PMID- 29566241
TI  - PUBLIC EXPOSURE TO MULTIPLE RF SOURCES IN GHANA.
AB  - This paper describes an effort to respond to the suggestion in World Health
      Organization (WHO) research agenda to better quantify potential exposure levels
      from a range of radiofrequency (RF) sources at 200 public access locations in
      Ghana. Wide-band measurements were performed-with a spectrum analyser and a log
      periodic antenna using three-point spatial averaging method. The overall results
      represented a maximum of 0.19% of the ICNIRP reference levels for public
      exposure. These results were generally lower than found in some previous but were
      58% (2.0 dB) greater, than found in similar work conducted in the USA. Major
      contributing sources of RF fields were identified to be FM broadcast and mobile
      base station sites. Three locations with the greatest measured RF fields could
      represent potential areas for epidemiological studies.

PMID- 29566242
TI  - Childhood Socioeconomic Status and Late-Adulthood Mental Health: Results from the
      Survey on Health, Ageing and Retirement in Europe.
AB  - Objectives: A growing literature acknowledges the association between childhood
      socioeconomic status (SES) and health in late adulthood (i.e., 50+). Less,
      however, is known about the association with mental health outcomes, such as
      depression. We use the Survey on Health, Ageing and Retirement in Europe (SHARE)
      to analyse overall and gender-specific associations between childhood SES and
      late-adulthood depression. Methods: Using life-history and contemporaneous data
      from 21,989 SHARE respondents in combination with principal component analysis we
      construct indices of childhood SES. We measure late-adulthood depression using
      the EURO-D scale. Contemporaneous SES is operationalized as the logarithm of
      household equivalised income. We estimate associations using linear regression
      models. Results: We document a positive association between childhood SES and the
      late-adulthood EURO-D score. The association persists even when allowing for
      contemporaneous SES. Zooming in on gender-specific associations reveals that the
      association for mental health is particularly pronounced for women. Discussion:
      Our findings reveal the long-term association between childhood socioeconomic
      conditions and depression later in life, which persists even after taking into
      account current socioeconomic conditions and are stronger for women than for men.
      These results imply that boosting childhood socioeconomic conditions can
      potentially have effects lasting well beyond the childhood phase.

PMID- 29566240
TI  - Identification of high affinity HER2 binding antibodies using CHO Fab surface
      display.
AB  - Discovery of monoclonal antibodies is most commonly performed using phage or
      yeast display but mammalian cells are used for production because of the complex
      antibody structure, including the multiple disulfide bonds and glycosylation,
      required for function. As this transition between host organisms is often
      accompanied by impaired binding, folding or expression, development pipelines
      include laborious plate-based screening or engineering strategies to adapt an
      antibody to mammalian expression. To circumvent these problems, we developed a
      plasmid-based Fab screening platform on Chinese hamster ovary (CHO) cells which
      allows for antibody selection in the production host and in the presence of the
      same post-translational modifications as the manufactured product. A hu4D5
      variant with low affinity for the human epidermal growth factor receptor (HER2)
      growth factor receptor was mutagenized and this library of ~106 unique clones was
      screened to identify variants with up to 400-fold enhanced HER2 binding. After
      two rounds of fluorescence activated cell sorting (FACS), four unique clones
      exhibited improved antigen binding when expressed on the CHO surface or as
      purified human IgG. Three of the four clones contained free cysteines in third
      complementarity determining region of the antibody heavy chain, which did not
      impair expression or cause aggregation. The improved clones had similar yields
      and stabilities as hu4D5 and similar sub-nanomolar affinities as measured by
      equilibrium binding to target cells. The limited size of mammalian libraries
      restricts the utility of this approach for naive antibody library screening, but
      it is a powerful approach for antibody affinity maturation or specificity
      enhancement and is readily generalizable to engineering other surface receptors,
      including T-cell receptors and chimeric antigen receptors.

PMID- 29566243
TI  - Overexpression of miR169o, an Overlapping MicroRNA in Response to Both Nitrogen
      Limitation and Bacterial Infection, Promotes Nitrogen Use Efficiency and
      Susceptibility to Bacterial Blight in Rice.
AB  - Limiting nitrogen (N) supply contributes to improved resistance to bacterial
      blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) in susceptible rice
      (Oryza sativa). To understand the regulatory roles of microRNAs (miRNAs) in this
      phenomenon, 63 differentially expressed overlapping miRNAs in response to Xoo
      infection and N limitation stress in rice were identified through deep RNA
      sequencing and stem-loop quantitative real-time PCR. Among these, miR169o was
      further assessed as a typical overlapping miRNA through the overexpression of the
      miR169o primary gene. Osa-miR169o-OX plants were taller, and had more biomass
      accumulation with significantly increased nitrate and total amino acid contents
      in roots than the wild type (WT). Transcript level assays showed that under
      different N supply conditions, miR169o oppositely regulated NRT2, and this is
      reduced under normal N supply conditions but remarkably induced under N-limiting
      stress. On the other hand, osa-miR169o-OX plants also displayed increased disease
      lesion lengths and reduced transcriptional levels of defense gene (PR1b, PR10a,
      PR10b and PAL) compared with the WT after inoculation with Xoo. In addition,
      miR169o impeded Xoo-mediated NRT transcription. Therefore, the overlapping
      miR169o contributes to increase N use efficiency and negatively regulates the
      resistance to BB in rice. Consistently, transient expression of NF-YA genes in
      rice protoplasts promoted the transcripts of PR genes and NRT2 genes, while it
      reduced the transcripts of NRT1 genes. Our results provide novel and additional
      insights into the co ordinated regulatory mechanisms of cross-talk between Xoo
      infection and N deficiency responses in rice.

PMID- 29566244
TI  - Activating Aging Stereotypes Increases Source Recollection Confusions in Older
      Adults: Effect at Encoding but Not Retrieval.
AB  - Objectives: Activating aging stereotypes can impair older adult performance on
      episodic memory tasks, an effect attributed to stereotype threat. Here, we report
      the first study comparing the effects of explicitly activating aging stereotypes
      at encoding versus retrieval on recollection accuracy in older adults. Method:
      During the encoding phase, older adults made semantic judgments about words, and
      during the retrieval phase, they had to recollect these judgments. To manipulate
      stereotype activation, participants read about aging-related decline (stereotype
      condition) or an aging-neutral passage (control condition), either before
      encoding or after encoding but before retrieval. We also assessed stereotype
      effects on metacognitive beliefs and two secondary tasks (working memory, general
      knowledge) administered after the recollection task. Results: Stereotype
      activation at encoding, but not retrieval, significantly increased recollection
      confusion scores compared to the control condition. Stereotype activation also
      increased self-reports of cognitive decline with aging, but it did not reliably
      impact task-related metacognitive assessments or accuracy on the secondary tasks.
      Discussion: Explicitly activating aging stereotypes at encoding increases the
      likelihood of false recollection in older adults, potentially by diminishing
      encoding processes. Stereotype activation also influenced global metacognitive
      assessments, but this effect may be unrelated to the effect of stereotypes on
      recollection accuracy.

PMID- 29566245
TI  - Hypercoagulability, Obstructive Sleep Apnea, and Pulmonary Embolism.

PMID- 29566246
TI  - Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients Coinfected With
      Hepatitis C Virus and Human Immunodeficiency Virus Type 1: The EXPEDITION-2
      Study.
AB  - Background: Once-daily glecaprevir coformulated with pibrentasvir
      (glecaprevir/pibrentasvir) demonstrated high rates of sustained virologic
      response 12 weeks after treatment (SVR12) in patients with hepatitis C virus
      (HCV) genotype 1-6 infection. This phase 3 study evaluated the efficacy and
      safety of glecaprevir/pibrentasvir in patients with chronic HCV genotype 1-6 and
      human immunodeficiency virus type 1 (HIV-1) coinfection, including patients with
      compensated cirrhosis. Methods: EXPEDITION-2 was a phase 3, multicenter, open
      label study evaluating glecaprevir/pibrentasvir (300 mg/120 mg) in HCV genotype 1
      6/HIV-1-coinfected adults without and with compensated cirrhosis for 8 and 12
      weeks, respectively. Patients were either HCV treatment-naive or experienced with
      sofosbuvir, ribavirin, or interferon, and antiretroviral therapy (ART) naive or
      on a stable ART regimen. Treatment-experienced genotype 3-infected patients were
      excluded. The primary endpoint was the SVR12 rate. Results: In total, 153
      patients were enrolled, including 16 (10%) with cirrhosis. The SVR12 rate was 98%
      (n = 150/153; 95% confidence interval, 95.8-100), with no virologic failures in
      137 patients treated for 8 weeks. One genotype 3-infected patient with cirrhosis
      had on-treatment virologic failure. Most adverse events were mild in severity; 4
      patients (2.6%) had serious adverse events, all deemed unrelated to
      glecaprevir/pibrentasvir. Treatment discontinuation was rare (<1%). All patients
      treated with ART maintained HIV-1 suppression (<200 copies/mL) during treatment.
      Conclusions: Glecaprevir/pibrentasvir for 8 weeks in noncirrhotic and 12 weeks in
      cirrhotic patients is a highly efficacious and well-tolerated treatment for
      HCV/HIV-1 coinfection, regardless of baseline HCV load or prior treatment with
      interferon or sofosbuvir. Clinical trial registration: NCT02738138.

PMID- 29566247
TI  - Increased polyamines as protective disease modifiers in congenital muscular
      dystrophy.
AB  - Most Mendelian disorders, including neuromuscular disorders, display extensive
      clinical heterogeneity that cannot be solely explained by primary genetic
      mutations. This phenotypic variability is largely attributed to the presence of
      disease modifiers, which can exacerbate or lessen the severity and progression of
      the disease. LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD) is a fatal
      degenerative muscle disease resulting from mutations in the LAMA2 gene encoding
      Laminin-alpha2. Progressive muscle weakness is predominantly observed in the
      lower limbs in LAMA2-CMD patients, whereas upper limbs muscles are significantly
      less affected. However, very little is known about the molecular mechanism
      underlying differential pathophysiology between specific muscle groups. Here, we
      demonstrate that the triceps muscles of the dy2j/dy2j mouse model of LAMA2-CMD
      demonstrate very mild myopathic findings compared with the tibialis anterior (TA)
      muscles that undergo severe atrophy and fibrosis, suggesting a protective
      mechanism in the upper limbs of these mice. Comparative gene expression analysis
      reveals that S-Adenosylmethionine decarboxylase (Amd1) and Spermine oxidase
      (Smox), two components of polyamine pathway metabolism, are downregulated in the
      TA but not in the triceps of dy2j/dy2j mice. As a consequence, the level of
      polyamine metabolites is significantly lower in the TA than triceps.
      Normalization of either Amd1 or Smox expression in dy2j/dy2j TA ameliorates
      muscle fibrosis, reduces overactive profibrotic TGF-beta pathway and leads to
      improved locomotion. In summary, we demonstrate that a deregulated polyamine
      metabolism is a characteristic feature of severely affected lower limb muscles in
      LAMA2-CMD. Targeted modulation of this pathway represents a novel therapeutic
      avenue for this devastating disease.

PMID- 29566248
TI  - Prevalence of sensitization to Aspergillus flavus in patients with allergic
      bronchopulmonary aspergillosis.
AB  - Aspergillus fumigatus is the most common Aspergillus species worldwide; however,
      A. flavus has also been shown to be prevalent in North India. Herein, we
      investigate the prevalence of sensitization to A. flavus in subjects with
      allergic bronchopulmonary aspergillosis (ABPA). We also evaluate the occurrence
      of allergic bronchopulmonary mycosis (ABPM) due to A. flavus. Treatment-naive
      subjects with ABPA underwent sputum culture; and, skin testing, fungal-specific
      immunoglobulin E (IgE) and serum precipitation tests for A. fumigatus and A.
      flavus. Sensitization to A. flavus was diagnosed if any immunological test for A.
      flavus was positive in subjects with ABPA. ABPM was labelled as probable if
      sputum cultures grew A. flavus and A. flavus-specific IgE was greater than A.
      fumigatus-specific IgE; and, possible if only A. flavus-specific IgE was greater
      than A. fumigatus-specific IgE. Fifty-three subjects with a mean (SD) age of 34.2
      (12.8) years were included. Sensitization to A. flavus was seen in 51 (96.2%)
      subjects, with overlap occurring in 49 (92.5%), 21 (39.6%), and 12 (22.6%)
      instances on fungal-specific IgE, skin prick test and precipitins, respectively.
      Sputum culture was positive in 18 (33.9%; A. flavus [n = 12], A. fumigatus [n =
      6]) subjects. ABPM due to A. flavus was diagnosed in 16 (30.2%) subjects (10
      probable, 6 possible). They were more likely to have high-attenuation mucus and a
      trend towards higher occurrence of sinusitis, compared to ABPA. We found a high
      occurrence of sensitization to A. flavus in subjects with ABPA. Subjects with A.
      flavus-related ABPM had a higher likelihood of high-attenuation mucus and
      probability of sinusitis. More studies are required to confirm this observation.

PMID- 29566249
TI  - Molecular characterization of Leishmania infantum isolates in municipalities of
      the state of Minas Gerais, Brazil.
AB  - Background: Little is known about the genetic diversity of Leishmania infantum
      isolates in the state of Minas Gerais, Brazil. Methods: Molecular
      characterization of hsp70, mpi and ITS1 was carried out for 29 isolates of L.
      infantum from the bone marrow of naturally infected dogs from the cities of
      Divinopolis, Para de Minas and Brumadinho, located in the central-west, central
      and central regions of the state of Minas Gerais, Brazil, respectively. Results:
      Analysis of the parasite nucleotide sequences demonstrated very high homogeneity
      of the studied samples. Conclusions: In the endemic regions studied, parasites
      are genotypically indistinguishable.

PMID- 29566250
TI  - Common Mistakes to Avoid When Reporting Quantitative Analyses and Results.

PMID- 29566251
TI  - The Role of Electrodiagnostic Studies in Carpal Tunnel Syndrome: Beyond
      Confirmation of Diagnosis.

PMID- 29566252
TI  - A Practicable and Systematic Approach to Medicolegal Causation.

PMID- 29566253
TI  - Percutaneous Osseointegrated Prostheses for Transfemoral Amputations.
AB  - The direct attachment of the osseointegrated prosthesis to the skeleton avoids
      the inherent problems of socket suspension. It also permits physiological weight
      bearing, improved range of motion in the proximal joint, and osseoperceptive
      sensor feedback, enabling better control of the artificial limb by amputees. This
      article describes the osseointegration program in Sweden based on the use of bone
      anchored prostheses for transfemoral amputation rehabilitation. The authors
      discuss in detail the patient-centered evaluation, surgical technique, and
      postoperative rehabilitation protocol. The outcomes of a prospective study of
      transfemoral amputees using the bone-anchored prostheses are presented.
      [Orthopedics. 2018; 41(2):75-80.].

PMID- 29566254
TI  - New insights into the pathophysiology of inflammatory bowel disease: microbiota,
      epigenetics and common signalling pathways.
AB  - The exact pathophysiology of inflammatory bowel disease (IBD) is still unknown.
      However, over the years important insights allowed the development of novel
      therapeutic approaches that are at the threshold of introduction into clinical
      practice, or at least in clinical trials. After being first described by Burrill
      B. Crohn, Crohn's disease, one of the two major forms of IBD, was perceived as an
      infectious disease. When the concept of autoimmune diseases was formulated,
      Crohn's disease and ulcerative colitis were thought to be members of this disease
      group. T cells certainly contribute to the chronification of the intestinal
      inflammation and targeting T cell migration has been introduced some years ago as
      a successful therapeutic approach in IBD. Despite the development of successful
      therapy based on this pathophysiological concept, IBD is no longer seen as a
      typical autoimmune disease. After the millennium, genome wide association studies
      on genetic variants and risk factors in these polygenetic diseases have told us a
      lot about pathogenetic pathways. However, genetic susceptibility explains only up
      to one third of the cases. Environmental factors also must play a role. Those
      environmental factors may "transfer" their disease-promoting potential into
      pathophysiological pathways with the intestinal microbiota as mediator. Hence,
      the intestinal microbiota has gained much attention as an important factor in
      disease development. Microbial factors, as well as other direct environmental
      influences, have been shown to affect epigenetic signatures, intestinal
      epithelial cells and the innate immune system, providing another important
      concept on how these diseases originate and can cause repeated flares at the same
      gut segments even after years of remission and after intermediate complete
      mucosal healing. Current pathophysiological concepts of IBD not only help us to
      better understand these diseases and develop new therapies. They also illustrate
      the evolution of basic scientific concepts over time and that sometimes partially
      or even largely abandoned concepts persistently influence out current
      thinking/clinical practice.

PMID- 29566255
TI  - The bZip transcription factor HY5 mediates CRY1a-induced anthocyanin biosynthesis
      in tomato.
AB  - The production of anthocyanin is regulated by light and corresponding
      photoreceptors. In this study, we found that exposure to blue light and
      overexpression of CRY1a are associated with increased accumulation of anthocyanin
      in tomato (Solanum lycopersicum L.). These responses are the result of changes in
      mRNA and the protein levels of SlHY5, which is a transcription factor. In vitro
      and in vivo experiments using electrophoretic mobility shift assay and ChIP-qPCR
      assays revealed that SlHY5 could directly recognize and bind to the G-box and
      ACGT-containing element in the promoters of anthocyanin biosynthesis genes, such
      as chalcone synthase 1, chalcone synthase 2, and dihydroflavonol 4-reductase.
      Silencing of SlHY5 in OE-CRY1a lines decreased the accumulation of anthocyanin.
      The findings presented here not only deepened our understanding of how light
      controls anthocyanin biosynthesis and associated photoprotection in tomato
      leaves, but also allowed us to explore potential targets for improving pigment
      production.

PMID- 29566256
TI  - Caregivers experiences of nursing care for relatives hospitalized during manic
      episode: A phenomenological study.
AB  - PURPOSE: To describe the experiences of informal caregivers with the nursing care
      received by relatives hospitalized for mania. DESIGN AND METHODS: Multicenter
      phenomenological study using open interviews. Data were analyzed using the
      Stevick-Colaizzi-Keen method. FINDINGS: The essence of the experiences was the
      importance of communication, about being informed and involved in treatment
      during hospitalization of their relative. The experiences depended on the nature
      of the relation between participant and relative. PRACTICE IMPLICATIONS: Nurses
      should listen to caregivers' experiences, inquire about the expectations of
      caregivers regarding nursing care, and advise informal caregivers on how to take
      care of their relatives.

PMID- 29566257
TI  - Seven additional families with spondylocarpotarsal synostosis syndrome with novel
      biallelic deleterious variants in FLNB.
AB  - The location and/or type of variants in FLNB result in a spectrum of
      osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal
      synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such
      as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal
      synostosis syndrome is characterized by disproportionate short stature, vertebral
      anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function
      variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9
      families and 9 pathogenic variants have been reported so far. We report clinical
      features of 10 additional patients from 7 families with spondylocarpotarsal
      synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding
      the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome.
      Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal
      coalition) and molecular (truncating variants in FLNB) characteristics of this
      condition.

PMID- 29566258
TI  - Loose anagen hair syndrome: Treatment with systemic minoxidil characterised by
      marked hair colour change.

PMID- 29566259
TI  - Is there a common experience? Somali new mothers' childbirth experiences in
      Norway and the United States.
AB  - BACKGROUND: Due to civil war, Somalis immigrants have settled in Norway and the
      United States. Large families are valued among Somalis and Somali women continue
      to give birth in their new countries. Research studies have been conducted with
      Somali immigrant new mothers in Norway and Minnesota, United States to understand
      perceptions of their childbirth experience. PURPOSE: The purpose of this
      qualitative study was to compare the childbirth experiences of Somali immigrant
      mothers in the United States and Norway to make recommendations to improve health
      care practice. DESIGN: This paper presents a comparison of two research studies
      in order to identify and explain similarities and differences between cross
      cultural immigrant populations. RESULTS: Both studies identified themes related
      to the importance of family support in the postpartum period, fear of Cesarean
      delivery, and relationships with nurses. These studies give recommendations for
      nurses on how to provide culturally sensitive care for Somali new mothers.
      CONCLUSIONS: Implications for practice are that nurses should develop trusting
      relationships with Somali mothers and facilitate cultural and religious
      practices. Information regarding support resources in the community should be
      provided to Somali mothers throughout the perinatal period.

PMID- 29566260
TI  - Ixekizumab-treatment-emergent photosensitive cutaneous eruption.

PMID- 29566261
TI  - Effects of trimethoprim-sulfadiazine and detomidine on the function of equine Kv
      11.1 channels in a two-electrode voltage-clamp (TEVC) oocyte model.
AB  - The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia
      and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction
      between drugs and potassium channels, especially the Kv 11.1 channel. Due to such
      interactions, numerous drugs have been withdrawn from the market or are
      administered with precautions in human medicine. However, some compounds, such as
      trimethoprim-sulfonamide combinations are still widely used in veterinarian
      medicine. Therefore, we investigate the effect of trimethoprim-sulfadiazine
      (TMS), trimethoprim, sulfadiazine, and detomidine on equine-specific Kv 11.1
      channels. Kv 11.1 channels cloned from equine hearts were heterologously
      expressed in Xenopus laevis oocytes, and whole cell currents were measured by two
      electrode voltage-clamp before and after drug application. TMS blocked equine Kv
      11.1 current with an IC50 of 3.74 mm (95% CI: 2.95-4.73 mm) and affected the
      kinetics of activation and inactivation. Similar was found for trimethoprim but
      not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine
      did not affect equine Kv 11.1 current. Thus, equine Kv 11.1 channels are also
      susceptible to pharmacological block, indicating that some drugs may have the
      potential to affect repolarization in horse. However, in vivo studies are needed
      to assess the potential risk of these drugs to induce equine LQTS.

PMID- 29566262
TI  - Regulatory T cells: a potential target in cancer immunotherapy.
AB  - Cancer immunotherapy involving blockade of immune checkpoint molecules, such as
      CTLA-4 and PD-1, has shown remarkable clinical success across several types of
      malignancies. However, a fraction of patients experience disease progression
      after treatment; thus, exploring resistant mechanisms for immune checkpoint
      inhibitors and improving their treatment outcome with additional modalities are
      of great importance. CD4+ regulatory T (Treg ) cells characterized by expression
      of the master regulatory transcription factor FOXP3 are a highly immune
      suppressive subset of CD4+ T cells that maintain immune homeostasis. Several
      preclinical and clinical studies suggest that Treg cells hamper immune
      surveillance against cancer in healthy individuals, prevent the development of
      effective antitumor immunity in tumor-bearing patients, and promote tumor
      progression. Therefore, targeting Treg cells should be crucial to improving the
      treatment outcomes of cancer immunotherapy. Several clinical studies directly or
      indirectly targeting Treg cells in combination with immune checkpoint inhibitors
      are ongoing or being planned. Understanding the characteristics and roles of Treg
      cells in cancer settings could make disease-specific Treg -targeted therapy more
      efficacious and reduce the incidence of immune-related adverse effects mediated
      by Treg cell inhibition.

PMID- 29566263
TI  - Comparison of vesical pressure values achieved by Valsalva maneuvers: A
      standardization proposal.
AB  - AIMS: To perform a comparative evaluation of Valsalva maneuver techniques, in an
      attempt to identify the most suitable one for achieving leak point pressure (LPP)
      during the cystometric phase of the urodynamic study (UDS), in order to propose a
      method for technical standardization. METHODS: Urodynamic data from women with
      stress urinary incontinence at three urogynecological medical centers were
      randomly selected and prospectively analyzed. Valsalva maneuver was executed
      through forceful attempted exhalation against the dorsal surface of the hand
      (Group 1), through abdominal strain (Group 2), or through low-elasticity latex
      balloon-blowing (Group 3). Patients were classified based on age and higher
      vesical pressure value, as well as time to perform Valsalva maneuver. RESULTS:
      Initially, 1358 urodynamic studies were identified as eligible for analysis.
      Among these, 340 belonged to Group 1, 318 to Group 2, and 700 to Group 3.
      Valsalva maneuver accomplished through abdominal straining was more effective,
      inducing increased vesical pressure, across age groups. The same maneuver may be
      sustained for longer than the other two techniques. CONCLUSION: When performed
      through abdominal strain, the Valsalva maneuver was more effective for stress
      urinary incontinence urodynamic's investigation.

PMID- 29566264
TI  - The effects of cystoscopy and hydrodistention on symptoms and bladder capacity in
      interstitial cystitis/bladder pain syndrome.
AB  - AIMS: The use of cystoscopy and hydrodistention in the management of interstitial
      cystitis/bladder pain syndrome (IC/BPS) varies widely between providers. Current
      evidence regarding the risks and benefits of hydrodistention, as well as the long
      term effects of repeated hydrodistention are not well established. We sought to
      characterize the effects of hydrodistention on IC/BPS symptoms as well as bladder
      capacity. METHODS: We retrospectively queried our institutional records for
      patients with non-ulcerative IC/BPS who underwent hydrodistention over an 11-year
      period to obtain demographic and clinical factors at the time of diagnosis and
      treatment. Symptom relief and bladder capacity changes were assessed, and
      multivariable models were used to predict response to treatment. RESULTS: There
      were 328 patients who underwent hydrodistention during the study period, of whom
      36% received the procedure multiple times, and overall median follow-up was 38.6
      months. Patients with repeated hydrodistentions were more likely to be female,
      have more comorbid pain disorders, and have trialed anticholinergic medications
      and intravesical instillations. No decrease in mean bladder capacity was observed
      over time (P = 0.40). Significant decreases in symptom scores were observed
      following the procedure on multiple questionnaires. CONCLUSIONS: Hydrodistention
      does not decrease bladder capacity even with multiple procedures, and measurably
      improves symptoms in some patients with IC/BPS. Continuing efforts to better
      identify those patients most likely to benefit from this procedure are justified.

PMID- 29566265
TI  - Long-term functional outcome analysis in a large cohort of patients after radical
      prostatectomy.
AB  - INTRODUCTION: Goal of the study was an analysis of functional outcomes after
      radical prostatectomy (RP) in a large cohort of patients. METHODS: Functional
      outcomes were assessed with the ICIQ-SF questionnaire and daily pad-usage for the
      evaluation of stress urinary incontinence (SUI) as well as with the IIEF-5 score
      for the evaluation of erectile dysfunction (ED). Statistical analysis included
      log-rank test, Mann-Whitney-Test, ANOVA test and logistic regression (P < 0.05).
      RESULTS: In total 4003 patients were included in the study. Median follow-up was
      42 months (min. 2-max. 147 mo.). Regarding ED, an IIEF-5 score of >=20 was
      reached by 39% of patients. Regarding SUI, 55% stated that they needed no pads,
      21% of patients needed one pad per day. 33% of patients reported of no
      incontinence (0 p. in ICIQ), 26% of patients reported of a mild incontinence (1-5
      p. in ICIQ). Patients global impression of their overall health respectively
      patients subjective quality of life were assessed with the EORTC QLC-C30 and were
      both high with a median of six points (on a scale of 1-7). In multivariate
      analysis time since surgery could be identified as independent risk factors on
      QOL (P = 0.0028), IIEF-5 (P = 0.0149), ICIQ (P < 0.001), and pads per day (P <
      0.001). CONCLUSIONS: Our data show a good continence status, a clearly impaired
      erectile function but overall a good quality of life after surgery. In summary
      older patients-with an advanced tumor and adjuvant radiation therapy-were at
      highest risk for an impaired functional outcome.

PMID- 29566266
TI  - A Computational Model of the Self-Teaching Hypothesis Based on the Dual-Route
      Cascaded Model of Reading.
AB  - The self-teaching hypothesis describes how children progress toward skilled sight
      word reading. It proposes that children do this via phonological recoding with
      assistance from contextual cues, to identify the target pronunciation for a novel
      letter string, and in so doing create an opportunity to self-teach new
      orthographic knowledge. We present a new computational implementation of self
      teaching within the dual-route cascaded (DRC) model of reading aloud, and we
      explore how decoding and contextual cues can work together to enable accurate
      self-teaching under a variety of circumstances. The new model (ST-DRC) uses DRC's
      sublexical route and the interactivity between the lexical and sublexical routes
      to simulate phonological recoding. Known spoken words are activated in response
      to novel printed words, triggering an opportunity for orthographic learning,
      which is the basis for skilled sight-word reading. ST-DRC also includes new
      computational mechanisms for simulating how contextual information aids word
      identification, and it demonstrates how partial decoding and ambiguous context
      interact to achieve irregular-word learning. Beyond modeling orthographic
      learning and self-teaching, ST-DRC's performance suggests new avenues for
      empirical research on how difficult word classes such as homographs and
      potentiophones are learned.

PMID- 29566267
TI  - Tadalafil attenuates hypotonicity-induced Ca2+ influx via TRPV2 and TRPV4 in
      primary rat bladder urothelial cell cultures.
AB  - AIMS: To investigate the localization of phosphodiesterase 5 (PDE5) and the
      molecular mechanism underlying the effect of the PDE5 inhibitor tadalafil in
      signal transduction in the bladder urothelium. METHODS: PDE5 expression in rat
      bladder tissues and cultured primary rat bladder urothelial cells was evaluated
      using immunochemistry and western blot assays. Ca2+ influx in cells exposed to
      isotonic solution, hypotonic solution, a selective transient receptor potential
      vanilloid 2 (TRPV2) channel agonist (cannabidiol), a selective TRPV4 channel
      agonist (GSK1016790A), a TRP cation channel melastatin 7 (TRPM7) channel agonist
      (PIP2), or a purinergic receptor agonist (ATP) in the presence or absence of 10
      uM tadalafil was evaluated using calcium imaging techniques. We also evaluated
      stretch-induced changes in ATP concentration in the mouse bladder in the presence
      or absence of 100 uM tadalafil. RESULTS: Immunochemistry and western blot
      analyses demonstrated that PDE5 is abundantly expressed in the bladder urothelium
      and in primary rat urothelial cells. Ca2+ influx induced by hypotonic
      stimulation, GSK1016790A, or cannabidiol was significantly inhibited by
      tadalafil, whereas ATP-induced Ca2+ influx was unaffected by tadalafil. PIP2 did
      not induce Ca2+ influx. ATP release in tadalafil-pretreated bladders
      significantly decreased compared to control bladders. CONCLUSIONS: Tadalafil
      attenuates Ca2+ influx via TRPV4 and TRPV2, and inhibits ATP release in the
      bladder urothelium. These findings indicate that tadalafil functions as an
      inhibitor of urothelial signal transduction.

PMID- 29566268
TI  - Nonfluoroscopic catheter ablation of paroxysmal atrial fibrillation.
AB  - AIMS: Radiofrequency catheter ablation of atrial fibrillation (AF) is one of the
      most complex ablation procedures. Both patients and operators are exposed to
      scattered radiation. This study evaluated the safety and efficacy of intracardiac
      echo (ICE)-guided pulmonary vein isolation (PVI) without fluoroscopy. METHODS: We
      retrospectively analyzed the data of 481 consecutive patients with paroxysmal AF
      undergoing radiofrequency PVI with the CARTO 3 system (Biosense Webster, Diamond
      Bar, CA, USA). ICE-guided PVI without fluoroscopy and without CT/MRI integration
      (Nonfluoro group) was performed for 245 patients, and conventional fluoroscopy
      guided PVI (Fluoro group) was performed for 236 patients. The primary safety
      endpoint was the incidence of major adverse events. The primary efficacy endpoint
      was freedom from AF during follow-up. Secondary endpoints included procedure
      duration, fluoroscopy duration, and acute PVI rate. RESULTS: Mean procedure times
      between groups were similar (108.8 +/- 18.2 minutes in the Non-fluoro group vs
      113.6 +/- 26.8 minutes in the Fluoro group; P  =  not significant [NS]). Acute
      PVI was achieved in all patients, with mean radiofrequency application times of
      43.4 +/- 7.5 and 44.4 +/- 10.7 minutes for the Nonfluoro and Fluoro groups,
      respectively (P  =  NS). The incidence of cardiac tamponade was 1.2% (3/245
      patients) in the Nonfluoro group and 0.8% (2/236 patients) in the Fluoro group (P
      =  NS). During 15.2 +/- 4.1 months of follow-up, after a single procedure, AF
      recurrence was documented in 65 of 245 (26.5%) patients and 61 of 236 (25.8%)
      patients in the Nonfluoro and Fluoro groups, respectively (P  =  NS).
      CONCLUSIONS: Nonfluoroscopic ICE-guided catheter ablation of AF without prior
      cardiac image integration or angiography is feasible and safe. PVI without
      fluoroscopy did not affect procedure duration or long-term efficacy.

PMID- 29566269
TI  - Development of the Impact of Nighttime Urination (INTU) questionnaire to assess
      the impact of nocturia on health and functioning.
AB  - AIMS: This study describes development of the Impact of Nighttime Urination
      (INTU) questionnaire to assess nocturia impacts on health and functioning.
      METHODS: Development of the questionnaire followed an iterative patient-directed
      process as recommended by current guidance for patient-reported outcome (PRO)
      measures. An initial 15-item questionnaire was devised based on reviewing the
      published literature, and then modified through four rounds of semi-structured
      interviews of 28 individuals with nocturia. In each round, open-ended concept
      elicitation, followed by cognitive debriefing, was used to assess the
      questionnaire. Items were modified based on participants' responses and
      incorporated into the next round of interviews. RESULTS: In all rounds,
      participants reported that their experiences were easy to recall and report on a
      daily basis and that the burden of completing the questionnaire was low. The
      final questionnaire has a same-day recall period. It includes six daytime impact
      items-having limited concentration, a sense of feeling tired, difficulty getting
      things done, irritability, not feeling rested, and drowsiness-and four items that
      measure the nighttime impact of nocturia-patient concern, waking up too early,
      difficulty getting enough sleep, and feeling bothered by having to get up at
      night to void. Responses follow a 5- or 4-point scale. The final INTU captures
      the key concepts associated with nocturia as confirmed by cognitive debriefing.
      CONCLUSIONS: Development of the 10-item INTU, a nocturia-specific PRO measure,
      was based on direct input and feedback from patients and has demonstrated that it
      captures the patient-reported impacts of nocturia.

PMID- 29566270
TI  - A customized approach for arm fat reduction using cryolipolysis.
AB  - OBJECTIVES: Cryolipolysis of the arms has been demonstrated to be an effective
      treatment for non-invasive reduction of subcutaneous fat. This study evaluated
      the safety and efficacy of the concurrent use of a new commercially-available
      small applicator in conjunction with an existing medium sized applicator for the
      customized treatment of arm fat. METHODS: Bilateral arms of 15 eligible subjects
      were simultaneously treated using one or two vacuum applicators with flat
      contours. Either a medium or small cryolipolysis applicator with an oblong cup
      shaped cooling surface was selected to treat upper arm fat. The shape of the fat
      bulge in each subject's arm was assessed and up to two treatment cycles (-11
      degrees C for 35 minutes each) were delivered to each arm in one session, based
      upon investigator discretion. Throughout the procedure and at the completion of
      each treatment cycle, investigators assessed the subject's level of comfort, as
      well as sensory and motor nerve effects. Post-treatment manual massage was
      performed, and clinical assessments of each treatment site were recorded. Adverse
      events were recorded to monitor procedural safety. Baseline and 12 weeks post
      treatment photographs and ultrasound measurements were taken to assess efficacy.
      Subject questionnaires were administered to evaluate satisfaction. RESULTS:
      Fifteen female subjects (mean age of 51.1, mean BMI of 26.8) completed the study.
      Ultrasound imaging revealed statistically significant fat layer reduction of 2.5
      mm (SD +/- 2.4 mm, 95%CI 1.6-3.3). Subject surveys administered 12 weeks post
      treatment demonstrated 87% satisfaction with the arm cryolipolysis procedure. A
      panel of blinded, independent physicians correctly identified 83% of the before
      and after photos. Clinical assessments found adverse events were mild and
      included erythema and mild swelling that resolved without intervention. Mild
      treatment area numbness was reported by 73% of subjects at the 4-week interim
      visit and fully resolved at the 12-week visit. CONCLUSION: This study documents
      the first reported customized approach for assessment and treatment of arm fat
      using a small or medium cup applicator with varied applicator placement. By
      incorporating one or two treatment cycles per arm in a single session, the issue
      of variable fat distribution in people's arms can be addressed. This approach was
      shown to be a safe and effective way to reduce unwanted arm fat with high patient
      satisfaction. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 29566271
TI  - Lessons learned from using an audience response system in a community setting for
      research data collection.
AB  - OBJECTIVES: A community-academic team implemented a study involving collection of
      quantitative data using a computer-based audience response system (ARS) whereby
      community partners led data collection efforts. The team participated in a
      reflection exercise after the data collection to evaluate and identify best
      practices and lessons learned about the community partner-led process. DESIGN &
      SAMPLE: The methods involved a qualitative research consultant who facilitated
      the reflection exercise that consisted of two focus groups-one academic and one
      community research team members. The consultant then conducted content analysis.
      Nine members participated in the focus groups. RESULTS: The reflection identified
      the following themes: the positive aspects of the ARS; challenges to overcome;
      and recommendations for the future. CONCLUSION: The lessons learned here can help
      community-academic research partnerships identify the best circumstances in which
      to use ARS for data collection and practical steps to aid in its success.

PMID- 29566272
TI  - Association between lifetime risk of atrial fibrillation and mortality in the
      oldest old.
AB  - BACKGROUND: Age is the strongest predictor of atrial fibrillation (AF), yet
      little is known about AF incidence in the oldest old. HYPOTHESIS: AF incidence
      declines after age 90 years, and morbidity is compressed into a brief period at
      the end of life. METHODS: In this retrospective, longitudinal cohort study of
      patients (born 1905-1935), we examined cumulative lifetime incidence of AF and
      its impact on mortality. Data included records from 1 062 610 octogenarians, 317
      161 nonagenarians, and 3572 centenarians. Kaplan-Meier curves were used to
      estimate cumulative incidence of AF by age group, incidence rates were compared
      using log-rank tests, and Cox proportional hazards model was used to estimate
      unadjusted hazard ratios. The primary outcome was AF incidence at age > 80 years;
      the secondary outcome was mortality. RESULTS: The cumulative AF incidence rate
      was 5.0% in octogenarians, 5.4% in nonagenarians, and 2.3% in centenarians.
      Octogenarians and nonagenarians had a higher risk of AF incidence compared to
      centenarians (adjusted hazard ratio 8.74, 95% confidence interval [CI]: 6.31
      12.04; and 2.98, 95% CI: 2.17-4.1, respectively). The lowest hazard ratio for
      mortality in patients with AF compared to those without was 2.3 (95% CI: 2.3-2.4)
      in patients who were on antiplatelet and anticoagulant medication and had a score
      of 0 on the Elixhauser comorbidity index score. CONCLUSIONS: Although AF
      incidence increased with age, being a centenarian was associated with reduced
      incidence and compression of morbidity. Patients with AF had a higher adjusted
      mortality rate. However, data suggest that a regimen of anticoagulants and
      antiplatelets may reduce risk of mortality in patients over 80 with an AF
      diagnosis.

PMID- 29566273
TI  - Appropriate use criteria in dermatopathology: Initial recommendations from the
      American Society of Dermatopathology.
AB  - BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test
      selection, and can affect health care delivery, reimbursement policy and
      physician decision-making. OBJECTIVES: The American Society of Dermatopathology,
      with input from the American Academy of Dermatology and the College of American
      Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA
      appropriateness methodology, which combines evidence-based medicine, clinical
      experience and expert judgment, was used to develop AUC in dermatopathology.
      RESULTS: With the number of ratings predetermined at 3, AUC were developed for
      211 clinical scenarios involving 12 ancillary studies. Consensus was reached for
      188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52
      (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness." LIMITATIONS:
      The methodology requires a focus on appropriateness without comparison between
      tests and irrespective of cost. CONCLUSIONS: The ultimate decision of when to
      order specific test rests with the physician and is one where the expected
      benefit exceeds the negative consequences. This publication outlines the
      recommendations of appropriateness-AUC for 12 tests used in dermatopathology.
      Importantly, these recommendations may change considering new evidence. Results
      deemed "uncertain appropriateness" and where consensus was not reached may
      benefit from further research.

PMID- 29566274
TI  - In silico characterization of broad range proteases produced by Serratia
      marcescens EGD-HP20.
AB  - In the present study, Serratia marcescens EGD-HP20 strain was demonstrated to
      utilize poultry waste comprising of both white non-melanized and dark/brown
      melanized poultry feathers. The potential of the isolate to hydrolyze diverse
      keratinous wastes was further corroborated by comparative genomics which
      indicated the presence of genes for broad substrate specific proteases including
      metallo-proteases, serine endoprotease, dipeptidase, oligopeptidase, etc.
      Multiple gene sequence alignments of above genes showed 99-100% sequence
      identities with that of closely related strains of S. marcescens. The secondary
      structure, 3D structures and energy models suggested the stable nature of all the
      observed enzymes. Comparative genomics and hydrolysis of mixed feather waste
      indicated that the above potential of the isolate was associated with synergistic
      action of various types of proteases.

PMID- 29566275
TI  - Acoustic variation of spider monkeys' contact calls (whinnies) is related to
      distance between vocalizing individuals and immediate caller behavior.
AB  - Due to several factors such as ecological conditions, group size, and social
      organization, primates frequently spend time out of visual contact with
      individuals of their own group. Through the use of long-distance vocalizations,
      often termed "contact calls," primates are able to maintain contact with out-of
      sight individuals. Contact calls have been shown to be individually distinct, and
      reverberation and attenuation provide information about caller distance. It is
      less clear, however, whether callers actively change the structure of contact
      calls depending on the distance to the presumed listeners. We studied this
      question in spider monkeys (Ateles geoffroyi), a species with complex spatial
      dynamics (fission-fusion society) that produces highly frequency modulated
      contact calls, denominated "whinnies." We determined the acoustic characteristics
      of 566 whinnies recorded from 35 free-ranging spider monkeys that belong to a
      community located in Mexico, and used cluster analyses, discriminant function
      analyses, and generalized linear mixed models to assess if they varied in
      relation to the presumed distance to the listener. Whinnies could be grouped into
      five subtypes. Since the lowest frequency subtype was mainly produced by spider
      monkeys that exchanged whinnies at longer distances, and lower frequency calls
      propagate across longer distances, our results suggest that whinnies vary in
      order to enhance vocal contact between individuals separated by different
      distances. Our results also revealed that whinnies convey potential information
      about caller immediate behaviors and corroborated that these calls are
      individually distinct. Overall, our results suggest that whinny acoustic
      variation facilitates the maintenance of vocal contact between individuals living
      in a society with complex spatial dynamics.

PMID- 29566276
TI  - Angiographic optical coherence tomography imaging of hemangiomas and port wine
      birthmarks.
AB  - OBJECTIVES: A current therapeutic challenge of vascular lesions is that they do
      not always respond effectively to laser treatment. Information on targeted
      vessels could potentially be used to guide laser treatments. Optical coherence
      tomography (OCT) is a useful tool for the non-invasive imaging of tissues,
      including skin hemangiomas and port wine birthmarks. Dynamic OCT is able to
      rapidly characterize cutaneous blood vessels. The primary goal of this study was
      to demonstrate the ability of bedside OCT to image (i) overall vessel pattern;
      (ii) individual vessel morphology, diameter and depth; and (iii) total vessel
      density as a function of depth in infantile hemangiomas and port wine birthmarks
      (PWB). MATERIALS AND METHODS: This IRB approved, observational clinical trial was
      performed among healthy volunteers ages 3 months-73 years old. All patients
      presented for laser treatment of either infantile hemangiomas or PWB with skin
      types ranging from Fitzpatrick I-V. OCT imaging of 49 hemangioma and PWB scans
      were performed pre- and post-treatment. The diameter and depth of the blood
      vessels making up the vascular lesions were measured. In addition, normal skin
      was scanned for comparison. Five datasets for infantile hemangiomas and five for
      PWB that were without motion artifacts were analyzed. RESULTS: Scanned lesions
      exhibited variable and highly heterogeneous blood vessel patterns with vessel
      diameters ranging from 20 to 160 MUm, suggesting that the laser treatment with
      single pulse durations may not be optimal. The largest blood vessel diameter
      observed (160 MUm) may not be adequately treated by commonly used pulsed dye
      laser pulse durations. CONCLUSION: OCT allowed rapid, non-invasive
      characterization of the diameter and depth of blood vessels in individual
      vascular lesions. Imaged lesions consisted of a heterogeneous population of
      vessel sizes, morphologies, and depth. Future studies could utilize this
      information to assist development of individualized treatment protocols in an
      effort to improve vascular birthmark removal. Lasers Surg. Med. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29566277
TI  - Stimulation of Fas/FasL-mediated apoptosis by luteolin through enhancement of
      histone H3 acetylation and c-Jun activation in HL-60 leukemia cells.
AB  - Luteolin (3',4',5,7-tetrahydroxyflavone), which exists in fruits, vegetables, and
      medicinal herbs, is used in Chinese traditional medicine for treating various
      diseases, such as hypertension, inflammatory disorders, and cancer. However, the
      gene-regulatory role of luteolin in cancer prevention and therapy has not been
      clarified. Herein, we demonstrated that treatment with luteolin resulted in a
      significant decrease in the viability of human leukemia cells. In the present
      study, by evaluating fragmentation of DNA and poly (ADP-ribose) polymerase
      (PARP), we found that luteolin was able to induce PARP cleavage and nuclear
      fragmentation as well as an increase in the sub-G0 /G1 fraction. In addition,
      luteolin also induced Fas and Fas ligand (FasL) expressions and subsequent
      activation of caspases-8 and -3, which can trigger the extrinsic apoptosis
      pathway, while knocking down Fas-associated protein with death domain (FADD)
      prevented luteolin-induced PARP cleavage. Immunoblot and chromatin
      immunoprecipitation (ChIP) analyses revealed that luteolin increased acetylation
      of histone H3, which is involved in the upregulation of Fas and FasL. Moreover,
      both the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase
      (JNK) pathways are involved in luteolin-induced histone H3 acetylation. Finally,
      luteolin also activated the c-Jun signaling pathway, which contributes to FasL,
      but not Fas, gene expression and downregulation of c-Jun expression by small
      interfering RNA transfection which resulted in a significant decrease in luteolin
      induced PARP cleavage. Thus, our results demonstrate that luteolin induced
      apoptosis of HL-60 cells, and this was associated with c-Jun activation and
      histone H3 acetylation-mediated Fas/FasL expressions.

PMID- 29566278
TI  - Down-regulation of POTEG predicts poor prognosis in esophageal squamous cell
      carcinoma patients.
AB  - POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE
      family is composed of many proteins which are very closely related and expressed
      in prostate, ovary, testis, and placenta. Some POTE paralogs are related with
      some cancers. Here we showed that down-regulation of POTEG was detected in about
      60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical
      association studies determined that POTEG down-regulation was significantly
      correlated with tumor differentiation, lymph nodes metastasis and TNM staging.
      Kaplan-Meier analysis determined that POTEG down-regulation was associated with
      poorer clinical outcomes of ESCC patients (P = 0.026). Functional studies showed
      that POTEG overexpression could suppress tumor cell growth and metastasis
      capacity in vitro and in vivo. Molecular analyses revealed that POTEG
      downregulated CDKs, leading to subsequent inhibition of Rb phosphorylation, and
      consequently arrested Cell Cycle at G1/S Checkpoint. POTEG overexpression induced
      apoptosis by activating caspases and PARP, and regulating canonical mitochondrial
      apoptotic pathways. On the other side, POTEG inhibited epithelial-mesenchymal
      transition and suppressed tumor cell metastasis. In conclusion, our study reveals
      a functionally important control mechanism of POTEG in esophageal cancer
      pathogenesis, suggesting potential use in the ESCC intervention and therapeutic
      strategies.

PMID- 29566279
TI  - Recurrent transcriptional loss of the PCDH17 tumor suppressor in laryngeal
      squamous cell carcinoma is partially mediated by aberrant promoter DNA
      methylation.
AB  - Protocadherins are cell-cell adhesion molecules encoded by a large family of
      genes. Recent reports demonstrate recurrent silencing of protocadherin genes in
      tumors and provide strong arguments for their tumor supresor functionality. Loss
      of protocadherins may contribute to cancer development not only by altering cell
      cell adhesion, that is a hallmark of cancer, but also by enhancing proliferation
      and epithelial mesenchymal transition of cells via deregulation of the WNT
      signaling pathway. In this study we have further corroborated our previous
      findings on the involvement of PCDH17 in laryngeal squamous cell carcinoma
      (LSCC). We used bisulfite pyrosequencing to analyze a cohort of primary LSCC
      tumors for alterations in PCDH17 promoter DNA methylation as an alternative gene
      inactivation mechanism to the homozygous deletions reported earlier. Moreover, we
      analyzed primary LSCC samples by immunohistochemistry for PCDH17 protein loss. We
      identified recurrent elevation of PCDH17 promoter DNA methylation in 32/81 (40%)
      primary tumors (P < 0.001) and therein hypermethylation of 12 (15%) cases in
      contrast to no tumor controls (n = 24) that were all unmethylated. Importantly,
      DNA demethylation by decitabine has restored low level PCDH17 expression in LSCC
      cell lines. In conclusion, we provide a mechanistic explanation of recurrently
      observed PCDH17 silencing in LSCC by demonstrating the role of promoter
      methylation in this process. In light of these findings and recent reports
      showing that PCDH17 methylation is detectable in serum of cancer patients we
      suggest that testing PCDH17 DNA methylation might serve as a potential biomarker
      in LSCC.

PMID- 29566280
TI  - Telescoping Reactions with Trifluorodiazoethane-Derived Aza-Wittig Reagents and
      Allenyl esters.
AB  - A telescoping process involving the consecutive addition of four reagents
      (trifluorodiazoethane, phosphine, allenyl ester, and acetic acid) into a single
      reactor was developed for the novel functionalization of allenyl esters. First,
      new phosphazenes derived from trifluorodiazoethane and phosphines were generated
      and reacted with allenyl esters to give unexpected alpha-iminophosphoranes
      through the creation of C=P, C=N, and C-H bonds at the alpha-, beta-, and gamma
      carbon atoms, respectively, of the allenyl esters. The alpha-iminophosphoranes
      did not react with aldehydes in a classic Wittig reaction, but instead beta
      enamino esters were obtained. The overall sequence of reactions offered a formal
      hydrohydrazonation of allenyl esters. The method was extended to other related
      diazo compounds and applied to the preparation of novel 5-pyrazolone derivatives.
      Not only is the telescoping process described herein an effective approach for
      truncating the multistep synthesis, but also each step has been dissected to
      understand and support the reaction mechanisms.

PMID- 29566281
TI  - Downregulation of miR-3127-5p promotes epithelial-mesenchymal transition via FZD4
      regulation of Wnt/beta-catenin signaling in non-small-cell lung cancer.
AB  - MiR-3127-5p has been implicated as a tumor-suppressive microRNA (miRNA) in non
      small-cell lung cancer (NSCLC) and its expression was associated with tumor
      recurrence and poor prognosis. The aim of this study was to determine whether miR
      3127-5p regulates epithelial-mesenchymal transition (EMT) in NSCLC, and to
      investigate the underlying mechanisms. Using qRT-PCR, we examined the expression
      levels of miR-3127-5p in a cohort of primary NSCLC specimens with and without
      distant metastasis. We further performed a series of in vitro and in vivo
      experiments to investigate the effects and underlying mechanism of miR-3127-5p on
      EMT, cell migration, invasion, and adhesion in NSCLC. We found that metastatic
      NSCLC tissues showed markedly downregulated miR-3127-5p expression. Transforming
      growth factor-beta1 (TGF-beta1) treatment induced EMT in A549 and H1299 cells,
      and downregulation of miR-3127-5p could result in the similar effect.
      Mechanically, we demonstrated that frizzled-4 (FZD4) is a target gene and miR
      3127-5p exerts its effects by regulating the Wnt/beta-catenin signaling. In
      addition, the expression levels of FZD4 and miR-3127-5p were also negatively
      associated in both clinical and xenografted tumors. Overall, these findings
      suggest that downregulation of miR-3127-5p promotes EMT through activating the
      Wnt/FZD4/beta-catenin signaling pathway and may represent a therapeutic target
      for NSCLC metastasis.

PMID- 29566282
TI  - Oleanolic acid induces osteosarcoma cell apoptosis by inhibition of Notch
      signaling.
AB  - Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential
      antitumor activity in several tumor cell lines. Although the inhibition effects
      of OA on proliferation and survival in human cancers have been confirmed, the
      potential mechanism underlying OA-induced osteosarcoma cell death has not yet
      been fully elucidated. Our results in this study showed that OA inhibits
      proliferation and viability of osteosarcoma cells in a dose-dependent manner.
      Flow cytometry assays revealed that apoptosis in osteosarcoma cells was
      significantly induced by OA treatment, while this induction was blocked by
      Jagged1-mediated activation of Notch signaling. Western blot analysis and a
      mitochondrial membrane potential assay demonstrated that OA functions through the
      mitochondrial apoptosis pathway. More importantly, our data revealed that OA
      treatment interrupted the balance between pro-apoptotic factors and anti
      apoptotic factors in osteosarcoma cells by inhibition of the Notch signaling
      pathway. These data suggest that OA induces osteosarcoma cell apoptosis by
      targeting mitochondria in a Notch signaling-dependent manner. Thus, OA may be a
      promising drug for adjuvant chemotherapy in osteosarcoma.

PMID- 29566283
TI  - Aberrant methylation-mediated downregulation of long noncoding RNA C5orf66-AS1
      promotes the development of gastric cardia adenocarcinoma.
AB  - As a long non-coding RNA, C5orf66-AS1 is located at 5q31.1. Downregulation and
      aberrant hypermethylation of C5orf66-AS1 have been detected in a limited several
      tumors. However, the biological role and distribution of methylated CpG sites of
      C5orf66-AS1 in gastric cardia adenocarcinoma (GCA) development and prognosis are
      poorly clarified. The present study was to investigate the expression status and
      function of C5orf66-AS1 in GCA, and to detect the distribution of methylated CpG
      sites within the three CpG islands of the promoter and gene body of C5orf66-AS1,
      further to clarify its prognostic value in GCA patients. C5orf66-AS1 was
      significantly downregulated in GCA tissues and cell lines, and the expression
      level was associated with TNM stage, pathological differentiation, lymph node
      metastasis, and distant metastasis or recurrence. The expression level of C5orf66
      AS1 was significantly increased in cancer cells after treated with 5-Aza-dC.
      Further methylation analysis demonstrated that the aberrant hypermethylation of
      the regions around the transcription start site of C5orf66-AS1 was more tumor
      specific and was associated with its expression. Moreover, Sp1 may upregulate
      C5orf66-AS1 expression and CpG sites hypermethylation within the binding sites
      may abrogate Sp1 binding. In addition, C5orf66-AS1 inhibited gastric cancer cell
      proliferation and invasion, and the dysregulation and hypermethylation of the
      regions around the transcription start site of C5orf66-AS1 were associated with
      poorer GCA patients' survival. These findings suggest that aberrant
      hypermethylation-mediated downregulation of C5orf66-AS1 may play important roles
      in GCA tumorigenesis and C5orf66-AS1 may serve as a potential prognostic marker
      in predicting GCA patients' survival.

PMID- 29566284
TI  - Clinical Effect of C2 Peripheral Nerve Field Stimulation Using Electroacupuncture
      for Primary Headache.
AB  - OBJECTIVE: We applied C2 peripheral nerve field stimulation using
      electroacupuncture (EA-C2-PNfS) for primary headache, and investigated its
      clinical effectiveness. MATERIALS AND METHODS: Fifty-four primary headache
      patients (10 men, 44 women) with a mean age of 48.6 +/- 15.0 years underwent EA
      C2-PNfS for three months. We used questionnaires to assess outcomes; pain
      intensity (11-point numerical rating scale [NRS]), quality of daily life
      (Headache Impact Test [HIT-6]), depression (Self-Rating Depression Scale [SDS]).
      Monthly headache days and acute headache medication days were obtained from
      diaries. RESULTS: The headache intensity significantly declined after the EA-C2
      PNfS with reduction of NRS pain scale; 7.4 +/- 1.9 at baseline, 4.9 +/- 2.9 at
      three month (p < 0.001). Both HIT-6 and SDS showed significant improvement (p <
      0.001). Some patients showed moderate depression in SDS before treatment, that
      was alleviated in patients with tension-type headache after the EA-C2-PNfS.
      Monthly headache days significantly decreased from 18.0 +/- 9.0 at one month to
      14.0 +/- 10.2 at three months (p < 0.001), accompanied with reduction of the
      monthly acute headache medication days from 8.0 +/- 6.7 to 6.4 +/- 6.5 (p =
      0.003). CONCLUSIONS: EA-C2-PNfS was successfully used for reducing severity and
      disability in primary headache patients. We conclude that EA-C2-PNfS is a
      favorable option for medically intractable primary headache as less-invasive
      neuromodulation.

PMID- 29566285
TI  - Non-Uniform and Absolute Minimal Sampling for High-Throughput Multidimensional
      NMR Applications.
AB  - Many biomolecular NMR applications can benefit from the faster acquisition of
      multidimensional NMR data with high resolution and their automated analysis and
      interpretation. In recent years, a number of non-uniform sampling (NUS)
      approaches have been introduced for the reconstruction of multidimensional NMR
      spectra, such as compressed sensing, thereby bypassing traditional Fourier
      transform processing. Such approaches are applicable to both biomacromolecules
      and small molecules and their complex mixtures and can be combined with
      homonuclear decoupling (pure shift) and covariance processing. For homonuclear 2D
      TOCSY experiments, absolute minimal sampling (AMS) permits the drastic shortening
      of measurement times necessary for high-throughput applications for
      identification and quantification of components in complex biological mixtures in
      the field of metabolomics. Such TOCSY spectra can be comprehensively represented
      by graphic theoretical maximal cliques for the identification of entire spin
      systems and their subsequent query against NMR databases. Integration of these
      methods in webservers permits the rapid and reliable identification of mixture
      components. Recent progress is reviewed in this Minireview.

PMID- 29566286
TI  - The Breath-Hold Acceleration Index: A New Method to Evaluate Cerebrovascular
      Reactivity using Transcranial Doppler.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular reactivity (CR) is an ideal biomarker to
      detect cerebrovascular damage. CR can be quantified by measuring changes in
      cerebral blood flow velocity (CBFV) resulting from a CO2  vasodilatory stimulus,
      often using the breath-holding index (BHI). In this method, transcranial Doppler
      (TCD) ultrasound is used to measure CBFV changes in the middle cerebral artery
      (MCA) during a breath-hold maneuver. Despite its convenience, BHI has high
      variability. Changing body position may contribute to potential variability. It
      is important to determine if CR differs with body position. The aims of this
      study were, first, to propose an alternative, more robust index to evaluate CR
      using a breath-hold maneuver; second, investigate the effect of body position on
      CR measured with conventional (BHI) and a new proposed index. METHODS: Ten
      healthy young volunteers held their breath for 30 seconds on a tilt table. CR was
      calculated at five different angles using two indices: the conventional BHI, and
      the breath-hold acceleration index (BHAI), a new index obtained by linear
      regression of the most linear portion of the mean velocity change during the
      breath-hold maneuver. The regression represents acceleration (change in blood
      flow velocity per unit of time) sampled at each cardiac cycle. RESULTS: The mean
      coefficient of variation was 43.7% lower in BHAI in comparison with BHI. Neither
      index was statistically significant between body positions (P > .05).
      CONCLUSIONS: BHAI has less variability in comparison with the conventional
      standard BHI. Additionally, neither index showed statistical significance in CR
      based on change in body position.

PMID- 29566287
TI  - Effect of Foetal Bovine Serum on sperm motility, acrosome reaction and spermatic
      interaction to zona pellucida in alpacas (Vicugna pacos).
AB  - The use of foetal bovine serum (FBS) in cell culture media is quite common.
      However, little is known about the effect of FBS on sperm. The severe
      difficulties in alpaca reproduction demand the search of new methods for in vitro
      reproductive management. In the present study, we use for the first time FBS as a
      supplement in the culture medium for sperm in alpaca, and the effect of FBS on
      motility, acrosome reaction and sperm binding to the zona pellucida in this
      species was evaluated. A concentration of 10% v/v FBS was used. The sperm
      motility with FBS at the first hour was 32.8% (vs. control = 30.0%), whereas at
      the second hour sperm motility with FBS was 30.2% (vs. control = 28.8%). The
      acrosome reaction reached an average of 44.0% for treatment with FBS (vs. control
      = 30.1%). The sperm-zona pellucida binding assay showed that the samples
      incubated with FBS had an average of 2.7 bound sperm (vs. control = 1.7). Only a
      significant difference was observed for sperm motility at the first hour and for
      the acrosome reaction. It is concluded that FBS favours the capacitation of sperm
      in alpaca.

PMID- 29566288
TI  - Retrograde Placement of High Cervical Electrodes: A Technical Refinement and Case
      Series.
AB  - INTRODUCTION: Cervical cord stimulation is used in the treatment of chronic
      (neuropathic) pain syndromes refractory to conservative treatments. Several
      authors describe different techniques for the placement of cervical electrodes.
      Electrodes can be placed retrogade [Correction added on 03 April 2018 after first
      online publication: the word "plased" has been changed to "placed".]. In this
      article, we describe a refinement on how to dissect the dorsal meningo-vertebral
      ligaments to decrease the risk of complications. PATIENTS AND METHODS: Twenty
      eight patients received a permanent cervical spinal cord stimulator. A C0-C1
      retrograde insertion was performed with careful dissection of the meningo
      vertebral ligaments. Complications were registered during the follow-up (mean
      44.6 months [SD = 43, range 1-162 months]). RESULTS: Six complications were
      observed 93% of the patients reported a significant reduction in pain.
      CONCLUSIONS: We describe an additional surgical detail for the known procedure
      for retrograde placement of high cervical plate electrodes. This surgical detail
      might result in a lower risk of complications. We present a case series of 28
      patients to support this hypothesis.

PMID- 29566289
TI  - Short Interval Intracortical Inhibition Responses to Low-Frequency Repetitive
      Transcranial Magnetic Stimulation Under Multiple Interstimulus Intervals and
      Conditioning Intensities.
AB  - BACKGROUND: The extent to which short interval intracortical inhibition (SICI)
      responds to low-frequency repetitive transcranial magnetic stimulation (rTMS)
      remains inconclusive with reports of increased, decreased and unchanged response
      following modulation. The aim of this study was to systematically investigate if
      the variability of SICI following rTMS is explained by the interstimulus interval
      (ISI) and/or the conditioning stimulus intensity (CSI). METHODS: Two experiments
      with pretesting/posttesting and an rTMS session (1 Hz, 90% RMT, 900 pulses) were
      done. Experiment I (N = 15): SICI with multiple ISIs (1.0-4.0 msec, 0.2 msec
      increment). Experiment II (N = 15): SICI with CSIs (50-95% of RMT, 5% increment).
      In both experiments, the cortical silent period (cSP) was also collected.
      RESULTS: After low-frequency rTMS, no significant change (p > 0.10) in SICI at
      any specific ISI or CSI was observed, nor did the optimal ISI or CSI change.
      However, a significant decrease was observed in SICI responses when assessed
      under the range of ISIs (p = 0.0001), but not CSIs. cSP inhibition increased
      significantly (p < 0.0015) for both experiments. CONCLUSIONS: The optimal ISI or
      CSI did not shift or reveal SICI changes after inhibitory rTMS. However, when the
      whole curve of SICI responses were evaluated from a wide range of ISIs, a
      decrease in inhibition was found. The contrast between the results of individual
      ISI tests and the wide range of ISI assessment may be due to higher intersubject
      variability of SICI and/or sample size, rendering traditional SICI testing
      methods ineffective for measuring changes in inhibition. Further, it is possible
      that rTMS modulates GABAA and GABAB mediated inhibitory processes differently,
      which would explain the conflicting results for SICI and cSP.

PMID- 29566290
TI  - Morphology of alpaca (Vicugna pacos) embryos in the first third of pregnancy.
AB  - The breeding of South American camelids is the main economic activity of the high
      Andean region of South America and it, is potentially, the most profitable
      resource in of the Puna environmental conditions of the Puna. The duration of the
      gestation in alpaca is 339.7 +/- 12 days. The objective of the present work was
      to macroscopically and microscopically describe the ontogenic development of the
      splanchnic cavities of the alpaca and to determine the gestational time in which
      the post-cranial ossification centers are observed in the embryos/fetuses of this
      species, from day 21 to 107 of gestation. The documentation of normal ontogenic
      development, which is vacant for this period, is of the utmost importance to
      understand the consequences of the alterations at the different gestational
      times, as well as for the estimation of the gestational age in the case of
      abortions. Forty-seven alpaca specimens of both sexes, at different times of
      their gestational development, collected during slaughter at local
      slaughterhouses of the Department of Huancavelica, Peru, were evaluated.
      Specimens were assigned to seven groups according to their morphological
      characteristics. The embryogenesis in the alpaca was characterized by a series of
      changes comparable to those occurring in other mammals with similar gestational
      periods. Despite these similarities, species differences were found in some
      organs as stomach, which are observed too in adult individuals.

PMID- 29566291
TI  - The First Silicon(IV) Corrole Complexes: Synthesis, Structures, Properties, and
      Formation of a MU-Oxo Dimer.
AB  - The first SiIV corrole complexes were synthesized in good yields by treatment of
      meso-triarylcorroles with tetrachlorosilane in 1,2-dichloroethane at 60  degrees
      C. The central silicon atom possesses a square-pyramidal coordination geometry
      with slightly longer Si-N bond lengths as compared with those of known
      triazacorrole SiIV complexes. The SiIV corrole complexes exhibit sharp and blue
      shifted absorption spectra and larger fluorescence quantum yields as compared
      with the corresponding free-base corroles. A MU-oxo dimer of a SiIV corrole was
      synthesized upon treatment with methanesulfonyl chloride in pyridine at 100 
      degrees C. This dimer shows a face-to-face structure with a 90 degrees  twist in
      the solid state. Although the dimer exhibits a blue-shifted Soret band,
      reflecting the face-to-face geometry, it displays a largely red-shifted and broad
      fluorescence spectrum with a large Stokes shift, suggesting a large structural
      change in the S1 state. These intriguing optical properties have been
      comprehensively studied by magnetic circular dichroism (MCD) spectroscopy,
      femtosecond transient absorption (fs-TA) measurements, and theoretical
      calculations.

PMID- 29566292
TI  - Branched Fatty Acyl Esters of Hydroxyl Fatty Acids (FAHFAs), Appealing Beneficial
      Endogenous Fat against Obesity and Type-2 Diabetes.
AB  - After a brief overview of the biological significance of FAHFAs, the present
      Minireview highlights the different strategies developed for their chemical
      syntheses. The term "FAHFAs" has been introduced in 2014 for fatty acyl esters of
      hydroxyl fatty acids, found in adipocytes, with antidiabetic properties. However,
      many other natural products contain this type of branched lipids in their
      structure. This review was then extended to the synthesis of these subunits, even
      though the length of the lipid chains and the location of the ester linkages are
      different, since the developed strategies may be applied to the synthesis of
      "FAHFA".

PMID- 29566293
TI  - Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro
      Phenols: Periodic Relatives Behaving Differently.
AB  - The possible antioxidant reaction mechanisms of recently synthesized and tested
      alkylseleno (telluro) phenols have been explored using density functional theory
      by considering two solvents physiologically relevant, water and pentylethanoate
      (PE). In addition, the possible pathway for the antioxidant regeneration with
      ascorbic acid has been investigated. Results show that selenium and tellurium
      systems follow different chemical behaviors. In particular, the alkylseleno
      phenol (ebselenol) antioxidant activity is justified through a sequential proton
      loss-electron-transfer mechanism in water media, whereas in PE the hydrogen-atom
      transfer process is favored. In the case of the tellurium derivative, the oxygen
      transfer mechanism represents the preferential one. Furthermore, electronic
      properties have been analyzed to rationalize the different reactivity of the
      selenium- and tellurium-containing systems. To confirm the results, smaller but
      similar systems were also investigated. The calculated data support the different
      mechanism (Se vs. Te) proposals.

PMID- 29566294
TI  - Inflammatory cytokine-mediated induction of serine racemase in atopic dermatitis.
AB  - Serine racemase (SR) is an enzyme that catalyses the synthesis of d-serine, an
      endogenous coagonist for N-methyl-D-aspartate (NMDA)-type glutamate receptor in
      the central nervous system. Our previous study demonstrated that SR was expressed
      in the epidermis of wild-type (WT) mice but not in SR knockout (KO) mice. In
      addition, SR immune-reactivity was only found in the granular and cornified
      layers of the epidermis in WT mice. These findings suggested that SR is involved
      in the differentiation of epidermal keratinocytes and the formation of the skin
      barrier. However, its role in skin barrier dysfunction such as atopic dermatitis
      (AD) remains elusive. AD is a chronic inflammatory disease of skin, and the
      clinical presentation of AD has been reported to be occasionally associated with
      psychological factors. Therefore, this study examined the content of d-serine in
      stratum corneum in AD patients and healthy controls using a tape-stripping
      method. Skin samples were collected from the cheek and upper arm skin of AD
      patient's lesion and healthy individuals. The d-serine content was significantly
      increased in the involved skin of AD in comparison with healthy individuals. An
      immunohistochemical analysis also revealed an increased SR expression in the
      epidermis of AD patients. Furthermore, the SR expression in cultured human
      keratinocytes was significantly increased by the stimulation with tumour necrosis
      factor -alpha or macrophage migration inhibitory factor. Taken together, these
      findings suggest that d-serine expressed particularly strongly in AD lesional
      skin and that the SR expression in the keratinocytes is linked to inflammatory
      cytokines.

PMID- 29566295
TI  - Qualitative and quantitative ultrasound attributes of maternal-foetal structures
      in pregnant ewes.
AB  - The aim of this study was to examine foetal organs and placental tissue to
      establish a correlation between the changes in the composition of these
      structures associated with their maturation and the ultrasonographic
      characteristics of the images. Twenty-four pregnant ewes were included in the
      study. Ultrasonography assessments were performed in B-mode, from the ninth
      gestational week until parturition. The lungs, liver and kidneys of foetuses and
      placentomes were located in transverse and longitudinal sections to evaluate the
      echogenicity (hypoechoic, isoechoic, hyperechoic or mixed) and echotexture
      (homogeneous and heterogeneous) of the tissues of interest. For quantitative
      evaluation of the ultrasonographic characteristics, it was performed a
      computerized image analysis using a commercial software (Image ProPlus(r) ). Mean
      numerical pixel values (NPVs), pixel heterogeneity (standard deviation of NPVs)
      and minimum and maximum pixel values were measured by selecting five circular
      regions of interest in each assessed tissue. All evaluated tissues presented
      significant variations in the NPVs, except for the liver. Pulmonary NPVmean,
      NPVmin and NPVmax decreased gradually through gestational weeks. The renal
      parameters gradually decreased with the advancement of the gestational weeks
      until the 17th week and later stabilized. The placentome NPVmean, NPVmin and
      NPVmax decreased gradually over the course of weeks. The hepatic tissue did not
      show echogenicity and echotexture variations and presented medium echogenicity
      and homogeneous echotexture throughout the experimental period. It was concluded
      that pixels numerical evaluation of maternal-foetal tissues was applicable and
      allowed the identification of quantitative ultrasonographic characteristics
      showing changes in echogenicity related to gestational age.

PMID- 29566296
TI  - Multistate Photoswitches: Macrocyclic Dihydroazulene/Azobenzene Conjugates.
AB  - Molecules comprised of three covalently linked bi-stable switches can exist in
      states described by a combination of binary numbers, one for each individual
      switch: ?000?, ?001?, etc. Here we have linked three photo-/thermoswitches
      together in a rigid macrocyclic structure, one azobenzene (bit no 1) and two
      dihydroazulenes (DHAs; bits no 2 and 3) and demonstrate how electronic
      interactions and unfavorable strain in some states can be used to control the
      speed by which a certain state is reached. More specifically, upon irradiation of
      state ?000?, the AZB isomerizes from trans to cis and the two DHAs to
      vinylheptafulvenes (VHFs), generating ?111?. The thermal VHF-to-DHA back
      reactions from this state also occur stepwise and can be accelerated by photo
      induced AZB cis-to-trans conversion, proceeding via ?011? to ultimately furnish
      ?000?. Overall, the accessibility to a specific state of one bit was found to
      depend on the states of its neighboring bits.

PMID- 29566297
TI  - Visible-Light-Induced Nickel-Catalyzed Negishi Cross-Couplings by Exogenous
      Photosensitizer-Free Photocatalysis.
AB  - The merging of photoredox and transition-metal catalysis has become one of the
      most attractive approaches for carbon-carbon bond formation. Such reactions
      require the use of two organo-transition-metal species, one of which acts as a
      photosensitizer and the other one as a cross-coupling catalyst. We report herein
      an exogenous-photosensitizer-free photocatalytic process for the formation of
      carbon-carbon bonds by direct acceleration of the well-known nickel-catalyzed
      Negishi cross-coupling that is based on the use of two naturally abundant metals.
      This finding will open new avenues in cross-coupling chemistry that involve the
      direct visible-light absorption of organometallic catalytic complexes.

PMID- 29566298
TI  - Impact of thermo-tactile stimulation on the speed and efficiency of swallowing: a
      systematic review.
AB  - BACKGROUND: A delayed or absent swallow reflex is common in dysphagia and can
      have a significant impact on swallow safety. Recent clinical practice survey data
      have supported the fact that clinicians continue to use thermo-tactile
      stimulation (TTS) as a strategy to stimulate key nerve pathways and evoke a
      swallow reflex for patients with a delayed or absent swallow reflex. AIMS: To
      conduct a systematic review of the effectiveness of TTS as a compensatory and/or
      rehabilitative tool. METHODS & PROCEDURES: A search performed on CINAHL, Medline
      and Speech Bite identified 599 articles. After removing duplicates, the titles
      and abstracts of 458 articles were assessed for eligibility; 426 articles were
      deemed to be clearly ineligible and the remaining 32 full-text articles were
      further screened for inclusion. Ten of these studies were included in this
      review. MAIN CONTRIBUTION: The results of this review highlight the lack of
      available evidence in this area and give support to the view that there is only
      low-level evidence for use of TTS as a compensatory strategy immediately before a
      swallow. CONCLUSIONS & IMPLICATIONS: There is low-level evidence to support the
      use of TTS. Current best practice would be to use TTS on a case-by-case basis,
      following detailed instrumental assessment and evaluation of its efficacy for an
      individual.

PMID- 29566299
TI  - Dynamic Nuclear Polarization-Enhanced Biomolecular NMR Spectroscopy at High
      Magnetic Field with Fast Magic-Angle Spinning.
AB  - Dynamic nuclear polarization (DNP) is a powerful way to overcome the sensitivity
      limitation of magic-angle-spinning (MAS) NMR experiments. However, the resolution
      of the DNP NMR spectra of proteins is compromised by severe line broadening
      associated with the necessity to perform experiments at cryogenic temperatures
      and in the presence of paramagnetic radicals. High-quality DNP-enhanced NMR
      spectra of the Acinetobacter phage 205 (AP205) nucleocapsid can be obtained by
      combining high magnetic field (800 MHz) and fast MAS (40 kHz). These conditions
      yield enhanced resolution and long coherence lifetimes allowing the acquisition
      of resolved 2D correlation spectra and of previously unfeasible scalar-based
      experiments. This enables the assignment of aromatic resonances of the AP205 coat
      protein and its packaged RNA, as well as the detection of long-range contacts,
      which are not observed at room temperature, opening new possibilities for
      structure determination.

PMID- 29566300
TI  - Are the effects of drugs to prevent and to treat heart failure always concordant?
      The statin paradox and its implications for understanding the actions of
      antidiabetic medications.
AB  - Most treatments for chronic heart failure are effective both in preventing its
      onset and reducing its progression. However, statins prevent the development of
      heart failure, but they do not decrease morbidity and mortality in those with
      established heart failure. This apparent discordance cannot be explained by an
      effect to prevent interval myocardial infarctions. Instead, it seems that the
      disease that statins were preventing in trials of patients with a metabolic
      disorder was different from the disease that they were treating in trials of
      chronic heart failure. The most common phenotype of heart failure in patients
      with obesity and diabetes is heart failure with a preserved ejection fraction
      (HFpEF). In this disorder, the anti-inflammatory effects of statins might
      ameliorate myocardial fibrosis and cardiac filling abnormalities, but these
      actions may have little relevance to patients with heart failure and a reduced
      ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and
      stretch. These distinctions may explain why statins were ineffective in trials
      that focused on HFrEF, but have been reported to produce favourable effects in
      observational studies of HFpEF. Similarly, selective cytokine antagonists were
      ineffective in HFrEF, but have been associated with benefits in HFpEF. These
      observations may have important implications for our understanding of the effects
      of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have
      had neutral effects on heart failure events in people at risk for HFpEF, but have
      exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2
      inhibitors, which exert anti-inflammatory effects and reduce heart failure events
      in patients who are prone to HFpEF, may not be effective in HFrEF. The
      distinctions between HFrEF and HFpEF may explain why the effects of drugs on
      heart failure events in diabetes trials may not be relevant to their use in
      patients with systolic dysfunction.

PMID- 29566301
TI  - Graphene: A Cathode Material of Choice for Aluminum-Ion Batteries.
AB  - The pairing of an aluminum anode with a cathode of high energy and power density
      determines the future of aluminum-ion battery technology. The question is-"Is
      there any suitable cathode material which is capable of storing sufficiently
      large amount of trivalent aluminum-ions at relatively higher operating
      potential?". Graphene emerges to be a fitting answer. Graphene emerged in the
      research arena of aluminum-ion battery merely three years ago. However, research
      progress in this front has since been tremendous. Outperforming all other known
      cathode materials, several remarkable breakthroughs have been made with graphene,
      in offering extraordinary energy density, power density, cycle life, thermal
      stability, safety and flexibility. The future of the Al-graphene couple is indeed
      bright. This Minireview highlights the electrochemical performances, advantages
      and challenges of using graphene as the cathode in aluminum-ion batteries in
      conjugation with chloroaluminate based electrolytes. Additionally, the complex
      mechanism of charge storage in graphene is also elaborated.

PMID- 29566302
TI  - Sight-threatening complications of cosmetic iris implants.

PMID- 29566303
TI  - Biosecurity practices in Belgian cattle farming: Level of implementation,
      constraints and weaknesses.
AB  - Over the last few years, a shift from curative towards preventive medicine
      occurred in the livestock sector. This led to an increased importance of
      biosecurity to better control infectious diseases by preventing their
      introduction and/or reducing their spread. Farmers are the main responsible
      actors of biosecurity measures (BSM). Existing studies report a low
      implementation level of BSM by the cattle farmers. Barriers such as cost,
      usefulness, importance, workload and lack of knowledge were investigated but the
      decision-making process of farmers related to a given BSM is not yet clarified.
      The objectives of this study were to (i) assess the level of implementation of
      BSM in cattle farms, (ii) assess the correlation between the importance that
      farmers give to a BSM and its effective implementation and (iii) identify the
      main reasons of non-implementation. A randomized survey was implemented in
      Belgium from December 2016 up to April 2017 with face-to-face interviews
      conducted in 100 Belgian farms. A descriptive analysis of data was performed
      using Microsoft Excel(r) and Stata14(r) . Chi-square and Spearman's rank
      correlation tests, respectively, allowed comparing implementation levels in dairy
      herds vs. beef herds and investigating the correlation between the importance
      that farmers give to a BSM and its implementation level. Biosecurity measures
      were poorly implemented to prevent disease introduction through direct contact
      and almost not to avoid indirect transmission. Some measures showed a significant
      difference in terms of implementation level between beef and dairy herds. A
      positive correlation was highlighted between the importance that farmers give to
      a BSM and its actual effective implementation. Perceived lack of efficiency,
      feasibility and usefulness are the reasons most often mentioned for non
      implementation. Other factors potentially influencing the decision-making process
      should be further investigated and clarified. Evidence-based studies would be
      useful to convince the farmers of the need of implementing BSM.

PMID- 29566304
TI  - Oligodendrocyte gene expression is reduced by and influences effects of chronic
      social stress in mice.
AB  - Oligodendrocyte gene expression is downregulated in stress-related
      neuropsychiatric disorders, including depression. In mice, chronic social stress
      (CSS) leads to depression-relevant changes in brain and emotional behavior, and
      the present study shows the involvement of oligodendrocytes in this model. In
      C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with prefrontal
      cortex, amygdala and hippocampus from CSS and controls; a gene enrichment
      database for neurons, astrocytes and oligodendrocytes was used to identify cell
      origin of deregulated genes, and cell deconvolution was applied. To assess the
      potential causal contribution of reduced oligodendrocyte gene expression to CSS
      effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide
      phosphodiesterase (Cnp1) on a BL/6 background were studied; a 2 genotype
      (wildtype, Cnp1+/- ) * 2 environment (control, CSS) design was used to
      investigate effects on emotional behavior and amygdala microglia. In BL/6 mice,
      in prefrontal cortex and amygdala tissue comprising gray and white matter, CSS
      downregulated expression of multiple oligodendroycte genes encoding myelin and
      myelin-axon-integrity proteins, and cell deconvolution identified a lower
      proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte
      proteins in amygdala gray matter did not yield evidence for reduced translation,
      suggesting that CSS impacts primarily on white matter oligodendrocytes or the
      myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in
      Cnp1+/- mice specifically; using ionized calcium-binding adaptor molecule 1
      (IBA1) expression, microglia activity was increased additively by Cnp1+/- and CSS
      in amygdala gray and white matter. This study provides back-translational
      evidence that oligodendrocyte changes are relevant to the pathophysiology and
      potentially the treatment of stress-related neuropsychiatric disorders.

PMID- 29566305
TI  - Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell
      proliferation and migration in diabetic atherosclerosis.
AB  - Ginsenoside 20(R/S)-Rg3, as a natural peroxisome proliferator-activated receptor
      gamma (PPARgamma) ligand, has been reported to exhibit differential biological
      effects. It is of great interest to understand the stereochemical selectivity of
      20(R/S)-Rg3 and explore whether differential PPARgamma activation by Rg3
      stereoisomers, if it exists, could lead to differential physiological outcome and
      therapeutic effects in diabetic atherosclerosis. Here, we investigated the
      binding modes of 20(R/S)-Rg3 stereoisomers in the PPARgamma ligand-binding domain
      (PPARgamma-LBD) using molecular modelling and their effects on smooth muscle cell
      proliferation and migration induced by advanced glycation end products (AGEs).
      The results revealed that 20(S)-Rg3 exhibited stronger antiproliferative and
      antimigratory effects due to stronger PPARgamma activation. To validate the in
      vitro results, we used a mice model with diabetic atherosclerosis and obtained
      that 20(S)-Rg3 markedly reduced the plaque size secondary to reducing the
      proliferation and migration of VSMCs, while the plaques were more stable due to
      improvements in other plaque compositions. The results shed light on the
      structural difference between Rg3 stereoisomers that can lead to significant
      differential physiological outcome, and the (S)-isomer seems to be the more
      potent isomer to be developed as a promising drug for diabetic atherosclerosis.

PMID- 29566306
TI  - Bovine anaplasmosis and tick-borne pathogens in cattle of the Galapagos Islands.
AB  - A cross-sectional study was conducted to determine the species of Anaplasma spp.
      and estimate its prevalence in cattle of the three main cattle-producing
      Galapagos Islands (Santa Cruz, San Cristobal and Isabela) using indirect PCR
      assays, genetic sequencing and ELISA. Ticks were also collected from cattle and
      scanned for 47 tick-borne pathogens in a 48 * 48 real-time PCR chip. A mixed
      effects logistic regression was performed to identify potential risk factors
      explaining Anaplasma infection in cattle. A. phagocytophilum was not detected in
      any of the tested animals. Genetic sequencing allowed detection of A. platys-like
      strains in 11 (36.7%) of the 30 Anaplasma spp.-positive samples analysed. A.
      marginale was widespread in the three islands with a global between-herd
      prevalence of 100% [89; 100]95% CI and a median within-herd prevalence of 93%. A
      significant association was found between A. marginale infection and age with
      higher odds of being positive for adults (OR = 3.3 [1.2; 9.9]95% Bootstrap CI ).
      All collected ticks were identified as Rhipicephalus microplus. A. marginale,
      Babesia bigemina, Borrelia theileri and Francisella-like endosymbiont were
      detected in tick pools. These results show that the Galapagos Islands are endemic
      for A. marginale.

PMID- 29566307
TI  - Enhancing amplification of late-outgrowth endothelial cells by bilobalide.
AB  - Transfusion of autologous late-outgrowth endothelial cells (OECs) is a promising
      treatment for restenosis after revascularization. Preparing cells by in vitro
      amplification is a key step to implement the therapy. This study aimed to
      demonstrate that bilobalide, a terpenoid, enhances the OEC amplification. Human-,
      rabbit- and rat OECs and a mouse femoral artery injury model were used. Expanding
      OECs used endothelial growth medium-2 as the standard culture medium while
      exploring the mechanisms used endothelial basal medium-2. Proliferation assay
      used MTT method and BrdU method. Migration assay used the modified Boyden
      chamber. Intracellular nitric oxide, superoxide anion, hydroxyl
      radical/peroxynitrite and H2 O2 were quantified with DAF-FM DA, dihydroethidium,
      hydroxyphenyl fluorescein and a H2 O2 assay kit, respectively. Activated ERK1/2
      and eNOS were tested with the Western blot. Bilobalide concentration-dependently
      enhanced OEC number increase in vitro. Transfusion of bilobalide-based human OECs
      into femoral injured athymia nude mouse reduced the intimal hyperplasia.
      Bilobalide promoted OEC proliferation and migration and increased the
      intracellular nitric oxide level. L-NAME, a NOS inhibitor, inhibits but not
      abolishes OEC proliferation, migration and ERK1/2 activation. Bilobalide
      concentration-dependently enhanced the eNOS Ser-1177 phosphorylation and Thr-495
      dephosphorylation in activated OECs. Bilobalide alleviates the increase in
      hydroxyl radical/peroxynitrite, superoxide anion and H2 O2 in proliferating OECs.
      In conclusion, nitric oxide plays a partial role in OEC proliferation and
      migration; bilobalide increases OEC nitric oxide production and decreases nitric
      oxide depletion, promoting the OEC number increase; Bilobalide-based OECs are
      active in vivo. The findings may simplify the preparation of OECs, facilitating
      the implementation of the autologous-OECs-transfusion therapy.

PMID- 29566308
TI  - Functional mesoporous silica nanoparticles for bio-imaging applications.
AB  - Biomedical investigations using mesoporous silica nanoparticles (MSNs) have
      received significant attention because of their unique properties including
      controllable mesoporous structure, high specific surface area, large pore volume,
      and tunable particle size. These unique features make MSNs suitable for
      simultaneous diagnosis and therapy with unique advantages to encapsulate and load
      a variety of therapeutic agents, deliver these agents to the desired location,
      and release the drugs in a controlled manner. Among various clinical areas,
      nanomaterials-based bio-imaging techniques have advanced rapidly with the
      development of diverse functional nanoparticles. Due to the unique features of
      MSNs, an imaging agent supported by MSNs can be a promising system for developing
      targeted bio-imaging contrast agents with high structural stability and enhanced
      functionality that enable imaging of various modalities. Here, we review the
      recent achievements on the development of functional MSNs for bio-imaging
      applications, including optical imaging, magnetic resonance imaging (MRI),
      positron emission tomography (PET), computed tomography (CT), ultrasound imaging,
      and multimodal imaging for early diagnosis. With further improvement in
      noninvasive bio-imaging techniques, the MSN-supported imaging agent systems are
      expected to contribute to clinical applications in the future. This article is
      categorized under: Diagnostic Tools > In vivo Nanodiagnostics and Imaging
      Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

PMID- 29566309
TI  - Alpha B-crystallin promotes the invasion and metastasis of gastric cancer via NF
      kappaB-induced epithelial-mesenchymal transition.
AB  - Alpha B-crystallin (CRYAB) is overexpressed in a variety of cancers. However,
      little is known about its specific function and regulatory mechanism in gastric
      cancer. Here, we first explore the role of CRYAB in gastric cancer progression
      and metastasis. The expression of CRYAB was determined by western blot and
      immunohistochemistry in gastric cancer tissues. Besides, methods including stably
      transfected against CRYAB into gastric cancer cells, western blot, migration and
      invasion assays in vitro and metastasis assay in vivo were also conducted. The
      expression of CRYAB is up-regulated in gastric cancer tissues compared with
      matched normal tissues. High expression level of CRYAB is closely correlated with
      cancer metastasis and shorter survival time in patients with gastric cancer.
      Additionally, CRYAB silencing significantly suppresses epithelial-mesenchymal
      transition (EMT), migration and invasion of gastric cancer cells in vitro and in
      vivo, whereas CRYAB overexpression dramatically reverses these events.
      Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via
      nuclear factor-kappa-gene binding (NF-kappaB)-regulated EMT. These findings
      suggest that CRYAB expression predicts a poor prognosis in patients with gastric
      cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion
      via EMT, mediated by the NF-kappaB signalling pathway, thus possibly providing a
      novel therapeutic target for gastric cancer.

PMID- 29566310
TI  - DC-CIK cells derived from ovarian cancer patient menstrual blood activate the
      TNFR1-ASK1-AIP1 pathway to kill autologous ovarian cancer stem cells.
AB  - Ovarian cancer stem cells (OCSCs) are highly carcinogenic and have very strong
      resistance to traditional chemotherapeutic drugs; therefore, they are an
      important factor in ovarian cancer metastasis and recurrence. It has been
      reported that dendritic cell (DC)-cytokine-induced killer (CIK) cells have
      significant killing effects on all cancer cells across many systems including the
      blood, digestive, respiratory, urinary and reproductive systems. However, whether
      DC-CIK cells can selectively kill OCSCs is currently unclear. In this study, we
      collected ovarian cancer patient menstrual blood (OCPMB) samples to acquire
      mononuclear cells and isolated DC-CIK cells in vitro. In addition, autologous
      CD44+/CD133+ OCSCs were isolated and used as target cells. The experimental
      results showed that when DC-CIK cells and OCSCs were mixed and cultured in vitro
      at ratios of 5:1, 10:1 and 50:1, the DC-CIK cells killed significant amounts of
      OCSCs, inhibited their invasion in vitro and promoted their apoptosis. The qPCR
      and Western blot results showed that DC-CIK cells stimulated high expression
      levels and phosphorylation of TNFR1, ASK1, AIP1 and JNK in OCSCs through the
      release of TNF-alpha. After the endogenous TNFR1 gene was knocked out in OCSCs
      using the CRISPR/Cas9 technology, the killing function of DC-CIK cells on target
      OCSCs was significantly attenuated. The results of the analyses of clinical
      samples suggested that the TNFR1 expression level was negatively correlated with
      ovarian cancer stage and prognosis. Therefore, we innovatively confirmed that DC
      CIK cells derived from OCPMB could secret TNF-alpha to activate the expression of
      the TNFR1-ASK1-AIP1-JNK pathway in OCSCs and kill autologous OCSCs.

PMID- 29566311
TI  - IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma
      japonicum-infected mice.
AB  - In schistosomiasis japonica and mansoni, parasite eggs trapped in host liver
      elicit severe liver granulomatous inflammation that subsequently leads to
      periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages
      are critical for granuloma formation and the development of liver fibrosis during
      schistosomiasis. However, whether the aberrant regulation of macrophage autophagy
      has an effect on the development of liver immunopathology in schistosomiasis
      remains to be elucidated. In this study, we showed that Schistosoma japonicum (S.
      japonicum) egg antigen (SEA)-triggered macrophage autophagy limited the
      development of pathology in host liver. However, engagement of IL-7 receptor (IL
      7R/CD127) on macrophages by S. japonicum infection-induced IL-7 significantly
      suppressed SEA-triggered macrophage autophagy, which led to an enhanced liver
      pathology. In addition, anti-IL-7 neutralizing antibody or anti-CD127 blocking
      antibody treatment increased macrophage autophagy and suppressed liver pathology.
      Finally, we demonstrated that IL-7 protects macrophage against SEA-induced
      autophagy through activation of AMP-activated protein kinase (AMPK). Our study
      reveals a novel role for IL-7 in macrophage autophagy and identifies AMPK as a
      novel downstream mediator of IL-7-IL-7R signalling and suggests that manipulation
      of macrophage autophagy by targeting IL-7-IL-7R signalling may have the potential
      to lead to improved treatment options for liver pathogenesis in schistosomiasis.

PMID- 29566312
TI  - Outcome assessment for Brachial Plexus birth injury. Results from the iPluto
      world-wide consensus survey.
AB  - There is no consensus regarding strategies to optimally treat children with a
      brachial plexus birth injury (BPBI). Comparison of outcome data presented by
      different centers is impossible due to the use of (1) many different outcome
      measures to evaluate results; (2) different follow-up periods after
      interventions; and (3) different patient ages at the time of assessment. The goal
      of iPluto (international PLexus oUtcome sTudy grOup) was to define a standardized
      dataset which should be minimally collected to evaluate upper limb function in
      children with BPBI. This dataset must enable comparison of the treatment results
      of different centers if prospectively used. Three rounds of internet surveys were
      used to reach consensus on the dataset. A Delphi-derived technique was applied
      using a nine point Likert scale. Consensus was defined as having attained a
      rating of 7/8/9 by > = 75% of the participants. A total of 59 participants from
      five continents participated in the Second and Third Rounds of the survey.
      Consensus was reached regarding four elements: (1) evaluation should take place
      at the age of 1/3/5/7 years; range of motion in degrees should be measured for
      (2) passive joint movement; (3) active range of motion; and (4) the Mallet score
      should be determined. Consensus on how to asses and report outcome for BPBI was
      only reached on motor items from the "Body Function and Structure" domain.
      Consensus regarding additional ICF domains to obtain a more elaborate set of
      outcome items, should be addressed in future research. (c) 2018 The Authors.
      Journal of Orthopaedic Research(r) Published by Wiley Periodicals, Inc. on behalf
      of the Orthopaedic Research Society. J Orthop Res 36:2533-2541, 2018.

PMID- 29566313
TI  - Spinal Cord Stimulation for the Treatment of Failed Neck Surgery Syndrome:
      Outcome of a Prospective Case Series.
AB  - OBJECTIVES: Spinal cord stimulation (SCS) is an accepted, cost-effective
      treatment option for a variety of chronic pain syndromes, including failed back
      surgery syndrome (FBSS). The application of SCS in the cervical spine,
      particularly for pain after cervical spine surgery, has been drawn into question
      in recent years by payers due to a purported lack of clinical evidence. To
      challenge this claim, we analyzed data from a prospective registry to support the
      use of SCS in the cervical spine for pain after spine surgery. MATERIALS AND
      METHODS: Data from the EMPOWER and PAIN registries were analyzed on patients
      diagnosed with pain after neck surgery (C-FBSS) for the following outcomes:
      patient reported percent pain relief (PRPR), pain disability index (PDI), quality
      of life (QoL), and satisfaction at 3-, 6-, and 12-month post-implantation.
      Statistical analysis was provided for all measures. RESULTS: Fifteen patients
      with C-FBSS were successfully implanted with SCS leads in the cervical spine.
      PRPR was 65.2%, 62.4%, and 71.9% at 3-, 6-, and 12-month post-implantation,
      respectively. PDI scores were significantly reduced from baseline (51.21-23.70 at
      12 months, p = 0.001). At one-year post-implantation, the average overall QoL was
      reported to be improved/greatly improved and patient satisfaction was rated
      satisfied/greatly satisfied. CONCLUSIONS: For many, the application of SCS in the
      neck for pain after surgery is based on the obvious similarities to FBSS or
      anecdotal experience rather than published data. The data contained herein
      suggest SCS for C-FBSS is an effective therapy that improves QoL and patient
      satisfaction, as well as decreasing pain and PDI. The use of successful
      application of neurostimulation as a therapy has largely been predicated on the
      principles of patient selection, implantation technique, and stimulation
      parameters. As such, SCS would appear to be an appropriate and valid treatment
      for C-FBSS that requires further study and investigation to make additional
      recommendations.

PMID- 29566314
TI  - Reproductive Health after the US Elections: Implications for sub-Saharan Africa.

PMID- 29566315
TI  - Knowledge of Abortion Legislation Towards Induced Abortion Among Female
      Preparatory School Students in Dabat District, Ethiopia.
AB  - More than 32% of maternal mortality reported in Ethiopia is due to unsafe
      abortions. Women's knowledge of abortion legislation is a key determinant of the
      utilization of safe abortion services. The objective of this study was to
      determine knowledge of abortion legislation and associated factors among female
      students of Dabat Preparatory School. A quantitative school-based cross-sectional
      study was conducted from May 25-June 7/2014. Data were collected from 234
      randomly selected female students using structured and pre-tested questionnaire.
      Majority of the participants, 147 (62.8%) know that the law in Ethiopia allows
      safe and legal abortion under certain circumstances. Ninety-seven (41.5%) of them
      have poor knowledge towards the legality of induced abortion in Ethiopia. Higher
      family income (OR=2.63, 95% CI=1.22-5.63), knowing the place where safely induced
      abortion can be performed (2.51, 95%CI=1.31-4.81) and current use of
      contraceptive (OR=2.3, 95% CI, 1.1-4.81) are significantly associated with
      knowledge of the abortion legislation. Student's knowledge of the legal status of
      abortion is still low. School-based health education about abortion legislation
      and where it can be safely performed is essential.

PMID- 29566316
TI  - Contraceptive Use among Women in Accra, Ghana: 2003 and 2008.
AB  - Despite a relatively low fertility rate, maternal mortality in Ghana still
      remains high. According to the Ghana Demographic and Health Surveys, about 22% of
      Ghanaian women of reproductive age currently use contraception. We analyzed
      contraceptive use among a representative sample of women in Accra, Ghana, to
      better understand contraceptive use patterns. We used data from two cross
      sectional surveys of a representative cohort of women in Accra. In 2003, 28.9% of
      sexually active women used a contraceptive method. In 2008, 31.5% of sexually
      active women used a contraceptive method. Additionally, we observed high rates of
      discontinuation-from 64.1% among those using longer-acting methods to 82.1% among
      those using traditional methods-between years. Further research on women's
      contraceptive decision-making is needed to explain these patterns and to ensure
      that family planning interventions meet the needs of women in Ghana.

PMID- 29566317
TI  - Sexual Coercion and Violence among Young Women in Nigeria: A Northern and
      Southern Comparison.
AB  - Growing evidence shows that the experience of sexual coercion is fairly prevalent
      among young people and is associated with risky sexual behavior thereafter. This
      study compared patterns and correlates of sexual coercion among young people in
      northern and southern Nigeria. This cross-sectional comparative study
      investigated sexual coercion among 12,626 young women aged between 15 and 24
      years. Respondents were all selected from all six geopolitical zones in Nigeria
      and divided into three northern and southern zones respectively. Relevant
      information was extracted from a nationally representative sample of young women
      from the NDHS survey data and analyzed using SPSS for windows Version 16. About
      54% of respondents in spousal relationship in the northern part of Nigeria
      reported occasionally being physically forced to sex when not wanted compared to
      about 46% southern Nigeria. About, 74% of respondents in the south had been
      sexually coerced or forced by persons other than partner compared to 26% in the
      north. Majority of perpetuators were strangers (22.2%), and friends or
      acquaintances (20.3%). This study indicates that spousal sexual coercion was more
      common in northern Nigeria while sexual coercion occurring in non-spousal
      relationships was more prevalent in southern Nigeria.

PMID- 29566318
TI  - Maternal Near Miss and Quality of Obstetric Care in a Tunisian Tertiary Level
      Maternity.
AB  - This study aimed to determine the frequency and the nature of maternal near miss
      (NM) events in a population of women attending a tertiary level maternity
      hospital in Tunisia and to evaluate the care level of this institution according
      to indicators proposed by the World Health Organization (WHO). We opted for a
      retrospective medical chart review of cases of NM and maternal mortality that
      occurred in the year 2010 at the Farhat Hached Maternity University Hospital. NM
      cases were defined based on the WHO criteria 2009. There were 9957 deliveries, 58
      NM events and one case of maternal death. Haemorrhagic (74.1%) and hypertensive
      disorders (20.7%) were the leading causes of NM. The study showed a low Maternal
      NM Ratio of 5.86/1000 live births, a relatively low mortality index of 1.7 % and
      Severe Maternal Outcome Ratio of 5.96/1000 live births. This was the first study
      to document NM in a Tunisian public maternity. The WHO approach allowed a
      systematic monitoring of quality of maternal health care. There is a low
      frequency of maternal morbidity and mortality at the level of this facility. But,
      more efforts are still needed to document NM events in other types of care
      facilities in Tunisia.

PMID- 29566320
TI  - Prospective Observational Study of the ShangRing Device for Adult Medical Male
      Circumcision in a Routine Clinical Setting in Malawi.
AB  - We evaluated the safety and acceptability of the ShangRing device for male
      circumcision during routine clinical service delivery in Namitete, Malawi. We
      conducted a prospective observational study enrolling 500 HIV-negative men ages
      18 to 49 years at St. Gabriel's Hospital. Participants returned for two follow-up
      visits: the removal visit (day 7 after placement) and the healing check visit
      (day 42 after placement). We assessed pain, adverse events (AEs), acceptability,
      and healing. 500 men were screened; 498 were circumcised using the ShangRing and
      comprised the analysis population. Seven participants (1.4%) experienced moderate
      AEs related to circumcision. 93% were judged to be completely healed at or before
      the day 42 visit; 6% were judged to be healed later than the day 42 visit; 5
      participants (1.0%) were lost to follow-up. 98% of men stated they were very
      satisfied with the appearance of their circumcised penis, and 99.6% would
      recommend ShangRing circumcision to family/friends. Adult male circumcision using
      the ShangRing was safe with a low AE rate at this service delivery site.
      Acceptability factors were also favorable. Addition of the ShangRing device could
      be beneficial to achieving the goals of the circumcision program in Malawi.

PMID- 29566321
TI  - Gender-Based Violence following Social Media Acquaintance in Nigeria.
AB  - In Nigeria, the growth in mobile phone use has provided the opportunity for
      increased access to the internet, and through this, the social media. The social
      media in turn offers tremendous communication benefits but also results in some
      undesirable consequences. One of such is the experience of Gender-Based Violence
      (GBV). Internet searches using Google Search and Google Scholar in addition to
      information available to the authors from news media is reported in this study.
      Five cases were selected for reporting. All cases selected had first contact with
      their perpetrator(s) on Facebook. The perpetrators were usually men, older than
      the victims (24-34 years for perpetrators compared with 17-25 years for the
      victims). The victims experienced physical, psychological, sexual and economic
      violence from their aggressors. One case resulted in the death of the victim,
      while two required hospitalization following severe trauma. Three of the victims
      were raped, while rape was attempted for the other two cases. GBV associated with
      acquaintances made on social media channels is emerging as a new social problem
      in Nigeria. Interventions to educate female social media users about this
      potential danger are urgently necessary.

PMID- 29566319
TI  - A Qualitative Study of Substance use during Pregnancy: Implications for
      Reproductive Healthcare in Western Kenya.
AB  - Women who use alcohol and drugs are often in their childbearing years, creating a
      need for integrated substance abuse and reproductive health services. However,
      our understanding of the social context and drivers of substance use during
      pregnancy, particularly in developing countries, is limited and largely
      unaddressed in clinical care. Our qualitative research explored the reproductive
      health of women of childbearing age who inject drugs and its implications for
      healthcare in Kisumu, Kenya. We used in-depth, semi-structured qualitative
      interviews with 17 women who inject drugs to explore reproductive health topics
      including knowledge, practices, and clinical interactions related to substance
      use during pregnancy. All but one woman had a prior pregnancy and two were
      pregnant during our study. Alcohol and drug use was prevalent throughout
      pregnancy, often described as a coping mechanism for stress. Women received mixed
      advice from family and social contacts regarding alcohol use during pregnancy,
      leading to differing perceptions of its health effects. Healthcare providers
      infrequently screened women for alcohol or drug use. Our analysis highlights the
      need for culturally appropriate alcohol and drug screening and counseling to be
      included in integrated reproductive health services in western Kenya.

PMID- 29566322
TI  - Evaluation of Direct Visual Inspection of the Cervix in Detecting Cytology
      Diagnosed Squamous Intraepithelial Lesion in Women of known HIV Status. A
      Randomized Trial (CANHIV Study).
AB  - A two-arm, open label, randomized study, evaluated the test characteristics of
      visual inspection of cervix with Acetic acid(VIA) and Lugol"s Iodine(VILI) in
      detecting cytology diagnosed squamous intraepithelial lesion(SIL) in 1160 women
      of known HIV status in southwestern Nigerian. Using SIL as reference standard and
      the HIV status masked, VIA and VILI had similar test characteristics except for
      the positive predictive value in which VIA value of 91.5% was significantly
      higher than 77.7% for VILI ( p=0.01). Among HIV positive women, VILI performed
      poorly across all the 4 test characteristics compared to VIA. Among severely
      immuno-compromised HIV positive participants VILI performance was consistently
      below 80% across all test characteristics (sensitivity-70.0%; specificity-66.9%;
      positive predictive value-46.7%; negative predictive value(NPV)-50.0%) compared
      to VIA (Senstivity-71.3%; specificity-88.2%; positive predictive value-83.3%;
      negative predictive value -88.2). Our study shows that VILI is insufficiently
      sensitive and specific in the presence of HIV infection especially in those with
      severe immunosuppression. Based on VIA"s acceptable sensitivity and NPV in all
      situations, it is recommended for cervical cancer screening in HIV positive women
      and in settings of high HIV burden.

PMID- 29566323
TI  - Exploring the Barriers to Breast and Cervical Cancer Screening in Nigeria: A
      Narrative Review.
AB  - Breast and cervical cancers are the most common causes of female cancer-related
      mortality in Nigeria. Early detection and treatment significantly decreases
      cancer mortality rates. Various factors influence uptake of cancer screening.
      Cancer awareness, availability of screening, and treatment facilities alone have
      not been completely successful in improving cancer health behaviour. This review
      aims to identify and summarise the barriers to breast and cervical cancer
      screening uptake in Nigeria. Various databases such as PubMed, Psych Info, Google
      Scholar and EMBASE were extensively searched for existing literature on factors
      influencing breast and cervical cancer screening in Nigeria. Studies retrieved
      explored the major socioeconomic factors affecting women's knowledge, perception,
      and attitude. Embarrassment, low perception of cancer risk, and physician gender
      preference are some of the most common factors that discouraged women from cancer
      screening. Lack of spouse permission and support; belief that cancer is a death
      wish, and societal discrimination are the common sociocultural barriers to
      screening. These factors vary across different regions in Nigeria. Therefore,
      policy makers should make deliberate effort to develop cancer management
      strategies that are tailored to the sociocultural and religious needs in a target
      population. This approach is anticipated to improve uptake and ensure
      sustainability of cancer management.

PMID- 29566324
TI  - Prevalence and Patterns of Sexual Activity during Pregnancy in Kano, Northern
      Nigeria.
AB  - Very little has been documented on sexual activity during pregnancy in northern
      Nigeria. We examined prevalence and factors associated with vaginal intercourse
      during pregnancy in Kano, Nigeria. A cross section of 336 pregnant women
      attending antenatal care at Aminu Kano Teaching Hospital was interviewed using
      pre-tested structured questionnaire. Nearly all respondents (96.4%; n=324)
      reported vaginal intercourse during the index pregnancy. By trimester, 88.4%,
      90.7% and 97.4% women had coitus during the first, second and third trimesters
      respectively, (P>0.05). Relative to pre-pregnancy behavior, 55.4%, 16.3% and
      28.3% women reported decreased, increased and unchanged coital frequency,
      respectively. Ninety six (29.6%) of the sexually active women reported having
      problems. These included vaginal soreness/pain, abdominal discomfort, bleeding,
      rupture of the membranes, urinary incontinence and vaginal dryness and itching.
      History of previous miscarriages and higher pre-pregnancy coital frequency were
      significantly associated with sexual activity during pregnancy (P <0.05). Vaginal
      intercourse is nearly universal among pregnant women attending this center with
      little variation between the trimesters. Health providers should counsel couples
      on safe coital activity during pregnancy and clear any misconceptions.

PMID- 29566325
TI  - DFT-SAPT Intermolecular Interaction Energies Employing Exact-Exchange Kohn-Sham
      Response Methods.
AB  - Intermolecular interaction energies have been calculated by symmetry-adapted
      perturbation theory based on density functional theory monomer properties (DFT
      SAPT) employing response functions from time-dependent exact-exchange (TDEXX)
      kernels. Combined with a new asymptotic correction scheme for the exchange
      correlation (xc) potentials of the monomers, which is similar in its performance
      to standard asymptotic correction methods, it is shown that this DFT-SAPT[TDEXX]
      method delivers highly accurate intermolecular interaction energies for the S22,
      S66, and IonHB benchmark databases by Hobza et al. A corresponding DFT-SAPT
      approach employing the adiabatic TDEXX kernel in the response calculations has
      also been tested. This DFT-SAPT[ATDEXX] method performs almost as well as DFT
      SAPT[TDEXX] for dispersion-dominated dimer systems but less accurately for
      hydrogen-bonded dimers. Compared to this, DFT-SAPT[TDEXX] yields a balanced
      description of the interaction energies for various interaction-type motifs,
      similar to the standard DFT-SAPT method that utilizes the ALDA xc kernel to
      compute the response functions.

PMID- 29566326
TI  - Efficient and Stable CsPbBr3 Quantum-Dot Powders Passivated and Encapsulated with
      a Mixed Silicon Nitride and Silicon Oxide Inorganic Polymer Matrix.
AB  - Despite the excellent optical features of fully inorganic cesium lead halide
      (CsPbX3) perovskite quantum dots (PeQDs), their unstable nature has limited their
      use in various optoelectronic devices. To mitigate the instability issues of
      PeQDs, we demonstrate the roles of dual-silicon nitride and silicon oxide ligands
      of the polysilazane (PSZ) inorganic polymer to passivate the surface defects and
      form a barrier layer coated onto green CsPbBr3 QDs to maintain the high
      photoluminescence quantum yield (PLQY) and improve the environmental stability.
      The mixed SiN x/SiN xO y/SiO y passivated and encapsulated CsPbBr3/PSZ core/shell
      composite can be prepared by a simple hydrolysis reaction involving the addition
      of adding PSZ as a precursor and a slight amount of water into a colloidal
      CsPbBr3 QD solution. The degree of the moisture-induced hydrolysis reaction of
      PSZ can affect the compositional ratio of SiN x, SiN xO y, and SiO y liganded to
      the surfaces of the CsPbBr3 QDs to optimize the PLQY and the stability of
      CsPbBr3/PSZ core/shell composite, which shows a high PLQY (~81.7%) with improved
      thermal, photo, air, and humidity stability as well under coarse conditions where
      the performance of CsPbBr3 QDs typically deteriorate. To evaluate the suitability
      of the application of the CsPbBr3/PSZ powder to down-converted white-light
      emitting diodes (DC-WLEDs) as the backlight of a liquid crystal display (LCD), we
      fabricated an on-package type of tricolor-WLED by mixing the as-synthesized green
      CsPbBr3/PSZ composite powder with red K2SiF6:Mn4+ phosphor powder and a
      poly(methyl methacrylate)-encapsulating binder and coating this mixed paste onto
      a cup-type blue LED. The fabricated WLED show high luminous efficacy of 138.6
      lm/W (EQE = 51.4%) and a wide color gamut of 128% and 111% without and with color
      filters, respectively, at a correlated color temperature of 6762 K.

PMID- 29566327
TI  - Synthesis of Iron Oxide Nanoclusters by Thermal Decomposition.
AB  - Herein, we report a novel one-step solvothermal synthesis of magnetite
      nanoclusters (MNCs). In this report, we discuss the synthesis, structure, and
      properties of MNCs and contrast enhancement in T2-weighted MR images using
      magnetite nanoclusters. The effect of different organic acids, used as
      surfactants, on the size and shape of MNCs was investigated. The structure and
      properties of samples were determined by magnetic measurements, TGA, TEM, HRTEM,
      XRD, FTIR, and MRI. Magnetic measurements show that obtained MNCs have relatively
      high saturation magnetization values (65.1-81.5 emu/g) and dependence of the
      coercive force on the average size of MNCs was established. MNCs were transferred
      into an aqueous medium by Pluronic F-127, and T2-relaxivity values were
      determined. T2-Weighted MR phantom images clearly demonstrated that such
      magnetite nanoclusters can be used as contrast agents for MRI.

PMID- 29566328
TI  - Sialyllactose-Modified Three-Way Junction DNA as Binding Inhibitor of Influenza
      Virus Hemagglutinin.
AB  - Sialic acid present on the cell surface is recognized by hemagglutinin (HA) on
      the influenza virus in the first step of infection. Therefore, a compound that
      can efficiently interfere with the interaction between sialic acid and HA might
      inhibit infection and allow detection of the influenza virus. We focused on the
      spatial arrangement of sialic acid binding sites on HA and developed 2,3
      sialyllactose (2,3-SL)-modified three-way junction (3WJ) DNA molecules with a
      topology similar to that of sialic acid binding sites. 3WJ DNA with three 2,3-SL
      residues on each DNA strand showed (8.0 * 104)-fold higher binding affinity for
      influenza virus A/Puerto Rico/08/34 (H1N1) compared to the 2,3-SL. This result
      indicated that the glycocluster effect due to clustering on one DNA arm and
      optimal spatial arrangement of the 3WJ DNA improved the weak interactions between
      a sialic acid and its binding site on HA. This 3WJ DNA compound has possible
      application as an inhibitor of influenza infection and for virus sensing.

PMID- 29566329
TI  - C(sp3)-H Azidation Reaction: A Protocol for Preparation of Aminals.
AB  - We report a protocol for the synthesis of N, N- and N, O-aminals via direct
      azidation of sp3 C-H bonds of substrates with an alpha-nitrogen or alpha-oxygen
      atom. A broad range of tetrahydroisoquinolines, tetrahydro-beta-carbolines, and
      cyclic benzyl ethers gave high yields under mild conditions. The protocol could
      be carried out on a gram scale without a decrease in the yield, and the aminal
      products could be readily transformed into complex aminals.

PMID- 29566330
TI  - Direct Electrochemical Sensing of Hydrogen Sulfide without Sulfur Poisoning.
AB  - An electrochemical method capable of direct, real-time detection of hydrogen
      sulfide was developed using triple pulse amperometry (TPA) to mitigate sulfur
      poisoning and its related passivation of the working electrode surface. Through
      repeated cycles of discrete potential pulses, the electrooxidation of surface
      adsorbed elemental sulfur to water-soluble sulfate ions was exploited to
      regenerate the glassy carbon electrode surface and maintain consistent sensor
      performance. Amperometric measurements and X-ray photoelectron spectroscopy
      surface analysis demonstrated that the TPA sensors provided enhanced analytical
      performance via decreased sulfur accumulation relative to low-potential (<=+0.7
      V) constant potential amperometry. Sensors operated under optimized TPA
      parameters retained high sensitivity (57.4 +/- 13.0 nA/MUM), a wide linear
      dynamic range (150 nM-15 MUM), fast response times (<10 s), and a submicromolar
      detection limit (<100 nM) upon consecutive calibration cycles. The sensitivity
      and response time achieved were comparable to or better than current
      electrochemical sensors. Moreover, the simplicity of the method eliminates the
      need for external redox mediators or semipermeable membranes.

PMID- 29566331
TI  - Heteroarylguanidines as Allosteric Modulators of ASIC1a and ASIC3 Channels.
AB  - Acid-sensing ion channels (ASICs) are neuronal Na+-selective ion channels that
      open in response to extracellular acidification. They are involved in pain, fear,
      learning, and neurodegeneration after ischemic stroke. 2-Guanidine-4
      methylquinazoline (GMQ) was recently discovered as the first nonproton activator
      of ASIC3. GMQ is of interest as a gating modifier and pore blocker of ASICs. It
      has however a low potency, and exerts opposite effects on ASIC1a and ASIC3. To
      further explore the molecular mechanisms of GMQ action, we have used the
      guanidinium moiety of GMQ as a scaffold and tested the effects of different GMQ
      derivatives on the ASIC pH dependence and maximal current. We report that GMQ
      derivatives containing quinazoline and quinoline induced, as GMQ, an alkaline
      shift of the pH dependence of activation in ASIC3 and an acidic shift in ASIC1a.
      Another group of 2-guanidinopyridines shifted the pH dependence of both ASIC1a
      and ASIC3 to more acidic values. Several compounds induced an alkaline shift of
      the pH dependence of ASIC1a/2a and ASIC2a/3 heteromers. Compared to GMQ,
      guanidinopyridines showed a 20-fold decrease in the IC50 for ASIC1a and ASIC3
      current inhibition at pH 5. Strikingly, 2-guanidino-quinolines and -pyridines
      showed a concentration-dependent biphasic effect that resulted at higher
      concentrations in ASIC1a and ASIC3 inhibition (IC50 > 100 MUM), while causing at
      lower concentration a potentiation of ASIC1a, but not ASIC3 currents (EC50 ~ 10
      MUM). In conclusion, we describe a new family of small molecules as ASIC ligands
      and identify an ASIC subtype-specific potentiation by a subgroup of these
      compounds.

PMID- 29566332
TI  - Influence of Solvent Representation on Nuclear Shielding Calculations of
      Protonation States of Small Biological Molecules.
AB  - In this study, we assess the influence of solvation on the accuracy and
      reliability of isotropic nuclear magnetic shielding calculations for amino acids
      in comparison to experimental data. We focus particularly on the performance of
      solvation methods for different protonation states, as biological molecules occur
      almost exclusively in aqueous solution and are subject to protonation with pH. We
      identify significant shortcomings of current implicit solvent models and present
      a hybrid solvation approach that improves agreement with experimental data by
      taking into account the presence of direct interactions between amino acid
      protonation state and water molecules.

PMID- 29566333
TI  - Specific Ion Effects on Protein Thermal Aggregation from Dilute Solutions to
      Crowded Environments.
AB  - We have investigated specific ion effects on protein thermal aggregation from
      dilute solutions to crowded environments. Ovalbumin and poly(ethylene glycol)
      have been employed as the model protein and crowding agent, respectively. Our
      studies demonstrate that the rate-limiting step of ovalbumin thermal aggregation
      is changed from the aggregation of unfolded protein molecules to the unfolding of
      the protein molecules, when the solution conditions are varied from a dilute
      solution to a crowded environment. The specific ion effects acting on the thermal
      aggregation of ovalbumin generated by kosmotropic and chaotropic ions are
      different. The thermal aggregation of ovalbumin molecules is promoted by
      kosmotropic anions in dilute solutions via an increase in protein hydrophobic
      interactions. In contrast, ovalbumin thermal aggregation is facilitated by
      chaotropic ions in crowded environments through accelerated unfolding of protein
      molecules. Therefore, there are distinct mechanisms causing the ion specificities
      of protein thermal aggregation between dilute solutions and crowded environments.
      The ion specificities are dominated by ion-specific hydrophobic interactions
      between protein molecules and ion-specific unfolding of protein molecules in
      dilute solutions and crowded environments, respectively.

PMID- 29566334
TI  - Anionic Annulation of 3-Cyanophthalides with Allene Carboxylates: A Carbon
      Conserved Synthesis of Naphtho[ b]furanones.
AB  - The reaction of 3-cyanophthalides with allene carboxylates in the presence of
      tBuOLi results in a tandem annulation furnishing naphtho[ b]furanones in good
      yields with no loss of carbon. The carbon economy is explained by a tandem
      process, in which the initially expelled cyanide induces the second annulation.

PMID- 29566335
TI  - Direct Molecular Dynamics Simulation of Nucleation during Supersonic Expansion of
      Gas to a Vacuum.
AB  - We develop a methodology for direct molecular-level simulation of adiabatic
      expansion of gas through a small orifice to a vacuum. The gas attains supersonic
      speeds, cools, and nucleates. The proposed approach combines equations of
      frictionless fluid dynamics with molecular dynamics simulation in an expanding
      periodic box. There are two key components of the proposed algorithm: (i) a time
      reversible integrator tailored to an expanding system, and (ii) an iterative
      procedure employed to satisfy the condition of steady flow. For a conical nozzle
      (opening angle of 60 degrees ), the simulations with argon and water vapor
      predict cluster sizes in agreement with the experiment. Clusters of irregular
      shapes observed in the experiment [J. Lengyel et al. Phys. Rev. Lett. 2014, 112,
      113401] are not reproduced. The role of friction, turbulence, and sonic boom
      originating at the sharp nozzle edge is discussed.

PMID- 29566336
TI  - A Four-Site Molecular Model for Simulations of Liquid Methanol and Water-Methanol
      Mixtures: MeOH-4P.
AB  - In this work, we present a new four-site potential for methanol, MeOH-4P, fitted
      to reproduce the dielectric constant epsilon, the surface tension gamma s, and
      the liquid density rho of the pure liquid at T = 298.15 K and p = 1 bar. The
      partial charges on each site were taken from the OPLS/2016 model with the only
      difference of putting the negative charge on the fourth site ( M) instead of on
      the O atom, as done in four-site water models. The original Lennard-Jones (LJ)
      parameters of OPLS/2016 for the methyl moiety (Me) were modified for the fitting
      of rho and gamma s, whereas the parameters of the TIP4P-FB water model were used
      for the O atom without change. Taking into account the energetic cost of the
      enhanced dipole relative to the isolated molecule, the results from simulations
      with this model showed good agreement with experiments for rho, alpha p, kappa T,
      C p, and Delta H v- l. Also, the temperature dependence of gamma s and epsilon is
      satisfactory in the interval between 260 and 360 K, and the critical point
      description is similar to that of OPLS/2016. It is shown that orientational
      correlations, described by the Kirkwood factor G k, play a prominent role in the
      appropriate description of dielectric constants in existing models;
      unfortunately, the enhancement of the dipole moment produced a low diffusion
      coefficient DMeOH; thus, a compromise was required between a good reproduction of
      epsilon and an acceptable DMeOH. The use of a fourth site resulted in a
      significant improvement for water-methanol mixtures described with TIP4P-FB and
      MeOH-4P, respectively, but required the modification of the LJ geometric
      combination rule to allow a good description of the methanol molar-fraction
      dependence of rho, epsilon, and methanol (water) diffusion coefficients DMeOH (
      DH2O) and excess volume of mixing Delta Vmix in the entire range of composition.
      The resulting free energy of hydration Delta Ghyd shows excellent agreement with
      experiments in the interval between 280 and 360 K.

PMID- 29566337
TI  - Structure-Based Optimization of Small-Molecule Inhibitors for the beta-Catenin/B
      Cell Lymphoma 9 Protein-Protein Interaction.
AB  - Structure-based optimization was conducted to improve the potency, selectivity,
      and cell-based activities of beta-catenin/B-cell lymphoma 9 (BCL9) inhibitors
      based on the 4'-fluoro- N-phenyl-[1,1'-biphenyl]-3-carboxamide scaffold, which
      was designed to mimic the side chains of the hydrophobic alpha-helical hot spots
      at positions i, i + 3, and i + 7. Compound 29 was found to disrupt the beta
      catenin/BCL9 protein-protein interaction (PPI) with a Ki of 0.47 MUM and >1900
      fold selectivity for beta-catenin/BCL9 over beta-catenin/E-cadherin PPIs. The
      proposed binding mode of new inhibitors was consistent with the results of site
      directed mutagenesis and structure-activity relationship studies. Cell-based
      studies indicated that 29 disrupted the beta-catenin/BCL9 interaction without
      affecting the beta-catenin/E-cadherin interaction, selectively suppressed
      transactivation of Wnt/beta-catenin signaling, downregulated expression of Wnt
      target genes, and inhibited viability of Wnt/beta-catenin-dependent cancer cells
      in dose-dependent manners. A comparison of the biochemical and cell-based assay
      results offered the directions for future inhibitor optimization.

PMID- 29566338
TI  - Galvanic Replacement-Driven Transformations of Atomically Intermixed Bimetallic
      Colloidal Nanocrystals: Effects of Compositional Stoichiometry and Structural
      Ordering.
AB  - Galvanic replacement reactions dictated by deliberately designed nanoparticulate
      templates have emerged as a robust and versatile approach that controllably
      transforms solid monometallic nanocrystals into a diverse set of architecturally
      more sophisticated multimetallic hollow nanostructures. The galvanic atomic
      exchange at the nanoparticle/liquid interfaces induces a series of intriguing
      structure-transforming processes that interplay over multiple time and length
      scales. Using colloidal Au-Cu alloy and intermetallic nanoparticles as
      structurally and compositionally fine-tunable bimetallic sacrificial templates,
      we show that atomically intermixed bimetallic nanocrystals undergo galvanic
      replacement-driven structural transformations remarkably more complicated than
      those of their monometallic counterparts. We interpret the versatile structure
      transforming behaviors of the bimetallic nanocrystals in the context of a unified
      mechanistic picture that rigorously interprets the interplay of three key
      structure-evolutionary pathways: dealloying, Kirkendall diffusion, and Ostwald
      ripening. By deliberately tuning the compositional stoichiometry and atomic-level
      structural ordering of the Au-Cu bimetallic nanocrystals, we have been able to
      fine-maneuver the relative rates of dealloying and Kirkendall diffusion with
      respect to that of Ostwald ripening through which an entire family of
      architecturally distinct complex nanostructures are created in a selective and
      controllable manner upon galvanic replacement reactions. The insights gained from
      our systematic comparative studies form a central knowledge framework that allows
      us to fully understand how multiple classic effects and processes interplay
      within the confinement by a colloidal nanocrystal to synergistically guide the
      structural transformations of complex nanostructures at both the atomic and
      nanoparticulate levels.

PMID- 29566339
TI  - RuO2 Thin Films Electrodeposited on Polystyrene Nanosphere Arrays: Growth
      Mechanism and Application to Supercapacitor Electrodes.
AB  - Two-dimensionally (2D) arrayed polystyrene (PS)/ruthenium oxide (RuO2) core/shell
      nanospheres are successfully prepared by the electrodeposition of RuO2
      nanoparticles on a hexagonal close-packed PS monolayer. This nanosphere structure
      is entirely different from the structure previously reported for other transition
      metal oxides electrodeposited on the PS nanosphere arrays. The different growth
      behavior is analyzed, and a possible deposition mechanism is proposed based on
      the morphological evolution and photoelectron spectroscopy measurements. As an
      electrode for supercapacitors, this 2D arrayed nanosphere structure exhibits
      superior capacitive properties such as significantly large areal capacitance,
      tight binding with current collectors, and retarded saturation of the
      capacitance, compared to a planar RuO2 film electrode.

PMID- 29566340
TI  - Reply to Soo Hoo and Esquinas: Risk Trajectories of Readmission and Death in the
      First Year after Hospitalization for Chronic Obstructive Pulmonary Disease: Don't
      Shortchange Noninvasive Ventilation.

PMID- 29566341
TI  - A microplate assay for measuring cell death in C2C12 cells.
AB  - The main goal of this study was to develop a straightforward and rapid microplate
      assay for measuring propidium iodide (PI) in C2C12 cells. The PI method has
      proven to be an efficient quantitative assay for analyzing cell viability through
      PI fluorescence analysis. Importantly, the protocol takes less than 30 min and
      the results are reproducible. C2C12 cells were exposed to an increasing
      concentration of palmitate for a period of 24 h to induce cell death, and the PI
      fluorescence increased in a concentration-dependent manner. Evaluation of
      mitochondrial function and the production of reactive oxygen species confirmed
      the deleterious effects of palmitate. Also, the microplate PI assay demonstrated
      high sensitivity, as indicated by the detection of modest fluctuations in cell
      viability in response to catalase overexpression in palmitate-treated cells. The
      microplate PI assay, therefore, offers an accurate method for use in in-vitro
      studies.

PMID- 29566342
TI  - Risk Trajectories of Readmission and Death in the First Year after
      Hospitalization for Chronic Obstructive Pulmonary Disease: Don't Shortchange
      Noninvasive Ventilation.

PMID- 29566343
TI  - Modulation of hepatic gene expression profiles by vitamin B1, vitamin B2, and
      niacin supplementation in mice exposed to acute hypoxia.
AB  - This study was aimed to observe the effects of vitamin B1, vitamin B2, and niacin
      supplementation on hepatic gene expression profiles in mice exposed to acute
      hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute
      hypoxia plus vitamin B1, vitamin B2, and niacin supplementation groups and fed
      corresponding diets for 2 weeks and then exposed to a simulated altitude of 6000
      m for 8 h. Hepatic gene expression profiles were analyzed using a microarray
      technique. Several biochemical markers were also assayed. The results showed that
      a total of 2476 genes were expressed differentially after acute hypoxia exposure
      (1508 upregulated genes and 968 downregulated genes). Compared with the acute
      hypoxia group, there were 1382 genes differentially expressed (626 upregulated
      genes and 756 downregulated genes) in the acute hypoxia plus vitamin B1, vitamin
      B2, and niacin supplementation group. Pathway analysis indicated that
      carbohydrate, lipid, and amino acid metabolism, as well as electron transfer
      chain, were improved to some extent after vitamin B1, vitamin B2, and niacin
      supplementation. Supportive results were obtained from biochemical assays. Our
      findings suggest that the supplementation of vitamin B1, vitamin B2, and niacin
      is beneficial in improving nutritional metabolism partly via gene expression
      under acute hypoxia condition.

PMID- 29566344
TI  - Diurnal variation in repeated sprint performance cannot be offset when rectal and
      muscle temperatures are at optimal levels (38.5 degrees C).
AB  - The present study investigated whether increasing morning rectal temperatures
      (Trec) to evening levels, or increasing morning and evening Trec to an "optimal"
      level (38.5 degrees C), resulting in increased muscle temperatures (Tm), would
      offset diurnal variation in repeated sprint (RS) performance in a causal manner.
      Twelve trained males underwent five sessions [age (mean +/- SD) 21.0 +/- 2.3
      years, maximal oxygen consumption (VO2max) 60.0 +/- 4.4 mL.kg-1 min-1, height
      1.79 +/- 0.06 m, body mass 78.2 +/- 11.8 kg]. These included control morning (M,
      07:30 h) and evening (E, 17:30 h) sessions (5-min warm-up), and three further
      sessions consisting of a warm-up morning trial (ME, in 39-40 degrees C water)
      until Trec reached evening levels; two "optimal" trials in the morning and
      evening (M38.5 and E38.5, in 39-40 degrees C water) respectively, until Trec
      reached 38.5 degrees C. All sessions included 3 * 3-s task-specific warm-up
      sprints, thereafter 10 * 3-s RS with 30-s recoveries were performed a non
      motorised treadmill. Trec and Tm measurements were taken at the start of the
      protocol and following the warm-up periods. Values for Trec and Tm at rest were
      higher in the evening compared to morning values (0.48 degrees C and 0.69 degrees
      C, p < 0.0005). RS performance was lower (7.8-8.3%) in the M for distance covered
      (DC; p = 0.002), average power (AP; p = 0.029) and average velocity (AV; p =
      0.002). Increasing Trec in the morning to evening values or optimal values (38.5
      degrees C) did not increase RS performance to evening levels (p = 1.000).
      However, increasing Trec in the evening to "optimal" level through a passive warm
      up significantly reduced DC (p = 0.008), AP (p < 0.0005) and AV (p = 0.007) to
      values found in the M condition (6.0-6.9%). Diurnal variation in Trec and Tm is
      not wholly accountable for time-of-day oscillations in RS performance on a non
      motorised treadmill; the exact mechanism(s) for a causal link between central
      temperature and human performance are still unclear and require more research.

PMID- 29566345
TI  - Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury.
AB  - The objective of our experiments was to identify new therapeutic strategies to
      stimulate dentin formation in an adult tooth. To address this objective, we
      evaluated dentin production in 2 acute trauma models: one involving a pulp
      exposure and the other involving a superficial dentin injury. Molecular,
      cellular, and histologic analyses revealed that in response to a severe injury,
      where the pulp is exposed to the oral cavity, cell death is rampant and the
      repair response initiates from surviving pulp cells and, to a lesser extent,
      surviving odontoblasts. When an injury is superficial, as in the case of a dentin
      injury model, then disturbances are largely confined to pulp tissue immediately
      underneath the damaged dentin tubules. We found that the pulp remained vital and
      innervated; primary odontoblasts upregulated HIF1alpha; and the rate of
      mineralization was significantly increased. A tamoxifen-inducible Axin2CreERT2/+;
      R26R mTmG/+ reporter strain was then used to demonstrate that a population of
      long-lived Wnt-responsive odontoblasts, which secreted dentin throughout the life
      of the animal, were responsible for depositing new dentin in response to a
      superficial injury. Amplifying Wnt signaling in the pulp stimulates dentin
      secretion, and in the dentin injury model, we show that a liposomal formulation
      of human WNT3A protein passes through dentinal tubules and is capable of
      upregulating Wnt signaling in the pulp. These data provide strong proof of
      concept for a therapeutic pulp-capping material to stimulate Wnt signaling in
      odontoblasts and thus improve the pulp repair response.

PMID- 29566346
TI  - Emerging Role of Extracellular Vesicles in Bone Remodeling.
AB  - Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes,
      microvesicles, and apoptotic bodies. EVs are released by most cell types, such as
      bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone
      remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and
      Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth
      factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor
      beta1) to osteoblasts and regulate bone formation. In addition, EVs can deliver
      cytokines, such as RANK (receptor activator of nuclear factor kappaB) and RANKL
      (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate
      osteoclast differentiation during bone resorption. EVs also transfer bioactive
      molecules and have targeted therapies in bone-related diseases. Moreover,
      bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight
      the emerging role of EVs in bone remodeling during physiologic and pathologic
      conditions and summarize the role of EVs in tooth development and regeneration.
      At the end of this review, we discuss the challenges of EV application in the
      treatment of bone diseases.

PMID- 29566347
TI  - Facet Annotation by Extending CNN with a Matching Strategy.
AB  - Most community question answering (CQA) websites manage plenty of question-answer
      pairs (QAPs) through topic-based organizations, which may not satisfy users' fine
      grained search demands. Facets of topics serve as a powerful tool to navigate,
      refine, and group the QAPs. In this work, we propose FACM, a model to annotate
      QAPs with facets by extending convolution neural networks (CNNs) with a matching
      strategy. First, phrase information is incorporated into text representation by
      CNNs with different kernel sizes. Then, through a matching strategy among QAPs
      and facet label texts (FaLTs) acquired from Wikipedia, we generate similarity
      matrices to deal with the facet heterogeneity. Finally, a three-channel CNN is
      trained for facet label assignment of QAPs. Experiments on three real-world data
      sets show that FACM outperforms the state-of-the-art methods.

PMID- 29566348
TI  - Optimizing the Usability of Brain-Computer Interfaces.
AB  - Brain-computer interfaces are in the process of moving from the laboratory to the
      clinic. These devices act by reading neural activity and using it to directly
      control a device, such as a cursor on a computer screen. An open question in the
      field is how to map neural activity to device movement in order to achieve the
      most proficient control. This question is complicated by the fact that learning,
      especially the long-term skill learning that accompanies weeks of practice, can
      allow subjects to improve performance over time. Typical approaches to this
      problem attempt to maximize the biomimetic properties of the device in order to
      limit the need for extensive training. However, it is unclear if this approach
      would ultimately be superior to performance that might be achieved with a
      nonbiomimetic device once the subject has engaged in extended practice and
      learned how to use it. Here we approach this problem using ideas from optimal
      control theory. Under the assumption that the brain acts as an optimal
      controller, we present a formal definition of the usability of a device and show
      that the optimal postlearning mapping can be written as the solution of a
      constrained optimization problem. We then derive the optimal mappings for
      particular cases common to most brain-computer interfaces. Our results suggest
      that the common approach of creating biomimetic interfaces may not be optimal
      when learning is taken into account. More broadly, our method provides a
      blueprint for optimal device design in general control-theoretic contexts.

PMID- 29566349
TI  - An Interneuron Circuit Reproducing Essential Spectral Features of Field
      Potentials.
AB  - Recent advances in engineering and signal processing have renewed the interest in
      invasive and surface brain recordings, yet many features of cortical field
      potentials remain incompletely understood. In the computational study that
      follows, we show that a model circuit of interneurons, coupled via both GABAA
      receptor synapses and electrical synapses, reproduces many essential features of
      the power spectrum of local field potential (LFP) recordings, such as 1/ f power
      scaling at low frequency (below 10 Hz), power accumulation in the gamma-frequency
      band (30-100 Hz), and a robust alpha rhythm in the absence of stimulation. The
      low-frequency 1/ f power scaling depends on strong reciprocal inhibition, whereas
      the alpha rhythm is generated by electrical coupling of intrinsically active
      neurons. As in previous studies, the gamma power arises through the amplification
      of single-neuron spectral properties, owing to the refractory period, by
      parameters that favor neuronal synchrony, such as delayed inhibition. This study
      also confirms that both synaptic and voltage-gated membrane currents contribute
      substantially to the LFP and that high-frequency signals such as action
      potentials quickly taper off with distance. Given the ubiquity of electrically
      coupled interneuron circuits in the mammalian brain, they may be major
      determinants of the recorded potentials.

PMID- 29566350
TI  - Hidden Quantum Processes, Quantum Ion Channels, and 1/ ftheta-Type Noise.
AB  - In this letter, we perform a complete and in-depth analysis of Lorentzian noises,
      such as those arising from [Formula: see text] and [Formula: see text] channel
      kinetics, in order to identify the source of [Formula: see text]-type noise in
      neurological membranes. We prove that the autocovariance of Lorentzian noise
      depends solely on the eigenvalues (time constants) of the kinetic matrix but that
      the Lorentzian weighting coefficients depend entirely on the eigenvectors of this
      matrix. We then show that there are rotations of the kinetic eigenvectors that
      send any initial weights to any target weights without altering the time
      constants. In particular, we show there are target weights for which the
      resulting Lorenztian noise has an approximately [Formula: see text]-type
      spectrum. We justify these kinetic rotations by introducing a quantum mechanical
      formulation of membrane stochastics, called hidden quantum activated-measurement
      models, and prove that these quantum models are probabilistically
      indistinguishable from the classical hidden Markov models typically used for ion
      channel stochastics. The quantum dividend obtained by replacing classical with
      quantum membranes is that rotations of the Lorentzian weights become simple
      readjustments of the quantum state without any change to the laboratory
      determined kinetic and conductance parameters. Moreover, the quantum formalism
      allows us to model the activation energy of a membrane, and we show that
      maximizing entropy under constrained activation energy yields the previous
      [Formula: see text]-type Lorentzian weights, in which the spectral exponent
      [Formula: see text] is a Lagrange multiplier for the energy constraint. Thus, we
      provide a plausible neurophysical mechanism by which channel and membrane
      kinetics can give rise to [Formula: see text]-type noise (something that has been
      occasionally denied in the literature), as well as a realistic and experimentally
      testable explanation for the numerical values of the spectral exponents. We also
      discuss applications of quantum membranes beyond [Formula: see text]-type -noise,
      including applications to animal models and possible impact on quantum
      foundations.

PMID- 29566351
TI  - Pattern Storage, Bifurcations, and Groupwise Correlation Structure of an Exactly
      Solvable Asymmetric Neural Network Model.
AB  - Despite their biological plausibility, neural network models with asymmetric
      weights are rarely solved analytically, and closed-form solutions are available
      only in some limiting cases or in some mean-field approximations. We found exact
      analytical solutions of an asymmetric spin model of neural networks with
      arbitrary size without resorting to any approximation, and we comprehensively
      studied its dynamical and statistical properties. The network had discrete time
      evolution equations and binary firing rates, and it could be driven by noise with
      any distribution. We found analytical expressions of the conditional and
      stationary joint probability distributions of the membrane potentials and the
      firing rates. By manipulating the conditional probability distribution of the
      firing rates, we extend to stochastic networks the associating learning rule
      previously introduced by Personnaz and coworkers. The new learning rule allowed
      the safe storage, under the presence of noise, of point and cyclic attractors,
      with useful implications for content-addressable memories. Furthermore, we
      studied the bifurcation structure of the network dynamics in the zero-noise
      limit. We analytically derived examples of the codimension 1 and codimension 2
      bifurcation diagrams of the network, which describe how the neuronal dynamics
      changes with the external stimuli. This showed that the network may undergo
      transitions among multistable regimes, oscillatory behavior elicited by
      asymmetric synaptic connections, and various forms of spontaneous symmetry
      breaking. We also calculated analytically groupwise correlations of neural
      activity in the network in the stationary regime. This revealed neuronal regimes
      where, statistically, the membrane potentials and the firing rates are either
      synchronous or asynchronous. Our results are valid for networks with any number
      of neurons, although our equations can be realistically solved only for small
      networks. For completeness, we also derived the network equations in the
      thermodynamic limit of infinite network size and we analytically studied their
      local bifurcations. All the analytical results were extensively validated by
      numerical simulations.

PMID- 29566352
TI  - Deep Semisupervised Zero-Shot Learning with Maximum Mean Discrepancy.
AB  - Due to the difficulty of collecting labeled images for hundreds of thousands of
      visual categories, zero-shot learning, where unseen categories do not have any
      labeled images in training stage, has attracted more attention. In the past, many
      studies focused on transferring knowledge from seen to unseen categories by
      projecting all category labels into a semantic space. However, the label
      embeddings could not adequately express the semantics of categories. Furthermore,
      the common semantics of seen and unseen instances cannot be captured accurately
      because the distribution of these instances may be quite different. For these
      issues, we propose a novel deep semisupervised method by jointly considering the
      heterogeneity gap between different modalities and the correlation among unimodal
      instances. This method replaces the original labels with the corresponding
      textual descriptions to better capture the category semantics. This method also
      overcomes the problem of distribution difference by minimizing the maximum mean
      discrepancy between seen and unseen instance distributions. Extensive
      experimental results on two benchmark data sets, CU200-Birds and Oxford Flowers
      102, indicate that our method achieves significant improvements over previous
      methods.

PMID- 29566353
TI  - Slowness as a Proxy for Temporal Predictability: An Empirical Comparison.
AB  - The computational principles of slowness and predictability have been proposed to
      describe aspects of information processing in the visual system. From the
      perspective of slowness being a limited special case of predictability we
      investigate the relationship between these two principles empirically. On a
      collection of real-world data sets we compare the features extracted by slow
      feature analysis (SFA) to the features of three recently proposed methods for
      predictable feature extraction: forecastable component analysis, predictable
      feature analysis, and graph-based predictable feature analysis. Our experiments
      show that the predictability of the learned features is highly correlated, and,
      thus, SFA appears to effectively implement a method for extracting predictable
      features according to different measures of predictability.

PMID- 29566354
TI  - Novel Perceptually Uniform Chromatic Space.
AB  - Chromatically perceptive observers are endowed with a sense of similarity between
      colors. For example, two shades of green that are only slightly discriminable are
      perceived as similar, whereas other pairs of colors, for example, blue and
      yellow, typically elicit markedly different sensations. The notion of similarity
      need not be shared by different observers. Dichromat and trichromat subjects
      perceive colors differently, and two dichromats (or two trichromats, for that
      matter) may judge chromatic differences inconsistently. Moreover, there is ample
      evidence that different animal species sense colors diversely. To capture the
      subjective metric of color perception, here we construct a notion of distance in
      color space based on the physiology of the retina, and is thereby individually
      tailored for different observers. By applying the Fisher metric to an analytical
      model of color representation, we construct a notion of distance that reproduces
      behavioral experiments of classical discrimination tasks. We then derive a
      coordinate transformation that defines a new chromatic space in which the
      Euclidean distance between any two colors is equal to the perceptual distance, as
      seen by one individual subject, endowed with an arbitrary number of color
      sensitive photoreceptors, each with arbitrary absorption probability curves and
      appearing in arbitrary proportions.

PMID- 29566355
TI  - Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial
      Occlusion.
AB  - The primate visual system has an exquisite ability to discriminate partially
      occluded shapes. Recent electrophysiological recordings suggest that response
      dynamics in intermediate visual cortical area V4, shaped by feedback from
      prefrontal cortex (PFC), may play a key role. To probe the algorithms that may
      underlie these findings, we build and test a model of V4 and PFC interactions
      based on a hierarchical predictive coding framework. We propose that
      probabilistic inference occurs in two steps. Initially, V4 responses are driven
      solely by bottom-up sensory input and are thus strongly influenced by the level
      of occlusion. After a delay, V4 responses combine both feedforward input and
      feedback signals from the PFC; the latter reflect predictions made by PFC about
      the visual stimulus underlying V4 activity. We find that this model captures key
      features of V4 and PFC dynamics observed in experiments. Specifically, PFC
      responses are strongest for occluded stimuli and delayed responses in V4 are less
      sensitive to occlusion, supporting our hypothesis that the feedback signals from
      PFC underlie robust discrimination of occluded shapes. Thus, our study proposes
      that area V4 and PFC participate in hierarchical inference, with feedback signals
      encoding top-down predictions about occluded shapes.

PMID- 29566356
TI  - Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure
      Suppression.
AB  - Neurostimulation is a promising therapy for abating epileptic seizures. However,
      it is extremely difficult to identify optimal stimulation patterns
      experimentally. In this study, human recordings are used to develop a functional
      24 neuron network statistical model of hippocampal connectivity and dynamics.
      Spontaneous seizure-like activity is induced in silico in this reconstructed
      neuronal network. The network is then used as a testbed to design and validate a
      wide range of neurostimulation patterns. Commonly used periodic trains were not
      able to permanently abate seizures at any frequency. A simulated annealing global
      optimization algorithm was then used to identify an optimal stimulation pattern,
      which successfully abated 92% of seizures. Finally, in a fully responsive, or
      closed-loop, neurostimulation paradigm, the optimal stimulation successfully
      prevented the network from entering the seizure state. We propose that the
      framework presented here for algorithmically identifying patient-specific
      neurostimulation patterns can greatly increase the efficacy of neurostimulation
      devices for seizures.

PMID- 29566357
TI  - Solving Constraint-Satisfaction Problems with Distributed Neocortical-Like
      Neuronal Networks.
AB  - Finding actions that satisfy the constraints imposed by both external inputs and
      internal representations is central to decision making. We demonstrate that some
      important classes of constraint satisfaction problems (CSPs) can be solved by
      networks composed of homogeneous cooperative-competitive modules that have
      connectivity similar to motifs observed in the superficial layers of neocortex.
      The winner-take-all modules are sparsely coupled by programming neurons that
      embed the constraints onto the otherwise homogeneous modular computational
      substrate. We show rules that embed any instance of the CSP's planar four-color
      graph coloring, maximum independent set, and sudoku on this substrate and provide
      mathematical proofs that guarantee these graph coloring problems will convergence
      to a solution. The network is composed of nonsaturating linear threshold neurons.
      Their lack of right saturation allows the overall network to explore the problem
      space driven through the unstable dynamics generated by recurrent excitation. The
      direction of exploration is steered by the constraint neurons. While many
      problems can be solved using only linear inhibitory constraints, network
      performance on hard problems benefits significantly when these negative
      constraints are implemented by nonlinear multiplicative inhibition. Overall, our
      results demonstrate the importance of instability rather than stability in
      network computation and offer insight into the computational role of dual
      inhibitory mechanisms in neural circuits.

PMID- 29566358
TI  - Partnering with consumers in the public reporting of quality of care: review of
      the Victorian quality of care reports.
AB  - Objective The aim of the present study was to investigate whether the content of
      annual Victorian quality of care reports had an increased consumer participation
      focus following the introduction of the National Safety and Quality Health
      Service (NSQHS) Partnering with Consumers standard.Methods A mixed-methods
      approach comprising a comparative descriptive observational study design with
      quantitative data analysis was used. Nine large Victorian metropolitan public
      health services' annual quality of care reports from 2011 and 2014 were analysed
      using a newly devised analysis framework consisting of elements of the NSQHS
      'Partnering with Consumers' standard and minimal requirements for Quality of Care
      reporting by the Department of Health and Human Services.Results Of the nine 2014
      quality of care reports, in only three were total scores higher compared with
      scores in the 2011 reports; in one of the 2014 reports, the total scores remained
      the same, and in the remaining five reports total scores were lower than in the
      2011 reports. Overall, there was an improved total score for the 2014 reports
      compared with the 2011 reports, corresponding to a higher consumer participation
      focus.Conclusion Overall, the present study demonstrated mixed findings and, in
      some cases, lower scores for the 2014 reports, which was after the introduction
      of the Partnering with Consumers NSQHS standard, compared with the 2011 reports.
      Overall, there is future scope to enhance the degree of consumer participation
      evident within the quality of care reports.What is known about the topic?
      Partnering with consumers has been associated with improved clinical outcomes,
      decreased readmission rates and rates of hospital-acquired infections, and
      improved adherence to treatment recommendations and health literacy. Engaging
      consumers has been recognised as a means to increase the accessibility and
      appropriateness of healthcare to individuals. Public reporting is a tool through
      which health services communicate with and engage their consumers in order to
      improve the quality of care they provide, and is a key element in Australia of
      the NSQHS Partnering with Consumers standard.What does the paper add? This paper
      links the principles of consumer participation with public reporting. The paper
      highlights the potential for healthcare organisations to use their public
      reporting media to engage with consumers and communicate about the quality of
      care they deliver.What are the implications for practitioners? The unexpected
      findings of a lower emphasis on consumer participation suggests the need for
      Victorian health services to review the purpose and processes for developing the
      publicly reported quality of care reports in order to improve their compliance.

PMID- 29566359
TI  - Does the professional attitude of physicians always affect their professional
      behaviour? A survey in tertiary hospitals in Nanchang City, China.
AB  - Objective Understanding the effect of professional attitude on professional
      behaviour is conducive to the development of targeted measures to promote
      professionalism. The aim of the present study was to explore the effect of
      professional attitude on professional behaviour.Methods Using a self-reported
      questionnaire, 212 physicians were surveyed using quota sampling in six tertiary
      hospitals in Nanchang City. The effect of professional attitude on professional
      behaviour was analysed through logistic regression analysis.Results Providing
      necessary care regardless of a patient's ability to pay, working on quality
      improvement initiatives, informing patients of medical errors and reporting
      incompetent colleagues had significant positive effects on corresponding
      professional behaviour (odds ratios (95% confidence intervals) 11.06 (3.78,
      32.40), 9.42 (1.93, 46.01), 4.04 (1.29, 12.63) and 5.51 (1.26, 24.08)
      respectively). However, attitudes towards minimising disparities in care,
      undergoing periodic recertification examinations and reporting medical errors did
      not significantly affect corresponding professional behaviour.Conclusions
      Professional attitude affects professional behaviour, but such an effect varies
      with different professional norms. These findings imply that improving the
      professional attitude is useful but insufficient to promote medical
      professionalism. A management system conducive to the conversion of professional
      attitude to professional behaviour should be established.What is known about the
      topic? Several studies have affirmed that Chinese physicians accept most areas of
      medical professionalism embodied in the Charter on Medical Professionalism.
      However, only a few published studies have examined the effect of professional
      attitude on professional behaviour. Understanding the effect of professional
      attitude on professional behaviour is conducive to the development of targeted
      measures to promote professionalism. The present study attempted to fill the
      current knowledge gaps.What does this paper add? The study surveyed professional
      attitudes and behaviour of Chinese physicians and explored the effects of the
      former on the latter. The study found that professional attitude affects
      professional behaviour, but such an effect varies with different professional
      norms. The results may help establish fundamental problems in the professionalism
      of physicians and in measures to promote professional behaviour not only in
      China, but also in other countries.What are the implications for practitioners?
      The implications for hospital managers and policy makers are that improving
      professional attitude is useful but insufficient to promote medical
      professionalism. A management system conducive to the conversion of professional
      attitude to professional behaviour should be established.

PMID- 29566361
TI  - Prof. Hans R. Muhlemann (1917-1997).

PMID- 29566360
TI  - The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in
      Partial Bladder Outlet Obstruction in Rats.
AB  - BACKGROUND/AIMS: Antimuscarinic agents can delay the progression of bladder
      dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship
      between muscarinic receptor activity and the bladder extracellular matrix (ECM)
      remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was
      established to explore the variation in bladder wall ECM proteins under PBOO
      conditions with antimuscarinic agent administration. METHODS: Rats were randomly
      divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red
      staining was used to examine the smooth muscle and collagen content of bladder
      samples. Gene microarray and RT-PCR were performed to survey the expression of
      ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive
      results were further evaluated by immunohistochemistry. RESULTS: Picrosirius red
      staining showed that smooth muscle volume significantly increased in the PBOO and
      PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased
      in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene
      microarray and RT-PCR revealed that none of the collagen subtypes exhibited
      significant changes after PBOO establishment and tolterodine administration.
      However, matrix metalloproteinases (MMPs) increased significantly in the PBOO
      plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of
      non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the
      expression of non-collagen ECM proteins and ECM receptors. CONCLUSIONS:
      Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly
      via MMPs, and regulated the expression of ECM proteins and receptors.

PMID- 29566362
TI  - Ethnopharmacological Study of Medicinal Plants Used for Treating Dysuria: A
      Collection from Traditional Markets in Shiraz.

PMID- 29566363
TI  - Cardiac-Specific Overexpression of Silent Information Regulator 1 Protects
      Against Heart and Kidney Deterioration in Cardiorenal Syndrome via Inhibition of
      Endoplasmic Reticulum Stress.
AB  - BACKGROUND/AIMS: Increased endoplasmic reticulum (ER) stress contributes to
      development of cardiorenal syndrome (CRS), and Silent Information Regulator 1
      (SIRT1), a class III histone deacetylase, may have protective effects on heart
      and renal disease, by reducing ER stress. We aimed to determine if SIRT1
      alleviates CRS through ER stress reduction. METHODS: Wild type mice (n=37), mice
      with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and
      corresponding controls, were randomized into four groups: sham MI (myocardial
      infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and
      MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx)
      and myocardial infarction (MI) (induced by ligation of the left anterior
      descending (LAD) coronary artery) were performed successively to establish CRS
      model. At week 8, the mice were sacrificed after sequential echocardiographic and
      hemodynamic studies, and then pathology and Western-blot analysis were performed.
      RESULTS: Neither MI nor STNx alone significantly influenced the other healthy
      organ. However, in MI groups, STNx led to more severe cardiac structural and
      functional deterioration, with increased remodeling, increased BNP levels, and
      decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups.
      Conversely, in STNx groups, MI led to renal structural and functional
      deterioration, with more severe morphologic changes, augmented desmin and
      decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx
      groups, SIRT1 knockout led to more severe cardiac structural and functional
      deterioration, with higher Masson-staining score and BNP levels, and lower EF,
      FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the
      opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater
      structural and functional deterioration, as evidenced by more severe morphologic
      changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-beta
      expression, while SIRT1 overexpression resulted in less severe morphologic
      changes and increased nephrin expression without significant influence on BUN or
      SCr levels. The SIRT1 knockout but not overexpression resulted in increased
      myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or
      overexpression resulted in increased or decreased renal expression of CHOP, Bax,
      and p53 respectively. CONCLUSIONS: Myocardial SIRT1 activation appears protective
      to both heart and kidney in CRS models, probably through modulation of ER stress.

PMID- 29566364
TI  - The Immunogenicity and Anti-Tumor Efficacy of a Rationally Designed EGFR Vaccine.
AB  - BACKGROUND/AIMS: The abnormally activated EGFR promotes tumor growth, invasion
      and metastasis. Current therapeutics targeting EGFR have markedly improved the
      clinical outcome, but they are limited in use due to transient efficacy, frequent
      administration, high cost and significant toxicity. METHODS: We rationally
      designed a multiepitope immunogen against EGFR, named as DEGFRm. The immunogen is
      composed of an epitope peptide (EGFR265-283) and the extracellular domain III
      (EGFR334-505) of mouse EGFR. EGFR265-283 is grafted onto the translocation domain
      of diphtheria toxin (DTT), and EGFR334-505 is fused to C-terminal of DTT. Next,
      the immunogenicity and anti-tumor efficacies of DEGFRm vaccine were examined in
      mouse tumor models. RESULTS: When formulated with Alum and CpG, DEGFRm vaccine
      elicits Th 1 immune responses and inhibits tumor growth in both prophylactic and
      therapeutic mouse tumor models. Moreover, the tumor microvasculature is markedly
      reduced and the tumor infiltration of CD8+ T lymphocytes is greatly enhanced.
      CONCLUSIONS: These data suggest that active immunization with DEGFRm vaccine is a
      promising strategy for therapy of various EGFR+ cancers.

PMID- 29566365
TI  - Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat
      Cardiomyocytes from Hypertrophy.
AB  - BACKGROUND: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was
      explored by investigating the expression of proteins in the phosphatidylinositol
      3-kinase (PI3K)/Akt signal pathway. METHODS: The study used a rat model of
      pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT)
      administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right
      ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in
      the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by
      quantitative (q)PCR and Western blotting. From the cellular level, we used loss
      of-function approaches to investigate the functional roles of miR-495 in cardiac
      hypertrophy induced by angiotensin II (Ang II) with immunofluorescence, qPCR, and
      Western blotting. RESULTS: The results showed that upregulation of miR-495
      markedly influenced the expression of hypertrophic markers, including the
      induction of nppa and the inhibition of myh6. In contrast, a reduction in the
      level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore,
      PTEN was identified as a potential target of miR-495 by a bioinformatics
      algorithm. Luciferase analysis and Western blot analysis confirmed that the
      contribution of miR-495 to cardiomyocyte hypertrophy may partly be through
      targeting PTEN. CONCLUSIONS: Attenuation of miR-495 derepressed PTEN to
      effectively protect rat cardiomyocytes from hypertrophy.

PMID- 29566366
TI  - Psychosocial-Stress, Liver Regeneration and Weight Gain: a Conspicuous
      Pathophysiological Triad.
AB  - Psychosocial stress alters several physiological parameters resulting in multiple
      disorders, particularly compromising the immune system thereby provoking various
      diseases including liver disorders. However, the plausible underlying mechanisms
      remain elusive. Recent literature provides mechanistic evidences of detrimental
      effects of psychosocial stress on physiology of different body organs including
      liver. The data of stress-induced pathophysiological changes in liver functions
      and obesity were systematically collected from PubMed, ScienceDirect and the Web
      of Science Databases published in English. Stress and glucocorticoids (GCs)
      control food intake and energy expenditure through appetite stimulators
      neuropeptide Y (NYP) and agouti-related protein (AgRP) in hypothalamus. Principle
      effectors of the activated hypothalamic-pituitary-adrenal (HPA) axis in response
      to psychosocial stress are proopiomelanocortin (POMC)-derived adrenocorticotropic
      hormone (ACTH) and GCs. Stress-induced GCs hyper-secretion triggers
      glucocorticoid receptor (GR)-dependent transcriptional factor, nuclear factor
      kappa B (NFkappaB), which interferes TNFalpha-IL6 and keap1-Nrf2 pathways in
      liver regeneration and obesity through fine-tuning of TNFalpha, IL6 and Nrf2
      signaling. In this review, it is contrived upon existing evidence to put forward
      a model whereby exposure to life-stress has a prominent impact over weight gain
      and can alter the regenerative mode of a damaged liver through Keap1-Nrf2 and
      TNFa-IL6 pathways.

PMID- 29566367
TI  - Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy.
AB  - BACKGROUND/AIMS: Newly identified IL-10-producing regulatory B cells (Bregs) have
      been shown to play an important role in the suppression of immune responses.
      Chronic immune activation participates in the pathogenesis of dilated
      cardiomyopathy (DCM) but whether Bregs are involved in its development remains
      unclear. We aimed to investigate the circulating frequency and function of Bregs
      in DCM. METHODS: In total, 35 DCM patients (20 men and 15 women) and 44 healthy
      controls (23 men and 21 women) were included in the experiment, and the frequency
      of Bregs was detected using flow cytometry. RESULTS: According to our results,
      the frequency of circulating IL-10-producing Bregs was significantly lower in DCM
      patients compared with healthy controls. Furthermore, the CD24hiCD27+ B cell
      subset in which IL-10-producing Bregs were mainly enriched from DCM patients
      showed impaired IL-10 expression and a decreased ability to suppress the TNF
      alpha production of CD4+CD25- Tconv cells and to maintain Tregs differentiation.
      Correlation analysis showed that the frequency of IL-10-producing Bregs and the
      suppressive function of CD24hiCD27+ B cells were positively correlated with left
      ventricular ejection fraction and negatively correlated with NT-proBNP in DCM
      patients. CONCLUSIONS: In conclusion, the reduced frequency and impaired
      functions suggest a potential role of Bregs in the development of DCM.

PMID- 29566369
TI  - Clinicopathological Characteristics, Surgical Treatments, and Survival Outcomes
      of Patients with Duodenal Gastrointestinal Stromal Tumor.
AB  - BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are rare and their
      clinicopathological features have not been completely described. In this
      retrospective study, we examined the characteristics and long-term outcomes of
      patients who underwent surgical treatment for duodenal GISTs. METHODS: We
      examined patients surgically treated for duodenal GISTs from 1999 to 2016 at the
      China National Cancer Center. We analyzed patient characteristics, treatments,
      histological examinations, and survival outcomes. RESULTS: The 52 surgeries
      performed included 14 pancreaticoduodenectomies (26.9%), 37 limited resections
      (71.2%), and one palliative bypass procedure (1.9%). No surgery-related death
      occurred. The complication rate in patients who underwent pancreaticoduodenectomy
      was slightly higher than that in patients who underwent limited resection. The 5
      year overall survival and progression-free survival rates for patients with
      duodenal adenocarcinoma were 89.1 and 72.9%, respectively. The overall survival
      and progression-free survival rates were not significantly related to surgical
      methods. Large tumor size and high mitotic rate were associated with poor overall
      survival outcomes. However, no independent factor was associated with prognosis,
      which may be due to the small sample size. CONCLUSION: The prognosis of duodenal
      gastrointestinal stromal tumors was good. Limited resection seems to be
      oncologically feasible, with outcomes being less worse than those of
      pancreaticoduodenectomy.

PMID- 29566368
TI  - The Trend of beta3-Adrenergic Receptor in the Development of Septic Myocardial
      Depression: A Lipopolysaccharide-Induced Rat Septic Shock Model.
AB  - Septic shock with low cardiac output is very common in children. However, the
      mechanism underlying myocardial depression is unclear. The role of beta3-AR in
      the development of myocardial depression in sepsis is unknown. In the present
      study, we generated an adolescent rat model of hypodynamic septic shock induced
      by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS
      to mimic myocardial depression in sepsis, which was confirmed via an in vivo left
      ventricular hemodynamic study, and measurements of contractility and the Ca2+
      transient in isolated adolescent and neonatal cardiomyocytes. After 16 h of LPS
      treatment, cultured neonatal cardiomyocytes showed a diminished Ca2+ transient
      amplitude associated with an increase in the beta3-AR level. With the addition of
      a beta3-AR agonist, the Ca2+ transient in LPS-treated neonatal rat cardiomyocytes
      gradually decreased over time; such a change was absent in cells treated with
      nitric oxide synthase (NOS) inhibitors prior to treatment with a beta3-AR
      agonist. In adolescent rats with septic myocardial depression, cardiac function
      declined as indicated by decreased MAP, dP/dtmax, and dP/dtmix for 6 h after LPS
      injection; however, the beta3-AR level first increased 2 h after LPS treatment
      and then decreased 6 h after LPS treatment in the absence of exogenous
      catecholamines. The results indicate that, in vitro, at the cellular level beta3
      AR may be involved in the development of myocardial depression (Ca2+ transient
      depression) in sepsis through NOS signaling pathways; however, in vivo, a
      complicated mechanism for modulating beta3-AR may exist.

PMID- 29566370
TI  - Dermoscopic Features of Basal Cell Carcinoma on the Lower Limbs: A Chameleon!
AB  - BACKGROUND: Lower limbs represent an uncommon location for basal cell carcinoma
      (BCC) and only few reports have described dermoscopic features of BCC in this
      body site. Since BCCs of the lower limbs frequently display nonclassic BCC
      dermoscopic criteria, they can simulate other benign or malignant lesions.
      OBJECTIVE: Our aim was to describe the dermoscopic features of BCC located on
      lower limbs and to define which criteria were more associated with their benign-
      or malignant-looking appearance. METHODS: We conducted a retrospective study
      enrolling consecutive patients with histologically confirmed BCCs of the lower
      limbs. Lesions were classified in 7 categories according to the clinical and
      dermoscopic global appearance. Clear BCC, squamous cell carcinoma (SCC) or Bowen
      disease-like, Kaposi disease-like, melanoma-like, and aspecific pattern were
      considered malignant-looking lesions; however, seborrheic keratosis-like and
      dermatofibroma-like were considered benign-looking. To define which dermoscopic
      criteria were independently associated with benign- or malignant-looking
      appearance, we conducted a multivariate logistic regression analysis. RESULTS: A
      total of 81 BCCs were enrolled: 18 (22%) were benign-looking lesions (of which 11
      were seborrheic keratosis-like and 7 dermatofibroma-like) and 63 (78%) were
      malignant-looking BCCs (of which 24 were clear-cut BCCs, 23 SCC-like, 2 Kaposi
      disease-like, 9 melanoma-like, and 5 had aspecific pattern). Multivariate
      regression analysis showed that erosions/ulceration and vessels were
      independently associated with malignant-looking appearance. The most represented
      vessels were glomerular and polymorphic, which are more frequently encountered in
      SCC, together with ulceration. CONCLUSION: BCC of the lower legs frequently
      simulates other benign or malignant lesions, with SCC being the main differential
      diagnosis.

PMID- 29566371
TI  - Influence of Visceral Fat in the Outcomes of Colorectal Cancer.
AB  - AIM: To determine the relationship of visceral fat (VF) with the surgical outcome
      of the patients with colorectal cancer (CRC) submitted to curative surgery.
      METHODS: Retrospective analysis of all patients submitted to CRC surgery during 3
      years with a minimum of 5 years of follow-up. We assessed the length of hospital
      stay, complications, pathologic reports, surgical re-interventions and hospital
      re-admissions, relapses, survival time and disease-free time. VF was calculated
      based on patients' pre-operative CT-scan. The patients were divided into
      quartiles according to the VF area. Linear regression models and logistic
      regression models were used to establish a relationship between VF and all data
      collected. RESULTS: The study included 199 patients (129 with colon cancer [CC]
      and 70 with rectal cancer). The average area of VF was 115.7 cm2. Patients with
      CRC revealed a direct relationship between VF and postoperative complications (p
      = 0.043), anastomotic leakage (p = 0.009) and re-operation (p = 0.005). The
      subgroup of patients with CC had an inverse association between VF and lymph
      nodes harvested (p = 0.027). Survival analyses did not reveal significant
      differences. CONCLUSION: VF has an influence on postoperative complications,
      anastomotic leakage and re-operation. A negative influence of VF on lymph nodes
      harvested was observed on CC patients.

PMID- 29566372
TI  - Prevalence, Recognition, and Treatment of Dementia in Assisted Living Facilities.
AB  - BACKGROUND/AIMS: Dementia and psychiatric disorders are common in assisted living
      facilities (ALFs) and have suboptimal rates of recognition and treatment.
      Therefore, we aimed to obtain a direct estimate of the prevalence of cognitive
      impairment and especially dementia among residents of ALFs in western Slovakia
      and their rates of primary recognition and adequate treatment. METHODS: We
      conducted two cross-sectional studies. Ten ALFs within the city of Bratislava
      were chosen for the study in 2004, and again in 2011. A total of 866 residents in
      ALFs were examined in 2004, and 821 residents in ALFs were examined in 2011. The
      rate and characterization of dementia, its primary recognition and adequate
      treatment were investigated in both cross-sectional studies. RESULTS: In 2004,
      57% of the participants had dementia. Only 7.2% of the participants with probable
      Alzheimer disease were treated with acetylcholinesterase inhibitors. In 2011, we
      observed a significant improvement in primary diagnostics and therapy. 66.9% of
      the cases of dementia were adequately evaluated, and 52.1% were adequately
      treated. CONCLUSION: Cognitive deficit and dementia are significantly
      underdiagnosed and undertreated in assisted living settings. In the second cross
      sectional study we detected significant but not complete improvement in the
      primary recognition and adequate therapy of dementia.

PMID- 29566373
TI  - Reclassification of Chronic Kidney Disease Stage, Eligibility for Cystatin-C and
      Its Associated Costs in a UK Primary Care Cohort.
AB  - BACKGROUND AND AIMS: Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)
      estimations of glomerular filtration rate (eGFR), compared to modification of
      diet in renal disease (MDRD), have superior performance in predicting renal,
      cardiovascular and mortality events. Cystatin-C further improves prediction. Our
      primary aim was to assess the change in prevalence and classification of CKD in
      converting from MDRD to CKD-EPI in an unselected primary care CKD population. Our
      secondary aims were to determine the eligibility for cystatin-C testing based on
      National Institute for Health and Care Excellence guidance and the associated
      costs. METHODS: eGFR data from an unselected UK primary care CKD cohort was
      studied to assess reclassification of CKD stages from MDRD to CKD-EPI,
      suitability for cystatin-C testing and its associated cost. RESULTS: A total
      number of 24,660 individuals had >=2 MDRD eGFR results <60 mL/min/1.73 m2 >3
      months apart (7.0% of adult population). The mean age was 75.2 (SD 11.4 years)
      with 15,265 (61.9%) females. Mean eGFR was 2.88 mL/min/1.73 m2 lower with CKD-EPI
      eGFR versus MDRD eGFR (49.7 vs. 46.8, t test p < 0.0001, 95% CI 2.85-2.91). 12.0%
      of individuals were re-categorised to a more or less advanced CKD stage, and 1.3%
      to a less advanced stage. The percentage of the population categorised as 3a-A1
      CKD-EPI and therefore potentially suitable for cystatin-C was 2.8%. The estimated
      initial cost is ?67.5 (L57.2) million with annual costs of ?2.7 (L2.3) million
      for the United Kingdom. CONCLUSIONS: The mean eGFR was lower with the CKD-EPI
      formula and individuals were more likely to be reclassified to more advanced CKD.
      This may be related to the higher mean age of this unselected population compared
      to previous studies. Refinements of eGFR formulae, CKD definitions and cystatin-C
      eligibility in unselected populations are required.

PMID- 29566374
TI  - Screening for Dysphagia: Perspectives and Practices of Speech and Language
      Therapists in the Republic of Ireland.
AB  - OBJECTIVE: Clinical guidelines place considerable emphasis on early swallow
      screening, as it has significant impact on patient outcomes. This study aims to
      examine perspectives and practices of speech and language therapists (SLTs) in
      the Republic of Ireland on swallow screening, exploring challenges in screening
      methods to improve practice and facilitate research. METHODS: An 18-item web
      based survey was devised targeting SLTs working in dysphagia in Republic of
      Ireland. Perspectives were sought on definitions of screening, models of
      practice, tests used, and factors influencing decision-making. RESULTS: Fifty
      eight SLTs responded, representing a cross section of clinical settings,
      populations, and experience. Screening tests most frequently employed were
      personal screening tests (80%). Important considerations reported in test
      selection were patient safety (100%), ease of use (97%), staffing (97.5%), and
      diagnostic accuracy (97.5%). Perceived challenges were staff training associated
      with screening. CONCLUSIONS: It is concerning that while diagnostic accuracy was
      recognised as important, most respondents used tests lacking in diagnostic
      accuracy. While the survey response rate was low, it is hypothesised that
      findings reflect practice. There is a need for SLTs to equip themselves with the
      skills to discern which screening test is most diagnostically accurate for
      clinical populations with further research to improve practice.

PMID- 29566375
TI  - Long-Term Results of Vitrectomy for Macular Holes after Failure of Vitreolysis.
AB  - PURPOSE: Ocriplasmin injection may close some small-to-medium macular holes
      associated with vitreoretinal traction. If the treatment fails, does vitrectomy
      and gas injection yield the same results as primary surgery? MATERIAL AND
      METHODS: We report a retrospective case series study of 3 eyes of 3 consecutive
      patients operated on a few months after initial intravitreal injection of
      ocriplasmin and enlargement of the macular hole. The minimal follow-up period
      after surgery was 18 months. RESULTS: Surgery was uneventful in all cases.
      Vitrectomy, internal limiting membrane peeling, and gas injection allowed closing
      of the 3 macular holes with a progressive improvement in visual acuity over time.
      Before ocriplasmin injection, visual acuity ranged from 20/60 to 20/32, after
      failed ocriplasmin injection from 20/80 to 20/40, and at the final follow-up
      after 18 months from 20/32 to 20/25. CONCLUSION: Vitrectomy with internal
      limiting membrane peeling leads to closure of macular holes even in cases of
      prior failure to close them by ocriplasmin injection.

PMID- 29566376
TI  - Neurosyphilis with Bilateral Optic Perineuritis in an Immunocompetent Patient.

PMID- 29566377
TI  - The Primitive Palmomental Reflex in Amyotrophic Lateral Sclerosis.
AB  - BACKGROUND AND PURPOSE: The palmomental reflex (PMR) is a primitive reflex that
      might be released due to inhibition in adulthood. It has been associated with
      several neurodegenerative conditions. The aim of the present study was to
      evaluate the frequency of PMR in amyotrophic lateral sclerosis (ALS). PATIENTS
      AND METHODS: Non-demented ALS patients (n = 179) were recruited. Two groups of
      disease controls were enrolled: (a) non-demented patients with other neurological
      disorders (NC; n = 86, mean age 60 +/- 14 years); (b) healthy subjects, healthy
      controls (HC; n = 175, mean age 61 +/- 12 years). PMR was elicited by a brisk
      stroke along the thenar eminence of the right hand with a key or a pen. RESULTS:
      The PMR could be elicited in 46% of the ALS patients, compared to 29% of NC and
      16% of HC (p < 0.001). A multivariate analysis showed that bulbar-onset and
      female gender are associated with an increased risk of PMR. CONCLUSION: We
      demonstrate a higher frequency of the PMR in ALS patients compared to NC or HC.
      Its expression increases with age, being higher in bulbar-onset patients. Given
      that the reflex circuit is located in the brain stem, its release due to
      inhibition might be associated to the presence of a cortico-bulbar tract
      dysfunction in ALS.

PMID- 29566378
TI  - Adrenal Insufficiency, Sex Reversal, and Angelman Syndrome due to Uniparental
      Disomy Unmasking a Mutation in CYP11A1.
AB  - BACKGROUND/AIMS: Cholesterol side-chain cleavage enzyme (P450scc) deficiency is a
      rare genetic disorder causing primary adrenal insufficiency with or without a
      46,XY disorder of sexual development (DSD). Herein, we report a case of the
      combination of primary adrenal insufficiency, a DSD (testes with female external
      genitalia in a setting of a 47,XXY karyotype), and Angelman syndrome. METHODS:
      Comprehensive genetic analyses were performed, including a single nucleotide
      polymorphism microarray and whole-exome sequencing. In vitro studies were
      performed to evaluate the pathogenicity of the novel mutation that was identified
      by whole-exome sequencing. RESULTS: The patient was found to have segmental
      uniparental disomy (UPD) of chromosome 15 explaining her diagnosis of Angelman
      syndrome. Whole-exome sequencing further revealed a novel homozygous intronic
      variant in CYP11A1, the gene encoding P450scc, found within the region of UPD. In
      vitro studies confirmed that this variant led to decreased efficiency of CYP11A1
      splicing. CONCLUSION: We report the first case of the combination of 2 rare
      genetic disorders, Angelman syndrome, and P450scc deficiency. After 20 years of
      diagnostic efforts, significant advances in genetic diagnostic technology allowed
      us to determine that these 2 disorders originate from a unified genetic etiology,
      segmental UPD unmasking a novel recessive mutation in CYP11A1.

PMID- 29566379
TI  - Apabetalone Mediated Epigenetic Modulation is Associated with Favorable Kidney
      Function and Alkaline Phosphatase Profile in Patients with Chronic Kidney
      Disease.
AB  - BACKGROUND/AIMS: The association between serum alkaline phosphatase (ALP) with
      adverse cardiovascular outcomes, in Chronic Kidney Disease (CKD) patients has
      previously been reported and may be a result of increased vascular calcification
      and inflammation. Here we report, for the first time, the effects of
      pharmacologic epigenetic modulation on levels of ALP and kidney function via a
      novel oral small molecule BET inhibitor, apabetalone, in CKD patients. METHODS: A
      post-hoc analysis evaluated patients with estimated glomerular filtration rate
      (eGFR) <60 mL/min/1.73m2, who participated in the apabetalone phase 2 randomized
      controlled trials (SUSTAIN and ASSURE). 48 CKD subjects with a history of
      cardiovascular disease (CVD) were treated with 100mg twice-daily of 24 and 26
      weeks of apabetalone or placebo. ALP and eGFR were measured prior to
      randomization and at final visits. RESULTS: Patients who received apabetalone
      (n=35) versus placebo (n=13) over 6 months showed significantly (p=0.02) lowered
      serum ALP -14.0% (p<0.0001 versus baseline) versus -6.3% (p=0.9 versus baseline).
      The eGFR in the apabetalone group increased by 3.4% (1.7 mL/min/1.73 m2) (p=0.04
      versus baseline) and decreased by 5.8% (2.9 mL/min/1.73 m2) (p=0.6 versus
      baseline) in the placebo group. Apabetalone was well tolerated. CONCLUSION: A
      post-hoc analysis of CKD subjects from the SUSTAIN and ASSURE randomized
      controlled trials demonstrated favorable effects of apabetalone on ALP and eGFR,
      and generated the hypothesis that epigenetic modulation by BET inhibition may
      potentially offer a novel therapeutic strategy to treat CVD and progressive
      kidney function loss in CKD patients. This is being examined in the phase III
      trial BETonMACE.

PMID- 29566380
TI  - Resting Heart Rate Is Not Associated with Cognitive Function.
AB  - AIMS: In order to examine the hypothesis that elevated resting heart rate (RHR)
      is associated with impaired cognitive score, we investigated the relationship
      between RHR and cognitive score in middle-aged, elderly and old Danish subjects
      from the general population. METHODS: Composite cognitive scores derived from the
      result of 5 age-sensitive cognitive tests for a total of 7,002 individuals
      (Middle-aged Danish twin: n = 4,132, elderly Danish twins: n = 2,104 and Danish
      nonagenarian: n = 766) divided according to RHR and compared using linear
      regression models adjusted for sex, age, previous heart conditions and
      hypertension. RHR was assessed by palpating radial pulse. Genetic and shared
      environmental confounding was addressed in intrapair analyses of 2,049 twin
      pairs. RESULTS: In unadjusted multivariate models and in multivariable models
      adjusting for age, sex, heart conditions and hypertension, RHR was not associated
      with cognitive function. Furthermore, the intrapair analyses showed that RHR was
      not associated with cognitive score testing within twin pairs, as measured by the
      proportion of twin pairs in which the twin with higher RHR also was the twin with
      the lowest composite cognitive score (1,049 pairs of 2,049 pairs [51% (95% CI 49
      53), p < 0.289]). CONCLUSION: While elevated RHR has been shown to be associated
      with adverse health events and poor fitness level, RHR has no relation to
      cognitive function in the general population.

PMID- 29566381
TI  - The Research Cycle: Improving Care and Outcomes for Newborn Infants.
AB  - Ensuring that policies and practice in perinatal care are informed by evidence
      from high-quality research is fundamental to improving outcomes for newborn
      infants and their families. Effective interventions in the perinatal period can
      have a life-long impact disproportionate to their costs. Many of the major
      advances in care that have transformed outcomes for preterm and sick newborn
      infants have been informed by empirical and applied health research. Conversely,
      there are examples of life-long adverse consequences for infants and families
      that are a legacy of practices based on poor-quality evidence. The challenge in
      the 21st century is to maintain the trajectory of improvements in care and
      outcomes. This will most likely be achieved via marginal gains from new or
      improved care practices underpinned by a range of research approaches, from
      preclinical and laboratory-based empirical studies that uncover pathogenic
      pathways or therapeutic mechanisms, to large-scale, applied research such as
      multicentre, randomised controlled trials. This will involve the coordination and
      collaboration of research efforts globally. Strategies to develop and prioritise
      research questions need to involve parents and families. Given the context in
      which much perinatal research is conducted, particularly in emergency situations
      around the time of birth, robust and transparent ethics and governance frameworks
      are essential to maintain the trust and engagement of communities. An ethical
      imperative exists to ensure that research output is disseminated effectively, and
      that effective and cost-effective interventions are implemented and integrated
      within a cycle that audits and benchmarks good practice and outcomes, and informs
      research evidence-based continuous quality improvement. This is the first in a
      series of articles on research methodology in neonatal medicine to be published
      in Neonatology, in response to a request from trainee researchers. We introduce
      the series by describing the research cycle, in particular how it is applied in
      neonatal medicine. Subsequent articles will cover translational research,
      clinical trials, diagnostic tests, global challenges, and the ethical issues
      relating to neonatal/perinatal research.

PMID- 29566382
TI  - Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese
      Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics
      Proteins.
AB  - BACKGROUND: We have previously reported that testosterone deprivation at a very
      young age accelerated, but did not aggravate, left-ventricular (LV) dysfunction
      in obese insulin-resistant rats. However, the effects of testosterone deprivation
      during adulthood on LV function in obese insulin-resistant rats remains unclear.
      We hypothesized that testosterone deprivation aggravates LV dysfunction and
      cardiac autonomic imbalance via the impairment of cardiac mitochondrial function
      and dynamics proteins, a reduction in insulin receptor function, and an increase
      in apoptosis in obese insulin-resistant rats. METHODS: Male rats were fed on
      either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. They were then
      subdivided into 2 groups: sham operation (NDS, HFS) and orchiectomy (NDO, HFO).
      Metabolic parameters, blood pressure, heart rate variability (HRV), and LV
      function were determined at baseline and before and after orchiectomy.
      Mitochondrial function and dynamics proteins, insulin signaling, and apoptosis
      were determined 12 weeks postoperatively. RESULTS: HFS rats exhibited obese
      insulin resistance, depressed HRV, and LV dysfunction. In HFO rats, systolic
      blood pressure was increased with more excessive depression of HRV and increased
      LV dysfunction, compared with HFS rats. These adverse cardiac effects were
      consistent with markedly increased mitochondrial dysfunction, reduced
      mitochondrial complex I and III proteins, reduced mitochondrial fusion proteins,
      and increased apoptosis, compared with HFS rats. However, testosterone
      deprivation did not lead to any alteration in the insulin-resistant condition in
      HFO rats, compared with HFS rats. CONCLUSION: We concluded that testosterone
      deprivation during adulthood aggravated the impairment of mitochondrial function,
      mitochondrial respiratory complex, mitochondrial dynamics proteins, and
      apoptosis, leading to LV dysfunction in obese insulin-resistant rats.

PMID- 29566383
TI  - Gastritis Can Cause and Trigger Chronic Spontaneous Urticaria Independent of the
      Presence of Helicobacter pylori.
AB  - BACKGROUND/AIM: In chronic spontaneous urticaria (CSU), Helicobacter pylori (HP)
      has been discussed as a cause, but it is unknown whether the bacterium itself or
      concomitant inflammation is causing the urticaria. Our aim was to investigate HP
      and upper gastrointestinal lesions as signs of inflammation independently of each
      other in the pathogenesis of CSU. METHODS: A total of 36 prospectively enrolled
      CSU patients from Moscow were investigated by gastroscopy and screened for the
      presence of HP and/or upper gastrointestinal lesions. Those having a positive
      result were treated according to the Maastricht III recommended guidelines for
      eradication therapy, and success was assessed by a follow-up gastroscopy.
      Simultaneously, the activity of CSU was measured before and after therapy of the
      gastrointestinal condition. RESULTS: HP was observed in 26 of the 36 patients.
      Erosions or ulcers were found in 18 of the 36 patients, 14 of whom were also
      positively tested for HP. There was a significant difference in improvement of
      urticarial symptoms between those who succeeded in healing the erosions and those
      who did not succeed (p < 0.01) independent of the presence of HP. No significant
      difference in symptom relief was observed between those who had successful
      eradication and those in whom HP eradication failed. CONCLUSIONS: Upper
      gastrointestinal inflammatory disorders can cause CSU and trigger exacerbations
      independently of HP. This might imply that also in HP-positive patients,
      urticaria is not based on an immunological reaction against the germ but rather
      on the underlying inflammation. These findings also strengthen the importance of
      a gastroenterological workup of patients with CSU.

PMID- 29566384
TI  - Parkinson's Disease, Melanoma, and Keratinocyte Carcinoma: A Population-Based
      Study.
AB  - BACKGROUND: The association between Parkinson's disease (PD) and melanoma is well
      recognized, but its relationship with non-melanoma skin cancers has not been
      studied in depth. OBJECTIVE: To assess the relationship between PD, and risk of
      melanoma and keratinocyte carcinoma: squamous cell carcinoma (SCC) and basal cell
      carcinoma (BCC). METHODS: This historical cohort study used the data of 1.2
      million adult members of a large health organization between 2000 and 2015.
      Individuals who were diagnosed with PD anytime between 2000 and 2010 were
      retrospectively followed until 8/2016 for incidence of SCC, BCC, or melanoma
      identified from physician diagnoses and pathology reports. RESULTS: The PD cohort
      included 7,727 patients (mean [SD] age = 69.9 [14.8 years]) among the 1,251,695
      study population. During follow-up, a total of 4,553, 32,069, and 4,015 cases of
      BCC, SCC, and melanoma were identified in the study population respectively.
      Multivariable models revealed that older age, male sex, never smoking, and
      residence in southern Israel and actinic keratosis were associated with an
      increased risk of both BCC and SCC. PD patients in the age range 45-64 and 65-84
      years at baseline had an OR of 2.11 (95% CI 1.40-3.18) and 1.52 (95% CI 1.21
      1.91) for BCC respectively. Weak or no associations were calculated for melanoma
      or SCC. CONCLUSIONS: We report a positive relationship between PD and risk of
      BCC. These results should stimulate greater awareness on the part of healthcare
      providers to the increased risk of BCC in PD patients.

PMID- 29566385
TI  - A Comprehensive Assessment of the Role of miRNAs as Biomarkers in
      Gastroenteropancreatic Neuroendocrine Tumors.
AB  - BACKGROUND/AIMS: A key issue in neuroendocrine neoplasia management is the
      identification of blood signatures that specifically define the activity of a
      cancer or local tumor microenvironment. MicroRNAs (miRNAs) may represent such a
      candidate. To evaluate their clinical utility as biomarkers in
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we assessed their
      expression in tissue and blood. METHODS: A systematic review of PubMed was
      undertaken to identify studies investigating miRNAs in GEP-NETs and their utility
      as blood or tissue biomarkers. RESULTS: Twenty-two studies using a range of
      methodologies with different normalization protocols were identified: tumor -
      gastric NET type 1 (n = 1 study: MiR-222, regulates p27KIP1), pancreatic (n = 6:
      MiR-21 [inflammatory marker, oncogene] and MiR-144 [PI3K/AKT signaling], both up-
      and downregulated depending on the method), small intestinal (n = 7: no
      consistent signature), and colorectal (n = 3: no consistent signature); blood -
      gastric NET type 1 (n = 1: MiR-222), pancreatic (n = 3: MiR-21), and small
      intestinal (n = 3: no consistent signature). The studies all included
      heterogeneous cohorts, were insufficiently powered, and utilized different
      methodologies, and age- and gender-matched controls were not used. Different
      miRNA isolation methods and detection protocols resulted in inconsistent
      expression comparing tumor and blood. A scientific discrepancy was the
      downregulated expression of some circulating candidates compared to tissue
      levels, suggesting methodological issues or physiological responses to the tumor.
      Both are of concern in defining the biometrics of a marker. CONCLUSIONS: A
      potential biomarker for GEP-NETs included MiR-21 (small bowel and pancreas), but
      this epithelial tumor marker requires prospective validation. Overall,
      significant scientific investigation remains to identify and demonstrate
      neuroendocrine specificity and to validate candidate miRNA biomarkers.

PMID- 29566386
TI  - Occipital Condyle Fracture Extending to the Inferior Part of the Clivus.
AB  - Although rarely reported in the literature, serious occipital and condylar
      fractures have been diagnosed more often with the widespread use of computed
      cranial tomography in traumas. In this paper, a 16-year-old female with a left
      occipital fracture extending from the left occipital condyle anterior of the
      hypoglossal canal to the inferior part of the clivus is presented. The fracture
      which had caused a neurological deficit was cured with conservative treatment.
      For delayed hypoglossal nerve paralysis due to swelling within the canal,
      methylprednisolone was started, and a complete cure was attained in about 10
      days. Traumatic damage of bony structures of the condyle and clivus at the
      junction of many vital nerves, vessels, and ligaments may lead to traumatic
      deficit and death.

PMID- 29566387
TI  - Spectral-Domain Optical Coherence Tomography-Driven Treat-and-Extend and Pro Re
      Nata Regimen in Patients with Macular Oedema due to Retinal Vein Occlusion: 24
      Month Evaluation and Outcome Predictors.
AB  - PURPOSE: To analyse the efficacy and outcome predictors of ranibizumab using a
      spectral-domain optical coherence tomography (SD-OCT)-driven treat-and-extend
      regimen (TER) versus SD-OCT-driven pro re nata regimen (PRN) in patients with
      cystoid macular oedema (CME) due to branch or central retinal vein occlusion
      (BRVO, CRVO). METHODS: Retrospective, consecutive case series. Evaluation
      included best corrected visual acuity (BCVA), morphological parameters on SD-OCT,
      and treatment frequency. RESULTS: From baseline to months 12, 18, and 24, BCVA
      improved by 16.6 +/- 13.1, 15.5 +/- 14.4, and 16.6 +/- 15.8 letters,
      respectively, in TER (n = 45), compared to 11.3 +/- 17.0, 11.0 +/- 15.0, and 10
      +/- 20.5 letters in PRN (n = 31) (p = 0.152, p = 0.237, p = 0.172). The mean
      reduction in central retinal thickness was -261 +/- 189, -272 +/- 188, and -264
      +/- 158 MUm, respectively, in TER, compared to -130 +/- 196, -140 +/- 210, and 
      166 +/- 207 MUm in PRN (p = 0.006, p = 0.017, p = 0.064). 59% (53%) of TER and
      22% (17%) of PRN patients showed no intra- or subretinal fluid on SD-OCT at 12
      (24) months. Using TER, the maximum recurrence-free treatment interval increased
      from 8.9 +/- 2.3 weeks at 12 months to 9.8 +/- 2.3 and 10.5 +/- 2.7 weeks at 18
      and 24 months, respectively. The number of injections was significantly higher in
      the TER than in the PRN group. CONCLUSIONS: In CME, due to BRVO/CRVO, TER
      provides better morphological outcome using more injections than PRN.

PMID- 29566388
TI  - Punicalagin and (-)-Epigallocatechin-3-Gallate Rescue Cell Viability and
      Attenuate Inflammatory Responses of Human Epidermal Keratinocytes Exposed to
      Airborne Particulate Matter PM10.
AB  - BACKGROUND/AIMS: Airborne particulate matter with a diameter of < 10 um (PM10)
      causes oxidative damage, inflammation, and premature skin aging. In this study,
      we evaluated whether polyphenolic antioxidants attenuate the inflammatory
      responses of PM10-exposed keratinocytes. METHODS: Primary human epidermal
      keratinocytes were exposed in vitro to PM10 in the absence or presence of
      punicalagin and (-)-epigallocatechin-3-gallate (EGCG), which are the major
      polyphenolic antioxidants found in pomegranate and green tea, respectively.
      Assays were performed to determine cell viability, production of reactive oxygen
      species (ROS), and expression of NADPH oxidases (NOX), proinflammatory cytokines,
      and matrix metalloproteinase (MMP)-1. RESULTS: PM10 decreased cell viability and
      increased ROS production in a dose-dependent manner. It also increased the
      expression levels of NOX-1, NOX-2, tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, IL-6, IL-8, and MMP-1. Punicalagin was not cytotoxic up
      to 300 MUM, and (-)-EGCG was cytotoxic above 30 MUM, respectively. Further,
      punicalagin (3-30 MUM) and EGCG (3-10 MUM) rescued the viability of PM10-exposed
      cells. They also attenuated ROS production and the expression of NOX-1, NOX-2,
      TNF-alpha, IL-1beta, IL-6, IL-8, and MMP-1 stimulated by PM10. CONCLUSIONS: This
      study demonstrates that polyphenolic antioxidants, such as punicalagin and (-)
      EGCG, rescue keratinocyte viability and attenuate the inflammatory responses of
      these cells due to airborne particles.

PMID- 29566389
TI  - Amyloid Deposits and Idiopathic Normal-Pressure Hydrocephalus: An 18F-Florbetaben
      Study.
AB  - BACKGROUND: The first aim of our study was to determine whether cortical 18F
      florbetaben retention was different between healthy controls and idiopathic
      normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate
      whether there were any relationships between 18F-florbetaben retention and either
      hippocampal volume or clinical symptoms in INPH patients. METHODS: Seventeen
      patients diagnosed with INPH and 8 healthy controls underwent studies with
      magnetic resonance imaging and 18F-florbetaben positron emission tomography
      imaging. RESULTS: Automated region-of-interest analysis showed significant
      increases in 18F-florbetaben uptake in several brain regions in INPH patients
      compared to control subjects, with especially remarkable increases in the frontal
      (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the
      INPH group, right hippocampal volume was found to be negatively correlated with
      right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination
      scores negatively correlated with right occipital 18F-florbetaben retention.
      Higher 18F-florbetaben retention correlated significantly with a higher Clinical
      Dementia Rating Scale score in the right occipital cortex. CONCLUSIONS: Our
      results indicate that INPH might be a disease exhibiting a characteristic pattern
      of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal
      cortex may be related to hippocampal neuronal degeneration. Our findings may also
      help us understand the potential pathophysiology of cognitive impairments
      associated with INPH.

PMID- 29566390
TI  - Cognitive Emotion Regulation Strategies in Borderline Personality Disorder:
      Diagnostic Comparisons and Associations with Potentially Harmful Behaviors.
AB  - BACKGROUND: Although difficulties in emotion regulation (ER) are considered a
      core feature of borderline personality disorder (BPD), the specific strategies
      that individuals with BPD most commonly use, their diagnostic specificity, and
      their associations with harmful behaviors have not been firmly established.
      SAMPLING AND METHODS: Individuals with BPD (n = 30), mixed anxiety and/or
      depressive disorders (MAD; n = 30), and healthy controls (HC; n = 32) completed
      questionnaires assessing both cognitive ER strategies (e.g., cognitive
      reappraisal) and potentially harmful behaviors that individuals might use to
      regulate their emotions (e.g., self-injury). RESULTS: BPD subjects endorsed more
      maladaptive cognitive ER strategies and fewer adaptive strategies compared to HC.
      Compared to MAD subjects, BPD individuals endorsed more maladaptive cognitive ER
      strategies, but only when those with subthreshold symptoms in the MAD group were
      excluded. BPD also endorsed engaging in potentially harmful behaviors more often
      than both HC and MAD. Discriminant analysis revealed that MAD endorsed lower
      rates of problem-solving and cognitive reappraisal compared to both HC and BPD.
      Higher maladaptive and lower adaptive ER strategies were associated with higher
      rates of potentially harmful behaviors, although the specific strategies differed
      for MAD versus BPD. CONCLUSIONS: BPD and MAD endorse cognitive ER strategies with
      a comparable frequency, although BPD subjects engage in potentially harmful
      behaviors more often. Subthreshold BPD symptoms may also affect rates of ER
      strategy use in individuals with other mental disorders.

PMID- 29566391
TI  - Psychopathological Symptoms and Satisfaction with Mental Health in Patients with
      Schizophrenia.
AB  - BACKGROUND: The patient's view of their mental health is a central aspect in
      research and practice. Yet, little is known about which psychopathological
      symptoms are linked with patients' satisfaction with their mental health. We
      aimed to identify these symptoms in patients with schizophrenia. METHODS: An
      individual patient data meta-analysis was conducted with data from 2,488 patients
      from 8 independent studies. Satisfaction with mental health was rated on a 7
      point scale, and symptoms were observer-rated using identical items from the
      Brief Psychiatric Rating Scale and the Positive and Negative Symptom Scale. Mixed
      multilevel univariate followed by multivariate regression models were used to
      identify symptoms associated with satisfaction with mental health. RESULTS: In
      univariate regressions, all subscales - not age and gender - were associated with
      mental health satisfaction. In the multivariate regression, only affective and
      negative symptoms were significantly associated with a lower satisfaction with
      mental health, explaining 22.5% of the variance. CONCLUSIONS: Observer-rated
      psychopathological symptoms are linked to patients' mental health satisfaction.
      In addition to affective symptoms - which are commonly negatively linked with
      satisfaction ratings - a higher level of negative symptoms makes patients less
      satisfied with their mental health, whilst positive and other symptoms do not
      influence mental health satisfaction.

PMID- 29566392
TI  - Dual p16 and Ki-67 Expression in Liquid-Based Cervical Cytological Samples
      Compared to Pap Cytology Findings, Biopsies, and HPV Testing in Cervical Cancer
      Screening: A Diagnostic Accuracy Study.
AB  - OBJECTIVE: Our objective was to verify the sensitivity and specificity of dual
      immunocytochemistry staining for p16 and Ki-67 in liquid-based samples (the
      "dual" assay) for cervical lesion screening, compared to biopsy findings and
      human papillomavirus (HPV) DNA molecular detection. STUDY DESIGN: Sensitivity,
      specificity, and positive (PPV) and negative (NPV) predictive values for the
      "dual immunocytochemistry assay" were calculated and compared to
      histopathological results and to high-risk HPV DNA detection in adult women or
      teenagers submitted to cervical cancer screening. RESULTS: A total of 151 women
      were included. The majority (96.2%) of those with negative dual assay results had
      lower biopsy grades (p < 0.001). Women with cytology results suggestive of
      cervical cancer had positive dual immunocytochemistry assay results more
      frequently (p < 0.001), and these positive results were also significantly
      associated with biopsy findings (p < 0.001) and with high-risk genotype HPV
      infection (p = 0.007). Specificity and PPV for the dual assay were 0.972 (0.855
      0.999) and 0.800 (0.284-0.995), respectively, and 1.000 (0.590-1.000) and 1.000
      (0.631-1.000) for HPV detection. CONCLUSIONS: The dual immunocytochemistry assay
      had high specificity and PPV. It reveals a persistent HPV infection, avoiding the
      need for new tissue collections for biopsies or hybrid capture.

PMID- 29566393
TI  - The Influence of Cognitive Bias on Caries Lesion Detection in Preschool Children.
AB  - We aimed to evaluate whether children's caries experience exerts an influence on
      the performance of visual and radiographic methods in detecting nonevident
      proximal caries lesions in primary molars. Eighty children (3-6 years old) were
      selected and classified as having a lower (<=3 decayed, missing, or filled
      surfaces; dmf-s) or higher (> 3 dmf-s) caries experience. Two calibrated
      examiners then assessed 526 proximal surfaces for caries lesions using visual and
      radiographic methods. As a reference standard, 2 other examiners checked the
      surfaces after temporary separation. Noncavitated and cavitated lesion thresholds
      were considered and Poisson multilevel regression analyses were conducted to
      evaluate the influence of caries experience on the performance of diagnostic
      strategies. Accuracy parameters stratified by caries experience were also
      derived. A statistically significant influence of caries experience was observed
      only for visual inspection, with more false-positive results in children with a
      higher caries experience at the noncavitated lesion threshold, and more false
      results at the cavitated threshold. The detection of noncavitated caries lesions
      in children with a higher caries experience was overestimated (specificity =
      0.696), compared to children with a lower caries experience (specificity =
      0.918), probably due to confirmation bias. However, the examiners underestimated
      the detection of cavitated lesions in children with a higher caries experience
      (sensitivity = 0.143) compared to lower-caries-experience children (sensitivity =
      0.222), possibly because of representativeness bias. The radiographic method was
      not influenced by children's caries experience. In conclusion, children's caries
      experience influences the performance of visual inspection in detecting proximal
      caries lesions in primary teeth, evidencing the occurrence of cognitive biases.

PMID- 29566394
TI  - A Randomized Controlled Trial in Routine Clinical Practice Comparing Acceptance
      and Commitment Therapy with Cognitive Behavioral Therapy for the Treatment of
      Major Depressive Disorder.
AB  - BACKGROUND: Since current therapies for depression are effective but not for all
      patients alike, we need to further improve available treatments. Existing
      research suggests that acceptance and commitment therapy (ACT) may effectively
      treat major depressive disorder (MDD). We compared ACT with cognitive behavioral
      therapy (CBT) for depression, testing the hypothesis that CBT would outperform
      ACT. METHODS: We conducted a randomized controlled trial with 82 patients
      suffering from MDD. Data were collected before and after treatment and at the 6
      month follow-up, assessing diagnosis, symptom levels of depression, and quality
      of life. RESULTS: After treatment, the rates of remission from depression were 75
      and 80% for the ACT and CBT conditions, respectively. Patients in both conditions
      further reported significant and large reductions in depressive symptoms and
      improvement in quality of life from before to after treatment as well as at the
      follow-up. Our findings indicated no significant differences between the two
      intervention groups. CONCLUSION: Our results indicate that CBT is not more
      effective in treating depression than ACT. Further research is needed to
      investigate whether ACT and CBT work differently for different groups of patients
      with depression.

PMID- 29566395
TI  - Angiographic and Tomographic Prognostic Factors of Chronic Central Serous
      Chorioretinopathy Treated with Half-Dose Photodynamic Therapy.
AB  - AIMS: To identify the angiographic and tomographic prognostic factors of chronic
      central serous chorioretinopathy (CSC) treated with half-dose photodynamic
      therapy (PDT). METHODS: This is a consecutive series of 61 eyes with chronic CSC
      treated with half-dose PDT from January 1, 2009 to October 31, 2016. RESULTS: The
      mean logMAR best-corrected visual acuity (BCVA) improved from 0.47 to 0.31 at 3
      months (p < 0.001). From multivariate regression, the final BCVA was
      significantly associated with the baseline BCVA (p = 0.003), a diffuse
      hyperfluorescence pattern on indocyanine green angiography (ICGA) (p = 0.024),
      posttreatment shallow irregular pigment epithelium detachment (PED) (p = 0.022),
      and disruption of the ellipsoid zone (p = 0.007). A diffuse hyperfluorescence
      pattern on ICGA was associated with a 77.4 times risk of subretinal fluid
      persistence after treatment (p = 0.009). CONCLUSION: A poor baseline BCVA,
      diffuse hyperfluorescence ICGA pattern, shallow irregular PED, and disruption of
      the ellipsoid zone indicate poor prognosis.

PMID- 29566397
TI  - Per-rectal endoscopic myotomy (PREM) for pediatric Hirschsprung's disease.

PMID- 29566396
TI  - Leading causes of cardiovascular hospitalization in 8.45 million US veterans.
AB  - BACKGROUND: We sought to determine the leading causes of cardiovascular (CV)
      hospitalization, and to describe and compare national rates of CV hospitalization
      by age, gender, race, ethnicity, region, and year, among U.S. veterans. METHODS:
      We evaluated the electronic health records of all veterans aged >=18 years who
      had accessed any healthcare services at either a VA healthcare facility or a non
      VA healthcare facility that was reimbursed by the VA, between January 1 2010 and
      December 31 2014. Among these 8,452,912 patients, we identified the 5 leading
      causes of CV hospitalization and compared rates of hospitalization by age,
      gender, race, ethnicity, region, year and type of VA healthcare user. RESULTS:
      The top 5 causes of CV hospitalization were: coronary atherosclerosis, heart
      failure, acute myocardial infarction, stroke and atrial fibrillation. Overall,
      297,373 (3.5%) veterans were hospitalized for one or more of these cardiovascular
      conditions. The percentage of veterans hospitalized for one or more of these CV
      conditions decreased over time, from 1.23% in 2010 to 1.18% in 2013, followed by
      a slight increase to 1.20% in 2014. There was significant variation in rates of
      CV hospitalization by gender, race, ethnicity, geographic region, and urban vs.
      rural zip code. In particular, older, male, Black, non-Hispanic, urban and
      Continental region veterans experienced the highest rates of CV hospitalizations.
      CONCLUSIONS: Among 8.5 million patients enrolled in the VA healthcare system from
      2010 to 2014, there was substantial variation in rates of CV hospitalization by
      age, gender, race, geographical distribution, year, and use of non-VA (vs. VA
      only) healthcare care facilities.

PMID- 29566398
TI  - Re-intervention for stent-stone complex using intraductal cholangioscopy with
      electrohydraulic lithotripsy after multiple biliary metal stenting.

PMID- 29566399
TI  - Endocuff-assisted underwater snare polypectomy in complex ascending colon
      neoplasia.

PMID- 29566400
TI  - Endoscopic sleeve gastroplasty of the remnant stomach in Roux-en-Y gastric
      bypass: a novel approach to a gastrogastric fistula with weight regain.

PMID- 29566401
TI  - Endoscopic treatment of esophageal intramural abscess caused by embedded metal
      clip: a rare delayed complication of endoscopic submucosal dissection.

PMID- 29566403
TI  - A Theoretical Approach to Selection of a Biologically Active Substance in Ultra
      Low Doses for Effective Action on a Biological System.
AB  - BACKGROUND AND AIM: An approach is offered to selecting a biologically active
      substance (BAS) in ultra-low dose for effective action on a biological system
      (BS). The technique is based on the assumption that BAS in ultra-low doses exerts
      action on BS by means of spin supercurrent emerging between the spin structure
      created by BAS, on the one hand, and the spin structure created by BS, on the
      other hand. According to modern quantum-mechanical concepts, these spin
      structures may be virtual particles pairs having precessing spin (that is, be
      essentially spin vortices in the physical vacuum) and created by the quantum
      entities that BAS and BS consist of. The action is effective provided there is
      equality of precession frequencies of spins in these spin structures. METHOD: In
      this work, some methods are considered for determining the precession frequencies
      of spins in virtual particles pairs: (1) determination of energy levels of
      quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of
      the virtual particles pair spin, the effect being initiated by action of magnetic
      vector potential (the spin-flip effect takes place when the varied frequency of
      the magnetic vector potential equals the precession frequency of the spin); (3)
      determining the frequencies of photons effectively acting on BS. RESULTS AND
      CONCLUSION: It is shown that the effect of BAS in ultra-low doses on BS can be
      replaced by the effect of a beam of low-intensity photons, if the frequency of
      photons equals the precession frequency of spin in spin structures created by BS.
      Consequently, the color of bodies placed near a biological system is able to
      exert an effective action on the biological system: that is "color therapy" is
      possible. It is also supposed that the spin-flip effect may be used not only for
      determining the precession frequency of spin in spin structures created by BS but
      also for therapeutic action on biological systems.

PMID- 29566402
TI  - Significance of BRAF V600E Mutation and Cytomorphological Features for the
      Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically
      Indeterminate Thyroid Nodules.
AB  - BACKGROUND: Ultrasound guided fine needle aspiration biopsy with cytologic
      analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up
      to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim
      of this study was to estimate the diagnostic value of BRAF V600E mutation status
      combined with cytomorphological features for diagnosis of papillary thyroid
      cancer (PTC) in cytologically indeterminate thyroid nodules. METHODS: A
      prospective study analyzed patients who had ultrasound suspicious thyroid
      nodules, underwent fine needle aspiration and cytological examination, and were
      classified according to the Bethesda system. Patients from indeterminate
      diagnostic categories were examined for BRAF V600E mutation and 22
      cytomorphological features, and underwent thyroid surgery. A binary logistic
      regression model was used to evaluate the diagnostic utility. RESULTS: A total of
      219 patients met study criteria. After histological examination, 77 (35.2%)
      patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid
      disease. According to logistic regression model, significant features for PTC
      diagnosis were: liquid colloid consistency, papillary structures, eosinophilic
      colloid bodies, and BRAF V600E mutation. Risk groups classified by this model
      have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI:
      96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative
      predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI:
      88.4 to 95.8) for PTC diagnosis. CONCLUSIONS: Evaluation of BRAF V600E mutation
      status combined with cytomorphological features for diagnosis of PTC in
      cytologically indeterminate thyroid nodules can significantly improve diagnostic
      accuracy and reduce the number of diagnostic operations (calculator available at
      www.ptc-calc.we2host.lt).

PMID- 29566404
TI  - In Vitro Effects of Homeopathic Drugs on Cultured Escherichia coli.
AB  - BACKGROUND: Recurrent urinary tract infections (UTIs) are one of the most common
      morbidities in persons with neurogenic lower urinary tract dysfunction (NLUTD).
      Repetitive antibiotic treatment increases the risk of selecting multi-resistant
      bacteria. Homeopathic treatment has been reported to be effective in these
      patients. The mechanism of action, however, has not been clarified. Recently, a
      direct bactericidal effect of homeopathic remedies was shown. Such an effect is
      not in accordance with the general principles of homeopathy. To test this
      paradigm, we assessed the in vitro effects of homeopathic drugs on Escherichia
      coli derived from patients with NLUTD. METHODS: E. coli bacteria were harvested
      from 28 consecutive urine cultures. Standard antibiotic resistance testing and
      simultaneous resistance testing to homeopathic drugs (Apis mellifica, Cantharis,
      Causticum hahnemanni, Staphysagria, Nux vomica, Berberis vulgaris, and
      Lycopodiumclavatum) in high (C30) potency were performed. RESULTS: No significant
      inhibitory effect of any of the tested homeopathic drugs on any E. coli
      population could be found, irrespective of their sensitivity to antibiotic
      treatment. CONCLUSION: Based on our results, effects of homeopathic treatment of
      UTI are not based on direct bactericidal or bacteriostatic effects. These
      findings are in concordance with the hypothesis that homeopathy is based on host
      effects: for example, activation of the immune system, rather than effects on
      pathogens.

PMID- 29566405
TI  - Correction: Androgen Receptor CAG Repeat Length in Relation to Phenotype Among
      Females with Nonclassical 21-Hydroxylase Deficiency.

PMID- 29566406
TI  - Off-Pump Coronary Artery Bypass Grafting and Stroke-Exploratory Analysis of the
      GOPCABE Trial and Methodological Considerations.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass
      (off-pump CABG) may reduce severe adverse events including stroke. METHODS: In
      the German Off-Pump Coronary Artery Bypass Grafting in Elderly patients trial,
      the rate of major adverse cardiovascular events was compared in 2,394 elderly (>=
      75 years) patients undergoing CABG with (on-pump) or without (off-pump)
      cardiopulmonary bypass. This exploratory post-hoc analysis investigated the
      impact of surgical aortic manipulation on the rate of stroke. RESULTS: There was
      no significant difference in the rate of stroke within 30 days after surgery
      between both groups (off-pump: 2.2%; on-pump: 2.7%; odds ratio [OR]: 0.83 [0.5
      1.38]; p = 0.47). Within the off-pump group, different degrees of aortic
      manipulation did not lead to significant different stroke rates (tangential
      clamping: 2.3%; OR 0.86 [0.46-1.60]; clampless device: 1.8%; OR 0.67 [0.26-1.75];
      no aortic manipulation: 2.4%; OR 0.88 [0.37-2.14]). An aggregate analysis
      including more than 10,000 patients out of the four recent major trials also
      yielded comparable stroke rates for on- and off-pump CABG (off-pump: 1.4%; on
      pump: 1.7%; OR 0.87 [0.64-1.20]). CONCLUSION: Within recent prospective
      randomized multicenter trials off-pump CABG did not result in lower stroke rates.
      The possible intrinsic benefit of off-pump CABG may be offset by the complexity
      of the operative therapy as well as the multiple pathomechanisms involved in
      perioperative stroke.

PMID- 29566407
TI  - Intracranial Hemorrhage and Early Mortality in Patients Receiving Extracorporeal
      Membrane Oxygenation for Severe Respiratory Failure.
AB  - Intracranial hemorrhage (ICH) is a serious complication in patients receiving
      veno-venous extracorporeal membrane oxygenation (VV-ECMO) and is associated with
      high mortality. It is unknown whether ICH may be a consequence of the ECMO or of
      an underlying disease. The authors first aimed to assess the incidence of ICH at
      initiation and during the course of VV-ECMO and its associated mortality. The
      second aim was to identify clinical and laboratory measures that could predict
      the development of ICH in severe respiratory failure. Data were collected from a
      total number of 165 patients receiving VV-ECMO from January, 2012 to December,
      2016 in a single tertiary center and treated according to a single protocol. Only
      patients who had a brain computed tomography within 24 hours of initiation of
      ECMO (n = 149) were included for analysis. The prevalence and incidence of ICH at
      initiation and during the course of VV-ECMO (at median 9 days) were 10.7%
      (16/149) and 5.2% (7/133), respectively. Thrombocytopenia and reduced creatinine
      clearance (CrCL) were independently associated with increased risk of ICH on
      admission; odds ratio (95% confidence interval): 22.6 (2.6-99.5), and 10.8 (5.6
      16.2). Only 30-day (not 180-day) mortality was significantly higher in patients
      with ICH on admission versus those without (37.5% [6/16] vs 16.4% [22/133]; p =
      0.03 and 43.7% [7/16] vs 26.3% [35/133]; p = 0.15, respectively). Reduced CrCL
      and thrombocytopenia were associated with ICH at initiation of VV-ECMO. The
      higher incidence of ICH at initiation suggests it is more closely related to the
      severity of the underlying lung injury than to the VV-ECMO itself. ICH at VV-ECMO
      initiation was associated with early mortality.

PMID- 29566408
TI  - Surgical Complications after Right Hepatectomy for Live Liver Donation: Largest
      Single-Center Western World Experience.
AB  - The authors assessed the incidence, management, and risk factors for
      postoperative complications after right lobe (RL) live donor hepatectomy in a
      high-volume center in North America. All donors undergoing an RL live donor
      hepatectomy between 2000 and 2017 at our institution were included. The primary
      outcome was the development of complications (both medical and surgical).
      Predictors of postoperative complications were determined by logistic regression.
      A total of 587 patients underwent RL live donor hepatectomy. Among those, 187
      postoperative complications were diagnosed in 141 (24%) patients. One patient had
      >90-day morbidity, and there were no donor deaths. Overall complications were
      significantly higher in the first era, 2000 to 2008 (81 [57.4%]) versus the
      second era, 2009 to 2017 (60 [42.6%]) (p = 0.01). On multivariate analysis, the
      only predictor of postoperative complications was the center volume of RL live
      donor hepatectomy in the previous 12 months with an odds ratio of 0.97 (95%
      confidence interval: 0.95-0.99). In conclusion, increasing center volume is
      associated with lower rates of postoperative complications after RL living liver
      donation.

PMID- 29566409
TI  - Botryane Sesquiterpenoids, Cyclopentadepsipeptides, Xanthones, and Trichothecenes
      from Trichoderma oligosporum.
AB  - Five new botryane sesquiterpenes (1: -5: ), one new cyclopentadepsipeptide (9: ),
      and two new xanthones (11:  - 12: ), together with 11 known compounds, were
      isolated from Trichoderma oligosporum. The structures of the new compounds were
      identified by comprehensive spectroscopic methods including nuclear magnetic
      resonance and mass spectrometry. The cytotoxicity of 1: -19: was evaluated
      against K562, A549, and ASPC cell lines. Compounds 5, 8, 11, 17: , and 18: showed
      cytotoxicity against the K562 cell line with more than 50% inhibition at 12.5 uM.
      As to A549 cell line, compound 8: showed the strongest cytotoxicity with
      approximately 50% inhibition at 25.0 uM. No compounds showed cytotoxicity against
      the ASPC cell line.

PMID- 29566410
TI  - Mechanical Allodynia Predicts Better Outcome of Surgical Decompression for
      Painful Diabetic Peripheral Neuropathy.
AB  - BACKGROUND:  To determine the role of mechanical allodynia (MA) in predicting
      good surgical outcome for painful diabetic peripheral neuropathy (DPN). MATERIALS
      AND METHODS:  Data of 192 patients with painful DPN were collected in this study,
      with 148 surgical patients and 44 patients in the control group. Both groups were
      further divided into subgroups based on the presence of MA on admission. Clinical
      evaluations including the visual analog scale (VAS), the Hospital Anxiety and
      Depression Scale (HADS), nerve conduction velocity (NCV), and high-resolution
      ultrasonography (cross-sectional area, CSA) were performed preoperatively and
      postoperatively. RESULTS:  The levels of VAS and HADS and the results of NCV and
      CSA were improved in the surgical group (p < 0.05). In the surgical subgroups,
      pain reduction, psychiatric amelioration, improvement in NCVs, and the
      restoration of the CSA were observed in patients with signs of MA (p < 0.05),
      whereas only pain reduction, psychiatric amelioration, and restoration of the CSA
      were noted in patients without signs of MA (p > 0.05). Furthermore, better pain
      reduction was achieved in patients with MA when compared with those without MA (p
      < 0.05). CONCLUSIONS:  MA is proved to be a reliable predictor of good surgical
      outcome for painful DPN.

PMID- 29566411
TI  - Surgery of Neonates: What's New in Dealing with Perioperative Complications?

PMID- 29566412
TI  - The Evolution of Antithrombotic Care in Cardiovascular Patients.

PMID- 29566413
TI  - Rivaroxaban: A New Treatment Paradigm in the Setting of Vascular Protection?
AB  - The pathophysiology of atherosclerosis involves a diseased endothelium, lipid
      accumulation and low-grade inflammation. In later stages of coronary artery
      disease (CAD) and peripheral arterial disease (PAD), plaque rupture may induce
      atherothrombosis caused by fibrin formation and platelet activation, leading to
      vessel occlusion with subsequent organ damage such as myocardial infarction,
      stroke or limb ischaemia. Because of the high disease burden associated with CAD
      and PAD, there is a need for continuous vascular protection beyond currently
      available treatments including antiplatelet agents. Due to its central role in
      the coagulation cascade, inhibition of factor Xa, with the subsequent reduced
      thrombin formation that impacts not only fibrin but also platelets, may provide
      additional benefit over using antiplatelets alone. Evidence from Anti-Xa Therapy
      to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with
      Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51 (ATLAS-ACS 2
      TIMI 51) supports the use of the direct, oral, factor Xa inhibitor rivaroxaban
      (2.5 mg twice-daily [bid] and 5 mg bid) in reducing mortality and morbidity in
      patients with acute coronary syndrome, when combined with antiplatelets. Here, we
      review the role of rivaroxaban in three clinical trials of CAD and/or PAD:
      Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS),
      Vascular Outcomes studY of ASA alonG with rivaroxaban in Endovascular or surgical
      limb Revascularization for PAD (VOYAGER PAD) and Cardiovascular Outcome
      Modification, Measurement AND Evaluation of Rivaroxaban in patients with Heart
      Failure (COMMANDER HF).

PMID- 29566414
TI  - Understanding the Value of Real-World Evidence: Focus on Stroke Prevention in
      Atrial Fibrillation with Rivaroxaban.
AB  - Real-world data are a well-recognized component within the drug lifecycle, and
      such data are generated from a range of sources and study designs, including
      claims databases, electronic health records, non-interventional studies (NIS) and
      registries. While this information can be of vital clinical importance, there may
      be challenges in understanding the relevance of the differing study designs,
      endpoints and populations. Here, we summarize the value of real-world evidence
      and considerations pertinent to their use in clinical research. Owing to the
      variety of analyses being conducted using real-world data, it is important for
      researchers and clinicians to have a clear understanding of the nature and origin
      of those data, and to ensure they are valid, reliable and robust in terms of
      extrapolating meaningful findings. There are crucial questions to address when
      evaluating real-world studies, and we introduce a checklist to meet these
      objectives. In addition to advice for appraising data quality and study designs,
      several updates will be covered from real-world studies of rivaroxaban for stroke
      prevention in patients with atrial fibrillation (AF): the nationwide Danish
      cohort study, U.S. Department of Defense Military Health System database,
      retrospective claim database study REAFFIRM and a pooled analysis from the global
      NIS XArelto on preveNtion of sTroke and non-central nervoUS system systemic
      embolism in patients with non-valvular atrial fibrillation (XANTUS). Real-world
      studies consistently show that rivaroxaban is an effective treatment option with
      acceptable safety when used for stroke prevention in a large number of patients
      with AF across the globe.

PMID- 29566415
TI  - The Rivaroxaban Program and the Management of Unmet Needs in Thromboembolic
      Disease.
AB  - Rivaroxaban is a non-vitamin K antagonist oral anticoagulant that acts as a
      direct factor Xa inhibitor, and is widely used for the prevention and treatment
      of thromboembolic disorders. As further knowledge gaps are identified in
      thrombosis management, the rivaroxaban research program has expanded in an
      attempt to elucidate the wider benefits of rivaroxaban. An increased
      understanding of the interactions taking place within the coagulation cascade may
      support a broader role for rivaroxaban (2.5 mg twice daily [bid] or 5 mg bid) in
      the setting of vascular protection, either alone or in combination with an
      antiplatelet agent. The aim of this article is to describe the potential role of
      rivaroxaban in the context of vascular protection and provide an overview of
      recently completed and ongoing randomized controlled trials of rivaroxaban in the
      areas of stroke prevention, venous protection and vascular protection.

PMID- 29566416
TI  - Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs
      with Rivaroxaban.
AB  - With improved life expectancy and the aging population, the global burden of
      atrial fibrillation (AF) continues to increase, and with AF comes an estimated
      fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy
      is more effective in reducing the risk of ischaemic stroke in AF patients than
      acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel.
      Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke
      prevention in patients with non-valvular AF. The optimal anticoagulant strategy
      to prevent thromboembolism in AF patients who are undergoing percutaneous
      coronary intervention and stenting, those who have undergone successful
      transcatheter aortic valve replacement and those with embolic stroke of
      undetermined source are areas of ongoing research. This article provides an
      update on three randomized controlled trials of rivaroxaban, a direct, oral
      factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of
      stroke prevention: oPen-label, randomized, controlled, multicentre study
      explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral
      vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who
      undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New
      Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to
      prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial
      and the Global study comparing a rivAroxaban-based antithrombotic strategy to an
      antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to
      Optimize clinical outcomes (GALILEO) trial. The data from these studies are
      anticipated to help address continuing challenges for a range of patients at risk
      of stroke.

PMID- 29566417
TI  - Treatment Challenges in Venous Thromboembolism: An Appraisal of Rivaroxaban
      Studies.
AB  - Venous thromboembolism (VTE) presents a continuing clinical burden to healthcare
      systems and there are patient groups for whom VTE management is challenging.
      Depending on the patient profile, the optimal duration of anticoagulation for VTE
      treatment can be unclear. EINSTEIN CHOICE was a Phase III, randomized, double
      blind trial that compared the safety and efficacy of two once-daily (od) doses of
      the direct, oral factor Xa inhibitor rivaroxaban (20 and 10 mg) with
      acetylsalicylic acid (ASA; 100 mg daily) for prevention of recurrent VTE.
      Extended therapy with rivaroxaban at either dose was more effective than ASA at
      preventing recurrent VTE without increasing bleeding risk. Another group that is
      challenging to treat in the context of VTE is patients with cancer-associated
      thrombosis. Cancer is associated with a hypercoagulable state, while cancer
      treatment itself may increase VTE risk. Evidence supporting the use of non
      vitamin K antagonist oral anticoagulants in patients with cancer is growing
      through specifically designed studies. Cancer Associated thrombosis-expLoring
      soLutions for patIentS through Treatment and prevention with rivarOxaban
      (CALLISTO) is an international research program exploring the role of rivaroxaban
      for the prevention and treatment of cancer-associated thrombosis. Here, we
      present overviews of three CALLISTO studies: PRO-LAPS II, CASTA-DIVA and COSIMO.
      Currently available and anticipated results from studies in a variety of patients
      at risk of or with VTE will provide valuable insights and seek to optimize future
      VTE management.

PMID- 29566418
TI  - Estradiol: A Steroid with Multiple Facets.
AB  - Seventy-five glorious years have passed since estradiol was discovered by Edward
      Doisy. From discovery in the ovaries to delineation of diverse physiological
      effects, research on estrogens has covered a lot of ground. Estrogen receptors
      that mediate estrogenic effects, have been detected not only in reproductive
      organs, but also in other body organs. Estrogen receptors function either as
      conventional transcription factors or as rapid signal transducers. These
      different modes of action are opted by estrogens to elicit an array of
      reproductive and non-reproductive functions. It is well established that
      estrogens promote cell proliferation in various tissues and hence are also linked
      to carcinogenesis. Anti-estrogens are being used as adjunct therapies for cancers
      since several years. On the other hand, estrogen-based strategies are used to
      alleviate adverse effects of menopause. Apart from estrogens synthesized in
      various organs, exposure to environmental estrogens can also impact physiology.
      Thus, too much or too less of estrogens can tip the balance and lead to
      unfavorable consequences. Multiple estrogen receptors with their tissue- or cell
      type-specific expression eliciting dose-dependent effects make it perplexing to
      'unify' estrogenic actions in diverse tissues/organs. This warrants more research
      on estrogen-mediated effects and their regulation in somatic and reproductive
      tissues. This review presents physiological and pathological aspects of estrogens
      thus highlighting the good, bad, and ugly facets of estrogens.

PMID- 29566419
TI  - EFSUMB Recommendations and Clinical Guidelines for Intestinal Ultrasound (GIUS)
      in Inflammatory Bowel Diseases.
AB  - The accuracy and usefulness of gastrointestinal ultrasound (GIUS) for detecting
      activity and complications of inflammatory bowel diseases (IBD), has been
      reported in studies, promoting this technique as an important tool for the
      management of IBD patients. Whilst well recognised by international guidelines,
      standardization and general agreement in the definition of the luminal and extra
      intestinal features, still need to be well defined.A task force group of 17
      experts in GIUS faced this issue, by developing recommendations and clinical
      guidelines for the use of GIUS in IBD, under the auspices of EFSUMB. This article
      presents the consensus on the current data on sonographic features of IBD and
      summarises the accuracy of different sonographic modalities for the management of
      IBD patients.

PMID- 29566420
TI  - Evaluation of Inter-System Variability in Liver Stiffness Measurements.
AB  - AIM:  The primary aim of this study was to determine the inter-system variability
      of liver stiffness measurements (LSMs) in patients with varying degrees of liver
      stiffness. The secondary aim was to determine the inter-observer variability of
      measurements. MATERIALS AND METHODS:  21 individuals affected by chronic
      hepatitis C and 5 healthy individuals were prospectively enrolled. The assessment
      of LSMs was performed using six ultrasound (US) systems, four of which with point
      shear wave elastography (p-SWE) and two with 2 D shear wave elastography (2D-SWE)
      systems. The Fibroscan (Echosens, France) was used as the reference standard.
      Four observers performed the measurements in pairs (A-B, C-D). The agreement
      between different observers or methods was calculated using Lin's concordance
      correlation coefficient. The Bland-Altman limits of agreement (LOA) were
      calculated as well. RESULTS:  There was agreement above 0.80 for all pairs of
      systems. The mean difference between the values of the systems with 2D-SWE
      technique was 1.54 kPa, whereas the maximum mean difference between the values of
      three out of four systems with the pSWE technique was 0.79 kPa. The intra-patient
      concordance for all systems was 0.89 (95 % CI: 0.83 - 0.94). Inter-observer
      agreement was 0.96 (95 % CI: 0.94 - 0.98) for the pair of observers A-B and 0.93
      (95 % CI: 0.89 - 0.96) for the pair of observers C-D. CONCLUSION:  The results of
      this study show that the agreement between LSMs performed with different US
      systems is good to excellent and the overall inter-observer agreement in "ideal
      conditions" is above 0.90 in expert hands.

PMID- 29566421
TI  - The Role of Virtual Rehabilitation in Total Knee and Hip Arthroplasty.
AB  - Virtual rehabilitation therapies have been developed to focus on improving care
      for those suffering from various musculoskeletal disorders. There has been
      evidence suggesting that real-time virtual rehabilitation may be equivalent to
      conventional methods for adherence, improvement of function, and relief of pain
      seen in these conditions. This study specifically evaluated the use of a virtual
      physical therapy/rehabilitation platform for use during the postoperative period
      after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The use of
      this technology has the potential benefits that allow for patient adherence, cost
      reductions, and coordination of care.

PMID- 29566422
TI  - Clinical Prospective Study on the Use of Subcutaneous Carboxytherapy in the
      Treatment of Diabetic Foot Ulcer.
AB  - Diabetic footfoot ulcer (DFU) is a serious complication of diabetes mellitus, and
      possibly the major morbidity of the diabetic foot. It is the most common foot
      injury in diabetic patients and can lead to lower-extremity amputation.
      Management of DFU requires a systematic knowledge of the major risk factors for
      amputation, frequent routine evaluation, scrupulous preventive maintenance, and
      correction of peripheral arterial insufficiency. Carboxytherapy refers to the
      subcutaneous injection of CO2 to improve the microcirculation and promote wound
      healing by stimulating the microcirculation. Since optimal ulcer-healing requires
      adequate tissue perfusion, it is considered that carboxytherapy could be useful
      in the treatment of DFU. The present prospective clinical study included 40
      patients with different sizes and types of chronic DFU. In addition to cleaning
      of the wound, antibiotics and debridement as necessary, the treatment protocol
      included blood sugar control, medication, healthy habits, no weight-bearing, and
      carboxytherapy. The results showed that this treatment that included
      carboxytherapy promoted wound-healing and prevented amputation. These positive
      effects should be confirmed through a complete study that includes different
      clinical and instrumental parameters.

PMID- 29566423
TI  - A Prospective Clinical and Instrumental Study on the Effects of a Transcutaneous
      Cosmeceutical Gel that is Claimed to Produce CO2.
AB  - Carboxytherapy is the therapeutic use of carbon dioxide (CO2) in its gaseous
      state. Since 1933, carboxytherapy has referred to either the subcutaneous
      injection of CO2 or percutaneous application in a warm bath. The present clinical
      study was performed to determine if there were any changes in the dermis after
      the application of a transcutaneous gel, which is claimed to produce CO2, and, if
      so, how these changes compared to those with CO2 injection. Ten patients received
      transcutaneous treatment with the gel on one side of the face and the other side
      without any product was used as a control. We used videocapillaroscopy with an
      optic probe (VCSO) to evaluate the changes in the microcirculation of the skin.
      VCSO was performed for the treated right and untreated left ear lobes in each
      patient. VCSO was performed before treatment was started (VCSO1) and after 7 days
      of treatment (VCSO2). A comparison of VCSO1 to VCSO2 showed an increase in the
      microcirculation, an increase in vertical and horizontal capillaries, and a
      reduction in the area of ischemia. These results are similar to those observed in
      other studies with CO2 injection. In conclusion, use of this transcutaneous CO2
      gel produced changes in the dermis similar to those observed with subcutaneous
      injection of CO2.

PMID- 29566424
TI  - Integration of the nasal complex: Implications for developmental and evolutionary
      change in modern humans.
AB  - OBJECTIVES: Assessing the strength of integration among different regions of the
      modern human nasal complex is important for developing a more thorough
      understanding of the determinants of nasal morphology. Given the morphogenetic
      influence of cartilage on adjacent intramembranous growth sites, the interaction
      between chondrocranial- versus intramembranous-derived nasal structures may have
      a significant influence on patterns of nasal variation. The purpose of this study
      is to examine integration between the chondrocranial- and intramembranous-derived
      regions of the nasal complex. MATERIALS AND METHODS: Using computed tomograph
      (CT) scans, we collected three-dimensional coordinate landmark data from a static
      adult sample (n = 62). First, using centroid size, and the symmetric and
      asymmetric components of shape variation, we examined the strength of integration
      between landmarks representing chondrocranial-derived structures (e.g., ethmoid,
      external nasal cartilages) and landmarks representing intramembranous-derived
      structures (nasal floor, anterior nasal aperture, etc.). Second, given that the
      strength of integration is a relative measure, we compared integration between
      chondrocranial- and intramembranous-derived structures to the more modularized
      external and internal regions of the nasal complex. RESULTS: There was
      significant moderate morphological integration between chondrocranial- versus
      intramembranous-derived regions of the nasal complex. Moreover, integration
      between chondrocranial- versus intramembranous-derived structures was
      consistently stronger when compared to external versus internal regions for both
      the symmetric and asymmetric components of variation. Thus, more covariation
      within the nasal complex could be explained by the relationship between
      chondrocranial- and intramembranous-derived structures. CONCLUSIONS: Our results
      suggest that the interaction between chondrocranial- and intramembranous-derived
      structures may be an important determinant in the patterning of nasal complex
      variation.

PMID- 29566425
TI  - Cognitive-behavioural interventions for attention deficit hyperactivity disorder
      (ADHD) in adults.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a developmental
      condition characterised by symptoms of inattention, hyperactivity and
      impulsivity, along with deficits in executive function, emotional regulation and
      motivation. The persistence of ADHD in adulthood is a serious clinical
      problem.ADHD significantly affects social interactions, study and employment
      performance.Previous studies suggest that cognitive-behavioural therapy (CBT)
      could be effective in treating adults with ADHD, especially when combined with
      pharmacological treatment. CBT aims to change the thoughts and behaviours that
      reinforce harmful effects of the disorder by teaching people techniques to
      control the core symptoms. CBT also aims to help people cope with emotions, such
      as anxiety and depression, and to improve self-esteem. OBJECTIVES: To assess the
      effects of cognitive-behavioural-based therapy for ADHD in adults. SEARCH
      METHODS: In June 2017, we searched CENTRAL, MEDLINE, Embase, seven other
      databases and three trials registries. We also checked reference lists,
      handsearched congress abstracts, and contacted experts and researchers in the
      field. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating any
      form of CBT for adults with ADHD, either as a monotherapy or in conjunction with
      another treatment, versus one of the following: unspecific control conditions
      (comprising supportive psychotherapies, no treatment or waiting list) or other
      specific interventions. DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedures suggested by Cochrane. MAIN RESULTS: We included 14
      RCTs (700 participants), 13 of which were conducted in the northern hemisphere
      and 1 in Australia.Primary outcomes: ADHD symptomsCBT versus unspecific control
      conditions (supportive psychotherapies, waiting list or no treatment)- CBT versus
      supportive psychotherapies: CBT was more effective than supportive therapy for
      improving clinician-reported ADHD symptoms (1 study, 81 participants; low-quality
      evidence) but not for self-reported ADHD symptoms (SMD -0.16, 95% CI -0.52 to
      0.19; 2 studies, 122 participants; low-quality evidence; small effect size).- CBT
      versus waiting list: CBT led to a larger benefit in clinician-reported ADHD
      symptoms (SMD -1.22, 95% CI -2.03 to -0.41; 2 studies, 126 participants; very low
      quality evidence; large effect size). We also found significant differences in
      favour of CBT for self-reported ADHD symptoms (SMD -0.84, 95% CI -1.18 to -0.50;
      5 studies, 251 participants; moderate-quality evidence; large effect size).CBT
      plus pharmacotherapy versus pharmacotherapy alone: CBT with pharmacotherapy was
      more effective than pharmacotherapy alone for clinician-reported core symptoms
      (SMD -0.80, 95% CI -1.31 to -0.30; 2 studies, 65 participants; very low-quality
      evidence; large effect size), self-reported core symptoms (MD -7.42 points, 95%
      CI -11.63 points to -3.22 points; 2 studies, 66 participants low-quality
      evidence) and self-reported inattention (1 study, 35 participants).CBT versus
      other interventions that included therapeutic ingredients specifically targeted
      to ADHD: we found a significant difference in favour of CBT for clinician
      reported ADHD symptoms (SMD -0.58, 95% CI -0.98 to -0.17; 2 studies, 97
      participants; low-quality evidence; moderate effect size) and for self-reported
      ADHD symptom severity (SMD -0.44, 95% CI -0.88 to -0.01; 4 studies, 156
      participants; low-quality evidence; small effect size).Secondary outcomesCBT
      versus unspecific control conditions: we found differences in favour of CBT
      compared with waiting-list control for self-reported depression (SMD -0.36, 95%
      CI -0.60 to -0.11; 5 studies, 258 participants; small effect size) and for self
      reported anxiety (SMD -0.45, 95% CI -0.71 to -0.19; 4 studies, 239 participants;
      small effect size). We also observed differences in favour of CBT for self
      reported state anger (1 study, 43 participants) and self-reported self-esteem (1
      study 43 participants) compared to waiting list. We found no differences between
      CBT and supportive therapy (1 study, 81 participants) for self-rated depression,
      clinician-rated anxiety or self-rated self-esteem. Additionally, there were no
      differences between CBT and the waiting list for self-reported trait anger (1
      study, 43 participants) or self-reported quality of life (SMD 0.21, 95% CI -0.29
      to 0.71; 2 studies, 64 participants; small effect size).CBT plus pharmacotherapy
      versus pharmacotherapy alone: we found differences in favour of CBT plus
      pharmacotherapy for the Clinical Global Impression score (MD -0.75 points, 95% CI
      -1.21 points to -0.30 points; 2 studies, 65 participants), self-reported
      depression (MD -6.09 points, 95% CI -9.55 points to -2.63 points; 2 studies, 66
      participants) and self-reported anxiety (SMD -0.58, 95% CI -1.08 to -0.08; 2
      studies, 66 participants; moderate effect size). We also observed differences
      favouring CBT plus pharmacotherapy (1 study, 31 participants) for clinician
      reported depression and clinician-reported anxiety.CBT versus other specific
      interventions: we found no differences for any of the secondary outcomes, such as
      self-reported depression and anxiety, and findings on self-reported quality of
      life varied across different studies. AUTHORS' CONCLUSIONS: There is low-quality
      evidence that cognitive-behavioural-based treatments may be beneficial for
      treating adults with ADHD in the short term. Reductions in core symptoms of ADHD
      were fairly consistent across the different comparisons: in CBT plus
      pharmacotherapy versus pharmacotherapy alone and in CBT versus waiting list.
      There is low-quality evidence that CBT may also improve common secondary
      disturbances in adults with ADHD, such as depression and anxiety. However, the
      paucity of long-term follow-up data, the heterogeneous nature of the measured
      outcomes, and the limited geographical location (northern hemisphere and
      Australia) limit the generalisability of the results. None of the included
      studies reported severe adverse events, but five participants receiving different
      modalities of CBT described some type of adverse event, such as distress and
      anxiety.

PMID- 29566426
TI  - Morphological integration of anatomical, developmental, and functional
      postcranial modules in the crab-eating macaque (Macaca fascicularis).
AB  - OBJECTIVES: Integration and modularity reflect the coordinated action of past
      evolutionary processes and, in turn, constrain or facilitate phenotypic
      evolvability. Here, we analyze magnitudes of integration in the macaque
      postcranium to test whether 20 a priori defined modules are (1) more tightly
      integrated than random sets of postcranial traits, and (2) are differentiated
      based on mode of definition, with developmental modules expected to be more
      integrated than functional or anatomical modules. MATERIALS AND METHODS: The 3D
      morphometric data collected for eight limb and girdle bones for 60 macaques were
      collated into anatomical, developmental, and functional modules. A resampling
      technique was used to create random samples of integration values for each module
      for statistical comparison. RESULTS: Our results found that not all a priori
      defined modules were more strongly integrated than random samples of postcranial
      traits and that specific types of modules did not present consistent patterns of
      integration. Rather, girdle and joint modules were consistently less integrated
      than limb modules, and forelimb elements were less integrated than hindlimbs.
      DISCUSSION: The results suggest that morphometrically complex modules tend to be
      less integrated than simple limb bones, irrespective of the number of available
      traits. However, differences in integration of the fore- and hindlimb more likely
      reflects the multitude of locomotory, feeding, and social functions involved. It
      remains to be tested whether patterns of integration identified here are primate
      universals, and to what extent they vary depending on phylogenetic or functional
      factors.

PMID- 29566427
TI  - Risk of major amputation in patients with intermittent claudication undergoing
      early revascularization.
AB  - BACKGROUND: Revascularization is being used increasingly for the treatment of
      intermittent claudication and yet few studies have reported the long-term
      outcomes of this strategy. The aim of this study was to compare the long-term
      outcome of patients with intermittent claudication who underwent
      revascularization compared with a group initially treated without
      revascularization. METHODS: Patients with symptoms of intermittent claudication
      and a diagnosis of peripheral arterial disease were recruited from outpatient
      clinics at three hospitals in Queensland, Australia. Based on variation in the
      practices of different vascular specialists, patients were either treated by
      early revascularization or received initial conservative treatment. Patients were
      followed in outpatient clinics using linked hospital admission record data. The
      primary outcome was the requirement for major amputation. Kaplan-Meier curves,
      Cox regression and competing risks analyses were used to compare major amputation
      rates. RESULTS: Some 456 patients were recruited; 178 (39.0 per cent) underwent
      early revascularization and 278 (61.0 per cent) had initial conservative
      treatment. Patients were followed for a mean(s.d.) of 5.00(3.37) years. The
      estimated 5-year major amputation rate was 6.2 and 0.7 per cent in patients
      undergoing early revascularization and initial conservative treatment
      respectively (P = 0.003). Early revascularization was associated with an
      increased requirement for major amputation in models adjusted for other risk
      factors (relative risk 5.40 to 4.22 in different models). CONCLUSION: Patients
      presenting with intermittent claudication who underwent early revascularization
      appeared to be at higher risk of amputation than those who had initial
      conservative treatment.

PMID- 29566429
TI  - Use of the Physician Orders for Scope of Treatment Program in Indiana Nursing
      Homes.
AB  - OBJECTIVES: To assess the use of the Indiana Physician Orders for Scope of
      Treatment (POST) form to record nursing home (NH) resident treatment preferences
      and associated practices. DESIGN: Survey. SETTING: Indiana NHs. PARTICIPANTS:
      Staff responsible for advance care planning in 535 NHs. MEASUREMENTS: Survey
      about use of the Indiana POST, related policies, and educational activities.
      METHODS: NHs were contacted by telephone or email. Nonresponders were sent a
      brief postcard survey. RESULTS: Ninety-one percent (n=486) of Indiana NHs
      participated, and 79% had experience with POST. Of the 65% of NHs that complete
      POST with residents, 46% reported that half or more residents had a POST form.
      POST was most often completed at the time of admission (68%). Only 52% of
      participants were aware of an existing facility policy regarding use of POST; 80%
      reported general staff education on POST. In the 172 NHs not using POST, reasons
      for not using it included unfamiliarity with the tool (23%) and lack of facility
      policies (21%). CONCLUSION: Almost 3 years after a grassroots campaign to
      introduce the voluntary Indiana POST program, a majority of NHs were using POST
      to support resident care. Areas for improvement include creating policies on POST
      for all NHs, training staff on POST conversations, and considering processes that
      may enhance the POST conversation, such as finding an optimal time to engage in
      conversations about treatment preferences other than a potentially rushed
      admission process.

PMID- 29566428
TI  - Elder Abuse Identification in the Prehospital Setting: An Examination of State
      Emergency Medical Services Protocols.
AB  - OBJECTIVES: To describe statewide emergency medical service (EMS) protocols
      relating to identification, management, and reporting of elder abuse in the
      prehospital setting. DESIGN: Cross-sectional analysis. SETTING: Statewide EMS
      protocols in the United States. PARTICIPANTS: Publicly available statewide EMS
      protocols identified from published literature, http://EMSprotocols.org, and each
      state's public health website. MEASUREMENTS: Protocols were reviewed to determine
      whether elder abuse was mentioned, elder abuse was defined, potential indicators
      of elder abuse were listed, management of older adults experiencing abuse was
      described, and instructions regarding reporting were provided. EMS protocols for
      child abuse were reviewed in the same manner for the purpose of comparison.
      RESULTS: Of the 35 publicly available statewide EMS protocols, only 14 (40.0%)
      mention elder abuse. Of protocols that mention elder abuse, 6 (42.9%) define
      elder abuse, 10 (71.4%) describe indicators of elder abuse, 8 (57.1%) provide
      instruction regarding management, and 12 (85.7%) provide instruction regarding
      reporting. Almost twice as many states met each of these metrics for child abuse.
      CONCLUSION: Statewide EMS protocols for elder abuse vary in regard to
      identification, management, and reporting, with the majority of states having no
      content on this subject. Expansion and standardization of protocols may increase
      the identification of elder abuse.

PMID- 29566430
TI  - Use of Antiepileptic Drugs and Dementia Risk-an Analysis of Finnish Health
      Register and German Health Insurance Data.
AB  - OBJECTIVES: To evaluate the association between regular antiepileptic drug (AED)
      use and incident dementia. DESIGN: Case-control analysis. SETTING: Finnish public
      health register and German health insurance data. PARTICIPANTS: Individuals with
      dementia of any type (German data, N=20,325) and Alzheimer's disease (AD; Finnish
      data, N=70,718) were matched with up to four control persons without dementia.
      MEASUREMENTS: We analyzed the association between regular AED use and dementia.
      To address potential protopathic bias, a lag time of 2 years between AED use and
      dementia diagnosis was introduced. Odds ratios (ORs) were calculated by applying
      conditional logistic regression, adjusted for potential confounding factors such
      as comorbidities and polypharmacy. RESULTS: Regular AED use was more frequent in
      individuals with dementia than controls. Regular use of AEDs was associated with
      a significantly greater risk of incident dementia (adjusted OR=1.28, 95%
      confidence interval (CI)=1.14-1.44) and AD (adjusted OR=1.15, 95% CI=1.09-1.22)
      than no AED use. We also detected a trend toward greater risk of dementia with
      higher exposure. When AEDs with and without known cognitive adverse effects
      (CAEs) were compared, a significantly greater risk of dementia was observed for
      substances with known CAEs (dementia: OR=1.59, 95% CI=1.36-1.86; AD: OR=1.19, 95%
      CI=1.11-1.27). CONCLUSION: AEDs, especially those with known CAEs, may contribute
      to incident dementia and AD in older persons.

PMID- 29566431
TI  - Dental size variability in Central African Pygmy hunter-gatherers and Bantu
      speaking farmers.
AB  - OBJECTIVES: Odontometric studies of African populations show high within-group
      variation in tooth size. Overall, North Africans exhibit smaller dimensions than
      groups from eastern and southern sub-Saharan regions, but no previous studies
      have analyzed the full dental metrics among extant African Pygmy hunter-gatherers
      and Bantu-speaking farmers. Furthermore, the population variability in tooth
      crown sizes from equatorial rainforest regions remains to be elucidated.
      MATERIALS AND METHODS: The mesiodistal and buccolingual diameters of the
      permanent teeth (I1-M2) were measured in vivo using high-resolution replicas from
      Baka Pygmies and Mvae and Yassa Bantu-speakers from Cameroon (western Africa).
      Analyses of variance were used to record sex-related and population-level
      differences in tooth sizes, and a principal component analysis of geometrically
      scaled measures was used to plot the odontometric variability among groups.
      RESULTS: Cameroonian Baka Pygmies differ in dental size from their Bantu-speaking
      neighbors. Molar teeth are larger in Pygmies than in Bantu individuals, while the
      anterior dentition is larger in the Bantu. Baka males exhibit significantly
      larger teeth than females, whereas sexual dimorphism in non-Pygmies is only
      present in the anterior dentition. DISCUSSION: Odontometric patterns and the
      degree of sexual dimorphism in dental size differ among Central African groups,
      indicating adaptation to their different forager and farmer lifestyles. In
      particular, the admixture of Bantu-speakers in Baka populations is smaller than
      that in other western Pygmy groups. The greater dental phenetic diversity in Baka
      compared to that of the smaller-toothed farmers suggests that ecogenetic and
      microevolutionary factors are influencing a particular divergence scenario.

PMID- 29566432
TI  - The timing and causes of a unique chimpanzee community fission preceding Gombe's
      "Four-Year War".
AB  - OBJECTIVES: While permanent group fissions are documented in humans and other
      primate species, they are relatively rare in male philopatric primates. One of
      the few apparent cases occurred in 1973 in Gombe National Park, Tanzania, when a
      community of chimpanzees split into two separate groups, preceding the famous
      "Four-Year War." We tested the hypothesis that the original group was a single
      cohesive community that experienced permanent fission, and investigated several
      potential catalysts. MATERIALS AND METHODS: We calculated association, grooming,
      and ranging metrics from historical data and used community detection algorithms
      and matrix permutation tests to determine the timing, dynamics, and causes of
      changes in social network subgrouping structure. RESULTS: We found that the two
      communities indeed split from one cohesive community, albeit one with incipient
      subgrouping. The degree of subgrouping in grooming and association networks
      increased sharply in 1971 and 1972, a period characterized by a dominance
      struggle between three high-ranking males and unusually high male:female sex
      ratios. Finally, we found a relationship between post-split community membership
      and previous association, grooming and ranging patterns in most periods of
      analysis, one that became more pronounced as the fission approached. DISCUSSION:
      Our analysis suggests that the community began to split during a time of an
      unusually male-biased sex ratio and a protracted dominance struggle, and that
      adult males remained with those with whom they had preferentially associated
      prior to the split. We discuss the costs and benefits of group membership in
      chimpanzees and contrast these results with group fissions in humans and other
      taxa.

PMID- 29566433
TI  - Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin
      study.
AB  - The association between diabetes and cancer risk remains controversial. Hence, we
      examined whether midlife diabetes is related to the risk of cancer in late-life,
      and whether genetic and early-life environmental factors play a role in this
      association. This study included 25,154 twin individuals born in 1958 or earlier
      from the Swedish Twin Registry. Information on cancer diagnosis in late life
      (aged >= 65) during 1998-2014, was derived from the National Patient and Cancer
      Registries. Diabetes was ascertained based on self- or informant-reported
      history, patient registry and antidiabetic medication use. Midlife diabetes was
      defined when diabetes was diagnosed before 65 years. Data were analyzed following
      two strategies: (i) unmatched case-control analysis for all participants using
      generalized estimating equation (GEE) models, and (ii) co-twin control analysis
      for cancer-discordant twin pairs using conditional logistic regression. Overall,
      1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In
      multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95
      37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37
      (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people
      with diabetes, diabetes duration was dose-dependently associated with cancer
      risk. In conditional logistic regression analysis of 176 prostate cancer
      discordant twin pairs, the association between midlife diabetes and prostate
      cancer in later life became stronger. Midlife diabetes increases the risk of
      pharynx, small intestine and liver cancers, but reduces prostate cancer risk in
      late life. Genetic and early-life environmental factors may partially contribute
      to the diabetes-prostate cancer association.

PMID- 29566434
TI  - Design, synthesis, and neuroprotective effects of dual-brain targeting naproxen
      prodrug.
AB  - A new dual-targeting naproxen prodrug conjugated with glucose and ascorbic acid
      for central nervous system (CNS) drug delivery was designed and synthesized in
      order to effectively deliver naproxen to the brain. Naproxen could be released
      from the prepared prodrugs when incubated with various buffers, mouse plasma, and
      brain homogenate. Also, the prodrug showed superior neuroprotective effect in
      vivo over naproxen. Our results suggest that chemical modification of
      therapeutics with warheads of glucose and ascorbic acid represents a promising
      and efficient strategy for the development of brain targeting prodrugs by
      utilizing the endogenous transportation mechanism of the warheads.

PMID- 29566435
TI  - Anaemia and thyrotoxicosis: The need to look for an alternative cause.
AB  - OBJECTIVES: Anaemia and thyrotoxicosis are both relatively common. It is unclear
      whether thyrotoxicosis results in anaemia in the absence of other causes. The aim
      of this study was to determine the prevalence and characteristics of anaemia in
      patients with thyrotoxicosis. DESIGN: A prospective cohort study of patients with
      thyrotoxicosis. PATIENTS: 353 patients referred to a regional endocrinology
      centre in New Zealand from March 2013 to November 2014 for new-onset
      thyrotoxicosis. MEASUREMENTS: Detailed assessment including thyroid function
      tests, full blood count, inflammatory markers, haematological parameters and
      coeliac serology. Anaemia was defined as a haemoglobin value <115 g/L (woman) or
      <130 g/L (men). RESULTS: Anaemia was present in 31 (8.7%) patients at diagnosis.
      Of these, pre-existing anaemia was present in 10, and a further 11 had one or
      more identifiable underlying cause(s) for the anaemia. Only 10 patients (2.8% of
      the entire cohort) had anaemia not clearly attributable to another cause. Median
      free thyroid hormone levels were higher in those with anaemia of unknown cause
      compared to patients with thyrotoxicosis alone. The median duration of anaemia
      was shorter in patients with thyrotoxicosis-associated anaemia compared to those
      with anaemia due to an underlying cause (1 vs 6 months, P = .001). In all
      patients with thyrotoxicosis-associated anaemia, the anaemia resolved, either
      prior to, or on becoming euthyroid. CONCLUSION: Anaemia coexisting with
      thyrotoxicosis is less common than previously reported and is mild and transient.
      Patients with thyrotoxicosis and significant anaemia should be investigated for
      other potential causes, particularly when anaemia persists.

PMID- 29566436
TI  - Auscultation of respiratory sounds: how to practise, how to teach?

PMID- 29566437
TI  - Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary
      neurohormonal axes.
AB  - BACKGROUND: Bimagrumab is a human monoclonal antibody inhibitor of activin type
      II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking
      binding of myostatin and other negative regulators of muscle growth. Bimagrumab
      is under evaluation for muscle wasting and associated functional loss in hip
      fracture and sarcopenia, and in obesity. Bimagrumab also blocks other endogenous
      ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary,
      gonads and adrenal glands. AIM: To evaluate the effect of bimagrumab on the
      pituitary-gonadal and pituitary-adrenal axes in humans. METHODS: Healthy men and
      women, aged 55 to 75 years, received bimagrumab intravenously 10 mg/kg or placebo
      on Day 1 and Day 29. Pituitary-gonadal and pituitary-adrenal functions were
      evaluated with basal hormone measurement and standard gonadotropin-releasing
      hormone (GnRH) and adrenocorticotropic hormone (ACTH) stimulation tests at
      baseline, Week 8 and at the end of study (EOS)-Week 20. RESULTS: At Week 8,
      follicle-stimulating hormone (FSH) levels were reduced by 42.16 IU/L (P < .001)
      and luteinizing hormone (LH) levels were increased by 2.5 IU/L (P = .08) over
      placebo in response to bimagrumab in women but not in men. Effects that were
      reversible after bimagrumab was cleared. Gonadal and adrenal androgen levels were
      not affected by exposure to bimagrumab. CONCLUSION: Bimagrumab alters the
      function of pituitary gonadotroph cells, consistent with blockade of activin on
      local ActRII. This effect is reversible with clearance of bimagrumab. Bimagrumab
      did not impact gonadal and adrenal androgen secretion.

PMID- 29566438
TI  - Rene Laennec and the origins of the stethoscope.

PMID- 29566439
TI  - Comparison of two melphalan protocols and evaluation of outcome and prognostic
      factors in multiple myeloma in dogs.
AB  - BACKGROUND: Multiple myeloma (MM) in dogs typically is treated with melphalan. A
      daily melphalan dosing schedule reportedly is well tolerated and associated with
      favorable outcome. Although anecdotally a pulse dose regimen has resulted in
      successful responses, little long-term outcome and safety data is available
      regarding this dosing regimen for dogs with MM. HYPOTHESIS/OBJECTIVES: (1) To
      compare outcome and adverse event profiles between pulse dose and daily dose
      melphalan schedules and (2) to report prognostic factors in dogs with MM treated
      with melphalan. We hypothesized that both protocols would have similar outcomes
      and tolerability. ANIMALS: Thirty-eight client-owned dogs diagnosed with MM
      receiving pulse dose (n = 17) or daily dose (n = 21) melphalan. METHODS:
      Retrospective cohort study assessing outcome and adverse events in dogs receiving
      either protocol. Risk factors were evaluated for their prognostic relevance.
      RESULTS: Both regimens were well tolerated and similarly effective, with an
      overall median survival time of 930 days. Renal disease and neutrophil-to
      lymphocyte ratio (NLR) were negative prognostic factors, whereas hypercalcemia
      and osteolytic lesions were not prognostic factors in this study population.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Positive results support the use of either
      dosing regimen for the treatment of dogs with MM, and renal disease and NLR were
      negative prognostic factors. Prospective, controlled, and randomized studies are
      warranted to confirm these findings.

PMID- 29566440
TI  - Transcranial magnetic motor evoked potentials and magnetic resonance imaging
      findings in paraplegic dogs with recovery of motor function.
AB  - BACKGROUND: Transcranial magnetic motor evoked potentials (TMMEP) are associated
      with severity of clinical signs and magnetic resonance imaging (MRI) findings in
      dogs with spinal cord disease. HYPOTHESIS: That in initially paraplegic dogs with
      thoracolumbar intervertebral disc herniation (IVDH), MRI findings before surgery
      and TMMEPs obtained after decompressive surgery are associated with long-term
      neurological status and correlate with each other. ANIMALS: Seventeen client
      owned paraplegic dogs with acute thoracolumbar IVDH. METHODS: Prospective
      observational study. TMMEPs were obtained from pelvic limbs and MRI (3T) of the
      spinal cord was performed at initial clinical presentation. Follow-up studies
      were performed <= 2 days after reappearance of motor function and 3 months later.
      Ratios of compression length, intramedullary hyperintensities' length (T2
      weighted hyperintensity length ratio [T2WLR]), and lesion extension (T2-weighted
      lesion extension ratio) in relation to the length of the 2nd lumbar vertebral
      body were calculated. RESULTS: TMMEPs could be elicited in 10/17 (59%) dogs at
      1st and in 16/17 (94%) dogs at 2nd follow-up. Comparison of TMMEPs of 1st and 2nd
      follow-up showed significantly increased amplitudes (median from 0.19 to 0.45 mV)
      and decreased latencies (from 69.38 to 40.26 ms; P = .01 and .001, respectively).
      At 2nd follow-up latencies were significantly associated with ambulatory status
      (P = .024). T2WLR obtained before surgery correlated with latencies at 2nd follow
      up (P = .04). CONCLUSIONS: TMMEP reflect motor function recovery after severe
      spinal cord injury.

PMID- 29566441
TI  - All-cause mortality rates and home deaths decreased in children with life
      limiting diagnoses in Denmark between 1994 and 2014.
AB  - AIM: Specialised paediatric palliative care has not previously been a priority in
      Denmark. The aim of this study was to support its development and organisation,
      by examining why and where children died using official national data for 1994
      2014. METHODS: We obtained data on 9462 children who died before the age of 18
      from the Danish Register of Causes of Death. The causes of deaths were listed
      according to the codes in the International Classification of Diseases. RESULTS:
      The all-cause mortality rate decreased by 52% over the study period, and infants
      below one year accounted for 61% of all deaths. The decline in infant mortality
      (26%) primarily reflected fewer deaths due to congenital malformations and
      chromosomal abnormalities (68%) and perinatal deaths (30%). In children aged one
      year to 17 years, the substantial decrease (65%) was due to external causes (75%)
      and neoplasms (57%). The relative proportion of hospital deaths increased, while
      home deaths decreased. CONCLUSION: All-cause mortality rate decreased markedly,
      and the relative proportion of hospital deaths increased. The results may reflect
      more aggressive and effective treatment attempts to save lives, but some
      terminally ill children may be deprived of the option of dying at home.

PMID- 29566443
TI  - Effects of montmorency tart cherry (L. Prunus Cerasus) consumption on nitric
      oxide biomarkers and exercise performance.
AB  - The purpose of this study was to investigate the effects of Montmorency tart
      cherry juice (MC) on nitric oxide (NO) biomarkers, vascular function, and
      exercise performance. In a randomized, double-blind, placebo (PLA)-controlled,
      crossover study, 10 trained cyclists (mean +/- SD; VO2peak 59.0 +/- 7.0
      mL/kg/min) acutely ingested 30 mL of either MC or PLA following dietary
      restrictions of polyphenol-rich compounds and completed 6-minutes moderate- and
      severe-intensity cycling bouts 1.5 hour post-ingestion on 2 occasions for each
      experimental condition. The severe-intensity cycling test was continued to
      exhaustion on 1 occasion and immediately followed by a 60-seconds all-out sprint
      on the other occasion. Blood pressure, pulse wave measures, tissue oxygenation
      index, and plasma nitrite concentration were assessed pre- and 1.5 hour post
      ingestion. Time to exhaustion was not different between conditions (P > .05), but
      peak power over the first 20 seconds (363 +/- 42 vs 330 +/- 26 W) and total work
      completed during the 60-seconds all-out sprint (21 +/- 3 vs 19 +/- 3 kJ) were 10%
      higher in the MC trial compared to the PLA trial (P < .05). Systolic blood
      pressure was 5 +/- 2 mm Hg lower 1.5 hour post-MC supplementation compared to PLA
      supplementation (P < .05). There were no differences in pulse wave measures,
      plasma nitrite concentration, or tissue oxygenation between the MC and PLA trials
      (P > .05). These results suggest that acute supplementation with MC can lower
      blood pressure and improve some aspects of exercise performance, specifically end
      sprint performance, in trained cyclists.

PMID- 29566444
TI  - Clinical significance of tumor mitotic rate and lack of epidermal attachment in
      melanoma of the head and neck.
AB  - BACKGROUND: The primary purpose of this study was to identify the prognostic role
      of primary dermal melanoma and tumor mitotic rate in melanomas of the head and
      neck. METHODS: A retrospective review of the histopathologic, clinical, and
      demographic data of 256 patients was performed to investigate the impact of
      primary dermal melanoma and tumor mitotic rate on sentinel lymph node positivity,
      recurrence, and 5-year overall and disease-free survival. RESULTS: Increased
      tumor mitotic rate, but not primary dermal melanoma, is a significant predictor
      of sentinel lymph node positivity and higher likelihood of recurrence. Survival
      analysis demonstrated that both increased tumor mitotic rate and primary dermal
      melanoma decreased the 5-year overall and disease-free survival rates of patients
      with head and neck melanoma lesions. CONCLUSION: Tumor mitotic rate and primary
      dermal melanoma may have prognostic significance for both overall and disease
      free survival in patients with head and neck melanoma. A larger prospective study
      is warranted to further elucidate prognostic factors for melanoma in the head and
      neck region.

PMID- 29566442
TI  - ACVIM consensus update on Lyme borreliosis in dogs and cats.
AB  - An update of the 2006 American College of Veterinary Internal Medicine (ACVIM)
      Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment,
      and Prevention was presented at the 2016 ACVIM Forum in Denver, CO, followed by
      panel and audience discussion and a drafted consensus statement distributed
      online to diplomates for comment. The updated consensus statement is presented
      below. The consensus statement aims to provide guidance on the diagnosis,
      treatment, and prevention of Lyme borreliosis in dogs and cats.

PMID- 29566445
TI  - A [4+2] Condensation Strategy to Imine-Linked Single-Crystalline Zeolite-Like
      Zinc Phosphate Frameworks.
AB  - Double-4-ring zinc phosphate (D4R), [Zn(dipp)(4-Py-CHO)]4 (2)
      (dipp=diiminopyridine), bearing four formyl groups, has been utilized as a
      building block (SBU) for the synthesis of a new class of imine-linked [4+2] COF
      like polycrystalline zinc phosphate frameworks. Reactions of 2 with a series of
      linear aromatic diamines results in the formation of polycrystalline frameworks
      [Zn4 (dipp)4 (L)2 ]n (3-6) (L=L1 to L4 , diimines formed by condensation of 4
      pyridine carboxaldehyde with diamines). Employing an alternative synthetic
      strategy, through a diffusion-controlled slow reaction of 2 with the pre
      synthesized 4,4'-bispyridyl bisimine (L3 ), [Zn4 (dipp)4 (L3 )2 ]n (5') has been
      obtained as single crystals. Complex 5' is a 3D-framework, exhibiting a rare
      eightfold interpenetrated diamondoid network. The long spacer length (19.6 A)
      results in extensive entanglement in 5'. Powder diffraction data suggest that
      these compounds are isoreticular 3D-frameworks. To study the effect of the
      relative position of pyridyl donors with respect to the central benzidine moiety,
      3,3'-bispyridyl bisimine (L5 ) was investigated as the spacer. A slow reaction of
      1 b with L5 leads to the isolation of a 2D-boxed-sheet coordination polymer [Zn4
      (dipp)4 (L5 )2 ]n (7). Selective formation of 3D-framework 5' from L3 and the 2D
      framework 7 from L5 is due to the angles created by the coordination of para- and
      meta-pyridyl nitrogen centers at the zinc centers of the D4R cubane. Compound 5'
      has been utilized as a catalyst for Knoevenagel condensation.

PMID- 29566446
TI  - Polymorphism of regulatory region of GHRL gene (-2531C>T) as a promising
      predictive factor for radiotherapy-induced oral mucositis in patients with head
      neck cancer.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      single nucleotide polymorphisms (SNP; rs1629816) in the regulatory region (c.
      2531C>T) of the ghrelin (GHRL) gene and the occurrence and severity of oral
      mucositis caused by radiotherapy (RT) in patients with head and neck cancer.
      METHODS: Oral mucositis in 65 patients with head and neck cancer who underwent
      irradiation were assessed according to Radiation Therapy Oncology Group
      (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) scale.
      The DNA from patients with head and neck cancer was isolated from whole blood.
      The genotypes were determined using the minisequencing method (SNaPshot PCR).
      RESULTS: The frequency of occurrence of the GHRL gene (c.-2531C>T, rs1629816)
      genotypes were as follows: AA = 21.5%; GA = 40%; and GG = 38.5%. In case of AA
      genotype, there was a 7-fold decrease of the risk of occurrence of oral mucositis
      (of grades 2 and 3) in the sixth week of RT (AA vs GA or GG, respectively: 17.9%
      vs 82.1% patients; odds ratio [OR] 0.14; 95% confidence interval [CI] 0.02-0.98;
      P = .0481). No statistically significant differences were observed between the
      volume of oral cavity contours (V30, V40, and V50) depending on the GHRL genotype
      in patients with head and neck cancer. CONCLUSION: The study results have
      demonstrated an association between the AA genotype of the GHRL gene and the risk
      of more severe oral mucositis attributed to RT in patients with head and neck
      cancer.

PMID- 29566447
TI  - Posterior auricular artery as a novel anatomic landmark for identification of the
      facial nerve: A cadaveric study.
AB  - BACKGROUND: Despite preservation techniques, performing a parotidectomy carries a
      transient facial nerve dysfunction rate in up to 65% of cases and a permanent
      facial nerve weakness rate of 4%-7%. METHODS: The lateral aspect of the face and
      neck was exposed in 5 cadaveric heads (10 sides). The relationship of the
      posterior auricular artery (PAA) and the facial nerve was studied and recorded
      and descriptive measurements were taken. RESULTS: In all specimens, the facial
      nerve trunk crossed the PAA inferior to the stylomastoid foramen and could be
      identified precisely by tracing the PAA proximally. The distance from the cross
      point of the PAA and the facial nerve to the external meatal cartilage was 5.2 +/
      0.2 mm. CONCLUSION: The PAA represents a potential new anatomic landmark for
      facial nerve identification at the main trunk.

PMID- 29566448
TI  - Evaluation of a rehabilitation planning consult for survivors of head and neck
      cancer.
AB  - BACKGROUND: The rehabilitation planning consult (RPC) is a novel,
      transdisciplinary rehabilitation intervention for survivors of head and neck
      cancer. The study aimed to: (1) estimate recruitment and withdrawal rates, and
      adverse events; and (2) estimate the effect on rehabilitation indicators in
      survivors of head and neck cancer. METHODS: A single group pre-post study with
      follow-up was conducted with survivors of head and neck cancer who had completed
      treatment within 18 months. Outcome measures included goal attainment and quality
      of life indicators. RESULTS: Thirty participants (30) completed the RPC, and 20
      completed follow-up. The average age was 59.8 years (SD 13.3), 23 were men, and
      23 set rehabilitation goals. At follow-up, there was a large effect on goal
      performance (d = 1.5) and satisfaction (d = 1.5), and on the Short Form Health
      Survey-36 (SF-36) physical role and social functioning subscales (d = 1.0 and
      0.8). There was a small to moderate effect on most other outcomes. CONCLUSION:
      The RPC is a promising transdisciplinary rehabilitation intervention warranting
      further study with a controlled trial.

PMID- 29566450
TI  - Segmentation of gray matter, white matter, and CSF with fluid and white matter
      suppression using MP2RAGE.
AB  - BACKGROUND: MP2RAGE can generate uniform T1 -weighted images, which have been
      used for brain segmentation. However, there remain concerns about carrying out
      fast brain segmentation. PURPOSE: To propose an acquisition-based method for fast
      segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid
      (CSF) of healthy human brains with fluid and white matter suppression (FLAWS)
      using MP2RAGE. STUDY TYPE: Prospective. SUBJECTS: 12 volunteers (23-28 years,
      seven subjects; 51-62 years, five subjects). FIELD STRENGTH/SEQUENCES: 3T/3D
      MPRAGE and FLAWS. ASSESSMENT: The proposed method was evaluated by calculating
      tissue volumes and the spatial overlap with the segmentation results from FSL and
      SPM12. The processing time was recorded. STATISTICAL TESTS: A paired t-test was
      used to compare the tissue volumes of the proposed method with those from other
      segmentation methods RESULTS: For the 12 subjects, the tissue volume difference
      between the proposed and SPM12 were 3.2 +/- 2.8%, 4.2 +/- 2.5%, 18.2 +/- 13.1%
      for GM, WM, and CSF, respectively. The relative difference between the proposed
      and FSL was over 14% for all tissue classes. The spatial overlap between the
      proposed and other methods were 87-94% for GM and WM and less than 80% for CSF.
      The GM and WM volumes of the proposed method were not significantly different
      from those of SPM12 using MPRAGE as the input (P = 0.5540 and P = 0.3115,
      respectively). The rest of the comparisons all showed significant differences
      between the proposed and other methods. Statistical analysis of the two subgroups
      yielded similar results. The mean processing time of one subject was 6.5, 185,
      and 165 seconds for the proposed method, FSL, and SPM12, respectively. DATA
      CONCLUSION: Our method may be accurate for the segmentation of most brain
      structures using FLAWS. In addition, the proposed method is fast and applicable
      to the two distinct age ranges. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1
      J. Magn. Reson. Imaging 2018;48:1540-1550.

PMID- 29566449
TI  - Quantitative susceptibility mapping (QSM) minimizes interference from cellular
      pathology in R2* estimation of liver iron concentration.
AB  - BACKGROUND: A challenge for R2 and R2* methods in measuring liver iron
      concentration (LIC) is that fibrosis, fat, and other hepatic cellular pathology
      contribute to R2 and R2* and interfere with LIC estimation. PURPOSE: To examine
      the interfering effects of fibrosis, fat, and other lesions on R2* LIC estimation
      and to use quantitative susceptibility mapping (QSM) to reduce these distortions.
      STUDY TYPE: Prospective. PHANTOMS, SUBJECTS: Water phantoms with various
      concentrations of gadolinium (Gd), collagen (Cl, modeling fibrosis), and fat;
      nine healthy controls with no known hepatic disease, nine patients with known or
      suspected hepatic iron overload, and nine patients with focal liver lesions.
      FIELD STRENGTH/SEQUENCE: The phantoms and human subjects were imaged using a 3D
      multiecho gradient-echo on clinical 1.5T and 3T MRI systems. ASSESSMENT: QSM and
      R2* images were postprocessed from the same gradient-echo data. Fat contributions
      to susceptibility and R2* were corrected in signal models for LIC estimation.
      STATISTICAL TESTS: Polynomial regression analyses were performed to examine
      relations among susceptibility, R2* and true [Gd] and [Cl] in phantoms, and among
      susceptibility and R2* in patient livers. RESULTS: In phantoms, R2* had a strong
      nonlinear dependency on [Cl], [fat], and [Gd], while susceptibility was linearly
      dependent (R2  > 0.98). In patients, R2* was highly sensitive to liver
      pathological changes, including fat, fibrosis, and tumors, while QSM was
      relatively insensitive to these abnormalities (P = 0.015). With moderate iron
      overload, liver susceptibility and R2* were not linearly correlated over a common
      R2* range [0, 100] sec-1 (P = 0.35). DATA CONCLUSION: R2* estimation of LIC is
      prone to substantial nonlinear interference from fat, fibrosis, and other
      lesions. QSM processing of the same gradient echo MRI data can effectively
      minimize the effects of cellular pathology. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1069-1079.

PMID- 29566451
TI  - Dental implications in Hajdu-Cheney syndrome: A novel case report and review of
      the literature.
AB  - OBJECTIVE: To identify the molecular genetic etiology of an individual with a
      dysmorphic face, unusual teeth mobility, and root resorption. SUBJECTS AND
      METHODS: DNA samples were collected from a trio of family members, and whole
      exome sequencing was performed. RESULTS: Mutational analysis revealed a de novo
      mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would
      introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein
      without C-terminus, escaping from the nonsense-mediated decay system. Sanger
      sequencing confirmed that this mutation was generated spontaneously. CONCLUSIONS:
      In this study, we identified a novel nonsense mutation in the last exon of the
      NOTCH2 gene causing Hajdu-Cheney syndrome. We described the genotype and
      phenotype correlation and the related dental complications. These results will
      advance the understanding of the NOTCH2 signaling in periodontitis and root
      resorption.

PMID- 29566452
TI  - Analysis of circulating tumor DNA does not improve the clinical management of
      patients with locally advanced and metastatic papillary thyroid carcinoma.
AB  - BACKGROUND: Circulating cell-free tumor DNA (ctDNA) in plasma is a promising
      noninvasive instrument for cancer monitoring. Detection of BRAFV600E on ctDNA of
      patients with papillary thyroid carcinoma (PTC) may represent an indicator of
      tumor aggressiveness and progression. METHODS: Eighty-three plasma samples were
      collected from 70 patients with thyroid nodules undergoing surgery and from 13
      patients with PTC causing distant metastases. A total of 59 PTCs from both groups
      were evaluated for BRAF mutation on tumor tissue and on ctDNA from plasma samples
      by real-time polymerase chain reaction (PCR) and digital PCR. RESULTS: Of 59
      PTCs, 22 were BRAFV600E mutated (37.3%). The corresponding ctDNA was negative by
      using both techniques. CONCLUSION: Although highly sensitive techniques were
      used, in our study, circulating BRAFV600E alleles were never detected in the
      plasma of patients with PTC; therefore, our results raise the question about the
      clinical usefulness of BRAFV600E analysis on ctDNA of patients with PTC.

PMID- 29566453
TI  - Analysis of state laws on informed consent for clinical genetic testing in the
      era of genomic sequencing.
AB  - This article assesses the adequacy of informed consent to clinical genetic
      testing laws based on an examination of 15 states with institutions that had been
      involved in a National Institutes of Health-supported Clinical Sequencing
      Exploratory Research Consortium project. We identified relevant statutory
      provisions through a legal search engine and included statutes that describe the
      informed consent requirements for clinical genetic testing and/or the protections
      for genetic material, information, or data. We found that statutory definitions
      were often limited in problematic ways, such as focusing only on variants known
      to be associated with disease or negative health effects or associated with
      asymptomatic disease. Some statutes required complex levels of detail if applied
      to genomic technologies and set confusing disclosure standards for current use
      and future access. Others had exceptions from informed consent requirements for
      future research use, limited requirements for the destruction of specimens as
      opposed to derived data, or linked key definitional components to the evolving
      concept of "identifiability." Further reform and research are needed to ensure
      that state law protections advance as rapidly as the science they aspire to
      enable.

PMID- 29566454
TI  - Bringing Nanotubes into Line.
AB  - Science is ART! The recently published alignment relay technique (ART) is
      summarized. The new method for two-dimensional liquid crystal imprinting allows
      for the alignment of molecules and materials on oxide surfaces.

PMID- 29566455
TI  - Determination of organophosphate flame retardants in soil and fish using
      ultrasound-assisted extraction, solid-phase clean-up, and liquid chromatography
      with tandem mass spectrometry.
AB  - A solid-liquid extraction method in combination with high-performance liquid
      chromatography and tandem mass spectrometry was developed and optimized for
      extraction and analysis of organophosphorus flame retardants in soil and fish.
      Methanol was chosen as the optimum extraction solvent, not only in terms of
      extraction efficiency, but also for its broader analyte coverage. The subsequent
      clean-up by solid-phase extraction is required to eliminate matrix coextractives
      and reduce matrix effects. Recoveries of the optimized method were 50-121% for
      soil and 47-123% for biota, both with high precision (RSDs <12% in soil and <23%
      in biota). The method limits of detection ranged from 0.06 to 0.20 ng/g dry
      weight and between 0.02 and 0.30 ng/g wet weight for soil and biota samples,
      respectively. However, samples with a high lipid content produce several problems
      as solid-phase extraction cartridge clogging that increase variability and
      analysis time. The method was successfully applied for the determination of
      organophosphorus flame retardants in soil and fish from L'Albufera Natural Park
      (Valencia, Spain). Target compounds were detected in all soil and fish samples
      with values varying from 13.8 to 89.7 ng/g dry weight and from 3.3 to 53.0 ng/g
      wet weight, respectively.

PMID- 29566457
TI  - How frequent and important is behavioral thermoregulation by embryonic reptiles?
AB  - The debate about behavioral thermoregulation inside reptile eggs centers on the
      frequency (and hence, biological significance) of the phenomenon, not about its
      validity. Both sides of the debate agree that large eggs in shallow nests laid in
      sun-exposed soil will experience clines in mean temperature and (especially) diel
      thermal variance; that embryos in the middle phase of development have the
      ability to reposition themselves, and room to do so; and that small changes in
      developmental temperatures can influence offspring fitness. Equally, all
      protagonists agree that thermal clines will be too low in some other kinds of
      nests, and that embryonic repositioning is impossible very early and very late in
      development. Based on an array of other fitness-enhancing behaviors exhibited by
      tetrapod embryos, and general principles for recognizing adaptation, we conclude
      that behavioral thermoregulation inside the egg likely is adaptive in some but
      not all reptile species. We identify productive directions for empirical research
      to resolve points of contention.

PMID- 29566456
TI  - Systematic review of outcome measures following chemoradiotherapy for the
      treatment of anal cancer (CORMAC).
AB  - AIM: Six Phase III randomized trials have determined the effectiveness of
      chemoradiotherapy as primary treatment for anal squamous cell carcinoma (ASCC),
      but outcomes reported in these trials varied widely, hindering evidence
      synthesis. To improve reporting in all future trials, we aim to develop a core
      outcomes set (COS). As the first stage of COS development, we undertook a
      systematic review to summarize the outcomes reported in studies evaluating
      chemoradiotherapy for ASCC. METHOD: Systematic literature searches identified
      studies evaluating radiotherapy or chemoradiotherapy for ASCC. Outcomes and
      accompanying definitions were extracted verbatim and categorized into domains.
      RESULTS: From 5170 abstracts, we identified 95 eligible studies, reporting 1192
      outcomes and 533 unique terms. We collapsed these terms into 86 standardized
      outcomes and five domains: survival; disease activity; life impact [including
      quality of life (QoL)]; delivery of care; and toxicity. The most commonly
      reported domains were survival and disease activity, reported in 74 (86%) and 54
      (62%) studies, respectively. No outcome was reported in every publication. Over
      half (43/86) of the standardized outcome terms were reported in fewer than five
      studies, and 21 (25%) were reported in a single study only. There was wide
      variation in definitions of disease-free survival, colostomy-free survival and
      progression-free survival (PFS). Anal continence was reported in only 35 (41%)
      studies. CONCLUSION: Outcomes reported in studies evaluating chemoradiotherapy
      for ASCC were heterogenous and definitions varied widely. Outcomes likely to be
      important to patients, such as ano-rectal function, toxicity and QoL, have been
      neglected. A COS for future trials will address these issues.

PMID- 29566458
TI  - Chronic Stress and Impulsive Risk-Taking Predict Increases in Visceral Fat over
      18 Months.
AB  - OBJECTIVE: The aim of this study was to examine whether baseline chronic stress
      and impulsive risk-taking synergistically predict changes in visceral fat among
      healthy mothers in an observational, longitudinal, 18-month study. METHODS: A
      prospective cohort of 113 adult women (age, mean +/- SD: 42.83 +/- 4.70; BMI,
      mean +/- SD: 24.86 +/- 4.32; 74%, n = 84 white) completed assessments at baseline
      and 18-month follow-up. Chronically stressed mothers caring for a child with an
      autism spectrum disorder ("caregivers"; n = 72 participants) were compared with
      lower stress mothers caring for a neurotypical child ("controls"; n = 41). This
      study objectively assessed impulsive risk-taking by using the Behavioral Analog
      Risk Task at baseline and assessed visceral fat at baseline and 18-month follow
      up by using bioelectrical impedance (ViScan; Tanita Corporation, Tokyo, Japan).
      RESULTS: The interaction of baseline chronic caregiving stress and impulsive risk
      taking predicted an 18-month change in visceral fat, such that greater impulsive
      risk-taking was associated with greater 18-month increases in visceral fat among
      caregivers (beta = 0.423; P = 0.005) but not among controls (beta = -0.030; P =
      0.802), both in unadjusted models and after accounting for covariates. Neither
      chronic stress nor impulsive risk-taking independently predicted 18-month changes
      in visceral fat. CONCLUSIONS: The combination of high chronic stress and high
      impulsive risk-taking may increase risk for visceral fat gain over time and
      therefore may be an important intervention target in obesity prevention.

PMID- 29566459
TI  - Enormous expansion of the chemosensory gene repertoire in the omnivorous German
      cockroach Blattella germanica.
AB  - The acquisition of genome sequences from a wide range of insects and other
      arthropods has revealed a broad positive correlation between the complexity of
      their chemical ecology and the size of their chemosensory gene repertoire. The
      German cockroach Blattella germanica is an extreme omnivore and has the largest
      chemosensory gene repertoire known for an arthropod, exceeding even the highly
      polyphagous spider mite Tetranychus urticae. While the Odorant Receptor family is
      not particularly large, with 123 genes potentially encoding 134 receptors (105
      intact), the Gustatory Receptor family is greatly expanded to 431 genes
      potentially encoding 545 receptors (483 intact), the largest known for insects
      and second only to the spider mite. The Ionotropic Receptor family of olfactory
      and gustatory receptors is vastly expanded to at least 897 genes (604 intact),
      the largest size known in arthropods, far surpassing the 150 known from the
      dampwood termite Zootermopsis nevadensis. Commensurately, the Odorant Binding
      Protein family is expanded to the largest known for insects at 109 genes (all
      intact). Comparison with the far more specialized, but phylogenetically related
      termite, within the Dictyoptera, reveals considerable gene losses from the
      termite, and massive species-specific gene expansions in the cockroach. The
      cockroach has lost function of 11%-41% of these three chemoreceptor gene families
      to pseudogenization, and most of these are young events, implying rapid turnover
      of genes along with these major expansions, presumably in response to changes in
      its chemical ecology.

PMID- 29566461
TI  - Surfactant deficiency syndrome in an infant with a C-terminal frame shift in
      ABCA3: A case report.
AB  - Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory
      distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3
      transports phospholipids into the lamellar bodies of type II alveolar cells, a
      critical step in alveolar surfactant production. We report a term infant with
      ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val)
      mutation in trans with a novel C-terminal frame shift mutation (c.4938delC;
      p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33
      incorrect amino acids. The frame shift spares membrane spanning and nucleotide
      binding domains, but disrupts a highly conserved C-terminal domain, which
      includes sequence motifs necessary for the function of human paralogs ABCA1,
      ABCA4, and the bacterial homolog DrrA. This observation suggests the C-terminal
      domain is also required for normal function of ABCA3.

PMID- 29566460
TI  - Inherently Lean Rats Have Enhanced Activity and Skeletal Muscle Response to
      Central Melanocortin Receptors.
AB  - OBJECTIVE: Activity thermogenesis and energy expenditure (EE) are elevated in
      intrinsically lean rats (high-capacity runners [HCR]) and are also stimulated by
      melanocortin receptor activation in the ventromedial hypothalamus (VMH). This
      study determined whether HCR are more responsive to central modulation of
      activity EE compared with low-capacity runners (LCR). METHODS: HCR and LCR rats
      received intra-VMH microinjections of melanotan II (MTII), a mixed melanocortin
      receptor agonist. Changes in EE, respiratory exchange ratio, activity EE, muscle
      heat, norepinephrine turnover, and muscle energetic modulators were compared.
      RESULTS: HCR were significantly more responsive to intra-VMH MTII-induced changes
      in EE, activity EE, norepinephrine turnover to some muscle subgroups, and muscle
      mRNA expression of some energetic modulators. Though HCR had high muscle activity
      thermogenesis, limited MTII-induced modulation of muscle thermogenesis during
      activity was seen in LCR only. CONCLUSIONS: An inherently lean, high-capacity rat
      phenotype showed elevated response to central melanocortin stimulation of
      activity EE and use of fat as fuel. This may be driven by sympathetic outflow to
      skeletal muscle, which was elevated after MTII. Central melanocortin receptor
      activation also altered skeletal muscle energetic modulators in a manner
      consistent with elevated EE and lowered respiratory exchange ratio.

PMID- 29566462
TI  - Safety profile of blind bronchial sampling-A prospective study in pediatric
      intensive care unit.
AB  - OBJECTIVE: To study the safety profile of blind bronchial sampling in
      mechanically ventilated children. DESIGN: Prospective interventional study.
      SETTING: Tertiary level pediatric intensive care unit of a multispecialty
      hospital. PATIENTS: Children aged 1 month to 16 years on mechanical ventilator
      for >=48 h, were assessed by clinical pulmonary infection score for ventilator
      associated pneumonia (VAP). INTERVENTIONS: Blind bronchial sampling was performed
      following standard procedural guidelines. The hemodynamic, ventilation
      parameters, and arterial blood gases done before, and in next 24 h post procedure
      were recorded and compared. MEASUREMENTS AND MAIN RESULTS: Among the 40 enrolled
      children, VAP was suspected at 5.8 +/- 3.7 days post intubation with
      insignificant increase in median (IQR) PELOD score to 15 (11-23) from 13.5 (11
      23) (P value 0.29). A statistically significant increase in mean blood pressure
      (75.5 +/- 14.7 to 79.1 +/- 14.2, P 0.04) and transient drop in SpO2 (98.2 +/- 2.3
      to 92.2 +/- 9.2, P < 0.001) were noted with insignificant change in heart rate
      (128.7 +/- 25.6 vs 132.0 +/- 30.8, P 0.52), though these variations were
      clinically not significant. There were no major complications like significant
      airway bleed, arrhythmia, air leaks, edema, and change in pulmonary infiltrates
      during the procedure. There were no significant (either clinical or statistical)
      effects of BBS procedure, whether transient or prolonged, on ventilatory
      requirements or gas exchange parameters. CONCLUSIONS: Blind bronchial sampling is
      a safe procedure in children with no major adverse events related to
      hemodynamics, oxygenation, and ventilation parameters.

PMID- 29566463
TI  - Supervised Physical Training Improves Weight Loss After Roux-en-Y Gastric Bypass
      Surgery: A Randomized Controlled Trial.
AB  - OBJECTIVE: Bariatric surgery results in significant weight loss and reduces
      cardiovascular morbidity. However, a large variation in postsurgery weight loss
      is seen. Physical activity promotes weight loss in nonsurgically treated subjects
      with obesity. The aim of this study was to investigate the effects of 6 months of
      supervised physical training following Roux-en-Y gastric bypass surgery (RYGB) on
      body weight and cardiovascular risk markers. METHODS: Sixty participants eligible
      for RYGB were included. Six months post surgery, the participants were randomly
      assigned to either twice-weekly supervised physical training sessions in a
      fitness center (INT) or a control group (CON) for 26 weeks. Before surgery and 6,
      12, and 24 months after surgery, the participants underwent an examination
      program that included anthropometric measurements, blood pressure, heart rate,
      blood samples, and an abdominal computed tomography scan. RESULTS: RYGB
      significantly reduced body weight and improved cardiovascular risk markers (all P
      < 0.01). The supervised physical training intervention resulted in a 4.2-kg (CI: 
      0.2 to -8.3 kg) lower body weight in INT compared with CON at the study end (P =
      0.042). The high-density lipoprotein concentration was significantly higher in
      INT than in CON at the termination of the intervention, but this was not
      maintained at the 24-months examination. CONCLUSIONS: Physical training following
      RYGB improves weight loss and cardiovascular health.

PMID- 29566464
TI  - Why Do Mania and Suicide Occur Most Often in the Spring?

PMID- 29566466
TI  - What Should We Concern in Reporting Conflict of Interest for Submission of
      Manuscript in the Psychiatry Investigation?

PMID- 29566467
TI  - Tarsal switch using an anterior approach to correct severe ptosis.
AB  - BACKGROUND: To present the outcomes of the tarsal switch procedure using an
      anterior approach to correct severe ptosis with poor levator muscle function (<4
      mm) with absent or poor Bell's phenomenon. METHODS: This retrospective case
      series included 11 patients with severe neurogenic or acquired myogenic palpebral
      ptosis. All patients underwent the tarsal switch procedure through an anterior
      approach from 2012 to 2015. Margin reflex distance (MRD1 and MRD2) and the
      palpebral fissure were evaluated preoperatively and postoperatively. Data were
      compared using the Wilcoxon signed-rank test. P-values <0.05 were considered to
      indicate statistical significance. RESULTS: Surgery was performed on 18 eyelids
      (11 patients). The median age at surgery was 57 years (range, 29-86 years). Four
      patients had unilateral ptosis and seven had bilateral ptosis. Nine patients had
      myogenic ptosis and two had neurogenic ptosis. Postoperatively, the chin-up
      position improved in all patients. The MRD1 increased statistically
      significantly, from 0 mm preoperatively to 1.0 mm postoperatively (P=0.001). The
      MRD2 decreased statistically significantly, from 4.5 mm preoperatively to 3.0 mm
      postoperatively (P=0.001). The palpebral fissure did not change (4.0 mm
      preoperatively to 4.0 mm postoperatively) (P=0.13). CONCLUSIONS: The tarsal
      switch procedure through an anterior approach is an effective alternative for
      correcting severe ptosis, especially neurogenic or acquired myogenic ptosis. This
      procedure can be performed with minimal risk of ocular surface exposure and
      provides stable outcomes.

PMID- 29566468
TI  - Lymphatic vessel mapping in the upper extremities of a healthy Korean population.
AB  - BACKGROUND: Intraoperative indocyanine green (ICG) lymphography can effectively
      detect functioning lymph vessels in edematous limbs. However, it is sometimes
      difficult to clearly identify their course in later-stage edematous limbs. For
      this reason, many surgeons rely on experience when they decide where to make the
      skin incision to locate the lymphatic vessels. The purpose of this study was to
      elucidate lymphatic vessel flow patterns in healthy upper extremities in a Korean
      population and to use these findings as a reference for lymphedema treatment.
      METHODS: ICG fluorescence lymphography was performed by injecting 1 mL of ICG
      into the second web space of the hand. After 4 hours, fluorescence images of
      lymphatic vessels were obtained with a near-infrared camera, and the lymphatic
      vessels were marked. Three landmarks were designated: the radial styloid process,
      the mid-portion of the cubital fossa, and the lower border of the deltopectoral
      groove. A straight line connecting the points was drawn, and the distance between
      the connected lines and the marked lymphatic vessels was measured at 8 points.
      RESULTS: There were 30 healthy upper extremities (15 right and 15 left). The
      average course of the main lymph vessels passed 26.0+/-11.6 mm dorsal to the
      styloid process, 5.7+/-40.7 mm medial to the mid-cubital fossa, and 31.3+/-26.1
      mm medial to the three-quarters point of the upper landmark line. CONCLUSIONS:
      The main functioning lymphatic vessel follows the course of the cephalic vein at
      the forearm level, crosses the mid-cubital point, and travels medially toward the
      mid-axilla.

PMID- 29566469
TI  - Volumetric lipoinjection of the fronto-orbital and temporal complex with adipose
      stem cells for the aesthetic restoration of sequelae of craniosynostosis.
AB  - BACKGROUND: Non-syndromic craniosynostosis causes craniofacial asymmetry and may
      persist after cranioplasty. These postoperative asymmetries are primarily
      depressions. In some cases, patients may be subjected to pranks and harassment by
      their peers, affecting their psychosocial development. We propose lipoinjection
      enriched with adipose stem cells (ASCs) to treat the sequelae of craniosynostosis
      in the fronto-orbital and temporal complex in cranioplasty patients, with the
      goal of improving the appearance of the upper third of the face. METHODS: Twelve
      children (four boys and eight girls) between 4 and 8 years of age (mean age, 6
      years) in the postoperative period after treatment for plagiocephaly,
      brachycephaly, and trigonocephaly were included, with a follow-up period of 1 to
      18 months. Fat tissue was obtained from the lower abdomen, and ASCs were isolated
      using the Yoshimura technique. Lipoinjection was performed using several mini
      approaches to ensure adequate distribution. RESULTS: Two different scales were
      used to evaluate the aesthetic outcomes. At 6 months, three plastic surgeons
      independent of the study classified the results using a Likert scale. The
      patients' parents categorized the results using a visual analog scale at 6, 9,
      and 18 months. R esults were favorable on both scales, as the patients' facial
      appearance improved and they reported increased happiness and self-esteem due to
      their remodeled facial appearance. CONCLUSIONS: We suggest that lipoinjection
      enriched with ASCs is a good alternative for correcting asymmetry of the fronto
      orbital and temporal contour in patients with sequelae of craniosynostosis. This
      treatment will help boost patients' self-esteem starting at an early age.

PMID- 29566470
TI  - Management based on grading of animation deformity following implant-based
      subpectoral breast reconstruction.
AB  - Subpectoral breast reconstruction using implants and meshes have been used widely
      in Europe, the United States and the United Kingdom. Although this technique has
      several advantages, animation deformity is a well-documented problem. We propose
      a new grading system to classify breast animation in patients undergoing
      subpectoral implant based breast reconstruction. We also discuss different
      techniques to avoid and correct animation deformity.

PMID- 29566471
TI  - Reduction mammoplasty as a treatment for symptomatic central venous stenosis.
AB  - Central venous stenosis is a rare cause of unilateral breast edema occurring in
      hemodialysis patients that needs to be differentiated from other differential
      diagnoses, including, but not limited to, inflammatory breast carcinoma,
      mastitis, lymphedema, and congestive heart failure. All reports of similar cases
      in the available literature have described improvement or resolution of the edema
      after treatment. Herein, we report and discuss the pathophysiology of breast
      edema formation in a patient who presented with massive left-sided breast edema 7
      years after being diagnosed with central venous stenosis. Medical and minimally
      invasive therapy had not been successful, so she underwent reduction mammoplasty
      to relieve the symptoms.

PMID- 29566472
TI  - [Endoscopic Treatment for Esophageal Cancer].
AB  - Esophageal cancer incidence rate per 100,000 is 4.7 in 2013, which accounts for
      1.1% of the total cancer incidence in Korea. Superficial esophageal squamous cell
      carcinoma is frequently detected in persons undergoing upper endoscopy for
      gastrointestinal symptoms or for gastric cancer screening. Esophagectomy with
      lymph node dissection is the standard treatment for esophageal cancer. However,
      given the considerable morbidity and mortality of esophagectomy, endoscopic
      resection has become the standard of care for most cases of superficial
      esophageal squamous cell carcinoma without metastasis. In addition, endoscopic
      submucosal dissection has increased the cure rate, even when the tumor is large,
      compared to endoscopic mucosal resection. Thus, endoscopic submucosal dissection
      is the treatment of choice for superficial esophageal squamous cell carcinoma
      with a negligible risk of lymph node metastasis. Endoscopic resection is usually
      associated with a low risk of morbidity and no mortality, and has also shown
      favorable long-term outcomes. However, the long-term risk of metastasis remains
      after endoscopic resection, which varies according to the characteristics of
      tumor. This review describes the indication and outcomes of endoscopic resection,
      complications of endoscopic resection, and management after treatment.

PMID- 29566473
TI  - Comparative Study of Esophageal Self-expandable Metallic Stent Insertion and
      Gastrostomy Feeding for Dysphagia Caused by Lung Cancer.
AB  - Background/Aims: Dysphagia is encountered in a large proportion of patients with
      lung cancer and is associated with malnutrition and a poor quality of life. This
      study compared the clinical outcomes of self-expandable metallic stent (SEMS)
      insertion and percutaneous gastrostomy (PG) feeding for patients with lung cancer
      and dysphagia. Methods: A total of 261 patients with lung cancer, who underwent
      either SEMS insertion (stent group) or PG (gastrostomy group) as an initial
      treatment procedure for dysphagia between July 1997 and July 2015 at the Samsung
      Medical Center, were reviewed retrospectively, and 84 patients with esophageal
      obstruction were identified. The clinical outcomes, including the overall
      survival, additional intervention, complications, and post-procedural nutritional
      status in the two groups, were compared. Results: Among the 84 patients finally
      analyzed, 68 patients received SEMS insertion and 16 had PG. The stent group had
      less cervical obstruction and more mid-esophageal obstruction than the
      gastrostomy group. The Kaplan-Meier curves revealed similar overall survival in
      the two groups. Multivariate analysis showed that the two modalities had similar
      survival rates (PG compared with SEMS insertion, hazard ratio 0.682, p=0.219).
      Fifteen patients (22.1%) in the stent group received additional intervention,
      whereas there was no case in the gastrostomy group (p=0.063). The decrease in the
      serum albumin level after the procedure was lower in the gastrostomy group than
      in the stent group (-0.20+/-0.54 g/dL vs. -0.65+/-0.57 g/dL, p=0.013).
      Conclusions: SEMS insertion and PG feeding for relieving dysphagia by lung cancer
      had a comparable survival outcome. On the other hand, PG was associated with a
      better nutritional status.

PMID- 29566474
TI  - Combined Extracts of Artemisia and Green Tea, Mitigated Alcoholic Gastritis Via
      Enhanced Heat-shock Protein 27.
AB  - Background/Aims: Several lines of evidence from epidemiologic and laboratory
      studies have shown that the consumption of Artemisia or green tea extracts (MPGT)
      is inversely associated with the risk of alcohol-induced damage and other chronic
      diseases. Supported by previous studies showing that the combined extract of
      Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti
      inflammatory actions against Helicobacter pylori-associated gastric diseases, it
      was hypothesized that MPGT can offer protection against alcoholic gastritis.
      Methods: Ethanol was administered to induce gastric damage in Wistar rats, which
      had been pretreated with various doses of MPGT, to measure the rescuing action of
      a MPGT pretreatment against ethanol-induced gastric damage. In addition, the
      molecular mechanisms for the preventive effects were examined. Results: The MPGT
      pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric
      damage, which was evidenced by the significant decrease in calcium-dependent
      phospholipase A2, MAPKs, and NF-kappaB levels compared to ethanol alone.
      Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase,
      whereas cyclooxygenase-2 was decreased significantly. All of these biochemical
      changes led to the significant alleviation of alcohol-associated gastric mucosal
      damage. Ethanol significantly increased the TUNEL positivity in the stomach, but
      MPGT decreased the apoptotic index significantly, which was associated with
      significantly lower pathological scores of ethanol-induced mucosal ulcerations.
      The significant protective changes observed alcoholic gastritis with MPGT were
      related to the increased expression of cytoprotective genes, such as heat-shock
      protein (HSP)27, HSP60, and PDGF. Conclusions: The efficient anti-inflammatory,
      anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient
      phytoceutical to rescue the stomach from alcoholic gastritis.

PMID- 29566475
TI  - [Identification of Nodular Gastritis among Patients Diagnosed with
      Lymphofollicular Gastritis on a Gastric Biopsied Specimen].
AB  - Background/Aims: Nodular gastritis (NG) is a well-known endoscopic finding
      observed in patients with a Helicobacter pylori infection, which may lead to
      invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid
      follicles or lymphoid cell aggregates, and is common in children. The aim of this
      study was to identify patients with NG from those in whom gastric biopsied
      specimens showed lymphoid follicles and lymphoid cell aggregates. Methods:
      Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid
      cell aggregates, were included in this study. The inclusion criterion was that
      they underwent a serum pepsinogen assay on the day of upper gastrointestinal
      endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized,
      multiple, colorless subepithelial nodules. Results: Among 108 subjects who showed
      lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on
      endoscopy, and all these subjects showed positive Giemsa staining. Patients
      diagnosed with NG were younger (p=0.012) and showed a female predominance
      (p=0.001) compared to those without NG. The mean serum pepsinogen levels were
      higher (p=0.001) and lymphoid follicle-dominant subjects were more common
      (p<0.001) in the NG subjects than in those without NG. Logistic regression
      analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be
      significant independent risk factors for NG. Conclusions: NG should be
      distinguished from lymphofollicular gastritis because only 12% of patients
      showing gastric biopsy findings of lymphoid follicles and lymphoid cell
      aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more
      common in women and in the younger population, irrespective of the biopsy
      findings and gastric secretory ability.

PMID- 29566476
TI  - Predictors of Malignancies in Patients with Inconclusive or Negative Results of
      Endoscopic Ultrasound-guided Fine-needle Aspiration for Solid Pancreatic Masses.
AB  - Background/Aims: This study analyzed the diagnostic accuracy of endoscopic
      ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in
      patients with or without chronic pancreatitis as well as the clinical parameters
      relevant to a malignancy when EUS-FNA was negative or inconclusive. Methods: A
      total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2
      years at a single institution, were evaluated. All patients underwent EUS-FNA for
      3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final
      diagnosis was obtained by surgery or compatible clinical outcomes for a more than
      12 month follow-up. The diagnostic yields in the patients with or without chronic
      pancreatitis were compared and the histories and laboratory data relevant to
      pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed. Results:
      The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory
      pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74),
      suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The
      diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic
      pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS
      FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical,
      and 5 out of 10 negative cytology cases. The clinical parameters related to a
      pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal
      alkaline phosphatase levels. Conclusions: The diagnostic accuracy of pancreatic
      masses in the background of chronic pancreatitis was low. When EUS-FNA produced
      inconclusive results, the histories of alcohol consumption, pancreatitis, and
      serum levels of alkaline phosphatase are useful for making a final diagnosis.

PMID- 29566477
TI  - Severe Intraperitoneal Hemorrhage from Pseudoaneurysm after a Large-volume
      Paracentesis, Successfully Treated with Microcoil Embolization.
AB  - Large-volume paracentesis-induced intraperitoneal hemorrhage due to
      pseudoaneurysm formation is rarely reported. Here, we present a 56-year-old man
      with alcoholic liver cirrhosis admitted for massive ascites. Large-volume
      paracentesis was performed. Three days later, he became pale and complained of
      dyspnea and abdominal distention with hypotension. Percutaneous iliac angiography
      revealed contrast media leakage from a branch of the left circumflex iliac artery
      with pseudoaneurysm. He was successfully treated with microcoil embolization.
      Several days later, ascitic fluid increased and large-volume paracentesis was
      performed again. Two days later, his hemoglobin level suddenly decreased. An
      abdominal computed tomography scan showed new active bleeding at the left lower
      lateral peritoneal cavity, just anterior to the metalic coils. Percutaneous iliac
      angiography revealed contrast media extravasation from a branch of the left
      inferior epigastric artery with formation of collateral vessel. Percutaneous
      embolization was successfully performed again. After coil embolization, there
      were no further bleeding episodes.

PMID- 29566478
TI  - The Usefulness of Cap-assisted Endoscopic Retrograde Cholangiopancreatography for
      Cannulation Complicated by a Periampullary Diverticulum.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced therapeutic
      procedure to manage choledocholithiasis and pancreatobiliary malignancy. On
      occasion, ERCP failure is encountered due to difficulties in cannulation. We
      assessed the safety and feasibility of cap-assisted ERCP via analyzing cases in
      which cannulation was complicated by periampullary diverticulum. Between November
      2013 and March 2014, ERCP procedures were performed in 346 patients in our
      tertiary medical center. Among the 73 patients who had a periampullary
      diverticulum, conventional ERCP failed in 5 patients due to hidden papilla (n=3)
      or use of tangential approach (n=2). As a rescue method, needle knife fistulotomy
      and selective biliary cannulation using cap-fitted forward-viewing endoscopy were
      successfully used in 4 patients without major complications. Based on our
      experience, cap-fitted forward-viewing endoscopy was relatively easy to measure
      the exact position of papilla and to perform biliary cannulation properly.
      Therefore, we recommend using cap-assisted ERCP by forward-viewing endoscopy as a
      useful and safe alternative to manage patients in whom cannulation is complicated
      by periampullary diverticulum.

PMID- 29566479
TI  - A Prospective Blinded Study of Endoscopic Ultrasound Elastography in Liver
      Disease: Towards a Virtual Biopsy.
AB  - BACKGROUND/AIMS: Liver biopsy has traditionally been used for determining the
      degree of fibrosis, however there are several limitations. Endoscopic ultrasound
      (EUS) real-time elastography (RTE) is a novel technology that uses image
      enhancement to display differences in tissue compressibility. We sought to assess
      whether liver fibrosis index (LFI) can distinguish normal, fatty, and cirrhotic
      liver tissue. METHODS: A total of 50 patients undergoing EUS were prospectively
      enrolled. RTE of the liver was performed to synthesize the LFI in each patient.
      Univariate and multivariable analyses were performed. Chi-square and t-tests were
      performed for categorical and continuous variables, respectively. A p-value of
      <0.05 was considered significant. RESULTS: Abdominal imaging prior to endoscopic
      evaluation suggested normal tissue, fatty liver, and cirrhosis in 26, 16, and 8
      patients, respectively. Patients with cirrhosis had significantly increased mean
      LFI compared to the fatty liver (3.2 vs. 1.7, p<0.001) and normal (3.2 vs. 0.8,
      p<0.001) groups. The fatty liver group showed significantly increased LFI
      compared to the normal group (3.8 vs. 1.4, p<0.001). Multivariable regression
      analysis suggested that LFI was an independent predictor of group features
      (p<0.001). CONCLUSIONS: LFI computed from RTE images significantly correlates
      with abdominal imaging and can distinguish normal, fatty, and cirrhotic-appearing
      livers; therefore, LFI may play an important role in patients with chronic liver
      disease.

PMID- 29566480
TI  - Prediction of Cancer Incidence and Mortality in Korea, 2018.
AB  - PURPOSE: This study aimed to report on cancer incidence and mortality for the
      year 2018 to estimate Korea's current cancer burden. MATERIALS AND METHODS:
      Cancer incidence data from 1999 to 2015 were obtained from the Korea National
      Cancer Incidence Database, and cancer mortality data from 1993 to 2016 were
      acquired from Statistics Korea. Cancer incidence and mortality were projected by
      fitting a linear regression model to observed age-specific cancer rates against
      observed years, then multiplying the projected age-specific rates by the age
      specific population. The Joinpoint regression model was used to determine at
      which year the linear trend changed significantly, we only used the data of the
      latest trend. RESULTS: A total of 204,909 new cancer cases and 82,155 cancer
      deaths are expected to occur in Korea in 2018. The most common cancer sites were
      lung, followed by stomach, colorectal, breast and liver. These five cancers
      represent half of the overall burden of cancer in Korea. For mortality, the most
      common sites were lung cancer, followed by liver, colorectal, stomach and
      pancreas. CONCLUSION: The incidence rate of all cancer in Korea are estimated to
      decrease gradually, mainly due to decrease of thyroid cancer. These up-to-date
      estimates of the cancer burden in Korea could be an important resource for
      planning and evaluation of cancer-control programs.

PMID- 29566481
TI  - Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in
      2015.
AB  - PURPOSE: This study presents the 2015 nationwide cancer statistics in Korea,
      including the incidence, survival, prevalence, and mortality. MATERIALS AND
      METHODS: Cancer incidence data from 1999 to 2015 was obtained from the Korea
      National Cancer Incidence Database and followed until December 31, 2016.
      Mortality data from 1983 to 2015 were obtained from Statistics Korea. The
      prevalence was defined as the number of cancer patients alive on January 1, 2016,
      among all cancer patients diagnosed since 1999. Crude and age-standardized rates
      (ASRs) for incidence, mortality and prevalence and 5-year relative survivals were
      also calculated. RESULTS: Herein, 214,701 and 76,855 Koreans were newly diagnosed
      and died from cancer in 2015, respectively. The ASRs for cancer incidence and
      mortality in 2015 were 258.9 and 82.0 per 100,000, respectively. The overall
      cancer incidence rate has increased significantly by 3.4% annually from 1999 to
      2012, and started to decrease after 2012 (2012-2015, annual percent change, 
      6.1%). However, the overall cancer mortality has decreased 2.7% annually since
      2002. The 5-year relative survival rate for patients diagnosed with cancer
      between 2011 and 2015 was 70.7%, an improvement from the 41.2% for patients
      diagnosed between 1993 and 1995. CONCLUSION: Age-standardized cancer incidence
      rates have decreased since 2012 and mortality rates have declined since 2002;
      however, the 5-year survival rates have improved remarkably from 1993-1995 to
      2011-2015 in Korea.

PMID- 29566482
TI  - What We Talk About When We Talk About Caregiving: The Distribution of Roles in
      Cancer Patient Caregiving in a Family-Oriented Culture.
AB  - Purpose: When it comes to cancer care, the psychological well-being of family
      caregivers has gotten its deserved attention. However, the specific roles that
      the family caregivers take have not been examined as much. The current study
      aimed to investigate the distribution of family caregivers' roles, particularly
      in a family-oriented culture, Korea. Materials and Methods: A sample of 439
      participants was recruited from 11 national and regional cancer centers in Korea.
      The participants who were 60 years old or above went through treatments for their
      gastric, colorectal, or lung cancer. The individual survey included questions
      regarding the family type, living arrangement, and the sources of support when it
      comes to their physical, emotional, financial, and decision-making needs.
      Results: The responses from the participants showed that (1) cancer caregiving is
      shared by multiple family caregivers; (2) the major source of support for elderly
      cancer patients on diverse domains was their spouse; (3) patients' reliance on
      their daughter(s) increased for emotional support; and (4) patients' reliance on
      their son(s) stood out for financial support and decision-making support. Also,
      the older the patients were, the heavier their reliance was on the adult
      children, including sons, daughters, and daughters-in-law. Conclusion: Future
      support programs for elderly cancer patients are suggested to involve multiple
      family caregivers to encourage effective and efficient intervention. Also, the
      limitations of the current study and the suggestions for future research are
      discussed.

PMID- 29566484
TI  - Cluster Assemblies Produced by Aggregation of Preformed Ag Clusters in Ionic
      Liquids.
AB  - Room-temperature ionic liquids (RTILs) can be used as electrosterical stabilizers
      for nanoparticles without adding stabilizing agents. However, the nanoparticle
      stability and its mechanisms are still in discussion. We deposited preformed 2 nm
      +/-0.6 nm silver clusters into the ionic liquid C4MIM PF6 using in situ UV/vis
      absorption to monitor the deposition process. The time- and temperature-dependent
      cluster aggregation process was studied with ex situ UV/vis absorption
      spectroscopy analyzed with electrodynamic calculations using generalized Mie
      theory. On an atomistic level, the sample structure was investigated using EXAFS
      and a neural network based analysis of XANES. The combination of all methods
      shows that an aggregation of the original 2 nm clusters without coalescence takes
      place, which can be controlled or stopped by choosing an appropriate sample
      temperature. This approach allows the controlled production of chainlike cluster
      aggregates in RTIL, promising for a number of applications.

PMID- 29566483
TI  - Sputum Active Polymyxin Lipopeptides: Activity against Cystic Fibrosis
      Pseudomonas aeruginosa Isolates and Their Interactions with Sputum Biomolecules.
AB  - The mucoid biofilm mode of growth of Pseudomonas aeruginosa ( P. aeruginosa) in
      the lungs of cystic fibrosis patients makes eradication of infections with
      antibiotic therapy very difficult. The lipopeptide antibiotics polymyxin B and
      colistin are currently the last-resort therapies for infections caused by
      multidrug-resistant P. aeruginosa. In the present study, we investigated the
      antibacterial activity of a series of polymyxin lipopeptides (polymyxin B,
      colistin, FADDI-003, octapeptin A3, and polymyxin A2) against a panel of
      polymyxin-susceptible and polymyxin-resistant P. aeruginosa cystic fibrosis
      isolates grown under planktonic or biofilm conditions in artificial sputum and
      their interactions with sputum component biomolecules. In sputum media under
      planktonic conditions, the lipopeptides FADDI-003 and octapeptin A3 displayed
      very promising activity against the polymyxin-resistant isolate FADDI-PA066
      (polymyxin B minimum inhibitory concentration (MIC) = 32 mg/L), while retaining
      their activity against the polymyxin-sensitive strains FADDI-PA021 (polymyxin B
      MIC = 1 mg/L) and FADDI-PA020 (polymyxin B MIC = 2 mg/L). Polymyxin A2 was only
      effective against the polymyxin-sensitive isolates. However, under biofilm growth
      conditions, the hydrophobic lipopeptide FADDI-003 was inactive compared to the
      more hydrophilic lipopeptides, octapeptin A3, polymyxin A2, polymyxin B, and
      colistin. Transmission electron micrographs revealed octapeptin A3 caused
      reduction in the cell numbers in biofilm as well as biofilm
      disruption/"antibiofilm" activity. We therefore assessed the interactions of the
      lipopeptides with the component sputum biomolecules, mucin, deoxyribonucleic acid
      (DNA), surfactant, F-actin, lipopolysaccharide, and phospholipids. We observed
      the general trend that sputum biomolecules reduce lipopeptide antibacterial
      activity. Collectively, our data suggests that, in the airways, lipopeptide
      binding to component sputum biomolecules may reduce antibacterial efficacy and is
      dependent on the physicochemical properties of the lipopeptide.

PMID- 29566485
TI  - Structure-Based Discovery of Nonpeptide Allatostatin Analogues for Pest Control.
AB  - FGLamide allatostatins (ASTs) are regarded as possible insecticide candidates,
      although their lack of in vivo effects, rapid degradation, poor water solubility,
      and high production costs preclude their practical use in pest control. In
      contrast to previous research, the C-terminal tripeptide (FGLa) was selected as
      the lead compound in this study. Five nonpeptide AST analogues (2-amino-1-[3-oxo
      3-(substituted-anilino)propyl]pyridinium nitrate derivatives) were designed on
      the basis of the structure-activity relationship and docking results of FGLa. All
      of the nonpeptide analogues (S1-S5) were more potent against juvenile-hormone
      (JH) biosynthesis than the lead compound. They significantly inhibited the
      biosynthesis of JH in vivo following injection. A pest-control application
      demonstrated that S1 and S3 have larvicidal effects following oral administration
      (the IC50 values were 0.020 and 0.0016 mg/g, respectively). The good oral
      toxicities and excellent water solubilities of S1 and S3 suggest that they have
      considerable potential as insecticides for pest management.

PMID- 29566486
TI  - Discovery of Benzenesulfonamide Derivatives as Carbonic Anhydrase Inhibitors with
      Effective Anticonvulsant Action: Design, Synthesis, and Pharmacological
      Evaluation.
AB  - Two series of novel benzenesulfonamide derivatives were synthesized and evaluated
      for their human carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against
      four isoforms, hCA I, hCA II, hCA VII, and hCA IX. It was found that compounds of
      both series showed low to medium nanomolar inhibitory potential against all
      isoforms. Some of these derivatives displayed selective inhibition against the
      epileptogenesis related isoforms hCA II and VII, within the nanomolar range.
      These potent hCA II and VII inhibitors were evaluated as anticonvulsant agents
      against MES and sc-PTZ induced convulsions. These sulfonamides effectively
      abolished induced seizures in both models. Furthermore, time dependent seizure
      protection capability of the most potent compound was also evaluated. A long
      duration of action was displayed, with efficacy up to 6 h after drug
      administration. The compound appeared as an orally active anticonvulsant agent
      without showing neurotoxicity in a rotarod test, a nontoxic chemical profile
      being observed in subacute toxicity study.

PMID- 29566487
TI  - Concurrent In Vitro Synthesis and Functional Detection of Nascent Activity of the
      KcsA Channel under a Membrane Potential.
AB  - Processes involved in the functional formation of prokaryotic membrane proteins
      have remained elusive. Here, we developed a new in vitro membrane protein
      expression system to detect nascent activities of the KcsA potassium channel in
      lipid bilayers under an applied membrane potential. The channel was synthesized
      using a reconstituted Escherichia coli-based in vitro transcription/translation
      system (IVTT) in a water-in-oil droplet lined by a membrane. The synthesized
      channels spontaneously incorporated into the membrane even without the translocon
      machinery (unassisted pathway) and formed functional channels with the correct
      orientation. The single-channel current of the first appearing nascent channel
      was captured, followed by the subsequent appearance of multiple channels.
      Notably, the first appearance time shortened substantially as the membrane
      potential was hyperpolarized. Under a steadily applied membrane potential, this
      system serves as a production line of membrane proteins via the unassisted
      pathway, mimicking the bacterial synthetic membrane.

PMID- 29566488
TI  - Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as
      Potent and Selective BET Inhibitors for Potential Treatment of Castration
      Resistant Prostate Cancer (CRPC).
AB  - The bromodomain and extra-terminal (BET) family proteins have gained increasing
      interest as drug targets for treatment of castration-resistant prostate cancer
      (CRPC). Here, we describe the design, optimization, and evaluation of benzo[
      d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal
      structures of the representative inhibitors in complex with BRD4(1) provided
      solid structural basis for compound optimization. The two most potent compounds,
      6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of
      82 and 81 nM, respectively. They also exhibited high selectivity over other non
      BET subfamily members. The compounds potently inhibited cell growth, colony
      formation, and the expression of AR, AR regulated genes, and MYC in prostate
      cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a
      C4-2B CRPC xenograft tumor model in mice. These potent and selective BET
      inhibitors represent a new class of compounds for the development of potential
      therapeutics against CRPC.

PMID- 29566489
TI  - Charged Surface Regulates the Molecular Interactions of Electrostatically
      Repulsive Peptides by Inducing Oriented Alignment.
AB  - Regulation of molecular orientation of charged dipeptides and involved
      interactions by electrostatic repulsion from like-charged surfaces were studied
      using all-atom molecular dynamics simulations. It was found that a charged
      surface can induce oriented alignment of like-charged peptides, and the oriented
      alignment leads to enhanced electrostatic repulsion between the peptide
      molecules. The findings are consistent with previous experimental results about
      the inhibition of charged protein aggregation using like-charged ion-exchange
      resin. Furthermore, the simulations provided molecular insights into this
      process, and demonstrated the distinct regulation effect of like-charged surfaces
      on the molecular interactions between peptides that possess an electric dipole
      structure. Both the charged surface and the electric dipole structure of peptides
      were confirmed to be crucial for the regulation. The research is expected to
      facilitate the rational design of surfaces or devices to regulate the behavior of
      amphoteric molecules such as proteins for both in vivo and in vitro applications,
      which would contribute to the regulation of protein-protein interactions and its
      application in life science and biotechnology.

PMID- 29566490
TI  - Moringa oleifera Seed Protein Adsorption to Silica: Effects of Water Hardness,
      Fractionation, and Fatty Acid Extraction.
AB  - Motivated by the proposed use of cationic protein-modified sand for water
      filtration in developing nations, this study concerns the adsorption of Moringa
      oleifera seed proteins to silica surfaces. These proteins were prepared in model
      waters of varying hardness and underwent different levels of fractionation,
      including fatty acid extraction and cation exchange chromatography. Adsorption
      isotherms were measured by ellipsometry, and the zeta potentials of the resulting
      protein-decorated surfaces were measured by the rotating disk streaming potential
      method. The results indicate that the presence of fatty acids has little effect
      on the M. oleifera cationic protein adsorption isotherm. Adsorption from the
      unfractionated extract was indistinguishable from that of the cationic protein
      isolates at low concentrations but yielded significantly greater extents of
      adsorption at high concentrations. Adsorption isotherms for samples prepared in
      model hard and soft fresh waters were indistinguishable from each other over the
      measured bulk solution concentration range, but adsorption from hard or soft
      water was more extensive than adsorption from deionized water at moderate protein
      concentrations. Streaming potential measurements showed that adsorption reversed
      the net sign of the zeta potential of silica from negative to positive for all
      protein fractions and water hardness conditions at protein bulk concentrations as
      low as 0.03 MUg/mL. This suggests that sands can be effectively modified with M.
      oleifera proteins using small amounts of seed extract under various local water
      hardness conditions. Finally, ellipsometry indicated that M. oleifera proteins
      adsorb irreversibly with respect to rinsing in these model fresh waters,
      suggesting that the modified sand would be stable on repeated use for water
      filtration. These studies may aid in the design of a simple, effective, and
      sustainable water purification device for developing nations.

PMID- 29566491
TI  - Resolving the Framework Position of Organic Structure-Directing Agents in
      Hierarchical Zeolites via Polarized Stimulated Raman Scattering.
AB  - The direct synthesis of hierarchically intergrown silicalite-1 can be achieved
      using a specific diquaternary ammonium agent. However, the location of these
      molecules in the zeolite framework, which is critical to understand the formation
      of the material, remains unclear. Where traditional characterization tools have
      previously failed, herein we use polarized stimulated Raman scattering (SRS)
      microscopy to resolve molecular organization inside few-micron-sized crystals.
      Through a combination of experiment and first-principles calculations, our
      investigation reveals the preferential location of the templating agent inside
      the linear pores of the MFI framework. Besides illustrating the attractiveness of
      SRS microscopy in the field of material science to study and spatially resolve
      local molecular distribution as well as orientation, these results can be
      exploited in the design of new templating agents for the preparation of
      hierarchical zeolites.

PMID- 29566493
TI  - A Glimpse into the Future of Sensing.

PMID- 29566495
TI  - Special Issue in Honor of Professor Susan Band Horwitz.

PMID- 29566494
TI  - Tailoring the Synthesis of LnF3 (Ln = La-Lu and Y) Nanocrystals via Mechanistic
      Study of the Coprecipitation Method.
AB  - Here, 15 LnF3 nanocrystals are synthesized using coprecipitation method with
      citrate stabilization to allow the fast, easy, and reproducible synthesis of
      several nanoscaled structures in water. General trends related to the behavior of
      LnF3 nanocrystals are highlighted due to their broad range of application in
      several fields (e.g., medical applications). The same nature for all Ln3+ cations
      is expected due to the internal role of f orbitals. However, we found that the
      use of different lanthanide elements is crucial in the final size, shape,
      assembly, and crystalline structure. In addition, the decrease of the cation size
      of the lanthanide series changes the behavior of these compounds, resulting in
      hexagonal, orthorhombic, and cubic crystalline structures. In addition, we are
      able to tune the cubic crystalline phase to pure orthorhombic by modifying the pH
      of the system using HBF4 instead of tetramethylammonium citrate. Via 11B NMR, we
      demonstrated the mechanism of HBF4 as fluorinating agent if an additional source
      of F- is not added during the synthesis. 1H NMR and IR techniques were performed
      to unravel the picture of the surface chemistry of the two representative metal
      cations (Y and La). Finally, HRTEM and SAED were performed to uncover the shape
      of the obtained nanocrystals and the preferential orientation of the assembled
      particles, giving crucial information on the involved mechanisms. This study
      reveals not only the dependence of the crystalline structure on the used metal
      and pH but also ability to achieve LnF3 assembled particles depending on the
      final shape and temperature.

PMID- 29566496
TI  - Perspective: Size selected clusters for catalysis and electrochemistry.
AB  - Size-selected clusters containing a handful of atoms may possess noble catalytic
      properties different from nano-sized or bulk catalysts. Size- and composition
      selected clusters can also serve as models of the catalytic active site, where an
      addition or removal of a single atom can have a dramatic effect on their activity
      and selectivity. In this perspective, we provide an overview of studies performed
      under both ultra-high vacuum and realistic reaction conditions aimed at the
      interrogation, characterization, and understanding of the performance of
      supported size-selected clusters in heterogeneous and electrochemical reactions,
      which address the effects of cluster size, cluster composition, cluster-support
      interactions, and reaction conditions, the key parameters for the understanding
      and control of catalyst functionality. Computational modeling based on density
      functional theory sampling of local minima and energy barriers or ab initio
      molecular dynamics simulations is an integral part of this research by providing
      fundamental understanding of the catalytic processes at the atomic level, as well
      as by predicting new materials compositions which can be validated in
      experiments. Finally, we discuss approaches which aim at the scale up of the
      production of well-defined clusters for use in real world applications.

PMID- 29566497
TI  - Efficient sampling of reversible cross-linking polymers: Self-assembly of single
      chain polymeric nanoparticles.
AB  - We present a new simulation technique to study systems of polymers functionalized
      by reactive sites that bind/unbind forming reversible linkages. Functionalized
      polymers feature self-assembly and responsive properties that are unmatched by
      the systems lacking selective interactions. The scales at which the functional
      properties of these materials emerge are difficult to model, especially in the
      reversible regime where such properties result from many binding/unbinding
      events. This difficulty is related to large entropic barriers associated with the
      formation of intra-molecular loops. In this work, we present a simulation scheme
      that sidesteps configurational costs by dedicated Monte Carlo moves capable of
      binding/unbinding reactive sites in a single step. Cross-linking reactions are
      implemented by trial moves that reconstruct chain sections attempting, at the
      same time, a dimerization reaction between pairs of reactive sites. The model is
      parametrized by the reaction equilibrium constant of the reactive species free in
      solution. This quantity can be obtained by means of experiments or
      atomistic/quantum simulations. We use the proposed methodology to study the self
      assembly of single-chain polymeric nanoparticles, starting from flexible
      precursors carrying regularly or randomly distributed reactive sites. We focus on
      understanding differences in the morphology of chain nanoparticles when linkages
      are reversible as compared to the well-studied case of irreversible reactions.
      Intriguingly, we find that the size of regularly functionalized chains, in good
      solvent conditions, is non-monotonous as a function of the degree of
      functionalization. We clarify how this result follows from excluded volume
      interactions and is peculiar of reversible linkages and regular
      functionalizations.

PMID- 29566498
TI  - Dense colloidal mixtures in an external sinusoidal potential.
AB  - Concentrated binary colloidal mixtures containing particles with a size ratio
      1:2.4 were exposed to a periodic potential that was realized using a light field,
      namely, two crossed laser beams creating a fringe pattern. The arrangement of the
      particles was recorded using optical microscopy and characterized in terms of the
      pair distribution function along the minima, the occupation probability
      perpendicular to the minima, the angular bond distribution, and the average
      potential energy per particle. The particle arrangement was investigated in
      dependence of the importance of particle-potential and particle-particle
      interactions by changing the potential amplitude and particle concentration,
      respectively. An increase in the potential amplitude leads to a stronger
      localization, especially of the large particles, but also results in an
      increasing fraction of small particles being located closer to the potential
      maxima, which also occurs upon increasing the particle density. Furthermore,
      increasing the potential amplitude induces a local demixing of the two particle
      species, whereas an increase in the total packing fraction favors a more
      homogeneous arrangement.

PMID- 29566499
TI  - Communication: Observation of ultra-slow relaxation in supercooled selenium and
      related glass-forming liquids.
AB  - The rheological behavior of supercooled Se, As10Se90, and As20Se80 liquids is
      studied in the linear regime as a function of frequency, extending over nearly 11
      orders of magnitude, using oscillatory parallel plate rheometry. While the
      viscoelastic response of the As20Se80 liquid is characterized by a single
      relaxation time scale, the Se and the As10Se90 liquids display two distinct
      relaxation processes, both of which are coupled to viscosity, although their time
      scales differ by nearly 3-5 orders of magnitude. The ultra-slow relaxation
      process appears to be related to the dynamics of -Se-Se-Se- chain segments in the
      structure of these liquids, with characteristic time scale and shear modulus that
      are dependent on the average chain length. The fast mode, on the other hand, is
      associated with the glassy modulus and is tentatively assigned to a Johari
      Goldstein beta-process. These results, when taken together, are consistent with
      the presence of a hierarchical free energy landscape that characterizes the
      dynamics of the fragile Se and As10Se90 liquids.

PMID- 29566500
TI  - Analytical energy gradients for explicitly correlated wave functions. II.
      Explicitly correlated coupled cluster singles and doubles with perturbative
      triples corrections: CCSD(T)-F12.
AB  - We present an implementation of analytical energy gradients for the explicitly
      correlated coupled cluster singles and doubles method with perturbative triples
      corrections [CCSD(T)-F12]. The accuracy of the CCSD(T)-F12 analytical gradient
      technique is demonstrated by computing equilibrium geometries for a set of closed
      shell molecules containing first- and second-row elements. Near basis-set limit
      equilibrium geometries are obtained with triple-zeta correlation consistent basis
      sets. Various approximations in the F12 treatment are compared, and the effects
      of these are found to be small.

PMID- 29566501
TI  - Morphology of size-selected Ptn clusters on CeO2(111).
AB  - Supported Pt catalysts and ceria are well known for their application in
      automotive exhaust catalysts. Size-selected Pt clusters supported on a CeO2(111)
      surface exhibit distinct physical and chemical properties. We investigated the
      morphology of the size-selected Ptn (n = 5-13) clusters on a CeO2(111) surface
      using scanning tunneling microscopy at room temperature. Ptn clusters prefer a
      two-dimensional morphology for n = 5 and a three-dimensional (3D) morphology for
      n >= 6. We further observed the preference for a 3D tri-layer structure when n >=
      10. For each cluster size, we quantitatively estimated the relative fraction of
      the clusters for each type of morphology. Size-dependent morphology of the Ptn
      clusters on the CeO2(111) surface was attributed to the Pt-Pt interaction in the
      cluster and the Pt-O interaction between the cluster and CeO2(111) surface. The
      results obtained herein provide a clear understanding of the size-dependent
      morphology of the Ptn clusters on a CeO2(111) surface.

PMID- 29566503
TI  - Molecular-dynamics study of propane-hydrate dissociation: Fluctuation-dissipation
      and non-equilibrium analysis.
AB  - Equilibrium and non-equilibrium molecular-dynamics (MD) simulations have been
      performed to investigate thermal-driven break-up of planar propane-hydrate
      interfaces in contact with liquid water over the 260-320 K range. Two types of
      hydrate-surface water-lattice molecular termination were adopted, at the hydrate
      edge with water, for comparison: a 001-direct surface cleavage and one with
      completed cages. Statistically significant differences in melting temperatures
      and initial break-up rates were observed between both interface types.
      Dissociation rates were observed to be strongly dependent on temperature, with
      higher rates at larger over-temperatures vis-a-vis melting. A simple coupled mass
      and heat transfer model, developed previously, was applied to fit the observed
      dissociation profiles, and this helps us to identify clearly two distinct hydrate
      decomposition regimes; following a highly temperature-dependent break-up phase, a
      second well-defined stage is essentially independent of temperature, in which the
      remaining nanoscale, de facto two-dimensional system's lattice framework is
      intrinsically unstable. Further equilibrium MD-analysis of the two-phase systems
      at their melting point, with consideration of the relaxation times gleaned from
      the auto-correlation functions of fluctuations in a number of enclathrated guest
      molecules, led to statistically significant differences between the two surface
      termination cases; a consistent correlation emerged in both cases between the
      underlying, non-equilibrium, thermal-driven dissociation rates sampled directly
      from melting with that from an equilibrium-MD fluctuation-dissipation approach.

PMID- 29566502
TI  - The role of entropic potential in voltage activation and K+ transport through Kv
      1.2 channels.
AB  - We analyze the entropic effects of inner pore geometry changes of Kv 1.2 channel
      during membrane depolarization and their implications for the rate of
      transmembrane transport of potassium ions. We base this on the idea that spatial
      confinements within the channel pore give rise to entropic barriers which can
      both effectively affect the stability of open macroconformation and influence
      channel's ability to conduct the potassium ions through the membrane. First, we
      calculate the differences in entropy between voltage-activated and resting states
      of the channel. As a template, we take a set of structures of channel pore in an
      open state at different membrane potentials generated in our previous research.
      The obtained results indicate that tendency to occupy open states at membrane
      depolarization is entropy facilitated. Second, we describe the differences in
      rates of K+ transport through the channel pore at different voltages based on the
      results of appropriate random walk simulations in entropic and electric
      potentials. The simulated single channel currents (I) suggest that the geometry
      changes during membrane depolarization are an important factor contributing to
      the observed flow of potassium ions through the channel. Nevertheless, the charge
      distribution within the channel pore (especially at the extracellular entrance)
      seems most prominent for the observed I/Imax relation at a qualitative level at
      analyzed voltages.

PMID- 29566504
TI  - Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular
      dynamics study.
AB  - Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids,
      which has shown promising applications in lowering Abeta peptide neurotoxicity in
      vitro by preventing aggregation of Abeta peptides and relieving accumulation of
      Abeta fibrils. Unfortunately, the underlying molecular mechanisms of how DHA
      interferes with the aggregation of Abeta peptides remain largely enigmatic.
      Herein, aggregation behaviors of amyloid-beta(Abeta)16-21 peptides (KLVFFA) with
      or without the presence of a DHA molecule were comparatively studied using
      extensive all-atom molecular dynamics simulations. We found that DHA could
      effectively suppress the aggregation of KLVFFA peptides by redirecting peptides
      to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made
      it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to
      form unstructured but stable complexes. These lower-ordered unstructured
      oligomers could eventually pass through energy barriers to form ordered beta
      sheet structures through large conformational fluctuations. This study depicts a
      microscopic picture for understanding the role and mechanism of DHA in inhibition
      of aggregation of Abeta peptides, which is generally believed as one of the
      important pathogenic mechanisms of Alzheimer's disease.

PMID- 29566505
TI  - Simplified approach to the mixed time-averaging semiclassical initial value
      representation for the calculation of dense vibrational spectra.
AB  - We present and test an approximate method for the semiclassical calculation of
      vibrational spectra. The approach is based on the mixed time-averaging
      semiclassical initial value representation method, which is simplified to a form
      that contains a filter to remove contributions from approximately harmonic
      environmental degrees of freedom. This filter comes at no additional numerical
      cost, and it has no negative effect on the accuracy of peaks from the anharmonic
      system of interest. The method is successfully tested for a model Hamiltonian and
      then applied to the study of the frequency shift of iodine in a krypton matrix.
      Using a hierarchic model with up to 108 normal modes included in the calculation,
      we show how the dynamical interaction between iodine and krypton yields results
      for the lowest excited iodine peaks that reproduce experimental findings to a
      high degree of accuracy.

PMID- 29566506
TI  - Note: Diffusion constant and solubility of helium in ULE glass at 23  degrees C.

PMID- 29566507
TI  - Photoinduced transport in an H64Q neuroglobin antidote for carbon monoxide
      poisoning.
AB  - Carbon monoxide (CO) is a leading cause of poisoning deaths worldwide, without
      available antidotal therapy. Recently, a potential treatment for CO poisoning was
      introduced, based on binding of CO by neuroglobin (Ngb) with a mutated distal
      histidine (H64Q). Here, we present an atomistic mechanism of CO trapping by H64Q
      Ngb revealed by nonadiabatic molecular dynamics. We focused on CO
      photodissociation and recombination of CO to wild type (WT) and H64Q Ngb. Our
      results demonstrate that the distribution of CO within the proteins differs
      substantially due to rearrangement of amino acids surrounding the distal heme
      pocket. This leads to the decrease of the distal pocket volume in H64Q Ngb in
      comparison to WT Ngb, trapping migrating CO molecules in the distal pocket. We
      show that the mutation implicates the shortening of the time scale of CO geminate
      recombination, making H64Q Ngb 2.7 times more frequent binder than WT Ngb.

PMID- 29566508
TI  - Weak polyelectrolyte complexation driven by associative charging.
AB  - Weak polyelectrolytes are relevant for a wide range of fields; in particular,
      they have been investigated as "smart" materials for chemical separations and
      drug delivery. The charges on weak polyelectrolytes are dynamic, causing polymer
      chains to adopt different equilibrium conformations even with relatively small
      changes to the surrounding environment. Currently, there exists no comprehensive
      picture of this behavior, particularly where polymer-polymer interactions have
      the potential to affect charging properties significantly. In this study, we
      elucidate the novel interplay between weak polyelectrolyte charging and
      complexation behavior through coupled molecular dynamics and Monte Carlo
      simulations. Specifically, we investigate a model of two equal-length and
      oppositely charging polymer chains in an implicit salt solution represented
      through Debye-Huckel interactions. The charging tendency of each chain, along
      with the salt concentration, is varied to determine the existence and extent of
      cooperativity in charging and complexation. Strong cooperation in the charging of
      these chains is observed at large Debye lengths, corresponding to low salt
      concentrations, while at lower Debye lengths (higher salt concentrations), the
      chains behave in apparent isolation. When the electrostatic coupling is long
      ranged, we find that a highly charged chain strongly promotes the charging of its
      partner chain, even if the environment is unfavorable for an isolated version of
      that partner chain. Evidence of this phenomenon is supported by a drop in the
      potential energy of the system, which does not occur at the lower Debye lengths
      where both potential energies and charge fractions converge for all partner chain
      charging tendencies. The discovery of this cooperation will be helpful in
      developing "smart" drug delivery mechanisms by allowing for better predictions
      for the dissociation point of delivery complexes.

PMID- 29566509
TI  - Theories of quantum dissipation and nonlinear coupling bath descriptors.
AB  - The quest of an exact and nonperturbative treatment of quantum dissipation in
      nonlinear coupling environments remains in general an intractable task. In this
      work, we address the key issues toward the solutions to the lowest nonlinear
      environment, a harmonic bath coupled both linearly and quadratically with an
      arbitrary system. To determine the bath coupling descriptors, we propose a
      physical mapping scheme, together with the prescription reference invariance
      requirement. We then adopt a recently developed dissipaton equation of motion
      theory [R. X. Xu et al., Chin. J. Chem. Phys. 30, 395 (2017)], with the
      underlying statistical quasi-particle ("dissipaton") algebra being extended to
      the quadratic bath coupling. We report the numerical results on a two-level
      system dynamics and absorption and emission line shapes.

PMID- 29566510
TI  - The coexistence temperature of hydrogen clathrates: A molecular dynamics study.
AB  - Extensive molecular dynamics simulations in the equilibrium isobaric-isothermal
      (NPT) ensemble were developed to determine the coexistence temperatures of the
      water hydrogen mixture using the direct coexistence method. The water molecules
      were modeled using the four-site TIP4P/Ice analytical potential, and the hydrogen
      molecules were described using a three-site potential. The simulations were
      performed at different pressures (p = 900, 1500, 3000, and 4000 bars). At each
      pressure, a series of simulations were developed at different temperatures (from
      230 to 270 K). Our results followed a line parallel to the experimental
      coexistence temperatures and underestimated these temperatures by approximately
      25 K in the investigated range. The final configurations could or could not
      contain a fluid phase depending on the pressure, in accordance with the phase
      diagram. In addition, we explored the dynamics of the H2 molecules through
      clathrate hydrate cages and observed different behaviors of the H2 molecules in
      the small cages and the large cages of the sII structure.

PMID- 29566511
TI  - Publisher's Note: "Electronic energy transfer through non-adiabatic vibrational
      electronic resonance. II. 1D spectra for a dimer" [J. Chem. Phys. 148, 084308
      (2018)].

PMID- 29566512
TI  - Vanishing mean volume velocity in isothermal isobaric diffusion of a binary fluid
      mixture.
AB  - It is shown that in isothermal isobaric diffusion of a binary fluid mixture, the
      mean volume velocity vanishes in the linear regime, independent of the equation
      of state. The partial specific volumes of the two components are uniform and
      constant in the process of mutual diffusion. The properties lead to a simple
      derivation of the de Groot-Mazur thermodynamic factor in the diffusion
      coefficient. The properties also imply that the diffusive volume flux defined by
      Brenner is proportional to the mass current density, and is therefore not a
      quantity of independent interest.

PMID- 29566513
TI  - Cavitation transition in the energy landscape: Distinct tensile yielding behavior
      in strongly and weakly attractive systems.
AB  - Particles with cohesive interactions display a tensile instability in the energy
      landscape at the Sastry density rhoS. The signature of this tensile limit is a
      minimum in the landscape equation of state, the pressure-density relationship of
      inherent structures sampled along a liquid isotherm. Our previous work [Y. E.
      Altabet, F. H. Stillinger, and P. G. Debenedetti, J. Chem. Phys. 145, 211905
      (2016)] revisited the phenomenology of Sastry behavior and found that the
      evolution of the landscape equation of state with system size for particles with
      interactions typical of molecular liquids indicates the presence of an athermal
      first-order phase transition between homogeneous and fractured inherent
      structures, the latter containing several large voids. Here, we study how this
      tensile limit manifests itself for different interparticle cohesive strengths and
      identify two distinct regimes. Particles with sufficiently strong cohesion
      display an athermal first-order phase transition, consistent with our prior
      characterization. Weak cohesion also displays a tensile instability. However, the
      landscape equation of state for this regime is independent of system size,
      suggesting the absence of a first-order phase transition. An analysis of the
      voids suggests that yielding in the energy landscape of weakly cohesive systems
      is associated with the emergence of a highly interconnected network of small
      voids. While strongly cohesive systems transition from exclusively homogeneous to
      exclusively fractured configurations at rhoS in the thermodynamic limit, this
      interconnected network develops gradually, starting at rhoS, even at infinite
      system size.

PMID- 29566514
TI  - An efficient zero-order description of the fine structure in the infrared
      reflection band of cubic ionic crystals and the phonon-polariton dispersion using
      Lorentz gauge.
AB  - The reflection of infrared light by ionic crystals with cubic symmetry such as
      lithium fluoride, LiF, is analyzed in terms of phonon-polaritons. In contrast to
      the conventional view on phonon-polaritons that uses the Coulomb gauge and
      assumes a purely local dielectric response of the material, we here develop an
      alternative description making use of the Lorentz gauge. This involves retarded
      interactions between charges, implying a non-local response of the material to
      electromagnetic radiation. The resulting new phonon-polariton dispersion relation
      features polaritons with negative group velocity in the frequency range in
      between the transverse (omegaT) and longitudinal frequency (omegaL). By contrast,
      the conventional description predicts, in zero order, the absence of any
      propagating polaritons in the frequency interval between omegaT and omegaL. The
      new dispersion relation provides an efficient, zero-order description of the fine
      structure within the reststrahlen band of LiF. The local minimum near the middle
      of the reflectance band is due to excitation of a phonon-polariton whose energy
      and momentum matches that of the incoming photon. The Lorentz gauge description
      can also describe off-normal reflection and accounts for the experimentally
      observed widening of the reflection band with increasing angle of incidence.

PMID- 29566515
TI  - Improved local lattice Monte Carlo simulation for charged systems.
AB  - Maggs and Rossetto [Phys. Rev. Lett. 88, 196402 (2002)] proposed a local lattice
      Monte Carlo algorithm for simulating charged systems based on Gauss's law, which
      scales with the particle number N as O(N). This method includes two degrees of
      freedom: the configuration of the mobile charged particles and the electric
      field. In this work, we consider two important issues in the implementation of
      the method, the acceptance rate of configurational change (particle move) and the
      ergodicity in the phase space sampled by the electric field. We propose a simple
      method to improve the acceptance rate of particle moves based on the
      superposition principle for electric field. Furthermore, we introduce an
      additional updating step for the field, named "open-circuit update," to ensure
      that the system is fully ergodic under periodic boundary conditions. We apply
      this improved local Monte Carlo simulation to an electrolyte solution confined
      between two low dielectric plates. The results show excellent agreement with
      previous theoretical work.

PMID- 29566516
TI  - High order discretization techniques for real-space ab initio simulations.
AB  - In this paper, we present discretization techniques to address numerical problems
      that arise when constructing ab initio approximations that use real-space
      computational grids. We present techniques to accommodate the singular nature of
      idealized nuclear and idealized electronic potentials, and we demonstrate the
      utility of using high order accurate grid based approximations to Poisson's
      equation in unbounded domains. To demonstrate the accuracy of these techniques,
      we present results for a Full Configuration Interaction computation of the
      dissociation of H2 using a computed, configuration dependent, orbital basis set.

PMID- 29566517
TI  - Variational nonadiabatic dynamics in the moving crude adiabatic representation:
      Further merging of nuclear dynamics and electronic structure.
AB  - A new methodology of simulating nonadiabatic dynamics using frozen-width Gaussian
      wavepackets within the moving crude adiabatic representation with the on-the-fly
      evaluation of electronic structure is presented. The main feature of the new
      approach is the elimination of any global or local model representation of
      electronic potential energy surfaces; instead, the electron-nuclear interaction
      is treated explicitly using the Gaussian integration. As a result, the new scheme
      does not introduce any uncontrolled approximations. The employed variational
      principle ensures the energy conservation and leaves the number of electronic and
      nuclear basis functions as the only parameter determining the accuracy. To assess
      performance of the approach, a model with two electronic and two nuclear spacial
      degrees of freedom containing conical intersections between potential energy
      surfaces has been considered. Dynamical features associated with nonadiabatic
      transitions and nontrivial geometric (or Berry) phases were successfully
      reproduced within a limited basis expansion.

PMID- 29566518
TI  - Gauge-origin independent formalism of two-component relativistic framework based
      on unitary transformation in nuclear magnetic shielding constant.
AB  - This article proposes a gauge-origin independent formalism of the nuclear
      magnetic shielding constant in the two-component relativistic framework based on
      the unitary transformation. The proposed scheme introduces the gauge factor and
      the unitary transformation into the atomic orbitals. The two-component
      relativistic equation is formulated by block-diagonalizing the Dirac Hamiltonian
      together with gauge factors. This formulation is available for arbitrary
      relativistic unitary transformations. Then, the infinite-order Douglas-Kroll-Hess
      (IODKH) transformation is applied to the present formulation. Next, the
      analytical derivatives of the IODKH Hamiltonian for the evaluation of the nuclear
      magnetic shielding constant are derived. Results obtained from the numerical
      assessments demonstrate that the present formulation removes the gauge-origin
      dependence completely. Furthermore, the formulation with the IODKH transformation
      gives results that are close to those in four-component and other two-component
      relativistic schemes.

PMID- 29566519
TI  - Structure and stability of charged colloid-nanoparticle mixtures.
AB  - Physical properties of colloidal materials can be modified by addition of
      nanoparticles. Within a model of like-charged mixtures of particles governed by
      effective electrostatic interactions, we explore the influence of charged
      nanoparticles on the structure and thermodynamic phase stability of charge
      stabilized colloidal suspensions. Focusing on salt-free mixtures of particles of
      high size and charge asymmetry, interacting via repulsive Yukawa effective pair
      potentials, we perform molecular dynamics simulations and compute radial
      distribution functions and static structure factors. Analysis of these structural
      properties indicates that increasing the charge and concentration of
      nanoparticles progressively weakens correlations between charged colloids. We
      show that addition of charged nanoparticles to a suspension of like-charged
      colloids can induce a colloidal crystal to melt and can facilitate aggregation of
      a fluid suspension due to attractive van der Waals interactions. We attribute the
      destabilizing influence of charged nanoparticles to enhanced screening of
      electrostatic interactions, which weakens repulsion between charged colloids.
      This interpretation is consistent with recent predictions of an effective
      interaction theory of charged colloid-nanoparticle mixtures.

PMID- 29566520
TI  - Comprehensive representation of the Lennard-Jones equation of state based on
      molecular dynamics simulation data.
AB  - The equation of state (EoS) of the Lennard-Jones fluid is calculated using a new
      set of molecular dynamics data which extends to higher temperature than in
      previous studies. The modified Benedict-Webb-Rubin (MBWR) equation, which goes up
      to ca. T ~ 6, is reparametrized with new simulation data. A new analytic form for
      the EoS, which breaks the fluid range into two regions with different analytic
      forms and goes up to ca. T ? 35, is also proposed. The accuracy of the new
      formulas is at least as good as the MBWR fit and goes to much higher temperature
      allowing it to now encompass the Amagat line. The fitted formula extends into the
      high temperature range where the system can be well represented by inverse power
      potential scaling, which means that our specification of the equation of state
      covers the entire (rho, T) plane. Accurate analytic fit formulas for the Boyle,
      Amagat, and inversion curves are presented. Parametrizations of the extrema loci
      of the isochoric, CV, and isobaric, CP, heat capacities are given. As found by
      others, a line maxima of CP terminates in the critical point region, and a line
      of minima of CP terminates on the freezing line. The line of maxima of CV
      terminates close to or at the critical point, and a line of minima of CV
      terminates to the right of the critical point. No evidence for a divergence in CV
      in the critical region is found.

PMID- 29566521
TI  - Observation of double-well potential of NaH C 1Sigma+ state: Deriving the
      dissociation energy of its ground state.
AB  - Vibrational levels (v = 6-42) of the NaH C 1Sigma+ state including the inner and
      outer wells and the near-dissociation region were observed by pulsed optical
      optical double resonance fluorescence depletion spectroscopy. The absolute
      vibrational quantum number is identified by comparing the vibrational energy
      difference of this experiment with the ab initio calculations. The outer well
      with v up to 34 is analyzed using the Dunham expansion and a Rydberg-Klein-Rees
      (RKR) potential energy curve is constructed. A hybrid double-well potential
      combined with the RKR potential, the ab initio calculation, and a long-range
      potential is able to describe the whole NaH C 1Sigma+ state including the higher
      vibrational levels (v = 35-42). The dissociation energy of the NaH C 1Sigma+
      state is determined to be De(C) = 6595.10 +/- 5 cm-1 and then the dissociation
      energy of the NaH ground state De(X) = 15 807.87 +/- 5 cm-1 can be derived.

PMID- 29566522
TI  - Nucleation study for an undercooled melt of intermetallic NiZr.
AB  - Electrostatic levitation is applied in order to undercool liquid glass forming
      NiZr significantly below its melting temperature. For NiZr large undercoolings
      are found to be highly reproducible with this experimental method. One single
      NiZr sample of high purity is undercooled 200 consecutive times which leads to a
      distribution function of undercooling temperatures. Within a statistical approach
      of classical nucleation theory, the undercooling distribution is analyzed
      yielding parameters, e.g., a pre-exponential factor of KV ~ 1035 m-3 s-1, which
      indicates homogeneous nucleation. This result is consistent with the
      crystallization behavior of NiZr at high undercooling and with the corresponding
      microstructural analysis. Since NiZr is a representative of the very common CrB
      structure type, with 132 isostructural phases existing, understanding its
      nucleation behavior adds important knowledge to the nucleation of binary alloys
      in general.

PMID- 29566523
TI  - Onsager's variational principle for the dynamics of a vesicle in a Poiseuille
      flow.
AB  - We propose a systematic formulation of the migration behaviors of a vesicle in a
      Poiseuille flow based on Onsager's variational principle, which can be used to
      determine the most stable steady state. Our model is described by a combination
      of the phase field theory for the vesicle and the hydrodynamics for the flow
      field. The dynamics is governed by the bending elastic energy and the dissipation
      functional, the latter being composed of viscous dissipation of the flow field,
      dissipation of the bending energy of the vesicle, and the friction between the
      vesicle and the flow field. We performed a series of simulations on 2-dimensional
      systems by changing the bending elasticity of the membrane and observed 3 types
      of steady states, i.e., those with slipper shape, bullet shape, and snaking
      motion, and a quasi-steady state with zig-zag motion. We show that the
      transitions among these steady states can be quantitatively explained by
      evaluating the dissipation functional, which is determined by the competition
      between the friction on the vesicle surface and the viscous dissipation in the
      bulk flow.

PMID- 29566524
TI  - Structure of the first order reduced density matrix in three electron systems: A
      generalized Pauli constraints assisted study.
AB  - We investigate the structure of the one-body reduced density matrix of three
      electron systems, i.e., doublet and quadruplet spin configurations, corresponding
      to the smallest interacting system with an open-shell ground state. To this end,
      we use configuration interaction (CI) expansions of the exact wave function in
      Slater determinants built from natural orbitals in a finite dimensional Hilbert
      space. With the exception of maximally polarized systems, the natural orbitals of
      spin eigenstates are generally spin dependent, i.e., the spatial parts of the up
      and down natural orbitals form two different sets. A measure to quantify this
      spin dependence is introduced and it is shown that it varies by several orders of
      magnitude depending on the system. We also study the ordering issue of the spin
      dependent occupation numbers which has practical implications in reduced density
      matrix functional theory minimization schemes, when generalized Pauli constraints
      (GPCs) are imposed and in the form of the CI expansion in terms of the natural
      orbitals. Finally, we discuss the aforementioned CI expansion when there are GPCs
      that are almost "pinned."

PMID- 29566525
TI  - Including diverging electrostatic potential in 3D-RISM theory: The charged wall
      case.
AB  - Although three-dimensional site-site molecular integral equations of liquids are
      a powerful tool of the modern theoretical chemistry, their applications to the
      problem of characterizing the electrical double layer originating at the solid
      liquid interface with a macroscopic substrate are severely limited by the fact
      that an infinitely extended charged plane generates a divergent electrostatic
      potential. Such potentials cannot be treated within the standard 3D-Reference
      Interaction Site Model equation solution framework since it leads to functions
      that are not Fourier transformable. In this paper, we apply a renormalization
      procedure to overcome this obstacle. We then check the validity and numerical
      accuracy of the proposed computational scheme on the prototypical gold (111)
      surface in contact with water/alkali chloride solution. We observe that despite
      the proposed method requires, to achieve converged charge densities, a higher
      spatial resolution than that suited to the estimation of biomolecular solvation
      with either 3D-RISM or continuum electrostatics approaches, it still is
      computationally efficient. Introducing the electrostatic potential of an infinite
      wall, which is periodic in 2 dimensions, we avoid edge effects, permit a robust
      integration of Poisson's equation, and obtain the 3D electrostatic potential
      profile for the first time in such calculations. We show that the potential
      within the electrical double layer presents oscillations which are not grasped by
      the Debye-Huckel and Gouy-Chapman theories. This electrostatic potential deviates
      from its average of up to 1-2 V at small distances from the substrate along the
      lateral directions. Applications of this theoretical development are relevant,
      for example, for liquid scanning tunneling microscopy imaging.

PMID- 29566526
TI  - Double photoionization of propylene oxide: A coincidence study of the ejection of
      a pair of valence-shell electrons.
AB  - Propylene oxide, a favorite target of experimental and theoretical studies of
      circular dichroism, was recently discovered in interstellar space, further
      amplifying the attention to its role in the current debate on protobiological
      homochirality. In the present work, a photoelectron-photoion-photoion coincidence
      technique, using an ion-imaging detector and tunable synchrotron radiation in the
      18.0-37.0 eV energy range, permits us (i) to observe six double ionization
      fragmentation channels, their relative yields being accounted for about two
      thirds by the couple (C2H4+, CH2O+) and one-fifth by (C2H3+, CH3O+); (ii) to
      measure thresholds for their openings as a function of photon energy; and (iii)
      to unravel a pronounced bimodality for a kinetic-energy-released distribution,
      fingerprint of competitive non-adiabatic mechanisms.

PMID- 29566527
TI  - Multiplexed direct-frequency-comb Vernier spectroscopy of carbon dioxide 2nu1 +
      nu3 ro-vibrational combination band.
AB  - We investigated a set of nineteen 12C16O2 transitions of the 2nu1 + nu3 ro
      vibrational band in the spectral region from 5064 to 5126 cm-1 at different
      pressures, using frequency-comb Vernier spectroscopy. Our spectrometer enabled
      the systematic acquisition of molecular absorption profiles with high precision.
      Spectroscopic parameters, namely, transition frequency, linestrength, and self
      pressure broadening coefficient, have been accurately determined by using a
      global fit procedure. These data are in agreement with theoretical values
      contained in HITRAN2016 database [I. E. Gordon et al., J. Quant. Spectrosc.
      Radiat. Transfer 203, 3-69 (2017)] at the same precision level. A moderate
      improvement of the line intensity determinations, by a factor 1.5 in the best
      case [P(10) transition at 5091.6 cm-1], should be noticed, projecting direct-comb
      Vernier-spectroscopy as an adequate tool for spectral intensity calibration.

PMID- 29566528
TI  - Fullerene/layered antiferromagnetic reconstructed spinterface: Subsurface layer
      dominates molecular orbitals' spin-split and large induced magnetic moment.
AB  - The interfaces between organic molecules and magnetic metals have gained
      increasing interest for both fundamental reasons and applications. Among them,
      the C60/layered antiferromagnetic (AFM) interfaces have been studied only for C60
      bonded to the outermost ferromagnetic layer [S. L. Kawahara et al., Nano Lett.
      12, 4558 (2012) and D. Li et al., Phys. Rev. B 93, 085425 (2016)]. Here, via
      density functional theory calculations combined with evidence from the
      literature, we demonstrate that C60 adsorption can reconstruct the layered-AFM
      Cr(001) surface at elevated annealing temperatures so that C60 bonds to both the
      outermost and the subsurface Cr layers in opposite spin directions. Surface
      reconstruction drastically changes the adsorbed molecule spintronic properties:
      (1) the spin-split p-d hybridization involves multi-orbitals of C60 and top two
      layers of Cr with opposite spin-polarization, (2) the subsurface Cr atom
      dominates the C60 electronic properties, and (3) the reconstruction induces a
      large magnetic moment of 0.58 MUB in C60 as a synergistic effect of the top two
      Cr layers. The induced magnetic moment in C60 can be explained by the magnetic
      direct-exchange mechanism, which can be generalized to other C60/magnetic metal
      systems. Understanding these complex hybridization behaviors is a crucial step
      for molecular spintronic applications.

PMID- 29566529
TI  - Heterogeneous nucleation of a droplet pinned at a chemically inhomogeneous
      substrate: A simulation study of the two-dimensional Ising case.
AB  - Heterogeneous nucleation is studied by Monte Carlo simulations and
      phenomenological theory, using the two-dimensional lattice gas model with
      suitable boundary fields. A chemical inhomogeneity of length b at one boundary
      favors the liquid phase, while elsewhere the vapor is favored. Switching on the
      bulk field Hb favoring the liquid, nucleation and growth of the liquid phase
      starting from the region of the chemical inhomogeneity are analyzed. Three
      regimes occur: for small fields, Hb<Hbcrit, the critical droplet radius is so
      large that a critical droplet having the contact angle thetac required by Young's
      equation in the region of the chemical inhomogeneity does not yet "fit" there
      since the baseline length of the circle-cut sphere droplet would exceed b. For
      Hbcrit<Hb<Hb*, such droplets fit inside the inhomogeneity and are indeed found in
      simulations with large enough observation times, but these droplets remain pinned
      to the chemical inhomogeneity when their baseline has grown to the length b.
      Assuming that these pinned droplets have a circle cut shape and effective contact
      angles thetaeff in the regime thetac < thetaeff < pi/2, the density excess due to
      these droplets can be predicted and is found to be in reasonable agreement with
      the simulation results. On general grounds, one can predict that the effective
      contact angle thetaeff and the excess density of the droplets, scaled by b, are
      functions of the product bHb but do not depend on both variables separately.
      Since the free energy barrier for the "depinning" of the droplet (i.e., growth of
      thetaeff to pi - thetac) vanishes when thetaeff approaches pi/2, in practice only
      angles thetaeff up to about thetaeffmax?70 degrees  were observed. For larger
      fields (Hb>Hb*), the droplets nucleated at the chemical inhomogeneity grow to the
      full system size. While the relaxation time for the growth scales as tauG?Hb-1,
      the nucleation time tauN scales as lntauN?Hb-1. However, the prefactor in the
      latter relation, as evaluated for our simulations results, is not in accord with
      an extension of the Volmer-Turnbull theory to two-dimensions, when the
      theoretical contact angle thetac is used.

PMID- 29566530
TI  - Three-beam double stimulated Raman scatterings: Cascading configuration.
AB  - Two-beam stimulated Raman scattering (SRS) has been used in diverse label-free
      spectroscopy and imaging applications of live cells, biological tissues, and
      functional materials. Recently, we developed a theoretical framework for the
      three-beam double SRS processes that involve pump, Stokes, and depletion beams,
      where the pump-Stokes and pump-depletion SRS processes compete with each other.
      It was shown that the net Stokes gain signal can be suppressed by increasing the
      depletion beam intensity. The theoretical prediction has been experimentally
      confirmed recently. In the previous scheme for a selective suppression of one SRS
      by making it compete with another SRS, the two SRS processes occur in a parallel
      manner. However, there is another possibility of three-beam double SRS scheme
      that can be of use to suppress either Raman gain of the Stokes beam or Raman loss
      of the pump beam by depleting the Stokes photons with yet another SRS process
      induced by the pair of Stokes and another (second) Stokes beam. This three-beam
      double SRS process resembles a cascading energy transfer process from the pump
      beam to the first Stokes beam (SRS-1) and subsequently from the first Stokes beam
      to the second Stokes beam (SRS-2). Here, the two stimulated Raman gain-loss
      processes are associated with two different Raman-active vibrational modes of
      solute molecule. In the present theory, both the radiation and the molecules are
      treated quantum mechanically. We then show that the cascading-type three-beam
      double SRS can be described by coupled differential equations for the photon
      numbers of the pump and Stokes beams. From the approximate solutions as well as
      exact numerical calculation results for the coupled differential equations, a
      possibility of efficiently suppressing the stimulated Raman loss of the pump beam
      by increasing the second Stokes beam intensity is shown and discussed. To further
      prove a potential use of this scheme for developing a super-resolution SRS
      microscopy, we present a theoretical expression and numerical simulation results
      for the full-width-at-half-maximum of SRS imaging point spread function, assuming
      that the pump and Stokes beam profiles are Gaussian and the second Stokes beam
      has a doughnut-shaped spatial profile. It is clear that the spatial resolution
      with the present 3-beam cascading SRS method can be enhanced well beyond the
      diffraction limit. We anticipate that the present work will provide a theoretical
      framework for a super-resolution stimulated Raman scattering microscopy that is
      currently under investigation.

PMID- 29566531
TI  - Collective excitations and ultrafast dipolar solvation dynamics in water-ethanol
      binary mixture.
AB  - In order to understand the intermolecular vibrational spectrum and the collective
      excitations of water-ethanol binary mixture, we investigate the density of states
      and the power spectrum using computer simulations aided by theory. We investigate
      in particular the spectra at intermediate to low frequencies (a few hundreds to
      few tens of cm-1) by calculating (i) the density of states from quenched normal
      modes, (ii) the power spectrum from velocity time correlation function, and (iii)
      the far infrared and dielectric spectra (that is, the Cole-Cole plot) from the
      total dipole moment time correlation function. The different spectra are in broad
      agreement with each other and at the same time reveal unique characteristics of
      the water-ethanol mixture. Inverse participation ratio reveals several
      interesting features. Libration of pure ethanol is more localized than that of
      pure water. With increasing ethanol content, we observe localization of the
      collective libration mode as well as of the hindered translational and rotational
      mode. An interesting mixing between the libration of water and ethanol is
      observed. Solvation dynamics of tryptophan measured by equilibrium energy
      fluctuation time correlation function show surprisingly strong non-linear
      dependence on composition that can be tested against experiments.

PMID- 29566532
TI  - Reaction enthalpy from the binding of multivalent cations to anionic
      polyelectrolytes in dilute solutions.
AB  - Dilute solutions of sodium poly(styrene sulfonate) (NaPSS) in the presence of
      Al3+, Ca2+, and Ba2+ were analysed by means of isothermal titration calorimetry
      (ITC) in order to investigate the heat effect of bond formation between those
      cations and the anionic SO3- residues of NaPSS. The selection of the cations was
      guided by the solution behavior of the corresponding PSS salts from a preceding
      study [M. Hansch et al., J. Chem. Phys. 148(1), 014901 (2018)], where bonds
      between Ba2+ and anionic PSS showed an increasing solubility with decreasing
      temperature and Al3+ exhibited the inverse trend. Unlike to Al3+ and Ba2+, Ca2+
      is expected to behave as a purely electrostatically interacting bivalent cation
      and was thus included in the present study. Results from ITC satisfactorily
      succeeded to explain the temperature-dependent solution behavior of the salts
      with Al3+ and Ba2+ and confirmed the non-specific behavior of Ca2+. Additional
      ITC experiments with salts of Ca2+ and Ba2+ and sodium poly(acrylate)
      complemented the results on PSS by data from a chemically different polyanion.
      Availability of these joint sets of polyanion-cation combinations not only offers
      the chance to identify common features and subtle differences in the solution
      behavior of polyelectrolytes in the presence of multi-valent cations but also
      points to a new class of responsive materials.

PMID- 29566533
TI  - Penning ionization widths by Fano-algebraic diagrammatic construction method.
AB  - We present an ab initio theory and computational method for Penning ionization
      widths. Our method is based on the Fano theory of resonances, algebraic
      diagrammatic construction (ADC) scheme for many-electron systems, and Stieltjes
      imaging procedure. It includes an extension of the Fano-ADC scheme [V. Averbukh
      and L. S. Cederbaum, J. Chem. Phys. 123, 204107 (2005)] to triplet excited
      states. Penning ionization widths of various He*-H2 states are calculated as a
      function of the distance R between He* and H2. We analyze the asymptotic (large
      R) dependences of the Penning widths in the region where the well-established
      electron transfer mechanism of the decay is suppressed by the multipole- and/or
      spin-forbidden energy transfer. The R-12 and R-8 power laws are derived for the
      asymptotes of the Penning widths of the singlet and triplet excited states of
      He*(1s2s1,3S), respectively. We show that the electron transfer mechanism
      dominates Penning ionization of He*(1s2s 3S)-H2 up until the He*-H2 separation is
      large enough for the radiative decay of He* to become the dominant channel. The
      same mechanism also dominates the ionization of He*(1s2s 1S)-H2 when R < 5 A. We
      estimate that the regime of energy transfer in the He*-H2 Penning ionization
      cannot be reached by approaching zero collisional temperature. However, the
      multipole-forbidden energy transfer mechanism can become important for Penning
      ionization in doped helium droplets.

PMID- 29566534
TI  - Updates in Stroke Care.

PMID- 29566535
TI  - "You Want Your Guests to Be Happy in This Business": Hoteliers' Decisions to
      Adopt Voluntary Smoke-Free Guest-Room Policies.
AB  - PURPOSE:: To explore why some hotels have implemented 100% smoke-free policies
      voluntarily, the perceived consequences of doing so, and media responses.
      DESIGN:: Qualitative study of hotel management and quantitative content analysis
      of media coverage of smoke-free hotels. SETTING:: Hotels and media based in the
      United States. PARTICIPANTS:: Eleven representatives of 5 independent and 4 chain
      hotels. Other data included 265 news items about smoke-free hotels. METHOD:: We
      conducted 30-minute semi-structured interviews with hotel representatives and
      analyzed the data using qualitative content analysis. We also searched 3 online
      news databases for news items about hotels in our study, and collaboratively
      coded retrieved items; we analyzed the content and slant of news items. RESULTS::
      Business considerations, including guest requests, competitor action, and cost
      savings, were the primary motivations for implementing 100% smoke-free guest-room
      policies. Health concerns played a minimal role. Hotels received positive
      feedback from customers and employees. Media coverage was favorable, emphasizing
      positive aspects of going smoke-free; the overall slant of news items was
      positive or neutral. However, few hotels marketed the change. CONCLUSIONS:: Since
      hotel customers and employees are likely to experience long periods of smoke
      exposure and smoke-free hotels appear to be so well received, it may be timely to
      pursue policies making all hotels smoke-free.

PMID- 29566536
TI  - Trends in Cigarette Advertising, Price-Reducing Promotions, and Policy Compliance
      in New York State Licensed Tobacco Retailers, 2004 to 2015.
AB  - PURPOSE:: To describe the presence of licensed tobacco retailers (LTRs),
      cigarette advertisements, price-reducing promotions, and compliance with tobacco
      control policies in New York State from 2004 to 2015 and to discuss implications
      and lessons learned from 11 years of experience conducting LTR surveys. DESIGN::
      Annual surveys of tobacco advertising from cross-sectional, stratified random
      samples of LTRs in New York State from 2004 to 2015 were conducted by
      professional data collectors. Data for 2013 were unavailable as the survey was
      not fielded in that year. SETTING:: New York State. PARTICIPANTS:: Licensed
      tobacco retailers, which are stores licensed to sell tobacco in the state of New
      York. Between 3.6% (n = 800) and 19.7% (n = 3945) of all LTRs were sampled
      annually. MEASURES:: The presence and number of cigarette advertisements and the
      presence of price-reducing promotions, required age-of-sale signage, and self
      service tobacco displays were documented. ANALYSIS:: We tested for significant
      differences between 2014 and 2015 and significant trends overall and by outlet
      type. We used logistic regression for binary outcomes and Poisson regression for
      count variables. RESULTS:: The number of LTRs in New York State decreased 22.9%
      from 2004 (n = 25 740) to 2015 (n = 19 855). The prevalence and number of
      cigarette advertisements and the prevalence of cigarette price-reducing
      promotions decreased significantly over time. Compliance with posting required
      age-of-sale signs increased significantly from 2004 to 2015 and from 2014 to
      2015. Compliance with the ban on self-service tobacco displays was consistently
      near 100%. CONCLUSION:: The tobacco retail environment in New York State improved
      substantially from 2004 to 2015. The implications of these findings for youth and
      adult smoking and the associated social costs are unknown; however, decreases in
      pro-tobacco marketing, decreases in the number of LTRs, and improvements in
      compliance are likely to have positive impacts on youth and adult smoking
      outcomes, such as reduced initiation and increased cessation, given previous
      research findings.

PMID- 29566537
TI  - Treatment with platelet-rich plasma of surgically related dormant corneal ulcers.
AB  - PURPOSE: To assess the effectiveness of autologous platelet-rich plasma for the
      treatment of dormant corneal ulcers secondary to corneal surgery and unresponsive
      to conventional treatment. SETTING: VISSUM, Ophthalmology Institute of Alicante,
      Alicante, Spain. DESIGN: Prospective nonrandomized, observational consecutive
      study. METHODS: A total of 44 eyes of 28 patients with dormant corneal ulcers
      secondary to corneal surgery were included in a prospective study and treated
      with autologous platelet-rich plasma during 6 weeks. Wilcoxon signed-rank test
      was used to compare the effect of the treatment. RESULTS: In all, 28 patients
      (65.1%) improved their visual acuity at least one line in Snellen chart, 26
      (59.09%) had a decrease in the size of the ulcer or even a total closure, and 40
      (90.9%) experienced an improvement in their symptoms. The results are also
      provided for the four groups of patients (keratoplasty, refractive surgery, cross
      linking, and chronic postsurgical corneal edema). CONCLUSION: Platelet-rich
      plasma eye drops shows to be a good option for the treatment of dormant corneal
      ulcers secondary to corneal surgery.

PMID- 29566538
TI  - Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line
      antiretroviral therapy failures in South Africa.
AB  - Background Rilpivirine (TMC278LA) is a promising drug for pre-exposure
      prophylaxis of HIV-1 because of its sub-nanomolar potency and long-acting
      formulation; however, increasing transmission of non-nucleoside reverse
      transcriptase inhibitor-resistant HIV-1 with potential cross-resistance to
      rilpivirine could reduce its preventive efficacy. This study investigated
      rilpivirine cross-resistance among recombinant subtype C HIV-1 derived from 100
      individuals failing on first-line non-nucleoside reverse transcriptase inhibitor
      containing antiretroviral therapy in South Africa whose samples were sent for
      routine HIV-1 drug resistance testing to Lancet Laboratories (Johannesburg, South
      Africa). Methods Plasma samples were selected from individuals with HIV-1 RNA >
      10,000 copies/ml and >=1 non-nucleoside reverse transcriptase inhibitor
      resistance mutation in reverse transcriptase. Recombinant HIV-1LAI-containing
      bulk-cloned full-length reverse transcriptase sequences from plasma were assayed
      for susceptibility to nevirapine (NVP), efavirenz (EFV) and rilpivirine in TZM-bl
      cells. Fold-change (FC) decreases in drug susceptibility were calculated against
      a mean IC50 from 12 subtype C HIV-1 samples from treatment-naive individuals in
      South Africa. Cross-resistance was evaluated based on biological cutoffs
      established for rilpivirine (2.5-FC) and the effect of mutation combinations on
      rilpivirine phenotype. Results Of the 100 samples from individuals on failing
      antiretroviral therapy, 69 had 2.5- to 75-fold decreased susceptibility to
      rilpivirine and 11 had >75-fold resistance. Rilpivirine resistance was strongly
      associated with K103N especially in combination with other rilpivirine-associated
      mutations. Conclusion The frequently observed cross-resistance of HIV-1 suggests
      that the preventive efficacy of TMC278LA pre-exposure prophylaxis could be
      compromised by transmission of HIV-1 from individuals with failure of first-line
      non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy.

PMID- 29566540
TI  - Molecular studies of CGRP and the CGRP family of peptides in the central nervous
      system.
AB  - Background Calcitonin gene-related peptide is an important target for migraine
      and other painful neurovascular conditions. Understanding the normal biological
      functions of calcitonin gene-related peptide is critical to understand the
      mechanisms of calcitonin gene-related peptide-blocking therapies as well as
      engineering improvements to these medications. Calcitonin gene-related peptide is
      closely related to other peptides in the calcitonin gene-related peptide family
      of peptides, including amylin. Relatedness in peptide sequence and in receptor
      biology makes it difficult to tease apart the contributions that each peptide and
      receptor makes to physiological processes and to disorders. Summary The focus of
      this review is the expression of calcitonin gene-related peptide, related
      peptides and their receptors in the central nervous system. Calcitonin gene
      related peptide is expressed throughout the nervous system, whereas amylin and
      adrenomedullin have only limited expression at discrete sites in the brain. The
      components of two receptors that respond to calcitonin gene-related peptide, the
      calcitonin gene-related peptide receptor (calcitonin receptor-like receptor with
      receptor activity-modifying protein 1) and the AMY1 receptor (calcitonin receptor
      with receptor activity-modifying protein 1), are expressed throughout the nervous
      system. Understanding expression of the peptides and their receptors lays the
      foundation for more deeply understanding their physiology, pathophysiology and
      therapeutic use.

PMID- 29566539
TI  - Ultrastructural effects of silicone oil on the clear crystalline lens of the
      human eye.
AB  - PURPOSE: To evaluate light and electron microscopic changes of the anterior
      capsule and its epithelium after clear lens extraction of vitrectomized myopic
      eyes with silicone oil tamponade. METHODS: This prospective, controlled, non
      randomized, interventional study included 20 anterior lens capsular specimens
      that were excised during combined clear lens extraction and silicone oil removal
      from previously vitrectomized highly myopic patients with silicone oil tamponade
      for previous retinal detachment surgeries. The specimens were examined via light
      microscopy and electron microscopy and compared with 20 anterior capsule
      specimens removed during clear lens extraction of non-vitrectomized highly myopic
      eyes. RESULTS: Light microscopic examination of clear lens anterior capsule
      specimens of vitrectomized myopic eyes filled with silicone oil showed relatively
      more flat cells with irregular outline of lens' epithelial cells with wide
      intercellular spaces, deeply stained nuclei, and multiple intracytoplasmic
      vacuoles. Scanning electron microscopy revealed collagenous surfaces filled with
      multiple pits, depressions, and abnormal deposits. Transmission electron
      microscopy revealed lens epithelial cells with apoptotic changes, many
      cytoplasmic vacuoles, and filopodia-like protrusions between lens epithelial
      cells and the capsule. Epithelial proliferation and multilayering were also
      observed. CONCLUSION: silicone oil may play a role in the development of
      apoptotic and histopathological changes in clear lens epithelial cells. Clarity
      of the lens at the time of silicone oil removal does not indicate an absence of
      cataractous changes. We found justification of combined clear lens extraction and
      silicone oil removal or combined phacovitrectomy when silicone oil injection is
      planned, but further long-term studies with larger patient groups are required.

PMID- 29566541
TI  - Advance care planning for people with dementia: Ordinary everyday conversations.
AB  - Advance care planning for people with dementia has become a focus of dementia
      care policies in developed countries. In New Zealand, the framework for dementia
      care relies on the person with dementia having a level of competence to enable
      them to participate in the planning process. For people with dementia, it may be
      too late to initiate these discussions in terms of decision-making capacity.
      Consequently, decisions about end-of-life care for people with dementia are
      typically made by a family member who acts as a surrogate decision maker on
      behalf of the person with dementia. An exploratory qualitative study of 23 people
      who had been carers or provided support for a family member with dementia who had
      died within five years of the interview was undertaken. The overarching theme,
      'ordinary everyday conversations', describes how informal conversations and
      discussions within the family relating to preferences at the end of life had been
      embedded in interactions within the families over years. Sub-themes revealed
      three important components enabling adherence to the prior wishes of the person
      with dementia through these conversations: knowing the person and belief in
      'doing the right thing'; the importance of Wills and Enduring Power of Attorney;
      and negotiating unexpected encounters. There is potential for families to be well
      prepared for the time when they may need to make decisions for the person with
      dementia based on ordinary everyday conversation that take place within families
      and throughout life. This study also suggests that more innovative approaches to
      making a Will may provide an important vehicle for expressing advanced care
      wishes.

PMID- 29566542
TI  - Comparative evaluation of Scheimpflug tomography parameters between thin non
      keratoconic, subclinical keratoconic, and mild keratoconic corneas.
AB  - PURPOSE: To evaluate and compare the topographic and topometric parameters,
      thickness profile data, and data from enhanced elevation maps of thin non
      keratoconic, subclinical keratoconic, and mild keratoconic corneas with the
      Pentacam Scheimpflug corneal tomography and to study the usefulness of different
      parameters to differentiate keratoconus from topographically normal thin corneas.
      METHODS: The study included 30 eyes with subclinical keratoconus, 30 eyes with
      mild-stage keratoconus, and 54 healthy eyes with minimal pachymetry <=500 um,
      with a mean age of 21.19 +/- 2.97, 21.75 +/- 1.93, and 21.5 +/- 2.95 years,
      respectively. The area under the receiver operating characteristic curves was
      used to analyze the diagnostic significance of the Pentacam parameters. RESULTS:
      The anterior and posterior corneal elevations, pachymetric progression, the
      percentage of thickness increase measurements, overall D value, and topometric
      indices were statistically significantly higher in subclinical and mild
      keratoconic corneas than in normal eyes with thin cornea (p < 0.05). All these
      parameters had sufficient strength (area under the receiver operating
      characteristic curves >0.90) to differentiate clinical keratoconus. Posterior
      elevation showed the excellent area under the receiver operating characteristic
      curves with 100% sensitivity and 100% specificity for this purpose. However,
      among all parameters studied, the anterior elevation (0.935) showed the excellent
      area under the receiver operating characteristic curves to differentiate
      subclinical keratoconus, followed by posterior elevation (0.897), index of height
      decentration (0.887), and D value (0.882). CONCLUSION: The parameters derived
      from the Scheimpflug device, such as corneal elevations and overall D value, can
      effectively differentiate subclinical and clinical keratoconus from non
      keratoconic thin cornea eyes. However, the specificity levels of these parameters
      were relatively limited in the diagnosis of subclinical keratoconus.

PMID- 29566543
TI  - Beetroot-based gel supplementation improves handgrip strength and forearm muscle
      O2 saturation but not exercise tolerance and blood volume in jiu-jitsu athletes.
AB  - The ergogenic effect of beetroot on the exercise performance of trained cyclists,
      runners, kayakers, and swimmers has been demonstrated. However, whether or not
      beetroot supplementation presents a beneficial effect on the exercise performance
      of jiu-jitsu athletes remains inconclusive. Therefore, the present study assessed
      the effect of beetroot-based gel (BG) supplementation on maximal voluntary
      contraction (MVC), exercise time until fatigue (ETF), muscle O2 saturation
      (SmO2), blood volume (tHb), and plasma nitrate and lactate in response to
      handgrip isotonic exercise (HIE) in jiu-jitsu athletes. In a randomized,
      crossover, double-blind design, 12 jiu-jitsu athletes performed 3 sets of HIE at
      40% of the MVC until fatigue after 8 days (the eighth dose was offered 120 min
      previous exercise) of BG supplementation or a nitrate-depleted gel (PLA), and
      forearm SmO2 and tHb were continuously monitored by using near-infrared
      spectroscopy. Blood samples were taken before, immediately after exercise, and 20
      min after exercise recovery in the PLA and BG conditions. MVC was evaluated at
      baseline and 20 min after HIE. There was a significant reduction in DeltaMVC
      decline after HIE in the BG condition. Forearm SmO2 during exercise recovery was
      significantly greater only after BG supplementation. No significant difference in
      ETF and tHb were observed between both BG and PLA in response to HIE. Plasma
      nitrate increased only after BG, whereas the exercise-induced increase in plasma
      lactate was significantly lower in BG when compared with PLA. In conclusion, BG
      supplementation may be a good nutritional strategy to improve forearm SmO2 and
      prevent force decline in response to exercise in jiu-jitsu athletes.

PMID- 29566544
TI  - The effects of priming exercise on the VO2 slow component and the time-course of
      muscle fatigue during very-heavy-intensity exercise in humans.
AB  - We hypothesized that prior exercise would attenuate the muscle fatigue
      accompanied by oxygen uptake slow-component (VO2SC) behavior during a subsequent
      very-heavy (VH)-intensity cycling exercise. Thirteen healthy male subjects
      performed tests to determine the critical power (CP) and the fixed amount of work
      above CP ([Formula: see text]) and performed 6 square-wave bouts until 3 or 8
      min, each at a work rate set to deplete 70% [Formula: see text] in 8 min, with a
      maximal isokinetic effort before and after the conditions without (VHCON) and
      with prior exercise (VHEXP), to measure the cycling peak torque decrement. The
      VO2SC magnitude at 3 min (VHCON = 0.280 +/- 0.234, VHEXP = 0.116 +/- 0.109 L.min
      1; p = 0.04) and the VO2SC trajectory were significantly lower for VHEXP (VHCON =
      0.108 +/- 0.042, VHEXP = 0.063 +/- 0.031 L.min-2; p < 0.01), leading to a VO2SC
      magnitude at the eighth minute that was significantly lower than VHCON (VHCON =
      0.626 +/- 0.296 L.min-1, VHEXP = 0.337 +/- 0.179; p < 0.01). Conversely, peak
      torque progressively decreased from pre-exercise to 3 min (Deltatorque = 21.5 +/-
      7.7 vs. 19.6 +/- 9.2 Nm) and to 8 min (Deltatorque = 29.4 +/- 15.8 vs. 27.5 +/-
      12.0 Nm) at VHCON and VHEXP, respectively, without significant differences
      between conditions. Regardless of the condition, there was a significant
      relationship between Deltatorque and the VO2SC (R2: VHCON = 0.23, VHEXP = 0.25; p
      = 0.01). Considering that "priming" effects on the VO2SC were not accompanied by
      the muscle force behavior, these findings do not support the hypothesis of a
      "causal" relationship between the time-course of muscle fatigue and VO2SC.

PMID- 29566545
TI  - Effect of duration and severity of migraine on retinal nerve fiber layer,
      ganglion cell layer, and choroidal thickness.
AB  - PURPOSE:: To investigate the factors in migraine that have the highest
      significance on retinal and choroidal layers' thickness. METHODS:: Ninety
      patients with migraine and 40 age-matched healthy participants were enrolled in
      this observational, cross-sectional study. After full ophthalmological
      examination, spectral domain-optical coherence tomography was done for all
      patients measuring the thickness of ganglion cell layer and retinal nerve fiber
      layer. Enhanced depth imaging technique was used to measure the choroidal
      thickness. RESULTS:: There was significant thinning in the superior and inferior
      ganglion cell layers, all retinal nerve fiber layer quadrants, and all choroidal
      quadrants (except for the central subfield) in migraineurs compared to controls.
      The duration of migraine was significantly correlated with ganglion cell layer,
      retinal nerve fiber layer, and all choroidal quadrants, while the severity of
      migraine was significantly correlated with ganglion cell layer and retinal nerve
      fiber layer only. Multiregression analysis showed that the duration of migraine
      is the most important determinant factor of the superior retinal nerve fiber
      layer quadrant (beta = -0.375, p = 0.001) and in all the choroidal quadrants
      (beta = -0.531, -0.692, -0.503, -0.461, -0.564, respectively, p  < 0.001), while
      severity is the most important determinant factor of inferior, nasal, and
      temporal retinal nerve fiber layer quadrants (beta = -0.256, -0.335, -0.308; p  =
      0.036, 0.005, 0.009, respectively) and the inferior ganglion cell layer
      hemisphere (beta = -0.377 and p = 0.001). CONCLUSION:: Ganglion cell layer,
      retinal nerve fiber layer, and choroidal thickness are significantly thinner in
      patients with migraine. The severity of migraine has more significant influence
      in the thinning of ganglion cell layer and retinal nerve fiber layer, while the
      duration of the disease affected the choroidal thickness more.

PMID- 29566546
TI  - Systematic review of the effect of economic compensation and incentives on uptake
      of voluntary medical male circumcision among men in sub-Saharan Africa.
AB  - Voluntary medical male circumcision (VMMC) prevalence in priority countries in
      sub-Saharan Africa, particularly among men aged >=20 years, has not yet reached
      the goal of 80% coverage recommended by the World Health Organization.
      Determining novel strategies to increase VMMC uptake among men >=20 years is
      critical to reach HIV epidemic control. We conducted a systematic review to
      analyze the effectiveness of economic compensation and incentives to increase
      VMMC uptake among older men in order to inform VMMC demand creation programs. The
      review included five qualitative, quantitative, and mixed methods studies
      published in peer reviewed journals. Data was extracted into a study summary
      table, and tables synthesizing study characteristics and results. Results
      indicate that cash reimbursements for transportation and food vouchers of small
      nominal amounts to partially compensate for wage loss were effective, while
      enrollment into lotteries offering prizes were not. Economic compensation
      provided a final push toward VMMC uptake for men who had already been considering
      undergoing circumcision. This was in settings with high circumcision prevalence
      brought by various VMMC demand creation strategies. Lottery prizes offered in the
      studies did not appear to help overcome barriers to access VMMC and qualitative
      evidence suggests this may partially explain why they were not effective.
      Economic compensation may help to increase VMMC uptake in priority countries with
      high circumcision prevalence when it addresses barriers to uptake. Ethical
      considerations, sustainability, and possible externalities should be carefully
      analyzed in countries considering economic compensation as an additional strategy
      to increase VMMC uptake.

PMID- 29566548
TI  - The role of ARFI elastography to evaluate microstructrual changes of patients
      with testicular microlithiasis.
AB  - BACKGROUND: Testicular microlithiasis (TML) is thought to cause microstructural
      changes in the parenchyma of the testis, but it is difficult to demonstrate this
      by ultrasonography. It may be possible to evaluate microstructural changes in the
      testis by Acoustic Radiation Force Impulse (ARFI) elastography, which measures
      tissue stiffness. PURPOSE: To assess the tissue stiffness of testicles of
      children with TML and to compare them with the healthy control group. MATERIAL
      AND METHODS: Between November 2015 and May 2016, 25 pediatric patients with TML
      and 24 healthy children were enrolled in the study (mean age for TML and control
      group 6.7 +/- 3.17 and 7.9 +/- 4.18 years, respectively). Testicular volumes and
      mean shear wave velocity (SWV) values were calculated and compared with each
      other in both groups. RESULTS: There was no significant difference in average
      testicular volumes between the TML group and the control group (1.14 cm3, 1.21
      cm3, respectively; P = 0.986). Mean SWV of the testicles with TML and normal
      testicles with control group was 1.18 +/- 0.22 cm/s and 0.88 +/- 0.11 cm/s,
      respectively. The SWV of the testicles with TML was higher than the normal
      testicles and this was statistically significant ( P < 0.001). CONCLUSION: This
      study has shown that tissue stiffness in patients with TML is increased compared
      to the normal population. ARFI elastography helps the early detection of
      microstructural changes in TML and can be used for screening and follow-up.

PMID- 29566547
TI  - Adaptive and Personalized Plasma Insulin Concentration Estimation for Artificial
      Pancreas Systems.
AB  - BACKGROUND: The artificial pancreas (AP) system, a technology that automatically
      administers exogenous insulin in people with type 1 diabetes mellitus (T1DM) to
      regulate their blood glucose concentrations, necessitates the estimation of the
      amount of active insulin already present in the body to avoid overdosing. METHOD:
      An adaptive and personalized plasma insulin concentration (PIC) estimator is
      designed in this work to accurately quantify the insulin present in the
      bloodstream. The proposed PIC estimation approach incorporates Hovorka's glucose
      insulin model with the unscented Kalman filtering algorithm. Methods for the
      personalized initialization of the time-varying model parameters to individual
      patients for improved estimator convergence are developed. Data from 20 three
      days-long closed-loop clinical experiments conducted involving subjects with T1DM
      are used to evaluate the proposed PIC estimation approach. RESULTS: The proposed
      methods are applied to the clinical data containing significant disturbances,
      such as unannounced meals and exercise, and the results demonstrate the accurate
      real-time estimation of the PIC with the root mean square error of 7.15 and 9.25
      mU/L for the optimization-based fitted parameters and partial least squares
      regression-based testing parameters, respectively. CONCLUSIONS: The accurate real
      time estimation of PIC will benefit the AP systems by preventing overdelivery of
      insulin when significant insulin is present in the bloodstream.

PMID- 29566549
TI  - Mid-term development of the right ventricle in competitive athletes.
AB  - BACKGROUND: Long-term intensive training induces physiological, morphological,
      and functional adaption of the athlete's heart. PURPOSE: To evaluate the
      development of athlete's heart during a mid-term follow-up of competitive
      athletes using cardiac magnetic resonance (CMR). MATERIAL AND METHODS: Eighteen
      competitive long-distance runners and triathletes (age 43 +/- 13 years, 3 women)
      were prospectively examined in a longitudinal follow-up study 5.05 +/- 0.6 years
      after baseline. CMR at 1.5-T was performed for functional and late gadolinium
      enhancement (LGE) imaging. Left ventricular (LV) and right ventricular (RV) end
      diastolic volume (LVEDV, RVEDV) as well as ejection fraction (LVEF, RVEF), LV
      myocardial mass (LVMM), and atrial sizes were determined and compared to baseline
      in matched pairs statistics for paired difference. RESULTS: LVEDV (197 +/- 38 mL
      vs. 196 +/- 38 mL, paired difference -0.9 mL, P = 0.7) and LVEF (62 +/- 7% vs. 62
      +/- 5%, paired difference 0.1%, P = 0.9) did not change during the follow-up
      period, whereas LVMM increased significantly (149 +/- 31 g vs.164 +/- 32 g,
      paired difference 14 g, P < 0.0001). RVEDV significantly increased from 221 +/-
      47 mL at baseline to 230 +/- 52 mL (paired difference 10 mL, P = 0.0033). RVEF
      decreased from baseline 57 +/- 8% to 53 +/- 7% (paired difference -3%, P =
      0.0234). Left atrial size showed no significant changes (24 +/- 5 cm2 vs. 25 +/-
      6 cm2, paired difference 0.5 cm2, P = 0.17) and right atrial size increased
      significantly (30 +/- 5 cm2 vs. 32 +/- 4 cm2, paired difference 2 cm2, P =
      0.0054). CONCLUSION: This study supports the theory of ongoing remodeling in an
      athlete's heart. Predominantly the right heart can further enlarge in a mid-term
      period. This response seems not linearly dependent on a steady, decreased, or
      increased training volume.

PMID- 29566550
TI  - 68Ga-somatostatin receptor analogs and 18F-FDG PET/CT in the localization of
      metastatic pheochromocytomas and paragangliomas with germline mutations: a meta
      analysis.
AB  - BACKGROUND: Metastatic pheochromocytoma and paraganglioma (PCs/PGLs) show high
      germline mutation, and 18F-FDG and 68Ga-DOTA peptide positron emission
      tomography/computed tomography (PET/CT) imaging are recommended for the diagnosis
      of metastatic of PCs. However, there has been lack of direct comparison of the
      two modalities in the diagnosis of metastatic of PCs up to now. PURPOSE: To
      evaluate and compare the value of localization of 68Ga-somatostatin receptor
      analogs and 18F-FDG in the diagnosis of metastatic PCs/PGLs. MATERIAL AND
      METHODS: A comprehensive literature search of PubMed/MEDLINE, ScienceDirect, and
      Web of Science was performed in accordance with the Preferred Reporting Items for
      Systematic Review and Meta-analysis (PRISMA) guidelines published in August 2016.
      We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used
      to evaluate the quality of the methodology of the included studies. RESULTS: This
      meta-analysis included 17 studies (629 patients, average age [mean +/- SD] = 42.7
      +/- 6.3 years). The pooled sensitivity and specificity of 18F-FDG and 68Ga
      peptides were 0.85 (95% confidence interval [CI] = 0.78-0.91) and 0.55 (95% CI =
      0.37-0.73), and 0.95 (95% CI = 0.92-0.97) and 0.87 (95% CI = 0.63-0.96),
      respectively. The area under the sROC curves of the 18F-FDG and 68Ga peptides
      were 0.88 (95% CI = 0.85-0.91) and 0.78 (95% CI = 0.74-0.81), respectively. A
      subgroup analysis demonstrated that the difference at the per-lesion level and
      gene mutation level was significant. CONCLUSION: Compared to 18F-FDG PET/CT, the
      68Ga-somatostatin receptor demonstrated good performance in the localization of
      metastatic PCs/PGLs, especially those with germline mutations. The use of the
      68Ga-somatostatin receptor can be a new tool in the diagnosis of metastatic
      PCs/PGLs.

PMID- 29566551
TI  - In vivo MRI detection of atherosclerosis in ApoE-deficient mice by using tenascin
      C-targeted USPIO.
AB  - BACKGROUND: Atherosclerosis is the main cause of cardiovascular and
      cerebrovascular diseases. Non-invasive molecular imaging to detect and
      characterize the plaques is essential for reducing life-threatening
      cardiovascular events. PURPOSE: To investigate the possibility of the anti
      tenascin-C-USPIO specific probe as a molecular marker of atherosclerotic plaques
      detected by 7.0-T magnetic resonance imaging (MRI). MATERIAL AND METHODS: Twenty
      ApoE-/- mice fed with a high fat diet were used for detecting the aorta arch
      atherosclerotic plaques by 7.0-T MRI at 16 and 24 weeks. Ten mice in the targeted
      group were injected with anti-tenascin-C-USPIO and another ten in the control
      group were injected with pure USPIO (n = 5 each time point in each group).
      Histopathologic examination was used to evaluate the plaques and
      immunohistochemistry analysis was used to compare tenascin-C expression. RESULTS:
      The relative signal intensity (rSI) changes of the targeted group decreased more
      than those of the control group (16 weeks: -15.65 +/- 0.78% vs. -3.43 +/- 2.57%;
      24 weeks: -26.38 +/- 1.54% vs. -11.12 +/- 1.60%, respectively; P < 0.05).
      Histopathological analyses demonstrated visible atherosclerotic plaques formation
      and development over time from 16 weeks to 24 weeks. Tenascin-C expression of the
      plaques at 24 weeks was higher than that at 16 weeks (0.22 +/- 0.04 vs. 0.13 +/-
      0.02, P < 0.05). The MR images correlated well with the progression of
      atherosclerotic plaques. CONCLUSION: Tenascin-C expression increased with the
      progression of atherosclerosis. Anti-tenascin-C-USPIO could provide a useful
      molecular imaging tool for detecting and monitoring atherosclerotic plaques by
      MRI.

PMID- 29566552
TI  - Intraocular lens bicylindric power calculation method: Using both flat and steep
      K readings to improve intraocular lens power prediction.
AB  - PURPOSE: To compare and analyze the accuracy of the refractive outcomes obtained
      in intraocular lens power calculation using the classical calculation method with
      mean keratometry (K) and the calculation method with both K meridians presented
      in this article. METHODS: A total of 62 eyes of 62 subjects who were undergoing
      cataract surgery were included in this study. Optical biometry was performed
      using mean K and Haigis formula for classical intraocular lens calculation
      methods to achieve intraocular lens power; 4 weeks after surgery, prior to
      medical discharge, subjective refraction was made. Alternatively, intraocular
      lens power was calculated with bicylindric method using both keratometry
      readings, obtaining spherocylindrical refractive expected outcomes. Finally,
      results obtained with intraocular lens calculation methods, bicylindric method,
      and Haigis formula were compared. RESULTS: Spherical equivalent calculated by
      classical intraocular lens calculation methods using Haigis formula (H-SE) was 
      0.027 +/- 0.115 D and using bicylindric method (B-SE) was -0.080 +/- 0.222 D.
      Achieved spherical equivalent obtained 4 weeks after surgery (A-SE) was -0.144 +/
      0.268 D. Difference between H-SE and A-SE was -0.117 D (p = 0.002). Difference
      between B-SE and A-SE was not significant (-0.054 D, p = 0.109). Analysis in
      refraction groups showed a positive correlation between A-SE confronted to B-SE
      and H-SE (r = 0.313; p = 0.013 and r = 0.562; p < 0.001, respectively). This
      indicated a reliability in ametropic group prediction of 0.767 in H-SE and 0.843
      in B-SE. CONCLUSION: Intraocular lens calculation with bicylindric method could
      be more accurate and had more reliability than classical intraocular lens
      calculation method. Bicylindric method adds astigmatism control and provides a
      reliable expected spherocylindrical refraction.

PMID- 29566553
TI  - Editorial by Paul Tibbles in dialogue with Ncazelo Ncube.

PMID- 29566554
TI  - Challenges and impossibilities of 'standing alongside' in an intolerable context:
      Learning from refugees and volunteers in the Calais camp.
AB  - This article describes the experience of setting up a psychosocial and
      therapeutic support project in the French Calais refugee camp, by a group of
      family therapists and clinical psychologists from the United Kingdom. This came
      about in response to reports of a humanitarian crisis unfolding on our doorstep,
      with the British government's lack of support for the growing numbers of refugees
      gathering along the UK border with France. The project involved working alongside
      other agencies in the camp to provide psychosocial and resilience-based
      therapeutic support to unaccompanied young people, women, children and their
      families and also to many volunteers in the camp. The process of setting up the
      work is described, as well as the challenges and dilemmas of offering an
      intervention in extremely unsafe and insanitary conditions, where for most the
      experience of trauma was ongoing. The project was informed by systemic-narrative
      practice and community/liberation psychology, which incorporate the political and
      social context. A narrative framework offered a way of drawing on people's
      strengths and resources, rooted in their cultural and social histories and
      helping them connect with preferred identities, which we found to be essential in
      the context of ongoing crisis.

PMID- 29566555
TI  - Positive thinking elevates tolerance: Experimental effects of happiness on
      adolescents' attitudes toward asylum seekers.
AB  - Inducing emotional reactions toward social groups can influence individuals'
      political tolerance. This study examines the influence of incidental fear and
      happiness on adolescents' tolerant attitudes and feelings toward young Muslim
      asylum seekers. In our experiment, 219 16- to 21-year-olds completed measures of
      prejudicial attitudes. After being induced to feel happiness, fear, or no emotion
      (control), participants reported their tolerant attitudes and feelings toward
      asylum-seeking young people. Participants assigned to the happiness condition
      demonstrated more tolerant attitudes toward asylum-seeking young people than did
      those assigned to the fear or control conditions. Participants in the control
      condition did not differ from participants in the fear condition. The
      participants in the happiness condition also had more positive feelings toward
      asylum-seeking young people than did participants in the control condition. The
      findings suggest that one way to increase positive attitudes toward asylum
      seeking young people is to improve general emotional state.

PMID- 29566556
TI  - Stories of trauma in family therapy with refugees: Supporting safe relational
      spaces of narration and silence.
AB  - With the sharp increase of refugees' arrival and resettlement in western
      communities, adequate mental health care forms a pivotal dimension in host
      societies' responses to those individuals and communities seeking protection
      within their borders. Here, clinical literature shows a growing interest in the
      development of family therapy approaches with refugees, in which therapeutic
      practice engages with the pivotal role of refugee family dynamics in posttrauma
      reconstruction and adaptation in resettlement and aims at supporting posttrauma
      reconstruction through strengthening capacities to restore safety, meaning and
      connectedness within family relationships. In this article, we focus on the
      narrative restoration of meaning as central mode of posttrauma reparation and
      explore its specific dynamics and relational complexities in the context of
      therapeutic practice with refugee families. Hereto, we integrate theoretical and
      clinical scholarly work on trauma narration and its intersection with empirical
      findings on trauma communication in refugee families. Furthermore, we develop
      case reflections to illustrate different processes of engaging with trauma
      narration in refugee family therapy. This analysis develops an understanding of
      the multivoiced ways in which refugee families engage with traumatic suffering
      through different modes of expression that may entail both narration and silence
      and explores how family therapeutic practices can engage and mobilize voices of
      narration and silence as relational stories of restoration.

PMID- 29566557
TI  - Mental health of unaccompanied asylum-seeking adolescents previously held in
      British detention centres.
AB  - AIM: To investigate whether the mental health of unaccompanied asylum-seeking
      children (UASC) was negatively affected by having their ages disputed and being
      detained. METHOD: Participants within this cross-sectional study were 35 UASC,
      aged between 13 and 17 when they were detained. Some years later, a team of child
      mental health professionals interviewed them to assess their current mental
      health and to determine, as far as possible, the impact that having their age
      disputed and being detained may have had on their mental health. The Structured
      Clinical Interview for DSM-IV (SCID-IV), Reactions of Adolescents to Traumatic
      Stress (RATS), Stressful Life Events (SLE) and Detention Experiences Checklist-UK
      version (DEC-UK) were administered. RESULTS: The vast majority of UASC reported
      being negatively affected. Based on diagnostic interviews using the SCID-IV, self
      report measures and contemporaneous records, the professionals reported a
      diagnosis of post-traumatic stress disorder (PTSD) developing in 29% ( n = 10),
      PTSD exacerbated in 51% ( n = 18), major depressive disorder (MDD) developing in
      23% ( n = 8) and MDD exacerbated in 40% ( n = 14). A total of 3 years post
      detention, 89% ( n = 31) met diagnostic criteria for psychiatric disorders and
      reported high PTSD symptoms. CONCLUSION: There was a high prevalence of
      psychiatric disorder. The additional stress of age dispute procedures and
      detention was judged to have been harmful.

PMID- 29566558
TI  - In Vivo Imaging of Hydrogen Peroxide with HyPer Probes.
AB  - SIGNIFICANCE: Hydrogen peroxide (H2O2) is a key signaling molecule involved in
      the regulation of both physiological and pathological cellular processes.
      Genetically encoded HyPer probes are currently among the most effective
      approaches for monitoring H2O2 dynamics in various biological systems because
      they can be easily targeted to specific cells and organelles. Since its
      development in 2006, HyPer has proved to be a robust and powerful tool in redox
      biology research. Recent Advances: HyPer probes were used in a variety of models
      to study the role of H2O2 in various redox processes. HyPer has been increasingly
      used in the past few years for in vivo studies, which has already led to many
      important discoveries, for example, that H2O2 plays a key role in the regulation
      of signaling cascades involved in development and aging, inflammation,
      regeneration, photosynthetic signaling, and other biological processes. CRITICAL
      ISSUES: In this review, we focus on the main achievements in the field of redox
      biology that have been obtained from in vivo experiments using HyPer probes.
      FUTURE DIRECTIONS: Further in vivo studies of the role of H2O2 largely depend on
      the development of more suitable versions of HyPer for in vivo models: those
      having brighter fluorescence and a more stable signal in response to
      physiological changes in pH. Antioxid. Redox Signal. 29, 569-584.

PMID- 29566559
TI  - Prognostic accuracy of the SIMBO regarding future return-to-work problems in
      patients with mental and musculoskeletal disorders.
AB  - PURPOSE: A screening instrument (0-100 points) to predict return-to-work (RTW)
      problems was developed. We tested the predictive validity in patients with mental
      diseases (MD) and musculoskeletal diseases (MSD). MATERIALS AND METHODS: A
      prospective multicenter study with questionnaires at admission and 3 months after
      rehabilitation was conducted. Patients with MD and MSD were included. The outcome
      was occurrence of RTW problems during the follow-up. Receiver operating
      characteristic analyses were performed. Sensitivity, specificity, and predictive
      values were calculated for each disease group using the threshold of 27 points.
      RESULTS: There were 401 patients with MD (n = 250) and MSD (n = 151) included in
      the study, and 31.8% and 46.4% reported RTW problems during the follow-up,
      respectively. The area under curve was 0.885 (0.838-0.920) and 0.899 (0.841
      0.943). The sensitivity rates were 87.1% and 87.5% and the specificity rates were
      79.9% and 88.4% for MD and MSD, respectively. The post-test probability of
      experiencing RTW problems was 78.9% for MD and 77.8% for MSD. Analyses including
      only employed patients showed similar results. CONCLUSIONS: The screening
      predicts short-term RTW problems after rehabilitation in patients with mental or
      MSD regardless of employment. The threshold of 27 points was confirmed as
      reasonable, but alternatives in the range of 20-30 points can also be
      recommended. Implications for Rehabilitation The SIMBO is a short and economic
      screening predicting future problems during the return to work (RTW) in patients
      with mental or musculoskeletal diseases. The SIMBO can be recommended to detect
      the initial RTW chance at the beginning of the rehabilitation process. This paper
      implied that there are mainly generic factors predicting the success of an RTW.
      Based on this it is possible to use one screening for different disease groups.

PMID- 29566560
TI  - Overcoming problems of poor drug penetration into bacteria: challenges and
      strategies for medicinal chemists.
AB  - INTRODUCTION: Bacterial cell walls and membranes provide essential protection for
      bacteria against environmental influences. Different bacteria possess different
      cell envelopes and understanding each of these structures is crucial for the
      design of effective antibacterial drugs whose targets are intracellular. Optimal
      properties of drugs that are required for their entry into bacteria are still
      hard to predict. The guidelines that are suitable and well established for the
      penetration of a drug into eukaryotic cells are poorly adaptable to the complex
      world of pathogens. Areas covered: The factors that govern the penetration of
      anti-infection drugs into bacteria are examined and the available strategies to
      overcome this therapeutically very important barrier are reviewed. The areas
      covered include optimization of the physicochemical properties of compounds,
      utilization of iron-chelating compounds, i.e. siderophores, the use of efflux
      pump inhibitors, and of carriers such as liposomes. Expert opinion: Although
      several rules governing permeation have recently been proposed for effective
      antibacterial drugs, none of them has been so far established as the 'golden'
      rule. Thus, new research is needed to find a more general approach on how to
      increase the concentration of antibacterial compounds in bacterial cells.

PMID- 29566561
TI  - A multimodality imaging-compatible insertion robot with a respiratory motion
      calibration module designed for ablation of liver tumors: a preclinical study.
AB  - PURPOSE: To test the accuracy and efficacy of the multimodality imaging
      compatible insertion robot with a respiratory motion calibration module designed
      for ablation of liver tumors in phantom and animal models. To evaluate and
      compare the influences of intervention experience on robot-assisted and
      ultrasound-controlled ablation procedures. METHODS: Accuracy tests on rigid
      body/phantom model with a respiratory movement simulation device and microwave
      ablation tests on porcine liver tumor/rabbit liver cancer were performed with the
      robot we designed or with the traditional ultrasound-guidance by physicians with
      or without intervention experience. RESULTS: In the accuracy tests performed by
      the physicians without intervention experience, the insertion accuracy and
      efficiency of robot-assisted group was higher than those of ultrasound-guided
      group with statistically significant differences. In the microwave ablation tests
      performed by the physicians without intervention experience, better complete
      ablation rate was achieved when applying the robot. In the microwave ablation
      tests performed by the physicians with intervention experience, there was no
      statistically significant difference of the insertion number and total ablation
      time between the robot-assisted group and the ultrasound-controlled group. The
      evaluation by the NASA-TLX suggested that the robot-assisted insertion and
      microwave ablation process performed by physicians with or without experience
      were more comfortable. CONCLUSION: The multimodality imaging-compatible insertion
      robot with a respiratory motion calibration module designed for ablation of liver
      tumors could increase the insertion accuracy and ablation efficacy, and minimize
      the influence of the physicians' experience. The ablation procedure could be more
      comfortable with less stress with the application of the robot.

PMID- 29566563
TI  - Allogeneic hematopoietic cell transplant for relapsed-refractory, marginal zone
      lymphoma: a single-center experience.

PMID- 29566562
TI  - Transurethral high-intensity ultrasound for treatment of stress urinary
      incontinence (SUI): simulation studies with patient-specific models.
AB  - BACKGROUND: Stress urinary incontinence (SUI) is prevalent in adult women,
      attributed to weakened endopelvic supporting tissues, and typically treated using
      drugs and invasive surgical procedures. The objective of this in silico study is
      to explore transurethral high-intensity ultrasound for delivery of precise
      thermal therapy to the endopelvic tissues adjacent to the mid-urethra, to induce
      thermal remodeling as a potential minimally invasive treatment alternative.
      METHODS: 3D acoustic (Rayleigh-Sommerfeld) and biothermal (Pennes bioheat) models
      of the ultrasound applicator and surrounding tissues were devised. Parametric
      studies over transducer configuration [frequency, radius-of-curvature (ROC)] and
      treatment settings (power, duration) were performed, and select cases on patient
      specific models were used for further evaluation. Transient temperature and
      thermal dose distributions were calculated, and temperature and dose metrics
      reported. RESULTS: Configurations using a 5-MHz curvilinear transducer (3.5 * 10
      mm, 28 mm ROC) with single 90 s sonication can create heated zones with 11 mm
      penetration (>50  degrees C) while sparing the inner 1.8 mm (<45  degrees C)
      radial depth of the urethral mucosa. Sequential and discrete applicator rotations
      can sweep out bilateral coagulation volumes (1.4 W power, 15 degrees  rotations,
      600 s total time), produce large volumetric (1124 mm3 above 60 EM43  degrees C)
      and wide angular (~50.5 degrees  per lateral sweep) coverage, with up to 15.6 mm
      thermal penetration and at least 1.6 mm radial urethral protection (<5 EM43 
      degrees C). CONCLUSION: Transurethral applicators with curvilinear ultrasound
      transducers can deliver spatially selective temperature elevations to lateral mid
      urethral targets as a possible means to tighten the endopelvic fascia and
      adjacent tissues.

PMID- 29566564
TI  - Association between preterm labour and pelvic floor muscle function.
AB  - We hypothesised that the pressure on the cervix increases with advancing
      gestation and it may lead to a cervical shortening and cause preterm labour in
      women with weak pelvic floor muscles. The aim of this prospective study was to
      measure vaginal resting pressure and pelvic floor muscle strength in the first
      trimester of pregnancy and to investigate their effects on labour. A study was
      conducted on the pregnant women with a low risk for preterm birth. The pelvic
      floor muscle strength and vaginal resting pressure were assessed in 320 pregnant
      women at their first trimester with a vaginal pressure measurement device. Fifty
      two pregnant women were hospitalised for tocolytic therapy because of spontaneous
      preterm labour. Thirty-two of them (10.2%) had a preterm delivery despite the
      tocolytic therapy. Both the vaginal resting pressure (p = .009, 95%CI: 0.8; 5.9)
      and the pelvic floor muscle strength (p = .01, 95%CI: 3.5; 13.1) were
      significantly lower in the women with a preterm labour. Impact statement What is
      already known on this subject? The pelvic floor muscles have an essential role in
      continence and provide support to the pelvic organs. They also have an impact on
      labour. The pelvic floor muscles should distend to allow the passage of the
      foetus during labour. The rotation and flexion of the foetal head is due to the
      pelvic floor resistance. The effect of a vaginal birth on the pelvic floor's
      function is readily understood. On the other hand, the effect of the pelvic floor
      muscle function on labour is still controversial. What do the results of this
      study add? This prospective study showed that there is a negative association
      between the pelvic floor muscle strength and preterm labour. This is the first
      clinical study indicating that weak pelvic floor muscles may cause a preterm
      labour. What are the implications of these findings for clinical practice and/or
      further research? Pelvic floor physical therapy may be an alternative preventive
      strategy to reduce the risk of a spontaneous preterm birth.

PMID- 29566565
TI  - In the aftermath of SPRINT: further comparison of unattended automated office
      blood pressure measurement and 24-hour blood pressure monitoring.
AB  - AIMS: Several papers reported that unattended automated office blood pressure
      (uAutoOBP) is closely related to daytime ambulatory blood pressure monitoring
      (ABPM). In the present study, we aim to study uAutoOBP and its relation to 24
      hour ABPM and ABPM variability. MATERIAL AND METHODS: Stable treated hypertensive
      subjects were examined in two Czech academic hypertension centres. uAutoOBP was
      measured with the BP Tru device; attended BP three times with auscultatory method
      (AuscOBP) by the physician. ABPM was performed within one week from the clinical
      visit. RESULTS: Data on 98 subjects aged 67.7 +/- 9.3 years with 24-hour ABPM
      120.3 +/- 10.6/72.7 +/- 7.9 mm Hg are reported. uAutoOBP was lower than 24-hour
      (by -5.2 +/- 11.3/-0.5 +/- 6.9 mm Hg) and daytime (by -6.7 +/- 12.82.4 +/- 8.0 mm
      Hg) ABPM and the individual variability of the difference was very large (up to
      30 mm Hg). The correlation coefficients between ABPM and uAutoOBP were similar
      compared to AuscOBP (p >= .17). Variability of uAutoOBP, but not AuscOBP,
      readings during one clinical visit was related to short-term blood pressure
      variability of ABPM. The difference between AuscOBP and uAutoOBP was larger in
      patients with white-coat effect compared to other blood pressure control groups
      (25.1 +/- 7.0 vs. 2.2 +/- 10.3 mm Hg; p = .0036). CONCLUSIONS: Our study shows
      that uAutoOBP is not good predictor of ambulatory blood pressure monitoring, not
      even of the daytime values. It might, however, indicate short-term blood pressure
      variability and, when compared with AuscOBP, also detect patients with white-coat
      effect.

PMID- 29566566
TI  - Combination of three-dimensional ultrasound measurement of foetal adrenal gland
      enlargement and placental alpha microglobulin-1 for the prediction of the timing
      of delivery within seven days in women with threatened preterm labour and preterm
      labour.
AB  - The aim of this study was to predict the timing of delivery within seven days in
      singleton pregnant women with threatened preterm labour and preterm labour by
      using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland
      volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha
      microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton
      pregnant women at 22-36+6 weeks of gestation who presented with threatened
      preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement
      of the whole foetal adrenal gland and of the foetal adrenal zone were performed.
      Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One
      hundred and fifty-four pregnant women were included into the study. Eighty-four
      pregnant women had threatened preterm labour and seventy pregnant women had
      preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use
      of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG
      1 test in combination increased sensitivity; if one parameter was positive, the
      sensitivity, specificity, positive predictive value and negative predictive value
      were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing
      of delivery within seven days. The combination of foetal adrenal gland
      enlargement and PAMG-1 increased sensitivity for the prediction of the timing of
      delivery within seven days in pregnant women presenting with threatened preterm
      labour and preterm labour. Impact Statement What is already known on this
      subject? An increased foetal adrenal gland volume is significantly correlated
      with the risk of preterm birth. What do the results of this study add? The
      combination of a foetal adrenal gland enlargement and a placental alpha
      microglobulin-1 increased sensitivity for the prediction of the timing of
      delivery within seven days in pregnant women presenting with threatened preterm
      labour and preterm labour. What are the implications of these findings for
      clinical practice and/or further research? The combination of a foetal adrenal
      gland enlargement and placental alpha microglobulin-1 may be used for the
      prediction of the timing of delivery within seven days in pregnant women
      presenting with threatened preterm labour and with preterm labour.

PMID- 29566567
TI  - Exploring Dutch surgeons' views on volume-based policies: a qualitative interview
      study.
AB  - Objective In many countries, the evidence for volume-outcome associations in
      surgery has been transferred into policy. Despite the large body of research that
      exists on the topic, qualitative studies aimed at surgeons' views on, and
      experiences with, these volume-based policies are lacking. We interviewed Dutch
      surgeons to gain more insight into the implications of volume-outcome policies
      for daily clinical practice, as input for effective surgical quality improvement.
      Methods Semi-structured interviews were conducted with 20 purposively selected
      surgeons from a stratified sample for hospital type and speciality. The
      interviews were recorded, transcribed verbatim and underwent inductive content
      analysis. Results Two overarching themes were inductively derived from the data:
      (1) minimum volume standards and (2) implications of volume-based policies.
      Although surgeons acknowledged the premise 'more is better', they were critical
      about the validity and underlying evidence for minimum volume standards. Patients
      often inquire about caseload, which is met with both understanding and
      discomfort. Surgeons offered many examples of controversies surrounding the
      process of determining thresholds as well as the ways in which health insurers
      use volume as a purchasing criterion. Furthermore, being held accountable for
      caseload may trigger undesired strategic behaviour, such as unwarranted
      operations. Volume-based policies also have implications for the survival of low
      volume providers and affect patient travel times, although the latter is not
      necessarily problematic in the Dutch context. Conclusions Surgeons in this study
      acknowledged that more volume leads to better quality. However, validity issues,
      undesired strategic behaviour and the ways in which minimum volume standards are
      established and applied have made surgeons critical of current policy practice.
      These findings suggest that volume remains a controversial quality measure and
      causes polarization that is not conducive to a collective effort for quality
      improvement. We recommend enforcing thresholds that are based on the best
      achievable level of consensus and assessing additional criteria when passing
      judgement on quality of care.

PMID- 29566569
TI  - Using physical objects with young children in 'face-to-face' and telehealth
      speech and language therapy.
AB  - PURPOSE: Speech language therapists increasingly are using telehealth to enhance
      the accessibility of their services. It is unclear, however, how play-based
      therapy for children can be delivered via telehealth. In particular, modalities
      such as videoconferencing do not enable physical engagement between therapists
      and clients. The aim of our reported study was to understand how physical objects
      such as toys are used in similar and different ways across videoconferenced and
      "face-to-face" (hereafter, "in-person") therapy. METHODS: We used conversation
      analytic methods to compare video-recorded therapy sessions for children
      delivered across in-person and telehealth settings. Utilising a broader corpus of
      materials, our analysis focused on four client-therapist dyads: two using
      videoconferencing, and two who met in-person. RESULTS: Both videoconferencing and
      in-person sessions enabled routine affordances and challenges for delivering
      therapy. Within in-person therapy, therapists made access to objects contingent
      upon the client producing some target expression. This contingency usually was
      achieved by restricting physical access to these objects. Restricting access to a
      toy was not necessary in videoconferenced therapy; therapists instead used
      techniques to promote engagement. CONCLUSIONS: When delivering play-based therapy
      via telehealth, our study demonstrates how practitioners adapt the intervention
      to suit the particular medium of its delivery. Implications for Rehabilitation
      Telehealth enhances equitable access for those who cannot physically access
      rehabilitation services. Telehealth modalities can create practical challenges,
      however, when delivering interventions such as play-based therapy. Practitioners
      should intentionally adapt telehealth interventions to suit the particular
      telehealth modality they are using.

PMID- 29566568
TI  - Sexual Responses Are Facilitated by High-Order Contextual Cues in Females but Not
      in Males.
AB  - Sexual responses are thought to be controlled by a brain module called the sexual
      module. Sexual strategies of males and females vary to a great extent, and sexual
      responses of males and females may be affected by their sexual strategies.
      However, the current view of the sexual module is that of a unisex module. This
      might be questionable since brain modules are defined as evolved cognitive
      mechanisms to solve adaptive problems which are different for males and females.
      We hypothesize that the sexual module responds differently in the presence of
      complex (high-order) contextual cues that are related to gender-dimorphic sexual
      strategies in males and females. We conducted a priming experiment in which
      stimuli related to sexual strategies were disentangled from their sexual meaning.
      Nonsexual priming pictures related to either economic resources or social
      interactions preceded a sexual-target picture in order to test whether the primes
      were able to modulate the subjective sexual response to the sexual target. In a
      control condition, priming pictures without relation to mating preferences but
      with similar emotional impact were presented. In males, sexual responses were
      similar in the experimental and control conditions. In females, however, primes
      related to economic resources or social interactions modulated sexual arousal
      significantly more than the control primes. Our findings suggest that brain
      modules dedicated to process the experimental primes were functionally connected
      with the sexual module in females more than in males, making females' sexual
      responses more prone to the impact of high-order cultural cues than males' sexual
      responses. A gender-dimorphic connectivity of the sexual module may be the way in
      which gender-dimorphic sexual strategies are implemented in the human mind.

PMID- 29566570
TI  - Three-dimensional assessment of the asymptomatic and post-stroke shoulder: intra
      rater test-retest reliability and within-subject repeatability of the palpation
      and digitization approach.
AB  - PURPOSE: Altered three-dimensional (3D) joint kinematics can contribute to
      shoulder pathology, including post-stroke shoulder pain. Reliable assessment
      methods enable comparative studies between asymptomatic shoulders of healthy
      subjects and painful shoulders of post-stroke subjects, and could inform
      treatment planning for post-stroke shoulder pain. The study purpose was to
      establish intra-rater test-retest reliability and within-subject repeatability of
      a palpation/digitization protocol, which assesses 3D clavicular/scapular/humeral
      rotations, in asymptomatic and painful post-stroke shoulders. METHODS: Repeated
      measurements of 3D clavicular/scapular/humeral joint/segment rotations were
      obtained using palpation/digitization in 32 asymptomatic and six painful post
      stroke shoulders during four reaching postures (rest/flexion/abduction/external
      rotation). Intra-class correlation coefficients (ICCs), standard error of the
      measurement and 95% confidence intervals were calculated. RESULTS: All ICC values
      indicated high to very high test-retest reliability (>=0.70), with lower
      reliability for scapular anterior/posterior tilt during external rotation in
      asymptomatic subjects, and scapular medial/lateral rotation, humeral horizontal
      abduction/adduction and axial rotation during abduction in post-stroke subjects.
      All standard error of measurement values demonstrated within-subject
      repeatability error <=5 degrees  for all clavicular/scapular/humeral
      joint/segment rotations (asymptomatic <=3.75 degrees ; post-stroke <=5.0 degrees
      ), except for humeral axial rotation (asymptomatic <=5 degrees ; post-stroke <=15
      degrees ). CONCLUSIONS: This noninvasive, clinically feasible
      palpation/digitization protocol was reliable and repeatable in asymptomatic
      shoulders, and in a smaller sample of painful post-stroke shoulders. Implications
      for Rehabilitation In the clinical setting, a reliable and repeatable noninvasive
      method for assessment of three-dimensional (3D) clavicular/scapular/humeral joint
      orientation and range of motion (ROM) is currently required. The established
      reliability and repeatability of this proposed palpation/digitization protocol
      will enable comparative 3D ROM studies between asymptomatic and post-stroke
      shoulders, which will further inform treatment planning. Intra-rater test-retest
      repeatability, which is measured by the standard error of the measure, indicates
      the range of error associated with a single test measure. Therefore, clinicians
      can use the standard error of the measure to determine the "true" differences
      between pre-treatment and post-treatment test scores.

PMID- 29566571
TI  - Respiratory measures in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular
      disease that causes skeletal muscle weakness, including muscles involved with
      respiration. Death often results from respiratory failure within 3-5 years.
      Monitoring respiratory status is therefore critical to ALS management, as
      respiratory/pulmonary function tests (PFTs) are used to make decisions including
      when to initiate noninvasive ventilation. Understanding the different respiratory
      and PFTs as they relate to disease progression and survival may help determine
      which tests are most suitable. METHODS: This review describes the tests used to
      assess respiratory muscle and pulmonary function in patients with ALS and the
      correlations between different respiratory measures and clinical outcomes
      measures. RESULTS: The most commonly used measurement, forced vital capacity
      (VC), has been shown to correlate with clinical milestones including survival,
      but also requires good motor coordination and facial strength to form a tight
      seal around a mouthpiece. Other tests such as slow VC, sniff inspiratory
      pressure, or transdiaphragmatic pressure with magnetic stimulation are also
      associated with distinct advantages and disadvantages. CONCLUSIONS: Therefore,
      how and when to use different tests remains unclear. Understanding how each test
      relates to disease progression and survival may help determine which is best
      suited for specific clinical decisions.

PMID- 29566573
TI  - Spontaneous prelabour recurrent uterine rupture after laparoscopic myomectomy.

PMID- 29566572
TI  - Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular
      Tissue.
AB  - OBJECTIVE: Tetrahydrobiopterin (BH4) is the essential cofactor of endothelial
      nitric oxide synthase (eNOS) and intracellular levels of BH4 is regulated by
      oxidative stress. The aim of this paper was to describe the influence of
      exogenous endothelin-1 on intracellular BH4 and its oxidation products
      dihydrobiopterin (BH2) and biopterin (B) in a wide range of vascular tissue.
      DESIGN: Segments of internal mammary artery (IMA) and human saphenous vein (SV)
      from 41 patients undergoing elective surgery were incubated in ET-1 (0.1 MUM).
      Aorta and lung from transgenic mice overexpressing ET-1 in the endothelium (ET
      TG) were analysed with regards to intracellular biopterin levels. Human umbilical
      vein endothelial cells (HUVEC) were incubated in ET-1 (0.1 MUM) and intracellular
      biopterin levels were analysed. From 6 healthy women undergoing caesarean
      section, subcutaneous fat was harvested and the resistance arteries in these
      biopsies were tested for ET-mediated endothelial dysfunction. RESULTS: In HUVEC,
      exogenous ET-1 (0.1 MUM) did not significantly change intracellular BH4, 1.54 +/-
      1.7 vs 1.68 +/- 1.8 pmol/mg protein; p = .8. In IMA and SV, exogenous ET-1(0.1
      MUM) did not change intracellular BH4 n = 10, p = .4. In aorta from wild type vs
      ET-TG mice there was no significant difference in intracellular BH4 between the
      groups: 1.3 +/- 0.49 vs 1.23 +/- 0.3 pmol/mg protein; p = .6. In resistance
      arteries (n = 6) BH4 together with DTE (an antioxidant) was not able to prevent
      ET-mediated endothelial dysfunction. CONCLUSION: ET-1 did not significantly alter
      intracellular tetrahydrobiopterin levels in IMA, SV, HUVEC or aorta from ET-TG
      mice. These findings are important for future research in ET-1 mediated
      superoxide production and endothelial dysfunction.

PMID- 29566574
TI  - Bcl-2/E1B-19KD-Interacting Protein 3/Light Chain 3 Interaction Induces Mitophagy
      in Spinal Cord Injury in Rats Both In Vivo and In Vitro.
AB  - Autophagy and mitophagy have been shown to occur in spinal cord injury (SCI). Bcl
      2/E1B-19KD-interacting protein 3 (BNIP3) and its homologue, NIX, have been
      implicated in the regulation of mitophagy. The aim of this work was to
      characterize the mechanisms and role of BNIP3 in SCI-associated mitophagy. Our
      data showed that BNIP3, targeted to mitochondria, interacted with microtubule
      associated protein 1A/1B-light chain 3 (LC3), which is targeted to
      autophagosomes, thus forming a mitochondria-BNIP3-LC3-autophagosome complex and
      resulting in mitophagy. Downregulation of BNIP3 by RNA interference strengthened
      the mitochondrial function and decreased cell death in spinal cord neurons under
      hypoxia. Particularly, BNIP3 knockdown significantly improved neurological
      recovery and the number of neuronal nuclei-positive cells post-SCI in rats. The
      present study demonstrated that BNIP3 interacts with LC3 to induce mitophagy,
      whereas its inhibition provided protective neuronal effects in SCI rat models
      both in vivo and in vitro.

PMID- 29566575
TI  - Evaluating Comprehensive State Tobacco Prevention and Control Programs Using an
      Outcome Indicator Framework.
AB  - The outcome indicator framework helps tobacco prevention and control programs
      (TCPs) plan and implement theory-driven evaluations of their efforts to reduce
      and prevent tobacco use. Tobacco use is the single-most preventable cause of
      morbidity and mortality in the United States. The implementation of public health
      best practices by comprehensive state TCPs has been shown to prevent the
      initiation of tobacco use, reduce tobacco use prevalence, and decrease tobacco
      related health care expenditures. Achieving and sustaining program goals require
      TCPs to evaluate the effectiveness and impact of their programs. To guide
      evaluation efforts by TCPs, the Centers for Disease Control and Prevention's
      Office on Smoking and Health developed an outcome indicator framework that
      includes a high-level logic model and evidence-based outcome indicators for each
      tobacco prevention and control goal area. In this article, we describe how TCPs
      and other community organizations can use the outcome indicator framework in
      their evaluation efforts. We also discuss how the framework is used at the
      national level to unify tobacco prevention and control efforts across varying
      state contexts, identify promising practices, and expand the public health
      evidence base.

PMID- 29566576
TI  - Health Marketing for the Massachusetts Childhood Obesity Research Demonstration
      Study: A Case Study.
AB  - INTRODUCTION: This case study describes the Massachusetts Childhood Obesity
      Research Demonstration Study (MA-CORD) health marketing campaign, examines the
      strategies used in such campaigns, and offers lessons learned to improve health
      marketing for future interventions. MA-CORD Health Marketing Components and
      Implementation. The three main components were an outdoor printed advertisement
      and texting campaign, social media with a focus on Facebook, and the Summer
      Passport Program, an event-based initiative in parks for children. The
      advertisements consisted of billboards, bus advertisements, and handouts. The
      text messaging component, which required families to actively text a keyword to
      join, had a low opt-in rate. Facebook page "likes" increased from 1,024 to 1,453
      in New Bedford and from 175 to 1,091 in Fitchburg. Fitchburg received technical
      assistance and paid for ads on Facebook. The Summer Passport participation in
      parks ranged from 120 to 875 children with participation in the free park lunch
      program doubling in Fitchburg. DISCUSSION: Key lessons learned are engage
      communication experts from each community at the beginning of the project, use
      text messaging components with in-person staff onsite to assist participants in
      the opt-in process, build momentum for a Facebook presence through purchasing
      Facebook advertisements, and partner with local park departments for programming.

PMID- 29566577
TI  - Self-Care Posters Serve as a Low-Cost Option for Physical Activity Promotion of
      Hospital Nurses.
AB  - Hospital nurses play an important role in the nation's short- and long-term
      patient care. At the same time, nurses often experience high levels of
      occupational stress and participate in low levels of physical activity (PA). The
      purpose of this study was to examine the impact of self-monitoring and a poster
      campaign on the PA behaviors of hospital nurses. Motivational and instructional
      exercise posters were hung in break rooms of experimental units and replaced
      biweekly for 8 weeks. A total of 26 nurses (control: n = 13; experimental: n =
      13) wore accelerometers for 3 workdays pre-, mid-, and postintervention.
      Participants were provided a step counter at baseline and a PA report at each
      stage. Moderate to vigorous PA (MVPA) and step count (SC) increased pre- to
      midintervention for control (MVPA: 14.8 +/- 7.6%; SC: 19.1 +/- 7.8%) and
      experimental (MVPA: 26.7 +/- 18.5%, SC: 17.6 +/- 8.3%) participants. Physical
      activity levels returned to baseline postintervention for control ( p > .05) and
      increased mid- to postintervention for experimental (MVPA: 16.2 +/- 5.2%, SC:
      10.7 +/- 4.7%, p < .05) participants. In conclusion, a low-cost, self-care poster
      campaign may increase PA levels of hospital nurses when combined with
      personalized PA feedback.

PMID- 29566578
TI  - Aminobenzisoxazole compounds as agonists of alpha7 nicotinic acetylcholine
      receptors: a patent evaluation (WO 2017027600).
AB  - INTRODUCTION: alpha 7 subtype nicotinic acetylcholine receptor (alpha7 nAChR)
      ligands, that is, ligands that interact with the orthosteric or allosteric
      binding sites of alpha7 nAChR, hold great potential for several therapeutic
      applications. Numerous compounds have been designed targeting alpha7 nAChR but
      most of them cannot be used therapeutically for various reasons. Areas covered:
      The patent application describes a series of germinal substituted
      aminobenzisoxazole compounds as alpha7 nAChR ligands. These compounds were
      claimed as potential therapeutics for treating and/or improving cognitive
      function. All of the (R)-stereoisomer presented high binding activities for
      alpha7 nAChR and several compounds displayed excellent selectivity over 5-HT3R.
      Expert opinion: The privileged structure-derived modification via bioisosterism
      and scaffold hopping is an important approach for seeking novel alpha7 nAChR
      ligands. The claimed germinal substituted aminobenzisoxazole derivatives with low
      tPSA values as well as low number of hydrogen bond donors and acceptors are
      supposed to have sufficient BBB penetration. Although there is a lack of
      essential biological data and the molecular mechanisms are not clear, these
      compounds stand for a new type of alpha7 nAChR ligands and deserve further
      studies.

PMID- 29566579
TI  - The effect of ocular lubricants containing benzalkonium chloride on nasal mucosal
      flora.
AB  - PURPOSE: The effect of ocular artificial teardrop containing benzalkonium
      chloride (BAC) on nasal mucosa was investigated. MATERIALS AND METHODS: There
      were two different treatment trial groups. Each dry eye syndrome (DES) patient
      received the ocular lubricant treatment four times a day in both groups (one
      group containing BAC, the other group was not). Moistened sterile cotton-tipped
      applicators were placed in both nostrils and were immediately cultured prior to
      ocular lubricant treatment and at the end of treatment trial. The bacterial
      culture-positivity rate, species of bacteria, and drug sensitivity were recorded
      in the two groups during pre-treatment and post-treatment. RESULTS: There were 20
      patients in each group with a mean age of 53.14 years (36 female, 4 male). At the
      beginning of the treatment trial, Staphylococcus epidermidis was the most
      frequently isolated organism from the nasal cavity accounting in 24/40 patients
      (60%). Of the 40 organisms isolated from the nares prior to treatment trial, 37
      (92.5%) were sensitive to gentamycin. At the end of 1 month of treatment trial in
      patients who were treated with ocular lubricants containing BAC, none of the
      nasal cultures showed growth of any organisms. However, patients who were treated
      with ocular lubricants not containing BAC demonstrated persistent positive nasal
      cultures with the same species and the same antibiotic susceptibility profile at
      the end of the treatment trial period. CONCLUSION: Topically applied ocular
      lubricants including BAC has an anti-bacterial activity on nasal flora in DES
      patients.

PMID- 29566580
TI  - Structural exploration of hydroxyethylamines as HIV-1 protease inhibitors: new
      features identified.
AB  - The current study deals with chemometric modelling strategies (Naive Bayes
      classification, hologram-based quantitative structure-activity relationship
      (HQSAR), comparative molecular field analysis (CoMFA) and comparative molecular
      similarity index analysis (CoMSIA)) to explore the important features of
      hydroxylamine derivatives for exerting potent human immunodeficiency virus-1 (HIV
      1) protease inhibition. Depending on the statistically validated reliable and
      robust quantitative structure-activity relationship (QSAR) models, important and
      crucial structural features have been identified that may be responsible for
      enhancing the activity profile of these hydroxylamine compounds. Arylsulfonamide
      function along with methoxy or fluoro substitution is important for enhancing
      activity. Bulky steric substitution at the sulfonamide nitrogen disfavours
      activity whereas smaller hydrophobic substitution at the same position is found
      to be favourable. Apart from the crucial oxazolidinone moiety, pyrrolidine,
      cyclic urea and methyl ester functions are also responsible for increasing the
      HIV-1 protease inhibitory profile. Observations derived from these modelling
      studies may be utilized further in designing promising HIV-1 protease inhibitors
      of this class.

PMID- 29566581
TI  - Investigation of bacteremia after debonding procedures.
AB  - OBJECTIVE: The purpose of this study is to investigate the effect of debonding
      procedures after completion of orthodontic treatments on bacteremia. MATERIALS
      AND METHODS: Twenty-eight patients who were treated with fixed orthodontic
      treatment at the Faculty of Dentistry's Department of Orthodontics at Gaziantep
      University and who had an indication of debonding were selected for this study,
      and blood samples were taken from these patients at different times and examined
      for bacteremia. Blood culture samples were taken from the antecubital veins of
      the patients prior to debonding (T0), immediately after removing the bracket
      (T1), and immediately after cleaning the composite residues and plaque deposits
      on the enamel surface (T2). The blood samples were then inoculated in blood
      culture bottles and investigated for bacterial growth. RESULTS: The results
      showed that there was no bacterial growth in the blood samples taken at T0 and
      T1, whereas 10 of the blood culture samples taken at T2 showed bacterial growth
      including the following bacteria; Streptococcus viridans, Streptococcus mitis,
      Streptococcus parasanguinis, Streptococcus salivarius, Streptococcus oralis,
      Staphylococcus aureus, Actinomyces oris, Actinomyces naeslundii and Klebsiella
      pneumoniae. CONCLUSION: It was concluded that patients in the risk group could
      develop bacteremia during debonding procedures. The presence of these bacteria in
      sterile blood suggested the possibility of bacterial endocarditis.

PMID- 29566582
TI  - Reducing mutans streptococci and caries development by Lactobacillus paracasei
      SD1 in preschool children: a randomized placebo-controlled trial.
AB  - OBJECTIVE: To examine a reducing effect of Lactobacillus paracasei SD1 on MS and
      caries in preschool children. MATERIALS AND METHODS: A total of 124 children,
      aged 1.5-5 years old, participated and were randomly assigned to the probiotic or
      control group. The probiotic group received L. paracasei SD1-milk and the control
      group received standard-milk once daily for 3 months. MS/lactobacilli were
      enumerated and the caries score was examined. Association between probiotic
      consumption and bacterial level, or caries progression was assessed by a
      multivariate logistic regression. This study was registered at the Thai-Clinical
      Trials-Registry (TCTR20140903001). RESULTS: Probiotic was found to be a factor
      associated with the MS level. Children in the probiotic group had a significantly
      lower risk of an increase in the MS level than in the control group after
      receiving the probiotic milk at 3- and 4-months with p < .001 and p = .040,
      respectively. Probiotic significantly reduced the risk for caries compared to the
      control group (p = .016). There were no adverse effects or non-compliance
      reported in either group. CONCLUSIONS: Consumption of milk powder containing L.
      paracasei SD1 resulted in a reduction of both salivary MS and delayed new caries
      development, and the strain is safe for use in young children. Results suggest
      that L. paracasei SD1 may be an alternative way for caries prevention in young
      children.

PMID- 29566583
TI  - Benefits of upgrading to the Nucleus(r) 6 sound processor for a wider clinical
      population.
AB  - OBJECTIVES: To determine whether a large clinical group of cochlear implant (CI)
      recipients demonstrated a difference in sentence recognition in noise when using
      their pre-upgrade sound processor compared to when using the Nucleus 6 processor,
      and to examine the impact of the following factors: implant type, sound processor
      type, age, or onset of hearing loss. METHODS: A file review of 154 CI recipients
      (aged 7-92 years old) who requested an upgrade to the Nucleus 6 sound processor
      at the Cochlear Care Centre Melbourne was conducted. 105 recipients had complete
      data collected according to the protocol. A repeated measures, single subject
      design was used. Performance of CI recipients was compared with their pre-upgrade
      sound processor versus the Nucleus 6 processor using the Australian Sentence Test
      in Noise. RESULTS: Group performance of CI recipients improved by 4.7 dB with the
      Nucleus 6 compared with the pre-upgrade sound processor. The benefit was not
      affected by pre-upgrade sound processor type or implant type (including older
      implant types and sound processors), age or onset of hearing loss (pre-lingual
      versus post-lingual). CONCLUSION: This study confirmed that a clinical group of
      CI recipients obtained a significant benefit when upgrading to the Nucleus 6
      sound processor.

PMID- 29566584
TI  - Gene drives may be the next step towards sustainable control of malaria.

PMID- 29566585
TI  - Evaluation of epidemiological, clinical, and laboratory features and mortality of
      144 HIV/AIDS cases in Turkey.
AB  - Background The number of HIV/AIDS cases in Turkey is increasing rapidly, as is
      the number of cases worldwide. The aim of this study is to evaluate the
      characteristics of the clinical and laboratory findings and epidemiological
      features of HIV/AIDS patients to obtain useful data on the epidemic type and
      transmission routes associated with Turkey and to identify risk factors for
      mortality. Methods The patient records of 144 HIV-infected patients who were
      admitted to our clinic between 2000 and 2015 were analyzed retrospectively.
      Results Most of the cases (55%) were diagnosed due to the detection of anti-HIV
      positive individuals without clinical symptoms. The mean CD4 + lymphocyte count
      on first admission was 108 cells/MUL for those admitted before 2009 and 265
      cells/MUL for those admitted after 2009 (p = 0.003). When the pre- and post-2009
      groups were compared for the status of the disease, 55.6 and 44.4% of patients
      were in the AIDS stage, respectively (p = 0.04). The most noted opportunistic
      infection was mycobacterial, and throughout the follow-up, 31.2% of the cases
      were fatal. Conclusions Early diagnosis of HIV infection can have a direct impact
      on prognosis and survival. Therefore, screening laboratory investigations should
      be extended, particularly in high-risk groups.

PMID- 29566586
TI  - Efficacy and Safety of Basal Insulin/GLP-1 Receptor Agonist Used in Combination
      for Type 2 Diabetes Management.
AB  - PURPOSE: The purpose of this article is to review the efficacy, safety, and place
      in therapy of insulin degludec/liraglutide (IDegLira) and insulin
      glargine/lixisenatide (IGlarLixi) in the treatment of type 2 diabetes mellitus.
      SUMMARY: Type 2 diabetes is a condition affecting nearly 30 million American
      adults. Management of type 2 diabetes is complex and multifactorial. Using
      medications targeted at a variety of the physiologic defects known to contribute
      to the development of type 2 diabetes allows for a patient-specific approach to
      care. Utilizing combination products is a way to target several areas of the
      disease while decreasing the complexity and burden to the patient. Basal
      insulin/glucagon-like peptide-1 (GLP-1) agonist combination products have the
      benefit of being highly efficacious while having favorable effects on weight,
      reduced gastrointestinal adverse effects, and low hypoglycemic risks compared to
      the individual agents used alone. CONCLUSION: This article will review 2 basal
      insulin/GLP-1 agonist combination products, IDegLira and IGlarLixi, which were
      approved in November 2016.

PMID- 29566588
TI  - Effectiveness of ReSET; a strategic executive treatment for executive
      dysfunctioning in patients with Parkinson's disease.
AB  - In this multicentre randomised controlled trial (RCT), 43 patients with
      Parkinson's disease (PD) were randomly allocated to either the experimental
      condition receiving cognitive rehabilitation including strategy training (ReSET;
      Strategic Executive Treatment, n = 24) or to the control condition receiving
      computerised repetitive practice training for attention (Cogniplus, n = 16). We
      expected that strategy training (ReSET) would be more effective than cognitive
      training (Cogniplus) in improving patients' everyday life executive functioning.
      Neuropsychological assessment was administered at baseline, at 2 weeks and 3-5
      months post-treatment. Primary outcome measure was the Role Resumption List
      (RRL). Secondary outcome measures were treatment goal attainment (TGA),
      Dysexecutive Questionnaire (DEX), Parkinson's Disease Questionnaire (PDQ-39),
      Zarit Burden Interview (ZBI) and neuropsychological tests. No effects of
      treatment were found on the primary outcome measure and on neuropsychological
      tests, except for one test of attention. At 2 weeks and 3-5 months post
      treatment, PD patients in both the ReSET and Cogniplus group reported a
      significant improvement in everyday life executive functioning, as measured with
      TGA and the DEX-self, with an advantage for ReSET only shortly after treatment.
      Given these results and that PD patients were able to adhere to these treatments
      despite their motor symptoms and fatigue (i.e., the drop-out rate was small), we
      conclude that both strategy training and cognitive training for impairments in EF
      might be beneficial and feasible for PD patients.

PMID- 29566587
TI  - Hypnosis as adjunct therapy to conscious sedation for venous access device
      implantation in breast cancer: A pilot study.
AB  - BACKGROUND: Recent reviews support that hypnosis has great potential for reducing
      pain and anxiety during mini-invasive surgery. Here, we assessed the feasibility
      of hypnotic induction session as adjunct therapy in conscious sedation for venous
      access device implantation. Primary outcomes were safety and patient
      satisfaction. METHODS: Thirty consecutive women with breast cancer were proposed
      adjunct of hypnosis before implantation under conscious sedation (midazolam: 0.5
      mg +/- bolus of Ketamin: 5 mg on demand) indicated for chemotherapy. Self
      hypnosis was programmed and guided by one of two trained anesthesiologists.
      Implantation was performed by one of two experimented surgeons. It consisted of
      blind subclavian implantation of Braun ST 305 devices using a percutaneous
      technique adapted from Selinger's procedure. Clinical data were prospectively
      collected and retrospectively analyzed. A comprehensive custom-made questionnaire
      recorded patient satisfaction. RESULTS: In all, 30/30 patients consented to the
      procedure. The median age was 54 years (range: 35-77 years). The primary
      procedure was successful in 29/30. One case was converted into internal jugular
      vein access after a first attempt. Median length time of the implantation
      procedure in the operative room was 20 min (range: 10-60 min). Median length time
      in the recovery room preceding home discharge was 65 min (range: 15-185 min).
      None of the patients suffered complications. The satisfaction rate was >=90%,
      27/30 patients would get hypnosis in case of reimplantation if necessary and
      27/30 would recommend this procedure to others. CONCLUSION: Hypnosis under
      conscious sedation appears feasible and safe for port implantation under
      conscious sedation in cancer patients. Further studies would determine the exact
      value of hypnosis effectiveness.

PMID- 29566589
TI  - Obstructive sleep apnea and risk of aortic dissection: A meta-analysis of
      observational studies.
AB  - Objectives Obstructive sleep apnea acts as a potential risk factor for the
      development of cardiovascular disease. We undertook collaborative meta-analyses
      to clarify the risk of aortic dissection among adults suffering obstructive sleep
      apnea. Methods A systematic search of the databases (PubMed, Embase, and Cochrane
      Library) was performed. Studies reporting on the association between obstructive
      sleep apnea and aortic dissection were included. Information on 424 cases of
      aortic dissection in 56,291 patients from one cohort, four case-controls, and two
      cross-sectional studies were included in this study. Results The summary
      suggested that patients with obstructive sleep apnea are associated with an
      overall significant 60% increase in the risk of aortic dissection, compared to
      unexposed patients (odds ratios 1.60; 95% confidence interval 1.01-2.53), with a
      significantly higher apnea-hypopnea index (mean difference 10.71; 95% confidence
      interval 7.46-13.96). Moreover, a greater relation was found between moderate-to
      severe obstructive sleep apnea and aortic dissection (odds ratios 4.43; 95%
      confidence interval 2.59-7.59). Adverse outcomes obtained by sleep study such as
      oxygen desaturation index (mean difference 10.51; 95% confidence interval 7.54
      13.48), average SaO2 (-1.36; 95% confidence interval -2.63 to -0.09), and minimum
      SaO2 (-3.63; 95% confidence interval -5.27 to -1.98) were correspondingly related
      to patients with aortic dissection. Conclusions Obstructive sleep apnea,
      especially moderate-to-severe obstructive sleep apnea, may impose an additional
      risk of suffering from aortic dissection with a potential mechanism including
      intermittent hypoxia.

PMID- 29566591
TI  - Malignant lymphoma with middle ear involvement in a Sprague-Dawley rat.
AB  - Sprague-Dawley rats are amongst the most widely used animals in biomedical
      research and malignant lymphoma has long been known to be a frequent neoplasm in
      these animals. A 9-month-old male control Sprague-Dawley rat from a toxicity
      study showed gelatinous material in the cranial cavity and dark, thickened
      cerebral meninges at necropsy. At microscopic evaluation of the temporal bone,
      neoplastic lymphocytes were seen invading several structures of the middle ear.
      The neoplastic cells appeared to extend from the marrow of the temporal bone,
      covered the dorsal part of the tympanic cavity wall, and surrounded and
      infiltrated the base of the tensor tympani muscle as well as the chorda tympani
      branch of the facial nerve. The lymphoma was generalized; neoplastic lymphocytes
      were also noted in numerous other tissues. Literature regarding neoplasms of the
      middle and inner ear in animals is scarce and, to our knowledge, this is the
      first report of a lymphoma involving the middle ear of a rat.

PMID- 29566590
TI  - The natural history of type 2 endoleaks after endovascular aneurysm repair
      justifies conservative management.
AB  - Objective Management of type 2 endoleaks after endovascular aneurysm repair has
      been controversial. Some advocate for conservative management, while others
      believe that intervention is indicated. This study investigated the natural
      history of type 2 endoleaks in order to derive direction in management. Methods
      Patients who had endovascular aneurysm repair at the Veterans Affairs Long Beach
      were retrospectively identified and computerized tomographic angiography was
      independently reviewed by a radiologist and a vascular surgeon. Type 2 endoleaks
      were analyzed for the following outcomes: rupture, duration of endoleak,
      spontaneous resolution, changes in the size of the aneurysm sac, and
      reintervention rates. Results Of the 160 patients who had completed required
      follow-up to date (mean 3 years) after endovascular aneurysm repair, 39 (24.4%)
      patients were identified as having a type 2 endoleak on computerized tomographic
      angiography imaging. 6 (15.4%) of these 39 patients required repair due to
      aneurysm sac growth >1 cm. 2 (5.13%) were repaired with an open procedure and 4
      (10.3%) with an endovascular approach. Of these 6 aneurysm leaks requiring
      repair, 4 (66.7%) had a simultaneous endoleak (types 1 or 3) in addition to the
      identified type 2 endoleak. Spontaneous resolution of type 2 endoleaks occurred
      in 16 (41.0%) patients. 4 patients (10.3%) had delayed type 2 endoleaks that
      presented 4, 9, 12, and 23 months after their 30 day post op computed tomography
      was normal. None of the 4 patients with delayed type 2 endoleaks required
      reintervention and none had aneurysm sac growth greater than 5 mm. Conclusions
      Overall, we found that 85% of patients who had type 2 endoleaks did not require
      intervention after a mean follow-up time of 3 years. The association of a type 1
      or 3 endoleak with a type 2 endoleak was more likely to require correction due to
      aneurysm expansion >1 cm, thus type 2 endoleaks associated with another type of
      endoleak require more aggressive management.

PMID- 29566592
TI  - Age-Friendly Communities and Life Satisfaction Among the Elderly in Urban China.
AB  - This study aims to examine the extent to which older adults' perceptions of
      environmental age-friendliness are associated with their life satisfaction. We
      used a national representative sample ( N = 9,965) with elders aged 60 and above
      from urban China and structural equation modeling to analyze the relationship
      among community characteristics, socioeconomic status (SES), and life
      satisfaction. Results showed that older people's perceptions of housing
      conditions, local amenities, and social inclusion were significantly associated
      with general life satisfaction. Multigroup comparison tests indicated that no
      disparities in the aforementioned relationships among SES subgroups. However, the
      socioeconomically disadvantaged elderly population was shown to have the lowest
      assessment of community age-friendliness. Findings emphasized the potential role
      of age-friendly communities as having an influential force on older adults'
      subjective well-being, regardless of their SES. Meanwhile, policy makers and
      practitioners should pay special attentions to improve the living environments of
      disadvantaged elders.

PMID- 29566593
TI  - Selective Vulnerability of the Foramen Magnum in a Rat Blast Traumatic Brain
      Injury Model.
AB  - Primary blast traumatic brain injury (bTBI) accounts for a significant proportion
      of wartime trauma. Previous studies have demonstrated direct brain injury by
      blast waves, but the effect of the location of the blast epicenter on the skull
      with regard to brain injury remains poorly characterized. In order to investigate
      the role of the blast epicenter location, we modified a previously established
      rodent model of cranium-only bTBI to evaluate two specific blast foci: a
      rostrally focused blast centered on bregma (B-bTBI), which excluded the foramen
      magnum region, and a caudally focused blast centered on the occipital crest,
      which included the foramen magnum region (FM-bTBI). At all blast overpressures
      studied (668-1880 kPa), rats subjected to FM-bTBI demonstrated strikingly higher
      mortality, increased durations of both apnea and hypoxia, and increased severity
      of convexity subdural hematomas, than rats subjected to B-bTBI. Together, these
      data suggest a unique role for the foramen magnum region in mortality and brain
      injury following blast exposure, and emphasize the importance of the choice of
      blast focus location in experimental models of bTBI.

PMID- 29566594
TI  - Coping as a Mediator Between Parental Attachment and Resilience: An Examination
      of Differential Effects Between Chinese Adolescents From Single Parent Families
      Versus Those From Intact Families.
AB  - The crude divorce rate has been increasing steadily for over a decade in China.
      Consequently, more and more children have to face the challenge of growing up in
      single parent families. The current study investigated the mediating effects of
      problem-oriented and emotion-oriented coping on the relationship between parental
      attachment and psychological resilience among a sample of Chinese adolescents
      from single parent families and intact families. Participants were 975 high
      school students (44.30% males; aged 15-19 years, M = 16.32 years, SD = 0.74), 871
      from intact families and 104 from single parent families. Structural equation
      modeling showed that security in maternal attachment was positively associated
      with resilience through the indirect effect of reduced emotion-oriented coping
      among adolescents from single parent families. Among adolescents from intact
      families, security in maternal attachment was both directly associated with
      resilience and indirectly through enhanced problem-oriented and reduced emotion
      oriented coping. Security in paternal attachment was associated with resilience
      both directly and indirectly through enhanced problem-oriented coping as well
      among those from intact families. Female adolescents exhibited significantly
      lower levels of resilience than male adolescents did regardless of the marital
      status of their parents. Limitations and suggestions for future research are
      discussed.

PMID- 29566595
TI  - 15-Year Secular Trends in Cognitive Function Among Older Adults in the United
      States.
AB  - Cognitive impairment is associated with various chronic diseases, including
      mobility limitation and early mortality. Thus, evaluating changes in cognition is
      of paramount public health interest. The purpose of this study was to evaluate
      secular trends in cognitive function among a representative sample of the U.S.
      older adult population. Data from the 1999-2000, 2001-2002, 2011-2012, and 2013
      2014 National Health and Nutrition Examination Survey were utilized to identify
      an aggregate sample of adults 60+ years of age. The sample size across the four
      respective cycles was 1417, 1558, 1422, and 1592. Three cognitive assessments
      were employed, including the CERAD Word Learning subset (Consortium to Establish
      a Registry for Alzheimer's disease), the Animal Fluency test, and the Digit
      Symbol Substitution Test (DSST). For the entire sample and several
      subpopulations, DSST scores increased from 1999 to 2012 and then decreased in the
      2013 to 2014 cycle. For all CERAD trials, there was evidence of increased CERAD
      performance from 2011-2012 to 2013-2014. No secular trends were observed for the
      Animal Fluency task across these cycles. Select cognitive parameters appear to be
      improving among U.S. older adults. Future work is needed to further explore
      secular trends in cognitive sustainability, and, as evidenced by our present
      study, cognitive enrichment over time.

PMID- 29566596
TI  - Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic
      Review From the Children's Oncology Group.
AB  - Peripheral neuropathy is a known side effect of several chemotherapy agents,
      including vinca alkaloids and platinum-based chemotherapy. Early recognition and
      monitoring of this side effect is an important role of the pediatric oncology
      nurse. There are a variety of peripheral neuropathy assessment tools currently in
      use, but the usefulness of these tools in identifying and grading neuropathy in
      children varies, and there is currently no standardized tool in place to evaluate
      peripheral neuropathy in pediatric oncology. A systematic review was performed to
      identify the peripheral neuropathy assessment tools that best evaluate the early
      onset and progression of peripheral neuropathy in pediatric patients receiving
      vincristine. Because of the limited information available in pediatric oncology,
      this review was extended to any pediatric patient with neuropathy. A total of 8
      studies were included in the evidence synthesis. Based on available evidence, the
      pediatric-modified Total Neuropathy Scale (ped-m TNS) and the Total Neuropathy
      Score-pediatric version (TNS-PV) are recommended for the assessment of
      vincristine-induced peripheral neuropathy in children 6 years of age and older.
      In addition, several studies demonstrated that subjective symptoms alone are not
      adequate to assess for vincristine-induced peripheral neuropathy. Nursing
      assessment of peripheral neuropathy should be an integral and regular part of
      patient care throughout the course of chemotherapy treatment.

PMID- 29566597
TI  - Depression in the First Year after Traumatic Brain Injury.
AB  - The aims of this study were to document the frequency of major and minor
      depressive episodes in the first year after traumatic brain injury (TBI), taking
      into account TBI severity and pre-morbid history of major depression, and to
      describe trajectories of depressive episodes. Participants were 227 adults who
      were hospitalized post-TBI (76% male; mean age = 41 years; 50% mild, 33%
      moderate, and 17% severe TBI). Major and minor depressive episodes were assessed
      with the Mini International Neuropsychiatric Interview at three time points (4,
      8, and 12 months after TBI). Overall, 29% of participants had a major depressive
      episode in at least one of the three assessments, with fairly stable rates across
      assessments. Participants with mild TBI were more likely than those with
      moderate/severe TBI to be diagnosed with major depression, as were individuals
      with a positive pre-morbid history of depression compared to those without such
      history. In addition, 13% of participants had a minor depressive episode in at
      least one of the three assessments. Rates of minor depression significantly
      decreased from 4 to 8-12 months post-injury. Results also revealed a wide variety
      of trajectories of depressive episodes across assessments. Of note, 52% of major
      depression cases still fulfilled diagnostic criteria 4 months later, whereas 38%
      of minor depression cases deteriorated to major depression at the following
      assessment. These findings suggest that depression is highly prevalent after TBI,
      and monitoring of patients with subthreshold depressive symptoms is warranted in
      order to prevent the development of full-blown major depressive episodes.

PMID- 29566598
TI  - Validation study of the Alzheimer's disease assessment scale-cognitive subscale
      (ADAS-Cog) for the Portuguese patients with mild cognitive impairment and
      Alzheimer's disease.
AB  - OBJECTIVE: The Alzheimer's disease assessment scale-Cognitive Subscale (ADAS-Cog)
      is a battery to assess cognitive performance in Alzheimer's disease (AD) and was
      developed according to the core characteristics of cognitive decline in AD:
      memory, language, praxis, constructive ability, and orientation. The aim of this
      study was to explore the diagnostic accuracy and discriminative capacity of the
      ADAS-Cog for Mild Cognitive Impairment (MCI) and AD, using cut-off points for the
      Portuguese population. METHOD: The European Portuguese version of the ADAS-Cog
      was administrated to 650 participants, divided into a control group (n = 210), an
      MCI group (n = 240), and an AD group (n = 200). The clinical groups fulfilled
      standard international diagnostic criteria. Controls were healthy cognitive
      participants actively integrated in the community. The neuropsychological
      assessment protocol included the ADAS-Cog, the Mini Mental State Examination
      (MMSE), the Montreal Cognitive Assessment (MoCA), and the Adults and Older Adults
      Functional Assessment Inventory (IAFAI). RESULTS: The ADAS-Cog revealed good
      psychometric indicators, and the total scores were significantly different
      between the three groups (p < .001: Control < MCI < AD). The optimal cut-off
      points established were: MCI > 9 points (AUC = .835; sensitivity = 58% and
      specificity = 91%) and AD > 12 points (AUC = .996; sensitivity = 94% and
      specificity = 98%). CONCLUSIONS: Our findings confirmed the capacity of the ADAS
      Cog total score to identify cognitive impairment in AD patients, with poor
      sensitivity for MCI, in a Portuguese cohort.

PMID- 29566599
TI  - Synergistic effects of rmhTRAIL and 17-AAG on the proliferation and apoptosis of
      multiple myeloma cells.
AB  - OBJECTIVE: This study aimed to investigate synergistic effects of recombinant
      mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL)
      and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 
      allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and
      apoptosis of multiple myeloma (MM) cells. METHODS: MTT assays evaluated
      inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and
      treatment durations on the proliferation of RPMI8226 and U266 cells. The half
      maximal inhibitory concentration was calculated using OriginPro7.5. Synergistic
      effects of rmhTRAIL and 17-AAG on apoptosis of MM cells were detected using flow
      cytometry at 24 and 48 h post-treatment. To evaluate synergistic effects of
      rmhTRAIL and 17-AAG, the Q-value was calculated using King's formula. RESULTS:
      rmhTRAIL exhibited significant inhibitory effects on the proliferation of
      RPMI8226 cells in a dose- and time-dependent manner (>50%), whereas U266 cells
      were not sensitive to rmhTRAIL (<50%). 17-AAG inhibited the proliferation of
      RPMI8226 and U266 cells in a dose-dependent manner (>80%). Significant
      synergistic effects of rmhTRAIL and 17-AAG on the proliferation of RPMI8226 cells
      were revealed (Q-value > 1.15), whereas synergistic effects were not evident on
      the proliferation of U266 cells (Q-value < 1.15). rmhTRAIL and 17-AAG exhibited
      significant synergistic effects on apoptosis of RPMI8226 and U266 cells (Q-value
      > 1.15). CONCLUSION: The combined application of rmhTRAIL and 17-AAG revealed
      favorable synergistic effects in the treatment of MM.

PMID- 29566600
TI  - Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of
      a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems
      National Database.
AB  - For patients surviving serious traumatic brain injury (TBI), families and other
      stakeholders often desire information on long-term functional prognosis, but
      accurate and easy-to-use clinical tools are lacking. We aimed to build
      utilitarian decision trees from commonly collected clinical variables to predict
      Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate
      to-severe closed TBI. Flexible classification tree statistical modeling was used
      on prospectively collected data from the TBI-Model Systems (TBIMS) inception
      cohort study. Enrollments occurred at 17 designated, or previously designated,
      TBIMS inpatient rehabilitation facilities. Analysis included all participants
      with nonpenetrating TBI injured between January 1997 and January 2017. Sample
      sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross
      sectional exclusions (death, vegetative state, insufficient post-injury time, and
      unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration
      consistently dominated branching hierarchy and was the lone injury characteristic
      significantly contributing to GOS predictability. Lower-order variables that
      added predictability were age, pre-morbid education, productivity, and
      occupational category. Generally, patient outcomes improved with shorter PTA,
      younger age, greater pre-morbid productivity, and higher pre-morbid vocational or
      educational achievement. Across all prognostic groups, the best and worst good
      recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe
      disability rates were 3.9% and 64.1%. Predictability in test data sets ranged
      from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to
      0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful
      tool to provide prognostic information on long-term functional outcomes for adult
      survivors of moderate and severe closed TBI. Predictive accuracy for GOS level
      was demonstrated in an independent test sample. Length of PTA, a clinical marker
      of injury severity, was by far the most critical outcome determinant.

PMID- 29566602
TI  - A Comparison of Intimate Partner Violence Strangulation Between Same-Sex and
      Different-Sex Couples.
AB  - Strangulation is a common and dangerous form of intimate partner violence (IPV).
      Nonfatal strangulation is a risk factor for homicide; can lead to severe, long
      term physical and mental health sequelae; and can be an effective strategy of
      coercion and control. To date, research has not examined strangulation within
      same-sex couples. The objective of this cross-sectional, observational research
      is to identify whether and to what extent the detection of strangulation and
      coercive control differs between same-sex and different-sex couples in police
      reports of IPV. Data ( n = 2,207) were obtained from a single police department
      in the southwest United States (2011-2013). Bivariate analyses examined
      differences in victim and offender demographics, victim injury, violence, and
      coercive controlling behaviors between same-sex (male-male and female-female) and
      different-sex couples (female victim-male offender). Logistic regression was used
      to examine associations between strangulation, victim and offender demographics,
      coercive controlling behaviors, and couple configuration. Strangulation was
      reported significantly more often in different-sex (9.8%) than in female and male
      same-sex couple cases (5.2% and 5.3%, respectively; p < .05). Injury, however,
      was reported more frequently in same-sex than in different-sex couples ( p <
      .05). Couple configuration ( p < .05), coercive control ( p < .05), and injury (
      p < .05) significantly predict strangulation. Findings suggest that nonfatal
      strangulation occurs within at least a minority of same-sex couples; it is
      possible that underdetection by law enforcement makes it appear less common than
      it actually is. Regardless of couple configuration, timely identification of
      strangulation and subsequent referral to medical and social service providers is
      essential for preventing repeated strangulation, life-threatening injury, and the
      long-term health effects of strangulation.

PMID- 29566603
TI  - Did I Help Get Us Here?

PMID- 29566601
TI  - Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal
      Cord Injury in Rat Model.
AB  - Although there has been a significant amount of research focused on the
      pathophysiology of spinal cord injury (SCI), there is limited information on the
      consequences of SCI on remote organs. SCI can produce significant effects on a
      variety of organ systems, including the gastrointestinal tract. Patients with SCI
      often suffer from severe, debilitating bowel dysfunction in addition to their
      physical disabilities, which is of major concern for these individuals because of
      the adverse impact on their quality of life. Herein, we report on our
      investigation into the effects of SCI and subsequent antibiotic treatment on the
      intestinal tissue and microbiota. For that, we used a thoracic SCI rat model and
      investigated changes to the microbiota, proinflammatory cytokine levels, and
      bacterial communication molecule levels post-injury and gentamicin treatment for
      7 days. We discovered significant changes, the most interesting being the
      differences in the gut microbiota beta diversity of 8-week SCI animals compared
      to control animals at the family, genus, and species level. Specifically, 35
      operational taxonomic units were enriched in the SCI animal group and three were
      identified at species level; Lactobacillus intestinalis, Clostridium disporicum,
      and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was
      identified as depleted in the SCI animal group. Proinflammatory cytokines
      interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor
      necrosis factor alpha were found to be significantly elevated in intestinal
      tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further,
      levels of IL-1beta, IL-12, and MIP-2 significantly correlated with changes in
      beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the
      early effects of SCI on the microbiota and gastrointestinal tract, highlighting
      the need for further investigation to elucidate the mechanism underlying these
      effects.

PMID- 29566604
TI  - Regenerative Medicine and Surgery in the Foot and Ankle Practice.

PMID- 29566606
TI  - Erratum.
AB  - Karimi MT. The Evaluation of Foot Rockers on the Kinematic Parameters of
      Individuals With Diabetes [published online ahead of print October 4, 2017]. Foot
      Ankle Surg. 2017. doi: 10.1177/1938640017729500 The above article was published
      OnlineFirst with the following errors which have now been corrected. On the first
      page, the author's details were incorrect. The correct details should read as
      below. Author Name - Mohammad Taghi Karimi, PhD Affiliations - Musculoskeletal
      Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
      Rehabilitation Sciences Research Center, Shiraz University of Medical Sciences,
      Shiraz Iran Under the 'Discussion' section, first para, the in-text citation of
      reference number 24 was missing. The correct sentence should read as below. Van
      Bogart et al (2009)24 also demonstrated that whereas the toe rocker reduced the
      range of motion of lower-extremity joints in the stance phase, it did not have an
      effect on spatiotemporal parameters. All the subsequent versions have been
      corrected.

PMID- 29566608
TI  - Coxiella burnetii in Infertile Dairy Cattle With Chronic Endometritis.
AB  - Coxiella burnetii is an obligate intracellular pathogen and the cause of Q fever
      in many animal species and humans. Several studies have reported the association
      between C. burnetii and abortion, premature delivery, stillbirth, and weak
      offspring. However, no solid evidence indicates that C. burnetii causes
      endometritis, subfertility, and retained fetal membranes. For this study,
      histopathological and PCR evaluation were performed on 40 uterine biopsies from
      dairy cattle with poor fertility. Uterine swabs were concurrently tested with
      microbiology assays. The endometrial biopsies of 30 cows did not have any
      significant lesions, and no pathogens were identified by aerobic bacterial
      culture and PCR. Ten cows were PCR-positive for C. burnetii and negative for
      other pathogens by aerobic bacterial culture and PCR. These 10 cases revealed a
      mild to severe chronic endometritis admixed with perivascular and periglandular
      fibrosis. Immunohistochemical evaluation of C. burnetii PCR-positive biopsies
      identified, for the first time, the presence of intralesional and
      intracytoplasmic C. burnetii in macrophages in the endometrium of cattle.

PMID- 29566609
TI  - DNA Methylation Status of the Estrogen Receptor alpha Gene in Canine Mammary
      Tumors.
AB  - Estrogen receptor alpha (ERalpha) has an important role in mammary
      carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the
      most aggressive tumors show loss of ERalpha expression, which in human breast
      cancer has been attributed to methylation of the cytosine followed by guanine
      (CpG) island within the estrogen receptor alpha gene ( ESR1) promoter. This study
      aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERalpha
      expression in canine mammary tumors. Twenty-one canine mammary samples were
      sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and
      normal gland (n = 4). Immunohistochemical analysis and reverse-transcription
      quantitative real-time PCR were performed to assess ERalpha expression and ESR1
      mRNA levels. The methylation status was determined using sodium-bisulfite-treated
      DNA sequencing. All normal mammary glands and benign tumors showed high ERalpha
      expression (score range, 5-8). Six of the nine malignant tumors did not show
      ERalpha expression (score 0), two had score 2, and one had score 4. Lower ERalpha
      ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary
      tumors than in the other two groups. Canine ESR1 has an intragenic and non
      promoter-associated CGI, different from humans. No significant variation in
      methylation percentage was observed among the groups, suggesting that ESR1 is not
      regulated by DNA methylation, unlike that in humans. This difference should be
      considered in further research using ERalpha as a biomarker for mammary tumors in
      canine studies on ERalpha-targeting therapy.

PMID- 29566610
TI  - Histologic Changes Associated With Placental Separation in Gilts Infected with
      Porcine Reproductive and Respiratory Syndrome Virus.
AB  - The placenta is a vital organ providing the developing fetus with nutrient and
      gas exchange, thermoregulation, and waste elimination necessary for fetal
      development, as well as producing hormones to maintain pregnancy. It is
      hypothesized that fetal pig death in porcine reproductive and respiratory
      syndrome may be attributed to pathology of the maternal-fetal interface leading
      to premature placental separation. This study was designed to evaluate the
      chronologic progression of porcine reproductive and respiratory syndrome virus
      (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on
      placental separation in experimentally challenged third-trimester gilts. Fifteen
      gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 +/-
      0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated
      control per time point were euthanized, and uterine and fetal placental tissues
      corresponding to each fetus were collected for histopathologic evaluation. The
      presence of any fetal lesion was 23 times more likely in compromised (meconium
      stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV
      infected gilts, endometritis was more severe than placentitis, and the severity
      of endometrial inflammation and vasculitis increased progressively from 2 to 14
      days postinoculation. Neither placental vasculitis nor a chronologic progression
      in the severity of placental detachment was observed. Severe placental detachment
      was more frequently present in PRRSV-infected compared with noninfected samples
      and was most significantly associated with placental inflammation, compared with
      other uterine lesions, viral load, or termination day. The results of this study
      suggest that placental separation by itself is not sufficient to significantly
      compromise fetal viability in reproductive porcine reproductive and respiratory
      syndrome.

PMID- 29566611
TI  - Treatment of HCV in the Department of Corrections in the Era of Oral Medications.
AB  - Chronic hepatitis C virus (HCV) is widely prevalent in the Virginia Department of
      Corrections (DOC). However, sustained virologic response (SVR) with all oral
      direct-acting antiviral (DAA) therapy is unknown. HCV treatment was provided
      through telemedicine following guidelines of the American Association for the
      Study of Liver Diseases and Infectious Diseases Society of America. SVR12 in the
      DOC was compared in two control groups: privately insured and indigent patients
      receiving care in HCV treatment clinics by the same providers during the same
      time period. Of 220 DOC patients, 180 were started on therapy (158 genotype [GT]
      1, 15 GT2, and 10 GT3). SVR12 data on GT1 patients who received
      ledipasvir/sofosbuvir with or without ribavirin (RBV) were 96%, similar to our
      indigent (95%) and private clinic (93%) patients despite differences in age,
      gender, treatment experience, FIB-4, and use of RBV. Multiple logistic regression
      of GT1 patients identified lower FIB-4 ( p = .008) and treatment clinic ( p =
      .01) as independent predictors of SVR12. HCV treatment in the DOC by telemedicine
      with DAA is not only feasible but has a very high SVR12 similar to published
      trials.

PMID- 29566614
TI  - Love and Responsibility: A New Understanding of Leadership.
AB  - The purpose of the study is to investigate the importance of substance for the
      disclosure of ontological evidence. The methodology is inspired by Gadamer's
      hermeneutic philosophy and involves clinical application research using a
      deductive approach. This means that leaders in a clinical context were taught and
      participated in a discussion about a theoretical model of leadership with caring
      science and ontological substance. The result shows that the leaders' attention
      and focus were primarily directed toward administration, finances, and outer
      structures. Caring science and ontological substance contributed toward
      disclosing ontological evidence, and leadership emerged as caring, love, inner
      responsibility, guilt, and vulnerability. In this study, substance has been
      combined with teaching and group discussion as a methodical approach. Substance
      is the guiding issue and has been shown to lead to truth. The method is in a true
      sense nothing without substance.

PMID- 29566615
TI  - Hidden Figures: A Humanbecoming Movie Review.

PMID- 29566616
TI  - Toward Understanding Through Hermeneutic Letterwriting.
AB  - The authors present letterwriting as a hermeneutic research method in that it
      contributes to the methodological development within the hermeneutical research
      tradition in caring science. The hermeneutic methodology is inspired by Hans
      Georg Gadamer. Hermeneutic letterwriting in accordance with Gadamer's thought is
      a form of dialogue in writing, where what is truthful about the thing itself is
      unveiled with the help of the language. Hermeneutic letterwriting is presented in
      five steps. As a method, hermeneutic letterwriting is appropriate for complex
      caring science issues, and it offers new opportunities for attaining a deeper
      understanding of the world of caring.

PMID- 29566617
TI  - The Times They ARE A-Changing.

PMID- 29566618
TI  - Understanding the Essence of Caring from the Lived Experiences of Filipino
      Informatics Nurses.
AB  - Caring is considered a unique concept in nursing because it subsumes all
      intrinsic attributes of nursing as a human helping discipline. Scholars have
      argued that caring is usually seen as an encounter between nurses and patients,
      but how about nurses with minimal or absent nurse-patient encounters, like
      informatics nurses? In this study, we explored the meaning of the phenomenon of
      caring to present lived experiences of caring, namely caring as actions of coming
      in between; caring as expressed within embodied relations; and caring and the
      path traversed by informatics nurses. The informatics nurse-cyborg-patient triad
      speaks of Filipino informatics nurses' insightful understanding of the phenomenon
      of caring.

PMID- 29566619
TI  - The Humanbecoming Concept Inventing Model: A Reprise and More.

PMID- 29566620
TI  - Transformative Research: A New Frontier for Nursing?
AB  - In this column, the definition of transformational research is explored followed
      by a discussion of mixed methods as the preferred process for those who conduct
      such studies. Finally, there is consideration of why transformational research
      may be useful and a natural approach for the specific concerns of the profession
      of nursing.

PMID- 29566621
TI  - The Living Experience of Suffering: A Parse Method Study.
AB  - The purpose of this study was to investigate the humanuniverse living experience
      of suffering. The Parse method was used to answer the question: What is the
      structure of the living experience of suffering? The participants were 10 adults
      living in the community. The finding of the study, the structure of the living
      experience of suffering, was found to be as follows: Suffering is anguishing
      desolation with varied alliances arising with envisioning anew. The living
      experience of suffering is discussed in relation to the principles of the
      humanbecoming paradigm and in relation to further research inquiries.

PMID- 29566612
TI  - Defeating Cancers' Adaptive Defensive Strategies Using Thermal Therapies:
      Examining Cancer's Therapeutic Resistance, Ablative, and Computational Modeling
      Strategies as a means for Improving Therapeutic Outcome.
AB  - BACKGROUND: Diverse thermal ablative therapies are currently in use for the
      treatment of cancer. Commonly applied with the intent to cure, these ablative
      therapies are providing promising success rates similar to and often exceeding
      "gold standard" approaches. Cancer-curing prospects may be enhanced by deeper
      understanding of thermal effects on cancer cells and the hosting tissue,
      including the molecular mechanisms of cancer cell mutations, which enable
      resistance to therapy. Furthermore, thermal ablative therapies may benefit from
      recent developments in computer hardware and computation tools for planning,
      monitoring, visualization, and education. METHODS: Recent discoveries in cancer
      cell resistance to destruction by apoptosis, autophagy, and necrosis are now
      providing an understanding of the strategies used by cancer cells to avoid
      destruction by immunologic surveillance. Further, these discoveries are now
      providing insight into the success of the diverse types of ablative therapies
      utilized in the clinical arena today and into how they directly and indirectly
      overcome many of the cancers' defensive strategies. Additionally, the manner in
      which minimally invasive thermal therapy is enabled by imaging, which facilitates
      anatomical features reconstruction, insertion guidance of thermal probes, and
      strategic placement of thermal sensors, plays a critical role in the delivery of
      effective ablative treatment. RESULTS: The thermal techniques discussed include
      radiofrequency, microwave, high-intensity focused ultrasound, laser, and
      cryosurgery. Also discussed is the development of thermal adjunctive therapies
      the combination of drug and thermal treatments-which provide new and more
      effective combinatorial physical and molecular-based approaches for treating
      various cancers. Finally, advanced computational and planning tools are also
      discussed. CONCLUSION: This review lays out the various molecular adaptive
      mechanisms-the hallmarks of cancer-responsible for therapeutic resistance, on one
      hand, and how various ablative therapies, including both heating- and freezing
      based strategies, overcome many of cancer's defenses, on the other hand, thereby
      enhancing the potential for curative approaches for various cancers.

PMID- 29566622
TI  - Leading-Following: Guiding Care in the Community.
AB  - There are many ways nurses may be leaders and serve others in the community by
      utilizing a unique knowledge base that is grounded in the extant nursing theories
      and models. Leading and serving others with nursing knowledge demarks the
      contributions nurses make in all situations. The purpose of this paper is to
      illuminate how Parse's leading-following model and the Rainbow PRISM model (RPM)
      guide healthcare services in academic nursing health and wellness centers that
      serve the needs of all persons living in the community. Also, concepts within the
      RPM are discussed to align with Parse's current refinements of the humanbecoming
      paradigm.

PMID- 29566623
TI  - Understanding Childhood Perspectives.
AB  - Childhood should be a carefree and happy time. Some children, however, experience
      feelings of sadness, depression, anxiety, and other behavioral and mental health
      conditions. Healthcare providers need to develop a keen eye and an understanding
      demeanor to aid children and identify their needs and concerns. By providing a
      warm, inviting area for children to express their feelings and being with them in
      true presence, children may be more forthcoming in providing information about
      what they value.

PMID- 29566624
TI  - Interprofessional Education: Collaboration or Disciplinary Muddling?

PMID- 29566625
TI  - Respect: An Integrative Review.
AB  - Feeling respected is a universal human experience. The notion of respect is
      ubiquitous and discussed at varying levels of discourse. An integrative review of
      the literature on the phenomenon of respect is discussed. Literature was reviewed
      from the disciplines of philosophy, psychology, sociology, business, theology,
      and nursing. Three themes emerged from this literature review: respect honors
      inherent worth, respect intentionally co-shapes identity, and respect emerges
      with earned admiration.

PMID- 29566626
TI  - Holistic Leadership-Nursing's Unique Contribution to Healthcare.
AB  - This dialogue is focused on holistic leadership from the perspective of a well
      known leader in nursing. He frames the changing healthcare environment and
      nursing's unique contribution on the interprofessional team.

PMID- 29566627
TI  - The Fundamentality of Nursing Science.

PMID- 29566628
TI  - Nursing Science, Nursing Theory: Nurse Atheists, Nurse Agnostics, Nurse Theists.

PMID- 29566629
TI  - Transforming Ethical Thinking With Healthcare Reform: A Nursing Theoretical
      Perspective.
AB  - Healthcare reform discussions dominate the global media and legislative
      priorities. Many ethical straight-thinking questions arise over what the role of
      healthcare professionals, including nurses, should be in this debate. This
      article begins a discussion of potential ethical questions surrounding healthcare
      reform in light of a nursing theoretical humanbecoming community change model
      perspective.

PMID- 29566630
TI  - Toward Becoming a Global Nurse.
AB  - Globalization is a fact of modern life and healthcare that comes with various
      challenges and opportunities. After telling the story of one nurse's experience
      of working with Healthy Kids, Brighter Future in Zambia, the authors of this
      paper discuss five elements of being a global nurse. The five elements are
      global: aesthetics, intelligence, ethics, politics, and health. Implications for
      nursing and nursing education are also discussed.

PMID- 29566631
TI  - Thoughts About Nursing Curricula: Dark Clouds and Bright Lights.
AB  - In this essay, several nurse scholars who are particularly concerned about the
      contemporary state of nursing science present their concerns about the inclusion
      of nursing conceptual models and theories in the curricula of nursing programs
      (dark clouds) and ways in which the concerns have been addressed (bright lights).
      This essay is the second of two essays that were catalyzed by Barrett's paper,
      "Again, What Is Nursing Science?" The first essay was published in the previous
      issue of Nursing Science Quarterly.

PMID- 29566632
TI  - Transformation in Teaching-Learning: Emerging Possibilities with
      Interprofessional Education.
AB  - As the global community continues to face increasing mobility, rising healthcare
      costs, and decreasing or inaccessible healthcare resources, healthcare providers
      must be able to work together effectively in addressing the needs of
      progressively older and diverse persons and populations. In this column, the
      notion of interprofessional education (IPE) is explored and a model proposed for
      implementation in an institution offering graduate programs in nursing and
      occupational therapy. While the proposed model was developed for two disciplinary
      programs in a specific institution, the recommendations offered may easily be
      adapted for use in academic institutions offering varied and unique healthcare
      professional programs.

PMID- 29566633
TI  - Shame on You.
AB  - The following story is an introduction to an interesting exploration of the
      concept of shame, providing new insights into this important notion through the
      humanbecoming theoretical process of concept inventing.

PMID- 29566634
TI  - Concept Inventing: A Humanbecoming Perspective on Feeling Ashamed.
AB  - The author in this manuscript presents a humanbecoming concept inventing of
      feeling ashamed. It includes a literature review across several disciplines, an
      exploration of various art forms, discussions with others, and thoughtful
      contemplation that brings together a creative synthetic definition of feeling
      ashamed.

PMID- 29566635
TI  - 2017 Reviewer Thank You.

PMID- 29566636
TI  - An automated approach to classification of duplex assay for digital droplet PCR.
AB  - In the digital polymerase chain reaction (dPCR) detection process, discriminating
      positive droplets from negative ones directly affects the final concentration and
      is one of the most important factors affecting accuracy. Current automated
      classification methods usually discuss single-channel detections, whereas duplex
      detection experiments are less discussed. In this paper, we designed a
      classification method by estimating the upper limit of the negative droplets. The
      right tail of the negative droplets is approximated using a generalized Pareto
      distribution. Furthermore, our method takes fluorescence compensation in duplex
      assays into account. We also demonstrate the method on Bio-Rad's mutant detection
      dataset. Experimental results show that the method provides similar or better
      accuracy than other algorithms reported over a wider dynamic range.

PMID- 29566637
TI  - Integrating virtual screening and biochemical experimental approach to identify
      potential anti-cancer agents from drug databank.
AB  - Chemical libraries constitute a reservoir of pharmacophoric molecules to identify
      potent anti-cancer agents. Virtual screening of heterocyclic compound library in
      conjugation with the agonist-competition assay, toxicity-carcinogenicity
      analysis, and string-based structural searches enabled us to identify several
      drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a
      target. Molecular modeling study indicates that Cinnarizine fits well within the
      PKC C2 domain and exhibits extensive interaction with the protein residues.
      Molecular dynamics simulation of PKC-Cinnarizine complex at different
      temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that
      Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug
      Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula:
      see text]M. The breast cancer cells stimulated with Cinnarizine causes
      translocation of PKC-[Formula: see text] to the plasma membrane as revealed by
      immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently
      reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an
      IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL,
      respectively. It is due to the disturbance of cell cycle of breast cancer cells
      with reduction of S-phase and accumulation of cells in G1-phase. It disturbs
      mitochondrial membrane potentials to release cytochrome C into the cytosol and
      activates caspase-3 to induce apoptosis in cancer cells. The cell death was due
      to induction of apoptosis involving mitochondrial pathway. Hence, the current
      study has assigned an additional role to Cinnarizine as an activator of PKC and
      potentials of the approach to identify new molecules for anti-cancer therapy.
      Thus, in silico screening along with biochemical experimentation is a robust
      approach to assign additional roles to the drugs present in the databank for anti
      cancer therapy.

PMID- 29566638
TI  - GI-Cluster: Detecting genomic islands via consensus clustering on multiple
      features.
AB  - The accurate detection of genomic islands (GIs) in microbial genomes is important
      for both evolutionary study and medical research, because GIs may promote genome
      evolution and contain genes involved in pathogenesis. Various computational
      methods have been developed to predict GIs over the years. However, most of them
      cannot make full use of GI-associated features to achieve desirable performance.
      Additionally, many methods cannot be directly applied to newly sequenced genomes.
      We develop a new method called GI-Cluster, which provides an effective way to
      integrate multiple GI-related features via consensus clustering. GI-Cluster does
      not require training datasets or existing genome annotations, but it can still
      achieve comparable or better performance than supervised learning methods in
      comprehensive evaluations. Moreover, GI-Cluster is widely applicable, either to
      complete and incomplete genomes or to initial GI predictions from other programs.
      GI-Cluster also provides plots to visualize the distribution of predicted GIs and
      related features. GI-Cluster is available at https://github.com/icelu/GI_Cluster.

PMID- 29566639
TI  - Integrative analysis of gene expression and DNA methylation using unsupervised
      feature extraction for detecting candidate cancer biomarkers.
AB  - Currently, cancer biomarker discovery is one of the important research topics
      worldwide. In particular, detecting significant genes related to cancer is an
      important task for early diagnosis and treatment of cancer. Conventional studies
      mostly focus on genes that are differentially expressed in different states of
      cancer; however, noise in gene expression datasets and insufficient information
      in limited datasets impede precise analysis of novel candidate biomarkers. In
      this study, we propose an integrative analysis of gene expression and DNA
      methylation using normalization and unsupervised feature extractions to identify
      candidate biomarkers of cancer using renal cell carcinoma RNA-seq datasets. Gene
      expression and DNA methylation datasets are normalized by Box-Cox transformation
      and integrated into a one-dimensional dataset that retains the major
      characteristics of the original datasets by unsupervised feature extraction
      methods, and differentially expressed genes are selected from the integrated
      dataset. Use of the integrated dataset demonstrated improved performance as
      compared with conventional approaches that utilize gene expression or DNA
      methylation datasets alone. Validation based on the literature showed that a
      considerable number of top-ranked genes from the integrated dataset have known
      relationships with cancer, implying that novel candidate biomarkers can also be
      acquired from the proposed analysis method. Furthermore, we expect that the
      proposed method can be expanded for applications involving various types of multi
      omics datasets.

PMID- 29566640
TI  - Principal component analysis in protein tertiary structure prediction.
AB  - We discuss applicability of principal component analysis (PCA) for protein
      tertiary structure prediction from amino acid sequence. The algorithm presented
      in this paper belongs to the category of protein refinement models and involves
      establishing a low-dimensional space where the sampling (and optimization) is
      carried out via particle swarm optimizer (PSO). The reduced space is found via
      PCA performed for a set of low-energy protein models previously found using
      different optimization techniques. A high frequency term is added into this
      expansion by projecting the best decoy into the PCA basis set and calculating the
      residual model. This term is aimed at providing high frequency details in the
      energy optimization. The goal of this research is to analyze how the
      dimensionality reduction affects the prediction capability of the PSO procedure.
      For that purpose, different proteins from the Critical Assessment of Techniques
      for Protein Structure Prediction experiments were modeled. In all the cases, both
      the energy of the best decoy and the distance to the native structure have
      decreased. Our analysis also shows how the predicted backbone structure of native
      conformation and of alternative low energy states varies with respect to the PCA
      dimensionality. Generally speaking, the reconstruction can be successfully
      achieved with 10 principal components and the high frequency term. We also
      provide a computational analysis of protein energy landscape for the inverse
      problem of reconstructing structure from the reduced number of principal
      components, showing that the dimensionality reduction alleviates the ill-posed
      character of this high-dimensional energy optimization problem. The procedure
      explained in this paper is very fast and allows testing different PCA expansions.
      Our results show that PSO improves the energy of the best decoy used in the PCA
      when the adequate number of PCA terms is considered.

PMID- 29566641
TI  - Imagining the Future in Children with Severe Traumatic Brain Injury.
AB  - Imagining future events is thought to rely on recombination and integration of
      past episodic memory traces into future events. Future and past events contain
      episodic and nonepisodic details. Children with severe traumatic brain injury
      (TBI) were found to have impaired recall of past episodic (but not semantic)
      event details. Here, we examined whether severe TBI impairs construction of
      future events. Children with severe TBI (n = 15) and healthy controls (NC; n =
      33) 1) completed tests of anterograde (narrative and relational) memory and
      executive skills, 2) recalled past events and generated future events, and 3)
      rated events' phenomenological qualities. Events were scored for episodic
      (internal) and semantic (external) details. The groups did not differ in
      generating details of future events, although children with TBI recalled
      significantly fewer past internal (but not external) events' details relative to
      NCs. Moreover, the number of past internal details relative to future internal
      details was significantly higher in the NC group, but not in the TBI groups.
      Significant correlations between past and future were found for 1) internal
      details in both groups and 2) external details in the NC group. The TBI group
      rated their events as being less significant than did the NC group. The groups
      did not differ on ratings of visual intensity and rehearsal. Our study has shown
      that children who have sustained severe TBI had impoverished recall of past, but
      not generation of future, events. This unexpected dissociation between past and
      future event construction requires further research.

PMID- 29566642
TI  - The Ongoing U.S. Health Care Crisis: A Data Update.
AB  - While efforts to repeal the Affordable Care Act were narrowly defeated, grave
      problems in health care persist. Twenty-eight million remain uninsured, a number
      that is likely to increase. Millions more who have coverage cannot afford care
      because of high cost-sharing requirements. Meanwhile, the corporate takeover of
      medical care in the United States is at a gallop. This article provides a brief
      precis of recent data on U.S. health policy.

PMID- 29566643
TI  - Genomic selection signatures in sheep from the Western Pyrenees.
AB  - BACKGROUND: The current large spectrum of sheep phenotypic diversity results from
      the combined product of sheep selection for different production traits such as
      wool, milk and meat, and its natural adaptation to new environments. In this
      study, we scanned the genome of 25 Sasi Ardi and 75 Latxa sheep from the Western
      Pyrenees for three types of regions under selection: (1) regions underlying local
      adaptation of Sasi Ardi semi-feral sheep, (2) regions related to a long
      traditional dairy selection pressure in Latxa sheep, and (3) regions experiencing
      the specific effect of the modern genetic improvement program established for the
      Latxa breed during the last three decades. RESULTS: Thirty-two selected candidate
      regions including 147 annotated genes were detected by using three statistical
      parameters: pooled heterozygosity H, Tajima's D, and Wright's fixation index Fst.
      For Sasi Ardi sheep, chromosomes Ovis aries (OAR)4, 6, and 22 showed the
      strongest signals and harbored several candidate genes related to energy
      metabolism and morphology (BBS9, ELOVL3 and LDB1), immunity (NFKB2), and
      reproduction (H2AFZ). The major genomic difference between Sasi Ardi and Latxa
      sheep was on OAR6, which is known to affect milk production, with highly selected
      regions around the ABCG2, SPP1, LAP3, NCAPG, LCORL, and MEPE genes in Latxa
      sheep. The effect of the modern genetic improvement program on Latxa sheep was
      also evident on OAR15, on which several olfactory genes are located. We also
      detected several genes involved in reproduction such as ESR1 and ZNF366 that were
      affected by this selection program. CONCLUSIONS: Natural and artificial selection
      have shaped the genome of both Sasi Ardi and Latxa sheep. Our results suggest
      that Sasi Ardi traits related to energy metabolism, morphological, reproductive,
      and immunological features have been under positive selection to adapt this semi
      feral sheep to its particular environment. The highly selected Latxa sheep for
      dairy production showed clear signatures of selection in genomic regions related
      to milk production. Furthermore, our data indicate that the selection criteria
      applied in the modern genetic improvement program affect immunity and
      reproduction traits.

PMID- 29566644
TI  - The characteristics of ctDNA reveal the high complexity in matching the
      corresponding tumor tissues.
AB  - BACKGROUND: Next-generation sequencing (NGS) is an efficient and sensitive method
      to detect mutations from ctDNA. Many features and clinical conditions could
      significantly affect the concordance between ctDNA and corresponding tumor
      tissues. Our goal was to systematically investigate the critical factors
      contributing to different concordance between ctDNA and corresponding tumor
      tissues. METHODS: We recruited two groups of IIIB or IV lung cancer patients: The
      standard group to evaluate the accuracy of our method and the concordance between
      ctDNA and tumor tissues, and the study group with various clinical conditions. We
      applied our unique identification (UID) indexed capturing-based sequencing (UC
      Seq) to ctDNA samples, and confirm the results by Droplet digital PCR (ddPCR).
      RESULTS: Considering mutations detected from NGS of tumor tissues as golden
      standard, UC-Seq achieved overall 93.6% sensitivity for SNVs and Indels, and 0.8
      Pearson correlation between tumor TMB and bTMB. Efficacious treatments, long
      sampling date (more than 2 weeks) between tumor tissues and ctDNA and low
      concentrations of cfDNA (less than 9 ng/ml) could significantly decrease the
      concordance between ctDNA and tumor tissues. About 84% mutations showed shorter
      mutant fragment length than that of wild-type fragments, and the AFs of mutations
      could be significantly enriched in small-size ctDNA. CONCLUSIONS: In late-stage
      lung cancer patients, ctDNA generally has high concordance with tumor tissues.
      However it could be significantly affected by three clinical conditions which
      could dynamically change the content of ctDNA. Moreover, the detection limit
      could be further extended by enriching small-size ctDNA in the preparation of
      samples.

PMID- 29566645
TI  - Oscillatory motor patterning is impaired in neurofibromatosis type 1: a
      behavioural, EEG and fMRI study.
AB  - BACKGROUND: Neurofibromatosis type1 (NF1) is associated with a broad range of
      behavioural deficits, and an imbalance between excitatory and inhibitory
      neurotransmission has been postulated in this disorder. Inhibition is involved in
      the control of frequency and stability of motor rhythms. Therefore, we aimed to
      explore the link between behavioural motor control, brain rhythms and brain
      activity, as assessed by EEG and fMRI in NF1. METHODS: We studied a cohort of 21
      participants with NF1 and 20 age- and gender-matched healthy controls, with a
      finger-tapping task requiring pacing at distinct frequencies during EEG and fMRI
      scans. RESULTS: We found that task performance was significantly different
      between NF1 and controls, the latter showing higher tapping time precision. The
      time-frequency patterns at the beta sub-band (20-26 Hz) mirrored the behavioural
      modulations, with similar cyclic synchronization/desynchronization patterns for
      both groups. fMRI results showed a higher recruitment of the extrapyramidal motor
      system (putamen, cerebellum and red nucleus) in the control group during the
      fastest pacing condition. CONCLUSIONS: The present study demonstrated impaired
      precision in rhythmic pacing behaviour in NF1 as compared with controls. We found
      a decreased recruitment of the cerebellum, a structure where inhibitory
      interneurons are essential regulators of rhythmic synchronization, and in deep
      brain regions pivotally involved in motor pacing. Our findings shed light into
      the neural underpinnings of motor timing deficits in NF1.

PMID- 29566646
TI  - Early and late feathering in turkey and chicken: same gene but different
      mutations.
AB  - BACKGROUND: Sex-linked slow (SF) and fast (FF) feathering rates at hatch have
      been widely used in poultry breeding for autosexing at hatch. In chicken, the sex
      linked K (SF) and k+ (FF) alleles are responsible for the feathering rate
      phenotype. Allele K is dominant and a partial duplication of the prolactin
      receptor gene has been identified as the causal mutation. Interestingly, some
      domesticated turkey lines exhibit similar slow- and fast-feathering phenotypes,
      but the underlying genetic components and causal mutation have never been
      investigated. In this study, our aim was to investigate the molecular basis of
      feathering rate at hatch in domestic turkey. RESULTS: We performed a sequence
      based case-control association study and detected a genomic region on chromosome
      Z, which is statistically associated with rate of feathering at hatch in turkey.
      We identified a 5-bp frameshift deletion in the prolactin receptor (PRLR) gene
      that is responsible for slow feathering at hatch. All female cases (SF turkeys)
      were hemizygous for this deletion, while 188 controls (FF turkeys) were
      hemizygous or homozygous for the reference allele. This frameshift mutation
      introduces a premature stop codon and six novel amino acids (AA), which results
      in a truncated PRLR protein that lacks 98 C-terminal AA. CONCLUSIONS: We present
      the causal mutation for feathering rate in turkey that causes a partial C
      terminal loss of the prolactin receptor, and this truncated PRLR protein is
      strikingly similar to the protein encoded by the slow feathering K allele in
      chicken.

PMID- 29566647
TI  - Balanced selection on purebred and crossbred performance increases gain in
      crossbreds.
AB  - BACKGROUND: Genomic selection can be applied to select purebreds for crossbred
      performance (CP). The average performance of crossbreds can be considered as the
      summation of two components, i.e. the breed average (BA) of the parental breeds
      and heterosis (H) present in crossbreds. Selection of pure breeds for CP based on
      genomic estimated breeding values for crossbred performance (GEBV-C) or for
      purebred performance (GEBV-P) may differ in their ability to exploit BA and H and
      can affect the merit of crossbreds in both the short and long term. Selection
      based on GEBV-C is beneficial for CP, because H in crossbreds is efficiently
      exploited, whereas selection on GEBV-P results in more genetic progress in pure
      breeds, which increases the BA component of CP. To investigate the outcome of
      selection on GEBV-C and GEBV-P in both the short and long term, a two-way
      crossbreeding program was simulated to test the following hypotheses: (1) does
      selection on GEBV-P result in higher long-term CP compared to selection on GEBV-C
      and (2) does selection on a combination of GEBV-P and GEBV-C lead to more long
      term gain in CP than selection on either separately. METHODS: We investigated the
      performance of crossbreds in a two-way crossbreeding program across 40
      generations and considered different criteria to select purebred parents that
      ranged from selection on purebred performance to selection for CP with different
      weights on genomic evaluations based on purebred and CP. These criteria were
      compared under three genetic models to investigate the effects of the amount of
      dominance variance, absence of over-dominance, and the structure of the reference
      population on CP, both in the short and long term. RESULTS AND CONCLUSIONS:
      Although beneficial in the short to medium term, genomic selection in pure breeds
      on a criterion that specifically targets CP was inferior to selection for
      purebred performance in the long term. A selection criterion that maximizes a
      combination of short- and long-term responses in CP, should improve the
      components that define crossbred merit (i.e., BA and H) simultaneously.

PMID- 29566648
TI  - Estimating the health consequences of flight attendant work: comparing flight
      attendant health to the general population in a cross-sectional study.
AB  - BACKGROUND: Flight attendants are an understudied occupational group, despite
      undergoing a wide and unique range of adverse job-related exposures. In our
      study, we aimed to characterize the health profile of cabin crew relative to the
      U.S. general population. METHODS: In 2014-2015, we surveyed participants of the
      Harvard Flight Attendant Health Study. We compared the prevalence of their health
      conditions to a contemporaneous cohort in the National Health and Nutrition
      Examination Survey (NHANES 2013-2014) using age-weighted standardized prevalence
      ratios (SPRs). We also analyzed associations between job tenure and selected
      health outcomes, using logistic regression and adjusting for potential
      confounders. RESULTS: Compared to the NHANES population (n = 2729), flight
      attendants (n = 5366) had a higher prevalence of female reproductive cancers (SPR
      = 1.66, 95% CI: 1.18-2.33), cancers at all sites (SPR = 2.15, 95% CI: 1.73-2.67
      among females), as well as sleep disorders, fatigue, and depression, with SPRs
      ranging between 1.98 and 5.57 depending on gender and the specific condition
      examined. In contrast, we observed a decreased prevalence of cardiac and
      respiratory outcomes among flight crew relative to NHANES. Health conditions that
      increased with longer job tenure were sleep disorders, anxiety/depression,
      alcohol abuse, any cancer, peripheral artery disease, sinusitis, foot surgery,
      infertility, and several perinatal outcomes. CONCLUSIONS: We observed higher
      rates of specific adverse health outcomes in U.S. flight attendants compared to
      the general population, as well as associations between longer tenure and health
      conditions, which should be interpreted in light of recall bias and a cross
      sectional design. Future longitudinal studies should evaluate specific exposure
      disease associations among flight crew.

PMID- 29566649
TI  - Contextualising health screening risk assessments in police custody suites -
      qualitative evaluation from the HELP-PC study in London, UK.
AB  - BACKGROUND: In the UK, police custody officers have a responsibility to screen
      for health morbidity and vulnerability among detainees. This study aimed to
      develop an understanding of the barriers to performing effective health screening
      in police custody suites, understand the impact of screening tools on practice
      within the custody suite, and to identify factors that could hinder or facilitate
      the future implementation of a new screening intervention in this environment.
      METHODS: A qualitative study was conducted alongside a quantitative evaluation of
      a novel screening tool. Qualitative methods included observation of the custody
      environment, semi-structured interviews with police staff, and elicitation of
      comments from detainees about their experiences of screening. Data were analysed
      inductively using thematic analysis. Normalization Process Theory (NPT) was used
      to inform data collection and as a framework for higher level analysis of
      findings. RESULTS: Five overall constructs were identified that develop
      understanding of the integration of health screening within custody: the
      workability of risk assessment screening tools; the effect of the custody
      environment and the people therein; shifts in professional roles and
      interrelationships amongst staff; cultural responses to risk and liability in
      police work; how infrastructure, knowledge and skills can impact on detainee
      safety. CONCLUSIONS: Health and risk assessment screening in police custody is a
      complex and demanding activity which extends beyond the delivery of a screening
      tool. Professional roles, the demanding environment and police culture impact on
      the overall process. Recommendations for improved integration of health and risk
      assessment screening in wider police custody practice are proposed.

PMID- 29566650
TI  - Short-term changes of choroidal vascular structures after phacoemulsification
      surgery.
AB  - BACKGROUND: To evaluate the changes of choroidal vascular structures in patients
      after phacoemulsification surgery. METHODS: A self-control study was conducted on
      36 eyes of 36 patients who had uneventful phacoemulsification. Choroidal images
      were acquired preoperatively, 7 days (D7), 1 month (M1), and 3 months (M3) after
      surgery from enhanced depth imaging (EDI) optical coherence tomography (OCT)
      scans. Choroidal vascularity index (CVI) was used to assess vascular status of
      the choroid using image binarization by the Niblack method. The postoperative
      values of mean CVI were compared with baseline by paired t-test. Univariate and
      multiple linear regression analyses were performed to determine the associations
      between CVI and other factors. RESULTS: The mean age of the recruited patients
      was 63.1 +/- 6.9 years. The mean CVI at baseline was 60.1 +/- 5.5%. After
      surgery, the CVI significantly increased to 61.7 +/- 5.3% at D7, 63.6 +/- 4.4% at
      M1 and 64.8 +/- 4.0% at M3 (p = 0.035, 0.0006, < 0.0001, respectively).
      Univariate and multiple regression analysis revealed a positive association
      between CVI and subfoveal choroidal thickness (SFCT) at pre-operation and no
      significant association with age, axial length (AL), intraocular pressure (IOP)
      and gender at all timepoints. CONCLUSIONS: Phacoemulsification induced increased
      CVI in patients diagnosed with cataract. Evaluation of the long-term change of
      CVI following surgery may provide valuable information for studying the
      relationship between phacoemulsification and disorders of the choroid.

PMID- 29566651
TI  - Complementary surveillance strategies are needed to better characterise the
      epidemiology, care pathways and treatment outcomes of tuberculosis in children.
AB  - BACKGROUND: Tuberculosis (TB) in young and HIV-infected children is frequently
      diagnosed at hospital level. In settings where general hospitals do not function
      as TB reporting units, the burden and severity of childhood TB may not be
      accurately reflected in routine TB surveillance data. Given the paucibacillary
      nature of childhood TB, microbiological surveillance alone will miss the majority
      of hospital-managed children. The study objective was to combine complementary
      hospital-based surveillance strategies to accurately report the burden, spectrum
      and outcomes of childhood TB managed at referral hospital-level in a high TB
      burden setting. METHODS: We conducted a prospective cohort study including all
      children (< 13 years) managed for TB at a large referral hospital in Cape Town,
      South Africa during 2012. Children were identified through newly implemented
      clinical surveillance in addition to existing laboratory surveillance. Data were
      collected from clinical patient records, the National Health Laboratory Service
      database, and provincial electronic TB registers. Descriptive statistics were
      used to report overall TB disease burden, spectrum, care pathways and treatment
      outcomes. Univariate analysis compared characteristics between children
      identified through the two hospital-based surveillance strategies to characterise
      the group of children missed by existing laboratory surveillance. RESULTS: During
      2012, 395 children (180 [45.6%] < 2 years) were managed for TB. Clinical
      surveillance identified 237 (60%) children in addition to laboratory
      surveillance. Ninety (24.3%) children were HIV co-infected; 113 (29.5%) had
      weight-for-age z-scores <- 3. Extra-pulmonary TB (EPTB) was diagnosed in 188
      (47.6%); 77 (19.5%) with disseminated TB. Favourable TB treatment outcomes were
      reported in 300/344 (87.2%) children with drug-susceptible and 50/51 (98.0%)
      children with drug-resistant TB. Older children (OR 1.7; 95% CI 1.0-2.8),
      children with EPTB (OR 2.3; 95% CI 1.5-3.6) and in-hospital deaths (OR 5.4; 95%
      CI 1.1-26.9) were more frequently detected by laboratory surveillance. TB/HIV co
      infected children were less likely to be identified through laboratory
      surveillance (OR 0.3; 95% CI 0.2-0.5). CONCLUSIONS: The burden and spectrum of
      childhood TB disease managed at referral hospital level in high burden settings
      is substantial. Hospital-based surveillance in addition to routine TB
      surveillance is essential to provide a complete picture of the burden, spectrum
      and impact of childhood TB in settings where hospitals are not TB reporting
      units.

PMID- 29566652
TI  - Yoga for posttraumatic stress disorder - a systematic review and meta-analysis.
AB  - BACKGROUND: Yoga is increasingly used as a therapeutic treatment and seems to
      improve psychiatric conditions such as anxiety disorders and depression. The aim
      of this systematic review was to assess the evidence of yoga for reducing
      symptoms of posttraumatic stress disorder (PTSD). METHODS: The Cochrane Library,
      Medline/PubMed, PsycINFO, Scopus, and IndMED were searched through July 2017 for
      randomized controlled trials (RCTs) assessing the effects of yoga on symptoms of
      PTSD. Mean differences (MD) and standardized mean differences (SMD) with 95%
      confidence intervals (CI) were computed. The quality of evidence and the strength
      of recommendation were graded according to the GRADE recommendations. RESULTS:
      Seven RCTs (N = 284) were included. Meta-analysis revealed low quality evidence
      for clinically relevant effects of yoga on PTSD symptoms compared to no treatment
      (SMD = - 1.10, 95% CI [- 1.72, - 0.47], p < .001, I2 = 72%; MD = - 13.11, 95% CI
      [- 17.95, - 8.27]); and very low evidence for comparable effects of yoga and
      attention control interventions (SMD = - 0.31, 95%CI = [- 0.84, 0.22], p = .25;
      I2 = 43%). Very low evidence was found for comparable retention of patients in
      the trial for yoga and no treatment (OR = 0.68, 95%CI [0.06, 7.72]) or attention
      control interventions (OR = 0.66, 95%CI [0.10, 4.46]). No serious adverse events
      were reported. LIMITATIONS: Few RCTs with only limited sample size were
      available. CONCLUSIONS: Only a weak recommendation for yoga as an adjunctive
      intervention for PTSD can be made. More high quality research is needed to
      confirm or disconfirm these findings.

PMID- 29566654
TI  - A quantitative analysis method for comitant exotropia using video-oculography
      with alternate cover.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of a
      quantitative analysis method for comitant exotropia using video-oculography (VOG)
      with alternate cover. METHODS: Thirty-four subjects with comitant exotropia were
      included. Two independent ophthalmologists measured the angle of ocular deviation
      using the alternate prism cover test (APCT). The video files and data of changes
      in ocular deviation during the alternate cover test were obtained using VOG. To
      verify the accuracy of VOG, the value obtained using VOG and the angle of a
      rotating model eye were compared, and a new linear equation was subsequently
      derived using these data. The calculated values obtained using VOG were compared
      with those obtained using the APCT. RESULTS: Rotation of the model eye and the
      values obtained using VOG demonstrated excellent positive correlation (R = 1.000;
      p < 0.001). A simple linear regression model was obtained: rotation of the model
      eye = 0.978 * value obtained using VOG for a model eye - 0.549. The 95% limit of
      agreement for inter-observer variability was +/-4.63 prism diopters (PD) for APCT
      and that for test-retest variability was +/-3.56 PD for the VOG test. The results
      of APCT and calculated VOG test demonstrated a strong positive correlation. Bland
      Altman plots revealed no overall tendency for the calculated values obtained from
      VOG to differ from those obtained using APCT. CONCLUSIONS: VOG with alternate
      cover is a non-invasive and accurate tool for quantitatively measuring and
      recording ocular deviation. In particular, it is independent of the proficiency
      of the examiner and, can therefore, be useful in the absence of skilled
      personnel. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03119311 , Date of
      registration: 04/17/2017, Date of enrolment of the first participant to the
      trial: 04/25/2017.

PMID- 29566653
TI  - Transcriptomic analysis reveals overdominance playing a critical role in nicotine
      heterosis in Nicotiana tabacum L.
AB  - BACKGROUND: As a unique biological phenomenon, heterosis has been concerned with
      the superior performance of the heterosis than either parents. Despite several F1
      hybrids, containing supernal nicotine content, had been discovered and applied to
      heterosis utilization in Nicotiana tabacum L., nevertheless, the potential
      molecular mechanism revealing nicotine heterosis has not been illustrated
      clearly. RESULT: Phenotypically, the F1 hybrids (Vall6 * Basma) show prominent
      heterosis in nicotine content by 3 years of field experiments. Transcriptome
      analysis revealed that genes participating in nicotine anabolism (ADC, PMT, MPO,
      QPT, AO, QS, QPT, A622, BBLs) and nicotine transport (JAT2, MATE1 and 2, NUP1 and
      2) showed an upregulated expression in the hybrid, a majority of which
      demonstrated an overdominant performance. RT-PCR confirmed that nicotine
      anabolism was induced in the hybrid. CONCLUSIONS: These findings strongly suggest
      that nicotine synthesis and transport efficiency improved in hybrid and
      overdominance at gene-expression level played a critical role in heterosis of
      nicotine metabolism.

PMID- 29566655
TI  - Maternal death and delays in accessing emergency obstetric care in Mozambique.
AB  - BACKGROUND: Despite declining trends maternal mortality remains an important
      public health issue in Mozambique. The delays to reach an appropriate health
      facility and receive care faced by woman with pregnancy related complications
      play an important role in the occurrence of these deaths. This study aims to
      examine the contribution of the delays in relation to the causes of maternal
      death in facilities in Mozambique. METHODS: Secondary analysis was performed on
      data from a national assessment on maternal and neonatal health that included in
      depth maternal death reviews, using patient files and facility records with the
      most comprehensive information available. Statistical models were used to assess
      the association between delay to reach the health facility that provides
      emergency obstetric care (delay type II) and delay in receiving appropriate care
      once reaching the health facility providing emergency obstetric care (delay type
      III) and the cause of maternal death within the health facility. RESULTS: Data
      were available for 712 of 2,198 maternal deaths. Delay type II was observed in
      40.4% of maternal deaths and delay type III in 14.2%.and 13.9% had both delays.
      Women who died of a direct obstetric complication were more likely to have
      experienced a delay type III than women who died due to indirect causes. Women
      who experienced delay type II were less likely to have also delay type III and
      vice versa. CONCLUSIONS: The delays in reaching and receiving appropriate
      facility-based care for women facing pregnancy related complications in
      Mozambique contribute significantly to maternal mortality. Securing referral
      linkages and health facility readiness for rapid and correct patient management
      are needed to reduce the impact of these delays within the health system.

PMID- 29566656
TI  - Efficacy and cost-effectiveness of a blended cognitive behavioral therapy for
      depression in Spanish primary health care: study protocol for a randomised non
      inferiority trial.
AB  - BACKGROUND: Data from primary health care in Spain show a high prevalence of the
      major depressive disorder. Blended treatment (combination of face-to-face and
      online components) seems to be a very promising tool for the optimization and
      dissemination of psychological treatments in a cost-effective form. Although
      there is growing data that confirm the advantages of blended therapies, few
      studies have analyzed their application in regular clinical practice. The
      objective of the present paper is to describe the protocol for a clinical study
      aimed at exploring the clinical and cost-effectiveness of a blended cognitive
      behavioral therapy (b-CBT) for depression, compared to treatment as usual (TAU)
      in a primary health care setting. METHODS: A two-arm randomised controlled non
      inferiority trial will be carried out, with repeated measures (baseline, 3
      months, 6 months, and 12 months) under two conditions: b-CBT and TAU. The b-CBT
      program will consist in three face-to-face sessions and eight online sessions.
      The TAU is defined as the routine care delivered by the general practitioner for
      the treatment of depression in primary care. The primary outcome is a symptomatic
      change of depressive symptoms on the patient-health questionnaire (PHQ-9). Other
      secondary outcomes will be considered (e.g., quality of life, treatment
      preference). All participants must be 18 years of age or older and meet the
      diagnostic criteria for major depressive disorder according to the Diagnostic and
      Statistical Manual of Mental disorders 4th edition. 156 participants will be
      recruited (78 per arm). DISCUSSION: It is expected that b-CBT is clinically non
      inferior when compared to TAU. This is the first study in Spain to use a b-CBT
      format in primary and specialized care, and this format could be an efficacious
      and cost-effective therapeutic strategy for the treatment of depression. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02361684. Registered on 8 January 2015.
      Currently recruiting participants.

PMID- 29566657
TI  - Germline breast cancer susceptibility gene mutations and breast cancer outcomes.
AB  - BACKGROUND: It is unclear whether germline breast cancer susceptibility gene
      mutations affect breast cancer related outcomes. We wanted to evaluate mutation
      patterns in 20 breast cancer susceptibility genes and correlate the mutations
      with clinical characteristics to determine the effects of these germline
      mutations on breast cancer prognosis. METHODS: The study cohort included 480
      ethnic Chinese individuals in Taiwan with at least one of the six clinical risk
      factors for hereditary breast cancer: family history of breast or ovarian cancer,
      young age of onset for breast cancer, bilateral breast cancer, triple negative
      breast cancer, both breast and ovarian cancer, and male breast cancer. PCR
      enriched amplicon-sequencing on a next generation sequencing platform was used to
      determine the germline DNA sequences of all exons and exon-flanking regions of
      the 20 genes. Protein-truncating variants were identified as pathogenic. RESULTS:
      We detected a 13.5% carrier rate of pathogenic germline mutations, with BRCA2
      being the most prevalent and the non-BRCA genes accounting for 38.5% of the
      mutation carriers. BRCA mutation carriers were more likely to be diagnosed of
      breast cancer with lymph node involvement (66.7% vs 42.6%; P = 0.011), and had
      significantly worse breast cancer specific outcomes. The 5-year disease-free
      survival was 73.3% for BRCA mutation carriers and 91.1% for non-carriers (hazard
      ratio for recurrence or death 2.42, 95% CI 1.29-4.53; P = 0.013). After adjusting
      for clinical prognostic factors, BRCA mutation remained an independent poor
      prognostic factor for cancer recurrence or death (adjusted hazard ratio 3.04, 95%
      CI 1.40-6.58; P = 0.005). Non-BRCA gene mutation carriers did not exhibit any
      significant difference in cancer characteristics or outcomes compared to those
      without detected mutations. Among the risk factors for hereditary breast cancer,
      the odds of detecting a germline mutation increased significantly with having
      bilateral breast cancer (adjusted odds ratio 3.27, 95% CI 1.64-6.51; P = 0.0008)
      or having more than one risk factor (odds ratio 2.07, 95% CI 1.22-3.51; P =
      0.007). CONCLUSIONS: Without prior knowledge of the mutation status, BRCA
      mutation carriers had more advanced breast cancer on initial diagnosis and worse
      cancer-related outcomes. Optimal approach to breast cancer treatment for BRCA
      mutation carriers warrants further investigation.

PMID- 29566658
TI  - Punch biopsies shorten time to clearance of high-risk human papillomavirus
      infections of the uterine cervix.
AB  - BACKGROUND: The primary objective was to determine human papilloma virus (HPV)
      clearance rate after cervical biopsy among women with persistent high-risk HPV
      infection compared with spontaneous HPV clearance rate in the absence of biopsy.
      METHODS: We collected data from a dedicated screening program of women aged 30-70
      years old. Inclusion criteria for the baseline non-interventional cohort were a
      positive HPV test (hybrid capture 2, HC2) and normal cytology. In the baseline
      cohort women were followed with approximately yearly HPV-tests and cytology until
      HPV regressed (one negative HPV test) or interventions in the form of diagnostic
      biopsies or therapy. Women who had a diagnostic biopsy were included in the
      biopsy cohort and followed until HPV regression or therapy. Observed HPV
      regression rates and time to HPV regression were compared between baseline and
      biopsy cohorts. For the comparison, we used Fisher's exact test for the HPV
      regression rates and interval-censored, accelerated failure time model for time
      to HPV regression. RESULTS: Among the 1079 women included in the baseline cohort,
      499 (46.3%) had HPV clearance and 475 were referred for colposcopy with biopsy.
      The biopsy cohort comprised all women who were not treated and had at least one
      HC2 test after biopsy (201/475; 42.3%). Of those, 138 (68.7%) experienced HPV
      regression. In the biopsy cohort, time to clearance of HPV infection was
      approximately halved (0.46, 95% CI 0.38-0.56) compared with the baseline cohort.
      This result was robust in a wide range of sensitivity analyses. CONCLUSIONS: A
      higher proportion of women cleared their HPV infection, and time to HPV clearance
      was shorter in the biopsy cohort than in the baseline cohort. It is reassuring
      for clinicians to know that conservative management of patients with HPV
      persistency is successful when colposcopy with biopsies excludes high-grade
      disease.

PMID- 29566659
TI  - Accelerating newborn survival in Ghana through a low-dose, high-frequency health
      worker training approach: a cluster randomized trial.
AB  - BACKGROUND: Newborn deaths comprise nearly half of under-5 deaths in Ghana,
      despite the fact that skilled birth attendants (SBAs) are present at 68% of
      births, which implies that evidence-based care during labor, birth and the
      immediate postnatal period may be deficient. We assessed the effect of a low
      dose, high-frequency (LDHF) training approach on long-term evidence-based skill
      retention among SBAs and impact on adverse birth outcomes. METHODS: From 2014 to
      2017, we conducted a cluster-randomized trial in 40 hospitals in Ghana. Eligible
      hospitals were stratified by region and randomly assigned to one of four
      implementation waves. We assessed the relative risks (RRs) of institutional
      intrapartum stillbirths and 24-h newborn mortality in months 1-6 and 7-12 of
      implementation as compared to the historical control period, and in post
      intervention facilities compared to pre-intervention facilities during the same
      period. All SBAs providing labor and delivery care were invited to enroll; their
      knowledge and skills were assessed pre- and post-training, and 1 year later.
      RESULTS: Adjusting for region and health facility type, the RR of 24-h newborn
      mortality in the 40 enrolled hospitals was 0.41 (95% CI 0.32-0.51; p < 0.001) in
      months 1-6 and 0.30 (95% CI 0.21-0.43; p < 0.001) in months 7-12 compared to
      baseline. The adjusted RR of intrapartum stillbirth was 0.64 (95% CI 0.53-0.77; p
      < 0.001) in months 1-6 and 0.48 (95% CI 0.36-0.63; p < 0.001) in months 7-12
      compared to baseline. Four hundred three SBAs consented and enrolled. After 1
      year, 200 SBAs assessed had 28% (95% CI 25-32; p < 0.001) and 31% (95% CI 27-36;
      p < 0.001) higher scores than baseline on low-dose 1 and 2 content skills,
      respectively. CONCLUSIONS: This training approach results in a sustained decrease
      in facility-based newborn mortality and intrapartum stillbirths, and retained
      knowledge and skills among SBAs after a year. We recommend use of this approach
      for future maternal and newborn health in-service training and programs. TRIAL
      REGISTRATION: Retrospectively registered on 25 September 2017 at Clinical Trials,
      identifier NCT03290924 .

PMID- 29566660
TI  - Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant
      Mycobacterium tuberculosis in Kyrgyz Republic.
AB  - BACKGROUND: The aim of this study was to identify mutations of rpoB, katG, inhA
      and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin
      (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from
      the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium
      tuberculosis susceptibility to RIF and INH using culture method of absolute
      concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB,
      Moscow, Russian Federation). RESULTS: For RIF-resistance, TB-BIOCHIP's
      sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and
      90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP
      showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533
      (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 >
      Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG
      gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315->Thr (88.6%) was the most
      prevalent mutation leading to resistance to INH. CONCLUSIONS: In Kyrgyz Republic,
      the most prevalent mutation in RIF-resistant strains was Ser531 -> Leu in rpoB
      gene, as opposed to Ser315 -> Thr in katG gene in INH-resistant Mycobacterium
      tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium
      tuberculosis were strains with combined mutations Ser531 -> Leu in rpoB gene and
      Ser315 -> Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the
      advantage of obtaining results in only two days.

PMID- 29566661
TI  - Blocking hexose entry into glycolysis activates alternative metabolic conversion
      of these sugars and upregulates pentose metabolism in Aspergillus nidulans.
AB  - BACKGROUND: Plant biomass is the most abundant carbon source for many fungal
      species. In the biobased industry fungi, are used to produce lignocellulolytic
      enzymes to degrade agricultural waste biomass. Here we evaluated if it would be
      possible to create an Aspergillus nidulans strain that releases, but does not
      metabolize hexoses from plant biomass. For this purpose, metabolic mutants were
      generated that were impaired in glycolysis, by using hexokinase (hxkA) and
      glucokinase (glkA) negative strains. To prevent repression of enzyme production
      due to the hexose accumulation, strains were generated that combined these
      mutations with a deletion in creA, the repressor involved in regulating
      preferential use of different carbon catabolic pathways. RESULTS: Phenotypic
      analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran.
      However, hexoses did not accumulate during growth of the mutants on wheat bran,
      suggesting that glucose metabolism is re-routed towards alternative carbon
      catabolic pathways. The creADelta4 mutation in combination with preventing
      initial phosphorylation in glycolysis resulted in better growth than the
      hxkA/glkA mutant and an increased expression of pentose catabolic and pentose
      phosphate pathway genes. This indicates that the reduced ability to use hexoses
      as carbon sources created a shift towards the pentose fraction of wheat bran as a
      major carbon source to support growth. CONCLUSION: Blocking the direct entry of
      hexoses to glycolysis activates alternative metabolic conversion of these sugars
      in A. nidulans during growth on plant biomass, but also upregulates conversion of
      other sugars, such as pentoses.

PMID- 29566662
TI  - Age greater than 60 years portends a worse prognosis in patients with papillary
      thyroid cancer: should there be three age categories for staging?
AB  - BACKGROUND: Age is an important prognostic factor in papillary thyroid cancer
      (PTC), with better survival observed in patients < 45 years of age, regardless of
      stage. Although the impact of increasing age on PTC-related survival is well
      known, previous studies have focused on survival relative to age 45 years only.
      As the number of patients entering their 7th decade of life increases, PTC
      related survival in this demographic becomes increasingly important. Survival in
      patients >= 60 years specifically compared to other groups has not previously
      been examined. We sought to determine whether age >= 60 years is an adverse
      prognostic factor for disease-specific survival and recurrence in patients with
      PTC. METHODS: The California Cancer Registry database was linked to inpatient and
      ambulatory patient records from the Office of Statewide Health Planning and
      Development for the years 2000-2011. This linked database was queried for
      patients diagnosed with papillary thyroid cancer and treated with surgery. We
      then identified prognostic factors related to both 5-year and 10-year disease
      specific survival and disease-free survival in patients <= 45, 45-59, and >= 60
      years. Multivariable Cox proportional hazard models were created to test the
      effect of age >= 60 on disease-specific and disease-free survival, controlling
      for clinical, treatment, and demographic factors. RESULTS: The final cohort
      included 15,675 patients. Of the group, 46.3% were between 18 and 44 years of
      age, 33.6% were 45-59 years, and 20.1% were >= 60. Univariate analysis showed
      that compared to other groups, patients >= 60 were more likely to be male (p <
      0.001), present with tumors > 5 cm (p < 0.001), more likely to have metastatic
      disease (p < 0.001), less likely to receive radioactive iodine (p < 0.001), and
      more likely to receive external beam radiation therapy (p < 0.001). In
      multivariable Cox proportional hazards models for 5 and 10-year disease-free
      survival, age >= 60 was associated with higher risk of disease at 5 and 10-years
      (HR 2.3 and 1.9 respectively, p < 0.001). Similar results were observed for 5 and
      10-year disease-specific survival (HR 38.0 and 30.0 respectively, p < 0.001)
      after controlling for gender, race, co-morbidity, stage, surgical procedure,
      radioactive iodine, insurance, and hospital volume. CONCLUSIONS: Patients >= 60
      years of age have worse DSS and DFS after a diagnosis of PTC, across all stages
      of disease. Given that patients over the age of 45 years have progressively worse
      survival as they age, these data support having three age groups, 18-44 years of
      age, 45-59 years, and >= 60 as an independent predictor of survival and
      recurrence to current staging guidelines.

PMID- 29566663
TI  - Unconditional and conditional QTL analyses of seed fatty acid composition in
      Brassica napus L.
AB  - BACKGROUND: The fatty acid composition of B. napus' seeds determines the oil's
      nutritional and industrial values, and affects seed germination. Many studies
      have reported correlations among C16:0, C18:0, C18:1, C18:2 and C18:3 based on
      phenotypic data; however, the genetic basis of the fatty acid composition in B.
      napus is still not well understood. RESULTS: In this study, unconditional and
      conditional quantitative trail locus (QTL) mapping analyses were conducted using
      a recombinant inbred line in six environments. In total, 21 consensus QTLs each
      for C16:0, C18:0 and C18:2, 16 for C18:1 and 22 for C18:3 were detected by
      unconditional mapping. The QTLs with overlapping confidence intervals were
      integrated into 71 pleiotropically unique QTLs by meta-analysis. Two major QTLs,
      uuqA5-6 and uuqA5-7, simultaneously affected the fatty acids, except C18:0, in
      most of environments, with the homologous genes fatty acid desaturase 2 (FAD2)
      and glycerol-3-phosphate sn-2-acyltransferase 5 (GPAT5) occurring in the
      confidence interval of uuqA5-6, while phosphatidic acid phosphohydrolase 1 (PAH1)
      was assigned to uuqA5-7. Moreover, 49, 30, 48, 60 and 45 consensus QTLs were
      detected for C16:0, C18:0, C18:1, C18:2 and C18:3, respectively, by the
      conditional mapping analysis. In total, 128 unique QTLs were subsequently
      integrated from the 232 conditional consensus QTLs. A comparative analysis
      revealed that 63 unique QTLs could be identified by both mapping methodologies,
      and 65 additional unique QTLs were only identified in conditional mapping.
      CONCLUSIONS: Thus, conditional QTL mapping for fatty acids may uncover numerous
      additional QTLs that were inhibited by the effects of other traits. These
      findings provide useful information for better understanding the genetic
      relationships among fatty acids at the QTL level.

PMID- 29566664
TI  - Rival seminal fluid induces enhanced sperm motility in a polyandrous ant.
AB  - BACKGROUND: Promiscuous mating and sperm competition often induce arms races
      between the sexes with detrimental outcomes for females. However, ants with
      multiply-inseminated queens have only a single time-window for sperm competition
      and queens are predicted to gain control over the outcome of sperm storage
      quickly. The seminal fluid of Acromyrmex leaf-cutting ants reduces the viability
      of rival sperm, but how confrontations between unrelated ejaculates affect sperm
      storage remains unknown. RESULTS: We investigated the effects of ejaculate
      admixture on sperm motility in A. echinatior and found that the proportion of
      motile spermatozoa, sperm swimming speed, and linearity of sperm movement
      increased when rival ejaculates were mixed in vitro. Major effects induced by the
      seminal fluid of rival males were of similar magnitude to those generated by
      queen reproductive tract secretions, whereas own seminal fluid induced lower
      sperm activation levels. CONCLUSIONS: Our results suggest that ant sperm respond
      via a self-non-self recognition mechanism to similar or shared molecules
      expressed in the reproductive secretions of both sexes. Lower sperm motility in
      the presence of own seminal fluid indicates that enhanced motility is costly and
      may trade-off with sperm viability during sperm storage, consistent with studies
      in vertebrates. Our results imply that ant spermatozoa have evolved to adjust
      their energetic expenditure during insemination depending on the perceived level
      of sperm competition.

PMID- 29566665
TI  - Development of a measurement approach to assess time children participate in
      organized sport, active travel, outdoor active play, and curriculum-based
      physical activity.
AB  - BACKGROUND: Children participate in four main types of physical activity:
      organized sport, active travel, outdoor active play, and curriculum-based
      physical activity. The objective of this study was to develop a valid approach
      that can be used to concurrently measure time spent in each of these types of
      physical activity. METHODS: Two samples (sample 1: n = 50; sample 2: n = 83) of
      children aged 10-13 wore an accelerometer and a GPS watch continuously over 7
      days. They also completed a log where they recorded the start and end times of
      organized sport sessions. Sample 1 also completed an outdoor time log where they
      recorded the times they went outdoors and a description of the outdoor activity.
      Sample 2 also completed a curriculum log where they recorded times they
      participated in physical activity (e.g., physical education) during class time.
      RESULTS: We describe the development of a measurement approach that can be used
      to concurrently assess the time children spend participating in specific types of
      physical activity. The approach uses a combination of data from accelerometers,
      GPS, and activity logs and relies on merging and then processing these data using
      several manual (e.g., data checks and cleaning) and automated (e.g., algorithms)
      procedures. In the new measurement approach time spent in organized sport is
      estimated using the activity log. Time spent in active travel is estimated using
      an existing algorithm that uses GPS data. Time spent in outdoor active play is
      estimated using an algorithm (with a sensitivity and specificity of 85%) that was
      developed using data collected in sample 1 and which uses all of the data
      sources. Time spent in curriculum-based physical activity is estimated using an
      algorithm (with a sensitivity of 78% and specificity of 92%) that was developed
      using data collected in sample 2 and which uses accelerometer data collected
      during class time. There was evidence of excellent intra- and inter-rater
      reliability of the estimates for all of these types of physical activity when the
      manual steps were duplicated. CONCLUSIONS: This novel measurement approach can be
      used to estimate the time that children participate in different types of
      physical activity.

PMID- 29566666
TI  - Assessing linkage to and retention in care among HIV patients in Uganda and
      identifying opportunities for health systems strengthening: a descriptive study.
AB  - BACKGROUND: While antiretroviral therapy (ART) availability for HIV patients has
      increased dramatically in Uganda, patient linkage to and retention in care
      remains a challenge. We assessed patterns of engagement in care in 20 Ugandan
      health facilities with low retention based on national reporting. METHODS: We
      assessed patient linkage to care (defined as registering for pre-ART or ART care
      at the facility within 1 month of HIV diagnosis) and 6-month retention in care
      (having a visit 3-6 months after ART initiation) and associations with patient
      /facility-level factors using multivariate logistic regression. RESULTS: Among
      928 newly HIV-diagnosed patients, only 53.0% linked to care within 1 month. Of
      these, 83.7% linked within 1 week. Among 678 newly initiated ART patients, 14.5%
      never returned for a follow-up visit at the facility. Retention was 71.7%
      according to our primary definition but much lower if stricter definitions were
      used. Most patients were already falling behind appointment schedules at their
      first ART follow-up (median: 28 days post-initiation vs. recommended 14 days).
      27.3% of newly-initiated patients had follow-up appointments scheduled 45+ days
      apart rather than monthly per national guidelines. Linkage and retention were not
      strongly correlated with each other within facilities (rs = 0.06; p = 0.82).
      Females, adolescents, and patients in rural settings tended to have lower linkage
      and retention in multivariable-adjusted models. CONCLUSIONS: Linkage support may
      be most critical immediately after testing positive, as patients are less likely
      to link over time. More information is needed on reasons for appointment
      schedules by clinicians and implications on retention. TRIAL REGISTRATION: This
      study was registered in the Pan African Clinical Trial Registry database
      (#PACTR201611001756166).

PMID- 29566667
TI  - Work-related adverse events leaving their mark: a cross-sectional study among
      Dutch gynecologists.
AB  - BACKGROUND: Health care professionals who are frequently coping with traumatic
      events have an increased risk of developing a posttraumatic stress disorder.
      Research among physicians is scarce, and obstetrician-gynecologists may have a
      higher risk. Work-related traumatic events and posttraumatic stress disorder
      among obstetricians-gynecologists and the (desired) type of support were studied.
      METHODS: A questionnaire was emailed to all members of the Dutch Society of
      Obstetrics and Gynaecology, which included residents, attending, retired and non
      practicing obstetricians-gynecologists. The questionnaire included questions
      about personal experiences and opinions concerning support after work-related
      events, and a validated questionnaire for posttraumatic stress disorder. RESULTS:
      The response rate was 42.8% with 683 questionnaires eligible for analysis. 12.6%
      of the respondents have experienced a work-related traumatic event, of which
      11.8% met the criteria for current posttraumatic stress disorder. This revealed
      an estimated prevalence of 1.5% obstetricians-gynecologists with current
      posttraumatic stress disorder. 12% reported to have a support protocol or
      strategy in their hospital after adverse events. The most common strategies to
      cope with emotional events were: to seek support from colleagues, to seek support
      from family or friends, to discuss the case in a complication meeting or audit
      and to find distraction. 82% would prefer peer-support with direct colleagues
      after an adverse event. CONCLUSIONS: This survey implies that work-related events
      can be traumatic and subsequently can lead to posttraumatic stress disorder.
      There is a high prevalence rate of current posttraumatic stress disorder among
      obstetricians-gynecologists. Often there is no standardized support after adverse
      events. Most obstetrician-gynecologists prefer peer-support with direct
      colleagues after an adverse event. More awareness must be created during medical
      training and organized support must be implemented.

PMID- 29566668
TI  - Oral medicine acceptance in infants and toddlers: measurement properties of the
      caregiver-administered Children's acceptance tool (CareCAT).
AB  - BACKGROUND: Developing age-appropriate medications remains a challenge in
      particular for the population of infants and toddlers, as they are not able to
      reliably self-report if they would accept and consequently take an oral medicine.
      Therefore, it is common to use caregivers as proxies when assessing medicine
      acceptance. The outcome measures used in this research field differ and most
      importantly lack validation, implying a persisting gap in knowledge and
      controversy in the field. The newly developed Caregiver-administered Children's
      Acceptance Tool (CareCAT) is based on a 5-point nominal scale, with descriptors
      of medication acceptance behavior. This cross-sectional study assessed the
      measurement properties of the tool with regards to the user's understanding and
      its intra- and inter-rater reliability. METHODS: Participating caregivers were
      enrolled at a primary healthcare facility where their children (median age 6
      months) had been prescribed oral antibiotics. Caregivers, trained observers and
      the tool developer observed and scored on the CareCAT tool what behavior children
      exhibited when receiving the medicine (n = 104). The video-records of this
      process served as replicate observations (n = 69). After using the tool
      caregivers were asked to explain their observations and the tool descriptors in
      their own words. The tool's reliability was assessed by percentage agreement and
      Cohen's unweighted kappa coefficients of agreement for nominal scales. RESULTS:
      The study found that caregivers using CareCAT had a satisfactory understanding of
      the tool's descriptors. Using its dichotomized scores the tool reliably was
      strong for acceptance behavior (agreement inter-rater 84-88%, kappa 0.66-0.76;
      intra-rater 87-89%, kappa 0.68-0.72) and completeness of medicine ingestion
      (agreement inter-rater 82-86%, kappa 0.59-0.67; intra-rater 85-93%, kappa 0.50
      0.70). CONCLUSIONS: The CareCAT is a low-cost, easy-to-use and reliable
      instrument, which is relevant to assess acceptance behavior and completeness of
      medicine ingestion, both of which are of significant importance for developing
      age-appropriate medications in infants and toddlers.

PMID- 29566669
TI  - RNA sequencing of early round goby embryos reveals that maternal experiences can
      shape the maternal RNA contribution in a wild vertebrate.
AB  - BACKGROUND: It has been proposed that non-genetic inheritance could promote
      species fitness. Non-genetic inheritance could allow offspring to benefit from
      the experience of their parents, and could advocate pre-adaptation to prevailing
      and potentially selective conditions. Indeed, adaptive parental effects have been
      modeled and observed, but the molecular mechanisms behind them are far from
      understood. RESULTS: In the present study, we investigated whether maternal RNA
      can carry information about environmental conditions experienced by the mother in
      a wild vertebrate. Maternal RNA directs the development of the early embryo in
      many non-mammalian vertebrates and invertebrates. However, it is not known
      whether vertebrate maternal RNA integrates information about the parental
      environment. We sequenced the maternal RNA contribution from a model that we
      expected to rely on parental effects: the invasive benthic fish species Neogobius
      melanostomus (Round Goby). We found that maternal RNA expression levels
      correlated with the water temperature experienced by the mother before
      oviposition, and identified temperature-responsive gene groups such as core
      nucleosome components or the microtubule cytoskeleton. CONCLUSIONS: Our findings
      suggest that the maternal RNA contribution may incorporate environmental
      information. Maternal RNA should therefore be considered a potentially relevant
      pathway for non-genetic inheritance. Also, the ability of a species to integrate
      environmental information in the maternal RNA contribution could potentially
      contribute to species fitness and may also play a role in extraordinary adaptive
      success stories of invasive species such as the round goby.

PMID- 29566670
TI  - The DNA methylation profile of liver tumors in C3H mice and identification of
      differentially methylated regions involved in the regulation of tumorigenic
      genes.
AB  - BACKGROUND: C3H mice have been frequently used in cancer studies as animal models
      of spontaneous liver tumors and chemically induced hepatocellular carcinoma
      (HCC). Epigenetic modifications, including DNA methylation, are among pivotal
      control mechanisms of gene expression leading to carcinogenesis. Although
      information on somatic mutations in liver tumors of C3H mice is available,
      epigenetic aspects are yet to be clarified. METHODS: We performed next generation
      sequencing-based analysis of DNA methylation and microarray analysis of gene
      expression to explore genes regulated by DNA methylation in spontaneous liver
      tumors of C3H mice. Overlaying these data, we selected cancer-related genes whose
      expressions are inversely correlated with DNA methylation levels in the
      associated differentially methylated regions (DMRs) located around transcription
      start sites (TSSs) (promoter DMRs). We further assessed mutuality of the selected
      genes for expression and DNA methylation in human HCC using the Cancer Genome
      Atlas (TCGA) database. RESULTS: We obtained data on genome-wide DNA methylation
      profiles in the normal and tumor livers of C3H mice. We identified promoter DMRs
      of genes which are reported to be related to cancer and whose expressions are
      inversely correlated with the DNA methylation, including Mst1r, Slpi and Extl1.
      The association between DNA methylation and gene expression was confirmed using a
      DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) in Hepa1c1c7 cells
      and Hepa1-6 cells. Overexpression of Mst1r in Hepa1c1c7 cells illuminated a novel
      downstream pathway via IL-33 upregulation. Database search indicated that gene
      expressions of Mst1r and Slpi are upregulated and the TSS upstream regions are
      hypomethylated also in human HCC. These results suggest that DMRs, including
      those of Mst1r and Slpi, are involved in liver tumorigenesis in C3H mice, and
      also possibly in human HCC. CONCLUSIONS: Our study clarified genome wide DNA
      methylation landscape of C3H mice. The data provide useful information for
      further epigenetic studies of mice models of HCC. The present study particularly
      proposed novel DNA methylation-regulated pathways for Mst1r and Slpi, which may
      be applied not only to mouse HCC but also to human HCC.

PMID- 29566671
TI  - Completing sparse and disconnected protein-protein network by deep learning.
AB  - BACKGROUND: Protein-protein interaction (PPI) prediction remains a central task
      in systems biology to achieve a better and holistic understanding of cellular and
      intracellular processes. Recently, an increasing number of computational methods
      have shifted from pair-wise prediction to network level prediction. Many of the
      existing network level methods predict PPIs under the assumption that the
      training network should be connected. However, this assumption greatly affects
      the prediction power and limits the application area because the current golden
      standard PPI networks are usually very sparse and disconnected. Therefore, how to
      effectively predict PPIs based on a training network that is sparse and
      disconnected remains a challenge. RESULTS: In this work, we developed a novel PPI
      prediction method based on deep learning neural network and regularized Laplacian
      kernel. We use a neural network with an autoencoder-like architecture to
      implicitly simulate the evolutionary processes of a PPI network. Neurons of the
      output layer correspond to proteins and are labeled with values (1 for
      interaction and 0 for otherwise) from the adjacency matrix of a sparse
      disconnected training PPI network. Unlike autoencoder, neurons at the input layer
      are given all zero input, reflecting an assumption of no a priori knowledge about
      PPIs, and hidden layers of smaller sizes mimic ancient interactome at different
      times during evolution. After the training step, an evolved PPI network whose
      rows are outputs of the neural network can be obtained. We then predict PPIs by
      applying the regularized Laplacian kernel to the transition matrix that is built
      upon the evolved PPI network. The results from cross-validation experiments show
      that the PPI prediction accuracies for yeast data and human data measured as AUC
      are increased by up to 8.4 and 14.9% respectively, as compared to the baseline.
      Moreover, the evolved PPI network can also help us leverage complementary
      information from the disconnected training network and multiple heterogeneous
      data sources. Tested by the yeast data with six heterogeneous feature kernels,
      the results show our method can further improve the prediction performance by up
      to 2%, which is very close to an upper bound that is obtained by an Approximate
      Bayesian Computation based sampling method. CONCLUSIONS: The proposed evolution
      deep neural network, coupled with regularized Laplacian kernel, is an effective
      tool in completing sparse and disconnected PPI networks and in facilitating
      integration of heterogeneous data sources.

PMID- 29566672
TI  - Characteristics of exercise capacity in female systemic lupus erythematosus
      associated pulmonary arterial hypertension patients.
AB  - BACKGROUND: To study the oxygen uptake efficiency and determine usefulness of
      submaximal parameters of oxygen uptake in systemic lupus erythematosus associated
      pulmonary arterial hypertension (SLE PAH) on performing a cardiopulmonary
      exercise test (CPET). METHODS: CPET was performed in 21 SLE PAH patients, equal
      number of idiopathic pulmonary arterial hypertension (IPAH) patients and
      controls. Peak VO2, anaerobic threshold (AT), oxygen uptake efficiency slope
      (OUES) and oxygen uptake efficiency plateau (OUEP) and other CPET parameters were
      examined. All subjects had pulmonary function test (PFT) at rest, which included
      FEV1, FVC, FEV1/FVC, DLCO measurements. Right heart catheterization (RHC) was
      also done in SLE PAH and IPAH patients. CPET parameters were compared with RHC
      parameters to determine potential correlations. RESULTS: Peak VO2, PETCO2 and
      peak O2 pulse were lower in SLE PAH than IPAH and controls with OUE being lower
      during all stages of exercise in SLE PAH. DLCO and FVC values were significantly
      lower in SLE PAH (p < 0.05). Peak O2 pulse and VO2@AT in SLE PAH and IPAH was low
      (p < 0.05) and significant difference between SLE PAH and IPAH was seen (p <
      0.05). PVR correlated with the lowest VE/VCO2, O2 pulse, peak PETCO2 and OUE in
      SLE PAH patients (all p < 0.05). CONCLUSIONS: SLE PAH patients have
      cardiopulmonary exercise limitation with reduced oxygen uptake efficiency. VO2@
      at AT, peak O2 pulse and O2 pulse at AT were significantly reduced (p < 0.05).
      Key CPET parameters correlated with elevated pulmonary vascular resistance (PVR).
      Submaximal parameters of oxygen uptake are equally useful in SLE PAH.

PMID- 29566673
TI  - Implementation of grip strength measurement in medicine for older people wards as
      part of routine admission assessment: identifying facilitators and barriers using
      a theory-led intervention.
AB  - BACKGROUND: Low grip strength in older inpatients is associated with poor
      healthcare outcomes including longer length of stay and mortality. Measuring grip
      strength is simple and inexpensive. However, it is not routinely used in clinical
      practice. We aimed to evaluate the implementation of grip strength measurement
      into routine clinical practice. METHODS: This implementation study was a mixed
      methods study based in five acute medical wards for older people in one UK
      hospital. Intervention design and implementation evaluation were based on
      Normalization Process Theory (NPT). A training program was developed and
      delivered to enable staff to measure grip strength and use a care plan for
      patients with low grip strength. Routine implementation and monitoring was
      assessed using the "implementation outcome variables" proposed by WHO: adoption,
      coverage, acceptability, fidelity, and costs analysis. Enablers and barriers of
      implementation were identified. RESULTS: One hundred fifty-five nursing staff
      were trained, 63% in just 3 weeks. Adoption and monthly coverage of grip strength
      measurement varied between 25 and 80% patients across wards. 81% of female
      patients and 75% of male patients assessed had low grip strength (< 27 kg for men
      and < 16 kg for women). Staff and patients found grip measurement easy, cheap and
      potentially beneficial in identifying high-risk patients. The total cost of
      implementation across five wards over 12 months was less than L2302. Using NPT,
      interviews identified enablers and barriers. Enablers included: highly motivated
      ward champions, managerial support, engagement strategies, shared commitment, and
      integration into staff and ward daily routines. Barriers included lack of
      managerial and staff support, and high turnover of staff, managers and champions.
      CONCLUSIONS: Training a large number of nurses to routinely implement grip
      strength measurement of older patients was feasible, acceptable and inexpensive.
      Champions' motivation, managerial support, and shared staff commitment were
      important for the uptake and normalisation of grip strength measurement. A high
      percentage of older patients were identified to be at risk of poor healthcare
      outcomes and would benefit from nutritional and exercise interventions. Measuring
      grip strength in these patients could provide an opportunity to identify those
      with normal grip strength for fast tracking through admission to discharge
      thereby reducing length of stay. TRIAL REGISTRATION: Clinicaltrials.gov
      NCTO2447445 . Registered May 18, 2015.

PMID- 29566674
TI  - A genome-wide association study identifies candidate loci associated to
      syringomyelia secondary to Chiari-like malformation in Cavalier King Charles
      Spaniels.
AB  - BACKGROUND: Syringomyelia (SM) is a common condition affecting brachycephalic toy
      breed dogs and is characterized by the development of fluid-filled cavities
      within the spinal cord. It is often concurrent with a complex developmental
      malformation of the skull and craniocervical vertebrae called Chiari-like
      malformation (CM) characterized by a conformational change and overcrowding of
      the brain and cervical spinal cord particularly at the craniocervical junction.
      CM and SM have a polygenic mode of inheritance with variable penetrance. RESULTS:
      We identified six cranial T1-weighted sagittal MRI measurements that were
      associated to maximum transverse diameter of the syrinx cavity. Increased syrinx
      transverse diameter has been correlated previously with increased likelihood of
      behavioral signs of pain. We next conducted a whole genome association study of
      these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32
      with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be
      significantly associated to two traits associated with a reduced volume and
      altered orientation of the caudal cranial fossa. Their reconstructed haplotypes
      defined two associated regions that harbor only two genes: PCDH17 on CFA22 and
      ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically
      in the brain and spinal cord. ZWINT plays a role in chromosome segregation and
      its expression is increased with the onset of neuropathic pain. Targeted genomic
      sequencing of these regions identified respectively 37 and 339 SNPs with
      significantly associated P values. Genotyping of tagSNPs selected from these 2
      candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM
      affected) identified 2 SNPs on CFA22 that were significantly associated to SM
      strengthening the candidacy of this locus in SM development. CONCLUSIONS: We
      identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and
      ZWINT, significantly associated to two traits associated with syrinx transverse
      diameter. The locus on CFA22 was significantly associated to SM secondary to CM
      in the CKCS dog breed strengthening its candidacy for this disease. This study
      will provide an entry point for identification of the genetic factors
      predisposing to this condition and its underlying pathogenic mechanisms.

PMID- 29566675
TI  - Development of the great recess framework - observational tool to measure
      contextual and behavioral components of elementary school recess.
AB  - BACKGROUND: Physical activity (PA) remains the primary behavioral outcome
      associated with school recess, while many other potentially relevant indicators
      of recess remain unexamined. Few studies have assessed observations of
      teacher/student interactions, peer conflict, social interactions, or safety
      within the recess environment. Furthermore, a psychometrically-sound instrument
      does not exist to examine safety, resources, student engagement, adult
      engagement, pro-social/anti-social behavior, and student empowerment on the
      playground. The purpose of the current study was to develop a valid, and
      reliable, assessment tool intended for use in measurement of the contextual
      factors associated with recess. METHODS: An iterative and multi-step process was
      used to develop a tool that measures safety and structure, adult engagement and
      supervision, student behaviors, and transitions at recess. Exploratory structural
      equation modeling (Mplus v. 7.4) was used to examine the underlying measurement
      model with observational data of the recess environment collected at 649 school
      based recess periods that spanned across 22 urban/metropolitan areas in the USA.
      Data were also collected by two researchers at 162 recess sessions across 9
      schools to examine reliability. RESULTS: A 17-item observation instrument, the
      Great Recess Framework - Observational Tool (GRF-OT), was created. Findings of
      exploratory structural equation modeling (ESEM) analyses supported factorial
      validity for a 4-factor solution and linear regressions established convergent
      validity where 'structure and safety', 'adult engagement and supervision', and
      'student behaviors' were all significantly related to observed activity levels.
      Each sub-scale of the GRF-OT showed adequate levels of inter-rater reliability
      and test-retest reliability analysis indicated a higher level of stability for
      the GRF-OT when using a three-day average across two time points as compared to a
      two-day average. CONCLUSIONS: Initial evidence for a valid, and reliable,
      assessment tool to observationally measure the recess environment with a specific
      focus on safety, resources, student engagement, adult engagement, pro-social/anti
      social behavior, and student empowerment was established in this study. Use of
      the GRF-OT can inspire evaluation, and subsequent intervention, to strategically
      create consistent, appropriate, and engaging school recess that impact children's
      physical, cognitive, social and emotional development.

PMID- 29566676
TI  - Correction to: HbA1c versus oral glucose tolerance test as a method to diagnose
      diabetes mellitus in vascular surgery patients.
AB  - The authors found errors in Table 1 after publication of the original article
      [1].The correct values for medical history of coronary artery disease (CAD) at
      baseline are 110 (40%) of all patients, 54 (35.5%) of patients categorized as
      having normoglycaemia, 42 (46.7%) of patients categorized as having intermediate
      hyperglycaemia, and 14 (42.4%) of patients categorized as having DM.All presented
      numbers and calculations in Table 1 are checked. No other errors were found. The
      presented errors did not affect results, scientific content or conclusions.The
      corrected Table 1 is presented in this erratum.The authors apologize for having
      presented this error in the original article.

PMID- 29566678
TI  - Impact of a 15-month multi-channel continuous distribution pilot on ITN ownership
      and access in Eastern Region, Ghana.
AB  - BACKGROUND: Insecticide-treated nets are a key intervention for malaria
      prevention. While mass distribution can rapidly scale up ITN coverage, multiple
      channels may be needed to sustain high levels of ITN access and ownership. In
      Ghana's Eastern Region, a continuous ITN distribution pilot, started in October
      2012, 18-24 months after a mass campaign. The pilot distributed ITNs through
      antenatal care services (ANC), child welfare clinic services (CWC) through the
      Expanded Programme on Immunization, and to students in two classes of primary
      schools. METHODS: ITN ownership and access were evaluated through two cross
      sectional surveys, conducted at baseline in April 2012, 11-15 months after the
      mass campaign, and at endline in December 2013, after 1 year of continuous
      distribution. A representative sample was obtained using a multi-stage cluster
      sampling design. Household heads were interviewed using a structured
      questionnaire. RESULTS: Household ownership of at least one ITN was 91.3% (95% CI
      88.8-93.9) at baseline and was not statistically significant at endline 18 months
      later at 88.3% (95% CI 84.9-91.0) (p = 0.10). Ownership of at least 1 ITN per two
      people significantly decreased from 51.3% (95% CI 47.1-55.4) to 40.2% (95% CI
      36.4-44.6) (p < 0.01). Population access to an ITN within the household also
      significantly decreased from 74.5% (95% CI 71.2-77.7) at baseline to 66.4% (95%
      CI 62.9-69.9) at endline (p < 0.01). The concentration index score for any CD
      channel was slightly positive (0.10; 95% CI 0.04-0.15). CONCLUSION: Thirty-one
      months after the mass campaign, the 15 months of continuous distribution
      activities had maintained levels of household ownership at least one ITN, but
      household ownership of one ITN for every two people and population access to ITN
      had declined. Ownership and access were higher with the CD programme than
      without. However, the number of ITNs delivered via ANC, CWC and two primary
      school classes were insufficient to sustain coverage targets. Future programmes
      should implement continuous distribution strategies fully within 1 year after a
      campaign or widen eligibility criteria (such as increase the number of classes)
      during the first year of implementation to make up for programme delays.

PMID- 29566677
TI  - Acidosis and acute kidney injury in severe malaria.
AB  - BACKGROUND: In severe falciparum malaria metabolic acidosis and acute kidney
      injury (AKI) are independent predictors of a fatal outcome in all age groups. The
      relationship between plasma acids, urine acids and renal function was
      investigated in adult patients with acute falciparum malaria. METHODS: Plasma and
      urinary acids which previously showed increased concentrations in proportion to
      disease severity in patients with severe falciparum malaria were quantified.
      Patients with uncomplicated malaria, sepsis and healthy volunteers served as
      comparator groups. Multiple regression and multivariate analysis were used to
      assess the relationship between organic acid concentrations and clinical
      syndromes, in particular AKI. RESULTS: Patients with severe malaria (n = 90),
      uncomplicated malaria (n = 94), non-malaria sepsis (n = 19), and healthy
      volunteers (n = 61) were included. Univariate analysis showed that both plasma
      and creatinine-adjusted urine concentrations of p-hydroxyphenyllactic acid
      (pHPLA) were higher in severe malaria patients with AKI (p < 0.001). Multiple
      regression analysis, including plasma or creatinine-adjusted urinary acids, and
      PfHRP2 as parasite biomass marker as independent variables, showed that pHPLA was
      independently associated with plasma creatinine (beta = 0.827) and urine
      creatinine (beta = 0.226). Principal component analysis, including four plasma
      acids and seven urinary acids separated a group of patients with AKI, which was
      mainly driven by pHPLA concentrations. CONCLUSIONS: Both plasma and urine
      concentrations of pHPLA closely correlate with AKI in patients with severe
      falciparum malaria. Further studies will need to assess the potential nephrotoxic
      properties of pHPLA.

PMID- 29566679
TI  - The in vitro estrogenic activity of the crude drugs found in Japanese herbal
      medicines prescribed for menopausal syndrome was enhanced by combining them.
AB  - BACKGROUND: Japanese herbal medicines can be used as alternatives to estrogen
      therapy and are sometimes prescribed for menopausal syndrome because they have
      fewer side effects and are associated with better compliance than estrogen
      therapy, but little is known about the pharmacological mechanisms of such
      treatments. This study aimed to explore the mechanisms responsible for the
      estrogen-like effects of five widely prescribed Japanese herbal medicines
      (unkeito, kamishoyosan, nyoshinsan, keishibukuryogan, and tokishakuyakusan).
      METHODS: We evaluated the estrogenic activity of these five Japanese herbal
      medicines and their metabolites using an estrogen receptor (ER)-dependent cell
      proliferation bioassay and an ER-dependent reporter assay. We also investigated
      the estrogenic activity of the crude drugs within the medicines and attempted to
      detect inter-crude drug synergistic effects using the ER-dependent reporter
      assay. RESULTS: We found that unkeito, kamishoyosan, and nyoshinsan exhibited
      estrogenic activity, and they displayed stronger estrogenic activity after being
      metabolized. Then, we focused on investigating the estrogenic activity of the
      crude drugs present within unkeito. We found that glycyrrhizae radix, cinnamomi
      cortex, evodiae fructus, and zingiberis rhizoma demonstrated ERbeta-dependent
      estrogenic activity. The combined use of evodiae fructus and glycyrrhizae radix,
      or evodiae fructus and cinnamomi cortex produced synergistic ERbeta-dependent
      estrogenic activity. CONCLUSION: It was suggested that unkeito, kamishoyosan, and
      nyoshinsan exert estrogenic activity, and hence, might be useful for treating
      menopausal syndrome. Furthermore, synergistic estrogenic effects were detected
      between some of the crude drugs present within unkeito.

PMID- 29566680
TI  - Process evaluations of task sharing interventions for perinatal depression in low
      and middle income countries (LMIC): a systematic review and qualitative meta
      synthesis.
AB  - BACKGROUND: Perinatal depression is common in low and middle income countries
      (LAMICs). Task sharing interventions have been implemented to treat perinatal
      depression in these settings, as a way of dealing with staff shortages. Task
      sharing allows lay health workers to provide services for less complex cases
      while being trained and supervised by specialists. Randomized controlled trials
      suggest that these interventions can be effective but there is limited
      qualitative information exploring barriers and facilitators to their
      implementation. This systematic review aims to systematically review current
      qualitative evidence of process evaluations of task sharing interventions for
      perinatal depression in LAMICs in relation to the United Kingdom (UK) Medical
      Research Council (MRC) framework for conducting process evaluations. METHODS: We
      searched Medline/ PubMed, PsycINFO, Scopus, Cochrane Library and Web of science
      for studies from LAMICS using search terms under the broad categories of: (a)
      "maternal depression'" (b) "intervention" (c) "lay counsellor" OR "community
      health worker" OR "non-specialist" and (d) "LAMICs". Abstracts were independently
      reviewed for inclusion by two authors. Full text articles were screened and data
      for included articles were extracted using a standard data extraction sheet.
      Qualitative synthesis of qualitative evidence was conducted. RESULTS: 8420
      articles were identified from initial searches. Of these, 26 full text articles
      were screened for eligibility with only three studies meeting the inclusion
      criteria. Main findings revealed that participants identified the following
      crucial factors: contextual factors included physical location, accessibility and
      cultural norms. Implementation factors included acceptability of the intervention
      and characteristics of the personnel. Mechanisms included counsellor factors such
      as motivating and facilitating trust; intervention factors such as use of stories
      and visual aids, and understandability of the content; and participant factors
      such as shared experience, meeting learning needs, and meeting expectations.
      CONCLUSIONS: While task sharing has been suggested as an effective way of filling
      the treatment gap for perinatal depression, there is a paucity of qualitative
      research exploring barriers and facilitators to implementing these interventions.
      Qualitative process evaluations are crucial for the development of culturally
      relevant interventions.

PMID- 29566681
TI  - Mapping staff perspectives towards the delivery of hospital care for children and
      young people with and without learning disabilities in England: a mixed methods
      national study.
AB  - BACKGROUND: Children and young people (CYP) with learning disabilities (LD) are a
      vulnerable population with increased risk of abuse and accidental injury and
      whose parents have reported concerns about the quality, safety and accessibility
      of their hospital care. The Care Quality Commission's (CQC) view of best practice
      for this group of patients includes: access to senior LD nurse provision; a
      clearly visible flagging system for identifying them; the use of hospital
      passports; and defined communication strategies (Glasper, Comp Child Adolesc Nurs
      40:63-67, 2017). What remains unclear is whether these recommendations are being
      applied and if so, what difference they are making. Furthermore, what we do not
      know is whether parental concerns of CYP with LD differ from parents of other
      children with long-term conditions. The aims of this study were to 1) describe
      the organisational context for healthcare delivery to CYP with LD and their
      families and 2) compare staff perceptions of their ability to identify the needs
      of CYP with and without LD and their families and provide high quality care to
      effectively meet these needs. METHODS: Individual interviews (n = 65) and
      anonymised online survey (n = 2261) were conducted with hospital staff working
      with CYP in 15 children's and 9 non-children's hospitals in England. The majority
      of interviews were conducted over the telephone and recorded and transcribed
      verbatim. Health Research Authority was obtained and verbal or written consent
      for data collection was obtained from all interview participants. RESULTS: The
      nature and extent of organisational policies, systems and practices in place
      within hospitals to support the care of CYP with LD differs across England and
      some uncertainty exists within and across hospitals as to what is currently
      available and accessed. Staff perceived that those with LD were included less,
      valued less, and less safe than CYP without LD. They also reported having less
      confidence, capability and capacity to meet the needs of this population compared
      to those without LD. CONCLUSION: Findings indicate inequality with regards the
      provision of high quality hospital care to children and young people with LD that
      meets their needs. There is a pressing need to understand the impact this has on
      them and their families. TRIAL REGISTRATION: The study has been registered on the
      NIHR CRN portfolio 20461 (Phase 1), 31336 (Phases 2-4).

PMID- 29566682
TI  - Investigating insecticide resistance and knock-down resistance (kdr) mutation in
      Dielmo, Senegal, an area under long lasting insecticidal-treated nets universal
      coverage for 10 years.
AB  - BACKGROUND: The use of insecticides, through indoor residual spraying and long
      lasting insecticide-treated nets (LLINs), is essential to control malaria
      vectors. However, the sustainability of these tools is challenged by the spread
      of insecticide resistance in Anopheles mosquitoes. This study was conducted to
      assess the susceptibility to insecticides and to determine the resistance
      mechanisms in malaria vectors in Dielmo, a rural area of western Senegal where
      LLINs were introduced a decade ago. METHODS: CDC bottle bioassays were used to
      determine the susceptibility of 2-5 day-old unfed Anopheles gambiae s.l. females
      to alphacypermethrin (12.5 ug/bottle), deltamethrin (12.5 ug/bottle), etofenprox
      (12.5 ug/bottle), lambdacyhalothrin (12.5 ug/bottle), permethrin (21.5
      ug/bottle), DDT (100 ug/bottle), bendiocarb (12.5 ug/bottle), pirimiphos-methyl
      (20 ug/bottle) and fenitrothion (50 ug/bottle). The involvement of glutathione-S
      transferases (GSTs) in insecticide resistance was assessed using a synergist,
      etacrynic acid (EA, 80 ug/bottle). Polymerase chain reaction (PCR) was used to
      investigate the presence of 'knock-down resistance (kdr)' mutation and to
      identify sibling species within the An. gambiae complex. RESULTS: CDC bottle
      bioassays showed that mosquitoes were fully susceptible to lambdacyhalothrin,
      bendiocarb and fenitrothion. Overall, mortality rates of 97, 94.6, 93.5, 92.1,
      and 90.1% were, respectively, observed for permethrin, deltamethrin, pirimiphos
      methyl, etofenprox and alphacypermethrin. Resistance to DDT was observed, with a
      mortality rate of 62%. The use of EA significantly improved the susceptibility of
      An. gambiae s.l. to DDT by inhibiting GSTs (p = 0.03). PCR revealed that
      Anopheles arabiensis was the predominant species (91.3%; IC 95 86.6-94%) within
      An. gambiae complex from Dielmo, followed by Anopheles coluzzii (5.4%; IC 95 2.7
      8.1%) and Anopheles gambiae s.s. (3.3%; IC 95 0.6-5.9%). Both 1014F and 1014S
      alleles were found in An. arabiensis population with frequencies of 0.08 and
      0.361, respectively, and 0.233 and 0.133, respectively in An. coluzzii. In An.
      gambiae s.s. population, only kdr L1014F mutation was detected, with a frequency
      of 0.167. It was observed that some individual mosquitoes carried both alleles,
      with 19 specimens recorded for An. arabiensis and 2 for An. coluzzii. The
      presence of L1014F and L1014S alleles were not associated with resistance to
      pyrethroids and DDT in An. arabiensis. CONCLUSIONS: The co-occurrence of 1014F
      and 1014S alleles and the probable involvement of GSTs enzymes in insecticide
      resistance in An. gambiae s.l. should prompt the local vector programme to
      implement non-pyrethroid/DDT insecticides alternatives.

PMID- 29566683
TI  - Population pharmacokinetic and pharmacodynamic properties of artesunate in
      patients with artemisinin sensitive and resistant infections in Southern Myanmar.
AB  - BACKGROUND: Artemisinins are the most effective anti-malarial drugs for
      uncomplicated and severe Plasmodium falciparum malaria. However, widespread
      artemisinin resistance in the Greater Mekong Region of Southeast Asia is
      threatening the possibility to control and eliminate malaria. This work aimed to
      evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its
      active metabolite, dihydroartemisinin, in patients with sensitive and resistant
      falciparum infections in Southern Myanmar. In addition, a simple nomogram
      previously developed to identify artemisinin resistant malaria infections was
      evaluated. METHODS: Fifty-three (n = 53) patients were recruited and received
      daily oral artesunate monotherapy (4 mg/kg) for 7 days. Frequent artesunate and
      dihydroartemisinin plasma concentration measurements and parasite microscopy
      counts were obtained and evaluated using nonlinear mixed-effects modelling.
      RESULTS: The absorption of artesunate was best characterized by a transit
      compartment (n = 3) model, followed by one-compartment disposition models for
      artesunate and dihydroartemisinin. The drug-dependent parasite killing effect of
      dihydroartemisinin was described using an Emax function, with a mixture model
      discriminating between artemisinin sensitive and resistant parasites. Overall,
      56% of the studied population was predicted to have resistant malaria infections.
      Application of the proposed nomogram to identify artemisinin-resistant malaria
      infections demonstrated an overall sensitivity of 90% compared to 55% with the
      traditional day-3 positivity test. CONCLUSION: The pharmacokinetic
      pharmacodynamic properties of artesunate and dihydroartemisinin were well
      characterized with a mixture model to differentiate between drug sensitive and
      resistant infections in these patients. More than half of all patients recruited
      in this study had artemisinin-resistant infections. The relatively high
      sensitivity of the proposed nomogram highlights its potential clinical
      usefulness.

PMID- 29566684
TI  - Effect of peer support interventions on cardiovascular disease risk factors in
      adults with diabetes: a systematic review and meta-analysis.
AB  - BACKGROUND: Peer support by persons affected with diabetes improves peer
      supporter's diabetes self-management skills. Peer support interventions by
      individuals who have diabetes or are affected by diabetes have been shown to
      improve glycemic control; however, its effects on other cardiovascular disease
      risk factors in adults with diabetes are unknown. We aimed to estimate the effect
      of peer support interventions on cardiovascular disease risk factors other than
      glycemic control in adults with diabetes. METHODS: We conducted a systematic
      review and meta-analysis of randomized controlled trials comparing peer support
      interventions to a control condition in adults affected by diabetes that measured
      any cardiovascular disease risk factors [Body Mass Index, smoking, diet, physical
      activity, cholesterol level, glucose control and blood pressure]. Quality was
      assessed by Cochrane's risk of bias tool. We calculated standardized mean
      difference effect sizes using random effects models. RESULTS: We retrieved 438
      citations from multiple databases including OVID MEDLINE, Cochrane database and
      Scopus, and author searches. Of 233 abstracts reviewed, 16 articles met inclusion
      criteria. A random effects model in a total of 3243 participants showed a
      positive effect of peer support interventions on systolic BP with a pooled effect
      size of 2.07 mmHg (CI 0.35 mmHg to 3.79 mmHg, p = 0.02); baseline pooled systolic
      blood pressure was 137 mmHg. There was a non-significant effect of peer support
      interventions on diastolic blood pressure, cholesterol, body mass index, diet and
      physical activity. Cardiovascular disease risk factors other than glycemic
      control outcomes were secondary outcomes in most studies and baseline values were
      normal or mildly elevated. Only one study reported smoking outcomes. CONCLUSIONS:
      We found a small (2 mmHg) positive effect of peer support interventions on
      systolic blood pressure in adults with diabetes whose baseline blood pressure was
      on average minimally elevated. Additional studies need to be conducted to further
      understand the effect of peer support interventions on high-risk cardiovascular
      disease risk factors in adults with diabetes.

PMID- 29566685
TI  - Polymorphisms analysis of the Plasmodium ovale tryptophan-rich antigen gene
      (potra) from imported malaria cases in Henan Province.
AB  - BACKGROUND: Plasmodium ovale has two different subspecies: P. ovale curtisi and
      P. ovale wallikeri, which may be distinguished by the gene potra encoding P.
      ovale tryptophan-rich antigen. The sequence and size of potra gene was variable
      between the two P. ovale spp., and more fragment sizes were found compared to
      previous studies. Further information about the diversity of potra genes in these
      two P. ovale spp. will be needed. METHODS: A total of 110 dried blood samples
      were collected from the clinical patients infected with P. ovale, who all
      returned from Africa in Henan Province in 2011-2016. The fragments of potra were
      amplified by nested PCR. The sizes and species of potra gene were analysed after
      sequencing, and the difference between the isolates were analysed with the
      alignment of the amino acid sequences. The phylogenetic tree was constructed by
      neighbour-joining to determine the genetic relationship among all the isolates.
      The distribution of the isolates was analysed based on the origin country.
      RESULTS: Totally 67 samples infected with P. o. wallikeri, which included 8
      genotypes of potra, while 43 samples infected with P. o. curtisi including 3
      genotypes of potra. Combination with the previous studies, P. o. wallikeri had
      six sizes, 227, 245, 263, 281, 299 and 335 bp, and P. o. curtisi had four sizes,
      299, 317, 335 and 353 bp, the fragment sizes of 299 and 335 bp were the overlaps
      between the two species. Six amino acid as one unit was firstly used to analyse
      the amino acid sequence of potra. Amino acid sequence alignment revealed that
      potra of P. o. wallikeri differed in two amino acid units, MANPIN and AITPIN,
      while potra of P. o. curtisi differed in amino acid units TINPIN and TITPIS.
      Combination with the previous studies, there were ten subtypes of potra exiting
      for P. o. wallikeri and four subtypes for P. o. curtisi. The phylogenetic tree
      showed that 11 isolates were divided into two clusters, P. o. wallikeri which was
      then divided into five sub-clusters, and P. o. curtisi which also formed two sub
      clusters with their respective reference sequences. The genetic relationship of
      the P. ovale spp. mainly based on the number of the dominant amino acid repeats,
      the number of MANPIN, AITPIN, TINPIN or TITPIS. The genotype of the 245 bp size
      for P. o. wallikeri and that of the 299 and 317 bp size for P. o. curtisi were
      commonly exiting in Africa. CONCLUSION: This study further proved that more
      fragment sizes were found, P. o. wallikeri had six sizes, P. o. curtisi had four
      sizes. There were ten subtypes of potra exiting for P. o. wallikeri and four
      subtypes for P. o. curtisi. The genetic polymorphisms of potra provided
      complementary information for the gene tracing of P. ovale spp. in the malaria
      elimination era.

PMID- 29566686
TI  - Synthesis of avenanthramides using engineered Escherichia coli.
AB  - BACKGROUND: Hydroxycinnamoyl anthranilates, also known as avenanthramides (avns),
      are a group of phenolic alkaloids with anti-inflammatory, antioxidant, anti-itch,
      anti-irritant, and antiatherogenic activities. Some avenanthramides (avn A-H and
      avn K) are conjugates of hydroxycinnamic acids (HC), including p-coumaric acid,
      caffeic acid, and ferulic acid, and anthranilate derivatives, including
      anthranilate, 4-hydroxyanthranilate, and 5-hydroxyanthranilate. Avns are
      primarily found in oat grain, in which they were originally designated as
      phytoalexins. Knowledge of the avns biosynthesis pathway has now made it possible
      to synthesize avns through a genetic engineering strategy, which would help to
      further elucidate their properties and exploit their beneficial biological
      activities. The aim of the present study was to synthesize natural avns in
      Escherichia coli to serve as a valuable resource. RESULTS: We synthesized nine
      avns in E. coli. We first synthesized avn D from glucose in E. coli harboring
      tyrosine ammonia lyase (TAL), 4-coumarate:coenzyme A ligase (4CL), anthranilate N
      hydroxycinnamoyl/benzoyltransferase (HCBT), and anthranilate synthase (trpEG). A
      trpD deletion mutant was used to increase the amount of anthranilate in E. coli.
      After optimizing the incubation temperature and cell density, approximately 317.2
      mg/L of avn D was synthesized. Avn E and avn F were then synthesized from avn D,
      using either E. coli harboring HpaBC and SOMT9 or E. coli harboring HapBC alone,
      respectively. Avn A and avn G were synthesized by feeding 5-hydroxyanthranilate
      or 4-hydroxyanthranilate to E. coli harboring TAL, 4CL, and HCBT. Avn B, avn C,
      avn H, and avn K were synthesized from avn A or avn G, using the same approach
      employed for the synthesis of avn E and avn F from avn D. CONCLUSIONS: Using
      different HCs, nine avns were synthesized, three of which (avn D, avn E, and avn
      F) were synthesized from glucose in E. coli. These diverse avns provide a
      strategy to synthesize both natural and unnatural avns, setting a foundation for
      exploring the biological activities of diverse avns.

PMID- 29566687
TI  - "It was the whole picture" a mixed methods study of successful components in an
      integrated wellness service in North East England.
AB  - BACKGROUND: A growing number of Local Authorities (LAs) have introduced
      integrated wellness services as part of efforts to deliver cost effective,
      preventive services that address the social determinants of health. This study
      examined which elements of an integrated wellness service in the north east of
      England were effective in improving health and wellbeing (HWB). METHODS: The
      study used a mixed-methods approach. In-depth semi-structured interviews (IVs)
      were conducted with integrated wellness service users (n = 25) and focus groups
      (FGs) with group based service users (n = 14) and non-service users (n = 23) to
      gather the views of stakeholders. Findings are presented here alongside analysis
      of routine monitoring data. The different data were compared to examine what each
      data source revealed about the effectiveness of the service. RESULTS: Findings
      suggest that integrated wellness services work by addressing the social
      determinants of health and respond to multiple complex health and social concerns
      rather than single issues. The paper identifies examples of 'active ingredients'
      at the heart of the programme, such as sustained relationships, peer support and
      confidence building, as well as the activities through which changes take place,
      such as sports and leisure opportunities which in turn encourage social
      interaction. Wider wellbeing outcomes, including reduced social isolation and
      increased self-efficacy are also reported. Practical and motivational support
      helped build community capacity by encouraging community groups to access
      funding, helped navigate bureaucratic systems, and promoted understanding of
      marginalised communities. Fully integrated wellness services could support
      progression opportunities through volunteering and mentoring. CONCLUSIONS: An
      integrated wellness service that offers a holistic approach was valued by service
      users and allowed them to address complex issues simultaneously. Few of the
      reported health gains were captured in routine data. Quantitative and qualitative
      data each offered a partial view of how effectively services were working.

PMID- 29566688
TI  - Implementation of knowledge-based palliative care in nursing homes and pre-post
      post evaluation by cross-over design: a study protocol.
AB  - BACKGROUND: The demography of the world is changing as the population is ageing.
      Because of this change to a higher proportion of older people, the WHO has called
      for improved palliative care for older persons. A large number of all deaths in
      the industrialised world occur while older people are living in nursing homes and
      therefore a key question becomes how the principles of palliative care can be
      implemented in that context. The aims of this study are: a) to describe a model
      of an educational intervention with the goal of implementing knowledge-based
      palliative care in nursing homes, and b) to describe the design of the evaluation
      of the effectiveness regarding the implementation of knowledge-based palliative
      care. METHODS/DESIGN: A complex intervention is evaluated by means of a cross
      over design. An educational intervention concerning palliative care consisting of
      five seminars during 6 months for staff and managers has been developed and
      conducted in 20 nursing homes in two counties. Before the intervention started,
      the feasibility was tested in a pilot study conducted in nursing homes not
      included in the main study. The intervention is evaluated through a non
      randomized experimental design with intervention and control groups and pre- and
      post-assessments. The evaluation includes older persons living in nursing homes,
      next-of-kin, staff and managers. Data collection consists of quantitative methods
      such as questionnaires and register data and qualitative methods in the form of
      individual interviews, focus-group interviews and participant observations.
      DISCUSSION: The research will contribute to new knowledge about how to implement
      knowledge-based palliative care in a nursing home setting. A strength of this
      project is that the Medical Research Council framework of complex intervention is
      applied. The four recommended stages, Development, Feasibility and piloting,
      Evaluation and Implementation, are combined for the educational intervention,
      which functions as a strategy to achieve knowledge-based palliative care in the
      nursing homes. Implementation is always a question of change and a good
      theoretical understanding is needed for drawing valid conclusions about the
      causal mechanisms of change. The topic is highly relevant considering the world's
      ageing population. The data collection is completed and the analysis is ongoing.
      TRIAL REGISTRATION: NCT02708498 .

PMID- 29566689
TI  - Brain injury rehabilitation after road trauma in new South Wales, Australia -
      insights from a data linkage study.
AB  - BACKGROUND: Population-based patterns of care studies are important for trauma
      care but conducting them is expensive and resource-intensive. Linkage of
      routinely collected administrative health data may provide an efficient
      alternative. The aims of this study are to describe the rehabilitation pathway
      for trauma survivors and to analyse the brain injury rehabilitation outcomes in
      the two care settings (specialist brain injury and non-specialist general
      rehabilitation units). METHODS: This is an observational study using routinely
      collected registry data (New South Wales Trauma Registry linked with the
      Australasian Rehabilitation Outcomes Centre Inpatient Dataset). The study cohort
      includes 268 road trauma patients who were admitted to trauma services between
      2009 and 2012 and received inpatient rehabilitation because of a brain injury.
      RESULTS: Of those who need inpatient rehabilitation, 62% (n = 166) were admitted
      to specialist units with the remainder (n = 102) admitted to non-specialist
      units. Those admitted to a specialist units were younger (p < 0.001), had a lower
      cognitive FIM score (p = 0.003) on admission than those admitted to non
      specialist units. Specialist units achieved better overall FIM score improvements
      from admission to discharge (43 vs 30 points, p > 0.001) but at a cost of longer
      length of stay (median 47 vs 24 days, p < 0.001). There were very few discharges
      to residential aged care facilities from rehabilitation (2% in non-specialist
      units and none from specialist units). There was a long time lag between trauma
      and admission to inpatient rehabilitation with only a quarter of the patients
      admitted to a specialist unit by end of week four. Few older patients (19%) with
      brain injury were admitted to specialist units. CONCLUSIONS: It is feasible to
      use routinely collected registry data to monitor inpatient rehabilitation
      outcomes of trauma care. There were differences in characteristics and outcomes
      of patients with traumatic brain injury admitted to specialist units compared
      with non-specialist units.

PMID- 29566690
TI  - Use of chitin and chitosan to produce new chitooligosaccharides by chitinase
      Chit42: enzymatic activity and structural basis of protein specificity.
AB  - BACKGROUND: Chitinases are ubiquitous enzymes that have gained a recent
      biotechnological attention due to their ability to transform biological waste
      from chitin into valued chito-oligomers with wide agricultural, industrial or
      medical applications. The biological activity of these molecules is related to
      their size and acetylation degree. Chitinase Chit42 from Trichoderma harzianum
      hydrolyses chitin oligomers with a minimal of three N-acetyl-D-glucosamine
      (GlcNAc) units. Gene chit42 was previously characterized, and according to its
      sequence, the encoded protein included in the structural Glycoside Hydrolase
      family GH18. RESULTS: Chit42 was expressed in Pichia pastoris using fed-batch
      fermentation to about 3 g/L. Protein heterologously expressed showed similar
      biochemical properties to those expressed by the natural producer (42 kDa, optima
      pH 5.5-6.5 and 30-40  degrees C). In addition to hydrolyse colloidal chitin, this
      enzyme released reducing sugars from commercial chitosan of different sizes and
      acetylation degrees. Chit42 hydrolysed colloidal chitin at least 10-times more
      efficiently (defined by the kcat/Km ratio) than any of the assayed chitosan.
      Production of partially acetylated chitooligosaccharides was confirmed in
      reaction mixtures using HPAEC-PAD chromatography and mass spectrometry. Masses
      corresponding to (D-glucosamine)1-8-GlcNAc were identified from the hydrolysis of
      different substrates. Crystals from Chit42 were grown and the 3D structure
      determined at 1.8 A resolution, showing the expected folding described for other
      GH18 chitinases, and a characteristic groove shaped substrate-binding site, able
      to accommodate at least six sugar units. Detailed structural analysis allows
      depicting the features of the Chit42 specificity, and explains the chemical
      nature of the partially acetylated molecules obtained from analysed substrates.
      CONCLUSIONS: Chitinase Chit42 was expressed in a heterologous system to levels
      never before achieved. The enzyme produced small partially acetylated
      chitooligosaccharides, which have enormous biotechnological potential in medicine
      and food. Chit42 3D structure was characterized and analysed. Production and
      understanding of how the enzymes generating bioactive chito-oligomers work is
      essential for their biotechnological application, and paves the way for future
      work to take advantage of chitinolytic activities.

PMID- 29566691
TI  - Use of a public-private partnership in malaria elimination efforts in Sri Lanka;
      a case study.
AB  - BACKGROUND: In special circumstances, establishing public private partnerships
      for malaria elimination may achieve targets faster than the state sector acting
      by itself. Following the end of the separatist war in Sri Lanka in 2009, the Anti
      Malaria Campaign (AMC) of Sri Lanka intensified malaria surveillance jointly with
      a private sector partner, Tropical and Environmental Diseases and Health
      Associates Private Limited (TEDHA) with a view to achieving malaria elimination
      targets by 2014. METHODS: This is a case study on how public private partnerships
      can be effectively utilized to achieve malaria elimination goals. TEDHA
      established 50 Malaria Diagnostic Laboratories and 17 entomology surveillance
      sentinel sites in consultation with the AMC in areas difficult to access by
      government officials (five districts in two provinces affected by war). RESULTS:
      TEDHA screened 994,448 individuals for malaria, of which 243,867 were screened at
      mobile malaria clinics as compared to 1,102,054 screened by the AMC. Nine malaria
      positives were diagnosed by TEDHA, while the AMC diagnosed 103 malaria cases in
      the same districts in parallel. Over 13,000 entomological activity days were
      completed. Relevant information was shared with AMC and the data recorded in the
      health information system. CONCLUSIONS: A successful public-private partnership
      model for malaria elimination was initiated at a time when the health system was
      in disarray in war ravaged areas of Sri Lanka. This ensured a high annual blood
      examination rate and screening of vulnerable people in receptive areas. These
      were important for certification of malaria-free status which Sri Lanka
      eventually received in 2016.

PMID- 29566692
TI  - Geographic assessment of access to health care in patients with cardiovascular
      disease in South Africa.
AB  - BACKGROUND: Noncommunicable diseases (NCDs) including cardiovascular diseases
      (CVDs), diabetes, cancer and chronic lung disease are increasingly emerging as
      major contributors to morbidity and mortality in developing countries. For
      example, in South Africa, 195 people died per day between 1997 and 2004 from CVDs
      related causes. Access to efficient and effective health facility and care is an
      important contributing factor to overall population health and addressing
      prognosis, care and management CVD disease burden. This study aimed to spatially
      evaluate geographic health care access of people diagnosed with CVD to health
      facilities and to evaluate the density of the existing health facility network in
      South Africa. METHODS: Data was obtained from the National Income Dynamics Study
      (NIDS) conducted in 4 waves (phases) between 2008 and 2014. The participants who
      responded as having heart problems that were diagnosed by a health practitioner
      were extracted for use in this study. Network analyst in ArcGIS (r) was used to
      generate a least-cost path, which refers to the best path that one can travel.
      The residential locations of participants diagnosed with heart problems were put
      into the network analysis model as origins and the location of health facilities
      were destinations. District averages were used to protect the identity of studied
      participants. RESULTS: There were a total of 51, 42, 43, 43 health districts out
      the 52 that had recorded subjects with a heart condition in the 2008, 2010-2011,
      2012 and 2014-2015 waves, respectively. The mean distance from a case household
      to a health facility per wave was 2, 2.3, 2.1 and 2.1 km in 2008, 2010-2011 and
      2014-2015 respectively. The maximum individual distances travelled per wave were
      41.4 km, 40,5 km, 44,2 km and 39.6 km for the 2008, 2010-2011, 2012 and 2014-2015
      waves respectively. For district level analysis, participants with CVD residing
      in the districts found to be among the poorest in the country travelled the
      longest distances. These were located in the provinces of Limpopo and KwaZulu
      Natal. It was also found that districts with large proportions of their
      population living in rural settings had among the lowest densities of health
      facilities. Significant percentages of study participants were exposed to
      numerous CVD risk factors, the commonly reported one being high blood pressure. A
      lack of regular exercise was also commonly reported in each of the waves.
      CONCLUSION: A lack of accessible healthcare in already impoverished
      municipalities could result in an increase lack of timely diagnosis, CVD case
      management. This could result in increased CVD-related morbidity and mortality.
      GIS methods have the potential to assist national health programs to develop
      policies that target issues such as areas or populations being underserved by
      health facilities and populations that must travel long distances to receive
      healthcare. These policies will be key in preventing and controlling the emerging
      CVD burden through an accessible primary healthcare system for early detection
      and case management.

PMID- 29566693
TI  - Potentiating and synergistic effect of grapefruit juice on the antioxidant and
      anti-inflammatory activity of aripiprazole against hydrogen peroxide induced
      oxidative stress in mice.
AB  - BACKGROUND: Dependence on antipsycotic drugs like aripriprazole (ARI) is
      increasing at alarming rate, hence, this study was undertaken to support the
      hypothesis that supplementation of Citrus paradisi (Grapefruit) juice having high
      concentration of polyphenols might potentiate and synergize the therapeutic
      effect of ARI, by increasing its bioavailability and inherent antioxidant
      potential. These benefits together might decrease the daily dosage of the ARI and
      thus alleviate the possible side effects of drug. METHODS: In this study the
      antioxidant and anti-inflammatory potential of ARI alone and in combination with
      GFJ was evaluated for hydrogen peroxide (H2O2) induced oxidative stress in mice.
      Seventy mice (4 weeks old), were randomly divided into seven groups. Group I:
      Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated;
      Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI,
      GFJ and H2O2 treated. Serum levels of alanine aminotransferase (ALT), blood urea
      nitrogen (BUN), creatinine kinase (CK), creatinine and total protein were
      measured. Furthermore, pro-inflammatory cytokines Interleukin (IL)-1alpha, IL-2,
      IL-10 and tumor necrosis factor-alpha (TNF-alpha) concentrations were also
      measured. RESULTS: The mice group that was treated with ARI, GFJ or combination
      of the two showed significant improvement in the H2O2 altered parameters with the
      combination group showing more significant improvement than the ARI and GFJ alone
      groups indicating a synergistic and potentiating effect of the antioxidant and
      anti-inflammatory potential of GFJ on ARI. CONCLUSION: Supplementing GFJ to ARI
      might increase an anti-oxidative potential of ARI due to inherent antioxidant and
      anti-inflammatory activity of GFJ and thus could alleviate the possible dosage
      dependent side effects of ARI.

PMID- 29566694
TI  - 4-Acetylantroquinonol B inhibits lipopolysaccharide-induced cytokine release and
      alleviates sepsis through of MAPK and NFkappaB suppression.
AB  - BACKGROUND: Antrodia cinnamomea is an indigenous medicinal mushroom in Taiwan,
      commonly used for the treatment of cancers and inflammatory disorders. 4
      acetylantroquinonol B (4AAQB) is one of the active component isolated from the
      mycelium of A. cinnamomea. However, whether 4AAQB exhibits anti-inflammatory
      effect is not clear. METHODS: The anti-inflammatory activity of 4AAQB was
      examined by ELISA to measure the pro-inflammatory cytokines production in
      lipopolysaccharide (LPS)-simulated RAW264.7 cells, peritoneal macrophages and in
      mice. The effect of 4AAQB for MAPK kinase molecules phosphorylation in LPS
      stimulated RAW264.7 macrophage including ERK, JNK and p38 were evaluated. The in
      vivo efficacy of 4AAQB was also demonstrated. RESULTS: In the present study, we
      found that 4AAQB exhibits anti-inflammatory effects inhibit tumor necrosis factor
      alpha (TNF-alpha)/interleukin-6 (IL-6) releasing and LPS-stimulated phagocytes
      migration without affect cell growth. In addition, the MAPK kinase molecules
      phosphorylation in LPS-stimulated RAW264.7 macrophage including ERK, JNK and p38
      was inhibited by 4AAQB. The phosphorylation of NFkappaB subunit p65 and IkBalpha
      were also decreased after 4AAQB treatment. Furthermore, 4AAQB attenuates the
      cytokine production in LPS-induced and CLP-induced septic mice. CONCLUSION: These
      results showed that 4AAQB exhibited anti-inflammatory property both in vitro and
      in vivo, suggesting that 4AAQB may be a therapeutic candidate which used in
      inflammatory disorders treatment.

PMID- 29566695
TI  - Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric
      cerebral malaria.
AB  - BACKGROUND: Cerebral malaria (CM) causes a rapidly developing coma, and remains a
      major contributor to morbidity and mortality in malaria-endemic regions. This
      study sought to determine the relationship between cerebrospinal fluid (CSF)
      Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory
      and radiographic features in a cohort of children with retinopathy-positive CM.
      METHODS: Patients included in the study were admitted (2009-2013) to the
      Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi)
      meeting World Health Organization criteria for CM with findings of malarial
      retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and
      CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression
      analysis assessed the association of clinical and radiographic characteristics
      with the primary outcome of death during hospitalization. RESULTS: In this cohort
      of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%)
      patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during
      hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF
      PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable
      analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00,
      95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio
      2.05, 95% confidence interval 0.45-9.35). CONCLUSIONS: Elevation of CSF, but not
      plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2
      egress into the CSF may represent alteration of blood brain barrier permeability
      related to the sequestration of parasitized erythrocytes in the cerebral
      microvasculature.

PMID- 29566696
TI  - How do NHS organisations plan research capacity development? Strategies,
      strengths, and opportunities for improvement.
AB  - Research that is integral into a 'learning healthcare system' can promote cost
      effective services and knowledge creation. As such, research is defined as a
      'core function' in UK health service organisations, and is often planned through
      research and development (R&D) strategies that aim to promote research activity
      and research capacity development (RCD). The discussion focuses around the
      content of ten R&D strategies for healthcare organisations in England and
      Scotland, with respect to RCD. These organisations were engaged with a research
      interest network called ACORN (Addressing Organisational Capacity to do Research
      Network) that included two Scottish Health Boards, four community and mental
      health trusts, two provincial district hospitals, and two teaching hospitals. We
      undertook a thematic documentary analysis of the R&D strategies which identified
      11 'core activities' of RCD. The potential for building research capacity in
      these 'core activities' was established by reviewing them through the lens of a
      RCD framework. Core activities aimed to 'hard wire' RCD into health
      organisations. They demonstrated a complex interplay between developing a strong
      internal organisational infrastructure, and supporting individual career planning
      and skills development, in turn enabled by organisational processes. They also
      included activities to build stronger inter-organisational relationships and
      networks. Practitioner, manager and patient involvement was a cross cutting
      theme. The potential to demonstrate progress was included in plans through
      monitoring activity across all RCD principles. Strategies were primarily aimed at
      research production rather than research use. Developing 'actionable
      dissemination' was poorly addressed in the strategies, and represents an area for
      improvement. We describe strengths of RCD planning activities, and opportunities
      for improvement. We explore how national policy and research funders can
      influence health systems' engagement in research.

PMID- 29566697
TI  - 'Broken hospital windows': debating the theory of spreading disorder and its
      application to healthcare organizations.
AB  - BACKGROUND: Research in criminology and social-psychology supports the idea that
      visible signs of disorder, both physical and social, may perpetuate further
      disorder, leading to neighborhood incivilities, petty violations, and potentially
      criminal behavior. This theory of 'broken windows' has now also been applied to
      more enclosed environments, such as organizations. MAIN TEXT: This paper debates
      whether the premise of broken windows theory, and the concept of 'disorder',
      might also have utility in the context of health services. There is already a
      body of work on system migration, which suggests a role for violations and
      workarounds in normalizing unwarranted deviations from safe practices in
      healthcare organizations. Studies of visible disorder may be needed in
      healthcare, where the risks of norm violations and disorderly environments, and
      potential for harm to patients, are considerable. Everyday adjustments and
      flexibility is mostly beneficial, but in this paper, we ask: how might deviations
      from the norm escalate from necessary workarounds to risky violations in care
      settings? Does physical or social disorder in healthcare contexts perpetuate
      further disorder, leading to downstream effects, including increased risk of harm
      to patients? CONCLUSIONS: We advance a model of broken windows in healthcare, and
      a proposal to study this phenomenon.

PMID- 29566698
TI  - Effectiveness of an oral health intervention program for children with congenital
      heart defects.
AB  - BACKGROUND: Children with congenital heart defects (CHD) are reported to have
      poorer oral health compared with healthy children. The aim of the present study
      was to evaluate the effectiveness of an intensive oral health care program among
      children with CHD followed from infancy to the age of 5 years, by comparing their
      oral health status at 5 years with a control group of children with CHD who had
      not received the program. METHODS: In this longitudinal study, children in
      western Norway with a need for lifelong follow-up due to congenital heart defects
      were invited to participate (n = 119). Children born in 2008-2011 were offered an
      oral health intervention program from infancy to the age of 5 years. The outcome
      measures for evaluating the intervention were dental caries prevalence, dental
      erosion, plaque index and gingival bleeding index. The data of the intervention
      group were compared with cross sectional oral health data of 5 year old controls
      with CHD born 2005-2007 (already published). RESULTS: Early oral health
      intervention did not affect the prevalence of caries (25.3% versus 25.4%) or
      dental erosion (22.2% versus 19.7%) of children with CHD assessed at 5 years.
      Children in the intervention group were less likely than those in the control
      group to present with both dental plaque and gingival bleeding at age 5 years. In
      spite of no difference in caries prevalence between the groups, caries affected
      children (d1-5mft) in the intervention group had fewer teeth affected by caries
      than children in the control group (p = 0.06). The care index was reported to be
      higher in the intervention group compared with the control group, implying that
      fewer children in the intervention group suffered from untreated dentine caries.
      Parents in the intervention group were more likely to brush their children's
      teeth twice a day than parents of children in the control group. CONCLUSION: The
      oral health promotive program did not influence the prevalence of caries nor
      dental erosion. However, the findings indicated better oral hygiene, reduced
      gingival bleeding and less untreated dentine caries in the intervention compared
      with the control group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03311438 .
      Registration date: October 17th 2017, retrospectively registered.

PMID- 29566699
TI  - Integrative genomics identifies new genes associated with severe COPD and
      emphysema.
AB  - BACKGROUND: Genome-wide association studies have identified several genetic risk
      loci for severe chronic obstructive pulmonary disease (COPD) and emphysema.
      However, these studies do not fully explain disease heritability and in most
      cases, fail to implicate specific genes. Integrative methods that combine gene
      expression data with GWAS can provide more power in discovering disease
      associated genes and give mechanistic insight into regulated genes. METHODS: We
      applied a recently described method that imputes gene expression using reference
      transcriptome data to genome-wide association studies for two phenotypes (severe
      COPD and quantitative emphysema) and blood and lung tissue gene expression
      datasets. We further tested the potential causality of individual genes using
      multi-variant colocalization. RESULTS: We identified seven genes significantly
      associated with severe COPD, and five genes significantly associated with
      quantitative emphysema in whole blood or lung. We validated results in
      independent transcriptome databases and confirmed colocalization signals for
      PSMA4, EGLN2, WNT3, DCBLD1, and LILRA3. Three of these genes were not located
      within previously reported GWAS loci for either phenotype. We also identified
      genetically driven pathways, including those related to immune regulation.
      CONCLUSIONS: An integrative analysis of GWAS and gene expression identified novel
      associations with severe COPD and quantitative emphysema, and also suggested
      disease-associated genes in known COPD susceptibility loci. TRIAL REGISTRATION:
      NCT00608764 , Registry: ClinicalTrials.gov, Date of Enrollment of First
      Participant: November 2007, Date Registered: January 28, 2008 (retrospectively
      registered); NCT00292552 , Registry: ClinicalTrials.gov, Date of Enrollment of
      First Participant: December 2005, Date Registered: February 14, 2006
      (retrospectively registered).

PMID- 29566700
TI  - Review of 14 drowning publications based on the Utstein style for drowning.
AB  - BACKGROUND: The Utstein style for drowning (USFD) was published in 2003 with the
      aim of improving drowning research. To support a revision of the USFD, the
      current study aimed to generate an inventory of the use of the USFD parameters
      and compare the findings of the publications that have used the USFD. METHODS: A
      search in Pubmed, Embase, the Cochrane Library, Web of Science and Scopus was
      performed to identify studies that used the USFD and were published between 01-10
      2003 and 22-03-2015. We also searched in Pubmed, Embase, the Cochrane Library,
      Web of Science, and Scopus for all publications that cited the two publications
      containing the original ILCOR advisory statement introducing and recommending the
      USFD. In total we identified 14 publications by groups that explicitly used
      elements of the USFD for collecting and reporting their data. RESULTS: Of the 22
      core and 19 supplemental USFD parameters, 6-19 core (27-86%) and 1-12 (5-63%)
      supplemental parameters were used; two parameters (5%) have not been used in any
      publication. Associations with outcome were reported for nine core (41%) and five
      supplemental (26%) USFD parameters. The USFD publications also identified non
      USFD parameters related to outcome: initial cardiac rhythm, time points and
      intervals during resuscitation, intubation at the drowning scene, first hospital
      core temperature, serum glucose and potassium, the use of inotropic/vasoactive
      agents and the Paediatric Index of Mortality 2-score. CONCLUSIONS: Fourteen USFD
      based drowning publications have been identified. These publications provide
      valuable information about the process and quality of drowning resuscitation and
      confirm that the USFD is helpful for a structured comparison of the outcome of
      drowning resuscitation.

PMID- 29566701
TI  - Correction to: Social and environmental determinants of child health in Mongolia
      across years of rapid economic growth: 2000-2010.
AB  - Unfortunately, after publication of this article [1], it was noticed that an
      error during the production process resulted in an incorrect author name. The
      author Semira Manaseki-Holland is incorrectly displayed as Semira Manaseki
      Hollan. The full, corrected author list can be seen above.

PMID- 29566702
TI  - A new CFD based non-invasive method for functional diagnosis of coronary
      stenosis.
AB  - BACKGROUND: Accurate functional diagnosis of coronary stenosis is vital for
      decision making in coronary revascularization. With recent advances in
      computational fluid dynamics (CFD), fractional flow reserve (FFR) can be derived
      non-invasively from coronary computed tomography angiography images (FFRCT) for
      functional measurement of stenosis. However, the accuracy of FFRCT is limited due
      to the approximate modeling approach of maximal hyperemia conditions. To overcome
      this problem, a new CFD based non-invasive method is proposed. METHODS: Instead
      of modeling maximal hyperemia condition, a series of boundary conditions are
      specified and those simulated results are combined to provide a pressure-flow
      curve for a stenosis. Then, functional diagnosis of stenosis is assessed based on
      parameters derived from the obtained pressure-flow curve. RESULTS: The proposed
      method is applied to both idealized and patient-specific models, and validated
      with invasive FFR in six patients. Results show that additional hemodynamic
      information about the flow resistances of a stenosis is provided, which cannot be
      directly obtained from anatomy information. Parameters derived from the simulated
      pressure-flow curve show a linear and significant correlations with invasive FFR
      (r > 0.95, P < 0.05). CONCLUSION: The proposed method can assess flow resistances
      by the pressure-flow curve derived parameters without modeling of maximal
      hyperemia condition, which is a new promising approach for non-invasive
      functional assessment of coronary stenosis.

PMID- 29566703
TI  - Cognitive impairment in metabolically-obese, normal-weight rats: identification
      of early biomarkers in peripheral blood mononuclear cells.
AB  - BACKGROUND: Metabolically-obese, normal-weight (MONW) individuals are not obese
      in terms of weight and height but have a number of obesity-related features (e.g.
      greater visceral adiposity, insulin resistance, and increased risk of
      cardiovascular disease). The MONW phenotype is related to the intake of
      unbalanced diets, such as those rich in fat. Increasing evidence shows a
      relationship between high-fat diet consumption and mild cognitive impairment and
      dementia. Thus, MONW individuals could be at a greater risk of cognitive
      dysfunction. We aimed to evaluate whether MONW-like animals present gene
      expression alterations in the hippocampus associated with an increased risk of
      cognitive impairment, and to identify early biomarkers of cognitive dysfunction
      in peripheral blood mononuclear cells (PBMC). METHODS: Wistar rats were
      chronically fed with a 60% (HF60) or a 45% (HF45) high-fat diet administered
      isocalorically to control animals to mimic MONW features. Expression analysis of
      cognitive decline-related genes was performed using RT-qPCR, and working memory
      was assessed using a T-maze. RESULTS: High-fat diet consumption altered the
      pattern of gene expression in the hippocampus, clearly pointing to cognitive
      decline, which was accompanied by a worse performance in the T-maze in HF60
      animals. Remarkably, Syn1 and Sorl1 mRNA showed the same expression pattern in
      both the hippocampus and the PBMC obtained at different time-points in the HF60
      group, even before other pathological signs were observed. CONCLUSIONS: Our
      results demonstrate that long-term intake of high-fat diets, even in the absence
      of obesity, leads to cognitive disruption that is reflected in PBMC
      transcriptome. Therefore, PBMC are revealed as a plausible, minimally-invasive
      source of early biomarkers of cognitive impairment associated with increased fat
      intake.

PMID- 29566704
TI  - A case of Cardiobacterium valvarum endocarditis with cerebral hemorrhage after
      MVR, TVP and vegetation removal operation.
AB  - BACKGROUND: Cardiobacterium is a fastidious Gram-negative bacillus, and is a rare
      human pathogen in clinical settings. Herein, we describe a case of
      Cardiobacterium valvarum (C. valvarum) endocarditis with a rare complication of
      cerebral hemorrhage after mitral valve replacement (MVR), tricuspid valve
      prosthesis (TVP) and vegetation removal operation. CASE PRESENTATION: A 41-year
      old woman who had a history of gingivitis developed into infective endocarditis
      due to the infection of C. valvarum. Then, she was hospitalized to receive MVR,
      TVP and vegetation removal operation. The indicators of patient tended to be
      normal until the abrupt cerebral hemorrhage occurred on day 15 after operation.
      This is the first well-described case of C. valvarum infection in China, and the
      first report of C. valvarum endocarditis with cerebral hemorrhage after MVR, TVP
      and vegetation removal operation worldwide. CONCLUSIONS: We reported the first
      case of C. valvarum infection in China clinically, with a rare complication of
      cerebral hemorrhage after MVR, TVP and vegetation removal operation.

PMID- 29566705
TI  - Renal autoregulation and blood pressure management in circulatory shock.
AB  - The importance of personalized blood pressure management is well recognized.
      Because renal pressure-flow relationships may vary among patients, understanding
      how renal autoregulation may influence blood pressure control is essential.
      However, much remains uncertain regarding the determinants of renal
      autoregulation in circulatory shock, including the influence of comorbidities and
      the effects of vasopressor treatment. We review published studies on renal
      autoregulation relevant to the management of acutely ill patients with shock. We
      delineate the main signaling pathways of renal autoregulation, discuss how it can
      be assessed, and describe the renal autoregulatory alterations associated with
      chronic disease and with shock.

PMID- 29566706
TI  - Dexmedetomidine attenuates lung apoptosis induced by renal ischemia-reperfusion
      injury through alpha2AR/PI3K/Akt pathway.
AB  - BACKGROUND: Acute lung injury caused by renal ischemia-reperfusion is one of the
      leading causes of acute kidney injury-related death. Dexmedetomidine, an alpha2
      adrenergic agonist sedative, has been found to have protective effects against
      acute kidney injury and remote lung injury. We sought to determine whether
      dexmedetomidine can exert its anti-apoptotic effects in acute lung injury after
      acute kidney injury, in addition to its common anti-inflammatory effects, and to
      determine the underlying mechanisms. METHODS: In vivo, acute kidney injury was
      induced by 60 min of kidney ischemia (bilateral occlusion of renal pedicles)
      followed by 24 h of reperfusion. Mice received dexmedetomidine (25 ug/kg, i.p.)
      in the absence or presence of alpha2-adrenergic antagonist atipamezole (250
      ug/kg, i.p.) before IR. Histological assessment of the lung was conducted by HE
      staining and arterial blood gases were measured. Lung apoptosis was assessed by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. The
      expression of caspase 3 and p-Akt in lung tissue was detected by western blot. In
      vitro, C57BL/6J mice pulmonary microvascular endothelial cells were treated with
      serum from mice obtained following sham or IR. Dexmedetomidine was given before
      serum stimulation in cells, alone or with atipamezole or LY294002. Cell viability
      was assessed by CCK 8 assay. Cell apoptosis was examined by Hoechst staining and
      Annexin V-FITC/PI staining flow cytometry analysis. Mitochondrial membrane
      potential was measured by flow cytometry. The expression of p-Akt, caspase 3, Bcl
      2 and Bax was measured by western blot. RESULTS: In vivo, dexmedetomidine
      remarkably mitigated pathohistological changes and apoptosis and significantly
      increased p-Akt expression in the lung. In addition, dexmedetomidine also
      slightly improved oxygenation in mice after IR, which can be abolished by
      atipamezole. In vitro, dexmedetomidine significantly inhibited IR serum-induced
      loss of viability and apoptosis in PMVECs. Dexmedetomidine increased p-Akt in a
      time- and dose-dependent manner, and down-regulated the expression of caspase 3
      and Bax and up-regulated the Bcl-2 expression in PMVECs. The changes of MMP were
      also improved by dexmedetomidine. Whilst these effects were abolished by
      Atipamezole or LY294002. CONCLUSION: Our results demonstrated that
      dexmedetomidine attenuates lung apoptosis induced by IR, at least in part, via
      alpha2AR/PI3K/Akt pathway.

PMID- 29566707
TI  - Impact of hypoglycemic episodes on health-related quality of life of type-2
      diabetes mellitus patients: development and validation of a specific QoLHYPO(c)
      questionnaire.
AB  - BACKGROUND: Hypoglycemia is a limiting factor to achieving optimal glycemic
      control in patients with type-2 diabetes mellitus (T2DM), increasing risk of
      death and complications, reducing health-related quality of life (HRQoL) and work
      productivity and increasing healthcare costs. The study's primary objective was
      to develop and validate a specific questionnaire to assess the impact of
      hypoglycemia on the HRQoL of T2DM patients (QoLHYPO(c) questionnaire). METHODS: A
      two-phase multicenter prospective, longitudinal, observational, epidemiologic
      study of consecutively enrolled patients, not involving any drug, was conducted:
      In phase 1 (questionnaire development), patients who had given their written
      informed consent, who were at least 30 years of age, had been diagnosed with T2DM
      at least 5 years prior, had an HbA1c test in the previous 3 months, and a
      hypoglycemic episode in the previous 6 months were included. To validate the
      questionnaire and assess reliability and responsiveness, phase 2 included two
      cohorts of patients. Patients in the reliability cohort would likely have stable
      clinical course during the 3 weeks following inclusion in the study and patients
      in the responsiveness cohort would likely experience changes in their clinical
      course in the 3 months after enrollment. RESULTS: Phase 1 included 168 patients:
      10 attended semi-structured interviews, 18 for face validity, and 140 for the
      pilot test (Rasch analysis). Phase 2 included 227 patients: 142 in the
      reliability cohort and 85 in the responsiveness cohort. Of the 37 items initially
      included in Phase 1, 11 (floor/ceiling effect analysis) and 13 (Rasch analysis)
      were discarded. The final version of the questionnaire consisted of 13 items.
      Phase 2 results showed the questionnaire was unidimensional and able to
      accurately assess HRQoL. Intra-observer reproducibility (ICC = 0.920) and
      internal consistency (Cronbach's alpha: visit 1 = 0.912; visit 2 = 0.901) were
      high, showing high reliability. Internal responsiveness was moderate
      (standardized effect size 0.5-0.8) and external responsiveness was lower (AUC >
      0.5; not statistically significant). Minimal clinically important difference
      (MCID) was estimated to be 3.2 points. CONCLUSIONS: The QoLHYPO(c) questionnaire
      is a tool that can be used in routine clinical practice to assess the impact of
      hypoglycemia on the HRQoL of T2DM patients.

PMID- 29566708
TI  - Seizures in children with neurofibromatosis type 1: is neurofibromatosis type 1
      enough?
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is related to a generally increased
      prevalence of seizures. The mechanism underlying the increased predisposition to
      seizures has not been fully elucidated. The aim of the study was to evaluate the
      role of NF1 in seizures pathogenesis in a cohort of children with NF1 and
      seizures. METHODS: The medical records of 437 children (0-18 years old) with NF1
      were reviewed. All children with at least one afebrile seizure were included.
      Demographic, clinical, neurological, NF1 mutation status, and EEG data were
      collected along with brain magnetic resonance imaging. Depending on etiology,
      structural seizures have been identified and were further classified as NF1
      related or not. RESULTS: Nineteen patients (4.3%; 13 males) were included. NF1
      was inherited in 7 (37.5%), with 3 maternal forms. Ten children with structural
      seizures were identified. Seven forms were identified someway related to NF1, two
      of which were associated to 17q11.2 microdeletion and hypoxic-ischemic
      encephalopathy. Any brain lesion that could explain seizures was found in nine
      patients, two third of these patients had a familiar history of epilepsy.
      CONCLUSIONS: Our results suggest seizures are more frequent in NF1 children
      (4.3%) than in general pediatric population (0.3-0.5%) and that are someway
      related to NF1 in half of patients. Facing seizures in NF1, the clinician should
      first exclude brain tumors but also other, and rarer NF1-related scenarios, such
      as hydrocephalous and vasculopathies. Children with non-structural seizures
      frequently had a family history of epilepsy, raising questions about the
      pathogenic role of NF1. They should be approached as for the general population.

PMID- 29566709
TI  - Cultural significance of the flora of a tropical dry forest in the Doche vereda
      (Villavieja, Huila, Colombia).
AB  - BACKGROUND: In Colombia, ethnobotanical studies regarding plant cultural
      significance (CS) in tropical dry forests are scarce and mainly focused on the
      Caribbean region. Different authors have indicated that the plants with the most
      uses are those of greater cultural importance. Additionally, gender differences
      in knowledge and interest in natural resources has been widely recorded. This
      study evaluated the cultural significance of plants in the Doche community, in
      the Department of Huila. Furthermore, it evaluates the richness of plant
      knowledge among local inhabitants, looking for testing the hypothesis that the CS
      of plants positively correlates to the number of uses people inform about, and
      that there are significant differences on the richness of ethnobotanical
      knowledge between men and women in this community. METHODS: The ethnobotanical
      categories: "food," "condiment," "economy," "fodder," "firewood," "timber",
      "medicine," and "others" were established to carry out semi-structured
      interviews, social cartography, and ethnobotanical walks. The frequency of
      mention was calculated as a measure of CS. The richness of knowledge of each
      collaborator was obtained. Non-parametric tests were performed to determine
      whether differences between the numbers of mentioned species existed between
      genders and ethnobotanical categories. Finally, Pearson correlation tests
      determined the relationship between CS and the number of ethnobotanical
      categories. RESULTS: A hundred useful species were registered in crops and
      forests. The most abundant categories were medicinal (45 species), firewood (30),
      and fodder (28). The most culturally significant species according to frequency
      of mention were Pseudosamanea guachapele, Guazuma ulmifolia, Manihot esculenta,
      and Musa balbisiana. The species with the most registered uses (five) were
      Guazuma ulmifolia and Gliricidia sepium. We found a correlation between CS and
      the number of uses per ethnobotanical category, but no significant difference
      between genders regarding ethnobotanical knowledge. CONCLUSION: Frequency of
      mention provides relevant information about the CS of species. Furthermore, it
      aids to establish sustainable use of tropical dry forests without loss of
      resources parting from strategies designed from within the Doche community and
      based on their ethnobotanical knowledge. We found that the number of uses of a
      plant is correlated with its degree of cultural importance. On the other hand, no
      significant differences were found between genders regarding ethnobotanical
      knowledge; that is, both men and women have similar roles in the community, which
      allows them to recognize the same uses per species.

PMID- 29566710
TI  - Assessment of user voluntary engagement during neurorehabilitation using
      functional near-infrared spectroscopy: a preliminary study.
AB  - BACKGROUND: Functional near infrared spectroscopy (fNIRS) finds extended
      applications in a variety of neuroscience fields. We investigated the potential
      of fNIRS to monitor voluntary engagement of users during neurorehabilitation,
      especially during combinatory exercise (CE) that simultaneously uses both,
      passive and active exercises. Although the CE approach can enhance
      neurorehabilitation outcome, compared to the conventional passive or active
      exercise strategies, the active engagement of patients in active motor movements
      during CE is not known. METHODS: We determined hemodynamic responses induced by
      passive exercise and CE to evaluate the active involvement of users during CEs
      using fNIRS. In this preliminary study, hemodynamic responses of eight healthy
      subjects during three different tasks (passive exercise alone, passive exercise
      with motor imagery, and passive exercise with active motor execution) were
      recorded. On obtaining statistically significant differences, we classified the
      hemodynamic responses induced by passive exercise and CEs to determine the
      identification accuracy of the voluntary engagement of users using fNIRS.
      RESULTS: Stronger and broader activation around the sensorimotor cortex was
      observed during CEs, compared to that during passive exercise. Moreover, pattern
      classification results revealed more than 80% accuracy. CONCLUSIONS: Our
      preliminary study demonstrated that fNIRS can be potentially used to assess the
      engagement of users of the combinatory neurorehabilitation strategy.

PMID- 29566711
TI  - Rising global burden of breast cancer: the case of sub-Saharan Africa (with
      emphasis on Nigeria) and implications for regional development: a review.
AB  - BACKGROUND: Despite mortality from breast cancer in Africa being higher than in
      high income countries, breast cancer has not been extensively studied in the
      region. The aim of this paper was to highlight the rising burden of breast cancer
      with an emphasis on sub-Saharan Africa as well as trends, characteristics,
      controversies and their implications for regional development. METHODOLOGY: A
      review of published studies and documents was conducted in Medline, Scopus,
      Pubmed and Google using combinations of key words-breast neoplasm, breast cancer,
      cancer, incidence, mortality, Africa, Nigeria. Graphical and frequency analyses
      were carried out on some of the incidence and mortality figures retrieved from
      published papers and the GLOBOCAN website. FINDINGS: Globally, about 25% and 15%
      of all new cancer cases and cancer deaths respectively among females were due to
      breast cancer. Africa currently had the highest age-standardized breast cancer
      mortality rate globally, with the highest incidence rates being recorded within
      the sub-Saharan African sub-region. Incidence trends such as inherently
      aggressive tumour and younger age profile had been subject to controversies.
      Certain factors such as westernized diet, urbanization and possibly increasing
      awareness had been implicated, though their specific contributions were yet to be
      fully established. CONCLUSION: Unless urgent action is taken, breast cancer will
      compound sub-Saharan Africa's disease burden, increase poverty and gender
      inequality as well as reverse the current global gains against maternal and
      neonatal mortality.

PMID- 29566712
TI  - The in vitro modulation of steroidogenesis by inflammatory cytokines and insulin
      in TM3 Leydig cells.
AB  - BACKGROUND: Cytokines and hormones, including insulin, are known to modulate the
      hypothalamic-pituitary-testes axis and steroidogenesis, both centrally and
      peripherally. In the context of chronic inflammation and hyperinsulinaemia
      mediating male hypogonadism associated with obesity, metabolic syndrome and type
      2 diabetes mellitus, these mechanisms are poorly understood and the impact of
      cytokines and insulin on Leydig cell steroidogenesis has not been fully elicited.
      This study aimed to further investigate the in vitro impact of TNFalpha, IL1beta,
      IL6, IL8 and insulin on Leydig cell function and steroidogenesis. METHODS: hCG
      stimulated TM3 Leydig cells were exposed to various concentrations of TNFalpha,
      IL1beta, IL6, IL8 (100 ng/ml, 10 ng/ml, 1 ng/ml and 0.1 ng/ml) and insulin (10
      ng/ml, 1 ng/ml, 0.1 ng/ml and 0.01 ng/ml) in optimal cell culture conditions over
      48 h. Cell viability (XTT) and testosterone and progesterone concentrations
      (ELISA) were assessed using standardised laboratory techniques. RESULTS: TNFalpha
      significantly decreased cell viability and progesterone and testosterone
      concentrations in a dose-dependent relationship. IL1beta and IL6 had a subtle but
      significant negative effect on cell viability and testosterone concentrations,
      with a marked significant decrease in progesterone concentration at all
      concentrations investigated. IL8 showed an increase in cell viability, with no
      significant effect on testosterone concentrations alongside a significant
      decrease in progesterone concentrations. Insulin significantly increased cell
      viability and testosterone concentrations in a dose dependent relationship, but
      interestingly significantly decreased progesterone concentrations. CONCLUSIONS:
      The inflammatory cytokines TNFalpha, IL1beta and IL6 cause a dose dependent
      decline in steroidogenesis in TM3 Leydig cells. These results suggest that
      chronic inflammation may downregulate steroidogenesis in males via direct
      modulation of Leydig cell function. However, IL8 may stimulate TM3 Leydig cell
      growth. Insulin is associated with a dose-dependent increase in testosterone
      synthesis, with a significant decline in progesterone synthesis. With the
      phenomenon of insulin resistance, the literature is unclear on the potential role
      of hyperinsulinaemia in steroidogenesis. Further studies are warranted in order
      to fully elicit the molecular mechanisms and interactions of these molecules on
      male steroidogenesis.

PMID- 29566713
TI  - PHD-finger domain protein 5A functions as a novel oncoprotein in lung
      adenocarcinoma.
AB  - BACKGROUND: PHD-finger domain protein 5A (PHF5A) is a highly conserved small
      transcriptional regulator also involved in pre-mRNA splicing; however, its
      biological functions and molecular mechanisms in non-small cell lung cancer
      (NSCLC) have not yet been investigated. The purpose of this study was to
      determine the functional relevance and therapeutic potential of PHF5A in lung
      adenocarcinoma (LAC). METHODS: The expression of PHF5A in LAC tissues and
      adjacent non-tumor (ANT) tissues was investigated using immunohistochemistry of a
      tissue microarray, qRT-PCR, western blot and bioinformatics. The function of
      PHF5A was determined using several in vitro assays and also in vivo assay by
      lentiviral vector-mediated PHF5A depletion in LAC cell lines. RESULTS: PHF5A was
      highly upregulated in LAC tissues compared with the ANT counterparts, and closely
      associated with tumor progression and poor patient prognosis. These results were
      further confirmed by findings of the TCGA database. Moreover, functional studies
      demonstrated that PHF5A knockdown not only resulted in reduced cell
      proliferation, increased cell apoptosis, and cell cycle arrest, but also
      suppressed migration and invasion in LAC cells. PHF5A silencing was also found to
      inhibit LAC tumor growth in nude mice. Microarray and bioinformatics analyses
      revealed that PHF5A depletion led to dysregulation of multiple tumor signaling
      pathways; selected factors in key signaling pathways were verified in vitro.
      CONCLUSIONS: The data suggest for the first time that PHF5A is an oncoprotein
      that contributes to LAC progression by regulating multiple signaling pathways,
      and may constitute a prognostic factor and potential new therapeutic target in
      NSCLC.

PMID- 29566714
TI  - Stability in the feeding practices and styles of low-income mothers:
      questionnaire and observational analyses.
AB  - BACKGROUND: During the last two decades, researchers have devoted considerable
      attention to the role of maternal feeding behaviors, practices, and styles in the
      development of obesity in young children. Little is known, however, about the
      consistency of maternal feeding across settings and time. The purpose of this
      paper was to provide data on this issue by examining the consistency of observed
      maternal feeding behavior across multiple eating occasions, as well as examine
      the consistency of observed and self-reported maternal feeding behavior across 18
      months. METHODS: Videotapes from two studies of low-income mothers and their
      preschool children were coded for feeding practices, dimensions, and styles: a
      study of 137 low-income, African American and Latina mothers and their children
      observed during three meals in their homes over a two to three week period, and a
      study of 138 low-income, Latina mothers observed during a buffet meal in a
      laboratory setting on two separate occasions 18 months apart. Videotapes from
      both studies were coded for a wide range of maternal feeding behaviors and
      strategies. Mothers in the second study also completed three validated, self
      report questionnaires on their feeding practices and styles. RESULTS: Overall,
      both observed and self-reported feeding practices and styles showed only moderate
      levels of stability across meals and over time. Maternal attempts to regulate
      children's eating showed more stability across meals and over time than the
      content of general mealtime conversation. Also, greater stability was found in
      what mothers were trying to get their children to do during the meals than in the
      strategies they used to influence child behavior. Self-reports of feeding showed
      greater stability over time than observational measures. Across meals and across
      18 months, the stability of general feeding styles was between 40% and 50%.
      CONCLUSIONS: The findings demonstrate that maternal feeding behavior was only
      moderately stable across meals and over time-that is, feeding behavior varied
      considerably across situations. The lack of high levels of consistency in feeding
      behavior suggests that situational factors may play a major role in influencing
      maternal behavior as well. Family-focused childhood obesity programs should focus
      not only on helping parents change their feeding practices and styles, but also
      focus on increasing parents' sensitivity to situational factors that affect their
      approach to feeding their children.

PMID- 29566715
TI  - Neoadjuvant intraperitoneal chemotherapy followed by radical surgery and HIPEC in
      patients with very advanced gastric cancer and peritoneal metastases: report of
      an initial experience in a western single center.
AB  - BACKGROUND: The association of preoperative systemic and intraperitoneal
      chemotherapy has been described in Eastern patients with very good outcomes in
      treatment responders. The aim of this paper is to describe the initial results of
      this multidisciplinary regimen in gastric cancer patients with very advanced
      peritoneal metastases. CASE PRESENTATION: We present here the first four cases
      who received the treatment protocol. They had a baseline PCI between 19 and 33.
      Two patients had received systemic chemotherapy prior to this regimen. Three of
      them had significant response and were taken to cytoreductive surgery, while one
      patient who had 12 cycles of chemotherapy previously showed signs of disease
      progression and subsequently died. There was no significant postoperative
      morbidity, and three patients remain alive, two of them with no signs of
      recurrence. CONCLUSION: Systemic and intraperitoneal chemotherapy led to a marked
      response in peritoneal disease extent in our initial experience and allowed three
      of four patients with very advanced disease to be treated with cytoreductive
      surgery.

PMID- 29566716
TI  - Overexpression of zinc-alpha2-glycoprotein suppressed seizures and seizure
      related neuroflammation in pentylenetetrazol-kindled rats.
AB  - BACKGROUND: Zinc-alpha2-glycoprotein (ZAG) is a 42-kDa protein reported as an
      anti-inflammatory adipocytokine. Evidences from clinical and experimental studies
      revealed that brain inflammation plays important roles in epileptogenesis and
      seizure. Interestingly, closely relationship between ZAG and many important
      inflammatory mediators has been proven. Our previous study identified ZAG in
      neurons and found that ZAG is decreased in epilepsy and interacts with TGFbeta
      and ERK. This study aimed to investigate the role of ZAG in seizure and explore
      its effect on seizure-related neuroinflammation. METHODS: We overexpressed AZGP1
      in the hippocampus of rats via adeno-associated virus vector injection and
      observed their seizure behavior and EEG after pentylenetetrazol (PTZ) kindling.
      The level of typical inflammation mediators including TNFalpha, IL-6, TGFbeta,
      ERK, and ERK phosphorylation were determined. RESULTS: The overexpression of
      AZGP1 reduced the seizure severity, prolonged the latency of kindling, and
      alleviated epileptiform discharges in EEG changes induced by PTZ. Overexpression
      of AZGP1 also suppressed the expression of TNFalpha, IL-6, TGFbeta, and ERK
      phosphorylaton in PTZ-kindled rats. CONCLUSIONS: ZAG may inhibit TGFbeta-mediated
      ERK phosphorylation and inhibit neuroinflammation mediated by TNFalpha and IL-6,
      suggesting ZAG may suppress seizure via inhibiting neuroinflammation. ZAG may be
      a potential and novel therapeutic target for epilepsy.

PMID- 29566717
TI  - Toward optimal implementation of cancer prevention and control programs in public
      health: a study protocol on mis-implementation.
AB  - BACKGROUND: Much of the cancer burden in the USA is preventable, through
      application of existing knowledge. State-level funders and public health
      practitioners are in ideal positions to affect programs and policies related to
      cancer control. Mis-implementation refers to ending effective programs and
      policies prematurely or continuing ineffective ones. Greater attention to mis
      implementation should lead to use of effective interventions and more efficient
      expenditure of resources, which in the long term, will lead to more positive
      cancer outcomes. METHODS: This is a three-phase study that takes a comprehensive
      approach, leading to the elucidation of tactics for addressing mis
      implementation. Phase 1: We assess the extent to which mis-implementation is
      occurring among state cancer control programs in public health. This initial
      phase will involve a survey of 800 practitioners representing all states. The
      programs represented will span the full continuum of cancer control, from primary
      prevention to survivorship. Phase 2: Using data from phase 1 to identify
      organizations in which mis-implementation is particularly high or low, the team
      will conduct eight comparative case studies to get a richer understanding of mis
      implementation and to understand contextual differences. These case studies will
      highlight lessons learned about mis-implementation and identify hypothesized
      drivers. Phase 3: Agent-based modeling will be used to identify dynamic
      interactions between individual capacity, organizational capacity, use of
      evidence, funding, and external factors driving mis-implementation. The team will
      then translate and disseminate findings from phases 1 to 3 to practitioners and
      practice-related stakeholders to support the reduction of mis-implementation.
      DISCUSSION: This study is innovative and significant because it will (1) be the
      first to refine and further develop reliable and valid measures of mis
      implementation of public health programs; (2) bring together a strong,
      transdisciplinary team with significant expertise in practice-based research; (3)
      use agent-based modeling to address cancer control implementation; and (4) use a
      participatory, evidence-based, stakeholder-driven approach that will identify key
      leverage points for addressing mis-implementation among state public health
      programs. This research is expected to provide replicable computational
      simulation models that can identify leverage points and public health system
      dynamics to reduce mis-implementation in cancer control and may be of interest to
      other health areas.

PMID- 29566718
TI  - Effect of a live attenuated vaccine against Lawsonia intracellularis in weaned
      and finishing pig settings in Finland.
AB  - BACKGROUND: The intracellular bacterium Lawsonia intracellularis is an important
      pathogen in modern swine production. The aim of this study was to investigate the
      effect of a live attenuated L. intracellularis vaccine (Enterisol Ileitis(r)) on
      the health and production parameters of weaned and finishing pigs in a commercial
      Finnish 850-sow farm with diagnosed L. intracellularis infection. The herd was
      free from enzootic pneumonia, swine dysentery, progressive atrophic rhinitis,
      sarcoptic mange and salmonellosis. Four weekly groups of approximately 500
      piglets were included in the study for a total of approximately 2000 piglets.
      Half of these piglets were vaccinated at 3 weeks of age and the other half served
      as controls. The study piglets were ear-tagged with individual numbers and colour
      coded and were individually weighed at weaning (4 weeks), delivery to the
      finishing farm (12-14 weeks) and at slaughter. Mortality, symptoms of diseases
      and medications of the study piglets were registered in the nursery and finishing
      unit. Feed conversion rate was calculated for the finishing period and lean meat
      percentage was measured at slaughter. RESULTS: Vaccinated piglets had a higher
      live weight than unvaccinated piglets at delivery to the finishing unit (+ 1.18
      kg, P = 0.002) and at slaughter (+ 3.57 kg, P < 0.001). The daily weight gain of
      vaccinated piglets was better than unvaccinated piglets in the nursery (+ 14.8
      g/d, P = 0.013) and in the finishing unit (+ 30.9 g/d, P < 0.001). Vaccination
      had no effect on feed conversion rate or lean meat percentage (P = 0.102).
      Altogether, 3.9 and 4.6% of the pigs were medicated for different reasons in the
      vaccinated and control groups, respectively. The return on investment for the
      vaccination was calculated to be 0.41. CONCLUSIONS: Immunisation of piglets with
      a live attenuated L. intracellularis vaccine resulted in higher meat yield in pig
      production via significantly higher live weight and average daily weight gain in
      a Finnish specific pathogen-free setting.

PMID- 29566719
TI  - Functionalized rare earth-doped nanoparticles for breast cancer nanodiagnostic
      using fluorescence and CT imaging.
AB  - BACKGROUND: Breast cancer is the second leading cause of cancer death among women
      and represents 14% of death in women around the world. The standard diagnosis
      method for breast tumor is mammography, which is often related with false
      negative results leading to therapeutic delays and contributing indirectly to the
      development of metastasis. Therefore, the development of new tools that can
      detect breast cancer is an urgent need to reduce mortality in women. Here, we
      have developed Gd2O3:Eu3+ nanoparticles functionalized with folic acid (FA), for
      breast cancer detection. RESULTS: Gd2O3:Eu3+ nanoparticles were synthesized by
      sucrose assisted combustion synthesis and functionalized with FA using EDC-NHS
      coupling. The FA-conjugated Gd2O3:Eu3+ nanoparticles exhibit strong red emission
      at 613 nm with a quantum yield of ~ 35%. In vitro cytotoxicity studies
      demonstrated that the nanoparticles had a negligible cytotoxic effect on normal
      293T and T-47D breast cancer cells. Cellular uptake analysis showed significantly
      higher internalization of FA-conjugated RE nanoparticles into T-47D cells (Folr
      hi ) compared to MDA-MB-231 breast cancer cells (Folr lo ). In vivo confocal and
      CT imaging studies indicated that FA-conjugated Gd2O3:Eu3+ nanoparticles
      accumulated more efficiently in T-47D tumor xenograft compared to the MDA-MB-231
      tumor. Moreover, we found that FA-conjugated Gd2O3:Eu3+ nanoparticles were well
      tolerated at high doses (300 mg/kg) in CD1 mice after an intravenous injection.
      Thus, FA-conjugated Gd2O3:Eu3+ nanoparticles have great potential to detect
      breast cancer. CONCLUSIONS: Our findings provide significant evidence that could
      permit the future clinical application of FA-conjugated Gd2O3:Eu3+ nanoparticles
      alone or in combination with the current detection methods to increase its
      sensitivity and precision.

PMID- 29566720
TI  - Recalibrating disparities in perceived and actual balance abilities in older
      adults: a mixed-methods evaluation of a novel exergaming intervention.
AB  - BACKGROUND: Published reports suggest a disparity between perceived and actual
      balance abilities, a trait associated with increased fall-risk in older adults.
      We investigate whether it is possible to 'recalibrate' these disparities using a
      novel gaming intervention. METHODS: We recruited 26 older adults for a 4-week
      intervention in which they participated in 8-sessions using a novel gaming
      intervention designed to provide explicit, augmented feedback related to postural
      control. Measures of perceived balance abilities (Falls Efficacy Scale
      International) and actual postural control (limits of stability) were assessed
      pre- and post-intervention. We used focus groups to elicit the opinions of
      participants about how the game may have influenced balance abilities and
      confidence. RESULTS: A stronger alignment was observed between postural control
      and perceived balance capabilities post-intervention (i.e., significant
      correlations between Falls Efficacy Scale-International scores and limits of
      stability which were not present pre-intervention). Also, significant
      improvements in measures of postural control were observed, with these
      improvements confined to the aspects of postural control for which the exergame
      provided explicit, augmented feedback. Qualitative data revealed that the
      intervention made participants more "aware" of their balance abilities.
      CONCLUSIONS: Our results demonstrate that it is possible to recalibrate the
      perceptions of older adults relating to their balance abilities through a
      targeted, short-term intervention. We propose that the post-intervention
      improvements in postural control may have been, in part, the result of this
      recalibration; with altered perceptions leading to changes in balance
      performance. Findings support the application of novel interventions aimed at
      addressing the psychological factors associated with elderly falls.

PMID- 29566721
TI  - Barriers for conducting clinical trials in developing countries- a systematic
      review.
AB  - BACKGROUND: Clinical trials for identification of efficient and effective new
      diagnostic and treatment modalities are needed to address disproportionately high
      burden of communicable (e.g., HIV/AIDS, tuberculosis, and malaria) and non
      communicable diseases (e.g., diabetes) in developing countries. However, gross
      under-representation in global clinical trial platforms contributes to sustained
      health inequity in these countries. We reviewed the literature on barriers facing
      clinical researchers in developing countries for conducting clinical trials in
      their countries. METHODS: Literature indexed in PubMed, Embase, CINAHL and Web of
      Science, WHO Global Health Library were searched. Grey literature was also
      searched. Search key words included barriers, challenges, clinical trials and
      developing countries. Articles within the scope of this review were appraised by
      two reviewers. RESULTS: Ten studies, which are reported in 15 papers, were
      included in this review. Following critical review we identified five unifying
      themes for barriers. Barriers for conducting clinical trials included lack of
      financial and human capacity, ethical and regulatory system obstacles, lack of
      research environment, operational barriers and competing demands. CONCLUSION AND
      RECOMMENDATION: There were substantial barriers at system, organization and
      individual level. We propose that to address this problem, instituting a system
      for wider implementation of local investigator-initiated trials is warranted.
      These trials are more applicable to local populations because they build on local
      healthcare knowledge. They are more demand-led, influence policy and responsive
      to a country's needs because they are driven by a local or national agenda.

PMID- 29566722
TI  - Growth differentiation factor 15 contributes to marrow adipocyte remodeling in
      response to the growth of leukemic cells.
AB  - BACKGROUND: The adipocyte remodeling, including of the morphological change,
      might indicate special pathological function. Our previous study found that the
      morphological remodeling of larger marrow adipocytes into small marrow adipocytes
      correlates with a poor prognosis for acute myeloid leukemia (AML) patients.
      However, the mechanisms contributed to the marrow adipocyte remodeling are still
      poorly understood. METHODS: GDF15 expression was analyzed by RT-qPCR and western
      blotting assays in the leukemic cells. The enhancing and antibody neutralization
      tests in vitro were employed to evaluate the effect of GDF15 on the morphology of
      mature adipocytes. CCK8 test was used to detect the proliferation of leukemic
      cells after co-cultivation with small marrow adipocytes. Flow cytometry was used
      to analysis the proportion of cell cycle of leukemic cells. Immunofluorescence
      staining and linear analysis were applied to verify the GDF15 expression and the
      relationship between GDF15 and small marrow adipocytes in AML patients. RESULTS:
      In this study, we found that leukemic cell lines not only expressed significantly
      higher growth differentiation factor 15 (GDF15) than the other three cytokines
      associated with adipocyte differentiation in RNA level but also secreted GDF15
      factor. Furthermore, the in vitro experiments demonstrated that GDF15 was
      involved in the conversion of small marrow adipocytes from larger marrow
      adipocytes. Correspondingly, the leukemic cells proliferated more rapidly through
      regulating the cell cycle when co-cultured with GDF15-induced small marrow
      adipocytes. The immunofluorescence staining on the bone marrow sections of AML
      patients further exhibited that GDF15 was partly produced by leukemic cells. The
      positive correlation between the concentration of GDF15 in the marrow aspirates
      and the number and the volume of small marrow adipocytes might suggest the
      contribution of GDF15 in AML patients (r = 0.72, r = 0.67). CONCLUSIONS: GDF15
      secreted by leukemic cells was involved in the morphological remodeling of marrow
      adipocytes, which can in turn promote leukemic cell growth, indicating that GDF15
      may be a promising treatment target for AML patients.

PMID- 29566723
TI  - Relationships between work outcomes, work attitudes and work environments of
      health support workers in Ontario long-term care and home and community care
      settings.
AB  - BACKGROUND: Our overarching study objective is to further our understanding of
      the work psychology of Health Support Workers (HSWs) in long-term care and home
      and community care settings in Ontario, Canada. Specifically, we seek novel
      insights about the relationships among aspects of these workers' work
      environments, their work attitudes, and work outcomes in the interests of
      informing the development of human resource programs to enhance elder care.
      METHODS: We conducted a path analysis of data collected via a survey administered
      to a convenience sample of Ontario HSWs engaged in the delivery of elder care
      over July-August 2015. RESULTS: HSWs' work outcomes, including intent to stay,
      organizational citizenship behaviors, and performance, are directly and
      significantly related to their work attitudes, including job satisfaction, work
      engagement, and affective organizational commitment. These in turn are related to
      how HSWs perceive their work environments including their quality of work life
      (QWL), their perceptions of supervisor support, and their perceptions of
      workplace safety. CONCLUSIONS: HSWs' work environments are within the power of
      managers to modify. Our analysis suggests that QWL, perceptions of supervisor
      support, and perceptions of workplace safety present particularly promising means
      by which to influence HSWs' work attitudes and work outcomes. Furthermore, even
      modest changes to some aspects of the work environment stand to precipitate a
      cascade of positive effects on work outcomes through work attitudes.

PMID- 29566724
TI  - Utilization of prevention of mother-to-child transmission (PMTCT) services among
      pregnant women in HIV care in Uganda: a 24-month cohort of women from pre
      conception to post-delivery.
AB  - OBJECTIVE: We assessed the uptake of prevention of mother-to-child transmission
      (PMTCT) services in a cohort of HIV infected women in care at The AIDS Support
      Organization Jinja and Kampala in Uganda, who were trying to conceive, over a
      period of 24 months, to inform the strengthening of PMTCT service access for
      women in care. RESULTS: Of the 299 women 127 (42.5%) reported at least one
      pregnancy within 24 months; 61 women (48.0%) delivered a live child. Of the 55
      who had a live birth at the first pregnancy, 54 (98.2%) used antenatal care (ANC)
      starting at 15.5 weeks of gestation on average and 47/49 (95.9%) delivered at a
      health facility. Excluding miscarriages, 54 (98.2%) received ARVs during
      pregnancy. Of the 49 live births with post-delivery data, 37 (75.5%) tested the
      infant for HIV. 79 of the 127 (68.7%) spoke with providers about childbearing.
      Communication with providers was associated with ANC use (65.8% vs. 41.7%; p =
      .015). Despite the high rate of miscarriages and late ANC start, this study shows
      very high uptake of PMTCT services among PLHIV in care and their infants.
      Improved provider-client communication could enhance ANC attendance and PMTCT
      outcomes among HIV infected women in care.

PMID- 29566725
TI  - Interleukin-37 is increased in adult-onset Still's disease and associated with
      disease activity.
AB  - BACKGROUND: Interleukin (IL)-37 has been known to play an immunosuppressive role
      in various inflammatory disorders, but whether it participates in the regulation
      of pathogenesis of adult-onset Still's disease (AOSD) has not been investigated.
      In this study, we examined serum IL-37 levels and their clinical association with
      AOSD, and we explored the anti-inflammatory effects of IL-37 on peripheral blood
      mononuclear cells (PBMCs) from patients with AOSD. METHODS: Blood samples were
      collected from 62 patients with AOSD and 50 healthy control subjects (HC). The
      serum IL-37 levels were determined using an enzyme-linked immunosorbent assay
      (ELISA). The correlations of serum IL-37 levels with disease activity, laboratory
      values, and inflammatory cytokines in AOSD were analyzed by Spearman's
      correlation test. The correlations between serum IL-37 levels and clinical
      manifestations were analyzed by Mann-Whitney U test. PBMCs from ten patients with
      AOSD were stimulated with recombinant human IL-37 protein, and expression levels
      of tumor necrosis factor (TNF)-alpha, IL-6, IL-10, IL-1beta, and IL-18 were
      determined by qRT-PCR and ELISA. RESULTS: A significantly higher IL-37 protein
      level was observed in patients with AOSD than in HC. Serum IL-37 levels
      correlated with systemic score, laboratory values, IL-1beta, IL-18, and IL-10 in
      patients with AOSD. The expression levels of IL-37 were closely related to the
      patients with AOSD who also had fever, skin rash, lymphadenopathy, splenomegaly,
      myalgia, and arthralgia. Moreover, the production of proinflammatory cytokines
      such as IL-6, IL-1beta, TNF-alpha, and IL-18 in PBMCs from patients with AOSD was
      obviously attenuated after recombinant human IL-37 stimulation. CONCLUSIONS:
      Increased expression of IL-37 and its positive correlation with disease activity
      suggest its involvement in AOSD pathogenesis. More importantly, IL-37 inhibits
      the expression of proinflammatory cytokines in PBMCs from patients with AOSD,
      indicating the potential anti-inflammatory role of IL-37 in AOSD. Thus, IL-37 may
      be a novel disease activity biomarker and research target in AOSD.

PMID- 29566727
TI  - Myocellular characteristics in rheumatoid arthritis and osteoarthritis patients.

PMID- 29566726
TI  - Increased circulating resistin levels in early-onset breast cancer patients of
      normal body mass index correlate with lymph node negative involvement and longer
      disease free survival: a multi-center POSH cohort serum proteomics study.
AB  - BACKGROUND: Early-onset breast cancer (EOBC) affects about one in 300 women aged
      40 years or younger and is associated with worse outcomes than later onset breast
      cancer. This study explored novel serum proteins as surrogate markers of
      prognosis in patients with EOBC. METHODS: Serum samples from EOBC patients
      (stages 1-3) were analysed using agnostic high-precision quantitative proteomics.
      Patients received anthracycline-based chemotherapy. The discovery cohort (n =
      399) either had more than 5-year disease-free survival (DFS) (good outcome group,
      n = 203) or DFS of less than 2 years (poor outcome group, n = 196). Expressed
      proteins were assessed for differential expression between the two groups.
      Bioinformatics pathway and network analysis in combination with literature
      research were used to determine clinically relevant proteins. ELISA analysis
      against an independent sample set from the Prospective study of Outcomes in
      Sporadic versus Hereditary breast cancer (POSH) cohort (n = 181) was used to
      validate expression levels of the selected target. Linear and generalized linear
      modelling was applied to determine the effect of target markers, body mass index
      (BMI), lymph node involvement (LN), oestrogen receptor (ER), progesterone
      receptor and human epidermal growth factor receptor 2 status on patients'
      outcome. RESULTS: A total of 5346 unique proteins were analysed (peptide FDR p <=
      0.05). Of these, 812 were differentially expressed in the good vs poor outcome
      groups and showed significant enrichment for the insulin signalling (p = 0.01)
      and the glycolysis/gluconeogenesis (p = 0.01) pathways. These proteins further
      correlated with interaction networks involving glucose and fatty acid metabolism.
      A consistent nodal protein to these metabolic networks was resistin (upregulated
      in the good outcome group, p = 0.009). ELISA validation demonstrated resistin to
      be upregulated in the good outcome group (p = 0.04), irrespective of BMI and ER
      status. LN involvement was the only covariate with a significant association with
      resistin measurements (p = 0.004). An ancillary in-silico observation was the
      induction of the inflammatory response, leucocyte infiltration, lymphocyte
      migration and recruitment of phagocytes (p < 0.0001, z-score > 2). Survival
      analysis showed that resistin overexpression was associated with improved DFS.
      CONCLUSIONS: Higher circulating resistin correlated with node-negative patients
      and longer DFS independent of BMI and ER status in women with EOBC.
      Overexpression of serum resistin in EOBC may be a surrogate indicator of improved
      prognosis.

PMID- 29566729
TI  - Intrauterine resuscitation during the second stage of term labour by maternal
      hyperoxygenation versus conventional care: study protocol for a randomised
      controlled trial (INTEREST O2).
AB  - BACKGROUND: Perinatal asphyxia is, even in developed countries, one the major
      causes of neonatal morbidity and mortality. Therefore, if foetal distress during
      labour is suspected, one should try to restore foetal oxygen levels or aim for
      immediate delivery. However, studies on the effect of intrauterine resuscitation
      during labour are scarce. We designed a randomised controlled trial to
      investigate the effect of maternal hyperoxygenation on the foetal condition. In
      this study, maternal hyperoxygenation is induced for the treatment of foetal
      distress during the second stage of term labour. METHODS/DESIGN: This study is a
      single-centre randomised controlled trial being performed in a tertiary hospital
      in The Netherlands. From among cases of a suboptimal or abnormal foetal heart
      rate pattern during the second stage of term labour, a total of 116 patients will
      be randomised to the control group, where normal care is provided, or to the
      intervention group, where before normal care 100% oxygen is supplied to the
      mother by a non-rebreathing mask until delivery. The primary outcome is change in
      foetal heart rate pattern. Secondary outcomes are Apgar score, mode of delivery,
      admission to the neonatal intensive care unit and maternal side effects. In
      addition, blood gas values and malondialdehyde are determined in umbilical cord
      blood. DISCUSSION: This study will be the first randomised controlled trial to
      investigate the effect of maternal hyperoxygenation for foetal distress during
      labour. This intervention should be recommended only as a treatment for
      intrapartum foetal distress, when improvement of the foetal condition is likely
      and outweighs maternal and neonatal side effects. TRIAL REGISTRATION: EudraCT,
      2015-001654-15; registered on 3 April 2015. Dutch Trial Register, NTR5461;
      registered on 20 October 2015.

PMID- 29566728
TI  - The association of mammographic density with risk of contralateral breast cancer
      and change in density with treatment in the WECARE study.
AB  - BACKGROUND: Mammographic density (MD) is an established predictor of risk of a
      first breast cancer, but the relationship of MD to contralateral breast cancer
      (CBC) risk is not clear, including the roles of age, mammogram timing, and change
      with treatment. Multivariable prediction models for CBC risk are needed and MD
      could contribute to these. METHODS: We conducted a case-control study of MD and
      CBC risk in phase II of the WECARE study where cases had a CBC diagnosed >= 2
      years after first diagnosis at age <55 years and controls had unilateral breast
      cancer (UBC) with similar follow-up time. We retrieved film mammograms of the
      unaffected breast from two time points, prior to/at the time of the first
      diagnosis (253 CBC cases, 269 UBC controls) and >= 6 months up to 48 months
      following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were
      digitized and percent MD (%MD) was measured using the thresholding program
      Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association
      between %MD and CBC, adjusted for age, treatment, and other factors related to
      CBC, were estimated using logistic regression. Linear regression was used to
      estimate the association between treatment modality and change in %MD in 467
      women with mammograms at both time points. RESULTS: For %MD assessed following
      diagnosis, there was a statistically significant trend of increasing CBC with
      increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk
      of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but
      weaker, associations were noted for %MD measurements prior to/at diagnosis. The
      relationship appeared strongest in women aged < 45 years and non-existent in
      women aged 50 to 54 years. A decrease of >= 10% in %MD between first and second
      mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI
      0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were
      associated with statistically significant 3% decreases in %MD (p < 0.01).
      CONCLUSIONS: Post-diagnosis measures of %MD may be useful to include in CBC risk
      prediction models with consideration of age at diagnosis. Chemotherapy is
      associated with reductions in %MD, similar to tamoxifen.

PMID- 29566731
TI  - Deep vein thrombosis and pulmonary embolism secondary to urinary retention: a
      case report.
AB  - BACKGROUND: Pulmonary embolism occurs when a blood thrombus forms and travels
      from a vein in the body to an artery in the lung. Thrombi often develop in one of
      the deep veins of the legs, thighs, or pelvis, a condition known as deep vein
      thrombosis. In this report, we describe a rare instance of a patient who
      developed deep vein thrombosis and pulmonary embolism secondary to urinary
      retention, and we also review some of the literature. CASE PRESENTATION: A 75
      year-old Japanese man visited our hospital with the complaint of lower extremity
      weakness. A physical examination revealed bilateral leg edema. Contrast-enhanced
      computed tomography showed thrombi in both the bilateral intrapelvic veins and
      the right pulmonary artery, with an extremely distended bladder. We diagnosed
      deep vein thrombosis and pulmonary embolism due to urinary retention, which was
      attributed to detrusor insufficiency owing to both taking an anticholinergic drug
      and neurogenic bladder. The patient was immediately started on both management of
      voiding dysfunction and anticoagulant therapy. CONCLUSIONS: We encountered a
      patient with deep vein thrombosis and pulmonary embolism secondary to urinary
      retention that could have been fatal. In such cases, clinicians should always
      take into account appropriate management of voiding dysfunction.

PMID- 29566730
TI  - Collaborative care for the detection and management of depression among adults
      with hypertension in South Africa: study protocol for the PRIME-SA randomised
      controlled trial.
AB  - BACKGROUND: The high co-morbidity of mental disorders, particularly depression,
      with non-communicable diseases (NCDs) such as cardiovascular disease (CVD), is
      concerning given the rising burden of NCDs globally, and the role depression
      plays in confounding prevention and treatment of NCDs. The objective of this
      randomised control trial (RCT) is to determine the real-world effectiveness of
      strengthened depression identification and management on depression outcomes in
      hypertensive patients attending primary health care (PHC) facilities in South
      Africa (SA). METHODS/DESIGN: The study design is a pragmatic, two-arm, parallel
      cluster RCT, the unit of randomisation being the clinics, with outcomes being
      measured for individual participants. The 20 largest eligible clinics from one
      district in the North West Province are enrolled in the trial. Equal numbers of
      hypertensive patients (n = 50) identified as having depression using the Patient
      Health Questionnaire (PHQ-9) are enrolled from each clinic, making up a total of
      1000 participants with 500 in each arm. The nurse clinicians in the control
      facilities receive the standard training in Primary Care 101 (PC101), a clinical
      decision support tool for integrated chronic care that includes guidelines for
      hypertension and depression care. Referral pathways available include referrals
      to PHC physicians, clinical or counselling psychologists and outpatient
      psychiatric and psychological services. In the intervention clinics, this
      training is supplemented with strengthened training in the depression components
      of PC101 as well as training in clinical communication skills for nurse-led
      chronic care. Referral pathways are strengthened through the introduction of a
      facility-based behavioural health counsellor, trained to provide structured
      manualised counselling for depression and adherence counselling for all chronic
      conditions. The primary outcome is defined as at least 50% reduction in PHQ-9
      score measured at 6 months. DISCUSSION: This trial should provide evidence of the
      real world effectiveness of strengtheneddepression identification and
      collaborative management on health outcomes of hypertensive patients withcomorbid
      depression attending PHC facilities in South Africa. TRIAL REGISTRATION: South
      African National Clinical Trial Register: SANCTR (
      http://www.sanctr.gov.za/SAClinicalTrials ) (DOH-27-0916-5051). Registered on 9
      April 2015. ClinicalTrials.gov : ID: NCT02425124 . Registered on 22 April 2015.

PMID- 29566732
TI  - Multiple-level stakeholder engagement in malaria clinical trials: addressing the
      challenges of conducting clinical research in resource-limited settings.
AB  - BACKGROUND: Multinational clinical trials are logistically complex and require
      close coordination between various stakeholders. They must comply with global
      clinical standards and are accountable to multiple regulatory and ethical bodies.
      In resource-limited settings, it is challenging to understand how to apply global
      clinical standards to international, national, and local factors in clinical
      trials, making multiple-level stakeholder engagement an important element in the
      successful conduct of these clinical trials. MAIN BODY: During the planning and
      implementation of a large multinational clinical trial for intermittent
      preventive treatment of malaria in pregnancy in resource-limited areas of sub
      Saharan Africa, we encountered numerous challenges, which required implementation
      of a range of engagement measures to ensure compliance with global clinical and
      regulatory standards. These challenges included coordination with ongoing global
      malaria efforts, heterogeneity in national regulatory structures, sub-optimal
      healthcare infrastructure, local practices and beliefs, and perspectives that
      view healthcare providers with undue trust or suspicion. In addition to
      engagement with international bodies, such as the World Health Organization, the
      Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the
      London School of Hygiene and Tropical Medicine, in order to address the
      challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the
      "Sponsoring Entities" for these studies) and investigators liaised with national-
      and district-level stakeholders such as health ministers and regional/local
      community health workers. Community engagement measures undertaken by
      investigators included local meetings with community leaders to explain the
      research aims and answer questions and concerns voiced by the community. The
      investigators also engaged with family members of prospective trial participants
      in order to be sensitive to local practices and beliefs. CONCLUSION: Engagement
      with key stakeholders at international and national levels enabled the Sponsoring
      Entities to address challenges by aligning the study design with the requirements
      of health and regulatory agencies and to understand and address healthcare
      infrastructure needs prior to trial initiation. Local stakeholder engagement,
      including community members, study participants, and family enabled the
      investigators to address challenges by ensuring that study design and conduct
      were adapted to local considerations and ensuring accurate information about the
      study aims was shared with the public. TRIAL REGISTRATION: ClinicalTrials.gov,
      ID: NCT01103063 . Registered on 7 April 2010.

PMID- 29566733
TI  - Comparison and optimization of CRISPR/dCas9/gRNA genome-labeling systems for live
      cell imaging.
AB  - CRISPR/dCas9 binds precisely to defined genomic sequences through targeting of
      guide RNA (gRNA) sequences. In vivo imaging of genomic loci can be achieved by
      recruiting fluorescent proteins using either dCas9 or gRNA. We thoroughly
      validate and compare the effectiveness and specificity of several dCas9/gRNA
      genome labeling systems. Surprisingly, we discover that in the gRNA-labeling
      strategies, accumulation of tagged gRNA transcripts leads to non-specific
      labeling foci. Furthermore, we develop novel bimolecular fluorescence
      complementation (BIFC) methods that combine the advantages of both dCas9-labeling
      and gRNA-labeling strategies. The BIFC-dCas9/gRNA methods demonstrate high signal
      to-noise ratios and have no non-specific foci.

PMID- 29566735
TI  - Feasibility and reliability of the Spondyloarthritis Research Consortium of
      Canada sacroiliac joint inflammation score in children.
AB  - BACKGROUND: Published methods for quantification of magnetic resonance imaging
      (MRI) evidence of inflammation in the sacroiliac joint lack validation in
      pediatric populations. We evaluated the reliability and construct validity of the
      Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint
      inflammation score (SIS) in children with suspected or confirmed juvenile
      spondyloarthritis (JSpA). METHODS: The SPARCC SIS measures the presence, depth,
      and intensity of bone marrow inflammation on MRI through the cartilaginous part
      of the joint. Six readers blinded to clinical details except age, participated in
      two reading exercises, each preceded by a calibration exercise. Inter-observer
      reliability was assessed using intraclass correlation coefficients (ICCs) and for
      pre-specified acceptable reliability the inraclass correlation coefficient (ICC)
      was > 0.8. RESULTS: The SPARCC SIS had face validity and was feasible to score in
      pediatric cases in both reading exercises. Cases were mostly male (64%) and the
      median age at the time of imaging was 14.9 years. After calibration, the median
      ICC across all readers for the SIS total score was 0.81 (IQR 0.71-0.89). SPARCC
      SIS had weak correlation with disease activity (DA) as measured by the JSpADA (r
      = - 0.12) but discriminated significantly between those with and without elevated
      C-reactive protein (p = 0.03). CONCLUSION: The SPARCC SIS was feasible to score
      and had acceptable reliability in children. The ICC improved with additional
      calibration and reading exercises, for both experienced and inexperienced
      readers.

PMID- 29566734
TI  - Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute
      respiratory distress syndrome?
AB  - Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by
      progressive loss of lung function and poor prognosis. The so-called acute
      exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical
      ventilation in the intensive care unit (ICU). AE-IPF shares several
      pathophysiological features with acute respiratory distress syndrome (ARDS), a
      very severe condition commonly treated in this setting.A review of the literature
      has been conducted to underline similarities and differences in the management of
      patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive
      loss of aeration occurs, similar to what is observed in patients with ARDS.
      Differently from ARDS, no studies have yet concluded on the optimal ventilatory
      strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding,
      a protective ventilation strategy with low tidal volume and low driving pressure
      could be recommended similarly to ARDS. The beneficial effect of high levels of
      positive end-expiratory pressure and prone positioning has still to be elucidated
      in AE-IPF patients, as well as the precise role of other types of respiratory
      assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies
      (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as
      steroids or immunosuppressive agents in AE-IPF is controversial and potentially
      associated with an increased risk of serious adverse reactions.Common
      pathophysiological abnormalities and similar clinical needs suggest translating
      to AE-IPF the lessons learned from the management of ARDS patients. Studies
      focused on specific therapeutic strategies during AE-IPF are warranted.

PMID- 29566736
TI  - Impact of diuretics on the urate lowering therapy in patients with gout: analysis
      of an inception cohort.
AB  - BACKGROUND: Diuretics have been associated with impaired response and
      refractoriness in gout, but whether this effect is still present with new urate
      lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the
      present study was to assess the impact of the diuretics on the response to ULD in
      patients with gout.  METHODS: This was a retrospective analysis of an inception
      cohort. Participants were classified according to the type of ULD prescribed. We
      analysed the maximal dose of ULD (primary outcome variable), serum urate (SU)
      reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4
      mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or
      thiazide). We adjusted for confounders using multiple linear regression analysis.
      RESULTS: We included 245 patients: 208 treated with allopurinol (66 on diuretics,
      31.7%), 35 with febuxostat (19 on diuretics, 57.6%), and 2 with benzbromarone.
      Significantly fewer participants in the allopurinol plus diuretics subgroup
      achieved SU levels of less than 5 mg/dL, but we found no other significant
      differences in SU targets associated with diuretics. Regarding the maximum ULD
      dose, a simple linear regression suggested an inverse relationship with diuretics
      (beta = - 0.125, p = 0.073), but this did not hold in the multivariable analysis
      (beta = - 0.47, p = 0.833). There was no association with febuxostat (beta = -
      0.116, p = 0.514). CONCLUSION: Diuretics do not appear to have a significant
      impact on managing gout.

PMID- 29566737
TI  - Murine breast cancer feed arteries are thin-walled with reduced alpha1A
      adrenoceptor expression and attenuated sympathetic vasocontraction.
AB  - BACKGROUND: Perfusion of breast cancer tissue limits oxygen availability and
      metabolism but angiogenesis inhibitors have hitherto been unsuccessful for breast
      cancer therapy. In order to identify abnormalities and possible therapeutic
      targets in mature cancer arteries, we here characterize the structure and
      function of cancer feed arteries and corresponding control arteries from female
      FVB/N mice with ErbB2-induced breast cancer. METHODS: We investigated the
      contractile function of breast cancer feed arteries and matched control arteries
      by isometric myography and evaluated membrane potentials and intracellular [Ca2+]
      using sharp electrodes and fluorescence microscopy, respectively. Arterial wall
      structure is assessed by transmission light microscopy of arteries mounted in
      wire myographs and by evaluation of histological sections using the unbiased
      stereological disector technique. We determined the expression of messenger RNA
      by reverse transcription and quantitative polymerase chain reaction and studied
      receptor expression by confocal microscopy of arteries labelled with the BODIPY
      tagged alpha1-adrenoceptor antagonist prazosin. RESULTS: Breast cancer feed
      arteries are thin-walled and produce lower tension than control arteries of
      similar diameter in response to norepinephrine, thromboxane-analog U46619,
      endothelin-1, and depolarization with elevated [K+]. Fewer layers of similarly
      sized vascular smooth muscle cells explain the reduced media thickness of breast
      cancer arteries. Evidenced by lower media stress, norepinephrine-induced and
      thromboxane-induced tension development of breast cancer arteries is reduced more
      than is explained by the thinner media. Conversely, media stress during
      stimulation with endothelin-1 and elevated [K+] is similar between breast cancer
      and control arteries. Correspondingly, vascular smooth muscle cell
      depolarizations and intracellular Ca2+ responses are attenuated in breast cancer
      feed arteries during norepinephrine but not during endothelin-1 stimulation.
      Protein expression of alpha1-adrenoceptors and messenger RNA levels for alpha1A
      adrenoceptors are lower in breast cancer arteries than control arteries.
      Sympathetic vasocontraction elicited by electrical field stimulation is inhibited
      by alpha1-adrenoceptor blockade and reduced in breast cancer feed arteries
      compared to control arteries. CONCLUSION: Thinner media and lower alpha1
      adrenoceptor expression weaken contractions of breast cancer feed arteries in
      response to sympathetic activity. We propose that abnormalities in breast cancer
      arteries can be exploited to modify tumor perfusion and thereby either starve
      cancer cells or facilitate drug and oxygen delivery during chemotherapy or
      radiotherapy.

PMID- 29566738
TI  - Fecal microbiota transplantation against intestinal colonization by extended
      spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.
AB  - OBJECTIVE: Infections with multidrug-resistant microorganisms are associated with
      increased hospitalization, medication costs and mortality. Based on our fecal
      microbiota transplantation (FMT) experience for Clostridium difficile infection,
      we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with
      FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained,
      amounting to a total number of 22 transplants. The objective was decolonization
      of ESBL-EB. RESULTS: Three out of fifteen (20%) patients were ESBL-negative at 1,
      2 and 4 weeks after the first transplant, while six out of 15 (40%) were negative
      after the second transplant. Comparison of fecal microbiota at baseline and 4
      weeks after FMT revealed restoration of microbial diversity after FMT and a
      microbial shift towards donor composition. Finally, we suggest several possible
      factors of response to therapy, such as donor-recipient microbiota match and
      number of FMTs. Therefore, FMT can be an effective treatment in patients carrying
      ESBL-EB. Response may be determined by microbiota composition and number of FMT
      procedures. Trial registration ISRCTN ISRCTN48328635 Registered 11 October 2017,
      retrospectively registered.

PMID- 29566740
TI  - Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate
      in patients with rheumatoid arthritis: patient-reported outcomes.
AB  - BACKGROUND: The aim was to assess patient-reported outcomes (PROs) in patients
      with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24
      week, randomized, placebo-controlled studies. METHODS: Patients with moderate-to
      severe active RA and an inadequate response to methotrexate (MTX) were randomized
      to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX
      (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders
      receiving filgotinib 50 mg in both studies or placebo in the add-on study, and
      all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100
      mg. PROs were measured using the Health Assessment Questionnaire - Disability
      Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the
      Patient Global Assessment of Disease Activity (Patient Global), the Functional
      Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the
      36-Item Short Form Health Survey (SF-36). RESULTS: At week 12, improvements in
      all PROs, apart from the SF-36 mental component in the add-on study, were
      statistically better with filgotinib than placebo; some improvements were noted
      as early as the first assessment time point (week 1 or week 4). Filgotinib
      improved HAQ-DI by 0.58-0.84 points, FACIT-Fatigue by 6.9-11.4 points, Patient
      Global by 25.2-35.6 mm, and Pain by 24.2-37.9 mm; scores were maintained or
      improved to week 24. Across all PROs, more patients achieved minimal clinically
      important differences and normative values with filgotinib 200 mg than placebo.
      Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in
      PROs between weeks 12 to 24. CONCLUSIONS: Filgotinib as MTX add-on therapy or as
      monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health
      related quality of life and functional status in patients with active RA. TRIAL
      REGISTRATION: MTX add-on study: ClinicalTrials.gov , NCT01888874 . Registered on
      28 June 2013. Monotherapy study: ClinicalTrials.gov , NCT01894516 . Registered on
      10 July 2013.

PMID- 29566739
TI  - Collaborative care for the detection and management of depression among adults
      receiving antiretroviral therapy in South Africa: study protocol for the CobALT
      randomised controlled trial.
AB  - BACKGROUND: The scale-up of antiretroviral treatment (ART) programmes has seen
      HIV/AIDS transition to a chronic condition characterised by high rates of
      comorbidity with tuberculosis, non-communicable diseases (NCDs) and mental health
      disorders. Depression is one such disorder that is associated with higher rates
      of non-adherence, progression to AIDS and greater mortality. Detection and
      treatment of comorbid depression is critical to achieve viral load suppression in
      more than 90% of those on ART and is in line with the recent 90-90-90 Joint
      United Nations Programme on HIV/AIDS (UNAIDS) targets. The CobALT trial aims to
      provide evidence on the effectiveness and cost-effectiveness of scalable
      interventions to reduce the treatment gap posed by the growing burden of
      depression among adults on lifelong ART. METHODS: The study design is a
      pragmatic, parallel group, stratified, cluster randomised trial in 40 clinics
      across two rural districts of the North West Province of South Africa. The unit
      of randomisation is the clinic, with outcomes measured among 2000 patients on ART
      who screen positive for depression using the Patient Health Questionnaire (PHQ
      9). Control group clinics are implementing the South African Department of
      Health's Integrated Clinical Services Management model, which aims to reduce
      fragmentation of care in the context of rising multimorbidity, and which includes
      training in the Primary Care 101 (PC101) guide covering communicable diseases,
      NCDs, women's health and mental disorders. In intervention clinics, we
      supplemented this with training specifically in the mental health components of
      PC101 and clinical communications skills training to support nurse-led chronic
      care. We strengthened the referral pathways through the introduction of a clinic
      based behavioural health counsellor equipped to provide manualised depression
      counselling (eight sessions, individual or group), as well as adherence
      counselling sessions (one session, individual). The co-primary patient outcomes
      are a reduction in PHQ-9 scores of at least 50% from baseline and viral load
      suppression rates measured at 6 and 12 months, respectively. DISCUSSION: The
      trial will provide real-world effectiveness of case detection and collaborative
      care for depression including facility-based counselling on the mental and
      physical outcomes for people on lifelong ART in resource-constrained settings.
      TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02407691 ) registered on 19 March
      2015; Pan African Clinical Trials Registry ( 201504001078347 ) registered on
      19/03/2015; South African National Clinical Trials Register (SANCTR) ( DOH-27
      0515-5048 ) NHREC number 4048 issued on 21/04/2015.

PMID- 29566741
TI  - The amino acid transporter SLC7A5 confers a poor prognosis in the highly
      proliferative breast cancer subtypes and is a key therapeutic target in luminal B
      tumours.
AB  - BACKGROUND: Breast cancer (BC) is a heterogeneous disease characterised by
      variant biology and patient outcome. The amino acid transporter, SLC7A5, plays a
      role in BC although its impact on patient outcome in different BC subtypes
      remains to be validated. This study aimed to determine whether the
      clinicopathological and prognostic value of SLC7A5 is different within the
      molecular classes of BC. METHODS: SLC7A5 was assessed at the genomic level, using
      Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data (n =
      1980), and proteomic level, using immunohistochemical analysis and tissue
      microarray (TMA) (n = 2664; 1110 training and 1554 validation sets) in well
      characterised primary BC cohorts. SLC7A5 expression correlated with
      clinicopathological and biological parameters, molecular subtypes and patient
      outcome. RESULTS: SLC7A5 mRNA and protein expression were strongly correlated
      with larger tumour size and higher grade. High expression was observed in triple
      negative (TN), human epidermal growth factor receptor 2 (HER2)+, and luminal B
      subtypes. SLC7A5 mRNA and protein expression was significantly associated with
      the expression of the key regulator of tumour cell metabolism, c-MYC,
      specifically in luminal B tumours only (p = 0.001). High expression of SLC7A5
      mRNA and protein was associated with poor patient outcome (p < 0.001) but only in
      the highly proliferative oestrogen receptor (ER)+/ luminal B (p = 0.007) and
      HER2+ classes of BC (p = 0.03). In multivariate analysis, SLC7A5 protein was an
      independent risk factor for shorter breast-cancer-specific survival only in ER+
      high-proliferation tumours (p = 0.02). CONCLUSIONS: SLC7A5 appears to play a role
      in the aggressive highly proliferative ER+ subtype driven by MYC and could act as
      a potential therapeutic target. Functional assessment is necessary to reveal the
      specific role played by this transporter in the ER+ highly proliferative subclass
      and HER2+ subclass of BC.

PMID- 29566742
TI  - Smoking is not linked to the development of anti-peptidylarginine deiminase 4
      autoantibodies in rheumatoid arthritis.
AB  - BACKGROUND: Defining environmental factors responsible for development of
      autoimmunity in rheumatoid arthritis (RA) is critical for understanding
      mechanisms of disease initiation and propagation. Notably, a history of cigarette
      smoking has been implicated in the genesis of RA and is associated with worse
      disease outcomes. Antibodies to peptidylarginine deiminase 4 (PAD4) are also
      associated with more severe RA. A subset of patients who have PAD4 autoantibodies
      that cross-react with PAD3 (anti-PAD3/4) are at the highest risk for interstitial
      lung disease, and this risk is augmented by a history of cigarette smoking. It is
      unclear, however, if smoking is etiologically linked to the development of anti
      PAD4 antibodies. METHODS: Patients were included in this study if they had
      physician-diagnosed RA as well as DNA, serum, and a date-matched clinical
      assessment (n = 274). Anti-PAD4 and anti-CCP antibodies were measured by
      immunoprecipitation and ELISA, respectively; shared epitope (SE) status was
      determined by HLA-DRbeta1 genotyping. Logistic regression analysis was used to
      evaluate associations of smoking with PAD4 antibodies, with adjustment for
      relevant demographic and clinical features. Stratified analyses by disease
      duration and shared epitope status were also performed. RESULTS: Anti-PAD4
      antibodies were present in 25% of RA patients, with 50% of these individuals
      having anti-PAD3/4 cross-reactive antibodies. Anti-PAD4 antibodies were
      significantly associated with a longer disease duration, SE alleles, and anti-CCP
      antibodies. Importantly, there were no significant differences in smoking history
      between anti-PAD4 positive and negative groups in univariate analyses, stratified
      analyses, or multivariable models. However, an inverse relationship between
      smoking and anti-PAD4 antibodies was suggested by a lower prevalence of current
      smokers among patients with anti-PAD3/4 antibodies compared to antibody negative
      individuals (p = 0.04). Further, the lowest levels of anti-PAD4 antibodies were
      observed in current smokers (p = 0.14), and a significant association of SE and
      anti-PAD4 antibodies was only present among never smokers (p = 0.01).
      CONCLUSIONS: Smoking history was not associated with anti-PAD4 antibodies in
      patients with RA. The finding that anti-PAD4 antibodies were not associated with
      smoking suggests that other environmental factors may contribute to the
      development of autoimmunity to PAD4 in these patients.

PMID- 29566743
TI  - Electronic cigarettes use and perception amongst medical students: a cross
      sectional survey from Sindh, Pakistan.
AB  - OBJECTIVE: The manufacturers of electronic cigarettes (e-cigarettes) are actively
      marketing their product through electronic and social media. Undergraduate
      medical students are expected to have better knowledge and awareness as they
      directly interact with patients in their training, The purpose of this study is
      therefore, to determine knowledge, use and perception regarding e-cigarettes
      among medical students from Sindh, Pakistan. RESULTS: A cross-sectional study was
      conducted between 1st July and 30th September 2016 at five different medical
      colleges situated in the second largest province of Sindh, Pakistan. The data was
      collected through a structured, self-administered questionnaire. Of the 500
      students, the mean age was 21.5 +/- 1.7 years and 58% were females. Over (65.6%)
      students were aware of e-cigarettes, 31 (6.2%) reported having used e-cigarettes,
      of whom 6 (1.2%) self-reported daily use. Users of conventional tobacco products
      were significantly more likely to have heard of e-cigarettes (87.6% vs 51.6%, p <
      0.001) and having used them (13.9% vs 1.3%, p < 0.001). On multivariable logistic
      regression analysis we found a strong association of e-cigarette use with
      consumption of conventional cigarettes [OR: 10.6, 95% CI 3.6-30.8, p < 0.001],
      use of smokeless tobacco products [OR: 7.9, 95% CI 2.7-23.4, p < 0.001] however a
      weak association was observed for Shisha use [OR: 3.05, 95% CI 0.9-9.6, p =
      0.05].

PMID- 29566744
TI  - Exercise combined with Acceptance and Commitment Therapy (ExACT) compared to a
      supervised exercise programme for adults with chronic pain: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Acceptance and Commitment Therapy (ACT) is a form of cognitive
      behavioural therapy, which may be beneficial for people with chronic pain. The
      approach aims to enhance daily functioning through increased psychological
      flexibility. Whilst the therapeutic model behind ACT appears well suited to
      chronic pain, there is a need for further research to test its effectiveness in
      clinical practice, particularly with regards to combining ACT with physical
      exercise. METHODS/DESIGN: This prospective, two-armed, parallel-group, single
      centre randomised controlled trial (RCT) will assess the effectiveness of a
      combined Exercise and ACT programme, in comparison to supervised exercise for
      chronic pain. One hundred and sixty patients, aged 18 years and over, who have
      been diagnosed with a chronic pain condition by a physician will be recruited to
      the trial. Participants will be individually randomised to one of two 8-week,
      group interventions. The combined group will take part in weekly psychology
      sessions based on the ACT approach, in addition to supervised exercise classes
      led by a physiotherapist. The control group will attend weekly supervised
      exercise classes but will not take part in an ACT programme. The primary outcome
      will be pain interference at 12-week follow-up, measured using the Brief Pain
      Inventory-Interference Scale. Secondary outcomes will include self-reported pain
      severity, self-perception of change, patient satisfaction, quality of life,
      depression, anxiety and healthcare utilisation. Treatment process measures will
      include self-efficacy, pain catastrophising, fear avoidance, pain acceptance and
      committed action. Physical activity will be measured using Fitbit ZipTM activity
      trackers. Both groups will be followed up post intervention and again after 12
      weeks. Estimates of treatment effects at follow-up will be based on an intention
      to-treat framework, implemented using a linear mixed-effects model. Individual
      and focus group qualitative interviews will be undertaken with a purposeful
      sample of participants to explore patient experiences of both treatments.
      DISCUSSION: To our knowledge, this will be the first RCT to examine whether
      combining exercise with ACT produces greater benefit for patients with chronic
      pain, compared to a standalone supervised exercise programme. TRIAL REGISTRATION:
      www.ClinicalTrials.gov, ID: NCT03050528 . Registered on 13 February 2017.

PMID- 29566745
TI  - Antibodies against chemokine receptors CXCR3 and CXCR4 predict progressive
      deterioration of lung function in patients with systemic sclerosis.
AB  - BACKGROUND: The chemokine receptors CXCR3 and CXCR4 are involved in the
      pathogenesis of fibrosis, a key feature of systemic sclerosis (SSc). It is
      hypothesized that immunoglobulin (Ig)G antibodies (abs) against these two
      receptors are present in patients with SSc and are associated with clinical
      findings. METHODS: Anti-CXCR3 and anti-CXCR4 ab levels were measured in 449 sera
      from 327 SSc patients and in 234 sera from healthy donors (HD) by enzyme-linked
      immunosorbent assay (ELISA). In SSc, ab levels were compared with clinical data
      in a cross-sectional and longitudinal setting. Protein expression of CXCR3 and
      CXCR4 on peripheral blood mononuclear cells (PBMCs) was analyzed in 17 SSc
      patients and 8 HD by flow cytometry. RESULTS: Anti-CXCR3 and anti-CXCR4 ab levels
      were different among SSc subgroups compared with HD and were highest in diffuse
      SSc patients. The ab levels strongly correlated with each other (r = 0.85).
      Patients with SSc-related interstitial lung disease (SSc-ILD) exhibited higher ab
      levels which negatively correlated with lung function parameters (e.g., r = -0.5
      and r = -0.43 for predicted vital capacity, respectively). However, patients with
      deterioration of lung function showed lower anti-CXCR3/4 ab levels compared with
      those with stable disease. Frequencies and median fluorescence intensities (MFI)
      of CXCR3+ and CXCR4+ PBMCs were lower in SSc patients compared with HD and
      correlated with the severity of skin and lung fibrosis. They correlated with the
      severity of skin and lung fibrosis. CONCLUSIONS: Anti-CXCR3/4 abs and their
      corresponding receptors are linked with the severity of SSc-ILD. Antibody levels
      discriminate patients with stable or decreasing lung function and could be used
      for risk stratification.

PMID- 29566746
TI  - The influence of a consumer-wearable activity tracker on sedentary time and
      prolonged sedentary bouts: secondary analysis of a randomized controlled trial.
AB  - OBJECTIVE: A recent meta-analysis surmised pedometers were a useful panacea to
      independently reduce sedentary time (ST). To further test and expand on this
      deduction, we analyzed the ability of a consumer-wearable activity tracker to
      reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month
      randomized control trial where 800 employees from 13 organizations were assigned
      to control, activity tracker, or one of two activity tracker plus incentive
      groups designed to increase step count. The primary outcome was accelerometer
      measured moderate-to-vigorous physical activity. RESULTS: We conducted a
      secondary analysis on accelerometer measured daily ST and PSB bouts. A general
      linear mixed model was used to examine changes in ST and prolonged sedentary
      bouts, followed by between-group pairwise comparisons. Regression analyses were
      conducted to examine the association of changes in step counts with ST and PSB.
      The changes in ST and PSB were not statistically significant and not different
      between the groups (P < 0.05). Increases in step counts were concomitantly
      associated with decreases in ST and PSB, regardless of intervention (P < 0.05).
      Caution should be taken when considering consumer-wearable activity trackers as a
      means to reduce sedentary behavior. Trial registration NCT01855776 Registered:
      August 8, 2012.

PMID- 29566747
TI  - Correction to: Human umbilical cord mesenchymal stem cell conditioned medium
      attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal
      transition via the TLR4/NF-kappaB signaling pathway in vivo and in vitro.
AB  - The original article [1] contains an error whereby the corresponding authorship
      is mistakenly designated to the author Fengxia Ding.

PMID- 29566748
TI  - High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and
      butyrate production.
AB  - BACKGROUND: Changes in hygiene and dietary habits, including increased
      consumption of foods high in fat, simple sugars, and salt that are known to
      impact the composition and function of the intestinal microbiota, may explain the
      increase in prevalence of chronic inflammatory diseases. High salt consumption
      has been shown to worsen autoimmune encephalomyelitis and colitis in mouse models
      through p38/MAPK signaling pathway. However, the effect of high salt diet (HSD)
      on gut microbiota and on intestinal immune homeostasis, and their roles in
      determining vulnerability to intestinal inflammatory stimuli are unknown. Here,
      we investigate the role of gut microbiota alterations induced by HSD on the
      severity of murine experimental colitis. RESULTS: Compared to control diet, HSD
      altered fecal microbiota composition and function, reducing Lactobacillus sp.
      relative abundance and butyrate production. Moreover, HSD affected the colonic,
      and to a lesser extent small intestine mucosal immunity by enhancing the
      expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while
      suppressing many cytokine and chemokine genes, such as Ccl3, Ccl4, Cxcl2, Cxcr4,
      Ccr7. Conventionally raised mice fed with HSD developed more severe DSS- (dextran
      sodium sulfate) and DNBS- (dinitrobenzene sulfonic acid) induced colitis compared
      to mice on control diet, and this effect was absent in germ-free mice. Transfer
      experiments into germ-free mice indicated that the HSD-associated microbiota
      profile is critically dependent on continued exposure to dietary salt.
      CONCLUSIONS: Our results indicate that the exacerbation of colitis induced by HSD
      is associated with reduction in Lactobacillus sp. and protective short-chain
      fatty acid production, as well as changes in host immune status. We hypothesize
      that these changes alter gut immune homeostasis and lead to increased
      vulnerability to inflammatory insults.

PMID- 29566749
TI  - Immunotherapy for Merkel cell carcinoma: a turning point in patient care.
AB  - Merkel Cell carcinoma (MCC) is a rare but aggressive cancer, with an estimated
      disease-associated mortality as high as 46%. MCC has proven to be an
      immunologically responsive disease and the advent of immune checkpoint inhibitors
      has changed the treatment landscape for patients with advanced MCC. In this
      review, we discuss the rationale for the use of immune checkpoint inhibition,
      review current single agent therapies tested in and approved for MCC, and discuss
      emerging immunotherapeutic options for these patients.

PMID- 29566750
TI  - Predicting complications of major head and neck oncological surgery: an
      evaluation of the ACS NSQIP surgical risk calculator.
AB  - BACKGROUND: The American College of Surgeons National Surgical Quality
      Improvement Program (ACS NSQIP) universal surgical risk calculator is an online
      tool intended to improve the informed consent process and surgical decision
      making. The risk calculator uses a database of information from 585 hospitals to
      predict a patient's risk of developing specific postoperative outcomes. METHODS:
      Patient records at a major Canadian tertiary care referral center between July
      2015 and March 2017 were reviewed for surgical cases including one of six major
      head and neck oncologic surgeries: total thyroidectomy, total laryngectomy,
      hemiglossectomy, partial glossectomy, laryngopharyngectomy, and composite
      resection. Preoperative information for 107 patients was entered into the risk
      calculator and compared to observed postoperative outcomes. Statistical analysis
      of the risk calculator was completed for the entire study population, for
      stratification by procedure, and by utilization of microvascular reconstruction.
      Accuracy was assessed using the ratio of predicted to observed outcomes, Receiver
      Operating Characteristics (ROC), Brier score, and the Wilcoxon signed-ranked
      test. RESULTS: The risk calculator accurately predicted the incidences for 11 of
      12 outcomes for patients that did not undergo free flap reconstruction (NFF
      group), but was less accurate for patients that underwent free flap
      reconstruction (FF group). Length of stay (LOS) analysis showed similar results,
      with predicted and observed LOS statistically different in the overall population
      and FF group analyses (p = 0.001 for both), but not for the NFF group analysis (p
      = 0.764). All outcomes in the NFF group, when analyzed for calibration, met the
      threshold value (Brier scores < 0.09). Risk predictions for 8 of 12, and 10 of 12
      outcomes were adequately calibrated in the FF group and the overall study
      population, respectively. Analyses by procedure were excellent, with the risk
      calculator showing adequate calibration for 7 of 8 procedural categories and
      adequate discrimination for all calculable categories (6 of 6). CONCLUSION: The
      NSQIP-RC demonstrated efficacy for predicting postoperative complications in head
      and neck oncology surgeries that do not require microvascular reconstruction. The
      predictive value of the metric can be improved by inclusion of several factors
      important for risk stratification in head and neck oncology.

PMID- 29566751
TI  - Engineering a multicellular vascular niche to model hematopoietic cell
      trafficking.
AB  - BACKGROUND: The marrow microenvironment and vasculature plays a critical role in
      regulating hematopoietic cell recruitment, residence, and maturation. Extensive
      in vitro and in vivo studies have aimed to understand the marrow cell types that
      contribute to hematopoiesis and the stem cell environment. Nonetheless, in vitro
      models are limited by a lack of complex multicellular interactions, and cellular
      interactions are not easily manipulated in vivo. Here, we develop an engineered
      human vascular marrow niche to examine the three-dimensional cell interactions
      that direct hematopoietic cell trafficking. METHODS: Using soft lithography and
      injection molding techniques, fully endothelialized vascular networks were
      fabricated in type I collagen matrix, and co-cultured under flow with embedded
      marrow fibroblast cells in the matrix. Marrow fibroblast (mesenchymal stem cells
      (MSCs), HS27a, or HS5) interactions with the endothelium were imaged via confocal
      microscopy and altered endothelial gene expression was analyzed with RT-PCR.
      Monocytes, hematopoietic progenitor cells, and leukemic cells were perfused
      through the network and their adhesion and migration was evaluated. RESULTS:
      HS27a cells and MSCs interact directly with the vessel wall more than HS5 cells,
      which are not seen to make contact with the endothelial cells. In both HS27a and
      HS5 co-cultures, endothelial expression of junctional markers was reduced. HS27a
      co-cultures promote perfused monocytes to adhere and migrate within the vessel
      network. Hematopoietic progenitors rely on monocyte-fibroblast crosstalk to
      facilitate preferential recruitment within HS27a co-cultured vessels. In
      contrast, leukemic cells sense fibroblast differences and are recruited
      preferentially to HS5 and HS27a co-cultures, but monocytes are able to block this
      sensitivity. CONCLUSIONS: We demonstrate the use of a microvascular platform that
      incorporates a tunable, multicellular composition to examine differences in
      hematopoietic cell trafficking. Differential recruitment of hematopoietic cell
      types to distinct fibroblast microenvironments highlights the complexity of cell
      cell interactions within the marrow. This system allows for step-wise
      incorporation of cellular components to reveal the dynamic spatial and temporal
      interactions between endothelial cells, marrow-derived fibroblasts, and
      hematopoietic cells that comprise the marrow vascular niche. Furthermore, this
      platform has potential for use in testing therapeutics and personalized medicine
      in both normal and disease contexts.

PMID- 29566752
TI  - Affect, risk perception, and the use of cigarettes and e-cigarettes: a population
      study of U.S. adults.
AB  - BACKGROUND: Tobacco companies argue that the decision to smoke is made by well
      informed rational adults who have considered all the risks and benefits of
      smoking. Yet in promoting their products, the tobacco industry frequently relies
      on affect, portraying their products as part of a desirable lifestyle. Research
      examining the roles of affect and perceived risks in smoking has been scant and
      non-existent for novel tobacco products, such as electronic cigarettes (e
      cigarettes). METHODS: We examined the relationship between affect, perceived
      risk, and current use for cigarettes and e-cigarettes in 2015 in a nationally
      representative sample of 5398 U.S. adults who were aware of e-cigarettes.
      RESULTS: Participants held various affective associations with tobacco products,
      and affect towards cigarettes was more negative than affect towards e-cigarettes.
      Using structural equation modeling (SEM), affect towards cigarettes and e
      cigarettes was associated with cigarette smoking and e-cigarette use
      respectively, and these associations were both direct and partially mediated by
      risk perceptions towards smoking and e-cigarette use. More positive affect
      towards cigarettes or e-cigarettes was associated with lower perceived risks,
      which in turn was associated with higher odds of being a current cigarette or e
      cigarette user. CONCLUSIONS: In developing models explaining tobacco use
      behavior, or in creating public communication campaigns aimed at curbing tobacco
      use, it is useful to focus not only on the reason based predictors, such as
      perceptions of risks and benefits, but also on affective predictors. Educational
      efforts aimed at further smoking reductions should highlight and reinforce
      negative images and associations with cigarettes.

PMID- 29566753
TI  - A physician targeted intervention improves prescribing in chronic heart failure
      in general medical units.
AB  - BACKGROUND: Despite strong evidence for beta-blockers and angiotensin-converting
      enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in chronic heart
      failure (CHF), they have been under-utilised especially in general medical units.
      We aim to evaluate the effectiveness and feasibility of a physician-targeted
      quality improvement intervention with education and feedback on the prescription
      of beta-blockers and ACEI/ARB for CHF management in an inpatient setting.
      METHODS: We conducted an interrupted time series study between January 2009 and
      February 2012. A two-stage intervention was implemented. Between November 2009
      and January 2011, a structured physician-oriented education program was
      undertaken. From February 2011, quarterly performance feedback was provided to
      each medical unit by a senior clinician. Medical notes of patients admitted with
      CHF under general medical units before and during the intervention were
      prospectively audited. Main outcomes were beta-blockers and ACEI/ARB prescription
      rates, and 180-day readmission rates for CHF. RESULTS: Four hundred and sixty
      eight patients were included in this study. Structured education program was
      associated with a significant rise in beta-blockers prescription rates from a
      baseline of 60 to 92% (p = 0.003), but a non-sustained rise in ACEI/ARB
      prescription. Regular performance feedback resulted in a further sustained
      increase in ACEI/ARB prescription rates from 62 to 93% (p = 0.028) and a positive
      trend for beta-blockers with rates maintained at 89%. There was a reduction in
      180-day readmission rates that correlated with the improvements in beta-blocker
      (p = 0.030) and ACEI/ARB (p = 0.035) prescription. CONCLUSION: Implementation of
      a structured education program with regular performance feedback was durable and
      was associated with improvements in appropriate prescribing and an observed
      decrease in CHF-related readmissions.

PMID- 29566754
TI  - A qualitative study of community perception and acceptance of biological
      larviciding for malaria mosquito control in rural Burkina Faso.
AB  - BACKGROUND: Vector and malaria parasite's rising resistance against pyrethroid
      impregnated bed nets and antimalarial drugs highlight the need for additional
      control measures. Larviciding against malaria vectors is experiencing a
      renaissance with the availability of environmentally friendly and target species
      specific larvicides. In this study, we analyse the perception and acceptability
      of spraying surface water collections with the biological larvicide Bacillus
      thuringiensis israelensis in a single health district in Burkina Faso. METHODS: A
      total of 12 focus group discussions and 12 key informant interviews were
      performed in 10 rural villages provided with coverage of various larvicide
      treatments (all breeding sites treated, the most productive breeding sites
      treated, and untreated control). RESULTS: Respondents' knowledge about the major
      risk factors for malaria transmission was generally good. Most interviewees
      stated they performed personal protective measures against vector mosquitoes
      including the use of bed nets and sometimes mosquito coils and traditional
      repellents. The acceptance of larviciding in and around the villages was high and
      the majority of respondents reported a relief in mosquito nuisance and malarial
      episodes. There was high interest in the project and demand for future
      continuation. CONCLUSION: This study showed that larviciding interventions
      received positive resonance from the population. People showed a willingness to
      be involved and financially support the program. The positive environment with
      high acceptance for larviciding programs would facilitate routine implementation.
      An essential factor for the future success of such programs would be inclusion in
      regional or national malaria control guidelines.

PMID- 29566755
TI  - Conceptualisation and development of the Conversational Health Literacy
      Assessment Tool (CHAT).
AB  - BACKGROUND: The aim of this study was to develop a tool to support health
      workers' ability to identify patients' multidimensional health literacy strengths
      and challenges. The tool was intended to be suitable for administration in
      healthcare settings where health workers must identify health literacy priorities
      as the basis for person-centred care. METHODS: Development was based on a
      qualitative co-design process that used the Health Literacy Questionnaire (HLQ)
      as a framework to generate questions. Health workers were recruited to
      participate in an online consultation, a workshop, and two rounds of pilot
      testing. RESULTS: Participating health workers identified and refined ten
      questions that target five areas of assessment: supportive professional
      relationships, supportive personal relationships, health information access and
      comprehension, current health behaviours, and health promotion barriers and
      support. CONCLUSIONS: Preliminary evidence suggests that application of the
      Conversational Health Literacy Assessment Tool (CHAT) can support health workers
      to better understand the health literacy challenges and supportive resources of
      their patients. As an integrated clinical process, the CHAT can supplement
      existing intake and assessment procedures across healthcare settings to give
      insight into patients' circumstances so that decisions about care can be tailored
      to be more appropriate and effective.

PMID- 29566756
TI  - Vaginal health and hygiene practices and product use in Canada: a national cross
      sectional survey.
AB  - BACKGROUND: The vaginal microbiome influences quality of life and health. The
      composition of vaginal microbiota can be affected by various health behaviors,
      such as vaginal douching. The purpose of this study was to examine the types and
      prevalence of diverse vaginal/genital health and hygiene behaviors among
      participants living in Canada and to examine associations between behavioral
      practices and adverse gynecological health conditions. METHOD: An anonymous
      online survey, available in English and French, was distributed across Canada.
      The sample consisted of 1435 respondents, 18 years or older, living in Canada.
      RESULTS: Respondents reported engaging in diverse vaginal/genital health and
      hygiene behavioral practices, including the use of commercially manufactured
      products and homemade and naturopathic products and practices. Over 95% of
      respondents reported using at least one product in or around the vaginal area.
      Common products and practices included vaginal/genital moisturizers, anti-itch
      creams, feminine wipes, washes, suppositories, sprays, powders, and waxing and
      shaving pubic hair. The majority of the sample (80%) reported experiencing one or
      more adverse vaginal/genital symptom in their lifetime. Participants who had used
      any vaginal/genital product(s) had approximately three times higher odds of
      reporting an adverse health condition. Several notable associations between
      specific vaginal/genital health and hygiene products and adverse health
      conditions were identified. CONCLUSIONS: This study is the first of its kind to
      identify the range and prevalence of vaginal/genital health and hygiene behaviors
      in Canada. Despite a lack of credible information about the impact of these
      behaviors on women's health, the use of commercially manufactured and homemade
      products for vaginal/genital health and hygiene is common. Future research can
      extend the current exploratory study by identifying causal relationships between
      vaginal/genital health and hygiene behaviors and changes to the vaginal
      microbiome.

PMID- 29566758
TI  - Measurement and analysis of equity in health: a case study conducted in Zhejiang
      Province, China.
AB  - BACKGROUND: Equity is the core of primary care. The issue of equity in health has
      become urgent, and China has attached increasing attention to it. With rapid
      economic development and great changes in medical insurance policy, the pattern
      of equity in health has changed tremendously. The reform of healthcare in
      Zhejiang Province is at the forefront in China, and studies on Zhejiang Province
      are of great significance to the entire country. This paper aimed to measure
      health equity from the perspectives of health needs and health-seeking behavior
      and to provide suggestions for the next policy formulations, with respect to
      timeliness. METHODS: The investigator's household survey was conducted in August
      2016. A sample of 1000 households, which included2807 individuals in Zhejiang,
      China, was obtained with the multi-stage stratified cluster sampling method.
      Descriptive analysis and chi-square tests were adopted in the analysis. The value
      of the concentration index was used to measure the equity. RESULTS: This study
      found that the poor have more urgent health needs and poorer health situations
      than the rich. Through studies on health-seeking behavior, the utilization of
      outpatient services was almost equitable, while the utilization of
      hospitalization showed a pro-rich inequity (i.e., the rich use more services).
      Individuals with employer-based medical insurance used more outpatient services
      than those with rural and urban medical insurance. More people in the poorer
      income groups did not use inpatient services due to financial difficulties.
      CONCLUSIONS: Absolute medical prices and medical insurance may explain the equity
      in the utilization of outpatient services and the inequity in the utilization of
      hospitalization. In view of the pro-rich inequity of hospitalization, more
      financial protection should be provided for the poor.

PMID- 29566759
TI  - Impairment of microcirculation and vascular responsiveness in adolescents with
      primary Raynaud phenomenon.
AB  - BACKGROUND: Raynaud's phenomenon (RP) is a functional vascular disease,
      presenting with recurrent episodes of ischemia of extremities in response to cold
      and emotional stress. Investigating cutaneous microcirculation is an important
      tool in understanding the complex neuro-immuno-vascular interactions in its
      pathophysiological mechanisms. Since there is no available data on vascular
      responsiveness in RP in the paediatric population, we investigated skin perfusion
      and heat-induced hyperaemia in comparison with clinical severity and laboratory
      parameters of the disease. METHODS: Fifty two adolescents (27 patients with
      primary RP and 25 age-matched healthy controls) were investigated in the study.
      Patients were divided into two groups according to the symptoms existing within
      the previous 2 months. Following baseline microcirculation measurement with Laser
      Doppler flowmetry (Periflux 5000 system), all subjects underwent local heating
      test at 42  degrees C and 44  degrees C. Besides routine laboratory parameters,
      immune-serological tests and the vasoactive sensory neuropeptides somatostatin
      and pituitary adenylate-cyclase activating polypeptide (PACAP) were measured.
      RESULTS: Baseline perfusion measured in perfusion units (PU) at 32  degrees C was
      significantly lower in symptomatic RP patients (97.6 +/- 22.4 PU) compared with
      both healthy volunteers (248.3 +/- 23.5 PU, p < 0.001) and RP patients without
      symptoms (187.4 +/- 24.9 PU, p < 0.05). After local heating to 42  degrees C
      maximum blood flow was significantly reduced in primary RP participants with
      current symptoms (358.6 +/- 43.9 PU, p < 0.001), but not in asymptomatic ones
      (482.3 +/- 28.7 PU, p > 0.05) when compared with healthy subjects (555.9 +/- 28.2
      PU). Both the area under the response curve and the latency to reach the maximum
      flow were significantly increased in both RP groups (symptomatic 164.6 +/- 7.4 s,
      p < 0.001, asymptomatic 236.4 +/- 17.4 s, p < 0.001) when compared with the
      control group (101.9 +/- 4.7 s). The heat-induced percentage increase from
      baseline to maximal blood flow was significantly greater in symptomatic RP
      adolescents in comparison with healthy ones. Laboratory parameters and
      neuropeptide plasma levels were not altered in any groups. CONCLUSION: To our
      knowledge this is the first study in paediatric population to show altered heat
      induced cutaneous hyperaemia responses in relation with the clinical severity and
      symptomatology.

PMID- 29566760
TI  - Vascular biosafety of commercial hydroxyapatite particles: discrepancy between
      blood compatibility assays and endothelial cell behavior.
AB  - BACKGROUND: Vascular homeostasis is ensured by a dynamic interplay involving the
      endothelium, the platelets and the coagulation system. Thus, the vascular safety
      of particulate materials must address this integrated system, an approach that
      has been largely neglected. This work analysed the effects of commercial
      hydroxyapatite (HA) particles in blood compatibility and in endothelial cell
      behavior, due to their clinical relevance and scarcity of data on their vascular
      biosafety. RESULTS: Particles with similar chemical composition and distinct size
      and morphology were tested, i.e. rod-like, nano dimensions and low aspect ratio
      (HAp1) and needle-shape with wider size and aspect ratio (HAp2). HAp1 and HAp2,
      at 1 to 10 mg/mL, did not affect haemolysis, platelet adhesion, aggregation and
      activation, or the coagulation system (intrinsic and extrinsic pathways),
      although HAp2 exhibited a slight thrombogenic potential at 10 mg/mL.
      Notwithstanding, significantly lower levels presented dose-dependent toxicity on
      endothelial cells' behavior. HAp1 and HAp2 decreased cell viability at levels >=
      250 and >= 50 MUg/mL, respectively. At 10 and 50 MUg/mL, HAp1 did not interfere
      with the F-actin cytoskeleton, apoptotic index, cell cycle progression,
      expression of vWF, VECad and CD31, and the ability to form a network of tubular
      like structures. Comparatively, HAp2 caused dose-dependent toxic effects in these
      parameters in the same concentration range. CONCLUSION: The most relevant
      observation is the great discrepancy of HA particles' levels that interfere with
      the routine blood compatibility assays and the endothelial cell behavior.
      Further, this difference was also found to be dependent on the particles' size,
      morphology and aspect ratio, emphasizing the need of a complementary biological
      characterization, taking into consideration the endothelial cells' functionality,
      to establish the vascular safety of particulate HA.

PMID- 29566757
TI  - Molecular mechanism of diabetic cardiomyopathy and modulation of microRNA
      function by synthetic oligonucleotides.
AB  - Diabetic cardiomyopathy (DCM) is a chronic complication in individuals with
      diabetes and is characterized by ventricular dilation and hypertrophy, diastolic
      dysfunction, decreased or preserved systolic function and reduced ejection
      fraction eventually resulting in heart failure. Despite being well characterized,
      the fundamental mechanisms leading to DCM are still elusive. Recent studies
      identified the involvement of small non-coding small RNA molecules such as
      microRNAs (miRs) playing a key role in the etiology of DCM. Therefore, miRs
      associated with DCM represents a new class of targets for the development of
      mechanistic therapeutics, which may yield marked benefits compared to other
      therapeutic approaches. Indeed, few miRs currently under active clinical
      investigation, with many expressing cautious optimism that miRs based therapies
      will succeed in the coming years. The major caution in using miRs based therapy
      is the need to improve the stability and specificity following systemic
      injection, which can be achieved through chemical and structural modification. In
      this review, we first discuss the established role of miRs in DCM and the
      advances in miRs based therapeutic strategies for the prevention/treatment of
      DCM. We next discuss the currently employed chemical modification of miR
      oligonucleotides and their utility in therapies specifically focusing on the DCM.
      Finally, we summarize the commonly used delivery system and approaches for
      assessment of miRNA modulation and potential off-target effects.

PMID- 29566761
TI  - The expression profile of human peripheral blood mononuclear cell miRNA is
      altered by antibody-dependent enhancement of infection with dengue virus serotype
      3.
AB  - BACKGROUND: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection
      has been identified as the main risk factor for severe dengue disease, although
      the underlying mechanisms leading to severe dengue fever remain unclear.
      MicroRNAs (miRNAs) participate in numerous pathological and biological processes,
      including host responses to viral infections. METHOD: Here, we aimed to
      investigate the differences in miRNA expression patterns in human peripheral
      blood mononuclear cells (PBMCs) infected with DENV-3 and DENV-3-ADE at various
      time points employing high-throughput sequencing. RESULTS: According to miRNAs
      high-throughput sequencing, a total of 50 known miRNAs exhibited significant
      differences. GO (Gene Ontology) and pathway analysis of the predicted targets
      showed enrichment in the regulation of transcription, including multicellular
      organismal development, DNA-dependent transcription, negative regulation of cell
      differentiation and transcription. Afterwards, regulatory networks of miRNA
      predicted targets, miRNA transcription factors, miRNA pathways and miRNA GOs were
      formulated to expose the complex regulatory mechanisms of miRNAs during the
      infection phase. Finally, we analyzed hierarchical GO categories of the predicted
      targets involved in the MAPK signaling pathway, the cGMP-PKG signaling pathway,
      the cAMP signaling pathway, the endocytosis effect, and our analyses indicated
      that innate and adaptive immunity following DENV-3 and DENV-3-ADE infections may
      be signally distinct. CONCLUSION: Our results demonstrate a novel describing
      miRNA expression profiles in human PBMCs with DENV-3 and DENV-3-ADE infections
      using high-throughput sequencing. Our findings could provide a beneficial basis
      for further studies on the regulatory roles of miRNAs relevant to the different
      immune responses caused by DENV-3 and DENV-3-ADE infections.

PMID- 29566763
TI  - Comparing fiberoptic bronchoscopy and a tracheal tube-mounted camera-guided
      percutaneous dilatational tracheostomy: authors' reply.

PMID- 29566762
TI  - Partial breast irradiation with CyberKnife after breast conserving surgery: a
      pilot study in early breast cancer.
AB  - BACKGROUND: Local recurrences after breast conserving treatment are mainly close
      to the original tumor site, and as such shorter fractionation strategies focused
      on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI),
      have been developed. Stereotactic APBI has been attempted, although there is
      little experience using CyberKnife (CK) for early breast cancer. METHODS: This
      pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable
      patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub
      acute toxicity; secondary endpoints were late toxicity and the cosmetic result.
      RESULTS: Mean pathological tumor size was 10.5 mm (+/-4.3, range 3-18), 8 of
      these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2
      enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min
      (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to
      the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a
      median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median
      PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and
      V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37),
      respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3
      29.3). Mild side effects were recorded during the period of observation. Cosmetic
      evaluations were performed by three observers from the start of radiotherapy up
      to 2 years. Patients' evaluation progressively increase from 60% to 85% of
      excellent rating; this trend was similar to that of external observer.
      CONCLUSIONS: These preliminary results showed the safe feasibility of CK-APBI in
      early breast cancer, with mild acute and late toxicity and very good cosmetic
      results. TRIAL REGISTRATION: The present study is registered at Clinicaltrial.gov
      ( NCT02896322 ). Retrospectively egistered August 4, 2016.

PMID- 29566764
TI  - Do we need new trials of procalcitonin-guided antibiotic therapy? A response.

PMID- 29566765
TI  - Rheumatology in East Asia.
AB  - Europe and North America have been leaders in rheumatology for many years.
      However, for more than a decade now the East Asian region has been catching up
      dramatically. Some aspects of rheumatology in East Asia are now almost comparable
      to those in the European League Against Rheumatism (EULAR) and the American
      College of Rheumatology (ACR). In this article, we describe recent progress in
      rheumatology in East Asia, focusing specifically on Japan, Korea, and China.

PMID- 29566766
TI  - A customized home-based computerized cognitive rehabilitation platform for
      patients with chronic-stage stroke: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Stroke patients usually suffer primary cognitive impairment related
      to attention, memory, and executive functions. This impairment causes a negative
      impact on the quality of life of patients and their families, and may be long
      term. Cognitive rehabilitation has been shown to be an effective way to treat
      cognitive impairment and should be continued after hospital discharge.
      Computerized cognitive rehabilitation can be performed at home using exercise
      programs that advance with predetermined course content, interval, and pace. We
      hypothesize that computerized rehabilitation might be improved if a program could
      customize course content and pace in response to patient-specific progress. The
      present pilot study is a randomized controlled double-blind crossover clinical
      trial aiming to study if chronic stroke patients with cognitive impairment could
      benefit from cognitive training through a customized tele-rehabilitation platform
      ("Guttmann, NeuroPersonalTrainer"(r), GNPT(r)). METHODS/DESIGN: Individuals with
      chronic-stage stroke will be recruited. Participants will be randomized to
      receive experimental intervention (customized tele-rehabilitation platform,
      GNPT(r)) or sham intervention (ictus.online), both with the same frequency and
      duration (five sessions per week over 6 weeks). After a washout period of 3
      months, crossover will occur and participants from the GNPT(r) condition will
      receive sham intervention, while participants originally from the sham
      intervention will receive GNPT(r). Patients will be assessed before and after
      receiving each treatment regimen with an exhaustive neuropsychological battery.
      Primary outcomes will include rating measures that assess attention difficulties,
      memory failures, and executive dysfunction for daily activities, as well as
      performance-based measures of attention, memory, and executive functions.
      DISCUSSION: Customized cognitive training could lead to better cognitive function
      in patients with chronic-stage stroke and improve their quality of life. TRIAL
      REGISTRATION: NCT03326349 . Registered 31 October 2017.

PMID- 29566767
TI  - Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce
      apoptosis on rheumatoid arthritis synovial fibroblasts.
AB  - BACKGROUND: Effects of methotrexate (MTX) on the proliferation of rheumatoid
      arthritis (RA) synovial fibroblasts are incompletely understood. We explored
      actions of MTX in view of circadian transcriptions of synovial fibroblasts.
      METHODS: Under treatment with MTX, expression of core circadian clock genes,
      circadian transcriptional factor proline and acidic amino acid-rich basic leucine
      zipper (PAR bZIP), and proapoptotic molecule Bcl-2 interacting killer (Bik) was
      examined by real-time polymerase chain reaction. Protein expression of circadian
      clock gene PERIOD2 (PER2) and CYTOCHROME C was also examined by western blotting
      and ELISA. Promoter activities of Per2 and Bik were measured by Luciferase assay.
      Expression of PER2, BIK, and CYTOCHROME C and morphological changes of the
      nucleus were observed by fluorescent immunostaining. Synovial fibroblasts were
      transfected with Per2/Bik small interfering RNA, and successively treated with
      MTX to determine cell viabilities. Finally, synovial fibroblasts were treated
      with MTX according to the oscillation of Per2/Bik expression. RESULTS: MTX (10
      nM) significantly decreased cell viabilities, but increased messenger RNA
      expression of Per2, Bik, and PAR ZIP including D site of the albumin promoter
      binding protein (Dbp), hepatic leukemia factor (Hlf), and thyrotroph embryonic
      factor (Tef). MTX also increased protein expression of PER2 and CYTOCHROME C, and
      promoter activities of Per2 and Bik via D-box. Under fluorescent observations,
      expression of PER2, BIK, and CYTOCHROME C was increased in apoptotic cells.
      Cytotoxicity of MTX was attenuated by silencing of Per2 and/or Bik, and revealed
      that MTX was significantly effective in situations where Per2/Bik expression was
      high. CONCLUSIONS: We present here novel unique action of MTX on synovial
      fibroblasts that upregulates PAR bZIP to transcribe Per2 and Bik, resulting in
      apoptosis induction. MTX is important in modulating circadian environments to
      understand a new aspect of pathogenesis of RA.

PMID- 29566769
TI  - Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study.
AB  - BACKGROUND: Tofacitinib is the first oral Janus kinase inhibitor approved for the
      treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety
      of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis
      factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously
      treated with methotrexate. METHODS: We used MarketScan(r) databases (2011-2014)
      to study methotrexate-exposed patients with RA who were newly prescribed
      tofacitinib, DMARDs other than methotrexate, and biologics. The date of first
      prescription was defined as the cohort entry. The therapy was considered
      effective if all of the following criteria from a claims-based algorithm were
      achieved at the first year of follow-up: high adherence, no biologic or
      tofacitinib switch or addition, no DMARD switch or addition, no increase in dose
      or frequency of index drug, no more than one glucocorticoid joint injection, and
      no new/increased oral glucocorticoid dose. The safety outcome was serious
      infections requiring hospitalization. Non-TNF biologics comprised the reference
      group. RESULTS: We included 21,832 patients with RA, including 0.8% treated with
      tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with
      TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy
      effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and
      19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF
      biologics appeared to have similar effectiveness rates, whereas DMARD initiators
      were less effective than non-TNF biologics. We could not clearly establish if
      tofacitinib was associated with a higher rate of serious infections. CONCLUSIONS:
      In patients with RA previously treated with methotrexate, our comparisons of
      tofacitinib with non-TNF biologics, though not definitive, did not demonstrate
      differences with respect to hospitalized infections or effectiveness.

PMID- 29566768
TI  - Functional genomics identifies specific vulnerabilities in PTEN-deficient breast
      cancer.
AB  - BACKGROUND: Phosphatase and tensin homolog (PTEN) is one of the most frequently
      inactivated tumor suppressors in breast cancer. While PTEN itself is not
      considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL)
      genes are potential drug targets in PTEN-deficient breast cancers. Therefore,
      with the aim of identifying potential targets for precision breast cancer
      therapy, we sought to discover PTEN-SSL genes present in a broad spectrum of
      breast cancers. METHODS: To discover broad-spectrum PTEN-SSL genes in breast
      cancer, we used a multi-step approach that started with (1) a genome-wide short
      interfering RNA (siRNA) screen of ~ 21,000 genes in a pair of isogenic human
      mammary epithelial cell lines, followed by (2) a short hairpin RNA (shRNA) screen
      of ~ 1200 genes focused on hits from the first screen in a panel of 11 breast
      cancer cell lines; we then determined reproducibility of hits by (3)
      identification of overlaps between our results and reanalyzed data from 3
      independent gene-essentiality screens, and finally, for selected candidate PTEN
      SSL genes we (4) confirmed PTEN-SSL activity using either drug sensitivity
      experiments in a panel of 19 cell lines or mutual exclusivity analysis of
      publicly available pan-cancer somatic mutation data. RESULTS: The screens (steps
      1 and 2) and the reproducibility analysis (step 3) identified six candidate broad
      spectrum PTEN-SSL genes (PIK3CB, ADAMTS20, AP1M2, HMMR, STK11, and NUAK1). PIK3CB
      was previously identified as PTEN-SSL, while the other five genes represent novel
      PTEN-SSL candidates. Confirmation studies (step 4) provided additional evidence
      that NUAK1 and STK11 have PTEN-SSL patterns of activity. Consistent with PTEN-SSL
      status, inhibition of the NUAK1 protein kinase by the small molecule drug HTH-01
      015 selectively impaired viability in multiple PTEN-deficient breast cancer cell
      lines, while mutations affecting STK11 and PTEN were largely mutually exclusive
      across large pan-cancer data sets. CONCLUSIONS: Six genes showed PTEN-SSL
      patterns of activity in a large proportion of PTEN-deficient breast cancer cell
      lines and are potential specific vulnerabilities in PTEN-deficient breast cancer.
      Furthermore, the NUAK1 PTEN-SSL vulnerability identified by RNA interference
      techniques can be recapitulated and exploited using the small molecule kinase
      inhibitor HTH-01-015. Thus, NUAK1 inhibition may be an effective strategy for
      precision treatment of PTEN-deficient breast tumors.

PMID- 29566770
TI  - Stem cell properties of human clonal salivary gland stem cells are enhanced by
      three-dimensional priming culture in nanofibrous microwells.
AB  - BACKGROUND: Three-dimensional (3D) cultures recapitulate the microenvironment of
      tissue-resident stem cells and enable them to modulate their properties. We
      determined whether salivary gland-resident stem cells (SGSCs) are primed by a 3D
      spheroid culture prior to treating irradiation-induced salivary hypofunction
      using in-vitro coculture and in-vivo transplant models. METHODS: 3D spheroid
      derived SGSCs (SGSCs3D) were obtained from 3D culture in microwells consisting of
      a nanofiber bottom and cell-repellent hydrogel walls, and were examined for
      salivary stem or epithelial gene/protein expression, differentiation potential,
      and paracrine secretory function compared with monolayer-cultured SGSCs (SGSCs2D)
      in vitro and in vivo. RESULTS: SGSCs3D expressed increased salivary stem cell
      markers (LGR5 and THY1) and pluripotency markers (POU5F1 and NANOG) compared with
      SGSCs2D. Also, SGSCs3D exhibited enhanced potential to differentiate into
      salivary epithelial cells upon differentiation induction and increased paracrine
      secretion as compared to SGSCs2D. Wnt signaling was activated by 3D spheroid
      formation in the microwells and suppression of the Wnt/beta-catenin pathway led
      to reduced stemness of SGSCs3D. Enhanced radioprotective properties of SGSCs3D
      against radiation-induced salivary hypofunction was confirmed by an organotypic
      3D coculture and in-vivo transplantation experiments. CONCLUSION: The 3D spheroid
      culture of SGSCs in nanofibrous microwells promotes stem cell properties via
      activation of Wnt signaling. This may contribute to SGSC priming prior to
      regenerative therapy to restore salivary hypofunction after radiotherapy.

PMID- 29566771
TI  - Microbiota inoculum composition affects holobiont assembly and host growth in
      Daphnia.
AB  - BACKGROUND: Host-associated microbiota is often acquired by horizontal
      transmission of microbes present in the environment. It is hypothesized that
      differences in the environmental pool of colonizers can influence microbiota
      community assembly on the host and as such affect holobiont composition and host
      fitness. To investigate this hypothesis, the host-associated microbiota of the
      invertebrate eco(toxico)logical model Daphnia was experimentally disturbed using
      different concentrations of the antibiotic oxytetracycline. The community
      assembly and host-microbiota interactions when Daphnia were colonized by the
      disturbed microbiota were investigated by inoculating germ-free individuals with
      the microbiota. RESULTS: Antibiotic-induced disturbance of the microbiota had a
      strong effect on the subsequent colonization of Daphnia by affecting ecological
      interactions between members of the microbiota. This resulted in differences in
      community assembly which, in turn, affected Daphnia growth. CONCLUSIONS: These
      results show that the composition of the pool of colonizing microbiota can be an
      important structuring factor of the microbiota assembly on Daphnia, affecting
      holobiont composition and host growth. These findings contribute to a better
      understanding of how the microbial environment can shape the holobiont
      composition and affect host-microbiota interactions.

PMID- 29566773
TI  - Psychotic-like experiences with cannabis use predict cannabis cessation and
      desire to quit: a cannabis discontinuation hypothesis.
AB  - BACKGROUND: Evidence suggests that cannabis-induced psychotic-like experiences
      may be a marker of psychosis proneness. The effect of such experiences on
      cannabis use has not systematically been examined. METHODS: We undertook a mixed
      methods online survey of 1231 cannabis users (including 926 continued users)
      using the Cannabis Experiences Questionnaire. We examined the effect of psychotic
      like and pleasurable experiences on cessation of cannabis and intention to quit.
      Socio-demographic variables, cannabis use parameters and substance misuse history
      were included as covariates. Free-text data explored subjective reasons for
      changes in use. RESULTS: Cessation of cannabis use was associated with greater
      psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI)
      1.179-1.351], whilst continued cannabis users were more likely to report
      pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662-0.776]. Intention
      to quit cannabis in continued users was associated with greater psychotic-like
      experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044-1.225], whilst intention to
      not quit was significantly associated with increased pleasurable experiences [p <
      0.015, Exp(B) 0.892, 95% CI 0.814-0.978]. Whereas former users clearly ascribed
      cessation to negative experiences, continued users who expressed intention to
      quit less readily ascribed the intention to negative experiences. CONCLUSIONS:
      Elucidation of psychotic-like experiences may form the basis of a therapeutic
      intervention for those who wish to quit. Cessation in those with cannabis-induced
      psychotomimetic experiences may offset the risk for the development of a
      psychotic disorder, in this higher risk group.

PMID- 29566772
TI  - Platelet lysate as a novel serum-free media supplement for the culture of equine
      bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) produced for clinical purposes rely on
      culture media containing fetal bovine serum (FBS) which is xenogeneic and has the
      potential to significantly alter the MSC phenotype, rendering these cells
      immunogenic. As a result of bovine-derived exogenous proteins expressed on the
      cell surface, MSCs may be recognized by the host immune system as non-self and be
      rejected. Platelet lysate (PL) may obviate some of these concerns and shows
      promising results in human medicine as a possible alternative to FBS. Our goal
      was to evaluate the use of equine platelet lysate (ePL) pooled from donor horses
      in place of FBS to culture equine MSCs. We hypothesized that ePL, produced
      following apheresis, will function as the sole media supplement to accelerate the
      expansion of equine bone marrow-derived MSCs without altering their phenotype and
      their immunomodulatory capacity. METHODS: Platelet concentrate was obtained via
      plateletpheresis and ePL were produced via freeze-thaw and centrifugation cycles.
      Population doublings (PD) and doubling time (DT) of bone marrow-derived MSCs (n =
      3) cultured with FBS or ePL media were calculated. Cell viability,
      immunophenotypic analysis, and trilineage differentiation capacity of MSCs were
      assessed accordingly. To assess the ability of MSCs to modulate inflammatory
      responses, E. coli lipopolysaccharide (LPS)-stimulated monocytes were cocultured
      with MSCs cultured in the two different media formulations, and cell culture
      supernatants were assayed for the production of tumor necrosis factor (TNF)
      alpha. RESULTS: Our results showed that MSCs cultured in ePL media exhibited
      similar proliferation rates (PD and DT) compared with those cultured in FBS at
      individual time points. MSCs cultured in ePL showed a statistically significant
      increased viability following a single washing step, expressed similar levels of
      MSC markers compared to FBS, and were able to differentiate towards the three
      lineages. Finally, MSCs cultured in ePL efficiently suppressed the release of TNF
      alpha when exposed to LPS-stimulated monocytes similar to those cultured in FBS.
      CONCLUSION: ePL has the potential to be used for the expansion of MSCs before
      clinical application, avoiding the concerns associated with the use of FBS.

PMID- 29566774
TI  - Detresse chez les preposes aux beneficiaires en centre d'hebergement exposes a
      des symptomes comportementaux.
AB  - ABSTRACTCare aides working in nursing homes are often exposed to responsive
      behaviours in older adults living with Alzheimer's disease. As these behaviors
      may induce psychological distress, the current research aims to estimate the
      contribution of a set of variables on the psychological distress reported by care
      aides. Variables include perceived frequency of responsive behaviours, primary
      and secondary cognitive appraisal, and coping strategies. A total of ninety-two
      day care aides were recruited in nursing homes in the Quebec City area. Standard
      multiple regression was completed and findings show that frequency of responsive
      behaviours, primary appraisal of threat, secondary appraisal (feeling incapable
      of changing the situation) and seeking emotional support contribute to care
      aides' psychological distress. This study highlights the importance of responsive
      behaviours on the units and discusses the psychological mechanisms used by care
      aides.

PMID- 29566775
TI  - Food Crises and Food Safety Incidents in European Union, United States, and
      Maghreb Area: Current Risk Communication Strategies and New Approaches.
AB  - Globalization has created a dynamic market, which has dramatically intensified
      interchanges of goods and information as well as the flow of people among
      nations. This international phenomenon offers the consumer a choice between a
      wide variety of foods from diverse locations. However, there are challenges to
      improving food security and safety on a global scale; the major question is how
      food safety can be guaranteed while increasing the complexity of food supply
      chains. A food produced in a certain location usually contains ingredients,
      additives, and preservatives from different and distant origins. Although
      countries take several food control measures, their institutional and regulatory
      frameworks diverge widely, as do the definitions of food crisis, food incidents,
      and risk management approaches. The present review discusses some past food
      safety issues and lessons learned. Convergences and differences in the regulatory
      framework of food control agencies in different regions of the world are herein
      revealed. Emerging risks are also discussed, particularly the spread of
      antibiotic resistance in the food chain and the environment, as well as the rise
      of new antibiotic-resistant pathogenic strains with broader tolerance to
      environmental factors.

PMID- 29566776
TI  - Vitamin D Dietary Supplementation: Relationship with Chronic Heart Failure.
AB  - It is estimated that over 1 billion people worldwide have a deficiency of vitamin
      D, also known as hypovitaminosis D, which the World Health Organization has
      defined as a public health problem. Beyond its historical homeostasis regulatory
      function of calcium and phosphorus, in relation to the preservation of the
      skeletal system, several studies show today a close connection between
      hypovitaminosis D and the genesis of rheumatic, autoimmune, neoplastic, and
      cardiovascular diseases. With exclusive reference to cardiovascular aspects,
      multiple heart diseases such as hypertension, myocardial ischemia, and heart
      failures might have deficiency in vitamin D as an important causative factor.
      Because of the influence of concomitant pathologies caused by antibiotic
      resistant agents, the function of this vitamin should be critically evaluated.
      However, the role of vitamin D remains to be established; only a few studies have
      tested the effects of its supplementation in patients with chronic heart failure
      diseases, and reported results are unclear. It is important to implement studies
      in this field in order to assess the real benefits induced by vitamin D
      supplementation in cardiovascular patients and, in particular, in patients with
      heart failure. Should the research confirm actual clinical improvement after
      treatment with vitamin D, such a supplementation might represent a new low-cost
      therapeutic approach to improving quality of life.

PMID- 29566777
TI  - Screening of 485 Pesticide Residues in Fruits and Vegetables by Liquid
      Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry Based on TOF Accurate
      Mass Database and QTOF Spectrum Library.
AB  - This paper uses the LC-quadrupole-time-of-flight MS technique to evaluate the
      behavioral characteristics of MS of 485 pesticides under different conditions and
      has developed an accurate mass database and spectra library. A high-throughput
      screening and confirmation method has been developed for the 485 pesticides in
      fruits and vegetables. Through the optimization of parameters such as accurate
      mass number, time of retention window, ionization forms, etc., the method has
      improved the accuracy of pesticide screening, thus avoiding the occurrence of
      false-positive and false-negative results. The method features a full scan of
      fragments, with 80% of pesticide qualitative points over 10, which helps increase
      pesticide qualitative accuracy. The abundant differences of fragment categories
      help realize the effective separation and qualitative identification of isomer
      pesticides. Four different fruits and vegetables-apples, grapes, celery, and
      tomatoes-were chosen to evaluate the efficiency of the method at three
      fortification levels of 5, 10, and 20 MUg/kg, and satisfactory results were
      obtained. With this method, a national survey of pesticide residues was conducted
      between 2012 and 2015 for 12 551 samples of 146 different fruits and vegetables
      collected from 638 sampling points in 284 counties across 31 provincial
      capitals/cities directly under the central government, which provided scientific
      data backup for ensuring pesticide residue safety of the fruits and vegetables
      consumed daily by the public. Meanwhile, the big data statistical analysis of the
      new technique also further proves it to be of high speed, high throughput, high
      accuracy, high reliability, and high informatization.

PMID- 29566779
TI  - Biennial Review of Planar Chromatography: 2015-2017.
AB  - The most important advances in planar chromatography published between November
      1, 2015, and November 1, 2017, are reviewed in this paper. Included are an
      introduction to the current status of the field; student experiments and reviews;
      apparatus and techniques for sample preparation and TLC separations; detection
      and identification of separated zones; quantitative analysis; preparative layer
      chromatography; and thin-layer radiochromatography. Selected applications are
      given in the various sections of the review.

PMID- 29566778
TI  - Identification and Assessment of the Behavior of Methicillin-Resistant
      Staphylococci in Cheese.
AB  - This study was carried out with the aim of identifying and assessing methicillin
      resistant Staphylococcus aureus (MRSA) during lactic acid cheese storage. The
      study involved 30 assortments of lactic acid cheese and 21 cheeses with S. aureus
      TWP11616 (MRSA). Results showed low MRSA contamination levels in lactic acid
      cheese. The majority of cow and goat lactic acid cheese samples (more than 72%)
      were characterized by a low level of MRSA (<=10 CFU/g). With regard to cow and
      sheep lactic acid cheese, methicillin-resistant Staphylococcus spp. contamination
      levels of >=100 CFU/g were found in 88 and 100% of samples, respectively. The
      microbial dynamics of MRSA changes in lactic acid cheese suggest a significant
      reduction in contamination levels after 4 days of product storage, and this
      decrease is likely not dependent on the type of packaging method.

PMID- 29566780
TI  - Analytical Approaches and Safety Evaluation Strategies for Antibiotics and
      Antimicrobial Agents in Food Products: Chemical and Biological Solutions.

PMID- 29566781
TI  - Mycobacterium tuberculosis, a cause of necrotising pneumonia in childhood: a case
      series.
AB  - SETTING: Tertiary care hospital, Western Cape, South Africa. DESIGN:
      Retrospective descriptive study of a case series of necrotising pneumonia (NP) in
      children associated with Mycobacterium tuberculosis presenting over a 4-year
      period in a country with high human immunodeficiency virus (HIV) and tuberculosis
      (TB) prevalence. OBJECTIVE: To describe the clinical and radiological features
      of, and treatment regimens and outcomes in, children with NP. RESULTS: Of 32
      children (median age 16.5 months, interquartile range 10-33), 8 (25%) (median age
      49 months) had NP associated with M. tuberculosis, 6 of whom were HIV-infected.
      Chest computed tomography (CT) was diagnostic in all cases: no radiological signs
      were suggestive of TB. There was no difference in the clinical picture, chest
      radiography or CT scan between M. tuberculosis-associated and bacterial NP. M.
      tuberculosis was cultured in 75% of cases; pleural fluid acid-fast bacilli was
      positive in an additional two cases. Surgery was required in 46% of the M.
      tuberculosis cases. At follow-up, 50% of these cases had complete radiological
      resolution similar to bacterial NP. CONCLUSION: This series highlights the fact
      that M. tuberculosis not only causes acute pneumonia in children, it also results
      in numerous complications. M. tuberculosis should be considered as a cause of NP
      in all children, especially HIV-infected children, living in high TB prevalence
      regions.

PMID- 29566782
TI  - Are LOD and LOQ Reliable Parameters for Sensitivity Evaluation of Spectroscopic
      Methods?
AB  - The limit of detection (LOD) and the limit of quantification (LOQ) are common
      parameters to assess the sensitivity of analytical methods. In this study, the
      LOD and LOQ of previously reported terbium sensitized analysis methods were
      calculated by different methods, and the results were compared with sensitivity
      parameters [lower limit of quantification (LLOQ)] of U.S. Food and Drug
      Administration guidelines. The details of the calibration curve and standard
      deviation of blank samples of three different terbium-sensitized luminescence
      methods for the quantification of mycophenolic acid, enrofloxacin, and silibinin
      were used for the calculation of LOD and LOQ. A comparison of LOD and LOQ values
      calculated by various methods and LLOQ shows a considerable difference. The
      significant difference of the calculated LOD and LOQ with various methods and
      LLOQ should be considered in the sensitivity evaluation of spectroscopic methods.

PMID- 29566783
TI  - Validation and Measurement Uncertainty Assessment of a Microbiological Method
      Using Generalized Pivotal Quantity Procedure and Monte-Carlo Simulation.
AB  - Recently, a novel and effective statistical tool called the uncertainty profile
      has been developed with the purpose of graphically assessing the validity and
      estimating the measurement uncertainty of analytical procedures. One way to
      construct the uncertainty profile is to compute the beta-content, gamma
      confidence tolerance interval. In this study, we propose a tolerance interval
      based on the combination of the generalized pivotal quantity procedure and Monte
      Carlo simulation. The uncertainty profile has been applied successfully in
      several fields. However, in order to further confirm its universality, this newer
      approach has been applied to assess the performance of an alternative procedure
      versus a reference procedure for counting of Escherichia coli bacteria in
      drinking water. Hence, the aims of this research were to expose how the
      uncertainty profile can be powerfully applied pursuant to ISO 16140 standards in
      the frame of interlaboratory study and how to easily make a decision concerning
      the validity of the procedure. The analysis of the results shows that after the
      introduction of a correction factor, the alternative procedure is deemed valid
      over the studied range because the uncertainty limits lie within the
      acceptability limits set at +/--0.3 log unit/100 ml for a beta = 66.7% and gamma
      = 90%.

PMID- 29566784
TI  - Antioxidant ?-cryptoxanthin enhances porcine oocyte maturation and subsequent
      embryo development in vitro.
AB  - Oxidative stress is partly responsible for the poor quality of IVM oocytes. The
      present study investigated the effects of the antioxidant beta-cryptoxanthin on
      the IVM of porcine oocytes and the in vitro development of the ensuing embryos.
      Oocytes were matured in IVM medium containing different concentrations of beta
      cryptoxanthin (0, 0.1, 1, 10 or 100MUM). Treatment with 1uM beta-cryptoxanthin
      (Group 1B) improved polar body extrusion and the expression of maturation-related
      genes in cumulus cells and oocytes compared with control. In addition, levels of
      reactive oxygen species decreased significantly in Group 1B, whereas there were
      significant increases in glutathione levels and expression of the antioxidant
      genes superoxide dismutase 1 and peroxiredoxin 5 in this group. After
      parthenogenetic activation, although the cleavage rate did not differ between the
      control and 1B groups, the blastocyst formation rate was higher in the latter.
      Moreover, the total number of cells per blastocyst and relative mRNA levels of
      pluripotency marker and antioxidant genes were significantly higher in the 1B
      compared with control group. These results demonstrate that beta-cryptoxanthin
      decreases oxidative stress in porcine oocytes and improves their quality and
      developmental potential.

PMID- 29566786
TI  - 30 Years and Counting.

PMID- 29566785
TI  - Temporally differential protein expression of glycolytic and glycogenic enzymes
      during in vitro preimplantation bovine embryo development.
AB  - Proteomic analyses are useful for understanding the metabolic pathways governing
      embryo development. This study investigated the presence of enzymes involved in
      glycolysis and glycogenesis in in vitro-produced bovine embryos at five
      developmental stages leading up to blastocyst formation. The enzymes examined
      were: (1) glycolytic: hexokinase-I (HK-I), phosphofructokinase-1 (PFK-1),
      pyruvate kinase mutase 1/2 (PKM-1/2), glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and (2) glycogenic: glycogen synthase kinase-3 isoforms alpha/ beta (GSK
      3alpha/beta). Glucose transporter-1 (GLUT-1) was also analysed. The developmental
      stages examined were: (1) 2-4-cell, (2) 5-8-cell, (3) 16-cell, (4) morula and (5)
      expanded blastocyst. The enzymes HK-I, PFK-1, PKM-1/2, GAPDH and GLUT-1 were
      differentially expressed throughout all stages (P<0.05). GSK-3alpha and beta were
      also differentially expressed from the 2-4-cell to the expanded blastocyst stage
      (P<0.05) and GLUT-1 was identified throughout. The general trend was that the
      abundance of PFK1, GAPDH and PKM-1/2 decreased whereas HK-I, phospho-GSK3alpha (P
      GSK3alpha) and P-GSK3beta levels increased as the embryo advanced. In contrast,
      GLUT-1 expression peaked at the 16-cell stage. These data combined suggest that
      in vitro bovine embryo metabolism switches from being glycolytic-centric to
      glycogenic-centric around the 16-cell stage, the developmental window also
      characterised by embryonic genome activation.

PMID- 29566787
TI  - Sleep, Anesthesia, and Plasticity.
AB  - Two theories continuously clash: does sleep downscale or potentiate synapses? A
      study in Neuron by Gonzalez-Rueda et al. (2018) demonstrates overall synaptic
      depression during anesthesia-induced slow-wave activity. Because anesthesia is
      typically associated with amnesia, the question of whether slow-wave sleep
      potentiates or depresses cortical synapses remains open.

PMID- 29566788
TI  - Tauomics and Kinetics in Human Neurons and Biological Fluids.
AB  - In this issue of Neuron, Sato et al. (2018) combine proteomics and a stable
      isotope labeling method to examine different forms of tau and their kinetics in
      human neurons, brain, and cerebrospinal fluid and how these properties relate to
      clinical state and pathology in Alzheimer's disease.

PMID- 29566789
TI  - An Old Neuron Learns New Tricks: Redefining Motion Processing in the Primate
      Retina.
AB  - Motion sensitivity requires the comparison of neural responses activated by
      nearby points in visual space. In this issue of Neuron, Manookin et al. (2018)
      find that in the primate retina, such comparisons are already manifest in second
      order retinal bipolar cells, relying on lateral excitation mediated by gap
      junctions.

PMID- 29566790
TI  - Dissecting Modulatory Effects of Visual Attention in Primate Lateral Prefrontal
      Cortex Using Signal Detection Theory.
AB  - In this issue of Neuron, Luo and Maunsell (2018) use signal detection theory to
      demonstrate that the modulatory effects of attention on neuronal responses in the
      lateral prefrontal cortex during change detection can be due to changes in an
      observer's sensitivity or shifts in their response criterion.

PMID- 29566791
TI  - NIH/Kennedy Center Workshop on Music and the Brain: Finding Harmony.
AB  - The National Institutes of Health and John F. Kennedy Center for the Performing
      Arts convened a panel of experts to discuss the current state of research on
      music and the brain. The panel generated research recommendations to accelerate
      the study of music's effects on the brain and the implications for human health.

PMID- 29566792
TI  - An Integrative Framework for Sensory, Motor, and Cognitive Functions of the
      Posterior Parietal Cortex.
AB  - Throughout the history of modern neuroscience, the parietal cortex has been
      associated with a wide array of sensory, motor, and cognitive functions. The use
      of non-human primates as a model organism has been instrumental in our current
      understanding of how areas in the posterior parietal cortex (PPC) modulate our
      perception and influence our behavior. In this Perspective, we highlight a series
      of influential studies over the last five decades examining the role of the PPC
      in visual perception and motor planning. We also integrate long-standing views of
      PPC functions with more recent evidence to propose a more general model framework
      to explain integrative sensory, motor, and cognitive functions of the PPC.

PMID- 29566795
TI  - Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3
      R451C Knockin Mice.

PMID- 29566796
TI  - Cerebral Embolic Risk During Transcatheter Mitral Valve Interventions: An
      Unaddressed and Unmet Clinical Need?
AB  - As new transcatheter mitral valve (MV) interventions continuously evolve,
      potential procedure-related adverse events demand careful investigation. The risk
      of cerebral embolic damage is ubiquitous in any left-sided structural heart
      intervention (and potentially linked to long-term neurocognitive sequelae);
      therefore, efforts to evaluate these aspects in the field of catheter-based MV
      procedures are justified. Given the peculiarities of MV anatomy, MV disease, and
      MV procedures, the lessons learned from other transcatheter heart interventions
      (i.e., transcatheter aortic valve replacement) cannot be directly translated to
      MV applications. Through a systematic assessment of available evidence, the
      authors present and discuss procedure- and patient-related factors potentially
      associated with cerebral embolic risk during catheter-based MV interventions.
      Given the paucity of available data in this field, future large, dedicated
      studies are needed to understand whether cerebral embolic injury represents a
      real clinical issue during MV procedures.

PMID- 29566798
TI  - What Is the IMPACT of Practice Variation in Congenital Interventional Cardiology?

PMID- 29566794
TI  - Tau Kinetics in Neurons and the Human Central Nervous System.
AB  - We developed stable isotope labeling and mass spectrometry approaches to measure
      the kinetics of multiple isoforms and fragments of tau in the human central
      nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived
      neurons. Newly synthesized tau is truncated and released from human neurons in 3
      days. Although most tau proteins have similar turnover, 4R tau isoforms and
      phosphorylated forms of tau exhibit faster turnover rates, suggesting unique
      processing of these forms that may have independent biological activities. The
      half-life of tau in control human iPSC-derived neurons is 6.74 +/- 0.45 days and
      in human CNS is 23 +/- 6.4 days. In cognitively normal and Alzheimer's disease
      participants, the production rate of tau positively correlates with the amount of
      amyloid plaques, indicating a biological link between amyloid plaques and tau
      physiology.

PMID- 29566797
TI  - Variations in Practice Patterns and Consistency With Published Guidelines for
      Balloon Aortic and Pulmonary Valvuloplasty: An Analysis of Data From the IMPACT
      Registry.
AB  - OBJECTIVES: The authors sought to study variation in the practice of balloon
      aortic (BAV) and pulmonary valvuloplasty (BPV). BACKGROUND: The IMPACT (IMProving
      Adult and Congenital Treatment) registry provides an opportunity to study
      practice variation in transcatheter interventions for congenital heart disease.
      METHODS: The authors studied BAV and BPV in the IMPACT registry from January 1,
      2011, to September 30, 2015, using hierarchical multivariable models to measure
      hospital-level variation in: 1) the distribution of indications for intervention;
      and 2) in cases with "high resting gradient" as the indication, consistency with
      published guidelines. RESULTS: A total of 1,071 BAV cases at 60 hospitals and
      2,207 BPV cases at 75 hospitals were included. The indication for BAV was high
      resting gradient in 82%, abnormal stress test or electrocardiogram (2%), left
      ventricular dysfunction (11%), and symptoms (5%). Indications for BPV were high
      resting gradient in 82%, right-left shunt (6%), right ventricular dysfunction
      (7%), and symptoms (5%). No association between hospital characteristics and
      distribution of indications was demonstrated. Among interventions performed for
      "high resting gradient," there was significant adjusted hospital-level variation
      in the rates of cases performed consistently with guidelines. For BAV,
      significant differences were seen across census regions, with hospitals in the
      East and South more likely to practice consistently than those in the Midwest and
      West (p = 0.005). For BPV, no association was found between hospital factors and
      rates of consistent practice, but there was significant interhospital variation
      (median rate ratio: 1.4; 95% confidence interval: 1.2 to 1.6; p < 0.001).
      CONCLUSIONS: There is measurable hospital-level variation in the practice of BAV
      and BPV. Further research is necessary to determine whether this affects outcomes
      or resource use.

PMID- 29566799
TI  - Branch Pulmonary Artery Valve Implantation Reduces Pulmonary Regurgitation and
      Improves Right Ventricular Size/Function in Patients With Large Right Ventricular
      Outflow Tracts.
AB  - OBJECTIVES: The authors sought to assess the intermediate-term effects of
      percutaneous placed valves in the branch pulmonary artery (PA) position.
      BACKGROUND: Most patients with large right ventricular outflow tracts (RVOTs) are
      excluded from available percutaneous pulmonary valve options. In some of these
      patients, percutaneous branch PA valve implantation may be feasible. The longer
      term effects of valves in the branch PA position is unknown. METHODS:
      Retrospective data were collected on patients with significant pulmonary
      regurgitation who had a percutaneous branch PA valve attempted. RESULTS:
      Percutaneous branch PA valve implantation was attempted in 34 patients (18
      bilateral and 16 unilateral). One-half of the patients were in New York Heart
      Association (NHYA) functional class III or IV pre-implantation. There were 2
      failed attempts and 6 procedural complications. At follow-up, only 1 patient had
      more than mild valvar regurgitation. The right ventricular end-diastolic volume
      index decreased from 147 (range: 103 to 478) ml/m2 to 101 (range: 76 to 429)
      ml/m2, p < 0.01 (n = 16), and the right ventricular end-systolic volume index
      decreased from 88.5 (range: 41 to 387) ml/m2 to 55.5 (range: 40.2 to 347) ml/m2,
      p < 0.01 (n = 13). There were 5 late deaths. At a median follow-up of 2 years,
      all other patients were in NYHA functional class I or II. CONCLUSIONS:
      Percutaneous branch PA valve implantation results in a reduction in right
      ventricular volume with clinical benefit in the intermediate term. Until
      percutaneous valve technology for large RVOTs is refined and more widely
      available, branch PA valve implantation remains an option for select patients.

PMID- 29566800
TI  - Branch Pulmonary Valves: Lessons Learned.

PMID- 29566801
TI  - Transcatheter Pulmonary Valve Replacement With the Melody Valve in Small Diameter
      Expandable Right Ventricular Outflow Tract Conduits.
AB  - OBJECTIVES: This study sought to evaluate the safety, feasibility, and outcomes
      of transcatheter pulmonary valve replacement (TPVR) in conduits <=16 mm in
      diameter. BACKGROUND: The Melody valve (Medtronic, Minneapolis, Minnesota) is
      approved for the treatment of dysfunctional right ventricular outflow tract
      (RVOT) conduits >=16 mm in diameter at the time of implant. Limited data are
      available regarding the use of this device in smaller conduits. METHODS: The
      study retrospectively evaluated patients from 9 centers who underwent
      percutaneous TPVR into a conduit that was <=16 mm in diameter at the time of
      implant, and reported procedural characteristics and outcomes. RESULTS: A total
      of 140 patients were included and 117 patients (78%; median age and weight 11
      years of age and 35 kg, respectively) underwent successful TPVR. The median
      original conduit diameter was 15 (range: 9 to 16) mm, and the median narrowest
      conduit diameter was 11 (range: 4 to 23) mm. Conduits were enlarged to a median
      diameter of 19 mm (29% larger than the implanted diameter), with no difference
      between conduits. There was significant hemodynamic improvement post-implant,
      with a residual peak RVOT pressure gradient of 7 mm Hg (p < 0.001) and no
      significant pulmonary regurgitation. During a median follow-up of 2.0 years,
      freedom from RVOT reintervention was 97% and 89% at 2 and 4 years, respectively,
      and there were no deaths and 5 cases of endocarditis (incidence rate 2.0% per
      patient-year). CONCLUSIONS: In this preliminary experience, TPVR with the Melody
      valve into expandable small diameter conduits was feasible and safe, with
      favorable early and long-term procedural and hemodynamic outcomes.

PMID- 29566802
TI  - Overstepping the Boundaries of Percutaneous Pulmonary Valve Placement Guidelines:
      Renegade or Renaissance?

PMID- 29566803
TI  - Conscious Sedation Versus General Anesthesia in Transcatheter Aortic Valve
      Replacement: The German Aortic Valve Registry.
AB  - OBJECTIVES: The aims of this study were to report on the use of local anesthesia
      or conscious sedation (LACS) and general anesthesia in transcatheter aortic valve
      replacement and to analyze the impact on outcome. BACKGROUND: Transcatheter
      aortic valve replacement can be performed in LACS or general anesthesia.
      Potential benefits of LACS, such as faster procedures and shorter hospital stays,
      need to be balanced with safety. METHODS: A total of 16,543 patients from the
      German Aortic Valve Registry from 2011 to 2014 were analyzed, and propensity
      matched analyses were performed to correct for potential selection bias. RESULTS:
      LACS was used in 49% of patients (8,121 of 16,543). In hospital, LACS was
      associated with lower rates of low-output syndrome, respiratory failure,
      delirium, cardiopulmonary resuscitation, and death. There was no difference in
      paravalvular leakage (II+) between LACS and general anesthesia in the entire
      population (5% vs. 4.8%; p = 0.76) or in the matched population (3.9% vs. 4.9%, p
      = 0.13). The risk for prolonged intensive care unit stay (>=3 days) was
      significantly reduced with LACS (odds ratio: 0.82; 95% confidence interval [CI]:
      0.73 to 0.92; p = 0.001). Thirty-day mortality was lower with LACS in the entire
      population (3.5% vs. 4.9%; hazard ratio [HR]: 0.72; 95% CI: 0.60 to 0.86; p <
      0.001) and in the matched population (2.8% vs. 4.6%; HR: 0.6; 95% CI: 0.45 to
      0.8; p < 0.001). However, no differences in 1-year mortality between both groups
      in the entire population (16.5% vs. 16.9%; HR: 0.93; 95% CI: 0.85 to 1.02; p =
      0.140) and in the propensity-matched population (14.1% vs. 15.5%; HR: 0.90; 95%
      CI: 0.78 to 1.03; p = 0.130) were observed. CONCLUSIONS: Use of LACS in
      transcatheter aortic valve replacement is safe, with fewer post-procedural
      complications and lower early mortality, suggesting its broad application.

PMID- 29566804
TI  - Local Anesthesia-Conscious Sedation: The Contemporary Gold Standard for
      Transcatheter Aortic Valve Replacement.

PMID- 29566806
TI  - Transcatheter Aortic Valve Replacement Risk Prediction for Benchmarking: Work
      Under Construction.

PMID- 29566805
TI  - Inclusion of Functional Status Measures in the Risk Adjustment of 30-Day
      Mortality After Transcatheter Aortic Valve Replacement: A Report From the Society
      of Thoracic Surgeons/American College of Cardiology TVT Registry.
AB  - OBJECTIVES: The aim of this study was to develop and validate a risk adjustment
      model for 30-day mortality after transcatheter aortic valve replacement (TAVR)
      that accounted for both standard clinical factors and pre-procedural health
      status and frailty. BACKGROUND: Assessment of risk for TAVR is important both for
      patient selection and provider comparisons. Prior efforts for risk adjustment
      have focused on in-hospital mortality, which is easily obtainable but can be
      biased because of early discharge of ill patients. METHODS: Using data from
      patients who underwent TAVR as part of the Society of Thoracic Surgeons/American
      College of Cardiology TVT (Transcatheter Valve Therapy) Registry (June 2013 to
      May 2016), a hierarchical logistic regression model to estimate risk for 30-day
      mortality after TAVR based only on pre-procedural factors and access site was
      developed and internally validated. The model included factors from the original
      TVT Registry in-hospital mortality model but added the Kansas City Cardiomyopathy
      Questionnaire (health status) and gait speed (5-m walk test). RESULTS: Among
      21,661 TAVR patients at 188 sites, 1,025 (4.7%) died within 30 days. Independent
      predictors of 30-day death included older age, low body weight, worse renal
      function, peripheral artery disease, home oxygen, prior myocardial infarction,
      left main coronary artery disease, tricuspid regurgitation, nonfemoral access,
      worse baseline health status, and inability to walk. The predicted 30-day
      mortality risk ranged from 1.1% (lowest decile of risk) to 13.8% (highest decile
      of risk). The model was able to stratify risk on the basis of patient factors
      with good discrimination (C = 0.71 [derivation], C = 0.70 [split-sample
      validation]) and excellent calibration, both overall and in key patient
      subgroups. CONCLUSIONS: A clinical risk model was developed for 30-day death
      after TAVR that included clinical data as well as health status and frailty. This
      model will facilitate tracking outcomes over time as TAVR expands to lower risk
      patients and to less experienced sites and will allow an objective comparison of
      short-term mortality rates across centers.

PMID- 29566807
TI  - Staged Endovascular Intervention of Bilateral Pulmonary Artery Stenosis.

PMID- 29566808
TI  - The Kaltenbach Bonzel Bare Wire: Not the Full Story.

PMID- 29566809
TI  - Costs of Transcatheter Aortic Valve Replacement: Implications of Proposed
      Medicare Cuts.

PMID- 29566810
TI  - State-of-the-Art Papers: Gemstones.

PMID- 29566811
TI  - A note from the Editor's desk.

PMID- 29566813
TI  - Low-Flow, Low-Gradient Aortic Stenosis: TAVR In, Dobutamine Stress
      Echocardiography Out?

PMID- 29566812
TI  - Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient
      Aortic Stenosis: The TOPAS-TAVI Registry.
AB  - BACKGROUND: Few data exist on patients with low-flow, low-gradient aortic
      stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR).
      Also, very scarce data exist on the usefulness of dobutamine stress
      echocardiography (DSE) before TAVR in these patients. OBJECTIVES: The authors
      sought to evaluate clinical outcomes and changes in left ventricular ejection
      fraction (LVEF) following TAVR in patients with classical LFLG-AS. METHODS: This
      multicenter registry included 287 patients with LFLG-AS undergoing TAVR. DSE was
      performed before TAVR in 234 patients and the presence of contractile reserve was
      defined as an increase of >=20% in stroke volume. Transthoracic echocardiography
      was repeated at hospital discharge and at 1-year follow-up. Clinical follow-up
      was obtained at 1 and 12 months, and yearly thereafter. RESULTS: The median
      Society of Thoracic Surgeons score of the study population was 7.7%
      (interquartile range 5.3% to 12.0%), and the mean LVEF and transvalvular gradient
      were 30.1 +/- 9.7% and 25.4 +/- 6.6 mm Hg, respectively. The presence of
      contractile reserve was observed in 45% of patients at DSE. Mortality rates were
      3.8%, 20.1%, and 32.3% at 30 days, 1 year, and 2 years, respectively. On
      multivariable analysis, chronic obstructive pulmonary disease (p = 0.022) and
      lower hemoglobin values (p < 0.001) were associated with all-cause mortality.
      Lower hemoglobin values (p = 0.004) and moderate-to-severe aortic regurgitation
      post-TAVR (p = 0.018) were predictors of the composite of mortality and
      rehospitalization due to heart failure. LVEF increased by 8.3% (95% confidence
      interval: 6% to 11%) at 1-year follow-up, and the lack of prior coronary artery
      bypass graft (p = 0.004), a lower LVEF at baseline (p < 0.001), and a lower
      stroke volume index at baseline (p = 0.019) were associated with greater increase
      in LVEF. The absence of contractile reserve at baseline DSE was not associated
      with any negative effect on clinical outcomes or LVEF changes at follow-up.
      CONCLUSIONS: TAVR was associated with good periprocedural outcomes in patients
      with LFLG-AS. However, approximately one-third of LFLG-AS TAVR recipients died at
      2-year follow-up, with pulmonary disease, anemia, and residual paravalvular leaks
      associated with poorer outcomes. LVEF improved following TAVR, but DSE failed to
      predict clinical outcomes or LVEF changes over time. (Multicenter Prospective
      Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS Study]; NCT01835028).

PMID- 29566814
TI  - Reduced Left Ventricular Ejection Fraction in Patients With Aortic Stenosis.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is reduced in a subset of
      patients with severe aortic stenosis (AS). OBJECTIVES: The authors sought to
      determine the temporal course of reduced LVEF, its predictors, and its impact on
      prognosis in severe AS. METHODS: Serial echocardiograms of 928 consecutive
      patients with first-time diagnosis of severe AS (aortic valve area [AVA] <=1 cm2)
      who had at least 1 echocardiogram before the diagnosis were evaluated. A total of
      3,684 echocardiograms (median 3 studies per patient) within the preceding 10
      years were analyzed. RESULTS: At the initial diagnosis, 196 (21%) patients had an
      LVEF <50% (35.1 +/- 9.7%) and 732 (79%) had an LVEF >=50% (64.2 +/- 6.1%). LVEF
      deterioration had begun before AS became severe for those with an LVEF <50% and
      accelerated after AVA reached 1.2 cm2, whereas mean LVEF remained >60% in
      patients with LVEF >=50% at initial diagnosis. The strongest predictor for LVEF
      deterioration was LVEF <60% at 3 years before AS became severe (odds ratio: 0.86;
      95% confidence interval: 0.83 to 0.89; p < 0.001). During the median follow-up of
      3.3 years, mortality was significantly worse, not only for patients with an LVEF
      <50%, but for patients with an LVEF of 50% <= LVEF <60% compared with patients
      with an LVEF >=60% even after aortic valve replacement (p < 0.001). CONCLUSIONS:
      In patients with severe AS and reduced LVEF, a decline in LVEF began before AS
      became severe and accelerated after AVA reached 1.2 cm2. LVEF <60% in the
      presence of moderate AS predicts further deterioration of LVEF and appears to
      represent abnormal LVEF in AS.

PMID- 29566815
TI  - Where Do Low-Gradient, Low-EF AS Patients Come From?: Maybe They're Born That
      Way.

PMID- 29566793
TI  - Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.
AB  - To identify novel genes associated with ALS, we undertook two lines of
      investigation. We carried out a genome-wide association study comparing 20,806
      ALS cases and 59,804 controls. Independently, we performed a rare variant burden
      analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through
      both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene
      associated with ALS. Interestingly, mutations predominantly in the N-terminal
      motor domain of KIF5A are causative for two neurodegenerative diseases:
      hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In
      contrast, ALS-associated mutations are primarily located at the C-terminal cargo
      binding tail domain and patients harboring loss-of-function mutations displayed
      an extended survival relative to typical ALS cases. Taken together, these results
      broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen
      the role of cytoskeletal defects in the pathogenesis of ALS.

PMID- 29566817
TI  - Cardiac Resynchronization Therapy in the Absence of LV Mechanical Dyssynchrony:
      Primum Non Nocere.

PMID- 29566816
TI  - Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS
      Complexes.
AB  - BACKGROUND: Cross correlation analysis (CCA) using tissue Doppler imaging has
      been shown to be associated with outcome after cardiac resynchronization therapy
      (CRT) in patients with heart failure (HF) with wide QRS. However, its
      significance in patients with narrow QRS treated with CRT is unknown. OBJECTIVES:
      The aim of the current study was to investigate the association of mechanical
      activation delay by CCA with study outcome in patients with HF enrolled in the
      EchoCRT trial. METHODS: Baseline CCA could be performed from tissue Doppler
      imaging in the apical views in 807 of 809 (99.7%) enrolled patients, and 6-month
      follow-up could be performed in 610 of 635 (96%) patients with available
      echocardiograms. Patients with a pre-specified maximal activation delay >=35 ms
      were considered to have significant delay. The study outcome was HF
      hospitalization or death. RESULTS: Of 807 patients, 375 (46%) did not have
      delayed mechanical activation at baseline by CCA. Patients without delayed
      mechanical activation who were randomized to CRT-On compared with CRT-Off had an
      increased risk of poor outcome (hazard ratio: 1.70; 95% confidence interval: 1.13
      to 2.55; p = 0.01) with a significant interaction term (p = 0.04) between delayed
      mechanical activation and device randomization for the endpoint. Among patients
      with paired baseline and follow-up data with no events before 6-month follow-up
      (n = 541), new-onset delayed mechanical activation in the CRT-On group showed a
      significant increase in unfavorable events (hazard ratio: 3.73; 95% confidence
      interval: 1.15 to 12.14; p = 0.03). CONCLUSIONS: In the EchoCRT population,
      absence of delayed mechanical activation by CCA was significantly associated with
      poor outcomes, possibly due to the onset of new delayed mechanical activation
      with CRT pacing. (Echocardiography Guided Cardiac Resynchronization Therapy
      [EchoCRT] Trial; NCT00683696).

PMID- 29566818
TI  - Improved Survival After the Ross Procedure Compared With Mechanical Aortic Valve
      Replacement.
AB  - BACKGROUND: It is unclear whether the Ross procedure offers superior survival
      compared with mechanical aortic valve replacement (AVR). OBJECTIVES: This study
      evaluated experience and compared long-term survival between the Ross procedure
      and mechanical AVR. METHODS: Between 1992 and 2016, a total of 392 Ross
      procedures were performed. These were compared with 1,928 isolated mechanical
      AVRs performed during the same time period as identified using the University of
      Melbourne and Australia and New Zealand Society of Cardiac and Thoracic Surgeons'
      Cardiac Surgery Databases. Only patients between 18 and 65 years of age were
      included. Propensity-score matching was performed for risk adjustment. RESULTS:
      Ross procedure patients were younger, and had fewer cardiovascular risk factors.
      The Ross procedure was associated with longer cardiopulmonary bypass and aortic
      cross-clamp times. Thirty-day mortality was similar (Ross, 0.3%; mechanical,
      0.8%; p = 0.5). Ross procedure patients experienced superior unadjusted long-term
      survival at 20 years (Ross, 95%; mechanical, 68%; p < 0.001). Multivariable
      analysis showed the Ross procedure to be associated with a reduced risk of late
      mortality (hazard ratio: 0.34; 95% confidence internal: 0.17 to 0.67; p < 0.001).
      Among 275 propensity-score matched pairs, Ross procedure patients had superior
      survival at 20 years (Ross, 94%; mechanical, 84%; p = 0.018). CONCLUSIONS: In
      this Australian, propensity-score matched study, the Ross procedure was
      associated with better long-term survival compared with mechanical AVR. In
      younger patients, with a long life expectancy, the Ross procedure should be
      considered in centers with sufficient expertise.

PMID- 29566819
TI  - Is it Time to Reconsider Use of the Ross Procedure for Adults?

PMID- 29566820
TI  - Physiological Stress Elicits Impaired Left Ventricular Function in Preterm-Born
      Adults.
AB  - BACKGROUND: Experimental and clinical studies show that prematurity leads to
      altered left ventricular (LV) structure and function with preserved resting LV
      ejection fraction (EF). Large-scale epidemiological data now links prematurity to
      increased early heart failure risk. OBJECTIVES: The authors performed
      echocardiographic imaging at prescribed exercise intensities to determine whether
      preterm-born adults have impaired LV functional response to physical exercise.
      METHODS: We recruited 101 normotensive young adults born preterm (n = 47; mean
      gestational age 32.8 +/- 3.2 weeks) and term (n = 54) for detailed cardiovascular
      phenotyping. Full clinical resting and exercise stress echocardiograms were
      performed, with apical 4-chamber views collected while exercising at 40%, 60%,
      and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise
      testing. RESULTS: Preterm-born individuals had greater LV mass (p = 0.015) with
      lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born
      control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was
      6.7% lower in preterm subjects (71.9 +/- 8.7% vs 78.6 +/- 5.4%; p = 0.004) and
      further declined to 7.3% below the term-born group at 80% exercise intensity
      (69.8 +/- 6.4% vs 77.1 +/- 6.3%; p = 0.004). Submaximal cardiac output reserve
      was 56% lower in preterm-born subjects versus term-born control subjects at 40%
      of peak exercise capacity (729 +/- 1,162 ml/min/m2 vs. 1,669 +/- 937 ml/min/m2; p
      = 0.021). LV length and resting peak systolic longitudinal strain predicted EF
      increase from rest to 60% exercise intensity in the preterm group (r = 0.68, p =
      0.009 and r = 0.56, p = 0.031, respectively). CONCLUSIONS: Preterm-born young
      adults had impaired LV response to physiological stress when subjected to
      physical exercise, which suggested a reduced myocardial functional reserve that
      might help explain their increased risk of early heart failure. (Young Adult
      Cardiovascular Health sTudy [YACHT]; NCT02103231).

PMID- 29566821
TI  - Cardiovascular Stress Test in People Born Preterm: A Peephole Into the Future.

PMID- 29566822
TI  - Coronary Angiography and Percutaneous Coronary Intervention After Transcatheter
      Aortic Valve Replacement.
AB  - Transcatheter aortic valve replacement (TAVR) has revolutionized the management
      of patients with symptomatic severe aortic stenosis, and indications are
      expanding towards treating younger patients with lower-risk profiles. Given the
      progressive nature of coronary artery disease and its high prevalence in those
      with severe aortic stenosis, coronary angiography and percutaneous coronary
      intervention will become increasingly necessary in patients after TAVR. There are
      some data suggesting that there are technical difficulties with coronary re
      engagement, particularly in patients with self-expanding valves that, by design,
      extend above the coronary ostia. The authors review the challenges of coronary
      angiography and percutaneous coronary intervention post-TAVR and examine the
      geometric interactions between currently approved transcatheter aortic valves and
      coronary ostia, while providing a practical guide on how to manage these
      potentially complex situations.

PMID- 29566823
TI  - Palliative Care Education in Cardiology.

PMID- 29566824
TI  - Rivaroxaban With and Without Amiodarone in Renal Impairment.

PMID- 29566825
TI  - Reply: Value of Serial ST2 Measurements in Acute Heart Failure: miRNA Regulation
      and Genetic Factors.

PMID- 29566826
TI  - Value of Serial ST2 Measurements in Acute Heart Failure: miRNA Regulation and
      Genetic Factors.

PMID- 29566827
TI  - Abdominal Obesity as a Risk Predictor: Closer Than Body Mass Index But Not Close
      Enough.

PMID- 29566828
TI  - Reply: Abdominal Obesity as a Risk Predictor: Closer Than Body Mass Index But Not
      Close Enough.

PMID- 29566829
TI  - Affordability of New Technologies: The Next Frontier.

PMID- 29566830
TI  - Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases,
      and Cures.
AB  - OBJECTIVES: To analyze how value-based pricing (VBP), which grounds the price
      paid for pharmaceuticals in their value, can manage "affordability" challenges,
      defined as drugs that meet cost-effectiveness thresholds but are "unaffordable"
      within the short-run budget. METHODS: Three specific contexts are examined,
      drawing on recent experience. First, an effective new treatment for a chronic,
      progressive disease, such as hepatitis C, creates a budget spike that is
      transitory because initial prevalence is high, relative to current incidence.
      Second, "cures" that potentially provide lifetime benefits may claim abnormally
      high VBP prices, with high immediate budget impact potentially/partially offset
      by deferred cost savings. Third, although orphan drugs in principle target rare
      diseases, in aggregate they pose affordability concerns because of the growing
      number of orphan indications and increasingly high prices. RESULTS: For mass
      diseases, the transitory budget impact of treating the accumulated patient stock
      can be managed by stratified rollout that delays treatment of stable patients and
      prioritizes patients at high risk of deterioration. Delay spreads the budget
      impact and permits potential savings from launch of competing treatments. For
      cures, installment payments contingent on outcomes could align payment flows and
      appropriately shift risk to producers. This approach, however, entails high
      administrative and incentive costs, especially if applied across multiple payers
      in the United States. For orphan drugs, the available evidence on research and
      development trends and returns argues against the need for a higher VBP threshold
      to incentivize research and development in orphan drugs, given existing statutory
      benefits under orphan drug legislation.

PMID- 29566831
TI  - The ICER Value Framework: Integrating Cost Effectiveness and Affordability in the
      Assessment of Health Care Value.
AB  - What should be the relationship between the concepts of cost effectiveness and
      affordability in value assessments for health care interventions? This question
      has received greater attention in recent years given increasing financial
      pressures on health systems, leading to different views on how assessment reports
      and decision-making processes can provide the best structure for considering both
      elements. In the United States, the advent of explicit value frameworks to guide
      drug assessments has also focused attention on this issue, driven in part by the
      prominent inclusion of affordability within the value framework used to guide
      reports from the Institute for Clinical and Economic Review. After providing a
      formal definition of affordability for health care systems, this article argues
      that, even after using empirical estimates of true health system opportunity
      cost, cost-effectiveness thresholds cannot by themselves be set in a way that
      subsumes questions about short-term affordability. The article then presents an
      analysis of different approaches to integrating cost effectiveness and budget
      impact assessments within information to guide decision making. The evolution and
      experience with the Institute for Clinical and Economic Review value framework
      are highlighted, providing lessons learned and guiding principles for future
      efforts to bring measures of affordability within the scope of value assessment.

PMID- 29566832
TI  - Resolving the "Cost-Effective but Unaffordable" Paradox: Estimating the Health
      Opportunity Costs of Nonmarginal Budget Impacts.
AB  - Considering whether or not a proposed investment (an intervention, technology, or
      program of care) is affordable is really asking whether the benefits it offers
      are greater than its opportunity cost. To say that an investment is cost
      effective but not affordable must mean that the (implicit or explicit)
      "threshold" used to judge cost-effectiveness does not reflect the scale and value
      of the opportunity costs. Existing empirical estimates of health opportunity
      costs are based on cross-sectional variation in expenditure and mortality
      outcomes by program budget categories (PBCs) and do not reflect the likely effect
      of nonmarginal budget impacts on health opportunity costs. The UK Department of
      Health regularly updates the needs-based target allocation of resources to local
      areas of the National Health Service (NHS), creating two subgroups of local areas
      (those under target allocation and those over). These data provide the
      opportunity to explore how the effects of changes in health care expenditure
      differ with available resources. We use 2008-2009 data to evaluate two
      econometric approaches to estimation and explore a range of criteria for
      accepting subgroup specific effects for differences in expenditure and outcome
      elasticities across the 23 PBCs. Our results indicate that health opportunity
      costs arising from an investment imposing net increases in expenditure are
      underestimated unless account is taken of likely nonmarginal effects. They also
      indicate the benefits (reduced health opportunity costs or increased value-based
      price of a technology) of being able to "smooth" these nonmarginal budget impacts
      by health care systems borrowing against future budgets or from manufacturers
      offering "mortgage" type arrangements.

PMID- 29566833
TI  - Paying for Cures: Perspectives on Solutions to the "Affordability Issue".
AB  - Curative therapies and other medicines considered "game-changing" in terms of
      health gain can be accompanied by high demand and high list prices that pose
      budget challenges to public and private payers and health systems-the so-called
      affordability issue. These challenges are exacerbated when longer term
      effectiveness, and thus value for money, is uncertain, but they can arise even
      when treatments are proven to be highly cost-effective at the time of launch.
      This commentary reviews innovative payment solutions proposed in the literature
      to address the affordability issue, including the use of credit markets and of
      staged payments linked to patient outcomes, and draws on discussions with payers
      in the United States and Europe on the feasibility or desirability of
      operationalizing any of the alternative financing and payment strategies that
      appear in the literature. This included a small number of semistructured
      interviews. We conclude that there is a mismatch between the enthusiasm in the
      academic literature for developing new approaches and the scepticism of payers
      that they can work or are necessary. For the foreseeable future, affordability
      pressures will continue to be handled by aggressive price bargaining, high co
      pays (in systems in which this is possible), and restricting access to subgroups
      of patients. Of the mechanisms we explored, outcomes-based payments were of most
      interest to payers, but the costs associated with operating such schemes,
      together with implementation challenges, did not make them an attractive option
      for managing affordability.

PMID- 29566834
TI  - Affordability of Health Care: A Global Crisis.

PMID- 29566835
TI  - Estimating the Learning Curve of a Novel Medical Device: Bipolar Sealer Use in
      Unilateral Total Knee Arthroplasties.
AB  - BACKGROUND: The use of cost-effectiveness analysis for medical devices has proven
      to be challenging because of the existence of the learning effects in the device
      operator interactions. The need for the relevant analytical framework for
      assessing the economic value of such technologies has been recognized.
      OBJECTIVES: To present a modified difference-in-differences (DID) cost
      effectiveness methodology that facilitates visualization of a new health
      technology's learning curve. METHODS: Using the Premier Perspective database
      (Premier Inc., Charlotte, NC), we examined the impact of physicians adopting a
      bipolar sealer (BPS) to control blood loss in primary unilateral total knee
      arthroplasties on hospital lengths of stay and total hospitalization costs when
      compared with two control groups. In our DID approach, we substituted month-from
      adoption for the calendar-month-of-adoption in both graphical representations and
      ordinary least-squares regression results to estimate the effect of the BPS.
      RESULTS: The results clearly demonstrated a learning curve associated with the
      adoption of the BPS technology. Although the reductions in length of stay were
      immediate, the first postadoption year costs increased by $1335 (extrahospital
      controls) to $1565 (within-hospital controls). Importantly, and also consistent
      with a learning curve hypothesis, these initial higher costs were offset by
      subsequent cost savings in the second and third years postadoption. CONCLUSIONS:
      The presented modified DID approach is a suitable and versatile analytical tool
      for economic evaluation of a slowly diffusing medical device or health
      technology. It provides a better understanding of the potential learning effects
      associated with relevant interventions.

PMID- 29566836
TI  - Resource Use and Cost of Alzheimer's Disease in France: 18-Month Results from the
      GERAS Observational Study.
AB  - BACKGROUND: There is little longitudinal data on resource use and costs
      associated with Alzheimer's disease (AD) in France. OBJECTIVES: To evaluate
      resource use and societal costs associated with AD in a French cohort of patients
      and their caregivers and the effect of patient cognitive decline on costs over an
      18-month period. METHODS: Community-dwelling patients with mild, moderate, or
      moderately severe/severe AD dementia (n = 419) were followed-up for 18 months.
      Total societal costs were estimated by applying 2010 unit costs to resource use,
      including outpatient visits, hospital days, institutionalization, and caregiver
      hours. Cognitive function was assessed by Mini-Mental State Examination scores.
      RESULTS: Mean cumulative total costs over the 18-month period were ?24,140 for
      patients with mild AD dementia, ?34,287 for those with moderate AD dementia, and
      ?44,171 for those with moderately severe/severe AD dementia (P < 0.001; ANOVA
      comparison between severity groups). The biggest contributor to total societal
      costs was caregiver informal care (>50% of total costs at all stages of AD
      dementia). Cognitive decline (>=3-point decrease in Mini-Mental State Examination
      score or institutionalization) was associated with a 12.5% increase in total
      costs (P = 0.02). Significant differences were observed across severity groups
      for caregiver time (P < 0.001); mean monthly caregiver time increased at each
      time point over the 18 months in each severity group. CONCLUSIONS: Increasing
      severity of AD dementia in France is associated with increased use of resources
      as well as increased total societal and patient costs; informal care was the
      greatest cost contributor. Clinically meaningful cognitive decline is associated
      with significantly increased costs.

PMID- 29566837
TI  - Economic Evaluation of Treating Skeletal-Related Events among Prostate Cancer
      Patients.
AB  - OBJECTIVES: To evaluate the economic burden of treating skeletal-related events
      (SREs) in prostate cancer (PC) patients with bone metastasis from an insurer
      perspective. METHODS: We conducted a retrospective cohort analysis using claims
      data. PC patients with bone metastasis were identified in the MarketScan
      Databases between January 1, 2004, and March 1, 2014. The propensity score
      matching approach was used to match patients with SREs to those without SREs. A
      pseudo-SRE date was assigned to the control group. We compared 6-month and 12
      month total costs of patients between two groups after the SRE or pseudo-SRE
      date. All costs were adjusted to 2014 US$. RESULTS: We identified 4083 PC men
      with bone metastasis, from which 787 patients with SREs were matched (1:1) to
      those without SREs. On average, the total 6-month cost of treating patients with
      SREs was $43,746 compared with $25,956 in the matched control cohort (P < 0.05).
      The largest proportion of differences in costs between the two groups was
      incurred in the first month after the SRE index date or the pseudo-SRE date
      ($14,979 vs. $4,849; P < 0.05) and was mostly attributable to outpatient visits
      (43.4%; P < 0.05) and inpatient hospitalization (33.1%; P < 0.05). The total cost
      per patient over the 12-month period was $22,171 higher among patients with SREs
      than among patients without SREs (P < 0.05). CONCLUSIONS: Our findings suggest
      that SREs impose considerable burden on health resource utilization for payers.
      Costs attributable to SREs were substantial. Most costs were incurred in the
      first month after the occurrence of SREs. Although costs decreased thereafter,
      they remained significantly higher for patients with SREs in subsequent months
      compared with patients without SREs.

PMID- 29566838
TI  - Cost-Effectiveness of Antibiotic Prophylaxis Strategies for Transrectal Prostate
      Biopsy in an Era of Increasing Antimicrobial Resistance.
AB  - OBJECTIVES: To determine the optimal antibiotic prophylaxis strategy for
      transrectal prostate biopsy (TRPB) as a function of the local antibiotic
      resistance profile. METHODS: We developed a decision-analytic model to assess the
      cost-effectiveness of four antibiotic prophylaxis strategies: ciprofloxacin
      alone, ceftriaxone alone, ciprofloxacin and ceftriaxone in combination, and
      directed prophylaxis selection based on susceptibility testing. We used a payer's
      perspective and estimated the health care costs and quality-adjusted life-years
      (QALYs) associated with each strategy for a cohort of 66-year-old men undergoing
      TRPB. Costs and benefits were discounted at 3% annually. Base-case resistance
      prevalence was 29% to ciprofloxacin and 7% to ceftriaxone, reflecting
      susceptibility patterns observed at the Minneapolis Veterans Affairs Health Care
      System. Resistance levels were varied in sensitivity analysis. RESULTS: In the
      base case, single-agent prophylaxis strategies were dominated. Directed
      prophylaxis strategy was the optimal strategy at a willingness-to-pay threshold
      of $50,000/QALY gained. Relative to the directed prophylaxis strategy, the
      incremental cost-effectiveness ratio of the combination strategy was
      $123,333/QALY gained over the lifetime time horizon. In sensitivity analysis,
      single-agent prophylaxis strategies were preferred only at extreme levels of
      resistance. CONCLUSIONS: Directed or combination prophylaxis strategies were
      optimal for a wide range of resistance levels. Facilities using single-agent
      antibiotic prophylaxis strategies before TRPB should re-evaluate their strategies
      unless extremely low levels of antimicrobial resistance are documented.

PMID- 29566839
TI  - Cost-Effectiveness of First-Line Sevelamer and Lanthanum versus Calcium-Based
      Binders for Hyperphosphatemia of Chronic Kidney Disease.
AB  - BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients
      with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation
      comparing calcium-free binders sevelamer and lanthanum with calcium-based binders
      for patients with CKD. METHODS: Effectiveness data were obtained from a recent
      meta-analysis of randomized trials. Effectiveness was measured as life-years
      gained and translated to quality-adjusted life-years (QALYs) using utility
      weights from the literature. A Markov model consisting of non-dialysis-dependent
      (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the
      incremental costs and effects of sevelamer and lanthanum versus those of calcium
      based binders. A lifetime horizon was used and both costs and effects were
      discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the
      Canadian public payer perspective. Results of probabilistic sensitivity analysis
      were presented using cost-effectiveness acceptability curves. Sensitivity
      analyses were conducted for risk pooling methods, omission of dialysis costs, and
      persistence of drug effects on mortality. RESULTS: Sevelamer resulted in an
      incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and
      $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost
      effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort
      ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were
      included. CONCLUSIONS: Existing evidence does not clearly support the cost
      effectiveness of non-calcium-containing phosphate binders (sevelamer and
      lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients.
      Our study suggests that sevelamer may be cost-effective before dialysis onset.
      Because of the remaining uncertainty in several clinically relevant outcomes over
      time in DD-CKD and NDD-CKD patients, further research is encouraged.

PMID- 29566840
TI  - Real-World Evidence: Useful in the Real World of US Payer Decision Making? How?
      When? And What Studies?
AB  - OBJECTIVES: To examine how real-world evidence (RWE) is currently perceived and
      used in managed care environments, especially to inform pharmacy and therapeutic
      (P&T) committee decisions, to assess which study factors (e.g., data, design, and
      funding source) contribute to RWE utility in decisions, and to identify barriers
      to consideration of RWE studies in P&T decision making. METHODS: We conducted
      focus groups/telephone-based interviews and surveys to understand perceptions of
      RWE and assess awareness, quality, and relevance of two high-profile examples of
      published RWE studies. A purposive sample comprised 4 physicians, 15 pharmacists,
      and 1 researcher representing 18 US health plans and health system organizations.
      RESULTS: Participants reported that RWE was generally used, or useful, to inform
      safety monitoring, utilization management, and cost analysis, but less so to
      guide P&T decisions. Participants were not aware of the two sample RWE studies
      but considered both studies to be valuable. Relevant research questions and
      outcomes, transparent methods, study quality, and timely results contribute to
      the utility of published RWE. Perceived organizational barriers to the use of
      published RWE included lack of skill, training, and timely study results.
      CONCLUSIONS: Payers recognize the value of RWE, but use of such studies to inform
      P&T decisions varies from organization to organization and is limited. Relevance
      to payers, timeliness, and transparent methods were key concerns with RWE.
      Participants recognized the need for continuing education on evaluating and using
      RWE to better understand the study methods, findings, and applicability to their
      organizations.

PMID- 29566841
TI  - Sensitivity of Claims-Based Algorithms to Ascertain Smoking Status More Than
      Doubled with Meaningful Use.
AB  - BACKGROUND: The "meaningful use of certified electronic health record" policy
      requires eligible professionals to record smoking status for more than 50% of all
      individuals aged 13 years or older in 2011 to 2012. OBJECTIVES: To explore
      whether the coding to document smoking behavior has increased over time and to
      assess the accuracy of smoking-related diagnosis and procedure codes in
      identifying previous and current smokers. METHODS: We conducted an observational
      study with 5,423,880 enrollees from the year 2009 to 2014 in the Truven Health
      Analytics database. Temporal trends of smoking coding, sensitivity, specificity,
      positive predictive value, and negative predictive value were measured. RESULTS:
      The rate of coding of smoking behavior improved significantly by the end of the
      study period. The proportion of patients in the claims data recorded as current
      smokers increased 2.3-fold and the proportion of patients recorded as previous
      smokers increased 4-fold during the 6-year period. The sensitivity of each
      International Classification of Diseases, Ninth Revision, Clinical Modification
      code was generally less than 10%. The diagnosis code of tobacco use disorder
      (305.1X) was the most sensitive code (9.3%) for identifying smokers. The
      specificities of these codes and the Current Procedural Terminology codes were
      all more than 98%. CONCLUSIONS: A large improvement in the coding of current and
      previous smoking behavior has occurred since the inception of the meaningful use
      policy. Nevertheless, the use of diagnosis and procedure codes to identify
      smoking behavior in administrative data is still unreliable. This suggests that
      quality improvements toward medical coding on smoking behavior are needed to
      enhance the capability of claims data for smoking-related outcomes research.

PMID- 29566842
TI  - What Is the Evidence from Past National Institute of Health and Care Excellence
      Single-Technology Appraisals Regarding Company Submissions with Base-Case
      Incremental Cost-Effectiveness Ratios of Less Than L10,000/QALY?
AB  - BACKGROUND: The National Institute for Health and Care Excellence has recently
      proposed that company submissions with a base-case incremental cost-effectiveness
      ratio (ICER) of less than L10,000/quality-adjusted life-year (QALY) might be
      eligible for a "fast-track" appraisal. OBJECTIVES: To explore outcomes relating
      to previously conducted single-technology appraisals (STAs) with base-case ICERs
      of less than L10,000/QALY. METHODS: All STAs with published guidance from 2009 to
      2016 were included; those with company base-case ICERs of less than L10,000/QALY
      were identified and analyzed. A secondary analysis was also conducted for those
      with a company base-case ICER of L10,000 to L15,000/QALY. Relevant data were
      extracted and presented in a narrative and in tables. RESULTS: In total, 15% (26
      of 171) of STAs included a company submission with a base-case ICER of less than
      L10,000/QALY. Of these, 73% (19 of 26) were given positive recommendations after
      the first Appraisal Committee (AC) meeting, whereas 27% (7 of 26) were initially
      given a Minded No before receiving a positive recommendation in the final
      appraisal determination, albeit with restricted recommendations for three
      technologies. Five STAs had company base-case ICERs of L10,000 to L15,000/QALY
      and all received a positive recommendation after the first AC meeting.
      CONCLUSIONS: Most previous STAs with a company base-case ICER of L10,000 or even
      L15,000/QALY received a positive recommendation after the first AC meeting, but a
      number of them proved more complicated and required detailed appraisal, which
      influenced the final recommendation. This finding might have implications for the
      proposed fast-track process of the National Institute for Health and Care
      Excellence.

PMID- 29566843
TI  - The Importance of Model Structure in the Cost-Effectiveness Analysis of Primary
      Care Interventions for the Management of Hypertension.
AB  - BACKGROUND: Management of hypertension can lead to significant reductions in
      blood pressure, thereby reducing the risk of cardiovascular disease. Modeling the
      course of cardiovascular disease is not without complications, and uncertainty
      surrounding the structure of a model will almost always arise once a choice of a
      model structure is defined. OBJECTIVES: To provide a practical illustration of
      the impact on the results of cost-effectiveness of changing or adapting model
      structures in a previously published cost-utility analysis of a primary care
      intervention for the management of hypertension Targets and Self-Management for
      the Control of Blood Pressure in Stroke and at Risk Groups (TASMIN-SR). METHODS:
      The case study assessed the structural uncertainty arising from model structure
      and from the exclusion of secondary events. Four alternative model structures
      were implemented. Long-term cost-effectiveness was estimated and the results
      compared with those from the TASMIN-SR model. RESULTS: The main cost
      effectiveness results obtained in the TASMIN-SR study did not change with the
      implementation of alternative model structures. Choice of model type was limited
      to a cohort Markov model, and because of the lack of epidemiological data, only
      model 4 captured structural uncertainty arising from the exclusion of secondary
      events in the case study model. CONCLUSIONS: The results of this study indicate
      that the main conclusions drawn from the TASMIN-SR model of cost-effectiveness
      were robust to changes in model structure and the inclusion of secondary events.
      Even though one of the models produced results that were different to those of
      TASMIN-SR, the fact that the main conclusions were identical suggests that a more
      parsimonious model may have sufficed.

PMID- 29566844
TI  - Associations of Smoking, Physical Inactivity, Heavy Drinking, and Obesity with
      Quality-Adjusted Life Expectancy among US Adults with Depression.
AB  - OBJECTIVES: To examine associations between four health behaviors (smoking,
      physical inactivity, heavy alcohol drinking, and obesity) and three health
      indices (health-related quality of life, life expectancy, and quality-adjusted
      life expectancy (QALE)) among US adults with depression. METHODS: Data were
      obtained from the 2006, 2008, and 2010 Behavioral Risk Factor Surveillance System
      data. The EuroQol five-dimensional questionnaire (EQ-5D) health preference scores
      were estimated on the basis of extrapolations from the Centers for Disease
      Control and Prevention's healthy days measures. Depression scores were estimated
      using the eight-item Patient Health Questionnaire. Life expectancy estimates were
      obtained from US life tables, and QALE was estimated from a weighted combination
      of the EQ-5D scores and the life expectancy estimates. Outcomes were summarized
      by depression status for the four health behaviors (smoking, physical inactivity,
      heavy alcohol drinking, and obesity). RESULTS: For depressed adults, current
      smokers and the physically inactive had significantly lower EQ-5D scores (0.040
      and 0.171, respectively), shorter life expectancy (12.9 and 10.8 years,
      respectively), and substantially less QALE (8.6 and 10.9 years, respectively).
      For nondepressed adults, estimated effects were similar but smaller. Heavy
      alcohol drinking among depressed adults, paradoxically, was associated with
      higher EQ-5D scores but shorter life expectancy. Obesity was strongly associated
      with lower EQ-5D scores but only weakly associated with shorter life expectancy.
      CONCLUSIONS: Among depressed adults, physical inactivity and smoking were
      strongly associated with lower EQ-5D scores, life expectancy, and QALE, whereas
      obesity and heavy drinking were only weakly associated with these indices. These
      results suggest that reducing physical inactivity and smoking would improve
      health more among depressed adults.

PMID- 29566845
TI  - Erratum on "A short form of the neonatal intensive care unit family needs
      inventory".

PMID- 29566846
TI  - Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short
      Curriculum 2.0.
AB  - The degree of exposure to pediatric and adolescent gynecology (PAG) varies across
      residency programs in obstetrics and gynecology and pediatrics. Nevertheless,
      these programs are responsible for training residents and providing opportunities
      within their programs to fulfill PAG learning objectives. To that end, the North
      American Society for Pediatric and Adolescent Gynecology has taken a leadership
      role in PAG resident education by creating and systematically updating the Short
      Curriculum. This curriculum outlines specific learning objectives that are
      central to PAG education and lists essential resources for learners' reference.
      This updated curriculum replaces the previous 2014 publication with added
      content, resources, and updated references. Additionally, attention to the needs
      of learners in pediatrics and adolescent medicine is given greater emphasis in
      this revised North American Society for Pediatric and Adolescent Gynecology Short
      Curriculum 2.0.

PMID- 29566847
TI  - What is Pediatric and Adolescent Gynecology?

PMID- 29566848
TI  - Corrigendum to: Comparison of Induction Therapy in Non-high Risk Acute
      Promyelocytic Leukemia with Arsenic Trioxide or in Combination with ATRA Leukemia
      Research 66 (2018) 85-88.

PMID- 29566849
TI  - Pathogenesis of uterine adenomyosis: invagination or metaplasia?
AB  - Adenomyosis is a commonly diagnosed estrogen-dependent gynecological disorder
      that causes pelvic pain, abnormal uterine bleeding, and infertility. Despite its
      prevalence and severity of symptoms, its pathogenesis and etiology have not yet
      been elucidated. The aim of this manuscript is to review the different hypotheses
      on the origin of adenomyotic lesions and the mechanisms involved in the evolution
      and progression of the disease. Two main theories have been proposed to explain
      the origin of adenomyosis. The most common suggests involvement of tissue injury
      and the repair mechanism and claims that adenomyosis results from invagination of
      the endometrial basalis into the myometrium. An alternative theory maintains that
      adenomyotic lesions result from metaplasia of displaced embryonic pluripotent
      Mullerian remnants or differentiation of adult stem cells. Previous
      investigations performed in human adenomyotic lesions and corroborated by studies
      in mice supported the involvement of the epithelial-mesenchymal transition
      process in the early stages of progression and spread of adenomyosis. However,
      studies conducted in a recently developed baboon model indicate that collective
      cell migration may be implicated in the later events of invasion. This suggests
      that the invasiveness of this complex uterine disorder is not driven by a single
      mechanism of migration but by a time-dependent combination of two processes.

PMID- 29566850
TI  - Symptoms and classification of uterine adenomyosis, including the place of
      hysteroscopy in diagnosis.
AB  - Where histology used the presence of glands and/or stroma in the myometrium as
      pathognomonic for adenomyosis, imaging uses the appearance of the myometrium, the
      presence of striations, related to the presence of endometrial tissue within the
      myometrium, the presence of intramyometrial cystic structures and the size and
      asymmetry of the uterus to identify adenomyosis. Preliminary reports show a good
      correlation between the features detected by imaging and the histological
      findings. Symptoms associated with adenomyosis are abnormal uterine bleeding,
      pelvic pain (dysmenorrhea, chronic pelvic pain, dyspareunia), and impaired
      reproduction. However a high incidence of existing comorbidity like fibroids and
      endometriosis makes it difficult to attribute a specific pathognomonic symptom to
      adenomyosis. Heterogeneity in the reported pregnancy rates after assisted
      reproduction is due to the use of different ovarian stimulation protocols and
      absence of a correct description of the adenomyotic pathology. Current efforts to
      classify the disease contributed a lot in elucidated the potential
      characteristics that a classification system should be relied on. The need for a
      comprehensive, user friendly, and clear categorization of adenomyosis including
      the pattern, location, histological variants, and the myometrial zone seems to be
      an urgent need. With the uterus as a possible unifying link between adenomyosis
      and endometriosis, exploration of the uterus should not only be restricted to the
      hysteroscopic exploration of the uterine cavity but in a fusion with ultrasound.

PMID- 29566851
TI  - Role of transvaginal sonography and magnetic resonance imaging in the diagnosis
      of uterine adenomyosis.
AB  - The aim of the present review, conducted according to PRISMA statement
      recommendations, was to evaluate the contribution of transvaginal sonography
      (TVS) and magnetic resonance imaging (MRI) to diagnose adenomyosis. Although
      there is a lack of consensus on adenomyosis classification, three subtypes are
      described, internal, external adenomyosis, and adenomyomas. Using TVS, whatever
      the subtype, pooled sensitivities, pooled specificities, and pooled positive
      likelihood ratios are 0.72-0.82, 0.85-0.81, and 4.67-3.7, respectively, but with
      a high heterogeneity between the studies. MRI has a pooled sensitivity of 0.77,
      specificity of 0.89, positive likelihood ratio of 6.5, and negative likelihood
      ratio of 0.2 for all subtypes. Our results suggest that MRI is more useful than
      TVS in the diagnosis of adenomyosis. Further studies are required to determine
      the performance of direct signs (cystic component) and indirect signs
      (characteristics of junctional zone) to avoid misdiagnosis of adenomyosis.

PMID- 29566852
TI  - Role of medical therapy in the management of uterine adenomyosis.
AB  - Adenomyosis is a benign uterine condition affecting women at various ages with
      different symptoms. The management of these patients is still controversial. Few
      clinical studies focusing on medical or surgical treatment for adenomyosis have
      been performed. No drug is currently labelled for adenomyosis and there are no
      specific guidelines to follow for the best management. Anyhow, medical treatments
      are effective in improving symptoms (pain, abnormal uterine bleeding and
      infertility). The rationale for using medical treatment is based on the
      pathogenetic mechanisms of adenomyosis: sex steroid hormones aberrations,
      impaired apoptosis, and increased inflammation. Several nonhormonal (i.e.,
      nonsteroidal anti-inflammatory drugs) and hormonal treatments (i.e., progestins,
      oral contraceptives, gonadotropin-releasing hormone analogues) are currently used
      off-label to control pain symptoms and abnormal uterine bleeding in adenomyosis.
      Gonadotropin-releasing hormone analogues are indicated before fertility
      treatments to improve the chances of pregnancy in infertile women with
      adenomyosis. An antiproliferative and anti-inflammatory effect of progestins,
      such as dienogest, danazol and norethindrone acetate, suggests their use in
      medical management of adenomyosis mainly to control pain symptoms. On the other
      hand, the intrauterine device releasing levonorgestrel resulted is extremely
      effective in resolving abnormal uterine bleeding and reducing uterine volume in a
      long-term management plan. Based on new findings on pathogenetic mechanisms, new
      drugs are under development for the treatment of adenomyosis, such as selective
      progesterone receptor modulators, aromatase inhibitors, valproic acid, and anti
      platelets therapy.

PMID- 29566853
TI  - Uterine adenomyosis and adenomyoma: the surgical approach.
AB  - The appropriate surgical treatment of adenomyosis, a benign invasion/infiltration
      of endometrial glands within the underlying myometrium, remains a subject of
      discussion. Since 1990, in place of the classical V-shaped resection method,
      various kinds of surgical management have been attempted, including a uterine
      muscle flap method that emphasizes fertility preservation, an asymmetric
      dissection method, and various modified reduction methods. Laparoscopic
      adenomyomectomy has also become an alternative to laparotomy for surgically
      managing the focal type of adenomyosis, although it seems to be associated with a
      higher risk of uterine rupture than laparotomy. This article reviews the surgical
      treatment of adenomyosis, including 23 uterine rupture cases that occurred during
      post-adenomyomectomy pregnancies, and provides an updated picture of the state of
      the field.

PMID- 29566854
TI  - The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee
      opinion.
AB  - The value of preimplantation genetic testing for aneuploidy (PGT-A) as a
      screening test for in vitro fertilization (IVF) patients has yet to be
      determined. Several studies demonstrate higher birth rates after aneuploidy
      testing and elective single-embryo transfer (eSET), suggesting the potential for
      this testing to decrease the risk of multiple gestations, though these studies
      have important limitations.

PMID- 29566855
TI  - Cumulus cell gene expression as a potential biomarker for oocyte quality.

PMID- 29566856
TI  - Take your time.

PMID- 29566857
TI  - Overcoming barriers to providing HIV prevention for HIV serodiscordant couples
      desiring pregnancy.

PMID- 29566858
TI  - Ovarian tissue cryopreservation: still experimental?

PMID- 29566859
TI  - Predicting the recurrence of endometrial polyps: a commentary.

PMID- 29566860
TI  - Beyond decreased ovarian reserve: considering reproductive comorbidities in
      female cancer survivors.

PMID- 29566861
TI  - Continuum of polycystic ovary syndrome physiology.

PMID- 29566864
TI  - Evidence-Based Insights into the Utility of Conjunctival Biopsy in Mucous
      Membrane Pemphigoid.

PMID- 29566865
TI  - Multimodal Imaging in Adult-Onset Coats' Disease.

PMID- 29566862
TI  - Male sleep duration and fecundability in a North American preconception cohort
      study.
AB  - OBJECTIVE: To evaluate prospectively the association between male sleep duration
      and fecundability. DESIGN: Pregnancy Online Study (PRESTO), a Web-based
      prospective cohort study of North American couples enrolled during the
      preconception period (2013-2017). SETTING: Not applicable. PATIENT(S): Male
      participants were aged >=21 years; female participants were aged 21-45 years.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): At enrollment, men reported their
      average nightly sleep duration in the previous month. Pregnancy status was
      updated on female follow-up questionnaires every 8 weeks for up to 12 months or
      until conception. Analyses were restricted to 1,176 couples who had been
      attempting to conceive for up to six cycles at enrollment. Proportional
      probabilities regression models were used to estimate fecundability ratios (FRs)
      and 95% confidence intervals (CIs), adjusting for potential confounders.
      RESULT(S): Relative to 8 hours per night of sleep, multivariable-adjusted FRs for
      <6, 6, 7, and >=9 hours per night of sleep were 0.62 (95% CI 0.45-0.87), 1.06
      (95% CI 0.87-1.30), 0.97 (95% CI 0.81-1.17), and 0.73 (95% CI 0.46-1.15),
      respectively. The association between short sleep duration (<6 hours per night)
      and fecundability was similar among men not working nights or rotating shifts (FR
      0.60, 95% CI 0.41-0.88) and among men without a history of infertility (FR 0.62,
      95% CI 0.44-0.87) and was stronger among fathers (FR 0.46, 95% CI 0.28-0.76).
      CONCLUSION(S): Short sleep duration in men was associated with reduced
      fecundability. Because male factor accounts for 50% of couple infertility,
      identifying modifiable determinants of infertility could provide alternatives to
      expensive fertility workups and treatments.

PMID- 29566863
TI  - Establishing a Vision and Eye Health Surveillance System for the Nation: A Status
      Update on the Vision and Eye Health Surveillance System.

PMID- 29566866
TI  - Oculodermal Melanocytosis, Darker Complexion, Choroidal Melanoma: A Missed Clue.

PMID- 29566867
TI  - Iris-Fixated Phakic Intraocular Lenses: New Results.

PMID- 29566868
TI  - Bilateral Asymptomatic Cryptococcal Retinitis without Choroiditis or Vitritis.

PMID- 29566869
TI  - Clinicopathologic Correlation of Choroidal Invasion in Retinoblastoma.

PMID- 29566871
TI  - Corrigendum.

PMID- 29566870
TI  - Infraorbital Nerve Involvement on Magnetic Resonance Imaging in Igg4-Related
      Ophthalmic Disease: A Highly Suggestive Sign.

PMID- 29566872
TI  - Re: Schlenker et al.: Efficacy, safety, and risk factors for failure of
      standalone ab interno gelatin microstent implantation versus standalone
      trabeculectomy. (Ophthalmology. 2017;124:1579-1588).

PMID- 29566873
TI  - Reply.

PMID- 29566874
TI  - Reply.

PMID- 29566875
TI  - Re: De Moraes et al.: 24-2 Visual fields miss central defects shown on 10-2 tests
      in glaucoma suspects, ocular hypertensives, and early glaucoma (Ophthalmology.
      2017;124:1449-1456).

PMID- 29566876
TI  - Re: Reddy et al.: Vitrectomy and vitrector port needle biopsy of choroidal
      melanoma for gene expression profile testing immediately before brachytherapy.
      (Ophthalmology. 2017;124:1377-1382).

PMID- 29566877
TI  - Reply.

PMID- 29566878
TI  - Re: Francis et al.: Clinical and morphologic characteristics of MEK inhibitor
      associated retinopathy: differences from central serous chorioretinopathy
      (Ophthalmology. 2017;124:1788-1798).

PMID- 29566879
TI  - Reply.

PMID- 29566880
TI  - Mastocytosis With Associated Essential Thrombocythemia.

PMID- 29566881
TI  - Extragenital Lichen Sclerosus Induced by Radiotherapy.

PMID- 29566882
TI  - Auditory steady-state response in cochlear implant patients.
AB  - INTRODUCTION AND OBJECTIVE: Auditory steady state responses to continuous
      amplitude modulated tones at rates between 70 and 110Hz, have been proposed as a
      feasible alternative to objective frequency specific audiometry in cochlear
      implant subjects. The aim of the present study is to obtain physiological
      thresholds by means of auditory steady-state response in cochlear implant
      patients (Clarion HiRes 90K), with acoustic stimulation, on free field conditions
      and to verify its biological origin. METHODS: 11 subjects comprised the sample.
      Four amplitude modulated tones of 500, 1000, 2000 and 4000Hz were used as
      stimuli, using the multiple frequency technique. The recording of auditory steady
      state response was also recorded at 0dB HL of intensity, non-specific stimulus
      and using a masking technique. RESULTS: The study enabled the
      electrophysiological thresholds to be obtained for each subject of the explored
      sample. There were no auditory steady-state responses at either 0dB or non
      specific stimulus recordings. It was possible to obtain the masking thresholds. A
      difference was identified between behavioral and electrophysiological thresholds
      of -6+/-16, -2+/-13, 0+/-22 and -8+/-18dB at frequencies of 500, 1000, 2000 and
      4000Hz respectively. CONCLUSIONS: The auditory steady state response seems to be
      a suitable technique to evaluate the hearing threshold in cochlear implant
      subjects.

PMID- 29566883
TI  - A rare case of a venous malformation of the clitoris.

PMID- 29566884
TI  - Adolescent With Pain in the Left Knee.

PMID- 29566886
TI  - For Low-Risk Patients With Suspected Acute Coronary Syndrome, Should Urgent (72
      hours) Non-Invasive Cardiac Testing Be Performed After Biomarker Exclusion of
      Acute Myocardial Infarction.

PMID- 29566885
TI  - Man With Leg Pain.

PMID- 29566887
TI  - Defer Urgent Noninvasive Testing in Low-Risk Chest Pain Patients.

PMID- 29566888
TI  - Resuscitation of a Patient With an Implanted Electronic Device.

PMID- 29566889
TI  - Man With Heart Palpitations.

PMID- 29566890
TI  - The Clue Is in the U Wave: Torsades de Pointes Ventricular Tachycardia in a
      Hypokalemic Woman on Methadone.

PMID- 29566891
TI  - Abnormal P and QRS Axes in a Young Male With a Stab Wound to the Chest.

PMID- 29566892
TI  - Out With the Old, In With the Flu.

PMID- 29566893
TI  - Closing the Circle.

PMID- 29566894
TI  - Medicaid and Moral Hazard: Covering Emergency Department Visits Increases
      Emergency Department Visits...or Not?: Answers to the November 2017 Journal Club
      Questions.

PMID- 29566895
TI  - A Male Teenager With Dysuria.

PMID- 29566896
TI  - Posttraumatic Stress Disorder in Emergency Medicine Residents: A Reply and
      Caveat.

PMID- 29566897
TI  - In reply.

PMID- 29566898
TI  - Getting to the Point of Ultrasonography in Cardiac Arrest.

PMID- 29566899
TI  - In reply.

PMID- 29566900
TI  - Young Girl With Right Flank Pain.

PMID- 29566902
TI  - Preface to "Gut microbiome in health and disease".

PMID- 29566901
TI  - Young Boy With Fatigue and Weight Loss.

PMID- 29566903
TI  - The gastrointestinal microbiota and its role in oncogenesis.
AB  - Advances in research techniques have made it possible to map the microbial
      communities in the gastrointestinal (GI) tract, where the majority of bacteria in
      the human body reside. Disturbances in these communities are referred to as
      dysbiosis and have been associated with GI cancers. Although dysbiosis is
      observed in several GI malignancies, the specific role of these changes has not
      been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC).
      This review will address the bacterial communities along the GI tract, from the
      oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and
      carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in
      gastric carcinogenesis, the same may hold true for other GI tract malignancies,
      where an interplay between microbes in carcinogenesis seems conceivable,
      especially in colorectal cancer (CRC). In the last part of this review we will
      discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.

PMID- 29566904
TI  - Microbiome measurement: Possibilities and pitfalls.
AB  - Microbiome research is an emerging field in medical sciences. Several studies
      have made headways in understanding the influence of microbes on our health and
      disease states. Further progress in mapping microbiome populations across
      different body sites and understanding the underlying mechanisms of microbiome
      host interactions depends critically on study design, collection protocols,
      analytical genetic techniques, and reference databases. In particular, a shift
      has appeared going from small sample collections to large-scale population
      studies (with extensive phenotypic information including disease status) which
      calls for some adaptions. In this review we will focus on gut microbiome
      profiling using the 16S ribosomal RNA approach in the setting of large-scale
      population studies, and discuss some novel developments.

PMID- 29566905
TI  - Lifestyle alters GUT-bacteria function: Linking immune response and host.
AB  - Microbiota in human is a "mixture society" of different species (i.e. bacteria,
      viruses, funguses) populations with a different way of relationship
      classification to Human. Human GUT serves as the host of the majority of
      different bacterial populations (GUT flora, more than 500 species), which are
      with us ("from the beginning") in an innate manner known as the commensal (no
      harm to each other) and symbiotic (mutual benefit) relationship. A homeostatic
      balance of host-bacteria relationship is very important and vital for a normal
      health process. However, this beneficial relationship and delicate homeostatic
      state can be disrupted by the imbalance of microbiome-composition of gut
      microbiota, expressing a pathogenic state. A strict homeostatic balance of
      microbiome-composition strongly depends on several factors; 1- lifestyle, 2-
      geography, 3- ethnicities, 4- "mom" as prime of the type of bacterial
      colonization in infant and 5- the disease. With such diversity in individuals
      combined with huge number of different bacterial species and their interactions,
      it is wise to perform an in-depth systems biology (e.g. genomics, proteomics,
      glycomics, and etcetera) analysis of personalized microbiome. Only in this way,
      we are able to generate a map of complete GUT microbiota and, in turn, to
      determine its interaction with host and intra-interaction with pathogenic
      bacteria. A specific microbiome analysis provides us the knowledge to decipher
      the nature of interactions between the GUT microbiota and the host and its
      response to the invading bacteria in a pathogenic state. The GUT-bacteria
      composition is independent of geography and ethnicity but lifestyle well affects
      GUT-bacteria composition and function. Microbiome knowledge obtained by systems
      biology also helps us to change the behavior of GUT microbiota in response to the
      pathogenic microbes as protection. Functional microbiome changes in response to
      environmental factors will be discussed in this review.

PMID- 29566906
TI  - Action and function of Akkermansia muciniphila in microbiome ecology, health and
      disease.
AB  - The discovery of Akkermansia muciniphila has opened new avenues for the use of
      this abundant intestinal symbiont in next generation therapeutic products, as
      well as targeting microbiota dynamics. A. muciniphila is known to colonize the
      mucosal layer of the human intestine where it triggers both host metabolic and
      immune responses. A. muciniphila is particularly effective in increasing mucus
      thickness and increasing gut barrier function. As a result host metabolic markers
      ameliorate. The mechanism of host regulation is thought to involve the outer
      membrane composition, including the type IV pili of A. muciniphila, that directly
      signal to host immune receptors. At the same time the metabolic activity of A.
      muciniphila leads to the production of short chain fatty acids that are
      beneficial to the host and microbiota members. This contributes to host
      microbiota and microbe-microbe syntrophy The mucolytic activity and metabolite
      production make A. muciniphila a key species in the mucus layer, stimulating
      beneficial mucosal microbial networks. This well studied member of the microbiota
      has been studied in three aspects that will be further described in this review:
      i) A. muciniphila characteristics and mucin adaptation, ii) its role as key
      species in the mucosal microbiome, and iii) its role in host health.

PMID- 29566907
TI  - Action and function of Faecalibacterium prausnitzii in health and disease.
AB  - Faecalibacterium prausnitzii, anaerobic bacteria, is one of the main components
      of gut microbiota and the most important butyrate-producing bacteria in the human
      colon. So far, this commensal bacterium has been considered as a bioindicator of
      human health, once when its population is altered (decreased), inflammatory
      processes are favored. Several reports in the literature highlighted that the
      amount of Faecalibacterium prausnitzii negatively correlates to the activity of
      inflammatory bowel disease and colorectal cancer. Therefore, counterbalancing
      dysbiosis using Faecalibacterium prausnitzii as a potential active component of
      probiotic formulations appears to be a promising therapeutic strategy for
      inflammatory bowel diseases and colorectal cancer. However, once this microbial
      is very sensitive to oxygen, the formulation development is a great challenge. In
      this review, we will focus our attention on Faecalibacterium prausnitzii biology,
      anti-inflammatory metabolites, modulators of this bacterium population and its
      impact on human health.

PMID- 29566908
TI  - Action and function of Chromobacterium violaceum in health and disease: Violacein
      as a promising metabolite to counteract gastroenterological diseases.
AB  - Chromobacterium violaceum is a Gram negative, beta-proteobacterium found in the
      microbiota of tropical and subtropical environments. Although considered an
      opportunistic pathogen, infection rapidly progress to fatal sepsis, with
      metastatic abscesses. It is noteworthy the multidrug resistant phenotype of C.
      violaceum and the possibility of relapse. Recently, an influence of global
      climate in the incidence of cases beyond the previous areas has been observed.
      Furthermore, chronic granulomatous disease has been considered a risk factor to
      infection. Despite the increase in C. violaceum infection incidence and high
      mortality, most clinicians are not familiar with it. This review pointed out
      important features of this life threatening microorganism, including its
      pathogenicity, mechanistic aspects, genetic and drug resistance associated
      factors, and the clinical association with chronic granulomatous disease. In
      addition, its main metabolite violacein may be a promising agent to counteract
      gastroenterological diseases, such as colorectal cancer and inflammatory gastric
      lesions.

PMID- 29566909
TI  - NAFLD, Helicobacter species and the intestinal microbiome.
AB  - Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic
      liver disease worldwide. It is well-accepted that gut dysbiosis is associated
      with NAFLD, however, there is some conflicting evidence regarding the nature of
      these alterations. Infection with Helicobacter species, mainly H. pylori, has
      also been associated with increased NAFLD risk, however, some studies have failed
      to reproduce this finding. Further studies including large study samples and
      standardised procedures for microbiota analyses, H. pylori detection and NAFLD
      diagnostic criteria, are required. The mechanisms involving Helicobacter species
      and the intestinal microbiome in NAFLD pathogenesis appear to be part of the
      multiple-hit theory, in which increased intestinal permeability, inflammatory
      responses, altered choline, bile acids and carbohydrate metabolism, production of
      short-chain fatty acids, urea cycle and urea transport systems, altered
      maintenance of hepatic gammadeltaT-17 cells, insulin resistance, hormones
      secreted by the adipose tissue, metabolic hormones, bacterial metabolites and
      Helicobacter toxins, are all implicated.

PMID- 29566910
TI  - Intestinal microbiome and permeability in patients with autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a severe inflammatory liver disease. The underlying
      mechanisms remain unclear, but recent studies provided new perspectives on
      altered intestinal microbiome and permeability in AIH animal models and patients,
      highlighting gut-liver crosstalk in the pathogenesis of AIH. Transgenic AIH mice
      carrying HLA-DR3 showed reduced diversity and total load of gut microbiota. Germ
      free mice are resistant to concanavalin A-induced liver injury, whereas
      enterogenouss antigens induce the activation of natural killer T cells
      participating in concanavalin A-induced liver injury, supporting the close
      relationship between microbiota and AIH. Moreover, 'molecular mimicry' provides a
      plausible interpretation of the immune reactions between microorganic antigens
      and liver autoantigens, for instance, cytochrome P4502D6, the target of cross
      reactivity between virus and self. Nevertheless, direct evidence for the
      intestinal microbiome and permeability in AIH is still limited. The relationship
      between AIH susceptibilities and an intestinal microbiome shaped by drugs, diets
      or genes needs further study.

PMID- 29566911
TI  - Diet, microbiome, and colorectal cancer.
AB  - The scientific interests in the colorectal cancer (CRC) associated microbiome
      have increased significantly in the past decade. Mechanistically, several members
      of the human microbiome and products thereof have been implicated as inductors of
      the pathogenic inflammation related to CRC. Conversely, the activities of the
      human intestinal microbial community influenced by specific diet might confer a
      protective effect against the CRC risks and progression. As the microbiome is
      both a key contributor and one of the tools to prevent CRC, the current review
      gives a summary of the CRC-associated microbiome and the dietary strategies
      relevant to CRC. As more evidences become available, new microbiome-based
      treatments and specific diets may emerge to reduce the CRC risk and improve CRC
      patients' quality of life.

PMID- 29566912
TI  - Microbiome, pattern recognition receptor function in health and inflammation.
AB  - The innate immune system plays an important role in shaping the microbiota into
      configurations that are tolerated and beneficial to the host, thereby playing a
      crucial role in human health. Innate immunity is based on the fundamental
      principle that Pattern Recognition Receptors (PRRs) recognise pathogen associated
      molecular patterns as non-self-entities and trigger intracellular signalling
      pathways that lead to the induction of numerous cytokines and chemokines that
      help maintain host resistance to infections. Dysregulation of this interaction
      has been identified as the core defect that leads to chronic intestinal
      inflammation allowing certain microbiota to be harmful to host health. This
      dysbiosis of the microbiome is found associated with numerous chronic diseases. A
      logical explanation would be that genetic defects in the recognition and response
      pathways that the host uses to identify these microbial pathogens could lead to
      altered microbial colonisation or mis-recognition of normal bacteria leading to
      diseases. The interaction between pattern recognition receptors, microbial traits
      and human health with respect to the gut are now rapidly resolved and will be the
      subject of this review.

PMID- 29566913
TI  - Intervening in disease through genetically-modified bacteria.
AB  - The comprehension of the molecular basis of different diseases is rapidly being
      dissected as a consequence of advancing technology. Consequently, proteins with
      potential therapeutic usefulness, including cytokines and signaling molecules
      have been identified in the last decades. However, their clinical use is hampered
      by disadvantageous functional and economic considerations. One of the most
      important of these considerations is targeted topical delivery and also the
      synthesis of such proteins, which for intravenous use requires rigorous
      purification whereas proteins often do not withstand digestive degradation and
      thus cannot be applied per os. Recently, the idea of using genetically modified
      bacteria has emerged as an attempt to evade these important barriers. Using such
      bacteria can deliver therapeutic proteins or other molecules at place of disease,
      especially when disease is at a mucosal surface. Further, whereas intravenously
      applied therapeutic proteins require expensive methodology in order to become
      endotoxin-free, this is not necessary for local application of therapeutic
      proteins in the intestine. In addition, once created further propagation of
      genetically modified bacteria is both cheap and requires relatively little in
      conditioning with respect to transport of the medication, making such organisms
      also suitable for combating disease in developing countries with poor
      infrastructure. Although first human trials with such bacteria were already
      performed more as a decade ago, the recent revolution in our understanding of the
      role of human gut microbiome in health and diseases has unleashed a revolution in
      this field resulting in a plethora of potential novel prophylactic and
      therapeutic intervention against disease onset and development employing such
      organisms. Today, the engineering of human microbiome for health benefits and
      related applications now chances many aspects of biology, nanotechnology and
      chemistry. Here, we review genetically modified bacteria methodology as possible
      carriers of drug delivering and provided the origin and inspirations for new drug
      delivery systems.

PMID- 29566914
TI  - The mature patient: Geriatric dermatology.

PMID- 29566915
TI  - Skin barrier and dry skin in the mature patient.
AB  - Dry skin is the most common clinical manifestation of dermatologic diseases, and
      it presents with itching, redness, and desquamation-signs and clinical
      manifestations that are not only physically uncomfortable but also affect
      patients psychologically. The water content in the stratum corneum is largely
      dependent on the composition and amount of the intercellular lipids, which
      regulate the loss of water from the skin, and on the levels of hygroscopic
      substances of the natural moisturizing factors, which are responsible for
      retention of water in the stratum corneum. Prevention of water loss and
      penetration of potentially toxic substances and microorganisms into the body are
      the most important functions of the skin, which acts as a natural frontier
      between the inner organism and the environment. Skin barrier defects occur in
      several skin diseases, but the influence of aging on the skin barrier function is
      largely unknown and conflicting results have been reported. In this review, the
      structure and function of the barrier in relation to the aging process are
      discussed.

PMID- 29566916
TI  - Diagnostic challenges in the mature patient: Growing old gracefully.
AB  - Skin diseases in the elderly are frequent and sometimes misleading, due to age
      related changes that alter the clinical presentation. Clinicopathologic
      correlation is often the clue for distinguishing among various pathologies for
      which clinical signs are more striking than the histopathologic findings.
      Pitfalls are always lying in wait to ambush inexperienced dermatologists, but
      usually the microscope provides subtle hints to solve the quandary. In an attempt
      to familiarize physicians with emerging skin care demands of older patients, we
      have reviewed major diagnostic challenges in this group of patients: age-related
      changes, more common skin pathologies in mature patients, manifestations of
      comorbidity, skin tumors, and paraneoplastic syndromes.

PMID- 29566917
TI  - Therapeutic challenges in the mature patient.
AB  - With the tremendous increase in the proportion of seniors in the global
      population, geriatric health care has become of greater interest and concern.
      Increased emphasis on geriatric medicine, along with the growth in the
      development of age-related skin disorders, has led to particular attention for
      geriatric, dermatology and dermatopharmacology. An aging population has brought
      many therapeutic challenges that we need to recognize and overcome by applying
      geropharmacologic principles. The purpose of this paper is to inform
      dermatologists of the age-related changes in the pharmacokinetics of common
      dermatologic drugs, their various interactions potentially occurring in the
      elderly, and the principles and evidence-based strategies for detection,
      management, and prevention to improve medication adherence. By implementing these
      principles and strategies, we can ensure the best and the safest treatment to
      promote the desired therapeutic outcome and improved quality of life for this
      fragile subpopulation.

PMID- 29566918
TI  - Causes, pathophysiology, and treatment of pruritus in the mature patient.
AB  - Chronic itch is a common and debilitating health condition in the elderly. There
      are several common causes of itch in the mature population, such as skin xerosis,
      immunosenescence, and neuropathic changes. In addition, skin diseases, such as
      seborrheic dermatitis and stasis dermatitis, systemic conditions (end-stage renal
      disease and diabetes), or psychogenic derailments, such as depression, anxiety,
      and dementia, can all serve as triggers of pruritus. Polypharmacy, a common
      occurrence among the elderly population, may also serve as a cause of itch that
      may or may not be accompanied by dermatitis. Such medications as MU opioids and
      calcium channel blockers have been found to have a connection with pruritus in
      the advanced aging population. Determining the exact trigger for pruritus in the
      elderly may be especially challenging, because itch can be idiopathic in many
      cases. The role of treatments should not only take into account elimination of
      various underlying cutaneous, systemic, or psychogenic conditions associated with
      itch but also focus on the skin changes that are characteristic of the aging
      process. Development of such treatment options can be guided by elucidation of
      the mechanisms underlying the pathophysiology of itch in the geriatric
      population.

PMID- 29566919
TI  - Facial changes in the mature patient.
AB  - During the aging process, the appearance of the human face changes significantly
      due to fundamental alterations in the bones, soft tissues, and skin. Both
      endogenous and environmental factors are involved in age-related transformations
      of the face; however, facial skin is particularly influenced by environmental
      factors, and the risk of overexposure and consequent premature facial aging. This
      review summarizes the current state of knowledge of the most common facial skin
      changes in the mature patient, including pathogenesis of both intrinsic and
      extrinsic skin aging, as well as clinical and histologic features of skin aging.
      Because the majority of facial skin changes in the elderly develop as the
      consequence of ultraviolet radiation, these can be prevented by adequate
      photoprotection.

PMID- 29566920
TI  - Hair and nail diseases in the mature patient.
AB  - The elderly population is growing, lifespans are increasing, and a greater
      emphasis on geriatric care is being implemented in hospital systems. With a
      higher percentage of the population living longer, hair and nail diseases
      associated with the advanced stages of life are becoming more prevalent. Common
      hair diseases in the elderly include androgenetic alopecia, senile alopecia,
      frontal fibrosing alopecia, and erosive pustular dermatosis of the scalp. Nail
      diseases associated with advanced age include onychomycosis, brittle nails,
      onychocryptosis, onychoclavus, onychogryphosis, subungual hematomas, subungual
      exostosis, myxoid cysts, and malignancies. These diseases can have a serious
      impact on a patient's quality of life. In an effort to familiarize the reader
      with these common changes and abnormalities, we discuss hair and nail diseases in
      the mature patient.

PMID- 29566921
TI  - Epidemiology of skin cancer in the mature patient.
AB  - Epidermal cancers include keratinocyte cancer, melanocyte cancer, and Merkel cell
      carcinoma. These cancers account for the vast majority of new cancers diagnosed
      in Australia, North America, and Europe. Keratinocyte cancer is the most common
      epidermal cancer and accounts for 7 out of 8 new cancers diagnosed in Australia.
      Melanoma and Merkel cell carcinoma are less common than keratinocyte carcinoma
      but are more important causes of mortality in Australia. Keratinocyte cancer has
      also been demonstrated to be a marker of cancer-prone phenotype. Risk factors for
      epidermal cancer include intrinsic and environmental factors, in particular
      exposure to ultraviolet radiation and advanced age. Actinic keratosis has an
      approximate prevalence of 79% of men and 68% of women between 60 and 69 years of
      age, and has a low risk of malignant transformation into squamous cell carcinoma.
      Basal cell carcinoma is the most common malignancy in Caucasians worldwide, with
      the incidence increasing by 2% per year in Australia. Squamous cell carcinoma is
      the second most common epidermal cancer, with an incidence of approximately 1035
      or 472 per 100,000 person-years in men and women, respectively. Primary risk
      factors for both basal cell carcinoma and squamous cell carcinoma include light
      skin color, UV radiation exposure, and chronic immunosuppression. Although the
      rate of melanoma is increasing, the mortality in Australia is reducing and is
      currently 9%. The overall incidence of melanoma in Australia is approximately 50
      cases per 100,000 persons (62 for men and 40 for women). Keratinocyte carcinoma
      and melanoma are risk factors for developing further skin cancer and primary
      malignancy. This contribution reviews the incidence, prevalence, and risk factors
      associated with the development of epidermal cancer and premalignant epidermal
      neoplasia.

PMID- 29566922
TI  - Nonsurgical treatment of nonmelanoma skin cancer in the mature patient.
AB  - Nonmelanoma skin cancer (NMSC) is the most common cancer, with the median age at
      NMSC diagnosis is 71 years. Treatment options for NMSC include surgical therapy,
      which is usually the first-choice treatment, and nonsurgical modalities.
      Therapeutic modalities depend on tumor localization, histologic type, and
      biologic behavior, as well as patient comorbidities, age, and life expectancy.
      Nonsurgical treatments include cryotherapy, local therapies (imiquimod, 5
      fluorouracil, ingenol mebutate, and diclofenac), photodynamic therapy,
      radiotherapy, and hedgehog inhibitors. Some of these treatments can be combined
      with curettage and electrodesiccation for better outcomes. Every treatment
      modality has advantages and disadvantages that must be carefully considered
      individually. Because the facial area is the most common localization of NMSC,
      treatment modalities with better cosmetic outcome are preferred. Although NMSC
      mostly occurs in the elderly, this review is focused on the features and
      nonsurgical therapy of NMSC in deep old age (>=85) and long-lived persons (aged
      >95); however, clinical trials very rarely involve this population group due to
      poor cooperation or poor general condition of these patients; thus, the
      respective knowledge being generally based on clinical experience.

PMID- 29566923
TI  - Cutaneous infections in the mature patient.
AB  - Dermatologists must be familiar with the peculiarities of the micro-organisms
      that may affect the elderly, in order to optimize the diagnosis and treatment of
      infections, which may affect their skin, especially because the world population
      is rapidly aging. It is estimated that there will be 434 million individuals over
      80 years of age in 2050. Since the elderly population is rapidly increasing and
      their infections are usually more severe and different from those observed in
      younger adults, it leads to a statistical increase of the rates regarding
      hospitalization and mortality caused by infectious diseases among people over 85
      years. Other health issues may be involved in the older population. These include
      nutritional alterations, as malnutrition or obesity, which can aggravate the
      infections. Also the usual signs and symptoms of infection are subtle or
      uncharacteristic in elderly patients, and frequently, they are unable to report
      their symptoms, which can delay the diagnosis. Among the many infections that may
      affect the elderly we reviewed the most frequent and those that are different in
      this age group, as herpes zoster, cytomegalovirus, herpes simplex, bacterial skin
      infections, erysipelas, celullitis, impetigo, folliculitis, furunculosis and
      carbunculosis, secondary infections, intertrigo (body folds), fungal infection,
      and scabies.

PMID- 29566924
TI  - Genital diseases in the mature man.
AB  - Elderly men are at higher risk of developing genital dermatologic problems,
      including inflammatory and neoplastic conditions due to age-related physiologic
      changes, immunosenescence, comorbidities, and iatrogenesis. Clinical
      manifestations of genital dermatoses in men are varied and may include itching,
      pain, redness, dermatitis, lumps, and ulcers. Even when asymptomatic, the
      psychologic impact may be significant. Sexual or urinary dysfunction may
      complicate genital dermatoses. Early and accurate diagnosis is essential to
      reduce morbidity and mortality from premalignant and malignant conditions and
      also to prevent sexual dysfunction and unnecessary anxiety in the case of benign
      entities.

PMID- 29566925
TI  - Genital diseases in the mature woman.
AB  - Vulvovaginal conditions are common in mature women. This reflects age-related
      changes in immunity and skin barrier function of vulvovaginal tissues. Vaginal
      atrophy is commonly complicated by dryness and inflammation, which makes
      postmenopausal atrophic vaginitis a virtually ubiquitous condition. The
      differential of vaginitis includes inflammatory, infectious, and malignant
      diseases, plus drug hypersensitivity. Atrophic vaginitis is treated with estrogen
      replacement therapy. Vulvovaginal malignant melanoma occurs predominantly in
      postmenopausal women and carries a poor prognosis. Similarly, the incidence of
      vulvovaginal malignancies, such as squamous cell carcinoma and extramammary Paget
      disease, rises exponentially after 65 years of age. Early diagnosis of these
      malignancies is of utmost importance. Lichen sclerosus et atrophicus and
      vulvovaginal candidosis are among the most common postmenopausal vulvovaginal
      conditions. Lichen sclerosus et atrophicus is associated with significant
      morbidity, and its management can be challenging. The incidence of vulvovaginal
      candidosis increases in patients on estrogen replacement therapy.

PMID- 29566926
TI  - Psoriasis in the mature patient: Therapeutic approach in the era of biologics.
AB  - Management of psoriasis in elderly patients may be challenging due to a small
      number of studies investigating this specific population. When treating a mature
      patient, special consideration should be given to multiple comorbidities,
      progressive functional impairment of several organs, immunosenescence, possible
      adverse effects, and polypharmacy. Due to the chronic nature of the disease and
      continuing rise in life expectancy, the prevalence of psoriasis among elderly is
      also expected to rise. Because many different therapies are available for
      treatment of psoriasis, we have reviewed those that have been investigated in the
      aging population. Although biologics have revolutionized the therapy of psoriasis
      due to targeted mechanism of action, high efficacy and low rate of adverse
      events, studies on the elderly population with psoriasis are scarce. Further
      clinical research and development of specific treatment guidelines in geriatric
      population are needed to optimize the therapeutic approach in this population.

PMID- 29566927
TI  - Blistering diseases in the mature patient.
AB  - Autoimmune blistering diseases (AIBD) are a group of chronic diseases affecting
      the skin and mucous membranes, with different presentation, clinical course,
      histologic and immunopathologic findings, and different therapeutic approach.
      Blisters develop as a result of autoantibodies directed against distinct adhesion
      structures within desmosomes or within the basement membrane zone. The most
      common AIBD that develops in the elderly is bullous pemphigoid (previously also
      named "pemphigoid senilis"), but mature patients can also present with other AIBD
      as mucous membrane pemphigoid, epidermolysis bullosa acquisita, paraneoplastic
      pemphigus, pemphigus vulgaris, pemphigus foliaceus, linear IgA dermatosis, and
      dermatitis herpetiformis. There are no differences in treatment approach to
      mature patients with AIBD, but due to more common comorbidities, systemic therapy
      should be given with more caution and control, and due to distorted skin
      integrity in the aged skin, the safety concerns are increased with the long-term
      use of any topical medication.

PMID- 29566928
TI  - Vascular diseases in the mature patient.
AB  - Aging results in both anatomic and physiologic changes in the skin's structure
      and vascular system. These vascular changes result in a wide array of
      dermatologic findings, ranging from the benign to the highly morbid. Herein, we
      review the impact of both intrinsic and common extrinsic factors of aging on
      cutaneous vasculature and highlight the manifestations of microvascular, venous,
      arterial, lymphatic, and neuropathic alterations in the geriatric population.

PMID- 29566929
TI  - Drug eruptions in the mature patient.
AB  - The world's population is now ageing at an unprecedented rate. Declining
      fertility and improved health and longevity have generated rising numbers and
      proportions of the older population in most parts of the world. With advancing
      age, however, comes an increasing incidence of disease (comorbidity or
      multimorbidity), an increasing use of medications (polypharmacy), and
      consequently an increase in adverse drug reactions (ADRs). Age-related changes in
      pharmacodynamics and pharmacokinetics (eg, volumes of drug distribution,
      metabolism and clearance, altered drug responsiveness and toxicity) and greater
      vulnerability to ADRs are other reasons for the higher incidence of ADRs in the
      elderly compared with young adults. Because the clinical patterns of ADRs are
      very similar for all age groups, including the elderly, the present review will
      deal mainly with statistics and numbers, rather than the clinical and/or disease
      patterns.

PMID- 29566930
TI  - Chronic immunosuppression in the mature patient.
AB  - In the ever-aging population of the world, the field of geriatrics continues to
      grow in importance. As human beings age, the skin undergoes a unique array of
      changes that predispose it to a specific set of dermatoses, infections, and
      neoplasms. Some of these physiologic alterations are comparable to the changes
      that happen in immunosuppressed individuals. Given the importance of
      immunosuppressive medications in treatment of many common skin conditions, we
      have reviewed the current literature to assist the practicing clinician in using
      immunosuppressive medications in the geriatric population.

PMID- 29566931
TI  - Signs of physical abuse and neglect in the mature patient.
AB  - Neglect and physical abuse of elderly are worrisome health problems, which are
      expected to grow even further, considering the aging of the population. By 2060,
      the number of people aged above 65 years is expected to double, whereas birth
      rates are low. This trend will cause a significant imbalance between different
      age groups and put more senior adults at risk for abuse. Risk factors, associated
      with abuse and neglect, are well established and can be categorized in
      sociodemographic-, victim-, or perpetrator-related risk factors. The effects of
      these risk factors depend mainly on the setting, which can be community-dwelling
      or institutionalized older adults. In community-based settings, 90% of
      perpetrators are family members. In each setting, suspicious physical injuries
      should be recognized and addressed promptly. This can be very challenging in
      elderly, among others, due to the age-related skin changes, which can mimic
      abuse; however, there are some cutaneous clues that should always raise suspicion
      of abuse, such as patterned shape or distribution, different healing stages of
      wounds, parallel injuries, signs of blunt trauma, and irregular patches of
      alopecia. General awareness is needed, and the advice of dermatologists, who are
      best trained to differentiate between those lesions, should be systematically
      sought, to reduce false-positive and false-negative interpretations.

PMID- 29566932
TI  - The status of the seborrheic keratosis.
AB  - Seborrheic keratosis (SK), whose appearance is generally a small roundish reddish
      to brownish scaling lesion ranging in size from a few mm to many mm, may have a
      single presentation or be one of many such lesions. Because it is a commonly
      encountered lesion on the face, trunk, or extemities and is readily recognized
      clinically, it is infrequently biopsied. When the lesion has an unusual pattern
      or has become irritated, it may rarely mimic a malignancy,Most patients ignore
      such common age spots; however, others may have concern about their appearence,
      in which case the SKs have been surgicaly excised. In recent retrospective
      studies and case reports, SKs have rarely been found to have malignant
      characteristics. Although these studies are inconclusive, lesions that are
      inflamed, bleeding, ulcerated, or sufficiently irritated may require being
      biopsied to rule out melanoma or other malignancies.

PMID- 29566933
TI  - Retraction notice to "Bullous pemphigoid: Associations and management guidelines:
      Facts and controversies" [Clin. Dermatol. 31(2013) 400-412].

PMID- 29566934
TI  - Comparison of two dosing methods for immediate administration of tolvaptan in
      acute decompensated heart failure.
AB  - BACKGROUND: The clinical dosing method for tolvaptan in patients with acute heart
      failure (HF) is still unclear. We aimed to compare the differences in clinical
      effect between two dosing regimens: once-daily 7.5mg and twice-daily 3.75mg.
      METHODS: In this randomized trial, tolvaptan was administered within 12h from
      hospital admission. The primary outcome was the serial change in congestion
      scores measured every day from enrollment until dosing day 7. Outcomes including
      safety parameters were also evaluated. RESULTS: The subjects were assigned to
      either the once-daily 7.5mg dosing regimen (N=15) or the twice-daily 3.75mg
      dosing regimen (N=16). The time-course changes in body weight, serum sodium and
      creatinine levels, systolic blood pressure, daily urine output, and congestion
      scores were similar between the two groups. In the twice-daily 3.75mg dosing
      group, the serum sodium levels on days 3 and 4 were significantly (p<0.05)
      increased compared with those on day 1. The congestion scores significantly
      (p<0.05) decreased from day 2 to day 7 in both groups compared with those on day
      1. However, the difference in the serial change in the congestion scores did not
      reach statistical significance. CONCLUSIONS: Our present results suggest that the
      early administration of tolvaptan within 12h after hospital admission
      significantly improved congestion from the first day after administration by
      either dosing regimen, i.e. once-daily 7.5mg or twice-daily 3.75mg in patients
      with acute HF.

PMID- 29566935
TI  - Left atrial (dys)function in patients with light chain amyloidosis: A
      pathophysiological model with challenging prognostic significance.

PMID- 29566936
TI  - Council for the Advancement of Nursing Science Nursing Outlook.

PMID- 29566937
TI  - The mesenchymal and myeloid regulation of immunity: Power is nothing without
      control.

PMID- 29566938
TI  - Reducing waste in pediatric clinical research.
AB  - The importance of reducing waste and increasing value when conducting research
      has been emphasized by a series of articles published in the Lancet in 2014. A
      survey indicates that, one year later, these articles have not influenced how
      research is conducted. In this review, we explore four stages described by Moher
      et al. in research production that lead to waste. We show that all four stages
      including, questions relevant to users, appropriate design conduct and analysis,
      accessible full research, unbiased and usable reports, efficient research
      regulation and management of biomedical research are also producing an important
      waste in pediatric research. We conclude that methods to improve research quality
      and limit waste need to be implemented in pediatric research and recognized by
      authorities as a priority.

PMID- 29566939
TI  - [Bilateral mandibular nerve injury following mask ventilation: a case report].
AB  - BACKGROUND AND OBJECTIVES: Nerve injury following mask ventilation is a rare but
      serious anesthetic complication. The majority of reported cases are associated
      with excessive pressure applied to the face mask, long duration of mask
      ventilation, excessive digital pressure behind the mandible to relieve airway
      obstruction and pressure exerted by the plastic oropharyngeal airway. CASE
      REPORT: We present a case of bilateral mandibular nerve injury following mask
      ventilation with short duration, most likely due to a semi-silicone facemask with
      an over-inflated cushion. CONCLUSION: An over-inflated sealing cushion of a
      facemask may trigger difficult mask ventilation leading to mandibular nerve
      injury following mask ventilation. Alternative airway management techniques such
      as laryngeal mask airway should be considered when airway maintenance can only be
      achieved with strong pressure applied to the facemask and/or mandible.

PMID- 29566940
TI  - Breast carcinoma with osteoclast-like giant cells: A cytological-pathological
      correlation with a literature review.
AB  - Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease
      characterized by the infiltration of OGCs in the tumor; however, cytological
      aspects of this tumor type remain elusive. We examined the cytological features
      in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were
      histologically diagnosed with breast carcinoma with OGCs. We compared FNA and
      clinicopathological findings with results from the published literature.
      Histological assessment of the resected samples showed that all tumors exhibited
      a histological grade 1 phenotype with a predominant cribriform architecture. Four
      patients were estrogen receptor positive, and 1 patient showed a triple negative
      phenotype. All patients survived without tumor recurrence. In the FNA smears,
      tumor cells were arranged in loosely cohesive clusters, characterized by varying
      degrees of OGCs infiltration and rare formation of solid tumor nests.
      Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied
      by OGCs at the peripheral regions. In all patients, tumor cells were small
      without severe nuclear atypia. None of the patients showed significant background
      necrosis. In summary, cytological features of breast carcinoma with OGCs are
      characterized by loose aggregates of low grade tumor cells, the presence of OGCs,
      and the absence of necrosis, all of which were consistent with features reported
      previously. This peculiar form of breast tumors should be included in the
      differential diagnosis, when physicians encounter FNA findings including low
      grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.

PMID- 29566941
TI  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha is a
      predictor of lymph node metastasis and poor prognosis in human colorectal cancer.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) and PPARgamma
      coactivator-1alpha (PGC-1alpha) expression levels are correlated with clinical
      outcome in breast cancer. However, the potential biological and clinical
      significance of PPARgamma and PGC-1alpha in colorectal cancer remains unknown.
      Here we investigated PPARgamma and PGC-1alpha expression in colorectal cancer,
      and the associations of these expression levels with clinicopathological
      features. We also evaluated the roles of PPARgamma and PGC-1alpha as prognostic
      factors in colorectal cancer. We performed immunohistochemical analysis to
      investigate PPARgamma and PGC-1alpha expression in human colorectal cancer
      tissues and adjacent normal tissues from 108 primary colorectal cancer patients.
      We then examined how these expression levels correlated with clinicopathological
      features. Using the Kaplan-Meier method, we evaluated 3-year disease-free
      survival (DFS) and overall survival (OS) in patients with tumors expressing
      different levels of PPARgamma and PGC-1alpha. Our results revealed that PPARgamma
      expression was not significantly correlated with age at surgery, gender,
      differentiation, depth of infiltration, relapse, or TNM stage. Additionally, PGC
      1alpha expression was not significantly correlated with age at surgery,
      differentiation, depth of infiltration, relapse, or TNM stage. However, PGC
      1alpha expression was significantly correlated with nodal metastasis (p=0.020).
      Survival analysis demonstrated reduced OS in the PGC-1alpha-positive group
      compared to the PGC-1alpha-negative group (p=0.03). Our present findings suggest
      that PGC-1alpha may be useful for predicting nodal metastasis, and may represent
      a biomarker for poor prognosis in colorectal cancer.

PMID- 29566942
TI  - Intestinal isosporiasis in patients with acquired immunodeficiency syndrome
      (AIDS). Pathologic diagnosis in small intestinal mucosal biopsies.

PMID- 29566943
TI  - P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma
      in small biopsies and cytology specimens.
AB  - Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or
      cytological specimens based on cytomorphology; however in ambiguous cases
      diagnosis requires additional support by immunohistochemistry. While TP53 and RB1
      alterations with secondary overexpression of p16 are mainstay events in SCLC
      pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not
      yet been fully investigated. We examined the expression of p16, CD56,
      synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in
      a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary
      carcinoids and non-small cell lung carcinomas, and compared diagnostic
      performance of these markers in the diagnosis of SCLC. P16 was positive in 95 of
      101 SCLCs, and displayed highest diagnostic sensitivity of ~94%. Composite
      biomarkers CD56+p16+TTF1 and CD56+p16+SYP were both able to detect correctly all
      SCLC cases. Importantly, three (~3%) SCLC cases completely negative for all
      conventional markers displayed diffuse positivity for p16. CD56 and p16
      demonstrated highest concordance between paired small biopsy and cytology
      specimens. 50% of squamous cell carcinomas, ~41% of adenocarcinoma/NSCLC-favour
      adenocarcinoma cases, and ~93% of extrapulmonary small cell carcinomas also
      showed p16-positivity. Combination of CD56, p16 and TTF1 produced diagnostic
      classifier that outperformed best single marker CD56 in differential diagnosis
      between SCLC and NSCLC. In conclusion, in the appropriate morphological context
      p16 represents a useful supplementary marker for diagnosis of SCLC, even in cases
      where only cytological material is available.

PMID- 29566944
TI  - Hodgkin lymphoma with an interfollicular growth pattern: A clinicopathologic
      study of 8 cases.
AB  - Classic Hodgkin lymphoma (CHL) has four subtypes. Different morphologic
      variations can be seen in lymph nodes involved by CHL. Primary interfollicular
      (IF) involvement is not considered a separate subtype but an unusual
      diagnostically challenging morphologic variant. Our aim was to study the
      prevalence of IF growth pattern and coexistence of other morphologic variants in
      lymph nodes involved by CHL, to investigate the diagnostic challenges and
      clinical importance of this growth pattern, and to find helpful histologic clues
      in cases with subtle morphologic features to help avoid misinterpretation and
      missed diagnosis. We performed a retrospective review study over 10years. We
      searched for diagnosed cases of nodal CHL. We retrieved and reviewed cases of CHL
      with IF involvement. The clinical and pathologic features of each case were
      collected and compared. We found 103 cases of CHLs. Eight cases (7.8%)
      demonstrated IF growth patterns. The age range was between 3 and 48years with an
      average age of 26years. The male to female ratio was 7:1. Six cases were mixed
      cellularity HLs. Three cases had associated epithelioid granulomas, one had
      follicular involvement and one had an associated. HHV-8 negative plasma cell rich
      Castleman disease. One case was initially missed as benign follicular
      hyperplasia, one case was referred as CD and three cases were initially suspected
      as HL. IF growth pattern in nodal CHLs can be missed because it can be mild and
      focal with subtle morphologic features. The presence of epithelioid histiocytes,
      eosinophils and other coexistent morphologic variants are helpful histologic
      clues. In doubtful cases, immunohistochemistry study is essential. The majority
      were early stage cervical node MCHLs in young adults and children. Pathologists
      should be aware of this possibility when examining reactive lymph nodes. The
      clinical significance is limited and needs further validation by larger studies.

PMID- 29566945
TI  - Intra-surgical total and re-constructible pathological prostate examination for
      safer margins and nerve preservation (Istanbul preserve).
AB  - PURPOSE: To demonstrate a novel frozen section analysis technique during robot
      assisted radical prostatectomy with 2 distinct advantages: evaluation of the
      entire circumference and easier reconstruction for whole mount evaluation.
      MATERIAL AND METHODS: Istanbul Preserve was performed on patients who underwent
      robotic prostatectomy with nerve sparing between 10/2014 and 7/2016. Gland was
      sectioned at 3-4mm intervals from apex to bladder neck. Entire tissue
      representing margins (except for the most anterior portion) was circumferentially
      excised and microscopically analyzed. In margin positivity, approach was
      individualized based on extent of positive margin and Gleason pattern. A matched
      cohort was established for comparison. Retrospective analysis of a prospectively
      maintained database was performed. Impact of FSA on PSM rate was primarily
      assessed. RESULTS: Data on 170 patients was analyzed. Positive surgical margin
      was reported in 56(33%) on frozen section. Neurovascular bundle was partially or
      totally resected in 79% and 18%. Conversion of positive margin to negative was
      achieved in 85%. Overall positive margin rate decreased from 22.5% to 7.5%. Nerve
      sparing increased from 87% to 93%. Location of positive margin at frozen was at
      the neurovascular bundle area in 39%; thus Istanbul Preserve detected 61%
      additional margin positivity compared to other techniques. Reconstruction for
      whole mount was easy. CONCLUSION: Istanbul Preserve is a novel technique for
      intraoperative FSA during RARP allowing for microscopic examination of the entire
      prostate for margin status and easy re-construction for whole mount examination.
      It guarantees safer margins together with increased rate of nerve sparing.

PMID- 29566946
TI  - High cytoplasmic HuR expression is associated with advanced pT stage, high grade
      and increased microvessel density in urothelial bladder carcinoma.
AB  - PURPOSE: HuR (human antigen R) protein is a RNA binding protein that stabilizes
      the mRNA and controls the translation of genes involved in cell proliferation,
      differentiation, and carcinogenesis. Overexpression of HuR was reported in a
      variety of cancers, however its clinical significance in urothelial bladder
      cancer (UBC) is still unknown. Our aim is to investigate the association between
      HuR expression and selected histopathological factors, such as tumor grade, pT
      stage, regional lymph nodes status and microvessel density (MVD). METHODS: We
      studied expression of HuR protein in 119 patients with UBC in stages pTis and pTa
      pT4 using immunohistochemistry (IHC). Tumor MVD was evaluated
      immunohistochemically using anti-CD31 antibody. RESULTS: We observed no
      association between nuclear HuR immunoreactivity and tumor grade, stage or MVD.
      We found a significant association between cytoplasmic HuR positivity and high
      tumor grade, pT stage and MVD (p<0,001). We also observed significantly higher
      MVD values in cases with positive cytoplasmic HuR expression (p<0,001). No
      association between HuR immunoreactivity and lymph nodes status was found.
      CONCLUSIONS: Our results may suggest that HuR is involved in the process of
      acquiring malignant histopathological features and ability to invade the
      muscularis propria by UBC cells. Considering frequent difficulties in diagnosing
      UBC in specimens obtained from transurethral tumor resection and the risk of
      understaging, cytoplasmic HuR expression would suggest an advanced disease and
      necessitate serial sectioning of the specimen in search of muscle invasion.
      Association between HuR expression and MVD could suggest HuR involvement in the
      process of angiogenesis in UBC.

PMID- 29566947
TI  - Intraoperative sentinel lymph node evaluation: Optimizing surgical pathology
      practices in an era of changing clinical management.
AB  - Axillary lymph node status is an independent prognostic indicator in breast
      cancer. Intraoperative identification of metastatic carcinoma in sentinel lymph
      nodes may allow for concurrent axillary lymph node dissection at the time of
      primary tumor excision. A retrospective review of patients undergoing primary
      breast cancer excision with sentinel lymph node sampling was performed.
      Sensitivity and specificity of imprint cytology (touch prep) with and without the
      incorporation of gross evaluation was determined using permanent section results
      as the gold standard. Five hundred sixteen lymph nodes were analyzed by imprint
      cytology in 213 patients, and 203 lymph nodes were analyzed in 74 patients
      incorporating gross examination. Sensitivity and specificity for the detection of
      macrometastases by touch prep alone were 60% and 99% respectively with 4 patients
      undergoing same-day axillary dissection for only micrometastatic disease. False
      negative causes included lack of transfer of malignant cells in 8 cases and
      misinterpretation of tumor cells in 6 cases. Incorporating gross examination in
      the modified protocol resulted in reduced sensitivity of 38%, but achieved the
      desired 100% specificity and positive predictive value. Imprint cytology alone
      did not reliably distinguish between micro- and macrometastatic disease. Gross
      assessment combined with imprint cytology allows for improved assessment of
      volume of axillary disease, but is an insensitive technique.

PMID- 29566948
TI  - A retrospective analysis of paediatric lymphomas at Chris Hani Baragwanath
      Academic Hospital in Soweto, South Africa.

PMID- 29566949
TI  - Secretory carcinoma of the parotid with adenoid cystic carcinoma cytological
      pattern: A cytological-pathological correlation with literature review.
AB  - Secretory carcinoma (SC) is a rare low-grade malignant tumor, defined by ETV6
      NTRK3 fusion, identifiable by FISH. We describe a case in a 58-year-old male with
      a painless slowly growing 16mm palpable mass within left superficial parotid. FNA
      of the mass showed highly cellular specimen with moderate to large pleomorphic
      cells with round to ovoid nuclei with vesicular chromatin and distinct nucleoli.
      Cells had moderate to large amounts of vacuolated cytoplasm. Abundant globular
      metachromatic material, resembling that of adenoid cystic carcinoma, was noted.
      This material was seen extracellularly and intracytoplasmic, and stained magenta
      on Diff-Quik and blue-green on Papanicolaou-stained slides. The tumor cells on a
      cell block preparation were positive for Mammaglobin and S-100. PAS stain
      highlighted extracellular and intracytoplasmic secretions. FNA diagnosis was
      "Positive for Malignancy. Morphologic features most compatible with Mammary
      Analogue Secretory Carcinoma". ETV6 FISH studies as well as histologic
      examination of excised tumor confirmed the diagnosis. Finding the globular
      metachromatic material in SC, that is generally seen in adenoid cystic carcinoma,
      broadens a cytological differential diagnosis of both entities. Cytological
      differential diagnosis, clinical, histological, immunohistochemical, and
      molecular features of secretory carcinomas are discussed in this study.

PMID- 29566950
TI  - Biphenotypic sinonasal sarcoma: A series of six cases with evaluation of role of
      beta-catenin immunohistochemistry in differential diagnosis.
AB  - INTRODUCTION: Biphenotypic sinonasal sarcoma (BSNS) is a recently described
      mesenchymal tumor exclusive to the sinonasal region. It is a low grade sarcoma,
      displaying evidence of myogenic and neural differentiation. Role of beta-catenin
      immunohistochemistry in distinguishing it from its morphological mimics is not
      well-established. We conducted this study to identify cases of BSNS from our
      archives, and to examine immunopositivity for beta-catenin in them as well as in
      its close differential diagnosis. METHODS: All cases of nasal cavity and
      paranasal sinus mesenchymal neoplasms were identified. Histopathological features
      were reviewed. Cases showing smooth muscle actin (SMA) and S-100
      immunopositivity, and typical morphology were reclassified as BSNS. beta-catenin
      immunoexpression was assessed. RESULTS: Twenty-one mesenchymal tumors, including
      12 sinonasal hemangiopericytoma (SNHPC), five solitary fibrous tumors (SFT),
      three BSNS, and one synovial sarcoma were identified. Three SNHPC cases were
      reclassified as BSNS. BSNS patients included one male and five females, with mean
      age of 51years. Five BSNS cases (83.3%) showed nuclear beta-catenin
      immunopositivity. SNHPC cases also were beta-catenin positive (60%). CONCLUSION:
      BSNS is a rare sinonasal neoplasm, frequently misdiagnosed as SNHPC and SFT. beta
      catenin immunopositivity is seen in majority of cases, indicating a role in
      pathogenesis. However, due to positivity in other tumors like SNHPC, it has
      limited role in differential diagnosis.

PMID- 29566951
TI  - Composition of the immune microenvironment differs between carcinomas metastatic
      to the lungs and primary lung carcinomas.
AB  - Lungs are among the most common sites for development of both primary and
      metastatic carcinomas. Tumor cells expression (TC) of PD-L1 is an important
      predictor of the of response to immune check-point inhibition in NSCLC, while the
      composition of the immune cells (IC) in the tumor microenvironment including PD
      L1+ cells is believed to predict responses in tumors of some other primary sites.
      Total mutational load (TML) and microsatellite instability (MSI) also play a role
      in response to the immune checkpoint blockade. We investigated immune
      microenvironment characteristics (PD-1, PD-L1, CD8) of 257 lung biopsies
      including 81 primary (NSCLC) and 176 metastatic tumors to the lungs. TML and MSI
      were calculated from massively parallel sequencing (592-gene panel). TC
      expression of PD-L1 was more common in NSCLC than in metastatic carcinomas (28%
      vs. 10%, p=0.009), while PD-L1-positive IC were present at relevant percentages
      (1-5%) exclusively in metastatic carcinomas (31% IC positive vs. 0%, p<0.001).
      Metastatic carcinomas carried significantly lower TML in comparison with the
      NSCLCs (6.6 mutations on average vs. 10, p=0.01). All primary NSCLC were
      microsatellite stable, and only 2 metastatic carcinomas exhibited MSI-H status.
      The number of PD-1+ and CD8+ tumor infiltrating lymphocytes did not differ
      significantly between the primary and metastatic carcinomas. Our study revealed
      significant differences in tumor immune microenvironment (PD-L1 in IC and TC),
      and its relationship to TML between NSCLC and metastatic cancers. These
      differences could determine the choice of a predictive biomarker test and
      subsequently effect(s) of the immune therapy treatments in various advanced
      cancers.

PMID- 29566953
TI  - Three-stage post-oncological reconstruction of the scalp using a dermal-assisted
      skin graft, adipose tissue graft and follicular graft: A clinical case.

PMID- 29566954
TI  - Skin-reducing oncoplasty: A new concept and classification in breast cancer
      surgery.
AB  - BACKGROUND AND OBJECTIVES: Breast-conserving surgery and skin-sparing mastectomy
      are nowadays widely accepted as the standard of care in selected patients with
      early breast cancer. After an accurate review of the literature, it appeared that
      no ordered list of the numerous techniques described for conservative breast
      surgery has been established so far. The aim of this study was to develop a
      simple classification of the different skin incision patterns that may be used in
      breast surgery. METHODS: A systematic review of the English literature was
      conducted using the PubMed database to identify all the articles reporting breast
      conserving surgery and skin-sparring mastectomy techniques up to the 31st of
      December 2016. RESULTS: Among the 1426 titles identified, 230 were selected for
      review. Based on the reviewed papers, the skin-reducing oncoplasty incision
      pattern (SROIP) classification was elaborated. CONCLUSIONS: Breast cancer surgery
      should nowadays optimise aesthetic outcomes by improving the final breast shape,
      volume and scar location. This may be achieved using different procedures that we
      grouped together under the term skin-reducing oncoplasty (SRO). Depending on the
      breast cancer location, the SROIP classification helps in the choice of the best
      technique to be used.

PMID- 29566955
TI  - [Paracommissural cleft of the lower lip: Therapeutic strategy].
AB  - We report the first case described in the literature of lateral, paracommissural
      cleft of the lower lip in a 2-year-old child. This anomaly caused labial
      incompetence requiring surgical correction. Different surgical techniques have
      been described for the treatment of the cleft of the upper lip. We studied each
      of them, analyzed the advantages and disadvantages of these techniques by
      inverting them and adapting them for the lower lip. We opted for the double "Z"
      plasty of Malek because the difference in height between the cleft side and the
      healthy side was important. In addition, this plasty hides part of the scar in
      the labiomental groove. The functional and aesthetic result at 6 months after
      surgery is satisfactory.

PMID- 29566956
TI  - Transcultural adaptation and psychometric properties of Spanish version of
      Pregnancy Physical Activity Questionnaire: the PregnActive project.
AB  - OBJECTIVE: To transculturally adapt the Spanish version of Pregnancy Physical
      Activity Questionnaire (PPAQ) analyzing its psychometric properties. METHODS: The
      PPAQ was transculturally adapted into Spanish. Test-retest reliability was
      evaluated in a subsample of 109 pregnant women. The validity was evaluated in a
      sample of 208 pregnant women who answered the questionnaire and wore the multi
      sensor monitor for 7 valid days. The reliability (intraclass correlation
      coefficient), concordance (concordance correlation coefficient), correlation
      (Pearson correlation coefficient), agreement (Bland-Altman plots) and relative
      activity levels (Jonckheere-Terpstra test) between both administrations and
      methods were examined. RESULTS: Intraclass correlation coefficients between both
      administrations were good for all categories except transportation. A low but
      significant correlation was found for total activity (light and above) whereas no
      correlation was found for other intensities between both methods. Relative
      activity levels analysis showed a significant linear trend for increased total
      activity between both methods. CONCLUSIONS: Spanish version of PPAQ is a brief
      and easily interpretable questionnaire with good reliability and ability to rank
      individuals, and poor validity compared with multi-sensor monitor. The use of
      PPAQ provides information of pregnancy-specific activities in order to establish
      physical activity levels of pregnant women and adapt health promotion
      interventions.

PMID- 29566957
TI  - Negative Multiparametric Magnetic Resonance Imaging for Prostate Cancer: What's
      Next?
AB  - BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) of the prostate
      has excellent sensitivity in detecting clinically significant prostate cancer
      (csPCa). Nevertheless, the clinical utility of negative mpMRI (nMRI) is less
      clear. OBJECTIVE: To assess outcomes of men with nMRI and clinical follow-up
      after 7 yr of activity at a reference center. DESIGN, SETTING, AND PARTICIPANTS:
      All mpMRI performed from January 2010 to May 2015 were reviewed. We selected all
      patients with nMRI and divided them in group A (naive patients) and group B
      (previous negative biopsy). All patients without a diagnosis of PCa had a minimum
      follow-up of 2 yr and at least two consecutive nMRI. Patients with positive mpMRI
      were also identified to assess their biopsy outcomes. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: A Kaplan-Meier analysis was performed to assess both any
      grade PCa and csPCa diagnosis-free survival probabilities. Univariable and
      multivariable Cox regression models were fitted to identify predictors of csPCa
      diagnosis. RESULTS AND LIMITATIONS: We identified 1545 men with nMRI, and 1255 of
      them satisfied the inclusion criteria; 659 belonged to group A and 596 to group
      B. Any-grade PCa and csPCa diagnosis-free survival probabilities after 2 yr of
      follow-up were 94% and 95%, respectively, in group A; in group B, they were 96%.
      After 48 mo of follow-up, any-grade PCa diagnosis-free survival probability was
      84% in group A and 96% in group B (log rank p<0.001). Diagnosis-free survival
      probability for csPCa was unchanged after 48 mo of follow-up. On multivariable
      Cox regression analysis, increasing age (p=0.005) was an independent predictor of
      lower csPCa diagnosis probability, while increasing prostate-specific antigen
      (PSA) and PSA density (<0.001) independently predicted higher csPCa diagnosis
      probability. The prevalence of and positive predictive value for csPCa were 31.6%
      and 45.5%, respectively. Limitations include limited follow-up and the inability
      to calculate true csPCa prevalence in the study population. CONCLUSIONS: mpMRI is
      highly reliable to exclude csPCa. Nevertheless, systematic biopsy should be
      recommended even after nMRI, especially in younger patients with high or raising
      PSA levels. PATIENT SUMMARY: It is a matter of debate whether patients with
      negative multiparametric magnetic resonance imaging (mpMRI) of the prostate could
      obviate the need to perform a systematic biopsy. In this report, we looked at the
      outcomes of patients with negative mpMRI and midterm clinical follow-up at a
      reference center. We found mpMRI to be highly reliable to exclude significant
      prostate cancer; nonetheless, systematic biopsy must still be recommended after
      negative mpMRI in patients with high clinical suspicion of prostate cancer.

PMID- 29566958
TI  - Cell-free DNA in Advanced Prostate Cancer: A Biomarker Revolution Under Way?

PMID- 29566959
TI  - Impact of missing data strategies in studies of parental employment and health:
      Missing items, missing waves, and missing mothers.
AB  - BACKGROUND: Understanding the long-term health effects of employment - a major
      social determinant - on population health is best understood via longitudinal
      cohort studies, yet missing data (attrition, item non-response) remain a
      ubiquitous challenge. Additionally, and unique to the work-family context, is the
      intermittent participation of parents, particularly mothers, in employment,
      yielding 'incomplete' data. Missing data are patterned by gender and social
      circumstances, and the extent and nature of resulting biases are unknown. METHOD:
      This study investigates how estimates of the association between work-family
      conflict and mental health depend on the use of four different approaches to
      missing data treatment, each of which allows for progressive inclusion of more
      cases in the analyses. We used 5 waves of data from 4983 mothers participating in
      the Longitudinal Study of Australian Children. RESULTS: Only 23% had completely
      observed work-family conflict data across all waves. Participants with and
      without missing data differed such that complete cases were the most advantaged
      group. Comparison of the missing data treatments indicate the expected narrowing
      of confidence intervals when more sample were included. However, impact on the
      estimated strength of association varied by level of exposure: At the lower
      levels of work-family conflict, estimates strengthened (were larger); at higher
      levels they weakened (were smaller). CONCLUSIONS: Our results suggest that
      inadequate handling of missing data in extant longitudinal studies of work-family
      conflict and mental health may have misestimated the adverse effects of work
      family conflict, particularly for mothers. Considerable caution should be
      exercised in interpreting analyses that fail to explore and account for biases
      arising from missing data.

PMID- 29566960
TI  - Relationship transitions and change in health behavior: A four-phase, twelve-year
      longitudinal study.
AB  - RATIONALE: Extensive scientific evidence shows an association between involvement
      in social relationships and healthy lifestyle. Prospective studies with many
      participants and long follow-ups are needed to study the dynamics and change in
      social factors within individuals over time. OBJECTIVE: Our aim was to determine
      whether a change in relationship status (single, married, divorced, widow,
      cohabiting) is followed by a change in health behavior (smoking, alcohol
      consumption, physical activity, and body mass index). METHODS: We used data from
      81,925 healthy adults participating in the prospective longitudinal Finnish
      Public Sector Study in the period 2000-2013. We analyzed 327,700 person
      observations from four data collection phases. Missing data were multiply
      imputed. A within-individual methodology was used to minimize the possibility of
      selection effects affecting the interpretation. RESULTS: All four health
      behaviors showed associations with relationship status. The effects were very
      similar and in the same direction in women and men, although there were gender
      differences in the magnitudes of the effects. The end of a relationship was
      followed by a decrease in body mass index, increased odds of being a smoker,
      increase in physical activity, and increase in alcohol consumption (widowed men).
      The effects were reverse when forming a new relationship. CONCLUSION: A change in
      relationship status is associated with a change in health behavior. The
      association is not explained by socioeconomic status, subjective health status,
      or anxiety level. People leaving or losing a relationship are at increased risk
      of unhealthy behavior (smoking and alcohol consumption), but at the same time
      they have a lower BMI and show higher physical activity compared to the time they
      were in a relationship. It is not clear if the cumulative health effect of these
      health behavior changes is positive or negative.

PMID- 29566961
TI  - Diagnosis and treatment of 34 cases of congenital tracheobronchial cartilage
      remnants of esophagus.
AB  - PURPOSE: To describe the diagnosis and treatment of 34 cases of congenital
      tracheobronchial cartilage remnants of esophagus. METHODS: The diagnosis and
      treatment of 34 cases of congenital tracheobronchial cartilage remnants of
      esophagus were analyzed retrospectively in our hospital. RESULTS: Congenital
      tracheobronchial cartilage remnants of esophagus could be specifically diagnosed
      by clinical situation and esophageal barium meal examination. The anterior wall
      of the esophagus was cut longitudinally with the posterior wall of the esophagus
      preserved. And the cartilage was removed and the open anterior wall of the
      esophagus was sutured horizontally with full layer. In our study, 34 patients who
      underwent the operation had a satisfactory outcome. However, one patient
      underwent submucosal cartilage stripping, which resulted in a complication
      involving fistulae from the esophagus to the abdominal cavity that were healed
      after gastrostomy and nutritional support. CONCLUSION: Congenital
      tracheobronchial cartilage remnants of esophagus caused symptoms when the infants
      were started on adjunct foods. Vomiting the food without gastric fluid and bile
      was the leading clinical manifestation. Distinguishing signs on esophageal barium
      contrast could be used as preoperative diagnosis evidence. Surgically removing
      the cartilage and horizontally suturing the esophagus provides a reliable
      outcome. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Retrospective study.

PMID- 29566962
TI  - Norton scale and vital prognosis.

PMID- 29566963
TI  - Analysis of the relationship between interleukin polymorphisms within miRNA
      binding regions and alcoholic liver disease.
AB  - INTRODUCTION: Alcohol consumption promotes inflammation through the Toll-like
      receptor 4 (TLR4)/nuclear factor (NF)-?B pathway, leading to organic damage. Some
      micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating
      TLR4/NF-?B pathway mediators, like interleukins (ILs). Thus, polymorphisms within
      IL genes located near miRNA binding sites could modify the risk of ethanol
      induced damage. The present study analyzed potential relationships between
      alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16
      5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143)
      polymorphisms. PATIENTS AND METHODS: The study included 301 male alcoholic
      patients and 156 male healthy volunteers. Polymorphisms were genotyped using
      TaqMan(r) PCR assays for allelic discrimination. Allele and genotype frequencies
      were compared between groups. Logistic regression analysis was performed to
      analyze the inheritance model. RESULTS: Analysis of the IL1R1 (rs3917328)
      polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes)
      was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042).
      However, multivariable logistic regression analyses did not yield a significant
      result. No differences between groups were found for other analyzed
      polymorphisms. CONCLUSIONS: Our study describes, for the first time, the expected
      frequencies of certain polymorphisms within miRNA-binding sites in alcoholic
      patients with and without ALD. Further studies should be developed to clarify the
      potential relevance of these polymorphisms in alcoholism and ALD development.

PMID- 29566964
TI  - An atypical cause of pulmonary hypertension in the elderly.

PMID- 29566965
TI  - Predicting eventual development of lupus nephritis at the time of diagnosis of
      systemic lupus erythematosus.
AB  - OBJECTIVES: To investigate factors predictive of future lupus nephritis
      development when systemic lupus erythematosus (SLE) is diagnosed. METHODS:
      Patients with newly diagnosed SLE without renal manifestations were followed for
      development of lupus nephritis, comparing findings at baseline between those who
      did or did not develop nephritis. Albumin-to-globulin ratio (AGR) was calculated
      as albumin/(total protein-albumin). Cox proportional hazard model was used to
      identify predictors of lupus nephritis. RESULTS: Of 278 patients, 241 did not and
      37 did develop lupus nephritis during follow-up. On univariate analysis, young
      age, low C3, low C4, high anti-dsDNA titre, anti-Sm antibody, anti-RNP antibody
      and low AGR were associated with a higher risk of lupus nephritis. On
      multivariate analysis, factors predictive of nephritis were age [adjusted hazard
      ratio (aHR) 0.928, 95% confidence interval (CI): 0.895-0.961, p < 0.001], C3 (aHR
      0.977, 95% CI: 0.966-0.989, p < 0.001), anti-dsDNA titre (aHR 1.004, 95% CI:
      1.000-1.007, p = 0.026) and anti-Sm antibody (aHR 2.097, 95% CI: 1.040-4.229, p =
      0.038). In particular, a low AGR (aHR 4.972, 95% CI: 2.394-10.326, p < 0.001) was
      strongly associated with an increased risk of future lupus nephritis development.
      CONCLUSION: Young age, low C3, high anti-dsDNA titre and presence of anti-Sm
      antibody at diagnosis of SLE were associated with a risk of future lupus
      nephritis, but the hazard was greatest with a low AGR value, suggesting that a
      greater proportion of immunoglobulin relative to total protein is associated with
      the development of nephritis.

PMID- 29566966
TI  - Considerations for the definition of remission criteria in psoriatic arthritis.
AB  - OBJECTIVES: Psoriatic arthritis (PsA) is an autoimmune disease that can cause
      progressive structural damage of the joints and irreversible disability. The
      potentially achievable results of biologic therapy for PsA has led to the view
      that disease remission should be the goal of treatment. However, the
      heterogeneity of disease manifestations and need for validated outcome measures
      makes defining remission in PsA challenging. This article evaluates proposed
      criteria for defining remission in PsA and discusses how these criteria can be
      applied in clinical practice. METHODS: A primary literature search was conducted
      in PubMed to identify articles discussing potential PsA treatment goals or
      targets, including minimal disease activity. English-language publications from
      the last 10 years were included in this assessment. RESULTS: There are 5 clinical
      domains in PsA that must be considered when evaluating remission: synovitis,
      enthesitis, dactylitis, spondylitis, and psoriasis/nail psoriasis. Due to
      variability in the completeness of remission and time to achieve remission with
      different therapies between these domains, remission should be measured
      clinically through a combination of objective measures, or a composite assessment
      tool. Composite measures are more efficient than unidimensional instruments in
      measuring remission, but remission rates differ between the available composite
      indices. CONCLUSION: Although the concept of remission as a treatment goal in PsA
      is gaining acceptance among rheumatologists, further work is necessary to develop
      a broadly acceptable definition of remission.

PMID- 29566967
TI  - Serum urate as surrogate endpoint for flares in people with gout: A systematic
      review and meta-regression analysis.
AB  - OBJECTIVES: The primary efficacy outcome in trials of urate lowering therapy
      (ULT) for gout is serum urate (SU). The aim of this study was to examine the
      strength of the relationship between SU and patient-important outcomes to
      determine whether SU is an adequate surrogate endpoint for clinical trials.
      METHODS: Multiple databases through October 2017 were searched. Randomized
      controlled trials comparing any ULT in people with gout with any control or
      placebo, >=three months duration were included. Open label extension (OLE) trial
      data were included in secondary analyses. Standardized data elements were
      extracted independently by two reviewers. RESULTS: Ten RCTs and 3 OLE studies
      were identified. From the RCTs (maximum duration 24 months) meta-regression did
      not reveal an association between the relative risk of a gout flare and the
      difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In
      a post hoc analysis, the ratio of the time in months at which the proportion of
      individuals having a flare was reported/time in months at which the proportion of
      individuals with SU < 6mg/dL was reported was calculated and studies where the
      ratio was <2 were excluded. Using the remaining 6 studies there was an
      association between proportion of individuals achieving SU < 6mg/dL and gout
      flares (over patient years). Duration of ULT was inversely associated with the
      proportion of patients experiencing a flare. Study duration and variability in
      reporting of outcomes limited the analysis. Observational studies supported the
      trend of fewer flares in those with lower SU. CONCLUSIONS: Based on aggregate
      clinical trial-level data an association between SU and gout flare could not be
      confirmed. However, based on observational ecological study design data-including
      longer duration extension studies-SU < 6mg/dL was associated with reduced gout
      flares.

PMID- 29566968
TI  - Whole-body computed tomography as a factor associated with lower mortality in
      severe geriatric trauma with thoracic-abdominal-pelvic injury.
AB  - OBJECTIVE: To determine the relationship between the use of whole-body computed
      tomography (WB-CT) and hospital mortality in elderly patients with thoracic
      abdominal-pelvic injury requiring admission to an intensive care unit. PATIENTS
      AND METHOD: An observational, descriptive and retrospective study was conducted
      on 140 patients aged 65 years and older admitted to the intensive care unit after
      a thoracic-abdominal-pelvic injury. Two groups were established, depending on
      whether a WB-CT was performed as a routine part of the study or the diagnosis was
      established by conventional radiography or ultrasound. A comparative analysis was
      performed on both groups, as well as an analysis of mortality through logistic
      regression. RESULTS: The mean age of the patients was 75.16+/-8.89 years. The
      mean score on the APACHE II scale was 16.25+/-8.4 points, and on the Injury
      Severity Score scale, 22.38+/-15.45 points. WB-CT was performed on 102 patients
      (72.9%). In these patients, there was a lower mortality rate (15.7 vs. 52.6%,
      P?.001), a lower need for mechanical ventilation (47.1 vs. 65.8%, P=.049), and a
      lower score on the APACHE II scale (14.75+/-7.19 vs. 20.26+/-10.06 points,
      P=.003). The multivariate analysis showed a lower mortality in the patients in
      whom WB-CT was performed, with an OR of 0.21 (95% CI 0.07-0.68; (P=.010), after
      adjusting for the APACHE II and ISS scores. CONCLUSIONS: Performing a WB-CT scan
      as part of the trauma study could improve the management of elderly patients with
      thoracic-abdominal-pelvic involvement admitted to the intensive care unit.

PMID- 29566969
TI  - Spontaneous Regression of an Infectious Pulmonary Artery Pseudoaneurysm.

PMID- 29566970
TI  - Success in Optional Vena Cava Filter Retrieval. An Analysis of 246 Patients.
AB  - OBJECTIVE: This study assessed vena cava filter (VCF) retrieval rates and factors
      associated with retrieval failure in a single center cohort. METHODS: We
      conducted an observational retrospective cohort study. The primary endpoint was
      the percentage of patients whose VCF was retrieved. We performed logistic
      regression to identify variables associated with retrieval failure. RESULTS:
      During the study period, 246 patients received a VCF and met the eligibility
      requirements to be included in the study; 151 (61%) patients received a VCF due
      to contraindication to anticoagulation, 69 (28%) patients had venous
      thromboembolism (VTE) and a high risk of recurrence, and 26 (11%) patients
      received a filter due to recurrent VTE while on anticoagulant therapy. Of 236
      patients who survived the first month after diagnosis of VTE, VCF was retrieved
      in 96%. Retrieval rates were significantly lower for patients with recurrent VTE
      while on anticoagulation, compared with patients with contraindication to
      anticoagulation or patients with a high risk of recurrence (79% vs. 97% vs. 100%,
      respectively; P<0.01). Mean time to retrieval attempt was significantly
      associated with retrieval failure (137.8 +/- 65.3 vs. 46.3 +/- 123.1 days,
      P<0.001). CONCLUSIONS: In this single center study, VCF retrieval success was
      96%. A delay in the attempt to retrieve the VCF correlated significantly with
      retrieval failure.

PMID- 29566971
TI  - The MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease
      Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up.
AB  - The general aim of this study is to create a cohort of asthma patients with
      varying grades of severity in order to gain greater insight into the mechanisms
      underlying the genesis and course of this disease. The specific objectives focus
      on various studies, including imaging, lung function, inflammation, and bronchial
      hyperresponsiveness, to determine the relevant events that characterize the
      asthma population, the long-term parameters that can determine changes in the
      severity of patients, and the treatments that influence disease progression. The
      study will also seek to identify the causes of exacerbations and how this affects
      the course of the disease. Patients will be contacted via the outpatient clinics
      of the 8 participating institutions under the auspices of the Spanish Respiratory
      Diseases Networking System (CIBER). In the inclusion visit, a standardized
      clinical history will be obtained, a clinical examination, including blood
      pressure, body mass index, complete respiratory function tests, and FENO will be
      performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality
      of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and
      the Hospital Anxiety and Depression scale (HADS) will be administered. A specific
      electronic database has been designed for data collection. Exhaled breath
      condensate, urine and blood samples will also be collected. Non-specific
      bronchial hyperresponsiveness testing with methacholine will be performed and an
      induced sputum sample will be collected at the beginning of the study and every
      24 months. A skin prick test for airborne allergens and a chest CT will be
      performed at the beginning of the study and repeated every 5 years.

PMID- 29566972
TI  - Statin add-on therapy for schizophrenia: Is the effect the same for clozapine?

PMID- 29566973
TI  - Immunology of oligodendrocyte precursor cells in vivo and in vitro.
AB  - Remyelination following myelin/oligodendrocyte injury in the central nervous
      system (CNS) is dependent on oligodendrocyte progenitor cells (OPCs) migrating
      into lesion sites, differentiating into myelinating oligodendrocytes (OLs), and
      ensheathing axons. Experimental models indicate that robust OPC-dependent
      remyelination can occur in the CNS; in contrast, histologic and imaging studies
      of lesions in the human disease multiple sclerosis (MS) indicate the variable
      extent of this response, which is particularly limited in more chronic MS
      lesions. Immune-mediated mechanisms can contribute either positively or
      negatively to the presence and functional responses of OPCs. This review
      addresses i) the molecular signature and functional properties of OPCs in the
      adult human brain; ii) the status (presence and function) of OPCs in MS lesions;
      iii) experimental models and in vitro data highlighting the contribution of
      adaptive and innate immune constituents to OPC injury and remyelination; and iv)
      effects of MS-directed immunotherapies on OPCs, either directly or indirectly via
      effects on specific immune constituents.

PMID- 29566975
TI  - Break the "wall" and become creative: Enacting embodied metaphors in virtual
      reality.
AB  - This study investigated whether the experience of "breaking the walls", the
      embodiment of the metaphor "breaking the rules", could enhance creative
      performance. The virtual reality technology was used to simulate the scenario
      where participants could "break the walls" while walking in a corridor.
      Participants were asked to solve the creativity-demanding problems (ie.,
      alternative uses tasks, AUT) in either the "break" condition in which they had to
      break the walls to move forward in VR, or the "no-break" condition where no
      barrier walls would appear. Results showed higher AUT originality and AUT fluency
      in the "break" condition than in the "no-break" condition. Moreover, the effects
      of "breaking the walls" on AUT originality were fully mediated by cognitive
      flexibility and persistence. These findings may indicate that enacting metaphors
      such as "breaking the rules" contribute to creative performance. The enhanced
      cognitive flexibility and persistence may account for the benefits.

PMID- 29566974
TI  - Donor human milk and risk of surgical necrotizing enterocolitis: A meta-analysis.
AB  - BACKGROUND & AIM: The prevention of necrotizing enterocolitis (NEC) is a primary
      goal in the care of preterm and low birth-weight infants. Donor-banked milk (DM)
      feeding has been reported to have a protective effect towards NEC with respect to
      formula-feeding. All the meta-analysis published so far, have been focused on the
      protective effect of DM on the overall risk of NEC, none of them focused on the
      risk of the most severe cases on NEC only, that are those requiring surgery. We
      conducted a meta-analysis of available evidences on the risk of developing
      surgical cases of NEC in DM-fed preterm and/or low birth weight infants with
      respect to those formula-fed. METHODS: A search for articles published between
      January 1960 and January 2018 and addressing the association between DM and
      surgical NEC was conducted via PubMed, Embase and Cochrane database. We included
      randomized controlled clinical trials, reporting primary data and involving
      preterm and/or low birth weight infants fed with preterm formula compared to DM,
      both as sole diet or complementing own mother's milk. Estimates were pooled using
      random-effects. Study quality was assessed by GRADE score and risk of bias by the
      Review Manager software tool. RESULTS: Four papers were included in the meta
      analysis. DM did not exert a beneficial effect of DM on the risk of preventing
      surgical NEC with respect to formula (RR: 0.45; 95% CI: 0.19-1.09). CONCLUSIONS:
      This meta-analysis indicates that DM does not exert a clear protective effect, on
      the surgical cases of NEC with respect to preterm formula. Since DM feeding
      implies remarkable extra cost for the preparation, storage and delivery of the
      milk with respect to preterm formula, stronger evidences are required to
      recommend this type of feeding as a preventive strategy for surgical NEC.
      Mother's milk, when available, could represents the best choice. PROSPERO
      REGISTRATION NUMBER: CRD42015020296.

PMID- 29566976
TI  - Implementation science theories to inform efforts for de-implementation of
      urologic oncology care practices resulting in overuse and misuse.
AB  - The field of implementation science has been conventionally applied in the
      context of increasing the application of evidence-based practices into clinical
      care, given evidence of underusage of appropriate interventions in many settings.
      Increasingly, however, there is recognition of the potential for similar
      frameworks to inform efforts to reduce the application of ineffective or
      potentially harmful practices. In this article, we provide some examples of
      clinical scenarios in which the quality problem may be overuse and misuse, and
      review relevant theories and frameworks that may inform improvement activities.

PMID- 29566977
TI  - CO suppresses prostate cancer cell growth by directly targeting LKB1/AMPK/mTOR
      pathway in vitro and in vivo.
AB  - BACKGROUND: CO is a freely diffusible gas that acts as a physiological mediator
      of many biological and cellular processes, which has been shown to possess
      anticancer effect in many kinds of cancers. However, the effect of CO on prostate
      cancer has not been demonstrated. Therefore, we analyzed the antitumor activities
      and related mechanisms of CO on prostate cancer in vitro and in vivo. METHODS:
      Cell viability of LNCaP and PC-3 cells after CORM-2 treatment was measured by CCK
      8 assay, whereas the ATP production were detected by ATP detection assay. The
      early apoptosis induced by CO was evaluated by flow cytometry, and the expression
      level of apoptosis-related molecules (Caspases 3, 8, 9 and cleaved-Caspases 3, 8,
      9) was detected using Western blot. Matrigel in vitro invasion assay was used to
      evaluate the effect of CO on cell invasion. We then evaluated the impact of CO on
      the expression of several key regulators involved in the LKB1 signaling pathway.
      At last, xenograft tumor in nude mice was used to further investigate the
      antitumor effect of CO in vivo. RESULTS: Our results showed that CO could
      significantly inhibit proliferation and invasion, and induce apoptosis in human
      prostate cancer cell lines. The expression of LKB1 could be up-regulated after CO
      treatment, and CO also could increase p-AMPK levels and decrease p-mTOR.
      Furthermore, LKB1 knockdown could weaken the effect of CO on prostate cancer
      cells. In vivo, CO treatment significantly suppressed tumor growth and induced
      apoptosis in xenografts tumor in nude mice. CONCLUSIONS: CO possesses striking
      anticancer effect in human prostate cancer cells in vitro and in vivo, which is
      largely mediated by LKB1-AMPK-mTOR axis.

PMID- 29566978
TI  - The relationship of travel distance with cystectomy access and outcomes.
AB  - PURPOSE: Regionalization of care and travel distance may result in unintended
      consequences for complex surgery such as cystectomy. Our objective was to
      evaluate effect of differential distance on cystectomy receipt among patients
      with muscle-invasive bladder cancer (MIBC) and investigate the association
      between travel distance and cystectomy outcomes such as readmission. METHODS:
      Using a linked data resource combining the NC Central Cancer Registry with claims
      data from Medicare, Medicaid, and private insurance plans, we included 736
      patients with MIBC and 1,082 who underwent cystectomy. To evaluate access,
      differential distance was calculated as the difference between the nearest
      urologist and nearest cystectomy provider. To assess outcomes, logistic
      regression was used to evaluate rehospitalization and major complications, and
      Cox proportional hazards model for survival analysis. RESULTS: To evaluate access
      and outcomes, 736 patients with MIBC and 1,082 patients undergoing cystectomy
      were evaluated, respectively. Overall, 29% (211 of 736) with MIBC underwent
      cystectomy. Differential distance was not a predictor of cystectomy receipt (odds
      ratio = 1.0; 95% CI: 1.00, 1.01). Among patients undergoing cystectomy, travel
      distance from cystectomy provider was not a significant predictor of 30- or 31 to
      90day readmissions (odds ratio = 1.0; 95% CI: 1.00, 1.00) although patients who
      lived further from their cystectomy provider were more likely to be readmitted to
      a nonindex hospital (P<0.001) when controlling for other factors. Although travel
      distance did not have a significant effect on overall survival, patients
      readmitted between 31 to 90days had worse overall survival (P<0.0001).
      CONCLUSIONS: The additional distance needed to reach a cystectomy provider did
      not predict receipt of surgery for MIBC. Furthermore, travel distance from
      cystectomy provider was not a significant predictor for subsequent readmission
      after cystectomy and did not affect overall survival.

PMID- 29566979
TI  - Beyond genes: A systematic review of environmental risk factors in specific
      reading disorder.
AB  - BACKGROUND: While an understanding of the genetic contributions to specific
      reading disorder (RD) is emerging, there is no agreement about which putative
      hazard factors are clearly involved in the aetiology of this disorder. AIMS: A
      literature review looking at the impact of environmental risk variables
      implicated in RD either per se or when interacting with the genes. METHODS AND
      PROCEDURES: We performed a systematic literature review using the following
      keywords: dyslexia OR reading disability AND environmental risk factors OR
      environmental hazard factors, in the following electronic databases: PubMed,
      Scopus and PsycINFO, without any time restrictions. OUTCOMES AND RESULTS:
      Gestational weeks and birth weight are among the pre- and peri-natal risk factors
      shown to reliably predict reading readiness and the odds of having RD.
      Inconclusive findings have been reported for maternal cigarette smoking, family
      history of psychiatric and medical diseases, and risk of miscarriage. A broad
      definition of familial socio-economic status and home literacy environment have
      been identified as good life-long risk predictors of reading skills. CONCLUSIONS
      AND IMPLICATIONS: We highlighted the need to consider environmental hazards,
      their interactions and interactions with RD-candidate genes in the study of the
      aetiology of RD in order to provide much-needed insight into how these variables
      influence reading skills.

PMID- 29566980
TI  - Heart attack and something else: Caseous degeneration of mitral anullus.

PMID- 29566981
TI  - Anxiety-related psychopathology and chronic pain comorbidity among public safety
      personnel.
AB  - Canadian Public Safety Personnel (PSP; e.g., correctional service officers,
      dispatchers, firefighters, paramedics, police officers) regularly experience
      potentially traumatic, painful, and injurious events. Such exposures increase
      risk for developing mental disorders and chronic pain, which both involve
      substantial personal and social costs. The interrelationship between mental
      disorders and chronic pain is well-established, and both can be mutually
      maintaining; accordingly, understanding the relationship between mental health
      and chronic pain among PSP is important for improving health care. Unfortunately,
      the available research on such comorbidity for PSP is sparse. The current study
      was designed to provide initial estimates of comorbidities between mental
      disorders and chronic pain across diverse PSP. Participants included 5093 PSP
      (32% women) in six categories (i.e., Call Center Operators/Dispatchers,
      Correctional Workers, Firefighters, Municipal/Provincial Police, Paramedics,
      Royal Canadian Mounted Police) who participated in a large PSP mental health
      survey. The survey included established self-report measures for mental disorders
      and chronic pain. In the total sample, 23.1% of respondents self-reported
      clinically significant comorbid concerns with both mental disorders and chronic
      pain. The results indicated PSP who reported chronic pain were significantly more
      likely to screen positive for posttraumatic stress disorder (PTSD), major
      depressive disorder, generalized anxiety disorder, social anxiety disorder, and
      alcohol use disorder. There were differences between PSP categories; but, the
      most consistent indications of comorbidity were for chronic pain, PTSD, and major
      depressive disorder. Comorbidity between chronic pain and mental disorders among
      PSP is prevalent. Health care providers should regularly assess PSP for both
      symptom domains.

PMID- 29566982
TI  - Heterogeneity in caregiver population studies.

PMID- 29566983
TI  - Use of Inner Branches for Endovascular Repair of Complex Thoracoabdominal
      Aneurysms: Necessary Evil or Bridge too Far?

PMID- 29566984
TI  - Selected mosquito borne illnesses - Dengue.

PMID- 29566985
TI  - Quality of life after pelvic ring fractures: A cross-sectional study.
AB  - BACKGROUND: Pelvic ring fractures might have consequences for health-related
      quality of life (HrQoL). The main purpose of this study was to evaluate patients'
      HrQoL after a pelvic ring fracture, considering the patients' characteristics. A
      cross-sectional study was conducted using the EuroQoL-5D (EQ-5D) and the Majeed
      pelvic score (MPS). METHODS: One hundred ninety-five patients (86%) with pelvic
      ring fractures who were conservatively or surgically treated in a level 1 trauma
      centre between 2011 and 2015 were included in this study (mean follow up: 29
      months, range 6-61). A telephone survey of all patients was conducted. Multiple
      logistic and linear regression analyses were used for statistical assessment with
      the EQ-5D and the MPS. The MPS results were split into two age groups with a cut
      off point of 65 years. RESULTS: EQ-5D: The mean EQ-5D Visual Analogue Scale (VAS)
      for Tiles A-C was, respectively, 74 (SD 18), 74 (SD 19) and 67 (SD 21), and the
      mean EQ-5D index score was, respectively, 0.81 (SD 0.23), 0.77 (SD 0.30) and 0.71
      (SD 0.26). Compared with Tile A, patients in Tile C experienced significantly
      more pain (odds ratio 6.28 (1.73-22.82 95% CI), P < 0.01). Clinically relevant
      differences in EQ-5D scores between Tile A and Tile C were seen in the domains of
      usual activities and anxiety and in the index score. MPS: The mean MPS of Tiles A
      C patients in the <65 group was, respectively, 86 (SD 15), 81 (SD 17), and 74 (SD
      16), and in the >=65 group, it was, respectively, 69 (SD 15), 68 (SD 15) and 66
      (SD 9). In the <65 group, significant differences in MPS results between the Tile
      groups regarding pain (P < 0.01) and the total MPS score (P = 0.04) were seen.
      Neither significant regression coefficients nor clinically relevant differences
      were found in the >=65 group. CONCLUSIONS: In conclusion, our study showed that
      pain was increased in patients with Tile C fractures, compared with Tiles A and
      B. Furthermore, Tile C patients had significantly lower EQ-5D index and total MPS
      scores. However, these problems were not seen in the >=65 group.

PMID- 29566986
TI  - Fractures of the femur and blood transfusions.
AB  - BACKGROUND: Blood loss estimation after trauma (i.e. physical injury) and early
      identification of potential sources of bleeding are important for planning of
      investigation and management of trauma. Long bone fractures have been reported to
      be associated with substantial volumes of blood loss requiring blood transfusion.
      The aim of this study was to assess rates and amounts of blood transfusion in the
      setting of isolated extra capsular femur fractures and to determine variables
      associated with the need for transfusion within the first 48 h of admission.
      METHODS: A retrospective cohort study was conducted of patients in The Alfred
      Trauma Registry with isolated extra capsular femur fractures over a 7-year
      period. We compared patients with a femoral shaft fracture (FSF) to patients with
      either distal femur or proximal femur fractures (i.e. extremity fracture). We
      collected data potentially associated with blood transfusion within 48 h as well
      as operation details and patient outcomes. RESULTS: There were 293 patients
      included, of which 121 had FSF and 172 extremity fracture. 105 (36%) patients
      received a blood transfusion during their admission. Admission haemoglobin (AOR
      0.92; 95%CI 0.89-0.94, p < 0.01) was the only independently associated variable
      with blood transfusion within the first 48 h of hospital admission. CONCLUSION:
      Volume of blood transfused to patients with extra-capsular femoral fractures was
      low and usually in the post-operative period. FSF, compared to femoral extremity
      fractures, were not more likely to receive blood transfusion within the first 48
      h of admission, and did not receive a higher volume of blood overall. In the
      setting of major trauma with haemorrhagic shock, alternate sources of bleeding
      should be sought.

PMID- 29566987
TI  - Efficacy and safety of novel collagen conduits filled with collagen filaments to
      treat patients with peripheral nerve injury: A multicenter, controlled, open
      label clinical trial.
AB  - INTRODUCTION: The safety and efficacy of using artificial collagen nerve conduits
      filled with collagen filaments to treat nerve defects has not been fully studied
      in humans. We conducted a multicenter, controlled, open-label study to compare
      the safety and efficacy of artificial nerve conduit grafts with those of
      autologous nerve grafts. METHODS: We included patients with a sensory nerve
      defect of <=30 mm, at the level of the wrist or a more distal location, with the
      first-line surgical methods selected according to a patient's preference. We
      compared sensory recovery using static two-point discrimination and adverse
      events between the artificial collagen nerve conduit and autologous nerve
      grafting. RESULTS: The artificial nerve conduit group included 49 patients, with
      a mean age of 42 years and nerve defect of 12.6 mm. The autologous nerve graft
      group included 7 patients, with historical data of an additional 31 patients,
      with a mean age of 36 years and nerve defect of 18.7 mm. The rate of recovery of
      sensory function at 12 months was 75% (36/49) for the artificial nerve conduit
      group and 73.7% (28/38) in the autologous nerve group. No serious adverse events
      directly associated with use of the artificial nerve conduit were identified.
      CONCLUSIONS: The treatment of nerve defects <=30 mm using artificial collagen
      nerve conduits was not inferior to treatment using autologous nerve grafts. Based
      on our data, the new artificial collagen nerve conduit can provide an alternative
      to autologous nerve for the treatment of peripheral nerve defects.

PMID- 29566988
TI  - How can MRI change the treatment strategy in apparently isolated greater
      trochanteric fracture?
AB  - INTRODUCTION: The purpose of this study was to evaluate the proportion of greater
      trochanter (GT) fractures with occult extension to the intertrochanteric region
      on magnetic resonance imaging (MRI) among apparently isolated GT fractures and to
      investigate the use of MRI for formulating a treatment strategy in patients with
      isolated GT fractures. PATIENTS AND METHODS: This retrospective cohort study
      reviewed 37 patients with isolated GT fractures on plain radiography. Surgical or
      conservative treatment was decided according to MRI findings. We divided patients
      into 3 groups according to the extension of the fracture line. In group 1, the
      fracture line was within the lateral one-third in the coronal plane. In group 2,
      the fracture line extended from the lateral one-third to the medial one-third. In
      group 3, the fracture line extended over the medial one-third and/or to the
      medial cortex of the femur. Conservative treatment was performed in groups 1 and
      2, and surgical treatment was performed in group 3. The clinical results,
      radiography findings, and MRI findings were investigated. RESULTS: MRI revealed
      hidden intertrochanteric fractures (groups 2 [n = 10] and 3 [n = 4]) in 38% of
      apparently isolated GT fractures on radiography. No displacement was found in
      groups 1 (n = 23) and 2. Of the 4 patients in group 3, 3 were treated surgically
      and achieved good functional results and 1 refused to undergo surgery and finally
      developed complete intertrochanteric fracture. This patient presented 5 days
      later with increased hip pain, and radiography demonstrated displacement of the
      fracture, prompting surgical intervention. CONCLUSIONS: The evaluation of
      apparently isolated GT fractures using MRI can be useful to diagnose the extent
      of the occult fracture and determine the treatment strategy.

PMID- 29566989
TI  - The Role of the Medical Social Worker in a Pediatric Aero-Digestive Program.
AB  - Families experience many psycho-social challenges when caring for a child with a
      tracheostomy in the home. The support of a Medical Social Worker in a Pediatric
      Aero-digestive Program is vitally important to help families navigate the
      multiple systems required to help manage the needs of medically complex child.
      The Medical Social Worker should strive to partner with families to provide
      resources and coordinate care to enhance coping and improve overall patient care
      and well-being.

PMID- 29566990
TI  - Preserving and perfusing the allograft pancreas: Past, present, and future.
AB  - The concept of organ preservation by perfusion dates back to the mid-19th
      century. Innovations since then have included temperature regulation, perfusion
      fluid composition and various pumping systems. Advances made in liver, heart and
      kidney machine preservation are now contributing to increased graft utilisation,
      assessment of graft viability and potentially improved graft survival. Pancreas
      transplantation has not benefitted to the same extent from the application of
      perfusion technology, although the need is just as great. This overview reviews
      current pancreas specific preservation techniques. We explore concepts, which
      include static cold storage, use of preservation solutions, the 'two-layer
      method', and machine perfusion. We also discuss ideas for future development.
      Narrative review of literature from inception to December 2017 using OVID
      interfaces searching EMBASE, Google Scholar, and MEDLINE databases. All studies
      relevant to pancreas perfusion and preservation were examined for clinical
      relevance with no exclusion criteria. Conference papers and presentations were
      also reviewed and included where appropriate. The application of recent advances
      in understanding in ischaemia-reperfusion as well as technical developments in
      machine preservation Ischaemia-reperfusion have the potential to improve organ
      utilisation, viability and outcome.

PMID- 29566991
TI  - On PC12 oxygen glucose deprivation and cell death.

PMID- 29566992
TI  - Attenuating effect of kaempferol on neoplastic growth in different urological
      malignancies.

PMID- 29566993
TI  - MiR-422a targets MAPKK6 and regulates cell growth and apoptosis in colorectal
      cancer cells.
AB  - The important role of miR-422a in tumor has been reported in several studies.
      Recent research discovered that the expression of miR-422a was significantly
      decreased in colorectal cancer tissues, providing miR-422a as a tumor suppressor
      in CRC. However, the concrete mechanism of miR-422a regulating CRC cell is still
      unclear. In this study, we demonstrated that miR-422a could inhibit CRC cell
      growth and promote cell apoptosis via in vitro analyses. Moreover, computational
      methods were adopted to identify the targets of miR-422a. We found MAPKK6 was the
      direct target of miR-422a. Consequently, we further elucidated that miR-422a
      inhibited CRC cell growth and induced cell apoptosis by inhibiting p38/MAPK
      pathway. Besides that, we established the tumor xenograft model using nude mice
      and the inhibitory effects on tumor volumes and weights by miR-422a mimic
      transfection were also detected. Taken together, these findings demonstrated miR
      422a exerted anti-cancer activities on CRC, which could be potentially used for
      CRC prognosis prediction and treatment.

PMID- 29566994
TI  - Volumetric Textural Analysis of Colorectal Masses at CT Colonography:
      Differentiating Benign versus Malignant Pathology and Comparison with Human
      Reader Performance.
AB  - RATIONALE AND OBJECTIVES: To (1) apply a quantitative volumetric textural
      analysis (VTA) to colorectal masses at CT colonography (CTC) for the
      differentiation of malignant and benign lesions and to (2) compare VTA with human
      performance. MATERIALS AND METHODS: A validated, quantitative VTA method was
      applied to 63 pathologically proven colorectal masses (mean size, 4.2 cm; range,
      3-8 cm) at noncontrast CTC in 59 adults (mean age, 66.5 years; range, 45.9-91.6
      years). Fifty-one percent (32/63) of the masses were invasive adenocarcinoma, and
      the remaining 49% (31/63) were large benign adenomas. Three readers with CTC
      experience independently assessed the likelihood of malignancy using a 5-point
      scale (1 = definitely benign, 2 = probably benign, 3 = indeterminate, 4 =
      probably malignant, 5 = definitely malignant). Areas under the curve (AUCs) and
      accuracy levels were compared. RESULTS: VTA achieved optimal sensitivity of 83.6%
      vs 91.7% for human readers (P = .034), with specificities of 87.5% and 77.4%,
      respectively (P = .007). No significant difference in overall accuracy was seen
      between VTA and human readers (85.5% vs 84.7%, P = .753). The AUC for
      differentiating benign and malignant lesions was 0.936 for VTA and 0.917 for
      human readers. Intraclass correlation coefficient among the human readers was
      0.76, indicating good to excellent agreement. CONCLUSION: VTA demonstrates
      excellent performance for distinguishing benign from malignant colorectal masses
      (>=3 cm) at CTC, comparable yet potentially complementary to experienced human
      performance.

PMID- 29566995
TI  - Radiotherapy induced cavernomas in adult cancer patients.
AB  - Cerebral Cavernomas (CC) are vascular malformations located in the Central
      Nervous System (CNS) characterized by endothelium-lined vascular channels without
      parenchyma between them, whose main risk is hemorrhage. The aim of this study is
      to report adult cancer patients that developed CC after radiotherapy (RT) to the
      CNS during oncological surveillance.

PMID- 29566996
TI  - The impact of chemotherapeutic treatment on the oral microbiota of patients with
      cancer: a systematic review.
AB  - OBJECTIVE: Chemotherapy is a type of systemic treatment that inhibits neoplastic
      cells (cancer cells), produces immunosuppression, and may lead to changes in the
      oral mucosa and, consequently, in the oral microbiota. The aim of this systematic
      review was to analyze, in the scientific literature, evidence of the impact of
      chemotherapy on the oral microbiota. STUDY DESIGN: The authors conducted a search
      in PubMed/MEDLINE, Scientific Electronic Library Online (SciELO), LILACS,
      ScienceDirect, Web of Science, and Cochrane Library; to identify studies that
      discussed change in the oral microbiota of patients with during chemotherapy.
      Articles published in English until July 2017 were included. The quality of a
      study was assessed by using the Ottawa-Newcastle scale. RESULTS: Of 5252 articles
      potentially relevant to this review, 17 were included in this study. Of the 17
      studies included, 16 had used culture techniques, and 1 had used genetic
      sequencing. The most frequently observed bacteria were aerobic gram-negative
      (Klebsiella spp., Escherichia coli, Enterobacter, Pseudomonas spp.), anaerobic
      gram-negative (Veillonella spp., Capnocytophaga), and gram-positive bacteria
      (Streptococcus spp., Staphylococcus spp.). CONCLUSIONS: During chemotherapy,
      patients with cancer present a more complex oral microbiota under favorable
      conditions for their development during immunosuppression, and these may be
      responsible for different serious local or systemic pathologies.

PMID- 29566997
TI  - [Quality of care and safety indicators in anticoagulated patients with non
      valvular auricular fibrillation and deep venous thromboembolic disease].
AB  - OBJECTIVES: To identify and prioritise indicators to assess the quality of care
      and safety of patients with non-valvular auricular fibrillation (NVAF) and deep
      vein thrombosis (DVT) treated with anticoagulants. MATERIALS AND METHODS: Using
      the consensus conference technique, a group of professionals and clinical
      experts, the determining factors of the NVAF and DVT care process were
      identified, in order to define the quality and safety criteria. A proposal was
      made for indicators of quality and safety that were prioritised, taking into
      account a series of pre-established attributes. The selected indicators were
      classified into indicators of context, safety, action, and outcomes of the
      intervention in the patient. RESULTS: A set of 114 health care and safety quality
      indicators were identified, of which 35 were prioritised: 15 for NVAF and 20 for
      DVT. About half (49%) of the indicators (40% for NVAF and 55% for DVT) applied to
      patient safety, and 26% (33% for NVAF and 20% for DVT) to the outcomes of
      interventions in the patient. CONCLUSIONS: The present work presents a set of
      agreed indicators by a group of expert professionals that can contribute to the
      improvement of the quality of care of patients with NVAF and DVT treated with
      anticoagulants.

PMID- 29566998
TI  - Renal Neoplasm During Pregnancy: A Single Center Experience.

PMID- 29566999
TI  - Bilateral Testicular Germ Cell Tumors: A Case-Series From a UK-Based Tertiary
      Referral Center Over 19 Years.

PMID- 29567000
TI  - No Difference in Outcomes 12 and 24 Months After Lower Extremity Total Joint
      Arthroplasty: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: A better understanding of how patient-reported outcome measures
      (PROMs) change after total knee and hip arthroplasties (TKA and THA) is needed to
      support the minimum arbitrary follow-up of 24-months required by orthopedic
      journals. Therefore, our purpose was to perform a systematic review and meta
      analysis of the THA and TKA literature to determine if equivalence exists between
      12- and 24-month outcomes data. METHODS: A search was performed using the PubMed
      and EMBASE databases for primary and revision THA and TKA studies reporting PROMs
      data at both 12 and 24 months. Reports on PROMs for TKA and THAs were included
      for meta-analysis to detect statistical differences at 12 and 24 months. RESULTS:
      A total of 15 reports from 9 TKA (n = 1564) and 6 THA (n = 740) reports were
      analyzed. The mean change between 12 and 24 months for Knee Society Score was
      0.15 absolute points (95% confidence interval [CI]: 0.97-1.06, P = .13) and for
      Western Ontario and McMaster Universities Osteoarthritis index was 0.50 absolute
      points (95% CI: 0.94-1.07, P = .49). The mean change between 12 and 24 months for
      Harris Hip Score was 2.01 absolute points (95% CI: 0.94-1.1, P = .22) and for
      short form was 0.02 absolute points (95% CI: 0.92-1.08, P = .94). CONCLUSION: No
      different outcomes were found within THA and TKA for 4 PROMs at 12- and 24-month
      follow-up. Although the findings from this study do not alleviate the need for
      collecting data from longer follow-up periods, there may not be additional value
      in collecting short-term outcomes data in routine practice at both 1 and 2 years.

PMID- 29567001
TI  - The James A. Rand Young Investigator's Award: Battling the Opioid Epidemic with
      Prospective Pain Threshold Measurement.
AB  - BACKGROUND: Responsible analgesic prescribing is paramount in the opioid epidemic
      era, yet no standardized protocol exists. We aim to (1) quantify and correlate
      outpatient opioid need after total knee and hip arthroplasties (TKA and THA) with
      preoperative objective pain pressure thresholds (PPTs) and subjective pain
      measures and (2) report incidence of nonsurgical opioid prescriptions 6 weeks
      postoperatively. METHODS: Prospectively, PPTs were measured using an algometer
      with a maximum force of 20 pounds in 160 consecutive patients (90 TKA and 70
      THA). Two locations were tested: operative joint (medial epicondyle TKA and
      lateral iliac crest THA) and ipsilateral olecranon for systemic control. Visual
      Analog Score, Pain Severity Score, Pain Interference Score, and subjective pain
      threshold were obtained. Six-week outpatient narcotic consumption morphine
      equivalents recorded and prescriptions crosschecked with the state Controlled
      Substance Reporting System. Multivariate analysis was performed to evaluate local
      and/or systemic PPT and subjective measures with narcotic consumption. RESULTS:
      Average operative site and systemic PPT was 6.91 and 7.72 pounds force,
      respectively. Subjective averages: Visual Analog Score 7.14, Pain Severity Score
      5.05, Pain Interference Score 5.16, and perceived threshold 6.77. Six-week
      average outpatient narcotic consumption was 314.9 morphine equivalents or 125
      five milligram oxycodones. Twenty percent received opioids from outside
      providers. Linear regression revealed a negative correlation between operative
      site PPT (-0.26; P = .047) and systemic PPT (-0.31; P = .021). Subjective pain
      metrics failed to meet significance. CONCLUSION: This novel study demonstrated a
      statistically significant negative correlation between preoperative pain
      threshold and outpatient narcotic consumption. Twenty percent of patients
      received opioid prescriptions outside orthopedic providers in the 6 weeks after
      surgery highlighting the importance of interdisciplinary communication.

PMID- 29567002
TI  - How Much Pain Is Significant? Defining the Minimal Clinically Important
      Difference for the Visual Analog Scale for Pain After Total Joint Arthroplasty.
AB  - BACKGROUND: The ability to detect changes in patient-perceived pain after total
      joint arthroplasty (TJA) is critical to manage postoperative pain. The minimal
      clinically important difference (MCID) for visual analog scale for pain (VAS-P)
      has not been investigated in this population. This study investigated the MCID
      for VAS-P in the TJA population. METHODS: Postoperative pain scores were
      collected on 139 total hip arthroplasty (THA) and 165 total knee arthroplasty
      (TKA) patients. VAS-P was measured and Likert scores for changes in pain recorded
      together throughout the hospitalization per patient. Using a linear mixed model,
      the mean difference between preceding and current VAS-P was calculated and
      correlated with Likert score, when the patient reported at least slight
      improvement or worsening in pain, defining the MCID. Minimal detectable change
      was calculated using the VAS-P standard error of the means for patients reporting
      "no change." RESULTS: For THA, the overall mean and average highest VAS-P were
      35.0 mm and 50.4 mm, respectively. For TKA, the overall mean and average highest
      VAS-P were 42.6 mm and 61.1 mm, respectively. The minimal detectable change in
      VAS-P was 14.9 mm for THA and 16.1 mm for TKA. The MCID for THA and TKA pain
      improvement was -18.6 mm and -22.6 mm, respectively, and for worsening was 23.6
      mm and 29.1 mm, respectively. CONCLUSION: In the postoperative TJA population,
      VAS-P MCID changes depend on the type of surgical intervention, and whether pain
      is improving or worsening. Statistically significant VAS-P, improving -18.6 mm
      and -22.6 mm for THA and TKA patients, respectively, sets a reasonable threshold
      to identify clinically meaningful pain intervention with high specificity.

PMID- 29567003
TI  - A Computer Model of Mid-Flexion Instability in a Balanced Total Knee
      Arthroplasty.
AB  - BACKGROUND: Some patients have mid-flexion instability despite stability at 0
      degrees  and 90 degrees  of flexion. This study aims to determine the effects of
      total knee arthroplasty (TKA) stability while changing femur implant size and
      position. METHODS: A computational analysis was performed simulating knee flexion
      of posterior stabilized (PS) and cruciate retaining (CR) TKA designs. Deviations
      from the ideal TKA implant position were simulated by adjusting tibiofemoral
      proximal-distal position and femur anterior-posterior position as well as implant
      size. Forces in ligaments connecting the femur and tibia were collected. Total
      tibiofemoral ligament load for mid-knee flexion of 15 degrees -75 degrees  was
      analyzed vs proximal-distal implant position, implant size, implant design, and
      knee flexion for PS and CR knees. Posterior cruciate ligament load was also
      analyzed for CR knees. RESULTS: Total tibiofemoral ligament load was
      significantly reduced by a more proximal tibiofemoral and anterior femur position
      (P < .001). Implant size did not have a significant effect on tibiofemoral
      ligament load (P > .1). Implant design and knee flexion significantly influenced
      total tibiofemoral ligament load (P < .001), but the interactions with implant
      proximal-distal position were not significant (P > .2), indicating that implant
      proximal-distal position had a similar effect across the 15 degrees -75 degrees 
      knee flexion range for both studied PS and CR implant designs. CONCLUSION: PS and
      CR TKA can be well-balanced at 0 degrees  and 90 degrees  knee flexion and have
      instability in mid-flexion. Elevating the joint line and shifting the femur
      anteriorly can cause the knee to be too loose in mid-flexion.

PMID- 29567004
TI  - Suicide in parachuting: A case report and review of the literature.
AB  - Skydiving fatalities are mostly accidental and the result of human errors.
      However, suicides may be greatly underreported in skydivers. We present the case
      of a young civilian skydiver who committed suicide by jumping from an altitude of
      4000m without activating his chutes. Witnesses reported that the victim had
      remained in a freefall position until ground impact. Besides an extensive blunt
      trauma, the autopsy showed an antero-posterior flattening of the body with
      symmetrical abrasions on its front, which were consistent with a high-energy
      impact on the ground in a "belly-down" position. Police investigation revealed
      that the victim had expressed suicidal thoughts in text messages before jumping
      from the airplane, and examination of his equipment showed that he had disabled
      the security system allowing the reserve chute to be automatically deployed at
      low altitude. To the best of our knowledge, this is the first case of suicide of
      a skydiver that has been described in the scientific literature. A suicidal
      intent should be assumed in skydiving fatalities involving jumpers with operable
      but un-activated parachutes on their back. This case highlights the importance of
      a thorough forensic investigation in such circumstances to ascertain the manner
      of death.

PMID- 29567005
TI  - Is autofluorescence inferior to chromoendoscopy for dysplasia detection in
      ulcerative colitis?

PMID- 29567007
TI  - Reported Influences on Restaurant-Type Food Selection Decision Making in a
      Grocery Store Chain.
AB  - OBJECTIVE: To examine food decision-making priorities for restaurant-type foods
      at grocery stores and determine whether adding calorie information, as required
      by federal menu labeling laws, affected decision-making priorities. DESIGN:
      Natural experiment: intervention and control groups with baseline and follow-up.
      SETTING: Regional grocery store chain with 9 locations. PARTICIPANTS:
      Participants (n = 393; mean age, 54.8 +/- 15.1 years) were primarily women (71%)
      and Caucasian (95%). INTERVENTION: Data were collected before and after calorie
      information was added to restaurant-type foods at 4 intervention locations. MAIN
      OUTCOME MEASURE(S): Primary influencers of food selection decision making for
      restaurant-type foods and frequency of use of nutrition information. ANALYSIS:
      Quantitative analysis examined the top 3 influencers of food selections and chi
      square goodness of fit test determined whether the calorie labeling intervention
      changed food decision-making priorities. Qualitative data were used to describe
      responses. RESULTS: Taste, cost, and convenience were the most frequently
      reported influencers of restaurant-type food selections; 20% of participants
      rated calories as influential. Calorie labeling did not affect food selection
      decision making; 16% of participants in intervention stores noticed calorie
      labels. Qualitative explanations confirmed these findings. CONCLUSIONS AND
      IMPLICATIONS: Menu labeling laws increase access to calorie information; however,
      use of this information is limited. Additional interventions are needed to
      encourage healthier restaurant-type food selections in grocery stores.

PMID- 29567006
TI  - Chromoendoscopy versus autofluorescence imaging for neoplasia detection in
      patients with longstanding ulcerative colitis (FIND-UC): an international,
      multicentre, randomised controlled trial.
AB  - BACKGROUND: Patients with longstanding ulcerative colitis undergo regular
      dysplasia surveillance because they have an increased colorectal cancer risk.
      Autofluorescence imaging and chromoendoscopy improve dysplasia detection. The aim
      of this study was to determine whether autofluorescence imaging should be further
      studied as an alternative method for dysplasia surveillance in patients with
      longstanding ulcerative colitis. METHODS: This prospective, international,
      randomised controlled trial included patients from an ulcerative colitis
      dysplasia surveillance cohort from five centres in the Netherlands and the UK.
      Eligible patients were aged 18 years or older who were undergoing dysplasia
      surveillance after being diagnosed with extensive colitis (Montreal E3) at least
      8 years before study start or with left-sided colitis (Montreal E2) at least 15
      years before study start. Randomisation (1:1) was minimised for a previous
      personal history of histologically proven dysplasia and concomitant primary
      sclerosing cholangitis. The coprimary outcomes were the proportion of patients in
      whom at least one dysplastic lesion was detected and the mean number of
      dysplastic lesions per patient. The relative dysplasia detection rate, calculated
      as the ratio of the detection rates by autofluorescence imaging and
      chromoendoscopy, needed to be more than 0.67 (using an 80% CI) for both primary
      outcomes to support a subsequent large non-inferiority trial. Outcomes were
      analysed on a per-protocol basis. The trial is registered at the Netherlands
      Trial Register, number NTR4062. FINDINGS: Between Aug 1, 2013, and March 10,
      2017, 210 patients undergoing colonoscopy surveillance for longstanding
      ulcerative colitis were randomised for inspection with either autofluorescence
      imaging (n=105) or chromoendoscopy (n=105). Dysplasia was detected in 13 (12%)
      patients by autofluorescence imaging and in 20 patients (19%) by chromoendoscopy.
      The relative dysplasia detection rate of autofluorescence imaging versus
      chromoendoscopy for the proportion of patients with ulcerative colitis with at
      least one dysplastic lesion was 0.65 (80% CI 0.43-0.99). The mean number of
      detected dysplastic lesions per patient was 0.13 (SD 0.37) for autofluorescence
      imaging and 0.37 (1.02) for chromoendoscopy (relative dysplasia detection rate
      0.36, 80% CI 0.21-0.61). Adverse events were reported for two patients in the
      autofluorescence imaging group (one patient had intraprocedural mild bleeding,
      and one patient had abdominal pain) and for three patients in the chromoendoscopy
      group (two patients had intraprocedural mild bleeding, and one patient had
      perforation). INTERPRETATION: Autofluorescence imaging did not meet criteria for
      proceeding to a large non-inferiority trial. Therefore, existing autofluorescence
      imaging technology should not be further investigated as an alternative dysplasia
      surveillance method. FUNDING: Olympus Europe and Olympus Keymed.

PMID- 29567008
TI  - An Obesity Risk Assessment Tool for Young Children: Validity With BMI and
      Nutrient Values.
AB  - OBJECTIVE: Demonstrate validity and reliability for an obesity risk assessment
      tool for young children targeting families' modifiable home environments. DESIGN:
      Longitudinal design with data collected over 100 weeks. SETTING: Head Start and
      the Special Supplemental Nutrition Program for Women, Infants, and Children.
      PARTICIPANTS: Parent-child pairs (n = 133) provided food behavior assessments; 3
      child-modified, 24-hour dietary recalls; 3 >= 36-hour activity logs; and measured
      heights and weights. MAIN OUTCOME MEASURE: Five measures of validity and 5 of
      reliability. RESULTS: Validity was excellent for the assessment tool, named
      Healthy Kids, demonstrating an inverse relationship with child body mass index
      percentile-for-age (P = .02). Scales were significantly related to hypothesized
      variables (P <= .05): fruit or vegetable cup equivalents; folate; vitamins A, C,
      and D; beta-carotene; calcium; fiber; sugar; screen, sleep, and physical activity
      minutes; and parent behaviors. Measures of reliability were acceptable.
      CONCLUSIONS AND IMPLICATIONS: Overall, children with higher Healthy Kids scores
      had a more healthful profile as well as lower body mass index percentiles-for-age
      1.5 years later. Healthy Kids has potential for use by nutrition professionals as
      a screening tool to identify young children most at risk for excess weight gain,
      as an evaluation to assess intervention impact, and as a counseling tool to
      tailor intervention efforts. Future research should include validation in other
      settings and with other populations.

PMID- 29567009
TI  - Trend in unequal geographical distribution of doctors by age and sex in Japan
      from 2004 to 2014.
AB  - OBJECTIVES: In Japan, the proportion of female doctors and elderly doctors is
      increasing as in other countries. We investigated the relationship between
      doctors' demographic changes and their geographical distribution. STUDY DESIGN: A
      national database study. METHODS: We assessed trends in unequal geographical
      distribution of the number of doctors by sex and age from 2004 to 2014 in Japan.
      RESULTS: The Gini coefficient values for the number of female doctors (0.18) were
      larger than those for male doctors across all generations (0.13-0.14). The Gini
      coefficient values for the number of elderly doctors aged 60 years and older
      (male: 0.12, female: 0.18-0.23) were larger than those for majority age groups
      aged 40-59 years (male: 0.10, female: 0.16-0.17). CONCLUSION: The persisting
      geographical maldistribution of doctors may be associated with demographic
      changes, such as increase in the number of female doctors.

PMID- 29567010
TI  - Effect of increasing temperature on daily hospital admissions for schizophrenia
      in Hefei, China: a time-series analysis.
AB  - OBJECTIVE: To investigate the relationship between ambient temperature and
      hospital admissions for schizophrenia in Hefei, China. STUDY DESIGN: An
      ecological design was used to explore the effect of ambient temperature on
      hospital admissions for schizophrenia. METHODS: Daily data on hospital admissions
      for schizophrenia and meteorological data for the warm season (May-October) in
      2005-2014 were obtained from Anhui Mental Health Centre and Hefei Bureau of
      Meteorology, respectively. Poisson generalised linear regression model combined
      with a distributed lag non-linear model was used to analyse the effects of
      temperature on admissions for schizophrenia. Stratified analyses according to
      individual characteristics, such as age and sex, were also conducted. RESULTS: A
      significant relationship was found between ambient temperature and admissions for
      schizophrenia. High temperature appeared to have a delayed effect on admissions
      for schizophrenia, and a temperature of 28 degrees C (75th percentile) at lag 0-4
      days was associated with a 7% (95% confidence interval: 4-11%) increase in
      admissions for schizophrenia. Stratified analyses showed that male patients,
      patients aged 21-60 years and married patients were more vulnerable to high
      temperature, and the temperature effects for those groups occurred at a lag of 1
      day. CONCLUSION: High temperature poses significant risks for schizophrenia in
      subtropical regions. Future preventive measures for reducing the occurrence of
      schizophrenia should be considered for susceptible populations.

PMID- 29567011
TI  - Impact of ambient fine particulate matter air pollution on health behaviors: a
      longitudinal study of university students in Beijing, China.
AB  - OBJECTIVES: Poor air quality has become a national public health concern in
      China. This study examines the impact of ambient fine particulate matter (PM2.5)
      air pollution on health behaviors among college students in Beijing, China. STUDY
      DESIGN: Prospective cohort study. METHODS: Health surveys were repeatedly
      administered among 12,000 newly admitted students at Tsinghua University during
      2012-2015 over their freshman year. Linear individual fixed-effect regressions
      were performed to estimate the impacts of ambient PM2.5 concentration on health
      behaviors among survey participants, adjusting for various time-variant
      individual characteristics and environmental measures. RESULTS: Ambient PM2.5
      concentration was found to be negatively associated with time spent on walking,
      vigorous physical activity and sedentary behavior in the last week, but
      positively associated with time spent on nighttime/daytime sleep among survey
      participants. An increase in the ambient PM2.5 concentration by one standard
      deviation (36.5 MUg/m3) was associated with a reduction in weekly total minutes
      of walking by 7.3 (95% confidence interval [CI] = 5.3-9.4), a reduction in weekly
      total minutes of vigorous physical activity by 10.1 (95% CI = 8.5-11.7), a
      reduction in daily average hours of sedentary behavior by 0.06 (95% CI = 0.02
      0.10) but an increase in daily average hours of nighttime/daytime sleep by 1.07
      (95% CI = 1.04-1.11). CONCLUSIONS: Ambient PM2.5 air pollution was inversely
      associated with physical activity level but positively associated with sleep
      duration among college students. Future studies are warranted to replicate study
      findings in other Chinese cities and universities, and policy interventions are
      urgently called to reduce air pollution level in China's urban areas.

PMID- 29567012
TI  - Staged laparoscopic traction orchiopexy for intra-abdominal testis: Is it always
      feasible?
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic orchiopexy for intra-abdominal testis is
      a well-known and commonly practiced technique. The traction technique is based on
      elongation of the testicular vessels without cutting them, in contrast with the
      two-stage Fowler-Stephens technique in which the testicular vessels are divided.
      The current study evaluated the feasibility of the traction technique according
      to the type of intra-abdominal testis. PATIENTS AND METHODS: The study included
      20 boys with 22 intra-abdominal testes and who underwent staged laparoscopic
      traction orchiopexy between October 2013 and October 2015. Eighteen testes were
      proximal to the internal ring by <2 cm (type III), while the remaining four were
      high and away from the internal ring by >2 cm (type IVa). The patients' ages
      ranged between 6 months and 5 years (mean 2.2 years; median 2 years). Patients
      were followed up for 1 year for testicular atrophy and satisfactory scrotal site
      relocation. RESULTS: This study did not detect any cases of testicular atrophy
      among the participants (0/22), while failure to achieve satisfactory scrotal site
      was found in two out of the four cases with type IVa intra-abdominal testes.
      DISCUSSION: Traction techniques for elongating the testicular vessels were
      employed years ago, but this was revisited by Shehata in 2008. It has the
      advantage of preserving the main testicular blood supply, which can be reflected
      by the decreasing rate of testicular atrophy when compared with the Fowler
      Stephens orchiopexy. The results of the traction technique may be less
      satisfactory regarding the testicular location for higher types of intra
      abdominal testes (type IVa). CONCLUSION: Staged laparoscopic traction orchiopexy
      was a feasible technique for intra-abdominal testes (within 2 cm of the internal
      ring), but the results were less satisfactory when applied for higher intra
      abdominal testes (type IVa).

PMID- 29567013
TI  - Response to the comment on "Hypospadias repair with the glanular-frenular collar
      (GFC) technique".

PMID- 29567014
TI  - Simulation in paediatric urology and surgery. Part 1: An overview of educational
      theory.
AB  - Surgical training has changed radically in the last few decades. The traditional
      Halstedian model of time-bound apprenticeship has been replaced with competency
      based training. Advanced understanding of mastery learning principles has vastly
      altered educational methodology in surgical training, in terms of instructional
      design, delivery of educational content, assessment of learning, and programmatic
      evaluation. As part of this educational revolution, fundamentals of simulation
      based education have been adopted into all levels and aspects of surgical
      training, requiring an understanding of concepts of fidelity and realism and the
      impact they have on learning. There are many educational principles and theories
      that can help clinical teachers understand the way that their trainees learn. In
      the acquisition of surgical expertise, concepts of mastery learning, deliberate
      practice, and experiential learning are particularly important. Furthermore,
      surgical teachers need to understand the principles of effective feedback, which
      is essential to all forms of skills learning. This article, the first of two
      papers, presents an overview of relevant learning theory for the busy paediatric
      surgeon and urologist. Seeking to introduce the concepts underpinning current
      changes in surgical education and training, providing practical tips to optimise
      teaching endeavours.

PMID- 29567015
TI  - Re: Kieran et al.: See, Do, Teach? A Review of Contemporary Literature and Call
      to Action for Communication Skills Teaching in Urology (Urology 2018;114:33-40).

PMID- 29567016
TI  - Primary Synovial Sarcoma of the Kidney: A Rare Presentation.
AB  - Primary renal synovial sarcoma (PRSS) is a rare entity. It should be considered
      as one of the differential diagnoses of spindle cell tumors of the kidney.
      Immunohistochemistry and genetic translocation studies should be used to confirm
      the diagnosis. Because of a lack of consistent literature data regarding the
      treatment options, management of PRSS remains a therapeutic challenge. In view of
      the chemosensitive nature of the tumor, we propose a multimodality treatment in
      form of surgery and chemotherapy in patients with PRSS. Here we report a rare
      case of PRSS in a 17-year-old adolescent.

PMID- 29567017
TI  - Reply by the Authors.

PMID- 29567018
TI  - Mechanism of Action of the Transobturator Sling for Post-Radical Prostatectomy
      Incontinence: A Multi-institutional Prospective Study Using Dynamic Magnetic
      Resonance Imaging.
AB  - OBJECTIVE: To compare the length of the membranous (functional) urethra in male
      patients who underwent the male transobturator sling (TOS) for postradical
      prostatectomy urinary incontinence (PPI). The TOS is in established use for
      treatment of PPI; however, the precise mechanism of action is unknown. MATERIALS
      AND METHODS: This is a prospective case-controlled study on men undergoing male
      TOS surgery from 2008 to 2014. The comparison arm included patients without
      incontinence after radical prostatectomy. All participants underwent dynamic
      magnetic resonance imaging (MRI) at baseline and this was repeated after TOS
      placement for those who underwent the procedure. Three standardized points were
      measured using MRI and compared in both groups in addition to clinical measures.
      RESULTS: Thirty-nine patients were enrolled and 31 patients completed the
      protocols. The controls (N = 14) had a longer vesicourethral anastomosis to
      urethra measured at the penile bulb (functional urethral length) distance
      compared to the pre-TOS group at rest (1.92 cm controls vs 1.27 cm pre-TOS, P =
      .0018) and at Valsalva (2.13 cm controls vs 1.72 cm pre-TOS, P = .0371).
      Placement of the sling (N = 17) increased the functional urethral length distance
      at rest (1.92 cm control vs 1.53 cm post-TOS, P = .09) and at Valsalva (1.94 cm
      post-TOS vs 2.13 cm control, P = .61), so that the difference was no longer
      statistically significant. CONCLUSION: We identified that one possible mechanism
      in improvement in stress urinary incontinence post-TOS placement is the
      lengthening of the vesicourethral anastomosis to bulbar-urethra distance. This is
      the first such study utilizing dynamics MRI in post prostatectomy controls,
      incontinent pre-TOS, and post-TOS to assess and show these findings.

PMID- 29567020
TI  - [Encephalitis as a complication of Herpes Zoster ophtalmicus].

PMID- 29567019
TI  - [Systemic safety following intravitreal injections of anti-VEGF].
AB  - The goal of this manuscript is to assess data suggesting that intravitreal
      injection of anti-vascular endothelial growth factors (anti-VEGFs) could result
      in systemic adverse events (AEs). The class-specific systemic AEs should be
      similar to those encountered in cancer trials. The most frequent AE observed in
      oncology, hypertension and proteinuria, should thus be the most common expected
      in ophthalmology, but their severity should be lower because of the much lower
      doses of anti-VEGFs administered intravitreally. Such AEs have not been
      frequently reported in ophthalmology trials. In addition, pharmacokinetic and
      pharmacodynamic data describing systemic diffusion of anti-VEGFs should be
      interpreted with caution because of significant inconsistencies reported. Thus,
      safety data reported in ophthalmology trials and pharmacokinetic/pharmacodynamic
      data provide robust evidence that systemic events after intravitreal injection
      are very unlikely. Additional studies are needed to explore this issue further,
      as much remains to be understood about local and systemic side effects of anti
      VEGFs.

PMID- 29567022
TI  - Pseudo-panuveitis masquerade syndrome associated with an orbital and systemic
      MALT-type B-cell lymphoma.

PMID- 29567021
TI  - [Atopic keratoconjunctivitis: One allergy may mask another. A clinical
      observation with two types of hypersensitivity reactions: IgE-mediated and non
      IgE-mediated].
AB  - Allergies are frequently implicated in ophthalmologic practice. These typically
      benign allergies can be potentially severe for the ocular surface and have an
      impact in everyday life. We relate, through a case of keratoconjunctivitis
      involving 2 types of hypersensitivity, the various triggers and therapeutic
      choices to allow a more effective treatment.

PMID- 29567023
TI  - Strategies for enhancing microbial tolerance to inhibitors for biofuel
      production: A review.
AB  - Using lignocellulosic biomass for the production of renewable biofuel provides a
      sustainable and promising solution to the crisis of energy and environment.
      However, the processes of biomass pretreatment and biofuel fermentation bring a
      variety of inhibitors to microbial strains. These inhibitors repress microbial
      growth, decrease biofuel yields and increase fermentation costs. The production
      of biofuels from renewable lignocellulosic biomass relies on the development of
      tolerant and robust microbial strains. In recent years, the advancement of
      tolerance engineering and evolutionary engineering provides powerful platform for
      obtaining host strains with desired tolerance for further metabolic engineering
      of biofuel pathways. In this review, we summarized the inhibitors derived from
      biomass pretreatment and biofuel fermentation, the mechanisms of inhibitor
      toxicity, and the strategies for enhancing microbial tolerance.

PMID- 29567024
TI  - Jejunal arterial access for retrograde mesenteric stenting.
AB  - Endovascular approaches have replaced open surgical revascularization in most
      patients with mesenteric ischemia; however, flush ostial occlusions may not be
      amenable to traditional antegrade access. Retrograde mesenteric stenting has been
      previously described, but this technique requires a formal laparotomy and
      dissection of the proximal superior mesenteric artery. We present here a
      modification of this technique that requires only a "mini-laparotomy" and no open
      vascular repair of the superior mesenteric artery as well as a review of our
      initial institutional experience with this procedure. Our approach differs from
      previously described work by minimizing mesenteric dissection, avoiding the need
      for repair of an arteriotomy, and limiting the size of the laparotomy incision in
      this population of profoundly comorbid patients.

PMID- 29567025
TI  - Endovascular thoracic aortic repair in confirmed or suspected genetically
      triggered thoracic aortic dissection.
AB  - OBJECTIVE: Endovascular repair in patients with connective tissues disorders is
      not recommended because of concern for repair failure. The aim of this study was
      to investigate thoracic endovascular aortic repair (TEVAR) outcomes in patients
      with confirmed or suspected syndromic and nonsyndromic genetically triggered
      thoracic aortic dissection. METHODS: We analyzed data for patients with
      descending thoracic aorta (DTA) dissection treated with TEVAR from the National
      Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular
      Conditions (GenTAC). Enrolled patients had confirmed (syndromic or familial) or
      suspected genetically triggered thoracic aortic disease. The latter group
      includes patients with sporadic aortic dissection presenting at 50 years of age
      or younger in the absence of a family history or syndromic features. RESULTS:
      Between 2006 and 2014, there were 371 patients with DTA dissection enrolled in
      GenTAC. TEVAR was performed in 31 cases (58.1% male; median age, 47 years; range,
      21.3-65.6 years). Genetically triggered aortic dissection was confirmed in 18
      cases, and an additional 13 cases had suspected genetically triggered dissection
      because of early onset of presentation. TEVAR was performed in nine patients with
      type A aortic dissection: five in conjunction with acute type A dissection repair
      and four in the chronic phase to treat aneurysmal degeneration of the residual
      dissected DTA (median interval to TEVAR, 2.1 years). TEVAR was also performed in
      22 cases of type B aortic dissection (TBAD), 12 acute and 10 chronic (median
      interval to TEVAR, 1.6 years). There were no perioperative deaths. Median follow
      up for all cases was 2 years (range, 0.4 month-7 years). Reinterventions after
      TEVAR were performed in 13 cases (41.9%). This included urgent repair of three
      retrograde ascending aorta dissections occurring after TEVAR for acute TBAD (25%)
      and seven thoracoabdominal repairs with stent graft explantation (22.6%) at a
      median of 7 months after TEVAR (range, 1-16.6 months). CONCLUSIONS: TEVAR in
      patients with genetically triggered aortic dissections can be lifesaving in the
      acute setting though associated with high risk of retrograde aortic dissection in
      acute TBAD. For chronic dissection-related DTA aneurysmal degeneration, TEVAR
      could potentially be lifesaving in patients deemed too high risk for open
      surgical repair. Close postoperative surveillance is required, given the risk of
      subsequent device failure and need for reintervention. Because these
      circumstances are rare, multicenter prospective enrollment of patients with
      genetically triggered aortic disease is essential to delineate the indications
      for and risks of TEVAR in this heterogeneous population.

PMID- 29567026
TI  - Serum tumor necrosis factor alpha levels are associated with new ischemic brain
      lesions after carotid artery stenting.
AB  - OBJECTIVE: New diffusion-weighted imaging (DWI) lesions on magnetic resonance
      imaging (MRI) after carotid artery stenting (CAS) are associated with an
      increased risk of future cerebrovascular events. Therefore, we evaluated the
      association between the expression levels of serum inflammatory markers and new
      DWI lesions after CAS and the presence of intraplaque hemorrhage (IPH). We also
      explored the mechanisms underlying this association. METHODS: A total of 225
      inpatients with severe carotid artery stenosis were consecutively enrolled in
      this cohort study. Serum inflammatory marker levels were detected in all patients
      by enzyme-linked immunosorbent assay. In the final analysis, 128 patients who
      underwent CAS and received pretreatment and post-treatment MRI scans were
      enrolled. DWI was performed to detect new ischemia brain lesions. T1-weighted, T2
      weighted, and time-of-flight sequences were also conducted to identify IPH.
      RESULTS: Serum tumor necrosis factor alpha (TNF-alpha) levels were significantly
      higher in symptomatic patients as well as in IPH+ patients identified by carotid
      MRI. New DWI lesions were identified in 50% of patients after CAS. Univariate
      analysis showed that DWI+ patients after CAS exhibited older mean age, higher
      mean TNF-alpha levels, and more IPH on preoperative MRI and were less likely to
      have right carotid stenosis than DWI- patients. Multivariate logistic regression
      analyses revealed that serum TNF-alpha concentrations were associated with new
      DWI lesions after CAS (odds ratio, 1.245; 95% confidence interval, 1.068-1.451; P
      = .005). Finally, the specificity and sensitivity of serum TNF-alpha levels in
      predicting DWI+ patients after CAS were 0.828 and 0.453, respectively.
      CONCLUSIONS: Higher serum TNF-alpha levels are associated with a higher
      likelihood of new DWI lesions after CAS and the presence of IPH. Therefore, TNF
      alpha is a potentially valuable predictor of acute ischemic cerebral lesions
      after CAS and the presence of IPH.

PMID- 29567027
TI  - A prospective randomized study of bovine carotid artery biologic graft and
      expanded polytetrafluoroethylene for permanent hemodialysis access.
AB  - OBJECTIVE: Arteriovenous grafts (AVGs) remain reliable substitutes for permanent
      hemodialysis access in scenarios that preclude the placement of native
      arteriovenous fistulas (AVFs). The majority of AVGs are constructed of expanded
      polytetrafluoroethylene (ePTFE), which is relatively inexpensive and readily
      available, but synthetic AVGs have poor patency rates. On the other hand,
      biologic grafts confer an advantage by virtue of their inherent similarity to the
      native human vasculature. However, evidence to support the current preference of
      synthetic conduits over biologic grafts in clinical practice is scarce. The aim
      of this protocol is to propose a contemporary re-evaluation and comparison
      between ePTFE and bovine carotid artery (BCA) grafts. METHODS: This prospective
      randomized controlled trial is being conducted at an academic hospital center. A
      total of 100 patients at least 18 years of age and undergoing AVG placement will
      be recruited and prospectively randomized into two parallel groups with a 1:1
      allocation ratio. Patients eligible to receive AVF and those with a known
      allergic reaction or history of intolerance to any ePTFE or BCA component will
      not be included in the study. Moreover, patients with a recent active infection
      at the site of previous AVG placement and patients with a bleeding disorder, an
      active malignant disease, or a life expectancy <1 year or who refuse blood
      transfusion and pregnant women will be excluded. Patients will receive either BCA
      (experimental) or standard ePTFE grafts (control) in compliance with the National
      Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines for AVG
      creation. Primary end points include primary, primary assisted, secondary, and
      functional patency at 1 year and 2 years after graft placement. Secondary
      outcomes include complications (pseudoaneurysms, infections, and steal syndrome)
      and reintervention rates during the first and second postoperative years.
      Outcomes will be assessed and documented every 6 months. RESULTS: Once the study
      is completed, analysis of the data will be performed using univariate methods,
      and Kaplan-Meier and multivariate Cox proportional regression analyses will be
      employed to evaluate and to compare outcomes between BCA and ePTFE over time.
      CONCLUSIONS: The creation of a functional and durable dialysis vascular access is
      crucial in the treatment of patients with end-stage renal disease and is a
      challenging quest for vascular surgeons. The proposed study compares the outcomes
      of synthetic and biologic AVG options in patients who are poor candidates for a
      native AVF. This will help derive contemporary evidence and improve the care of
      vascular access patients.

PMID- 29567028
TI  - Analysis of host Toll-like receptor 3 and RIG-I-like receptor gene expression in
      patients with abdominal aortic aneurysm.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular disease relatively
      common in the elderly population. Although some events that contribute to the
      development and progression of AAA are known, there are limited data examining
      the association of Toll-like receptor 3 (TLR3) and RIG-I-like receptor expression
      with the pathogenesis of AAAs. In this study, we investigated the gene and
      protein expression of TLR3 and RIG-I-like receptors (RIG-I and MDA5) in aortic
      wall and blood of AAA patients and examined the relationship between their
      expression and immune response. METHODS: Total RNA was extracted from aortic wall
      tissues and blood samples collected from 20 patients with AAA and blood samples
      of 17 healthy volunteers without aortic aneurysm. To evaluate the DDX58 (RIG-I),
      IFIH1 (MDA5), and TLR3 gene expression level, quantitative real-time polymerase
      chain reaction was used. Extracellular cytokine and pattern recognition receptor
      levels were quantified by enzyme-linked immunosorbent assays. RESULTS: TLR3, RIG
      I, and MDA5 were constitutively expressed in both aortic tissues and blood
      samples from AAA patients and healthy volunteers. In patients with AAA, higher
      TLR3 expression in aortic tissues than in blood was found (P = .004). The DDX58
      messenger RNA expression was higher in blood of patients with AAA compared with
      healthy subjects (P = .021). A significantly higher level of plasma interleukin 4
      was noticed in patients with AAA than in healthy individuals (P = .008).
      CONCLUSIONS: This study suggests that RIG-I and TLR3 seem to be important factors
      in the pathogenesis of AAA.

PMID- 29567029
TI  - Through-knee amputation is a feasible alternative to above-knee amputation.
AB  - OBJECTIVE: Through-knee amputation (TKA) is a rare amputation performed in <2% of
      all major lower extremity amputations in the United States. Despite biomechanical
      benefits and improved rehabilitation compared with above-knee amputation (AKA),
      TKA has largely been abandoned by vascular surgeons because of concerns for poor
      wound healing. The purpose of this study was to evaluate surgical outcomes of
      TKA. METHODS: The American College of Surgeons National Surgical Quality
      Improvement Program between 2005 and 2012 was queried using Current Procedural
      Terminology codes indicating AKA and TKA. Baseline characteristics were reviewed,
      and logistic regression analysis was performed to identify predictors of 30-day
      mortality. Propensity score matching was used to balance comorbidities between
      AKA and TKA. Operative variables and postoperative complications were compared
      between the groups. RESULTS: A total of 7469 AKA and 251 TKA patients were
      identified among 15,932 major lower extremity amputations. Baseline
      characteristics were examined. White race, chronic obstructive pulmonary disease,
      dyspnea, emergent operation, steroid use, myocardial infarction, congestive heart
      failure, high American Society of Anesthesiologists score, old age, preoperative
      sepsis or septic shock, and dialysis dependency were associated with increased 30
      day mortality. Independent lifestyle and smoking (within 1 year) were protective
      against early death. Baseline comorbidities were not statistically significant
      after 1:1 propensity score matching. Operative outcomes were similar in both
      groups (AKA vs TKA). Wound infection (7.2% vs 11.2%; P = .16), dehiscence rate
      (1.2% vs 0.8%; P = 1.0), and 30-day mortality (9.6% vs 11.2%; P = .66) were
      comparable. Other outcome parameters, including cardiopulmonary and genitourinary
      complications, were similar except for a higher likelihood of return to the
      operating room in the TKA group (27.9% vs 12.4%; P < .01). Postoperative
      mortality was not associated with TKA (P = .77) or reoperation (P = .42), but it
      was associated with the patients' physiologic conditions (dyspnea, sepsis,
      emergent operation, high American Society of Anesthesiologists score, and
      dependent lifestyle). Predictors of reoperation were contaminated wound (hazard
      ratio [HR], 2.19; confidence interval [CI], 1.17-3.23; P = .015), sepsis or
      septic shock (HR, 2.63; CI, 1.37-5.05; P = .004), chronic obstructive pulmonary
      disease (HR, 2.81; CI, 1.23-6.42; P = .014), and wound infection (HR, 4.91; CI,
      2.06-11.70; P < .001). Presence of peripheral vascular disease was not associated
      with post-TKA reoperation (P = .073). CONCLUSIONS: TKA demonstrated similar
      postoperative morbidity and mortality compared with AKA. Wound infection and risk
      of dehiscence were equivalent. TKA did demonstrate a higher rate of reoperation;
      however, neither TKA nor reoperation predicted postoperative mortality. Patients
      in stable physiologic condition without active infection can safely undergo
      elective TKA to maximize rehabilitation potential.

PMID- 29567030
TI  - Comparison of 4 commercial kits for the extraction of circulating DNA from
      plasma.
AB  - The utility of circulating DNA as a source of clinical biomarkers in blood is
      limited by its low concentration and small fragment size. Effective purification
      methods can maximize circulating DNA yield and contribute to the success of
      downstream protocols. We describe the evaluation of 4 commercial DNA purification
      kits-QIAamp Circulating Nucleic Acids kit, QIAamp DNA Blood Mini kit, QIAamp
      Ultrasens Virus kit and the QIASymphony DSP Virus kit-for the extraction of high
      and low molecular weight DNA from blood plasma. Using qPCR to quantitate
      endogenous Alu sequences, as well as spiked exogenous high and low molecular
      weight zebrafish DNA, we found that the Circulating Nucleic Acids kit and the DSP
      kit were both efficient at purifying DNA from plasma regardless of fragment size,
      whereas the DNA Blood Mini kit was only able to effectively extract high
      molecular weight DNA. The Ultrasens Virus Kit produced the lowest yields for both
      large and small fragments. The use of carrier RNA with the Circulating Nucleic
      Acids and the DSP kits improved yields. Appropriate choice of kit can be an
      important factor in determining experiment outcome.

PMID- 29567031
TI  - Crisis of antibiotics: Health professionals, citizens and politicians, we are all
      responsible.

PMID- 29567032
TI  - The future control of rotavirus disease: Can live oral vaccines alone solve the
      rotavirus problem?
AB  - Live oral rotavirus (RV) vaccines used worldwide are most effective in reducing
      diarrheal hospitalizations from RV in high income countries and least effective
      in low income countries where RV remains a prime cause of death in children.
      Research has failed to fully explain the reason for this difference of efficacy
      for RV vaccines, an observation made with other live oral vaccines for polio,
      cholera and typhoid fever. Use of parenteral vaccines have been successful in
      overcoming this problem for both polio and typhoid and parenteral RV vaccines are
      now in development. This approach should be pursued for rotavirus vaccine as well
      because in low income countries where oral RV vaccines have been introduced and
      are only partially effective, RV remains the most common cause of diarrhea in
      children under 5 years. The ultimate control of RV diarrheal will likely require
      both oral and parenteral vaccines.

PMID- 29567033
TI  - Recombinant NADP-dependent isocitrate dehydrogenase of Edwardsiella tarda induces
      both Th1 and Th2 type immune responses and evokes protective efficacy against
      edwardsiellosis.
AB  - Edwardsiella tarda has become one of the most severe fish pathogens throughout
      the world. Thus, studies on the design and production of highly protective
      vaccines against this pathogen, as well as the mechanisms of vaccine-induced
      disease resistance are urgently needed. In this study, the NADP-dependent
      isocitrate dehydrogenase (IDH) of E. tarda was recombinantly expressed and
      flounder (Paralichthys olivaceus) anti-rIDH serum was prepared. Also, the outer
      membrane proteins (OMPs) of E. tarda were extracted and analyzed by western
      blotting. The results showed that flounder anti-rIDH serum could specifically
      recognize a 44 kDa protein of E. tarda OMPs, which was identified to be the
      native IDH of E. tarda by mass spectrometric. Consistently, immunogold electron
      microscopy showed that IDH could be detected on the membrane of E. tarda. Then,
      the vaccine potential of rIDH was tested in a flounder model, and the results
      showed that rIDH produced a relative percent survival (RPS) of 73.3%, which was
      significantly higher than that produced by formalin killed E. tarda cells.
      Immunological analysis showed that rIDH could induce the proliferation of rIDH
      specific sIg+ lymphocytes, which resulted in the production of anti-E. tarda
      antibodies. Accordingly, serum bactericidal activity assay showed that the serum
      of rIDH vaccinated fish exhibited the highest bactericidal activity compared with
      other groups. qRT-PCR analysis showed that rIDH could enhance the expressions of
      IFN-gamma, NKEF, IL-6, MHCIalpha, CD4-1 and CD8alpha. Moreover, the bacterial
      burden was also detected in vaccinated fish after challenge, which showed that
      the number of E. tarda cells in spleen of rIDH group was significantly lower than
      other groups. All these results suggested that rIDH is a promising vaccine
      candidate against E. tarda infection.

PMID- 29567034
TI  - Squalene containing solid lipid nanoparticles, a promising adjuvant system for
      yeast vaccines.
AB  - Potent adjuvant systems are required for subunit and single antigen based
      vaccines to provide sufficient immunogenicity. Furthermore, adjuvants can reduce
      the required number of immunisations and the antigen amount. Squalene
      nanoemulsions, like MF59(r) and AddaVaxTM, are potent, safe and well
      characterised adjuvant systems and approved for use in humans. Here, we developed
      squalene containing solid lipid nanoparticles, which can be sterilised by steam
      sterilisation and stored as freeze-dried power together with a yeast-based
      vaccine. Detailed size measurements using dynamic and static light scattering
      were applied, as the immune stimulating effect of squalene emulsions is mainly
      dependent on the particle size. The size range of AddaVaxTM (120-170 nm) was
      favoured for the developed squalene containing solid lipid nanoparticles.
      Differential scanning calorimetry (DSC) and H NMR studies were performed to
      characterise the interactions of the incorporated liquid squalene with the solid
      hard fat matrix. A homogeneous distribution as liquid domains in the solid
      glyceride structure was suggested for the liquid squalene. The developed adjuvant
      was compared with Freund's adjuvant and a commercially available squalene
      nanoemulsion in a vaccine trial in the mouse model with a yeast-based vaccine
      directed against the infectious bursal disease virus. All squalene-based
      adjuvants showed excellent biocompatibility and provided immune stimulating
      properties comparable to Freund's adjuvant.

PMID- 29567035
TI  - Knowledge, attitudes, and practices regarding hepatitis B vaccination among
      hospital-based doctors and nurses in China: Results of a multi-site survey.
AB  - BACKGROUND: Hepatitis B virus (HBV) can cause chronic HBV infection, which may
      lead to advanced cirrhosis and liver cancer. Healthcare workers (HCWs) are at
      risk HBV infection as an occupational hazard. Hepatitis B vaccination of HCWs is
      recommended by WHO, but the status of hepatitis B vaccination among HCWs in China
      is seldom reported. METHODOLOGY: We conducted a cross-sectional study in 22
      hospitals of 3 developed cities in China. We interviewed managers in infectious
      diseases and occupational health departments, and at least 40 HCWs per hospital.
      RESULTS: We interviewed 929 HCWs; 80.8% were vaccinated against hepatitis B and
      96.7% were willing to be vaccinated; 38.2% of HCWs reported having at least one
      needle stick or sharps injury. Three hospitals provide free hepatitis B
      vaccination for HCWs; hospitals with a hepatitis B vaccination policy, more HCWs
      reported being vaccinated (91.7% vs 79.0%, P < 0.001). HCWs in high risk
      departments (P = 0.011), with more knowledge of hepatitis B vaccine (P < 0.001),
      and with fewer working years (P = 0.002) were more likely to be vaccinated
      against HBV. Infectious diseases and occupational health managers had positive
      attitudes towards hepatitis B vaccination. CONCLUSIONS: Hepatitis B vaccination
      was well accepted among HCWs. Hospital provision of free vaccine, greater HCW
      knowledge of HBV, and working in higher-risk settings were associated with being
      vaccinated. A national policy of offering hepatitis B vaccine to HCWs should be
      considered in China. Provision of free hepatitis B vaccine for HBsAb negative
      HCWs may be acceptable. Education about HBV and hepatitis B vaccine may help
      promote policy implementation.

PMID- 29567037
TI  - Resurfacing hemiarthroplasty of the shoulder for patients with juvenile
      idiopathic arthritis.
AB  - BACKGROUND: This study reports the outcome of resurfacing hemiarthroplasty (RHA)
      in a cohort of patients with juvenile idiopathic arthritis (JIA) affecting the
      shoulder joint METHODS: Fourteen uncemented RHA procedures were performed for 11
      consecutive patients who required surgery because of JIA. Mean age at surgery was
      36.4 years. Mean clinical follow-up was 10.4 years (range, 5.8-13.9 years). A
      significant humeral head defect (up to 40% surface area) was found in 5 shoulders
      and filled with autograft from the distal clavicle or femoral head allograft.
      RESULTS: At latest follow-up, no patient required revision. There was excellent
      relief from pain. The mean Oxford Shoulder Score and Constant-Murley Score
      improved significantly. No shoulder had a poor outcome, and 6 had a very good or
      excellent outcome. Worse outcome was associated with an intraoperative finding of
      significant humeral head erosion. Two shoulders required early arthroscopic
      subacromial decompression, but there were no other reoperations. There were no
      instances of radiographic implant loosening or proximal migration. Painless
      glenoid erosion was seen in 5 shoulders but was not associated with worse
      outcome. CONCLUSIONS: The midterm results of RHA for JIA are at least comparable
      to those for stemmed hemiarthroplasty, with the added benefit of bone
      conservation.

PMID- 29567036
TI  - Fibrocartilaginous metaplasia identified in the long head of the biceps brachii.
AB  - BACKGROUND: In the glenohumeral joint, the long head of biceps brachii (LHBB) is
      exposed to tension and compression loading. The short head of biceps brachii
      (SHBB) works only in tension. It is known that tendon under compression might
      develop fibrocartilaginous metaplasia that improves the resistance to compression
      but reduces the resistance to tension. This study evaluated the presence of
      cartilage in LHBB and SHBB samples, supporting its possible role in tendon tear.
      METHODS: Between 2014 and 2016, 13 samples of LHBB and SHBB were collected during
      surgery for shoulder instability, glenohumeral arthritis, and massive rotator
      cuff tears. The samples were stained with hematoxylin and eosin, safranin-O, and
      Alcian blue (pH 1.0) for light microscopy. Immunohistochemistry was performed
      using anti-S100, anti-collagen I and II, and anti-tenascin-C antibodies. RESULTS:
      Histochemistry: LHBB samples showed matrix disorganization, with clusters of
      chondrocyte surrounded by collagen fibers and glycosaminoglycans. Safranin-O
      showed evident metachromasia. SHBB samples did not show any matrix
      disorganization or cartilaginous metaplasia. Immunohistochemistry: In all LHBB
      samples, anti-S100 and anti-collagen II showed cartilage in proximity of the
      tendon tear. Tenascin C immunostained closely to the disorganized matrix areas.
      SHBB, however, showed no positive areas for S-100, anti-collagen II, or tenascin
      C. CONCLUSIONS: According to our results, we hypothesize that the repeated
      stimulation in compression may induce the formation of fibrous cartilage.
      However, to date its role in tendon pathology remains to be clearly defined.

PMID- 29567038
TI  - Validating the Patient Reported Outcomes Measurement Information System (PROMIS)
      computerized adaptive tests for upper extremity fracture care.
AB  - BACKGROUND: Computerized adaptive testing (CAT) for patient-reported outcomes
      (PROs) is a developing area within orthopedic surgery. Our objective was to
      validate the Patient Reported Outcomes Measurement Information System (PROMIS)
      CATs for upper extremity fracture care. We sought to correlate PROMIS with legacy
      PROs and to investigate floor and ceiling effects. METHODS: Patients who
      underwent open reduction and internal fixation of upper extremity trauma were
      prospectively enrolled. Legacy PROs included the visual analog scale for pain,
      the Disabilities of the Arm, Shoulder and Hand questionnaire, the University of
      California-Los Angeles Shoulder Rating Scale, the Mayo Elbow Performance Score,
      and the 36-Item Short Form Health Survey. PROMIS CATs included Physical Function
      (PROMIS PF), PROMIS Pain Interference (PROMIS Pain), and PROMIS Upper Extremity
      (PROMIS UE). Correlations between the PROs were calculated as were the absolute
      and relative floor and ceiling effect. RESULTS: The study prospectively enrolled
      174 patients with upper extremity trauma. There was moderate to high correlation
      between PROMIS UE CAT and legacy upper extremity-specific PROs (rho = 0.42-0.79),
      and high correlation between the PROMIS PF CAT and the 36-Item Short Form Health
      Survey Physical Component Summary (rho = 0.71, P < .001). The visual analog scale
      for pain, University of California-Los Angeles Shoulder Rating Scale, Constant
      Score, and Mayo Elbow Score demonstrated a significant absolute ceiling effect
      (20.5%-23.7%), whereas the PROMIS PF, PROMIS UE, and PROMIS Pain CATs
      demonstrated no absolute ceiling effect. CONCLUSION: PROMIS PF, Pain, and UE
      correlate well with legacy PROs in a upper extremity trauma population, with less
      absolute floor or ceiling effects. This study provides preliminary evidence for
      the utility of PROMIS CATs in upper extremity trauma patients.

PMID- 29567039
TI  - Corrigendum to 'Extracorporeal Support During Bilateral Sequential Lung
      Transplantation in Patients with Pulmonary Hypertension: Risk factors and
      Outcomes' [Journal of Cardiothoracic and Vascular Anesthesia volume 31/2 (2017)
      418-425].

PMID- 29567040
TI  - Pro: Hyperoxia Should Be Used During Cardiac Surgery.

PMID- 29567041
TI  - Refractive error magnitude and variability: Relation to age.
AB  - PURPOSE: To investigate mean ocular refraction (MOR) and astigmatism, over the
      human age range and compare severity of refractive error to earlier studies from
      clinical populations having large age ranges. METHODS: For this descriptive study
      patient age, refractive error and history of surgery affecting refraction were
      abstracted from the Waterloo Eye Study database (WatES). Average MOR, standard
      deviation of MOR and astigmatism were assessed in relation to age. Refractive
      distributions for developmental age groups were determined. MOR standard
      deviation relative to average MOR was evaluated. Data from earlier clinically
      based studies with similar age ranges were compared to WatES. RESULTS: Right eye
      refractive errors were available for 5933 patients with no history of surgery
      affecting refraction. Average MOR varied with age. Children <1 yr of age were the
      most hyperopic (+1.79D) and the highest magnitude of myopia was found at 27yrs (
      2.86D). MOR distributions were leptokurtic, and negatively skewed. The mode
      varied with age group. MOR variability increased with increasing myopia. Average
      astigmatism increased gradually to age 60 after which it increased at a faster
      rate. By 85+ years it was 1.25D. J0 power vector became increasingly negative
      with age. J45 power vector values remained close to zero but variability
      increased at approximately 70 years. In relation to comparable earlier studies,
      WatES data were most myopic. CONCLUSIONS: Mean ocular refraction and refractive
      error distribution vary with age. The highest magnitude of myopia is found in
      young adults. Similar to prevalence, the severity of myopia also appears to have
      increased since 1931.

PMID- 29567042
TI  - Face and content validity of variables associated with the difficult-to-sedate
      child in the paediatric intensive care unit: A survey of paediatric critical care
      clinicians.
AB  - BACKGROUND: Clinicians recognise that some critically ill children are difficult
      to-sedate. It may be possible to identify this clinical phenotype for sedation
      response using statistical modelling techniques adopted from machine learning.
      This requires identification of a finite number of variables to include in the
      statistical model. OBJECTIVE: To establish face and content validity for 17
      candidate variables identified in the international literature as characteristic
      of the difficult-to-sedate child phenotype. METHODS: Paediatric critical care
      clinicians rated the relevance of 17 variables characterising the difficult-to
      sedate child using a four-point scale ranging from not (1) to highly relevant
      (4). Face and content validity of these variables were assessed by calculating a
      mean score for each item and computing an item-level content validity index.
      Items with a mean score >1 were rated as having adequate face validity. An item
      level content validity index >=0.70 indicated good to excellent content validity.
      SETTING AND PARTICIPANTS: Web-based survey emailed to members of the Pediatric
      Acute Lung Injury and Sepsis Investigators Network or the Society of Critical
      Care Medicine Pediatric Sedation Study Group. RESULTS: Of 411 possible
      respondents, 121 useable surveys were returned for a response rate of 29%. All
      items had a mean score >1, indicating adequate face validity. Ten of 17 items
      scored an item-level content validity index >=0.70. The highest scoring items
      were requiring three or more sedation classes simultaneously, daily modal
      sedation score indicating agitation, sedation score indicating agitation for 2
      consecutive hours, receiving sedatives at a dose >90th percentile of the usual
      starting dose, and receiving intermittent paralytic doses for sedation.
      CONCLUSIONS: Computation of an item-level content validity index validated
      variables to include in statistical modelling of the difficult-to-sedate
      phenotype. The results indicate consensus among paediatric critical care
      clinicians that the majority of candidate variables identified through literature
      review are characteristic of the difficult-to-sedate child.

PMID- 29567044
TI  - Reply.

PMID- 29567043
TI  - Intravital endoscopic technology for real-time monitoring of inflammation caused
      in experimental periodontitis.
AB  - We report a novel method for in situ imaging of microvascular permeability in
      inflamed gingival tissue, using state-of-the-art CellvizioTM intravital
      endoscopic technology and a mouse model of ligature-induced periodontitis. The
      silk ligature was first placed at the upper left second molar. Seven days later,
      the ligature was removed, and the animals were intravenously injected with Evans
      blue. Evans blue dye, which selectively binds to blood albumin, was used to
      monitor the level of inflammation by monitoring vascular permeability in control
      non-diseased and ligature-induced experimental periodontitis tissue. More
      specifically, leakage of Evans blue-bound albumin from the micro-capillary to
      connective tissue indicates the state of inflammation occurring in the specific
      site. Evans blue leakage from blood vessels was imaged in situ by directly
      attaching the endoscope (mini Z tip) of the CellvizioTM system to the gingival
      tissue without any surgical incision. Evans blue emission intensity was
      significantly elevated in gingiva of periodontitis lesions, but not control non
      ligature placed gingiva, indicating that this technology can be used as a
      potential minimally invasive diagnostic tool to monitor the level of inflammation
      at the periodontal disease site.

PMID- 29567045
TI  - Advancing the Science of Children's Positive Health in the National Institutes of
      Health Environmental Influences on Child Health Outcomes (ECHO) Research Program.

PMID- 29567046
TI  - An end-to-side suspender pancreaticojejunostomy: A new invagination
      pancreaticojejunostomy.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is a severe complication of
      the pancreaticoduodenectomy (PD). Recently, we introduced a method of suspender
      pancreaticojejunostomy (PJ) to the PD. In this study, we retrospectively analyzed
      various risk factors for complications after PD. We also introduced and assessed
      the suspender PJ to demonstrate its advantages. METHODS: Data from 335 patients
      with various periampullary lesions, who underwent the Whipple procedure (classic
      Whipple procedure or pylorus-preserving) PD by either traditional end-to-side
      invagination PJ or suspender PJ, were analyzed. The correlation between either
      perioperative or postoperative complications and corresponding PD approaches was
      evaluated by univariate analysis. RESULTS: A total of 147 patients received the
      traditional end-to-side invagination PJ, and 188 patients were given the
      suspender PJ. Overall, 51.9% patients had various complications after PD. The
      mortality rate was 2.4%. The POPF incidence in patients who received the
      suspender PJ was 5.3%, which was significantly lower than those who received the
      traditional end-to-side invagination PJ (18.4%) (P < 0.001). Univariate analysis
      showed that PJ approach and the pancreas texture were significantly associated
      with the POPF incidence rate (P < 0.01). POPF was a risk factor for both
      postoperative abdominal cavity infection (OR = 8.34, 95% CI: 3.99-17.42, P <
      0.001) and abdominal cavity hemorrhage (OR = 4.86, 95% CI: 1.92-12.33, P =
      0.001). CONCLUSIONS: Our study showed that the impact of the pancreas texture was
      a major risk factor for pancreatic leakage after a PD. The suspender PJ can be
      easily accomplished and widely applied and can effectively decrease the impact of
      the pancreas texture on pancreatic fistula after a PD and leads to a lower POPF
      incidence rate.

PMID- 29567047
TI  - Augmented reality technology for preoperative planning and intraoperative
      navigation during hepatobiliary surgery: A review of current methods.
AB  - BACKGROUND: Augmented reality (AR) technology is used to reconstruct three
      dimensional (3D) images of hepatic and biliary structures from computed
      tomography and magnetic resonance imaging data, and to superimpose the virtual
      images onto a view of the surgical field. In liver surgery, these superimposed
      virtual images help the surgeon to visualize intrahepatic structures and
      therefore, to operate precisely and to improve clinical outcomes. DATA SOURCES:
      The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were
      used for searching publications in the PubMed database. The primary source of
      literatures was from peer-reviewed journals up to December 2016. Additional
      articles were identified by manual search of references found in the key
      articles. RESULTS: In general, AR technology mainly includes 3D reconstruction,
      display, registration as well as tracking techniques and has recently been
      adopted gradually for liver surgeries including laparoscopy and laparotomy with
      video-based AR assisted laparoscopic resection as the main technical application.
      By applying AR technology, blood vessels and tumor structures in the liver can be
      displayed during surgery, which permits precise navigation during complex
      surgical procedures. Liver transformation and registration errors during surgery
      were the main factors that limit the application of AR technology. CONCLUSIONS:
      With recent advances, AR technologies have the potential to improve hepatobiliary
      surgical procedures. However, additional clinical studies will be required to
      evaluate AR as a tool for reducing postoperative morbidity and mortality and for
      the improvement of long-term clinical outcomes. Future research is needed in the
      fusion of multiple imaging modalities, improving biomechanical liver modeling,
      and enhancing image data processing and tracking technologies to increase the
      accuracy of current AR methods.

PMID- 29567048
TI  - [Central venous access for cancer chemotherapy].
AB  - The tip of a long term central venous access should be located at the junction of
      the superior vena cava with the right atrium in order to reduce the incidence of
      dysfunction and venous thromboses. Picc-lines have their place for treatments of
      less than 6 months with obvious advantages in terms of discretion and comfort.
      Long-term sequential chemotherapy is an indisputable indication of an implantable
      port, while long-term parenteral nutrition is an indication of a tunneled cuffed
      catheter. In case of mediastinal compression, the risk-benefit ratio favors
      femoral access. Catheter related venous thrombosis or infection do not
      necessarily require the withdrawal of the device. A device that is no longer used
      should be removed when the likelihood of recurrence of the disease is low or too
      far.

PMID- 29567049
TI  - Detection of Pathological Voice Using Cepstrum Vectors: A Deep Learning Approach.
AB  - OBJECTIVES: Computerized detection of voice disorders has attracted considerable
      academic and clinical interest in the hope of providing an effective screening
      method for voice diseases before endoscopic confirmation. This study proposes a
      deep-learning-based approach to detect pathological voice and examines its
      performance and utility compared with other automatic classification algorithms.
      METHODS: This study retrospectively collected 60 normal voice samples and 402
      pathological voice samples of 8 common clinical voice disorders in a voice clinic
      of a tertiary teaching hospital. We extracted Mel frequency cepstral coefficients
      from 3-second samples of a sustained vowel. The performances of three machine
      learning algorithms, namely, deep neural network (DNN), support vector machine,
      and Gaussian mixture model, were evaluated based on a fivefold cross-validation.
      Collective cases from the voice disorder database of MEEI (Massachusetts Eye and
      Ear Infirmary) were used to verify the performance of the classification
      mechanisms. RESULTS: The experimental results demonstrated that DNN outperforms
      Gaussian mixture model and support vector machine. Its accuracy in detecting
      voice pathologies reached 94.26% and 90.52% in male and female subjects, based on
      three representative Mel frequency cepstral coefficient features. When applied to
      the MEEI database for validation, the DNN also achieved a higher accuracy
      (99.32%) than the other two classification algorithms. CONCLUSIONS: By stacking
      several layers of neurons with optimized weights, the proposed DNN algorithm can
      fully utilize the acoustic features and efficiently differentiate between normal
      and pathological voice samples. Based on this pilot study, future research may
      proceed to explore more application of DNN from laboratory and clinical
      perspectives.

PMID- 29567050
TI  - The 2016 G. Paul Moore Lecture: Lessons in Voice Rehabilitation: Journal of Voice
      and Clinical Practice.
AB  - This Paul Moore Lecture honors the contributions made by authors to the Journal
      of Voice during a period of 30 years, from 1987. Fifty articles were selected and
      included under the following five topics: (1) normalcy of the larynx and voice;
      (2) the clinical speech-language pathologist's evaluation; (3) the patient's
      perspective; (4) the core of vocal rehabilitation; and (5) behavioral versus
      organic dysphonias. The analysis reflects a vivid landscape of the specific area
      and significant advances in knowledge. It also shows the valuable interdependence
      between science and clinical practice. The topics highlight the following
      information: (1) The physical appearance of a healthy larynx varies across
      individuals with normal voices. (2) The voice is not a binary descriptor (normal
      versus abnormal) but a variable measure, with many cultural influences on the
      perceptual auditory analysis of a voice. (3) The clinical speech-language
      pathologist assessment is multidimensional and multiparametric, with both
      subjective and objective analyses. The patients' opinion about the impact of a
      voice problem on his or her quality of life is significant when proposing a
      treatment. Therefore, it is also included in the initial assessment. (4) Vocal
      rehabilitation is a nonlinear process that combines direct and indirect
      approaches. Evidence of the positive effect of voice therapy is now well
      established. (5) Behavioral dysphonias may be linked to self-regulation of the
      use of voice and this needs to be taken into consideration. Although organic
      dysphonias are not necessarily the result of harmful vocal behaviors, they too
      can benefit from vocal rehabilitation.

PMID- 29567051
TI  - Effects of Therapy With Semi-occluded Vocal Tract and Choir Training on Voice in
      Adult Individuals With Congenital, Isolated, Untreated Growth Hormone Deficiency.
AB  - OBJECTIVES: Voice is produced by the vibration of the vocal folds expressed by
      its fundamental frequency (Hz), whereas the formants (F) are fundamental
      frequency multiples, indicating amplification zones of the vowels in the vocal
      tract. We have shown that lifetime isolated growth hormone deficiency (IGHD)
      causes high pitch voice, with higher values of most formant frequencies,
      maintaining a prepuberal acoustic prediction. The objectives of this work were to
      verify the effects of the therapy with a semi-occluded vocal tract (SOVTT) and
      choir training on voice in these subjects with IGHD. We speculated that acoustic
      vocal parameters can be improved by SOVTT or choir training. STUDY DESIGN: This
      is a prospective longitudinal study without control group. METHODS: Acoustic
      analysis of isolated vowels was performed in 17 adults with IGHD before and after
      SOVTT (pre-SOVTT and post-SOVTT) and after choir training (post training), in a
      30-day period. RESULTS: The first formant was higher in post training compared
      with the pre-SOVTT (P = 0.009). The second formant was higher in post-SOVTT than
      in pre-SOVTT (P = 0.045). There was a trend of reduction in shimmer in post-choir
      training in comparison with pre-SOVTT (P = 0.051), and a reduction in post-choir
      training in comparison with post-SOVTT (P = 0.047). CONCLUSIONS: SOVTT was
      relevant to the second formant, whereas choir training improved first formant and
      shimmer. Therefore, this speech therapy approach was able to improve acoustic
      parameters of the voice of individuals with congenital, untreated IGHD. This
      seems particularly important in a scenario in which few patients are submitted to
      growth hormone replacement therapy.

PMID- 29567052
TI  - The efficacy and safety of topical tranexamic acid: A systematic review and meta
      analysis.
AB  - Tranexamic acid (TXA) is an effective hemostatic agent used for the reduction of
      blood loss and transfusion. However, the safety profile of TXA remains in
      question due to a potential increased risk of venous thromboembolism. By applying
      TXA topically as opposed to intravenously, systemic absorption may be reduced and
      unwanted side-effects mitigated. The objective of our review is to investigate
      the efficacy and safety of topically applied tranexamic acid compared to both
      placebo, and the intravenous administration. Cochrane Central Register of
      Controlled Trials, MEDLINE, Embase, ISI Web of Science, PubMed, and
      Clinicaltrials.gov were searched from inception to November, 2016. We included
      randomized controlled trials that compared topical tranexamic acid to either
      placebo (or standard care) or intravenous administration, in adult patients.
      Surgical and non-surgical trials were included. Abstract, full-text selection,
      data extraction and risk of bias assessment were all performed in duplicate. In
      total, 67 studies involving 6,034 patients met inclusion criteria. The majority
      of trials evaluated orthopedic procedures. Compared to placebo, the
      administration of topical TXA significantly reduced the odds of receiving a blood
      transfusion (pooled OR 0.28, 95% CI 0.20 to 0.38; P < 0.001) and significantly
      reduced mean blood loss (WMD -276.6, 95% CI -327.8 to -225.4; P < 0.0001). When
      compared to the intravenous administration, there was no difference between the
      two groups in terms of transfusion requirements (pooled OR 1.03, 95% CI 0.72 to
      1.46; P=0.88) or blood loss (WMD -21.95, 95% CI -66.61 to 27.71; P=0.34). There
      was no difference in the odds of developing a venous thromboembolic complication
      between the topical TXA and control groups (pooled OR=0.78, 95% CI 0.47 to 1.29;
      P=0.33) or the topical and intravenous groups (pooled OR=0.75, 95% CI 0.39 to
      1.46; P=0.40). The topical application of TXA effectively reduces both
      transfusion risk and blood loss compared to placebo, without increasing
      thromboembolic risks. There were no major differences between topical and
      intravenous tranexamic acid with respect to safety and efficacy, and both were
      superior to placebo with regards to blood loss and transfusion requirements.
      Further study of the topical application is required outside of the field of
      orthopedics.

PMID- 29567053
TI  - Actinobacteria-Derived peptide antibiotics since 2000.
AB  - Members of the Actinobacteria, including Streptomyces spp., Kutzneria sp.
      Actinoplanes spp., Actinomycete sp., Nocardia sp., Brevibacteriumsp.,Actinomadura
      spp., Micromonospora sp., Amycolatopsis spp., Nonomuraea spp., Nocardiopsis spp.,
      Marinactinospora sp., Rhodococcus sp., Lentzea sp., Actinokineospora sp.,
      Planomonospora sp., Streptomonospora sp., and Microbacterium sp., are an
      important source of structurally diverse classes of short peptides of ~30
      residues or fewer that will likely play an important role in new antibiotic
      development and discovery. Additionally, many have unique structures that make
      them recalcitrant to traditional modes of drug resistance via novel mechanisms,
      and these are ideal therapeutic tools and potential alternatives to current
      antibiotics. The need for novel antibiotic is urgent, and this review summarizes
      199 Actinobacteria compounds published since 2000, including 35 cyclic
      lipopeptides containing piperazic or pipecolic acids, eight aromatic peptides,
      five glycopeptides, 21 bicyclic peptides, 44 other cyclic lipopeptides, five
      linear lipopeptides, six 2,5-diketopiperazines, one dimeric peptide, four
      nucleosidyl peptides, two thioamide-containing peptides, 25 thiopeptides, nine
      lasso peptides, and 34 typical cyclic peptides. The current and potential
      therapeutic applications of these peptides, including their structure,
      antituberculotic, antibacterial, antifungal, antiviral, anti-brugia, anti
      plasmodial, and anti-trypanosomal activities, are discussed.

PMID- 29567054
TI  - Electrical stimulation of the lower esophageal sphincter to address
      gastroesophageal reflux disease after sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) can result in de novo and
      worsen preexisting gastroesophageal reflux disease (GERD). Post-LSG patients with
      GERD refractory to proton pump inhibitors (PPI) usually undergo more invasive,
      anatomy-altering Roux-en-Y gastric bypass surgery. Lower esophageal sphincter
      (LES) electrical stimulation (ES) preserves the anatomy and has been shown to
      improve outcomes in GERD patients. OBJECTIVE: To evaluate the safety and efficacy
      of LES-ES in post-LSG patients with GERD not controlled with maximal PPI therapy.
      SETTING: Prospective, international, multicenter registry. METHODS: Patients with
      LSG-associated GERD partially responsive to PPI underwent LES-ES. GERD outcomes
      pre- and poststimulation were evaluated based on quality of life, esophageal acid
      exposure (after 6-12 mo), and PPI use. RESULTS: Seventeen patients (11 female,
      65%), treated at 6 centers between May 2014 and October, 2016 with a median
      follow-up of 12 months (range 6-24), received LES-ES. Median age was 48.6 years
      (interquartile range, 40.5-56), median body mass index 31.7 kg/m2 (27.9-39.3).
      All patients were on at least daily PPI preoperatively; at last follow-up, 7
      (41%) were completely off PPI, 5 (29%) took PPI on an intermittent basis, and 5
      (29%) were on single-dose PPI. Median GERD-health-related quality of life scores
      improved from 34 (on-PPI, 25-41) at baseline to 9 (6-13) at last follow-up (off
      PPI, P<.001). Percentage of time with esophageal pH<4 improved from 13.2% (3.7
      30.7) to 5.8% (1.1-54.4), P = .01. CONCLUSION: LES-ES in post-LSG patients
      suffering from symptomatic, PPI-refractory GERD resulted in significant
      improvement of GERD-symptoms, esophageal acid exposure, and need for PPI.
      Preserving the post-LSG anatomy, it offers a valid option for patients unable or
      unwilling to undergo Roux-en-Y gastric bypass surgery.

PMID- 29567055
TI  - Long-term follow-up of disease-specific quality of life after bariatric surgery.
AB  - BACKGROUND: Substantial improvements in health-related quality of life measured
      by generic questionnaires (most often the Short Form-36) have been noted over the
      long term in patients with morbid obesity who had undergone bariatric surgery.
      OBJECTIVES: To obtain long-term follow-up data on disease-specific quality of
      life in patients who underwent bariatric surgery (biliopancreatic diversion with
      duodenal switch) in 2007 to 2008. SETTING: Quebec Heart and Lung Institute,
      Quebec, Canada. METHODS: This study is a follow-up of the validation study, the
      Laval Questionnaire, an obesity-specific measure of health-related quality of
      life developed to be used in clinical trials. Patients who contributed to the
      validation study in 2007 to 2008 were administered the Laval Questionnaire again
      at long-term follow-up. RESULTS: Of 112 patients who contributed to the
      validation study, 90 were available for this long-term follow-up study (retention
      rate: 80%). Median follow-up was 8.8 years. For all 6 domains of the Laval
      Questionnaire, the improvements in quality-of-life scores were much larger than
      our best estimate of the minimal clinically important difference. In others, we
      observed some decline in quality-of-life scores over time after initial changes
      that occurred 1 to 2 years after surgery, during the so-called "honeymoon
      period." Improvements in quality of life were clearly related to surgery.
      CONCLUSION: This study confirms that bariatric surgery using biliopancreatic
      diversion with duodenal switch improves disease-specific quality of life in the
      short and long term. It also demonstrates that the Laval Questionnaire is
      responsive to treatment-induced changes.

PMID- 29567056
TI  - Psychological, behavioral, and weight-related aspects of patients undergoing
      reoperative bariatric surgery after gastric band: comparison with primary surgery
      patients.
AB  - BACKGROUND: Patients experiencing insufficient weight loss or weight regain in
      their first bariatric surgery may represent a high-risk group with greater
      problematic eating and general psychopathology levels, which may compromise the
      success of a reoperative procedure. OBJECTIVES: This study seeks to describe and
      compare disordered eating-related psychological and behavioral features of
      primary and reoperative surgery candidates after gastric band. SETTING: Hospital
      center and university in Portugal. METHODS: The baseline (preoperative) data from
      a longitudinal observational study are presented. Patients were interviewed by
      trained psychologists to identify binge-eating episodes and grazing and responded
      to a set of self-report measures: disordered eating, grazing, negative urgency,
      depression, anxiety, and stress. RESULTS: Two hundred twenty-five patients were
      undergoing primary surgery, and 166 were undergoing reoperative (REOP group)
      surgery. The groups did not differ in body mass index preoperatively, but the
      REOP group had greater weight suppression (t387 = -5.35, P = .001), higher
      highest (t387 = -3.40, P = .001) and lower lowest body mass index (t381 = 2.22, P
      = .03). The main reasons for reoperative surgery were weight regain/poor weight
      loss (42.8%) or medical complications (32.5%). REOP patients with objective binge
      eating reported a higher frequency of these episodes (t47 = 2.15, P = .04). No
      significant difference was found for the self-report measures assessed (only
      shape concern was higher for REOP group, F1,216 = 8.30, P<.001). CONCLUSIONS:
      Despite the preoperative similarities between patients undergoing reoperative or
      primary surgeries, the differences in binge eating and weight-related variables
      may associate with postoperative difficulties. The link between binge eating,
      weight suppression, and weight gain found in other samples suggests that patients
      undergoing reoperative surgery may be at increased risk for poor weight outcomes.

PMID- 29567057
TI  - Intraoperative analgesic regimen in laparoscopic bariatric surgery: a closer
      look.

PMID- 29567058
TI  - Increased circulating magnesium concentrations after Roux-en-Y gastric bypass
      surgery in patients with type 2 diabetes.
AB  - BACKGROUND: Low circulating magnesium concentrations predict cardiovascular and
      all-cause mortality in patients with type 2 diabetes (T2D). Epidemiologic and
      clinical studies have indicated lower extra- and intracellular magnesium
      concentrations in patients with diabetes. OBJECTIVE: We aimed to describe
      alterations, if any, in circulating magnesium concentrations after laparoscopic
      Roux-en-Y gastric bypass surgery (LRYGB) in patients with obesity and T2D.
      SETTING: Outpatient clinic of obesity and central hospital. METHODS:
      Retrospective analysis of 1-year outcome of plasma magnesium (p-Mg) and
      glucometabolic status in all consecutive patients who underwent primary LRYGBP
      and who completed the follow-up visits, including biochemical test panels 6 and
      12 months after surgery. RESULTS: LRYGBP and complete follow-up visits were
      performed in 51 patients with T2D and 86 patients without T2D. All patients were
      given similar dietary advice and multivitamin and mineral supplementation after
      surgery. Before RYGB, the patients with T2D showed lower p-Mg compared with
      patients without T2D (.79 +/- .06 mM and .82 +/- .05 mM, respectively, P<.01). P
      Mg was inversely correlated to fasting blood glucose and glycosylated hemoglobin
      levels. After surgery, mean p-Mg increased by 5.2% in the group with T2D compared
      with 1.4% in the patients without T2D (P<.01), ending at an equal level of .83
      mM. The alterations in p-Mg were inversely related to the changes in fasting
      glucose and glycosylated hemoglobin concentrations. CONCLUSION: The lowered p-Mg
      associated with impaired glucometabolic status in patients with T2D was increased
      after LRYGBP, reaching similar concentrations as in patients without T2D.

PMID- 29567059
TI  - Conversion of standard Roux-en-Y gastric bypass to distal bypass for weight loss
      failure and metabolic syndrome: 3-year follow-up and evolution of technique to
      reduce nutritional complications.
AB  - BACKGROUND: Standard proximal Roux-en-Y gastric bypass (RYGB) fails to achieve
      long-term weight maintenance and/or control of metabolic syndrome in up to 35% of
      patients. OBJECTIVES: To improve the performance of the standard proximal gastric
      bypass by increasing the biliopancreatic limb length at the expense of the common
      channel. SETTINGS: Academic-affiliated private practice. METHODS: A retrospective
      review of all patients who underwent conversion to distal RYGB from 2010 to 2016
      was performed. RYGB was modified by dividing the Roux limb at the
      jejunojejunostomy and transposing it distally to create a shortened total
      alimentary limb length (TALL) of 250 to 300 cm in the initial 11 patients. Of
      these, 7 developed protein calorie malnutrition and diarrhea requiring a second
      procedure to lengthen the common channel an additional 100 to 150 cm (TALL 400
      450 cm), leading to resolution of all symptoms. The subsequent 85 patients were
      converted to distal RYGB with TALL 400 to 450 in a single-stage operation.
      RESULTS: Ninety-six RYGB patients underwent conversion to distal RYGB. The mean
      body mass index and mean excess weight loss at the time of distalization was 40.6
      kg/m2 and 33.6%. At 1, 2, and 3 years after distalization, the mean body mass
      index was reduced to 34.4, 33.1, and 32.2 kg/m2, respectively, and excess weight
      loss improved to 41.9%, 53.7%, and 65.7%, respectively. Diabetes resolved in
      66.7%, hypertension resolved in 28.6%, hyperlipidemia resolved in 40%, and sleep
      apnea resolved in 50% at 1 year. The 30-day complication rate and reoperation
      rates were 6.3% and 5.2%; an additional 7.3% (7/96) required reoperation for limb
      lengthening. Hypoalbuminemia developed in 21% at 3 years, but no increase in iron
      deficiency was observed. Calcium metabolism was affected by the distalization
      procedure to a greater degree as 21% of patients had low corrected calcium
      levels, 77% were deficient in vitamin D, and parathyroid hormone levels were
      above normal in 64% at 3 years. CONCLUSION: Revision of proximal RYGB to distal
      RYGB results in substantial improvement in weight loss and resolution of co
      morbidities at 3 years. Diarrhea and protein calorie malnutrition were seen
      frequently in patients with TALL of 250 to 300 cm, whereas patients with TALL 400
      to 450 cm demonstrated a lower incidence of nutritional issues, but the effect on
      calcium, parathyroid hormone, and the fat soluble vitamins A and D is still a
      major concern.

PMID- 29567060
TI  - Laparoscopic sleeve gastrectomy as a viable option for an ambulatory surgical
      procedure: our 52-month experience.
AB  - BACKGROUND: We present our experience with same-day discharge (without an
      overnight stay) after laparoscopic sleeve gastrectomy (SG) in 821 consecutive
      patients from 2011 to 2015. This is the largest series published to date of
      patients undergoing ambulatory surgery for such a procedure. OBJECTIVES: To
      review our outcomes from ambulatory SG over 52 months to determine if SG can be
      safely performed in the ambulatory setting. SETTING: Ambulatory surgery center.
      METHODS: Retrospective review of all consecutive patients undergoing ambulatory
      SG from January 2011 to April 2015. All patients were discharged home the same
      day after surgery without an overnight stay at the hospital. Incidence of
      complications and admission to the hospital after discharge was reviewed up to 30
      days from surgery. RESULTS: From January 2011 to April 2015, 821 consecutive
      patients underwent SG. Nineteen 30-day complications occurred in the series, 17
      of them requiring admission to the hospital. Of the 19 cases, gastric leaks
      accounted for 7, intr-aabdominal abscess for 4, and dehydration/nausea/vomiting
      for 4; 4 were due to other causes. Complication and readmission rates at 30 days
      were 2.3% and 2.1%, respectively. Follow-up at 30 days was 98.4%. CONCLUSION:
      With stringent patient selection and utilization of enhanced recovery pathways,
      our study indicates that SG may be suitable for the outpatient setting.
      Experience and comfort with bariatric surgery is essential on the part of the
      operating surgeon to ensure good outcomes. Our low overall readmission and
      complication rate portends to the feasibility of laparoscopic SG as a safe
      outpatient procedure.

PMID- 29567061
TI  - Influence of stem length on component flexion and posterior condylar offset in
      revision total knee arthroplasty.
AB  - BACKGROUND: Hyperextension of the femoral component and excessive slope of the
      tibial component may delay the cam-post engagement in semi-constrained revision
      total knee arthroplasty (TKA). Further, it may compromise the posterior condylar
      offset (PCO). No prior study has determined whether a short 50-mm stem, or longer
      stems (100mm and 150mm) lead to less hyperextension of the femoral component or
      excessive slope and its influence on the posterior condylar offset. METHODS:
      Flexion/extension of the femoral component with respect to the sagittal femoral
      anatomic axis of the distal diaphysis (SFAA) and the tibial slope were measured
      from rotationally controlled lateral X-rays of 126 consecutive patients with a
      one- or two-stage revision TKA. Stems of 50mm, 100mm and 150mm were analyzed.
      Further, reconstruction of the PCO with respect to stem length and component
      flexion was evaluated. RESULTS: The average flexion (+) or extension (-) of the
      femoral component in the sagittal distal anatomical axis was -4.1 degrees +/-2.8
      degrees  (mean +/- std) for components, which have been implanted with 50-mm
      stems and 1.1 degrees +/-1.1 degrees  for components with 100- or 150-mm stems,
      respectively (P=0.0001). The average slope of the tibial was 2.6 degrees +/-1.5
      degrees  for tibial trays with 50-mm stems, which was more than the 1.3 degrees
      +/-1 degrees  for trays with 100-mm stems (P=0.0001). The average PCO ratio was
      0.8+/-1.7 for femoral components with 50-mm stems, which was less than the 1.0+/
      1.7 for trays with 100-mm stems (P=0.0001). CONCLUSIONS: Because 50-mm stems
      resulted in about three degree hyperextension of the femoral component with
      respect to the SFAA compared to 100-mm or 150-mm stems, the longer stems do not
      alter the natural femoral flexion and a delay of the cam-post engagement may be
      avoided. Further, a better reconstruction of the PCO may be archived with the use
      of longer stems.

PMID- 29567062
TI  - Time to Talk: Can Radiologists Improve Follow-Up of Abdominal Imaging Findings
      Indeterminate for Malignancy by Initiating Verbal Communication?
AB  - PURPOSE: The aims of this study were to examine the association between
      radiologist-initiated verbal communication for abdominal imaging findings
      indeterminate for malignancy and receipt of relevant outpatient follow-up imaging
      and to evaluate the proportion of findings that progress from indeterminate to
      suspicious for malignancy. METHODS: Using a mandatory standardized assessment
      coding system, 727 eligible outpatient abdominal CT, MRI, and ultrasound studies
      performed between July 1, 2013, and January 31, 2014, were identified.
      Multivariate logistic regression was used to evaluate the association between
      radiologist-initiated verbal communication and receipt of relevant outpatient
      imaging follow-up, adjusted for patient, ordering physician, interpreting
      radiologist, and imaging variables. RESULTS: Sixty-two percent of patients (451
      of 727) with imaging findings indeterminate for malignancy received relevant
      outpatient imaging follow-up. Radiologist-initiated verbal communication occurred
      in 4.8% of cases (35 of 727). Radiologist-initiated verbal communication (odds
      ratio [OR], 2.45; 95% confidence interval [CI], 1.02-5.87) and existing cancer
      diagnosis (OR, 3.00; 95% CI, 2.11-4.26) were associated with a higher likelihood
      of receiving relevant imaging follow-up. Compared with those whose imaging
      studies were ordered by clinicians in a medical specialty, patients with studies
      ordered by clinicians in surgical (OR, 0.70; 95% CI, 0.49-0.99) or other (OR,
      0.44; 95% CI, 20.24-0.83) specialties were less likely to receive relevant
      imaging follow-up. Progression of findings from indeterminate to suspicious for
      malignancy occurred in 5.4% of cases and was not associated with radiologist
      initiated verbal communication. CONCLUSIONS: Radiologist-initiated verbal
      communication increases the likelihood that patients receive outpatient imaging
      follow-up for abdominal findings indeterminate for malignancy. Progression of
      these findings is relatively infrequent.

PMID- 29567063
TI  - Robust qualitative estimation of time-varying contact rates in uncertain
      epidemics.
AB  - We will inevitably face new epidemics where the lack of long time-series data and
      the uncertainty about the outbreak dynamics make difficult to obtain quantitative
      predictions. Here we present an algorithm to qualitatively infer time-varying
      contact rates from short time-series data, letting us predict the start, relative
      magnitude and decline of epidemic outbreaks. Using real time-series data of
      measles, dengue, and the current zika outbreak, we demonstrate our algorithm can
      outperform existing algorithms based on estimating reproductive numbers.

PMID- 29567064
TI  - The distribution of district-level leprosy incidence in India is geometric
      stable, consistent with subcriticality.
AB  - Mathematical models predict that the community-level incidence of a controlled
      infectious disease across a region approaches a geometric distribution. This
      could hold over larger regions, if new cases remain proportional to existing
      cases. Leprosy has been disappearing for centuries, making an excellent candidate
      for testing this hypothesis. Here, we show the annual new case detection rate of
      leprosy in Indian districts to be consistent with a geometric distribution. For
      2008-2013, goodness-of-fit testing was unable to exclude the geometric, and the
      shape parameter of the best fit negative binomial distribution was close to unity
      (0.95, 95% CI 0.87-1.03). Ramifications include that a district-level cross
      sectional survey may reveal whether an infectious disease is headed towards
      elimination, that apparent outliers are expected and not necessarily
      representative of program failure, and that proportion 1/e of a small
      geographical unit may not meet a control threshold even when a larger area has.

PMID- 29567065
TI  - PINK1/Parkin-mediated mitophagy was activated against 1,4-Benzoquinone-induced
      apoptosis in HL-60 cells.
AB  - Hematotoxicity of benzene is derived mainly from its active metabolite, 1,4
      Benzoquinone (1,4-BQ), which induces cell apoptosis and mitochondrial damage.
      Damaged mitochondria are degraded through a specialized autophagy pathway, called
      mitophagy, which is driven by PINK1/Parkin signaling. However, whether mitophagy
      is involved in 1,4-BQ-induced toxicity remains unclear. This study was designed
      to investigate whether PINK1/Parkin-mediated mitophagy is activated in 1,4-BQ
      treated HL-60 cells, and the roles mitophagy plays in 1,4-BQ-induced apoptosis.
      Our results demonstrated that 1,4-BQ induced autophagy in HL-60 cells,
      characterized by increased LC3-II/LC3-I ratio and Beclin1 expression, as well as
      decreased expression of p62. We confirmed the presence of mitophagosomes using
      electron microscopy, and found that 1,4-BQ-induced autophagy was blocked by
      pretreatment with the mitophagy inhibitor Cyclosporine A (CsA). In addition, we
      found that 1,4-BQ induced mitochondrial stress through decreased mitochondrial
      membrane potential (MMP) and increasedproduction of reactive oxygen species
      (ROS). We also confirmed that 1,4-BQ-induced mitophagy was mediated by the
      PINK1/Parkin pathway, illustrated by increased expression of PINK1 and Parkin
      mRNA and protein. Finally, we examined 1,4-BQ-induced apoptosis with or without
      CsA, which demonstrated that apoptosis increased after mitophagy inhibition,
      suggesting that mitophagy has a protective effect in this context. In conclusion,
      this study demonstrates that the activated PINK1/Parkin-mediated mitophagy exerts
      a significantly protective effect against 1,4-BQ-induced apoptosis in HL-60
      cells.

PMID- 29567066
TI  - Correspondence: Leaflet thrombosis following transcatheter aortic valve
      implantation.

PMID- 29567067
TI  - How can NOX1 and ferritin be used as diagnostic and prognostic biomarkers in
      Parkinson's disease?

PMID- 29567068
TI  - Dynamics of the human gut phageome during antibiotic treatment.
AB  - Bacterial viruses contribute to the dynamics of the microbiome communities, as
      they are involved in the horizontal gene transfer. Previously we studied changes
      in the gut microbiome of the two healthy individuals over the course of a 6-days
      antibiotics treatment and subsequent 28 days recovery time (Willmann et al.,
      2015). Now, from the same samples, the virus-like particles were isolated and
      sequenced. As the phage sequences are currently poorly represented in reference
      databases, the reads had to be assembled, annotated and their abundance had to be
      evaluated via reads mapping. We analyzed and compared patterns of changes in
      abundance of the phage scaffolds and scaffolds with antibiotics resistant genes,
      in both phage and whole-genome metagenomic sets. We observed an increase in
      abundance of scaffolds carrying antibiotic-resistant genes in response to the
      treatment.

PMID- 29567069
TI  - The short-term presence of oleate or octanoate alters the phosphorylation status
      of Akt, AMPK, mTOR, CREB, and FoxO1 in liver of rainbow trout (Oncorhynchus
      mykiss).
AB  - We hypothesized that the presence of specific fatty acids modulate lipid
      metabolism in fish liver through changes in the phosphorylation status of
      proteins involved in cell signaling (Akt and mTOR) and cellular energy sensing
      (AMPK), and transcription factors (CREB and FoxO1). Therefore, we evaluated in
      pools of rainbow trout livers incubated for 3 h and 6 h at 15  degrees C in
      modified Hanks' medium containing 100 or 500 MUM oleate or octanoate, the
      response of these proteins. Our data confirm, for the first time in fish, that
      treatment of rainbow trout liver with oleate or octanoate resulted in the
      modulation of phosphorylation status of proteins involved in cell signaling
      (increased Akt and mTOR) and energy sensing (decreased AMPK), and in
      transcription factors (decreased CREB and increased FoxO1). The changes in these
      proteins occurred at the same time that changes in the mRNA abundance of several
      genes involved in lipid metabolism suggesting enhanced lipogenic potential
      (increased mRNA abundance of FAS, SREBP1c, and PPARalpha) and decreased
      mitochondrial activity (decreased UCP2a mRNA abundance) allowing us to suggest a
      relationship between both processes.

PMID- 29567070
TI  - Identification of duplicated Midkine genes and their functional regulation in
      blunt snout bream (Megalobrama amblycephala).
AB  - Midkine (Mdk) is a heparin-binding growth factor that is involved in regulating
      cell growth, differentiation and migration. Here, we report the isolation and
      characterization of duplicated mdk genes in blunt snout bream (Megalobrama
      amblycephala). The mdka and -b genes encode 146 aa and 147 aa peptides,
      respectively, sharing a sequence identity of 64%. During embryogenesis, mdka mRNA
      is detectable after 12 h post-fertilization (hpf) and mdkb mRNA can be detected
      after 8 hpf, about 4 h prior to mdka mRNA. Whole-mount in situ hybridization
      demonstrated that two paralogs of mdk mRNA were detected in the brain and dorsal
      neural tube at 16 hpf. At 22 hpf, mdka mRNA was abundant in the brain and dorsal
      neural tube, whereas mdkb mRNA were transcribed in the brain and tailbud. Later,
      at 55 hpf, both paralogs were mainly expressed in the brain. Furthermore, both
      the mdk genes were highly expressed in multiple adult tissues except in the skin
      and a low expression of mdka in the muscle. In addition, they were differentially
      inhibited in the liver and intestine with exogenous recombinant human growth
      hormone, while their mRNA levels were up-regulated in the brain. During
      starvation, both the mdk genes were significantly up-regulated in the intestine,
      brain and liver and returned to the control levels following 6 days of refeeding.
      Our results suggest that duplicated mdk genes may play conserved and divergent
      roles in embryonic development and tissue growth regulation in blunt snout bream.

PMID- 29567071
TI  - Predictive test for chemotherapy response in resectable gastric cancer: a multi
      cohort, retrospective analysis.
AB  - BACKGROUND: Adjuvant chemotherapy after surgery improves survival of patients
      with stage II-III, resectable gastric cancer. However, the overall survival
      benefit observed after adjuvant chemotherapy is moderate, suggesting that not all
      patients with resectable gastric cancer treated with adjuvant chemotherapy
      benefit from it. We aimed to develop and validate a predictive test for adjuvant
      chemotherapy response in patients with resectable, stage II-III gastric cancer.
      METHODS: In this multi-cohort, retrospective study, we developed through a multi
      step strategy a predictive test consisting of two rule-based classifier
      algorithms with predictive value for adjuvant chemotherapy response and
      prognosis. Exploratory bioinformatics analyses identified biologically relevant
      candidate genes in gastric cancer transcriptome datasets. In the discovery
      analysis, a four-gene, real-time RT-PCR assay was developed and analytically
      validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an
      internal cohort of 307 patients with stage II-III gastric cancer treated at the
      Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based
      chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used
      to evaluate the prognostic and chemotherapy response predictive value of the
      single patient classifier genes using associations with 5-year overall survival.
      The results were validated with a subset (n=625) of FFPE tumour samples from an
      independent cohort of patients treated in the CLASSIC trial (NCT00411229), who
      received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or
      surgery alone (n=302). The primary endpoint was 5-year overall survival.
      FINDINGS: We identified four classifier genes related to relevant gastric cancer
      features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier
      assay. In the validation cohort, the prognostic single patient classifier (based
      on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients
      as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5
      year overall survival for these groups was 83.2% (95% CI 75.2-92.0), 74.8% (69.9
      80.1), and 66.0% (60.1-72.4), respectively (p=0.012). The predictive single
      patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281
      (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group
      and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit
      group, 5-year overall survival was significantly improved in those patients who
      had received adjuvant chemotherapy after surgery compared with those who received
      surgery only (80% [95% CI 73.5-87.1] vs 64.5% [56.8-73.3]; univariate hazard
      ratio 0.47 [95% CI 0.30-0.75], p=0.0015), whereas no such improvement in 5-year
      overall survival was observed in the no-benefit group (72.9% [66.5-79.9] in
      patients who received chemotherapy plus surgery vs 72.5% [65.8-79.9] in patients
      who only had surgery; 0.93 [0.62-1.38], p=0.71). The predictive single patient
      classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant
      chemotherapy benefit in terms of 5-year overall survival in the validation cohort
      (pinteraction=0.036 in univariate analysis). Similar results were obtained in the
      internal evaluation cohort. INTERPRETATION: The single patient classifiers
      validated in this study provide clinically important prognostic information
      independent of standard risk-stratification methods and predicted chemotherapy
      response after surgery in two independent cohorts of patients with resectable,
      stage II-III gastric cancer. The single patient classifiers could complement TNM
      staging to optimise decision making in patients with resectable gastric cancer
      who are eligible for adjuvant chemotherapy after surgery. Further validation of
      these results in prospective studies is warranted. FUNDING: Ministry of ICT and
      Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health
      and Welfare.

PMID- 29567072
TI  - Precision medicine in the adjuvant treatment of gastric cancer.

PMID- 29567073
TI  - Diabetes duration, HbA1c, and cause-specific mortality in Mexico.

PMID- 29567074
TI  - Effect of diabetes duration and glycaemic control on 14-year cause-specific
      mortality in Mexican adults: a blood-based prospective cohort study.
AB  - BACKGROUND: Diabetes is a cause of at least a third of all deaths in Mexican
      adults aged 35-74 years, with the excess mortality due mainly to vascular
      disease, renal disease, infection, and acute diabetic crises. We aimed to analyse
      the effect of diabetes duration and glycaemic control on death rate ratios (RRs)
      for these causes and to assess the relevance to cause-specific mortality of
      undiagnosed diabetes. METHODS: About 100 000 women and 50 000 men aged 35 years
      or older from Mexico City were recruited into a blood-based prospective study
      between April 14, 1998, and Sept 28, 2004, and followed up until Jan 1, 2016, for
      cause-specific mortality. Participants who, at recruitment, reported any chronic
      disease other than diabetes and those who had missing data for HbA1c or diabetes
      duration were excluded. We used Cox models to estimate the associations of
      undiagnosed or previously diagnosed diabetes (almost all type 2) with risk of
      mortality from vascular disease, renal disease, and infection, exploring among
      those with previously diagnosed diabetes the independent relevance of diabetes
      duration (<5 years, >=5 to <10 years, or >=10 years) and HbA1c (<9%, >=9% to
      <11%, or >=11%). We also estimated the association of HbA1c with mortality in
      participants without diabetes at recruitment. FINDINGS: 133 662 participants were
      aged 35-74 years and had complete data and no other chronic disease. 16 940 (13%)
      had previously diagnosed diabetes, 6541 (5%) had undiagnosed diabetes, and 110
      181 (82%) had no diabetes. Among participants with previously diagnosed diabetes,
      glycaemic control was poor (median HbA1c 8.9% [IQR 7.0-10.9]), and was worse in
      those with longer duration of disease at recruitment. Compared with participants
      without diabetes, the death RRs at ages 35-74 years for the combination of
      vascular, renal, or infectious causes were 3.0 (95% CI 2.7-3.4) in those with
      undiagnosed diabetes, 4.5 (4.0-5.0) for the 5042 participants with a diabetes
      duration of less than 5 years, 6.6 (6.1-7.1) for the 7713 participants with a
      duration of 5 years to less than 10 years, and 11.7 (10.7-12.7) for the 4185
      participants with a duration of at least 10 years. Similarly, the death RRs were
      5.2 (4.8-5.7) for those with HbA1c less than 9%, 6.8 (6.2-7.4) for those with
      HbA1c of 9% to less than 11%, and 10.5 (9.7-11.5) for those with HbA1c of at
      least 11%. Diabetes was not strongly associated with the combination of deaths
      from other causes apart from acute glycaemic crises. Among participants without
      diabetes, higher HbA1c was not positively related to mortality. INTERPRETATION:
      In Mexico, the rates of death from causes strongly associated with diabetes
      increased steeply with duration of diabetes and were higher still among people
      with poor glycaemic control. Delaying the onset of type 2 diabetes, as well as
      improving its treatment, is essential to reduce premature adult mortality in
      Mexico. FUNDING: Wellcome Trust, the Mexican Health Ministry, the Mexican
      National Council of Science and Technology, Cancer Research UK, British Heart
      Foundation, and the UK Medical Research Council Population Health Research Unit.

PMID- 29567075
TI  - Astragaloside IV inhibits Angiotensin II-stimulated proliferation of rat vascular
      smooth muscle cells via the regulation of CDK2 activity.
AB  - AIMS: Astragaloside IV (AS-IV) is the central active component extracted from
      Radix astragali, an herbal remedy widely used in traditional Chinese medicine for
      the treatment of cardiovascular diseases. Aberrant proliferation of vascular
      smooth muscle cells (VSMCs) is closely involved in the initiation and progression
      of cardiovascular complications, such as atherosclerosis. Here we investigated
      whether AS-IV inhibited agonist-induced vascular smooth muscle cells (VSMCs)
      proliferation and the underlying mechanism. MAIN METHODS: Quiescent cultured A10
      cells (adult rat VSMCs) were treated with Angiotensin II (AngII) or AngII plus AS
      IV for 48 h. The growth rate of A10 cells was analyzed by CCK8 assay. RT-PCR
      analysis was carried out to examine the expression of alpha-smooth muscle actin
      (alpha-SMA), an important phenotypic modulation marker. In addition, whether the
      interference of AS-IV on AngII-mediated growth of VSMCs via regulation of cell
      cycle was evaluated by flow cytometry. In order to explore the role of cell cycle
      machinery, we measured kinase activity of CDK2 by Kinase assay and the protein
      level of Cdc25 by western blot, respectively. KEY FINDINGS: These data suggested
      that AS-IV exerted beneficial effects on AngII -induced abnormal growth in rat
      VSMCs through disturbing cell cycle, especially block G1/S transition by
      attenuating CDK2 activity, which may hinder the process of pathological vascular
      remodeling during atherosclerosis.

PMID- 29567076
TI  - Involvement of the nitric oxide in melatonin-mediated protection against injury.
AB  - Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and
      known well as an endogenous regulator of circadian and seasonal rhythms. It has
      been demonstrated that melatonin is involved in many physiological and
      pathophysiological processes showing antioxidant, anti-apoptotic and anti
      inflammatory properties. Nitric oxide (NO) is a free radical gas in the
      biological system, which is produced by nitric oxide synthase (NOS) family. NO
      acts as a biological mediator and plays important roles in different systems in
      humans. The NO/NOS system exerts a broad spectrum of signaling functions.
      Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system
      through multiple mechanisms that may influence physiological and
      pathophysiological processes. This article reviews the latest evidence for the
      effects of melatonin on NO/NOS regulation in different organs and disease
      conditions, the potential cellular mechanisms by which melatonin is involved in
      organ protection are discussed.

PMID- 29567077
TI  - Idiopathic pulmonary fibrosis (IPF) signaling pathways and protective roles of
      melatonin.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive loss of
      lung function due to tissue scarring. A variety of pro-inflammatory and pro
      fibrogenic factors including interleukin-17A, transforming growth factor beta,
      Wnt/beta-catenin, vascular endothelial growth factor, platelet-derived growth
      factor, fibroblast growth factors, endotelin-1, renin angiotensin system and
      impaired caveolin-1 function are involved in the IPF pathogenesis. Current
      therapies for IPF have some limitations and this highlights the need for
      effective therapeutic agents to treat this fatal disease. Melatonin and its
      metabolites are broad-spectrum antioxidants that not only remove reactive oxygen
      and nitrogen species by radical scavenging but also up-regulate the expression
      and activity of endogenous antioxidants. Via these actions, melatonin and its
      metabolites modulate a variety of molecular pathways in different
      pathophysiological conditions. Herein, we review the signaling pathways involved
      in the pathophysiology of IPF and the potentially protective effects of melatonin
      on these pathways.

PMID- 29567078
TI  - Beneficial role of biochanin A on cutaneous and renal tissues of ovariectomized
      rats treated with anastrozole.
AB  - AIMS: This study was designed to assess the beneficial role of biochanin A (BCA)
      in the protection of the cutaneous and renal tissues of ovariectomized rats, even
      in those treated with anastrozole (ANA). MATERIALS AND METHODS: For this purpose,
      60 adult female Wistar rats were allocated into 6 equal groups. Rats in group I
      (sham) underwent a sham operation and received distilled water orally. In groups
      II and III, OVX rats received either distilled water orally or DMSO
      intraperitoneally, respectively. In groups IV and V, OVX rats were either treated
      orally with 0.5 mg ANA/kg.b.wt. or administered 5 mg of BCA/kg.b.wt.
      intraperitoneally, respectively. In group VI (OVX-ANA-BCA), OVX rats were co
      treated with BCA and ANA. All treatments were given daily for 20 weeks. KEY
      FINDINGS: The IP administration of BCA significantly decreased serum levels of
      urea, creatinine, uric acid and MDA and significantly increased serum CAT, GSH
      and TAC and cutaneous IL-4 and GATA3 concentrations in the fifth and sixth groups
      compared to OVX-DMSO and OVX-ANA groups, respectively. Additionally, it induced
      down-regulation of renal TNF-alpha and iNOS expression as well as up-regulation
      of cutaneous TGF-beta expression. Furthermore, BCA ameliorated to variable
      degrees histological changes of renal and cutaneous tissue related to ovariectomy
      and/or ANA treatment. SIGNIFICANCE: These data suggest that BCA might be a useful
      alternative estrogen therapy for the management of renal and cutaneous changes
      observed in postmenopausal women, even in those treated with ANA.

PMID- 29567080
TI  - The Effect of Omega-3 on Circulating Adiponectin in Adults With Type 2 Diabetes
      Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
AB  - Whether consumption of omega-3 affects circulating adiponectin has not been
      established. The objective of this study was to evaluate the effect of omega-3
      (food or supplement) on circulating adiponectin in patients with type 2 diabetes
      through a systematic review of meta-analyses of randomized controlled trials.
      PubMed, Scopus and Web of Science were searched for relevant studies through May
      2016. Two researchers screened and abstracted the literature independently.
      Pooled estimates were obtained using the random-effects models. Overall, omega-3
      increased adiponectin by 0.57 ug/mL (95% confidence interval [CI] 0.15 to 1.31;
      p=0.01, I-square=74.2% p for heterogeneity <0.001). The source of observed
      heterogeneity was explored by subgroup analyses. In subgroup analyses,
      adiponectin levels increased only in those who had consumed omega-3 for more than
      8 weeks. This systematic review and meta-analysis of randomized, placebo
      controlled clinical trials suggests that omega-3 in patients with type 2 diabetes
      increases circulating adiponectin. These findings support the potentially
      beneficial effects of dietary omega-3 in patients with type 2 diabetes on
      pathways related to adiponectin metabolism.

PMID- 29567079
TI  - Early-Onset Physical Frailty in Adults With Diabesity and Peripheral Neuropathy.
AB  - OBJECTIVES: Diabesity (obesity and diabetes mellitus) has been identified as a
      potential contributor to early-onset frailty. Impairments contributing to early
      onset of physical frailty in this population are not well understood, and there
      is little evidence of the impact of peripheral neuropathy on frailty. The purpose
      of this study was to determine impairments that contribute to early-onset
      physical frailty in individuals with diabesity and peripheral neuropathy.
      METHODS: We studied 105 participants, 82 with diabesity and peripheral neuropathy
      (57 years of age, body mass index [BMI] 31 kg/m2); 13 with diabesity only (53
      years of age, BMI 34 kg/m2) and 10 obese controls (67 years of age, BMI 32
      kg/m2). Peripheral neuropathy was determined using Semmes Weinstein
      monofilaments; physical frailty was classified using the 9-item, modified
      Physical Performance Test; and knee extension and ankle plantarflexion peak
      torques were measured using isokinetic dynamometry. RESULTS: Participants with
      diabesity and peripheral neuropathy were 7.4 times more likely to be classified
      as physically frail. Impairments in lower-extremity function were associated with
      classification of frailty. CONCLUSIONS: Individuals with diabesity and peripheral
      neuropathy are particularly likely to be classified as frail. Earlier
      identification and interventions aimed at improving lower-extremity function may
      be important to mitigate the early-onset functional decline.

PMID- 29567082
TI  - Big tobacco turns its attention to Africa.

PMID- 29567081
TI  - Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against
      Pancreatic Carcinoma Metastases in a Phase 1 Trial.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell-mediated
      immunotherapy. We engineered T cells to transiently express a messenger RNA
      encoding a chimeric antigen receptor (CAR) specific for mesothelin, a protein
      that is overexpressed by PDAC cells. We performed a phase I study to evaluate the
      safety and efficacy of adoptive cell therapy with autologous mesothelin-specific
      CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory
      metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly
      for 3 weeks. None of the patients developed cytokine release syndrome or
      neurologic symptoms and there were no dose-limiting toxicities. Disease
      stabilized in 2 patients, with progression-free survival times of 3.8 and 5.4
      months. We used 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission
      tomography/computed tomography imaging to monitor the metabolic active volume
      (MAV) of individual tumor lesions. The total MAV remained stable in 3 patients
      and decreased by 69.2% in 1 patient with biopsy-proven mesothelin expression; in
      this patient, all liver lesions had a complete reduction in FDG uptake at 1 month
      compared with baseline, although there was no effect on the primary PDAC.
      Transient CAR expression was detected in patients' blood after infusion and led
      to expansion of new immunoglobulin G proteins. Our results provide evidence for
      the potential antitumor activity of messenger RNA CARTmeso cells, as well as PDAC
      resistance to the immune response.

PMID- 29567083
TI  - Bilateral simultaneous endoscopic carpal tunnel release: Mean time to resume
      activities of daily living and return to work.
AB  - : The purpose of this study was to determine the time needed to return to
      personal and professional activities after bilateral simultaneous endoscopic
      carpal tunnel release. During a retrospective, single-center study, we included a
      cohort of 30 patients (60 wrists). Patients were evaluated clinically (pain,
      paresthesia) and functionally (QuickDASH score) pre- and postoperatively. At the
      last follow-up, patients completed a questionnaire regarding the time needed to
      resume personal activities using the ADL scale (feeding, personal hygiene and
      dressing) and return to work. We also evaluated procedure satisfaction and
      willingness to undergo the surgery again. The average patient age was 60.5 years
      (range 39-86). At the last follow-up, average time to resume personal activities
      was 2.2 days (0-14) for feeding, 4.4 days (0-15) for personal hygiene and 3.9
      days (0-14) for dressing. Average time to return to recreational activities was
      11.7 days (1-60). Average time to return to work was 36.6 days (15-60). Overall,
      97% of patients were satisfied or very satisfied with the outcome. All patients
      would have the bilateral simultaneous surgery again. Bilateral simultaneous
      endoscopic carpal tunnel release is rarely performed. For mild conditions,
      contralateral symptom improvement is common after unilateral surgery. Bilateral
      simultaneous endoscopic carpal tunnel release appears to be disabling right after
      surgery, but clinical and functional scores are similar after the third
      postoperative day. These data can be used for patient education and decision
      making when considering surgery bilateral carpal tunnel syndrome. Bilateral
      simultaneous endoscopic carpal tunnel release is a feasible and safe procedure.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29567084
TI  - Aneurysms of the hand: Imaging and surgical technique.
AB  - Hand aneurysms are a rare entity only described as case reports in the
      literature. The aim of our study was to describe a series of four cases and the
      surgical technique using an arterial bypass. We also wanted to define an
      algorithm for the imaging of this pathology. We have operated on four patients
      with hand aneurysms in the past decade or so. One patient had an aneurysm in the
      thumb proper palmar digital artery, one in the superficial palmar arch and the
      two others in the ulnar artery. All patients had an excision surgery with direct
      arterial bypass; no patient had a venous graft. All patients were seen a few
      years after the surgery and underwent an ultrasonography to check the anastomosis
      permeability. All anastomoses were permeable 2 to 8 years after surgery. Through
      a review of the literature we discuss the best algorithm for imaging a hand
      aneurysm. Direct arterial suture by proximal and distal mobilization allows for
      long-term permeability. If a graft is necessary, a graft of arterial origin
      should be preferred. The additional first-line examination is ultrasonography,
      followed by arteriography if acute ischemia is present; otherwise, CT angiography
      or MR angiography is performed.

PMID- 29567085
TI  - Fixation of the nail plate by tension band suture versus 2-octyl-cyanoacrylate
      gluing for traumatic nail bed injuries reduced without suture: A retrospective
      study of 27 cases.
AB  - Repair of the nail bed and plate after distal phalanx trauma remains
      controversial. The aim of this study was to determine whether simple
      approximation of the nail bed flaps maintained by tension band suture of the nail
      plate is sufficient to prevent nail dystrophies. Our series gathered 27 fingers
      in 25 patients with a mean age of 36 years. In 15 cases (Group I), the nail plate
      was fixed in a single layer by a point in a frame, and in 12 cases (Group II),
      the bed and the plate were fixed layer-by-layer using the wound adhesive, 2
      octylcyanoacrylate. At the last follow-up, the Zook score was excellent and very
      good in 100% of Group I patients, and in 83.3% of Group II patients. Within 8
      days, the average pain was 1/10 in Group I, and 2.5/10 in Group II. There was one
      infection in Group I and four hematomas in Group II. The Quick DASH score was
      1.13/100 in Group I and 0 in Group II. Our results show that in the case of a
      traumatic nail bed injury, suturing the nail bed and applying 2
      octylcyanoacrylate adhesive is less effective than simple approximation of the
      nail bed flaps by tension band suture of the nail plate.

PMID- 29567086
TI  - Ultrasonographic evaluation of the distance between the flexor pollicis longus
      tendon and volar prominence of the plate as a function of volar plate positioning
      and pronator quadratus repair - A cadaver study.
AB  - Flexor tendon injury after volar plating of distal radius fractures is due to
      friction against the plate. To assess this risk, the distance between the flexor
      pollicis longus (FPL) and the volar prominence of the plate was measured with
      ultrasonography under various conditions: a standard plate fixed proximal or
      distal to the watershed line and a low-profile volar rim plate, with and without
      transection of the pronator quadratus (PQ). Distance from the FPL to the volar
      prominence of the plate decreased significantly when the PQ was cut and when a
      standard plate was placed distal to the watershed line, with the tendon often
      bulging over the plate. No statistical difference was measured between a volar
      rim plate and a standard plate distal to the watershed line. Our results confirm
      the importance of positioning the volar plate proximal to the watershed line and
      of repairing the PQ.

PMID- 29567087
TI  - A theoretical framework for the interpretation of pharmacist workforce studies
      throughout the world: The labor supply curve.
AB  - Despite geographic, financial, and cultural diversity, publications dealing with
      the pharmacist workforce throughout the world share common concerns and focus on
      similar topics. Their findings are presented in the literature in a seemingly
      unrelated way even though they are connected to one another as parts of a
      comprehensive theoretical structure. The purpose of this paper is to develop a
      theoretical model that relates some of the most salient topics addressed in the
      international literature on pharmacist workforce. The model is developed along
      two fundamental ideas. The first identifies the shape and location of the
      pharmacist's labor supply curve as the driving force behind all workforce
      decisions undertaken by pharmacists; the second argues that gender and age
      differences are two of the most important factors determining the shape and
      location of this supply curve. The paper then discusses movements along the curve
      attributed to changes in the wage rate, as well as displacements of the curve
      attributed to disparities in personal characteristics, investments in human
      capital, job-related preferences, opinions and perceptions, and institutional
      rigidities. The focus is on the individual pharmacist, not on groups of
      pharmacists or the profession as a whole. Works in multiple countries that
      address each topic are identified. Understanding these considerations is critical
      as employers' failure to accommodate pharmacists' preferences for work and
      leisure are associated with negative consequences not only for them but also for
      the healthcare system as a whole. Possible consequences include excessive job
      turnover, absenteeism, decreased institutional commitment, and lower quality of
      work.

PMID- 29567088
TI  - Community pharmacists' understanding and perceptions of FDA therapeutic
      equivalence standards.
AB  - BACKGROUND: Pharmacists need to demonstrate knowledge of and have confidence in
      Food and Drug Administration (FDA) therapeutic equivalence (TE) standards to
      improve acceptance of generic medicines amongst patients and other healthcare
      professionals. OBJECTIVE: To evaluate community pharmacists' understanding,
      interpretation and perceptions of the FDA TE standards to identify if further
      education is needed on this topic. METHODS: An anonymous, 13-item survey was
      piloted and then distributed by e-mail to a random sample of 287 Indiana
      community pharmacists. The 5-min survey included demographic, knowledge-based,
      and perception-based questions on FDA TE criteria that participants were given
      one week to complete. Participants completed the survey using a Web-based survey
      tool (Qualtrics). RESULTS: 192 pharmacists completed the survey achieving a
      response rate of 66.9%. Only 7.3% of respondents correctly identified FDA
      bioequivalence criteria for approval of generic drug products. Two questions
      presented TE codes from the Orange Book and asked respondents to identify if a
      pair of drug products were therapeutically equivalent: 62.6% and 61.0% of
      respondents answered correctly. However, 89.4% of respondents correctly indicated
      that the Orange Book is the location of FDA TE evaluations. 74.9% of responding
      pharmacists indicated a positive perception of the rigor of FDA approval
      standards associated with generic medications and 66.0% believed that generic
      drug products made by different manufacturers are of similar quality.
      CONCLUSIONS: The results suggest that community pharmacists need additional
      education on the interpretation of TE codes and FDA bioequivalence criteria for
      approval of generic drug products. The safety and efficacy of generics are often
      questioned by patients and physicians. It is important for pharmacists to be
      knowledgeable of FDA TE standards as they are experts in medicines and need to be
      confident with the criteria to effectively convey them to patients and healthcare
      professionals.

PMID- 29567089
TI  - An overview of the toxicities of checkpoint inhibitors in older patients with
      cancer.
AB  - Checkpoint inhibitors offer an exciting new option for treatment of a wide
      variety of cancers. By binding to surface receptors or their associated ligands
      on T cells, this class of drugs enhances immune activation and response to cancer
      cells. In available studies, the drugs are well tolerated, although toxicity
      involving skin, gastrointestinal tract, liver, lungs, and endocrine organs has
      been observed. Unfortunately, few studies to date have included patients older
      than 70 years of age. Since aging has been linked to changes in immune function,
      there are theoretical concerns that this patient population might experience a
      different profile of adverse events. This article reviews the tolerability of
      checkpoint inhibitors in older patients with cancer in clinical practice.

PMID- 29567091
TI  - Non-contrast MDCT for Ureteral Calculi and Alternative Diagnoses: Yield in Adult
      Women vs in Adult Men.
AB  - PURPOSE: To determine the yield of non-contrast multi-detector computed
      tomography (MDCT) of the abdomen and pelvis in diagnosing ureteral calculi as
      well as other alternative acute conditions in male vs in female adult patients
      presenting to the emergency department with new onset of symptoms. METHODS: Our
      institutional review board approved a retrospective review of the official
      reports of the non-contrast MDCT examinations of the abdomen and pelvis performed
      on adults (18 years and older) presenting to our emergency department with a
      suspected ureteral calculus from October 1, 2011 to October 30, 2013. Patients
      with recently documented ureteral calculi, known urinary tract infection,
      malignancy, and trauma were excluded from the study. From a total of 1097 non
      contrast MDCT examinations of the abdomen and pelvis over the 2-year period, 400
      randomly selected examinations were reviewed (approximately one-third of all the
      examinations). We compared the prevalence of ureteral calculi between the male
      and female population. P values and confidence intervals were determined using
      software Stata 14. Other acute intra-abdominal and intra-pelvic findings amenable
      to prompt medical care were also documented and analyzed separately. RESULTS: The
      mean patient age was 55.2 years, with a range of 19-90 years. This included 170
      female (mean age 56.8 years) and 230 male patients (mean age 54.2 years).
      Ureteral calculi were detected in 170 (42.5%) of the patients [111 males (48%)
      and 59 females (34.7%)] with a prevalence which was statistically significantly
      higher in the male patients compared to in the female patients (P < 0.01,
      confidence level of 95% and CI of 13.2-13.4). An alternative diagnosis was made
      based on the MDCT findings in 49 patient cases (12.25 %), including 26 females
      (15.29%) and 23 males (10.00%). There was no statistically significant difference
      in alternative acute findings in male compared to in female patients (P > 0.05).
      This was with the exception of acute pyelonephritis, which was statistically
      significantly higher in the female patients (P < 0.01). CONCLUSION: The
      likelihood of making the diagnosis of a ureteral calculus on non-contrast MDCT of
      the abdomen and pelvis was statistically significantly higher in male patients
      compared with female patients presenting to our emergency department. However,
      there was no statistically significant difference in the alternative diagnoses,
      with the exception of pyelonephritis, which was more common in women.

PMID- 29567090
TI  - Quantitation of myosin regulatory light chain phosphorylation in biological
      samples with multiple reaction monitoring mass spectrometry.
AB  - The 20-kDa regulatory light chain of myosin II plays an important role in
      regulating smooth muscle contractile force. LC20 is phosphorylated canonically by
      myosin light chain kinase in a Ca2+/calmodulin-dependent manner at S19. The
      diphosphorylation of LC20 at T18 and S19 has been observed in smooth muscle
      tissues. Given that the phosphorylation of LC20 is positively correlated with
      tension development, the molar stoichiometry of LC20 phosphorylation is commonly
      profiled as a measure of smooth muscle contractility. Herein, we describe a novel
      multiple reaction monitoring (MRM)-mass spectrometry (MS) approach for the
      quantification of LC20 phosphorylation at T18 and S19. Unique precursor as well
      as y- and b-ion transitions were identified for unphosphorylated LC20-(TS),
      monophosphorylated LC20-(TpS) and diphosphorylated LC20-(pTpS) peptides. The MRM
      MS assay could accurately define molar phosphorylation stoichiometries of S19 and
      T18 over a broad range (i.e., 0-2 mol P/mol LC20). Correlations of the results
      for two quantification techniques indicate that the MRM-MS assay performs equally
      to Phos-tag SDS-PAGE for the determination of LC20 phosphorylation stoichiometry
      in arterial tissue samples. The MRM-MS technique provides a robust alternative to
      antibody-based detection systems for the quantification of LC20 phosphorylation.

PMID- 29567092
TI  - Nucleus accumbens GLT-1a overexpression reduces glutamate efflux during
      reinstatement of cocaine-seeking but is not sufficient to attenuate
      reinstatement.
AB  - Cocaine use disorder is a chronically relapsing disease without FDA-approved
      treatments. Using a rodent model of cocaine relapse, we and others have
      previously demonstrated that the beta-lactam antibiotic ceftriaxone attenuates
      cue- and cocaine-primed reinstatement of cocaine-seeking. Ceftriaxone restores
      cocaine-induced deficits in both system xc- and GLT-1 expression and function in
      the nucleus accumbens core (NAc). We recently demonstrated that restoration of
      GLT-1 expression in the NAc is necessary for ceftriaxone to attenuate
      reinstatement of cocaine-seeking. Here we used an adeno-associated virus (AAV) to
      overexpress GLT-1a in the NAc to investigate whether such restoration is
      sufficient to attenuate cue- and cocaine-primed reinstatement. Rats self
      administered cocaine for two weeks and received injections of either AAV-GFAP-GLT
      1a or AAV-GFAP-eGFP in the NAc following the last day of self-administration.
      Rats then underwent three weeks of extinction training (during which time
      transduction and expression occurred) before undergoing a cue- or cocaine-primed
      reinstatement test. Microdialysis for the quantification of glutamate efflux in
      the NAc was conducted during the cocaine-primed test. Rats that received AAV-GFAP
      GLT-1a reinstated cue-primed cocaine-seeking in a similar manner as rats that
      received the control AAV-GFAP-eGFP. Upregulation of GLT-1a attenuated glutamate
      efflux during a cocaine-primed reinstatement test, but was not sufficient to
      attenuate reinstatement. We confirmed that GLT-1a upregulation resulted in
      functional upregulation of glutamate transport and expression, without affecting
      sodium-independent glutamate uptake, indicating system xc-was not altered. These
      results indicate that upregulation of NAc GLT-1 transporters alone is not
      sufficient to prevent the reinstatement of cocaine-seeking and implicate
      additional mechanisms in regulating glutamate efflux.

PMID- 29567093
TI  - N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice.
AB  - Cigarette smokers with brain damage involving the insular cortex display
      cessation of tobacco smoking, suggesting that this region may contribute to
      nicotine addiction. In the present study, we speculated that molecules in the
      insular cortex that are sensitive to experimental traumatic brain injury (TBI) in
      mice might provide leads to ameliorate nicotine addiction. Using targeted
      lipidomics, we found that TBI elicited substantial increases of a largely
      uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular
      cortex of mice. We then evaluated whether intraperitoneal administration of OlGly
      would alter withdrawal responses in nicotine-dependent mice as well as the
      rewarding effects of nicotine, as assessed in the conditioned place preference
      paradigm (CPP). Systemic administration of OlGly reduced mecamylamine
      precipitated withdrawal responses in nicotine-dependent mice and prevented
      nicotine CPP. However, OlGly did not affect morphine CPP, demonstrating a degree
      of selectivity. Our respective in vitro and in vivo observations that OlGly
      activated peroxisome proliferator-activated receptor alpha (PPAR-alpha) and the
      PPAR-alpha antagonist GW6471 prevented the OlGly-induced reduction of nicotine
      CPP in mice suggests that this lipid acts as a functional PPAR-alpha agonist to
      attenuate nicotine reward. These findings raise the possibility that the long
      chain fatty acid amide OlGly may possess efficacy in treating nicotine addiction.

PMID- 29567094
TI  - Antimicrobial resistance in aquaculture: Current knowledge and alternatives to
      tackle the problem.
AB  - Aquaculture is a rapidly growing industry that currently accounts for almost half
      of the fish used for human consumption worldwide. Intensive and semi-intensive
      practices are used to produce large stocks of fish, but frequent disease
      outbreaks occur, and the use of antimicrobials has become a customary practice to
      control them. The selective pressure exerted by these drugs, which are usually
      present at sub-therapeutic levels for prolonged periods in the water and the
      sediments, provides ideal conditions for the emergence and selection of resistant
      bacterial strains and stimulates horizontal gene transfer. It is now widely
      recognized that the passage of antimicrobial resistance genes and resistant
      bacteria from aquatic to terrestrial animal husbandry and to the human
      environment and vice versa can have detrimental effects on both human and animal
      health and on aquatic ecosystems. A global effort must be made to cease
      antimicrobial overuse in aquaculture and encourage stakeholders to adopt other
      disease-prevention measures. Shaping a new path is crucial to containing the
      increasing threat of antimicrobial resistance.

PMID- 29567095
TI  - Antioxidant-based synergistic eradication of methicillin-resistant Staphylococcus
      aureus (MRSA) biofilms with bacitracin.
AB  - Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) have serious
      clinical implications. However, it is difficult to eradicate MRSA biofilms due to
      the increased tolerance to antimicrobials of biofilms. In this study, we
      investigated the synergistic anti-biofilm effect of the combination of octyl
      gallate (OG), an antioxidant approved by the US Food and Drug Administration
      (FDA) as a food additive, and bacitracin, an antimicrobial peptide commonly used
      in topical antimicrobial ointments. The results of biofilm assays showed that OG
      enabled bacitracin at concentrations as low as 10-3 U/ml to inhibit biofilm
      formation in MRSA. A confocal microscopic analysis exhibited that the combination
      of bacitracin and OG suppressed biofilm formation in MRSA highly effectively
      compared to the single treatment of either bacitracin or OG. The synergistic anti
      biofilm activity of bacitracin and OG was also confirmed in MRSA strains from
      humans, including USA300, which is the predominant clone of community-associated
      MRSA in the US. To the best of our knowledge, this is the first report about the
      synergistic anti-biofilm activity of an antimicrobial peptide and an antioxidant
      against MRSA.

PMID- 29567096
TI  - Heterogeneity among splanchnic vein thrombosis associated with myeloproliferative
      neoplasms.

PMID- 29567097
TI  - Differential neural responses to faces paired with labels versus faces paired
      with noise at 6- and at 9-months.
AB  - Labeling objects or faces in the first year of life shapes subsequent attention
      and perception. Three months of hearing individual-level, unique labels for
      previously unfamiliar faces promotes face differentiation and impacts neural
      processing during the first year of life. However, it is currently unclear
      whether verbal labeling influences visual processing of faces during label
      learning and whether these effects differ across the first year of life. The
      current study examined the impact of individual-level labels versus a non-speech
      noise on neural responses to monkey faces. Event-related potentials (ERPs) were
      recorded while infants viewed two species of monkey faces: one paired with labels
      and one paired with a non-speech noise. At 9 months, neural responses
      differentiated monkey faces paired with labels relative to those paired with
      noise during both the first and second halves of the experiment. Nine-month-olds
      exhibited a faster P1 latency, marginally greater N290 amplitude and reduced P400
      amplitude to labeled faces relative to a non-speech noise. However, 6-month-olds'
      neural responses did not differentiate monkey faces paired with labels from those
      paired with a non-speech noise until the second half of trials and only showed
      this effect for P1 latency and N290 amplitude. The results of this study suggest
      that overall, infants differentiate faces labeled with individual-level labels
      from those paired with a non-speech noise, however, 6-month-olds require more
      exposure to the label-face pairings than 9-month-olds.

PMID- 29567098
TI  - External and internal facial features modulate processing of vertical but not
      horizontal spatial relations.
AB  - Some years ago an asymmetry was reported for the inversion effect for horizontal
      (H) and vertical (V) relational face manipulations (Goffaux & Rossion, 2007).
      Subsequent research examined whether a specific disruption of long-range
      relations underlies the H/V inversion asymmetry (Sekunova & Barton, 2008). Here,
      we tested how detection of changes in interocular distance (H) and eye height (V)
      depends on cardinal internal features and external feature surround. Results
      replicated the H/V inversion asymmetry. Moreover, we found very different face
      cue dependencies for both change types. Performance and inversion effects did not
      depend on the presence of other face cues for detecting H changes. In contrast,
      accuracy for detecting V changes strongly depended on internal and external
      features, showing cumulative improvement when more cues were added. Inversion
      effects were generally large, and larger with external feature surround. The cue
      independence in detecting H relational changes indicates specialized local
      processing tightly tuned to the eyes region, while the strong cue dependency in
      detecting V relational changes indicates a global mechanism of cue integration
      across different face regions. These findings suggest that the H/V asymmetry of
      the inversion effect rests on an H/V anisotropy of face cue dependency, since
      only the global V mechanism suffers from disruption of cue integration as the
      major effect of face inversion.

PMID- 29567099
TI  - Short and long-term visual deprivation leads to adapted use of audiovisual
      information for face-voice recognition.
AB  - Person identification is essential for everyday social interactions. We quickly
      identify people from cues such as a person's face or the sound of their voice. A
      change in sensory input, such as losing one's vision, can alter how one uses
      sensory information. We asked how people with only one eye, who have had reduced
      visual input during postnatal maturation of the visual system, use faces and
      voices for person identity recognition. We used an old/new paradigm to
      investigate unimodal (visual or auditory) and bimodal (audiovisual) identity
      recognition of people (face, voice and face-voice) and a control category,
      objects (car, horn and car-horn). Participants learned the identity of 10 pairs
      of faces and voices (Experiment 1) and 10 cars and horns (Experiment 2) and were
      asked to identify the learned face/voice or car/horn among 20 distractors. People
      with one eye were more sensitive to voice identification compared to controls
      viewing binocularly or with an eye-patch. However, both people with one eye and
      eye-patched viewing controls use combined audiovisual information for person
      identification more equally than binocular viewing controls, who favour vision.
      People with one eye were no different from controls at object identification. The
      observed visual dominance for binocular controls is larger for person compared to
      object identification, indicating that faces (vision) play a larger role in
      person identification and that person identity processing is unique from that for
      objects. People with long-term visual deprivation from the loss of one eye may
      have adaptive strategies, such as placing less reliance on vision to achieve
      intact performance, particularly for face processing.

PMID- 29567100
TI  - Force-velocity profiling in older adults: An adequate tool for the management of
      functional trajectories with aging.
AB  - INTRODUCTION: The actual mechanisms leading to a reduced muscle power and
      functional ability in older adults are poorly understood. We investigated the
      association between different force-velocity (F-V) profiles and impaired muscle
      power, physical and cognitive function, frailty, and health-related quality of
      life (HRQoL) in older people. METHODS: Physical function (habitual gait speed,
      timed up-and-go test, sit-to-stand and stair-climbing ability), cognitive
      function, HRQoL and frailty were evaluated in 31 older subjects (70-85 years).
      The F-V relationship and maximal muscle power (Pmax) were assessed in the leg
      press exercise. The skeletal muscle index (SMI) and fat index, moderate-to
      vigorous physical activity (MVPA) and sedentary time were obtained from DXA scans
      and accelerometry, respectively. RESULTS: While some subjects showed a force
      deficit (FDEF), others presented a velocity deficit (VDEF), both leading to an
      impaired muscle power [Effect size (ES) = 1.30-1.44], and to a likely-very likely
      moderate harmful effect in their physical and cognitive function, HRQoL and
      frailty levels (except the VDEF group for cognitive function) [ES = 0.76-1.05].
      Leg muscle mass and specific force were similarly associated with force at Pmax,
      while MVPA but not sedentary time was related to fat index, force at Pmax, and
      power values (all p < 0.05). A trend was found for the negative association
      between fat index and relative Pmax (p = 0.075). CONCLUSION: Older subjects
      exhibited different mechanisms (force vs. velocity deficits) leading to impaired
      muscle power. Both deficits were associated with a lower physical function and
      quality of life, and a higher frailty, whereas only a force deficit was
      associated with a lower cognitive function. Interventions aimed at reversing age-
      and/or disuse-related impairments of muscle power might evaluate the specific
      responsible mechanism and act accordingly.

PMID- 29567101
TI  - NaHS restores mitochondrial function and inhibits autophagy by activating the
      PI3K/Akt/mTOR signalling pathway to improve functional recovery after traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is one of the most serious public health problems in
      the world. TBI causes neurological deficits by triggering secondary injuries.
      Hydrogen sulfide (H2S), a gaseous mediator, has been reported to exert
      neuroprotective effects in central nervous system diseases, such as TBI. However,
      the molecular mechanisms involved in this effect are still unclear. The present
      study was designed to explore the ability of NaHS, a H2S donor, to provide
      neuroprotection in a mouse model of TBI and to discover the associated molecular
      mechanisms of these protective effects. Here, we found that administration of
      NaHS not only maintained the integrity of the blood brain barrier (BBB),
      protected neurons from apoptosis, and promoted remyelination and axonal
      reparation but also protected mitochondrial function. In addition, we found that
      autophagy was inhibited after treatment with NaHS following TBI, an effect that
      was induced by activation of the PI3K/AKT/mTOR signalling pathway. Our study
      indicated that H2S treatment is beneficial for TBI, pointing to H2S as a
      potential therapeutic target for treating TBI.

PMID- 29567102
TI  - A direct determination of AFBs in vinegar by aptamer-based surface plasmon
      resonance biosensor.
AB  - Aflatoxin (AFB) is one of the most toxic fungal metabolites produced by
      Aspergillus flavus, which may contaminate food and agricultural products. Herein,
      an aptamer-based surface plasmon resonance (SPR) biosensor was developed to
      detect AFBs. The chosen aptamer showed comparable interaction with the two AFBs,
      namely aflatoxin B1 (AFB1) and aflatoxin B2 (AFB2). Such phenomenon was rarely
      reported, and might lead to a simultaneous detection of both AFBs. In this study,
      AFB1 was used to systematically establish the detection method. In the SPR
      system, streptavidin proteins were immobilized on the surface of a CM5 sensor
      chip as a cross-linker and biotin-aptamers were captured through streptavidin
      biotin interaction. After optimization, the assay showed a dynamic range between
      0.09 and 200 ng mL-1 (linear range from 1.5 to 50 ng mL-1 and a LOD of 0.19 ng mL
      1) of AFB1 in buffer. As expected, the aptasensor showed high specificity towards
      AFB1 and AFB2, but hardly bound to other toxins with similar structures,
      including ochratoxin A (OTA), ochratoxin B (OTB), Zeralenone (ZEA) and T-2 toxin
      (T-2). Determination of AFB1 in vinegar was further performed using the SPR
      biosensor. Recoveries of AFB1 from spiked samples ranged from 96.3 to 117.8%. The
      developed SPR assay is a simple, fast and sensitive approach for the detection of
      residual AFBs in agricultural products and foodstuffs like vinegar.

PMID- 29567103
TI  - Analysis of snake venom metalloproteinases from Myanmar Russell's viper
      transcriptome.
AB  - Snake venom metalloproteinases (SVMPs) are the key enzymes in Russell's viper
      (RV) venom which target all important components of haemostasis, such as clotting
      factors, platelets, endothelial cells and basement membrane. The structural
      diversity of SVMPs contributes to the broad spectrum of biological activities.
      The aim of the study was to investigate the SVMP transcript profile to gain
      better insights into the characteristic clinical manifestations of the Myanmar
      Russell's viper (MRV) bites that distinguish it from the RVs of other habitats.
      Next generation sequencing (RNA-Seq) of mRNA from MRV venom glands (2 males and 1
      female) was performed on an Illumina HiSeq2000 platform and then de novo
      assembled using Trinity software. A total of 59 SVMP contigs were annotated
      through a Blastn search against the serpent nucleotide database from NCBI. Among
      them, disintegrins were the most abundant transcripts (75%) followed by the P-III
      class SVMPs (25%). The P-II SVMPs were scarce (0.002%), while no P-I SVMPs were
      detectable in the transcriptome. For detailed structural analysis, contigs were
      conceptually translated and compared with amino acid sequences from other RVs and
      other vipers using Clustal Omega. The RTS-disintegrin (jerdostatin homolog) was
      the most abundant among transcripts corresponding to 5 disintegrin isoforms. From
      10 isoforms of SVMPs, RVV-X, and Vipera lebetina apoptosis-inducing protease
      (VLAIP) homolog, hereby termed Daboia siamensis AIP (DSAIP), were found to be
      highly expressed. Venom protein analysis using SDS-PAGE followed by mass
      spectrometry revealed that the disintegrin was scarce, while the latter two SVMPs
      were abundant. These two proteins can contribute to severe clinical
      manifestations caused by MRV envenomation.

PMID- 29567104
TI  - Predictors of a successful statin reattempt after an adverse reaction.
AB  - BACKGROUND: Many patients can tolerate statin therapy after an adverse reaction.
      However, optimal patient selection criteria and methods of reattempting statin
      therapy after an adverse reaction are unknown. OBJECTIVE: To identify patient and
      treatment characteristics associated with a successful statin reattempt after an
      adverse reaction. METHODS: We retrospectively studied adults treated in primary
      care practices affiliated with 2 academic medical centers between 2000 and 2012
      who reattempted statin therapy after an adverse reaction. Statin reattempts were
      considered successful if the patient had at least 2 statin prescriptions after
      discontinuation of the original statin, and had an active electronic medical
      record statin record at 2 years after the adverse reaction. RESULTS: Among 6196
      patients included in the study, 4536 (73.2%) successfully reattempted statin
      therapy. In multivariable analysis, history of coronary artery disease, stroke,
      or diabetes (odds ratio [OR] 1.195; P = .008) and reattempted treatment with a
      different statin (OR 1.463; P < .0001) were associated with greater odds of a
      successful reattempt. Adverse reaction during the first year after statin
      initiation (OR 0.721; P < .0001) or myalgia or myopathy (OR 0.807; P = .001) as
      well as history of adverse reactions to nonstatin drugs (OR 0.908; P < .0001)
      were associated with lower odds. CONCLUSIONS: Nature and timing of the adverse
      reaction, patient's medical history and the medication prescribed affected the
      likelihood of a successful reattempt of statin therapy after an adverse reaction.
      These findings suggest that a patient-centered approach to restarting statins
      should be considered for patients at high cardiovascular risk to improve the
      chances of success.

PMID- 29567105
TI  - Proximal and distal alignment of normal canine femurs: A morphometric analysis.
AB  - Many researchers are interested in femoral conformation because most orthopaedic
      problems of the long bones occur in the femur and its joints. The neck-shaft
      (NSA) and the anteversion (AVA) angles are good predictors for understanding the
      orientation of the proximal end of the femur. The varus (aLDFA) and procurvatum
      (CDFA) angles have also been used to understand the orientation of the distal end
      of the femur. The purposes of this study were to investigate the relationship
      between the proximal and distal angles of the femur and to compare the distal
      femoral angles in male and female dogs in order to investigate the sexual
      dimorphism. The measurements of normal CDFAs, which have not been previously
      reported, may also provide a database of canine distal femoral morphology. A
      total of 75 cleaned healthy femora from different breeds or mixed breed of dogs
      were used. The three-dimensional images were reconstructed from computed
      tomographic images. The AVA, NSA, aLDFA and CDFA were measured on the 3D images.
      The correlation coefficients were calculated among the measured angles. The
      distal femoral angles were also compared between male and female femora. The 95%
      confidence intervals of the AVA and the NSA were calculated to be 24.22 degrees 
      29.50 degrees  and 144.97 degrees -147.50 degrees , respectively. The 95%
      confidence intervals of the aLDFA and the CDFA for all studied dogs were 92.62
      degrees -94.08 degrees  and 89.09 degrees -91.94 degrees , respectively. The NSA
      showed no correlation with either the aLDFA or CDFA. There was a weak inverse
      correlation between the AVA and CDFA and a weak positive correlation between the
      AVA and aLDFA. The differences in the aLDFA and CDFA measurements between male
      and female dog were not significant. In conclusion, femoral version, regardless
      of the plane, might have little influence on distal femoral morphology in normal
      dogs. Besides this, there is no evidence of a sexual dimorphism in the varus and
      procurvatum angles of the dog distal femur. The data from this study may be used
      in both orthopaedic studies and for clinical applications related to the distal
      femur of dogs.

PMID- 29567106
TI  - Scalable and cleavable polysaccharide nanocarriers for the delivery of
      chemotherapy drugs.
AB  - : While polysaccharide-based nanocarriers have been recognized for their crucial
      roles in tumor theranostics, the industrial-scale production of nanotherapeutics
      still remains a significant challenge. Most current approaches adopt a
      postpolymerization self-assembly strategy that follows a separate synthetic step
      and thus suffers from subgram scale yields and a limited range of application. In
      this study, we demonstrate the kilogram-scale formation of polysaccharide
      polyacrylate nanocarriers at concentrations of up to 5 wt% through a one-pot
      approach - starting from various acrylate monomers and polysaccharides - that
      combines aspects of hydrophobicity-induced self-assembly with the free radical
      graft copolymerization of acrylate monomers from polysaccharide backbones into a
      single process that is thus denoted as a graft copolymerization induced self
      assembly. We also demonstrate that this novel approach is applicable to a broad
      range of polysaccharides and acrylates. Notably, by choosing a crosslinker that
      bears a disulfide group and two vinyl capping groups to structurally lock the
      nanocarriers, the products are rendered cleavable in the reducing environments
      encountered at tumor sites and thus provide ideal candidates for the construction
      of anticancer nanotherapeutic systems. In vitro and in vivo studies demonstrated
      that the use of this nanocarrier for the delivery of doxorubicin hydrochloride
      (DOX) significantly decreased the side effects of DOX and improved the bio-safety
      of the chemotherapy accordingly. STATEMENT OF SIGNIFICANCE: While polysaccharide
      based nanocarriers have been recognized for their crucial roles in tumor
      theranostics, the industrial-scale production of these nanotherapeutics still
      remains a significant challenge. Most current approaches adopt a post
      polymerization self-assembly strategy which that follows a separate synthetic
      step, and thus suffers from sub-gram scale yields and a limited range of
      application. In this study, the hydrophobic effect was combined with free radical
      polymerization to facilitate the graft copolymerization-induced self-assembly
      (GISA) of acrylate monomers with various hydrophobicities to construct cleavable
      polysaccharide-polyacrylate nanocarriers at a high efficiency with excellent
      potential for industrial-scale production. We envision that these nanocarriers
      will contribute to the development of tumor nanotheranostics that combine the
      biological functionalities of polysaccharides with the unmatched application
      specific flexibility of nanocarriers.

PMID- 29567107
TI  - The role of the temporoparietal junction in implicit and explicit sense of
      agency.
AB  - The experience of being in control of one's actions and thier outcomes is called
      the sense of agency. This is a fundamental feature of our human experience, and
      may underpin important social functions such as morality and responsibility.
      Sense of agency can be measured explicitly, by asking people to report their
      experience, or implicitly by recording the perceived time interval between
      actions and outcomes (intentional binding). The current studies used transcranial
      direct current stimulation to assess the role of left and right temporoparietal
      junction in both implicit and explicit sense of agency. Participants were
      informed that they could control the volume output of the computer with one of
      two buttons. Participants experienced reduced sense of agency when the outcome
      was inconsistent with their action. However, binding did not differ between
      congruent and incongruent action-outcomes. The modulation of explicit agency
      ratings by action-outcome congruency was significantly reduced by right TPJ
      stimulation (experiment 1) but not left TPJ stimulation (experiment 2). Implicit
      agency was not affected in either stimulation condition. These findings are
      discussed in terms of the possible neural mechanisms of implicit and explicit
      sense of agency.

PMID- 29567108
TI  - Alternative outcomes create biased expectations regarding the received outcome:
      Evidence from event-related potentials.
AB  - After choosing between uncertain options, one might get feedback on both the
      outcome of the chosen option and the outcome of the unchosen option (the
      alternative). Behavioral research has shown that in such cases people engage in
      outcome comparison, and that the alternative outcome influences the way one
      evaluates his own received outcome. Moreover, this influence differs whether one
      was responsible or not for the choice made. In two studies, we looked for the
      electrophysiological correlates of outcome comparison. Subjects chose one of two
      boxes shown on the screen, each box contained a gain or a loss. The alternative
      outcome was always revealed first, followed by the received outcome. In half of
      the trials the software picked one box instead of subjects. We tested whether the
      feedback-related negativity (FRN) and the P3 elicited by the received reflect
      outcome comparison. As expected, we found that the FRN and P3 were more positive
      when the received outcome was a gain (vs. a loss). The FRN and P3 were also
      sensitive to the value of the alternative outcome, but contrary to our
      predictions, they were more positive when the alternative outcome was a gain (vs.
      a loss). As the FRN and P3 are sensitive to expectations, we hypothesized that
      our findings might result from subjects' biased expectations: subjects might have
      wrongly believed that a good (bad) alternative outcome signaled a bad (good)
      received outcome. This hypothesis, coined as the Alternative Omen Effect, was
      confirmed in parallel in a series of behavioral experiments: people see an
      illusory negative correlation between the uncorrelated outcomes of choice options
      (reported in Marciano-Romm et al. (2016)). A challenge for future research will
      be to disentangle the effects of expectation from those of outcome comparison.

PMID- 29567109
TI  - Diaphragmatic shear modulus at various submaximal inspiratory mouth pressure
      levels.
AB  - This study assessed the shear modulus of the diaphragm at various submaximal
      inspiratory mouth pressure levels by ultrasound shear wave elastography. In 14
      healthy male subjects, diaphragmatic shear moduli were assessed at end expiration
      during resting breathing and at submaximal inspiratory tasks at 15, 30, 45, 60,
      and 75% of the maximal inspiratory mouth pressure. The shear modulus increased
      along with mouth pressure, and the mouth-pressure-shear-modulus relationship fit
      the second-order polynomial regression equation (r2 = 0.99 +/- 0.01; all
      subjects, r2 >= 0.95) better than it did the simple linear regression equation
      (r2 = 0.94 +/- 0.05; 8/14 subjects, r2 >= 0.95). The second regression
      coefficient in the second-order polynomial equation was a negative value in 10 of
      14 subjects, which indicates that the second-order polynomial regression equation
      opened downwards. These findings suggest that the diaphragmatic shear modulus
      increases along with inspiratory mouth pressure, but the rate of increase slows
      when the pressure reaches higher levels.

PMID- 29567110
TI  - ROS generation and MAPKs activation contribute to the Ni-induced testosterone
      synthesis disturbance in rat Leydig cells.
AB  - Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the
      mechanisms remain unclear. The aim of this study was to investigate the role of
      reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni
      induced disturbance of testosterone synthesis in rat Leydig cells. The
      testosterone production and ROS levels were detected in Leydig cells. The mRNA
      and protein levels of testosterone synthetase, including StAR, CYP11A1, 3beta
      HSD, CYP17A1 and 17beta-HSD, were determined. Effects of Ni on the ERK1/2, p38
      and JNK MAPKs were also investigated. The results showed that Ni triggered ROS
      generation, consequently resulted in the decrease of testosterone synthetase
      expression and testosterone production in Leydig cells, which were then
      attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1
      piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced
      testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and
      JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels
      and testosterone secretion were all alleviated by co-treatment with MAPK specific
      inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited
      testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in
      Leydig cells. In conclusion, these findings suggest that Ni causes testosterone
      synthesis disorder, partly, via ROS and MAPK signal pathways.

PMID- 29567111
TI  - Direct evidence of impaired neuronal Na/K-ATPase pump function in alternating
      hemiplegia of childhood.
AB  - Mutations in ATP1A3 encoding the catalytic subunit of the Na/K-ATPase expressed
      in mammalian neurons cause alternating hemiplegia of childhood (AHC) as well as
      an expanding spectrum of other neurodevelopmental syndromes and neurological
      phenotypes. Most AHC cases are explained by de novo heterozygous ATP1A3
      mutations, but the fundamental molecular and cellular consequences of these
      mutations in human neurons are not known. In this study, we investigated the
      electrophysiological properties of neurons generated from AHC patient-specific
      induced pluripotent stem cells (iPSCs) to ascertain functional disturbances
      underlying this neurological disease. Fibroblasts derived from two subjects with
      AHC, a male and a female, both heterozygous for the common ATP1A3 mutation G947R,
      were reprogrammed to iPSCs. Neuronal differentiation of iPSCs was initiated by
      neurogenin-2 (NGN2) induction followed by co-culture with mouse glial cells to
      promote maturation of cortical excitatory neurons. Whole-cell current clamp
      recording demonstrated that, compared with control iPSC-derived neurons, neurons
      differentiated from AHC iPSCs exhibited a significantly lower level of ouabain
      sensitive outward current ('pump current'). This finding correlated with
      significantly depolarized potassium equilibrium potential and depolarized resting
      membrane potential in AHC neurons compared with control neurons. In this cellular
      model, we also observed a lower evoked action potential firing frequency when
      neurons were held at their resting potential. However, evoked action potential
      firing frequencies were not different between AHC and control neurons when the
      membrane potential was clamped to -80 mV. Impaired neuronal excitability could be
      explained by lower voltage-gated sodium channel availability at the depolarized
      membrane potential observed in AHC neurons. Our findings provide direct evidence
      of impaired neuronal Na/K-ATPase ion transport activity in human AHC neurons and
      demonstrate the potential impact of this genetic defect on cellular excitability.

PMID- 29567112
TI  - Reference intervals for measured and calculated free 25-hydroxyvitamin D in
      normal pregnancy.
AB  - The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the
      analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status
      during pregnancy, since vitamin D-binding protein (DBP) concentrations increase
      throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP
      thus strongly influencing total 25(OH)D. The concentration of the biologically
      active free 25(OH)D - on the other hand - is much less dependent on the DBP
      concentrations. The study was conducted in May-June 2016 in 368 Caucasian
      pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was
      either measured directly by commercial ELISA kit or assessed by calculation via
      total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection
      method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester
      (by 12% and 21%, p < 0.05 and p < 0.001, for measured and calculated free
      25(OH)D, respectively), whereas total 25(OH)D was not decreased in late
      pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with
      serum calcium (p = 0.251), whereas free 25(OH)D was significantly (p = 0.007 for
      measured free 25(OH)D and p < 0.001 for calculated free 25(OH)D) positively
      correlated with calcium. All 25(OH)D isoforms were significantly negatively
      correlated with bone-specific alkaline phosphatase (BSAP), however the
      correlation strength was the lowest with total 25(OH)D (rho = -0.108, p = 0.038),
      whereas both measured and calculated free 25(OH)D revealed better associations
      with BSAP (rho = -0.203 and rho = -0.211 for measured and calculated free
      25(OH)D, respectively, p < 0.001 for both). We established pregnancy trimester
      specific reference intervals for free measured and calculated 25(OH)D and DBP.
      Both measured and calculated free 25(OH)D showed better correlations with
      parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of
      measuring free 25(OH)D in pregnant women are suitable as novel laboratory
      parameter for vitamin D status monitoring during human pregnancy and might
      replace in the future the routine total 25(OH)D assessment.

PMID- 29567113
TI  - Perception of the quality of care, work environment and sleep characteristics of
      nurses working in the National Health System.
AB  - OBJECTIVE: To describe nurses' perception in relation to the quality of care and
      their work environment, as well as to describe their quality of sleep. To analyze
      the relationship between ward and work shift with nurses' perception of their
      work environment, sleep quality and day time drowsiness. METHODS: A multicentre,
      observational and descriptive study carried out between 2012-2014 in seven
      hospitals of the Spanish National Health System. Work environment, work
      satisfaction, sleep quality and quality of patient care were evaluated through
      validated tools. RESULTS: 635 registered nurses participated in the study. Eighty
      three point seven percent perceived the quality of cares as good/excellent, and
      55.1% rated the work environment of their hospital as good/excellent. PES-NWI
      classified 39% of hospitals as unfavourable and 20% as favourable. Fifteen point
      four percent of the nurses had a high level of burnout and 58.3% had low burnout.
      Sleep quality was 6.38 for nurses working on day shifts, 6.78 for the rotational
      shifts and 7.93 for night shifts. Significant differences were found between
      subjective sleep quality score, sleep duration, sleep disturbances and daytime
      dysfunction. CONCLUSIONS: In the provision of quality care services, there is a
      multitude of related factors such as shift, ward, satisfaction, and nurses'
      perceptions of patient safety and sleep quality.

PMID- 29567114
TI  - Human skin barrier formation takes place via a cubic to lamellar lipid phase
      transition as analyzed by cryo-electron microscopy and EM-simulation.
AB  - The skin's permeability barrier consists of stacked lipid sheets of splayed
      ceramides, cholesterol and free fatty acids, positioned intercellularly in the
      stratum corneum. We report here on the early stage of skin barrier formation
      taking place inside the tubuloreticular system in the secretory cells of the
      topmost viable epidermis and in the intercellular space between viable epidermis
      and stratum corneum. The barrier formation process was analysed in situ in its
      near-native state, using cryo-EM combined with molecular dynamics modeling and EM
      simulation. Stacks of lamellae appear towards the periphery of the
      tubuloreticular system and they are closely associated with granular regions.
      Only models based on a bicontinuous cubic phase organization proved compatible
      with the granular cryo-EM patterns. Only models based on a dehydrated lamellar
      phase organization agreed with the lamellar cryo-EM patterns. The data support
      that human skin barrier formation takes place via a cubic to lamellar lipid phase
      transition.

PMID- 29567115
TI  - Systems biology approach to study the role of miRNA in promoter targeting during
      megakaryopoiesis.
AB  - The distinct process of megakaryopoiesis requires occurrence of endomitosis for
      polyploidization of the megakaryocytes. Although, Cyclins, CDKs and have been
      described to regulate endomitosis, the exact mechanism still remains an enigma.
      miRNA which were otherwise known as post transcriptional gene silencers are now
      emerging with various non-canonical functions including gene regulation at pre
      transcriptional level by miRNA binding at promoter region. Out of the many
      processes they regulate, miRNA have been manifested to play a role in
      megakaryocyte differentiation. In this study an attempt has been made to identify
      miRNA that could regulate cell cycle genes (Cyclins and CDKs) by targeting their
      promoters, during megakaryopoiesis. A new computational algorithm was implemented
      using Perl programming to identify putative targets of miRNA in CDK and Cyclin
      promoters. Perl script was also used to check nuclear localizing miRNA based on
      the presence of a consensus sequence. Real-time PCR was performed to analyze the
      expression of miRNA and their predicted targets in Dami vs. PMA treated Dami
      cells. Putative targets of miRNAs with longest, high complementarity matches in
      CDK/Cyclin promoters were obtained. We identified two significant miRNA, miR
      1273g-3p and miR-619-5p with longest seed sequence matches. We further identified
      three main targets (CDK10, CDK11, Cyclin F) through which these two miRNA could
      regulate cell cycle during megakaryopoiesis. Our results reinforce the role of
      promoting targeting miRNA in regulation of cell cycle through certain CDK/Cyclins
      to support the process of endomitosis during megakaryopoiesis.

PMID- 29567116
TI  - Cardiovascular safety profile of a fixed-dose combination of glycopyrrolate and
      formoterol fumarate delivered via metered dose inhaler using co-suspension
      delivery technology.
AB  - BACKGROUND: Glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI)
      is a fixed-dose combination of the long-acting muscarinic antagonist (LAMA),
      glycopyrrolate (GP), and the long-acting beta2-agonist (LABA), formoterol
      fumarate (FF), delivered via metered dose inhaler using innovative co-suspension
      delivery technology. Here we report the results of two studies that examined the
      cardiovascular safety of GFF MDI. METHODS: The thorough QT (TQT) study was a
      Phase I, randomized, double-blind, single-dose, crossover study to assess GFF MDI
      18/9.6 (Bevespi Aerosphere(r)), GFF MDI 144/38.4 and GP MDI 144 MUg, compared
      with placebo MDI and open-label moxifloxacin 400 mg (active control) in healthy
      volunteers (PT003009). The cardiovascular safety study in patients with chronic
      obstructive pulmonary disease (COPD) was a Phase IIb, randomized, multicenter,
      double-blind, 14-day dosing, parallel-group study to evaluate GFF MDI 36/9.6, GP
      MDI 36 and FF MDI 9.6 MUg compared with open-label FF dry powder inhaler (DPI;
      Foradil(r) Aerolizer(r)) 12 MUg, in patients with moderate-to-severe COPD
      (PT003003 [NCT01349803]). RESULTS: Seventy healthy volunteers were randomized in
      the TQT study. GFF MDI 144/38.4, GFF MDI 18/9.6 and GP MDI 144 MUg all met the
      confidence interval-based criteria for negative QT prolongation potential. In the
      study in patients with COPD, 237 subjects were randomized and treated. GFF MDI
      36/9.6, GP MDI 36, and FF MDI 9.6 MUg did not result in clinically meaningful
      changes from baseline in 24-h mean heart rate at Day 14 (primary endpoint) or in
      any of the other Holter monitoring endpoints at Day 14, compared with FF DPI 12
      MUg. CONCLUSIONS: No clinically significant effects on cardiovascular safety
      occurred at therapeutic or supratherapeutic doses of GFF MDI, apart from a small
      and transient increase in heart rate following supratherapeutic dose of GFF MDI
      144/38.4 MUg. Furthermore, there were no unexpected safety findings reported in
      either healthy volunteers or patients with COPD.

PMID- 29567117
TI  - Response to Ayubi and Safiri: "Geographic Variation in Morbidity and Mortality of
      Cerebrovascular Diseases in Korea during 2011-2015: Bias Due to Spatial
      Autocorrelation and Modifiable Areal Unit Problem".

PMID- 29567118
TI  - Cortical Hand Knob Stroke: Report of 25 Cases.
AB  - BACKGROUND: Although uncommon, cortical hand knob territory stroke is a well
      defined stroke entity that mimics peripheral nerve damage. Atherosclerosis and
      hypertension are the most prevalent risk factors for the disease. Embolic origin,
      either artery-to-artery or cardioembolic, has been suggested as the most probable
      underlying mechanism. MATERIALS AND METHODS: Twenty-five patients with isolated
      hand palsy due to central origin were admitted to our department between 2006 and
      2016. Cortical lesions were proven by either computed tomography or magnetic
      resonance imaging. RESULTS: The average age was 67 +/- 12 years. Most of the
      cases were first-ever strokes (n = 23, 92%). Isolated infarct in the hand knob
      region was found in 18 of the 25 cases, whereas 7 had multiple acute infarctions.
      Supra-aortic atherosclerosis was found in 21 patients, 8 of them had 50% or
      greater ipsilateral stenosis of the internal carotid artery. Hypertension was the
      second most prevalent risk factor (n = 20, 80%). Quick improvement of symptoms
      was seen in almost every case (mean follow-up 17.5 months), 9 patients showed
      complete recovery, whereas 2 remained disabled and 1 died due to a malignant
      disease. Three patients suffered a recurrent stroke on follow-up. CONCLUSIONS: We
      conclude that distal arm paresis is a rare presentation of acute stroke with
      usually benign course.

PMID- 29567120
TI  - Response to Commentary on "Short-Term Outcome of Spontaneous Intracerebral
      Hemorrhage in Algarve, Portugal: Retrospective Hospital-Based Study".

PMID- 29567119
TI  - Clinical Features, Surgical Treatment, and Long-Term Outcome in Children with
      Hemorrhagic Moyamoya Disease.
AB  - BACKGROUND: The objective of this study was to elucidate the clinical features,
      surgical treatment, and long-term outcome in pediatric patients with moyamoya
      disease (MMD). METHODS: We retrospectively reviewed 46 pediatric patients with
      hemorrhagic MMD at Beijing Tiantan Hospital. Clinical features, radiological
      findings, and outcomes were analyzed. RESULTS: The mean age at diagnosis was 13.6
      +/- 3.6 years. The ratio of girls to boys was 1.0:1.1. Familial occurrence was
      4.3%. The primary symptoms at initial presentation were intraventricular
      hemorrhage (IVH) (47.8%), intracerebral hemorrhage (ICH) (37.0%), ICH with IVH
      (13.0%), and subarachnoid hemorrhage (2.2%). Most patients presented with Suzuki
      stage 3 or 4 MMD. Posterior cerebral artery involvement was observed in 22
      (18.4%) patients. During the average follow-up of 126.1 +/- 96.0 months, 11 of 53
      (20.8%) conservatively treated hemispheres and 1 of 36 (2.8%) surgically treated
      hemispheres experienced a stroke event (P < .05). There was a difference in the
      Kaplan-Meier curve of stroke between the 2 groups (log rank test, P < .05). What
      is more, the rate of perfusion improvement in surgically treated patients was
      higher than in those conservatively treated patients 3 months after discharge (P
      < .05). CONCLUSIONS: Revascularization surgery has a role in the prevention of
      recurrent strokes and can improve cerebral perfusion in pediatric patients with
      hemorrhagic MMD. Further study is needed to determine which bypass surgery is
      more beneficial for pediatric patients with hemorrhagic MMD.

PMID- 29567121
TI  - Parent Involvement in the Pediatric Resident Applicant Interview.
AB  - BACKGROUND: Parents and patients are actively involved in the clinical learning
      environment, yet scant literature exists about their involvement in the residency
      interview process. We aimed to pilot a process of including parents in resident
      interviews and to determine its value. METHODS: During the 2016-17 residency
      interview cycle, 22 parent volunteers, blinded to applicant credentials,
      conducted brief structured interviews with 118 applicants. We then surveyed all
      parents and applicants with the use of mixed methods: descriptive statistics to
      analyze 5-point Likert-type-scale responses, and content analysis to identify
      themes from open-ended questions. Although parent interviews were not used in
      ranking, we later compared final composite parent interview scores (1-10, with 10
      being high) among the final rank and match list candidates. RESULTS: Response
      rates were high for both groups (parents 100%; resident applicants 98.3%).
      Parents felt strongly positive about meeting applicants (mean +/- SD, 5.00 +/-
      0.00), the value of parent participation (4.90 +/- 0.30), and their own
      experience (4.95 +/- 0.22). Applicants felt positive about meeting parents (4.45
      +/- 0.70), the value of parent participation (3.92 +/- 0.84), and their own
      experience (4.51 +/- 0.67). Several themes emerged from both groups, with the
      most salient parent themes including the value of patient-centered perspectives
      and appreciation and joy of meeting applicants. Parent interview scores
      correlated with the final match list, with matched applicants scoring higher
      (9.08 vs 8.51; P = .05). CONCLUSIONS: Involvement of parents in the pediatric
      residency interview process is achievable, is perceived positively by parents and
      applicants, and may provide valuable perspectives for consideration in residency
      selection.

PMID- 29567122
TI  - Can three-dimensional pelvimetry using low-dose stereoradiography replace low
      dose CT pelvimetry?
AB  - PURPOSE: To evaluate the reliability of pelvimetric measurements performed using
      stereoradiographic imaging (SRI), and to assess maternal and fetal radiation
      doses compared to low-dose computer tomography (CT) pelvimetry. MATERIALS AND
      METHODS: Thirty-five pregnant women (mean age, 29.6+/-5.5 [SD] years; range: 20
      41 years) were prospectively included. All women underwent simultaneous frontal
      and lateral low-dose SRI and low-dose CT examination of the pelvis. Pelvimetry
      measurements were obtained from both examinations and radiation doses obtained
      with the two techniques were compared. RESULTS: SRI-CT correlation (Pearson
      coefficient correlation [r]; mean bias [mb]) was strong for transverse inlet
      diameter (r=0.92; mb=-0.09cm), anteroposterior diameter of the pelvic inlet
      (r=0.92; mb = 0.47cm), maximal transverse diameter (r=0.9; mb=0.21cm), sacrum
      length (r=0.9; mb=0.09cm). Correlation was good. Correlation was good for the
      sacrum depth (r=0.75; mb=0.06cm) and Magnin's index (r=0.7; mb=0.5cm).
      Correlation was moderate for anteroposterior diameter of pelvic outlet (r=0.6;
      mb=0.52cm). The fetal dose was 13.1 times lower using SRI (87+/-26MUGy) than CT
      (1140+/-220MUGy, P<0.0001). The effective maternal dose was 3.1 times lower using
      SRI (97+/-21MUSv) than CT (310+/-60MUSv; P<0.0001). CONCLUSION: Pelvic inlet
      measurements using SRI are reliable. Compared to CT pelvimetry, SRI leads to a
      significant decrease in fetal and maternal radiation doses. These findings should
      prompt physicians to use SRI as the first-line approach for pelvimetry.

PMID- 29567124
TI  - Endoplasmic reticulum stress in pulmonary fibrosis.
AB  - Endoplasmic reticulum (ER) stress is associated with development and progression
      of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). ER stress
      was first implicated in the pathogenesis of IPF >15 years ago with the discovery
      of disease-causing mutations in surfactant protein C, which result in a misfolded
      gene product in type II alveolar epithelial cells (AECs). ER stress and the
      unfolded protein response (UPR) have been linked to lung fibrosis through
      regulation of AEC apoptosis, epithelial-mesenchymal transition, myofibroblast
      differentiation, and M2 macrophage polarization. Although progress has been made
      in understanding the causes and consequences of ER stress in IPF and a number of
      chronic fibrotic disorders, further studies are needed to identify key factors
      that induce ER stress in important cell types and define critical down-stream
      processes and effector molecules that mediate ER stress-related phenotypes. This
      review discusses potential causes of ER stress induction in the lungs and current
      evidence linking ER stress to fibrosis in the context of individual cell types:
      AECs, fibroblasts, and macrophages. As our understanding of the relationship
      between ER stress and lung fibrosis continues to evolve, future studies will
      examine new strategies to modulate UPR pathways for therapeutic benefit.

PMID- 29567125
TI  - Point-of-care testing for CXCL13 in Lyme neuroborreliosis.
AB  - Cerebrospinal fluid chemokine (C-X-C motif) ligand 13 (CXCL13) is a marker for
      Lyme neuroborreliosis (LNB). CXCL13 lateral flow immunoassay (LFA) was compared
      with CXCL13 ELISA. CXCL13 LFA results correlated strongly with CXCL13 ELISA
      results. CXCL13 LFA is a rapid and easy-to-perform test, which is suitable for
      routine point-of-care diagnostics of suspected LNB patients.

PMID- 29567123
TI  - Fibrosis: Lessons from OMICS analyses of the human lung.
AB  - In recent decades there has been a significant shift in our understanding of
      idiopathic pulmonary fibrosis (IPF), a progressive and lethal disorder. While
      initially much of the mechanistic understanding was derived from hypotheses
      generated from animal models of disease, in recent decades new insights derived
      from humans with IPF have taken precedence. This is mainly because of the
      establishment of large collections of IPF lung tissues and patient cohorts, and
      the emergence of high throughput profiling technologies collectively termed
      'omics' technologies based on their shared suffix. In this review we describe
      impacts of 'omics' analyses of human IPF samples on our understanding of the
      disease. In particular, we discuss the results of genomics and transcriptomics
      studies, as well as proteomics, epigenomics and metabolomics. We then describe
      how these findings can be integrated in a modified paradigm of human idiopathic
      pulmonary fibrosis, that introduces the 'hallmarks of aging' as a central theme
      in the IPF lung. This allows resolution of all the disparate cellular and
      molecular features in IPF, from the central role of epithelial cells, through the
      dramatic phenotypic alterations observed in fibroblasts and the numerous
      aberrations that inflammatory cells exhibit. We end with reiterating a call for
      renewed efforts to collect and analyze carefully characterized human tissues, in
      ways that would facilitate implementation of novel technologies for high
      resolution single cell omics profiling.

PMID- 29567126
TI  - Distribution of streptococcal groups causing infective endocarditis: a
      descriptive study.
AB  - The purpose of this study was to describe the distribution of streptococci
      causing infective endocarditis (IE). A total of 296 patients with definite IE
      admitted from July 2007 to December 2014 were identified, with microbial
      identification done by a combination of blood culture, valve culture, and valve
      polymerase chain reaction (PCR). The overall distribution of streptococci was 76%
      viridans (n = 224), 17% pyogenic (50), 6% nutritionally variant (17), and 2%
      anaerobic (5). Sixty-three (21%) viridans group streptococci were not identified
      further. The distribution of the remaining 161 viridans group streptococci was
      Streptococcus mitis group 61%, S. bovis group 15%, S. mutans group 13%, S.
      anginosus group 9%, and S. salivarius group 1%. Of the 50 pyogenic streptococci,
      78% were S. agalactiae and 16% were S. dysgalactiae. PCR was significantly more
      sensitive than culture in identifying streptococci in excised heart valves.

PMID- 29567127
TI  - Poor yield of Clostridium difficile testing algorithms using glutamate
      dehydrogenase antigen and C. difficile toxin enzyme immunoassays in a pediatric
      population with declining prevalence of clostridium difficile strain BI/NAP1/027.
AB  - We compared the performance of algorithmic Clostridium difficile infection (CDI)
      diagnosis with four molecular tests in children. Stool samples in patients 1-18
      years old were tested with an algorithm (C. Diff Quik Chek Complete (QCC)
      reflexed to illumigene C. difficile); AmpliVue C. difficile (ACD); Lyra Direct C.
      difficile (Lyra); BD MAX C diff (BDM); and Xpert C. difficile (XCD). The gold
      standard was positivity by two tests. Sensitivity, specificity, positive
      predictive value, and negative predictive value were 85%, 99%, 93%, 97% for the
      algorithm; 21%, 99%, 78%, 87% for QCC's toxin component; 94%, 99%, 94%, 99% for
      ACD; 88%, 99%, 94%, 98% for Lyra; 94%, 100%, 100%, 99% for BDM, and 94%, 99%, 94%
      and 99% for XCD. 9.6% of samples were ribotype 027. Algorithms may detect CDI
      with lower sensitivity compared to molecular methods in children. This may be
      related to low prevalence of NAP-1/ribotype 027.

PMID- 29567128
TI  - Oritavancin in vitro activity against gram-positive organisms from European and
      United States medical centers: results from the SENTRY Antimicrobial Surveillance
      Program for 2010-2014.
AB  - The in vitro activity of oritavancin was assessed against 44,715 gram-positive
      pathogens causing infections in European and United States (US) hospitals (2010
      2014). There were no substantive differences (>+/-2-fold dilution) in oritavancin
      MIC50 or MIC90 values for different species/organism groups over time or by
      region. Oritavancin (99.9% susceptible) showed modal MIC, MIC50, and MIC90
      results of 0.03, 0.03, and 0.06-0.12 mg/L when tested against Staphylococcus
      aureus, regardless of methicillin susceptibility, year, or region. Coagulase
      negative staphylococci from the US and Europe demonstrated equal MIC50 values for
      oritavancin (MIC50, 0.03 mg/L). Oritavancin inhibited 99.9% of Enterococcus
      faecalis and all E. faecium at <=0.5 mg/L, including vancomycin-resistant
      isolates. Oritavancin exhibited MIC50 results of 0.03 and <=0.008 mg/L when
      tested against beta-hemolytic and viridans group streptococci isolates,
      respectively, regardless of geographical region. Oritavancin maintained potent
      activity in vitro against this contemporary collection of European and US gram
      positive isolates over 5 years (2010-2014).

PMID- 29567129
TI  - [Statement by the Spanish Paediatric Association in relation to gender diversity
      in childhood and adolescence: Ethical and legal view from a multidisciplinary
      perspective].
AB  - An ethical and legal view of gender diversity in childhood and adolescence is
      presented from the perspective of the best interest of the child and the
      principle of protection against vulnerability. The identification of gender
      diversity in childhood and adolescence is a process that requires support,
      coordination and a multidisciplinary team that improves care and helps to obtain
      evidence that is lacking today. Secure, equitable and comprehensive access to
      care and health care should be guaranteed when required. It is necessary to
      promote a changing of social outlook, capable of overcoming the stereotypes that
      lead to discrimination and increase suffering. Respect for gender diversity in
      childhood and adolescence is a fundamental Human Right. The recognition of a
      positive value in diversity is an ethical imperative. All of this, without
      forgetting that we are talking about minors often in contexts of vulnerability,
      and currently very uncertain, so prudence is the main rule that should guide
      decision-making.

PMID- 29567130
TI  - Perioperative management of patients with coronary artery disease undergoing non
      cardiac surgery: Summary from the French Society of Anaesthesia and Intensive
      Care Medicine 2017 convention.
AB  - This review summarises the specific stakes of preoperative, intraoperative, and
      postoperative periods of patients with coronary artery disease undergoing non
      cardiac surgery. All practitioners involved in the perioperative management of
      such high cardiac risk patients should be aware of the modern concepts expected
      to decrease major adverse cardiac events and improve short- and long-term
      outcomes. A multidisciplinary approach via a functional heart team including
      anaesthesiologists, cardiologists and surgeons must be encouraged. Rational and
      algorithm-guided management of those patients should be known and implemented
      from preoperative to postoperative period.

PMID- 29567131
TI  - Midterm outcomes after aortic valve neocuspidization with glutaraldehyde-treated
      autologous pericardium.
AB  - OBJECTIVE: We had previously reported the short-term results of the aortic valve
      neocuspidization (AVNeo) procedure. We have now evaluated the midterm results
      with the longest follow-up of 118 months. METHODS: From April 2007 through
      December 2015, 850 patients were treated with AVNeo using autologous pericardium.
      Medical records of these patients were retrospectively reviewed. The procedure
      was on the basis of independent tricuspid replacement using autologous
      pericardium. The distances between the commissures were measured with an original
      sizing device, the pericardial cusp was trimmed using an original template, and
      then sutured to the annulus. RESULTS: There were 534 patients with aortic
      stenosis, 254 with aortic regurgitation, 61 with aortic stenoregurgitation, 19
      with infective endocarditis, and 5 with a previous aortic valve procedure.
      Besides 596 patients with tricuspid aortic valve, 224 patients had bicuspid
      valve, 28 had unicuspid valve, and 2 had quadricuspid valve. There were 444 male
      and 406 female patients. The median age was 71 (range, 13-90) years old.
      Preoperative echocardiography revealed a peak pressure gradient average of 68.9
      +/- 36.3 mm Hg with aortic stenosis. Surgical annular diameter was 20.9 +/- 3.3
      mm. There was no conversion to a prosthetic valve replacement. There were 16 in
      hospital mortalities. Postoperative echocardiography revealed a peak pressure
      gradient average of 19.5 +/- 10.3 mm Hg 1 week after surgery and 15.2 +/- 6.3 mm
      Hg 8 years after surgery. Fifteen patients needed reoperation (13 infective
      endocarditis, 1 break of thread, and 1 tear of cusp case). The mean follow-up
      period was 53.7 +/- 28.2 months. Actuarial freedom from death, cumulative
      incidence of reoperation, and that of recurrent moderate aortic regurgitation or
      greater was 85.9%, 4.2%, and 7.3%, respectively, with the longest follow-up of
      118 months. CONCLUSIONS: The midterm outcomes of AVNeo using autologous
      pericardium were satisfactory in 850 patients with various aortic valve diseases.
      However, further randomized, multicenter prospective studies are needed to
      confirm the results of the current study.

PMID- 29567132
TI  - Discussion.

PMID- 29567133
TI  - Expression analysis of immune genes in goldfish (Carassius auratus) infected with
      the monogenean parasite Gyrodactylus kobayashii.
AB  - Heavy infection with the ectoparasite Gyrodactylus kobayashii commonly leads to
      high mortality of ornamental goldfish Carassius auratus. To understand the
      underlying mechanisms of goldfish against infection of gyrodactylids,
      transcription responses of immune-related genes including IL-1beta2, TNFalpha1,
      TNFalpha2, IFN-gamma, TGFbeta, MHC II beta, TCRbeta1 and complement factor C3
      were studied by real-time quantitative PCR analysis. Significant increases of
      expression of inflammatory genes such as IL-1beta2, TNFalpha1, TNFalpha2 and
      TGFbeta were detected at days 7 and 14 post-infection (pi). No significant
      differences of G. kobayashii load were observed in response to primary infection
      and re-infection. In addition, the transcript levels of genes involved in
      adaptive immunity such as MHC II beta and TCRbeta1 remained unchanged. Curiously,
      fish moderately infected with gyrodactylid showed elevated expression IL-1beta2,
      TNFalpha1 and TNFalpha2. In all the gyrodactylids-infected fish, expression of
      complement factor C3 was consistently inhibited. The results extend current
      knowledge to the understanding of gyrodactylid infection in fish and support the
      previous findings that innate immunity is indispensable for controlling parasite
      infection.

PMID- 29567134
TI  - A novel white spot syndrome virus-induced gene (MjVIG1) from Marsupenaeus
      japonicus hemocytes.
AB  - cDNA of a newly recognized white spot syndrome virus (WSSV)-induced gene (MjVIG1)
      was characterized from Marsupenaeus japonicus hemocytes; this gene encodes a
      protein that lack similarity to any known characterized protein. To identify this
      novel gene, we mainly conducted transcript level analysis, immunostaining and
      flow cytometry after WSSV infection. MjV1G1 transcript levels were also measured
      after Yellow head virus (YHV) and Vibrio parahaemolyticus infection tests. In non
      infected and WSSV-infected shrimp, MjVIG1 was observed in granule-containing
      hemocytes. In addition, the MjVIG1 transcript level and ratio of MjVIG1-positive
      hemocytes both significantly increased, and number of MjVIG1-positive hemocytes
      slightly increased after WSSV infection. In contrast, MjVIG1 transcript level did
      not change after YHV and V. parahaemolyticus infection. These results indicated
      that MjVIG1 might be a WSSV-specific induced gene in M. japonicus hemocytes.

PMID- 29567135
TI  - Class B CpG-ODN2006 is highly associated with IgM and antimicrobial peptide gene
      expression through TLR9 pathway in yellowtail Seriola lalandi.
AB  - The purpose of this study was to characterize the TLR9 gene from yellowtail
      (Seriola lalandi) and evaluate its functional activity using the class B Cytosine
      phosphate-guanine-oligodeoxynucleotide2006 (CpG-ODN2006) in an in vivo experiment
      after one-week immunostimulation. The gene expressions of TLR9, Immunoglobulin M
      (IgM), antimicrobial peptides and cytokines were evaluated by real time PCR, and
      humoral immune parameters were analyzed in serum. The TLR9 nucleotide sequence
      from yellowtail was obtained using the whole-genome shotgun sequencing method and
      bioinformatics tools. The yellowtail full-length cDNA sequence of SlTLR9 was 3789
      bp in length, including a 66-bp 5'-untranslated region (UTR), a 3'-UTR of 528 bp,
      and an open reading frame (ORF) of 3192 bp translatable to 1064 amino acid
      showing a high degree of similarity with the counterparts of other fish species
      and sharing common structural architecture of the TLR family, including LRR
      domains, one C-terminal LRR region, and a TIR domain. Gene expression studies
      revealed the constitutive expression of TLR9 mRNA in all analyzed tissues; the
      highest levels were observed in intestine, liver and spleen where they play an
      important role in the fish immune system. The expression levels of TLR9 after B
      class CpG-ODN2006 (the main TLR9-agonist) was significantly up-regulated in all
      analyzed tissues, with the high expression observed in spleen followed by
      intestine and skin. The CpG-B has been shown as a potent B cell mitogen, and
      interestingly, IgM mRNA transcript was up-regulated in spleen and intestine,
      which was highly correlated with TLR9 after CpG-ODN2006 stimulation. The
      antimicrobial peptides, piscidin and NK-lysine, were up-regulated in spleen and
      gill after CpG-ODN2006 injection with a high correlation (r >= 0.82) with TLR9
      gene expression. Cytokine genes were up-regulated in spleen, intestine and skin
      after CpG-ODN was compared with the control group. No significant correlation was
      observed between TLR9 and IL-1beta, TNF-alpha and Mx gene expressions. The
      results showed that CpG-ODN2006 intraperitoneal injection enhanced lysozyme,
      peroxidase and superoxide dismutase activities in serum and demonstrated that CpG
      ODN2006 can induce a specific immune response via TLR9 in which IgM and
      antimicrobial peptides must have an important role in the defense mechanisms
      against infections in yellowtail.

PMID- 29567136
TI  - Vaccination of carp against SVCV with an oral DNA vaccine or an insect cells
      based subunit vaccine.
AB  - We recently reported on a successful vaccine for carp against SVCV based on the
      intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G).
      This shows that the intramuscular (i.m.) route of vaccination is suitable to
      trigger protective responses against SVCV, and that the SVCV G-protein is a
      suitable vaccine antigen. Yet, despite the general success of DNA vaccines,
      especially against fish rhabdoviruses, their practical implementation still faces
      legislative as well as consumer's acceptance concerns. Furthermore, the i.m.
      route of plasmid administration is not easily combined with most of the current
      vaccination regimes largely based on intraperitoneal or immersion vaccination.
      For this reason, in the current study we evaluated possible alternatives to a DNA
      based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To
      this end, we tested two parallel approaches: the first based on the optimization
      of an alginate encapsulation method for oral delivery of DNA and protein
      antigens; the second based on the baculovirus recombinant expression of
      transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit
      vaccine through the oral and injection route. In addition, in the case of the
      oral DNA vaccine, we also investigated the potential benefits of the mucosal
      adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of
      various vaccine types, doses, regimes, and administration routes, no protection
      was observed, contrary to the full protection obtained with our reference i.m.
      DNA vaccine. The limited protection observed under the various conditions used in
      this study, the nature of the host, of the pathogen, the type of vaccine and
      encapsulation method, will therefore be discussed in details to provide an
      outlook for future vaccination strategies against SVCV.

PMID- 29567137
TI  - Wnt gene family members and their expression profiling in Litopenaeus vannamei.
AB  - The Wnt gene family encodes secreted glycoproteins involved in a wide variety of
      biological processes, including embryo development, cell proliferation and
      differentiation, and tissue regeneration. The Wnt pathway exists in all metazoan
      animals, however, the relevant research is rare in crustaceans. Here we described
      12 Wnt genes representing 12 Wnt gene subfamilies in the Pacific white shrimp,
      Litopenaeus vannamei. Based on homolog annotations and phylogenetic analyses, we
      named these 12 Wnt genes as LvWnt1, LvWnt2, LvWnt4-11, LvWnt16, and LvWntA. All
      the corresponding LvWnt proteins shared a conserved Wnt1 domain and 22 conserved
      cysteine residues. LvWnt1 and LvWnt6 were adjacent in a scaffold in the shrimp
      genome. Furthermore, we performed expression analyses of LvWnt genes at different
      developmental stages, during the molting process, in different tissues and after
      different pathogenic infection. We showed that each LvWnt gene had a unique
      expression pattern at different developmental stages but only a few of them
      expressed in adult shrimp. All the investigated LvWnt genes were initially
      expressed at the gastrula or limb bud embryo stages. Among them, LvWnt8 was
      specifically high expressed only in early embryos. LvWntA and LvWnt5 displayed
      high and similar expression profiles during the molting process, and LvWnt6 and
      LvWnt16 were specifically expressed in the thoracic ganglion, ventral nerve,
      intestines and gill tissues, respectively. We also found the expression of
      LvWntA, LvWnt5, LvWnt6, LvWnt9, and LvWnt16 were varied in the different tissues
      after infected with Staphylococcus aureus, Vibrio parahaemolyticus and white spot
      syndrome virus (WSSV), which indicated that they might participate in immune
      response in L. vannamei. This study provided an insight into the repertoire of
      the Wnt gene structure and expression in shrimps, and furthermore, might promote
      the understanding of development, growth and immune response of shrimps and
      crustaceans.

PMID- 29567139
TI  - Transcriptome analysis of Pacific white shrimp (Litopenaeus vannamei) challenged
      by Vibrio parahaemolyticus reveals unique immune-related genes.
AB  - Pacific white shrimp (Litopenaeus vannamei) is an important cultural species
      worldwide. However, Vibrio spp. infections have caused a great economic loss in
      Pacific white shrimp culture industry. The immune responses of Pacific white
      shrimp to the Vibrio spp. is not fully characterized. In this study, the
      transcriptomic profiles of L. vannamei hemocytes were explored by injecting with
      or without Vibrio parahaemolyticus. Totally, 42,632 high-quality unigenes were
      obtained from RNAseq data. Comparative genome analysis showed 2258 differentially
      expressed genes (DEGs) following the Vibrio challenge, including 1017 up
      regulated and 1241 down-regulated genes. Eight DEGs were randomly selected for
      further validation by quantitative real-time RT-PCR (qRT-PCR) and the results
      showed that are consistent with the RNA-seq data. Due to the lack of predictable
      adaptive immunity, shrimps rely on an innate immune system to defend themselves
      against invading microbes by recognizing and clearing them through humoral and
      cellular immune responses. Here we focused our studies on the humoral immunity,
      five genes (SR, MNK, CTL3, GILT, and ALFP) were selected from the transcriptomic
      data, which were significantly up-regulated by V. parahaemolyticus infection.
      These genes were widely expressed in six different tissues and were up-regulated
      by both Gram negative bacteria (V. parahaemolyticus) and Gram positive bacteria
      (Staphylococcus aureus). To further extend our studies, we knock-down those five
      genes by dsRNA in L. vannamei and analyzed the functions of specific genes
      against V. parahaemolyticus and S. aureus by bacterial clearance analysis. We
      found that the ability of L. vannamei was significantly reduced in bacterial
      clearance when treated with those specific dsRNA. These results indicate that
      those five genes play essential roles in antibacterial immunity and have its
      specific functions against different types of pathogens. The obtained data will
      shed a new light on the immunity of L. vannamei and pave a new way for fighting
      against the bacterial infection in Pacific white shrimp.

PMID- 29567138
TI  - Inefficient immune response is associated with microbial permissiveness in
      juvenile oysters affected by mass mortalities on field.
AB  - Since 2008, juvenile Crassostrea gigas oysters have suffered from massive
      mortalities in European farming areas. This disease of complex etiology is still
      incompletely understood. Triggered by an elevated seawater temperature, it has
      been associated to infections by a herpes virus named OsHV-1 as well as
      pathogenic vibrios of the Splendidus clade. Ruling out the complexity of the
      disease, most of our current knowledge has been acquired in controlled
      experiments. Among the many unsolved questions, it is still ignored what role
      immunity plays in the capacity oysters have to survive an infectious episode.
      Here we show that juvenile oysters susceptible to the disease mount an
      inefficient immune response associated with microbial permissiveness and death.
      We found that, in contrast to resistant adult oysters having survived an earlier
      episode of mortality, susceptible juvenile oysters never exposed to infectious
      episodes died by more than 90% in a field experiment. Susceptible oysters were
      heavily colonized by OsHV-1 herpes virus as well as bacteria including vibrios
      potentially pathogenic for oysters, which proliferated in oyster flesh and body
      fluids during the mortality event. Nonetheless, susceptible oysters were found to
      sense microbes as indicated by an overexpression of immune receptors and immune
      signaling pathways. However, they did not express important immune effectors
      involved in antimicrobial immunity and apoptosis and showed repressed expression
      of genes involved in ROS and metal homeostasis. This contrasted with resistant
      oysters, which expressed those important effectors, controlled bacterial and
      viral colonization and showed 100% survival to the mortality event. Altogether,
      our results demonstrate that the immune response mounted by susceptible oysters
      lacks some important immune functions and fails in controlling microbial
      proliferation. This study opens the way to more holistic studies on the "mass
      mortality syndrome", which are now required to decipher the sequence of events
      leading to oyster mortalities and determine the relative weight of pathogens,
      oyster genetics and oyster-associated microbiota in the disease.

PMID- 29567140
TI  - Augmentation of the antibacterial activities of Pt5-derived antimicrobial
      peptides (AMPs) by amino acid substitutions: Design of novel AMPs against MDR
      bacteria.
AB  - The ever-growing concerns on multi-drug resistant (MDR) bacteria lead to urgent
      demands for novel antibiotics including antimicrobial peptides (AMPs). Pt5, a
      peptide consisting of the C-terminal 55 residues of zebrafish phosvitin, has been
      shown to function as an antibacterial agent. Here we used Pt5 as a template to
      design new AMPs by shortening the sequence and substituting with tryptophan (W)
      and lysine (K) at selected positions. Among the resultant Pt5-derived peptides,
      Pt5-1c showed the strongest antimicrobial activity against both Gram-negative and
      Gram-positive bacteria, including MDR bacteia, with the minimum inhibitory
      concentrations (MICs) ranging from 1.2 MUM to 4.8 MUM. Electron microscopic
      examination showed that Pt5-1c was able to kill the bacteria directly. ELISA
      revealed that Pt5-1c possessed high affinity to lipopolysaccharide (LPS),
      lipoteichoic acid (LTA) and peptidoglycan (PGN). Importantly, Pt5-1c was able to
      disrupt the bacterial membrane by a combined action of membrane depolarization
      and permeabilization, with little cytotoxicity to mammalian cells. Taken
      together, these findings suggest that Pt5-1c has considerable potential for
      future development as novel peptide antibiotics against MDR bacteria.

PMID- 29567141
TI  - Intra-muscular and oral vaccination using a Koi Herpesvirus ORF25 DNA vaccine
      does not confer protection in common carp (Cyprinus carpio L.).
AB  - Koi Herpes Virus (KHV or Cyprinid Herpesvirus 3, CyHV-3) is among the most
      threatening pathogens affecting common carp production as well as the highly
      valuable ornamental koi carp. To date, no effective commercial vaccine is
      available for worldwide use. A previous study reported that three intramuscular
      injections with an ORF25-based DNA vaccine, led to the generation of neutralizing
      antibodies and conferred significant protection against an intraperitoneal
      challenge with KHV. In the present study, we set out to optimize an ORF25-based
      DNA vaccination protocol that required fewer injections and would confer
      protection upon a challenge that better resembled the natural route of infection.
      To this end, ORF25 was cloned in pcDNA3 either as a soluble protein or as a full
      length transmembrane GFP-fusion protein. We tested our ORF25-based DNA vaccines
      in multiple vaccination trials using different doses, vaccination routes (i.m.
      injection and oral gavage) and challenge methods (bath and cohabitation).
      Furthermore, we analysed local and systemic responses to the i.m. injected DNA
      vaccine through histological and RT-qPCR analysis. We observed a strong
      protection when fish received three injections of either of the two DNA vaccines.
      However, this protection was observed only after bath challenge and not after
      cohabitation challenge. Furthermore, protection was insufficient when fish
      received one injection only, or received the plasmid orally. The importance of
      choosing a challenge model that best reflects the natural route of infection and
      the possibility to include additional antigens in future DNA vaccination
      strategies against KHV will be discussed.

PMID- 29567142
TI  - Molecular characterization and function analysis of grouper (Epinephelus
      coioides) Bruton's tyrosine kinase BTK.
AB  - Bruton's tyrosine kinase (BTK) is a Tec-family tyrosine kinase and plays a
      crucial role in B cell antigen receptor (BCR) signal pathway. Mutations in humans
      and mice BTK gene results in X-linked agammaglobulinemia (XLA) and X-linked
      immunodeficiency (XLD), respectively. To study the function of BTK in teleost, we
      cloned a BTK gene from orange-spotted grouper. Homology analysis showed that the
      grouper BTK (EcBTK) had a high amino acid identity with other vertebrates (63%
      92%) and shared the highest amino acid identity with ballan wrasse Labrus
      bergylta BTK. EcBTK comprises a Bruton's tyrosine kinase pleckstrin homology (PH)
      domain, a Tec homology (TH) domain, a Src homology 3 (SH3) domain, a Src homology
      2 (SH2) domain and a Protein Kinases, catalytic (PKc) domain. Tissue distribution
      analysis showed that EcBTK was mainly expressed in immune organs. EcBTK was
      uniform distributed throughout the cytoplasm of transfected HEK293T cells and
      overexpression of EcBTK slightly down-regulates NF-kappaB activity. Ibrutinib
      treatment can reduce the phosphorylation level of grouper's BTK. In groupers
      infected with Cryptocaryon irritans, up-regulation of EcBTK were not seen in the
      early stage of infected skin and gill until days 14-21. The phosphorylation level
      of grouper BTK was significantly increased in infected skin and gill.

PMID- 29567143
TI  - Regulation of stress signaling pathways by nitro-fatty acids.
AB  - Electrophilic nitrated-fatty acids (NO2-FA, nitroalkenes) are formed during
      reactions of NO-derived oxidized species (*NO, *NO2) with either free or
      esterified polyunsaturated fatty acids. Due to their electrophilic character,
      they react with nucleophiles such as cysteine thiols in signaling proteins,
      thereby triggering downstream signaling cascades. Herein, we review two stress
      signaling pathways activated by nitroalkenes, the KEAP1-NRF2 signaling pathway
      and the heat shock response (HSR) pathway. In addition, their biological and
      pharmacological relevance are discussed. Given that perturbations in both
      proteostasis and redox balance are common in many disease processes, dual
      activation of both pathways by nitroalkenes is a promising pharmacological
      approach for their treatment.

PMID- 29567144
TI  - Molecular detection of novel circoviruses in ticks in northeastern China.
AB  - Novel circular single-stranded DNA (ssDNA) genomes have been found in various
      animals using high-throughput sequencing techniques. In this study, two circular
      ssDNA genomes were detected in adult ticks from northeastern China by Solexa
      sequencing and PCR. The two sequences shared a similar genomic organization to
      circoviruses, with genomes of 1936 bp (TiCV-1) and 1812 bp (TiCV-2), each
      including two major open read frames (ORFs), ORF1 and ORF2, encoding putative
      replicase and capsid proteins, respectively. The potential stem-loop structure of
      a circovirus was predicted in the intergenic region between the two ORFs.
      Sequence comparison showed that the genome of TiCV-2 was almost the same as that
      of TiCV-1, except for two deletions and several mutations, and they had a high
      identity of 71.3-72.9% with Raven circovirus. The infection rates of circoviruses
      were calculated by the maximum likelihood estimation as 3.2% (95% CI, 1.9-5.2%)
      for TiCV-1 in the investigated Haemaphysalis longicornis, and 1.2% (95% CI, 0.2
      4.0%) for TiCV-2 in Ixodes crenulatus from Yichun of Heilongjiang Province. These
      results indicate that the two sequences are distantly related to known circovirus
      genomes and may represent novel species in the family Circoviridae.

PMID- 29567145
TI  - Antiplasmodial activity of tick defensins in a mouse model of malaria.
AB  - Malaria is a mosquito-borne disease affecting millions of people mainly in Sub
      Saharan Africa, Asia and some South American countries. Drug resistance to first
      line antimalarial drugs (e.g. chloroquine, sulfadoxine-pyrimethamine and
      artemisinin) is a major constrain in malaria control. Antimicrobial peptides
      (AMPs) have shown promising results in controlling Plasmodium spp. parasitemia in
      in vitro and in vivo models of infection. Defensins are AMPs that act primarily
      by disrupting the integrity of cell membranes of invasive microbes. We previously
      showed that defensins from the tick Ixodes ricinus inhibited significantly the
      growth of P. falciparum in vitro, a property that was conserved during evolution.
      Here, we tested the activity of three I. ricinus defensins against P. chabaudi in
      mice. A single dose of defensin (120 MUl of 1 mg/ml solution) was administered
      intravenously to P. chabaudi-infected mice, and the parasitemia was followed for
      24 h post-treatment. Defensin treatment inhibited significantly the replication
      (measured as increases in parasitemia) of P. chabaudi after 1 h and 12 h of
      treatment. Furthermore, defensin injection was not associated with toxicity.
      These results agreed with the previous report of antiplasmodial activity of tick
      defensins against P. falciparum in vitro and justify further studies for the use
      of tick defensins to control malaria.

PMID- 29567146
TI  - A new lipid carrier protein in the cattle tick Rhipicephalus microplus.
AB  - Tick infestation in cattle reflects the main cause of economic loss to cattle
      producers. This is due to several reasons but mainly to their ability to feed on
      blood and generate a huge amount of eggs. Lipid transport in arthropods is
      achieved by highly specialized hemolymphatic lipoproteins, which resemble those
      described in vertebrate blood. Such lipoproteins continuously deliver lipids
      through the blood to growing eggs. The injection of radioactive [3H] palmitic
      acid into tick hemocoel showed that the gut, ovary, fat body and Gene's organ
      were the main organs of incorporation of this labeled fatty acid. The rate of
      [3H] palmitic acid incorporation by the organs was high up to 30 min after
      injection. The [3H] palmitic acid incorporated by these organs was later found in
      phospholipids and neutral lipids. Here, we describe the purification and
      characterization of a key player of lipid dynamics in tick hemolymph. The
      Rhipicephalus microplus lipid-apolipoprotein complex (RmLCP) is a new high
      density lipoprotein (1.18 g/mL), which accounts for over 90% of [3H] palmitic
      acid present in the hemolymph. It has a native molecular weight of 420 kDa and is
      composed of one subunit of 122 kDa. Protein identification analysis of RmLPC
      subunit showed two better hits: vitellogenin 2 (23% protein coverage) and
      vitellogenin 5 (29% protein coverage), respectively and similarities with
      hemolymphatic apolipoproteins of arachnids such as the tick Ixodes scapularis
      (80%), the mite Galendromus occidentalis (44%) and the spider Parasteatoda
      tepidariorum (43%) and also for the insects Locusta migratoria (45%), Drosophila
      melanogaster (42%) and Manduca sexta (47%) to vitellogenin 2 and tick Ixodes
      scapularis (83%), the crab Limulus polyphemus (55%) and the oyster Crassostrea
      gigas (55%) to vitellogenin 5. Furthermore, it shows a distinct lipid composition
      from most arthropod lipoproteins, being composed of 40% free cholesterol, 27%
      phospholipids, 20% triacylglycerol and 15% hydrocarbons. In addition to binding
      most hemolymphatic fatty acids, this lipoprotein also binds and transports free
      cholesterol. In conclusion, the present study provides insight into the
      macromolecules involved in arachnid metabolism, which have significant potential
      for future use for the biological control of ticks.

PMID- 29567148
TI  - Research on Piroplasmorida and other tick-borne agents: Are we going the right
      way?
AB  - The use of molecular diagnostic techniques in the study of ticks and tick-borne
      agents has increased dramatically in the last few decades, and while conferring
      the advantages of rapidity, sensitivity and accuracy, they can also be misused by
      the research community, who have shown an increasing overreliance on the data
      they produce, often completely abandoning more traditional approaches such as
      microscopy and serology. In this short review examples are provided of 'findings'
      that are apparently at odds with well-established eco-epidemiological knowledge,
      ranging from descriptions of new species of pathogens to their detection in new
      hosts and ticks, often immediately incriminated as new reservoir hosts and vector
      ticks, respectively. Most examples have been taken from the Piroplasmorida or
      "piroplasm" species as they are often called. Researchers are urged to utilize
      molecular methods with as much awareness as possible of the system or systems
      they are investigating, and journal editors and their teams of reviewers should
      be encouraged to adopt a more critical approach to papers that contain data based
      solely on molecular methods without due regard to the underlying biology.
      Explanations for such findings should be offered and discussed.

PMID- 29567147
TI  - Anaplasma species detected in Haemaphysalis longicornis tick from China.
AB  - Anaplasma are tick-borne obligatory intracellular bacteria, which infect humans
      and other animals. The Anaplasma species carried by ticks in China are not well
      studied. We collected 3145 questing Haemaphysalis longicornis ticks including 120
      larvae, 2460 nymphs and 565 adults from vegetation in Jiaonan County, Shandong
      Province, China from 2013 to 2015. All ticks were examined for the presence of
      Anaplasma species by nested PCR amplification of the 16S rRNA gene. For further
      differentiation of A. capra from A. centrale, gltA and msp2 genes were sequenced
      for A. capra. Three Anaplasma species were detected in the nymph and/or adult
      ticks with the minimum infection rate of ticks as follows: 1.55% for A. bovis,
      0.10% for A. phagocytophilum, and 0.03% for A. capra. These results indicated
      that the H. longicornis tick in Jiaonan County carried multiple Anaplasma
      species, which may be a challenge for public health in the studying area.

PMID- 29567149
TI  - Fabrication of a novel enzymatic electrochemical biosensor for determination of
      tyrosine in some food samples.
AB  - In this work, fabrication of a novel and ultrasensitive electrochemical biosensor
      based on immobilization of tyrosine hydroxylase onto palladium-platinum
      bimetallic alloy nanoparticles/chitosan-1-ethyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl) imide/graphene-multiwalled carbon nanotubes
      IL/glassy carbon electrode for determination of L-tyrosine in some high tyrosine
      foods including cheese, egg and yogurt was reported. Immobilization of tyrosine
      hydroxylase onto the surface of the biosensor was performed by cross-linking
      tyrosine hydroxylase and chitosan through the addition of glutaraldehyde.
      Enzymatic biosensors employ the affinity and selectivity of catalytically active
      proteins towards their target molecules and here, the tyrosine hydroxylase
      selectively catalyzes the conversion of tyrosine to levodopa which can be
      oxidized at lower potentials than tyrosine. The modifications were characterized
      by electrochemical impedance spectroscopy, cyclic voltammetry, energy dispersive
      X-ray spectroscopic and scanning electron microscopy. Under optimal conditions,
      the biosensor detected tyrosine in concentration ranges of 0.01 * 10-9 to 8.0 *
      10-9 mol L-1 and 8.0 * 10-9 to 160.0 * 10-9 mol L-1 with a limit of detection of
      0.009 * 10-9 mol L-1. The biosensor was able to selective determination of
      tyrosine even in the presence of common interferents therefore, the biosensor was
      highly selective. The biosensor also showed good operational stability,
      antifouling properties, sensitivity, repeatability and reproducibility.

PMID- 29567150
TI  - Application of CE-ICP-MS and CE-ESI-MS/MS for identification of Zn-binding
      ligands in Goji berries extracts.
AB  - The identification of groups of ligands binding metals is a crucial issue for the
      better understanding of their bioaccessibility. In the current study, we have
      intended an approach for identification of Zn-binding ligands based on using
      capillary electrophoresis combined with inductively coupled plasma mass
      spectrometry (CE-ICP-MS) and tandem electrospray ionization mass spectrometry (CE
      ESI-MS/MS). The approach, which featured the use of the coupling of capillary
      electrophoresis with inductively coupled plasma mass spectrometry allows to
      separate and observe zinc ions present in complexes with respect to their size
      and charge and to identify nine compounds with zinc isotopic profile. CE-ICP-MS
      provides us with information about presence of zinc species and elemental
      information about zinc distribution. CE-ESI-MS/MS provide us with information
      about the most favorable Zn binding ligands: amino acids, flavonols, stilbenoids,
      fenolic acids and carotenoids. The presented work is the continuation of previous
      studies based on using LC-ESI-MS/MS, though, now we presented a new solutions
      with the possibility of changing detectors without changing the separation
      techniques, what is important without re-optimizing the method. The new presented
      method allows to identify the zinc-binding ligands in shorter time.

PMID- 29567151
TI  - Amplified electrochemiluminescence detection of DNA based on novel quantum dots
      signal probe by multiple cycling amplification strategy.
AB  - In the present work, we designed a unique enzyme-aided multiple amplification
      strategy for sensitive electrochemiluminescence (ECL) detection of DNA by using
      the amplified gold nanoparticles (GNPS)-polyamidoamine (PAMAM)-CdSe quantum dots
      (QDs) signal probe. Firstly, the novel GNPS-PAMAM dendrimers nanostructure with
      good biocompatibility and electroconductibility contains many amino groups, which
      can load a large number of CdSe QDs to develop amplified ECL signal probe. Then,
      the presence of target DNA activated the enzyme-assisted polymerization strand
      displacement cycling reaction, and a large number of the hairpin template was
      opened. Subsequently, the opened stem further interacted with the capture hairpin
      (HP) DNA on the electrode, and the GNPS-PAMAM-CdSe signal probe hybridized with
      the exposed stem of the HP to trigger the second new polymerization reaction.
      Meanwhile, the first cycle was generating abundant DNA triggers which could
      directly open the template. As a result of the cascade amplification technique, a
      large number of CdSe QDs signal probe could be assembled on the electrode,
      generating much amplified ECL signal for sensitive detection of target DNA. Thus,
      this novel QDs-based amplified ECL strategy holds great promise for DNA detection
      and can be further exploited for sensing applications in clinical diagnostics.

PMID- 29567152
TI  - Gold nanoparticle-based 2'-O-methyl modified DNA probes for breast cancerous
      theranostics.
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulated diverse
      cellular processes including differentiation, proliferation, apoptosis,
      metabolism and signal transduction pathways. An increasing number of data
      suggested that miRNA-21 could be identified as diagnostic and therapeutic
      biomarker for breast cancer. Meanwhile, inhibiting the function of miRNA-21,
      resulting in cells growth inhibition and apoptotic cells death. To realize miRNA
      21detection and inhibition to diagnostic and therapeutic breast cancer cells, we
      developed gold nanoparticle-based 2'-O-methyl modified DNA probes (AuNP-2'-OMe
      DNA probes) for diagnostic and therapeutic breast cancer. Gold nanoparticles were
      functionalized with chemically modified miRNA-21 inhibitor to suppress the
      function of miRNA-21 for the therapeutic breast cancer, at the same time,
      fluorophore-labeled DNA molecules were hybridized with antimiRNA-21 for
      diagnostic breast cancer. The results showed that the 2'-O-methyl modified DNA
      can improve stability, increase binding affinity to target strands and enhance
      the therapeutic effects. The experimental results also demonstrated that antimiR
      21 were efficiently introduced into the cells and knocked down miRNA-21 to
      inhibit its function, leading to growth inhibition and apoptotic cells death. We
      prospected that chemically modified miRNA-21 inhibitor based on gold
      nanoparticles would be as a promising diagnostic and therapeutic platform for
      breast cancer clinically.

PMID- 29567153
TI  - A novel amperometric biosensor based on covalently attached multilayer assemblies
      of gold nanoparticles, diazo-resins and acetylcholinesterase for the detection of
      organophosphorus pesticides.
AB  - Using an ionic layer-by-layer self-assembly technique, colloidal gold
      nanoparticles (AuNPs) and diazo-resins (DAR) were immobilised on the surface of a
      p-aminobenzenesulfonic acid-modified glassy carbon electrode to form a matrix
      composite membrane for acetylcholinesterase (AChE) immobilisation. Photo
      sensitive DAR was used as the assembly interlayer to convert the ionic bond into
      a covalent bond to improve the biosensor stability. These fabrication processes
      were followed by electrochemical impedance spectroscopy and cyclic voltammetry to
      verify the membrane formation. Because of the introduction of AuNPs/DAR/AChE
      biofilms, the modified electrode exhibited excellent electron transfer mediation
      and electrical conductivity. In addition, it exhibited high sensitivity in the
      range of linear concentration from 1.0 * 10-8 to 1.0 * 10-12 g L-1 with the
      detection limit of 5.12 * 10-13 and 5.85 * 10-13 g L-1 for malathion and methyl
      parathion, respectively. More importantly, the presented biosensor considerably
      improved stability because the electrostatic interaction was converted into
      covalent bonds by UV irradiation. It is a simple, cheap and stable method for
      quantitative detection of organophosphorus pesticides, and this method may pave a
      way for the sensitive, simple detection of different analytes without the need of
      expensive instrumentation.

PMID- 29567154
TI  - Facile preparation and characterization of new green emitting carbon dots for
      sensitive and selective off/on detection of Fe3+ ion and ascorbic acid in water
      and urine samples and intracellular imaging in living cells.
AB  - Carbon dots (CDs) have gained great attention as multifunctional materials
      because of their interesting properties and general applicability. However, there
      are some reports for the preparation of highly luminescent green-emitting CDs (G
      CDs), although these reports seem not to be extensible. Herein, new G-CDs
      (quantum yield: 27.2%) were synthesized from a facile hydrothermal treatment of p
      aminosalicylic acid and ethylene glycol dimethacrylate as both carbon and
      nitrogen source and cross-linking agent, respectively. The chemical composition
      and optical properties of the as-prepared G-CDs were successfully investigated
      using transmission electron microscopy, atomic force microscopy, dynamic light
      scattering, X-ray diffraction, energy dispersive X-ray spectroscopy, Fourier
      transform infrared spectroscopy and fluorescence and UV-vis spectroscopies.
      Interestingly, the fluorescence intensity of G-CDs was selectivity quenched by
      Fe3+ in the range of 0.05-10.0 umol L-1, with a detection limit of 13.7 nmol L-1.
      Meanwhile, ascorbic acid found to reduce Fe3+ to Fe2+, thereby causing
      restoration of the fluorescence of G-CDs. The detection limit for ascorbic acid
      detection was estimated as 82.0 nmol L-1 over a linear range from 0.2 to 11.0
      umol L-1. Furthermore, the designed sensing platform was successfully utilized to
      the detection of Fe3+ and ascorbic acid in water and urine samples and to
      intracellular imaging without surface modification.

PMID- 29567155
TI  - Development and validation of a hydrophilic interaction liquid chromatography
      method for the quantitation of impurities in fixed-dose combination tablets
      containing rosuvastatin and metformin.
AB  - A hydrophilic interaction liquid chromatography method with diode array detection
      (HILIC-DAD) was developed and validated for the simultaneous determination of
      impurities in extended-release fixed-dose combination tablets containing
      rosuvastatin and metformin in a ratio 1:100. The analytes were separated by
      hydrophilic interaction liquid chromatography using an XBridge(r)-HILIC
      analytical column under isocratic elution. The mobile phase was composed of
      ammonium formate at 150 mM containing 0.05% diethylamine (pH 8.5)/acetonitrile,
      4/96 (v/v) and pumped at a flow rate of 0.5 mL min-1. Method validation was
      performed according to ICH guidelines. The calibration curves for rosuvastatin,
      metformin and their seven impurities showed good linearity (r > 0.994) within the
      calibration ranges tested. The intra- and inter-day R.S.D. values were less than
      4.5%, while the relative percentage error Er was less than 2.7% for all
      compounds. Accelerated stability studies performed under various stress
      conditions including hydrolysis, oxidation and heat proved the selectivity of the
      procedure. A run time of less than 25 min for each sample made it possible to
      analyze a large number of samples per day. The method is the first reported
      application of HILIC for the analysis of impurities in fixed-dose combination
      tablets containing rosuvastatin and metformin and it can be used for the quality
      control of these drugs.

PMID- 29567156
TI  - Mutual factor analysis for quantitative analysis by temperature dependent near
      infrared spectra.
AB  - Temperature dependent near infrared (NIR) spectroscopy has been developed for
      analyzing multi-component mixtures and understanding the molecular interactions
      in solutions. In this work, a chemometric method named as mutual factor analysis
      (MFA) was proposed for the analysis of temperature dependent NIR spectra. The
      method extracts the common spectral feature contained in the spectra of different
      temperature or different concentration. The relative quantity of the extracted
      spectral feature is proportional to the temperature or concentration. From the
      spectra of water-glucose mixtures, both the spectral variations induced by
      temperature and concentration are obtained and the variations are correlated with
      the inducements, respectively, in a very good linearity. Serum samples were used
      for validation of the method. An acceptable calibration model with a good
      correlation coefficient (R2 = 0.8639) was obtained for glucose measurement. The
      relative deviations of the measured concentrations from the calibration model are
      in the range of -18.7-8.52%, which are in a reasonable level for clinical uses.
      More importantly, the calculations are based on the spectral information of water
      that has interactions with the analyte. This provides a new way for quantitative
      analyses of bio-systems.

PMID- 29567157
TI  - Magnetic solid-phase extraction of non-steroidal anti-inflammatory drugs from
      environmental water samples using polyamidoamine dendrimer functionalized with
      magnetite nanoparticles as a sorbent.
AB  - A novel polyamidoamine dendrimer functionalized with Fe3O4 nanoparticles
      (Fe3O4@PAMAM) had been fabricated and used as magnetic solid-phase extraction
      (MSPE) adsorbent. The Fe3O4@PAMAM nanocomposites were characterized by X-ray
      powder diffraction, Fourier transform infrared spectroscopy, field-emission
      scanning electron spectroscopy, elemental analytical, and thermal gravimetric
      analysis. The MSPE method coupled with high-performance liquid chromatography
      with an ultraviolet detection system was applied for the separation/analysis of
      non-steroidal anti-inflammatory drugs (NSAIDs). Major parameters affecting the
      extraction efficiency of the selected drugs were optimized. Under optimal
      conditions, the enrichment factors for the proposed method were 701835. The
      linear range, limit of detection, correlation coefficient (r), and relative
      standard deviation (RSD) were found to be 0.15-500 ng mL-1, 0.050.08 ng mL-1,
      0.99320.9967, and 4.5-7.0% (n = 5, 0.2, 10 and 300 ng mL-1), respectively. The
      method was successfully applied to the determination of NSAIDs in the real water
      samples. The recoveries of spiked water samples were in the range of 93.6-98.9%
      with RSDs varying from 6.1% to 9.0%, showing the good accuracy of the method.

PMID- 29567158
TI  - Trace detection and photothermal spectral characterization by a tuneable thermal
      lens spectrometer with white-light excitation.
AB  - In the thermal lens experimental set-up we replaced the commonly employed pump
      laser by a halogen lamp, combined with an interference filter, providing a
      tuneable, nearly monochromatic pump source over the range of wavelengths 430-710
      nm. Counter-propagating pump and probe beams are used and a 1 mm path-length
      sample cell together with the interference filter makes an optical cavity,
      providing amplification of the thermal lens signal, which leads to enhancement of
      the measurement sensitivity, and enables detection of absorbances on the order of
      5 * 10-6. Amplified thermal lens signal allows us to replace the typical lock-in
      amplifier and digital oscilloscope with a silicon photodetector, Arduino, and a
      personal computer, offering the possibility for a compact, robust and portable
      device, useful for in-field absorption measurements in low concentration or
      weakly absorbing species. The use of a white light source for optical pumping, an
      interference filter for wavelength selection and direct diagnostic of the thermal
      lens signal increase the versatility of the instrument and simplifies
      substantially the experimental setup. Determination of Fe(II) concentrations at
      parts per billion levels was performed by the described white-light thermal lens
      spectrophotometer and the absorption spectrum for 50 MUgL-1 Fe(II)-1,10
      phenanthroline was well reproduced with an average measurement precision of 4%.
      The obtained limits of detection and quantitation of Fe(II) determination at 510
      nm are 3 ugL-1 and 11 ugL-1, respectively. The calibration curve was linear in
      the concentration range of LOQ-500 ugL-1 with reproducibility between 2% and 6%,
      confirming that this instrument provides good spectrometric capabilities such as
      high sensitivity, tuneability and good reproducibility. In addition, the
      versatility of the instrument was demonstrated by recording the photothermal
      spectrum of gold nanostructured material and determination of excitation
      wavelength with most efficient optical to thermal energy conversion, which
      differs considerably (cca 100 nm) from the absorption maximum of the investigated
      sample.

PMID- 29567159
TI  - A new colorimetric, near-infrared fluorescent probe for rapid detection of
      palladium with high sensitivity and selectivity.
AB  - A new type of colorimetric, fluorescent palladium (Pd) probe characterized with
      beaconing fluorescence signal in the quiet near-infrared (NIR) region (centered ~
      717 nm), recognition response time of approximately 3 min, limit of detection
      (LOD) down to 5.1 ppb, and excellent recognition specificity over a wide range of
      interfering metal cations was developed. It is believed that the probe underwent
      sequential Pd0-mediated oxidative addition and reduction elimination reactions,
      yielding typical D-pi-A molecular skeleton of the final reaction product capable
      of intramolecular charge transfer (ICT). The benzothiazole moiety of the probe
      molecular skeleton is believed to play a vital trole in shifting the beaconing
      fluorescence signal to the quiet NIR region and accelerating the Pd0 recognition
      process of the probe via the formation of the fluorescent reaction product with
      largely extended pi-delocalization. With unique advantages, the fluorescent probe
      we developed will find practical applications for detecting residual Pd with
      concentration below the safety margin in pharmacy and biomedical engineering.

PMID- 29567160
TI  - Flow based determination of Cr(VI) by adsorptive cathodic stripping voltammetry
      on an immobilized magnetic poly(ionic liquid) modified electrode.
AB  - In this work an electrochemical procedure for Cr(VI) flow based determination in
      tap water is presented. An AdCSV method was developed using a screen printed
      electrode modified with magnetic poly(1-allyl-3-methylimidazolium) chloride and
      the procedure does not require the addition of complexing agents in the solution
      unlike the methodologies reported so far for Cr(VI) determination. The flow based
      system is described and the control variables were studied in detail and
      optimized using a Taguchi parameters design. Under optimal conditions, the
      electrochemical sensor offered an excellent response to Cr(VI) and the limit of
      detection estimated from 3sigma was 0.5 ug L-1 (n = 3) allowing the analysis of
      tap water samples. The effect of interfering ions was also investigated below the
      maximum permissible limits for tap water according to Mexican standards. The
      presence of the magnetic particles on the sorbent allowed its easy modification
      on the electrode surface between each determination when removing the magnetic
      field placed in the wall-jet cell. Finally, the precision of the method was
      tested with tap water samples using standard addition method for Cr(VI)
      quantification and the accuracy was evaluated comparing the results with the
      dyphenylcarbazide method and by analyzing a certified water sample. The method
      shows good repeatability and reproducibility (%RSD less than 5%) making it
      feasible for Cr(VI) flow based determination and no significant difference is
      observed in the results obtained by both methods.

PMID- 29567161
TI  - Analysis of isomeric opioids in urine using LC-TIMS-TOF MS.
AB  - In the present work, a fast separation, identification and quantification
      workflow based on liquid chromatography coupled to trapped ion mobility in tandem
      with mass spectrometry (LC-TIMS-MS) is described for the analysis of common
      isomeric drugs of abuse and their metabolites in human urine. In particular, the
      analytical performance of LC-TIMS-MS is shown for identification based on
      retention time, collision cross section and accurate mass for three sets of
      common isomeric opioids and their deuterated analogs in urine. The LC-TIMS-MS
      analysis provided limits of detection of 1.4-35.2 ng/mL with demonstrated
      linearity up to 500 ng/mL, enabling discovery and targeted monitoring (DTM) of
      opioids in urine, with high precision in retention times (RT) (< 0.3%), collision
      cross sections (CCS) (< 0.6%) and mass accuracy (< 1 ppm) across multiple
      measurements using external calibration. A good agreement was observed between
      theoretical and experimental CCS from candidate structures optimized at the
      DFT/B3LYP level. The need for complementary liquid and mobility separations prior
      to mass analysis is shown for the analysis of complex mixtures, with mobility
      resolving power of 80-130. The reproducibility and high speed of LC-TIMS-MS
      analysis provides a powerful platform for drug and metabolite screening in
      biological matrices with higher precision and confidence than traditional LC
      multiple reaction monitoring (MRM) approaches.

PMID- 29567162
TI  - Direct measurement of uranium in seawater by inductively coupled plasma mass
      spectrometry.
AB  - A simple method for direct measurement of uranium (238U) in seawater using triple
      quadrupole inductively coupled plasma mass spectrometry (ICP-MS) was established.
      The method provides a good analytical performance with respect to detection
      limit, accuracy, precision and sample throughput. During the method development
      and application, several interesting facts were observed: 1) Comparison results
      for reference material using different quantitation approaches indicate that
      isotope dilution (using 233U) is the most reliable to achieve accurate 238U
      measurement. The results obtained for direct 238U measurement in 50-fold diluted
      seawater samples (n = 112) also underline the difference between isotope dilution
      and internal (or external) standardization. 2) Appropriate dilution of seawater
      is important to minimize the matrix effect on the ICP-MS measurement and 20-50
      dilution is recommended for natural seawater samples. 3) The sensitivity of ICP
      MS was observed to increase in the beginning of sample measurement, and then
      decrease with the continuous injection of samples, which is believed as a
      consequence of matrix effect from the seawater to the ionization efficiency in
      the plasma. 4) When measuring samples taken from large volume of seawater stored
      in immovable containers for relatively long period (i.e., several months), the
      uranium concentration and salinity data showed slightly increasing trends with
      the increase of water depth in the container. Therefore, cautions need to be paid
      in sampling representativeness when performing 238U measurement for such long
      term stored large volume samples.

PMID- 29567163
TI  - Simultaneous determination of copper and zinc in brass samples by PCR and PLS1
      methods using a multiple ion-selective electrode array.
AB  - A method was developed to determine copper and zinc simultaneously in brass
      sample using a multiple ion-selective electrode array system and multivariate
      calibration techniques. The multiple ion-selective electrode array system was
      consisted of one pH electrode and eight ion selective electrodes which were
      formed using commercial ionophores and which are mainly sensitive copper and
      zinc. PCR, PLS1 which are multivariate calibration techniques were used to
      calibrate the multiple ion-selective electrode array system using five level
      multivariate calibration design and PCR method was selected as most suitable
      method. The measurements were performed at pH 10 in ammonia-ammonium chloride
      buffer. Copper and zinc content of a brass sample were determined by the
      calibrated multiple ion-selective electrode array system and the composition of
      brass sample was also determined by gravimetric method. The percentage amount of
      copper and zinc in brass sample were 64 +/- 1 and 26 +/- 2, respectively using
      the gravimetric method. The percentage results obtained in brass samples for
      copper and zinc were 63 +/- 3 and 24 +/- 3 by PCR method and 60 +/- 5 and 20 +/-
      7 by PLS1 method, respectively. The obtained results were calculated for a 95%
      confidence level.

PMID- 29567164
TI  - A vertical flow paper-microarray assay with isothermal DNA amplification for
      detection of Neisseria meningitidis.
AB  - Paper-based biosensors offer a promising technology to be used at the point of
      care, enabled by good performance, convenience and low-cost. In this article, we
      describe a colorimetric vertical-flow DNA microarray (DNA-VFM) that takes
      advantage of the screening capability of DNA microarrays in a paper format
      together with isothermal amplification by means of Recombinase Polymerase
      Amplification (RPA). Different assay parameters such as hybridization buffer,
      flow rate, printing buffer and capture probe concentration were optimized. A
      limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop
      scanning. The DNA-VFM was applied as a proof of concept for detection of
      Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was
      determined to be between 38 and 2.1 * 106 copies/VFMassay, depending on the
      choice of DNA capture probes. The presented approach provides multiplex
      capabilities of DNA microarrays in a paper-based format for future point-of-care
      applications.

PMID- 29567165
TI  - 3D-printed lab-on-valve for fluorescent determination of cadmium and lead in
      water.
AB  - In recent years, the development of 3D printing in flow analysis has allowed the
      creation of new systems with various applications. Up to now, 3D printing was
      mainly used for the manufacture of small units such as flow detection cells,
      preconcentration units or mixing systems. In the present study, a new 3D printed
      lab-on-valve system was developed to selectively quantify lead and cadmium in
      water. Different technologies were compared for lab-on-valve 3D printing. Printed
      test units have shown that stereolithography or digital light processing are
      satisfactory techniques for creating complex lab-on-valve units. The lab-on-valve
      system was composed of two columns, eight peripheral ports and a central port,
      and a coil integrating baffles to increase mixing possibilities. A selective
      extraction of lead was first carried out by TrisKem PbTM Resin column. Then,
      cadmium not retained on the first column was extracted on a second column of
      Amberlite(r) IR 120 resin. In a following step, lead and cadmium were eluted with
      ammonium oxalate and potassium iodide, respectively. Finally, the two metals were
      sequentially detected by the same Rhod-5NTM fluorescent reagent. This 3D printed
      lab-on-valve flow system allowed us to quantify lead and cadmium with a linear
      response from 0.2 to 15 ug L-1 and detection limits of 0.17 and 0.20 ug L-1 for
      lead and cadmium, respectively, which seems adapted for natural water analysis.

PMID- 29567166
TI  - Assessment of a colorimetric method for the measurement of low concentrations of
      peracetic acid and hydrogen peroxide in water.
AB  - The recent growing interest in peracetic acid (PAA) as disinfectant for
      wastewater treatment demands reliable and readily-available methods for its
      measurement. In detail, the monitoring of PAA in wastewater treatment plants
      requires a simple, accurate, rapid and inexpensive measurement procedure. In the
      present work, a method for analyzing low concentrations of PAA, adapted from the
      US EPA colorimetric method for total chlorine, is assessed. This method employs
      N,N-diethyl-p-phenylelnediamine (DPD) in the presence of an excess of iodide in a
      phosphate buffer system. Pink colored species are produced proportionally to the
      concentration of PAA in the sample. Considering that PAA is available
      commercially as an equilibrium solution of PAA and hydrogen peroxide (H2O2), a
      measurement method for H2O2 is also investigated. This method, as the one for the
      determination of PAA, is also based on the oxidation of iodide to iodine, with
      the difference that ammonium molybdate Mo(VI) is added to catalyze the oxidation
      reaction between H2O2 and iodide, quantifying the total peroxides (PAA+ H2O2).
      The two methods are suitable for concentration ranges from about 0.1-1.65 mg L-1
      and from about 0.3-3.3 mg L-1, respectively for PAA and H2O2. Moreover, the work
      elucidates some relevant aspects related to the operational conditions, kinetics
      and the possible interference of H2O2 on PAA measurement.

PMID- 29567167
TI  - Update on thalassemia diagnosis: New insights and methods.
AB  - A novel approach based on Thermogravimetric analysis followed by Chemometrics
      (TGA/Chemometrics) is provided for Thalassemia diagnosis and a comprehensive
      study consisting of the coupled approach TGA/Chemometrics, the Complete Blood
      Count (CBC) and Red Blood Cell (RBC) indices is developed and results are
      compared. A number of 128 subjects were involved in this study included 16
      thalassemia intermedia transfusion-dependent (TI-TD) patients, 18 thalassemia
      intermedia non transfusion-dependent (TI-NTD) patients, and 14 thalassemia major
      beta (TM-TD) patients. Thalassemic patients were found to be clearly distinct
      from healthy donors as a function of a different thermal behavior. The
      chemometric analysis identifies the differences in the composition of blood and a
      model of prediction for beta-thalassemia was developed and validated to
      distinguish all patients. TGA/Chemometrics method also permitted to differentiate
      thalassemic patients according to the severity of anaemia while the evaluation of
      the indices and the CBC are not able to identify TI-TD, TI-NTD and TM-TD patients
      at first level test. TGA/Chemometrics was successfully applied for thalassemia
      diagnosis with 100% of correct classification rate. Chemometric analysis
      demonstrated that red cell distribution width (RDW), haemoglobin (Hb) and RBC are
      the diagnostic features in thalassemia compared to mean corpuscular volume (MCV)
      and mean corpuscular haemoglobin (MCH). New insights into the significance of the
      haematological features were provided for an update of the thalassemia
      classification.

PMID- 29567168
TI  - Simple and label-free liquid crystal-based sensor for detecting trypsin coupled
      to the interaction between cationic surfactant and BSA.
AB  - Trypsin plays a central role in catalyzing the hydrolysis of peptide bonds, so a
      technique with simple operation is needed to monitor the activity of trypsin.
      Here a simple and label-free senor based on liquid crystals (LCs) was developed
      by employing bovine serum albumin (BSA) as the enzyme substrate and dodecyl
      trimethyl ammonium bromide (DTAB) as the controller for the alignment of LC. It
      was found that DTAB could form a self-assembled monolayer at the aqueous/LC
      interface to produce the dark optical images of LCs. And the addition of BSA
      could disturb the monolayer, so that the optical signal of LCs turned bright from
      dark. But the hydrolysis of BSA by trypsin resulted in the dark appearance. The
      sensing platform allows detection as low as 1 U/mL under the polarized light
      microscope based on at least three measurements. Moreover, this method was
      successfully applied in the detection of trypsin in human urines, suggesting its
      potential applications in clinic diagnosis.

PMID- 29567169
TI  - Complexometric and argentometric titrations using thread-based analytical
      devices.
AB  - This work describes analytical approaches based on simple complexometric and
      argentometric titrations leading to the color change of a novel microfluidic
      thread-based analytical device (uTAD). The device was fabricated from a cotton
      thread (15 cm) treated with indicator solution, providing an easy-to-use platform
      for rapid measurement of analyte concentration in aqueous solution. The thread
      was immobilized onto a support, being a polypropylene sheet or box platform, to
      facilitate loading of liquid samples. Interaction between the deposited reagents
      and analytes in the samples then occurred within a few minutes. This resulted in
      zones of color change with different lengths along the thread depending on the
      analyte concentration. The interaction zones can be analyzed by human eyes based
      on comparison of the zone lengths with the printed scales which are correlated
      with the analyte concentrations. Complexometric titration using uTADs was
      initially investigated for Mg(II) determination in water and rubber latex
      samples. These devices consisted of two threads which were pretreated with
      Eriochrome Black T (EBT) and then treated with ethylenediaminetetraacetic acid
      (EDTA) in N-cyclohexyl-3-aminopropanesulfonic acid (CAPS) buffer at pH 10. Both
      threads were tied together with a central knot before being attached to the box
      platform prior to the analysis. Load of sample solution (6 uL) resulted in the
      length of red-violet color product on the threads being proportional to the
      concentration of Mg(II) in waters and rubber latex samples with the working
      concentration range of 25-1000 mg L-1. In addition, uTAD with a supporting
      polypropylene sheet consisting of several threads treated with AgNO3 and K2CrO4
      indicators was applied for argentometric titration of chloride ion in water and
      food seasoning samples. After sample loading (3 uL), the initially red-brown
      threads turned into white corresponding to formation of AgCl(s) on the threads
      with a working concentration range of 75-600 mg L-1. Greater selectivity towards
      Mg(II) and chloride compared with potential interference ions was also observed.
      All the developed MUTADs were applied for analysis of real samples which showed
      results being in agreement with those obtained by classical titrations.

PMID- 29567170
TI  - Ultrasensitive photoelectrochemical aptasensor for lead ion detection based on
      sensitization effect of CdTe QDs on MoS2-CdS:Mn nanocomposites by the formation
      of G-quadruplex structure.
AB  - An ultrasensitive photoelectrochemical (PEC) aptasensor for lead ion (Pb2+)
      detection was fabricated based on MoS2-CdS:Mn nanocomposites and sensitization
      effect of CdTe quantum dots (QDs). MoS2-CdS:Mn modified electrode was used as the
      PEC matrix for the immobilization of probe DNA (pDNA) labeled with CdTe QDs.
      Target DNA (tDNA) were hybridized with pDNA to made the QDs locate away from the
      electrode surface by the rod-like double helix. The detection of Pb2+ was based
      on the conformational change of the pDNA to G-quadruplex structure in the
      presence of Pb2+, which made the labeled QDs move close to the electrode surface,
      leading to the generation of sensitization effect and evident increase of the
      photocurrent intensity. The linear range was 50 fM to 100 nM with a detection
      limit of 16.7 fM. The recoveries of the determination of Pb2+ in real samples
      were in the range of 102.5-108.0%. This proposed PEC aptasensor provides a new
      sensing strategy for various heavy metal ions at ultralow levels.

PMID- 29567171
TI  - Determination of fermentable sugars in beer wort by gold
      nanoparticles@polydopamine: A layer-by-layer approach for Localized Surface
      Plasmon Resonance measurements at fixed wavelength.
AB  - Polydopamine decorated in-situ with Localized Surface Plasmon Resonance (LSPR)
      active gold nanoparticles (AuNPs) may extend the applicability of nanoplasmonic
      materials to original and innovative applications in several fields. Here we
      report the modification of disposable UV-Vis polystyrene cuvettes with AuNPs@PDA
      for refractive index LSPR-based measurements. An original layer-by-layer
      deposition method of PDA followed by AuNPs growth is here developed, showing
      linear correlation between PDA thickness and optical properties. In particular,
      the modulation from wavelength sensitivity toward absorbance sensitivity is
      obtained, allowing measurements at fixed wavelength (578 nm). As applicative
      example of the photonic cuvettes, the measurement of fermentable sugars in beer
      wort is here reported. The analytical performance of our approach has been
      directly compared to portable refractometer of reference, displaying excellent
      results in terms of the precise estimation of sugars in beer wort (expressed in
      degrees Brix), reproducibility and sensitivity. The approach may be extended to
      other materials of interest in LSPR based optical sensors, e.g. optical fibers.

PMID- 29567172
TI  - Saliva as a source of new phosphopeptide biomarkers: Development of a
      comprehensive analytical method based on shotgun peptidomics.
AB  - The paper describes the development of an enrichment method for the analysis of
      the endogenous phosphopeptides in saliva. The method was based on magnetic solid
      phase extraction by a magnetic graphitized carbon black-TiO2 composite material
      and was developed considering different saliva pre-treatments, namely C18 solid
      phase extraction for purification, direct dilution in loading buffer or
      acetonitrile precipitation. The method was based on a shotgun proteomics workflow
      and the enriched peptide mixture was analysed by nanoHPLC and high resolution
      tandem mass spectrometry. Acetonitrile precipitation provided the best results,
      with up to 165 endogenous phosphopeptides identified in saliva samples from
      healthy individuals. The physico-chemical features of the identified endogenous
      phosphopeptides indicated that such peptides were large, hydrophilic and basic.

PMID- 29567173
TI  - A high throughput method for measuring cloth-air equilibrium distribution ratios
      for SVOCs present in indoor environments.
AB  - Accumulation of chemicals from the environment to clothing and other textiles can
      influence human uptake by several exposure routes. In this research, we
      demonstrate that the cloth-air equilibrium distribution ratio for species i,
      KCA_i, can be measured relatively easily and quickly using headspace analysis of
      cloth dosed with two common indoor air SVOCs, diethyl phthalate (DEP) and di-n
      butyl phthalate (DnBP). A known mass of a phthalate was applied to the cloth in a
      volatile solvent carrier. After evaporation of the solvent, the cloth was placed
      in a vial and allowed to equilibrate with the air in the vial. Since the volume
      of headspace air is small, the total mass required to transfer from cloth to air
      is small and also the time required for air equilibration with the fabric surface
      is very short (minutes). Distribution ratios for the two phthalate esters sorbed
      to cotton jean material, reported as the concentration in the bulk cloth divided
      by the air concentration, were measured at 20, 25, 32, and 40  degrees C. The
      volume-normalized distribution ratio, Kvol [(MUg/m3)/(MUg/m3)], ranged from (0.75
      +/- 0.01)* 105 to (5.6 +/- 0.2) * 105 for DEP and (5 +/- 0.3)* 105 to (57 +/- 1)
      * 105 for DnBP. Mass-normalized distribution ratio, Kmass [m3/g], ranged from
      (0.25 +/- 0.01) to (1.8 +/- 0.1) for DEP and (1.6 +/- 0.1) to (18.5 +/- 0.5) for
      DnBP. The cloth-air distribution ratios obtained from this study compare
      favorably with previously published results using other methods. Although
      equilibration with air in the headspace can be rapid, diffusion into the textile
      fibers is a slower equilibration process. Overall, this simple method has the
      potential to rapidly generate distribution ratios for a large number of chemical
      textile pairs.

PMID- 29567174
TI  - Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing
      acetylcholinesterase activity and its inhibitors.
AB  - A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine
      Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking
      nanowire, was constructed to detect acetylcholinesterase (AChE) activity and
      screen its inhibitors. This sensing strategy involves the reaction of
      acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline
      that is in turn catalytically oxidized by choline oxidase (ChOx) to produce
      hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic
      property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform
      was capable of investigating successive of H2O2 effectively by amperometric i-t
      (current-time) response, and was further applied for the turn-on electrochemical
      detection of AChE activity. The proposed sensor is highly sensitive (limit of
      detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The
      model for AChE inhibition was further established and two traditional AChE
      inhibitors (donepezil and tacrine) were employed to verify the feasibility of the
      system. The IC50 of donepezil and tacrine were estimated to be 1.4 nM and 3.5 nM,
      respectively. The developed protocol provides a new and promising platform for
      probing AChE activity and screening its inhibitors with low cost, high
      sensitivity and selectivity.

PMID- 29567175
TI  - Ligand-assisted magnetic solid phase extraction for fast speciation of silver
      nanoparticles and silver ions in environmental water.
AB  - In this work, poly(1-vinylimidazole) functionalized magnetic nanoparticles (PVIM
      MNPs) were prepared and adopted for the adsorption of silver nanoparticles
      (AgNPs) and silver ions (Ag ions). With the use of mercaptosuccinic acid as a
      ligand exchanger, both of AgNPs and Ag ions could be adsorbed on the PVIM-MNPs
      and the sequential desorption of Ag ions and AgNPs was easily achieved by using
      Na2S2O3 and HNO3, respectively. Based on it, a new approach by coupling ligand
      assisted magnetic solid phase extraction (MSPE) with graphite furnace atomic
      absorption spectrometry (GFAAS) detection was proposed for the speciation of
      AgNPs and Ag ions in environmental water samples. Factors affecting MSPE of AgNPs
      and Ag ions were investigated and the optimized conditions were established. With
      an enrichment factor of 100-fold, the detection limits of the proposed method
      were 7.5 and 8.2 ng L-1 for Ag ions and AgNPs with relative standard deviations
      of 6.4% and 7.0% (c = 50 ng L-1, n = 7), respectively. The proposed ligand
      assisted MSPE-GFAAS method has the advantages of high sensitivity, low cost and
      easy operation, and could be used for the quantification of Ag ions and various
      coating modified AgNPs with a size range of 5-120 nm in environmental waters.

PMID- 29567176
TI  - Direct solid phase microextraction combined with gas chromatography - Mass
      spectrometry for the determination of biogenic amines in wine.
AB  - A direct method based on immersion solid phase microextraction (DI-SPME) gas
      chromatography mass-spectrometry (GC-MS) was optimized and validated for the
      determination of 16 biogenic amines in Polish wines. In the analysis two internal
      standards were used: 1,7-diaminoheptane and bis-3-aminopropylamine. The method
      allows for simultaneous extraction and derivatization, providing a simple and
      fast mode of extraction and enrichment. Different parameters which affect the
      extraction procedure were studied and optimized including ionic strength (0-25%),
      fiber materials (PDMS/DVB, PDMS/DVD + OC, Polyacrylate, Carboxen/PDMS and
      DVB/CAR/PDMS) and timings of the extraction, derivatization and desorption
      processes. Validation studies confirmed the linearity, sensitivity, precision and
      accuracy of the method. The method was successfully applied to the analysis of 44
      wine samples originating from several regions of Poland and 3 wine samples from
      other countries. Analysis showed that many of the samples contained all examined
      biogenic amines. The method, assessed using an Eco-Scale tool with satisfactory
      results, was found to be green in terms of hazardous chemicals and solvents
      usage, energy consumption and production of waste. Therefore the proposed method
      can be safely used in the wine industry for routine analysis of BAs in wine
      samples with a minimal detrimental impact on human health and the environment.

PMID- 29567177
TI  - Quantitative determination of total cesium in highly active liquid waste by using
      liquid electrode plasma optical emission spectrometry.
AB  - A sensitive analytical method for determination of total cesium (Cs) in highly
      active liquid waste (HALW) by using modified liquid electrode plasma optical
      emission spectrometry (LEP-OES) is developed in this study. The instrument is
      modified to measure radioactive samples in a glove box. The effects of important
      factors, including pulsed voltage sequence and nitric acid concentration, on the
      emission of Cs are investigated. The limit of detection (LOD) and limit of
      quantification (LOQ) are 0.005 mg/L and 0.02 mg/L, respectively. The achieved LOD
      is one order lower than that of recently developed spectroscopic methods using
      liquid discharge plasma. The developed method is validated by subjecting a
      simulated HALW sample to inductively coupled plasma mass spectrometry (ICP-MS).
      The recoveries obtained from a spike-and-recovery test are 96-102%, implying good
      accuracy. The method is successfully applied to the quantification of Cs in a
      real HALW sample at the Tokai reprocessing plant in Japan. Apart from dilution
      and filtration of the HALW sample, no other pre-treatment process is required.
      The results agree well with the values obtained using gamma spectrometry. The
      developed method offers a reliable technique for rapid analysis of total Cs in
      HALW samples.

PMID- 29567178
TI  - A paper-based analytical device for the determination of hydrogen sulfide in fuel
      oils based on headspace liquid-phase microextraction and cyclic voltammetry.
AB  - An easily performed miniaturized, cheap, selective and sensitive procedure for
      the determination of H2S in fuel oil samples based on a headspace liquid-phase
      microextraction followed by a cyclic voltammetry detection using a paper-based
      analytical device (PAD) was developed. A modified wax dipping method was applied
      to fabricate the PAD. The PAD included hydrophobic zones of sample and supporting
      electrolyte connecting by hydrophilic channel. The zones of sample and supporting
      electrolyte were connected with nickel working, platinum auxiliary and Ag/AgCl
      reference electrodes. The analytical procedure included separation of H2S from
      fuel oil sample based on the headspace liquid-phase microextraction in alkaline
      solution. Then, sulfide ions solution obtained and supporting electrolyte were
      dropped on the zones followed by analyte detection at + 0.45 V. Under the
      optimized conditions, H2S concentration in the range from 2 to 20 mg kg-1 had a
      good linear relation with the peak current. The limit of detection (3sigma) was
      0.6 mg kg-1. The procedure was successfully applied to the analysis of fuel oil
      samples.

PMID- 29567179
TI  - A 3D-printed self-propelled, highly sensitive mini-motor for underwater pesticide
      detection.
AB  - A three-dimensionally printed self-propelled mini-motor (SPM) for the detection
      of underwater pollutants is proposed. The device uses highly sensitive metal
      nanoparticles for colorimetric monitoring. Gold nanoparticles covered with
      Rhodamine B (RB-AuNPs) were prepared, based on established colorimetric and
      fluorometric approaches for detecting pesticides. The detection mechanism
      monitors the inhibition of the activity of acetylcholinesterase (AChE) by the
      pesticide, in which the production of thiocholine from the hydrolysis of
      acetylthiocholine (ATCh) catalyzed by AChE is reduced. As a result, the color of
      the RB-AuNP solution remains red, and the fluorescence of RB remains quenched.
      The RB-AuNPs were characterized by transmission electron microscopy (TEM), UV-Vis
      absorption spectroscopy, and X-ray photoelectron spectroscopy (XPS). Under the
      optimized experimental conditions, excellent reproducibility (with a relative
      standard deviation of 5.8%) and low sensitivity limits, ranging from 0.4 to 3.0
      MUg L-1, were achieved. The limit of quantity (LOQ) was 0.3 MUg L-1,and the
      detection limit (LOD) was 0.23 MUg L-1, which was much lower than the maximum
      residue limits reported in the European Union pesticide database. With the aid of
      3D-printed SPMs and nano-colorimetry, both qualitative and quantitative analyses
      can be performed for pesticide detection in river water. This is the first time a
      3D-printed SPM has been combined with nano-colorimetry to realize a convenient,
      cost-effective, and high sensitive detection method for pollutants in water.

PMID- 29567180
TI  - Equilibrium ex vivo calibration of homogenized tissue for in vivo SPME
      quantitation of doxorubicin in lung tissue.
AB  - The fast and sensitive determination of concentrations of anticancer drugs in
      specific organs can improve the efficacy of chemotherapy and minimize its adverse
      effects. In this paper, ex vivo solid-phase microextraction (SPME) coupled to LC
      MS/MS as a method for rapidly quantitating doxorubicin (DOX) in lung tissue was
      optimized. Furthermore, the theoretical and practical challenges related to the
      real-time monitoring of DOX levels in the lung tissue of a living organism (in
      vivo SPME) are presented. In addition, several parameters for ex vivo/in vivo
      SPME studies, such as extraction efficiency of autoclaved fibers,
      intact/homogenized tissue differences, critical tissue amount, and the absence of
      an internal standard are thoroughly examined. To both accurately quantify DOX in
      solid tissue and minimize the error related to the lack of an internal standard,
      a calibration method at equilibrium conditions was chosen. In optimized ex vivo
      SPME conditions, the targeted compound was extracted by directly introducing a 15
      mm (45 um thickness) mixed-mode fiber into 15 g of homogenized tissue for 20 min,
      followed by a desorption step in an optimal solvent mixture. The detection limit
      for DOX was 2.5 ug g-1 of tissue. The optimized ex vivo SPME method was
      successfully applied for the analysis of DOX in real pig lung biopsies, providing
      an averaged accuracy and precision of 103.2% and 12.3%, respectively.
      Additionally, a comparison between SPME and solid-liquid extraction revealed good
      agreement. The results presented herein demonstrate that the developed SPME
      method radically simplifies the sample preparation step and eliminates the need
      for tissue biopsies. These results suggest that SPME can accurately quantify DOX
      in different tissue compartments and can be potentially useful for monitoring and
      adjusting drug dosages during chemotherapy in order to achieve effective and safe
      concentrations of doxorubicin.

PMID- 29567181
TI  - Electrochemical detection of c-reactive protein based on anthraquinone-labeled
      antibody using a screen-printed graphene electrode.
AB  - In this present work, a novel electrochemical immunosensor employing a screen
      printed graphene electrode (SPGE) for a simple and highly sensitive determination
      of C-reactive protein (CRP) in a sandwich-type format was proposed. The sensor
      comprised of two CRP-specific antibodies: an unlabeled capture primary antibody
      (Anti-1 degrees Ab) and an electrochemically detectable anthraquinone-labeled
      signaling secondary (AQ-2 degrees Ab) antibody. The Anti-1 degrees Ab was first
      covalently anchored onto an L-cysteine/gold-modified disposable SPGE (L
      Cys/Au/SPGE) to create the anti-CRP surface. After binding of the CRP and the AQ
      2 degrees Ab, the electrochemical signal response was measured using differential
      pulse voltammetry (DPV). In the presence of CRP, the sensor exhibited a
      significant increase in the AQ current at AQ-2 degrees Ab compared to the
      negative control. The CRP concentration was detected in the range of 0.01-150
      ug/mL, and the limit of detection (LOD) (S/N = 3) and limit of quantitation (LOQ)
      (10 SD/Slope) were 1.5 ng/mL and 10 ng/mL, respectively. This sensor exhibited
      very high sensitivity in determining CRP and was successfully applied to detect
      CRP in certified human serum with satisfactory results. The developed sensor is
      suitable as an alternative method for determination of CRP and the same principle
      may be further applied to determine other clinically important target molecules.

PMID- 29567182
TI  - Assessment of infant formula quality and composition using Vis-NIR, MIR and Raman
      process analytical technologies.
AB  - In this study, visible and near-infrared (Vis-NIR), mid-infrared (MIR) and Raman
      process analytical technologies were investigated for assessment of infant
      formula quality and compositional parameters namely preheat temperature, storage
      temperature, storage time, fluorescence of advanced Maillard products and soluble
      tryptophan (FAST) index, soluble protein, fat and surface free fat (SFF) content.
      PLS-DA models developed using spectral data with appropriate data pre-treatment
      and significant variables selected using Martens' uncertainty test had good
      accuracy for the discrimination of preheat temperature (92.3-100%) and storage
      temperature (91.7-100%). The best PLS regression models developed yielded values
      for the ratio of prediction error to deviation (RPD) of 3.6-6.1, 2.1-2.7, 1.7
      2.9, 1.6-2.6 and 2.5-3.0 for storage time, FAST index, soluble protein, fat and
      SFF content prediction respectively. Vis-NIR, MIR and Raman were demonstrated to
      be potential PAT tools for process control and quality assurance applications in
      infant formula and dairy ingredient manufacture.

PMID- 29567183
TI  - Simultaneous determination of isoproterenol, acetaminophen, folic acid,
      propranolol and caffeine using a sensor platform based on carbon black, graphene
      oxide, copper nanoparticles and PEDOT:PSS.
AB  - We explored the use of carbon black (CB), graphene oxide (GO), copper
      nanoparticles (CuNPs) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)
      (PEDOT:PSS) as electrode materials for the simultaneous determination of
      isoproterenol, acetaminophen, folic acid, propranolol and caffeine. The designed
      nanostructured surface was widely characterized by scanning electron microscopy
      (SEM), energy dispersive spectroscopy (EDS), contact angle measurements and
      electrochemistry. From electrochemical characterization assays carried out
      towards the potassium ferricyanide redox probe, fast electron transfer kinetics
      and a considerably higher electroactive surface area were observed for the
      modified electrodic surface based on CB, GO, CuNPs and PEDOT:PSS film. Using
      square-wave voltammetry (SWV), well defined and resolved anodic peaks were
      detected for isoproterenol, acetaminophen, folic acid, propranolol and caffeine,
      with peak-to-peak potential separation not less than 170 mV. Then, the SWV
      technique was explored for the simultaneous determination of quinary mixtures of
      these analytes, resulting in analytical curves with linear ranges and limits of
      detection at micromolar concentration levels. The practical viability of the
      proposed voltammetric sensor was illustrated in the analysis of human body fluid
      samples. The proposed sensor showed good repeatability and a successful
      application using urine and serum matrices, with recoveries close to 100%.

PMID- 29567184
TI  - Dual detection for non-aqueous capillary electrophoresis combining contactless
      conductivity detection and mass spectrometry.
AB  - Coupling of two detectors is a powerful tool to enhance the overall analytical
      performance generating complementary information and overcoming the limitations
      of the single detectors. In this work, capacitively coupled contactless
      conductivity detection (C4D) and electrospray ionization mass spectrometry (ESI
      MS) were coupled in conjunction with non-aqueous capillary electrophoresis
      (NACE). Non-aqueous electrolytes are highly compatible with ESI due to their
      volatility. Moreover, they exhibit low background conductivity, which is
      essential for the detection with C4D. A NACE-C4D-MS method was developed using an
      acetonitrile buffer containing 2 M HAc and 4 mM NH4Ac as background electrolyte.
      The influence of the inner diameter of the separation capillary on the C4D was
      studied and taken into account. A capillary with 50 um inner diameter was found
      to be best suited. The complementarity of the two detectors was shown by
      determining a sample mixture containing choline, thiamine, nitrate, and chloride
      as well as bromide and acetylcholine as internal standards. The C4D was the
      detector of choice for the inorganic ions, which were not detectable with the MS
      whereas the MS had much lower limits of detections for the organic biomolecules.
      The method was applied on an extract of a food supplement containing the model
      analytes.

PMID- 29567185
TI  - Nitrogen-doped graphene quantum dots-based fluorescence molecularly imprinted
      sensor for thiacloprid detection.
AB  - In this paper, a test strip-based sensor was developed for thiacloprid
      quantitative detection based on PDA molecularly imprinted polymer (MIP) and
      nitrogen-doped graphene quantum dots (N-GQDs). Thiacloprid is a new type of
      nicotine insecticide, which can block the normal neurotransmitter delivery
      process in insects. In the sensing system, N-GQDs were immersed into filter paper
      at first. Then, dopamine (DA) with thiacloprid can be self-polymerized on test
      strip surface to form the uniform PDA film. After removed thiacloprid template,
      the established poly dopamine (PDA) MIP can selectively recognize thiacloprid. As
      a result, captured thiacloprid can enhance the fluorescence intensity of N-GQDs
      into the test strip. As a result, the fluorescence intensity of N-GQDs can be
      linearly related within a certain range of thiacloprid concentration. Under the
      optimum conditions, the proposed sensor for thiacloprid detection exhibited a
      linear ranging from 0.1 mg/L to 10 mg/L with a low detection limit of 0.03 mg/L.
      The N-GQDs based test strip-based sensor for thiaclopridis reported for the first
      time. The sensing system has high selectivity to thiacloprid and provides new
      opportunities in the pesticide detection.

PMID- 29567186
TI  - Electrophoresis in ice surface grooves for probing protein affinity to a specific
      plane of ice crystal.
AB  - Channel-like grooves are formed on the surface of frozen aqueous sucrose. They
      are filled with a freeze concentrated solution (FCS) and act as an efficient size
      tunable separation field for micro and nanoparticles. The width of the channel
      can be easily varied by changing the temperature. Because the channel width
      decreases with decreasing temperature, particles become immobilized due to
      physical interference from the ice wall when the temperature reaches a threshold
      point specific to the particle size. Surface modification of particles can add a
      factor of chemical interaction between the particles and ice walls. In this
      study, anti-freeze proteins (AFPs) are anchored on 1um-polystyrene (PS)
      particles, and their behavior in the surface grooves on the ice is studied. The
      threshold temperature is an effective criterion for evaluating chemical
      interactions between particles and ice walls. The AFP binding on 1um PS particles
      lowers the threshold temperature by 2.5 degrees C, indicating interactions
      between AFPs on the PS particles and the ice wall. Because the AFPs studied here
      show selectivity towards the prism plane, it is critical that the prism plane of
      the ice crystal is in contact with the FCS in the surface grooves.

PMID- 29567187
TI  - Folic acid-conjugated green luminescent carbon dots as a nanoprobe for
      identifying folate receptor-positive cancer cells.
AB  - Early diagnosis is pivotal in subsequent prognosis and treatment of cancer.
      Herein, folic acid-conjugated carbon dots (FA-CDs) as a fluorescent nanoprobe
      were fabricated for identifying cancer cells visually. Green luminescent carbon
      dots (CDs) from active dry yeast (ADY) were readily prepared in scale-up to reach
      macroscopic production with a high yield of ~50% via a facile and rapid microwave
      approach. The as-prepared CDs were further combined with folic acid (FA) by
      covalent bonding to fabricate the FA-CDs for identification of cancer cells over
      expressing folate receptor (FR). Experimental outcomes demonstrated that the
      resultant FA-CDs noninvasively entered into cancer cells via receptor-mediated
      endocytosis and could differentiate FR-positive HepG2 cells from a cell mixture
      by fluorescence imaging, which suggests a promising prospect of the FA-CDs as an
      efficient probe for cancer diagnosis and succeeding personalized therapy.

PMID- 29567188
TI  - Arsenic speciation in tree moss by mass spectrometry based hyphenated techniques.
AB  - A method based on ion-pair reversed phase high performance liquid chromatography
      (HPLC) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) was
      developed for arsenic speciation in extract of tree moss. Under the optimal
      conditions, the limit of detection of eight arsenic species including arsenite
      (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsonic acid
      (DMA), trimethylarsinoxide (TMAO), tetramethylarsonium (Tetra), arsenocholine
      (AsC) and arsenobetaine (AsB) is between 0.04 and 0.07 ng/mL, with a linear range
      of 0.2 - 500 ng/mL. Three unknown arsenic species (Unk1, Unk2 and Unk3) and six
      specific arsenic species (AsIII, AsV, DMA, TMAO, Tetra and AsB) were detected in
      the extract of tree moss. Unk3 was identified as a kind of arsenosugars (2,3
      dihydroxypropyl-5-deoxy-5(dimethylarsenoso)furanoside, arsenosugar X) by
      electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-qTOF
      MS).

PMID- 29567189
TI  - Fast blood plasma separation device for point-of-care applications.
AB  - In this work, a simple device for extremely fast separation of blood plasma from
      diluted whole blood was developed. The device accommodates an asymmetric
      polysulfone membrane/supporting membrane sandwich that allows collection of 10 uL
      blood plasma into a narrow glass capillary in less than 10 s. The composition of
      diluent solution was optimized in order to achieve maximum recoveries for
      selected metabolites of alcohol intoxication. 5% solution of
      [tris(hydroxymethyl)methylamino] propanesulfonic acid provided recoveries of
      formate, oxalate and glycolate close to 100% and only moderate erythrocyte lysis.
      Both charged and uncharged compounds from the whole blood samples can be analyzed
      in the separated blood plasma by capillary electrophoresis with contactless
      conductometric detection and spectrophotometry, respectively. The developed
      device might find wide application in on-site testing and point-of-care analysis,
      when only microliter volumes of whole blood are available.

PMID- 29567190
TI  - Nitrogen and phosphorus dual-doped carbon dots as a label-free sensor for
      Curcumin determination in real sample and cellular imaging.
AB  - A nitrogen and phosphorus dual-doped carbon dots (NP-Cdots) was fastly
      synthesized with glucose as the carbon source, 1,2-ethylenediamine as N-dopant
      and concentrated phosphoric acid as P-dopant. The as-synthesized NP-Cdots was
      utilized as a label-free sensor for determination of Curcumin (Cur). The proposed
      NP-Cdots-based fluorescence sensor was applied for sensitive detection of Cur in
      aqueous solution, achieving a linear range of 0.5-20 umol/L and a detection limit
      of 58 nmol/L (21.37 ng/mL). The common amino acids and other drugs do not
      interfere with the detection of Cur, providing good selectivity. The constructed
      sensor was successfully applied to the determination of Cur in drinking water and
      the food samples with satisfactory results and the RSDs and recoveries were 0.08
      5.39% and 95.2-105.2%, respectively. More importantly, the as-prepared NP-Cdots
      was used as effective fluorescent agent for cellular imaging without noticeable
      cytotoxicity. The proposed sensor is simple and practical, illustrating that the
      potential application of NP-Cdots for biosensing, food monitoring and cellular
      labeling and imaging.

PMID- 29567191
TI  - A review of flow analysis methods for determination of radionuclides in nuclear
      wastes and nuclear reactor coolants.
AB  - The safety and security of nuclear power plant operations depend on the
      application of the most appropriate techniques and methods of chemical analysis,
      where modern flow analysis methods prevail. Nevertheless, the current status of
      the development of these methods is more limited than it might be expected based
      on their genuine advantages. The main aim of this paper is to review the
      automated flow analysis procedures developed with various detection methods for
      the nuclear energy industry. The flow analysis methods for the determination of
      radionuclides, that have been reported to date, are primarily focused on their
      environmental applications. The benefits of the application of flow methods in
      both monitoring of the nuclear wastes and process analysis of the primary circuit
      coolants of light water nuclear reactors will also be discussed. The application
      of either continuous flow methods (CFA) or injection methods (FIA, SIA) of the
      flow analysis with the beta-radiometric detection shortens the analysis time and
      improves the precision of determination due to mechanization of certain time
      consuming operations of the sample processing. Compared to the radiometric
      detection, the mass spectrometry (MS) detection enables one to perform
      multicomponent analyses as well as the determination of transuranic isotopes with
      much better limits of detection.

PMID- 29567192
TI  - MOF based fluorescent assay of xanthine oxidase for rapid inhibitor screening
      with real-time kinetics monitoring.
AB  - The activity assay of xanthine oxidase (XO) is of great application value in
      clinical diagnosis because the abnormal level of this enzyme is related to a
      series of pathological states. In this work, a Zr based metal-organic framework
      (BTB-MOF) with stable photoluminescence in pure water and buffer solution was
      synthesized. The examination about the fluorescent responses of this material to
      xanthine and its oxidation product, uric acid, showed that, although both of them
      affected the emission of BTB-MOF in quenching form, the efficiencies presented
      much difference. Taking advantage of this feature, a fluorescent method was
      developed for the activity assay of XO, that is, BTB-MOF was added to the
      enzymatic oxidation system as a sensor to transduce the proceeding of the
      reaction real-timely to the signal of fluorescent intensity change. Our method
      can work under the interference of normal biologically related species, and
      precisely reflect XO activity in the range of 0.2-40 U L-1 (detection limit =
      0.004 U L-1). With consecutive fluorescence intensity scan, this assay could be
      applied as a high speed screening method of XO inhibitors with the testing time
      of 1 min. This work shows the wide potential application of MOFs in enzyme
      analysis.

PMID- 29567193
TI  - Tube radial distribution chromatography system developed by combining
      commercially available HPLC system and open-tubular capillary tube as separation
      column.
AB  - Tube radial distribution chromatography based on tube radial distribution flow,
      or annular flow, in an open-tubular capillary has been reported, where the
      annular flow is created through phase separation multiphase flow. The
      chromatographic system requires some specific instruments and treatments for
      microfluidic flow in the capillary tube. In this study, we developed a new set-up
      for tube radial distribution chromatography by combining a commercially available
      HPLC system with an open-tubular capillary tube (with an inner diameter of 100
      um) as a separation column instead of a conventional packed column. The analyte
      solution was injected with an injection valve (2 MUL volume) and a ternary
      solution of water/acetonitrile/ethyl acetate (3:8:2 vol ratio) was delivered as
      the eluent to the capillary tube at a flow rate of 8.6 MUL min-1. The
      chromatographic system, that is, the HPLC system equipped with the open-tubular
      capillary tube, could successfully separate the model analytes, 1-naphthol, 1
      naphthalenesulfonic acid, and 2,6-naphthalenedisulfonic acid, with base-line
      separation. The inner and outer phases in the annular flow worked as the mobile
      and pseudo-stationary phases, respectively, in the tube radial distribution
      chromatography system. The experimentally obtained elution times of the analytes
      were compared with their corresponding theoretical values calculated using their
      capacity factors for the inner and outer phases and the linear flow velocities of
      the respective phases.

PMID- 29567194
TI  - A fast and simple air-assisted liquid-liquid microextraction procedure for the
      simultaneous determination of bisphenols, parabens, benzophenones, triclosan, and
      triclocarban in human urine by liquid chromatography-tandem mass spectrometry.
AB  - The increasing awareness and public concern with hazard exposure to endocrine
      disrupting chemicals calls for methods capable to handle numerous samples in
      short analysis time. In this present study, a novel method combining air-assisted
      liquid-liquid microextraction and liquid chromatography coupled to mass
      spectrometry was developed and validated for the extraction, preconcentration,
      and determination of 7 bisphenols (bisphenol A, bisphenol S, bisphenol AP,
      bisphenol P, bisphenol F, bisphenol AF, bisphenol Z), 7 parabens (methyl-, ethyl
      , propyl-, butyl-, benzyl-paraben, methyl-protocatechuic acid, and ethyl
      protocatechuic acid), 5 benzophenones (benzophenone-1, benzophenone-2,
      benzophenone-3, benzophenone-8, and 4-hydroxybenzophenone), and two
      antimicrobials (triclosan and triclocarban) in human urine samples. Type and
      volume of solvent, extraction time (cycles), pH sample, ionic strength,
      agitation, and needle dimensions were evaluated. The matrix-matched calibration
      curves of all analytes were linear with correlation coefficients higher than 0.99
      in the range level of 1.0-20.0 ng mL-1. The relative standard deviation,
      precision, at three concentrations (1.0, 10.0 and 20.0 ng mL-1) was lower than
      15% with accuracy ranging from 90% to 114%. The biomonitoring capability of the
      new proposed method was confirmed with the analysis of 50 human urine samples
      randomly collected from Brazilian children. High urinary concentrations of
      several EDCs associated with usage of personal care products were found.

PMID- 29567195
TI  - Modeling the effects of material properties on tablet compaction: A building
      block for controlling both batch and continuous pharmaceutical manufacturing
      processes.
AB  - As the pharmaceutical industry modernizes its manufacturing practices and
      incorporates more efficient processing approaches, it is important to reevaluate
      which process design elements affect product quality and the means to study these
      systems. The purpose of this work is to provide insight on a methodology to
      correlate the effect of raw material properties to equipment and process
      performance using both data-driven and semi-empirical models. In this work,
      lubricated blends of pharmaceutically-relevant materials were made using varying
      levels of magnesium stearate, ranging from 0.25 to 1.5%. Materials
      characterization (e.g., compressibility, permeability, density, particle size)
      was performed for all materials and blends. The blends were compressed using a
      two by three experimental design, varying tablet fill cam depth and tablet
      thickness, respectively. Tablet properties (e.g., weight, tensile strength, and
      thickness) were collected for all tablets. Using the collected tablet property
      results, models coefficients for the semi-empirical Kuentz and Leuenberger
      equation, which relates the tablet tensile strength to changes in porosity, were
      regressed. Empirical models were then developed to correlate the values of the
      Kuentz and Leuenberger equation coefficients to the blend material properties.
      The empirical models were then used in conjunction with the Kuentz and
      Leuenberger equation to evaluate the compression design and operational space,
      accounting for material properties. This proof of concept work aimed at
      developing correlations between raw material properties and unit operation models
      can aid process development, especially in design space characterization and
      robustness analysis.

PMID- 29567196
TI  - Comparison of melibiose and trehalose as stabilising excipients for spray-dried
      beta-galactosidase formulations.
AB  - Spray-dried protein formulations commonly require stabilising excipients to
      prevent protein degradation during processing and storage, and trehalose has been
      commonly used. The purpose of this work was to evaluate melibiose in spray-dried
      protein formulations in comparison to trehalose. The protein-activity-preserving
      efficacy, process behaviour and storage stability were studied. Spray drying of
      beta-galactosidase was carried out using different process temperature, drying
      air flow and feed liquid atomisation settings. Both melibiose and trehalose
      reduced protein activity loss during drying. A decrease in activities was
      observed when the process temperature exceeded a threshold temperature. During
      storage (30 days at 18% RH and 20 or 40  degrees C), the formulations dried below
      this threshold temperature showed no further activity loss, and the stabilising
      efficacy of the two disaccharides was equal. With higher process temperatures,
      the remaining protein activities after storage trended higher with melibiose
      formulations. All formulations remained amorphous. The powder yields of melibiose
      formulations were similar to trehalose. There was a difference in residual
      moisture contents, with melibiose formulations giving drier products. In
      conclusion, protein formulations with melibiose could be spray dried into
      amorphous powders that were physically stable, contained lower moisture contents
      and protected protein activity at least as well as trehalose formulations.

PMID- 29567197
TI  - Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic
      alginate composite thermogel.
AB  - As the life expectancy of the world population increases, osteoporotic (OP)
      fracture risk increase. Therefore in the present study a novel injectable thermo
      responsive hydrogel loaded with microspheres of 17beta-estradiol, microspheres of
      bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was
      applied locally to regenerate a calvaria critical bone defect in OP female rats.
      Three systems were characterized: Tetronic(r) 1307 (T-1307) reinforced with
      alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the
      microspheres increased the viscosity but the temperature for the maximum
      viscosity did not change (22-24  degrees C). The drugs were released during 6
      weeks in one fast phase (three days) followed by a long slow phase. In vivo
      evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres
      of 17beta-estradiol (T-A-betaE), T-A-betaE prepared with PRGF (T-A-PRGF-betaE), T
      A-betaE with microspheres of BMP-2 (T-A-betaE-BMP-2) and the combination of the
      three (T-A-PRGF-betaE-BMP). After 12 weeks, histological and histomorphometric
      analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-betaE
      formulation. The PRGF did not increased the bone repair. The new bone filling the
      OP defect was less mineralized than in the non-OP groups.

PMID- 29567198
TI  - Lipid bilayer-coated mesoporous silica nanoparticles carrying bovine hemoglobin
      towards an erythrocyte mimic.
AB  - Hemoglobin (Hb)-loaded mesoporous silica nanoparticles (MSNs) coated with a lipid
      bilayer (LB-MSNs) were investigated as an erythrocyte mimic. MSNs with a large
      average pore size (10 nm) act as a rigid core and provide a protective
      environment for Hb encapsulated inside the pores. The colloidal stability of Hb
      loaded MSNs was enhanced upon the application of a lipid bilayer, through fusion
      of PEGylated liposomes onto the exterior surface of Hb-loaded MSNs. The
      morphology and mesostructure of the MSNs were characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM) and surface area
      analysis. The Hb loading capacity (mg/g) in MSNs was studied by thermogravimetric
      analysis (TGA). UV-Vis absorption spectroscopy revealed that Hb inside MSNs had
      an identical, but slightly broadened peak in the Soret region compared to free
      Hb. Furthermore the encapsulated Hb exhibits similar peroxidase-like activity in
      catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic
      acid) diammonium salt (ABTS) with hydrogen peroxide. The introduction of a
      supported lipid bilayer (LB) demonstrated the potential to prevent premature Hb
      release (the burst release decreased from 25.50 +/- 0.33% to 6.73 +/- 0.83%) and
      increased the colloidal stability of the Hb-loaded MSNs (hydrodynamic diameter
      remained ~250 nm for at least one week). The in vivo systemic circulation and
      biodistribution of LB-MSNs were studied in optically transparent zebrafish
      embryos, revealing that LB-MSNs have the potential to act as an erythrocyte mimic
      in transfusion therapy.

PMID- 29567199
TI  - Are surgeons overdosing patients with lidocaine?

PMID- 29567200
TI  - The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of
      bone-sustaining bisphosphonates that regulates osteogenic differentiation and
      mineralization.
AB  - Bisphosphonates play an important role in the treatment of metabolic bone
      diseases such as osteoporosis. In addition to their anti-resorptive activity by
      triggering osteoclast apoptosis, nitrogen-containing bisphosphonates (N-BP) may
      also influence osteogenic differentiation, which might rely on their capacity to
      inhibit the mevalonate pathway. In vascular endothelial cells inhibition of this
      pathway by cholesterol-lowering statins activates the MEK5/ERK5 mitogen-activated
      protein kinase cascade, which plays an important role in cellular
      differentiation, apoptosis or inflammatory processes. Here we evaluated whether N
      BP may also target the MEK5/ERK5 pathway and analysed the consequences of ERK5
      activation on osteogenic differentiation. We show that N-BP dose-dependently
      activate ERK5 in primary human endothelial cells and osteoblasts. The mechanism
      likely involves farnesyl pyrophosphate synthase inhibition and subsequent
      functional inhibition of the small GTPase Cdc42 since siRNA-mediated knockdown of
      both genes could reproduce N-BP-induced ERK5 activation. ERK5 activation resulted
      in regulation of several bone-relevant genes and was required for calcification
      and osteogenic differentiation of bone marrow-derived mesenchymal stems cells as
      evident by the lack of alkaline phosphatase induction and alizarin-red S staining
      observed upon ERK5 knockdown or upon differentiation initiation in presence of a
      pharmacological ERK5 inhibitor. Our data provide evidence that N-BP activate the
      MEK5/ERK5 cascade and reveal an essential role of ERK5 in osteogenic
      differentiation and mineralization of skeletal precursors.

PMID- 29567201
TI  - In utero heat stress causes reduced testicular area at puberty, reduced total
      sperm production, and increased sperm abnormalities in boars.
AB  - In utero stress has been shown to negatively affect intact male rats and mice,
      though very little research has been conducted in boars. The objectives of the
      present studies were to determine the effects of in utero heat stress (IUHS) on
      postnatal development and the response to postnatal heat stress of boars. Ten
      boars were selected at weaning from litters subjected to IUHS or in utero
      thermoneutral (IUTN) during 30-60 days of gestation. The boars were evaluated for
      reproductive performance from birth through 57 weeks of age (WOA). Testicular
      area tended to be smaller for IUHS boars compared to IUTN boars at 24 WOA (P =
      0.080). Libido did not differ for IUHS or IUTN (P = 0.818). Total sperm
      production was reduced in IUHS boars compared to IUTN boars (P <= 0.038). Semen
      volume and semen concentration did not differ (P >= 0.469 and P >= 0.664,
      respectively). Total motility and progressive motility did not differ for IUHS
      and IUTN boars (P >= 0.430 and P >= 0.652, respectively). In utero heat stressed
      boars had a greater incidence of sperm with tail abnormalities than IUTN (P <=
      0.042). In utero heat stressed boars had a lower incidence of sperm with proximal
      droplets following mild, postnatal heat stress compared with IUTN (P = 0.005). In
      utero heat stress resulted in significant reductions in sperm production and
      increased sperm abnormalities in boars. The IUHS boars may be slightly more
      tolerant to postnatal heat stress, though more research is needed.

PMID- 29567202
TI  - Mating induces production of MMP2 in the llama oviduct: Analysis of MMP2 effect
      on semen.
AB  - Ovulation of South American Camelids is induced by mating. After copulation,
      sperm are stored into the oviduct to be released near ovulation time. To study
      whether copulation induces matrix metalloproteinase-2 (MMP2) secretion in the
      oviduct, the occurrence of MMP2 in oviductal tissue and oviductal fluid (OF) from
      24 h post-mated was compared with non-mated llama females. There was an
      incremental increase of MMP2 in the oviductal epithelial cells, and MMP2 activity
      in OF after copulation. Additionally, MMP2 activator (MMP14), inducer (EMMPRIN)
      and inhibitor (TIMP2) were present in the oviductal epithelial cells of both non
      mated and post-mated females. A post-mating segment-specific regulation occurred
      because relative abundance of TIMP2 mRNA was greater in the utero tubal-junction
      which was accompanied with a reduced amount of MMP14 in the ampulla in comparison
      with the non-mated females. To examine the effect of MMP2 on semen liquefaction
      and sperm physiology, the effects of addition of recombinant human MMP2 was
      evaluated. The MMP2 had no effect on semen thread formation and seminal plasma
      protein profile. Sperm viability and plasma membrane function were not influenced
      by the enzyme treatment either. In summary, in llamas the oviductal
      microenvironment changes in response to stimuli induced by copulation, increasing
      the production and secretion of MMP2.

PMID- 29567203
TI  - Assessment of reproductive performance in F1 sows exposed to the porcine epidemic
      diarrhea virus at different periods of production stage on farms with different
      hygienic environments.
AB  - Porcine epidemic diarrhea (PED) occurred in Japan in 2013 after an interval of 7
      years. The present study assessed individual productivity of sows exposed to PED
      virus at different periods of the production stage. The present study was
      performed at three commercial farms that had PED outbreak during the month of
      December 2013. Herd immunization was conducted for all gilts and sows. The
      production records were obtained for sows that were alive during the PED outbreak
      at each farm. The sows were categorized into six groups based on the period in
      which they were exposed to PED virus between days 0-30 (G1), 31-60 (G2), 61-90
      (G3), or after 91 days of pregnancy (G4), during lactation (L), and after weaning
      (W). The control group was assigned based on the records before the period of PED
      outbreak (uninfected group). The number of sow's records obtained from farms A,
      B, and C were 1056, 1137, and 1035, respectively. Compared with the uninfected
      group, there was no reduction in the number of pigs born alive in the G1-G4
      groups. Sows of the G4 and L groups, however, had 4-9 pigs fewer pigs weaned, and
      a 36%-77% greater pre-weaning mortality than the uninfected group (P < 0.05).
      There was no difference in farrowing rate and number of pigs born alive at
      subsequent parities among the sow groups. There were no interactions between sow
      groups and parity for sow productivity.

PMID- 29567204
TI  - Experts' perspectives on SwissDRG: Second class care for vulnerable patient
      groups?
AB  - On the 1st of January 2012, Switzerland introduced the diagnosis-related group
      hospital tariff structure (SwissDRG). It was recognised that healthcare provided
      to the most vulnerable patient groups would be a challenge for the new SwissDRG.
      Coincident with the implementation of SwissDRG, we explored hospital experts'
      perceptions of which patient groups are vulnerable under the SwissDRG system,
      what has changed for this group, as well as solutions to ensure adequate access
      to health care for them. We interviewed 43 experts from 40 Swiss hospitals.
      Participating experts named several vulnerable patient groups who share some
      common characteristics. These hospital experts were concerned about the patient
      groups that are not financially profitable and questioned the practicability of
      the current regulation. At the same time, they highlighted the complexity
      associated with caring for this group under the new SwissDRG and reported
      measures at the macro, meso, and micro levels to protect vulnerable patient
      groups from negative effects. To curb negative outcomes for vulnerable patient
      groups after the introduction of the SwissDRG, the Swiss legislation has
      introduced various instruments including the acute and transitional care (ATC)
      measures. We conclude that ATC measures do not produce the expected effect the
      legislators had hoped for. More health data is needed to identify situations
      where vulnerable patient groups are more susceptible to inadequate health care
      access in Switzerland.

PMID- 29567205
TI  - Innovative pharmaceutical pricing agreements in five European markets: A survey
      of stakeholder attitudes and experience.
AB  - BACKGROUND: Innovative pricing agreements for medicines have been used in
      European markets for more than 20 years, and offer an opportunity for payers and
      pharmaceutical companies to align on value, optimise speed to patients, and share
      risk. Developing successful agreements requires alignment between key
      stakeholders, yet there is a lack of summative data on how current innovative
      agreements are used in the real-world (e.g. the level of realised access to
      medicines, and rebates and discounts, which are often non-transparent). METHODS:
      This research used a web-based survey of payer stakeholders to determine what
      kinds of innovative agreements are currently used, anticipated future usage,
      attitudes, and drivers of adoption. Participants included national and regional
      payers (or former payers) and hospital-level decision makers. RESULTS: Sixty-six
      payers completed the survey. Respondents expected that the use of innovative
      pricing agreements will remain the same or increase in the future. Overall, they
      felt there is a positive attitude towards new schemes, and that innovative
      agreements are likely to be used when they reduce total costs or reduce
      uncertainty. CONCLUSIONS: Given payer expectations, pharmaceutical companies
      should continue to take a role in ensuring that they have sufficient capacity to
      support payers in the design and implementation of innovative pricing agreements.

PMID- 29567206
TI  - Editorial Comment.

PMID- 29567207
TI  - Reply.

PMID- 29567208
TI  - Deciphering protein dynamics changes along the pathway of retinol uptake by
      cellular retinol-binding proteins 1 and 2.
AB  - Four Cellular Retinol-binding Proteins (CRBP 1, 2, 3, 4) are encoded in the human
      genome. CRBP 1 and 2, sharing a 56% amino acid sequence identity, exhibit the
      highest binding affinities for retinol. Previous NMR studies provided some
      insights into the mechanism of retinol uptake, but details of such mechanism
      remain to be elucidated. Herein, the results of molecular dynamics simulations
      for the uptake of retinol by CRBP 1 and 2 are consistent with the presence of two
      different retinol entry points, both involving the 'cap region' (alpha-helices I
      and II and neighboring loops). We observed that a hydrophobic patch at the
      surface of the 'portal region' (alpha-helix II, CD and EF loops) of CRBP 1
      attracts retinol, which accesses the binding cavity through an opening generated
      by the concerted movements of Arg58 and Phe57, present in the CD loop. In CRBP 2
      a different distribution of the surface residues of the 'cap region' allows
      retinol to access the binding cavity by sinking in a hydrophobic matrix between
      the two alpha-helices. Polar interactions mainly affect retinol movements inside
      the beta-barrel cavities of both CRBPs. The interaction energy profiles are in
      agreement with the different behavior of the two protein systems.

PMID- 29567209
TI  - Heterotopic Ossification: The Keys to the Kingdom.

PMID- 29567211
TI  - Cardiac Toxicity in Patients Treated With Immune Checkpoint Inhibitors: It Is Now
      Time for Cardio-Immuno-Oncology.

PMID- 29567210
TI  - Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
AB  - BACKGROUND: Myocarditis is an uncommon, but potentially fatal, toxicity of immune
      checkpoint inhibitors (ICI). Myocarditis after ICI has not been well
      characterized. OBJECTIVES: The authors sought to understand the presentation and
      clinical course of ICI-associated myocarditis. METHODS: After observation of
      sporadic ICI-associated myocarditis cases, the authors created a multicenter
      registry with 8 sites. From November 2013 to July 2017, there were 35 patients
      with ICI-associated myocarditis, who were compared to a random sample of 105 ICI
      treated patients without myocarditis. Covariates of interest were extracted from
      medical records including the occurrence of major adverse cardiac events (MACE),
      defined as the composite of cardiovascular death, cardiogenic shock, cardiac
      arrest, and hemodynamically significant complete heart block. RESULTS: The
      prevalence of myocarditis was 1.14% with a median time of onset of 34 days after
      starting ICI (interquartile range: 21 to 75 days). Cases were 65 +/- 13 years of
      age, 29% were female, and 54% had no other immune-related side effects. Relative
      to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p
      = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214
      days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with
      normal ejection fraction. There was a 4-fold increased risk of MACE with troponin
      T of >=1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p =
      0.003). Steroids were administered in 89%, and lower steroids doses were
      associated with higher residual troponin and higher MACE rates. CONCLUSIONS:
      Myocarditis after ICI therapy may be more common than appreciated, occurs early
      after starting treatment, has a malignant course, and responds to higher steroid
      doses.

PMID- 29567212
TI  - Molecular dissection of the membrane aggregation mechanisms induced by monomeric
      annexin A2.
AB  - Annexins are a multigene family of proteins involved in aggregation and fusion
      processes of biological membranes. One of its best-known members is annexin A2
      (or p36), capable of binding to acidic phospholipids in a calcium-dependent
      manner, as occurs with other members of the same family. In its heterotetrameric
      form, especially with protein S100A10 (p11), annexin A2 has been involved as a
      determinant factor in innumerable biological processes like tumor development or
      anticoagulation. However, the subcellular coexistence of different pools of the
      protein, in which the monomeric form of annexin A2 is growing in functional
      relevance, is to date poorly described. In this work we present an exhaustive
      structural and functional characterization of monomeric human annexin A2 by using
      different recombinant mutants. The important role of the amphipathic N-terminal
      alpha-helix in membrane binding and aggregation has been analyzed. We have also
      studied the potential implication of lateral "antiparallel" protein dimers in
      membrane aggregation. In contrast to what was previously suggested, formation of
      these dimers negatively regulate aggregation. We have also confirmed the
      essential role of three lysine residues located in the convex surface of the
      molecule in calcium-free and calcium-dependent membrane binding and aggregation.
      Finally, we propose models for annexin A2-mediated vesicle aggregation
      mechanisms.

PMID- 29567214
TI  - Volatile sulfur compounds in tropical fruits.
AB  - Global production and demand for tropical fruits continues to grow each year as
      consumers are enticed by the exotic flavors and potential health benefits that
      these fruits possess. Volatile sulfur compounds (VSCs) are often responsible for
      the juicy, fresh aroma of tropical fruits. This poses a challenge for analytical
      chemists to identify these compounds as most often VSCs are found at low
      concentrations in most tropical fruits. The aim of this review is to discuss the
      extraction methods, enrichment techniques, and instrumentation utilized to
      identify and quantify VSCs in natural products. This will be followed by a
      discussion of the VSCs reported in tropical and subtropical fruits, with
      particular attention to the odor and taste attributes of each compound. Finally,
      the biogenesis and enzymatic formation of specific VSCs in tropical fruits will
      be highlighted along with the contribution each possesses to the aroma of their
      respective fruit.

PMID- 29567213
TI  - Contribution of the exosome-associated form of secreted endoplasmic reticulum
      aminopeptidase 1 to exosome-mediated macrophage activation.
AB  - Macrophages secrete endoplasmic reticulum aminopeptidase 1 (ERAP1) in response to
      lipopolysaccharide (LPS) and interferon (IFN)-gamma to enhance their phagocytic
      and nitric oxide (NO) synthetic activities. In this study, we found that a subset
      of secreted ERAP1 bound to exosomes released from LPS/IFN-gamma-treated murine
      RAW264.7 macrophages compared to untreated cells. ERAP1-bound exosomes enhanced
      phagocytic and NO synthetic activities of macrophages more efficiently than free
      ERAP1 and exosomes derived from untreated cells. Deletion of the exon 10 coding
      sequence in ERAP1 gene resulted in loss of binding to exosomes. By comparing the
      activities of exosomes derived from wild-type and ERAP1 gene-deficient RAW264.7
      cells, we observed that ERAP1 contributed to the exosome-dependent phagocytosis
      and NO synthesis of the cells. Upon stimulation of RAW264.7 cells with LPS/IFN
      gamma, TNF-alpha, IFN-gamma, and CCL3 were also associated with the released
      exosomes. Analyses of cytokine function revealed that while CCL3 in the exosomes
      was crucial to the phagocytic activity of RAW264.7 cells, TNF-alpha and IFN-gamma
      primarily contributed to the enhancement of NO synthesis. These results suggest
      that treatment with LPS/IFN-gamma alters the physicochemical properties of
      exosomes released from macrophages in order to facilitate association with ERAP1
      and several cytokines/chemokines. This leads to exosome-mediated enhancement of
      macrophage functions. It is possible that packaging effector molecules into
      exosomes upon inflammatory stimuli, facilitates the exertion of effective
      pathophysiological functions on macrophages. Our data provide the first evidence
      that ERAP1 associated with exosomes plays important roles in inflammatory
      processes via activation of macrophages.

PMID- 29567215
TI  - Standards and labeling of milk fat and spread products in different countries.
AB  - In the present paper, we provide comprehensive information related to labeling
      claims and standards of identity of milk fat and spread products. By reviewing
      the standards and regulations for dairy and non-dairy fat products, Codex
      Alimentarius and several other countries have clearly specified these products
      and set the requirements for use of the product name to prevent misleading or
      confusing the consumers. Generally, for the milkfat products, the fat in the
      products should be exclusively from milk and/or the products obtained from milk.
      The milkfat contents of these products should be no less than 10%. Whereas, the
      blends or blended spreads are mixture of butter and vegetable oils with more than
      3% of milkfat of the total fat content. The fat spreads are defined that any
      milkfat content must be no more than 3% of the total fat content. Although the
      specification of each fat product might be different, most countries still adopt
      the labeling system of Codex Alimentarius, including the use of the food names
      and the "reduced fat" claims. Each of the ingredients used in the food also need
      to be declared on the label.

PMID- 29567216
TI  - Regulatory analysis on the medical use of ephedrine-related products in Taiwan.
AB  - To prevent ephedrine-related products from being misused to produce amphetamine
      and/or its analogs, there's a need for more effective and achievable regulatory
      mechanisms for the health, police, investigational, prosecution and judiciary
      authorities in Taiwan. This review was conducted to evaluate the international
      and Taiwan's regulatory policies and management of medical ephedrine-related
      products through the corresponding information collected from international and
      Taiwan government agency authorities. The combat of illegal drugs should involve
      both supply and demand sides to be successful. Health authorities in Taiwan do
      not have the investigational power to manage the forbidden transformation,
      abusing and manufacture of the illegal drugs from ephedrine-related products.
      Take the judicial interventions in the United States and in Japan as the
      examples, the organizational cooperation in Taiwan can be one of the main key
      strategies to combat against illegal drugs from ephedrine-related products. It is
      necessary to integrate the judicial, police and health agencies to prevent the
      production of illegal drugs from the ephedrine-related products in Taiwan. The
      efforts and regulatory control measures should be integrated to speed up the
      collaboration between different government authorities. It might be achieved
      through reorganization involving Taiwan Food and Drug Administration.

PMID- 29567217
TI  - Bioactive polyphenols in kinkeliba tea (Combretum micranthum) and their glucose
      lowering activities.
AB  - Herbal tea kinkeliba prepared from the leaves of Combretum micranthum has been
      widely consumed in West African countries for its flavor, nutritional and
      medicinal properties. Under bio-guided screening, the kinkeliba leaves were
      chemically investigated using various chromatographic and spectrometric methods
      that led to the identification of thirteen different flavonoid compounds. Further
      biological tests illustrated that the identified compounds may have synergistic
      effects to decrease the expression of phosphoenolpyruvate carboxykinase (PEPCK)
      mRNA and glucose production in an H4IIE hepatoma cell line, indicating its
      potential use for insulin-resistant diabetes treatment. Further in vivo study on
      C57BL/6J mice indicates that kinkeliba can lower plasma glucose levels in a dose
      dependent manner without significant weight loss and toxicity. The ethyl acetate
      extract in rich of flavonoids could also increase the glucose tolerance (GT)
      after seven weeks' administrations. Both in vitro and in vivo experiments support
      a potential new application of kinkeliba leaves as an anti-diabetes agent.

PMID- 29567218
TI  - Characterization of key aroma-active compounds in lychee (Litchi chinensis
      Sonn.).
AB  - Volatile compounds in 'Sweetheart' lychee were examined using gas chromatography
      olfactometry/mass spectrometry (GC-O/MS). Solvent assisted flavor evaporation
      (SAFE) technique was used to identify the aroma-active compounds in lychee.
      Further characterization of the most important odorants in 'Sweetheart' lychee
      was achieved using aroma extract dilution analysis (AEDA). Thirty-one key aroma
      active odorants were identified in the flavor dilution (FD) factor range of 2
      1024. Methional (cooked potato) and geraniol (sweet, floral) exhibited the
      highest FD factors of 1024 and 512, respectively, these were followed by furaneol
      (sweet, caramel), nerol (floral, sweet), dimethyl trisulfide (DMTS) (preserved
      vegetable, sulfury), linalool (floral), (E,Z)-2,6 nonadienal (cucumber) and
      nerolidol (metalic, sesame oil). Furthermore, the flavor profile of 'Sweetheart'
      lychee was described by sensory analysis. Floral, tropical fruit, peach/apricot
      and honey were scored with relatively high scores for each aroma attribute. The
      sweetness rating was the highest score among all the attributes.

PMID- 29567219
TI  - A simple and robust quantitative analysis of retinol and retinyl palmitate using
      a liquid chromatographic isocratic method.
AB  - Vitamin A is a vital nutritional substances that regulates biological activities
      including development, but is also associated with disease onset. The extent of
      vitamin A intake influences the retinoid content in the liver, the most important
      organ for the storage of vitamin A. Measurement of endogenous retinoid in
      biological samples is important to understand retinoid homeostasis. Here we
      present a reliable, highly sensitive, and robust method for the quantification of
      retinol and retinyl palmitate using a reverse-phase HPLC/UV isocratic method. We
      determined the impact of chronic dietary vitamin A on retinoid levels in livers
      of mice fed an AIN-93G semi-purified diet (4 IU/g) compared with an excess
      vitamin A diet (1000 IU/g) over a period from birth to 10 weeks of age.
      Coefficients of variation for intra-assays for both retinoids were less than 5%,
      suggesting a higher reproducibility than any other HPLC/UV gradient method.
      Limits of detection and quantification for retinol were 0.08 pmol, and 0.27 pmol,
      respectively, which are remarkably higher than previous results. Supplementation
      with higher doses of vitamin A over the study period significantly increased
      liver retinol and retinyl palmitate concentrations in adult mice. The assays
      described here provide a sensitive and rigorous quantification of endogenous
      retinol and retinyl palmitate, which can be used to help determine retinoid
      homeostasis in disease states, such as toxic hepatitis and liver cancer.

PMID- 29567220
TI  - Effects of electrode gap and electric current on chlorine generation of
      electrolyzed deep ocean water.
AB  - Electrolyzed water is a sustainable disinfectant, which can comply with food
      safety regulations and is environmental friendly. A two-factor central composite
      design was adopted for studying the effects of electrode gap and electric current
      on chlorine generation efficiency of electrolyzed deep ocean water. Deep ocean
      water was electrolyzed in a glass electrolyzing cell equipped with platinum
      plated titanium anode and cathode in a constant-current operation mode. Results
      showed that current density, chlorine concentration, and electrolyte temperature
      increased with electric current, while electric efficiency decreased with
      electric current and electrode gap. An electrode gap of less than 11.7 mm, and a
      low electric current appeared to be a more energy efficient design and operation
      condition for the electrolysis system.

PMID- 29567221
TI  - Systematic study on active compounds as antibacterial and antibiofilm agent in
      aging onions.
AB  - Quantitative investigation and systematic studies of quercetin, total phenolics,
      flavonoids, antioxidants, antibacterial and antibiofilm or antibiofouling
      properties of methanolic extracts of onions obtained from six different varieties
      have been carried out to explore their relative merits in terms of biological
      activities of fresh and aging onions. Total phenolic content in the extracts was
      examined spectrophotometrically using Folin-Ciocalteau's phenol reagent and total
      antioxidant activity was studied by FRAP and DPPH methods. In vitro antibacterial
      activity of the extracts was investigated on Gram-negative (Escherichia coli and
      Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus
      cereus) respectively, by using a modified Kirby-Bauer disc diffusion method.
      Antibiofilm activity was tested by crystal violet assay. The best results against
      biofilm formation were observed for the extracts obtained from onions stored for
      three months. The total phenolic and antioxidant content found to be increased
      upon aging in all the six varieties; red skinned onion (Happyhong) showed the
      highest level of total phenolics (5110.07 +/- 196.56 MUg GAEg-1 FW) and total
      flavonoids (2254.00 +/- 154.82 MUg QEg-1 FW) after three months. The results
      showed that in all the varieties, quercetin content as well as biological
      activity increases with aging in the stored onions compared with the fresh ones.

PMID- 29567222
TI  - Thyme essential oils from Spain: Aromatic profile ascertained by GC-MS, and their
      antioxidant, anti-lipoxygenase and antimicrobial activities.
AB  - Six samples of red thyme (Thymus zygis) and two samples of winter thyme (Thymus
      hyemalis) essential oils (EOs) were obtained from plants cultivated in south
      eastern Spain and extracted by steam distillation. Analysis by gas chromatography
      coupled with mass spectrometry detection provided the relative (%) and absolute
      (mM) concentrations. Thymol (30-54%), p-cymene (14-27%) and gamma-terpinene (8
      28%) were the most abundant components of T. zygis EO, while 1,8-Cineole (3-37%),
      p-cymene (1-29%), linalool (8-13%) and thymol (0-19%) were the most abundant
      components in the case of T. hyemalis EO. Enantioselective gas chromatography
      identified (-)-linalool, (-)-borneol and (+)-limonene as the main enantiomers.
      Several methods to evaluate antioxidant capacities were applied to the EOs,
      concluding that their activities were mainly due to thymol and linalool. The
      inhibition of lipoxygenase activity, mainly due to thymol, p-cymene and linalool,
      suggested their possible use as anti-inflammatories. The high antibacterial and
      antifungal activities determined for the EOs means that they can be used as
      natural preservatives. The results support the potential use of Thymus sp. EOs as
      natural food, cosmetic and pharmaceutical ingredients.

PMID- 29567223
TI  - Modifications of Atlantic salmon by-product oil for obtaining different omega-3
      polyunsaturated fatty acids concentrates: An approach to comparative analysis.
AB  - Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) rich 2-monoacylglycerols (2
      MAG), omega-3 polyunsaturated free fatty acids (omega-3 PUFFAs) concentrate, and
      PUFA enriched acylglycerols were prepared from salmon frame bone oil (SFBO) by
      enzymatic alcoholysis, urea complexation, and enzymatic esterification,
      respectively. The yields of 2-MAG, omega-3 PUFFAs concentrate, and PUFA enriched
      acylglycerols were 40.25, 16.52, and 15.65%, respectively. omega-3 PUFFAs
      concentrate and PUFA enriched acylglycerols showed darker red color than SFBO and
      2-MAG due to aggregation of astaxanthin pigment in omega-3 PUFFAs concentrate
      during urea complexation. The viscosity and specific gravity of SFBO and PUFA
      enriched acylglycerols showed similar values whereas 2-MAG and omega-3 PUFFAs
      showed significantly (p < 0.05) lower values. Stability parameters like acid
      value, peroxide value, free fatty acid value, and p-anisidine value of SFBO and
      omega-3 PUFAs concentrates were within acceptable limits except extreme high acid
      value and free fatty acid value of omega-3 PUFFAs concentrate. Thermogravimetric
      analysis showed similar and higher thermal stability of SFBO and PUFA enriched
      acylglycerols than 2-MAG and omega-3 PUFFAs concentrate. The omega-3 PUFAs
      content in 2-MAG, omega-3 PUFFAs concentrate, and PUFA enriched acylglycerols was
      increased to 20.81, 52.96, and 51.74% respectively from 13.54% in SFBO. omega-3
      PUFFAs concentrate and PUFA enriched acylglycerols showed higher DPPH and ABTS
      radical scavenging activity than SFBO and 2-MAG. The results obtained from this
      study suggest the production of PUFA enriched acylglycerols rich in omega-3 PUFAs
      supplements from fish oil for human and pet animals.

PMID- 29567224
TI  - Cytotoxic protobassic acid saponins from the kernels of Palaquium formosanum.
AB  - Bioassay guided fractionation and separation of the EtOH extract of the kernels
      of Palaquium formosanum against PC-3 cells via Sephadex LH-20 and reverse phase C
      18 columns led to the isolation of 13 protobassic saponins. One of these saponins
      is new and was characterized as 3'''-O-rhamnopyranosyl-arganin C, a bisdesmoside
      of 16alpha-hydroxyprotobassic acid at the C-3 and C-28 positions. The structures
      of these compounds were determined on the basis of 1D NMR (1H, 13C), 2D NMR (1H
      1H COSY, HSQC, HMBC, and NOESY), and selectively excited 1D TOCSY spectroscopic
      analyses and MS data, and comparison with literature data. Bioassay of these
      compounds and five additional compounds, isolated from Planchonella obovata leaf,
      against PC-3 prostate cancer cells indicated arganin C to be the most potent one
      with the IC50 value of 13.8 MUM. Some structure and activity relationships were
      also drawn.

PMID- 29567225
TI  - Analysis of veterinary drug residue monitoring results for commercial livestock
      products in Taiwan between 2011 and 2015.
AB  - Antibiotics have been widely used in the treatment of livestock diseases.
      However, the emergence of issues related to drug resistance prompted governments
      to enact a series of laws regulating the use of antibiotics in livestock.
      Following control of the problem of drug resistant bacteria, public attention has
      shifted to the recurring incidence of human health and safety issues caused by
      residual veterinary drugs in livestock products. To guarantee the safety and
      hygiene of meat, milk, and eggs from food-producing animals, governments and
      relevant agencies established laws and regulations for the use of veterinary
      drugs. It is, therefore, necessary to monitor the content of residual drugs in
      livestock products at regular intervals to assess whether the regulations have
      resulted in the effective management of food product safety, and to prevent and
      manage sudden problems related to this issue. A 2011-2015 livestock product post
      marketing monitoring program launched by the Taiwan Food and Drug Administration
      (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34
      samples identified that did not conform to the regulations; these samples
      included residue drugs such as beta-agonists, chloramphenicols, beta-lactam
      antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial
      livestock products with the consistent cooperation of agricultural authorities
      did not detect the drugs that were banned by the government, whereas the
      detection of other drugs decreased annually with an increase in the post-market
      monitoring sample size. In the future, the TFDA will continue to monitor the
      status of residual veterinary drugs in commercial livestock products, adjust the
      sampling of food products annually according to monitoring results, and closely
      cooperate with agricultural authorities on source management.

PMID- 29567226
TI  - Use of UHPLC-TripleQ with synthetic standards to profile anti-inflammatory
      hydroxycinnamic acid amides in root barks and leaves of Lycium barbarum.
AB  - Hydroxycinnamic acid amides (HCAA) are the secondary metabolites ubiquitously
      exist in flowering plants, formed by condensation between hydroxycinnamates and
      mono or polyamines. HCAA species not only serve multiple functions in plant
      growth and development, but also exert significant positive effects on human
      health. In this study, we combined organic synthesis and UPHLC-TripleQ-MS/MS
      specifically targeting at HCAA species. The method was fully validated with
      respect to specificity, linearity, intra- and inter-day precision and accuracy,
      limit of detection (LOD), limit of quantification (LOQ), recovery, and
      reproducibility. We applied this method to identify and quantify HCAAs from the
      root barks and leaves of Lycium barbarum. HCAA species were reported in leaves
      for the first time, and 10 new HCAA species were further identified in root barks
      in addition to the ones reported in the literature. We also examine anti
      inflammatory properties of identified HCAAs species. Seven HCAA compounds had a
      potent NO inhibitory effect with IC50 as low as 2.381 MUM (trans-N-caffeoyl
      phenethylamine). Our developed method largely improved analytical sensitivity of
      HCAAs species that potentially contributes to plant metabolomics studies.

PMID- 29567227
TI  - Employing natural reagents from turmeric and lime for acetic acid determination
      in vinegar sample.
AB  - A simple, rapid and environmentally friendly sequential injection analysis system
      employing natural extract reagents was developed for the determination of acetic
      acid following an acid-base reaction in the presence of an indicator. Powdered
      lime and turmeric were utilized as the natural base and indicator, respectively.
      Mixing lime and turmeric produced an orange to reddish-brown color solution which
      absorbed the maximum wavelength at 455 nm, with absorbance decreasing with
      increasing acetic acid concentration. Influential parameters including lime and
      turmeric concentrations, reagent and sample aspirated volumes, mixing coil length
      and dispensing flow rate were investigated and optimized. A standard calibration
      graph was plotted for 0-5.0 mmol/L acetic acid with r2 = 0.9925. Relative
      standard deviations (RSD) at 2.0 and 4.0 mmol/L acetic acid were less than 3% (n
      = 7), with limit of detection (LOD) and limit of quantification (LOQ) at 0.12 and
      0.24 mmol/L, respectively. The method was successfully applied to assay acetic
      acid concentration in cooking vinegar samples. Results achieved were not
      significantly different from those obtained following a batchwise standard AOAC
      titration method.

PMID- 29567228
TI  - Antioxidant activity and calcium binding of isomeric hydroxybenzoates.
AB  - The association constant for calcium binding to hydroxybenzoates in aqueous 0.16
      M NaCl at 25  degrees C was found electrochemically to have the value Kass = 280
      mol L-1 with DeltaHo = -51 kJ mol-1, DeltaSo = -122 J mol-1 K-1 for the 2-isomer
      (salicylate), Kass = 7 mol L-1 with DeltaHo = -39 kJ mol-1, DeltaSo = -116 J mol
      1 K-1 for the 3-isomer, and Kass = 8 mol L-1 with DeltaHo = -51 kJ mol-1, DeltaSo
      = -155 J mol-1 K-1 for the 4-isomer. The 3- and 4-isomers were found more
      efficient as antioxidants than the 2-isomer in decreasing oxygen consumption rate
      in a peroxidating methyl linoleate emulsion and less sensitive to presence of
      calcium. All isomers were found prooxidative for iron-catalyzed initiation of
      oxidation due to enhanced radical formation as shown by electron spin resonance
      spectroscopy. Calcium salicylate was found to have low solubility with a
      solubility product Ksp = 4.49.10-6 based on activity with DeltaHo = 67 kJ mol-1,
      DeltaSo = 123 J mol-1 K-1 for dissolution in water, when corrected for the strong
      complex formation. Calcium in food and beverages may thus lower antioxidant
      activity of plant phenols through complexation or by precipitation.

PMID- 29567229
TI  - Water-soluble polysaccharides from Ulva intestinalis: Molecular properties,
      structural elucidation and immunomodulatory activities.
AB  - Water-soluble sulfated polysaccharides extracted from Ulva intestinalis and
      fractionated using DEAE Sepharose fast flow column to identify their molecular
      properties and macrophage cells stimulating activities. Crude and fractions (F1
      and F2) were formed of neutral sugars (58.7-74.7%), sulfates (6.2-24.5%), uronic
      acids (4.9-5.9%) and proteins (3.2-10.4%). Different levels of sugar constituents
      including rhamnose (30.1-39.1%), glucose (39.0-48.4%), galactose (0.0-15.8%),
      xylose (8.5-11.3) and arabinose (0.0-5.1%). The molecular weight (Mw) of crude
      and fractionated polysaccharides ranged from 87.1 * 103 to 194.1 * 103 (g/mol).
      Crude polysaccharides were not toxic to RAW264.7 cells and fractions induced cell
      proliferation. Fraction F1 stimulated RAW264.7 cells to release considerable
      amounts of nitric oxide, IL-1beta, TNF-alpha, IL-6, IL-10 and IL-12 cytokines.
      The main backbone of the most immunostimulating polysaccharide (F1) was consisted
      of mixed linkages of (1 -> 2)-linked rhamnose and (1 -> 2)-linked glucose
      residues.

PMID- 29567230
TI  - Relative content of gallic acid over 5-galloylquinic acid as an index for the
      baking intensity of oolong teas.
AB  - Phenolic compounds in a series of old oolong teas prepared by baking annually
      were monitored and compared. The results showed that the relative content of
      gallic acid over 5-galloylquinic acid was subsequently elevated during this
      preparatory process. To reveal the effect was mainly resulted from baking or
      aging, two sets of oolong teas were collected and examined; one set was generated
      from fresh oolong tea via continually daily baking and the other set was composed
      of aged oolong teas with no or light baking in the storage period. The relative
      content of gallic acid over 5-galloylquinic acid was observed to be subsequently
      elevated when oolong tea was continually baked at 90, 100, 110, and 120  degrees
      C for 8 h day after day. In contrast, the relative contents of gallic acid over 5
      galloylquinic acid in aged oolong teas with no or light baking were found to be
      similar to or slightly higher than that in fresh oolong tea. The results suggest
      that the relative content of gallic acid over 5-galloylquinic acid seems to be a
      suitable index for the baking intensity of oolong tea in different preparations.

PMID- 29567231
TI  - Gallic acid inhibits bladder cancer cell proliferation and migration via
      regulating fatty acid synthase (FAS).
AB  - Bladder cancer is known as the world's ninth most prevalent cancer in 2012. New
      cytotoxic drugs have created considerable progress in the treatment. Gallic acid
      (GA) has been shown to inhibit carcinogenesis in animal models and various cancer
      cell lines. The aim of the present study was to evaluate the effect of GA on
      proliferation and migration inhibition of a bladder cancer cell line. The results
      showed that GA inhibited fatty acid synthase (FAS) activity and increased ER
      alpha level of TSGH-8301 bladder cancer cell. GA regulated the cell proliferation
      via the PI3K/AKT and MAPK/ERK pathway. Immunoprecipitation assay demonstrated
      that GA decreased Skp2 protein level and attenuated Skp2-p27 association. It was
      suggested that GA acted upstream of the proteasome to control p27 levels and
      ultimately inhibited G2/M phase transition. Further, transwell chambers assay
      showed that GA suppressed bladder cancer cell invasion and migration through p
      AKT/MMP-2 signaling pathway. The finding indicated that GA inhibited TSGH-8301
      bladder cancer cell growth, invasion and migration through inhibition of fatty
      acid synthase.

PMID- 29567233
TI  - Modified QuEChERS method for 24 plant growth regulators in grapes using LC-MS/MS.
AB  - A multiresidue analytical method was developed for grapes for the following 24
      plant growth regulators: 1-naphthylacetamide, 2,3,5-triiodobenzoic acid, 2,4,5-T,
      2-naphthoxyacetic acid, 3-indolylacetic acid, 4-(3-indolyl)-butyric acid, 4
      chlorophenoxyacetic acid, 4-nitrophenol, 6-benzylaminopurine, N6
      isopentenyladenine, butralin, chlormequat chloride, chlorphonim-Cl, cloprop,
      forchlorfenuron, gibberellic acid 3, gibberellic acid 4, gibberellic acid 7,
      inabenfide, mepiquat chloride, paclobutrazol, prohydrojasmon, thidiazuron and
      uniconizole-P. The compounds were extracted from grape samples using an
      extraction method modified from the Quick, Easy, Cheap, Effective, Rugged and
      Safe (QuEChERS) method. Liquid chromatography - tandem mass spectrometry was used
      for the detection and quantification of the compounds. Validation of the method
      was performed by using recovery studies at both intra-day and inter-day
      intervals, as well as by evaluation of the matrix effect, limit of
      quantification, trueness and precision. We used matrix-matched calibrations for
      the quantification of the compounds, which all resulted in determination
      coefficients (r2) higher than 0.995. The limit of quantification ranged from 0.1
      to 5 ng/mL. Recovery studies using three spiking concentrations at varying levels
      showed recoveries of 70.2-112.6% and 67.5-101.8% at intra-day and inter-day
      intervals, respectively. Relative standard deviations were below 20% for the
      recovery studies. The extraction method were further validated by performing
      recovery study and matrix effect test in six different grape varieties from
      Taiwan and the United States and all resulted in comparable results. Application
      of the established method to 50 grape samples, resulted in the detection of
      chlormequat chloride and forchlorfenuron residues in the tested grapes. The
      results of the method validation and real sample analysis shows the extraction
      method is therefore suitable for routine monitoring of residue in grapes.

PMID- 29567232
TI  - Methodology for sample preparation and size measurement of commercial ZnO
      nanoparticles.
AB  - This study discusses the strategies on sample preparation to acquire images with
      sufficient quality for size characterization by scanning electron microscope
      (SEM) using two commercial ZnO nanoparticles of different surface properties as a
      demonstration. The central idea is that micrometer sized aggregates of ZnO in
      powdered forms need to firstly be broken down to nanosized particles through an
      appropriate process to generate nanoparticle dispersion before being deposited on
      a flat surface for SEM observation. Analytical tools such as contact angle,
      dynamic light scattering and zeta potential have been utilized to optimize the
      procedure for sample preparation and to check the quality of the results.
      Meanwhile, measurements of zeta potential values on flat surfaces also provide
      critical information and save lots of time and efforts in selection of suitable
      substrate for particles of different properties to be attracted and kept on the
      surface without further aggregation. This simple, low-cost methodology can be
      generally applied on size characterization of commercial ZnO nanoparticles with
      limited information from vendors.

PMID- 29567234
TI  - Silver nanoparticle biosynthesis by using phenolic acids in rice husk extract as
      reducing agents and dispersants.
AB  - Rice husk extract, obtained using acid and alkali pretreatment extraction (AAPE),
      contains bioactive compounds and exhibits reducing abilities. Phenolic
      composition in rice husk extract was analyzed and the mechanism of silver
      nanoparticle (AgNP) biosynthesis by using AAPE rice husk extract was investigated
      in this study. Stable and spherically shaped AgNPs with a size of <15 nm were
      prepared under the following conditions: 0.001 M AgNO3, AAPE rice husk extract
      diluted 10 times, pH 10, and reacted at 25  degrees C for 60 min. Synergistic
      effects among phenolic acids contributed to the formation of AgNPs, with the
      acids acting as excellent reducing agents (owing to their abundant hydroxyl
      groups) and excellent dispersants (owing to their derived CO groups), which
      enhanced the NPs' stability. Caffeic acid (CA) was demonstrated to synthesize
      AgNPs independently and is suggested to be the most crucial compound for reducing
      Ag+ during the biosynthesis with rice husk extract. A possible mechanism and
      reaction process for the formation of AgNPs synthesized using CA in rice husk
      extracts is proposed.

PMID- 29567235
TI  - An investigation of the olive phenols activity as a natural medicine.
AB  - The natural antioxidants of olive oil have phenolic structure and their
      activities are related to the formation of stable derivatives. In this study, the
      single components of the phenolic fraction of olive oil (1,4-hydroquinone,
      Semiquinone and 1,4-benzoquinone) have been studied as theoretical by using DFT
      (Density functional Theory). The behaviors of phenolic compounds of olive against
      to the alkyl peroxy radicals were investigated. Our data show that 1,4
      benzoquinone is the best electron transfer agent in primary metabolic processes
      to human life. The frontier orbital gap, namely HOMO (highest occupied molecular
      orbital)-LUMO (lowest unoccupied molecular orbital) gap is the smallest for 1,4
      benzoquinone. Hence, it is more stable than the others in blood. The natural
      phenolic compound's mechanism of many plants can be explained by using DFT method
      without consuming time and money. In this study, we have indicated the behaviors
      of natural antioxidants of olive oil's single components phenolic structure in
      blood phase.

PMID- 29567236
TI  - Pt-MWCNT modified carbon electrode strip for rapid and quantitative detection of
      H2O2 in food.
AB  - A single-use screen-printed carbon electrode strip was designed and fabricated.
      Nanohybrids, prepared by deposition of platinum (Pt) nanoparticles on multi-wall
      carbon nanotube (MWCNT), was modified on the surface of screen-printed carbon
      electrode for the development of a fast, sensitive and cost-effective hydrogen
      peroxide (H2O2) detection amperometric sensor strip. With Pt-MWCNT nanohybrids
      surface modification, current generated in response to H2O2 by the screen-printed
      carbon electrode strip was enhanced 100 fold with an applied potential of 300 mV.
      Quality of as-prepared electrode strip was assured by the low coefficient of
      variation (CV) (<5%) of currents measured at 5 s. Three linear detection ranges
      with sensitivity of 75.2, 120.7, and 142.8 MUA mM-1 cm-2 were observed for H2O2
      concentration in the range of 1-15 mM, 0.1-1 mM, and 10-100 MUM, respectively.
      The lowest H2O2 concentration could be measured by the as-prepared strip was 10
      MUM. H2O2 levels in green tea infusion and pressed Tofu could be rapidly detected
      with results comparable to that measured by ferrous oxidation xylenol orange
      (FOX) assay and peroxidase colorimetric method.

PMID- 29567237
TI  - Determination of total mercury in seafood by ion-selective electrodes based on a
      thiol functionalized ionic liquid.
AB  - A mercury(II) ion-selective electrode with an ionic liquid (IL), 1-methyl-2
      butylthioimidazolium bis(trifluoromethanesulphonyl)imide ([C1C4Sim]NTf2) as
      active material was constructed. Parameters affecting the performance of the
      electrodes such as the dosages of the IL and carbon nanotubes and the aqueous pH
      values were investigated. Experimental results indicated that the optimal
      composition of the electrode filling material was 47.6% [C1C4Sim]NTf2, 47.6%
      tetrabutylphosphonium bis(trifluoromethanesulphonyl)imide (TBPNTf2) and 4.8%
      carboxylic multi-walled carbon nanotubes (MWCNTs-COOH). Under the selected
      conditions, the proposed electrodes showed a good linear response in the
      concentration range of 10-10-10-5 mol L-1 and had a detection limit of 4.1 * 10
      11 mol L-1. No great interference from common metal ions was found. The proposed
      electrodes were applied to determine Hg2+ in seafood samples; the results were
      comparable to those of the direct mercury analyzer.

PMID- 29567238
TI  - Characteristics of fucose-containing polysaccharides from submerged fermentation
      of Agaricus blazei Murill.
AB  - Fucose is one of important residues of recognition pattern for many immune cells.
      In this study, we characterized bioactive fucose-containing acidic
      polysaccharides from submerged fermentation of Agaricus blazei Murill. We
      obtained the polysaccharides through a cell-based activity-guided strategy, and
      used carbohydrate recognition monoclonal antibodies based Enzyme-Linked Immuno
      Sorbent Assay (ELISA) along with methylation and NMR analyses to investigate the
      structural characteristics of the polysaccharides. The polysaccharides had Mw of
      3.5 * 105 Da. The major sugars were l-fucose, l-arabinose, d-galactose, d-xylose,
      and d-galacturonic acid in the molar ratio of 6.4, 15.5, 28.5, 14.7, and 25.0%
      with a small amount of d-glucose, d-mannose, l-rhamnose, and d-glucuronic acid.
      Results indicated that the bioactive polysaccharides consisted of a (1,4)-Galp
      and (1,4)-GalAp back bone; (1,2)-Xyl and (1,2)-Rha might also comprise backbone
      or constitute side chain; linkage (1,5)-Ara and terminal fucosyl residues were
      also involved in the polysaccharides. Regarding bioactivity, removal of the
      terminal l-fucosyl residues reduced the TNF-alpha cytokine stimulating activity
      of the polysaccharides in a RAW 264.7 macrophage cell-line test, whereas NF
      kappaB and TLR4 affected the polysaccharide-induced TNF-alpha production.

PMID- 29567239
TI  - HPTLC-FLD-SERS as a facile and reliable screening tool: Exemplarily shown with
      tyramine in cheese.
AB  - The serious cytotoxicity of tyramine attracted marked attention as it induced
      necrosis of human intestinal cells. This paper presented a novel and facile high
      performance thin-layer chromatography (HPTLC) method tailored for screening
      tyramine in cheese. Separation was performed on glass backed silica gel plates,
      using methanol/ethyl acetate/ammonia (6/4/1 v/v/v) as the mobile phase. Special
      efforts were focused on optimizing conditions (substrate preparation, laser
      wavelength, salt types and concentrations) of surface enhanced Raman spectroscopy
      (SERS) measurements directly on plates after derivatization, which enabled
      molecule-specific identification of targeted bands. In parallel, fluorescent
      densitometry (FLD) scanning at 380</400 nm offered satisfactory quantitative
      performances (LOD 9 ng/zone, LOQ 17 ng/zone, linearity 0.9996 and %RSD 6.7).
      Including a quick extraction/cleanup step, the established method was
      successfully validated with different cheese samples, both qualitatively
      (straightforward confirmation) and quantitatively (recovery rates from 83.7 to
      108.5%). Beyond this application, HPTLC-FLD-SERS provided a new horizon in fast
      and reliable screening of sophisticated samples like food and herb drugs,
      striking an excellent balance between specificity, sensitivity and simplicity.

PMID- 29567240
TI  - Production of antioxidant and ACE-inhibitory peptides from Kluyveromyces
      marxianus protein hydrolysates: Purification and molecular docking.
AB  - Kluyveromyces marxianus protein hydrolysates were prepared by two different
      sonicated-enzymatic (trypsin and chymotrypsin) hydrolysis treatments to obtain
      antioxidant and ACE-inhibitory peptides. Trypsin and chymotrypsin hydrolysates
      obtained by 5 h, exhibited the highest antioxidant and ACE-inhibitory activities.
      After fractionation using ultrafiltration and reverse phase high performance
      liquid chromatography (RP-HPLC) techniques, two new peptides were identified. One
      fragment (LL-9, MW = 1180 Da) with the amino acid sequence of Leu-Pro-Glu-Ser-Val
      His-Leu-Asp-Lys showed significant ACE inhibitory activity (IC50 = 22.88 MUM)
      while another peptide fragment (VL-9, MW = 1118 Da) with the amino acid sequence
      of Val-Leu-Ser-Thr-Ser-Phe-Pro-Pro-Lys showed the highest antioxidant and ACE
      inhibitory properties (IC50 = 15.20 MUM, 5568 MUM TE/mg protein). The molecular
      docking studies revealed that the ACE inhibitory activities of VL-9 is due to
      interaction with the S2 (His513, His353, Glu281) and S'1 (Glu162) pockets of ACE
      and LL-9 can fit perfectly into the S1 (Thr345) and S2 (Tyr520, Lys511, Gln281)
      pockets of ACE.

PMID- 29567241
TI  - Compositional analyses of white, brown and germinated forms of popular Malaysian
      rice to offer insight into the growing diet-related diseases.
AB  - Diet-related metabolic diseases, and especially obesity, are metabolic disorders
      with multifactorial aetiologies. Diet has been a cornerstone in both the
      aetiology and management of this metabolic disorders. Rice, a staple food for
      over half of the world's population, could be exploited as part of the solution
      to check this menace which has been skyrocketing in the last decade. The present
      study investigated nine forms of rice from three widely grown Malaysian rice
      cultivars for in vitro and in vivo (glycaemic index and load) properties that
      could translate clinically into a lower predisposition to diet-related diseases.
      The germinated brown forms of MRQ 74 and MR 84 rice cultivars had high amylose
      content percentages (25.7% and 25.0%), high relative percentage antioxidant
      scavenging abilities of 85.0% and 91.7%, relatively low glycaemic indices (67.6
      and 64.3) and glycaemic load (32.3 and 30.1) values, and modest glucose uptake
      capabilities of 33.69% and 31.25%, respectively. The results show that all things
      being equal, rice cultivars that are germinated and high in amylose content when
      compared to their white and low amylose counterparts could translate into a lower
      predisposition to diet-related diseases from the dietary point of view in
      individuals who consume this cereal as a staple food.

PMID- 29567242
TI  - Sialoglycoprotein isolated from eggs of Carassius auratus promotes fracture
      healing in osteoporotic mice.
AB  - In this study, open tibial fracture surgery was performed on mice with
      ovariectomy induced osteoporosis to investigate the effect of a treatment with
      sialoglycoprotein isolated from Carassius auratus eggs (Ca-SGP) on fracture
      healing. Dynamic histological analysis showed that Ca-SGP promoted the generation
      of cartilage callus on day 5 post-surgery, then facilitated the transformation of
      the cartilage callus to bony callus on days 11 and 24 post-surgery, and enhanced
      the remodeling of bony callus on 35 day post-surgery. Moreover, Ca-SGP
      significantly decreased the secretion of TNF-alpha and IL-1beta in serum on day 5
      post-surgery, thus inhibiting the negative spread of the inflammatory reaction.
      On day 11 post-surgery, Ca-SGP clearly decreased the serum level and the mRNA
      expression of Aggrecan but also increased the secretion and the expression of
      VEGF and MMP13, thus promoting the degradation of the cartilage matrix and
      vascular invasion. On day 24 post-surgery, Ca-SGP remarkably increased the mRNA
      expression of osteogenesis markers Col1a and OCN, and increased callus BV/TV and
      Tb.N, this facilitating the formation of woven bone. On day 35 post-surgery, Ca
      SGP enhanced the transformation of woven bone into lamellar bone and improved the
      callus biomechanical property. In conclusion, Ca-SGP promoted fracture healing in
      osteoporotic mice by accelerating endochondral ossification.

PMID- 29567243
TI  - Determination of ractopamine and salbutamol in pig hair by liquid chromatography
      tandem mass spectrometry.
AB  - A liquid chromatography tandem mass spectrometric method was developed for the
      determination of two beta-agonists (ractopamine and salbutamol) in pig hair
      samples. An isotope of ractopamine-d5 or salbutamol-d6 as an internal standard
      was used to carry out quantitative analysis. Concentrated sodium hydroxide was
      used to pretreat hair samples and then purified by the solid phase extraction
      (SPE) procedure. The extracted solution was evaporated and reconstituted for
      injection in the instrument with electrospray ionization (ESI) operating in a
      positive multiple-reaction-monitoring (MRM) mode. Ractopamine and salbutamol
      separation were performed on C18 analytical column under gradient condition. The
      internal standard calibration curve was linear in the range of concentration from
      0.5 to 100 ng mL-1 (R2 > 0.995). Recoveries of this method estimated at three
      spiked concentrations of 100, 250 and 500 ng mL-1 in pig hair samples, were 79
      82% for ractopamine and 77-96% for salbutamol. The corresponding inter-day and
      intra-day precisions expressed as relative standard deviation (RSD %) were 3.8
      6.4% and 3.8-8.6%, respectively. The analytical time for one sample was 8 min.
      The detection limit of this method was 0.6 and 8.3 ng mL-1 for ractopamine and
      salbutamol, respectively. This developed method can be applied for monitoring the
      use of the beta-agonists salbutamol and ractopamine in swine feed incurred pig
      hair.

PMID- 29567244
TI  - Effects of vinegar-egg on growth inhibition, differentiation human leukemic U937
      cells and its immunomodulatory activity.
AB  - Vinegar and eggs have rich nutrients. In this study, the mixed form of both
      derived products, vinegar-egg solution and its products (vinegar-egg concentrate
      and vinegar-egg condensate) were chosen for an assessment of their biological
      activity. To further our understanding regarding the anticancer and
      immunomodulatory effects of vinegar-egg, we investigated its effects on the
      proliferation and differentiation of U937 cells. Vinegar-egg was treated using
      spray drying, freeze drying and vacuum concentration and used to stimulate human
      mononuclear cells. The conditioned media obtained from these cultures by
      filtration were used to treat U937 cells. Three conditioned media inhibited U937
      cell growth by 22.1-67.25% more effectively than PHA-treated control (22.53%).
      CD11b and CD14 expression on the treated U937 cells were 29.1-45.4% and 31.6
      47.2%, respectively. High levels of cytokines IL-1beta, IFN-gamma and TNF-alpha
      were detected in the three conditioned media. Vinegar-egg stimulates human
      mononuclear cells to secrete cytokines, which inhibit the growth of U937 cells
      and induce their differentiation.

PMID- 29567245
TI  - Immunochemical assay with monoclonal antibodies for detection of staphylococcal
      enterotoxin H.
AB  - Staphylococcal enterotoxins cause food poisoning of various degrees of severity.
      For milk and meat products, there is a high probability of contamination with
      staphylococcal enterotoxin H (SEH). In this regard specific and sensitive methods
      are required to be developed for its detection and monitoring. In this work, the
      gene seh was expressed and a preparation of recombinant toxin was obtained. Using
      hybridoma technology, a panel of high-affinity monoclonal antibodies (mAbs) to
      SEH was produced. The antibodies were characterized and shown to have no cross
      reactivity towards the main staphylococcal enterotoxins (A, B, C1, D, E, G and
      I). Based on these mAbs, a method for specific and quantitative detection of SEH
      was developed in the format of sandwich enzyme immunoassay (linear range, 0.2-3
      ng/ml). All the mAbs produced revealed SEH by immunoblotting. Immunochemical
      analysis of the culture fluids of staphylococcal isolates obtained from the milk
      of mastitis-infected cows by immunoblotting and sandwich enzyme immunoassay
      demonstrated the conformity of these methods. Using the developed method, the
      toxin was revealed in blood serum and liquid food products practically to 100%.
      From non-liquid foods, it was shown to be extracted to a maximum with a buffer of
      pH 4.0-4.5.

PMID- 29567246
TI  - Rapid screening of toxic glycoalkaloids and micronutrients in edible nightshades
      (Solanum spp.).
AB  - African indigenous vegetables (AIVs) because of their nutrient density have the
      unique potential to reduce micronutrient deficiencies in sub-Saharan Africa, yet
      some may also contain anti-nutritive compounds. Vegetable nightshades from
      Solanum americanum, Solanum nigrum, Solanum scabrum and Solanum villosum are
      among the major AIVs used as a leafy vegetables and consumed regularly in many
      countries in sub-Sahara Africa. These under-recognized food crops have not been
      subjected to extensive studies for their nutritional and antinutritive factors.
      In this study, 15 entries of the vegetable nightshades were field-grown and the
      leaves which are the consumed product of commerce chemically profiled by LC/ESI
      MS. Twenty-three flavones, eight saponins, and two glycoalkaloids along with a
      phenolic acid of chlorogenic acid were identified by MS and UV data. Anti
      nutrient glycoalkaloids were quantified as total aglycones after acidic
      hydrolysis using MS detection and found to be within safe-consumption thresholds
      by comparison with the glycoalkaloid level in the globally consumed Solanum
      member eggplants. Edible nightshades were also found to be sources of beta
      carotene, vitamin E and total polyphenols and exhibited high antioxidant
      activity. Results of this study support that consumption of vegetable nightshades
      are safe from the presence of glycoalkaloids and thus, can contribute to the
      reduction of micronutrient deficiency in sub-Sahara Africa.

PMID- 29567247
TI  - Antibacterial activity of propolins from Taiwanese green propolis.
AB  - Taiwanese green propolis is a prenylated flavonoid rich honeybee product and
      propolins isolated from Taiwanese green propolis exert a broad spectrum of
      biological activities, such as anti-cancer and anti-oxidant. However, the anti
      bacterial effects of Taiwanese green propolis or propolins are still poorly
      understood. In the current study, the antibacterial effects of Taiwanese green
      propolis and propolins were evaluated. Results show that the maximum dry matter
      yields of Taiwanese green propolis were observed in the 95% and 99.5% ethanol
      extracts compared to other extraction methods. Consistently, the highest
      concentration of propolins C, D, F and G from Taiwanese green propolis was
      obtained in 95% and 99.5% ethanol extracts. Propolins inhibited the growth of
      gram-positive bacterial strains (Staphylococcus aureus, Bacillus subtilis,
      Listeria monocytogenes and Paenibacillus larvae). The average minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) of propolins
      from ethanol extracts were 20 MUg/ml. Among the propolins, propolin C had the
      highest antibacterial activity. Furthermore, Taiwanese green propolis also showed
      antibacterial activity against methicillin-resistant S. aureus (MRSA). In
      conclusion, these results demonstrate that Taiwanese green propolis and propolins
      have significant antibacterial activity, particularly against gram-positive
      bacterial strains.

PMID- 29567248
TI  - The integration of multi-platform MS-based metabolomics and multivariate analysis
      for the geographical origin discrimination of Oryza sativa L.
AB  - For the authentication of white rice from different geographical origins, the
      selection of outstanding discrimination markers is essential. In this study, 80
      commercial white rice samples were collected from local markets of Korea and
      China and discriminated by mass spectrometry-based untargeted metabolomics
      approaches. Additionally, the potential markers that belong to sugars & sugar
      alcohols, fatty acids, and phospholipids were examined using several multivariate
      analyses to measure their discrimination efficiencies. Unsupervised analyses,
      including principal component analysis and k-means clustering demonstrated the
      potential of the geographical classification of white rice between Korea and
      China by fatty acids and phospholipids. In addition, the accuracy, goodness-of
      fit (R2), goodness-of-prediction (Q2), and permutation test p-value derived from
      phospholipid-based partial least squares-discriminant analysis were 1.000, 0.902,
      0.870, and 0.001, respectively. Random Forests further consolidated the
      discrimination ability of phospholipids. Furthermore, an independent validation
      set containing 20 white rice samples also confirmed that phospholipids were the
      excellent discrimination markers for white rice between two countries. In
      conclusion, the proposed approach successfully highlighted phospholipids as the
      better discrimination markers than sugars & sugar alcohols and fatty acids in
      differentiating white rice between Korea and China.

PMID- 29567249
TI  - Mulberry Leaf Extracts prevent obesity-induced NAFLD with regulating
      adipocytokines, inflammation and oxidative stress.
AB  - Mulberry (Morus alba) leaf has been used in Chinese medicine as the remedy for
      hyperlipidemia and metabolic disorders. Recent report indicated Mulberry leaf
      extract (MLE) attenuated dyslipidemia and lipid accumulation in high fat diet
      (HFD)-fed mice. Non-alcoholic fatty liver (NAFLD) is generally considered as the
      liver component of metabolic syndrome. The hepatic lipid infiltration induces
      oxidative stress, and is associated with interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) which are regulated by the leptin and adiponectin. MLE
      could prevent obesity-related NAFLD via downregulating the lipogenesis enzymes
      while upregulating the lipolysis markers. Treatment of MLE, especially at 2%,
      enhanced the expression of superoxide dismutase (SOD) and clenched the oxidative
      stress of liver. MLE decreased the plasma level of leptin but increased
      adiponectin. The advantage of MLE is supposed mainly attributed to chlorogenic
      acid derivative. We suggest MLE, with promising outcome of research, could be
      nutraceutical to prevent obesity and related NAFLD.

PMID- 29567250
TI  - Simultaneous quantification of eight organic acid components in Artemisia
      capillaris Thunb (Yinchen) extract using high-performance liquid chromatography
      coupled with diode array detection and high-resolution mass spectrometry.
AB  - We aim to determine the chemical constituents of Yinchen extract and Yinchen
      herbs using high-performance liquid chromatography coupled with diode array
      detection and high-resolution mass spectrometry. The method was developed to
      analyze of eight organic acid components of Yinchen extract (including
      neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, 1,3
      dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and
      4,5-dicaffeoylquinic acid). The separation was conducted using an Agilent TC-C18
      column with acetonitrile - 0.2% formic acid solution as the mobile phases under
      gradient elution. The analytical method was fully validated in terms of
      linearity, sensitivity, precision, repeatability as well as recovery, and
      subsequently the method was performed for the quantitative assessment of Yinchen
      extracts and Yinchen herbs. In addition, the changes of selected markers were
      studied when Yinchen herbs decocting in water and isomerization occurred between
      the chlorogenic acids. The proposed method enables both qualitative and
      quantitative analyses and could be developed as a new tool for the quality
      evaluation of Yinchen extract and Yinchen herbs. The changes of selected markers
      in water decoction process could give us some novel idea when studying the link
      between substances and drug efficacy.

PMID- 29567251
TI  - Effect of drying processes on prenylflavonoid content and antioxidant activity of
      Epimedium koreanum Nakai.
AB  - Epimedium koreanum Nakai is a famous Chinese herbal medicine for the treatment of
      impotence, osteoporosis, immune suppression and cardiovascular diseases. Drying
      is the most common and fundamental procedure in post-harvest processing of E.
      koreanum, which contributes to the variations of flavonoid content, especially
      prenylflavonoids, the bioactive components. In present study, effect of drying
      processes on flavonoid content and antioxidant activity were investigated. High
      performance liquid chromatography coupled with diode-array detection and
      electrospray ionization quadrupole time-of-flight tandem mass spectrometry
      methods were employed. Twenty seven compounds were identified and 11 of them,
      including eight prenylflavonoids and three other types of flavonoids, were
      further quantified. The antioxidant activity of E. koreanum was evaluated by the
      2,2-diphenyl-1-picrylhydrazyl free radical scavenging method. The results showed
      that content of the eight prenylflavonoids exhibited significant variations after
      different drying processes, especially icariin and baohuoside I. The variation
      tendency of antioxidant activity was positively correlated with the content of
      total flavonoid, afzelin and icariin.

PMID- 29567252
TI  - General survey of Fructus Psoraleae from the different origins and chemical
      identification of the roasted from raw Fructus Psoraleae.
AB  - Fructus Psoraleae, a traditional Chinese medicine, is widely used for preventing
      and treating various diseases such as vitiligo, osteoporosis and psoriasis.
      Coumarin, such as psoralenoside, isopsoralenoside, psoralen and isopsoralen, are
      important compounds in Fructus Psoraleae. In our study, ultra performance liquid
      chromatography coupled with diode array detector was employed for an excellent
      method validation for simultaneous quantification of psoralenoside,
      isopsoralenoside, psoralen and isopsoralen, which was further applied in
      performing general survey of Fructus Psoraleae from the different origins and
      chemical identification of the roasted from raw Fructus Psoraleae in the light of
      illuminating the transformed rule of psoralenoside and isopsoralenoside. There is
      a reciprocal relationship between (iso)psoralenoside and (iso)psoralen, and the
      total content remains balance in Fructus Psoraleae from the different origins. In
      addition, we found that (iso)psoralenoside in the powder of the raw Fructus
      Psoraleae could be easily transformed into (iso)psoralen in methanol aqueous
      solution, especially above 50% water, rather than the roasted one. Thus, we
      proposed a hypothesis that transformation between (iso)psoralenoside and
      (iso)psoralen was hindered by inactivation of beta-glucosidase in the process of
      roasting Fructus Psoraleae, which was further verified by observing
      transformation of (iso)psoralenoside under the different conditions, such as
      temperature, pH and beta-glucosidase. Therefore, we developed a feasible method
      to distinguish the roasted from raw Fructus Psoraleae by observing conversion
      from (iso)psoralenoside to (iso)psoralen in 50% methanol aqueous solution. In
      summary, these results pave the way for elevating quality standard for Fructus
      Psoraleae and distinguishing the salt-processed from raw Fructus Psoraleae.

PMID- 29567253
TI  - Nanoparticle based bio-bar code technology for trace analysis of aflatoxin B1 in
      Chinese herbs.
AB  - A novel and sensitive assay for aflatoxin B1 (AFB1) detection has been developed
      by using bio-bar code assay (BCA). The method that relies on polyclonal
      antibodies encoded with DNA modified gold nanoparticle (NP) and monoclonal
      antibodies modified magnetic microparticle (MMP), and subsequent detection of
      amplified target in the form of bio-bar code using a fluorescent quantitative
      polymerase chain reaction (FQ-PCR) detection method. First, NP probes encoded
      with DNA that was unique to AFB1, MMP probes with monoclonal antibodies that bind
      AFB1 specifically were prepared. Then, the MMP-AFB1-NP sandwich compounds were
      acquired, dehybridization of the oligonucleotides on the nanoparticle surface
      allows the determination of the presence of AFB1 by identifying the
      oligonucleotide sequence released from the NP through FQ-PCR detection. The bio
      bar code techniques system for detecting AFB1 was established, and the
      sensitivity limit was about 10-8 ng/mL, comparable ELISA assays for detecting the
      same target, it showed that we can detect AFB1 at low attomolar levels with the
      bio-bar-code amplification approach. This is also the first demonstration of a
      bio-bar code type assay for the detection of AFB1 in Chinese herbs.

PMID- 29567254
TI  - Comprehensive two-dimensional APTES-decorated MCF7-cell membrane chromatographic
      system for characterizing potential anti-breast-cancer components from Yuanhu
      Baizhi herbal medicine pair.
AB  - Rhizoma corydalis and Radix Angelicae Dahurica (Yuanhu-Baizhi) herbal medicine
      pair has been used for thousands of years and has been reported to be potentially
      active in recent cancer therapy. But the exact active components or fractions
      remain unclear. In this study, a new comprehensive two-dimensional (2D) 3
      aminopropyltriethoxysilane (APTES)-decorated MCF7-cell membrane chromatography
      (CMC)/capcell-C18 column/time-of-flight mass spectrometry system was established
      for screening potential active components and clarifying the active fraction of
      Yuanhu-Baizhi pair. APTES was modified on the surface of silica, which can
      provide an amino group to covalently link cell membrane fragments with the help
      of glutaraldehyde in order to improve the stability and column life span of the
      MCF7 CMC column. The comprehensive 2D MCF7-CMC system showed good separation and
      identification abilities. Our screen results showed that the retention components
      are mainly from the alkaloids in Yuanhu (12 compounds) and the coumarins (10
      compounds) in Baizhi, revealing the active fractions of Yuanhu-Baizhi herbal
      medicine pair. Oxoglaucine, protopine, berberine, osthole, isopimpinellin and
      palmitic acid were selected as typical components to test the effects on cell
      proliferation and their IC50 were calculated as 38.17 MUM, 29.45 MUM, 45.42 MUM,
      132.7 MUM, 156.8 MUM and 90.5 MUM respectively. Cell apoptosis assay showed that
      the drug efficacy was obtained mainly through inducing cell apoptosis.
      Furthermore, a synergistic assay results demonstrated that oxoglaucine
      (representative of alkaloids from Yuanhu) and isopimpinellin (representative of
      coumarins from Baizhi) showed significant synergistic efficacy with GFT,
      indicating that these components may act on other membrane receptors. The
      proposed 2D CMC system could also be equipped with other cells for further
      applications. Besides, the follow-up in-vitro experimental strategy using cell
      proliferation assay, cell apoptosis assay and synergistic assay proved to be a
      practical way to confirm the active fractions of herbal medicine.

PMID- 29567255
TI  - Stability-indicating spectrofluorimetric method with enhanced sensitivity for
      determination of vancomycin hydrochloride in pharmaceuticals and spiked human
      plasma: Application to degradation kinetics.
AB  - Based on investigating the relative fluorescence intensity of vancomycin
      hydrochloride (VCM) in methanol, a simple, highly sensitive, time-saving and
      specific spectrofluorimetric method was developed and validated. VCM fluorescence
      was measured at 335 nm when excited at 268 nm. Excellent linearity is obeyed in
      the concentration range 1-100 ng/mL with a detection limit of 5.94 pg/mL, a
      quantitation limit of 18.03 pg/mL and a very good correlation coefficient (r =
      0.9999). Our method was applied to analyze VCM in pharmaceuticals as well as
      spiked human plasma. Moreover, VCM stability was studied when exposed to various
      degradation conditions such as oxidative, alkaline as well as acidic stress.
      Acidic and alkaline degradation kinetics of VCM was studied for the first time.
      The degradation follows pseudo-first-order kinetics. The apparent rate constants
      and half-life times were calculated. The Arrhenius equation was assessed and the
      activation energies of the degradation were also calculated. The developed method
      can be easily applied in quality control laboratories due to its sensitivity,
      specificity, simplicity and low cost.

PMID- 29567256
TI  - A validated capillary electrophoretic method for the determination of indacaterol
      and its application to a pharmaceutical preparation.
AB  - Indacaterol is a new inhaled ultra-long acting beta2-agonist. It has been
      recently approved in the European Union for the treatment of chronic obstructive
      pulmonary disease. This paper reports, for the first time, a method for the
      determination and validation of Indacaterol (IND) using an internal standard in
      capsules. Capillary electrophoretic separation was performed on an uncoated fused
      silica capillary (50 cm effective length, 75 MUm i.d.) and background electrolyte
      composed of 20 mmol L-1 of sodium tetraborate buffer, 15% (v/v) methanol (pH =
      10.0) with the application of 20 kV of potential; 10 s at 5 * 103 N m-2 (50 mbar)
      of injection time; and wavelength of 200 nm and 25  degrees C of temperature. The
      linearity was evaluated in the range of 4.90 * 10-6 mol L-1 (2.50 MUg mL-1) and
      3.94 * 10-5 mol L-1 (20.00 MUg mL-1), with R = 0.9993 for inter-day. LOD and LOQ
      values were 2.18 * 10-8 mol L-1 (0.011 MUg mL-1) and 7.25 * 10-8 mol L-1 (0.037
      MUg mL-1) for inter-day, respectively. The precision values were 0.50-1.06% for
      intra-day and 2.12% for inter-day as RSD%. The accuracy was tested by the
      standard addition method with the recovery values being between 98.79 and 99.09
      as percentages with RSD% interval of 0.01-0.80. The developed method was
      validated according to ICH guidelines. Indacaterol was successfully determined in
      Arcapta(r) capsule dosage form by the validated CE method with a relative error
      of 0.28%. The result was within the requirements of the USP 34-NF29. Therefore,
      the validated method may be used for the determination of Indacaterol in its
      capsules in quality control laboratories.

PMID- 29567257
TI  - Pharmacokinetics, bioavailability, tissue distribution and excretion of
      tangeretin in rat.
AB  - Tangeretin, 4',5,6,7,8-pentamethoxyflavone, is one of the major
      polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels
      of sweet oranges and mandarins. Tangeretin has been reported to possess several
      beneficial bioactivities including anti-inflammatory, anti-proliferative and
      neuroprotective effects. To achieve a thorough understanding of the biological
      actions of tangeretin in vivo, our current study is designed to investigate the
      pharmacokinetics, bioavailability, distribution and excretion of tangeretin in
      rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax
      and t1/2 were 0.87 +/- 0.33 MUg/mL, 340.00 +/- 48.99 min and 342.43 +/- 71.27
      min, respectively. Based on the area under the curves (AUC) of oral and
      intravenous administration of tangeretin, calculated absolute oral
      bioavailability was 27.11%. During tissue distribution, maximum concentrations of
      tangeretin in the vital organs occurred at 4 or 8 h after oral administration.
      The highest accumulation of tangeretin was found in the kidney, lung and liver,
      followed by spleen and heart. In the gastrointestinal tract, maximum
      concentrations of tangeretin in the stomach and small intestine were found at 4
      h, while in the cecum, colon and rectum, tangeretin reached the maximum
      concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered
      within 48 h after oral administration, concentrations were only 0.0026% and
      7.54%, respectively. These results suggest that tangeretin was mainly eliminated
      as metabolites. In conclusion, our study provides useful information regarding
      absorption, distribution, as well as excretion of tangeretin, which will provide
      a good base for studying the mechanism of its biological effects.

PMID- 29567258
TI  - A new strategy for choosing "Q-markers" via network pharmacology, application to
      the quality control of a Chinese medical preparation.
AB  - Due to its chemical complexity, proper quality control for a Chinese medical
      preparation (CMP) has been a great challenge. Choosing the appropriate quality
      markers (Q-markers) for quality control of CMP is an important work. Best of all,
      the chosen Q-markers are the main chemical compounds from the herbals as well as
      the active constituents of this CMP. Only in this way the established quality
      control system can really achieve the purpose of controlling the quality of CMP
      and ensuring the safely and effectively use of CMP. To achieve the purpose,
      network pharmacology combined with the contents of chemical compounds in the CMP
      has been used in this research. We took an anti-arrhythmic CMP, Shenxian-Shengmai
      oral liquid (SSOL), as an example. Firstly, UPLC-QTOF-MS/MS method was used to
      analyze the main components of SSOL. A total of 64 compounds were unambiguously
      or tentatively identified and 32 of them were further validated by reference
      compounds. Secondly, the network was constructed based on the identified
      compounds to predict the effective compounds related to cardiac arrhythmias.
      Based on the existing database and the operation method of topology, a method of
      double network analysis (DNAA) was proposed, from which 10 important targets in
      the pathway of arrhythmia were screened out, and 26 compounds had good
      antiarrhythmic activity. Based on the prediction results of network pharmacology
      along with the contents of the compounds in this CMP, ten representative
      compounds were chosen as the Q-markers for the quality control of SSOL. We find
      that five of these ten compounds, including danshensu, rosmarinic acid,
      salvianolic acid A, epimedin A and icariin, have antiarrhythmic activity. Then,
      the UPLC-DAD method was established as the control method for SSOL.

PMID- 29567259
TI  - In vitro and in vivo assessment of delivery of hydrophobic molecules and plasmid
      DNAs with PEO-PPO-PEO polymeric micelles on cornea.
AB  - The stability and bio-distribution of genes or drug complexes with poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, Pluronic F-68)
      polymeric micelles (PM) are essential for an effective nanosized PM delivery
      system. We used Forster resonance energy transfer (FRET) pairs with PM and
      measured the FRET ratio to assess the stability of PM in vitro and in vivo on the
      cornea. The FRET ratio reached a plateau at 0.8 with 3% PM. Differential scanning
      calorimetry measurement confirmed the complex formation of FRET pairs with PM.
      Confocal imaging with the fluorophores fluorescein isothiocyanate isomer I (FITC)
      and rhodamine B base (RhB) also showed the occurrence of FRET pairs in vitro. The
      fluorophores were mixed with 3% PM solution or the FITC-labeled PEO-PPO-PEO
      polymers (FITC-P) were mixed with RhB-labeled plasmids (RhB-DNA). In addition,
      the in vitro corneal permeation of FRET pair complexes with PM reached a 0.8 FRET
      ratio. One hour after eye drop administration, FRET pairs colocalized in the
      cytoplasm, and surrounded and entered the nuclei of cells in the cornea, and the
      polymers were located in the corneal epithelial layers, as detected through anti
      PEG immunohistochemistry. Furthermore, fluorescence colocalization in the
      cytoplasm and cell nucleus of the corneal epithelium was confirmed in tissues
      where RhB or RhB-DNA complexed with FITC-P was found to accumulate. We
      demonstrate that at a concentration of 3%, PM can encapsulate FRET pairs or RhB
      DNA and retain their integrity within the cornea 1 h after administration,
      suggesting the feasibility and stability of PEO-PPO-PEO polymers as a vehicle for
      drug delivery.

PMID- 29567260
TI  - Ultra-sensitive electrochemical sensing of acetaminophen and codeine in
      biological fluids using CuO/CuFe2O4 nanoparticles as a novel electrocatalyst.
AB  - Copper ferrite-copper oxide (CuO-CuFe2O4) nanoparticles as a semiconductor
      composite with p-n junction were synthesized by co-precipitation reaction. Then,
      a novel CuO-CuFe2O4 carbon paste modified electrode was fabricated which displays
      an effectual electrocatalytic response to the oxidation of acetaminophen (AC) and
      codeine (CO). A linear range of 0.01-1.5 MUmol L-1 and 0.06-10.0 MUmol L-1 with
      the detection limits of 0.007 MUmol L-1 and 0.01 MUmol L-1 were achieved for AC
      and CO, respectively. The practical usage of the proposed sensor revealed
      reasonable results for quantification of AC and CO in biological fluids.

PMID- 29567261
TI  - Triple-component nanocomposite films prepared using a casting method: Its
      potential in drug delivery.
AB  - The purpose of this study was to fabricate a triple-component nanocomposite
      system consisting of chitosan, polyethylene glycol (PEG), and drug for assessing
      the application of chitosan-PEG nanocomposites in drug delivery and also to
      assess the effect of different molecular weights of PEG on nanocomposite
      characteristics. The casting/solvent evaporation method was used to prepare
      chitosan-PEG nanocomposite films incorporating piroxicam-beta-cyclodextrin. In
      order to characterize the morphology and structure of nanocomposites, X-ray
      diffraction technique, scanning electron microscopy, thermogravimetric analysis,
      and Fourier transmission infrared spectroscopy were used. Drug content uniformity
      test, swelling studies, water content, erosion studies, dissolution studies, and
      anti-inflammatory activity were also performed. The permeation studies across rat
      skin were also performed on nanocomposite films using Franz diffusion cell. The
      release behavior of films was found to be sensitive to pH and ionic strength of
      release medium. The maximum swelling ratio and water content was found in HCl
      buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH
      7.4. The release rate constants obtained from kinetic modeling and flux values of
      ex vivo permeation studies showed that release of piroxicam-beta-cyclodextrin
      increased with an increase in concentration of PEG. The formulation F10
      containing 75% concentration of PEG showed the highest swelling ratio (3.42+/
      0.02) in HCl buffer pH 1.2, water content (47.89+/-1.53%) in HCl buffer pH 1.2,
      maximum cumulative drug permeation through rat skin (2405.15+/-10.97 MUg/cm2) in
      phosphate buffer pH 7.4, and in vitro drug release (35.51+/-0.26%) in sequential
      pH change mediums, and showed a significantly (p<0.0001) higher anti-inflammatory
      effect (0.4 cm). It can be concluded from the results that film composition had a
      particular impact on drug release properties. The different molecular weights of
      PEG have a strong influence on swelling, drug release, and permeation rate. The
      developed films can act as successful drug delivery approach for localized drug
      delivery through the skin.

PMID- 29567262
TI  - Oxidative stress evoked damages leading to attenuated memory and inhibition of
      NMDAR-CaMKII-ERK/CREB signalling on consumption of aspartame in rat model.
AB  - Many controversial reports are available on the use of aspartame as it releases
      methanol as one of its metabolite during metabolism. The present study proposes
      to investigate whether long term (90 days) aspartame (40 mg/kg b.wt)
      administration could induce oxidative stress and alter the memory in Wistar
      strain male albino rats. To mimic the human methanol metabolism, methotrexate
      (MTX)-treated rats were included as a model to study the effects of aspartame.
      Wistar strain albino rats were administered with aspartame (40 mg/kg b.wt) orally
      and studied along with controls and MTX-treated controls. Aspartame interfered in
      the body weight and corticosterone levels in the rats. A marked increase in the
      mRNA and protein expression of neuronal nitric oxide synthase (nNOS) and induced
      nitric oxide synthase (iNOS) which resulted in the increased nitric oxide
      radical's level indicating that aspartame is a stressor. These reactive nitrogen
      species could be responsible for the altered cell membrane integrity and even
      cause death of neurons by necrosis or apoptosis. The animals showed a marked
      decrease in learning, spatial working and spatial recognition memory deficit in
      the Morris water maze and Y-maze performance task which could have resulted due
      to reduced hippocampal acetylcholine esterase (AChE) activity. The animal brain
      homogenate also revealed the decrease in the phosphorylation of NMDAR1-CaMKII
      ERK/CREB signalling pathway, which well documents the inhibition of
      phosphorylation leads to the excitotoxicity of the neurons and memory decline.
      This effect may be due to methanol which may also activate the NOS levels,
      microglia and astrocytes, inducing neurodegeneration in brain. Neuronal shrinkage
      of hippocampal layer due to degeneration of pyramidal cells revealed the abnormal
      neuronal morphology of pyramidal cell layers in the aspartame treated animals.
      These findings demonstrate that aspartame metabolites could be a contributing
      factor for the development of oxidative stress in the brain.

PMID- 29567263
TI  - Exploration of Wedelia chinensis leaf-assisted silver nanoparticles for
      antioxidant, antibacterial and in vitro cytotoxic applications.
AB  - Green synthetic route of silver nanoparticles (AgNPs) has already been proved to
      be an advantageous over other physico-chemical approaches due to its simplicity,
      cost effectiveness, ecofriendly and nontoxicity. In this finding, aqueous Wedelia
      chinensis leaf extract (WLE) mediated synthesis of AgNPs was approached. Surface
      plasmon resonance (SPR) band at 408 nm preliminary indicated the formation of
      AgNPs, while TEM and XRD characterization confirmed the formation of spherically
      shaped and crystalline AgNPs with an average size of 31.68 nm, respectively. The
      plausible biomolecules in the aqueous leaf extract responsible for the reduction
      and stabilization of AgNPs were identified by FTIR analysis and found to be
      polyphenolic groups in flavonoid. Further, synthesized AgNPs was explored for
      different biological applications. Biosynthesized AgNPs showed significant free
      radical scavenging activity as compared to Wedelia leaf extract and antibacterial
      activity against clinically isolated test pathogens where Gram-negative bacteria
      were found more susceptible to AgNPs than Gram-positive one. In addition, in
      vitro cytotoxic response was also evaluated on hepatocellular carcinoma Hep G2
      cell lines and showed a dose-dependent cytotoxic response with an IC50 value of
      25 MUg/mL.

PMID- 29567264
TI  - Ethical Considerations Arising From Surgeon Caseload Volume in Benign Gynecologic
      Surgery.

PMID- 29567265
TI  - Estrogen receptor beta activation within dorsal raphe nucleus reverses anxiety
      like behavior induced by food restriction in female rats.
AB  - Severe food restriction (FR), as observed in disorders like anorexia nervosa, has
      been associated to the reduction of estrogen levels, which in turn could lead to
      anxiety development. Estrogen receptors, mainly ERbeta type, are commonly found
      in the dorsal raphe nucleus (DRN) neurons, an important nucleus related to
      anxiety modulation and the primary source of serotonin (5-HT) in the brain.
      Taking together, these findings suggest an involvement of estrogen in anxiety
      modulation during food restriction, possibly mediated by ERbeta activation in
      serotonergic DRN neurons. Thus, the present study investigated the relationship
      between food restriction and anxiety-like behavior, and the involvement of DRN
      and ERbeta on the modulation of anxiety-like behaviors in animals subjected to
      FR. For that, female Fischer rats were grouped in control group, with free access
      to food, or a FR group, which received 40% of control intake during 14 days.
      Animals were randomly treated with 17beta-estradiol (E2), DPN (ERbeta selective
      agonist), or their respective vehicles, PBS and DMSO. Behavioral tests were
      performed on Elevated T-Maze (ETM) and Open Field (OF). Our results suggest that
      FR probably reduced the estrogen levels, since the remained in the non-ovulatory
      cycle phases, and their uterine weight was lower when compared to control group.
      The FR rats showed increased inhibitory avoidance latency in theETM indicating
      that FR is associated with the development of an anxiety-like state. The
      injections of both E2 and DPN into DRN of FR animals had an anxiolytic effect.
      Those data suggest thatanxiety-like behavior induced by FR could be mediated by a
      reduction of ERbeta activation in the DRN neurons, probably due to decreased
      estrogen levels.

PMID- 29567266
TI  - Early risk factors for mortality in children with seizure and/or impaired
      consciousness accompanied by fever without known etiology.
AB  - BACKGROUND: Children who present with seizure and/or impaired consciousness
      accompanied by fever without known etiology (SICF) may be diagnosed with either
      acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of
      AE cases are fatal, it is difficult to identify fatal cases among children with
      SICF, which are often critical by the time of diagnosis. Thus, early prediction
      of outcomes for children with SICF, prior to diagnosis, may help to reduce
      mortality associated with AE. The aim of the present study was to identify
      clinical and laboratory risk factors for mortality acquired within 6 h of onset
      among children with SICF. METHODS: We retrospectively reviewed the medical
      records of children who had been admitted to Kobe Children's Hospital (Kobe,
      Japan) with SICF between October 2002 and September 2015. We compared clinical
      and laboratory characteristics acquired within 6 h of onset and outcomes between
      survivors and non-survivors using univariate and multivariate analyses. RESULTS:
      The survivor and non-survivor groups included 659 and nine patients,
      respectively. All patients in the non-survivor group received a final diagnosis
      of AE. Univariate analysis revealed significant differences between the groups
      with regard to seizure duration and the following laboratory parameters:
      aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase,
      sodium, and lactate. The multivariate analysis identified AST as a significant
      independent factor associated with mortality. CONCLUSIONS: Elevation of AST
      within 6 h of onset is independently correlated with mortality in children with
      SICF. Our result may elucidate earlier intervention for patients with high risk
      of mortality.

PMID- 29567267
TI  - Determination of as-discarded methane potential in residential and commercial
      municipal solid waste.
AB  - Methane generation potential, L0, is a primary parameter of the first-order decay
      (FOD) model used for prediction and regulation of landfill gas (LFG) generation
      in municipal solid waste (MSW) landfills. The current US EPA AP-42 default value
      for L0, which has been in place for almost 20 years, is 100 m3 CH4/Mg MSW as
      discarded. Recent research suggests the yield of landfilled waste could be less
      than 60 m3 CH4/Mg MSW. This study aimed to measure the L0 of present-day
      residential and commercial as-discarded MSW. In doing so, 39 waste collection
      vehicles were sorted for composition before samples of each biodegradable
      fraction were analyzed for methane generation potential. Methane yields were
      determined for over 450 samples of 14 different biodegradable MSW fractions,
      later to be combined with moisture content and volatile solids data to calculate
      L0 values for each waste load. An average value of 80 m3 CH4/Mg MSW was
      determined for all samples with 95% of values in the interval 74-86 m3 CH4/Mg MSW
      as-discarded. While no statistically significant difference was observed,
      commercial MSW yields (mean 85, median 88 m3 CH4/Mg MSW) showed a higher average
      L0 than residential MSW (mean 75, median 71 m3 CH4/Mg MSW). Many methane
      potential values for individual fractions described in previous work were found
      within the range of values determined by BMP in this study.

PMID- 29567268
TI  - Altered hair endocannabinoid levels in mothers with childhood maltreatment and
      their newborns.
AB  - The endocannabinoid (EC) system possesses anti-inflammatory properties and seems
      to be altered in trauma-exposed individuals. In an intergenerational approach,
      this study investigated the link between childhood maltreatment (CM) experiences
      and alterations in the EC system. Hair samples of N = 142 mothers and N = 91
      newborns were analyzed, retrospectively assessing EC regulation during the last
      trimester of pregnancy with four ECs: 1-arachidonoylglycerol (1-AG), N
      oleoylethanolamide (OEA), N-stearoylethanolamide (SEA), and N
      palmitoylethanolamide (PEA). Compared to mothers without CM, hair of mothers with
      CM showed significantly higher levels of 1-AG and lower levels of SEA. Newborns
      of mothers with CM exhibited higher levels of 1-AG and OEA. Furthermore, the
      higher the severity of maternal CM, the lower were maternal SEA levels and the
      higher neonatal OEA levels. Findings indicate altered EC levels during the last
      trimester of pregnancy in mothers with CM and their developing fetus,
      highlighting potential intergenerational effects from one generation to the
      other.

PMID- 29567269
TI  - Quality assurance in CT: implementation of the updated national diagnostic
      reference levels using an automated CT dose monitoring system.
AB  - AIM: To evaluate the implementation of the updated computed tomography (CT)
      diagnostic reference levels (DRLs) from the German Federal Office for Radiation
      Protection into clinical routine using an automatic CT dose monitoring system.
      METHODS AND MATERIALS: CT radiation exposure was analysed before and after
      implementing the updated national DRLs into routine clinical work in 2016. After
      the implementation process, institutional CT protocols were mapped to the
      anatomical regions for which DRLs were provided. Systematically, protocols that
      exceeded the thresholds were optimised and analysed in detail. The CT radiation
      output parameters analysed were volumetric CT dose index (CTDIvol) and dose
      length product (DLP). Three radiologists evaluated subjective image quality using
      a three-point Likert scale. RESULTS: The study included 94,258 CT series (from
      27,103 CT examinations) in adult patients performed in 2016. When averaged over
      all body regions with available DRL, institutional CTDIvol/DLP values were always
      below the DRLs (65.2+/-32.9%/67.3+/-41.5% initially; 59.4+/-32%/60.5+/-39.9%
      after optimisation). Values exceeding the national DRLs were found for pelvis
      (n=268; CTDIvol 107.7+/-65.7%/DLP 106.3+/-79.3%), lumbar spine (n=91; 160.8+/
      74.7%/175.2+/-104.1%), and facial bones (n=527; 108+/-39%/152.7+/-75.7%). After
      optimisation, CTDIvol and DLP were 87.9+/-73%/87.8+/-80.8% for the pelvis, 67.8+/
      33.2%/74.5+/-50.6% for the lumbar spine and 95.1+/-45.8%/133.3+/-74.6% for the
      viscerocranium. CONCLUSION: An automatic CT dose monitoring system enabled not
      only comprehensive monitoring of a DRL implementation process but can also help
      to optimise radiation exposure.

PMID- 29567270
TI  - Pretreatment MRI features associated with diagnostic accuracy of post-treatment
      MRI after neoadjuvant chemotherapy.
AB  - AIM: To investigate whether pretreatment magnetic resonance imaging (MRI)
      features are associated with diagnostic accuracy of post-treatment MRI for
      predicting pathologic complete response (pCR) after neoadjuvant chemotherapy
      (NAC) in patients with breast cancer. MATERIALS AND METHODS: From January 2005
      and December 2016, 221 consecutive patients (mean age, 50 years; range, 20-81
      years) who had undergone NAC, breast MRI before and after NAC, and surgery for
      invasive breast cancer were enrolled. Pretreatment and post-treatment MRI images
      were reviewed. Radiological complete response (rCR) was defined as the absence of
      both early and late enhancement on MRI after NAC. The association of pretreatment
      MRI features and post-treatment MRI diagnostic accuracy was assessed by using
      logistic regression analysis. RESULTS: Among 221 patients, 60 (27.1%) underwent
      pCR after NAC. The diagnostic accuracy of post-treatment MRI was 84.2% (186/221).
      False-positive diagnosis occurred in 21 cases and false-negative diagnosis
      occurred in 14 cases. Of pretreatment features, the presence of peritumoural
      oedema (odds ratio, 3; 95% confidence interval [CI]: 1.1, 8.0; p=0.03) and HER2
      (human epidermal growth factor receptor 2)-positive status (odds ratio, 3.4; 95%
      CI: 1.2, 9.9; p=0.02) were significantly associated with false-positive MRI
      results. Dense fibroglandular tissue (odds ratio, 10.8; 95% CI: 1.1, 105.2;
      p=0.04), presence of rim enhancement (odds ratio, 7.5; 95% CI: 1.2, 38.3; p=0.02)
      and oestrogen receptor (ER)-positive status (odds ratio, 6.3; 95% CI: 1.2, 32.5;
      p=0.03) were significantly associated with false-negative MRI results.
      CONCLUSION: Pretreatment MRI features and cancer subtypes may be associated with
      diagnostic accuracy of post-treatment MRI after NAC in patients with breast
      cancer.

PMID- 29567271
TI  - Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review,
      meta-analysis, and Delphi exercise.

PMID- 29567273
TI  - Nursing in psychiatric inpatient wards: plus ca change, plus c'est la meme chose.

PMID- 29567274
TI  - Psychiatric/Mental Health Nursing in the 21st century: It's 'Deja vu' all over
      again!

PMID- 29567275
TI  - Hold on to the good: Change vs continuity in nursing on acute mental health care
      wards.

PMID- 29567272
TI  - The BET inhibitor INCB054329 reduces homologous recombination efficiency and
      augments PARP inhibitor activity in ovarian cancer.
AB  - OBJECTIVE: Homologous recombination (HR)-proficient ovarian tumors have poorer
      clinical outcomes and show resistance to poly ADP ribose polymerase inhibitors
      (PARPi). A subset of HR-proficient ovarian tumors show amplification in
      bromodomain and extra-terminal (BET) genes such as BRD4. We aimed to test the
      hypothesis that BRD4 inhibition sensitizes ovarian cancer cells to PARPi by
      reducing HR efficiency and increasing DNA damage. METHODS: HR-proficient ovarian
      cancer cell lines (OVCAR-3, OVCAR-4, SKOV-3, UWB1.289+BRCA1) were treated with
      BRD4-targeting siRNA, novel (INB054329, INCB057643) and established (JQ1) BET
      inhibitors (BETi) and PARPi (olaparib, rucaparib). Cell growth and viability were
      assessed by sulforhodamine B assays in vitro, and in SKOV-3 and ovarian cancer
      patient-derived xenografts in vivo. DNA damage and repair (pH2AX, RAD51 and BRCA1
      foci formation, and DRGFP HR reporter activity), apoptosis markers (cleaved PARP,
      cleaved caspase-3, Bax) and proliferation markers (PCNA, Ki67) were assessed by
      immunofluorescence and western blot. RESULTS: In cultured cells, inhibition of
      BRD4 by siRNA or INCB054329 reduced expression and function of BRCA1 and RAD51,
      reduced HR reporter activity, and sensitized the cells to olaparib-induced growth
      inhibition, DNA damage induction and apoptosis. Synergy was observed between all
      BETi tested and PARPi. INCB054329 and olaparib also co-operatively inhibited
      xenograft tumor growth, accompanied by reduced BRCA1 expression and
      proliferation, and increased apoptosis and DNA damage. CONCLUSIONS: These results
      provide strong rationale for using BETi to extend therapeutic efficacy of PARPi
      to HR-proficient ovarian tumors and could benefit a substantial number of women
      diagnosed with this devastating disease.

PMID- 29567276
TI  - Calycophyllum spruceanum BENTH ameliorates acute inflammation in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Calycophyllum spruceanum (Benth.) Hook. F. ex K.
      Schum. is widely distributed in the Amazonian region of Brazil, where it is
      popularly known as "mulateiro", "pau-mulato", "pau-mulato-de-varzea", "escorrega
      macaco" or "pau-marfim". Preparations of C. spruceanum barks are used in the form
      of tea, poultice or skin patches to treat stomach diseases, skin inflammation and
      uterus tumors. PURPOSE OF THE STUDY: To investigate in vivo the antinociceptive
      and anti-inflammatory activities of the hydroalcoholic extract of Calycophyllum
      spruceanum barks (HECSb) in order to validate its popular usage in inflammatory
      conditions. MATERIALS AND METHODS: Chemical analysis of HECSb was performed using
      the UHPLC-MS system. Mice were treated per oral with HECSb (5-5000 mg/kg) and
      evaluated for acute toxicity (during 15 days); motor activity (Rota rod test);
      body weight (up to 72 h); antinociceptive activity: writhes induced by 0.8%
      acetic acid; paw licking induced by 2.5% formalin; paw withdrawal (von Frey test)
      induced by carrageenan (300 MUg) or PGE2 (100 ng); anti-inflammatory (paw edema
      model). For histopathological analysis subplantar tissue fragments were collected
      1 h after paw edema induction. RESULTS: HECSb chemical analysis revealed the
      presence of caffeoylquinic derivatives, small organic acids, and phenolic
      compounds. HECSb showed antinociceptive effect, reducing the number of acetic
      acid-induced writhes by 72% at 120 mg/kg, paw licking (phase 2- Formalin test) by
      33% at 60 mg/kg and 49% at 120 mg/kg; and paw withdrawal elicited by carrageenan
      (53% at 120 mg/kg) and PGE2 (120 mg/kg) at 0.5 h (48%) and 1 h (45%). HECSb (120
      mg/kg) also inhibited the paw edema elicited both by carrageenan (48%) and PGE2
      (92%). Histopathological analysis (leukocyte infiltration, edema, focal areas of
      hemorrhage, vascular congestion) of HECSb treatment at 120 mg/kg demonstrated
      normal morphology [median 0 (0,1)] compared to PGE2, showing severe alterations
      [median 3 (2,3); p = 0,0035]. HECSb did not induce acute toxicity nor altered
      body mass or motor coordination. CONCLUSIONS: HECSb shows antinociceptive and
      anti-inflammatory effect in mice without inducing apparent acute toxicity.

PMID- 29567277
TI  - Castanea mollissima shell prevents an over expression of inflammatory response
      and accelerates the dermal wound healing.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Castanea mollissima shell (CMS) has been used for
      wound healing in China as traditional medicine. The shell is directly applied on
      the wounded skin as fine powder or as water maceration. AIM OF THE STUDY: To
      investigate the wound healing activity of CMS and the potential mechanism of anti
      inflammatory activity. MATERIALS AND METHODS: The effects of ethanol extract of
      CMS (ECMS) on nitricoxide (NO), tumor necrosis factor (TNF)-alpha and interleukin
      (IL)- 6 productions in lipopolysaccharide (LPS)-treated RAW 264.7 cells were
      explored by enzyme linked immunosorbent assay (ELISA) in vitro. To study wound
      healing properties of ECMS in vivo, excision and incision wound models were
      performed on rats. Inflammatory cytokines from wound biopsies such as NO, TNF
      alpha and IL-6 production were tested by ELISA. mRNA levels of iNOS,
      cyclooxygenase (COX) -2 and TNF-alpha were detected by real-time Polymerase Chain
      Reaction (PCR), and protein levels of IL-1beta and Heme Oxygenase (HO) -1 were
      analyzed by Western blotting. RESULTS: ECMS potently inhibited LPS-induced
      production of IL-6, NO and TNF-alpha in RAW 264.7 cells. The presence of
      quercetin, kaempferol, ursolic acid and gallic acid in ECMS might be responsible
      for its anti-inflammatory activity. 3% and 5% w/w ECMS significantly accelerated
      the wound healing process in both wound models, evidenced by the faster rate of
      wound contraction, epithelialization, increased hydroxyproline content, high
      tensile strength, decreased level of inflammatory markers compared to the control
      group. Histopathological studies also revealed the amelioration of wound healing
      by re-epithelialization, collagenation and vascularization of wounded skin sample
      in ECMS treated groups. CONCLUSION: The experimental data revealed that CMS had
      ability to prevent exaggerated inflammation and accelerates wound
      epithelialization and might be beneficial for healing dermal wounds.

PMID- 29567278
TI  - Antinociceptive activity of Inula britannica L. and patuletin: In vivo and
      possible mechanisms studies.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Inula britannica L. is a predominant medicinal
      plant traditionally utilized in the treatments of arthritis and back pain in
      Iranian folk medicine. AIM OF THE STUDY: The purpose of this research was to
      evaluate the antinociceptive effects of Inula britannica L. flower essential oil
      (IBLEO) and one of its major constituents, Patuletin (Pn), in male mice.
      MATERIALS AND METHODS: In this study, we used pain assessment tests including
      acetic acid-induced writhing, tail-flick (TF), formalin induced paw licking
      (FIPL) model, and glutamate-induced paw licking (GPL). For understanding the
      supposed antinociceptive mechanisms of IBLEO, opioid and L-arginine/NO/cGMP/ KATP
      pathways were examined. RESULTS: In the TF, writhing, GPL, and FIPL tests, a
      dosage of 100 mg/kg of IBLEO showed noteworthy antinociceptive effects in
      comparison with control (p < 0.05). In writhing test, administration of selective
      opioid antagonists (naltrindole, nor-binaltorphimine, and naloxonazine)
      attenuated the antinociceptive effect of IBLEO in comparison with control (p <
      0.001). Both methylene blue and glibenclamide blocked the antinociceptive effect
      of IBLEO (p < 0.05), but the administration of L-arginine or sodium nitroprusside
      fundamentally potentiated the antinociception induced by IBLEO in phase II of the
      FIPL (p < 0.05). Additionally, patuletin showed significant antinociceptive
      effects in writhing, FIPL, and GPL tests (p < 0.01). CONCLUSION: The results of
      this examination showed that IBLEO and Pn have antinociceptive effects. The
      modulation of glutamatergic systems by opioid receptors could be involved, at
      least in part, in these effects. Our data also suggest the activation of the L
      arginine/NO/cGMP/KATP pathway in IBLEO antinociceptive effects.

PMID- 29567279
TI  - [Neuroendocrine tumors of the breast: Myth or reality? A systematic review].
AB  - Primary neuroendocrine breast carcinomas are rare and little-known tumors. Only a
      limited number of studies on neuroendocrine breast carcinomas have been reported
      in the literature, and the vast majority of them are small retrospective series
      or case reports. According to the World Health Organization (WHO), they account
      for only 2 % to 5 % of breast cancers. Their diagnosis relies on the presence of
      a neuroendocrine architecture and the expression of neuroendocrine markers
      (chromogranin A and/or synaptophysin). The revised 2012 WHO classification
      subdivides them into three categories: (i) well-differentiated neuroendocrine
      carcinomas, (ii) poorly differentiated neuroendocrine carcinomas or small-cell
      carcinomas, and (iii) invasive breast carcinomas with neuroendocrine
      differentiation. Their clinical features and radiological characteristics are not
      different from those of other types of breast cancer. Because of discordant
      results, their clinical outcome is still poorly defined. So far, no standard
      treatment has been established, and most clinicians draw on their experience of
      invasive ductal cancer. The role of specific treatments like platinum-based
      chemotherapy, somatostatin analogues, peptide receptor radionucleide therapy or
      temozolomide remains unclear. A better knowledge of the molecular pathways
      involved in their carcinogenesis could help to identify new potential therapeutic
      targets. The efficacy of targeted therapies has to be studied.

PMID- 29567280
TI  - [Hepatocellular carcinoma: Increase in incidence or future plague?]
AB  - Hepatocellular carcinoma is the third most frequent cause of cancer death
      worldwide, particularly in Asia and Africa. Most cases complicate an underlying
      liver cirrhosis due to hepatitis B or C chronic virus infection or alcoholic
      abuse. But, following the current epidemics of obesity and type 2 diabetes, it
      appears that these diseases, associated in metabolic syndrome, are responsible
      for non alcoholic fatty liver disease at risk of HCC frequently before the stage
      of cirrhosis. Recent hypotheses consider that in the near future, cancer deaths
      due to HCC will overpass in USA those due to breast or colorectal cancers.
      Governments should develop policies to prevent obesity, type 2 diabetes and the
      metabolic syndrome as well as fight against alcoholism and hepatitis B and C
      virus infections.

PMID- 29567281
TI  - [Multidisciplinary oncopalliative meeting: Aims and pratical recommendations].
AB  - Progress leads to increase life duration at the metastatic stage but metastatic
      disease is most often lethal. Decision-making is necessary for an increasing
      period of care, beyond evidence-based medicine, dealing with complexity and
      uncertain benefit/risk ratio. This requires to inform the patient realistically,
      to discuss prognostication, to develop anticipated written preferences. These
      changes mean to pass from a medicine based on informed consent to medicine based
      on respect of the patient wishes even if it can be complex to determine. A new
      multidisciplinarity is needed, centered on the meaning of the care, the
      proportionality of the care, the anticipated patient trajectory. The ASCO has
      published recommendations on early palliative care. The timing and the quality of
      the discussion between palliative care specialists and oncologists is crucial. We
      propose 10 steps to organize a multidisciplinary onco-palliative meeting, as it
      appears the key for the organization of care in non-curable disease.

PMID- 29567282
TI  - Data monitoring committees and stopping trials-Giving participants a voice.

PMID- 29567284
TI  - Candida auris in contemporary mycology labs: A few practical tricks to identify
      it reliably according to one recent French experience.

PMID- 29567283
TI  - Rationale, development, and design of the Altering Intake, Managing Symptoms
      (AIMS) dietary intervention for bowel dysfunction in rectal cancer survivors.
AB  - PURPOSE: Bowel dysfunction is a common, persistent long-term effect of treatment
      for rectal cancer survivors. Survivors often use dietary modifications to
      maintain bowel control. There are few evidence-based interventions to guide
      survivors on appropriate diet modifications for bowel symptom management. The
      purpose of this paper is to describe the development and design of the Altering
      Intake, Managing Symptoms (AIMS) intervention to support bowel dysfunction
      management in rectal cancer survivors. METHODS: The AIMS intervention is a ten
      session, telephone-based diet behavior change intervention delivered by trained
      health coaches. It uses dietary recall, participant-completed food and symptom
      diaries, and health coaching guided by motivational interviewing to promote bowel
      symptom management and improved diet quality. Based on the Chronic Care Self
      Management Model (CCM), the AIMS Intervention is designed to improve self
      efficacy and self-management of bowel symptoms by coaching survivors to
      appropriately modify their diets through goal setting, self-monitoring, and
      problem-solving. The intervention targets survivors with stage I-III rectosigmoid
      colon/rectum cancer who are 6 months post-treatment, 21 years and older, and
      English-speaking. CONCLUSIONS: The design and development process described in
      this paper provides an overview and underscores the potential of the AIMS
      intervention to positively impact the quality of long-term survivorship for
      rectal cancer survivors. An ongoing pilot study will inform the design and
      development of future multi-site Phase II and III randomized trials.

PMID- 29567285
TI  - Pseudallescheria/Scedosporium complex species: From saprobic to pathogenic
      fungus.
AB  - Scedosporiosis is an emerging fungal infection caused by
      Pseudallescheria/Scedosporium complex species (PSC). This pathogen has been drawn
      significant interest in recent years due to its worldwide prevalence, the
      seriousness of its infection, associated with high mortality in both
      immunocompromised and immunocompetent hosts and its cryptic ecology, distribution
      and epidemiology across the globe. These species complexes can be found in
      environments impacted by human. The purpose of this review is to describe the
      characteristics, mode of transmission, ecology, prevalence, global epidemiology
      of this fungal group in order to increase the awareness of among clinicians and
      microbiologists, especially in regions with high endemic, as well as to promote
      further research on all of its aspects.

PMID- 29567286
TI  - Do We Really Need to Repeat Computed Tomography Imaging in Isolated Mild
      Traumatic Subarachnoid Hemorrhage?

PMID- 29567287
TI  - Surgical Management of Supratentorial Intracerebral Hemorrhages: Endoscopic
      Versus Open Surgery.
AB  - OBJECTIVE: Intracerebral hemorrhage continues to be a major global problem. No
      standard treatment or surgical procedure has been identified for intracerebral
      hemorrhages. High morbidity and mortality rates caused by conventional approaches
      and the disease itself have necessitated more-invasive treatment methods. The
      endoscopic approach is a more minimally invasive method than craniotomy, which is
      another alternative surgical treatment. METHODS: We compared intracerebral
      hematoma drainage in 2 groups of 17 patients each, treated with minimally
      invasive endoscopic method versus craniotomy. All the patients were treated for
      supratentorial spontaneous hemorrhage between December 2013 and February 2017 at
      the Neurosurgery Clinic of Ankara University Faculty of Medicine. RESULTS: We
      retrospectively evaluated 34 patients surgically treated between December 2013
      and February 2017. All patients underwent surgery within the first 24 hours.
      Patients in the early surgery group had better surgical outcomes. In the
      neuroendoscopic group, Glasgow Coma Scale increased from 6 to 11 at 1 week
      postoperatively compared with 5 to 9 in the craniotomy group. CONCLUSIONS:
      Minimally invasive endoscopic hematoma evacuation may be a good alternative
      surgical method for treating supratentorial spontaneous cerebral hematomas.

PMID- 29567288
TI  - Elitism and Populism in Science Publishing.

PMID- 29567289
TI  - Construction and Validation of Educational Material for Children with
      Hydrocephalus and Their Informal Caregivers.
AB  - OBJECTIVE: To build and validate journal-type digital and printed educational
      material for informal caregivers (i.e., the parents who provide care) of children
      with hydrocephalus. METHODS: This is a methodologic study conducted in the
      children's neurosurgery outpatient clinic of a university hospital. The content
      validity index with a concordance of >=0.78 was used for validation. Content was
      validated with the participation of 5 nurses and 3 neurosurgeons, and appearance
      was validated with the participation of 9 informal caregivers of children with
      hydrocephalus. RESULTS: A 21-page journal was created to address hydrocephalus
      and its treatment. The content and semantics of this material were validated with
      a universal content validity index of 0.90 and 0.98, respectively. CONCLUSIONS:
      Content and appearance of the educational material for informal caregivers of
      children with hydrocephalus were successfully validated and considered suitable
      and user-friendly for health education.

PMID- 29567290
TI  - Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in
      Patients with Spinal Cord Injury.
AB  - BACKGROUND: Osteoporosis is one of the most common problems of patients with
      spinal cord injuries (SCIs). The current study aimed to evaluate the
      antiosteoporotic effects of curcumin on densitometry parameters and biomarkers of
      bone turnovers among patients with SCI. MATERIALS AND METHODS: The current
      controlled clinical trial was conducted among 100 patients with SCI referred to
      an outpatient clinic of rehabilitation in Ilam City, Iran, in 2013-2015. The
      intervention group received 110/mg/kg/day curcumin for 6 months and the control
      group received placebo. Bone mineral density (BMD) was measured in all patients.
      The level of procollagen type I N-terminal propeptide, serum carboxy-terminal
      telopeptide of type I collagen, osteocalcin, and bone-specific alkaline
      phosphates were compared before and after study. RESULTS: BMD indicators of
      lumbar, femoral neck, and total hip in the control group significantly decreased
      compared with the beginning of study. However, in the curcumin group, a
      significant increase was observed in BMD indicators of lumbar, femoral neck, and
      hip at the end of study compared with the beginning. There was also a significant
      difference between interventional and control groups for the mean BMD of femoral
      neck and hip at the end of study (0.718 +/- 0.002 g/cm2 vs. 0.712 +/- 0.003 g/cm2
      and 0.742 +/- 0.031 g/cm2 vs. 0.692 +/- 0.016 g/cm2, respectively). CONCLUSIONS:
      Curcumin, via modulation of densitometry indices and bone resorption markers,
      showed inhibitory effects on the process of osteoporosis. Treatment with curcumin
      was significantly associated with a decrease in the osteoporosis progression and
      bone turnover markers of patients with SCI after 6 months.

PMID- 29567292
TI  - N-terminome and proteogenomic analysis of the Methylobacterium extorquens DM4
      reference strain for dichloromethane utilization.
AB  - : Methylobacterium strains can use one-carbon compounds, such as methanol, for
      methylotrophic growth. In addition to methanol, a few strains also utilize
      dichloromethane, a major industrial chlorinated solvent pollutant. With a fully
      assembled and annotated genome, M. extorquens DM4 is the reference bacterium for
      aerobic dichloromethane degradation. The doublet N-terminal oriented proteomics
      (dN-TOP) strategy was applied to further improve its genome annotation and a
      differential proteomics approach was performed to compare M. extorquens DM4 grown
      either with methanol or dichloromethane as the sole source of carbon and energy.
      These approaches led to experimental confirmation of 259 hypothetical proteins,
      correction of 78 erroneous predicted start codons, discovery of 39 new proteins
      and annotation of 66 signal peptides, including essential enzymes involved in
      methylotrophic growth. SIGNIFICANCE: Dichloromethane (methylene chloride, CH2Cl2,
      DCM) is one of the most widely used industrial halogenated solvents and a
      potential carcinogen. Microbial rehabilitation of worldwide-contaminated sites
      involves DCM breakdown by bacteria that are able to grow using this pollutant as
      their sole carbon and energy source. The most-studied methylotrophic DCM degrader
      is Methylobacterium extorquens strain DM4. Proteomic studies of the
      Methylobacterium genus have been performed previously, but genome-wide
      investigation of N-termini of expressed proteins has not yet been performed.
      Differential quantitative proteomic analysis also opens new research perspectives
      to better monitor and understand bacterial growth with DCM.

PMID- 29567291
TI  - Computed Tomography Angiography Evaluation of Risk Factors for Unstable
      Intracranial Aneurysms.
AB  - OBJECTIVE: To evaluate risk factors for instability in intracranial aneurysms
      (IAs) using computed tomography angiography (CTA). METHODS: A total of 614
      consecutive patients diagnosed with 661 IAs between August 2011 and February 2016
      were reviewed. Patients and IAs were divided into stable and unstable groups.
      Along with clinical characteristics, IA characteristics were evaluated by CTA.
      Multiple logistic regression analysis was used to identify the independent risk
      factors associated with unstable IAs. Receiver operating characteristic (ROC)
      curve analysis was performed on the final model, and optimal thresholds were
      obtained. RESULTS: Patient age (odds ratio [OR], 0.946), cerebral atherosclerosis
      (CA; OR, 0.525), and IAs located at the middle cerebral artery (OR, 0.473) or
      internal carotid artery (OR, 0.512) were negatively correlated with instability,
      whereas IAs with irregular shape (OR, 2.157), deep depth (OR, 1.557), or large
      flow angle (FA; OR, 1.015) were more likely to be unstable. ROC analysis revealed
      threshold values of age, depth, and FA of 59.5 years, 4.25 mm, and 87.8 degrees ,
      respectively. CONCLUSIONS: The stability of IAs is significantly affected by
      several factors, including patient age and the presence of CA. IA shape and
      location also have an impact on the stability of IAs. Growth into an irregular
      shape, with a deep depth, and a large FA are risk factors for a change in IAs
      from stable to unstable.

PMID- 29567293
TI  - How nitrogen sources influence Mortierella alpina aging: From the lipid droplet
      proteome to the whole-cell proteome and metabolome.
AB  - : Arachidonic acid (ARA) is a valuable polyunsaturated fatty acid produced by
      Mortierella alpina. Although some strategies such as nitrogen supplementation
      have shown the potential to affect the aging of M. alpina in ways which enable it
      to produce more ARA, the underlying mechanism remains elusive. Herein, we
      conducted a systematical analysis of the lipid droplet proteome, as well as the
      whole-cell proteome and metabolome, in order to elucidate how and why two
      different nitrogen sources (KNO3 and urea) affect the aging of M. alpina and the
      corresponding ARA concentration. We found that KNO3 promoted the ARA
      concentration, while urea accelerated lipid consumption and stimulated the
      decomposition of mycelia. Although both KNO3 and urea activated carbohydrate
      metabolic pathways, KNO3 exerted a stronger promoting effect on the pentose
      phosphate pathway and induced the lipid droplets to participate in the citrate
      pyruvate cycle. The activities of malic enzyme and isocitrate dehydrogenase were
      also promoted more by KNO3. These pathways provided additional substrates and
      reducing power for ARA synthesis and ROS elimination. Accordingly, since urea
      showed a weaker promotion of the related pathways, it caused a depression of the
      antioxidant system and a consequent increase of ROS. These findings facilitate
      the design of nitrogen supplementation strategies to achieve higher ARA
      concentrations, and provide guidance for deciphering the mechanisms of similar
      aging phenomena in other oleaginous microorganisms. SIGNIFICANCE: Polyunsaturated
      fatty acids such as arachidonic acid (ARA) are valuable nutrients, which play
      important roles in preventing numerous diseases and facilitating development.
      Although it has been found for years that ARA production will be increased in the
      aging process of Mortierella alpina (M. alpina) and nitrogen sources are involved
      in this process, the underlying mechanism for this phenomenon remains unknown. In
      this work, we used the subcellular proteomics, whole-cell proteomics and
      metabolomics methods to explore the mechanisms by which two different nitrogen
      (KNO3 and urea) affected the aging process of M. alpina. Finally, we gave some
      new insights for the mechanisms mentioned above. This finding will fuel the
      technology developments for the ARA production using microbes.

PMID- 29567294
TI  - A meta-analysis and systematic literature review of factors associated with
      sexual risk-taking during international travel.
AB  - BACKGROUND: International travel facilitates global spread of sexually
      transmitted infections (STI). Travellers could contribute to onward transmission
      of pathogens rarely encountered at home and export new strains to the
      destination. The aim was to systematically examine evidence regarding
      determinants of travel-related sexual risk-taking and identify knowledge gaps and
      areas for targeted interventions. METHOD: Articles published in peer-reviewed
      journals from 2000 to 2017 were screened in 6 databases and assessed for
      relevance against criteria. Data was extracted for factors associated with travel
      related STI or proxies. Meta-analyses estimated pooled prevalence of casual sex
      and non-condom use. Adjusted odds ratios of predictors were pooled to generate a
      combined estimate. RESULT: Forty-nine articles qualified for inclusion. A
      heterogeneity test indicated variation across studies. The pooled prevalence of
      casual travel sex was 35% and prevalence of non-condom use 17%. Expectations of
      casual sex strongly predicted sex with a new partner when travelling abroad.
      Planning to have sex indicated condom use. CONCLUSION: The studies largely
      represented sub-groups of risk-taking populations from a European context,
      indicating substantial knowledge gaps. Studies investigating migrants travelling
      to visit friends and relatives, older travellers, and female travelers are
      needed. Post-travel harm reduction activities may serve as a focus for future
      interventions.

PMID- 29567295
TI  - Design, synthesis and biological evaluation of novel 3-substituted
      pyrazolopyrimidine derivatives as potent Bruton's tyrosine kinase (BTK)
      inhibitors.
AB  - A series of 3-substituted pyrazolopyrimidine derivatives as BTK inhibitors were
      designed by structure-based drug design and they were synthesized, evaluated by
      enzyme-based assay and anti-proliferation against Ramos and Raji cells. Most of
      them displayed good inhibitory activities against both BTK and B-cell
      lymphoblastic leukemia lines in vitro. Among them, compound 8a exhibited
      excellent potency (IC50 = 7.95 nM against BTK enzyme, 8.91 MUM against Ramos
      cells and 1.80 MUM against Raji cells), with a better hydrophilicity (ClogP =
      3.33). These explorations provided new clues to discover 3-substituted
      pyrazolopyrimidine derivatives as novel anti-tumor agents.

PMID- 29567296
TI  - Discovery of a novel allosteric inhibitor scaffold for polyadenosine-diphosphate
      ribose polymerase 14 (PARP14) macrodomain 2.
AB  - The polyadenosine-diphosphate-ribose polymerase 14 (PARP14) has been implicated
      in DNA damage response pathways for homologous recombination. PARP14 contains
      three (ADP ribose binding) macrodomains (MD) whose exact contribution to overall
      PARP14 function in pathology remains unclear. A medium throughput screen led to
      the identification of N-(2(-9H-carbazol-1-yl)phenyl)acetamide (GeA-69, 1) as a
      novel allosteric PARP14 MD2 (second MD of PARP14) inhibitor. We herein report
      medicinal chemistry around this novel chemotype to afford a sub-micromolar PARP14
      MD2 inhibitor. This chemical series provides a novel starting point for further
      development of PARP14 chemical probes.

PMID- 29567297
TI  - Fine-tuning the physicochemical properties of peptide-based blood-brain barrier
      shuttles.
AB  - N-methylation is a powerful method to modify the physicochemical properties of
      peptides. We previously found that a fully N-methylated tetrapeptide, Ac-(N
      MePhe)4-CONH2, was more lipophilic than its non-methylated analog Ac-(Phe)4
      CONH2. In addition, the former crossed artificial and cell membranes while the
      latter did not. Here we sought to optimize the physicochemical properties of
      peptides and address how the number and position of N-methylated amino acids
      affect these properties. To this end, 15 analogs of Ac-(Phe)4-CONH2 were designed
      and synthesized in solid-phase. The solubility of the peptides in water and their
      lipophilicity, as measured by ultra performance liquid chromatography (UPLC)
      retention times, were determined. To study the permeability of the peptides, the
      Parallel Artificial Membrane Permeability Assay (PAMPA) was used as an in vitro
      model of the blood-brain barrier (BBB). Contrary to the parent peptide, the 15
      analogs crossed the artificial membrane, thereby showing that N-methylation
      improved permeability. We also found that N-methylation enhanced lipophilicity
      but decreased the water solubility of peptides. Our results showed that both the
      number and position of N-methylated residues are important factors governing the
      physicochemical properties of peptides. There was no correlation between the
      number of N-methylated amide bonds and any of the properties measured. However,
      for the peptides consecutively N-methylated from the N-terminus to the C-terminus
      (p1, p5, p11, p12 and p16), lipophilicity correlated well with the number of N
      methylated amide bonds and the permeability of the peptides. Moreover, the
      peptides were non-toxic to HEK293T cells, as determined by the 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      (MTS) assay.

PMID- 29567298
TI  - Associations between Gut Microbiota and Common Luminal Intestinal Parasites.
AB  - The development and integration of DNA-based methods in research and clinical
      microbiology laboratories have enabled standardised and comprehensive detection
      and differentiation of the microbes colonising our guts. For instance, the single
      celled parasites Blastocystis and Dientamoeba appear to be much more common than
      previously thought, especially so in healthy individuals. While increasing
      evidence appears to suggest limited pathogenicity of these parasites, next
      generation-sequencing-based studies have helped us to appreciate links between
      parasite colonisation and certain host phenotypical characteristics and gut
      microbial profiles. The fundamental question remains as to whether such parasites
      are merely indicators or active manipulators of gut microbiota structure and
      function. In this article, we collate existing evidence that these parasites are,
      at minimum, indicators of intestinal microbiota structure.

PMID- 29567299
TI  - Association Between Self-reported Physical Activity and Skin Autofluorescence, a
      Marker of Tissue Accumulation of Advanced Glycation End Products in Adults With
      Type 1 Diabetes: A Cross-sectional Study.
AB  - PURPOSE: The accumulation of advanced glycation end products (AGEs) in local
      tissue is an important cause of low-grade inflammation and oxidative stress and
      is linked to late diabetic complications. Physical activity has various
      beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated
      with lower frequency of chronic complications of diabetes, although the specific
      mechanisms still remain unclear. The present study determines the association
      between self-reported physical activity and skin autofluorescence (AF), a marker
      of tissue accumulation of AGEs in adults with T1D. METHODS: We enrolled 119
      patients (63 women), aged 34 years (interquartile range [IQR], 26-41 years), with
      T1D duration of 17 years (IQR, 12-25 years), glycosylated hemoglobin (HbA1c) of
      7.9% (IQR, 7.1%-8.9%) referred to an outpatient diabetes clinic. Patients with
      diabetes duration of <5 years, age >65 years, concomitant diabetic ketoacidosis,
      and severe complications that restrict physical activity (eg, diabetic foot,
      diabetic proliferative retinopathy, blindness) were excluded. Physical activity
      was measured with the short version of the International Physical Activity
      Questionnaire (IPAQ-SF), and raw scores were then log-transformed because of non
      normality. The accumulation of AGEs in the skin was assessed on the basis of skin
      AF. Correlations between AF and various laboratory and clinical findings were
      assessed, and multivariate linear regression analysis was used to examine factors
      that influenced AGEs. FINDINGS: Skin AF correlated positively with age
      (Spearman's coefficient [Rs] = 0.47; P < 0.0001), HbA1c (Rs = 0.30; P = 0.001),
      waist-to-hip ratio (WHR; Rs = 0.23; P = 0.02), and negatively with logIPAQ-SF (Rs
      = -0.28; P = 0.002). A stepwise multivariable linear regression analysis
      indicated age (beta = 0.46; P < 0.0001), HbA1c (beta = 0.21; P = 0.01), and
      logIPAQ-SF score (beta = -0.17; P = 0.04) as predictors of the skin AF after
      adjustment for sex and WHR (R2 = 0.36; P < 0.0001). IMPLICATIONS: Higher physical
      activity is related to lower accumulation of AGEs in patients with T1D. Our study
      provides new insight into the beneficial effects of physical activity in T1D
      according to tissue accumulation of AGEs.

PMID- 29567300
TI  - Fetal Sex, Need for Insulin, and Perinatal Outcomes in Gestational Diabetes
      Mellitus: An Observational Cohort Study.
AB  - PURPOSE: This was a prospective observational cohort study that aimed to
      determine whether fetal sex influences the maternal and fetal outcomes of
      gestational diabetes mellitus (GDM). METHODS: In this study, 327 European
      primiparous women were consecutively recruited after diagnosis of GDM. AUC on the
      oral glucose tolerance test (OGTT), need for insulin therapy, maternal and
      obstetrical outcomes, and fetal fat mass (by measuring the thickness of the
      anterior abdominal subcutaneous tissue) were recorded and compared between the
      two subgroups of female and male fetuses. FINDINGS: Despite the absence of
      differences in multiple comparisons of the OGTT, the AUC-OGTT was significantly
      higher in women carrying a male fetus (22.6 [3.2] mmol/L vs 19.7 [2.8] mmol/L).
      The abdominal fat thickness appeared to increase with gestational age, with
      higher growth in male fetuses than in female fetuses. The overall risk of need
      for insulin therapy was significantly higher in women carrying a male fetus (odds
      ratio = 1.837). At delivery, birthweight was higher in males than in females only
      if adjusted for gestational age, similarly for placental weight, otherwise there
      were no significant differences between the groups in total length of gestation,
      rates of cesarean delivery, and Apgar scores. IMPLICATIONS: Overall, our data
      propose an association between fetal sex and GDM outcomes, suggesting the
      hypothesis that in maternal-fetal interactions, the fetus can affect maternal
      glucose metabolism.

PMID- 29567301
TI  - Corrigendum to "Pharmacotherapy for NASH: Current and emerging" [J Hepatol 68
      (2017) 362-375].

PMID- 29567302
TI  - Synthesis and characterization of CoOx/BiVO4 photocatalysts for the degradation
      of propyl paraben.
AB  - Cobalt-promoted bismuth vanadate photocatalysts of variable cobalt content (0-1.0
      wt.%) were synthesized and characterized with various techniques including BET,
      XRD, DRS, XPS and TEM. BiVO4 exists in the monoclinic scheelite structure, while
      cobalt addition improves the absorbance in the visible region although it does
      not affect the band gap energy of BiVO4. Cobalt exists in the form of well
      dispersed Co3O4 nanocrystallites, which are in intimate contact with the much
      larger BiVO4 nanoparticles. Photocatalytic activity was evaluated for the
      degradation of propyl paraben (PP) under simulated solar radiation. The activity
      of pristine BiVO4 is significantly improved adding small amounts of cobalt and is
      maximized for the catalyst containing 0.5 wt.% Co. PP degradation in ultrapure
      pure water increases with increasing photocatalyst loading (100 mg/L to 1.5 g/L),
      and decreasing PP concentration (1600-200 MUg/L). Experiments in bottled water,
      as well as in pure water spiked with bicarbonate and chloride ions showed little
      effect of non-target inorganics on degradation. Conversely, degradation is
      severely impeded in secondary treated wastewater. The enhancement of the
      photocatalytic activity of the synthesized catalysts is attributed to efficient
      electron-hole separation, achieved at the p-n junction formed between the p-type
      Co3O4 and the n-type BiVO4 semiconductors.

PMID- 29567303
TI  - Photo-Fenton treatment of saccharin in a solar pilot compound parabolic
      collector: Use of olive mill wastewater as iron chelating agent, preliminary
      results.
AB  - The aim of this work was to investigate the treatment of the artificial sweetener
      saccharin (SAC) in a solar compound parabolic collector pilot plant by means of
      the photo-Fenton process at pH 2.8. Olive mill wastewater (OMW) was used as iron
      chelating agent to avoid acidification of water at pH 2.8. For comparative
      purposes, Ethylenediamine-N, N-disuccinic acid (EDDS), a well-studied iron
      chelator, was also employed at circumneutral pH. Degradation products formed
      along treatment were identified by LC-QTOF-MS analysis. Their degradation was
      associated with toxicity removal, evaluated by monitoring changes in the
      bioluminescence of Vibrio fischeri bacteria. Results showed that conventional
      photo-Fenton at pH 2.8 could easily degrade SAC and its intermediates yielding k,
      apparent reaction rate constant, in the range of 0.64-0.82 L kJ-1, as well as,
      eliminate effluent's chronic toxicity. Both OMW and EDDS formed iron-complexes
      able to catalyse H2O2 decomposition and generate HO. OMW yielded lower SAC
      oxidation rates (k = 0.05-0.1 L kJ-1) than EDDS (k = 2.21-7.88 L kJ-1) possibly
      due to its higher TOC contribution. However, the degradation rates were improved
      (k = 0.13 L kJ-1) by increasing OMW dilution in the reactant mixture. All in all,
      encouraging results were obtained by using OMW as iron chelating agent, thus
      rendering this approach promising towards the increase of process sustainability.

PMID- 29567304
TI  - First description of novel arginine catabolic mobile elements (ACMEs) types IV
      and V harboring a kdp operon in Staphylococcus epidermidis characterized by whole
      genome sequencing.
AB  - The arginine catabolic mobile element (ACME) was first described in the
      methicillin-resistant Staphylococcus aureus strain USA300 and is thought to
      facilitate survival on skin. To date three distinct ACME types have been
      characterized comprehensively in S. aureus and/or Staphylococcus epidermidis.
      Type I harbors the arc and opp3 operons encoding an arginine deaminase pathway
      and an oligopeptide permease ABC transporter, respectively, type II harbors the
      arc operon only, and type III harbors the opp3 operon only. To investigate the
      diversity and detailed genetic organization of ACME, whole genome sequencing
      (WGS) was performed on 32 ACME-harboring oro-nasal S. epidermidis isolates using
      MiSeq- and PacBio-based WGS platforms. In nine isolates the ACMEs lacked the opp3
      operon, but harbored a complete kdp operon (kdpE/D/A/B/C) located a maximum of
      2.8 kb upstream of the arc operon. The kdp operon exhibited 63% DNA sequence
      identity to the native S. aureus kdp operon. These findings identified a novel,
      previously undescribed ACME type (designated ACME IV), which could be subtyped
      (IVa and IVb) based on distinct 5' flanking direct repeat sequences (DRs).
      Multilocus sequence typing (MLST) sequences extracted from the WGS data
      identified the sequence types (STs) of the isolates investigated. Four of the
      nine ACME IV isolates belonged to ST153, and one to ST17, a single locus variant
      of ST153. A tenth isolate, identified as ST5, harbored another novel ACME type
      (designated ACME V) containing the kdp, arc and opp3 operons and flanked by DR_F,
      and DR_B but lacked any internal DRs. ACME V was colocated with a staphylococcal
      chromosome cassette mec (SCCmec) IV element and Clustered Regularly Interspaced
      Short Palindromic Repeats (CRISPR) in a 116.9 kb composite island. The extensive
      genetic diversity of ACME in S. epidermidis has been further elucidated by WGS,
      revealing two novel ACME types IV and V for the first time.

PMID- 29567305
TI  - Novel SCCmec type XIII (9A) identified in an ST152 methicillin-resistant
      Staphylococcus aureus.
AB  - We identified a novel staphylococcal cassette chromosome mec (SCCmec) element in
      an ST152 methicillin-resistant Staphylococcus aureus (MRSA) isolate by combining
      Illumina and MinION sequencing. The element contains a new ccrC allotype
      designated ccrC2. The mec complex resembles mec class A, but with an altered
      organization of the genes. The element was acknowledged as novel by the
      International Working Group on the Classification of Staphylococcal Cassette
      Chromosome Elements (IWG-SCC) and designated SCCmec type XIII (9A).

PMID- 29567306
TI  - Reliability and comparison of Kinect-based methods for estimating spatiotemporal
      gait parameters of healthy and post-stroke individuals.
AB  - Different studies have analyzed the potential of the off-the-shelf Microsoft
      Kinect, in its different versions, to estimate spatiotemporal gait parameters as
      a portable markerless low-cost alternative to laboratory grade systems. However,
      variability in populations, measures, and methodologies prevents accurate
      comparison of the results. The objective of this study was to determine and
      compare the reliability of the existing Kinect-based methods to estimate
      spatiotemporal gait parameters in healthy and post-stroke adults. Forty-five
      healthy individuals and thirty-eight stroke survivors participated in this study.
      Participants walked five meters at a comfortable speed and their spatiotemporal
      gait parameters were estimated from the data retrieved by a Kinect v2, using the
      most common methods in the literature, and by visual inspection of the videotaped
      performance. Errors between both estimations were computed. For both healthy and
      post-stroke participants, highest accuracy was obtained when using the speed of
      the ankles to estimate gait speed (3.6-5.5 cm/s), stride length (2.5-5.5 cm), and
      stride time (about 45 ms), and when using the distance between the sacrum and the
      ankles and toes to estimate double support time (about 65 ms) and swing time (60
      90 ms). Although the accuracy of these methods is limited, these measures could
      occasionally complement traditional tools.

PMID- 29567307
TI  - Development and validation of a subject-specific moving-axis tibiofemoral joint
      model using MRI and EOS imaging during a quasi-static lunge.
AB  - The aims of this study were to introduce and validate a novel computationally
      efficient subject-specific tibiofemoral joint model. Subjects performed a quasi
      static lunge while micro-dose radiation bi-planar X-rays (EOS Imaging, Paris,
      France) were captured at roughly 0 degrees , 20 degrees , 45 degrees , 60 degrees
      , and 90 degrees  of tibiofemoral flexion. Joint translations and rotations were
      extracted from this experimental data through 2D-to-3D bone reconstructions,
      using an iterative closest point optimization technique, and employed during
      model calibration and validation. Subject-specific moving-axis and hinge models
      for comparisons were constructed in the AnyBody Modeling System (AMS) from
      Magnetic Resonance Imaging (MRI)-extracted anatomical surfaces and compared
      against the experimental data. The tibiofemoral axis of the hinge model was
      defined between the epicondyles while the moving-axis model was defined based on
      two tibiofemoral flexion angles (0 degrees  and 90 degrees ) and the articulation
      modeled such that the tibiofemoral joint axis moved linearly between these two
      positions as a function of the tibiofemoral flexion. Outside this range, the
      joint axis was assumed to remain stationary. Overall, the secondary joint
      kinematics (ML: medial-lateral, AP: anterior-posterior, SI: superior-inferior,
      IE: internal-external, AA: adduction-abduction) were better approximated by the
      moving-axis model with mean differences and standard errors of (ML: -1.98 +/-
      0.37 mm, AP: 6.50 +/- 0.82 mm, SI: 0.05 +/- 0.20 mm, IE: 0.59 +/- 0.36 degrees ,
      AA: 1.90 +/- 0.79 degrees ) and higher coefficients of determination (R2) for
      each clinical measure. While the hinge model achieved mean differences and
      standard errors of (ML: -0.84 +/- 0.45 mm, AP: 10.11 +/- 0.88 mm, SI: 0.66 +/-
      0.62 mm, IE: -3.17 +/- 0.86 degrees , AA: 11.60 +/- 1.51 degrees ).

PMID- 29567308
TI  - Ventricular flow dynamics with varying LVAD inflow cannula lengths: In-silico
      evaluation in a multiscale model.
AB  - Left ventricular assist devices are associated with thromboembolic events, which
      are potentially caused by altered intraventricular flow. Due to patient
      variability, differences in apical wall thickness affects cannula insertion
      lengths, potentially promoting unfavourable intraventricular flow patterns which
      are thought to be correlated to the risk of thrombosis. This study aimed to
      present a 3D multiscale computational fluid dynamic model of the left ventricle
      (LV) developed using a commercial software, Ansys, and evaluate the risk of
      thrombosis with varying inflow cannula insertion lengths in a severely dilated
      LV. Based on a HeartWare HVAD inflow cannula, insertion lengths of 5, 19, 24 and
      50 mm represented cases of apical hypertrophy, typical ranges of apical
      thicknesses and an experimental length, respectively. The risk of thrombosis was
      evaluated based on blood washout, residence time, instantaneous blood stagnation
      and a pulsatility index. By introducing fresh blood to displace pre-existing
      blood in the LV, after 5 cardiac cycles, 46.7%, 45.7%, 45.1% and 41.8% of pre
      existing blood remained for insertion lengths of 5, 19, 24 and 50 mm,
      respectively. Compared to the 50 mm insertion, blood residence time was at least
      9%, 7% and 6% higher with the 5, 19 and 24 mm insertion lengths, respectively. No
      instantaneous stagnation at the apex was observed directly after the E-wave.
      Pulsatility indices adjacent to the cannula increased with shorter insertion
      lengths. For the specific scenario studied, a longer insertion length, relative
      to LV size, may be advantageous to minimise thrombosis by increasing LV washout
      and reducing blood residence time.

PMID- 29567309
TI  - Why National Biomechanics Day?
AB  - National Biomechanics Day (NBD) seeks to expand the influence and impact of
      Biomechanics on our society by expanding the awareness of Biomechanics among
      young people. NBD will manifest this goal through worldwide, synchronized and
      coordinated celebrations and demonstrations of all things Biomechanics with high
      school students. NBD invites all Biomechanists to participate in NBD 2018,
      http://nationalbiomechanicsday.asbweb.org/.

PMID- 29567310
TI  - Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a 131I
      Labeled Polydopamine Multifunctional Nanocarrier.
AB  - Development of biocompatible nanomaterials with multiple functionalities for
      combination of radiotherapy and chemotherapy has attracted tremendous attention
      in cancer treatment. Herein, poly(ethylene glycol) (PEG) modified polydopamine
      (PDA) nanoparticles were successfully developed as a favorable biocompatible
      nanoplatform for co-loading antitumor drugs and radionuclides to achieve imaging
      guided combined radio-chemotherapy. It is demonstrated that PEGylated PDA
      nanoparticles can effectively load two different drugs including sanguinarine
      (SAN) and metformin (MET), as well as radionuclides 131I in one system. The
      loaded SAN and MET could inhibit tumor growth via inducing cell apoptosis and
      relieving tumor hypoxia, while labeling PDA-PEG with 131I enables in vivo
      radionuclide imaging and radioisotope therapy. As revealed by the therapeutic
      efficacy both in cell and animal levels, the multifunctional PDA nanoparticles
      (131I-PDA-PEG-SAN-MET) can effectively repress the growth of cancer cells in a
      synergistic manner without significant toxic side effects, exhibiting superior
      treatment outcome than the respective monotherapy. Therefore, this study provides
      a promising polymer-based platform to realize imaging-guided
      radioisotope/chemotherapy combination cancer treatment in future clinical
      application.

PMID- 29567311
TI  - Conditional Regulation of Gene Expression by Ligand-Induced Occlusion of a
      MicroRNA Target Sequence.
AB  - RNA switches that modulate gene expression with small molecules have a number of
      scientific and clinical applications. Here, we describe a novel class of small
      regulatory on switches based on the ability of a ligand-bound aptamer to promote
      stem formation between a microRNA target sequence (miR-T) and a complementary
      competing strand. Two on switch architectures employing this basic concept were
      evaluated, differing in the location of a tetracycline aptamer and the region of
      a miR-21 target sequence (miR-21-T) masked by its competing strand. Further
      optimizations of miR-21-T and its competing strand resulted in tetracycline
      regulated on switches that induced luciferase expression by 19-fold in HeLa
      cells. A similar switch design based on miR-122-T afforded 7-fold regulation when
      placed in tandem, indicating that this approach can be extended to additional miR
      T. Optimized on switches introduced into adeno-associated virus (AAV) vectors
      afforded 10-fold regulation of two antiviral proteins in AAV-transduced cells.
      Our data demonstrate that small-molecule-induced occlusion of a miR-T can be used
      to conditionally regulate gene expression in mammalian cells and suggest that
      regulatory switches built on this principle can be used to dose expression of an
      AAV transgene.

PMID- 29567312
TI  - Preclinical Strategies to Identify Off-Target Toxicity of High-Affinity TCRs.
AB  - Adoptive transfer of T cells engineered with a cancer-specific T cell receptor
      (TCR) has demonstrated clinical benefit. However, the risk for off-target
      toxicity of TCRs remains a concern. Here, we examined the cross-reactive profile
      of T cell clone (7B5) with a high functional sensitivity for the hematopoietic
      restricted minor histocompatibility antigen HA-2 in the context of HLA-A*02:01.
      HA-2pos Epstein-Barr virus-transformed B lymphoblastic cell lines (EBV-LCLs) and
      primary acute myeloid leukemia samples, but not hematopoietic HA-2neg samples,
      are effectively recognized. However, we found unexpected off-target recognition
      of human fibroblasts and keratinocytes not expressing the HA-2 antigen. To
      uncover the origin of this off-target recognition, we performed an alanine
      scanning approach, identifying six out of nine positions to be important for
      peptide recognition. This indicates a low risk for broad cross-reactivity.
      However, using a combinatorial peptide library scanning approach, we identified a
      CDH13-derived peptide activating the 7B5 T cell clone. This was confirmed by
      recognition of CDH13-transduced EBV-LCLs and cell subsets endogenously expressing
      CDH13, such as proximal tubular epithelial cells. As such, we recommend the use
      of a combinatorial peptide library scan followed by screening against additional
      cell subsets to validate TCR specificity and detect off-target toxicity due to
      cross-reactivity directed against unrelated peptides before selecting candidate
      TCRs for clinical testing.

PMID- 29567313
TI  - Keep Quiet and Stay in Line! Smart Polymers to Keep an Eye on Pancreatic Tumors.

PMID- 29567314
TI  - Sunlight-induced genotoxicity and damage in keratin structures decrease tadpole
      performance.
AB  - The increased incidence of solar ultraviolet (UV) radiation, an environmental
      genotoxic agent, due to ozone depletion or deforestation may help to explain the
      enigmatic decline of amphibian populations in specific localities. In this work,
      we evaluated the importance of DNA repair performed by photolyases to maintain
      the performance of treefrog tadpoles after acute and chronic treatments with
      environmental-simulated doses of solar UVB and UVA radiation. Immediately after
      UV treatments, tadpoles were exposed to a visible light source to activate
      photolyases or kept in dark containers. The biological effects of UV treatments
      were evaluated through morphological, histological, locomotor and survival
      analyzes of Boana pulchella tadpoles (Anura: Hylidae). The results indicate that
      tadpole body weight suffered influence after both UVB and UVA treatments,
      although the body length was bit affected. The locomotor performance of UVB
      exposed tadpoles was significantly reduced. In addition, UVB radiation induced a
      severe impact on tadpole skin, as well as on keratinized structures of mouth
      (tooth rows and jaw), indicating that these should be important effects of solar
      UV radiation in the reduction of tadpole performance. Furthermore, photolyases
      activation was fundamental for the maintenance of tadpole performance after
      chronic UVB exposures, but it was relatively inefficient after acute exposures to
      UVB, but not to UVA radiation. Therefore, this work demonstrates how the UV
      induced genotoxicity and structural alterations in the skin and oral apparatus
      affect tadpole performance and survival.

PMID- 29567315
TI  - A suppository kit for metronomic photodynamic therapy: The elimination of rectal
      cancer in situ.
AB  - : Metronomic photodynamic therapy (mPDT) was developed to improve tumor-specific
      responses through cell death by apoptosis. We developed an mPDT suppository kit
      including ALA and LED suppositories and analyzed its killing effect on rectal
      tumors in rabbits. METHODS: The ALA (10 wt%) suppository was prepared using ALA
      powder, type 36 semi-synthetic fatty acid glyceride, and azone. The LED
      suppository was constructed by encapsulating LED units and a circuit in
      transparent epoxy resin. VX2 cells were injected into the rectal submucosa of
      rabbits to establish a carcinoma model in situ. The ALA suppository was inserted
      into the rectal cavity for 30 min of uptake and activated for 1 h by the LED
      suppository at a power density of 20 mW/cm2. The mPDT process was repeated three
      times once a day. MRI was used to monitor tumor growth, histopathology and TUNEL
      staining were performed at 14 days after mPDT. RESULTS: The overall response rate
      was 60% in the mPDT group using the kit in which the tumor size was decreased up
      to about 50% at 7 days post-mPDT and almost eliminated at 14 days. HE staining
      showed that only 6.16% of the tumor tissue remained after mPDT treatment. TUNEL
      detection showed that the apoptosis rate was 18.9%. CONCLUSION: We verified the
      killing effect of the mPDT suppository kit on rectal tumors in rabbits based on
      mPDT that induced tumor cell apoptosis.

PMID- 29567316
TI  - Evaluation of membrane fluidity of multidrug-resistant isolates of Escherichia
      coli and Staphylococcus aureus in presence and absence of antibiotics.
AB  - In the face of the serious problem of antimicrobial resistance and the global
      dissemination of multidrug-resistant (MDR) bacteria, it is relevant to deeply
      study such bacteria both genetically and phenotypically. It is well known that
      bacteria have the ability to modify the biophysical properties of their
      cytoplasmic membranes, namely fluidity, in order to survive and thrive in hostile
      environments. The aim of this study was to assess and compare the membrane
      fluidity among multidrug-resistant (MDR) isolates of Escherichia coli and
      Staphylococcus aureus in absence and in presence of antibiotics (ceftazidime or
      ciprofloxacin). The membrane fluidity was monitored at 24-h intervals up to three
      days and at the sixth day, by measuring the anisotropy of 1,6-diphenyl-1,3,5
      hexatriene (DPH) and the generalized polarization (GP) of Laurdan (6-dodecanoyl-2
      dimethylaminonaphthalene). The anisotropy values as well as the Laurdan
      excitation GP (GPexc) values obtained from all three E. coli strains (two MDR
      isolates and one susceptible reference strain) were quite similar and indicative
      of a very alike membrane phospholipid composition, regardless harboring or not
      resistance to multiple antimicrobials. Nonetheless, in the case of S. aureus, the
      anisotropy values were more increased in methicillin-resistant S. aureus (MRSA)
      isolates in comparison to the reference strain, meaning they have a less fluid
      membrane. Equally, GPexc values were statistically different among the three S.
      aureus strains and showed that the two MRSA isolates had more rigid membranes
      than the susceptible strain. The exposition of MDR isolates of S. aureus to
      subinhibitory concentrations of ciprofloxacin did not affect neither the
      anisotropy values nor the GPexc values, therefore, not altering membrane
      fluidity. Membrane integrity, assessed by the Live/Dead staining, of all strains
      and conditions studied was maintained over the six days. Thus, these preliminary
      studies on membrane properties of MDR isolates demonstrate that i) MRSA seem to
      have a more rigid membrane that susceptible S. aureus and ii) the presence of
      subinhibitory concentrations of antibiotics does not significantly alter the
      membrane fluidity of S. aureus, regardless being MDR or susceptible, but slightly
      affect the membrane fluidity of E. coli.

PMID- 29567317
TI  - Improvement of the mechanical, tribological and antibacterial properties of glass
      ionomer cements by fluorinated graphene.
AB  - OBJECTIVE: The aim of this study was to improve the mechanical properties, wear
      resistance and antibacterial properties of conventional glass ionomer cements
      (GICs) by fluorinated graphene (FG), under the premise of not influencing their
      solubility and fluoride ion releasing property. MATERIALS AND METHODS: FG with
      bright white color was prepared using graphene oxide by a hydrothermal reaction.
      Experimental modified GICs was prepared by adding FG to the traditional GICs
      powder with four different weight ratios (0.5wt%, 1wt%, 2wt% and 4wt%) using
      mechanical blending. Compressive and flexural strength of each experimental and
      control group materials were investigated using a universal testing machine. The
      Vickers microhardness of all the specimens was measured by a Vicker microhardness
      tester. For tribological properties of the composites, specimens of each group
      were investigated by high-speed reciprocating friction tester. Fluoride ion
      releasing was measured by fluoride ion selective electrode methods. The
      antibacterial effect of GICs/FG composites on selected bacteria (Staphylococci
      aureus and Streptococcus mutans) was tested with pellicle sticking method.
      RESULTS: The prepared GICs/FG composites with white color were successfully
      fabricated. Increase of Vickers microhardness and compressive strength and
      decrease of friction coefficient of the GICs/FG composites were achieved compared
      to unreinforced materials. The colony count against S. aureus and S. mutans
      decreased with the increase of the content of FG. And the antibacterial rate of
      S. mutans can be up to 85.27% when the FG content was 4wt%. Additionally,
      fluoride ion releasing property and solubility did not show significant
      differences between unreinforced and FG reinforced GICs. SIGNIFICANCE: Adding FG
      to traditional GICs could not only improve mechanical and tribological properties
      of the composites, but also improve their antibacterial properties. In addition,
      the GICs/FG composites had no negative effect on the color, solubility and
      fluoride ion releasing properties, which will open up new roads for the
      application of dental materials.

PMID- 29567318
TI  - HMGB1 regulates T helper 2 and T helper17 cell differentiation both directly and
      indirectly in asthmatic mice.
AB  - The Th (T helper) 2 response is characteristic of allergic asthma, and Th17 cells
      are involved in more severe asthma. Recent studies demonstrated that HMGB1 (High
      mobility group box 1 protein) regulates airway inflammation and the Th2, Th17
      inflammatory response in asthma. HMGB1 can interact with Toll-like receptors
      (TLR) 2 and 4, and the receptor for advanced glycation end products (RAGE),
      activating the NF-kappaB (nuclear factor kappa B) signaling pathway and inducing
      the release of downstream inflammatory mediators. Both Th cells and dendritic
      cells express TLR2, TLR4, and RAGE receptors. Therefore, we speculate that HMGB1
      could regulate the differentiation of Th2, Th17 cells in asthma through direct
      and indirect mechanisms. An ovalbumin (OVA)-induced mouse asthmatic model was
      established. Anti-HMGB1 antibody or rHMGB1 was administered to OVA-sensitized
      mice 30 min prior to each challenge. For in vitro studies, magnetically separated
      CD4+ naive T cells were stimulated with or without rHMGB1 and/or anti-HMGB1
      antibody. BMDCs (bone marrow-derived dendritic cells)-stimulated with or without
      rHMGB1 and/or anti-HMGB1 antibody were cocultured with CD4+ naive T cells. Our
      study showed that administration of rHMGB1 aggravated airway inflammation and
      mucus production, and induced Th2, Th17 polarization in asthmatic mice, and that
      anti-HMGB1 antibody weakened characteristic features of asthma and blocked the
      Th2, Th17 inflammatory responses. HMGB1 could directly act on naive T cells to
      induce differentiation of Th2, Th17 cells in vitro through activating the TLR2,
      TLR4, RAGE-NF-kappaB signal pathway in CD4+ naive T cells. HMGB1 could also
      indirectly promote Th2, Th17 differentiation via activating the TLR2, TLR4, RAGE
      NF-kappaB signal pathway in DCs to mediate their maturation and antigen
      presenting ability in vitro.

PMID- 29567319
TI  - In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.
AB  - Effective control of Mycobacterium tuberculosis is a global necessity. In 2015,
      tuberculosis (TB) caused more deaths than HIV. Considering the increasing
      prevalence of multi-drug resistant forms of M. tuberculosis, the need for
      effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine
      is Bacillus Calmette-Guerin (BCG). Yet, BCG has many drawbacks limiting its
      efficacy and applicability. We applied advanced computational procedures to
      derive a universal TB vaccine and one targeting East Africa. Our approach selects
      an optimal set of highly conserved, experimentally validated epitopes, with high
      projected population coverage (PPC). Through rigorous data analysis, five
      different potential vaccine combinations were selected each with PPC above 80%
      for East Africa and above 90% for the World. Two potential vaccines only
      contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes.
      Our prime vaccine candidate was a putative seven-epitope ensemble comprising:
      SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL,
      QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC.

PMID- 29567320
TI  - Ultrasound-guided coracohumeral ligament release.
AB  - Long-term follow-up of patients with adhesive capsulitis (AC) reveals that
      approximately half of them suffer from a limited range of shoulder motion,
      particularly external and/or internal rotation. We report the surgical technique
      and short-term clinical outcomes of ultrasound-guided release of the thickened
      coracohumeral (CH) ligament in 8 patients (9 shoulders) with AC. Passive external
      rotation with the arm by the side significantly increased from an average of 18
      degrees  preoperatively to 47 degrees  immediately after CH ligament release. VAS
      and ASES scores were improved at 3months follow-up in all 9 shoulders, and
      maintained at 6months follow-up in 6 shoulders. No procedure-related adverse
      events developed over the 6-month follow-up period. Ultrasound-guided release for
      thickened CH ligament is a reliable and effective minimally invasive surgery for
      persistent limited external rotation due to AC of the shoulder.

PMID- 29567321
TI  - Effect of early fasting and total parenteral nutrition support on the healing of
      incision and nutritional status in patients after sacrectomy.
AB  - INTRODUCTION: Surgical site infection is one of the most common complications for
      patients after sacrectomy, which often accompanied by poor wound healing, sinus
      formation and serious metabolic disturbance. HYPOTHESIS: We tried to avoid the
      surgical site infection caused by feces during early period after surgery through
      early fasting and total parenteral nutrition (TPN) support, then compared the
      clinical results of these patients with other patients that received enteral
      nutrition (EN) early after sacrectomy. METHODS: Forty-eight patients after
      sacrectomy (the level of sacrectomy above S2) were randomly divided into two
      groups: TPN group and EN group. The patients of two groups received different
      nutrition support from the first day to the seventh day after surgery, then the
      factors such as nutritional and metabolic status after surgery, incidence of
      complications as well as the time of incision healing and hospitalization were
      observed. RESULTS: The p-value of total serum protein, albumin, serum alanine
      aminotransferase, total bilirubin at seventh day after sacrectomy between TPN
      group and EN group is <0.0005. The p-value of hemoglobin at seventh day after
      sacrectomy between TPN group and EN group is 0.001. The p-value of total serum
      protein at fourteenth day after sacrectomy between TPN group and EN group is
      0.003. The p-value of albumin and total bilirubin at fourteenth day after
      sacrectomy between TPN group and EN group is 0.001. The p-value of hemoglobin,
      serum alanine aminotransferase at fourteenth day after sacrectomy between TPN
      group and EN group is <0.0005. The incidence of gastrointestinal complication and
      delay of apparition of feces in EN group were lower than that in TPN group
      (p=0.041, p<0.0005). The incidence of surgical site infection, the time of
      incision healing and hospitalization in TPN group were lower than that in EN
      group (p=0.048, p=0.008, p<0.0005). CONCLUSIONS: The method of fasting and
      supported by TPN during the early period after sacrectomy contribute to the
      incision healing, meanwhile, it shortens the hospitalization time and abates the
      incidence of complications in patients after sacrectomy. TYPE OF STUDY: It is a
      comparative randomized study. LEVEL OF PROOF: High-powered prospective randomized
      trial.

PMID- 29567322
TI  - Collection and reconstruction after harvesting donor tissues from the
      musculoskeletal system: Technique specific to the lower limbs.
AB  - The lack of available musculoskeletal grafts in France forces us to import a very
      large quantity of these tissues to use in complex reconstruction procedures. The
      goal of this article is to describe methods for collecting donor tissues from the
      musculoskeletal system and for reconstructing the harvested areas. We also
      provide a summary of the collection procedures performed, harvested grafts and
      available tissues. While tissue collection requires a significant time
      investment, the emergence of dedicated teams may be a solution for increasing the
      number and quality of human musculoskeletal allograft tissues.

PMID- 29567323
TI  - Circular RNA (circRNA) was an important bridge in the switch from the RNA world
      to the DNA world.
AB  - The concept that life on Earth began as an RNA world has been built upon
      extensive experimentation demonstrating that many of the building blocks required
      for living cells could be synthesized in the laboratory under conditions
      approximating our primordial world. Many of the building blocks for life have
      also been found in meteorites indicating that meteors may have been a source for
      these molecules, or more likely, that they represent the chemical library present
      in most/all bodies in the universe after the big bang. Perhaps the most important
      support for the concept comes from the fact that some RNA species possess
      catalytic activity, ribozymes, and that RNA could be reverse transcribe to DNA.
      The thrust of numerous papers on this topic has been to explore how the available
      molecules on Earth, at its birth, gave rise to life as we know it today. This
      paper focuses more on a reverse view of the topic. The "how" molecular building
      blocks were synthesized is not addressed nor how the "first" RNA molecules were
      synthesized. We can clearly speculate on the variable environmental conditions
      and chemistry available on Earth billions of years ago. However, we can never
      truly replicate the changing conditions or know the chemical composition of Earth
      at the beginning of time. We can, however, confirm that over millions, perhaps
      billions of years the basic building blocks for life accumulated sufficiently to
      initiate evolution to an RNA world followed by our RNA/DNA world. Here we are
      attempting to take the information from our current knowledge of biology and by
      inference and extrapolation work backward to hypothesize biological events in the
      march forward from RNA to DNA. It is proposed that the primordial replicating RNA
      cell, the ribocyte, evolved from liposomes encompassing required reactants and
      products for "life" and that ribonucleopeptide complexes formed membrane pores to
      support bidirectional ion and molecular transport to maintain biological
      functions and osmolarity. Circular RNA, circRNA, is proposed as a critical stable
      RNA molecule that served as the genetic precursor for the switch to DNA and the
      replication of circRNA by a rolling circle mechanism gave rise to the RNA
      complexity required for the genetic functions of the cell. The replicating
      ribocyte would have required protein synthesis as well as RNA replication and a
      model for non-coded and primordial coded protein synthesis is proposed. Finally,
      the switch from the RNA to the DNA world would have involved the synthesis of an
      RNA:DNA hybrid prior to the formation of dsDNA. If the hybrid was a circular
      molecule that ultimately yielded a circular dsDNA molecule, it could predict that
      the primordial DNA cell would evolve into a bacterial cell with a single circular
      chromosome. One would hope that continued speculation of the origin of life will
      spur new directions of research that may never fully answer the questions of the
      past but add to our ability to regulate potentially harmful biological events in
      the present and in the future.

PMID- 29567324
TI  - Multiplicity of phenotypes and RNA evolution.
AB  - Motivation Motoo Kimura's neutral theory stipulates that evolution is
      predominantly driven by neutral mutations. RNA, realizing both genotype (its
      linear sequence of nucleotides) as well as phenotype (its folded secondary
      structure) represents a particularly well suited test bed for studying
      neutrality. This leads to neutral networks of RNA secondary structures, i.e. sets
      of sequences all of which folding into a fixed phenotype and whose organization
      plays a crucial role for neutral evolution. In this paper we bring a new
      perspective to the neutral theory by studying the consequences of the mostly
      ignored fact that the genotype-to-phenotype map for RNA is often one-to-many. In
      fact 29.5% of random RNA sequences realize more than one phenotype (minimum free
      energy structure). We call two genotypes to be quasineutral if their sets of
      associated phenotypes have non-empty intersection. Results We show that even
      though the energy profile of quasineutral mutations is almost identical to the
      neutral ones, a walk in the genotype space whose consecutive steps are
      quasineutral, can percolate phenotype space and so such walks bridge between
      neutral and random walks. This provides further evidence that evolution is
      continuous. We also study how these drift walks transition between neutral
      networks.

PMID- 29567325
TI  - Mate sampling influences the intensity of sexual selection and the evolution of
      costly sexual ornaments.
AB  - Mate choice includes three steps: (1) a choosing individual encounters potential
      mates, (2) assesses and processes information about them, and (3) makes a mate
      decision. During mate searching females can access only a sample of males in the
      mating pool and need to choose their mates based on limited information. Thus,
      mate sampling may influence sexual selection promoted by mate choice because it
      constrains female choice. Using individual-based simulations, we found that both
      female choosiness and mate sampling influenced the variance in mating success
      among males and thus the intensity of sexual selection. So that sexual selection
      is most intense when females are strongly choosy and can sample many males.
      Moreover, in evolutionary simulations, the rate of evolutionary change and the
      final size of male ornament increase with increasing mate sampling. However,
      under stronger natural selection, evolutionary change is slower and leads to
      smaller ornaments. Empirical data on the potential for sexual selection (Is) for
      several animal species show a positive correlation between the intensity of
      sexual selection and an index of mate sampling based on behavioral and ecological
      traits. Based on the results of our simulations, we predict that males of highly
      mobile species with long-range sexual signal transmission, which allow females to
      assess many males, will show greater variance in mating success and will be more
      ornamented than their relatives not exhibiting these features.

PMID- 29567326
TI  - Lysine Deacetylases and Regulated Glycolysis in Macrophages.
AB  - Regulated cellular metabolism has emerged as a fundamental process controlling
      macrophage functions, but there is still much to uncover about the precise
      signaling mechanisms involved. Lysine acetylation regulates the activity,
      stability, and/or localization of metabolic enzymes, as well as inflammatory
      responses, in macrophages. Two protein families, the classical zinc-dependent
      histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs),
      mediate lysine deacetylation. We describe here mechanisms by which classical
      HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as
      evidence that links these protein deacetylases to the regulation of glycolysis
      related genes. In these contexts, we discuss HDACs and SIRTs as key control
      points for regulating immunometabolism and inflammatory outputs from macrophages.

PMID- 29567327
TI  - Origin and Immunological Functions of Spleen Stromal Cells.
AB  - The mammalian spleen is a peripheral lymphoid organ that plays a central role in
      host defense. Consequently, the lack of spleen is often associated with
      immunodeficiency and increased risk of overwhelming infections. Growing evidence
      suggests that non-hematopoietic stromal cells are central players in spleen
      development, organization, and immune functions. In addition to its immunological
      role, the spleen also provides a site for extramedullary hematopoiesis (EMH) in
      response to injuries. A deeper understanding of the biology of stromal cells is
      therefore essential to fully comprehend how these cells modulate the immune
      system during normal and pathological conditions. Here, we review the
      specificities of the different mouse spleen stromal cell subsets and complement
      the murine studies with human data when available.

PMID- 29567328
TI  - Literature-based safety assessment of an agriculture- and animal-associated
      microorganism: Weissella confusa.
AB  - Although Weissella confusa was established as a species over 25 years ago, it has
      been understudied until very recently. Several independent observations have
      driven the recent interest in this important microorganism. First, this
      Leuconostoc-like species of Lactic Acid Bacteria is associated with agricultural
      environments, many spontaneous food fermentations-especially carbohydrate-rich
      vegetable fermentations-and silage. Second, Weissella confusa are members of the
      autochthonous microbiota of healthy humans and livestock. Third, Weissella
      confusa-in a strain-specific fashion-are postulated to be good candidates for the
      development of novel direct-fed microbial products. Fourth, Weissella confusa-in
      a strain-specific fashion-have been described as opportunistic pathogens
      especially in immunocompromised individuals. Last, a distantly related species
      (Weissella ceti) is the etiologic agent of weissellosis, a disease that affects
      farmed fish that are important for commercial aquaculture. The purpose of this
      literature-based safety assessment is to consolidate findings from primary
      research related to Weissella confusa and its natural associations with and
      effects on animals, humans, and their agricultural environments. Based on these
      assessments, it is reasonable to conclude that many Weissella confusa are safe
      for use in direct-fed microbial products for poultry.

PMID- 29567329
TI  - Acute and repeated dose 28-day oral toxicity of poly(3-hydroxybutyrate-co-4
      hydroxybutyrate) nanoparticles in Sprague-Dawley rats.
AB  - This study aimed to investigate the oral acute and subacute toxicity of Poly [3
      hydroxybutyrate-co-4-hydroxybutyrate], P(3HB-co-4HB) in the form of nanoparticles
      in Sprague-Dawley rats. Acute oral administration of P(3HB-co-4HB) nanoparticles
      was performed as a single dose up to 2000 mg/kg in six female rats for 14 days.
      Subacute toxicity study via oral administration for 28 days at doses of 0
      (control), 500, 1000 and 2000 mg/kg in rats (10 rats in each group, female:male =
      1:1) was conducted. The estimated lethal dose (LD50) of P(3HB-co-4HB)
      nanoparticles was >2000 mg/kg. No mortality, unusual changes in behaviour,
      adverse clinical signs, abnormal changes in body weights or food consumption were
      observed on all animals treated with P(3HB-co-4HB) nanoparticles during 14 days
      of the acute toxicity study. In the subacute test, there was no mortality and
      toxicologically significant changes in clinical signs, body weights, food
      consumption, hematology, clinical biochemistry, urinalysis, macroscopic findings,
      organ weights as well as histopathological examination were observed.

PMID- 29567330
TI  - Dietary supplement intake during pregnancy; better safe than sorry?
AB  - Consumption of dietary supplements and specifically niche products such as
      supplements targeting pregnant women is increasing. The advantages of dietary
      supplementation during pregnancy with folic acid have been established, but
      health effects of many other supplements have not been confirmed. EU and US
      legislation on dietary supplements requires the product to be safe for the direct
      consumer, the mother. Long-term health effects for the fetus due to fetal
      programming (in utero adaptation of the fetal epigenome due to environmental
      stimuli such as supplementation) are not taken into account. Such epigenetic
      alterations can, however, influence the response to health challenges in
      adulthood. We therefore call for both conducting research in birth cohorts and
      animal studies to identify potential health effects in progeny of supplement
      consuming mothers as well as the establishment of a nutrivigilance scheme to
      identify favorable and adverse effects post-marketing. The acquired knowledge can
      be used to create more effective legislation on dietary supplement intake during
      pregnancy for safety of the child. Increasing knowledge on the effects of
      consuming supplements will create a safer environment for future mothers and
      their offspring to optimize their health before, during and after pregnancy.

PMID- 29567331
TI  - An evaluation of electronic cigarette formulations and aerosols for harmful and
      potentially harmful constituents (HPHCs) typically derived from combustion.
AB  - U.S. FDA draft guidance recommends reporting quantities of designated harmful and
      potentially harmful constituents (HPHCs) in e-cigarette e-liquids and aerosols.
      The HPHC list comprises potential matrix-related compounds, flavors, nicotine,
      tobacco-related impurities, leachables, thermal degradation products, and
      combustion-related compounds. E-cigarettes contain trace levels of many of these
      constituents due to tobacco-derived nicotine and thermal degradation. However,
      combustion-related HPHCs are not likely to be found due to the relatively low
      operating temperatures of most e-cigarettes. The purpose of this work was to use
      highly sensitive, selective, and validated analytical methods to determine if
      these combustion-related HPHCs (three aromatic amines, five volatile organic
      compounds, and the polycyclic aromatic hydrocarbon benzo[a]pyrene) are detectable
      in commercial refill e-liquids, reference e-cigarette e-liquids, and aerosols
      generated from rechargeable e-cigarettes with disposable cartridges (often
      referred to as "cig-a-likes"). In addition, the transfer efficiency of these
      constituents from e-liquid to aerosol was evaluated when these HPHCs were added
      to the e-liquids prior to aerosol formation. This work demonstrates that
      combustion-related HPHCs are not present at measurable levels in the commercial
      and reference e-liquids or e-cigarette aerosols tested. Additionally, when
      combustion-related HPHCs are added to the e-liquids, they transfer to the aerosol
      with transfer efficiencies ranging from 49% to 99%.

PMID- 29567332
TI  - miR-486-5p functions as an oncogene by targeting PTEN in non-small cell lung
      cancer.
AB  - PURPOSE: Lung cancer, the leading cause of cancer-related death worldwide, shows
      a poor 5-year overall survival rate. In our previous study, we demonstrated that
      miR-486-5p can be a potential blood-based biomarker for early diagnosis and
      recurrence prediction of non-small cell lung cancer (NSCLC). The aim of the
      present study was to investigate the possible roles and related target genes of
      miR-486-5p in NSCLC progression. METHODS: pcDNA3.1(+)/Pri-miR486 recombinant
      plasmid and miR-486-5p inhibitor were transfected into NSCLC cells and theirs
      effects were evaluated by qRT-PCR. Then, MTT assay and Colony formation assay
      were performed to determine the potential roles of miR-486-5p played on NSCLC
      cellular proliferation and cloning in vitro. We also initially investigated the
      target genes of miR-486-5p by using bioinformatic methods, qRT-PCR and western
      blot. RESULTS: pcDNA3.1(+)/Pri-miR486 recombinant plasmid significantly
      upregulated the expression of miR-486-5p, while miR-486-5p inhibitor
      significantly downregulated its expression. Upregulation of miR-486-5p promoted
      the cellular proliferation and cloning, while miR-486-5p silencing restrained the
      cellular proliferation and cloning. Furthermore, four potential target genes
      (PIK3R1, PTEN, MAP3K7 and FOXO1) of miR-486-5p were screened out. Finally, we
      found that upregulation of miR-486-5p in NSCLC cells significantly reduced PTEN
      and increased AKT expression levels, whereas miR-486-5p silencing increased PTEN
      and reduced AKT expression. Therefore, we believe that miR-486-5p can regulate
      PTEN-PI3 K/AKT signaling. CONCLUSIONS: miR-486-5p acts as an oncogene in the
      progression of NSCLC by influencing PTEN-PI3 K/AKT signaling. miR-486-5p may
      provide potential therapeutic targets for NSCLC.

PMID- 29567333
TI  - Chinese herb medicine matrine induce apoptosis in human esophageal squamous
      cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting
      mitochondrial function.
AB  - Matrine, as a natural alkaloid isolated from the traditional herb medicine
      sophora flavescens, has been proved to possess excellent biological activities,
      including anticancer effects. Now, this research aims to assess the anticancer
      activities and the mechanism of matrine against esophageal cancer cells, we
      investigated the proliferative inhibition, apoptosis induction, as well as the
      underlying mechanism of matrine on esophageal cancer KYSE-150 cells. It was found
      that matrine could suppress KYSE-150 cell proliferation and significantly mediate
      cell apoptosis in a dose-dependent relation by increasing intracellular reactive
      oxygen species level and triggering mitochondrial membrane potential disruption.
      More precise mechanism studies demonstrated that matrine could up-regulate the
      expression of Bax proteins and down-regulate the expression of Bcl-2 proteins, as
      well as the activation about caspase-3, 8 and 9 in KYSE-150 cells. The
      morphological analysis of KYSE-150 cells exhibited that matrine could destroy the
      F-actin and nuclei structures and induce morphological damage with increased
      surface height distribution and roughness of cell membrane. These results not
      only demonstrated the potential anticancer activity mechanism of matrine at
      nanoscale, but also provide preliminary guidance for the treatment of esophageal
      cancer using matrine.

PMID- 29567334
TI  - Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head
      and neck squamous cell carcinoma in Japan.
AB  - OBJECTIVE: Recent data indicated that concurrent chemoradiotherapy (CCRT) using
      high dose cisplatin (CDDP) is the most useful treatment for advanced head and
      neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most
      recommended in Western countries. However, in terms of a balance of efficacy and
      adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different
      among the different ethnic groups. In this multicenter phase I/II study, we aimed
      to identify the optimal dose of CDDP in CCRT for patients with advanced head and
      neck SCC in the Japanese. METHODS: Patients were eligible for inclusion if they
      had head and neck SCC that was treated with radical CCRT comprising whole-neck
      irradiation of the primary lesion and level II-IV lymph nodes on both sides. For
      the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and
      100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity
      (DLT) were examined by phase I trial, by which CDDP dose for phase II was
      determined. The primary endpoint for the phase II was CCRT completion rate, and
      the secondary endpoint was full-dose-CCRT completion rate, the percentage of
      patients receiving a total CDDP dose of >=200mg/m2, response rate, and incidences
      of adverse events. RESULTS: A CDDP dose of 100mg/m2 was the MTD for phase I, and
      the recommended dose for phase II was 80 mg/m2. Forty-seven patients were
      evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and
      the percentage of patients receiving a total CDDP dose of >=200mg/m2, were 93.6%,
      78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal
      dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse
      event. CONCLUSION: The present phase I study indicated that a CDDP dose of
      80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that
      CCRT completion rate, response rate, and rates of adverse events were not
      inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a
      dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was
      registered with the University Hospital Medical Information Network Clinical
      Trials Registry (UMIN-CTR; identification No. UMIN000010369).

PMID- 29567335
TI  - Effect of family nursing therapeutic conversations on health-related quality of
      life, self-care and depression among outpatients with heart failure: A randomized
      multi-centre trial.
AB  - OBJECTIVE: To evaluate the short-term (3 months) effects of family nursing
      therapeutic conversations (FNTC) on health-related quality of life, self-care and
      depression in outpatients with Heart failure (HF). METHODS: A randomised multi
      centre trial was conducted in three Danish HF clinics. The control group (n =
      167) received usual care, and the intervention group (n = 180) received FNTCs as
      supplement to usual care. Primary outcome was clinically significant changes (6
      points) in Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score between
      groups. Secondary outcomes were changes in self-care behaviour and depression
      scores. Data were assessed before first consultation and repeated after three
      months. RESULTS: No statistically significant difference was found in the change
      of KCCQ, self-care and depression scores between the groups. KCCQ scores of
      patients in the FNTC group changed clinically significant in seven domains,
      compared to one domain in the control group, with the highest improvement in self
      efficacy, social limitation and symptom burden. CONCLUSION: FNTC was not superior
      to standard care of patients with HF regarding health-related quality of life,
      self-care and depression. IMPLICATION FOR PRACTICE: Addressing the impact of the
      disease on the family, might improve self-efficacy, social limitation and symptom
      burden in patients with heart failure.

PMID- 29567337
TI  - Biomarkers of glomerular dysfunction in pre-eclampsia - A systematic review.
AB  - BACKGROUND: Early detection of pre-eclampsia remains one of the major focuses of
      antenatal obstetric care. There is often a delay in the diagnosis, mainly due to
      the non-specific nature of the condition. Podocytes which play a pivotal role in
      glomerular function become injured in pre-eclampsia leading to subsequent
      proteinuria. Our aim was to review available studies to determine the clinical
      utility of biomarkers of podocyte injury in pre-eclampsia. METHODS: We used
      QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a
      systematic review of the literature to determine the clinical utility of podocyte
      injury biomarkers in predicting pre-eclampsia. RESULTS: This study identified
      five potential renal biomarkers including podocytes, nephrin, synaptopodin,
      podocin and podocalyxin. The pooled sensitivity of all biomarkers was 0.78 (95%
      CI 0.74-0.82) with a specificity of 0.82 (95% CI 0.79-0.85). The area under the
      Summary of Receiver Operating Characteristics Curve (SROC) was 0.926 (SE 0.30).
      Urinary nephrin achieved the highest diagnostic values with a sensitivity of 0.81
      (95% CI 0.72-0.88) and specificity of 0.84 (95% CI 0.79-0.84). CONCLUSION:
      Biomarkers of glomerular injury show promise as diagnostic aids in pre-eclampsia.
      A large-scale prospective cohort study is warranted before these biomarkers can
      be recommended for routine clinical care.

PMID- 29567338
TI  - Novel piperidine-derived amide sEH inhibitors as mediators of lipid metabolism
      with improved stability.
AB  - We have previously identified and reported several potent piperidine-derived
      amide inhibitors of the human soluble epoxide hydrolase (sEH) enzyme. The
      inhibition of this enzyme leads to elevated levels of epoxyeicosatrienoic acids
      (EETs), which are known to possess anti-inflammatory, vasodilatory, and anti
      fibrotic effects. Herein, we report the synthesis of 9 analogs of the lead sEH
      inhibitor and the follow-up structure-activity relationship and liver microsome
      stability studies. Our findings show that isosteric modifications that lead to
      significant alterations in the steric and electronic properties at a specific
      position in the molecule can reduce the efficacy by up to 75-fold. On the other
      hand, substituting hydrogen with deuterium produces a notable increase (~30%) in
      the molecules' half-lives in both rat and human microsomes, while maintaining sEH
      inhibition potency. These data highlight the utility of isosteric replacement for
      improving bioavailability, and the newly-synthesized inhibitor structures may
      thus, serve as a starting point for preclinical development. Our docking study
      reveals that in the catalytic pocket of sEH, these analogs are in proximity of
      the key amino acids involved in hydrolysis of EETs.

PMID- 29567336
TI  - Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human
      Genetics.
AB  - Over 30 hereditary diseases are caused by the expansion of microsatellite
      repeats. The length of the expandable repeat is the main hereditary determinant
      of these disorders. They are also affected by numerous genomic variants that are
      either nearby (cis) or physically separated from (trans) the repetitive locus,
      which we review here. These genetic variants have largely been elucidated in
      model systems using gene knockouts, while a few have been directly observed as
      single-nucleotide polymorphisms (SNPs) in patients. There is a notable disconnect
      between these two bodies of knowledge: knockouts poorly approximate the SNP-level
      variation in human populations that gives rise to medically relevant cis- and
      trans-modifiers, while the rarity of these diseases limits the statistical power
      of SNP-based analysis in humans. We propose that high-throughput SNP-based
      screening in model systems could become a useful approach to quickly identify and
      characterize modifiers of clinical relevance for patients.

PMID- 29567339
TI  - Management of failure after surgery for gastro-esophageal reflux disease.
AB  - Surgical treatment of gastro-esophageal reflux disease (ST-GERD) is well-codified
      and offers an alternative to long-term medical treatment with a better efficacy
      for short and long-term outcomes. However, failure of ST-GERD is observed in 2
      20% of patients; management is challenging and not standardized. The aim of this
      study is to analyze the causes of failure and to provide a treatment algorithm.
      The clinical aspects of ST-GERD failure are variable including persistent reflux,
      dysphagia or permanent discomfort leading to an important degradation of the
      quality of life. A morphological and functional pre-therapeutic evaluation is
      necessary to: (i) determine whether the symptoms are due to recurrence of reflux
      or to an error in initial indication and (ii) to understand the cause of the
      failure. The most frequent causes of failure of ST-GERD include errors in the
      initial indication, which often only need medical treatment, and surgical
      technical errors, for which surgical redo surgery can be difficult.
      Multidisciplinary management is necessary in order to offer the best-adapted
      treatment.

PMID- 29567341
TI  - A pilot study assessing retinal pathology in psychosis using optical coherence
      tomography: Choroidal and macular thickness.
AB  - Mounting evidence supports a genetic-vascular-inflammatory etiology of
      schizophrenia. The retina provides an indirect assessment of inflammation and
      degeneration in the brain. In particular, the use of spectral domain optical
      coherence tomography (SD-OCT) has emerged as a powerful tool for examining single
      retinal nerve cell layers and the choroid, the vascular layer supplying the outer
      retina. In this study, choroidal and macular thicknesses were measured in six
      patients with psychosis with either schizophrenia or bipolar disorder, and in 18
      age- and sex-matched healthy controls. Mean choroidal thickness was reduced in
      psychosis, though not significantly so. There was a statistically significant
      decrease in macular thickness in psychosis patients predominantly affecting the
      inner layers of the macula. Significant macular thinning may signal vascular,
      inflammatory, or degenerative processes that may also be occurring in the brain.
      This is one of the first studies to examine choroidal thickness in psychosis.
      Further studies are needed to determine whether the retinal changes in psychosis
      are correlated with microvascular dysfunction, neuroinflammation, and
      neurodegeneration.

PMID- 29567342
TI  - Mechanical stress in plates for bridging reconstruction mandibular defects and
      purposes of double plate reinforcement.
AB  - PURPOSE: To evaluate the biomechanical performance of a commercially available
      bridging plate (2.4) as well as screws and bone simulating the reconstruction of
      hemimandibular defects and to indicate alternatives of reinforcement to prevent
      plate fractures either by strength or fatigue. MATERIAL AND METHODS: Two common
      hemimandibular defects are investigated using computed finite element analysis
      (FEA) approach. Simplified and refined computational models are developed for the
      geometry of the screw. Conditions of non-locking and locking plate-screw
      interfaces are considered. Static loads of 120 N are applied. Von Mises stresses
      and fatigue are calculated. As reinforcement, a second complete or partial plate
      is placed onto the original plate. RESULTS: Results demonstrate that
      reconstruction plates are often subjected to excessive stress that may lead to
      fracture either by strength or by fatigue. An attached complete or partial second
      plate is able to reduce stress in the plate, in screws and bone so that stress
      remains below the allowable limit of the materials. CONCLUSION: A simplified
      technique of attaching a whole or sectioned second plate onto the original plate
      can reduce the stress calculated and may reduce the frequency of plate fractures
      for the patient's comfort, security and financial savings.

PMID- 29567340
TI  - Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic
      Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A
      CIBMTR Analysis.
AB  - For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic
      cell transplantation (alloHCT) offers a potential cure. Life-threatening
      complications can arise from alloHCT that require the application of
      sophisticated health care delivery. The impact of country-level economic
      conditions on post-transplantation outcomes is not known. Our objective was to
      assess whether these variables were associated with outcomes for patients
      transplanted for ALL. Using data from the Center for Blood and Marrow Transplant
      Research, we included 11,261 patients who received a first alloHCT for ALL from
      303 centers across 38 countries between the years of 2005 and 2013. Cox
      regression models were constructed using the following macroeconomic indicators
      as main effects: Gross national income per capita, health expenditure per capita,
      and Human Development Index (HDI). The outcome was overall survival at 100 days
      following transplantation. In each model, transplants performed within lower
      resourced environments were associated with inferior overall survival. In the
      model with the HDI as the main effect, transplants performed in the lowest HDI
      quartile (n = 697) were associated with increased hazard for mortality (hazard
      ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with
      transplants performed in the countries with the highest HDI quartile. This
      translated into an 11% survival difference at 100 days (77% for lowest HDI
      quartile versus 88% for all other quartiles). Country-level macroeconomic indices
      were associated with lower survival at 100 days after alloHCT for ALL. The
      reasons for this disparity require further investigation.

PMID- 29567343
TI  - Value of PET/CT 3D visualization of head and neck squamous cell carcinoma
      extended to mandible.
AB  - PURPOSE: To study an original 3D visualization of head and neck squamous cell
      carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG
      PET/CT imaging along with a new innovative FDG and NaF image analysis using
      dedicated software. The main interest of the 3D evaluation is to have a better
      visualization of bone extension in such cancers and that could also avoid
      unsatisfying surgical treatment later on. PATIENTS AND METHODS: A prospective
      study was carried out from November 2016 to September 2017. Twenty patients with
      head and neck squamous cell carcinoma extending to the mandible (stage 4 in the
      UICC classification) underwent [18F]-NaF and [18F]-FDG PET/CT. We compared the
      delineation of 3D quantification obtained with [18F]-NaF and [18F]-FDG PET/CT. In
      order to carry out this comparison, a method of visualisation and quantification
      of PET images was developed. This new approach was based on a process of
      quantification of radioactive activity within the mandibular bone that
      objectively defined the significant limits of this activity on PET images and on
      a 3D visualization. Furthermore, the spatial limits obtained by analysis of the
      PET/CT 3D images were compared to those obtained by histopathological examination
      of mandibular resection which confirmed intraosseous extension to the mandible.
      RESULTS: The [18F]-NaF PET/CT imaging confirmed the mandibular extension in 85%
      of cases and was not shown in [18F]-FDG PET/CT imaging. The [18F]-NaF PET/CT was
      significantly more accurate than [18F]-FDG PET/CT in 3D assessment of
      intraosseous extension of head and neck squamous cell carcinoma. This new 3D
      information shows the importance in the imaging approach of cancers. All cases of
      mandibular extension suspected on [18F]-NaF PET/CT imaging were confirmed based
      on histopathological results as a reference. CONCLUSIONS: The [18F]-NaF PET/CT 3D
      visualization should be included in the pre-treatment workups of head and neck
      cancers. With the use of a dedicated software which enables objective delineation
      of radioactive activity within the bone, it gives a very encouraging results. The
      [18F]-FDG PET/CT appears insufficient to confirm mandibular extension. This new
      3D simulation management is expected to avoid under treatment of patients with
      intraosseous mandibular extension of head and neck cancers. However, there is
      also a need for a further study that will compare the interest of PET/CT and
      PET/MRI in this indication.

PMID- 29567344
TI  - Enantiomeric neolignans from Picrasma quassioides exhibit distinctive
      cytotoxicity on hepatic carcinoma cells through ROS generation and apoptosis
      induction.
AB  - Three pairs of enantiomeric neolignans 1a/1b-3a/3b were isolated from the stems
      of Picrasma quassioides, and separated successfully by chiral-phase HPLC. Their
      structures were established by comprehensive spectroscopic analyses as well as
      ECD spectroscopy. The in vitro cytotoxicity of the isolates was evaluated against
      human hepatocellular carcinoma HepG2 and Hep3B cells. Among them, 1 and its
      enantiomers 1a/1b, 3 and 3a/3b displayed similar cytotoxicity in pair-wise
      comparison against HepG2 and Hep3B cells, and the similar effects of 2 and 2a/2b
      were found in Hep3B cells. Interestingly, 2a and 2b had different cytotoxic
      activities on HepG2 cells with IC50 values of 35.6 MUM and 104.4 MUM,
      respectively. In addition, 2 exerted middle cytotoxicity against HepG2 cells with
      an IC50 value of 78.6 MUM. The different cytotoxicity between enantiomers 2a and
      2b attracted our interest. To investigate the underlying mechanisms responsible
      for the distinct cytotoxicity, we further assessed the effects of 2a and 2b on
      cell cycle distribution, cell apoptosis and reactive oxygen species (ROS)
      generation. The results indicated that 2a had more significant effect than 2b on
      apoptosis induction and ROS generation, but both had no obvious effect on cell
      cycle of HepG2 cells. It is concluded that the different configurations of 2a/2b
      determined the enantioselective cytotoxicity on HepG2 cells through apoptosis
      induction and ROS generation.

PMID- 29567345
TI  - Evaluation of analogues of furan-amidines as inhibitors of NQO2.
AB  - Inhibitors of the enzyme NQO2 (NRH: quinone oxidoreductase 2) are of potential
      use in cancer chemotherapy and malaria. We have previously reported that non
      symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues
      are evaluated. The furan ring has been changed to other heterocycles (imidazole,
      N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced
      with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity,
      improve solubility and decrease basicity of the lead furan amidine. All compounds
      were fully characterised spectroscopically and the structure of the unexpected
      product N-hydroxy-4-(5-methyl-4-phenylfuran-2-yl)benzamidine was established by X
      ray crystallography. The analogues were evaluated for inhibition of NQO2, which
      showed lower activity than the lead furan amidine. The observed structure
      activity relationship for the furan-amidine series with NQO2 was rationalized by
      preliminary molecular docking and binding mode analysis. In addition, the oxazole
      amidine analogue inhibited the growth of Plasmodium falciparum with an IC50 value
      of 0.3 MUM.

PMID- 29567346
TI  - Mycobacterium canettii pulmonary tuberculosis in an immunocompetent patient.

PMID- 29567347
TI  - Extrapolation of the Hepatic Clearance of Drugs in the Absence of Albumin In
      Vitro to That in the Presence of Albumin In Vivo: Comparative Assessement of 2
      Extrapolation Models Based on the Albumin-Mediated Hepatic Uptake Theory and
      Limitations and Mechanistic Insights.
AB  - The extrapolation of hepatic clearance (CL) from data determined in an in vitro
      assay in the absence of albumin (ALB) to that in the presence of ALB in liver in
      vivo was often inaccurate using traditional in vitro-to-in vivo extrapolation
      (IVIVE) methods for drugs binding to the ALB. It is recognized that considering
      an ALB-facilitated hepatic uptake phenomenon in the IVIVE can improve the
      extrapolation. Therefore, the present study provides a comparison of 2 existing
      models that account for the ALB-facilitated hepatic uptake phenomenon in the
      IVIVE of CL. These models assume an interaction of the ALB-bound drug complex
      with the hepatocyte membrane that enhanced the dissociation of the drug from ALB
      to result in increased unbound intracellular drug levels available for metabolism
      or transporter-mediated elimination. One model refers to the old facilitated
      dissociation model (FDM), which is based on a binding isotherm and necessitates
      knowing the specific input parameters of the interaction (i.e., relative capacity
      of the interaction, dissociation constant, number of binding sites, and ALB
      concentration). The other model is based on the same theory but is recent and
      more speculative although it presumes that each interaction between the ALB-drug
      complex and the hepatocyte surface would at all times enhance and deliver the
      dissociated bound drug moiety into the hepatocytes and therefore, has the
      advantage to use less binding information. Consequently, this second model simply
      consists of adjusting the unbound fraction determined in plasma in vitro of each
      drug (fup-adjusted) with the real differential of ALB concentration between the
      plasma and liver in vivo to estimate the corresponding differential of ALB-drug
      complex also assumed available to deliver the unbound drug moiety for hepatic
      uptake in vivo versus in vitro. Application of these 2 models (FDM and fup
      adjusted) significantly improved the IVIVEs of CL of drugs, and hence, the next
      step was to compare these 2 models with the same data set. Recently published
      data on the hepatic uptake of 2 organic anions, namely 1-anilino-8-naphthalene
      sulfonate and pitavastatin, provide all binding information. As expected, the
      results indicate that these 2 models are conceptually and mathematically
      equivalent as well as they successfully predicted the experimentally determined
      ratios of the unbound intrinsic CL (CLint) in the presence of ALB in vivo to that
      in the absence of ALB in vitro. However, the 2 models were equivalent
      particularly for pitavastatin because its ALB-drug complex showed a relevant
      capacity of interaction and dissociation with the hepatocyte membrane.
      Conversely, for 1-anilino-8-naphthalene sulfonate, the model of fup-adjusted
      overestimated the ratio of unbound CLint by contrast to the FDM model because its
      ALB-drug complex demonstrated a significantly lower capacity of interaction with
      the membrane. The rational is simply because the model of fup-adjusted presumably
      assumed an important facilitated-uptake phenomenon for each drug, whereas the FDM
      model was derived from binding data specific to each drug. Overall, these 2
      models are complementary, and all contribute toward achieving the same objective
      of quantifying the ALB-facilitated uptake phenomenon; however, the FDM model is
      more specific, but its application necessitates collecting more binding data
      compared with the model of fup-adjusted that can be used prospectively to predict
      the maximal effect of the facilitated-hepatic uptake in IVIVE.

PMID- 29567348
TI  - Transport and sorting in the Golgi complex: multiple mechanisms sort diverse
      cargo.
AB  - At the center of the secretory pathway, the Golgi complex ensures correct
      processing and sorting of cargos toward their final destination. Cargos are
      diverse in topology, function and destination. A remarkable feature of the Golgi
      complex is its ability to sort and process these diverse cargos destined for
      secretion, the cell surface, the lysosome, or retained within the secretory
      pathway. Just as these cargos are diverse so also are their sorting requirements
      and thus, their trafficking route. There is no one-size-fits-all sorting scheme
      in the Golgi. We propose a coexistence of models to reconcile these diverse
      needs. We review examples of differential sorting mediated by proteins and
      lipids. Additionally, we highlight recent technological developments that have
      potential to uncover new modes of transport.

PMID- 29567349
TI  - Whole exome sequencing discloses a pathogenic MTM1 gene mutation and ends the
      diagnostic odyssey in an older woman with a progressive and seemingly sporadic
      myopathy: Case report and literature review of MTM1 manifesting female carriers.
AB  - We report the case of a 58-year-old woman with a progressive and seemingly
      sporadic myopathy who, later through whole exome sequencing, was diagnosed as a
      manifesting carrier of a myotubularin 1 gene mutation (c.342_342 + 4delAGTAA). As
      the case was a diagnostic challenge for 7 years, we thought it would be helpful
      to report the patient and review the other 25 cases thus far described. The
      manifesting carrier state is a rare cause for myopathic weakness in a female but
      should be strongly considered in kindreds with known affected males with
      myotubularin 1 gene mutations, and families with history of gestational
      polyhydramnios or male infantile death. Although the clinical phenotype is quite
      variable, the findings of ptosis, ophthalmoparesis, facial weakness, and
      asymmetrical limb involvement should raise the suspicion of the manifesting
      carrier state. Necklace fibers appear to be a highly sensitive and specific
      pathologic finding in such cases.

PMID- 29567350
TI  - Progressive fat replacement of muscle contributes to the disease mechanism of
      patients with single, large-scale deletions of mitochondrial DNA.
AB  - Muscle dysfunction in mitochondrial myopathy is predominantly caused by
      insufficient generation of energy. We hypothesise that structural changes in
      muscles could also contribute to their pathophysiology. The aims of this study
      were to determine fat fractions and strength in selected muscles in patients with
      chronic progressive external ophthalmoplegia (CPEO), and compare progression of
      muscle fat fraction with age in individuals with CPEO vs. healthy controls and
      patients with the m.3243A>G mutation of mitochondrial DNA (mtDNA). Seventeen
      patients with CPEO and single large-scale deletions of mtDNA, 52 healthy
      controls, and 12 patients carrying the m.3243A>G mtDNA mutation were included.
      Muscle fat fractions were measured from cross-sections of paraspinal and leg
      muscles. Peak muscle strength was assessed from a static dynamometer. There was a
      direct correlation between age and fat fraction in all muscle groups in CPEO
      patients and healthy controls (p < 0.05). Analysis of covariance showed a higher
      progression rate of fat replacement in CPEO patients vs. healthy controls in
      studied muscle groups (p < 0.05). Patients with the m.3243A>G mutation had slower
      progression rates of fat replacement. Muscle strength decreased with increasing
      muscular fat fraction in CPEO patients, no correlation was seen in other groups.
      This indicates that structural muscle changes contribute to the phenotype of
      older patients affected by CPEO and large-scale deletions. It should therefore be
      considered, along with known energy deficiencies, as the cause of exercise
      intolerance.

PMID- 29567351
TI  - Interatrial block to predict atrial fibrillation in myotonic dystrophy type 1.
AB  - Paroxysmal atrial fibrillation frequently occurs in Myotonic dystrophy type 1
      (DM1) patients. Interatrial block is recognized as predictor of atrial
      arrhythmias, particularly atrial fibrillation (AF). The aim of this study was to
      evaluate the role of interatrial block in predicting the onset of atrial
      fibrillation during 2-year follow-up in DM1 patients who underwent pacemaker
      implantation for conduction system disorders. The study prospectively enrolled 70
      DM1 patients (aged 36-69; 31 M) who underwent pacemaker implantation for cardiac
      rhythm abnormalities in accordance with the current guidelines. All DM1 patients
      underwent 12-lead surface ECG, 2D color Doppler echocardiogram and device
      interrogation at implantation, one month after and every six months thereafter
      for a minimum of 2-year follow-up. 12-lead surface ECGs were analyzed to diagnose
      interatrial block (IAB), defined as a P-wave duration >=120 ms without (partial
      IAB) or with (advanced IAB) biphasic morphology (+/-) in the inferior leads.
      Device interrogation was performed to evaluate the development of new onset
      atrial high rate electrograms compatible with paroxysmal atrial fibrillation
      episodes. Interatrial block was detected in 22 patients (31.4%): 18 partial
      (25.7%) and 4 advanced (5.7%). During follow-up, AF episodes were detected in 18
      DM1 patients (25.7%). The study population was divided into 2 groups according to
      the presence of AF (AF+ Group vs AF- Group). The AF+ Group was older and showed
      higher prevalence of IAB than the AF- Group. IAB was found to be independent
      predictor of AF in DM1 population (P < 0.001). A cut-off value of 121 ms for IAB
      had a sensitivity of 83.3% and specificity of 90.3% in identifying DM1 patients
      at high risk of developing AF. Interatrial block represents an independent
      predictor of AF occurrence in our DM1 population with conduction disturbances who
      had previously undergone pacemaker implantation.

PMID- 29567352
TI  - Mechanical forces in skin disorders.
AB  - Mechanical forces are known to regulate homeostasis of the skin and play a role
      in the pathogenesis of skin diseases. The epidermis consists of keratinocytes
      that are tightly adhered to each other by cell junctions. Defects in keratins or
      desmosomal/hemidesmosomal proteins lead to the attenuation of mechanical strength
      and formation of intraepidermal blisters in the case of epidermolysis bullosa
      simplex. The dermis is rich in extracellular matrix, especially collagen, and
      provides the majority of tensile force in the skin. Keloid and hypertrophic scar,
      which is the result of over-production of collagen by fibroblasts during the
      wound healing, are associated with extrinsic tensile forces and changes of
      intrinsic mechanical properties of the cell. Increasing evidences shows that
      stiffness of the skin environment determines the regenerative ability during
      wound healing process. Mechanotransduction pathways are also involved in the
      morphogenesis and cyclic growth of hair follicles. The development of
      androgenetic alopecia is correlated to tensile forces generated by the fibrous
      tissue underlying the scalp. Acral melanoma predominantly occurs in the weight
      bearing area of the foot suggesting the role of mechanical stress. Increased
      dermal stiffness from fibrosis might be the cause of recessive dystrophic
      epidermolysis bullosa associated squamous cell carcinoma. Strategies to change
      the mechanical forces or modify the mechanotransduction signals may lead to a new
      way to treat skin diseases and promote skin regeneration.

PMID- 29567353
TI  - Proton pumping by cytochrome c oxidase - A 40 year anniversary.
AB  - Cytochrome c oxidase is a remarkable energy transducer that seems to work almost
      purely by Coulombic principles without the need for significant protein
      conformational changes. In recent years it has become possible to follow key
      partial reactions of the catalytic cycle in real time, both with respect to
      electron and proton movements. These experiments have largely set the stage for
      the proton pump mechanism. The structures of the catalytic binuclear heme-copper
      site that is common to the huge family of heme-copper oxidases, are today well
      understood throughout the catalytic cycle of oxygen reduction to water based on
      both spectroscopic studies and quantum chemical calculations. Here, we briefly
      review this progress, and add some recent details into how the proton pump
      mechanism is protected from failure by leakage.

PMID- 29567355
TI  - Hepatitis B vaccine nonresponders: Possible mechanisms and solutions.
AB  - OBJECTIVE: Hepatitis B (HBV) is a viral illness that chronically infects 240
      million people worldwide, leads to liver disease, and increases risk of
      hepatocellular carcinoma. The HBV vaccine has decreased HBV infection, and it and
      the human papilloma virus vaccine are the only vaccines that prevent cancer.
      Despite the effectiveness of the HBV vaccine, some populations do not develop
      protective responses. The risk groups for poor response include those with
      immunosuppression or dialysis-dependent, end-stage renal disease. Five percent of
      normal people do not have a response. These subjects are deemed HBV
      "nonresponders." Multiple strategies to improve the immunogenicity of the HBV
      vaccine are currently being pursued, including vaccine adjuvants, recombinant
      vaccines, and immune enhancement via up-regulation of dendritic cells. DATA
      SOURCES: PubMed was searched for peer-reviewed publications published from
      January 1980 to September 2017. STUDY SELECTIONS: Studies retrieved for inclusion
      summarized potential mechanisms behind HBV vaccine nonresponsiveness and
      potential solutions. RESULTS: The mechanisms behind HBV vaccine nonresponsiveness
      vary between each subject population. Many current and future strategies may
      provide protective immunity against HBV in each of these populations. CONCLUSION:
      This review provides a background on the immunology of HBV infection, the
      possible immunologic mechanisms to explain HBV vaccine nonresponsiveness, current
      research aimed at improving vaccine effectiveness, and possible future approaches
      for providing nonresponders protection from HBV.

PMID- 29567354
TI  - Consequences of cytochrome c oxidase assembly defects for the yeast stationary
      phase.
AB  - The assembly of cytochrome c oxidase (COX) is essential for a functional
      mitochondrial respiratory chain, although the consequences of a loss of assembled
      COX at yeast stationary phase, an excellent model for terminally differentiated
      cells in humans, remain largely unexamined. In this study, we show that a wild
      type respiratory competent yeast strain at stationary phase is characterized by a
      decreased oxidative capacity, as seen by a reduction in the amount of assembled
      COX and by a decrease in protein levels of several COX assembly factors. In
      contrast, loss of assembled COX results in the decreased abundance of many
      mitochondrial proteins at stationary phase, which is likely due to decreased
      membrane potential and changes in mitophagy. In addition to an altered
      mitochondrial proteome, COX assembly mutants display unexpected changes in
      markers of cellular oxidative stress at stationary phase. Our results suggest
      that mitochondria may not be a major source of reactive oxygen species at
      stationary phase in cells lacking an intact respiratory chain.

PMID- 29567356
TI  - Anaphylaxis care guidelines and the effect on health care resource use in the
      United States.

PMID- 29567357
TI  - Self-reported adverse reactions associated with mycoprotein (Quorn-brand)
      containing foods.
AB  - BACKGROUND: Mycoprotein, which is produced by a mold and is the basis of Quorn
      brand meat substitutes, is a novel cause of allergic and gastrointestinal
      reactions, but little information has been available on its associated
      symptomatology. OBJECTIVE: To describe the nature and frequency of adverse
      reactions to mycoprotein. METHODS: Self-reports of adverse reactions to
      mycoprotein were collected via a Web-based questionnaire
      (www.quorncomplaints.org) and then analyzed. RESULTS: Analysis of 1,752 adverse
      reactions found that Quorn products caused allergic and gastrointestinal
      symptoms, with some people experiencing both. Allergic reactions, including
      urticaria and anaphylaxis, occurred within 4 hours of consumption in 312 people.
      Of those reactions, 45.8%, 1 fatal, began within 1 hour of exposure. Of those 312
      individuals, 188 (60.3%) reported repeated reactions after repeated consumption
      of Quorn, and 2 people experienced 8 reactions (13 people did not say whether
      they experienced more than 1 reaction). Quorn foods caused gastrointestinal
      symptoms, including emesis and diarrhea, within 8 hours of consumption in 1,692
      people. Of the gastrointestinal symptoms, 66.6% occurred 46 to 180 minutes after
      consumption of the products. Symptoms ranged from mild nausea to emesis severe
      enough to warrant medical attention. CONCLUSION: Mycoprotein may be causing
      numerous and sometimes life-threatening allergic and gastrointestinal reactions.
      The acceptance in the food supply of this nonessential ingredient deserves
      reconsideration.

PMID- 29567358
TI  - Effect of short-term liver X receptor activation on epidermal barrier features in
      mild to moderate atopic dermatitis: A randomized controlled trial.
AB  - BACKGROUND: Liver X receptors (LXRs) are involved in maintaining epidermal
      barrier and suppressing inflammatory responses in model systems. The LXR agonist
      VTP-38543 showed promising results in improving barrier function and inflammatory
      responses in model systems. OBJECTIVE: To assess the safety, tolerability,
      cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in
      adults with mild to moderate atopic dermatitis (AD). METHODS: A total of 104
      ambulatory patients with mild to moderate AD were enrolled in this randomized,
      double-blind, vehicle-controlled trial between December 2015 and September 2016.
      VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was
      applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy
      specimens were obtained from a subset of 33 patients. Changes in SCORing of
      Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global
      Assessment, and tissue biomarkers (by real-time polymerase chain reaction and
      immunostaining) were evaluated. RESULTS: Topical VTP-38543 was safe and well
      tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of
      epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid
      (adenosine triphosphate-binding cassette subfamily G member 1 and sterol
      regulatory element binding protein 1c, P < .01) measures and reduced epidermal
      hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly
      suppressed cellular infiltrates and down-regulated mRNA expression of several
      TH17/TH22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and
      innate immunity (interleukin 6) markers. CONCLUSION: Topical VTP-38543 is safe
      and well tolerated. Its application led to improvement in barrier differentiation
      and lipids. Longer-term studies are needed to clarify whether a barrier-based
      approach can induce meaningful suppression of immune abnormalities. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT02655679.

PMID- 29567359
TI  - Validity and responsiveness of the Urticaria Activity and Impact Measure: A new
      patient-reported tool.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU), also known as chronic idiopathic
      urticaria, may produce hives, itch, and angioedema. The Urticaria Activity and
      Impact Measure (U-AIM) is a newly developed 9-item patient-reported measure
      designed for use in routine clinical practice to assess CSU activity and impact
      during the previous 7 days. OBJECTIVE: To evaluate validity, responsiveness, and
      clinically meaningful change of the U-AIM. METHODS: Data from a 24-week, open
      label, single-arm period of a randomized, placebo-controlled study of omalizumab
      were used to assess the psychometric properties of U-AIM items for itch, hives,
      and angioedema. RESULTS: A total of 206 patients (75% female; mean age, 44.6
      years) were enrolled. At baseline, U-AIM results included prevalent severe itch
      (55%) and more than 12 hives (67%), angioedema (15%), and bother by itch (84%),
      hives (84%), and angioedema (49%). The Urticaria Patient Daily Diary (UPDD) mean
      weekly scores were 15.4 (itch severity), 16.8 (number of hives), and 32.2
      (Urticaria Activity Score [UAS7]). At baseline, week 12, and week 24, U-AIM itch
      and hives items and UAS7 proxy scores (the sum of itch severity and number of
      hives during 7 days) demonstrated strong correlation coefficients with their
      corresponding measures from the UPDD (itch severity: 0.634-0.806; hives number:
      0.735-0.843; UAS7 proxy: 0.724-0.852). Changes in U-AIM scores differentiated
      patients by their perspective of symptom improvement. Meaningful change
      thresholds were established for itch severity and number of hives scores (range,
      0.8-1.0 for both) and the UAS7 proxy score (range, 10.5-12.5). CONCLUSION: The U
      AIM is valid and responsive to change and may help clinicians monitor CSU
      activity and track treatment effectiveness.

PMID- 29567360
TI  - Gastrointestinal metastasis from primary lung cancer. Case series and systematic
      literature review.
AB  - Aim of the present study is to report clinical characteristics and outcomes of
      patients treated in authors' hospital for GI metastasis from primary lung cancer,
      and to report and analyse the same data concerning patients retrieved from a
      systematic literature review. We performed a retrospective analysis of
      prospectively collected data, and a systematic review using the Meta-analysis Of
      Observational Studies in Epidemiology (MOOSE) guidelines. Ninety-one patients
      were included, 5 patients from the authors' hospital and 86 through PubMed
      database using the keywords "intestinal metastasis" AND "lung cancer". The median
      time between primary lung cancer diagnosis and GI metastasis diagnosis was 2
      months and the median overall survival was 4 months. This group of patients
      present a poor prognosis and the gold standard treatment is not defined. None of
      the reported treatments had a significant impact on survival.

PMID- 29567361
TI  - Metallic bezoar after suicide attempt.

PMID- 29567362
TI  - BRAF V600E mutation in papillary thyroid cancer and its effect on postoperative
      radioiodine (131I) therapy: Should we modify our therapeutic strategy?
AB  - INTRODUCTION: The BRAF V600E mutation in papillary thyroid cancer (PTC) has been
      associated with resistance to 131I. Our aim was to quantify the response to 131I
      after surgery in patients who had the mutation (BRAF+) and those who did not have
      the mutated gene (BRAF-). METHOD: A prospective cohort study was designed, from
      September 2015 to February 2016, which included patients with PTC receiving
      therapy after surgical treatment. Variables were described for age, gender,
      histology, tumor stage, thyroglobulin values before, 48h after and 6months after
      131I; absorbed dose and % activity on days 2 and 7 and elimination time. RESULTS:
      41 patients giving in total 67 thyroid remnants were included. 61% were BRAF+. In
      stagesiii and iv, 80% were BRAF+. In lateral resection, 100% were BRAF+. The
      number of nodes was higher in BRAF+: 3.4 vs 1.2 (P=.01). The classic variant was
      predominant in BRAF+ (91.7% vs 8.3%, P=.03). 85.7% vs 14.3% of BRAF+ had
      desmoplastic reaction (P=.02). The BRAF+ had a lower absorbed dose than the
      administered activity (5.4Gy/MBq vs 20Gy/MBq, P=.02); lower% activity with
      respect to the unit of mass at 2 (0.046%/g vs 0.103%/g, P=.02) and at 7days
      (0.006%/gr vs 0.034%/gr, P=.04) CONCLUSIONS: The mutation of the BRAF V600E gene
      is related with greater resistance to postoperative treatment with 131I since the
      onset of the disease.

PMID- 29567363
TI  - Screening of stationary phase selectivities for global lipid profiling by
      ultrahigh performance supercritical fluid chromatography.
AB  - The performance of seven sub-2-MUm particle packed columns (2-picolylamine, 2
      PIC; charged surface hybrid fluoro-phenyl, CSH-FP; high strength silica C18 SB,
      HSS-C18; diethylamine, DEA; 1-aminoanthracene, 1-AA; high density diol and
      ethylene bridged hybrid; BEH) was examined for lipid separation in ultra-high
      performance supercritical fluid chromatography (UHPSFC) coupled to quadrupole
      time-of-flight mass spectrometry. Based on the results of the column screening a
      method for profiling of multiple lipid species from the major lipid classes was
      developed. Stationary phases containing beta-hydroxy amines, i.e. 1-AA, DEA and 2
      PIC, yielded strong retention and poor peak shapes of zwitterionic lipids with
      primary amine groups, such as phosphatidylserines, phosphatidylethanolamines and
      its lyso forms. The BEH and HSS-C18 columns showed strong retention of polar and
      nonpolar lipids, respectively. The Diol column retained the majority of major
      lipid classes and also produced symmetric peaks. In addition, this column also
      produced the highest resolution within and between major lipid classes. An
      injection solvent composed of methanol:chloroform (1:2, v:v) and the addition of
      20 mM ammonium formate in the mobile phase improved chromatographic separation
      and mass spectrometry detection in comparison to ammonium acetate or absence of
      additive. Finally, chromatographic and mass spectrometric parameters were
      optimized for the Diol column using a design of experiments approach. The
      separation mechanism on the Diol column depended on the lipid functionality and
      the length and degree of unsaturation of the acyl groups. The developed method
      could resolve 18 lipid classes and multiple lipids within each class, from blood
      serum and brain tissue in 11 min.

PMID- 29567364
TI  - Development of an analytical method for urocanic acid isomers in fish based on
      reactive extraction cleanup and chaotropic chromatography techniques.
AB  - Urocanic acid (UA), existing in trans- or cis-isoform, is of fairly recent
      interest to food researchers because of its potential public health hazards of
      scombrotoxicity and immunotoxicity, as well as associating with fish spoilage.
      This work is among the first efforts to study the analytical chemistry of UA in
      fish. With 0.6 M perchloric acid UA was extracted, and co-extracted fish matrix
      components were efficiently removed through a reactive extraction of UA. The
      optimum conditions for the reactive extraction, which allowed an 80% recovery of
      UA, were sample pH adjustment to 9, twice extractions with 32% (w/w) di (2
      ethylhexyl) phosphate in hexanol, and a back-extraction with 0.1 M hydrochloric
      acid at 1:1 phase ratio. A chaotropic hexafluorophosphate salt was added to
      acidic water-acetonitrile mobile phases to improve the reversed-phase
      chromatography of UA, which otherwise was poorly retained. Optimum separation
      conditions were obtained for fish samples and enabled a fast (10 min), convenient
      to-use chromatography that clearly outperforms cumbersome legacy ion-pair
      chromatography. Intended for routine use in our laboratory, the proposed method
      passed an in-house validation test for linearity, matrix effect (on reactive
      extraction), accuracy, precision, and detectability.

PMID- 29567365
TI  - Enzyme assay for d-amino acid oxidase using optically gated capillary
      electrophoresis-laser induced fluorescence detection.
AB  - Because d-amino acids (AAs) play an essential role in the regulation of many
      processes in living cells, detection of D-AAs and assay of d-amino acid oxidase
      (DAAO) activity are of vital importance in bioanalytical science. However, the
      reliability and accuracy of DAAO assays could be interfered due to the facts that
      DAAO presents broad substrate activity towards different D-AAs and there could be
      abundant L-AA enantiomers in biological samples. In this study we presented the
      first application of optically gated capillary electrophoresis with LIF detection
      (OGCE-LIF) for efficient assay of DAAO activity. High repeatability of the OGCE
      LIF assay of amino acids (AAs) was achieved with relative standard deviation
      (RSD) (n = 15) less than 1.5% and 2.7% for migration time and peak height,
      respectively. Under the optimal OGCE-LIF conditions, five pairs of D/L-AA
      enantiomers were efficiently separated in less than 1 min with low limit of
      detection of 1.3 MUM. Enzymatic assays of DAAO were successfully achieved by
      detection the substrate consumption with OGCE-LIF, for either single or mixed AA
      substrates. Kinetic analysis of the parallel oxidation reactions of two different
      substrates was performed, which was in good agreement with the experimental
      results. Our study indicates OGCE-LIF can perform rapid and efficient separation
      of mixed pairs of AA enantiomers and is a promising method for quantitatively
      assaying DAAO catalyzed reaction with the presence of L-AA enantiomers in the
      sample. Our study would pave the way for accurate determination of D-AAs and DAAO
      enzymes in complicated biological samples.

PMID- 29567366
TI  - Reversed phase ion-pair chromatographic separation of sugar alcohols by
      complexation with molybdate ion.
AB  - In this study, we developed a simple and sensitive reversed phase ion-pair
      chromatographic method for the analysis of C4-C6 sugar alcohols. The method is
      based on the on-line complexation of sugar alcohols with molybdate ion. The
      resulting dinuclear anionic complexes can be separated on a reversed-phase C18
      column using tetrabutylammonium chloride as an ion-pairing reagent. The mobile
      phase (pH 3.1) consisted of 0.1 mM disodium molybdate, 1 mM hydrochloric acid and
      0.4 mM tetrabutylammonium chloride - 10% v/v methanol. By complexing with
      molybdate ion, sugar alcohols can be detected by their UV absorption at 247 nm
      with high resolution and sensitivity. The quantification limits of the examined
      sugar alcohols calculated at S/N = 10 were 0.1 mM for erythritol and xylitol and
      0.01 mM for arabitol, sorbitol, mannitol and dulcitol. The detector response was
      linear over three orders of magnitude of sugar alcohol concentration. The
      proposed method was successfully applied to measure sugar alcohols in health
      drinks, eyedrops and mouthwashes.

PMID- 29567367
TI  - With a simple calculation, the fraction of platelets remaining can be used to
      estimate the residual hemoglobin S percentage in sickle cell disease patients
      undergoing automated red blood cell exchange.
AB  - OBJECTIVES: Automated red blood cell exchange (RBX) is an important treatment for
      patients with sickle cell disease (SCD). Although not specifically targeted for
      removal, platelets (PLTs) are collected along with red blood cells during RBX. We
      sought to determine whether the pre- and post- RBX PLT counts could be used to
      derive the post-procedure hemoglobin S% (HgbS%). METHODS: Using the pre- and post
      RBX lab values of 59 SCD patients undergoing 112 RBX procedures over 1 year, we
      derived mathematical formulas which estimate the post-RBX HgbS% based on the pre
      RBX HgbS%, the pre- and post- RBX PLT, and a correction factor. RESULTS: For
      patients with pre-RBX HgbS > 40%, the mathematically derived post-RBX HgbS% was
      statistically indistinguishable from the measured post-RBX HgbS%. CONCLUSIONS:
      Using a simple formula, pre- and post-RBX platelet counts can provide a rapid
      approximation of the measured post-RBX HgbS% in patients with SCD.

PMID- 29567368
TI  - Efficacy of eculizumab in severe ADAMTS13-deficient thrombotic thrombocytopenic
      purpura (TTP) refractory to standard therapies.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathic hemolytic
      anemia (MAHA) defined by mechanical hemolytic anemia, severe thrombocytopenia,
      and systemic visceral ischemia due to systemic platelet-rich microthrombi. Forty
      percent of patients with autoimmune TTP experience one or multiple relapses.
      Patients with refractory TTP are currently managed by corticosteroids, twice
      daily PEX, and the anti-CD20 monoclonal antibody rituximab. Herein, we report two
      cases of severe TTP, refractory to those standard agents. On the basis of the
      fact that in cases of severe TTP the classical complement pathway is activated,
      and that the alternative pathway is also involved, both patients underwent
      eculizumab (anti-C5 monoclonal antibody) therapy. We observed prompt
      hematological and organ system responses to the eculizumab and the recovery of
      plasma ADAMTS-13 activity in both cases. Moreover, the fact that both patients
      discontinued eculizumab, maintaining the response, emphasizes the possibility of
      its usefulness for limited treatment periods. In conclusion, the diagnostic and
      therapeutic algorithm in TTP appears complicated by increasing evidence of
      complement involvement and the eculizumab seems to be a potential agent for
      refractory patients.

PMID- 29567369
TI  - Caring for patients with epilepsy: The many ways EEG is useful.

PMID- 29567370
TI  - Endoreplication: The Good, the Bad, and the Ugly.
AB  - To battle adverse internal and external conditions and maintain homeostasis,
      diploid organisms employ various cellular processes, such as proliferation and
      apoptosis. In some tissues, an alternative mechanism, endoreplication, is
      employed toward similar goals. Endoreplication is an evolutionarily conserved
      cell cycle program during which cells replicate their genomes without division,
      resulting in polyploid cells. Importantly, endoreplication is reported to be
      indispensable for normal development and organ formation across various
      organisms, from fungi to humans. In recent years, more attention has been drawn
      to delineating its connections to wound healing and tumorigenesis. In this
      Review, we discuss mechanisms of endoreplication and polyploidization, their
      essential and positive roles in normal development and tissue homeostasis, and
      the relationship between polyploidy and cancer.

PMID- 29567372
TI  - A six-microRNA signature predicts survival of patients with uterine corpus
      endometrial carcinoma.
AB  - Uterine corpus endometrial carcinoma (UCEC) is one of the most common female
      gynecological malignant tumors that threaten women health seriously. MicroRNAs
      (miRNAs) has been proved to play critical roles in tumor pathogenesis and
      malignant progression. In this study, we aimed to explore a novel signature of
      microRNA expression for predicting the overall survival (OS) of patients with
      UCEC. The genome-wide miRNA expression profiles and relevant clinical
      characteristics of 348 patients with UCEC were downloaded from the Cancer Genome
      Atlas (TCGA) data portal and analyzed comprehensively. A total of 144 miRNAs were
      confirmed to be expressed differentially in tumor tissues. Among them, 6 miRNAs
      (hsa-mir-15a.MIMAT0000068, hsa-mir-142.MIMAT0000433, hsa-mir-142.MIMAT0000434,
      hsa-mir-3170.MIMAT0015045, hsa-mir-1976.MIMAT0009451, and hsa-mir
      146a.MIMAT0000449) were validated to be significantly correlated with the OS of
      patients with UCEC. The risk indictor established by the 6-microRNA signature was
      proved be an independent prognostic factor (Hazard ratio = 0.391; 95% CI: 0.195
      0.783; P = 0.008). In conclusion, we identified miRNAs that were correlated with
      the occurrence and progression of UCEC and established a 6-microRNA expression
      signature as a predictor for the OS of patients with UCEC.

PMID- 29567371
TI  - A pilot study on immuno-psychiatry in the 22q11.2 deletion syndrome: A role for
      Th17 cells in psychosis?
AB  - BACKGROUND: A growing body of evidence supports a role for immune alterations in
      Schizophrenia Spectrum Disorders (SSD). A high prevalence (25-40%) of SSD has
      been found in patients with 22q11.2 deletion syndrome (22q11.2DS), which is known
      for T-cell deficits due to thymus hypoplasia. This study is the first to explore
      the association between the T-cell subsets and psychotic symptoms in adults with
      22q11.2DS. METHODS: 34 individuals (aged 19-38 yrs.) with 22q11.2DS and 34
      healthy age- and gender matched control individuals were included. FACS analysis
      of the blood samples was performed to define T-cell subsets. Ultra-high risk for
      psychosis or diagnosis of SSD was determined based on CAARMS interviews and DSM-5
      criteria for SSD. Positive psychotic symptom severity was measured based on the
      PANSS positive symptoms subscale. RESULTS: A partial T-cell immune deficiency in
      22q11.2DS patients was confirmed by significantly reduced percentages of
      circulating T and T-helper cells. Significantly higher percentages of
      inflammatory Th1, Th17, and memory T-helper cells were found in adults with
      22q11.2DS. Most importantly an increased Th17 percentage was found in adults with
      psychotic symptoms as compared to non-psychotic adults with 22q11.2DS, and Th17
      percentage were related to the presence of positive psychotic symptoms.
      CONCLUSIONS: Given the literature on the role of T cells and in particular of
      Th17 cells and IL-17 in hippocampus development, cognition and behavior, these
      results support the hypothesis for a role of Th17 cells in the development and/or
      regulation of psychotic symptoms in 22q11.2DS. This pilot study underlines the
      importance to further study the role of T-cell defects and of Th17 cells in the
      development of psychiatric symptoms. It also supports the possibility to use
      22q11.2DS as a model to study T-cell involvement in the development of SSD.

PMID- 29567373
TI  - Synthesis of novel laccase-biotitania biocatalysts for malachite green
      decolorization.
AB  - Biomimetic mineralization has emerged as a novel tool for generating excellent
      supports for enzyme stabilization. In this work, protamine was used to induce
      titanium (IV) bis(ammonium lactato) dihydroxide (Ti-BALDH) into titania
      nanoparticles. This biomimetic titanification process was adopted for laccase
      immobilization. Laccase-biotitania biocatalyst was prepared and the effect of
      different parameters (buffer solution, titania precursor concentration, protamine
      concentration, and enzyme loading) on the encapsulation efficiency and recovery
      of laccase were evaluated. Compared with free laccase, the thermal and pH
      stability of immobilized laccase were improved significantly. In addition,
      laccase loaded on titania was effective at enhancing its storage stability. After
      seven consecutive cycles, the immobilized laccase still retained 51% of its
      original activity. Finally, laccase-biotitania biocatalysts showed good
      performance on decolorization of malachite green (MG), which can be attributed to
      an adsorption and degradation effect. The intermediates of the MG degradation
      were identified by gas chromatography-mass spectrometry (GC-MS) analysis, and the
      most probable degradation pathway was proposed. This study provides deeper
      understanding of the laccase-biotitania particles as a fast biocatalyst for MG
      decolorization.

PMID- 29567374
TI  - Risk assessment of methylmercury based on internal exposure and fish and seafood
      consumption estimates in Taiwanese children.
AB  - Fish and seafood consumption is a major source of human exposure to methylmercury
      (MeHg). This study evaluated the potential health risk of MeHg in Taiwanese
      children from fish and seafood consumption using a toxicokinetic model, hazard
      quotients and hazard indices (HIs). Two biomonitoring programs provided an
      important resource for blood specimens for assessing MeHg exposure in human
      populations. For internal exposures, total mercury (THg) was measured as a
      biomarker of MeHg in whole blood (WB) and red blood cells using inductively
      coupled plasma mass spectrometry and cold-vapor atomic absorption spectroscopy,
      respectively. The THg concentrations were used to estimate MeHg concentrations.
      Consumption of fish and seafood was assessed using the National Food Consumption
      database in Taiwan, while mercury concentrations in edible fish and seafood were
      collected from published studies in Taiwan. Our results indicated that 1) the
      highest median THg (representing estimated MeHg) daily intakes were found to
      decrease with increasing age in children consuming saltwater fish for age groups
      0-3, 4-6, 7-12, and 13-18 years: 0.03 > 0.02 > 0.017 > 0.007 (MUg kg-BW-1 day-1);
      2) HI greater than one, based on WB-THg, was found in 28% of 4-6-year-old
      children and 3) internal exposure estimates based on WB-THg, though slightly
      higher, were comparable to those based on fish and seafood consumption. The
      results support the use of dietary intake estimates as surrogates for internal
      blood MeHg levels in Taiwanese children to assess their exposure.

PMID- 29567375
TI  - On the use of total aerobic spore bacteria to make treatment decisions due to
      Cryptosporidium risk at public water system wells.
AB  - Spore reduction can be used as a surrogate measure of Cryptosporidium natural
      filtration efficiency. Estimates of log10 (log) reduction were derived from spore
      measurements in paired surface and well water samples in Casper Wyoming and
      Kearney Nebraska. We found that these data were suitable for testing the
      hypothesis (H0) that the average reduction at each site was 2 log or less, using
      a one-sided Student's t-test. After establishing data quality objectives for the
      test (expressed as tolerable Type I and Type II error rates), we evaluated the
      test's performance as a function of the (a) true log reduction, (b) number of
      paired samples assayed and (c) variance of observed log reductions. We found that
      36 paired spore samples are sufficient to achieve the objectives over a wide
      range of variance, including the variances observed in the two data sets. We also
      explored the feasibility of using smaller numbers of paired spore samples to
      supplement bioparticle counts for screening purposes in alluvial aquifers, to
      differentiate wells with large volume surface water induced recharge from wells
      with negligible surface water induced recharge. With key assumptions, we propose
      a normal statistical test of the same hypothesis (H0), but with different
      performance objectives. As few as six paired spore samples appear adequate as a
      screening metric to supplement bioparticle counts to differentiate wells in
      alluvial aquifers with large volume surface water induced recharge. For the case
      when all available information (including failure to reject H0 based on the
      limited paired spore data) leads to the conclusion that wells have large surface
      water induced recharge, we recommend further evaluation using additional paired
      biweekly spore samples.

PMID- 29567377
TI  - Corrigendum to "Inhibition of protein phosphatase 5 suppresses non-small cell
      lung cancer through AMP-activated kinase activation" [Lung Cancer 112, (October)
      (2017) 81-89].

PMID- 29567378
TI  - Appraisal of Clinical Practice Guideline: Exercise for people with cancer.

PMID- 29567379
TI  - Clinimetrics: Tampa Scale for Kinesiophobia.

PMID- 29567376
TI  - The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition
      across 21 sites.
AB  - The ABCD study is recruiting and following the brain development and health of
      over 10,000 9-10 year olds through adolescence. The imaging component of the
      study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and
      the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were
      selected, optimized and harmonized across all 21 sites to measure brain structure
      and function relevant to adolescent development and addiction. This article
      provides an overview of the imaging procedures of the ABCD study, the basis for
      their selection and preliminary quality assurance and results that provide
      evidence for the feasibility and age-appropriateness of procedures and
      generalizability of findings to the existent literature.

PMID- 29567380
TI  - Critically Appraised Papers: In people with chronic obstructive pulmonary
      disease, home-based pulmonary rehabilitation produces similar results to a
      hospital-based outpatient program [commentary].

PMID- 29567381
TI  - Media: Home exercise programs made effortless using the PhysioTherapy eXercises
      patient app.

PMID- 29567383
TI  - Eventual re-vitrification or storage in liquid nitrogen vapor does not jeopardize
      the practical handling and transport of vitrified pig embryos.
AB  - This study aimed (1) to evaluate the in vitro post-warming survival of porcine
      embryos after re-vitrification and (2) to assess the efficacy of transport of
      embryos in dry shipper (DS) in maintaining the viability and quality of vitrified
      embryos for a 3-day period. Embryos at the compacted or cavitating morula (CCM)
      and unhatched blastocyst (UBL) stages were surgically obtained from weaned,
      crossbred sows. In the first experiment, more than 85% of the embryos survived an
      initial vitrification and warming and achieved comparable survival rates to those
      of their fresh counterparts. In contrast, those embryos subjected to a second
      vitrification and warming had clearly lower survival rates (60% and 64% for re
      vitrified embryos from the CCM and UBL groups, respectively) compared to the
      survival rates of the initial vitrification and fresh control groups (P < 0.01).
      Hatching rates were similar in re-vitrified blastocysts derived from vitrified
      CCMs and fresh control groups (50.8% and 55.3%, respectively). However,
      differences (P < 0.01) in hatching rates were recorded in re-vitrified
      blastocysts derived from vitrified UBLs and fresh control blastocysts (14.7% and
      90.0%, respectively). In the second experiment, vitrified embryos were stored in
      a liquid nitrogen tank for one month. Then, the straws containing the embryos
      were transferred to a DS (DS group) or to another liquid nitrogen tank (control
      group) for an additional three days. Embryos from the DS and control groups had
      similar survival and hatching rates, regardless of the embryonic stage
      considered. The DS storage of CCMs and UBLs did not affect their development
      after culturing, including total cell numbers, compared to the control, although
      their apoptotic index was slightly higher (P < 0.05), regardless of the
      developmental stage. In conclusion, although re-vitrification negatively affects
      embryo survival, this study demonstrated that >60% of vitrified embryos could be
      successfully re-vitrified and re-warmed. The present study also showed the
      effectiveness of the DS for the storage of vitrified porcine CCMs and UBLs for at
      least three 3 days.

PMID- 29567382
TI  - Effect of short- and medium-term toxicity of doxorubicin on spermatogenesis in
      adult Wistar rats.
AB  - Doxorubicin (DXR) is a widely used chemotherapeutic anticancer agent that has
      potent activity against several solid and non-solid human malignant tumors,
      including childhood malignancies. However, DXR has serious toxic effects on
      tissues with rapid cell cycles, such as myeloid and lymphatic tissues, intestinal
      mucosa, testes and ovaries. In the present study, the short- and medium-term
      toxic effects of DXR on the reproductive system of male Wistar rats were
      evaluated using morphometric and stereological tools to quantify damage to the
      seminiferous epithelium. Adult male Wistar rats were treated with dose of 7.5
      mg/kg of DXR and were sacrificed at seven, 14, 21 and 28 days after treatment.
      The testes were fixed in glutaraldehyde solution, routinely processed and
      embedded in plastic for evaluation under a light microscope. A significant
      reduction in testis weight was found as a result of massive germ cell apoptosis.
      Differences in comparison to the control group were found in the relative
      frequency of all stages of the seminiferous epithelium cycle, with significant
      differences for stages VIII-XI. Apoptosis significantly decreased the number of
      pachytene spermatocytes in the stages evaluated (I, II-III and VIII) at seven and
      14 days. At 21 and 28 days after treatment, the testes exhibited the massive loss
      of germ cells that resulted in a missing cell layer. Moreover, reductions in the
      height of seminiferous tubules, tubular diameter and tubular compartment as well
      as an increase in the intertubular compartment were found in the period studied.

PMID- 29567384
TI  - Chlorin Nanoparticles for Tissue Diagnostics and Photodynamic Therapy.
AB  - BACKGROUND: Organic crystalline nanoparticles (NPs) are not fluorescent due to
      the crystalline structure of the flat molecules organized in layers. In earlier
      experiments with Aluminum Phthalocyanine (AlPc)-derived NPs, the preferential
      uptake and dissolution by macrophages was demonstrated [3]. Therefore, inflamed
      tissue or cancer tissue with accumulated macrophages may exhibit specific
      fluorescence in contrast to healthy tissue which does not fluoresce. The present
      study addresses the photobiological effects of NP generated from Temoporfin
      (mTHPC), a clinically utilized photosensitizer belonging to the chlorin family.
      METHODS: In-vitro investigations addressing uptake, dissolution and phototoxicity
      of mTHPC NP vs. the liposomal mTHPC formulation Foslip were performed using
      J774A.1 macrophages and L929 fibroblasts. For total NP uptake analysis, the cells
      were lysed, the nanoparticles dissolved and the fluorescence quantified. The
      intracellular molecular dissolution was measured by flow cytometry. Fluorescence
      microscopy served for controlling intracellular localization of the dissolved
      fluorescing molecules. Reaction mechanisms after PDT (mitochondrial activity,
      apoptosis) were analyzed using fluorescent markers in cell-based assays and flow
      cytometry. RESULTS: Organic crystalline NP of different size were produced from
      mTHPC raw material. NP were internalized more efficiently in J774A.1 macrophages
      when compared to L929 fibroblasts, whereas uptake and fluorescence of Foslip was
      similar between the cell lines. NP dissolution correlated with internalization
      levels for larger particles in the range of 200-500 nm. Smaller particles (45 nm
      in diameter) were taken up at high levels in macrophages, but were not dissolved
      efficiently, resulting in comparatively low intracellular fluorescence. Whereas
      Foslip was predominantly localized in membranes, NP-mediated fluorescence also co
      localized with acidic vesicles, suggesting endocytosis/phagocytosis as a major
      uptake mechanism. In macrophages, phototoxicity of NPs was stronger than in
      fibroblasts, even exceeding Foslip when administered in identical amounts. In
      both cell lines, phototoxicity correlated with mitochondrial depolarization and
      enhanced activation of caspase 3. CONCLUSIONS: Due to their preferential
      uptake/dissolution in macrophages, mTHPC NP may have potential for the diagnosis
      and photodynamic treatment of macrophage-associated disorders such as
      inflammation and cancer.

PMID- 29567385
TI  - [A structured case analysis from the Critical Incident Reporting System of the
      German Medical Association and the National Association of Statutory Health
      Insurance Physicians].
AB  - BACKGROUND: Reporting systems for near misses are necessary to improve patient
      safety. In Germany, different systems are publicly available on both a national
      and regional level or as systems related to various medical domains. In contrast
      with the British Registry, our reporting systems still lack systematic
      evaluation. Using the Open-Task-Process Model (OPT model) one case of CIRSmedical
      (www.cirsmedical.de) was selected for a systematic analysis. METHOD: Case 148384
      reports on a patient with a tentative diagnosis of pulmonary embolism with an
      oxygen saturation of 71 %. The attending physician was ordered to leave the
      patient to participate in the daily team meeting. After 40minutes, the nurses
      transferred the patient from the emergency department to the ICU. The OPT model
      systematically checks the properties of all tasks in a given process and matches
      them to requirements or solving capacities of the task. RESULTS: The analysis
      manifests some structural problems: Although the case was not very difficult
      (high priority, but a frequent problem), the solving capacities were not adequate
      in order to avoid errors. Since the physician left the patient, the loyalty
      toward medical standards and the team error correction activity were low. The
      team did not intervene to prevent the doctor from leaving his patient.
      CONCLUSION: The OPT model allows for the analysis of both single cases and
      complete data sets of CIR systems and is able to disclose structural problems of
      clinical management.

PMID- 29567386
TI  - The Grueneberg olfactory organ neuroepithelium recovers after injury.
AB  - The Grueneberg organ (also termed Grueneberg ganglion) is an olfactory subsystem
      at the rostral nasal septum of rodents, and has been suggested to exist also in
      humans. Grueneberg organ neurons respond to coldness and alarm pheromones, but
      the anatomical arrangement and regenerative capacity are not fully characterised.
      We examined the relationship between the glia and the neurons using crosses of
      two transgenic mouse lines, S100beta-DsRed and OMP-ZsGreen, to visualise
      olfactory ensheathing cells (OECs) and Grueneberg olfactory neurons,
      respectively. Within the epithelium, Grueneberg organ OECs were in direct contact
      with Grueneberg organ neuron cell bodies. Individual axons from the neurons
      initially grew over the surface of the OECs before forming larger fascicles
      consisting of numerous axons and OECs. Considering the location of the Grueneberg
      organ so close to the external environment, it may be that the Grueneberg neurons
      are likely to be subject to damage suggesting that as in other olfactory regions
      there is a capacity for recovery after injury. Here, we used a well characterised
      model of olfactory nervous system injury, unilateral bulbectomy, to determine
      whether Grueneberg organ neurons degenerate after injury. We found that
      Grueneberg organ neurons degenerated in response to the axotomy, yet by 11 days
      post injury neurons and/or axons were detected again within the epithelium. Our
      results demonstrate that while Grueneberg organ neurons and glia have a distinct
      relationship in the epithelium, they have largely similar characteristics to that
      of the main olfactory neurons and glia.

PMID- 29567387
TI  - The spatial molecular pattern of integrin recognition sites and their
      immobilization to colloidal nanobeads determine alpha2beta1 integrin-dependent
      platelet activation.
AB  - Collagen, a strong platelet activator, is recognized by integrin alpha2beta1 and
      GPVI. It induces aggregation, if added to suspended platelets, or platelet
      adhesion if immobilized to a surface. The recombinant non-prolylhydroxylated mini
      collagen FC3 triple helix containing one alpha2beta1 integrin binding site is a
      tool to specifically study how alpha2beta1 integrin activates platelet. Whereas
      soluble FC3 monomers antagonistically block collagen-induced platelet activation,
      immobilization of several FC3 molecules to an interface or to colloidal nanobeads
      determines the agonistic action of FC3. Nanopatterning of FC3 reveals that
      intermolecular distances below 64 nm between alpha2beta1 integrin binding sites
      trigger signaling through dot-like clusters of alpha2beta1 integrin, which are
      visible in high resolution microscopy with dSTORM. Upon signaling, these integrin
      clusters increase in numbers per platelet, but retain their individual size.
      Immobilization of several FC3 to 100 nm-sized nanobeads identifies alpha2beta1
      integrin-triggered signaling in platelets to occur at a twentyfold slower rate
      than collagen, which activates platelet in a fast integrative signaling via
      different platelet receptors. As compared to collagen stimulation, FC3-nanobead
      triggered signaling cause a significant stronger activation of the protein kinase
      BTK, a weak and dispensable activation of PDK1, as well as a distinct
      phosphorylation pattern of PDB/Akt.

PMID- 29567388
TI  - Inducing hair follicle neogenesis with secreted proteins enriched in embryonic
      skin.
AB  - Organ development is a sophisticated process of self-organization. However,
      despite growing understanding of the developmental mechanisms, little is known
      about how to reactivate them postnatally for regeneration. We found that
      treatment of adult non-hair fibroblasts with cell-free extract from embryonic
      skin conferred upon them the competency to regenerate hair follicles. Proteomics
      analysis identified three secreted proteins enriched in the embryonic skin,
      apolipoprotein-A1, galectin-1 and lumican that together were essential and
      sufficient to induce new hair follicles. These 3 proteins show a stage-specific
      co-enrichment in the perifolliculogenetic embryonic dermis. Mechanistically,
      exposure to embryonic skin extract or to the combination of the 3 proteins
      altered the gene expression to an inductive hair follicle dermal papilla
      fibroblast-like profile and activated Igf and Wnt signaling, which are crucial
      for the regeneration process. Therefore, a cocktail of organ-specific
      extracellular proteins from the embryonic environment can render adult cells
      competent to re-engage in developmental interactions for organ neogenesis.
      Identification of factors that recreate the extracellular context of respective
      developing tissues can become an important strategy to promote regeneration in
      adult organs.

PMID- 29567390
TI  - Relationship between selenoprotein P and selenocysteine lyase: Insights into
      selenium metabolism.
AB  - Selenoprotein P (SelenoP) functions as a plasma transporter of selenium (Se) from
      liver to other tissues via incorporation into multiple selenocysteine (Sec)
      residues. Selenocysteine lyase (Scly) is an intracellular enzyme that decomposes
      Sec into selenide, providing Se for the synthesis of new selenoproteins. Both
      SelenoP and Scly are mostly produced by the liver. Previous studies demonstrated
      that male mice lacking SelenoP (SelenoP KO) or Scly (Scly KO) had increased or
      decreased total hepatic Se, respectively. While SelenoP regulation by Se is well
      studied, Scly regulation by Se has not been reported. We hypothesize that Scly is
      negatively regulated by Se levels, and that absence of SelenoP jeopardizes Scly
      dependent Se recycling. Using in vitro and in vivo models, we unveiled a tissue
      specific Se regulation of Scly gene expression. We also determined that SelenoP,
      a considered source of intracellular Se, affects Scly expression and activity in
      vitro but not in vivo, as in the absence of SelenoP, Scly levels and activity
      remain normal. We also showed that absence of SelenoP does not increase levels of
      transsulfuration pathway enzymes, which would result in available selenocompounds
      being decomposed by the actions of cystathionine gamma-lyase (CGL or CTH) and
      cystathionine beta-synthase (CBS). Instead, it affects levels of thioredoxin
      reductase 1 (Txnrd1), an enzyme that can reduce selenite to selenide to be used
      in selenoprotein production. This study evaluates a potential interplay between
      SelenoP and Scly, providing further insights into the regulation of selenium
      metabolism.

PMID- 29567391
TI  - Pro-fluorescent mitochondria-targeted real-time responsive redox probes
      synthesised from carboxy isoindoline nitroxides: Sensitive probes of
      mitochondrial redox status in cells.
AB  - Here we describe new fluorescent probes based on fluorescein and rhodamine that
      provide reversible, real-time insight into cellular redox status. The new probes
      incorporate bio-imaging relevant fluorophores derived from fluorescein and
      rhodamine linked with stable nitroxide radicals such that they cannot be cleaved,
      either spontaneously or enzymatically by cellular processes. Overall fluorescence
      emission is determined by reversible reduction and oxidation, hence the steady
      state emission intensity reflects the balance between redox potentials of
      critical redox couples within the cell. The permanent positive charge on the
      rhodamine-based probes leads to their rapid localisation within mitochondria in
      cells. Reduction and oxidation also leads to marked changes in the fluorophore
      lifetime, enabling monitoring by fluorescence lifetime imaging microscopy.
      Finally, we demonstrate that administration of a methyl ester version of the
      rhodamine-based probe can be used at concentrations as low as 5 nM to generate a
      readily detected response to redox stress within cells as analysed by flow
      cytometry.

PMID- 29567389
TI  - Polyphenol uses in biomaterials engineering.
AB  - Polyphenols are micronutrients obtained from diet that have been suggested to
      play an important role in health. The health benefits of polyphenols and their
      protective effects in food systems as antioxidant compounds are well known and
      have been extensively investigated. However, their functional roles as a
      "processing cofactor" in tissue engineering applications are less widely known.
      This review focuses on the functionality of polyphenols and their application in
      biomaterials. Polyphenols have been used to stabilize collagen and to improve its
      resistance to degradation in biological systems. Therefore, they have been
      proposed to improve the performance of biomedical devices used in cardiovascular
      systems by improving the mechanical properties of grafted heart valves, enhancing
      microcirculation through the relaxation of the arterial walls and improving the
      capillary blood flow and pressure resistance. Polyphenols have been found to
      stimulate bone formation, mineralization, as well as the proliferation,
      differentiation, and the survival of osteoblasts. These effects are brought about
      by the stimulatory effect of polyphenols on osteoblast cells and their protective
      effect against oxidative stress and inflammatory cytokines. In addition,
      polyphenols inhibit the differentiation of the osteoclast cells. Collectively,
      these actions lead to promote bone formation and to reduce bone resorption,
      respectively. Moreover, polyphenols can increase the cross-linking of dentine and
      hence its mechanical stability. Overall, polyphenols provide interesting
      properties that will stimulate further research in the bioengineering field.

PMID- 29567394
TI  - Consistent associations with beneficial bacteria in the seed endosphere of barley
      (Hordeum vulgare L.).
AB  - The importance of the plant microbiome for host fitness has led to the concept of
      the "plant holobiont". Seeds are reservoirs and vectors for beneficial microbes,
      which are very intimate partners of higher plants with the potential to connect
      plant generations. In this study, the endophytic seed microbiota of numerous
      barley samples, representing different cultivars, geographical sites and harvest
      years, was investigated. Cultivation-dependent and -independent analyses,
      microscopy, functional plate assays, greenhouse assays and functional prediction
      were used, with the aim of assessing the composition, stability and function of
      the barley seed endophytic bacterial microbiota. Associations were consistently
      detected in the seed endosphere with Paenibacillus, Pantoea and Pseudomonas spp.,
      which were able to colonize the root with a notable rhizocompetence after seed
      germination. In greenhouse assays, enrichment with these bacteria promoted barley
      growth, improved mineral nutrition and induced resistance against the fungal
      pathogen Blumeria graminis. We demonstrated here that barley, an important crop
      plant, was consistently associated with beneficial bacteria inside the seeds. The
      results have relevant implications for plant microbiome ecology and for the
      holobiont concept, as well as opening up new possibilities for research and
      application of seed endophytes as bioinoculants in sustainable agriculture.

PMID- 29567396
TI  - Advances in microfluidics for lipid nanoparticles and extracellular vesicles and
      applications in drug delivery systems.
AB  - Lipid-based nanobiomaterials as liposomes and lipid nanoparticles (LNPs) are the
      most widely used nanocarriers for drug delivery systems (DDSs). Extracellular
      vesicles (EVs) and exosomes are also expected to be applied as DDS nanocarriers.
      The performance of nanomedicines relies on their components such as lipids,
      targeting ligands, encapsulated DNA, encapsulated RNA, and drugs. Recently, the
      importance of the nanocarrier sizes smaller than 100nm is attracting attention as
      a means to improve nanomedicine performance. Microfluidics and lab-on-a chip
      technologies make it possible to produce size-controlled LNPs by a simple
      continuous flow process and to separate EVs from blood samples by using a surface
      marker, ligand, or electric charge or by making a mass or particle size
      discrimination. Here, we overview recent advances in microfluidic devices and
      techniques for liposomes, LNPs, and EVs and their applications for DDSs.

PMID- 29567392
TI  - Small-molecule luminescent probes for the detection of cellular oxidizing and
      nitrating species.
AB  - Reactive oxygen species (ROS) have been implicated in both pathogenic cellular
      damage events and physiological cellular redox signaling and regulation. To
      unravel the biological role of ROS, it is very important to be able to detect and
      identify the species involved. In this review, we introduce the reader to the
      methods of detection of ROS using luminescent (fluorescent, chemiluminescent, and
      bioluminescent) probes and discuss typical limitations of those probes. We review
      the most widely used probes, state-of-the-art assays, and the new, promising
      approaches for rigorous detection and identification of superoxide radical anion,
      hydrogen peroxide, and peroxynitrite. The combination of real-time monitoring of
      the dynamics of ROS in cells and the identification of the specific products
      formed from the probes will reveal the role of specific types of ROS in cellular
      function and dysfunction. Understanding the molecular mechanisms involving ROS
      may help with the development of new therapeutics for several diseases involving
      dysregulated cellular redox status.

PMID- 29567393
TI  - Ascorbic acid metabolism and functions: A comparison of plants and mammals.
AB  - Ascorbic acid is synthesised by eukaryotes, the known exceptions being primates
      and some other animal groups which have lost functional gulonolactone oxidase.
      Prokaryotes do not synthesise ascorbate and do not need an ascorbate supply, so
      the functions that are essential for mammals and plants are not required or are
      substituted by other compounds. The ability of ascorbate to donate electrons
      enables it to act as a free radical scavenger and to reduce higher oxidation
      states of iron to Fe2+. These reactions are the basis of its biological activity
      along with the relative stability of the resulting resonance stabilised
      monodehydroascorbate radical. The importance of these properties is emphasised by
      the evolution of at least three biosynthetic pathways and production of an
      ascorbate analogue, erythroascorbate, by fungi. The iron reducing activity of
      ascorbate maintains the reactive centre Fe2+ of 2-oxoglutarate-dependent
      dioxygenases (2-ODDs) thus preventing inactivation. These enzymes have diverse
      functions and, recently, the possibility that ascorbate status in mammals could
      influence 2-ODDs involved in histone and DNA demethylation thereby influencing
      stem cell differentiation and cancer has been uncovered. Ascorbate is involved in
      iron uptake and transport in plants and animals. While the above biochemical
      functions are shared between mammals and plants, ascorbate peroxidase (APX) is an
      enzyme family limited to plants and photosynthetic protists. It provides these
      organisms with increased capacity to remove H2O2 produced by photosynthetic
      electron transport and photorespiration. The Fe reducing activity of ascorbate
      enables hydroxyl radical production (pro-oxidant effect) and the reactivity of
      dehydroascorbate (DHA) and reaction of its degradation products with proteins
      (dehydroascorbylation and glycation) is potentially damaging. Ascorbate status
      influences gene expression in plants and mammals but at present there is little
      evidence that it acts as a specific signalling molecule. It most likely acts
      indirectly by influencing the redox state of thiols and 2-ODD activity. However,
      the possibility that dehydroascorbylation is a regulatory post-translational
      protein modification could be explored.

PMID- 29567397
TI  - Nanopharmaceuticals for wound healing - Lost in translation?
AB  - Today, many of the newly developed pharmaceuticals and medical devices take
      advantage of nanotechnology and with a rising incidence of chronic diseases such
      as diabetes and cardiovascular disease, the number of patients afflicted globally
      with non-healing wounds is growing. This has created a requirement for improved
      therapies and wound care. However, converting the strategies applied in early
      research into new products is still challenging. Many of them fail to comply with
      the market requirements. This review discusses the legal and scientific
      challenges in the design of nanomedicines for wound healing. Are they lost in
      translation or is there a new generation of therapeutics in the pipeline?

PMID- 29567398
TI  - Delivery systems of current biologicals for the treatment of chronic cutaneous
      wounds and severe burns.
AB  - While wound therapy remains a clinical challenge in current medical practice,
      much effort has focused on developing biological therapeutic approaches. This
      paper presents a comprehensive review of delivery systems for current biologicals
      for the treatment of chronic wounds and severe burns. The biologicals discussed
      here include proteins such as growth factors and gene modifying molecules, which
      may be delivered to wounds free, encapsulated, or released from living systems
      (cells, skin grafts or skin equivalents) or biomaterials. Advances in biomaterial
      science and technologies have enabled the synthesis of delivery systems such as
      scaffolds, hydrogels and nanoparticles, designed to not only allow spatially and
      temporally controlled release of biologicals, but to also emulate the natural
      extracellular matrix microenvironment. These technologies represent an attractive
      field for regenerative wound therapy, by offering more personalised and effective
      treatments.

PMID- 29567395
TI  - In situ forming injectable hydrogels for drug delivery and wound repair.
AB  - Hydrogels have been utilized in regenerative applications for many decades
      because of their biocompatibility and similarity in structure to the native
      extracellular matrix. Initially, these materials were formed outside of the
      patient and implanted using invasive surgical techniques. However, advances in
      synthetic chemistry and materials science have now provided researchers with a
      library of techniques whereby hydrogel formation can occur in situ upon delivery
      through standard needles. This provides an avenue to minimally invasively deliver
      therapeutic payloads, fill complex tissue defects, and induce the regeneration of
      damaged portions of the body. In this review, we highlight these injectable
      therapeutic hydrogel biomaterials in the context of drug delivery and tissue
      regeneration for skin wound repair.

PMID- 29567399
TI  - The safety, tolerability and pharmacokinetics of BI 409306, a novel and potent
      PDE9 inhibitor: Overview of three Phase I randomised trials in healthy
      volunteers.
AB  - Safety, tolerability and pharmacokinetics of BI 409306, a potent and selective
      phosphodiesterase 9A inhibitor, were assessed in healthy subjects in three Phase
      I, within-dose group, double-blind trials. Trial 1 randomised young and elderly
      subjects to receive BI 409306 25, 50, 100 mg, placebo once daily (OD) or BI
      409306 50 mg twice daily (young) for 14 days. Trial 2 randomised young poor
      metabolisers (PM) of cytochrome P450 isoform 2C19 (CYP2C19) and elderly subjects
      to receive BI 409306 25, 50 mg or placebo OD for 14 days. Trial 3 randomised
      Chinese and Japanese extensive metabolisers of CYP2C19 to receive single doses
      (SD) of BI 409306 25, 50, 100 mg or placebo and Chinese (PM) to SD of BI 409306
      100 mg or placebo (Part 1). Japanese PM received SD of BI 409306 100 mg or
      placebo (Day 1) followed by BI 409306 100 mg or placebo OD for 7 days after a 48
      hour washout period (Part 2). Reported adverse events (AE) were mild-to-moderate
      intensity and increased with BI 409306 dose. Eye disorders were most commonly
      reported (Trial 1: 40.0-41.7%, Trial 2: 29.2-37.5%, Trial 3: 18.2-66.7%) and
      increased with dose and systemic exposure. PM reported more AEs than other
      treatment groups, corresponding to higher systemic exposure to BI 409306.
      Systemic exposure to BI 409306 produced dose-dependent increases and was slightly
      greater in elderly versus young subgroups (Trial 1). Steady state was achieved by
      Day 2-3. Overall, BI 409306 demonstrated good safety, tolerability and minor
      accumulation after multiple dosing.

PMID- 29567400
TI  - Increased exploratory activity in rats with deficient sensorimotor gating: a
      study of schizophrenia-relevant symptoms with genetically heterogeneous NIH-HS
      and Roman rat strains.
AB  - Schizophrenia involves positive, negative and cognitive symptoms, as well as
      comorbidity with anxiety and obsessive-compulsive disorder. Prepulse inhibition
      (PPI) of the startle response is a measure of sensorimotor gating that is
      impaired in schizophrenia and animal models of the disease. Remarkably, impaired
      PPI has been related to other schizophrenia-like features in rodent models, such
      as cognitive deficits and hyperactivity. However, it remains to be investigated
      whether deficient PPI and increased exploratory activity are associated in
      genetically heterogeneous (outbred) naive animals. This study was undertaken to
      evaluate the relationships among PPI and other schizophrenia-related symptoms,
      such as augmented exploratory activity, anxiety and compulsivity in the
      genetically heterogeneous (outbred) NIH-HS rat stock (HS) and in the genetically
      selected inbred Roman High-Avoidance (RHA) and Low-avoidance (RLA) rats. Animals
      underwent the following tests: open-field (exploratory activity), elevated zero
      maze (anxiety-like behavior), marble burying (compulsive-like behavior), and PPI.
      Three groups of HS rats were formed according to their PPI scores, i.e. Low-PPI,
      Medium-PPI and High-PPI. The HS Low-PPI group displayed higher exploratory
      activity in the open-field than the HS Medium-PPI and HS High-PPI groups.
      Likewise, compared with their RLA counterparts, RHA rats exhibited lower PPI and
      more intense exploratory activity in the open-field test. Correlational and
      factorial analyses of the whole HS sample and the RHA/RLA data globally
      corroborated the results of the PPI-stratified HS subgroups. These data suggest
      that such a consistent association between impaired PPI and increased exploratory
      activity in outbred HS and inbred RHA/RLA rats is a relevant parameter that must
      be taken into account when modeling clusters of schizophrenia-relevant symptoms.

PMID- 29567401
TI  - A predator's response to a prey's deterrent signal changes with experience.
AB  - Prey signalling to predators is an attempt to divert or nullify an attack even
      before it occurs. If these signals are backed up by a potent defence, then the
      likelihood of the predators learning to avoid them is high. In species that use
      deceptive signalling, predators could learn to overcome such a display and
      diminish the efficacy of the display. We studied the effect of experience on the
      efficacy of tephritid fly displays against jumping spiders. We compared attacks
      on displaying flies, non-displaying flies, and two other prey species (a facile
      prey and a prey with a defence). Spiders were more likely to attack displaying
      flies over time. However, spiders that were familiar with the fly appearance but
      not display also increased their attack rates. We suggest that spiders attend to
      both components of the fly display, i.e. motion and appearance, but with motion
      cues taking priority.

PMID- 29567402
TI  - Suspiciousness in young minds: Convergent evidence from non-clinical, clinical
      and community twin samples.
AB  - BACKGROUND: We validated the Social Mistrust Scale (SMS) and utilized it to
      examine the structure, prevalence, and heritability of social mistrust in a large
      sample of Chinese children and adolescents. METHODS: In Study 1, a large sample
      of healthy twins (N=2094) aged 8 to 14years (M=10.27years, SD=2) completed the
      SMS. Structural equation modeling (SEM) was conducted to assess the structure of
      the SMS and to estimate the heritability of social mistrust in a sub-sample of
      twins (n=756 pairs). In Study 2, 32 adolescents with childhood-onset
      schizophrenia were compared with 34 healthy controls on levels of suspiciousness
      and clinical symptoms to examine the associations between the SMS and the
      Positive and Negative Syndrome Scale (PANSS). RESULTS: We found a three-factor
      structure for social mistrust (home, school, and general mistrust). Social
      mistrust was found to be moderately - heritable (19%-40%), with mistrust at home
      most strongly influenced by genetic factors. Compared with 11.76% of the healthy
      controls, 56.25% of the adolescents with early-onset schizophrenia exhibited very
      high levels of social mistrust on all three subscales of the SMS. The SMS
      exhibited good discriminant validity in distinguishing adolescents with childhood
      onset schizophrenia from healthy controls and showed associations with a broad
      range of symptoms assessed by the PANSS. CONCLUSIONS: Social mistrust assessed by
      the SMS may be heritable. The SMS demonstrates good discriminant validity with
      clinical diagnoses of schizophrenia. However, it seems to be correlated with
      multiple aspects of psychopathology in the schizophrenia group, rather than being
      specific to delusional ideation/paranoia.

PMID- 29567404
TI  - FIA-MS/MS determination of creatinine in urine samples undergoing butylation.
AB  - Flow injection analysis-tandem mass spectrometry has become widely used for
      analysis of many biomarkers in various biological matrices. To improve the
      sensitivity, the compounds are often determined as their butylesters. Since the
      concentration of urinary excreted compounds are generally reported after
      normalization to creatinine, the aim of this study was to investigate the
      possibility of creatinine determination in urine samples which underwent
      butylation. The impact of derivatization on urinary creatinine determination was
      investigated by measuring of underivatized and derivatized samples. The 10%
      creatine to creatinine conversion was observed during butylation, what above 700
      MUmol creatine/mmol creatinine caused significant creatinine overestimation. In
      that case, correction for creatine conversion rate was done. QC samples at six
      concentration levels were examined and precision and accuracy values fulfill the
      European Medicine Agency validation requirements. The elaborated method was
      applied for determination of creatinine in 41 real human urine samples.
      Determined creatinine concentrations were in the range of 0.27-22.3 mmol/L,
      linearity was confirmed within the concentration range of 0.27-31.7 mmol/L.
      Obtained results highly correlated with routinely used enzymatic assay for all
      tested samples and proposed method provide reliable determination of creatinine
      in butylated urine in a single run with butylesters of other analytes of
      interest.

PMID- 29567405
TI  - Phylogenetic analysis of cnidarian peroxiredoxins and stress-responsive
      expression in the estuarine sea anemone Nematostella vectensis.
AB  - Peroxiredoxins (PRXs) are a family of antioxidant enzymes present in all domains
      of life. To date, the diversity and function of peroxiredoxins within animals
      have only been studied in a few model species. Thus, we sought to characterize
      peroxiredoxin diversity in cnidarians and to gain insight into their function in
      one cnidarian-the sea anemone Nematostella vectensis. Phylogenetic analysis using
      all six known PRX subfamilies (PRX1-4, PRX5, PRX6, PRXQ/AHPE1, TPX, BCP-PRXQ)
      revealed that like bilaterians, cnidarians contain representatives from three
      subfamilies (PRX1-4, PRX5, PRX6). Within the PRX1-4 subfamily, cnidarian
      sequences fall into two clades: PRX4, and a cnidarian-specific clade, which we
      term CNID-PRX. This phylogenetic analysis demonstrates that the three PRX
      subfamilies present in Bilateria were also present in the last common ancestor of
      the Cnidaria and Bilateria, and further that diversification of the PRX1-4
      subfamily has occurred within the cnidarian lineage. We next examined the impact
      of decreased salinity, increased temperature, and peroxide exposure on the
      expression of four prx genes in N. vectensis (cnid-prx, prx4, prx5, and prx6).
      These genes exhibited unique expression patterns in response to these
      environmental stressors. Expression of prx4 decreased with initial exposure to
      elevated temperature, cnid-prx increased with exposure to elevated temperatures
      as well as with hydrogen peroxide exposure, and expression of all prxs
      transiently decreased with reduced salinity. Predicted subcellular localization
      patterns also varied among PRX proteins. Together these results provide evidence
      that peroxiredoxins in N. vectensis serve distinct physiological roles and lay a
      groundwork for understanding how peroxiredoxins mediate cnidarian developmental
      processes and environmental responses.

PMID- 29567403
TI  - Comparisons of schizotypal traits across 12 countries: Results from the
      International Consortium for Schizotypy Research.
AB  - BACKGROUND: Schizotypal traits are expressions of underlying vulnerability to
      psychotic disorders which have a potential impact on mental health status,
      neurocognition, quality of life, and daily functioning. To date, little research
      has examined epidemiologic landscape of schizotypal traits at the cross-national
      level. Our aim was to study the expression of schizotypal traits by sex, age, and
      country in a combined sample gathered from 12 countries. METHODS: A total of
      27,001 participants completed the Schizotypal Personality Questionnaire (SPQ).
      The mean age of participants was 22.12 (SD=6.28); 37.5% (n=10,126) were males.
      RESULTS: Schizotypal traits varied according to sex, age, and country. Females
      scored higher than males in the positive dimension, whereas males scored higher
      in the disorganization dimension. By age, a significant decrease in the positive
      schizotypal traits was observed. Epidemiological expression of schizotypal traits
      varied by country. Moreover, several interactions by sex, age, and country were
      found. CONCLUSIONS: This pattern is similar to those found in patients with
      psychosis and psychotic-like experiences. These findings provide new insights and
      the opportunity to explore the phenotypic expression of schizotypal traits at
      cross-national level.

PMID- 29567406
TI  - Utilization of nano-cryptomelane for the removal of cobalt, cesium and lead ions
      from multicomponent system: Kinetic and equilibrium studies.
AB  - Nano-cryptomelane was prepared and characterized using SEM with mapping, HRTEM,
      FT-IR spectra, thermal analysis and surface area. The diameter distribution of
      nano-cryptomelane was found to be 4-6 nm. Sorption performance of the prepared
      material was studied for the removal of Co2+, Cs+ and Pb2+ from a multi-system
      solution of equal molar ratio, 1:1:1. The sorption capacity of nano-cryptomelane
      was found to be 179.6, 442.6 and 716.9 mg/g for Co2+, Cs+ and Pb2+, respectively.
      The kinetic studies revealed that the sorption process obeys non-linear pseudo
      second-order model and is controlled by an intra-particle diffusion mechanism.
      The equilibrium isotherm investigations outlined that the extended Langmuir
      isotherm model fits the data reasonably well and it is more applicable than
      Freundlich multicomponent sorption isotherm. The value of diffusion coefficient
      for the three metal ions is in the order 10-17 m2/s which indicates the
      chemisorption nature of the process. The desorption percentage attains the
      maximum value (98.13%, 97.29 and 97.04 for lead, cesium and cobalt ions,
      respectively) using 0.7 mol/L of HNO3. This revealed that nano-cryptomelane can
      be regenerated and reused for farther sorption of Pb2+, Cs+ and Co2+ from
      wastewater.

PMID- 29567407
TI  - Using machine learning and quantum chemistry descriptors to predict the toxicity
      of ionic liquids.
AB  - Large-scale application of ionic liquids (ILs) hinges on the advancement of
      designable and eco-friendly nature. Research of the potential toxicity of ILs
      towards different organisms and trophic levels is insufficient. Quantitative
      structure-activity relationships (QSAR) model is applied to evaluate the toxicity
      of ILs towards the leukemia rat cell line (ICP-81). The structures of 57 cations
      and 21 anions were optimized by quantum chemistry. The electrostatic potential
      surface area (SEP) and charge distribution area (Ssigma-profile) descriptors are
      calculated and used to predict the toxicity of ILs. The performance and
      predictive aptitude of extreme learning machine (ELM) model are analyzed and
      compared with those of multiple linear regression (MLR) and support vector
      machine (SVM) models. The highest R2 and the lowest AARD% and RMSE of the
      training set, test set and total set for the ELM are observed, which validates
      the superior performance of the ELM than that of obtained by the MLR and SVM. The
      applicability domain of the model is assessed by the Williams plot.

PMID- 29567408
TI  - Probabilistic risk assessment of exposure to fluoride in most consumed brands of
      tea in the Middle East.
AB  - The aim of this study was to evaluate the fluoride concentration in seven most
      consumed brands of tea in the Middle East which was imported to Iran through
      Zabol County. In the present study, the health risk of exposure to fluoride was
      estimated using a probabilistic approach. Monte Carlo simulation and sensitivity
      analysis were applied to quantify uncertainties in risk estimation. The highest
      mean and 95th percentile of chronic daily intake (CDI) was observed for children
      group. Iranian tea and Kenya tea had maximum CDI and target hazard quotient (THQ)
      values among studied brands of tea which followed by Green tea, Taksetare tea,
      Ceylan tea, Red tea, and White tea. These result indicated that there were
      significant risks of exposure to fluoride in most of studied brands of tea for
      children (THQ>1). Sensitivity analysis showed that fluoride concentration and
      daily intake were the most influential variables in three exposed populations. In
      conclusion, the fluoride concentration in some studied brands of tea is high and
      it put children at risk risks of exposure to fluoride.

PMID- 29567409
TI  - Portuguese preschool children: Benefit (EPA+DHA and Se) and risk (MeHg)
      assessment through the consumption of selected fish species.
AB  - This study aimed to assess the risk-benefit balance associated to fish
      consumption by Portuguese preschool children. For this purpose, databases (from
      IPMA and literature) were mined and mathematically processed by a model based on
      the Extreme Value Theory assuming consumption scenarios. Eicosapentaenoic (EPA)
      and docosahexaenoic acid (DHA) and selenium (Se) and methylmercury (MeHg) were
      selected as critical components of fish, given their health impact and
      significant contents in some fish species. Assessment also took into account that
      Se may protect against MeHg toxicity. With exception of blue shark, Se Health
      Benefit Value (Se-HBV), was always positive (ranging between 3.3 and 14.9) and
      Se:MeHg ratio was always higher than one (3.8 to 32.3). It was also estimated
      that the deleterious effects of MeHg on children IQ were offset by the beneficial
      impact of EPA+DHA in fish except for grilled black scabbardfish consumed every
      day. Blue shark, regardless of the culinary treatment, yielded very high
      probabilities of exceeding MeHg TWI (higher than 84 % with a single weekly meal),
      thus raising serious concerns. EPA+DHA benefits were high in salmon regardless of
      culinary treatment (> 84 %). Fish consumption by children is advisable with
      exception of blue shark and boiled and grilled tuna.

PMID- 29567410
TI  - Person-centred care during prolonged weaning from mechanical ventilation, nurses'
      views: an interview study.
AB  - OBJECTIVE: To determine: 1) if the three elements of person-centred care
      (initiating, working and safeguarding the partnership) were present, and 2) to
      identify evidence of barriers to person-centred care during prolonged weaning
      from mechanical ventilation. RESEARCH METHODOLOGY: Secondary analysis of semi
      structured interviews with 19 critical care nurses using theoretical thematic
      analysis. SETTING: This study was conducted in three Swedish intensive care
      units, one in a regional hospital and two in a university hospital. FINDINGS:
      Three themes and nine subthemes related to person-centred care were identified.
      The three themes included: 1) 'finding a person behind the patient' related to
      the 'initiating the partnership' phase, 2) 'striving to restore patients sense of
      control' related to 'working the partnership' phase and 3) 'impact of patient
      involvement' related to 'safeguarding the partnership' phase of person-centred
      care'. Additionally a further theme 'barriers to person-centred care' was
      identified. CONCLUSION: We found evidence of all three person-centred care
      routines. Barriers to person-centred care comprised of lack team collaboration
      and resources. Facilitating patients to actively participate in decision-making
      during the weaning process may optimise weaning outcomes and warrants further
      research.

PMID- 29567411
TI  - Abnormal nuclear morphology is independent of longevity in a zmpste24-deficient
      fish model of Hutchinson-Gilford progeria syndrome (HGPS).
AB  - Lamin is an intermediate protein underlying the nuclear envelope and it plays a
      key role in maintaining the integrity of the nucleus. A defect in the processing
      of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of
      farnesylated prelamin in the nucleus and causes various diseases, including
      Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin
      processing is unclear in fish species. Here, we generated zmpste24-deficient
      medaka and evaluated their phenotype. Unlike humans and mice, homozygous mutants
      did not show growth defects or lifespan shortening, despite lamin precursor
      accumulation. Gonadosomatic indices, blood glucose levels, and regenerative
      capacity of fins were similar in 1-year-old mutants and their wild-type (WT)
      siblings. Histological examination showed that the muscles, subcutaneous fat
      tissues, and gonads were normal in the mutants at the age of 1 year. However, the
      mutants showed hypersensitivity to X-ray irradiation, although p53target genes,
      p21 and mdm2, were induced 6 h after irradiation. Immunostaining of primary
      cultured cells from caudal fins and visualization of nuclei using H2B-GFP fusion
      proteins revealed an abnormal nuclear shape in the mutants both in vitro and in
      vivo. The telomere lengths were significantly shorter in the mutants compared to
      WT. Taken together, these results suggest that zmpste24-deficient medaka
      phenocopied HGPS only partially and that abnormal nuclear morphology and lifespan
      shortening are two independent events in vertebrates.

PMID- 29567412
TI  - Lipidome-wide disturbances of human placental JEG-3 cells by the presence of
      MEHP.
AB  - During pregnancy, exposure to environmental contaminants can lead to adverse
      effects on fetal growth and development, especially by targeting the placenta.
      Di(2-ethylhexyl)phthalate (DEHP), the most abundant chemical used in plastic
      materials, is known to induce toxicity on animals reproductive system and is
      suspected to give rise to similar effect in humans. Toxicity of DEHP is due to
      its main metabolite, MEHP, which is also known to disturb lipid synthesis in
      several organs. Moreover, mono-(2-ethylhexyl)phtalate (MEHP) is a high affinity
      ligand of the peroxisome proliferator-activated receptor PPARgamma which is
      essential for placental development and lipid metabolism. In order to investigate
      possible lipid disruptions induced by MEHP, in the JEG-3 human trophoblast cell
      line, a differential lipidomic analysis was carried out by UPLC-MS on both
      exposed and control cells. Our results showed that MEHP induced an important
      change of JEG-3 cells lipidome, especially in glycerolipids and
      glycerophospholipids, with a marked accumulation of triacylglycerols. For the
      first time, our results highlighted adverse effects of MEHP on human placental
      cells lipidome and thus, its potential effect on placental physiology.

PMID- 29567413
TI  - Hepatocellular carcinoma risk assessment by the measurement of liver stiffness
      variations in HCV cirrhotics treated with direct acting antivirals.
AB  - BACKGROUND: Direct-acting antivirals (DAA) are an effective treatment for
      hepatitis C virus infection. However, sustained virologic response (SVR) after
      DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC)
      development in these patients. Liver stiffness measurement (LSM) may predict the
      risk of developing HCC in liver cirrhosis patients. AIMS: The aim of our study
      was to evaluate the role of LSM variation as predictor of HCC development in
      patients treated with DAA. METHODS: In 139 HCV-related cirrhotic patients, LSM
      and laboratory tests were carried out at baseline (BL) and at the end of DAA
      treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM
      reduction was expressed as Delta LS (?LS). Cox regression analysis was used to
      identify prognostic factors for HCC development after DAA. RESULTS: Median LSM
      values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p <
      0.001). The median ?LS was -26.7% (IQR: -38.4% -13.6%). During a median follow-up
      of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant
      LSM reduction was observed both in patients who developed HCC and in those who
      did not, but this was significantly lower in the patients who developed HCC (
      18.0% vs -28.9% p = 0.005). At multivariate analysis, ?LS lower than -30%, Child
      Turcotte-Pugh-B and history of HCC were independently associated with HCC
      development. CONCLUSION: Our results indicate that ?LS is a useful non-invasive
      marker for predicting HCC development after DAA treatment.

PMID- 29567414
TI  - Actinobacteria: A relevant minority for the maintenance of gut homeostasis.
AB  - Actinobacteria are one the four major phyla of the gut microbiota and, although
      they represent only a small percentage, are pivotal in the maintenance of gut
      homeostasis. During the last decade many studies focused the attention on
      Actinobacteria, especially on their role both in gastrointestinal and systemic
      diseases and on their possible therapeutic use. In fact, classes of this phylum,
      especially Bifidobacteria, are widely used as probiotic demonstrating beneficial
      effects in many pathological conditions, even if larger in vivo studies are
      needed to confirm such encouraging results. This review aims to explore the
      current knowledge on their physiological functions and to speculate on their
      possible therapeutic role(s) in gastrointestinal and systemic diseases.

PMID- 29567415
TI  - Clinical and prognostic implications of acute onset of Autoimmune Hepatitis: An
      Italian multicentre study.
AB  - Autoimmune Hepatitis (AIH) can present under clinical profile as acute hepatitis
      of unexplained cause. We analyzed clinical, therapeutical and prognostic
      implications of AIH presenting as acute hepatitis in a cohort of patients
      admitted to 3 referral Centres in Italy. AIH onset was considered acute when
      transaminases were higher than 10 times the normal limit and/or bilirubin higher
      than 5 mg/ml (irrespectively from the histology, available only in 62% of cases).
      Among 479 patients diagnosed as AIH, 202 (43%) met the criteria of acute onset.
      This former group of patients on the basis of the histology has been subdivided
      in the "genuine" acute onset (83 pts) and acute "on chronic" onset (45 pts) At
      onset, clinical acute AIH showed significantly higher ALT, bilirubin and INR
      levels (p < 0.001 for all), lower albumin values (p = 0.001), similar IgG levels;
      Response to treatment was similar between the two groups. The progression to
      liver cirrhosis or its complications was significantly less frequent in acute
      onset AIH (13% vs. 22%, p = 0.02). The "genuine" acute patients showed a higher
      albumin serum levels (40 vs. 36, p = 0.001), lower INR levels (1.12 vs. 1.26, p =
      0.002) and less tendency to the progression of liver disease (7% vs. 12%, p = NS)
      with respect to acute "on chronic" onset patients. Clinical acute hepatitis
      represents a common presentation of AIH, responds to standard immunosuppression
      regimen and would seem to be correlated with a better long-term prognosis.

PMID- 29567417
TI  - Toward transforming neuropsychology into the "hard" science: Comments on "Physics
      of mind: Experimental confirmations of theoretical predictions" by Felix
      Schoeller, Leonid Perlovsky, Dmitry Arseniev.

PMID- 29567416
TI  - Responses of seminal wheat seedling roots to soil water deficits.
AB  - The aims of this paper are to develop our understanding of the ways by which soil
      water deficits influence early wheat root growth responses, particularly how
      seminal roots respond to soil drying and the extent to which information on
      differences in soil water content are conveyed to the shoot and their impact on
      shoot behaviour. To achieve this, wheat seedlings have been grown, individually
      for around 25 days after germination in segmented soil columns within vertical
      plastic compartments. Roots were exposed to different soil volumetric moisture
      contents (SVMC) within the two compartments. Experiments where the soil in the
      lower compartment was allowed to dry to different extents, while the upper was
      maintained close to field capacity, showed that wheat seedlings allocated
      proportionally more root dry matter to the lower drier soil compartment. The
      total production of root, irrespective of the upper or lower SVMC, was similar
      and there were no detected effects on leaf growth rate or gas exchange. The
      response of seminal roots to proportionally increase their allocation of dry
      matter, to the drier soil was unexpected with such plasticity of roots system
      development traditionally linked to heterogeneous nutrient distribution than
      accessing soil water. In experiments where the upper soil compartment was allowed
      to dry, root growth slowed and leaf growth and gas exchange declined. Subsequent
      experiments used root growth rates to determine when seminal root tips first came
      into contact with drying soil, with the intentions of determining how the
      observed root growth rates were maintained as an explanation for the observed
      changes in root allocation. Measurements of seminal root ABA and ethylene from
      roots within the drying soil are interpreted with respect to what is known about
      the physiological control of root growth in drying soil.

PMID- 29567418
TI  - Plasticizer, di(2-ethylhexyl)phthalate (DEHP) enhances cockroach allergen extract
      driven airway inflammation by enhancing pulmonary Th2 as well as Th17 immune
      responses in mice.
AB  - In recent decades, there has been a gradual increase in the prevalence of asthma.
      Various factors including environmental pollutants have contributed to this
      phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest
      environmental pollutants due to its association with plastic products. DEHP gets
      released from plastic products easily leading to respiratory exposure in humans.
      As a consequence, DEHP is associated with allergic asthma in humans and animals.
      DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of
      asthma at high doses. However, these studies mostly looked into the role of DEHP
      on Th2 cytokines/eosinophilic inflammation without investigating the role of
      airway epithelial cells (AECs)/dendritic cells (DCs)/Th17 cells. Its adjuvant
      activity with natural allergens such as cockroach allergens at tolerable daily
      intake needs to be explored. Cockroach allergens and DEHP may be inhaled together
      due to their coexistence in work place as well as household environments.
      Therefore, effect of DEHP was assessed in cockroach allergens extract (CE)
      induced mouse model of asthma. Airway inflammation, histopathology, mucus
      secretion, and immune responses related to Th2/Th17/DCs and AECs were assessed in
      mice with DEHP exposure alone and in combination with CE. Our study shows that
      DEHP converts CE-induced eosinophilic inflammation into mixed granulocytic
      inflammation by promoting Th2 as well as Th17 immune responses. This was probably
      due to downregulation of E-cadherin in AECs, and enhancement of costimulatory
      molecules (MHCII/CD86/CD40)/pro-inflammatory cytokines (IL-6/MCP-1) in DCs by
      DEHP. This suggests that DEHP facilitates development of mixed granulocytic
      airway inflammation in the presence of a natural allergen.

PMID- 29567419
TI  - Validity of self-reported indicators to assess secondhand smoke exposure in the
      home.
AB  - INTRODUCTION: Questionnaires are widely used to assess secondhand smoke (SHS)
      exposure. However, the validity of self-reported SHS exposure indicators has been
      rarely assessed. We aimed to assess correlations, sensitivity, specificity, and
      predictive values between self-reported SHS exposure indicators and airborne
      nicotine concentrations. METHODS: We performed a cross-sectional study with a
      convenience sample of 175 homes in Barcelona and Santiago de Compostela, Spain.
      Airborne nicotine samples were collected from participants' homes and a self
      administered questionnaire was completed on SHS exposure in the home. Spearman
      correlations coefficients and sensitivity, specificity and predictive values were
      assessed between self-reported SHS exposure indicators and nicotine
      concentrations in the home. RESULTS: All self-reported SHS exposure indicators
      correlated moderately strongly with airborne nicotine concentrations (Spearman
      correlations coefficient ranging from 0.58 to 0.65). Moreover, sensitivities and
      negative predictive values between self-reported indicators and the presence of
      nicotine in the home were below 66.4% while specificities and positive predictive
      values were over 78.4%. The "number of people usually smoking in the home" showed
      the best results (rs = 0.65, p < 0.001; sensitivity = 50.4%, specificity = 95.2%,
      PPV = 95.0, NPV = 51.3). CONCLUSIONS: The self-reported SHS indicators assessed
      in this study showed moderate and strong correlations, low sensitivities, and
      high specificities. Among them, the best results were obtained with the "number
      of people usually smoking in the home".

PMID- 29567420
TI  - A study of telomere length, arsenic exposure, and arsenic toxicity in a
      Bangladeshi cohort.
AB  - BACKGROUND: Chronic arsenic exposure is associated with increased risk for
      arsenical skin lesions, cancer, and other adverse health outcomes. One potential
      mechanism of arsenic toxicity is telomere dysfunction. However, prior
      epidemiological studies of arsenic exposure, telomere length (TL), and skin
      lesion are small and cross-sectional. We investigated the associations between
      arsenic exposure and TL and between baseline TL and incident skin lesion risk
      among individuals participating in the Health Effects of Arsenic Longitudinal
      Study in Bangladesh (2000-2009). METHODS: Quantitative PCR was used to measure
      the average TL of peripheral blood DNA collected at baseline. The association
      between baseline arsenic exposure (well water and urine) and TL was estimated in
      a randomly-selected subcohort (n = 1469). A nested case-control study (466 cases
      and 464 age- and sex-matched controls) was used to estimate the association
      between baseline TL and incident skin lesion risk (diagnosed < 8 years after
      baseline). RESULTS: No association was observed between arsenic exposure (water
      or urine) and TL. Among incident skin lesion cases and matched controls, we
      observed higher skin lesion risk among individuals with shorter TL (Ptrend = 1.5
      * 10-5) with odds ratios of 2.60, 1.59, and 1.10 for the first (shortest),
      second, and third TL quartiles compared to the fourth (longest). CONCLUSIONS:
      Arsenic exposure was not associated with TL among Bangladeshi adults, suggesting
      that leukocyte TL may not reflect a primary mode of action for arsenic's
      toxicity. However, short TL was associated with increased skin lesion risk, and
      may be a biomarker of arsenic susceptibility modifying arsenic's effect on skin
      lesion risk.

PMID- 29567421
TI  - Phytoremediation of sewage sludge contaminated by trace elements and organic
      compounds.
AB  - Phytoremediation is a green technique being increasingly used worldwide for
      various purposes including the treatment of municipal sewage sludge (MSS). Most
      plants proposed for this technique have high nutrient demands, and fertilization
      is often required to maintain soil fertility and nutrient balance while
      remediating the substrate. In this context, MSS could be a valuable source of
      nutrients (especially N and P) and water for plant growth. The aim of this study
      was to determine the capacity willow (Salix matsudana, cv Levante), poplar
      (Populus deltoides * Populus nigra, cv Orion), eucalyptus (Eucalyptus
      camaldulensis) and sunflower (Helianthus annuus) to clean MSS, which is slightly
      contaminated by trace elements (TEs) and organic pollutants, and to assess their
      physiological response to this medium. In particular, we aimed to evaluate the TE
      accumulation by different species as well as the decrease of TEs and organic
      pollutants in the sludge after one cropping cycle and the effect of MSS on plant
      growth and physiology. Since MSS did not show any detrimental effect on the
      biomass yield of any of the species tested, it was found to be a suitable growing
      medium for these species. TE phytoextraction rates depended on the species, with
      eucalyptus showing the highest accumulation for Cr, whereas sunflower exhibited
      the best performance for As, Cu and Zn. At the end of the trial, some TEs (i.e.
      Cr, Pb and Zn), n-alkanes and PCBs showed a significant concentration decrease in
      the sludge for all tested species. The highest Cr decrease was observed in pots
      with eucalyptus (57.4%) and sunflower (53.4%), whereas sunflower showed the
      highest Cu decrease (44.2%), followed by eucalyptus (41.2%), poplar (16.2%) and
      willow (14%). A significant decrease (41.1%) of Pb in the eucalyptus was
      observed. Zn showed a high decrease rate with sunflower (59.5%) and poplar (52%)
      and to a lesser degree with willow (35.3%) and eucalyptus (25.4%). The highest
      decrease in n-alkanes concentration in the sludge was found in willow (98.3%) and
      sunflower (97.3%), whereas eucalyptus has the lowest PCBs concentration (91.8%)
      in the sludge compared to the beginning of the trial. These results suggest new
      strategies (e.g. crop rotation and intercropping) to be adopted for a better
      management of this phytotechnology.

PMID- 29567422
TI  - Neuroprotective effect of IDPU (1-(7-imino-3-propyl-2,3-dihydrothiazolo [4,5
      d]pyrimidin-6(7H)-yl)urea) in 6-OHDA induced rodent model of hemiparkinson's
      disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative motor disorder
      characterized by the degeneration of dopaminergic nigrostriatal neurons. Levodopa
      (l-DOPA) is the most effective therapy for PD, however, PD progression continues
      with significant side effects in long term, thus necessitating the search for
      effective therapy that impedes PD progression. PD therapy through non
      dopaminergic pathways offers treatment without the risk of extrapyramidal
      effects. In this regard, earlier, we had reported, a novel compound IDPU with
      potential adenosine A2A receptor antagonist effect in haloperidol (chronic
      treatment) induced Parkinson model. In the present study, we extended our
      investigation towards i) evaluation of IDPU in well-established 6-OHDA induced
      Parkinson rat model to establish its role in the therapy of PD ii) its function
      in alleviating the neuronal loss. We carried the IDPU administration (i.p.) in
      rats for two weeks after establishing 6-OHDA induced unilateral lesions. The
      behavioral activity, neurochemical alteration, oxidative stress marker and
      tyrosine hydroxylase positive neurons in substantia nigra were analyzed. The
      results showed that IDPU significantly reduced motor and non-motor deficits
      induced by 6-OHDA in the behavioral tasks such as apomorphine, rota rod and force
      swim test. Furthermore, the results of oxidative stress biomarkers revealed that
      IDPU successfully modulated oxidative stress associated biomarkers such as MDA,
      catalase, superoxide dismutase, nitric oxide and reduced glutathione level.
      Additionally, IDPU significantly elevated intracellular dopamine, decreased
      glutamate and calcium levels in brain as compared to 6-OHDA alone treated animals
      which is evocative of its neuroprotective behavior. Thus, the investigations
      clearly validated IDPU as a potent anti-parkinsonian agent which showed immense
      capability to protect neurodegeneration.

PMID- 29567423
TI  - Alzheimer disease associated variants in SORL1 accelerate dementia development in
      Parkinson disease.
AB  - OBJECTIVE: Dementia in Parkinson disease (PD) is a common occurrence, and shows a
      marked overlap at a clinical and pathological level with Alzheimer's disease
      (AD), suggesting they share underlying disease mechanisms. Genetic variants in
      SORL1 have been identified in patients with AD, but a possible role in other
      dementias is unknown. The aim of this study was to investigate whether common
      polymorphisms in SORL1 affect the risk of developing dementia in a population
      based cohort of patients with incident PD. METHODS: One common, nonsynonymous
      SORL1 variant (rs2298813; A528T) was identified in whole exome sequencing data
      from 185 patients with PD from the Norwegian ParkWest study, who had been
      followed up to the 7-year visit after diagnosis. A528T was tested for association
      with PD risk, the development of dementia, and in a subset of patients (n = 103)
      for associations with established AD cerebrospinal fluid (CSF) biomarkers
      measured at the time of PD diagnosis. RESULTS: We found an association of A528T
      carrier status with increased risk of developing PD dementia (HR 2.31; 95% CI
      1.09-4.90; p = 0.03) compared to non-carriers. Additionally, A528T carrier status
      was associated with a reduced ratio of CSF beta-amyloid 42 to p-Tau (p = 0.014)
      but no alterations in absolute AD marker levels (all p > 0.05) at the time of PD
      diagnosis. CONCLUSION: Our results show the first association of the AD risk
      factor SORL1 with incident dementia in PD, providing new evidence that AD related
      disease mechanisms may contribute to dementia in a subset of patients with PD.
      Finding support for a shared etiology for AD and PD dementia provides new
      directions for research into treatments for these diseases.

PMID- 29567424
TI  - Altered intrinsic brain functional connectivity in drug-naive Parkinson's disease
      patients with LRRK2 mutations.
AB  - BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) has been recently identified as
      a causative gene of Parkinson's disease (PD), and the LRRK2 R1628P and G2385R
      mutations are common in ethnic Han-Chinese PD patients. However, the pathogenic
      mechanism of LRRK2 mutations in PD remains largely unknown. METHODS: Resting
      state functional MRI (fMRI) was used to assess the functional connectivity (FC)
      of the striatal subregions of 11 ethnic Han-Chinese drug-naive PD patients with
      the LRRK2 R1628P or G2385R mutations, 11 ethnic Han-Chinese drug-naive PD
      patients without such mutations, and 22 healthy control (HC) subjects. RESULTS:
      Compared with the HC subjects, both subgroups of the PD patients showed
      alterations in the FC within the sensorimotor-striatal and posterior putamen
      striatal circuits. In addition, relative to the subgroup of PD patients without
      the LRRK2 mutations, the subgroup of PD patients with the LRRK2 mutation
      exhibited decreased FC between the putamen and the bilateral superior frontal
      gyri, precuneus and calcarine gyri. The FC between the putamen and the bilateral
      superior frontal gyri decreased with age in the LRRK2 mutation carriers but not
      in the non-carriers. CONCLUSION: Differences in the FC between ethnic Han-Chinese
      drug-naive PD patients with and without the LRRK2 mutation may provide new
      insights into the understanding of the neural functional changes in ethnic Han
      Chinese PD patients with LRRK2 mutations. However, our results are preliminary,
      and further investigations are needed.

PMID- 29567425
TI  - Association between self-reported impulsiveness and gray matter volume in healthy
      adults. An exploratory MRI study.
AB  - This exploratory study investigated the association between self-reported
      impulsiveness and cortical gray matter volume (GMV) of the entire cortex in
      healthy adults. As a secondary objective and based on preliminary findings
      concerning the positive association between self-reported impulsiveness and the
      slant of the forehead degrees (SFD), we analyzed associations between SFD, GMV
      and impulsiveness. We obtained 48 structural magnetic resonances. The
      participants also completed BIS 11 and profile pictures were obtained. SFD was
      measured by a photographic support and a protractor. The GMV of the whole cortex
      was obtained for each participant through Freesurfer. Firstly, we found negative
      and positive correlations between fronto-temporal and occipital areas
      respectively and BIS. Second, we found negative correlations between SFD and GMV
      in right postcentral gyrus, right caudal middle frontal gyrus, right transverse
      temporal cortex and positive correlation in left entorhinal cortex. Third, we
      observed a positive correlation between SFD and BIS in all impulsiveness scores.
      In conclusion, variations in fronto-temporal and posterior cerebral areas are
      crucial for BIS in healthy adults. Furthermore, SFD was associated with BIS and
      correlated with GMV areas involved in self-reported impulsiveness.

PMID- 29567426
TI  - miR-494-3p modulates the progression of in vitro and in vivo Parkinson's disease
      models by targeting SIRT3.
AB  - Parkinson's disease (PD) is the second most prevalent chronic and progressive
      neurodegenerative disease. Plenty of miRNAs have been demonstrated to participate
      in the pathogenesis of PD. However, the detailed roles of miR-494-3p and
      underlying mechanisms involved in PD progression remain to be explored. In the
      present study, we found that miR-494-3p expression was increased and sirtuin 3
      (SIRT3) expression was decreased in SH-SY5Y cells following 1-Methyl-4
      phenylpyridinium (MPP+) treatment. Loss-of-function showed that miR-494-3p
      inhibition promoted cell viability and superoxide dismutase (SOD) activity, and
      suppressed apoptotic rate, caspase-3 activity, lactate dehydrogenase (LDH)
      activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) expressions, and reactive oxygen species (ROS) generation in MPP+-induced
      SH-SY5Y cells. Moreover, SIRT3 was identified as a target of miR-494-3p and miR
      494-3p negatively regulated SIRT3 expression in SH-SY5Y cells. Additionally, up
      regulation of miR-494-3p suppressed SIRT3 expression and exacerbated motor
      impairment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD
      mouse model. In conclusion, miR-494-3p inhibition exerted a neuroprotective role
      in MPP+-induced PD by targeting SIRT3, providing a possible therapeutic strategy
      for PD patients.

PMID- 29567427
TI  - N-acylethanolamine hydrolyzing acid amidase inhibition: tools and potential
      therapeutic opportunities.
AB  - N-acylethanolamines (NAEs) (e.g., N-palmitoylethanolamine, N
      arachidonoylethanolamine, N-oleoylethanolamine) are bioactive lipids involved in
      many physiological processes including pain, inflammation, anxiety, cognition and
      food intake. Two enzymes are responsible for the hydrolysis of NAEs and therefore
      regulate their endogenous levels and effects: fatty acid amide hydrolase (FAAH)
      and N-acylethanolamine-hydrolyzing acid amidase (NAAA). As discussed here,
      extensive biochemical characterization of NAAA was carried out over the years
      that contributed to a better understanding of NAAA enzymology. An increasing
      number of studies describe the synthesis and pharmacological characterization of
      NAAA inhibitors. Recent medicinal chemistry efforts have led to the development
      of potent and stable inhibitors that enable studying the effects of NAAA
      inhibition in preclinical disease models, notably in the context of pain and
      inflammation.

PMID- 29567428
TI  - Synthesis, molecular modelling and biological evaluation of tetrasubstituted
      thiazoles towards cholinesterase enzymes and cytotoxicity studies.
AB  - Alzheimer is a neurodegenerative disease and requires the development of new
      scaffold to treat it. In this regard, thiazoles derivative are playing their
      significant role. In the current research paper we have focused our attention for
      the development of tetrasubstituted thiazole (3a-h) derivatives using domino
      synthesis by mixing the thiourea as a precursor, with acetophenone in the
      presence of iodine and tosic acid in DMSO and refluxed for 12-22 h. The
      structures of the newly synthesized compounds were confirmed by FTIR, 1H NMR, 13C
      NMR and EIMS analysis. Thiazole derivatives were analyzed for their biological
      significances against acetyl and butylcholinesterase enzymes and compound 3b and
      3d were found more active against these enzyme, respectively. The mode of
      inhibition was determined for the potent compounds against both the enzymes.
      Moreover, the molecular docking studies were carried out to explore the
      interactive behavior of the compounds within the active pocket of enzymes.
      Furthermore, the derivatives (3a-h) were evaluated for their anticancer potential
      against HeLa cancer cell lines. Most potent inhibition was observed by compound
      3b.

PMID- 29567429
TI  - Design, synthesis and biological evaluation of novel 1,3,4-trisubstituted
      pyrazole derivatives as potential chemotherapeutic agents for hepatocellular
      carcinoma.
AB  - A series of novel 1,3,4-trisubstituted pyrazole derivatives were synthesized and
      evaluated for their cytotoxic activity against three different cancer cell lines
      namely HCT116, UO-31 and HepG2. Compounds 3b, 3d, 7b and 9 showed excellent
      anticancer activity against all the tested cancer cell lines and had better
      cytotoxic activities than the reference drug, Sorafenib. Therefore, these
      compounds were chosen to be further evaluated in a panel of HCC cell lines. Among
      them, 3b and 7b were the most active compounds against HCC cells used here.
      Further studies on the mechanism demonstrated that 3b and 7b induced apoptosis in
      addition to induction of cell cycle arrest at G2/M phase in HepG2 and Huh7 cells.
      Consistent with these results, caspase-3 assay was done and the results revealed
      that the pro-apoptotic activity of the target compounds could be due to the
      stimulation of caspases-3. In addition, CDK1 inhibition assay was done and it was
      found that compounds 3b and 7b inhibited CDK1 activities with IC50 values of 2.38
      and 1.52 uM, respectively. Finally, pyrazole derivatives 3b and 7b showed potent
      bioactivities, indicating that these compounds could be potent anticancer drugs
      in the future.

PMID- 29567430
TI  - IPEX due to an exon 7 skipping FOXP3 mutation with autoimmune diabetes mellitus
      cured by selective TReg cell engraftment.
AB  - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
      is a rare inherited disorder leading to severe organ-specific autoimmunity. IPEX
      is caused by hemizygous mutations in FOXP3, which codes for a master
      transcription factor of regulatory T (TReg) cell development and function. We
      describe a four-year-old boy with typical but slightly delayed-onset of IPEX with
      autoimmune diabetes mellitus, enteropathy, hepatitis and skin disease. We found
      the unreported FOXP3 splice site mutation c.816+2T>A that leads to the loss of
      leucine-zipper coding exon 7. RNA-Seq revealed that FOXP3Delta7 leads to
      differential expression of FOXP3 regulated genes. After myeloablative
      conditioning the patient underwent allogeneic HSCT from a matched unrelated
      donor. HSCT led to the resolution of all IPEX symptoms including insulin
      requirement despite persisting autoantibody levels. After initial full donor
      engraftment nearly complete autologous reconstitution was documented, but donor
      derived TReg cells persisted with a lineage-specific chimerism of >70% and the
      patient remained in clinical remission.

PMID- 29567431
TI  - Immunomodulating peptides derived from different human endogenous retroviruses
      (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal
      disease model.
AB  - Retroviruses including Human Endogenous Retroviruses (HERVs), contain a conserved
      region with highly immunomodulatory functions in the transmembrane proteins in
      envelope gene (env) named immunosuppressive domain (ISU). In this report, we
      demonstrate that Env59-GP3 peptide holds therapeutic potential in a mouse model
      of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE). The results show that this specific HERV-H derived ISU
      peptide, but not peptide derived from another env gene HERV-K, decreased the
      development of EAE in C57BL/6 mice, accompanied by reduced demyelination and
      inhibition of inflammatory cells. Moreover, here we tested the effect of peptides
      on macrophages differentiation. The treatment with Env59-GPS peptide modulate the
      pro-inflammatory M1 profile and anti-inflammatory M2 macrophages, being shown by
      inhibiting inflammatory M1 hallmark genes/cytokines expression and enhancing
      expression of M2 associated markers. These results demonstrate that Env59-GP3 ISU
      peptide has therapeutic potential in EAE possibly through inducing the
      polarization of M2 macrophages and inhibiting inflammatory responses.

PMID- 29567432
TI  - Exploiting risk-reward structures in decision making under uncertainty.
AB  - People often have to make decisions under uncertainty-that is, in situations
      where the probabilities of obtaining a payoff are unknown or at least difficult
      to ascertain. One solution to this problem is to infer the probability from the
      magnitude of the potential payoff and thus exploit the inverse relationship
      between payoffs and probabilities that occurs in many domains in the environment.
      Here, we investigated how the mind may implement such a solution: (1) Do people
      learn about risk-reward relationships from the environment-and if so, how? (2)
      How do learned risk-reward relationships impact preferences in decision-making
      under uncertainty? Across three experiments (N = 352), we found that participants
      can learn risk-reward relationships from being exposed to choice environments
      with a negative, positive, or uncorrelated risk-reward relationship. They were
      able to learn the associations both from gambles with explicitly stated payoffs
      and probabilities (Experiments 1 & 2) and from gambles about epistemic events
      (Experiment 3). In subsequent decisions under uncertainty, participants often
      exploited the learned association by inferring probabilities from the magnitudes
      of the payoffs. This inference systematically influenced their preferences under
      uncertainty: Participants who had been exposed to a negative risk-reward
      relationship tended to prefer the uncertain option over a smaller sure option for
      low payoffs, but not for high payoffs. This pattern reversed in the positive
      condition and disappeared in the uncorrelated condition. This adaptive change in
      preferences is consistent with the use of the risk-reward heuristic.

PMID- 29567433
TI  - Phage particles harboring antibiotic resistance genes in fresh-cut vegetables and
      agricultural soil.
AB  - Bacteriophages are ubiquitously distributed prokaryotic viruses that are more
      abundant than bacteria. As a consequence of their life cycle, phages can kidnap
      part of their host's genetic material, including antibiotic resistance genes
      (ARGs), which released phage particles transfer in a process called transduction.
      The spread of ARGs among pathogenic bacteria currently constitutes a serious
      global health problem. In this study, fresh vegetables (lettuce, spinach and
      cucumber), and cropland soil were screened by qPCR for ten ARGs (blaTEM, blaCTX-M
      1 group, blaCTX-M-9 group, blaOXA-48, blaVIM, mecA, sul1, qnrA, qnrS and armA) in
      their viral DNA fraction. The presence of ARGs in the phage DNA was analyzed
      before and after propagation experiments in an Escherichia coli host strain to
      evaluate the ability of the phage particles to infect a host. ARGs were found in
      the phage DNA fraction of all matrices, although with heterogeneous values. ARG
      prevalence was significantly higher in lettuce and soil, and the most common
      overall were beta-lactamases. After propagation experiments, an increase in ARG
      densities in phage particles was observed in samples of all four matrices,
      confirming that part of the isolated phage particles were infectious. This study
      reveals the abundance of free, replicative ARG-containing phage particles in
      vegetable matrices and cropland soil. The particles are proposed as vehicles for
      resistance transfer in these environments, where they can persist for a long
      time, with the possibility of generating new resistant bacterial strains.
      Ingestion of these mobile genetic elements may also favor the emergence of new
      resistances, a risk not previously considered.

PMID- 29567435
TI  - Piezotome Genioplasty Reduces Postsurgical Morbidity and Enhances Patient
      Satisfaction: A Randomized Clinical Trial.
AB  - PURPOSE: Recent clinical studies have shown piezotomes might establish the new
      "state of the art" for osteotomies in maxillofacial surgery. The author
      hypothesized genioplasty surgery with piezotomes might decrease postsurgical
      morbidity and increase overall patient satisfaction compared with genioplasty
      with traditional instruments. MATERIALS AND METHODS: The author implemented a
      randomized clinical trial. The sample was composed of patients undergoing
      reductive genioplasty. The predictor variable was genioplasty performed with
      traditional instruments and a traditional sliding genioplasty protocol (control
      group) or ultrasonic surgical devices (Piezotome II and Piezotome SOLO M+) with a
      piezotome-adapted 3-dimensional curved osteotomy surgical protocol (test group).
      The primary outcome variable was overall long-term patient satisfaction
      determined by the Genioplasty Outcome Evaluation. Other study variables were
      postsurgical morbidity assessed by the Universal Pain Assessment Scale, analgesic
      intake, neurosensory 2-point discrimination test of the lip and chin, and surgery
      duration. Descriptive and bivariate statistics were computed by SPSS 22.0 and the
      P value was set at .05. RESULTS: The sample was composed of 48 patients
      undergoing reductive genioplasty with a piezotome (10 men and 13 women; age, 24
      to 56 yr) or traditional sliding genioplasty (11 men and 14 women; age, 26 to 54
      yr). No statistically relevant difference was found for surgery duration between
      the test and control groups. There was a statistically significant association
      between decreased postsurgical morbidity (P < .05) and higher overall long-term
      patient satisfaction with genioplasty outcome (P < .05) when piezotomes were used
      for performing the genioplasty. CONCLUSION: The results of this study suggest the
      use of piezotomes and piezotome-adapted surgical protocols is advantageous in
      genioplasty surgery compared with traditional surgical instruments and
      traditional surgical protocols.

PMID- 29567434
TI  - Using a local low rank plus sparse reconstruction to accelerate dynamic
      hyperpolarized 13C imaging using the bSSFP sequence.
AB  - Acceleration of dynamic 2D (T2 Mapping) and 3D hyperpolarized 13C MRI
      acquisitions using the balanced steady-state free precession sequence was
      achieved with a specialized reconstruction method, based on the combination of
      low rank plus sparse and local low rank reconstructions. Methods were validated
      using both retrospectively and prospectively undersampled in vivo data from
      normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D
      dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of
      0.25-1 mm2 2D dynamic acquisitions was achieved. This enabled visualization of
      the biodistribution of [2-13C]pyruvate, [1-13C]lactate, [13C, 15N2]urea, and
      HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of
      high resolution T2 maps.

PMID- 29567436
TI  - The Effects of Noncontinuous Positive Airway Pressure Therapies on the
      Aerodynamic Characteristics of the Upper Airway of Obstructive Sleep Apnea
      Patients: A Systematic Review.
AB  - PURPOSE: The effects of noncontinuous positive airway pressure (non-CPAP)
      therapies on the airflow in the upper airway in obstructive sleep apnea (OSA)
      patients are not completely clear yet. Therefore, the primary aim of this
      systematic review was to determine the effects of various non-CPAP therapies on
      the aerodynamic characteristics of the upper airway in OSA patients. MATERIALS
      AND METHODS: A PICO (population or patient, intervention, comparison, outcome)
      search strategy, focusing on the effects of various non-CPAP therapies on the
      aerodynamic characteristics of the upper airway (ie, velocity, wall shear stress,
      wall static pressure, airway resistance, pressure drop, and pressure effort) of
      OSA patients, was conducted in the following databases: MEDLINE (PubMed), Embase
      (Excerpta Medica), and Web of Science. In this systematic review, the inclusion
      criteria were 1) adults diagnosed with OSA by polysomnography, 2) treatment
      outcome assessed by a second polysomnography, and 3) computational fluid dynamics
      (CFD) applied. RESULTS: Of 51 unique studies retrieved, 9 fulfilled the criteria
      for this systematic review. Seven studies were on maxillomandibular advancement
      (MMA) surgery, and 2 were on mandibular advancement device (MAD) therapy. The
      aerodynamic characteristics of the upper airway improved in OSA patients who
      underwent MMA surgery. However, the studies on MMA surgery included only
      responders to MMA surgery. In the responders to MAD therapy, the velocity, wall
      static pressure, and airway resistance of the upper airway decreased. In
      nonresponders to MAD therapy, the wall static pressure and airway resistance of
      the upper airway increased. CONCLUSIONS: This systematic review suggests that MMA
      surgery and MAD therapy may improve several aerodynamic characteristics of the
      upper airway in OSA patients by CFD analysis. However, because of limitations of
      the selected studies, there is not enough evidence yet to support CFD analysis as
      a routine tool to predict the treatment outcome in OSA patients.

PMID- 29567437
TI  - Time to Reconsider Management of the Temporomandibular Joint in Juvenile
      Idiopathic Arthritis.
AB  - The temporomandibular joints are often affected by juvenile idiopathic arthritis,
      but few evidence-based management strategies exist. Intra-articular steroid
      injection (IASI) is a common intervention and is associated with pain reduction
      and improved mandibular function. Emerging evidence, however, suggests that IASI
      may actually impair rather than improve mandibular growth. It is therefore time
      to reconsider this practice.

PMID- 29567438
TI  - Intentional tanning among adolescents in seven Canadian provinces: Provincial
      comparisons (CRAYS 2015).
AB  - This report explores intentional tanning behaviors among Canadian high school
      students in light of provincial restrictions on UV tanning device use among
      youth. Data are from the Cancer Risk Assessment in Youth Survey (CRAYS),
      collected from January to December 2015, at randomly selected high schools in 7
      provinces. Relevant variables were: tanning methods ever used, demographics, and
      location and refusal of UV tanning device (beds, lamps) use in the past 12
      months. Data were weighted so total survey weights by male/female, grade and
      province equal actual enrolments in these groups. Analyses were conducted in SAS,
      mostly for grades 10 and 11. Rao-Scott chi squared tests and p-values were
      calculated. Among 6803 grade 10 and 11 participants, 82% tanned intentionally,
      mostly by being/playing outside, or laying in the sun. Spray/self-tanners were
      used by 15% of participants. UV tanning device use was uncommon (4.4%), lowest in
      Ontario (2.7%) and British Columbia (3.8%), which have legislation against use
      among youth. Of 202 who used UV tanning devices in the past 12 months, most did
      at salons/studios (85%), 35% at home and 30% at a gym. Two hundred and forty-nine
      participants (3.4%) were refused use of UV tanning devices in the past 12 months.
      While legislation appears to deter UV tanning device use, it appears to have no
      impact on UV exposure among high school students overall. Greater prevention
      efforts are required to deter intentional tanning among high school students.

PMID- 29567439
TI  - Preventive care utilization: Association with individual- and workgroup-level
      policy and practice perceptions.
AB  - Preventive medical care may reduce downstream medical costs and reduce population
      burden of disease. However, although social, demographic, and geographic
      determinants of preventive care have been studied, there is little information
      about how the workplace affects preventive care utilization. This study examines
      how four types of organizational policies and practices (OPPs) are associated
      with individual workers' preventive care utilization. We used data collected in
      2012 from 838 hospital patient care workers, grouped in 84 patient care units at
      two hospitals in Boston. Via survey, we assessed individuals' perceptions of four
      types of OPPs on their work units. We linked the survey data to a database
      containing detailed information on medical expenditures. Using multilevel models,
      we tested whether individual-level perceptions, workgroup-average perceptions,
      and their combination were associated with individual workers' preventive care
      utilization (measured by number of preventive care encounters over a two-year
      period). Adjusting for worker characteristics, higher individual-level
      perceptions of workplace flexibility were associated with greater preventive care
      utilization. Higher average unit-level perceptions of people-oriented culture,
      ergonomic practices, and flexibility were associated with greater preventive care
      utilization. Overall, we find that workplace policies and practices supporting
      flexibility, ergonomics, and people-oriented culture are associated with positive
      preventive care-seeking behavior among workers, with some policies and practices
      operating at the individual level and some at the group level. Improving the work
      environment could impact employers' health-related expenditures and improve
      workers' health-related quality of life.

PMID- 29567440
TI  - A Modified Atrial Volume Reduction Technique for a Giant Left Atrium.
AB  - We describe a modified volume reduction technique for a giant left atrium that
      consists of circumferential resection of a strip of left atrial wall with the
      appendage, plicated pericardium replacing the posterior atrial wall, and
      anastomoses of the remaining right side free wall to the interatrial septum
      instead of the interatrial groove. Our initial application showed that this
      technique can safely reduce a giant left atrium to the desired volume and obtain
      a high rate of sinus rhythm restoration after a maze operation.

PMID- 29567441
TI  - Harlequin Effect in Angiography on Extracorporeal Membrane Oxygenation Mimicking
      Aortic Dissection.

PMID- 29567442
TI  - Spontaneous Right Atrial Dissection and Congenital Right Atrial Aneurysm.
AB  - Right atrial (RA) wall dissection and congenital RA aneurysm is a very rare
      abnormality. This is may be the first reported case of a spontaneous dissection
      of the RA wall without rupture, in addition to the presence of a congenital RA
      aneurysm. The patient, a 4-year-old boy, was successfully treated with RA
      aneurysm resection under cardiopulmonary bypass. Although the diagnosis of RA
      dissection poses a challenge even when the advanced multimodality imaging
      approaches are applied, transthoracic and contrast echocardiography are most
      valuable tools for making accurate diagnosis.

PMID- 29567443
TI  - Simultaneous determination of 21 trace perfluoroalkyl substances in fish by
      isotope dilution ultrahigh performance liquid chromatography tandem mass
      spectrometry.
AB  - Perfluoroalkyl substances (PFASs) have been identified as emerging environmental
      contaminants. In this study, an efficient and accurate ultrahigh performance
      liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed
      for simultaneous determination of 21 PFASs in fish. Acetonitrile was used for
      sample extraction. Solid phase extraction (SPE) by WAX cartridges and then
      freezing at -30  degrees C were adopted as cleanup strategies. Strict
      measurements were performed to control background contamination during the whole
      procedure. Matrix effects were evaluated by external standard and isotope
      dilution mass spectrometry (IDMS) methods. IDMS can compensate the matrix effects
      to a large extent. The method detection limits (MDLs) ranged from 2 pg/g to 10
      pg/g except for PFBA (120 pg/g). The method quantitation limits (MQLs) ranged
      from 5 pg/g to 30 pg/g except for PFBA (300 pg/g). The matrix spiked recoveries
      of three spiked levels were in the range of 79.6%-109%. The intra-day relative
      standard deviation (RSD) and inter-day RSD were from 0.94% to 13.9% and 0.36% to
      11.2% respectively. Two fish tissue reference materials were analyzed by the
      developed method. The results of reference materials were within the uncertainty
      of the given value. The quantitative results of IDMS and standard addition (SA) -
      IDMS were comparable. The developed UHPLC-MS/MS method was applied for PFASs
      detection in 20 marine fish samples. 9 PFASs were detected in the samples with
      the ?9PFASs concentration range of 0.04 to 2.14 ng/g wet weight (ww).

PMID- 29567444
TI  - Pollutant emissions from residential combustion and reduction strategies
      estimated via a village-based emission inventory in Beijing.
AB  - Accurate estimation of pollutant emissions from household solid fuel combustion
      has been a challenging issue in developing regions, especially in the heavily
      polluted northern China region. Basing on a survey of residential household
      energy use in all villages in Beijing, this study developed a village-based
      emission inventory of PM2.5, SO2, NOx, and NMVOCs emitted from household
      combustion in Beijing, as well as three emission control scenarios. Notably, 3805
      kt and 556 kt of coal were used for household heating and cooking in 2015,
      respectively. The emissions of NOX, NMVOCs, SO2, and PM2.5forhousehold heating
      totaled11.5 kt, 29.3 kt, 43.1 kt, and 34.7 kt in 2015, respectively, while those
      for household cooking totaled 1.55 kt, 4.02 kt, 6.55 kt, and 3.99 kt. Emissions
      from household heating contributed to~70% of PM2.5 and ~60% of SO2 emissions in
      winter. Additionally, downtown Beijing is surrounded by polluted suburbs. A coal
      forbiddance policy (e.g. "coal to gas") could gradually improve the air quality
      in urban Beijing.

PMID- 29567445
TI  - The antidepressant fluoxetine alters mechanisms of pre- and post-copulatory
      sexual selection in the eastern mosquitofish (Gambusia holbrooki).
AB  - Contamination of aquatic habitats with pharmaceuticals is a major environmental
      concern. Recent studies have detected pharmaceutical pollutants in a wide array
      of ecosystems and organisms, with many of these contaminants being highly
      resistant to biodegradation and capable of eliciting sub-lethal effects in non
      target species. One such pollutant is fluoxetine, a widely prescribed
      antidepressant, which is frequently detected in surface waters globally and can
      alter physiology and behaviour in aquatic organisms. Despite this, relatively
      little is known about the potential for fluoxetine to disrupt mechanisms of
      sexual selection. Here, we investigate the impacts of 30-day exposure to two
      environmentally realistic levels of fluoxetine (low and high) on mechanisms of
      pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia
      holbrooki). We tested 1) male mating behaviour in the absence or presence of a
      competitor male, and 2) sperm quality and quantity. We found that high-fluoxetine
      exposure increased male copulatory behaviour in the absence of a competitor,
      while no effect was detected under male-male competition. Further, fluoxetine
      exposure at both concentrations increased total sperm count relative to males
      from the control group, while no significant change in sperm quality was
      observed. Lastly, low-fluoxetine males showed a significant reduction in
      condition index (mass relative to length). Our study is the first to show altered
      mechanisms of both pre- and post-copulatory sexual selection in an aquatic
      species resulting from environmentally realistic fluoxetine exposure,
      highlighting the capacity of pharmaceutical pollution to interfere with sensitive
      reproductive processes in wildlife.

PMID- 29567446
TI  - Melamine and its derivatives in dog and cat urine: An exposure assessment study.
AB  - Melamine is a nitrogen-containing organic compound that is used in a wide range
      of products, including paints, plastics, and paper, as a flame retardant. A few
      studies have reported the occurrence of melamine and its derivatives in pet food,
      following a number of deaths of cats and dogs from kidney failure in 2007, which
      was attributed to melamine contamination in ingredients used in pet food.
      Nevertheless, studies that report the occurrence of melamine and its derivatives
      in pet urine are scarce. In this study, we measured melamine and its derivatives
      (i.e., ammeline, ammelide, and cyanuric acid) in dog (n = 30) and cat (n = 30)
      urine collected from Albany, New York, USA, during March through July 2017. The
      mean (+/-SD) concentrations of melamine, ammeline, ammelide, and cyanuric acid in
      dog urine were 21.1 +/- 51.2, 2.3 +/- 3.8, 9.9 +/- 1 0.4, and 79.0 +/- 105 ng/mL,
      respectively; the corresponding concentrations in cats were 21.4 +/- 26.1, 1.2 +/
      2.5, 6.1 +/- 3.9, and 105 +/- 94.6 ng/mL, respectively. No significant
      difference was observed in urinary concentrations of melamine derivatives between
      cats and dogs. Age and gender were important determinants of the concentrations
      of the target chemicals in cats and dogs. Cumulative daily intake of melamine and
      its derivatives was calculated on the basis of urinary concentrations and was
      found to be 10-500-fold below the tolerable daily intake.

PMID- 29567448
TI  - GL3.3, a Novel QTL Encoding a GSK3/SHAGGY-like Kinase, Epistatically Interacts
      with GS3 to Produce Extra-long Grains in Rice.

PMID- 29567447
TI  - Plant uptake and availability of antimony, lead, copper and zinc in oxic and
      reduced shooting range soil.
AB  - Shooting ranges polluted by antimony (Sb), lead (Pb), copper (Cu) and zinc (Zn)
      are used for animal grazing, thus pose a risk of contaminants entering the food
      chain. Many of these sites are subject to waterlogging of poorly drained soils.
      Using field lysimeter experiments, we compared Sb, Pb, Cu and Zn uptake by four
      common pasture plant species (Lolium perenne, Trifolium repens, Plantago
      lanceolata and Rumex obtusifolius) growing on a calcareous shooting range soil
      under waterlogged and drained conditions. To monitor seasonal trends, the same
      plants were collected at three times over the growing season. Additionally,
      variations in soil solution concentrations were monitored at three depths over
      the experiment. Under reducing conditions, soluble Sb concentrations dropped from
      ~50 MUg L-1 to ~10 MUg L-1, which was attributed to the reduction of Sb(V) to
      Sb(III) and the higher retention of the trivalent species by the soil matrix.
      Shoot Sb concentrations differed by a factor of 60 between plant species, but
      remained at levels <0.3 MUg g-1. Despite the difference in soil solution
      concentrations between treatments, total Sb accumulation in shoots for plants
      collected on the waterlogged soil did not change, suggesting that Sb(III) was
      much more available for plant uptake than Sb(V), as only 10% of the total Sb was
      present as Sb(III). In contrast to Sb, Pb, Cu and Zn soil solution concentrations
      remained unaffected by waterlogging, and shoot concentrations were significantly
      higher in the drained treatment for many plant species. Although showing an
      increasing trend over the season, shoot metal concentrations generally remained
      below regulatory values for fodder plants (40 MUg g-1 Pb, 150 MUg g-1 Zn, 15-35
      MUg g-1 Cu), indicating a low risk of contaminant transfer into the food chain
      under both oxic and anoxic conditions for the type of shooting range soil
      investigated in this study.

PMID- 29567449
TI  - A Novel QTL qTGW3 Encodes the GSK3/SHAGGY-Like Kinase OsGSK5/OsSK41 that
      Interacts with OsARF4 to Negatively Regulate Grain Size and Weight in Rice.
AB  - Grain size and shape are important determinants of grain weight and yield in
      rice. Here, we report a new major quantitative trait locus (QTL), qTGW3, that
      controls grain size and weight in rice. This locus, qTGW3, encodes OsSK41 (also
      known as OsGSK5), a member of the GLYCOGEN SYNTHASE KINASE 3/SHAGGY-like family.
      Rice near-isogenic lines carrying the loss-of-function allele of OsSK41 have
      increased grain length and weight. We demonstrate that OsSK41 interacts with and
      phosphorylates AUXIN RESPONSE FACTOR 4 (OsARF4). Co-expression of OsSK41 with
      OsARF4 increases the accumulation of OsARF4 in rice protoplasts. Loss of function
      of OsARF4 results in larger rice grains. RNA-sequencing analysis suggests that
      OsARF4 and OsSK41 repress the expression of a common set of downstream genes,
      including some auxin-responsive genes, during rice grain development. The loss-of
      function form of OsSK41 at qTGW3 represents a rare allele that has not been
      extensively utilized in rice breeding. Suppression of OsSK41 function by either
      targeted gene editing or QTL pyramiding enhances rice grain size and weight.
      Thus, our study reveals the important role of OsSK41 in rice grain development
      and provides new candidate genes for genetic improvement of grain yield in rice
      and perhaps in other cereal crops.

PMID- 29567450
TI  - TGW3, a Major QTL that Negatively Modulates Grain Length and Weight in Rice.

PMID- 29567451
TI  - Pm21 from Haynaldia villosa Encodes a CC-NBS-LRR Protein Conferring Powdery
      Mildew Resistance in Wheat.

PMID- 29567452
TI  - Plant Genome Editing Using FnCpf1 and LbCpf1 Nucleases at Redefined and Altered
      PAM Sites.

PMID- 29567453
TI  - Expanding the Scope of CRISPR/Cpf1-Mediated Genome Editing in Rice.

PMID- 29567454
TI  - Pm21, Encoding a Typical CC-NBS-LRR Protein, Confers Broad-Spectrum Resistance to
      Wheat Powdery Mildew Disease.

PMID- 29567455
TI  - Modeling life course pathways from adverse childhood experiences to adult mental
      health.
AB  - Although the association between adverse childhood experiences (ACEs) and adult
      mental health is becoming well established, less is known about the complex and
      multiple pathways through which ACEs exert their influence. Growing evidence
      suggests that adversity early in life conveys not only early impacts, but also
      augments risk of stress-related life course cascades that continue to undermine
      health. The present study aims to test pathways of stress proliferation and
      stress embodiment processes linking ACEs to mental health impairment in
      adulthood. Data are from the 2011 Behavioral Risk Factor Surveillance Survey, a
      representative sample of Washington State adults ages 18 and over (N = 14,001).
      Structural equation modeling allowed for testing of direct and indirect effects
      from ACEs though low income status, experiences of adversity in adulthood, and
      social support. The model demonstrated that adult low income, social support and
      adult adversity are in fact conduits through which ACEs exert their influence on
      mental health impairment in adulthood. Significant indirect pathways through
      these variables supported hypotheses that the effect of ACEs is carried through
      these variables. This is among the first models that demonstrates multiple stress
      related life course pathways through which early life adversity compromises adult
      mental health. Discussion elaborates multiple service system opportunities for
      intervention in early and later life to interrupt direct and indirect pathways of
      ACE effects.

PMID- 29567456
TI  - Are negative/unrealistic parent descriptors of infant attributes associated with
      physical abuse?
AB  - Parents' perceptions of child behavior influence their responses to the child and
      may be important predictors of physical abuse. We examined whether infants 12
      months of age or younger who were described with negative or developmentally
      unrealistic words were more likely than other infants to have been physically
      abused. As part of a prospective observational multicenter study investigating
      bruising and familial psychosocial characteristics, parents were asked to (1)
      describe their child's personality, and (2) list three words to describe their
      child. Four independent raters coded parent responses using a qualitative content
      analysis, identifying descriptors of infants and classifying each as positive,
      neutral, or negative/unrealistic. A medical expert panel, blinded to the
      psychosocial data, separately categorized each case as abuse or accident. We then
      analyzed the potential association between negative/unrealistic descriptors and
      abusive injury. Of 185 children enrolled, 147 cases (79%) were categorized as
      accident and 38 (21%) as abuse. Parents used at least one negative/unrealistic
      descriptor in 35/185 cases (19%), while the remaining 150 cases (81%) included
      only positive or neutral descriptors. Of the infants described with
      negative/unrealistic words, 60% were abused, compared to 11% of those described
      with positive or neutral words (p < .0001; age group-adjusted OR = 9.95; 95%
      confidence interval [3.98, 24.90]). Though limited by sample-size, this pilot
      study informs future work to create a screening tool utilizing
      negative/unrealistic descriptors in combination with other predictive factors to
      identify infants at high risk for physical child abuse.

PMID- 29567457
TI  - Child maltreatment in rural southern counties: Another perspective on race,
      poverty and child welfare.
AB  - Building on research that has identified community characteristics associated
      with child maltreatment, this study investigates the adequacy and equity of the
      child welfare response at the county level. The study focuses on states in the
      U.S. south with demographic characteristics that make it possible to disentangle
      county racial composition from county rurality. County-level child maltreatment
      data were merged with data from the U.S. Census and other publicly-available
      sources for the 354 counties in four southern states. Results from multiple
      regression models indicated that, despite a greater preponderance of risk factors
      typically associated with child maltreatment, rural, majority African-American
      counties had lower rates of reported and substantiated child maltreatment
      compared to other southern counties. Cross-sectional results were consistent
      across three years: 2012, 2013, and 2014. The findings suggest that children and
      families in rural, majority African-American counties in the South may not be
      receiving adequate or equitable responses from the formal child welfare system.

PMID- 29567458
TI  - Synthesis and antikinetoplastid evaluation of bis(benzyl)spermidine derivatives.
AB  - This study describes the synthesis and the biological evaluation of twenty-four
      original bis(benzyl)spermidines. Structural modifications of the polyamine
      scaffold were performed in order to avoid easily metabolized bonds. Some
      bis(benzyl)polyamine derivatives have demonstrated promising activity in vitro
      against Trypanosoma brucei gambiense and Leishmania donovani. From the enzymatic
      experiments on trypanothione reductase, we observed that this enzyme was not
      targeted by our compounds. In vivo evaluation on Swiss mice model infected by T.
      b. gambiense or L. donovani was done with the most interesting compound of the
      series.

PMID- 29567459
TI  - 1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and
      HDAC.
AB  - A series of 1-aroylindoline-hydroxamic acids have been synthesized in the present
      study. The results of the biological evaluation led to the identification of
      compound 12 as dual HDAC6/HSP90 inhibitor. Compound 12 displayed striking
      inhibitory effects towards the HDAC6 isoform and HSP 90 protein with IC50 values
      of 1.15 nM (HDAC6) and 46.3 nM (HSP90). Compound 12 also exhibited 113, 139 and
      246 fold higher selectivity for HDAC6 over HDAC 1, HDAC 3 and HDAC 8 isoforms and
      was endowed with significant cytotoxic effects with GI50 values ranging 1.04-1.61
      MUM against lung A549, colorectal HCT116, leukemia HL60, and EGFR T790M mutant
      lung H1975 cell lines. Another interesting finding of the study was substantial
      cytotoxic effects of compounds particularly against lung H1975 (NSCLC) cell lines
      with IC50 = 0.26 MUM which may be mediated through HSP90 inhibition. Compound 8
      as such was devoid of HDAC inhibitory activity.

PMID- 29567460
TI  - Knowledge of the risk factors and symptoms associated with endometrial cancer in
      British South Asian and British White women.
AB  - OBJECTIVE: To explore differences in the background knowledge of Endometrial
      Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC)
      between British White (BW) and British South Asian (BSA) women who had undergone
      treatment for stage I endometrial cancer within the past 3-years. STUDY DESIGN:
      Face-to-face, semi-structured interviews exploring knowledge; diagnosis;
      treatment; follow-up; and survivorship were undertaken and analysed using
      Thematic Analysis. RESULTS: Twenty-one women were interviewed (13 BW and 8 BSA).
      BW and BSA women reported similar views, experiences and concerns with regards to
      EC. Knowledge appeared to differ amongst the two groups with BSA women reporting
      being more aware that unscheduled vaginal bleeding could be associated with a
      malignancy but having lower levels of knowledge of the risk factors that can lead
      to EC, compared to BW women. There was a lack of understanding of the difference
      between cervical cancer and EC and as a result, many women reported taking
      reassurance from negative cervical cytology as excluding EC. There was also the
      misconception amongst some of the women that there was a link between sexual
      behaviour and EC. Women from both groups used the lay healthcare system to
      discuss their situation/symptoms, however BSA women reported to have specifically
      sought out women within their social network who had previously undergone
      treatment for EC. CONCLUSIONS: Greater effort is needed to raise awareness in
      both the BW/BSA communities of the symptoms associated with EC that should prompt
      medical review. Educational efforts are required to overcome the reported
      perception that EC is synonymous with cervical cancer and cannot be detected by
      cervical screening.

PMID- 29567461
TI  - PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of
      2 randomized trials.
AB  - BACKGROUND: PrEP-001 Nasal Powder, a proprietary formulation of polyriboinosinic
      and polyribocytidylic acid effectively elicits a cellular innate immune response
      in nasal epithelium. The aim of these 2 studies was to investigate the safety and
      efficacy of PrEP-001 prophylaxis against rhinovirus (HRV-A16) and influenza-A
      (H3N2-IAV). METHODS: Healthy subjects randomly received 2 doses of PrEP-001 or
      placebo, 48 and 24 h pre-challenge with 10 TCID50 of HRV-A16 (Study 1) or H3N2
      IAV (Study 2). RESULTS: In Study 1, PrEP-001 reduced median total symptom score
      from 38.5 to 4.5 (p = 0.004), median symptom duration from 6.0 to 1.7 days and
      median mucus production from 15 g to 3 g. The percentage of subjects classified
      as ill was reduced 3-fold (placebo 73%, PrEP-001 23%, p = 0.002). In Study 2,
      PrEP-001 reduced median total symptom score from 8.0 to 4.1 (p = 0.021), median
      symptom duration from 4.6 to 3.7 days and median mucus production from 3.6 g to
      1.5 g. The percentage of subjects classified as ill was reduced 2-fold (placebo
      48%, PrEP-001 24%, p = 0.064). PrEP-001 reduced peak viral shedding in both
      studies, as assessed by qRT-PCR of nasal lavage. Seroconversion rates were
      comparable between placebo and PrEP-001 (Study 1: 77% [both arms]; Study 2:
      placebo 73%, PrEP-001 80%). PrEP-001 was well-tolerated, with no clinically
      significant adverse events. CONCLUSIONS: PrEP-001 reduced the number of
      individuals with clinical illness and attenuated severity and duration of HRV-A16
      and H3N2-IAV infections without compromising seroconversion, and was well
      tolerated. This supports further evaluation of PrEP-001 as a potential pan-viral
      prophylaxis for upper respiratory tract infections. CLINICAL TRIAL REGISTRATION:
      Study 1, HRV-A16 study: EudraCT Number 2012-005579-14 (study conducted before
      ClinicalTrials.gov registration required). Study 2, H3N2-IAV study: EudraCT
      Number 2015-002895-26 and ClinicalTrials.gov: NCT03220048.

PMID- 29567462
TI  - Postresuscitation myocardial dysfunction or a variant of takotsubo
      cardiomyopathy?

PMID- 29567463
TI  - Long-term quality of life of caregivers of cardiac arrest survivors and the
      impact of witnessing a cardiac event of a close relative.
AB  - BACKGROUND: The incidence of cardiac arrest is high, with a poor survival rate of
      8-14%. Currently, only limited evidence is available about long-term consequences
      of cardiac arrest on quality of life of caregivers. AIMS: First, to determine the
      level of daily functioning and quality of life in caregivers of cardiac arrest
      survivors two years after the cardiac arrest. Second, to study the long-term
      impact of witnessing the event of a cardiac arrest. METHODS: A longitudinal
      cohort study including caregivers of cardiac arrest survivors. Participants
      received a questionnaire at home. Outcome variables were instrumental daily
      activities(FAI), emotional functioning(HADS), fatigue(FSS), caregiver
      strain(CSI), impact of event(IES), and quality of life(SF36). RESULTS: 57
      caregivers (89% female, age 56,9 +/- 12 years) participated. Two years after the
      cardiac arrest, quality of life of caregivers equals that of the general
      population, although almost 30% still scored high on the Impact of Events Scale.
      Mean IES-, FSS-, CSI and FAI-scores were increased as compared to the general
      population (P < 0.001). Two years after the cardiac arrest, caregivers that
      witnessed the resuscitation (IES = 23.6 +/- 14.9) still experienced significantly
      more trauma related stress than caregivers that did not witness the resuscitation
      (11.9 +/- 12.5; p < 0.01). CONCLUSIONS: Two years after the cardiac arrest,
      quality of life of caregivers is quite good, but almost one third of the
      caregivers still experience a high level of trauma-related stress, especially in
      those that witnessed the resuscitation. Future research will have to focus on the
      effectiveness of support programs for caregivers of survivors of cardiac arrest.

PMID- 29567464
TI  - Parent perspectives on the clinician-client relationship in speech-language
      treatment for children.
AB  - Few studies have explored clinician-client relationships in speech-language
      treatment for children, although evidence indicates that these relationships may
      be important. Parents play a unique role in clinician-client relationships and
      their views have yet to be considered in the speech-language pathology
      literature. This study explored parents' perspectives on the clinician-client
      relationship in speech-language treatment for children using both quantitative
      and qualitative information. An online survey collected responses from 159
      parents with children enrolled in speech-language services. Respondents were
      asked to complete a rating of the clinician-client relationship, provide
      information on length of treatment and treatment setting, and respond to open
      ended questions about what enhances the clinician-client relationship. Length of
      treatment was unrelated to the parent rating of the clinician-client
      relationship. However, ratings did vary by treatment setting; parents of children
      enrolled in treatment services in schools provided lower ratings than parents
      with children enrolled in other settings. Thematic analysis of parent views on
      what enhances the clinician-client relationship yielded four main themes:
      qualities of the speech-language pathologist (SLP), session characteristics, the
      child-SLP bond, and communication. The most frequent subthemes in the analysis
      related to characteristics of the sessions: the integration of play and fun, and
      a child-oriented approach to sessions. These results provide insight into the
      development of clinician-client relationships in children's speech-language
      treatment, with implications for both clinicians and researchers.

PMID- 29567465
TI  - Perceived listener effort as an outcome measure for disordered speech.
AB  - PURPOSE: Perceived listening effort is a perceptual dimension used to identify
      the amount of work necessary to understand disordered speech. The purpose of this
      study was to investigate the utility of perceived listening effort to provide
      unique information about disordered speech. The relationships between perceived
      listening effort and two current outcome measures (speech acceptability,
      intelligibility) were examined for listeners rating electrolaryngeal speech,
      along with their reliability and intra-rater agreement. METHODS: Ten healthy male
      speakers read low-context sentences using an electrolarynx. Twenty-five
      inexperienced listeners orthographically transcribed and rated the stimuli for
      perceived listening effort and speech acceptability using a visual analog scale.
      Strict reliability and agreement criteria were set. RESULTS: Perceived listening
      effort was moderately to strongly correlated with intelligibility (r = -0.76) and
      acceptability (r = -0.80), each of which contributed uniquely to ratings of
      perceived listening effort. However, only 17 listeners met stringent reliability
      and agreement criteria. CONCLUSIONS: Ratings of perceived listening effort may
      provide unique information about the communicative success of individuals with
      communication disorders. There is great variability, however, among inexperienced
      listeners' perceptual ratings of electrolaryngeal speech. Future research should
      investigate variables that may affect perceived listening effort specifically and
      auditory-perceptual ratings in general.

PMID- 29567466
TI  - Is there a mismatch between policies to curtail physician opioid prescribing and
      what we know about changing physician behavior?

PMID- 29567467
TI  - The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced
      by T-2 toxin.
AB  - T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2
      toxin is involved in G1 phase arrest in several cell lines but molecular
      mechanism is still not clear. In present study, we used rat pituitary GH3 cells
      to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40
      nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a
      considerable increase in reactive oxygen species (ROS) as well as loss in
      mitochondrial membrane potential (?Ym) upon exposure to the T-2 toxin. Flow
      cytometry showed a significant time-dependent increase in percentage of apoptotic
      cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal
      DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA
      damage with a time-dependent significant increased expression of p53 favors the
      apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell
      cycle analysis by flow cytometry revealed a time-dependent increase ofG1 cell
      population along with the significant time-dependent up-regulation of mRNA and
      protein expression of p16 and p21 and significant down-regulation of cyclin D1,
      CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology
      of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and
      the cell nucleus. These findings for the first time demonstrate that T-2 toxin
      induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along
      with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade
      interaction, resulting in apoptosis in GH3 cells.

PMID- 29567468
TI  - Ants impact the composition of the aquatic macroinvertebrate communities of a
      myrmecophytic tank bromeliad.
AB  - In an inundated Mexican forest, 89 out of 92 myrmecophytic tank bromeliads
      (Aechmea bracteata) housed an associated ant colony: 13 sheltered Azteca serica,
      43 Dolichoderus bispinosus, and 33 Neoponera villosa. Ant presence has a positive
      impact on the diversity of the aquatic macroinvertebrate communities (n=30
      bromeliads studied). A Principal Component Analysis (PCA) showed that the
      presence and the species of ant are not correlated to bromeliad size, quantity of
      water, number of wells, filtered organic matter or incident radiation. The PCA
      and a generalized linear model showed that the presence of Azteca serica differed
      from the presence of the other two ant species or no ants in its effects on the
      aquatic invertebrate community (more predators). Therefore, both ant presence and
      species of ant affect the composition of the aquatic macroinvertebrate
      communities in the tanks of A. bracteata, likely due to ant deposition of feces
      and other waste in these tanks.

PMID- 29567469
TI  - Promoting degradation of 2,4-dichlorophenoxyacetic acid with fermentative
      effluents from hydrogen-producing reactor.
AB  - This research aims to identifying the potential effect of using a hydrogen
      producing reactor's effluent as an enrichment amendment for enhancing the
      degradation rates of 2,4-dichlorophenoxyacetic acid (2,4-D) during the
      bioremediation of contaminated paddy soils. The results showed that addition of
      the effluents to 2,4-D- degrading enrichment culture enhanced (up to 1.3-fold)
      the degradation rate constant of 2,4-D. The enhancement effect most probably
      resulted from the co-metabolic degradation of 2,4-D facilitated by volatile fatty
      acids (e.g., acetate, propionate, and butyrate) in the effluents which served as
      the beneficial substrates. Results from DNA sequencing analysis showed that the
      effluent additions shifted the bacterial community composition in the enrichment
      culture. Dechloromonas and Clostridium were two dominant bacterial genera
      involved in 2,4-D degradation. The findings will make a substantial contribution
      to remediation of soils contaminated with 2,4-D.

PMID- 29567470
TI  - Mass fluxes per capita of organic contaminants from on-site sewage treatment
      facilities.
AB  - This study is the first attempt to quantify environmental fluxes per capita of
      organic contaminants discharged from on-site sewage treatment facilities (OSSFs)
      in affected recipients. Five sites were monitored around the River Fyris in
      Sweden: three mainly affected by OSSFs and two mainly affected by municipal
      sewage treatment plants (STPs). Gas chromatography-mass spectrometry was used to
      determine environmental concentrations of 30 anthropogenic contaminants,
      including organophosphorus compounds, rubber and plastic additives, UV
      stabilizers, fragrances, surfactant ingredients and polycyclic aromatic
      hydrocarbons. Uni- and multivariate statistical analysis of the most frequently
      detected contaminants showed that median fluxes per capita of tris(1,3-dichloro-2
      propyl) phosphate, tris(1-chloro-2-propyl) phosphate, tris(2-chloroethyl)
      phosphate, and n-butylbenzene sulfonamide were similar at OSSF and STP sites, but
      the mass fluxes per capita of tris-(2-butoxyethyl) phosphate, 2
      (methylthio)benzothiazole, and galaxolide, were significantly lower (~2-3-fold)
      at OSSF sites than at STP sites (Mann-Whitney, alpha = 0.05). Differences between
      these sites were larger in samples collected in summer and autumn than in samples
      collected in winter. Deviations likely originated from differences in fate
      processes and distances between source and sampling sites. Further studies are
      needed to characterize mass fluxes per capita of contaminants in waters that
      directly receive discharges from OSSFs.

PMID- 29567471
TI  - Fluoride-induced alterations of synapse-related proteins in the cerebral cortex
      of ICR offspring mouse brain.
AB  - Fluoride (F) exposure causes cognitive dysfunction in humans and animals.
      However, the precise molecular mechanisms by which fluoride exerts its neurotoxic
      effects are poorly understood. In this study, an animal model of fluoride
      exposure was created by providing ICR mice were treated with vehicle F at a dose
      of 0 (control group), 50 (low-fluoride group) or 100 mg/L (high-fluoride group)
      in water for one month. After the mice mated, parents and offspring were treated
      and maintained under these conditions. The cognitive abilities of the mice were
      examined using a Morris water maze test. Results indicated that fluoride exposure
      significantly prolonged the escape latency period and decreased the number of
      crossings in a particular zone. Histopathologic analysis revealed the shrinkage
      and fragmentation of glial cells in the fluoride-treated groups. Pyramidal cells
      in the cerebral cortices of fluoride-treated groups were fewer than those of the
      control group. The expression of microtubule-associated protein 2 (MAP2) and
      synaptic proteins of the cerebral cortex in mouse offspring was assayed using RT
      PCR and Western blot. Fluoride exposure possibly induced a significantly
      decreased expression of MAP2, synaptophysin (SYP) and developmentally regulated
      brain protein (Dbn) at protein and mRNA levels. Glutamate receptor (N-methyl-d
      aspartate receptor, NMDAR) was also expressed, and this finding was consistent
      with the reduced MAP2, SYP and Dbn expression. Therefore, fluoride-mediated
      reduction in cognitive dysfunction is likely caused by the disruption of the
      expression of these synapse-associated proteins, resulting in attenuated neuronal
      functioning.

PMID- 29567472
TI  - SOAT1 deficiency attenuates atherosclerosis by regulating inflammation and
      cholesterol transportation via HO-1 pathway.
AB  - Sterol O-acyltransferase 1 (SOAT1) is a key enzyme for cholesteryl ester
      biosynthesis. The objective of the present study is to investigate the role and
      underlying molecular mechanisms of SOAT1 in atherosclerosis. Our results
      indicated that SOAT1 was highly expressed in endothelial cells of atherosclerotic
      lesions in human patients with atherosclerosis and in apolipoprotein E deficient
      (ApoE-/-) mice fed with high fat diet (HFD). We established a model of
      atherosclerosis using ApoE and SOAT1 gene double knockout (ApoE-/-SOAT1-/-) mice.
      SOAT1-/- alleviated HFD-induced and spontaneously developed atherosclerotic
      lesions in ApoE-/- mice, accompanied with the reduced triglyceride (TG), total
      cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), while the
      enhanced high-density lipoprotein-cholesterol (HDL-C) in serum of ApoE-/- mice.
      SOAT1-/- decreased collagen accumulation in the lesions. SOAT1-/- reduced
      macrophage infiltration and suppressed inflammation in ApoE-/- mice fed with HFD,
      as evidenced by the decreased expressions of pro-inflammatory cytokines,
      including interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha (TNF
      alpha). Of importance, SOAT1-/--attenuated inflammation was along with the
      inactivation of beta-catenin and nuclear factor kappa B (NF-kappaB) ApoE-/- mice.
      Moreover, oxidative stress observed in ApoE-/- mice was inactivated by SOAT1
      double knockout. In addition, expression levels of fatty acid synthase (FAS),
      stearoyl-CoA desaturase 1 (SCD1), protein convertase subtilisin/kexin type 9
      (PCSK 9) and sterol regulatory element-binding protein-1c (SREBP-1c) were
      decreased in liver, peritoneal macrophages and abdominal aortas of SOAT1-knockout
      ApoE-/- mice. In contrast, SOAT1-/- displayed improved expressions of peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) and lipoxygenase (LOX)-alpha
      in liver, peritoneal macrophages and abdominal aortas of ApoE-/- mice. Of note,
      the in vitro study, oxidized low-density lipoprotein (ox-LDL) incubation reduced
      heme oxygenase (HO-1) expressions in human umbilical vein endothelial cells
      (HUVECs), which was improved by SOAT1 knockdown. Pre-treatment of sn
      protoporphyrin (SnPP), an important HO-1 inhibitor, abolished the role of SOAT1
      inhibition in suppressing inflammation and abnormal cholesterol transportation.
      These results indicated that SOAT1 deficiency protected against atherosclerosis
      progression via inhibiting cholesterol transportation in ApoE-/- mice, which was,
      at least partly, dependent on HO-1 expressions.

PMID- 29567473
TI  - Bruton's tyrosine kinase regulates TLR7/8-induced TNF transcription via nuclear
      factor-kappaB recruitment.
AB  - Tumour necrosis factor (TNF) is produced by primary human macrophages in response
      to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and
      endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor
      (TLR) signalling. However, uncontrolled TNF production can be deleterious and
      hence it is tightly controlled at multiple stages. We have previously shown that
      Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP
      Kinase by stabilising TNF messenger RNA. Using both gene over-expression and
      siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF
      production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser
      536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human
      macrophages. These data show an important role for Btk in TLR7/8 mediated TNF
      production and reveal distinct differences for Btk in TLR4 versus TLR7/8
      signalling.

PMID- 29567474
TI  - Treacher Collins syndrome 3 (TCS3)-associated POLR1C mutants are localized in the
      lysosome and inhibits chondrogenic differentiation.
AB  - Treacher Collins syndrome (TCS) is a craniofacial developmental disorder whose
      key feature is a combination of symptoms. For example, a patient could have
      bilateral downward slanting of the palpebral fissures, colobomas of the lower
      eyelids, hypoplasia of the facial bones, cleft palate, malformation of the
      external ears, and atresia of the external auditory canals. TCS3 is caused by
      mutations of the polr1c gene, which encodes RNA polymerase I and III subunit C
      (POLR1C). There have been two known missense mutations (Arg279-to-Gln [R279Q] and
      Arg279-to-Trp [R279W]) at the Arg-279 position. However, it remains to be
      clarified whether or how both or each individual mutation affects the cellular
      properties of POLR1C. Here we show that TCS3-associated missense mutations cause
      aberrant intracellular localization of POLR1C, inhibiting chondrogenic
      differentiation. The wild type POLR1C is normally localized in the nuclei. The
      R279Q or R279W mutant is primarily found to be localized in the lysosome.
      Expression of the R279Q or R279W mutant in mouse chondrogenic ATDC5 cells
      decreases phosphorylation of 4E-BP1 and ribosomal S6 proteins, which belong to
      the mammalian target of rapamycin (mTOR) signaling involved in critical roles in
      the lysosome. Furthermore, expression of the R279Q or R279W mutant inhibits
      chondrogenic differentiation in ATDC5 cells. Taken together, TCS3-associated
      mutation leads to the localization of POLR1C into the lysosome and inhibits
      chondrogenic differentiation, possibly explaining a portion of the pathological
      molecular basis underlying Treacher Collins syndrome.

PMID- 29567475
TI  - Involvement of phosphatidylinositol-3 kinase/Akt/mammalian target of
      rapamycin/peroxisome proliferator-activated receptor gamma pathway for induction
      and maintenance of neuropathic pain.
AB  - Peripheral nerve injury induces neuropathic pain, which is characterized by the
      tactile allodynia and thermal hyperalgesia. N-type voltage-dependent Ca2+ channel
      (VDCC) plays pivotal roles in the development of neuropathic pain, since mice
      lacking Cav2.2, the pore-forming subunit of N-type VDCC, show greatly reduced
      symptoms of both tactile allodynia and thermal hyperalgesia. Our study on gene
      expression profiles of the wild-type and N-type VDCC knockout (KO) spinal cord
      and several pain-related brain regions after spinal nerve ligation (SNL) injury
      revealed altered expression of genes encoding catalytic subunits of
      phosphatidylinositol-3 kinase (PI3K). PI3K/Akt/mammalian target of rapamycin
      (PI3K/Akt/mTOR) signaling is considered to be very important for cancer
      development and drugs targeting the molecules in this pathway have been tested in
      oncology trials. In the present study, we have tested whether the changes in
      expression of molecules in this pathway in mice having spinal nerve injury are
      causally related to neuropathic pain. Our results suggest that spinal nerve
      injury induces activation of N-type VDCC and the following Ca2+ entry through
      this channel may change the expression of genes encoding PI3K catalytic subunits
      (p110alpha and p110gamma), Akt, retinoid X receptor alpha (RXRalpha) and
      RXRgamma. Furthermore, the blockers of the molecules in this pathway are found to
      be effective in reducing neuropathic pain both at the spinal and at the
      supraspinal levels. Thus, the activation of PI3K/Akt/mTOR/peroxisome proliferator
      activated receptor gamma (PPARgamma) pathway would be a hallmark of the induction
      and maintenance of neuropathic pain.

PMID- 29567476
TI  - Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with
      tumor progression and poor prognosis in lung adenocarcinoma.
AB  - Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+-ATPase that plays a
      key role in mitotic checkpoint complex inactivation and is associated with the
      progression of several cancers. However, its role in lung adenocarcinogenesis
      remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple
      lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression
      is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier
      analysis revealed that heightened TRIP13 expression is associated with lower
      overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation,
      clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in
      vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth
      inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts
      with a protein network associated with dsDNA break repair and PI3K/Akt signaling.
      TRIP13 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which
      suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic
      BadSer136 and cleaved caspase-3 while upregulating survivin. In conclusion,
      heightened TRIP13 expression appears to promote lung adenocarcinoma tumor
      progression and displays potential as a therapeutic target or biomarker for lung
      adenocarcinoma.

PMID- 29567477
TI  - The blocking of aquaporin-3 (AQP3) impairs extravillous trophoblast cell
      migration.
AB  - Several aquaporins (AQPs) are expressed in extravillous (EVT) and villous
      trophoblast cells. Among them, AQP3 is the most abundant AQP expressed in
      chorionic villi samples from first trimester, followed by AQP1 and AQP9. Although
      AQP3 expression persists in term placentas, it is significantly decreased in
      placentas from preeclamptic pregnancies. AQP3 is involved in the migration of
      different cell types, however its role in human placenta is still unknown. Here,
      we evaluated the role of AQP3 in the migration of EVT cells during early
      gestation. Our results showed that Swan 71 cells expressed AQP1, AQP3 and AQP9
      but only the blocking of AQP3 by CuSO4 or the silencing of its expression by
      siRNA significantly attenuates EVT cell migration. Our work provides evidence
      that AQP3 is required for EVT cell migration and suggests that an altered
      expression of placental AQP3 may produce failures in placentation such as in
      preeclampsia.

PMID- 29567478
TI  - Molecular association model of PPARalpha and its new specific and efficient
      ligand, pemafibrate: Structural basis for SPPARMalpha.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a ligand
      activated transcription factor involved in the regulation of lipid homeostasis
      and improves hypertriglyceridemia. Pemafibrate is a novel selective PPARalpha
      modulator (SPPARMalpha) that activates PPARalpha transcriptional activity. Here,
      we computationally constructed the structure of the human PPARalpha in a complex
      with pemafibrate, along with that of hPPARalpha complexed with the classical
      fenofibrate, and studied their interactions quantitatively by using the first
      principles calculations-based fragment molecular orbital (FMO) method.
      Comprehensive structural and protein-ligand binding elucidation along with the in
      vitro luciferase analysis let us to identify pemafibrate as a novel SPPARMalpha.
      Unlike known fibrate ligands, which bind only with the arm I of the Y-shaped
      ligand binding pocket, the Y-shaped pemafibrate binds to the entire cavity
      region. This lock and key nature causes enhanced induced fit in pemafibrate
      ligated PPARalpha. Importantly, this selective modulator allosterically changes
      PPARalpha conformation to form a brand-new interface, which in turn binds to
      PPARalpha co-activator, PGC-1alpha, resulting in the full activation of
      PPARalpha. The structural basis for the potent effects of pemafibrate on
      PPARalpha transcriptional activity predicted by the in silico FMO methods was
      confirmed by in vitro luciferase assay for mutants. The unique binding mode of
      pemafibrate reveals a new pattern of nuclear receptor ligand recognition and
      suggests a novel basis for ligand design, offering cues for improving the binding
      affinity and selectivity of ligand for better clinical consequences. The findings
      explain the high affinity and efficacy of pemafibrate, which is expected to be in
      the clinical use soon.

PMID- 29567479
TI  - Loop engineering reveals the importance of active-site-decorating loops and
      gating residue in substrate affinity modulation of arginine deiminase (an anti
      tumor enzyme).
AB  - Protein engineering of enzyme loop regions is an effective strategy to improve
      enzymatic properties. Previous studies that aimed to boost the activity of PpADI
      (an arginine deiminase from Pseudomonas plecoglossicida) under physiological
      conditions yielded several significantly improved variants that harbor
      substitutions predominantly located in active-site-decorating loops. A multi-site
      saturation mutagenesis at four positions in loop 1 (37, 38, 42, and 43) and three
      positions in loop 4 (402, 403, and 404) was performed to elucidate the importance
      of these loops in modulating the substrate affinity of PpADI. The identified
      "best" variant (M6-L1-4) showed a decreased S0.5 ('KM') of 0.48 mM compared with
      the parent M6 (0.81 mM). Subsequently, a rational design to recombine beneficial
      substitutions within loops 1 and 4 yielded variant L6 with a substantially
      decreased S0.5 value (0.17 mM). A comprehensive simulation analysis resulted in a
      conclusion that high loop flexibility (especially the gating residue Arg400) is
      beneficial for substrate affinity due to less efficient blocking of the active
      site.

PMID- 29567480
TI  - Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.
AB  - Neurons in the adult central nervous system (CNS) have a poor intrinsic axon
      growth potential after injury, but the underlying mechanisms are largely unknown.
      Wingless-related mouse mammary tumor virus integration site (WNT) family members
      regulate neural stem cell proliferation, axon tract and forebrain development in
      the nervous system. Here we report that Wnt3 is an important modulator of axon
      regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root
      ganglion (DRG) neurons enhances or inhibits their axon regeneration ability
      respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon
      regeneration by repressing mRNA translation of the important transcription factor
      Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation
      of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG
      neurons. Taken together, these data indicate that Wnt3 is a key intrinsic
      regulator of axon growth ability of the nervous system.

PMID- 29567481
TI  - Validation of hindi translation of DSM-5 level 1 cross-cutting symptom measure.
AB  - BACKGROUND: The DSM-5 Level 1 Cross-Cutting Symptom Measure is a self- or
      informant-rated measure that assesses mental health domains which are important
      across psychiatric diagnoses. The absence of this self- or informant-administered
      instrument in Hindi, which is a major language in India, is an important
      limitation in using this scale. AIM: To translate the English version of the DSM
      5 Level 1 Cross-Cutting Symptom Measure to Hindi and evaluate its psychometric
      properties. MATERIALS AND METHODS: The study was conducted at a tertiary care
      hospital in Delhi. The DSM-5 Level 1 Cross-Cutting Symptom Measure was translated
      into Hindi using the World Health Organization's translation methodology.
      STATISTICAL ANALYSIS: Mean and standard deviation were evaluated for continuous
      variables while for categorical variables frequency and percentages were
      calculated. The translated version was evaluated for cross-language equivalence,
      test-retest reliability, internal consistency, and split half reliability.
      RESULTS: Hindi version was found to have good cross-language equivalence and test
      retest reliability at the level of items and domains. Twenty two of the 23 items
      and all the 23 items had a significant correlation (rho < 0.001) in cross
      language concordance and test-retest reliability data, respectively. The
      Cronbach's alpha was 0.95, and the Spearman-Brown Sphericity value was 0.79 for
      the Hindi version. CONCLUSION: The present study shows that cross-language
      concordance, internal consistency, split-half reliability, and test-retest
      reliability of the Hindi version of the measure are excellent. Thus, the Hindi
      version of DSM-5 Level 1 Cross-Cutting Symptom Measure as translated in this
      study is a valid instrument.

PMID- 29567482
TI  - A vectorized Levenberg-Marquardt model fitting algorithm for efficient post
      processing of cardiac T1 mapping MRI.
AB  - PURPOSE: T1 mapping is an emerging MRI research tool to assess diseased
      myocardial tissue. Recent research has been focusing on the image acquisition
      protocol and motion correction, yet little attention has been paid to the curve
      fitting algorithm. METHODS: After nonrigid registration of the image series, a
      vectorized Levenberg-Marquardt (LM) technique is proposed to improve the
      robustness of the curve fitting algorithm by allowing spatial regularization of
      the parametric maps. In addition, a region-based initialization is proposed to
      improve the initial guess of the T1 value. The algorithm was validated with
      cardiac T1 mapping data from 16 volunteers acquired with saturation-recovery (SR)
      and inversion-recovery (IR) techniques at 3T, both pre- and post-injection of a
      contrast agent. Signal models of T1 relaxation with 2 and 3 parameters were
      tested. RESULTS: The vectorized LM fitting showed good agreement with its pixel
      wise version but allowed reduced calculation time (60 s against 696 s on average
      in Matlab with 256 * 256 * 8(11) images). Increasing the spatial regularization
      parameter led to noise reduction and improved precision of T1 values in SR
      sequences. The region-based initialization was particularly useful in IR data to
      reduce the variability of the blood T1. CONCLUSIONS: We have proposed a
      vectorized curve fitting algorithm allowing spatial regularization, which could
      improve the robustness of the curve fitting, especially for myocardial T1 mapping
      with SR sequences.

PMID- 29567483
TI  - T-wave end detection using neural networks and Support Vector Machines.
AB  - BACKGROUND AND OBJECTIVE: In this paper we propose a new approach for detecting
      the end of the T-wave in the electrocardiogram (ECG) using Neural Networks and
      Support Vector Machines. METHODS: Both, Multilayer Perceptron (MLP) neural
      networks and Fixed-Size Least-Squares Support Vector Machines (FS-LSSVM) were
      used as regression algorithms to determine the end of the T-wave. Different
      strategies for selecting the training set such as random selection, k-means,
      robust clustering and maximum quadratic (Renyi) entropy were evaluated.
      Individual parameters were tuned for each method during training and the results
      are given for the evaluation set. A comparison between MLP and FS-LSSVM
      approaches was performed. Finally, a fair comparison of the FS-LSSVM method with
      other state-of-the-art algorithms for detecting the end of the T-wave was
      included. RESULTS: The experimental results show that FS-LSSVM approaches are
      more suitable as regression algorithms than MLP neural networks. Despite the
      small training sets used, the FS-LSSVM methods outperformed the state-of-the-art
      techniques. CONCLUSION: FS-LSSVM can be successfully used as a T-wave end
      detection algorithm in ECG even with small training set sizes.

PMID- 29567484
TI  - Biomedical image classification based on a cascade of an SVM with a reject option
      and subspace analysis.
AB  - Automated biomedical image classification could confront the challenges of high
      level noise, image blur, illumination variation and complicated geometric
      correspondence among various categorical biomedical patterns in practice. To
      handle these challenges, we propose a cascade method consisting of two stages for
      biomedical image classification. At stage 1, we propose a confidence score based
      classification rule with a reject option for a preliminary decision using the
      support vector machine (SVM). The testing images going through stage 1 are
      separated into two groups based on their confidence scores. Those testing images
      with sufficiently high confidence scores are classified at stage 1 while the
      others with low confidence scores are rejected and fed to stage 2. At stage 2,
      the rejected images from stage 1 are first processed by a subspace analysis
      technique called eigenfeature regularization and extraction (ERE), and then
      classified by another SVM trained in the transformed subspace learned by ERE. At
      both stages, images are represented based on two types of local features, i.e.,
      SIFT and SURF, respectively. They are encoded using various bag-of-words (BoW)
      models to handle biomedical patterns with and without geometric correspondence,
      respectively. Extensive experiments are implemented to evaluate the proposed
      method on three benchmark real-world biomedical image datasets. The proposed
      method significantly outperforms several competing state-of-the-art methods in
      terms of classification accuracy.

PMID- 29567485
TI  - Attachment quality of children with ID and its link to maternal sensitivity and
      structuring.
AB  - BACKGROUND: Attachment theory produced a fertile field of research and clinical
      application. Although the topic of attachment of children with intellectual
      disability (ID) has received increasing research attention over the past 15
      years, the empirical evidence is still limited. AIMS: We applied theoretical and
      empirical knowledge of parenting typically developing children to examine the
      mother-child relationship in the ID population. The aim was to examine maternal
      sensitivity and structuring and its association with children's attachment
      classification and their disability. METHODS: Forty preschool children (mean age
      47.25, range 26-75 months) with non-specific ID and their mothers participated in
      the study. The mean developmental age was 25.92 months (SD = 10.89), The DQ mean
      score was 55.45 (SD = 17.28). We assessed children's quality of attachment using
      the SSP and maternal interactive behavior using the Emotional Availability
      Scales. OUTCOMES: Forty percent of children showed secure attachment, and 32.5%
      showed disorganized attachment. Attachment classifications correlated
      significantly with maternal sensitivity and maternal structuring but not with the
      child's cognitive disability. CONCLUSIONS: The results point to the importance of
      maternal interactive behavior for children with ID. Clinical implication may
      consider interventions aiming to enhance maternal sensitivity and structuring to
      improve children's quality of attachment.

PMID- 29567486
TI  - Genetic Evaluation of Cardiomyopathy-A Heart Failure Society of America Practice
      Guideline.
AB  - This guideline describes the approach and expertise needed for the genetic
      evaluation of cardiomyopathy. First published in 2009 by the Heart Failure
      Society of America (HFSA), the guideline has now been updated in collaboration
      with the American College of Medical Genetics and Genomics (ACMG). The writing
      group, composed of cardiologists and genetics professionals with expertise in
      adult and pediatric cardiomyopathy, reflects the emergence and increased clinical
      activity devoted to cardiovascular genetic medicine. The genetic evaluation of
      cardiomyopathy is a rapidly emerging key clinical priority, because high
      throughput sequencing is now feasible for clinical testing and conventional
      interventions can improve survival, reduce morbidity, and enhance quality of
      life. Moreover, specific interventions may be guided by genetic analysis. A
      systematic approach is recommended: always a comprehensive family history; an
      expert phenotypic evaluation of the proband and at-risk family members to confirm
      a diagnosis and guide genetic test selection and interpretation; referral to
      expert centers as needed; genetic testing, with pre- and post-test genetic
      counseling; and specific guidance as indicated for drug and device therapies. The
      evaluation of infants and children demands special expertise. The approach to
      managing secondary and incidental sequence findings as recommended by the ACMG is
      provided.

PMID- 29567487
TI  - Two new species of Gyrodactylus von Nordmann, 1832 from Profundulus oaxacae
      (Pisces: Profundulidae) from Oaxaca, Mexico, studied by morphology and molecular
      analyses.
AB  - In the present study, two new species of Gyrodactylus are described from
      Profundulus oaxacae, a fish endemic to the Pacific slope of Oaxaca State, Mexico.
      Fishes were collected within their distribution range in 5 localities in the
      Atoyac-Verde River. Gyrodactylus montealbani n. sp. and G. zapoteco n. sp. were
      erected and characterized morphologically (sclerites of the attachment apparatus
      and the male copulatory organ) and molecularly (sequences of the Internal
      Transcribed Spacer region of rDNA). The haptoral sclerites of the new species are
      similar to those of Gyrodactylus iunuri and Gyrodactylus tepari, both recently
      described from the goodeid fish Goodea atripinnis, from the Mexican States of
      Jalisco and Queretaro, respectively; and to Gyrodactylus xtachuna described from
      the poeciliid Poeciliopsis gracilis in Veracruz State, Mexico - nonetheless,
      these species can all be discriminated based on their marginal hook morphology.
      Specimens of G. montealbani n. sp. and G. zapoteco n. sp. were sequenced, and
      were aligned with sequences of 25 other Gyrodactylus spp. Both Maximum likelihood
      and Bayesian inference analyses indicated that the two new species are members of
      independent, well-supported lineages - these are the first Gyrodactylus species
      described from Profundulus oaxacae.

PMID- 29567488
TI  - Blockade of nuclear factor-kappaB (NF-kappaB) pathway inhibits growth and induces
      apoptosis in chemoresistant ovarian carcinoma cells.
AB  - Epithelial ovarian cancer (EOC) has exhibited marginal improvement in survival
      rate, despite advances in surgical debulking and chemotherapy regimens. Although
      the majority of EOC patients achieve a clinical remission after induction
      therapy, over 80% relapse and succumb to chemoresistant disease. In this regard,
      it is of paramount importance to elucidate molecular mechanisms and signaling
      pathways which promote therapy resistance in EOC in order to devise novel and
      more effective treatment strategies. In this study, we showed that activation of
      nuclear factor-kappaB (NF-kappaB) is significantly higher in therapy-resistant
      EOC cells compared to chemosensitive counterparts, which was positively
      associated with resistance to cisplatin, carboplatin, paclitaxel and erlotinib.
      Bay 11-7082, a highly selective NF-kappaB inhibitor, reduced cell proliferation,
      clonogenicity and anoikis resistance in the therapy-resistant EOC cells and
      induced apoptotic cell death. Moreover, Bay 11-7082 decreased the expression of
      pro-survival, inflammatory and metastatic genes and synergistically increased
      anti-proliferative efficacy of cisplatin, carboplatin, paclitaxel and erlotinib.
      Altogether, these findings suggest that NF-kappaB is an attractive therapeutic
      target in EOC to be exploited in translational oncology and Bay 11-7082 is a
      potential anti-cancer drug to overcome chemoresistance and inhibit proliferation
      of the EOC cells.

PMID- 29567489
TI  - QM/MM analysis of effect of divalent metal ions on OPRT action.
AB  - The role of Mg2+ cofactor in orotate phosphoribosyltransferase (OPRT) catalyzed
      synthesis of orotidine monophosphate (OMP) from phosphoribosyl pyrophosphate
      (PRPP) and orotate (OA) in substrate binding and the influence of the identity of
      the divalent metal ion on the reaction mechanism were addressed in this study
      using quantum mechanics/molecular mechanics framework. Energetics of migration
      and binding of different substrate complexes in the active site cavity was
      established. A quantitative analysis of various processes indicated the reaction
      pathway to consist of complexation of Mg2+ with PRPP, migration of Mg2+-PRPP and
      OA towards the active site, binding of OA to OPRT, and binding of Mg2+-PRPP
      complex to OA-OPRT complex. The mechanism of the reaction was unaltered by the
      change in the identity of divalent metal ion. Experimentally reported inhibiting
      character of Co2+ was explained on the basis of large Co2+-PRPP binding and
      migration energies. Mg2+, Ca2+, Mn2+, Co2+ and Zn2+ ions were screened
      computationally to assess their inhibiting/activating characteristics. Trends
      obtained by our computational investigations were in correspondence with
      experimentally reported trends.

PMID- 29567490
TI  - Temperature effect on the structure and conformational fluctuations in two zinc
      knuckles from the mouse mammary tumor virus.
AB  - Zinc fingers are small protein domains in which zinc plays a structural role,
      contributing to the stability of the zinc-peptide complex. Zinc fingers are
      structurally diverse and are present in proteins that perform a broad range of
      functions in various cellular processes, such as replication and repair,
      transcription and translation, metabolism and signaling, cell proliferation, and
      apoptosis. Zinc fingers typically function as interaction modules and bind to a
      wide variety of compounds, such as nucleic acids, proteins, and small molecules.
      In this study, we investigated the structural properties, in solution, of the
      proximal and distal zinc knuckles of the nucleocapsid (NC) protein from the mouse
      mammary tumor virus (MMTV) (MMTV NC). For this purpose, we performed a series of
      molecular dynamics simulations in aqueous solution at 300 K, 333 K, and 348 K.
      The temperature effect was evaluated in terms of root mean square deviation of
      the backbone atoms and root mean square fluctuation of the coordinating residue
      atoms. The stability of the zinc coordination sphere was analyzed based upon the
      time profile of the interatomic distances between the zinc ions and the chelator
      atoms. The results indicate that the hydrophobic character of the proximal zinc
      finger is dominant at 333 K. The low mobility of the coordinating residues
      suggests that the strong electrostatic effect exerted by the zinc ion on its
      coordinating residues is not influenced by the increase in temperature. The
      evolution of the structural parameters of the coordination sphere of the distal
      zinc finger at 300 K gives us a reasonable picture of the unfolding pathway, as
      proposed by Bombarda and coworkers (Bombarda et al., 2005), which can predict the
      binding order of the four conserved ligand-binding residues. Our results support
      the conclusion that the structural features can vary significantly between the
      two zinc knuckles of MMTV NC.

PMID- 29567491
TI  - Adolescent psychopathology in Times of Change: The need for integrating a
      developmental psychopathology perspective.
AB  - In addition to the major physical, sexual and cognitive changes, as well as
      changes in relationships with parents and peers, in recent years adolescents also
      have to cope with many technological changes and increasing societal
      instabilities. Most of the existing research has examined the extent to which
      increasing uncertainties might impact expression of psychopathology and its
      magnitude. Emerging from a developmental psychopathology perspective, we are
      looking first for a better understanding of the meaning that adolescents give to
      these changes, which in turn is likely to affect their behavior. We are also
      looking for better understanding the importance of the role parents, and other
      societal systems/institutions (such as peers) play in ameliorating or enhancing
      the likelihood of maladaptive adolescent behavior under these circumstances.

PMID- 29567492
TI  - Paternal Cocaine Disrupts Offspring Circadian Clock Function in a Sex-Dependent
      Manner in Mice.
AB  - The present study is the first to explore the multigenerational effects of
      mammalian paternal cocaine intake on offspring (F1) circadian clock regulation.
      Parental cocaine use poses significant health risks to the offspring, through
      both maternal and paternal drug influences. With respect to the latter, recent
      evidence suggests that a paternal mode of cocaine inheritance involves epigenetic
      germ line actions that can ultimately disrupt offspring behavior. Based on our
      previous report in mice that free-running circadian period (tau) is chronically
      lengthened following withdrawal from long-term cocaine treatment, the present
      study was undertaken to explore potential epigenetic effects of paternal exposure
      to cocaine over the ~40-day murine spermatogenic cycle on F1 circadian regulatory
      functions. Here we show that, although withdrawal of sires from the cocaine
      treatment lengthened their tau, such an effect did not persist in adult F1 male
      or female offspring born from drug-naive dams. Notably, however, there was a
      distinct deficit in the ability of F1 cocaine-sired males, but not females, to
      undergo light-induced phase delay shifts of the circadian clock. In contrast, F1
      cocaine-sired females, but not males, had suppressed circadian phase advance
      shifting responses to two non-photic stimuli: acute i.p. injections of cocaine
      and the serotonin agonist ([+]8-OH-DPAT). The reduced cocaine shifting in females
      was not due to suppressed cocaine-induced behavioral arousal. Collectively, these
      results reveal that a father's cocaine use can disrupt major circadian
      entrainment mechanisms in his adult progeny in a sex-dependent manner.

PMID- 29567493
TI  - It is not just the number of metaphases that matters.

PMID- 29567494
TI  - Peptide recognition, signaling and modulation of class B G protein-coupled
      receptors.
AB  - Class B G protein-coupled receptors (GPCRs) are important drug targets in many
      human diseases, including type 2 diabetes, obesity, cardiovascular disease and
      neurodegeneration. Peptide hormones bind to these receptors through interactions
      with both the extracellular domain and transmembrane domain. Despite remarkable
      advances in structural studies of GPCRs, structural characterization of the full
      length class B receptors remains extremely challenging due to their
      conformational complexity. The recently solved structures of class B GPCRs reveal
      the structural basis of peptide ligand recognition and modulation mechanisms of
      small molecule allosteric modulators. Furthermore, these structures provide
      essential insights into molecular mechanisms of class B GPCR signal transduction
      and modulation.

PMID- 29567495
TI  - Characterizing exposure to household air pollution within the Prospective Urban
      Rural Epidemiology (PURE) study.
AB  - BACKGROUND: Household air pollution (HAP) from combustion of solid fuels is an
      important contributor to disease burden in low- and middle-income countries (LIC,
      and MIC). However, current HAP disease burden estimates are based on integrated
      exposure response curves that are not currently informed by quantitative HAP
      studies in LIC and MIC. While there is adequate evidence supporting causal
      relationships between HAP and respiratory disease, large cohort studies
      specifically examining relationships between quantitative measures of HAP
      exposure with cardiovascular disease are lacking. OBJECTIVE: We aim to improve
      upon exposure proxies based on fuel type, and to reduce exposure
      misclassification by quantitatively measuring exposure across varying cooking
      fuel types and conditions in diverse geographies and socioeconomic settings. We
      leverage technology advancements to estimate household and personal PM2.5
      (particles below 2.5 MUm in aerodynamic diameter) exposure within the large
      (N~250,000) multi-country (N~26) Prospective Urban and Rural Epidemiological
      (PURE) cohort study. Here, we detail the study protocol and the innovative
      methodologies being used to characterize HAP exposures, and their application in
      epidemiologic analyses. METHODS/DESIGN: This study characterizes HAP PM2.5
      exposures for participants in rural communities in ten PURE countries with >10%
      solid fuel use at baseline (Bangladesh, Brazil, Chile, China, Colombia, India,
      Pakistan, South Africa, Tanzania, and Zimbabwe). PM2.5 monitoring includes 48-h
      cooking area measurements in 4500 households and simultaneous personal monitoring
      of male and female pairs from 20% of the selected households. Repeat measurements
      occur in 20% of households to assess impacts of seasonality. Monitoring began in
      2017, and will continue through 2019. The Ultrasonic Personal Aerosol Sampler
      (UPAS), a novel, robust, and inexpensive filter based monitor that is
      programmable through a dedicated mobile phone application is used for sampling.
      Pilot study field evaluation of cooking area measurements indicated high
      correlation between the UPAS and reference Harvard Impactors (r = 0.91; 95% CI:
      0.84, 0.95; slope = 0.95). To facilitate tracking and to minimize contamination
      and analytical error, the samplers utilize barcoded filters and filter cartridges
      that are weighed pre- and post-sampling using a fully automated weighing system.
      Pump flow and pressure measurements, temperature and RH, GPS coordinates and semi
      quantitative continuous particle mass concentrations based on filter differential
      pressure are uploaded to a central server automatically whenever the mobile phone
      is connected to the internet, with sampled data automatically screened for
      quality control parameters. A short survey is administered during the 48-h
      monitoring period. Post-weighed filters are further analyzed to estimate black
      carbon concentrations through a semi-automated, rapid, cost-effective image
      analysis approach. The measured PM2.5 data will then be combined with PURE survey
      information on household characteristics and behaviours collected at baseline and
      during follow-up to develop quantitative HAP models for PM2.5 exposures for all
      rural PURE participants (~50,000) and across different cooking fuel types within
      the 10 index countries. Both the measured (in the subset) and the modelled
      exposures will be used in separate longitudinal epidemiologic analyses to assess
      associations with cardiopulmonary mortality, and disease incidence. DISCUSSION:
      The collected data and resulting characterization of cooking area and personal
      PM2.5 exposures in multiple rural communities from 10 countries will better
      inform exposure assessment as well as future epidemiologic analyses assessing the
      relationships between quantitative estimates of chronic HAP exposure with adult
      mortality and incident cardiovascular and respiratory disease. This will provide
      refined and more accurate exposure estimates in global CVD related exposure
      response analyses.

PMID- 29567496
TI  - Immobilization of laccase on modified Fe3O4@SiO2@Kit-6 magnetite nanoparticles
      for enhanced delignification of olive pomace bio-waste.
AB  - Lignocellulose is considered a major source for the production of valuable
      chemicals. Efficient degradation of lignin as the natural carrier of the
      lignocellulosic biomass represents a key limiting factor in biomass
      digestibility. Recently, biological delignification methods have been promoted as
      sustainable and environmentally friendly alternatives to the traditional
      technologies. In this study, porous nanocomposite of Fe3O4@SiO2@KIT-6 with
      magnetic properties was synthesized. The immobilized laccase supported on
      nanocomposite with enhanced stability in a hydrophobic ionic liquid has been
      developed for both olive pomace delignification and degradation of phenolic
      extracts from the pomace. After 6h incubation, the degradation rate of lignin and
      phenol by the immobilized laccase was estimated to be 77.3% and 76.5%,
      respectively. The immobilized laccase retained 70% of its initial degradation
      ability after 11 successive batch treatments of olive pomace. Furthermore, the
      immobilized laccase retained >70% of its initial activity after 21days of storage
      at room temperature. The obtained results indicated that the immobilized laccase
      on magnetic mesoporous support together with (1-Butyl-3-methylimidazolium
      hexafluorophosphate) ([Bmim][PF6]) could potentially provide a promising
      procedure for an improved enzymatic degradation of lignin and phenol in the
      related industries.

PMID- 29567497
TI  - Biocatalytic action of proteases in ionic liquids: Improvements on their
      enzymatic activity, thermal stability and kinetic parameters.
AB  - This study evaluated the effect of the addition of the following ionic liquids
      (IL): choline chloride (CC), tetramethylammonium bromide (TB) and 1-ethyl-3
      methylimidazolium bromide (EM), on some biochemical properties including
      enzymatic activity and different kinetic parameters of commercial proteases. The
      enzyme-IL combinations that showed the highest increases in enzyme activities
      were as follows: CC (0.5mM) and Neutrase(r) 0.8L; CC (5mM) and Flavourzyme(r)
      500L; TB (2000mM) and Alcalase(r) 2.4L, with relative increases of 20, 15 and
      150% in protease activities, respectively, compared to the control assays. The
      combination TB and Alcalase(r) 2.4L showed a reduction of 50% of the activation
      energy (Ea), an increase of the relation Vmax/Km of 35% and a 16-fold rise in the
      values of t1/2, and D. Neutrase(r) 0.8L combined with CC showed an increase of
      20% in the relation Vmax/Km. The combination Flavourzyme(r) 500L and CC presented
      a 20% higher value of the relation Vmax/Km and a 2-fold increase in the values of
      t1/2 and D compared to the control assay. In summary, the most positive effects
      observed in this study included proteases with improved activity and stability
      properties and a greater affinity for the substrate.

PMID- 29567498
TI  - Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended
      release of diclofenac sodium using 32 full factorial design.
AB  - Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h
      Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 32
      full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG
      and TSG and concentration of cross-linker CaCl2 were taken as independent factors
      with three different levels of each. Effects of polymer ratio and CaCl2 on drug
      entrapment efficiency (DEE), drug release, bead size and swelling were
      investigated. Responses such as DEE and different drug release parameters were
      statistically analyzed by 32 full factorial design using Design-Expert software
      and finally the formulation factors were optimized to obtain USP-reference
      release profile. Drug release rate was found to decrease with decrease in the
      ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca2+ ions in cross
      linking medium. The optimized formulation showed DEE of 93.25% and an extended
      drug release profile over a period of 10h with f2=80.13. Kinetic modeling
      unveiled case-I-Fickian diffusion based drug release mechanism.

PMID- 29567499
TI  - Redox responsive curcumin-loaded human serum albumin nanoparticles: Preparation,
      characterization and in vitro evaluation.
AB  - The purpose of this study was to fabricate redox-responsive human serum albumin
      (HSA) nanoparticles (NPs) through self-assembly of HSA molecules for
      incorporation of curcumin (CCM) as a hydrophobic drug molecule. The structural
      changes of HSA in self-assembly process of nanoparticle formation were
      investigated using fluorescence, UV-vis, circular dichroism spectroscopy and X
      ray diffraction. Spectroscopy data show changes in secondary and tertiary
      structures of HSA in the process of nanoparticle formation, which can be
      indicative of the interaction of the hydrophobic drug with HSA molecules. Unlike
      free CCM, nanoparticulate curcumin is readily dispersed in aqueous medium.
      Furthermore, self-assembled HSA-CCM NPs release CCM in an environment imitating
      the intracellular environment with the trigger of acidic pH and redox potential.
      The in vitro release studies showed that at pH7.4 only 26% CCM was released from
      CCM-loaded HSA NPs in 48h. However, the release of CCM was significantly
      accelerated in the presence of 10mM glutathione (GSH) at pH7.4 or pH5.5, in which
      57% and 70% of CCM was released, respectively. The incorporation of CCM in HSA
      nanoparticles enhanced the cellular uptake of CCM in comparison with free CCM
      results in higher anticancer efficacy against MCF-7 cells.

PMID- 29567500
TI  - Enhanced activity and stability of papain by covalent immobilization on porous
      magnetic nanoparticles.
AB  - Papain enzyme was successfully immobilized by covalent bonding onto biocompatible
      Fe3O4/SF nanoparticles, which were prepared with the soft template of silk
      fibroin (SF). The optimized immobilization condition is pH6.0, hydrolysis time of
      60min, and an enzyme/support ratio of 10.0mg/g. Compared with free papain, the
      immobilized papain exhibits a high effective activity, broader working pH and
      temperature. This immobilized papain can be separated from the solution by the
      external magnetic field for cyclic utilization, and 70% of initial activity was
      retained after eight consecutive operations while completely loss of proteolytic
      activity for the free papain. Furthermore, the immobilized papain maintained 85%
      of their initial activity after being stored for 28days. Kinetic parameters,
      maximum reaction rate (Vmax) and Michaelis constant (Km) of immobilized papain,
      were determined as 4.95mg/l.min and 0.23mg/ml, larger than its free counterpart.
      All the results above indicated that the immobilized papain onto magnetic
      Fe3O4/SF nanoparticles would have potential industrial and medical applications.

PMID- 29567501
TI  - The role of probiotic Lactobacillus acidophilus ATCC 4356 bacteriocin on effect
      of HBsu on planktonic cells and biofilm formation of Bacillus subtilis.
AB  - : Bacillus subtilis is a Gram positive, aerobic and motile bacterium. Biofilm
      formation is an important feature of this bacterium which confers resistance to
      antimicrobial agents. The use of new antimicrobial reagents which eliminate
      biofilms are important and necessary. In this study, the effect of secondary
      metabolites (bacteriocin) from Lactobacillus acidophilus ATCC 4356 on Bacillus
      subtilis BM19 in the presence and absence of HBsu which is involved in the growth
      of planktonic cells and biofilm formation, is reported. HBsu nucleoprotein plays
      several roles in different processes of Bacillus subtilis cells such as
      replication, transcription, cell division, recombination and repair. In this
      study, for the first time, the effect of HBsu on biofilm formation is presented.
      RESULTS: In the absence of HBsu, purified bacteriocin from L. acidophilus ATCC
      4356 was more effective in inhibiting growth of B. subtilis BM19 planktonic cells
      as well as biofilm formation. The presence of HBsu on the other hand led to
      increased biofilm formation.

PMID- 29567502
TI  - Early cross-modal interactions underlie the audiovisual bounce-inducing effect.
AB  - Two identical visual disks moving towards one another on a two-dimensional
      display can be perceived as either "streaming through" or "bouncing off" each
      other after their coincidence/overlapping. A brief sound presented at the moment
      of the coincidence of the disks could strikingly bias the percept towards
      bouncing, which was termed the audiovisual bounce-inducing effect (ABE). Although
      the ABE has been studied intensively since its discovery, the debate about its
      origin is still unresolved so far. The present study used event-related potential
      (ERP) recordings to investigate whether or not early neural activities associated
      with cross-modal interactions play a role on the ABE. The results showed that the
      fronto-central P2 component ~200 ms before the coincidence of the disks was
      predictive of subsequent streaming or bouncing percept in the unimodal visual
      display but not in auditory-visual display. More importantly, the cross-modal
      interactions revealed by the fronto-central positivity PD170 (125-175 ms after
      sound onset), as well as the occipital positivity PD190 (180-200 ms), were
      substantially enhanced on bouncing trials compared to streaming trials in the
      auditory-visual display. These findings provide direct electrophysiological
      evidence that early cross-modal interactions contribute to the origin of ABE
      phenomenon at the perceptual stage of processing.

PMID- 29567503
TI  - Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio
      in the cerebral cortex.
AB  - Magnetic resonance (MR) images of the brain are of immense clinical and research
      utility. At the atomic and subatomic levels, the sources of MR signals are well
      understood. However, we lack a comprehensive understanding of the macromolecular
      correlates of MR signal contrast. To address this gap, we used genome-wide
      measurements to correlate gene expression with MR signal intensity across the
      cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of
      T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is
      considered to be a useful proxy for myelin content. As expected, we found
      enrichment of positive correlations between myelin-associated genes and the ratio
      image, supporting its use as a myelin marker. Genome-wide, there was an
      association with protein mass, with genes coding for heavier proteins expressed
      in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly
      correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated
      genes. Mitochondrial genes exhibit the strongest relationship, showing higher
      expression in regions with low T1-w/T2-w ratio. This may be due to the pH
      gradient in mitochondria as genes up-regulated by pH in the brain were also
      highly correlated with the ratio. While we corroborate associations with myelin
      and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are
      more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and
      pH. We evaluate correlations between AHBA transcriptomic measurements and a group
      averaged T1-w/T2-w ratio image, showing agreement with in-sample results.
      Expanding our analysis to the whole brain results in strong positive T1-w/T2-w
      correlations for immune system, inflammatory disease, and microglia marker genes.
      Genes with negative correlations were enriched for neuron markers and synaptic
      plasticity genes. Lastly, our findings are similar when performed on T1-w or
      inverted T2-w intensities alone. These results provide a molecular
      characterization of MR contrast that will aid interpretation of future MR studies
      of the brain.

PMID- 29567505
TI  - The effect of missing data on coalescent species delimitation and a taxonomic
      revision of whipsnakes (Colubridae: Masticophis).
AB  - A stable alpha taxonomy is essential to understanding evolutionary processes and
      achieving effective conservation aims. Taxonomy depends on the identification of
      independently evolving lineages, and the delimitation of these lineages based on
      multiple lines of evidence. Coalescent species delimitation within an integrative
      framework has increased the rigor of the delimitation process. Here we use genome
      wide SNP data and coalescent species delimitation to explore lineage
      relationships within several North American whipsnake species, test the species
      status of several lineages, and test the effect of missing data on species
      delimitation. We find support for the elevation of several previously recognized
      subspecies to full species status, and formally elevate two species. This study
      demonstrates the power of molecular data and model-based delimitation methods to
      identify evolutionary relationships, and finds that missing data have little
      impact on the outcome of delimitation analyses.

PMID- 29567504
TI  - Age-related changes in cerebrovascular reactivity and their relationship to
      cognition: A four-year longitudinal study.
AB  - Although cerebrovascular factors are the second leading cause of cognitive
      impairment and dementia in elderly, the precise spatial and temporal trajectories
      of vascular decline in aging have not been fully characterized. With an advanced
      cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular
      stiffness and dilatory ability of cerebral vessels, we present four-year
      longitudinal CVR data measured in 116 healthy individuals (20-88 years of age).
      Our data revealed a spatial heterogeneity in vascular decline in aging (p =
      0.003), in that temporal lobe showed the fastest rate of longitudinal CVR
      decline, followed by parietal and frontal lobes. The rate of CVR decline was also
      age-dependent. Middle age, not older age, manifested the fastest rate of
      longitudinal CVR decline (p < 0.05). Longitudinal changes in CVR were associated
      with changes in processing speed (p = 0.031) and episodic memory (p = 0.022), but
      not with working memory or reasoning. The rate of longitudinal CVR change was not
      different between hypertensive and normotensive participants. However, cross
      sectionally, individuals with hypertension revealed in a lower CVR compared to
      normotensive participants (p = 0.016). These findings help elucidate age-related
      decline in brain hemodynamics and support CVR as a non-invasive biomarker in
      evaluating cerebrovascular conditions in elderly individuals.

PMID- 29567506
TI  - Phylogeny of the subfamily Stelliferinae suggests speciation in Ophioscion Gill,
      1863 (Sciaenidae: Perciformes) in the western South Atlantic.
AB  - Phylogenies based on morphological and molecular data confirm the monophyly of
      the subfamily Stelliferinae; however, there is no consensus on the intergeneric
      and interspecific relationships in the group. Previous studies suggested the non
      monophyly of Ophioscion and Stellifer, and possible cryptic species in Ophioscion
      punctatissimus. Therefore, we used mitochondrial (16S rDNA and COI) and nuclear
      (Rhodopsin, EGR1, and RAG1) regions to examine phylogenetic relationships among
      species of this subfamily. Our results confirmed the monophyly of Stelliferinae
      and supports the close relationship among Bardiella, Corvula and Odontoscion,
      which form a sister group to Stellifer and Ophioscion. Notwithstanding, all the
      results support the non-monophyly of Stellifer and Ophioscion and we suggest that
      a taxonomic revision should consider Ophioscion as a junior synonym of Stellifer.
      Moreover, O. punctatissimus was grouped into two clades, with the O.
      punctatissimus lineage I (LI) being closer to O. scierus from the eastern Pacific
      than to the O. punctatissimus lineage II (LII). The most recent common ancestor
      (TMRCA) for the O. scierus and O. punctatissimus LI and O. punctatissimus LII
      clade dates from 7.2 (HPD: 4.3-10.5) Ma, whereas TMRCA for the O. scierus and O.
      punctatissimus LI clade dates from 5.3 (HPD: 2.4-8.6) Ma, indicating that
      speciation processes may be related to the rise of the Isthmus of Panama.
      Phylogeographic analyses corroborate the hypothesis of speciation in O.
      punctatissimus. These results suggest that lineages of O. punctatissimus
      originated from distinct ancestors and, by morphological similarity, were
      considered the same taxon. A taxonomic revision should be performed to validate
      the species status of such lineages.

PMID- 29567507
TI  - Acceptability of latent tuberculosis testing of migrants in a college environment
      in England.
AB  - OBJECTIVES: The majority of tuberculosis (TB) cases in England occur from
      reactivation of latent tuberculosis infection (LTBI) in the settled migrant
      population. The National Institute for Health and Clinical Excellence recommends
      that new entrants from high-incidence countries are screened to detect LTBI. This
      article seeks to describe an outreach programme and testing for LTBI in an
      innovative setting-ESOL (English for Speakers of Other Languages) classes at a
      community college (CC) with evaluation of acceptability. STUDY DESIGN:
      Partnership working with mixed methods used for evaluation of acceptability.
      METHODS: A pre-existing network from the local TB partnership designed an
      outreach intervention and screening for LTBI among students from an ESOL
      programme at a CC. Screening for LTBI with interferon gamma release assay was the
      culmination of a programme of health improvement activities across the college.
      Any student on the ESOL programme younger than the age of 35 years and resident
      in the UK for less than 5 years was eligible for testing. LTBI testing was
      carried out on-site, and the experience was evaluated by questionnaires to staff,
      students and partners. A facilitated debrief among the partners gave further
      data. RESULTS: A total of 440 eligible students were tested. One hundred and
      seventy-two student feedback questionnaires were completed, and 36 partner
      questionnaires were received with 18 CC staff responding. Students, tutors and
      healthcare professionals found the setting acceptable with some concerns about
      insufficient resource for timely follow-up. CONCLUSIONS: Students, tutors,
      community organisations and health professionals found the exercise worthwhile
      and the method and setting acceptable. There were resource issues for the
      clinical team in follow-up of students with positive results for such a large
      screening event. Unexpected barriers were found by the CC as this kind of
      activity was not recognised for external quality review purposes. There were
      concerns about reputational loss and stigma of being involved in a TB project. As
      current initiatives aim to divert workload from stretched general practice
      surgeries, this may be an important addition to primary care screening.

PMID- 29567508
TI  - Ectopic expression of SaNRAMP3 from Sedum alfredii enhanced cadmium root-to-shoot
      transport in Brassica juncea.
AB  - SaNRAMP3 gene cloned from a Zn/Cd hyperaccumulator Sedum alfredii was ectopicly
      expressed in Brassica juncea, a fast-growing and high-biomass crop plant. In a
      tissue culture experiment, transgenic plants were grown on MS medium with 0, 25,
      50, 100, 200 MUM Cd. It was shown that, at the same Cd treatment, the Cd
      tolerance of transgenic plants had no significant difference with those of wild
      type plants (WT). However, the shoot Cd content and accumulation were improved
      significantly while the root Cd content and accumulation were descended
      significantly by SaNRAMP3 gene expression, which obviously enhanced the Cd root
      to-shoot translocation factor (TF). In the hydroponic experiment, plants were
      cultured in nutrition solution with 0, 2.5, 25 MUM Cd. Data showed that the Cd
      tolerance of transgenic plants had no significant difference with that of WT
      under the same Cd exposure. Whereas, the shoot Cd content and accumulation was
      increased 1.43-1.81 times and the TF was enhanced 3.09-3.51 times by SaNRAMP3
      gene expression. Those results indicated that ectopic expression of SaNRAMP3 in
      B. juncea didn't lead to Cd sensitivity, but enhanced Cd root-to-shoot transport,
      so that increased shoot Cd accumulation. This study provided a possibility to
      improve phytoextraction efficiency of heavy metal through gene engineering.

PMID- 29567509
TI  - Effect of graphene oxide on the bioactivities of nitrifying and denitrifying
      bacteria in aerobic granular sludge.
AB  - With the widespread application of graphene oxide (GO), it would be inevitably
      released into wastewater treatment plants (WWTPs) and get involved in the
      biochemical process. So far, there are controversies on the effects of low GO
      concentration (0.05-0.1 g/L) on the nitrogen removal process. Therefore, this
      study essentially investigates any potential effects of GO on wastewater
      microbial communities functions. In present study, the nitrifying and
      denitrifying batch tests were introduced to investigate the influence of 0.06 g/L
      of GO on bacteria. The results showed that GO could be easily combined with the
      aerobic granular sludge (AGS), and NH4+-N was sharply absorbed, which directly
      promoted the bioactivities of ammonium oxidizing bacteria (AOB) and nitrite
      oxidizing bacteria (NOB) and extracellular polymeric substances (EPS) production.
      The influence of GO on the denitrifying bacteria was negligible, which resulted
      in the stable EPS production. Furthermore, as inferred from the near maximum
      chemical reaction rates, there were no obvious changes on the microbial community
      functions during nitrogen removal process.

PMID- 29567511
TI  - The transition from HLA-I positive to HLA-I negative primary tumors: the road to
      escape from T-cell responses.
AB  - MHC/HLA class I loss in cancer is one of the main mechanisms of tumor immune
      escape from T-cell recognition and destruction. Tumor infiltration by T
      lymphocytes (TILs) and by other immune cells was first described many years ago,
      but has never been directly and clearly linked to the destruction of HLA-I
      positive and selection of HLA-I negative tumor cells. The degree and the pattern
      of lymphocyte infiltration in a tumor nest may depend on antigenicity and the
      developmental stages of the tumors. In addition, it is becoming evident that HLA
      I expression and tumor infiltration have a direct correlation with tumor tissue
      reorganization. We observed that at early stages (permissive Phase I) tumors are
      heterogeneous, with both HLA-I positive and HLA-negative cancer cells, and are
      infiltrated by TILs and M1 macrophages as a part of an active anti-tumor Th1
      response. At later stages (encapsulated Phase II), tumor nests are mostly HLA-I
      negative with immune cells residing in the peri-tumoral stroma, which forms a
      granuloma-like encapsulated tissue structure. All these tumor characteristics,
      including tumor HLA-I expression pattern, have an important clinical prognostic
      value and should be closely and routinely investigated in different types of
      cancer by immunologists and by pathologists. In this review we summarize our
      current viewpoint about the alterations in HLA-I expression in cancer and discuss
      how, when and why tumor HLA-I losses occur. We also provide evidence for the
      negative impact of tumor HLA-I loss in current cancer immunotherapies, with the
      focus on reversible ('soft') and irreversible ('hard') HLA-I defects.

PMID- 29567512
TI  - The effects of one night of partial sleep deprivation on executive functions in
      individuals reporting chronic insomnia and good sleepers.
AB  - BACKGROUND AND OBJECTIVES: The aim of the present study was to investigate the
      effects of a partial sleep deprivation night on executive functions in
      participants reporting chronic insomnia and good sleepers using a Task Switching
      paradigm. METHODS: Sixteen participants reporting symptoms of chronic insomnia
      and sixteen good sleepers were tested after a night of habitual sleep and after a
      night of partial sleep deprivation (5 h of sleep allowed). The Switch Cost (SC)
      and the Backward Inhibition (BI) were computed as measures of switching attention
      and response inhibition, respectively. RESULTS: We observed a marginally
      significant interaction Night * Group on SC (F(1,29) = 4.06, p = 0.053), eta2 =
      0.123. Fisher's least significant difference (LSD) post-hoc revealed a smaller SC
      after the sleep deprived night relative to the habitual night for the good
      sleepers (p = 0.027; M = 192.23 +/- 201.81 vs M = 98.99 +/- 141.16). Differently,
      participants with insomnia did not show any change after the two nights.
      LIMITATIONS: Several limitations must be acknowledged including the use of a
      convenient sample of university students and the use of a single task of
      cognitive performance. CONCLUSIONS: We found that SC was smaller in the good
      sleepers after a night of partial sleep deprivation compared to a habitual night,
      indicating a better switching performance. The insomnia group showed no
      differences in performance after the two experimental nights. Several factors may
      account for these results, including increased levels of arousal and cognitive
      effort during task execution.

PMID- 29567513
TI  - Aestivalosides A-L, twelve pregnane glycosides from the seeds of Adonis
      aestivalis.
AB  - Eight adonilide (14,20alpha-epoxy-3beta,20-dihydroxy-14beta-pregn-5-en-18-oic
      acid gamma-lactone) glycosides, named aestivalosides A-H, and four glycosides of
      the adonilide derivatives, named aestivalosides I-L, were isolated from the MeOH
      extract of seeds of Adonis aestivalis. Aestivalosides A-L were previously
      undescribed compounds, and were structurally characterized using spectroscopic
      techniques, including two-dimensional NMR, and chemical methods.

PMID- 29567510
TI  - The effects of early life stress on reward processing.
AB  - Early life stress (ELS), in the form of childhood maltreatment, abuse, or
      neglect, increases the risk for psychiatric sequelae later in life. The
      neurobiology of response to early stress and of reward processing overlap
      substantially, leading to the prediction that reward processing may be a primary
      mediator of the effects of early life stress. We describe a growing body of
      literature investigating the effects of early life stressors on reward processing
      in animals and humans. Despite variation in the reviewed studies, an emerging
      pattern of results indicates that ELS results in deficits of ventral striatum
      related functions of reward responsiveness and approach motivation, especially
      when the stressor is experienced in early in development. For stressors
      experienced later in the juvenile period and adolescence, the animal literature
      suggests an opposite effect, in which ELS results in increased hedonic drive.
      Future research in this area will help elucidate the transdiagnostic impact of
      early life stress, and therefore potentially identify and intervene with at-risk
      youth, prior to the emergence of clinical psychopathology.

PMID- 29567514
TI  - Development of an anti-dengue NS1 IgG ELISA to evaluate exposure to dengue virus.
AB  - Dengue virus infection elicits immune responses to multiple viral antigens
      including antibodies to dengue non-structural protein 1 (NS1) which are rapidly
      induced and detected within days of infection. The recombinant, live, attenuated,
      tetravalent dengue vaccine (CYD-TDV; Sanofi Pasteur) uses the yellow fever
      vaccine virus as a back-bone but expresses dengue virus pre-membrane and envelop
      proteins. Since CYD-TDV does not express dengue NS1, we evaluated the utility of
      dengue NS1-specific IgG antibodies as biomarkers of dengue exposure in CYD-TDV
      recipients and controls. We optimized and evaluated a quantitative anti-dengue
      NS1 IgG enzyme-linked immunosorbent assay (ELISA). Parameters assessed included:
      accuracy, dilutability/linearity, precision, limit of quantitation and
      specificity. The assay specificity was further evaluated using Japanese
      Encephalitis virus, West Nile virus, Yellow Fever virus or Zika virus positive
      sera samples collected following confirmed infection or vaccination. Receiver
      operating-characteristics (ROC) curves as well as sensitivity and specificity for
      discriminating previous dengue exposure were assessed using 1250 reference
      samples. Overall, the anti-dengue NS1 IgG ELISA was able to discriminate previous
      dengue exposure from non-exposure before vaccination with CYD-TDV (ROC area under
      the curve > 0.9). Assessment of paired samples from 2511 vaccinated participants
      showed high overall agreement (93%) between pre-vaccination and post-vaccination
      dengue serostatus classification based on the anti-dengue NS1 IgG ELISA. However,
      misclassification of dengue serostatus was observed after vaccination likely due
      to a combination of asymptomatic dengue infections, assay variability and a
      modest effect of CYD-TDV on the anti-dengue NS1 IgG ELISA readout.

PMID- 29567515
TI  - In-hospital complication rate following microendoscopic versus open lumbar
      laminectomy: a propensity score-matched analysis.
AB  - BACKGROUND CONTEXT: The incidence of postoperative complications after
      microendoscopic laminectomy (MEL) has not been compared with that after open
      laminectomy in a large study, so it is not clear whether MEL is a safer
      procedure. PURPOSE: The objective of this study was to compare postoperative
      morbidity and mortality following lumbar laminectomy between patients treated
      with MEL and with open laminectomy. STUDY DESIGN: This is a retrospective cohort
      study with propensity score-matched analysis. PATIENT SAMPLE: Data of patients
      who underwent elective spinal surgery between July 2010 and March 2013 were
      extracted from the Diagnosis Procedure Combination database, a nationwide
      inpatient database in Japan. OUTCOME MEASURES: Clinical outcomes included length
      of hospital stay, occurrence of major complications (cardiac events, respiratory
      complications, pulmonary embolism, stroke, and acute renal failure), surgical
      site infection (SSI), postoperative delirium, and in-hospital death. MATERIALS
      AND METHODS: Propensity score matching was performed to adjust for measured
      confounding factors, including patient age, sex, Charlson Comorbidity Index, body
      mass index, smoking status, blood transfusion, duration of anesthesia, number of
      operated disc levels, and type of hospital and hospital volumes. The clinical
      outcomes of one-to-one propensity-matched pairs of the MEL and the open
      laminectomy groups were compared. RESULTS: Of 23,317 patients identified in the
      database, 1,536 underwent MEL (6.6%). By one-to-one propensity score matching,
      1,536 pairs were selected. The distributions of patient backgrounds were closely
      balanced between the MEL and the open laminectomy groups. An analysis of 1,536
      pairs revealed that there was a significantly lower incidence of major
      postoperative complications in those who underwent MEL (1.0% vs. 2.8% for open
      laminectomy, risk difference 1.8%, 95% confidence interval [CI] 0.9%-2.9%), SSI
      (0.5% vs. 1.6% for open laminectomy, risk difference 1.1%, 95% CI 0.4%-1.9%), and
      postoperative delirium (1.1% vs. 2.3% for open laminectomy, risk difference1.2%,
      95% CI 0.3%-2.1%). The length of hospital stay was significantly shorter in those
      treated with MEL (12 days vs. 16 days for open laminectomy, p<.001). There was no
      significant difference in in-hospital mortality between the groups. CONCLUSIONS:
      Patients who underwent MEL were significantly less likely to experience major
      postoperative complications and were less likely to develop SSI and postoperative
      delirium than those who underwent open laminectomy.

PMID- 29567516
TI  - Predicting survival for metastatic spine disease: a comparison of nine scoring
      systems.
AB  - BACKGROUND CONTEXT: Despite advances in spinal oncology, research in patient
      based prognostic calculators for metastatic spine disease is lacking. Much of the
      literature in this area investigates the general predictive accuracy of scoring
      systems in heterogeneous populations, with few studies considering the accuracy
      of scoring systems based on patient specifics such as type of primary tumor.
      PURPOSE: The aim of the present study was to compare the ability of widespread
      scoring systems to estimate both overall survival at various time points and
      tumor-specific survival for patients undergoing surgical treatment for metastatic
      spine disease in order to provide surgeons with information to determine the most
      appropriate scoring system for a specific patient and timeline. STUDY DESIGN:
      This is a retrospective study. PATIENT SAMPLE: Patients who underwent surgical
      resection for metastatic spine disease at a single institution were included.
      OUTCOME MEASURES: Areas under the receiver operating characteristic curves were
      generated from comparison of actual survival of patients and survival as
      predicted by application of prevalent scoring systems. METHODS: A preoperative
      score for all 176 patients was retrospectively calculated utilizing the Skeletal
      Oncology Research Group (SORG) Classic Scoring Algorithm, SORG Nomogram, original
      Tokuhashi, revised Tokuhashi, Tomita, original Bauer, modified Bauer, Katagiri,
      and van der Linden scoring systems. Univariate and multivariate Cox proportional
      hazard models were constructed to assess the association of patient variables
      with survival. Receiver operating characteristic analysis modeling was utilized
      to quantify the accuracy of each test at different end points and for different
      primary tumor subgroups. No funds were received in support of this work. The
      authors have no conflicts of interest to disclose. RESULTS: Among all patients
      surgically treated for metastatic spine disease, the SORG Nomogram demonstrated
      the highest accuracy at predicting 30-day (area under the curve [AUC] 0.81) and
      90-day (AUC 0.70) survival after surgery. The original Tokuhashi was the most
      accurate at predicting 365-day survival (AUC 0.78). Multivariate analysis
      demonstrated multiple preoperative factors strongly associated with survival
      after surgery for spinal metastasis. The accuracy of each scoring system in
      determining survival probability relative to primary tumor etiology and time
      elapsed since surgery was assessed. CONCLUSIONS: Among the nine scoring systems
      assessed, the present study determined the most accurate scoring system for short
      term (30-day), intermediate (90-day), and long-term (365-day) survival, relative
      to primary tumor etiology. The findings of the present study may be utilized by
      surgeons in a personalized effort to select the most appropriate scoring system
      for a given patient.

PMID- 29567517
TI  - Biomechanical comparative study of the stability of injectable pedicle screws
      with different lateral holes augmented with different volumes of
      polymethylmethacrylate in osteoporotic lumbar vertebrae.
AB  - BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is widely used for pedicle
      screw augmentation in osteoporosis. Until now, there had been no studies of the
      relationship between screw stability and the distribution and volume of PMMA.
      PURPOSE: The objective of this study was to analyze the relationship between
      screw stability and the distribution pattern and injected volume of PMMA. STUDY
      DESIGN: This is a biomechanical comparison of injectable pedicle screws with
      different lateral holes augmented with different volumes of PMMA in cadaveric
      osteoporotic lumbar vertebrae. METHODS: Forty-eight osteoporotic lumbar vertebrae
      were randomly divided into Groups A, B, and C with different pedicle screws (16
      vertebrae in each group), and then each group was randomly divided into Subgroups
      0, 1, 2, and 3 with different volumes of PMMA (four vertebra with eight pedicles
      in each subgroup). A pilot hole was prepared in advance using the same method in
      all samples. Type A and type B pedicle screws were directly inserted into
      vertebrae in Groups A and B, respectively, and then different volumes of PMMA (0,
      1.0, 1.5, and 2.0 mL) were injected through the screws and into vertebrae in
      Subgroups 0, 1, 2, and 3. The pilot holes were filled with different volumes of
      PMMA (0, 1.0, 1.5, and 2.0 mL), and then the screws were inserted in Groups C0,
      C1, C2, and C3. Screw position and distribution of PMMA were evaluated
      radiographically, and axial pullout tests were performed to measure maximum axial
      pullout strength (Fmax). RESULTS: Polymethylmethacrylate surrounded the anterior
      one-third of screws in the vertebral body in Groups A1, A2, and A3; the middle
      one-third of screws in the junction area of the vertebral body and the pedicle in
      Groups B1, B2, and B3; and the full length of screws evenly in both the vertebral
      body and the pedicle in Groups C1, C2, and C3. There was no malpositioning of
      screws or leakage of PMMA in any sample. Two-way analysis of variance revealed
      that two factors-distribution and volume of PMMA-significantly influenced Fmax
      (p<.05) but that they were not significantly correlated (p=.088). Fmax values in
      groups using augmentation with PMMA values significantly improved compared with
      those in groups without PMMA (p<.05). CONCLUSIONS: Polymethylmethacrylate can
      significantly enhance the stability of different injectable pedicle screws in
      osteoporotic lumbar vertebrae, and screw stability is significantly correlated
      with the distribution pattern and the injected volume of PMMA. The closer the
      PMMA to the pedicle and the greater the quantity of injected PMMA, the greater is
      the pedicle screw stability. Injection of 2.0 mL of PMMA through screws with four
      lateral 180 degrees  holes or of 1.0 mL of PMMA through screws with six lateral
      180 degrees  holes increases the stability of pedicle screws.

PMID- 29567518
TI  - Three new platinum complexes containing fluoroquinolones and DMSO: Cytotoxicity
      and evaluation against drug-resistant tuberculosis.
AB  - This work describes the synthesis, characterization and biological evaluation of
      three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in which L represents a
      fluoroquinolone, namely, ciprofloxacin (cpl), ofloxacin (ofl), or sparfloxacin
      (spf). The new complexes were characterized by elemental analysis, high
      resolution mass spectrometry (HRESIMS) and 1H, 13C and 195Pt NMR (nuclear
      magnetic resonance). The spectral data suggest that the fluoroquinolones act as
      bidentate ligands coordinated to Pt(II) through the nitrogen atoms of the
      piperazine ring. Microbiological assays against wild type Mycobacterium
      tuberculosis (ATCC 27294) showed that all complexes have been very potent,
      exhibiting antitubercular potency at concentrations <2 MUM, although none of the
      complexes presented higher potency than established anti-TB drugs. As to the
      resistant strains, the complex with sparfloxacin, [Pt(DMSO)(spf)Cl]Cl exhibited
      the best potential against most Mycobacterium tuberculosis clinical isolates. The
      cytotoxicity of these compounds was also evaluated in three breast cell lines:
      MCF-10 (a healthy cell), MCF-7 (a hormone responsive cancer cell) and MDA-MB-231
      (triple negative breast cancer cell). In both tumor cell lines,
      [Pt(DMSO)(spf)Cl]Cl was more active and more selective than cisplatin. Flow
      cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell
      death in MDA-MB-231 cells.

PMID- 29567519
TI  - Modification of the screw hole structures to improve the fatigue strength of
      locking plates.
AB  - BACKGROUND: The fatigue fracture of locking plates can substantially threaten
      fracture treatment results. In the present study, three measures for modifying
      the screw hole structures of plates were implemented to improve their fatigue
      strength. MATERIALS: Custom-made identical titanium locking plates, except the
      screw hole configurations, were tested using four-point bending load. The three
      measures were partial removal of screw threads on the tension side of the plates,
      reduction of screw hole size, and modification of the thread radii. There were
      six types of plates: control (Type I), half of the threads removed (Type II) or
      one-third of the threads (Type III), smaller screw holes (Type IV), and increase
      of the thread root radii (Type V) or crest radii (Type VI). FINDINGS: Compared
      with the control, Types II and III significantly improved the fatigue strength
      (14.5 and 10.1 times, respectively). Decreasing the size of the screw hole (Type
      IV) also yielded a higher fatigue strength (17.6%). Type VI significantly
      improved the fatigue strength (9.8 times). However, Type V decreased the fatigue
      strength (14%). For cyclic stiffness, Type IV was significantly higher than other
      types statistically. Failure analyses showed typical fatigue fracture in all
      plates and the cracks were always initiated at the thread crest. INTERPRETATIONS:
      The fatigue strength of titanium locking plates can be significantly improved by
      structural changes in the screw holes. Removing the threads of the plates and
      increasing the crest radii of the threads were more effective measures than
      decreasing the size of the screw holes.

PMID- 29567520
TI  - Removal of binary Cr(VI) and Cd(II) from the catholyte of MFCs and determining
      their fate in EAB using fluorescence probes.
AB  - Electrochemically active bacteria (EAB) on the cathodes of microbial fuel cells
      (MFCs) can remove metals from the catholyte, but the fate of metals in the cells
      has not been examined in the presence of multiple metals. To study the relative
      uptake and fate of Cr(VI) and Cd(II) in cells, fluorescence probes were used to
      determine the amount and location of these metals in four different EAB on the
      biocathodes of MFCs. When both metals were present, less Cr(VI) was removed but
      Cd(II) uptake was not appreciably affected. As a consequence, the imaging of
      Cr(III) ions was lower than that using individual fluorescence probes for single
      Cr(III) ions in each EAB, compared to negligible changes in images for Cd(II)
      ions in the presence of either both Cr(VI) and Cd(II) or Cd(II) alone. The
      concentration of Cr(III) ions in the cells consistently increased over time,
      while that of Cd(II) ions decreased following an initial increase. Cr or Cd
      uptake could not be detected using a scanning electron microscope coupled with an
      energy dispersive spectrometer, reflecting the high sensitivities of the
      fluorescence probes to these metals. More chromium was found in the cytoplasm
      while cadmium preferentially accumulated in the cell envelope. These results
      demonstrate that the fate of chromium and cadmium in EAB was different when both
      metals were present, compared to controls containing a single metal. These
      results provide direct and visible results on the fate of the metals in the EAB
      when these metals are co-present in the catholyte of MFCs.

PMID- 29567521
TI  - Changes in the structural features of osteoarthritis in a year of weight loss.
AB  - OBJECTIVE: In patients undergoing bariatric surgery or medical management for
      obesity, we assessed whether those experiencing substantial weight loss had
      changes in innervated knee structures or in cartilage. METHODS: Severely obese
      patients (body mass index (BMI) >=35) with knee pain on most days were seen
      before bariatric surgery or medical weight management and at 1-year follow-up.
      Examinations included 3T MRI acquired at both time points for semi-quantitative
      scoring of bone marrow lesions (BML), synovitis, cartilage damage, and for
      quantitative measurement of cartilage thickness. Association of >=20% vs <20%
      weight loss with change in semi-quantitative scores was evaluated using linear
      mixed-effects models, and that with cartilage thickness change used non
      parametric and parametric methods. Sensitivity analyses tested different
      thresholds for weight loss, weight loss as a continuous measure, examined those
      with and without bariatric surgery, and with worse osteoarthritis (OA). RESULTS:
      75 subjects (median age 49 years, 92% women) were included. At baseline, 61
      subjects (81%) had Kellgren and Lawrence (KL) grade >0, and 16 (21%) had KL grade
      >=3; 69 (92%) had cartilage damage. For BML, synovitis, and cartilage damage, the
      majority of knees had change in semi-quantitative scores of 0, and there was no
      difference between those with and without >=20% weight loss. Similarly, in terms
      of cartilage thickness loss, in 14 of 16 sub-regions thickness loss was not
      associated with weight loss. Sensitivity analyses showed similar findings.
      CONCLUSION: In middle-aged persons with mostly mild radiographic OA, structural
      features changed little over a year and weight loss was not associated with
      effects on structural changes.

PMID- 29567522
TI  - Chelation of heavy group 2 (radio)metals by p-tert-butylcalix[4]arene-1,3-crown-6
      and logK determination via NMR.

PMID- 29567523
TI  - Surface speciation of phosphate on goethite as seen by InfraRed Surface
      Titrations (IRST).
AB  - Phosphate adsorption at the metal oxide-water interface has been intensely
      studied, and the system phosphate-goethite in aqueous media is normally used as a
      model system with abundant information regarding adsorption-desorption under very
      different conditions. In spite of this, there is still discussion on whether the
      main inner-sphere surface complexes that phosphate forms on goethite are
      monodentate or bidentate. A new spectroscopic technique, InfraRed Surface
      Titration (IRST), is presented here and used to systematically explore the
      surface speciation of phosphate on goethite in the pH range 4.5-9.5 at different
      surface coverages. IRST enabled to construct distribution curves of surface
      species and distribution curves of dissolved phosphate species. In combination
      with the CD-MUSIC surface complexation model it was possible to conclude that
      surface complexes are monodentate. Very accurate distribution curves were
      obtained, showing a crossing point at pH5.5 at a surface coverage of 2.0MUmolm-2,
      with a mononuclear monoprotonated species predominating at pH>5.5 and a
      mononuclear diprotonated species prevailing at pH<5.5. On the contrary, at the
      low surface coverage of 0.7MUmolm-2 there is no crossing point, with the
      mononuclear monoprotonated species prevailing at all pH. IRST can become a
      powerful technique to investigate structure, properties and reactions of any IR
      active surface complex at the solid-water interface.

PMID- 29567524
TI  - Association of depression with body mass index classification, metabolic disease,
      and lifestyle: A web-based survey involving 11,876 Japanese people.
AB  - Body mass index (BMI) and lifestyle-related physical illnesses have been
      implicated in the pathology of depression. We aimed to investigate the
      association of depression wih BMI classification (i.e., underweight, normal,
      overweight, and obese), metabolic disease, and lifestyle using a web-based survey
      in a large cohort. Participants were 1000 individuals who have had depression
      (mean age: 41.4 +/- 12.3 years, 501 men) and 10,876 population-based controls
      (45.1 +/- 13.6 years, 5691 men). The six-item Kessler scale (K6) test was used as
      a psychological distress scale. Compared to in the controls, obesity and
      hyperlipidemia were more common and frequency of a snack or night meal
      consumption was higher, whereas frequencies of breakfast consumption and vigorous
      and moderate physical activities were lower in the patients. K6 test scores were
      higher for underweight or obese people compared to normal or overweight people. A
      logistic regression analysis showed that the K6 test cut-off score was positively
      associated with being underweight, hyperlipidemia, and the frequency of a snack
      or night meal consumption, whereas it was negatively associated with the
      frequency of breakfast consumption in the patients. Logistic regression analyses
      showed that self-reported depression was positively associated with metabolic
      diseases and the frequency of a snack or night meal consumption, whereas it was
      negatively associated with the frequency of breakfast consumption. The observed
      associations of depression with BMI classification, metabolic disease, and
      lifestyle suggest that lifestyle and related physical conditions are involved in
      at least a portion of depressive disorders.

PMID- 29567525
TI  - Perceived stigma and associated factors among children and adolescents with
      epilepsy in south western Uganda: A cross sectional study.
AB  - PURPOSE: To determine the prevalence of perceived stigma and its associated
      factors among children and adolescents with epilepsy in southwestern Uganda.
      METHODS: We conducted a cross sectional study at a large referral hospital and a
      small rural health facility in Mbarara district, southwestern Uganda.
      Participants were aged 6-18 years being managed for epilepsy for at least 3
      months, with no medical emergencies. Perceived stigma was measured using the
      Kilifi Stigma Scale of Epilepsy. Data on associated factors were collected by a
      pre-piloted investigator designed questionnaire. Logistic regression was used to
      determine associated factors considering 5% statistical significance. RESULTS:
      Prevalence of high perceived stigma was 34% with higher levels among older
      children and adolescents. Children who had never attended school were more likely
      to report perceived stigma (62%). Factors associated with this stigma included
      having epilepsy related injuries or deformities (p = 0.022), other chronic
      illnesses (p = 0.009) and a longer duration of antiepileptic drug use (p =
      0.004). CONCLUSIONS: Perceived stigma of epilepsy remains a major public health
      problem among children and adolescents and it is highly associated with
      preventable or modifiable factors. Therefore, there is need to design
      interventions that can address these factors in order to reduce the stigma and
      its potential future complications such as educational inequalities.

PMID- 29567526
TI  - Effect of modifications in mineralized collagen fibril and extra-fibrillar matrix
      material properties on submicroscale mechanical behavior of cortical bone.
AB  - A key length scale of interest in assessing the fracture resistance of bone is
      the submicroscale which is composed of mineralized collagen fibrils (MCF) and
      extra-fibrillar matrix (EFM). Although the processes through which the
      submicroscale constituents of bone contribute to the fracture resistance in bone
      have been identified, the extent of the modifications in submicroscale mechanical
      response due to the changes in individual properties of MCFs and EFM has not been
      determined. As a result, this study aims to quantify the influence of individual
      MCF and EFM material property modifications on the mechanical behavior (elastic
      modulus, ultimate strength, and resistance to failure) of bone at the
      submicroscale using a novel finite element modeling approach that incorporate 3D
      networks of MCFs with three different orientations as well as explicit
      representation of EFM. The models were evaluated under tensile loading in
      transverse (representing MCF separation) and longitudinal (representing MCF
      rupture) directions. The results showed that the apparent elastic modulus at the
      submicroscale under both loading directions for all orientations was only
      affected by the change in the elastic modulus of MCFs. MCF separation and rupture
      strengths were mainly dependent on the ultimate strength of EFM and MCFs,
      respectively, with minimal influence of other material properties. The extent of
      damage during MCF separation increased with increasing ultimate strength of EFM
      and decreased with increasing fracture energy of EFM with minimal contribution
      from elastic modulus of MCFs. For MCF rupture, there was an almost one-to-one
      linear relationship between the percent change in fracture energy of MCFs and the
      percent change in the apparent submicroscale fracture energy. The ultimate
      strength and elastic modulus of MCFs had moderate to limited influence on the MCF
      rupture fracture energy. The results of this study quantified the extent of
      changes that may be seen in the energy dissipation processes during MCF rupture
      and separation relative to the changes in the individual constituents of the
      tissue. This new knowledge significantly contributes to improving the
      understanding of how the material property alterations at the submicroscale that
      can occur due to diseases, age-related changes, and treatments affect the
      fracture processes at larger length scales.

PMID- 29567527
TI  - Improving surface wettability and lubrication of polyetheretherketone (PEEK) by
      combining with polyvinyl alcohol (PVA) hydrogel.
AB  - Poor surface wettability and relative high friction coefficients of pristine
      polyetheretherketone (PEEK) have limited its application in orthopedic implants.
      In this study, inspired by the structure of natural articular cartilage, we
      presented a novel method to fabricate a "soft-on-hard" structure on the surface
      of pristine PEEK specimens, which combined a soft polyvinyl alcohol (PVA)
      hydrogel layer and a three-dimensional porous layer with PEEK substrates. A
      variety of analytical methods were used to evaluate their properties, our results
      demonstrated that the hydrogel layer could be seamlessly connected with
      substrate, and the hydrogel-covered PEEK owned a highly hydrophilic surface, a
      very low water contact angle of 7 degrees  could be obtained. The friction
      coefficients of untreated and hydrogel-covered PEEK surfaces were measured using
      a tribometer under water lubrication, due to the presence of the top hydrogel
      layer and the hard substrate could provide excellent aqueous lubrication and
      bearing capacity, respectively, the friction coefficient could be reduced from
      0.292 to 0.021. In addition, the porous layer under PVA hydrogel layer could work
      as gel reservoirs, the reserved hydrogel would be released after the surface
      layer was sheared off, and a regenerable lubrication status was obtained. This
      work provides a new route for the design of improving the surface wettability and
      tribological properties of PEEK.

PMID- 29567528
TI  - Nano-scale mechanical behavior of pre-crystallized CAD/CAM zirconia-reinforced
      lithium silicate glass ceramic.
AB  - This paper reports on the mechanical behavior of pre-crystallized CAD/CAM
      zirconia-reinforced lithium silicate glass ceramic (ZLS) using nanoindentation
      with a Berkovich diamond tip and in situ scanning probe microscopy (SPM). The
      indentation contact hardness, the elastic modulus, and the elasticity and
      plasticity of the material were determined using the Oliver-Pharr method, the
      Sakai model and the Meyer's law at peak loads of 2.5-10 mN and a loading rate of
      0.5 mN/s. The load-displacement curves at all applied loads indicate that ZLS
      deformed plastically without fracture. The discrete discontinuities in the load
      displacement curves might have arisen from the shear plane activation for plastic
      deformation. The measured hardness and elastic modulus were load-independent
      (ANOVA, p > 0.05), in ranges of 8.17 +/- 1.23 GPa to 9.86 +/- 1.24 GPa and 98.55
      +/- 7.38 GPa to 105.78 +/- 9.98 GPa, respectively. The resistance to plasticity
      of ZLS significantly showed a second-order polynomial load relationship or a
      power law load dependency. Meanwhile, both the elastic and plastic displacements
      also significantly revealed power law load dependencies. However, the elastic and
      plastic deformation components were load-independent. Increased indentation loads
      resulted in significant decreases in the normalized elastic strain energy (p <
      0.05) accompanied by significant increases in the normalized indentation absorbed
      energy (p < 0.05). The equivalent elasticity and plasticity of ZLS during
      indentation occurred at 7.5 mN. The outcomes of this study provide insights into
      fabrication and mechanical functions of ZLS restorations, particularly
      facilitating abrasive machining in dental CAD/CAM processing in the ductile
      regime.

PMID- 29567529
TI  - Characterization of the anisotropic mechanical behavior of human abdominal wall
      connective tissues.
AB  - Abdominal wall sheathing tissues are commonly involved in hernia formation.
      However, there is very limited work studying mechanics of all tissues from the
      same donor which prevents a complete understanding of the abdominal wall behavior
      and the differences in these tissues. The aim of this study was to investigate
      the differences between the mechanical properties of the linea alba and the
      anterior and posterior rectus sheaths from a macroscopic point of view. Eight
      full-thickness human anterior abdominal walls of both genders were collected and
      longitudinal and transverse samples were harvested from the three sheathing
      connective tissues. The total of 398 uniaxial tensile tests was conducted and the
      mechanical characteristics of the behavior (tangent rigidities for small and
      large deformations) were determined. Statistical comparisons highlighted
      heterogeneity and non-linearity in behavior of the three tissues under both small
      and large deformations. High anisotropy was observed under small and large
      deformations with higher stress in the transverse direction. Variabilities in the
      mechanical properties of the linea alba according to the gender and location were
      also identified. Finally, data dispersion correlated with microstructure revealed
      that macroscopic characterization is not sufficient to fully describe behavior.
      Microstructure consideration is needed. These results provide a better
      understanding of the mechanical behavior of the abdominal wall sheathing tissues
      as well as the directions for microstructure-based constitutive model.

PMID- 29567530
TI  - A combined strategy to enhance the properties of Zn by laser rapid solidification
      and laser alloying.
AB  - The orthopedic application of Zn is limited owing to the poor strength and low
      plasticity. In this study, a novel strategy by combining rapid solidification
      obtained by selective laser melting (SLM) and alloying with Mg was proposed to
      improve the mechanical properties of Zn. The microstructures, mechanical
      properties, as well as in vitro cytocompatibility of SLM processed Zn-xMg (x = 0
      4 wt%) were studied systematically. Results shown that SLM processed Zn-xMg
      alloys consisted of fine equiaxed alpha-Zn grains with homogeneously precipitated
      Mg2Zn11 along grain boundaries. More importantly, the grains size of alpha-Zn was
      decreased from 104.4 +/- 30.4 um to 4.9 +/- 1.4 um with Mg increasing. And Mg
      mainly dissolved in alpha-Zn developing into supersaturated solid solution due to
      rapid solidification effect. As a consequence, the ultimate tensile strength and
      elongation were enhanced by 361% and 423%, respectively, with Mg containing up to
      3 wt%. Meanwhile, alloying with Mg enhanced the corrosion resistance of Zn, with
      the degradation rate decreasing from 0.18 +/- 0.03 mm year-1 to 0.10 +/- 0.04 mm
      year-1. Furthermore, SLM processed Zn-xMg exhibited good biocompatibility. This
      research suggested that SLM processed Zn-3Mg alloy was a potential biomaterial
      for orthopedic applications.

PMID- 29567531
TI  - Nondegradable magnetic poly (carbonate urethane) microspheres with good shape
      memory as a proposed material for vascular embolization.
AB  - In this study, nondegradable poly (carbonate urethane) (PCU) and poly (carbonate
      urethane) incorporated variable Fe3O4 content microspheres (PCU/Fe3O4) were
      synthesized using pre-polymerization and suspension polymerization. Synthesis was
      confirmed through Fourier transform infrared spectroscopy (FTIR). The effect of
      Fe3O4 incorporation was investigated on crystalline, thermal, shape memory and
      degradation properties by X-Ray diffraction (XRD), Differential scanning
      calorimetery (DSC), compression test and degradation in vitro, respectively.
      Otherwise, the assessment of magnetic characteristics by vibrational sample
      magnetometry (VSM) disclosed superparamagnetic behavior. The tunable
      superparamagnetic behavior depends on the amount of magnetic particles
      incorporated within the networks. The biological study results of as-synthesized
      polymers from the platelet adhesion test and the cell proliferation inhibition
      test indicated they were biocompatible in vitro. Fe3O4 incorporation was
      conductive to reducing platelet adhesion in blood contacting test and promotion
      of rat vascular smooth muscle cell proliferation and growth. These nondegradable,
      superparamagnetic, biocompatible polymers, combined with their good shape memory
      properties may allow for their future exploitation in the biomedical field, such
      as, in cardiovascular implants, targeted tumor treatment, tissue engineering and
      artificial organ's engineering.

PMID- 29567532
TI  - Adaptive Bayesian inference system for recognition of walking activities and
      prediction of gait events using wearable sensors.
AB  - In this paper, a novel approach for recognition of walking activities and gait
      events with wearable sensors is presented. This approach, called adaptive
      Bayesian inference system (BasIS), uses a probabilistic formulation with a
      sequential analysis method, for recognition of walking activities performed by
      participants. Recognition of gait events, needed to identify the state of the
      human body during the walking activity, is also provided by the proposed method.
      In addition, the BasIS system includes an adaptive action-perception method for
      the prediction of gait events. The adaptive approach uses the knowledge gained
      from decisions made over time by the inference system. The action-perception
      method allows the BasIS system to autonomously adapt its performance, based on
      the evaluation of its own predictions and decisions made over time. The proposed
      approach is implemented in a layered architecture and validated with the
      recognition of three walking activities:level-ground, ramp ascent and ramp
      descent. The validation process employs real data from three inertial
      measurements units attached to the thigh, shanks and foot of participants while
      performing walking activities. The experiments show that mean decision times of
      240 ms and 40 ms are needed to achieve mean accuracies of 99.87% and 99.82% for
      recognition of walking activities and gait events, respectively. The validation
      experiments also show that the performance, in accuracy and speed, is not
      significantly affected when noise is added to sensor measurements. These results
      show that the proposed adaptive recognition system is accurate, fast and robust
      to sensor noise, but also capable to adapt its own performance over time.
      Overall, the adaptive BasIS system demonstrates to be a robust and suitable
      computational approach for the intelligent recognition of activities of daily
      living using wearable sensors.

PMID- 29567533
TI  - High salt diet induces metabolic alterations in multiple biological processes of
      Dahl salt-sensitive rats.
AB  - High salt induced renal disease is a condition resulting from the interactions of
      genetic and dietary factors causing multiple complications. To understand the
      metabolic alterations associated with renal disease, we comprehensively analyzed
      the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS)
      rats using GC-MS technology and biochemical analyses. Physiological features,
      serum chemistry, and histopathological data were obtained as complementary
      information. Our results showed that high salt (HS) intake for 16 weeks caused
      significant metabolic alterations in both the renal medulla and cortex involving
      a variety pathways involved in the metabolism of organic acids, amino acids,
      fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase,
      phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed
      the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up
      regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase
      and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP+, NADPH oxidase
      activity and ROS production, suggesting that increased oxidative stress was
      associated with an altered PPP pathway. The metabolic pathways identified may
      serve as potential targets for the treatment of renal damage. Our findings
      provide comprehensive biochemical details about the metabolic responses to a high
      salt diet, which may contribute to the understanding of renal disease and salt
      induced hypertension in SS rats.

PMID- 29567534
TI  - Evaluating the effects of a targeted home visiting program on maternal and child
      health outcomes.
AB  - We evaluate the effects of home visiting targeted towards disadvantaged first
      time mothers on maternal and child health outcomes. Our analysis exploits a
      randomized controlled trial and combines rich longitudinal survey data with
      unique administrative health data. In a context in which the target group has
      comprehensive health care access, we find no effects of home visiting on most
      types of health utilization, health behaviors, and physical health measures.
      However, the intervention has a positive effect on some maternal mental health
      outcomes, reducing depression reported in the survey data by eleven percentage
      points and prescription of psycholeptics recorded in the administrative data by
      seven percentage points.

PMID- 29567535
TI  - Nanobodies targeting cortactin proline rich, helical and actin binding regions
      downregulate invadopodium formation and matrix degradation in SCC-61 cancer
      cells.
AB  - Cortactin is a multidomain actin binding protein that activates Arp2/3 mediated
      branched actin polymerization. This is essential for the formation of protrusive
      structures during cancer cell invasion. Invadopodia are cancer cell-specific
      membrane protrusions, specialized at extracellular matrix degradation and
      essential for invasion and tumor metastasis. Given the unequivocal role of
      cortactin at every stage of invadopodium formation, it is considered an
      invadopodium marker and potential drug target. We used cortactin nanobodies to
      examine the role of cortactin domain-specific function at endogenous protein
      level. Two cortactin nanobodies target the central region of cortactin with high
      specificity. One nanobody interacts with the actin binding repeats whereas the
      other targets the proline rich region and was found to reduce EGF-induced
      cortactin phosphorylation. After intracellular expression as an intrabody, they
      are both capable of tracing their target in the complex environment of the
      cytoplasm, and disturb cortactin functions during invadopodia formation and
      extracellular matrix degradation. These data illustrate the use of nanobodies as
      a research tool to dissect the role of cortactin in cancer cell motility. This
      information can contribute to the development of novel therapeutics for tumor
      cell migration and metastasis.

PMID- 29567536
TI  - Role of lncRNAs in the cancer development and progression and their regulation by
      various phytochemicals.
AB  - Long non coding RNAs (lncRNAs) are involved in modulating the expression of other
      non-coding RNAs (ncRNA), such as microRNAs, or target proteins through the
      epigenetic, transcriptional, or post-transcriptional regulations. Genomic
      mutations in cancer reside inside regions that do not code for proteins and these
      regions are often transcribed into long non coding RNAs (lncRNAs). Emerging
      evidences have revealed an intense involvement of lncRNAs in the cancer
      development and progression. Recently, emerging evidences have depicted that the
      phytochemicals interact with lncRNAs to modulate their activities. Such findings
      are highly important for the identification of therapeutic strategies against
      diseases that are particularly associated with an aberrant lncRNA signaling. This
      review aims at deciphering the role of lncRNAs in the cancer development and
      progression, and their regulation by various phytochemicals.

PMID- 29567537
TI  - Trans-anethole prevents hypertension induced by chronic exposure to both
      restraint stress and nicotine in rats.
AB  - Chronic stress and smoking are major risk factors for hypertension, with stress
      also being a factor predisposing to smoking. Methods are needed to prevent and/or
      reduce hypertension induced by chronic exposure to both stress and nicotine. This
      study investigated whether trans-anethole would prevent hypertension induced by
      chronic exposure to both restraint stress and nicotine in rats. Rats received
      nicotine intraperitoneally for 21 days following restraint stress (2 h/day) and
      trans-anethole (62, 125, and 250 mg/kg) on days 4, 8, 12, 16 and 20. To confirm
      the preventive effects of trans-anethole, blood pressure and vascular tone were
      measured on the last day of the experiment, and compared with the results of
      nifedipine and aerobic exercise. The ability of trans-anethole, at doses of 125
      mg/kg and 250 mg/kg, to prevent hypertension was comparable to that of aerobic
      exercise and nifedipine. Furthermore, nifedipine combined with aerobic exercise
      and trans-anethole reduced both blood pressure and vascular tone. These findings
      are the first to show that trans-anethole can prevent hypertension, suggesting
      that trans-anethole may be useful as a prophylactic antihypertensive agent.

PMID- 29567538
TI  - Current approaches for the treatment of premature ovarian failure with stem cell
      therapy.
AB  - One of the common disorders found in women is premature ovarian failure (POF).
      Recently some studies have explained premature ovarian insufficiency (POI). The
      causes of it are unknown although various types of study have been done. The most
      common causes such as genetic and autoimmune conditions can have a role in POF
      and can lead to infertility. Some characterization of POF are hypo-oestrogenism
      (estrogen deficiency), increased gonadotropin level and most importantly
      amenorrhea. The main purpose of this review is to describe the cause and
      treatment of POF, especially stem cell therapy proposed in previous studies. Stem
      cells have self-renewal and regeneration potential, hence they can be very
      effective in the treatment of ovarian failure and consequently infertility. There
      are several kinds of stem cells such as, mesenchymal stem cells (MSCs), stem
      cells from extra-embryonic tissues, induced pluripotent stem cells (iPSCs), and
      ovarian stem cells that are used in POF stem cell therapy as observed in previous
      studies. This article reviews the latest studies on POF to summarize current
      understanding and future directions.

PMID- 29567539
TI  - Metformin inhibits glioma cells stemness and epithelial-mesenchymal transition
      via regulating YAP activity.
AB  - This work aims to study the roles and mechanisms of metformin in glioma cells
      stemness and epithelial-mesenchymal transition. Here, we found that metformin
      suppressed glioma cells spheroid formation and size, inhibited the expression of
      glioma stemness-related marker, CD133. Additionally, Metformin attenuated TGF
      beta-induced epithelial-mesenchymal transition in glioma cells. Mechanistically,
      metformin inhibited the nuclear abundance of YAP, a key effector of Hippo
      pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP
      transcriptional modulating activity. Importantly, overexpression of a mutant form
      of YAP (YAP-5SA) attenuated the inhibition of metformin on glioma cells stemness
      and epithelial-mesenchymal transition. Thus, metformin inhibits glioma cells
      stemness and epithelial-mesenchymal transition via regulating YAP activity.

PMID- 29567540
TI  - Silencing ZAP70 prevents HSP65-induced reverse cholesterol transport and NF
      kappaB activation in T cells.
AB  - T cell activation by antigens binding to the T cell receptor (TCR) must be
      properly regulated to ensure normal T cell development. The zeta chain-associated
      70-kDa protein (ZAP70) is sequentially activated in response to TCR engagement
      and serves as a critical component of the TCR signaling pathway, which is
      essential for T cell activation. However, some roles of ZAP70 have not been fully
      elucidated. In the present study, we analyzed the effects of ZAP70 on the
      cholesterol efflux rate, nuclear factor kappaB (NF-kappaB) activation and cell
      proliferation in T cells. Our study showed that silencing ZAP70 increased the
      cholesterol efflux rate in T cells. We also found that silencing ZAP enhanced the
      expression of ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette
      transporter G1 (ABCG1), scavenger receptor-BI (SR-BI) peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) and liver X receptor-alpha (LXR-alpha). In
      contrast, the phosphorylation of ZAP70 by HSP65 decreased the cholesterol efflux
      rate and the expression of five cholesterol transport proteins in T cells. The
      phosphorylation of ZAP70 activated the downstream NF-kappaB signaling pathway,
      which is involved in both T cell growth and function. Furthermore, silencing
      ZAP70 inhibited T cell proliferation. These results indicate a crucial and
      unexpected role for ZAP70 in the physiological activities of T cells, suggesting
      that inhibition of ZAP70 is beneficial for anti-atherosclerosis.

PMID- 29567541
TI  - Epiisopiloturine, an imidazole alkaloid, reverses inflammation and lipid
      peroxidation parameters in the Crohn disease model induced by
      trinitrobenzenosulfonic acid in Wistar rats.
AB  - Epiisopiloturine (EPI) is an important imidazole alkaloid because of its
      pharmacological properties. The aim of this study was to investigate the effects
      of epiisopiloturine on inflammatory parameters of the colonic mucosa in a rat
      model of Crohn's disease (CD). For this, we induced colitis using
      trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1
      beta (IL-1beta), glutathione (GSH), and malondialdehyde (MDA) levels in the
      intestinal mucosa. The location and expression of the inflammatory markers in the
      colon were investigated by immunohistochemistry for NO synthase induced (iNOS),
      interleukin 1 beta (IL-1beta), and cyclooxygenase-2 (COX-2) and western blotting
      (iNOS and COX-2), respectively. Compared with TNBS alone, epiisopiloturine at 1
      mg/kg reduced the macroscopic and microscopic scores, wet weight of the colon,
      and neutrophilic infiltration and expression of the pro-inflammatory cytokine IL
      1beta. Epiisopiloturine at 1 mg/kg maintained or restored GSH levels and
      simultaneously decreased MDA levels. Animals treated with epiisopiloturine
      exhibited reduced immunostaining for IL-1beta, iNOS, and COX-2 and reduced cell
      count per field. Epiisopiloturine reduced the expression of COX-2 and iNOS in the
      colon. Based on these findings, we conclude that epiisopiloturine at 1 mg/kg may
      be an important pharmacological tool against intestinal inflammatory diseases due
      to its inhibitory action on key enzymes and products involved in inflammation.

PMID- 29567542
TI  - MicroRNA-132 and microRNA-212 mediate doxorubicin resistance by down-regulating
      the PTEN-AKT/NF-kappaB signaling pathway in breast cancer.
AB  - Breast cancer is a serious health problem worldwide. Acquisition of multi-drug
      resistance (MDR) during the treatment of breast cancer is still considered a
      major clinical obstacle. Despite the biological functions of miRNAs becoming
      increasingly apparent, the function of miRNAs in regulating drug resistance of
      breast cancer remains under investigation. Quantitative real-time PCR (qRT-PCR)
      was used to quantify the expression of miR-132/-212 (miR-132 and miR-212) in
      doxorubicin (DOX)-resistant and -sensitive breast cancer tumors and cells. The
      function of miR-132/-212 in drug resistance was investigated in vitro (MTT assay,
      TUNEL assay, fluorescence, immunohistochemistry, luciferase reporter assay,
      Western blotting). We found that miR-132/-212 were commonly overexpressed in DOX
      resistant breast cancer tumors and cells. Silenced miR-132/-212 expression
      induced DOX accumulation in MCF-7/ADR cells, while overexpression of miR-132/-212
      led to breast cancer resistance protein (BCRP)-based DOX efflux in MCF-7 cells.
      Further study showed that up-regulation of miR-132/-212 in MCF-7/ADR cells
      suppressed the expression of PTEN, a target gene of miR-132/-212, which activated
      AKT phosphorylation and the NF-kappaB pathway and led to increased BCRP
      expression. Down-regulation of miR-132/-212 sensitized MCF-7/ADR cells to DOX.
      Mechanistic investigations suggested that miR-132/-212 enhancement was a result
      of NF-kappaB-mediated transactivation of the pri-miR-132/-212 gene. Taken
      together, our findings are among the first to demonstrate a novel aspect of the
      miR-132/-212-PTEN-AKT/NF-kappaB-BCRP pathway in the generation of breast cancer
      resistance and provides a potential method to reverse drug resistance.

PMID- 29567543
TI  - Astragalus polysaccharide protects hypoxia-induced injury by up-regulation of miR
      138 in rat neural stem cells.
AB  - Astragalus polysaccharide (APS) is the main active ingredient of astragalus and
      exhibits various pharmacological effects. This study aimed to investigate the
      effect of APS on hypoxia-induced injury in neural stem cells (NSCs). The NSCs
      derived from the hippocampus of rat were subjected to hypoxia incubator to
      establish a hypoxia model. NSCs were pretreated with APS before hypoxia injury to
      investigate the effect of APS. The expression of miR-138 was inhibited by
      transfection with miR-138 inhibitor and the miR-138 level was measured by qRT
      PCR. Cell viability and apoptotic cell rates were respectively assessed by CCK-8
      assay and flow cytometry assay. Western blot was performed to determine the
      expression of apoptosis-, JNK pathway- and p38MAPK pathway-related factors.
      Hypoxia exposure caused the reduction of cell viability and induction of cell
      apoptosis of NSCs. However, APS pretreatment attenuated the cell injury induced
      by hypoxia, as evidenced by increased cell viability, reduced apoptotic cells,
      inhibited expression of pro-apoptotic factors and enhanced expression of anti
      apoptotic factor. Interestingly, higher miR-138 expression was observed in the
      hypoxia-injured NSCs compared with normoxia, and miR-138 expression was further
      up-regulated by APS pretreatment. Furthermore, miR-138 inhibitor blocked the
      protective effect of APS on hypoxia-injured NSCs. In addition, we found that APS
      inhibited the JNK and p38MAPK pathways through miR-138. In conclusion, this study
      demonstrated a protective effect of APS on hypoxia-induced NSC injury. The
      regulatory mechanism might be mediated by up-regulation of miR-138 and inhibition
      of the JNK and p38MAPK pathways.

PMID- 29567544
TI  - Estimating age and synthesising growth in children and adolescents using 3D
      facial prototypes.
AB  - 3D facial images are becoming increasingly common. They provide more information
      about facial form than their 2D counterparts and will be useful in future
      forensic applications. These include age estimation and predicting changes in
      appearance of missing persons (synthetic growth). We present a framework for both
      age estimation and synthetic growth of children and adolescents from 3D
      photographs. Age estimation accuracy was substantially better than for existing
      approaches (mean absolute error=1.19 years). Our synthetically 'grown' images
      were compared to actual longitudinal images of the same cases. On average 75% of
      the head overall and 85% of the face were predicted correctly to within three
      millimetres. We find that our approach is most suitable for ageing children from
      late childhood into adolescence. The work can be improved in the future by
      modelling skin colouring and taking account of other factors that influence face
      shape such as BMI.

PMID- 29567545
TI  - A commentary on the effects of methamphetamine and the status of methamphetamine
      abuse among youths in South Korea, Japan, and China.
AB  - Methamphetamine (MA) abuse continues in East Asia and shows an increasing trend
      among youths in South Korea, Japan, and China. Although the negative effects of
      MA abuse on youth are considered as significant problems, few studies have been
      conducted on the topic in these countries. This paper focuses on the effects of
      MA on the human body and current MA abuse among youths in South Korea, Japan, and
      China. To investigate the negative effects of MA on the human body, we searched
      the keywords "MA," "human," and "effect" for studies published from 2013 to 2017.
      MA activates the neurotransmitter system and the central nervous system, and when
      used at high dosage or for long term, MA can cause severe neurotoxicity and
      cardiovascular problems. Online networks contribute to MA abuse by sharing
      methods for preparing synthetic MA. Despite efforts to reduce MA abuse, social
      crimes associated with its abuse continue and numbers of illegal MA users are
      increasing steadily in Korea, Japan, and China. In young users, diverse factors
      associated with drug addiction, such as curiosity and peer effect, lead to MA
      abuse and its attendant personal and social problems.

PMID- 29567546
TI  - Body image related negative interpretation bias in anorexia nervosa.
AB  - A distorted body image and pronounced body dissatisfaction are hallmarks of
      anorexia nervosa (AN) that typically result in dietary restraint and compensatory
      behaviours. Cognitive biases such as negative interpretation bias are considered
      key maintaining factors of these maladaptive cognitions and behaviours. However,
      little attention has been paid to empirical tests whether negative interpretation
      bias exists in AN and to what degree it is associated with symptom severity.
      Participants in the present study were 40 women with AN and 40 healthy women with
      no history of an eating disorder. Body-related negative interpretation bias
      (i.e., a tendency to interpret ambiguous information about the own body in a
      negative way) was measured by a Scrambled Sentences Task. Patients with AN showed
      a stronger body-related negative interpretation bias than healthy controls.
      Within both groups, negative interpretation bias correlated strongly and
      positively with AN symptom severity and these effects were not moderated by
      levels of depressive symptoms. The findings support the idea that biased
      interpretation of body-related information is associated with the specific
      psychopathology of AN. Targeted, computerised interventions (e.g. interpretation
      bias modification) may help to alter these dysfunctional cognitive schemas that
      lie at the heart of AN.

PMID- 29567547
TI  - Longitudinal relations among maternal depressive symptoms, maternal mind
      mindedness, and infant attachment behavior.
AB  - The relations among maternal depression risk, maternal mind-mindedness, and
      infants' attachment behavior were longitudinally examined in a community sample
      of mother-infant dyads. Maternal self-reported depression risk was measured at
      the infant ages of 6 weeks, 4 months, and 12 months. Maternal mind-mindedness,
      assessed from mothers' comments about infants' mental states (e.g., infants'
      thoughts, desires, or emotions), was measured during mother-infant interactions
      when infants were 4 months. Infants' attachment behavior was assessed at one
      year. Mothers' depression risk decreased over the infants' first year, with the
      sharpest decline between 6 weeks and 4 months. Mothers at risk for depression
      when infants were 6 weeks showed less appropriate mind-mindedness at 4 months.
      Mind-mindedness was not related to maternal depression risk at the infant age of
      4 months or 12 months. Infants' degree of disorganized attachment behavior at one
      year was positively associated with maternal depression risk at 6 weeks and
      negatively associated with maternal appropriate mind-mindedness at 4 months.
      Mothers who are at risk for depression in their infants' early lives may be
      hampered in their capacity to respond appropriately to their infants' mental
      states. Infants with mothers who have difficulty responding appropriately to
      their mental states, as suggested by low appropriate mind-mindedness, may feel
      less known and recognized by their mothers, a key theme in the origins of
      disorganized attachment.

PMID- 29567548
TI  - Analysis of proteoglycan expression in human dental pulp.
AB  - : Proteoglycans are glycosylated proteins which have covalently attached highly
      anionic glycosaminoglycans. They can be located on the extracellular matrix, cell
      membrane or intracellular granules. To date, few studies have reported the
      presence of proteoglycans in human dental pulp. OBJECTIVE: The aim of this study
      was, therefore, to analyze the expression of lumican, versican and glypican
      proteoglycans in deciduous and permanent human dental pulp by real-time
      polymerase chain reaction (q-PCR) and immunofluorescence. DESIGN: Healthy human
      dental pulps were used: 13 from permanent teeth (group 1) and eight from
      deciduous teeth (group 2). Versican, lumican and glypican (glypican-1 to 6) gene
      expressions were quantitatively evaluated by real-time PCR technique, using the
      expression of the endogenous gene GAPDH as control. Pulp sections were submitted
      to immunostaining procedure with fluorescence labelling, the tissues being fixed
      and incubated with well-characterized monoclonal and polyclonal antibodies
      against proteoglycan epitopes, including anti-versican and anti-lumican.
      Comparisons among the groups of the quantitative scores for each proteoglycan
      were analyzed using the t-test and ANOVA (P < 0.05). RESULTS: The real-time PCR
      analysis showed expression of versican and lumican proteoglycans in the two
      groups, with significant predominance of lumican gene (P = 0.03). Considering the
      glypican genes, glypican-3 was the proteoglycan most significantly expressed in
      permanent pulps (P < 0.001), while glypican-2 was not expressed in this tissue.
      The immunofluorescence quantification exhibited no significant differences
      between lumican and versican among the pulps and groups. CONCLUSIONS: The lumican
      gene was more expressed than versican and glypican-3 was the isoform more
      expressed in permanent pulp compared to deciduous.

PMID- 29567549
TI  - An Aspergillus aculateus strain was capable of producing agriculturally useful
      nanoparticles via bioremediation of iron ore tailings.
AB  - Mining waste such as iron ore tailing is environmentally hazardous, encouraging
      researchers to develop effective bioremediation technologies. Among the microbial
      isolates collected from iron ore tailings, Aspergillus aculeatus (strain T6)
      showed good leaching efficiency and produced iron-containing nanoparticles under
      ambient conditions. This strain can convert iron ore tailing waste into
      agriculturally useful nanoparticles. Fourier-transform Infrared Spectroscopy (FT
      IR analysis) established the at the particles are protein coated, with energy
      dispersive X-ray Spectroscopy (EDX analysis) showing strong signals for iron.
      Transmission Electron Microscopy (TEM analysis) showed semi-quasi spherical
      particles having average size of 15 +/- 5 nm. These biosynthesized nanoparticles
      when tested for their efficacy on seed emergence activity of mungbean (Vigna
      radiata) seeds, and enhanced plant growth at 10 and 20 ppm.

PMID- 29567550
TI  - Redirecting fire-prone Mediterranean ecosystems toward more resilient and less
      flammable communities.
AB  - The extensive abandonment of agricultural lands in the Mediterranean basin has
      led to large landscapes being dominated by early-successional species,
      characterized by high flammability and an increasing fire risk. This fact
      promotes fire occurrence and places ecosystems in a state of arrested succession.
      In this work, we assessed the effectiveness of several restoration actions in
      redirecting these ecosystems toward more resilient communities dominated by
      resprouting species. These actions included the mechanical clearing of early
      successional species, the plantation of resprouting species, and the combination
      of both treatments. For 13 years, we assessed shifts in the successional
      trajectory and ecosystem flammability by changes in: species composition, species
      richness, ecosystem evenness, the natural colonization of resprouting species,
      total biomass and proportion of dead biomass. We observed that the plantation and
      clearing combination was a suitable strategy to promote resilience. Species
      richness increased as well as the presence of the resprouting species introduced
      by planting. The natural colonization of the resprouting species was also
      enhanced. These changes in the successional trajectory were accompanied by a
      possible reduction of fire risk by reducing dead fuel proportion. These findings
      are relevant for the management of Mediterranean basin areas, but also suggest
      new tools for redirecting systems in fire-prone areas worldwide.

PMID- 29567551
TI  - Combination of ground rice husk and polyvinyl alcohol fiber in cementitious
      composite.
AB  - In this study, ground rice husks (GRH) in combination with polyvinyl-alcohol
      (PVA) fiber were used to produce low-cost and high-quality hybrid cementitious
      composites. Different amounts of GRH (2.5, 5.0, 7.5 and 12.5% in weight of
      cement) were added to the concrete. The work presented in this paper provides an
      insight into the use of an agricultural waste as effective additive in cement
      based materials. The properties of resultant cementitious composites including
      density, water absorption, flexural behavior and compressive strength were
      investigated. The results have shown that incorporation of ground rice husk in
      combination with PVA fiber can be effective in improvement of the flexural
      properties of cementitious composite. The study explored the effectiveness of
      this type of agricultural waste as a beneficial material in fine aggregate
      concrete materials.

PMID- 29567552
TI  - Nitrogen-enriched carbon sheet for Methyl blue dye adsorption.
AB  - In this work, nitrogen-enriched carbon sheet (NECS) was successfully fabricated
      by using sodium gluconate as a carbon source via melamine assisted chemical
      blowing approach. The obtained material exhibits sheet-like morphology with ultra
      thin thickness and has a high specific surface area of 604 m2g-1 and high
      nitrogen contents of 11.2 wt%. The NECS showed an excellent adsorption
      performance towards the removal of anionic dye Methyl blue (a-Mb). The adsorption
      of a-Mb onto NECS better fitted the Langmuir isotherm model with the highest
      adsorption capacity of 847 mg g-1. Interestingly, the NECS showed a pH-sensitive
      behavior towards the adsorption efficiency of a-Mb dye in which the adsorption
      capacity abruptly increased from 34 to 701 mg g-1 when the pH of the solution was
      decreased from 10 to 2. Furthermore, the adsorbed materials can be easily
      regenerated without obvious efficiency loss over a five adsorption-desorption
      cycles.

PMID- 29567553
TI  - Arsenic and fluoride removal from contaminated drinking water with Haix-Fe-Zr and
      Haix-Zr resin beads.
AB  - The objective of the study was to carry-out batch tests to examine the
      effectiveness of Haix-Fe-Zr and Haix-Zr resin beads in the removal of As(III),
      As(V) and F- from groundwater with a similar geochemistry to a site where a
      community-based drinking water plant has been installed in West Bengal, India.
      The groundwater was spiked separately with ~200 MUg/L As(III) and As(V) and 5
      mg/L F-. Haix-Zr resin beads were more effective than Haix-Fe-Zr resin beads in
      removing As(III) and As(V). Haix-Zr resin beads showed higher removal of As(V)
      compared to As(III). Haix-Zr resin beads removed As(V) below the WHO (10 MUg/L)
      drinking water standards at 8.79 MUg/L after 4 h of shaking, while As(III) was
      reduced to 7.72 MUg/L after 8 h of shaking. Haix-Fe-Zr resin beads were more
      effective in removing F- from the spiked groundwater compared to Haix-Zr resin
      beads. Concentrations of F- decreased from 6.27 mg/L to 1.26 mg/L, which is below
      the WHO drinking water standards (1.5 mg/L) for F-, after 15 min of shaking with
      Haix-Fe-Zr resin beads. After 20 min of shaking in groundwater treated with Haix
      Zr resin beads, F- concentrations decreased from 6.27 mg/L to 1.43 mg/L. In the
      removal of As(III), As(V), and F- from the groundwater, Haix-Fe-Zr and Haix-Zr
      resin beads fit the parabolic diffusion equation (PDE) suggesting that adsorption
      of these contaminants was consistent with inter-particle diffusion.

PMID- 29567554
TI  - Harnessing the bio-mineralization ability of urease producing Serratia marcescens
      and Enterobacter cloacae EMB19 for remediation of heavy metal cadmium (II).
AB  - In the present study, urease positive Serratia marcescens (NCIM2919) and
      Enterobacter cloacae EMB19 (MTCC10649) were individually evaluated for
      remediation of cadmium (II) using ureolysis-induced calcium carbonate
      precipitation. Both the cultures were observed to efficiently remove cadmium from
      the media through co-precipitation of Cd (II) and Ca (II). S. marcescens and E.
      cloacae EMB19, respectively showed 96 and 98% removal of initial 5.0 mg L-1
      soluble Cd (II) from the urea and CaCl2 laden media at 96 h of incubation period.
      At higher Cd (II) concentrations of 10 and 15 mg L-1, cadmium removal efficiency
      was much higher in case of E. cloacae EMB19 compared to S. marcescens. In-vitro
      cadmium (II) remediation study using urease containing cell-free culture
      supernatant of S. marcescens and E. cloacae EMB19 showed respective 98 and 53%
      removal of initial 50 mg L-1 Cd (II) from the reaction mixtures in co-presence of
      Ca (II). While in sole presence of Cd (II), only 16 and 8% removal of Cd (II)
      were detected for S. marcescens and E. cloacae EMB19, respectively. The elemental
      analysis of the co-precipitated mineral products using Energy Dispersive X-ray
      spectroscopy (EDX) clearly showed the prevalence of Ca and Cd ions. The
      morphology Cd-Ca composites formed with respect to both the cultures were
      observed to be of different shape and size as revealed through Scanning Electron
      Microscopy (SEM). Entire study hence comes out with a sustainable bioremediation
      option which could be effectively used to tackle Cd (II) or other heavy metal
      pollution.

PMID- 29567555
TI  - Evaluating a novel tiered scarcity adjusted water budget and pricing structure
      using a holistic systems modelling approach.
AB  - Population growth, coupled with declining water availability and changes in
      climatic conditions underline the need for sustainable and responsive water
      management instruments. Supply augmentation and demand management are the two
      main strategies used by water utilities. Water demand management has long been
      acknowledged as a least-cost strategy to maintain water security. This can be
      achieved in a variety of ways, including: i) educating consumers to limit their
      water use; ii) imposing restrictions/penalties; iii) using smart and/or efficient
      technologies; and iv) pricing mechanisms. Changing water consumption behaviours
      through pricing or restrictions is challenging as it introduces more social and
      political issues into the already complex water resources management process.
      This paper employs a participatory systems modelling approach for: (1) evaluating
      various forms of a proposed tiered scarcity adjusted water budget and pricing
      structure, and (2) comparing scenario outcomes against the traditional
      restriction policy regime. System dynamics modelling was applied since it can
      explicitly account for the feedbacks, interdependencies, and non-linear relations
      that inherently characterise the water tariff (price)-demand-revenue system. A
      combination of empirical water use data, billing data and customer feedback on
      future projected water bills facilitated the assessment of the suitability and
      likelihood of the adoption of scarcity-driven tariff options for a medium-sized
      city within Queensland, Australia. Results showed that the tiered scarcity
      adjusted water budget and pricing structure presented was preferable to
      restrictions since it could maintain water security more equitably with the
      lowest overall long-run marginal cost.

PMID- 29567556
TI  - Natural organic matter residue as a low cost adsorbent for aluminum.
AB  - The contamination of aquatic and terrestrial environments by potentially toxic
      metals is highlighted by the possible impacts that their high availability can
      have on the environment. Thus, the development of alternative absorbents that can
      be used in the remediation of contaminated areas is of great environmental
      interest. Humin, one of the fractions of natural organic matter, is a promising
      alternative in studies on the retention of different metals that are
      environmentally toxic. In this study, the influence of the organic and inorganic
      humin constituents that are involved in the retention of aluminum species was
      evaluated. After extraction and calcination to obtain the ashes (inorganic
      constituents), humin and ash samples were structurally characterized by Fourier
      transform infrared spectroscopy and scanning electron microscopy. Interaction
      studies between aluminum-humin and ash-humin were performed in the pH range of
      4.0-8.0 and with various contact times. The results of the characterization of
      humin and ash showed different functional groups present in the structures of
      these materials. Based on the results of the interaction between humin-aluminum
      and ash-aluminum, it can be inferred that both the organic and inorganic
      components of humin are efficient at absorbing aluminum. However, the adsorption
      isotherms showed that humin and the ashes have different adsorption behaviors.
      Humin is the only fraction of natural organic matter with a significant inorganic
      constituent content; it is the fraction least used by researchers in this field
      and is often discarded as waste. In light of this, the results obtained in this
      work highlight the importance of humin as a natural adsorbent material. Humin may
      be promising for the removal of aluminum species in contaminated environments due
      to the presence of organic and inorganic constituents.

PMID- 29567557
TI  - Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in
      advanced NSCLC.
AB  - BACKGROUND: Lung cancer is the most common cause of cancer-related death among
      males and the second leading cause among females globally. Checkpoint inhibitors
      re-engage the immune system to fight cancer. This review evaluates phase III data
      on the use of checkpoint inhibitors in the treatment of advanced NSCLC and
      addresses PD-L1 expression in predicting efficacy. METHODS: Six phase III
      clinical trials investigating checkpoint inhibitors for NSCLC were identified
      through a search of PubMed (to November 15, 2016) and conference databases, with
      findings updated from a directed search of eligible studies conducted in January
      2018. RESULTS: Significant reductions in the risk of death ranging from 27% to
      41% and were observed second-line and beyond. A relationship between PD-L1
      expression and survival was apparent in most trials with optimal benefit for the
      highest expression levels (>=50%). Benefit was also observed at low or no PD-L1
      expression levels and in third-line in some studies. Significantly improved PFS
      was observed for pembrolizumab at high PD-L1 expression levels (>=50%) first
      line. Immune-related adverse events associated with checkpoint inhibitors are
      tolerable and rates of pneumonitis may be lower among PD-L1 inhibitors. Use of
      checkpoint inhibitors for tumors with driver mutations should only be considered
      after all appropriate targeted therapy and chemotherapy have been exhausted. PD
      L1 testing presents a valuable tool to guide treatment sequencing and we
      recommend use of agent-specific PD-L1 tests and respective scoring systems until
      a standardized, convenient and broadly applicable test is identified.
      CONCLUSIONS: Checkpoint inhibitors represent a major advance in the treatment of
      advanced NSCLC and PD-L1 status can inform treatment decisions.

PMID- 29567558
TI  - Peer support systems and professional identity of student nurses undertaking a UK
      learning disability nursing programme.
AB  - This practitioner based action research examines the implementation of the peer
      assisted study scheme (PASS) and individual peer mentoring in a cohort of first
      year undergraduate nursing students. It arose out of the desire of a small number
      of students in one UK university to transfer from the learning (intellectual)
      disabilities nursing field to other fields. The number of learning disabilities
      nurses is falling in England, and nursing shortages and student nurse retention
      generally is an international concern. The peer support was evaluated by 21
      completed questionnaires. All the students had found the sessions they attended
      useful. Four themes emerged from the study. Students reported gains in knowledge
      around academic skills, placements and their chosen field of nursing; students
      felt more confident as a result of attending the sessions; students felt
      supported, and the importance of the peer mentor's interpersonal skills was
      highlighted; and finally students had valued meeting other students in their
      chosen field. These findings are discussed with reference to relevant literature.

PMID- 29567559
TI  - Clinical practices to promote sleep in the ICU: A multinational survey.
AB  - PURPOSE: To describe sleep assessment and strategies to promote sleep in adult
      ICUs in ten countries. METHODS: Multicenter, self-administered survey sent to
      nurse managers. RESULTS: Response rate was 66% with 522 ICUs providing data.
      'Lying quietly with closed eyes' was the characteristic most frequently perceived
      as indicative of sleep by >60% of responding ICUs in all countries except Italy.
      Few ICUs (9%) had a protocol for sleep management or used sleep questionnaires
      (1%). Compared to ICUs in Northern Europe, those in central Europe were more
      likely to have a sleep promoting protocol (p < 0.001), and to want to implement a
      protocol (p < 0.001). In >80% of responding ICUs, the most common non
      pharmacological sleep-promoting interventions were reducing ICU staff noise,
      light, and nurse interventions at night; only 18% used earplugs frequently.
      Approximately 50% of ICUs reported sleep medication selection and assessment of
      effect were performed by physicians and nurses collaboratively. A multivariable
      model identified perceived nursing influence on sleep decision-making was
      associated with asking patients or family about sleep preferences (p = 0.004).
      CONCLUSIONS: We found variation in sleep promotion interventions across European
      regions with few ICUs using sleep assessment questionnaires or sleep promoting
      protocols. However, many ICUs perceive implementation of sleep protocols
      important, particularly those in central Europe.

PMID- 29567560
TI  - Classification of trace elements in tissues from organic and conventional French
      pig production.
AB  - This study assesses the impact of the farming system on the levels of copper,
      zinc, arsenic, cadmium, lead and mercury in pig tissues from three types of
      production (Organic (n = 28), Label Rouge (n = 12) and Conventional (n = 30))
      randomly sampled in different slaughterhouses. All the concentrations were below
      regulatory limits. In muscles, Cu, Zn and As were measured at slightly higher
      levels in organic samples but no differences between organic and Label Rouge was
      observed. Livers from conventional and Label Rouge pig farms exhibited higher Zn
      and Cd contents than the organic ones, probably due to different practice in zinc
      or phytase supplementation of fattening diets. Principal component analysis
      indicated a correlation between Cu and As concentrations in liver and carcass
      weight, and between Zn and Cd liver levels and lean meat percentage. The linear
      discriminant analysis succeeded in predicting the farming process on the basis of
      the lean meat percentage and the liver Cd level.

PMID- 29567561
TI  - Medical image analysis of knee joint lipoma arborescens and arthroscopic
      treatment.
AB  - OBJECTIVE: Arthroscopy is a minimally invasive surgical procedure on a joint in
      which examination and treatment of knee damage is performed using a surgical
      device known as the arthroscope. Lipoma arborescens (LA), an infrequent intra
      articular lesion, originates from mature adipose cells under subsynovial tissue.
      The synovial membrane is pale yellow with large villous projections. It is caused
      by various underlying factors. We found many patients with LA and processed them
      appropriately.The research was implemented to investigate therapeutic effect of
      semi-automated arthroscopic diagnosis and treatment for knee joint. METHODS: We
      used the Stryker arthroscopic in surgery that is 4 mm in diameter with angle at
      30 degrees . Patients were chosen by biomechanical analysis and scanning mode.
      All of the patients underwent radiographic imaging examination, Magnetic
      Resonance Imaging (MRI), Lysholm Score and Visual Analogue Scale (VAS).
      Arthroscopic limited synovectomy was carried out on these patients. RESULTS: The
      wound of all patients healed up. The content of follow-up includes: chief
      complaints, range of motion of knee joint, Visual Analogue Scale (VAS) and
      Lysholm score. No swollen nor effusion of the infected knee was found in all
      patients during the follow-up. The postoperative symptom was markedly alleviated
      in fourteen patients and partially alleviated in one. All patients were satisfied
      with the therapeutic effect. CONCLUSION: We performed biomechanical analysis
      based on knee slight flexion and extension. Arthroscopy is an endoscope for the
      diagnosis and treatment of joint diseases. Semi-automated arthroscopic
      debridement is good for early and mid-term osteoarthritis with Lipoma
      arborescens.

PMID- 29567562
TI  - Learning how to use a tool: Mutually exclusive tool-function mappings are
      selectively acquired from linguistic in-group models.
AB  - The current study investigated whether 4-year-olds used language as a cue to
      social group membership to infer whether the tool-use behavior of a model needed
      to be encoded as indicative of the tool's function. We built on children's
      tendency to treat functions as mutually exclusive, that is, their propensity to
      refrain from using the same tool for more than one function. We hypothesized that
      children would form mutually exclusive tool-function mappings only if the source
      of the function information was a linguistic in-group person (native) as opposed
      to an out-group (foreign) person. In Experiment 1, participants (N = 39) were
      presented with four tool-function pairs by a model who had previously spoken
      either in their native language or in a foreign language. During the test phase,
      children encountered new purposes for which they could either use the
      demonstrated tools' color variant or use another equally suitable, as yet unseen,
      alternative tool. In line with our predictions, children preferred to use the
      alternative tool for the new function only in the native language condition
      (native: 63.3%; foreign: 42.7%). Experiment 2 replicated the initial finding
      using another foreign language and demonstrated that the lack of mutually
      exclusive tool choice in the foreign condition did not originate from children's
      failure to encode the demonstration. These findings suggest that children
      restrict learning artifact functions from linguistic in-group models. The mutual
      exclusivity principle in the domain of function learning is used more flexibly
      than previously proposed.

PMID- 29567563
TI  - TET-2 up-regulation is associated with the anti-inflammatory action of Vicenin-2.
AB  - Vicenin-2, a C-glycoside flavone that is present in many plant sources, exerts
      potent anti-inflammatory effects in a number of cell and animal models of
      inflammation. Ten-eleven translocation (TET)-2 has recently gained considerable
      attention due to the role it plays in regulating the inflammasome. We studied the
      ability of Vicenin-2 (V-2) to regulate a range of lipopolysaccharide (LPS)
      stimulated inflammatory activities in PMA-differentiated THP-1 cells and human
      primary mononuclear cells. We also investigated the action of V-2 on the
      secretion of NLRP3 inflammasome regulated cytokines (IL-1beta and IL-18) by
      ELISA, and determined if V-2 can regulate the expression of NLRP3, IL-10, IL-1Ra
      and TET-2. The effect of V-2 on NF-kappaB signalling was investigated by
      fluorescence microscopy and gene reporter assay. Additionally, the effect of V-2
      on LPS-induced phosphorylation of IKB-alpha was also investigated by Western blot
      analysis. V-2 down-regulated LPS-induced secretion of proinflammatory cytokines
      (TNF-alpha and IL-1beta), in both THP-1 and primary mononuclear cells. V-2 also
      decreased the LPS-stimulated secretion of IL-18 in THP-1 cells. V-2 significantly
      down-regulated TNF-alpha induced NF-kappaB reporter activity in HEK293T
      transfected cells and attenuated IKB-alpha phosphorylation in THP-1 cells. V-2
      treatment also induced enhanced nuclear staining of the p50 subunit and reduced
      p65 subunit of NF-kappaB. V-2 treatment alone increased the expression of anti
      inflammatory cytokine, IL-10, and the regulator of the inflammasome; IL-1Ra, in
      the presence of LPS. V-2 also significantly decreased LPS-induced NLRP3
      expression while concomitantly increasing TET-2 expression. This study
      demonstrates that the anti-inflammatory actions of V-2 are associated not only
      with increased IL-10 and IL-1Ra expression, but also with TET-2 up-regulation.
      Further work is required to establish if the effects of V-2 can be definitively
      linked to TET-2 activity and that these actions are mirrored in a range of
      relevant cell types.

PMID- 29567564
TI  - Simultaneous detection of gastric cancer-involved miR-106a and let-7a through a
      dual-signal-marked electrochemical nanobiosensor.
AB  - miRNAs are among the novel biomarkers that can be evaluated for sensitive and
      early cancer diagnosis. In the present study, an electrochemical nanobiosensor
      has been fabricated to detect two gastric cancer (GC) related miRNAs
      simultaneously. By employing Au nanoparticles- and CdSe@CdS quantum dots
      contained magnetic nanocomposites as electrochemical labels along with the
      polythiophene/reduced graphene oxide-modified carbon electrodes, this dual signal
      nanobiosensor showed a considerable performance in quantifying miR-106a (a GC
      oncogenic miRNA) and let-7a (a GC tumor suppressor miRNA). Using cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV), not only the
      accomplishment of desired biosensing platform construction was confirmed, but
      also its great specificity, appropriate selectivity, acceptable stability, and
      significant sensitivity were indicated. Through the combined analyses of the dual
      miRNAs, our nanobiosensor reached detection limit of 0.02 fM and 0.06 fM for let
      7a and miR-106a, respectively. This multiplex PCR-free miRNA nanobiosensor
      demonstrates attractive potentials for promising applications in early diagnosis
      of GC and additionally the screen of any miRNA sequence.

PMID- 29567565
TI  - Silver decahedral nanoparticles empowered SPR imaging-SELEX for high throughput
      screening of aptamers with real-time assessment.
AB  - A highly efficient method for aptamer screening with real-time monitoring of the
      SELEX process was described by silver decahedra nanoparticles (Ag10-NPs) enhanced
      surface plasmon resonance imaging (SPRI). A microarray chip was developed by
      immobilization of target protein (Lactoferrin (Lac)) and control proteins (alpha
      lactalbumin (alpha), beta-lactoglobulin (beta), casein, and bovine serum albumin
      (BSA)) on the biochip surface. Ag10-NPs were conjugated with an ssDNA library
      (lib) (Ag10-NPs-library) that consisted of a central 40 nt randomized sequence
      and a 20 nt fixed primer sequence. Introduction of the Ag10-NPs-library to the
      SPRI flow channels drastically increased the sensitivity of SPRI signal for real
      time monitoring of SELEX. The work allows rapid screening of potential targets,
      and yields nine aptamers with high affinity (nanomolar range) for Lac after only
      six-rounds of selection. The aptamer Lac 13-26 was then further tested by SPRI,
      and the results demonstrated that the aptamer had the capacity to be ultra
      sensitive for specific detection of Lac. The novel SPRI-SELEX method demonstrated
      here showed many advantages of real-time evaluation, high throughput, and high
      efficiency.

PMID- 29567566
TI  - Wirelessly powered and remotely controlled valve-array for highly multiplexed
      analytical assay automation on a centrifugal microfluidic platform.
AB  - In this paper we present a wirelessly powered array of 128 centrifugo-pneumatic
      valves that can be thermally actuated on demand during spinning. The valves can
      either be triggered by a predefined protocol, wireless signal transmission via
      Bluetooth, or in response to a sensor monitoring a parameter like the
      temperature, or homogeneity of the dispersion. Upon activation of a resistive
      heater, a low-melting membrane (ParafilmTM) is removed to vent an entrapped gas
      pocket, thus letting the incoming liquid wet an intermediate dissolvable film and
      thereby open the valve. The proposed system allows up to 12 heaters to be
      activated in parallel, with a response time below 3 s, potentially resulting in
      128 actuated valves in under 30 s. We demonstrate, with three examples of common
      and standard procedures, how the proposed technology could become a powerful tool
      for implementing diagnostic assays on Lab-on-a-Disc. First, we implement wireless
      actuation of 64 valves during rotation in a freely programmable sequence, or upon
      user input in real time. Then, we show a closed-loop centrifugal flow control
      sequence for which the state of mixing of reagents, evaluated from
      stroboscopically recorded images, triggers the opening of the valves. In our last
      experiment, valving and closed-loop control are used to facilitate centrifugal
      processing of whole blood.

PMID- 29567567
TI  - Molecularly imprinted sensor based on Russian Matryoshka structured molecules for
      enhanced specific identification and double amplification in ultra-trace Tb3+
      determination.
AB  - The selective and sensitive detection of rare earth elements is thought to be
      difficult because the concentration of those elements in the sample is commonly
      at a low level and they normally have severe mutual interference which is caused
      by homologous chemical properties. In this study, a novel molecularly imprinted
      polymer (MIP) sensor was fabricated for highly sensitive and selective
      determination of ultra-trace Tb3+. The Tb3+-ethylenediaminetetraacetic acid
      complex (Tb-EDTA) as the template molecule was incorporated into mono-6-mercapto
      beta-cyclodextrin (mono-6-SH-beta-CD) to form a Russian Matryoshka (RM)
      structured molecule (CD/Tb-EDTA). Titanium isopropoxide was utilized in vapor sol
      gel polymerization to construct MIP membrane. Moreover, the selectivity of the RM
      MIP sensor was remarkably enhanced by the "triple-selectivity" recognition of
      EDTA-to-Tb3+, beta-CD-to-(Tb-EDTA), and 3D cavity-to-(CD/Tb-EDTA), while the
      sensitivity of the MIP sensor was significantly improved by ECL signal
      enhancement based on double amplification, in other words, the
      electrochemiluminescence resonance energy transfer (ECL-RET) between the ECL
      donor of CD/Tb-EDTA and the ECL acceptor of Ru(bpy)32+, and the ECL enhancement
      by the co-reactant of CD/Tb-EDTA on Ru(bpy)3Cl2. When the imprinted cavities were
      occupied by Tb-EDTA during rebinding, the host-guest inclusion structured complex
      was formed and the ECL intensities produced by the Ru(bpy)3Cl2 ECL system
      increased with increasing concentration of Tb-EDTA. The proposed sensor was used
      for quantitative analysis of Tb3+ with concentrations ranging from 8.00 * 10-13
      mol/L to 4.00 * 10-9 mol/L and successfully applied to detect Tb3+ in seawater
      samples. The detection limit of the sensor was found to be 3.90 * 10-13 mol/L (DL
      = 3deltab/K), which is lower than previously reported values. Thus, the
      fabricated sensor is feasible for practical applications.

PMID- 29567568
TI  - Hybridization conditions of oligonucleotide-capped gold nanoparticles for SPR
      sensing of microRNA.
AB  - MicroRNA (miRNA) sensing, especially the miRNA-200 family, is increasingly
      targeted for cancer diagnostics. As the sensing schemes often rely on
      nanoparticles functionalized with a specific oligonucleotide, we investigate the
      hydribization conditions using the common case of surface plasmon resonance (SPR)
      sensing of miRNA and a gold nanoparticle (Au NP) competitor. In this type of
      assays, the Au NPs compete with the microRNA to bind the capture probe
      immobilized on the gold surface. In our study, we simplify and improve the
      detection procedure by adopting 11-mercaptoundecanoic acid (11-MUA) as linker to
      the gold surface, not only omitting the blocking step of 6-mercapto-1-hexanol
      (MCH), but also increasing the probe density. We report that the response in our
      SPR sensing studies increased with the size of Au NPs according to the plasmon
      ruler equation, but the larger AuNPs of 32 nm lacked colloidal stability. In
      addition, decreasing the ratio of oligonucleotide to Au NPs and the addition of
      polyethylene glycol (PEG) to hybridization buffer also favored a better response
      in SPR sensing of miRNA. The optimization led to an improved detection
      sensitivity in our competition method and a detection limit as low as 500 pM for
      miRNA-200b without amplification of miRNA and use of other amplification schemes.

PMID- 29567569
TI  - Ipsilateral stress fracture of the proximal fibula after total knee arthroplasty
      in a patient with severe valgus knee deformity on a background of Rheumatoid
      arthritis.
AB  - INTRODUCTION: Previous studies have reported a lower extremity stress fracture
      after total knee arthroplasty (TKA). However, a fibular fracture after TKA is
      quite rare. We report a case of proximal fibula fracture after TKA in a patient
      with rheumatoid arthritis (RA). PRESENTATION OF CASE: A 45 year old woman with RA
      had severe knee and foot pain with an antalgic gait disturbance. There was a
      significant joint deformity in many of lower limb joints. Interval bilateral TKAs
      were performed two weeks apart. Right TKA was performed using a constraint-type
      prosthesis, through lateral parapatellar approach. Left TKA was performed using a
      posterior-stabilized (PS) prosthesis through the more commonly employed, medial
      parapatellar approach. Seven weeks after the right TKA, the patient was found to
      have an atraumatic proximal fibular fracture. The fracture went on to heal
      conservatively. DISCUSSION: The fracture was considered to have occurred after
      the TKA. The callus appeared eleven weeks after the TKA. The factors that
      contributed to the fracture were thought to be overload of the fragile bone
      secondarily to disuse osteopaenia, RA or potentially the significant valgus
      malalignment correction. The surgical approach, the implant or implantation or
      the persisting joint deformity, were thought to be contributing factors to the
      aetiology of the stress fracture. The resultant change in clinical outcome/course
      is outlined in this case report. CONCLUSION: A stress fracture of the proximal
      fibula has the potential in the aetiology of may cause other stress fractures,
      joint other instability, and/or malalignment of the total lower extremity.

PMID- 29567570
TI  - Coating process optimization through in-line monitoring for coating weight gain
      using Raman spectroscopy and design of experiments.
AB  - In this study the authors developed a real-time Process Analytical Technology
      (PAT) of a coating process by applying in-line Raman spectroscopy to evaluate the
      coating weight gain, which is a quantitative analysis of the film coating layer.
      The wide area illumination (WAI) Raman probe was connected to the pan coater for
      real-time monitoring of changes in the weight gain of coating layers. Under the
      proposed in-line Raman scheme, a non-contact, non-destructive analysis was
      performed using WAI Raman probes with a spot size of 6 mm. The in-line Raman
      probe maintained a focal length of 250 mm, and a compressed air line was designed
      to protect the lens surface from spray droplets. The Design of Experiment (DOE)
      was applied to identify factors affecting the Raman spectra background of laser
      irradiation. The factors selected for DOE were the strength of compressed air
      connected to the probe, and the shielding of light by the transparent door
      connecting the probe to the pan coater. To develop a quantitative model, partial
      least squares (PLS) models as multivariate calibration were developed based on
      the three regions showing the specificity of TiO2 individually or in combination.
      For the three single peaks (636 cm-1, 512 cm-1, 398 cm-1), least squares method
      (LSM) was applied to develop three univariate quantitative analysis models. One
      of best multivariate quantitative model having a factor of 1 gave the lowest
      RMSEP of 0.128, 0.129, and 0.125, respectively for prediction batches. When LSM
      was applied to the single peak at 636 cm-1, the univariate quantitative model
      with an R2 of 0.9863, slope of 0.5851, and y-intercept of 0.8066 had the lowest
      RMSEP of 0.138, 0.144, and 0.153, respectively for prediction batches. The in
      line Raman spectroscopic method for the analysis of coating weight gain was
      verified by considering system suitability and parameters such as specificity,
      range, linearity, accuracy, and precision in accordance with ICH Q2 regarding
      method validation. The proposed in-line Raman spectroscopy can be utilized as a
      PAT for product quality assurance as it offers real-time monitoring of
      quantitative changes in coating weight gain and process end-points during the
      film coating process.

PMID- 29567571
TI  - Development of a HILIC method for the determination of 5-fluorouracil from nano
      drug delivery systems and rat skin extracts.
AB  - This is the first report in literature using hydrophilic interaction liquid
      chromatography (HILIC) in combination with diode array detector (DAD) for
      stability indicating determination of 5-Fluorouracil (5-FU) from its bulk form,
      pharmaceutical preparations, developed solid lipid nanoparticle (SLN) and nano
      structured lipid carrier (NLC) drug delivery systems as well as the rat skin
      extracts. The separation was performed at 45  degrees C, on Sequant Zic HILIC
      (250 mm * 4.60 mm ID, 5 MUm, 200 Ao), peek HPLC column. Mobile phase is
      consisting of a mixture of acetonitrile: buffer containing 5 mM ammonium acetate
      (95:5; v/v). The pH of the mobile phase was adjusted to 7.0 using 1 M NaOH. The
      analysis was carried out at 0.75 mL min-1 flow rate with a detection wavelength
      of 265 nm and the injection volume was arranged as 10 MUL. The developed method
      was fully validated in accordance with the International Council on Harmonization
      (ICH) Guidelines. Specificity of this method was demonstrated by forced
      degradation studies. As a result of calibration studies, the calibration curve
      was found linear in the concentration range of 1-250 MUg mL-1 (R2 = 0.999). The
      precision of this technique calculated within the frame of intra-day and inter
      day based on a percentage of relative standard deviation (RSD%) values (<2%). The
      limits of detection and quantification were 11 and 37 ng mL-1 respectively. On
      the other hand, 5-FU loaded SLN and NLC formulations with average particle size
      of 370 nm were also developed and compared in order to increase the permeation of
      drug into the rat skin. Ex-vivo Penetration/Permeation Studies indicated that
      higher dermal accumulation of 5-FU was obtained with NLC formulation. As a
      conclusion, the present work expressed the optimization and the validation of a
      selective, simple, precise and accurate fully validated HILIC method with
      sufficient sensitivity for the estimation of 5-FU in raw materials, marketed
      formulation and rat skin extract after applying both of the commercial product
      and newly developed nanoparticulate drug delivery systems on to the rat skins
      with high percentage recoveries.

PMID- 29567572
TI  - Unveiling anticancer potential of glibenclamide: Its synergistic cytotoxicity
      with doxorubicin on cancer cells.
AB  - Drug repurposing has been an emerging therapeutic strategy, which involves
      exploration of a new therapeutic approach for the use of an existing drug.
      Glibenclamide (Gli) is an anti-diabetic sulfonylurea drug extensively used for
      the treatment of type-2 diabetes, it has also been shown to possess anti
      proliferative effect against several types of tumors. The present study was
      executed to understand the mechanisms underlying the interaction of Gli with DNA
      under physiological conditions. The binding mechanism of Gli with DNA was
      scrutinized by UV-vis absorption spectroscopy and fluorescence emission
      spectroscopy. The conformational changes and electrochemical properties were
      analyzed by circular dichroism spectroscopy and cyclic voltammetry. Isothermal
      titration calorimetry was employed to examine the thermodynamic changes and
      molecular docking technique used to analyze the interaction mode of Gli with DNA.
      The spectroscopic studies revealed that Gli interacts with DNA through groove
      binding mode. Further, isothermal titration calorimetry depicted a stronger mode
      of interaction favorably groove-binding. Recently, systemic combination therapy
      has shown significant promise in inhibiting multiple targets simultaneously
      yielding high therapeutic competence with lesser side effects. With this concern,
      we intended to study the combined cytotoxicity of Gli with doxorubicin (Dox). The
      results of MTT assay and acridine orange (AO)/ethidium bromide (EtBr) staining
      showed synergistic cytotoxicity of Gli + Dox combination on HepG2 & A549 cells.
      The present study documents the intricate mechanism of Gli-DNA interaction and
      delivers a multifaceted access for chemotherapy by Gli + Dox combination.

PMID- 29567573
TI  - 1H NMR-based metabolomics approach to investigate the urine samples of collagen
      induced arthritis rats and the intervention of tetrandrine.
AB  - Tetrandrine is an effective ingredient isolated from the roots of a frequently
      used medicinal plant Stephania tetrandra S. Moore. It has been used for the
      management of arthritis in China, but the precise mechanism remains unclear. In
      the present study, a metabolomics method based on the 1H NMR was constituted to
      quantify the alterations of the endogenous metabolites in the urines of collagen
      induced arthritis (CIA) rats treated with tetrandrine. Data showed that
      tetrandrine treatment could alleviate the ankle joint swelling and ameliorate
      histopathological changes in rats. The metabonomic analysis indicated that 23
      potential biomarkers in urine were affiliated with CIA. They mainly participated
      in energy metabolism, amino acid metabolism, lipid metabolism and gut microbe
      metabolism. Moreover, our results implied that tetrandrine could reverse the
      pathological process of CIA through adjusting the unbalanced metabolic pathways.
      Thus, these metabolic pathways and potential biomarkers might be the potential
      therapeutic targets of tetrandrine, and these findings supplied new visions into
      the protective effect of tetrandrine against arthritis in rats.

PMID- 29567574
TI  - Fast identification of anticancer constituents in Forsythiae Fructus based on
      metabolomics approaches.
AB  - An herb commonly contains hundreds of constituents. Identification of bioactive
      compound(s) in each herb using conventional approaches is usually inefficient and
      eco-unfriendly. In this study, we aimed to fast identify anticancer compounds in
      Forsythiae Fructus using UPLC/MS-based metabolomics analysis. We firstly
      fractionated Forsythiae Fructus crude extracts with organic solvents of different
      polarity, then the chemical profile of each fraction was analyzed by UPLC/Q
      TOF/MS, and the anticancer activity profiles of all fractions were determined by
      MTT assay. Next, orthogonal projections to latent structures discriminant
      analysis (OPLS-DA) was applied to discriminate fractions with different
      anticancer activity to determine the compound(s) that contributes most to the
      anticancer activity. Betulinic acid was then identified to be the most potent
      anticancer compound in Forsythiae Fructus. Its predicted anticancer activity was
      confirmed by MTT assay. Taken together, our results demonstrated that the present
      integrated metabolomics strategy could be used for fast identification of
      anticancer compound(s) in herb extracts or other complex mixtures of chemicals.

PMID- 29567575
TI  - Comparative studies on the human serum albumin binding of the clinically approved
      EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the
      investigational inhibitor KP2187.
AB  - Binding interactions between human serum albumin (HSA) and four approved
      epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib
      (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug
      KP2187, were investigated by means of spectrofluorometric and molecular modelling
      methods. Steady-state and time resolved spectrofluorometric techniques were
      carried out, including direct quenching of protein fluorescence and site marker
      displacement measurements. Proton dissociation processes and solvent dependent
      fluorescence properties were investigated as well. The EGFR inhibitors were
      predominantly presented in their single protonated form (HL+) at physiological pH
      except ERL, which is charge-neutral. Significant solvent dependent fluorescence
      properties were found for GEF, ERL and KP2187, namely their emission spectra show
      strong dependence on the polarity and the hydrogen bonding ability of the
      solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA)
      in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI
      (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA),
      while GEF, ERL and AFA clearly show no interaction here. Docking methods
      qualitatively confirmed binding site preferences of compounds GEF and KP2187, and
      indicated that they probably bind to HSA in their neutral forms. Binding
      constants calculated on the basis of the various experimental data indicate a
      weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity
      towards this protein. However, model calculations performed at physiological
      blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the
      inhibitors, highlighting the importance of plasma protein binding.

PMID- 29567576
TI  - The human natural killer-1 (HNK-1) glycan mimetic ursolic acid promotes
      functional recovery after spinal cord injury in mouse.
AB  - Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in
      several neural events, such as neuritogenesis, myelination, synaptic plasticity
      and regeneration of the nervous system after injury. We have recently identified
      the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to
      test its therapeutic potential in the central nervous system. UA, a plant-derived
      pentacyclic triterpenoid, is well known for its multiple biological functions,
      including neuroprotective, antioxidant and anti-inflammatory activities. In the
      present study, we evaluated its functions in a mouse model of spinal cord injury
      (SCI) and explored the molecular mechanisms underlying its positive effects. Oral
      administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks
      enhanced the regaining of motor functions and axonal regrowth, and decreased
      astrogliosis. UA administration decreased levels of proinflammatory markers,
      including interleukin-6 and tumor necrosis factor-alpha, in the injured spinal
      cord at the acute phase of inflammation and activated the mitogen-activated
      protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of
      rapamycin pathways in the injured spinal cord. Taken together, these results
      suggest that UA may be a candidate for treatment of nervous system injuries.

PMID- 29567577
TI  - Development of atherosclerotic-moyamoya syndrome with genetic variant of RNF213
      p.R4810K and p.T1727M: A case report.
AB  - OBJECTIVE: We report a rare case of atherosclerotic-moyamoya syndrome (A-MMS) in
      an adult female with genetic variant of both ring finger 213 (RNF213) p.R4810K
      and p.T1727M. CASE REPORT: A 46-year-old previously healthy, right-handed woman
      displayed transient slurred speech, which started to worsen four years ago.
      Initial magnetic resonance angiography (MRA) revealed stenosis in left middle
      cerebral artery (MCA), bilateral anterior cerebral artery (ACA), and left
      posterior cerebral artery (PCA). The patient subsequently underwent catheter
      angiography, which confirmed the formation of moyamoya vessels, with Suzuki's
      angiographic staging of grade-3 on the left side. Although the patient had been
      on both anti-platelet and statin therapy at the time, a follow-up examination
      showed further exacerbation of left MCA stenosis, along with enhanced moyamoya
      vessel formation. On black-blood imaging using DANTE-SPACE, there were eccentric,
      evolving lesions in the left MCA. We next screened for potential genetic
      variants, using genomic DNA samples isolated from both the patient and her
      immediate family members. The results showed that the patient, along with her
      mother, sister, and brother, possessed the heterozygous variant of the RNF213
      gene, including c.14429G > A (p.R4810K) and c.5180C > T (p.T1727M). The patient's
      daughter did not have the variant. CONCLUSION: Collectively, we present a unique
      case of A-MMS with genetic variant of RNF213 p.R4810K and p.T1727M, manifesting
      as progression. Based on the family tree, these two mutations are on the same
      RNF213 haplotype. Whether atherosclerosis is the cause of A-MMS or it further
      exacerbates the injury of MMD to the A-MMS patients with RNF213 gene variant is a
      question to be investigated.

PMID- 29567578
TI  - Correlation and clinical significance of LC3, CD68+ microglia, CD4+ T
      lymphocytes, and CD8+ T lymphocytes in gliomas.
AB  - OBJECTIVE: To investigate the relationship between the expression of microtubule
      associated protein LC3 and the numbers of CD68 + microglia, CD4 + T lymphocytes
      and CD8 + T lymphocytes, as well as the clinical significance of those factors in
      gliomas. PATIENTS AND METHODS: The study group consisted of 127 patients with
      gliomas who were operated to our hospital, we examined the expression of LC3 by
      Immunohistochemistry and Western blot, and we assessed the numbers of CD68 +
      microglia, CD4 + T lymphocytes and CD8 + T lymphocytes by Immunohistochemistry,
      we analyze the relationship between all the factors and explore the significance.
      RESULTS: Immunohistochemistry and Western blotting showed that the expression of
      LC3 in normal brain tissue, low-grade gliomas, and high-grade gliomas are
      elevated to varying degrees (P < 0.01); Immunohistochemical detection showed that
      the numbers of CD68 + microglia, CD4 + T lymphocytes and CD8 + T lymphocytes in
      gliomas was higher than that in normal brain tissues (P < 0.01), and the high
      grade gliomas were higher than those in low-grade gliomas (P < 0.01); The results
      of Spearman correlation showed that the expression of LC3 was positively
      correlated with the numbers of CD68 + microglia, CD4 + T lymphocytes, and CD8 + T
      lymphocytes (P < 0.05); Furthermore, survival analysis showed that LC3, CD68 +
      microglia, CD8 + T lymphocytes and tumor grade were independent prognostic
      factors of glioma. CONCLUSIONS: LC3 may be one of the factors that affect the
      tumor cellular immunity response in gliomas. The simultaneous detection of LC3,
      CD68 + microglia and CD8 + T lymphocytes can be used to assess the prognosis of
      glioma.

PMID- 29567579
TI  - Palliative shunt surgery for patients with leptomeningeal metastasis.
AB  - OBJECTIVES: Leptomeningeal metastasis (LM) is associated with poor prognosis and
      affects the quality of life (QOL) of end-stage cancer patients. Severe headache
      associated with hydrocephalus causes reduced QOL. We investigated the clinical
      value of surgical treatment for hydrocephalus in LM patients. PATIENTS AND
      METHODS: The medical records of 11 consecutive patients who underwent
      lumboperitoneal shunt (LPS) or ventriculoperitoneal shunt (VPS) at our
      institution between 2007 and 2016 were investigated. Primary brain tumor patients
      were excluded. We assessed the neurological status and therapeutic effects at 1
      month after the shunt surgery. RESULTS: The patients were three males and eight
      females with a median age of 58 years (interquartile range [IR] 52-68 years). The
      median preoperative neutrophil-to-lymphocyte ratio was 6.4 (IR 4.8-9.2). Symptom
      improvement was observed in nine patients, and severe headache was relieved in
      seven (88%) out of eight patients. The median Karnofsky performance status scale
      increased from 40 to 60, and the median overall survival after primary malignancy
      diagnosis was 27.4 months (IR 19.6-63.1 months). The median survival after the
      diagnosis of brain parenchymal metastasis, LM, and shunt surgery were 7.2 months
      (IR 5.1-14.1 months), 3.9 months (IR 3.5-6.3 months), and 3.3 months (IR 2.9-5.7
      months), respectively. CONCLUSION: Shunt surgery for hydrocephalus could offer an
      effective palliative surgical option for symptom relief especially relief of
      severe headache, contributing improvement of QOL in LM patients.

PMID- 29567580
TI  - Nano-spectroscopic imaging of proteins with near-field scanning optical
      microscopy (NSOM).
AB  - Understanding the hierarchical structure of proteins at their fundamental length
      scales is essential to get insights into their functions and roles in fundamental
      biological processes. Near-field scanning optical microscopy (NSOM), which
      overcomes the diffraction limits of conventional optics, provides a powerful
      analytical tool to image target proteins at nanoscale resolution. Especially, by
      combining NSOM with infrared (IR) or Raman spectroscopy, near-field
      nanospectroscopic imaging of a single protein is achieved. In this review, we
      present the recent technical progress of NSOM setup for nanospectroscopic imaging
      of proteins, and its application to nanospectroscopic analysis of protein
      structures is highlighted and critically reviewed. Finally, current challenges
      and perspectives on application of NSOM in emerging areas of industrial,
      environmental and medical biotechnology are discussed.

PMID- 29567581
TI  - Metabolomics tools for the synthetic biology of natural products.
AB  - Metabolomics plays an increasingly central role within the Design-Build-Test
      cycle of synthetic biology, in particular in applications targeting the
      discovery, diversification and optimised production of a wide range of natural
      products. For example, improved methods for the online monitoring of chemical
      reactions accelerate data generation to be compatible with the rapid iterations
      and increasing library sizes of automated synthetic biology pipelines.
      Combinations of label-free metabolic profiling and 13C-based flux analysis lead
      to increased resolution in the identification of metabolic bottlenecks affecting
      product yield in engineered microbes. And molecular networking strategies
      drastically increase our ability to identify and characterise novel chemically
      complex biomolecules of interest in a diverse range of samples.

PMID- 29567583
TI  - Event-related brain potentials elicited by high-speed cooling of the skin: A
      robust and non-painful method to assess the spinothalamic system in humans.
AB  - OBJECTIVE: To investigate whether cool-evoked potentials (CEP) elicited by brisk
      innocuous cooling of the skin could serve as an alternative to laser-evoked
      potentials (LEP), currently considered as the best available neurophysiological
      tool to assess the spinothalamic tract and diagnose neuropathic pain. METHODS: A
      novel device made of micro-Peltier elements and able to cool the skin at -300 
      degrees C/s was used to record CEPs elicited by stimulation of the hand dorsum in
      40 healthy individuals, characterize the elicited responses, and assess their
      signal-to-noise ratio. Various stimulation surfaces (40 mm2 and 120 mm2), cooling
      ramps (-200  degrees C/s and -133  degrees C/s) and temperature steps (20 
      degrees C, 15  degrees C, 10  degrees C, 5  degrees C) were tested to identify
      optimal stimulation conditions. RESULTS: CEPs were observed in all conditions and
      subjects, characterized by a biphasic negative-positive complex maximal at the
      vertex (Cz), peaking 190-400 ms after stimulus onset, preceded by a negative wave
      over central-parietal areas contralateral to the stimulated hand. Their magnitude
      was modulated by stimulation surface, cooling ramp and temperature step.
      CONCLUSION: Rapid innocuous skin cooling elicits robust CEPs at latencies
      compatible with the conduction velocity of Adelta-fibers. SIGNIFICANCE: CEPs can
      be a complementary tool to the recording of LEPS for assessing the function of
      small-diameter Adelta-fibers and the spinothalamic tract.

PMID- 29567582
TI  - Intra-operative characterisation of subthalamic oscillations in Parkinson's
      disease.
AB  - OBJECTIVE: This study aims to use the activities recorded directly from the deep
      brain stimulation (DBS) electrode to address the focality and distinct nature of
      the local field potential (LFP) activities of different frequency. METHODS: Pre
      operative and intra-operative magnetic resonance imaging (MRI) were acquired from
      patients with Parkinson's disease (PD) who underwent DBS in the subthalamic
      nucleus and intra-operative LFP recording at rest and during cued movements.
      Images were reconstructed and 3-D visualized using Lead-DBS(r) toolbox to
      determine the coordinates of contact. The resting spectral power and movement
      related power modulation of LFP oscillations were estimated. RESULTS: Both
      subthalamic LFP activity recorded at rest and its modulation by movement had
      focal maxima in the alpha, beta and gamma bands. The spatial distribution of
      alpha band activity and its modulation was significantly different to that in the
      beta band. Moreover, there were significant differences in the scale and timing
      of movement related modulation across the frequency bands. CONCLUSION:
      Subthalamic LFP activities within specific frequency bands can be distinguished
      by spatial topography and pattern of movement related modulation. SIGNIFICANCE:
      Assessment of the frequency, focality and pattern of movement related modulation
      of subthalamic LFPs reveals a heterogeneity of neural population activity in this
      region. This could potentially be leveraged to finesse intra-operative targeting
      and post-operative contact selection.

PMID- 29567584
TI  - Interaction between striatal volume and DAT1 polymorphism predicts working memory
      development during adolescence.
AB  - There is considerable inter-individual variability in the rate at which working
      memory (WM) develops during childhood and adolescence, but the neural and genetic
      basis for these differences are poorly understood. Dopamine-related genes,
      striatal activation and morphology have been associated with increased WM
      capacity after training. Here we tested the hypothesis that these factors would
      also explain some of the inter-individual differences in the rate of WM
      development. We measured WM performance in 487 healthy subjects twice: at age 14
      and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of
      five single nucleotide polymorphisms (SNPs) in or close to the dopamine genes
      DRD2, DAT-1 and COMT, which have previously been associated with gains in WM
      after WM training. We then analyzed which biological factors predicted the rate
      of increase in WM between ages 14 and 19. We found a significant interaction
      between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC
      heterozygotes with a larger putamen at age 14 showed greater WM improvement at
      age 19. The effect of the DAT1 polymorphism on WM development was exerted in
      interaction with striatal morphology. These results suggest that development of
      WM partially share neuro-physiological mechanism with training-induced
      plasticity.

PMID- 29567585
TI  - Paraganglioma in an explanted heart.

PMID- 29567586
TI  - Obesity and risk for venous thromboembolism from contemporary therapy for
      pediatric acute lymphoblastic leukemia.
AB  - INTRODUCTION: Acute lymphoblastic leukemia (ALL) therapy confers risk for venous
      thromboembolism (VTE) and associated acute and long-term morbidity. Obesity
      increases VTE risk in the general population but its impact on ALL therapy
      associated VTE is unknown. METHODS: In a retrospective cohort of children treated
      for ALL between 2008 and 2016 (n = 294), we analyzed obesity at diagnosis (body
      mass index [BMI] >=95%) and subsequent development of VTE. A subset participated
      in two concurrent prospective ALL trials studying body composition via dual
      energy X-ray absorptiometry (DXA) (n = 35) and hypercoagulability via
      thromboelastography (TEG) (n = 46). Secondary analyses explored whether precise
      measurement of body fat and/or global hemostasis ex vivo by TEG could further
      delineate VTE risk in the obese. RESULTS: Overall, we found 27/294 (9.2%)
      patients developed symptomatic VTE during therapy, 19/27 (70%) occurred during
      Induction. Study-defined "serious" VTE developed in 4/294 (1.4%) of patients.
      Obesity but not overweight was strongly predictive of symptomatic VTE (obesity
      odds ratio = 3.8, 95% confidence interval 1.5-9.6, p = 0.008). In the DXA subset,
      only 2/35 patients developed symptomatic VTE. However, within those prospectively
      screened during Induction, 30% (14/46) developed VTE; eight (17%) of these were
      asymptomatic and found only via screening. CONCLUSIONS: In this pediatric ALL
      cohort, obesity conferred more than a three-fold increased risk for symptomatic
      VTE. In a subgroup of patients who underwent active screening, up to a third were
      noted to have VTE (symptomatic and asymptomatic). TEG did not predict VTE.
      Additional studies are necessary to validate these findings and to further refine
      a risk-stratified approach to thrombo-prevention during ALL therapy.

PMID- 29567587
TI  - Clinical and laboratory characteristics of isolated lupus anticoagulants.

PMID- 29567588
TI  - Fluorescence imaging host pathogen interactions: fifteen years benefit of
      hindsight....
AB  - We consider in review current state-of-the-art fluorescence microscopy for
      investigating the host-pathogen interface. Our perspective is honed from years
      with literally thousands of microbiologists using the variety of imaging
      technologies available within our dedicated BSL2/BSL3 optical imaging research
      service facilities at the Institut Pasteur Paris founded from scratch in 2001.
      During fifteen years learning from the success and failures of introducing
      different fluorescence imaging technologies, methods, and technical development
      strategies we provide here a synopsis review of our experience to date and a
      synthesis of how we see the future in perspective for fluorescence imaging at the
      host-pathogen interface.

PMID- 29567589
TI  - Time-to-collision analysis of pedestrian and pedal-cycle accidents for the
      development of autonomous emergency braking systems.
AB  - The aim of this study was to describe the position of pedestrians and pedal
      cyclists relative to the striking vehicle in the 3 s before impact. This
      information is essential for the development of effective autonomous emergency
      braking systems and relevant test conditions for consumer ratings. The UK RAIDS
      OTS study provided 175 pedestrian and 127 pedal-cycle cases based on in-depth, at
      scene investigations of a representative sample of accidents in 2000-2010. Pedal
      cyclists were scattered laterally more widely than pedestrians (90% of cyclists
      within around +/-80 degrees  compared to +/-20 degrees  for pedestrians), however
      their distance from the striking vehicle in the seconds before impact was no
      greater (90% of cyclists within 42 m at 3 s compared to 50 m for pedestrians).
      This data is consistent with a greater involvement of slow moving vehicles in
      cycle accidents. The implication of the results is that AEB systems for cyclists
      require almost complete 180 degrees  side-to-side vision but do not need a longer
      distance range than for pedestrians.

PMID- 29567590
TI  - Azithromycin ameliorates OVA-induced airway remodeling in Balb/c mice via
      suppression of epithelial-to-mesenchymal transition.
AB  - Azithromycin is a potent agent that prevents airway remodeling. In this study, we
      hypothesized that azithromycin (35 mg/kg orally) alleviated airway remodeling
      through suppression of epithelial-to-mesenchymal transition (EMT) via
      downregulation of transforming growth factor-beta 1 (TGF-beta1)/receptor for
      activated C-kinase1 (RACK1)/snail in mice. An ovalbumin (OVA)-induced Balb/c mice
      airway allergic inflammatory model was used. Airway inflammation and remodeling
      were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and
      Masson staining. E-cadherin and N-cadherin (molecular markers of EMT) were
      analyzed by immunofluorescence, quantitative reverse transcriptase polymerase
      chain reaction (qRT-PCR), and western blotting; alpha-smooth muscle actin (alpha
      SMA) was evaluated using immunohistochemistry (IHC), qRT-PCR, and western
      blotting; and expression of TGF-beta1/RACK1/Snail in lungs was measured by qRT
      PCR and western blotting. Our data showed that azithromycin significantly reduced
      inflammation score, peribronchial smooth muscle layer thickness, goblet cell
      metaplasia, and deposition of collage fibers (P < 0.05), and effectively
      suppressed airway EMT (upregulated E-cadherin level, and downregulated N-cadherin
      and alpha-SMA levels) compared with the OVA group (P < 0.05). Moreover, the
      increasing mRNA and protein expressions of TGF-beta1 and RACK1 and mRNA level of
      Snail in lung tissue were all significantly decreased in azithromycin-treated
      mice (P < 0.05). Taken together, our results suggest that azithromycin has the
      greatest effects on reducing airway remodeling by inhibiting TGF
      beta1/RACK1/Snail signal and improving the EMT in airway epithelium.

PMID- 29567591
TI  - Protective effects of ginsenoside Rg1 on splenocytes and thymocytes in an aging
      rat model induced by d-galactose.
AB  - Physiological aging is associated with a range of medical problems. However, the
      treatment of aging-associated diseases and prolonging human life are vital to our
      current aging societies. Panax ginseng, a traditional Chinese medicine, has been
      shown to have anti-oxidative and anti-aging effects. In the current study, aging
      rats induced by d-galactose were administered ginsenoside Rg1, then splenocytes
      and thymocytes were extracted and changes in activity were detected. The results
      demonstrated that compared with the d-gal group, the level of advanced glycation
      end products (AGE), the ratio of splenocytes and thymocytes in G0 phase (%), and
      apoptosis (%) of splenocytes and thymocytes, the ratio (%) of SA-gal positive
      splenocytes and thymocytes, the content of reactive oxygen species (ROS) and
      malondialdehyde (MDA), the ratio of glutathione (GSH) to oxidized glutathione
      (GSSG) and senescence-associated protein expression were significantly decreased
      and the index of the spleen and thymus, the proportion of white pulp in the
      spleen, the proportion of cortex in the thymus, the content of interleukin-2 (IL
      2), interleukin-6 (IL-6), granulocyte-macrophage colony stimulating factor (GM
      CSF), tumor necrosis factor-alpha (TNF-alpha), the activities of superoxide
      dismutase (SOD), and the proliferative capacity of splenocytes and thymocytes
      were increased in the Rg1+ d-gal group. These findings demonstrated that
      ginsenoside Rg1 may antagonize spleen and thymus damage in d-galactose-induced
      aging rats by alleviating oxidative stress injury and down-regulating the
      expression of senescence-associated protein.

PMID- 29567592
TI  - Training students to detect delirium: An interprofessional pilot study.
AB  - AIM: The purpose of this paper is to report nursing student knowledge acquisition
      and attitude after completing and interprofessional simulation with medical
      students. INTRODUCTION: The IOM has challenged healthcare educators to teach
      teamwork and communication skills in interprofessional settings.
      Interprofessional simulation provides a higher fidelity experience than
      simulation in silos. Simulation may be particularly useful in helping healthcare
      workers gain the necessary skills to care for psychiatric clients. Specifically,
      healthcare providers have difficulty differentiating between dementia and
      delirium. Recognizing this deficit, an interprofessional simulation was created
      using medical students in their neurology rotation and senior nursing students.
      METHOD: Twenty-four volunteer nursing students completed a pre-survey to assess
      delirium knowledge and then completed an education module about delirium. Twelve
      of these students participated in a simulation with medicine students. Pre and
      Post Kid SIM Attitude questionnaires were completed by all students participating
      in the simulation. After the simulations were complete, all twenty-four students
      were asked to complete the post-survey regarding delirium knowledge. RESULTS:
      While delirium knowledge scores improved in both groups, the simulation group
      scored higher, but the difference did not reach significance. The simulation
      group demonstrated a statistically significant improvement in attitudes toward
      simulation, interprofessional education, and teamwork post simulation compared to
      their pre-simulation scores. CONCLUSION: Nursing students who participated in an
      interprofessional simulation developed a heightened appreciation for learning
      communication, teamwork, situational awareness, and interprofessional roles and
      responsibilities. These results support the use of interprofessional simulation
      in healthcare education.

PMID- 29567593
TI  - Student health professionals' attitudes and experience after watching "Ida's
      Diary", a first-person account of living with borderline personality disorder:
      Mixed methods study.
AB  - BACKGROUND: There is increasing interest in the use of commercial movies in
      nursing education, or "cinenurducation". There is a need for educational
      interventions which target mental health nurses' attitudes towards people with
      borderline personality disorder. OBJECTIVES: To investigate and evaluate the
      experience and effects of attendance at a screening of the movie Ida's Diary, a
      first-person account of living with borderline personality disorder. DESIGN:
      Mixed methods design comprising a within-subjects AB longitudinal survey, and a
      qualitative analysis of participant-generated data and researcher field notes
      from a World Cafe discussion group. SETTINGS: One university in Scotland.
      PARTICIPANTS: N = 66 undergraduate and postgraduate mental health nursing and
      counselling students. METHODS: Participants completed measures of cognitive and
      emotional attitudes towards, and knowledge about, people with borderline
      personality disorder before and after one of two film screenings. We conducted a
      World Cafe discussion group after the second screening. Resulting data were
      subject to a qualitative thematic analysis. RESULTS: Quantitative analysis
      revealed a five-factor cognitive and a single-factor emotional attitude
      structure. Cognitive-attitudinal items related to treatment deservingness and
      value of mixed treatment approaches improved across iterations. Total knowledge
      score did not change, but one item about borderline personality disorder as a
      precursor to schizophrenia received considerably more incorrect endorsement post
      screening. Qualitative analysis revealed five themes: Facilitation and inhibition
      of learning; promotion but not satiation of appetite for knowledge; challenging
      existing understanding; prompting creativity and anxiety; and initiating thinking
      about the bigger picture. CONCLUSIONS: Participants found the film thought
      provoking; it increased their appetite for knowledge. Findings suggest that
      screening should be delivered in conjunction with more didactic information about
      borderline personality disorder.

PMID- 29567594
TI  - Production of bioethanol and value added compounds from wheat straw through
      combined alkaline/alkaline-peroxide pretreatment.
AB  - An efficient scheme was developed for the conversion of wheat straw (WS) into
      bioethanol, silica and lignin. WS was pre-extracted with 0.2 mol/L sodium
      hydroxide at 30  degrees C for 5 h to remove about 91% of initial silica.
      Subsequently, the alkaline-pretreated solids were subjected to alkaline hydrogen
      peroxide (AHP) pretreatment with 40 mg hydrogen peroxide (H2O2)/g biomass at 50 
      degrees C for 7 h to prepare highly digestible substrate. The results of
      enzymatic hydrolysis demonstrated that the sequential alkaline-AHP pretreated WS
      was efficiently hydrolyzed at 10% (w/v) solids loading using an enzyme dosage of
      10 mg protein/g glucan. The total sugar conversion of 92.4% was achieved.
      Simultaneous saccharification and co-fermentation (SSCF) was applied to produce
      ethanol from the two-stage pretreated substrate using Saccharomyces cerevisiae
      SR8u strain. Ethanol with concentration of 31.1 g/L was produced. Through the
      proposed process, about 86.4% and 54.1% of the initial silica and lignin were
      recovered, respectively.

PMID- 29567595
TI  - The pH-based fed-batch for lipid production from Trichosporon oleaginosus with
      crude glycerol.
AB  - In this study, it was found that the optimal pH for the growth of Trichosporon
      oleaginosus was related to the fermentation medium. A neutral or weak acid pH
      condition was optimal for the growth of Trichosporon oleaginosus in the extract
      peptone-dextrose and wastewater sludge medium. Significant inhibition was
      observed at neutral pH in the wastewater sludge + crude glycerol medium due to
      the high soap content of the crude glycerol. By converting the soap to free fatty
      acid (FFA) at pH 5, the soap inhibition could be prevented. Fed-batch
      fermentation was employed to produce lipid from Trichosporon oleaginosus at pH 5
      controlled by feeding crude glycerol. A remarkably high biomass (65.63 g/L) and
      lipid (35.79 g/L) concentration were achieved from the pH-based fed-batch
      fermentation in this study.

PMID- 29567596
TI  - Techno-economic and profitability analysis of food waste biorefineries at
      European level.
AB  - Food waste represents a potential source to produce value-added materials
      replacing the use of virgin ones. However, the use of food waste as feedstock in
      biorefineries is still at an early stage of development and studies assessing its
      economic viability at large scale are lacking in the literature. This paper
      presents a techno-economic and profitability analysis of four food waste
      biorefineries that use wastes from tomato, potato, orange, and olive processing
      as feedstock. The study includes the assessment of potentially available
      quantities of those waste flows in Europe. Due to the low technology readiness
      level of this kind of biorefineries, a screening methodology to estimate the
      investment and manufacturing costs as well as two profitability ratios (the
      return on investment and the payback time) was adopted. Results show that not all
      the waste feedstocks have the same potential. The most profitable options are
      those related to implementing fewer plants, namely concentrating the production
      and capitalising on economies of scale while being at risk of increasing
      externalities, e.g. due to logistics of the feedstocks.

PMID- 29567597
TI  - A randomised field study evaluating the effectiveness of buccal meloxicam and
      topical local anaesthetic formulations administered singly or in combination at
      improving welfare of female Merino lambs undergoing surgical mulesing and hot
      knife tail docking.
AB  - This study was a field-based behavioural assessment of the pain responses to
      surgical mulesing modulated by a buccal formulation of meloxicam (Buccalgesic)
      and a topical local anaesthetic wound dressing (Tri-Solfen). 20 lambs were
      randomly allocated to each of: 1) Placebo and sham handled (Sham); 2) Placebo and
      mulesing (Mules); 3) Buccalgesic and mulesing (Mules+B); 4) Tri-Solfen and
      mulesing (Mules+T); 5) Placebo, Tri-Solfen and mulesing (Mules+T+P); 6)
      Buccalgesic, Tri-Solfen and mulesing (Mules+T+B). Lamb behaviour was observed by
      scan sampling every 15 min for 6 h post mulesing then for 1.5 h daily over the
      subsequent 10 days. Wound score, wound sensitivity and body weight were recorded
      on day 4, 7 and 10. On the day of mulesing, abnormal behaviours were reduced for
      all groups that received the analgesic drugs compared to the Mules group (P <
      0.05). Tri-Solfen reduced expression of abnormal behaviours in the first 4 h;
      Buccalgesic reduced expression of abnormal behaviours between 2 and 6 h; and
      combination treatment reduced expression of abnormal behaviours over the entire
      observation period. On the subsequent two days, the drug combination resulted in
      fewer abnormal postures than Tri-Solfen alone. The drug combination tended to
      result in lower pain sensitivity (965.3 g tolerated) than either Mules+T+P (828.8
      g), or Mules+B (791.2 g) on day 7 (P < 0.05). Use of Tri-Solfen and Buccalgesic
      singly or in combination improved the welfare of lambs undergoing surgical
      mulesing. The residual effect of pain and discomfort caused by mulesing, were
      evident despite provision of analgesic drugs.

PMID- 29567598
TI  - The influence of probiotic supplementation in broiler chickens on population and
      carcass contamination with Campylobacter spp. - Field study.
AB  - Campylobacter spp. is a food-borne pathogen occurring all over the world.
      According to European Food Safety Authority, in Europe, in 2015 the number of
      recorded and confirmed cases of Campylobacter spp. infections in humans has
      reached approximately 230,000. Poultry and poultry meat are considered to be the
      main sources of human infection, which triggers the discussion about the
      possibility of imposing obligatory control of Campylobacter spp. population at
      the level of primary poultry production. Recently, the use of probiotics in
      poultry is considered as a very promising alternative that could reduce infection
      rate in broiler chickens with Campylobacter spp. Although, there were some
      approaches made in vivo, up to date, there were no studies that would evaluate
      those issues under field conditions. A study was carried out in order to
      determine the feasibility of reducing infection rate in broiler chickens with
      Campylobacter spp. raised at a commercial farm, by the addition of multispecies
      probiotic (Lavipan, JHJ, Poland) that composed of Lactococcus lactis,
      Carnobacterium divergens, Lactobacillus casei, Lactobacillus plantarum and
      Saccharomyces cerevisae to the feed. Results of our study indicate that probiotic
      (Lavipan) added to a feed for broiler chickens was capable to reduce the extent
      of Campylobacter spp. invasion in the gastrointestinal tract of birds and,
      resultantly, to diminish contamination level in bird environment, which
      eventually contributed to the improved hygienic parameters of analyzed poultry
      carcasses. Additionally, this probiotic displayed promising immunomodulatory
      properties that may improve the effectiveness of the specific prophylaxis program
      applied in a flock of broiler chickens.

PMID- 29567599
TI  - Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic
      differentiation of mouse myoblast C2C12 cells.
AB  - Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of
      Vitamin C-conjugated tripeptides, which were originally developed as a component
      of a product for collagen synthesis enhancement or human dermal fibroblast
      growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic
      protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C
      AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline
      phosphatase, a typical marker of osteoblast differentiation. Vit C-AHK also
      stimulated the phosphorylation and translocation of Smad1/5/8 to the nucleus and
      phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and
      p38. In addition, Vit C-AHK enhanced the BMP-2-induced mRNA expression of
      osteoblast differentiation-related genes such as ALP, BMP-2, Osteocalcin, and
      Runx2. Our results suggest that Vit C-AHK exerts an enhancing effect on
      osteoblast proliferation and differentiation through activation of Smad1/5/8 and
      MAPK ERK1/2 and p38 signaling and without significant cytotoxicity. These results
      provide important data for the development of peptide-based bone-regenerative
      agents and treatment of bone-related disorders.

PMID- 29567600
TI  - Electron-deficient tripodal amide based receptor: An exclusive turn-on
      fluorescent and colorimetric chemo sensor for cyanide ion.
AB  - Here in, we have designed, synthesized and isolated sensor L, as an exclusive
      selective turn-on fluorescent chemo sensor for cyanide ion. The acetonitrile
      solution contains L with tetrabutyl ammonium cyanide, results sudden color change
      from colorless to yellowish-brown. Chemosensor L produced a strong fluorescence
      response with an enhancement of very high fluorescence intensity while addition
      of CN- ion and the strength of the chemosensor L towards cyanide binding is found
      to be 3.9813*104M-1. In order to use this sensor in practical application, we
      also prepared a cassette which is fabricated with sensor L and we succeeded to
      sense cyanide ion.

PMID- 29567601
TI  - Simultaneous determination of rosuvastatin and propranolol in their binary
      mixture by synchronous spectrofluorimetry.
AB  - Simultaneous determination of rosuvastatin calcium and propranolol hydrochloride
      using the first derivative synchronous spectrofluorimetry was described. This
      method involves measuring the synchronous fluorescence of both drugs in ethanol
      using, ? lambda = 60 nm then the first derivative was recorded and the peak
      amplitudes were measured at 350 and 374 nm for rosuvastatin calcium and
      propranolol hydrochloride, respectively. Under the optimum conditions, the linear
      ranges of rosuvastatin calcium and propranolol hydrochloride were 0.2-2 MUg/mL
      and 0.1-1 MUg/mL, respectively. The method was used for quantitative analysis of
      the drugs in raw materials and pharmaceutical dosage form. The validity of the
      proposed method was assessed according to an international conference on
      harmonization (ICH) guidelines.

PMID- 29567602
TI  - Cobalt and cobalt oxides N-codoped porous carbon derived from metal-organic
      framework as bifunctional catalyst for oxygen reduction and oxygen evolution
      reactions.
AB  - Metal-organic framework (MOF)-derived transition metal/metal oxide-carbon hybrids
      are promising cost-effective electrocatalysts to replace noble metal catalysts
      for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein,
      Co@CoO@Co3O4-N/C was prepared by two-step thermal treatment of Co-MOF
      ([Co(INA)2].0.5EtOH) (INA: isonicotinic acid). Firstly, Co-MOF, as precursor, was
      pyrolyzed at different temperatures in N2 atmosphere to obtain Co-N/C-T (T = 700,
      800, 900  degrees C) materials among which Co-N/C-800 shows remarkably high ORR
      activity. After oxidation treatment, Co-N/C-800 is transformed into Co@CoO@Co3O4
      N/C which exhibits enhanced electrocatalytic activities for both ORR and OER. The
      as-obtained Co@CoO@Co3O4-N/C has more positive onset potential (-0.136 V vs.
      Ag/AgCl) and higher limit current density (4.9 mA cm-2) than Co-N/C-800 (-0.143 V
      vs. Ag/AgCl and 3.9 mA cm-2), as well as better tolerance to methanol and
      stability (80.0%) than those of Pt/C (63.2%) for ORR. Co@CoO@Co3O4-N/C also
      displays outstanding OER performances, with lower overpotential (450 mV) than
      that of Co-N/C-800 (492 mV) at a current density of 10 mA cm-2. The excellent
      electrochemical performance of Co@CoO@Co3O4-N/C can be ascribed to uniformly
      dispersed Co-Nx active sites, strong synergistic effects between N-doped carbon
      support and Co@CoO@Co3O4 as well as ordered mesoporous structure, boosting mass
      transfer and accelerating electrocatalytic reaction.

PMID- 29567603
TI  - Performance of magnetic graphene oxide/diethylenetriaminepentaacetic acid
      nanocomposite for the tetracycline and ciprofloxacin adsorption in single and
      binary systems.
AB  - Adsorption of tetracycline (TC) and ciprofloxacin (CIP) in single and binary
      systems by diethylenetriaminepentaacetic acid-functionalized magnetic graphene
      oxide (DDMGO) was explored. DDMGO were characterized by scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron
      spectroscopy (XPS) and zeta potential measurements. The adsorption kinetics and
      equilibrium data of single antibiotic were well fitted by pseudo-second-order and
      Freundlich isotherm models, respectively. Negative DeltaGo values hinted the
      spontaneous nature of TC and CIP sorption. Moreover, the DeltaHo was positive for
      TC removal and negative for CIP removal, indicating that TC adsorption was
      endothermic and CIP adsorption was exothermic. Various experimental conditions
      (pH, ionic strength and foreign ions) presented an important influence on TC and
      CIP removal. In binary systems, TC sorption onto DDMGO exhibited stronger
      inhibition effect by the coexisting competitive antibiotics than that for CIP.
      The reusability experiment revealed that the DDMGO had an excellent regeneration
      performance in single and binary systems. TC and CIP removal mechanism on DDMGO
      was mainly dependent on pi-pi interaction, hydrogen bonds and amidation reaction.
      Besides, TC and CIP uptake could also be explained by cation-pi and electrostatic
      interaction, respectively. These findings showed that DDMGO was an efficient and
      reusable adsorbent for antibiotics elimination.

PMID- 29567604
TI  - Design of reduced graphene oxide decorated with DOPO-phosphanomidate for enhanced
      fire safety of epoxy resin.
AB  - A facile approach was developed to simultaneously functionalize and reduce
      graphene oxide (GO) with 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide
      (DOPO)-phosphonamidate. To achieve stable dispersion and effective stress
      transfer, graphene was functionalized by polyethyleneimine (PEI). To improve the
      fire resistance of bare graphene, DOPO was grafted on the surface of PEI-reduced
      graphene oxide (PEI-rGO) to obtain the grafting of DOPO-phosphonamidate on the
      graphene. A morphological study indicated that, due to the good interfacial
      interaction between the functionalized graphene and epoxy (EP), functionalized
      reduced graphene oxide (f-rGO) was well-dispersed in the host polymer.
      Incorporation of 3.0 wt% f-rGO led to the increased char yields of the EP.
      Moreover, the storage modulus and glass transition temperature were improved,
      respectively. The evaluation of combustion behavior demonstrated that the peak
      heat release rate and total heat release of f-rGO/EP were reduced by 31% and
      34.3%, respectively, compared to those of neat EP. This dramatically reduced fire
      hazards were mainly attributed to the synergistic effect of f-RGO. On one hand,
      DOPO-phosphonamidate on the surface of GO promoted flame inhibition in the gas
      phase while protecting the rGO against fire. On the other hand, the adsorption
      and barrier effect of rGO inhibited the heat and gas release, respectively,
      promoting the formation of graphitized carbons.

PMID- 29567605
TI  - Sodium dodecyl sulfate intercalated and acrylamide anchored layered double
      hydroxides: A multifunctional adsorbent for highly efficient removal of Congo
      red.
AB  - In this study, a novel adsorbent was designed and synthesized via intercalation
      of sodium dodecyl sulfate (SDS) in the interlayer, and subsequent grafting of
      acrylamide (AM) on the layer of layered double hydroxides (LDH) (named as AM/SDS
      LDH), and applied for congo red (CR) removal. The morphological structure,
      wettability and physicochemical properties of the adsorbents were thoroughly
      characterized using SEM, EDS, N2-adsorption/desorption isotherm, static contact
      angle, XRD and FTIR. Results elucidated that SDS and AM were successfully
      introduced into the interlayer and onto the layer of LDH, respectively.
      Adsorption experimental results suggested that the maximum adsorption capacities
      of CR on SDS-LDH and AM/SDS-LDH at pH 5.0 and 293 K were 714.29 and 1118.78 mg/g,
      respectively, which were much higher than that of CR on LDH (588.24 mg/g). Based
      on the BET, XRD and FTIR analysis, the higher adsorption capacity of AM/SDS-LDH
      was mainly attributed to high surface area, large basal spacing as well as the
      abundant NH2 groups. The experimental data can be well fitted by pseudo-second
      order kinetic and Langmuir isotherm models. Thermodynamic parameters indicated
      the adsorption process was favorable under the higher temperature condition. The
      synergistic effect existed during the adsorption process of CR onto AM/SDS-LDH,
      including the electrostatic interactions, anion exchange and hydrophobic
      hydrophobic interactions. Overall, this study provided a strategy for design and
      fabrication of highly efficient adsorbents.

PMID- 29567606
TI  - Formation of block-copolymer-templated mesoporous silica.
AB  - In situ attenuated total reflectance Fourier transform infrared spectroscopy is
      used to monitor the chemical evolution of the mesoporous silica SBA-15 from
      hydrolysis of the silica precursor to final silica condensation after the
      particle formation. Two silica precursors, tetraethyl orthosilicate (TEOS) or
      sodium metasilicate (SMS) were used, and the effects of additive (heptane and
      NH4F) concentrations were studied. Five formation stages are identified when TEOS
      is used as the precursor. The fourth stage correlates with the appearance and
      evolution of diffraction peaks recorded using in situ small angle X-ray
      diffraction. Details of the formed silica matrix are observed, e.g. the ratio
      between six-fold cyclic silica rings and linear bonding increases with the NH4F
      concentration. The TEOS hydrolysis time is independent of the NH4F concentration
      for small amounts of heptane, but is affected by the size of the emulsion
      droplets when the heptane amount increases. Polymerization and condensation rates
      of both silica precursors are affected by the salt concentration. Materials
      synthesized using SMS form significantly faster compared to TEOS-materials due to
      the pre-hydrolysis of the precursor. The study provides detailed insights into
      how the composition of the synthesis solution affects the chemical evolution and
      micellar aggregation during formation of mesoporous silica.

PMID- 29567607
TI  - Facile construction of terpridine-based metallo-polymers in hydrogels, crystals
      and solutions directed by metal ions.
AB  - Driven by tunable metal-ligand interactions, a polydentate ligand TC containing
      terpyridine and carboxylic acid units was developed to construct metallo-polymers
      that showed multiple aggregation modes with controlled macroscopic properties. In
      the presence of different kind of Zn2+ ions or NaOH, TC could form metallo
      polymers via pi-pi stacking and metal-ligand interaction that further trapped
      water molecules, resulting in hydrogels and crystals. Moreover, these TC/Zn2+
      hydrogels could transform to soluble and fluorescent aggregates in the presence
      of NaOH due to the formation of binuclear metallo-polymers with enhanced ICT
      emission. The metal-ligand interactions tuned by different metal salts in gels,
      crystals, and sols were also studied and illustrated in detail, it was also
      proved that water was an essential linker for constructing Na+-based metallo
      polymers from the TC/NaOH crystal data. This work demonstrated the engineered
      coordination pathways in generating controllable hydrogels and metallo-polymers
      for the first time, which led to novel approach for facilely constructing a
      number of hydrogels with tailorable macroscopic properties.

PMID- 29567608
TI  - Evaluating tetracycline degradation pathway and intermediate toxicity during the
      electrochemical oxidation over a Ti/Ti4O7 anode.
AB  - Tetracycline (TC) is one of the most widely used antibiotics with significant
      impacts on human health and thus it needs appropriate approaches for its removal.
      In the present study, we evaluated the performance and complete pathway of the TC
      electrochemical oxidation on a Ti/Ti4O7 anode prepared by plasma spraying.
      Morphological data and composition analysis indicated a compact coating layer on
      the anode, which had the characteristic peaks of Ti4O7 as active constituent. The
      TC electrochemical oxidation on the Ti/Ti4O7 anode followed a pseudo-first-order
      kinetics, and the TC removal efficiency reached 95.8% in 40 min. The influential
      factors on TC decay kinetics included current density, anode-cathode distance and
      initial TC concentration. This anode also had high durability and the TC removal
      efficiency was maintained over 95% after five times reuse. For the first time, we
      unraveled the complete pathway of the TC electrochemical oxidation using high
      performance liquid chromatograph (HPLC) and gas chromatograph (GC) coupled with
      mass spectrometer (MS). .OH radicals produced from electrochemical oxidation
      attack the double bond, phenolic group and amine group of TC, forming a primary
      intermediate (m/z = 461), secondary intermediates (m/z = 432, 477 and 509) and
      tertiary intermediates (m/z = 480, 448 and 525). The latter were further oxidized
      to the key downstream intermediate (m/z = 496), followed by further downstream
      intermediates (m/z = 451, 412, 396, 367, 351, 298 and 253) and eventually short
      chain carboxylic acids. We also evaluated the toxicity change during the
      electrochemical oxidation process with bioluminescent bacteria. The
      bioluminescence inhibition ratio peaked at 10 min (55.41%), likely owing to the
      high toxicity of intermediates with m/z = 461, 432 and 477 as obtained from
      quantitative structure activity relationship (QSAR) analysis. The bioluminescence
      inhibition ratio eventually decreased to 16.78% in 40 min due to further
      transformation of TC and intermediates. By comprehensively analyzing the
      influential factors and complete degradation pathway of TC electrochemical
      oxidation on the Ti/Ti4O7 anode, our research provides deeper insights into the
      risk assessment of intermediates and their toxicity, assigning new perspectives
      for practical electrochemical oxidation to effectively eliminate the amount and
      toxicity of TC and other antibiotics in wastewater.

PMID- 29567609
TI  - Effect of gestational exposure to arsenic on puberty in offspring female mice.
AB  - We examined the vaginal opening day, ovary and uterus organ coefficient,
      reproductive hormone levels of luteinizing hormone (LH) and follicle stimulating
      hormone (FSH), mRNA and protein expression levels of kiss-1, hypothalamus
      gonadotrophin releasing hormone 1 (GnRH1), organic cation transporters 2 (Oct2)
      and transcription termination factor 1 (Ttf1) in different pubertal ages [late
      lactation (18 days), pre-puberty (21-22 days), puberty (23-27 days; with respect
      to vaginal opening) and maturity (65 days)] of offspring females, to evaluate the
      effect of arsenic (As) on puberty initiation after maternal exposure to As at
      different concentration [0, 0.15, 1.5 and 15 mg/L As(III)] during gestational
      period. The results showed that the vaginal opening time was significantly
      advanced in utero in mice exposed to As compared to the control. The hormone
      level of LH was significantly increased in the mice treated with 15 mg/L of
      As(III) at puberty compared to the control. During puberty, the mRNA expression
      levels of kiss-1, GnRH1, Oct2 and Ttf1 in the hypothalamus were significantly
      increased in the group treated with 15 mg/L of As(III) compared to the control.
      The protein expressions of Kisspeptin, GnRH1, Oct2 and Ttf1 in the hypothalamus
      were significantly increased in the pubertal females, while Oct2 and Ttf1
      expression levels were significantly decreased in the matured females compared to
      the control, which is in line with the transcriptional changes of related mRNA
      expressions. In brief, this study demonstrated that maternal exposure to As
      during gestational period could result in early onset of puberty in offspring
      females.

PMID- 29567610
TI  - Removal of rhodamine 6G with different types of clay minerals.
AB  - With an increased use of color dye in textile industries and elevated fabrics
      output, more scientific studies and technology developments are needed to
      effectively treat wastewater containing dyes. However, better understanding of
      the interactions between dyes and suspended solids is a necessity to advance such
      developments. In this study the interactions between rhodamine 6G (R6G), a
      cationic dye, and different types of clays minerals, commonly found in the
      wastewater sludge, were elucidated. The uptake of R6G on the clay minerals was
      attributed to cation exchange on the external surfaces of non-swelling clays, and
      at both external and interlayer spaces for swelling clays. In the interlayer of
      montmorillonite, the R6G molecules form monolayer and bilayer configurations
      under low and high uptake levels. The significant amounts of R6G uptake indicate
      that clay minerals are good sorbents for the removal of cationic dyes from water.
      And the R6G could be readily removed in wastewater treatment by adding small
      amount of clays and flocculated the clays out.

PMID- 29567611
TI  - Ecological risks posed by ammonia nitrogen (AN) and un-ionized ammonia (NH3) in
      seven major river systems of China.
AB  - Previous studies showed that continuous exposure to ammonia nitrogen (AN)
      contributed to regional losses of benthic invertebrate diversity in China. Yet,
      the overall ecological risk of AN to aquatic organisms in major riverine systems
      of China has not been appropriately studied. Our research then investigated
      temporal (seasonally/yearly) and spatial distributions of AN and un-ionized
      ammonia (NH3) in major Chinese river basins using historic data generated between
      2007 and 2014, and developed risk assessment criteria. Our results showed that
      the highest average AN concentrations occurred during winter (0.82-2.76 mg/L) and
      the lowest during summer (0.36-0.78 mg/L). NH3 exhibited the opposite trend with
      the highest average concentrations mostly observed during spring (15.13-92.84
      MUg/L) and the lowest concentrations mainly during winter (10.53-45.43 MUg/L).
      Both AN and NH3 concentrations steadily increased and reached maximum levels in
      2008 (AN: 1.22 mg/L and NH3: 50.65 MUg/L), and then decreased. Temporal trends
      showed that the Yellow, Hai, and Huai river basins had the highest AN and NH3
      concentrations. Subsequently, conventional (hazard quotients) and probabilistic
      (joint probability curves) methods were applied to assess the hazards and risks
      posed by AN and NH3. The results showed that the probability of exceeding the
      acute toxicity threshold for 5% of species (exposed to AN or NH3) was less than
      13.3% and gradually decreased over time. To protect aquatic organisms, an acute
      criterion of 51.4 MUg NH3/L and a chronic criterion of 1.14 mg AN/L at pH = 7.5,
      20  degrees C were developed and are recommended for future risk assessment
      studies.

PMID- 29567612
TI  - Is the aquatic toxicity of cationic polyelectrolytes predictable from selected
      physical properties?
AB  - Cationic acrylamide-based polyelectrolytes (cPAM) are widely used in industry.
      They can be designed for optimal performance in a specific application, but this
      opportunity means the environmental safety of all different alternatives needs to
      be addressed. Both the inclusion of environmental toxicity as a design variable
      and the establishment of relationships between structure and ecotoxicity are thus
      current challenges. The aim of this study was to assess whether structural
      variables such as molecular weight, charge density and the integrative intrinsic
      viscosity parameter can be used to predict the environmental safety of cPAMs, as
      well as if these relationships are stable when the biological models change. Five
      cPAMs comprising molecular weight and charge density gradients were tested
      against bacteria, microalgae, macrophytes and daphnids. While correlations were
      found between physical properties of cPAMs as expected, no clear ecotoxicity
      patterns could be identified. All cPAMs can be classified as harmful to aquatic
      life on the basis of the responses elicited in the most sensitive organisms,
      microalgae and daphnids. Unicellular bacteria were the least sensitive eco
      receptors possibly due to cell wall structure or the protective effect of the
      ionic strength of the test medium. The macrophytes were also tolerant to cPAMs
      exposure, which may be related to exposure avoidance mechanisms. The order of
      toxicity of cPAMs depended on the test organism, preventing the establishment of
      stable structure-ecotoxicity relationships. Therefore, the study leads to the
      overall generalist recommendation of relying on the most sensitively responding
      test organisms when developing new (eco)safe-by-design cPAMs.

PMID- 29567613
TI  - Ecological and health risk assessment of potentially toxic elements in the major
      rivers of Pakistan: General population vs. Fishermen.
AB  - Large amounts of potentially toxic elements (PTEs) have, and continue to be,
      released into the freshwater ecosystems of Pakistan. However, there is limited
      information available on the ecological risk of PTEs from sediments and fish
      consumption, for both the general population and fishermen, at the national scale
      in Pakistan. In this study, water, sediments and fish samples were collected from
      major rivers (Chenab, Upper Indus, Lower Indus and Kabul) across Pakistan and
      analyzed through Inductively Coupled Plasma Mass Spectrometer (ICP-MS),
      Inductively Coupled Plasma Atomic Emission Spectroscopy ICP-AES and Atomic
      Fluorescence Spectrometry (AFS), respectively. Ecological risk analysis of
      sediments revealed that Cd posed a high ecological risk in the Upper Indus and
      Chenab, a considerable risk in the Lower Indus, and moderate risk in the Kabul.
      The target hazard quotient of As through fish tissue consumption exceeded safety
      levels for fishermen at all the rivers, where Cd exceeded at Upper Indus and
      Chenab, and Pb for Chenab fishermen only. For the general population, PTE
      ingestion through fish tissues was within the safety limits at all rivers.
      Meanwhile, the total target hazard quotient in all three rivers exceeded the
      safety limit, representing a high risk for the fishermen of Pakistan. The results
      show that ecological risk and target hazard quotient assessment not only provides
      valuable information for future research in terms of PTE contamination in the
      major rivers of Pakistan, but also all the metal pollutants from rivers finally
      reach to Arabian Sea, therefore might pose a risk to marine ecosystem at national
      and international scale.

PMID- 29567614
TI  - Risk of a false decision on conformity of an environmental compartment due to
      measurement uncertainty of concentrations of two or more pollutants.
AB  - Risks of false decisions in conformity assessment of an environmental compartment
      due to measurement uncertainty of concentrations of two or more pollutants are
      discussed. Even if the assessment of conformity for each pollutant in the
      compartment is successful, the total probability of a false decision concerning
      the compartment as a whole might still be significant. A model of the total
      probability of a false decision, formulated on the base of the law of total
      probability, is used, for example, for a study of test results of total suspended
      particulate matter (TSPM) concentration in ambient air near to three independent
      stone quarries located in Israel, as the sources of the air pollution. Total
      probabilities of underestimation of TSPM concentration (total risk of the
      inhabitants) and overestimation (total risk of the stone producers) are evaluated
      as a combination of the particular risks of air conformity assessment concerning
      TSPM concentration for each quarry. These probabilities characterize conformity
      of the TSPM concentration in the region of the quarries as a whole. Core code
      developed in R programming environment for the calculations is provided.

PMID- 29567615
TI  - Enumeration of the constitutional isomers of environmentally relevant substituted
      polycyclic aromatic compounds.
AB  - Polycyclic aromatic compounds (PACs) are a diverse group of environmentally
      relevant compounds which can be persistent, bioaccumulative and toxic. The cyclic
      backbone of PACs can be substituted with halogens or hydrocarbon chains. The
      amount and positions of these substituents influence their toxicity. For many
      classes of PACs, substitution creates mixtures containing large numbers of
      isomers. For example, 209 theoretical isomers of chlorinated biphenyls are
      possible. Many other classes of environmentally relevant PACs exist where the
      number of theoretical isomers are unknown. Here, a mathematical approach using
      molecular symmetry and the binomial coefficient is presented that determines the
      number of theoretical isomers of PACs. The approach was validated on PACs with
      known isomer numbers and then applied to PACs with unknown isomer numbers. When
      the approach was applied to alkylated polycyclic aromatic hydrocarbons, the
      possible theoretical isomers ranged from 2 for C1 naphthalene up to 19 502 for C6
      dibenzo(ah)anthracene. Heterocyclic PACs had similar numbers ranging from 4
      isomers for C1 dibenzothiophene to 13 938 for C6 dibenzo[a,i]carbazole. The work
      presented will aide analytical chemists and ecotoxicologists in their efforts to
      develop methods to measure these compounds, and in attempting to assess the
      toxicity and environmental fate of individual isomers.

PMID- 29567617
TI  - Health related quality of life and its associated factors among community
      dwelling older people in Sri Lanka: A cross-sectional study.
AB  - BACKGROUND: Population ageing has become a public health issue as it is
      associated with increased morbidity, institutionalization and death. These may
      directly affect health-related quality of life (HRQOL) of older people. PURPOSE:
      The aim of the study was to investigate HRQOL and its associated factors among
      community-dwelling older people in Kandy district, Sri Lanka. METHOD: This cross
      sectional survey involved 1300 older people. The Euro 5D-3L, International
      Physical Activity Questionnaire, body mass index, handgrip strength were used to
      measure HRQOL, physical activity and nutritional status of older people
      respectively. Factors associated with health-related quality of life were
      identified through complex sample logistic regression analysis. RESULTS: Majority
      of older people (81.9%) reported poor health-related quality of life. Middle old
      (aOR: 12.06, 95% CI: 5.76, 25.23), very old (aOR: 174.74, 95% CI: 39.74, 768.38),
      vegetarian diets (aOR: 2.13, 95% CI: 1.14, 3.96), under-nutrition (aOR: 3.41, 95%
      CI: 1.65, 7.04) and over-nutrition (aOR: 1.85, 95% CI: 1.04, 3.28) were
      significantly associated with poor HRQOL. Using dentures (aOR: 0.05, 95% CI:
      0.28, 0.90) was found as a protective factor for poor HRQOL. CONCLUSIONS: HRQOL
      was poor among community-dwelling older people in Kandy district. Nutrition
      related factors need to be further investigated to improve HRQOL among older
      people.

PMID- 29567616
TI  - Age-dependent regulation of antioxidant genes by p38alpha MAPK in the liver.
AB  - p38alpha is a redox sensitive MAPK activated by pro-inflammatory cytokines and
      environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work
      was to assess whether p38alpha controls the antioxidant defense in the liver, and
      if so, to elucidate the mechanism(s) involved and the age-related changes. For
      this purpose, we used liver-specific p38alpha-deficient mice at two different
      ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young
      p38alpha knock-out mice exhibited a decrease in GSH levels and an increase in
      GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in
      p38alpha had higher hepatic GSH levels and lower GSSG/GSH ratio than young
      p38alpha knock-out mice. Liver-specific p38alpha deficiency triggered a dramatic
      down-regulation of the mRNAs of the key antioxidant enzymes glutamate cysteine
      ligase, superoxide dismutase 1, superoxide dismutase 2, and catalase in young
      mice, which seems mediated by the lack of p65 recruitment to their promoters. Nrf
      2 nuclear levels did not change significantly in the liver of young mice upon
      p38alpha deficiency, but nuclear levels of phospho-p65 and PGC-1alpha decreased
      in these mice. p38alpha-dependent activation of NF-kappaB seems to occur through
      classical IkappaB Kinase and via ribosomal S6 kinase1 and AKT in young mice.
      However, unexpectedly the long-term deficiency in p38alpha triggers a
      compensatory up-regulation of antioxidant enzymes via NF-kappaB activation and
      recruitment of p65 to their promoters. In conclusion, p38alpha MAPK maintains the
      expression of antioxidant genes in liver of young animals via NF-kappaBeta under
      basal conditions, whereas its long-term deficiency triggers compensatory up
      regulation of antioxidant enzymes through NF-kappaBeta.

PMID- 29567618
TI  - Subjective and objective sleep quality in elderly individuals: The role of
      psychogeriatric evaluation.
AB  - Aging affects sleep and sleep problems are common in older individuals. However,
      the relationship between objective and subjective tools for analysing sleep and
      psycho-geriatric variables have not been tested in institutionalised older
      individuals. This work analyses sleep quality by using actigraphy as an objective
      tool and validates the Athens and Oviedo sleep questionnaires in octogenarian
      elderly individuals as subjective scales of sleep perception. All patients wore
      an actigraph device for one week and then completed the Athens and Oviedo
      clinical sleep-evaluation questionnaires. Morning cortisol levels in blood plasma
      and saliva samples were also measured to assess the association between objective
      and reported sleep patterns. Age, gender, and psycho-geriatric evaluations,
      including Barthel, Tinetti, and Mini-Mental scale measurements were analysed as
      variables with the potential to confound the strength of any such associations.
      There was a significant inverse correlation between the number of awakenings and
      the time spent awake during night assessed by actigraphy and the total Oviedo
      questionnaire score, but no significant associations for the other parameters.
      The blood cortisol concentration appears to be a marker of insomnia related to
      sleep times of less than four hours and diagnosis of insomnia based on Athens
      scale and thus, represents a potential marker for sleep interventions.

PMID- 29567619
TI  - Tweeting weight loss: A comparison of #thinspiration and #fitspiration
      communities on Twitter.
AB  - Thinspiration and fitspiration represent contemporary online trends designed to
      inspire viewers towards the thin ideal or towards health and fitness
      respectively. The aim of the present study was to compare thinspiration and
      fitspiration communities on Twitter. A total of 3289 English-language tweets with
      hashtags related to thinspiration (n = 1181) and fitspiration (n = 2578) were
      collected over a two-week period. Network analysis showed minimal overlap between
      the communities on Twitter, with the thinspiration community more closely
      connected and having greater information flow than the fitspiration community.
      Frequency counts and sentiment analysis showed that although the tweets from both
      types of accounts focused on appearance and weight loss, fitspiration tweets were
      significantly more positive in sentiment. It was concluded that the thinspiration
      tweeters, unlike the fitspiration tweeters, represent a genuine on-line community
      on Twitter. Such a community of support may have negative consequences for
      collective body image and disordered eating identity.

PMID- 29567620
TI  - Social stress response in adolescents with bipolar disorder.
AB  - OBJECTIVE: Theoretical models posit that stressors contribute to the onset and
      maintenance of bipolar disorder in adolescence through disruptions in stress
      physiology, but physiological response to stressors has not been evaluated in
      adolescents with bipolar illness. The present study tests the hypothesis that
      adolescents with bipolar disorder will have greater reactivity to a laboratory
      social stress task than healthy adolescents. METHOD: Adolescents with bipolar
      illness (n = 27) and healthy adolescents (n = 28) completed a modified version of
      the Trier Social Stress Task. Stress response was assessed using high frequency
      heart rate variability (HF-HRV), heart rate (HR), mean arterial blood pressure
      (MAP), salivary cortisol, and subjective stress. Multilevel models were used to
      test for group differences in resting-state physiology, and stress reactivity and
      recovery. RESULTS: Adolescents with bipolar disorder had greater reactivity in HF
      HRV (z = 3.32), but blunted reactivity in MAP (z = -3.08) and cortisol (z = 
      2.60), during the stressor compared to healthy adolescents. They also had lower
      resting HF-HRV (z = -3.49) and cortisol (z = -2.86), and higher resting HR (z =
      3.56), than healthy adolescents. CONCLUSIONS: These results indicate that bipolar
      disorder is associated with disruptions in autonomic and endocrine response to
      stress during adolescence, including greater HF-HRV reactivity. Further research
      should evaluate whether these individual differences in stress physiology precede
      and predict the onset of mood episodes.

PMID- 29567622
TI  - Th9 lymphocytes and functions of interleukin 9 with the focus on IBD pathology.
AB  - The work presents the newest knowledge on a new phenotype of T helper lymphocytes
      (Th9) and on Interleukin 9 (IL-9). Processes leading to transformation of naive T
      lymphocyte into Th9 lymphocytes are presented, including the role of IL-4 and
      TGFbeta signaling. Involvement of transcription factor network in production of
      IL-9 is described. Other cells capable of expressing IL-9 and secreting IL-9 are
      portrayed. Diversity of IL-9 effects caused by activation of IL-9 receptors on
      various types of cells is presented. Principal effects of the activation of IL-9
      receptor on T-cells seem to be antiapoptotic and stimulatory which leads to
      enhanced defense against parasitic infection and cancer development but, from the
      other side, it perpetuate chronic inflammation in autoimmune diseases and
      allergic processes. In the last years the role of IL-9 in autoimmune diseases
      such as rheumatic diseases and inflammatory bowel disease gained importance since
      the increased expression of this cytokine has been observed in animal models of
      intestinal inflammation and in groups of patients with ulcerative colitis. It was
      also noted that neutralization of IL-9 in animal models of ulcerative colitis
      leads to amelioration of inflammatory process, what could have significance in
      the treatment of this disease in humans in the future.

PMID- 29567623
TI  - Post-polyploid diploidization and diversification through dysploid changes.
AB  - Whole-genome duplications are widespread across land plant phylogenies and
      particularly frequent in ferns and angiosperms. Genome duplications spurred the
      evolution of key innovations associated with diversification in many angiosperm
      clades and lineages. Such diversifications are not initiated by genome doubling
      per se. Rather, differentiation of the primary polyploid populations through a
      range of processes results in post-polyploid genome diploidization. Structural
      diploidization gradually reverts the polyploid genome to one functionally diploid
      like through chromosomal rearrangements which frequently result in dysploid
      changes. Dysploidies may lead to reproductive isolation among post-polyploid
      offspring and significantly contribute to speciation and cladogenetic events.

PMID- 29567621
TI  - Diet matters: Glucocorticoid-related neuroadaptations associated with calorie
      intake in female rhesus monkeys.
AB  - Exposure to psychosocial stressors increases consumption of palatable,
      calorically dense diets (CDD) and the risk for obesity, especially in females.
      While consumption of an obesogenic diet and chronic stress have both been shown
      to decrease dopamine 2 receptor (D2R) binding and alter functional connectivity
      (FC) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc), it
      remains uncertain how social experience and dietary environment interact to
      affect reward pathways critical for the regulation of motivated behavior. Using
      positron emission tomography (PET) and resting state functional connectivity
      magnetic resonance neuroimaging (rs-fMRI), in female rhesus monkeys maintained in
      a low calorie chow (n = 18) or a dietary choice condition (chow and a CDD; n =
      16) for 12 months, the current study tested the overarching hypothesis that the
      adverse social experience resulting from subordinate social status would interact
      with consumption of an obesogenic diet to increase caloric intake that would be
      predicted by greater cortisol, lower prefrontal D2R binding potential (D2R-BP)
      and lower PFC-NAcc FC. Results showed that the consequences of adverse social
      experience imposed by chronic social subordination vary significantly depending
      on the dietary environment and are associated with alterations in prefrontal D2R
      BP and FC in NAcc-PFC sub-regions that predict differences in caloric intake,
      body weight gain, and fat accumulation. Higher levels of cortisol in the chow
      only condition were associated with mild inappetence, as well as increased
      orbitofrontal (OFC) D2R-BP and greater FC between the NAcc and the dorsolateral
      PFC (dlPFC) and ventromedial PFC (vmPFC). However, increased cortisol release in
      females in the dietary choice condition was associated with reduced prefrontal
      D2R-BP, and opposite FC between the NAcc and the vmPFC and dlPFC observed in the
      chow-only females. Importantly, the degree of these glucocorticoid-related
      neuroadaptations predicted significantly more total calorie intake as well as
      more consumption of the CDD for females having a dietary choice, but had no
      relation to calorie intake in the chow-only condition. Overall, the current
      findings suggest that dietary environment modifies the consequences of adverse
      social experience on reward pathways and appetite regulation and, in an
      obesogenic dietary environment, may reflect impaired cognitive control of food
      intake.

PMID- 29567624
TI  - Functional inactivation of the orbitofrontal cortex disrupts context-induced
      reinstatement of alcohol seeking in rats.
AB  - BACKGROUND: The high rate of relapse to drug use remains a central challenge to
      treating drug addiction. In human and rat models of addiction, environmental
      stimuli in contexts associated with previous drug use can provoke a relapse of
      drug seeking. Pre-clinical studies have used the ABA renewal procedure to study
      context-induced reinstatement of drug seeking. In the current study, we studied
      the role of the orbitofrontal cortex (OFC) in context-induced reinstatement to
      alcohol. METHODS: We trained male and female rats to self-administer alcohol in
      context A, extinguished drug-reinforced responding in a distinct context B, and
      assessed context-induced reinstatement in context A or B (control group). Next,
      we determined the effect of context-induced renewal of alcohol-seeking behavior
      on the expression of Fos (a neuronal activity marker) in the OFC. Finally, we
      determined the effect of reversible inactivation by GABAa and GABAb receptor
      agonists (i.e., muscimol and baclofen, respectively) in the OFC. RESULTS AND
      CONCLUSIONS: There were no differences between male and female rats in context
      induced reinstatement of alcohol-seeking behavior. Re-exposure to Context A, but
      not Context B, reinstated alcohol-seeking behavior and increased expression of
      the neural activity marker Fos in the OFC. Reversible inactivation of the OFC
      with muscimol and baclofen attenuated context-induced reinstatement. Our data
      indicated that the OFC mediates context-induced reinstatement of alcohol-seeking
      behavior.

PMID- 29567625
TI  - The dual-process model in young adults with a consistent binge drinking
      trajectory into adulthood.
AB  - BACKGROUND: Binge Drinking (BD) generally declines once students have left
      university. However, many individuals continue to partake in BD into adulthood,
      constituting a scarcely investigated high-risk group towards whom interventions
      should be prioritized. Following the dual-process model, we examined the
      relationship between BD and both the reflective system (executive functions) and
      the affective system (alcohol bias) in young adults with a consistent BD
      trajectory. We considered impulsivity as a moderator in the relationship between
      BD and alcohol bias. METHODS: A cohort of 63 (31?) young adults were followed for
      eleven years (18-29 years old). In the last assessment, participants, with high
      and low drinking trajectories underwent neuropsychological assessment of
      executive functions (working memory [SOPT], cognitive flexibility [TMT -Verbal
      Fluency], inhibition [Stroop]) and alcohol bias (Addiction Stroop). The Barratt
      Impulsivity Scale measured impulsivity. Generalized linear mixed models and
      regression-based moderation models were applied. RESULTS: BD was associated with
      weak inhibitory control, poor working memory and greater alcohol bias moderated
      by non-planning impulsivity. At moderate levels of non-planning impulsivity, BD
      was associated with greater alcohol bias. This association was not found at high
      levels of impulsivity. These deficits were related to loss of control over
      drinking and severity of alcohol use. CONCLUSIONS: The imbalance between poor
      cognitive control and greater alcohol bias may contribute to the persistence of
      BD into adulthood. The findings highlight the complexities of the dual-process
      model, with intervention implications.

PMID- 29567627
TI  - Recurrent pseudotumoral relapses in multiple sclerosis: a case report.
AB  - OBJECTIVES: Multiple sclerosis (MS) is the most common chronic disabling disease
      of the central nervous system (CNS) in young adults. It is characterized by the
      presence of multiple demyelinating inflammatory lesions disseminated in the CNS.
      Pseudotumoral lesions (PL) are rarely observed in patients with MS. METHODS:
      These atypical lesions can pose a diagnostic problem, especially when they are
      present at disease onset. RESULTS: Most MS patients with PLs only have a single
      episode throughout their disease course, which reflects its low tendency of
      recurrence. CONCLUSIONS: We report the rare case of a 34-year-old MS patient who
      suffered from recurrent pseudotumoral episodes during follow-up.

PMID- 29567626
TI  - Trends in and correlates of medical marijuana use among adults in the United
      States.
AB  - BACKGROUND: Trends in and correlates of medical marijuana use are important to
      inform ongoing clinical, research, policy, and programmatic efforts. This study
      assessed trends in and correlates of medical marijuana use among U.S. adults.
      METHODS: We analyzed data from approximately 147,200 U.S. civilians aged 18 or
      older who participated in the 2013-2015 National Surveys on Drug Use and Health.
      Descriptive analyses, multivariable logistic regressions, and zero-truncated
      native binomial regressions were applied. RESULTS: Among U.S. adults, the
      prevalence of medical marijuana use increased from 1.2% in 2013 to 1.6% in 2015
      (p = 0.0007). After adjusting for covariates, adults residing in medical
      marijuana states (states with legalized medical marijuana use) were 1.3 times
      more likely to use marijuana medically in 2015 than in 2013 (adjusted odds ratio
      (AOR) = 1.3, 95% confidence interval (CI) = 1.03-1.61), and adults in nonmedical
      marijuana states were 1.4 times more likely to report medical marijuana use in
      2015 than in 2013 (AOR = 1.4, 95% CI = 1.05-1.90). Among adults who used
      marijuana exclusively for medical purposes in the past 12 months, trends in 12
      month cannabis use disorders, daily or near daily use, and the number of days of
      marijuana use remained unchanged during 2013-2015. We identified how correlates
      of medical marijuana use among adults in medical marijuana states differed from
      their counterparts in nonmedical marijuana states. CONCLUSIONS: Adults were more
      likely to use marijuana medically in 2015 than in 2013 in both medical and
      nonmedical marijuana states. Clinicians need to learn about and address evolving
      patterns of medical marijuana use in patients.

PMID- 29567628
TI  - Coronary computed tomography angiography and endocardial leads - Image quality in
      320-row CT using iterative reconstruction.
AB  - PURPOSE: To investigate whether the presence of endocardial leads has an impact
      on image quality in coronary computed tomography angiography (CCTA), when current
      technique is employed using a 320-row computed tomography and iterative
      reconstruction. MATERIALS AND METHODS: CCTA was performed in 1641 patients, from
      these we identified 51 patients (study group) with endocardial leads and 51
      matched partners (control group) without endocardial leads. Noise was determined
      in the ascending aorta and the left ventricle; signal-to-noise ratio (SNR) and
      contrast-to-noise ratio (CNR) were determined in the left and right coronary
      artery. Subjective image quality was rated separately for the 15 segments of the
      coronary arteries by 2 radiologists. RESULTS: Current CCTA technique still shows
      slight impairment of objective image quality in patients with endocardial leads
      with inferior SNR in the aorta (median 15.04 versus 16.6; p = 0.004) and inferior
      SNR in the left/right coronary artery (median 15.3/13.81 versus 16.1/15.41; p =
      0.013/0.002). CNR of the left/right coronary artery was also inferior (median
      17.4/16.46 versus 19.26/19.24; p = 0.002/<0.001). The subjective image quality
      was rated significantly inferior only in segment 8 (p = 0.001) compared to the
      control group. Artifacts by ventricular leads were found in 65% of the patients
      in segment 8 with non-diagnostic rating in 9 cases (18%). Atrial leads resulted
      in artifacts predominantly in segment 1 (45%) with non-diagnostic rating in only
      2 cases (4%). CONCLUSION: CCTA is feasible with slight restrictions for patients
      in the presence of implanted cardiac devices when current technique is used.

PMID- 29567629
TI  - Whole-brain volume alteration and its correlation with anxiety severity in
      patients with obsessive-compulsive disorder and generalized anxiety disorder.
AB  - PURPOSE: To evaluate the differential gray matter (GM) and white matter volume
      alterations between healthy controls and patients with obsessive-compulsive
      disorder (OCD) and generalized anxiety disorder (GAD) using voxel-based
      morphometry (VBM). METHOD: Patients with OCD and GAD, and healthy controls
      underwent MR. RESULTS: Patients with GAD showed significantly decreased GM volume
      in the medial prefrontal cortex (mPFC) compared with patients with OCD (p <
      0.001). The GM volumes of the mPFC in patients with GAD were negatively
      correlated with Hamilton Anxiety Rating Scales. CONCLUSION: Our findings indicate
      that the mPFC volume abnormality may be associated with anxiety disorder in
      patients with GAD rather than OCD.

PMID- 29567631
TI  - Interventional radiology: Role in the treatment of sarcomas.
AB  - In bone and soft tissue sarcomas (STS), surgery was to the only local curative
      treatment, but recently, radiation therapy and interventional radiology has
      evolved to potentially curative treatment, namely in small size tumours.
      Indication for local treatment in STS needs validation in multidisciplinary team.
      Most will agree on local treatment for single metastatic location in a well
      controlled disease and for no local treatment in a rapidly evolving multi
      metastatic disease. The challenge is in patients who are in between, for whom
      benefit of disease control on overall survival should be evaluated. Local
      treatment has been reported beneficial in some large retrospective series,
      regardless of the association with chemotherapy in selected patients with
      oligometastatic disease. Recent technical innovation in image guidance allows to
      deliver local treatment through needles inserted percutaneously, and image-guided
      thermal ablation of small tumour is now part of the treatment armamentarium in
      selected oligometastatic diseases, allowing for local destruction of small
      tumour. Radiofrequency ablation allows to control small size STS lung metastases
      in roughly 90% of attempts, thus providing an efficient and low-invasive local
      control with preservation of organ function. Small size bone deposit can be
      targeted with the same rate of efficacy when tumours are small. Ablation can be
      used in the liver when some tumour foci become resistant to systemic therapy,
      namely in gastrointestinal stromal tumour patients. In addition, interventional
      radiology can now provide efficient and rapid pain palliation as well as bone
      reconstruction with the use of cementoplasty and percutaneous osteosynthesis,
      alongside radiation therapy which has been a long time player for pain palliation
      in bone metastases.

PMID- 29567632
TI  - The tyrosine kinase inhibitor crizotinib does not have clinically meaningful
      activity in heavily pre-treated patients with advanced alveolar rhabdomyosarcoma
      with FOXO rearrangement: European Organisation for Research and Treatment of
      Cancer phase 2 trial 90101 'CREATE'.
AB  - BACKGROUND: Alveolar rhabdomyosarcomas (ARMSs) can harbour MET and anaplastic
      lymphoma kinase (ALK) alterations. We prospectively assessed crizotinib in
      patients with advanced/metastatic ARMS. METHODS: Eligible patients with a central
      diagnosis of ARMS received oral crizotinib 250 mg twice daily. Patients were
      attributed to MET/ALK+ or MET/ALK- subcohorts by assessing the presence or
      absence of the forkhead box O1 (FOXO1; a marker of MET upregulation) and/or ALK
      gene rearrangement. The primary end-point was the objective response rate (ORR).
      Secondary end-points included duration of response (DOR), disease control rate
      (DCR), progression-free survival (PFS), progression-free rate (PFR), overall
      survival (OS) and safety. FINDINGS: Nineteen of 20 consenting patients had
      centrally confirmed ARMS. Molecular assessment revealed rearrangement of FOXO1 in
      17 tumours and ALK in none. Thirteen eligible patients were treated, but only
      eight were evaluable for the primary end-point because of the observed
      aggressiveness of the disease. Among seven evaluable MET+/ALK- patients, only one
      achieved a confirmed partial response (ORR: 14.3%; 95% confidence interval [CI]:
      0.3-57.8) with a DOR of 52 d. Further MET+/ALK- efficacy end-points were DCR:
      14.3% (95% CI: 0.3-57.8), median PFS: 1.3 months (95% CI: 0.5-1.5) and median OS:
      5.6 months (95% CI: 0.7-7.0). The remaining MET+/ALK- and MET-/ALK- patients had
      early progression as best response. Common treatment-related adverse events were
      fatigue (5/13 [38.5%]), nausea (4/13 [30.8%]), anorexia (4/13 [30.8%]), vomiting
      (2/13 [15.4%]) and constipation (2/13 [15.4%]). All 13 treated patients died
      early because of progressive disease. INTERPRETATION: Crizotinib is well
      tolerated but lacks clinically meaningful activity as a single agent in patients
      with advanced metastatic ARMS. Assessing single agents in aggressive,
      chemotherapy-refractory ARMS is challenging, and future trials should explore
      established chemotherapy +/- investigational compounds in earlier lines of
      treatment. CLINICAL TRIAL NUMBER: EORTC 90101, ClinicalTrials.gov NCT01524926.

PMID- 29567630
TI  - Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing
      two strategies for guiding prevention with enalapril: The International
      CardioOncology Society-one trial.
AB  - BACKGROUND: Troponin changes over time have been suggested to allow for an early
      diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with
      troponin elevation may benefit of therapy with enalapril. It is unknown whether a
      preventive treatment with enalapril may further increase the benefit. METHODS:
      The International CardioOncology Society-one trial (ICOS-ONE) was a controlled,
      open-label trial conducted in 21 Italian hospitals. Patients were randomly
      assigned to two strategies: enalapril in all patients started before chemotherapy
      (CT; 'prevention' arm), and enalapril started only in patients with an increase
      in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed
      locally in 2596 blood samples, before and after each anthracycline-containing CT
      cycle and at each study visit; electrocardiogram and echocardiogram were done at
      baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the
      incidence of troponin elevation above the threshold. FINDINGS: Of the 273
      patients, 88% were women, mean age 51 +/- 12 years. The majority (76%) had breast
      cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and
      doxorubicin were most commonly prescribed, with median cumulative doses of 360
      [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin
      elevation was 23% in the prevention and 26% in the troponin-triggered group (p =
      0.50). Three patients (1.1%) -two in the prevention, one in the troponin
      triggered group-developed cardiotoxicity, defined as 10% point reduction of LV
      ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative
      doses of anthracyclines in adult patients with low cardiovascular risk can raise
      troponins, without differences between the two strategies of giving enalapril.
      Considering a benefit of enalapril in the prevention of LV dysfunction, a
      troponin-triggered strategy may be more convenient.

PMID- 29567633
TI  - Web 2.0 Tools in the Prevention of Curable Sexually Transmitted Diseases: Scoping
      Review.
AB  - BACKGROUND: The internet is now the primary source of information that young
      people use to get information on issues related to sex, contraception, and
      sexually transmitted infections. OBJECTIVE: The goal of the research was to
      review the scientific literature related to the use of Web 2.0 tools as opposed
      to other strategies in the prevention of curable sexually transmitted diseases
      (STDs). METHODS: A scoping review was performed on the documentation indexed in
      the bibliographic databases MEDLINE, Cochrane Library, Scopus, Cumulative Index
      to Nursing and Allied Health Literature, Web of Science, Literatura
      Latinoamericana y del Caribe en Ciencias de la Salud, PsycINFO, Educational
      Resources Information Center, the databases of Centro Superior de Investigaciones
      Cientificas in Spain, and the Indice Bibliografico Espanol de Ciencias de la
      Salud from the first available date according to the characteristics of each
      database until April 2017. The equation search was realized by means of the using
      of descriptors together with the consultation of the fields of title register and
      summary with free terms. Bibliographies of the selected papers were searched for
      additional articles. RESULTS: A total of 627 references were retrieved, of which
      6 papers were selected after applying the inclusion and exclusion criteria. The
      STDs studied were chlamydia, gonorrhea, and syphilis. The Web 2.0 tools used were
      Facebook, Twitter, Instagram, and YouTube. The 6 papers used Web 2.0 in the
      promotion of STD detection. CONCLUSIONS: Web 2.0 tools have demonstrated a
      positive effect on the promotion of prevention strategies for STDs and can help
      attract and link youth to campaigns related to sexual health. These tools can be
      combined with other interventions. In any case, Web 2.0 and especially Facebook
      have all the potential to become essential instruments for public health.

PMID- 29567634
TI  - Standalone Effects of a Cognitive Behavioral Intervention Using a Mobile Phone
      App on Psychological Distress and Alcohol Consumption Among Japanese Workers:
      Pilot Nonrandomized Controlled Trial.
AB  - BACKGROUND: Research that investigates standalone effects of a mobile phone-based
      cognitive behavioral therapy without any human contact for reducing both
      psychological distress and risky drinking has been advancing; however, the number
      of studies is still limited. A mobile phone app called Self Record that
      facilitates cognitive restructuring through self-monitoring of daily thoughts and
      activities was developed in Japan. OBJECTIVE: This study conducted a
      nonrandomized controlled pilot trial of the Self Record app to investigate
      standalone effects of the intervention on psychological distress and alcohol
      consumption among Japanese workers. Additionally, we examined moderating effects
      of negative mood regulation expectancies, which are beliefs about one's ability
      to control one's negative mood. METHODS: A quasi-experimental design with a 1
      month follow-up was conducted online in Japan from February 2016 to March 2016. A
      research marketing company recruited participants. The selection criteria were
      being a Japanese full-time worker (age 20-59 years), experiencing mild to
      moderate psychological distress, and having some interest in self-record apps.
      Assignment to group was based on participants' willingness to use the app in the
      study. All participants completed outcome measures of negative mood regulation
      expectancies, positive well-being, general distress, depression, anxiety, and
      typical/most weekly alcohol consumption. RESULTS: From the recruitment, 15.65%
      (1083/6921) of participants met the inclusion criteria. Of these, 51.43%
      (557/1083) enrolled in the study: 54.9% (306/557) in the intervention group and
      45.1% (251/557) in the control group. At the 1-month follow-up, 15.3% (85/557) of
      participants had dropped out. Intention-to-treat analyses revealed that
      participants in the intervention group reported increased typical drinking
      (eta2=.009) and heavy drinking (eta2=.001). Adherence to using the app was low;
      64.8% (199/306) of participants in the intervention group discontinued using the
      app on the first day. Additionally, 65.7% (366/557) of the total sample did not
      correctly answer the validity checks in the outcome measures (eg, "Please select
      'mildly agree' for this item"). Therefore, per-protocol analyses were conducted
      after removing these participants. Results showed that continuing app users
      (42/127) in the intervention group reported increases in anxiety (eta2=.006),
      typical drinking (eta2=.005), and heavy drinking (eta2=.007) compared to those in
      the control group (85/127). Negative mood regulation expectancies moderated the
      effects of the intervention for general distress (beta=.39). CONCLUSIONS: Results
      were contrary to our hypotheses. Self-recording methods of standalone mobile
      phone interventions may heighten individuals' awareness of their pathological
      thought and drinking behavior, but may be insufficient to decrease them unless
      combined with a more intense or face-to-face intervention. Limitations include
      high attrition in this study; measures to improve the response rate are
      discussed.

PMID- 29567636
TI  - Pregnant Women Sharing Pregnancy-Related Information on Facebook: Web-Based
      Survey Study.
AB  - BACKGROUND: Research indicates expectant and new mothers use the Internet,
      specifically social media, to gain information and support during the transition
      to parenthood. Although parents regularly share information about and photos of
      their child or children on Facebook, researchers have neither explored the use of
      Facebook to share pregnancy-related information nor investigated factors that
      influence such sharing. OBJECTIVE: The aim of this study was to address a gap in
      the literature by exploring the use of Facebook by pregnant women. Specifically,
      the study examined the use of Facebook to share pregnancy-related information, as
      well as any association between prenatal attachment and the aforementioned
      aspects of sharing pregnancy-related information on Facebook. METHODS: Pregnant
      women who were at least 18 years of age were recruited for participation in the
      study through posts and paid advertisements on Facebook and posts to professional
      organization listservs. Individuals interested in participating were directed to
      a secure Web-based survey system where they completed the consent form and the
      survey that focused on their current pregnancy. Participants completed the
      Maternal Antenatal Attachment Scale and answered questions that assessed how
      often they shared pregnancy-related information on Facebook, who they shared it
      with, why they shared it, and what they shared. RESULTS: A total of 117 pregnant
      women completed the survey. Descriptive statistics indicated that the pregnancy
      announcement was most commonly shared (75/108, 69.4%), with most women sharing
      pregnancy-related information on Facebook less than monthly (52/117, 44.4%) with
      only family and friends (90/116, 77.6% and 91/116, 78.4%, respectively) and for
      the purpose of involving others or sharing the experience (62/107, 57.9%).
      Correlation and regression analyses showed that prenatal attachment, in general,
      was positively and significantly related to all aspects of sharing pregnancy
      related information at the P<.05 level, with the exception of sharing because of
      expectations. Quality of attachment, which involves the positive feelings the
      woman has about her unborn child, was significantly associated with sharing to
      involve others or share the pregnancy (t8,93=2.654 , P=.009). In contrast, after
      controlling for other variables, the strength or preoccupation component of
      prenatal attachment was significantly associated with frequency of sharing
      (t8,100=2.554 , P=.01), number to types of information shared (t8,97=2.605 ,
      P=.01), number of groups with whom shared (t8,99=3.467, P=.001), and sharing to
      get advice (chi28=5.339 , P=.02). CONCLUSIONS: Pregnant women in this study used
      Facebook for a variety of reasons, demonstrating the use of the social media
      platform during pregnancy for supportive and informational purposes. Overall, the
      results of this study are likely to be useful to professionals who are seeking
      alternative methods for providing intervention, information, and support to
      pregnant women via social media in our technology-driven society.

PMID- 29567635
TI  - Using Fitness Trackers and Smartwatches to Measure Physical Activity in Research:
      Analysis of Consumer Wrist-Worn Wearables.
AB  - BACKGROUND: New fitness trackers and smartwatches are released to the consumer
      market every year. These devices are equipped with different sensors, algorithms,
      and accompanying mobile apps. With recent advances in mobile sensor technology,
      privately collected physical activity data can be used as an addition to existing
      methods for health data collection in research. Furthermore, data collected from
      these devices have possible applications in patient diagnostics and treatment.
      With an increasing number of diverse brands, there is a need for an overview of
      device sensor support, as well as device applicability in research projects.
      OBJECTIVE: The objective of this study was to examine the availability of wrist
      worn fitness wearables and analyze availability of relevant fitness sensors from
      2011 to 2017. Furthermore, the study was designed to assess brand usage in
      research projects, compare common brands in terms of developer access to
      collected health data, and features to consider when deciding which brand to use
      in future research. METHODS: We searched for devices and brand names in six
      wearable device databases. For each brand, we identified additional devices on
      official brand websites. The search was limited to wrist-worn fitness wearables
      with accelerometers, for which we mapped brand, release year, and supported
      sensors relevant for fitness tracking. In addition, we conducted a Medical
      Literature Analysis and Retrieval System Online (MEDLINE) and ClinicalTrials
      search to determine brand usage in research projects. Finally, we investigated
      developer accessibility to the health data collected by identified brands.
      RESULTS: We identified 423 unique devices from 132 different brands. Forty-seven
      percent of brands released only one device. Introduction of new brands peaked in
      2014, and the highest number of new devices was introduced in 2015. Sensor
      support increased every year, and in addition to the accelerometer, a
      photoplethysmograph, for estimating heart rate, was the most common sensor. Out
      of the brands currently available, the five most often used in research projects
      are Fitbit, Garmin, Misfit, Apple, and Polar. Fitbit is used in twice as many
      validation studies as any other brands and is registered in ClinicalTrials
      studies 10 times as often as other brands. CONCLUSIONS: The wearable landscape is
      in constant change. New devices and brands are released every year, promising
      improved measurements and user experience. At the same time, other brands
      disappear from the consumer market for various reasons. Advances in device
      quality offer new opportunities for research. However, only a few well
      established brands are frequently used in research projects, and even less are
      thoroughly validated.

PMID- 29567637
TI  - Patient and Family Engagement in the Design of a Mobile Health Solution for
      Pediatric Asthma: Development and Feasibility Study.
AB  - BACKGROUND: Asthma is a highly prevalent, chronic disease with significant
      morbidity, cost, and disparities in health outcomes. While adherence to asthma
      treatment guidelines can improve symptoms and decrease exacerbations, most
      patients receive care that is not guideline-based. New approaches that
      incorporate shared decision-making (SDM) and health information technology (IT)
      are needed to positively impact asthma management. Despite the promise of health
      IT to improve efficiency and outcomes in health care, new IT solutions frequently
      suffer from a lack of widespread adoption and do not achieve desired results, as
      a consequence of not involving end-users in design. OBJECTIVE: To describe a case
      study of a pediatric asthma SDM health IT solution's development and demonstrate
      a methodology for engaging actual patients and families in IT development.
      Perspectives are shared from the vantage point of the research team and a parent
      of a child with asthma, who participated on the development team. METHODS: We
      adapted user-centric design principles to engage actual users across three main
      development phases: project initiation, ideation, and usability testing. To
      facilitate the necessary level of user engagement, our approach included: (1) a
      Development Workgroup consisting of patients, caregivers, and providers who met
      regularly with the research team; and (2) "real-world users" consisting of
      patients, caregivers, and providers recruited from a variety of care locations,
      including safety-net clinics. RESULTS: Using this methodology, we successful
      partnered with asthma patients and families to create an interactive, digital
      solution called Carolinas Asthma Coach. Carolinas Asthma Coach incorporates SDM
      principles to elicit patient information, including goals and preferences, and
      provides health-literate, tailored education with specific guideline-based
      recommendations for patients and their providers. Of the patients, caregivers,
      and providers surveyed, 100% (n=60) said they would recommend Carolinas Asthma
      Coach to a friend or colleague. Qualitative feedback from users provided support
      for the usability and engaging nature of the app. CONCLUSIONS: This project
      demonstrates the feasibility and benefits of deploying user-centric design
      methods that engage real patients and caregivers throughout the health IT design
      process.

PMID- 29567639
TI  - Costs of hospital bed and chair sensors include the time of healthcare workers
      monitoring them.

PMID- 29567638
TI  - Just-in-Time Feedback in Diet and Physical Activity Interventions: Systematic
      Review and Practical Design Framework.
AB  - BACKGROUND: The integration of body-worn sensors with mobile devices presents a
      tremendous opportunity to improve just-in-time behavioral interventions by
      enhancing bidirectional communication between investigators and their
      participants. This approach can be used to deliver supportive feedback at
      critical moments to optimize the attainment of health behavior goals. OBJECTIVE:
      The goals of this systematic review were to summarize data on the content
      characteristics of feedback messaging used in diet and physical activity (PA)
      interventions and to develop a practical framework for designing just-in-time
      feedback for behavioral interventions. METHODS: Interventions that included just
      in-time feedback on PA, sedentary behavior, or dietary intake were eligible for
      inclusion. Feedback content and efficacy data were synthesized descriptively.
      RESULTS: The review included 31 studies (15/31, 48%, targeting PA or sedentary
      behavior only; 13/31, 42%, targeting diet and PA; and 3/31, 10%, targeting diet
      only). All studies used just-in-time feedback, 30 (97%, 30/31) used personalized
      feedback, and 24 (78%, 24/31) used goal-oriented feedback, but only 5 (16%, 5/31)
      used actionable feedback. Of the 9 studies that tested the efficacy of providing
      feedback to promote behavior change, 4 reported significant improvements in
      health behavior. In 3 of these 4 studies, feedback was continuously available,
      goal-oriented, or actionable. CONCLUSIONS: Feedback that was continuously
      available, personalized, and actionable relative to a known behavioral objective
      was prominent in intervention studies with significant behavior change outcomes.
      Future research should determine whether all or some of these characteristics are
      needed to optimize the effect of feedback in just-in-time interventions.

PMID- 29567641
TI  - New insights into polycystic kidney disease.

PMID- 29567642
TI  - Economic Costs of Diabetes in the U.S. in 2017.
AB  - OBJECTIVE: This study updates previous estimates of the economic burden of
      diagnosed diabetes and quantifies the increased health resource use and lost
      productivity associated with diabetes in 2017. RESEARCH DESIGN AND METHODS: We
      use a prevalence-based approach that combines the demographics of the U.S.
      population in 2017 with diabetes prevalence, epidemiological data, health care
      cost, and economic data into a Cost of Diabetes Model. Health resource use and
      associated medical costs are analyzed by age, sex, race/ethnicity, insurance
      coverage, medical condition, and health service category. Data sources include
      national surveys, Medicare standard analytical files, and one of the largest
      claims databases for the commercially insured population in the U.S. RESULTS: The
      total estimated cost of diagnosed diabetes in 2017 is $327 billion, including
      $237 billion in direct medical costs and $90 billion in reduced productivity. For
      the cost categories analyzed, care for people with diagnosed diabetes accounts
      for 1 in 4 health care dollars in the U.S., and more than half of that
      expenditure is directly attributable to diabetes. People with diagnosed diabetes
      incur average medical expenditures of ~$16,750 per year, of which ~$9,600 is
      attributed to diabetes. People with diagnosed diabetes, on average, have medical
      expenditures ~2.3 times higher than what expenditures would be in the absence of
      diabetes. Indirect costs include increased absenteeism ($3.3 billion) and reduced
      productivity while at work ($26.9 billion) for the employed population, reduced
      productivity for those not in the labor force ($2.3 billion), inability to work
      because of disease-related disability ($37.5 billion), and lost productivity due
      to 277,000 premature deaths attributed to diabetes ($19.9 billion). CONCLUSIONS:
      After adjusting for inflation, economic costs of diabetes increased by 26% from
      2012 to 2017 due to the increased prevalence of diabetes and the increased cost
      per person with diabetes. The growth in diabetes prevalence and medical costs is
      primarily among the population aged 65 years and older, contributing to a growing
      economic cost to the Medicare program. The estimates in this article highlight
      the substantial financial burden that diabetes imposes on society, in addition to
      intangible costs from pain and suffering, resources from care provided by nonpaid
      caregivers, and costs associated with undiagnosed diabetes.

PMID- 29567640
TI  - Developing in 3D: the role of CTCF in cell differentiation.
AB  - CTCF is a highly conserved zinc-finger DNA-binding protein that mediates
      interactions between distant sequences in the genome. As a consequence, CTCF
      regulates enhancer-promoter interactions and contributes to the three-dimensional
      organization of the genome. Recent studies indicate that CTCF is developmentally
      regulated, suggesting that it plays a role in cell type-specific genome
      organization. Here, we review these studies and discuss how CTCF functions during
      the development of various cell and tissue types, ranging from embryonic stem
      cells and gametes, to neural, muscle and cardiac cells. We propose that the
      lineage-specific control of CTCF levels, and its partnership with lineage
      specific transcription factors, allows for the control of cell type-specific gene
      expression via chromatin looping.

PMID- 29567644
TI  - Paligenosis: prepare to regenerate!

PMID- 29567643
TI  - Structural centrosome aberrations promote non-cell-autonomous invasiveness.
AB  - Centrosomes are the main microtubule-organizing centers of animal cells. Although
      centrosome aberrations are common in tumors, their consequences remain subject to
      debate. Here, we studied the impact of structural centrosome aberrations, induced
      by deregulated expression of ninein-like protein (NLP), on epithelial spheres
      grown in Matrigel matrices. We demonstrate that NLP-induced structural centrosome
      aberrations trigger the escape ("budding") of living cells from epithelia.
      Remarkably, all cells disseminating into the matrix were undergoing mitosis. This
      invasive behavior reflects a novel mechanism that depends on the acquisition of
      two distinct properties. First, NLP-induced centrosome aberrations trigger a re
      organization of the cytoskeleton, which stabilizes microtubules and weakens E
      cadherin junctions during mitosis. Second, atomic force microscopy reveals that
      cells harboring these centrosome aberrations display increased stiffness. As a
      consequence, mitotic cells are pushed out of mosaic epithelia, particularly if
      they lack centrosome aberrations. We conclude that centrosome aberrations can
      trigger cell dissemination through a novel, non-cell-autonomous mechanism,
      raising the prospect that centrosome aberrations contribute to the dissemination
      of metastatic cells harboring normal centrosomes.

PMID- 29567646
TI  - Our humanity contains multitudes: Dehumanization is more than overlooking mental
      capacities.

PMID- 29567645
TI  - PTRN-1/CAMSAP promotes CYK-1/formin-dependent actin polymerization during
      endocytic recycling.
AB  - Cargo sorting and membrane carrier initiation in recycling endosomes require
      appropriately coordinated actin dynamics. However, the mechanism underlying the
      regulation of actin organization during recycling transport remains elusive. Here
      we report that the loss of PTRN-1/CAMSAP stalled actin exchange and diminished
      the cytosolic actin structures. Furthermore, we found that PTRN-1 is required for
      the recycling of clathrin-independent cargo hTAC-GFP The N-terminal calponin
      homology (CH) domain and central coiled-coils (CC) region of PTRN-1 can
      synergistically sustain the flow of hTAC-GFP We identified CYK-1/formin as a
      binding partner of PTRN-1. The N-terminal GTPase-binding domain (GBD) of CYK-1
      serves as the binding interface for the PTRN-1 CH domain. The presence of the
      PTRN-1 CH domain promoted CYK-1-mediated actin polymerization, which suggests
      that the PTRN-1-CH:CYK-1-GBD interaction efficiently relieves autoinhibitory
      interactions within CYK-1. As expected, the overexpression of the CYK-1 formin
      homology domain 2 (FH2) substantially restored actin structures and partially
      suppressed the hTAC-GFP overaccumulation phenotype in ptrn-1 mutants. We conclude
      that the PTRN-1 CH domain is required to stimulate CYK-1 to facilitate actin
      dynamics during endocytic recycling.

PMID- 29567648
TI  - A tough one to swallow.

PMID- 29567647
TI  - Increased liver tumor formation in neutral sphingomyelinase-2-deficient mice.
AB  - Sphingolipids are key signaling lipids in cancer. Genome-wide studies have
      identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a
      potential repressor for hepatocellular carcinoma. However, little is known about
      the sphingolipids regulated by nSMase2 and their roles in liver tumor
      development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33)
      of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a
      marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with
      more than a 7-fold increase of C16-ceramide, concurrent with upregulation of
      ceramide synthase 5. The fro/fro liver tumor, but not adjacent tissue, exhibited
      substantial accumulation of lipid droplets, suggesting that nSMase2 deficiency is
      associated with tumor growth and increased neutral lipid generation in the tumor.
      Tumor tissue expressed significantly increased levels of CD133 and EpCAM mRNA,
      two markers of liver cancer stem-like cells (CSCs) and higher levels of
      phosphorylated signal transducer and activator of transcription 3, an essential
      regulator of stemness. CD133(+) cells showed strong labeling for SM and ceramide.
      In conclusion, these results suggest that SMase-2 deficiency plays a role in the
      survival or proliferation of CSCs, leading to spontaneous tumors, which is
      associated with tumor-specific effects on lipid homeostasis.

PMID- 29567649
TI  - Triage in the Angiography Suite for Mechanical Thrombectomy in Acute Ischemic
      Stroke: Not Such a Good Idea.

PMID- 29567650
TI  - The New Low-Profile WEB 17 System for Treatment of Intracranial Aneurysms: First
      Clinical Experiences.
AB  - BACKGROUND AND PURPOSE: The Woven EndoBridge (WEB) is an intrasaccular flow
      diverter intended to treat wide-neck aneurysms. The latest generation WEBs needed
      a 0.021-inch microcatheter in the small sizes. Recently, a lower profile range of
      WEBs compliant with a 0.017-inch microcatheter (WEB 17) has been introduced. We
      present the first clinical results of treatment of both ruptured and unruptured
      aneurysms with the WEB 17. MATERIALS AND METHODS: Between December 2016 and
      September 2017, forty-six aneurysms in 40 patients were treated with the WEB 17.
      No supporting stents or balloons were used. Twenty-five aneurysms were ruptured
      (54%). There were 6 men and 34 women (mean age, 62 years; median, 63 years;
      range, 46-87 years). The mean aneurysm size was 4.9 mm (median, 5 mm; range, 2-7
      mm). RESULTS: There were 2 thromboembolic procedural complications without
      clinical sequelae and no ruptures. The overall permanent procedural complication
      rate was 0% (0 of 40; 97.5% CI, 0%-10.4%). Imaging follow-up at 3 months was
      available in 33 patients with 39 aneurysms (97.5% of 40 eligible aneurysms). In 1
      aneurysm, the detached WEB was undersized and the remnant was additionally
      treated with coils after 1 week. This same aneurysm reopened at 3 months and was
      again treated with a second WEB. One other aneurysm showed persistent WEB filling
      at 3 months. Complete occlusion was achieved in 28 of 39 aneurysms (72%), and 9
      aneurysms (23%) showed a neck remnant. CONCLUSIONS: The WEB 17 is safe and
      effective for both ruptured and unruptured aneurysms. The WEB 17 is a valuable
      addition to the existing WEB size range, especially for very small aneurysms.

PMID- 29567651
TI  - Brain MRI Characteristics of Patients with Anti-N-Methyl-D-Aspartate Receptor
      Encephalitis and Their Associations with 2-Year Clinical Outcome.
AB  - BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspertate receptor encephalitis is an
      autoimmune-mediated disease without specific brain MRI features. Our aim was to
      investigate the brain MR imaging characteristics of anti-N-methyl-D-aspartate
      receptor encephalitis and their associations with clinical outcome at a 2-year
      follow-up. MATERIALS AND METHODS: We enrolled 53 patients with anti-N-methyl-D
      aspartate receptor encephalitis and performed 2-year follow-up. Brain MRIs were
      acquired for all patients at the onset phase. The brain MR imaging manifestations
      were classified into 4 types: type 1: normal MR imaging findings; type 2: only
      hippocampal lesions; type 3: lesions not involving the hippocampus; and type 4:
      lesions in both the hippocampus and other brain areas. The modified Rankin Scale
      score at 2-year follow-up was assessed, and the association between the mRS and
      onset brain MR imaging characteristics was evaluated. RESULTS: Twenty-eight
      (28/53, 53%) patients had normal MR imaging findings (type 1), and the others
      (25/53, 47%) had abnormal MRI findings: type 2: 7 patients (13%); type 3: seven
      patients (13%); and type 4: eleven patients (21%). Normal brain MRI findings were
      more common in female patients (P = .02). Psychiatric and behavioral
      abnormalities were more common in adults (P = .015), and autonomic symptoms (P =
      .025) were more common in pediatric patients. The presence of hippocampal lesions
      (P = .008, OR = 9.584; 95% CI, 1.803-50.931) and relapse (P = .043, OR = 0.111;
      95% CI, 0.013-0.930) was associated with poor outcome. CONCLUSIONS: Normal brain
      MRI findings were observed in half of the patients. Lesions in the hippocampus
      were the most common MR imaging abnormal finding. The presence of hippocampal
      lesions is the main MR imaging predictor for poor prognosis in patients with anti
      N-methyl-D-aspartate receptor encephalitis.

PMID- 29567652
TI  - Transforaminal Lumbar Puncture: An Alternative Technique in Patients with
      Challenging Access.
AB  - Interlaminar lumbar puncture and cervical puncture may not be ideal in all
      circumstances. Recently, we have used a transforaminal approach in selected
      situations. Between May 2016 and December 2017, twenty-six transforaminal lumbar
      punctures were performed in 9 patients (25 CT-guided, 1 fluoroscopy-guided).
      Seven had spinal muscular atrophy and were referred for intrathecal nusinersen
      administration. In 2, CT myelography was performed via transforaminal lumbar
      puncture. The lumbar posterior elements were completely fused in 8, and there was
      an overlying abscess in 1. The L1-2 level was used in 2; the L2-3 level, in 10;
      the L3-4 level, in 12; and the L4-5 level, in 2 procedures. Post-lumbar puncture
      headache was observed on 4 occasions, which resolved without blood patching. One
      patient felt heat and pain at the injection site that resolved spontaneously
      within hours. One patient had radicular pain that resolved with conservative
      treatment. Transforaminal lumbar puncture may become an effective alternative to
      classic interlaminar lumbar puncture or cervical puncture.

PMID- 29567653
TI  - Diagnosing Early Ischemic Changes with the Latest-Generation Flat Detector CT: A
      Comparative Study with Multidetector CT.
AB  - BACKGROUND AND PURPOSE: One-stop management of mechanical thrombectomy-eligible
      patients with large-vessel occlusion represents an innovative approach in acute
      stroke treatment. This approach reduces door-to-reperfusion times by omitting
      multidetector CT, using flat detector CT as pre-mechanical thrombectomy imaging.
      The purpose of this study was to compare the diagnostic performance of the latest
      generation flat detector CT with multidetector CT. MATERIALS AND METHODS:
      Prospectively derived data from patients with ischemic stroke with large-vessel
      occlusion and mechanical thrombectomy were analyzed in this monocentric study.
      All included patients underwent multidetector CT before referral to our
      comprehensive stroke center and flat detector CT in the angiography suite before
      mechanical thrombectomy. Diagnosis of early ischemic signs, quantified by the
      ASPECTS, was compared between modalities using cross tables, the Pearson
      correlation, and Bland-Altman plots. The predictive value of multidetector CT-
      and flat detector CT-derived ASPECTS for functional outcome was investigated
      using area under the receiver operating characteristic curve analysis. RESULTS:
      Of 25 patients, 24 (96%) had flat detector CT with sufficient diagnostic quality.
      Median multidetector CT and flat detector CT ASPECTSs were 7 (interquartile
      range, 5.5-9 and 4.25-8, respectively) with a mean period of 143.6 +/- 49.5
      minutes between both modalities. The overall sensitivity was 85.1% and
      specificity was 83.1% for flat detector CT ASPECTS compared with multidetector CT
      ASPECTS as the reference technique. Multidetector CT and flat detector CT ASPECTS
      were strongly correlated (r = 0.849, P < .001) and moderately predicted
      functional outcome (area under the receiver operating characteristic curve,
      0.738; P = .007 and .715; P = .069, respectively). CONCLUSIONS: Determination of
      ASPECTS on flat detector CT is feasible, showing no significant difference
      compared with multidetector CT ASPECTS and a similar predictive value for
      functional outcome. Our findings support the use of flat detector CT for
      emergency stroke imaging before mechanical thrombectomy to reduce door-to-groin
      time.

PMID- 29567654
TI  - Endovascular Management of Acute Stroke in the Elderly: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Acute ischemic stroke occurs more frequently, presents with more
      severe symptoms, and has worse outcomes in elderly patients. The safety and
      efficacy of endovascular therapy for acute stroke in this age group has not been
      fully established. PURPOSE: We present the results of a systematic review and
      meta-analysis examining clinical, procedural, and radiologic outcomes of
      endovascular therapy for acute stroke in patients older than 80 years of age.
      DATA SOURCES: We searched PubMed, MEDLINE, and EMBASE from 1992 to week 35 of
      2017 for studies evaluating endovascular therapy for acute stroke in the elderly.
      STUDY SELECTION: Two independent reviewers selected studies and abstracted data.
      The primary end point was good functional outcome at 3 months defined as modified
      Rankin Scale score of <=2. DATA ANALYSIS: Data were analyzed using random-effects
      meta-analysis. DATA SYNTHESIS: Seventeen studies reporting on 860 patients were
      included. The rate of good functional outcome at 3 months was 27% (95% CI, 21%
      32%). Mortality at 3 months was 34% (95% CI, 23%-44%). Successful recanalization
      was achieved in 78% of patients (95% CI, 72%-85%). Procedure-related
      complications occurred in 11% (95% CI, 4%-17%). The incidence of intracranial
      hemorrhage was 24% (95% CI, 15%-32%), and for symptomatic intracranial
      hemorrhage, it was 8% (95% CI, 5%-10%). The mean time to groin was 251 minutes
      (95% CI, 224-278 minutes). Procedure time was 99 minutes (95% CI, 67-131
      minutes). LIMITATIONS: I2 values were above 50% for all outcomes, indicating
      substantial heterogeneity. CONCLUSIONS: Good functional recovery in octogenarians
      treated with endovascular therapy for acute stroke can be achieved in a high
      proportion of patients despite the higher incidence of comorbidity in this
      cohort. Outcomes are inferior to those reported for younger patients; however,
      endovascular therapy can allow at least 1 in 4 patients older than 80 years of
      age to regain independent function at 3 months. More research is required to
      improve patient selection in the elderly, but age should not be a discriminator
      when deciding to offer endovascular therapy for patients with acute stroke.

PMID- 29567655
TI  - 3D Deep Learning Angiography (3D-DLA) from C-arm Conebeam CT.
AB  - BACKGROUND AND PURPOSE: Deep learning is a branch of artificial intelligence that
      has demonstrated unprecedented performance in many medical imaging applications.
      Our purpose was to develop a deep learning angiography method to generate 3D
      cerebral angiograms from a single contrast-enhanced C-arm conebeam CT acquisition
      in order to reduce image artifacts and radiation dose. MATERIALS AND METHODS: A
      set of 105 3D rotational angiography examinations were randomly selected from an
      internal data base. All were acquired using a clinical system in conjunction with
      a standard injection protocol. More than 150 million labeled voxels from 35
      subjects were used for training. A deep convolutional neural network was trained
      to classify each image voxel into 3 tissue types (vasculature, bone, and soft
      tissue). The trained deep learning angiography model was then applied for tissue
      classification into a validation cohort of 8 subjects and a final testing cohort
      of the remaining 62 subjects. The final vasculature tissue class was used to
      generate the 3D deep learning angiography images. To quantify the generalization
      error of the trained model, we calculated the accuracy, sensitivity, precision,
      and Dice similarity coefficients for vasculature classification in relevant
      anatomy. The 3D deep learning angiography and clinical 3D rotational angiography
      images were subjected to a qualitative assessment for the presence of intersweep
      motion artifacts. RESULTS: Vasculature classification accuracy and 95% CI in the
      testing dataset were 98.7% (98.3%-99.1%). No residual signal from osseous
      structures was observed for any 3D deep learning angiography testing cases except
      for small regions in the otic capsule and nasal cavity compared with 37% (23/62)
      of the 3D rotational angiographies. CONCLUSIONS: Deep learning angiography
      accurately recreated the vascular anatomy of the 3D rotational angiography
      reconstructions without a mask. Deep learning angiography reduced misregistration
      artifacts induced by intersweep motion, and it reduced radiation exposure
      required to obtain clinically useful 3D rotational angiography.

PMID- 29567656
TI  - Cerebellar Growth Impairment Characterizes School-Aged Children Born Preterm
      without Perinatal Brain Lesions.
AB  - BACKGROUND AND PURPOSE: Infants born preterm are commonly diagnosed with
      structural brain lesions known to affect long-term neurodevelopment negatively.
      Yet, the effects of preterm birth on brain development in the absence of
      intracranial lesions remain to be studied in detail. In this study, we aim to
      quantify long term consequences of preterm birth on brain development in this
      specific group. MATERIALS AND METHODS: Neonatal cranial sonography and follow-up
      T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic
      characteristics of the cerebrum and cerebellum in a cohort of school-aged
      children (6-12 years of age) were related to gestational age at birth in children
      free of brain lesions in the perinatal period. RESULTS: In the cohort consisting
      of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1
      weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar
      white matter volume (beta = 0.387, P < .001), altered fractional anisotropy of
      cerebellar white matter (beta = -0.236, P = .02), and a reduction of cerebellar
      gray and white matter surface area (beta = 0.337, P < .001; beta = 0.375, P <
      .001, respectively) in relation to birth age. Such relations were not observed
      for the cerebral cortex or white matter volume, surface area, or diffusion
      quantities. CONCLUSIONS: The results of our study show that perinatal influences
      that are not primarily neurologic are still able to disturb long-term
      neurodevelopment, particularly of the developing cerebellum. Including the
      cerebellum in future neuroprotective strategies seems therefore essential.

PMID- 29567657
TI  - Factors Influencing Confidence in Diagnostic Ratings and Retreatment
      Recommendations in Coiled Aneurysms.
AB  - BACKGROUND AND PURPOSE: Angiographic occlusion and retreatment of coiled
      aneurysms are commonly used as surrogate end points in clinical trials. We aimed
      to evaluate the influence of aneurysm, patient, and rater characteristics on the
      confidence of visual evaluation of aneurysm coiling and retreatment decisions.
      MATERIALS AND METHODS: Twenty-six participants of the Advanced Course in
      Endovascular Interventional Neuroradiology of the European Society of
      Neuroradiology were asked to evaluate digital subtraction angiography
      examinations of patients who had undergone endovascular coiling, by determining
      the grade of aneurysm occlusion, the change between immediate postprocedural and
      follow-up angiograms, their level of confidence, the technical difficulty of
      retreatment, and the best therapeutic approach. The experience, knowledge, and
      skills of each participant were assessed. The influence of rater and case
      characteristics on indicated confidence in diagnostic ratings and retreatment
      recommendations was analyzed. RESULTS: Interrater reliability was moderate
      regarding the assessment of aneurysm occlusion grade (intraclass correlation
      coefficient = 0.581) and substantial regarding change (intraclass correlation
      coefficient = 0.776). Overall confidence in the diagnostic rating was high
      (median, "very certain"). Confidence was statistically significantly higher in
      cases that were generally rated as "worse." The odds of recommending retreatment
      were significantly higher in cases that were generally rated with higher mean
      confidence. CONCLUSIONS: Although overall confidence in the diagnostic rating was
      high, our study confirms the suboptimal interrater reliability of visual
      assessment of aneurysm occlusion as well as retreatment recommendations,
      rendering both questionable as primary outcome measures. Besides recurrence
      status, recommendation of retreatment is significantly influenced by patient age,
      aneurysm neck width, and characteristics of the therapist.

PMID- 29567660
TI  - Noninvasive Detection of Cocaine and Heroin Use with Single Fingerprints:
      Determination of an Environmental Cutoff.
AB  - BACKGROUND: Recent publications have explored the possibility of using
      fingerprints to confirm drug use, but none has yet dealt with environmental
      contamination from fingertips. Here we explored the possibility of establishing
      an environmental cutoff for drug testing from a single fingerprint. METHODS:
      Fingerprint samples (n = 100) were collected from the hands of 50 nondrug users
      before and after handwashing to establish separate environmental cutoff values
      and testing protocols for cocaine, benzoylecgonine, heroin, and 6
      monoacetylmorphine. The cutoff was challenged by testing the fingerprints of drug
      free volunteers after shaking hands with drug users. Fingerprints from patients
      who testified to taking cocaine (n = 32) and heroin (n = 24) were also collected
      and analyzed. RESULTS: A different cutoff value needed to be applied, depending
      on whether the fingerprints were collected as presented or after handwashing.
      Applying these cutoffs gave a 0% false-positive rate from the drug-free
      volunteers. After application of the cutoff, the detection rate (compared to
      patient testimony) for washed hands of patients was 87.5% for cocaine use and
      100% for heroin use. CONCLUSIONS: Fingerprints show enhanced levels of cocaine,
      heroin, and their respective metabolites in patients who testified to taking the
      substances, compared with the population of naive drug users surveyed, and a
      cutoff (decision level) can be established. The cutoff is robust enough to
      account for small increases in analyte observed after secondary transfer.

PMID- 29567658
TI  - Establishment of Signaling Interactions with Cellular Resolution for Every Cell
      Cycle of Embryogenesis.
AB  - Intercellular signaling interactions play a key role in breaking fate symmetry
      during animal development. Identification of signaling interactions at cellular
      resolution is technically challenging, especially in a developing embryo. Here,
      we develop a platform that allows automated inference and validation of signaling
      interactions for every cell cycle of Caenorhabditis elegans embryogenesis. This
      is achieved by the generation of a systems-level cell contact map, which consists
      of 1114 highly confident intercellular contacts, by modeling analysis and is
      validated through cell membrane labeling coupled with cell lineage analysis. We
      apply the map to identify cell pairs between which a Notch signaling interaction
      takes place. By generating expression patterns for two ligands and two receptors
      of the Notch signaling pathway with cellular resolution using the automated
      expression profiling technique, we are able to refine existing and identify novel
      Notch interactions during C. elegans embryogenesis. Targeted cell ablation
      followed by cell lineage analysis demonstrates the roles of signaling
      interactions during cell division in breaking fate symmetry. Finally, we describe
      the development of a website that allows online access to the cell-cell contact
      map for mapping of other signaling interactions by the community. The platform
      can be adapted to establish cellular interactions from any other signaling
      pathway.

PMID- 29567661
TI  - Quality Control of Serum and Plasma by Quantification of (4E,14Z)-Sphingadienine
      C18-1-Phosphate Uncovers Common Preanalytical Errors During Handling of Whole
      Blood.
AB  - BACKGROUND: Nonadherence to standard operating procedures (SOPs) during handling
      and processing of whole blood is one of the most frequent causes affecting the
      quality of serum and plasma. Yet, the quality of blood samples is of the utmost
      importance for reliable, conclusive research findings, valid diagnostics, and
      appropriate therapeutic decisions. METHODS: UHPLC-MS-driven nontargeted
      metabolomics was applied to identify biomarkers that reflected time to processing
      of blood samples, and a targeted UHPLC-MS analysis was used to quantify and
      validate these biomarkers. RESULTS: We found that (4E,14Z)-sphingadienine-C18-1
      phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced
      changes in the quality of serum and plasma caused by errors in the phase between
      collection and centrifugation of whole blood samples. We rigorously validated S1P
      d18:2, which included the use of practicality tests on >1400 randomly selected
      serum and plasma samples that were originally collected during single- and
      multicenter trials and then stored in 11 biobanks in 3 countries. Neither life
      threatening disease states nor strenuous metabolic challenges (i.e., high
      intensity exercise) affected the concentration of S1P-d18:2. Cutoff values for
      sample assessment were defined (plasma, <=0.085 MUg/mL; serum, <=0.154 MUg/mL).
      CONCLUSIONS: Unbiased valid monitoring to check for adherence to SOP-dictated
      time for processing to plasma or serum and/or time to storage of whole blood at 4
      degrees C is now feasible. This novel quality assessment step could enable
      scientists to uncover common preanalytical errors, allowing for identification of
      serum and plasma samples that should be excluded from certain investigations. It
      should also allow control of samples before long-term storage in biobanks.

PMID- 29567659
TI  - Genetic Drivers of Pancreatic Islet Function.
AB  - The majority of gene loci that have been associated with type 2 diabetes play a
      role in pancreatic islet function. To evaluate the role of islet gene expression
      in the etiology of diabetes, we sensitized a genetically diverse mouse population
      with a Western diet high in fat (45% kcal) and sucrose (34%) and carried out
      genome-wide association mapping of diabetes-related phenotypes. We quantified
      mRNA abundance in the islets and identified 18,820 expression QTL. We applied
      mediation analysis to identify candidate causal driver genes at loci that affect
      the abundance of numerous transcripts. These include two genes previously
      associated with monogenic diabetes (PDX1 and HNF4A), as well as three genes with
      nominal association with diabetes-related traits in humans (FAM83E, IL6ST, and
      SAT2). We grouped transcripts into gene modules and mapped regulatory loci for
      modules enriched with transcripts specific for alpha-cells, and another specific
      for delta-cells. However, no single module enriched for beta-cell-specific
      transcripts, suggesting heterogeneity of gene expression patterns within the beta
      cell population. A module enriched in transcripts associated with branched-chain
      amino acid metabolism was the most strongly correlated with physiological traits
      that reflect insulin resistance. Although the mice in this study were not overtly
      diabetic, the analysis of pancreatic islet gene expression under dietary-induced
      stress enabled us to identify correlated variation in groups of genes that are
      functionally linked to diabetes-associated physiological traits. Our analysis
      suggests an expected degree of concordance between diabetes-associated loci in
      the mouse and those found in human populations, and demonstrates how the mouse
      can provide evidence to support nominal associations found in human genome-wide
      association mapping.

PMID- 29567662
TI  - Wheat miR9678 Affects Seed Germination by Generating Phased siRNAs and Modulating
      Abscisic Acid/Gibberellin Signaling.
AB  - Seed germination is important for grain yield and quality and rapid, near
      simultaneous germination helps in cultivation; however, cultivars that germinate
      too readily can undergo preharvest sprouting (PHS), which causes substantial
      losses in areas that tend to get rain around harvest time. Moreover, our
      knowledge of mechanisms regulating seed germination in wheat (Triticum aestivum)
      remains limited. In this study, we analyzed function of a wheat-specific microRNA
      9678 (miR9678), which is specifically expressed in the scutellum of developing
      and germinating seeds. Overexpression of miR9678 delayed germination and improved
      resistance to PHS in wheat through reducing bioactive gibberellin (GA) levels;
      miR9678 silencing enhanced germination rates. We provide evidence that miR9678
      targets a long noncoding RNA (WSGAR) and triggers the generation of phased small
      interfering RNAs that play a role in the delay of seed germination. Finally, we
      found that abscisic acid (ABA) signaling proteins bind the promoter of miR9678
      precursor and activate its expression, indicating that miR9678 affects
      germination by modulating the GA/ABA signaling.

PMID- 29567663
TI  - The Ubiquitin E3 Ligase PRU1 Regulates WRKY6 Degradation to Modulate Phosphate
      Homeostasis in Response to Low-Pi Stress in Arabidopsis.
AB  - Since phosphorus is an essential nutrient for plants, plants have evolved a
      number of adaptive mechanisms to respond to changes in phosphate (Pi) supply.
      Previously, we reported that the transcription factor WRKY6 modulates Pi
      homeostasis by downregulating PHOSPHATE1 (PHO1) expression and that WRKY6 is
      degraded during Pi starvation in Arabidopsis thaliana However, the molecular
      mechanism underlying low-Pi-induced WRKY6 degradation was unknown. Here, we
      report that a ubiquitin E3 ligase, PHOSPHATE RESPONSE UBIQUITIN E3 LIGASE1
      (PRU1), modulates WRKY6 protein levels in response to low-Pi stress. A pru1
      mutant was more sensitive than the wild type to Pi-deficient conditions,
      exhibiting a reduced Pi contents in the shoot, similar to the pho1-2 mutant and
      WRKY6-overexpressing line. PRU1 interacted with WRKY6 in vitro and in vivo. Under
      low-Pi stress, the ubiquitination and subsequent degradation of WRKY6, as well as
      the consequential enhancement of PHO1 expression, were impaired in pru1 PRU1
      complementation lines displayed no obvious differences compared with wild-type
      plants. Further genetic analysis showed that disruption of WRKY6 abolished the
      low-Pi sensitivity of pru1, indicating that WRKY6 functioned downstream of PRU1.
      Taken together, this study uncovers a mechanism by which PRU1 modulates Pi
      homeostasis, through regulating the abundance of WRKY6 in response to low-Pi
      stress in Arabidopsis.

PMID- 29567664
TI  - Acceptability of a parental early warning tool for parents of infants with
      complex congenital heart disease: a qualitative feasibility study.
AB  - AIM: To explore the acceptability and feasibility of a parental early warning
      tool, called the Congenital Heart Assessment Tool (CHAT), for parents going home
      with their infant between first and second stage of surgery for complex
      congenital heart disease. BACKGROUND: Home monitoring programmes were developed
      to aid early recognition of deterioration in fragile infants between first and
      second surgical stage. However, this necessitates good discharge preparation to
      enable parents to develop appropriate knowledge and understanding of signs of
      deterioration to look for and who to contact. DESIGN: This was a longitudinal
      qualitative feasibility study, within a constructivist paradigm. Parents were
      taught how to use the CHAT before taking their infant home and asked to
      participate in semistructured interviews at four time points: before discharge
      (T0), 2 weeks after discharge (T1), 8 weeks after discharge (T2) and after stage
      2 surgery (T3). Interviews were transcribed verbatim and thematically analysed.
      SETTING: One tertiary children's cardiac centre in the UK. SUBJECTS: Twelve
      parents of eight infants who were discharged following first stage cardiac
      surgery for complex congenital heart disease, between August 2013 and February
      2015. RESULTS: Four main themes emerged: (1) parental preparation and vigilance,
      (2) usability, (3) mastery, and (4) reassurance and support. CONCLUSIONS: The
      study highlighted the benefit of appropriately preparing parents before
      discharge, using the CHAT, to enable identification of normal infant behaviour
      and to detect signs of clinical deterioration. The study also demonstrated the
      importance of providing parents with information about when and who to call for
      management advice and support.

PMID- 29567665
TI  - Paediatric Ebstein's anomaly: how clinical presentation predicts mortality.
AB  - BACKGROUND: Forecasting the prognosis of a child when diagnosed with Ebstein's
      anomaly is difficult. We, therefore, studied which factors at the time of
      diagnosis are associated with death during childhood. METHODS: All consecutive
      patients (0-18 years) diagnosed with Ebstein's anomaly in the Netherlands between
      1980 and 2014 were included. Survival curves were obtained using the Kaplan-Meier
      method. By using the Cox proportional hazard model, we analysed the factors (at
      diagnosis) that were associated with death. RESULTS: We included 176 patients.
      Thirty-one patients (18%) died before the age of 18 years. The 1-year survival
      was 84% and remained stable at 82% from 35 months after diagnosis and onwards.
      Modified Ross Heart Failure Class 4 at the time of diagnosis was the most
      important risk factor for death during childhood (HR 12.5, 95% CI 4.4 to 35.9).
      Furthermore, diagnosis in the neonatal period (HR 4.2, 95% CI 1.5 to 12.0),
      severe tricuspid valve regurgitation (HR 2.4, 95% CI 1.2 to 5.0), severe right
      ventricular outflow tract obstruction (HR 3.7, 95% CI 1.8 to 7.7) and a patent
      ductus arteriosus (HR 2.8, 95% CI 1.3 to 6.0) at the time of diagnosis were
      univariately associated with death. Multivariable analysis showed that
      presentation with Heart Failure Class 4 and a ventricular septal defect is the
      strongest predictor of death in childhood and adolescence. CONCLUSION: Patients
      with Ebstein's anomaly presenting with Heart Failure Class 4 and a ventricular
      septal defect have a high risk of death during childhood.

PMID- 29567666
TI  - Powerful effects of placebo needles.

PMID- 29567667
TI  - Dysfunctional cognition regarding sleep as a mediator of outcome following
      acupuncture for insomnia.

PMID- 29567668
TI  - Muscular diagnostics and the feasibility of microsystem acupuncture as a
      potential adjunct in the treatment of painful temporomandibular disorders:
      results of a retrospective cohort study.
AB  - AIMS: To investigate the effect of microsystem acupuncture on painful
      temporomandibular disorders (TMD). METHODS: We retrospectively analysed 887
      treatments in 407 TMD-patients (mean age 45+/-1.5 years), who received
      microsystem acupuncture (mouth, scalp or fingers) with a focus on oral
      acupuncture. All patients systematically underwent palpation of specific muscular
      tender points and their pain rating was assessed on a four-point Likert scale (no
      pain to strong pain) before and after treatment. In 42 cases, the pain intensity
      was determined using a visual analogue scale (0-100 mm). As the data were
      normally distributed, analysis was performed with unpaired t-tests. RESULTS: The
      pterygoid muscles were most painful to palpation, with the lateral pterygoid
      rated moderate to strong by 76% of patients and the medial pterygoid by 48% of
      patients. The palpation of microsystem acupuncture points revealed the strongest
      sensitivity (moderate or strong pain) of the oral retromolar points at the upper
      jaw (83%). After treatment, the pain intensity of all tender points had
      significantly decreased (P<0.001). The proportion of moderate to strong pain
      ratings was below 3% at most tender points. Overall pain intensity of the
      subjects (n=42) before treatment was 55.5+/-19.7 mm on the VAS scale and was
      significantly reduced to 29.6+/-20.9 mm (P<0.001) post-treatment. CONCLUSIONS:
      This analysis suggests microsystem acupuncture could reduce the pain intensity of
      TMD in the short term. Considering the increased local muscular tenderness,
      further investigations regarding the key role of myofascial trigger points in the
      occurrence of TMDs are warranted and could lead to new comprehensive treatment
      strategies.

PMID- 29567669
TI  - GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to
      Right-Left Type Bicuspid Aortic Valve.
AB  - BACKGROUND: Bicuspid aortic valve (BAV), the most common congenital heart defect
      affecting 1% to 2% of the population, is a major risk factor for premature aortic
      valve disease and accounts for the majority of valve replacement. The genetic
      basis and mechanisms of BAV etiology and pathogenesis remain largely undefined.
      METHODS: Cardiac structure and function was assessed in mice lacking a Gata6
      allele. Human GATA6 gene variants were analyzed in 452 BAV cases from the BAV
      consortium and 1849 controls from the Framingham GWAS (Genome Wide Association
      Study). GATA6 expression was determined in mice and human tissues using
      quantitative real-time polymerase chain reaction and immunohistochemistry.
      Mechanistic studies were carried out in cultured cells. RESULTS: Gata6
      heterozygous mice have highly penetrant right-left (RL)-type BAV, the most
      frequent type in humans. GATA6 transcript levels are lower in human BAV compared
      with normal tricuspid valves. Mechanistically, Gata6 haploinsufficiency disrupts
      valve remodeling and extracellular matrix composition through dysregulation of
      important signaling molecules, including matrix metalloproteinase 9. Cell
      specific inactivation of Gata6 reveals an essential role for GATA6 in secondary
      heart field myocytes because loss of 1 Gata6 allele from Isl- 1-positive cells
      but not from endothelial or neural crest cells-recapitulates the phenotype of
      Gata6 heterozygous mice. CONCLUSIONS: The data identify a new cellular and
      molecular mechanism underlying BAV. The availability of an animal model for the
      most frequent human BAV opens the way for the elucidation of BAV pathogenesis and
      the development of much needed therapies.

PMID- 29567670
TI  - Conserved functional control, but distinct regulation, of cell proliferation in
      rice and Arabidopsis leaves revealed by comparative analysis of GRF-INTERACTING
      FACTOR 1 orthologs.
AB  - Regulation of cell proliferation is crucial for establishing the shape of plant
      leaves. We have identified MAKIBA3 (MKB3), a loss-of-function mutant of which
      exhibits a narrowed- and rolled-leaf phenotype in rice. MKB3 was found to be an
      ortholog of Arabidopsis ANGUSTIFOLIA3 (AN3), which positively regulates cell
      proliferation. The reduced leaf size of mkb3 plants with enlarged cells and the
      increased size of MKB3-overexpressing leaves with normal-sized cells indicate
      that MKB3 is a positive regulator of leaf proliferation and that mkb3 mutation
      triggers a compensation syndrome, as does Arabidopsis an3 Expression analysis
      revealed that MKB3 is predominantly expressed on the epidermis of leaf primordia,
      which is different from the location of AN3 A protein movement assay demonstrated
      that MKB3 moves from an MKB3-expressing domain to a non-expressing domain, which
      is required for normal leaf development. Our results suggest that rice MKB3 and
      Arabidopsis AN3 have conserved functions and effects on leaf development.
      However, the expression pattern of MKB3 and direction of protein movement are
      different between rice and Arabidopsis, which might reflect differences in leaf
      primordia development in these two species.

PMID- 29567671
TI  - Control of the proportion of inner cells by asymmetric divisions and the ensuing
      resilience of cloned rabbit embryos.
AB  - Mammalian embryo cloning by nuclear transfer has a low success rate. This is
      hypothesized to correlate with a high variability of early developmental steps
      that segregate outer cells, which are fated to extra-embryonic tissues, from
      inner cells, which give rise to the embryo proper. Exploring the cell lineage of
      wild-type embryos and clones, imaged in toto until hatching, highlights the
      respective contributions of cell proliferation, death and asymmetric divisions to
      phenotypic variability. Preferential cell death of inner cells in clones,
      probably pertaining to the epigenetic plasticity of the transferred nucleus, is
      identified as a major difference with effects on the proportion of inner cell. In
      wild type and clones, similar patterns of outer cell asymmetric divisions are
      shown to be essential to the robust proportion of inner cells observed in wild
      type. Asymmetric inner cell division, which is not described in mice, is
      identified as a regulator of the proportion of inner cells and likely gives rise
      to resilient clones.

PMID- 29567672
TI  - Origin and specification of type II neuroblasts in the Drosophila embryo.
AB  - In Drosophila, neural stem cells or neuroblasts (NBs) acquire different
      identities according to their site of origin in the embryonic neuroectoderm.
      Their identity determines the number of times they will divide and the types of
      daughter cells they will generate. All NBs divide asymmetrically, with type I NBs
      undergoing self-renewal and generating another cell that will divide only once
      more. By contrast, a small set of NBs in the larval brain, type II NBs, divides
      differently, undergoing self-renewal and generating an intermediate neural
      progenitor (INP) that continues to divide asymmetrically several more times,
      generating larger lineages. In this study, we have analysed the origin of type II
      NBs and how they are specified. Our results indicate that these cells originate
      in three distinct clusters in the dorsal protocerebrum during stage 12 of
      embryonic development. Moreover, it appears that their specification requires the
      combined action of EGFR signalling and the activity of the related genes
      buttonhead and Drosophila Sp1 In addition, we also show that the INPs generated
      in the embryo enter quiescence at the end of embryogenesis, resuming
      proliferation during the larval stage.

PMID- 29567673
TI  - Medical union: the pathway to an efficient healthcare system in China.

PMID- 29567674
TI  - Whole-genome sequencing of Atacama skeleton shows novel mutations linked with
      dysplasia.
AB  - Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the
      Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in
      stature, fewer than expected ribs, elongated cranium, and accelerated bone age
      leading to speculation that this was a preserved nonhuman primate, human fetus
      harboring genetic mutations, or even an extraterrestrial. We previously reported
      that it was human by DNA analysis with an estimated bone age of about 6-8 yr at
      the time of demise. To determine the possible genetic drivers of the observed
      morphology, DNA from the specimen was subjected to whole-genome sequencing using
      the Illumina HiSeq platform with an average 11.5* coverage of 101-bp, paired-end
      reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as
      compared to the human reference genome, 518,365 insertions and deletions
      (indels), and 1047 structural variations (SVs) were detected. Here, we present
      the detailed whole-genome analysis showing that Ata is a female of human origin,
      likely of Chilean descent, and its genome harbors mutations in genes (COL1A1,
      COL2A1, KMT2D, FLNB, ATR, TRIP11, PCNT) previously linked with diseases of small
      stature, rib anomalies, cranial malformations, premature joint fusion, and
      osteochondrodysplasia (also known as skeletal dysplasia). Together, these
      findings provide a molecular characterization of Ata's peculiar phenotype, which
      likely results from multiple known and novel putative gene mutations affecting
      bone development and ossification.

PMID- 29567677
TI  - Parvins Are Required for Endothelial Cell-Cell Junctions and Cell Polarity During
      Embryonic Blood Vessel Formation.
AB  - OBJECTIVE: During vascular development, integrin-mediated signaling regulates the
      formation and stabilization of cell-cell junctions, which are required for
      endothelial cell (EC) apical-basal polarity and proper deposition of the vascular
      basement membrane. Parvins are actin-binding proteins that facilitate the
      interaction of integrins with the actin cytoskeleton. The endothelium expresses 2
      parvin isoforms: alpha-pv (alpha-parvin) and beta-pv (beta-parvin). Recently, we
      have shown that alpha-pv is critical for vessel growth and vessel stability at
      late embryonic developmental stages. The role of parvins during early embryonic
      development is unknown. APPROACH AND RESULTS: To investigate the role of
      endothelial parvins in the developing vasculature, we generated mice with ECs
      lacking both parvin isoforms by deleting alpha-pv in ECs in global beta-pv-/-
      mice (alpha-pvDeltaEC;beta-pv-/- mice). Here, we show that alpha-pvDeltaEC;beta
      pv-/- mice die around embryonic day 11.5 and exhibit hemorrhages, immature
      capillary beds, and severe vascular defects in the central nervous system,
      including reduced vessel branching, increased vessel diameter, and balloon-like
      hemorrhagic clusters of ECs. Vessels in alpha-pvDeltaEC;beta-pv-/- embryos
      display disorganized cell-cell junctions, impaired endothelial apical-basal
      polarity, and discontinuous basement membranes. These vascular defects are
      accompanied by defective pericyte-vessel interaction. CONCLUSIONS: Our results
      show that parvins are critical for the organization of endothelial cell-cell
      junctions, the establishment of endothelial apical-basal polarity, and the
      integrity of the basement membrane.

PMID- 29567675
TI  - Promoter architecture determines cotranslational regulation of mRNA.
AB  - Information that regulates gene expression is encoded throughout each gene but if
      different regulatory regions can be understood in isolation, or if they interact,
      is unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs)
      transcribed from either an inducible or constitutive promoter. We find that the
      strength of cotranslational regulation on mRNA levels is determined by promoter
      architecture. By using a novel computational genetic screen of 6402 RNA-seq
      experiments, we identify the RNA helicase Dbp2 as the mechanism by which
      cotranslational regulation is reduced specifically for inducible promoters.
      Finally, we find that for constitutive genes, but not inducible genes, most of
      the information encoding regulation of mRNA levels in response to changes in
      growth rate is encoded in the ORF and not in the promoter. Thus, the ORF sequence
      is a major regulator of gene expression, and a nonlinear interaction between
      promoters and ORFs determines mRNA levels.

PMID- 29567676
TI  - Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2
      induce myeloid malignancies via unique SNP-specific RNA mutations.
AB  - The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the
      accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have
      been implicated in cancer predisposition, although causality has not been
      established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate
      that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further
      identified that CCAT2 is overexpressed in bone marrow and peripheral blood of
      myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces
      global deregulation of gene expression by down-regulating EZH2 in vitro and in
      vivo in an allele-specific manner. We also identified a novel non-APOBEC, non
      ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice.
      The RNA transcribed from the SNP locus in malignant hematopoietic cells have
      different allelic composition from the corresponding genomic DNA, a phenomenon
      rarely observed in normal cells. Our findings provide fundamental insights into
      the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.

PMID- 29567678
TI  - Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by
      Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report.
AB  - OBJECTIVE: Aortic arch transplants have advanced our understanding of processes
      that contribute to progression and regression of atherosclerotic plaques. To
      characterize the dynamic behavior of monocytes and macrophages in atherosclerotic
      plaques over time, we developed a new model of cervical aortic arch
      transplantation in mice that is amenable to intravital imaging. APPROACH AND
      RESULTS: Vascularized aortic arch grafts were transplanted heterotropically to
      the right carotid arteries of recipient mice using microsurgical suture
      techniques. To image immune cells in atherosclerotic lesions during regression,
      plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted
      into syngeneic CX3CR1 GFP reporter mice. Grafts were evaluated histologically,
      and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were
      imaged intravitally by 2-photon microscopy in serial fashion. In complementary
      experiments, CCR2+ cells in plaques were serially imaged by positron emission
      tomography using specific molecular probes. Plaques in ApoE-deficient grafts
      underwent regression after transplantation into normolipidemic hosts. Intravital
      imaging revealed clusters of largely immotile CX3CR1+ monocytes/macrophages in
      regressing plaques that had been recruited from the periphery. We observed a
      progressive decrease in CX3CR1+ monocytic cells in regressing plaques and a
      decrease in CCR2+ positron emission tomography signal during 4 months.
      CONCLUSIONS: Cervical transplantation of atherosclerotic mouse aortic arches
      represents a novel experimental tool to investigate cellular mechanisms that
      contribute to the remodeling of atherosclerotic plaques.

PMID- 29567680
TI  - Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances
      Atherosclerosis.
AB  - OBJECTIVE: Cardiovascular diseases and depression are the leading causes of
      disability in Western countries. Clinical data on potential cardiovascular
      effects of serotonin reuptake inhibitors (SSRIs), the most commonly used
      antidepressant drugs, are controversial. In addition to blocking serotonin
      reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin
      (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter
      mediated uptake in platelets. In this study, we aimed to investigate the effect
      of chronic SSRI intake on the development of atherosclerosis. APPROACH AND
      RESULTS: Treatment of apolipoprotein E-deficient mice with the SSRI fluoxetine
      for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most
      pronounced effect during early plaque development. Intravital microscopy of
      carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment.
      Mechanistically, we found that fluoxetine augmented vascular permeability and
      increased chemokine-induced integrin-binding activity of circulating leukocytes.
      In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT,
      could directly promote beta1 and beta2 integrin activation provided C-C motif
      chemokine ligand 5 was also present. Similar effects were observed with the SSRI
      escitalopram. Enhanced C-C motif chemokine ligand 5-induced integrin activation
      by fluoxetine was also confirmed in a human neutrophil-like cell line. In
      contrast to the proatherogenic properties of fluoxetine, pharmacological
      inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1
      did not promote atherosclerosis, suggesting that the proatherogenic effect of
      fluoxetine occurs independent of peripheral 5-HT depletion. CONCLUSIONS: SSRI
      intake may promote atherosclerosis and therefore potentially increase the risk
      for acute cardiovascular events by a mechanism that is independent of 5-HT
      depletion.

PMID- 29567679
TI  - Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a)
      Concentrations in Finns.
AB  - OBJECTIVE: Lp(a) (lipoprotein(a)) concentrations are widely genetically
      determined by the LPA isoforms and show 5-fold interpopulation differences. Two-
      to 3-fold differences have been reported even within Europe. Finns represent a
      distinctive population isolate within Europe and have been repeatedly reported to
      present lower Lp(a) concentrations than Central Europeans. The significance of
      this finding was unclear for a long time because of the difficult comparability
      of Lp(a) assays. Recently, a large standardized study in >50 000 individuals from
      7 European populations confirmed this observation but could not provide insights
      into the causes. APPROACH AND RESULTS: We investigated Lp(a) concentrations, LPA
      isoforms, and genotypes of established genetic variants affecting Lp(a)
      concentrations (LPA variants, APOE isoforms, and PCSK9 R46L) in the Finnish YFS
      (Cardiovascular Risk in Young Finns Study) population (n=2281) and 3 Non-Finnish
      Central European populations (n=10 003). We observed ~50% lower Lp(a)
      concentrations in Finns. The isoform distribution was shifted toward longer
      isoforms, and the percentage of low-molecular-weight isoform carriers was
      reduced. Most interestingly, however, Lp(a) was reduced in each single-isoform
      group. In contrast to the known inverse relationship between LPA isoforms and
      Lp(a) concentrations, especially very short isoforms presented unexpectedly low
      Lp(a) concentrations in Finns. The investigated genetic variants, as well as age,
      sex, and renal function, explained 71.8% of the observed population differences.
      CONCLUSIONS: The population differences in Lp(a) concentrations between Finnish
      and Central European populations originate not only from a different LPA isoform
      distribution but suggest the existence of novel functional variation in the small
      isoform range.

PMID- 29567682
TI  - Lumping and splitting.

PMID- 29567683
TI  - News at a glance.

PMID- 29567681
TI  - Classical Pathway of Complement Activation: Longitudinal Associations of C1q and
      C1-INH With Cardiovascular Outcomes: The CODAM Study (Cohort on Diabetes and
      Atherosclerosis Maastricht)-Brief Report.
AB  - OBJECTIVE: The classical complement pathway has been assigned both protective and
      pathological effects in cardiovascular disease (CVD), but human data are lacking.
      We determined the associations of the pattern recognition factor C1q and the
      regulator C1-INH (C1-inhibitor) with incident CVD, carotid intima-media
      thickness, endothelial dysfunction, and low-grade inflammation. APPROACH AND
      RESULTS: Baseline concentrations of C1q and C1-INH were measured in the CODAM
      study (Cohort on Diabetes and Atherosclerosis Maastricht; n=574; 61% men; age,
      60+/-7 years). The 7-year incidence of CVD in participants free of CVD at
      baseline was evaluated using logistic regression analyses (n=342; 73 cases). The
      lowest incidence of CVD was observed in the middle tertile of C1q (Tlow compared
      with Tmiddle: odds ratio, 2.38 [95% confidence interval, 1.14-4.95]; Thigh
      compared with Tmiddle: odds ratio, 1.96 [95% confidence interval, 0.94-4.07]). C1
      INH was not associated with CVD. During the 7-year follow-up period, C1q and C1
      INH were not, or inconsistently, associated with carotid intima-media thickness
      or with biomarker scores reflecting endothelial dysfunction and low-grade
      inflammation. CONCLUSIONS: Our results suggest a nonlinear association between
      C1q and incident CVD. This supports the concept that early steps in classical
      pathway activation may have both protective and pathological effects on human
      CVD.

PMID- 29567685
TI  - Accounting rules hobble Spanish institutes.

PMID- 29567684
TI  - U.K. attack puts nerve agent in the spotlight.

PMID- 29567686
TI  - Hawking's bid to save quantum theory from black holes.

PMID- 29567687
TI  - Stephen Hawking, betting man.

PMID- 29567689
TI  - A research behemoth is born in Britain.

PMID- 29567688
TI  - Protein may explain morning sickness, and worse.

PMID- 29567690
TI  - The realist.

PMID- 29567691
TI  - Are wood pellets a green fuel?

PMID- 29567692
TI  - Early life experience shapes neural genome.

PMID- 29567693
TI  - RNA targeting and translation in axons.

PMID- 29567694
TI  - From rock-stable to reactive phosphorus.

PMID- 29567695
TI  - A radical advance for conducting polymers.

PMID- 29567696
TI  - Targeting angiogenic metabolism in disease.

PMID- 29567697
TI  - Expanded health systems for sustainable development.

PMID- 29567698
TI  - Shortfin mako sharks threatened by inaction.

PMID- 29567699
TI  - Mitigate risk for Malaysia's mangroves.

PMID- 29567700
TI  - India's Ph.D. scholar outreach requirement.

PMID- 29567702
TI  - The Cancer Immunotherapy Revolution.

PMID- 29567703
TI  - Too much of a good thing?

PMID- 29567704
TI  - Sticker shock.

PMID- 29567705
TI  - Cancer immunotherapy using checkpoint blockade.
AB  - The release of negative regulators of immune activation (immune checkpoints) that
      limit antitumor responses has resulted in unprecedented rates of long-lasting
      tumor responses in patients with a variety of cancers. This can be achieved by
      antibodies blocking the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) or
      the programmed cell death 1 (PD-1) pathway, either alone or in combination. The
      main premise for inducing an immune response is the preexistence of antitumor T
      cells that were limited by specific immune checkpoints. Most patients who have
      tumor responses maintain long-lasting disease control, yet one-third of patients
      relapse. Mechanisms of acquired resistance are currently poorly understood, but
      evidence points to alterations that converge on the antigen presentation and
      interferon-gamma signaling pathways. New-generation combinatorial therapies may
      overcome resistance mechanisms to immune checkpoint therapy.

PMID- 29567706
TI  - Personalized vaccines for cancer immunotherapy.
AB  - Cancer is characterized by an accumulation of genetic alterations. Somatic
      mutations can generate cancer-specific neoepitopes that are recognized by
      autologous T cells as foreign and constitute ideal cancer vaccine targets. Every
      tumor has its own unique composition of mutations, with only a small fraction
      shared between patients. Technological advances in genomics, data science, and
      cancer immunotherapy now enable the rapid mapping of the mutations within a
      genome, rational selection of vaccine targets, and on-demand production of a
      therapy customized to a patient's individual tumor. First-in-human clinical
      trials of personalized cancer vaccines have shown the feasibility, safety, and
      immunotherapeutic activity of targeting individual tumor mutation signatures.
      With vaccination development being promoted by emerging innovations of the
      digital age, vaccinating a patient with individual tumor mutations may become the
      first truly personalized treatment for cancer.

PMID- 29567707
TI  - CAR T cell immunotherapy for human cancer.
AB  - Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving
      the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory
      effects. The field has rapidly advanced from a promising form of immuno-oncology
      in preclinical models to the recent commercial approvals of chimeric antigen
      receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes
      opportunities and challenges for entering mainstream oncology that presently face
      the CAR T field, with a focus on the challenges that have emerged over the past
      several years.

PMID- 29567708
TI  - The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic
      strategies.
AB  - The fine line between human health and disease can be driven by the interplay
      between host and microbial factors. This "metagenome" regulates cancer
      initiation, progression, and response to therapies. Besides the capacity of
      distinct microbial species to modulate the pharmacodynamics of chemotherapeutic
      drugs, symbiosis between epithelial barriers and their microbial ecosystems has a
      major impact on the local and distant immune system, markedly influencing
      clinical outcome in cancer patients. Efficacy of cancer immunotherapy with immune
      checkpoint antibodies can be diminished with administration of antibiotics, and
      superior efficacy is observed with the presence of specific gut microbes. Future
      strategies of precision medicine will likely rely on novel diagnostic and
      therapeutic tools with which to identify and correct defects in the microbiome
      that compromise therapeutic efficacy.

PMID- 29567709
TI  - Bioinspired spring origami.
AB  - Origami enables folding of objects into a variety of shapes in arts, engineering,
      and biological systems. In contrast to well-known paper-folded objects, the wing
      of the earwig has an exquisite natural folding system that cannot be sufficiently
      described by current origami models. Such an unusual biological system displays
      incompatible folding patterns, remains open by a bistable locking mechanism
      during flight, and self-folds rapidly without muscular actuation. We show that
      these notable functionalities arise from the protein-rich joints of the earwig
      wing, which work as extensional and rotational springs between facets. Inspired
      by this biological wing, we establish a spring origami model that broadens the
      folding design space of traditional origami and allows for the fabrication of
      precisely tunable, four-dimensional-printed objects with programmable bioinspired
      morphing functionalities.

PMID- 29567710
TI  - A nonconjugated radical polymer glass with high electrical conductivity.
AB  - Solid-state conducting polymers usually have highly conjugated macromolecular
      backbones and require intentional doping in order to achieve high electrical
      conductivities. Conversely, single-component, charge-neutral macromolecules could
      be synthetically simpler and have improved processibility and ambient stability.
      We show that poly(4-glycidyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a
      nonconjugated radical polymer with a subambient glass transition temperature,
      underwent rapid solid-state charge transfer reactions and had an electrical
      conductivity of up to 28 siemens per meter over channel lengths up to 0.6
      micrometers. The charge transport through the radical polymer film was enabled
      with thermal annealing at 80 degrees C, which allowed for the formation of a
      percolating network of open-shell sites in electronic communication with one
      another. The electrical conductivity was not enhanced by intentional doping, and
      thin films of this material showed high optical transparency.

PMID- 29567711
TI  - Early life experience drives structural variation of neural genomes in mice.
AB  - The brain is a genomic mosaic owing to somatic mutations that arise throughout
      development. Mobile genetic elements, including retrotransposons, are one source
      of somatic mosaicism in the brain. Retrotransposition may represent a form of
      plasticity in response to experience. Here, we use droplet digital polymerase
      chain reaction to show that natural variations in maternal care mediate the
      mobilization of long interspersed nuclear element-1 (LINE-1 or L1)
      retrotransposons in the hippocampus of the mouse brain. Increasing the amount of
      maternal care blocks the accumulation of L1. Maternal care also alters DNA
      methylation at YY1 binding sites implicated in L1 activation and affects
      expression of the de novo methyltransferase DNMT3a. Our observations indicate
      that early life experience drives somatic variation in the genome via L1
      retrotransposons.

PMID- 29567712
TI  - A single fungal MAP kinase controls plant cell-to-cell invasion by the rice blast
      fungus.
AB  - Blast disease destroys up to 30% of the rice crop annually and threatens global
      food security. The blast fungus Magnaporthe oryzae invades plant tissue with
      hyphae that proliferate and grow from cell to cell, often through pit fields,
      where plasmodesmata cluster. We showed that chemical genetic inhibition of a
      single fungal mitogen-activated protein (MAP) kinase, Pmk1, prevents M. oryzae
      from infecting adjacent plant cells, leaving the fungus trapped within a single
      plant cell. Pmk1 regulates expression of secreted fungal effector proteins
      implicated in suppression of host immune defenses, preventing reactive oxygen
      species generation and excessive callose deposition at plasmodesmata.
      Furthermore, Pmk1 controls the hyphal constriction required for fungal growth
      from one rice cell to the neighboring cell, enabling host tissue colonization and
      blast disease.

PMID- 29567714
TI  - Lymph node blood vessels provide exit routes for metastatic tumor cell
      dissemination in mice.
AB  - During metastasis, malignant cells escape the primary tumor, intravasate
      lymphatic vessels, and reach draining sentinel lymph nodes before they colonize
      distant organs via the blood circulation. Although lymph node metastasis in
      cancer patients correlates with poor prognosis, evidence is lacking as to whether
      and how tumor cells enter the bloodstream via lymph nodes. To investigate this
      question, we delivered carcinoma cells into the lymph nodes of mice by
      microinfusing the cells into afferent lymphatic vessels. We found that tumor
      cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and
      seeded lung metastases without involvement of the thoracic duct. These results
      suggest that the lymph node blood vessels can serve as an exit route for systemic
      dissemination of cancer cells in experimental mouse models. Whether this form of
      tumor cell spreading occurs in cancer patients remains to be determined.

PMID- 29567713
TI  - Lymph node metastases can invade local blood vessels, exit the node, and colonize
      distant organs in mice.
AB  - Lymph node metastases in cancer patients are associated with tumor
      aggressiveness, poorer prognoses, and the recommendation for systemic therapy.
      Whether cancer cells in lymph nodes can seed distant metastases has been a
      subject of considerable debate. We studied mice implanted with cancer cells
      (mammary carcinoma, squamous cell carcinoma, or melanoma) expressing the
      photoconvertible protein Dendra2. This technology allowed us to selectively
      photoconvert metastatic cells in the lymph node and trace their fate. We found
      that a fraction of these cells invaded lymph node blood vessels, entered the
      blood circulation, and colonized the lung. Thus, in mouse models, lymph node
      metastases can be a source of cancer cells for distant metastases. Whether this
      mode of dissemination occurs in cancer patients remains to be determined.

PMID- 29567715
TI  - The biosynthesis of methanobactin.
AB  - Metal homeostasis poses a major challenge to microbes, which must acquire scarce
      elements for core metabolic processes. Methanobactin, an extensively modified
      copper-chelating peptide, was one of the earliest natural products shown to
      enable microbial acquisition of a metal other than iron. We describe the core
      biosynthetic machinery responsible for the characteristic posttranslational
      modifications that grant methanobactin its specificity and affinity for copper. A
      heterodimer comprising MbnB, a DUF692 family iron enzyme, and MbnC, a protein
      from a previously unknown family, performs a dioxygen-dependent four-electron
      oxidation of the precursor peptide (MbnA) to install an oxazolone and an adjacent
      thioamide, the characteristic methanobactin bidentate copper ligands. MbnB and
      MbnC homologs are encoded together and separately in many bacterial genomes,
      suggesting functions beyond their roles in methanobactin biosynthesis.

PMID- 29567716
TI  - Locally translated mTOR controls axonal local translation in nerve injury.
AB  - How is protein synthesis initiated locally in neurons? We found that mTOR
      (mechanistic target of rapamycin) was activated and then up-regulated in injured
      axons, owing to local translation of mTOR messenger RNA (mRNA). This mRNA was
      transported into axons by the cell size-regulating RNA-binding protein nucleolin.
      Furthermore, mTOR controlled local translation in injured axons. This included
      regulation of its own translation and that of retrograde injury signaling
      molecules such as importin beta1 and STAT3 (signal transducer and activator of
      transcription 3). Deletion of the mTOR 3' untranslated region (3'UTR) in mice
      reduced mTOR in axons and decreased local translation after nerve injury. Both
      pharmacological inhibition of mTOR in axons and deletion of the mTOR 3'UTR
      decreased proprioceptive neuronal survival after nerve injury. Thus, mRNA
      localization enables spatiotemporal control of mTOR pathways regulating local
      translation and long-range intracellular signaling.

PMID- 29567718
TI  - ERJ March Podcast: World TB Day.

PMID- 29567717
TI  - The freedom of choice.

PMID- 29567719
TI  - The World Health Organization global aDSM database: generating evidence on the
      safety of new treatment regimens for drug-resistant tuberculosis.

PMID- 29567720
TI  - Renal Fanconi syndrome with meropenem-containing regimen in drug-resistant
      tuberculosis.

PMID- 29567721
TI  - Eligibility for the shorter regimen for multidrug-resistant tuberculosis in
      Mexico.

PMID- 29567722
TI  - Will regulatory issues continue to be a major barrier to access to bedaquiline
      and delamanid?

PMID- 29567723
TI  - Closing the gap in surveillance of tuberculosis and HIV co-infection, and the
      need for clinician-public health alliances.

PMID- 29567724
TI  - The World Health Organization standards for tuberculosis care and management.

PMID- 29567725
TI  - T-cell biomarkers for diagnosis of tuberculosis: candidate evaluation by a simple
      whole blood assay for clinical translation.

PMID- 29567727
TI  - Uptake of governmental social protection and financial hardship during drug
      resistant tuberculosis treatment in Rio de Janeiro, Brazil.

PMID- 29567726
TI  - Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease:
      an NTM-NET consensus statement.

PMID- 29567728
TI  - Pragmatic tuberculosis prevention policies for primary care in low- and middle
      income countries.

PMID- 29567729
TI  - Call for new impetus to tackle TB across Europe.

PMID- 29567730
TI  - A Proposed New Strain of Avian Picornavirus in Broiler Chicken from Brazil.
AB  - A new strain of avian picornavirus was identified in fecal samples from broiler
      chickens in a commercial farm in the municipality of Benevides, Para, Brazil.
      Genomic analysis showed it to have a nucleotide identity of 78.4% with the family
      Picornaviridae, genus Avisivirus, and species Avisivirus A, suggesting that this
      is a possible new strain within this species.

PMID- 29567731
TI  - Draft Genome Sequences of 12 Dry-Heat-Resistant Bacillus Strains Isolated from
      the Cleanrooms Where the Viking Spacecraft Were Assembled.
AB  - Spore-forming microorganisms are of concern for forward contamination because
      they can survive harsh interplanetary travel. Here, we report the draft genome
      sequences of 12 spore-forming strains isolated from the Manned Spacecraft
      Operations Building (MSOB) and the Vehicle Assembly Building (VAB) in Cape
      Canaveral, FL, where the Viking spacecraft were assembled.

PMID- 29567732
TI  - Genome Sequences of 15 Klebsiella sp. Isolates from Sugarcane Fields in
      Colombia's Cauca Valley.
AB  - Members of the Klebsiella genus promote plant growth. We report here draft whole
      genome sequences for 15 Klebsiella sp. isolates from sugarcane fields in the
      Cauca Valley of Colombia. The genomes of these isolates were characterized as
      part of a broader effort to evaluate their utility as endemic plant growth
      promoting biofertilizers.

PMID- 29567733
TI  - Draft Genome Sequences of Endophytic Isolates of Klebsiella variicola and
      Klebsiella pneumoniae Obtained from the Same Sugarcane Plant.
AB  - Endophytic Klebsiella variicola KvMx2 and Klebsiella pneumoniae KpMx1 isolates
      obtained from the same sugarcane stem were used for whole-genome sequencing. The
      genomes revealed clear differences in essential genes for plant growth,
      development, and detoxification, as well as nitrogen fixation, catalases,
      cellulases, and shared virulence factors described in the K. pneumoniae pathogen.

PMID- 29567734
TI  - Complete Genome Sequence of Human Coronavirus NL63 CN0601/14, First Isolated in
      South Korea.
AB  - We report here the complete genome sequence of the human coronavirus NL63
      CN0601/14 strain, first isolated from South Korea. It contains 18-nucleotide
      discontinuous deletions of the open reading frame 1a (ORF1a) and spike regions.
      This study will aid in our understanding of the complete genome sequences of
      isolated coronaviruses in South Korea.

PMID- 29567735
TI  - Complete and Assembled Genome Sequence of Salmonella enterica subsp. enterica
      Serotype Senftenberg N17-509, a Strain Lacking Salmonella Pathogen Island 1.
AB  - The genome of Salmonella enterica subsp. enterica serotype Senftenberg N17-509, a
      strain isolated from desiccated coconut, was sequenced using single-molecule real
      time sequencing. It consists of a 5.1-Mbp chromosome and a 29-kb linear plasmid.

PMID- 29567736
TI  - Complete and Assembled Genome Sequences of Pantoea calida DSM 22759T and Pantoea
      gaviniae DSM 22758T.
AB  - The genomes of Pantoea calida DSM 22759T and Pantoea gaviniae DSM 22758T were
      sequenced using single-molecule real-time sequencing. They consist of a 4.3-Mbp
      chromosome containing 4,092 genes, of which 3,977 encode proteins, and a 4.5-Mbp
      chromosome containing 4,236 genes, of which 4,120 encode proteins, respectively.

PMID- 29567737
TI  - Draft Genome Sequence of Bacillus velezensis Lzh-a42, a Plant Growth-Promoting
      Rhizobacterium Isolated from Tomato Rhizosphere.
AB  - The plant growth-promoting rhizobacterium Bacillus velezensis strain Lzh-a42,
      which has antimicrobial activity, was isolated from tomato rhizosphere. Here, we
      report its genome sequence, which includes several predicted functional genes
      related to secondary metabolite biosynthesis, antimicrobial activity, and biofilm
      synthesis.

PMID- 29567738
TI  - First Complete Genome Sequences of Human Sapovirus Strains Classified as GI.3,
      GI.4, GI.6, GI.7, and GII.7.
AB  - We report here the first complete genome sequences of genotype GI.3, GI.4, GI.6,
      GI.7, and GII.7 sapovirus strains, detected from fecal samples of acute
      gastroenteritis patients. Complete or nearly complete genome sequences of all 18
      genotypes of human sapoviruses are now available for phylogenetic analysis and
      primer design.

PMID- 29567739
TI  - Complete Genomic Sequences of H3N8 Equine Influenza Virus Strains Used as Vaccine
      Strains in Japan.
AB  - We sequenced the eight segments of influenza A virus strains
      A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the
      Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus.
      These strains have been used as vaccine strains in Japan since 2016 in accordance
      with World Organization for Animal Health (OIE) recommendations.

PMID- 29567740
TI  - Complete Genome Sequence of the Live Attenuated Vaccine Strain Brucella
      melitensis Rev.1.
AB  - Live attenuated vaccines are essential elements in control programs for the
      prevention of brucellosis. Here, we report the whole-genome sequence of the
      original Elberg Brucella melitensis Rev.1 vaccine strain, passage 101 (1970).
      Commercial lines of the original strain have been successfully used in small
      ruminants worldwide.

PMID- 29567741
TI  - Next-Generation Sequencing of Haematococcus lacustris Reveals an Extremely Large
      1.35-Megabase Chloroplast Genome.
AB  - Haematococcus lacustris is an industrially relevant microalga that is used for
      the production of the carotenoid astaxanthin. Here, we report the use of PacBio
      long-read sequencing to assemble the chloroplast genome of H. lacustris strain
      UTEX:2505. At 1.35 Mb, this is the largest assembled chloroplast of any plant or
      alga known to date.

PMID- 29567742
TI  - Draft Genome Sequence of Bacillus velezensis B6, a Rhizobacterium That Can
      Control Plant Diseases.
AB  - The draft genome of Bacillus velezensis strain B6, a rhizobacterium with good
      biocontrol performance isolated from soil in China, was sequenced. The assembly
      comprises 32 scaffolds with a total size of 3.88 Mb. Gene clusters coding either
      ribosomally encoded bacteriocins or nonribosomally encoded antimicrobial
      polyketides and lipopeptides in the genome may contribute to plant disease
      control.

PMID- 29567743
TI  - Draft Genome Sequence of Carbapenem-Resistant Pseudomonas fluorescens Strain
      BWKM6, Isolated from Feces of Mareca penelope.
AB  - Migratory birds are potential vehicles of antibiotic-resistant bacteria. Here, we
      isolated the multidrug-resistant Pseudomonas fluorescens strain BWKM6 from the
      feces of Mareca penelope The strain's draft genome sequence indicates that it
      harbors a metallo-beta-lactamase, a class C beta-lactamase, and several multidrug
      efflux pumps.

PMID- 29567744
TI  - Draft Genome Sequence of Multidrug-Resistant Stenotrophomonas pavanii BWK1,
      Isolated from Mareca penelope Feces.
AB  - Migratory birds serve as vectors by transmitting antibiotic-resistant bacteria
      across large distances. Here, we isolated a multidrug-resistant Stenotrophomonas
      pavanii strain, BWK1, from Mareca penelope feces. Analysis of the draft genome
      sequence of the isolated strain indicated that BWK1 harbors a class A beta
      lactamase, metallo-beta-lactamase, and several multidrug efflux pumps.

PMID- 29567745
TI  - Complete Genome Sequences of a Hantavirus Isolate from New York.
AB  - We report here the complete genome sequences for all three segments of the New
      York hantavirus (New York 1). This is the first reported L segment sequence for
      hantaviruses maintained in Peromyscus spp. endemic to the eastern United States
      and Canada.

PMID- 29567746
TI  - Near-Complete Genome Sequence of a Novel Single-Stranded RNA Virus Discovered in
      Indoor Air.
AB  - Viral metagenomic analysis of heating, ventilation, and air conditioning (HVAC)
      filters recovered the near-complete genome sequence of a novel virus, named HVAC
      associated RNA virus 1 (HVAC-RV1). The HVAC-RV1 genome is most similar to those
      of picorna-like viruses identified in arthropods but encodes a small domain
      observed only in negative-sense single-stranded RNA viruses.

PMID- 29567747
TI  - Complete Genome Sequence of Altererythrobacter sp. Strain B11, an Aromatic
      Monomer-Degrading Bacterium, Isolated from Deep-Sea Sediment under the Seabed off
      Kashima, Japan.
AB  - Altererythrobacter sp. strain B11 is an aromatic monomer-degrading bacterium
      newly isolated from sediment under the seabed off Kashima, Japan, at a depth of
      2,100 m. Here, we report the complete nucleotide sequence of the genome of strain
      B11.

PMID- 29567749
TI  - What sort of person could have a radically extended lifespan?

PMID- 29567748
TI  - Complete Genome Sequence of Loktanella vestfoldensis Strain SMR4r, a Novel Strain
      Isolated from a Culture of the Chain-Forming Diatom Skeletonema marinoi.
AB  - We report here the genome sequence of Loktanella vestfoldensis strain SMR4r,
      isolated from the marine diatom Skeletonema marinoi strain RO5AC. Its 3,987,360
      bp genome consists of a circular chromosome and two circular plasmids, one of
      which appears to be shared with an S. marinoi-associated Roseovarius species.

PMID- 29567750
TI  - Ethics briefing.

PMID- 29567751
TI  - Selective tumour necrosis factor receptor-1 inhibition in acute lung injury: a
      new hope or a false dawn?

PMID- 29567752
TI  - Consensus on MRD in AML?

PMID- 29567753
TI  - Woody eyes, be gone!

PMID- 29567754
TI  - Set(d1a)-ing novel links between HSC regulators.

PMID- 29567755
TI  - There is nothing minimal about residual disease.

PMID- 29567756
TI  - Treating hemophilia by targeting protein S?

PMID- 29567757
TI  - HSCT for GATA2 deficiency across the pond.

PMID- 29567758
TI  - Severe acute anemia attributable to concomitant occurrence of AIHA with PRCA
      induced by parvovirus B19 infection.

PMID- 29567759
TI  - Differential diagnosis of myelodysplastic syndrome: anemia associated with copper
      deficiency.

PMID- 29567760
TI  - Blatt K, Cerny-Reiterer S, Schwaab J, et al. Identification of the Ki-1 antigen
      (CD30) as a novel therapeutic target in systemic mastocytosis. Blood.
      2015;126(26):2832-2841.

PMID- 29567761
TI  - SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke):
      A Randomized Controlled Phase 2 Trial.
AB  - BACKGROUND AND PURPOSE: The proinflammatory cytokine IL-1 (interleukin-1) has a
      deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor
      antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as
      interleukin-6, which are associated with worse prognosis after ischemic stroke.
      We investigated whether subcutaneous IL-1Ra reduces the peripheral inflammatory
      response in acute ischemic stroke. METHODS: SCIL-STROKE (Subcutaneous Interleukin
      1 Receptor Antagonist in Ischemic Stroke) was a single-center, double-blind,
      randomized, placebo-controlled phase 2 trial of subcutaneous IL-1Ra (100 mg
      administered twice daily for 3 days) in patients presenting within 5 hours of
      ischemic stroke onset. Randomization was stratified for baseline National
      Institutes of Health Stroke Scale score and thrombolysis. Measurement of plasma
      interleukin-6 and other peripheral inflammatory markers was undertaken at 5 time
      points. The primary outcome was difference in concentration of log(interleukin-6)
      as area under the curve to day 3. Secondary outcomes included exploratory effect
      of IL-1Ra on 3-month outcome with the modified Rankin Scale. RESULTS: We
      recruited 80 patients (mean age, 72 years; median National Institutes of Health
      Stroke Scale, 12) of whom 73% received intravenous thrombolysis with alteplase.
      IL-1Ra significantly reduced plasma interleukin-6 (P<0.001) and plasma C-reactive
      protein (P<0.001). IL-1Ra was well tolerated with no safety concerns. Allocation
      to IL-1Ra was not associated with a favorable outcome on modified Rankin Scale:
      odds ratio (95% confidence interval)=0.67 (0.29-1.52), P=0.34. Exploratory
      mediation analysis suggested that IL-1Ra improved clinical outcome by reducing
      inflammation, but there was a statistically significant, alternative mechanism
      countering this benefit. CONCLUSIONS: IL-1Ra reduced plasma inflammatory markers
      which are known to be associated with worse clinical outcome in ischemic stroke.
      Subcutaneous IL-1Ra is safe and well tolerated. Further experimental studies are
      required to investigate efficacy and possible interactions of IL-1Ra with
      thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: ISRCTN74236229.

PMID- 29567762
TI  - Improving Community Stroke Preparedness in the HHS (Hip-Hop Stroke) Randomized
      Clinical Trial.
AB  - BACKGROUND AND PURPOSE: Deficiencies in stroke preparedness cause major delays to
      stroke thrombolysis, particularly among economically disadvantaged minorities. We
      evaluated the effectiveness of a stroke preparedness intervention delivered to
      preadolescent urban public school children on the stroke knowledge/preparedness
      of their parents. METHODS: We recruited 3070 fourth through sixth graders and
      1144 parents from 22 schools into a cluster randomized trial with schools
      randomized to the HHS (Hip-Hop Stroke) intervention or attentional control
      (nutrition classes). HHS is a 3-hour culturally tailored, theory-based,
      multimedia stroke literacy intervention targeting school children, which
      systematically empowers children to share stroke information with parents. Our
      main outcome measures were stroke knowledge/preparedness of children and parents
      using validated surrogates. RESULTS: Among children, it was estimated that 1%
      (95% confidence interval [CI], 0%-1%) of controls and 2% (95% CI, 1%-4%; P=0.09)
      of the intervention group demonstrated optimal stroke preparedness (perfect
      scores on the knowledge/preparedness test) at baseline, increasing to 57% (95%
      CI, 44%-69%) immediately after the program in the intervention group compared
      with 1% (95% CI, 0%-1%; P<0.001) among controls. At 3-month follow-up, 24% (95%
      CI, 15%-33%) of the intervention group retained optimal preparedness, compared
      with 2% (95% CI, 0%-3%; P<0.001) of controls. Only 3% (95% CI, 2%-4%) of parents
      in the intervention group could identify all 4 letters of the stroke FAST (Facial
      droop, Arm weakness, Speech disturbance, Time to call 911) acronym at baseline,
      increasing to 20% at immediate post-test (95% CI, 16%-24%) and 17% at 3-month
      delayed post-test (95% CI, 13%-21%; P=0.0062), with no significant changes (3%
      identification) among controls. Four children, all in the intervention group,
      called 911 for real-life stroke symptoms, in 1 case overruling a parent's wait
      and-see approach. CONCLUSIONS: HHS is an effective, intergenerational model for
      increasing stroke preparedness among economically disadvantaged minorities.
      CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:
      NCT01497886.

PMID- 29567763
TI  - Long-Term Morphological Changes of Symptomatic Lacunar Infarcts and Surrounding
      White Matter on Structural Magnetic Resonance Imaging.
AB  - BACKGROUND AND PURPOSE: Insights into evolution of cerebral small vessel disease
      on neuroimaging might advance knowledge of the natural disease course. Data on
      evolution of sporadic symptomatic lacunar infarcts are limited. We investigated
      long-term changes of symptomatic lacunar infarcts and surrounding white matter on
      structural magnetic resonance imaging. METHODS: From 2 nonoverlapping, single
      center, prospective observational stroke studies, we selected patients presenting
      with lacunar stroke symptoms with a recent small subcortical (lacunar) infarct on
      baseline structural magnetic resonance imaging and with follow-up magnetic
      resonance imaging available at 1 to 5 years. We assessed changes in imaging
      characteristics of symptomatic lacunar infarcts and surrounding white matter.
      RESULTS: We included 79 patients of whom 32 (41%) had complete and 40 (51%) had
      partial cavitation of the index lesion at median follow-up of 403 (range, 315
      1781) days. In 42 of 79 (53%) patients, we observed a new white matter
      hyperintensity adjacent to the index infarct, either superior (white matter
      hyperintensity cap, n=17), inferior (white matter hyperintensity track, n=13), or
      both (n=12). CONCLUSIONS: Half of the sporadic symptomatic lacunar infarcts
      developed secondary changes in superior and inferior white matter. These white
      matter hyperintensity caps and tracks may reflect another aspect of cerebral
      small vessel-related disease progression. The clinical and prognostic values
      remain to be determined.

PMID- 29567764
TI  - Moderate-to-Vigorous Physical Activity and All-Cause Mortality: Do Bouts Matter?
AB  - BACKGROUND: The 2008 Physical Activity Guidelines for Americans recommends that
      adults accumulate moderate-to-vigorous physical activity (MVPA) in bouts of >=10
      minutes for substantial health benefits. To what extent the same amount of MVPA
      accumulated in bouts versus sporadically reduces mortality risk remains unclear.
      METHODS AND RESULTS: We analyzed data from the National Health and Nutrition
      Examination Survey 2003-2006 and death records available through 2011 (follow-up
      period of ~6.6 years; 700 deaths) to examine the associations between objectively
      measured physical activity accumulated with and without a bout criteria and all
      cause mortality in a representative sample of US adults 40 years and older
      (n=4840). Physical activity data were processed to generate minutes per day of
      total and bouted MVPA. Bouted MVPA was defined as MVPA accumulated in bouts of a
      minimum duration of either 5 or 10 minutes allowing for 1- to 2-minute
      interruptions. Hazard ratios for all-cause mortality associated with total and
      bouted MVPA were similar and ranged from 0.24 for the third quartile of total to
      0.44 for the second quartile of 10-minute bouts. The examination of jointly
      classified quartiles of total MVPA and tertiles of proportion of bouted activity
      revealed that greater amounts of bouted MVPA did not result in additional risk
      reductions for mortality. CONCLUSIONS: These results provide evidence that
      mortality risk reductions associated with MVPA are independent of how activity is
      accumulated and can impact the development of physical activity guidelines and
      inform clinical practice.

PMID- 29567765
TI  - Accumulation of Moderate-to-Vigorous Physical Activity and All-Cause Mortality.

PMID- 29567767
TI  - Knee pain after a fall.

PMID- 29567766
TI  - Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug
      resistant phenotype.
AB  - In BRAFV600E melanoma cells, a global metabolomic analysis discloses a decrease
      in nicotinamide adenine dinucleotide (NAD+) levels upon PLX4032 treatment that is
      conveyed by a STAT5 inhibition and a transcriptional regulation of the
      nicotinamide phosphoribosyltransferase (NAMPT) gene. NAMPT inhibition decreases
      melanoma cell proliferation both in vitro and in vivo, while forced NAMPT
      expression renders melanoma cells resistant to PLX4032. NAMPT expression induces
      transcriptomic and epigenetic reshufflings that steer melanoma cells toward an
      invasive phenotype associated with resistance to targeted therapies and
      immunotherapies. Therefore, NAMPT, the key enzyme in the NAD+ salvage pathway,
      appears as a rational target in targeted therapy-resistant melanoma cells and a
      key player in phenotypic plasticity of melanoma cells.

PMID- 29567769
TI  - Automated decision tree to evaluate genetic abnormalities when determining
      prognostic risk in acute myeloid leukemia.

PMID- 29567768
TI  - Highly sensitive MYD88L265P mutation detection by droplet digital polymerase
      chain reaction in Waldenstrom macroglobulinemia.
AB  - We here describe a novel method for MYD88L265P mutation detection and minimal
      residual disease monitoring in Waldenstrom macroglobulinemia, by droplet digital
      polymerase chain reaction, in bone marrow and peripheral blood cells, as well as
      in circulating cell-free DNA. Our method shows a sensitivity of 5.00*10-5, which
      is far superior to the widely used allele-specific polymerase chain reaction
      (1.00*10-3). Overall, 291 unsorted samples from 148 patients (133 with
      Waldenstrom macroglobulinemia, 11 with IgG lymphoplasmacytic lymphoma and 4 with
      IgM monoclonal gammopathy of undetermined significance) were analyzed: 194 were
      baseline samples and 97 were followup samples. One hundred and twenty-two of 128
      (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored
      positive for MYD88L265P To investigate whether MYD88L265P detection by droplet
      digital polymerase chain reaction could be used for minimal residual disease
      monitoring, mutation levels were compared with IGH-based minimal residual disease
      analysis in 10 patients, and was found to be as informative as the classical,
      standardized, but not yet validated in Waldenstrom macroglobulinemia, IGH-based
      minimal residual disease assay (r2=0.64). Finally, MYD88L265P detection by
      droplet digital polymerase chain reaction on plasma circulating tumor DNA from 60
      patients showed a good correlation with bone marrow findings (bone marrow median
      mutational value 1.92*10-2, plasma circulating tumor DNA value: 1.4*10-2,
      peripheral blood value: 1.03*10-3). This study indicates that droplet digital
      polymerase chain reaction assay of MYD88L265P is a feasible and sensitive tool
      for mutation screening and minimal residual disease monitoring in Waldenstrom
      macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be
      reliably tested, as can circulating tumor DNA, which represents an attractive,
      less invasive alternative to bone marrow for MYD88L265P detection.

PMID- 29567771
TI  - Gene expression profiling reveals a close relationship between follicular
      lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1
      and 2.
AB  - A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has
      been favored, since FL3A often co-exist with an FL1/2 component. FL3B, in
      contrast, is thought to be more closely related to diffuse large B-cell lymphoma
      (DLBCL), and both are often simultaneously present in one tumor (DLBCL/FL3B). To
      obtain more detailed insights into follicular lymphoma progression, a
      comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B
      (n=6), DLBCL/FL3B (n=9), and germinal center B-cell-type diffuse large B-cell
      lymphoma (n=45) was undertaken using gene expression profiling,
      immunohistochemical stainings and genetic analyses by fluorescence in situ
      hybridization. While immunohistochemical (CD10, IRF4/MUM1, Ki67, BCL2, BCL6) and
      genetic profiles (translocations of BCL2, BCL6 and MYC) delineate FL1-3A from
      FL3B and DLBCL/FL3B, significant differences were observed between FL1/2 and FL3A
      upon gene expression profiling. Interestingly, FL3B turned out to be closely
      related to FL3A, not categorizing within a separate gene expression cluster, and
      both FL3A and FL3B showed overlapping profiles in between FL1/2 and diffuse large
      B-cell lymphoma. Finally, based upon their gene expression pattern, DLBCL/FL3B
      represent a composite form of FL3B and DLBCL, with the majority of samples more
      closely resembling the latter. The fact that gene expression profiling clearly
      separated FL1/2 from both FL3A and FL3B suggests a closer biological relationship
      between the latter. This notion, however, is in contrast to immunohistochemical
      and genetic profiles of the different histological FL subtypes that point to a
      closer relationship between FL1/2 and FL3A, and separates them from FL3B.

PMID- 29567770
TI  - Fit alphabeta T-cell receptor suppresses leukemogenesis of Pten-deficient
      thymocytes.
AB  - Signaling through the alphabetaT cell receptor (TCR) is a crucial determinant of
      T-cell fate and can induce two opposite outcomes during thymocyte development:
      cell death or survival and differentiation. To date, the role played by T-cell
      receptor in the oncogenic transformation of developing T cells remains unclear.
      Here we show that human primary T-cell acute lymphoblastic leukemias expressing
      an alphabetaT cell receptor are frequently deficient for phosphatase and tensin
      homolog protein (PTEN), and fail to respond strongly to T-cell receptor
      activation. Using Pten-deficient T-cell acute lymphoblastic leukemia mouse
      models, we confirm that T-cell receptor signaling is involved in leukemogenesis.
      We show that abrogation of T-cell receptor expression accelerated tumor onset,
      while enforced expression of a fit transgenic T-cell receptor led to the
      development of T-cell receptor-negative lymphoma and delayed tumorigenesis. We
      further demonstrate that pre-tumoral Pten-deficient thymocytes harboring fit T
      cell receptors undergo early clonal deletion, thus preventing their malignant
      transformation, while cells with unfit T-cell receptors that should normally be
      deleted during positive selection, pass selection and develop T-cell acute
      lymphoblastic leukemias. Altogether, our data show that fit T-cell receptor
      signaling suppresses tumor development mediated by Pten loss-of-function and
      point towards a role of Pten in positive selection.

PMID- 29567772
TI  - Molecular genetic characterization of myeloid/lymphoid neoplasms associated with
      eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2.

PMID- 29567773
TI  - JAK2V617F-bearing vascular niche enhances malignant hematopoietic regeneration
      following radiation injury.
AB  - Myeloproliferative neoplasms are clonal stem cell disorders characterized by
      hematopoietic stem/progenitor cell expansion. The acquired kinase mutation
      JAK2V617F plays a central role in these disorders. Abnormalities of the marrow
      microenvironment are beginning to be recognized as an important factor in the
      development of myeloproliferative neoplasms. Endothelial cells are an essential
      component of the hematopoietic vascular niche. Endothelial cells carrying the
      JAK2V617F mutation can be detected in patients with myeloproliferative neoplasms,
      suggesting that the mutant vascular niche is involved in the pathogenesis of
      these disorders. Here, using a transgenic mouse expressing JAK2V617F specifically
      in all hematopoietic cells (including hematopoietic stem/progenitor cells) and
      endothelial cells, we show that the JAK2V617F-mutant hematopoietic
      stem/progenitor cells are relatively protected by the JAK2V617F-bearing vascular
      niche from an otherwise lethal dose of irradiation during conditioning for stem
      cell transplantation. Gene expression analysis revealed that chemokine (C-X-C
      motif) ligand 12, epidermal growth factor, and pleiotrophin are up-regulated in
      irradiated JAK2V617F-bearing endothelial cells compared to wild-type cells. Our
      findings suggest that the mutant vascular niche may contribute to the high
      incidence of disease relapse in patients with myeloproliferative neoplasms
      following allogeneic stem cell transplantation, the only curative treatment for
      these disorders.

PMID- 29567774
TI  - Lenalidomide results in a durable complete remission in acute myeloid leukemia
      accompanied by persistence of somatic mutations and a T-cell infiltrate in the
      bone marrow.

PMID- 29567775
TI  - Low-count monoclonal B-cell lymphocytosis persists after seven years of follow up
      and is associated with a poorer outcome.
AB  - Low-count monoclonal B-cell lymphocytosis is defined by the presence of very low
      numbers of circulating clonal B cells, usually phenotypically similar to chronic
      lymphocytic leukemia cells, whose biological and clinical significance remains
      elusive. Herein, we re-evaluated 65/91 low-count monoclonal B-cell lymphocytosis
      cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic
      leukemia-like) followed-up for a median of seven years, using high-sensitivity
      flow cytometry and interphase fluorescence in situ hybridization. Overall, the
      clone size significantly increased in 69% of low-count monoclonal B-cell
      lymphocytosis cases, but only one subject progressed to high-count monoclonal B
      cell lymphocytosis. In parallel, the frequency of cytogenetic alterations
      increased over time (32% vs 61% of cases, respectively). The absolute number of
      the major T-cell and natural killer cell populations also increased, but only
      among chronic lymphocytic leukemia-like cases with increased clone size vs age-
      and sex-matched controls. Although progression to chronic lymphocytic leukemia
      was not observed, the overall survival of low-count monoclonal B-cell
      lymphocytosis individuals was significantly reduced vs non-monoclonal B-cell
      lymphocytosis controls (P=0.03) plus the general population from the same region
      (P<=0.001), particularly among females (P=0.01); infection and cancer were the
      main causes of death in low-count monoclonal B-cell lymphocytosis. In summary,
      despite the fact that mid-term progression from low-count monoclonal B-cell
      lymphocytosis to high-count monoclonal B-cell lymphocytosis and chronic
      lymphocytic leukemia appears to be unlikely, these clones persist at increased
      numbers, usually carrying more genetic alterations, and might thus be a marker of
      an impaired immune system indirectly associated with a poorer outcome,
      particularly among females.

PMID- 29567776
TI  - Dramatically improved survival in multiple myeloma patients in the recent decade:
      results from a Swedish population-based study.

PMID- 29567777
TI  - MK2 is a therapeutic target for high-risk multiple myeloma.

PMID- 29567778
TI  - BET-inhibition by JQ1 promotes proliferation and self-renewal capacity of
      hematopoietic stem cells.
AB  - Although inhibitors of bromodomain and extra terminal domain (BET) proteins show
      promising clinical activity in different hematologic malignancies, a systematic
      analysis of the consequences of pharmacological BET inhibition on healthy
      hematopoietic (stem) cells is urgently needed. We found that JQ1 treatment
      decreases the numbers of pre-, immature and mature B cells while numbers of early
      pro-B cells remain constant. In addition, JQ1 treatment increases apoptosis in T
      cells, all together leading to reduced cellularity in thymus, bone marrow and
      spleen. Furthermore, JQ1 induces proliferation of long-term hematopoietic stem
      cells, thereby increasing stem cell numbers. Due to increased numbers, JQ1
      treated hematopoietic stem cells engrafted better after stem cell transplantation
      and repopulated the hematopoietic system significantly faster after sublethal
      myeloablation. As quantity and functionality of hematopoietic stem cells
      determine the duration of life-threatening myelosuppression, BET inhibition might
      benefit patients in myelosuppressive conditions.

PMID- 29567780
TI  - GATA1s exerts developmental stage-specific effects in human hematopoiesis.

PMID- 29567779
TI  - Mass spectrometry-assisted identification of ADAMTS13-derived peptides presented
      on HLA-DR and HLA-DQ.
AB  - Formation of microthrombi is a hallmark of acquired thrombotic thrombocytopenic
      purpura. These microthrombi originate from insufficient processing of ultra large
      von Willebrand factor multimers by ADAMTS13 due to the development of anti
      ADAMTS13 autoantibodies. Several studies have identified the major
      histocompatibility complex class II alleles HLA-DRB1*11, HLA-DQB1*03 and HLA
      DQB1*02:02 as risk factors for acquired thrombotic thrombocytopenic purpura
      development. Previous research in our department indicated that ADAMTS13 CUB2
      domain-derived peptides FINVAPHAR and LIRDTHSLR are presented on HLA-DRB1*11 and
      HLA-DRB1*03, respectively. Here, we describe the repertoire of ADAMTS13 peptides
      presented on HLA-DQ. In parallel, the repertoire of ADAMTS13-derived peptides
      presented on HLA-DR was monitored. Using HLA-DR- and HLA-DQ-specific antibodies,
      we purified HLA/peptide complexes from ADAMTS13-pulsed monocyte-derived dendritic
      cells. Using this approach, we identified ADAMTS13-derived peptides presented on
      HLA-DR for all 9 samples analyzed; ADAMTS13-derived peptides presented on HLA-DQ
      were identified in 4 out of 9 samples. We were able to confirm the presentation
      of the CUB2 domain-derived peptides FINVAPHAR and LIRDTHSLR on HLA-DR. In total,
      12 different core-peptide sequences were identified on HLA-DR and 8 on HLA-DQ.
      For HLA-DR11, several potential new core-peptides were found; 4 novel core
      peptides were exclusively identified on HLA-DQ. Furthermore, an in silico
      analysis was performed using the EpiMatrix and JanusMatrix tools to evaluate the
      eluted peptides, in the context of HLA-DR, for putative effector or regulatory T
      cell responses at the population level. The results from this study provide a
      basis for the identification of immuno-dominant epitopes on ADAMTS13 involved in
      the onset of acquired thrombotic thrombocytopenic purpura.

PMID- 29567782
TI  - miR-181a regulates erythroid enucleation via the regulation of Xpo7 expression.

PMID- 29567781
TI  - A novel regimen for relapsed/refractory adult acute myeloid leukemia using a
      KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI
      8485.
AB  - KMT2A partial tandem duplication occurs in approximately 5-10% of patients with
      acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type
      is epigenetically silenced in KMT2A partial tandem duplication; re-expression can
      be induced with DNA methyltransferase and/or histone deacetylase inhibitors in
      vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that
      epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem
      duplication-associated leukemogenesis and pharmacologic re-expression activates
      apoptotic mechanisms important for chemoresponse. We developed a regimen for this
      unique molecular subset, but due to relatively low frequency of KMT2A partial
      tandem duplication, this dose finding study was conducted in relapsed/refractory
      disease regardless of molecular subtype. Seventeen adults (< age 60) with
      relapsed/refractory acute myeloid leukemia were treated on study. Patients
      received decitabine 20 milligrams/meter2 daily on days 1-10 and vorinostat 400
      milligrams daily on days 5-10. Cytarabine was dose-escalated from 1.5
      grams/meter2 every 12 hours to 3 grams/meter2 every 12 hours on days 12, 14 and
      16. Two patients experienced dose limiting toxicities at dose level 1 due to
      prolonged myelosuppression. However, as both patients achieved complete remission
      after Day 42, the protocol was amended to adjust the definition of hematologic
      dose limiting toxicity. No further dose limiting toxicities were found. Six of 17
      patients achieved complete remission including 2 of 4 patients with KMT2A partial
      tandem duplication. Combination therapy with decitabine, vorinostat and
      cytarabine was tolerated in younger relapsed/refractory acute myeloid leukemia
      and should be explored further focusing on the KMT2A partial tandem duplication
      subset. (clinicaltrials.gov identifier 01130506).

PMID- 29567783
TI  - C/EBPgamma is dispensable for steady-state and emergency granulopoiesis.

PMID- 29567784
TI  - Treatment to suppression of focal lesions on positron emission tomography
      computed tomography is a therapeutic goal in newly diagnosed multiple myeloma.
AB  - Fluorine-18 fluorodeoxyglucose positron emission tomography with computed
      tomography attenuation correction (PET-CT) in myeloma can detect and enumerate
      focal lesions by the quantitative characterization of metabolic activity. The aim
      of this study was to determine the prognostic significance of the suppression of
      PET-CT activity at a number of time points post therapy initiation: day 7, post
      induction, post transplant, and at maintenance therapy. As part of the TT4-6
      trial series, 596 patients underwent baseline PET-CT and were evaluated serially
      during their disease course using peak standardized uptake values above
      background red marrow signal. We demonstrate that the presence of more than 3
      focal lesions at presentation identifies a group of patients with an adverse
      progression-free survival and overall survival. At day 7 of therapy, patients
      with complete focal lesion signal suppression revert to the same prognosis as
      those with no lesions at diagnosis. At later time points, the continued
      suppression of signal remains prognostically important. We conclude that for
      newly diagnosed patients with focal lesions, treatment until these lesions are
      suppressed is an important therapeutic goal as the prognosis of these patients is
      the same as those without lesions at diagnosis. (clinicaltrials.gov identifiers:
      00734877, 02128230, 00869232, 00871013).

PMID- 29567785
TI  - DNA polymerase nu gene expression influences fludarabine resistance in chronic
      lymphocytic leukemia independently of p53 status.
AB  - Alteration in the DNA replication, repair or recombination processes is a highly
      relevant mechanism of genomic instability. Despite genomic aberrations manifested
      in hematologic malignancies, such a defect as a source of biomarkers has been
      underexplored. Here, we investigated the prognostic value of expression of 82
      genes involved in DNA replication-repair-recombination in a series of 99 patients
      with chronic lymphocytic leukemia without detectable 17p deletion or TP53
      mutation. We found that expression of the POLN gene, encoding the specialized DNA
      polymerase nu (Pol nu) correlates with time to relapse after first-line therapy
      with fludarabine. Moreover, we found that POLN was the only gene up-regulated in
      primary patients' lymphocytes when exposed in vitro to proliferative and pro
      survival stimuli. By using two cell lines that were sequentially established from
      the same patient during the course of the disease and Pol nu knockout mouse
      embryonic fibroblasts, we reveal that high relative POLN expression is important
      for DNA synthesis and cell survival upon fludarabine treatment. These findings
      suggest that Pol nu could influence therapeutic resistance in chronic lymphocytic
      leukemia. (Patients' samples were obtained from the CLL 2007 FMP clinical trial
      registered at: clinicaltrials.gov identifer: 00564512).

PMID- 29567786
TI  - Germline JAK2 L611S mutation in a child with thrombocytosis.

PMID- 29567788
TI  - Role model: Ian Nesbitt.

PMID- 29567789
TI  - What have we learned about exfoliation syndrome since its discovery by John
      Lindberg 100 years ago?
AB  - Exfoliation syndrome (XFS) is a systemic disease with significant ocular
      manifestations, including glaucoma and cataract. The disease impacts close to 70
      million people globally and is now recognised as the most common identifiable
      cause of open-angle glaucoma. Since the discovery of XFS 100 years ago by Dr John
      G. Lindberg, there has been considerable advancement in understanding its
      pathogenesis and resulting clinical implications. The purpose of this paper is to
      summarise information regarding the epidemiology, pathophysiology, ocular
      manifestations and systemic associations of XFS with the objective of sharing
      clinical pearls to assist in early detection and enhanced management of patients.

PMID- 29567790
TI  - Full tendon medial transposition of lateral rectus with augmentation sutures in
      cases of complete third nerve palsy.
AB  - Management options in third nerve palsy are limited as four of the six
      extraocular muscles are involved. Surgery has to be tailored on a case-to-case
      basis. Aim of this retrospective case series is to report 1-year outcomes of a
      modified surgical technique entailing full tendon transposition of lateral rectus
      to medial rectus augmented with posterior fixation sutures in four patients with
      complete third nerve palsy. All four cases showed significant improvement of
      vertical and horizontal deviation with long-term stability of correction. Choice
      of route of full tendon augmented transposition of lateral rectus to medial
      rectus can aid in achieving good correction of the vertical misalignment in
      addition to horizontal correction.

PMID- 29567792
TI  - Prevalence of the optic disc anomalies in the adult South Indian population.
AB  - PURPOSE: To determine the prevalence of congenitally abnormal disc (all
      anomalies) in an adult population in southern India. METHODS: Subjects aged >=40
      years (n=6013) underwent a complete ophthalmic examination. Optic disc anomalies
      were diagnosed according to the definitions given in the article. RESULTS: Optic
      disc anomalies were found in 81 eyes of 66 (1.1%, 95% CIs 0.00834 to 0.01361)
      patients. The prevalence of each anomaly in the descending order was
      peripapillary myelinated nerve fibre (0.28%), epipapillary glial tissue on the
      optic disc (0.28%), peripapillary vascular loops (0.16%), tilted disc (0.09%),
      optic disc coloboma (0.08%), optic nerve hypoplasia (0.04%), optic disc pit
      (0.04%), optic disc pigmentation (0.03%), optic nerve head drusen (0.03%),
      Bergmeister's papilla (0.03%), optic disc pit and coloboma (0.01%). CONCLUSIONS:
      The prevalence of optic disc anomalies is 1.1% in the adult South Indian
      population.

PMID- 29567791
TI  - Baseline choroidal thickness as a short-term predictor of visual acuity
      improvement following antivascular endothelial growth factor therapy in branch
      retinal vein occlusion.
AB  - PURPOSE: To evaluate the association between subfoveal choroidal thickness (SFCT)
      and branch retinal vein occlusion (BRVO) eyes treated with antivascular
      endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective cohort
      study of treatment naive BRVO eyes treated with 3 monthly anti-VEGF injections.
      All patients received enhanced depth imaging spectral-domain optical coherence
      tomography scans to determine SFCT and central macular thickness (CMT). Baseline
      predictors (particularly SFCT) for functional response (best-corrected visual
      acuity (BCVA) gain >=2 lines) were assessed at 3 months using univariate and
      multivariate analyses. RESULTS: Forty eyes from 39 patients were included. Mean
      baseline SFCT was higher in functional responders (240.4+/-73.1 um), compared
      with both non-responders (193.3+/-63.6 um; p=0.036) and their corresponding
      fellow eye (202.2+/-67.1 um; p=0.022). A higher baseline SFCT (for every 100 um
      increase in SFCT) was found to be a positive predictor for functional response
      (regression coefficient: 1.1; p=0.03) on univariate analysis but not multivariate
      analysis. A worse baseline BCVA (for every 0.1 logMAR increase) was a positive
      predictor for visual improvement with an adjusted OR of 1.30 (95% CI 1.03 to
      1.63; p=0.0009) on multivariate analysis. CONCLUSIONS: Patients with BRVO with a
      worse initial BCVA are most likely to achieve visual improvement following anti
      VEGF therapy. Additionally, baseline SFCT may also help predict which patients
      with BRVO have favourable visual outcomes. Patients with an initial choroidal
      thickness thicker than their fellow eye are more likely to have short-term visual
      improvement following treatment.

PMID- 29567793
TI  - Corneal transplant follow-up study II (CTFS II): a prospective clinical trial to
      determine the influence of HLA class II matching on corneal transplant rejection:
      baseline donor and recipient characteristics.
AB  - PURPOSE: To describe a study to determine the influence of HLA class II matching
      on allograft rejection of high-risk, full-thickness corneal transplants. METHODS:
      A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary
      outcome measure of time to first clinically determined rejection episode. Tissue
      typing used DNA-based techniques. Corneas were allocated to patients with <=2
      human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation
      to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches. Transplants were
      to be followed up at 6 months and then annually on the anniversary of surgery for
      5 years. Power calculations estimated a sample size of 856 transplants to detect
      a 0.1 difference in probability of rejection at 1 year between HLA class II
      matched and mismatched transplants at the 5% level of significance with 80%
      power. RESULTS: To allow for loss to follow-up, 1133 transplants in 980 patients
      were accrued to the study between 3 September 1998 and 2 June 2011. 17% of
      transplants had 0 HLA-DR mismatches. The most frequent indication was bullous
      keratopathy, accounting for 27% of transplants and 54% of the transplants were
      regrafts. Median waiting time for a matched graft was 3 months. Donor and
      recipient characteristics were distributed evenly across the study groups.
      CONCLUSION: Recruitment to the CFS II has closed with 1077/1133 transplants
      meeting all the study criteria. Follow-up has been completed and final analysis
      of the data has started. TRIAL REGISTRATION NUMBER: ISRCTN25094892
      andUKCRNID9871, Pre-results.

PMID- 29567794
TI  - Early OCT angiography changes of type 1 CNV in exudative AMD treated with anti
      VEGF.
AB  - AIMS: To investigate, with optical coherence tomography angiography (OCTA), short
      term changes of type 1 choroidal neovascularisation (CNV), secondary to exudative
      age-related macular degeneration, after anti-vascular endothelial growth factor
      (VEGF) treatment. METHODS: Patients affected by type 1 CNV treated with
      intravitreal anti-VEGF were consecutively enrolled. All patients underwent OCTA
      examination before and 48 hours after anti-VEGF treatment. Quantitative and
      qualitative vascular and morphological macular changes were evaluated. RESULTS:
      Sixteen eyes were included (11 treated with aflibercept and 5 with ranibizumab).
      Both CNV mean area and pigment epithelium detachment significantly reduced
      (p=0.0004 and p=0.0007, respectively) after treatment. Cystoid macular oedema
      (four eyes) decreased in all cases. Neuroretinal detachment (13 eyes) decreased
      in 85% of cases (11 eyes). Fine CNV vessels density decreased in 75% (12 eyes),
      whereas larger CNV vessels density remained stable in 66.7% (10 eyes), choroidal
      flow void signal (7 eyes at baseline) increased in 42.9% (3 eyes) of them and
      remained stable in 57.1% (4 eyes). Interoperator reproducibility for OCT
      examination was good for all measurements (intraclass correlation
      coefficient>0.65). CONCLUSION: Early remodelling of type 1 CNV network after
      treatment may be non-invasively and reproducibly analysed by means of OCTA.
      Choroidal perfusion impairment, choroidal flow void signal, surrounding CNV may
      change during treatment.

PMID- 29567796
TI  - How an intrinsic ligand tunes the activity of a potassium channel.

PMID- 29567795
TI  - Dynamic rearrangement of the intrinsic ligand regulates KCNH potassium channels.
AB  - KCNH voltage-gated potassium channels (EAG, ERG, and ELK) play significant roles
      in neuronal and cardiac excitability. They contain cyclic nucleotide-binding
      homology domains (CNBHDs) but are not directly regulated by cyclic nucleotides.
      Instead, the CNBHD ligand-binding cavity is occupied by an intrinsic ligand,
      which resides at the intersubunit interface between the N-terminal eag domain and
      the C-terminal CNBHD. We show that, in Danio rerio ELK channels, this intrinsic
      ligand is critical for voltage-dependent potentiation (VDP), a process in which
      channel opening is stabilized by prior depolarization. We demonstrate that an
      exogenous peptide corresponding to the intrinsic ligand can bind to and regulate
      zebrafish ELK channels. This exogenous intrinsic ligand inhibits the channels
      before VDP and potentiates the channels after VDP. Furthermore, using transition
      metal ion fluorescence resonance energy transfer and a fluorescent noncanonical
      amino acid L-Anap, we show that there is a rearrangement of the intrinsic ligand
      relative to the CNBHD during VDP. We propose that the intrinsic ligand switches
      from antagonist to agonist as a result of a rearrangement of the eag domain-CNBHD
      interaction during VDP.

PMID- 29567797
TI  - Human ALPI deficiency causes inflammatory bowel disease and highlights a key
      mechanism of gut homeostasis.
AB  - Herein, we report the first identification of biallelic-inherited mutations in
      ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated
      patients. ALPI encodes for intestinal phosphatase alkaline, a brush border
      metalloenzyme that hydrolyses phosphate from the lipid A moiety of
      lipopolysaccharides and thereby drastically reduces Toll-like receptor 4 agonist
      activity. Prediction tools and structural modelling indicate that all mutations
      affect critical residues or inter-subunit interactions, and heterologous
      expression in HEK293T cells demonstrated that all ALPI mutations were loss of
      function. ALPI mutations impaired either stability or catalytic activity of ALPI
      and rendered it unable to detoxify lipopolysaccharide-dependent signalling.
      Furthermore, ALPI expression was reduced in patients' biopsies, and ALPI activity
      was undetectable in ALPI-deficient patient's stool. Our findings highlight the
      crucial role of ALPI in regulating host-microbiota interactions and restraining
      host inflammatory responses. These results indicate that ALPI mutations should be
      included in screening for monogenic causes of inflammatory bowel diseases and lay
      the groundwork for ALPI-based treatments in intestinal inflammatory disorders.

PMID- 29567798
TI  - Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final
      5-year results of the phase 2 PACE trial.
AB  - Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR
      ABL1T315I The pivotal phase 2 Ponatinib Ph+ ALL and CML Evaluation (PACE) trial
      evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily
      in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome
      positive acute lymphoblastic leukemia (ALL) resistant/intolerant to dasatinib or
      nilotinib, or with BCR-ABL1T315I This analysis focuses on chronic-phase CML (CP
      CML) patients (n = 270) with 56.8-month median follow-up. Among 267 evaluable
      patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major
      molecular response (MMR), and 4.5-log molecular response, respectively. The
      probability of maintaining MCyR for 5 years was 82% among responders. Dose
      reductions were implemented in October 2013 to decrease the risk of arterial
      occlusive events (AOEs); >=90% of CP-CML patients who had achieved MCyR or MMR
      maintained response 40 months after elective dose reductions. Estimated 5-year
      overall survival was 73%. In CP-CML patients, the most common treatment-emergent
      adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%),
      headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence
      of AOEs in CP-CML patients increased over time to 31%, while the exposure
      adjusted incidence of new AOEs (15.8 and 4.9 per 100 patient-years in years 1 and
      5, respectively) did not increase over time. These final PACE results demonstrate
      ponatinib provides durable and clinically meaningful responses, irrespective of
      dose reductions, in this population of heavily pretreated CP-CML patients. This
      trial was registered at www.clinicaltrials.gov as #NCT01207440.

PMID- 29567799
TI  - Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non
      Hodgkin lymphoma.
AB  - In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR)
      promotes multiple oncogenic signals, which are essential for tumor proliferation.
      Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is
      therapeutically effective only in a subgroup of patients with DLBCL. Here, we
      used lymphoma cells isolated from patients with DLBCL to measure the effects of
      targeted therapies on BCR signaling and to anticipate response. In lymphomas
      resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor
      dependencies from alternative oncogenic signals downstream of the BCR, converging
      on MYC upregulation. To completely ablate the activity of the BCR, we genetically
      and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and
      BLK, which are responsible for the propagation of the BCR signal. Inhibition of
      these kinases strongly reduced tumor growth in xenografts and cell lines derived
      from patients with DLBCL independent of their molecular subtype, advancing the
      possibility to be relevant therapeutic targets in broad and diverse groups of
      DLBCL patients.

PMID- 29567801
TI  - Death of baby from hyperinsulinaemic hypoglycaemia prompts safety upgrade at
      Barts trust.

PMID- 29567800
TI  - To Spinal Tap or Not To Spinal Tap, That Is the Question.

PMID- 29567802
TI  - Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent
      anorectal infection in men who have sex with men in western Sydney.
AB  - OBJECTIVES: We aimed to estimate the prevalence of Mycoplasma genitalium
      infection and of mutations linked to macrolide resistance using the
      ResistancePlus MG assay (SpeeDx, Sydney, New South Wales, Australia) in first
      void urine (FVU), anorectal and oropharyngeal samples from men who have sex with
      men (MSM) attending Western Sydney Sexual Health Centre (WSSHC). METHODS:
      Consecutive symptomatic and asymptomatic MSM attending for STI testing were
      prospectively enrolled. M. genitalium testing using the ResistancePlus MG assay
      was performed on FVU, anorectal and oropharyngeal samples routinely collected for
      Chlamydia trachomatis and Neisseria gonorrhoeae assays. RESULTS: Overall, the
      prevalence of M. genitalium infection in the study group was 13.4% (68/508). Most
      (79.4%, 54/68) M. genitalium harboured macrolide resistance mutations (87.5% of
      urethral and 75.6% of anorectal infections). The anorectum was the most commonly
      infected site (45/505, 8.9%), followed by the urethra (24/508, 4.7%). No
      oropharyngeal M. genitalium infections were detected (0/508). Most of the
      anorectal (93.3%) and urethral (79.2%) infections were asymptomatic.MSM who were
      taking HIV pre-exposure prophylaxis (PrEP) were twice as likely to be infected
      with M. genitalium compared with MSM who were not on PrEP (OR 2.1, 95% CI 1.3 to
      3.6; P=0.0041). Always using condoms for anal sex in the last 3 months was
      protective of infection (OR 0.8, 95% CI 0.6 to 1.0; P=0.0186). CONCLUSIONS: We
      demonstrated a high prevalence of M. genitalium and very high levels of macrolide
      resistance among MSM attending WSSHC. Our findings support the routine use of an
      assay to detect macrolide resistance mutations in M. genitalium infections. This
      will ensure, in regions or populations with high rates of macrolide resistance
      among M. genitalium strains, that first-line treatment with azithromycin will
      only be used if a macrolide-sensitive strain is identified.

PMID- 29567803
TI  - Canadian Child Safety Report Card: a comparison of injury prevention practices
      across provinces.
AB  - BACKGROUND: Injury prevention report cards that raise awareness about the
      preventability of childhood injuries have been published by the European Child
      Safety Alliance and the WHO. These report cards highlight the variance in injury
      prevention practices around the world. Policymakers and stakeholders have
      identified research evidence as an important enabler to the enactment of injury
      legislation. In Canada, there is currently no childhood injury report card that
      ranks provinces on injury rates or evidence-based prevention policies. METHODS:
      Three key measures, with five metrics, were used to compare provinces on
      childhood injury prevention rates and strategies, including morbidity, mortality
      and policy indicators over time (2006-2012). Nine provinces were ranked on five
      metrics: (1) population-based hospitalisation rate/100 000; (2) per cent change
      in hospitalisation rate/100 000; (3) population-based mortality rate/100 000; (4)
      per cent change in mortality rate/100 000; (5) evidence-based policy assessment.
      RESULTS: Of the nine provinces analysed, British Columbia ranked highest in
      Canada and Saskatchewan lowest. British Columbia had a morbidity and mortality
      rate that was close to the Canadian average and decreased over the study period.
      British Columbia also had a number of injury prevention policies and legislation
      in place that followed best practice guidelines. Saskatchewan had a higher rate
      of injury hospitalisation and death; however, Saskatchewan's rate decreased over
      time. Saskatchewan had a number of prevention policies in place but had not
      enacted bicycle helmet legislation. CONCLUSIONS: Future preventative efforts
      should focus on harmonising policies across all provinces in Canada that reflect
      evidence-based best practices.

PMID- 29567804
TI  - Primary Traumatic Axonopathy in Mice Subjected to Impact Acceleration: A
      Reappraisal of Pathology and Mechanisms with High-Resolution Anatomical Methods.
AB  - Traumatic axonal injury (TAI) is a common neuropathology in traumatic brain
      injury and is featured by primary injury to axons. Here, we generated TAI with
      impact acceleration of the head in male Thy1-eYFP-H transgenic mice in which
      specific populations of neurons and their axons are labeled with yellow
      fluorescent protein. This model results in axonal lesions in multiple axonal
      tracts along with blood-brain barrier disruption and neuroinflammation. The
      corticospinal tract, a prototypical long tract, is severely affected and is the
      focus of this study. Using optimized CLARITY at single-axon resolution, we
      visualized the entire corticospinal tract volume from the pons to the cervical
      spinal cord in 3D and counted the total number of axonal lesions and their
      progression over time. Our results divulged the presence of progressive traumatic
      axonopathy that was maximal at the pyramidal decussation. The perikarya of
      injured corticospinal neurons atrophied, but there was no evidence of neuronal
      cell death. We also used CLARITY at single-axon resolution to explore the role of
      the NMNAT2-SARM1 axonal self-destruction pathway in traumatic axonopathy. When we
      interfered with this pathway by genetically ablating SARM1 or by pharmacological
      strategies designed to increase levels of Nicotinamide (Nam), a feedback
      inhibitor of SARM1, we found a significant reduction in the number of axonal
      lesions early after injury. Our findings show that high-resolution
      neuroanatomical strategies reveal important features of TAI with biological
      implications, especially the progressive axonopathic nature of TAI and the role
      of the NMNAT2-SARM1 pathway in the early stages of axonopathy.SIGNIFICANCE
      STATEMENT In the first systematic application of novel high-resolution
      neuroanatomical tools in neuropathology, we combined CLARITY with 2-photon
      microscopy, optimized for detection of single axonal lesions, to reconstruct the
      injured mouse brainstem in a model of traumatic axonal injury (TAI) that is a
      common pathology associated with traumatic brain injury. The 3D reconstruction of
      the corticospinal tract at single-axon resolution allowed for a more advanced
      level of qualitative and quantitative understanding of TAI. Using this model, we
      showed that TAI is an axonopathy with a prominent role of the NMNAT2-SARM1
      molecular pathway, that is also implicated in peripheral neuropathy. Our results
      indicate that high-resolution anatomical models of TAI afford a level of detail
      and sensitivity that is ideal for testing novel molecular and biomechanical
      hypotheses.

PMID- 29567805
TI  - Editorial licence: what gets published and why.

PMID- 29567807
TI  - Structure of a prehandover mammalian ribosomal SRP.SRP receptor targeting
      complex.
AB  - Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum
      (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it
      to the SRP receptor (SR) on the ER membrane followed by the transfer of the
      signal sequence to the translocon. Here, we present the cryo-electron microscopy
      structure of the mammalian translating ribosome in complex with SRP and SR in a
      conformation preceding signal sequence handover. The structure visualizes all
      eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing
      this conformation by forming a large protein assembly at the distal site of SRP
      RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis
      of SRP.SR is delayed at this stage, possibly to provide a time window for signal
      sequence handover to the translocon.

PMID- 29567808
TI  - Legacy nitrogen may prevent achievement of water quality goals in the Gulf of
      Mexico.
AB  - In August 2017, the Gulf of Mexico's hypoxic zone was declared to be the largest
      ever measured. It has been estimated that a 60% decrease in watershed nitrogen
      (N) loading may be necessary to adequately reduce eutrophication in the Gulf.
      However, to date there has been no rigorous assessment of the effect of N
      legacies on achieving water quality goals. In this study, we show that even if
      agricultural N use became 100% efficient, it would take decades to meet target N
      loads due to legacy N within the Mississippi River basin. Our results suggest
      that both long-term commitment and large-scale changes in agricultural management
      practices will be necessary to decrease Mississippi N loads and to meet current
      goals for reducing the size of the Gulf hypoxic zone.

PMID- 29567809
TI  - The threshold for conscious report: Signal loss and response bias in visual and
      frontal cortex.
AB  - Why are some visual stimuli consciously detected, whereas others remain
      subliminal? We investigated the fate of weak visual stimuli in the visual and
      frontal cortex of awake monkeys trained to report stimulus presence. Reported
      stimuli were associated with strong sustained activity in the frontal cortex, and
      frontal activity was weaker and quickly decayed for unreported stimuli.
      Information about weak stimuli could be lost at successive stages en route from
      the visual to the frontal cortex, and these propagation failures were confirmed
      through microstimulation of area V1. Fluctuations in response bias and
      sensitivity during perception of identical stimuli were traced back to
      prestimulus brain-state markers. A model in which stimuli become consciously
      reportable when they elicit a nonlinear ignition process in higher cortical areas
      explained our results.

PMID- 29567810
TI  - Two-billion-year-old evaporites capture Earth's great oxidation.
AB  - Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic
      era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed
      Earth's surface, but few quantitative constraints exist on this important
      transition. This study describes the sedimentology, mineralogy, and geochemistry
      of a 2-billion-year-old, ~800-meter-thick evaporite succession from the Onega
      Basin in Russian Karelia. The deposit consists of a basal unit dominated by
      halite (~100 meters) followed by units dominated by anhydrite-magnesite (~500
      meters) and dolomite-magnesite (~200 meters). The evaporite minerals robustly
      constrain marine sulfate concentrations to at least 10 millimoles per kilogram of
      water, representing an oxidant reservoir equivalent to more than 20% of the
      modern ocean-atmosphere oxidizing capacity. These results show that substantial
      amounts of surface oxidant accumulated during this critical transition in Earth's
      oxygenation.

PMID- 29567811
TI  - Epigenome-wide SRC-1-Mediated Gene Silencing Represses Cellular Differentiation
      in Advanced Breast Cancer.
AB  - Purpose: Despite the clinical utility of endocrine therapies for estrogen
      receptor-positive (ER) breast cancer, up to 40% of patients eventually develop
      resistance, leading to disease progression. The molecular determinants that drive
      this adaptation to treatment remain poorly understood. Methylome aberrations
      drive cancer growth yet the functional role and mechanism of these epimutations
      in drug resistance are poorly elucidated.Experimental Design: Genome-wide multi
      omics sequencing approach identified a differentially methylated hub of
      prodifferentiation genes in endocrine resistant breast cancer patients and cell
      models. Clinical relevance of the functionally validated methyl-targets was
      assessed in a cohort of endocrine-treated human breast cancers and patient
      derived ex vivo metastatic tumors.Results: Enhanced global hypermethylation was
      observed in endocrine treatment resistant cells and patient metastasis relative
      to sensitive parent cells and matched primary breast tumor, respectively. Using
      paired methylation and transcriptional profiles, we found that SRC-1-dependent
      alterations in endocrine resistance lead to aberrant hypermethylation that
      resulted in reduced expression of a set of differentiation genes. Analysis of ER
      positive endocrine-treated human breast tumors (n = 669) demonstrated that low
      expression of this prodifferentiation gene set significantly associated with poor
      clinical outcome (P = 0.00009). We demonstrate that the reactivation of these
      genes in vitro and ex vivo reverses the aggressive phenotype.Conclusions: Our
      work demonstrates that SRC-1-dependent epigenetic remodeling is a 'high level'
      regulator of the poorly differentiated state in ER-positive breast cancer.
      Collectively these data revealed an epigenetic reprograming pathway, whereby
      concerted differential DNA methylation is potentiated by SRC-1 in the endocrine
      resistant setting. Clin Cancer Res; 24(15); 3692-703. (c)2018 AACR.

PMID- 29567812
TI  - False-Positive Plasma Genotyping Due to Clonal Hematopoiesis.
AB  - Purpose: Plasma cell-free DNA (cfDNA) genotyping is increasingly used in cancer
      care, but assay accuracy has been debated. Because most cfDNA is derived from
      peripheral blood cells (PBC), we hypothesized that nonmalignant mutations
      harbored by hematopoietic cells (clonal hematopoiesis, CH) could be a cause of
      false-positive plasma genotyping.Experimental Design: We identified patients with
      advanced non-small cell lung cancer (NSCLC) with KRAS, JAK2, or TP53 mutations
      identified in cfDNA. With consent, PBC DNA was tested using droplet digital PCR
      (ddPCR) or next-generation sequencing (NGS) to test for CH-derived
      mutations.Results: We first studied plasma ddPCR results from 58 patients with
      EGFR-mutant NSCLC. Two had KRAS G12X detected in cfDNA, and both were present in
      PBC, including one where the KRAS mutation was detected serially for 20 months.
      We then studied 143 plasma NGS results from 122 patients with NSCLC and
      identified 5 JAK2 V617F mutations derived from PBC. In addition, 108 TP53
      mutations were detected in cfDNA; for 33 of the TP53 mutations, PBC and tumor NGS
      were available for comparison, and 5 were present in PBC but absent in tumor,
      consistent with CH.Conclusions: We find that most JAK2 mutations, some TP53
      mutations, and rare KRAS mutations detected in cfDNA are derived from CH not
      tumor. Clinicians ordering plasma genotyping must be prepared for the possibility
      that mutations detected in plasma, particularly in genes mutated in CH, may not
      represent true tumor genotype. Efforts to use plasma genotyping for cancer
      detection may need paired PBC genotyping so that CH-derived mutations are not
      misdiagnosed as occult malignancy. Clin Cancer Res; 24(18); 4437-43. (c)2018
      AACRSee related commentary by Bauml and Levy, p. 4352.

PMID- 29567813
TI  - Changes in Parental Hopes for Seriously Ill Children.
AB  - BACKGROUND: Hopes of parents of children with serious illness play an important
      role in decision-making and coping. Little is known about how parent hopes change
      over time. We describe the changes in parent hopes across multiple domains and
      time intervals, examine hopes in a subgroup of parents whose child died, and
      explore the maintenance of domains over time. METHODS: In a mixed-methods
      prospective cohort study on decision-making, parents of seriously ill children
      reported demographic characteristics and hopes at baseline and reported any
      changes in hopes at 4-, 8-, 12-, 16-, and 20-month follow-up visits. Hopes were
      coded into 9 domains. Hope changes and domain changes were identified for each
      parent at each visit. RESULTS: One hundred and ninety-nine parents of 158
      patients most often reported hopes in the domains of quality of life (75%),
      physical body (69%), future well-being (47%), and medical care (34%). Hope
      percentages increased over time for quality of life (84%), future well-being
      (64%), and broader meaning (21%). The hope domains reported by parents of
      children who died were similar to the rest of the sample. The majority of parents
      who completed 5 to 6 follow-up visits changed at least 1 domain. At the
      individual parent level, some domains revealed considerable change over time,
      whereas other domains were stable among a subset of parents. CONCLUSIONS: The
      specific hopes and overall areas of hope of parents of seriously ill children
      vary over time, although most hopes fall within 4 major areas. Accordingly,
      clinicians should regularly check with parents about their current hopes.

PMID- 29567814
TI  - Motor Impairment Trends in Extremely Preterm Children: 1991-2005.
AB  - BACKGROUND: There are increasing numbers of surviving children who were born
      extremely preterm (EP; gestational age <28 weeks) or extremely low birth weight
      (ELBW; birth weight <1000 g). Our objective in this study was to compare the
      rates of motor impairment at 8 years of age between 3 cohorts of EP and/or ELBW
      and term-born children to establish if motor impairment rates are changing over
      time. METHODS: All children born EP and/or ELBW in the calendar years of 1991
      1992, 1997, and 2005 in Victoria, Australia, were recruited at birth. Randomly
      selected normal birth weight (>2499 g) and term-born controls were matched for
      expected date of birth, sex, and sociodemographic status. At 8 years' corrected
      age, motor impairment was defined as cerebral palsy (CP) or a score less than the
      fifth centile on the Movement Assessment Battery for Children for the 1991-1992
      and 1997 cohorts and less than or equal to the fifth centile on the Movement
      Assessment Battery for Children-Second Edition for the 2005 cohort. RESULTS:
      Motor impairment was more likely in children born EP and/or ELBW compared with
      children born at term for all epochs. There was a significant increase in motor
      impairment in EP and/or ELBW children over the 3 eras, from 23% in 1991-1992 and
      26% in 1997 to 37% in 2005 (chi2trend = 10.2; P = .001). This was due to an
      increase in non-CP motor impairment (13% in 1991 to 1992; 15% in 1997; 26% in
      2005; chi2trend = 12.5; P < .001), not CP (11% in 1991 to 1992; 11% in 1997; 12%
      in 2005). CONCLUSIONS: The rate of motor impairment in EP and/or ELBW children
      assessed at 8 years of age increased between eras, an increase caused by non-CP
      motor impairment.

PMID- 29567815
TI  - Erratum for Chang et al., "Whole-Genome Characterization of Bacillus cereus
      Associated with Specific Disease Manifestations".

PMID- 29567816
TI  - Correction for Wang et al., "Immunoprofiling of the Tryptophan-Rich Antigen
      Family in Plasmodium vivax".

PMID- 29567817
TI  - Implementation of Learning from Excellence initiative in a neonatal intensive
      care unit.

PMID- 29567818
TI  - Unexpected heart block in the delivery room: the utility of ECG monitoring.

PMID- 29567819
TI  - Insights into the Psychology of Trauma Should Inform the Practice of Oncology.

PMID- 29567820
TI  - Prognostic Factors and Efficacy of First-Line Chemotherapy in Patients with
      Advanced Thymic Carcinoma: A Retrospective Analysis of 286 Patients from NEJ023
      Study.
AB  - BACKGROUND: The prognostic factors and the efficacy of first-line chemotherapy
      remain unclear in patients with advanced thymic carcinoma. MATERIALS AND METHODS:
      We conducted a multi-institutional retrospective study named NEJ023 for patients
      with advanced thymic carcinoma. All patients without any indication of curative
      treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions of
      the North East Japan Study Group. RESULTS: A total of 286 patients with advanced
      thymic carcinoma were analyzed. First-line chemotherapy included platinum-based
      doublets in 62.2% of the patients, monotherapy in 3.5%, and other multidrug
      chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide
      [ADOC]) in 34.3%. The median follow-up period was 55.5 months, and the median
      overall survival (OS) from the start of first-line chemotherapy was 30.7 months
      (95% confidence interval, 25.9-35.9 months). There was no significant difference
      in OS among different first-line chemotherapy regimens (e.g., between
      carboplatin/paclitaxel and ADOC, median OS: 27.8 vs. 29.9 months). Masaoka-Koga
      stage IVa and volume reduction surgery were favorable prognostic factors for OS
      in the multivariate analysis using the Cox proportional hazards model.
      CONCLUSION: The efficacy of each first-line chemotherapy regimen for advanced
      thymic carcinoma did not vary significantly. Our results might support the
      adequacy of the use of carboplatin/paclitaxel as first-line chemotherapy for
      these patients. IMPLICATIONS FOR PRACTICE: Because of its rarity, there is
      limited information about prognostic factors and efficacy of chemotherapy in
      patients with advanced thymic carcinoma. This is the largest data set for those
      patients treated with chemotherapy. This study suggests there is no significant
      difference in efficacy between carboplatin/paclitaxel and
      cisplatin/doxorubicin/vincristine/cyclophosphamide for advanced thymic carcinoma.
      This result can support the adequacy of the selection of platinum doublets as
      treatment for those patients, rather than anthracycline-based multidrug regimen.

PMID- 29567821
TI  - Costs of Cancer Care Across the Disease Continuum.
AB  - PURPOSE: The aim of this study was to estimate Medicare payments for cancer care
      during the initial, continuing, and end-of-life phases of care for 10
      malignancies and to examine variation in expenditures according to patient
      characteristics and cancer severity. MATERIALS AND METHODS: We used linked
      Surveillance, Epidemiology and End Results-Medicare data to identify patients
      aged 66-99 years who were diagnosed with one of the following 10 cancers:
      prostate, bladder, esophageal, pancreatic, lung, liver, kidney, colorectal,
      breast, or ovarian, from 2007 through 2012. We attributed payments for each
      patient to a phase of care (i.e., initial, continuing, or end of life), based on
      time from diagnosis until death or end of study interval. We summed payments for
      all claims attributable to the primary cancer diagnosis and analyzed the overall
      and phase-based costs and then by differing demographics, cancer stage,
      geographic region, and year of diagnosis. RESULTS: We identified 428,300 patients
      diagnosed with one of the 10 malignancies. Annual payments were generally highest
      during the initial phase. Mean expenditures across cancers were $14,381 during
      the initial phase, $2,471 for continuing, and $13,458 at end of life. Payments
      decreased with increasing age. Black patients had higher payments for four of
      five cancers with statistically significant differences. Stage III cancers posed
      the greatest annual cost burden for four cancer types. Overall payments were
      stable across geographic region and year. CONCLUSION: Considerable differences
      exist in expenditures across phases of cancer care. By understanding the drivers
      of such payment variations across patient and tumor characteristics, we can
      inform efforts to decrease payments and increase quality, thereby reducing the
      burden of cancer care. IMPLICATIONS FOR PRACTICE: Considerable differences exist
      in expenditures across phases of cancer care. There are further differences by
      varying patient characteristics. Understanding the drivers of such payment
      variations across patient and tumor characteristics can inform efforts to
      decrease costs and increase quality, thereby reducing the burden of cancer care.

PMID- 29567822
TI  - Families' Sense of Abandonment When Patients Are Referred to Hospice.
AB  - BACKGROUND: Terminally ill patients with cancer and their families may have a
      sense of abandonment when they are referred to hospice. This study aimed to
      clarify the prevalence of families' sense of abandonment, explore the association
      between the sense of abandonment and the oncologists' behaviors, and investigate
      the association between the sense of abandonment and the families' depression and
      complicated grief. PATIENTS AND METHODS: This was part of a nationwide self
      reported questionnaire survey of bereaved families of patients with cancer who
      died in inpatient hospices. We sent questionnaires to 947 bereaved families of
      patients with cancer who died in 133 certified hospices between May 2012 and
      January 2014. RESULTS: Among 707 responses obtained, a total of 189 (26.7%)
      families felt abandoned. The factors significantly associated with a greater
      sense of abandonment were that the oncologists said there was nothing more to do
      for the patient, the patient's age of less than 60 years, and being the patient's
      spouse. The factors significantly associated with a lower sense of abandonment
      were that the oncologists reassured the patients that they had received the best
      anticancer treatment, that the oncologists recommended hospices as one potential
      choice rather than mandatory, and that a palliative care team provided care.
      Families with a sense of abandonment had higher scores on the Patient Health
      Questionnaire-9 (p = .096) and Brief Grief Questionnaire (p < .001). CONCLUSION:
      Approximately a quarter of bereaved families had a sense of abandonment, which
      was associated with a higher rate of complicated grief. Oncologists may reduce
      the sense of abandonment by reassuring that the patients received the best
      anticancer treatment, recommending hospices as a potential choice rather than as
      mandatory, and by not saying there is nothing that can be done for the patients.
      IMPLICATIONS FOR PRACTICE: This self-reported questionnaire study investigated
      the prevalence of families' feelings of abandonment when they were referred to
      hospice care, focusing on the association of sense of abandonment and the
      behavior of their physicians. Nearly a quarter of families felt abandoned by the
      referral to hospice, and the behavior of some oncologists was associated with the
      sense of abandonment.

PMID- 29567823
TI  - Cervical Cancer in Ethiopia: The Effect of Adherence to Radiotherapy on Survival.
AB  - BACKGROUND: Discontinuation of radiotherapy (RT) for cervical cancer (CC) in sub
      Saharan Africa is common because of patient- and health service-related reasons.
      This analysis describes toxicities and the effect of adherence on survival.
      MATERIALS AND METHODS: A total of 788 patients with CC (2008-2012) who received
      RT at Addis Ababa University Hospital were included. External beam RT without
      brachytherapy was performed according to local guidelines. We previously
      described survival and prognostic factors. Now we analyzed adherence and survival
      according to total doses received. Adjustment via multivariate cox regression
      analysis was done. RESULTS: One-year overall survival (OS) after radical RT (n =
      180) for International Federation of Gynecology and Obstetrics (FIGO) stages IIA
      IIIA was 89% for discontinuation (<72 Gy) and 96% for adherence (>=72 Gy; hazard
      ratio [HR], 1.3; 95% confidence interval [CI], 0.5-3.3). One-year OS after
      nonradical RT (n = 389) for FIGO stages IIIB-IVA was 71% for discontinuation (<40
      Gy) and 87% for adherence (44-50 Gy; HR, 3.1; 95% CI, 1.4-6.9). One-year OS for
      FIGO stages IIIB-IVB (n = 219) after one compared with two or more palliative
      single fractions of 10 Gy were 14% and 73% respectively (HR, 7.3; 95% CI, 3.3
      16). Reasons for discontinuation were toxicities, economic background, and RT
      machine breakdown. Grade 1-2 late toxicities were common (e.g., 30% proctitis,
      22% incontinence). Grade 3 early and late toxicities were seen in 5% and 10%
      respectively; no grade 4 toxicities occurred. CONCLUSION: Patients who adhered to
      guideline-conforming RT had optimum survival. Better supportive care,
      brachytherapy to reduce toxicities, socioeconomic support, and additional
      radiation capacities could contribute to better adherence and survival.
      IMPLICATIONS FOR PRACTICE: This study presents the effect of adherence on
      survival of 788 patients with cervical cancer receiving external beam
      radiotherapy without brachytherapy in Ethiopia. Discontinuation of planned
      radiotherapy according to local guidelines considerably reduced survival for all
      International Federation of Gynecology and Obstetrics (FIGO) stages treated
      (hazard ratios were 1.3, 3.1, and 7.3 for FIGO stages IIA-IIIA and IIIB-IVA and
      the palliative approach, respectively). Early toxicity (5% grade 3) should be
      treated to improve adherence. Economic difficulties and machine breakdown should
      also be addressed to reduce discontinuation and improve survival.

PMID- 29567824
TI  - Serial Troponin for Early Detection of Nivolumab Cardiotoxicity in Advanced Non
      Small Cell Lung Cancer Patients.
AB  - BACKGROUND: Rare cases of severe myocarditis are reported during treatment with
      nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the
      diagnostic workup of many cardiac disorders, including myocarditis. This study
      investigates the role of troponin to assess cardiac involvement during nivolumab
      therapy for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We
      evaluated 59 NSCLC patients, analyzing serum samples collected within a
      translational research study. Troponin above the upper normal limit (0.046 ng/mL)
      was defined as Tn+, whereas normal but detectable troponin (0.015-0.045) was
      defined as Tndet. Troponin alterations were interpreted on the grounds of the
      following elements: peak values and time curve, cardiac comorbidities, signs and
      symptoms coincident to troponin elevation, ECG, echocardiography, and disease
      progression. RESULTS: No patient had cardiovascular events. Among 362 available
      blood samples, Tn+ (max 0.317 ng/mL) was found in 13 determinations belonging to
      6 patients. Seven other patients had isolated Tndet. In five patients, Tn+ was
      attributed to cardiac comorbidities, disease progression, or worsening clinical
      status. One patient without cardiac history and in good clinical condition had a
      sustained troponin increase-soon after the start of therapy-and after careful
      evaluation of all relevant elements, it was interpreted as a marker of nivolumab
      related subclinical myocarditis. CONCLUSION: Tn+ may occur in NSCLC patients
      treated with nivolumab, but in most cases it does not indicate nivolumab
      cardiotoxicity. In some cases, however, a careful interpretation of troponin
      alteration, especially at the beginning of therapy, enables identification of
      subclinical myocarditis, thus allowing early cardiac treatment. IMPLICATIONS FOR
      PRACTICE: Myocarditis is a rare but serious adverse event of immune checkpoint
      blockade with nivolumab, which needs to be recognized as soon as possible. This
      article suggests that troponin, a user-friendly biomarker of myocardial
      cytotoxicity, might be useful for early detection of immune-mediated myocarditis.
      However, because troponin abnormalities might also be related to a number of
      conditions capable of causing myocardial oxygen demand-supply mismatch, a careful
      cardiac assessment should be performed in non-small cell lung cancer patients in
      order to properly interpret any troponin increase. According to the available
      evidence, monitoring troponin during the first weeks of treatment can be
      considered reasonable.

PMID- 29567825
TI  - The Emerging Impact of Social Media on Cancer Patient Education in Japan.

PMID- 29567826
TI  - Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A
      EURECCA International Comparison.
AB  - BACKGROUND: Colon cancer in older patients represents a major public health
      issue. As older patients are hardly included in clinical trials, the optimal
      treatment of these patients remains unclear. The present international EURECCA
      comparison explores possible associations between treatment and survival outcomes
      in elderly colon cancer patients. SUBJECTS, MATERIALS, AND METHODS: National data
      from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well
      as a multicenter surgery cohort from Germany. Patients aged 80 years and older,
      diagnosed with colon cancer between 2001 and 2010, were included. The study
      interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of
      surgical treatment and chemotherapy within a country and its relation to relative
      survival were calculated for each time frame. RESULTS: Overall, 50,761 patients
      were included. At least 94% of patients with stage II and III colon cancer
      underwent surgical removal of the tumor. For stage II-IV, the proportion of
      chemotherapy after surgery was highest in Belgium and lowest in The Netherlands
      and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway.
      For stage III, a better adjusted relative survival between 2007 and 2010 was
      observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence
      interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96)
      compared with Belgium. CONCLUSION: There is substantial variation in the rate of
      treatment and survival between countries for patients with colon cancer aged 80
      years or older. Despite higher prescription of adjuvant chemotherapy, poorer
      survival outcomes were observed in Belgium. No clear linear pattern between the
      proportion of chemotherapy and better adjusted relative survival was observed.
      IMPLICATIONS FOR PRACTICE: With the increasing growth of the older population,
      clinicians will be treating an increasing number of older patients diagnosed with
      colon cancer. No clear linear pattern between adjuvant chemotherapy and better
      adjusted relative survival was observed. Future studies should also include data
      on surgical quality.

PMID- 29567827
TI  - Strengthening research in the NHS.

PMID- 29567828
TI  - Vote on legalising assisted dying in Guernsey is due in months.

PMID- 29567831
TI  - The influence of bat echolocation call duration and timing on auditory encoding
      of predator distance in noctuoid moths.
AB  - Animals co-occur with multiple predators, making sensory systems that can encode
      information about diverse predators advantageous. Moths in the families Noctuidae
      and Erebidae have ears with two auditory receptor cells (A1 and A2) used to
      detect the echolocation calls of predatory bats. Bat communities contain species
      that vary in echolocation call duration, and the dynamic range of A1 is limited
      by the duration of sound, suggesting that A1 provides less information about bats
      with shorter echolocation calls. To test this hypothesis, we obtained intensity
      response functions for both receptor cells across many moth species for sound
      pulse durations representing the range of echolocation call durations produced by
      bat species in northeastern North America. We found that the threshold and
      dynamic range of both cells varied with sound pulse duration. The number of A1
      action potentials per sound pulse increases linearly with increasing amplitude
      for long-duration pulses, saturating near the A2 threshold. For short sound
      pulses, however, A1 saturates with only a few action potentials per pulse at
      amplitudes far lower than the A2 threshold for both single sound pulses and pulse
      sequences typical of searching or approaching bats. Neural adaptation was only
      evident in response to approaching bat sequences at high amplitudes, not search
      phase sequences. These results show that, for short echolocation calls, a large
      range of sound levels cannot be coded by moth auditory receptor activity,
      resulting in no information about the distance of a bat, although differences in
      activity between ears might provide information about direction.

PMID- 29567829
TI  - The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and
      Adaptive Immune Suppression.
AB  - We found that the cancerous pancreas harbors a markedly more abundant microbiome
      compared with normal pancreas in both mice and humans, and select bacteria are
      differentially increased in the tumorous pancreas compared with gut. Ablation of
      the microbiome protects against preinvasive and invasive pancreatic ductal
      adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but
      not controls, reverses tumor protection. Bacterial ablation was associated with
      immunogenic reprogramming of the PDA tumor microenvironment, including a
      reduction in myeloid-derived suppressor cells and an increase in M1 macrophage
      differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell
      activation. Bacterial ablation also enabled efficacy for checkpoint-targeted
      immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA
      microbiome generated a tolerogenic immune program by differentially activating
      select Toll-like receptors in monocytic cells. These data suggest that endogenous
      microbiota promote the crippling immune-suppression characteristic of PDA and
      that the microbiome has potential as a therapeutic target in the modulation of
      disease progression.Significance: We found that a distinct and abundant
      microbiome drives suppressive monocytic cellular differentiation in pancreatic
      cancer via selective Toll-like receptor ligation leading to T-cell anergy.
      Targeting the microbiome protects against oncogenesis, reverses intratumoral
      immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These
      data have implications for understanding immune suppression in pancreatic cancer
      and its reversal in the clinic. Cancer Discov; 8(4); 403-16. (c)2018 AACR.See
      related commentary by Riquelme et al., p. 386This article is highlighted in the
      In This Issue feature, p. 371.

PMID- 29567830
TI  - Cardiac circRNAs arise mainly from constitutive exons rather than alternatively
      spliced exons.
AB  - Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and
      knowledge about their biogenesis and function is still in its infancy. It was
      recently shown that alternative splicing underlies the formation of circular RNAs
      (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which
      circRNAs are formed is still unclear, we hypothesized that alternative splicing,
      and in particular exon skipping, is a major driver of circRNA production. We
      performed RNA sequencing on human and mouse hearts, mapped alternative splicing
      events, and overlaid these with expressed circRNAs at exon-level resolution. In
      addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how
      important Rbm20-mediated alternative splicing is in the production of cardiac
      circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly
      (~90%) produced from constitutive exons and less (~10%) from alternatively
      spliced exons. In Rbm20 KO hearts, we identified 38 differentially expressed
      circRNAs of which 12 were produced from the Ttn gene. Even though Ttn appeared
      the most prominent target of Rbm20 for circularization, we also detected Rbm20
      dependent circRNAs arising from other genes including Fan1, Stk39, Xdh, Bcl2l13,
      and Sorbs1 Interestingly, only Ttn circRNAs seemed to arise from Rbm20-mediated
      skipped exons. In conclusion, cardiac circRNAs are mostly derived from
      constitutive exons, suggesting that these circRNAs are generated at the expense
      of their linear counterpart and that circRNA production impacts the accumulation
      of the linear mRNA.

PMID- 29567832
TI  - Retinol dehydrogenase 11 is essential for the maintenance of retinol homeostasis
      in liver and testis in mice.
AB  - Retinol dehydrogenase 11 (RDH11) is a microsomal short-chain
      dehydrogenase/reductase that recognizes all-trans- and cis-retinoids as
      substrates and prefers NADPH as a cofactor. Previous work has suggested that
      RDH11 contributes to the oxidation of 11-cis-retinol to 11-cis-retinaldehyde
      during the visual cycle in the eye's retinal pigment epithelium. However, the
      role of RDH11 in metabolism of all-trans-retinoids remains obscure. Here, we
      report that microsomes isolated from the testes and livers of Rdh11-/- mice fed a
      regular diet exhibited a 3- and 1.7-fold lower rate of all-trans-retinaldehyde
      conversion to all-trans-retinol, respectively, than the microsomes of WT
      littermates. Testes and livers of Rdh11-/- mice fed a vitamin A-deficient diet
      had ~35% lower levels of all-trans-retinol than those of WT mice. Furthermore,
      the conversion of beta-carotene to retinol via retinaldehyde as an intermediate
      appeared to be impaired in the testes of Rdh11-/-/retinol-binding protein 4-/
      (Rbp4-/-) mice, which lack circulating holo RBP4 and rely on dietary
      supplementation with beta-carotene for maintenance of their retinoid stores.
      Together, these results indicate that in mouse testis and liver, RDH11 functions
      as an all-trans-retinaldehyde reductase essential for the maintenance of
      physiological levels of all-trans-retinol under reduced vitamin A availability.

PMID- 29567833
TI  - Structural basis for the ability of MBD domains to bind methyl-CG and TG sites in
      DNA.
AB  - Cytosine methylation is a well-characterized epigenetic mark and occurs at both
      CG and non-CG sites in DNA. Both methylated CG (mCG)- and mCH (H = A, C, or T)
      containing DNAs, especially mCAC-containing DNAs, are recognized by methyl-CpG
      binding protein 2 (MeCP2) to regulate gene expression in neuron development.
      However, the molecular mechanism involved in the binding of methyl-CpG-binding
      domain (MBD) of MeCP2 to these different DNA motifs is unclear. Here, we
      systematically characterized the DNA-binding selectivities of the MBD domains in
      MeCP2 and MBD1-4 with isothermal titration calorimetry-based binding assays,
      mutagenesis studies, and X-ray crystallography. We found that the MBD domains of
      MeCP2 and MBD1-4 bind mCG-containing DNAs independently of the sequence identity
      outside the mCG dinucleotide. Moreover, some MBD domains bound to both methylated
      and unmethylated CA dinucleotide-containing DNAs, with a preference for the CAC
      sequence motif. We also found that the MBD domains bind to mCA or nonmethylated
      CA DNA by recognizing the complementary TG dinucleotide, which is consistent with
      an overlooked ligand of MeCP2, i.e. the matrix/scaffold attachment regions
      (MARs/SARs) with a consensus sequence of 5'-GGTGT-3' that was identified in early
      1990s. Our results also explain why MeCP2 exhibits similar binding affinity to
      both mCA- and hmCA-containing dsDNAs. In summary, our results suggest that in
      addition to mCG sites, unmethylated CA or TG sites also serve as DNA-binding
      sites for MeCP2 and other MBD-containing proteins. This discovery expands the
      genome-wide activity of MBD-containing proteins in gene regulation.

PMID- 29567834
TI  - The cohesin module is a major determinant of cellulosome mechanical stability.
AB  - Cellulosomes are bacterial protein complexes that bind and efficiently degrade
      lignocellulosic substrates. These are formed by multimodular scaffolding proteins
      known as scaffoldins, which comprise cohesin modules capable of binding dockerin
      bearing enzymes and usually a carbohydrate-binding module that anchors the system
      to a substrate. It has been suggested that cellulosomes bound to the bacterial
      cell surface might be exposed to significant mechanical forces. Accordingly, the
      mechanical properties of these anchored cellulosomes may be important to
      understand and improve cellulosome function. Here we used single-molecule force
      spectroscopy to study the mechanical properties of selected cohesin modules from
      scaffoldins of different cellulosomes. We found that cohesins located in the
      region connecting the cell and the substrate are more robust than those located
      outside these two anchoring points. This observation applies to cohesins from
      primary scaffoldins (i.e. those that directly bind dockerin-bearing enzymes) from
      different cellulosomes despite their sequence differences. Furthermore, we also
      found that cohesin nanomechanics (specifically, mechanostability and the position
      of the mechanical clamp of cohesin) are not significantly affected by other
      cellulosomal components, including linkers between cohesins, multiple cohesin
      repeats, and dockerin binding. Finally, we also found that cohesins (from both
      the connecting and external regions) have poor refolding efficiency but similar
      refolding rates, suggesting that the high mechanostability of connecting cohesins
      may be an evolutionarily conserved trait selected to minimize the occurrence of
      cohesin unfolding, which could irreversibly damage the cellulosome. We conclude
      that cohesin mechanostability is a major determinant of the overall mechanical
      stability of the cellulosome.

PMID- 29567835
TI  - Molecular control of gene expression by Brucella BaaR, an IclR-type
      transcriptional repressor.
AB  - The general stress response sigma factor sigmaE1 directly and indirectly
      regulates the transcription of dozens of genes that influence stress survival and
      host infection in the zoonotic pathogen Brucella abortus Characterizing the
      functions of sigmaE1-regulated genes therefore would contribute to our
      understanding of B. abortus physiology and infection biology. sigmaE1 indirectly
      activates transcription of the IclR family regulator Bab2_0215, but the function
      of this regulator remains undefined. Here, we present a structural and functional
      characterization of Bab2_0215, which we have named B rucella adipic acid
      activated regulator (BaaR). We found that BaaR adopts a classic IclR-family fold
      and directly represses the transcription of two operons with predicted roles in
      carboxylic acid oxidation. BaaR binds two sites on chromosome II between baaR and
      a divergently transcribed hydratase/dehydrogenase (acaD2), and it represses
      transcription of both genes. We identified three carboxylic acids (adipic acid,
      tetradecanedioic acid, and epsilon-aminocaproic acid) and a lactone (epsilon
      caprolactone) that enhance transcription from the baaR and acaD2 promoters.
      However, neither the activating acids nor caprolactone enhanced transcription by
      binding directly to BaaR. Induction of baaR transcription by adipic acid required
      the gene bab2_0213, which encodes a major facilitator superfamily transporter,
      suggesting that Bab2_0213 transports adipic acid across the inner membrane. We
      conclude that a suite of structurally related organic molecules activate
      transcription of genes repressed by BaaR. Our study provides molecular-level
      understanding of a gene expression program in B. abortus that is downstream of
      sigmaE1.

PMID- 29567836
TI  - Histone deacetylase-mediated regulation of endolysosomal pH.
AB  - The pH of the endolysosomal system is tightly regulated by a balance of proton
      pump and leak mechanisms that are critical for storage, recycling, turnover, and
      signaling functions in the cell. Dysregulation of endolysosomal pH has been
      linked to aging, amyloidogenesis, synaptic dysfunction, and various
      neurodegenerative disorders, including Alzheimer's disease. Therefore,
      understanding the mechanisms that regulate luminal pH may be key to identifying
      new targets for managing these disorders. Meta-analysis of yeast microarray
      databases revealed that nutrient-limiting conditions inhibited the histone
      deacetylase (HDAC) Rpd3 and thereby up-regulated transcription of the endosomal
      Na+/H+ exchanger Nhx1, resulting in vacuolar alkalinization. Consistent with
      these findings, Rpd3 inhibition by the HDAC inhibitor and antifungal drug
      trichostatin A induced Nhx1 expression and vacuolar alkalinization.
      Bioinformatics analysis of Drosophila and mouse databases revealed that caloric
      control of the Nhx1 orthologs DmNHE3 and NHE6, respectively, is also mediated by
      HDACs. We show that NHE6 is a target of the transcription factor cAMP-response
      element-binding protein (CREB), a known regulator of cellular responses to low
      nutrient conditions, providing a molecular mechanism for nutrient- and HDAC
      dependent regulation of endosomal pH. Of note, pharmacological targeting of the
      CREB pathway to increase NHE6 expression helped regulate endosomal pH and correct
      defective clearance of amyloid Abeta in an apoE4 astrocyte model of Alzheimer's
      disease. These observations from yeast, fly, mouse, and cell culture models point
      to an evolutionarily conserved mechanism for HDAC-mediated regulation of
      endosomal NHE expression. Our insights offer new therapeutic strategies for
      modulation of endolysosomal pH in fungal infection and human disease.

PMID- 29567837
TI  - The BRD3 ET domain recognizes a short peptide motif through a mechanism that is
      conserved across chromatin remodelers and transcriptional regulators.
AB  - Members of the bromodomain and extra-terminal domain (BET) family of proteins
      (bromodomain-containing (BRD) 2, 3, 4, and T) are widely expressed and highly
      conserved regulators of gene expression in eukaryotes. These proteins have been
      intimately linked to human disease, and more than a dozen clinical trials are
      currently underway to test BET-protein inhibitors as modulators of cancer.
      However, although it is clear that these proteins use their bromodomains to bind
      both histones and transcription factors bearing acetylated lysine residues, the
      molecular mechanisms by which BET family proteins regulate gene expression are
      not well defined. In particular, the functions of the other domains such as the
      ET domain have been less extensively studied. Here, we examine the properties of
      the ET domain of BRD3 as a protein/protein interaction module. Using a
      combination of pulldown and biophysical assays, we demonstrate that BRD3 binds to
      a range of chromatin-remodeling complexes, including the NuRD, BAF, and INO80
      complexes, via a short linear "KIKL" motif in one of the complex subunits. NMR
      based structural analysis revealed that, surprisingly, this mode of interaction
      is shared by the AF9 and ENL transcriptional coregulators that contain an acetyl
      lysine-binding YEATS domain and regulate transcriptional elongation. This
      observation establishes a functional commonality between these two families of
      cancer-related transcriptional regulators. In summary, our data provide insight
      into the mechanisms by which BET family proteins might link chromatin acetylation
      to transcriptional outcomes and uncover an unexpected functional similarity
      between BET and YEATS family proteins.

PMID- 29567838
TI  - Group I chitin deacetylases are essential for higher order organization of chitin
      fibers in beetle cuticle.
AB  - Roles in the organization of the cuticle (exoskeleton) of two chitin deacetylases
      (CDAs) belonging to group I, TcCDA1 and TcCDA2, as well as two alternatively
      spliced forms of the latter, TcCDA2a and TcCDA2b, from the red flour beetle,
      Tribolium castaneum, were examined in different body parts using transmission EM
      and RNAi. Even though all TcCDAs are co-expressed in cuticle-forming cells from
      the hardened forewing (elytron) and ventral abdomen, as well as in the softer
      hindwing and dorsal abdomen, there are significant differences in the tissue
      specificity of expression of the alternatively spliced transcripts. Loss of
      either TcCDA1 or TcCDA2 protein by RNAi causes abnormalities in organization of
      chitinous horizontal laminae and vertical pore canals in all regions of the
      procuticle of both the hard and soft cuticles. Simultaneous RNAi for TcCDA1 and
      TcCDA2 produces the most serious abnormalities. RNAi of either TcCDA2a or TcCDA2b
      affects cuticle integrity to some extent. Following RNAi, there is accumulation
      of smaller disorganized fibers in both the horizontal laminae and pore canals,
      indicating that TcCDAs play a critical role in elongation/organization of smaller
      nanofibers into longer fibers, which is essential for structural integrity of
      both hard/thick and soft/thin cuticles. Immunolocalization of TcCDA1 and TcCDA2
      proteins and effects of RNAi on their accumulation indicate that these two
      proteins function in concert exclusively in the assembly zone in a step involving
      the higher order organization of the procuticle.

PMID- 29567839
TI  - Concurrent drug use among methadone maintenance patients in mountainous areas in
      northern Vietnam.
AB  - OBJECTIVES: With the rise in methadone maintenance therapy (MMT) for drug users
      in Vietnam, there has been growing interest in understanding if and how often MMT
      patients engage in concurrent illicit drug use while on methadone therapy in
      various settings. This study examined factors associated with concurrent opioid
      use among patients on MMT in a mountainous area in Vietnam. SETTING: One urban
      and one rural MMT clinics in Tuyen Quang province. PARTICIPANTS: Survey
      participants consisted of patients who were taking MMT at the selected study
      sites. A convenience sampling approach was used to recruit the participants.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Participants were asked a series of
      questions about their socioeconomic status, current alcohol and tobacco use,
      health problems (measured by the EuroQol-Five Dimension-Five Level instrument),
      psychological distress (measured by Kessler score), and factors associated with
      current and/or previous drug use. Regression models were used to determine
      factors associated with concurrent drug use among MMT patients. RESULTS: Among
      the 241 male MMT patients included in the study, 13.4% reported concurrent opioid
      use. On average, the longer patients had been enrolled in MMT, the less likely
      they were to concurrently use drugs. Conversely, patients with higher levels of
      psychological distress were more likely to engage in concurrent drug use while on
      MMT. CONCLUSION: Longer duration of MMT was significantly correlated with reduced
      illicit drug use among participants. Higher levels of psychological distress were
      associated with increased use of illicit drugs among MMT patients. Regardless of
      distance, long-term MMT is still effective and should be expanded in mountainous
      areas.

PMID- 29567840
TI  - Motivation and main flavour of use, use with nicotine and dual use of electronic
      cigarettes in Barcelona, Spain: a cross-sectional study.
AB  - OBJECTIVE: This study seeks to describe current e-cigarette users' patterns of
      use including primary motivation for use, dual use, use with nicotine and
      principal flavour used, according to individuals' sociodemographic
      characteristics and conventional tobacco consumption in Barcelona, Spain. DESIGN,
      SETTING AND PARTICIPANTS: This is a cross-sectional study of adult (>=18) current
      e-cigarette users of Barcelona (n=600), recruited in 2015. Researchers calculated
      percentages and ORs with their 95% CIs of users' e-cigarette use with nicotine,
      primary motivation for use and preferred flavour. The analyses were stratified by
      sociodemographic variables including sex, age and level of education and by
      patterns of e-cigarette use and past and current conventional tobacco use.
      RESULTS: The most prevalent motivation for using e-cigarettes was to reduce
      tobacco smoking (48%, n=288), followed by quitting smoking (39.2%, n=235), and to
      use e-cigarettes in places where tobacco smoking was prohibited (10.2%, n=61).
      The most prevalent primary flavour used was tobacco (49%, n=294), followed by
      fruit (19.5%, n=117). People younger than 25 years old (OR=4.36, 95% CI 1.99 to
      9.57) were more likely than older people to use them where smoking cigarettes was
      prohibited. A greater proportion of those in the youngest age group preferred
      fruit flavour compared with older individuals (29.3%, n=41). CONCLUSIONS: Younger
      users of e-cigarettes and non-smokers are more likely to use flavours other than
      tobacco and to use e-cigarettes mainly for recreational purposes.

PMID- 29567841
TI  - Association of socioeconomic status with financial burden of disease among
      elderly patients with cardiovascular disease: evidence from the China Health and
      Retirement Longitudinal Survey.
AB  - OBJECTIVES: The prevalence of cardiovascular diseases (CVD) within low-income and
      middle-income countries has reached epidemic proportions. However, the
      association between out-of-pocket (OOP) payment and socioeconomic status (SES) of
      patients with CVD is not well studied. We aimed to understand the financial
      burden among Chinese middle-aged and older patients with CVD, and whether there
      was an association with SES. SETTINGS: A nationally representative survey-The
      China Health and Retirement Longitudinal Survey (CHARLS)-was conducted in 28
      provinces of mainland China in 2011 and 2013. PARTICIPANTS: Of the over 18 000
      CHARLS respondents, eligible participants were those aged 45 years and over who
      had been previously diagnosed with CVD. OUTCOME MEASURES: Financial burden was
      measured by individual OOP payment and household catastrophic health expenditure
      (CHE) occurrence (ie, the annual household health expenditure was 40% or more of
      the total non-food household expenditure). Multilevel regression models were used
      to explore the association between financial burden and SES. RESULTS: Among
      CHARLS respondents, CVD prevalence increased from 14.7% in 2011 to 16.6% in 2013.
      Average annual CVD OOP payment increased from 5000 RMB (770 USD) to 6120 RMB (970
      USD). Furthermore, CHE occurrence increased from 44.2% to 48.1%. Patients spent
      almost twice on outpatient as on inpatient services. Two of the three SES
      indicators (total household expenditure, occupation type) were found to be
      associated with CVD OOP payment amount, and the likelihood of CHE. Unemployed
      patients had a higher likelihood of CHE compared with agricultural workers. Rural
      urban difference was associated with the likelihood of CHE in 2011 alone.
      CONCLUSION: The Chinese health system should use this health expenditure pattern
      among patients with CVD to create more equitable health insurance schemes that
      financially balance between outpatient and inpatient care, and provide better
      financial risk protection to patients with low SES.

PMID- 29567842
TI  - Prevalence of potentially inappropriate prescribing in a subpopulation of older
      European clinical trial participants: a cross-sectional study.
AB  - OBJECTIVES: To estimate and compare the prevalence and type of potentially
      inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) among
      community-dwelling older adults (>=65 years) enrolled to a clinical trial in
      three European countries. DESIGN: A secondary analysis of the Thyroid Hormone
      Replacement for Subclinical Hypothyroidism Trial dataset. PARTICIPANTS: A subset
      of 48/80 PIP and 22/34 PPOs indicators from the Screening Tool of Older Persons
      Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) V2
      criteria were applied to prescribed medication data for 532/737 trial
      participants in Ireland, Switzerland and the Netherlands. RESULTS: The overall
      prevalence of PIP was lower in the Irish participants (8.7%) compared with the
      Swiss (16.7%) and Dutch (12.5%) participants (P=0.15) and was not statistically
      significant. The overall prevalence of PPOs was approximately one-quarter in the
      Swiss (25.3%) and Dutch (24%) participants and lower in the Irish (14%)
      participants (P=0.04) and the difference was statistically significant. The
      hypnotic Z-drugs were the most frequent PIP in Irish participants, (3.5%, n=4),
      while it was non-steroidal anti-inflammatory drug and oral anticoagulant
      combination, sulfonylureas with a long duration of action, and benzodiazepines
      (all 4.3%, n=7) in Swiss, and benzodiazepines (7.1%, n=18) in Dutch participants.
      The most frequent PPOs in Irish participants were vitamin D and calcium in
      osteoporosis (3.5%, n=4). In the Swiss and Dutch participants, they were bone
      antiresorptive/anabolic therapy in osteoporosis (9.9%, n=16, 8.6%, n=22)
      respectively. The odds of any PIP after adjusting for age, sex, multimorbidity
      and polypharmacy were (adjusted OR (aOR)) 3.04 (95% CI 1.33 to 6.95, P<0.01) for
      Swiss participants and aOR 1.74 (95% CI 0.79 to 3.85, P=0.17) for Dutch
      participants compared with Irish participants. The odds of any PPOs were aOR 2.48
      (95% CI 1.27 to 4.85, P<0.01) for Swiss participants and aOR 2.10 (95% CI 1.11 to
      3.96, P=0.02) for Dutch participants compared with Irish participants.
      CONCLUSIONS: This study has estimated and compared the prevalence and type of PIP
      and PPOs among this cohort of community-dwelling older people. It demonstrated a
      significant difference in the prevalence of PPOs between the three populations.
      Further research is urgently needed into the impact of system level factors as
      this has important implications for patient safety, healthcare provision and
      economic costs.

PMID- 29567843
TI  - A novel inpatient complex pain team: protocol for a mixed-methods evaluation of a
      single-centre pilot study.
AB  - INTRODUCTION: Complex pain is a debilitating condition that is responsible for
      low quality of life and significant economic impacts. Although best practice in
      the treatment of complex pain employs a multidisciplinary team, many patients do
      not have access to this care, leading to poor outcomes. METHODS AND ANALYSIS:
      This study evaluates a novel inpatient complex pain team at a large London
      teaching hospital. A multidisciplinary pain team comprising specialist doctors,
      nurses, psychologists and physiotherapists was instituted for inpatients with
      complex pain who will undergo an intense and bespoke evidence-based programme
      which will then be integrated into the community. A mixed-methods evaluation will
      take place and patients will be recruited over the course of 1 year. A
      qualitative arm will interview 15 staff and 15 patients on recruitment and again
      6 months later looking to compare and contrast the new pain team with past
      experiences of pain management. A quantitative arm will assess clinical outcomes
      using validated scoring tools. An economic evaluation will seek to evaluate the
      relative cost of the service by comparing healthcare costs before and after the
      intervention. ETHICS AND DISSEMINATION: The study was categorised as a service
      evaluation, so formal ethical approval was not considered necessary. Participant
      recruitment began in January 2016 and the 1-year follow-up will end in November
      2017. The results of this study will be published in 2018.

PMID- 29567844
TI  - Seroprevalence of antibodies against varicella zoster virus and rubella virus
      among newly recruited expatriate healthcare workers: a cross-sectional study.
AB  - OBJECTIVES: To assess the state of immunity to varicella zoster virus (VZV) and
      rubella virus (RV) among newly recruited healthcare workers (HCWs) in Kuwait
      before they begin work, and to determine whether there are differences in the
      prevalence of seronegativity according to nationality, gender, age group and
      occupation group. SETTING: This cross-sectional study involved analysis of blood
      samples from workers newly recruited to the Kuwaiti healthcare system.
      PARTICIPANTS: All new non- national HCWs recruited during the study period
      (n=1540). INTERVENTION: Enzyme-linked immunoassays for VZV-specific and RV
      specific IgG were performed. RESULTS: Among HCWs, 81.9% and 93.5% were immune to
      VZV and RV, respectively. Male seronegativity was higher than that of females for
      both viruses. Regarding VZV, the majority of seronegative individuals were
      Indians (23.5%), followed by Somalis (12.5), Filipinos (6.5) and Egyptians
      (5.4%); the between-group differences were significant for all groups. The age
      groups 20-30 and 30-40 years were most likely to be seronegative, with
      prevalences of 18.2% and 18.9%, respectively. VZV seronegativity was most common
      among nurses (21.1%) and least common among physicians (9.2%), and the difference
      was significant. In addition, RV seronegativity was most frequent among Somalis
      (12.5%) and lowest among Indians (5.3%); other nationalities (Egyptian, Filipino
      and others) ranged between 9.1% and 9.6%. Seronegative individuals were most
      frequently in the younger age group (<20 years old) (17.5%), followed by the >40
      years old group (10.4%). RV seronegativity was highest among nurses (6.9%) and
      lowest among physicians (5.2%). CONCLUSION: The prevalence of seronegativity is
      highest among Indians for VZV and Somalis for RV, and HCWs aged 20-40 years for
      VZV and <20 years for RV. For both viruses, the seronegativity rate was highest
      for male HCWs, and for nurses compared with other HCWs, with physicians having
      the lowest prevalence of both viruses.

PMID- 29567846
TI  - Can a midwife-led continuity model improve maternal services in a low-resource
      setting? A non-randomised cluster intervention study in Palestine.
AB  - OBJECTIVES: To improve maternal health services in rural areas, the Palestinian
      Ministry of Health launched a midwife-led continuity model in the West Bank in
      2013. Midwives were deployed weekly from governmental hospitals to provide
      antenatal and postnatal care in rural clinics. We studied the intervention's
      impact on use and quality indicators of maternal services after 2 years'
      experience. DESIGN: A non-randomised intervention design was chosen. The study
      was based on registry data only available at cluster level, 2 years before
      (2011and2012) and 2 years after (2014and2015) the intervention. SETTING: All 53
      primary healthcare clinics in Nablus and Jericho regions were stratified for
      inclusion. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was number of
      antenatal visits. Important secondary outcomes were number of referrals to
      specialist care and number of postnatal home visits. Differences in changes
      within the two groups before and after the intervention were compared by using
      mixed effect models. RESULTS: 14 intervention clinics and 25 control clinics were
      included. Number of antenatal visits increased by 1.16 per woman in the
      intervention clinics, while declined by 0.39 in the control clinics, giving a
      statistically significant difference in change of 1.55 visits (95% CI 0.90 to
      2.21). A statistically significant difference in number of referrals was observed
      between the groups, giving a ratio of rate ratios of 3.65 (2.78-4.78) as number
      of referrals increased by a rate ratio of 3.87 in the intervention group, while
      in the control the rate ratio was only 1.06.Home visits increased substantially
      in the intervention group but decreased in the control group, giving a ratio of
      RR 97.65 (45.20 - 210.96) CONCLUSION: The Palestinian midwife-led continuity
      model improved use and some quality indicators of maternal services. More
      research should be done to investigate if the model influenced individual health
      outcomes and satisfaction with care. TRIAL REGISTRATION NUMBER: NCT03145571;
      Results.

PMID- 29567845
TI  - Association of dispositional optimism with Life's Simple 7's Cardiovascular
      Health Index: results from the Hispanic Community Health Study/Study of Latinos
      (HCHS/SOL) Sociocultural Ancillary Study (SCAS).
AB  - OBJECTIVES: Mounting evidence links positive psychological functioning to
      restorative health processes and favourable medical outcomes. However, very
      little is known about the relationship between optimism, an indicator of
      psychological functioning and the American Heart Association (AHA)-defined
      concept of cardiovascular health (CVH), particularly in Hispanics/Latinos of
      diverse backgrounds. To address limitations of existing literature, this study
      investigated the association between dispositional optimism and CVH in a
      heterogeneous sample of Hispanics/Latinos residing in the USA. DESIGN: Cross
      sectional study. PARTICIPANTS AND SETTING: Data were analysed from 4919 adults
      ages 18-75 of the Hispanic Community Health Study/Study of Latinos parent study
      and the Sociocultural Ancillary Study. MAIN OUTCOME MEASURES: Optimism was
      assessed using the 6-item Life Orientation Test-Revised (range from 6 to 30). AHA
      classification standards were used to derive an additive CVH score with
      operationalisation of indicators as Ideal, Intermediate and Poor. The overall CVH
      score included indicators of diet, body mass index, physical activity,
      cholesterol, blood pressure, fasting glucose and smoking status. Multivariate
      linear and logistic regressions were used to examine associations of optimism
      with CVH (Life's Simple 7), after adjusting for sociodemographic factors and
      depressive symptoms. RESULTS: Each increase in the optimism total score was
      associated with a greater CVH score (beta=0.03 per unit increase, 95% CI 0.01 to
      0.05). When modelling tertiles of optimism, participants with moderate (beta=0.24
      to 95% CI 0.06 to 0.42) and high (beta=0.12, 95% CI 0.01 to 0.24) levels of
      optimism displayed greater CVH scores when compared with their least optimistic
      peers. CONCLUSION: This study offers preliminary evidence for an association
      between optimism and CVH in a large heterogeneous group of Hispanic/Latino
      adults. Our study adds scientific knowledge of psychological assets that may
      promote CVH and suggests a novel therapeutic target for consideration. Future
      studies are needed to explore causality and potential mechanism underlying the
      relationship between positive emotion and heart health.

PMID- 29567847
TI  - Reliability of coded data to identify earliest indications of cognitive decline,
      cognitive evaluation and Alzheimer's disease diagnosis: a pilot study in England.
AB  - OBJECTIVES: Evaluate the reliability of using diagnosis codes and prescription
      data to identify the timing of symptomatic onset, cognitive assessment and
      diagnosis of Alzheimer's disease (AD) among patients diagnosed with AD. METHODS:
      This was a retrospective cohort study using the UK Clinical Practice Research
      Datalink (CPRD). The study cohort consisted of a random sample of 50 patients
      with first AD diagnosis in 2010-2013. Additionally, patients were required to
      have a valid text-field code and a hospital episode or a referral in the 3 years
      before the first AD diagnosis. The earliest indications of cognitive impairment,
      cognitive assessment and AD diagnosis were identified using two approaches: (1)
      using an algorithm based on diagnostic codes and prescription drug information
      and (2) using information compiled from manual review of both text-based and
      coded data. The reliability of the code-based algorithm for identifying the
      earliest dates of the three measures described earlier was evaluated relative to
      the comprehensive second approach. Additionally, common cognitive assessments
      (with and without results) were described for both approaches. RESULTS: The two
      approaches identified the same first dates of cognitive symptoms in 33 (66%) of
      the 50 patients, first cognitive assessment in 29 (58%) patients and first AD
      diagnosis in 43 (86%) patients. Allowing for the dates from the two approaches to
      be within 30 days, the code-based algorithm's success rates increased to 74%, 70%
      and 94%, respectively. Mini-Mental State Examination was the most commonly
      observed cognitive assessment in both approaches; however, of the 53 tests
      performed, only 19 results were observed in the coded data. CONCLUSIONS: The code
      based algorithm shows promise for identifying the first AD diagnosis. However,
      the reliability of using coded data to identify earliest indications of cognitive
      impairment and cognitive assessments is questionable. Additionally, CPRD is not a
      recommended data source to identify results of cognitive assessments.

PMID- 29567848
TI  - Self-management interventions for adults with chronic kidney disease: a scoping
      review.
AB  - OBJECTIVE: To systematically identify and describe self-management interventions
      for adult patients with chronic kidney disease (CKD). SETTING: Community-based.
      PARTICIPANTS: Adults with CKD stages 1-5 (not requiring kidney replacement
      therapy). INTERVENTIONS: Self-management strategies for adults with CKD. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Using a scoping review, electronic databases and
      grey literature were searched in October 2016 to identify self-management
      interventions for adults with CKD stages 1-5 (not requiring kidney replacement
      therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed
      method studies were included and study selection and data extraction were
      independently performed by two reviewers. Outcomes included behaviours,
      cognitions, physiological measures, symptoms, health status and healthcare.
      RESULTS: Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre
      post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions
      were included. The most common intervention topic was diet/nutrition and
      interventions were regularly delivered face to face. Interventions were
      administered by a variety of providers, with nursing professionals the most
      common health professional group. Cognitions (ie, changes in general CKD
      knowledge, perceived self-management and motivation) were the most frequently
      reported outcome domain that showed improvement. Less than 1% of the
      interventions were co-developed with patients and 20% were based on a theory or
      framework. CONCLUSIONS: There was a wide range of self-management interventions
      with considerable variability in outcomes for adults with CKD. Major gaps in the
      literature include lack of patient engagement in the design of the interventions,
      with the majority of interventions not applying a behavioural change theory to
      inform their development. This work highlights the need to involve patients to co
      developed and evaluate a self-management intervention based on sound theories and
      clinical evidence.

PMID- 29567849
TI  - Diagnostic accuracy of self-administered urine glucose test strips as a diabetes
      screening tool in a low-resource setting in Cambodia.
AB  - OBJECTIVE: Screening for diabetes in low-resource countries is a growing
      challenge, necessitating tests that are resource and context appropriate. The aim
      of this study was to determine the diagnostic accuracy of a self-administered
      urine glucose test strip compared with alternative diabetes screening tools in a
      low-resource setting of Cambodia. DESIGN: Prospective cross-sectional study.
      SETTING: Members of the Borey Santepheap Community in Cambodia (Phnom Penh
      Municipality, District Dangkao, Commune Chom Chao). PARTICIPANTS: All households
      on randomly selected streets were invited to participate, and adults at least 18
      years of age living in the study area were eligible for inclusion. OUTCOMES: The
      accuracy of self-administered urine glucose test strip positivity, Hemoglobin A1c
      (HbA1c)>6.5% and capillary fasting blood glucose (cFBG) measurement >=126 mg/dL
      were assessed against a composite reference standard of cFBGmeasurement >=200
      mg/dL or venous blood glucose 2 hours after oral glucose tolerance test (OGTT)
      >=200 mg/dL. RESULTS: Of the 1289 participants, 234 (18%) had diabetes based on
      either cFBG measurement (74, 32%) or the OGTT (160, 68%). The urine glucose test
      strip was 14% sensitive and 99% specific and failed to identify 201 individuals
      with diabetes while falsely identifying 7 without diabetes. Those missed by the
      urine glucose test strip had lower venous fasting blood glucose, lower venous
      blood glucose 2 hours after OGTT and lower HbA1c compared with those correctly
      diagnosed. CONCLUSIONS: Low cost, easy to use diabetes tools are essential for
      low-resource communities with minimal infrastructure. While the urine glucose
      test strip may identify persons with diabetes that might otherwise go undiagnosed
      in these settings, its poor sensitivity cannot be ignored. The massive burden of
      diabetes in low-resource settings demands improvements in test technologies.

PMID- 29567851
TI  - Role of CHA2DS2-VASc score in predicting new-onset atrial fibrillation in
      patients with type 2 diabetes mellitus with and without hyperosmolar
      hyperglycaemic state: real-world data from a nationwide cohort.
AB  - PURPOSE: The objective of the current study was to explore the role of CHA2DS2
      VASc score in predicting incidence of atrial fibrillation (AF) in patients with
      type 2 diabetes mellitus (DM). Furthermore, the use of the CHA2DS2-VASc score for
      stratifying new-onset AF risk in patients with DM and with/without hyperosmolar
      hyperglycaemic state (HHS) was also compared. METHODS: The study subjects were
      identified from Longitudinal Health Insurance Database provided by the National
      Health Research Institutes. The patients with DM were divided into two groups
      based on a history of HHS or not. The predictive ability of CHA2DS2-VASc score
      for stratifying new-onset AF risk in the two groups was calculated using the area
      under the curve of receiver-operating characteristic (AUROC). RESULTS: The
      present study involved a total of 69 530 patients with type 2 DM. Among them,
      1558 patients had a history of HHS, whereas 67 972 patients did not. The AUROC of
      the CHA2DS2-VASc score as a predictor of incident AF in patients with DM and
      with/without HHS was 0.67 (95% CI 0.59 to 0.75) and 0.71 (95% CI 0.70 to 0.72),
      respectively. CONCLUSIONS: To conclude, we reported for the first time on the
      assessment of CHA2DS2-VASc score for incident AF risk discrimination in patients
      with type 2 DM. We further found that the predictive ability of the CHA2DS2-VASc
      score was attenuated in patients with type 2 DM and with HHS in comparison with
      those without HHS.

PMID- 29567850
TI  - Levels of detection of hypertension in primary medical care and interventions to
      improve detection: a systematic review of the evidence since 2000.
AB  - OBJECTIVES: In England, many hypertensives are not detected by primary medical
      care. Higher detection is associated with lower premature mortality. We aimed to
      summarise recent evidence on detection and interventions to improve detection in
      order to inform policies to improve care. DESIGN: Data sources: systematic review
      of articles published since 2000. Searches of Medline and Embase were undertaken.
      Eligibility criteria: published in English, any study design, the setting was
      general practice and studies included patients aged 18 or over. EXCLUSION
      CRITERIA: screening schemes, studies in primary care settings other than general
      practice, discussion or comment pieces. PARTICIPANTS: adult patients of primary
      medical care services. SYNTHESIS: study heterogeneity precluded a statistical
      synthesis, and papers were described in summary tables. RESULTS: Seventeen
      quantitative and one qualitative studies were included. Detection rates varied by
      gender and ethnic group, but longitudinal studies indicated an improvement in
      detection over time. Patient socioeconomic factors did not influence detection,
      but living alone was associated with lower detection. Few health system factors
      were associated with detection, but in two studies higher numbers of general
      practitioners per 1000 population were associated with higher detection. Three
      studies investigated interventions to improve detection, but none showed evidence
      of effectiveness. LIMITATIONS: The search was limited to studies published from
      2000, in English. There were few studies of interventions to improve detection,
      and a meta-analysis was not possible. CONCLUSIONS AND IMPLICATIONS: Levels of
      detection of hypertension by general practices may be improving, but large
      numbers of people with hypertension remain undetected. Improvement in detection
      is therefore required, but guidance for primary medical care is not provided by
      the few studies of interventions included in this review. Primary care teams
      should continue to use low-cost, practical approaches to detecting hypertension
      until evidence from new studies of interventions to improve detection is
      available.

PMID- 29567852
TI  - Effects of supplementation with carnosine and other histidine-containing
      dipeptides on chronic disease risk factors and outcomes: protocol for a
      systematic review of randomised controlled trials.
AB  - INTRODUCTION: Ageing of populations globally, coupled with the obesity epidemic,
      has resulted in the rising prevalence of chronic diseases including diabetes,
      cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of
      risk factors that contribute to these diseases is key in managing the global
      burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide
      with anti-inflammatory, antioxidative and antiglycating properties may have a
      role in the prevention of chronic diseases; however, no previous reviews have
      examined the effects of carnosine and other histidine-containing peptides (HCDs)
      on chronic disease risk factors and outcomes. We aim to conduct a comprehensive
      systematic review to examine the effects of supplementation with carnosine and
      other HCDs on chronic disease risk factors and outcomes and to identify relevant
      knowledge gaps. METHODS AND ANALYSIS: Electronic databases including Medline,
      Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based
      Medicine will be systematically searched to identify randomised controlled trials
      (RCTs) and systematic reviews of RCTs, comparing supplementation with carnosine
      and/or other HCDs versus placebo, usual care or other pharmacological or non
      pharmacological interventions. One reviewer will screen titles and abstracts for
      eligibility according to prespecified inclusion criteria, after which two
      independent reviewers will perform data extraction and quality appraisal. Meta
      analyses, metaregression and subgroup analyses will be conducted where
      appropriate. ETHICS AND DISSEMINATION: Ethics approval is not required as this
      review does not involve primary data collection. This review will generate level
      one evidence regarding the effects of carnosine supplementation on chronic
      disease risk factors and outcomes and will be disseminated through peer-reviewed
      publications and at conference meetings to inform future research on the efficacy
      of carnosine supplementation for the prevention of chronic diseases. PROSPERO
      REGISTRATION NUMBER: CRD42017075354.

PMID- 29567853
TI  - Roles played by community cadres to support retention in PMTCT Option B+ in four
      African countries: a qualitative rapid appraisal.
AB  - OBJECTIVES: To explore the roles of community cadres in improving access to and
      retention in care for PMTCT (prevent mother-to-child transmission of HIV)
      services in the context of PMTCT Option B+ treatment scale-up in high burden low
      income and lower-middle income countries. DESIGN/METHODS: Qualitative rapid
      appraisal study design using semistructured in-depth interviews and focus group
      discussions (FGDs) between 8 June and 31 July 2015. SETTING AND PARTICIPANTS:
      Interviews were conducted in the offices of Ministry of Health Staff,
      Implementing partners, district offices and health facility sites across four low
      income and lower-middle income countries: Cote D'Ivoire, Democratic Republic of
      Congo (DRC), Malawi and Uganda. A range of individual interviews and FGDs with
      key stakeholders including Ministry of Health employees, Implementation partners,
      district management teams, facility-based health workers and community cadres. A
      total number of 18, 28, 31 and 83 individual interviews were conducted in Malawi,
      Cote d'Ivoire, DRC and Uganda, respectively. A total number of 15, 9, 10 and 16
      mixed gender FGDs were undertaken in Malawi, Cote d'Ivoire, DRC and Uganda,
      respectively. RESULTS: Community cadres either operated solely in the community,
      worked from health centres or in combination and their mandates were PMTCT
      specific or included general HIV support and other health issues. Community
      cadres included volunteers, those supported by implementing partners or employed
      directly by the Ministry of Health. Their complimentary roles along the continuum
      of HIV care and treatment include demand creation, household mapping of pregnant
      and lactating women, linkage to care, infant follow-up and adherence and
      retention support. CONCLUSIONS: Community cadres provide an integral link between
      communities and health facilities, supporting overstretched health workers in HIV
      client support and follow-up. However, their role in health systems is neither
      standardised nor systematic and there is an urgent need to invest in the
      standardisation of and support to community cadres to maximise potential health
      impacts.

PMID- 29567855
TI  - Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress
      granules through their deubiquitylating activities.
AB  - Stress granules are transient cytoplasmic foci induced by various stresses that
      contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to
      modulate mRNA translation and stress responses. Here, we show that the
      deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules.
      Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains.
      Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and
      accelerated assembly of heat-induced stress granules, suggesting that these
      enzymes regulate the stability of the stress granules through their ubiquitin
      isopeptidase activity. Moreover, disassembly of heat-induced stress granules
      after returning the cells to normal temperatures was markedly repressed by
      individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin
      mutant lacking the C-terminal diglycine motif caused the accumulation of
      unanchored ubiquitin chains and the repression of the disassembly of heat-induced
      stress granules. As unanchored ubiquitin chains are preferred substrates for
      USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced
      stress granules by mediating the hydrolysis of unanchored ubiquitin chains while
      USP13 regulates stress granules through deubiquitylating protein-conjugated
      ubiquitin chains.This article has an associated First Person interview with the
      first author of the paper.

PMID- 29567854
TI  - Risk factors of asthma exacerbation based on asthma severity: a nationwide
      population-based observational study in South Korea.
AB  - OBJECTIVES: Asthma exacerbation, associated with many risks factors, can reflect
      management failure. However, little is known about how risk factors are
      associated with exacerbation, according to asthma severity. We aimed to
      investigate differences in risk factors in patients with different asthma
      severity and evaluate whether risk factors differed between frequent exacerbators
      and patients with single exacerbation. DESIGN: Nationwide population-based
      observational study. SETTING: Korean National Sample Cohort database.
      PARTICIPANTS: We included 22 130 adults with asthma diagnoses more than twice
      (ICD-10 (International Classification of Diseases, Tenth revision) codes J45 and
      J46) and one prescription for asthma medication from 2010 to 2011. OUTCOME
      MEASURES: Asthma exacerbation was defined as having a corticosteroid (CS) burst
      characterised by a prescription of high-dose oral CS for >=3 days or one systemic
      CS injection, hospitalisation or emergency department visit. RESULTS: Among
      severities, history of CS bursts was significantly associated with exacerbation.
      In mild and moderate asthma, exacerbation was significantly associated with age
      >=45 years, being female, gastro-oesophageal reflux disease and chronic rhinitis.
      High medication possession ratio (MPR>=50%), compared with low MPR (<20%) showed
      adjusted ORs of 0.828 (95% CI 0.707 to 0.971) and 0.362 (0.185 to 0.708) in
      moderate and severe asthma, respectively. In severe asthma, compared with mild
      asthma, only allergic rhinitis and history of hospitalisation were strongly
      associated with exacerbation. When comparing frequent exacerbators to patients
      with single exacerbation, age >=45 years, atopic dermatitis, anxiety and history
      of CS burst were significant risk factors in mild and moderate asthma, whereas no
      risk factors were significant in severe asthma. CONCLUSIONS: Different
      associations between risk factors and asthma exacerbations based on asthma
      severity suggest that patients with mild asthma require greater attention to
      their age and comorbidities, whereas those with severe asthma require greater
      attention to hospitalisation history and drug adherence.

PMID- 29567856
TI  - Genetic dissection of the phosphoinositide cycle in Drosophila photoreceptors.
AB  - Phototransduction in Drosophila is mediated by phospholipase C-dependent
      hydrolysis of PIP2-, and is an important model for phosphoinositide signalling.
      Although generally assumed to operate by generic machinery conserved from yeast
      to mammals, some key elements of the phosphoinositide cycle have yet to be
      identified in Drosophila photoreceptors. Here, we used transgenic flies
      expressing fluorescently tagged probes (P4M and TbR332H), which allow in vivo
      quantitative measurements of PI4P and PIP2 dynamics in photoreceptors of intact
      living flies. Using mutants and RNA interference for candidate genes potentially
      involved in phosphoinositide turnover, we identified Drosophila PI4KIIIalpha
      (CG10260) as the PI4-kinase responsible for PI4P synthesis in the photoreceptor
      membrane. Our results also indicate that PI4KIIIalpha activity requires rbo (the
      Drosophila orthologue of Efr3) and CG8325 (orthologue of YPP1), both of which are
      implicated as scaffolding proteins necessary for PI4KIIIalpha activity in yeast
      and mammals. However, our evidence indicates that the recently reported central
      role of dPIP5K59B (CG3682) in PIP2 synthesis in the rhabdomeres should be re
      evaluated; although PIP2 resynthesis was suppressed by RNAi directed against
      dPIP5K59B, little or no defect was detected in a reportedly null mutant (dPIP5K18
      ).

PMID- 29567857
TI  - Targeting Brain-Adaptive Cancer Stem Cells Prohibits Brain Metastatic
      Colonization of Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) exhibits more traits possessed by cancer
      stem cells (CSC) than other breast cancer subtypes and is more likely to develop
      brain metastases. TNBC patients usually have shorter survival time after
      diagnosis of brain metastasis, suggesting an innate ability of TNBC tumor cells
      in adapting to the brain. In this study, we establish novel animal models to
      investigate early tumor adaptation in brain metastases by introducing both
      patient-derived and cell line-derived CSC-enriched brain metastasis tumorsphere
      cells into mice. We discovered astrocyte-involved tumor activation of
      protocadherin 7 (PCDH7)-PLCbeta-Ca2+-CaMKII/S100A4 signaling as a mediator of
      brain metastatic tumor outgrowth. We further identified and evaluated the
      efficacy of a known drug, the selective PLC inhibitor edelfosine, in suppressing
      the PCDH7 signaling pathway to prohibit brain metastases in the animal models.
      The results of this study reveal a novel signaling pathway for brain metastases
      in TNBC and indicate a promising strategy of metastatic breast cancer prevention
      and treatment by targeting organ-adaptive cancer stem cells.Significance: These
      findings identify a compound to block adaptive signaling between cancer stem
      cells and brain astrocytes. Cancer Res; 78(8); 2052-64. (c)2018 AACR.

PMID- 29567859
TI  - Urgent: Stop Preventable Infections Now.

PMID- 29567858
TI  - Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults.
AB  - BACKGROUND AND OBJECTIVES: Cognitive function worsens as kidney function
      declines, but mechanisms contributing to this association are not completely
      understood. Metabolic acidosis, a common complication of CKD, leads to neural
      networks overexcitation and is involved in cerebral autoregulation. We aimed to
      evaluate the association between serum bicarbonate concentration as a measure of
      metabolic acidosis, and cognitive function in hypertensive adults with and
      without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five cognitive
      summary scores were measured (global cognitive function, executive function,
      memory, attention/concentration, and language) in 2853 participants in the
      Systolic BP Intervention Trial (SPRINT). Multivariable linear regression models
      adjusted for demographics, comorbidities, systolic BP, medications, eGFR and
      albuminuria evaluated the cross-sectional association between bicarbonate and
      cognition at SPRINT baseline. In a subset (n=681) who underwent brain magnetic
      resonance imaging, the models were adjusted for white matter hyperintensity
      volume, vascular reactivity, and cerebral blood flow. RESULTS: The mean age (SD)
      was 68 (8.5) years. Global cognitive and executive functions were positively
      associated with serum bicarbonate (estimate [SEM]: 0.014 [0.006]; P=0.01, and
      0.018 [0.006]; P=0.003, respectively). Each 1 mEq/L lower bicarbonate level had a
      similar association with global cognitive and executive function as being 4.3 and
      5.4 months older, respectively. The association with global cognition persisted
      after magnetic resonance imaging findings adjustment (estimate [SEM]: 0.03
      [0.01]; P=0.01). There was no association between serum bicarbonate level and
      memory, attention/concentration, and language. CONCLUSIONS: In a large cohort of
      hypertensive adults, higher serum bicarbonate levels were independently
      associated with better global cognitive and executive performance.
      (ClinicalTrials.gov: NCT01206062).

PMID- 29567860
TI  - The Role of Bicarbonate in Cognition: Acidosis May Be Corrosive to the Brain.

PMID- 29567861
TI  - What We Learned from Ebola: Preparing Dialysis Units for the Next Outbreak.

PMID- 29567862
TI  - Addressing the Problem of Multidrug-Resistant Organisms in Dialysis.

PMID- 29567863
TI  - 100% Use of Infection Control Procedures in Hemodialysis Facilities: Call to
      Action.

PMID- 29567864
TI  - Systems Thinking and Leadership: How Nephrologists Can Transform Dialysis Safety
      to Prevent Infections.
AB  - Infections are the second leading cause of death for patients with ESKD. Despite
      multiple efforts, nephrologists have been unable to prevent infections in
      dialysis facilities. The American Society of Nephrology and the Centers for
      Disease Control and Prevention have partnered to create Nephrologists
      Transforming Dialysis Safety to promote nephrologist leadership and engagement in
      efforts to "Target Zero" preventable dialysis infections. Because traditional
      approaches to infection control and prevention in dialysis facilities have had
      limited success, Nephrologists Transforming Dialysis Safety is reconceptualizing
      the problem in the context of the complexity of health care systems and
      organizational behavior. By identifying different parts of a problem and
      attempting to understand how these parts interact and produce a result, systems
      thinking has effectively tackled difficult problems in dynamic settings. The
      dialysis facility is composed of different physical and human elements that are
      interconnected and affect not only behavior but also, the existence of a culture
      of safety that promotes infection prevention. Because dialysis infections result
      from a complex system of interactions between caregivers, patients, dialysis
      organizations, and the environment, attempts to address infections by focusing on
      one element in isolation often fail. Creating a sense of urgency and commitment
      to eradicating dialysis infections requires leadership and motivational skills.
      These skills are not taught in the standard nephrology or medical director
      curriculum. Effective leadership by medical directors and engagement in infection
      prevention by nephrologists are required to create a culture of safety. It is
      imperative that nephrologists commit to leadership training and embrace their
      potential as change agents to prevent infections in dialysis facilities. This
      paper explores the systemic factors contributing to the ongoing dialysis
      infection crisis in the United States and the role of nephrologists in instilling
      a culture of safety in which infections can be anticipated and prevented.

PMID- 29567865
TI  - Indomethacin Enhances Brown Fat Activity.
AB  - Indomethacin, a nonsteroidal anti-inflammatory drug, has been shown to induce
      white adipocyte differentiation; however, its roles in brown adipocyte
      differentiation and activation in brown adipose tissue (BAT) and obesity are
      unknown. To address this issue, we treated mouse brown preadipocytes with
      different doses of indomethacin, and delivered indomethacin to interscapular BAT
      (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose dependently
      increased brown preadipocyte differentiation and upregulated both mRNA and
      protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator
      activated receptor (PPAR) gamma coactivator 1-alpha. The mechanistic study showed
      that indomethacin significantly activated the reporter driven by the PPAR
      response element, indicating that indomethacin may work as a PPARgamma agonist in
      this cell line. Consistently, indomethacin significantly decreased iBAT mass and
      fasting blood glucose levels in high-fat diet-induced obesity (DIO) mice.
      Histologic analysis showed that brown adipocytes of indomethacin-treated mice
      contained smaller lipid droplets compared with control mice, suggesting that
      indomethacin alleviated the whitening of BAT induced by the high-fat diet.
      Moreover, indomethacin significantly increased UCP1 mRNA expression in iBAT.
      Taken together, this study indicates that indomethacin can promote mouse brown
      adipocyte differentiation, and might increase brown fat and glucose oxidation
      capacity in DIO mice.

PMID- 29567867
TI  - Reply to Fincher et al.: Conceptual specificity in dehumanization research is a
      feature, not a bug.

PMID- 29567866
TI  - Kruppel homolog 1 represses insect ecdysone biosynthesis by directly inhibiting
      the transcription of steroidogenic enzymes.
AB  - In insects, juvenile hormone (JH) and the steroid hormone ecdysone have opposing
      effects on regulation of the larval-pupal transition. Although increasing
      evidence suggests that JH represses ecdysone biosynthesis during larval
      development, the mechanism underlying this repression is not well understood.
      Here, we demonstrate that the expression of the Kruppel homolog 1 (Kr-h1), a gene
      encoding a transcription factor that mediates JH signaling, in ecdysone-producing
      organ prothoracic gland (PG) represses ecdysone biosynthesis by directly
      inhibiting the transcription of steroidogenic enzymes in both Drosophila and
      Bombyx Application of a JH mimic on ex vivo cultured PGs from Drosophila and
      Bombyx larvae induces Kr-h1 expression and inhibits the transcription of
      steroidogenic enzymes. In addition, PG-specific knockdown of Drosophila Kr-h1
      promotes-while overexpression hampers-ecdysone production and pupariation. We
      further find that Kr-h1 inhibits the transcription of steroidogenic enzymes by
      directly binding to their promoters to induce promoter DNA methylation. Finally,
      we show that Kr-h1 does not affect DNA replication in Drosophila PG cells and
      that the reduction of PG size mediated by Kr-h1 overexpression can be rescued by
      feeding ecdysone. Taken together, our data indicate direct and conserved Kr-h1
      repression of insect ecdysone biosynthesis in response to JH stimulation,
      providing insights into mechanisms underlying the antagonistic roles of JH and
      ecdysone.

PMID- 29567868
TI  - [Surgical Resection of Metastatic Brain Tumors:Risk of Local Recurrence and
      Leptomeningeal Dissemination, and Implications for Individualized Treatment].
AB  - Metastatic brain tumors are important complications in the overall management of
      cancers. We sought to determine the risk of local recurrence and leptomeningeal
      carcinomatosis(LC)in patients treated with surgical resection and adjuvant
      radiation therapy. We retrospectively reviewed 173 consecutive patients with
      metastatic brain tumors managed by surgical resection between 2002 and 2015 in a
      single institution. Eighty-seven percent of the patients underwent postoperative
      adjuvant radiotherapy. The median overall survival from surgery was 9.8 months.
      Thirty of 173 patients(17.3%)developed local recurrence and 14(8.1%)developed LC
      following surgery. Male sex(hazard ratio(HR): 2.8, 95% confidence interval(CI):
      1.0-10.0), colon cancer(HR: 6.5, 95% CI: 2.2-24.2), and no postoperative
      radiation(HR: 5.6, 95% CI: 2.1-13.7)were identified as risk factors of local
      recurrence in multivariate analysis. Female sex(HR: 4.4, 95% CI: 1.2-20.9)and
      recursive partitioning analysis(RPA)class 3(HR: 1.0e+9, 95%CI: 1.7-)were
      identified as risk factors of LC in multivariate analysis. Our retrospective
      review showed that individualized treatment with surgical resection followed by
      adjuvant radiation therapy is a safe and feasible method to control metastatic
      brain tumors in the real world.

PMID- 29567869
TI  - [Computational Fluid Dynamic Analysis of Intracranial Aneurysms Using Newly
      Developed Software:Can It Predict the Thin-Walled Region of Intracranial Aneurysm
      Preoperatively?]
AB  - OBJECT: Recent studies have shown that computational fluid dynamics(CFD)analysis
      is useful to evaluate flow dynamics of intracranial aneurysms. However, CFD
      analysis still requires high costs and substantial time even now. This study
      aimed to evaluate whether newly developed software can shorten the time for
      analysis and serve useful information during clipping surgery for intracranial
      aneurysms. METHODS: CFD analysis was performed in 55 unruptured cerebral
      aneurysms in 51 patients. The time required for analysis of each aneurysm was
      recorded. On the basis of CFD analysis, both pressure and wall shear
      stress(WSS)were calculated as the values at the systolic and diastolic phases,
      and also the mean value through one cardiac cycle. These data were compared
      between thin-wall points and other points within each aneurysm. RESULTS: The
      average time required for analysis was 3 hours, ranging from 1 to 15 hours. The
      CFD data could be referenced during surgery in each patient. The pressure in
      about 93% and 80% of the thin-wall points was higher than that at other points
      within each aneurysm in the systolic and diastolic phases, respectively. However,
      there was no significant correlation between WSS and wall thickness in each
      aneurysm. CONCLUSION: This study clearly shows that newly-developed software is
      simple and requires much shorter time for CFD analysis than previous methods.
      Higher pressure through the cardiac cycle may efficiently predict a thin-wall
      region within intracranial aneurysms, which strongly suggests that CFD analysis
      would be a valuable tool to determine the treatment strategy in patients with
      unruptured aneurysms.

PMID- 29567870
TI  - [Blister-like Aneurysm Originating from the Anterior Communicating Artery:A Case
      Report].
AB  - Blister-like aneurysms(BLA)are morphologically thin-walled fragile structures
      that are associated with a high risk of intraoperative rupture. BLAs presumably
      originate from an arterial dissection and often stem from a non-branching site on
      the supraclinoid segment of the internal carotid artery. We report a rare case of
      a patient who was successfully treated for a ruptured BLA originating from the
      anterior communicating artery(Acom). A 60-year-old woman presented with severe
      headache and loss of consciousness. Computed tomography(CT)showed diffuse
      subarachnoid hemorrhage(SAH), which was observed to be particularly dense in the
      interhemispheric fissure around the Acom. CT angiography and three dimensional
      digital subtraction angiography(DSA)did not show any aneurysms along the Acom.
      Follow-up DSA performed on day 13 showed a small aneurysmal dilatation of the
      Acom, which was surgically treated via interhemispheric approach.
      Intraoperatively, a BLA observed to be originating from the Acom was wrapped with
      a piece of temporal fascia using fibrin glue. Postoperatively, this patient
      showed a good clinical course without re-rupture. Follow-up DSA performed 5
      months after the occurrence of the SAH demonstrated disappearance of the BLA
      originating from the Acom. The findings in this patient strongly suggest that the
      pathomechanism of BLAs is attributable to an arterial dissection, which can often
      show morphological changes on short-term angiographic follow-up, and they
      demonstrate spontaneous repair. Thus, the therapeutic strategy to be utilized for
      the management of a BLA of the Acom should be carefully considered, because
      aneurysmal neck clipping or trapping can injure the Acom perforators and cause
      cognitive deficits. Further studies are needed to establish the optimal treatment
      strategy for the management of BLAs of the Acom.

PMID- 29567871
TI  - [Metastatic Brain Tumor from Lung Adenocarcinoma Presenting a Unique Radiographic
      Pattern during Afatinib Treatment:A Case Report].
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)are used as
      first-line treatment for patients with EGFR-mutated non-small cell lung
      cancer(NSCLC). Afatinib, a second-generation EGFR-TKI, is also effective against
      central nervous system(CNS)metastasis of NSCLC. However, patients treated with
      EGFR-TKI for many months may be at an increased risk of CNS metastasis due to the
      development of resistance in tumor cells to EGFR-TKI. The average period for
      development of resistance to EGFR-TKI is 8 to 10 months after the initiation of
      treatment. In the case presented herein, NSCLC showed a good clinical course in
      the 10 months following the initiation of afatinib;however, CNS metastasis
      progressed and presented unique findings on MR images. The lesions consisted of
      multiple cyst-like masses without gadolinium enhancement in the cerebellum and
      brain stem. The patient died within 2 months of the diagnosis of CNS metastasis.
      The resistance of tumor cells to afatinib may have occurred in the 10 months
      following the initiation of the treatment. Thus, CNS metastasis of NSCLC treated
      with afatinib may develop over a period of many months, exhibiting unique MRI
      findings, and deteriorate rapidly in some cases.

PMID- 29567872
TI  - [Tentorial Dural Arteriovenous Fistula Presenting with Ocular Symptoms:A Case
      Report].
AB  - Tentorial dural arteriovenous fistula(dAVF)is classified as Cognard 4 with a high
      risk of aggressive feature, such as intracranial hemorrhage, venous infarction,
      and intracranial hypertension. We report a rare case presenting with ocular
      symptoms caused by tentorial dAVF. A 59-year-old man presented with progressive
      chemosis and exophthalmos of his left eye. Angiography showed a tentorial dAVF
      that was primarily fed by the middle meningeal artery and the meningohypophyseal
      artery. The AVF drained into the superior ophthalmic vein and the cerebellar
      cortical vein via an enlarged petrosal vein. Because transarterial Onyx
      embolization resulted in incomplete obliteration of the fistula, he underwent
      microsurgery via a suboccipital approach to obliterate the shunt. Postoperative
      angiography showed complete obliteration of the shunt. His ocular symptoms
      rapidly cured. We present this rare case and discuss the pathomechanism
      associated with the development of ocular symptoms secondary to a tentorial dAVF
      from the viewpoint of microvascular anatomy.

PMID- 29567873
TI  - [Two Cases of Difficult-to-Treat Acute Epidural Hematoma and a Review of
      Decompressive Craniectomy with Hematoma Evacuation].
AB  - INTRODUCTION: Decompressive craniectomy(DC)with craniotomy for acute epidural
      hematoma(AEDH)removal is controversial. Here, we summarized two difficult AEDH
      cases where DC was performed. CASE 1:A 26-year-old man sustained a head injury in
      a bicycle accident, with a Japan Coma Scale(JCS)score of 200, right pupil
      mydriasis, and a left decerebrate posture on admission. Computed
      tomography(CT)revealed right AEDH with a midline shift. Craniotomy was performed
      without DC. Postoperatively, his consciousness level and anisocoria improved(JCS
      score, 30). Furthermore, no cerebral infarction was observed on CT at 9 h after
      surgery;however, at 48 h after surgery, a cerebral infarction with a mild midline
      shift was evident in the right hemisphere. His consciousness level
      deteriorated(JCS score, 100), and we initiated glyceol infusion. Worsening of the
      midline shift was apparent on CT 100 h after surgery;thus, DC was immediately
      performed. CASE 2:A 15-year-old boy was injured in a fall. On admission, his JCS
      score was 10. Immediately afterward, he showed neurological deterioration(JCS
      score, 200), right pupil mydriasis, and a left decorticate posture. CT revealed
      right AEDH with a midline shift;thus, craniotomy was performed with DC. On
      hospitalization day 10, he had orthostatic headache and a JCS score of 1. CT
      revealed paradoxical midline shift to the opposite side of craniotomy, and
      syndrome of the trephined was considered. He was placed in the Trendelenburg
      position until cranioplasty was performed on hospitalization day 18. CONCLUSION:
      Patients with AEDH presenting severe consciousness issues should undergo hematoma
      removal. Although DC is controversial, surgeons should administer intensive and
      prompt treatment according to the circumstance and should consider DC for
      appropriate AEDH cases.

PMID- 29567874
TI  - [A Case of Segmental Dysgenesis at the Terminal Portion(C1)of the Internal
      Carotid Artery with an Anomalous Collateral Vessel Containing Plexiform(Twig
      like)Networks as a Possible Cause of Intracerebral Hemorrhage].
AB  - A 65-year-old woman was transferred to our hospital because of loss of
      consciousness along with a right hemiplegia due to an intracerebral
      hematoma(ICH)that extended from the left temporal lobe to the lateral part of the
      basal ganglia. CT angiograms(CTA)and 3D-rotational angiograms showed an absence
      of the distal C1 segment of the left internal carotid artery(ICA), and an
      anomalous collateral vessel arising from the proximal end of the left A2 with
      plexiform(twig-like)arterial networks, supplying antegrade blood flow to the left
      middle cerebral artery territory. The caliber of the left carotid arterial system
      decreased from the origin to the terminal end. The source images of CTA revealed
      that the plexiform arteries were very close to the ICH, suggesting that the
      vessels might have caused the bleeding. Because a hypoplastic left carotid canal
      was observed, the segmental dysgenesis of the C1 portion of the left ICA seemed
      to have occurred during the early embryonic period. T2-weighted DRIVE images of
      MRI demonstrated the presence of a cord-like rudimentary structure corresponding
      to the distal C1 and proximal M1 portions. The patient was managed conservatively
      and was transferred to another hospital for subsequent rehabilitation. Segmental
      dysgenesis of the C1 portion is extremely rare. To our knowledge, only a single
      report has been published. The present findings suggest that 1)an anomalous
      collateral vessel corresponding to Heubner's artery evolved with residual
      primitive plexiform(twig-like)arterial networks and 2)this anomalous structure
      has not been proposed as a type of collateral systems for ICA dysgenesis.

PMID- 29567875
TI  - [(3)New Therapeutic Modalities using Seizure Detection Devices for Medically
      Refractory Epilepsy:AspireSR and the RNS System].

PMID- 29567876
TI  - From Editor's desk.

PMID- 29567877
TI  - A practical diagnostic approach to hepatic masses.
AB  - The differential diagnosis of hepatic mass lesions is broad and arriving at the
      right diagnosis can be challenging, especially on needle biopsies. The
      differential diagnosis of liver tumors in children is different from adults and
      is beyond the scope of this review. In adults, the approach varies depending on
      the age, gender, and presence of background liver disease. The lesions can be
      divided broadly into primary and metastatic (secondary), and the primary lesions
      can be further divided into those of hepatocellular origin and nonhepatocellular
      origin. The first category consists of benign and malignant lesions arising from
      hepatocytes, while the second category includes biliary, mesenchymal,
      hematopoietic, and vascular tumors. Discussion of nonepithelial neoplasms is
      beyond the scope of this review. The hepatocytic lesions comprise dysplastic
      nodules, focal nodular hyperplasia, hepatic adenoma, and hepatocellular
      carcinoma, and the differential diagnosis can be challenging requiring
      clinicopathological correlation and application of immunohistochemical (IHC)
      markers. Liver is a common site for metastasis, sometimes presenting with an
      unknown primary site, and proper workup is the key to arriving at the correct
      diagnosis. The correct diagnosis in this setting requires a systematic approach
      with attention to histologic features, imaging findings, clinical presentation,
      and judicious use of IHC markers. The list of antibodies that can be used for
      this purpose keeps on growing continually. It is important for pathologists to be
      up to date with the sensitivity and specificity of these markers and their
      diagnostic role and clinical implications. The purpose of this review is to
      outline the differential diagnosis of hepatic masses in adults and discuss an
      algorithmic approach to make a right diagnosis.

PMID- 29567878
TI  - Evaluation of the osteopontin in oral peripheral and central giant cell
      granuloma.
AB  - Aim: Peripheral giant cell granuloma (PGCG) and central giant cell granuloma
      (CGCG) of the jaws are benign proliferations of spindle-shaped mesenchymal cells
      and multinucleated giant cells. Despite the histopathologic similarities, they
      have markedly different clinical behavior. PGCG shows low recurrence rate whereas
      CGCG shows a variable clinical behavior ranging from nonaggressive lesions to
      aggressive lesions characterizing by pain, rapid growth, and high recurrence
      rate. Therefore, the aim of the study was to compare CGCG with PGCG by
      immunohistochemistry using Ki-67, osteopontin (OPN), and integrin
      alphavantibodies. Subjects and Methods: Twenty PGCG and 20 CGCG were selected for
      immunohistochemical evaluation of OPN, integrin alphav, and Ki-67 in
      multinucleated giant cells and mononucleated cells of PGCG and CGCG. Results:
      PGCG showed higher Ki-67 immunoreactivity in mononucleated cells compared to CGCG
      (P < 0.05). There was no reactivity with Ki-67 in multinucleated giant cells of
      both groups. Mononucleated cells in CGCGs demonstrated increased OPN and integrin
      alphavexpressions in comparison with PGCGs (P < 0.05). Conclusions: The clinic
      behavior of CGCG being more aggressive than PGCG might be explained by the high
      expression of OPN and integrin alphav. Further studies are necessary to evaluate
      the other OPN receptors and their role on the biologic behavior of these lesions.

PMID- 29567879
TI  - Role of calcium-sensing receptor, Galectin-3, Cyclin D1, and Ki-67
      immunohistochemistry to favor in the diagnosis of parathyroid carcinoma.
AB  - Background: As histopathological findings of parathyroid carcinoma are not
      certain, the diagnosis of tumors with degenerative changes may be difficult. In
      these cases, immunohistochemical markers are beneficial. We aimed to research the
      acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki
      67 as helpful markers in parathyroid tumors in cases which are difficult to
      diagnose. Materials and Methods: Those cases who had been diagnosed with atypical
      parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were
      reevaluated. Immunohistochemical markers were applied to this cases. Results:
      About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases
      were parathyroid carcinoma. According to the immunohistochemical results, global
      loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while
      there was no loss of staining in those with parathyroid adenoma (P = 0,001).
      Global loss of CaSR staining was found in only one out of 14 cases with atypical
      adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of
      carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21)
      of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be
      positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical
      adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation
      index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14)
      of those with atypical adenoma. Conclusion: In these studies, it has been
      emphasized that the global loss of CaSR staining was used as a negative marker in
      the diagnosis of carcinoma. In this study, we have also confirmed that the global
      loss of CaSR staining is a useful marker to determine potential increased
      malignancy.

PMID- 29567880
TI  - Myeloid cell leukemia-1 protein expression and myeloid cell leukemia-1 gene
      amplification in non small cell lung cancer.
AB  - Background: Myeloid cell leukemia-1 (Mcl-1) is a member of the B-cell lymphoma 2
      family known to play a significant role in the regulation of apoptosis. Mcl-1
      expression has been studied in nonsmall cell lung cancer (NSCLC) cell lines but
      has not been previously evaluated as a prognostic factor in clinical samples.
      Materials and Methods: Formalin-fixed, paraffin-embedded sections from 119 NSCLC,
      including 33 squamous cell carcinomas (SCC), 55 adenocarcinomas (AC), and 31
      either pure adenocarcinoma in situ (AIS) or AC with lepidic features were
      immunostained by an automated method with rabbit polyclonal Mcl-1. Cytoplasmic
      Mcl-1 (cMcl-1) immunoreactivity was scored based on intensity and percentage of
      positive tumor cells in both tumor and adjacent benign epithelium in each case.
      MCL1 amplification was determined by hybrid capture-based comprehensive genomic
      profiling (CGP) on a separate cohort of 9393 NSCLC samples. Results: Intense
      diffuse cMcl-1 overexpression was noted in 35/119 (29%) tumors overall and
      correlated with tumor type (52% AIS vs. 31% AC vs. 6% SCC, P < 0.0001), tumor
      grade (48% grade 1 vs. 14% grade 2 vs. 31% grade 3, P = 0.007), small tumor size
      (36% <=3.0 cm vs. 16% >3.0 cm, P = 0.016), and lengthened survival within the AIS
      subgroup (100% alive vs. 42% expired, P = 0.018) while showing a trend toward
      correlation with nonrecurrent disease overall (32% nonrecurrent vs. 11%
      recurrent, P = 0.072) and within the AC subgroup (33% nonrecurrent vs. 0%
      recurrent, P = 0.092). MCL1 amplification was identified in 569 (6%) of 9393
      NSCLC by CGP. Conclusions: cMcl-1 overexpression appears to occur independently
      from MCL1 gene amplification in NSCLC and correlates with AIS histologic type,
      lower tumor grade, smaller tumor size, nonrecurrent disease, and increased
      survival.

PMID- 29567881
TI  - Expression of breast cancer type 1 and its relation with expression of estrogen
      receptors, progesterone receptors, and human epidermal growth factor receptor
      2/neu in breast carcinoma on trucut biopsy specimens.
AB  - Objective: (1) The objective is to study the immunohistochemical expression of
      Breast cancer type 1 (BRCA1) in breast carcinoma on trucut biopsy specimens and
      (2) To relate its expression with that of estrogen receptors (ER), progesterone
      receptors (PR), and human epidermal growth factor receptor 2 (HER-2)/neu and the
      clinicopathological parameters. Settings and Design: A cross-sectional hospital
      based study was performed in Lady Hardinge Medical College and Shrimati Sucheta
      Kriplani Hospital, New Delhi, with collaboration of the Departments of Pathology
      and Surgery from the period of November 2008 to March 2010. Materials and
      Methods: The study group included 54 cytologically proven cases of breast
      carcinoma. The immunohistochemical expression of BRCA1 was studied and related
      with expression of ER, PR, and HER-2/neu on their trucut biopsies. Results: The
      altered expression of BRCA1 (i.e., reduced or absent expression) was seen in
      44.4% cases of breast carcinoma while 55.6% had positive expression. About 83% of
      breast carcinomas with altered BRCA1 expression were larger than 3 cm in size.
      The breast carcinomas showing altered expression were found to be mostly high
      grade (63.6%). This was statistically significant. The ER and PR negativity were
      seen in 62.5% and 79.2% breast carcinomas with altered BRCA1 expression,
      respectively. The score 3 positivity of HER-2/neu was more common among
      carcinomas with altered BRCA1 expression (21% vs. 16.7%). The triple negativity
      was found in 41.7% breast carcinomas having altered BRCA1 expression. This was
      statistically significant. Conclusion: The combination of immunohistochemical
      expression of BRCA1, ER, PR, and HER-2/neu and clinicopathological details may be
      helpful in predicting the individuals more likely to carry BRCA1 mutations and
      thus selecting the candidate and family members for genetic screening for BRCA1
      mutations.

PMID- 29567882
TI  - Immunohistochemical evaluation of lymphovascular invasion in carcinoma breast
      with CD34 and D2-40 and its correlation with other prognostic markers.
AB  - Background: Carcinoma breast is ever-evolving and becoming increasingly prevalent
      in India. Numerous prognostic factors based on morphology and
      immunohistochemistry (IHC) have been established which need to be interconnected
      to give patients best possible treatment. Aims: This study aims to confirm and
      analyze lymphovascular invasion (LVI) detected by hematoxylin and eosin (H and E)
      using IHC with CD34 and D2-40 and its correlation with other biologic and
      morphologic prognostic markers. Settings and Design: This was a prospective
      study. Materials and Methods: Fifty mastectomy specimens diagnosed as
      infiltrating ductal carcinoma breast on histopathology selected for the study.
      Evaluation of formalin-fixed paraffin-embedded sections was done using H and E
      and IHC for estrogen receptor (ER), progesterone receptor (PR), human epidermal
      growth factor receptor 2 HER2/neu receptors, CD34, and D2-40 endothelial markers.
      Correlation of LVI done with prognostic markers of Carcinoma Breast, namely, age
      of the patient, tumor size, Nottingham grade, lymph node ratio (LNR), Nottingham
      prognostic index (NPI), ER/PR status, and HER2/neu status. CD34 and D2-40
      utilized to distinguish blood vessel, lymph vessel, and retraction artifacts and
      to calculate lymphatic microvessel density (LMVD) and blood microvessel density
      (BMVD). Statistical Analysis Used: SPSS Software Package. Results: LVI was
      associated with younger age (P = 0.001), greater tumor size (P = 0.007), higher
      Nottingham grade (P = 0.001), higher LNR (P = 0.001), higher NPI (P = 0.001),
      Negative ER Status (P = 0.001), Negative PR Status (P = 0.002), Positive HER2/neu
      status (P = 0.021), Higher Intratumoral BMVD (P = 0.016), Peritumoral BMVD (P =
      0.001), and Intratumoral LMVD (P = 0.009). Blood vessels more commonly invaded
      than lymph vessels. Retraction artifacts can be mistaken for LVI without IHC.
      Conclusions: D2-40 is a promising marker for lymphatic endothelium. LVI is a poor
      prognostic marker hence should be evaluated imperatively in all cases of
      carcinoma breast.

PMID- 29567883
TI  - Liquid-based cytology versus conventional cytology in fine-needle aspirates of
      salivary gland neoplasms.
AB  - Background: Liquid-based cytology (LBC) is a method of retrieving and processing
      of cytological material for the assessment of both gynecological and
      nongynecological cases introduced in 1996. Mostly conventional smears (CS) are
      prepared in Indian scenario; however, due to increasing popularity of LBC in
      nongynecology specimens, LBC is also used in few centers for diagnosing salivary
      gland neoplasm. Aim: The aim of this study is to compare CS and LBC in fine
      needle aspiration cytology (FNAC) of the salivary gland neoplasms in terms of
      cytomorphological details, adequacy, ease of interpretation, pitfalls, and
      diagnostic efficiency. Materials and Methods: We conducted a prospective,
      observational, comparative study which included 64 salivary gland neoplasms. Both
      CS and LBC (SurePath) were prepared as per standard protocols and examined.
      Results and Conclusion: In our study, specificity and positive predictive value
      of both the techniques (conventional and LBC) were found to be 100%. Sensitivity
      of both the techniques was found to be similar (66.7%). Negative predictive value
      and diagnostic accuracy of conventional technique were found to be almost similar
      to that of LBC technique (97.6% vs. 97.2% and 97.7% vs. 97.4%). In terms of
      adequacy and cellularity, CSs were better than LBC. Ease of interpretation was
      better with CSs due to abundant chondromyxoid stroma, an important clue in the
      diagnosis of pleomorphic adenoma. Nuclear details and background were better in
      LBC as compared to CS. Hence, we conclude that in salivary gland FNAC, both CS
      and LBC have similar diagnostic efficiency. however, interpretation of
      conventional smears is easier than Liquid Based Cytology especially in cases of
      pleomorphic adenoma. However, some advantages of LBC in respect to conventional
      cytology, with better-preserved morphology obtained from LBC becomes furthermore
      obligatory.

PMID- 29567884
TI  - Utility of CD200 expression and CD20 antibody binding capacity in differentiating
      chronic lymphocytic leukemia from other chronic lymphoproliferative disorders.
AB  - Background: Chronic lymphoproliferative disorders (CLPDs) are heterogeneous group
      of disorders with variable clinical presentations and outcomes. Therefore,
      accurate classification is crucial for treatment planning. At present, flow
      cytometry immunophenotyping (FCM-IPT) is a useful tool for diagnosing these
      diseases. However, overlapping immunophenotypes do exist. Recently, differential
      expression of CD200 and variation in number of CD20 antibody bound per cell (ABC)
      in different CLPDs has been reported. Materials and Methods: Seventy-seven CLPD
      cases were analyzed by FCM-IPT for CD200 expression, and Quantibrite bead was
      used to calculate CD20 ABC. Results: Variability in CD200 expression can help in
      the differentiation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia
      (HCL) from other CLPDs. CD200 was brightly expressed in 100% CLL cases, having
      homogenous bright (2+) intensity. On the contrary, CD200 was uniformly negative
      in all Mantle cell lymphoma cases except 1, in which the intensity was dim, and
      the mean fluorescence intensity was significantly lower than CLL. Furthermore,
      all HCL cases showed bright expression of CD200, thereby making it useful in
      differentiation from other CLPD with villous lymphocytes. Evaluation of CD20 ABC
      showed that it differs among various CLPD and was significantly lowest in CLL and
      highest in HCL both on peripheral blood and bone marrow samples. Conclusion: Our
      results support the fact that CD200 can be added to routine CLPD panel as it is
      useful in subcategorizing them. However, inclusion of CD20 ABC to routine panel
      does not seem plausible but may be done for difficult diagnostic cases or where
      anti-CD20 therapy is planned.

PMID- 29567885
TI  - Applicability of 2008 World Health Organization classification system of
      hematolymphoid neoplasms: Learning experiences.
AB  - Background: 2008 World Health Organization (WHO) classification of hematolymphoid
      neoplasms (HLN) has classified them based on morphology, results of various
      ancillary techniques, and clinical features.[1] There are no studies looking at
      the applicability of WHO classification. Aims: The aim of the study was to
      calculate proportions of all HLN subtypes seen during 1-year period based on 2008
      WHO classification of HLN and study applicability and also shortcomings of
      practices in a tertiary care center in India. Materials and Methods: This was a 1
      year retrospective study (January 1st, to December 31st, 2010) where cases were
      identified using hospital/laboratory electronic records. Old follow-up and
      referral cases were excluded from the study. Only newly diagnosed cases
      classified into categories laid down by 2008 WHO classification of HLN included.
      Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were
      of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of
      histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias
      of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell
      lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177,
      48.2%) was the most common subtype within pediatric age group. Conclusions: All
      major subtypes of HLN were seen at our center and showed trends almost similar to
      those seen in other Indian studies. Molecular/cytogenetic studies could not be
      performed on a significant number of cases owing to logistic reasons
      (unavailability of complete panels and also cost-related issues) and such cases
      could not be classified as per the WHO classification system.

PMID- 29567886
TI  - CagA and VacA genes of Helicobacter pylori and their clinical relevance.
AB  - Context: : Helicobacter pylori is associated with the development of a variety of
      gastroduodenal diseases which varies with ethnicity and the type of strains that
      infect the population. Aims: This study aims to evaluate the prevalence of H.
      pylori cagA and vacA genotypes in our region and to determine their relationship
      to the severity of the lesions that they cause. Settings and Design: : This study
      was an observational cross-sectional study. Subjects and Methods: DNA was
      extracted from 165 gastric biopsies from patients evaluated for dyspepsia. PCR
      was used to detect cagA and vacA (s1, s2, m1, m2) genes of H. pylori. Statistical
      analysis of associations was performed between endoscopy findings and virulence
      genes. Statistical Analysis Used: Pearson Chi-square test and Fischer's exact
      test. Results: The prevalence of H. pylori infection was 37% and the dominant
      genotypes was vacA s1 cagA-positive strain (54.1%) in this study. The vacAs1
      subtype was found in all patients with peptic ulcer disease (PUD). The entire
      normal study group had VacA s2 variant only. This clearly shows that vacA s1 is a
      significant virulence marker and patients harboring s1 strains are more prone to
      develop ulcers (P = 0.007). There was a significant association of cagA with s1
      strain rather than s2. Variation in VacA m genotype did not seem to have any
      association with disease status. There was a statistically significant
      association between the presence of cagA gene and PUD rather than the nonulcer
      dyspepsia (P = 0.027). Conclusion: The predominant genotype in our population was
      cagA positive vacA s1, which was found to be significantly associated with
      patients with gastric diseases, especially PUD. VacA s1 can serve as a single
      best virulence marker of the disease manifestation.

PMID- 29567887
TI  - Role of nm23H1 in predicting metastases in prostatic carcinoma.
AB  - Background: Non-metastatic nm23H1 gene is thought to play a critical role in cell
      proliferation. Studies of nm23H1 have been done in many other malignancies. But
      none of these studies took up nm23H1 gene as predictor in the metastases of
      prostatic carcinoma. Aims and Objectives: To study the expression of nm23H1 in
      prostatic lesion and to correlate nm23H1 expression with presence of metastases,
      tumour stage, tumour grade and with PSA level serum. Setting and Design: Tertiary
      hospital based retrospective and prospective study done in a period of one year
      from thirty patients having prostatic lesion confirmed by biopsy. Material and
      Methods: Immunohistochemistry for nm23H1 was performed on unstained coated
      sections of prostatic lesions to study the relation with prostatic lesion and
      their correlation with age, PSA level, tumour stage, grading. Clinical data was
      collected from medical records. Statistical Analysis: SPSS Version 15 analysis
      software was used. The value were presented in number(%) and Mean +/- SD.
      Results: Majority of patients belong to age group 61 to 70yrs.Gleason score >7
      were seen in 55% of patients of adenocarcinoma with and without metastasis. The
      difference in PSA levels between BPH and adenocarcinoma was significant (P <
      0.001). IHC expression for nm23H1 gene showed positive findings in all the cases
      (P = 1). PSA values >20ng/ml showed maximum % mean expression (98.64%) as
      compared to PSA levels <10 ng/ml (96.91%). Conclusion: IHC expression of nm23H1
      is not an effective tool to distinguish among the cases of BPH, adenocarcinoma of
      prostate with and without metastasis. Hence nm23H1 gene does not behave like an
      antimetastatic gene in prostatic lesions.

PMID- 29567888
TI  - Prevalence of scrub typhus in pyrexia of unknown origin and assessment of
      interleukin-8, tumor necrosis factor-alpha, and interferon-gamma levels in scrub
      typhus-positive patients.
AB  - Background: Scrub typhus is lesser known cause of fever of unknown origin in
      India. Even if there have been reports documenting the prevalence of scrub typhus
      in different parts of India, it is still an unknown entity, and clinicians
      usually do not consider it as differential diagnosis. The present study was
      performed to document the prevalence of scrub typhus among febrile patients in
      western part of Uttar Pradesh and to assess the clinical profile of infected
      patients on the one hand and knowledge, attitude, and practices among clinicians
      on the other. Materials and Methods: A total of 357 adult patients with fever of
      more than 5-day duration were recruited. All patients underwent complete physical
      examination, and detailed clinical history was elicited as per predesigned pro
      forma. After primary screening to rule out malaria, enteric fever, and
      leptospirosis infection, secondary screening for scrub typhus was done by rapid
      screen test and IgM ELISA. Results: Scrub typhus infection was positive in 91
      (25.5%) cases. The most common symptoms among the patients were fever (100%),
      pain in abdomen (79.1%), pedal edema 56 (61.5%), rash 44 (48.3%), headache 44
      (48.3%), vomiting 42 (46.1%), constipation 33 (36.2%), cough 28 (30.7%), and
      lymphadenopathy 20 (21.9%). The median values of interleukin-8, interferon-gamma,
      and tumor necrosis factor-alpha in healthy controls were 15.54 pg/ml, 7.77 pg/ml,
      and 54.1 pg/ml, respectively, while the median values of these cytokines in scrub
      typhus-positive patients were 21.04 pg/ml, 8.74 pg/ml, and 73.8 pg/ml,
      respectively. Conclusion: Our results highlight that scrub typhus infection is an
      important cause of pyrexia of unknown origin, and active surveillance is
      necessary to assess the exact magnitude and distribution of the disease.

PMID- 29567889
TI  - Evaluation of procalcitonin as a diagnostic marker in neonatal sepsis.
AB  - Context: Neonatal sepsis is an early infection occurring within 28 days of the
      postnatal life. It has nonspecific signs and symptoms which make the diagnosis
      cumbersome. It inflicts an increase in morbidity and mortality among neonates.
      Procalcitonin (PCT) is yet another acute phase reactant, which is synthesized by
      the C-cells of thyroid gland. Aims: The aim of our study is to evaluate PCT as a
      diagnostic marker of neonatal sepsis in comparison with C-reactive protein (CRP).
      Subjects and Methods: A prospective cross-sectional study was conducted at our
      tertiary care hospital in Puducherry. The study was conducted over a period of 5
      months from November 2015 to 2016. The study included all neonates with clinical
      signs of sepsis. The neonates were assigned into three groups as proven sepsis,
      suspected sepsis, and no sepsis group. The CRP level and PCT level were compared
      between the three groups, and their sensitivity and specificity were calculated.
      Statistical Analysis Used: The mean, standard deviation, and standard error of
      mean were calculated. The groups were compared using one-way ANOVA. The
      diagnostic test efficiency was evaluated by receiver operating characteristic
      curve analysis. Results: A total of 75 neonates were included in our study. There
      were 9 (12%) neonates with proven clinical sepsis, 47 (62.6%) neonates with
      suspected clinical sepsis, and 19 (25.3%) neonates with no sepsis. The mean and
      standard error of mean were calculated for CRP and PCT in all the three groups.
      The results showed a sensitivity of 88.90% for both CRP and PCT and specificity
      of 89.40% for CRP and 80.30% for PCT. The common organisms isolated from culture
      positive group were Escherichia coli (22.2%), Pseudomonas aeruginosa (22.2%), and
      Candida albicans (22.2%), followed by Klebsiella pneumoniae, Acinetobacter
      baumannii, and methicillin-resistant Staphylococcus aureus. Conclusions: PCT may
      not be sufficiently used as a sole marker of sepsis in neonates compared to CRP.
      PCT in conjunction with CRP and other tests for septic screen can aid in better
      diagnosis of neonatal sepsis.

PMID- 29567890
TI  - A perplexing primary novel hilar lesion: Remember the pneumonic PPNHL!
AB  - A 60-year-old female presented with dyspnea, cough, and chest pain with a left
      hilar mass lesion. In our case, clinicoradiological correlation, bronchoscopy,
      and computed tomography-guided biopsy revealed the diagnosis of primary pulmonary
      non-Hodgkin's lymphoma (PPNHL) on histopathology and immunohistochemistry. We
      discuss the approach to hilar masses. PPNHL is a rare malignant lymphoma most
      common being mucosa-associated lymphoid tissue lymphoma. Various therapeutic
      options are available. The chemotherapy regimen consisting of CHOP
      (cyclophosphamide, doxorubicin, vincristine, prednisolone) is preferred.

PMID- 29567891
TI  - Utility of MOC-31 monoclonal antibody in differentiating metastatic
      adenocarcinoma cells and reactive mesothelial cells in effusion cytology.
AB  - In effusion cytology, a clear distinction between reactive mesothelial cells and
      metastatic adenocarcinoma cells is sometimes challenging mainly due to
      similarities in the cytomorphological features. In such cases for definitive
      diagnosis, paraffin-embedded cell block examination and immunohistochemistry are
      helpful in making this distinction. MOC-31 is one of the proposed immunomarker
      for adenocarcinoma cells. We undertook to evaluate the role of MOC-31 as a marker
      for identifying adenocarcinoma cells in effusion specimen. A total of 185
      paraffin-embedded cell blocks of effusion samples were identified, of these 111
      cases were of metastatic adenocarcinoma. MOC-31 was positive in 101 of the 111
      cases of metastatic adenocarcinoma. Minimal focal cytoplasmic staining was also
      seen in 7 of the 74 cases of reactive mesothelial cells, but these were taken
      negative as they did not show membrane positivity. The sensitivity and
      specificity of MOC-31 for metastatic adenocarcinoma cells were 92.5%, and 100%
      respectively, positive and negative predictive value (NPV) was 100% and 91.14%,
      respectively. MOC-31 can be used as a reliable marker in effusions for
      distinguishing metastatic adenocarcinoma from reactive mesothelial cases.

PMID- 29567892
TI  - Sporadic lymphangioleiomyomatosis with multiple atypical features: A case report
      and literature review.
AB  - Lymphangioleiomyomatosis (LAM) is a rare, genetically determined, progressive
      interstitial lung disease, which almost exclusively affects women, especially at
      the childbearing age. The initial symptoms and radiographic changes in a patient
      with LAM are always associated with the respiratory system. Here, we present a
      case of mediastinal and abdominal LAM of a 22-year-old male, where LAM cells are
      negative for human melanoma black-45 ( HMB-45). The report of this
      uncharacterized LAM case will make a significant contribution to the realization
      of LAM associated clinical features, diagnostic approaches, and its afterward
      treatments.

PMID- 29567893
TI  - Coats' disease - disease of the eye rarely encountered by pathologists.
AB  - Coats' Disease is an idiopathic condition of the eye affecting young children
      although it can be seen in adults. Most patients present early in life with
      unilateral decreased vision, strabismus or leukocoria. The most important
      differential diagnosis is unilateral retinoblastoma. In this study we report a
      case of coat's disease in an young girl, and evaluate histopathological and
      clinical findings.

PMID- 29567894
TI  - Merkel cell carcinoma with seborrheic keratosis: A unique association.
AB  - Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine
      carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The
      most frequently reported sites have been the head and neck, extremities, and
      trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small
      cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell
      carcinoma both morphologically and on IHC. The possible cell of origin was
      proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high
      chance of local recurrence, regional and distant spread. In recent times, Merkel
      cell polyomavirus has been implicated as the causative agent for this tumor. The
      same agent has a reported etiologic association with other skin lesions,
      including seborrheic keratosis.

PMID- 29567895
TI  - Invasive cutaneous mucormycosis in a preterm neonate presenting as a
      vesicobullous lesion.
AB  - Mucormycosis is a relatively rare fungal infection seen in immunocompromised
      patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates
      have been reported in literature. It is an aggressive disease with a mortality
      rate of around 64% in neonates, so a high index of suspicion is essential for
      rapid diagnosis and definitive treatment with broad-spectrum antifungals such as
      Amphotericin B. We present a case of a premature infant born at 25 weeks of
      gestation who developed vesicobullous lesions all over the body on day 5 of life.
      Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of
      mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain.

PMID- 29567896
TI  - Syringocystadenoma papilliferum and trichoblastoma arising in the nevus
      sebaceous.
AB  - Nevus sebaceous (NS) is a clinically common benign tumor and has a high potential
      to develop into a great diversity of neoplasms of epidermal and adnexal origins.
      However, it is a rare phenomenon of the coexistence in a single NS with two or
      more skin tumors. We report a case of a 58-year-old woman with two kinds of
      neoplastic proliferation including syringocystadenoma papilliferum and
      trichoblastoma arising in NS on the scalp.

PMID- 29567897
TI  - Strongyloides stercoralis hyperinfection in an unconscious diabetic patient with
      dermatomyositis.
AB  - A case of Strongyloides stercoralis hyperinfection in a patient with
      dermatomyositis and diabetes mellitus is herein reported. The case was a 60-year
      old female admitted due to watery diarrhea and unconsciousness. She had a 10-year
      history of chronic immunosuppressive therapy including methotrexate and
      prednisolone for dermatomyositis. Stool parasitological examination revealed
      numerous rhabditiform larvae of threadworm "S. stercoralis." Larva in stool
      sample was characterized by sequencing of mitochondrial DNA. After treatment with
      ivermectin, the patient recovered without evidence of S. stercoralis in follow-up
      stool samples. In endemic areas, stool examination for detection of S.
      stercoralis should be performed on a regular basis for all patients receiving
      immunosuppressive therapy, as early detection and treatment are necessary to
      minimize complications of severe strongyloidiasis.

PMID- 29567898
TI  - Kikuchi's disease (histiocytic necrotizing lymphadenitis): A rare presentation
      with acute kidney injury, peripheral neuropathy, and aseptic meningitis with
      cutaneous involvement.
AB  - Kikuchi's disease (KD) also known as histiocytic necrotizing lymphadenitis is
      rare, idiopathic, generally self-limited cause of lymphadenitis. We present a
      case of twenty year young female who presented in critically ill state with
      fever, cervical and axillary lymphadenopathy, rash, vomiting and altered
      sensorium and found to have neurological, hepatic, renal and dermatological
      involvement. Kikuchi's disease should be considered in differential diagnosis of
      fever and lymphadenopathy and though benign can sometimes present with multi
      organ involvement. It is because of rarity of this disease with unusual
      complications, present case is reported.

PMID- 29567899
TI  - Autopsy findings in an atypical case of occult massive fatal pulmonary embolism
      in a backdrop of hyperhomocysteinemia.
AB  - A 43-year-old apparently healthy male presented with fever and presyncope. He was
      suspected to have massive pulmonary thromboembolism based on the clinico
      biochemical profile. Despite aggressive thrombolytic therapy, he succumbed to his
      illness within 12 h of admission. Postmortem examination showed massive pulmonary
      thromboembolism and hyperhomocysteinemia with low high-density lipoproteins (HDL)
      cholesterol with antemortem blood sample. Herein, we report autopsy findings in a
      rare case of a young male with occult massive pulmonary thromboembolism without
      deep vein thrombosis, who had an atypical clinical presentation and was found to
      have underlying hyperhomocysteinemia and decreased HDLc. An acute, massive PE can
      present a diagnostic challenge due to the rate and severity of decompensation
      seen in afflicted patients. A high index of suspicion is required for early
      detection of pulmonary embolism in a young patient with atypical presentation and
      without obvious risk factors.

PMID- 29567900
TI  - Anastomosing hemangioma with extensive fatty stroma in the retroperitoneum.
AB  - Anastomosing hemangiomas are a recently recognized benign vascular neoplasm,
      first described by Montgomery and Epstein in 2009. A few cases have been
      described in the genitourinary tract, especially in the renal hilum. These are
      fairly well-demarcated lesions with lobules of sinusoidal-like capillaries lined
      by hobnail endothelial cells containing eosinophilic hyaline globules in the
      cytoplasm. Extramedullary hematopoiesis has been described in a few cases, along
      with large feeding vessels. A predominant adipocytic component has been described
      in only one case.[9] We describe a case of a retroperitoneal anastomosing
      hemangioma occurring in an extrarenal site in a 53-year-old female, followed by a
      review of the current literature.

PMID- 29567901
TI  - Mixed epithelial and stromal tumor - A solid-cystic renal neoplasm undergoing
      malignant transformation: A rare case report.
AB  - We present a case of 53-year-old female who came with the complaints of mass on
      the right side of the abdomen noticed 3 weeks back. There was no history of
      localized swelling or rise of temperature, no history of weight loss, or evening
      rise of temperature. On examination, there was a flank mass which was bimanually
      palpable and tender. Routine laboratory investigations were within normal limits,
      except for the presence of hematuria in routine urinalysis. Computed tomography
      scan abdomen revealed a large multiloculated solid-cystic mass lesion with
      septation in the right-sided kidney. Cystic renal cell carcinoma was suspected
      and conventional open right radical nephrectomy was done. Grossly, the tumor was
      solid-cystic containing blood-tinged fluid. Microscopy revealed a complex tumor
      with both epithelial and stromal proliferation and with the aid of
      immunohistochemistry a diagnosis of mixed epithelial and stromal tumor undergoing
      malignant transformation was concluded.

PMID- 29567902
TI  - A rare case of primary female urethral adenocarcinoma: Columnar type with colonic
      adenocarcinoma features.
AB  - Female urethral carcinoma is extremely rare and accounts for 0.02% of all women's
      cancers and <1% of cancers in the female genitourinary tract. Adenocarcinoma
      accounts for only 10% of urethral carcinomas in females. Due to their location,
      presentation is usually late and tumors are often missed on physical examination.
      As in this case, nonspecific symptoms in the early stages may delay the diagnosis
      in most patients. Herein, we present an extremely rare case of the columnar type
      of primary female urethral adenocarcinoma exhibiting colonic adenocarcinoma
      features which to the authors' best knowledge has not been reported to date. The
      present study emphasizes the importance of a careful clinical examination and
      also highlights the role of imaging studies, and biopsy in making an accurate
      preoperative diagnosis of this rare disease. The disease may have devastating
      sequelae due to local and metastatic involvement if not recognized and treated
      earlier.

PMID- 29567903
TI  - Uterine tumor resembling ovarian sex cord tumor: Histomorphological features.
AB  - Uterine tumors resembling ovarian sex cord tumors are rare neoplasms with varied
      histological and immunophenotypic profile, uncertain histiogenesis and biological
      behavior. A critical evaluation of histological features is essential for
      diagnosis and management of these cases.

PMID- 29567904
TI  - Primary rhabdomyosarcoma in ovary - Pathologist clinches it all.
AB  - Sarcomas are extremely complex and heterogeneous group of malignancies. However,
      exact categorization of the type of sarcoma is essential for the individualized
      approach for a given patient. It is mandatory that sarcomas should be treated in
      tertiary care centers with good pathology support and expertise. Here, we present
      an apt example of a young girl with large abdominal mass which was diagnosed as
      ovarian rhabdomyosarcoma (RMS). Besides, her excellent response to RMS regimen
      further reinforces the findings.

PMID- 29567905
TI  - Diminished CD40L expression on T-cells in a case of disseminated cryptococcosis.
AB  - X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of
      patients to disseminated cryptococcal infections primarily due to CD40L
      deficiency that causes defective cross talk between T- and B-cells, thus
      preventing class switching. In HIGM syndrome, serum IgM levels are elevated with
      severe reduction in serum immunoglobulin G (IgG) and IgA levels. In addition, the
      expression of CD40L (CD154) on in vitro-activated T-cells is severely reduced or
      absent. Here, we describe a rare, and perhaps, the first reported case in India
      of a 3-year-old male child with X-linked HIGM immunodeficiency syndrome who
      developed disseminated Cryptococcosis. Evaluation of the serum IgG profile of the
      patient revealed increased serum IgM levels with reduced IgG and IgA levels. Both
      the frequency and the function of T-cells, primarily CD40L on activated T-cells,
      showed weak expression suggestive of HIGM syndrome.

PMID- 29567907
TI  - Chondroid syringoma with extensive cystic change and focal syringometaplasia: A
      rare histomorphological finding.

PMID- 29567906
TI  - Nontuberculous mycobacterial empyema in an immunocompetent child.
AB  - Nontuberculous mycobacterium (NTM) species are mycobacterial species other than
      those belonging to the Mycobacterium Tuberculosis complex and Mycobacterium
      leprae. There are very few reports of NTM in immunocompetent children causing
      empyema. In this article, we report a 9-year-old immunocompetent girl who
      presented with Mycobacterium avium-intracellulare empyema.

PMID- 29567908
TI  - Diffuse esophageal submucosal retention cysts: An autopsy happenstance.

PMID- 29567909
TI  - Hypernucleate plasma cell: A rare morphological finding.

PMID- 29567911
TI  - Intestinal spirochetosis: The hue is the cue.

PMID- 29567910
TI  - Multiple myeloma or lymphoma? The increasing role of flow cytometry and serum
      free light chain assay.

PMID- 29567912
TI  - Mobile whole slide imaging with Indian twist.

PMID- 29567913
TI  - An unusual presentation of multiple congenital melanocytic nevi with a whole-body
      distribution.

PMID- 29567914
TI  - Suprasellar schwannoma: A rare occurence.

PMID- 29567915
TI  - Primary orbital plasmacytoma: An unusual presentation in an adolescent.

PMID- 29567916
TI  - Clear cell myeloma artefactual or real.

PMID- 29567918
TI  - Undiagnosed tubal high-grade serous carcinoma metastatic to synchronous benign
      ovarian Brenner tumor.

PMID- 29567917
TI  - Hyperheptaploidy in idiopathic thrombocytopenic purpura.

PMID- 29567919
TI  - Multilocular peritoneal inclusion cyst, rare occurrence in men: A case report.

PMID- 29567920
TI  - Effects of Dental Rehabilitation under General Anesthesia on Children's Oral
      Health-Related Quality of Life: Saudi Arabian Parents' Perspectives.
AB  - Aim: To determine whether dental treatment under general anesthesia (GA) would
      improve quality of life for children as reported by Saudi Arabian parents using a
      Parental-Caregivers Perceptions Questionnaire (P-CPQ) and a Family Impact Scale
      (FIS). Methods: Sixty-six parents completed P-CPQ and FIS scales four to eight
      weeks after their children (ages three to ten years) underwent comprehensive
      dental treatment under GA. Postoperative data were compared with baseline data
      gathered before GA using paired t-test at the 0.05 level of significance. The
      responsiveness of the P-CPQ and the FIS and the magnitude of changes in
      children's quality of life as a result of dental treatment were determined by
      calculating the effect size (ES). Cross-sectional construct validity and internal
      consistency were also examined using the pretreatment scores of the P-CPQ and the
      FIS scores. Results: The overall P-CPQ and FIS scores showed a significant
      decrease following treatment, concomitant with large ES in both scales and all
      their subscales with the exception of social wellbeing, which showed moderate ES
      (ES 0.59). The greatest relative changes were seen in the oral symptoms (ES 1.81)
      and the family activity (ES 1.57) subscales. Conclusion: Dental treatment under
      GA is associated with considerable improvement in children's quality of life as
      perceived by Saudi parents. The P-CPQ and the FIS scales are valid and responsive
      to changes resulting from dental treatment of young children affected by severe
      childhood caries.

PMID- 29567922
TI  - Six-Year Survival and Early Failure Rate of 2918 Implants with Hydrophobic and
      Hydrophilic Enossal Surfaces.
AB  - The aim of this chart review was to obtain an objective, quantitative assessment
      of the clinical performance of an implant line used in an implantological office
      setting. Implants with hydrophilic (INICELL) and hydrophobic (TST; both: Thommen
      Medical AG, Grenchen, Switzerland) enossal surfaces were compared and the
      cumulative implant survival rate was calculated. The data of 1063 patients that
      received 2918 implants (1337 INICELL, 1581 TST) was included. The average follow
      up time was 2.1 (1.1-5.4) years for INICELL and 4.5 (1.3-5.9) years for TST
      implants (Thommen Medical AG, Switzerland). In the reported period 7 implants
      with INICELL (0.5%) and 23 TST implants (1.5%) failed. This difference was
      statistically significant. The analysis of cases treated and followed up in a
      single implantological office for 6 years confirmed the very good clinical
      outcome that was achieved with both used implant lines. Within the limitations of
      this retrospective analysis, the overall early failure rate of the hydrophilic
      implants was significantly lower than that of hydrophobic implants. The use of
      hydrophilic implants allows the clinician to obtain less early failures, hence
      the interest of an up-to-date surface for the daily work of an implant practice.

PMID- 29567923
TI  - The Peri-Implant and Periodontal Microbiota in Patients with and without Clinical
      Signs of Inflammation.
AB  - Late implant failures, caused by the inflammation of surrounding tissues are a
      problem in implant dentistry. The path of bacterial transmission from teeth to
      implants is not completely understood. Therefore, the purpose of this study was
      to analyze intraindividual bacterial transmission characterizing subgingival
      microbiomes in teeth and implants, both in healthy subjects and in those with
      signs of periodontitis or peri-implantitis. Samples of peri-implant and dental
      sulcus fluid were collected. To identify the predominant microbiota, amplified
      fragments of bacterial 16S rRNA gene were separated by single strand conformation
      polymorphism analysis, sequenced and taxonomically classified. A total of 25
      different predominant genera were found in the diseased group and 14 genera in
      the healthy group. Species richness did not differ significantly between
      implants, neighboring teeth and teeth with largest probing depth in the diseased
      group. Additionally, no differences between teeth and implants in the healthy
      group were detected. In contrast, microbial diversity varied between the
      different sampling points. Species richness is similar in healthy and diseased
      sites, but the composition of the bacterial community differed within the
      individual subjects. The underlying analyses strongly suggest that complete
      transmission from neighboring teeth to implants is unlikely.

PMID- 29567924
TI  - Effect of Long-Term Consumption of Lactobacillus paracasei SD1 on Reducing Mutans
      streptococci and Caries Risk: A Randomized Placebo-Controlled Trial.
AB  - BACKGROUND: A previous study revealed Lactobacillus paracasei SD1, a probiotic
      strain, could reduce mutans streptococci (MS). The aim of this study was to
      evaluate the long-term effects of L. paracasei SD1 on the colonization of MS, and
      whether caries lesions developed. METHODS: After informed consent, 122 children
      were recruited and randomly assigned to the probiotic or control groups. The
      probiotic group received milk-powder containing L. paracasei SD1 and the control
      group received standard milk-powder once daily for six months. Salivary MS and
      lactobacilli were enumerated using differential culture at baseline and at three
      month intervals for 12 months. The persistence of L. paracasei SD1 was
      investigated using AP-PCR for DNA-fingerprinting. Oral health was examined at
      baseline and at the end of the study according to WHO criteria. RESULTS: The long
      term consumption could prolong colonization of L. paracasei SD1. Significantly
      reduced MS counts and increased lactobacilli levels were found among children in
      the probiotic group. There were less caries lesions in the probiotic group at the
      end of the study. A significant reduction of the development of new caries
      lesions (4.5 times) was observed in the high caries risk group but not in the low
      caries risk group. CONCLUSIONS: Results demonstrate that the long-term daily
      ingestion of the human-derived probiotic L. paracasei SD1 significantly reduces
      the number of MS and caries risk in the high caries group.

PMID- 29567925
TI  - Randomized Clinical Investigation of Titanium Implants with and without Platform
      Switching: Six Months' Radiographic and Clinical Outcome.
AB  - The aim of this study was to obtain a randomized, clinical and radiological
      comparison of implants with and without platform switching (PFS). The two
      compared titanium implant types differed only in the microgap position: test
      (PFS) or control (StE, no PFS). All implants were inserted in posterior regions
      and followed up for six months after abutment connection (AC). Twenty one
      patients with 21 PFS and 18 StE implants completed the six-month evaluation. No
      implant failed. One complication (exposed cap screw) was reported at AC. No
      statistically significant difference was observed between the marginal bone level
      of PFS and StE implants. Their bone level stabilized approximately 1 mm below the
      microgap. Based on the outcome of this short-term study with a limited number of
      patients, it seems unlikely that the optimal clinical and radiological outcome
      obtained with the tested standard implant (no PFS) can be improved by introducing
      an inward microgap shift (PFS).

PMID- 29567926
TI  - Arrested Pneumatization of the Sphenoid Sinus on Large Field-of-View Cone Beam
      Computed Tomography Studies.
AB  - Arrested pneumatization of the sphenoid sinus is a normal anatomical variant. The
      aim of this report is to define cone beam computed tomography (CBCT)
      characteristics of arrested pneumatization of sphenoid sinus in an effort to help
      differentiate it from invasive or lytic skull base lesions. Two cases are
      presented with incidental findings. Both studies, acquired for other diagnostic
      purposes, demonstrated unique osseous patterns that were eventually deemed to be
      anatomic variations in the absence of clinical signs and symptoms although the
      pattern of bone loss and remodeling was diagnosed as pneumatization of the
      sphenoid sinus by a panel of medical and maxillofacial radiologists following
      contrasted advanced imaging. It is important to differentiate arrested
      pneumatization of the sphenoid sinus from lesions, such as arachnoid
      granulations, acoustic neuroma, glioma, metastatic lesions, meningioma, or
      chordoma, to prevent unnecessary biopsies or exploratory surgeries that would
      consequently reduce treatment costs and alleviate anxiety in patients.

PMID- 29567927
TI  - Regeneration and Repair in Endodontics-A Special Issue of the Dentistry Journal.
AB  - Endodontics is a specialized discipline in dentistry that concerns the
      morphology, physiology, and pathology of the pulp-dentin complex, root, and peri
      radicular tissues. [...].

PMID- 29567928
TI  - Implant Supported Fixed Dental Prostheses Using a New Monotype Zirconia Implant-A
      Case Report.
AB  - Currently, titanium or specific titanium alloys are the most often used materials
      for the fabrication of dental implants. Many studies have confirmed the
      osseointegrative capacity and clinical long-term performance of moderately rough
      titanium implants. However, disadvantages have also been reported with regard to
      peri-implant infections and the titanium metal properties. Tooth colored ceramic
      implants have attracted the interest of clinicians since the end of the 1960s.
      Initially, alumina was used for the fabrication of ceramic implants; however, due
      to the poor biomechanical properties, alumina implants are not commercially
      available any more. Since end of the 1990s, zirconia has been established in
      dentistry due to its superior biomechanical properties compared to other oxide
      ceramics such as alumina. Currently, zirconia is the material of choice for the
      fabrication of ceramic implants. Zirconia implants show superior biocompatibility
      compared to titanium and other metals. Additionally, it has been reported that
      zirconia implants with a micro-rough surface topography show at least a
      comparable osseointegrative capacity and similar clinical survival rates to
      moderately rough titanium implants. The present case reports a fixed implant
      supported reconstruction of a large edentulous space with compromised local bone
      conditions using new monotype zirconia dental implants with a micro-rough surface
      topography.

PMID- 29567929
TI  - Management of Antithrombotic Agents in Oral Surgery Maria Martinez and Dimitrios
      A. Tsakiris.
AB  - Systemic anticoagulation with intravenous or oral anticoagulants and antiplatelet
      agents is an efficient treatment against thromboembolic or cardiovascular
      disease. Invasive dental procedures or oral surgery might be associated with
      bleeding complications if carried out under anticoagulants. Patients on vitamin K
      antagonists, new direct anticoagulants or antiplatelet agents having dental
      interventions with low-risk for bleeding do not need interruption of
      anticoagulation. In case of bleeding complications local hemostatic measures,
      such as local surgical sutures, fibrin glue, local antifibrinolytic treatment
      with tranexamic acid, or e-aminocaproic acid suffice to stop bleeding. In
      patients with high risk of bleeding an individual assessment of the benefit/risk
      ratio of interrupting anticoagulation should be carried out. Bridging the long
      term anticoagulation with short-term anticoagulants should be planned according
      to national or international guidelines. The introduction of the newer direct
      oral anticoagulants having more flexible pharmacokinetic properties has
      facilitated bridging, allowing short-term interruption without increasing the
      risk of relapsing thrombotic or cardiovascular events.

PMID- 29567930
TI  - A Study of the Management of Patients Taking Novel Oral Antiplatelet or Direct
      Oral Anticoagulant Medication Undergoing Dental Surgery in a Rural Setting.
AB  - PURPOSE: Novel oral antiplatelet (NOAP) (prasugrel and ticagrelor) and direct
      oral anticoagulant drugs (DOAC) (dabigatran, rivaroxaban and apixaban) have
      emerged in the last decade. This study was undertaken to determine current
      approaches taken to the management of patients taking these agents in dental
      practice in a remote and rural setting. METHODS: A small retrospective study was
      carried out in a small island population that identified patients taking one of
      the above drugs. All national health service and private dental records were
      examined to determine the type of treatment carried out and whether drug therapy,
      treatment plans or actual treatment were modified as a result of NOAP or DOAC
      therapy. In addition other outcomes such as referral to another service for
      advice or treatment and any adverse bleeding events were noted. RESULTS: 156
      dental encounters for 95 patients taking one of the drugs were identified.
      Significant events were identified in sixteen encounters and the management of
      patients taking each drug type differed significantly between cases but no
      patients returned with troublesome post-operative bleeding. CONCLUSIONS: The
      approaches taken by dental surgeons in Orkney in the management of the NOAPs and
      DOACs varied and this is likely to be a reflection of the limited literature
      available.

PMID- 29567931
TI  - Mineralization of Early Stage Carious Lesions In Vitro-A Quantitative Approach.
AB  - Micro computed tomography has been combined with dedicated data analysis for the
      in vitro quantification of sub-surface enamel lesion mineralization. Two
      artificial white spot lesions, generated on a human molar crown in vitro, were
      examined. One lesion was treated with a self-assembling peptide intended to
      trigger nucleation of hydroxyapatite crystals. We non-destructively determined
      the local X-ray attenuation within the specimens before and after treatment. The
      three-dimensional data was rigidly registered. Three interpolation methods, i.e.,
      nearest neighbor, tri-linear, and tri-cubic interpolation were evaluated. The
      mineralization of the affected regions was quantified via joint histogram
      analysis, i.e., a voxel-by-voxel comparison of the tomography data before and
      after mineralization. After ten days incubation, the mean mineralization
      coefficient reached 35.5% for the peptide-treated specimen compared to 11.5% for
      the control. This pilot study does not give any evidence for the efficacy of
      peptide treatment nor allows estimating the necessary number of specimens to
      achieve significance, but shows a sound methodological approach on the basis of
      the joint histogram analysis.

PMID- 29567932
TI  - Oral Candida Carriage and Morphotype Differentiation in Chronic Periodontitis
      Patients with and without Diabetes in the Indian Sub-Continent.
AB  - The aim of this study was to assess the oral Candida carriage and morphotype
      differentiation of Candida species in chronic periodontitis patients, with and
      without diabetes mellitus. This cross sectional study included 30 subjects in the
      age range of 40-60 years, who were divided into two groups: 15 chronic
      periodontitis only (CP) patients, and 15 chronic periodontitis patients with
      diabetes (CPD). Clinical measurements included plaque index (PI), gingival index
      (GI), probing depth (PD), clinical attachment level (CAL), and fasting blood
      sugar level (FBS). The unstimulated whole saliva samples were collected for
      fungal analysis. Candida carriage was analyzed by measuring colony forming units
      (CFU) following the culture of samples. Qualitative morphotype differentiation of
      Candida species from yeast to hyphal form was analyzed using Periodic acid-Schiff
      (PAS) staining. There was no statistically significant difference between CP and
      CPD groups for the periodontal parameters. However, a significantly higher
      Candida species CFU count was found in CPD (0.33 +/- 0.23) as compared to CP
      (0.05 +/- 0.04) group. This pilot study suggests that the occurrence of Candida
      species is higher in the saliva of chronic periodontitis patients with diabetes
      as compared to patients with chronic periodontitis alone.

PMID- 29567933
TI  - Advances in Implant Dentistry-A Special Issue of Dentistry Journal.
AB  - New knowledge is developing at a rapidly increasing rate in implant dentistry, as
      in other areas of medicine. [...].

PMID- 29567935
TI  - Normothermic Machine Perfusion versus Cold Storage of Liver in Pig Model: A Meta
      Analysis.
AB  - BACKGROUND Normothermic machine perfusion (NMP) is a novel strategy used for
      organ preservation. We aimed to determine the overall efficacy of NMP for liver
      preservation versus traditional static cold storage (CS). MATERIAL AND METHODS We
      performed a meta-analysis of the literature to evaluate the efficacy of NMP in
      experimental pig models of liver preservation. We use the standardized mean
      difference and 95% confidence intervals (CI) to calculate statistics and used the
      random effects model for the combined analysis of the results. RESULTS A total of
      16 studies from 12 published articles were included. The combined results showed
      that NMP significantly decreased alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), and hyaluronic acid levels in serum or perfusate,
      significantly increased bile production, and had a similar 5-7-days survival rate
      after liver transplantation compared with the CS group. CONCLUSIONS NMP provides
      superior graft preservation compared with CS in the pig model.

PMID- 29567934
TI  - Dentinogenic Specificity in the Preclinical Evaluation of Vital Pulp Treatment
      Strategies: A Critical Review.
AB  - Reviews on the clinical performance of vital pulp treatment strategies and
      capping materials repeatedly showed an insufficient grade of evidence concerning
      their therapeutic validity. The biological mechanisms underlying the regenerative
      potential of pulp-dentin complex have attracted much attention during the last
      two decades, since new pulp treatment modalities have been designed and tested at
      the preclinical level. It has been recognized that evaluation should be based on
      the specific ability of therapeutic interventions to signal recruitment and
      differentiation of odontoblast-like cells forming a matrix in a predentin-like
      pattern, rather than uncontrolled hard tissue deposition in a scar-like form. The
      aim of the present article was to critically review data from histological
      experimental studies on pulp capping, published during the last 7 decades. A
      comprehensive literature search covering the period from 1949 to 2015 was done
      using the Medline/Pubmed database. Inclusion of a study was dependent on having
      sufficient data regarding the type of capping material used and the unit of
      observation (human permanent tooth in vivo or animal permanent dentition; primary
      teeth were excluded). The post-operatively deposited matrix was categorized into
      three types: unspecified, osteotypic, or dentin-like matrix. One hundred fifty
      two studies were included in the final evaluation. Data from the present
      systematic review have shown that only 30.2% of the 152 experimental histological
      pulp capping studies described the heterogenic nature of the hard tissue bridge
      formation, including osteotypic and tubular mineralized tissue. Structural
      characteristics of the new matrix and the associated formative cells were not
      provided by the remaining 106 studies. Analysis showed that more careful
      preclinical evaluation with emphasis on the evidence regarding the dentinogenic
      specificity of pulp therapies is required. It seems that selection of appropriate
      vital pulp treatment strategies and pulp capping materials would be further
      facilitated in terms of their therapeutic validity if international consensus
      could be reached on a select number of mandatory criteria for tissue-specific
      dentinogenic events.

PMID- 29567936
TI  - Splenic Rupture as the First Manifestation of Babesia Microti Infection: Report
      of a Case and Review of Literature.
AB  - BACKGROUND Babesiosis is an emerging, tick-borne zoonosis caused by
      intraerythrocytic protozoa of the genus Babesia. Babesia microti is the main
      pathogen causing human disease and is endemic in the northeastern and upper
      midwestern parts of the USA. Severity of infection ranges from mild, self
      limited, febrile viral-like illness accompanied by nonspecific symptoms to life
      threatening infection complicated by severe hemolytic anemia, disseminated
      intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and
      renal or/and hepatic failure. Splenic rupture (SR) is a very rare but life
      threatening complication of severe B. microti infection. CASE REPORT A 79-year
      old female farmer from Wisconsin, USA was admitted during summer with hemorrhagic
      shock secondary to spontaneous splenic rupture. She was transfused with 3 units
      of packed red blood cells (PRBC) and underwent emergent splenectomy.
      Postoperatively, she recovered well and was discharged on postoperative day 4.
      However, she was re-admitted on postoperative day 10 for febrile hemolytic
      anemia. Further exposure history was obtained and was significant for multiple
      tick bites 8 weeks preceding the index hospitalization. She was promptly
      diagnosed with babesiosis and Lyme disease co-infection. She responded favorably
      to 10 days of azithromycin and atovaquone and 21 days of oral doxycycline.
      CONCLUSIONS Despite its rare occurrence, SR due to B. microti infection is a
      dreaded complication that can rapidly progress to hemorrhagic shock and death. In
      contrast to other complications of babesiosis, SR is not correlated with parasite
      burden or immune status of the affected host. Babesiosis should be considered as
      part of the differential diagnosis in patients from endemic areas presenting with
      atraumatic splenic rupture.

PMID- 29567937
TI  - Imatinib Affects the Expression of SLC22A1 in a Non-Linear Concentration
      Dependent Manner Within 24 Hours.
AB  - BACKGROUND Imatinib is actively transported into cells by the organic cation
      transporter (OCT1), encoded by SLC22A1. As a result, the expression of SLC22A1 is
      considered a prognostic marker for treatment with imatinib in patients with
      chronic myeloid leukemia (CML). Although limited, there is conflicting evidence
      indicating that imatinib may affect the expression of SLC22A1. However, thus far,
      no studies have investigated the effect of imatinib on SLC22A1 expression in an
      imatinib-sensitive cell line, which would mimic a typical clinical setting.
      Changes in the expression of SLC22A1 as a result of imatinib could potentially
      negate its usefulness as a prognostic marker. MATERIAL AND METHODS The K562 CML
      cell line was exposed to varying concentrations of imatinib for 24, 48, and 72 h
      and SLC22A1 expression was determined by quantitative real-time PCR. RESULTS Our
      findings suggest that imatinib affects the expression of SLC22A1 within 24 h in a
      non-linear concentration-dependent manner. CONCLUSIONS This is the first study to
      report on the short-term effect of imatinib on the expression of SLC22A1 in an
      imatinib-sensitive CML cell line. Our results suggest that imatinib affects
      SLC22A1 mRNA expression in a non-linear dose-dependent manner and that the
      changes in the expression of SLC22A1 as a result of the concentration of imatinib
      occur within 24 h of exposure to imatinib and remain stable thereafter for up to
      72 h.

PMID- 29567938
TI  - Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte
      Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor
      Survival.
AB  - BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the
      mainstay of therapy for many years. Although adding anti-angiogenic drugs to
      chemotherapy improves patient survival slightly, identifying anti-angiogenic
      therapy-sensitive patients remains challenging for oncologists. Granulocyte
      colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which
      can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential
      tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient
      survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were
      collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40
      paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and
      G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical
      characteristics, VEGF-A levels and overall survival were analyzed. Biological
      function and underlying mechanistic investigations were carried out using SGC7901
      cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube
      formation were examined. RESULTS The levels of G-CSFR were upregulated in GC
      tissues compared to normal mucosa tissues. Higher G-CSF expression was associated
      with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas
      higher G-CSFR expression was associated with lymph node metastasis. Patients with
      higher G-CSF expression had shorter overall survival times. In vitro, G-CSF
      stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and
      accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G
      CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by
      stimulating tumor proliferation, migration, and angiogenesis, indicating that
      these factors are potential tumor targets for cancer treatment.

PMID- 29567939
TI  - Surface tension-assisted additive manufacturing.
AB  - The proliferation of computer-aided design and additive manufacturing enables on
      demand fabrication of complex, three-dimensional structures. However, combining
      the versatility of cell-laden hydrogels within the 3D printing process remains a
      challenge. Herein, we describe a facile and versatile method that integrates
      polymer networks (including hydrogels) with 3D-printed mechanical supports to
      fabricate multicomponent (bio)materials. The approach exploits surface tension to
      coat fenestrated surfaces with suspended liquid films that can be transformed
      into solid films. The operating parameters for the process are determined using a
      physical model, and complex geometric structures are successfully fabricated. We
      engineer, by tailoring the window geometry, scaffolds with anisotropic mechanical
      properties that compress longitudinally (~30% strain) without damaging the
      hydrogel coating. Finally, the process is amenable to high cell density
      encapsulation and co-culture. Viability (>95%) was maintained 28 days after
      encapsulation. This general approach can generate biocompatible, macroscale
      devices with structural integrity and anisotropic mechanical properties.

PMID- 29567940
TI  - Bax retrotranslocation potentiates Bcl-xL's antiapoptotic activity and is
      essential for switch-like transitions between MOMP competency and resistance.
AB  - The rapid, typically all-or-none process of mitochondrial outer membrane
      permeabilization (MOMP) constitutes a primary cell death decision that is
      controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP
      decisions are governed by and emanate from the dynamic interplay of pro- and
      antiapoptotic Bcl-2 family members remains incompletely understood. In
      particular, it is unclear to which extent the shuttling of Bcl-2 family species
      between lipid and aqueous phases contributes to regulating MOMP sensitivity.
      Here, we studied the interplay of tBid, Bax, and Bcl-xL, using a combined
      approach of deterministic mathematical modeling and retrospective as well as
      prospective experimental testing of model predictions. Systems modeling of the
      tBid-Bax interplay and their fluxes between cytosol and mitochondrial membranes
      reproduced experimental data on tBid-triggered Bax activation and oligomerization
      highly accurately. Extending these studies to analyze the cell-protective role of
      Bcl-xL strikingly revealed that the activity of Bcl-xL to retrotranslocate
      activated Bax from membranes back into the cytosol is essential to reproduce or
      correctly predict experimental outcomes. These included the potency of Bcl-xL in
      suppressing Bax oligomerization, its role in limiting Bax membrane recruitment,
      the resistance threshold to low concentrations of MOMP triggers as well as a
      response potentiaton arising from combinations of tBid and sensitizer BH3-only
      peptides. Importantly, retrotranslocation activity of Bcl-xL is necessary to
      strictly separate conditions of MOMP competency and resistance. Our results
      therefore identify Bax retrotranslocation by Bcl-xL as an indispensable component
      of the molecular switch by which Bcl-2 family members govern cellular death
      decisions.

PMID- 29567942
TI  - High temperature measurements and condensed matter analysis of the thermo
      physical properties of ThO2.
AB  - Values are presented for thermal conductivity, specific heat, spectral and total
      hemispherical emissivity of ThO2 (a potential nuclear fuel material) in a
      temperature range representative of a nuclear accident - 2000 K to 3050 K. For
      the first time direct measurements of thermal conductivity have been carried out
      on ThO2 at such high temperatures, clearly showing the property does not decrease
      above 2000 K. This could be understood in terms of an electronic contribution
      (arising from defect induced donor/acceptor states) compensating the degradation
      of lattice thermal conductivity. The increase in total hemispherical emissivity
      and visible/near-infrared spectral emissivity is consistent with the formation of
      donor/acceptor states in the band gap of ThO2. The electronic population of these
      defect states increases with temperature and hence more incoming photons (in the
      visible and near-infrared wavelength range) can be absorbed. A solid state
      physics model is used to interpret the experimental results. Specific heat and
      thermal expansion coefficient increase at high temperatures due to the formation
      of defects, in particular oxygen Frenkel pairs. Prior to melting a gradual
      increase to a maximum value is predicted in both properties. These maxima mark
      the onset of saturation of oxygen interstitial sites.

PMID- 29567941
TI  - Engineering enhanced cellobiohydrolase activity.
AB  - Glycoside Hydrolase Family 7 cellobiohydrolases (GH7 CBHs) catalyze cellulose
      depolymerization in cellulolytic eukaryotes, making them key discovery and
      engineering targets. However, there remains a lack of robust structure-activity
      relationships for these industrially important cellulases. Here, we compare CBHs
      from Trichoderma reesei (TrCel7A) and Penicillium funiculosum (PfCel7A), which
      exhibit a multi-modular architecture consisting of catalytic domain (CD),
      carbohydrate-binding module, and linker. We show that PfCel7A exhibits 60%
      greater performance on biomass than TrCel7A. To understand the contribution of
      each domain to this improvement, we measure enzymatic activity for a library of
      CBH chimeras with swapped subdomains, demonstrating that the enhancement is
      mainly caused by PfCel7A CD. We solve the crystal structure of PfCel7A CD and use
      this information to create a second library of TrCel7A CD mutants, identifying a
      TrCel7A double mutant with near-equivalent activity to wild-type PfCel7A.
      Overall, these results reveal CBH regions that enable targeted activity
      improvements.

PMID- 29567943
TI  - Peptide ion channel toxins from the bootlace worm, the longest animal on Earth.
AB  - Polypeptides from animal venoms have found important uses as drugs,
      pharmacological tools, and within biotechnological and agricultural applications.
      We here report a novel family of cystine knot peptides from nemertean worms, with
      potent activity on voltage-gated sodium channels. These toxins, named the alpha
      nemertides, were discovered in the epidermal mucus of Lineus longissimus, the
      'bootlace worm' known as the longest animal on earth. The most abundant peptide,
      the 31-residue long alpha-1, was isolated, synthesized, and its 3D NMR structure
      determined. Transcriptome analysis including 17 species revealed eight alpha
      nemertides, mainly distributed in the genus Lineus. alpha-1 caused paralysis and
      death in green crabs (Carcinus maenas) at 1 ug/kg (~300 pmol/kg). It showed
      profound effect on invertebrate voltage-gated sodium channels (e.g. Blattella
      germanica Nav1) at low nanomolar concentrations. Strong selectivity for insect
      over human sodium channels indicates that alpha-nemertides can be promising
      candidates for development of bioinsecticidal agents.

PMID- 29567944
TI  - Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity.
AB  - Development of metabolic syndrome is associated with hyperactivity of the HPA
      axis characterized by elevated levels of circulating adrenal hormones including
      cortisol and aldosterone. However, the molecular mechanism leading to the
      dysregulation of the HPA axis is not well elucidated. In this study, we found
      that insulin regulates adrenal steroidogenesis by increasing the expression and
      activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this
      insulin effect was partly through inhibition of FoxO1. Specifically, insulin
      increased the protein and RNA levels of SF-1 and steroidogenic target genes.
      Further, adrenal SF-1 expression was significantly increased by hyperactivation
      of insulin signaling in mice. Together with the elevated SF-1 expression in
      adrenal glands, hyperactivation of insulin signaling led to increased aldosterone
      and corticosterone levels. On the other hand, suppressing the insulin signaling
      using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In
      addition, overexpression of FoxO1 significantly suppressed SF-1 and its
      steroidogenic target genes implying that the positive effect of insulin on SF-1
      activity might be through suppression of FoxO1 in the adrenal gland. Taken
      together, these results indicate that insulin regulates adrenal steroidogenesis
      through coordinated control of SF-1 and FoxO1.

PMID- 29567945
TI  - The role of cuticular hydrocarbons in mate recognition in Drosophila suzukii.
AB  - Cuticular hydrocarbons (CHCs) play a central role in the chemical communication
      of many insects. In Drosophila suzukii, an economically important pest insect,
      very little is known about chemical communication and the possible role of CHCs.
      In this study, we identified 60 CHCs of Drosophila suzukii and studied their
      changes in function of age (maturation), sex and interactions with the opposite
      sex. We demonstrate that age (maturation) is the key factor driving changes in
      the CHC profiles. We then test the effect on courtship behaviour and mating of
      six CHCs, five of which were positively associated with maturation and one
      negatively. The results of these experiments demonstrate that four of the major
      CHC peaks with a chain length of 23 carbons, namely 9-tricosene (9-C23:1), 7
      tricosene (7-C23:1), 5-tricosene (5-C23:1) and tricosane (n-C23), negatively
      regulated courtship and mating, even though all these compounds were
      characteristic for sexually mature flies. We then go on to show that this effect
      on courtship and mating is likely due to the disruption of the natural ratios in
      which these hydrocarbons occur in Drosophila suzukii. Overall, these results
      provide key insights into the cuticular hydrocarbon signals that play a role in
      D. suzukii mate recognition.

PMID- 29567946
TI  - Evidence for a dyadic motor plan in joint action.
AB  - What mechanisms distinguish interactive from non-interactive actions? To answer
      this question we tested participants while they took turns playing music with a
      virtual partner: in the interactive joint action condition, the participants
      played a melody together with their partner by grasping (C note) or pressing (G
      note) a cube-shaped instrument, alternating in playing one note each. In the non
      interactive control condition, players' behavior was not guided by a shared
      melody, so that the partner's actions and notes were irrelevant to the
      participant. In both conditions, the participant's and partner's actions were
      physically congruent (e.g., grasp-grasp) or incongruent (e.g., grasp-point), and
      the partner's association between actions and notes was coherent with the
      participant's or reversed. Performance in the non-interactive condition was only
      affected by physical incongruence, whereas joint action was only affected when
      the partner's action-note associations were reversed. This shows that task
      interactivity shapes the sensorimotor coding of others' behaviors, and that joint
      action is based on active prediction of the partner's action effects rather than
      on passive action imitation. We suggest that such predictions are based on Dyadic
      Motor Plans that represent both the agent's and the partner's contributions to
      the interaction goal, like playing a melody together.

PMID- 29567947
TI  - Metal-organic framework and Tenax-TA as optimal sorbent mixture for concurrent GC
      MS analysis of C1 to C5 carbonyl compounds.
AB  - We report a multi adsorbent-based method using combinations of metal-organic
      frameworks (MOFs) and a commercial sorbent Tenax-TA for sampling and thermal
      desorption (TD) gas chromatography-mass spectrometry (GC-MS) quantification of
      mixtures of six (C1 to C5) aldehydes. The feasibility of this approach was
      demonstrated along with the optical analytical conditions for maximum recovery.
      Optimal TD conditions for adsorption and desorption of aldehydes using MOF-5 (Zn
      based MOF)+ Tenax-TA were determined as -25  degrees C and 150  degrees C,
      respectively (purge volume: 100 ml). These conditions yielded good linearity (R2
      = 0.997), precision, and high sensitivity. Analysis of the aldehyde mixtures
      yielded slightly smaller R2 values than the analysis of single species.
      Additionally, the performance of MOF-5+ Tenax-TA was compared with other
      combinations comprising of Cu-based MOF-199 and Zr-based MOF of UiO-66 topology.
      The results of the theoretical modelling analyses propose simultaneous
      interaction of the C=O group of aldehydes with open metal sites of the studied
      MOFs and van der Waals interaction of hydrocarbon "tail" of aldehydes with
      linkers of MOFs. The combined interactions significantly increased the enthalpy
      (eV/molecule) of formaldehyde adsorption on MOF. Our findings unravel a potential
      way to extend the application of GC-based detection toward concurrent analysis of
      organic molecules of variable sizes.

PMID- 29567948
TI  - Structural Implications of Mutations Conferring Rifampin Resistance in
      Mycobacterium leprae.
AB  - The rpoB gene encodes the beta subunit of RNA polymerase holoenzyme in
      Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were
      identified as etiological factors for rifampin resistance in leprosy. In the
      present study, we identified mutations corresponding to rifampin resistance in
      relapsed leprosy cases from three hospitals in southern India which treat leprosy
      patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy
      non-respondent leprosy cases, and PCR was performed to amplify the 276 bp
      rifampin resistance-determining region of the rpoB gene. PCR products were
      sequenced, and mutations were identified in four out of the 35 cases at codon
      positions D441Y, D441V, S437L and H476R. The structural and functional effects of
      these mutations were assessed in the context of three-dimensional comparative
      models of wild-type and mutant M. leprae RNA polymerase holoenzyme (RNAP), based
      on the recently solved crystal structures of RNAP of Mycobacterium tuberculosis,
      containing a synthetic nucleic acid scaffold and rifampin. The resistance
      mutations were observed to alter the hydrogen-bonding and hydrophobic
      interactions of rifampin and the 5' ribonucleotide of the growing RNA transcript.
      This study demonstrates that rifampin-resistant strains of M. leprae among
      leprosy patients in southern India are likely to arise from mutations that affect
      the drug-binding site and stability of RNAP.

PMID- 29567949
TI  - Ocimum flavone Orientin as a countermeasure for thrombocytopenia.
AB  - Thrombocytopenia or chronic depletion of platelets in blood, could create life
      threatening conditions in patients who receive aggressive systemic radiation and
      chemotherapy. Currently there are no approved agents for the rapid treatment of
      thrombocytopenia. In the present study, we demonstrate that administration of
      Orientin, a glycosidic flavonoid or dietary administration of Orientin containing
      Tulsi (Holy Basil) leaves, results in a significant increase in circulating
      platelets in a clinically relevant mouse model. No noticeable effects were
      observed on red blood cells, white blood cells or other hematologic parameters in
      treated animals indicating that Orientin specificity enhances platelet formation.
      The gene expression and immunophenotyping of bone marrow revealed that Orientin
      stimulates megakaryopoiesis specific transcriptional program. A significant
      increase in colony formation in bone marrow cells from Orientin pretreated mice
      further complemented the effect of Orientin on progenitor cells. The ex-vivo
      differentiation of irradiated human peripheral blood CD34+ stem cells
      demonstrated stimulatory effects of Orientin on megakaryocyte erythrocyte
      progenitors (MEP). The results show that Orientin, a non-toxic readily available
      natural product can counter platelet imbalances. Thrombocytopenia also develop as
      a consequence of multiple hematologic malignancies and side effects of
      treatments. Dietary supplementation of Orientin containing phytochemicals could
      be effective as countermeasures and viable therapeutics.

PMID- 29567950
TI  - Understanding the molecular biology of intervertebral disc degeneration and
      potential gene therapy strategies for regeneration: a review.
AB  - Intervertebral disc degeneration (IVDD) is a multi-factorial process
      characterized by phenotypic and genotypic changes, which leads to low back pain
      and disability. Prolonged imbalance between anabolism and catabolism in discs
      alters their composition resulting in progressive loss of proteoglycans and
      hydration leading to IVDD. The current managements for IVDD are only able to
      relieve the symptoms but do not address the underlying pathology of degeneration.
      Researchers have tried to find out differences between the aging and degeneration
      of the disc. Intense attempts are in progress for identifying the various factors
      responsible for disc degeneration, as well as strategies for regeneration.
      Recently biological approaches have gained thrust in the field of IVDD. The
      present review illustrates the current understanding of intervertebral disc
      degeneration and aims to put forth recent advancements in regeneration strategies
      involving different biological therapies such as growth factor, cell, and gene
      therapy. The potentials and consequences of these therapies are also extensively
      discussed along with citing the most suitable method, that is, the gene therapy
      in detail. Initially, gene therapy was mediated by viral vectors but recent
      progress has enabled researchers to opt for non-virus-mediated gene therapy
      methods, which ensure that there are no risks of mutagenicity and infection in
      target cells. With constant efforts, non-virus-mediated gene therapy may prove to
      be an extremely powerful tool in treatment of IVDD in future.

PMID- 29567951
TI  - Identification of potential key protein interaction networks of BK virus
      nephropathy in patients receiving kidney transplantation.
AB  - We aim to identify the key protein interaction networks and implicated pathways
      of BK virus nephropathy (BKVN) via bioinformatic methods. The microarray data
      GSE75693 of 30 patients with stable kidney transplantation and 15 with BKVN were
      downloaded and analyzed by using the limma package to identify differentially
      expressed genes (DEGs). Then the gene ontology (GO) functional enrichment
      analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis
      were done to investigate the molecular function (MF), biological process (BP),
      cellular components (CC) and pathways of DEGs. Finally, protein-protein
      interactions (PPIs) were constructed, and the hub proteins were  identified. As a
      result, 249 up-regulated genes and 253 down-regulated genes of BKVN patients were
      selected based on criteria of P > 0.01 and fold change >2.0. GO and KEGG showed
      that DEGs were mainly located in nucleus and cytosol, and were implicated in the
      immune responses. In the PPI analysis, 26 up-regulated and 8 down-regulated
      proteins composed the pivotal interaction network. CXCL10, EGF and STAT1 were
      identified as hub proteins in BKVN. In conclusion, CXCL10, EGF and STAT1 may
      induce kidney injuries by promoting inflammation and prohibiting reparation of
      tissue damage in BKVN.

PMID- 29567952
TI  - Cystargamide B, a cyclic lipodepsipeptide with protease inhibitory activity from
      Streptomyces sp.
AB  - We identified a new cyclic lipodepsipeptide, cystargamide B (1), from the
      mycelial extract of a Kaempferia galanga rhizome-derived actinomycete strain,
      Streptomyces sp. PB013. The planar structure was elucidated based on high
      resolution fast-atom bombardment mass spectrometry (HRFABMS) spectroscopy and one
      dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR)
      spectroscopic data. The absolute configurations of the constituent amino acids
      were determined using advanced Marfey's method. Cystargamide B (1) includes rare
      structural units: a 5-hydroxytryptophan residue and a 2,3-epoxy fatty acid side
      chain. Notably, cystargamide B (1) inhibited the protease activity of the
      NS2B/NS3 complex from dengue virus.

PMID- 29567953
TI  - Ruthenium(II)-enabled para-selective C-H difluoromethylation of anilides and
      their derivatives.
AB  - Transition-metal-catalyzed direct site-selective functionalization of arene C-H
      bonds has emerged as an innovative approach for building the core structure of
      pharmaceutical agents and other versatile complex compounds. However, para
      selective C-H functionalization has seldom been explored, only a few examples,
      such as steric-hindered arenes, electron-rich arenes, and substrates with a
      directing group, have been reported to date. Here we describe the development of
      a ruthenium-enabled para-selective C-H difluoromethylation of anilides,
      indolines, and tetrahydroquinolines. This reaction tolerates various substituted
      arenes, affording para-difluoromethylation products in moderate to good yields.
      Results of a preliminary study of the mechanism indicate that chelation-assisted
      cycloruthenation might play a role in the selective activation of para-CAr-H
      bonds. Furthermore, this method provides a direct approach for the synthesis of
      fluorinated drug derivatives, which has important application for drug discovery
      and development.

PMID- 29567954
TI  - A new caenagnathid dinosaur from the Upper Cretaceous Wangshi Group of Shandong,
      China, with comments on size variation among oviraptorosaurs.
AB  - The bone-beds of the Upper Cretaceous Wangshi Group in Zhucheng, Shandong, China
      are rich in fossil remains of the gigantic hadrosaurid Shantungosaurus. Here we
      report a new oviraptorosaur, Anomalipes zhaoi gen. et sp. nov., based on a
      recently collected specimen comprising a partial left hindlimb from the Kugou
      Locality in Zhucheng. This specimen's systematic position was assessed by three
      numerical cladistic analyses based on recently published theropod phylogenetic
      datasets, with the inclusion of several new characters. Anomalipes zhaoi differs
      from other known caenagnathids in having a unique combination of features:
      femoral head anteroposteriorly narrow and with significant posterior orientation;
      accessory trochanter low and confluent with lesser trochanter; lateral ridge
      present on femoral lateral surface; weak fourth trochanter present; metatarsal
      III with triangular proximal articular surface, prominent anterior flange near
      proximal end, highly asymmetrical hemicondyles, and longitudinal groove on distal
      articular surface; and ungual of pedal digit II with lateral collateral groove
      deeper and more dorsally located than medial groove. The holotype of Anomalipes
      zhaoi is smaller than is typical for Caenagnathidae but larger than is typical
      for the other major oviraptorosaurian subclade, Oviraptoridae. Size comparisons
      among oviraptorisaurians show that the Caenagnathidae vary much more widely in
      size than the Oviraptoridae.

PMID- 29567955
TI  - Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in
      locusts.
AB  - Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the
      mechanism by which Dop1 modulates this process remains unknown to date. Here, we
      identify differentially expressed small RNAs associated with locust olfactory
      attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis
      and qPCR validation reveal that Dop1 activation and inhibition downregulates and
      upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in
      solitarious locusts increases their attraction to gregarious volatiles, whereas
      miR-9a overexpression in gregarious locusts reduces olfactory attraction.
      Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its
      downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates
      locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression
      through inducing the dissociation of La protein from pre-miR-9a and resulting in
      miR-9a maturation inhibition. Our results reveal a Dop1-miR-9a-AC2 circuit that
      modulates locust olfactory attraction underlying aggregation. This study suggests
      that miRNAs act as key messengers in the GPCR signaling.

PMID- 29567956
TI  - The molecular mechanism for activating IgA production by Pediococcus acidilactici
      K15 and the clinical impact in a randomized trial.
AB  - IgA secretion at mucosal sites is important for host defence against pathogens as
      well as maintaining the symbiosis with microorganisms present in the small
      intestine that affect IgA production. In the present study, we tested the ability
      of 5 strains of lactic acid bacteria stimulating IgA production, being
      Pediococcus acidilactici K15 selected as the most effective on inducing this
      protective immunoglobulin. We found that this response was mainly induced via IL
      10, as efficiently as IL-6, secreted by K15-stimulated dendritic cells.
      Furthermore, bacterial RNA was largely responsible for the induction of these
      cytokines; double-stranded RNA was a major causative molecule for IL-6 production
      whereas single-stranded RNA was critical factor for IL-10 production. In a
      randomized, double-blind, placebo-controlled clinical trial, ingestion of K15
      significantly increased the secretory IgA (sIgA) concentration in saliva compared
      with the basal level observed before this intervention. These results indicate
      that functional lactic acid bacteria induce IL-6 and IL-10 production by
      dendritic cells, which contribute to upregulating the sIgA concentration at
      mucosal sites in humans.

PMID- 29567957
TI  - Cryo-EM structure of human mTOR complex 2.
AB  - Mechanistic target of rapamycin (mTOR) complex 2 (mTORC2) plays an essential role
      in regulating cell proliferation through phosphorylating AGC protein kinase
      family members, including AKT, PKC and SGK1. The functional core complex consists
      of mTOR, mLST8, and two mTORC2-specific components, Rictor and mSin1. Here we
      investigated the intermolecular interactions within mTORC2 complex and determined
      its cryo-electron microscopy structure at 4.9 A resolution. The structure reveals
      a hollow rhombohedral fold with a 2-fold symmetry. The dimerized mTOR serves as a
      scaffold for the complex assembly. The N-terminal half of Rictor is composed of
      helical repeat clusters and binds to mTOR through multiple contacts. mSin1 is
      located close to the FRB domain and catalytic cavity of mTOR. Rictor and mSin1
      together generate steric hindrance to inhibit binding of FKBP12-rapamycin to
      mTOR, revealing the mechanism for rapamycin insensitivity of mTORC2. The mTOR
      dimer in mTORC2 shows more compact conformation than that of mTORC1 (rapamycin
      sensitive), which might result from the interaction between mTOR and Rictor
      mSin1. Structural comparison shows that binding of Rictor and Raptor (mTORC1
      specific component) to mTOR is mutually exclusive. Our study provides a basis for
      understanding the assembly of mTORC2 and a framework to further characterize the
      regulatory mechanism of mTORC2 pathway.

PMID- 29567958
TI  - PHA-4/FoxA senses nucleolar stress to regulate lipid accumulation in
      Caenorhabditis elegans.
AB  - The primary function of the nucleolus is ribosome biogenesis, which is an
      extremely energetically expensive process. Failures in ribosome biogenesis cause
      nucleolar stress with an altered energy status. However, little is known about
      the underlying mechanism linking nucleolar stress to energy metabolism. Here we
      show that nucleolar stress is triggered by inactivation of RSKS-1 (ribosomal
      protein S6 kinase), RRP-8 (ribosomal RNA processing 8), and PRO-2/3 (proximal
      proliferation), all of which are involved in ribosomal RNA processing or
      inhibition of rDNA transcription by actinomycin D (AD), leading to excessive
      lipid accumulation in Caenorhabditis elegans. The transcription factor PHA-4/FoxA
      acts as a sensor of nucleolar stress to bind to and transactivate the expression
      of the lipogenic genes pod-2 (acetyl-CoA carboxylase), fasn-1 (fatty acid
      synthase), and dgat-2 (diacylglycerol O-acyltransferase 2), consequently
      promoting lipid accumulation. Importantly, inactivation of pha-4 or dgat-2 is
      sufficient to abolish nucleolar stress-induced lipid accumulation and prolonged
      starvation survival. The results revealed a distinct PHA-4-mediated lipogenesis
      pathway that senses nucleolar stress and shifts excessive energy for storage as
      fat.

PMID- 29567959
TI  - HIV-exposure, early life feeding practices and delivery mode impacts on faecal
      bacterial profiles in a South African birth cohort.
AB  - There are limited data on meconium and faecal bacterial profiles from African
      infants and their mothers. We characterized faecal bacterial communities of
      infants and mothers participating in a South African birth cohort. Stool and
      meconium specimens were collected from 90 mothers and 107 infants at birth, and
      from a subset of 72 and 36 infants at 4-12 and 20-28 weeks of age, respectively.
      HIV-unexposed infants were primarily exclusively breastfed at 4-12 (49%, 26/53)
      and 20-28 weeks (62%, 16/26). In contrast, HIV-exposed infants were primarily
      exclusively formula fed at 4-12 (53%; 10/19) and 20-28 weeks (70%, 7/10).
      Analysis (of the bacterial 16S rRNA gene sequences of the V4 hypervariable
      region) of the 90 mother-infant pairs showed that meconium bacterial profiles
      [dominated by Proteobacteria (89%)] were distinct from those of maternal faeces
      [dominated by Firmicutes (66%) and Actinobacteria (15%)]. Actinobacteria
      predominated at 4-12 (65%) and 20-28 (50%) weeks. HIV-exposed infants had
      significantly higher faecal bacterial diversities at both 4-12 (p = 0.026) and 20
      28 weeks (p = 0.002). HIV-exposed infants had lower proportions of
      Bifidobacterium (p = 0.010) at 4-12 weeks. Maternal faecal bacterial profiles
      were influenced by HIV status, feeding practices and mode of delivery. Further
      longitudinal studies are required to better understand how these variables
      influence infant and maternal faecal bacterial composition.

PMID- 29567960
TI  - Isolation of diborenes and their 90 degrees -twisted diradical congeners.
AB  - Molecules containing multiple bonds between atoms-most often in the form of
      olefins-are ubiquitous in nature, commerce, and science, and as such have a huge
      impact on everyday life. Given their prominence, over the last few decades,
      frequent attempts have been made to perturb the structure and reactivity of
      multiply-bound species through bending and twisting. However, only modest success
      has been achieved in the quest to completely twist double bonds in order to
      homolytically cleave the associated pi bond. Here, we present the isolation of
      double-bond-containing species based on boron, as well as their fully twisted
      diradical congeners, by the incorporation of attached groups with different
      electronic properties. The compounds comprise a structurally authenticated set of
      diamagnetic multiply-bound and diradical singly-bound congeners of the same class
      of compound.

PMID- 29567961
TI  - Rac1 in podocytes promotes glomerular repair and limits the formation of
      sclerosis.
AB  - Rac1, a Rho family member, is ubiquitously expressed and participates in various
      biological processes. Rac1 expression is induced early in podocyte injury, but
      its role in repair is unclear. To investigate the role of Rac1 expression in
      podocytes under pathological conditions, we used podocyte-specific Rac1
      conditional knock-out (cKO) mice administered adriamycin (ADR), which causes
      nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more
      adhesion of the GBM to Bowman's capsule, and a higher ratio of sclerotic
      glomeruli were observed in Rac1 cKO mice than in control mice, whereas no
      differences were observed in glomerular podocyte numbers in both groups after ADR
      treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the
      cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in
      those of control mice under pathological conditions. In accordance with this
      result, the volumes of podocytes in Rac1 cKO mice were significantly reduced
      compared with those of control mice. Experiments using in vitro ADR-administered
      Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR
      activity in injured podocytes. Taken together, these data indicate that Rac1
      associated mTOR activation in podocytes plays an important role in preventing the
      kidneys from developing glomerulosclerosis.

PMID- 29567963
TI  - Intramolecular 13C analysis of tree rings provides multiple plant ecophysiology
      signals covering decades.
AB  - Measurements of carbon isotope contents of plant organic matter provide important
      information in diverse fields such as plant breeding, ecophysiology,
      biogeochemistry and paleoclimatology. They are currently based on 13C/12C ratios
      of specific, whole metabolites, but we show here that intramolecular ratios
      provide higher resolution information. In the glucose units of tree-ring
      cellulose of 12 tree species, we detected large differences in 13C/12C ratios
      (>100/00) among carbon atoms, which provide isotopically distinct inputs to major
      global C pools, including wood and soil organic matter. Thus, considering
      position-specific differences can improve characterisation of soil-to-atmosphere
      carbon fluxes and soil metabolism. In a Pinus nigra tree-ring archive formed from
      1961 to 1995, we found novel 13C signals, and show that intramolecular analysis
      enables more comprehensive and precise signal extraction from tree rings, and
      thus higher resolution reconstruction of plants' responses to climate change.
      Moreover, we propose an ecophysiological mechanism for the introduction of a 13C
      signal, which links an environmental shift to the triggered metabolic shift and
      its intramolecular 13C signature. In conclusion, intramolecular 13C analyses can
      provide valuable new information about long-term metabolic dynamics for numerous
      applications.

PMID- 29567962
TI  - Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.
AB  - PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is
      involved in the sour sensation and other pH-dependent processes. PKD2L1 is
      believed to be a nonselective cation channel that can be regulated by voltage,
      protons, and calcium. Despite its considerable importance, the molecular
      mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine
      the PKD2L1 atomic structure at 3.38 A resolution by cryo-electron microscopy,
      whereby side chains of nearly all residues are assigned. Unlike its ortholog
      PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are
      involved in upper and lower-gate opening, adopt an open conformation. Structural
      comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore
      domain dilation is coupled to conformational changes of voltage-sensing domains
      (VSDs) via a series of pi-pi interactions, suggesting a potential PKD2L1 gating
      mechanism.

PMID- 29567964
TI  - Diffuse Myocardial Injuries are Present in Subclinical Hypothyroidism: A Clinical
      Study Using Myocardial T1-mapping Quantification.
AB  - Subclinical hypothyroidism (SHT) is a common disorder that may represent early
      thyroid dysfunction and is related to adverse cardiovascular events. However,
      myocardial injuries induced by SHT are difficult to detect. Our previous study
      demonstrated that the cardiac magnetic resonance (CMR) myocardial longitudinal
      relaxation time (T1) mapping technique is a useful tool for assessing diffuse
      myocardial injuries in overt hypothyroidism patients. This study was designed to
      detect whether diffuse myocardial injuries were present in SHT by using the T1
      mapping technique. We found that SHT participants had significantly increased
      native T1 values within four segments of the left ventricle (all p < 0.01),
      especially patients with thyroid-stimulating hormone (TSH) levels >=10 uIU/mL,
      compared with those in the controls. In addition, the native T1 values were
      negatively correlated with free thyroxine (FT4) (r = -0.476, p = 0.003) and were
      positively correlated with TSH (r = 0.489, p = 0.002). Furthermore, left
      ventricular diastolic function estimated by the peak filling rate (PFR) was
      significantly lower in patients with TSH levels >=10 uIU/mL than that in the
      controls (p < 0.05). In conclusion, diffuse myocardial injuries were present in
      SHT, and T1 mapping may be a useful tool for evaluating mild myocardial injuries
      in SHT at an early stage. Our study is the first to confirm myocardial injuries
      in SHT patients using T1 mapping.

PMID- 29567965
TI  - Atomistic scale investigation of cation ordering and phase stability in Cs
      substituted Ba1.33Zn1.33Ti6.67O16, Ba1.33Ga2.66Ti5.67O16 and
      Ba1.33Al2.66Ti5.33O16 hollandite.
AB  - The titanate-based hollandite structure is proposed as an effective ceramic waste
      form for Cs-immobilization. In this study, quantum-mechanical calculations were
      used to quantify the impact of A-site and B-site ordering on the structural
      stability of hollandite with compositions BaxCsy(MzTi8-z)O16, where M = Zn2+,
      Ga3+, and Al3+. The calculated enthalpy of formation agrees with experimental
      measurements of related hollandite phases from melt solution calorimetry. Ground
      state geometry optimizations show that, for intermediate compositions (e.g.,
      CsBaGa6Ti18O48), the presence of both Cs and Ba in the A-site tunnels is not
      energetically favored. However, the decay heat generated during storage of the Cs
      containing waste form may overcome the energetics of Ba and Cs mixing in the
      tunnel structure of hollandite. The ability of the hollandite structure to
      accommodate the radioparagenesis of Cs to Ba is critical for long term
      performance of the waste. For the first time, B-site ordering was observed along
      the tunnel direction ([001] zone axis) for the Ga-hollandite compositions, as
      well as the intermediate Al-hollandite composition. These compositionally
      dependent structural features, and associated formation enthalpies, are of
      importance to the stability and radiation damage tolerance of ceramic waste
      forms.

PMID- 29567967
TI  - Publisher Correction: Ultrafast quantum beats of anisotropic excitons in
      atomically thin ReS2.
AB  - In the originally published HTML and PDF versions of this article, Figs. 3g and
      4d contained typesetting errors affecting the way the data points were displayed.
      This has now been corrected in the HTML and PDF versions.

PMID- 29567966
TI  - Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids
      reduces chronic alcohol intake and abolishes binge-drinking.
AB  - Chronic alcohol intake leads to neuroinflammation and astrocyte dysfunction,
      proposed to perpetuate alcohol consumption and to promote conditioned relapse
      like binge drinking. In the present study, human mesenchymal stem cells (MSCs)
      were cultured in 3D-conditions to generate MSC-spheroids, which greatly increased
      MSCs anti-inflammatory ability and reduced cell volume by 90% versus
      conventionally 2D-cultured MSCs, enabling their intravenous administration and
      access to the brain. It is shown, in an animal model of chronic ethanol intake
      and relapse-drinking, that both the intravenous and intra-cerebroventricular
      administration of a single dose of MSC-spheroids inhibited chronic ethanol intake
      and relapse-like drinking by 80-90%, displaying significant effects over 3-5
      weeks. The MSC-spheroid administration fully normalized alcohol-induced
      neuroinflammation, as shown by a reduced astrocyte activation, and markedly
      increased the levels of the astrocyte Na-glutamate (GLT-1) transporter. This
      research suggests that the intravenous administration of MSC-spheroids may
      constitute an effective new approach for the treatment of alcohol-use disorders.

PMID- 29567968
TI  - Coherent all-optical transistor based on frustrated total internal reflection.
AB  - This study aims to design an all-optical transistor based on tunneling of light
      through frustrated total internal reflection. Under total internal reflection,
      the electromagnetic wave penetrates into the lower index medium. If a medium with
      high refractive index is placed close to the boundary of the first one, a portion
      of light leaks into the second medium. The penetrated electromagnetic field
      distribution can be influenced by another coherent light in the low refractive
      index medium via interference, leading to light amplification. Upon this
      technique, we introduce coherent all-optical transistors based on photonic
      crystal structures. Subsequently, we inspect the shortest pulse which is
      amplified by the designed system and also its terahertz repetition rate. We will
      show that such a system can operate in a cascade form. Operating in terahertz
      range and the amplification efficiency of around 20 are of advantages of this
      system.

PMID- 29567969
TI  - Fast first-photon ghost imaging.
AB  - Conventional imaging at low light levels requires hundreds of detected photons
      per pixel to suppress the Poisson noise for accurate reflectivity inference. We
      propose a high-efficiency photon-limited imaging technique, called fast first
      photon ghost imaging, which recovers the image by conditional averaging of the
      reference patterns selected by the first-photon detection signal. Our technique
      merges the physics of low-flux measurements with the framework of computational
      ghost imaging. Experimental results demonstrate that it can reconstruct an image
      from less than 0.1 detected photon per pixel, which is three orders of magnitude
      less than conventional imaging techniques. A signal-to-noise ratio model of the
      system is established for noise analysis. With less data manipulation and shorter
      time requirements, our technique has potential applications in many fields,
      ranging from biological microscopy to remote sensing.

PMID- 29567970
TI  - Data-based Decision Rules to Personalize Depression Follow-up.
AB  - Depression is a common mental illness with complex and heterogeneous progression
      dynamics. Risk grouping of depression treatment population based on their
      longitudinal patterns has the potential to enable cost-effective monitoring
      policy design. This paper establishes a rule-based method to identify a set of
      risk predictive patterns from person-level longitudinal disease measurements by
      integrating the data transformation, rule discovery and rule evaluation. We
      further extend the identified rules to create rule-based monitoring strategies to
      adaptively monitor individuals with different disease severities. We applied the
      rule-based method on an electronic health record (EHR) dataset of depression
      treatment population containing person-level longitudinal Patient Health
      Questionnaire (PHQ)-9 scores for assessing depression severity. 12 risk
      predictive rules are identified, and the rule-based prognostic model based on
      identified rules enables more accurate prediction of disease severity than other
      prognostic models including RuleFit, logistic regression and Support Vector
      Machine. Two rule-based monitoring strategies outperform the latest PHQ-9 based
      monitoring strategy by providing higher sensitivity and specificity. The rule
      based method can lead to a better understanding of disease dynamics, achieving
      more accurate prognostics of disease progressions, personalizing follow-up
      intervals, and designing cost-effective monitoring of patients in clinical
      practice.

PMID- 29567972
TI  - Author Correction: Fast modal decomposition for optical fibers using digital
      holography.
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- 29567971
TI  - Molecular basis of binding between the global post-transcriptional regulator CsrA
      and the T3SS chaperone CesT.
AB  - The T3SS chaperone CesT is recently shown to interact with the post
      transcriptional regulator CsrA to modulate post-attachment signaling in
      enteropathogenic and enterohemorrhagic Escherichia coli. The molecular basis of
      the CesT/CsrA binding, however, remains elusive. Here, we show that CesT and CsrA
      both created two ligand binding sites in their homodimers, forming irregular
      multimeric complexes in solution. Through construction of a recombinant CsrA
      dimer (Re-CsrA) that contains a single CesT binding site, the atomic binding
      features between CesT and CsrA are delineated via the structure of the CesT/Re
      CsrA complex. In contrast to a previously reported N-terminally swapped dimer
      form, CesT adopts a dimeric architecture with a swapped C-terminal helix for CsrA
      engagement. In CsrA, CesT binds to a surface patch that extensively overlaps with
      its mRNA binding site. The binding mode therefore justifies a mechanism of CsrA
      modulation by CesT via competitive inhibition of the CsrA/mRNA interactions.

PMID- 29567973
TI  - Author Correction: Highly-sensitive capture of circulating tumor cells using
      micro-ellipse filters.
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- 29567974
TI  - Publisher Correction: Four dimensional material movies: High speed phase-contrast
      tomography by backprojection along dynamically curved paths.
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- 29567975
TI  - Loss of IDH2 Accelerates Age-related Hearing Loss in Male Mice.
AB  - Isocitrate dehydrogenase (IDH) 2 participates in the TCA cycle and catalyzes the
      conversion of isocitrate to alpha-ketoglutarate and NADP+ to NADPH. In the
      mitochondria, IDH2 also plays a key role in protecting mitochondrial components
      from oxidative stress by supplying NADPH to both glutathione reductase (GSR) and
      thioredoxin reductase 2 (TXNRD2). Here, we report that loss of Idh2 accelerates
      age-related hearing loss, the most common form of hearing impairment, in male
      mice. This was accompanied by increased oxidative DNA damage, increased apoptotic
      cell death, and profound loss of spiral ganglion neurons and hair cells in the
      cochlea of 24-month-old Idh2-/- mice. In young male mice, loss of Idh2 resulted
      in decreased NADPH redox state and decreased activity of TXNRD2 in the
      mitochondria of the inner ear. In HEI-OC1 mouse inner ear cell lines, knockdown
      of Idh2 resulted in a decline in cell viability and mitochondrial oxygen
      consumption. This was accompanied by decreased NADPH redox state and decreased
      activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2
      functions as the principal source of NADPH for the mitochondrial thioredoxin
      antioxidant defense and plays an essential role in protecting hair cells and
      neurons against oxidative stress in the cochlea of male mice.

PMID- 29567976
TI  - SpliceDetector: a software for detection of alternative splicing events in human
      and model organisms directly from transcript IDs.
AB  - In eukaryotes, different combinations of exons lead to multiple transcripts with
      various functions in protein level, in a process called alternative splicing
      (AS). Unfolding the complexity of functional genomics through genome-wide
      profiling of AS and determining the altered ultimate products provide new
      insights for better understanding of many biological processes, disease progress
      as well as drug development programs to target harmful splicing variants. The
      current available tools of alternative splicing work with raw data and include
      heavy computation. In particular, there is a shortcoming in tools to discover AS
      events directly from transcripts. Here, we developed a Windows-based user
      friendly tool for identifying AS events from transcripts without the need to any
      advanced computer skill or database download. Meanwhile, due to online working
      mode, our application employs the updated SpliceGraphs without the need to any
      resource updating. First, SpliceGraph forms based on the frequency of active
      splice sites in pre-mRNA. Then, the presented approach compares query transcript
      exons to SpliceGraph exons. The tool provides the possibility of statistical
      analysis of AS events as well as AS visualization compared to SpliceGraph. The
      developed application works for transcript sets in human and model organisms.

PMID- 29567977
TI  - Magnetic field effect on the energy levels of an exciton in a GaAs quantum dot:
      Application for excitonic lasers.
AB  - The problem of an exciton trapped in a Gaussian quantum dot (QD) of GaAs is
      studied in both two and three dimensions in the presence of an external magnetic
      field using the Ritz variational method, the 1/N expansion method and the shifted
      1/N expansion method. The ground state energy and the binding energy of the
      exciton are obtained as a function of the quantum dot size, confinement strength
      and the magnetic field and compared with those available in the literature. While
      the variational method gives the upper bound to the ground state energy, the 1/N
      expansion method gives the lower bound. The results obtained from the shifted 1/N
      expansion method are shown to match very well with those obtained from the exact
      diagonalization technique. The variation of the exciton size and the oscillator
      strength of the exciton are also studied as a function of the size of the quantum
      dot. The excited states of the exciton are computed using the shifted 1/N
      expansion method and it is suggested that a given number of stable excitonic
      bound states can be realized in a quantum dot by tuning the quantum dot
      parameters. This can open up the possibility of having quantum dot lasers using
      excitonic states.

PMID- 29567978
TI  - Conical Refraction Bottle Beams for Entrapment of Absorbing Droplets.
AB  - Conical refraction (CR) optical bottle beams for photophoretic trapping of
      airborne absorbing droplets are introduced and experimentally demonstrated. CR
      describes the circular split-up of unpolarised light propagating along an optical
      axis in a biaxial crystal. The diverging and converging cones lend themselves to
      the construction of optical bottle beams with flexible entry points. The
      interaction of single inkjet droplets with an open or partly open bottle beam is
      shown implementing high-speed video microscopy in a dual-view configuration.
      Perpendicular image planes are visualized on a single camera chip to characterize
      the integral three-dimensional movement dynamics of droplets. We demonstrate how
      a partly opened optical bottle transversely confines liquid objects. Furthermore
      we observe and analyse transverse oscillations of absorbing droplets as they hit
      the inner walls and simultaneously measure both transverse and axial velocity
      components.

PMID- 29567979
TI  - Kinematic features in patients with lateral discoid meniscus injury during
      walking.
AB  - At present, there few studies on the kinematic features of lateral discoid
      meniscus injury. In this study, a motion capture system was used to investigate
      the motion characteristics of knees with lateral discoid meniscus after injury,
      and the differences between the knees with lateral meniscus and intact knees were
      compared. Fourteen patients diagnosed with unilateral lateral discoid meniscus
      injury, fourteen patients diagnosed with unilateral lateral meniscus injury, and
      fourteen normal subjects with healthy knees were recruited and grouped. Through
      kinematic gait analysis, it was found that the subjects in the two groups with
      meniscus injuries exhibited significantly smaller ranges of rotation and
      translation than those with healthy knees on the sagittal, coronal, and
      horizontal planes, but not in proximal-distal translation. Maximum lateral tibial
      translation and maximum internal tibial rotation in the knees with lateral
      discoid meniscus injury were significantly decreased compared to those with
      lateral meniscus injury. The results show that the kinematic features of knees
      with lateral discoid meniscus injury are statistically different than those of
      healthy knees and knees with lateral meniscus injury. This study provides an
      important reference for the dynamic function of knees with lateral discoid
      meniscus injury.

PMID- 29567980
TI  - Author Correction: Association of wall shear stress with intracranial aneurysm
      rupture: systematic review and meta-analysis.
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- 29567981
TI  - Population attributable fractions continue to unmask the power of prevention.
AB  - The population attributable fraction is a critical driver of evidence-based
      cancer prevention. With an increasing recognition of the need for high-level
      investment in cancer control, there is an overwhelming need for a new generation
      of descriptive studies that globally promote the long-term public health and
      economic benefits of cancer prevention.

PMID- 29567982
TI  - The fraction of cancer attributable to modifiable risk factors in England, Wales,
      Scotland, Northern Ireland, and the United Kingdom in 2015.
AB  - BACKGROUND: Changing population-level exposure to modifiable risk factors is a
      key driver of changing cancer incidence. Understanding these changes is therefore
      vital when prioritising risk-reduction policies, in order to have the biggest
      impact on reducing cancer incidence. UK figures on the number of risk factor
      attributable cancers are updated here to reflect changing behaviour as assessed
      in representative national surveys, and new epidemiological evidence. Figures are
      also presented by UK constituent country because prevalence of risk factor
      exposure varies between them. METHODS: Population attributable fractions (PAFs)
      were calculated for combinations of risk factor and cancer type with
      sufficient/convincing evidence of a causal association. Relative risks (RRs) were
      drawn from meta-analyses of cohort studies where possible. Prevalence of exposure
      to risk factors was obtained from nationally representative population surveys.
      Cancer incidence data for 2015 were sourced from national data releases and,
      where needed, personal communications. PAF calculations were stratified by age,
      sex and risk factor exposure level and then combined to create summary PAFs by
      cancer type, sex and country. RESULTS: Nearly four in ten (37.7%) cancer cases in
      2015 in the UK were attributable to known risk factors. The proportion was around
      two percentage points higher in UK males (38.6%) than in UK females (36.8%).
      Comparing UK countries, the attributable proportion was highest in Scotland
      (41.5% for persons) and lowest in England (37.3% for persons). Tobacco smoking
      contributed by far the largest proportion of attributable cancer cases, followed
      by overweight/obesity, accounting for 15.1% and 6.3%, respectively, of all cases
      in the UK in 2015. For 10 cancer types, including two of the five most common
      cancer types in the UK (lung cancer and melanoma skin cancer), more than 70% of
      UK cancer cases were attributable to known risk factors. CONCLUSION: Tobacco and
      overweight/obesity remain the top contributors of attributable cancer cases.
      Tobacco smoking has the highest PAF because it greatly increases cancer risk and
      has a large number of cancer types associated with it. Overweight/obesity has the
      second-highest PAF because it affects a high proportion of the UK population and
      is also linked with many cancer types. Public health policy may seek to mitigate
      the level of harm associated with exposure or reduce exposure levels-both
      approaches may effectively impact cancer incidence. Differences in PAFs between
      countries and sexes are primarily due to varying prevalence of exposure to risk
      factors and varying proportions of specific cancer types. This variation in turn
      is affected by socio-demographic differences which drive differences in exposure
      to theoretically avoidable 'lifestyle' factors. PAFs at UK country level have not
      been available previously and they should be used by policymakers in devolved
      nations. PAFs are estimates based on the best available data, limitations in
      those data would generally bias toward underestimation of PAFs. Regular
      collection of risk factor exposure prevalence data which corresponds with
      epidemiological evidence is vital for analyses like this and should remain a
      priority for the UK Government and devolved Administrations.

PMID- 29567983
TI  - Author Correction: Toxic fluoride gas emissions from lithium-ion battery fires.
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- 29567984
TI  - Genetic homogeneity of the invasive lionfish across the Northwestern Atlantic and
      the Gulf of Mexico based on Single Nucleotide Polymorphisms.
AB  - Despite the devastating impact of the lionfish (Pterois volitans) invasion on NW
      Atlantic ecosystems, little genetic information about the invasion process is
      available. We applied Genotyping by Sequencing techniques to identify 1,220
      single nucleotide polymorphic sites (SNPs) from 162 lionfish samples collected
      between 2013 and 2015 from two areas chronologically identified as the first and
      last invaded areas in US waters: the east coast of Florida and the Gulf of
      Mexico. We used population genomic analyses, including phylogenetic
      reconstruction, Bayesian clustering, genetic distances, Discriminant Analyses of
      Principal Components, and coalescence simulations for detection of outlier SNPs,
      to understand genetic trends relevant to the lionfish's long-term persistence. We
      found no significant differences in genetic structure or diversity between the
      two areas (FST p-values > 0.01, and t-test p-values > 0.05). In fact, our genomic
      analyses showed genetic homogeneity, with enough gene flow between the east coast
      of Florida and Gulf of Mexico to erase previous signals of genetic divergence
      detected between these areas, secondary spreading, and bottlenecks in the Gulf of
      Mexico. These findings suggest rapid genetic changes over space and time during
      the invasion, resulting in one panmictic population with no signs of divergence
      between areas due to local adaptation.

PMID- 29567986
TI  - Diverse Assemblage of Ediacaran fossils from Central Iran.
AB  - Reinvestigation of the Kushk and Chahmir areas (Bafq and Behabad regions) of
      central Iran has yielded a diverse assemblage of Ediacaran fossils, including
      several new species, just prior to the Cambrian explosion of complex animals. The
      Kushk series consists mainly of shallow marine carbonate deposits followed by
      deep-water calcareous marine shales. Ediacaran fossils occur commonly in the
      shale deposits and include biostratigraphically-important taxa Cloudina and
      Corumbella, which confirms a latest Ediacaran age for these deposits, the
      youngest examples of Kimberellomorphs (stem-group molluscs) that helps bridge the
      gap between their first occurrence in the middle-Ediacaran and the crown
      diversification in the Cambrian, and likely sponges, which are rare prior to the
      Cambrian.

PMID- 29567985
TI  - Trends in stroke subtypes and vascular risk factors in a stroke center in China
      over 10 years.
AB  - Rapid economic development in China has caused marked changes in people's
      lifestyles and medical technology. Exploration of stroke subtype trends is
      necessary to provide physicians with vital insight for early diagnosis and
      treatment. We included stroke patients admitted from 2006 to 2015. Trends in
      stroke subtypes and vascular risk factors were investigated. There were 5521
      patients, including 4534 (82.1%) ischemic stroke (IS), 813 (14.7%) intracerebral
      hemorrhage (ICH) and 174 (3.2%) subarachnoid hemorrhage (SAH) patients. The
      proportion of IS was increasing and proportions of ICH and SAH were decreasing (P
      < 0.001). Onset age and hypertension remained stable in stroke subtypes. In IS
      patients, large artery atherosclerosis (LAA) strokes increased from 17.0% to
      30.8% in the first 7 years and ultimately decreased to 24.1%. Small vessel
      disease (SVD) strokes increased from 15.5% to 39.6%, undetermined etiology (UE)
      strokes decreased from 52.7% to 26.0%, others remained stable. The levels of low
      density lipoprotein declined significantly, and an increased number of patients
      underwent intracranial artery examinations (P < 0.001). In conclusion,
      proportions of stroke subtypes changed significantly. Anti-hypertension therapy
      needs to be reinforced to control ICH, SAH and SVD ischemic stroke incidences.
      The etiologic detection of IS increased and lipid-lowing therapy was effective,
      cardioembolism detections should be reinforced.

PMID- 29567988
TI  - Author Correction: Interferometric rotating point spread function.
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- 29567987
TI  - Tumor-associated macrophages-derived exosomes promote the migration of gastric
      cancer cells by transfer of functional Apolipoprotein E.
AB  - Tumor-associated macrophages (TAMs) are a major component of the tumor
      microenvironment and have been shown to contribute to tumor aggressiveness.
      However, the detailed mechanisms underlying the pro-metastatic effect of TAMs on
      gastric cancer are not clearly defined. Here, we show that TAMs are enriched in
      gastric cancer. TAMs are characterized by M2-polarized phenotype and promote
      migration of gastric cancer cells in vitro and in vivo. Furthermore, we find that
      M2-derived exosomes determine the TAMs-mediated pro-migratory activity. Using
      mass spectrometry, we identify that apolipoprotein E (ApoE) is highly specific
      and effective protein in M2 macrophages-derived exosomes. Moreover, TAMs are
      uniquely immune cells population expressed ApoE in gastric cancer
      microenvironment. However, exosomes derived from M2 macrophages of Apoe -/- mice
      have no significant effect on the migration of gastric cancer cells in vitro and
      in vivo. Mechanistically, M2 macrophage-derived exosomes mediate an intercellular
      transfer of ApoE-activating PI3K-Akt signaling pathway in recipient gastric
      cancer cells to remodel the cytoskeleton-supporting migration. Collectively, our
      findings signify that the exosome-mediated transfer of functional ApoE protein
      from TAMs to the tumor cells promotes the migration of gastric cancer cells.

PMID- 29567989
TI  - Asymmetric synthesis of gamma-branched amines via rhodium-catalyzed reductive
      amination.
AB  - Amines bearing gamma-stereocenters are highly important structural motifs in many
      biologically active compounds. However, reported enantioselective syntheses of
      these molecules are indirect and often require multiple steps. Herein, we report
      a general asymmetric route for the one-pot synthesis of chiral gamma-branched
      amines through the highly enantioselective isomerization of allylamines, followed
      by enamine exchange and subsequent chemoselective reduction. This protocol is
      suitable for establishing various tertiary stereocenters, including those
      containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl
      substituents, which allows for a rapid and modular synthesis of many chiral gamma
      branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine
      are synthesized using this method with high levels of enantioselectivity.

PMID- 29567990
TI  - Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal
      squamous cell carcinoma.
AB  - Although many articles have uncovered that Wnt signaling is involved in
      radioresistance, the mechanism is rarely reported. Here we generated two
      radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells
      ECA109 and Kyse150. We then found that Wnt signaling activity was higher in
      radioresistant cells and was further activated upon ionizing radiation (IR)
      exposure. In addition, radioresistant cells acquired epithelial-to-mesenchymal
      transition (EMT) properties and stem quality. Wnt signaling was then found to be
      involved in radioresistance by promoting DNA damage repair. In our present study,
      high-mobility group box 1 protein (HMGB1), a chromatin-associated protein, was
      firstly found to be transactivated by Wnt signaling and mediate Wnt-induced
      radioresistance. The role of HMGB1 in the regulation of DNA damage repair with
      the activation of DNA damage checkpoint response in response to IR was the main
      cause of HMGB1-induced radioresistance.

PMID- 29567991
TI  - BEARscc determines robustness of single-cell clusters using simulated technical
      replicates.
AB  - Single-cell messenger RNA sequencing (scRNA-seq) has emerged as a powerful tool
      to study cellular heterogeneity within complex tissues. Subpopulations of cells
      with common gene expression profiles can be identified by applying unsupervised
      clustering algorithms. However, technical variance is a major confounding factor
      in scRNA-seq, not least because it is not possible to replicate measurements on
      the same cell. Here, we present BEARscc, a tool that uses RNA spike-in controls
      to simulate experiment-specific technical replicates. BEARscc works with a wide
      range of existing clustering algorithms to assess the robustness of clusters to
      technical variation. We demonstrate that the tool improves the unsupervised
      classification of cells and facilitates the biological interpretation of single
      cell RNA-seq experiments.

PMID- 29567992
TI  - Crotamine induces browning of adipose tissue and increases energy expenditure in
      mice.
AB  - Crotamine, originally isolated from rattlesnake venom, has been extensively
      studied due to its pleiotropic biological properties, and special attention has
      been paid to its antitumor activity. However, long-term treatment with crotamine
      was accompanied by a reduction in animal body weight gain and by increases in
      glucose tolerance. As cancer is commonly associated with cachexia, to preclude
      the possible cancer cachexia-like effect of crotamine, herein this polypeptide
      was administered in healthy wild-type C57/BL6 mice by the oral route daily, for
      21 days. Reduced body weight gain, in addition to decreased white adipose tissue
      (WAT) and increased brown adipose tissue (BAT) mass were observed in healthy
      animals in the absence of tumor. In addition, we observed improved glucose
      tolerance and increased insulin sensitivity, accompanied by a reduction of plasma
      lipid levels and decreased levels of biomarkers of liver damage and kidney
      disfunctions. Importantly, long-term treatment with crotamine increased the basal
      metabolic rate in vivo, which was consistent with the increased expression of
      thermogenic markers in BAT and WAT. Interestingly, cultured brown adipocyte cells
      induced to differentiation in the presence of crotamine also showed increases in
      some of these markers and in lipid droplets number and size, indicating increased
      brown adipocyte maturation.

PMID- 29567993
TI  - Unexplored therapeutic opportunities in the human genome.
AB  - This corrects the article DOI: 10.1038/nrd.2018.14.

PMID- 29567994
TI  - Accelerating the development of therapeutic strategies for drug-resistant
      tuberculosis.
AB  - Recent progress in the discovery, development and evaluation of new drugs and
      combination regimens for drug-resistant tuberculosis through greater
      collaboration between industry, donors and academia provides renewed hope for
      overcoming the challenges in tuberculosis treatment.

PMID- 29567995
TI  - Molecular Camouflage of Plasmodium falciparum Merozoites by Binding of Host
      Vitronectin to P47 Fragment of SERA5.
AB  - The malaria parasite Plasmodium falciparum proliferates in the blood stream where
      the host immune system is most active. To escape from host immunity, P.
      falciparum has developed a number of evasion mechanisms. Serine repeat antigen 5
      (SERA5) is a blood stage antigen highly expressed at late trophozoite and
      schizont stages. The P47 N-terminal domain of SERA5, the basis of SE36 antigen of
      the blood stage vaccine candidate under clinical trials, covers the merozoite
      surface. Exploring the role of the P47 domain, screening of serum proteins showed
      that vitronectin (VTN) directly binds to 20 residues in the C-terminal region of
      SE36. VTN co-localized with P47 domain in the schizont and merozoite stages.
      Phagocytosis assay using THP-1 cells demonstrated that VTN bound to SE36
      prevented engulfment of SE36-beads. In addition, several serum proteins localized
      on the merozoite surface, suggesting that host proteins camouflage merozoites
      against host immunity via binding to VTN.

PMID- 29567996
TI  - Physical and biological roles of mesoscale eddies in Japanese eel larvae
      dispersal in the western North Pacific Ocean.
AB  - The physical and biological roles of mesoscale eddies in Japanese eel larvae
      dispersal are investigated using a three-dimensional (3D) particle-tracking
      method, with a focus on the Subtropical Counter Current eddies of the western
      North Pacific Ocean. Virtual eel larvae (v-larvae) movements depends on the 3D
      ocean currents and active swimming behavior, including vertical swimming (diel
      vertical migration), horizontal directional swimming toward settlement habitat,
      and horizontal swimming toward available food. V-larvae are able to remain in
      eddies passively due to mesoscale eddy nonlinearity and/or actively due to
      attraction to rich food supplies. Thus, both physical trapping and biological
      attraction to food contribute to the retention of v-larvae in eddies. Physical
      trapping dominates the retention of v-larvae whose swimming speeds are slower
      than the eddy propagation speed, whereas biological food attraction prevails in
      the retention of v-larvae swimming faster than eddy propagation. Food
      availability differs between warm (anti-cyclonic) and cold (cyclonic) eddies,
      with the latter providing a richer food supply. Fish larvae that are retained for
      longer durations in cold eddies (shorter durations in warm eddies) are able to
      obtain more food and potentially grow faster, which enhances survival rates.

PMID- 29567997
TI  - Nuclear receptor binding protein 1 correlates with better prognosis and induces
      caspase-dependent intrinsic apoptosis through the JNK signalling pathway in
      colorectal cancer.
AB  - Nuclear receptor binding protein 1 (NRBP1) is a ubiquitously expressed and highly
      conserved pseudokinase that has important roles in cellular homoeostasis. Despite
      recent advances in understanding the biology of NRBP1, the role of NRBP1 and its
      underlying mechanism in colorectal cancer (CRC) have not been fully elucidated.
      In the present study, we observed that NRBP1 expression levels were significantly
      reduced in CRC tissues compared with corresponding adjacent normal tissues, and
      high NRBP1 expression correlated with better prognosis in CRC. Overexpression of
      NRBP1 inhibited CRC cell proliferation and promoted apoptosis in vitro and in
      vivo. In contrast, knockdown of NRBP1 expression increased cell proliferation and
      decreased the percentage of apoptotic cells. Moreover, overexpression of NRBP1
      activated caspase-dependent intrinsic apoptosis. In addition, we further
      discovered that NRBP1 regulated the apoptotic pathway through interaction with
      JNK. Finally, NRBP1 overexpression led to attenuated CRC growth in a xenograft
      mouse model. Our study illustrates the suppressor role of NRBP1 in CRC and
      provides a potential therapeutic target.

PMID- 29567998
TI  - System-wide coordinates of higher order functions in host-pathogen environment
      upon Mycobacterium tuberculosis infection.
AB  - Molecular signatures and their interactions behind the successful establishment
      of infection of Mycobacterium tuberculosis (Mtb) inside macrophage are largely
      unknown. In this work, we present an inter-system scale atlas of the gene
      expression signatures, their interactions and higher order gene functions of
      macrophage-Mtb environment at the time of infection. We have carried out large
      scale meta-analysis of previously published gene expression microarray studies
      andhave identified a ranked list of differentially expressed genes and their
      higher order functions in intracellular Mtb as well as the infected macrophage.
      Comparative analysis of gene expression signatures of intracellular Mtb with the
      in vitro dormant Mtb at different hypoxic and oxidative stress conditions led to
      the identification of the large number of Mtb functional groups, namely operons,
      regulons and pathways that were common and unique to the intracellular
      environment and dormancy state. Some of the functions that are specific to
      intracellular Mtb are cholesterol degradation and biosynthesis of
      immunomodulatory phenolic compounds. The molecular signatures we have identified
      to be involved in adaptation to different stress conditions in macrophage
      environment may be critical for designing therapeutic interventions against
      tuberculosis. And, our approach may be broadly applicable for investigating other
      host-pathogen interactions.

PMID- 29567999
TI  - Operating length and velocity of human vastus lateralis muscle during walking and
      running.
AB  - According to the force-length-velocity relationships, the muscle force potential
      during locomotion is determined by the operating fibre length and velocity. We
      measured fascicle and muscle-tendon unit length and velocity as well as the
      activity of the human vastus lateralis muscle (VL) during walking and running.
      Furthermore, we determined the VL force-length relationship experimentally and
      calculated the force-length and force-velocity potentials (i.e. fraction of
      maximum force according to the force-length-velocity curves) for both gaits.
      During the active state of the stance phase, fascicles showed significantly (p <
      0.05) smaller length changes (walking: 9.2 +/- 4.7% of optimal length (L0);
      running: 9.0 +/- 8.4%L0) and lower velocities (0.46 +/- 0.36 L0/s; 0.03 +/- 0.83
      L0/s) compared to the muscle-tendon unit (walking: 19.7 +/- 5.3%L0, -0.94 +/-
      0.32 L0/s; running: 34.5 +/- 5.8%L0, -2.59 +/- 0.41 L0/s). The VL fascicles
      operated close to optimum length (L0 = 9.4 +/- 0.11 cm) in both walking (8.6 +/-
      0.14 cm) and running (10.1 +/- 0.19 cm), resulting in high force-length (walking:
      0.92 +/- 0.08; running: 0.91 +/- 0.14) and force-velocity (0.91 +/- 0.08; 0.97 +/
      0.13) potentials. For the first time we demonstrated that, in contrast to the
      current general conception, the VL fascicles operate almost isometrically and
      close to L0 during the active state of the stance phase of walking and running.
      The findings further verify an important contribution of the series-elastic
      element to VL fascicle dynamics.

PMID- 29568000
TI  - Are CSNK2A1 gene mutations associated with retinal dystrophy? Report of a patient
      carrier of a novel de novo splice site mutation.

PMID- 29568002
TI  - Application of distribution functions in accurate determination of interdiffusion
      coefficients.
AB  - Diffusion couple technique in combination with the Boltzmann-Matano method is the
      widely used approach to evaluate the interdiffusion coefficients in the target
      systems. However, the quality of the evaluated interdiffusion coefficients due to
      the Boltzmann-Matano method strongly depends on the fitting degree of the
      utilized continuous function to the discrete experimental composition profiles.
      In this paper, the application of different types of distribution functions is
      proposed to solve this problem. For the simple D-c relations, the normal, pseudo
      normal, skew normal, pseudo-skew normal distributions can be employed, while for
      the complex D-c relations, the superposed distributions should be used. Even for
      the cases with uphill diffusion, the combined superposition of distributions may
      be chosen. Through validation in several benchmarks and real alloy systems,
      accurate diffusion coefficients are proved to be successfully obtained by using
      the distribution functions. It is anticipated that the Boltzmann-Matano method
      together with the distribution functions may serve as the general solution for
      determining the accurate interdiffusion coefficients in different materials.

PMID- 29568001
TI  - Dysosteosclerosis is also caused by TNFRSF11A mutation.
AB  - Dysosteosclerosis (DOS) is a form of sclerosing bone disease characterized by
      irregular osteosclerosis and platyspondyly. Its mode of inheritance is autosomal
      recessive. SLC29A3 mutations have been reported as the causal gene in two DOS
      families, however, genetic heterogeneity has been suggested. By whole-exome
      sequencing in a Turkish patient with DOS, we found a novel splice-site mutation
      in TNFRSF11A. TNFRSF11A mutations have previously been reported in two autosomal
      dominant diseases (osteolysis, familial expansile and Paget disease of bone 2,
      early-onset) and an autosomal recessive disease (osteopetrosis, autosomal
      recessive 7). The biallelic mutation, c.616+3A>G, identified in our study was
      located in the splice donor site of intron 6 of TNFRSF11A. Exon trapping assay
      indicated the mutation caused skipping of exon 6, which was predicted to induce a
      frame-shift and an early termination codon in all known alternative transcript
      variants of TNFRSF11A. The predicted effect of the mutation for the isoforms was
      different from those of the previously reported mutations, which could explain
      the difference of their phenotypes. Thus, our study identified the second disease
      gene for DOS. TNFRSF11A isoforms may have the different roles in skeletal
      development and metabolism.

PMID- 29568003
TI  - Whey protein lowers systolic blood pressure and Ca-caseinate reduces serum TAG
      after a high-fat meal in mildly hypertensive adults.
AB  - Epidemiological studies show an inverse association between dairy consumption and
      blood pressure (BP) but there are few data on the postprandial effects of milk
      proteins. This study examined their effects, compared to maltodextrin, on
      postprandial BP and other CVD risk markers in volunteers with mild and pre
      hypertension over an 8 h period. In this double-blinded, randomised, cross-over,
      controlled study 27 adults ingested a high-fat, isoenergetic breakfast and lunch
      with 28 g whey protein, 28 g Ca-caseinate or 27 g maltodextrin. Whey protein
      reduced systolic BP compared with Ca-caseinate (-15.2 +/- 13.6 mmHg) and
      maltodextrin (-23.4 +/- 10.5 mmHg) up to 5 h post-ingestion. There was an
      improvement in arterial stiffness after whey protein compared with maltodextrin
      (incremental Area Under the Curve- iAUC0-8h: +14.4 +/- 6.2%). Despite similar
      glucose levels after both whey protein and Ca-caseinate, whey protein induced a
      higher insulin response than Ca-caseinate (iAUC0-8h: +219.5 +/- 54.6 pmol/L). Ca
      caseinate induced less suppression of non-esterified fatty acids than whey
      protein (iAUC0-5h: -58.9 +/- 135.5 MUmol/L) and maltodextrin (iAUC0-5h: -106.9 +/
      89.4 MUmol/L) and induced a smaller postprandial triacylglycerol response than
      whey protein (iAUC0-8h: -1.68 +/- 0.6 mmol/L). Milk proteins co-ingestion with
      high-fat meals may have the potential to maintain or improve CVD risk factors.

PMID- 29568004
TI  - Author Correction: Ultra-fast Hygrometer based on U-shaped Optical Microfiber
      with Nanoporous Polyelectrolyte Coating.
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- 29568005
TI  - Possible bite-induced abscess and osteomyelitis in Lufengosaurus (Dinosauria:
      sauropodomorph) from the Lower Jurassic of the Yimen Basin, China.
AB  - We report an osseous abnormality on a specimen of the sauropod dinosaur
      Lufengosaurus huenei from the Fengjiahe Formation in Yuxi Basin, China. A gross
      pathological defect occurs on the right third rib, which was subjected to micro
      computed tomographic imaging as an aid in diagnosis. The analysis of pathological
      characteristics and the shape of the abnormality is incompatible with impact or
      healed trauma, such as a common rib fracture, and instead suggests focal
      penetration of the rib, possibly due to a failed predator attack. The
      identification of characteristics based on gross morphology and internal micro
      morphology presented by the specimen, suggests an abscess with osteomyelitis as
      the most parsimonious explanation. Osteomyelitis is a severe infection
      originating in the bone marrow, usually resulting from the introduction of
      pyogenic (pus-producing) bacteria into the bone. Micro-tomographic imaging of the
      lesion suggests a degree of healing and bone remodelling following post-traumatic
      wound infection with evidence of sclerotic bone formation at the site of
      pathological focus, indicating that L. huenei survived the initial trauma.
      However, as osteomyelitis can express through widespread systemic effects,
      including a lowering of immune response and overall condition, this disease may
      have been a contributing factor to the eventual death of the individual.

PMID- 29568006
TI  - Abrupt Climate Change in an Oscillating World.
AB  - The notion that small changes can have large consequences in the climate or
      ecosystems has become popular as the concept of tipping points. Typically,
      tipping points are thought to arise from a loss of stability of an equilibrium
      when external conditions are slowly varied. However, this appealingly simple view
      puts us on the wrong foot for understanding a range of abrupt transitions in the
      climate or ecosystems because complex environmental systems are never in
      equilibrium. In particular, they are forced by diurnal variations, the seasons,
      Milankovitch cycles and internal climate oscillations. Here we show how abrupt
      and sometimes even irreversible change may be evoked by even small shifts in the
      amplitude or time scale of such environmental oscillations. By using model
      simulations and reconciling evidence from previous studies we illustrate how
      these phenomena can be relevant for ecosystems and elements of the climate system
      including terrestrial ecosystems, Arctic sea ice and monsoons. Although the
      systems we address are very different and span a broad range of time scales, the
      phenomena can be understood in a common framework that can help clarify and unify
      the interpretation of abrupt shifts in the Earth system.

PMID- 29568007
TI  - Author Correction: Improvement of Pharmacokinetic Profile of TRAIL via Trimer-Tag
      Enhances its Antitumor Activity in vivo.
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- 29568008
TI  - Voriconazole-induced photocarcinogenesis is promoted by aryl hydrocarbon receptor
      dependent COX-2 upregulation.
AB  - Voriconazole (VRCZ) induces the development of UV-associated skin cancers. The
      mechanism underlying the VRCZ-induced carcinogenesis has been largely unknown.
      Here, we showed that VRCZ metabolites plus UVA generated reactive oxygen species
      and resultant DNA damage of the epidermis, but did not induce substantial
      apoptosis in human keratinocytes (KCs). Furthermore, VRCZ per se stimulates aryl
      hydrocarbon receptor (AhR) and upregulates COX-2, which is a pivotal enzyme for
      the promotion of UV-associated tumors, in an AhR-ARNT dependent manner of the
      classical (genomic) pathway. Our findings suggest that the phototoxic moieties of
      VRCZ metabolites may participate in the initiation phase of VRCZ skin cancer,
      while VRCZ per se promotes the tumor development. Therefore, during VRCZ therapy,
      sun exposure protection is essential to prevent photocarcinogenesis caused by
      VRCZ metabolites plus UV. Chemoprevention with selective COX-2 inhibitors may be
      helpful to repress the development of skin cancers derived from DNA-damaged KCs.

PMID- 29568009
TI  - Low ocean-floor rises regulate subpolar sea surface temperature by forming
      baroclinic jets.
AB  - Sea surface temperature (SST) fronts in mid- to high-latitude oceans have
      significant impacts on extratropical atmospheric circulations and climate. In the
      western subarctic Pacific, sharp SST fronts form between the cold subarctic water
      and the recently found quasi-stationary jets that advect warm waters originating
      in the Kuroshio northeastward. Here we present a new mechanism of the jet
      formation paying attention to the propagation of baroclinic Rossby waves that is
      deflected by eddy-driven barotropic flows over bottom rises, although their
      height is low (~500 m) compared with the depth of the North Pacific Ocean (~6000
      m). Steered by the barotropic flows, Rossby waves bring a thicker upper layer
      from the subtropical gyre and a thinner upper layer from the subarctic gyre,
      thereby creating a thickness jump, hence a surface jet, where they converge. This
      study reveals an overlooked role of low-rise bottom topography in regulating SST
      anomalies in subpolar oceans.

PMID- 29568010
TI  - A Poroelastic Model of a Fibrous-Porous Tissue Engineering Scaffold.
AB  - Tissue engineering scaffolds are used in conjunction with stem cells for the
      treatment of various diseases. A number of factors provided by the scaffolds
      affect the differentiation of stem cells. Mechanical cues that are part of the
      natural cellular microenvironment can both accelerate the differentiation toward
      particular cell lineages or induce differentiation to an alternative cell fate.
      Among such factors, there are externally applied strains and mechanical
      (stiffness and relaxation time) properties of the extracellular matrix. Here, the
      mechanics of a fibrous-porous scaffold is studied by applying a coordinated
      modeling and experimental approach. A force relaxation experiment is used, and a
      poroelastic model associates the relaxation process with the fluid diffusion
      through the fibrous matrix. The model parameters, including the stiffness moduli
      in the directions along and across the fibers as well as fluid diffusion time,
      are estimated by fitting the experimental data. The time course of the applied
      force is then predicted for different rates of loading and scaffold porosities.
      The proposed approach can help in a reduction of the technological and
      experimental efforts to produce 3-D scaffolds for regenerative medicine as well
      as in a higher accuracy of the estimation of the local factors sensed by stem
      cells.

PMID- 29568011
TI  - Inhibitory effect of surface pre-reacted glass-ionomer (S-PRG) eluate against
      adhesion and colonization by Streptococcus mutans.
AB  - Surface Pre-reacted Glass-ionomer (S-PRG) filler is a bioactive filler produced
      by PRG technology, which has been applied to various dental materials. A S-PRG
      filler can release multiple ions from a glass-ionomer phase formed in the filler.
      In the present study, detailed inhibitory effects induced by S-PRG eluate
      (prepared with S-PRG filler) against Streptococcus mutans, a major pathogen of
      dental caries, were investigated. S-PRG eluate effectively inhibited S. mutans
      growth especially in the bacterium before the logarithmic growth phase.
      Microarray analysis was performed to identify changes in S. mutans gene
      expression in the presence of the S-PRG eluate. The S-PRG eluate prominently
      downregulated operons related to S. mutans sugar metabolism, such as the pdh
      operon encoding the pyruvate dehydrogenase complex and the glg operon encoding a
      putative glycogen synthase. The S-PRG eluate inhibited several in vitro
      properties of S. mutans relative to the development of dental caries especially
      prior to active growth. These results suggest that the S-PRG eluate may
      effectively inhibit the bacterial growth of S. mutans following downregulation of
      operons involved in sugar metabolism resulting in attenuation of the
      cariogenicity of S. mutans, especially before the active growth phase.

PMID- 29568012
TI  - Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and
      reinnervation.
AB  - Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and
      skeletal muscle. In muscle, it regulates neuromuscular junction gene expression,
      acetylcholine receptor number, muscle homeostasis and satellite cell survival.
      NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and
      their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve
      tissue after injury, but little is known about this system in skeletal muscle
      after denervation/reinnervation processes. Here, we performed a detailed time
      course expression analysis of several NRG1 isoforms and ErbB receptors in the rat
      superficial digitorum flexor muscle after three types of median nerve injuries of
      different severities. We found that ErbB receptor expression was correlated with
      the innervated state of the muscle, with upregulation of ErbB2 clearly associated
      with the denervation state. Interestingly, the NRG1 isoforms were differently
      regulated depending on the nerve injury type, leading to the hypothesis that both
      the NRG1alpha and NRG1beta isoforms play a key role in the muscle reaction to
      injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that
      both NRG1alpha and NRG1beta treatment influences the best-known atrophic
      pathways, suggesting that NRG1 might play an anti-atrophic role.

PMID- 29568014
TI  - Insufficient evidence for the role of school dental screening in improving oral
      health.
AB  - Data sourcesThe Cochrane Oral Health's Trials Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL), Medline, Embase, the US National
      Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health
      Organization International Clinical Trials Registry Platform databases.Study
      selectionRandomised controlled trials (cluster or parallel) evaluating school
      dental screening compared with no intervention or with one type of screening
      compared with another were included.Data extraction and synthesisTwo reviewers
      independently abstracted data and assessed risk of bias. Risk ratios were
      calculated for dichotomous outcomes, with data being pooled where appropriate.
      The GRADE approach was used to interpret findings.ResultsSix trials involving
      19,498 children were included. Two were considered to be at low risk of bias,
      three at unclear risk and one at high risk. No conclusions could be made from
      four studies comparing traditional screening versus no screening because the
      evidence was inconsistent. Two trials evaluating criteria-based screening versus
      no screening suggested a possible benefit; RR = 1.07 (95% CI; 0.99-1.16). No
      difference was found when comparing criteria-based screening with traditional
      screening, RR = 1.01, (95% CI; 0.94-1.08). No trials reported on long-term follow
      up or cost-effectiveness and adverse events.ConclusionsThe trials included in
      this review evaluated short-term effects of screening, assessing follow-up
      periods of three to eight months. We found very low certainty evidence that was
      insufficient to allow us to draw conclusions about whether there is a role for
      traditional school dental screening in improving dental attendance. For criteria
      based screening, we found low-certainty evidence that it may improve dental
      attendance when compared to no screening. However, when compared to traditional
      screening there was no evidence of a difference in dental attendance (very low
      certainty evidence).We found low-certainty evidence to conclude that personalised
      or specific referral letters improve dental attendance when compared to non
      specific counterparts. We also found low-certainty evidence that screening
      supplemented with motivation (oral health education and offer of free treatment)
      improves dental attendance in comparison to screening alone.We did not find any
      trials addressing cost-effectiveness and adverse effects of school dental
      screening.

PMID- 29568013
TI  - Dual binding in cohesin-dockerin complexes: the energy landscape and the role of
      short, terminal segments of the dockerin module.
AB  - The assembly of the polysaccharide degradating cellulosome machinery is mediated
      by tight binding between cohesin and dockerin domains. We have used an empirical
      model known as FoldX as well as molecular mechanics methods to determine the free
      energy of binding between a cohesin and a dockerin from Clostridium thermocellum
      in two possible modes that differ by an approximately 180 degrees  rotation. Our
      studies suggest that the full-length wild-type complex exhibits dual binding at
      room temperature, i.e., the two modes of binding have comparable probabilities at
      equilibrium. The ability to bind in the two modes persists at elevated
      temperatures. However, single-point mutations or truncations of terminal segments
      in the dockerin result in shifting the equilibrium towards one of the binding
      modes. Our molecular dynamics simulations of mechanical stretching of the full
      length wild-type cohesin-dockerin complex indicate that each mode of binding
      leads to two kinds of stretching pathways, which may be mistakenly taken as
      evidence of dual binding.

PMID- 29568015
TI  - Single dose oral prednisolone and post-operative endodontic pain.
AB  - DesignA randomised, single centre, double blind placebo controlled clinical trial
      involving 400 patients.InterventionThe inclusion criteria comprised systemically
      healthy patients between the ages of 18 and 35 years having mandibular molars
      with symptomatic irreversible pulpitis, radiographically normal periapical area
      and no pain on biting or percussion. The study was approved by the Institutional
      Review Board of Ethics Committee at the School of Dentistry, Cairo University,
      Egypt. Patients were recruited from the outpatient clinic of the Department of
      Endodontics.The independent Centre for Evidence Based Dentistry performed
      sequence generation and allocation concealment. For allocation concealment, two
      tablets of each medication were placed in sequentially numbered, opaque, sealed
      containers. Participants and operators were unaware of the assigned group for the
      duration of the study. Post-graduate students were calibrated to act as operators
      and supervisors from the department of endodontics evaluated their clinical
      performance.The participants received 40 mg of prednisolone or placebo tablets 30
      minutes before single visit root canal treatment. Patients recorded the pain
      level 6, 12 and 24 hours after treatment on a 100mm visual analogue scale. All
      patients received a sham capsule to take if needed as a postoperative analgesic.
      If pain persisted an analgesic was prescribed.Outcome measureThe primary outcome
      was the incidence of postoperative pain at three points; 6, 12 and 24 hrs. The
      secondary outcomes were pain intensity and the incidence of analgesic
      consumption. The relative risk reduction (RRR) and the number needed-to-treat
      (NNT) and their 95% confidence intervals (CI) were used to represent the risk of
      pain incidence.ResultsOf the 670 patients assessed for eligibility, 400 were
      included in the study. Only two patients of the 400 were lost to follow-up with
      398 patients (prednisolone group = 198; control group = 200) being included in
      the analysis; 259 were women and 141 men. The mean age was 29.45 -/+ 3.7 years in
      the prednisolone group and 28.97 -/+3.61 years in the control group. There was no
      significant difference for mean age (P = 0.164), gender distribution P = 0.123)
      or tooth type (P = 0.56) between the two groups. The relative risk reduction in
      pain incidence was 20.31% (95% CI: 12.03%, 27.82%) at six hours, 23.39% (95% CI:
      14.75%, 31.16%) at 12 hours and 28.85% (95% CI: 18.08%, 38.20%) at 24 hours.
      Prednisolone had significantly less post-obturation pain intensity compared to
      placebo at 6, 12 and 24 hours (P < 0.001). The relative risk reduction in sham
      capsule intake was 54% (95% CI: 38%, 66%) and in analgesic intake was 55% (95%
      CI: 3%, 79%). No adverse effects were recorded. The NNT (number needed to treat)
      was five (95% CI: 4, 9) at six hours, five (95% CI: 4, 8) at 12 hours and four at
      24 hours (95% CI: 3, 7).ConclusionsPreoperative oral administration of a single
      dose of 40 mg prednisolone was beneficial for the control of postoperative pain
      up to 24hrs after single visit root canal treatment in patients with symptomatic
      irreversible pulpitis. The incidence of postoperative pain level and the need for
      postoperative analgesic intake decreased. The non-invasive route and minimal
      possible adverse events results in a favourable risk benefit-balance.

PMID- 29568016
TI  - Too many reviews too few trials.

PMID- 29568017
TI  - The use of chlorhexidine in the prevention of alveolar osteitis after third molar
      extractions.
AB  - Data sourcesCochrane Central Register of Controlled Trials (CENTRAL), Medline
      through PubMed, Scopus, Science Direct, ISI Web of Science, Evidence-Based
      Dentistry, ClinicalTrials.gov, the European Union Clinical Trials Register, the
      Spanish General University Board database of doctoral theses in Spain (TESEO),
      the Spanish National Research Council (CSIC) bibliographic databases, and the
      Spanish Medical Index (IME).Study selectionRandomised controlled trials (RCTs)
      (with or without placebo) of patients of any age or gender who underwent
      maxillary or mandibular third molar extractions. Studies were required to have
      analysed the efficacy of only chlorhexidine in any concentration, formulation or
      treatment regimen for preventing alveolar osteitis (AO). There was no language
      restriction.Data extraction and synthesisData extraction was carried out
      independently by two researchers, and a third researcher was consulted in case of
      disagreements. When explicit data were not stated in the text, they were
      calculated using data from the tables where possible. In addition, authors were
      contacted to obtain any necessary missing information. Datasets were assessed for
      heterogeneity, and meta-analysis was conducted on homogenous datasets.
      Publication bias was assessed through funnel plots. The research was conducted
      and is reported in line with the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) statement.ResultsTwenty-three studies published from
      1979 to 2015, corresponding to 18 trials (16 parallel-group and two split-mouth
      RCTs), that reported on 2,824 third molar extractions (1,458 in experimental
      group and 1,366 in control group) were included. The overall relative risk (RR)
      was 0.53 (95% CI, 0.45-0.62; P<.0001). There was evidence of low heterogeneity
      (I2 = 9.3%; P = 0.336 by X2 test). The number needed to treat was eight (95% CI,
      7-11). There were no differences between chlorhexidine rinse (RR = 0.58; 95% CI,
      0.47-0.71) and gel (RR = 0.47; 95% CI, 0.37-0.60) for the prevention of AO after
      third molar extractions. Chlorhexidine did not cause more adverse reactions than
      placebo.ConclusionsThe use of chlorhexidine, in any formulation (rinse or gel),
      concentration (0.12% or 0.20%), or regimen (before, during and/or after surgery),
      is efficacious and effective in preventing AO in patients who have undergone
      third molar extraction. The findings showed that in order to prevent one case of
      AO, eight patients would have to be treated with chlorhexidine. Chlorhexidine gel
      was found to be moderately more efficacious than the rinse formulation.

PMID- 29568018
TI  - Cone-beam computed tomography or conventional radiography for localising of
      maxillary impacted canines?
AB  - Data sourcesPubMed, Web of Science, CINHAL and the Cochrane Library were searched
      until May 2016. Unpublished data were searched in Pro-Quest Dissertation,
      Abstracts and Thesis and Google Scholar, supplemented with manual search of the
      included studies references. No language restriction was used.Study selectionAll
      types of study designs were included, except case reports, comparing CBCT data
      with conventional radiographs. The primary outcome was: diagnostic accuracy
      between modalities, agreement in position, treatment planning and outcome
      efficacy. The secondary outcome was intermodality agreement in lateral root
      resorption detection and intra and inter-observer agreement values.Data
      extraction and synthesisTwo reviewers independently selected the studies for
      inclusion, performed data extraction and evaluated risk of bias. Discrepancies
      were resolved by discussions and reaching consensus. The Newcastle-Ottawa Scale
      was used to assess the risk of bias for case-controlled and cohort studies and a
      modified version for cross-sectional studies. The Quality Assessment of
      Diagnostic Accuracy (QUADAS-2) tool was used to rate diagnostic accuracy
      studies.ResultsEight studies met the inclusion criteria, two on diagnostic
      accuracy. The remaining six included 292 impacted canines in 224 patients.
      Outcomes were presented as calculated level of agreement and statistical
      significance for each primary outcome reported. Based on the diagnostic accuracy
      of two in vitro studies, the CBCT accuracy ranged from 50% to 95% while for
      conventional radiographs it ranged from 39% to 85%.The other six studies reported
      inter-modalities agreement in localisation (six studies) and treatment planning
      agreement (three studies). The inter-modalities agreement varied from 0.20 to
      0.82, with observed agreement of 64% to 84% in localisation of canine. The
      treatment planning agreement varied from 0.36 to 0.72.ConclusionsThe authors
      concluded that CBCT is more accurate than conventional radiographs in localising
      maxillary impacted canines and there is a broad range of inter-observer and
      modalities agreement for location and treatment planning. There is no robust
      evidence to support using CBCT as first line imaging method.

PMID- 29568019
TI  - Beneficial effects of supervised toothbrushing on caries incidence in children
      and adolescents are questioned.
AB  - Data sourcesThe Cochrane Central Register of Controlled Trials, Medline via
      PubMed, Web of Science, Embase, LILACS and BBO. Sources of grey literature
      included Open Grey, EThOS and Banco de Teses CAPES. Two international registers
      of ongoing trials were also searched (Current Controlled Trials and
      ClinicalTrials.gov). There were no language or date restrictions.Study
      selectionNo information is given in the manuscript or the published protocol on
      how the study selection was carried out, although the authors state that they
      followed PRISMA guidelines.Data extraction and synthesisData extraction and risk
      of bias assessment were carried out independently by two reviewers.ResultsFour
      studies were included; in all trials, supervised toothbrushing took place in
      schools. However, they differed in participant ages and caries risk as well as
      toothpaste fluoride concentration. Outcomes and outcome measures also varied. Two
      trials reported statistically significant differences in favour of supervised
      toothbrushing but lacked data on effect size and precision. No meta-analyses were
      carried out because of the high degree of heterogeneity between the
      studies.ConclusionsThe lack of high quality evidence meant that this systematic
      review was unable to reach a definitive conclusion on the effectiveness of
      supervised toothbrushing programmes on caries incidence in children and
      adolescents.

PMID- 29568020
TI  - Periodontal treatment for the prevention of adverse birth outcomes.
AB  - Data sourcesCochrane Oral Health and Pregnancy and Childbirth's Trial Registries,
      Cochrane Register of Controlled Trials, Cochrane Library, Medline Ovid, Embase
      Ovid and LILACS BIREME, clinicaltrials.com and the WHO Clinical Trials Registry
      Platform were searched for published and ongoing trials until October of
      2016.Study selectionRandomised controlled trials (RCTs) investigating the effects
      of periodontal treatment in reducing or preventing perinatal and maternal
      morbidity and mortality with no exclusions of language or date of publication.
      Primary perinatal outcomes included: gestational age at birth, birth weight,
      small for gestational age and perinatal mortality, while the primary maternal
      outcomes included mortality, pre-eclampsia and treatment adverse effects.Data
      extraction and synthesisTwo authors independently screened for inclusion and
      extracted data. Risk of bias was assessed using the Cochrane 'risk of bias'
      tool.Dichotomous results were expressed as risk ratios (RR) with a 95% confidence
      interval (CI), and continuous data were expressed as mean differences (MD) with
      95% confidence interval. Random-effects model was used for combining results.The
      quality of the evidence was assessed using GRADE.ResultsFifteen studies with a
      total of 7,161 participants met the inclusion criteria.Eleven studies (n = 5671)
      compared periodontal treatment with no treatment. For the outcome preterm birth
      before <37 weeks a calculated RR of 0.87, 95% CI 0.70-1.10 shows no clear
      difference. From seven studies (n = 3470) there is evidence that periodontal
      treatment may reduce birth weight <2500g (RR 0.77, 95% CI 0.48-0.95).There is
      unclear evidence on the effect of periodontal treatment on preterm birth <35
      weeks, <32 weeks, perinatal mortality and pre-eclampsia.Three studies with 3,610
      participants showed no evidence of difference in the outcome small for
      gestational age: RR 0.97, 95% CI 0.81-1.16.ConclusionsThere is no clear evidence
      that periodontal treatment during pregnancy has an effect on preterm birth. There
      is some evidence that it may reduce incidence of low birth weight.There is
      insufficient evidence to define what type of periodontal treatment is superior in
      preventing any adverse pregnancy outcome.

PMID- 29568021
TI  - Insufficient evidence to support or reject effect of conservative TMD therapies
      on otologic signs and symptoms.
AB  - Data sourcesThe search strategy focused on publications up to May 2015 in five
      electronic databases: PubMed, LILACS, Scopus, Web of Science and Science Direct.
      Furthermore, a partial grey literature search through Google Scholar and a hand
      search of the references of the included studies were also performed.Study
      selectionThose studies including patients with TMD associated with otologic signs
      and symptoms treated with conservative therapies, such as physiotherapy or
      cognitive behavioural therapy. These studies needed to describe whether the
      conservative treatments affected the associated otologic signs and symptoms. No
      language or time restrictions were applied.Data extraction and synthesisThe
      search was completed in two stages. 1st stage: titles and abstracts were screened
      and included (or excluded) independently by two reviewers. 2nd stage: the same
      selection criteria were applied to the full text of the previously selected
      studies by the same reviewers. Disagreements were discussed, and a third author
      was involved, when required, to make a final decision. Study quality was assessed
      by the two reviewers using two risk of bias tools: 'Quality Assessment of a
      Cohort Study' and 'Quality Assessment of a Randomised Clinical Trial'. Because of
      heterogeneity in the study designs only a narrative summary was
      presented.ResultsEight studies were finally included in this review. Three of
      them were randomised clinical trials and five were cohort studies. All studies
      had an acceptable risk of bias, except one with high risk of bias. Seven of the
      eight studies showed total or partial resolution of otologic signs and/or
      symptoms after TMD therapy.ConclusionsInsufficient evidence was identified to
      strongly support positive or negative changes in otologic signs and symptoms
      after conservative management therapies for TMD. Further studies with a higher
      level of evidence and more representative samples should be conducted to improve
      our understanding of the effect of TMD therapy on otologic complains.

PMID- 29568023
TI  - Which surgical approach for palatally displaced canines?
AB  - Data sourcesCochrane Oral Health's Trials Register, Cochrane Central Register of
      Controlled Trials, Medline Ovid and Embase Ovid (up to February 2017); ongoing
      clinical trials were searched in clinicaltrials.gov as well as the World Health
      Organization International Clinical Trials Registry. Reference lists of included
      studies and relevant systematic reviews were searched. No restrictions were
      placed on the language or date of publication and study authors were contacted
      when necessary.Study selectionRandomised and quasi-randomised controlled trials
      assessing open and closed surgical exposures in palatally displaced canines with
      no restriction on age, presenting malocclusion or type of orthodontic treatment.
      Unilaterally and bilaterally displaced canines were included in the review. The
      primary outcomes considered were sufficient eruption of the canine to allow
      orthodontic alignment without requiring additional surgery, post surgical
      complications and aesthetics.Data extraction and synthesisTwo authors
      independently screened titles and abstracts of all studies identified through the
      search and reviewed full articles against established inclusion criteria. Any
      disagreements between the authors were resolved by consensus or by consulting an
      expert. Risk of bias assessment was done using Cochrane Collaboration's tool and
      study authors were contacted for missing information. Dichotomous outcomes
      (success of surgery - yes or no) were expressed as risk ratio and 95% CI.
      Continuous outcomes (pain on VAS scale) were expressed as mean differences (MD)
      or standardised mean differences (if different scales were used).ResultsA total
      of three studies (six articles) representing 146 participants were included in
      the SR. One was an RCT while the other two were quasi-RCTs. With regards to
      successful eruption, there was no evidence of a difference between the open and
      closed groups (RR 0.99, 95% CI 0.93-1.06, P = 0.79). Other primary measures
      (including surgical complications or aesthetics) or secondary measures were
      either reported in just one trial or used different measures, so pooling of data
      was not possible.ConclusionsLimited available evidence suggests surgical exposure
      of palatally displaced canines is successful in bringing canines into alignment.
      However, data do not support one technique over the other (closed vs open). One
      trial was at low risk of bias while the others were at high risk of bias. This
      adds to the uncertainty of the conclusions.

PMID- 29568024
TI  - Is there an association between maternal smoking and oral clefts?
AB  - Data sourcesCochrane, PubMed and Ovid Medline. A search timeline of January 1966
      to May 2015 was used and language was restricted to English.Study selectionCase
      control and cohort studies relating to oral clefts, with information on maternal
      active smoking, before and after conception, excluding paternal smoking and
      exposure to environmental tobacco smoke.Data extraction and synthesisTwo authors
      extracted data independently. Both Begg's and Egger's funnel plots were used to
      assess publication bias. Sensitivity analysis was performed to assess impact of
      the different study types and chi-squared and P values were determined by SPSS
      software. Studies with missing data were excluded from the meta-analysis.ResultsA
      statistically significant association was found between maternal active smoking
      and CL +/- P (odds ratio [OR] 1.368; 95% confidence interval [CI] 1.259-1.486) as
      well as CP (OR 1.241; 95% CI 1.117-1.378). Half the studies showed positive dose
      response effect for each subgroup (test for linear trend, P <
      .05).ConclusionsWomen who smoke during pregnancy have a moderate risk of having a
      child with a CL +/- P or CP. A dose-response effect between maternal smoking and
      clefts was not established.

PMID- 29568025
TI  - Are pharmacological treatments for oro-facial pain effective?
AB  - Data sourcesElectronic searches of PubMed, the Cochrane Library, Embase, the
      National Health Service Economic Evaluation Database and HTA until March 2017.
      Also handsearched referenced in the original articles. Grey literature was not
      included.Study selectionRandomised controlled trials with more than ten
      participants with oro-facial pain duration of more than three months were sub
      grouped into: TMD-muscle pain (TMD-m), TMD-joint pain (TMD-j), burning mouth
      syndrome (BMS) and other oro-facial pain. Studies include any pharmacological
      treatment against another pharmacological, non-pharmacological treatment, placebo
      or no treatment. The primary outcome was change in pain intensity and the
      secondary outcome was the effect on quality of life.Data extraction and
      synthesisThree authors formed three review pairs that independently checked for
      inclusion. Four pairs of reviewers independently evaluated the risk of bias using
      the Swedish Agency for Health Technology Assessment and Assessment of Social
      Services tool. Two authors independently extracted data that were later assessed
      according to a modified GRADE system.ResultsForty-one studies, rated medium to
      low risk of bias, were included in qualitative analysis on patients with TMD-j
      pain (15 studies, n = 790), TMD-m pain (nine studies, n = 375), BMS (17 studies n
      = 868). For the TMD-j group five studies support NSAIDs and nine corticosteroid
      and hyaluronate injections. Eight of the nine TMD-m studies were included in a
      network meta-analysis (NMA), they support cyclobenzaprine, botulinum toxin
      injections and topical treatment with Ping-On ointment. Five of the 17 BMS
      studies included in a NMA support topical capsaicin and clonazepam. Of the
      remaining 12, five showed no effect while the remaining support alpha lipoic
      acid, gabapentin, clonazepam, amisulpride and SSRIs.ConclusionsBased on the
      results of the NMA the authors concluded that clonazepam and capsaicin are
      effective for BMS while cyclobenzaprine, a muscle relaxant, has a positive
      treatment effect on TMJ-m. Evidence from the narrative synthesis suggests NSAIDs,
      corticosteroid and hyaluronate injections are effective for TMD-j pain.

PMID- 29568026
TI  - Insufficient evidence for interventions to prevent dry mouth and salivary gland
      dysfunction post head and neck radiotherapy.
AB  - Data sourcesCochrane Oral Health's Trials Register, the Cochrane Central Register
      of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, EBSCO (Cumulative Index
      to Nursing and Allied Health Literature, LILACS, BIREME, Virtual Health Library
      (Latin American and Caribbean Health Science Information database), Zetoc
      Conference Proceedings, the US National Institutes of Health Ongoing Trials
      Register, (ClinicalTrials.gov) and the World Health Organization International
      Clinical Trials Registry Platform for ongoing trials. No restrictions were placed
      on the language or date of publication when searching the electronic
      databases.Study selectionThe review included randomised controlled trials,
      irrespective of their language of publication or publication status. Participants
      could be outpatients or inpatients. The review included trials comparing any
      pharmacological agent regimen, prescribed prophylactically for salivary gland
      dysfunction prior to or during radiotherapy, with placebo, no intervention or an
      alternative pharmacological intervention. Comparisons of radiation techniques
      were excluded.Data extraction and synthesisStandard Cochrane methodological
      processes were followed.ResultsThirty-nine studies that randomised 3520
      participants were included; the number of participants analysed varied by outcome
      and time point. The studies were ordered into 14 separate comparisons with meta
      analysis only being possible in three of those. We found low quality evidence to
      show that amifostine, when compared to a placebo or no treatment control, might
      reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4
      scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval
      (CI) 0.19 to 0.67; P = 0.001, three studies, 119 participants), and up to three
      months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, five studies,
      687 participants), but there is insufficient evidence that the effect is
      sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P =
      0.21, seven studies, 682 participants). We found very low quality evidence that
      amifostine increased unstimulated salivary flow rate up to 12 months after
      radiotherapy, both in terms of mg of saliva per five minutes (mean difference
      (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, one study, 27 participants), and
      incidence of producing greater than 0.1 g of saliva over five minutes (RR 1.45,
      95%CI 1.13 to 1.86; P = 0.004, one study, 175 participants).However, there was
      insufficient evidence to show a difference when looking at stimulated salivary
      flow rates. There was insufficient (very low quality) evidence to show that
      amifostine compromised the effects of cancer treatment when looking at survival
      measures. There was some very low quality evidence of a small benefit for
      amifostine in terms of quality of life (ten-point scale) at 12 months after
      radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, one study, 180
      participants), but insufficient evidence at the end of and up to three-month post
      radiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and
      24-month post radiotherapy.There was low quality evidence that amifostine is
      associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P <
      0.00001, five studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to
      29.83; P = 0.0002, three studies, 376 participants); nausea (RR 2.60, 95% CI 1.81
      to 3.74; P < 0.00001, four studies, 556 participants); and allergic response (RR
      7.51, 95% CI 1.40 to 40.39; P = 0.02, three studies, 524 participants).The
      authors founded insufficient evidence (that was of very low quality) to determine
      whether or not pilocarpine performed better or worse than a placebo or no
      treatment control for the outcomes: xerostomia, salivary flow rate, survival and
      quality of life. There was some low quality evidence that pilocarpine was
      associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004,
      five studies, 389 participants).The authors found insufficient evidence to
      determine whether or not palifermin performed better or worse than placebo for:
      xerostomia (low quality); survival (moderate quality); and any adverse effects.
      There was also insufficient evidence to determine the effects of the following
      interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol,
      artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge,
      polaprezinc, azulene rinse and Venalot Depot (coumarin plus
      troxerutin).ConclusionsThere is some low quality evidence to suggest that
      amifostine prevents the feeling of dry mouth in people receiving radiotherapy to
      the head and neck (with or without chemotherapy) in the short- (end of
      radiotherapy) to medium-term (three-month post radiotherapy). However, it is less
      clear whether or not this effect is sustained to 12-month post radiotherapy. The
      benefits of amifostine should be weighed against its high cost and side effects.
      There was insufficient evidence to show that any other intervention is
      beneficial.

PMID- 29568027
TI  - Chlorhexidine gel to prevent alveolar osteitis following mandibular third molar
      extractions.
AB  - Data sourcesMedline/PubMed, Cochrane central, Scopus and Google scholar.Study
      selectionRandomised controlled trials (RCTs) published in English between January
      2010 and December 2015 were identified by two reviewers. Unpublished studies were
      not considered.Data extraction and synthesisStandard Cochrane Collaboration
      assessment tools were used to carry out a risk of bias assessment. The following
      data were collected from the articles; sample size, country, mean age of
      participants, diagnosis of alveolar osteitis (AO), type of intervention and
      outcomes. Heterogeneity (I2) was calculated to determine the statistical model to
      be used for meta-analysis.ResultsTen randomised control trials (RCTs) were
      included, with 862 participants. Eight studies used 0.2% chlorhexidine (CHX) gel
      in the experimental group, 1% CHX gel in one study, and in one study the
      concentration was not specified. Two studies used adjunctive antibiotics, and one
      study gave 400mg Ibuprofen to all participants.Six of the RCTs were at low risk
      of bias, three studies showed possible selection and/or performance bias, and one
      study gave no information on bias. Heterogeneity was low level (I2 = 40%) and a
      funnel plot presented a low level of publication bias.The included RCTs used
      Blum's criteria for diagnosis of AO. Six of the RCTs were conducted double
      blinded. The risk ratio (RR) was calculated for each RCT and also for the pooled
      effect. The overall pooled effect of CHX gel placed in the extraction socket
      following mandibular 3rd molar removal was calculated to have prevented 57% of AO
      instances (RR = 0.43, 95% CI: 0.32, 0.58; p<0.00001). Subgroup analysis of the
      effect of CHX gel in participants who smoked/used the oral contraceptive pill
      (OCP) was calculated to have prevented 40% of AO (RR = 0.60, 95% CI: 0.41, 0.87;
      p = 0.007). In the studies that used a split-mouth design, CHX gel prevented 71%
      of AO incidence (RR = 0.29, 95% CI: 0.16, 0.50; p <0.0001).ConclusionsThis meta
      analysis and systematic review concluded 'clinically significant evidence that
      CHX gel application in the extraction socket of mandibular 3rd molar has reduced
      the incidence of alveolar osteitis'.

PMID- 29568028
TI  - Breastfeeding and occlusal development.
AB  - Data sourcesPubmed, Embase, Scopus databases and New York Academy of Medicine
      Grey Literature Report. There were no restrictions on language and publication
      dates.Study selectionTwo reviewers selected both prospective and retrospective
      studies of children who had either been exclusively breastfed or were mixed
      breastfed; who were in either the primary or mixed dentition, and malocclusion
      was assessed. The following malocclusion traits were included; Class 2 molar,
      open-bite, non-spaced dentition and posterior crossbite.Data extraction and
      synthesisData were extracted including type of dentition, type of malocclusion,
      breastfeeding data collection method, results, breast feeding malocclusion odds
      ratio (OR) and quality of the article. The ORs of associations between different
      lengths of breastfeeding and the various malocclusion traits were
      calculated.ResultsThirty-one studies were included in a qualitative synthesis,
      nine in the quantitative analysis. All studies were observational, a majority
      examining malocclusion in the mixed dentition. Two studies looked at associations
      between no breastfeeding and posterior crossbite, finding children not breastfed
      presented 1.7 times more posterior crossbite than those breastfed for between one
      and six months (OR = 1.70 CI 2.01-2.39). ORs were calculated for exclusive
      breastfeeding and posterior crossbite with different duration of breastfeeding,
      and duration of breastfeeding and posterior crossbite. With regard to open bite
      and breastfeeding the OR=1.76 (CI 0.55-5.61) comparing those who were breastfed
      for less than or more than six months. Children breastfed for up to six months
      presented 1.25 times more Class 2 molar relationships than those breastfed for
      over six months. Children breastfed for up to six months presented 1.73 times
      more non-spaced dentitions than those breastfed for over six months (OR =1.73, CI
      1.35-2.22).ConclusionsBreastfeeding is a protective factor against posterior
      crossbites and Class 2 malocclusion in primary and mixed dentitions, with the
      protective effect increasing with the months of breastfeeding. There is no clear
      evidence for breastfeeding proving any benefit against other malocclusion risks;
      open bite and non-spaced dentitions.

PMID- 29568029
TI  - Limited evidence on best material for retrograde root fillings.
AB  - Data sourcesCochrane Oral Health's Trials Register, the Cochrane Central Register
      of Controlled Trials (CENTRAL), Medline Ovid, Embase Ovid, LILACS, BIREME Virtual
      Health Library, OpenSIGLE, ClinicalTrials.gov, the World Health Organization
      International Clinical Trials Registry Platform, Chinese BioMedical Literature
      Database, VIP (in Chinese), China National Knowledge Infrastructure and
      Sciencepaper Online. No restrictions on language or date of publication were
      placed.Study selectionRandomised controlled trials (RCTs) that compared different
      retrograde filling materials, with clinical or radiological assessment for
      success over a minimum follow-up period of 12 months.Data extraction and
      synthesisTwo review authors extracted data independently and in duplicate, and
      subsequently carried out risk of bias assessment for each eligible study
      following Cochrane methodological guidelines. Original trial authors were
      contacted for any missing information.ResultsSix randomised controlled trials
      were included, with 916 participants involving 988 teeth. All these studies had a
      high risk of bias. Comparisons of five different retrograde filling materials
      were undertaken, including MTA versus intermediate restorative material (IRM),
      MTA versus super ethoxybenzoic acid cement (Super-EBA), Super-EBA versus IRM,
      dentine-bonded resin composite versus glass ionomer cement and glass ionomer
      cement versus amalgam.Grouping of data from different studies was minimal and
      provided limited evidence for each comparison. All studies showed a risk ratio of
      approximately one, indicating that there is weak or little evidence that any of
      the materials are superior. All of the studies displayed very low quality of
      evidence. None of these studies reported adverse events.ConclusionsCurrently
      there is insufficient evidence to determine which material is preferable for
      retrograde filling. Further high-quality RCTs are required for this.

PMID- 29568030
TI  - Periodontal disease has an impact on patients' quality of life.
AB  - Data sourcesMedline, Embase, OpenGrey, Journal of Clinical Periodontology,
      Journal of Periodontology and a hand search of the bibliographies of retrieved
      publications.Study selectionTwo reviewers screened the title and abstract of 1134
      studies from the literature and selected 37 suitable publications for inclusion
      following full text analysis of 109 papers and agreement between both reviewers.
      The search included observational, epidemiological studies and clinical trials
      that fufilled the inclusion criteria. The publications assessed contained a
      periodontal clinical examination and a validated OHRQoL questionnaire. There were
      no language restrictions and the review was performed according to the MOOSE
      statement.Data extraction and synthesisData were extracted from each study
      applying the PECO format. The quality of the observational studies was evaluated
      by the Newcastle Ottawa Scale (NOS) and clinical trials by the (MINORS)
      methodological index for non-randomised studies. The Strength of Grading Taxonomy
      (SORT) was utilised to assess the level of evidence and strength of
      recommendation of the included studies. A meta-analysis was not undertaken due
      the heterogeneity of the included studies, therefore results were synthesised by
      applying a vote counting method.ResultsThirty-seven studies included in the
      review were evaluated by the vote counting method. According to NOS and MINORS
      the risk of bias was identified as moderate with most studies assessing 50% to
      83% of the parameters established. A level two for quality of evidence and a
      level B for strength of recommendation were applicable for the relationship
      between clinically diagnosed periodontal disease and OHRQoL. The evidence level
      was consistent across the studies. Nineteen of the studies examined a distinct
      population group with respect to diagnosis of systemic disease, socioeconomic
      status, demographic background or periodontal diagnosis. Twenty-eight of the
      included studies reported an association between periodontal diseases and OHRQoL
      while eight of the publications highlighted a dose-response relationship between
      and extent and severity of periodontal disease and the impact on
      OHRQoL.ConclusionsThe findings support the association between clinically
      diagnosed periodontal diseases and subjectively assessed OHRQoL with a dose
      response relationship demonstrated. In summation, periodontal diseases play a
      significant role in oral health and impact on the QoL of affected individuals. In
      publications that undertook a full mouth recording the results were more evident,
      therefore a comprehensive periodontal exam in conjunction with a validated OHRQoL
      questionnaire is recommended.

PMID- 29568031
TI  - Author Correction: Lactate oxidation facilitates growth of Mycobacterium
      tuberculosis in human macrophages.
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- 29568032
TI  - Mesoproterozoic juvenile crust in microcontinents of the Central Asian Orogenic
      Belt: evidence from oxygen and hafnium isotopes in zircon.
AB  - We report in situ O and Hf isotope data of zircon grains from coeval
      Mesoproterozoic (ca. 1.4 Ga) igneous metamafic (amphibolite) and granitic rocks
      of the Chinese Central Tianshan microcontinent (CTM) in the southern Central
      Asian Orogenic Belt (CAOB). Zircon grains from amphibolite have mantle-like
      delta18OVSMOW values of 4.7-5.60/00 and juvenile Hf isotopic compositions
      (epsilonHf(t) = 8.4-15.3; TDMC = 1.57-1.22 Ga), whereas those from granitic rocks
      have delta18OVSMOW values of 5.6-7.00/00 and evolved Hf isotopic compositions
      (epsilonHf(t) = -1.0-8.2; TDMC = 2.09-1.62 Ga). Zircon O-Hf isotopic compositions
      of the metamafic and granitic rocks provide evidence for Mesoproterozoic (ca. 1.4
      Ga) crustal growth and a substantial Palaeoproterozoic supracrustal component in
      the CTM. These findings and previous studies, reporting ca. 1.4 Ga magmatic rocks
      from other microcontinents of the CAOB, suggest that a large belt of
      Mesoproterozoic (ca. 1.4 Ga) juvenile continental crust formed in a continental
      terrane, fragments of which now occur over a distance of more than a thousand
      kilometres in the southern CAOB.

PMID- 29568033
TI  - Adsorption-based atmospheric water harvesting device for arid climates.
AB  - Water scarcity is a particularly severe challenge in arid and desert climates.
      While a substantial amount of water is present in the form of vapour in the
      atmosphere, harvesting this water by state-of-the-art dewing technology can be
      extremely energy intensive and impractical, particularly when the relative
      humidity (RH) is low (i.e., below ~40% RH). In contrast, atmospheric water
      generators that utilise sorbents enable capture of vapour at low RH conditions
      and can be driven by the abundant source of solar-thermal energy with higher
      efficiency. Here, we demonstrate an air-cooled sorbent-based atmospheric water
      harvesting device using the metal-organic framework (MOF)-801
      [Zr6O4(OH)4(fumarate)6] operating in an exceptionally arid climate (10-40% RH)
      and sub-zero dew points (Tempe, Arizona, USA) with a  thermal efficiency (solar
      input to water conversion) of ~14%. We predict that this device delivered over
      0.25 L of water per kg of MOF for a single daily cycle.

PMID- 29568034
TI  - Author Correction: Deep sequencing reveals the first fabavirus infecting peach.
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- 29568035
TI  - Integrating Free-Form Nanostructured GRIN Microlenses with Single-Mode Fibers for
      Optofluidic Systems.
AB  - We present both a theoretical and an experimental study of a novel compact lensed
      fiber system utilizing a nanostructured GRIN lens. The lens can be integrated
      with an optical fiber, which ensures a unique and efficient focusing in any high
      index medium, such as a liquid. We use the effective medium approach to design
      lenses with arbitrary refractive index. To fabricate lenses, we utilize a
      discrete array of nano-sized rods made of two types of glasses, and apply a
      standard stack-and-draw fiber drawing technology. The fabricated nanostructured
      GRIN lenses have a parabolic refractive index profile with a diameter of a
      standard fiber, very short working distances (55 um in the air) and a high
      numerical aperture (NA = 0.16). As a proof-of-concept of the new micro-lensed
      fiber system, we demonstrate an experiment on optical trapping of micrometer
      sized glass beads. We also show that our method is compatible with optical fiber
      technology and allows for any shape of the refractive index distribution in 2D.
      Thanks to that a new functionality could be achieved by replacing the GRIN lens
      with an axicon lens, vortex type elements, micro-lenses arrays or diffraction
      elements.

PMID- 29568036
TI  - Vaccine mandates, public trust, and vaccine confidence: understanding perceptions
      is important.
AB  - The experience in Australia with penalizing parents who refuse to have their
      children vaccinated demonstrates the need to study and understand resistance to
      vaccination as a global phenomenon with particular local manifestations.

PMID- 29568037
TI  - Interfacial Hydrolysis of Acetals on Protonated TEMPO-oxidized Cellulose
      Nanofibers.
AB  - 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose nanofibers
      (TOCNs), which have a high-density of exposed carboxylic acid groups on their
      crystalline surfaces, effectively act as acid catalysts in acetal hydrolysis.
      Carboxy-free cellulose nanofibers, polymeric carboxylic acids, and homogeneous
      acetic acid do not show significant catalytic activity under the same reaction
      conditions. Mercerized TOCNs differing from the original TOCNs in a crystalline
      structure were also ineffective, which suggests that the unique nanoarchitectural
      features of TOCNs, such as regularly aligned carboxylic acid groups, large
      specific surface areas, and structural rigidity, must be major factors in the
      acceleration of acetal hydrolysis. Kinetic analysis suggested that substrates
      and/or acid catalyst species were concentrated on the TOCN crystalline surfaces,
      which significantly enhanced the catalytic activity.

PMID- 29568038
TI  - Frequency of Esophageal Eosinophilia in a Pediatric Population from Central
      Brazil.
AB  - Here we report a retrospective cross-sectional study on Esophageal eosinophilia
      (EsEo) frequency in Brazil, for 2, 425 pediatric patients with symptoms
      associated with gastroesophageal diseases in 2012. EsEo is defined by >=15
      eosinophils per high power field (400x) and confirmed through histological
      analyses of esophageal biopsies. Overall, 126 patients had EsEo equating to a
      frequency of 5.2%. There was a significant difference between the endoscopic
      features of patients with EsEo, where 10.7% had erosive esophagitis, 3.0% had non
      erosive esophagitis and 1% showed normal esophageal mucosa. According to the
      interaction of the variables in the Classification and Regression Tree Analysis,
      most patients diagnosed with EsEo were older males with erosive esophagitis. On
      the other hand, the lowest frequency of EsEo was found among younger females with
      non-erosive esophagitis/normal mucosa. Environmental conditions, including
      climate variation and changes, were observed in association with EsEo, supporting
      a potential role for environmental factors in its pathogenesis. There was an
      inverse correlation between the number of EsEo, rainfall and humidity. EsEo is a
      relatively frequent finding in the pediatric population of Brazil with symptoms
      of gastroesophageal diseases. Both clinical and histological examinations of
      patients are important for a reliable diagnostic of EsEo cases and to patient
      care.

PMID- 29568039
TI  - Author Correction: High-pressure versus low-pressure home non-invasive positive
      pressure ventilation with built-in software in patients with stable hypercapnic
      COPD: a pilot 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- 29568040
TI  - Drivers of solar radiation variability in the McMurdo Dry Valleys, Antarctica.
AB  - Annually averaged solar radiation in the McMurdo Dry Valleys, Antarctica has
      varied by over 20 W m-2 during the past three decades; however, the drivers of
      this variability are unknown. Because small differences in radiation are
      important to water availability and ecosystem functioning in polar deserts,
      determining the causes are important to predictions of future desert processes.
      We examine the potential drivers of solar variability and systematically
      eliminate all but stratospheric sulfur dioxide. We argue that increases in
      stratospheric sulfur dioxide increase stratospheric aerosol optical depth and
      decrease solar intensity. Because of the polar location of the McMurdo Dry
      Valleys (77-78 degrees S) and relatively long solar ray path through the
      stratosphere, terrestrial solar intensity is sensitive to small differences in
      stratospheric transmissivity. Important sources of sulfur dioxide include natural
      (wildfires and volcanic eruptions) and anthropogenic emission.

PMID- 29568041
TI  - Prior Expectation Modulates Repetition Suppression without Perceptual Awareness.
AB  - Stimulus repetition induces attenuated brain responses. This phenomenon, termed
      repetition suppression (RS), is classically held to stem from bottom-up neuronal
      adaptation. However, recent studies suggest that RS is driven by top-down
      predictive mechanisms. It remains controversial whether these top-down mechanisms
      of RS rely on conscious strategies, or if they represent a more fundamental
      aspect of perception, coding for physical properties of the repeated feature. The
      presence of top-down effects in the absence of perceptual awareness would
      indicate that conscious strategies are not sufficient to explain top-down
      mechanisms of RS. We combined an unconscious priming paradigm with EEG recordings
      and tested whether RS can be modulated by the probability of encountering a
      repetition, even in the absence of awareness. Our results show that both
      behavioural priming and RS near occipital areas are modulated by repetition
      probability, regardless of prime awareness. This contradicts previous findings
      that have argued that RS modulation is a by-product of conscious strategies. In
      contrast, we found that the increase in theta-band power following unrepeated
      trials - an index of conflict detection - is modulated only by expectations
      during conscious primes, implicating the use of conscious strategies. Together,
      our results suggest that the influence of predictions on RS can be either
      automatic in sensory brain regions or dependent on conscious strategies.

PMID- 29568042
TI  - Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of
      Gastric Myoelectric Activity in Ambulatory Subjects.
AB  - The increasing prevalence of functional and motility gastrointestinal (GI)
      disorders is at odds with bottlenecks in their diagnosis, treatment, and follow
      up. Lack of noninvasive approaches means that only specialized centers can
      perform objective assessment procedures. Abnormal GI muscular activity, which is
      coordinated by electrical slow-waves, may play a key role in symptoms. As such,
      the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric
      electrical activity, can be used to inform diagnoses over broader populations.
      However, it is seldom used due to technical issues: inconsistent results from
      single-channel measurements and signal artifacts that make interpretation
      difficult and limit prolonged monitoring. Here, we overcome these limitations
      with a wearable multi-channel system and artifact removal signal processing
      methods. Our approach yields an increase of 0.56 in the mean correlation
      coefficient between EGG and the clinical "gold standard", gastric manometry,
      across 11 subjects (p < 0.001). We also demonstrate this system's usage for
      ambulatory monitoring, which reveals myoelectric dynamics in response to meals
      akin to gastric emptying patterns and circadian-related oscillations. Our
      approach is noninvasive, easy to administer, and has promise to widen the scope
      of populations with GI disorders for which clinicians can screen patients,
      diagnose disorders, and refine treatments objectively.

PMID- 29568043
TI  - First detection of human hepegivirus-1 (HHpgV-1) in Iranian patients with
      hemophilia.
AB  - A novel blood-borne virus called the human hepegivirus 1 (HHpgV-1) was recently
      discovered in hemophilia patients. The present study aimed to investigate the
      presence of HHpgV-1 in hemophilia patients. A total of 436 serum samples were
      investigated for the presence of hepatitis C virus (HCV), human pegivirus-1 (HPgV
      1), torque teno virus (TTV), and HHpgV-1. Out of the 436 patients, 163 (37.4%),
      19 (4.4%), 76 (17.4%), and four (0.9%) patients were positive for HCV, HPgV-1,
      TTV, and HHpgV-1, respectively. HHpgV-1 patients had a mean viral load of 4.9 +/-
      0.3 log RNA copies/mL and were co-infected with HCV-1a, HPgV-1, and TTV.
      Moreover, three HHpgV-1-positive patients exhibited stage F0 liver fibrosis. HCV
      viral load in HHpgV-1-positive patients was lower than those of HHpgV-1-negative
      patients. Results also revealed that co-infection of HHpgV-1 with HPgV-1 and HCV
      may play a protective role in patients with chronic HCV. In conclusion, we
      detected a low frequency of HHpgV-1 infection in hemophilia patients, and results
      suggested that HHpgV-1 infection was correlated with the presence of other blood
      borne viruses and is likely to also correlate with low HCV viral load and reduced
      severity of liver disease. Additional studies are required to further investigate
      the clinical importance of HHpgV-1.

PMID- 29568044
TI  - Multi-Target Tracking of Human Spermatozoa in Phase-Contrast Microscopy Image
      Sequences using a Hybrid Dynamic Bayesian Network.
AB  - Male infertility is mostly related to semen and spermatozoa, and any diagnosis or
      treatment requires the investigation of the motility patterns of spermatozoa. The
      movements of spermatozoa are fast and involve collision and occlusion with each
      other. In order to extract the motility patterns of spermatozoa, multi-target
      tracking (MTT) of spermatozoa is necessary. One of the most important steps of
      MTT is data association, in which the newly arrived observations are used to
      update the previous tracks. Dynamic Bayesian network (DBN) is a powerful tool for
      modeling and solving various types of problems such as tracking and
      classification. There can also be a hybrid-DBN (HDBN), in which both continuous
      and discrete nodes are present. HDBN has a suitable structure for modeling
      problems that have both discrete and continuous parameters like MTT. In this
      research, the data association for MTT of human spermatozoa has been studied. The
      proposed algorithm was tested over hundreds of manually extracted spermatozoa
      tracks and evaluated using several standard measures. The superior results of the
      proposed algorithm in comparison to the other well-known algorithms, show that it
      could be considered as an improved alternative to traditional computer assisted
      sperm analysis (CASA) algorithms.

PMID- 29568045
TI  - Tracing intensive fish and meat consumption using Zn isotope ratios: evidence
      from a historical Breton population (Rennes, France).
AB  - Here we report Sr and Zn isotope ratios of teeth of medieval to early modern
      Breton people a population whose diet is known from historical, archeological and
      collagen isotope data. Most of the population, buried in the Dominican convent of
      Rennes, France, consists of parliamentary nobles, wealthy commoners and
      ecclesiastics, who had a diet rich in animal products. Our aim is to assess how
      the Zn isotope ratios of their teeth compare to those of other French historical
      populations previously studied, which were characterized by cereal-based diets,
      and those of modern French individuals, who daily eat animal products. We
      describe a clear offset (~0.350/00) between local and non-local human individuals
      in Zn isotope ratios. The delta66Zntooth values of local individuals overlap that
      of modern French people, and are lower than those of local carnivores. Non-local
      delta66Zn values are similar to those of historical individuals analyzed
      previously. We conclude the lower Zn isotope ratios of local humans relative to
      the associated fauna can be explained by the consumption of carnivorous fish and
      pork, in agreement with historical, zooarchaeological and collagen (C, N, S)
      isotope data. Zn isotopes could therefore be a tracer of fish and/or substantial
      meat consumption in ancient populations.

PMID- 29568046
TI  - Biological characterization of Aedes albopictus (Diptera: Culicidae) in
      Argentina: implications for arbovirus transmission.
AB  - Aedes albopictus (Diptera: Culicidae) is an invasive mosquito, native to Asia,
      that has expanded its range worldwide. It is considered to be a public health
      threat as it is a competent vector of viruses of medical importance, including
      dengue, chikungunya, and Zika. Despite its medical importance there is almost no
      information on biologically important traits of Ae. albopictus in Argentina. We
      studied life cycle traits, demographic parameters and analyzed the competence of
      this mosquito as a virus vector. In addition, we determined the prevalence of
      Wolbachia strains in Ae. albopictus as a first approach to investigate the
      potential role of this bacteria in modulating vector competence for arboviruses.
      We observed low hatch rates of eggs, which led to a negative growth rate. We
      found that Ae. albopictus individuals were infected with Wolbachia in the F1 but
      while standard superinfection with wAlbA and wAlbB types was found in 66.7% of
      the females, 16.7% of the females and 62.5% of the males were single-infected
      with the wAlbB strain. Finally, despite high levels of infection and
      dissemination, particularly for chikungunya virus, Ae. albopictus from
      subtropical Argentina were found to be relatively inefficient vectors for
      transmission of both chikungunya and dengue viruses.

PMID- 29568047
TI  - Transparent semiconducting SrTiO3 crystal fabricated by heating treatment with
      gaseous ammonia and CeO2 powder.
AB  - A transparent semiconducting SrTiO3 single crystal with a resistivity of the
      order of 103 Omega.cm was fabricated by heating a SrTiO3 single crystal with
      gaseous ammonia and CeO2 powder. Conductive atomic force microscope (C-AFM)
      measurement revealed that micro-sized voids were formed and the high conductivity
      was exhibited only at around the voids. It is considered that the micro-sized
      voids were caused by the concentrated SrO planar defects, and TiO2-terminated
      structure with oxygen vacancies contributed to the two-dimensional conduction. In
      the heating process, the CeO2 powder acted as an oxygen source, and radicals such
      as NH2 and NH were generated by the reaction of oxygen and ammonia. The radicals
      may have contributed to the formation of three-dimensional network of the
      conductive paths consisting of SrO planar defects without the reduction of the
      bulk components. The electrons were localized on the TiO2-terminated structure,
      and the volume content of the conductive paths was small compared to the
      insulating bulk component. Therefore, the crystal was optically transparent and
      semiconducting.

PMID- 29568048
TI  - Electrospinning over Solvent Casting: Tuning of Mechanical Properties of
      Membranes.
AB  - We put forth our opinion regarding the enhanced plasticity and modulation of
      mechanical properties of polymeric films obtained through electrospinning process
      in this article. In majority of the pharmaceutical, biomedical, and packaging
      applications, it is desirable that polymer based matrices should be soft,
      flexible, and have a moderate toughness. In order to convert inflexible and
      brittle polymers, adjuvants in the form of plasticizers are added to improve the
      flexibility and smoothness of solvent casted polymer films. However, many of
      these plasticizers are under scrutiny for their toxic effects and environmental
      hazards. In addition, plasticizers also increase the cost of end products. This
      has motivated the scientific community to investigate alternate approaches. The
      changes imparted in membrane casted by electrospinning were tried to be proved by
      SEM, Mechanical property study, DSC and XRD studies. We have showed dramatic
      improvement in flexibility of poly(epsilon-caprolactone) based nanofiber matrix
      prepared by electrospinning method whereas solvent casting method without any
      plasticizer produced very brittle, inflexible film of PCL. Modulation capacity of
      mechanical properties is also recorded. We tried to support our opinion by citing
      several similar findings available in the open literature. The electrospinning
      method helps in plasticization and in tuning mechanical properties.

PMID- 29568049
TI  - Made in translation.

PMID- 29568050
TI  - Foldamers wave to the ribosome.

PMID- 29568051
TI  - Organic synthesis provides opportunities to transform drug discovery.
AB  - Despite decades of ground-breaking research in academia, organic synthesis is
      still a rate-limiting factor in drug-discovery projects. Here we present some
      current challenges in synthetic organic chemistry from the perspective of the
      pharmaceutical industry and highlight problematic steps that, if overcome, would
      find extensive application in the discovery of transformational medicines.
      Significant synthesis challenges arise from the fact that drug molecules
      typically contain amines and N-heterocycles, as well as unprotected polar groups.
      There is also a need for new reactions that enable non-traditional
      disconnections, more C-H bond activation and late-stage functionalization, as
      well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C-X
      or C-C bond formation. We also emphasize that syntheses compatible with
      biomacromolecules will find increasing use, while new technologies such as
      machine-assisted approaches and artificial intelligence for synthesis planning
      have the potential to dramatically accelerate the drug-discovery process. We
      believe that increasing collaboration between academic and industrial chemists is
      crucial to address the challenges outlined here.

PMID- 29568052
TI  - Strategies for microbial synthesis of high-value phytochemicals.
AB  - Phytochemicals are of great pharmaceutical and agricultural importance, but often
      exhibit low abundance in nature. Recent demonstrations of industrial-scale
      production of phytochemicals in yeast have shown that microbial production of
      these high-value chemicals is a promising alternative to sourcing these molecules
      from native plant hosts. However, a number of challenges remain in the broader
      application of this approach, including the limited knowledge of plant secondary
      metabolism and the inefficient reconstitution of plant metabolic pathways in
      microbial hosts. In this Review, we discuss recent strategies to achieve
      microbial biosynthesis of complex phytochemicals, including strategies to: (1)
      reconstruct plant biosynthetic pathways that have not been fully elucidated by
      mining enzymes from native and non-native hosts or by enzyme engineering; (2)
      enhance plant enzyme activity, specifically cytochrome P450 activity, by
      improving efficiency, selectivity, expression or electron transfer; and (3)
      enhance overall reaction efficiency of multi-enzyme pathways by dynamic control,
      compartmentalization or optimization with the host's metabolism. We also
      highlight remaining challenges to - and future opportunities of - this approach.

PMID- 29568053
TI  - Hidden hassium.

PMID- 29568054
TI  - Atomic women.

PMID- 29568055
TI  - High-capacity optical long data memory based on enhanced Young's modulus in
      nanoplasmonic hybrid glass composites.
AB  - Emerging as an inevitable outcome of the big data era, long data are the massive
      amount of data that captures changes in the real world over a long period of
      time. In this context, recording and reading the data of a few terabytes in a
      single storage device repeatedly with a century-long unchanged baseline is in
      high demand. Here, we demonstrate the concept of optical long data memory with
      nanoplasmonic hybrid glass composites. Through the sintering-free incorporation
      of nanorods into the earth abundant hybrid glass composite, Young's modulus is
      enhanced by one to two orders of magnitude. This discovery, enabling reshaping
      control of plasmonic nanoparticles of multiple-length allows for continuous multi
      level recording and reading with a capacity over 10 terabytes with no appreciable
      change of the baseline over 600 years, which opens new opportunities for long
      data memory that affects the past and future.

PMID- 29568056
TI  - Repeatability and degree of territorial aggression differs among urban and rural
      great tits (Parus major).
AB  - Animals in urban habitats face many novel selection pressures such as increased
      human population densities and human disturbance. This is predicted to favour
      bolder and more aggressive individuals together with greater flexibility in
      behaviour. Previous work has focussed primarily on studying these traits in
      captive birds and has shown increased aggression and reduced consistency between
      traits (behavioural syndromes) in birds from urban populations. However,
      personality (consistency within a behavioural trait) has not been well studied in
      the wild. Here we tested whether urban free-living male great tits show greater
      territorial aggression than rural counterparts. We also tested predictions that
      both behavioural syndromes and personality would show lower consistency in urban
      populations. We found that urban populations were more aggressive than rural
      populations and urban birds appeared to show lower levels of individual
      behavioural repeatability (personality) as predicted. However, we found no effect
      of urbanisation on behavioural syndromes (correlations between multiple
      behavioural traits). Our results indicate that urban environments may favour
      individuals which exhibit increased territorial aggression and greater within
      trait flexibility which may be essential to success in holding urban territories.
      Determining how urban environments impact key fitness traits will be important in
      predicting how animals cope with ongoing urbanisation.

PMID- 29568057
TI  - Evidence that the Great Pacific Garbage Patch is rapidly accumulating plastic.
AB  - Ocean plastic can persist in sea surface waters, eventually accumulating in
      remote areas of the world's oceans. Here we characterise and quantify a major
      ocean plastic accumulation zone formed in subtropical waters between California
      and Hawaii: The Great Pacific Garbage Patch (GPGP). Our model, calibrated with
      data from multi-vessel and aircraft surveys, predicted at least 79 (45-129)
      thousand tonnes of ocean plastic are floating inside an area of 1.6 million km2;
      a figure four to sixteen times higher than previously reported. We explain this
      difference through the use of more robust methods to quantify larger debris. Over
      three-quarters of the GPGP mass was carried by debris larger than 5 cm and at
      least 46% was comprised of fishing nets. Microplastics accounted for 8% of the
      total mass but 94% of the estimated 1.8 (1.1-3.6) trillion pieces floating in the
      area. Plastic collected during our study has specific characteristics such as
      small surface-to-volume ratio, indicating that only certain types of debris have
      the capacity to persist and accumulate at the surface of the GPGP. Finally, our
      results suggest that ocean plastic pollution within the GPGP is increasing
      exponentially and at a faster rate than in surrounding waters.

PMID- 29568058
TI  - Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice
      with accumulation of aberrantly activated astrocytes.
AB  - There is compelling evidence that glial-immune interactions contribute to the
      progression of neurodegenerative diseases. The adaptive immune response has been
      implicated in disease processes of amyotrophic lateral sclerosis (ALS), but it
      remains unknown if innate immune signaling also contributes to ALS progression.
      Here we report that deficiency of the innate immune adaptor TIR domain-containing
      adaptor inducing interferon-beta (TRIF), which is essential for certain Toll-like
      receptor (TLR) signaling cascades, significantly shortens survival time and
      accelerates disease progression of ALS mice. While myeloid differentiation factor
      88 (MyD88) is also a crucial adaptor for most TLR signaling pathways, MyD88
      deficiency had only a marginal impact on disease course. Moreover, TRIF
      deficiency reduced the number of natural killer (NK), NK-T-lymphocytes, and CD8-T
      cells infiltrating into the spinal cord of ALS mice, but experimental modulation
      of these populations did not substantially influence survival time. Instead, we
      found that aberrantly activated astrocytes expressing Mac2, p62, and apoptotic
      markers were accumulated in the lesions of TRIF-deficient ALS mice, and that the
      number of aberrantly activated astrocytes was negatively correlated with survival
      time. These findings suggest that TRIF pathway plays an important role in
      protecting a microenvironment surrounding motor neurons by eliminating aberrantly
      activated astrocytes.

PMID- 29568059
TI  - Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP
      by microRNA-149-3p promotes aggressiveness of cancer cells.
AB  - The tumor suppressor DAB2IP contributes to modulate the network of information
      established between cancer cells and tumor microenvironment. Epigenetic and post
      transcriptional inactivation of this protein is commonly observed in multiple
      human malignancies, and can potentially favor progression of tumors driven by a
      variety of genetic mutations. Performing a high-throughput screening of a large
      collection of human microRNA mimics, we identified miR-149-3p as a negative post
      transcriptional modulator of DAB2IP. By efficiently downregulating DAB2IP, this
      miRNA enhances cancer cell motility and invasiveness, facilitating activation of
      NF-kB signaling and promoting expression of pro-inflammatory and pro-angiogenic
      factors. In addition, we found that miR-149-3p secreted by prostate cancer cells
      induces DAB2IP downregulation in recipient vascular endothelial cells,
      stimulating their proliferation and motility, thus potentially remodeling the
      tumor microenvironment. Finally, we found that inhibition of endogenous miR-149
      3p restores DAB2IP activity and efficiently reduces tumor growth and
      dissemination of malignant cells. These observations suggest that miR-149-3p can
      promote cancer progression via coordinated inhibition of DAB2IP in tumor cells
      and in stromal cells.

PMID- 29568060
TI  - Freestanding photocatalytic materials based on 3D graphene and polyporphyrins.
AB  - A new concept in the formulation of hybrid nanostructured materials combining
      high quality graphene 3D supported by Nickel foam and polyporphyrins for visible
      light photocatalytic application is here reported. Our innovative approach
      involves the development of a freestanding device able to: i) offer a high
      surface area to bind the photosensitizers by pi-pi interactions, and ii) enhance
      stability and photocatalytic efficiency by using cyclic porphyrin polymers. For
      these purposes, homo- and co-polymerization reactions by using different
      porphyrin (free or zinc complexed) monomers were performed. The microscopic
      structures and morphology of graphene polymer nanocomposites were investigated by
      using Scanning Electron Microscopy (SEM), X-ray photoelectron spectroscopy (XPS)
      and Atomic Force Microscopy (AFM). Finally, photocatalytic activity under visible
      light irradiation of the obtained nanocomposites was tested, by using methylene
      blue (MB) as organic pollutant. The obtained data suggested that hindered cyclic
      polymeric structures stacked on graphene surface by non-covalent interactions,
      restrict the formation of non photoactive aggregates and, as a consequence,
      induce an enhancement of photocatalytic activity. Remarkably, our systems show a
      degradation efficiency in the visible-light range much higher than other similar
      devices containing nanoporphyrin units reported in literature.

PMID- 29568061
TI  - An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein
      interactions and subcellular localizations.
AB  - Protein-protein interactions govern almost all cellular functions. These complex
      networks of stable and transient associations can be mapped by affinity
      purification mass spectrometry (AP-MS) and complementary proximity-based labeling
      methods such as BioID. To exploit the advantages of both strategies, we here
      design and optimize an integrated approach combining AP-MS and BioID in a single
      construct, which we term MAC-tag. We systematically apply the MAC-tag approach to
      18 subcellular and 3 sub-organelle localization markers, generating a molecular
      context database, which can be used to define a protein's molecular location. In
      addition, we show that combining the AP-MS and BioID results makes it possible to
      obtain interaction distances within a protein complex. Taken together, our
      integrated strategy enables the comprehensive mapping of the physical and
      functional interactions of proteins, defining their molecular context and
      improving our understanding of the cellular interactome.

PMID- 29568062
TI  - The membrane-distal regions of integrin alpha cytoplasmic domains contribute
      differently to integrin inside-out activation.
AB  - Functioning as signal receivers and transmitters, the integrin alpha/beta
      cytoplasmic tails (CT) are pivotal in integrin activation and signaling. 18 alpha
      integrin subunits share a conserved membrane-proximal region but have a highly
      diverse membrane-distal (MD) region at their CTs. Recent studies demonstrated
      that the presence of alpha CTMD region is essential for talin-induced integrin
      inside-out activation. However, it remains unknown whether the non-conserved
      alpha CTMD regions differently regulate the inside-out activation of integrin.
      Using alphaIIbbeta3, alphaLbeta2, and alpha5beta1 as model integrins and by
      replacing their alpha CTMD regions with those of alpha subunits that pair with
      beta3, beta2, and beta1 subunits, we analyzed the function of CTMD regions of 17
      alpha subunits in talin-mediated integrin activation. We found that the alpha
      CTMD regions play two roles on integrin, which are activation-supportive and
      activation-regulatory. The regulatory but not the supportive function depends on
      the sequence identity of alpha CTMD region. A membrane-proximal tyrosine residue
      present in the CTMD regions of a subset of alpha integrins was identified to
      negatively regulate integrin inside-out activation. Our study provides a useful
      resource for investigating the function of alpha integrin CTMD regions.

PMID- 29568063
TI  - Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate
      stromal fibroblasts and promotes BPH progression.
AB  - The activation of androgen receptor (AR) signaling plays an essential role in
      both prostate stromal cells and epithelial cells during the development of benign
      prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after
      5alpha-reductase inhibitor (5-ARI) treatment induced autophagy in prostate
      stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A
      expression was increased after androgen ablation, which facilitated autophagic
      flux development. Knockdown of ATG9A not only inhibited autophagy notably in
      prostate stromal fibroblasts, but also reduced the volumes of prostate stromal
      fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion,
      our findings suggested that ATG9A upregulation after long-term 5-ARI treatment
      constitutes a possible mechanism of BPH progression. Thus, combined treatment
      with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH
      progression.

PMID- 29568064
TI  - BPIFB1 (LPLUNC1) inhibits radioresistance in nasopharyngeal carcinoma by
      inhibiting VTN expression.
AB  - Bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1,
      previously named LPLUNC1) is highly expressed in the nasopharynx and
      significantly downregulated in nasopharyngeal carcinoma (NPC). Low expression is
      also associated with poor prognosis in patients with NPC. Radiotherapy is a
      routine treatment for NPC; however, radioresistance is a major cause of treatment
      failure. Thus, we aimed to investigate the role of BPIFB1 in the radioresponse of
      NPC. Colony formation and cell survival results showed that BPIFB1 sensitized NPC
      cells to ionizing radiation. VTN, a previously identified BPIFB1-binding protein,
      was shown to induce cell proliferation and survival, G2/M phase arrest, DNA
      repair, activation of the ATM-Chk2 and ATR-Chk1 pathways, and anti-apoptotic
      effects after exposure to radiation, facilitating NPC cell radioresistance.
      However, BPIFB1 inhibited this VTN-mediated radioresistance, ultimately improving
      NPC radiosensitivity. In conclusion, this study is the first to demonstrate the
      functions of BPIFB1 and VTN in the NPC radioresponse. Our findings indicated that
      promoting BPIFB1 expression and targeting VTN might represent new therapeutic
      strategies for NPC.

PMID- 29568065
TI  - A complete, homozygous CRX deletion causing nullizygosity is a new genetic
      mechanism for Leber congenital amaurosis.
AB  - CRX is a transcription factor required for activating the expression of many
      photoreceptor-neuron genes. CRX may be mutated in three forms of human blindness;
      Leber congenital amaurosis (LCA), cone-rod degeneration (CRD) and retinitis
      pigmentosa (RP). The pathogenic mechanism in most cases is likely dominant
      negative, with gain of function. We report a novel, complete homozygous CRX
      deletion in LCA. We identified a Lebanese family with 3 affected LCA cases. The
      proband was sequenced by NGS. Quantitative PCR, array comparative genomic
      hybridization, and long range PCR were performed. Full eye examinations, OCT and
      photography were performed. We identified a homozygous 56,000 bp deletion of CRX,
      which co-segregates and is heterozygous in four parents, who report normal
      vision. The blind children with LCA manifest severe retinal degeneration, a
      phenotype typical for CRX and LCA. We hypothesized that a single copy of CRX
      (haplo-insufficiency) in the causes mild abnormal foveal development, but not
      LCA. Two parents had significant inner and outer foveal and photoreceptor
      abnormalities. This is the first reported case of a homozygous, complete CRX
      deletion. Nullizygosity of CRX thus causes LCA while haplo-insufficiency of CRX
      causes abnormal foveal development, but not LCA. Our data suggest a new disease
      mechanism for CRX.

PMID- 29568066
TI  - Human transbodies that interfere with the functions of Ebola virus VP35 protein
      in genome replication and transcription and innate immune antagonism.
AB  - Small molecular inhibitors and passive immunization against Ebola virus disease
      (EVD) have been tested in animal models, including rodents and non-human
      primates, as well as in clinical trials. Nevertheless, there is currently no Food
      and Drug Administration (FDA)-approved therapy, and alternative strategies must
      be pursued. The aim of this study was to produce cell-penetrable human single
      chain antibodies (transbodies) that are able to interfere with the activities of
      interferon inhibitory domain (IID) of the VP35 protein, a multifunctional
      virulence factor of Ebola virus (EBOV). We speculated that effective VP35-IID
      specific transbodies could inspire further studies to identify an alternative to
      conventional antibody therapies. Phage display technology was used to generate
      Escherichia coli-derived human single-chain antibodies (HuscFvs) that bind to
      IID. HuscFvs were linked to nona-arginine (R9) to make them cell penetrable.
      Transbodies of transformed E. coli clones 13 and 3, which were predicted to
      interact with first basic patch residues (R9-HuscFv13), central basic patch, and
      end-cap residues (R9-HuscFv3), effectively inhibited EBOV minigenome activity.
      Transbodies of E. coli clones 3 and 8 antagonized VP35-mediated interferon
      suppression in VP35-transduced cells. We postulate that these transbodies formed
      an interface contact with the IID central basic patch, end-cap, and/or residues
      that are important for IID multimeric formation for dsRNA binding. These
      transbodies should be evaluated further in vitro using authentic EBOV and in vivo
      in animal models of EVD before their therapeutic/prophylactic effectiveness is
      clinically evaluated.

PMID- 29568067
TI  - A wide-band bio-chip for real-time optical detection of bioelectromagnetic
      interactions with cells.
AB  - The analytical and numerical design, implementation, and experimental validation
      of a new grounded closed coplanar waveguide for wide-band electromagnetic
      exposures of cells and their optical detection in real-time is reported. The
      realized device fulfills high-quality requirements for novel bioelectromagnetic
      experiments, involving elevated temporal and spatial resolutions. Excellent
      performances in terms of matching bandwidth (less than -10 dB up to at least 3
      GHz), emission (below 1 * 10-6 W/m2) and efficiency (around 1) have been obtained
      as revealed by both numerical simulations and experimental measurements. A low
      spatial electric field inhomogeneity (coefficient of variation of around 10 %)
      has been achieved within the cell solutions filling the polydimethylsiloxane
      reservoir of the conceived device. This original bio-chip based on the grounded
      closed coplanar waveguide concept opens new possibilities for the development of
      controlled experiments combining electromagnetic exposures and sophisticated
      imaging using optical spectroscopic techniques.

PMID- 29568068
TI  - Identification of p38 MAPK as a novel therapeutic target for Friedreich's ataxia.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative
      disorder caused by decreased expression of frataxin, a protein that localizes to
      mitochondria and is critical for iron-sulfur-cluster (ISC) assembly. There are no
      proven effective treatments for FRDA. We previously screened a random shRNA
      library and identified a synthetic shRNA (gFA11) that reverses the growth defect
      of FRDA cells in culture. We now report that gFA11 decreases cytokine secretion
      in primary FRDA fibroblasts and reverts other changes associated with cell
      senescence. The gene-expression profile induced by gFA11 is remarkably similar to
      the gene-expression profile induced by the p38 MAPK inhibitor SB203580. We found
      that p38 phosphorylation, indicating activation of the p38 pathway, is higher in
      FRDA cells than in normal control cells, and that siRNA knockdown of frataxin in
      normal fibroblasts also increases p38 phosphorylation. Treatment of FRDA cells
      with p38 inhibitors recapitulates the reversal of the slow-growth phenotype
      induced by clone gFA11. These data highlight the involvement of the p38 MAPK
      pathway in the pathogenesis of FRDA and the potential use of p38 inhibitors as a
      treatment for FRDA.

PMID- 29568069
TI  - Rapid and damage-free outgassing of implanted helium from amorphous silicon
      oxycarbide.
AB  - Damage caused by implanted helium (He) is a major concern for material
      performance in future nuclear reactors. We use a combination of experiments and
      modeling to demonstrate that amorphous silicon oxycarbide (SiOC) is immune to He
      induced damage. By contrast with other solids, where implanted He becomes
      immobilized in nanometer-scale precipitates, He in SiOC remains in solution and
      outgasses from the material via atomic-scale diffusion without damaging its free
      surfaces. Furthermore, the behavior of He in SiOC is not sensitive to the exact
      concentration of carbon and hydrogen in this material, indicating that the
      composition of SiOC may be tuned to optimize other properties without
      compromising resistance to implanted He.

PMID- 29568070
TI  - Spindle cell sarcoma: a SEER population-based analysis.
AB  - Due to the substantial limitation of study population, Spindle cell sarcoma (SCS)
      was unexplored comprehensively. In this study, we investigated the clinical
      characteristics and disease specific prognostic factors of SCS. 3299 SCS cases
      were identified and extracted from Surveillance, Epidemiology, and End Results
      (SEER) database (1973-2017). White people account for 79.1% with median age of 57
      years without predominance in any gender. Significant disease specific survival
      (DSS) and overall survival (OS) were found differentiated in age, T stage, N
      stage, M stage, AJCC stage, SEER historic stage, tumor locations, surgery, and
      pathologic grade. In the multivariate Cox analysis, the age >64 years (for DSS, P
      < 0.001 and for OS, P < 0.001; Reference age <=64 years), AJCC stage III (for
      DSS, P = 0.006 and for OS, P = 0.04; Reference: AJCC stage I), and non-surgical
      treatment (for DSS, P < 0.001 and for OS, P < 0.001; Reference: surgery) were
      independently associated with worse DSS and OS. In brief, our study demonstrated
      that SCS mostly found in white people at fifth to seventh decades of life without
      gender predilection. The patient's age, AJCC stage, tumor location and surgery
      were independent prognostic indicators for both DSS and OS of SCS.

PMID- 29568071
TI  - Author Correction: Dynamics of RIF1 SUMOylation is regulated by PIAS4 in the
      maintenance of Genomic Stability.
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- 29568072
TI  - Regulation of synaptic architecture and synaptic vesicle pools by Nervous wreck
      at Drosophila Type 1b glutamatergic synapses.
AB  - Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses
      that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the
      human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal
      microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones
      (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both
      exocytosis and endocytosis components. Results from an electron microscopic (EM)
      analysis showed that Nwk proteins localized at synaptic edges and in SV pools.
      Both the synaptic areas and the number of SVs in the readily releasable (RRPs)
      and reserve (RPs) SV pools in nwk2 were significantly reduced. Synergistic,
      morphological phenotypes observed from eag1;;nwk2 neuromuscular junctions
      suggested that Nwk may regulate synaptic plasticity differently from activity
      dependent Hebbian plasticity. Although the synaptic areas in eag1;;nwk2 boutons
      were not significantly different from those of nwk2, the number of SVs in the
      RRPs was similar to those of Canton-S. In addition, three-dimensional, high
      voltage EM tomographic analysis demonstrated that significantly fewer enlarged
      SVs were present in nwk2 RRPs. Furthermore, Nwk formed protein complexes with
      Drosophila Synapsin and Synaptotagmin 1 (DSypt1). Taken together, these findings
      suggest that Nwk is able to maintain synaptic architecture and both SV size and
      distribution at T-AZs by interacting with Synapsin and DSypt1.

PMID- 29568073
TI  - Interrupting oral infection of Porphyromonas gingivalis with anti-FimA antibody
      attenuates bacterial dissemination to the arthritic joint and improves
      experimental arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically results
      in strong inflammation and bone destruction in the joints. It is generally known
      that the pathogenesis of RA is linked to cardiovascular and periodontal diseases.
      Though rheumatoid arthritis and periodontitis share many pathologic features such
      as a perpetual inflammation and bone destruction, the precise mechanism
      underlying a link between these two diseases has not been fully elucidated.
      Collagen-induced arthritis (CIA) mice were orally infected with Porphyromonas
      gingivalis (Pg) or Pg preincubated with an anti-FimA antibody (FimA Ab) specific
      for fimbriae that are flexible appendages on the cell surface. Pg-infected CIA
      mice showed oral microbiota disruption and increased alveolar bone loss and had
      synovitis and joint bone destruction. However, preincubation with FimA Ab led to
      a significant reduction in the severity of both oral disease and arthritis.
      Moreover, FimA Ab attenuated bacterial attachment and aggregation on human
      gingival and rheumatoid arthritis synovial fibroblasts. In addition, we
      discovered bacteria may utilize dendritic cells, macrophages and neutrophils to
      migrate into the joints of CIA mice. These results suggest that disrupting Pg
      fimbriae function by FimA Ab ameliorates RA.

PMID- 29568074
TI  - Intrahippocampal injection of a lentiviral vector expressing neurogranin enhances
      cognitive function in 5XFAD mice.
AB  - Progressive cognitive declines are the main clinical symptoms of Alzheimer's
      disease (AD). Cognitive impairment in AD is directly correlated with amyloid beta
      (Abeta)-mediated synaptic deficits. It is known that upregulation of neurogranin
      (Ng), a postsynaptic protein, contributes to the enhancement of synaptic
      plasticity and cognitive function. By contrast, downregulation of Ng expression
      results in learning and memory impairments. Interestingly, Ng expression is
      significantly reduced in the parenchyma of brains with AD. However, the
      pathological role that downregulated Ng plays in the cognitive dysfunctions
      observed in AD remains unclear. Therefore, the present study examined whether
      enhancing Ng expression affected cognitive functions in 5XFAD mice, an animal
      model of AD. We found that the Ng reductions and cognitive decline observed in
      5XFAD mice were restored in mice that were intrahippocampally injected with an Ng
      expressing lentiviral vector. Furthermore, overexpression of Ng upregulated
      expression of postsynaptic density protein-95 in the hippocampus of 5XFAD mice.
      These results suggest that the cause of cognitive decline in AD may be at least
      partially associated with reduced Ng levels, and thus, supplementation of Ng may
      be an appropriate therapeutic strategy for individuals with AD.

PMID- 29568075
TI  - Inhibition of endothelial nitric oxide synthase reverses the effect of exercise
      on improving cognitive function in hypertensive rats.
AB  - Hypertension-induced endothelial dysfunction is associated with beta-amyloid
      (Abeta) deposition, a typical pathology of Alzheimer's disease (AD). Endothelial
      nitric oxide synthase (eNOS) phosphorylation, impaired by phosphatidylinositol 3
      kinase (PI3K)/protein kinase-B(Akt) pathway abnormalities in hypertensive rats,
      has a critical role in endothelial function. However, it is unknown whether eNOS
      participates in the hypertension-induced pathology of AD. In this study, we
      investigated the role of eNOS in Abeta deposition and cognitive function in
      stroke-prone spontaneously hypertensive (SHRSP) rats. Physical exercise was used
      as a promoter, and Nomega-nitro L-arginine methyl ester (L-NAME) was used as an
      inhibitor of eNOS to determine the effects of eNOS on SHRSP rats. Compared with
      Wistar Kyoto (WKY) rats, the hypertensive challenge caused cognitive impairment,
      decreased eNOS levels and increased amyloid precursor protein (APP), beta
      secretase, and Abeta levels in the cortex and hippocampus. Sixteen weeks of
      exercise lowered blood pressure (BP), promoted eNOS expression, ameliorated
      Alzheimer's pathology, and improved cognitive function in 29-week-old SHRSP rats.
      Furthermore, daily treatment with L-NAME reversed the beneficial effects of
      exercise on SHRSP rats. Exercise also decreased the protein levels of insulin
      like growth factor-1 (IGF-1), PI3K, and phospho-Akt (p-Akt, ser473). In addition,
      long-term exercise increased the expression levels of IGF-1, PI3K, and p-Akt
      (ser473) in the brains of SHRSP rats. In conclusion, eNOS downregulation
      contributed to hypertension-induced Alzheimer pathology and cognitive impairment.
      Long-term exercise initiated in rats at a young age promoted eNOS expression and
      attenuated vascular-related Alzheimer's pathology via the IGF-1/PI3K/p-Akt
      pathway in SHRSP rats.

PMID- 29568076
TI  - Author Correction: The responses of cancer cells to PLK1 inhibitors reveal a
      novel protective role for p53 in maintaining centrosome separation.
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- 29568077
TI  - Cellular response to persistent foot-and-mouth disease virus infection is linked
      to specific types of alterations in the host cell transcriptome.
AB  - Food-and-mouth disease virus (FMDV) is a highly contagious virus that seriously
      threatens the development of animal husbandry. Although persistent FMDV infection
      can dramatically worsen the situation, the mechanisms involved in persistent FMDV
      infection remain unclear. In the present study, we identified the presence of
      evolved cells in the persistently FMDV-infected cell line. These cells exhibited
      resistance to the parent FMDV and re-established persistent infection when
      infected with FMDV-Op (virus supernatant of persistent infection cell lines),
      emphasizing the decisive role of evolved host cells in the establishment of
      persistent FMDV infection. Using RNA-seq, we identified the gene expression
      profiles of these evolved host cells. In total, 4,686 genes were differentially
      expressed in evolved cells compared with normal cells, with these genes being
      involved in metabolic processes, cell cycle, and cellular protein catabolic
      processes. In addition, 1,229 alternative splicing events, especially skipped
      exon events, were induced in evolved cells. Moreover, evolved cells exhibited a
      stronger immune defensive response and weaker MAPK signal response than normal
      cells. This comprehensive transcriptome analysis of evolved host cells lays the
      foundation for further investigations of the molecular mechanisms of persistent
      FMDV infection and screening for genes resistant to FMDV infection.

PMID- 29568078
TI  - Taurine protects dopaminergic neurons in a mouse Parkinson's disease model
      through inhibition of microglial M1 polarization.
AB  - Microglia-mediated neuroinflammation is implicated in multiple neurodegenerative
      disorders, including Parkinson's disease (PD). Hence, the modulatioein of
      sustained microglial activation may have therapeutic potential. This study is
      designed to test the neuroprotective efficacy of taurine, a major intracellular
      free beta-amino acid in mammalian tissues, by using paraquat and maneb-induced PD
      model. Results showed that mice intoxicated with paraquat and maneb displayed
      progressive dopaminergic neurodegeneration and motor deficits, which was
      significantly ameliorated by taurine. Taurine also attenuated the aggregation of
      alpha-synuclein in paraquat and maneb-intoxicated mice. Mechanistically, taurine
      suppressed paraquat and maneb-induced microglial activation. Moreover, depletion
      of microglia abrogated the dopaminergic neuroprotective effects of taurine,
      revealing the role of microglial activation in taurine-afforded neuroprotection.
      Subsequently, we found that taurine suppressed paraquat and maneb-induced
      microglial M1 polarization and gene expression levels of proinflammatory factors.
      Furthermore, taurine was shown to be able to inhibit the activation of NADPH
      oxidase (NOX2) by interfering with membrane translocation of cytosolic subunit,
      p47phox and nuclear factor-kappa B (NF-kappaB) pathway, two key factors for the
      initiation and maintenance of M1 microglial inflammatory response. Altogether,
      our results showed that taurine exerted dopaminergic neuroprotection through
      inactivation of microglia-mediated neuroinflammation, providing a promising
      avenue and candidate for the potential therapy for patients suffering from PD.

PMID- 29568079
TI  - Pattern Formation through Temporal Fractional Derivatives.
AB  - It is well known that temporal first-derivative reaction-diffusion systems can
      produce various fascinating Turing patterns. However, it has been found that many
      physical, chemical and biological systems are well described by temporal
      fractional-derivative reaction-diffusion equations. Naturally arises an issue
      whether and how spatial patterns form for such a kind of systems. To address this
      issue clearly, we consider a classical prey-predator diffusive model with the
      Holling II functional response, where temporal fractional derivatives are
      introduced according to the memory character of prey's and predator's behaviors.
      In this paper, we show that this fractional-derivative system can form steadily
      spatial patterns even though its first-derivative counterpart can't exhibit any
      steady pattern. This result implies that the temporal fractional derivatives can
      induce spatial patterns, which enriches the current mechanisms of pattern
      formation.

PMID- 29568080
TI  - Studying an antiaromatic polycyclic hydrocarbon adsorbed on different surfaces.
AB  - Antiaromatic and open-shell molecules are attractive because of their distinct
      electronic and magnetic behaviour. However, their increased reactivity creates a
      challenge for probing their properties. Here, we describe the on-surface and in
      solution generation and characterisation of a highly reactive antiaromatic
      molecule: indeno[1,2-b]fluorene (IF). In solution, we generated IF by KI-induced
      dehalogenation of a dibromo-substituted precursor molecule and found that IF
      survives for minutes at ambient conditions. Using atom manipulation at low
      temperatures we generated IF on Cu(111) and on bilayer NaCl. On these surfaces,
      we characterised IF by bond-order analysis using non-contact atomic force
      microscopy with CO-functionalised tips and by orbital imaging using scanning
      tunnelling microscopy. We found that the closed-shell configuration and
      antiaromatic character predicted for gas-phase IF are preserved on the NaCl film.
      On Cu(111), we observed significant bond-order reorganisation within the s
      indacene moiety because of chemisorption, highlighting the importance of molecule
      surface interactions on the pi-electron distribution.

PMID- 29568082
TI  - Antioxidant and prebiotic activity of five peonidin-based anthocyanins extracted
      from purple sweet potato (Ipomoea batatas (L.) Lam.).
AB  - Twelve kinds of anthocyanins from the Chinese purple sweet potato cultivar
      (Ipomoea batatas (L.) Lam.) were extracted and identified using LC-MS/MS, which
      had a high content of peonidin-based anthocyanins. Five peonidin-based
      anthocyanin monomers (P1, P2, P3, P4 and P5) were isolated by preparative liquid
      chromatography with structural analyses using an Impact II Q-TOF MS/MS. Then, the
      functional properties of the anthocyanin monomers, such as the antioxidant
      activities, proliferative effects on probiotics, and their inhibition on harmful
      bacteria in vitro, were investigated. The peonidin-based components in purple
      sweet potato anthocyanins (PSPAs) showed good properties regarding scavenging 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide anions, and had good
      potential in reducing the total power activity and Fe2+ chelating ability. While
      the order of the antioxidant abilities was as follows: P4 > P5 > P3 > P2 > P1 >
      PSPAs. Microbial cultivations showed that P1, P2, P3, P4, P5 and PSPAs could
      induce the proliferation of Bifidobacterium bifidum, Bifidobacterium
      adolescentis, Bifidobacterium infantis and Lactobacillus acidophilus, and they
      inhibited the growth of Staphylococcus aureus and Salmonella typhimurium,
      suggesting the anthocyanins might have prebiotic-like activity through the
      modulation of the intestinal microbiota. Our results indicate that peonidin-based
      anthocyanins could be further utilized in health foods and pharmaceutical
      developments.

PMID- 29568081
TI  - An integrated flow cytometry-based platform for isolation and molecular
      characterization of circulating tumor single cells and clusters.
AB  - Comprehensive molecular analysis of rare circulating tumor cells (CTCs) and cell
      clusters is often hampered by low throughput and purity, as well as cell loss. To
      address this, we developed a fully integrated platform for flow cytometry-based
      isolation of CTCs and clusters from blood that can be combined with whole
      transcriptome analysis or targeted RNA transcript quantification. Downstream
      molecular signature can be linked to cell phenotype through index sorting. This
      newly developed platform utilizes in-line magnetic particle-based leukocyte
      depletion, and acoustic cell focusing and washing to achieve >98% reduction of
      blood cells and non-cellular debris, along with >1.5 log-fold enrichment of
      spiked tumor cells. We could also detect 1 spiked-in tumor cell in 1 million WBCs
      in 4/7 replicates. Importantly, the use of a large 200MUm nozzle and low sheath
      pressure (3.5 psi) minimized shear forces, thereby maintaining cell viability and
      integrity while allowing for simultaneous recovery of single cells and clusters
      from blood. As proof of principle, we isolated and transcriptionally
      characterized 63 single CTCs from a genetically engineered pancreatic cancer
      mouse model (n = 12 mice) and, using index sorting, were able to identify
      distinct epithelial and mesenchymal sub-populations based on linked single cell
      protein and gene expression.

PMID- 29568083
TI  - Identification of highly effective target genes for RNAi-mediated control of
      emerald ash borer, Agrilus planipennis.
AB  - Recent study has shown that RNA interference (RNAi) is efficient in emerald ash
      borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA
      (dsRNA) targeting specific genes causes gene silencing and mortality in neonates.
      Here, we report on the identification of highly effective target genes for RNAi
      mediated control of EAB. We screened 13 candidate genes in neonate larvae and
      selected the most effective target genes for further investigation, including
      their effect on EAB adults and on a non-target organism, Tribolium castaneum. The
      two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate
      3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB
      eggs, larvae, and adults, the hsp is expressed at higher levels when compared to
      that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae
      and adults. Administration of a mixture of both dsRNAs worked better than either
      dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause
      mortality in T. castaneum. Thus, the two genes identified cause high mortality in
      the EAB with no apparent phenotype effects in a non-target organism, the red
      flour beetle, and could be used in RNAi-mediated control of this invasive pest.

PMID- 29568085
TI  - Author Correction: A Flexible Electret Membrane with Persistent Electrostatic
      Effect and Resistance to Harsh Environment for Energy Harvesting.
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- 29568084
TI  - Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived
      from the Human Placenta and Umbilical Cord.
AB  - Mesenchymal stem/stromal cells (MSCs) derived from placental tissue show great
      therapeutic potential and have been used in medical treatment, but the similarity
      and differences between the MSCs derived from various parts of the placenta
      remain unclear. In this study, we compared MSCs derived from different perinatal
      tissues, including the umbilical cord (UC), amniotic membrane (AM), chorionic
      plate (CP) and decidua parietalis (DP). Using human leukocyte antigen (HLA)
      typing and karyotype analysis, we found that the first three cell types were
      derived from the foetus, while the MSCs from the decidua parietalis were derived
      from the maternal portion of the placental tissue. Our results indicate that both
      foetal and maternal MSCs share a similar phenotype and multi-lineage
      differentiation potential, but foetal MSCs show a significantly higher expansion
      capacity than do maternal MSCs. Furthermore, MSCs from all sources showed
      significant differences in the levels of several paracrine factors.

PMID- 29568086
TI  - Quantifying the propagation of distress and mental disorders in social networks.
AB  - Heterogeneity of human beings leads to think and react differently to social
      phenomena. Awareness and homophily drive people to weigh interactions in social
      multiplex networks, influencing a potential contagion effect. To quantify the
      impact of heterogeneity on spreading dynamics, we propose a model of coevolution
      of social contagion and awareness, through the introduction of statistical
      estimators, in a weighted multiplex network. Multiplexity of networked
      individuals may trigger propagation enough to produce effects among vulnerable
      subjects experiencing distress, mental disorder, which represent some of the
      strongest predictors of suicidal behaviours. The exposure to suicide is
      emotionally harmful, since talking about it may give support or inadvertently
      promote it. To disclose the complex effect of the overlapping awareness on
      suicidal ideation spreading among disordered people, we also introduce a data
      driven approach by integrating different types of data. Our modelling approach
      unveils the relationship between distress and mental disorders propagation and
      suicidal ideation spreading, shedding light on the role of awareness in a social
      network for suicide prevention. The proposed model is able to quantify the impact
      of overlapping awareness on suicidal ideation spreading and our findings
      demonstrate that it plays a dual role on contagion, either reinforcing or
      delaying the contagion outbreak.

PMID- 29568087
TI  - Comparative study of afterpulsing behavior and models in single photon counting
      avalanche photo diode detectors.
AB  - Single-photon avalanche diode (SPAD) detectors, have a great importance in fields
      like quantum key distribution, laser ranging, florescence microscopy, etc.
      Afterpulsing is a non-ideal behavior of SPADs that adversely affects any
      application that measures the number or timing of detection events. Several
      studies based on a few individual detectors, derived distinct mathematical models
      from semiconductor physics perspectives. With a consistent testing procedure and
      statistically large data sets, we show that different individual detectors - even
      if identical in type, make, brand, etc. - behave according to fundamentally
      different mathematical models. Thus, every detector must be characterized
      individually and it is wrong to draw universal conclusions about the physical
      meaning behind these models. We also report the presence of high-order
      afterpulses that are not accounted for in any of the standard models.

PMID- 29568089
TI  - The importance of bone marrow examination in patients with light chain
      amyloidosis achieving a complete response.

PMID- 29568090
TI  - IDH1R132, IDH2R140 and IDH2R172 in AML: different genetic landscapes correlate
      with outcome and may influence targeted treatment strategies.

PMID- 29568088
TI  - Transcription factor PAX6 as a novel prognostic factor and putative tumour
      suppressor in non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths. Novel predictive biomarkers
      are needed to improve treatment selection and more accurate prognostication. PAX6
      is a transcription factor with a proposed tumour suppressor function.
      Immunohistochemical staining was performed on tissue microarrays from 335 non
      small cell lung cancer (NSCLC) patients for PAX6. Multivariate analyses of
      clinico-pathological variables and disease-specific survival (DSS) was carried
      out, and phenotypic changes of two NSCLC cell lines with knockdown of PAX6 were
      characterized. While PAX6 expression was only associated with a trend of better
      disease-specific survival (DSS) (p = 0.10), the pN+ subgroup (N = 103) showed
      significant correlation between high PAX6 expression and longer DSS (p = 0.022).
      Median survival for pN + patients with high PAX6 expression was 127.4 months,
      versus 22.9 months for patients with low PAX6 expression. In NCI-H661 cells,
      knockdown of PAX6 strongly activated serum-stimulated migration. In NCI-H460
      cells, PAX6 knockdown activated anchorage-independent growth. We did not observe
      any significant effect of PAX6 on proliferation in either of cell lines. Our
      findings strongly support the proposition of PAX6 as a valid and positive
      prognostic marker in NSCLC in node-positive patients. There is a need for further
      studies, which should provide mechanistical explanation for the role of PAX6 in
      NSCLC.

PMID- 29568091
TI  - Sex and degree of severity influence the prognostic impact of anemia in primary
      myelofibrosis: analysis based on 1109 consecutive patients.

PMID- 29568092
TI  - Prognostic significance of interphase FISH in monoclonal gammopathy of
      undetermined significance.

PMID- 29568093
TI  - Selective inhibition of leukemia-associated SHP2E69K mutant by the allosteric
      SHP2 inhibitor SHP099.

PMID- 29568094
TI  - Whole-exome sequencing reveals acquisition of mutations leading to the onset of
      donor cell leukemia after hematopoietic transplantation: a model of
      leukemogenesis.

PMID- 29568095
TI  - Genomic profiling reveals spatial intra-tumor heterogeneity in follicular
      lymphoma.

PMID- 29568096
TI  - The -2518 A/G polymorphism of the monocyte chemoattractant protein-1 as a
      candidate genetic predisposition factor for secondary myelofibrosis and biomarker
      of disease severity.

PMID- 29568097
TI  - Minimal residual disease (MRD) monitoring and mutational landscape in AML with
      RUNX1-RUNX1T1: a study on 134 patients.

PMID- 29568098
TI  - Association between response kinetics and outcomes in relapsed/refractory
      multiple myeloma: analysis from TOURMALINE-MM1.

PMID- 29568099
TI  - Identification of a novel CPSF6-RARG fusion transcript in acute myeloid leukemia
      resembling acute promyelocytic leukemia.

PMID- 29568100
TI  - Effects of an antenatal dietary intervention in overweight and obese women on 6
      month infant outcomes: follow-up from the LIMIT randomised trial.
AB  - BACKGROUND: The immediate impact of providing an antenatal dietary intervention
      during pregnancy has been extensively studied, but little is known of the effects
      beyond the neonatal period. Our objective was to evaluate the effect of an
      antenatal dietary intervention in overweight or obese women on infant outcomes 6
      months after birth. METHODS: We conducted a follow up study of infants born to
      women who participated in the LIMIT trial during pregnancy. Live-born infants at
      6-months of age, and whose mother provided consent to ongoing follow-up were
      eligible. The primary follow-up study endpoint was the incidence of infant BMI z
      score >=90th centile for infant sex and age. Secondary study outcomes included a
      range of infant anthropometric measures, neurodevelopment, general health, and
      infant feeding. Analyses used intention to treat principles according to the
      treatment group allocated in pregnancy. Missing data were imputed and analyses
      adjusted for maternal early pregnancy BMI, parity, study centre, socioeconomic
      status, age, and smoking status. Outcome assessors were blinded to the allocated
      treatment group. RESULTS: A total of 1754 infants were assessed at age 6 months
      (Lifestyle Advice n = 869; Standard Care n = 885), representing 82.1% of the
      eligible sample (n = 2136). There were no statistically significant differences
      in the incidence of infant BMI z-score >=90th centile for infants born to women
      in the Lifestyle Advice group, compared with the Standard Care group (Lifestyle
      Advice 233 (21.71%) vs. Standard Care 233 (21.90%); adjusted relative risk (aRR)
      0.99; 95% confidence interval 0.82 to 1.18; p = 0.88). There were no other
      effects on infant growth, adiposity, or neurodevelopment. CONCLUSION: Providing
      pregnant women who were overweight or obese with an antenatal dietary and
      lifestyle intervention did not alter 6-month infant growth and adiposity. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      (ACTRN12607000161426).

PMID- 29568101
TI  - CYP2A6 is associated with obesity: studies in human samples and a high fat diet
      mouse model.
AB  - BACKGROUND/OBJECTIVES: CYP2A6 (CYP2A5 in mice) is mainly expressed in the liver.
      Hepatic CYP2A6 expression is increased in patients with non-alcoholic fatty liver
      disease (NAFLD). In mice, hepatic CYP2A5 is induced by high fat diet (HFD)
      feeding. Hepatic CYP2A5 is also increased in monosodium glutamate-induced obese
      mice. NAFLD is associated with obesity. In this study, we examined whether
      obesity is related to CYP2A6. SUBJECTS/METHODS: Obesity genetic association
      study: The SAGE is a comprehensive genome-wide association study (GWAS) with case
      subjects having a lifetime history of alcohol dependence and control subjects
      never addicted to alcohol. We used 1030 control individuals with self-reported
      height and weight. A total of 12 single nucleotide polymorphisms (SNP) within the
      CYP2A6 gene were available. Obesity was determined as a BMI >=30: 30-34.9 (Class
      I obesity) and >=35 (Class II and III obesity). Animal experiment study: CYP2A5
      knockout (cyp2a5 -/- ) mice and wild type (cyp2a5 +/+ ) mice were fed HFD for 14
      weeks. Body weight was measured weekly. After an overnight fast, the mice were
      sacrificed. Liver and blood were collected for biochemical assays. RESULTS:
      Single marker analysis showed that three SNPs (rs8192729, rs7256108, and
      rs7255443) were associated with class I obesity (p < 0.05). The most significant
      SNP for obesity was rs8192729 (odds ratio (OR) = 1.94, 95% confidence intervals =
      1.21-3.10, p = 0.00582). After HFD feeding, body weight was increased in cyp2a5 
      /- mice to a greater extent than in cyp2a5 +/+ mice, and fatty liver was more
      pronounced in cyp2a5 -/- mice than in cyp2a5 +/+ mice. PPARalpha deficiency in
      cyp2a5 -/- mice developed more severe fatty liver, but body weight was not
      increased significantly. CONCLUSION: CYP2A6 is associated with human obesity;
      CYP2A5 protects against obesity and NAFLD in mice. PPARalpha contributes to the
      CYP2A5 protective effects on fatty liver but it opposes to the protective effects
      on obesity.

PMID- 29568102
TI  - Enhanced hexose-6-phosphate dehydrogenase expression in adipose tissue may
      contribute to diet-induced visceral adiposity.
AB  - BACKGROUND: Visceral fat accumulation increases the risk of developing type 2
      diabetes and metabolic syndrome, and is associated with excessive glucocorticoids
      (GCs). Fat depot-specific GC action is tightly controlled by 11beta
      hydroxysteroid dehydrogenase (11beta-HSD1) coupled with the enzyme hexose-6
      phosphate dehydrogenase (H6PDH). Mice with inactivation or activation of H6PDH
      genes show altered adipose 11beta-HSD1 activity and lipid storage. We
      hypothesized that adipose tissue H6PDH activation is a leading cause for the
      visceral obesity and insulin resistance. Here, we explored the role and possible
      mechanism of enhancing adipose H6PDH in the development of visceral adiposity in
      vivo. METHODS: We investigated the potential contribution of adipose H6PDH
      activation to the accumulation of visceral fat by characterization of visceral
      fat obese gene expression profiles, fat distribution, adipocyte metabolic
      molecules, and abdominal fat-specific GC signaling mechanisms underlying the diet
      induced visceral obesity and insulin resistance in H6PDH transgenic mice fed a
      standard of high-fat diet (HFD). RESULTS: Transgenic H6PDH mice display increased
      abdominal fat accumulation, which is paralleled by elevated lipid synthesis
      associated with induction of lipogenic transcriptor C/EBPalpha and PPARgamma mRNA
      levels within adipose tissue. Transgenic H6PDH mice fed a high-fat diet (HFD)
      gained more abdominal visceral fat mass coupled with activation of GSK3beta and
      induction of XBP1/IRE1alpha, but reduced pThr308 Akt/PKB content and browning
      gene CD137 and GLUT4 mRNA levels within the visceral adipose tissue than WT
      controls. HFD-fed H6PDH transgenic mice also had impaired insulin sensitivity and
      exhibited elevated levels of intra-adipose GCs with induction of adipose 11beta
      HSD1. CONCLUSION: These data provide the first in vivo mechanistic evidence for
      the adverse metabolic effects of adipose H6PDH activation on visceral fat
      distribution, fat metabolism, and adipocyte function through enhancing 11beta
      HSD1-driven intra-adipose GC action.

PMID- 29568103
TI  - Incidence of end-stage renal disease following bariatric surgery in the Swedish
      Obese Subjects Study.
AB  - BACKGROUND: Obesity is a major public health problem leading to co-morbidities
      such as diabetes, hypertension and kidney failure. Bariatric surgery results in
      pronounced and maintained weight loss and prevention of obesity-related diseases
      and their complications. Most studies of bariatric surgery on kidney disease show
      improvements after surgery. However, long-term studies analyzing hard end-points
      are lacking. Here we report on the long-term effects of bariatric surgery
      compared to usual obesity care on incidence of end-stage renal disease (ESRD)
      alone and in combination with chronic kidney disease stage 4 (CKD4/ESRD).
      METHODS: 4047 patients were included in the Swedish Obese Subjects (SOS) study.
      Inclusion criteria were age 37-60 years and BMI >= 34 in men and BMI >= 38 in
      women. Patients in the bariatric surgery group (N = 2010) underwent banding
      (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls (N =
      2037) received usual obesity care. In this analysis, patients were followed up
      for a median time of 18 years. The incidence of ESRD and CKD4 was obtained by
      crosschecking the SOS database with the Swedish National Patient Register.
      RESULTS: During follow-up, ESRD occurred in 13 patients in the surgery group and
      in 26 patients in the control group (adjusted hazard ratio (HR) = 0.27; 95% CI
      0.12-0.60; p = 0.001). The number of CKD4/ESRD events was 23 in the surgery group
      and 39 in the control group (adjusted HR = 0.33; 95% CI 0.18-0.62; p < 0.001). In
      both analyses, bariatric surgery had a more favorable effect in patients with
      baseline serum insulin levels above median compared to those with lower insulin
      levels (interaction p = 0.010). Treatment benefit of bariatric surgery was also
      greater in patients with macroalbuminuria at baseline compared to those without
      macroalbuminuria (interaction p < 0.001). CONCLUSIONS: Our study showed for the
      first time that bariatric surgery is associated with a long-term protection
      against ESRD and CKD4/ESRD.

PMID- 29568104
TI  - Gut-microbiome-related LCT genotype and 2-year changes in body composition and
      fat distribution: the POUNDS Lost Trial.
AB  - BACKGROUND/OBJECTIVES: Gut microbiome regulates host energy metabolism and
      adiposity. A recent study identified a genome-wide significant variant in the
      lactase (LCT) gene that determines gut-microbiome abundance. We investigated
      whether the LCT variant influenced long-term changes in adiposity among
      overweight and obese individuals. SUBJECTS/METHODS: We included 583 whites with
      LCT variant rs4988235 (G allele as Bifidobacterium-abundance-increasing allele)
      who were randomly assigned to one of four weight-loss diets varying in
      macronutrient contents. Two-year changes in adiposity measures were assessed
      according to the LCT genotype and weight-loss diets. RESULTS: We observed a
      significant interaction between the LCT genotype and dietary protein intake on
      changes in whole body total fat mass %, trunk fat %, superficial adipose tissue
      mass (SAT), visceral adipose tissue mass (VAT), and total adipose tissue mass
      (TAT) (Pinteraction < 0.05 for all). In response to high-protein diet, carrying
      the G allele of LCT variant rs4988235 was associated with greater reduction of
      whole body total fat mass % (beta [SE] -0.9 [0.43], P = 0.04), trunk fat % (-1.06
      [0.58], P = 0.07), SAT (-0.89 [0.42], P = 0.04), VAT (-0.63 [0.27], P = 0.03),
      and TAT (-1.69 [0.76], P = 0.03). Conversely, increasing numbers of the G allele
      tended to be related to less reduction of these outcomes in response to low
      protein diet. CONCLUSIONS: Long-term improvement of body fat composition and
      distribution was significantly influenced by the Bifidobacterium-related LCT
      genotype and dietary protein intake. Overweight and obese individuals with the G
      allele of LCT variant rs4988235 may benefit improving adiposity by eating a low
      calorie, high-protein diet.

PMID- 29568105
TI  - Early childhood BMI trajectories in monogenic obesity due to leptin, leptin
      receptor, and melanocortin 4 receptor deficiency.
AB  - OBJECTIVE: To evaluate whether early childhood body mass index (BMI) is an
      appropriate indicator for monogenic obesity. METHODS: A cohort of n = 21 children
      living in Germany or Austria with monogenic obesity due to congenital leptin
      deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and
      primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed.
      A control group (CTRL) was defined that consisted of n = 22 obese adolescents
      with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI
      trajectories were compared between the groups at selected time points. RESULTS:
      The LEP and LEPR group showed a tremendous increase in BMI during the first 2
      years of life with all patients displaying a BMI >27 kg/m2 (27.2-38.4 kg/m2) and
      %BMIP95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8
      198.6%) at the age of 2 years and a BMI > 33 kg/m2 (33.3-45.9 kg/m2) and %BMIP95
      > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later
      onset of obesity with significantly lower BMI values at both time points (p <
      0.01). CONCLUSION: As result of the investigation of early childhood BMI
      trajectories in this pediatric cohort with monogenic obesity we suggest that BMI
      values >27.0 kg/m2 or %BMIP95 > 140% at the age of 2 years and BMI values >33.0
      kg/m2 or %BMIP95 > 184% at the age of 5 years may be useful cut points to
      identify children who should undergo genetic screening for monogenic obesity due
      to functionally relevant mutations in the leptin gene or leptin receptor gene.

PMID- 29568106
TI  - Socioeconomic differences in childhood BMI trajectories in Belarus.
AB  - OBJECTIVE: To examine associations of parental socioeconomic position with early
      life offspring body mass index (BMI) trajectories in a middle-income country.
      SUBJECTS: Overall, 12,385 Belarusian children born 1996-97 and enrolled in a
      randomised breastfeeding promotion trial at birth, with 3-14 measurements of BMI
      from birth to 7 years. METHODS: Cohort analysis in which exposures were parental
      education (common secondary or less; advanced secondary or partial university;
      completed university) and occupation (manual; non-manual) at birth, and the
      outcome was BMI z-score trajectories estimated using multilevel linear spline
      models, controlling for trial arm, location, parental BMI, maternal smoking
      status and number of older siblings. RESULTS: Infants born to university-educated
      mothers were heavier at birth than those born to secondary school-educated
      mothers [by 0.13 BMI z-score units (95% confidence interval, CI: 0.07, 0.19) for
      girls and 0.11 (95% CI: 0.05, 0.17) for boys; equivalent for an infant of average
      birth length to 43 and 38 g, respectively]. Between the ages of 3-7 years
      children of the most educated mothers had larger BMI increases than children of
      the least educated mothers. At age 7 years, after controlling for trial arm and
      location,  children of university-educated mothers had higher BMIs than those
      born to secondary school-educated mothers by 0.11 z-score (95% CI: 0.03, 0.19)
      among girls and 0.18 (95% CI: 0.1, 0.27) among boys, equivalent to differences in
      BMI for a child of average height of 0.19 and 0.26 kg/m2, respectively. After
      further controlling for parental BMI, these differences attenuated to 0.08 z
      score (95% CI: 0, 0.16) and 0.16 z-score (95% CI: 0.07, 0.24), respectively, but
      changed very little after additional adjustment for number of older siblings and
      mother's smoking status. Associations were similar when based on paternal
      educational attainment and highest household occupation. CONCLUSIONS: In Belarus,
      consistent with some middle-income countries, higher socioeconomic position was
      associated with greater BMI trajectories from age 3 onwards.

PMID- 29568107
TI  - Augmented capacity for peripheral serotonin release in human obesity.
AB  - BACKGROUND/OBJECTIVES: Evidence from animal studies highlights an important role
      for serotonin (5-HT), derived from gut enterochromaffin (EC) cells, in regulating
      hepatic glucose production, lipolysis and thermogenesis, and promoting obesity
      and dysglycemia. Evidence in humans is limited, although elevated plasma 5-HT
      concentrations are linked to obesity. SUBJECTS/METHODS: We assessed (i) plasma 5
      HT concentrations before and during intraduodenal glucose infusion (4 kcal/min
      for 30 min) in non-diabetic obese (BMI 44 +/- 4 kg/m2, N = 14) and control (BMI
      24 +/- 1 kg/m2, N = 10) subjects, (ii) functional activation of duodenal EC cells
      (immunodetection of phospho-extracellular related-kinase, pERK) in response to
      glucose, and in separate subjects, (iii) expression of tryptophan hydroxylase-1
      (TPH1) in duodenum and colon (N = 39), and (iv) 5-HT content in primary EC cells
      from these regions (N = 85). RESULTS: Plasma 5-HT was twofold higher in obese
      than control responders prior to (P = 0.025), and during (iAUC, P = 0.009),
      intraduodenal glucose infusion, and related positively to BMI (R2 = 0.334, P =
      0.003) and HbA1c (R2 = 0.508, P = 0.009). The density of EC cells in the duodenum
      was twofold higher at baseline in obese subjects than controls (P = 0.023), with
      twofold more EC cells activated by glucose infusion in the obese (EC cells co
      expressing 5-HT and pERK, P = 0.001), while the 5-HT content of EC cells in
      duodenum and colon was similar; TPH1 expression was 1.4-fold higher in the
      duodenum of obese subjects (P = 0.044), and related positively to BMI (R2 =
      0.310, P = 0.031). CONCLUSIONS: Human obesity is characterized by an increased
      capacity to produce and release 5-HT from the proximal small intestine, which is
      strongly linked to higher body mass, and glycemic control. Gut-derived 5-HT is
      likely to be an important driver of pathogenesis in human obesity and
      dysglycemia.

PMID- 29568108
TI  - Lifestyle of women before pregnancy and the risk of offspring obesity during
      childhood through early adulthood.
AB  - BACKGROUND: In women, adhering to an overall healthy lifestyle is associated with
      a dramatically reduced risk of cardio-metabolic disorders. Whether such a healthy
      lifestyle exerts an intergenerational effects on child health deserves
      examination. METHODS: We included 5701 children (9-14 years old at baseline) of
      the Growing Up Today Study 2, and their mothers, who are participants in the
      Nurses' Health Study II. Pre-pregnancy healthy lifestyle was defined as a normal
      body mass index, no smoking, physical activity >=150 min/week, and diet in the
      top 40% of the Alternative Healthy Eating Index-2010. Obesity during childhood
      and adolescence was defined using the International Obesity Task Force age- and
      sex-specific cutoffs. Multivariable log-binominal regression models with
      generalized estimating equations were used to evaluate the association of pre
      pregnancy healthy lifestyle and offspring obesity. RESULTS: We identified 520
      (9.1%) offspring who became obese during follow-up. A healthy body weight of
      mothers and no smoking before pregnancy was significantly associated with a lower
      risk of obesity among offspring: the relative risks [RRs; 95% confidence
      intervals (CIs)] were 0.37 (0.31-0.43) and 0.64 (0.49-0.84), respectively. Eating
      a healthy diet and regular moderate-to-vigorous physical activities were
      inversely related to offspring obesity risk, but these relations were not
      statistically significant. Compared to children of mothers who did not meet any
      low-risk lifestyle factors, offspring of women who adhered to all four healthy
      lifestyle factors had 75% lower risk of obesity (RR: 0.25, 95% CI: 0.14-0.43).
      CONCLUSION: Adherence to an overall healthy lifestyle before pregnancy is
      strongly associated with a low risk of offspring obesity in childhood,
      adolescence, and early adulthood. These findings highlight the importance of an
      overall healthy lifestyle before pregnancy as a potential strategy to prevent
      obesity in future generations.

PMID- 29568110
TI  - Compositional associations of time spent in sleep, sedentary behavior and
      physical activity with obesity measures in children.
AB  - BACKGROUND/OBJECTIVES: The 24 h day is made up of four movement behaviors: sleep,
      sedentary behavior (SB), light intensity physical activity (LIPA), and moderate
      to-vigorous physical activity (MVPA). Previous studies examining associations
      between movement behaviors and obesity have used flawed statistical methods that
      did not account for the co-dependent and compositional nature of movement
      behaviors. Our objective was to use compositional data analysis methods to
      investigate the relationships between movement behaviors and obesity measures
      among children. SUBJECTS/METHODS: Participants were 434 children aged 10-13
      years. They wore an accelerometer for 7 days to determine time spent in SB, LIPA,
      and MVPA. Sleep duration was determined from the accelerometer and a log. The
      obesity measures were the body mass index, waist circumference, and fat mass
      index. Compositional data analysis was used to estimate whether the composition
      of movement behaviors was associated with obesity measures, and the extent to
      which changing time in movement behaviors within the movement behavior
      composition was associated with changes in obesity measures. RESULTS: The
      composition of movement behaviors across the 24 h day was associated with all
      three obesity measures (p < 0.001). Relative to other movement behaviors, time
      spent in MVPA was negatively associated with obesity measures (p < 0.01), time
      spent in LIPA was positively associated with obesity measures (p < 0.05), while
      time spent in SB and sleep were not associated with obesity measures. The
      estimates suggested that an 18 min/day increase in MVPA, 21 min/day decrease in
      LIPA, 87 min/day decrease in SB, or 67 min/day increase in sleep relative to the
      remaining behaviors would be associated with a 0.1 unit decrease in BMI z-score.
      CONCLUSIONS: The composition of movement behaviors across the day is associated
      with obesity measures. The findings suggest that changing the movement behavior
      composition by increasing MVPA and decreasing LIPA would be the most effective
      approach for improving obesity measures.

PMID- 29568109
TI  - Mitochondrial inefficiency in infants born to overweight African-American
      mothers.
AB  - BACKGROUND: Currently 20-35% of pregnant women are obese, posing a major health
      risk for mother and fetus. It is postulated that an abnormal maternal-fetal
      nutritional environment leads to adverse metabolic programming, resulting in
      altered substrate metabolism in the offspring and predisposing to risks of
      obesity and diabetes later in life. Data indicate that oocytes from overweight
      animals have abnormal mitochondria. We hypothesized that maternal obesity is
      associated with altered mitochondrial function in healthy neonatal offspring.
      METHODS: Overweight and obese (body mass index, (BMI) >= 25 kg/m2, n = 14) and
      lean (BMI < 25 kg/m2, n = 8), African-American pregnant women carrying male
      fetuses were recruited from the Barnes Jewish Hospital obstetric clinic. Maternal
      and infant data were extracted from medical records. Infants underwent body
      composition testing in the first days of life. Circumcision skin was collected
      for isolation of fibroblasts. Fibroblast cells were evaluated for mitochondrial
      function, metabolic gene expression, nutrient uptake, and oxidative stress.
      RESULTS: Skin fibroblasts of infants born to overweight mothers had significantly
      higher mitochondrial respiration without a concurrent increase in ATP production,
      indicating mitochondrial inefficiency. These fibroblasts had higher levels of
      reactive oxygen species and evidence of oxidative stress. Evaluation of gene
      expression in offspring fibroblasts revealed altered expression of multiple genes
      involved in fatty acid and glucose metabolism and mitochondrial respiration in
      infants of overweight mothers. CONCLUSIONS: This study demonstrates altered
      mitochondrial function and oxidative stress in skin fibroblasts of infants born
      to overweight mothers. Future studies are needed to determine the long-term
      impact of this finding on the metabolic health of these children.

PMID- 29568111
TI  - Obesity as a threat to national security: the need for precision engagement.

PMID- 29568112
TI  - Model formulation of microbial CO2 production and efficiency can significantly
      influence short and long term soil C projections.

PMID- 29568113
TI  - Multiple mechanisms drive phage infection efficiency in nearly identical hosts.
AB  - Phage-host interactions are critical to ecology, evolution, and biotechnology.
      Central to those is infection efficiency, which remains poorly understood,
      particularly in nature. Here we apply genome-wide transcriptomics and proteomics
      to investigate infection efficiency in nature's own experiment: two nearly
      identical (genetically and physiologically) Bacteroidetes bacterial strains
      (host18 and host38) that are genetically intractable, but environmentally
      important, where phage infection efficiency varies. On host18, specialist phage
      phi18:3 infects efficiently, whereas generalist phi38:1 infects inefficiently. On
      host38, only phi38:1 infects, and efficiently. Overall, phi18:3 globally
      repressed host18's transcriptome and proteome, expressed genes that likely evaded
      host restriction/modification (R/M) defenses and controlled its metabolism, and
      synchronized phage transcription with translation. In contrast, phi38:1 failed to
      repress host18's transcriptome and proteome, did not evade host R/M defenses or
      express genes for metabolism control, did not synchronize transcripts with
      proteins and its protein abundances were likely targeted by host proteases.
      However, on host38, phi38:1 globally repressed host transcriptome and proteome,
      synchronized phage transcription with translation, and infected host38
      efficiently. Together these findings reveal multiple infection inefficiencies.
      While this contrasts the single mechanisms often revealed in laboratory mutant
      studies, it likely better reflects the phage-host interaction dynamics that occur
      in nature.

PMID- 29568115
TI  - The long and latent road to autoimmunity.

PMID- 29568114
TI  - Population genomic analysis of the rice blast fungus reveals specific events
      associated with expansion of three main clades.
AB  - We examined the genomes of 100 isolates of Magnaporthe oryzae (Pyricularia
      oryzae), the causal agent of rice blast disease. We grouped current field
      populations of M. oryzae into three major globally distributed groups. A
      genetically diverse group, clade 1, which may represent a group of closely
      related lineages, contains isolates of both mating types. Two well-separated
      clades, clades 2 and 3, appear to have arisen as clonal lineages distinct from
      the genetically diverse clade. Examination of genes involved in mating pathways
      identified clade-specific diversification of several genes with orthologs
      involved in mating behavior in other fungi. All isolates within each clonal
      lineage are of the same mating type. Clade 2 is distinguished by a unique
      deletion allele of a gene encoding a small cysteine-rich protein that we
      determined to be a virulence factor. Clade 3 isolates have a small deletion
      within the MFA2 pheromone precursor gene, and this allele is shared with an
      unusual group of isolates we placed within clade 1 that contain AVR1-CO39
      alleles. These markers could be used for rapid screening of isolates and suggest
      specific events in evolution that shaped these populations. Our findings are
      consistent with the view that M. oryzae populations in Asia generate diversity
      through recombination and may have served as the source of the clades 2 and 3
      isolates that comprise a large fraction of the global population.

PMID- 29568116
TI  - Induction of human dendritic cell maturation by naive and memory B-cell subsets
      requires different activation stimuli.

PMID- 29568117
TI  - Distinct contribution of PD-L1 suppression by spatial expression of PD-L1 on
      tumor and non-tumor cells.
AB  - Programmed cell death receptor 1 (PD-1) and its ligand, PD-L1, are important
      immune checkpoint proteins. Although antibodies that block PD-1/PD-L1 have shown
      promising clinical efficacy in a subset of cancer patients, the detailed cellular
      and molecular mechanisms behind anti-PD-1 and anti-PD-L1 immunotherapy are not
      well defined. Specifically, the way in which PD-L1 contributes to immune
      suppression on tumor and non-tumor cells remains controversial. By selectively
      blocking PD-L1 on either tumor or non-tumor cells, we demonstrated that PD-L1
      from both sources suppressed the anti-tumor T-cell response. Blocking PD-L1 on
      either tumor cells or non-tumor cells inhibited tumor growth and enhanced immune
      cell infiltration, as well as the tumor-specific T-cell response. Further,
      simultaneously blocking tumor- and non-tumor-derived PD-L1 maximized anti-tumor T
      cell responses and demonstrated synergy. In addition, the relative contribution
      of PD-L1 on tumor and non-tumor cells to immune suppression depended on the PD-L1
      expression level. Lastly, we found that the F4/80 receptor was involved in the
      anti-tumor effect of PD-L1 blockade. Taken together, our data indicate that PD-L1
      on both tumor and non-tumor cells is critical for T-cell inhibition, which
      provides new directions for the optimization of PD-L1-blocking antibodies and the
      development of clinical biomarker strategies.

PMID- 29568119
TI  - TREM-1 multimerization is essential for its activation on monocytes and
      neutrophils.
AB  - The triggering receptor expressed on myeloid cells-1 (TREM-1) is a receptor
      expressed on innate immune cells. By promoting the amplification of inflammatory
      signals that are initially triggered by Toll-like receptors (TLRs), TREM-1 has
      been characterized as a major player in the pathophysiology of acute and chronic
      inflammatory diseases, such as septic shock, myocardial infarction,
      atherosclerosis, and inflammatory bowel diseases. However, the molecular events
      leading to the activation of TREM-1 in innate immune cells remain unknown. Here,
      we show that TREM-1 is activated by multimerization and that the levels of
      intracellular Ca2+ release, reactive oxygen species, and cytokine production
      correlate with the degree of TREM-1 aggregation. TREM-1 activation on primary
      human monocytes by LPS required a two-step process consisting of upregulation
      followed by clustering of TREM-1 at the cell surface, in contrast to primary
      human neutrophils, where LPS induced a rapid cell membrane reorganization of TREM
      1, which confirmed that TREM-1 is regulated differently in primary human
      neutrophils and monocytes. In addition, we show that the ectodomain of TREM-1 is
      able to homooligomerize in a concentration-dependent manner, which suggests that
      the clustering of TREM-1 on the membrane promotes its oligomerization. We further
      show that the adapter protein DAP12 stabilizes TREM-1 surface expression and
      multimerization. TREM-1 multimerization at the cell surface is also mediated by
      its endogenous ligand, a conclusion supported by the ability of the TREM-1
      inhibitor LR12 to limit TREM-1 multimerization. These results provide evidence
      for ligand-induced, receptor-mediated dimerization of TREM-1. Collectively, our
      findings uncover the mechanisms necessary for TREM-1 activation in monocytes and
      neutrophils.

PMID- 29568118
TI  - The cellular metabolic landscape in the tumor milieu regulates the activity of
      myeloid infiltrates.
AB  - Malignant cells upregulate distinct energy metabolism programs that support their
      proliferation, migration, and adaptation to the stressful tumor microenvironment
      (TME). Additionally, this exaggerated metabolic activity allows cancer cells to
      hijack essential nutrients and outcompete neighboring infiltrating immune cells,
      thereby impairing antitumor immunity. During recent years, there has been great
      interest in the field to understand the tumor-induced energy metabolism signals
      that regulate the function of immune cells in individuals with cancer.
      Accordingly, it is now well accepted that uncovering the mechanisms that instruct
      the metabolic behavior of cancer cells and tumor-associated immune cells is an
      indispensable strategy for the development of new approaches to overcome immune
      suppression in tumors. Thus, in this minireview, we briefly discuss the
      interaction between particular metabolic signaling pathways and immunosuppressive
      activity in different subsets of myeloid cells within the TME. Additionally, we
      illustrate potential central mechanisms controlling the metabolic reprogramming
      of myeloid cells in response to tumor-derived factors.

PMID- 29568120
TI  - Role of Hippo signaling in regulating immunity.
AB  - The Hippo signaling pathway has been established as a key regulator of organ size
      control, tumor suppression, and tissue regeneration in multiple organisms.
      Recently, emerging evidence has indicated that Hippo signaling might play an
      important role in regulating the immune system in both Drosophila and mammals. In
      particular, patients bearing a loss-of-function mutation of MST1 are reported to
      have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases,
      the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo
      signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential
      signaling pathways to regulate both innate and adaptive immunity. In this review,
      we present and discuss recent findings of cellular mechanisms/functions of Hippo
      signaling in the innate immunity in Drosophila and in mammals, T cell immunity,
      as well as the implications of Hippo signaling for tumor immunity.

PMID- 29568121
TI  - The role of transcriptional factor D-site-binding protein in circadian CCL2 gene
      expression in anti-Thy1 nephritis.
AB  - Mesangial proliferative glomerulonephritis (MsPGN) is an inflammatory disease,
      but both the nature of disease progression and its regulation remain unclear. In
      the present study, we monitored the course of anti-Thy1 nephritis from days 1 to
      5 and established gene expression profiles at each time point using microarrays
      to explore the development of inflammation. According to the gene expression
      profiles, macrophage infiltration (triggered by CCL2 activation) was evident on
      day 1 and enhanced inflammation over the next few days. We screened for genes
      with expression levels similar to CCL2 and found that the upregulation of the
      circadian gene albumin D-site-binding protein (DBP) was involved in CCL2
      activation in mesangial cells. More importantly, CCL2 expression showed
      oscillatory changes similar to DBP, and DBP induced peak CCL2 expression at 16:00
      a clock on day 1 in the anti-Thy1 nephritis model. We knocked down DBP through
      transfection with a small interfering RNA (siRNA) and used RNA sequencing to
      identify the DBP-regulated TNF-alpha-CCL2 pathway. We performed chromatin
      immunoprecipitation sequencing (ChIP-Seq) and the dual luciferase assay to show
      that DBP bound to the TRIM55 promoter, regulating gene expression and in turn
      controlling the TNF-alpha-CCL2 pathway. In conclusion, DBP-regulated circadian
      CCL2 expression by the TRIM55-TNF pathway in injured mesangial cells at an early
      stage, which promoted macrophage recruitment and in turn triggered infiltration
      and inflammation in a model of anti-Thy1 nephritis.

PMID- 29568122
TI  - Evaluation of selected insomnia predictors in adolescents and young adults with
      cystic fibrosis.
AB  - AIMS AND BACKGROUND: The purpose of the study was to assess the incidence of
      insomnia in adolescents and young adults with cystic fibrosis and its impact on
      the quality of life, and to examine whether demographic and clinical factors and
      negative emotional states are predictors of insomnia in these patients. METHODS:
      The study was conducted among 95 cystic fibrosis patients aged 14-25 years. The
      study used a personal questionnaire survey, the Athens Insomnia Scale, the Cystic
      Fibrosis Quality of Life Questionnaire, the Hospital Anxiety and Depression
      Scale, and the Numeric Rating Scale. RESULTS: Insomnia was diagnosed in 38% of
      cystic fibrosis patients. In patients with insomnia, the level of anxiety (Me: 10
      vs. 4; P=0.000) and depression (Me: 6.5 vs. 2; P=0.000) was significantly higher
      than in the good sleep quality group. The risk of insomnia increases as anxiety
      (OR: 4.31; 95% CI: 2.20 to 8.41) and depressive symptoms exacerbate (OR: 4.98;
      95% CI: 1.84 to 13.43). Insomnia significantly worsens the quality of life in
      cystic fibrosis patients (beta=-0.5, P=0.000). CONCLUSION: Insomnia affects a
      large percentage of cystic fibrosis patients, and anxiety and depression are
      factors that increase the risk of insomnia. Insomnia decreases the quality of
      life in cystic fibrosis patients.

PMID- 29568123
TI  - Non-instrumental clinical monitoring does not guarantee an adequate course of
      general anesthesia. A prospective clinical study.
AB  - BACKGROUND: Clinical monitoring is the most common method of adjusting the
      appropriate level of general anesthesia. However, episodes of intraoperative
      awareness (AWR) are still reported, suggesting that clinical observations may not
      be sufficient in some cases. The objective of this study was to compare the
      efficacy of clinical and instrumental neuromonitoring with auditory evoked
      potentials (AEP) in an intraoperative analysis of the proper level of general
      anesthesia. METHODS: Patients scheduled for elective surgery were randomly
      divided into two groups. Subjects in the first group underwent intravenous, in
      the second group volatile anesthesia. The adequacy of anesthesia was analyzed
      using clinical parameters. All the participants were instrumentally monitored
      with the autoregressive AEP index (AAI). After the anesthesia, patients filled
      out a questionnaire on possible AWR. RESULTS: Data of 208 patients (87 in the
      first, and 121 in the second group) were analyzed. Before surgery there were no
      changes in AAI values between groups (80 vs. 78, P=0.5192). The mean values of
      clinical parameters changed, but five minutes after the nociceptive stimuli. The
      mean values of AAI at analyzed time points were specific for general anesthesia.
      In patients under intravenous anesthesia, we found more episodes of too low
      (46/608 vs.15/847, P<0.000) anesthesia. One case of AWR was found in the TIVA
      group. CONCLUSIONS: AAI index is good indicator of patients' level of
      consciousness during general anesthesia. Standard clinical monitoring provides
      appropriate level of the procedure. However, it is insufficient during TIVA and
      does not prevent episodes of AWR.

PMID- 29568124
TI  - How Does Household Income Affect Child Personality Traits and Behaviors?
AB  - We examine the effects of a quasi-experimental unconditional household income
      transfer on child emotional and behavioral health and personality traits. Using
      longitudinal data, we find that there are large beneficial effects on children's
      emotional and behavioral health and personality traits during adolescence. We
      find evidence that these effects are most pronounced for children who start out
      with the lowest initial endowments. The income intervention also results in
      improvements in parental relationships which we interpret as a potential
      mechanism behind our findings.

PMID- 29568126
TI  - Reimagining GIScience for relational spaces.
AB  - A mismatch between largely absolute Newtonian models of space in GIScience and
      the relational spaces of critical human geography has contributed to mutual
      disinterest between the fields. Critical GIS has offered an intellectual critique
      of GIScience without substantially altering how particular key geographical
      concepts are expressed in data structures. Although keystone ideas in GIScience
      such as Tobler's "First Law" and the modifiable areal unit problem speak to
      enduring concerns of human geography, they have drawn little interest from that
      field. Here, we suggest one way to reformulate the computational approach to the
      region for relational space, so that regions emerge not through proximity in an
      absolute space or similarities in intensive properties, but according to their
      similarities in relations. We show how this might operate theoretically and
      empirically, working through three illustrative examples. Our approach gestures
      toward reformulating key terms in GIScience like distance, proximity, networks,
      and spatial building blocks such as the polygon. Re-engaging the challenges of
      representing geographical concepts computationally can yield new kinds of GIS and
      GIScience resonant with theoretical ideas in human geography, and also lead to
      critical human geographic practices less antagonistic to computation.

PMID- 29568125
TI  - THE EARTH SYSTEM PREDICTION SUITE: Toward a Coordinated U.S. Modeling Capability.
AB  - The Earth System Prediction Suite (ESPS) is a collection of flagship U.S. weather
      and climate models and model components that are being instrumented to conform to
      interoperability conventions, documented to follow metadata standards, and made
      available either under open source terms or to credentialed users. The ESPS
      represents a culmination of efforts to create a common Earth system model
      architecture, and the advent of increasingly coordinated model development
      activities in the U.S. ESPS component interfaces are based on the Earth System
      Modeling Framework (ESMF), community-developed software for building and coupling
      models, and the National Unified Operational Prediction Capability (NUOPC) Layer,
      a set of ESMF-based component templates and interoperability conventions. This
      shared infrastructure simplifies the process of model coupling by guaranteeing
      that components conform to a set of technical and semantic behaviors. The ESPS
      encourages distributed, multi-agency development of coupled modeling systems,
      controlled experimentation and testing, and exploration of novel model
      configurations, such as those motivated by research involving managed and
      interactive ensembles. ESPS codes include the Navy Global Environmental Model
      (NavGEM), HYbrid Coordinate Ocean Model (HYCOM), and Coupled Ocean Atmosphere
      Mesoscale Prediction System (COAMPS(r)); the NOAA Environmental Modeling System
      (NEMS) and the Modular Ocean Model (MOM); the Community Earth System Model
      (CESM); and the NASA ModelE climate model and GEOS-5 atmospheric general
      circulation model.

PMID- 29568127
TI  - Experimental investigation of reinforced bonded joints for composite laminates.
AB  - An experimental study has been carried out to investigate the behaviour of co
      bonded carbon fibre reinforced plastics joints with a novel design incorporating
      a through the thickness local reinforcement. Different specimens were
      manufactured to investigate static and fatigue behaviour, as well as delamination
      size after impact and damage tolerance characteristics. The mechanical
      performances of the specimens with local reinforcement, consisting of the
      insertion of spiked thin metal sheets between co-bonded laminates, were compared
      with those ones obtained from specimens with purely co-bonded joints. This novel
      design demonstrated by tests that damage progression under cycling load results
      significantly delayed by the reinforcements. A significant number of experimental
      results were obtained that can be used to define preliminary design guidelines.

PMID- 29568128
TI  - The role of Bezier extraction in adaptive isogeometric analysis: Local refinement
      and hierarchical refinement.
AB  - We present 2 adaptive refinement techniques, namely, adaptive local refinement
      and adaptive hierarchical refinement, for isogeometric analysis. An element-wise
      point of view is adopted, exploiting Bezier extraction, which facilitates the
      implementation of adaptive refinement in isogeometric analysis. Locally refined
      and hierarchical T-splines are used for the description of the geometry as well
      as for the approximation of the solution space in the analysis. The refinement is
      conducted with the aid of a subdivision operator, which is computed by again
      exploiting the Bezier extraction operator. The concept and algorithm of an
      element-based adaptive isogeometric analysis are illustrated. Numerical examples
      are given to examine the accuracy, the convergence, and the condition number.

PMID- 29568129
TI  - A Review of Lewis R. Rambo and Charles E. Farhadian's The Oxford Handbook of
      Religious Conversion.
AB  - This is a review of the Oxford Handbook of Religious Conversion. Drawing upon
      research on Germans converting to Islam and Turks converting to Christianity,
      converting is understood as complex fusion of individual choice and
      cultural/political conflict.

PMID- 29568130
TI  - An evaluation of the performance and suitability of R * C methods for ecological
      inference with known true values.
AB  - Ecological inference refers to the study of individuals using aggregate data and
      it is used in an impressive number of studies; it is well known, however, that
      the study of individuals using group data suffers from an ecological fallacy
      problem (Robinson in Am Sociol Rev 15:351-357, 1950). This paper evaluates the
      accuracy of two recent methods, the Rosen et al. (Stat Neerl 55:134-156, 2001)
      and the Greiner and Quinn (J R Stat Soc Ser A (Statistics in Society) 172:67-81,
      2009) and the long-standing Goodman's (Am Sociol Rev 18:663-664, 1953; Am J
      Sociol 64:610-625, 1959) method designed to estimate all cells of R * C tables
      simultaneously by employing exclusively aggregate data. To conduct these tests we
      leverage on extensive electoral data for which the true quantities of interest
      are known. In particular, we focus on examining the extent to which the
      confidence intervals provided by the three methods contain the true values. The
      paper also provides important guidelines regarding the appropriate contexts for
      employing these models.

PMID- 29568131
TI  - Causal conditions for loneliness: a set-theoretic analysis on an adult sample in
      the UK.
AB  - While age has been identified as a risk factor for loneliness, whether it is a
      necessary or sufficient condition for loneliness has never been examined. This is
      the first study that applies fuzzy-set QCA, a special type of set-theoretic
      method, to discover the necessary and sufficient causal conditions for
      loneliness, respectively, among adults in the UK, analysing the data collected
      from the UK sample of Round 6 of the European Social Survey (ESS, 2012, n =
      2163). It firstly examines the configurations of five conditions: being female,
      old age, not living with spouse/partner, bad health, and not being frequently
      social with others. Gender was found neither a necessary nor a sufficient
      condition for loneliness, and old age was close to being a necessary condition
      and became necessary when united with any of the other conditions; the
      configuration of not living with spouse/partner and not healthy and not
      frequently social with others is a sufficient condition. Robustness of results
      was tested with two different conditions (a limiting illness and a confidante),
      and a separate analysis on the absence of loneliness was conducted. The effect of
      the unbalanced distribution of cases across different values of the outcome was
      highlighted as a source of uncertainty, and the results on the absence of
      loneliness are different from those on its presence.

PMID- 29568132
TI  - The hierarchical age-period-cohort model: Why does it find the results that it
      finds?
AB  - It is claimed the hierarchical-age-period-cohort (HAPC) model solves the age
      period-cohort (APC) identification problem. However, this is debateable;
      simulations show situations where the model produces incorrect results, countered
      by proponents of the model arguing those simulations are not relevant to real
      life scenarios. This paper moves beyond questioning whether the HAPC model works,
      to why it produces the results it does. We argue HAPC estimates are the result
      not of the distinctive substantive APC processes occurring in the dataset, but
      are primarily an artefact of the data structure-that is, the way the data has
      been collected. Were the data collected differently, the results produced would
      be different. This is illustrated both with simulations and real data, the latter
      by taking a variety of samples from the National Health Interview Survey (NHIS)
      data used by Reither et al. (Soc Sci Med 69(10):1439-1448, 2009) in their HAPC
      study of obesity. When a sample based on a small range of cohorts is taken, such
      that the period range is much greater than the cohort range, the results produced
      are very different to those produced when cohort groups span a much wider range
      than periods, as is structurally the case with repeated cross-sectional data. The
      paper also addresses the latest defence of the HAPC model by its proponents
      (Reither et al. in Soc Sci Med 145:125-128, 2015a). The results lend further
      support to the view that the HAPC model is not able to accurately discern APC
      effects, and should be used with caution when there appear to be period or cohort
      near-linear trends.

PMID- 29568133
TI  - The adequacy of measures of gender roles attitudes: a review of current measures
      in omnibus surveys.
AB  - The measures of attitudes toward gender roles included in many representative
      international and national omnibus surveys were developed mostly in the 1970s and
      1980s with a focus on the male breadwinner model. This article deals with the
      issue of whether the measures provided in these omnibus surveys need to be
      adjusted to specific social changes. A review of these measures has found that
      adjustments have occurred in a limited way that focused on the role of women and
      disregarded the role of men. Furthermore, most of these measures only examined
      the traditional roles of men and women. More egalitarian role models have not
      been considered sufficiently. In addition, most items that have been measured are
      phrased in a general form and, for example, do not specify parents' employment or
      the ages of children. A specification of these aspects of measurement would help
      to clarify the conceptual meaning of the results and increase the possibility of
      more accurately analyzing gender role attitudes over time.

PMID- 29568134
TI  - Environmental recidivism in Sweden: distributional shape and effects of sanctions
      on duration of compliance.
AB  - The study examines the association between the size of previous environmental
      sanction charges and subsequent compliance towards environmental regulations.
      Data used for the study come from about 9000 Swedish firms fined sometime between
      January 2002 and December 2012. Probabilities of compliance across various levels
      of sanctions are estimated using life-table methods and tested for equality using
      standard nonparametric methods. Association between size of sanction charges and
      subsequent behaviour is modelled by proportional hazard model for the rate of
      recidivism as well as by a family of flexible parametric accelerated failure-time
      models for the duration of compliance. The results show that duration of
      compliance may be described by a log-normal distribution. Further, it is
      demonstrated that sanctions charges do have significant detering effects on the
      risk of recidivism though the strength of the detering effect depends on whether
      or not we account for other possible correlates of recidivism. Possible
      explanations of the results and their policy implications are discussed;
      limitations of the current study highlighted; and potential extensions for future
      studies outlined.

PMID- 29568135
TI  - Distributed dynamic simulations of networked control and building performance
      applications.
AB  - The use of computer-based automation and control systems for smart sustainable
      buildings, often so-called Automated Buildings (ABs), has become an effective way
      to automatically control, optimize, and supervise a wide range of building
      performance applications over a network while achieving the minimum energy
      consumption possible, and in doing so generally refers to Building Automation and
      Control Systems (BACS) architecture. Instead of costly and time-consuming
      experiments, this paper focuses on using distributed dynamic simulations to
      analyze the real-time performance of network-based building control systems in
      ABs and improve the functions of the BACS technology. The paper also presents the
      development and design of a distributed dynamic simulation environment with the
      capability of representing the BACS architecture in simulation by run-time
      coupling two or more different software tools over a network. The application and
      capability of this new dynamic simulation environment are demonstrated by an
      experimental design in this paper.

PMID- 29568136
TI  - GENDER IN LOW- AND MIDDLE-INCOME COUNTRIES: GENERAL METHODS.

PMID- 29568137
TI  - GIRLS' AND BOYS' LABOR AND HOUSEHOLD CHORES IN LOW- AND MIDDLE-INCOME COUNTRIES.

PMID- 29568138
TI  - GENDER IN LOW- AND MIDDLE-INCOME COUNTRIES: REFLECTIONS, LIMITATIONS, DIRECTIONS,
      AND IMPLICATIONS.

PMID- 29568139
TI  - Correlation of ICME Magnetic Fields at Radially Aligned Spacecraft.
AB  - The magnetic field structures of two interplanetary coronal mass ejections
      (ICMEs), each observed by a pair of spacecraft close to radial alignment, have
      been analysed. The ICMEs were observed in situ by MESSENGER and STEREO-B in
      November 2010 and November 2011, while the spacecraft were separated by more than
      0.6 AU in heliocentric distance, less than 4 degrees  in heliographic longitude,
      and less than 7 degrees  in heliographic latitude. Both ICMEs took approximately
      two days to travel between the spacecraft. The ICME magnetic field profiles
      observed at MESSENGER have been mapped to the heliocentric distance of STEREO-B
      and compared directly to the profiles observed by STEREO-B. Figures that result
      from this mapping allow for easy qualitative assessment of similarity in the
      profiles. Macroscale features in the profiles that varied on timescales of one
      hour, and which corresponded to the underlying flux rope structure of the ICMEs,
      were well correlated in the solar east-west and north-south directed components,
      with Pearson's correlation coefficients of approximately 0.85 and 0.95,
      respectively; microscale features with timescales of one minute were
      uncorrelated. Overall correlation values in the profiles of one ICME were
      increased when an apparent change in the flux rope axis direction between the
      observing spacecraft was taken into account. The high degree of similarity seen
      in the magnetic field profiles may be interpreted in two ways. If the spacecraft
      sampled the same region of each ICME (i.e. if the spacecraft angular separations
      are neglected), the similarity indicates that there was little evolution in the
      underlying structure of the sampled region during propagation. Alternatively, if
      the spacecraft observed different, nearby regions within the ICMEs, it indicates
      that there was spatial homogeneity across those different regions. The field
      structure similarity observed in these ICMEs points to the value of placing in
      situ space weather monitors well upstream of the Earth.

PMID- 29568140
TI  - A general protocol for radical anion [3 + 2] cycloaddition enabled by tandem
      Lewis acid photoredox catalysis.
AB  - We report herein a method for intermolecular [3 + 2] cycloaddition between aryl
      cyclopropyl ketones and alkenes involving the combination of Lewis acid and
      photoredox catalysis. In contrast to other more common methods for [3 + 2]
      cycloaddition, these conditions operate using a broad range of both electron-rich
      and electron-deficient reaction partners. The critical factors predicting the
      success of these reactions is the redox potential of the cyclopropyl ketone and
      the ability of the alkene to stabilize a key radical intermediate.

PMID- 29568141
TI  - Distinguishing remobilized ash from erupted volcanic plumes using space-borne
      multi-angle imaging.
AB  - Volcanic systems are comprised of a complex combination of ongoing eruptive
      activity and secondary hazards, such as remobilized ash plumes. Similarities in
      the visual characteristics of remobilized and erupted plumes, as imaged by
      satellite-based remote sensing, complicate the accurate classification of these
      events. The stereo imaging capabilities of the Multi-angle Imaging
      SpectroRadiometer (MISR) were used to determine the altitude and distribution of
      suspended particles. Remobilized ash shows distinct dispersion, with particles
      distributed within ~1.5 km of the surface. Particle transport is consistently
      constrained by local topography, limiting dispersion pathways downwind. The MISR
      Research Aerosol (RA) retrieval algorithm was used to assess plume particle
      microphysical properties. Remobilized ash plumes displayed a dominance of large
      particles with consistent absorption and angularity properties, distinct from
      emitted plumes. The combination of vertical distribution, topographic control,
      and particle microphysical properties makes it possible to distinguish
      remobilized ash flows from eruptive plumes, globally.

PMID- 29568142
TI  - Differences in Sexual Behavior of Teenagers and Young Adults with Cerebral Palsy:
      The Role of Sexual Needs and Sexual Esteem.
AB  - Sexuality is an inherent attribute of all human beings regardless of their race,
      religion and the level of physical fitness. The way it is perceived and
      manifested is determined by a number of biopsychosocial factors. In some people,
      including persons with cerebral palsy, the factors and their influence are rooted
      in the psychophysical condition of the human body. The aim of this study was to
      answer the question about how the levels of sexual esteem and sexual needs
      differentiate the sexual behaviors of young people with cerebral palsy. The study
      being presented was conducted with 62 young persons with cerebral palsy (half
      women and half men), who were selected using purposive sampling. They were aged
      15-25 years and were individuals without cognitive difficulties. The research
      tool used was the Cerebral Palsy Individual's Sexual Behavior Questionnaire
      developed by the authors. The findings of the study showed that half of the
      participants engaged in various sexual behaviors from the list that was presented
      to them. The frequencies of these engagements depended on the levels of their
      sexual esteem and sexual needs. Persons characterized by high levels of sexual
      esteem and sexual needs (much fewer than those with the low levels of both
      characteristics) engaged in sexual behaviors significantly more frequently. The
      most frequent among them was direct engagement in sexual activity (petting and
      sexual intercourse; p <= .001) and then exposure to sexually explicit magazines
      or films (p <= .05).

PMID- 29568143
TI  - Populism and Feminism: Odd Bedfellows.
AB  - In this era of populist insurgency breaking the mold of democratic politics, two
      movements clashed.They represented opposite sides of the political spectrum, one
      emancipatory, the other exclusionary. One may be identified as feminism, the
      other as populism. This essay analyzes both concepts and explores their
      connection.

PMID- 29568144
TI  - Youth Disclosure of Sexual Orientation to Siblings and Extended Family.
AB  - Objective: To explore the processes and experiences associated with disclosing
      sexual orientation to siblings and extended family. Background: Few studies
      prioritize the experience of disclosing to siblings and extended family, despite
      its frequency and potential impact on the family unit. Extended family members
      often act as sources of support for youth; it is therefore worthwhile to consider
      whether this remains true during and after disclosure of sexual orientation.
      Method: Interview and questionnaire data were gathered from 22 lesbian, gay,
      bisexual, and queer (LGBQ) youth, 14 to 21 years of age, from a large Midwestern
      city. Constructivist grounded theory informed the qualitative methodology and
      data analysis. We build on concepts of horizontal and vertical family
      relationships by also introducing the concept of diagonal relationships. Results:
      Participants described their relationships with aunts as possessing
      characteristics of horizontal and vertical relationships, allowing them to act as
      moderators and mediators of the parent-child relationship. Conclusion: The
      concepts of vertical, horizontal, and diagonal relationships take into
      consideration how the structure (e.g., hierarchy, egalitarianism, boundaries) and
      nature (e.g., closeness, reciprocity, mentorship) of various relationships shape
      the coming-out process for LGBQ youth, without dismissing the importance of
      either immediate or extended family members. Implications: The emerging
      conceptualization can guide services and interventions as well as illuminate
      further research on the family systems of LGBQ youth.

PMID- 29568145
TI  - The impact of parenthood on environmental attitudes and behaviour: a longitudinal
      investigation of the legacy hypothesis.
AB  - Willingness to engage in sustainable actions may be limited by the psychological
      distance of climate change. In this study, we test the legacy hypothesis, which
      holds that having children leads parents to consider the legacy left to offspring
      in respect of environmental quality. Using the Understanding Society dataset, a
      longitudinal survey representative of the UK population (n = 18,176), we assess
      how having children may change people's individual environmental attitudes and
      behaviour. Results indicate that having a new child is associated with a small
      decrease in the frequency of a few environmental behaviours. Only parents with
      already high environmental concern show a small increase in the desire to act
      more sustainably after the birth of their first child. Overall, the results do
      not provide evidence in support of the legacy hypothesis in terms of individual
      level environmental attitudes and behaviours. We argue that the transition to
      parenthood is a time where concern is prioritised on the immediate wellbeing of
      the child and not on the future environmental threats.

PMID- 29568146
TI  - Voxel-based plaque classification in coronary intravascular optical coherence
      tomography images using decision trees.
AB  - Intravascular Optical Coherence Tomography (IVOCT) is a high contrast, 3D
      microscopic imaging technique that can be used to assess atherosclerosis and
      guide stent interventions. Despite its advantages, IVOCT image interpretation is
      challenging and time consuming with over 500 image frames generated in a single
      pullback volume. We have developed a method to classify voxel plaque types in
      IVOCT images using machine learning. To train and test the classifier, we have
      used our unique database of labeled cadaver vessel IVOCT images accurately
      registered to gold standard cryo-images. This database currently contains 300
      images and is growing. Each voxel is labeled as fibrotic, lipid-rich, calcified
      or other. Optical attenuation, intensity and texture features were extracted for
      each voxel and were used to build a decision tree classifier for multi-class
      classification. Five-fold cross-validation across images gave accuracies of 96 %
      +/- 0.01 %, 90 +/- 0.02% and 90 % +/- 0.01 % for fibrotic, lipid-rich and
      calcified classes respectively. To rectify performance degradation seen in left
      out vessel specimens as opposed to left out images, we are adding data and
      reducing features to limit overfitting. Following spatial noise cleaning,
      important vascular regions were unambiguous in display. We developed displays
      that enable physicians to make rapid determination of calcified and lipid
      regions. This will inform treatment decisions such as the need for devices (e.g.,
      atherectomy or scoring balloon in the case of calcifications) or extended stent
      lengths to ensure coverage of lipid regions prone to injury at the edge of a
      stent.

PMID- 29568147
TI  - Comparison of quantitative myocardial perfusion imaging CT to fluorescent
      microsphere-based flow from high-resolution cryo-images.
AB  - Myocardial perfusion imaging using CT (MPI-CT) has the potential to provide
      quantitative measures of myocardial blood flow (MBF) which can aid the diagnosis
      of coronary artery disease. We evaluated the quantitative accuracy of MPI-CT in a
      porcine model of balloon-induced LAD coronary artery ischemia guided by
      fractional flow reserve (FFR). We quantified MBF at baseline (FFR=1.0) and under
      moderate ischemia (FFR=0.7) using MPI-CT and compared to fluorescent microsphere
      based MBF from high-resolution cryo-images. Dynamic, contrast-enhanced CT images
      were obtained using a spectral detector CT (Philips Healthcare). Projection-based
      mono-energetic images were reconstructed and processed to obtain MBF. Three MBF
      quantification approaches were evaluated: singular value decomposition (SVD) with
      fixed Tikhonov regularization (ThSVD), SVD with regularization determined by the
      L-Curve criterion (LSVD), and Johnson-Wilson parameter estimation (JW). The three
      approaches over-estimated MBF compared to cryo-images. JW produced the most
      accurate MBF, with average error 33.3+/-19.2mL/min/100g, whereas LSVD and ThSVD
      had greater over-estimation, 59.5+/-28.3mL/min/100g and 78.3+/-25.6 mL/min/100g,
      respectively. Relative blood flow as assessed by a flow ratio of LAD-to-remote
      myocardium was strongly correlated between JW and cryo-imaging, with R2=0.97,
      compared to R2=0.88 and 0.78 for LSVD and ThSVD, respectively. We assessed tissue
      impulse response functions (IRFs) from each approach for sources of error. While
      JW was constrained to physiologic solutions, both LSVD and ThSVD produced IRFs
      with non-physiologic properties due to noise. The L-curve provided noise-adaptive
      regularization but did not eliminate non-physiologic IRF properties or optimize
      for MBF accuracy. These findings suggest that model-based MPI-CT approaches may
      be more appropriate for quantitative MBF estimation and that cryo-imaging can
      support the development of MPI-CT by providing spatial distributions of MBF.

PMID- 29568148
TI  - Children and Wild Foods in the Context of Deforestation in Rural Malawi.
AB  - There is growing recognition of the contribution of wild foods to local diets,
      nutrition, and culture. Yet disaggregation of understanding of wild food use by
      gender and age is limited. We used a mixed methods approach to determine the
      types, frequencies, and perceptions of wild foods used and sold by children in
      four villages in southern Malawi that have different levels of deforestation.
      Household and individual dietary diversity scores are low at all sites. All
      households consume one or more wild foods. Across the four sites, children listed
      119 wild foods, with a wider variety at the least deforested sites than the most
      deforested ones. Older children can name more wild foods than younger ones. More
      children from poor households sell wild foods than from well-off households.
      Several reasons were provided for the consumption or avoidance of wild foods
      (most commonly taste, contribution to health, limited alternatives, hunger,
      availability, local taboos).

PMID- 29568149
TI  - What makes Alpine swift ascend at twilight? Novel geolocators reveal year-round
      flight behaviour.
AB  - Abstract: Studying individual flight behaviour throughout the year is
      indispensable to understand the ecology of a bird species. Recent development in
      technology allows now to track flight behaviour of small long-distance bird
      migrants throughout its annual cycle. The specific flight behaviour of twilight
      ascents in birds has been documented in a few studies, but only during a short
      period of the year, and never quantified on the individual level. It has been
      suggested that twilight ascents might be a role in orientation and navigation.
      Previous studies had reported the behaviour only near the breeding site and
      during migration. We investigated year-round flight behaviour of 34 individual
      Alpine swifts (Apus melba) of four different populations in relation to twilight
      ascents. We recorded twilight ascents all around the year and found a twofold
      higher frequency in ascents during the non-breeding residence phase in Africa
      compared to all other phases of the year. Dawn ascents were twice as common as
      dusk ascents and occurred mainly when atmospheric conditions remained stable over
      a 24-h period. We found no conclusive support that twilight ascents are essential
      for recalibration of compass cues and landmarks. Data on the wing flapping
      intensity revealed that high activity at twilight occurred more regularly than
      the ascents. We therefore conclude that alpine swift generally increase flight
      activity-also horizontal flight-during the twilight period and we suppose that
      this increased flight activity, including ascents, might be part of social
      interactions between individuals. Significance statement: Year-round flight
      altitude tracking with a light-weight multi-sensor tag reveals that Alpine swifts
      ascend several hundred meters high at twilight regularly. The reason for this
      behaviour remains unclear and the low-light conditions at this time of the day
      preclude foraging as a possibility. The frequency and altitude of twilight
      ascents were highest during the non-breeding period, intermediate during
      migration and low for active breeders during the breeding phase. We discuss our
      findings in the context of existing hypotheses on twilight ascent and we propose
      an additional hypothesis which links twilight ascent with social interaction
      between flock members. Our study highlights how flight behaviour of individuals
      of a migratory bird species can be studied even during the sparsely documented
      non-breeding period.

PMID- 29568150
TI  - Limited social plasticity in the socially polymorphic sweat bee Lasioglossum
      calceatum.
AB  - Abstract: Eusociality is characterised by a reproductive division of labour,
      where some individuals forgo direct reproduction to instead help raise kin.
      Socially polymorphic sweat bees are ideal models for addressing the mechanisms
      underlying the transition from solitary living to eusociality, because different
      individuals in the same species can express either eusocial or solitary
      behaviour. A key question is whether alternative social phenotypes represent
      environmentally induced plasticity or predominantly genetic differentiation
      between populations. In this paper, we focus on the sweat bee Lasioglossum
      calceatum, in which northern or high-altitude populations are solitary, whereas
      more southern or low-altitude populations are typically eusocial. To test whether
      social phenotype responds to local environmental cues, we transplanted adult
      females from a solitary, northern population, to a southern site where native
      bees are typically eusocial. Nearly all native nests were eusocial, with
      foundresses producing small first brood (B1) females that became workers. In
      contrast, nine out of ten nests initiated by transplanted bees were solitary,
      producing female offspring that were the same size as the foundress and entered
      directly into hibernation. Only one of these ten nests became eusocial. Social
      phenotype was unlikely to be related to temperature experienced by nest
      foundresses when provisioning B1 offspring, or by B1 emergence time, both
      previously implicated in social plasticity seen in two other socially polymorphic
      sweat bees. Our results suggest that social polymorphism in L. calceatum
      predominantly reflects genetic differentiation between populations, and that
      plasticity is in the process of being lost by bees in northern populations.
      Significance statement: Phenotypic plasticity is thought to play a key role in
      the early stages of the transition from solitary to eusocial behaviour, but may
      then be lost if environmental conditions become less variable. Socially
      polymorphic sweat bees exhibit either solitary or eusocial behaviour in different
      geographic populations, depending on the length of the nesting season. We tested
      for plasticity in the socially polymorphic sweat bee Lasioglossum calceatum by
      transplanting nest foundresses from a northern, non-eusocial population to a
      southern, eusocial population. Plasticity would be detected if transplanted bees
      exhibited eusocial behaviour. We found that while native bees were eusocial, 90%
      of transplanted bees and their offspring did not exhibit traits associated with
      eusociality. Environmental variables such as time of offspring emergence or
      temperatures experienced by foundresses during provisioning could not explain
      these differences. Our results suggest that the ability of transplanted bees to
      express eusociality is being lost, and that social polymorphism predominantly
      reflects genetic differences between populations.

PMID- 29568151
TI  - Continuous laccase concentration in an aqueous two-phase system.
AB  - An approach to describe continuous partitioning of Cerrena unicolor laccase in a
      PEG 6000-phosphate aqueous two-phase system was proposed. The laccase was
      separated from crude supernatant of C. unicolor-submerged culture, and all the
      experiments were carried out in 25  degrees C and pH 7 conditions. Masses of both
      phases and their compositions at phase equilibrium, as well as laccase activity
      concentrations at different mixing points, were measured in batch experiments. An
      empirical short-cut method was developed which allows for calculation of mass and
      volume fractions of the phases, laccase concentration factors, and laccase
      recoveries. Theoretical predictions were verified by several experiments carried
      out in a special mixer-settler unit with automatic substrate feed and continuous
      collection of separated phases. Required concentration of the laccase was
      possible to achieve in a one-step extraction process in the mixer-settler unit.
      The predictions of the short-cut method were compared to the results of
      experimental measurements of phase compositions, phase volume fractions,
      concentration factors and enzymatic yields at steady-state operation of the
      extraction unit. The values of experimental results lay well within the 10% error
      range of the predicted values.

PMID- 29568152
TI  - Comparative PIV and LDA studies of Newtonian and non-Newtonian flows in an
      agitated tank.
AB  - The paper presents results of an experimental study of the fluid velocity field
      in a stirred tank equipped with a Prochem Maxflo T (PMT) type impeller which was
      rotating at a constant frequency of N = 4.1 or 8.2 s-1 inducing transitional (Re
      = 499 or 1307) or turbulent (Re = 2.43 * 104) flow of the fluid. The experiments
      were performed for a Newtonian fluid (water) and a non-Newtonian fluid (0.2 wt%
      aqueous solution of carboxymethyl cellulose, CMC) exhibiting mild viscoelastic
      properties. Measurements were carried out using laser light scattering on tracer
      particles which follow the flow (2-D PIV). For both the water and the CMC
      solution one primary and two secondary circulation loops were observed within the
      fluid volume; however, the secondary loops were characterized by much lower
      intensity. The applied PMT-type impeller produced in the Newtonian fluid an axial
      primary flow, whilst in the non-Newtonian fluid the flow was more radial. The
      results obtained in the form of the local mean velocity components were in
      satisfactory agreement with the literature data from LDA. Distribution of the
      shear rate in the studied system was also analyzed. For the non-Newtonian fluid
      an area was computed where the elastic force dominates over the viscous one. The
      area was nearly matching the region occupied by the primary circulation loop.

PMID- 29568153
TI  - The application of 7H-indolo[1,2-a]quinolinium merocyanine as a new water sensor
      in organic solvents.
AB  - Abstract: The 7H-indolo[1,2-a]quinolinium merocyanine was applied as a new water
      sensor in organic solvents such as ethanol, propane-1-ol, propane-2-ol, DMSO, and
      DMF. The spectral changes of the dye caused by the addition of increasing amount
      of water into an organic solvent were investigated. Based on the results, the
      calibration curves were found as a relation between the position of the
      absorption band of the dye and the water concentration ranging from about 0.05 to
      11% (w/w). In case of ethanol, propane-1-ol and propane-2-ol the plots were
      linear, whereas in DMSO and DMF, better results were obtained with the use of a
      polynomial function. The method allowed to determine the water content in a fast
      and precise manner. Graphical Abstract: 

PMID- 29568154
TI  - Impact of Elevated CO2 and Temperature on Brown Planthopper Population in Rice
      Ecosystem.
AB  - Influence of elevated CO2 (570 +/- 25 ppm) and elevated temperature (?3  degrees
      C higher than ambient) on rice (Oryzasativa L.) and brown planthopper (BPH),
      Nilaparvata lugens (Stal.) was studied in open top chambers during rainy season
      of 2013. Elevated CO2 and temperature exhibited positive effect on BPH
      multiplication thus enhancing its population (55.2 +/- 5.7 hoppers/hill) in
      comparison to ambient CO2 and temperature (25.5 +/- 2.1 hoppers/hill). Elevated
      CO2 + temperature significantly reduced the adult longevity and nymphal duration
      by 17.4 and 18.5 % respectively, however elevated conditions increased BPH
      fecundity by 29.5 %. In rice crop, interactive effect of elevated CO2 and
      temperature led to an increase in the number of tillers (20.1 %) and canopy
      circumference (30.4 %), but resulted in a decrease of reproductive tillers (10.8
      %), seeds/panicle (10.9 %) and 1000-seed weight (8.6 %) thereby reducing grain
      yield (9.8 %). Moreover, positive effect of increased CO2 concentration and
      temperature on BPH population exacerbates the damage (30.6) which in turn coupled
      with the plant traits to hampering production.

PMID- 29568155
TI  - Is there a relationship between the morphology of the forewing axillary sclerites
      and the way the wing folds in aphids (Aphidomorpha, Sternorrhyncha, Hemiptera)?
AB  - The present study describes the relationship between the morphology of the
      forewing axillary sclerites and the way the wings fold among 24 aphid genera as
      compared to a representative of coccids. Architecture of the forewing base was
      imaged with scanning electron and optical (fluorescence) microscopy. Significant
      differences in morphology of axillary sclerites between aphid species were
      observed, despite their belonging to one infraorder. Detailed description of 41
      features of axillary sclerites was made. There was no difference between
      axillaries of viviparous (Aphididae) and oviparous (Adelges sp., Phylloxera sp.)
      species. No clear relationship between morphology of the axillary sclerites and
      the wing folding could be confirmed. Instead, the thorax structure determines the
      way the wing folds in aphids. Phylogenetic analysis based on our results cannot
      be conducted at this stage of study. To show how three-dimensional the structures
      are and how difficult to describe, a short animation of Aphis fabae (Aphididae)
      wing base was added. This is a preliminary study about morphology of axillary
      sclerites among aphids.

PMID- 29568156
TI  - Elytra reduction may affect the evolution of beetle hind wings.
AB  - Beetles are one of the largest and most diverse groups of animals in the world.
      Conversion of forewings into hardened shields is perceived as a key adaptation
      that has greatly supported the evolutionary success of this taxa. Beetle elytra
      play an essential role: they minimize the influence of unfavorable external
      factors and protect insects against predators. Therefore, it is particularly
      interesting why some beetles have reduced their shields. This rare phenomenon is
      called brachelytry and its evolution and implications remain largely unexplored.
      In this paper, we focused on rare group of brachelytrous beetles with exposed
      hind wings. We have investigated whether the elytra loss in different beetle taxa
      is accompanied with the hind wing shape modification, and whether these changes
      are similar among unrelated beetle taxa. We found that hind wings shape differ
      markedly between related brachelytrous and macroelytrous beetles. Moreover, we
      revealed that modifications of hind wings have followed similar patterns and
      resulted in homoplasy in this trait among some unrelated groups of wing-exposed
      brachelytrous beetles. Our results suggest that elytra reduction may affect the
      evolution of beetle hind wings.

PMID- 29568157
TI  - Light Regulates the RUBylation Levels of Individual Cullin Proteins in
      Arabidopsis thaliana.
AB  - In plants, the small protein related to ubiquitin (RUB) modifies cullin (CUL)
      proteins in ubiquitin E3 ligases to allow for efficient transfer of ubiquitin to
      substrate proteins for degradation by the 26S proteasome. At the molecular level,
      the conjugation of RUB to individual CUL proteins is transient in nature, which
      aids in the stability of the cullins and adaptor proteins. Many changes in
      cellular processes occur within the plant upon exposure to light, including well
      documented changes in the stability of individual proteins. However, overall
      activity of E3 ligases between dark- and light-grown seedlings has not been
      assessed in plants. In order to understand more about the activity of the protein
      degradation pathway, overall levels of RUB-modified CULs were measured in
      Arabidopsis thaliana seedlings growing in different light conditions. We found
      that light influenced the global levels of RUBylation on CULs, but not uniformly.
      Blue light had little effect on both Cul1 and Cul3 RUBylation levels. However,
      red light directed the increase in Cul3 RUBylation levels, but not Cul1. This red
      light regulation of Cul3 was at least partially dependent on the activation of
      the phytochrome B signaling pathway. The results indicate that the RUBylation
      levels on individual CULs change in response to different light conditions, which
      enable plants to fine-tune their growth and development to the various light
      environments.

PMID- 29568158
TI  - Degradable, Dendritic Polyols on a Branched Polyphosphazene Backbone.
AB  - Herein, we present the design, synthesis, and characterization of fully
      degradable, hybrid, star-branched dendritic polyols. First multiarmed
      polyphosphazenes were prepared as a star-branched scaffold which upon
      functionalization produced globular branched hydroxyl-functionalized polymers
      with over 1700 peripheral functional end groups. These polyols with unique
      branched architectures could be prepared with controlled molecular weights and
      relatively narrow dispersities. Furthermore, the polymers are shown to undergo
      hydrolytic degradation to low molecular weight degradation products, the rate of
      which could be controlled through postpolymerization functionalization of the
      phosphazene backbone.

PMID- 29568159
TI  - Exploring the Relationship Balance Assessment.
AB  - Assessments of power in couples' relationships often only survey one partner, but
      they do not take into consideration both partners' perceptions. Thus, many
      assumptions about power and equality in relationships have not been
      quantitatively tested due to a lack of dyadic measures of power. Therefore, the
      purpose of the Gender and Relationships Study was to develop and test a new scale
      of equality and relative power for couples, the Relationship Balance Assessment
      (RBA). The RBA may be useful for research and for clinical work with couples to
      help raise awareness of the balance of power in their relationship. A review of
      the literature has shown a shift away from focusing on monetary resources and
      decision-making dominance towards examining relationship processes and the
      connection between gender and power. This study prescreened a pool of process
      oriented questions based on the qualitative literature. Then exploratory factor
      analysis of data from 268 individuals and 91 couples identified 12 consistent
      latent factors underlying relationship equality. These 12 subscales are summed up
      with the TREASURES acronym: Time Discretion, Relational Power, Emotional Power
      (Emotional Expression and Avoidance subscales), Accommodation, Spending and
      Saving subscales, Union or Sexual Dominance, Rational Power, Economic Role Power
      (Status and Childcare subscales), and Social Choices.

PMID- 29568160
TI  - Learning About Parenting Together: A Programme to Support Parents with Inter
      generational Concerns in Pune, India.
AB  - Rapid developments in the last few decades have brought about dramatic changes in
      Indian social life, particularly affecting new middle-class families. Inter
      generational conflicts, high academic pressures, and modern anxieties lead to
      stress both in parents and in children. There is a need for parenting programmes
      that respond to these specific concerns, in order to reduce parenting stress and
      improve family well-being. This study aimed to develop and evaluate a parenting
      programme in Pune, India, based on a 'theory of change'. In this pilot programme,
      parents were encouraged to learn in a group format about fostering autonomy in
      children, promoting academic potential in a stress-free manner and remaining in
      connection with adolescents. Facilitated by a psychologist, parents participated
      in four sessions involving 'creativity and play', 'self-awareness and bonding',
      and 'communication'. The intervention was based on validated psychotherapeutic
      approaches and parenting methods to support parents in their learning. Some 16 in
      depth interviews were conducted with parents before and eight interviews after
      the intervention to understand their learning experiences. Additional feedback
      was gathered from observation notes and debriefings after each session. The
      results show that the attention for playful quality time helped parents to
      (re)gain a more creative and flexible attitude towards spending time with their
      children. Second, parents learned to reflect on their frameworks of meaning
      (rooted in their own upbringing), listen attentively and communicate more mindful
      with their children. Furthermore, this study shows that an activity-based
      approach, connecting parents in co-creating new parenting paradigms, while
      supporting them with stress-reducing tools, is a useful way of engaging this
      target group. The study concludes by offering new perspectives for counsellors
      working with families in countries undergoing rapid change.

PMID- 29568161
TI  - Towards Liquid-Helium-Free, Persistent-Mode MgB2 MRI Magnets: FBML Experience.
AB  - In this article I present our experience at the Magnet Technology Division of the
      MIT Francis Bitter Magnet Laboratory on liquid-helium (LHe)-free, persistent-mode
      MgB2 MRI magnets. Before reporting on our MgB2 magnets, I first summarize the
      basic work that we began in the late 1990s to develop LHe-free, high-temperature
      superconductor (HTS) magnets cooled in solid cryogen-I begin by discussing the
      enabling feature, particularly of solid nitrogen (SN2), for adiabatic HTS
      magnets. The next topic is our first LHe-free, SN2-HTS magnet, for which we chose
      Bi2223 because in the late 1990s Bi2223 was the only HTS available to build an
      HTS magnet. I then move on to two MgB2 magnets, I and II, developed after
      discovery of MgB2 in 2000. The SN2-MgB2 Magnet II-0.5-T/240-mm, SN2-cooled, and
      operated in persistent mode-was completed in January 2016. The final major topic
      in this article is a tabletop LHe-free, persistent-mode 1.5-T/70-mm SN2-MgB2
      "finger" MRI magnet for osteoporosis screening-we expect to begin this project in
      2017. Before concluding this article, I present my current view on challenges and
      prospects for MgB2 MRI magnets.

PMID- 29568162
TI  - The transitional dynamics of caloric ecosystems: changes in the food supply
      around the world.
AB  - Changes to the global food supply have been characterized by greater availability
      of edible oils, sweeteners, and meats-a profound "nutrition transition"
      associated with rising obesity, type 2 diabetes, and cardiovascular disease.
      Through an analysis of three longitudinal databases of food supply, sales and
      economics across the period 1961-2010, we observed that the change in global food
      supply has been characterized by a dramatic rise in pig meat consumption in China
      and poultry consumption in North America. These changes have not been experienced
      by all rapidly-developing countries, and are not well explained by changes in
      income. The changes in food supply include divergence among otherwise similar
      neighboring countries, suggesting that the changes in food supply are not an
      inevitable result of economic development. Furthermore, we observed that the
      nutrition transition does not merely involve an adoption of "Western" diets
      universally, but can also include an increase in the supply of edible oils that
      are uncommon in Western countries. Much of the increase in sales of sugar
      sweetened beverages and packaged foods is attributable to a handful of
      multinational corporations, but typically from products distributed through
      domestic production systems rather than foreign importation. While North America
      and Latin America continued to have high sugar-sweetened beverage and packaged
      food sales in recent years, Eastern Europe and the Middle East have become
      emerging markets for these products. These findings suggest further study of
      natural experiments to identify which policies may mitigate nutritional risk
      factors for chronic disease in the context of economic development.

PMID- 29568163
TI  - We are back... On time.... Striving to be better....

PMID- 29568164
TI  - Collaborations with international speciality organisations.

PMID- 29568166
TI  - Expression of protease-activated receptors 1 and 2 in individuals with healthy
      gingiva and chronic periodontitis.
AB  - Background: Protease-activated receptors (PAR-1 and PAR-2) are found to be
      immensely exhibited in the periodontal tissues. These receptors are involved in
      the inflammatory and repair processes. Activation of PARs is mainly by the
      bacterial and endogenous enzymes. The aim of the study was to determine the role
      of PAR-1 and PAR-2 in initiating periodontal inflammation and to immunolocalize
      these receptors in the gingival tissues of healthy and chronic periodontitis
      individuals. Materials and Methods: A total of 50 patients were selected for this
      study, of which 25 were healthy controls and 25 were chronic periodontitis
      patients. Gingival tissues were excised from the marginal gingiva and interdental
      papilla under local anesthesia (xylocaine with 2% adrenaline) during crown
      lengthening procedure or during periodontal therapy depending on the respective
      groups. Immunohistochemical analyses of PARs were done by staining the samples
      with hematoxylin and eosin and with primary and secondary antibody for PAR-1 and
      PAR-2. Results: The Hematoxylin and Eosin staining showed more inflammatory
      changes in the periodontitis group compared to healthy gingiva. In chronic
      periodontitis, PAR-1-positive cells were seen in the basal layer with a weak
      expression and were showing negative expression in the superficial layer. In
      consideration of PAR-2, there was a very strong expression up to the superficial
      layer of the epithelium, compared to PAR-1. On comparing the intensity of
      staining in the connective tissue of chronic periodontitis sample, there was an
      increased expression of PAR-2 compared with PAR-1. A low positive expression of
      PAR-1 and PAR-2 was observed in the epithelium and connective tissue of the
      healthy tissues. Conclusion: The results clearly demonstrated the role of PAR-1
      and 2 in periodontal inflammation.

PMID- 29568165
TI  - Periodontal microsurgery: Reaching new heights of precision.
AB  - The use of magnification to perform various procedures in medical and dental
      field, particularly endodontics has long been recognized. Unfortunately, its
      application in periodontics is not widely popularized. The objective of this
      article is to emphasize the application of microsurgical principles in various
      periodontal surgical procedures and to reinforce the incorporation of microscope
      into periodontal practice. The most recent periodontal journals were reviewed and
      a search of databases such as PubMed or Medline and Google Scholar was conducted
      for relevant material from published literature up to 2017. Medical Subject
      Headings words looked for were "periodontal microsurgery" and "minimally invasive
      periodontal surgery." The available literature, specifically to periodontal
      surgical procedures was analyzed and compiled. The analysis indicates that
      incorporation of magnification in periodontal practice is associated with
      improved visual acuity, ergonomic benefits, decreased patient morbidity, rapid
      healing, and enhanced patient acceptance.

PMID- 29568167
TI  - Efficiency of three different polishing methods on enamel and cementum: A
      scanning electron microscope study.
AB  - Background: Tooth polishing is an integral part of clinical dentistry. The main
      purpose of polishing is to smoothen the surface of the tooth and minimize the
      deposition of plaque to allow a healthy periodontal maintenance postscaling.
      Today, polishing by different methods is available to a clinician. Traditional
      bristle brush and rubber-cup polishing are being widely practiced and gradually
      getting replaced by novel air polisher. Pros and cons of each method should be
      weighed before its clinical applications. Aim and Objectives: To evaluate and
      compare the efficiency of three different polishing systems on enamel as well as
      on cementum surfaces by scanning electron microscope (SEM). Materials and
      Methods: A total of 120 samples were divided into three groups randomly - Group 1
      (bristle brush), Group 2 (rubber cup), and Group 3 (air polisher) - with 20
      samples each of enamel and cementum, which were subdivided into 10 control and 10
      test group (subjected to polishing). The samples were analyzed by SEM at *1000
      magnification, and the data obtained were compiled and subjected to statistical
      analysis. Results: Polishing with bristle brush demonstrated less surface
      roughness and debris when compared to air polisher at P = 0.58, P = 0.03 for
      enamel surface and P = 0.003, P = 0.21 for cementum, respectively. The surface
      roughness was reduced considerably by rubber cup at P = 0.03 for enamel and P =
      0.003 for cementum, compared to air polisher at P = 0.99 and P = 0.21 for enamel
      and cementum, respectively. Conclusion: The results indicate that polishing with
      rubber cup was more effective and statistically significant when compared to
      bristle brush polishing and air polisher for the crown and root surface
      smoothening and debris removal.

PMID- 29568168
TI  - Periostin levels in saliva of patients with chronic periodontitis.
AB  - Background: Periostin acts as a necessary protein for tissue integrity and
      maturity and has a key role as a modulator of periodontal ligament hemostasis. It
      has been shown that periostin acts as a supportive protein. The aim of this study
      was to compare the concentration of periostin in the saliva of patients with
      chronic periodontitis and healthy controls. Materials and Methods: In this case
      control, cross-sectional study, a total of 45 individuals (25 patients with
      chronic periodontitis and 20 healthy controls) were evaluated. Whole saliva
      samples were collected, and periostin levels were evaluated by standard enzyme
      linked immunosorbent assay. The results were analyzed by SPSS and Mann-Whitney
      analysis. Results: The results of this study showed that the level of periostin
      in saliva in patients with periodontitis was significantly lower than healthy
      controls (P < 0.05). Periostin was detectable in all samples. Conclusion: The
      results show that there is a significant relationship between the level of
      periostin in saliva and chronic periodontitis. Periostin may be considered as an
      inflammatory marker in periodontal disease. However, further studies are needed
      to confirm this finding.

PMID- 29568169
TI  - Efficacy of Ayurvedic drugs as compared to chlorhexidine in management of chronic
      periodontitis: A randomized controlled clinical study.
AB  - Background: In India, Ayurveda is considered to be more effective and cheaper
      than modern medicine. Ayurvedic literature shows its use in treating oral
      diseases also. However, their effectiveness, in comparison with the allopathic
      mode of management, has not been assessed previously. The aim of this randomized
      controlled clinical trial was to compare the efficacy of ayurvedic drugs over
      chlorhexidine in treating chronic periodontitis. Materials and Methods: Four
      hundred and eight participants, in the age group 20-49 years, suffering from mild
      to-moderate chronic periodontitis were included in this study. Community
      periodontal index for treatment needs (CPITN) score was recorded, and oral
      prophylaxis was done for each patient. They were then randomly divided into 6
      groups: control group (I), chlorhexidine (II), Khadiradi vati (III),
      Dashansanskar churana (IV), Neem (V), and Apamarga (VI); based on the drugs used
      by patients for the maintenance of oral hygiene after oral prophylaxis. Patients
      were recalled at 1 week, 1 month, and 3 months after oral prophylaxis. CPITN
      score was re-recorded for each patient at each follow-up. Reduction in CPITN
      score indicated improvement in the periodontal health. Observations were
      statistically analyzed using univariate ANOVA and P value was set at <0.5.
      Results: Improvement in CPITN scores in 6 groups was as follows: I - 42.0%, II -
      76.37%, III - 82.03%, IV - 83.46%, V - 78.8%, and VI - 29.9%. Higher mean
      percentage improvement was seen when patients used these drugs for 3 months as
      compared to 1 month. Conclusion: Dashansanskar churana and Khadiradi vati showed
      better results than chlorhexidine and were found to be superior in managing mild
      to-moderate cases of chronic periodontitis.

PMID- 29568170
TI  - Effectiveness of three mouthwashes - Manuka honey, Raw honey, and Chlorhexidine
      on plaque and gingival scores of 12-15-year-old school children: A randomized
      controlled field trial.
AB  - Objectives: The aim of this study is to compare the effectiveness of three types
      of mouthwashes manuka honey (MH), raw honey (RH), and chlorhexidine (CHX) on
      plaque and gingival scores of 12-15-year-old government school children. Study
      Design: This study was a double-blind, randomized controlled field trial
      conducted in Belagavi city, India. Materials and Methods: One hundred and thirty
      five government school children aged 12-15 years were randomly selected and
      allocated into three groups, RH, MH, and CHX mouthwash groups. Ten milliliters
      each of honey-based mouthwash formulation and CHX mouthwashes (0.2%) were
      administered according to the group allocation twice daily for 21 days. All the
      children were examined at baseline, 22nd day (after discontinuation of mouthwash)
      and 28th day (1 week after discontinuation of mouthwash) for Gingival (Loe and
      silness 1963) and Plaque Index (Silness and Loe, 1964). Results: Descriptive
      statistics was applied for distribution of study participants according to age
      and gender. One-way ANOVA followed by Tukey's post hoc test and repeated measures
      ANOVA test followed by Bonferroni's post hoc were applied for inter- and
      intragroup comparison, respectively. Statistically significant reductions (P <
      0.001) in plaque and gingival scores were observed in all the three types of
      mouthwash groups at the end of the 22nd day and 28th day. MH and RH mouthwash
      demonstrated equal effectiveness, whereas CHX mouthwash showed the maximum
      reduction in clinical parameters. Conclusion: Honey-based mouthwash showed a
      promising antimicrobial effect on dental caries and plaque and gingival scores.

PMID- 29568171
TI  - Effect of scaling and root planing on gingival crevicular fluid level of YKL-40
      acute phase protein in chronic periodontitis patients with or without type 2
      diabetes mellitus: A clinico-biochemical study.
AB  - Background: The aim of the present study was to evaluate the gingival crevicular
      fluid (GCF) levels of YKL-40 acute phase protein in chronic periodontitis (CP)
      with and without type 2 diabetes and also to assess the effect of periodontal
      therapy (scaling and root planing [SRP]) on this GCF biomarker and the clinical
      parameters. YKL-40 is derived from tyrosine (Y), lysine (K), and leucine (L) with
      a molecular weight of 40 kDa. Materials and Methods: A total of 105 individuals
      (30-60 years) were grouped as 35 individuals each in three groups (Group I -
      healthy; Group II - CP with diabetes mellitus [DM]; and Group III - CP). Clinical
      parameters including plaque index, gingival index, probing pocket depth, and
      clinical attachment level followed by GCF sample collection from test sites were
      done at baseline and 6 weeks after SRP (among Group II and Group III patients).
      GCF YKL-40 level was determined by enzyme-linked immunosorbent assay. Results:
      The mean GCF YKL-40 level at baseline was significantly lower for Group I (309.81
      +/- 124.93 pg/ml) as compared to Group II (924.88 +/- 415.28 pg/ml) and Group III
      (834.08 +/- 270.42 pg/ml), respectively (P < 0.001). The level reduced
      significantly 6 weeks after SRP for Group II (507.6 +/- 265.03 pg/ml) and Group
      III (499.54 +/- 293.38 pg/ml) (P < 0.001). Conclusion: The level of GCF YKL-40 in
      CP patients with or without DM is higher than healthy individuals and the level
      reduced 6 weeks post-SRP among Group II and Group III. Hence, YKL-40 can be
      considered as an important biomarker in the diagnosis of CP.

PMID- 29568172
TI  - Treatment of gingival recession by coronally advanced flap in conjunction with
      platelet-rich fibrin or resin-modified glass-ionomer restoration: A clinical
      study.
AB  - Aims: The aim of this study is to compare the outcome of coronally advanced flap
      (CAF) along with the use of platelet-rich fibrin (PRF) versus CAF in conjunction
      with a resin-modified glass-ionomer cement (RmGIC) for the management of Millers
      Class I and Class II gingival recession coupled with noncarious cervical lesions
      (NCCLs). Materials and Methods: Single and multiple Miller's Class I and Class II
      gingival recessions were chosen for the study. Twenty participants with total of
      78 sites associated with NCCL bilaterally in the anterior and premolar region of
      maxilla were selected. Thirty-nine sites were treated with CAF and PRF and the
      remaining 39 sites were treated with CAF and RmGIC. Clinical parameters such as
      probing pocket depth, relative gingival recession, relative clinical attachment
      level, NCCL height, NCCL width, width of keratinized tissue, and keratinized
      tissue thickness were measured at baseline, 90th, and 180th day in both the
      groups. The presence or absence of dentin sensitivity (DS) was determined at
      baseline and 180th day. Results: Both the groups showed optimal root coverage,
      with statistical significant difference in thickness of keratinized gingiva in
      Group I when compared to Group II from baseline to 90th day and from baseline to
      180th day and also from 90th to 180th day. On comparing the DS between Group I
      and Group II from baseline to 180th day, Group II showed greater reduction in
      dentinal hypersensitivity as compared to Group I. Conclusion: The use of PRF
      along with CAF showed increased thickness of the keratinized tissue and the
      utilization of RmGIC resulted in decreased DS. Hence, the combination of CAF and
      PRF or CAF and RmGIC could provide a better treatment option in the management of
      gingival recession that is of esthetic concern.

PMID- 29568173
TI  - Maternal periodontal disease and preeclampsia in Jaipur population.
AB  - Background: Preeclampsia is identified as an important cause for mother and
      newborn mortality. Inspite of extensive research, the exact etiological relations
      have not been established. Hence, an attempt has been made in this study to
      evaluate the relationship between the preeclampsia and maternal periodontal
      disease. Materials and Methods: The case-control study comprised of thirty
      pregnant women distributed equally in the case (preeclampsia) and control
      (healthy) group. Gingival index, plaque index, bleeding on probing, clinical
      probing depth, and clinical attachment level were measured in both groups.
      Microbiologic examination for identification of one red complex organism
      Porphyromonas gingivalis and one orange complex organism Fusobacterium nucleatum
      were done in plaque and placental blood of cases and controls. The clinical
      examinations and collection of placental blood were done 24 h before delivery.
      Results: Periodontal condition in the preeclamptic women was statistically worse
      compared with the normotensive women. There was no statistically significant
      association between microorganisms in plaque and placental blood between
      normotensive control and preeclamptic pregnant women. The preeclamptic women had
      significantly higher chances of having newborns weighing <2.5 kg than the
      normotensive women. Conclusion: The preeclamptic women were associated with
      significantly higher periodontitis and lower fetal birth weight than normotensive
      women.

PMID- 29568174
TI  - Oral hygiene and periodontal status in the primitive hidden tribe of Patalkot, a
      tribal area in Central India.
AB  - Introduction: Very little is known about the hard to reach tribal communities in
      India and one such community is a primitive hidden and isolated tribe group of
      Bharia people in Patalkot. Their health problems need special attention as they
      have very limited access to health care. The aim of this study is to assess the
      oral hygiene and periodontal status in the primitive tribe group of Bharias in
      Patalkot, Madhya Pradesh, India. Materials and Methods: A descriptive cross
      sectional study was undertaken with sample size of 462 patients. The sample was
      selected using simple random technique. A predefined pro forma was used to record
      information about oral hygiene practices and tobacco-related habits. Oral Hygiene
      Index-simplified (OHI-S), Community Periodontal Index (CPI), and loss of
      attachment (LOA) were used to assess oral hygiene and periodontal status,
      respectively. Results: The prevalence of periodontal disease based on CPI scores
      showed that 35.4 % had periodontal pocket > 6mm. It was also found that 27.9%
      people had attachment loss of 6-8mm. Mean Debris Index-simplified, Calculus Index
      simplified, and OHI-S for the participants were 1.59 +/- 0.73, 0.99 +/- 0.70, and
      2.56 +/- 1.36, respectively. Poor oral hygiene status was found in 36.3% of
      Bharias. Conclusion: Higher prevalence of periodontal diseases and poor oral
      hygiene status in Bharia people can be attributed mainly to their difficult
      terrain, isolation, very low literacy level, socioeconomic status, and cultural
      practices.

PMID- 29568175
TI  - Management of a granulomatous lesion in a patient with Kindler's Syndrome.
AB  - Kindler's syndrome is a rare vesiculobullous dermatological disorder sometimes
      involving multiple organs. First described by Kindler. The differential diagnosis
      includes Rothmund-Thomson syndrome and epidermolysis bullosa. Fisher's criteria
      have simplified the diagnosis with major and minor criteria. Oral manifestation
      of this syndrome includes multiple painful oral ulcers in the mucosa, periodontal
      attachment loss, gingival bleeding, and fragile mucosa. These manifestations may
      impair proper nutrition intake, may cause growth and development problems. This
      case report deals with the management of oral and gingival manifestations in a 12
      year-old female child patient diagnosed with Kindler's syndrome.

PMID- 29568176
TI  - Interdisciplinary approach to enhance the esthetics of maxillary anterior region
      using soft- and hard-tissue ridge augmentation in conjunction with a fixed
      partial prosthesis.
AB  - Favorable esthetics is one of the most important treatment outcomes in dentistry,
      and to achieve this, interdisciplinary approaches are often required. Ridge
      deficiencies can be corrected for both, soft- and hard-tissue discrepancies. To
      overcome such defects, not only a variety of prosthetic options are at our
      disposal but also several periodontal plastic surgical techniques are available
      as well. Various techniques have been described and revised, over the year to
      correct ridge defects. For enhancing soft-tissue contours in the anterior region,
      the subepithelial connective tissue graft is the treatment of choice. A
      combination of alloplastic bone graft in adjunct to connective tissue graft
      optimizes ridge augmentation and minimizes defects. The present case report
      describes the use of vascular interpositional connective tissue graft in
      combination with alloplastic bone graft for correction of Seibert's Class III
      ridge deficiency followed by a fixed partial prosthesis to achieve a better
      esthetic outcome.

PMID- 29568177
TI  - Multidisciplinary prognostic transition of a molar tooth for long-term survival.
AB  - Patients with periodontitis may have one or few teeth with hopeless prognosis,
      which would have to be extracted before initiation of orthodontic therapy.
      Periodontal therapy aims to prolong the lifespan of dentition, as preserving
      natural dentition is always the best treatment option. The decision to retain a
      tooth is always based on the probability of long-term success of one or more
      treatment modality. A 17-year-old female patient seeking fixed orthodontic
      treatment presented with the left mandibular first molar tooth (36) having
      hopeless periodontal prognosis with advanced primary periodontal and secondary
      endodontic lesion, grade III mobility, and grade II furcation involvement. Root
      canal treatment followed by periodontal surgery using a combination of bone graft
      (allograft) and platelet-rich fibrin membrane resulted in a clinical and
      radiographic indication of periodontal healing. The tooth (36) was even used for
      orthodontic anchorage 3-month postsurgically and was maintained for 2 years.
      Appropriate diagnosis and meticulous multidisciplinary treatment approach can
      lead to the restoration of health and function of the teeth with severe loss of
      attachment and bone loss and can even be used for orthodontic anchorage.

PMID- 29568178
TI  - Triangular coronally advanced flap: Conventional versus Microsurgery.
AB  - Several surgical techniques including pedicle flaps and free soft-tissue grafts
      have been indicated for the treatment of gingival recession defects with
      different success rates. Localized gingival recessions can be managed with
      various root coverage procedures, more specifically, using the coronally advanced
      flap with distinct designs. Predictable and consistent periodontal plastic
      surgical results can be achieved by using microsurgical instruments. Periodontal
      microsurgery involves the use of magnifying devices, microsurgical instruments,
      and materials in existing basic surgical techniques. It offers definitive
      advantages in terms of predictability, postoperative morbidity, and patient
      approval. This case report aims at comparing the modified approach with a
      triangular type of coronally advanced flap, using conventional and microsurgical
      approach, for treating bilateral isolated Miller's class I defect in both the
      maxillary canines by a split-mouth design.

PMID- 29568179
TI  - Management of multiple recession defects in esthetic zone using platelet-rich
      fibrin membrane: A 36-month follow-up case report.
AB  - A patient undergoing orthodontic treatment presented with multiple recession
      defects in maxillary anterior region. After thorough clinical examination and
      assessment, measurements were recorded. Maxillary anterior teeth with recession
      defects of 3-4 mm were treated with coronally advanced flap and platelet-rich
      fibrin (PRF) membrane. Regular follow-up was maintained for the patient at 3, 6 ,
      12, 18, 24, 30, and 36 months. After 36 months, significant root coverage of 100
      percent was observed in four defects and 50% coverage in one defect. This shows
      that PRF membrane along with coronally advanced provides a predictable and
      significant result for management of recession defects.

PMID- 29568180
TI  - Alleviation of Heat Stress by a Polyherbal Formulation, PhytoceeTM: Impact on
      Zootechnical Parameters, Cloacal Temperature, and Stress Markers.
AB  - Background: The range of thermoneutral zone of chickens is narrow, and they
      become easily susceptible to environmental stress, a common and major concern for
      poultry causing a production loss. Objective: The present study was designed to
      comparatively evaluate anti-stress activity of PhytoceeTM and Vitamin C in
      chickens reared under heat stress. Materials and Methods: A total of 600-day-old
      chicks of Cobb 400 were randomly assigned to 4 groups with 6 replicates
      comprising 25 birds each (n = 150). G1 served as a normal control (NC) and
      supplemented with Vitamin C at 100 g/ton of feed. G2 served as a heat stress
      control (HSC), subjected to heat stress (34 degrees C-36 degrees C) without
      Vitamin C supplementation. G3 and G4 served as positive control and treatment
      group (TC), subjected to heat stress and supplemented with Vitamin C and
      PhytoceeTM at 100 g/ton of feed, respectively. The impact on zootechnical
      parameters and cloacal temperature was assessed at regular intervals, and blood
      was collected at the end of the experiment for evaluation of stress parameters,
      namely heterophil lymphocyte ratio (H:L ratio) and serum corticosterone. Results:
      Exposure of chickens to heat stress caused a significant decrease in body weight,
      worsening of feed conversion ratio, higher mortality, and poor production
      efficiency. Moreover, serum corticosterone level, H:L ratio, and cloacal
      temperature were significantly increased in HSC as compared to NC. However,
      supplementation of PhytoceeTM in feed significantly ameliorated the negative
      impact of heat stress in broiler birds. Conclusion: The supplementation of
      PhytoceeTM demonstrated an anti-stress effect in chickens through restoration of
      serum corticosterone level, H:L ratio, and thermoregulatory mechanism. SUMMARY:
      Combating heat stress remains a challenge for the broiler industry in the tropics
      and subtropics, which is even aggravated by the changing climatic conditionsThe
      present study was designed to evaluate the anti-stressor activity of PhytoceeTM,
      a polyherbal formulation containing Emblica officinalis, Ocimum sanctum, and
      Withania somnifera in broiler using heat stress model in comparison with Vitamin
      CPhytoceeTM demonstrated an anti-stress effect in the current study by
      ameliorating the negative effects of heat stress on zootechnical parameters,
      serum corticosterone, heterophil lymphocyte ratio, and cloacal temperature of
      broilers through modulating the hypothalamic-pituitary-adrenal axis and
      thermoregulatory mechanismHence, PhytoceeTM could be recommended in broilers and
      livestock animals for modulating and combating adverse effects of heat stress and
      thereby reducing the economic losses incurred by farmers. Abbreviations Used: HPA
      axis: Hypothalamic pituitary adrenal axis.

PMID- 29568182
TI  - Quantitative Phytochemical Constituents and Antioxidant Activities of the
      Mistletoe, Phragmanthera capitata (Sprengel) Balle Extracted with Different
      Solvents.
AB  - Objective: The investigation aimed to evaluate the in vitro quantitative
      phytochemical compositions and antioxidant capacity of the dried leaves of
      Phragmanthera capitata extracted with different solvents. Methodology: Different
      phytochemical assays were used to evaluate the phenols, flavonoids, and
      proanthocyanidin contents of the acetone, methanol, ethanol, and aqueous extracts
      of the sample. Antioxidant activity was measured using 2,2diphenyl-1
      picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)
      (ABTS), Ferric reducing antioxidant power (FRAP), nitric oxide, and total
      antioxidant capacity (TAC) assays. Results: Methanol had the highest extraction
      yield (21.50%) followed by aqueous (10.87%). Acetone and ethanol yielded 6.87%
      and 4.3%, respectively. However, acetone and ethanol extracts had more phenolic
      content (218.6 +/- 3.38 and 214.8 +/- 3.56 mg gallic acid equivalent (GAE)/g,
      respectively) that were significantly higher (P < 0.05) than the methanol and
      aqueous extracts (203.8 +/- 1.95 and 175.5 +/- 0.32 mg GAE/mg, respectively).
      Acetone extract also had more flavonoid and proanthocyanidin contents (679.8 +/-
      6.26 mg quercetin equivalent/g and 645.7 +/- 6.35 mg catechin equivalent/g,
      respectively) that were significantly higher than the other solvent extracts (P <
      0.05). All the solvent fractions showed great antioxidant activities with the
      acetone fraction having the highest capacity based on ABTS, DPPH, and TAC assays
      (half maximal inhibitory concentration [IC50] = <5 MUg/mL, 24.5 MUg/mL, and 85
      MUg/mL respectively). The methanol extract however had FRAP and nitric oxide
      antioxidant activities (IC50 = 302 MUg/mL and < 25 MUg/mL respectively).
      Conclusion: The findings of this study provide evidence that P. capitata has
      potential as a natural source of antioxidant with acetone showing to be the best
      extractant of the polyphenolics with corresponding higher antioxidant activities.
      SUMMARY: The study investigated the in vitro polyphenolic content and antioxidant
      activities of the mistletoe; Phragmanthera capitata, extracted with different
      solventsThe resultant outcome of the study showed that while methanol had more
      yield from the extraction, the highest polyphenolic contents was observed in the
      acetone extractThe acetone extract also showed the highest antioxidant activity
      in most of the assaysThere was a positive correlation between the polyphenolics
      and the antioxidant activities: Higher polyphenol content resulted in a better
      antioxidant activityIf extracting this plant for preparatory works only, methanol
      would be preferred, but if it were for bioassay screening, acetone will be the
      solvent of choice. Abbreviations Used: DPPH: 2, 2diphenyl-1-picrylhydrazyl
      (DPPH)ABTS: 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)FRAP: Ferric
      reducing antioxidant powerTAC: Total antioxidant capacityGAE: Gallic acid
      equivalentQE: Quercetin equivalentCE: Catechin equivalentBHT: Butylated hydroxyl
      toluene.

PMID- 29568181
TI  - Cytotoxic Compounds from Wrightia pubescens (R.Br.).
AB  - Background: Mixtures of ursolic acid (1) and oleanolic acid (2) (1:1 and 1:2),
      oleanolic acid (2), squalene (3), chlorophyll a (4), wrightiadione (5), and alpha
      amyrin acetate (6) were isolated from the dichloromethane (CH2 Cl2) extracts of
      the leaves and twigs of Wrightia pubescens (R.Br.). Objectives: To test for the
      cytotoxicity potentials of 1-6. Materials and Methods: The antiproliferative
      activities of 1-6 against three human cancer cell lines, breast (MCF-7) and colon
      (HT-29 and HCT-116), and a normal cell line, human dermal fibroblast neonatal
      (HDFn), were evaluated using the PrestoBlue(r) cell viability assay. Results:
      Compounds 4, 1 and 2 (1:2), 2, 1 and 2 (1:1), and 5 exhibited the most cytotoxic
      effects against HT-29 with half maximal inhibitory concentration (IC50) values of
      0.68, 0.74, 0.89, 1.70, and 4.07 MUg/mL, respectively. Comparing 2 with its 1:1
      mixture with 1 (IC50 = 1.70 and 7.18 MUg/mL for HT-29 and HCT-116, respectively)
      and 1:2 mixture with 1 (0.74 and 3.46 MUg/mL for HT-29 and HCT-116,
      respectively), 2 also showed strong cytotoxic potential against HT-29 and HCT-116
      (0.89 and 2.33 MUg/mL, respectively). Unlike the mixtures which exhibited low
      effects on MCF-7 (IC50 = 20.75 and 30.06 MUg/mL for 1:1 and 1:2, respectively), 2
      showed moderate activity against MCF-7 (10.99 MUg/mL). Compound 6 showed the
      highest cytotoxicity against HCT-116 (IC50 = 4.07 MUg/mL). Conclusion: Mixtures
      of 1 and 2 (1:1 and 1:2), 2, 3, 4, 5, and 6 from the CH2 Cl2 extracts of the
      leaves and twigs of W. pubescens (R.Br.) exhibited varying cytotoxic activities.
      All the compounds except 6 exhibited the strongest cytotoxic effects against HT
      29. On the other hand, 6 was most cytotoxic against HCT-116. Overall, the
      toxicities of 1-6 were highest against HT-29, followed by HCT-116 and MCF-7. All
      the compounds showed varying activities against HDFn (IC50 < 30 MUg/mL). SUMMARY:
      Mixtures of ursolic acid (1) and oleanolic acid (2) (1:1 and 1:2), oleanolic acid
      (2), squalene (3), chlorophyll a (4), wrightiadione (5), and alpha-amyrin acetate
      (6), isolated from the dichloromethane extracts of the leaves and twigs of
      Wrightia pubescens (R.Br.), showed varying cytotoxic activities against three
      human cancer cell lines, breast (MCF-7) and colon (HT-29 and HCT-116), and a
      normal cell line, human dermal fibroblast-neonatal (HDFn), as evaluated using the
      PrestoBlue(r) cell viability assay.Abbreviation Used: IC50: Half maximal
      inhibitory concentration.

PMID- 29568183
TI  - Algae from Portuguese Coast Presented High Cytotoxicity and Antiproliferative
      Effects on an In vitro Model of Human Colorectal Cancer.
AB  - Background: The marine environment has shown to be an interesting source of new
      antitumor agents, representing an important tool in cancer research. Objective:
      The aim of this study was to evaluate the antitumor activities of 12 algae from
      Peniche coast (Portugal) on an in vitro model of human colorectal cancer (Caco-2
      cells). Materials and Methods: The antitumor potential was accessed by evaluating
      Caco-2 cell's viability and proliferation through the 3-[4, 5-dimethylthiazol-2
      yl]-2, 5-diphenyl tetrazolium bromide and calcein-AM methods. Results: The
      dichloromethane extracts of Asparagopsis armata and Sphaerococcus coronopifolius
      induced the highest decrease on cell's viability (1 mg/mL; 24 h), 98.96% +/-
      0.39% and 98.08% +/- 0.89%, respectively, followed by the methanolic extracts of
      S. coronopifolius (96.47% +/- 1.26%) and A. armata (92.68% +/- 1.17%). Regarding
      cell proliferation, the highest decrease of Caco-2 cell's proliferation (1 mg/mL;
      24 h) was induced by the dichloromethane extract of A. armata (100% +/- 0.48%),
      S. coronopifolius (99.04 +/- 0.51%), and Plocamium cartilagineum (95.05% +/-
      1.19%). The highest potency was shown by the dichloromethane extract of S.
      coronopifolius in both, cytotoxicity and antiproliferative tests, with an IC50 of
      21.3 and 36.5 MUg/mL, respectively. Conclusion: The extracts of A. armata and S.
      coronopifolius are promising sources of new bioactive molecules with application
      in cancer therapeutics. SUMMARY: Algae from Peniche coast (Portugal) revealed to
      be a promising source of new bioactive compounds with potential application on
      cancer therapeutics. Abbreviations Used: MTT: 3-[4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyl tetrazolium bromide; DMSO: Dimethyl sulfoxide; FBS: Fetal bovine serum;
      MEM: Minimum Essential Medium; SEM: Standard error of the mean;SP : Sulfated
      polysaccharides.

PMID- 29568184
TI  - Antioxidant Activities of Basella alba Aqueous Leave Extract In Blood, Pancreas,
      and Gonadal Tissues of Diabetic Male Wistar Rats.
AB  - Background: Oxidative stress is frequently identified as a key element in the
      pathophysiology of many complications of diabetes mellitus, including
      reproductive complications. The antioxidant potential of medicinal plants have
      been suggested for therapeutic focus of diseases in recent reports. Objective: To
      investigate the effect of Basella alba (Ba) aqueous leave extract on diabetes
      induced oxidative stress. Materials and Methods: Forty male Wistar rats (8-10
      weeks) were randomly divided into four groups (n = 10) and treated as follows;
      Control (C + Ns) and Diabetic (D + Ns) animals received oral normal saline 0.5
      ml/100 g body weight daily, while Healthy Treatment (H + Ba) and Diabetic
      Treatment (D + Ba) rats were given Ba extract at an oral dose of 200 mg/kg body
      weight daily. Treatment was by gavage and lasted 4 weeks in all groups. Diabetes
      was induced in D + Ns and D + Ba rats by single intraperitoneal injection of
      streptozotocin (55 mg/kg) and fasting blood sugar (FBS) recorded weekly in all
      rats afterwards. Animals were euthanized at the end of the experiment and blood
      samples, pancreas, testes, and epididymis were preserved for analysis of
      oxidative stress biomarkers. Results: Oral administration of aqueous leave
      extract of Ba significantly (P < 0.0001) lowered FBS in D + Ba rats. There was
      significantly higher blood superoxide dismutase activity and serum ferric
      reducing antioxidant power, but lower serum concentration of conjugated dienes
      and thiobarbituric acid reactive substances in D + Ba compared to D + Ns rats (P
      < 0.05). Conclusion: Ba exerts antioxidant effects in the gonads by enhancing
      antioxidant parameters in circulating blood, but not necessarily in the gonadal
      tissues. SUMMARY: Oral treatment of diabetic rats with aqueous leave extract of
      Basella alba exerts antioxidant effects in the gonads by enhancing antioxidant
      parameters in circulating blood, but not necessarily in the gonadal tissues.
      Abbreviations Used: AP - Antioxidant parameters, Ba - Basella alba, CAT -
      Catalase, CDs - Conjugated dienes, DM - Diabetes mellitus, FBS - Fasting blood
      sugar, FRAP - Ferric reducing antioxidant power, GSH - reduced glutathione, Ns -
      Normal saline, ORAC - oxygen radical antioxidant capacity, RNS - reactive
      nitrogen species, ROS - reactive oxygen species, SOD - superoxide dismutase, TAC 
      Total antioxidant capacity, TBARS - thiobarbituric acid reactive substances,
      TEAC - trolox equivalent antioxidant capacity.

PMID- 29568185
TI  - Thermogenic Blend Alone or in Combination with Whey Protein Supplement Stimulates
      Fat Metabolism and Improves Body Composition in Mice.
AB  - Background: Certain food ingredients promote thermogenesis and fat loss.
      Similarly, whey protein improves body composition. Due to this potential
      synergistic effect, a blend of thermogenic food ingredients containing African
      mango, citrus fruit extract, Coleus forskohlii, dihydrocapsiate, and red pepper
      was tested alone and in combination with a whey protein supplement for its
      effects on body composition in sedentary mice during high-fat diet. Objective:
      The objective of this study was to evaluate the interaction of thermogenic foods
      on improving body composition during consumption of an unhealthy diet. Materials
      and Methods: C57BL/6J young adult male mice (n = 12) were placed on a 60% high
      fat diet for 4 weeks and subsequently randomly assigned to receive daily dosing
      by oral gavage of vehicle, the novel blend alone or with whey protein supplement
      for another 4 weeks. Body composition, thermal imaging of brown adipose tissue
      (BAT), mitochondrial BAT uncoupling protein 1 (UCP1), and plasma levels of leptin
      were assessed. Results: Novel blend alone and in combination with protein
      supplement attenuated body weight gain, fat, and increased surface BAT
      temperature in comparison to vehicle control and to baseline (P < 0.5). The
      combination of novel blend and whey protein supplement also significantly
      increased UCP1 protein expression in BAT mitochondria in comparison to vehicle
      control and novel blend alone (P < 0.5). Conclusions: These data indicate that
      this novel blend stimulates thermogenesis and attenuates the gain in body weight
      and fat in response to high-fat diet in mice and these effects were improved when
      administered in combination with whey protein supplement. SUMMARY: 30 days oral
      administration to mice of a novel blend containing African mango seed extract,
      citrus fruits extract, Coleus forskohlii root extract, dihydrocapsiate and red
      pepper fruit extract reduced body weight and fat gain in response to high-fat
      diet without impairing muscle mass.The novel blend stimulated thermogenesis as
      shown by the increased thermal imaging and UCP1 protein expression in brown
      adipose tissue, indicating that improvement in body composition potentially
      occurred due to a fat-burning effect.The positive effects on body weight, fat,
      and thermogenesis were improved when the novel blend was administered in
      combination with a whey protein supplement suggesting that protein provides a
      synergistic fat-burning effect. Abbreviations Used: BAT: Brown adipose tissue,
      UCP1: Uncoupling protein 1, DEXA: Dual-energy X-ray absorptiometry.

PMID- 29568186
TI  - In vitro Evaluation of Antioxidant Potential of Isolated Compounds and Various
      Extracts of Peel of Punica granatum L.
AB  - Background: Punica granatum L. (Lythraceae) peel has been proven to exhibit
      widespread pharmacological application against multitude of diseases due to the
      presence of bioactive principles. Objective: The objective is to isolate the
      bioactive compounds from the pericarp of P. granatum and to evaluate the
      antioxidant activity of various extracts. Materials and Methods: Dried peel of P.
      granatum was extracted with aqueous acetone and chromatographed on Diaion HP-20.
      Enriched fractions were rechromatographed on Sephadex LH-20 and purified on
      preparative high-performance liquid chromatography to identify individual
      compounds. The dried peel was extracted with different solvents to evaluate the
      antioxidant activity of the extracts. Results: On the chemical investigation,
      three compounds were isolated and characterized as punicalagin, 2,3-(S)
      hexahydroxydiphenoyl-D-glucose, and punicalin, using various spectroscopic
      techniques. Conclusion: Results indicate that the isolated compounds have
      possessed antioxidant activity, and aqueous, methanol, and aqueous acetone
      extract showed significant scavenging of 2,2-diphenyl-1-picrylhydrazyl and 2,2'
      azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radicals. SUMMARY: In vitro
      antioxidant activity of Punica granatum extracts was evaluated by 2,2-diphenyl-1
      picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)
      assayDried peel of P. granatum was extracted with different solvents to evaluate
      the antioxidant activity of the extractsAqueous acetone extract was found to be
      most active and chromatographed further to afford punicalagin, 2,3-(S)
      hexahydroxydiphenoyl-D-glucose, and punicalinThe presence of antioxidant
      properties of three compounds in the peel of P. granatum has been demonstrated.
      Abbreviations Used: HPLC: High-performance liquid chromatography; HHDP:
      Hexahydroxydiphenoyl; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2'-azino-bis
      (3-ethylbenzthiazoline-6-sulfonic acid); UV: Ultraviolet; PDA: Photodiode array;
      LC: Liquid chromatography; NMR: Nuclear magnetic resonance; MHz: Megahertz; w/v:
      Weight by volume; MS: Mass spectra.

PMID- 29568187
TI  - Anticonvulsant and Antioxidant Effects of Musa sapientum Stem Extract on Acute
      and Chronic Experimental Models of Epilepsy.
AB  - Background: Musa sapientum (banana) plant extract has been shown to possess
      antioxidant activity in previous studies. Neuronal injury resulting from
      oxidative stress is an important factor involved in pathogenesis of epilepsy.
      Objective: The present study aimed to evaluate the anticonvulsant activity of M.
      sapientum stem extract (MSSE) in acute and chronic experimental models in mice
      and its effects on various markers of oxidative stress in the brain of
      pentylenetetrazole (PTZ)-kindled animals. Material and Methods: Maximal
      electroshock seizures (MES) and PTZ-induced convulsion models were used for acute
      studies. For the chronic study, the effect of MSSE on the development of kindling
      was studied. For the evaluation of the effects of MSSE on oxidative stress in
      brain, malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated
      in the brains of the kindled animals. Results: MSSE significantly increased the
      latency to onset of myoclonic jerks and the duration of clonic convulsions
      following PTZ administration. The MSSE pretreated group showed significantly
      reduced mean seizure score on PTZ-induced kindling. There was a significant
      increase in the brain MDA levels and decrease in GSH levels in response to PTZ
      induced kindling. On MSSE pretreatment, there was a significant decrease in the
      MDA levels in the brains, though the increase in the GSH levels was not
      significant. Conclusion: The results from this study suggest the presence of
      significant anticonvulsant activity in MSSE, in both acute and chronic PTZ
      induced seizure models, which could be due to its antioxidant activity, as is
      reflected by the change in oxidative stress markers in brain. SUMMARY: Evaluation
      of the anticonvulsant activity of Musa sapientum and its effects on various
      markers of oxidative stress in the brain has not been done previously to the best
      of our knowledgeM. sapientum stem extract (MSSE) significantly increased the
      latency to onset of myoclonic jerks and the duration of clonic convulsions in the
      experimental modelsThe MSSE pretreated group showed significantly reduced mean
      seizure score on pentylenetetrazole (PTZ)-induced kindlingThere was significant
      increase in the brain malondialdehyde (MDA) levels and decrease in glutathione
      (GSH) levels in response to PTZ-induced kindlingOn MSSE pretreatment, there was a
      significant decrease in the MDA levels in the brain, though the increase in the
      GSH levels was not significant. Abbreviations Used: MSSE: Musa sapientum stem
      extract, PTZ: Pentylenetetrazole, MES: Maximal electroshock seizures, MDA:
      Malondialdehyde, GSH: Glutathione, SOD: Superoxide dismutase, THLE: Tonic
      hindlimb extension.

PMID- 29568188
TI  - Antiproliferative and Apoptotic Activities of the Medicinal Plant Ziziphus
      obtusifolia.
AB  - Background: Ziziphus obtusifolia is a spiny shrub found in Northwest Mexico
      desert, with traditional medicinal use to treat several diseases including
      cancer. Objective: The aims of the present study were to evaluate the
      antiproliferative and apoptotic activities of the aerial parts of this plant.
      Materials and Methods: The methanol extract and its fractions were prepared using
      several solvents. The antiproliferative activity was evaluated by the (3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) (MTT) assay on HeLa, A549, RAW
      264.7, M12.C3.F6, and L-929 cell lines, and the apoptotic activity using Annexin
      V and (5,50,6,60-tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine
      iodide) staining. The most active fraction was further separated by column
      chromatography. Results: The most active fraction was hexane with an IC50 of 90.4
      MUg/mL against RAW 264.7, 94 MUg/mL against M12.C3.F6, 165.5 MUg/mL against HeLa
      and 187.7 MUg/mL against A549 cell lines. In apoptotic activity assays the
      methanol extract and its n-hexane fraction were found to induce mitochondrial
      depolarization in HeLa cells (83 and 87% respectively), and both induced the
      externalization of the phosphatidylserine increasing the percentage of cells in
      early apoptosis from 1.4% in untreated control cells, to 1.9% and 3.5% for
      methanol extract and n-hexane fraction-treated cells, respectively, statistically
      different for the total percentage of apoptotic cells (P < 0.05). Conclusions:
      These results show that Z. obtusifolia has antiproliferative and apoptotic
      activities in vitro and confirms its use in traditional medicine. SUMMARY: The
      methanol extract and its fractions using several solvents were evaluated in the
      antiproliferative activity by the MTT assay on HeLa, A549, RAW 264.7, M12.C3.F6,
      and L-929 cell lines, and the apoptotic activity using Annexin V and (5,50,6,60
      tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide) staining. The
      most active fraction against cell lines was hexane. In apoptotic activity assays,
      the methanol extract and its n-hexane fraction were found to induce mitochondrial
      depolarization. This results we showed that Ziziphus obtusifolia has
      antiproliferative and apoptotic activities in vitro.Abbreviations Used: DMEM:
      Dulbecco's modified eagle's medium, DMSO: Dimethyl sulfoxide, MTT: (3-4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium), JC-1: (5,50,6,60-tetra-chloro
      1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide), FBS: Fetal bovine serum,
      CAPE: Caffeic acid phenethyl ester, PBS: Phosphate-buffered saline.

PMID- 29568189
TI  - Isolation of 5,7-Dihydroxy, 6,8-Dimethyl Flavanone from Syzygium aqueum with Its
      Antioxidant and Xanthine Oxidase Inhibitor Activities.
AB  - Background: Syzygium aqueum Burm.f. Alston (water apple) belonging to Myrtaceae
      family was originated from tropical areas. It was traditionally used as a
      medicinal plant. Objective: The objective of the study was to isolate the active
      compound from the methanolic extract of S. aqueum leaves. Methods: Extraction was
      done using continuous extraction with methanol as a solvent. The extract was then
      fractionated using liquid-liquid extraction, vacuum liquid chromatography, and
      radial chromatography. Recrystallization was done for purification. The structure
      of the compound was determined by Ultraviolet-Visible and (1D and 2D) nuclear
      magnetic resonance (NMR) spectrometer. Results: The isolate showed maximum
      wavelengths at 347 (band I) and 296 (band II) nm. After addition of NaOH and CH3
      COONa, the maximum wavelengths of band II moved to 340 and 339 nm, respectively.
      There was no change in wavelengths after addition CH3 COONa/H3 BO3 and AlCl3. The
      1H-NMR spectrum showed 16 protons, whereas 13C-NMR spectrum showed 15 carbons.
      Based on those data, the isolate was determined as 5,7-dihydroxy-6,8-dimethyl
      flavanone (demethoxymatteucinol). At a concentration of 100 and 50 MUg/mL, it
      could inhibit 25.13% of xanthine oxidase (XO) activity and scavenge 11.87% of
      diphenyl-picrylhydrazyl, respectively. Conclusion: Demethoxymatteucinol was
      isolated for the first time from S. aqueum and it had mild antioxidant and XO
      inhibitory activities. SUMMARY: One flavonoid compound, which 5,7-dihydroxy 6,8
      dimethyl flavanone (demethoxymatteucinol), was isolated from the methanol extract
      of Syzygium aqueum. It had mild antioxidant and xanthine oxidase inhibitory
      activities. Abbreviations Used: CH3 COONa/H3 BO3: Natrium acetate/Boric acid;
      DPPH: Diphenyl-picrylhydrazyl, NMR: Nuclear Magnetic Resonance; ABTS: 2,2'
      azinobis (3-ethyl-benzothiazline-6-sulfonic acid); AEAC: Ascorbic Acid Equivalent
      Antioxidant Capacity; UV-Vis: Ultraviolet-Visible; XO: Xanthine Oxidase; HSQC:
      Heteronuclear Single Quantum Coherence; HMBC: (Heteronuclear Multiple Bond
      Correlation).

PMID- 29568190
TI  - The Protective Effect of Different Extracts of Three Artemisia Species against
      H2O2-Induced Oxidative Stress and Apoptosis in PC12 Neuronal Cells.
AB  - Background: Oxidative stress causes cell damage and is involved in many
      neurological diseases. The antioxidant properties of plant materials for the
      maintenance of health and protecting against different diseases stimulated
      scientist to investigate different herbs. Different Artemisia species have
      exhibited antioxidant activity. This study aims to investigate whether different
      Artemisia species could protect the PC12 cells against oxidative stress mediated
      by H2O2. Methods: For this purpose, different extracts of three Artemisia species
      (Artemisia aucheri, Artemisia turanica, and Artemisia turcomanica) were prepared
      using petroleum ether, dichloromethane, ethyl acetate, ethanol, and Water:
      Ethanol mixture (1:1 volume ratio). The protective effect of the prepared
      extracts against H2O2-induced cytotoxicity and reactive oxygen species production
      were compared. The effect of treatment of PC12 cells with different extracts on
      total glutathione (GSH) level, caspase-3 activity, and mitochondrial membrane
      potential were also compared. Results: The A. aucheri extracts could not rescue
      the PC12 cells from oxidative stress consequences. The A. turanica and A.
      turcomanica extracts were found potent in suppressing the toxicity and apoptosis
      of PC12 cells mediated by H2O2 and significantly antagonized the H2O2-induced GSH
      depletion. The hydroethanolic and ethyl acetate extracts of A. turanica and the
      petroleum ether and hydroethanolic extracts of A. turcomanica more efficiently
      suppressed cytotoxicity and loss of GSH caused by H2O2. Conclusion: This study
      shows the protective effects of Artemisia extracts on PC12 cell line and
      suggested that these species could be also considered as promising
      neuroprotective agents in treatment of different neurodegenerative diseases.
      SUMMARY: Artemisia turanica and Artemisia turcomanica extracts were found to
      potentially exert neuroprotective effect on PC12 cells. The results exhibited
      that the cytoprotective potential and anti-apoptotic mechanism of these species
      is not the same for different extracts, and suggested that based on the type of
      species and the type of solvents used in extraction, both intrinsic and extrinsic
      pathways could be included in the anti-apoptotic mechanism of these species.
      Abbreviations Used: GSH: Glutathion. ROS: Reactive Oxygen Species. GSSG:
      Glutathione disulfide. DCF-DA:2',7'-Dichlorofluorescin diacetate. FBS: Fetal
      Bovin Serum. MMP: Mitochondrial Membrane Potential. H-Et: Hydro-ethanolic. DCM:
      Dichloromethane. PE: Petroleum Ether. Et: Etanolic. EA: Ethyl Acetate.

PMID- 29568191
TI  - Identification of Antidiabetic Compounds from Polyphenolic-rich Fractions of
      Bulbine abyssinica A. Rich Leaves.
AB  - Background: Bulbine abyssinica has been reported to possess a variety of
      pharmacological activities traditionally. Previous work suggested its
      antidiabetic properties, but information on the antidiabetic compounds is still
      lacking. Objective: The present research exertion was aimed to isolate and
      identify biologically active polyphenols from B. abyssinica leaves and to
      evaluate their efficacy on carbohydrate digesting enzymes. Materials and Methods:
      Fractionation of the polyphenolic contents from the methanolic extract of B.
      abyssinica leaves was executed by the silica gel column chromatography to yield
      different fractions. The antioxidant activities of these fractions were carried
      out against 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium
      salt (ABTS), 2,2-diphenyl-1-picrylhydrazyl radicals, and ferric ion-reducing
      antioxidant power (FRAP). In vitro antidiabetic experimentation was performed by
      evaluating the alpha-amylase and alpha-glucosidase inhibitory capacity. The
      isolated polyphenols were then identified using liquid chromatography and mass
      spectroscopy (LC/MS). Results: Out of the eight polyphenolic fractions (BAL 1-8),
      BAL-4 has the highest inhibitory activity against ABTS radicals whereas BAL-6
      showed potent ferric ion-reducing capacity. BAL-5 was the most effective fraction
      with antidiabetic activity with IC50of 140.0 and 68.58 +/- 3.2 MUg/ml for alpha
      amylase and alpha-glucosidase inhibitory activities, respectively. All the
      fractions competitively inhibited alpha-amylase, BAL-5 and BAL-6 also inhibited
      alpha-glucosidase competitively, while BAL-4 and BAL-1 exhibited noncompetitive
      and near competitive inhibitions against alpha-glucosidase, respectively. The
      LC/MS analysis revealed the presence of carvone in all the fractions.
      Conclusions: The present study demonstrates the antioxidant and antidiabetic
      activities of the isolated polyphenols from B. abyssinica. SUMMARY: Polyphenols
      were successfully isolated and identified from Bulbine abyssinica leavesThe
      isolated polyphenols are biologically active with high antioxidant as well as
      inhibitor of carbohydrate-digesting enzymesB. abyssinica can be a good source of
      amylase and glucosidase inhibitorsB. abyssinica can be used as complementary or
      alternative therapeutic agents especially for the treatment of diabetesCarvone,
      quercetin, and psoralen could be the compounds responsible for the alpha-amylase
      and alpha-glucosidase inhibitory activities. Abbreviations Used: ABTS: 2,2'-Azino
      bis (3-ethylbenzthiazoline-6-sulfonic acid), DPPH: 2,2-diphenyl-1-picrylhydrazyl,
      FRAP: Ferric ion-reducing antioxidant power, LC/MS: Liquid chromatography and
      mass spectroscopy, AGEs: Advanced glycation end products, TLC: Thin-layer
      chromatography, MeOH: Methanol, PNP-G: rho-Nitrophenyl-alpha-D-Glucoside, R2:
      Coefficient of determination, mgQE: Milligram quercetin equivalent, mgTAE:
      Milligram tannic acid equivalent, mgCE: Milligram catechin equivalent, g: Gram.

PMID- 29568192
TI  - Antioxidant, Anti-inflammatory, Analgesic Properties, and Phytochemical
      Characterization of Stem Bark Extract and Fractions of Anthocleista nobilis.
AB  - Background: Anthocleista nobilis (Loganiaceae) is used by Mbano people of Imo
      State, Nigeria, for the treatment of various ailments. Objective: The aim of this
      study is to evaluate the antioxidant, anti-inflammatory, and analgesic properties
      of the methanol extract, fractions, and subfractions of A. nobilis. Materials and
      Methods: The powdered stem bark was extracted with methanol and sequentially
      fractionated into n-hexane, ethyl acetate, and butanol fractions. The
      constituents of the fractions were analyzed using high-pressure liquid
      chromatography (HPLC), and the components were identified by dereplication.
      Antioxidant potential of the extracts and fractions was investigated using 2,2
      diphenyl-1-picrylhydrazyl free-radical scavenging method. Anti-inflammatory and
      analgesic activities of the extract and fractions were also investigated using
      xylene-induced inflammation and acetic acid-induced writhing models,
      respectively. Results: A total of five compounds isovitexin (Rt = 18.77 min),
      isovitexin-2''-O-xyl (Rt = 19.68 min), p-Hydroxybenzoic acid (Rt = 11.88 min),
      Sarasinoside L (Rt = 19.64 min), isovitexin (Rt = 18.77), and apigenin
      monoglycoside (Rt = 19.64 min) were identified by HPLC analysis and
      dereplication. The ethyl acetate fraction and subfraction elicited the best anti
      inflammatory activity. The ethyl acetate subfraction also inhibited acetic acid
      induced pain by 79% and 85.0% at the doses of 100 mg/kg and 200 mg/kg,
      respectively, which was better than 71.1% and 81.3% observed for diclofenac at
      similar doses. Conclusion: A. nobilis could be a potential source of anti
      inflammatory and analgesic lead compounds. SUMMARY: The extract, fractions and
      subfractions of Anthocleista nobilis were screened or antioxidant, anti
      inflammatory and Analgesic properties in vitro and in mice models. Some of the
      components were identified by dereplication after HPLC analysis. The results
      demonstrated potent anti-inflammatory and analgesic property of the extracts and
      fractions. The dereplication analysis also identified vitexin and related
      compounds. Abbreviation used: HPLC: High performance Liquid Chromatography; VLC:
      Vacuum Liquid Chromatography; DPPH: 2,2-Diphenyl-1-pycrylhydrazine; SPSS:
      Statistical Package for the Social Sciences; ROS: Reactive Oxygen Species.

PMID- 29568193
TI  - Method Development and Validation for the Determination of Caffeine: An Alkaloid
      from Coffea arabica by High-performance Liquid Chromatography Method.
AB  - Objective: The present study was investigated to develop and validate a reversed
      phase high performance liquid chromatography method for the determination of
      caffeine from bean material of Coffee arabica. Materials and Methods: The
      separation was achieved on a reversed-phase C18 column using a mobile phase
      composed of water: methanol (50:50) at a flow rate of 1.0 mlmin-1. The detection
      was carried out on a UV detector at 272 nm. The developed method was validated
      according to the requirements for International Conference on Harmonisation (ICH)
      guidelines, which includes specificity, linearity, precision, accuracy, limit of
      detection and limit of quantitation. Results: The developed method validates good
      linearity with excellent correlation coefficient (R2 > 0.999). In repeatability
      and intermediate precision, the percentage relative standard deviation (% RSD) of
      peak area was less than 1% shows high precision of the method. The recovery rate
      for caffeine was within 98.78% - 101.28% indicates high accuracy of the method.
      The low limit of detection and limit of quantitation of caffeine enable the
      detection and quantitation of caffeine from C. arabica at low concentrations.
      Conclusion: The developed HPLC method is a simple, rapid, precisely, accurately
      and widely accepted and it is recommended for efficient assays in routine work.
      SUMMARY: A simple, accurate, and sensitive high-performance liquid chromatography
      (HPLC) method for caffeine from Coffea arabica has been developed and validated.
      The developed HPLC method was validated for linearity, specificity, precision,
      recovery, limits of detection, and limits of quantification by the International
      Conference on Harmonization guidelines. The results revealed that the proposed
      method is highly reliable. This method could be successfully applied for routine
      quality work analysis.Abbreviation Used:C. arabica: Coffee arabica, ICH:
      International Conference on Harmonisation, % RSD: Percentage Relative Standard
      Deviation, R2: Correlation Coefficient, ppm: Parts per million, LOD: Limits of
      detection, LOQ: Limits of quantification, SD: Standard deviation, S: Slope, RP
      HPLC: Reverse phase high performance liquid chromatography, v/v: Volume per
      volume.

PMID- 29568194
TI  - Analytical Method Development and Validation for the Simultaneous Estimation of
      Abacavir and Lamivudine by Reversed-phase High-performance Liquid Chromatography
      in Bulk and Tablet Dosage Forms.
AB  - Objective: A simple rapid, accurate, precise, and reproducible validated reverse
      phase high performance liquid chromatography (HPLC) method was developed for the
      determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage
      forms. Methods: The quantification was carried out using Symmetry Premsil C18
      (250 mm * 4.6 mm, 5 MUm) column run in isocratic way using mobile phase
      comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a
      detection wavelength of 245 nm and injection volume of 20 MUl, with a flow rate
      of 1 ml/min. Results: In the developed method, the retention times of ABAC and
      LAMI were found to be 3.5 min and 7.4 min, respectively. The method was validated
      in terms of linearity, precision, accuracy, limits of detection, limits of
      quantitation, and robustness in accordance with the International Conference on
      Harmonization guidelines. Conclusion: The assay of the proposed method was found
      to be 99% - 101%. The recovery studies were also carried out and mean % recovery
      was found to be 99% - 101%. The % relative standard deviation from
      reproducibility was found to be <2%. The proposed method was statistically
      evaluated and can be applied for routine quality control analysis of ABAC and
      LAMI in bulk and in tablet dosage form. SUMMARY: Attempts were made to develop RP
      HPLC method for simultaneous estimation of Abacavir and Lamivudine for the RP
      HPLC method. The developed method was validated according to the ICH guidelines.
      The linearity, precision, range, robustness were within the limits as specified
      by the ICH guidelines. Hence the method was found to be simple, accurate,
      precise, economic and reproducible. So the proposed methods can be used for the
      routine quality control analysis of Abacavir and Lamivudine in bulk drug as well
      as in formulations. Abbreviations Used: HPLC: High-performance liquid
      chromatography, UV: Ultraviolet, ICH: International Conference on Harmonization,
      ABAC: Abacavir, LAMI: Lamivudine, HIV: Human immunodeficiency virus, AIDS:
      Acquired immunodeficiency syndrome, NRTI: Nucleoside reverse transcriptase
      inhibitors, ARV: Antiretroviral, RSD: Relative standard deviation, RT: Retention
      time, SD: Standard deviation.

PMID- 29568195
TI  - Evaluation of Antithrombotic Activities of Solanum xanthocarpum and Tinospora
      cordifolia.
AB  - Background: Solanum xanthocarpum and Tinospora cordifolia have been reported to
      exhibit anti-inflammatory, antiarthritic, antioxidant, antiallergic, and
      hepatoprotective activities. The origins of many of the currently available
      antithrombotic treatments are from natural products and natural sources.
      Objective: To investigate the antithrombotic activities of methanolic leaf
      extracts of S. xanthocarpum(SXME) and T. cordifolia(TCME). Materials and Methods:
      Antithrombotic activities were assessed by thrombin inhibition assay, thrombin
      generation assay, platelet adhesion assay on collagen-coated surface, and
      platelet PAC1-FITC binding by flow cytometry. Results: SXME significantly
      inhibited thrombin activity at 5-20 mg/ml concentrations, whereas TCME inhibited
      thrombin activity at 500 MUg/ml-5 mg/ml concentrations. Further, SXME inhibited
      thrombin generation at 2-20 mg/ml concentrations, whereas TCME exhibited
      significant inhibition at 200 MUg/ml, suggesting that TCME has higher efficacy as
      compared to SXME. Moreover, SXME did not inhibit platelet adhesion on collagen
      coated surface, whereas TCME inhibited platelet adhesion on collagen-coated
      surface at 5 mg/ml. Indomethacin showed significant inhibition in platelet
      adhesion at 300 MUM. Further, SXME inhibited thrombin-induced platelet activation
      (PAC1-FITC binding) significantly at 1 mg/ml by about 80%, whereas TCME inhibited
      thrombin-induced platelet activation (PAC1-FITC binding) by about 40% at 1 mg/ml.
      Conclusion: These results strongly suggested that SXME and TCME possess
      antithrombotic activities. However, further studies are essential to find out the
      active constituent responsible for antithrombotic effect. SUMMARY: The methanolic
      extracts obtained from the leaves of Tinospora cordifolia and Solanum
      xanthocarpum were evaluated for antithrombotic activity by thrombin inhibition
      assay, thrombin generation assay, platelet adhesion assay and platelet activation
      assay by flow cytometry. These extracts inhibited thrombin activity and thrombin
      generation in rat plasma. Also, these extracts inhibited thrombin induced
      platelet activation in PAC1-FITC binding study in flow cytometry. Abbreviation
      Used: DVT: Deep vein thrombosis, TCME: Tinospora cordifolia methanolic extract,
      SXME: Solanum xanthocarpum methanolic extract, IL-1beta: interleukin-1beta, DMSO:
      dimethyl sulfoxide, PRP: Platelet rich plasma.

PMID- 29568196
TI  - Anti-inflammatory Effect of an Extract of Agave americana on Experimental
      Animals.
AB  - Background: Medicinal plants have the potential treasure to treat medical
      conditions for a long time based on error and trial method. Agave americana has
      been known as century plant or American aloe. The leaves contain genins,
      saponins, steroidal flavonoids, isoflavones, and coumarins. It has long been used
      for anti-inflammatory effects. Objectives: This study was designed to evaluate
      the anti-inflammatory activity of the extract of A. americana. Materials and
      Methods: A. americana leaves extract is collected and the extract is done by
      percolation method. Inflammation is induced in experimental animals' carrageenan
      induced paw edema model and cotton pellet-induced granuloma model. The extract of
      A. americana and standard, aspirin and indomethacin are given orally for the anti
      inflammatory effects. The anti-inflammatory effects were measured at regular
      intervals of time to see the percentage inhibition of paw edema and reduction of
      weight of granuloma with percentage protection to compare the effect of the
      extract with the control and standard. Results: The extract of A. americana
      showed improved in percentage inhibition of paw edema in graded doses of
      hydroalcoholic extract of A. americana (HEAA) as compared with control in
      carrageenan-induced paw edema model. The percentage inhibition of 400 mg/kg of
      HEAA at the 3rd h is almost comparable with the standard, aspirin. On the other
      hand, graded doses (200 and 400 mg/kg) showed a highly significant reduction (P <
      0.001) in the weights of granuloma in comparison with the control in cotton
      pellet-induced granuloma model. The percentage inhibition of weight of granuloma
      by 400 mg/kg of HEAA is quite comparable to the standard, Indomethacin.
      Conclusion: Anti-inflammatory activity is seen with the graded dose of HEAA. The
      plant contains flavonoids and genins which have been shown to have anti-edematous
      effects in the acute phase of inflammation. Thus, the plant contributes to its
      anti-inflammatory activity. Thus, higher doses of A. americana leaves need to be
      used to have the better understanding of the mechanism of anti-inflammation.
      SUMMARY: The hydroalcoholic extract from Agave americana (100, 200, and 400
      mg/kg, HEAA) were studied in carrageenan-induced paw edema model and cotton
      pellet-induced granuloma model in Wistar rats. The plant contains flavonoids and
      genins which have been shown to have anti-edematous effects in the acute phase of
      inflammation. The results were good with the higher doses of 200 and 400 mg/kg of
      HEAA. Its in vivo anti-inflammatory activity is in good agreement with the
      traditional use of A. americana. Abbreviation Used: HEAA: Hydroalcoholic extract
      of Agave americana leaves; SEM: Standard error mean; ANOVA: Analysis of variance;
      n: Number; g: gram; w/w: weight by weight; h: hour; kg: kilogram; mg: milligram.

PMID- 29568197
TI  - Assessment of In vivo Antiviral Potential of Datura metel Linn. Extracts against
      Rabies Virus.
AB  - Objective: The soxhlet, cold, and ayurvedic extracts of Datura metel Linn. were
      evaluated for in vivo antirabies activity. Materials and Methods: Soxhlet and
      cold extraction method were used to extract Datura (fruit and seed) extracts, and
      ayurvedic extraction of Datura was prepared. In vivo toxicity assay was performed
      as per the OECD 420. LD50 dose was calculated by Reed and Muench method. The in
      vivo antirabies activity was screened in Swiss albino mice with the virus
      challenge dose of 10 LD50 (intracerebrally) in both preexposure (PE) and
      postexposure treatment with oral administration of Datura extracts in Swiss
      albino mice and observed for 21 days. The virus load in the mice brain was
      evaluated by TCID50 titration method. Results: Datura (ayurvedic preparation) was
      found to be nontoxic up to 2000 mg/kg in Swiss albino mice, i.e., 60 mg/30 g of
      mice, when administered (0.5 ml) orally and observed till 21 days. Up to 20%
      survival rate on the test group (PE of Datura extracts) up to 14 days
      postinfection as compared to the virus control group (10 LD50) was observed. No
      survival rate was observed in the postexposure group of Datura extract; however,
      the survival time was increased by 4 days as compared to the virus control group.
      Viral load of the infected mice brain sample was estimated in vero cell line, and
      3 log reduction in the virus titer was observed in text group as compared to the
      virus control, suggesting that Datura extract has an in vivo antirabies activity.
      Conclusion: To the best of our knowledge, this is the first study of in vivo
      antiviral activity of an ayurvedic preparation of D. metel Linn. against rabies
      virus. Datura extracts have a potential in vivo antirabies activity. SUMMARY: In
      the present study, Datura metel Linn. (ayurvedic preparation) extract exhibited
      survival (20%) in the preexposure (PE) of the virus and the survival time was
      increased in the postexposure treatment where the disease was established. The
      mortality was observed, and the viral load was determined by titration method.
      Abbreviation Used: TCID50: tissue culture infectious dose 50; LD50: lethal dose
      50; RV CVS: Rabies virus challenge virus standard; PE: Pre exposure; IC:
      intracerebral; PI: post infection; FITC: Fluorescein isothiocyanate.

PMID- 29568198
TI  - Comparative Molluscicidal and Schistosomicidal Potentiality of Two Solanum
      Species and Its Isolated Glycoalkaloids.
AB  - : Schistosomiasis is the most noteworthy parasitic disease after malaria.
      Furthermore, the significant activity of the genus Solanum against Schistosoma
      worms and its intermediate host snails reinforced the study of Solanum
      seaforthianum Andr. (SS) and Solanum macrocarpon L. (SM) for their molluscicidal
      and schistosomicidal potentiality. In this study, different extracts, fractions
      and isolated compounds of both Solanum species are evaluated for the
      molluscicidal and schistosomicidal potentialities. The niclosamide was used as
      positive molluscicide control against Biomphalaria alexandrina snails. Different
      extracts, fractions, or isolated compounds were used at a concentration of 100
      MUg/ml and dead snails were counted in each case. On the other hand, washed and
      sterilized Schistosoma mansoni adult worms were used in three replicates, and
      three worm pairs were placed in each well with 2 ml test solution of 100 MUg/ml
      concentration. Positive (praziquantel [PZQ] 0.2 ug/ml) and negative controls were
      concurrently used and examined daily for 3 days for viability. The mortality rate
      was calculated and then both LC50 and LC90 were determined in triplicates.
      Highest potency was indicated to total glycoalkaloid (TGA) fraction of SM
      followed by TGA of SS. On the other hand, TGA fractions of both species showed
      higher potency than other extracts and isolated compounds. Meanwhile, solasodine
      free aglycone showed declined activity compared to its glycosides. Promising
      molluscicidal and schistosomicidal activities were displayed which are attributed
      to the glycoalkaloid content. Therefore, this study can efficiently contribute
      toward validation of the traditional use of SS and SM in schistosomiasis control.
      SUMMARY: The current study evaluated the molluscicidal and schistosomicidal
      activities of different extracts and fractions of two Solanum species. The
      glycoalkaloids content depicted a promising activity against both the snails and
      the adult worms. Abbreviations Used: PZQ; Praziquantel, SM; Solanum macrocarpon,
      SS; Solanum seaforthianum, TGA; total glycoalkaloid.

PMID- 29568200
TI  - NOD2- and disease-specific gene expression profiles of peripheral blood
      mononuclear cells from Crohn's disease patients.
AB  - AIM: To investigate disease-specific gene expression profiles of peripheral blood
      mononuclear cells (PBMCs) from Crohn's disease (CD) patients in clinical
      remission. METHODS: Patients with CD in clinical remission or with very low
      disease activity according to the Crohn's disease activity index were genotyped
      regarding nucleotide-binding oligomerization domain 2 (NOD2), and PBMCs from wild
      type (WT)-NOD2 patients, patients with homozygous or heterozygous NOD2 mutations
      and healthy donors were isolated for further analysis. The cells were cultured
      with vitamin D, peptidoglycan (PGN) and lipopolysaccharide (LPS) for defined
      periods of time before RNA was isolated and subjected to microarray analysis
      using Clariom S assays and quantitative real-time PCR. NOD2- and disease-specific
      gene expression profiles were evaluated with repeated measure ANOVA by a general
      linear model. RESULTS: Employing microarray assays, a total of 267 genes were
      identified that were significantly up- or downregulated in PBMCs of WT-NOD2
      patients, compared to healthy donors after challenge with vitamin D and/or a
      combination of LPS and PGN (P < 0.05; threshold: >= 2-fold change). For further
      analysis by real-time PCR, genes with known impact on inflammation and immunity
      were selected that fulfilled predefined expression criteria. In a larger cohort
      of patients and controls, a disease-associated expression pattern, with higher
      transcript levels in vitamin D-treated PBMCs from patients, was observed for
      three of these genes, CLEC5A (P < 0.030), lysozyme (LYZ; P < 0.047) and TREM1 (P
      < 0.023). Six genes were found to be expressed in a NOD2-dependent manner (CD101,
      P < 0.002; CLEC5A, P < 0.020; CXCL5, P < 0.009; IL-24, P < 0.044; ITGB2, P <
      0.041; LYZ, P < 0.042). Interestingly, the highest transcript levels were
      observed in patients with heterozygous NOD2 mutations. CONCLUSION: Our data
      identify CLEC5A and LYZ as CD- and NOD2-associated genes of PBMCs and encourage
      further studies on their pathomechanistic roles.

PMID- 29568199
TI  - Functional macrophages and gastrointestinal disorders.
AB  - Macrophages (MPhi) differentiate from blood monocytes and participate in innate
      and adaptive immunity. Because of their abilities to recognize pathogens and
      activate bactericidal activities, MPhi are always discovered at the site of
      immune defense. MPhi in the intestine are unique, such that in the healthy
      intestine, they possess complex mechanisms to protect the gut from inflammation.
      In these complex mechanisms, they produce anti-inflammatory cytokines, such as
      interleukin-10 and transforming growth factor-beta, and inhibit the inflammatory
      pathways mediated by Toll-like receptors. It has been demonstrated that resident
      MPhi play a crucial role in maintaining intestinal homeostasis, and they can be
      recognized by their unique markers. Nonetheless, in the inflamed intestine, the
      function of MPhi will change because of environmental variation, which may be one
      of the mechanisms of inflammatory bowel disease (IBD). We provide further
      explanation about these mechanisms in our review. In addition, we review recent
      discoveries that MPhi may be involved in the development of gastrointestinal
      tumors. We will highlight the possible therapeutic targets for the management of
      IBD and gastrointestinal tumors, and we also discuss why more details are needed
      to fully understand all other effects of intestinal MPhi.

PMID- 29568201
TI  - Three-microRNA signature identified by bioinformatics analysis predicts prognosis
      of gastric cancer patients.
AB  - AIM: To identify multiple microRNAs (miRNAs) for predicting the prognosis of
      gastric cancer (GC) patients by bioinformatics analysis. METHODS: The original
      microarray dataset GSE93415, which included 20 GC and 20 tumor adjacent normal
      gastric mucosal tissues, was downloaded from the Gene Expression Omnibus database
      and used for screening differentially expressed miRNAs (DEMs). The cut-off
      criteria were P < 0.05 and fold change > 2.0. In addition, we acquired the miRNA
      expression profiles and clinical information of 361 GC patients from The Cancer
      Genome Atlas database to assess the prognostic role of the DEMs. The target genes
      of miRNAs were predicted using TargetScan, miRDB, miRWalk, and DIANA, and then
      the common target genes were selected for functional enrichment analysis.
      RESULTS: A total of 110 DEMs including 19 up-regulated and 91 down-regulated
      miRNAs were identified between 20 pairs of GC and tumor adjacent normal tissues,
      and the Kaplan-Meier survival analysis found that a three-miRNA signature (miR
      145-3p, miR-125b-5p, and miR-99a-5p) had an obvious correlation with the survival
      of GC patients. Furthermore, univariate and multivariate Cox regression analyses
      indicated that the three-miRNA signature could be a significant prognostic marker
      in GC patients. The common target genes of the three miRNAs are added up to 108
      and used for Gene Functional Enrichment analysis. Biological Process and
      Molecular Function analyses showed that the target genes are involved in cell
      recognition, gene silencing and nucleic acid binding, transcription factor
      activity, and transmembrane receptor activity. Cellular Component analysis
      revealed that the genes are portion of nucleus, chromatin silencing complex, and
      TORC1/2 complex. Biological Pathway analysis indicated that the genes participate
      in several cancer-related pathways, such as the focal adhesion, PI3K, and mTOR
      signaling pathways. CONCLUSION: This study justified that a three-miRNA signature
      could play a role in predicting the survival of GC patients.

PMID- 29568202
TI  - Differing profiles of people diagnosed with acute and chronic hepatitis B virus
      infection in British Columbia, Canada.
AB  - AIM: To describe the characteristics of people diagnosed with acute and chronic
      hepatitis B virus (HBV) infection in British Columbia (BC). METHODS: We used data
      from the BC Hepatitis Testers Cohort (BC-HTC), which includes all individuals
      tested for hepatitis C virus (HCV) or human immunodeficiency virus (HIV) or those
      diagnosed with HBV or active tuberculosis in BC since 1990. These data were
      integrated with prescription drug, medical visit, hospitalization and mortality
      data. HBV cases were classified as acute or chronic according to provincial
      guidelines. We compared characteristics of individuals by HBV infection group
      (acute, chronic and negative). Factors associated with acute or chronic HBV
      infection were assessed with multinomial logistic regression models in comparison
      to the HBV negative group. RESULTS: 46498 of the 1058056 eligible BC-HTC
      participants were diagnosed with HBV infection. 4.3% of HBV positive individuals
      were diagnosed with acute HBV infections while 95.7% had chronic infections.
      Problematic alcohol use, injection drug use, and HIV or HCV co-infection were
      more common among individuals diagnosed with acute HBV compared to those with
      chronic infections and HBV negative individuals. In multivariable multinomial
      logistic regression models, we observed significant associations between acute or
      chronic HBV diagnosis and being male, age at HBV diagnosis or birth cohort, South
      and East Asian ethnicity, HCV or HIV infection, and injection drug use. The odds
      of acute HBV decreased with increasing age among people who inject drugs, while
      the opposite was true for chronic HBV. Persons with acute HBV were predominantly
      White (78%) while those with chronic HBV were mostly East Asian (60%). Relative
      to Whites, East Asians had 12 times greater odds of being diagnosed with chronic
      HBV infection. These odds increased with increasing socioeconomic deprivation.
      CONCLUSION: Differences in the profiles of people diagnosed with acute and
      chronic HBV infection necessitate differentiated screening, prevention, care and
      treatment programs.

PMID- 29568203
TI  - Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and
      premalignant hepatic lesions.
AB  - AIM: To assess the levels of different immune modulators in patients with
      hepatocellular carcinoma (HCC), in relation to other hepatic diseases. METHODS:
      Eighty-eight patients were included in the current study and represented patients
      with HCC (20), liver cirrhosis (28) and chronic hepatitis (CH; 25), and normal
      controls (NC; 15). Peripheral blood was isolated for immunophenotyping of active
      myeloid dendritic cells (mDCs; CD1c and CD40), mature inactive myeloid cells
      (CD1c and HLA), active plasmacytoid cells (pDCs; CD303 and CD40), mature inactive
      pDCs (CD30 and HLA), active natural killer (NK) cells (CD56 and CD161), active NK
      cells (CD56 and CD314) and inactive NK cells (CD56 and CD158) was done by flow
      cytometry. Serum levels of interleukin (IL)-2, IL-10, IL-12, IL-1beta, interferon
      (IFN)-alpha, IFN-gamma and tumor necrosis factor (TNF)-alphaR2 were assessed by
      ELISA. RESULTS: Active mDCs (CD1C+/CD40+) and inactive mDCs (CD1c+/HLA+) were
      significantly decreased in HCC patients in relation to NC (P < 0.001). CD40+
      expression on active pDCs was decreased in HCC patients (P < 0.001), and its
      level was not significantly changed among other groups. Inactive pDCs
      (CD303+/HLA+), inactive NKs (CD56+/CD158+) and active NKs (CD56+/CD161+) were not
      statistically changed among the four groups studied; however, the latter was
      increased in CH (P < 0.05). NKG2D was statistically decreased in HCC, CH and
      cirrhosis (P < 0.001), and it was not expressed in 63% (12/20) of HCC patients.
      There was significant decrease of IL-2, IFN-alpha and IFN-gamma (P < 0.001), and
      a significant increase in IL-10, IL-1beta, and TNF-alphaR2 (P <0.01, P < 0.001
      and P < 0.001; respectively) in HCC patients. There was inverted correlation
      between IL-12 and IL-1beta in HCC (r = -0.565, P < 0.01), with a strong
      correlation between pDCs (CD303+/CD40+) and NKs (CD56+/CD161+; r = 0.512, P <
      0.05) as well as inactive mDCs (CD1c+/HLA+) and inactive NK cells (CD56+/CD158+;
      r = 0.945, P < 0.001). CONCLUSION: NKG2D, CD40, IL-2 and IL-10 are important
      modulators in the development and progression of HCC.

PMID- 29568204
TI  - Serum autotaxin levels are correlated with hepatic fibrosis and ballooning in
      patients with non-alcoholic fatty liver disease.
AB  - AIM: To examine the relationship between serum autotaxin (ATX) concentrations and
      clinicopathological findings in non-alcoholic fatty liver disease (NAFLD)
      patients. METHODS: One hundred eighty-six NAFLD patients who had undergone liver
      biopsy between 2008 and 2017 were retrospectively enrolled. Serum samples were
      collected at the time of biopsy and ATX was measured by enzyme immunoassays. Sera
      obtained from 160 healthy, non-obese individuals were used as controls.
      Histological findings were graded according to an NAFLD scoring system and
      correlations with serum ATX were calculated by Spearman's test. Diagnostic
      accuracy was evaluated using the area under the receiver operating characteristic
      curve (AUC). Cut-off values were identified by the Youden index, and the nearest
      clinically applicable value to the cutoff was considered the optimal threshold
      for clinical convenience. RESULTS: Serum ATX levels were significantly higher in
      NAFLD patients than in controls (0.86 mg/L vs 0.76 mg/L, P < 0.001) and
      correlated significantly with ballooning score and fibrosis stage (r = 0.36, P <
      0.001 and r = 0.45, P < 0.001, respectively). Such tendencies were stronger in
      female patients. There were no remarkable relationships between ATX and serum
      alanine aminotransferase, lipid profiles, or steatosis scores. The AUC values of
      ATX for predicting the presence of fibrosis (>= F1), significant fibrosis (>=
      F2), severe fibrosis (>= F3), and cirrhosis (F4), were all more than 0.70 in
      respective analyses. CONCLUSION: Serum ATX levels may at least partially reflect
      histological severity in NAFLD.

PMID- 29568205
TI  - Epidemiological features of chronic hepatitis C infection caused by remunerated
      blood donors: A nearly 27-year period survey.
AB  - AIM: To understand the prevalence of hepatitis C virus (HCV) infection in blood
      donors over a nearly 27-year interval and to explore the factors that affect the
      outcome of HCV infection. METHODS: A retrospective and cross-sectional study was
      conducted. The participants, mostly plasma donors, were selected from three
      administrative villages in the Jiangsu province in Eastern China. A questionnaire
      was administered among the villagers who had a history of blood donation from the
      late 1980s to the early 1990s. All participants underwent physical examination,
      liver B-ultrasonography, and liver stiffness measurement. In addition, 10 mL of
      blood was collected from each participant to measure simple liver function
      parameters (albumin, alanine aminotransferase, aspirate aminotransferase), blood
      factors (platelet), and for hepatitis B surface antigen, antiHCV, and antihuman
      immunodeficiency virus detection. HCV RNA detection, HCV genotyping, and other
      tests were carried out in antiHCV-positive patients. RESULTS: After a median of
      27 years (25-31 years) from the last blood donation to the time of survey, a
      total of 1694 participants were investigated, and the antiHCV-positive
      individuals were categorized into three groups: blood donors (n = 12, 3.3%),
      plasma donors (n = 534, 68.5%), and mixed donors (n = 324, 58.8%). A total of 592
      (68.05%) patients had detectable HCV RNA, and 91.9% had genotype 1b. A total of
      161 (27.2%, 161/592) patients with chronic HCV were considered to have cirrhosis
      with a liver stiffness measurement level higher than 12 kPa. Multiple logistic
      (binary) regression analysis results showed that platelet and IgG levels were
      associated with cirrhosis. CONCLUSION: The nearly 27-year interval investigation
      revealed that chronic hepatitis C infection is a very serious public health
      problem in Eastern China. Plasma donation and subsequent return of blood cells to
      the donor are the main causes of hepatitis C infection. The main HCV genotype is
      1b. Nearly 28% of cases progressed to cirrhosis. Age, especially over 60 years,
      and regular drinking habits were risk factors associated with cirrhosis.

PMID- 29568206
TI  - Low-FODMAP vs regular rye bread in irritable bowel syndrome: Randomized
      SmartPill(r) study.
AB  - AIM: To compare the effects of regular vs low-FODMAP rye bread on irritable bowel
      syndrome (IBS) symptoms and to study gastrointestinal conditions with
      SmartPill(r). METHODS: Our aim was to evaluate if rye bread low in FODMAPs would
      cause reduced hydrogen excretion, lower intraluminal pressure, higher colonic pH,
      different transit times, and fewer IBS symptoms than regular rye bread. The study
      was a randomized, double-blind, controlled cross-over meal study. Female IBS
      patients (n = 7) ate study breads at three consecutive meals during one day. The
      diet was similar for both study periods except for the FODMAP content of the
      bread consumed during the study day. Intraluminal pH, transit time, and pressure
      were measured by SmartPill, an indigestible motility capsule. RESULTS: Hydrogen
      excretion (a marker of colonic fermentation) expressed as area under the curve
      (AUC)(0-630 min) was [median (range)] 6300 (1785-10800) ppm?min for low-FODMAP
      rye bread and 10 635 (4215-13080) ppm?min for regular bread (P = 0.028). Mean
      scores of gastrointestinal symptoms showed no statistically significant
      differences but suggested less flatulence after low-FODMAP bread consumption (P =
      0.063). Intraluminal pressure correlated significantly with total symptom score
      after regular rye bread (rho = 0.786, P = 0.036) and nearly significantly after
      low-FODMAP bread consumption (rho = 0.75, P = 0.052). We found no differences in
      pH, pressure, or transit times between the breads. Gastric residence of SmartPill
      was slower than expected. SmartPill left the stomach in less than 5 h only during
      one measurement (out of 14 measurements in total) and therefore did not follow on
      par with the rye bread bolus. CONCLUSION: Low-FODMAP rye bread reduced colonic
      fermentation vs regular rye bread. No difference was found in median values of
      intraluminal conditions of the gastrointestinal tract.

PMID- 29568209
TI  - Sharp Smith's bounds for the gamma function.
AB  - Among various approximation formulas for the gamma function, Smith showed that
      [Formula: see text] which is a little-known but accurate and simple one. In this
      note, we prove that the function [Formula: see text] is strictly increasing and
      concave on [Formula: see text], which shows that Smith's approximation is just an
      upper one.

PMID- 29568208
TI  - Low-pressure pneumoperitoneum with abdominal wall lift in laparoscopic total
      mesorectal excision for rectal cancer: Initial experience.
AB  - AIM: To evaluate the safety and feasibility of a new technology combining low
      pressure pneumoperitoneum (LPP) and abdominal wall lift (AWL) in laparoscopic
      total mesorectal excision (TME) for rectal cancer. METHODS: From November 2015 to
      July 2017, 26 patients underwent laparoscopic TME for rectal cancer using LPP (6
      8 mmHg) with subcutaneous AWL in Qilu Hospital of Shandong University, Jinan,
      China. Clinical data regarding patients' demographics, intraoperative monitoring
      indices, operation-related indices and pathological outcomes were prospectively
      collected. RESULTS: Laparoscopic TME was performed in 26 cases (14 anterior
      resection and 12 abdominoperineal resection) successfully, without conversion to
      open or laparoscopic surgery with standard-pressure pneumoperitoneum.
      Intraoperative monitoring showed stable heart rate, blood pressure and paw airway
      pressure. The mean operative time was 194.29 +/- 41.27 min (range: 125-270 min)
      and 200.41 +/- 20.56 min (range: 170-230 min) for anterior resection and
      abdominoperineal resection, respectively. The mean number of lymph nodes
      harvested was 16.71 +/- 5.06 (range: 7-27). There was no positive circumferential
      or distal resection margin. No local recurrence was observed during a median
      follow-up period of 11.96 +/- 5.55 mo (range: 5-23 mo). CONCLUSION: LPP combined
      with AWL is safe and feasible for laparoscopic TME. The technique can provide
      satisfactory exposure of the operative field and stable operative monitoring
      indices.

PMID- 29568207
TI  - Fatty liver in hepatitis C patients post-sustained virological response with
      direct-acting antivirals.
AB  - AIM: To determine steatosis and fibrosis prevalence in hepatitis C patients after
      a sustained virological response achieved with direct-acting antivirals. METHODS:
      Transient elastography with controlled attenuation parameter (CAP) was used to
      assess hepatic steatosis post-sustained virological response (SVR); the CAP
      technology was not available in the United States at study initiation. Liver
      stiffness/fibrosis was measured before and 47 wk after treatment completion.
      Patients with genotype 3 and patients with cirrhosis were excluded. RESULTS: One
      hundred and one patients were included in the study. Post-SVR there were
      decreases from baseline in alanine aminotransferase (ALT) (63.1 to 17.8 U/L),
      aspartate aminotransferase (51.8 to 21.5 U/L) and fibrosis score (7.4 to 6.1 kPa)
      (P < 0.05). Post-SVR, 48 patients (47.5%) had steatosis on CAP; of these, 6.25%
      had advanced fibrosis. Patients with steatosis had higher body mass index (29.0
      vs 26.1 kg/m2), glucose (107.8 vs 96.6 mg/dL), ALT (20.4 vs 15.3 mg/dL), CAP
      score (296.3 vs 212.4 dB/m) and fibrosis score (7.0 vs 5.3 kPa); P < 0.05.
      Interestingly, compared to baseline, both patients with and without steatosis had
      change in fibrosis score post-SVR (7.7 kPa vs 7.0 kPa and 7.0 kPa vs 5.3 kPa);
      alternatively, (P < 0.05) and therefore patients with steatosis continued to have
      clinically significant stiffness (>= 7 kPa). CONCLUSION: Fatty liver is very
      common in hepatitis C virus (HCV) patients post-SVR. These patients continue to
      have elevated mean fibrosis score (>= 7 kPa) compared to those without fatty
      liver; some have advanced fibrosis. Long term follow up is needed to assess
      steatosis and fibrosis in HCV patients post-SVR.

PMID- 29568210
TI  - Extensions of different type parameterized inequalities for generalized [Formula:
      see text]-preinvex mappings via k-fractional integrals.
AB  - The authors discover a general k-fractional integral identity with multi
      parameters for twice differentiable functions. By using this integral equation,
      the authors derive some new bounds on Hermite-Hadamard's and Simpson's
      inequalities for generalized [Formula: see text]-preinvex functions through k
      fractional integrals. By taking the special parameter values for various suitable
      choices of function h, some interesting results are also obtained.

PMID- 29568211
TI  - Monotonicity of the ratio of modified Bessel functions of the first kind with
      applications.
AB  - Let [Formula: see text] with [Formula: see text] be the modified Bessel functions
      of the first kind of order v. In this paper, we prove the monotonicity of the
      function [Formula: see text] on [Formula: see text] for different values of
      parameter p with [Formula: see text]. As applications, we deduce some new Simpson
      Spector-type inequalities for [Formula: see text] and derive a new type of bounds
      [Formula: see text] ([Formula: see text]) for [Formula: see text]. In particular,
      we show that the upper bound [Formula: see text] for [Formula: see text] is the
      minimum over all upper bounds [Formula: see text], where [Formula: see text] and
      is not comparable with other sharpest upper bounds. We also find such type of
      upper bounds for [Formula: see text] with [Formula: see text] and for [Formula:
      see text] with [Formula: see text].

PMID- 29568212
TI  - Effectiveness of Cognitive Behavioral Therapy for Individuals with Autism
      Spectrum Disorders and Comorbid Obsessive-Compulsive Disorder: A Review of the
      Research.
AB  - Autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD) are
      highly comorbid, precipitating an urgent need to identify evidence-based
      practices that might be used to address this comorbidity exclusively. The aim of
      this study was to conduct a review of intervention research and clinical reports
      to examine the use of cognitive behavioral therapy (CBT) with individuals who
      have comorbid ASD and OCD. Based on the pre-determined review inclusion criteria,
      11 studies were included in the review: three randomized control trials (RCT),
      one case controlled study, two single subject experimental designs, and five case
      studies. These studies offer promising data on the use of CBT interventions for
      individuals with ASD and comorbid OCD as well as for individuals with OCD and
      comorbid ASD when standard CBT protocol is enhanced with modifications such as
      parental involvement, increased use of visuals, personalized treatment metaphors,
      self-monitoring, positive reinforcement, and use of clear language and
      instructions. Limitations and implications for future research and practice are
      discussed.

PMID- 29568213
TI  - The Role of Organizational Control Systems in Employees' Organizational Trust and
      Performance Outcomes.
AB  - This study examined how organizational control is related to employees'
      organizational trust. We specifically focus on how different forms of control
      (process, outcome, and normative) relate to employees' trust in their employing
      organizations and examine whether such trust in turn relates positively to
      employee job performance (task performance and organizational citizenship
      behavior). In addition, and in response to the recommendations of past research,
      we examined these relationships in a high control and compliance-based cultural
      context. Using data from 105 employee-supervisor dyads from professional services
      firms in Singapore, we find support for our hypothesized model. The implications
      of the results for theory and practice, and directions for future research, are
      discussed.

PMID- 29568214
TI  - The Role of Occupational Identification During Post-Merger Integration.
AB  - Integration processes after mergers are fraught with difficulties, and constitute
      a main cause of merger failure. This study focuses on the human aspect of post
      merger integration, and in particular, on the role of occupational
      identification. We theorize and empirically demonstrate by means of a survey
      design that employees' identification with their occupation is positively related
      to their willingness to cooperate in the post-merger integration process, over
      and above the effect of organization members' organizational identification. This
      positive effect of occupational identification is stronger for uniformed
      personnel but attenuates in the course of the integration process. Qualitative
      interviews further explore and interpret the results from our statistical
      analysis. Together, these findings have important practical implications and
      suggest future research directions.

PMID- 29568215
TI  - Coworkers' Perspectives on Mentoring Relationships.
AB  - Research into workplace mentoring is primarily focused on the experiences and
      perceptions of individuals involved in the relationship, while there is scarcely
      any research focusing on the impact of mentoring relationships on their social
      environment. This exploratory research aims to give insight into how coworkers'
      perceptions and experiences of informal mentoring relationships in their
      workgroup are related to their perceptions of workgroup functioning. The results
      of 21 semistructured interviews show that coworkers believe that mentoring
      relationships affect their workgroup's functioning by influencing both their
      workgroup's performance and climate. Coworkers applied an instrumental
      perspective and described how they think that mentoring relationships both
      improve and hinder their workgroup's performance as they influence the individual
      functioning of mentor and protege, the workgroup's efficiency, and organizational
      outcomes. Furthermore, coworkers applied a relational perspective and described
      how mentoring relationships may influence their workgroup's climate in primarily
      negative ways as they may be perceived as a subgroup, cause feelings of distrust
      and envy, and are associated with power issues. The results of this study
      emphasize the importance of studying mentoring relationships in their broader
      organizational context and set the groundwork for future research on mentoring
      relationships in workgroups.

PMID- 29568216
TI  - Foster children's behavioral development and foster parent stress: testing a
      transactional model.
AB  - The goal of this three-wave longitudinal study was to analyze foster parent
      stress and foster children's internalizing and externalizing behaviors in a
      transactional framework. Participants in this study were 237 children in foster
      care in the Netherlands with, mostly, long placement durations (M = 56.86 months,
      SD = 49.10 months). We examined concurrent, prospective unidirectional and
      bidirectional relations between foster children's behavior and foster parent
      stress by using cross-lagged structural equation modeling and examined whether
      the results were stable across different subgroups of foster children. In
      contrast to our hypothesis, we found no bidirectional relations. There were
      unidirectional prospective pathways from foster children's internalizing and
      externalizing problems to foster parent stress, but no significant prospective
      pathways from foster parent stress to foster children's internalizing and
      externalizing problems. The results were fairly stable across different subgroups
      of foster children. The lack of bidirectional relations was unexpected given the
      presence of transactional relations in biological parent-child dyads. Foster
      parents seem not to influence their foster children when it comes to regulating
      problem behavior. Therefore, the question is whether foster parents can, in more
      general terms, help their foster children benefit from their improved home
      environment.

PMID- 29568218
TI  - Efficient Acceleration of the Pair-HMMs Forward Algorithm for GATK
      HaplotypeCaller on Graphics Processing Units.
AB  - GATK HaplotypeCaller (HC) is a popular variant caller, which is widely used to
      identify variants in complex genomes. However, due to its high variants detection
      accuracy, it suffers from long execution time. In GATK HC, the pair-HMMs forward
      algorithm accounts for a large percentage of the total execution time. This
      article proposes to accelerate the pair-HMMs forward algorithm on graphics
      processing units (GPUs) to improve the performance of GATK HC. This article
      presents several GPU-based implementations of the pair-HMMs forward algorithm. It
      also analyzes the performance bottlenecks of the implementations on an NVIDIA
      Tesla K40 card with various data sets. Based on these results and the
      characteristics of GATK HC, we are able to identify the GPU-based implementations
      with the highest performance for the various analyzed data sets. Experimental
      results show that the GPU-based implementations of the pair-HMMs forward
      algorithm achieve a speedup of up to 5.47* over existing GPU-based
      implementations.

PMID- 29568217
TI  - Mutational screening of germline RB1 gene in Vietnamese patients with
      retinoblastoma reveals three novel mutations.
AB  - Purpose: Retinoblastoma (Rb) is a rare and unique eye cancer that usually
      develops in the retinas of children less than 5 years old due to mutations in the
      RB1 gene. About 40% of affected individuals have the heritable form making
      genetics testing of the RB1 gene important for disease management. This study
      aims to identify germline mutations in RB1 in a cohort of patients with Rb from
      northern Vietnam. Methods: Genomic DNA was extracted from peripheral blood of 34
      patients with Rb (nine unilateral and 25 bilateral cases) and their available
      parents. Twenty-seven exons, flanking sequences, and the promoter region of RB1
      gene were screened for mutations with direct PCR sequencing. Multiplex ligation
      dependent probe amplification (MLPA) was applied for patients with negative
      sequencing results. In the mutation-positive patients, their available parental
      DNA was analyzed to determine the parental origin of the mutation. Results:
      Germline mutations in RB1 were identified in 25 (73.53%) of 34 patients (four
      unilateral and 21 bilateral cases). Of these mutations, 19 were detected,
      including seven nonsense, six frameshift, four splice-site (one was identified in
      two siblings), and one missense, with Sanger sequencing. Three novel frameshift
      mutations were discovered in one unilateral and two bilateral patients. MLPA
      detected mutations in the RB1 gene in six bilateral cases, of whom five had a
      whole gene deletion (three familial cases) and one had a partial gene deletion
      (from exon 4 to exon 27) in one allele of the RB1 gene. Parental testing showed
      five mutations originated from the fathers and one was inherited from a mother
      who was mosaic for the mutation. Conclusions: This study provides a data set of
      germline mutations in the RB1 gene in Vietnamese patients with retinoblastoma.
      Screening of mutations in the RB1 gene can help to identify heritable Rb and
      contribute to clinical management and genetic counseling for affected families.

PMID- 29568219
TI  - Technical Validation of a Reverse-Transcription Quantitative Polymerase Chain
      Reaction In Vitro Diagnostic Test for the Determination of MiR-31-3p Expression
      Levels in Formalin-Fixed Paraffin-Embedded Metastatic Colorectal Cancer Tumor
      Specimens.
AB  - MiR-31-3p expression has been shown to be a predictive biomarker for response to
      anti-epithelial growth factor receptor therapy in patients with RAS wild-type
      metastatic colorectal cancer (mCRC). To aid in the quantification of miR-31-3p
      expression in formalin-fixed paraffin-embedded (FFPE) primary tumor samples from
      patients with mCRC, a reverse-transcription quantitative polymerase chain
      reaction (RT-qPCR) assay was developed and validated. Assay development included
      the identification of a microRNA reference standard and the determination of an
      appropriate relative quantification cutoff for differentiating low versus high
      miR-31-3p expression. Sample specimens for the validation studies included both
      FFPE slides and shavings. Polymerase chain reaction (PCR) efficiency and
      linearity, analytical sensitivity and specificity, assay robustness,
      reproducibility, and accuracy were demonstrated across a number of test
      conditions and differing quantitative PCR platforms. The data from this study
      provide evidence as to the feasibility of quantifying the expression of miR-31-3p
      from FFPE tumor tissue using a standardized RT-qPCR assay.

PMID- 29568220
TI  - Lipophosphoglycan 3 From Leishmania infantum chagasi Binds Heparin With
      Micromolar Affinity.
AB  - Leishmania infantum chagasi is an intracellular protozoan parasite responsible
      for visceral leishmaniasis, a fatal disease in humans. Heparin-binding proteins
      (HBPs) are proteins that bind to carbohydrates present in glycoproteins or
      glycolipids. Evidence suggests that HBPs present on Leishmania surface
      participate in the adhesion and invasion of parasites to tissues of both
      invertebrate and vertebrate hosts. In this study, we identified the product with
      an HSP90 (heat shock protein 90) domain encoded by lipophosphoglycan (LPG3) gene
      as a L infantum chagasi HBP (HBPLc). Structural analysis using the LPG3
      recombinant protein suggests that it is organized as a tetramer. Binding analysis
      confirms that it is capable of binding heparin with micromolar affinity.
      Inhibition of adenosine triphosphatase activity in the presence of heparin,
      molecular modeling, and in silico docking analysis suggests that heparin-binding
      site superimposes with the adenosine triphosphate-binding site. Together, these
      results show new properties of LPG3 and suggest an important role in
      leishmaniasis.

PMID- 29568221
TI  - Can We Predict Which Adolescents Will Engage in Outpatient Substance Abuse
      Treatment?
AB  - Understanding which adolescents remain in substance abuse treatment may
      facilitate the development of effective strategies for enhancing engagement and
      retention. Using clinical service data from a large naturalistic sample of
      adolescents, we examined whether client characteristics predict retention in
      outpatient alcohol and other drug (AOD) treatment. chi2 tests and multinomial
      logistic regressions were conducted to examine relationships between
      sociodemographic and substance use variables and clinic attendance. Client
      characteristics of ethnicity, sex, age, living situation (whether living with or
      away from family), and substance use severity were associated with retention in
      community AOD treatment. Pacific Island youth, females, 13- to 15-year olds,
      clients living with family, and clients with more severe substance use were
      generally more likely to be "engaged" with the service (ie, attended 4+ sessions)
      than their European and Maori, male, 16- to 19-year-old, and living away from
      home counterparts. These findings may inform more targeted engagement strategies
      in the future.

PMID- 29568222
TI  - Severe Myopericarditis in Diabetic Ketoacidosis-All Troponin are Not Myocardial
      Infarction.
AB  - Uncontrolled diabetes and acute coronary syndrome share a complex dynamic that
      results in significant ambiguity when interpreting biomarker elevations in this
      setting. This is concerning because myocardial infarction has been shown to be
      the most common cause of death in the first 24 hours of admission for
      uncontrolled diabetes. Literature shows that elevation in cardiac biomarkers in
      patients with uncontrolled diabetes could be from viral myopericarditis, although
      a clear clinical significance is still lacking.1 It is, however, clear that
      elevation in cardiac biomarkers portends a poor long-term prognosis in patients
      with uncontrolled diabetes mellitus. We present a rare case of myopericarditis in
      a middle-aged patient with uncontrolled diabetes. The patient had elevated
      troponin I level reaching a peak of 7.3 ng/mL with associated ST elevations on
      electrocardiography. Coronary angiogram was subsequently done revealing clean
      coronaries. To our knowledge, this is the first description of myopericarditis in
      uncontrolled diabetes without a known cause.

PMID- 29568223
TI  - Acquired von Willebrand Syndrome Complicating Nephrotic Syndrome: A Case of a
      Patient With Membranous Nephropathy.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare clinical entity presenting with
      heterogeneous hemorrhagic manifestations, although some subsets of patients with
      AVWS may be asymptomatic until they are exposed to major trauma, an invasive
      procedure, or surgery. We herein report one such case in a 73-year-old male
      patient with nephrotic syndrome with a prolonged active partial thromboplastin
      time. We initially did not deal with this distinct abnormal clotting profile
      seriously, but persistent bleeding after a retroperitoneoscopic-assisted renal
      biopsy that allowed us to ascribe his nephrotic syndrome to membranous
      nephropathy fortuitously led to the discovery of concurrent AVWS. We feel that an
      accurate and prompt diagnosis as well as awareness of the disease remain a
      challenge for physicians and therefore strongly recommend the further
      accumulation of experiences similar to our own in a prospective manner. This
      report underscores the pitfalls associated with determining the bleeding risk,
      including an insufficient assessment and improper weighting of an abnormal
      clotting profile prior to the invasive procedure. Several management concerns
      that emerged in the current case are also discussed.

PMID- 29568224
TI  - Visualization of JOV abstracts.
AB  - Abstract: Since the abstract can be found at the beginning of most scientific
      articles and is an essential part of the article, several attempts have been made
      to explore the rhetorical moves of abstracts in various research fields. These
      studies dealt only with accepted articles since they can be easily accessed.
      Although the findings of such works have some pedagogical implications for
      academic writing courses for young researchers who are relatively new to their
      fields, they do not contribute enough to the transparency of the peer review
      processes conducted in research fields. Increasing transparency requires
      considering rejected articles since they help to clarify the decision criteria in
      the peer review. Based on 591 abstracts of accepted or rejected articles
      submitted to Journal of Visualization (JOV), the present study aimed at exploring
      the differences between the accepted and rejected abstracts. The results show
      that there are significant differences in the structures of the abstracts. Since
      we also successfully develop a classification model for the decision using a
      machine-learning technique, the findings of this study have some implications for
      developing a semi-automatic reviewing system that can reduce the reviewer's
      burden and increase the review quality. Graphical abstract: 

PMID- 29568225
TI  - Politics of policy learning: Evaluating an experiment on free pricing
      arrangements in Dutch dental care.
AB  - In Dutch healthcare, new market mechanisms have been introduced on an
      experimental basis in an attempt to contain costs and improve quality. Informed
      by a constructivist approach, we demonstrate that such experiments are not
      neutral testing grounds. Drawing from semi-structured interviews and policy
      texts, we reconstruct an experiment on free pricing in dental care that turned
      into a critical example of market failure, influencing developments in other
      sectors. Our analysis, however, shows that (1) different market logics and (2)
      different experimental logics were reproduced simultaneously during the course of
      the experiment. We furthermore reveal how (3) evaluation and political life
      influenced which logics were reproduced and became taken as the lessons learned.
      We use these insights to discuss the role of evaluation in learning from policy
      experimentation and close with four questions that evaluators could ask to better
      understand what is learned from policy experiments, how, and why.

PMID- 29568226
TI  - Diagnosing sex: Intersex surgery and 'sex change' in Britain 1930-1955.
AB  - The medical 'management' of individuals with atypical sex characteristics, or
      intersex variations, has been under scrutiny since the beginnings of intersex
      activism in the 1990s. This article explores a history of intersex surgeries in
      Britain and the interaction with medical and popular discourses around 'sex
      change' between 1930 and 1955. A focus on this period in Britain helps to
      critically elaborate on debates in intersex scholarship; provides historical
      context for the introduction of approaches and protocols based on John Money and
      colleagues' work in the USA in the mid-century; and analyses a long history of
      tension and intersection between trans and intersex experiences, treatments,
      politics and popular representations that continue into the present.

PMID- 29568227
TI  - Is there a parliamentary peace? Parliamentary veto power and military
      interventions from Kosovo to Daesh.
AB  - This article studies the effect of parliamentary involvement on security policy.
      Building on Democratic Peace Theory, it examines whether democracies with a
      parliamentary veto power are indeed less likely to participate in military
      interventions, than democracies without such a veto power, ceteris paribus. By
      studying patterns of participation across 25 to 35 countries in five military
      missions, this paper finds modest evidence for such a parliamentary peace and
      suggests that it depends on the character of the military mission in question. If
      a mission is framed as a test case of alliance solidarity, as was the case with
      OEF and the Iraq War, domestic institutional constraints can be trumped by
      alliance politics. If, however, countries enjoy more discretion in deciding on
      the use of force, domestic constraints such as parliamentary war powers have a
      tangible impact on government policy.

PMID- 29568228
TI  - Dissecting the complex regulation of lodging resistance in Brassica napus.
AB  - Lodging continues to be a major cause of yield loss in important crop species
      such as Brassica napus. Understanding the genetic regulation of lodging
      resistance is therefore of key interest to breeders worldwide. Current strategies
      aimed at minimising lodging risk involve the incorporation of dwarfing genes or
      the application of plant growth regulators. However, despite these efforts,
      lodging continues to be a persistent problem and it is therefore of high interest
      that novel, complimentary strategies for lodging control are implemented. One
      approach would be to focus on understanding the genetic properties underlying
      stem mechanical strength. With this in mind, we screened a training genetic
      diversity panel of B. napus accession for variation in stem mechanical strength
      and related traits. Using Associative Transcriptomics, we identified molecular
      markers for a suite of valuable traits. Using an independent test genetic
      diversity panel, we show that the methods employed are robust for identification
      of predictive markers. Furthermore, based on conserved synteny with Arabidopsis
      thaliana, we are able to provide a biological context to the marker associations
      detected and provide evidence for a role in pectin methylesterification in
      contributing to stem mechanical strength in Brassicaceae.

PMID- 29568229
TI  - Genetic analysis and QTL mapping of the seed hardness trait in a black common
      bean (Phaseolus vulgaris) recombinant inbred line (RIL) population.
AB  - Seed hardness trait has a profound impact on cooking time and canning quality in
      dry beans. This study aims to identify the unknown genetic factors and associated
      molecular markers to better understand and tag this trait. An F2:7 recombinant
      inbred line (RIL) population was derived from a cross between the hard and soft
      seeded black bean parents (H68-4 and BK04-001). Eighty-five RILs and the parental
      lines were grown at two locations in southern Manitoba during years 2014-2016.
      Seed samples were harvested manually at maturity to test for seed hardness
      traits. The hydration capacity and stone seed count were estimated by soaking the
      seeds overnight at room temperature following AACC method 56-35.01. Seed samples
      from 2016 tests were also cooked to determine effect of seed hardness on cooking
      quality. For mapping of genomic regions contributing to the traits, the RIL
      population was genotyped using the genotype by sequencing (GBS) approach. The QTL
      mapping revealed that in addition to the major QTL on chromosome 7 at a genomic
      location previously reported to affect seed-hydration, two novel QTL with
      significant effects were also detected on chromosomes 1 and 2. In addition, a
      major QTL affecting the visual appeal of cooked bean was mapped on chromosome 4.
      This multi-year-site study shows that despite large environmental effects, seed
      hardness is an oligo-genic and highly heritable trait, which is inherited
      independently of the cooking quality scored as visual appeal of cooked beans. The
      identification of the QTLs and development of SNP markers associated with seed
      hardness can be applied for common bean variety improvement and genetic
      exploitation of these traits.

PMID- 29568231
TI  - Birth preparedness and complication readiness among pregnant women in Tehulederie
      district, Northeast Ethiopia: a community-based cross-sectional study.
AB  - Background: Motherhood is a time of anticipation of joy for a woman, her family,
      and her community. In spite of this fact, it is not as enjoyable as it should be
      because of numerous reasons. Insufficiency or lack of birth preparedness and
      complication readiness is the most common reason. The aim of this study was to
      assess the practice of birth preparedness and complication readiness and
      associated factors among pregnant women in Tehuledere district, northeast
      Ethiopia. Methods: A community-based cross-sectional study was conducted in
      Tehuledere district, northeast Ethiopia. Participants were selected using the
      multistage sampling technique, and data were analyzed both descriptively and
      analytically using the binary logistic regression. Result: Out of the total 507
      samples, 500 (response rate 98.6%) pregnant women participated in the study. Less
      than half (44.6%) and (43.4%) of the respondents had knowledge and practice on
      birth preparedness and complication readiness, respectively. In the multivariate
      analysis, knowledge of birth preparedness and complication readiness (AOR =
      1.648, 95%CI: 1.073, 2.531), knowledge of danger signs during pregnancy (AOR =
      2.802, 95% CI: 1.637, 4.793), gestational age (AOR = 3.379, 95% CI: 2.114,
      5.401), and antenatal care follow up starting time (AOR = 2.841, 95% CI: 1.330,
      6.068) were significantly associated with the practice of birth preparedness and
      complication readiness, but pregnant women in rural areas (AOR = 0.442, 95%
      CI:0.244, 0.803) were less associated with birth preparedness and complication
      readiness compared to women in urban settlements. Conclusion: This study
      identified that poor knowledge, inadequate birth preparedness, and complication
      readiness were prevalent among mothers in the study area. Government officials,
      partners, and health care providers working in the areas of maternal and child
      health should operate together to maximize birth preparedness and complication
      readiness practices.

PMID- 29568230
TI  - Azo group(s) in selected macrocyclic compounds.
AB  - Azobenzene derivatives due to their photo- and electroactive properties are an
      important group of compounds finding applications in diverse fields. Due to the
      possibility of controlling the trans-cis isomerization, azo-bearing structures
      are ideal building blocks for development of e.g. nanomaterials, smart polymers,
      molecular containers, photoswitches, and sensors. Important role play also
      macrocyclic compounds well known for their interesting binding properties. In
      this article selected macrocyclic compounds bearing azo group(s) are
      comprehensively described. Here, the relationship between compounds' structure
      and their properties (as e.g. ability to guest complexation, supramolecular
      structure formation, switching and motion) is reviewed.

PMID- 29568232
TI  - Challenges faced by nurses in using pain assessment scale in patients unable to
      communicate: a qualitative study.
AB  - Background: One helpful strategy adopted for pain management in non-verbal,
      intubated patients is the use of a proper pain assessment scale. The purpose of
      the present study is to achieve a better and deeper understanding of the existing
      nurses' challenges in using pain assessment scales among patients unable to
      communicate. Methods: This qualitative study was conducted using content
      analysis. Purposive sampling was used to select the participants and continued
      until data saturation. The participants included 20 nurses working in intensive
      care units. Data was collected using semi-structured interviews and analysis was
      done using an inductive approach. Results: Four categories and ten sub-categories
      were extracted from the experiences of the nurses working in the intensive care
      units in terms of nursing challenges in using non-verbal pain assessment scales.
      The four categories included "forgotten priority", "organizational barriers",
      "attitudinal barriers", and "barriers to knowledge". Conclusions: The findings of
      the present study have shown that various factors might influence on the use of
      non-verbal pain assessment scales in patients unable to communicate. Identifying
      these challenges for nurses can help take effective steps such as empowering
      nurses in the use of non-verbal pain assessment scales, relieving pain, and
      improving the quality of care services.

PMID- 29568233
TI  - The long non-coding RNA AK001796 contributes to tumor growth via regulating
      expression of p53 in esophageal squamous cell carcinoma.
AB  - Background: Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and
      deadly cancers worldwide, especially in China. Considering the poor prognosis of
      ESCC, the aim of this study is to dissect the effects of long non-coding RNA
      (lncRNA) AK001796 on cell proliferation and cell cycle in vitro and
      tumorigenicity in vivo, providing therapeutic targets for ESCC. Methods: We
      conducted quantitative real time PCR to detect the expression level of lncRNA
      AK001796 in human ESCC tumor and adjacent non-tumor tissues, and analyzed the
      correlation between lncRNA AK001796 expression and clinicopathologic feature of
      ESCC patients. Then we knocked down the expression of lncRNA AK001796 in human
      ESCC cell lines Eca-109 and TE-1, and next inspected cell cycle and apoptosis
      condition in these cells using flow cytometry. Subsequently, we used CCK-8 assay
      to test proliferation ability of the lncRNA AK001796-silenced ESCC cells, and the
      MDM2/p53 signaling pathway in these cells was analyzed by western blot analysis.
      At last, the ESCC xenograft models were established to verify the role of lncRNA
      AK001796 on the occurrence and development of ESCC. Results: In this study, we
      demonstrated that lncRNA AK001796 was significantly upregulated in ESCC tumor
      tissues compared to adjacent non-tumor tissues. Knockdown of lncRNA AK001796
      inhibited ESCC cell growth, cell cycle, and tumor growth in a xenograft mouse
      model via regulating MDM2/p53 signal pathway. The expression of lncRNA AK001796
      was positively correlated with MDM2 levels in human ESCC samples. Conclusions:
      Overall, lncRNA AK001796 regulates cell proliferation and cell cycle via
      modulating MDM2/p53 signaling in ESCC, which provides a new insight into the
      treatment targets for ESCC.Trial registration This study was registrated in the
      Ethics Committee of the First Affiliated Hospital of Nanjing Medical University
      (Trial registration: 2012-SR-127, Registered 20 January 2012).

PMID- 29568234
TI  - Downregulation of microRNA-21 inhibited radiation-resistance of esophageal
      squamous cell carcinoma.
AB  - Background: MicroRNA-21 (miR-21) was previously reported being dysregulated in
      many kinds of cancer including esophageal squamous cell carcinoma (ESCC). In the
      present study, we aimed to investigate the role of miR-21 in ESCC, especially in
      its effects on radiation-sensitivity of ESCC. Methods: Expression of miR-21 was
      detected in 63 pairs ESCC tumor and adjacent non-tumoral tissues using qRT-PCR,
      correlation between miR-21 and clinicopathological feature of ESCC was analyzed.
      The role of miR-21 in the proliferation, cell cycle and apoptosis of ESCC cells
      during irradiation were studied. Results: MicroRNA-21 expression was
      significantly increased in ESCC tumor tissues. Expression of miR-21 was
      positively associated with advanced clinical stage. Under irradiation,
      overexpression of miR-21 increased cell proliferation and cells in S phase, and
      inhibited cell apoptosis of ESCC cells. In contrast, knockdown of miR-21 had an
      opposite effect. Conclusions: Downregulation of miR-21 inhibited the radiation
      resistance of ESCC, whereas overexpression of miR-21 increased the radiation
      resistance. MiR-21 is a potential novel target for developing specific treatment
      interventions in ESCC in future.

PMID- 29568235
TI  - Transcription factor E2F3a regulates CASP8AP2 transcription and enhances
      sensitivity to chemotherapeutic drugs in acute lymphoblastic leukemia.
AB  - Background: Low expression of E2F3a and caspase 8 associated protein 2 (CASP8AP2)
      are associated with poor prognosis of childhood acute lymphoblastic leukemia
      (ALL). Methods: Dual-luciferase reporter assay and wild type as well as four
      mutated types of reporter plasmids were used to demonstrate the activation of
      E2F3a on CASP8AP2 transcription. The direct binding of E2F3a with the promoter of
      CASP8AP2 was shown by Chromatin Immunoprecipitation (ChIP). Cell proliferation
      activity and cell cycle were determined by MTS and flow cytometry in leukemic
      cells after treating with common chemotherapeutic drugs vincristine and
      daunorubicin. Results: In this study, we found that up-regulation of E2F3a in
      leukemic cells led to increased fraction of cells in S and G2/M phase,
      accelerated proliferation, and enhanced sensitivity to vincristine and
      daunorubicin. ChIP and luciferase assay indicated that E2F3a could directly bind
      to two fragments in the wild type of CASP8AP2 promotor (- 206 to - 69 and - 677
      to - 507), and activate its transcription activity which was reduced in mutated
      promotors. The effect of E2F3a on chemotherapeutic sensitivity of leukemic cells
      could be reversed by down-regulating CASP8AP2. Conclusions: E2F3a could promote
      transcription and expression of CASP8AP2. The effect of E2F3a on chemotherapeutic
      sensitivity of ALL cells was implemented by regulating CASP8AP2 expression to a
      great extent.

PMID- 29568236
TI  - Alteration of metabolite profiling by cold atmospheric plasma treatment in human
      myeloma cells.
AB  - Background: Despite new progress of chemotherapy in multiple myeloma (MM)
      clinical treatment, MM is still a refractory disease and new technology is needed
      to improve the outcomes and prolong the survival. Cold atmospheric plasma is a
      rapidly developed technology in recent years, which has been widely applied in
      biomedicine. Although plasma could efficiently inactivate various tumor cells,
      the effects of plasma on tumor cell metabolism have not been studied yet.
      Methods: In this study, we investigated the metabolite profiling of He plasma
      treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF)
      mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG
      analysis we try to figure out the metabolism pathway that was significantly
      affected by gas plasma treatment. Results: By GC-TOF mass-spectrometry, 573
      signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we
      listed all the differential metabolites and further classified into different
      metabolic pathways. The results showed that beta-alanine metabolism pathway was
      the most significant change after He gas plasma treatment in myeloma cells.
      Besides, propanoate metabolism and linoleic acid metabolism should also be
      concerned during gas plasma treatment of cancer cells. Conclusions: Cold
      atmospheric plasma treatment could significantly alter the metabolite profiling
      of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the
      most susceptible to He gas plasma treatment.

PMID- 29568238
TI  - In comparative perspective: The effects of incarceration abroad on penal
      subjectivity among prisoners in Lithuania.
AB  - This article looks at how global flows of people and policies affect penal
      subjectivity among prisoners in Lithuania. Those who had previously been
      incarcerated abroad perceive their punishment in Lithuania's reforming penal
      system in comparative terms. We find that international prison experience may
      either diminish or increase the sense of the severity of the current punishment.
      Respondents often felt more comfortable in a familiar culture of punishment in
      Lithuania that emphasizes autonomy and communality. Moreover, internationalized
      prisoners perceive prison reform emulating West European models as a threat to
      this culture and are able to articulate comparative critiques of this reform and
      contest its effects.

PMID- 29568237
TI  - Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: an
      insight.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality,
      accounting for almost 90% of total liver cancer burden. Surgical resection
      followed by adjuvant and systemic chemotherapy are the most meticulously followed
      treatment procedures but the complex etiology and high metastatic potential of
      the disease renders surgical treatment futile in majority of the cases. Another
      hindrance to the scenario is the acquired resistance to drugs resulting in
      relapse of the disease. Hence, to provide insights into development of novel
      therapeutic targets and diagnostic biomarkers, this review focuses on the various
      molecular mechanisms underlying chemoresistance in HCC. We have provided a
      comprehensive summary of the various strategies adopted by HCC cells, extending
      from apoptosis evasion, autophagy activation, drug expulsion to epigenetic
      transformation as modes of therapy resistance. The role of stem cells in
      imparting chemoresistance is also discussed. Furthermore, the review also focuses
      on how this knowledge might be exploited for the development of an effective,
      prospective therapy against HCC.

PMID- 29568239
TI  - Effects of the complete replacement of fish oil with linseed oil on growth, fatty
      acid composition, and protein expression in the Chinese mitten crab (Eriocheir
      sinensis).
AB  - Background: The finite marine resources make it difficult for us to obtain enough
      fish oil (FO) used in aquatic feeds. Another sustainable ingredients should be
      found to substitute FO. The effects of replacing FO with vegetable oil have been
      studied in a variety of crustaceans, but most studies have focused on the
      phenotypic effects. Little is known about the mechanisms of the effects. Methods:
      To understand the molecular responses during the replacement of FO in Eriocheir
      sinensis, we investigated the effects of feeding FO or linseed oil (LO) on growth
      performance, digestive enzyme activity, fatty acid composition and protein
      expression in E. sinensis. Twenty-four juvenile crabs were fed diets containing
      FO or LO for 112 days. Weight, carapace length and width were recorded. Fatty
      acid composition of the diets and the hepatopancreas and protein expression in
      the hepatopancreas were analyzed. Results: Growth performance and molting
      interval were unchanged by diet. Crabs fed FO and LO had same activity of lipase
      and amylase, but comparing with crabs fed LO, crabs fed FO had higher trypsin
      activity and lower pepsin activity. Hepatopancreas fatty acid composition changed
      to reflect the fatty acid composition of the diets. In total, 194 proteins were
      differentially expressed in the hepatopancreas between the diets. Expression of
      heat shock proteins was higher in crabs fed LO. Expression of fatty acid
      synthase, long-chain fatty acid transport protein 4, acyl-CoA delta-9 desaturase,
      and fatty acid-binding protein 1, was higher in crabs fed FO. Conclusions: The
      substitution of FO with LO didn't have any effects on the growth and molting of
      mitten crab, but could significantly decrease the ability of mitten crab to cope
      with stress. The high content of HUFAs in the hepatopancreas of mitten crab fed
      FO is due to the high abundance of the proteins relative to the transport of the
      HUFAs. These findings provide a reason of the high content of EPA and DHA in
      crabs fed with FO, and provide new information for the replacement of FO in diets
      of mitten crab.

PMID- 29568240
TI  - Differential impact of diabetes mellitus on antiplatelet effects of prasugrel and
      clopidogrel.
AB  - Background: Although prasugrel exerts stronger antiplatelet effects compared with
      clopidogrel, the factors affecting platelet reactivity under prasugrel have not
      been fully determined. This study aimed to find the novel mechanistic differences
      between two thienopyridines and identify the factor that influence platelet
      reactivity to each drug. Methods: Forty patients with stable angina who underwent
      elective percutaneous coronary intervention were randomly assigned to receive
      either prasugrel (20 mg) or clopidogrel (300 mg) as a loading dose. Platelet
      function (light transmission, laser light scattering, and vasodilator-stimulated
      phosphoprotein phosphorylation) and plasma active metabolite levels were measured
      after the loading dose. Results: Prasugrel consistently inhibited adenosine
      diphosphate receptor P2Y12 signalling to abolish amplification of platelet
      aggregation. Prasugrel abolished even small platelet aggregates composed of less
      than 100 platelets. On the other hand, clopidogrel inhibited large aggregates but
      increased small and medium platelet aggregates. Diabetes was the only independent
      variable for determining antiplatelet effects and active metabolite concentration
      of prasugrel, but not clopidogrel. Sleep-disordered breathing was significantly
      correlated with platelet reactivity in patients who had clopidogrel. Conclusions:
      Prasugrel efficiently abolishes residual P2Y12 signalling that causes small
      platelet aggregates, but these small aggregates are not inhibited by clopidogrel.
      Considering the differential effect of diabetes on antiplatelet effects between
      these two drugs, the pharmacokinetics of prasugrel, other than cytochrome P450
      metabolism, might be affected by diabetes. Trial registration: UMIN-CTR
      UMIN000017624, retrospectively registered 21 May 2015.

PMID- 29568241
TI  - Cognitive-Behavioral Group Therapy for Latino youth with Type 1 Diabetes and
      depression: A case study.
AB  - This group case study describes the course of a 14-session Cognitive Behavioral
      Therapy (CBT) for Latino adolescents with Type 1 Diabetes Mellitus (T1DM) and
      depressive symptoms. The intervention, known as CBT-DM, is an adaptation of an
      efficacious group intervention for adolescent depression. The treatment rationale
      and cultural adaption model are described as well as procedures used to achieve
      sensitivity to the characteristics of the T1DM culture as experienced by Latino
      youth from Puerto Rico. Session-by-session protocol is reviewed and treatment
      gains on the group as a whole and on its individual members are presented,
      providing quantitative and qualitative data. Treatment feasibility, clients'
      acceptance and satisfaction with treatment, and follow-up data up to 6 months
      post-treatment are also examined, considering cognitive, behavioral, emotional,
      relational, medical, and functional outcomes. Complicating factors, barriers to
      care, and treatment implications are discussed in the context of treating clients
      with comorbid chronic physical illness and emotional problems also embedded in a
      Latino culture. Translation of evidence-based treatments for depression into
      primary care settings and adapting protocols to youth populations with other
      medical illnesses is proposed. Recommendations for clinicians are provided,
      emphasizing the establishment of collaborative relationships with clients,
      assessing their stage in the process of accepting their chronic illness, as well
      as understanding their overall context to avoid unnecessary attributions of
      pathology to their thoughts, behaviors, and feelings.

PMID- 29568242
TI  - R2GUESS: A Graphics Processing Unit-Based R Package for Bayesian Variable
      Selection Regression of Multivariate Responses.
AB  - Technological advances in molecular biology over the past decade have given rise
      to high dimensional and complex datasets offering the possibility to investigate
      biological associations between a range of genomic features and complex
      phenotypes. The analysis of this novel type of data generated unprecedented
      computational challenges which ultimately led to the definition and
      implementation of computationally efficient statistical models that were able to
      scale to genome-wide data, including Bayesian variable selection approaches.
      While extensive methodological work has been carried out in this area, only few
      methods capable of handling hundreds of thousands of predictors were implemented
      and distributed. Among these we recently proposed GUESS, a computationally
      optimised algorithm making use of graphics processing unit capabilities, which
      can accommodate multiple outcomes. In this paper we propose R2GUESS, an R package
      wrapping the original C++ source code. In addition to providing a user-friendly
      interface of the original code automating its parametrisation, and data handling,
      R2GUESS also incorporates many features to explore the data, to extend
      statistical inferences from the native algorithm (e.g., effect size estimation,
      significance assessment), and to visualize outputs from the algorithm. We first
      detail the model and its parametrisation, and describe in details its optimised
      implementation. Based on two examples we finally illustrate its statistical
      performances and flexibility.

PMID- 29568243
TI  - Effects of a high-fat diet on superoxide anion generation and membrane fluidity
      in liver mitochondria in rats.
AB  - Background: Obesity is a primary factor of lifestyle-related diseases, and the
      age of its onset has decreased. The reactive oxygen species (ROS), the superoxide
      anion, is generated in the mitochondrial electron transport chain and the damage
      it induces in cells may be a contributing factor to obesity-related lifestyle
      diseases. In the present study, the influence of the ingestion of a high-fat diet
      (HFD) on superoxide anion generation in rat liver mitochondria (Mt) and membrane
      fluidity was investigated. Methods: Male Wistar rats were fed a normal diet (ND,
      n = 6) or HFD (n = 6). Liver Mt were isolated and oxygen consumption, superoxide
      anion production (the adrenaline method), and membrane fluidity (the spin label
      method) were measured. Results: After 11 weeks, body weights and abdominal
      circumferences were higher in the HFD group than in the ND group. Mt oxygen
      consumption was higher in the HFD group than in the ND group. Superoxide anion
      production was significantly lower in the HFD group than in the ND group, while
      no significant changes were observed in membrane fluidity. Conclusion: Although
      rats developed diet-induced obesity, it did not reach the level of disease
      development. The promotion of lipid metabolism appeared to reduce superoxide
      anion production, but did not influence membrane fluidity. While superoxide anion
      damages cells as an oxidative stress, ROS and superoxide dismutase are essential
      signaling molecules in the body. The present results suggest that the continuous
      ingestion of a HFD impairs Mt and induces disease development.

PMID- 29568245
TI  - Carboxyl of Poly(D,L-lactide-co-glycolide) Nanoparticles of Perfluorooctyl
      Bromide for Ultrasonic Imaging of Tumor.
AB  - Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic
      contrasts have shown promising results in the recent years. However, NPs display
      poor contrast enhancement in vivo. In this work, we used the copolymers
      poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co-
      glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to
      encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small
      and uniform (210.6 +/- 2.9 nm with a polydispersity index of 0.129 +/- 0.016)
      with a complete shell nuclear structure under the transmission electron
      microscopy (TEM). In vitro, when concentration of NPs was >=10 mg/ml and clinical
      diagnostic frequency was >=9 MHz, NPs produced intensive enhancement of
      ultrasonic gray-scale signals. NPs could produce stable and obvious gray
      enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered
      good ultrasound enhancement in tumor after more than 24 h and optical imaging
      also indicated that NPs were mainly located at tumor site. Subsequent analysis
      confirmed that large accumulation of fluorescence was observed in the frozen
      section of the tumor tissue. All these results caused the conclusion that NPs
      encapsulated PFOB has achieved tumor-selective imaging in vivo.

PMID- 29568246
TI  - Binary similarity measures for fingerprint analysis of qualitative metabolomic
      profiles.
AB  - Introduction: Contemporary metabolomic fingerprinting is based on multiple
      spectrometric and chromatographic signals, used either alone or combined with
      structural and chemical information of metabolic markers at the qualitative and
      semiquantitative level. However, signal shifting, convolution, and matrix effects
      may compromise metabolomic patterns. Recent increase in the use of qualitative
      metabolomic data, described by the presence (1) or absence (0) of particular
      metabolites, demonstrates great potential in the field of metabolomic profiling
      and fingerprint analysis. Objectives: The aim of this study is a comprehensive
      evaluation of binary similarity measures for the elucidation of patterns among
      samples of different botanical origin and various metabolomic profiles. Methods:
      Nine qualitative metabolomic data sets covering a wide range of natural products
      and metabolomic profiles were applied to assess 44 binary similarity measures for
      the fingerprinting of plant extracts and natural products. The measures were
      analyzed by the novel sum of ranking differences method (SRD), searching for the
      most promising candidates. Results: Baroni-Urbani-Buser (BUB) and Hawkins-Dotson
      (HD) similarity coefficients were selected as the best measures by SRD and
      analysis of variance (ANOVA), while Dice (Di1), Yule, Russel-Rao, and Consonni
      Todeschini 3 ranked the worst. ANOVA revealed that concordantly and
      intermediately symmetric similarity coefficients are better candidates for
      metabolomic fingerprinting than the asymmetric and correlation based ones. The
      fingerprint analysis based on the BUB and HD coefficients and qualitative
      metabolomic data performed equally well as the quantitative metabolomic profile
      analysis. Conclusion: Fingerprint analysis based on the qualitative metabolomic
      profiles and binary similarity measures proved to be a reliable way in finding
      the same/similar patterns in metabolomic data as that extracted from quantitative
      data.

PMID- 29568244
TI  - Herbal medicine for sports: a review.
AB  - The use of herbal medicinal products and supplements has increased during last
      decades. At present, some herbs are used to enhance muscle strength and body
      mass. Emergent evidence suggests that the health benefits from plants are
      attributed to their bioactive compounds such as Polyphenols, Terpenoids, and
      Alkaloids which have several physiological effects on the human body. At times,
      manufacturers launch numerous products with banned ingredient inside with
      inappropriate amounts or fake supplement inducing harmful side effect.
      Unfortunately up to date, there is no guarantee that herbal supplements are safe
      for anyone to use and it has not helped to clear the confusion surrounding the
      herbal use in sport field especially. Hence, the purpose of this review is to
      provide guidance on the efficacy and side effect of most used plants in sport. We
      have identified plants according to the following categories: Ginseng, alkaloids,
      and other purported herbal ergogenics such as Tribulus Terrestris, Cordyceps
      Sinensis. We found that most herbal supplement effects are likely due to
      activation of the central nervous system via stimulation of catecholamines.
      Ginseng was used as an endurance performance enhancer, while alkaloids
      supplementation resulted in improvements in sprint and cycling intense exercises.
      Despite it is prohibited, small amount of ephedrine was usually used in
      combination with caffeine to enhance muscle strength in trained individuals. Some
      other alkaloids such as green tea extracts have been used to improve body mass
      and composition in athletes. Other herb (i.e. Rhodiola, Astragalus) help relieve
      muscle and joint pain, but results about their effects on exercise performance
      are missing.

PMID- 29568247
TI  - Diabetes Type 2 and Pancreatic Cancer: A History Unfolding.
AB  - Pancreatic Cancer is the fourth cause of cancer-related deaths in the United
      States. Up to 80% of pancreatic cancer patients present with either new-onset
      type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent
      literature suggests that diabetes mellitus type 2 is a risk factor, a
      manifestation and a prognostic factor for pancreatic cancer. This article is
      intended to clarify the evidence about diabetes as a risk factor for pancreatic
      cancer.

PMID- 29568249
TI  - Challenges of pheromone-based mating disruption of Cydia strobilella and
      Dioryctria abietella in spruce seed orchards.
AB  - Seed orchards function as the primary source of high-quality seeds for
      reforestation in many European countries, but their seed yields can be severely
      reduced due to seed- and cone-feeding insects. We evaluated various parameters of
      pheromone-based mating disruption for control of the moths Cydia strobilella and
      Dioryctria abietella, which are major pests in European Picea abies seed
      orchards. We applied different types of pheromone dispensers (rubber septa or wax
      droplets) at different densities and heights, and with different amounts of
      active components, covering whole orchards or part of an orchard. The efficacy of
      the treatment was evaluated by analysing male captures in pheromone-baited
      assessment traps, and presence of larvae in cones. A dramatic decrease (94-100%)
      in capture of males in traps occurred in all pheromone-treated plots compared to
      control plots for both moth species. In contrast, a subsequent reduction in
      larval numbers in cones was only achieved when wax droplets were used as the
      dispensing formulation at high density and at the highest pheromone dose tested,
      and only in half of the trials for each pest species. Electrophysiological
      recordings using antennae of male C. strobilella indicated elevated pheromone
      concentrations in a treated plot versus a control plot. Our results show that
      mating disruption has potential to reduce cone damage in spruce seed orchards
      caused by C. strobilella and D. abietella, but optimisation of the technique is
      required to achieve consistent and efficient population suppression of these
      pests.

PMID- 29568248
TI  - Sterile insect technique and Wolbachia symbiosis as potential tools for the
      control of the invasive species Drosophila suzukii.
AB  - Drosophila suzukii, a vinegar fly originated from Southeast Asia, has recently
      invaded western countries, and it has been recognized as an important threat of a
      wide variety of several commercial soft fruits. This review summarizes the
      current information about the biology and dispersal of D. suzukii and discusses
      the current status and prospects of control methods for the management of this
      pest. We highlight current knowledge and ongoing research on innovative
      environmental-friendly control methods with emphasis on the sterile insect
      technique (SIT) and the incompatible insect technique (IIT). SIT has been
      successfully used for the containment, suppression or even eradication of
      populations of insect pests. IIT has been proposed as a stand-alone tool or in
      conjunction with SIT for insect pest control. The principles of SIT and IIT are
      reviewed, and the potential value of each approach in the management of D.
      suzukii is analyzed. We thoroughly address the challenges of SIT and IIT, and we
      propose the use of SIT as a component of an area-wide integrated pest management
      approach to suppress D. suzukii populations. As a contingency plan, we suggest a
      promising alternative avenue through the combination of these two techniques,
      SIT/IIT, which has been developed and is currently being tested in open-field
      trials against Aedes mosquito populations. All the potential limiting factors
      that may render these methods ineffective, as well as the requirements that need
      to be fulfilled before their application, are discussed.

PMID- 29568250
TI  - Dietary yeast affects preference and performance in Drosophila suzukii.
AB  - Yeasts play an important role in nutrition physiology and host attraction of many
      Drosophila species, and associations with various yeast species are documented
      for several drosophilid flies. The pest Drosophila suzukii (Matsumura) has a
      predominant association with the yeast Hanseniaspora uvarum. However, research
      has not been conducted on the nutritional physiology of the yeasts associated
      with D. suzukii (spotted wing drosophila). Therefore, in this study, we
      determined whether dietary yeast was nutritionally relevant and whether yeast
      species closely associated with D. suzukii positively affected life-history
      traits. Our results confirm a crucial role of dietary yeast in the larval
      development and survival of D. suzukii. Furthermore, we found specific effects of
      the closely associated yeast species H. uvarum and Candida sp. on larval
      survival. Observations of the egg-laying behaviour of D. suzukii on cherry fruits
      artificially colonised with different yeast species revealed that the number of
      eggs laid increased on fruits colonised with Candida sp. and Saccharomyces
      cerevisiae.

PMID- 29568251
TI  - Infection of Drosophila suzukii with the obligate insect-pathogenic fungus
      Entomophthora muscae.
AB  - Physiological constraints restrict specialist pathogens from infecting new hosts.
      From an applied perspective, a narrow host range makes specialist pathogens
      interesting for targeting specific pest insects since they have minimal direct
      effects on non-target species. Entomopathogenic fungi of the genus Entomophthora
      are dipteran-specific but have not been investigated for their ability to infect
      the spotted wing drosophila (SWD; Drosophila suzukii) a fruit-damaging pest
      invasive to Europe and America. Our main goal was to study whether SWD is in the
      physiological host range of the entomophthoralean species E. muscae. We
      investigated pathogenicity and virulence of E. muscae towards its main natural
      host, the housefly Musca domestica, and towards SWD. We found that E. muscae
      readily infected and significantly reduced survival of SWD by 27.3% with the
      majority of flies dying 4-8 days post-exposure. In comparison with SWD, infection
      of the natural host M. domestica resulted in an even higher mortality of 62.9%
      and larger conidial spores of E. muscae, reflecting the physiological constraints
      of the pathogen in the atypical host. We demonstrated that pathogens of the E.
      muscae species complex that typically have a narrow natural host range of one or
      few dipteran species are able to infect SWD, and we described a new method for in
      vivo transmission and infection of an entomophthoralean fungus to SWD.

PMID- 29568252
TI  - Insect pathogenic fungi and bed bugs: behaviour, horizontal transfer and the
      potential contribution to IPM solutions.
AB  - The increasing problem of bed bugs requires the development of new control
      strategies, and insect pathogenic fungi can contribute towards management. We
      used laboratory bioassays with Isaria fumosoroseus, Lecanicillium muscarium and
      Beauveria bassiana to evaluate their virulence to the bed bug. Only B. bassiana
      significantly affected bed bug survival and was dependent on dose and
      formulation. A 2% B. bassiana oil formulation induced horizontal transfer to
      elevate mortality in a 10-day arena bioassay. Temporal distribution of contagious
      individuals and increasing the dose from 2 to 4% did not increase mortality.
      Horizontal transfer mainly occurred between adults, and only partly between
      adults and nymphs. Bed bugs showed activity peaks during the night, and activity
      was increased by elevated levels of CO2. Distribution between harbourages was not
      affected by CO2 activation, level of infection or the bio-pesticide, and
      horizontal transfer was not dependent on the degree of aggregation. Movement in
      the arenas negatively affected horizontal transfer when the number of susceptible
      individuals was large. Level of infection also influenced behaviour as the bed
      bug movement increased with elevated disease burden. The use of fungi as a part
      of an integrated pest management strategy seems to be an interesting option that
      should be investigated further. B. bassiana kills bed bugs and can be carried to
      harbourages to target hidden individuals.

PMID- 29568253
TI  - Feasibility and safety of total laparoscopic hysterectomy for huge uteri without
      the use of uterine manipulator: description of emblematic cases.
AB  - Background: Uterine manipulator is a very useful tool in performing total
      laparoscopic hysterectomy (TLH) for large uteri; however, in some cases, it
      cannot be used due to unfavorable anatomical conditions. The feasibility and
      safety of TLH for very large uteri without the use of uterine manipulator has not
      yet been established. Results: We describe two emblematic cases of TLH for huge
      fibromatous uteri: the first one for a uterus weighing 5700 g, which is the
      largest uterus laparoscopically removed to date reported in literature, and the
      second one for a uterus of 3670 g associated with a severe lymph node neoplastic
      disease.In both cases, TLH was successfully and safely performed even without the
      use of uterine manipulator, thus allowing a rapid recovery, especially in the
      second case, which was essential for a fast start of the most appropriate
      oncological treatment, the best quality of life and undoubtedly cosmetic
      advantages. Conclusions: Although we believe in the great usefulness of the
      uterine manipulator in performing TLH for huge uteri, in the present paper, we
      demonstrate the feasibility and safety of such complex surgery also when the use
      of this tool is not possible due to unfavorable anatomical condition.

PMID- 29568254
TI  - Implementation of laparoscopic hysterectomy for endometrial cancer over the past
      decade.
AB  - Background: Laparoscopic hysterectomy (LH) for the treatment of early-stage
      endometrial carcinoma/cancer (EC) has demonstrated to be safe in several
      randomized controlled trials. Yet, data on implementation of LH in clinical
      practice are limited. In the present study, implementation of LH for EC was
      evaluated in a large oncology network in the Netherlands. Results:
      Retrospectively, a total of 556 EC patients with FIGO stage I-II were registered
      in the selected years. The proportion of LH gradually increased from 11% in 2006
      to 85% in 2015. LH was more often performed in patients with low-grade EC and was
      not related to the studied patient characteristics. The introduction of TLH was
      frequently preceded by LAVH. Patients treated in teaching hospitals were more
      likely to undergo a LH compared to patients in non-teaching hospitals. The
      conversion rate was 7.7%, and the overall complication rates between LH and AH
      were comparable, but less postoperative complications in LH. Conclusions:
      Implementation of laparoscopic hysterectomy for early-stage EC increased from 11
      to 85% in 10 years. Implementation of TLH was often preceded by LAVH and was
      faster in teaching hospitals.

PMID- 29568255
TI  - Oligosaccharide model of the vascular endothelial glycocalyx in physiological
      flow.
AB  - Experiments have consistently revealed the pivotal role of the endothelial
      glycocalyx layer in vasoregulation and the layer's contribution to
      mechanotransduction pathways. However, the exact mechanism by which the
      glycocalyx mediates fluid shear stress remains elusive. This study employs atomic
      scale molecular simulations with the aim of investigating the conformational and
      orientation properties of highly flexible oligosaccharide components of the
      glycocalyx and their suitability as transduction molecules under hydrodynamic
      loading. Fluid flow was shown to have nearly no effect on the conformation
      populations explored by the oligosaccharide, in comparison with static
      (diffusion) conditions. However, the glycan exhibited a significant orientation
      change, when compared to simple diffusion, aligning itself with the flow
      direction. It is the tethered end of the glycan, an asparagine amino acid, which
      experienced conformational changes as a result of this flow-induced bias. Our
      results suggest that shear flow through the layer can have an impact on the
      conformational properties of saccharide-decorated transmembrane proteins, thus
      acting as a mechanosensor.

PMID- 29568256
TI  - Space-time structure and wavevector anisotropy in space plasma turbulence.
AB  - Space and astrophysical plasmas often develop into a turbulent state and exhibit
      nearly random and stochastic motions. While earlier studies emphasize more on
      understanding the energy spectrum of turbulence in the one-dimensional context
      (either in the frequency or the wavenumber domain), recent achievements in plasma
      turbulence studies provide an increasing amount of evidence that plasma
      turbulence is essentially a spatially and temporally evolving phenomenon. This
      review presents various models for the space-time structure and anisotropy of the
      turbulent fields in space plasmas, or equivalently the energy spectra in the
      wavenumber-frequency domain for the space-time structures and that in the
      wavevector domain for the anisotropies. The turbulence energy spectra are
      evaluated in different one-dimensional spectral domains; one speaks of the
      frequency spectra in the spacecraft observations and the wavenumber spectra in
      the numerical simulation studies. The notion of the wavenumber-frequency spectrum
      offers a more comprehensive picture of the turbulent fields, and good models can
      explain the one-dimensional spectra in the both domains at the same time. To
      achieve this goal, the Doppler shift, the Doppler broadening, linear-mode
      dispersion relations, and sideband waves are reviewed. The energy spectra are
      then extended to the wavevector domain spanning the directions parallel and
      perpendicular to the large-scale magnetic field. By doing so, the change in the
      spectral index at different projections onto the one-dimensional spectral domain
      can be explained in a simpler way.

PMID- 29568257
TI  - Characterization of Diffusion Metric Map Similarity in Data From a Clinical Data
      Repository Using Histogram Distances.
AB  - As the sharing of data is mandated by funding agencies and journals, reuse of
      data has become more prevalent. It becomes imperative, therefore, to develop
      methods to characterize the similarity of data. While users can group data based
      on the acquisition parameters stored in the file headers, these gives no
      indication whether a file can be combined with other data without increasing the
      variance in the data set. Methods have been implemented that characterize the
      signal-to-noise ratio or identify signal drop-outs in the raw image files, but
      potential users of data often have access to calculated metric maps and these are
      more difficult to characterize and compare. Here we describe a histogram-distance
      based method applied to diffusion metric maps of fractional anisotropy and mean
      diffusivity that were generated using data extracted from a repository of
      clinically-acquired MRI data. We describe the generation of the data set, the
      pitfalls specific to diffusion MRI data, and the results of the histogram
      distance analysis. We find that, in general, data from GE scanners are less
      similar than are data from Siemens scanners. We also find that the distribution
      of distance metric values is not Gaussian at any selection of the acquisition
      parameters considered here (field strength, number of gradient directions, b
      value, and vendor).

PMID- 29568258
TI  - Using a Double-Coil TMS Protocol to Assess Preparatory Inhibition Bilaterally.
AB  - Transcranial magnetic stimulation (TMS) applied over the primary motor cortex
      (M1), elicits motor-evoked potentials (MEPs) in contralateral limb muscles which
      are valuable indicators of corticospinal excitability (CSE) at the time of
      stimulation. So far, most studies have used single-coil TMS over one M1, yielding
      MEPs in muscles of a single limb-usually the hand. However, tracking CSE in the
      two hands simultaneously would be useful in many contexts. We recently showed
      that, in the resting state, double-coil stimulation of the two M1 with a 1 ms
      inter-pulse interval (double-coil1 ms TMS) elicits MEPs in both hands that are
      comparable to MEPs obtained using single-coil TMS. To further evaluate this new
      technique, we considered the MEPs elicited by double-coil1 ms TMS in an
      instructed-delay choice reaction time task where a prepared response has to be
      withheld until an imperative signal is displayed. Single-coil TMS studies have
      repetitively shown that in this type of task, the motor system is transiently
      inhibited during the delay period, as evident from the broad suppression of MEP
      amplitudes. Here, we aimed at investigating whether a comparable inhibitory
      effect can be observed with MEPs elicited using double-coil1 ms TMS. To do so, we
      compared the amplitude as well as the coefficient of variation (CV) of MEPs
      produced by double-coil1 ms or single-coil TMS during action preparation. We
      observed that MEPs were suppressed (smaller amplitude) and often less variable
      (smaller CV) during the delay period compared to baseline. Importantly, these
      effects were equivalent whether single-coil or double-coil1 ms TMS was used. This
      suggests that double-coil1 ms TMS is a reliable tool to assess CSE, not only when
      subjects are at rest, but also when they are involved in a task, opening new
      research horizons for scientists interested in the corticospinal correlates of
      human behavior.

PMID- 29568259
TI  - Auditory Proprioceptive Integration: Effects of Real-Time Kinematic Auditory
      Feedback on Knee Proprioception.
AB  - The purpose of the study was to assess the influence of real-time auditory
      feedback on knee proprioception. Thirty healthy participants were randomly
      allocated to control (n = 15), and experimental group I (15). The participants
      performed an active knee-repositioning task using their dominant leg,
      with/without additional real-time auditory feedback where the frequency was
      mapped in a convergent manner to two different target angles (40 and 75 degrees
      ). Statistical analysis revealed significant enhancement in knee re-positioning
      accuracy for the constant and absolute error with real-time auditory feedback,
      within and across the groups. Besides this convergent condition, we established a
      second divergent condition. Here, a step-wise transposition of frequency was
      performed to explore whether a systematic tuning between auditory-proprioceptive
      repositioning exists. No significant effects were identified in this divergent
      auditory feedback condition. An additional experimental group II (n = 20) was
      further included. Here, we investigated the influence of a larger magnitude and
      directional change of step-wise transposition of the frequency. In a first step,
      results confirm the findings of experiment I. Moreover, significant effects on
      knee auditory-proprioception repositioning were evident when divergent auditory
      feedback was applied. During the step-wise transposition participants showed
      systematic modulation of knee movements in the opposite direction of
      transposition. We confirm that knee re-positioning accuracy can be enhanced with
      concurrent application of real-time auditory feedback and that knee re
      positioning can modulated in a goal-directed manner with step-wise transposition
      of frequency. Clinical implications are discussed with respect to joint position
      sense in rehabilitation settings.

PMID- 29568260
TI  - Event-Related Potential Responses to Task Switching Are Sensitive to Choice of
      Spatial Filter.
AB  - Event-related potential (ERP) studies using the task-switching paradigm show that
      multiple ERP components are modulated by activation of proactive control
      processes involved in preparing to repeat or switch task and reactive control
      processes involved in implementation of the current or new task. Our
      understanding of the functional significance of these ERP components has been
      hampered by variability in their robustness, as well as their temporal and scalp
      distribution across studies. The aim of this study is to examine the effect of
      choice of reference electrode or spatial filter on the number, timing and scalp
      distribution of ERP elicited during task-switching. We compared four
      configurations, including the two most common (i.e., average mastoid reference
      and common average reference) and two novel ones that aim to reduce volume
      conduction (i.e., reference electrode standardization technique (REST) and
      surface Laplacian) on mixing cost and switch cost effects in cue-locked and
      target-locked ERP waveforms in 201 healthy participants. All four spatial filters
      showed the same well-characterized ERP components that are typically seen in task
      switching paradigms: the cue-locked switch positivity and target-locked N2/P3
      effect. However, both the number of ERP effects associated with mixing and switch
      cost, and their temporal and spatial resolution were greater with the surface
      Laplacian transformation which revealed rapid temporal adjustments that were not
      identifiable with other spatial filters. We conclude that the surface Laplacian
      transformation may be more suited to characterize EEG signatures of complex
      spatiotemporal networks involved in cognitive control.

PMID- 29568261
TI  - 8-O-Acetyl Shanzhiside Methylester From Lamiophlomis Rotata Reduces Neuropathic
      Pain by Inhibiting the ERK/TNF-alpha Pathway in Spinal Astrocytes.
AB  - Lamiophlomis rotata (L. rotata; Benth.) Kudo is an effective traditional herb in
      the clinical treatment of chronic pain syndromes in China. 8-O-acetyl shanzhiside
      methylester (8-OaS), a chief component in L. rotata, possesses potent
      immunosuppressive activities and favorable analgesic effects. This study was
      proposed to compare the analgesic effects of 8-OaS with those of lidocaine and
      ketamine in a spinal nerve ligation (SNL) model by behavioral tests, and then
      investigated its effects upon the expression of spinal glial fibrillary acidic
      protein (GFAP), phosphorylated extracellular regulated protein kinases (pERK) and
      tumor necrosis factor-alpha (TNF-alpha) via immunofluorescence staining and
      western blot analyses. The data showed consecutive intrathecal injection of 8-OaS
      for 2 weeks brought about remarkable palliation of neuropathic pain (NP),
      possessing similar anti-allodynia effects with those of lidocaine and ketamine.
      Two weeks after surgery, pERK within the spinal dorsal horn was mainly expressed
      in astrocytes more than neurons and microglia, and 8-OaS inhibited spinal
      astrocytic activation and TNF-alpha expression. Finally, co-treatment of 8-OaS
      and PD98059 (an Extracellular signal-regulated kinase, ERK inhibitor) did not
      lead to remarkable increase in pain relief or TNF-alpha expression comparing to
      rats treated with 8-OaS or PD98059 alone. In conclusion, the anti-nociceptive
      effects of 8-OaS in the condition of NP relied on the inhibition of SNL-induced
      astrocyte activation, probably via the down-regulation of the ERK/TNF-alpha
      pathway.

PMID- 29568263
TI  - Neuroanatomy from Mesoscopic to Nanoscopic Scales: An Improved Method for the
      Observation of Semithin Sections by High-Resolution Scanning Electron Microscopy.
AB  - Semithin sections are commonly used to examine large areas of tissue with an
      optical microscope, in order to locate and trim the regions that will later be
      studied with the electron microscope. Ideally, the observation of semithin
      sections would be from mesoscopic to nanoscopic scales directly, instead of using
      light microscopy and then electron microscopy (EM). Here we propose a method that
      makes it possible to obtain high-resolution scanning EM images of large areas of
      the brain in the millimeter to nanometer range. Since our method is compatible
      with light microscopy, it is also feasible to generate hybrid light and electron
      microscopic maps. Additionally, the same tissue blocks that have been used to
      obtain semithin sections can later be used, if necessary, for transmission EM, or
      for focused ion beam milling and scanning electron microscopy (FIB-SEM).

PMID- 29568262
TI  - Dynamical Mechanism of Hyperpolarization-Activated Non-specific Cation Current
      Induced Resonance and Spike-Timing Precision in a Neuronal Model.
AB  - Hyperpolarization-activated cyclic nucleotide-gated cation current (Ih ) plays
      important roles in the achievement of many physiological/pathological functions
      in the nervous system by modulating the electrophysiological activities, such as
      the rebound (spike) to hyperpolarization stimulations, subthreshold membrane
      resonance to sinusoidal currents, and spike-timing precision to stochastic
      factors. In the present paper, with increasing gh (conductance of Ih ), the
      rebound (spike) and subthreshold resonance appear and become stronger, and the
      variability of the interspike intervals (ISIs) becomes lower, i.e., the
      enhancement of spike-timing precision, which are simulated in a conductance-based
      theoretical model and well explained by the nonlinear concept of bifurcation.
      With increasing gh , the stable node to stable focus, to coexistence behavior,
      and to firing via the codimension-1 bifurcations (Hopf bifurcation, saddle-node
      bifurcation, saddle-node bifurcations on an invariant circle, and saddle
      homoclinic orbit) and codimension-2 bifurcations such as Bogdanov-Takens (BT)
      point related to the transition between saddle-node and Hopf bifurcations, are
      acquired with 1- and 2-parameter bifurcation analysis. The decrease of
      variability of ISIs with increasing gh is induced by the fast decrease of the
      standard deviation of ISIs, which is related to the increase of the capacity of
      resisting noisy disturbance due to the firing becomes far away from the
      bifurcation point. The enhancement of the rebound (spike) with increasing gh
      builds up a relationship to the decrease of the capacity of resisting disturbance
      like the hyperpolarization stimulus as the resting state approaches the
      bifurcation point. The "typical"-resonance and non-resonance appear in the
      parameter region of the stable focus and node far away from the bifurcation
      points, respectively. The complex or "strange" dynamics, such as the "weak"
      resonance for the stable node near the transition point between the stable node
      and focus and the non-resonance for the stable focus close to the codimension-1
      and -2 bifurcation points, are discussed.

PMID- 29568264
TI  - Lose-Shift Responding in Humans Is Promoted by Increased Cognitive Load.
AB  - The propensity of animals to shift choices immediately after unexpectedly poor
      reinforcement outcomes is a pervasive strategy across species and tasks. We
      report here on the memory supporting such lose-shift responding in humans,
      assessed using a binary choice task in which random responding is the optimal
      strategy. Participants exhibited little lose-shift responding when fully
      attending to the task, but this increased by 30%-40% in participants that
      performed with additional cognitive load that is known to tax executive systems.
      Lose-shift responding in the cognitively loaded adults persisted throughout the
      testing session, despite being a sub-optimal strategy, but was less likely as the
      time increased between reinforcement and the subsequent choice. Furthermore,
      children (5-9 years old) without load performed similarly to the cognitively
      loaded adults. This effect disappeared in older children aged 11-13 years old.
      These data provide evidence supporting our hypothesis that lose-shift responding
      is a default and reflexive strategy in the mammalian brain, likely mediated by a
      decaying memory trace, and is normally suppressed by executive systems. Reducing
      the efficacy of executive control by cognitive load (adults) or underdevelopment
      (children) increases its prevalence. It may therefore be an important component
      to consider when interpreting choice data, and may serve as an objective
      behavioral assay of executive function in humans that is easy to measure.

PMID- 29568266
TI  - Normalization of Blood Pressure With Spinal Cord Epidural Stimulation After
      Severe Spinal Cord Injury.
AB  - Chronic low blood pressure and orthostatic hypotension remain challenging
      clinical issues after severe spinal cord injury (SCI), affecting health,
      rehabilitation, and quality of life. We previously reported that targeted
      lumbosacral spinal cord epidural stimulation (scES) could promote stand and step
      functions and restore voluntary movement in patients with chronic motor complete
      SCI. This study addresses the effects of targeted scES for cardiovascular
      function (CV-scES) in individuals with severe SCI who suffer from chronic
      hypotension. We tested the hypothesis that CV-scES can increase resting blood
      pressure and attenuate chronic hypotension in individuals with chronic cervical
      SCI. Four research participants with chronic cervical SCI received an implant of
      a 16-electrode array on the dura (L1-S1 cord segments, T11-L1 vertebrae).
      Individual-specific CV-scES configurations (anode and cathode electrode
      selection, voltage, frequency, and pulse width) were identified to maintain
      systolic blood pressure within targeted normative ranges without skeletal muscle
      activity of the lower extremities as assessed by electromyography. These
      individuals completed five 2-h sessions using CV-scES in an upright, seated
      position during measurement of blood pressure and heart rate. Noninvasive
      continuous blood pressure was measured from a finger cuff by plethysmograph
      technique. For each research participant there were statistically significant
      increases in mean arterial pressure in response to CV-scES that was maintained
      within normative ranges. This result was reproducible over the five sessions with
      concomitant decreases or no changes in heart rate using individual-specific CV
      scES that was modulated with modest amplitude changes throughout the session. Our
      study shows that stimulating dorsal lumbosacral spinal cord can effectively and
      safely activate mechanisms to elevate blood pressures to normal ranges from a
      chronic hypotensive state in humans with severe SCI with individual-specific CV
      scES.

PMID- 29568265
TI  - Explicit Performance in Girls and Implicit Processing in Boys: A Simultaneous
      fNIRS-ERP Study on Second Language Syntactic Learning in Young Adolescents.
AB  - Learning a second language (L2) proceeds with individual approaches to
      proficiency in the language. Individual differences including sex, as well as
      working memory (WM) function appear to have strong effects on behavioral
      performance and cortical responses in L2 processing. Thus, by considering sex and
      WM capacity, we examined neural responses during L2 sentence processing as a
      function of L2 proficiency in young adolescents. In behavioral tests, girls
      significantly outperformed boys in L2 tests assessing proficiency and grammatical
      knowledge, and in a reading span test (RST) assessing WM capacity. Girls, but not
      boys, showed significant correlations between L2 tests and RST scores. Using
      functional near-infrared spectroscopy (fNIRS) and event-related potential (ERP)
      simultaneously, we measured cortical responses while participants listened to
      syntactically correct and incorrect sentences. ERP data revealed a grammaticality
      effect only in boys in the early time window (100-300 ms), implicated in phrase
      structure processing. In fNIRS data, while boys had significantly increased
      activation in the left prefrontal region implicated in syntactic processing,
      girls had increased activation in the posterior language-related region involved
      in phonology, semantics, and sentence processing with proficiency. Presumably,
      boys implicitly focused on rule-based syntactic processing, whereas girls made
      full use of linguistic knowledge and WM function. The present results provide
      important fundamental data for learning and teaching in L2 education.

PMID- 29568267
TI  - Performance of an Ambulatory Dry-EEG Device for Auditory Closed-Loop Stimulation
      of Sleep Slow Oscillations in the Home Environment.
AB  - Recent research has shown that auditory closed-loop stimulation can enhance sleep
      slow oscillations (SO) to improve N3 sleep quality and cognition. Previous
      studies have been conducted in lab environments. The present study aimed to
      validate and assess the performance of a novel ambulatory wireless dry-EEG device
      (WDD), for auditory closed-loop stimulation of SO during N3 sleep at home. The
      performance of the WDD to detect N3 sleep automatically and to send auditory
      closed-loop stimulation on SO were tested on 20 young healthy subjects who slept
      with both the WDD and a miniaturized polysomnography (part 1) in both stimulated
      and sham nights within a double blind, randomized and crossover design. The
      effects of auditory closed-loop stimulation on delta power increase were assessed
      after one and 10 nights of stimulation on an observational pilot study in the
      home environment including 90 middle-aged subjects (part 2).The first part, aimed
      at assessing the quality of the WDD as compared to a polysomnograph, showed that
      the sensitivity and specificity to automatically detect N3 sleep in real-time
      were 0.70 and 0.90, respectively. The stimulation accuracy of the SO ascending
      phase targeting was 45 +/- 52 degrees . The second part of the study, conducted
      in the home environment, showed that the stimulation protocol induced an increase
      of 43.9% of delta power in the 4 s window following the first stimulation
      (including evoked potentials and SO entrainment effect). The increase of SO
      response to auditory stimulation remained at the same level after 10 consecutive
      nights. The WDD shows good performances to automatically detect in real-time N3
      sleep and to send auditory closed-loop stimulation on SO accurately. These
      stimulation increased the SO amplitude during N3 sleep without any adaptation
      effect after 10 consecutive nights. This tool provides new perspectives to figure
      out novel sleep EEG biomarkers in longitudinal studies and can be interesting to
      conduct broad studies on the effects of auditory stimulation during sleep.

PMID- 29568268
TI  - Synergistic Effect on Neurodegeneration by N-Truncated Abeta4-42 and
      Pyroglutamate Abeta3-42 in a Mouse Model of Alzheimer's Disease.
AB  - The N-terminally truncated pyroglutamate Abeta3-42 (AbetapE3-42) and Abeta4-42
      peptides are known to be highly abundant in the brain of Alzheimer's disease (AD)
      patients. Both peptides show enhanced aggregation and neurotoxicity in comparison
      to full-length Abeta, suggesting that these amyloid peptides may play an
      important role in the pathogenesis of AD. The aim of the present work was to
      study the direct effect of the combination of AbetapE3-42 and Abeta4-42 on
      ongoing AD-related neuron loss, pathology, and neurological deficits in
      transgenic mice. Bigenic mice were generated by crossing the established TBA42
      and Tg4-42 mouse models expressing the N-truncated Abeta peptides AbetapE3-42 and
      Abeta4-42, respectively. After generation of the bigenic mice, detailed
      phenotypical characterization was performed using either immunostainings to
      evaluate amyloid pathology or quantification of neuron numbers using design-based
      stereology. The elevated plus maze was used to study anxiety levels. In order to
      evaluate sensori-motor deficits, the inverted grid, the balance beam and the
      string suspension tasks were applied. We could demonstrate that co-expression of
      AbetapE3-42 and Abeta4-42 accelerates neuron loss in the CA1 pyramidal layer of
      young bigenic mice as seen by reduced neuron numbers in comparison to single
      transgenic homozygous mice expressing either AbetapE3-42 or Abeta4-42. This
      observation coincides with the robust intraneuronal Abeta accumulation observed
      in the bigenic mice. In addition, loss of anxiety and motor deficits were
      enhanced in an age-dependent manner. The sensori-motor deficits correlate with
      the abundant spinal cord pathology, as demonstrated by robust intracellular Abeta
      accumulation within motor neurons and extracellular Abeta deposition. Our
      observations demonstrate that a combination of AbetapE3-42 and Abeta4-42 has a
      stronger effect on ongoing AD pathology than the peptides alone. Therefore,
      AbetapE3-42 and Abeta4-42 might represent excellent potential therapeutic targets
      and diagnostic markers for AD.

PMID- 29568269
TI  - cAMP Catalyzing Phosphodiesterases Control Cholinergic Muscular Activity But
      Their Inhibition Does Not Enhance 5-HT4 Receptor-Mediated Facilitation of
      Cholinergic Contractions in the Murine Gastrointestinal Tract.
AB  - Background: As the signal transduction of 5-HT4 receptors on cholinergic neurons
      innervating smooth muscle is controlled by phosphodiesterase (PDE) 4 in porcine
      stomach and colon, and human large intestine, the in vivo gastroprokinetic
      effects of a 5-HT4 receptor agonist might be enhanced by combination with a
      selective PDE4 inhibitor. The presence of 5-HT4 receptors on cholinergic neurons
      towards murine gastrointestinal circular muscle was recently shown. If the
      control of this receptor pathway by PDE4 is also present in mice, this might be a
      good model for in vivo testing of the combination therapy. Therefore this study
      investigates the role of cAMP catalyzing PDEs in smooth muscle cell activity and
      in the intraneuronal signal transduction of the 5-HT4 receptors in the
      gastrointestinal tract of C57Bl/6J mice. Methods: In circular smooth muscle
      strips from murine fundus, jejunum, and colon, submaximal cholinergic
      contractions were induced by either electrical field stimulation (EFS) or by
      carbachol (muscarinic receptor agonist). The influence of the PDE inhibitors IBMX
      (non-selective), vinpocetine (PDE1), EHNA (PDE2), cilostamide (PDE3), and
      rolipram (PDE4) was tested on these contractions and on the facilitating effect
      of a submaximal concentration of prucalopride (5-HT4 receptor agonist) on EFS
      induced contractions. Results: In the three gastrointestinal regions, IBMX and
      cilostamide concentration-dependently decreased carbachol- as well as EFS-induced
      contractions. Some inhibitory effect was also observed with rolipram. In the
      fundus a non-significant trend for an enhancement of the facilitating effect of
      prucalopride on EFS-induced contractions was observed with IBMX, but none of the
      selective PDE inhibitors enhanced the facilitating effect of prucalopride in
      fundus, jejunum or colon. Conclusion: In analogy with the porcine
      gastrointestinal tract, in murine fundus, jejunum, and colon circular smooth
      muscle PDE3 is the main regulator of the cAMP turnover, with some contribution of
      PDE4. In contrast to the porcine gastrointestinal tract, the in vitro
      facilitation of electrically induced cholinergic contractions by 5-HT4 receptor
      stimulation could not be enhanced by specific PDE inhibition. The C57Bl/6J murine
      model is thus not suitable for in vivo testing of a 5-HT4 receptor agonist
      combined with a selective PDE4 inhibitor.

PMID- 29568271
TI  - End-of-Fiber Signals Strongly Influence the First and Second Phases of the M Wave
      in the Vastus Lateralis: Implications for the Study of Muscle Excitability.
AB  - It has been recurrently observed that, for compound muscle action potentials (M
      wave) recorded over the innervation zone of the vastus lateralis, the descending
      portion of the first phase generally shows an "inflection" or "shoulder." We
      sought to clarify the electrical origin of this shoulder-like feature and examine
      its implications. M waves evoked by maximal single shocks to the femoral nerve
      were recorded in monopolar and bipolar configurations from 126 individuals using
      classical (10-mm recording diameter, 20-mm inter-electrode distance) electrodes
      and from eight individuals using small electrodes arranged in a linear array. The
      changes of the M-wave waveform at different positions along the muscle fibers'
      direction were examined. The shoulder was identified more frequently in monopolar
      (97%) than in bipolar (46%) M waves. The shoulder of M waves recorded at
      different distances from the innervation zone had the same latency. Furthermore,
      the shoulder of the M wave recorded over the innervation zone coincided in
      latency with the positive peak of that recorded beyond the muscle. The positive
      phase of the M wave detected 20 mm away from the innervation zone was essentially
      composed of non-propagating components. The shoulder-like feature in monopolar
      and bipolar M waves results from the termination of action potentials at the
      superficial aponeurosis of the vastus lateralis. We conclude that, only the
      amplitude of the first phase, and not the second, of M waves recorded monopolarly
      and/or bipolarly in close proximity to the innervation zone can be used reliably
      to monitor possible changes in muscle membrane excitability.

PMID- 29568272
TI  - Four TRPM4 Cation Channel Mutations Found in Cardiac Conduction Diseases Lead to
      Altered Protein Stability.
AB  - Transient receptor potential melastatin member 4 (TRPM4), a non-selective cation
      channel, mediates cell membrane depolarization in immune response, insulin
      secretion, neurological disorders, and cancer. Pathological variants in TRPM4
      gene have been linked to several cardiac phenotypes such as complete heart block
      (CHB), ventricular tachycardia, and Brugada syndrome (BrS). Despite recent
      findings regarding the functional implications of TRPM4 in cardiac diseases, the
      molecular and cellular mechanisms leading to altered conduction are poorly
      understood. In the present study, we identify and characterize four novel TRPM4
      variants found in patients with CHB or ventricular fibrillation. Three of them,
      p.A101T, p.S1044C and a double variant p.A101T/P1204L, led to a decreased
      expression and function of the channel. On the contrary, the variant p.Q854R
      showed an increase in TRPM4 current. Recent evidence indicates that altered
      degradation rate of mutant proteins represents a pathogenic mechanism underlying
      genetic diseases. In consequence, protein turnover of WT-TRPM4 and TRPM4 variants
      overexpressed in HEK293 cells was analyzed using cycloheximide, an inhibitor of
      protein biosynthesis. Upon addition of cycloheximide, WT-TRPM4 decayed with a
      half-life of ~20 h, while loss-of-expression variants showed a ~30% increase in
      degradation rate, with a half-life close to 12 h. Together, the gain-of
      expression variant showed a higher stability and a doubled half-life compared to
      WT-TRPM4. In conclusion, decreased or increased protein expression of several
      TRPM4 variants linked to cardiac conduction disorders or ventricular arrhythmias
      were found to be caused by altered TRPM4 half-life compared to the WT form.

PMID- 29568270
TI  - Unifying Theories of Psychedelic Drug Effects.
AB  - How do psychedelic drugs produce their characteristic range of acute effects in
      perception, emotion, cognition, and sense of self? How do these effects relate to
      the clinical efficacy of psychedelic-assisted therapies? Efforts to understand
      psychedelic phenomena date back more than a century in Western science. In this
      article I review theories of psychedelic drug effects and highlight key concepts
      which have endured over the last 125 years of psychedelic science. First, I
      describe the subjective phenomenology of acute psychedelic effects using the best
      available data. Next, I review late 19th-century and early 20th-century theories
      model psychoses theory, filtration theory, and psychoanalytic theory-and
      highlight their shared features. I then briefly review recent findings on the
      neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I
      describe recent theories of psychedelic drug effects which leverage 21st-century
      cognitive neuroscience frameworks-entropic brain theory, integrated information
      theory, and predictive processing-and point out key shared features that link
      back to earlier theories. I identify an abstract principle which cuts across many
      theories past and present: psychedelic drugs perturb universal brain processes
      that normally serve to constrain neural systems central to perception, emotion,
      cognition, and sense of self. I conclude that making an explicit effort to
      investigate the principles and mechanisms of psychedelic drug effects is a
      uniquely powerful way to iteratively develop and test unifying theories of brain
      function.

PMID- 29568273
TI  - Regular Aerobic, Resistance, and Cross-Training Exercise Prevents Reduced
      Vascular Function Following a High Sugar or High Fat Mixed Meal in Young Healthy
      Adults.
AB  - The postprandial state can negatively influence flow mediated dilation (FMD), a
      predictor of atherosclerosis and cardiovascular disease. This investigation was
      designed to determine the effect of regular aerobic and/or resistance exercise on
      postprandial FMD after a high sugar or high fat mixed meal. Forty-five healthy
      participants were recruited from one of four groups: lean sedentary (SED),
      runners, weight lifters, and cross-trainers. Participants were randomly crossed
      over to a high sugar meal (HSM) and a high fat mixed meal (HFMM; both fat and
      carbohydrate). Pre-and postprandial endothelial function was assessed for both
      meals using brachial artery FMD. Plasma lipids, insulin, glucose, hs-CRP, and SOD
      were also measured with both meals. Endothelium-independent dilation was
      determined via sublingual nitroglycerin. Brachial artery FMD was reduced in SED
      following the HSM (9.9 +/- 0.9% at baseline, peak reduction at 60 min 6.5 +/-
      1.0%) and the HFMM (9.4 +/- 0.9% at baseline, peak reduction at 120 min 5.9 +/-
      1.2%; P < 0.05 for both, Mean +/- SEM). There was no change in FMD after either
      HSM or HFMM in runners, weight lifters, and cross-trainers. Post-prandial
      increases in blood glucose, insulin and triglycerides were less pronounced in the
      exercisers compared to SED. In addition, exercisers presented lower baseline
      plasma hs-CRP and higher SOD activity. Nitroglycerin responses were similar among
      groups. These results suggest that endothelial function is reduced in sedentary
      adults after a HSM or HFMM, but not in regular aerobic or resistance exercisers.
      This response may be due to favorable postprandial metabolic responses or lower
      postprandial levels of inflammation and oxidative stress. These findings may help
      to explain the cardioprotective effect of exercise.

PMID- 29568274
TI  - Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces
      Inflammation in High Fat Fed Mice With Hindlimb Ischemia.
AB  - Background: Fat deposition is associated with peripheral arterial disease.
      Adipose tissue has recently been implicated in vascular remodeling and angiogenic
      activity. We hypothesized that the transplantation of adipose tissues from normal
      mice improves blood flow perfusion and neovascularization in high-fat diet fed
      mice. Methods: After 14 weeks of high-fat diet (HFD)-fed mice, unilateral hind
      limb ischemia was performed. Subcutaneous white adipose tissue (WAT) and brown
      adipose tissue (BAT) fat pads were harvested from normal EGFP mice, and
      subcutaneously transplanted over the region of the adductor muscles of HFD mice.
      Blood flow was measured using Laser Doppler Scanner. Vascular density,
      macrophages infiltration, and macrophage polarization were examined by RT-qPCR,
      and immunohistochemistry. Results: We found that the transplantation of WAT
      derived from normal mice improved functional blood flow in HFD-fed mice compared
      to mice transplanted with BAT and sham-treated mice. WAT transplantation
      increased the recruitment of pericytes associated with nascent blood vessels, but
      did not affect capillary formation. Furthermore, transplantation of WAT
      ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the
      release of arteriogenic factors in ischemic muscles. Mice receiving WAT also
      displayed a marked reduction in several proinflammatory cytokines. In contrast,
      mice transplanted with BAT were glucose intolerant and demonstrated increased IL
      6 levels in ischemic muscles. Conclusion: These results indicate that
      transplantation of adipose tissue elicits improvements in blood perfusion and
      beneficial effects on systemic glucose homeostasis and could be a promising
      therapeutic option for the treatment of diabetic peripheral arterial disease.

PMID- 29568276
TI  - Effects of Continuing Oral Risperidone vs. Switching from Risperidone to
      Risperidone Long-Acting Injection on Cognitive Function in Stable Schizophrenia
      Patients: A Pilot Study.
AB  - Objectives: Risperidone is the first new generation antipsychotic drug to become
      available as a long-acting injection (LAI). The purpose of this study was to
      evaluate the effects of switching from oral risperidone to risperidone LAI (RLAI)
      on cognitive function in stable schizophrenia patients compared with the effects
      of continuing oral risperidone. Methods: Sixteen stable patients who had received
      risperidone monotherapy for at least 3 months were enrolled (the RLAI group).
      Before and 24 weeks after switching to RLAI, the Japanese-language version of the
      Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Positive and
      Negative Syndrome Scale (PANSS) were administered. To exclude the possibility of
      learning effects on the BACS-J results, 14 patients with stable schizophrenia who
      continued oral risperidone treatment were also assessed (the RIS group). Results:
      The two groups did not differ with respect to changes in the PANSS score, and no
      emergent side effects, including extrapyramidal symptoms, were observed. The BACS
      J score for verbal memory exhibited greater improvement in the RLAI group than in
      the RIS group (p = 0.047). Conclusion: The results of this preliminary study
      suggest that switching from oral risperidone to RLAI may improve verbal
      capability more than continuing with oral risperidone. However, these findings
      must be replicated in a larger, double-blind study.

PMID- 29568275
TI  - Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications.
AB  - Neurosteroids are a group of important endogenous molecules affecting many neural
      functions in the brain. Increasing evidence suggests a possible role of these
      neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other
      mental disorders. The aim of this review is to summarize the current knowledge
      about the neural functions of neurosteroids in the brain, and to evaluate the
      role of the key neurosteroids as candidate modulators in the etiology and
      therapeutics of SZ. The present paper provides a brief introduction of
      neurosteroid metabolism and distribution, followed by a discussion of the
      mechanisms underlying neurosteroid actions in the brain. The content regarding
      the modulation of the GABAA receptor is elaborated, given the considerable
      knowledge of its interactions with other neurotransmitter and neuroprotective
      systems, as well as its ameliorating effects on stress that may play a role in
      the SZ pathophysiology. In addition, several preclinical and clinical studies
      suggested a therapeutic benefit of neurosteroids in SZ patients, even though the
      presence of altered neurosteroid pathways in the circulating blood and/or brain
      remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic
      benefits have also been linked to the regulation of neurosteroid signaling.
      Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone
      affect a broad spectrum of behavioral functions through their unique molecular
      characteristics and may represent innovative therapeutic targets for SZ. Future
      investigations in larger cohorts with long-term follow-ups will be required to
      ascertain the neuropsychopharmacological role of this yet unexploited class of
      neurosteroid agents.

PMID- 29568277
TI  - The Development and Validation of the Bergen-Yale Sex Addiction Scale With a
      Large National Sample.
AB  - The view that problematic excessive sexual behavior ("sex addiction") is a form
      of behavioral addiction has gained more credence in recent years, but there is
      still considerable controversy regarding operationalization of the concept.
      Furthermore, most previous studies have relied on small clinical samples. The
      present study presents a new method for assessing sex addiction-the Bergen-Yale
      Sex Addiction Scale (BYSAS)-based on established addiction components (i.e.,
      salience/craving, mood modification, tolerance, withdrawal, conflict/problems,
      and relapse/loss of control). Using a cross-sectional survey, the BYSAS was
      administered to a broad national sample of 23,533 Norwegian adults [aged 16-88
      years; mean (+/- SD) age = 35.8 +/- 13.3 years], together with validated measures
      of the Big Five personality traits, narcissism, self-esteem, and a measure of
      sexual addictive behavior. Both an exploratory and a confirmatory factor analysis
      (RMSEA = 0.046, CFI = 0.998, TLI = 0.996) supported a one-factor solution,
      although a local dependence between two items (Items 1 and 2) was detected.
      Furthermore, the scale had good internal consistency (Cronbach's alpha = 0.83).
      The BYSAS correlated significantly with the reference scale (r = 0.52), and
      demonstrated similar patterns of convergent and discriminant validity. The BYSAS
      was positively related to extroversion, neuroticism, intellect/imagination, and
      narcissism, and negatively related to conscientiousness, agreeableness, and self
      esteem. High scores on the BYSAS were more prevalent among those who were men,
      single, of younger age, and with higher education. The BYSAS is a brief, and
      psychometrically reliable and valid measure for assessing sex addiction. However,
      further validation of the BYSAS is needed in other countries and contexts.

PMID- 29568278
TI  - Depression, Hopelessness, and Complicated Grief in Survivors of Suicide.
AB  - Suicide often has a severe impact on the surviving family and friends. There is a
      need to better understand the psychological and psychopathological consequences
      of losing a significant other by suicide. The aim of the present study was to
      assess hopelessness, depression, suicide risk, complicated grief, intrusive
      memories, and avoidance in a sample of suicide survivors. In this observational
      study, 35 bereaved individuals were recruited at the Suicide Prevention Centre of
      Sant'Andrea Hospital in Rome. Individuals were administered a series of validated
      instruments: the Beck Depression Inventory II (BDI), the Beck Hopelessness Scale
      (BHS), the Inventory of Complicated Grief (ICG), the Impact of Event Scale (IES),
      the Subjective Happiness Scale (SHS), and the Satisfaction With Life Scale
      (SWLS). Most survivors (62.8%) obtained high scores on measures of complicated
      grief. Scores on the measure of complicated grief were associated with
      intrusiveness of thoughts and memories, attempts to prevent the thoughts and
      emotions related to the event, depressive symptoms and hopelessness, and lower
      scores for feelings of happiness and satisfaction with life. A subgroup of
      suicide survivors may be at risk of severe psychological distress and suicidal
      behavior. Identification of these survivors is a necessary step for providing
      appropriate counseling and psychotherapy.

PMID- 29568279
TI  - Aging and the Change in Fatigue and Sleep - A Longitudinal Study Across 8 Years
      in Three Age Groups.
AB  - Fatigue is prevalent in the population and usually linked to sleep problems, and
      both are related to age. However, previous studies have been cross-sectional. The
      purpose of the present study was to investigate the trajectories of sleep and
      fatigue across 8 years of aging in a large group (N > 8.000) of individuals. A
      second purpose was to investigate whether fatigue trajectories would differ
      between age groups, and whether different trajectories of fatigue would be
      reflected in a corresponding difference in trajectories for sleep variables.
      Results from mixed model analyses showed that fatigue decreased across 8 years in
      all age groups, while sleep problems increased, non-restorative sleep decreased,
      weekend sleep duration decreased, and weekday sleep duration showed different
      patterns depending on age. Furthermore, the larger the decrease in fatigue, the
      larger was the increase in sleep duration across years, the lower was the
      increase of sleep problems, and the larger was the decrease of non-restorative
      sleep. The results suggest that aging has positive effects on fatigue and sleep
      and that these changes are linked.

PMID- 29568280
TI  - Preliminary Checklist for Reporting Observational Studies in Sports Areas:
      Content Validity.
AB  - Observational studies are based on systematic observation, understood as an
      organized recording and quantification of behavior in its natural context.
      Applied to the specific area of sports, observational studies present advantages
      when comparing studies based on other designs, such as the flexibility for
      adapting to different contexts and the possibility of using non-standardized
      instruments as well as a high degree of development in specific software and data
      analysis. Although the importance and usefulness of sports-related observational
      studies have been widely shown, there is no checklist to report these studies.
      Consequently, authors do not have a guide to follow in order to include all of
      the important elements in an observational study in sports areas, and reviewers
      do not have a reference tool for assessing this type of work. To resolve these
      issues, this article aims to develop a checklist to measure the quality of sports
      related observational studies based on a content validity study. The participants
      were 22 judges with at least 3 years of experience in observational studies,
      sports areas, and methodology. They evaluated a list of 60 items systematically
      selected and classified into 12 dimensions. They were asked to score four aspects
      of each item on 5-point Likert scales to measure the following dimensions:
      representativeness, relevance, utility, and feasibility. The judges also had an
      open-format section for comments. The Osterlind index was calculated for each
      item and for each of the four aspects. Items were considered appropriate when
      obtaining a score of at least 0.5 in the four assessed aspects. After considering
      these inclusion criteria and all of the open-format comments, the resultant
      checklist consisted of 54 items grouped into the same initial 12 dimensions.
      Finally, we highlight the strengths of this work. We also present its main
      limitation: the need to apply the resultant checklist to obtain data and, thus,
      increase quality indicators of its psychometric properties. For this reason, as
      relevant actions for further development, we encourage expert readers to use it
      and provide feedback; we plan to apply it to different sport areas.

PMID- 29568281
TI  - Quantitative Analysis of Bradykinesia and Rigidity in Parkinson's Disease.
AB  - Background: In the last decades, several studies showed that wearable sensors,
      used for assessing Parkinson's disease (PD) motor symptoms and recording their
      fluctuations, could provide a quantitative and reliable tool for patient's motor
      performance monitoring. Objective: The aim of this study is to make a step
      forward the capability of quantitatively describing PD motor symptoms. The
      specific aims are: identify the most sensible place where to locate sensors to
      monitor PD bradykinesia and rigidity, and identify objective indexes able to
      discriminate PD OFF/ON motor status, and PD patients from healthy subjects (HSs).
      Methods: Fourteen PD patients (H&Y stage 1-2.5), and 13 age-matched HSs, were
      enrolled. Five magneto-inertial wearable sensors, placed on index finger, thumb,
      metacarpus, wrist, and arm, were used as motion tracking systems. Sensors were
      placed on the most affected arm of PD patients, and on dominant hand of HS. Three
      UPDRS part III tasks were evaluated: rigidity (task 22), finger tapping (task
      23), and prono-supination movements of the hands (task 25). A movement disorders
      expert rated the three tasks according to the UPDRS part III scoring system. In
      order to describe each task, different kinematic indexes from sensors were
      extracted and analyzed. Results: Four kinematic indexes were extracted:
      fatigability; total time; total power; smoothness. The last three well-described
      PD OFF/ON motor status, during finger-tapping task, with an index finger sensor.
      During prono-supination task, wrist sensor was able to differentiate PD OFF/ON
      motor condition. Smoothness index, used as a rigidity descriptor, provided a good
      discrimination of the PD OFF/ON motor status. Total power index, showed the best
      accuracy for PD vs healthy discrimination, with any sensor location among index
      finger, thumb, metacarpus, and wrist. Conclusion: The present study shows that,
      in order to better describe the kinematic features of Parkinsonian movements,
      wearable sensors should be placed on a distal location on upper limb, on index
      finger or wrist. The proposed indexes demonstrated a good correlation with
      clinical scores, thus providing a quantitative tool for research purposes in
      future studies in this field.

PMID- 29568282
TI  - Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord
      Derived Mesenchymal Stem Cells in Neonatal Stroke Mice.
AB  - Neonatal brain injury induced by stroke causes significant disability, including
      cerebral palsy, and there is no effective therapy for stroke. Recently,
      mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell
      based therapies. In this study, we examined the safety and efficacy of
      intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in
      neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion
      at postnatal day 12 (P12), and low-dose (1 * 104) or high-dose (1 * 105) UC-MSCs
      were administered intravenously 48 h after the insult (P14). To evaluate the
      effect of the UC-MSC treatment, neurological behavior and cerebral blood flow
      were measured, and neuroanatomical analysis was performed at P28. To investigate
      the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in
      vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were
      performed. Functional disability was significantly improved in the high-dose UC
      MSC group when compared with the vehicle group, but cerebral blood flow and
      cerebral hemispheric volume were not restored by UC-MSC therapy. The level of
      exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h
      after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were
      trapped in the lungs and disappeared in a week without migration toward the brain
      or other organs. We found that systemic blood flow was stable over the 10 min
      after cell administration and that there were no differences in mortality among
      the groups. Immunohistopathological assessment showed that the percent area of
      Iba1-positive staining in the peri-infarct cortex was significantly reduced with
      the high-dose UC-MSC treatment compared with the vehicle treatment. These results
      suggest that intravenous administration of UC-MSCs is safe for a mouse model of
      neonatal stroke and improves dysfunction after middle cerebral artery occlusion
      by modulating the microglial reaction in the peri-infarct cortex.

PMID- 29568283
TI  - Comparative Genomics of the Baltic Sea Toxic Cyanobacteria Nodularia spumigena
      UHCC 0039 and Its Response to Varying Salinity.
AB  - Salinity is an important abiotic factor controlling the distribution and
      abundance of Nodularia spumigena, the dominating diazotrophic and toxic
      phototroph, in the brackish water cyanobacterial blooms of the Baltic Sea. To
      expand the available genomic information for brackish water cyanobacteria, we
      sequenced the isolate Nodularia spumigena UHCC 0039 using an Illumina-SMRT hybrid
      sequencing approach, revealing a chromosome of 5,294,286 base pairs (bp) and a
      single plasmid of 92,326 bp. Comparative genomics in Nostocales showed pronounced
      genetic similarity among Nodularia spumigena strains evidencing their short
      evolutionary history. The studied Baltic Sea strains share similar sets of CRISPR
      Cas cassettes and a higher number of insertion sequence (IS) elements compared to
      Nodularia spumigena CENA596 isolated from a shrimp production pond in Brazil.
      Nodularia spumigena UHCC 0039 proliferated similarly at three tested salinities,
      whereas the lack of salt inhibited its growth and triggered transcriptome
      remodeling, including the up-regulation of five sigma factors and the down
      regulation of two other sigma factors, one of which is specific for strain UHCC
      0039. Down-regulated genes additionally included a large genetic region for the
      synthesis of two yet unidentified natural products. Our results indicate a
      remarkable plasticity of the Nodularia salinity acclimation, and thus salinity
      strongly impacts the intensity and distribution of cyanobacterial blooms in the
      Baltic Sea.

PMID- 29568284
TI  - Geobacter Dominates the Inner Layers of a Stratified Biofilm on a Fluidized Anode
      During Brewery Wastewater Treatment.
AB  - In this study, we designed a microbial electrochemical fluidized bed reactor (ME
      FBR), with an electroconductive anodic bed made of activated carbon particles for
      treating a brewery wastewater. Under a batch operating mode, acetate and
      propionate consumption rates were 13-fold and 2.4-fold higher, respectively, when
      the fluidized anode was polarized (0.2 V) with respect to open circuit
      conditions. Operating in a continuous mode, this system could effectively treat
      the brewery effluent at organic loading rates (OLR) over 1.7 kg m-3NRV d-1 and
      with removal efficiencies of 95 +/- 1.4% (hydraulic retention time of 1 day and
      an influent of 1.7 g-COD L-1). The coulombic efficiency values highly depended
      upon the OLR applied, and varied from a 56 +/- 15% to 10 +/- 1%. Fluorescence in
      situ hybridization (FISH) analysis revealed a relative high abundance of
      Geobacter species (ca. 20%), and clearly showed a natural microbial
      stratification. Interestingly, the Geobacter cluster was highly enriched in the
      innermost layers of the biofilm (thickness of 10 MUm), which were in contact with
      the electroconductive particles of bed, whereas the rest of bacteria were located
      in the outermost layers. To our knowledge, this is the first time that such a
      clear microbial stratification has been observed on an anode-respiring biofilm.
      Our results revealed the relevant role of Geobacter in switching between the
      electrode and other microbial communities performing metabolic reactions in the
      outermost environment of the biofilm.

PMID- 29568285
TI  - Leishmania donovani Activates Hypoxia Inducible Factor-1alpha and miR-210 for
      Survival in Macrophages by Downregulation of NF-kappaB Mediated Pro-inflammatory
      Immune Response.
AB  - Micro RNAs (miRNAs) have emerged as a critical regulator of several biological
      processes in both animals and plants. They have also been associated with
      regulation of immune responses in many human diseases during recent years.
      Visceral leishmaniasis (VL) is the most severe form of leishmaniasis, which is
      characterized by impairment of both innate and adaptive immune responses. In the
      present study, we observed that Leishmania establishes hypoxic environment in
      host macrophages that induces the expression of hypoxia inducible factor-1alpha
      (HIF-1alpha) and miRNA-210. Further, the expression of miRNA-210 was found to be
      dependent on activation of HIF-1alpha expression. The HIF-1alpha silencing by
      siRNA resulted in significantly (p < 0.001) decreased expression of miR-210 in
      parasites infected macrophages. We also observed that in siHIF-1alpha or
      antagomir-210 treated L. donovani infected macrophages, the parasitic load and
      percentage infectivity were significantly (p < 0.001) decreased. Furthermore, we
      found that inhibition of miR-210 leads to activation of NF-kappaB subunit p50,
      and it forms heterodimer with p65 and translocates into the nucleus from the
      cytoplasm. This significantly (p < 0.05) induced the transcription of pro
      inflammatory cytokines genes such as TNF-alpha and IL-12 in miRNA-210 inhibited
      macrophages compared to uninhibited macrophages whereas the level of IL-10, an
      anti-inflammatory cytokine, was found to be significantly decreased (p < 0.001).
      These findings suggested that L. donovani infection induces hypoxic environment
      inside the macrophages that activates HIF-1alpha. Further, HIF-1alpha upregulates
      miR-210, which eventually establishes a suitable environment for the survival of
      parasite inside the host macrophages by downregulating NF-kappaB mediated pro
      inflammatory immune responses.

PMID- 29568287
TI  - The Human Polyomavirus Middle and Alternative T-Antigens; Thoughts on Roles and
      Relevance to Cancer.
AB  - Approximately 15-20% of human cancer is related to infection, which renders them
      potentially preventable by antimicrobial or antiviral therapy. Human
      polyomaviruses (PyVs) are relevant in this regard, as illustrated by the
      involvement of Merkel cell polyomavirus (MCPyV) in the development of Merkel cell
      carcinoma. The polyomavirus Small and Large tumor antigen (ST and LT) have been
      extensively studied with respect to their role in oncogenesis. Recently it was
      shown that a number of human PyVs, including MCPyV and the trichodysplasia
      spinulosa polyomavirus (TSPyV), express additional T-antigens called Middle T
      (MT) and alternative T (ALT). ALT is encoded by ORF5, also known as the
      alternative T open reading frame (ALTO), which also encodes the second exon of
      MT, and overlaps out-of-frame with the second exon of LT. Previously, MT was
      considered unique for oncogenic rodent polyomaviruses, and ALT was still unknown.
      In this mini-review, we want to point out there are important reasons to explore
      the involvement of MT and ALT in human cellular transformation. First, just like
      their rodent equivalents, MT and ALT probably disrupt cellular pathways that
      control signaling and proliferation. Second, expression of the MT and ALT
      encoding ORF5/ALTO characterizes a monophyletic polyomavirus clade that includes
      human and animal PyVs with known oncogenic potential. And third, ORF5/ALTO is
      subject to strong positive selection aimed specifically at a short linear motif
      within MT and ALT that overlaps completely with the RB-binding motif in LT. The
      latter suggests tight interplay between these T-antigens with possible
      consequences for cell transformation.

PMID- 29568286
TI  - Inhibition of TGF-beta and NOTCH Signaling by Cutaneous Papillomaviruses.
AB  - Infections with cutaneous papillomaviruses have been linked to cutaneous squamous
      cell carcinomas that arise in patients who suffer from a rare genetic disorder,
      epidermodysplasia verruciformis, or those who have experienced long-term,
      systemic immunosuppression following organ transplantation. The E6 proteins of
      the prototypical cutaneous human papillomavirus (HPV) 5 and HPV8 inhibit TGF-beta
      and NOTCH signaling. The Mus musculus papillomavirus 1, MmuPV1, infects
      laboratory mouse strains and causes cutaneous skin warts that can progress to
      squamous cell carcinomas. MmuPV1 E6 shares biological and biochemical activities
      with HPV8 E6 including the ability to inhibit TGF-beta and NOTCH signaling by
      binding the SMAD2/SMAD3 and MAML1 transcription factors, respectively. Inhibition
      of TGF-beta and NOTCH signaling is linked to delayed differentiation and
      sustained proliferation of differentiating keratinocytes. Furthermore, the
      ability of MmuPV1 E6 to bind MAML1 is necessary for wart and cancer formation in
      experimentally infected mice. Hence, experimental MmuPV1 infection in mice will
      be a robust and valuable experimental system to dissect key aspects of cutaneous
      HPV infection, pathogenesis, and carcinogenesis.

PMID- 29568288
TI  - Serological Evidence of Orthopoxvirus Circulation Among Equids, Southeast Brazil.
AB  - Since 1999 Vaccinia virus (VACV) outbreaks involving bovines and humans have been
      reported in Brazil; this zoonosis is known as Bovine Vaccinia (BV) and is mainly
      an occupational disease of milkers. It was only in 2008 (and then again in 2011
      and 2014) however, that VACV was found causing natural infections in Brazilian
      equids. These reports involved only equids, no infected humans or bovines were
      identified, and the sources of infections remain unknown up to date. The
      peculiarities of Equine Vaccinia outbreaks (e.g., absence of human infection),
      the frequently shared environments, and fomites by equids and bovines in
      Brazilian farms and the remaining gaps in BV epidemiology incited a question over
      OPV serological status of equids in Brazil. For this report, sera from 621 equids
      - representing different species, ages, sexes and locations of origin within
      Minas Gerais State, southeast Brazil - were examined for the presence of anti
      Orthopoxvirus (OPV) antibodies. Only 74 of these were sampled during an Equine
      Vaccinia outbreak, meaning some of these specific animals presented typical
      lesions of OPV infections. The majority of sera, however, were sampled from
      animals without typical signs of OPV infection and during the absence of reported
      Bovine or Equine Vaccinia outbreaks. Results suggest the circulation of VACV
      among equids of southeast Brazil even prior to the time of the first VACV
      outbreak in 2008. There is a correlation of OPVs outbreaks among bovines and
      equids although many gaps remain to our understanding of its nature. The data
      obtained may even be carefully associated to recent discussion over OPVs history.
      Moreover, data is available to improve the knowledge and instigate new researches
      regarding OPVs circulation in Brazil and worldwide.

PMID- 29568289
TI  - An Ontology Systems Approach on Human Brain Expression and Metaproteomics.
AB  - Research in the last decade has shown growing evidence of the gut microbiota
      influence on brain physiology. While many mechanisms of this influence have been
      proposed in animal models, most studies in humans are the result of a pathology
      dysbiosis association and very few have related the presence of certain taxa with
      brain substructures or molecular pathways. In this paper, we associated the
      functional ontologies in the differential expression of brain substructures from
      the Allen Brain Atlas database, with those of the metaproteome from the Human
      Microbiome Project. Our results showed several coherent clustered ontologies
      where many taxa could influence brain expression and physiology. A detailed
      analysis of psychobiotics showed specific slim ontologies functionally associated
      with substructures in the basal ganglia and cerebellar cortex. Some of the most
      relevant slim ontology groups are related to Ion transport, Membrane potential,
      Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant
      neuropathology found was Parkinson disease. In some of these cases, new
      hypothetical gut microbiota-brain interaction pathways are proposed.

PMID- 29568290
TI  - Anti-adhesion Property of the Potential Probiotic Strain Lactobacillus fermentum
      8711 Against Methicillin-Resistant Staphylococcus aureus (MRSA).
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant
      pathogen and one of the leading causes of nosocomial infection worldwide.
      Probiotic bacteria play a significant role in preventive or therapeutic
      interventions of gastrointestinal infections in human as well as animals. In this
      study, we have investigated the adhesion property of the probiotic strain
      Lactobacillus fermentum MTCC 8711 and its ability to prevent the adhesion of MRSA
      to human colon adenocarcinoma cells, Caco-2. We have shown that L. fermentum
      could efficiently adhere to the Caco-2 cells. Also, we have shown that L.
      fermentum significantly reduced MRSA adhesion to Caco-2 cells. Three types of
      experiments were performed to assess the anti-adhesion property of L. fermentum
      against MRSA. Inhibition (Caco-2 cells were pre-treated with L. fermentum, and
      subsequently MRSA was added), competition (both L. fermentum and MRSA were added
      to Caco-2 cells simultaneously), and displacement or exclusion (Caco-2 cells were
      pre-treated with MRSA, and subsequently L. fermentum was added). In all three
      experiments, adhesion of MRSA was significantly reduced. Interestingly, L.
      fermentum could efficiently displace the adhered MRSA, and hence this probiotic
      can be used for therapeutic applications also. In cytotoxicity assay, we found
      that L. fermentum per se was not cytotoxic, and also significantly reduced the
      MRSA-induced cytotoxicity. The protective effect occurred without affecting Caco
      2 cell morphology and viability.

PMID- 29568291
TI  - Macroalgae Extracts From Antarctica Have Antimicrobial and Anticancer Potential.
AB  - Background: Macroalgae are sources of bioactive compounds due to the large number
      of secondary metabolites they synthesize. The Antarctica region is characterized
      by extreme weather conditions and abundant aggregations of macroalgae. However,
      current knowledge on their biodiversity and their potential for bio-prospecting
      is still fledging. This study evaluates the antimicrobial and cytotoxic activity
      of different extracts of four macroalgae (Cystosphaera jacquinotii, Iridaea
      cordata, Himantothallus grandifolius, and Pyropia endiviifolia) from the
      Antarctic region against cancer and non-cancer cell lines. Methods: The
      antimicrobial activity of macroalgae was evaluated by the broth microdilution
      method. Extracts were assessed against Staphylococcus aureus ATCC 19095,
      Enterococcus faecalis ATCC 4083, Escherichia coli ATCC29214, Pseudomonas
      aeruginosa ATCC 9027, Candida albicans ATCC 62342, and the clinical isolates from
      the human oral cavity, namely, C. albicans (3), C. parapsilosis, C. glabrata, C.
      lipolytica, and C. famata. Cytotoxicity against human epidermoid carcinoma (A
      431) and mouse embryonic fibroblast (NIH/3T3) cell lines was evaluated with MTT
      colorimetric assay. Results: An ethyl acetate extract of H. grandifolius showed
      noticeable antifungal activity against all fungal strains tested, including
      fluconazole-resistant samples. Cytotoxicity investigation with a cancer cell line
      revealed that the ethyl acetate extract of I. cordata was highly cytotoxic
      against A-431 cancer cell line, increasing the inhibitory ratio to 91.1 and 95.6%
      after 24 and 48 h exposure, respectively, for a concentration of 500 MUg mL-1.
      Most of the algal extracts tested showed little or no cytotoxicity against
      fibroblasts. Conclusion: Data suggest that macroalgae extracts from Antarctica
      may represent a source of therapeutic agents. HIGHLIGHTS Different macroalgae
      samples from Antarctica were collected and the lyophilized biomass of each
      macroalgae was extracted sequentially with different solventsThe antimicrobial
      and anticancer potential of macroalgae extracts were evaluatedEthyl acetate
      extract of H. grandifolius showed noticeable antifungal activity against all the
      fungal strains tested, including fluconazole-resistant samplesEthyl acetate
      extract of I. cordata was highly cytotoxic against the A-431 cancer cell lineMost
      of the algal extracts tested showed little or no cytotoxicity against normal cell
      lines.

PMID- 29568292
TI  - Arbuscular Mycorrhizal Fungi Negatively Affect Nitrogen Acquisition and Grain
      Yield of Maize in a N Deficient Soil.
AB  - Arbuscular mycorrhizal fungi (AMF) play a crucial role in enhancing the
      acquisition of immobile nutrients, particularly phosphorus. However, because
      nitrogen (N) is more mobile in the soil solution and easier to access by plants
      roots, the role of AMF in enhancing N acquisition is regarded as less important
      for host plants. Because AMF have a substantial N demand, competition for N
      between AMF and plants particularly under low N condition is possible. Thus, it
      is necessary to know whether or not AMF affect N uptake of plants and thereby
      affect plant growth under field conditions. We conducted a 2-year field trial and
      pot experiments in a greenhouse by using benomyl to suppress colonization of
      maize roots by indigenous AMF at both low and high N application rates. Benomyl
      reduced mycorrhizal colonization of maize plants in all experiments. Benomyl
      treated maize had a higher shoot N concentration and content and produced more
      grain under field conditions. Greenhouse pot experiments showed that benomyl also
      enhanced maize growth and N concentration and N content when the soil was not
      sterilized, but had no effect on maize biomass and N content when the soil was
      sterilized but a microbial wash added, providing evidence that increased plant
      performance is at least partly caused by direct effects of benomyl on AMF. We
      conclude that AMF can reduce N acquisition and thereby reduce grain yield of
      maize in N-limiting soils.

PMID- 29568293
TI  - Incomplete Selective Sweeps of Microcystis Population Detected by the Leader-End
      CRISPR Fragment Analysis in a Natural Pond.
AB  - The freshwater cyanobacterium Microcystis aeruginosa frequently forms toxic
      massive blooms and exists in an arms race with its infectious phages in aquatic
      natural environments, and as a result, has evolved extremely diverse and
      elaborate antiviral defense systems, including the clustered regularly
      interspaced short palindromic repeats (CRISPR)-CRISPR-associated genes (Cas)
      system. Here, to assess Microcystis population dynamics associated with exogenous
      mobile genetic elements such as phages and plasmids, we examined the temporal
      variation in CRISPR genotypes (CTs) by analyzing spacer sequences detected in a
      natural pond between June and October 2013 when a cyanobacterial bloom occurred.
      A total of 463,954 high-quality leader-end CRISPR sequences were obtained and the
      sequences containing spacers were classified into 31 previously reported CTs and
      68 new CTs based on the shared order of the leader-end spacers. CT19 was the most
      dominant genotype (32%) among the 16 most common CTs, followed by CT52 (14%) and
      CT58 (9%). Spacer repertoires of CT19 showed mainly two different types;
      CT19origin, which was identical to the CT19 spacer repertoire of previously
      isolated strains, and CT19new+, which contained a new spacer at the leader-end of
      the CRISPR region of CT19origin, which were present in almost equal abundance,
      accounting for up to 99.94% of CT19 sequences. Surprisingly, we observed the
      spacer repertoires of the second to tenth spacers of CT19origin at the most
      leader-end of proto-genotype sequences of CT19origin. These were observed during
      the sampling in this study and our previous study at the same ecosystem in 2010
      and 2011, suggesting these CTs persisted from 2011 to 2013 in spite of phage
      pressure. The leader-end variants were observed in other CT genotypes. These
      findings indicated an incomplete selective sweep of Microcystis populations. We
      explained the phenomenon as follow; the abundance of Microcystis varied
      seasonally and drastically, resulting that Microcystis populations experience a
      bottleneck once a year, and thereby founder effects following a bottleneck mean
      that older CTs have an equal chance of increasing in prevalence as the CTs
      generated following acquisition of newer spacers.

PMID- 29568294
TI  - PlMAPK10, a Mitogen-Activated Protein Kinase (MAPK) in Peronophythora litchii, Is
      Required for Mycelial Growth, Sporulation, Laccase Activity, and Plant Infection.
AB  - Mitogen-activated protein kinase (MAPK) pathways are ubiquitous and
      evolutionarily conserved signal transduction modules directing cellular respond
      to a diverse array of stimuli, in the eukaryotic organisms. In this study,
      PlMAPK10 was identified to encode a MAPK in Peronophythora litchii, the oomycete
      pathogen causing litchi downy blight disease. PlMAPK10, containing a specific and
      highly conserved dual phosphorylation lip sequence SEY (Serine-Glutamic
      Tyrosine), represents a novel group of MAPKs as previously reported.
      Transcriptional profiling showed that PlMAPK10 expression was up-regulated in
      zoospore and cyst stages. To elucidate its function, the PlMAPK10 gene was
      silenced by stable transformation. PlMAPK10 silence did not impair oospore
      production, sporangium germination, zoospore encyst, or cyst germination but
      hindered hyphal growth, sporulation, pathogenicity, likely due to altering
      laccase activity. Over all, our results indicated that a MAPK encoded by PlMAPK10
      gene in P. litchii is important for pathogenic development.

PMID- 29568295
TI  - Drosophila GATA Factor Serpent Establishes Phagocytic Ability of Embryonic
      Macrophages.
AB  - During Drosophila embryogenesis, a large number of apoptotic cells are
      efficiently engulfed and degraded by professional phagocytes, macrophages.
      Phagocytic receptors Six-Microns-Under (SIMU), Draper (Drpr) and Croquemort (Crq)
      are specifically expressed in embryonic macrophages and required for their
      phagocytic function. However, how this function is established during development
      remains unclear. Here we demonstrate that the key regulator of Drosophila
      embryonic hemocyte differentiation, the transcription factor Serpent (Srp), plays
      a central role in establishing macrophage phagocytic competence. Srp, a homolog
      of the mammalian GATA factors, is required and sufficient for the specific
      expression of SIMU, Drpr and Crq receptors in embryonic macrophages. Moreover, we
      show that each of these receptors can significantly rescue phagocytosis defects
      of macrophages in srp mutants, including their distribution in the embryo and
      engulfment of apoptotic cells. This reveals that the proficiency of macrophages
      to remove apoptotic cells relies on the expression of SIMU, Crq and/or Drpr.
      However, Glial Cells Missing (GCM) acting downstream of Srp in the
      differentiation of hemocytes, is dispensable for their phagocytic function during
      embryogenesis. Taken together, our study discloses the molecular mechanism
      underlying the development of macrophages as skilled phagocytes of apoptotic
      cells.

PMID- 29568296
TI  - Many Routes to an Antibody Heavy-Chain CDR3: Necessary, Yet Insufficient, for
      Specific Binding.
AB  - Because of its great potential for diversity, the immunoglobulin heavy-chain
      complementarity-determining region 3 (HCDR3) is taken as an antibody molecule's
      most important component in conferring binding activity and specificity. For this
      reason, HCDR3s have been used as unique identifiers to investigate adaptive
      immune responses in vivo and to characterize in vitro selection outputs where
      display systems were employed. Here, we show that many different HCDR3s can be
      identified within a target-specific antibody population after in vitro selection.
      For each identified HCDR3, a number of different antibodies bearing differences
      elsewhere can be found. In such selected populations, all antibodies with the
      same HCDR3 recognize the target, albeit at different affinities. In contrast,
      within unselected populations, the majority of antibodies with the same HCDR3
      sequence do not bind the target. In one HCDR3 examined in depth, all target
      specific antibodies were derived from the same VDJ rearrangement, while non
      binding antibodies with the same HCDR3 were derived from many different V and D
      gene rearrangements. Careful examination of previously published in vivo datasets
      reveals that HCDR3s shared between, and within, different individuals can also
      originate from rearrangements of different V and D genes, with up to 26 different
      rearrangements yielding the same identical HCDR3 sequence. On the basis of these
      observations, we conclude that the same HCDR3 can be generated by many different
      rearrangements, but that specific target binding is an outcome of unique
      rearrangements and VL pairing: the HCDR3 is necessary, albeit insufficient, for
      specific antibody binding.

PMID- 29568297
TI  - NKG2D: A Master Regulator of Immune Cell Responsiveness.
AB  - NKG2D is an activating receptor that is mostly expressed on cells of the
      cytotoxic arm of the immune system. Ligands of NKG2D are normally of low
      abundance, but can be induced in virtually any cell in response to stressors,
      such as infection and oncogenic transformation. Engagement of NKG2D stimulates
      the production of cytokines and cytotoxic molecules and traditionally this
      receptor is, therefore, viewed as a molecule that mediates direct responses
      against cellular threats. However, accumulating evidence indicates that this
      classical view is too narrow. During NK cell development, engagement of NKG2D has
      a long-term impact on the expression of NK cell receptors and their
      responsiveness to extracellular cues, suggesting a role in NK cell education.
      Upon chronic NKG2D engagement, both NK and T cells show reduced responsiveness of
      a number of activating receptors, demonstrating a role of NKG2D in induction of
      peripheral tolerance. The image that emerges is that NKG2D can mediate both
      inhibitory and activating signals, which depends on the intensity and duration of
      ligand engagement. In this review, we provide an overview of the impact of NKG2D
      stimulation during hematopoietic development and during acute and chronic
      stimulation in the periphery on responsiveness of other receptors than NKG2D. We
      propose that NKG2D interprets the context of the immunological environment
      through detection of cellular cues and in response sets the appropriate
      activation threshold for a large number of immune receptors. This perspective is
      of particular importance for future therapies that aim to exploit NKG2D signaling
      to fight tumors or infection.

PMID- 29568298
TI  - Trying to See the Forest through the Trees: Deciphering the Nature of Memory
      Immunity to Mycobacterium tuberculosis.
AB  - The purpose of vaccination against tuberculosis and other diseases is to
      establish a heightened state of acquired specific resistance in which the memory
      immune response is capable of mediating an accelerated and magnified expression
      of protection to the pathogen when this is encountered at a later time. In the
      earliest studies in mice infected with Mycobacterium tuberculosis, memory
      immunity and the cells that express this were definable both in terms of kinetics
      of emergence, and soon thereafter by the levels of expression of markers
      including CD44, CD62L, and the chemokine receptor CCR7, allowing the
      identification of effector memory and central memory T cell subsets. Despite
      these initial advances in knowledge, more recent information has not revealed
      more clarity, but instead, has created a morass of complications-complications
      that, if not resolved, could harm correct vaccine design. Here, we discuss two
      central issues. The first is that we have always assumed that memory is induced
      in the same way, and consists of the same T cells, regardless of whether that
      immunity is generated by BCG vaccination, or by exposure to M. tuberculosis
      followed by effective chemotherapy. This assumption is almost certainly
      incorrect. Second, a myriad of additional memory subsets have now been described,
      such as resident, stem cell-like, tissue specific, among others, but as yet we
      know nothing about the relative importance of each, or whether if a new vaccine
      needs to induce all of these, or just some, to be fully effective.

PMID- 29568299
TI  - New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical
      Impacts and Regulatory Mechanisms.
AB  - Currently, tumor-infiltrating B lymphocytes have been recognized as a new
      hallmark of breast cancer (BC). The function seems to be controversial, either
      with positive, negative, or no significance in BC's prediction and prognosis.
      Moreover, B-cell infiltrates regulate tumor process through productions of
      antibodies and interleukin-10. The interactions with other lymphocytes and
      programmed death-1/PD-1 ligand axis are also documented. The regulatory
      mechanisms will eventually be incorporated into diagnostic and therapeutic
      algorithms, thus give guide to clinical treatment. In this review, we give new
      insights into clinical impacts and regulatory mechanisms of tumor-infiltrating B
      cells, which heralds a new era in immuno-oncology in BC treatment.

PMID- 29568300
TI  - Tailoring Immune Responses toward Autoimmunity: Transcriptional Regulators That
      Drive the Creation and Collusion of Autoreactive Lymphocytes.
AB  - T-dependent humoral immune responses to infection involve a collaboration between
      B and CD4 T cell activation, migration, and co-stimulation, thereby culminating
      in the formation of germinal centers (GCs) and eventual differentiation into
      memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive
      the formation of a tailored B cell response. Downstream of these signals are
      transcriptional regulators that are the critical enactors of immune cell
      programs. In particular, a core group of transcription factors regulate both B
      and T cell differentiation, identity, and function. The timing and expression
      levels of these transcription factors are tightly controlled, with dysregulated
      expression correlated to immune cell dysfunction in autoimmunity and
      lymphomagenesis. Recent studies have significantly advanced our understanding of
      both extrinsic and intrinsic regulators of autoreactive B cells and antibody
      secreting PCs in systemic lupus erythematosus, rheumatoid arthritis, and other
      autoimmune conditions. Yet, there are still gaps in our understanding of the
      causative role these regulators play, as well as the link between lymphoid
      responses and peripheral damage. This review will focus on the genesis of
      immunopathogenic CD4 helper and GC B cells. In particular, we will detail the
      transcriptional regulation of cytokine and chemokine receptor signaling during
      the pathogenesis of GC-derived autoimmune conditions in both murine models and
      human patients.

PMID- 29568301
TI  - Arabidopsis PCaP2 Plays an Important Role in Chilling Tolerance and ABA Response
      by Activating CBF- and SnRK2-Mediated Transcriptional Regulatory Network.
AB  - Chilling stress affects plant growth and productivity. However, the multi
      underlying mechanisms of chilling tolerance are not well understood. Arabidopsis
      PCaP2 is involved in regulating the dynamic of microtubules (MTs) and F-actin and
      Ca2+-binding ability. Here, the results showed that the PCaP2 expression was
      highly induced in roots, cotyledons, true leaves, lateral roots and flowers under
      cold stress. Compared with the wild type, PCaP2-overexpressing plants displayed
      the enhanced tolerance, whereas its RNAi and mutant were more sensitive in seed
      germination, seedling and reproductive growth under chilling stress in
      Arabidopsis. In addition, PCaP2 was also a positive regulator of ABA signaling
      pathway by analyzing the expression of PCaP2 and the phenotypes of PCaP2
      overexpressing, mutant and RNAi plants under ABA treatment. Interestingly,
      disruption of PCaP2 inhibited the expression of CBF1, -3 and CBF-target COR
      genes, while increased the CBF2 expression in response to cold or ABA. Moreover,
      we found that SnRK2s were involved in cold stress and PCaP2 mutants down
      regulated the transcription level of SnRK2.2, -2.3 and SnRK2-mediated downstream
      genes including ABF2, RD29A, KIN1, KIN2, but up-regulated SnRK2.6, ABF1, -3, -4
      in ABA and cold treatments. It is well-accepted that PCaP2 as a Ca2+-binding
      protein triggers the gene expression to enhance plant chilling tolerance. Our
      further studies showed that MT destabilizing activity of PCaP2, but not F-actin
      severing function, may be involved in chilling stress. Taken together, our
      results highlight that PCaP2 plays an important role in chilling tolerance and
      ABA response by triggering the CBF- and SnRK2-meditated transcriptional
      regulatory pathways, providing novel evidences of underlying mechanisms of multi
      pathways in chilling stress.

PMID- 29568303
TI  - European Forest Cover During the Past 12,000 Years: A Palynological
      Reconstruction Based on Modern Analogs and Remote Sensing.
AB  - Characterization of land cover change in the past is fundamental to understand
      the evolution and present state of the Earth system, the amount of carbon and
      nutrient stocks in terrestrial ecosystems, and the role played by land-atmosphere
      interactions in influencing climate. The estimation of land cover changes using
      palynology is a mature field, as thousands of sites in Europe have been
      investigated over the last century. Nonetheless, a quantitative land cover
      reconstruction at a continental scale has been largely missing. Here, we present
      a series of maps detailing the evolution of European forest cover during last
      12,000 years. Our reconstructions are based on the Modern Analog Technique (MAT):
      a calibration dataset is built by coupling modern pollen samples with the
      corresponding satellite-based forest-cover data. Fossil reconstructions are then
      performed by assigning to every fossil sample the average forest cover of its
      closest modern analogs. The occurrence of fossil pollen assemblages with no
      counterparts in modern vegetation represents a known limit of analog-based
      methods. To lessen the influence of no-analog situations, pollen taxa were
      converted into plant functional types prior to running the MAT algorithm. We then
      interpolate site-specific reconstructions for each timeslice using a four
      dimensional gridding procedure to create continuous gridded maps at a continental
      scale. The performance of the MAT is compared against methodologically
      independent forest-cover reconstructions produced using the REVEALS method. MAT
      and REVEALS estimates are most of the time in good agreement at a trend level,
      yet MAT regularly underestimates the occurrence of densely forested situations,
      requiring the application of a bias correction procedure. The calibrated MAT
      based maps draw a coherent picture of the establishment of forests in Europe in
      the Early Holocene with the greatest forest-cover fractions reconstructed between
      ~8,500 and 6,000 calibrated years BP. This forest maximum is followed by a
      general decline in all parts of the continent, likely as a result of
      anthropogenic deforestation. The continuous spatial and temporal nature of our
      reconstruction, its continental coverage, and gridded format make it suitable for
      climate, hydrological, and biogeochemical modeling, among other uses.

PMID- 29568302
TI  - A Canonical DREB2-Type Transcription Factor in Lily Is Post-translationally
      Regulated and Mediates Heat Stress Response.
AB  - Based on studies of monocot crops and eudicot model plants, the DREB2 class of
      AP2-type transcription factor has been shown to play crucial roles in various
      abiotic stresses, especially in the upstream of the heat stress response;
      however, research on DREB2s has not been reported in non-gramineous monocot
      plants. Here, we identified a novel DREB2 (LlDREB2B) from lily (Lilium
      longiflorum), which was homologous to AtDREB2A of Arabidopsis, OsDREB2B of rice,
      and ZmDREB2A of maize. LlDREB2B was induced by heat, cold, salt, and mannitol
      stress, and its protein had transcriptional activity, was located in the nucleus,
      was able to bind to the dehydration-responsive element (DRE), and participated in
      the heat-responsive pathway of HsfA3. Overexpression of LlDREB2B in Arabidopsis
      activated expression of downstream genes and improved thermotolerance. LlDREB2B
      was not regulated by alternative splicing; functional transcripts accumulated
      under either normal or heat-stress conditions. A potential PEST sequence was
      predicted in LlDREB2B, but the stability of the LlDREB2B protein was not
      positively affected when the predicated PEST sequence was deleted. Further
      analysis revealed that the predicated PEST sequence lacked a SBC or SBC-like
      motif allowing interaction with BPMs and required for negative regulation.
      Nevertheless, LlDREB2B was still regulated at the post-translational level by
      interaction with AtDRIP1 and AtDRIP2 of Arabidopsis. In addition, LlDREB2B also
      interacted with AtRCD1 and LlRCD1 via a potential RIM motif located at amino
      acids 215-245. Taken together, our results show that LlDREB2B participated in the
      establishment of thermotolerance, and its regulation was different from that of
      the orthologs of gramineous and eudicot plants.

PMID- 29568305
TI  - Mapping the Flowering of an Invasive Plant Using Unmanned Aerial Vehicles: Is
      There Potential for Biocontrol Monitoring?
AB  - Invasion by alien species is a worldwide phenomenon with negative consequences at
      both natural and production areas. Acacia longifolia is an invasive shrub/small
      tree well known for its negative ecological impacts in several places around the
      world. The recent introduction of a biocontrol agent (Trichilogaster
      acaciaelongifoliae), an Australian bud-galling wasp which decreases flowering of
      A. longifolia, in Portugal, demands the development of a cost-efficient method to
      monitor its establishment. We tested how unmanned aerial vehicles (UAV) can be
      used to map A. longifolia flowering. Our core assumption is as the population of
      the biocontrol agent increases, its impacts on the reduction of A. longifolia
      flowering will be increasingly visible. Additionally, we tested if there is a
      simple linear correlation between the number of flowers of A. longifolia counted
      in field and the area covered by flowers in the UAV imagery. UAV imagery was
      acquired over seven coastal areas including frontal dunes, interior sand dunes
      and pine forests considering two phenological stages: peak and off-peak flowering
      season. The number of flowers of A. longifolia was counted, in a minimum of 60 1
      m2 quadrats per study area. For each study area, flower presence/absence maps
      were obtained using supervised Random Forest. The correlation between the number
      of flowers and the area covered by flowering plants could then be tested. The
      flowering of A. longifolia was mapped using UAV mounted with RGB and CIR Cannon
      IXUS/ELPH cameras (Overall Accuracy > 0.96; Cohen's Kappa > 0.85) varying
      according to habitat type and flowering season. The correlation between the
      number of flowers counted and the area covered by flowering was weak (r2 between
      0.0134 and 0.156). This is probably explained, at least partially, by the high
      variability of A. longifolia in what regards flowering morphology and
      distribution. The very high accuracy of our approach to map A. longifolia
      flowering proved to be cost efficient and replicable, showing great potential for
      detecting the future decrease in flowering promoted by the biocontrol agent. The
      attempt to provide a low-cost method to estimate A. longifolia flower
      productivity using UAV failed, but it provided valuable insights on the future
      steps.

PMID- 29568304
TI  - Early Cold-Induced Peroxidases and Aquaporins Are Associated With High Cold
      Tolerance in Dajiao (Musa spp. 'Dajiao').
AB  - Banana is an important tropical fruit with high economic value. One of the main
      cultivars ('Cavendish') is susceptible to low temperatures, while another closely
      related specie ('Dajiao') has considerably higher cold tolerance. We previously
      reported that some membrane proteins appear to be involved in the cold tolerance
      of Dajiao bananas via an antioxidation mechanism. To investigate the early cold
      stress response of Dajiao, here we applied comparative membrane proteomics
      analysis for both cold-sensitive Cavendish and cold-tolerant Dajiao bananas
      subjected to cold stress at 10 degrees C for 0, 3, and 6 h. A total of 2,333 and
      1,834 proteins were identified in Cavendish and Dajiao, respectively. Subsequent
      bioinformatics analyses showed that 692 Cavendish proteins and 524 Dajiao
      proteins were predicted to be membrane proteins, of which 82 and 137
      differentially abundant membrane proteins (DAMPs) were found in Cavendish and
      Dajiao, respectively. Interestingly, the number of DAMPs with increased abundance
      following 3 h of cold treatment in Dajiao (80) was seven times more than that in
      Cavendish (11). Gene ontology molecular function analysis of DAMPs for Cavendish
      and Dajiao indicated that they belong to eight categories including hydrolase
      activity, binding, transporter activity, antioxidant activity, etc., but the
      number in Dajiao is twice that in Cavendish. Strikingly, we found peroxidases
      (PODs) and aquaporins among the protein groups whose abundance was significantly
      increased after 3 h of cold treatment in Dajiao. Some of the PODs and aquaporins
      were verified by reverse-transcription PCR, multiple reaction monitoring, and
      green fluorescent protein-based subcellular localization analysis, demonstrating
      that the global membrane proteomics data are reliable. By combining the
      physiological and biochemical data, we found that membrane-bound Peroxidase 52
      and Peroxidase P7, and aquaporins (MaPIP1;1, MaPIP1;2, MaPIP2;4, MaPIP2;6,
      MaTIP1;3) are mainly involved in decreased lipid peroxidation and maintaining
      leaf cell water potential, which appear to be the key cellular adaptations
      contributing to the cold tolerance of Dajiao. This membrane proteomics study
      provides new insights into cold stress tolerance mechanisms of banana, toward
      potential applications for ultimate genetic improvement of cold tolerance in
      banana.

PMID- 29568306
TI  - Can Leaf Water Content Be Estimated Using Multispectral Terrestrial Laser
      Scanning? A Case Study With Norway Spruce Seedlings.
AB  - Changing climate is increasing the amount and intensity of forest stress agents,
      such as drought, pest insects, and pathogens. Leaf water content, measured here
      in terms of equivalent water thickness (EWT), is an early indicator of tree
      stress that provides timely information about the health status of forests.
      Multispectral terrestrial laser scanning (MS-TLS) measures target geometry and
      reflectance simultaneously, providing spatially explicit reflectance information
      at several wavelengths. EWT and leaf internal structure affect leaf reflectance
      in the shortwave infrared region that can be used to predict EWT with MS-TLS. A
      second wavelength that is sensitive to leaf internal structure but not affected
      by EWT can be used to normalize leaf internal effects on the shortwave infrared
      region and improve the prediction of EWT. Here we investigated the relationship
      between EWT and laser intensity features using multisensor MS-TLS at 690, 905,
      and 1,550 nm wavelengths with both drought-treated and Endoconidiophora polonica
      inoculated Norway spruce seedlings to better understand how MS-TLS measurements
      can explain variation in EWT. In our study, a normalized ratio of two wavelengths
      at 905 and 1,550 nm and length of seedling explained 91% of the variation (R2) in
      EWT as the respective prediction accuracy for EWT was 0.003 g/cm2 in greenhouse
      conditions. The relation between EWT and the normalized ratio of 905 and 1,550 nm
      wavelengths did not seem sensitive to a decreased point density of the MS-TLS
      data. Based on our results, different EWTs in Norway spruce seedlings show
      different spectral responses when measured using MS-TLS. These results can be
      further used when developing EWT monitoring for improving forest health
      assessments.

PMID- 29568307
TI  - Two Splicing Variants of OsNPF7.7 Regulate Shoot Branching and Nitrogen
      Utilization Efficiency in Rice.
AB  - Rice includes 93 nitrate and peptide transporters family (NPF) members that
      facilitate the soil uptake and internal reallocation of nitrogen for growth and
      development. This study demonstrated that OsNPF7.7 had two splicing variants, and
      altered expression of each variant could regulate shoot branching and nitrogen
      utilization efficiency (NUtE) in rice. The expression of both variants was down
      regulated in the buds by increased nitrogen level in the Japonica rice variety
      ZH11. The expression level of long-variant OsNPF7.7-1 was higher in panicles at
      reproductive stage, however, the expression level of short-variant OsNPF7.7-2 was
      higher in buds and leaves at vegetative stage compared to each other in ZH11.
      OsNPF7.7-1 was localized in the plasma membrane, whereas OsNPF7.7-2 was localized
      in the vacuole membrane. Furthermore, the results indicated that the expression
      level of each variant for OsNPF7.7 determined axillary bud outgrowth, and then
      influenced the rice tiller number. Overexpression of OsNPF7.7-1 could promote
      nitrate influx and concentration in root, whereas overexpression of OsNPF7.7-2
      could improve ammonium influx and concentration in root. RNAi and osnpf7.7 lines
      of OsNPF7.7 showed an increased amount of amino acids in leaf sheaths, but a
      decreased amount in leaf blades, which affected nitrogen allocation and plant
      growth. The elevated expression of each variant for OsNPF7.7 in ZH11 enhanced
      NUtE using certain fertilization regimes under paddy field conditions. Moreover,
      overexpression of each variant for OsNPF7.7 in KY131 increased significantly the
      filled grain number per plant. Thus, increased each variant of OsNPF7.7 has the
      potential to improve grain yield and NUtE in rice.

PMID- 29568308
TI  - Plant Glycine-Rich Proteins in Stress Response: An Emerging, Still Prospective
      Story.
AB  - Seed plants are sessile organisms that have developed a plethora of strategies
      for sensing, avoiding, and responding to stress. Several proteins, including the
      glycine-rich protein (GRP) superfamily, are involved in cellular stress responses
      and signaling. GRPs are characterized by high glycine content and the presence of
      conserved segments including glycine-containing structural motifs composed of
      repetitive amino acid residues. The general structure of this superfamily
      facilitates division of GRPs into five main subclasses. Although the
      participation of GRPs in plant stress response has been indicated in numerous
      model and non-model plant species, relatively little is known about the key
      physiological processes and molecular mechanisms in which those proteins are
      engaged. Class I, II, and IV members are known to be involved in hormone
      signaling, stress acclimation, and floral development, and are crucial for
      regulation of plant cells growth. GRPs of class IV [RNA-binding proteins (RBPs)]
      are involved in alternative splicing or regulation of transcription and stomatal
      movement, seed, pollen, and stamen development; their accumulation is regulated
      by the circadian clock. Owing to the fact that the overexpression of GRPs can
      confer tolerance to stress (e.g., some are involved in cold acclimation and may
      improve growth at low temperatures), these proteins could play a promising role
      in agriculture through plant genetic engineering. Consequently, isolation,
      cloning, characterization, and functional validation of novel GRPs expressed in
      response to the diverse stress conditions are expected to be growing areas of
      research in the coming years. According to our knowledge, this is the first
      comprehensive review on participation of plant GRPs in the response to diverse
      stress stimuli.

PMID- 29568309
TI  - Recurrent Transformation of Prior Knowledge Based Model for Human Motion
      Recognition.
AB  - Motion related human activity recognition using wearable sensors can potentially
      enable various useful daily applications. So far, most studies view it as a stand
      alone mathematical classification problem without considering the physical nature
      and temporal information of human motions. Consequently, they suffer from data
      dependencies and encounter the curse of dimension and the overfitting issue.
      Their models are hard to be intuitively understood. Given a specific motion set,
      if structured domain knowledge could be manually obtained, it could be used for
      better recognizing certain motions. In this study, we start from a deep analysis
      on natural physical properties and temporal recurrent transformation
      possibilities of human motions and then propose a useful Recurrent Transformation
      Prior Knowledge-based Decision Tree (RT-PKDT) model for recognition of specific
      human motions. RT-PKDT utilizes temporal information and hierarchical
      classification method, making the most of sensor streaming data and human
      knowledge to compensate the possible data inadequacy. The experiment results
      indicate that the proposed method performs superior to those adopted in related
      works, such as SVM, BP neural networks, and Bayesian Network, obtaining an
      accuracy of 96.68%.

PMID- 29568310
TI  - n-Iterative Exponential Forgetting Factor for EEG Signals Parameter Estimation.
AB  - Electroencephalograms (EEG) signals are of interest because of their relationship
      with physiological activities, allowing a description of motion, speaking, or
      thinking. Important research has been developed to take advantage of EEG using
      classification or predictor algorithms based on parameters that help to describe
      the signal behavior. Thus, great importance should be taken to feature extraction
      which is complicated for the Parameter Estimation (PE)-System Identification (SI)
      process. When based on an average approximation, nonstationary characteristics
      are presented. For PE the comparison of three forms of iterative-recursive uses
      of the Exponential Forgetting Factor (EFF) combined with a linear function to
      identify a synthetic stochastic signal is presented. The one with best results
      seen through the functional error is applied to approximate an EEG signal for a
      simple classification example, showing the effectiveness of our proposal.

PMID- 29568311
TI  - Enhanced Ant Colony Optimization with Dynamic Mutation and Ad Hoc Initialization
      for Improving the Design of TSK-Type Fuzzy System.
AB  - This paper proposes an enhanced ant colony optimization with dynamic mutation and
      ad hoc initialization, ACODM-I, for improving the accuracy of Takagi-Sugeno-Kang-
      (TSK-) type fuzzy systems design. Instead of the generic initialization usually
      used in most population-based algorithms, ACODM-I proposes an ad hoc application
      specific initialization for generating the initial ant solutions to improve the
      accuracy of fuzzy system design. The generated initial ant solutions are
      iteratively improved by a new approach incorporating the dynamic mutation into
      the existing continuous ACO (ACOR). The introduced dynamic mutation balances the
      exploration ability and convergence rate by providing more diverse search
      directions in the early stage of optimization process. Application examples of
      two zero-order TSK-type fuzzy systems for dynamic plant tracking control and one
      first-order TSK-type fuzzy system for the prediction of the chaotic time series
      have been simulated to validate the proposed algorithm. Performance comparisons
      with ACOR and different advanced algorithms or neural-fuzzy models verify the
      superiority of the proposed algorithm. The effects on the design accuracy and
      convergence rate yielded by the proposed initialization and introduced dynamic
      mutation have also been discussed and verified in the simulations.

PMID- 29568312
TI  - Prevalence and Associated Symptoms of Helicobacter pylori Infection among
      Schoolchildren in Kassala State, East of Sudan.
AB  - This study aimed to determine the prevalence of H. pylori infections among
      schoolchildren and investigate the associations between H. pylori seropositivity
      and existence of gastrointestinal symptoms. Methods. A prospective cross
      sectional study was conducted during a period from January to December 2012 at
      Kassala state, east of Sudan. Schoolchildren from different primary schools were
      enrolled in the study. Sociodemographic characteristics and gastrointestinal
      symptoms were recorded from each child. A rapid immunochromatographic test was
      performed for the detection of H. pylori IgG antibodies. Data on patient
      demographic characteristics, clinical diagnosis, and findings of H. pylori
      infection were analyzed by simple descriptive statistics. Results. Among 431
      schoolchildren, H. pylori seropositivity was found to be 21.8%. The majority of
      children (79; 84%) had BMI below the normal range. The most frequent symptoms
      associated with H. pylori infections were nausea (25.5%), followed by gastric
      pain (24.5%) and heart pain (20.2%). There were statistically significant
      differences in H. pylori seropositivity between boys and girls (p = 0.003).
      Conclusions. The prevalence of H. pylori infection among schoolchildren in
      Kassala city has been documented. Although the majority of the disease was
      associated with several gastrointestinal symptoms, the role of infection in the
      etiology of abdominal symptoms needs further investigations.

PMID- 29568313
TI  - The in vitro effects of a novel estradiol analog on cell proliferation and
      morphology in human epithelial cervical carcinoma.
AB  - Background: The majority of novel chemotherapeutics target the cell cycle, aiming
      to effect arrest and cause apoptosis. One such agent, 2-methoxyestradiol (2ME),
      has been shown to possess anticancer properties against numerous cancer types,
      both in vitro and in vivo. Despite its promise, 2ME has exhibited limitations,
      including low oral bioavailability and rapid hepatic enzymatic inactivation in
      vivo. A novel sulphamoylated estrogen analog, 2-ethyl-3-O-sulphamoyl-estra
      1,3,5(10)16-tetraene (ESE-16), was in silico-designed in our laboratory to
      overcome these issues. It was then synthesized by a pharmaceutical company and
      used in an in vitro antiproliferative effect study on a human cervical carcinoma
      (HeLa) cell line. Results: Cell proliferation data obtained from the crystal
      violet assay and real-time cell analysis demonstrated that 0.2 MUM of ESE-16 had
      a significant inhibitory effect on the HeLa cells 24 h post-exposure.
      Immunofluorescence showed that ESE-16 is a microtubule disruptor that causes
      cells to undergo a mitotic block. Qualitative morphological studies using
      polarization-optical transmitted light differential interference contrast
      (PlasDIC) and light microscopy revealed a decrease in cell density and an
      increase in the number of cells arrested in metaphase. After ESE-16 exposure,
      hallmarks of apoptosis were also observed, including membrane blebbing, chromatin
      condensation and the presence of apoptotic bodies. Flow cytometry provided
      quantitative results from cell cycle progression analysis, indicating cells
      undergoing apoptosis and cells in the G2/M phase of the cell cycle, confirming
      cell cycle arrest in metaphase after ESE-16 treatment. Quantification of the ESE
      16-mediated upregulation of cyclin B in HeLa cells and spectrophotometric and
      flow cytometric confirmation of cell death via apoptosis further confirmed the
      substance's impact. Conclusion: ESE-16 exerts its antiproliferative effects
      through microtubule disruption, which induces a mitotic block culminating in
      apoptosis. This research provided information on ESE-16 as a potential antitumor
      agent and on cellular targets that could aid in the design of prospective
      microtubule-disrupting compounds. Further in vitro and in vivo investigations of
      this novel compound are needed.

PMID- 29568314
TI  - Platelet lysate induces chondrogenic differentiation of umbilical cord-derived
      mesenchymal stem cells.
AB  - Purpose: Articular cartilage has a poor capacity for self-repair, and thus still
      presents a major challenge in orthopedics. Mesenchymal stem cells (MSCs) are
      multipotent stem cells with the potential to differentiate into chondrocytes in
      the presence of transforming growth factor beta (TGF-beta). Platelet lysate (PL)
      contains a relatively large number of growth factors, including TGF-beta, and has
      been shown to ameliorate cartilage repair. Here, we investigated the ability of
      PL to direct chondrogenic differentiation of MSCs along with other standard
      differentiation components in a pellet culture system. Methods: We isolated and
      expanded MSCs from human umbilical cords using a PL-supplemented medium and
      characterized the cells based on immunophenotype and potential for
      differentiation to adipocytes and osteocytes. We further cultured MSCs as pellets
      in a chondrogenic-differentiation medium supplemented with PL. After 21 days, the
      pellets were processed for histological analysis and stained with alician blue
      and acridine orange. The expression of SOX9 was investigated using RT-PCR.
      Results: MSCs maintained their stemness characteristics in the PL-supplemented
      medium. However, the distribution of cells in the pellets cultured in the PL
      supplemented chondrogenic differentiation medium had a greater similarity to
      cartilage tissue-derived chondrocytes than to the negative control. The intense
      alician blue staining indicated an increased production of mucopolysaccharides in
      the differentiated pellets, which also showed elevated expression of SOX9.
      Conclusions: Our data suggest that MSCs could be differentiated to chondrocytes
      in the presence of PL and absence of exogenous TGF-beta. Further research needs
      to be conducted to understand the exact role and potential of PL in chondrogenic
      differentiation and chondrocyte regeneration.

PMID- 29568315
TI  - Feeding ecology in sea spiders (Arthropoda: Pycnogonida): what do we know?
AB  - Sea spiders (Pycnogonida) are a widespread and phylogenetically important group
      of marine arthropods. However, their biology remains understudied, and detailed
      information about their feeding ecology is difficult to find. Observations on
      pycnogonid feeding are scattered in the literature, often in older sources
      written in various languages, and have never been comprehensively summarized.
      Here we provide an overview of all information on feeding in pycnogonids that we
      have been able to find and review what is known on feeding specializations and
      preferences in the various pycnogonid taxa. We deduce general findings where
      possible and outline future steps necessary to gain a better understanding of the
      feeding ecology of one of the world's most bizarre animal taxa.

PMID- 29568316
TI  - Chemical and behavioral integration of army ant-associated rove beetles - a
      comparison between specialists and generalists.
AB  - Host-symbiont interactions are embedded in ecological communities and range from
      unspecific to highly specific relationships. Army ants and their arthropod guests
      represent a fascinating example of species-rich host-symbiont associations where
      host specificity ranges across the entire generalist - specialist continuum. In
      the present study, we compared the behavioral and chemical integration mechanisms
      of two extremes of the generalist - specialist continuum: generalist ant
      predators in the genus Tetradonia (Staphylinidae: Aleocharinae: Athetini), and
      specialist ant-mimics in the genera Ecitomorpha and Ecitophya (Staphylinidae:
      Aleocharinae: Ecitocharini). Similar to a previous study of Tetradonia beetles,
      we combined DNA barcoding with morphological studies to define species boundaries
      in ant-mimicking beetles. This approach found four ant-mimicking species at our
      study site at La Selva Biological Station in Costa Rica. Community sampling of
      Eciton army ant parasites revealed that ant-mimicking beetles were perfect host
      specialists, each beetle species being associated with a single Eciton species.
      These specialists were seamlessly integrated into the host colony, while
      generalists avoided physical contact to host ants in behavioral assays. Analysis
      of the ants' nestmate recognition cues, i.e. cuticular hydrocarbons (CHCs),
      showed close similarity in CHC composition and CHC concentration between
      specialists and Eciton burchellii foreli host ants. On the contrary, the chemical
      profiles of generalists matched host profiles less well, indicating that high
      accuracy in chemical host resemblance is only accomplished by socially integrated
      species. Considering the interplay between behavior, morphology, and cuticular
      chemistry, specialists but not generalists have cracked the ants' social code
      with respect to various sensory modalities. Our results support the long-standing
      idea that the evolution of host-specialization in parasites is a trade-off
      between the range of potential host species and the level of specialization on
      any particular host.

PMID- 29568317
TI  - Rapeseed oil fortified with micronutrients can reduce glucose intolerance during
      a high fat challenge in rats.
AB  - Background: Better choices of dietary lipid sources and substitution of refined
      by fortified oils could reduce the intake of saturated fatty acids (FA) and
      increase the intake of omega 3 FA concomitantly to healthy bioactive compounds.
      Methods: The development of obesity and metabolic disturbances was explored in
      rats fed during 11 weeks with a high fat diet (HFD) in which the amount of
      saturated and polyunsaturated FA was respectively reduced and increased, using
      rapeseed oil as lipid source. This oil was used in a refined form (R) or
      fortified (10 fold increase in concentration) with endogenous micronutrients
      (coenzyme Q10 + tocopherol only (RF) only and also with canolol (RFC)). The
      effect of substituting palm by rapeseed oil was analysed using a student t test,
      oil fortification was analysed using ANOVA statistical test. Results: Despite a
      similar weight gain, diets R, RF and RFC improved glucose tolerance (+ 10%) of
      the rats compared to a standard HFD with palm and sunflower oils as lipid source.
      Plasma glucose was lowered in RF and RFC groups (- 15 and 23% respectively),
      although triacylglycerol level was only reduced in group RFC (- 33%) compared to
      R. The fortification with canolol promoted the activation of Akt and AMP
      activated protein kinase (AMPK) in skeletal muscle and subcutaneous adipose
      tissue respectively. Canolol supplementation also led to reduce p38 MAPK
      activation in skeletal muscle. Conclusions: This study suggests that the presence
      of endogenous micronutrients in rapeseed oil promotes cellular adaptations to
      reverse glucose intolerance and improve the metabolism of insulin sensitive
      tissues.

PMID- 29568318
TI  - An innovative light chamber for measuring photosynthesis by three-dimensional
      plant organs.
AB  - Background: In plants, three-dimensional (3-D) organs such as inflorescences or
      fruits carry out photosynthesis and thus play a significant role in carbon
      assimilation and yield. However, this contribution has been poorly characterized
      because there is no reliable method for measuring photosynthesis by 3-D organs.
      One of the major challenges is ensuring the uniform irradiation of samples that
      are placed within a sealed chamber. Results: In this study, we developed an
      innovative chamber with homogeneous lighting that can be used to measure
      photosynthesis by large 3-D organs. It consisted of a 15-cm-long sealed
      transparent cylinder that was surrounded by a decagonal prismatic light source,
      made up of a mixture of red and blue LEDs. We characterized irradiance
      homogeneity within the chamber at a resolution level of 1 cm and 10 degrees .
      Photosynthetic photon flux density (PPFD) along the central axis of the chamber
      could be set to any value between 100 and 1100 umol m-2 s-1. The coefficient of
      variation for the irradiation values found throughout the chamber was 10% and
      that for the ratio of red-to-blue spectra was less than 1.5%. The temperature of
      the sample was regulated to stay within 1  degrees C of the target temperature,
      regardless of PPFD. We compared the performance of our device with that of a
      commercially available device employing unidirectional lighting. Specifically, we
      examined net photosynthesis in two sample types-wheat ears and grape clusters-at
      varying PPFD levels. Conclusions: The devices gave similar estimates of dark
      respiration, regardless of sample type or age. Conversely, net photosynthesis
      started to become asymptotic at lower irradiance levels in our device than in the
      conventional device because apparent quantum yield was three times higher. When
      examining the effects of irradiance heterogeneity, it was clear that biased
      estimates could result from systems employing unidirectional light sources. Our
      results also confirmed that our chamber could be a useful tool for obtaining more
      accurate estimates of photosynthesis by 3-D organs.

PMID- 29568319
TI  - Wheat ear counting in-field conditions: high throughput and low-cost approach
      using RGB images.
AB  - Background: The number of ears per unit ground area (ear density) is one of the
      main agronomic yield components in determining grain yield in wheat. A fast
      evaluation of this attribute may contribute to monitoring the efficiency of crop
      management practices, to an early prediction of grain yield or as a phenotyping
      trait in breeding programs. Currently the number of ears is counted manually,
      which is time consuming. Moreover, there is no single standardized protocol for
      counting the ears. An automatic ear-counting algorithm is proposed to estimate
      ear density under field conditions based on zenithal color digital images taken
      from above the crop in natural light conditions. Field trials were carried out at
      two sites in Spain during the 2014/2015 crop season on a set of 24 varieties of
      durum wheat with two growing conditions per site. The algorithm for counting uses
      three steps: (1) a Laplacian frequency filter chosen to remove low and high
      frequency elements appearing in an image, (2) a Median filter to reduce high
      noise still present around the ears and (3) segmentation using Find Maxima to
      segment local peaks and determine the ear count within the image. Results: The
      results demonstrate high success rate (higher than 90%) between the algorithm
      counts and the manual (image-based) ear counts, and precision, with a low
      standard deviation (around 5%). The relationships between algorithm ear counts
      and grain yield was also significant and greater than the correlation with manual
      (field-based) ear counts. In this approach, results demonstrate that automatic
      ear counting performed on data captured around anthesis correlated better with
      grain yield than with images captured at later stages when the low performance of
      ear counting at late grain filling stages was associated with the loss of
      contrast between canopy and ears. Conclusions: Developing robust, low-cost and
      efficient field methods to assess wheat ear density, as a major agronomic
      component of yield, is highly relevant for phenotyping efforts towards increases
      in grain yield. Although the phenological stage of measurements is important, the
      robust image analysis algorithm presented here appears to be amenable from aerial
      or other automated platforms.

PMID- 29568321
TI  - Evaluation of Treatment Effect with Paired Failure Times in a Single-Arm Phase II
      Trial in Oncology.
AB  - In early phase clinical trials of cytotoxic drugs in oncology, the efficacy is
      typically evaluated based on the tumor shrinkage. However, this criterion is not
      always appropriate for more recent cytostatic agents, and alternative endpoints
      have been proposed. The growth modulation index (GMI), defined as the ratio
      between the times to progression in two successive treatment lines, has been
      proposed for a single-arm phase II trials. The treatment effect is evaluated by
      estimating the rate of patients having a GMI superior to a given threshold. To
      estimate this rate, we investigated a parametric method based on the distribution
      of the times to progression and a nonparametric one based on a midrank estimator.
      Through simulations, we studied their operating characteristics and the impact of
      different design parameters (censoring, dependence, and distribution) on them. In
      these simulations, the nonparametric estimator slightly underestimated the rate
      and had slightly overconservative confidence intervals in some cases. Conversely,
      the parametric estimator overestimated the rate and had anticonservative
      confidence intervals in some cases. The nonparametric method appeared to be more
      robust to censoring than the parametric one. In conclusion, we recommend the
      nonparametric method, but the parametric method can be used as a supplementary
      tool.

PMID- 29568320
TI  - Protein arginine methylation: an emerging regulator of the cell cycle.
AB  - Protein arginine methylation is a common post-translational modification where a
      methyl group is added onto arginine residues of a protein to alter detection by
      its binding partners or regulate its activity. It is known to be involved in many
      biological processes, such as regulation of signal transduction, transcription,
      facilitation of protein-protein interactions, RNA splicing and transport. The
      enzymes responsible for arginine methylation, protein arginine methyltransferases
      (PRMTs), have been shown to methylate or associate with important regulatory
      proteins of the cell cycle and DNA damage repair pathways, such as cyclin D1,
      p53, p21 and the retinoblastoma protein. Overexpression of PRMTs resulting in
      aberrant methylation patterns in cancers often correlates with poor recovery
      prognosis. This indicates that protein arginine methylation is also an important
      regulator of the cell cycle, and consequently a target for cancer regulation. The
      effect of protein arginine methylation on the cell cycle and how this emerging
      key player of cell cycle regulation may be used in therapeutic strategies for
      cancer are the focus of this review.

PMID- 29568322
TI  - Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor
      Dysfunctions.
AB  - After menopause, decreased levels of estrogen and progesterone remodel the
      collagen of the soft tissues thereby reducing their stiffness. Stress urinary
      incontinence is associated with involuntary urine leakage due to pathological
      movement of the pelvic organs resulting from lax suspension system, fasciae, and
      ligaments. This study compares the changes in the orientation and position of the
      female pelvic organs due to weakened fasciae, ligaments, and their combined
      laxity. A mixture theory weighted by respective volume fraction of elastin
      collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is
      adopted to characterize the mechanical behaviour of the fascia. The load carrying
      response (other than the functional response to the pelvic organs) of each fascia
      component, pelvic organs, muscles, and ligaments are assumed to be isotropic,
      hyperelastic, and incompressible. Finite element simulations are conducted during
      Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A
      significant dislocation of the urethrovesical junction is observed due to
      weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The
      dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is
      associated with urethral-bladder hypermobility, greater levator plate angulation,
      and positive Q-tip test which are observed in incontinent females.

PMID- 29568323
TI  - OCTAL: Optimal Completion of gene trees in polynomial time.
AB  - Background: For a combination of reasons (including data generation protocols,
      approaches to taxon and gene sampling, and gene birth and loss), estimated gene
      trees are often incomplete, meaning that they do not contain all of the species
      of interest. As incomplete gene trees can impact downstream analyses, accurate
      completion of gene trees is desirable. Results: We introduce the Optimal Tree
      Completion problem, a general optimization problem that involves completing an
      unrooted binary tree (i.e., adding missing leaves) so as to minimize its distance
      from a reference tree on a superset of the leaves. We present OCTAL, an algorithm
      that finds an optimal solution to this problem when the distance between trees is
      defined using the Robinson-Foulds (RF) distance, and we prove that OCTAL runs in
      [Formula: see text] time, where n is the total number of species. We report on a
      simulation study in which gene trees can differ from the species tree due to
      incomplete lineage sorting, and estimated gene trees are completed using OCTAL
      with a reference tree based on a species tree estimated from the multi-locus
      dataset. OCTAL produces completed gene trees that are closer to the true gene
      trees than an existing heuristic approach in ASTRAL-II, but the accuracy of a
      completed gene tree computed by OCTAL depends on how topologically similar the
      reference tree (typically an estimated species tree) is to the true gene tree.
      Conclusions: OCTAL is a useful technique for adding missing taxa to incomplete
      gene trees and provides good accuracy under a wide range of model conditions.
      However, results show that OCTAL's accuracy can be reduced when incomplete
      lineage sorting is high, as the reference tree can be far from the true gene
      tree. Hence, this study suggests that OCTAL would benefit from using other types
      of reference trees instead of species trees when there are large topological
      distances between true gene trees and species trees.

PMID- 29568324
TI  - The role of bacteria in cancer therapy - enemies in the past, but allies at
      present.
AB  - In recent decades, bacteria's therapeutic role has aroused attention in medicinal
      and pharmaceutical research. While bacteria are considered among the primary
      agents for causing cancer, recent research has shown intriguing results
      suggesting that bacteria can be effective agents for cancer treatment - they are
      the perfect vessels for targeted cancer therapy. Several bacterial
      strains/species have been discovered to possess inherent oncolytic potentials to
      invade and colonize solid tumors in vivo. The therapeutic strategy of using
      bacteria for treating cancer is considered to be effective; however, the severe
      side effects encountered during the treatment resulted in the abandonment of the
      therapy. State-of-the-art genetic engineering has been recently applied to
      bacteria therapy and resulted in a greater efficacy with minimum side effects. In
      addition, the anti-cancer potential of tumor-targeting bacteria through oral
      administration circumvents the use of the intravenous route and the associated
      adverse effects. This review aims to provide a comprehensive summary of the
      latest literature on the role of bacteria in cancer treatment.

PMID- 29568325
TI  - Correction to: Purging behaviors relate to impaired subjective sleep quality in
      female patients with anorexia nervosa: a prospective observational study.
AB  - [This corrects the article DOI: 10.1186/s13030-017-0107-7.].

PMID- 29568326
TI  - Determinants of early child development in rural Tanzania.
AB  - Background: It has been estimated that more than 200 million children under the
      age of five do not reach their full potential in cognitive development. Much of
      what we know about brain development is based on research from high-income
      countries. There is limited evidence on the determinants of early child
      development in low-income countries, especially rural sub-Saharan Africa. The
      present study aimed to identify the determinants of cognitive development in
      children living in villages surrounding Haydom, a rural area in north-central
      Tanzania. Methods: This cohort study is part of the MAL-ED (The Interactions of
      Malnutrition & Enteric Infections: Consequences for Child Health and Development)
      multi-country consortium studying risk factors for ill health and poor
      development in children. Descriptive analysis and linear regression analyses were
      performed. Associations between nutritional status, socio-economic status, and
      home environment at 6 months of age and cognitive outcomes at 15 months of age
      were studied. The third edition of the Bayley Scales for Infant and Toddler
      Development was used to assess cognitive, language and motor development.
      Results: There were 262 children enrolled into the study, and this present
      analysis included the 137 children with data for 15-month Bayley scores.
      Univariate regression analysis, weight-for-age and weight-for-length z-scores at
      6 months were significantly associated with 15-month Bayley gross motor score,
      but not with other 15-month Bayley scores. Length-for-age z-scores at 6 months
      were not significantly associated with 15-month Bayley scores. The socio-economic
      status, measured by a set of assets and monthly income was significantly
      associated with 15-month Bayley cognitive score, but not with language, motor,
      nor total 15-month Bayley scores. Other socio-economic variables were not
      significantly associated with 15-month Bayley scores. No significant associations
      were found between the home environment and 15-month Bayley scores. In
      multivariate regression analyses we found higher Bayley scores for girls and
      higher Bayley scores in families with more assets. Adjusted R-squared of this
      model was 8%. Conclusion: We conclude that poverty is associated with a slower
      cognitive development in children and malnutrition is associated with slower
      gross motor development. This information should encourage authorities and other
      stakeholders to invest in improved welfare and nutrition programmes for children
      from early infancy.

PMID- 29568328
TI  - Nusinersen for spinal muscular atrophy.

PMID- 29568327
TI  - Synthetic pathways and processes for effective production of 5-hydroxytryptophan
      and serotonin from glucose in Escherichia coli.
AB  - Background: Tryptophan derivatives such as 5-hydroxytryptophan (5HTP) and
      serotonin are valuable molecules with pharmaceutical interest. 5HTP is presently
      mainly obtained by extraction from the plant Griffonia simplicifolia and
      serotonin is produced by chemical synthesis. A simple biotechnological method for
      the production of these compounds is desired. Results: In a first attempt to
      synthesize serotonin from glucose, we used a single engineered Escherichia coli
      strain and observed a low production of maximal 0.8 +/- 0.2 mg/L of serotonin,
      probably due to the undesired site-reaction of direct decarboxylation of
      tryptophan and the consequent decrease of the precursor 5HTP. To circumvent this
      problem, we have constructed a stepwise system in which the 5HTP production and
      the serotonin conversion are separated. 962 +/- 58 mg/L of 5HTP was produced in
      the first step using a recombinant strain with a semi-rationally engineered
      aromatic amino acid hydroxylase, the highest concentration reported so far. In a
      subsequent step of 5HTP bioconversion using a recombinant strain harboring a
      tryptophan decarboxylase, 154.3 +/- 14.3 mg/L of serotonin was produced.
      Conclusions: We present results of a two-stage fermentation process for the
      production of 5HTP and serotonin. The first strain is a highly efficient 5HTP
      producer, and after fermentation the supernatant is separated and used for the
      production of serotonin. This is the first report for the microbial production of
      serotonin from glucose.

PMID- 29568329
TI  - Differential immunological profiles herald magnetic resonance imaging-defined
      perioperative cerebral infarction.
AB  - Background: The perioperative period is associated with a high risk for human
      ischaemic stroke. Although inflammatory mechanisms are known to have an important
      role in cerebral infarction in the nonoperative setting, their role in modulating
      perioperative risk remains unclear. Methods: In this prospective case-control
      study, we compared 10 patients (cases) who developed magnetic resonance imaging
      (MRI) evidence of cerebral infarction following transcatheter aortic valve
      implantation with 10 patients (controls) who underwent the same procedure without
      neurological complication. Blood sampling was performed preoperatively (baseline)
      and at 24 h, 48 h and 72 h postoperatively and analysed for specific cytokines,
      chemokines and complement factors. Results: Baseline serum assessments identified
      significant differences between the two cohorts for levels of complement C3,
      complement C4b, granulocyte-macrophage colony-stimulating factor, interleukin-15
      and macrophage inflammatory protein-1beta. Longitudinal regression analysis and
      best-fit polynomial curves of postoperative analyte profiles identified
      significantly higher levels of complement C3 and matrix metalloproteinase-9, and
      lower levels of interferon-gamma and macrophage inflammatory protein-1beta levels
      in cases versus controls. Conclusions: These results support a potentially
      important role for inflammatory mechanisms in MRI-defined perioperative stroke
      and reveal a potentially important role for complement components in this
      process.

PMID- 29568330
TI  - Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized
      controlled trials.
AB  - Background: Vitamins are essential micronutrients with antioxidant potential that
      may provide a complementary treatment for patients with chronic diseases. Our aim
      was to assess the effect of vitamin supplementation on the antioxidant status and
      glycemic index of type 2 diabetes mellitus patients. Methods: We performed a
      systematic review with meta-analyses. Electronic searches were conducted in
      PubMed, Scopus, and Web of Science (December 2017). Randomized controlled trials
      evaluating the effect of any vitamin or vitamin complex supplementation on
      antioxidant status as primary outcome were included. The outcomes considered
      were: reduction of malondialdehyde (MDA); augmentation of glutathione peroxidase
      (GPx); changes in total antioxidant capacity (TAC), enhance in superoxide
      dismutase enzyme-SOD, and thiobarbituric acid reactive substances (TBARS).
      Outcomes of glycemic control were also evaluated. Pairwise meta-analyses were
      performed using software Review Manager 5.3. Results: Thirty trials fulfilled the
      inclusion criteria, but only 12 could be included in the meta-analyses of
      antioxidant outcomes. The most commonly studied vitamins were B, C, D and E.
      Vitamin E was related to significant reduction of blood glucose as well as
      glycated hemoglobin compared to placebo, while both vitamins C and E were mainly
      associated with reducing MDA and TBARS and elevating GPx, SOD and TAC, compared
      to placebo. However, outcome reports in this field are still inconsistent (e.g.
      because of a lack of standard measures). Conclusions: Supplementation of vitamin
      E may be a valuable strategy for controlling diabetes complications and enhancing
      antioxidant capacity. The effects of other micronutrients should be further
      investigated in larger and well-designed trials to properly place these
      complementary therapies in clinical practice.

PMID- 29568331
TI  - Impact of diabetes mellitus on ischemic cardiomyopathy. Five-year follow-up.
      REVISION-DM trial.
AB  - Background: Patients with ischemic cardiomyopathy and severe left ventricular
      dysfunction have a worse survival prognosis than patients with preserved
      ventricular function. The role of diabetes in the long-term prognosis of this
      patient group is unknown. This study investigated whether the presence of
      diabetes has a long-term impact on left ventricular function. Methods: Patients
      with coronary artery disease who underwent coronary artery bypass graft surgery,
      percutaneous coronary intervention, or medical therapy alone were included. All
      patients had multivessel disease and left ventricular ejection fraction
      measurements. Overall mortality, nonfatal myocardial infarction, stroke, and
      additional interventions were investigated. Results: From January 2009 to January
      2010, 918 consecutive patients were selected and followed until May 2015. They
      were separated into 4 groups: G1, 266 patients with diabetes and ventricular
      dysfunction; G2, 213 patients with diabetes without ventricular dysfunction; G3,
      213 patients without diabetes and ventricular dysfunction; and G4, 226 patients
      without diabetes but with ventricular dysfunction. Groups 1, 2, 3, and 4,
      respectively, had a mortality rate of 21.6, 6.1, 4.2, and 10.6% (P < .001);
      nonfatal myocardial infarction of 5.3, .5, 7.0, and 2.6% (P < .001); stroke of
      .40, .45, .90, and .90% (P = NS); and additional intervention of 3.8, 11.7, 10.3,
      and 2.6% (P < .001). Conclusion: In this sample, regardless of the treatment
      previously received patients with or without diabetes and preserved ventricular
      function experienced similar outcomes. However, patients with ventricular
      dysfunction had a worse prognosis compared with those with normal ventricular
      function; patients with diabetes had greater mortality than patients without
      diabetes.Trial registration http://www.controlled-trials.com. Registration
      Number: ISRCTN66068876.

PMID- 29568332
TI  - The association between body mass index and health and economic outcomes in
      Brazil.
AB  - Background: Obesity is associated with significant physical, psychosocial and
      economic burden globally. In Brazil, almost 50% of the population is either
      overweight or obese. The prevalence of morbid obesity increased by 255% between
      1975 and 2003. The current study sought to quantify the relationship between
      weight status and health outcomes. Methods: Data from three waves (2011, 2012,
      and 2015) of the Brazil National Health and Wellness Survey, an Internet-based
      survey administered to a demographically diverse sample of Brazilian adults, were
      used. Body mass index category was calculated based on self-reported height and
      weight and respondents were categorized into five groups (normal, overweight,
      obese class I, obese class II, obese class III; n = 34,254). Multivariable
      analyses, controlling for sociodemographic variables and health history, tested
      the association with body mass index group and outcomes including health status
      (Medical Outcomes Study Short Form 12-Item Health Survey version 2/Medical
      Outcomes Study Short Form 36-Item Health Survey version 2), work productivity
      (Work Productivity and Activity Impairment-General Health Questionnaire), and
      costs associated with work impairment (indirect costs), self-reported healthcare
      resource use and associated direct costs. Results: Overall, 53.6% of the surveyed
      Brazilian population reported being overweight or obese. In virtually all the
      analyses, increasing body mass index group was associated with significant and
      progressively worse outcomes. Most notable was the finding that hospitalization
      costs were over twice as high (R$3141.84 vs. R$1349.60) and indirect costs were
      nearly double (R$1656.80 vs. R$884.15) for obesity class III than for normal body
      mass index respondents. Conclusions: Obesity rates in Brazil are considerable
      and, from a patient and societal perspective, increasingly burdensome, thereby
      highlighting the need for stakeholders to prioritize strategies for weight
      management interventions.

PMID- 29568333
TI  - Relationship between "a body shape index (ABSI)" and body composition in obese
      patients with type 2 diabetes.
AB  - Background: Obesity is known to be related to the development of type 2 diabetes
      mellitus (T2D). The most commonly used anthropometric indicator (body mass index
      [BMI]) presents several limitations such as the lack of possibility to
      distinguish adipose tissue distribution. Thus, this study examines the
      suitability of a body shape index (ABSI) for prediction of body composition and
      sarcopenic obesity in obese or overweight T2D subjects. Methods: Cross-sectional
      study in 199 overweight/obese T2D adults. Anthropometric (BMI, ABSI) and body
      composition (fat mass [FM], fat-free mass [FFM], fat mass index [FMI] and fat
      free mass index, and the ratio FM/FFM as an index of sarcopenic obesity) data was
      collected, as well as metabolic parameters (glycated haemoglobin [HbA1c], mean
      blood glucose, fasting plasma glucose [FPG], high-density-lipoprotein cholesterol
      [HDL], low-density-lipoprotein cholesterol, total cholesterol, and triglycerides
      [TG] levels; the ratio TG/HDL was also calculated as a surrogate marker for
      insulin resistance). Results: ABSI was significantly associated with age and
      waist circumference. It showed a statistically significant correlation with BMI
      exclusively in women. Regarding body composition, in men, ABSI was associated
      with FM (%), while in women it was associated with both FM and FFM. Both males
      and females groups with high ABSI scores were significantly older (men: 59.3 +/-
      10.8 vs 54.6 +/- 10.1, p <= 0.05; women: 65.1 +/- 9.8 vs 58.1 +/- 13.3, p <=
      0.005) and showed lower FFM values (men: 62.3 +/- 9.0 vs 66.2 +/- 9.3, p <= 0.05;
      women: 48.7 +/- 5.6 vs 54.5 +/- 8.9, p <= 0.001) compared with low-ABSI groups.
      Multiple linear regression revealed that ABSI independently predict FMI and the
      FM/FFM ratio in women. Sarcopenic obesity was identified in 70 (36.5%)
      individuals according to the FM/FFM ratio. The AUROC of ABSI was 63.1% (95% CI
      54.6-71.6%; p = 0.003) and an ABSI value of 0.083 m11/6 kg-2/3 was the optimal
      threshold in discriminating patients with sarcopenic obesity (sensitivity: 48%,
      specificity: 73%). Moreover, a significant association between ABSI and FPG was
      found in men. Conclusions: ABSI could be useful to identify visceral and
      sarcopenic obesity in overweight/obese adults with T2D, adding some relevant
      clinical information to traditional anthropometric measures.

PMID- 29568334
TI  - Serum uric acid and renal function in patients with type 1 diabetes: a nationwide
      study in Brazil.
AB  - Background: Diabetes nephropathy is a microvascular complication associated with
      high morbidity and mortality in patients with type 1 diabetes, and its
      pathogenesis is not fully understood. Our aim was to evaluate the association
      between levels of serum uric acid and renal function assessed by glomerular
      filtration rate (GFR) and albuminuria in patients with type 1 diabetes. Methods:
      This is a multicenter, cross-sectional, observational study with 1686 patients,
      conducted between August 2011 and August 2014 in 14 public clinics from ten
      Brazilian cities. Renal function was estimated by CKD-EPI (adults) and by
      Schwartz (adolescents). Results: We analyzed 1686 patients, aged 30.1 +/- 12.0,
      with 15.4 +/- 9.3 years of duration of diabetes; 55.8% were female and 54.0% were
      Caucasians. Serum uric acid was related to renal function, with a mean of 4.8 +/-
      1.4 (in the normal renal function group) vs 5.2 +/- 2.0 (GFR >= 60 ml/min and
      albuminuria) vs 6.5 +/- 2.6 mg/dl (GFR < 60 ml/min). In the pooled group,
      multivariate analysis showed an inverse correlation between serum uric acid and
      GFR (r = - 0.316, p < 0.001) with a decrease of 4.11 ml/min in the GFR for every
      increase of 1 mg/dl in serum uric acid. Considering only patients with normal
      renal function (n = 1170), a decrease of 2.04 ml/min in the GFR for every
      increase of 1 mg/dl in Serum uric acid was noted using multivariate analysis.
      Conclusions: Patients with higher levels of serum uric acid have worse renal
      function, independently of HbA1c or duration of diabetes, which persisted even in
      patients with normal renal function. Further prospective studies are necessary to
      establish if patients with higher serum uric acid may have an elevated risk for
      developing chronic kidney disease.

PMID- 29568335
TI  - Paper Spray Mass Spectrometry for High-Throughput Quantification of Nicotine and
      Cotinine.
AB  - The rapid release of new tobacco products requires high-throughput quantitative
      methods to support tobacco research. Sample preparation for LC-MS and GC-MS is
      time consuming and limits throughput. Paper spray tandem mass spectrometry (PS
      MS/MS) is proposed and validated as a simple and rapid method for quantification
      of nicotine and cotinine in complex matrices to support tobacco-related research.
      Air liquid interface (ALI) human tracheobronchial epithelial cell (HTBEC)
      cultures were exposed to tobacco smoke using a Vitrocell VC-10 smoking machine.
      Apical culture washes (phosphate buffered saline, PBS) and basolateral media were
      analyzed with the PS-MS/MS method. GC-MS/MS was used as a comparative
      quantitative technique. The PS-MS/MS approach allowed for direct spotting of
      samples on the paper substrate, whereas the GC-MS/MS method required additional
      sample preparation in the form of solvent-solvent extraction. Limits of
      quantitation (LOQs) were higher with the PS-MS/MS approach than GC-MS/MS, but
      still below the relevant concentrations found in HTBEC smoke exposure experiments
      as well as most clinical applications. PS-MS/MS is readily achieved on mass
      spectrometers that include atmospheric pressure inlets, and allows for convenient
      quantification from complex matrices that would otherwise require additional
      sample preparation and chromatographic separation.

PMID- 29568336
TI  - Testing the single-pass VOC removal efficiency of an active green wall using
      methyl ethyl ketone (MEK).
AB  - In recent years, research into the efficacy of indoor air biofiltration
      mechanisms, notably living green walls, has become more prevalent. Whilst green
      walls are often utilised within the built environment for their biophilic
      effects, there is little evidence demonstrating the efficacy of active green wall
      biofiltration for the removal of volatile organic compounds (VOCs) at
      concentrations found within an interior environment. The current work describes a
      novel approach to quantifying the VOC removal effectiveness by an active living
      green wall, which uses a mechanical system to force air through the substrate and
      plant foliage. After developing a single-pass efficiency protocol to understand
      the immediate effects of the system, the active green wall was installed into a
      30-m3 chamber representative of a single room and presented with the contaminant
      2-butanone (methyl ethyl ketone; MEK), a VOC commonly found in interior
      environments through its use in textile and plastic manufacture. Chamber inlet
      levels of MEK remained steady at 33.91 +/- 0.541 ppbv. Utilising a forced-air
      system to draw the contaminated air through a green wall based on a soil-less
      growing medium containing activated carbon, the combined effects of substrate
      media and botanical component within the biofiltration system showed
      statistically significant VOC reduction, averaging 57% single-pass removal
      efficiency over multiple test procedures. These results indicate a high level of
      VOC removal efficiency for the active green wall biofilter tested and provide
      evidence that active biofiltration may aid in reducing exposure to VOCs in the
      indoor environment.

PMID- 29568337
TI  - Evaluation of daily time spent in transportation and traffic-influenced
      microenvironments by urban Canadians.
AB  - Exposure to traffic and traffic-related air pollution is associated with a wide
      array of health effects. Time spent in a vehicle, in active transportation, along
      roadsides, and in close proximity to traffic can substantially contribute to
      daily exposure to air pollutants. For this study, we evaluated daily time spent
      in transportation and traffic-influenced microenvironments by urban Canadians
      using the Canadian Human Activity Pattern Survey (CHAPS) 2 results. Approximately
      4-7% of daily time was spent in on- or near-road locations, mainly associated
      with being in a vehicle and smaller contributions from active transportation.
      Indoor microenvironments can be impacted by traffic emissions, especially when
      located near major roadways. Over 60% of the target population reported living
      within one block of a roadway with moderate to heavy traffic, which was variable
      with income level and city, and confirmed based on elevated NO2 exposure
      estimated using land use regression. Furthermore, over 55% of the target
      population <= 18 years reported attending a school or daycare in close proximity
      to moderate to heavy traffic, and little variation was observed based on income
      or city. The results underline the importance of traffic emissions as a major
      source of exposure in Canadian urban centers, given the time spent in traffic
      influenced microenvironments.

PMID- 29568338
TI  - Daily land use regression estimated woodsmoke and traffic pollution
      concentrations and the triggering of ST-elevation myocardial infarction: a case
      crossover study.
AB  - Prior work has reported acute associations between ST-elevation myocardial
      infarction (STEMI) and short-term increases in airborne particulate matter.
      Subsequently, the association between STEMI and hourly measures of Delta-C
      (marker of woodsmoke) and black carbon (marker of traffic pollution) measured at
      a central site in Rochester, NY, were examined, but no association was found.
      Therefore, land use regression estimates of Delta-C and black carbon
      concentrations at each patient's residence were developed for 246 STEMI patients
      treated at the University of Rochester Medical Center during the winters of 2008
      2012. Using case-crossover methods, the rate of STEMI associated with increased
      Delta-C and BC concentration on the same and previous 3 days was estimated after
      adjusting for 3-day mean temperature and relative humidity. Non-statistically
      significant increased rates of STEMI associated with interquartile range
      increases in concentrations of BC in the previous 2 days (1.10 MUg/m3; OR = 1.12;
      95% CI 0.93, 1.35) and Delta-C in the previous 3 days (0.43 MUg/m3; OR = 1.16;
      95% CI 0.96, 1.40) were found. Significantly increased rates of STEMI associated
      with interquartile range increases in concentrations of BC (1.23 MUg/m3; OR =
      1.04; 95% CI = 0.87, 1.24) or Delta-C (0.40 MUg/m3; OR = 0.94; 95% CI = 0.85,
      1.09) on the same day were not observed likely due, in part, to temporal
      misalignment. Therefore, sophisticated spatial-temporal models will be needed to
      minimize exposure error and bias by better predicting concentrations at
      individual locations for individual hours, especially for outcomes with short
      term responses to air pollution (< 24 h).

PMID- 29568340
TI  - General Considerations for Improving Photovoltage in Metal-Insulator
      Semiconductor Photoanodes.
AB  - Metal-insulator-semiconductor (MIS) photoelectrodes offer a simple alternative to
      the traditional semiconductor-liquid junction and the conventional p-n junction
      electrode. Highly efficient MIS photoanodes require interfacial surface
      passivating oxides and high workfunction metals to produce a high photovoltage.
      Herein, we investigate and analyze the effect of interfacial oxides and metal
      workfunctions on the barrier height and the photovoltage of a c-Si photoanode. We
      use two metal components in a bimetal contact configuration and observe the
      modulation of the effective barrier height and the resulting photovoltage as a
      function of the secondary outer metal. The photovoltage shows a strong linear
      dependence by increasing the inner metal workfunction, with the highest
      photovoltage achieved by a MIS photoanode using a platinum inner metal. We also
      found that coupling a thin aluminium oxide with an interfacial silicon oxide and
      controlling the oxide thickness can significantly improve the photovoltage of an
      MIS junction photoanode.

PMID- 29568341
TI  - Structural Characterization of Electron Donors in Ziegler-Natta Catalysts.
AB  - Ziegler-Natta catalysis is a very important industrial process for the production
      of polyolefins. However, the catalysts are not well-understood at the molecular
      level. Yet, atomic-scale structural information is of pivotal importance for
      rational catalyst development. We applied a solid-state NMR/density functional
      theory tandem approach to gain detailed insight into the interactions between the
      catalysts' support, MgCl2, and organic electron donors. Because of the
      heterogeneity of the samples, large line widths are observed in the carbon
      spectra. Despite this, good agreement between experimental and computational
      values was reached, and this shows that 1,3-diether based donors coordinate at
      (110) surface sites, while phthalates are less selective and coordinate at both
      (104) and (110) surface sites.

PMID- 29568339
TI  - Repetitive Transcranial Magnetic Stimulation, Cognition, and Multiple Sclerosis:
      An Overview.
AB  - Multiple sclerosis (MS) affects cognition in the majority of patients. A major
      aspect of the disease is brain volume loss (BVL), present in all phases and types
      (relapsing and progressive) of the disease and linked to both motor and cognitive
      disabilities. Due to the lack of effective pharmacological treatments for
      cognition, cognitive rehabilitation and other nonpharmacological interventions
      such as repetitive transcranial magnetic stimulation (rTMS) have recently emerged
      and their potential role in functional connectivity is studied. With recently
      developed advanced neuroimaging and neurophysiological techniques, changes
      related to alterations of the brain's functional connectivity can be detected. In
      this overview, we focus on the brain's functional reorganization in MS,
      theoretical and practical aspects of rTMS utilization in humans, and its
      potential therapeutic role in treating cognitively impaired MS patients.

PMID- 29568342
TI  - Smoking, environmental tobacco smoke and occupational irritants increase the risk
      of chronic rhinitis.
AB  - Background: Allergic and non-allergic rhinitis cause a lot of symptoms in
      everyday life. To decrease the burden more information of the preventable risk
      factors is needed. We assessed prevalence and risk factors for chronic nasal
      symptoms, exploring the effects of smoking, environmental tobacco smoke, exposure
      to occupational irritants, and their combinations. Methods: In 2016, a postal
      survey was conducted among a random population sample of 8000 adults in Helsinki,
      Finland with a 50.5% response rate. Results: Smoking was associated with a
      significant increase in occurrence of chronic rhinitis (longstanding nasal
      congestion or runny nose), but not with self-reported or physician diagnosed
      allergic rhinitis. The highest prevalence estimates of nasal symptoms, 55.1% for
      chronic rhinitis, 49.1% for nasal congestion, and 40.7% for runny nose, were
      found among smokers with occupational exposure to gases, fumes or dusts.Besides
      active smoking, also exposure to environmental tobacco smoke combined with
      occupational exposure increased the risk of nasal symptoms. Conclusions: Smoking,
      environmental tobacco smoke, and occupational irritants are significant risk
      factors for nasal symptoms with an additive pattern. The findings suggest that
      these factors should be systematically inquired in patients with nasal symptoms
      for appropriate preventive measures. (192 words).

PMID- 29568343
TI  - The SRC-family tyrosine kinase HCK shapes the landscape of SKAP2 interactome.
AB  - The SRC Kinase Adaptor Phosphoprotein 2 (SKAP2) is a broadly expressed adaptor
      associated with the control of actin-polymerization, cell migration, and
      oncogenesis. After activation of different receptors at the cell surface, this
      dimeric protein serves as a platform for assembling other adaptors such as FYB
      and some SRC family kinase members, although these mechanisms are still poorly
      understood. The goal of this study is to map the SKAP2 interactome and
      characterize which domains or binding motifs are involved in these interactions.
      This is a prerequisite to finely analyze how these pathways are integrated in the
      cell machinery and to study their role in cancer and other human diseases when
      this network of interactions is perturbed. In this work, the domain and the
      binding motif of fourteen proteins interacting with SKAP2 were precisely defined
      and a new interactor, FAM102A was discovered. Herein, a fine-tuning between the
      binding of SRC kinases and their activation was identified. This last process,
      which depends on SKAP2 dimerization, indirectly affects the binding of FYB
      protein. Analysis of conformational changes associated with activation/inhibition
      of SRC family members, presently limited to their effect on kinase activity, is
      extended to their interactive network, which paves the way for therapeutic
      development.

PMID- 29568344
TI  - Correlation and agreement between eplet mismatches calculated using serological,
      low-intermediate and high resolution molecular human leukocyte antigen typing
      methods.
AB  - Structural human leukocyte antigen (HLA) matching at the eplet level can be
      identified by HLAMatchmaker, which requires the entry of four-digit alleles. The
      aim of this study was to evaluate the agreement between eplet mismatches
      calculated by serological and two-digit typing methods compared to high
      resolution four-digit typing. In a cohort of 264 donor/recipient pairs, the
      evaluation of measurement error was assessed using intra-class correlation to
      confirm the absolute agreement between the number of eplet mismatches at class I
      (HLA-A, -B, C) and II loci (HLA-DQ and -DR) calculated using serological or two
      digit molecular typing compared to four-digit molecular typing methods. The
      proportion of donor/recipient pairs with a difference of >5 eplet mismatches
      between the HLA typing methods was also determined. Intra-class correlation
      coefficients between serological and four-digit molecular typing methods were
      0.969 (95% confidence intervals [95% CI] 0.960-0.975) and 0.926 (95% CI 0.899
      0.944), respectively; and 0.995 (95% CI 0.994-0.996) and 0.993 (95% CI 0.991
      0.995), respectively between two-digit and four-digit molecular typing methods.
      The proportion of donor/recipient pairs with a difference of >5 eplet mismatches
      at class I and II loci was 4% and 16% for serological versus four-digit molecular
      typing methods, and 0% and 2% for two-digit versus four-digit molecular typing
      methods, respectively. In this small predominantly Caucasian population, compared
      with serology, there is a high level of agreement in the number of eplet
      mismatches calculated using two-compared to four-digit molecular HLA-typing
      methods, suggesting that two-digit typing may be sufficient in determining eplet
      mismatch load in kidney transplantation.

PMID- 29568345
TI  - IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid
      oxidation-dependent manner.
AB  - T-cell-based therapies represent a promising strategy for cancer treatment. In
      this context, cytokines are discussed as a bona fide instrument for fine-tuning T
      cell biology. One promising candidate is the pleiotropic interleukin-21 (IL-21)
      with only little being known regarding its direct effects on human T-cells. Thus,
      we sought out to characterize the impact of IL-21 on T-cell metabolism, fitness,
      and differentiation. Culturing T-cells in presence of IL-21 elicited a metabolic
      skewing away from aerobic glycolysis towards fatty acid oxidation (FAO). These
      changes of the metabolic framework were paralleled by increased mitochondrial
      fitness and biogenesis. However, oxidative stress levels were not increased but
      rather decreased. Furthermore, elevated FAO and mitochondrial biomass together
      with enhanced antioxidative properties are linked to formation of longer lasting
      memory responses and less PD-1 expression. We similarly observed an IL-21
      triggered induction of central memory-like T-cells and reduced levels of PD-1 on
      the cell surface. Taken together, IL-21 shifts T-cells towards an immunometabolic
      phenotype that has been associated with increased survivability and enhanced anti
      tumor efficacy. In addition, our data reveals a novel interconnection between
      fatty acid metabolism and immune function regulated by IL 21.

PMID- 29568346
TI  - Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for
      fragment-based drug discovery in PHGDH-amplified breast cancer.
AB  - 3-Phosphoglycerate dehydrogenase (PHGDH) has recently been identified as an
      attractive target in cancer therapy as it links upregulated glycolytic flux to
      increased biomass production in cancer cells. PHGDH catalyses the first step in
      the serine synthesis pathway and thus diverts glycolytic flux into serine
      synthesis. We have used siRNA-mediated suppression of PHGDH expression to show
      that PHGDH is a potential therapeutic target in PHGDH-amplified breast cancer.
      Knockdown caused reduced proliferation in the PHGDH-amplified cell line MDA-MB
      468, whereas breast cancer cells with low PHGDH expression or with elevated PHGDH
      expression in the absence of genomic amplification were not affected. As a first
      step towards design of a chemical probe for PHGDH, we report a fragment-based
      drug discovery approach for the identification of PHGDH inhibitors. We designed a
      truncated PHGDH construct that gave crystals which diffracted to high resolution,
      and could be used for fragment soaking. 15 fragments stabilising PHGDH were
      identified using a thermal shift assay and validated by X-ray crystallography and
      ITC competition experiments to exhibit 1.5-26.2 mM affinity for PHGDH. A
      structure-guided fragment growing approach was applied to the PHGDH binders from
      the initial screen, yielding greater understanding of the binding site and
      suggesting routes to achieve higher affinity NAD-competitive inhibitors.

PMID- 29568347
TI  - Targeting DYRK1B suppresses the proliferation and migration of liposarcoma cells.
AB  - Liposarcoma is a common subtype of soft tissue sarcoma and accounts for 20% of
      all sarcomas. Conventional chemotherapeutic agents have limited efficacy in
      liposarcoma patients. Expression and activation of serine/threonine-protein
      kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B (DYRK1B)
      is associated with growth and survival of many types of cancer cells. However,
      the role of DYRK1B in liposarcoma remains unknown. In this study, we investigated
      the functional and therapeutic relevance of DYRK1B in liposarcoma. Tissue
      microarray and immunohistochemistry analysis showed that higher expression levels
      of DYRK1B correlated with a worse prognosis. RNA interference-mediated knockdown
      of DYRK1B or targeting DYRK1B with the kinase inhibitor AZ191 inhibited
      liposarcoma cell growth, decreased cell motility, and induced apoptosis.
      Moreover, combined AZ191 with doxorubicin demonstrated an increased anti-cancer
      effect on liposarcoma cells. These findings suggest that DYRK1B is critical for
      the growth of liposarcoma cells. Targeting DYRK1B provides a new rationale for
      treatment of liposarcoma.

PMID- 29568348
TI  - Phthalate exposure promotes chemotherapeutic drug resistance in colon cancer
      cells.
AB  - Phthalates are widely used as plasticizers. Humans can be exposed to phthalates
      through ingestion, inhalation, or treatments that release di(2-ethylhexyl)
      phthalate (DEHP) and its metabolite, mono(2-ehylhexyl) phthalate (MEHP), into the
      body from polyvinyl chloride-based medical devices. Phthalate exposure may induce
      reproductive toxicity, liver damage, and carcinogenesis in humans. This study
      found that colon cancer cells exposed to DEHP or MEHP exhibited increased cell
      viability and increased levels of P-glycoprotein, CD133, Bcl-2, Akt, ERK,
      GSK3beta, and beta-catenin when treated with oxaliplatin or irinotecan, as
      compared to control. The P-glycoprotein inhibitor, tariquidar, which blocks drug
      efflux, reduced the viability of DEHP- or MEHP-treated, anti-cancer drug
      challenged cells. DEHP or MEHP treatment also induced colon cancer cell migration
      and epithelial-mesenchymal transformation. Elevated stemness-related protein
      levels (beta-catenin, Oct4, Sox2, and Nanog) and increased cell sphere sizes
      indicated that DEHP- or MEHP-treated cells were capable of self-renewal. We also
      found that serum DEHP concentrations were positively correlated with cancer
      recurrence. These results suggest phthalate exposure enhances colon cancer cell
      metastasis and chemotherapeutic drug resistance by increasing cancer cell
      stemness, and that P-glycoprotein inhibitors might improve outcomes for advanced
      or drug-resistant colon cancer patients.

PMID- 29568349
TI  - Exploring the pathogenesis of canine epilepsy using a systems genetics method and
      implications for anti-epilepsy drug discovery.
AB  - Epilepsy is a common neurological disorder in domestic dogs. However, its complex
      mechanism involves multiple genetic and environmental factors that make it
      challenging to identify the real pathogenic factors contributing to epilepsy,
      particularly for idiopathic epilepsy. Conventional genome-wide association
      studies (GWASs) can detect various genes associated with epilepsy, although they
      primarily detect the effects of single-site mutations in epilepsy while ignoring
      their interactions. In this study, we used a systems genetics method combining
      both GWAS and gene interactions and obtained 26 significantly mutated
      subnetworks. Among these subnetworks, seven genes were reported to be involved in
      neurological disorders. Combined with gene ontology enrichment analysis, we
      focused on 4 subnetworks that included traditional GWAS-neglected genes.
      Moreover, we performed a drug enrichment analysis for each subnetwork and
      identified significantly enriched candidate anti-epilepsy drugs using a
      hypergeometric test. We discovered 22 potential drug combinations that induced
      possible synergistic effects for epilepsy treatment, and one of these drug
      combinations has been confirmed in the Drug Combination database (DCDB) to have
      beneficial anti-epileptic effects. The method proposed in this study provides
      deep insight into the pathogenesis of canine epilepsy and implications for anti
      epilepsy drug discovery.

PMID- 29568350
TI  - EIF3C-enhanced exosome secretion promotes angiogenesis and tumorigenesis of human
      hepatocellular carcinoma.
AB  - Targeting tumor angiogenesis is a common strategy against human hepatocellular
      carcinoma (HCC). However, identification of molecular targets as biomarker for
      elevating therapeutic efficacy is critical to prolong HCC patient survival. Here,
      we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is
      upregulated during HCC tumor progression and associated with poor patient
      survival. Expression of EIF3C did not alter proliferation and expression of other
      tumor progressive genes such as HIF1A, TGFbeta1 and VEGF, but reduced cell
      migration in HCC cells. Nevertheless, expression of EIF3C in HCC cells
      significantly increase secretion of extracellular exosomes confirmed by increased
      exosomes labelling by PKH26 fluorescent dye, vesicles in exosome size detected by
      electronic microscopy and nanoparticle tracking analysis, and expression of
      divergent exosome markers. The EIF3C-increased exosomes were oncogenic to
      potentiate tumor angiogenesis via tube formation of HUVEC cells and growth of
      vessels by plugs assays on nude mice. Subcutaneous inoculation of EIF3C-exosomes
      mixed with Huh7 HCC cells not only promoted growth of vessels but also increased
      expression of EIF3C in tumors. Conversely, treatment of exosome inhibitor GW4869
      reversed aforementioned oncogenic assays. We identified EIF3C activated
      expression of S100A11 involved in EIF3C-exosome increased tube formation in
      angiogenesis. Simultaneous high expression of EIF3C and S100A11 in human HCC
      tumors for RNA level in TCGA and protein level by IHC are associated with poor
      survival of HCC patients. Collectively, our results demonstrated that EIF3C
      overexpression is a potential target of angiogenesis for treatment with exosome
      inhibitor or S100A11 reduction to suppress HCC angiogenesis and tumorigenesis.

PMID- 29568351
TI  - Targeting of embryonic annexin A2 expressed on ovarian and breast cancer by the
      novel monoclonal antibody 2448.
AB  - Monoclonal antibodies (mAbs) play an increasingly important role in cancer
      therapy. To address the wide heterogeneity of the disease, the identification of
      novel antigen targets and the development of mAbs against them are needed. Our
      lab previously generated a panel of mAbs against human embryonic stem cells
      (hESC) using a whole cell immunization approach in mice. These mAbs can
      potentially target oncofetal antigens and be repurposed for antibody or antibody
      drug conjugate (ADC) therapy. From this panel, the novel IgG1 2448 was found to
      bind surface antigens on hESC and multiple cancer cell lines. Here, we show 2448
      targets a unique glycan epitope on annexin A2 (ANXA2) and can potentially monitor
      the Epithelial-Mesenchymal Transition (EMT) in ovarian and breast cancer. To
      evaluate 2448 as a potential drug, 2448 was engineered and expressed as a
      chimeric IgG1. Chimeric 2448 (ch2448) demonstrated efficient and specific killing
      when conjugated to cytotoxic payloads as an ADC. In addition, ch2448 elicited
      potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro and
      in vivo. Further engineering of ch2448 to remove fucose in the Fc domain enhanced
      ADCC. Overall, these findings indicate that embryonic ANXA2 is an attractive
      target and suggest that ch2448 is a promising candidate for further therapeutic
      development.

PMID- 29568352
TI  - The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with
      hepatocellular carcinoma.
AB  - Previous studies showed that the low expressions of chromodomain-helicase-DNA
      binding protein 5 (CHD5) were intensively associated with deteriorative biologic
      and clinical characteristics as well as outcomes in many tumors. The aim of this
      study is to determine whether CHD5 single nucleotide polymorphisms (SNPs)
      contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were
      selected according to their linkage disequilibrium (LD) in the targeted next
      generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a
      rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated
      with HCC prognosis. The univariate and multivariate regression analyses revealed
      the patients with worse overall survival time were those with tumor metastasis
      and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage.
      Based on the available public databases, we discovered the significant
      association between haplotype AG and CHD5 mRNA expressions only existed in
      Chinese. These data proposed that the potentially genetic haplotype might
      functionally contribute to HCC prognosis and CHD5 mRNA expressions.

PMID- 29568353
TI  - Reprogrammed lipid metabolism in bladder cancer with cisplatin resistance.
AB  - Due to its tendency to recur and acquire chemoresistance quickly, bladder cancer
      (BC) remains to be an elusive and difficult disease. Patients with recurrent and
      chemoresistant BC have an extremely poor prognosis. One possible approach that
      may provide insightful and valuable information regarding resistance mechanisms
      is looking into the lipid metabolism of BC cells. Metabolism of lipids is
      essential for cancer cells and is associated with the regulation of a variety of
      key cellular processes and functions. This study conducted a comparative
      lipidomic profiling of two isogenic human T24 bladder cancer cell lines, one of
      which is clinically characterized as cisplatin-sensitive (T24S) and the other as
      cisplatin-resistant (T24R). Immunohistochemistry analysis revealed that
      expression of cytosolic acetyl-CoA synthetase 2 (ACSS2) is positively correlated
      with aggressive BC. Ultra performance liquid chromatography-mass spectrometry
      (UPLC-MS) analysis profiled a total of 1,864 lipids and levels of differentially
      expressed lipids suspected of being associated with cisplatin resistance were
      determined. In addition, we found that ACSS2 inhibition greatly perturbed levels
      of metabolites, including CE(18:1), CE(22:6), TG(49:1), and TG(53:2). This study
      broadens our current knowledge on the links between cisplatin resistance and
      lipid metabolism in aggressive BC and suggests potential biomarkers for
      identifying higher-risk patients.

PMID- 29568354
TI  - miR-128 inhibits telomerase activity by targeting TERT mRNA.
AB  - Telomerase is a unique cellular reverse transcriptase (RT) essential for
      maintaining telomere stability and required for the unlimited proliferation of
      cancer cells. The limiting determinant of telomerase activity is the catalytic
      component TERT, and TERT expression is closely correlated with telomerase
      activity and cancer initiation and disease progression. For this reason the
      regulation of TERT levels in the cell is of great importance. microRNAs (miRs)
      function as an additional regulatory level in cells, crucial for defining
      expression boundaries, proper cell fate decisions, cell cycle control, genome
      integrity, cell death and metastasis. We performed an anti-miR library screen to
      identity novel miRs, which participate in the control of telomerase. We
      identified the tumor suppressor miR (miR-128) as a novel endogenous telomerase
      inhibitor and determined that miR-128 significantly reduces the mRNA and protein
      levels of Tert in a panel of cancer cell lines. We further evaluated the
      mechanism by which miR-128 regulates TERT and demonstrated that miR-128 interacts
      directly with the coding sequence of TERT mRNA in both HeLa cells and teratoma
      cells. Interestingly, the functional miR-128 binding site in TERT mRNA, is
      conserved between TERT and the other cellular reverse transcriptase encoded by
      Long Interspersed Elements-1 (LINE-1 or L1), which can also contribute to the
      oncogenic phenotype of cancer. This finding supports the novel idea that miRs may
      function in parallel pathways to inhibit tumorigenesis, by regulating a group of
      enzymes (such as RT) by targeting conserved binding sites in the coding region of
      both enzymes.

PMID- 29568355
TI  - Mitochondrial fission as a driver of stemness in tumor cells: mDIVI1 inhibits
      mitochondrial function, cell migration and cancer stem cell (CSC) signalling.
AB  - Mitochondria are dynamic organelles frequently undergoing fission and fusion
      events to maintain their integrity, bioenergetics and spatial distribution, which
      is fundamental to the processes of cell survival. Disruption in mitochondrial
      dynamics plays a role in cancer. Therefore, proteins involved in regulating
      mitochondrial dynamics are potential targets for treatment. mDIVI1 is an
      inhibitor of the mitochondrial fission protein DRP1, which induces i)
      mitochondrial oxidative stress and ii) effectively reduces mitochondrial
      metabolism. We show here that mDIVI1 is able to inhibit 3D tumorsphere forming
      capacity, cell migration and stemness-related signalling in breast cancer cells,
      indicating that mDIVI1 can potentially be used for the therapeutic elimination of
      cancer stem cells (CSCs).

PMID- 29568356
TI  - Neutrophil extracellular traps promote lipopolysaccharide-induced airway
      inflammation and mucus hypersecretion in mice.
AB  - Bacterial lipopolysaccharide (LPS) contributes to airway inflammation and mucus
      hypersecretion in chronic airway inflammatory diseases, such as chronic
      obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Neutrophil
      extracellular traps (NETs) are extracellular meshworks composed of DNA fibers and
      antimicrobial proteins. Although NET formation has been detected in COPD and CF
      patients, how NETs contribute to these diseases is poorly understood. This study
      was performed to clarify the effects and mechanisms of action of NETs in airway
      inflammation and mucus hypersecretion. We created a murine model of LPS-induced
      airway inflammation and mucus hypersecretion, and found that LPS-induced NET
      formation was degraded by aerosolized DNase I treatment in mice. Degradation of
      NETs by aerosolized DNase I reduced LPS-induced airway inflammation and mucus
      hypersecretion in mice, this reduction correlated with suppression of TLR4/NF
      kappaB signaling pathway. More importantly, NETs promoted LPS-induced production
      of IL-1beta, IL-6 and TNF-alpha in macrophages. These results suggest NET
      degradation using aerosolized DNase I is a potential new therapeutic strategy for
      treating COPD and CF.

PMID- 29568357
TI  - Deficiency of protein-L-isoaspartate (D-aspartate) O-methyl-transferase
      expression under endoplasmic reticulum stress promotes epithelial mesenchymal
      transition in lung adenocarcinoma.
AB  - A prognostic association between the novel chaperone protein-L-isoaspartate (D
      aspartate) O-methyltransferase (PIMT) and lung adenocarcinoma has recently been
      reported. Here, we evaluated the functional roles of PIMT in the progression of
      lung adenocarcinoma. PIMT expression was detectable in 6 lung adenocarcinoma cell
      lines: A549, H441, H460, H1650, Calu 1, and Calu 6 cell lines. In A549 and H441
      cells, knockdown by PIMT using silencing RNA of PIMT (si-PIMT) and/or small
      hairpin-RNA (sh-PIMT) induced a decrease in the expression of E-cadherin with an
      increase in vimentin expression, indicating that the epithelial to mesenchymal
      transition (EMT) was induced. Cell mobility, including migration and invasion
      capability, was increased in sh-PIMT A549 stable and si-PIMT H441 cells compared
      to in control cells. Endoplasmic reticulum (ER) stress, such as Thapsigargin (Tg)
      stress and hypoxia, induced EMT in A549 cells but not in other cell types, with
      an increase in GRP78 expression, whereas overexpression of PIMT reduced the EMT
      and cell invasion under stress conditions. The expression of hypoxia inducible
      factor-1 alpha (HIF1alpha) and Twist increased in sh-PIMT A549 and si-PIMT H441
      cells, and Tg stress increased HIF1alpha expression levels in A549 cells in a
      dose-dependent manner. Moreover, LW6, an HIF1alpha inhibitor, reduced EMT, cancer
      invasion, and the levels of Twist in sh-PIMT A549 cells. Our results indicate
      that deficiency of supplemental PIMT expression under ER stress facilitates EMT
      and cell invasion in some cell types of lung adenocarcinoma.

PMID- 29568358
TI  - Systemic administration of a TLR7 agonist attenuates regulatory T cells by
      dendritic cell modification and overcomes resistance to PD-L1 blockade therapy.
AB  - Research on immune checkpoint blockade therapy has made great progress in cancer
      immunotherapy, but the number of patients who benefit from this therapy remains
      limited. In this study, we examined the effects of monotherapy with systemic low
      dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects
      with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and
      Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8+ T
      cell function and accelerated regulatory T cells (Tregs) within the tumors,
      efficiently reduced tumor growth with more recruitment of CD8+ T cells and a
      reduction of Treg. The results of resiquimod monotherapy in Colon 26,
      representing impaired Treg recruitment, were inferior to that in SCCVII. Combined
      resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it
      was associated with reduced tumor size, attenuation of Tregs, and an increased
      ratio of CD8+ T cells/Tregs in both tumors. Systemic administration of low-dose
      resiquimod induced a transient and rapid activation of plasmacytoid and
      conventional dendritic cells, resulting in enhanced priming of T cells in
      regional lymph nodes. Experiments with more limited doses of resiquimod that did
      not yield beneficial effects after single treatment, showed additional effects to
      PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1
      therapy was decreased. Our results suggest that systemic administration of low
      dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy.

PMID- 29568359
TI  - CD151 promotes cell metastasis via activating TGF-beta1/Smad signaling in renal
      cell carcinoma.
AB  - Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated
      in various malignant cell types. However, the function of CD151 and its
      underlying mechanism in renal cell carcinoma is still unknown. In this study, we
      detected the expression of CD151 in RCC cells and tissues and explored its
      regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma
      tissues and cells and its expression was significantly associated with tumor
      stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays. After
      silencing of CD151 via lentivirus vector in Caki-1 and Caki-2 cells, reduced
      ability of migration and invasion were detected with downregulation of CD151. The
      opposite results were observed in cells with CD151 overexpression. Furthermore,
      western blotting was performed to investigate the influence of CD151 on
      epithelial-to-mesenchymal transition, matrix metalloproteinase 9 and TGF
      beta1/Smad signaling pathway in RCC. Subsequently, upregulating the protein level
      of transforming growth factor-beta1 in cells with silencing of CD151 could rescue
      the malignant behaviors inhibited, which indicated that CD151 may play its
      promoting role in RCC partially by stimulating the expression of TGF-beta1.
      Conclusively, CD151 might exhibit a prominent role in migration and invasion of
      RCC cells via activating TGF-beta1/Smad signaling pathway.

PMID- 29568360
TI  - Methotrexate sensitizes drug-resistant metastatic melanoma cells to BRAF V600E
      inhibitors dabrafenib and encorafenib.
AB  - Acquired resistance of metastatic melanoma (MM) tumors to BRAF V600E inhibitors
      (BRAFi's) is commonplace in the clinic. Habitual relapse of patients contributes
      to <20% 5-year survival rates in MM. We previously identified serine synthesis as
      a critical detrminant of late-stage cancer cell resistance to BRAFi's. Pre
      treatment with DNA damaging agent gemcitabine (a nucleoside analog) re-sensitized
      drug-resistant cancer cells to BRAFi's dabrafenib and vemurafenib. Importantly,
      the combination treatments were effective against BRAF wild type cancer cells
      potentially expanding the clinical reach of BRAFi's. In this study, we identify
      the antifolate methotrexate (MTX) as a sensitizer of acquired- and intrinsically
      resistant MM cells to BRAFi's dabrafenib and encorafenib. We identify a novel,
      positive correlation between dabrafenib treatments and repair delay of MTX
      induced single-strand DNA (ssDNA) breaks. Cells arrest in G1 phase following
      simultaneous MTX + dabrafenib treatments and eventually die via apoptosis.
      Importantly, we identify RAS codon 12 activating mutations as prognostic markers
      for MTX + BRAFi treatment efficacy. We describe a method of killing drug
      resistant MM cells that if translated has the potential to improve MM patient
      survival.

PMID- 29568361
TI  - Colorectal cancer cells require glycogen synthase kinase-3beta for sustaining
      mitosis via translocated promoter region (TPR)-dynein interaction.
AB  - Glycogen synthase kinase (GSK) 3beta, which mediates fundamental cellular
      signaling pathways, has emerged as a potential therapeutic target for many types
      of cancer including colorectal cancer (CRC). During mitosis, GSK3beta localizes
      in mitotic spindles and centrosomes, however its function is largely unknown. We
      previously demonstrated that translocated promoter region (TPR, a nuclear pore
      component) and dynein (a molecular motor) cooperatively contribute to mitotic
      spindle formation. Such knowledge encouraged us to investigate putative
      functional interactions among GSK3beta, TPR, and dynein in the mitotic machinery
      of CRC cells. Here, we show that inhibition of GSK3beta attenuated proliferation,
      induced cell cycle arrest at G2/M phase, and increased apoptosis of CRC cells.
      Morphologically, GSK3beta inhibition disrupted chromosome segregation, mitotic
      spindle assembly, and centrosome maturation during mitosis, ultimately resulting
      in mitotic cell death. These changes in CRC cells were associated with decreased
      expression of TPR and dynein, as well as disruption of their functional
      colocalization with GSK3beta in mitotic spindles and centrosomes. Clinically, we
      showed that TPR expression was increased in CRC databases and primary tumors of
      CRC patients. Furthermore, TPR expression in SW480 cells xenografted into mice
      was reduced following treatment with GSK3beta inhibitors. Together, these results
      indicate that GSK3beta sustains steady mitotic processes for proliferation of CRC
      cells via interaction with TPR and dynein, thereby suggesting that the
      therapeutic effect of GSK3beta inhibition depends on induction of mitotic
      catastrophe in CRC cells.

PMID- 29568362
TI  - The metal-nonoate Ni(SalPipNONO) inhibits in vitro tumor growth, invasiveness and
      angiogenesis.
AB  - Nitric oxide (NO) exerts conflicting effect on tumor growth and progression,
      depending on its concentration. We aimed to characterize the anti-cancer activity
      of a new NO donor, Ni(SalPipNONO) belonging to the class of metal-nonoates, in
      epithelial derived tumor cells, finally exploring its antiangiogenic properties.
      Tumor epithelial cells were screened to evaluate the cytotoxic effect of
      Ni(SalPipNONO), which was able to inhibit cell proliferation in a dose dependent
      manner, being more effective than the commercial DETA/NO. The human lung
      carcinoma cells A549 were chosen as model to study the anti-cancer mechanisms
      exerted by the compound. In these cells, Ni(SalPipNONO) inhibited clonogenicity
      and cell invasion, while promoting apoptosis. The antitumor activity was partly
      due to NO-cGMP dependent pathway, contributing to reduced cell number and
      apoptosis, and partly to the salicylaldehyde moiety and reactive oxygen species
      (ROS) activated ERK1/2 signaling converging on p53 dependent caspase-3 cleavage.
      An additional contribution by downstream cycloxygenase-2 (COX-2) derived
      cyclopentenones may explain the tumor inhibitory activities. As NO has been
      described to affect tumor angiogenesis, we checked this activity both on tumor
      and endothelial cell co-cultures and in Matrigel in vivo assay. Our data document
      that Ni(SalPipNONO) was able to both reduce angiogenic factor expression by tumor
      cells acting on hypoxia inducible factor-1alpha (HIF-1 alpha) level, and
      endothelial cell functions related to angiogenesis. Collectively, these data
      confirm the potential use of NO donors and in particular Ni(SalPipNONO) acting
      through multiple mechanisms, as an agent to be further developed to be used alone
      or in combination with conventional therapy.

PMID- 29568363
TI  - Targeting angiogenesis in multiple myeloma by the VEGF and HGF blocking DARPin(r)
      protein MP0250: a preclinical study.
AB  - The investigational drug MP0250 is a multi-specific DARPin(r) molecule that
      simultaneously binds and neutralizes VEGF and HGF with high specificity and
      affinity. Here we studied the antiangiogenic effects of the MP0250 in multiple
      myeloma (MM). In endothelial cells (EC) isolated from bone marrow (BM) of MM
      patients (MMEC) MP0250 reduces VEGFR2 and cMet phosphorylation and affects their
      downstream signaling cascades. MP0250 influences the secretory profile of MMEC
      and inhibits their in vitro angiogenic activities (spontaneous and chemotactic
      migration, adhesion, spreading and capillarogenesis). Compared to anti-VEGF or
      anti-HGF neutralizing mAbs, MP0250 strongly reduces capillary network formation
      and vessel-sprouting in a Matrigel angiogenesis assay. MP0250 potentiates the
      effect of bortezomib in the same in vitro setting. It significantly reduces the
      number of newly formed vessels in the choriollantoic membrane assay (CAM) and the
      Matrigel plug assay. In the syngeneic 5T33MM tumor model, MP0250 decreases the
      microvessel density (MVD) and the combination MP0250/bortezomib lowers the
      percentage of idiotype positive cells and the serum levels of M-protein. Overall
      results define MP0250 as a strong antiangiogenic agent with potential as a novel
      combination drug for treatment of MM patients.

PMID- 29568364
TI  - Efficacy of different spinal nerve roots for neuromodulation of micturition
      reflex in rats.
AB  - Electrical stimulation of peripheral nerves controlling the bladder is an
      alternative, nondestructive medical treatment for urinary incontinence and
      retention. In this study, we aimed to identify the most efficient sensory and
      motor spinal nerve roots involved in the micturition reflex. Unilateral L5-S2
      dorsal and ventral roots were electrically stimulated, and bladder reflex
      contractions were recorded under isovolumetric conditions. Repeated stimulation
      of the L6 and S1 dorsal roots not only abolished bladder reflex contractions but
      also induced a poststimulation inhibitory effect, whereas repeated stimulation of
      the L5 and S2 dorsal roots had no effect. Only the L6 ventral root directly
      caused bladder contraction when ventral roots L5-S2 were stimulated in sequence.
      Upon retrograde tracing using pseudorabies virus (PRV), the sacral
      parasympathetic nucleus of the L6 segment had more PRV-positive cells than the
      other segments, though the S1 segment of the dorsal root ganglia had the highest
      density of PRV-positive neurons. These results suggest the L6 ventral root is
      most efficient in producing detrusor muscle contraction, and the S1 dorsal root
      best inhibits the micturition reflex.

PMID- 29568365
TI  - Amiodarone promotes cancer cell death through elevated truncated SRSF3 and
      downregulation of miR-224.
AB  - Amiodarone is a widely used class III antiarrhythmic agent which prolongs the
      action potential and refractory period by blockage of several types of myocardial
      potassium channels. Emerging evidence suggests that amiodarone sensitize tumor
      cells in response to chemotherapy. Nevertheless, little is known about the
      underlying molecular mechanism. To gain further insight, we demonstrated that
      amiodarone accumulated the population of a premature termination codon-containing
      isoform of serine and arginine rich splicing factor 3 (SRSF3-PTC) without
      increasing alternative spliced p53 beta isoform. Amiodarone enhanced reactive
      oxygen species production and increased cell apoptosis, whereas reduced DNA
      damage. Moreover, amiodarone suppressed miR-224 and increased its target COX-2
      expression. Taken together, our results suggested amiodarone caused cancer cell
      death might be through increased SRSF3-PTC and miR-224 reduction in a p53
      independent manner.

PMID- 29568366
TI  - Selenoprotein K deficiency inhibits melanoma by reducing calcium flux required
      for tumor growth and metastasis.
AB  - Interest has emerged in the therapeutic potential of inhibiting store operated
      calcium (Ca2+) entry (SOCE) for melanoma and other cancers because malignant
      cells exhibit a strong dependence on Ca2+ flux for disease progression. We
      investigated the effects of deleting Selenoprotein K (SELENOK) in melanoma since
      previous work in immune cells showed SELENOK was required for efficient Ca2+ flux
      through the endoplasmic reticulum Ca2+ channel protein, inositol 1,4,5
      trisphosphate receptor (IP3R), which is due to the role SELENOK plays in
      palmitoylating and stabilizing the expression of IP3R. CRISPR/Cas9 was used to
      generate SELENOK-deficiency in human melanoma cells and this led to reduced Ca2+
      flux and impaired IP3R function, which inhibited cell proliferation, invasion,
      and migration. Ca2+-dependent signaling through calcineurin was inhibited with
      SELENOK-deficiency, and gene array analyses together with evaluation of
      transcript and protein levels showed altered transcriptional programs that
      ultimately disrupted stemness and pro-growth properties. In vivo investigations
      were conducted using the Grm1-Tg transgenic mouse strain that develops
      spontaneous metastatic melanoma, which was crossed with SELENOK-/- mice to
      generate the following littermates: Grm1-Tg/SELENOK-/-, Grm1-Tg/SELENOK-/+, Grm1
      Tg/SELENOK+/+. SELENOK-deficiency in Grm1-Tg/SELENOK-/- male and female mice
      inhibited primary tumor growth on tails and ears and reduced metastasis to
      draining lymph nodes down to levels equivalent to non-tumor control mice. Cancer
      stem cell pools were also decreased in Grm1-Tg/SELENOK-/- mice compared to
      littermates. These results suggest that melanoma requires SELENOK expression for
      IP3R dependent maintenance of stemness, tumor growth and metastasic potential,
      thus revealing a new potential therapeutic target for treating melanoma and
      possibly other cancers.

PMID- 29568367
TI  - The new allosteric inhibitor asciminib is susceptible to resistance mediated by
      ABCB1 and ABCG2 overexpression in vitro.
AB  - Asciminib (previously ABL001), which binds the myristate-binding pocket of the
      Bcr-Abl kinase domain, is in phase I clinical trials as monotherapy and in
      combination with imatinib, nilotinib and dasatinib for the treatment of patients
      with refractory CML or Ph+ ALL. Asciminib sensitivity was evaluated in asciminib
      naive BCR-ABL1+ cell lines K562 (negligible ABCB1/ABCG2 expression), K562-Dox
      (ABCB1-overexpressing through doxorubicin exposure) and K562-ABCG2 (ABCG2
      overexpression via transduction) with results demonstrating asciminib efflux by
      both ABCB1 and ABCG2 transporters. K562-Dox and K562-ABCG2 cells demonstrated
      increased LD50asciminib vs K562 control cells: 256 and 299 nM respectively vs 24
      nM, p < 0.001. Sensitivity was completely restored with specific inhibitors
      cyclosporine (ABCB1) and Ko143 (ABCG2): K562-Dox LD50asciminib+cyclosporine = 13
      nM, K562-ABCG2 LD50asciminib+Ko143 = 15 nM (p < 0.001). When asciminib resistance
      was modelled in vitro, ABCB1 and ABCG2 overexpression was integral in the
      development of asciminib resistance. In K562 asciminib-resistant cells, ABCG2
      expression increased prior to BCR-ABL1 overexpression and remained high (up to
      7.6-fold greater levels in resistant vs control cells, p < 0.001). K562-Dox
      asciminib-resistant cells had increased ABCB1 expression (2.1-fold vs control
      cells p = 0.0033). KU812 asciminib-resistant cells overexpressed ABCB1 (5.4-fold
      increase, p < 0.001) and ABCG2 (6-fold increase, p < 0.001) before emergence of a
      novel myristate-binding pocket mutation (F497L). In all three cell lines,
      asciminib resistance was reversible upon chemical inhibition of ABCB1, ABCG2 or
      both (p < 0.001). When K562 asciminib-resistant cells were treated with asciminib
      in combination with clinically achievable doses of either imatinib or nilotinib,
      reversal of the resistance phenotype was also observed (p < 0.01). Overexpression
      of efflux transporters will likely be an important pathway for asciminib
      resistance in the clinical setting. Given the lack of evidence for ABCG2-mediated
      transport of nilotinib or imatinib at clinically relevant concentrations, our
      data provide an additional rationale for using asciminib in combination with
      either TKI.

PMID- 29568368
TI  - Trifluridine/tipiracil overcomes the resistance of human gastric 5-fluorouracil
      refractory cells with high thymidylate synthase expression.
AB  - Trifluridine/tipiracil (FTD/TPI or TFTD, also known as TAS-102) is a combination
      of the antineoplastic thymidine analog, FTD, and thymidine phosphorylase
      inhibitor, TPI (molar ratio 1:0.5). FTD/TPI was approved in Japan, the United
      States, and the European Union for the treatment of unresectable advanced or
      recurrent colorectal cancer. We evaluated the in vitro and in vivo efficacy and
      mechanisms of action of FTD and FTD/TPI against 5-fluorouracil (5-FU)-resistant
      MKN45/5FU, MKN74/5FU, and KATOIII/5FU human gastric cancer cells overexpressing
      thymidylate synthase (TS) and their respective parent cell lines. MKN45/5FU and
      KATOIII/5FU cells were not cross-resistant to FTD, whereas MKN45/5FU cells were
      3.7-fold more resistant than the parental cells in vitro. FTD was also
      incorporated into genomic DNA in a concentration-dependent manner in 5-FU
      resistant and parental cells. Additionally, deoxyuridine monophosphate levels in
      MKN45/5FU cells after 24-h FTD treatment were 3.0-fold higher than those in
      parental cells, and FTD treatment for 72 h induced G2/M arrest in MKN45/5FU
      cells, unlike the S phase arrest in MKN45 cells. Thus, TS-overexpressing
      MKN45/5FU cells, but not MKN74/5FU and KATOIII/5FU cells, showed partial cross
      resistance to FTD. However, FTD/TPI (administered orally twice a day) exhibited
      antitumor activity to the same extent in MKN45 and MKN45/5FU xenograft mouse
      models, overcoming in vitro cross-resistance to FTD. DNA incorporation rather
      than TS inhibition seems to be the main action of FTD under these in vivo
      conditions. Thus, FTD/TPI is a promising chemotherapeutic agent against gastric
      cancers recurring following 5-FU therapy.

PMID- 29568369
TI  - Therapeutic significance of targeting survivin in cervical cancer and possibility
      of combination therapy with TRAIL.
AB  - Loss of p53 function due to human papillomavirus (HPV) infection induces
      resistance to apoptosis in cervical cancer cells. Tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL), which induces apoptosis in a p53-independent
      manner, may provide an alternative strategy for treating cervical cancer.
      Survivin, an antiapoptotic protein that is highly expressed in cancer cells,
      regulates apoptosis and the cell cycle. Here, we investigated the therapeutic
      potential of targeting survivin, while focusing on the TRAIL-induced apoptosis
      pathway. The viability and cell cycle of HPV16-positive CaSki and SiHa cells were
      assessed after survivin knockdown by small interfering RNA (si-survivin). E
      cadherin expression was also assessed after si-survivin treatment, using western
      blotting. SiHa (a TRAIL-resistant cell line) was used for further studies. The
      small molecule YM155 and resveratrol (RVT; a polyphenol with the potential to
      suppress survivin expression) were used as survivin inhibitors. The effects of si
      survivin and survivin inhibitors on TRAIL- or cisplatin (CDDP)-induced apoptosis
      were analyzed by annexin-V staining. si-survivin treatment decreased cell
      viability and led to G2/M arrest, accompanied by morphological changes and E
      cadherin upregulation in both CaSki and SiHa cells. si-survivin and YM155
      synergistically sensitized TRAIL-resistant SiHa cells to TRAIL-induced apoptosis
      (p < 0.05). However, si-survivin and YM155 only slightly increased CDDP-induced
      apoptosis. RVT markedly enhanced TRAIL-induced apoptosis by suppressing survivin
      expression. Targeting of survivin expression might be an ideal strategy for
      cervical cancer treatment as it would decrease viable cell number and enhance
      apoptosis sensitivity. Further, combination therapy with TRAIL, rather than CDDP,
      may be compatible with the proposed survivin-targeting strategy.

PMID- 29568370
TI  - Gram-negative bacteria facilitate tumor progression through TLR4/IL-33 pathway in
      patients with non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) accounts for the most cases in clinical lung
      cancer patients. Patients with NSCLC are often diagnosed in advanced stage and
      frequently infected with gram-negative bacteria. Pulmonary infection with gram
      negative bacteria is the most frequent postoperative complication in NSCLC
      patients. While accumulating evidence indicate an involvement of gram-negative
      bacteria in NSCLC progression, the underlying mechanisms remain largely unknown.
      Herein, we explored the effect of gram-negative bacteria on tumor progression
      using tumor cells from NSCLC patients. We observed that infection with gram
      negative bacteria predicted advanced stages and decreased time interval to
      recurrence of NSCLC patients. Incubation of NSCLC cells with gram-negative
      bacteria promoted their growth and metastasis. Mechanistically, gram-negative
      bacteria activated Toll-like receptor 4 (TLR4) signaling in NSCLC cells, leading
      to increased mRNA and protein expression of interleukin 33 (IL-33) through MyD88
      dependent pathway. Knockdown of IL-33 abrogated the contribution of gram-negative
      bacteria to NSCLC progression by regulating cancer metabolic activities and stem
      cell properties. In NSCLC patients, higher TLR4 expression was associated with
      increased IL-33 expression, Ki-67 proliferation index and CD133 expression in
      those with gram-negative bacterial infection. These findings shed new light on
      the molecular mechanisms underlie gram-negative bacteria mediated tumor
      progression and provide clues for innovative therapeutic explorations for NSCLC
      patients.

PMID- 29568371
TI  - CDK8/19 inhibition induces premature G1/S transition and ATR-dependent cell death
      in prostate cancer cells.
AB  - The CDK8/19 kinase module comprises a subcomplex that interacts with the Mediator
      complex and regulates gene expression through phosphorylation of transcription
      factors and Mediator subunits. Mediator complex subunits have been increasingly
      implicated in cancer and other diseases. Although high expression of CDK8/19 has
      been demonstrated in prostate cancer, its function has not been thoroughly
      examined. Here we report that CDK8/19 modulates the gene expression of cell cycle
      regulators and thereby maintains the proper G1/S transition in prostate cancer
      cells. We show that highly selective CDK8/19 inhibitors exerted anti
      proliferative activity in prostate cancer cells both in vitro and in vivo. In
      CDK8/19 inhibitor-sensitive prostate cancer cells, the compounds reduced the
      population of G1 phase cells and elevated that of S phase cells through the
      modulation of G1/S transition regulators at the level of mRNA expression.
      Furthermore, the premature G1/S transition induced a DNA damage response that was
      followed by ATR-dependent and caspase-independent cell death. These findings
      suggest a novel role of CDK8/19 in transcription-mediated cell cycle control,
      albeit with possible contribution of other proteins inhibited by the compounds.
      Our data provide a rationale for further investigation of CDK8/19 inhibitors as a
      new therapeutic approach to prostate cancer.

PMID- 29568372
TI  - Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head
      and neck squamous cell carcinoma.
AB  - The therapeutic responses of many solid tumours to chemo- and radio-therapies are
      far from fully effective but therapies targeting malignancy-related cellular
      changes show promise for further control. In head and neck squamous cell
      carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed
      and investigation of agents that block this receptor indicate a limited response
      when used alone but an ability to enhance the actions of other drugs. The
      hierarchical stem cell patterns present in tumours generate cellular
      heterogeneity and this is further complicated by cancer stem cells (CSC) shifting
      between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how
      such heterogeneity influences responses to EGFR blocking, we examined the effects
      of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These
      agents reduced cell proliferation for all subpopulations but induced little cell
      death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC
      and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and
      is expected to reduce invasion and metastasis. EGFR blocking also induced shifts
      of Epi-CSCs into the differentiating cell compartment which typically has greater
      sensitivity to chemo/radiation, an effect expected to enhance the overall
      response of tumour cell populations to adjunctive therapies.

PMID- 29568373
TI  - Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor
      prognosis and is associated with triple-negative breast cancer.
AB  - MAP kinase interacting kinases (MNKs) modulate the function of oncogene
      eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is
      necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two
      MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a,
      is constitutively active and independent of upstream MAP kinases. In this study,
      we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples
      and its association with clinicopathologic/prognostic characteristics of breast
      cancer. MNK1a and MNK1b expression was significantly increased in tumors relative
      to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b
      overexpression was found in most of the triple-negative tumors and was associated
      with a shorter overall and disease-free survival time. Overexpression of MNK1b in
      MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic
      protein and promoted proliferation, invasion and colony formation. In conclusion,
      a high expression level of MNK1b protein could be used as a marker of poor
      prognosis in breast cancer patients and it could be a therapeutic target in
      triple-negative tumors.

PMID- 29568374
TI  - An open label trial of folate receptor-targeted intraoperative molecular imaging
      to localize pulmonary squamous cell carcinomas.
AB  - Background: Clinical applicability of folate receptor-targeted intraoperative
      molecular imaging (FR-IMI) has been established for surgically resectable
      pulmonary adenocarcinoma. A role for FR-IMI in other lung cancer histologies has
      not been studied. In this study, we evaluate feasibility of FR-IMI in patients
      undergoing pulmonary resection for squamous cell carcinomas (SCCs). Methods: In a
      human clinical trial (NCT02602119), twelve subjects with pulmonary SCCs underwent
      FR-IMI with a near-infrared contrast agent that targets the folate receptor-alpha
      (FRalpha), OTL38. Near-infrared signal from tumors and benign lung was quantified
      to calculate tumor-to-background ratios (TBR). Folate receptor-alpha expression
      was characterized, and histopathologic correlative analyses were performed to
      evaluate patterns of OTL38 accumulation. An exploratory analysis was performed to
      determine patient and histopathologic variables that predict tumor fluorescence.
      Results: 9 of 13 SCCs (in 9 of 12 of subjects) displayed intraoperative
      fluorescence upon NIR evaluation (median TBR, 3.9). OTL38 accumulated within SCCs
      in a FRalpha-dependent manner. FR-IMI was reliable in localizing nodules as small
      as 1.1 cm, and prevented conversion to thoracotomy for nodule localization in
      three subjects. Upon evaluation of patient and histopathologic variables, in situ
      fluorescence was associated with distance from the pleural surface, and was
      independent of alternative variables including tumor size and metabolic activity.
      Conclusions: This work demonstrates that FR-IMI is potentially feasible in 70% of
      SCC patients, and that molecular imaging can improve localization during
      minimally invasive pulmonary resection. These findings complement previous data
      demonstrating that ~98% of pulmonary adenocarcinomas are localized during FR-IMI
      and suggest broad applicability for NSCLC patients undergoing resection.

PMID- 29568375
TI  - Quantitative mass spectrometry analysis reveals a panel of nine proteins as
      diagnostic markers for colon adenocarcinomas.
AB  - Adenocarcinomas are cancers originating from the gland forming cells of the colon
      and rectal lining, and are known to be the most common type of colorectal
      cancers. The current diagnosis strategies for colorectal cancers include biopsy,
      laboratory tests, and colonoscopy which are time consuming. Identification of
      protein biomarkers could aid in the detection of colon adenocarcinomas (CACs). In
      this study, tissue proteome of colon adenocarcinomas (n = 11) was compared with
      the matched control specimens (n = 11) using isobaric tags for relative and
      absolute quantitation (iTRAQ) based liquid chromatography-mass spectrometry (LC
      MS/MS) approach. A list of 285 significantly altered proteins was identified in
      colon adenocarcinomas as compared to its matched controls, which are associated
      with growth and malignancy of the tumors. Protein interaction analysis revealed
      the association of altered proteins in colon adenocarcinomas with various
      transcription factors and their targets. A panel of nine proteins was validated
      using multiple reaction monitoring (MRM). Additionally, S100A9 was also validated
      using immunoblotting. The identified panel of proteins may serve as potential
      biomarkers and thereby aid in the detection of colon adenocarcinomas.

PMID- 29568376
TI  - CHL1 gene polymorphisms increase lung cancer susceptibility.
AB  - Lung cancer represents a complex and malignant cancer. Close Homologue of L1
      (CHL1) gene plays a crucial role in the progress of cancer. The aim of this study
      is to explore the association between CHL1 rs425366 polymorphism and lung cancer
      susceptibility in northeast of China. A hospital-based case-control study was
      carried out to collect relative characteristics. Logistic regression analysis was
      conducted to analyze the relationship between single nucleotide polymorphisms and
      lung cancer susceptibility. The results suggested that there was statistically
      significant difference between GT genotype and TT genotype of rs425366 and lung
      cancer susceptibility. In stratified analysis, TT genotype of rs425366 may
      increase the risk of lung adenocarcinoma. We also found that non-smoking
      individuals carrying T allele were more likely to develop lung cancer. Overall,
      our study may indicate that CHL1 gene may increase lung cancer susceptibility in
      northeast of China.

PMID- 29568377
TI  - Molecular profiling of ALDH1+ colorectal cancer stem cells reveals preferential
      activation of MAPK, FAK, and oxidative stress pro-survival signalling pathways.
AB  - Tumour heterogeneity leads to variable clinical response and inaccurate
      diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a
      subpopulation responsible for invasion, metastasis, therapeutic resistance, and
      recurrence in many human cancer types. However, the true identity of colorectal
      cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the
      gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH+
      positive cells are clonogenic and highly proliferative; their global gene
      expression profiling-based molecular signature revealed gene enrichment related
      to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH+
      cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway
      pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil
      increased the ALDH+ cell fraction among the SW403, HCT116 and SW620 CRC models.
      Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or
      420 patients for overall (OS) or disease-free (DFS) survival, respectively,
      obtained from the Cancer Genome Atlas CRC dataset, revealed strong association
      between elevated expression and poor OS (p = 0.006) and poor DFS (p = 0.05), thus
      implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct
      molecular signature of ALDH+ CSCs in CRC and suggest pathways relevant for
      successful targeted therapies and management of CRC.

PMID- 29568378
TI  - Human tripartite motif protein 52 is required for cell context-dependent
      proliferation.
AB  - Tripartite motif (TRIM) proteins have been shown to play important roles in
      cancer development and progression by modulating cell proliferation or resistance
      from cell death during non-homeostatic stress conditions found in tumor micro
      environments. In this study, we set out to investigate the importance for
      cellular fitness of the virtually uncharacterized family member TRIM52. The human
      TRIM52 gene has arisen recently in evolution, making it unlikely that TRIM52 is
      required for basic cellular functions in normal cells. However, a recent genome
      wide ablation screening study has suggested that TRIM52 may be essential for
      optimal proliferation or survival in certain genetic cancer backgrounds.
      Identifying genes which fit this concept of genetic context-dependent fitness in
      cancer cells is of interest as they are promising targets for tumor-specific
      therapy. We report here that TRIM52 ablation significantly diminished the
      proliferation of specific glioblastoma cell lines in cell culture and mouse
      xenografts by compromising their cell cycle progression in a p53-dependent
      manner. Together, our findings point to a non-redundant TRIM52 function that is
      required for optimal proliferation.

PMID- 29568379
TI  - Leukocyte telomere length throughout the continuum of colorectal carcinogenesis.
AB  - Considering the high prevalence of colorectal cancer (CRC) and relatively high
      mortality there is strong interest in identification of clinically relevant
      biomarkers. Telomere shortening is supposed to contribute to genomic instability
      and crucially involved in process of carcinogenesis. Peripheral blood leukocyte
      (PBL) telomere length was previously investigated in several studies as potential
      biomarker for CRC but with controversial results. This prompted us to investigate
      relative PBL telomere length in association with different histological findings
      throughout the continuum of colorectal carcinogenesis in order to reflect the
      whole spectrum of putative CRC development in a large study involving 2011
      individuals. The study based on the Colorectal Cancer Study of Austria (CORSA),
      including 384 CRC cases as well as age- and gender-matched 544 high-risk
      adenomas, 537 low-risk adenoma patients and 546 colonoscopy-negative controls.
      Relative expression of telomeric repeats and the single copy reference gene,
      albumin (T/S ratio) was determined using monochrome multiplex quantitative PCR
      (MMQPCR). Telomeres were found to be significantly longer in CRC patients
      compared to control subjects (P = 3.61x10-6). Yet, no significant differences in
      telomere length could be detected for high-risk (P = 0.05956) and low-risk
      colorectal adenoma patients (P = 0.05224). In addition, results presented in this
      manuscript highlight the impact of various epidemiological factors on PBL
      telomere length and its involvement in CRC. However, further large studies also
      including colorectal adenomas are necessary to confirm these results.

PMID- 29568380
TI  - Adenosine A2A receptor ligand recognition and signaling is blocked by A2B
      receptors.
AB  - The adenosine receptor (AR) subtypes A2A and A2B are rhodopsin-like Gs protein
      coupled receptors whose expression is highly regulated under pathological, e.g.
      hypoxic, ischemic and inflammatory conditions. Both receptors play important
      roles in inflammatory and neurodegenerative diseases, are blocked by caffeine,
      and have now become major drug targets in immuno-oncology. By Forster resonance
      energy transfer (FRET), bioluminescence resonance energy transfer (BRET),
      bimolecular fluorescence complementation (BiFC) and proximity ligation assays
      (PLA) we demonstrated A2A-A2BAR heteromeric complex formation. Moreover we
      observed a dramatically altered pharmacology of the A2AAR when co-expressed with
      the A2BAR (A2B >= A2A) in recombinant as well as in native cells. In the presence
      of A2BARs, A2A-selective ligands lost high affinity binding to A2AARs and
      displayed strongly reduced potency in cAMP accumulation and dynamic mass
      redistribution (DMR) assays. These results have major implications for the use of
      A2AAR ligands as drugs as they will fail to modulate the receptor in an A2A-A2B
      heteromer context. Accordingly, A2A-A2BAR heteromers represent novel
      pharmacological targets.

PMID- 29568381
TI  - Nuclear myosin/actin-motored contact between homologous chromosomes is initiated
      by ATM kinase and homology-directed repair proteins at double-strand DNA breaks
      to suppress chromosome rearrangements.
AB  - We provide evidence for a mechanism of DNA repair that requires nuclear
      myosin/actin-dependent contact between homologous chromosomes to prevent
      formation of chromosomal rearrangement in human cells. We recently showed that
      DNA double strand breaks (DSBs) induced by gamma-rays or endonucleases cause ATM
      dependent contact formation between homologous chromosomes at damaged sites of
      transcriptionally active chromatin in G0/G1-phase cells. Here, we report that the
      mechanism of contact generation between homologous chromosomes also requires
      homology-directed repair proteins, including BRCA1, RAD51 and RAD52, and nuclear
      myosin/actin-motors. Moreover, inhibition of ATM kinase or deficiency in nuclear
      actin polymerization causes carcinogenic RET/PTC chromosome rearrangements after
      DSBs induction in human cells. These data suggest that DSBs in transcriptionally
      active euchromatin in G0/G1-phase cells are repaired through a mechanism that
      requires contact formation between homologous chromosomes and that this mechanism
      is mediated by HDR proteins and nuclear myosin/actin motors.

PMID- 29568382
TI  - Prolonged in vivo expression and anti-tumor response of DNA-based anti-HER2
      antibodies.
AB  - Antibody gene transfer presents an appealing alternative to conventional antibody
      protein therapy. This pre-clinical study evaluates the impact of various
      parameters on the pharmacokinetics and efficacy of in vivo expressed DNA-based
      anti-HER2 monoclonal antibodies (mAbs), newly engineered and delivered via
      intramuscular electrotransfer in mice. Plasma concentrations of trastuzumab and
      4D5, its murine IgG1 equivalent, peaked on average between 1-15 ug/ml, depending
      on the administration and configuration of the encoding plasmid DNA (pDNA). A
      dual expression cassette system outperformed a single 2A-based cassette, and the
      CAG promoter was superior to a muscle-specific DeltaUSE-based promoter. A 'gene
      therapy-compatible' Gene Transport Unit (gtGTU, FIT Biotech), a plasmid backbone
      that co-encodes viral elements, failed to improve in vivo reporter and mAb
      expression compared to a conventional plasmid. In BALB/c mice, trastuzumab
      detection was lost within two weeks after pDNA administration due to anti-drug
      antibodies. This host immune response was addressed by expressing trastuzumab in
      immune-compromised mice, or by gene transfer of murine 4D5 in BALB/c mice. Both
      approaches maintained single-digit ug/ml mAb concentrations for at least six to
      nine months, and allowed to boost mAb expression over time by pDNA re-dosing. In
      a breast cancer mouse model, prophylactic and therapeutic DNA-based trastuzumab
      or 4D5 led to complete tumor regressions, thereby rivalling with the
      administration of milligrams of mAb protein. In conclusion, our study
      demonstrates proof of concept for antibody gene transfer in cancer, provides
      critical insights in the engineering and application of DNA-based antibodies, and
      serves to advance this modality in oncology and beyond.

PMID- 29568383
TI  - Protective role of integrin-linked kinase against oxidative stress and in
      maintenance of genomic integrity.
AB  - The balance between the production of reactive oxygen species and activation of
      antioxidant pathways is essential to maintain a normal redox state in all
      tissues. Oxidative stress caused by excessive oxidant species generation can
      cause damage to DNA and other macromolecules, affecting cell function and
      viability. Here we show that integrin-linked kinase (ILK) plays a key role in
      eliciting a protective response to oxidative damage in epidermal cells.
      Inactivation of the Ilk gene causes elevated levels of intracellular oxidant
      species (IOS) and DNA damage in the absence of exogenous oxidative insults. In
      ILK-deficient cells, excessive IOS production can be prevented through inhibition
      of NADPH oxidase activity, with a concomitant reduction in DNA damage.
      Additionally, ILK is necessary for DNA repair processes following UVB-induced
      damage, as ILK-deficient cells show a significantly impaired ability to remove
      cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to
      maintain cellular redox balance and, in its absence, epidermal cells become more
      susceptible to oxidative damage through mechanisms that involve IOS production by
      NADPH oxidase activity.

PMID- 29568384
TI  - Structural insights into drug development strategy targeting EGFR T790M/C797S.
AB  - Treatment of non-small-cell lung cancers (NSCLCs) harboring primary EGFR
      oncogenic mutations such as L858R and exon 19 deletion delE746_A750 (Del-19)
      using gefitinib/erlotinib ultimately fails due to the emergence of T790M
      mutation. Though WZ4002/CO-1686/AZD9291 are effective in overcoming EGFR T790M by
      targeting Cys797 via covalent bonding, their efficacy is again limited due to the
      emergence of C797S mutation. New agents effectively inhibiting EGFR T790M without
      covalent linkage through Cys 797 may solve this problem. We presented here
      crystal structures of EGFR activating/drug-resistant mutants in complex with a
      panel of reversible inhibitors along with mutagenesis and enzyme kinetic data.
      These data revealed a previously un-described hydrophobic clamp structure in the
      EGFR kinase which may be exploited to facilitate development of next generation
      drugs targeting EGFR T790M with or without concomitant C797S. Interestingly,
      mutations in the hydrophobic clamp that hinder drug binding often also weaken ATP
      binding and/or abolish kinase activity, thus do not readily result in resistance
      to the drugs.

PMID- 29568385
TI  - Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts.
AB  - Cancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as
      they promote tumour growth and metastatic potential. However, CAF targeting is
      complicated by the lack of knowledge-based strategies aiming to selectively
      eliminate these cells. There is a growing body of evidence suggesting that a pro
      inflammatory microenvironment (e.g. ROS and cytokines) promotes CAF formation
      during tumorigenesis, although the exact mechanisms involved remain unclear. In
      this study, we reveal that a prolonged pro-inflammatory stimulation causes a de
      facto deficiency in base excision repair, generating unrepaired DNA strand breaks
      and thereby triggering an ATF4-dependent reprogramming of normal fibroblasts into
      CAF-like cells. Based on the phenotype of in vitro-generated CAFs, we demonstrate
      that midostaurin, a clinically relevant compound, selectively eliminates CAF-like
      cells deficient in base excision repair and prevents their stimulatory role in
      cancer cell growth and migration.

PMID- 29568386
TI  - Correlation of MET gene amplification and TP53 mutation with PD-L1 expression in
      non-small cell lung cancer.
AB  - Background: The role of MET amplification in lung cancer, particularly in
      relation to checkpoint inhibition and EGFR WT, has not been fully explored. In
      this study, we correlated PD-L1 expression with MET amplification and EGFR, KRAS,
      or TP53 mutation in primary lung cancer. Methods: In this retrospective study,
      tissue collected from 471 various tumors, including 397 lung cancers, was tested
      for MET amplification by FISH with a MET/centromere probe. PD-L1 expression was
      evaluated using clone SP142 and standard immunohistochemistry, and TP53, KRAS,
      and EGFR mutations were tested using next generation sequencing. Results: Our
      results revealed that PD-L1 expression in non-small cell lung cancer is inversely
      correlated with EGFR mutation (P=0.0003), and positively correlated with TP53
      mutation (P=0.0001) and MET amplification (P=0.004). Patients with TP53 mutations
      had significantly higher MET amplification (P=0.007), and were more likely
      (P=0.0002) to be EGFR wild type. There was no correlation between KRAS mutation
      and overall PD-L1 expression, but significant positive correlation between PD-L1
      expression and KRAS with TP53 co-mutation (P=0.0002). A cut-off for the ratio of
      MET: centromere signal was determined as 1.5%, and 4% of lung cancer patients
      were identified as MET amplified. Conclusions: This data suggests that in lung
      cancer both MET and TP53 play direct roles in regulating PD-L1 opposing EGFR.
      Moreover, KRAS and TP53 co-mutation may cooperate to drive PD-L1 expression in
      lung cancer. Adding MET or TP53 inhibitors to checkpoint inhibitors may be an
      attractive combination therapy in patients with lung cancer and MET
      amplification.

PMID- 29568387
TI  - Engineered T lymphocytes eliminate lung metastases in models of pancreatic
      cancer.
AB  - Pancreatic cancer is known as one of the most lethal cancers in the world. A
      majority of advanced stage pancreatic cancer patients are diagnosed with distant
      metastasis and given poor prognoses, calling for a better therapeutic option.
      Mesothelin, which is overexpressed in pancreatic cancer and other solid tumors,
      is a potential target for pancreatic cancer immunotherapy. Adoptive transfer of T
      cells engineered with chimeric antigen receptors (CART cells) was effective for
      treating CD19-positive leukemia, but it is more difficult for CART cells to
      eliminate solid tumors. Because distal metastasis is an important malignant
      behavior of solid tumors, we investigated whether meso-CART cells exert anti
      tumor effects against distant metastases. After expressing meso-CAR in human
      primary T lymphocytes, the resultant meso-CART cells released cytokines in
      response to and exhibited cytolytic effects on mesothelin-positive tumor cells in
      vitro. Injection of meso-CART cells into tumor-bearing mice moderately delayed
      subcutaneous tumor growth and eliminated lung metastases. This is the first study
      to show that meso-CART cells are effective against lung metastases induced by
      intravenous injection of pancreatic tumor cells. Our results suggest that meso
      CART cells may be an effective clinical treatment for mesothelin-positive primary
      and metastatic tumors in pancreatic cancer patients.

PMID- 29568388
TI  - Inter-assay precision of clonogenic assays for radiosensitivity in cancer cell
      line A549.
AB  - Clonogenic assays are the gold standard for determining radiosensitivity, which
      governs tumor response to radiation therapy. Although multiple studies of
      clonogenic assays on cancer cell lines have been published, the robustness of
      this technique has not been examined by comparative analysis of data from
      different studies. To address this issue, we investigated the inter-assay
      precision of clonogenic assays by analyzing in-house and published data on A549,
      a cell line frequently studied in this context. The coefficients of variation for
      SF2, the surviving fraction after 2 Gy irradiation, and D10, the radiation dose
      that reduces survival to 10%, were below 30% for both in-house data obtained from
      20 independent experiments performed under consistent experimental settings
      (i.e., radiation type, dose rate, and timing of cell seeding) and data collected
      from 192 publications using diverse experimental settings. Multivariate analyses
      of the published data revealed that timing of cell seeding significantly affected
      SF2. These data indicate that SF2 and D10 of clonogenic assay have acceptable
      inter-assay precision, and that timing of cell seeding influences the inter-assay
      precision of SF2. These results provide a rationale for combined analysis of
      published clonogenic assay data, which may help to discover robust biological
      properties associated with tumor radiosensitivity.

PMID- 29568389
TI  - Computational modeling suggests impaired interactions between NKX2.5 and GATA4 in
      individuals carrying a novel pathogenic D16N NKX2.5 mutation.
AB  - NKX2.5, a homeobox containing gene, plays an important role in embryonic heart
      development and associated mutations are linked with various cardiac
      abnormalities. We sequenced the NKX2.5 gene in 100 congenital heart disease (CHD)
      patients and 200 controls. Our analysis revealed a total of 7 mutations, 3 in
      intronic region, 3 in coding region and 1 in 3' UTR. Of the above mutations, one
      mutation was found to be associated with tetralogy of fallot (TOF) and two
      (rs2277923 and a novel mutation, D16N) were strongly associated with VSD. A novel
      missense mutation, D16N (p-value =0.009744), located in the tinman (TN) region
      and associated with ventricular septal defect (VSD), is the most significant
      findings of this study. Computational analysis revealed that D16N mutation is
      pathogenic in nature. Through the molecular modeling, docking and molecular
      dynamics simulation studies, we have identified the location of mutant D16N in
      NKX2.5 and its interaction map with other partners at the atomic level. We found
      NKX2.5-GATA4 complex is stable, however, in case of mutant we observed
      significant conformational changes and loss of key polar interactions, which
      might be a cause of the pathogenic behavior. This study underscores the
      structural basis of D16N pathogenic mutation in the regulation of NKX2.5 and how
      this mutation renders the structural-functional divergence that possibly leading
      towards the diseased state.

PMID- 29568390
TI  - Characterization of brain tumor initiating cells isolated from an animal model of
      CNS primitive neuroectodermal tumors.
AB  - CNS Primitive Neuroectodermal tumors (CNS-PNETs) are members of the embryonal
      family of malignant childhood brain tumors, which remain refractory to current
      therapeutic treatments. Current paradigm of brain tumorigenesis implicates brain
      tumor-initiating cells (BTIC) in the onset of tumorigenesis and tumor
      maintenance. However, despite their significance, there is currently no
      comprehensive characterization of CNS-PNETs BTICs. Recently, we described an
      animal model of CNS-PNET generated by orthotopic transplantation of human Radial
      Glial (RG) cells - the progenitor cells for adult neural stem cells (NSC) - into
      NOD-SCID mice brain and proposed that BTICs may play a role in the maintenance of
      these tumors. Here we report the characterization of BTIC lines derived from this
      CNS-PNET animal model. BTIC's orthotopic transplantation generated highly
      aggressive tumors also characterized as CNS-PNETs. The BTICs have the hallmarks
      of NSCs as they demonstrate self-renewing capacity and have the ability to
      differentiate into astrocytes and early migrating neurons. Moreover, the cells
      demonstrate aberrant accumulation of wild type tumor-suppressor protein p53,
      indicating its functional inactivation, highly up-regulated levels of onco
      protein cMYC and the BTIC marker OCT3/4, along with metabolic switch to
      glycolysis - suggesting that these changes occurred in the early stages of
      tumorigenesis. Furthermore, based on RNA- and DNA-seq data, the BTICs did not
      acquire any transcriptome-changing genomic alterations indicating that the onset
      of tumorigenesis may be epigenetically driven. The study of these BTIC self
      renewing cells in our model may enable uncovering the molecular alterations that
      are responsible for the onset and maintenance of the malignant PNET phenotype.

PMID- 29568391
TI  - Proline oxidase silencing induces proline-dependent pro-survival pathways in MCF
      7 cells.
AB  - Proline degradation by proline dehydrogenase/proline oxidase (PRODH/POX)
      contributes to apoptosis or autophagy. The identification of specific pathway of
      apoptosis/survival regulation is the aim of this study. We generated knocked-down
      PRODH/POX MCF-7 breast cancer cells (MCF-7shPRODH/POX). PRODH/POX silencing did
      not affect cell viability. However, it contributed to decrease in DNA and
      collagen biosynthesis, increase in prolidase activity and intracellular proline
      concentration as well as increase in the expression of iNOS, NF-kappaB, mTOR, HIF
      1alpha, COX-2, AMPK, Atg7 and Beclin-1 in MCF-7shPRODH/POX cells. In these cells,
      glycyl-proline (GlyPro, substrate for prolidase) further inhibited DNA and
      collagen biosynthesis, maintained high prolidase activity, intracellular
      concentration of proline and up-regulated HIF-1alpha, AMPK, Atg7 and Beclin-1,
      compared to GlyPro-treated MCF-7 cells. In MCF-7 cells, GlyPro increased collagen
      biosynthesis, concentration of proline and expression of caspase-3, cleaved
      caspases -3 and -9, iNOS, NF-kappaB, COX-2 and AMPKbeta. PRODH/POX knock-down
      contributed to pro-survival autophagy pathways in MCF-7 cells and GlyPro-derived
      proline augmented this process. However, GlyPro induced apoptosis in PRODH/POX
      expressing MCF-7 cells as detected by up-regulation of active caspases -3 and -9.
      The data suggest that PRODH/POX silencing induces autophagy in MCF-7 cells and
      GlyPro-derived proline supports this process.

PMID- 29568392
TI  - MicroRNA-630 may confer favorable cisplatin-based chemotherapy and clinical
      outcomes in non-small cell lung cancer by targeting Bcl-2.
AB  - MicroRNA-630 (miR-630) plays dual roles in tumor progression in various human
      cancers. However, the role of miR-630 in chemoresistance and prognosis in non
      small cell lung cancer (NSCLC) remains to be elucidated. This retrospective study
      enrolled 114 surgically resected patients with NSCLC who experienced tumor
      relapse and underwent cisplatin-based chemotherapy. The aim was to examine the
      possible association between miR-630 (and its targeting of Bcl-2 expression) and
      the response to cisplatin-based chemotherapy. Patients with tumors expressing low
      miR-630, high Bcl-2, and a combination of both were more likely than their
      counterparts to show unfavorable responses to cisplatin-based chemotherapy.
      Kaplan-Meier and Cox regression analysis indicated that low miR-630, high Bcl-2,
      and a combination of both may independently predict poor overall survival and
      short relapse-free survival in patients with NSCLC. Six types of NSCLC cells were
      collected to determine the inhibitory concentration of cisplatin yielding 50%
      viability (IC50) by the MTT assay. The IC50 value for cisplatin was negatively
      correlated with miR-630 expression levels among these cell types, except for A549
      cells. Mechanistically, low miR-630 expression conferred cisplatin resistance and
      colony formation by de-targeting Bcl-2 in NSCLC cells. We therefore suggest that
      low miR-630, high Bcl-2, and a combination of both may potentially predict an
      unfavorable chemotherapeutic response and poor outcome in patients with NSCLC.

PMID- 29568393
TI  - Artificial neural network approach to predict surgical site infection after free
      flap reconstruction in patients receiving surgery for head and neck cancer.
AB  - Background: The aim of this study was to develop an effective surgical site
      infection (SSI) prediction model in patients receiving free-flap reconstruction
      after surgery for head and neck cancer using artificial neural network (ANN), and
      to compare its predictive power with that of conventional logistic regression
      (LR). Materials and methods: There were 1,836 patients with 1,854 free-flap
      reconstructions and 438 postoperative SSIs in the dataset for analysis. They were
      randomly assigned tin ratio of 7:3 into a training set and a test set. Based on
      comprehensive characteristics of patients and diseases in the absence or presence
      of operative data, prediction of SSI was performed at two time points (pre
      operatively and post-operatively) with a feed-forward ANN and the LR models. In
      addition to the calculated accuracy, sensitivity, and specificity, the predictive
      performance of ANN and LR were assessed based on area under the curve (AUC)
      measures of receiver operator characteristic curves and Brier score. Results: ANN
      had a significantly higher AUC (0.892) of post-operative prediction and AUC
      (0.808) of pre-operative prediction than LR (both P<0.0001). In addition, there
      was significant higher AUC of post-operative prediction than pre-operative
      prediction by ANN (p<0.0001). With the highest AUC and the lowest Brier score
      (0.090), the post-operative prediction by ANN had the highest overall predictive
      performance. Conclusion: The post-operative prediction by ANN had the highest
      overall performance in predicting SSI after free-flap reconstruction in patients
      receiving surgery for head and neck cancer.

PMID- 29568394
TI  - Cardiac glycoside bufalin blocks cancer cell growth by inhibition of Aurora A and
      Aurora B activation via PI3K-Akt pathway.
AB  - In our previous study, cardiac glycosides including bufalin, a group of sodium
      pump (Na+/K+-ATPase) inhibitors widely used to treat heart failure for many
      years, have been demonstrated to induce a delay of mitotic entry and mitotic
      arrest in many cancer cells. However, the underlying mechanism remains poorly
      understood. Here, we reported for the first time that cardiac glycoside bufalin
      induced mitotic entry delay and prometaphase arrest by inhibition of activation
      of Aurora A/B. Furthermore, cardiac glycoside bufalin prevented Aurora A
      recruitment to mitotic centrosomes and Aurora B recruitment to unattached
      kinetochores. Mechanistically, bufalin and knockdown of sodium pump inhibited
      PI3K-Akt pathway, which in turn inhibit the activation of Aurora A/B, followed by
      a delay in mitotic entry and mitotic arrest. These actions were reversed by
      overexpression of Akt. In addition, ERK, mTOR, and ROS are not involved in
      bufalin-mediated downregulation of active form of Aurora A/B. Taken together,
      cardiac glycoside bufalin induces mitotic entry delay and mitotic arrest in
      cancer cells through inhibition of Aurora A/B activation via PI3K-Akt pathway.
      Based on this novel finding we could suggest that targeting PI3K-Akt pathway may
      have therapeutic value for the treatment of cancers associated with sodium pump
      overexpression.

PMID- 29568395
TI  - Merestinib (LY2801653) inhibits neurotrophic receptor kinase (NTRK) and
      suppresses growth of NTRK fusion bearing tumors.
AB  - Merestinib is an oral multi-kinase inhibitor targeting a limited number of
      oncokinases including MET, AXL, RON and MKNK1/2. Here, we report that merestinib
      inhibits neurotrophic receptor tyrosine kinases NTRK1/2/3 which are oncogenic
      drivers in tumors bearing NTRK fusion resulting from chromosomal rearrangements.
      Merestinib is shown to be a type II NTRK1 kinase inhibitor as determined by x-ray
      crystallography. In KM-12 cells harboring TPM3-NTRK1 fusion, merestinib exhibits
      potent p-NTRK1 inhibition in vitro by western blot and elicits an anti
      proliferative response in two- and three-dimensional growth. Merestinib treatment
      demonstrated profound tumor growth inhibition in in vivo cancer models harboring
      either a TPM3-NTRK1 or an ETV6-NTRK3 gene fusion. To recapitulate resistance
      observed from type I NTRK kinase inhibitors entrectinib and larotrectinib, we
      generated NIH-3T3 cells exogenously expressing TPM3-NTRK1 wild-type, or acquired
      mutations G595R and G667C in vitro and in vivo. Merestinib blocks tumor growth of
      both wild-type and mutant G667C TPM3-NTRK1 expressing NIH-3T3 cell-derived
      tumors. These preclinical data support the clinical evaluation of merestinib, a
      type II NTRK kinase inhibitor (NCT02920996), both in treatment naive patients and
      in patients progressed on type I NTRK kinase inhibitors with acquired secondary
      G667C mutation in NTRK fusion bearing tumors.

PMID- 29568396
TI  - Integrated DNA methylation analysis identifies topographical and tumoral
      biomarkers in pilocytic astrocytomas.
AB  - Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and
      occurs in different locations. Chromosomal alterations are mostly located at
      chromosome 7q34 comprising the BRAF oncogene with consequent activation of the
      mitogen-activated protein kinase pathway. Although genetic and epigenetic
      alterations characterizing PA from different localizations have been reported,
      the role of epigenetic alterations in PA development is still not clear. The aim
      of this study was to investigate whether distinctive methylation patterns may
      define biologically relevant groups of PAs. Integrated DNA methylation analysis
      was performed on 20 PAs and 4 normal brain samples by Illumina Infinium
      HumanMethylation27 BeadChips. We identified distinct methylation profiles
      characterizing PAs from different locations (infratentorial vs supratentorial)
      and tumors with onset before and after 3 years of age. These results suggest that
      PA may be related to the specific brain site where the tumor arises from region
      specific cells of origin. We identified and validated in silico the methylation
      alterations of some CpG islands. Furthermore, we evaluated the expression levels
      of selected differentially methylated genes and identified two biomarkers, one,
      IRX2, related to the tumor localization and the other, TOX2, as tumoral
      biomarker.

PMID- 29568397
TI  - Nucleolar stress enhances lytic reactivation of the Kaposi's sarcoma-associated
      herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumorigenic virus
      exhibiting two forms of infection, latent and lytic. Latent infection is abortive
      and allows the virus to establish lifelong infection, while lytic infection is
      productive, and is needed for virus dissemination within the host and between
      hosts. Latent infection may reactivate and switch towards the lytic cycle. This
      switch is a critical step in the maintenance of long-term infection and for the
      development of KSHV-related neoplasms. In this study, we examined the effect of
      nucleolar stress, manifested by failure in ribosome biogenesis or function and
      often coupled with p53 activation, on lytic reactivation of KSHV. To this end, we
      induced nucleolar stress by treatment with Actinomycin D, CX-5461 or BMH-21.
      Treatment with these compounds alone did not induce the lytic cycle. However,
      enhancement of the lytic cycle by these compounds was evident when combined with
      expression of the viral protein K-Rta. Further experiments employing combined
      treatments with Nutlin-3, knock-down of p53 and isogenic p53+/+ and p53-/- cells
      indicated that the enhancement of lytic reactivation by nucleolar stress does not
      depend on p53. Thus, our study identifies nucleolar stress as a novel regulator
      of KSHV infection, which synergizes with K-Rta expression to increase lytic
      reactivation. This suggests that certain therapeutic interventions, which induce
      nucleolar stress, may affect the outcome of KSHV infection.

PMID- 29568398
TI  - Bcl-xL as a poor prognostic biomarker and predictor of response to adjuvant
      chemotherapy specifically in BRAF-mutant stage II and III colon cancer.
AB  - Purpose: BRAF mutation occurs in 8-15% of colon cancers (CC), and is associated
      with poor prognosis in metastatic disease. Compared to wild-type BRAF (BRAFWT)
      disease, stage II/III CC patients with BRAF mutant (BRAFMT) tumors have shorter
      overall survival after relapse; however, time-to-relapse is not significantly
      different. The aim of this investigation was to identify, and validate, novel
      predictors of relapse of stage II/III BRAFMT CC. Experimental design: We used
      gene expression data from a cohort of 460 patients (GSE39582) to perform a
      supervised classification analysis based on risk-of-relapse within BRAFMT stage
      II/III CC, to identify transcriptomic biomarkers associated with prognosis within
      this genotype. These findings were validated using immunohistochemistry in an
      independent population-based cohort of Stage II/III CC (n = 691), applying Cox
      proportional hazards analysis to determine associations with survival. Results:
      High gene expression levels of Bcl-xL, a key regulator of apoptosis, were
      associated with increased risk of relapse, specifically in BRAFMT tumors (HR =
      8.3, 95% CI 1.7-41.7), but not KRASMT/BRAFWT or KRASWT/BRAFWT tumors. High Bcl-xL
      protein expression in BRAFMT, untreated, stage II/III CC was confirmed to be
      associated with an increased risk of death in an independent cohort (HR = 12.13,
      95% CI 2.49-59.13). Additionally, BRAFMT tumors with high levels of Bcl-xL
      protein expression appeared to benefit from adjuvant chemotherapy (P for
      interaction = 0.006), indicating the potential predictive value of Bcl-xL
      expression in this setting. Conclusions: These findings provide evidence that Bcl
      xL gene and/or protein expression identifies a poor prognostic subgroup of BRAFMT
      stage II/III CC patients, who may benefit from adjuvant chemotherapy.

PMID- 29568399
TI  - CTBP1 and metabolic syndrome induce an mRNA and miRNA expression profile critical
      for breast cancer progression and metastasis.
AB  - Metastatic breast cancer (BrCa) is still one of the main causes of cancer death
      in women. Metabolic syndrome (MeS), a risk factor for BrCa, is associated to high
      grade tumors, increased metastasis and recurrence of this disease. C-terminal
      binding protein 1 (CTBP1) is a co-repressor of tumor suppressor genes that is
      activated by low NAD+/NADH ratio. Previously, we demonstrated that CTBP1
      hyperactivation by MeS increased tumor growth in MDA-MB-231-derived xenografts
      regulating several genes and miRNAs. In this work, our aim was to elucidate the
      role of CTBP1 and MeS in BrCa metastasis. We found that CTBP1 protein diminished
      adhesion while increased migration of triple negative BrCa cells. CTBP1 and MeS
      modulated the expression of multiple genes (ITGB4, ITGB6, PRSS2, COL17A1 and
      FABP4) and miRNAs (miR-378a-3p, miR-146a-5p, let-7e-3p, miR-381-5p, miR-194-5p,
      miR-494-3p) involved in BrCa progression of MDA-MB-231-derived xenografts.
      Furthermore, we demonstrated that MeS increased lung micrometastasis and liver
      neoplastic disease in mice. CTBP1 hyperactivation seems to be critical for MeS
      effect on BrCa metastasis since CTBP1 depletion completely impaired the detection
      of circulating tumor cells. Our results highlight CTBP1 and MeS impact on BrCa
      progression positioning them as key properties to be considered for BrCa patient
      prognosis and management.

PMID- 29568400
TI  - Chemopreventive effects of angiotensin II receptor type 2 agonist on prostate
      carcinogenesis by the down-regulation of the androgen receptor.
AB  - We recently reported that angiotensin II receptor blockers (ARBs) have
      chemopreventive and chemotherapeutic potential against prostate cancer via the
      reduction of androgen receptor (AR) expression. In this study, we investigated
      the effects of the angiotensin II receptor type 2 (AT2R) agonist Compound 21
      (C21), which is expected to play similar roles to an ARB, on prostate
      carcinogenesis using the transgenic rat for adenocarcinoma of prostate (TRAP)
      model previously established in our laboratory. In vitro analyses of the cell
      growth, Western blotting and reporter gene assays were performed using LNCaP
      cells. TRAP rats at 6 weeks of age were randomly divided into 3 groups of 12
      animals each and treated with C21 at 1 or 2 mg/kg/day in drinking water for 12
      weeks. C21 reduced the proliferation activity of prostate cancer cells and down
      regulated the PSA promoter activity and the AR protein expression. We discovered
      that C21 inhibited the progression of prostate carcinogenesis in TRAP rats and
      decreased the incidence of adenocarcinoma in the lateral prostate. A significant
      increase in the apoptotic index with activation of caspase 3 and 7 were observed
      by immunohistochemistry and Western blotting analyses. C21 also down-regulated
      the expression of AR significantly in TRAP rat prostate. C21 decreased the
      expression of AR and reduced the proliferation activity effectively in prostate
      cancer cells and TRAP rat prostate. These findings suggest that AT2R agonist may
      be a candidate novel chemopreventive agent against human prostate cancer.

PMID- 29568401
TI  - A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in
      tumor and plasma from patients with gastrointestinal stromal tumors.
AB  - Background: Gastrointestinal stromal tumors (GISTs) are characterized by
      oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this
      study was to develop a single, sensitive, quantitative digital droplet PCR
      (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor
      tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients' plasma.
      Methods: A ddPCR assay was designed using two probes that cover both hotspots.
      Available archival FFPE tumor tissue from 27 consecutive patients with known KIT
      exon 11 mutations and 9 randomly selected patients without exon 11 mutations were
      tested. Plasma samples were prospectively collected in a multicenter bio-databank
      from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation
      and a baseline plasma sample. Results: The ddPCR assay detected the exon 11
      mutation in 21 of 22 tumors with exon 11 mutations covered by the assay.
      Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients,
      but in only 1 of 8 patients with localized disease. In serial plasma samples from
      11 patients with metastasized GIST, a decrease in mutant droplets was detected
      during treatment. According to RECIST 1.1, 10 patients had radiological treatment
      response and one patient stable disease. Conclusion: A single ddPCR assay for the
      detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool
      for monitoring treatment response in patients with metastasized GIST and should
      be further evaluated in a larger cohort.

PMID- 29568402
TI  - Structural considerations for functional anti-EGFR * anti-CD3 bispecific
      diabodies in light of domain order and binding affinity.
AB  - We previously reported a functional humanized bispecific diabody (bsDb) that
      targeted EGFR and CD3 (hEx3-Db) and enhancement of its cytotoxicity by
      rearranging the domain order in the V domain. Here, we further dissected the
      effect of domain order in bsDbs on their cross-linking ability and binding
      kinetics to elucidate general rules regarding the design of functional bsDbs.
      Using Ex3-Db as a model system, we first classified the four possible domain
      orders as anti-parallel (where both chimeric single-chain components are variable
      heavy domain (VH)-variable light domain (VL) or VL-VH order) and parallel types
      (both chimeric single-chain components are mixed with VH-VL and VL-VH order).
      Although anti-parallel Ex3-Dbs could cross-link the soluble target antigens,
      their cross-linking ability between soluble targets had no correlation with their
      growth inhibitory effects. In contrast, the binding affinity of one of the two
      constructs with a parallel-arrangement V domain was particularly low, and
      structural modeling supported this phenomenon. Similar results were observed with
      E2x3-Dbs, in which the V region of the anti-EGFR antibody clone in hEx3 was
      replaced with that of another anti-EGFR clone. Only anti-parallel types showed
      affinity-dependent cancer inhibitory effects in each molecule, and E2x3-LH (both
      components in VL-VH order) showed the most intense anti-tumor activity in vitro
      and in vivo. Our results showed that, in addition to rearranging the domain order
      of bsDbs, increasing their binding affinity may be an ideal strategy for
      enhancing the cytotoxicity of anti-parallel constructs and that E2x3-LH is
      particularly attractive as a candidate next-generation anti-cancer drug.

PMID- 29568403
TI  - Exosomal microRNA profiling to identify hypoxia-related biomarkers in prostate
      cancer.
AB  - Hypoxia and expression of hypoxia-related biomarkers are associated with disease
      progression and treatment failure in prostate cancer (PCa). We have reported that
      exosomes (nanovesicles of 30-150 nm in diameter) secreted by human PCa cells
      under hypoxia promote invasiveness and stemness in naive PCa cells. Here, we
      identified the unique microRNAs (miRNAs) loaded in exosomes secreted by PCa cells
      under hypoxia. Using TaqMan(r) array microRNA cards, we analyzed the miRNA
      profile in exosomes secreted by human PCa LNCaP cells under hypoxic (ExoHypoxic)
      and normoxic (ExoNormoxic) conditions. We identified 292 miRNAs loaded in both
      ExoHypoxic and ExoNormoxic. The top 11 miRNAs with significantly higher level in
      ExoHypoxic compared to ExoNormoxic were miR-517a, miR-204, miR-885, miR-143, miR
      335, miR-127, miR-542, miR-433, miR-451, miR-92a and miR-181a; and top nine miRNA
      with significantly lower expression level in ExoHypoxic compared to ExoNormoxic
      were miR-521, miR-27a, miR-324, miR-579, miR-502, miR-222, miR-135b, miR-146a and
      miR-491. Importantly, the two differentially expressed miRNAs miR-885 (increased
      expression) and miR-521 (decreased expression) showed similar expression pattern
      in exosomes isolated from the serum of PCa patients compared to healthy
      individuals. Additionally, miR-204 and miR-222 displayed correlated expression
      patterns in prostate tumors (Pearson R = 0.66, p < 0.0001) by The Cancer Genome
      Atlas (TCGA) prostate adenocarcinoma (PRAD) genomic dataset analysis. Overall,
      the present study identified unique miRNAs with differential expression in
      exosomes secreted from hypoxic PCa cells and suggests their potential usefulness
      as a biomarker of hypoxia in PCa patients.

PMID- 29568404
TI  - Long non-coding RNA XIST as a potential prognostic biomarker in human cancers: a
      meta-analysis.
AB  - Growing studies have confirmed that long non-coding RNAs (lncRNAs) involve in the
      occurrence and development of various cancers. XIST, as a lncRNA, was
      dysregulated in different cancers. This meta-analysis was performed to evaluate
      the prognostic potential of XIST in malignant tumors. Eight databases of PubMed,
      Web of Science, Embase, Cochrane library, CNKI, VIP, SinoMed and Wang Fang were
      comprehensively searched from their initiation date to August 15, 2017. A total
      of nine studies with 853 cancer patients met the including criteria were finally
      included in this meta-analysis after independently screening the literatures by
      two researchers. Any discrepancies were resolved by a consensus. Hazard ratios
      (HRs) with corresponding 95% confidence intervals (CIs) for the primary endpoints
      were extracted and pooled for meta-analysis. Our results showed that expression
      level of XIST was markedly associated with overall survival (function as
      oncogene, HR = 0.53, 95% CI: 0.42-0.68, p < 0.00001; function as tumor
      suppressor, HR = 2.25, 95% CI: 1.15-4.37, p = 0.02), disease free survival
      (DFS)(HR = 0.45; 95% CI: 0.31-0.67, p < 0.0001), tumor type (digestive system
      carcinoma, HR = 0.50; 95% CI: 0.37-0.69, p < 0.00001; non-digestive system
      carcinoma, HR = 0.58; 95% CI: 0.39-0.87, p = 0.008), lymph node metastasis (OR =
      0.32, 95% CI: 0.20-0.52, p < 0.00001), distant metastasis (OR = 0.36, 95% CI:
      0.22-0.60, p < 0.0001) and tumor stage (OR = 0.43, 95% CI: 0.31-0.60, p <
      0.00001). In conclusion, the pooled results in our current work suggest that XIST
      is an important prognostic biomarker in cancer patients.

PMID- 29568405
TI  - Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis.
AB  - Accumulated evidence has shown that the programmed cell death receptor
      1/programmed cell death receptor 1 ligand 1 (PD-1/PD-L1) pathway is a promising
      therapeutic target for cancer immunotherapy. However, the association between PD
      L1 and esophageal squamous cell carcinoma (ESCC) patient survival remains
      unclear. We performed a meta-analysis to investigate the prognostic value of PD
      L1 in ESCC. We searched PubMed, Embase, Web of Knowledge, and Cochrane Central
      Register of Controlled Trials databases for relevant studies that evaluated PD-L1
      expression and ESCC patient survival. Fixed- and random-effects meta-analyses
      were conducted according to the heterogeneity of the included studies.
      Sensitivity analysis was performed according to Metan-based influence analysis.
      Publication bias was evaluated using Egger's and Begg's tests. Overall, 13
      studies with 2,877 patients were included. Twelve studies demonstrated the
      association between overall survival (OS), and 6 studies described the relation
      between disease-free survival (DFS). PD-L1 overexpression was found in 43.7%
      (1,258 of 2,877) of the patients with ESCC. High PD-L1 expression was associated
      with distant metastasis in patients with ESCC (P = 0.04). Moreover, high PD-L1
      expression was significantly associated with poor OS (hazard ratio [HR] 1.38, 95%
      confidence interval [CI] = 1.02-1.86, P = 0.04) and especially in Asian
      populations (HR 1.49, 95% CI = 1.11-1.99, P = 0.008). But it did not have an
      impact on disease-free survival (HR 1.15, 95% CI = 0.76-1.74, P = 0.52). Further
      well-designed clinical studies with uniform assessment approaches for PD-L1
      expression are warranted to verify its prognostic value.

PMID- 29568406
TI  - Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio
      in patients with solid tumors: an updated systemic review and meta-analysis.
AB  - C-reactive protein/albumin ratio (CAR) was originally used as a novel
      inflammation-based prognostic score in predicting outcomes in septic patients.
      Recently, more and more studies have reported the prognostic value of
      pretreatment CAR in solid tumors. However, the results remain controversial
      rather than conclusive. We conducted a meta-analysis based on 24 studies with
      10203 patients to explore the relationship between CAR and survival outcomes in
      patients with solid tumors. The correlation between CAR and clinicopathological
      parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95%
      confidence interval (CI) was applied to be the effect size estimate. The overall
      results showed that elevated CAR was associated with shorter overall survival
      (OS) (including 23 studies and 10067 patients) and poorer disease-free survival
      (DFS) (including 6 studies and 2904 patients). Significant associations between
      high CAR level and poor OS were also found in the subgroup analyses of study
      region, cancer type, primary treatment, clinical stage, cut-off selection, sample
      size, and cut-off value. Moreover, subgroup analyses demonstrated that study
      region, primary treatment, clinical stage, sample size, and cut-off value did not
      alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was
      correlated with certain phenotypes of tumor aggressiveness, such as poor
      histological grade, serious clinical stage, advanced tumor depth, positive lymph
      node metastasis, and positive distant metastasis. Together, our meta-analysis
      suggests that elevated level of serum CAR predicts worse survival and unfavorable
      clinical characteristics in cancer patients, and CAR may serve as an effective
      prognostic factor for solid tumors.

PMID- 29568407
TI  - MiR-486 as an effective biomarker in cancer diagnosis and prognosis: a systematic
      review and meta-analysis.
AB  - Purpose: MiR-486 was found to be associated with cancer's diagnosis and
      prognosis. This meta-analysis aimed to investigate the potential effect of miR
      486 on cancer detection and prognosis. Materials and Methods: We searched PubMed,
      Cochrane library, Embase, Chinese National Knowledge Infrastructure (CNKI) and
      Wanfang databases to find all correlated articles. The STATA 11.0 was applied to
      estimate the pooled effects, heterogeneity and publication bias. Results: The
      pooled sensitivity (SEN), specificity (SPE) and Area under the curve (AUC) were
      82% (95% CI: 78-85%), 88% (95% CI: 83-92%) and 0.91 (95% CI: 0.88-0.93). Subgroup
      analysis indicated miR-486 from circulating samples exhibited higher diagnostic
      accuracy with the AUC was 0.90 (95% CI: 0.87-0.92) than miR-486 from other
      specimen with the AUC of 0.78 (95% CI: 0.75-0.82) and miR-486 obtained a better
      diagnostic value in the Asian population with the AUC of 0.94 (95% CI: 0.91-0.95)
      than the Caucasian and Caucasian/African population with the AUC of 0.80 (95% CI:
      0.76-0.83) and 0.89 (95% CI: 0.86-0.91) respectively. MiR-486 obtained high value
      for the diagnosis of non-small cell lung cancer with SEN, SPE and AUC were 0.82
      (95% CI: 0.0.77-0.87), 0.90 (95% CI: 0.84-0.94) as well as 0.92 (95% CI: 0.89
      0.94) respectively. For the 7 prognostic tests, the pooled hazard ratio (HR) was
      0.48 (95% CI: -0.13-1.08) for low versus high miR-486 expression. Conclusions:
      This meta-analysis indicated that miR-486 can be used as ideal biomarkers in the
      cancer's diagnosis. However, Low miR-486 expression did not increase the risk of
      poor outcome.

PMID- 29568408
TI  - Association of body mass index with mortality and postoperative survival in renal
      cell cancer patients, a meta-analysis.
AB  - Obesity is one of the major risk factors of cancer. However, how body mass index
      (BMI) influences the prognosis of renal cell cancer (RCC) patient is unclear. In
      this work, we have performed a meta-analysis to elucidate the role of abnormal
      weight in RCC mortality and postoperative survival. Articles related to BMI and
      RCC mortality as well as postoperative survival has been identified by searching
      PUBMED and ENBASE. Totally, 19 articles have been selected for this meta
      analysis, 5 articles for RCC mortality and 14 for postoperative survival.
      Compared to normal weight, the estimated relative risks of RCC mortality are 0.71
      (95% CI: 0.34-1.49), 1.19 (95% CI: 1.05-1.35) and 1.71 (95% CI: 1.27-2.00)
      respectively for the underweight, overweight and obesity patients. The risk of
      RCC mortality increase 5% for each 1 kg/m2 increment of BMI. However, the
      estimated hazard ratios of cancer specific postoperative survival are 2.62 (95%
      CI: 1.67-4.11), 0.72 (95% CI: 0.63-0.83) and 0.66 (95% CI: 0.49-0.89)
      respectively for underweight, overweight and obesity RCC patients. The risk of
      hazard ratio decrease 5% for each 1 kg/m2 increment of BMI. In addition, the
      hazard ratios of postoperative overall survival show a similar tendency. These
      results indicate an opposite association of BMI with mortality and postoperative
      survival in renal cell cancer patients.

PMID- 29568409
TI  - Combined value of red blood cell distribution width and global registry of acute
      coronary events risk score on predicting long-term major adverse cardiac events
      in STEMI patients undergoing primary PCI.
AB  - The combined value of RDW and GRACE risk score for cardiovascular prognosis in ST
      segment elevation myocardial infarction (STEMI) undergoing primary percutaneous
      coronary intervention (PCI) has not been fully investigated. This study was
      designed to explore the combined value of RDW and GRACE risk score on predicting
      long-term major adverse cardiac event (Mace) in STEMI patients undergoing primary
      PCI. This study included 390 STEMI patients. The primary endpoint at the (33.5 +/
      7.1) months follow-up was composed of cardiac death and nonfatal myocardial
      infarction. The relationship between clinical parameters and clinical outcomes
      was evaluated using Cox regression model and receiver operating characteristic
      (ROC) analysis. Mace occurred in 126 (32.3%) patients including 54 (13.8%)
      cardiac deaths and 72 (18.5%) nonfatal myocardial infarctions. Patients in Mace
      group had significantly higher RDW and GRACE score than the patients in non-Mace
      group. According to the Cox model, RDW and GRACE score were the most important
      independent predictors of Mace and cardiac death. The best cut-off value for RDW
      to predict the occurrence of primary events was 13.25% (AUC = 0.694, 95% CI:0.639
      0.750, P < 0.001) and that for GRACE score was 119.5 (AUC = 0.721, 95% CI:0.666
      0.777, P < 0.001). The combination of RDW and GRACE score were more valuable (AUC
      = 0.775, 95% CI: 0.727-0.824, P < 0.001). Kaplan-Meier analysis provided
      significant prognostic information with the highest risk for cardiac death (Log
      Rank chi2 = 24.684, P < 0.001) in group with both high RDW (> 13.25%) and high
      GRACE score (> 119.5). The combination of RDW level and GRACE score may be
      valuable and simple independent predictors of Mace and cardiac death in STEMI
      patients undergoing primary PCI. They may be useful tools for risk stratification
      and may indicate long-term clinical outcomes.

PMID- 29568410
TI  - Prevalence of non-syndromic orofacial clefts: based on 15,094,978 Chinese
      perinatal infants.
AB  - Non-syndromic orofacial clefts (NSOFC), which include cleft lip and palate (CLP),
      cleft lip only (CLO), and cleft palate only (CPO), contains a range of disorders
      affecting the lips and oral cavity. No systematic review and meta-analysis has
      been carried out to synthesize the prevalence of NSOFC in Chinese perinatal
      infants. We aimed to quantify and understand the variation of prevalence national
      and regional levels. Four English databases and four Chinese databases were
      searched using a comprehensive search strategy from inception to April 2017. The
      random effect model was used for this meta-analysis. To determine the sources of
      heterogeneity, subgroup analyses and meta-regression were conducted based on
      different categories. The protocol has been pre-registered in the PROSPERO,
      number CRD42017062293. 110 studies, including 15,094,978 Chinese perinatal
      infants, were eligible for inclusion. The pooled prevalence rate for NSOFC was
      1.670/00 (95% CI 1.53-1.82), varying with provinces. The pooled prevalence
      estimate was 0.560/00 (0.50-0.63) for CLO, 0.820/00 (0.73-0.90) for CLP, and
      0.270/00 (0.24-0.30) for CPO. Significant associations were found between overall
      prevalence estimates and survey year and study region. The prevalence of NSOFC
      was severe in Chinese perinatal infants, varying with provinces. The results will
      serve as a baseline for future assessment of the overall effectiveness of NSOFC
      control, and will also support and inform health policy for planning and helping
      health debates.

PMID- 29568411
TI  - The development of CAR design for tumor CAR-T cell therapy.
AB  - In recent years, the chimeric antigen receptor modified T cells (Chimeric antigen
      receptor T cells, CAR-T) immunotherapy has developed rapidly, which has been
      considered the most promising therapy. Efforts to enhance the efficacy of CAR
      based anti-tumor therapy have been made, such as the improvement of structures of
      CAR-T cells, including the development of extracellular antigen recognition
      receptors, intracellular co-stimulatory molecules and the combination application
      of CARs and synthetic small molecules. In addition, effects on the function of
      the CAR-T cells that the space distance between the antigen binding domains and
      tumor targets and the length of the spacer domains have are also being
      investigated. Given the fast-moving nature of this field, it is necessary to make
      a summary of the development of CAR-T cells. In this review, we mainly focus on
      the present design strategies of CAR-T cells with the hope that they can provide
      insights to increase the anti-tumor efficacy and safety.

PMID- 29568413
TI  - Performance evaluation method for read mapping tool in clinical panel sequencing.
AB  - In addition to the rapid advancement in Next-Generation Sequencing (NGS)
      technology, clinical panel sequencing is being used increasingly in clinical
      studies and tests. However, tools that are used in NGS data analysis have not
      been comparatively evaluated in performance for panel sequencing. This study
      aimed to evaluate the tools used in the alignment process, the first procedure in
      bioinformatics analysis, by comparing tools that have been widely used with ones
      that have been introduced recently. With the accumulated panel sequencing data,
      detected variant lists were cataloged and inserted into simulated reads produced
      from the reference genome (h19). The amount of unmapped reads and misaligned
      reads, mapping quality distribution, and runtime were measured as standards for
      comparison. As the most widely used tools, Bowtie2 and BWA-MEM each showed
      explicit performance with AUC of 0.9984 and 0.9970 respectively. Kart,
      maintaining superior runtime and less number of misaligned read, also similarly
      possessed high level of AUC (0.9723). Such selection and optimization method of
      tools appropriate for panel sequencing can be utilized for fields requiring error
      minimization, such as clinical application and liquid biopsy studies.

PMID- 29568414
TI  - Comparative genomic analysis of Lactobacillus plantarum GB-LP4 and identification
      of evolutionarily divergent genes in high-osmolarity environment.
AB  - Lactobacillus plantarum is one of the widely-used probiotics and there have been
      a large number of advanced researches on the effectiveness of this species.
      However, the difference between previously reported plantarum strains, and the
      source of genomic variation among the strains were not clearly specified. In
      order to understand further on the molecular basis of L. plantarum on Korean
      traditional fermentation, we isolated the L. plantarum GB-LP4 from Korean
      fermented vegetable and conducted whole genome assembly. With comparative
      genomics approach, we identified the candidate genes that are expected to have
      undergone evolutionary acceleration. These genes have been reported to associate
      with the maintaining homeostasis, which are generally known to overcome
      instability in external environment including low pH or high osmotic pressure.
      Here, our results provide an evolutionary relationship between L. plantarum
      species and elucidate the candidate genes that play a pivotal role in
      evolutionary acceleration of GB-LP4 in high osmolarity environment. This study
      may provide guidance for further studies on L. plantarum.

PMID- 29568415
TI  - Dynamic light sheet generation and fluorescence imaging behind turbid media.
AB  - Background: Light sheet microscopy became a popular tool allowing fast imaging
      with reduced out of focus light. However, when light penetrates turbid media such
      as biological tissues, multiple scattering scrambles the illumination into a
      speckle pattern and severely challenges conventional fluorescence imaging with
      focused light or with a light sheet. In this article, we present generation of
      light sheet type illumination patterns despite scattering. Methods: We optimize
      the wave-front of the incoming light to transform the speckle pattern behind the
      scattering layer into a light sheet within the region of interest. We utilize a
      fast spatial light modulator for phase modulation and a genetic optimization
      algorithm. The light pattern behind the scattering layer is detected via a clear
      detection path and acts as a feedback signal for the algorithm. Results: We
      enabled homogenous light sheet illumination behind turbid media and enhanced the
      signal of fluorescent beads selectively at the desired focal plane up to eight
      times on average. The technique is capable to compensate the dynamic changes of
      the speckle pattern as well, as shown on samples consisting of living drosophila
      pupae. Conclusion: Our technique shows that not only single foci, but also a
      homogenous light sheet illumination can directly be created and maintained behind
      static and dynamic scattering media. To make the technique suitable for common
      biological settings, where the detection path is turbid as well, a fluorescent
      probe can be used to provide the feedback signal.

PMID- 29568412
TI  - Impact of physical exercise in cancer survivors during and after antineoplastic
      treatments.
AB  - Cancer patients experience symptoms and adverse effects of treatments that may
      last even after the end of treatments. Exercise is a safe, non-pharmacological
      and cost-effective therapy that can provide several health benefits in cancer
      patient and survivors, reducing cancer symptoms and cancer treatment side
      effects. The purpose of this review is to describe how the physical exercise is
      capable to reduce cancer symptoms and cancer treatment side effects. We realized
      a pragmatic classification of symptoms, dividing them into physical,
      psychological and psycho-physical aspects. For each symptom we discuss causes,
      therapies, we analyse the effects of physical exercise and we summarize the most
      effective type of exercise to reduce the symptoms. This review also points out
      what are the difficulties that patients and survivors face during the practice of
      physical activity and provides some solutions to overcome these barriers. Related
      to each specific cancer, it emerges that type, frequency and intensity of
      physical exercise could be prescribed and supervised as a therapeutic program,
      like it occurs for the type, dose and duration of a drug treatment.

PMID- 29568416
TI  - Does the thermal evolution of molecular structures critically affect the magnetic
      anisotropy?
AB  - A dysprosium based single-ion magnet is synthesized and characterized by the
      angular dependence of the single-crystal magnetic susceptibility. Ab initio and
      effective electrostatic analyses are performed using the molecular structures
      determined from single crystal X-ray diffraction at 20 K, 100 K and 300 K.
      Contrary to the common assumption, the results reveal that the structural thermal
      effects that may affect the energy level scheme and magnetic anisotropy below 100
      K are negligible.

PMID- 29568417
TI  - Bidirectional photoswitching of magnetic properties at room temperature: ligand
      driven light-induced valence tautomerism.
AB  - Valence tautomeric (VT) metal complexes are highly promising bistable molecular
      compounds for applications as molecular switches in molecular electronics and
      spintronics. Although VT species can be switched with light, the photoswitching
      in all reported systems requires very low temperatures (usually below 20 K)
      because photoinduced states are highly unstable at room temperature. The thermal
      instability hinders any practical application of these complexes in genuine
      devices. In this report, for the first time we demonstrate photoswitching of VT
      species and associated magnetic properties at room temperature. The bidirectional
      photoswitching in solution is due to cis-trans photoisomerizable 4-styrylpyridine
      ligands deliberately integrated into cobalt dioxolene molecular complexes. The
      novel type of photoswitching has been coined Ligand-Driven Light-Induced Valence
      Tautomerism (LD-LIVT). The photoconversion of VT states of 28% has been achieved
      in solution at room temperature. The photoinduced states show extraordinary
      thermal stability for hours at room temperature, as compared to common
      nanoseconds reported previously. The switching proceeds at molecular level with
      the effective photoswitching rate of 3 * 1013 molecules per s under our
      conditions. Consequently, this work may open new horizons in applications of
      molecular switches based on VT metal complexes in molecular devices functioning
      at room temperature.

PMID- 29568418
TI  - Selective and sensitive visualization of endogenous nitric oxide in living cells
      and animals by a Si-rhodamine deoxylactam-based near-infrared fluorescent probe.
AB  - Nitric oxide (NO) is a fundamental signaling molecule that regulates virtually
      every critical cellular function, and it is also a potent mediator of cellular
      damage in a wide range of conditions mainly via its secondary metabolite
      peroxynitrite (ONOO-). In this work, we present an o-phenylenediamine (OPD)
      locked Si-rhodamine deoxylactam, i.e.deOxy-DALSiR, as a near-infrared fluorescent
      probe for the selective and sensitive detection of NO in living cells and bodies.
      Not only could the probe overcome the limitations suffered by widely used and
      commercialized OPD-type fluorescent NO probes, such as the possible interferences
      by dehydroascorbic acid/ascorbic acid/methylglyoxal (DHA/AA/MGO), pH-sensitive
      fluorescence output, and short excitation and emission wavelengths, but it can
      also avoid serious interference from cysteine (Cys) found in the rhodamine lactam
      based fluorescent NO probes developed later. What's more, the probe is fairly
      sensitive for NO, as evidenced by its rapid fluorescence response rate (within
      seconds), huge fluorescence off-on ratio (6300-fold), and ultra-low detection
      limit (0.12 nM). Its effectiveness and practicability have been demonstrated by
      the successful imaging of endogenous NO in RAW 264.7 macrophages, pancreatic beta
      cells, and endothelial EA.hy926 cells, as well as in inflamed and diabetic mouse
      models.

PMID- 29568419
TI  - Multifunctional (3-in-1) cancer theranostics applications of hydroxyquinoline
      appended polyfluorene nanoparticles.
AB  - The accumulation of fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ)
      nanoparticles and their utility for multi-color bio-imaging and drug delivery for
      cancer treatment are reported. The formation of nanoparticles (PF-HQ) containing
      hydrophobic pockets via three-dimensional growth of a polymeric backbone in a
      higher water fraction (THF : H2O = 1 : 9) was observed. The nanoparticles showed
      incredible dual-state optical and fluorescence properties, which were further
      explored in multi-color cell imaging in both cancer and normal cells. The cell
      viability assay in various normal cells confirmed the biocompatible nature of PF
      HQ, which was further supported by an ex vivo (chick chorioallantoic membrane
      assay) model. This encouraged us to fabricate PF-HQ-based new drug delivery
      systems (DDS: PF-HQ-DOX) upon conjugation with the FDA-approved anti-cancer drug
      doxorubicin (DOX) by filling the hydrophobic pockets of the polymer
      nanoparticles. The enhanced anti-cancer activity of the DDS (PF-HQ-DOX) compared
      with that of free DOX was observed in mouse melanoma cancer cells (B16F10) and a
      subcutaneous mouse (C57BL6/J) melanoma tumor model upon administration of PF-HQ
      DOX. Ex vivo biodistribution studies using a fluorescence quantification method
      demonstrated the enhanced accumulation of DOX in tumor tissues in the PF-HQ-DOX
      treated group compared to that of the free drug, signifying the drug delivery
      efficacy of the delivery system by a passive targeting manner. Based on the above
      biological data (in vitro and in the pre-clinical model), these robust and
      versatile fluorescent hydroxyquinoline-affixed polyfluorene (PF-HQ) nanoparticles
      could be effectively utilized for multifunctional biomedical applications (as
      they are biocompatible and can be used for bio-imaging and as a drug delivery
      vehicle).

PMID- 29568420
TI  - Achieving enhanced cell penetration of short conformationally constrained
      peptides through amphiphilicity tuning.
AB  - Due to their enhanced stability and cell permeability, cyclic cell-penetrating
      peptides have been widely used as delivery vectors for transporting cell
      impermeable cargos into cells. In this study, we synthesized a panel of
      conformationally constrained peptides with either alpha-helix or beta-hairpin
      conformations. We tuned the amphiphilicity of these constrained peptides with
      different distributions of charged or hydrophobic residues and compared their
      cellular uptake efficiencies in different cell lines. We found that the
      amphipathicity of these conformationally constrained peptides correlates well
      with their cellular uptake efficiency. We proposed that peptides with larger
      hydrophobic moments (HMs) have stronger binding affinities with the cell membrane
      which further accelerates the endocytosis process. This finding should provide an
      approach towards the design of more potent conformationally constrained cell
      penetrating peptides for biomedical applications.

PMID- 29568421
TI  - Simultaneous quantification of multiple endogenous biothiols in single living
      cells by plasmonic Raman probes.
AB  - Intracellular biothiols mediate many important physiological and pathological
      processes. Due to their low content and competing thiol-reactivity, it is still
      an unmet challenge to quantify them within a complicated intracellular
      environment. Herein, we demonstrated a strategy to discriminate three biothiols,
      i.e. cysteine (Cys), homo-cysteine (Hcy) and glutathione (GSH), and quantify
      their concentrations within single living cells, using one platform of Raman
      probe. By monitoring the reaction kinetics of biothiols with Raman probes and
      discriminating their products with a quantitative principal component analysis
      (qPCA) method, these three biothiols could be simultaneously quantified in both
      cell lysis and single living cells. The concentrations of Cys, Hcy and GSH in
      single Hela cells were 158 +/- 19 MUM, 546 +/- 67 MUM and 5.07 +/- 0.62 mM,
      respectively, which gives the precise concentrations of these three biothiols at
      a single cell level for the first time. This method provides a general strategy
      for discriminating each component from a mixed system and has potential for
      quantifying any biomolecules within an in vitro or in vivo biological
      environment.

PMID- 29568422
TI  - Michael addition-based probes for ratiometric fluorescence imaging of protein S
      depalmitoylases in live cells and tissues.
AB  - The reversible modification of cysteine residues through thioester formation with
      palmitate (protein S-palmitoylation) is a prevalent chemical modification that
      regulates the function, localization, and stability of many proteins. Current
      methods for monitoring the "erasers" of S-palmitoylation, acyl-protein
      thioesterases (APTs), rely on destructive proteomic methods or "turn-on" probes,
      precluding deployment in heterogeneous samples such as primary tissues. To
      address these challenges, we present the design, synthesis, and biological
      evaluation of Ratiometric Depalmitoylation Probes (RDPs). RDPs respond to APTs
      with a robust ratiometric change in fluorescent signal both in vitro and in live
      cells. Moreover, RDPs can monitor endogenous APT activities in heterogeneous
      primary human tissues such as colon organoids, presaging the utility of these
      molecules in uncovering novel roles for APTs in metabolic regulation.

PMID- 29568423
TI  - An acidic pH independent piperazine-TPE AIEgen as a unique bioprobe for lysosome
      tracing.
AB  - Lysosomes are involved in a multitude of cellular processes and their dysfunction
      is associated with various diseases. They are the most acidic organelles (pH 3.8
      6.6, size 0.1-1.2 MUm) with the highest viscosity (47-190 cP at 25  degrees C) in
      the cell. Because of their acidity, pH dependent non-AIE active fluorescent
      lysosomal probes have been developed that rely on protonation inhibited
      photoinduced electron transfer (PET). In this work, an acidic pH independent
      lysosome targetable piperazine-TPE (PIP-TPE) AIEgen has been designed with unique
      photophysical properties making it a suitable probe for quantifying viscosity. In
      a non-aggregated state PIP-TPE shows deep-blue emission as opposed to its
      yellowish-green emission in the bulk. It possesses high specificity for lysosomes
      with negligible cytotoxicity and good tracing ability due to its better
      photostability compared to LysoTracker Red. In contrast to most known lysosome
      probes that rely solely on PET, restriction of intramolecular motion (RIM) due to
      the larger viscosity inside the lysosomes is the mechanism responsible for PIP
      TPE's fluorescence. PIP-TPE's high selectivity is attributed to its unique
      molecular design that features piperazine fragments providing a perfect balance
      between lipophilicity and polarity.

PMID- 29568424
TI  - Optical control of GPR40 signalling in pancreatic beta-cells.
AB  - Fatty acids activate GPR40 and K+ channels to modulate beta-cell function.
      Herein, we describe the design and synthesis of FAAzo-10, a light-controllable
      GPR40 agonist based on Gw-9508. FAAzo-10 is a potent GPR40 agonist in the trans
      configuration and can be inactivated on isomerization to cis with UV-A light.
      Irradiation with blue light reverses this effect, allowing FAAzo-10 activity to
      be cycled ON and OFF with a high degree of spatiotemporal precision. In
      dissociated primary mouse beta-cells, FAAzo-10 also inactivates voltage-activated
      and ATP-sensitive K+ channels, and allows us to control glucose-stimulated Ca2+
      oscillations in whole islets with light. As such, FAAzo-10 is a useful tool to
      study the complex effects, with high specificity, which FA-derivatives such as Gw
      9508 exert at multiple targets in mouse beta-cells.

PMID- 29568425
TI  - A functionalized metal-organic framework decorated with O- groups showing
      excellent performance for lead(ii) removal from aqueous solution.
AB  - Heavy metal ions are highly toxic and widely spread as environmental pollutants.
      New strategies are being developed to efficiently remove these toxic ions.
      Herein, we use the intrinsic advantages of metal-organic frameworks (MOFs) and
      develop a porous Zn(ii)-based MOF decorated with O- groups for the removal of
      Pb2+. Benefiting from its multiple porosity, sufficient adsorption sites and
      strong affinity, the activated MOF material exhibits an ultrahigh Pb2+ uptake
      capacity (616.64 mg g-1), surpassing all those of reported MOF adsorbents.
      Moreover, it can selectively capture Pb2+ with high efficiency (>99.27%) against
      background ions. Even in the presence of a high concentration of competitive
      ions, such as Ca2+ or Mg2+, effective removal (>99.21%) can also be achieved in a
      short time. The excellent removal performance demonstrates the strong
      electrostatic attraction and coordination interaction between the highly
      accessible O- groups and Pb2+. The possible adsorption mechanism was
      systematically verified by zeta potential, FT-IR and XPS studies. Our work
      reveals the enormous potential of functionalized MOFs as an appealing platform to
      construct sorbent materials.

PMID- 29568426
TI  - Towards quantifying the role of hydrogen bonding within amphiphile self
      association and resultant aggregate formation.
AB  - Herein, we present a series of five tetrabutylammonium (TBA) sulfonate-urea
      amphiphilic salts. In solution these amphiphilic salts have been shown to form a
      variety of self-associated species. The proportion and type of which are both
      solvent and concentration dependent. In DMSO-d6 a variety of NMR experiments
      provide evidence towards the formation of mainly dimeric over larger aggregate
      species. Increasing the percentage of water was shown to increase the
      concentration of the larger aggregates over dimers in solution. A correlation was
      established between critical micelle concentration (CMC) values obtained in a 1 :
      19 EtOH : H2O mixture, dimeric self-association constants obtained in a DMSO-d6 -
      0.5% H2O and the results of simple semi-empirical PM6 computational modelling
      methods. This approach begins to quantify the role of hydrogen bonding in
      amphiphile self-association and the effects it imparts on surfactant properties.
      This consequently provides preliminary evidence that these properties maybe
      predicted by simple low level computational modelling techniques.

PMID- 29568427
TI  - Nanomolar small-molecule detection using a genetically encoded 129Xe NMR contrast
      agent.
AB  - Genetically encoded magnetic resonance imaging (MRI) contrast agents enable non
      invasive detection of specific biomarkers in vivo. Here, we employed the hyper
      CEST 129Xe NMR technique to quantify maltose (32 nM to 1 mM) through its
      modulation of conformational change and xenon exchange in maltose binding protein
      (MBP). Remarkably, no hyper-CEST signal was observed for MBP in the absence of
      maltose, making MBP an ultrasensitive "smart" contrast agent. The resonance
      frequency of 129Xe bound to MBP was greatly downfield-shifted (Deltadelta = 95
      ppm) from the 129Xe(aq) peak, which facilitated detection in E. coli as well as
      multiplexing with TEM-1 beta-lactamase. Finally, a Val to Ala mutation at the MBP
      Xe binding site yielded 34% more contrast than WT, with 129Xe resonance frequency
      shifted 59 ppm upfield from WT. We conclude that engineered MBPs constitute a new
      class of genetically encoded, analyte-sensitive molecular imaging agents
      detectable by 129Xe NMR/MRI.

PMID- 29568429
TI  - Intramolecular substitution uncages fluorogenic probes for detection of metallo
      carbapenemase-expressing bacteria.
AB  - This work reports a novel caging strategy for designing fluorogenic probes to
      detect the activity of beta-lactamases. The caging strategy uses a thiophenyl
      linker connected to a fluorophore caged by a good leaving group-dinitrophenyl.
      The uncaging proceeds in two steps through the sulfa-releasing and subsequent
      intramolecular substitution. The length of the linker has been examined and
      optimized to maximize the rate of intramolecular reaction and thus the rate of
      fluorescence activation. Finally based on this strategy, we prepared a green
      fluorogenic probe CAT-7 and validated its selectivity for detecting metallo
      carbapenemases (VIM-27, IMP-1, NDM-1) in carbapenem-resistant Enterobacteriaceae
      (CRE) lysates.

PMID- 29568428
TI  - Formylation or methylation: what determines the chemoselectivity of the reaction
      of amine, CO2, and hydrosilane catalyzed by 1,3,2-diazaphospholene?
AB  - DFT computations have been performed to gain insight into the mechanisms of
      formylation/methylation of amines (e.g. methylaniline (1a)/2,2,4,4
      tetramethylpiperidine (2a)) with CO2 and hydrosilane ([Si]H2, [Si] = Ph2Si),
      catalyzed by 1,3,2-diazaphospholene ([NHP]H). Different from the generally
      proposed sequential mechanism for the methylation of amine with CO2, i.e.
      methylation proceeds via formylation, followed by further reduction of formamide
      to give an N-methylated amine, the study characterized a competition mechanism
      between formylation and methylation. The chemoselectivity originates from the
      competition between the amine and [NHP]H hydride to attack the formyloxy carbon
      of [Si](OCHO)2 (the insertion product of CO2 into [Si]H2). When the attack of an
      amine (e.g.1a) wins, the transformation affords formamide (1b) but would
      otherwise (e.g.2a) result in an N-methylated amine (2c). The reduction of
      formamide by [Si]H2 or [NHP]H is highly unfavorable kinetically, thus we call
      attention to the sequential mechanism for understanding the methylation of amine
      with CO2. In addition, the study has the following key mechanistic findings. The
      activation of CO2 by [NHP]H establishes an equilibrium: [NHP]H + CO2 ? [NHP]OCHO
      ? [NHP]+ + HCO2-. The ions play catalytic roles to promote formylation via HCO2-
      or methylation via[NHP]+ . In 1a formylation, HCO2- initiates the reaction,
      giving 1b and silanol byproducts. However, after the initiation, the silanol
      byproducts acting as hydrogen transfer shuttles are more effective than HCO2- to
      promote formylation. In 2a methylation, [NHP]+ promotes the generation of the key
      species, formaldehyde and a carbocation species (IM17+ ). Our experimental study
      corroborates our computed mechanisms.

PMID- 29568430
TI  - Selective inhibition of cancer cells by enzyme-induced gain of function of
      phosphorylated melittin analogues.
AB  - The selective killing of cancer cells and the avoidance of drug resistance are
      still difficult challenges in cancer therapy. Here, we report a new strategy that
      uses enzyme-induced gain of function (EIGF) to regulate the structure and
      function of phosphorylated melittin analogues (MelAs). Original MelAs have the
      capacity to disrupt plasma membranes and induce cell death without selectivity.
      However, phosphorylation of Thr23 on one of the MelAs (MelA2-P) efficiently
      ameliorated the membrane lysis potency as well as the cytotoxicity for normal
      mammalian cells. After treatment with alkaline phosphatase (ALP), which is more
      active in cancer cells than normal cells, MelA2-P restored the pore-forming
      function around the cancer cells and induced cancer cell death selectively. This
      mechanism was independent of the receptor proteins and the cell uptake process,
      which may partially bypass the development of drug resistance in cancer cells.

PMID- 29568431
TI  - Electrochemical recognition and quantification of cytochrome c expression in
      Bacillus subtilis and aerobe/anaerobe Escherichia coli using N,N,N',N'
      tetramethyl-para-phenylene-diamine (TMPD).
AB  - The colorimetric identification of pathogenic and non-pathogenic bacteria in cell
      culture is commonly performed using the redox mediator N,N,N',N'-tetramethyl-para
      phenylene-diamine (TMPD) in the so-called oxidase test, which indicates the
      presence of bacterial cytochrome c oxidases. The presented study demonstrates the
      ability of electrochemistry to employ TMPD to detect bacteria and quantify the
      activity of bacterial cytochrome c oxidases. Cyclic voltammetry studies and
      chronoamperometry measurements performed on the model organism Bacillus subtilis
      result in a turnover number, calculated for single bacteria. Furthermore, trace
      amounts of cytochrome c oxidases were revealed in aerobically cultured
      Escherichia coli, which to our knowledge no other technique is currently able to
      quantify in molecular biology. The reported technique could be applied to a
      variety of pathogenic bacteria and has the potential to be employed in future
      biosensing technology.

PMID- 29568432
TI  - Addressing the autofluorescence issue in deep tissue imaging by two-photon
      microscopy: the significance of far-red emitting dyes.
AB  - The fluorescence imaging of tissue is essential for studying biological events
      beyond the cellular level. Two-photon microscopy based on the nonlinear light
      absorption of fluorescent dyes is a viable tool for the high resolution imaging
      of tissue. A key limitation for deep tissue imaging is the autofluorescence from
      intrinsic biomolecules. Here, we report a systematic study that discloses
      relative autofluorescence interference, which is dependent on the type of tissue
      and the excitation and emission wavelengths in two-photon imaging. Among the
      brain, kidney, liver, lung, and spleen mouse tissues examined, the kidney tissue
      exhibited prominent autofluorescence followed by the liver and others. Notably,
      regardless of the tissue type, prominent autofluorescence is observed not only
      from the green emission channel but also from the yellow emission channel where
      common two-photon absorbing dyes also emit, whereas there is minimal
      autofluorescence from the red channel. The autofluorescence is slightly
      influenced by the excitation wavelength. Toward minimal autofluorescence, we
      developed a new class of two-photon absorbing dyes that are far-red emitting,
      water-soluble, and very bright inside cells as well as in tissue. A comparative
      assessment of the imaging depth, which is dependent on the three selected dyes
      that emit in the blue-green, yellow, and far-red regions, shows the importance of
      far-red emitting dyes for deep tissue imaging.

PMID- 29568433
TI  - Synthetic upcycling of polyacrylates through organocatalyzed post-polymerization
      modification.
AB  - The direct transformation of commercially available commodity polyacrylates into
      value-added materials was achieved. We demonstrate how 1,5,7
      triazabicyclo[4.4.0]dec-5-ene, serving as a nucleophilic catalyst, can be used to
      catalyze acyl substitution reactions of acrylic polymers in the presence of
      alcohol and amine nucleophiles. Furthermore, we found that organocatalytic
      transesterification exhibits high selectivity towards sterically unhindered
      esters, thus providing a new route towards site-selective acyl substitution of
      macromolecular materials. Combining this methodology with reversible-deactivation
      radical polymerization (RDRP) techniques such as reversible addition
      fragmentation chain-transfer (RAFT) polymerization allowed for the precise
      functionalization of sterically-differentiated acrylic copolymers and polymeric
      chain ends. We envision this approach to expedite functional polymer synthesis
      and provide access to functional macromolecules prepared from inexpensive,
      hydrolytically-stable polymeric precursors.

PMID- 29568434
TI  - Tuning the stereo-hindrance of a curcumin scaffold for the selective imaging of
      the soluble forms of amyloid beta species.
AB  - Amyloid peptides and proteins are associated with the pathologies of numerous
      diseases. In the progression of a disease, amyloids exist in soluble and
      insoluble forms, which are the dominant species at different stages of the
      disease and they have different degrees of toxicity. However, differentiating
      between the soluble and insoluble forms is very challenging with small molecule
      probes due to multiple obstacles that need to be overcome. Inspired by the
      recognition principle of antibodies for sAbeta, we hypothesized that the
      accessibility/tightness of soluble and insoluble amyloids could be utilized to
      design imaging probes to recognize different amyloid forms and the stereo
      hindrance tuning strategy could be used to design imaging probes for selectively
      detecting the soluble amyloid beta (sAbeta) species in Alzheimer's disease (AD).
      Herein, we demonstrated that tuning the stereo-hindrance of the phenoxy-alkyl
      chains at the 4-position of a curcumin scaffold could lead to certain selectivity
      for sAbeta over insoluble Abetas (insAbeta). Among the designed compounds, CRANAD
      102 showed a 68-fold higher affinity for sAbeta than for insAbeta (7.5 +/- 10 nM
      vs. 505.9 +/- 275.9 nM). Moreover, our imaging data indicated that CRANAD-102 was
      indeed capable of detecting sAbeta in vivo using 4 month old APP/PS1 mice, in
      which sAbeta is the predominant species in the brain. In addition, we also
      demonstrated that CRANAD-102 could be used to monitor the increase in sAbeta
      loading from the ages of 4 months old to 12 months old. We believe that CRANAD
      102 can be a useful probe for selectively detecting sAbeta species in AD and that
      our probe designing strategy can be applied to other amyloids and will have
      tremendous impact on AD drug development and other amyloid research.

PMID- 29568435
TI  - Influence of axle length on the rate and mechanism of shuttling in rigid H-shaped
      [2]rotaxanes.
AB  - A series of [2]rotaxane molecular shuttles was prepared containing a
      dibenzo[24]crown-8 (DB24C8) wheel and a rigid H-shaped axle with varying track
      lengths between recognition sites; from 7.4 to 20.3 A as defined by 1-4 phenyl
      rings or a naphthyl group. The rate of shuttling was measured by variable
      temperature 1H NMR spectroscopy for neutral compounds and EXSY experiments for
      dicationic species. The rates were found to be independent of the length of the
      axle, except when the distance between the two recognition sites might be short
      enough (n = 1) to allow the crown ether to simultaneously interact with both
      recognition sites providing a short-cut mechanism which could lower the energy
      barrier. This notion is supported by DFT calculations and solid-state
      characterization of model compounds that mimic possible transition states.

PMID- 29568436
TI  - A structural examination and collision cross section database for over 500
      metabolites and xenobiotics using drift tube ion mobility spectrometry.
AB  - The confident identification of metabolites and xenobiotics in biological and
      environmental studies is an analytical challenge due to their immense dynamic
      range, vast chemical space and structural diversity. Ion mobility spectrometry
      (IMS) is widely used for small molecule analyses since it can separate isomeric
      species and be easily coupled with front end separations and mass spectrometry
      for multidimensional characterizations. However, to date IMS metabolomic and
      exposomic studies have been limited by an inadequate number of accurate collision
      cross section (CCS) values for small molecules, causing features to be detected
      but not confidently identified. In this work, we utilized drift tube IMS (DTIMS)
      to directly measure CCS values for over 500 small molecules including primary
      metabolites, secondary metabolites and xenobiotics. Since DTIMS measurements do
      not need calibrant ions or calibration like some other IMS techniques, they avoid
      calibration errors which can cause problems in distinguishing structurally
      similar molecules. All measurements were performed in triplicate in both positive
      and negative polarities with nitrogen gas and seven different electric fields, so
      that relative standard deviations (RSD) could be assessed for each molecule and
      structural differences studied. The primary metabolites analyzed to date have
      come from key metabolism pathways such as glycolysis, the pentose phosphate
      pathway and the tricarboxylic acid cycle, while the secondary metabolites
      consisted of classes such as terpenes and flavonoids, and the xenobiotics
      represented a range of molecules from antibiotics to polycyclic aromatic
      hydrocarbons. Different CCS trends were observed for several of the diverse small
      molecule classes and when urine features were matched to the database, the
      addition of the IMS dimension greatly reduced the possible number of candidate
      molecules. This CCS database and structural information are freely available for
      download at http://panomics.pnnl.gov/metabolites/ with new molecules being added
      frequently.

PMID- 29568437
TI  - Mechanically induced pyrogallol[4]arene hexamer assembly in the solid state
      extends the scope of molecular encapsulation.
AB  - Pyrogallol[4]arene hexamers are hydrogen-bonded molecular capsules of exceptional
      kinetic stability that can entrap small molecule guests indefinitely, without
      exchange, at ambient temperatures. Here, we report on the use of a ball mill to
      induce self-assembly of the capsule components and the guests in the solid state.
      Stoichiometric amounts of pyrogallol[4]arene and a guest, which can be an arene,
      alkane, amine, or carboxylic acid, were milled at 30 Hz for fixed durations,
      dissolved, and characterization by NMR. Most of the resulting encapsulation
      complexes were kinetically stable but thermodynamically unstable in solution, and
      the yield of their formation correlates with the duration of the milling and is
      related to the structures of guest and host. This method extends the scope of
      molecular encapsulation, as demonstrated by the preparation of kinetically
      trapped encapsulation complexes of [2.2]paracyclophane, for which we could find
      no other method of preparation. To gain mechanistic insights into the solid-state
      assembly process, we characterized the milled powders using 13C CP-MAS NMR, we
      studied the effects of changing the alkane domain of the host, and we examined
      how dissolution conditions impact on the distribution of observed encapsulation
      complexes once in solution. The results support a mechanism comprising
      mechanically induced solid-state reorganization to produce a mixture rich in
      nearly or fully assembled guest-filled capsules.

PMID- 29568438
TI  - Template-directed self-assembly of dynamic covalent capsules with polar
      interiors.
AB  - Chiral polyimine molecular capsules with polar interiors have been prepared
      through template covalent dynamic self-assembly. An aryl-extended tetraaldehyde
      calix[4]pyrrole scaffold was condensed with suitable diamines as linkers using
      templates for efficient self-assembly. The capsular complexes were characterized
      in solution, gas phase and the solid-state. Unprecedented transfer of asymmetry
      was observed from a chiral diamine linker to the resulting supramolecular
      capsular assembly.

PMID- 29568439
TI  - Flexible inorganic light emitting diodes based on semiconductor nanowires.
AB  - The fabrication technologies and the performance of flexible nanowire light
      emitting diodes (LEDs) are reviewed. We first introduce the existing approaches
      for flexible LED fabrication, which are dominated by organic technologies, and we
      briefly discuss the increasing research effort on flexible inorganic LEDs
      achieved by micro-structuring and transfer of conventional thin films. Then,
      flexible nanowire-based LEDs are presented and two main fabrication technologies
      are discussed: direct growth on a flexible substrate and nanowire membrane
      formation and transfer. The performance of blue, green, white and bi-color
      flexible LEDs fabricated following the transfer approach is discussed in more
      detail.

PMID- 29568441
TI  - The significance of bromide in the Brust-Schiffrin synthesis of thiol protected
      gold nanoparticles.
AB  - The mechanism of the two-phase Brust-Schiffrin synthesis of alkane thiol
      protected metal nanoparticles is known to be highly sensitive to the precursor
      species and reactant conditions. In this work X-ray absorption spectroscopy is
      used in conjunction with liquid/liquid electrochemistry to highlight the
      significance of Br- in the reaction mechanism. The species [AuBr4]- is shown to
      be a preferable precursor in the Brust-Schiffrin method as it is more resistant
      to the formation of Au(i) thiolate species than [AuCl4]-. Previous literature has
      demonstrated that avoidance of the Au(i) thiolate is critical to achieving a good
      yield of nanoparticles, as [Au(i)X2]- species are more readily reduced by NaBH4.
      We propose that the observed behavior of [AuBr4]- species described herein
      explains the discrepancies in reported behavior present in the literature to
      date. This new mechanistic understanding should enable nanoparticle synthesis
      with a higher yield and reduce particle size polydispersity.

PMID- 29568440
TI  - Chemoenzymatic synthesis of heparan sulfate and heparin oligosaccharides and NMR
      analysis: paving the way to a diverse library for glycobiologists.
AB  - Heparan sulfate (HS) is a member of the glycosaminoglycans (GAG) family that
      plays essential roles in biological processes from animal sources. Heparin, a
      highly sulfated form of HS, is widely used as anticoagulant drug worldwide. The
      high diversity and complexity of HS and heparin represent a roadblock for
      structural characterization and biological activity studies. Access to
      structurally defined oligosaccharides is critical for the successful development
      of HS and heparin structure-activity relationships. In this study, a library of
      66 HS and heparin oligosaccharides covering different sulfation patterns and
      sizes was prepared through an efficient method of chemoenzymatic synthesis. A
      systematic nuclear magnetic resonance spectroscopy study was firstly undertaken
      for every oligosaccharide in the library. In addition to the availability of
      different oligosaccharides, this work also provides spectroscopic data helpful
      for characterizing more complicated polysaccharide structures providing a
      safeguard to ensure the quality of the drug heparin. This HS/heparin library will
      be useful for activity screening and facilitate future structure-activity
      relationship studies.

PMID- 29568442
TI  - Exploiting rhodium-catalysed ynamide hydroacylation as a platform for divergent
      heterocycle synthesis.
AB  - The first examples of ynamide hydroacylation are described. Using rhodium
      catalysis, linear beta-enaminone products are generated in high yield and
      excellent regioselectivity from the combination of aldehydes and ynamides. The
      enaminone products are subsequently used as a platform to construct a diverse
      array of substituted pyrazoles, pyrimidines, and isoxazoles in a two-step, one
      pot sequence. It was found that with judicious choice of catalyst system it was
      possible to overturn the regioselectivity of the hydroacylation reaction to
      generate alpha-enaminone products.

PMID- 29568443
TI  - A modular route to boron doped PAHs by combining borylative cyclisation and
      electrophilic C-H borylation.
AB  - Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach
      for modifying key physical properties, however, there are extremely few modular
      routes that enable facile formation of B-, B2- and B,N-(specifically not
      containing direct B-N bonds) doped PAHs despite the growing importance of these
      materials. Sequential, one pot borylative cyclisation/intramolecular
      electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to
      access novel B-, B,N- and B2-doped (PAHs). The initial products,
      dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with
      [Ph3C][BF4]/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However,
      for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior
      to Trip installation due to preferential oxidation of an isopropylaryl moiety to
      the styrene. This alternative sequence enables access to Trip-B-PAHs and to
      structurally constrained B and B2-PAHs. Analysis of the solid state structures
      and optoelectronic properties of these PAHs confirm that frontier orbital
      energies, extended packing structures, Stokes shift and quantum yields all can be
      rationally modified using this methodology. The simplicity of this synthetic
      approach makes it a powerful tool for rapidly generating novel bench stable boron
      doped PAHs, which is important for facilitating further structure-property
      relationship studies and the wider utilisation of these materials in
      optoelectronic applications.

PMID- 29568444
TI  - Thiosemicarbazone organocatalysis: tetrahydropyranylation and 2
      deoxygalactosylation reactions and kinetics-based mechanistic investigation.
AB  - The first use of thiosemicarbazone-based organocatalysis was demonstrated on both
      tetrahydropyranylation and 2-deoxygalactosylation reactions. The organocatalysts
      were optimised using kinetics-based selection. The best catalyst outperformed
      previously reported thiourea catalysts for tetrahydropyranylation by 50-fold.
      Hammett investigations of both the organocatalyst and the substrate indicate an
      oxyanion hole-like reaction mechanism.

PMID- 29568445
TI  - Efficient and stable single-doped white OLEDs using a palladium-based
      phosphorescent excimer.
AB  - A tetradentate Pd(ii) complex, Pd3O3, which exhibits highly efficient excimer
      emission is synthesized and characterized. Pd3O3 can achieve blue emission
      despite using phenyl-pyridine emissive ligands which have been a mainstay of
      stable green and red phosphorescent emitter designs, making Pd3O3 a good
      candidate for stable blue or white OLEDs. Pd3O3 exhibits strong and efficient
      phosphorescent excimer emission expanding the excimer based white OLEDs beyond
      the sole class of Pt complexes. Devices of Pd3O3 demonstrate peak external
      quantum efficiencies as high as 24.2% and power efficiencies of 67.9 Lm per W for
      warm white devices. Furthermore, Pd3O3 devices in a carefully designed stable
      structure achieved a device operational lifetime of nearly 3000 h at 1000 cd m-2
      without any outcoupling enhancement while simultaneously achieving peak external
      quantum efficiencies of 27.3% and power efficiencies over 81 Lm per W.

PMID- 29568446
TI  - De novo identification of lipid II binding lipopeptides with antibacterial
      activity against vancomycin-resistant bacteria.
AB  - Creative strategies for identifying new antibiotics are essential to addressing
      the looming threat of a post-antibiotic era. We here report the use of a targeted
      peptide phage display screen as a means of generating novel antimicrobial
      lipopeptides. Specifically, a library of phage displayed bicyclic peptides was
      screened against a biomolecular target based on the bacterial cell wall precursor
      lipid II. In doing so we identified unique lipid II binding peptides that upon
      lipidation were found to be active against a range of Gram-positive bacteria
      including clinically relevant strains of vancomycin resistant bacteria.
      Optimization of the peptide sequence led to variants with enhanced antibacterial
      activity and reduced hemolytic activity. Biochemical experiments further confirm
      a lipid II mediated mode of action for these new-to-nature antibacterial
      lipopeptides.

PMID- 29568447
TI  - Bond breakage under pressure in a metal organic framework.
AB  - The internal free volume of porous materials diminishes upon mechanical
      compression, and such volume collapse can have chemical consequences. We report
      here the endothermic bond breakage in a metal-organic framework (MOF) during
      compression-induced collapse. Upon bulk compression at 1.9 GPa, the effective
      number for Zr-O bonds between Zr(iv) ions and carboxylate groups in UiO-66
      decreased from 4.0 to 1.9, as determined by EXAFS, and the internal free volume
      was synchronously collapsed. Consistent with the EXAFS data, IR spectra confirmed
      conversion of syn-syn bridging carboxylates to monodentate ligation, thus
      establishing mechanochemical reactions induced by external compression of MOFs.
      Substantial mechanical energy (~4 kJ g-1) was absorbed by UiO-66 nanocrystals
      during compression, as demonstrated from nanocompression of single crystals (600
      nm) in situ during scanning electron microscopy, which establishes the potential
      application of MOFs as mechanical energy absorbers for hydrostatic and shock
      compression.

PMID- 29568448
TI  - An ultrasensitive fluorogenic probe for revealing the role of glutathione in
      chemotherapy resistance.
AB  - Unveiling the detailed roles of glutathione (GSH) in chemoresistance necessitates
      a reliable assay for its detection in intact live specimens. Herein, by taking
      advantage of the susceptibility of electron-poor Csp2 -Ssufinyl bond to GSH
      nucleophilic attack, we developed a naphthalimide-sulfoxide based fluorogenic
      probe (Na-8) applicable for tracking endogenous GSH fluctuation in live cells. Na
      8 features a high degree of sensitivity towards GSH as demonstrated by its utmost
      2200-fold fluorogenic response. As a proof of concept, Na-8 has been applied to
      image GSH in liver cancer HepG2 cells with the normal L02 cell counterparts
      serving as a control, and elevated GSH level was observed in HepG2 in contrast to
      L02. Further experiments showed that this elevated GSH level was involved in
      doxorubicin-resistance but not in cisplatin-resistance. Noteworthy, monitoring
      GSH change in HepG2 and L02 cells in response to doxorubicin treatment revealed
      that while normal cells showed a burst of GSH in adaption to doxorubicin
      treatment, no significant change was detected in HepG2 cells, suggesting that
      HepG2 cells have been preconditioned by their intrinsic oxidative stress which
      confers drug-resistance. Given the observed sensitivity and spatiotemporal
      resolution, Na-8 should hold promise for future study on the detailed roles of
      GSH in drug-resistance.

PMID- 29568449
TI  - Single-cell study of the extracellular matrix effect on cell growth by in situ
      imaging of gene expression.
AB  - Cell behaviors are known to be regulated by the cellular microenvironment.
      Traditional cell-population based analysis methods need to separate cells from
      their extracellular matrix (ECM) and cannot resolve the heterogeneity of cell
      behaviors. Herein, an in situ single-cell analysis method based on rolling circle
      amplification was exploited to image gene expression in single cells for
      investigating the effect of ECM stiffness on cell growth. This method enables the
      simultaneous quantifying of the cell phenotype and gene expression at the single
      cell level, which can help in understanding the underlying molecular mechanism of
      cell growth. It is found that ECM stiffness could affect cell growth via
      regulating the expression level of the cytoskeleton-assembly associated genes
      PFN1 and CFL1 and their co-expression pattern. Therefore, this single-cell
      analysis platform may facilitate us to tap into the study of "single-cell
      phenotypes" and elucidate the disease association of ECMs.

PMID- 29568450
TI  - Integration of intracellular telomerase monitoring by electrochemiluminescence
      technology and targeted cancer therapy by reactive oxygen species.
AB  - Cancer therapies based on reactive oxygen species (ROS) have emerged as promising
      clinical treatments. Electrochemiluminescence (ECL) technology has also attracted
      considerable attention in the field of clinical diagnosis. However, studies about
      the integration of ECL diagnosis and ROS cancer therapy are very rare. Here we
      introduce a novel strategy that employs ECL technology and ROS to fill the above
      vacancy. Briefly, an ITO electrode was electrodeposited with polyluminol-Pt NPs
      composite films and modified with aptamer DNA to capture HL-60 cancer cells with
      high specificity. After that, mesoporous silica nanoparticles (MSNs) filled with
      phorbol 12-myristate 13-acetate (PMA) were closed by the telomerase primer DNA (T
      primer DNA) and aptamer. After aptamer on MSN@PMA recognized and combined with
      the HL-60 cancer cells with high specificity, T-primer DNA on MSN@PMA could be
      moved away from the MSN@PMA surface after extension by telomerase in the HL-60
      cancer cells and PMA was released to induce the production of ROS by the HL-60
      cancer cells. After that, the polyluminol-Pt NPs composite films could react with
      hydrogen peroxide (a major ROS) and generate an ECL signal. Thus the
      intracellular telomerase activity of the HL-60 cancer cells could be detected in
      situ. Besides, ROS could induce apoptosis in the HL-60 cancer cells with high
      efficacy by causing oxidative damage to the lipids, protein, and DNA. Above all,
      the designed platform could not only detect intracellular telomerase activity
      instead of that of extracted telomerase, but could also kill targeted tumors by
      ECL technology and ROS.

PMID- 29568451
TI  - High-efficiency thermoelectric Ba8Cu14Ge6P26: bridging the gap between tetrel
      based and tetrel-free clathrates.
AB  - A new type-I clathrate, Ba8Cu14Ge6P26, was synthesized by solid-state methods as
      a polycrystalline powder and grown as a cm-sized single crystal via the vertical
      Bridgman method. Single-crystal and powder X-ray diffraction show that
      Ba8Cu14Ge6P26 crystallizes in the cubic space group Pm3n (no. 223). Ba8Cu14Ge6P26
      is the first representative of anionic clathrates whose framework is composed of
      three atom types of very different chemical natures: a transition metal, tetrel
      element, and pnicogen. Uniform distribution of the Cu, Ge, and P atoms over the
      framework sites and the absence of any superstructural or local ordering in
      Ba8Cu14Ge6P26 were confirmed by synchrotron X-ray diffraction, electron
      diffraction and high-angle annular dark field scanning transmission electron
      microscopy, and neutron and X-ray pair distribution function analyses.
      Characterization of the transport properties demonstrate that Ba8Cu14Ge6P26 is a
      p-type semiconductor with an intrinsically low thermal conductivity of 0.72 W m-1
      K-1 at 812 K. The thermoelectric figure of merit, ZT, for a slice of the Bridgman
      grown crystal of Ba8Cu14Ge6P26 approaches 0.63 at 812 K due to a high power
      factor of 5.62 MUW cm-1 K-2. The thermoelectric efficiency of Ba8Cu14Ge6P26 is on
      par with the best optimized p-type Ge-based clathrates and outperforms the
      majority of clathrates in the 700-850 K temperature region, including all tetrel
      free clathrates. Ba8Cu14Ge6P26 expands clathrate chemistry by bridging
      conventional tetrel-based and tetrel-free clathrates. Advanced transport
      properties, in combination with earth-abundant framework elements and congruent
      melting make Ba8Cu14Ge6P26 a strong candidate as a novel and efficient
      thermoelectric material.

PMID- 29568452
TI  - Transition metal redox switches for reversible "on/off" and "slow/fast" single
      molecule magnet behaviour in dysprosium and erbium bis-diamidoferrocene
      complexes.
AB  - Single-molecule magnets (SMMs) are considered viable candidates for next
      generation data storage and quantum computing. Systems featuring switchability of
      their magnetization dynamics are particularly interesting with respect to
      accessing more complex logic gates and device architectures. Here we show that
      transition metal based redox events can be exploited to enable reversible
      switchability of slow magnetic relaxation of magnetically anisotropic lanthanide
      ions. Specifically, we report anionic homoleptic bis-diamidoferrocene complexes
      of Dy3+ (oblate) and Er3+ (prolate) which can be reversibly oxidized by one
      electron to yield their respective charge neutral redox partners (Dy: [1]- , 1;
      Er: [2]- , 2). Importantly, compounds 1 and 2 are thermally stable which allowed
      for detailed studies of their magnetization dynamics. We show that the Dy3+[1]-
      /1 system can function as an "on"/"off" or a "slow"/"fast" redox switchable SMM
      system in the absence or presence of applied dc fields, respectively. The Er3+
      based [2]- /2 system features "on"/"off" switchability of SMM properties in the
      presence of applied fields. Results from electrochemical investigations, UV-vis
      NIR spectroscopy, and 57Fe Mossbauer spectroscopy indicate the presence of
      significant electronic communication between the mixed-valent Fe ions in 1 and 2
      in both solution and solid state. This comparative evaluation of redox-switchable
      magnetization dynamics in low coordinate lanthanide complexes may be used as a
      potential blueprint toward the development of future switchable magnetic
      materials.

PMID- 29568454
TI  - Identification of catabolite control protein A from Staphylococcus aureus as a
      target of silver ions.
AB  - Staphylococcus aureus is one of the most common pathogenic bacteria that causes
      human infectious diseases. The emergence of antibiotic-resistant strains of S.
      aureus promotes the development of new anti-bacterial strategies. Silver ions
      (Ag+) have attracted profound attention due to their broad-spectrum antimicrobial
      activities. Although the antibacterial properties of silver have been well known
      for many centuries, its mechanism of action remains unclear and its protein
      targets are rarely reported. Herein, we identify the catabolite control protein A
      (CcpA) of S. aureus as a putative target for Ag+. CcpA binds 2 molar equivalents
      of Ag+via its two cysteine residues (Cys216 and Cys242). Importantly, Ag+ binding
      induces CcpA oligomerization and abolishes its DNA binding capability, which
      further attenuates S. aureus growth and suppresses alpha-hemolysin toxicity. This
      study extends our understanding of the bactericidal effects of silver.

PMID- 29568453
TI  - A thiocyanopalladation/carbocyclization transformation identified through
      enzymatic screening: stereocontrolled tandem C-SCN and C-C bond formation.
AB  - Herein we describe a formal thiocyanopalladation/carbocyclization transformation
      and its parametrization and optimization using a new elevated temperature plate
      based version of our visual colorimetric enzymatic screening method for reaction
      discovery. The carbocyclization step leads to C-SCN bond formation in tandem with
      C-C bond construction and is highly stereoselective, showing nearly absolute 1,2
      anti-stereoinduction (5 examples) for substrates bearing allylic substitution,
      and nearly absolute 1,3-syn-stereoinduction (16 examples) for substrates bearing
      propargylic substitution. Based upon these high levels of stereoinduction, the
      dependence of the 1,2-stereoinduction upon cyclization substrate geometry, and
      the generally high preference for the transoid vinyl thiocyanate alkene geometry,
      a mechanistic model is proposed, involving (i) Pd(ii)-enyne coordination, (ii)
      thiocyanopalladation, (iii) migratory insertion and (iv) beta-elimination.
      Examples of transition metal-mediated C-SCN bond formation that proceed smoothly
      on unactivated substrates and allow for preservation of the SCN moiety are
      lacking. Yet, the thiocyanate functionality is of great value for biophysical
      chemistry (vibrational Stark effect) and medicinal chemistry (S,N-heterocycle
      construction). The title transformation accommodates C-, O-, N- and S-bridged
      substrates (6 examples), thereby providing the corresponding carbocyclic or
      heterocyclic scaffolds. The reaction is also shown to be compatible with a
      significant range of substituents, varying in steric and electronic demand,
      including a wide range of substituted aromatics, fused bicyclic and heterocyclic
      systems, and even biaryl systems. Combination of this new transformation with
      asymmetric allylation and Grubbs ring-closing metathesis provides for a
      streamlined enantio- and diastereoselective entry into the oxabicyclo[3.2.1]octyl
      core of the natural products massarilactone and annuionone A, as also evidenced
      by low temperature X-ray crystal structure determination. Utilizing this bicyclic
      scaffold, we demonstrate the versatility of the thiocyanate moiety for structural
      diversification post-cyclization. Thus, the bridging vinyl thiocyanate moiety is
      smoothly elaborated into a range of derivative functionalities utilizing
      transformations that cleave the S-CN bond, add the elements of RS-CN across a pi
      system and exploit the SCN moiety as a cycloaddition partner (7 diverse
      examples). Among the new functionalities thereby generated are thiotetrazole and
      sulfonyl tetrazole heterocycles that serve as carboxylate and phosphate
      surrogates, respectively, highlighting the potential of this approach for future
      applications in medicinal chemistry or chemical biology.

PMID- 29568455
TI  - Precise synthesis of unique polydopamine/mesoporous calcium phosphate hollow
      Janus nanoparticles for imaging-guided chemo-photothermal synergistic therapy.
AB  - Multifunctional polymer-inorganic Janus nanoparticles (JNPs) that simultaneously
      have therapeutic and imaging functions are highly desired in biomedical
      applications. Here, we fabricated spherical polydopamine/mesoporous calcium
      phosphate hollow JNPs (PDA/mCaP H-JNPs) via a novel and facile approach. The
      obtained PDA/mCaP H-JNPs were further selectively functionalized with indocyanine
      green (ICG) and methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to
      achieve a superior photoacoustic (PA) imaging capability and stability, while the
      other mCaP sides with hollow cavities served as storage spaces and passages for
      the anti-cancer drug, doxorubicin (DOX). The resultant PEG-ICG-PDA/mCaP H-JNPs
      possess excellent biocompatibility, a competent drug loading capability, high
      photothermal conversion efficiency, strong near-infrared (NIR) absorbance, and
      pH/NIR dual-responsive properties, enabling the H-JNPs to be applied for PA
      imaging-guided synergistic cancer chemo-phototherapy in vitro and in vivo.
      Furthermore, the synthetic approach could be extended to prepare PDA/various
      mesoporous inorganic H-JNPs with spherical shapes for specific applications.

PMID- 29568456
TI  - Bis(aminothiolato)nickel nanosheet as a redox switch for conductivity and an
      electrocatalyst for the hydrogen evolution reaction.
AB  - A pi-conjugated coordination nanosheet comprising bis(aminothiolato)nickel (NiAT)
      moieties was synthesized by the reaction of Ni(acac)2 with 1,3,5-triaminobenzene
      2,4,6-trithiol at liquid-liquid and gas-liquid interfaces. The sheet thickness
      could be controlled down to a single layer (0.6 nm). Selected area electron
      diffraction and grazing incidence X-ray diffraction analyses indicated the
      formation of a flat crystalline sheet with a kagome lattice stacked in a
      staggered alignment. NiAT was reversibly interconverted to a
      bis(iminothiolato)nickel (NiIT) nanosheet by the chemical 2H+-2e- reaction, which
      was accompanied by a drastic change in electrical conductivity from 3 * 10-6 to 1
      * 10-1 S cm-1. This change in conductivity was explained by the difference in
      band structures between NiAT and NiIT. NiAT acted as an efficient electrocatalyst
      for the hydrogen evolution reaction, showing strong acid durability and an onset
      overpotential of -0.15 V.

PMID- 29568457
TI  - Enantioselective synthesis of cyclopenta[b]benzofurans via an organocatalytic
      intramolecular double cyclization.
AB  - An enantioselective organocatalytic strategy, combining Bronsted base and N
      heterocyclic carbene catalysis in a unique manner, is demonstrated for a concise
      construction of the privileged cyclopenta[b]benzofuran scaffold, present in many
      bioactive compounds having both academic and commercial interests. The reaction
      concept relies on an intramolecular one-pot double cyclization involving a cycle
      specific enantioselective Michael addition followed by a benzoin condensation of
      ortho-substituted cinnamaldehydes. Cyclopenta[b]benzofurans were achieved in
      moderate to good yields, with excellent stereoselectivities. A proof of principle
      for a diastereodivergent variation is demonstrated through the synthesis of
      cyclopenta[b]benzofurans containing two contiguous aromatic substituents in a
      substitution pattern present in commercial and natural compounds. Furthermore,
      several transformations have been performed, demonstrating the synthetic utility
      of the products. Finally, insights into the activation mode and stereoindution
      models are presented for this new synthetic strategy.

PMID- 29568458
TI  - Ex situ generation of stoichiometric HCN and its application in the Pd-catalysed
      cyanation of aryl bromides: evidence for a transmetallation step between two
      oxidative addition Pd-complexes.
AB  - A protocol for the Pd-catalysed cyanation of aryl bromides using near
      stoichiometric and gaseous hydrogen cyanide is reported for the first time. A two
      chamber reactor was adopted for the safe liberation of ex situ generated HCN in a
      closed environment, which proved highly efficient in the Ni-catalysed
      hydrocyanation as the test reaction. Subsequently, this setup was exploited for
      converting a range of aryl and heteroaryl bromides (28 examples) directly into
      the corresponding benzonitriles in high yields, without the need for cyanide
      salts. Cyanation was achieved employing the Pd(0) precatalyst, P(tBu)3-Pd-G3 and
      a weak base, potassium acetate, in a dioxane-water solvent mixture. The
      methodology was also suitable for the synthesis of 13C-labelled benzonitriles
      with ex situ generated 13C-hydrogen cyanide. Stoichiometric studies with the
      metal complexes were undertaken to delineate the mechanism for this catalytic
      transformation. Treatment of Pd(P(tBu)3)2 with H13CN in THF provided two Pd
      hydride complexes, (P(tBu)3)2Pd(H)(13CN), and [(P(tBu)3)Pd(H)]2Pd(13CN)4, both of
      which were isolated and characterised by NMR spectroscopy and X-ray crystal
      structure analysis. When the same reaction was performed in a THF : water mixture
      in the presence of KOAc, only (P(tBu)3)2Pd(H)(13CN) was formed. Subjection of
      this cyano hydride metal complex with the oxidative addition complex
      (P(tBu)3)Pd(Ph)(Br) in a 1 : 1 ratio in THF led to a transmetallation step with
      the formation of (P(tBu)3)2Pd(H)(Br) and 13C-benzonitrile from a reductive
      elimination step. These experiments suggest the possibility of a catalytic cycle
      involving initially the formation of two Pd(ii)-species from the oxidative
      addition of L n Pd(0) into HCN and an aryl bromide followed by a transmetallation
      step to L n Pd(Ar)(CN) and L n Pd(H)(Br), which both reductively eliminate, the
      latter in the presence of KOAc, to generate the benzonitrile and L n Pd(0).

PMID- 29568459
TI  - Oligomers of cyclopentadithiophene-vinylene in aromatic and quinoidal versions
      and redox species with intermediate forms.
AB  - A new series of pi-conjugated oligomers based on the 4,4 dihexyl-4H
      cyclopenta[2,1-b:3,4-b']dithiophene vinylene repeating unit has been prepared and
      characterized by X-ray, electrochemical, spectroscopic (UV-Vis absorption,
      emission and Raman) and density functional theory methods. The oligomers in their
      neutral, oxidized and reduced forms have been investigated. The neutral compounds
      show a longer mean conjugation length than oligothiophenes and oligothiophene
      vinylenes and display very rich redox chemistry with the stabilization of
      polycationic states of which the radical cations and dications are strong NIR
      absorbers, the latter displaying singlet diradicaloid character. An interesting
      complementarity between the sequence of aromatic-quinoidal structural segments in
      the radical cations and dications has been described and interpreted. Two
      derivatives with the 4,4 dihexyl-4H-cyclopenta[2,1-b:3,4-b']dithiophene vinylene
      unit, disubstituted either with electron donor, bis(triaryl amino) groups, or
      acceptors bis(dicyano-methylene) caps enforcing a quinoidal structure in the
      dithiophene-vinylene bridge, have been also synthesized and characterized. The
      radical cation of the triarylamine compound and the radical anion of the
      tetracyano compound similarly display hole and electron charge localization, or
      confinement, in the nitrogen and dicyano surrounding parts, or class II mixed
      valence systems, while their dication and dianion species, conversely, are open
      shell diradical (i.e., polaron pair) and closed-shell (i.e., bipolaron),
      respectively. The preparation of these new pi-conjugated oligomers gives way to
      the realization of compounds with new electronic properties and unique structures
      potentially exploitable in organic electronics.

PMID- 29568460
TI  - HOMO inversion as a strategy for improving the light-absorption properties of
      Fe(ii) chromophores.
AB  - A computational study of a series of [Fe(tpy)2]2+ (tpy = 2,2':6',2''-terpyridine)
      complexes is reported, where the tpy ligand is substituted at the 4, 4', and 4''
      positions by electron donor (furan, thiophene, selenophene, NH2) and acceptor
      (carboxylic acid, NO2) groups. Using DFT and TD-DFT calculations, we show that
      the substitution of heterocyclic pi donor groups onto the tpy ligand scaffold
      leads to marked improvement of the [Fe(tpy)2]2+ absorption properties,
      characterized by increased molar extinction coefficients, shift of absorption
      energies to longer wavelengths, and broadening of the absorption spectrum in the
      visible region. The observed changes in the light absorption properties are due
      to destabilization of ligand-centered occupied pi orbital energies, thus
      increasing the interactions between the metal t2g (HOMO) and ligand pi orbitals.
      Substitution of extended pi-conjugated groups, such as thienothiophene and
      dithienothiophene, further destabilizes the ligand pi orbital energies, resulting
      in a fully ligand-localized HOMO (i.e., HOMO inversion) and additional
      improvement of the light absorption properties. These results open up a new
      strategy to tuning the light absorption properties of Fe(ii)-polypyridines.

PMID- 29568461
TI  - Influence of the [4Fe-4S] cluster coordinating cysteines on active site
      maturation and catalytic properties of C. reinhardtii [FeFe]-hydrogenase.
AB  - [FeFe]-Hydrogenases catalyze the evolution and oxidation of hydrogen using a
      characteristic cofactor, termed the H-cluster. This comprises an all cysteine
      coordinated [4Fe-4S] cluster and a unique [2Fe] moiety, coupled together via a
      single cysteine. The coordination of the [4Fe-4S] cluster in HydA1 from
      Chlamydomonas reinhardtii was altered by single exchange of each cysteine (C115,
      C170, C362, and C366) with alanine, aspartate, or serine using site-directed
      mutagenesis. In contrast to cysteine 115, the other three cysteines were found to
      be dispensable for stable [4Fe-4S] cluster incorporation based on iron
      determination, UV/vis spectroscopy and electron paramagnetic resonance. However,
      the presence of a preformed [4Fe-4S] cluster alone does not guarantee stable
      incorporation of the [2Fe] cluster. Only variants C170D, C170S, C362D, and C362S
      showed characteristic signals for an inserted [2Fe] cluster in Fourier-transform
      infrared spectroscopy. Hydrogen evolution and oxidation were observed for these
      variants in solution based assays and protein-film electrochemistry. Catalytic
      activity was lowered for all variants and the ability to operate in either
      direction was also influenced.

PMID- 29568462
TI  - Simple organic structure directing agents for synthesizing nanocrystalline
      zeolites.
AB  - The synthesis of the ZSM-5 and beta zeolites in their nanosized form has been
      achieved by using simple alkyl-substituted mono-cationic cyclic ammonium cations
      as OSDA molecules. The particular combination of a cyclic fragment and a short
      linear alkyl-chain group (preferentially C4) within the monocationic OSDA
      molecules allows directing the crystallization of nanosized zeolites with
      excellent solid yields (above 90%). Interestingly, the formation of the nanosized
      ZSM-5 and beta zeolites mostly depends on the size and nature of the cyclic
      fragment of the OSDA molecule, resulting in all cases in nanocrystalline solids
      with homogeneous distributions of particle sizes (~10-25 nm) and controlled Si/Al
      molar ratios (~15-30). The achieved nanosized ZSM-5 and beta zeolites have been
      extensively characterized by different techniques to study their physico-chemical
      properties, such as chemical composition, pore accessibility or Bronsted acidity,
      among others. Moreover, the catalytic properties of the nanosized ZSM-5 and beta
      zeolites have been evaluated for different chemical reactions, including methanol
      to-olefins (MTO) in the case of ZSM-5, and alkylation of benzene with propylene
      to obtain cumene and oligomerization of light olefins to liquid fuels in the case
      of beta, observing in all cases improved catalytic activity and product
      selectivity towards target products when compared to related catalysts.

PMID- 29568463
TI  - Catalysis with chalcogen bonds: neutral benzodiselenazole scaffolds with high
      precision selenium donors of variable strength.
AB  - The benzodiselenazoles (BDS) introduced in this report fulfill, for the first
      time, all the prerequisites for non-covalent high-precision chalcogen-bonding
      catalysis in the focal point of conformationally immobilized sigma holes on
      strong selenium donors in a neutral scaffold. Rational bite-angle adjustment to
      the long Se-C bonds was the key for BDS design. For the unprecedented BDS motif,
      synthesis of 12 analogs from o-xylene, crystal structure, sigma hole variation
      strategies, optoelectronic properties, theoretical and experimental anion binding
      as well as catalytic activity are reported. Chloride binding increases with the
      depth of the sigma holes down to KD = 11 MUM in THF. Catalytic activities follow
      the same trend and culminate in rate enhancements for transfer hydrogenation of
      quinolines beyond 100 000.

PMID- 29568464
TI  - Evolved polymerases facilitate selection of fully 2'-OMe-modified aptamers.
AB  - RNA or DNA aptamers with 2'-OMe-modifications have been pursued to increase
      resistance to nucleases, but have been difficult to identify because the OMe
      groups ablate polymerase recognition. We recently reported evolution of the
      thermostable DNA polymerases SFM4-6 and SFM4-9, which enable the efficient
      "transcription" and "reverse transcription", respectively, of 2'-OMe
      oligonucleotides. With these polymerases, we now report the first selection of
      fully 2'-OMe modified aptamers, specifically aptamers that bind human neutrophil
      elastase (HNE). Two aptamers, 2mHNE-1 and 2mHNE-2, were isolated after five
      rounds of selection, and four more, 2mHNE-3-6, after an additional five rounds
      that included selection pressure for binding in the presence of serum. All six
      aptamers bind with reasonable affinity, which requires the 2'-OMe substituents.
      Further characterization of one aptamer, 2mHNE-5, showed that unlike a previously
      reported natural anti-HNE aptamer, affinity for HNE is retained in the presence
      of high concentrations of salt or serum. The polymerases SFM4-6 and SFM4-9 should
      prove valuable for the production and further exploration of modified aptamers.

PMID- 29568465
TI  - Teixobactin analogues reveal enduracididine to be non-essential for highly potent
      antibacterial activity and lipid II binding.
AB  - Teixobactin is a highly promising antibacterial depsipeptide consisting of four d
      amino acids and a rare l-allo-enduracididine amino acid. l-allo-Enduracididine is
      reported to be important for the highly potent antibacterial activity of
      teixobactin. However, it is also a key limiting factor in the development of
      potent teixobactin analogues due to several synthetic challenges such as it is
      not commercially available, requires a multistep synthesis, long and repetitive
      couplings (16-30 hours). Due to all these challenges, the total synthesis of
      teixobactin is laborious and low yielding (3.3%). In this work, we have
      identified a unique design and developed a rapid synthesis (10 min MUwave
      assisted coupling per amino acid, 30 min cyclisation) of several highly potent
      analogues of teixobactin with yields of 10-24% by replacing the l-allo
      enduracididine with commercially available non-polar residues such as leucine and
      isoleucine. Most importantly, the Leu10-teixobactin and Ile10-teixobactin
      analogues have shown highly potent antibacterial activity against a broader panel
      of MRSA and Enterococcus faecalis (VRE). Furthermore, these synthetic analogues
      displayed identical antibacterial activity to natural teixobactin (MIC 0.25 MUg
      mL-1) against MRSA ATCC 33591 despite their simpler design and ease of synthesis.
      We have confirmed lipid II binding and measured the binding affinities of
      individual amino acid residues of Ala10-teixobactin towards geranyl pyrophosphate
      by NMR to understand the nature and strength of binding interactions. Contrary to
      current understanding, we have shown that a cationic amino acid at position 10 is
      not essential for target (lipid II) binding and potent antibacterial activity of
      teixobactin. We thus provide strong evidence contrary to the many assumptions
      made about the mechanism of action of this exciting new antibiotic. Introduction
      of a non-cationic residue at position 10 allows for tremendous diversification in
      the design and synthesis of highly potent teixobactin analogues and lays the
      foundations for the development of teixobactin analogues as new drug-like
      molecules to target MRSA and Mycobacterium tuberculosis.

PMID- 29568466
TI  - Ruthenium(ii)-catalyzed olefination via carbonyl reductive cross-coupling.
AB  - Natural availability of carbonyl groups offers reductive carbonyl coupling
      tremendous synthetic potential for efficient olefin synthesis, yet the catalytic
      carbonyl cross-coupling remains largely elusive. We report herein such a
      reaction, mediated by hydrazine under ruthenium(ii) catalysis. This method
      enables facile and selective cross-couplings of two unsymmetrical carbonyl
      compounds in either an intermolecular or intramolecular fashion. Moreover, this
      chemistry accommodates a variety of substrates, proceeds under mild reaction
      conditions with good functional group tolerance, and generates stoichiometric
      benign byproducts. Importantly, the coexistence of KO t Bu and bidentate
      phosphine dmpe is vital to this transformation.

PMID- 29568467
TI  - The alpha-tertiary amine motif drives remarkable selectivity for Pd-catalyzed
      carbonylation of beta-methylene C-H bonds.
AB  - The selective C-H carbonylation of methylene bonds in the presence of
      traditionally more reactive methyl C-H and C(sp2)-H bonds in alpha-tertiary
      amines is reported. The exceptional selectivity is driven by the bulky alpha
      tertiary amine motif, which we hypothesise orientates the activating C-H bond
      proximal to Pd in order to avoid an unfavourable steric clash with a second alpha
      tertiary amine on the Pd centre, promoting preferential cyclopalladation at the
      methylene position. The reaction tolerates a range of structurally interesting
      and synthetically versatile functional groups, delivering the corresponding beta
      lactam products in good to excellent yields.

PMID- 29568468
TI  - Site-isolated manganese carbonyl on bipyridine-functionalities of periodic
      mesoporous organosilicas: efficient CO2 photoreduction and detection of key
      reaction intermediates.
AB  - Well-defined and fully characterized supported CO2 reduction catalysts are
      developed through the immobilization of an earth abundant Mn complex on bpy-PMO
      (bpy = bipyridine; PMO = Periodic Mesoporous Organosilica) platform materials.
      The resulting isolated Mn-carbonyl centers coordinated to bipyridine
      functionalities of bpy-PMO catalyze the photoreduction of CO2 into CO and HCOOH
      with up to ca. 720 TON in the presence of BIH (1,3-dimethyl-2-phenyl-2,3-dihydro
      1H-benzoimidazole), used as the electron donor. A broad range of photochemical
      conditions (varying solvents, sacrificial electron donors, photosensitizer type
      and concentration, catalyst loading as well as the Mn loading within the PMO) are
      investigated, demonstrating high activity even for simple organic dyes and Zn
      porphyrin as photosensitizers. Spectroscopic and catalytic data also indicate
      that site isolation of the Mn complex in the PMO framework probably inhibits
      bimolecular processes such as dimerisation and disproportionation and thus allows
      the spectroscopic observation of key reaction intermediates, namely the two
      meridional isomers of the carbonyl complexes and the bipyridine radical anion
      species.

PMID- 29568469
TI  - Supramolecular assembly affording a ratiometric two-photon fluorescent nanoprobe
      for quantitative detection and bioimaging.
AB  - Fluorescence quantitative analyses for vital biomolecules are in great demand in
      biomedical science owing to their unique detection advantages with rapid,
      sensitive, non-damaging and specific identification. However, available
      fluorescence strategies for quantitative detection are usually hard to design and
      achieve. Inspired by supramolecular chemistry, a two-photon-excited fluorescent
      supramolecular nanoplatform (TPSNP) was designed for quantitative analysis with
      three parts: host molecules (beta-CD polymers), a guest fluorophore of sensing
      probes (Np-Ad) and a guest internal reference (NpRh-Ad). In this strategy, the
      TPSNP possesses the merits of (i) improved water-solubility and biocompatibility;
      (ii) increased tissue penetration depth for bioimaging by two-photon excitation;
      (iii) quantitative and tunable assembly of functional guest molecules to obtain
      optimized detection conditions; (iv) a common approach to avoid the limitation of
      complicated design by adjustment of sensing probes; and (v) accurate quantitative
      analysis by virtue of reference molecules. As a proof-of-concept, we utilized the
      two-photon fluorescent probe NHS-Ad-based TPSNP-1 to realize accurate
      quantitative analysis of hydrogen sulfide (H2S), with high sensitivity and good
      selectivity in live cells, deep tissues and ex vivo-dissected organs, suggesting
      that the TPSNP is an ideal quantitative indicator for clinical samples. What's
      more, TPSNP will pave the way for designing and preparing advanced supramolecular
      sensors for biosensing and biomedicine.

PMID- 29568470
TI  - Catalytic 1,2-dihydronaphthalene and E-aryl-diene synthesis via CoIII-Carbene
      radical and o-quinodimethane intermediates.
AB  - Catalytic synthesis of substituted 1,2-dihydronaphthalenes via metalloradical
      activation of o-styryl N-tosyl hydrazones ((E)-2-(prop-1-en-1-yl)benzene-N-tosyl
      hydrazones) is presented, taking advantage of the intrinsic reactivity of a
      cobalt(iii)-carbene radical intermediate. The method has been successfully
      applied to a broad range of substrates with various R1 substituents at the
      aromatic ring, producing the desired ring products in good to excellent isolated
      yields for substrates with an R2 = COOEt substituent at the vinylic position (~70
      90%). Changing the R2 moiety from an ester to other substituents has a
      surprisingly large influence on the (isolated) yields. This behaviour is
      unexpected for a radical rebound ring-closure mechanism, and points to a
      mechanism proceeding via ortho-quinodimethane (o-QDM) intermediates. Furthermore,
      substrates with an alkyl substituent on the allylic position reacted to form E
      aryl-dienes in excellent yields, rather than the expected 1,2
      dihydronaphthalenes. This result, combined with the outcome of supporting DFT
      calculations, strongly points to the release of reactive o-QDM intermediates from
      the metal centre in all cases, which either undergo a 6pi-cyclisation step to
      form the 1,2-dihydronaphthalenes, or a [1,7]-hydride shift to produce the E-aryl
      dienes. Trapping experiments using TEMPO confirm the involvement of cobalt(iii)
      carbene radical intermediates. EPR spectroscopic spin-trapping experiments using
      phenyl N-tert-butylnitrone (PBN) confirm the radical nature of the catalytic
      reaction.

PMID- 29568471
TI  - Effective stabilization of a planar phosphorus(iii) center embedded in a
      porphyrin-based fused aromatic skeleton.
AB  - Organophosphorus(iii) compounds usually take on stable pyramidal structures with
      a large inversion barrier of 30-35 kcal mol-1. In contrast, diphenylphosphine
      fused Ni(ii) porphyrin, where the phosphorus atom is directly attached at the
      meso-position and embedded in a rigid skeleton, exhibits a considerably
      planarized phosphorus center. Here we report the synthesis of a mesityl
      substituted Ni(ii) porphyrin analogue, 6, which allowed an evaluation of the
      inversion barrier (DeltaG?203) by variable temperature 1H NMR spectroscopy which
      showed it to be exceptionally small, at 14.0 kcal mol-1. The observed small
      inversion barrier has been attributed to conformational constraint imposed by the
      fused structure. In addition, it was thought that the planar transition state is
      stabilized by the Ni(ii) porphyrin network that allows the contribution of a 22pi
      aromatic circuit involving phosphorus lone-pair electrons. Along this postulate,
      we attempted to engineer diarylphosphine-fused porphyrins with smaller inversion
      barriers by replacing the fused benzene rings with five-membered heterocyclic
      rings such as thiophene, benzothiophene, benzofuran, indole, benzothiophene 1,1
      dioxide, and thiophene 1,1-dioxide. In that order, the aromatic character of the
      heterocycle decreases, which leads to increasing contribution of the 22pi
      aromatic circuit. Actually, the inversion barrier of the phosphorus center
      becomes smaller in this order and reaches 8.7 kcal mol-1 for thiophene 1,1
      dioxide-fused Ni(ii) porphyrin 15, supporting the postulate.

PMID- 29568472
TI  - Biomimetic inorganic camouflage circumvents antibody-dependent enhancement of
      infection.
AB  - Pre-existing antibodies can aggravate disease during subsequent infection or
      vaccination via the mechanism of antibody-dependent enhancement (ADE) of
      infection. Herein, using dengue virus (DENV) as a model, we present a versatile
      surface-camouflage strategy to obtain a virus core-calcium phosphate shell hybrid
      by self-templated biomineralization. The shelled DENV stealthily avoids
      recognition by pre-existing antibodies under extracellular conditions, resulting
      in the efficient abrogation of the ADE of infection both in vitro and in vivo.
      Moreover, the nanoshell can spontaneously degrade under intracellular conditions
      to restore the virus activity and immunogenicity due to its pH-sensitive
      behaviour. This work demonstrates that the biomimetic material shell can
      significantly improve the administration safety and potency of the DENV vaccine,
      which provides the promising prospect of chemically designed virus-material
      hybrids for immune evasion.

PMID- 29568473
TI  - Amyloid beta-peptides 1-40 and 1-42 form oligomers with mixed beta-sheets.
AB  - Two main amyloid-beta peptides of different length (Abeta40 and Abeta42) are
      involved in Alzheimer's disease. Their relative abundance is decisive for the
      severity of the disease and mixed oligomers may contribute to the toxic species.
      However, little is know about the extent of mixing. To study whether Abeta40 and
      Abeta42 co-aggregate, we used Fourier transform infrared spectroscopy in
      combination with 13C-labeling and spectrum calculation and focused on the amide I
      vibration, which is sensitive to backbone structure. Mixtures of monomeric
      labeled Abeta40 and unlabeled Abeta42 (and vice versa) were co-incubated for ~20
      min and their infrared spectrum recorded. The position of the main 13C-amide I'
      band shifted to higher wavenumbers with increasing admixture of 12C-peptide due
      to the presence of 12C-amides in the vicinity of 13C-amides. The results indicate
      that Abeta40 and Abeta42 form mixed oligomers with a largely random distribution
      of Abeta40 and Abeta42 strands in their beta-sheets. The structures of the mixed
      oligomers are intermediate between those of the pure oligomers. There is no
      indication that one of the peptides forces the backbone structure of its
      oligomers on the other peptide when they are mixed as monomers. We also
      demonstrate that isotope-edited infrared spectroscopy can distinguish aggregation
      modulators that integrate into the backbone structure of their interaction
      partner from those that do not. As an example for the latter case, the pro
      inflammatory calcium binding protein S100A9 is shown not to incorporate into the
      beta-sheets of Abeta42.

PMID- 29568474
TI  - Copper-catalyzed aminoalkynylation of alkenes with hypervalent iodine reagents.
AB  - A copper-catalyzed aminoalkynylation of alkenes is achieved with
      ethynylbenziodoxolone (EBX) reagents under mild conditions with only 1 mol%
      copper catalyst. This transformation allows for rapid construction of diverse
      important azahetereocycles and installation of valuable alkyne groups in one
      step. The developed method features remarkable substrate scope for both terminal
      and internal alkenes as well as different alkynyl groups, presenting great
      potential for broad applications in synthesis, bioconjugation, and molecular
      imaging.

PMID- 29568475
TI  - Mitochondria-targeted spin-labelled luminescent iridium anticancer complexes.
AB  - Mitochondria generate energy but malfunction in many cancer cells, hence
      targeting mitochondrial metabolism is a promising approach for cancer therapy.
      Here we have designed cyclometallated iridium(iii) complexes, containing one
      TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43H43N6O2Ir1.PF6] (Ir
      TEMPO1) and two TEMPO spin labels [C52H58N8O4Ir1.PF6] (Ir-TEMPO2). Electron
      paramagnetic resonance (EPR) spectroscopy revealed spin-spin interactions between
      the TEMPO units in Ir-TEMPO2. Both Ir-TEMPO1 and Ir-TEMPO2 showed bright
      luminescence with long lifetimes (ca. 35-160 ns); while Ir-TEMPO1 displayed
      monoexponential decay kinetics, the biexponential decays measured for Ir-TEMPO2
      indicated the presence of more than one energetically-accessible conformation.
      This observation was further supported by density functional theory (DFT)
      calculations. The antiproliferative activity of Ir-TEMPO2 towards a range of
      cancer cells was much greater than that of Ir-TEMPO1, and also the antioxidant
      activity of Ir-TEMPO2 is much higher against A2780 ovarian cancer cells when
      compared with Ir-TEMPO1. Most notably Ir-TEMPO2 was particularly potent towards
      PC3 human prostate cancer cells (IC50 = 0.53 MUM), being ca. 8* more active than
      the clinical drug cisplatin, and ca. 15* more selective towards cancer cells
      versus normal cells. Confocal microscopy showed that both Ir-TEMPO1 and Ir-TEMPO2
      localise in the mitochondria of cancer cells.

PMID- 29568476
TI  - Manipulating energy transfer in lanthanide-doped single nanoparticles for highly
      enhanced upconverting luminescence.
AB  - Energy transfer (ET) is of fundamental importance in tuning the optical
      performance of lanthanide-doped upconversion nanoparticles (UCNPs). However, the
      fine control and manipulation of the ETs particularly for deleterious cross
      relaxation type ETs (CR-ETs) in lanthanide-doped UCNPs remains a formidable
      challenge to date. Herein, we demonstrate a rational design strategy to
      manipulate the deleterious CR-ETs in lanthanide-doped UCNPs, by fine-tuning the
      distances at an extremely large length scale (>20 nm) among multiple lanthanide
      dopants that are simultaneously embedded into one single nanoparticle with
      specially designed multilayer nanostructures. The successful inhibition of the CR
      ETs leads to a significantly enhanced upconversion luminescence signal with an
      intensity ~70 times higher than that of co-doped conventional UCNPs. This finding
      paves a new way for the better control of the ETs in lanthanide-doped
      nanoparticles, and offers the possibility of constructing a series of promising
      single-nanocrystal-based anti-counterfeiting barcodes with well-identified UC
      emission color and lifetime outputs.

PMID- 29568477
TI  - MD simulations and QM/MM calculations show that single-site mutations of
      cytochrome P450BM3 alter the active site's complexity and the chemoselectivity of
      oxidation without changing the active species.
AB  - It is a long-standing mechanistic consensus that the mutation of the proton
      shuttle mediator Threonine (T) in Cytochrome P450 enzymes severs the water
      channel and thereby quenches the formation of the active species: the high-valent
      iron(iv)-oxo porphyrin pi-cation radical species, compound I (Cpd I). Using MD
      simulations and hybrid QM/MM calculations of P450BM3 we demonstrate that this is
      not the case. Thus, while the original water channel is disrupted in the T268A
      mutant of the enzyme, a new channel is formed that generates Cpd I. With this new
      understanding, we address the puzzling regiochemical and kinetic-isotope effect
      (KIE) results (Volz et al., J. Am. Chem. Soc., 2002, 124, 9724-9725) on the
      sulfoxidation and N-dealkylation of dimethyl-(4-methylsulfanyl-phenyl)-amine by
      wild type (WT) P450BM3 and its T268A vs. F87A mutants. We show that the observed
      variable ratio of S/Me oxidation for these enzymes, vis-a-vis the constant KIE,
      originates from Cpd I being the sole oxidant. Thus, while the conserved KIE
      probes the conserved nature of the transition state, the variable regiochemical
      S/Me ratio reflects the active-site reorganization in the mutants: the shifted
      location of the new water channel in T268A tightens the binding of the S-end by
      Cpd I and increases the S/Me ratio, whereas the absence of pi-interaction with
      the S-end in F87A creates a looser binding that lowers the S/Me ratio. Our
      results match the experimental findings. As such, this study sheds light on
      puzzling experimental results, and may shift a central paradigm in P450 research.
      The broader implication on enzymatic research is that a single-site mutation is
      not a localised alteration but one that may lead to a profound change in the
      active site, sufficiently so as to change the chemoselectivity of catalyzed
      reactions.

PMID- 29568478
TI  - Toward a patient-specific tissue engineered vascular graft.
AB  - Integrating three-dimensional printing with the creation of tissue-engineered
      vascular grafts could provide a readily available, patient-specific, autologous
      tissue source that could significantly improve outcomes in newborns with
      congenital heart disease. Here, we present the recent case of a candidate for our
      tissue-engineered vascular graft clinical trial deemed ineligible due to complex
      anatomical requirements and consider the application of three-dimensional
      printing technologies for a patient-specific graft. We 3D-printed a closed
      disposable seeding device and validated that it performed equivalently to the
      traditional open seeding technique using ovine bone marrow-derived mononuclear
      cells. Next, our candidate's preoperative imaging was reviewed to propose a
      patient-specific graft. A seeding apparatus was then designed to accommodate the
      custom graft and 3D-printed on a commodity fused deposition modeler. This
      exploratory feasibility study represents an important proof of concept advancing
      progress toward a rationally designed patient-specific tissue-engineered vascular
      graft for clinical application.

PMID- 29568479
TI  - Embryonic lethality is not sufficient to explain hourglass-like conservation of
      vertebrate embryos.
AB  - Background: Understanding the general trends in developmental changes during
      animal evolution, which are often associated with morphological diversification,
      has long been a central issue in evolutionary developmental biology. Recent
      comparative transcriptomic studies revealed that gene expression profiles of mid
      embryonic period tend to be more evolutionarily conserved than those in earlier
      or later periods. While the hourglass-like divergence of developmental processes
      has been demonstrated in a variety of animal groups such as vertebrates,
      arthropods, and nematodes, the exact mechanism leading to this mid-embryonic
      conservation remains to be clarified. One possibility is that the mid-embryonic
      period (pharyngula period in vertebrates) is highly prone to embryonic lethality,
      and the resulting negative selections lead to evolutionary conservation of this
      phase. Here, we tested this "mid-embryonic lethality hypothesis" by measuring the
      rate of lethal phenotypes of three different species of vertebrate embryos
      subjected to two kinds of perturbations: transient perturbations and genetic
      mutations. Results: By subjecting zebrafish (Danio rerio), African clawed frog
      (Xenopus laevis), and chicken (Gallus gallus) embryos to transient perturbations,
      namely heat shock and inhibitor treatments during three developmental periods
      [early (represented by blastula and gastrula), pharyngula, and late], we found
      that the early stages showed the highest rate of lethal phenotypes in all three
      species. This result was corroborated by perturbation with genetic mutations. By
      tracking the survival rate of wild-type embryos and embryos with genetic
      mutations induced by UV irradiation in zebrafish and African clawed frogs, we
      found that the highest decrease in survival rate was at the early stages
      particularly around gastrulation in both these species. Conclusion: In opposition
      to the "mid-embryonic lethality hypothesis," our results consistently showed that
      the stage with the highest lethality was not around the conserved pharyngula
      period, but rather around the early period in all the vertebrate species tested.
      These results suggest that negative selection by embryonic lethality could not
      explain hourglass-like conservation of animal embryos. This highlights the
      potential contribution of alternative mechanisms such as the diversifying effect
      of positive selections against earlier and later stages, and developmental
      constraints which lead to conservation of mid-embryonic stages.

PMID- 29568480
TI  - The Importance of Assessing Nutritional Status to Ensure Optimal Recovery during
      the Chronic Phase of Stroke.
AB  - Background: Despite evidence that many of the consequences of stroke that hinder
      recovery (i.e., obesity, muscle atrophy, and functional declines) have
      nutritionally modifiable behavior components, little attention has been focused
      on the significance of nutrition beyond the acute phase of stroke. Objective:
      This literature review summarizes the evidence for and against the influence of
      nutrition on optimal recovery and rehabilitation in chronic (>6 months) stroke.
      Results: The literature, which is mainly limited to cross-sectional studies,
      suggests that a suboptimal nutritional status, including an excess caloric
      intake, reduced protein intake, and micronutrient deficiencies, particularly the
      B-vitamins, vitamin D, and omega 3 fatty acids, may have deleterious effects on
      metabolic, physical, and psychological functioning in chronic stroke survivors.
      Conclusions: Careful evaluation of dietary intake, especially among those with
      eating disabilities and preexisting malnutrition, may aid in the identification
      of individuals at increased nutritional risk through which early intervention may
      benefit recovery and rehabilitation and prevent further complications after
      stroke.

PMID- 29568481
TI  - Impaired Inflammatory Response to LPS in Type 2 Diabetes Mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a severe health problem worldwide, reaching
      epidemic levels. High susceptibility to infections of T2DM patients indicates
      dysregulated immune responses to pathogens. However, innate immune responses,
      including monocyte functions, in T2DM are poorly investigated. Therefore, in this
      study we aimed to assess lipopolysaccharide- (LPS-) induced immune responses of
      circulating monocytes from T2DM patients. The results showed that monocytes from
      T2DM were hyporesponsive to LPS challenge as reflected by significantly
      suppressed secretion of TNFalpha (p < 0.01) and expression of CD11b (p < 0.001)
      and TLR4 (p < 0.001) compared to those in monocytes from healthy subjects.
      Furthermore, LPS-induced IL-10 levels were similar in diabetic and healthy
      supernatants, while expression levels of CD163 were found to be downregulated on
      monocytes from T2DM (p < 0.001) suggesting impaired ability of monocytes to
      switch their phenotype to anti-inflammatory. Taken together, our results suggest
      compromised function of monocytes in T2DM, which may explain, at least partly,
      high incidence of infection in these patients.

PMID- 29568483
TI  - Transplantation of endothelial progenitor cells attenuated paraquat-induced acute
      lung injury via miR-141-3p-Notch-Nrf2 axis.
AB  - Background: Paraquat (PQ) presents with high toxicity for humans and animals, and
      the lungs become the main target organ by the poisoning of PQ leading to acute
      lung injury. Endothelial progenitor cells (EPCs) were proved to have the repair
      function on acute lung injury (ALI). We aimed to invatigate the underlying
      mechanism of EPCs in PQ-induced ALI involving miR-141-3p. Methods: Endothelial
      progenitor cells were isolated from peripheral blood of C57BL/6J mice and
      identified by flow cytometry. Lung wet-to-dry (W/D) weight ratios, lung injury
      score and the number of total leukocyte and the number of neutrophils in BALF
      were used to analyze the degree of lung injury. The transfection was performed
      with Lipofectamine 2000. The levels of miRNA and mRNA were determined by qRT-PCR,
      and the protein levels were detected by Western blot assay. Results: Endothelial
      progenitor cells alleviated lung wet-to-dry (W/D) weight ratios, lung injury
      score and the number of total leukocyte and the number of neutrophils in BALF in
      PQ-induced ALI mice. EPCs inhibited miR-141-3p expression, and enhanced the
      levels of Notch-Nrf2 axis in PQ-induced ALI mice. MiR-141-3p knockdown reversed
      the PQ induced-inhibition on Notch-1 and Hesr1 expression. MiR-141-3p over
      expression could inhibit the expression of Notch-1 pathway significantly in the
      pulmonary epithelial cell line MLE-12. Both miR-141-3p over-expression and si
      Notch-1 abolished the protection effect of EPCs on lung injury induced by PQ in
      vivo. Conclusions: Endothelial progenitor cells could provide therapeutic effect
      on PQ-induced ALI via miR-141-3p-Notch-Nrf2 Axis.

PMID- 29560252
TI  - Rheumatoid arthritis in an adult patient with mosaic distal 18q-, 18p- and ring
      chromosome 18.
AB  - Ring chromosome 18 has a highly variable phenotype, depending on the extent of
      distal arm deletions. It is most commonly presented as a combination of 18p- and
      distal 18q- syndrome. IgA deficiency and autoimmune diseases have been previously
      described in these patients. Seven cases of juvenile rheumatoid arthritis (JRA)
      have been reported. Here we report the first case of late onset rheumatoid
      arthritis (RA) in a 32 year old Dominican woman with hypothyroidism, vitiligo,
      IgA deficiency, interstitial lung disease (ILD), cystic bronchiectasis, and
      features consistent with ringed 18, 18p- and distal 18q syndrome.  The multiple
      autoimmune findings in our patient lends further support to the idea of loci on
      chromosome 18 playing a role in autoimmune disease expression. Late onset RA and
      ILD in a patient with chromosome 18 abnormalities are novel findings and are
      additional conditions to be aware of in this population.

PMID- 29568484
TI  - How frequent are non-evidence-based health care beliefs in chiropractic students
      and do they vary across the pre-professional educational years.
AB  - Background: Evidence suggests that a students' beliefs already prior to entering
      a program may be important as a determinant in sustaining unsuitable health care
      beliefs. Our objectives were to investigate the proportion of Australian
      chiropractic students who hold non-evidence-based beliefs in the first year of
      study and the extent to which they may be involved in non-musculoskeletal health
      conditions. Finally, to see if this proportion varies over the course of the
      chiropractic program. Method: In 2016, students from two Australian chiropractic
      programs answered a questionnaire on how often they would give advice on five
      common health conditions in their future practices as well as their opinion on
      whether chiropractic spinal adjustments could prevent or help seven health
      related conditions. Results: From a possible 831 students, 444 responded (53%).
      Students were highly likely to offer advice (often/quite often) on a range of non
      musculoskeletal conditions. The proportions were lowest in first year and highest
      the final year. Also, high numbers of students held non-evidence-based beliefs
      about 'chiropractic spinal adjustments' which tended to occur in gradually
      decreasing in numbers in sequential years, except for fifth year when a reversal
      of the pattern occurred. Conclusions: New strategies are required for
      chiropractic educators if they are to produce graduates who understand and
      deliver evidence-based health care and able to be part of the mainstream health
      care system.

PMID- 29560253
TI  - Evaluation of Trichoderma spp., Pseudomonasfluorescens and Bacillus subtilis for
      biological control of Ralstonia wilt of tomato.
AB  - Background:Ralstonia spp. is a major pathogenic microbe for tomato, which invades
      the roots of diverse plant hosts and colonizes xylem vessels causing wilt,
      especially in tropical, subtropical and warm-temperate regions. Ralstonia spp.
      produces several virulence factors helping it to invade the plant's natural
      defense mechanism. Native isolates of Trichoderma spp., Pseudomonas fluorescens
      and Bacillus subtilis can be used as biocontrol agents to control the bacterial
      wilt and combined application of these beneficial microbes can give better
      results. Methods: Bacterial wilt infection in the field was identified by field
      experts and the infected plant part was used to isolate Ralstonia spp. in CPG
      media and was positively identified. Subsequently, the efficacy of the biocontrol
      agents was tested and documented using agar well diffusion technique and digital
      microscopy. 2ml of the microbial concentrate (10 9 cells/ml) was mixed in one
      liter of water and was applied in the plant root at the rate of 100 ml per plant
      as a treatment method. Results: It was observed that the isolated Trichoderma
      spp. AA2 and Pseudomonas fluorescens PFS were most potent in inhibiting the
      growth of Ralstonia spp. , showing ZOI 20.67 mm and 22.33 mm, respectively.
      Digital microscopy showed distinct inhibitory effect on the growth and survival
      of Ralstonia spp . The results from the field data indicated that Trichoderma
      spp. and Pseudomonas fluorescens alone were able to prevent 92% and 96% of the
      infection and combination of both were more effective, preventing 97% of
      infection. Chemical control methods prevented 94% of infection. Bacillus subtilis
      could only prevent 84 % of the infection.   Conclusions: Antagonistic effect
      against Ralstonia spp. shown by native isolates of Trichoderma spp. and P.
      fluorescens manifested the promising potential as biocontrol agents. Combined
      application gave better results. Results shown by Bacillus subtilis were not
      significant.

PMID- 29568482
TI  - Presenting a New Standard Drug Model for Turmeric and Its Prized Extract,
      Curcumin.
AB  - Various parts of the turmeric plant have been used as medicinal treatment for
      various conditions from ulcers and arthritis to cardiovascular disease and
      neuroinflammation. The rhizome's curcumin extract is the most studied active
      constituent, which exhibits an expansive polypharmacology with influence on many
      key inflammatory markers. Despite the expansive reports of curcucmin's
      therapeutic value, clinical reliability and research repeatability with curcumin
      treatment are still poor. The pharmacology must be better understood and reliably
      mapped if curcumin is to be accepted and used in modern medical applications.
      Although the polypharmacology of this extract has been considered, in mainstream
      medicine, to be a drawback, a perspective change reveals a comprehensive and even
      synergistic shaping of the NF-kB pathway, including transactivation. Much of the
      inconsistent research data and unreliable clinical outcomes may be due to a lack
      of standardization which also pervades research standard samples. The possibility
      of other well-known curcumin by-products contributing in the polypharmacology is
      also discussed. A new flowchart of crosstalk in transduction pathways that lead
      to shaping of nuclear NF-kB transactivation is generated and a new calibration or
      standardization protocol for the extract is proposed which could lead to more
      consistent data extraction and improved reliability in therapy.

PMID- 29560254
TI  - Case Report: Dual nebulised antibiotics among adults with cystic fibrosis and
      chronic Pseudomonas infection.
AB  - Pulmonary exacerbations in adults with cystic fibrosis (CF) and chronic
      Pseudomonas aeruginosa (Psae) infection are usually treated with dual intravenous
      antibiotics for 14 days, despite the lack of evidence for best practice.
      Intravenous antibiotics are commonly associated with various systemic adverse
      effects, including renal failure and ototoxicity. Inhaled antibiotics are less
      likely to cause systematic adverse effects, yet can achieve airway concentrations
      well above conventional minimum inhibitory concentrations. Typically one inhaled
      antibiotic is used at a time, but dual inhaled antibiotics (i.e. concomitant use
      of two different inhaled antibiotics) may have synergistic effect and achieve
      better results in the treatment of exacerbations. We presented anecdotal evidence
      for the use of dual inhaled antibiotics as an acute treatment for exacerbations,
      in the form of a case report. A female in her early thirties with CF and chronic
      Psae infection improved her FEV 1 by 5% and 2% with two courses of dual inhaled
      antibiotics to treat exacerbations in 2016. In contrast, her FEV 1 changed by 2%,
      -2%, 0% and 2%, respectively, with four courses of dual intravenous antibiotics
      in 2016. Baseline FEV 1 was similar prior to all six courses of treatments. The
      greater FEV 1 improvements with dual inhaled antibiotics compared to dual
      intravenous antibiotics suggest the potential role of using dual inhaled
      antibiotics to treat exacerbations among adults with CF and chronic Psae
      infection, especially since a greater choice of inhaled anti-pseudomonal
      antibiotics is now available. A previous study in 1985 has looked at the
      concomitant administration of inhaled tobramycin and carbenicillin, by
      reconstituting antibiotics designed for parenteral administration. To our
      knowledge, this is the first literature to describe the concomitant use of two
      different antibiotics specifically developed for delivery via the inhaled route.

PMID- 29568490
TI  - Case Report: Non-infectious causes of palmoplantar rashes, what to consider.
AB  - Background: Palm and sole skin eruptions have a broad differential diagnosis. It
      is particularly important to recognize common causes as well as their association
      with certain chemotherapy regimens such as Capecitabine. Case report: A 79-year
      old woman presented with a painful rash on her hands and feet for 1 week. She had
      metastatic colon cancer and was in her third week of treatment with capecitabine.
      Her diagnosis was a medication side-effect from chemotherapy. Capecitabine was
      stopped and she had some clinical improvement over the next two days. She was
      discharged with oncology follow up for resumption of Capecitabine at a lower dose
      with improvement in her rash 3 weeks later.? Discussion: Skin rashes are a
      commonly encountered complaint in patients in the inpatient and outpatient
      setting. It is important to maintain a broad differential diagnosis in those with
      rashes of the palmoplantar surfaces of the hands and feet. Recognizing skin
      changes as a possible manifestation of underlying malignancy or a medication side
      effect is key in appropriate diagnosis and treatment.

PMID- 29568488
TI  - Recent advances in understanding acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse lung
      injury, which results in increased pulmonary vascular permeability and loss of
      aerated lung tissue. This causes bilateral opacity consistent with pulmonary
      edema, hypoxemia, increased venous admixture, and decreased lung compliance such
      that patients with ARDS need supportive care in the intensive care unit to
      maintain oxygenation and prevent adverse outcomes. Recently, advances in
      understanding the underlying pathophysiology of ARDS led to new approaches in
      managing these patients. In this review, we want to focus on recent scientific
      evidence in the field of ARDS research and discuss promising new developments in
      the treatment of this disease.

PMID- 29568489
TI  - Ten steps to get started in Genome Assembly and Annotation.
AB  - As a part of the ELIXIR-EXCELERATE efforts in capacity building, we present here
      10 steps to facilitate researchers getting started in genome assembly and genome
      annotation. The guidelines given are broadly applicable, intended to be stable
      over time, and cover all aspects from start to finish of a general assembly and
      annotation project. Intrinsic properties of genomes are discussed, as is the
      importance of using high quality DNA. Different sequencing technologies and
      generally applicable workflows for genome assembly are also detailed. We cover
      structural and functional annotation and encourage readers to also annotate
      transposable elements, something that is often omitted from annotation workflows.
      The importance of data management is stressed, and we give advice on where to
      submit data and how to make your results Findable, Accessible, Interoperable, and
      Reusable (FAIR).

PMID- 29560255
TI  - An explanatory model for the concept of mental health in Iranian youth.
AB  - Background: Mental health is considered as an integral and essential component of
      overall health. Its determinants and related factors are one of the most
      important research priorities, especially in adolescents and young people. Using
      a qualitative approach, the present study aimed to identify factors affecting the
      mental health of youth in Iran. Methods: In 2017, following content analysis
      principles, and using semi-structured in-depth interviews, we conducted a
      qualitative study exploring the opinions of young people about mental health. A
      targeted sampling method was used, and participants were young volunteers aged 18
      to 30 who were selected from Tehran province, Iran. Inclusion criteria for
      participants was willingness to participate in the study, and ability to express
      their experiences. Data collection was done with individual in-depth interviews.
      According to the explanatory model, the interviews were directed toward the
      concept of mental health and path of causality and auxiliary behaviors. Results:
      21 young adults participated, who met the study inclusion criteria, of whom 12
      participants were male. Their mean age was 24.4 +/- 0.41 years and their
      education varied from primary school to Master's degree. Mental health was
      considered as mental well-being and a sense of satisfaction and efficacy, not
      only the presence of a disease or mental disorder. Based on the opinions of the
      interviewees, three factors of personal characteristics, family and society are
      involved in mental health. Individual factors were associated with behavioral and
      physical problems. One of the most important issues was revealed as tensions in
      societal and family conflicts. Economic problems and unemployment of young people
      were also extracted from the social factor. Conclusion: In Iran, social factors
      such as jobs for the unemployed and job security are considered as important
      determinants in the mental health of young people.

PMID- 29568492
TI  - Using regulatory genomics data to interpret the function of disease variants and
      prioritise genes from expression studies.
AB  - The identification of therapeutic targets is a critical step in the research and
      developement of new drugs, with several drug discovery programmes failing because
      of a weak linkage between target and disease. Genome-wide association studies and
      large-scale gene expression experiments are providing insights into the biology
      of several common and complex diseases, but the complexity of transcriptional
      regulation mechanisms often limit our understanding of how genetic variation can
      influence changes in gene expression. Several initiatives in the field of
      regulatory genomics are aiming to close this gap by systematically identifying
      and cataloguing regulatory elements such as promoters and enhacers across
      different tissues and cell types. In this Bioconductor workflow, we will explore
      how different types of regulatory genomic data can be used for the functional
      interpretation of disease-associated variants and for the prioritisation of gene
      lists from gene expression experiments.

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- 29568494
TI  - Hubris and Sciences.
AB  - There has been an increasing awareness of the importance of leadership and
      decision making, including scientists and academics, over recent times. By whom
      and how decisions are made can have serious implications across all levels of
      society. Several people have been successful in their life and have been
      inflicted by excessive pride and self-confidence. There are times when the
      manifestations of such behaviours demonstrate noticeable signs of narcissism and
      on extreme cases, hubris. Hubris is an old concept originated from the Greek
      mythology.  The risk of hubris affects politicians, leaders in business,
      scientists, academia, the military, entertainers, athletes and doctors (among
      many others). Power, especially absolute and unchecked power, is intoxicating and
      is manifested behaviourally in a variety of ways, ranging from amplified
      cognitive functions to lack of inhibition, poor judgment, extreme narcissism,
      deviant behaviour, and even cruelty. Hubristic behaviour of overconfidence,
      extreme pride together with an unwillingness to disregard advice makes powerful
      people in leadership positions to over-reach themselves with negative
      consequences for themselves and others. As the dangerous consequences of
      hubristic behaviours become more apparent and well described it is imperative
      that individuals, organisations and governments act to prevent such phenomena.
      Responsible leaders, including acclaimed scientists should exercise greater
      humility to the complexity and inherent uncertainty of their activities and
      strive to seek out and challenge hubristic behaviours.

PMID- 29560256
TI  - Reflections on the use of the World Health Organization's (WHO) OneHealth Tool:
      Implications for health planning in low and middle income countries (LMICs).
AB  - The World Health Organization (WHO) launched the OneHealth Tool (OHT) to help low
      and middle income countries to develop their capacities for sector-wide priority
      setting. In 2016, we sought to use the OHT to aid the Philippine Health Insurance
      Corporation (PHIC), the national health insurer of the Philippines, in decisions
      to expand benefit packages using cost-effectiveness analyses. With technical
      support from the WHO, we convened health planning officers from the Philippine
      Department of Health (DOH) and the Philippine Health Insurance Corporation (PHIC)
      conduct generalized cost-effective analyses (GCEA) of selected un-financed
      noncommunicable disease interventions using OHT. We collected epidemiological and
      cost data through health facility surveys, review of literature such as cost
      libraries and clinical practice guidelines, and expert consultations. Although we
      were unable to use GCEA results directly to set policy, we learnt important
      policy lessons which we outline here that might help inform other countries
      looking to inform service coverage decisions. Additionally, the entire process
      and GCEA visualizations helped high-level policymakers in the health sector, who
      have traditionally relied on ad hoc decision making, to realize the need for a
      systematic and transparent priority-setting process that can continuously provide
      the evidence needed to inform service coverage decisions.

PMID- 29568497
TI  - Progress and challenges in TB vaccine development.
AB  - The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection
      against tuberculosis (TB) disease, and although imperfect, BCG is proof that
      vaccine mediated protection against TB is a possibility. A new TB vaccine is,
      therefore, an inevitability; the question is how long will it take us to get
      there? We have made substantial progress in the development of vaccine platforms,
      in the identification of antigens and of immune correlates of risk of TB disease.
      We have also standardized animal models to enable head-to-head comparison and
      selection of candidate TB vaccines for further development.  To extend our
      understanding of the safety and immunogenicity of TB vaccines we have performed
      experimental medicine studies to explore route of administration and have begun
      to develop controlled human infection models. Driven by a desire to reduce the
      length and cost of human efficacy trials we have applied novel approaches to
      later stage clinical development, exploring alternative clinical endpoints to
      prevention of disease outcomes. Here, global leaders in TB vaccine development
      discuss the progress made and the challenges that remain. What emerges is that,
      despite scientific progress, few vaccine candidates have entered clinical trials
      in the last 5 years and few vaccines in clinical trials have progressed to
      efficacy trials. Crucially, we have undervalued the knowledge gained from our
      "failed" trials and fostered a culture of risk aversion that has limited new
      funding for clinical TB vaccine development. The unintended consequence of this
      abundance of caution is lack of diversity of new TB vaccine candidates and
      stagnation of the clinical pipeline. We have a variety of new vaccine platform
      technologies, mycobacterial antigens and animal and human models.  However, we
      will not encourage progression of vaccine candidates into clinical trials unless
      we evaluate and embrace risk in pursuit of vaccine development.

PMID- 29568498
TI  - Case Report: Evaluation strategies and cognitive intervention: the case of a
      monovular twin child affected by selective mutism.
AB  - The present work describes the assessment process, evaluation strategies, and
      cognitive intervention on a 9 years old child with selective mutism (SM), a
      monovular twin of a child also affected by mutism. Currently, the cognitive
      behavioral multimodal treatment seems the most effective therapeutic approach for
      children diagnosed with selective mutism (Capobianco & Cerniglia, 2018). The
      illustrated case confirms the role of biological factors involved in mutacic
      disorder but also highlights the importance of environmental influences in the
      maintenance of the disorder with respect to relational and contextual dynamics
      (e.g. complicity between sisters, family relationships). The article discusses
      furthermore the importance of an early diagnosis as a predictor of positive
      treatment outcomes.

PMID- 29568496
TI  - Missing the egocentric spatial reference: a blank on the map.
AB  - Egocentric (self-centered) and allocentric (viewpoint independent)
      representations of space are essential for spatial navigation and wayfinding.
      Deficits in spatial memory come with age-related cognitive decline, are marked in
      mild cognitive impairment (MCI) and Alzheimer's disease (AD), and are associated
      with cognitive deficits in autism. In most of these disorders, a change in the
      brain areas engaged in the spatial reference system processing has been
      documented. However, the spatial memory deficits observed during physiological
      and pathological aging are quite different. While patients with AD and MCI have a
      general spatial navigation impairment in both allocentric and egocentric
      strategies, healthy older adults are particularly limited in the allocentric
      navigation, but they can still count on egocentric navigation strategy to solve
      spatial tasks. Therefore, specific navigational tests should be considered for
      differential diagnosis between healthy and pathological aging conditions.
      Finally, more research is still needed to better understand the spatial abilities
      of autistic individuals.

PMID- 29568499
TI  - NFAT control of immune function: New Frontiers for an Abiding Trooper.
AB  - Nuclear factor of activated T cells (NFAT) was first described almost three
      decades ago as a Ca 2+/calcineurin-regulated transcription factor in T cells.
      Since then, a large body of research uncovered the regulation and physiological
      function of different NFAT homologues in the immune system and many other
      tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing
      mainly on its function in humoral immune responses, immunological tolerance, and
      the regulation of immune metabolism.

PMID- 29568500
TI  - Radial glial cells in the adult dentate gyrus: what are they and where do they
      come from?
AB  - Adult neurogenesis occurs in the dentate gyrus in the mammalian hippocampus.
      These new neurons arise from neural precursor cells named radial glia-like cells,
      which are situated in the subgranular zone of the dentate gyrus. Here, we review
      the emerging topic of precursor heterogeneity in the adult subgranular zone. We
      also discuss how this heterogeneity may be established during development and
      focus on the embryonic origin of the dentate gyrus and radial glia-like stem
      cells. Finally, we discuss recently developed single-cell techniques, which we
      believe will be critical to comprehensively investigate adult neural stem cell
      origin and heterogeneity.

PMID- 29568501
TI  - Advances in understanding the molecular basis of skin fragility.
AB  - Skin fragility refers to a large group of conditions in which the ability of the
      skin to provide protection against trivial mechanical trauma is diminished,
      resulting in the formation of blisters, erosions, wounds, or scars. Acquired and
      physiological skin fragility is common; genetic disorders are rare but give
      insight into the molecular mechanisms ensuring skin stability. The paradigm is
      represented by inherited epidermolysis bullosa. This review is focused on recent
      advances in understanding the molecular basis of genetic skin fragility,
      including emerging concepts, controversies, unanswered questions, and opinions of
      the author. In spite of the advanced knowledge on the genetic causes of skin
      fragility, the molecular pathology is still expanding. Open questions in
      understanding the molecular basis of genetic skin fragility are the following:
      what are the causes of phenotypes which remain genetically unsolved, and what are
      the molecular modifiers which might explain phenotypic differences among
      individuals with similar mutations?  New mutational mechanisms and new genes have
      recently been discovered and are briefly described here. Comprehensive next
      generation sequencing-based genetic testing improved mutation detection and
      facilitated the identification of the genetic basis of unclear and new
      phenotypes. Characterization of the biochemical and cell biological consequences
      of the genetic variants is challenging and laborious but may represent the basis
      for personalized therapeutic approaches. Molecular modifiers of skin fragility
      have been uncovered in particular animal and genetic models but not in larger
      cohorts of patients. This scientific progress is the basis for revisions of the
      epidermolysis bullosa classification and for innovative therapeutic approaches
      designed for this intractable condition.

PMID- 29568502
TI  - Associations between atopic dermatitis and other disorders.
AB  - Atopic dermatitis is a heterogeneous, chronic, and inflammatory skin disease that
      is associated with a profound symptom burden. Recent studies have demonstrated
      associations between atopic dermatitis and a number of multi-organ and systemic
      disorders. The origin of these comorbid conditions is likely multifactorial, with
      combined effects of skin-barrier disruption, immune dysregulation, intense
      symptoms, and iatrogenic complications. Some of these comorbid conditions appear
      to be related to the underlying severity of atopic dermatitis and inadequate
      disease control. This review will summarize recent developments in the
      understanding of the comorbid health disorders associated with atopic dermatitis,
      particularly infections, sleep disturbances, and cardiovascular disease.

PMID- 29568503
TI  - Recent advances in the management of large and complex colonic polyps.
AB  - The endoscopic management of large colonic polyps is a rapidly changing field.
      Rapid evolution in endoscopic techniques and skills has resulted in diminishing
      the role of surgery in the management of larger and complex polyps. This is
      resulting in organ preservation for many who otherwise would have undergone
      surgery. However, it also poses new challenges. This article reviews these new
      advances and the developments which are overcoming these difficulties.

PMID- 29568504
TI  - Renal cell carcinoma: a review of biology and pathophysiology.
AB  - Over the past decade, our understanding of the biology and pathophysiology of
      renal cell carcinoma (RCC) has improved significantly. Insight into the disease
      process has helped us in developing newer therapeutic approaches toward RCC. In
      this article, we review the various genetic and immune-related mechanisms
      involved in the pathogenesis and development of this cancer and how that
      knowledge is being used to develop therapeutic targeted drugs for the treatment
      of RCC. The main emphasis of this review article is on the most common genetic
      alterations found in clear cell RCC and how various drugs are currently targeting
      such pathways. This article also looks at the role of the immune system in
      allowing the growth of RCC and how the immune system can be manipulated to
      reactivate cytotoxic immunity against RCC.

PMID- 29568506
TI  - Recent advances in antiviral interferon-stimulated gene biology.
AB  - The interferon response protects cells from invading viral pathogens by
      transcriptionally inducing the expression of interferon-stimulated genes (ISGs),
      some of which encode effectors with varied antiviral functions. As screening
      technologies improve and mouse model development quickens, more ISGs are
      continually being identified, characterized mechanistically, and evaluated for
      protective roles in vivo. This review highlights selected recent findings of ISG
      effectors that contribute to our understanding of the interferon antiviral
      response.

PMID- 29568505
TI  - Cutting down the time to identify challenging tumor therapeutic targets and drug
      combinations using synthetic lethal approaches.
AB  - Cancer drug discoverers and developers are blessed and cursed with a plethora of
      drug targets in the tumor cells themselves and the surrounding stromal elements.
      This bounty of targets has, at least in part, inspired the rapid increase in the
      number of clinically available small-molecule, biological, and cellular therapies
      for solid and hematological malignancies. Among the most challenging questions in
      cancer therapeutics, especially for small molecules, is how to approach loss-of
      function gene mutations or deletions that encode tumor suppressors. A second
      mounting question is what are the optimal drug combinations. This article will
      briefly review the recent advances in exploiting in vitro and in vivo synthetic
      lethal screens to expose cancer pharmacological targets with the goal of
      developing new drug combinations.

PMID- 29568507
TI  - Separation of Saturated Fatty Acids and Fatty Acid Methyl Esters with Epoxy
      Nanofiltration Membranes.
AB  - Epoxy nanofiltration membranes were fabricated by the step polymerization of a
      primary diamine and a diepoxide or triepoxide conomomer. Membrane selectivity and
      flux were tuned by changing the identity of the diepoxides and by increasing the
      concentration of triepoxides in the polymerization. The membranes were used to
      separate even chain length saturated fatty acids (FAs) and saturated fatty acid
      methyl esters (FAMEs) that possessed molecular weights between 80 - 300 g mol-1.
      Our membranes show excellent selectivities of up to 100:1 for the separation of
      the C4-C18 FAMEs. The flux of the FAMEs through the membranes showed an
      exponential dependence based on the number of carbons. Fabrication of thin epoxy
      membranes with thicknesses of 150 nm allowed for an increase in flux of FAMEs
      through the membrane and demonstrated that these separations can be used under
      industrially relevant conditions.

PMID- 29568508
TI  - Targeting protein-loaded CB[8]-mediated supramolecular nanocarriers to cells.
AB  - Supramolecular amphiphiles, consisting of ternary complexes of cucurbit[8]uril
      (CB[8]), an alkylated paraquat derivative and a tetraethylene glycol
      functionalized azobenzene, self-assemble into vesicles of about 200 nm in
      diameter. The outer surface of the vesicles was functionalized with cell
      targeting ligands. These vesicles were employed for loading and delivery of
      proteins into cells. Supramolecular amphiphile-derived vesicles show great
      promise as nanocarriers of functional molecules to be transferred into cells.

PMID- 29568509
TI  - 17O solid-state NMR spectroscopy of A2B2O7 oxides: quantitative isotopic
      enrichment and spectral acquisition?
AB  - The potential of 17O NMR spectroscopy for the investigation of A2B2O7 ceramic
      oxides important in the encapsulation of radioactive waste is demonstrated, with
      post-synthetic enrichment by exchange with 17O2 gas. For Y2Sn2O7, Y2Ti2O7 and
      La2Sn2O7 pyrochlores, enrichment of the two distinct O species is clearly non
      quantitative at lower temperatures (~700  degrees C and below) and at shorter
      times, despite these being used in prior work, with preferential enrichment of
      OA2B2 favoured over that of OA4. At higher temperatures, the 17O NMR spectra
      suggest that quantitative enrichment has been achieved, but the integrated signal
      intensities do not reflect the crystallographic 1 : 6 (O1 : O2) ratio until
      corrected for differences in T1 relaxation rates and, more importantly, the
      contribution of the satellite transitions. 17O NMR spectra of Y2Zr2O7 and Y2Hf2O7
      defect fluorites showed little difference with any variation in enrichment
      temperature or time, although an increase in the absolute level of enrichment (up
      to ~7.5%) was observed at higher temperature. DFT calculations show that the six
      distinct resonances observed cannot be assigned unambiguously, as each has
      contributions from more than one of the five possible next nearest neighbour
      environments. For La2Ti2O7, which adopts a layered perovskite-like structure,
      little difference in the spectral intensities is observed with enrichment time or
      temperature, although the highest absolute levels of enrichment (~13%) were
      obtained at higher temperature. This work demonstrates that 17O NMR has the
      potential to be a powerful probe of local structure and disorder in oxides, but
      that considerable care must be taken both in choosing the conditions for 17O
      enrichment and the experimental acquisition parameters if the necessary
      quantitative measurements are to be obtained for more complex systems.

PMID- 29568510
TI  - Flexible corner cube retroreflector array for temperature and strain sensing.
AB  - Optical sensors for detecting temperature and strain play a crucial role in the
      analysis of environmental conditions and real-time remote sensing. However, the
      development of a single optical device that can sense temperature and strain
      simultaneously remains a challenge. Here, a flexible corner cube retroreflector
      (CCR) array based on passive dual optical sensing (temperature and strain) is
      demonstrated. A mechanical embossing process was utilised to replicate a three
      dimensional (3D) CCR array in a soft flexible polymer film. The fabricated
      flexible CCR array samples were experimentally characterised through reflection
      measurements followed by computational modelling. As fabricated samples were
      illuminated with a monochromatic laser beam (635, 532, and 450 nm), a triangular
      shape reflection was obtained at the far-field. The fabricated flexible CCR array
      samples tuned retroreflected light based on external stimuli (temperature and
      strain as an applied force). For strain and temperature sensing, an applied force
      and temperature, in the form of weight suspension, and heat flow was applied to
      alter the replicated CCR surface structure, which in turn changed its optical
      response. Directional reflection from the heated flexible CCR array surface was
      also measured with tilt angle variation (max. up to 10 degrees ). Soft polymer
      CCRs may have potential in remote sensing applications, including measuring the
      temperature in space and in nuclear power stations.

PMID- 29568511
TI  - A novel method for the collection of nanoscopic vesicles from an organotypic
      culture model.
AB  - Nanovesicles, exosomes and other membrane bound particles excreted by cells are
      currently gaining research attention since they have been shown to play a
      significant role in many biologically related processes. Vesicles are now thought
      to mediate cellular communication, transmission of some diseases and
      pathologically mediated calcification. Matrix vesicles have long been proposed to
      be central to the controlled mineralisation of bone. They remain relatively
      poorly studied, however, since they are challenging to extract from biological
      media. One difficulty is the presence of a mineral content in comparison to pure
      lipid vesicles, meaning that standard separation process such as
      ultracentrifugation are unable to precisely separate on the basis of size or
      weight. In this paper we report the separation of matrix vesicles from an
      organotypic bone culture system using a process of immunoprecipitation. Matrix
      vesicles were extracted using polymeric beads that were modified with an antibody
      for tissue non-specific alkaline phosphatase (TNALP), a surface marker abundant
      in bone-derived vesicles. The vesicles isolated were positive for adenosine
      triphosphate (ATP), the substrate for TNALP and were demonstrated to have a high
      binding affinity to type I collagen, the principal collagen type found in bone.
      This protocol enables more detailed study of the process and regulation of
      mineralisation.

PMID- 29568512
TI  - Electronic structure, polaron formation, and functional properties in transition
      metal tungstates.
AB  - Transition-metal tungstates MWO4 (M = Co, Ni, Cu, Zn) have applications in many
      areas, including supercapacitors. A good understanding of the electronic
      structure is essential to understanding their functional properties. Here, we
      report a first-principles study of the materials using hybrid density-functional
      calculations. The electronic structure is analyzed with a focus on the nature of
      the electronic states near the band edges. We find that hole polarons can form at
      the Co lattice site in CoWO4 and the O site in NiWO4, CuWO4, and ZnWO4, resulting
      in the formation of Co3+ in the former and O- in the latter. The electrochemical
      activity observed in certain tungstate compounds, but not in others, appears to
      be related to the ability to form hole polarons on the transition-metal ions. The
      formation energy and migration barrier of the hole polaron in CoWO4 are also
      calculated and the results are employed to understand the reported p-type
      conductivity.

PMID- 29568513
TI  - Assaying sensory ciliopathies using calcium biosensor expression in zebrafish
      ciliated olfactory neurons.
AB  - Background: Primary cilia mediate signal transduction by acting as an organizing
      scaffold for receptors, signalling proteins and ion channels. Ciliated olfactory
      sensory neurons (OSNs) organize olfactory receptors and ion channels on cilia and
      generate a calcium influx as a primary signal in odourant detection. In the
      zebrafish olfactory placode, ciliated OSNs and microvillus OSNs constitute the
      major OSN cell types with distinct odourant sensitivity. Methods: Using
      transgenic expression of the calcium biosensor GCaMP5 in OSNs, we analysed
      sensory cilia-dependent odour responses in live zebrafish, at individual cell
      resolution. oval/ift88 mutant and ift172 knockdown zebrafish were compared with
      wild-type siblings to establish ciliated OSN sensitivity to different classes of
      odourants. Results: oval/ift88 mutant and ift172 knockdown zebrafish showed fewer
      and severely shortened OSN cilia without a reduction in OSN number. The fraction
      of responding OSNs and response amplitudes to bile acids and food odour, both
      sensed by ciliated OSNs, were significantly reduced in ift88 mutants and ift172
      deficient embryos, while the amino acids responses were not significantly
      changed. Conclusions: Our approach presents a quantitative model for studying
      sensory cilia signalling using zebrafish OSNs. Our results also implicate ift172
      deficiency as a novel cause of hyposmia, a reduced sense of smell, highlighting
      the value of directly assaying sensory cilia signalling in vivo and supporting
      the idea that hyposmia can be used as a diagnostic indicator of ciliopathies.

PMID- 29568514
TI  - Prevalence and antibiotic resistance of bacteria isolated from the cerebrospinal
      fluid of neurosurgical patients at Peking Union Medical College Hospital.
AB  - Background: Postoperative central nervous system infections (PCNSIs) represent a
      serious complication, and the timely use of antibiotics guided by the
      identification of the causative pathogens and their antibiotic sensitivities is
      essential for treatment. However, there are little data regarding the prevalence
      of PCNSI pathogens in China. The aim of this study is to investigate the features
      of pathogens in patients with PCNSIs, which could help clinicians to choose the
      appropriate empirical antibiotic therapy. Methods: We retrospectively examined
      the positive CSF cultures in patients who underwent craniotomy between January
      2010 and December 2015. We collected data, including demographic characteristics,
      type of neurosurgery, laboratory data, causative organisms and antimicrobial
      susceptibility testing results. Results: A total of 62 patients with 90 isolates
      out of 818 patients with 2433 CSF culture samples were available for data
      analysis. The estimated incidence and culture-positive rate of PCNSIs were
      approximately 0.9 and 7.5%, respectively. The predominant organism was coagulase
      negative staphylococci, of which most were methicillin-resistant coagulase
      negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid,
      rifampicin and amoxicillin-clavulanate. Acinetobacter baumannii was the most
      frequent causative Gram-negative agent and was resistant to 12 out of 18
      antimicrobials tested. The sensitivity rates for tigecycline and minocycline were
      only 40 and 33%, respectively. Conclusion: PCNSIs could lead to high mortality.
      Although the MRCoNS were the predominant organism, the management of
      Acinetobacter baumannii was a major clinical challenge with few effective
      antimicrobials in PCNSIs.

PMID- 29568515
TI  - Prevalence and molecular characterization of Staphylococcus aureus from human
      stool samples.
AB  - Background: To determine the prevalence of intestinal S. aureus colonization of
      patients at a large teaching hospital and determine the molecular characteristics
      of the identified strains. The second objective of this research was to determine
      risk factors associated with S. aureus intestinal colonization. Methods: A cross
      sectional study of 781 specimens from inpatients and outpatients at the
      University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory was
      conducted. S. aureus was identified using traditional culture methodologies.
      Methicillin-resistance was determined via PCR of the mecA gene. PVL PCR, spa
      typing, and antimicrobial sensitivity testing were also done. A nested case
      control study was done on a subset of patients with all colonized patients
      defined as cases and non-colonized controls. Medical record abstractions were
      done to identify risk factors for intestinal colonization in the nested study.
      Results: Out of 625 patients included in the final study, 58 were positive for S.
      aureus (9.3%). One isolate was positive for the PVL gene. A high number of
      isolates were resistant to multiple antibiotics including oxacillin (43.1%),
      erythromycin (51.7%), and levofloxacin (41.4%). All isolates were susceptible to
      vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin. In the nested
      study, having a disease or condition of the gastrointestinal tract significantly
      increased the odds of intestinal colonization (OR: 1.96, 95% CI: 1.04-3.7; aOR:
      13.9, 95% CI: 1.67-115.7). No other variables were significantly associated with
      increased odds of colonization. Conclusions: S. aureus was identified from the
      stool of patients at the University of Iowa Hospitals and Clinics, with a large
      number of those isolates being resistant to antibiotics and may serve a reservoir
      for subsequent infections as well as asymptomatic transmission.

PMID- 29568516
TI  - Development of a patient-centred intervention to improve knowledge and
      understanding of antibiotic therapy in secondary care.
AB  - Background: We developed a personalised antimicrobial information module co
      designed with patients. This study aimed to evaluate the potential impact of this
      patient-centred intervention on short-term knowledge and understanding of
      antimicrobial therapy in secondary care. Methods: Thirty previous patients who
      had received antibiotics in hospital within 12 months were recruited to co-design
      an intervention to promote patient engagement with infection management. Two
      workshops, containing five focus-groups were held. These were audio-recorded.
      Data were analysed using a thematic framework developed deductively based on
      previous work. Line-by-line coding was performed with new themes added to the
      framework by two researchers. This was used to inform the development of a
      patient information module, embedded within an electronic decision support tool
      (CDSS).The intervention was piloted over a four-week period at Imperial College
      Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires
      were developed and implemented to assess short term changes in patient knowledge
      and understanding and provide feedback on the intervention. Data were analysed
      using SPSS and NVIVO software. Results: Within the workshops, there was
      consistency in identified themes. The participants agreed upon and co-designed a
      personalised PDF document that could be integrated into an electronic CDSS to be
      used by healthcare professionals at the point-of-care. Their aim for the tool was
      to provide individualised practical information, signpost to reputable
      information sources, and enhance communication between patients and healthcare
      professionals.Eighteen out of thirty in-patients consented to participant in the
      pilot evaluation with 15/18(83%) completing the study. Median (range) age was
      66(22-85) years. The majority were male (10/15;66%). Pre-intervention, patients
      reported desiring further information regarding their infections and antibiotic
      therapy, including side effects of treatment. Deployment of the intervention
      improved short term knowledge and understanding of individuals infections and
      antibiotic management with median (IQR) scores improving from 3(2-5)/13 to 10(6
      11)/13. 13/15(87%) reported that they would use the intervention again.
      Conclusion: A personalised, patient-centred intervention improved understanding
      and short-term knowledge of infections and antibiotic therapy in participating
      patients'. Long term impact on attitudes and behaviours post discharge will be
      further investigated.

PMID- 29568517
TI  - Surfen and oxalyl surfen decrease tau hyperphosphorylation and mitigate neuron
      deficits in vivo in a zebrafish model of tauopathy.
AB  - Background: Tauopathies comprise a family of neurodegenerative disorders
      including Alzheimer's disease for which there is an urgent and unmet need for
      disease-modifying treatments. Tauopathies are characterized by pathological tau
      hyperphosphorylation, which has been shown to correlate tightly with disease
      progression and memory loss in patients suffering from Alzheimer's disease. We
      recently demonstrated an essential requirement for 3-O-sulfated heparan sulfate
      in pathological tau hyperphosphorylation in zebrafish, a prominent model organism
      for human drug discovery. Here, we investigated whether in vivo treatment with
      surfen or its derivatives oxalyl surfen and hemisurfen, small molecules with
      heparan sulfate antagonist properties, could mitigate tau hyperphosphorylation
      and neuronal deficits in a zebrafish model of tauopathies. Results: In vivo
      treatment of Tg[HuC::hTauP301L; DsRed] embryos for 2 days with surfen or oxalyl
      surfen significantly reduced the accumulation of the pThr181 tau phospho-epitope
      measured by ELISA by 30% and 51%, respectively. Western blot analysis also showed
      a significant decrease of pThr181 and pSer396/pSer404 in embryos treated with
      surfen or oxalyl surfen. Immunohistochemical analysis further confirmed that
      treatment with surfen or oxalyl surfen significantly decreased the AT8 tau
      epitope in spinal motoneurons. In addition, in vivo treatment of
      Tg[HuC::hTauP301L; DsRed] embryos with surfen or oxalyl surfen significantly
      rescued spinal motoneuron axon-branching defects and, as a likely consequence,
      the impaired stereotypical touch-evoked escape response. Importantly, treatment
      with hemisurfen, a surfen derivative devoid of heparan sulfate antagonist
      activity, does not affect tau hyperphosphorylation, nor neuronal or behavioural
      deficits in Tg[HuC::hTauP301L; DsRed] embryos. Conclusion: Our findings
      demonstrate for the first time that surfen, a well-tolerated molecule in clinical
      settings, and its derivative, oxalyl surfen, could mitigate or delay neuronal
      defects in tauopathies, including Alzheimer's disease.

PMID- 29568518
TI  - Exercise-induced increase in brain-derived neurotrophic factor in human
      Parkinson's disease: a systematic review and meta-analysis.
AB  - Background: Animal models of exercise and Parkinson's disease (PD) have found
      that the physiologic use of exercise may interact with the neurodegenerative
      disease process, likely mediated by brain derived neurotrophic factor (BDNF). No
      reviews so far have assessed the methodologic quality of available intervention
      studies or have bundled the effect sizes of individual studies on exercise
      induced effects on BDNF blood levels in human PD. Research design and methods: We
      searched MEDLINE, EMBASE, Cochrane Library, PsycINFO and PubMed from inception to
      June 2017. Results: Data aggregated from two randomized controlled trials and
      four pre-experimental studies with a total of 100 ambulatory patients with
      idiopathic PD (Hoehn/Yahr <=3) found improvements in BDNF blood concentration
      levels in all 6 studies (two RCTs and 4 pre-experimental studies). Pooled BDNF
      level change scores from the 2 RCTs resulted in a significant homogeneous summary
      effect size (Standardized Mean Difference 2.06, 95% CI 1.36 to 2.76), and a
      significant heterogeneous SES for the motor part of the UPDRS-III examination (MD
      -5.53, 95% CI -10.42 to -0.64). Clinical improvements were noted in all studies
      using a variety of outcome measures. Limitations: The evidence-base consists
      primarily of small studies with low to moderate methodological quality.
      Conclusions: This review provides preliminary evidence for the effectiveness of
      physical exercise treatments for persons with PD on BDNF blood levels. Further
      research is needed.

PMID- 29568519
TI  - Late open conversion after endovascular repair of abdominal aneurysm failure:
      Better and easier option than complex endovascular treatment.
AB  - Aim: Conversion to open repair becomes the last option in case of endovascular
      repair of abdominal aneurysm failure, when radiological interventional procedures
      are unfeasible. While early conversion to open repair generally derives from
      technical errors, aetiopathogenesis and results of late conversion to open repair
      often remain unclear. Methods: We report data from our Institute's experience on
      late conversion to open repair. Twenty-two late conversion to open repairs out of
      435 consecutive patients treated during a 18 years period, plus two endovascular
      repair of abdominal aneurysms performed in other centres, are analysed. The
      indication for conversion to open repair was aneurysm enlargement because of type
      I, type III, type II endoleak and endotension. Even if seven cases (23%) had
      shown an initial aneurysmal shrinkage, in a later phase, the sac began to enlarge
      again. In 12 patients, conversion to open repair was the last chance after
      unsuccessful secondary endovascular procedures. Results: Three cases (12.5%) were
      treated in emergency. Aortic cross-clamping was only infrarenal in 10 cases, only
      or temporarily suprarenal in 14 and temporarily supraceliac in 9 cases, for 19
      total and 5 partial endograft excisions. Two patients died for Multiple Organ
      Failure (MOF), on 42nd (endovascular repair of abdominal aneurysm infection) and
      66th postoperative day. No other conversion to open repair-related deaths or
      major complications were revealed by follow-up post-conversion to open repair
      (mean: 68 months ranging from 24 to 180 months). Conclusion: Late conversion to
      open repair is often an unpredictable event. It represents a technical challenge:
      specifically, the most critical point is the proximal aortic clamping that often
      temporarily excludes the renal circulation. In our series, conversion to open
      repair can be performed with a low rate of complications. In response to an
      endovascular repair of abdominal aneurysm failure, before applying complex
      procedures of endovascular treatment, conversion to open repair should be taken
      into account.

PMID- 29568520
TI  - Effects of chronic dexamethasone administration on hyperglycemia and insulin
      release in goats.
AB  - Background: Dexamethasone (Dex), a synthetic glucocorticoid, is among the most
      commonly used drugs worldwide in animals and humans as an anti-inflammatory and
      immunosuppressive agent. GC has profound effects on plasma glucose level and
      other metabolic conditions. However, the effect of prolonged use of Dex on
      glucose metabolism in ruminants is still unclear. Results: Ten goats were
      randomly assigned to two groups: the control goats were injected with saline, and
      the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg
      Dex. The results showed that plasma glucose and insulin concentrations were
      significantly increased after Dex administration (P < 0.05). Additionally, the
      content of hepatic glycogen was also markedly increased in Dex-treated goats (P <
      0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex
      (P > 0.05). The expression of several key genes, involved in blood glucose
      regulation, was detected by real-time PCR in the small intestine, skeletal muscle
      and liver. The expression of glucose transporter type 2 (GLUT2), sodium-glucose
      transporter 1 (SGLT1) and sodium-potassium ATPase (Na-K/ATPase) in the small
      intestine were generally increased by Dex, and GLUT2 mRNA expression was
      significantly up-regulated (P < 0.05). In liver, the expression of genes involved
      in gluconeogenesis including glucose-6-phosphatase catalytic subunit (G6PC),
      cytosolic form of phosphoenolpyruvate carboxykinase (PCK1) and pyruvate
      carboxylase (PC), were significantly down-regulated by Dex. However, the protein
      expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting
      a post-transcriptional regulation. In dorsal longissimus, the mRNA expression of
      genes associated with gluconeogenesis and the insulin signaling pathway were
      generally up-regulated by Dex, but the mRNA expression of two markers of muscle
      atrophy, namely F-box protein 32 (FBXO32/Atrogin1) and muscle RING-finger protein
      1 (MuRF1), was not altered by Dex. Conclusions: Taken together, these results
      indicate that chronic administration of a low dosage of Dex induces hyperglycemia
      mainly through gluconeogenesis activation in the goat liver.

PMID- 29568521
TI  - Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of
      dacarbazine in melanoma under obese state.
AB  - Background: Obesity is associated with increased risk, poor prognosis and outcome
      of therapy, in various cancers. Obesity-associated factors or adipokines,
      especially leptin and resistin, are purported to promote growth, survival,
      proliferation, and invasiveness of cancer cells. However, the mechanistic link
      between these adipokines and therapeutic response in malignancies is not clearly
      understood. Methods: ob/ob and db/db mouse models were used in this study to
      evaluate the role of leptin and resistin towards the outcome of dacarbazine
      (DTIC) therapy in melanoma. Unique in vitro approaches were employed to
      complement in vivo findings by culturing melanoma cells in the serum collected
      from the experimental mice. Results: Here, we have shown the role of important
      adipokines leptin and resistin in growth and the outcome of DTIC therapy in
      melanoma. Both leptin and resistin not only enhance proliferation of melanoma
      cells but also are involved in impairing the therapeutic efficacy of DTIC. Leptin
      and resistin treatment caused an increase in the protein levels of fatty acid
      synthase (FASN) and caveolin 1 (Cav-1) respectively, through their stabilization
      in A375 cells. Further, it was observed that leptin and resistin impaired the
      response of melanoma cells to DTIC via upregulation of heat shock protein 90
      (Hsp90) and P-glycoprotein (P-gp) respectively. Conclusion: These findings
      unraveled the involvement of adipokines (leptin and resistin) in melanoma
      progression, and more importantly, in the outcome of DTIC therapy.

PMID- 29568522
TI  - Association of sleep quality with excessive daytime somnolence and quality of
      life of elderlies of community.
AB  - Background: The progressive increase in the elderly population contributes to the
      fact that studies on human aging have important attention of health professionals
      and government agents, since they present a great challenge regarding public
      health. Our objective is to characterize the profile of older people with poor
      sleep quality and analyze possible associations with excessive daytime
      somnolence, quality of life and functional mobility. Methods: This is a cross
      sectional descriptive study, involving elderlies of the community, with the
      questionnaires Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale,
      WHOQOL-OLD and application of the Timed Up and Go test - TUG. Descriptive
      statistics, Student's t test for paired samples and Pearson's correlation
      coefficient (p <= 0.05) were used. Results: We recruited 131 elderly people,
      predominantly female (87%); mean age 68 +/- 7 years, low per capita income (84.8%
      <= 2 minimum wage), low education (86.3% <= 3 years of study), and mostly staying
      with relatives (67.9%), married (39.7%) or amassed (35.9%). Seventy-one percent
      of the sample is above normal weight, 90.1% of women have an abdominal
      circumference >= 80 cm and a high prevalence of chronic and psychosocial diseases
      was identified in the self-report, and the risk of obstructive sleep apnea in
      38.2%. The mean PSQI, Epworth Sleepiness Scale, WHOQOL-OLD and TUG were equal to,
      respectively, 11.2 +/- 3.2; 8.32 +/- 2.2; 84.8 +/- 10.2 and 8.97 +/- 2. An
      association of sleep quality with excessive daytime somnolence and quality of
      life, while not with functional mobility, was observed. Conclusion: The results
      of the present study allowed to identify a sleep quality associated with
      excessive daytime somnolence and quality of life and also to characterize the
      profile of elders with poor sleep quality.

PMID- 29568523
TI  - Blood microvasculature and lymphatic densities in endometrial polyps and adjacent
      and distant endometrium.
AB  - Objective: Endometrial polyps are localised growths of endometrial tissue
      containing glands, stroma and blood vessels, covered with epithelium. The
      reported prevalence of endometrial polyps is dependent upon the population being
      studied and the uterine imaging technique utilised. The light microscopy
      literature provides very little information regarding their microvasculature and
      lymphatic systems; however, a plethora of ultrasound data demonstrating single
      central arteries in most medium- or large-sized endometrial polyps are well
      documented. Methods: Archived formalin-fixed paraffin-embedded blocks of
      endometrial curettings were retrieved from files for women with confirmed
      endometrial polyps (n = 20) and women with normal endometrium (control
      endometrium; n = 32). Immunohistochemistry was performed with the antibodies CD31
      (blood vessels) and D2-40 (lymphatics). Blood vessels and lymphatics were
      quantified in endometrial polyps and adjacent, distant and control endometrium.
      Results: CD31 and D2-40 staining was present in all specimens, although there
      were no significant differences in blood vessel (F(3,70) = 2.36, p = 0.079) and
      lymphatic (F(3,70) = 0.16, p = 0.920) densities between endometrial polyps as
      well as adjacent, distant and control endometrium. There were also no significant
      differences in women with endometrial polyp-associated bleeding and those with no
      bleeding. In relation to infertility, there were no significant differences found
      in blood and lymphatic densities between women with endometrial polyps who were
      infertile and those with endometrial polyps who were fertile. Conclusion: Small
      blood vessel wall and perivascular structures rather than the distribution of
      vessels may be associated with abnormal bleeding.

PMID- 29568525
TI  - Two patients with rare mixed adenoneuroendocrine carcinomas of the rectum.
AB  - Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract are until
      today poorly understood and thus very challenging for interdisciplinary therapy.
      We herewith report the first case series of patients with a primary mixed
      adenoneuroendocrine carcinoma of the rectum. Both cases were initially diagnosed
      as adenocarcinoma and only secondarily with mixed adenoneuroendocrine carcinoma
      and had a poor outcome due to a rapid tumor progression and resistance to
      chemotherapy. A 65-year-old female presented with local tumor recurrence and
      hepatopulmonary metastasis 1 year after primary surgery for adenocarcinoma of the
      rectum and consecutive radiochemotherapy regimen. Fluorouracil (5-FU) was
      followed by bevacizumab- and capecitabine-based chemotherapy but had to be
      discontinued due to side effects and progressive disease. Progressive local pain
      syndrome accompanied by recurrent bleeding episodes led to a local tumor
      debulking operation. Afterward, mixed adenoneuroendocrine carcinoma as the
      underlying diagnosis in the final histopathological examination was detected. The
      patient died 3 months after the operation in the context of a fulminant tumor
      progress. A 63-year-old male patient underwent neoadjuvant radiochemotherapy and
      laparoscopic rectum resection. After 5 months, postoperative
      oxaliplatin/capecitabine-based adjuvant chemotherapy was switched to
      carboplatin/etopsid due to a progressive polyneuropathy and biopsy-proven
      pulmonary metastasis. The patient then had to be switched to local radiation of
      cerebral metastases and Topotecan due to cerebral bleeding episodes but died 18
      months after the initial diagnosis. In conclusion of our case series, mixed
      adenoneuroendocrine carcinomas of the rectum should be considered as a rare but
      aggressive tumor entity. An early and detailed histopathological diagnosis is
      required in order to establish an individual interdisciplinary treatment concept.

PMID- 29568524
TI  - Novel therapeutic strategies for degenerative disc disease: Review of cell
      biology and intervertebral disc cell therapy.
AB  - Intervertebral disc degeneration is a disease of the discs connecting adjoining
      vertebrae in which structural damage leads to loss of disc integrity.
      Degeneration of the disc can be a normal process of ageing, but can also be
      precipitated by other factors. Literature has made substantial progress in
      understanding the biological basis of intervertebral disc, which is reviewed
      here. Current medical and surgical management strategies have shortcomings that
      do not lend promise to be effective solutions in the coming years. With advances
      in understanding the cell biology and characteristics of the intervertebral disc
      at the molecular and cellular level that have been made, alternative strategies
      for addressing disc pathology can be discovered. A brief overview of the
      anatomic, cellular, and molecular structure of the intervertebral disc is
      provided as well as cellular and molecular pathophysiology surrounding
      intervertebral disc degeneration. Potential therapeutic strategies involving stem
      cell, protein, and genetic therapy for intervertebral disc degeneration are
      further discussed.

PMID- 29568526
TI  - Erythrocyte fatty acid profiles in children are not predictive of autism spectrum
      disorder status: a case control study.
AB  - Biomarkers promise biomolecular explanations as well as reliable diagnostics,
      stratification, and treatment strategies that have the potential to help mitigate
      the effects of disorders. While no reliable biomarker has yet been found for
      autism spectrum disorder (ASD), fatty acids have been investigated as potential
      biomarkers because of their association with brain development and neural
      functions. However, the ability of fatty acids to classify individuals with ASD
      from age/gender-matched neurotypical (NEU) peers has largely been ignored in
      favor of investigating population-level differences. Contrary to existing work,
      this classification task between ASD and NEU cohorts is the main focus of this
      work. The data presented herein suggest that fatty acids do not allow for
      classification at the individual level.

PMID- 29568527
TI  - Leukadherin-1 ameliorates endothelial barrier damage mediated by neutrophils from
      critically ill patients.
AB  - Background: Multi-organ failure occurs during critical illness and is mediated in
      part by destructive neutrophil-to-endothelial interactions. The beta2 integrin
      receptor, CR3 (complement receptor 3; Mac-1; CD11b/CD18), which binds endothelial
      intercellular adhesion molecule-1 (ICAM-1), plays a key role in promoting the
      adhesion of activated neutrophils to inflamed endothelia which, when prolonged
      and excessive, can cause vascular damage. Leukadherin-1 (LA-1) is a small
      molecule allosteric activator of CR3 and has been shown to promote adhesion of
      blood neutrophils to inflamed endothelium and restrict tissue infiltration.
      Therefore, LA-1 offers a novel mechanism of anti-inflammatory action by
      activation, rather than inhibition, of the neutrophil CR3 integrin. However,
      whether promotion of neutrophil-to-endothelial interaction by this novel
      therapeutic is of benefit or detriment to endothelial barrier function is not
      known. Methods: Critically ill septic and trauma patients were prospectively
      enrolled from the surgical and the trauma ICU. Blood was collected from these
      patients and healthy volunteers. Neutrophils were isolated by dextran
      sedimentation and adhered to TNF-alpha (tumor necrosis factor-alpha)-activated
      human umbilical vein endothelial (HUVEC) monolayers in the presence or absence of
      fMLP (formylmethionine-leucine-phenylalanine) and/or LA-1. Electric cell
      substrate impedance sensing (ECIS) and exposure of underlying collagen were used
      to quantify endothelial barrier function and permeability. Results: Neutrophils
      from critically ill trauma and septic patients caused similar degrees of
      endothelial barrier disruption which exceeded that caused by cells obtained from
      healthy controls both kinetically and quantitatively. LA-1 protected barrier
      function in the absence and presence of fMLP which served as a secondary
      stimulant to cause maximal loss of barrier function. LA-1 protection was also
      observed by quantifying collagen exposure underlying endothelial cells challenged
      with fMLP-stimulated neutrophils. LA-1 treatment resulted in decreased migration
      dynamics of neutrophils crawling on an endothelial monolayer with reduced speed
      (MUm/s = 0.25 +/- 0.01 vs. 0.06 +/- 0.01, p < 0.05), path length (MUm = 199.5 +/-
      14.3 vs. 42.1 +/- 13.0, p < 0.05), and displacement (MUm = 65.2 +/- 4.7 vs. 10.4
      +/- 1.3; p < 0.05). Conclusion: Neutrophils from patients with trauma or sepsis
      cause endothelial barrier disruption to a similar extent relative to each other.
      The CR3 agonist LA-1 protects endothelial barrier function from damage caused by
      neutrophils obtained from both populations of critically ill patients even when
      exposed to secondary stimulation.

PMID- 29568529
TI  - Prevalence of anemia before and after initiation of antiretroviral therapy among
      HIV infected patients at Black Lion Specialized Hospital, Addis Ababa, Ethiopia:
      a cross sectional study.
AB  - Background: Anemia is the most common hematological abnormality in Human
      immunodeficiency virus (HIV) positive patients and a significant predictor of its
      progression to AIDS or death. This study was aimed to assess the prevalence of
      anemia before and after initiation of antiretroviral therapy (ART) among HIV
      positive patients attending Black Lion Specialized Hospital, Addis Ababa,
      Ethiopia. Methods: A cross sectional study was conducted from January to April,
      2017 in Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A total of 255
      patients on ART were selected using simple random sampling techniques. Socio
      demographic and clinical characteristics of the study subjects were collected
      using structured questionnaire. Measurements of complete blood cell counts and
      CD4 + T cell counts were made using Sysmex XT 2000i hematology analyzer and BD
      FACS Count CD4 analyzer, respectively. Statistical analysis of the data (Chi
      square, paired T-test, logistic regression) was done using SPSS version 20. A p
      value < 0.05 was considered as significant. Results: Prevalence of anemia before
      and after ART initiation was 41.9 and 11.4% respectively. There are a
      significance differences in CD4 + T cell count, RBC count, hemoglobin values and
      RBC indices in HIV patients before and after ART initiation (p-value < 0.05). WHO
      clinical stages and CD4+ T cell counts were found to be associated with the
      prevalence of anemia before ART initiation. Among the total number of anemic
      cases, normocytic normochromic anemia was present in 71% of the cases before ART
      and in 58.6% of the cases after ART. The prevalence of macrocytic normochromic
      anemia before and after ART initiation was 4.7 and 27.6% respectively.
      Conclusions: It is evident from this study that there is a remarkable reduction
      in the prevalence of anemia after ART initiation. However, a significant
      proportion of HIV patients remained anemic after 6 months of ART initiation
      suggesting the need for routine screening and proper treatment of anemia to
      mitigate its adverse effects.

PMID- 29568528
TI  - Achieving the earliest possible reperfusion in patients with acute coronary
      syndrome: a current overview.
AB  - Acute coronary syndrome (ACS) remains one of the leading causes of mortality
      worldwide. Appropriate management of ACS will lead to a lower incidence of
      cardiac arrest. Percutaneous coronary intervention (PCI) is the first-line
      treatment for patients with ACS. PCI techniques have become established. Thus,
      the establishment of a system of health care in the prehospital and emergency
      department settings is needed to reduce mortality in patients with ACS. In this
      review, evidence on how to achieve earlier diagnosis, therapeutic intervention,
      and decision to reperfuse with a focus on the prehospital and emergency
      department settings is systematically summarized. The purpose of this review is
      to generate current, evidence-based consensus on scientific and treatment
      recommendations for health care providers who are the initial points of contact
      for patients with signs and symptoms suggestive of ACS.

PMID- 29568531
TI  - Mycobacterium kansasii osteomyelitis - a masquerading disease.
AB  - Introduction: Non-tuberculous mycobacteria (NTM) are environmental bacteria
      capable of causing an opportunistic myriad of infections. Mycobacterium kansasii,
      one such NTM, is responsible for causing pulmonary disease in immunocompromised
      patients. Rare extrapulmonary manifestations such as lymphadenitis,
      osteoarticular manifestations, and skin and soft tissue infections are also
      observed. Case presentation: Here, we report an unusual case of sternoclavicular
      joint and elbow joint infection with M. kansasii in a relatively immunocompetent
      patient. Histopathology did not show classic granulomas and mycobacterial
      infection was not initially considered as a possibility. However repeat biopsies
      were sent for mycobacterial cultures which then grew M. kansasii. Conclusion:
      Diagnosis of M. kansasii in such cases can be difficult and culture-positive
      results may not necessarily imply positive diagnosis as they can be environmental
      contaminants. Furthermore, M. kansasii can cause infections without the
      characteristic granuloma formation, which can further complicate tissue
      diagnosis. This underlines the importance of ensuring that tissue samples
      obtained are cultured for mycobacteria.

PMID- 29568530
TI  - A case of Wohlfahrtiimonas chitiniclastica bacteremia in continental United
      States.
AB  - Introduction: Wohlfahrtiimonas chitiniclastica has been associated with open
      wound infections, cellulitis, osteomyelitis, and bacteremia. Case presentation:
      We report the case of a 41 year old woman with history of congenital
      myelomeningocele, paraplegia and extensive decubitus ulcers that developed W.
      chitiniclastica bacteremia secondary to an infected ulcer. Conclusion: W.
      chitiniclastica is an emerging human pathogen that can be readily identified by
      MALDI-TOF or sequencing.

PMID- 29568532
TI  - First case report of sepsis caused by Rhizobium pusense in Japan.
AB  - Introduction: Species of the genus Rhizobium are opportunistic, usually
      saprophytic, glucose-non-fermenting, Gram-negative bacilli found in agricultural
      soil. Rhizobium pusense infections are the least common Rhizobium infections and
      have low incidence. Case presentation: Herein, we report the first case of sepsis
      with R. pusense in Japan in a 67-year-old Japanese woman with a history of
      hyperlipidaemia, hypertension, diabetes, hypothyroidism and osteoporosis. She had
      undergone cerebrovascular treatment because she was diagnosed with a subarachnoid
      haemorrhage. The results of postoperative blood culture showed oxidase-positive,
      urease-positive, non-lactose-fermenting Gram-stain-negative rods. Using the
      Vitek2 system, the isolate was distinctly identified as Rhizobium radiobacter.
      However, 16S rRNA gene sequencing showed 99.93 % similarity with the type strain
      of R. pusense and 99.06 % similarity with the type strain of R. radiobacter.
      Additional gene sequencing analysis using recA (97.2 %) and atpD (96.2 %) also
      showed that the isolated strain is most closely related to R. pusense. The
      patient was cured by treatment using intravenous meropenem (3 g/d) for 4 weeks
      and was discharged safely. Conclusion: The definite source of sepsis was unknown.
      However, the possibility of having been infected through the catheter during the
      cerebrovascular operation was speculated.

PMID- 29568533
TI  - First confirmed case of nasal pythiosis in a horse in Thailand.
AB  - Introduction: Pythiosis is caused by Pythium insidiosum, a fungus-like organism
      in the class Oomycetes. It can infect humans and a variety of animal species in
      tropical, subtropical and some temperate regions. Cases of animal pythiosis have
      occurred predominantly in horses in the skin and subcutaneous tissue at the limbs
      and in the ventral portion of thoracoabdominal wall - lesions in the nasal region
      are rarely reported. Moreover, although many human pythiosis cases have been
      reported in Thailand, no cases of animal pythiosis in Thailand have been
      reported. Case presentation: We report a case of pythiosis in a horse infected at
      the nasal cavity. Diagnosis was performed by zoospore formation by bait
      technique, immunohistochemical stain, immunochromatography and sequence analysis.
      Conclusion: The sequences of rDNA were 99 % and 96 to 99 % identical to GenBank
      isolates of Pythium insidiosum from two Thai human patients and horses from
      various countries, respectively. This represents the first confirmed report of
      nasal equine pythiosis in Thailand.

PMID- 29568534
TI  - Ignavigranum ruoffiae, a rare pathogen that caused a skin abscess.
AB  - Introduction: Ignavigranum ruoffiae is an extremely rare cause of human
      infections. Case presentation: An 83-year-old male with a painless, ten-day-old,
      erythematous skin abscess on his left flank, which had showed a purulent
      discharge for 48 h, was admitted to the Emergency service. He was treated with
      cephalexin, disinfection with Codex water and spray of rifampicin. Five days
      later, surgical drainage of the abscess was proposed due to the torpid evolution
      of the patient. Samples were taken for culture, and antibiotic treatment with
      trimethoprim-sulfamethoxazole was established. The patient returned after 10 days
      showing healing of the abscess. Microbiological studies showed a few Gram
      positive cocci present as single cells and short chains that grew after 72 h of
      incubation at 35  degrees C with CO2 on 5 % sheep blood agar. Colonies presented
      a strong sauerkraut odour. Initial biochemical test results were negative for
      catalase, aesculin and bile-aesculin, and positive for pyrrolidonyl arylamidase,
      leucine aminopeptidase and growth in 6.5 % NaCl broth, which prompted the
      preliminary identification of Facklamia species or I. ruoffiae. The positive
      result for arginine deamination and negative result for hippurate hydrolysis,
      failure to produce acid from mannitol, sucrose, sorbitol or trehalose, plus the
      distinctive sauerkraut odour identified the organism as I. ruoffiae. The
      phenotypic identification was confirmed by 16S rRNA gene sequence analysis. The
      strain seemed to be susceptible to the antimicrobials tested but had decreased
      susceptibility to carbapenems. Conclusion: This case provides more insights into
      the phenotypic characteristics and antimicrobial resistance profile of I.
      ruoffiae.

PMID- 29568535
TI  - An operating room employee with a necrotic fingertip.

PMID- 29568536
TI  - Cerebellar cognitive affective syndrome: insights from Joubert syndrome.
AB  - Background: Joubert syndrome (JS) is a rare, autosomal recessively inherited
      genetic disorder characterized morphologically by unique developmental
      malformations of the cerebellum and brainstem (the molar tooth sign), and
      clinically by impaired motor functions and intellectual disability. Patients with
      JS often face multiple cognitive challenges, but the neuropsychological profile
      of this condition has not been well characterized. Methods: We performed
      comprehensive neurological and neuropsychological evaluations in three adult
      brothers with JS, ages 32, 27, and 25 years. Results: They all exhibited impaired
      motor control, global developmental delay most evident in executive function,
      affect regulation, and social skill set, and similar patterns of neuropsychiatric
      symptoms. Conclusions: These findings provide new insights into the intellectual
      and neurobehavioral phenotype of JS, which we regard as a developmental form of
      the cerebellar cognitive affective / Schmahmann syndrome (CCAS). These
      observations have direct clinical relevance for the diagnosis and care of
      patients with JS, and they help further the understanding of the multiple
      manifestations of atypical cerebrocerebellar development.

PMID- 29568537
TI  - A Province-wide, Cross-sectional Study of Demographics and Medication Use of
      Patients in Hemodialysis Units Across Ontario.
AB  - Background: Hemodialysis patients are at an increased risk of polypharmacy as
      they have the highest pill burden of all chronically ill patient populations,
      with an estimated average of 12 medications per day. Objectives: The aim of this
      study was to evaluate prescribing patterns of outpatient medications in patients
      receiving in-center hemodialysis. This was done to identify potential candidate
      medications for future quality improvement initiations to optimize prescribing.
      Design: We conducted a descriptive retrospective cross-sectional study in the
      province of Ontario, Canada, using several linked health care databases housed at
      the Institute for Clinical Evaluative Sciences (ICES). Setting: We considered
      outpatient medications dispensed to patients eligible for the Ontario Drug
      Benefit program. Patients: Patients were receiving chronic in-center hemodialysis
      at one of the 69 facilities in the province of Ontario, Canada as of October 1,
      2013. Measurements: We assessed whether any of our 28 study medications of
      interest were recently dispensed (within the prior 120 days), the type of
      prescribing physician, and the associated medication costs. The 28 included
      medications of interest (ie, proton pump inhibitors, benzodiazepines) were
      selected because they may not have a true indication for dialysis patients and/or
      there are safety concerns with their use in this population. Results are
      presented as median (25th, 75th percentile). Methods: We conducted this study at
      ICES according to a prespecified protocol approved by the Research Ethics Board
      at Sunnybrook Health Sciences Centre (Toronto, Ontario). Results: A total of 3094
      patients on chronic in-center hemodialysis received a study drug of interest
      (age: 76.5 years [SD: 7.3]), 44% women). Patients were dispensed 11 (8, 14)
      unique medication products with more than two-thirds of patients dispensed 9 or
      more different medications. The median number of annual health care visits was 7
      (3-15) with more than half the cohort receiving prescriptions from 3 or more
      specialists. The 10 most commonly dispensed study medications cost more than 3
      million dollars in direct costs in 1 year. Limitations: Our study was also
      subjected to some limitations of health care databases. Conclusions: Polypharmacy
      is frequent in in-center hemodialysis patients. To decrease polypharmacy and its
      associated negative outcomes, health care providers need to implement tools to
      optimize medication use and deprescribe medications that lack evidence for
      efficacy and safety in hemodialysis patients. Therefore, strategies to improve
      prescribing and discontinue ineffective medications warrant testing for better
      patient outcomes and reduced health care costs.

PMID- 29568538
TI  - Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in
      allergic asthmatic mice.
AB  - Background: Asthma is a worldwide common chronic airway disease that cannot be
      cured and results in the huge burden in public health. Oxidative stress was
      considered an important mechanism in the pathogenesis of asthma. Hydrogen gas
      been demonstrated to function as a novel antioxidant and exert therapeutic
      antioxidant activity in a number of diseases and the function of this nontoxic
      gas in asthma was unclear. The purpose of the study aims to examine the effect of
      inhalation hydrogen gas on the pathophysiology of a mouse model of asthma.
      Methods: A murine model of ovalbumin (OVA)-induced allergic airway inflammation
      was used in this study. Briefly, Mice were sensitized to ovalbumin and received
      inhalation of 67% high concentration of hydrogen gas for 60 min once a day for 7
      consecutive days after OVA or PBS challenge respectively. Lung function was
      assessed in the apparatus with 4 channels of biological signal system. Morphology
      and goblet cell hyperplasia were stained by H/E and Periodic acid-Schiff
      staining. Cytologic classification in the bronchial alveolar lavage fluid (BALF)
      was analyzed by Wright Giemsa staining. Serum, BALF and lung tissue were
      collected for biochemical assay. One-way analysis of variance (ANOVA) was used to
      determine statistical significance between groups. Multiple comparisons were made
      by Bonferroni's Multiple Comparison Test by using GraphPad Prism 5 software.
      Results: Inhalation of hydrogen gas abrogated ovalbumin-induced the increase in
      lung resistance. Concomitantly, the asthmatic mice showed severe inflammatory
      infiltration and goblet cell hyperplasia which were reversed by hydrogen gas
      inhalation. Hydrogen gas inhalation reduced significantly the number of total
      cells, eosinophils and lymphocytes in BALF. Increased level of IL-4, IL-13, TNF
      alpha and CXCL15 in the BALF and IL-4 in the serum were decreased significantly
      after inhalation. Hydrogen gas inhalation markedly upregulated the activity of
      decreased superoxide dismutase and significantly attenuated the increased level
      of malondialdehyde and myeloperoxidase. Conclusions: Hydrogen gas inhalation
      improves lung function and protects established airway inflammation in the
      allergic asthmatic mice model which may be associated with the inhibition of
      oxidative stress process. This study provides a potential alternative therapeutic
      opportunity for the clinical management of asthma.

PMID- 29568539
TI  - Low level of knowledge about neonatal danger signs and its associated factors
      among postnatal mothers attending at Woldia general hospital, Ethiopia.
AB  - Background: Neonatal mortality has persisted high in Ethiopia in spite of many
      efforts being applied to decrease this adverse trend. Early detection of neonatal
      illness is an important step towards improving newborn survival. Toward this end,
      there is a need for the mothers to be able to identify signs in neonates that
      signify severe illnesses. The aim of this study was to assess knowledge about
      neonatal danger signs and its associated factors among postnatal mothers
      attending at Woldia general hospital, Ethiopian. Methods: Institutional based
      cross-sectional study design was conducted from January-May, 2017. The hospital
      that provides antenatal care (ANC), delivery, and postnatal services was
      purposively sampled. Structured interviewer managed questionnaire was
      administered to postnatal mothers attending Woldia general hospital. Frequencies,
      bivariate and multivariate logistic regression were determined using the SPSS
      software (Version 20). Results: During the study period 197 mothers attending
      postnatal care (PNC) service at Woldia general hospital were interviewed.
      Information on different neonatal danger signs was not provided to 92(46.7%)
      postnatal mothers during their antenatal clinic attendance by the healthcare
      providers. The majority of mothers, 174(88.3%) identified less than six neonatal
      danger signs. The hotness of the body of neonates was the commonly recognized
      danger sign by 106(53.8%) postnatal mothers. Of the total mothers, 67(34%),
      60(30.5%), 56(28.4%), 44(22.3%) recognized unable to breastfeeding, convulsion,
      lethargy, difficulty in breathing as newly born danger signs, respectively. Out
      of 197 mothers, 32(16.2%) were giving birth at home. Mother's age(AOR = 1.33, 95%
      CI: 1.99-3.08), marital status(AOR = 2.50, 95% CI: 0.29-4.31), mother's education
      status(AOR = 3.48, 95% CI:1.57-8.72), husband's education(AOR = 4.92, 95% CI:
      1.29-12.81), attending ANC (AOR = 2.88, 95% CI: 1.15, 4.85), mother's
      residence(AOR = 0.78, 95% CI: 0.47-1.65), information about neonatal danger
      signs(AOR = 3.48, 95% CI 1.40-9.49) had positive association with maternal level
      of knowledge to identify different neonatal danger signs. Conclusion: Maternal
      knowledge level about neonatal danger signs was very low. Therefore, intervention
      modalities that focus on increasing level of parental education, access to ANC
      and PNC service are needed.

PMID- 29568540
TI  - Developmental changes of fluconazole clearance in neonates and infants in
      relation to ontogeny of glomerular filtration rate: literature review and data
      analysis.
AB  - Background: Fluconazole is frequently prescribed for the treatment of systemic
      fungal infection in neonates and infants. At present, prediction of fluconazole
      doses according to developmental changes in fluconazole clearance is not being
      done in these patients. We aimed to formulate a developmental model of
      fluconazole clearance taking into account the ontogeny of renal function, since
      the drug is largely eliminated renally. Methods: We systematically retrieved the
      data of fluconazole pharmacokinetics and renal function in children and adults
      from databases (MEDLINE and Japan Medical Abstracts Society). Datasets were
      retrieved from individual children or groups from 9 studies comprising 55
      neonates or infants at postmenstrual age (PMA) 27-58 weeks. Datasets were
      retrieved from 5 studies comprising 60 children and from 13 studies comprising
      152 adults. Datasets of glomerular filtration rate (GFR) for individual pediatric
      subjects were retrieved from 4 studies comprising 187 neonates or infants.
      Results: Fluconazole clearance normalized to body surface area (BSA) (CLBSA) in
      neonates was 1/3 to 1/4 of adult values, but CLBSA increased rapidly during the
      neonatal and infantile periods and attained near adult values at PMA 60 weeks. A
      significant correlation between CLBSA and PMA was observed in neonates and
      infants: CLBSA (mL/min/m2) = 0.26? PMA (weeks) - 4.9 (r = 0.68, p < 0.001). In
      addition, the developmental time course of GFR normalized to BSA (GFRBSA) was
      fitted well to a sigmoidal model with the maximum GFRBSA of 149 mL/min/1.73m2,
      PMA associated with 50% of GFRBSA,max (PMA50) of 54 weeks, and the Hill
      coefficient of 3.7. A significant correlation between fluconazole clearance and
      GFR was found in neonates and infants: CL (mL/min) = 0.34?GFR (mL/min) - 0.53 (r
      = 0.84, p < 0.001). Assuming that plasma drug concentrations required for
      treating fungal infection are comparable between children and adults, fluconazole
      doses for pediatric patients with given PMAs may be predicted from adult doses
      (such as 100 mg/day) using size-normalized clearance as a scaling factor. The
      predicted doses for neonates and infants were largely within the ranges
      recommended in the prescribing information. Conclusions: The present study
      indicates that fluconazole doses for neonates and infants may be predicted from
      developmental change of systemic clearance, the ontogeny of which parallels the
      maturation of nephron function.

PMID- 29568541
TI  - Prevalence of feline immunodeficiency virus and feline leukaemia virus infection
      in Malaysia: a retrospective study.
AB  - Objectives: Feline ownership is popular and represents the largest segment of the
      pet population in Malaysia. Most feline owners own, on average, 2-3 cats, with
      some having >10 cats per household. Feline immunodeficiency virus (FIV) and
      feline leukaemia virus (FeLV) are two clinically important viral infections in
      cats. Documenting the prevalence of these diseases in the feline population is
      important for both veterinarians and the public. Methods: This was a
      retrospective study, using data collected from the domestic cat population seen
      at a 24 h private veterinary hospital in Malaysia, to determine the prevalence of
      FIV and FeLV in an urban area and risk factors associated with these infections.
      Between 2010 and 2016, 2230 blood samples were collected and tested for FIV
      antibodies and FeLV antigen using commercially available ELISA test kits.
      Results: In total, 10.0% (n = 224; 95% confidence interval [CI] 8.80-11.26) were
      seropositive for FIV; 12.0% (n = 267; 95% CI 10.62-13.32) were seropositive for
      FeLV; and 2.6% (n = 58; 95% CI 2.01-3.17) were seropositive for both. Conclusions
      and relevance: The prevalence of FIV is lower and FeLV higher than previously
      documented for this region. Because of the immunosuppressive potential of both
      viruses, client education and use of appropriate control strategies such as
      routine screening, vaccination and eradication should be considered.

PMID- 29568542
TI  - Mammary fibroadenomatous hyperplasia in a male cat.
AB  - Case summary: Mammary fibroadenomatous hyperplasia (MFH) is a benign pathology
      characterised by extensive proliferation of the ductal epithelium and mammary
      stroma. It typically occurs in young female cats, and seems to result from
      hypersensitivity to progesterone. A 2-year-old entire male European Shorthair cat
      presented to the veterinary clinic with enlargement of several mammary glands,
      which had developed within the previous 10 days. There was no prior
      administration of progestin in the cat's medical history. Diagnostic tests were
      performed to assess the basal progesterone concentration and the concentration
      after stimulation with gonadotropin-releasing hormone, which ruled out the
      presence of functional ovarian tissue. Histological examination of the testes
      excluded hormone-secreting testicular tumours. Histological examination of the
      mammary gland confirmed the diagnosis of MFH. Treatment was started with
      aglepristone, a selective competitor for progesterone receptors, administered
      subcutaneously at 15 mg/kg at days 1, 2, 8 and 15. A reduction in the size of the
      mammary glands was evident 6 days after the first administration, with complete
      remission observed after 4 weeks. Relevance and novel information: To the best of
      our knowledge, this is the first full report of MFH in a male cat. Although the
      origin of the progestins responsible for MFH in this case could not be confirmed,
      in the light of the diagnostic tests performed and the results obtained,
      accidental contact with hormone-like substances seems to be the only plausible
      explanation for the cat's clinical signs. Inhibitor therapy was successful.

PMID- 29568544
TI  - No evidence of disease activity (NEDA) analysis by epochs in patients with
      relapsing multiple sclerosis treated with ocrelizumab vs interferon beta-1a.
AB  - Background: No evidence of disease activity (NEDA; defined as no 12-week
      confirmed disability progression, no protocol-defined relapses, no new/enlarging
      T2 lesions and no T1 gadolinium-enhancing lesions) using a fixed-study entry
      baseline is commonly used as a treatment outcome in multiple sclerosis (MS).
      Objective: The objective of this paper is to assess the effect of ocrelizumab on
      NEDA using re-baselining analysis, and the predictive value of NEDA status.
      Methods: NEDA was assessed in a modified intent-to-treat population (n = 1520)
      from the pooled OPERA I and OPERA II studies over various epochs in patients with
      relapsing MS receiving ocrelizumab (600 mg) or interferon beta-1a (IFN beta-1a;
      44 MUg). Results: NEDA was increased with ocrelizumab vs IFN beta-1a over 96
      weeks by 75% (p < 0.001), from Week 0-24 by 33% (p < 0.001) and from Week 24-96
      by 72% (p < 0.001). Among patients with disease activity during Weeks 0-24, 66.4%
      vs 24.3% achieved NEDA during Weeks 24-96 in the ocrelizumab and IFN beta-1a
      groups (relative increase: 177%; p < 0.001). Conclusion: Superior efficacy with
      ocrelizumab compared with IFN beta-1a was consistently seen in maintaining NEDA
      status in all epochs evaluated. By contrast with IFN beta-1a, the majority of
      patients with disease activity early in the study subsequently attained NEDA
      status with ocrelizumab.

PMID- 29568545
TI  - Knowledge, attitude and practice of medical laboratory practitioners in the fight
      against Ebola virus disease.
AB  - Introduction: Ebola virus disease (EVD) in West Africa was an enormous public
      health challenge. Nigeria was able to contain the spread of the virus with a
      concerted effort and an effective public health response in terms of
      identification of contacts, rapid laboratory diagnosis, quarantine and
      symptomatic treatment. We determined the knowledge, attitude and practice of
      medical laboratory practitioners (MLPs) in this post-Ebola epidemic era. Methods:
      This cross-sectional study was carried out in eight hospitals in Kano State for 6
      months, between January and June 2016. It involved medical laboratory scientists
      (MLS), medical laboratory technicians (MLT) and medical laboratory assistants
      (MLA). Questionnaires were administered and analysed. Results: Of the 75
      participants, mean knowledge score was 5.54 (standard deviation [SD] +/-1.44)
      while the mean attitude score was 13.72 +/-2.80, and mean practice score was 3.10
      +/-0.80. Mean age of participants was 36.82 +/- 8.07 years. There was full
      awareness of EVD among all 75 participants; however, many medical laboratory
      practitioners (52.7%) did not know EVD prevention methods. The majority (86.1%)
      knew the source of disease outbreak and most MLPs (66.7%) practised improper hand
      washing to prevent Ebola transmission. In addition, they had a negative attitude
      and practice towards EVD. Of 71 MLPs, 52 (73.2%) strongly disagreed that a
      traditional remedy was preferable in EVD treatment. Conclusion: Fear of EVD among
      MLPs has declined.

PMID- 29568546
TI  - Effect of calcium and vitamin D supplementation on bone mineral accrual among HIV
      infected Thai adolescents with low bone mineral density.
AB  - Background: The benefits of calcium and vitamin D supplementation for low bone
      mass remains controversial. This study assessed the changes in bone mineral
      density (BMD) during periods without and with calcium and vitamin D
      supplementation among HIV-infected adolescents with low BMD. Method: Perinatally
      HIV-infected Thai adolescents aged 12-20 years were enrolled into Phase 1 (pre
      supplementation) to evaluate longitudinal change of BMD. We provided education
      about appropriate dietary intake and exercise. Lumbar spine (L2-L4) BMD and
      vitamin D status (25-hydroxyvitamin D [25(OH)D]) were assessed at baseline and at
      12-24 month intervals. Participants with a BMD Z-score<=-2 were enrolled into
      Phase 2 (supplementation) that provided calcium 600 mg plus cholecalciferol 200
      IU twice daily for 6 months. BMD and 25(OH)D were re-assessed at the end of
      study. Results: Ninety-four participants were enrolled into the Phase 1. Median
      age (IQR) was 14.3 (13.0-15.5) years, with 67% at Tanner stage 3-5, 89% with a
      plasma HIV-1 RNA<50 copies/mL. During Phase 1 and a 22.7-month follow-up, median
      L2-L4 BMD Z-scores remained unchanged (-1.06 vs -1.08, P=0.08), but 25(OH)D
      levels increased (24.7 vs 26.7 ng/mL, P=0.01). Twenty-six (28%) adolescents had
      low BMD and were enrolled into Phase 2, with 24 (92%) completing follow-up. The
      median L2-L4 BMD Z-scores (-2.59 vs -1.70; P<0.001) and calcium level (9.3 vs 9.5
      mg/dL, P=0.04) significantly improved. There was an increase in BMD Z-scores
      during the 6-months post-supplementation as compared to the 21-month pre
      supplementation period (0.65 vs -0.50, P=0.03). Conclusion: HIV-infected
      adolescents with low BMD had improved bone health after calcium and vitamin D
      supplementation. A randomised controlled trial is warranted to confirm the
      benefits of these supplements.

PMID- 29568547
TI  - HIV rapid diagnostic testing by lay providers in a key population-led health
      service programme in Thailand.
AB  - Introduction: Rapid diagnostic testing (RDT) for HIV has a quick turn-around
      time, which increases the proportion of people testing who receive their result.
      HIV RDT in Thailand has traditionally been performed only by medical
      technologists (MTs), which is a barrier to its being scaled up. We evaluated the
      performance of HIV RDT conducted by trained lay providers who were members of, or
      worked closely with, a group of men who have sex with men (MSM) and with
      transgender women (TG) communities, and compared it to tests conducted by MTs.
      Methods: Lay providers received a 3-day intensive training course on how to
      perform a finger-prick blood collection and an HIV RDT as part of the Key
      Population-led Health Services (KPLHS) programme among MSM and TG. All the
      samples were tested by lay providers using Alere Determine HIV 1/2. HIV-reactive
      samples were confirmed by DoubleCheckGold Ultra HIV 1&2 and SD Bioline HIV 1/2.
      All HIV-positive and 10% of HIV-negative samples were re-tested by MTs using
      Serodia HIV 1/2. Results: Of 1680 finger-prick blood samples collected and tested
      using HIV RDT by lay providers in six drop-in centres in Bangkok, Chiang Mai,
      Chonburi and Songkhla, 252 (15%) were HIV-positive. MTs re-tested these HIV
      positive samples and 143 randomly selected HIV-negative samples with 100%
      concordant test results. Conclusion: Lay providers in Thailand can be trained and
      empowered to perform HIV RDT as they were found to achieve comparable results in
      sample testing with MTs. Based on the task-shifting concept, this rapid HIV
      testing performed by lay providers as part of the KPLHS programme has great
      potential to enhance HIV prevention and treatment programmes among key at-risk
      populations.

PMID- 29568548
TI  - Safety of lumbar puncture procedure in an international research setting during
      acute HIV infection.
AB  - Background: Cerebrospinal fluid (CSF) sampling at the time of acute HIV infection
      (AHI) is crucial in understanding NeuroAIDS pathogenesis. Here, we report on the
      safety of performing a lumbar puncture (LP) during untreated AHI and follow-up
      after initiation of combination antiretroviral therapy (cART). Methods: We
      reviewed clinical records of participants who took part in an AHI protocol in
      Bangkok, Thailand, including untreated AHI subjects (baseline), and longitudinal
      visits following immediate initiation of cART to assess rates and risk of post
      lumbar puncture headaches (PLPH). A cerebrospinal fluid (CSF) volume of 10-20 mL
      was collected using standard cutting-edge or atraumatic needles. Results: From
      April 2009 to February 2016, 195 LPs were performed, of which 89 (46%) were at
      baseline. The LP procedures at baseline were not associated with an additional
      PLPH risk as compared to repeat LPs after cART initiation (26/89 [29%] vs 4/27
      [15%], respectively; P=0.134). Higher body mass index (BMI) at baseline (P=0.070)
      and use of an atraumatic needle (P=0.058) had trend-level associations with
      reduced PLPH. A higher CSF volume collection (20 mL) was independently associated
      with a lower PLPH frequency (P=0.024). This association was similar in a subgroup
      analysis with the use of atraumatic needles. The CD4+ T lymphocyte count, blood
      and CSF HIV viral load, Fiebig staging, and the presence of an acute retroviral
      syndrome did not correlate with risk for PLPH (all P>0.05). Conclusion: The
      frequency of PLPH during AHI was similar to that seen in the setting of cART
      treated HIV infection and not higher with a larger CSF volume collection. Our
      study adds to the existing evidence that atraumatic needles should be used to
      minimise the risk of PLPH.

PMID- 29568549
TI  - Markers of subclinical atherosclerotic disease in HIV-infected individuals.
AB  - Background: Wider access to antiretroviral treatment (ART) has resulted in a
      decline in the number of people dying due to AIDS-related causes. However, with
      this increased longevity, accelerated rates of cardiovascular and atherosclerotic
      diseases are on the rise. We hypothesised that the prevalence of atherosclerotic
      cardiovascular diseases is greater in HIV/AIDS patients as compared to the normal
      population. Thus, we aimed to study the predictors of subclinical atherosclerotic
      disease in HIV-infected individuals. Methods: In total, 168 HIV-positive
      individuals below 45 years of age (124 [73.08%] on ART and 44 [26.2%] ART naive)
      along with 150 age- and sex-matched healthy controls were recruited for this
      cross-sectional observational study. Carotid intimal medial thickness (cIMT), a
      surrogate marker of atherosclerosis, was assessed by a carotid colour doppler
      ultrasound and a mean of four measurements (both sides) were taken. cIMT was
      correlated with the age of the individuals, duration and type of ART, duration of
      disease and the level of immunodeficiency (CD4 cell count) along with
      conventional cardiac risk markers. Results: In 168 HIV-positive individuals, the
      mean CD4 cell count was 332.41 +/-17.1 cells/mm3. The mean cIMT of all HIV
      positive individuals was 0.712 +/-0.039 mm (0.596-0.840 mm) as compared to 0.616
      +/-0.023 mm (0.540-0.655 mm) in HIV-negative individuals (P<0.001). cIMT in HIV
      positive individuals on ART (subgroup A) was 0.723 +/-0.034 mm as compared to
      0.682 +/-0.038 mm in HIV-positive individuals not on ART (subgroup B) (P<0.01).
      Low CD4 cell counts, longer duration of HIV infection, exposure to ART and longer
      duration of ART were found to be independent predictors of a higher cIMT in HIV
      positive subjects whereas age, diastolic blood pressure, low HDL, smoking and
      high BMI were predictors of high cIMT in HIV-negative controls. No difference was
      observed in cIMT among patients on different ART regimens but individuals who
      were on nevirapine had higher cIMT as compared to those who were on efavirenz,
      both non-nucleoside reverse transcriptase inhibitors (NNRTIs). Conclusions:
      Individuals with HIV infection (whether on ART or ART naive) have higher cIMT,
      and therefore a higher atherosclerotic burden, as compared to HIV-negative
      individuals. HIV infection itself, along with ART, overshadows conventional
      cardiac risk markers as a predictor of atherosclerotic disease in these
      individuals.

PMID- 29568550
TI  - Dermatological conditions associated with HIV medication in a cohort of Greek
      patients initiating antiretroviral therapy: 1988-2013.
AB  - Objectives: Treatment of HIV infection has evolved from a single antiretroviral
      agent to combination therapy, which has dramatically improved both the quality of
      life and life expectancy of affected patients. The aim of this study was to
      review HIV treatment-associated dermatological conditions observed in adult
      patients receiving antiretroviral therapy (ART) in a single tertiary care
      referral centre over time. Methods: We reviewed the files of HIV-positive
      patients seen at the Dermatology Department, AIDS Clinic of the Andreas Syggros
      Hospital, Athens, Greece who had initiated ART from 1988 to 2013, for evidence of
      dermatological conditions commonly associated with HIV-related medication.
      Results: Among a cohort of 1329 HIV-positive patients (1155 men and 174 women),
      352 (299 men and 53 women) presented with at least one dermatological condition,
      with a total of 423 conditions diagnosed that could be attributed to HIV-related
      medication. Lipodystrophy (47.42%), and maculopapular (MP) rash (40.6%) were most
      commonly diagnosed. There were three incidence peaks for these reactions, which
      reflected the different types of ART and HIV-related drugs commonly used at the
      time. After 2006, the number of these dermatological conditions declined (15.1%
      of cases) with the availability of newer ART regimens. Conclusions: Early ART was
      accompanied with a high incidence of adverse skin reactions, which have decreased
      over time in association with overall better tolerated treatment regimens for HIV
      infection.

PMID- 29568551
TI  - Crowdsourcing and community engagement: a qualitative analysis of the 2BeatHIV
      contest.
AB  - Background: As HIV cure research advances, it is important to engage local
      communities. Crowdsourcing may be an effective, bottom-up approach. Crowdsourcing
      contests elicit public contributions to solve problems and celebrate finalists.
      We examine the development of a crowdsourcing contest to understand public
      perspectives about HIV cure research. Methods: We used flyers, emails, online
      advertisement and phone calls to recruit a convenience sample of community
      members to participate in focus-group discussions. Participants developed a
      contest name, logo and hashtag. Qualitative analysis identified emergent themes
      in the focus group transcripts. Results: Seventy-one people participated in four
      focus groups. Emergent themes for HIV cure engagement included: (1) emphasising
      collective approaches to HIV cure; (2) dispelling myths to spur discussion; (3)
      using HIV cure as motivation for participation; and (4) using creative community
      engagement. Conclusion: Crowdsourcing contests may be useful for engaging local
      communities, developing culturally tailored awareness campaign messaging, and
      encouraging the public to learn more about HIV cure research.

PMID- 29568552
TI  - Prevalence and factors associated with renal dysfunction in patients on tenofovir
      disoproxil fumarate-based antiretroviral regimens for HIV infection in Southern
      India.
AB  - Objectives: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse
      transcriptase inhibitor commonly used in the treatment of HIV infection. This
      retrospective study aims to establish the prevalence of abnormal renal function
      among patients with HIV receiving TDF, and to investigate the risks for TDF
      related renal dysfunction in this population. Methods: Patients at the YRGCARE
      Medical Centre, Voluntary Health Services, receiving TDF-containing
      antiretroviral (ART) regimens between January 2002 and March 2017, were assessed
      for renal dysfunction using creatinine level and eGFR (DAIDS/NIH) during
      continuum of care. Demographic data and comorbidities were analysed for
      association with TDF toxicity. Data were obtained from the Natural History Study
      Database. Other causes of renal dysfunction were excluded. Results: From the
      14,118 patients on ART between 2002 and 2017 seen in the clinic, 7171 (50.8%)
      were initiated on TDF-containing regimens. Among these, 4400 were on a first-line
      NNRTI regimen, and 2771 on a second-line PI/r regimen, initiated after failure of
      first-line therapy. The majority of patients on ART were male, with a median age
      for the whole sample of 36 years (IQR 30-42). At ART initiation, the median CD4
      cell count was 277 cells/mm3 (IQR 165-421) and the viral load (VL) 31,198 HIV-1
      copies/mL (IQR 400-226,690). Median duration of follow-up was 5.1 years (IQR 2.3
      9.5). The prevalence of renal dysfunction in patients taking TDF was 5.6%.
      Increased age, low BMI, low baseline CD4 cell count, hypertension and diabetes
      were associated with tenofovir toxicity (P<0.05). Concomitant PI use was not
      associated with increased risk for renal dysfunction (P>0.05). Conclusions: The
      prevalence of renal dysfunction associated with TDF in our study population was
      higher than in other well-resourced settings, suggesting the need for increased
      renal parameter monitoring in patients in resource-limited settings. Treatment
      with ART should be initiated earlier and BMI should be maintained >=18.5 kg/m2
      through adequate nutrition and prevention of opportunistic infections. For
      patients with multiple comorbidities, tenofovir alafenamide (TAF) should be
      considered, instead of TDF, to avoid renal dysfunction.

PMID- 29568553
TI  - HIV-associated cognitive performance and psychomotor impairment in a Thai cohort
      on long-term cART.
AB  - Objectives: To assess cognitive performance and psychomotor impairment in an HIV
      positive cohort, well-suppressed on combination antiretroviral therapy (cART), in
      an Asian resource-limited setting. Methods: Cross-sectional sociodemographic and
      cognitive data were collected in 329 HIV-positive and 510 HIV-negative
      participants. Cognitive performance was assessed using the International HIV
      Dementia Scale (IHDS), Montreal Cognitive Assessment (MoCA), WAIS-III Digit
      Symbol, Trail Making A, and Grooved Pegboard (both hands). Psychomotor test
      scores in the HIV-positive participants were converted to Z-scores using scores
      of the HIV-negative participants as normative data. Psychomotor impairment was
      defined as performance on two tests more than 1 standard deviation (SD) from
      controls or more than 2 SD on one test. Multivariate linear and logistic
      regression analyses were used to investigate associations between HIV and non-HIV
      related covariates and poorer cognitive performance and psychomotor impairment.
      Results: HIV-positive participants, mean age 45 (SD 7.69) years received cART for
      a median of 12.1 years (interquartile range [IQR] 9.1-14.4). Median CD4 cell
      count was 563 cells/mm3 (IQR 435-725), and 92.77% had plasma HIV RNA <40
      copies/mL. The adjusted mean differences between HIV-positive versus HIV-negative
      cohorts indicated significantly inferior cognitive performance (tests all
      P<0.001) with increasing age and lower income, independently associated.
      Psychomotor impairment was found (P<0.02) in all tests except the Grooved
      Pegboard non-dominant hand (P=0.48). Psychomotor impairment prevalence was 43% in
      the HIV-positive cohort, associated with male gender and lower income.
      Conclusions: In this study, in individuals with viral suppression rates >90% on
      long-term cART, we found that inferior cognitive performance and psychomotor
      impairment were primarily associated with non-HIV-related factors.

PMID- 29568554
TI  - Highlights from the HTLV-1 symposium at the 2017 Australasian HIV and AIDS
      Conference held jointly with the 2017 Australasian Sexual Health Conference,
      November 2017, Canberra, Australia.
AB  - We are pleased to report on the inaugural HTLV-1 symposium at the 2017
      Australasian HIV and AIDS Conference joint with 2017 Australasian Sexual Health
      Conference in Canberra, Australia. Our understanding of HTLV-1 epidemiology,
      pathogenesis, laboratory diagnostics and treatment options for HTLV-1 diseases
      has advanced tremendously over the last 40 years. However, the awareness of
      healthcare providers and the general population about HTLV-1, and the effective
      promotion and implementation of HTLV-1 transmission-prevention strategies, lag
      behind current knowledge. Here we present a summary of the symposium, plenary and
      poster presentations on HTLV-1.

PMID- 29568555
TI  - Report from the First EPIICAL (Early-treated Perinatally HIV-infected
      Individuals: Improving Children's Actual Life with Novel Immunotherapeutic
      Strategies) General Assembly meeting, 9-11 November 2017, Rome, Italy.

PMID- 29568556
TI  - Highlights from the HIV Cure and Reservoir Symposium, 11-12 September 2017,
      Ghent, Belgium.
AB  - For the second time, the HIV Cure Research Center (HCRC) at Ghent University
      organised the HIV Cure and Reservoir Symposium, in Ghent, Belgium, where in this
      two-day conference, virologists, molecular biologists, immunologists and
      clinicians presented the most recent achievements in the field of HIV cure,
      including data on therapeutic vaccines, HIV remission strategies such as 'shock
      and kill' or 'block and lock', benefits of early ART and potential of
      haematopoietic stem cell transplant in achieving cure. Furthermore, methods to
      characterise and quantify the HIV reservoir were discussed along with HIV
      reservoir characterisation in different body parts, including the central nervous
      system. An HIV activist and representative of a patients' agency also presented
      the patients' perspective on HIV cure. This report is a summary of all topics
      discussed during this symposium.

PMID- 29568557
TI  - Art and viral hepatitis elimination programmes.
AB  - The elimination viral hepatitis requires increased awareness of the viruses that
      cause it by the general population. To this end, the Iran Hepatitis Network held
      the First Drawing and Illustration Contest with the theme of eliminating
      hepatitis. We suggest that artwork provided by the general public could have a
      role in campaigns promoting hepatitis elimination.

PMID- 29568559
TI  - Unconscionable: how the U.S. Supreme Court's jurisprudence lags behind the world
      when it comes to contraception and conscience.
AB  - U.S. Supreme Court jurisprudence undermines access to contraception by permitting
      individuals, institutions, and even corporations to claim religious objections to
      ensuring contraceptive insurance coverage, thus imposing those beliefs on non
      adherents and jeopardizing their access to essential reproductive-health
      services. This jurisprudence is not only harmful but also runs contrary to the
      laws and policies of peer nations, as well as international human rights
      principles, which are more protective of the rights of health-care recipients to
      make their own decisions about contraception free from interference. The United
      States should look to the practice and jurisprudence of other nations and ensure
      that religious exemptions are not permitted to deprive a third party of access to
      contraception.

PMID- 29568560
TI  - Life as an early career researcher: interview with Yu Shrike Zhang.
AB  - Yu Shrike Zhang talks to Francesca Lake, Head of Open Access Publishing: Yu
      Shrike Zhang received his BE degree in biomedical engineering in 2008 from
      Southeast University, PR China and PhD degree in biomedical engineering in 2013
      from Georgia Institute of Technology. He is currently an Instructor of Medicine
      and Associate Bioengineer in the Division of Engineering in Medicine at the
      Brigham and Women's Hospital, Harvard Medical School. His research interests
      include organs-on-chips, biomaterials, bioprinting, biomedical devices,
      biomedical imaging and biosensing with a focus on innovating medical engineering
      technologies to recreate functional tissues and biomimetic tissue models. He was
      also a finalist in the inaugural Future Science Early Career Research Award.

PMID- 29568558
TI  - Regulation of lubricin for functional cartilage tissue regeneration: a review.
AB  - Background: Lubricin is chondrocyte-secreted glycoprotein that primarily conducts
      boundary lubrication between joint surfaces. Besides its cytoprotective function
      and extracellular matrix (ECM) attachment, lubricin is recommended as a novel
      biotherapeutic protein that restore functional articular cartilage. Likewise,
      malfunction of lubrication in damaged articular cartilage caused by complex and
      multifaceted matter is a major concern in the field of cartilage tissue
      engineering. Main body: Although a noticeable progress has been made toward
      cartilage tissue regeneration through numerous approaches such as autologous
      chondrocyte implantation, osteochondral grafts, and microfracture technique, the
      functionality of engineered cartilage is a challenge for complete reconstruction
      of cartilage. Thus, delicate modulation of lubricin along with cell/scaffold
      application will expand the research on cartilage tissue engineering. Conclusion:
      In this review, we will discuss the empirical analysis of lubricin from
      fundamental interpretation to the practical design of gene expression regulation.

PMID- 29568561
TI  - Use of patient-derived xenograft mouse models in cancer research and treatment.

PMID- 29568562
TI  - Fascin is secreted in male's serum: results of a pilot study.
AB  - Aim: Fascin is a 55 kDa globular protein with an important role in cell
      migration. Aim of study was to investigate serum fascin in healthy males.
      Materials & methods: From 1 July 2016 to 31 December 2016, we collected serum
      from 46 males. Serum fascin level was performed using ELISA kit from USBiological
      (Salem, MA, USA). Results: Median age was 64 years. Mean fascin serum level was
      9.84 ng/ml, mean prostate-specific antigen (PSA) was 2.74 ng/ml and mean prostate
      volume was 37.64 cc. The 51-60 years group had a mean of 10.53 ng/ml, the 61-70
      group a mean of 9.7 ng/ml and the 71-80 group had a mean of 9.41 ng/ml fascin
      serum level. Conclusion: Fascin serum level did not differ according to age in
      males.

PMID- 29568563
TI  - A future perspective for regenerative medicine: understanding the concept of
      vibrational medicine.

PMID- 29568564
TI  - Antibodies, synthetic peptides and related constructs for planetary health based
      on green chemistry in the Anthropocene.
AB  - The contemporary Anthropocene is characterized by rapidly evolving complex global
      challenges to planetary health vis-a-vis sustainable development, yet innovation
      is constrained under the prevailing precautionary regime that regulates
      technological change. Small-molecule xenobiotic drugs are amenable to efficient
      large-scale industrial synthesis; but their pharmacokinetics, pharmacodynamics,
      interactions and ultimate ecological impact are difficult to predict, raising
      concerns over initial testing and environmental contamination. Antibodies and
      similar agents can serve as antidotes and drug buffers or vehicles to address
      patient safety and decrease dosing requirements. More generally, peptidic agents
      including synthetic peptide-based constructs exemplified by vaccines can be used
      together with or instead of nonpeptidic xenobiotics, thus enabling advances in
      planetary health based on principles of green chemistry from manufacturing
      through final disposition.

PMID- 29568565
TI  - Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin
      dose in Gaza-Palestine.
AB  - Aim: To evaluate applicability of CYP2C9*2, *3 and VKORC1-1639G > A based
      algorithm to predict warfarin stable dose (WSD) in a group of Palestinian
      patients. Patients & methods: Warfarin doses were retrospectively calculated for
      101 Palestinian patients under warfarin therapy using three models. Performance
      of the three models was assessed in 47 patients found to take WSD. Results:
      Frequency of CYP2C9*2, *3 and VKORC1-1639G > A alleles is 13.6, 0.0 and 46.5%
      respectively. The international warfarin pharmacogenetics consortium algorithm
      was more reliable (MAE = 8.9 +/- 1.4; R2 = 0.350) than both the clinical
      algorithm (MAE = 10.4 +/- 1.4; R2 = 0.128;) and the fixed-dose algorithm (MAE =
      11.1 +/- 1.7). Conclusion: The international warfarin pharmacogenetics consortium
      algorithm can be reliably applied for predicting the WSD in Palestinian
      population.

PMID- 29568566
TI  - Could dietary glutamate be contributing to the symptoms of obsessive-compulsive
      disorder?
AB  - A 50-year-old man who had suffered from daily obsessive-compulsive disorder (OCD)
      symptoms for 39 years, in addition to fibromyalgia and irritable bowel syndrome
      symptoms, was enrolled in a randomized double-blind placebo-controlled clinical
      trial to test the effects of a low-glutamate diet on fibromyalgia/irritable bowel
      syndrome symptoms. After 1 month on the low-glutamate diet all of his symptoms
      remitted, including his OCD, which had previously been nonresponsive to
      pharmacological treatment. This case study is limited by self-report of symptoms;
      however, glutamatergic neurotransmission appears to be dysregulated in OCD,
      suggesting biological plausibility for this observation. Future research is
      needed.

PMID- 29568568
TI  - Series of screening compounds with high hit rates for the exploration of multi
      target activities and assay interference.
AB  - Aim: Generation of a database of analog series (ASs) with high assay hit rates
      for the exploration of assay interference and multi-target activities of
      compounds. Methodology: ASs were computationally extracted from extensively
      tested screening compounds with high hit rates. Data: A total of 6941 ASs were
      assembled comprising 14,646 unique compounds that were tested in a total of 1241
      different assays covering 426 specified targets. These ASs were organized and
      prioritized on the basis of different activity and assay frequency criteria. All
      ASs and associated information are made available in an open access deposition.
      Next steps: The large set of ASs will be further analyzed computationally and
      from a chemical perspective to identify assay interference compounds and
      candidates for exploring target promiscuity.

PMID- 29568567
TI  - Key genes and regulatory networks involved in the initiation, progression and
      invasion of colorectal cancer.
AB  - Aim: Until now, identification of drug targets for treatment of patients with
      specific stages of colorectal cancer (CRC) has remained a challenging field of
      research. Herein, we aimed to identify the key genes and regulatory networks
      involved in each stage of CRC. Results: The results of gene expression profiles
      were integrated with protein-protein interaction networks, and topologically
      analyzed. The most important regulatory genes (e.g., CDK1, UBC, ESR1 and ATXN1)
      and signaling pathways (e.g., Wnt, MAPK and JAK-STAT) in CRC initiation,
      progression and metastasis were identified. In vitro analysis confirmed some in
      silico findings. Conclusion: Our study introduces functional hub genes,
      subnetworks, prioritizes signaling pathways and novel biomarkers in CRC that may
      guide further development of targeted therapy programs.

PMID- 29568569
TI  - Polysaccharide-mediated synthesis of melanins from serotonin and other 5-hydroxy
      indoles.
AB  - Aim: As a continuation of our research on the melanin formation from
      catecholamines, we studied the polysaccharide-mediated oxidation of serotonin and
      other 5-hydroxy indoles into melanin-like materials. As for the catecholamines,
      we observed that many polysaccharides promote the oxidation of such compounds,
      particularly in the presence of Cu2+. Methodology: The reactions were monitored
      using reverse phase-HPLC and size-exclusion chromatography techniques. Melanin
      like materials were purified through dialysis and characterized using UV-Vis and
      Fourier transform IR spectroscopic techniques. Results: One such material,
      synthesized from chondroitin sulfate type A and serotonin in the presence of Cu2+
      was found to affect the release of IL-1beta and IL-6 cytokines from immune cells.

PMID- 29568570
TI  - Opportunities and challenges for hybrid immunoaffinity LC-MS approach for
      quantitative analysis of protein biomarkers.

PMID- 29568571
TI  - Analysis of cytomegalovirus-specific T-cell responses in patients with
      hypertension: comparison of assay methods and antigens.
AB  - Background: Recent studies suggest an association between cytomegalovirus (CMV)
      infection and hypertension. In the present study, we used a variety of antigens
      and different assay methods to investigate the relationship between CMV-specific
      T-cell responses and arterial stiffness in patients with hypertension. Methods:
      To evaluate arterial stiffness, pulse wave velocity (PWV) was measured in 207
      hypertensive patients (average age, 63 +/- 8 years). To measure CMV pp65 and IE-1
      specific T-cell responses, we performed intracellular cytokine staining (ICS) and
      enzyme-linked immunospot (ELISPOT) assays. We also analyzed CMV-specific T-cell
      responses against 10 different CMV antigens using ELISPOT assays. Results: In
      patients with hypertension, senescent CD8+ T-cell frequencies were significantly
      correlated with arterial stiffness. Moreover, arterial stiffness was
      independently associated with CMV pp65-specific CD8+ T-cell responses as measured
      by ICS. CMV-specific CD8+ T-cell responses measured by ICS and ELISPOT assays
      showed good agreement and significant correlation with each other. ELISPOT
      analyses against 10 different CMV antigens revealed a consistent response pattern
      irrespective of age, gender, and diabetes. Conclusions: CMV pp65-specific CD8+ T
      cell responses were independently correlated with arterial stiffness in patients
      with hypertension. Additionally, the results of ICS and ELISPOT assays showed a
      significant correlation and good agreement with each other. These findings are
      important for guiding choices regarding the broad clinical application of CMV
      specific T-cell response assays in this patient population.

PMID- 29568572
TI  - Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of
      prematurity: a case series.
AB  - Purpose: Reporting a special clinical finding after intravitreal bevacizumab
      monotherapy for retinopathy of prematurity. Methods: In a retrospective case
      series, the clinical courses of five premature infants with similar vitreous
      changes after a single dose of intravitreal bevacizumab (IVB) injection without
      additional laser therapy were reported. Results: The mean post-conceptional age
      at IVB injection was 39.8 +/- 2.2 (range 37-43) weeks. Localized vitreous
      syneresis and linear fibrotic vitreous condensation occurred 8.2 +/- 2.3 weeks
      after IVB monotherapy in our patients (15.5% of injections). The mean last post
      injection visit was 61.6 +/- 5.3 weeks (post-conceptional age). Further
      regression and complete retinal vascularization occurred in all patients.
      Conclusions: Thread-like vitreous condensation with localized vitreous
      liquefaction may be related to involutional ROP disease itself, combined to anti
      VEGF therapy and may be a predictor factor for further regression and retinal
      vascularization. The case series describes a successful response to anti-VEGF
      monotherapy with no further complications.

PMID- 29568573
TI  - In vitro multichannel single-unit recordings of action potentials from mouse
      sciatic nerve.
AB  - Electrode arrays interfacing with peripheral nerves are essential for
      neuromodulation devices targeting peripheral organs to relieve symptoms. To
      modulate (i.e., single-unit recording and stimulating) individual peripheral
      nerve axons remains a technical challenge. Here, we report an in vitro setup to
      allow simultaneous single-unit recordings from multiple mouse sciatic nerve
      axons. The sciatic nerve (~30 mm) was harvested and transferred to a tissue
      chamber, the ~5mm distal end pulled into an adjacent recording chamber filled
      with paraffin oil. A custom-built multi-wire electrode array was used to
      interface with split fine nerve filaments. Single-unit action potentials were
      evoked by electrical stimulation and recorded from 186 axons, of which 49.5% were
      classed A-type with conduction velocities (CV) greater than 1 m/s and 50.5% were
      C-type (CV < 1 m/s). The single-unit recordings had no apparent bias towards A-
      or C-type axons, were robust and repeatable for over 60 minutes, and thus an
      ideal opportunity to assess different neuromodulation strategies targeting
      peripheral nerves. For instance, ultrasonic modulation of action potential
      transmission was assessed using the setup, indicating increased nerve conduction
      velocity following ultrasound stimulus. This setup can also be used to
      objectively assess the design of next-generation electrode arrays interfacing
      with peripheral nerves.

PMID- 29568574
TI  - Visual loss in HIV-associated cryptococcal meningitis: A case series and review
      of the mechanisms involved.
AB  - Permanent visual loss is a devastating yet preventable complication of
      cryptococcal meningitis. Early and aggressive management of cerebrospinal fluid
      pressure in conjunction with antifungal therapy is required. Historically, the
      mechanisms of visual loss in cryptococcal meningitis have included optic neuritis
      and papilloedema. Hence, the basis of visual loss therapy has been steroid
      therapy and intracranial pressure lowering without clear guidelines. With the use
      of high-resolution magnetic resonance imaging of the optic nerve, an additional
      mechanism has emerged, namely an optic nerve sheath compartment syndrome (ONSCS)
      caused by severely elevated intracranial pressure and fungal loading in the peri
      optic space. An improved understanding of these mechanisms and recognition of the
      important role played by raised intracranial pressure allows for more targeted
      treatment measures and better outcomes. In the present case series of 90 HIV co
      infected patients with cryptococcal meningitis, we present the clinical and
      electrophysiological manifestations of Cryptococcus-induced visual loss and
      review the mechanisms involved.

PMID- 29568575
TI  - Neuroendocrine tumour in a patient with neurofibromatosis type 1 and HIV.
AB  - We report the case of an HIV-positive female patient with neurofibromatosis type
      1 who was treated for recurrent peptic ulcer disease and later developed diabetes
      mellitus and chronic diarrhoea. A metastasising somatostatinoma was
      histologically proven and evidence of a concomitant gastrin-producing
      neuroendocrine tumour was found. Neuroendocrine tumours (NETs) are very rare
      neoplasms originating from a wide variety of endocrine and nervous system tissue
      with the ability to produce different hormones. A somatostatin- and gastrin
      secreting NET in a patient with HIV has not been reported in the literature, to
      the best of our knowledge. We discuss oncogenic pathomechanisms related to the
      underlying conditions and propose stringent monitoring for tumours in HIV
      positive patients with phakomatoses as well as initiation of antiretroviral
      therapy.

PMID- 29568576
TI  - New law on HIV testing in Botswana: The implications for healthcare
      professionals.
AB  - Background: Botswana is one of the countries with the highest HIV prevalence
      rates in the world. Innovative HIV testing strategies are required to ensure that
      those infected or at risk of infection become aware of their HIV status and are
      able to access treatment, care and support. Despite this public health
      imperative, HIV testing strategies in Botswana will in future be based around the
      principles in the new Public Health Act (2013). The present article describes the
      HIV testing norms in the Act, and sets out the strengths and weaknesses of this
      approach and its implications for healthcare professionals in Botswana.
      Objectives: To compare international norms on HIV testing with the provisions
      governing such testing in the new Botswana Public Health Act and to assess the
      extent to which the new Act meets international human rights norms on HIV
      testing. Method: A 'desktop' review of international human rights norms and those
      in the Botswana Public Health Act. Conclusion: HIV testing norms in the new
      Public Health Act in Botswana violate individual rights and will place healthcare
      workers in a position where they will have to elect between acting lawfully or
      ethically. Law reform is required in order to ensure that HIV testing achieves
      the joint goals of public health and human rights.

PMID- 29568577
TI  - Evaluation of selected aspects of the Nutrition Therapeutic Programme offered to
      HIV-positive women of child-bearing age in Western Cape Province, South Africa.
AB  - Background: The Nutrition Therapeutic Programme (NTP) involves the provision of
      food supplements at primary health clinics (PHCs) to correct nutritional
      deficiencies in vulnerable groups. Although previous studies have identified
      problems with implementing the programme at PHCs, assessments of its efficiency
      have been scarce. Objective: To evaluate implementation of the NTP at PHCs that
      provide antiretroviral therapy. Methods: A cross-sectional, descriptive study was
      conducted at 17 PHCs located within 3 districts of Western Cape Province. Two
      target groups were chosen: 32 staff members working at the sites and 21 women of
      child-bearing age enrolled in the NTP. Questionnaires were used to obtain data.
      Results: Only 2 women (10%) lived in food-secure households; the rest were either
      at risk of hunger (29%) or classified as hungry (61%). Most of the women knew
      they had to take the supplements to improve their nutritional status, but the
      majority only recalled receiving basic nutritional advice, and the information
      was mainly given verbally. Ten of the women had shared their supplements with
      others, mostly with their children. The study identified lack of clearly defined
      NTP responsibilities at the PHCs, causing confusion amongst the staff. Although
      many staff members expressed problems with the NTP, only 38% of them reported
      having routine evaluations regarding the programme. Conclusion: Several aspects
      compromised the effectiveness of the NTP, including socio-economic factors
      leading to clients' non-compliance. The strategic organisation and implementation
      of the NTP varied between different PHCs offering antiretroviral therapy, and
      staff experienced difficulties with the logistics of the programme.

PMID- 29568578
TI  - Gestational trophoblastic neoplasm and women living with HIV and/or AIDS.
AB  - The 2011 World Health Organization global report on HIV and/or AIDS estimated
      that sub-Saharan Africa comprised 67% of the global HIV burden, with a current
      estimate of 5.9 million cases in South Africa. Since the introduction of
      antiretroviral therapy, there has been an increase in the incidence of non-AIDS
      defining cancers. Gestational trophoblastic neoplasm (GTN) is a rare pregnancy
      related disorder with an incidence ranging from 0.12-0.7/1000 pregnancies in
      Western nations. The overall cure rate is about 90%. Response to treatment for
      GTN is generally favourable; but the sequelae of HIV and/or AIDS, the resultant
      low CD4 counts, comorbidities, poor performance status and the extent of
      metastatic disease in patients receiving chemotherapy, compromise the prognosis
      and survival.

PMID- 29568579
TI  - Impact of combination antiretroviral therapy initiation on adherence to
      antituberculosis treatment.
AB  - Background: Healthcare workers are often reluctant to start combination
      antiretroviral therapy (ART) in patients receiving tuberculosis (TB) treatment
      because of the fear of high pill burden, immune reconstitution inflammatory
      syndrome, and side-effects. Object: To quantify changes in adherence to
      tuberculosis treatment following ART initiation. Design: A prospective
      observational cohort study of ART-naive individuals with baseline CD4 count
      between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care
      clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by
      pill count, self-report, and electronic Medication Event Monitoring System
      (eMEMS) before and after initiation of ART. Results: ART tended to negatively
      affect adherence to TB treatment, with an 8% - 10% decrease in the proportion of
      patients adherent according to pill count and an 18% - 22% decrease in the
      proportion of patients adherent according to eMEMS in the first month following
      ART initiation, independent of the cut-off used to define adherence (90%, 95% or
      100%). Reasons for non-adherence were multifactorial, and employment was the only
      predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence
      interval 1.06-16.0). Conclusion: Adherence support in the period immediately
      following ART initiation could optimise treatment outcomes for people living with
      TB and HIV.

PMID- 29568580
TI  - Factors associated with retention in HIV care at Sediba Hope Medical Centre.
AB  - Background: Lost to follow-up (LTFU) is a major challenge that hinders the
      success of antiretroviral treatment (ART). Objective: To identify factors
      conducted to a low LTFU rate. Methods: We conducted a two-part descriptive and
      quantitative study. Part 1 comprised interviews with clinic staff to determine
      their perspectives on LTFU and to establish the clinic's follow-up procedures for
      patients on ART. Part 2 of the study was a retrospective review of clinic and
      patient records. LTFU patients were identified and those with contact details
      were contacted for telephonic interview to determine if they were still on ART
      and/or their reasons for becoming LTFU. Results: A low LTFU rate (7.9%; N = 683)
      was identified. Work-related stress, and lack of transport and funds were
      reported reasons for LTFU. Monthly visits, non-adherent defaulters and LTFU
      patients were tracked by an electronic system (SOZO). Factors contributing to
      high rates of retention in care were: location of the clinic in the inner city,
      thus in close proximity to patients' homes or work; clinic operating on
      Saturdays, which was convenient for patients who could not attend during the
      week; an appointment/booking system that was in place and strictly adhered to; a
      reminder SMS being sent out the day before an appointment; individual counselling
      sessions at each visit and referrals where necessary; and a stable staff
      complement and support group at the clinic. Conclusion: Achieving a low LTFU rate
      is possible by having a patient-centred approach and monitoring systems in place.

PMID- 29568581
TI  - A case of emmonsiosis in an HIV-infected child.
AB  - Opportunistic fungal infections can cause significant morbidity and mortality in
      immunocompromised patients. We describe a paediatric case of an unusual
      disseminated fungal infection. A three-year-old HIV-infected child with severe
      immunosuppression (CD4+ T-cell count 12 * 106/L) was admitted to hospital with
      pneumonia, gastroenteritis and herpes gingivostomatitis. Despite antibacterial
      and antiviral therapy, he experienced high fevers and developed an erythematous
      maculopapular rash and abdominal tenderness. The child's condition progressively
      worsened during the admission. A thermally dimorphic fungus was cultured from
      bone marrow and identified as an Emmonsia species on DNA sequencing. The patient
      made a good recovery on amphotericin B deoxycholate and antiretroviral therapy.
      Itraconazole was continued for a minimum of 12 months, allowing for immune
      reconstitution to occur. This case is the first documented description of
      disseminated disease caused by a novel Emmonsia species in an HIV-infected child
      in South Africa.

PMID- 29568582
TI  - Choice or no choice? The need for better branded public sector condoms in South
      Africa.
AB  - Condoms are one of the cornerstones to any response to the HIV epidemic. However,
      targeted marketing strategies that make condoms more attractive to people at high
      risk of infection are often overlooked. The South African National Department of
      Health has recently purchased more attractive condoms to distribute in higher
      education settings free of charge, targeting at-risk youth including young women.
      The authors applaud this move but note the importance of expanding better branded
      condoms to young people elsewhere - for example, via youth clinics and in high
      schools. Exploratory, routine data from Medecins Sans Frontieres in Khayelitsha
      are presented, showing the popularity of alternatives to the government's
      'Choice' brand.

PMID- 29568583
TI  - Routine cranial computed tomography before lumbar puncture in HIV-positive adults
      presenting with seizures at Mitchells Plain Hospital, Cape Town.
AB  - Background: Current international guidelines recommend that a cranial computed
      tomography (CT) be performed on all HIV-positive patients presenting with new
      onset seizures, before a lumbar puncture (LP) is performed. In the South African
      setting, however, this delay could be life threatening. The present study sought
      to measure the number of cranial CTs that contraindicate an LP and to predict
      which clinical signs and symptoms are likely to pose an increased risk from LP.
      Methods: The study was performed at a district level hospital in Western Cape
      Province. Data were collected retrospectively from October 2013 to October 2014.
      Associations between categorical variables were analysed using Pearson's chi
      squared test. Generalised linear regression was used to estimate prevalence
      ratios. Results: One hundred out of 132 patients were studied. Brain shift
      contraindicated an LP in 5% of patients. Patients with brain shift presented with
      decreased level of consciousness, focal signs, headache and neck stiffness.
      Twenty-five per cent of patients had a space-occupying lesion (SOL) (defined as a
      discrete lesion that has a measurable volume) or cerebral oedema. Multivariate
      analysis showed a CD4 count <50 (p = 0.033) to be a statistically significant
      predictor of patients with SOL and cerebral oedema. Univariate analysis showed
      focal signs (p = 0.0001), neck stiffness (p = 0.05), vomiting (p = 0.018) and a
      Glascow Coma Scale (GCS) < 15 (p = 0.002) to be predictors of SOL and cerebral
      oedema. Conclusion: HIV-positive patients with seizures have a high prevalence of
      SOL and cerebral oedema but the majority of them are safe for LP. Doctors can use
      clinical parameters to determine which patients can undergo immediate LP.

PMID- 29568584
TI  - Reconciling the science and policy divide: The reality of scaling up
      antiretroviral therapy in South Africa.
AB  - With the world's largest national treatment programme and over 340 000 incident
      cases annually, the response to HIV in South Africa is hotly contested and there
      is sometimes a dissonance between activism, science and policy. Too often,
      policy, whilst well intentioned, is informed only by epidemiological data. The
      state of the healthcare system and sociocultural factors drive and shape the
      epidemic and its response. By analysis of the financial, infrastructural, human
      resources for health, and governance landscape in South Africa, we assess the
      feasibility and associated costs of implementing a universal test and treat
      programme. We situate a universal test and treat strategy within the governance,
      fiscal, human resources for health, and infrastructural landscape in South
      Africa. We argue that the response to the epidemic must be forward thinking,
      progressive and make the most of the benefits from treatment as prevention.
      However, the logistics of implementing a universal test and treat strategy mean
      that this option is problematic in the short term. We recommend a health systems
      strengthening HIV treatment and prevention approach that includes scaling up
      treatment (for treatment and prevention) along with a range of other prevention
      strategies.

PMID- 29568585
TI  - Care of HIV-exposed and HIV-infected neonates.

PMID- 29568586
TI  - Antiretroviral therapy during the neonatal period.

PMID- 29568587
TI  - HIV testing during the neonatal period.

PMID- 29568588
TI  - Reasons for failure of prevention of mother-to-child HIV transmission in a rural
      South African district hospital.
AB  - Further reduction of mother-to-child transmission (MTCT) of HIV requires improved
      understanding of the reasons for MTCT. We reviewed maternal and infant case notes
      for HIV-positive infants diagnosed by polymerase chain reaction at Bethesda
      Hospital. Nineteen cases were analysed. Median gestation at first antenatal
      consultation (ANC) was 22.5 (interquartile range [IQR] 19.25-24). Eleven (57.9%)
      mothers were HIV positive at first ANC, whilst eight tested negative and later
      positive (2 antepartum, 6 postpartum). Median maternal CD4 was 408 cells/MUL (IQR
      318-531). Six (31.6%) received no antenatal antiretroviral therapy (ART) because
      they were diagnosed as HIV positive postpartum; 9 (47.3%) received antenatal ART
      and 3 (15.8%) were never initiated on ART. At 6 weeks postpartum, 5 infants
      (26.3%) were not on prophylactic nevirapine (NVP) because their mothers had not
      yet been diagnosed. Maternal seroconversion in pregnancy and breastfeeding, and
      possibly false-negative HIV tests, were important reasons for prevention of
      mother-to-child transmission (PMTCT) failure.

PMID- 29568589
TI  - Outcomes from the implementation of a counselling model supporting rapid
      antiretroviral treatment initiation in a primary healthcare clinic in
      Khayelitsha, South Africa.
AB  - Background: Lengthy antiretroviral treatment (ART) preparation contributes to
      high losses to care between communicating ART eligibility and initiating ART. To
      address this shortfall, Medecins Sans Frontieres implemented a revised approach
      to ART initiation counselling preparation (integrated for TB co-infected
      patients), shifting the emphasis from pre-initiation sessions to addressing
      common barriers to adherence and strengthening post-initiation support in a
      primary healthcare facility in Khayelitsha, South Africa. Methods: An
      observational cohort study was conducted using routinely collected data for all
      ART-eligible patients attending their first counselling session between 23 July
      2012 and 30 April 2013 to assess losses to care prior to and post ART initiation.
      Viral load completion and suppression rates of those retained on ART were also
      calculated. Results: Overall, 449 patients enrolled in the study, of whom 3.6%
      did not return to the facility to initiate ART. Of those who were initiated,
      96.7% were retained at their first ART refill visit and 85.9% were retained 6
      months post ART initiation. Of those retained, 80.2% had a viral load taken
      within 6 months of initiating ART, with 95.4% achieving viral load suppression.
      Conclusions: Adapting counselling to enable rapid ART initiation is feasible and
      has the potential to reduce losses to care prior to ART initiation without
      increasing short-term losses thereafter or compromising patient adherence.

PMID- 29568590
TI  - A prospective study of demographic features and quality of life in HIV-positive
      women with cervical cancer treated at Tygerberg Hospital.
AB  - Background: Cervical cancer and human immunodeficiency virus (HIV)
      infection/acquired immune deficiency syndrome (AIDS) both have a high incidence
      in South Africa. Cervical cancer treatment of HIV-positive women poses
      challenges. Treatment-related changes in quality of life (QOL) of such women are
      important to future treatment protocols. Aim: To examine demographic data of HIV
      negative and HIV-positive women at diagnosis of cervical cancer and describe
      their changes in QOL as a result of treatment. Methods and materials: All newly
      diagnosed patients with cervical cancer at Tygerberg Hospital were approached to
      participate in the study. The European Organisation for Research and Treatment of
      Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the Cervix Cancer
      Module (QLQ-CX24) were used. General QOL was measured with the EORTC QLQ-C30 and
      cervical-specific QOL with the QLQ-CX24 questionnaire. The patients completed the
      questionnaire at diagnosis, on completion of treatment and at 3 months' follow
      up. Results: The study included a total of 221 women of whom 22% were HIV
      positive; the latter were younger and of higher educational level than the rest.
      Mean monthly income and stage distribution was similar between the two groups.
      HIV-positive patients underwent radiation therapy more commonly than
      chemoradiation. HIV-positive women showed statistically significantly higher loss
      to follow-up during the study. HIV-positive women experienced no improvement in
      insomnia, appetite loss, nausea, vomiting, diarrhoea, social role or any of the
      sexual domains. In contrast, HIV-negative women experienced statistically
      significant improvement in all sexual domains other than sexual/vaginal
      functioning. The QOL improvement of HIV-negative women was statistically
      significantly greater than their HIV-positive counterparts in the majority of QOL
      domains. Global health improved in both groups, with HIV-negative women
      experiencing greater improvement. HIV-positive women experienced an initial
      decline of peripheral neuropathy (PN) symptoms post treatment with a return to
      pretreatment values at 3 months' follow-up. The change in PN was statistically
      significant between the HIV-negative and HIV-positive women. Conclusion:
      Demographic differences exist between the HIV-negative and HIV-positive groups.
      The differential outcome in the QOL of HIV-positive and HIV-negative women
      treated for cervical cancer might be related to persistence of AIDS-related
      symptoms on completion of cervical cancer treatment.

PMID- 29568591
TI  - Recognising and managing increased HIV transmission risk in newborns.
AB  - Prevention of mother-to-child transmission (PMTCT) programmes have improved
      maternal health outcomes and reduced the incidence of paediatric HIV, resulting
      in improved child health and survival. Nevertheless, high-risk vertical exposures
      remain common and are responsible for a high proportion of transmissions. In the
      absence of antiretrovirals (ARVs), an 8- to 12-hour labour has approximately the
      same 15% risk of transmission as 18 months of mixed feeding. The intensity of
      transmission risk is highest during labour and delivery; however, the brevity of
      this intra-partum period lends itself to post-exposure interventions to reduce
      such risk. There is good evidence that infant post-exposure prophylaxis (PEP)
      reduces intra-partum transmission even in the absence of maternal prophylaxis.
      Recent reports suggest that infant combination ARV prophylaxis (cARP) is more
      efficient at reducing intra-partum transmission than a single agent in situations
      of minimal pre-labour prophylaxis. Guidelines from the developed world have
      incorporated infant cARP for increased-risk scenarios. In contrast, recent
      guidelines for low-resource settings have rightfully focused on reducing
      postnatal transmission to preserve the benefits of breastfeeding, but have
      largely ignored the potential of augmented infant PEP for reducing intra-partum
      transmissions. Minimal pre-labour prophylaxis, poor adherence in the month prior
      to delivery, elevated maternal viral load at delivery, spontaneous preterm labour
      with prolonged rupture of membranes and chorioamnionitis are simple clinical
      criteria that identify increased intra-partum transmission risk. In these
      increased-risk scenarios, transmission frequency may be halved by combining
      nevirapine and zidovudine as a form of boosted infant PEP. This strategy may be
      important to reduce intra-partum transmissions when PMTCT is suboptimal.

PMID- 29568593
TI  - HIV testing and antiretroviral therapy initiation at birth: Views from a primary
      care setting in Khayelitsha.

PMID- 29568592
TI  - Research gaps in neonatal HIV-related care.
AB  - The South African prevention of mother to child transmission programme has made
      excellent progress in reducing vertical HIV transmission, and paediatric
      antiretroviral therapy programmes have demonstrated good outcomes with increasing
      treatment initiation in younger children and infants. However, both in South
      Africa and across sub-Saharan African, lack of boosted peri-partum prophylaxis
      for high-risk vertical transmission, loss to follow-up, and failure to initiate
      HIV-infected infants on antiretroviral therapy (ART) before disease progression
      are key remaining gaps in neonatal HIV-related care. In this issue of the
      Southern African Journal of HIV Medicine, experts provide valuable
      recommendations for addressing these gaps. The present article highlights a
      number of areas where evidence is lacking to inform guidelines and programme
      development for optimal neonatal HIV-related care.

PMID- 29568594
TI  - Breastfeeding and the 2015 South African guidelines for prevention of mother-to
      child transmission of HIV.

PMID- 29568595
TI  - How ready are our health systems to implement prevention of mother to child
      transmission Option B+?
AB  - In January 2015, the South African National Department of Health released new
      consolidated guidelines for the prevention of mother to child transmission
      (PMTCT) of HIV, in line with the World Health Organization's (WHO) PMTCT Option
      B+. Implementing these guidelines should make it possible to eliminate mother to
      child transmission (MTCT) of HIV and improve long-term maternal and infant
      outcomes. The present article summarises the key recommendations of the 2015
      guidelines and highlights current gaps that hinder optimal implementation; these
      include late antenatal booking (as a result of poor staff attitudes towards
      'early bookers' and foreigners, unsuitable clinic hours, lack of transport to
      facilities, quota systems being applied to antenatal clients and clinic staff
      shortages); poor compliance with rapid HIV testing protocols; weak referral
      systems with inadequate follow-up; inadequate numbers of laboratory staff to
      handle HIV-related monitoring procedures and return of results to the correct
      facility; and inadequate supply chain management, leading to interrupted supplies
      of antiretroviral drugs. Additionally, recommendations are proposed on how to
      address these gaps. There is a need to evaluate the implementation of the 2015
      guidelines and proactively communicate with ground-level implementers to identify
      operational bottlenecks, test solutions to these bottlenecks, and develop
      realistic implementation plans.

PMID- 29568596
TI  - HIV counselling and testing in secondary schools: What students want.
AB  - Background: HIV counselling and testing (HCT) is an essential element in the
      response to the HIV epidemic. There are still major research gaps about the best
      ways to provide HCT, especially to the youth, and school-based HCT is a model
      that has been suggested. To make HCT youth friendly and to enhance access to the
      service, the particular needs of the youth need to be addressed. Aim: To explore
      the expressed needs of students about school-based HCT service provision. Method:
      The study was conducted in 6 secondary schools in Cape Town where a mobile HCT
      service is provided by a non-governmental organisation. In each school, two mixed
      gender focus groups were held, one with grades 8 and 9 students and one with
      grades 10 and 11. A total of 91 students aged 13-21 were involved. The focus
      groups were conducted in the students' home language. All groups were audio
      recorded, transcribed verbatim and translated into English. Results: Content data
      analysis was done and the following themes emerged: (1) Where the students want
      HCT to be done, (2) How they want HCT to be done and (3) Who should do the
      counselling. Most students want HCT to be provided in schools on condition that
      their fears and expressed needs are taken into account. They raised concerns
      regarding privacy and confidentiality, and expressed the need to be given
      information regarding HCT before testing is done. They wanted staff providing the
      service to be experienced and trained to work with youth, and they wanted
      students who tested positive to be followed up and supported. Conclusion: To
      increase youth utilisation of the HCT service, their expressed needs should be
      taken into account when developing a model for school-based HCT.

PMID- 29568597
TI  - Guideline on the management of occupational and non-occupational exposure to the
      human immunodeficiency virus and recommendations for post-exposure prophylaxis:
      2015 Update.
AB  - This guideline is an update of the post-exposure prophylaxis (PEP) guideline
      published by the Southern African HIV Clinicians Society in 2008. It updates the
      recommendations on the use of antiretroviral medications to prevent individuals
      who have been exposed to a potential HIV source, via either occupational or non
      occupational exposure, from becoming infected with HIV. No distinction is made
      between occupational or non-occupational exposure, and the guideline promotes the
      provision of PEP with three antiretroviral drugs if the exposure confers a
      significant transmission risk. The present guideline aligns with the principles
      of the World Health Organization PEP guidelines (2014), promoting simplification
      and adherence support to individuals receiving PEP.

PMID- 29568598
TI  - Southern African HIV Clinicians Society adult antiretroviral therapy guidelines:
      Update on when to initiate antiretroviral therapy.
AB  - The most recent version of the Southern African HIV Clinicians Society's adult
      antiretroviral therapy (ART) guidelines was published in December 2014. In the 27
      August 2015 edition of the New England Journal of Medicine, two seminal
      randomised controlled trials that addressed the optimal timing of ART in HIV
      infected patients with high CD4 counts were published: Strategic timing of
      antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral
      treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected
      adults). The findings of these two trials were consistent: there was significant
      individual clinical benefit from starting ART immediately in patients with CD4
      counts higher than 500 cells/MUL rather than deferring until a certain lower CD4
      threshold or clinical indication was met. The findings add to prior evidence
      showing that ART reduces the risk of onward HIV transmission. Therefore, early
      ART initiation has the public health benefits of potentially reducing both HIV
      incidence and morbidity. Given this new and important evidence, the Society took
      the decision to provide a specific update on the section of the adult ART
      guidelines relating to when ART should be initiated.

PMID- 29568599
TI  - Hepatitis B co-infection in HIV-infected patients receiving antiretroviral
      therapy at the TC Newman Anti Retroviral Treatment Clinic in Paarl, Western Cape.
AB  - Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co
      infection in South Africa is estimated to be between 5% and 23%; however, only
      limited evidence is available. Co-infection increases the risk of chronification
      of HBV, liver cirrhosis and death. Objective: To assess the HBV and/or HIV co
      infection rate amongst the adult antiretroviral treatment cohort at the TC Newman
      ART Clinic in Paarl, Western Cape. Methods: In a retrospective, cross-sectional
      study, the routine hepatitis B surface antigen screening results for all adult
      HIV patients who were started on antiretroviral treatment over a period of 19
      months were collected and analysed for gender, CD4 count and age. Results:
      Amongst the 498 participants (60% female participants), the Hepatitis B surface
      Antigen positivity rate was 7.6%. Male gender, age between 50 and 59 years and a
      low CD4 count were correlated with higher rates. Conclusion: Useful insight could
      be obtained by analysing routine data. The prevalence of almost 8% confirms the
      need for testing of HIV-positive patients for hepatitis B.

PMID- 29568600
TI  - Feeding practices and nutritional status of HIV-exposed and HIV-unexposed infants
      in the Western Cape.
AB  - Background: Optimal infant- and young child-feeding practices are crucial for
      nutritional status, growth, development, health and, ultimately, survival. Human
      breast milk is optimal nutrition for all infants. Complementary food introduced
      at the correct age is part of optimal feeding practices. In South Africa,
      widespread access to antiretrovirals and a programme to prevent mother-to-child
      transmission of HIV have reduced HIV infection in infants and increased the
      number of HIV-exposed uninfected (HEU) infants. However, little is known about
      the feeding practices and nutritional status of HEU and HIV-unexposed (HU)
      infants. Objective: To assess the feeding practices and nutritional status of HIV
      exposed and HIV-unexposed (HU) infants in the Western Cape. Design: Prospective
      substudy on feeding practices nested in a pilot study investigating the innate
      immune abnormalities in HEU infants compared to HU infants. The main study
      commenced at week 2 of life with the nutrition component added from 6 months.
      Information on children's dietary intake was obtained at each visit from the
      caregiver, mainly the mother. Head circumference, weight and length were recorded
      at each visit. Data were obtained from 6-, 12- and 18-month visits. World Health
      Organization feeding practice indicators and nutrition indicators were utilised.
      Setting: Tygerberg Academic Hospital, Western Cape. Mothers were recruited from
      the postnatal wards. Subjects: Forty-seven mother-infant pairs, 25 HEU and 22 HU
      infants, participated in this nutritional substudy. Eight (17%) infants, one HU
      and seven HEU, were lost to follow-up over the next 12 months. The HEU children
      were mainly Xhosa (76%) and HU were mainly mixed race (77%). Results: The
      participants were from poor socio-economic backgrounds. In both groups, adherence
      to breastfeeding recommendations was low with suboptimal dietary diversity. We
      noted a high rate of sugar- and salt-containing snacks given from a young age.
      The HU group had poorer anthropometric and nutritional indicators not explained
      by nutritional factors alone. However, alcohol and tobacco use was much higher
      amongst the HU mothers. Conclusion: Adherence to breastfeeding recommendations
      was low. Ethnicity and cultural milieu may have influenced feeding choices and
      growth. Further research is needed to understand possible reasons for the poorer
      nutritional and anthropometric indicators in the HU group.

PMID- 29568601
TI  - Treatment outcomes in a rural HIV clinic in South Africa: Implications for health
      care.
AB  - Objective: To assess the treatment outcomes of an HIV clinic in rural Limpopo
      province, South Africa. Methods: A retrospective cohort study involving medical
      records review of HIV-positive patients initiated on antiretroviral treatment
      (ART) was conducted from December 2007 to November 2008 at Letaba Hospital. Data
      on socio-demographic characteristics, CD4 counts, viral loads (VLs),
      opportunistic infections, adverse effects of treatment, hospital admissions, and
      patient retention at 6, 12, 24, and 36 months on ART were collected. Analysis
      included descriptive statistics, chi-square and t-tests. Results: Of 124 patient
      records sampled, the majority of patients were female (69%), single (49%),
      unemployed (56%), living at least 10 km from the hospital (52.4%), and were on
      treatment at 36 months (69%). Approximately 84% of patients achieved viral
      suppression (VLs < 400 copies/mL) by 6 months of ART and the mean CD4 count
      increased from 128 at baseline to 470 cells/mm3 at 24 months. There was a mean
      weight gain of 5.9 kg over the 36 months and the proportion of patients with
      opportunistic infections decreased from 54.8% (n = 68) at baseline to 15.3% (n =
      19) at 36 months. Although the largest improvements in CD4, VLs, and weights were
      recorded in the first 6 months of ART, viral rebound became evident thereafter.
      Of all variables, only age < 50 years and being pregnant were significantly
      associated with higher VLs (p = 0.03). Conclusion: Good treatment outcomes are
      achievable in a rural South African ART clinic. However, early viral rebound and
      higher VLs in pregnancy highlight the need for enhanced treatment adherence
      support, especially for pregnant women to reduce the risk of mother to child
      transmission.

PMID- 29568602
TI  - HIV and/or AIDS awareness among adolescents in a South African at-risk rural
      community.
AB  - Background: The devastating effects of HIV and/or AIDS are widely documented.
      Despite ongoing efforts to address the challenges associated with the pandemic,
      the impact on children orphaned because of the disease, as well as on
      adolescents, remains problematic. More specifically, orphaned adolescents living
      in poverty are particularly vulnerable and are often exposed to, for example,
      emotional and physical abuse and transactional sexual exploitation. Against this
      background, the importance of informed awareness among adolescents is continually
      emphasised, yet the outcomes of awareness campaigns require ongoing research.
      Objectives: The main objective of this study was to explore HIV and/or AIDS
      awareness among adolescents living in a rural community in South Africa, in the
      Chris Hani District of the Eastern Cape Province. Sixteen adolescents (aged 12
      24) who had lost one or both of their parents because of HIV and/or AIDS-related
      reasons were purposefully selected to participate in the study. Method: For this
      qualitative investigation, we implemented a descriptive case study design. Semi
      structured individual interviews, observation and field notes were used to
      collect and document data, and inductive thematic analysis was completed using
      the software programme Atlas.ti 7. Results: The three themes that were identified
      relate to HIV and/or AIDS awareness, disclosure of parents' HIV and/or AIDS
      status and experiences of adolescents surrounding the death of their parents.
      Adolescents of the community viewed HIV and/or AIDS as an infectious disease that
      can lead to death; however, this can be prevented by avoiding at-risk sexual
      behaviour. Schools and family members were the main sources of information
      regarding HIV and/or AIDS to the participants. Even though parents tended not to
      disclose their HIV and/or AIDS status, adolescents became aware of their parents'
      status when reading about this on their parents' medical report cards or when
      being told about the status by others following the death of their parents. For
      adolescents, their parents' deaths were associated with the parents being
      chronically ill or showing visible signs of deterioration such as weight loss.
      Conclusion: The study concludes that even though current campaigns and
      informative interventions have seemingly succeeded in ensuring HIV and/or AIDS
      awareness among adolescents - also those in remote areas - continued educational
      campaigns are important. Such initiatives may prove to be beneficial by focusing
      on ways that parents can discuss HIV and/or AIDS-related issues with their
      children and disclose an HIV-positive status.

PMID- 29568603
TI  - The prevalence of HIV in the sudden, unexplained and unexpected death population
      at the Pretoria Medico-Legal Laboratory.
AB  - Purpose: To determine the prevalence of HIV in the sudden, unexplained and
      unexpected (SUU) death population admitted to the Pretoria Medico-Legal
      Laboratory. Methods: This study was conducted at the Pretoria Medico-Legal
      Laboratory. Blood samples were obtained from decedents who died suddenly and/or
      unexpectedly, during autopsy, by a forensic pathologist. Sample collection
      continued until 100 valid samples were analysed for HIV antibodies. The data
      collected included demographic details and case-related information. Results and
      Conclusion: SUU deaths accounted for 14% of all cases admitted to the Pretoria
      Medico-Legal Laboratory. The HIV prevalence in the SUU deaths was 43%, which is
      17% higher than the general mortuary population in Pretoria (p = 0.0045). The
      majority of these deaths were due to respiratory disease processes, with 12 cases
      having HIV/TB co-infection.

PMID- 29568604
TI  - The profile and frequency of known risk factors or comorbidities for deep vein
      thrombosis in an urban district hospital in KwaZulu-Natal.
AB  - Background: Although deep vein thrombosis (DVT) is a preventable disease, it
      increases the morbidity and mortality in hospitalised, patients, resulting in
      considerable economic health impact. The identification and primary prevention of
      risk factors using risk assessment and stratification with subsequent anti
      thrombotic prophylaxis in moderate- to severe-risk categories is the most
      rational means of reducing morbidity and mortality. Aim and setting: The aim of
      the study was to describe the profile and frequency of known risk factors or
      comorbidities of hospitalised medical patients with ultrasound-diagnosed DVT in
      an urban district hospital in KwaZulu-Natal. Methods: A retrospective review of
      clinical notes of all medical patients (age >= 13 years) admitted to the hospital
      with ultrasound-diagnosed DVT between July and December 2013. Results: The median
      age was 40 years (interquartile range 32-60 years) and female preponderance was
      72.84%. HIV and tuberculosis emerged as the prevalent risk factors, accounting
      for 51.85% and 35.80%, respectively. Other risk factors observed were recent
      hospitalisation (34.57%), smoking (25.93%), previous DVT (19.75%) and congestive
      cardiac failure (18.52%). Conclusion: DVT in our study occurred predominantly in
      young female patients unlike previous studies where patients were generally
      older. Furthermore, HIV and tuberculosis were the two most common known risk
      factors or comorbidities observed. Clinicians should have a heightened awareness
      of venous thromboembolism in patients with either condition or where both
      conditions occur together and appropriate thromboprophylaxis should be
      administered.

PMID- 29568605
TI  - PIMATM point-of-care testing for CD4 counts in predicting antiretroviral
      initiation in HIV-infected individuals in KwaZulu-Natal, Durban, South Africa.
AB  - Introduction: Limited information is available on the usefulness of the PIMATM
      analyser in predicting antiretroviral treatment eligibility and outcome in a
      primary healthcare clinic setting in disadvantaged communities in KwaZulu-Natal,
      South Africa. Materials and methods: The study was conducted under the eThekwini
      Health Unit, Durban, KwaZulu-Natal. Comparison of the enumeration of CD4+ T-cells
      in 268 patients using the PIMATM analyser and the predicate National Health
      Laboratory Services (NHLS) was undertaken during January to July 2013. Bland
      Altman analysis to calculate bias and limits of agreement, precision and levels
      of clinical misclassification at various CD4+ T-cell count thresholds was
      performed. Results: There was high precision of the PIMATM control bead
      cartridges with low and normal CD4+ T-cell counts using three different PIMATM
      analysers (%CV < 5). Under World Health Organization (WHO) guidelines (<= 500
      cells/mm3), the sensitivity of the PIMATM analyser was 94%, specificity 78% and
      positive predictive value (PPV) 95%. There were 24 (9%) misclassifications, of
      which 13 were false-negative in whom the mean bias was 149 CD4+ T-cells/mm3. Most
      (87%) patients returned for their CD4 test result but only 67% (110/164) of those
      eligible (<= 350 cells/mm3) were initiated on antiretroviral therapy (ART) with a
      time to treatment of 49 days (interquartile range [IQR], 42-64 days). Conclusion:
      There was adequate agreement between PIMATM analyser and predicate NHLS CD4+ T
      cell count enumeration (<= 500 cells/mm3) in adult HIV-positive individuals. The
      high PPV, sensitivity and acceptable specificity of the PIMATM analyser
      technology lend it as a reliable tool in predicting eligibility and rapid linkage
      to care in ART programmes.

PMID- 29568607
TI  - What is the role of CD4 count in a large public health antiretroviral programme?

PMID- 29568606
TI  - Immune activation is associated with decreased thymic function in asymptomatic,
      untreated HIV-infected individuals.
AB  - Background: Reduced thymic function causes poor immunological reconstitution in
      human immunodeficiency virus (HIV)-positive patients on combined antiretroviral
      therapy (cART). The association between immune activation and thymic function in
      asymptomatic HIV-positive treatment-naive individuals has thus far not been
      investigated. Aims and objectives: To optimise a five-colour flow cytometric
      assay for measurement of thymic function by measuring recent thymic emigrants
      (RTEs) in treatment-naive HIV-infected patients and healthy controls and
      correlate results with levels of immune activation, CD4 counts and viral load.
      Methods: Blood obtained from 53 consenting HIV-positive individuals and 32
      controls recruited from HIV prevention and testing clinic in Cape Town, South
      Africa. RTEs were measured (CD3+/CD4+/CD45RA+/CD31+/CD62L+) and levels were
      correlated with CD4 counts of HIV-infected individuals, log viral load and levels
      of immune activation (CD8+/CD38+ T-cells). Results: HIV-infected individuals had
      reduced frequencies of RTEs when compared to controls (p = 0.0035). Levels of
      immune activation were inversely correlated with thymic function (p = 0.0403),
      and the thymic function in HIV-infected individuals showed no significant
      correlation with CD4 counts (p = 0.31559) and viral load (p = 0.20628).
      Conclusions: There was impaired thymic function in HIV-infected individuals,
      which was associated with increased levels of immune activation. The thymic
      dysfunction was not associated with CD4 counts and viral load. Immune activation
      may result in inflammatory damage to the thymus and subsequent thymic
      dysfunction, and CD4 counts and viral load may not necessarily reflect thymic
      dysfunction in HIV.

PMID- 29568608
TI  - Compliance to HIV treatment monitoring guidelines can reduce laboratory costs.
AB  - Background: Panel tests are a predetermined group of tests commonly requested
      together to provide a comprehensive and conclusive diagnosis, for example, liver
      function test (LFT). South African HIV antiretroviral treatment (ART) guidelines
      recommend individual tests for toxicity monitoring over panel tests. In 2008, the
      National Health Laboratory Services (NHLS) request form was redesigned to list
      individual tests instead of panel tests and removed the 'other tests' box option
      to facilitate efficient ART laboratory monitoring. Objectives: This study aimed
      to demonstrate changes in laboratory expenditure, for individual and panel tests,
      for ART toxicity monitoring. Method: NHLS Corporate Data Warehouse (CDW) data
      were extracted for HIV conditional grant accounts to assess ART toxicity
      monitoring laboratory expenditure between 2010/2011 and 2014/2015. Data were
      classified based on the tests requested, as either panel (LFT or urea and
      electrolytes) or individual (alanine transaminase or creatinine) tests. Results:
      Expenditure on panel tests reduced from R340 million in 2010/2011 to R140m by
      2014/2015 (reduction of R204m) and individual test expenditure increased from
      R34m to R76m (twofold increase). A significant reduction in LFT panel expenditure
      was noted, reducing from R322m in 2010/2011 to R130m in 2014/2015 (60%
      reduction). Conclusion: Changes in toxicity monitoring guidelines and the re
      engineering of the NHLS request form successfully reduced expenditure on panel
      tests relative to individual tests. The introduction of order entry systems could
      further reduce unnecessary laboratory expenditure.

PMID- 29568609
TI  - Computational models as predictors of HIV treatment outcomes for the Phidisa
      cohort in South Africa.
AB  - Background: Selecting the optimal combination of HIV drugs for an individual in
      resource-limited settings is challenging because of the limited availability of
      drugs and genotyping. Objective: The evaluation as a potential treatment support
      tool of computational models that predict response to therapy without a genotype,
      using cases from the Phidisa cohort in South Africa. Methods: Cases from Phidisa
      of treatment change following failure were identified that had the following data
      available: baseline CD4 count and viral load, details of failing and previous
      antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV
      Resistance Response Database Initiative's (RDI's) models used these data to
      predict the probability of a viral load < 50 copies/mL at follow-up. The models
      were also used to identify effective alternative combinations of three locally
      available drugs. Results: The models achieved accuracy (area under the receiver
      operator characteristic curve) of 0.72 when predicting response to therapy, which
      is less accurate than for an independent global test set (0.80) but at least
      comparable to that of genotyping with rules-based interpretation. The models were
      able to identify alternative locally available three-drug regimens that were
      predicted to be effective in 69% of all cases and 62% of those whose new
      treatment failed in the clinic. Conclusion: The predictive accuracy of the models
      for these South African patients together with the results of previous studies
      suggest that the RDI's models have the potential to optimise treatment selection
      and reduce virological failure in different patient populations, without the use
      of a genotype.

PMID- 29568610
TI  - Recommendations for the management of indeterminate HIV PCR results within South
      Africa's early infant diagnosis programme.
AB  - Indeterminate HIV PCR results represent missed diagnostic opportunities within
      South Africa's early infant diagnosis programme. These results not only delay
      diagnosis and appropriate management but are also a source of confusion and
      apprehension amongst clinicians and caregivers. We describe the extent of
      indeterminate HIV PCR results within South Africa's early infant diagnosis
      programme and provide recommendations for the management of these cases, both in
      terms of laboratory practice and the clinical care of the infants.

PMID- 29568611
TI  - Incidence of neuropsychiatric side effects of efavirenz in HIV-positive treatment
      naive patients in public-sector clinics in the Eastern Cape.
AB  - Background: It is acknowledged that almost half of patients initiated on
      efavirenz will experience at least one neuropsychiatric side effect. Objectives:
      The aim was to determine the incidence and severity of neuropsychiatric side
      effects associated with efavirenz use in five public-sector primary healthcare
      clinics in the Eastern Cape. Method: The study was a prospective drug utilisation
      study. A total of 126 medical records were reviewed to obtain the required
      information. After baseline assessment, follow-up reviews were conducted at 4
      weeks, 12 weeks and 24 weeks from 2014 to 2015. Results: The participant group
      was 74.60% female (n = 94), and the average age was 37.57+/-10.60 years. There
      were no neuropsychiatric side effects recorded for any patient. After the full
      follow-up period, there were a total of 49 non-adherent patients and one patient
      had demised. A non-adherent patient was defined as a patient who did not return
      to the clinic for follow-up assessment and medication refills 30 days or more
      after the appointed date. Some patients (n = 11) had sent a third party to the
      clinic to collect their antiretroviral therapy (ART). The clinic pharmacy would
      at times dispense a two-month supply of medication resulting in the patient
      presenting only every two months. Conclusion: Further pharmacovigilance studies
      need to be conducted to determine the true incidence of these side effects.
      Healthcare staff must be encouraged to keep complete records to ensure meaningful
      patient assessments. Patients being initiated on ART need to personally attend
      the clinic monthly for at least the first 6 months of treatment. Clinic staff
      should receive regular training concerning ART, including changes made to
      guidelines as well as reminders of side effects experienced.

PMID- 29568612
TI  - The end of the line? A case of drug resistance to third-line antiretroviral
      therapy.
AB  - HIV drug resistance has been described in all antiretroviral drug classes and
      threatens the long-term success of HIV treatment. Here, we describe the first
      reported case of acquired resistance to the integrase strand transfer inhibitors
      in South Africa. This case illustrates the dilemma of treatment in the context of
      inadequate adherence and poor psychosocial support and highlights the potential
      risk of transmission of multidrug-resistant virus.

PMID- 29568613
TI  - Southern African guidelines on the safe use of pre-exposure prophylaxis in
      persons at risk of acquiring HIV-1 infection.
AB  - The Southern African HIV Clinicians Society published its first set of oral pre
      exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men
      (MSM) who are at risk of HIV infection. With the flurry of data that has been
      generated in PrEP clinical research since the first guideline, it became evident
      that there was a need to revise and expand the PrEP guidelines with new evidence
      of safety and efficacy of PrEP in several populations, including MSM, transgender
      persons, heterosexual men and women, HIV-serodiscordant couples and people who
      inject drugs. This need is particularly relevant following the World Health
      Organization (WHO) Consolidated Treatment Guidelines released in September 2015.
      These guidelines advise that PrEP is a highly effective, safe, biomedical option
      for HIV prevention that can be incorporated with other combination prevention
      strategies in Southern Africa, given the high prevalence of HIV in the region.
      PrEP should be tailored to populations at highest risk of HIV acquisition, whilst
      further data from studies in the region accrue to guide optimal deployment to
      realise the greatest impact regionally. PrEP may be used intermittently during
      periods of perceived HIV acquisition risk, rather than continually and lifelong,
      as is the case with antiretroviral treatment. Recognition and accurate
      measurement of potential risk in individuals and populations also warrants
      discussion, but are not extensively covered in these guidelines.

PMID- 29568614
TI  - Associations between plasma tenofovir concentration and renal function markers in
      HIV-infected women.
AB  - Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney
      tubular dysfunction and reduced renal function. Limited studies were performed in
      Europe and Asia that related plasma tenofovir (TFV) concentration with renal
      function; no such studies to date have been performed on Africans. Objective: To
      investigate the correlation between plasma tenofovir (TFV) concentration and
      certain renal function markers in HIV-infected women on TDF antiretroviral
      therapy (ART). These markers were also compared to a HIV-uninfected control
      group. Methods: HIV-infected women (n = 30) on TDF-based ART were matched with 30
      controls for age and body mass index. Renal markers analysed were estimated
      glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine,
      albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum
      tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained
      retrospectively for the HIV-infected women. Plasma TFV was assayed using a
      validated HPLC-MS/MS method. Stepwise regression, Mann-Whitney test, unpaired and
      paired t-tests were applied in the statistical analyses. Results: TFV
      concentration was independently associated with albuminuria (adjusted r2 = 0.339;
      p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR (p =
      0.038), CrCl (p = 0.032) and albuminuria (p = 0.048) were significantly higher in
      HIV-infected compared to the uninfected women, but eGFR was abnormally high in
      HIV-infected women. Both eGFR (p < 0.001) and CrCl (p = 0.008) increased from
      baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration
      was associated with increased albuminuria in HIV-infected women in this sub
      study. Both eGFR and CrCl were increased in HIV-infected women from baseline.
      These findings should be confirmed in larger studies, and hyperfiltration in HIV
      infected women warrants further investigation.

PMID- 29568615
TI  - When will sub-Saharan Africa adopt HIV treatment for all?
AB  - Background: The World Health Organization (WHO) HIV treatment guidelines have
      been used by various countries to revise their national guidelines. Our study
      discusses the national policy response to the HIV epidemic in sub-Saharan Africa
      and quantifies delays in adopting the WHO guidelines published in 2009, 2013 and
      2015. Methods: From the Internet, health authorities and experts, and community
      members, we collected 59 published HIV guidelines from 33 countries in the sub
      Saharan African region, and abstracted dates of publication and antiretroviral
      therapy (ART) eligibility criteria. For these 33 countries, representing 97%
      regional HIV burden in 2015, the number of months taken to adopt the WHO 2009,
      2013 and/or 2015 guidelines were calculated to determine the average delay in
      months needed to publish revised national guidelines. Findings: Of the 33
      countries, 3 (6% regional burden) are recommending ART according to the WHO 2015
      guidelines (irrespective of CD4 count); 19 (65% regional burden) are recommending
      ART according to the WHO 2013 guidelines (CD4 count <= 500 cells/mm3); and 11
      (26% regional burden) according to the WHO 2009 guidelines (CD4 count <= 350
      cells/mm3). The average time lag to WHO 2009 guidelines adoption in 33 countries
      was 24 (range 3-56) months. The 22 that have adopted the WHO 2013 guidelines took
      an average of 10 (range 0-36) months, whilst the three countries that adopted the
      WHO 2015 guidelines took an average of 8 (range 7-9) months. Conclusion: There is
      an urgent need to shorten the time lag in adopting and implementing the new WHO
      guidelines recommending 'treatment for all' to achieve the 90-90-90 targets.

PMID- 29568616
TI  - Survival after Pneumocystis jirovecii pneumonia requiring ventilation: A case
      report.
AB  - Pneumocystis pneumonia (PCP) in patients with the human immunodeficiency virus
      (HIV) is associated with a high mortality rate, which increases substantially
      with the need for mechanical ventilation. Local experience of patients with PCP
      admitted to the intensive care unit has revealed mortality rates close to 100%.
      We present a case of a 39-year-old HIV-infected man diagnosed with PCP who was
      successfully weaned from mechanical ventilation after presenting with respiratory
      distress and severe hypoxaemia. A short review of the literature will also be
      presented.

PMID- 29568617
TI  - Health-related quality of life of antiretroviral treatment defaulters in
      Botswana.
AB  - Background: Antiretroviral therapy (ART) improves patients' health-related
      quality of life (HRQoL). Defaulting from ART has detrimental consequences,
      including the development of viral resistance, treatment failure and increased
      risks of disease progression. Little is known about the quality of life of ART
      defaulters and reasons for discontinuing their ART. Objectives: This study sought
      to measure the HRQoL of ART patients in Botswana who were on ART for up to 5
      years but had discontinued treatment for at least 3 months, and to identify
      factors associated with ART defaulting. Method: We conducted a cross-sectional
      study with 104 eligible respondents in four ART clinics in south eastern
      Botswana. We assessed respondents' HRQoL using the World Health Organization
      Quality of Life Questionnaire for HIV short form. Clinical information was
      obtained from respondents' medical records. Data were analysed using SAS version
      9.2. Results: Reasons for discontinuing ART were inaccessible clinics (22.4%),
      feeling better (21.4%), running out of pills (11.2%), depression (8.2%), lack of
      care and/or support (8.2%), failure to understand instructions (7.7%),
      medications' side effects (6.1%) and alcohol abuse (3.1%). In multivariate
      analyses, respondents aged 36-45 years had a 0.03 lower independence HRQoL score
      compared to those aged 35 and younger (beta = -0.03; 95% confidence interval: 
      1.72, -1.66). Despite defaulting from their ART, respondents' calculated HRQoL
      scores were moderate. Conclusion: This study highlights the need to enhance ART
      adherence in order to improve the HRQoL of people living with HIV and/or AIDS.

PMID- 29568618
TI  - Barriers to adherence to antiretroviral treatment in a regional hospital in
      Vredenburg, Western Cape, South Africa.
AB  - Background: South Africa currently runs the largest public antiretroviral
      treatment (ART) programme in the world, with over 80% of people living with HIV
      and/or AIDS on ART. However, in order to appreciate the benefits of using ART,
      patients are subject to uncompromising and long-term commitments of taking at
      least 95% of their treatment as prescribed. Evidence shows that this level of
      adherence is seldom achieved because of a multilevel and sometimes interwoven
      myriad of factors. Objective: We described the challenges faced by patients on
      ART in Vredenburg with regard to ART adherence. Methods: A descriptive
      qualitative research design was used. Eighteen non-adhering patients on ART in
      the Vredenburg regional hospital were purposefully selected. Using a semi
      structured interview guide, we conducted in-depth interviews with the study
      participants in their mother tongue (Afrikaans). The interviews were audio-taped,
      transcribed verbatim and translated into English. The data were analysed manually
      using the thematic content analysis method. Results: Stigma, disclosure,
      unemployment, lack of transport, insufficient feeding, disability grants and
      alternative forms of therapy were identified as major barriers to adherence,
      whereas inadequate follow-ups and lack of patient confidentiality came under
      major criticisms from the patients. Conclusion: Interventions to address poverty,
      stigma, discrimination and disclosure should be integrated with group-based ART
      adherence models in Vredenburg while further quantitative investigations should
      be carried out to quantify the extent to which these factors impede adherence in
      the community.

PMID- 29568619
TI  - Knowledge and practice of condom use as well as perceived barriers among street
      adolescents in Cameroon.
AB  - Introduction: Street children in Cameroon are adolescents, vulnerable to sexually
      transmitted infections (STIs) and HIV and/or AIDS. The level of knowledge and
      practice of condom use among this population is unknown. Objective of the study:
      To assess the knowledge, practice and barriers to condom use in Cameroon.
      Materials and methods: The study was an analytical cross-sectional survey
      conducted in 2015. Questionnaires were administered to street children in a quiet
      location. Recruitment was made using the snowball technique with the help of
      peers. Results: More than 90% of participants knew of condoms, but only about 6%
      reported to have used a condom during their last sexual encounter. Most of the
      participants did not know that condoms could prevent HIV; only a few (15.5%) knew
      about this. Conclusion: Street adolescents in Cameroon seem to know about
      condoms, but have insufficient information on the importance of their regular
      use. The main barriers for the low practice of condom use reported by this
      population were the following: condoms hinder sexual pleasure; are costly; and it
      is embarrassing to buy, use or propose to use a condom.

PMID- 29568620
TI  - Reported health, lifestyle and clinical manifestations associated with HIV status
      in people from rural and urban communities in the Free State Province, South
      Africa.
AB  - Background: HIV infection impacts heavily on the infected individual's overall
      health status. Aim: To determine significant health, lifestyle (smoking and
      alcohol use) and independent clinical manifestations associated with HIV status
      in rural and urban communities. Methods: Adults aged between 25 and 64 years
      completed a questionnaire in a structured interview with each participant. Blood
      specimens were analysed in an accredited laboratory using standard techniques and
      controls. Anthropometric measurements were determined using standardised methods.
      Results: Of the 567 rural participants, 97 (17.1%) were HIV-infected, and 172
      (40.6%) of the 424 urban participants. More than half of HIV-infected rural
      participants used alcohol and more than 40% smoked. Median body mass index (BMI)
      of HIV-infected participants was lower than that of uninfected participants.
      Significantly more HIV-infected participants reported experiencing cough (rural),
      skin rash (urban), diarrhoea (rural and urban), vomiting (rural), loss of
      appetite (urban) and involuntary weight loss (rural). Significantly more HIV
      uninfected participants reported diabetes mellitus (urban) and high blood
      pressure (rural and urban). In rural areas, HIV infection was positively
      associated with losing weight involuntarily (odds ratio 1.86), ever being
      diagnosed with tuberculosis (TB) (odds ratio 2.50) and being on TB treatment
      (odds ratio 3.29). In the urban sample, HIV infection was positively associated
      with having diarrhoea (odds ratio 2.04) and ever being diagnosed with TB (odds
      ratio 2.49). Conclusion: Involuntary weight loss and diarrhoea were most likely
      to predict the presence of HIV. In addition, present or past diagnosis of TB
      increased the odds of being HIV-infected. Information related to diarrhoea,
      weight loss and TB is easy to obtain from patients and should prompt healthcare
      workers to screen for HIV.

PMID- 29568621
TI  - Attitude shifts and knowledge gains: Evaluating men who have sex with men
      sensitisation training for healthcare workers in the Western Cape, South Africa.
AB  - Background: Men who have sex with men (MSM) in South Africa experience
      discrimination from healthcare workers (HCWs), impeding health service access.
      Objectives: To evaluate the outcomes of an MSM sensitisation training programme
      for HCWs implemented in the Western Cape province (South Africa). Methods: A
      training programme was developed to equip HCWs with the knowledge, awareness and
      skills required to provide non-discriminatory, non-judgemental and appropriate
      services to MSM. Overall, 592 HCWs were trained between February 2010 and May
      2012. Trainees completed self-administered pre- and post-training questionnaires
      assessing changes in knowledge. Two-sample t-tests for proportion were used to
      assess changes in specific answers and the Wilcoxon rank-sum test for overall
      knowledge scores. Qualitative data came from anonymous post-training evaluation
      forms completed by all trainees, in combination with four focus group discussions
      (n = 28) conducted six months after their training. Results: Fourteen per cent of
      trainees had received previous training to counsel clients around penile-anal
      intercourse, and 16% had previously received training around sexual health issues
      affecting MSM. There was a statistically significant improvement in overall
      knowledge scores (80% - 87%, p < 0.0001), specifically around penile-anal
      intercourse, substance use and depression after the training. Reductions in
      negative attitudes towards MSM and increased ability for HCWs to provide non
      discriminatory care were reported as a result of the training. Conclusion: MSM
      sensitisation training for HCWs is an effective intervention to increase
      awareness on issues pertaining to MSM and how to engage around them, reduce
      discriminatory attitudes and enable the provision of non-judgemental and
      appropriate services by HCWs.

PMID- 29568622
TI  - Photosensitive disorders in HIV.
AB  - Photosensitive disorders are common, affecting up to 5% of HIV-positive patients.
      HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria
      cutanea tarda and nutritional disorders such as pellagra are also more common in
      patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is
      a unique photosensitive disorder which is associated with advanced HIV. It is
      important to be able to recognise these conditions and withdraw photosensitising
      medications wherever possible.

PMID- 29568623
TI  - Patients' recommendations for a patient-centred public antiretroviral therapy
      programme in eThekwini, KwaZulu-Natal.
AB  - Background: The South African antiretroviral therapy (ART) programme, which is in
      its second decade of existence, includes many successes and challenges. This
      study provides patients' recommendations to address the challenges they currently
      experience at four antiretroviral (ARV) clinics based in urban public hospitals
      in order to provide a patient-centred service. Objectives: To use patients'
      recommendations to develop intervention strategies to improve patients'
      experiences of the public ART programme. Method: A three-stage, sequential, mixed
      method study was implemented. Stage 1 recruited five patients from the four sites
      to formulate and test a structured questionnaire prior to data collection. Stage
      2 recruited a stratified random sample of 400 patients (100 from each hospital)
      to complete the administered structured questionnaire. Stage 3 purposively
      selected 12 patients (three from each of the four sites) to participate in in
      depth audio-recorded interviews using an interview schedule. Results: The 412
      patients prioritised six recommendations, which are as follows: waiting areas
      should be enclosed to protect patients from the elements (rain, sun, lightening,
      wind and cold); patients should not have to return their files to the main
      hospital or ARV clinic themselves; stable patients should collect their ARV drugs
      every three months; pharmacy opening and closing times should be revised to suit
      patients' needs; HIV-positive patient representatives should be elected at each
      ARV clinic to address patients' concerns and/or challenges to ensure that the
      programme could be more patient-centred and ARV clinic operating times should be
      extended to open later during weekdays and over weekends. Conclusion: Patients
      living with HIV have a valuable contribution to make in assessing service
      delivery and making recommendations to create a patient-centred healthcare
      environment, which will feasibly increase their adherence to ART.

PMID- 29568624
TI  - HIV and the histopathologist.
AB  - The practicing histopathologist is often a forgotten link in the management of
      HIV patients. This article aims to highlight the unique challenges faced by
      anatomical pathologists as well as focusing on the valuable contribution they can
      make to ensure prompt and accurate diagnoses that will ultimately benefit the
      patient.

PMID- 29568625
TI  - The neuromyelitis optica presentation and the aquaporin-4 antibody in HIV
      seropositive and seronegative patients in KwaZulu-Natal, South Africa.
AB  - Background: The association of the anti-aquaporin-4 (AQP-4) water channel
      antibody with neuromyelitis optica (NMO) syndrome has been described from various
      parts of the world. There has been no large study describing this association
      from southern Africa, an HIV endemic area. HIV patients often present with visual
      disturbance or features of a myelopathy but seldom both either simultaneously or
      consecutively. We report our experience of NMO in the era of AQP-4 testing in HIV
      positive and HIV-negative patients seen in KwaZulu-Natal, South Africa. Methods:
      A retrospective chart review was undertaken of NMO cases seen from January 2005
      to April 2016 in two neurology units serving a population of 7.1 million adults.
      The clinical, radiological and relevant laboratory data were extracted from the
      files and analysed. Results: There were 12 HIV-positive patients (mean age 33
      years), 9 (75%) were women and all 12 were black patients. Of the 17 HIV-negative
      patients (mean age 32 years), 15 (88%) were women and 10 (59%) were black people.
      The clinical features in the two groups ranged from isolated optic neuritis,
      isolated longitudinally extensive myelitis or combinations. Recurrent attacks
      were noted in six HIV-positive patients and six HIV-negative patients. The AQP-4
      antibody was positive in 4/10 (40%) HIV-positive patients and 11/13 (85%) HIV
      negative patients. The radiological changes ranged from longitudinal hyperintense
      spinal cord lesions and long segment enhancing lesions of the optic nerves. Three
      patients, all HIV-positive, had tumefactive lesions with incomplete ring
      enhancement. Conclusion: This study confirms the presence of AQP-4-positive NMO
      in southern Africa in both HIV-positive and HIV-negative patients. The
      simultaneous or consecutive occurrence of optic neuritis and myelitis in an HIV
      positive patient should alert the clinician to test for the AQP-4 antibody. It is
      important to recognise this clinical syndrome as specific therapy is available.
      We further postulate that HIV itself may act as a trigger for an autoimmune
      process.

PMID- 29568626
TI  - Prevention of mother-to-child transmission of HIV guidelines: Nurses' views at
      four primary healthcare facilities in the Limpopo Province.
AB  - Background: When new guidelines for existing programmes are introduced, it is
      often the clinicians tasked with the execution of the guidelines who bear the
      brunt of the changes. Frequently their opinions are not sought. In this study,
      the researcher interviewed registered nurses working in the field of the
      prevention of mother-to-child transmission (PMTCT) of human immunodeficiency
      virus (HIV) to gain an understanding of their perspectives on the changes
      introduced to the guidelines. The guideline changes in 2014 were to move from the
      World Health Organization (WHO) Option B to Option B + which prescribes lifelong
      antiretroviral therapy (ART) for all HIV-positive pregnant women regardless of
      CD4 cell count. Objective: To determine what the registered nurses' perspectives
      are on the PMTCT programme as implemented at four PHC facilities in the Limpopo
      Province. Method: For this qualitative investigation, a descriptive research
      design was implemented. The data were collected during semi-structured interviews
      with nurses from four primary healthcare facilities in the Limpopo Province of
      South Africa. Data were analysed using thematic analysis. Results: Challenges
      preventing effective implementation (e.g. increased workloads, viz. staff
      shortages; poor planning of training; equipment and medication shortages and long
      lead times; poor patient education) were identified. Conclusion: In spite of the
      successes of the PMTCT programme, considerable challenges still prevail; lack of
      patient education, poor facilities management and staff shortages could
      potentially influence the implementation of the PMTCT guidelines negatively.

PMID- 29568627
TI  - Non-disclosure of HIV-positive status to a partner and mother-to-child
      transmission of HIV: Evidence from a case-control study conducted in a rural
      county in Kenya.
AB  - Background: Many factors contribute to an enhanced risk of infant HIV
      acquisition, two of which may include failure of a mother to disclose her HIV
      positive status to her partner and exclusion of male partners in preventing
      mother-to-child transmission of HIV (PMTCT) interventions. To justify why HIV
      programmes need to integrate male partner involvement and partner disclosure, we
      need to establish an association between the two factors and infant HIV
      acquisition. Objective: To determine whether failure to disclose an HIV-positive
      status to a male partner is associated with increased risk of infant HIV
      acquisition, and whether part of the association is explained by exclusion of
      male partner in PMTCT programmes. Methods: Using a case-control study design, we
      identified a total of 180 mother-baby pairs with HIV-exposed infants. Thirty-six
      pairs with HIV-positive babies (cases) were compared to 144 pairs with HIV
      negative babies (controls) on whether the mothers had disclosed their HIV status
      to their partner in order to determine whether a disclosure or lack of it
      contributed to increased risk of mother-to-child transmission of HIV (MTCT). Each
      case pair was matched to four control pairs from the same facility. Results:
      Overall, 16.7% of mothers had not disclosed their HIV status to their partners,
      the proportion being significantly more among cases (52.8% vs. 7.6%, p < 0.001).
      Non-disclosure was significantly associated with infant HIV acquisition (aOR 9.8
      (3.0-26.3); p < 0.001) and male partner involvement partially mediated the effect
      of non-disclosure on infant HIV acquisition (indirect coefficient = 0.17, p <
      0.005). Conclusions: Failure of an HIV-positive woman to disclose her status to
      her male partner and exclusion of male partners in PMTCT programmes are two
      social factors that may curtail success of interventions towards the goal of
      eliminating MTCT.

PMID- 29568628
TI  - Empowering patients, empowering clinicians: How the lessons of HIV can inform
      chronic disease management across the primary healthcare system.

PMID- 29568629
TI  - Disseminated cutaneous histoplasmosis with laryngeal involvement in a setting of
      immune reconstitution inflammatory syndrome.
AB  - Introduction: Histoplasmosis is a systemic mycosis caused by the dimorphic fungus
      Histoplasma capsulatum. We report a case of disseminated cutaneous histoplasmosis
      with mucocutaneous involvement in an AIDS patient paradigmatic of the
      multifaceted nature of the disease, which is an expression of the immune
      reconstitution inflammatory syndrome (IRIS). Patient presentation: A 39-year-old
      man presented with a three month history of asymptomatic papules and nodules with
      necrotic centres involving the centrofacial region. The patient was diagnosed as
      being HIV-positive a month earlier and was commenced on antiretroviral treatment.
      Two weeks after the development of skin lesions, the patient complained of a sore
      throat and hoarseness of his voice. A fibre-optic laryngoscopy and biopsies of
      the skin, larynx and liver were performed. Management and outcome: The CD4 counts
      increased from 2 cells/uL to 124 cells/uL, whereas the viral load decreased from
      one million to less than 20 copies/mL. A fibre-optic laryngoscopy revealed a
      supraglottitis with ulceration on the epiglottis. Histology of the liver, larynx
      and sections of the skin demonstrated pandermal necrotising granulomatous
      inflammation. Grocott-Gomori methenamine silver and Periodic acid-Schiff (PAS)
      stains revealed a relative paucity of intracellular, narrow-neck budding fungal
      organisms. Culture findings confirmed the diagnosis of histoplasmosis. The
      patient was treated with intravenous amphotericin B for two weeks followed by
      oral itraconazole 100 mg twice a day, with an excellent response to treatment.
      Conclusion: We present this case to remind clinicians that disseminated
      histoplasmosis in AIDS patients may occur as an expression of IRIS. A sudden
      onset of hoarseness with cutaneous lesions in a patient with disseminated disease
      should alert one to possible laryngeal histoplasmosis. Prompt recognition and
      treatment will avert the potential fatal complications of this disease.

PMID- 29568630
TI  - Progress towards the 2020 targets for HIV diagnosis and antiretroviral treatment
      in South Africa.
AB  - Background: The UNAIDS targets for 2020 are to achieve a 90% rate of diagnosis in
      HIV-positive individuals, to provide antiretroviral treatment (ART) to 90% of HIV
      diagnosed individuals and to achieve virological suppression in 90% of ART
      patients. Objectives: To assess South Africa's progress towards the 2020 targets
      and variations in performance by province. Methods: A mathematical model was
      fitted to HIV data for each of South Africa's provinces, and for the country as a
      whole. Numbers of HIV tests performed in each province were estimated from
      routine data over the 2002-2015 period, and numbers of patients receiving ART in
      each province were estimated by fitting models to reported public and private ART
      enrolment statistics. Results: By the middle of 2015, 85.5% (95% CI: 84.5% -
      86.5%) of HIV-positive South African adults had been diagnosed, with little
      variation between provinces. However, only 56.9% (95% CI: 55.3% - 58.7%) of HIV
      diagnosed adults were on ART, with this proportion varying between 50.8% in North
      West and 72.7% in Northern Cape. In addition, 78.4% of adults on ART were virally
      suppressed, with rates ranging from 69.7% in Limpopo to 85.9% in Western Cape.
      Overall, 3.39 million (95% CI: 3.26-3.52 million) South Africans were on ART by
      mid-2015, equivalent to 48.6% (95% CI: 46.0% - 51.2%) of the HIV-positive
      population. ART coverage varied between 43.0% in Gauteng and 63.0% in Northern
      Cape. Conclusion: Although South Africa is well on its way to reaching the 90%
      HIV diagnosis target, most provinces face challenges in reaching the remaining
      two 90% targets.

PMID- 29568631
TI  - HIV epidemic drivers in South Africa: A model-based evaluation of factors
      accounting for inter-provincial differences in HIV prevalence and incidence
      trends.
AB  - Background: HIV prevalence differs substantially between South Africa's
      provinces, but the factors accounting for this difference are poorly understood.
      Objectives: To estimate HIV prevalence and incidence trends by province, and to
      identify the epidemiological factors that account for most of the variation
      between provinces. Methods: A mathematical model of the South African HIV
      epidemic was applied to each of the nine provinces, allowing for provincial
      differences in demography, sexual behaviour, male circumcision, interventions and
      epidemic timing. The model was calibrated to HIV prevalence data from antenatal
      and household surveys using a Bayesian approach. Parameters estimated for each
      province were substituted into the national model to assess sensitivity to
      provincial variations. Results: HIV incidence in 15-49-year-olds peaked between
      1997 and 2003 and has since declined steadily. By mid-2013, HIV prevalence in 15
      49-year-olds varied between 9.4% (95% CI: 8.5%-10.2%) in Western Cape and 26.8%
      (95% CI: 25.8%-27.6%) in KwaZulu-Natal. When standardising parameters across
      provinces, this prevalence was sensitive to provincial differences in the
      prevalence of male circumcision (range 12.3%-21.4%) and the level of non-marital
      sexual activity (range 9.5%-24.1%), but not to provincial differences in condom
      use (range 17.7%-21.2%), sexual mixing (range 15.9%-19.2%), marriage (range 18.2%
      19.4%) or assumed HIV prevalence in 1985 (range 17.0%-19.1%). Conclusion: The
      provinces of South Africa differ in the timing and magnitude of their HIV
      epidemics. Most of the heterogeneity in HIV prevalence between South Africa's
      provinces is attributable to differences in the prevalence of male circumcision
      and the frequency of non-marital sexual activity.

PMID- 29568632
TI  - Delays in switching patients onto second-line antiretroviral treatment at a
      public hospital in eThekwini, KwaZulu-Natal.
AB  - Background: South Africa has one of the largest antiretroviral treatment (ART)
      programmes globally. In addition to increasing access to ART, it is important
      that the health system also focuses on the appropriate management of patients who
      fail first-line ART. Delays in switching patients onto second-line ART can
      adversely affect patient outcomes. Aim: To identify the patient-related and
      programmatic factors that delay switching patients onto second-line ART, and to
      assess whether these delays contribute to subsequent virological failure.
      Methods: Clinical records of adult patients switched onto second-line ART between
      2011 and 2014 at a public antiretroviral clinic were used to collect demographic,
      clinical, laboratory and programmatic data (availability of viral load results,
      inadequate patient follow-up, insufficient notes for effective follow-up). Data
      were analysed using univariate and multivariate logistic regression. Results: The
      median duration from the date of first and confirmatory documented high viral
      load (VL > 1000 copies/mL) to being switched to second-line ART was 13.2 months
      [interquartile range (IQR) 1.1-52.7 months] and 6.4 months (IQR 0-43.3 months),
      respectively. Inadequate prescriber notes for appropriate follow-up (p = 0.01)
      and unavailability of patients' viral load results (p = 0.02) were significantly
      associated with delays in switching to second-line ART. There was no significant
      association between the time taken to switch to second-line ART and subsequent
      virological failure. Conclusion: We observed lengthy delays in switching patients
      to second-line ART. Modifiable programmatic factors were found to be
      significantly associated with delays in switching to second-line ART.

PMID- 29568633
TI  - Actions of female sex workers who experience male condom failure during
      penetrative sexual encounters with clients in Cape Town: Implications for HIV
      prevention strategies.
AB  - Background: Condom failure has always been found to coexist with condom usage,
      especially among sex workers. Objective: To describe the actions of female sex
      workers when they are faced with situations of condom failure. Methods: Using the
      survey design, the participants were selected through the snowball sampling
      method. Their responses were obtained using a structured questionnaire. A total
      of 100 questionnaires were analysed. Results: With respect to the immediate
      actions of sex workers after condom failure, 36% of the respondents continued
      with the sexual encounter after noticing that the condom was broken. Another 36%
      stopped immediately when they noticed that the condom had failed, but replaced
      the condom; 13% of the participants stopped the sexual encounter completely; 3%
      applied vaginal spermicidal foam; and 5% of the respondents stopped immediately
      and took a douche when they had the chance. For the actions within the next 24
      hours of experiencing condom failure with a client, 53% of the participants did
      nothing; 4% sought counsel from a professional; 3% of the respondents took
      alcohol or drugs to forget the incident, 25% went to the clinic for assistance
      and 8% offered other responses. Conclusion: While continuing the sexual encounter
      without replacing the condom, taking alcohol and drugs or doing nothing could
      increase the risk of contracting HIV; however, actions like stopping the sexual
      encounter completely and visiting a clinic or a professional could make a
      difference between staying HIV negative or seroconverting. There is a need for
      targeted intervention to address issues of inappropriate behaviours after
      experiencing condom failure.

PMID- 29568634
TI  - Patient and provider attitudes to emergency department-based HIV counselling and
      testing in South Africa.
AB  - Background: The national South African HIV Counselling and Testing (HCT)
      guidelines mandate that voluntary counselling and testing (VCT) should be offered
      in all healthcare facilities. Emergency departments (EDs) are at the forefront of
      many healthcare facilities, yet VCT is not routinely implemented in this setting.
      Methods: We conducted a cross-sectional study that surveyed patients and
      healthcare providers at a tertiary care ED in the spring and summer of 2016 to
      ascertain their attitudes to VCT in the ED. We also used two previously validated
      survey instruments to gather data on patients' HIV knowledge and providers'
      stigma against patients living with HIV, as we anticipated that these may have an
      impact on providers' and patients' attitudes to the provision of HIV testing
      within the ED, and may offer insights for future intervention development.
      Results: A total of 104 patients and 26 providers were enrolled in the study.
      Overall, patients responded more favourably to ED-based HIV testing (92.3%)
      compared to providers (only 40% responded favourably). When asked about potential
      barriers to receiving or providing HIV testing, 16.4% of patients and 24% of
      providers felt that the subject of HIV was too sensitive and 58.7% of patients
      and 80% of providers indicated that privacy and confidentiality issues would pose
      major barriers to implementing ED-based HIV testing. Conclusion: This study shows
      that while ED-based HIV testing is overall highly acceptable to patients,
      providers seem less willing to provide this service. The survey data also suggest
      that future development of ED-based testing strategies should take into
      consideration privacy and confidentiality concerns that may arise within a busy
      emergency care setting. Furthermore, every effort should be made to tackle HIV
      stigma among providers to improve overall attitudes towards HIV-positive
      individuals that present for care in the ED.

PMID- 29568635
TI  - Condom migration after introduction of pre-exposure prophylaxis among HIV
      uninfected adolescents in South Africa: A cohort analysis.
AB  - Background: Approximately 3 million adolescents and young adults (AYA), between
      the ages of 15 years and 24 years, are living with HIV in sub-Saharan Africa. The
      use of pre-exposure prophylaxis (PrEP) may be a promising HIV prevention tool to
      bridge the high-risk years of AYA between sexual debut and adulthood. Objectives:
      Concerns have been raised that the use of PrEP could lead to an increase in
      sexual risk behaviour and sexually transmitted infections in general and less
      condom use in particular among adolescents. Methods: This study assesses condom
      use among South African adolescents enrolled on a demonstration PrEP study,
      called Pluspills, being conducted in Cape Town and Soweto. A questionnaire on
      sexual risk behaviour was administered at baseline and after 4, 8 and 12 weeks.
      Three different questions on condom use were asked at each visit. Unless all
      answers indicated condom use at all times, a participant was scored 'at risk'.
      McNemar's tests and a Cochran's Q test were used to investigate changes in condom
      use over time. Results: We interviewed 148 adolescents (66% female) at baseline.
      Eighty-nine participants completed all visits. In this group, an increase in
      condom use was observed over the period of 12 weeks. Most participants who
      reported behavioural changes mentioned an increase in condom use. Conclusion:
      There was no sign of sexual risk compensation in the 12 weeks of the study.
      Observed increase in condom use can be explained by an increased awareness of
      personal HIV risk or by social desirability or recall biases. In future research,
      additional data including other biomarkers of unprotected sex and longer follow
      up time would be useful to help understand the relationship between PrEP use,
      sexual risk perception and consequent behaviours, especially in adolescents.

PMID- 29568636
TI  - Approach to acute kidney injury in HIV-infected patients in South Africa.
AB  - Background: HIV-infected patients have an increased risk of renal disease.
      Current first-line antiretroviral therapy contains tenofovir disoproxil fumarate
      (TDF), which has nephrotoxic potential, characterised by proximal tubular cell
      injury. This may result in acute kidney injury, chronic kidney disease or partial
      or complete Fanconi syndrome. Objectives: We reviewed the existing literature on
      acute kidney injury and TDF-associated nephrotoxicity with the aim of providing
      an approach to diagnosis and management, which is relevant to a general medical
      practitioner. Methods: We performed a broad literature search of biomedical
      databases including PubMed and ScienceDirect. Our search terms included, but were
      not limited to, 'tenofovir', 'nephrotoxicity', 'HIV', 'acute kidney injury' and
      'renal tubular acidosis'.Our aim was not to generate a systematic literature
      review with weighted evidence, but rather to provide a review of best practice
      from a variety of sources. Where published studies were not available from the
      above databases, we relied on relevant textbooks and professional guidelines.
      Results: Potential nephrotoxicity is not an impediment to the widespread use of
      TDF in treating HIV infection, because most patients will tolerate the medication
      well. However, patients with advanced disease, low body weight, advanced age, pre
      existing kidney disease and concomitant use of other nephrotoxic medications are
      at increased risk of adverse renal events and may develop severe complications if
      not appropriately managed. These risk factors are unfortunately common in
      patients initiating antiretroviral therapy in South Africa. Conclusion:
      Prevention of renal damage by means of careful screening and monitoring of high
      risk patients is of paramount importance. Increased awareness of this problem and
      knowledge of how to manage kidney disease should be emphasised for general
      medical practitioners who work with HIV-infected patients.

PMID- 29568637
TI  - Late stage presentation of HIV-positive patients to antiretroviral outpatient
      clinic in Zambia.
AB  - Background: The World Health Organization (WHO) and the Zambian Ministry of
      Health set out new guidelines on combination antiretroviral therapy (cART) in
      2013 expanding the eligibility criteria for patients with HIV. Objectives: The
      primary objective were to determine when cART was initiated in HIV-positive
      outpatients according to clinical and immunological criteria, and to identify
      what proportion of patients who were eligible for cART according to 2013 WHO and
      2013 Zambian cART guidelines were currently on cART. Methodology: This was a
      clinical audit of HIV-positive outpatients attending the cART clinic at Ndola
      Central Hospital in Ndola, Zambia, with retrospective cross-sectional chart
      review and survey design. Data were collected from clinical records and
      interviews with patients. Results: A total of 99% of patients eligible for cART
      according to 2013 guidelines were on treatment. Clinical staging of patients at
      initiated on cART (n = 206) was as follows: 28% clinical stage I, 21% clinical
      stage II, 36% clinical stage III and 15% clinical stage IV. The median CD4 count
      when patients were started on cART was 147 cells/mm3. Conclusion: The results
      show that a majority of patients were initiated on cART late in their disease
      course according to immunological (CD4 < 200 cell/mm3) and clinical criteria
      (stage III or IV). However, the vast majority of patients eligible for cART were
      currently on treatment. The late initiation of cART appears to be a result of
      late diagnosis of HIV.

PMID- 29568638
TI  - The Botsha Bophelo Adolescent Health Study: A profile of adolescents in Soweto,
      South Africa.
AB  - Background: Youth between the ages of 15 years to 24 years account for almost
      half of new HIV infections in South Africa. Objectives: To describe the study
      details of the Botsha Bophelo Adolescent Health Study (BBAHS) which was an
      investigation of HIV risk among adolescents living in Soweto, South Africa.
      Methods: Eligibility criteria for the BBAHS included being 14 years - 19 years
      old and living in one of the 41 identified formal and informal areas in the
      township of Soweto. A cross-sectional survey was developed between investigators
      and an adolescent community advisory board consisting of previously validated
      scales and original questions including demographics, sexual and reproductive
      health, health service utilisation and psychosocial behaviours. Results: Between
      2010 and 2012, interviewers administered surveys among 830 adolescents (57%
      females), whose median age was 17 years (Q1, Q3: 16, 18), and found that 43% of
      participants identified their ethnicity as Zulu, 52% reported high food
      insecurity, 37% reported at least one parent had died, 15% reported living in a
      shack and 83% identified as heterosexual. Over half of the participants (55%)
      reported ever having sex (49% of females and 64% of males), 11% of whom initiated
      sex at < 15 years of age (3% females and 21% males). Almost half (47%) reported
      ever testing for HIV, 3% (n = 12) of whom self-reported being HIV-positive and
      33% (n = 4) were on antiretroviral therapy. Conclusion: Our study highlights
      important individual, relational and structural level determinants of HIV risk
      for adolescent men and women growing up within HIV hyperendemic settings.

PMID- 29568639
TI  - HIV-associated neurocognitive disorder in a KwaZulu-Natal HIV clinic: A
      prospective study.
AB  - Introduction: HIV-associated neurocognitive disorder (HAND) is a consequence of
      HIV infection of the central nervous system. The prevalence ranges between 15%
      and 60% in different settings. Objectives: This prospective study determined the
      prevalence of HAND at a peri-urban HIV clinic in KwaZulu-Natal. Factors
      associated with HAND were examined, alternate neurocognitive tools were tested
      against the international HIV dementia scale (IHDS) score and an association
      between HAND and non-adherence to antiretroviral therapy (ART) was explored.
      Methods: Between May 2014 and May 2015, 146 ART-naive outpatients were assessed
      for HAND. IHDS score <= 10 established a diagnosis of HAND. Functional capacity
      was assessed using Eastern Cooperative Oncology Group (ECOG) score. Chi-squared
      test was used to identify risk factors for HAND. The get-up-and-go test (GUGT)
      and Center for Epidemiological Studies Depression scale - revised (CESD-r) were
      tested against the IHDS. HIV viral load done six months after initiating ART was
      used as a surrogate marker for adherence to ART. Results: The prevalence of HAND
      was 53%. In total, 99.9% of patients with HAND had no functional impairment. Age
      > 50 years old was associated with HAND (p = 0.003). There was no correlation
      between the GUGT, CESD-r and the IHDS score. HAND was not associated with non
      adherence (p = 0.06). Conclusions: While the prevalence of HAND is high, it is
      not associated with functional impairment which suggests that asymptomatic
      neurocognitive impairment is prevalent. Age > 50 years old is a risk factor for
      HAND. The GUGT and CESD-r are not useful diagnostic tools for HAND. The
      relationship between HAND and non-adherence should be further explored.

PMID- 29568640
TI  - Multiple papular lesions in a patient with HIV and/or AIDS and coinfected with
      hepatitis B virus: Amyloidosis.
AB  - Introduction: The most common form of systemic amyloidosis is amyloid A induced
      by a chronic inflammation. In HIV-infected patients, elevated serum amyloid A
      levels might be associated with chronic inflammation. Patient presentation: A 43
      year-old male patient was admitted to hospital with a complaint of papular
      lesions around his eyes, existing for four months. The patient is receiving
      antiretroviral therapy. HIV RNA was undetectable, and the CD4 count was 770
      cells/mm3. He suffered from a bladder carcinoma for four years. On examination,
      periocular, perioral and anogenital papules, papular lesions in the meatus of
      external auditory canal, and intranasal polyps were observed. Management:
      Microscopic examination of the biopsy material taken from the periocular lesion
      and then from perianal polyps revealed eosinophilic deposition, and stained
      positively by Congo red. Serum amyloid A level was negative. Antiretroviral
      therapy was continued. Conclusion: A rare form of amyloidosis in a patient with
      HIV and/or AIDS and coinfected with hepatitis B virus (HBV) was presented here
      with cutaneous and mucosal lesions.

PMID- 29568641
TI  - Efavirenz and neuropsychiatric effects.

PMID- 29568642
TI  - Herbal slimming formulations or remedies interact with antiretroviral therapy.

PMID- 29568643
TI  - South African HIV self-testing policy and guidance considerations.
AB  - The gap in HIV testing remains significant and new modalities such as HIV self
      testing (HIVST) have been recommended to reach key and under-tested populations.
      In December 2016, the World Health Organization (WHO) released the Guidelines on
      HIV Self-Testing and Partner Notification: A Supplement to the Consolidated
      Guidelines on HIV Testing Services (HTS) and urged member countries to develop
      HIVST policy and regulatory frameworks. In South Africa, HIVST was included as a
      supplementary strategy in the National HIV Testing Services Policy in 2016, and
      recently, guidelines for HIVST were included in the South African National
      Strategic Plan for HIV, sexually transmitted infections and tuberculosis 2017
      2022. This document serves as an additional guidance for the National HIV Testing
      Services Policy 2016, with specific focus on HIVST. It is intended for policy
      advocates, clinical and non-clinical HTS providers, health facility managers and
      healthcare providers in private and public health facilities, non-governmental,
      community-based and faith-based organisations involved in HTS and outreach,
      device manufacturers, workplace programmes and institutes of higher education.

PMID- 29568645
TI  - 'Scared of going to the clinic': Contextualising healthcare access for men who
      have sex with men, female sex workers and people who use drugs in two South
      African cities.
AB  - Background: Men who have sex with men (MSM), sex workers (SW) and people who use
      drugs (PWUD) are at increased risk for HIV because of multiple socio-structural
      barriers and do not have adequate access to appropriate HIV prevention, diagnosis
      and treatment services. Objective: To examine the context of access to healthcare
      experienced by these three 'Key Populations', we conducted a qualitative study in
      two South African cities: Bloemfontein in the Free State province and Mafikeng in
      the North West province. Method: We carried out in-depth interviews to explore
      healthcare workers' perceptions, beliefs and attitudes towards Key Populations.
      Focus group discussions were also conducted with members of Key Populations
      exploring their experiences of accessing healthcare. Results: Healthcare workers
      described their own attitudes towards Key Populations and demonstrated a lack of
      relevant knowledge, skills and training to manage the particular health needs and
      vulnerabilities facing Key Populations. Female SW, MSM and PWUD described their
      experiences of stigmatisation, and of being made to feel guilt, shame and a loss
      of dignity as a result of the discrimination by healthcare providers and other
      community. members. Our findings suggest that the uptake and effectiveness of
      health services amongst Key Populations in South Africa is limited by
      internalised stigma, reluctance to seek care, unwillingness to disclose risk
      behaviours to healthcare workers, combined with a lack of knowledge and
      understanding on the part of the broader community members, including healthcare
      workers. Conclusion: This research highlights the need to address the broader
      healthcare provision environment, improving alignment of policies and programming
      in order to strengthen provision of effective health services that people from
      Key Populations will be able to access.

PMID- 29568644
TI  - Adult antiretroviral therapy guidelines 2017.
AB  - These guidelines are intended as an update to those published in the Southern
      African Journal of HIV Medicine in 2014 and the update on when to initiate
      antiretroviral therapy in 2015. Since the release of the previous guidelines, the
      scale-up of antiretroviral therapy (ART) in southern Africa has continued. New
      antiretroviral drugs have become available with improved efficacy, safety and
      robustness. The guidelines are intended for countries in the southern African
      region, which vary between lower and middle income.

PMID- 29568646
TI  - Risky sexual behaviour and human immunodeficiency virus (HIV) and acquired immune
      deficiency syndrome (AIDS) among healthcare workers.
AB  - Background: South Africa is known to have one of the highest prevalence rates of
      human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS)
      globally, with one in seven healthcare workers being HIV-positive. An HIV
      positive healthcare workforce is less equipped to respond to the increasing
      spread of the epidemic. Objectives: Assessment of the factors contributing to
      high HIV prevalence rates among healthcare workers is important in planning the
      development of human resources. This review sought to identify and understand
      predominant risky sexual behaviours among healthcare workers in HIV and AIDS
      affected countries. Methods: This study reviewed articles focusing on sexual
      behaviour among healthcare workers. Major health science databases (e.g.
      ProQuest, Cochrane, PubMed and CINAHL) were searched for combinations of keywords
      including 'healthcare workers', 'risky sexual behaviour' and 'HIV and AIDS'.
      Articles from a range of countries met inclusion and exclusion criteria. Results:
      Findings of the study revealed three main contributing factors: unprotected sex,
      multiple sex partners and sexual violence. Sexual violence emerged as the
      dominant risk factor in the majority of the studies. Most research was conducted
      in developed countries where the HIV infection rate is much lower than it is in
      developing countries. Conclusion: More research needs to be conducted in
      developing countries and appropriate strategies should be implemented to reduce
      sexual violence among healthcare workers. Appropriate procedures on reporting
      sexual violence coupled with education on HIV and AIDS as well as influencing
      attitudes and belief systems could assist in reducing the spread of HIV and AIDS
      within the healthcare workforce while minimising the effect on patient care.

PMID- 29568647
TI  - Modelling the human immunodeficiency virus (HIV) epidemic: A review of the
      substance and role of models in South Africa.
AB  - We review key mathematical models of the South African human immunodeficiency
      virus (HIV) epidemic from the early 1990s onwards. In our descriptions, we
      sometimes differentiate between the concepts of a model world and its
      mathematical or computational implementation. The model world is the conceptual
      realm in which we explicitly declare the rules - usually some simplification of
      'real world' processes as we understand them. Computing details of informative
      scenarios in these model worlds is a task requiring specialist knowledge, but all
      other aspects of the modelling process, from describing the model world to
      identifying the scenarios and interpreting model outputs, should be
      understandable to anyone with an interest in the epidemic.

PMID- 29568648
TI  - Barriers to Diagnosis Access for Chagas Disease in Colombia.
AB  - Chagas disease is the leading cause of nonischemic cardiomyopathy in Latin
      America. Timely access to diagnosis and trypanocidal treatment and preventive
      tools for millions of infected people continues to be a challenge. The purpose of
      this study was to identify potential barriers for the diagnosis of Chagas disease
      in Colombia from the perspective of healthcare providers. Using a simultaneous
      mixed-methods study design, we analyzed trends in access to screening and
      diagnosis for Chagas disease in Colombia and assessed the national barriers to
      access. The main barriers to access at the national level included a limited
      governmental public health infrastructure for the diagnosis of Chagas disease and
      limited physician awareness and knowledge of the disease. Data indicate that 1.5%
      of total expected cases based on national prevalence estimates were reported. Few
      public health laboratories have the capacity to perform complementary tests for
      the diagnosis of Chagas disease and almost 6 months elapse between the requests
      of the tests and the confirmation of the disease. This study shows that infected
      people must overcome a number of barriers to achieve diagnosis. Reducing barriers
      to early diagnosis of Chagas disease is an important goal in the fight against
      the disease.

PMID- 29568649
TI  - Relation of Food Insecurity and Hemoglobin Level in Preschool Aged Children.
AB  - Background: The iron deficiency anemia is a worldwide public problem, especially
      in developing countries, related to increased body needs and inadequate supply of
      iron from the diet. Objective: To analyze the association of food insecurity with
      hemoglobin concentration and the prevalence of anemia in preschool aged children
      in the city of Taubate, Sao Paulo, Brazil. Methods: A cross-sectional study was
      conducted with 306 children of preschool age. The nutritional status was assessed
      according to hemoglobin level and anthropometric indicators. Socioeconomic data
      and Brazilian Household Food Insecurity Measurement Scale (EBIA) results were
      obtained from interview with parents. Results: The prevalence of anemia was
      around 19% of preschool aged children and 41.2% families presented food
      insecurity. The anthropometric indicators were not associated with food
      insecurity and even though the bivariate analysis demonstrated that mild food
      insecurity affects the hemoglobin level, after adjusting the multivariate model
      this association lost significance (p > 0.05). Conclusion: The prevalence of
      anemia of 19.2% and the household food insecurity was found among 42.2% of the
      population.

PMID- 29568650
TI  - Radical Gastrectomy: Still the Cornerstone of Curative Treatment for Gastric
      Cancer in the Perioperative Chemotherapy Era-A Single Institute Experience over a
      Decade.
AB  - Background and Objectives: Most gastric cancer patients now undergo perioperative
      chemotherapy (POCT) based on the MAGIC trial results. POCT consists of
      neoadjuvant chemotherapy (NACT) as well as postoperative adjuvant chemotherapy.
      This study assessed the applicability of perioperative chemotherapy and the
      impact of radical gastrectomy encompassing a detailed lymph-node resection on
      outcomes of gastric cancer. Methods: Medical and pathology records of all gastric
      carcinoma resections were reviewed from 2006 onwards. Pathological details,
      number of lymph-nodes resected, and proportion of involved nodes, reasons for
      nonadministration of NACT, complications, recurrence, and survival data were
      analysed. Results: Only twenty-eight (37.8%) out of 74 patients underwent NACT
      and only nine completed POCT. NACT was declined due to comorbidities/patient
      refusal n = 24, early stage n = 14, and emergency presentation n = 8. Patients
      receiving NACT were much younger. Anastomotic leaks, hospital-mortality, lymph
      node yield, and proportion of involved lymph-nodes were similar in both groups.
      Thirty-two patients died due to recurrence with lymph-node involvement heralding
      higher recurrence risk and much poorer survival (HR 2.66; p = 0.013). Conclusion:
      More than 60% patients with resectable gastric carcinoma did not undergo NACT.
      Radical gastrectomy with lymphadenectomy remained the cornerstone of treatment in
      this period.

PMID- 29568651
TI  - A Study of the Correlation between VEP and Clinical Severity in Children with
      Autism Spectrum Disorder.
AB  - Visual evoked potential (VEP) is a technique used to assess the brain's
      electrical response to visual stimuli. The aims of this study were to examine
      neural transmission within the visual pathway through VEP testing in preschool
      children with autism spectrum disorder (ASD) and compare it to age-matched
      controls, as well as search for a correlation between the VEP parameters and the
      symptoms of ASD. Participants were composed of ASD children (9 males) and
      typically developing children (8 males and 4 females), aged between 3 and 5
      years. Checkerboards were chosen as the pattern-reversal VEP. The clinical
      severity of ASD was assessed using the Autism Treatment Evaluation Checklist
      (ATEC) and the Vineland Adaptive Behavior Scales 2nd edition (VABS-II). Our
      findings demonstrated that children with ASD had significantly longer N145
      latency compared to the controls. A longer N145 latency correlated with a higher
      score of ATEC within the sensory/cognitive awareness subdomain. In addition, a
      slower N145 response was also associated with a lower VABS-II score within the
      socialization domain. The correlation between longer VEP latency and abnormal
      behaviors in children with ASD suggests a delayed neural communication within
      other neural circuits, apart from the visual pathway. These lines of evidence
      support the possibility of using VEP, along with clinical parameters, for the
      assessment of ASD severity.

PMID- 29568653
TI  - Molecular Detection of Brucella spp. from Milk of Seronegative Cows from Some
      Selected Area in Bangladesh.
AB  - Brucellosis is endemic in Bangladesh both in humans and in animals. A number of
      reasons complicate the diagnosis, as bovine brucellosis can be diagnosed by
      various serological tests. But the tests have a limitation; when the organism
      remains intracellular, the disease goes into chronic stage and the antibody
      titres may decline. The present study was conducted for isolation and detection
      of Brucella spp. by polymerase chain reaction (PCR) from seronegative cows. A
      total of 360 dairy cows from three geographical regions were screened
      serologically by Rose Bengal Plate Test (RBPT) where 24 samples were
      serologically positive and the rest of the samples were serologically negative.
      Among the 24 seropositive individuals, 11 were culture positive and 6 were
      culture positive from serologically negative dairy cows. The overall
      seroprevalence of brucellosis in cattle was 6.6% and in disease condition a
      higher prevalence was recorded in abortion (28.07%) followed by infertility
      (13.33%). To confirm the Brucella spp. in seronegative dairy cattle, the isolates
      were extracted and PCR was conducted, which produced 905 bp amplicon size of 6
      Brucella spp. from milk sample. So, for the detection or eradication of
      brucellosis, a bacteriological test and a PCR technique should be performed with
      the serological test of milk.

PMID- 29568652
TI  - Imagine the Superiority of Dry Powder Inhalers from Carrier Engineering.
AB  - Inhalation therapy has strong history of more than 4000 years and it is well
      recognized around the globe within every culture. In early days, inhalation
      therapy was designed for treatment of local disorders such as asthma and other
      pulmonary diseases. Almost all inhalation products composed a simple formulation
      of a carrier, usually alpha-lactose monohydrate orderly mixed with micronized
      therapeutic agent. Most of these formulations lacked satisfactory pulmonary
      deposition and dispersion. Thus, various alternative carrier's molecules and
      powder processing techniques are increasingly investigated to achieve suitable
      aerodynamic performance. In view of this fact, more suitable and economic
      alternative carrier's molecules with advanced formulation strategies are
      discussed in the present review. Furthermore, major advances, challenges, and the
      future perspective are discussed.

PMID- 29568654
TI  - Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of
      Randomized Controlled Trials.
AB  - Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely
      used medication in several countries, including Thailand. NSAIDs have been
      associated with hepatic side effects; however, the frequency of these side
      effects is uncertain. Aim of the Review: To systematically review published
      literature on randomized, controlled trials that assessed the risk of clinically
      significant hepatotoxicity associated with NSAIDs. Methods: Searches of
      bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted
      up to July 30, 2016, to identify randomized controlled trials of ibuprofen,
      naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin,
      celecoxib, and etoricoxib in adults with any disease that provide information on
      hepatotoxicity outcomes. Results: Among the 698 studies, 18 studies met the
      selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib,
      etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic
      evidence based on hepatotoxicity justification criteria. Of all the
      hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had
      the highest proportion, which ranged from 0.015 to 4.3 (*10-2), followed by
      celecoxib, which ranged from 0.13 to 0.38 (*10-2), and etoricoxib, which ranged
      from 0.005 to 0.930 (*10-2). Conclusion: Diclofenac had higher rates of
      hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly
      demonstrated as aminotransferase elevation, while liver-related hospitalization
      or discontinuation was very low.

PMID- 29568655
TI  - Posaconazole-Induced Adrenal Insufficiency in a Case of Chronic Myelomonocytic
      Leukemia.
AB  - Introduction: Posaconazole is an azole used in treatment and prophylaxis of a
      broad spectrum of fungal infections. Antifungals such as ketoconazole have been
      shown to cause primary adrenal insufficiency (AI) as a result of direct
      inhibition on the steroidogenesis pathway. There is only one reported case of
      primary AI induced by posaconazole in a patient with mucormycosis. We report a
      case of posaconazole-related primary AI. Case: A 63-year-old man with chronic
      myelomonocytic leukemia was admitted for fatigue and intermittent nausea and
      vomiting. He had recently discontinued prophylactic posaconazole 300 mg daily. He
      was assessed for AI with a morning cortisol of 1.9 mcg/dL followed by a failed
      cosyntropin stimulation (CS) test. Adrenocorticotropic hormone (ACTH) level was
      154.6 pg/mL with negative 21-hydroxylase antibodies. The patient's symptoms
      improved with initiation of hydrocortisone and fludrocortisone. One year after
      discontinuation of posaconazole, he underwent a repeat CS test which showed
      normal adrenal function with normal ACTH at 34.1 pg/mL. Conclusion: In this case,
      we demonstrate that prolonged use of posaconazole is associated with primary AI.
      As use of posaconazole increases, knowledge of the potential risk of AI is
      important and must be included in the differential diagnosis when these patients
      present with hypotension, hypoglycemia, and failure to thrive.

PMID- 29568656
TI  - Emotional Lability as a Unique Presenting Sign of Suspected Chronic Traumatic
      Encephalopathy.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by
      head trauma. Diagnosis of this disease is difficult as reliable biomarkers have
      not been established and often this clinical entity is underappreciated with poor
      recognition of its clinical presentations (Lenihan and Jordan, 2015). The
      definitive diagnosis of CTE is determined by identification of neurofibrillary
      tangles in the perivascular space around the sulci in postmortem tissue (McKee et
      al., 2015). However, performing brain biopsies searching for neurofibrillary
      tangles is not a feasible option for early diagnosis. Thus, diagnosis of
      suspected CTE in the living has been based on clinical suspicion using proposed
      research criteria of clinical presentations. In addition, neuroimaging techniques
      have shown some promise in assisting diagnosis. Clinically, CTE is more commonly
      known to be associated with memory impairment and executive function disorder
      (Stern et al., 2013). However, here, we present two unique cases of prior
      professional football players where behavioral changes were the first identifying
      factors in clinical presentation and discuss possible neuroimaging options to
      help with CTE diagnosis. Because behavioral changes can be mistaken for other
      neuropsychological diseases, recognizing differing clinical constellations is
      critical to early diagnosis, early intervention, and improving patient care in
      suspected CTE.

PMID- 29568657
TI  - Use of Extracorporeal Membrane Oxygenation in Postpartum Management of a Patient
      with Pulmonary Arterial Hypertension.
AB  - Current guidelines do not recommend pregnancy in patients with pulmonary arterial
      hypertension (PAH). This is due to the associated high mortality, which both
      dissuades PAH patients from becoming pregnant and encourages termination of
      pregnancy due to high maternal mortality risk. As a result, there is a lack of
      data and, consequently, there are only general guidelines available for
      management of pregnancy in PAH patients. Additionally, novel therapeutic
      strategies such as extracorporeal membrane oxygenation (ECMO), although used in
      the management of nonpregnant PAH patients as a bridge to lung transplantation,
      have not been used to treat cardiopulmonary collapse in pregnant PAH patients. In
      an attempt to bridge this paucity of data, we report the successful use of ECMO
      in resuscitation and management of a pregnant PAH patient who experienced
      cardiopulmonary collapse following a caesarian section.

PMID- 29568658
TI  - Surgical Management of a Giant Adrenal Pseudocyst: A Case Report and Review of
      the Literature in the Last Decade.
AB  - Adrenal pseudocysts are rare entities and occurred in the 5th and the 6th decades
      of life. They are discovered accidentally, while appearing with nonspecific
      clinical and imaging findings. We report a case of a 28-year-old woman presented
      in our Emergency Department complaining about upper abdomen pain. Computed
      tomography revealed a hypodense cystic lesion containing hyperdense material. The
      size of a mass was 11. 7 * 9.3 * 6.6 cm in diameter close to the pancreas, but
      the origin was from the left adrenal gland. The mass was excised with surgical
      laparotomy. Giant adrenal pseudocysts are rare entities. Final diagnosis usually
      confirmed with the pathology examination. Management of such adrenal lesions
      depends on the unique characteristics, the surgeon's experience, and local
      resources.

PMID- 29568659
TI  - Primary Nocardia Infection Causing a Fluorodeoxyglucose-Avid Right Renal Mass in
      a Redo Lung Transplant Recipient.
AB  - Immunosuppression after lung transplantation may increase susceptibility to
      opportunistic infection and is associated with early and delayed deaths in lung
      transplant recipients. Factors that may predispose lung transplant recipients to
      opportunistic bacterial and fungal infections include prolonged corticosteroid
      use, renal impairment, treatment of acute rejection, and post-transplant diabetes
      mellitus. We present a unique case of a 63-year-old woman with diabetes mellitus
      who underwent redo lung transplantation. Three years after her right-sided single
      redo lung transplant, she presented with right-sided abdominal pain, nausea, and
      vomiting. Upon examination, computed tomography showed a 4.5 * 3.3 cm
      heterogeneous, enhancing right renal mass with a patent renal vein. Magnetic
      resonance imaging confirmed a T1/T2 hypointense, diffusion-restricting, right mid
      renal mass that was fluorodeoxyglucose-avid on positron emission tomography. We
      initially suspected primary renal cell carcinoma. However, after a right
      nephrectomy, no evidence of neoplasia was observed; instead, a renal abscess
      containing filamentous bacteria was noted, raising suspicion for infection of the
      Nocardia species. Special stains confirmed a diagnosis of Nocardia renal abscess.
      Computed tomography of the chest and brain revealed no lesions consistent with
      infection. We initiated a long-term therapeutic regimen of anti-Nocardia therapy
      with imipenem and trimethoprim-sulfamethoxazole.

PMID- 29568660
TI  - A Case of Early Stage Bladder Carcinosarcoma in Late Recurrence of Urothelial
      Carcinoma after Transurethral Resection.
AB  - Carcinosarcomas of the urinary bladder are rare biphasic neoplasms, consisting of
      both malignant epithelial and malignant mesenchymal components, and the prognosis
      of this tumor is unfavorable in most patients with even possibility of resection
      of disease. A 77-year-old male with a history of transurethral resection (TUR) of
      urothelial carcinoma (UC) of the bladder and adjuvant intravesical chemotherapy
      with pirarubicin 10 years ago revisited our department with a gross hematuria.
      Cystoscopy demonstrated an approximately 2.5 cm nonpapillary tumor on the right
      wall of the bladder. Pelvic MRI showed the tumor without extending the base of
      the bladder wall. The tumor could be completely removed with TUR. The malignant
      epithelial elements consisted of high-grade UC and the majority of mesenchymal
      components were fibrosarcomatous differentiation based on immunohistochemical
      studies. The tumor could be pathologically also suspected to be an early stage on
      TUR specimens. Although he has received no additional intervention due to the
      occurrence of myocardial infarction at three weeks after the TUR, he has been
      alive with no evidence of recurrence of the disease 27 months after the TUR. Some
      early stages of bladder carcinosarcoma might have a favorable prognosis without
      aggressive treatments.

PMID- 29568661
TI  - Congenital Bladder Diverticulum in Adults: A Case Report and Review of the
      Literature.
AB  - A 37-year-old male patient presented to the emergency department with fever,
      gross hematuria, and irritative lower urinary tract symptoms. Investigations
      revealed the presence of a large left bladder diverticulum superior and lateral
      to the left ureteral orifice without bladder outlet obstruction. Bladder
      diverticula in adults almost always present in the setting of bladder outlet
      obstruction. The finding of a congenital bladder diverticulum in an adult
      represents a rare clinical entity.

PMID- 29568662
TI  - S-Nitroso-N-acetyl-L-cysteine ethyl ester (SNACET) and N-acetyl-L-cysteine ethyl
      ester (NACET)-Cysteine-based drug candidates with unique pharmacological profiles
      for oral use as NO, H2S and GSH suppliers and as antioxidants: Results and
      overview.
AB  - S-Nitrosothiols or thionitrites with the general formula RSNO are formally
      composed of the nitrosyl cation (NO+) and a thiolate (RS-), the base of the
      corresponding acids RSH. The smallest S-nitrosothiol is HSNO and derives from
      hydrogen sulfide (HSH, H2S). The most common physiological S-nitrosothiols are
      derived from the amino acid L-cysteine (CysSH). Thus, the simplest S-nitrosothiol
      is S-nitroso-L-cysteine (CysSNO). CysSNO is a spontaneous potent donor of nitric
      oxide (NO) which activates soluble guanylyl cyclase to form cyclic guanosine
      monophosphate (cGMP). This activation is associated with multiple biological
      actions that include relaxation of smooth muscle cells and inhibition of platelet
      aggregation. Like NO, CysSNO is a short-lived species and occurs physiologically
      at concentrations around 1 nM in human blood. CysSNO can be formed from CysSH and
      higher oxides of NO including nitrous acid (HONO) and its anhydride (N2O3). The
      most characteristic feature of RSNO is the S-transnitrosation reaction by which
      the NO+ group is reversibly transferred to another thiolate. By this way numerous
      RSNO can be formed such as the low-molecular-mass S-nitroso-N-acetyl-L-cysteine
      (SNAC) and S-nitroso-glutathione (GSNO), and the high-molecular-mass S-nitrosol-L
      cysteine hemoglobin (HbCysSNO) present in erythrocytes and S-nitrosol-L-cysteine
      albumin (AlbCysSNO) present in plasma at concentrations of the order of 200 nM.
      All above mentioned RSNO exert NO-related biological activity, but they must be
      administered intravenously. This important drawback can be overcome by lipophilic
      charge-free RSNO. Thus, we prepared the ethyl ester of SNAC, the S-nitroso-N
      acetyl-L-cysteine ethyl ester (SNACET), from synthetic N-acetyl-L-cysteine ethyl
      ester (NACET). Both NACET and SNACET have improved pharmacological features over
      N-acetyl-L-cysteine (NAC) and S-nitroso-N-acetyl-L-cysteine (SNAC), respectively,
      including higher oral bioavailability. SNACET exerts NO-related activities which
      can be utilized in the urogenital tract and in the cardiovascular system. NACET,
      with high oral bioavailability, is a strong antioxidant and abundant precursor of
      GSH, unlike its free acid N-acetyl-L-cysteine (NAC). Here, we review the chemical
      and pharmacological properties of SNACET and NACET as well as their analytical
      chemistry. We also report new results from the ingestion of S-[15N]nitroso-N
      acetyl-L-cysteine ethyl ester (S15NACET) demonstrating the favorable
      pharmacological profile of SNACET.

PMID- 29568663
TI  - Tissue-based metabolite profiling and qualitative comparison of two species of
      Achyranthes roots by use of UHPLC-QTOF MS and laser micro-dissection.
AB  - Achyranthes bidentata and Achyranthes aspera are saponin and steroid rich
      medicinal plants, used extensively for therapeutic treatments in Traditional
      Chinese Medicine (TCM) and Ayurveda. A. bidentata is reported to be one of the
      rare and extensively exploited medicinal plant species that face the issue of
      being endangered. Finding qualitative substitute with identical phyto
      constituents contributing to similar composition and pharmacological benefits
      will help in reducing the burden of exploitation of the natural habitats of such
      plants. In the present study, a comparative metabolite analysis of the whole drug
      and specific tissues isolated by laser micro-dissection (LMD) was carried out for
      both the selected species, by use of ultra-high performance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). The results of the
      study indicate that the cortex and the medullary ray tissues are rich in their
      content of steroidal and saponin constituents such as (25S)-inokosterone-20,22
      acetonide, ginsenoside Ro, bidentatoside II and achyranthoside B. Metabolite
      profiling of the whole tissues of both the species indicates presence of
      identical constituents. Thus, it is inferred that A. bidentata and A. aspera can
      be used as qualitative substitutes for each other.

PMID- 29568664
TI  - A liquid chromatography with tandem mass spectrometry method for quantitating
      total and unbound ceritinib in patient plasma and brain tumor.
AB  - A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem
      mass spectrometry method was developed and validated for the determination of
      total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma
      and brain tumor tissue samples. Sample preparation involved simple protein
      precipitation with acetonitrile. Chromatographic separation was achieved on a
      Waters ACQUITY UPLC BEH C18 column using a 4-min gradient elution consisting of
      mobile phase A (0.1% formic acid in water) and mobile phase B (0.1% formic acid
      in acetonitrile), at a flow rate of 0.4 mL/min. Ceritinib and the internal
      standard ([13C6]ceritinib) were monitored using multiple reaction monitoring mode
      under positive electrospray ionization. The lower limit of quantitation (LLOQ)
      was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib
      concentration range of 1-2000 nM in plasma. The intra- and inter-day precision
      and accuracy were within the generally accepted criteria for bioanalytical method
      (<15%). The method was successfully applied to assess ceritinib brain tumor
      penetration, as assessed by the unbound drug brain concentration to unbound drug
      plasma concentration ratio, in patients with brain tumors.

PMID- 29568665
TI  - Denaturation studies on bovine serum albumin-bile salt system: Bile salt
      stabilizes bovine serum albumin through hydrophobicity.
AB  - Protein denaturation is under intensive research, since it leads to neurological
      disorders of severe consequences. Avoiding denaturation and stabilizing the
      proteins in their native state is of great importance, especially when proteins
      are used as drug molecules or vaccines. It is preferred to add pharmaceutical
      excipients in protein formulations to avoid denaturation and thereby stabilize
      them. The present study aimed at using bile salts (BSs), a group of well-known
      drug delivery systems, for stabilization of proteins. Bovine serum albumin (BSA)
      was taken as the model protein, whose association with two BSs, namely sodium
      cholate (NaC) and sodium deoxycholate (NaDC), was studied. Denaturation studies
      on the pre-formed BSA-BS systems were carried out under chemical and physical
      denaturation conditions. Urea was used as the chemical denaturant and BSA-BS
      systems were subjected to various temperature conditions to understand the
      thermal (physical) denaturation. With the denaturation conditions prescribed
      here, the data obtained is informative on the association of BSA-BS systems to be
      hydrophobic and this effect of hydrophobicity plays an important role in
      stabilizing the serum albumin in its native state under both chemical and thermal
      denaturation.

PMID- 29568666
TI  - Insight into the interaction of inhaled corticosteroids with human serum albumin:
      A spectroscopic-based study.
AB  - It is well known that the safety and efficacy profile of an inhaled
      cortocosteroid (ICS) is influenced by the pharmacokinetic properties and
      associated pharmacodynamic effects of the drug. Freely circulating, protein
      unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed
      investigation of drug-protein interaction could be of great interest to
      understand the pharmacokinetic behaviour of corticosteroids and for the design of
      new analogues with effective pharmacological properties. In the present work, the
      interaction between some corticosteroids and human serum albumin (HSA) has been
      studied by spectroscopic approaches. UV-Vis spectroscopy confirmed that all the
      investigated corticosteroids can bind to HSA forming a protein-drug complex. The
      intrinsic fluorescence of HSA was quenched by all the investigated drugs, which
      was rationalized in terms of a static quenching mechanism. The thermodynamic
      parameters determined by the Van't Hoff analysis of the binding constants
      (negative DeltaH and DeltaS values) clearly indicate thathydrogen bonds and van
      der Waals forces play a major role in the binding process between albumin and
      betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a
      major role in stabilizing albumin-triamcinolone complexes.

PMID- 29568667
TI  - Effect of nonionic surfactants in release media on accelerated in-vitro release
      profile of sirolimus eluting stents with biodegradable polymeric coating.
AB  - It is a well-known fact that sirolimus (SRL) undergoes degradation process via
      hydrolysis in aqueous media, leading to incorrect assessment of drug amount and
      thus release characteristics of formulations. The main objective of the present
      study was to evaluate the effect of nonionic surfactants in media on in-vitro
      release profiles for sirolimus eluting stents (SES) coated with biodegradable
      polymeric matrix. Phosphate buffer and acetate buffer incorporating nonionic
      surfactants with varying concentrations were examined for adequate solubility and
      stability (by RP-HPLC). Good sink condition was achieved in phosphate buffer (at
      pH 4.0) with 1.0% Tween 20, 1.0% Brij 35% and 0.5% Brij 58. Hydrodynamic size (by
      DLS) and the micelle-water partition coefficient (P) with standard free energy of
      solubilization (?Gs degrees ) of drug were evaluated to get some understanding
      about the solubilization phenomena. About 80% of drug release during the period
      of 48 h was achieved in optimized drug release media which was 1.0% Tween 20 in
      phosphate buffer pH 4.0. The obtained accelerated SRL release profile in
      optimized medium correlated well with the real time in-vitro release in phosphate
      buffer (pH 7.4). Surface morphology changes (by SEM), changes in gravimetric
      weights and molecular weight change (by GPC) were examined before and after drug
      release to understand the drug release mechanism which explains that the polymer
      did not undergo degradation during the drug release.

PMID- 29568668
TI  - Electrooxidation of sulfanilamide and its voltammetric determination in
      pharmaceutical formulation, human urine and serum on glassy carbon electrode.
AB  - For the first time, sulfanilamide (SFD) was determined in otologic solution,
      human urine and serum by electroanalytical techniques on glassy carbon electrode
      (GCE). The cyclic voltammetry (CV) experiments showed an irreversible oxidation
      peak at +1.06 V in 0.1 mol/L BRBS (pH = 2.0) at 50 mV/s. Different voltammetric
      scan rates (from 10 to 250 mV/s) suggested that the oxidation of SFD on the GCE
      was a diffusion-controlled process. Square-wave voltammetry (SWV) method under
      optimized conditions showed a linear response to SFD from 5.0 to 74.7 MUmol/L (R
      = 0.999) with detection and quantification limits of 0.92 and 3.10 MUmol/L,
      respectively. The developed SWV method showed better results for detection limit
      and linear range than the chronoamperometry method. It has been successfully
      applied to determine SFD concentration in pharmaceutical formulation, human urine
      and serum samples with recovery close to 100%.

PMID- 29568669
TI  - Synthesis of curcuminoid-imprinted polymers applied to the solid-phase extraction
      of curcuminoids from turmeric samples.
AB  - A molecular imprinting polymer technique was successfully applied to
      precipitation polymerization by using styrene as a functional monomer,
      curcuminoids as templates, acetonitrile as a porogenic solvent, benzoyl peroxide
      as the initiator, and ethylene glycol dimethacrylate as the crosslinker. The
      effects of interaction on the adsorption capacity of the molecularly imprinted
      polymer (MIP) and non-imprinted polymer (NIP) were investigated. A comparison of
      the adsorption capacity for MIP and NIP indicated that the NIP had the lowest
      adsorption capacity. The curcuminoid-imprinted polymer (Cur-MIP) was synthesized
      from 0.0237 mmol of styrene, 47.0 g of acetonitrile, 1.0238 mmol of ethylene
      glycol dimethacrylate, 0.0325 mmol of curcuminoids, and 0.2480 mmol of benzoyl
      peroxide. A high-performance liquid chromatography method with fluorescence
      detection was developed and validated for various chromatographic conditions for
      the determination of the curcuminoids in turmeric samples. The sample solution
      was separated using the Cur-MIP via solid-phase extraction and analyzed on a
      Brownlee analytical C18 column (150 mm * 6 mm, 5 um) using an isocratic elution
      consisting of acetonitrile and 0.1% trichloroacetic acid (40:60, v/v). The flow
      rate was maintained at 1.5 mL/min. The fluorescence detector was set to monitor
      at lambdaex = 426 nm and lambdaem = 539 nm. The quantification limit values were
      found to be 16.66, 66.66, and 33.33 ug/L for curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin, respectively. Thus, we concluded that the Cur-MIP and high
      performance liquid chromatographic-fluorescence method could be applied to
      selective extraction and could be used as a rapid tool for the determination of
      curcuminoids in medicinal herbal extracts.

PMID- 29568670
TI  - Analysis of iodinated quorum sensing peptides by LC-UV/ESI ion trap mass
      spectrometry.
AB  - Five different quorum sensing peptides (QSP) were iodinated using different
      iodination techniques. These iodinated peptides were analyzed using a C18
      reversed phase HPLC system, applying a linear gradient of water and acetonitrile
      containing 0.1% (m/v) formic acid as mobile phase. Electrospray ionization (ESI)
      ion trap mass spectrometry was used for the identification of the modified
      peptides, while semi-quantification was performed using total ion current (TIC)
      spectra. Non-iodinated peptides and mono- and di-iodinated peptides (NIP, MIP and
      DIP respectively) were well separated and eluted in that order. Depending on the
      used iodination method, iodination yields varied from low (2%) to high (57%).

PMID- 29568671
TI  - How do accountability problems lead to maternal health inequities? A review of
      qualitative literature from Indian public sector.
AB  - Background: There are several studies from different geographical settings and
      levels on maternal health, but none analyzes how accountability problems may
      contribute to the maternal health outcomes. This study aimed to analyze how
      accountability problems in public health system lead to maternal deaths and
      inequities in India. Methods: A conceptual framework was developed bringing
      together accountability process (in terms of standard setting, performance
      assessment, accountability (or answerability, and enforceability) -an ongoing
      cyclical feedback process at different levels of health system) and determinants
      of maternal health to analyze the influence of the process on the determinant
      leading to maternal health outcomes. A scoping review of qualitative and mixed
      methods studies from public health sector in India was conducted. A narrative and
      interpretive synthesis approach was applied to analyze data. Results: An
      overarching influence of health system-related factors over non-health system
      related factors leading to maternal deaths and inequities was observed. A
      potential link among such factors was identified with gaps in accountability
      functions at all levels of health system pertaining to policy gaps or
      conflicting/discriminatory policies and political commitment. A large number of
      gaps were also observed concerning performance or implementation of existing
      standards. Inherent to these issues was potentially a lack of proper monitoring
      and accountability functions. A critical role of power was observed influencing
      the accountability functions. Conclusion: The narrative and interpretive
      synthesis approach allowed to integrate and reframe the relevant comparable
      information from the limited empirical studies to identify the hot spots of
      systemic flaws from an accountability perspective. The framework highlighted
      problems in health system beyond health service delivery to wider areas such as
      policy or politics justifying their relevance and importance in such analysis. A
      crucial message from the study pertains to a need to move away from the
      traditional concept of viewing accountability as a blame-game approach and a
      concern of limited frontline health workers towards a constructive and systemic
      approach.

PMID- 29568672
TI  - U.S. Hospital Employment of Foreign-Educated Nurses and Patient Experience: A
      Cross-Sectional Study.
AB  - Introduction: For over half a century, hospitals in the United States have
      actively recruited foreign-educated nurses (FENs) in response to nurse shortages
      in hospitals and nursing homes. Little attention has been paid to the quality of
      care in the United States related to employment of FENs. Aims: The purpose of
      this retrospective study was to determine whether employment of FENs in U.S.
      hospitals is associated with patient care experience. Method: This study used
      cross-sectional data from three sources in 425 hospitals in four large states to
      evaluate the relationship between patient perceptions of care and hospital
      employment of FENs. The study linked data from publicly reported patient
      experience of care surveys, nurse surveys, and administrative data using unique
      hospital identifiers common across the data sets. Results: Patient-reported care
      experience was found to be more negative in hospitals employing more FENs, after
      controls for other possible explanations. Each 10% increase in FENs was
      associated with a decrease in the percentage of patients who would recommend
      their hospital and a decrease in the percentage of patients giving favorable
      reports on five nursing-specific aspects of patient experience. Conclusions: The
      results of this study suggest that employment of substantial numbers of nurses
      educated outside the United States may have implications for quality of care. The
      findings suggest that research on the outcomes of transition programs for FENs
      would be useful to inform regulatory policies.

PMID- 29568673
TI  - Biological Interpretation of Model-Reference Adaptive Control in a Mass Action
      Kinetics Metabolic Pathway Model.
AB  - The usefulness of control theory to model robustness in metabolic pathways is
      limited because controller properties and their implications on pathway
      regulation are unclear. Using sphingolipid biosynthesis in response to single
      gene overexpression as a case study, we apply model-reference adaptive control
      (MRAC) to model regulation in a mass action kinetics pathway model and report on
      its properties. Tracking error between treated cells (plant) and wild type
      (reference) is reduced in 9 of 10 system variables compared to using mass action
      kinetics only. This result is robust when system parameters are perturbed.
      Furthermore, we interpret control dynamics to infer potential regulatory
      interactions. Some observations are consistent with independent studies on the
      effects of the same experimental treatment, while others represent novel
      hypotheses that may be tested to yield additional biological insight. The
      usefulness and interpretation of MRAC to model metabolic pathway regulation is
      shown where plant dynamics approach the reference.

PMID- 29568674
TI  - Hippocampal atrophy, asymmetry, and cognition in type 2 diabetes mellitus.
AB  - Introduction: Type 2 diabetes mellitus is associated with global and hippocampal
      atrophy and cognitive deficits, and some studies suggest that the right
      hippocampus may display greater vulnerability than the left. Methods: Hippocampal
      volumes, the hippocampal asymmetry index, and cognitive functioning were assessed
      in 120 nondemented adults with long duration type 2 diabetes. Results: The
      majority of the sample displayed left greater than right hippocampal asymmetry
      (which is the reverse of the expected direction seen with normal aging). After
      adjustment for age, sex, and IQ, right (but not left) hippocampal volumes were
      negatively associated with memory, executive function, and semantic fluency.
      These associations were stronger with the hippocampal asymmetry index and
      remained significant for memory and executive function after additional
      adjustment for global brain atrophy. Conclusions: We conclude that asymmetric
      hippocampal atrophy may occur in type 2 diabetes, with greater atrophy occurring
      in the right than the left hippocampus, and that this may contribute to cognitive
      impairment in this disorder. These cross-sectional associations require further
      verification but may provide clues into the pathogenesis of cognitive disorders
      in type 2 diabetes.

PMID- 29568675
TI  - Combined prediction of miR-210 and miR-374a for severity and prognosis of hypoxic
      ischemic encephalopathy.
AB  - Background and Aim: Hypoxic-ischemic encephalopathy (HIE) is a disorder featured
      by hypoxic and ischemic damages during the perinatal period and its high
      mortality (i.e., 15%-20%) could be partly attributed to late diagnosis.
      Therefore, miR-210 and miR-374a were investigated to find if they could improve
      the diagnostic values of S100B protein and neuron-specific enolase (NSE) for HIE.
      Methods: Altogether 167 HIE newborns and 82 healthy newborns were recruited, and
      their blood were sampled for determining the levels of biomarkers. Specifically,
      S100B protein and NSE levels were detected based on the enzyme-linked
      immunosorbent assay (ELISA) kit, while the expressions of miR-210 and miR-374a
      were quantified by quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR). Moreover, the receiver operating characteristic (ROC) curves were
      established to assess the diagnostic values of the above biomarkers for HIE.
      Finally, the correlation analysis between miR-210/miR-374 and Neonatal Behavioral
      Neurological Assessment (NBNA) scoring or Gesell intellectual development were
      also conducted. Results: The levels of miR-210, miR-374a, S100B protein, and NSE
      were significantly distinct between HIE patients and healthy newborns (p < .05).
      Besides, miR-210 (rs = .573), miR-374a (rs = .651), NSE level (rs = -.622), and
      S100B level (rs = -.55) were all, respectively, correlated with NBNA scoring with
      statistical significance (p < .05). Furthermore, it was revealed that the
      combined diagnosis of miR-210, miR-374a, S100B protein, and NSE could obtain the
      highest accuracy regarding pairs of mild HIE versus moderate HIE (AUC = 0.898),
      moderate HIE versus severe HIE (AUC = 0.922), mild HIE versus severe HIE (AUC =
      0.996), and HIE versus control (AUC = 0.960). More than that, the four molecules
      were also remarkably associated with Gesell intellectual development (p < .05).
      Conclusion: MiR-210 and miR-374a could help to elevate the diagnostic value and
      prognostic prediction of S100B protein and NSE for HIE.

PMID- 29568676
TI  - Maternal separation affects expression of stress response genes and increases
      vulnerability to ethanol consumption.
AB  - Introduction: Maternal separation is an early life stress event associated with
      behavioral alterations and ethanol consumption. We aimed to expand the current
      understanding on the molecular mechanisms mediating the impact of postnatal
      stress on ethanol consumption. Methods: In the first experiment (T1), some of the
      pups were separated from their mothers for 6 hr daily (Maternal Separation group 
      MS), whereas the other pups remained in the cage with their respective mothers
      (Control group - C). In the second experiment (T2), mice from both groups were
      subjected to the model of free-choice between water and sucrose solution or
      between water and ethanol solution. Maternal behavior was assessed at the end of
      T1. At the end of both T1 and T2, pups were subjected to the light/dark box
      behavioral test and blood corticosterone concentrations were analyzed. Results:
      Our maternal separation protocol led to intense maternal care and affected weight
      gain of the animals. The expression of stress response genes was altered with
      higher levels of Crh and Pomc being observed in the hypothalamus, and higher
      levels of Crhr1, Crhr2, Htr2a and lower levels of Nr3c1 and Htr1a being observed
      in the hippocampus after T1. At the end of T2, we observed higher levels of Avp
      and Pomc in the hypothalamus, and higher levels of Crhr1, Crhr2, Nr3c1, Slc6a4,
      Bdnf and lower levels of Htr1a in the hippocampus. Additionally, maternal
      separation increased vulnerability to ethanol consumption during adolescence and
      induced changes in anxiety/stress-related behavior after T2. Furthermore,
      voluntary ethanol consumption attenuated stress response and modified expression
      of reward system genes: enhancing Drd1 and Drd2, and reducing Gabbr2 in the
      striatum. Conclusion: Maternal separation induced behavioral changes and
      alterations in the expression of key genes involved in HPA axis and in the
      serotonergic and reward systems that are likely to increase vulnerability to
      ethanol consumption in adolescence. We demonstrated, for the first time, that
      ethanol consumption masked stress response by reducing the activity of the HPA
      axis and the serotonergic system, therefore, suggesting that adolescent mice from
      the MS group probably consumed ethanol for stress relieving purposes.

PMID- 29568677
TI  - Exploring cancer in LRRK2 mutation carriers and idiopathic Parkinson's disease.
AB  - Objectives: To compare the risk of non-skin cancer in LRRK2 mutation carriers and
      individuals with idiopathic Parkinson's disease (iPD), explore the age at which
      LRRK2 mutation carriers have cancer compared to iPD subjects, and clarify whether
      certain cancers are more closely associated with the LRRK2 mutation than iPD.
      Materials and Methods: Demographic data and cancer outcomes from 830 iPD patients
      and 103 LRRK2 mutation carriers (27 with PD) were retrospectively collected.
      Oncologic data were obtained from the Cancer Registry of Norway and included
      cancer type and age at cancer. All study participants were of Norwegian
      ethnicity. Results: LRRK2 mutation carriers have increased risk of non-skin
      cancer compared with iPD subjects (OR 2.09; 95% CI 1.16-3.77; p = .015). A
      significant association was found between the mutation and breast cancer in women
      (OR 4.58; 95% CI 1.45-14.51; p = .010). No other associations between harboring a
      LRRK2 mutation and specific cancer types were uncovered. Conclusion: LRRK2
      mutation carriers have an increased risk of non-skin cancer compared with iPD
      subjects, which was mainly driven by the association between harboring the
      mutation and breast cancer in women. The increased risk is likely independent of
      ethnicity.

PMID- 29568678
TI  - Nonequivalent modulation of corticospinal excitability by positive and negative
      outcomes.
AB  - Objective: The difference between positive and negative outcomes is important in
      trial-and-error decision-making processes and affects corticospinal excitability.
      This study investigated corticospinal excitability during the performance of
      trial-and-error decision-making tasks with varying competing behavioral outcomes.
      Methods: Each trial began with one of five colored circles presented as a cue.
      Each color represented a different reward probability, ranging from 10% to 90%.
      The subjects were instructed to decide whether to perform wrist flexion in
      response to the cue. Two seconds after the presentation of the cue, a reward
      stimulus (picture of a coin) or penalty stimulus (mauve circle) was randomly
      presented to the subject. If the picture of a coin appeared, the subjects
      received the coin after the experiment if they had performed wrist flexion, but
      not if they had not performed wrist flexion. If a mauve circle appeared, a coin
      was deducted from the total reward if the subjects had performed wrist flexion,
      but not if they had not performed wrist flexion. One second after the reward or
      penalty stimulus, transcranial magnetic stimulation was delivered to the primary
      motor cortex at the midpoint between the centers of gravity of the flexor carpi
      radialis (agonist) and extensor carpi radialis (antagonist) muscles. Results:
      Cumulative wrist flexions were positively correlated with reward probabilities.
      Motor evoked potential (MEP) amplitudes in agonist muscles were significantly
      higher when wrist flexion incurred a penalty than when it incurred a reward, but
      there was no difference in the MEP amplitudes of antagonist muscles. Conclusion:
      Positive and negative behavioral outcomes differentially altered behavior and
      corticospinal excitability, and unexpected penalties had a stronger effect on
      corticospinal excitability for agonist muscles.

PMID- 29568679
TI  - Immediate and late outcomes of stenting for severe extracranial internal carotid
      artery stenosis in octogenarian patients.
AB  - Background: Multiple studies suggest that internal carotid artery stenting can be
      performed safely in octogenarians with low periprocedural complication rates.
      However, great concern still exists as to whether these patients will gain long
      term benefits from this procedure given their advanced age and uncertain life
      expectancy. We decided to conduct a retrospective study to determine short-and
      long-term clinical outcomes and to analyze survival duration in this population.
      Methods and Results: Sixty-nine consecutive elderly patients with either
      symptomatic or asymptomatic stenosis >=70% underwent 86 procedures. Immediate and
      late outcomes, as well as survival data, were analyzed retrospectively. Mean age
      was 83.1 +/- 2.7 years. Mean survival was 49.3 +/- 10.1 months. A complete
      neurological assessment was obtained at 1 and 2 years in 100% of patients, at 3
      years in 90.7% of patients and at 5 years in 84.8% of patients. Two major and one
      minor ischemic strokes occurred during the periprocedural period. No death,
      myocardial infarction or intracranial hemorrhage was recorded. The mean follow-up
      period was 55.4 +/- 24.6 months. Four patients experienced a minimum of 1 year of
      follow-up, and the longest is 8 years. Among the patients with the longest follow
      up time, 6 had ischemic strokes, of which 2 were fatal. In total, 17 deaths
      occurred. Four patients experienced dementia without stroke. Survival at 3 and 5
      years was estimated to be 90% and 73%, respectively. Conclusion: This study
      demonstrated that stenting in octogenarians was safe and effective during the
      periprocedural period. Long-term follow-up showed a low rate of fatal and
      nonfatal stroke, and patients survived long enough to benefit from the procedure.
      However, it was associated with a relatively high rate of long-term event. Though
      carotid artery stenting is a minimally invasive procedure, it should still be
      performed with great caution and only in carefully selected patients. The present
      study suggested that in this age population, carotid artery stenting might be
      considered as a revascularization option.

PMID- 29568680
TI  - Action video gaming and the brain: fMRI effects without behavioral effects in
      visual and verbal cognitive tasks.
AB  - Introduction: In this functional magnetic resonance imaging (fMRI) study, we
      compared task performance together with brain activation in a visuospatial task
      (VST) and a letter detection task (LDT) between longtime action video gamers (N =
      14) and nongamers (N = 14) in order to investigate possible effects of gaming on
      cognitive and brain abilities. Methods: Based on previous research, we expected
      advantages in performance for experienced action video gamers accompanied by less
      activation (due to higher efficiency) as measured by fMRI in the frontoparietal
      attention network. Results: Contrary to these expectations, we did not find
      differences in overall task performance, nor in brain activation during the VST.
      We identified, however, a significantly different increase in the BOLD signal
      from a baseline task to the LDT in action video gamers compared with nongamers.
      This increased activation was evident in a number of frontoparietal regions
      including the left middle paracingulate cortex, the left superior frontal sulcus,
      the opercular part of the left inferior frontal gyrus, and the left and right
      posterior parietal cortex. Furthermore, we found increased activation in the
      triangular part of the left inferior frontal gyrus in gamers relative to
      nongamers when activation during the LDT was compared with activation during the
      VST. Conclusions: In sum, the expected positive relation between action video
      game experience and cognitive performance could not be confirmed. Despite their
      comparable task performance, however, gamers and nongamers exhibited clear-cut
      differences in brain activation patterns presumably reflecting differences in
      neural engagement, especially during verbal cognitive tasks.

PMID- 29568681
TI  - Role of sLOX-1 in intracranial artery stenosis and in predicting long-term
      prognosis of acute ischemic stroke.
AB  - Objective: The role of sLOX-1 in acute ischemic stroke still remains unclear.
      This study aims to demonstrate the value of sLOX-1 in evaluating degrees of
      intracranial artery stenosis and to predict prognosis in stroke. Methods: Two
      hundred and seventy-two patients were included in this study and basic data were
      collected within 72 hr on admission. We assessed the association between sLOX-1
      levels and stroke conditions in one-year duration. After adjusting for potential
      confounders, regression analyses were performed. Results: We found that sLOX-1
      levels were increased significantly in severe patients compared to the mild
      stroke group (p = .011). After adjusting confounders, sLOX-1 was associated with
      a poor functional outcome in patients with an adjusted OR of 2. 946 (95% CI,
      1.788-4.856, p < .001). There was also positive correlation between sLOX-1 levels
      and the degrees of intracranial artery stenosis in the different groups (p =
      .029). Conclusions: Our study demonstrated that sLOX-1 levels could be used to
      evaluate the severity of stroke and the degrees of intracranial artery stenosis.
      Furthermore, sLOX-1 could be exploited to predict the long-term functional
      outcome of stroke.

PMID- 29568682
TI  - Bombesin receptor subtype-3-expressing neurons regulate energy homeostasis
      through a novel neuronal pathway in the hypothalamus.
AB  - Objectives: Bombesin receptor subtype-3 (BRS-3) has been suggested to play a
      potential role in energy homeostasis. However, the physiological mechanism of BRS
      3 on energy homeostasis remains unknown. Thus, we investigated the BRS-3-mediated
      neuronal pathway involved in food intake and energy expenditure. Materials and
      Methods: Expression of BRS-3 in the rat brain was histologically examined. The
      BRS-3 neurons activated by refeeding-induced satiety or a BRS-3 agonist were
      identified by c-Fos immunostaining. We also analyzed expression changes in
      feeding-relating peptides in the brain of fasted rats administered with the BRS-3
      agonist. Results: In the paraventricular hypothalamic nucleus (PVH), dorsomedial
      hypothalamic nucleus (DMH), and medial preoptic area (MPA), strong c-Fos
      induction was observed in the BRS-3 neurons especially in PVH after refeeding.
      However, the BRS-3 neurons in the PVH did not express feeding-regulating
      peptides, while the BRS-3 agonist administration induced c-Fos expression in the
      DMH and MPA, which were not refeeding-sensitive, as well as in the PVH. The BRS-3
      agonist administration changed the Pomc and Cart mRNA level in several brain
      regions of fasted rats. Conclusion: These results suggest that BRS-3 neurons in
      the PVH are a novel functional subdivision in the PVH that regulates feeding
      behavior. As the MPA and DMH are reportedly involved in thermoregulation and
      energy metabolism, the BRS-3 neurons in the MPA/DMH might mediate the energy
      expenditure control. POMC and CART may contribute to BRS-3 neuron-mediated energy
      homeostasis regulation. In summary, BRS-3-expressing neurons could regulate
      energy homeostasis through a novel neuronal pathway.

PMID- 29568683
TI  - Chinese neurologists' perspective on intravenous thrombolysis for acute ischemic
      stroke.
AB  - Objectives: This study examined the neurologists' perspective toward intravenous
      thrombolysis for the treatment of acute ischemic stroke and the influencing
      factors in a Chinese Province. Methods: A cross-sectional study was conducted
      from 1 October 2014 to 31 January 2015. A total of 719 neurologists from 66
      hospitals in Hubei Province were included. A questionnaire was designed, and
      multivariable logistic regression models were used to identify the factors
      associated with the neurologists' perspective toward intravenous thrombolysis.
      Results: Among the responding neurologists, 67.3% reported using intravenous
      thrombolysis and 32.9% believed the treatment was unsafe. Approximately 51.4%
      reported deficits in their knowledge of intravenous thrombolysis and 45.8% felt
      unconfident about their ability to employ the treatment. The majority (90.1%)
      supported hospitals in performing intravenous thrombolysis for eligible patients.
      Their safety concern was associated with hospital grade (odds ratio[OR] = 2.3;
      95% confidence interval [CI], 1.4-3.7) and previous experiences with thrombolysis
      (OR = 3.1; 95% CI, 2.1-4.6). Their confidence was associated with their
      educational background (OR = 2.5; 95% CI, 1.3-4.5), knowledge mastery (OR = 10.4;
      95% CI, 6.6-16.3), and previous experiences with thrombolysis (OR = 3.3; 95% CI,
      2.1-5.3). Their attitudes were associated with gender (OR = 0.6; 95% CI, 0.3-1.0)
      and previous experiences with thrombolysis (OR = 4.9; 95% CI, 2.5-9.4).
      Conclusions: Most neurologists in Hubei Province, China, identified with
      intravenous thrombolysis for the treatment of acute ischemic stroke. However,
      they were weak in knowledge and lack confidence. Therefore, training, especially
      practical training, is needed to promote the use of thrombolysis in the region.

PMID- 29568684
TI  - Feedback from human posterior parietal cortex enables visuospatial category
      representations as early as primary visual cortex.
AB  - Introduction: Categorization is a fundamental cognitive process, whereby the
      brain assigns meaning to sensory stimuli. Previous studies have found category
      representations in prefrontal cortex and posterior parietal cortex (PPC).
      However, these higher-order areas lack the fine-scale spatial representations of
      early sensory areas, and it remains unclear what mechanisms enable flexible
      categorization based on fine-scale features. Methods: In this study, we decoded
      functional MRI signals and measured causal influences, across visual, parietal,
      and prefrontal cortex from participants performing categorization based on coarse
      or fine-scale spatial information in thirteen healthy adults. Results: We show
      that category information based on coarse discriminations was represented in the
      PPC, in the intraparietal sulcus region, IPS1/2, at an early stage of
      categorization trials, whereas representations of category information based on
      fine-scale discriminations formed later during interactions between IPS1/2 and
      primary visual cortex (V1). Specifically, when fine-scale discriminations were
      necessary, we decoded significant category information from V1 at an intermediate
      stage of trials and again from IPS1/2 at a late stage. IPS1/2 feedback was
      critical, because categorization performance improved as causal influence from
      IPS1/2 to V1 increased. Further, these mechanisms were plastic, as the
      selectivity of IPS1/2 and V1 responses shifted markedly with retraining to
      categorize the same stimuli into two new groups. Conclusions: Our findings
      suggest that reentrant processing between the PPC and visual cortex enables
      flexible abstraction of category information.

PMID- 29568685
TI  - Food-related salience processing in healthy subjects during word recognition:
      Fronto-parietal network activation as revealed by independent component analysis.
AB  - Background: The study aimed to isolate and localize mutually independent
      cognitive processes evoked during a word recognition task involving food-related
      and food-neutral words using independent component analysis (ICA) for
      continuously recorded EEG data. Recognition memory (old/new effect) involves
      cognitive subcomponents-familiarity and recollection-which may be temporally and
      spatially dissociated in the brain. Food words may evoke additional attentional
      salience which may interact with the old/new effect. Methods: Sixteen satiated
      female participants undertook a word recognition task consisting of an encoding
      phase (learning of presented words, 40 food-related and 40 food neutral) and a
      test phase (recognition of previously learned words and new words).
      Simultaneously recorded 64-channel EEG data were decomposed into mutually
      independent components using the Infomax algorithm in EEGLAB. The components were
      localized using single dipole fitting using a four-shell BESA head model. The
      resulting (nonartefactual) components with <15% residual variance were clustered
      across subjects using the kmeans algorithm resulting in five meaningful clusters
      localized to fronto-parietal regions. Repeated-measures anova was employed to
      test main effects (old/new and food relevance) and their interaction on cluster
      time courses. Results: Early task-relevant old/new effects were localized to the
      medial frontal gyrus (MFG) and later old/new effects to the right parietal
      regions (precuneus). Food-related (nontask-relevant) salience effects were
      localized to bilateral parietal regions (left precuneus and right postcentral
      gyrus). Food-related salience interacted with task relevance, the old/new effect
      in MFG being significant only for food-neutral words highlighting central the
      role of MFG as the converging site of endogenous and exogenous salience inputs.
      Conclusion: Our results indicate ICA to be a valid technique to decompose complex
      neurophysiological signals involving multiple cognitive processes and implicate
      the fronto-parietal network as an important attentional network for processing
      salience and task demands.

PMID- 29568686
TI  - Transthyretin familial amyloid polyneuropathy (TTR-FAP): Parameters for early
      diagnosis.
AB  - Background: Familial transthyretin amyloidosis is a life-threatening disease
      presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has
      a detrimental effect on treatment and prognosis. To facilitate diagnosis, we
      analyzed data patterns of patients with transthyretin familial amyloid
      polyneuropathy (TTR-FAP) and compared them to polyneuropathies of different
      etiology for clinical and electrophysiological discriminators. Methods: Twenty
      four patients with TTR-FAP and 48 patients with diabetic polyneuropathy (dPNP)
      were investigated (neurological impairment score NIS; neurological disability
      score NDS) in a cross-sectional design. Both groups were matched for gender and
      presence of pain. Quantitative sensory testing (QST), sympathetic skin response
      (SSR), heart rate variability (HRV), and nerve conduction studies (NCV) were
      performed. Both groups were compared using univariate analysis. In a stepwise
      discriminant analysis, discriminators between both neuropathies were identified.
      These discriminators were validated comparing TTR-FAP patients with a cohort of
      patients with chemotherapy-induced polyneuropathy (CIN) and chronic inflammatory
      demyelinating neuropathy (CIDP). Results: TTR-FAP patients scored higher in NDS
      and NIS and had impaired cold detection (CDT, p = .024), cold-warm discrimination
      (TSL, p = .019) and mechanical hyperalgesia (MPT, p = .029) at the hands, SSR
      (upper limb, p = .022) HRV and ulnar and sural NCS (all p < .05) were more
      affected in TTR-FAP. Ulnar nerve sensory NCV, CDT, and the MPT but not the other
      parameters discriminated TTR-FAP from dPNP (82% of cases), from CIN (86.7%) and
      from CIDP (68%; only ulnar sNCV). Conclusion: Low ulnar SNCV, impaired cold
      perception, and mechanical hyperalgesia at the hands seem to characterize TTR-FAP
      and might help to differentiate from other polyneuropathies.

PMID- 29568687
TI  - Effects of gender, digit ratio, and menstrual cycle on intrinsic brain functional
      connectivity: A whole-brain, voxel-wise exploratory study using simultaneous
      local and global functional connectivity mapping.
AB  - Introduction: Gender and sex hormones influence brain function, but their effects
      on functional network organization within the brain are not yet understood.
      Methods: We investigated the influence of gender, prenatal sex hormones
      (estimated by the 2D:4D digit ratio), and the menstrual cycle on the intrinsic
      functional network organization of the brain (as measured by 3T resting-state
      functional MRI (rs-fMRI)) using right-handed, age-matched university students
      (100 males and 100 females). The mean (+/-SD) age was 20.9 +/- 1.5 (range: 18-24)
      years and 20.8 +/- 1.3 (range: 18-24) years for males and females, respectively.
      Using two parameters derived from the normalized alpha centrality analysis (one
      for local and another for global connectivity strength), we created mean
      functional connectivity strength maps. Results: There was a significant
      difference between the male mean map and female mean map in the distributions of
      network properties in almost all cortical regions and the basal ganglia but not
      in the medial parietal, limbic, and temporal regions and the thalamus. A
      comparison between the mean map for the low 2D:4D digit ratio group (indicative
      of high exposure to testosterone during the prenatal period) and that for the
      high 2D:4D digit ratio group revealed a significant difference in the network
      properties of the medial parietal region for males and in the temporal region for
      females. The menstrual cycle affected network organization in the brain, which
      varied with the 2D:4D digit ratio. Most of these findings were reproduced with
      our other datasets created with different preprocessing steps. Conclusions: The
      results suggest that differences in gender, prenatal sex hormone exposure, and
      the menstrual cycle are useful for understanding the normal brain and
      investigating the mechanisms underlying the variable prevalence and symptoms of
      neurological and psychiatric diseases.

PMID- 29568688
TI  - A low-cost multimodal head-mounted display system for neuroendoscopic surgery.
AB  - Background: With rapid advances in technology, wearable devices as head-mounted
      display (HMD) have been adopted for various uses in medical science, ranging from
      simply aiding in fitness to assisting surgery. We aimed to investigate the
      feasibility and practicability of a low-cost multimodal HMD system in
      neuroendoscopic surgery. Methods: A multimodal HMD system, mainly consisted of a
      HMD with two built-in displays, an action camera, and a laptop computer
      displaying reconstructed medical images, was developed to assist neuroendoscopic
      surgery. With this intensively integrated system, the neurosurgeon could freely
      switch between endoscopic image, three-dimensional (3D) reconstructed virtual
      endoscopy images, and surrounding environment images. Using a leap motion
      controller, the neurosurgeon could adjust or rotate the 3D virtual endoscopic
      images at a distance to better understand the positional relation between lesions
      and normal tissues at will. Results: A total of 21 consecutive patients with
      ventricular system diseases underwent neuroendoscopic surgery with the aid of
      this system. All operations were accomplished successfully, and no system-related
      complications occurred. The HMD was comfortable to wear and easy to operate.
      Screen resolution of the HMD was high enough for the neurosurgeon to operate
      carefully. With the system, the neurosurgeon might get a better comprehension on
      lesions by freely switching among images of different modalities. The system had
      a steep learning curve, which meant a quick increment of skill with it. Compared
      with commercially available surgical assistant instruments, this system was
      relatively low-cost. Conclusions: The multimodal HMD system is feasible,
      practical, helpful, and relatively cost efficient in neuroendoscopic surgery.

PMID- 29568689
TI  - Both activated and less-activated regions identified by functional MRI
      reconfigure to support task executions.
AB  - Introduction: Functional magnetic resonance imaging (fMRI) has become very
      important for noninvasively characterizing BOLD signal fluctuations, which
      reflect the changes in neuronal firings in the brain. Unlike the activation
      detection strategy utilized with fMRI, which only emphasizes the synchronicity
      between the functional nodes (activated regions) and the task design, brain
      connectivity and network theory are able to decipher the interactive structure
      across the entire brain. However, little is known about whether and how the
      activated/less-activated interactions are associated with the functional changes
      that occur when the brain changes from the resting state to a task state. What
      are the key networks that play important roles in the brain state changes?
      Methods: We used the fMRI data from the Human Connectome Project S500 release to
      examine the changes of network efficiency, interaction strength, and fractional
      modularity contributions of both the local and global networks, when the subjects
      change from the resting state to seven different task states. Results: We found
      that, from the resting state to each of seven task states, both the activated and
      less-activated regions had significantly changed to be in line with, and
      comparably contributed to, a global network reconfiguration. We also found that
      three networks, the default mode network, frontoparietal network, and salience
      network, dominated the flexible reconfiguration of the brain. Conclusions: This
      study shows quantitatively that contributions from both activated and less
      activated regions enable the global functional network to respond when the brain
      switches from the resting state to a task state and suggests the necessity of
      considering large-scale networks (rather than only activated regions) when
      investigating brain functions in imaging cognitive neuroscience.

PMID- 29568690
TI  - Altered functional connectivity in blepharospasm/orofacial dystonia.
AB  - Introduction: Blepharospasm is characterized by involuntary eyelid spasms. It can
      be associated with perioral dystonia (Meige's syndrome or orofacial dystonia). We
      aimed at studying resting-state functional brain connectivity in these patients
      and its potential modulation by therapeutic botulinum toxin injections. Methods:
      We performed resting-state functional MRI and a region of interest-based analysis
      of functional connectivity in 13 patients with blepharospasm/Meige's syndrome in
      comparison to 13 healthy controls. Patients were studied before and 4 weeks after
      botulinum toxin treatment. Simultaneous facial electromyography was applied to
      control for involuntary facial movements. Results: Before botulinum toxin
      treatment, patients showed reduced functional connectivity between caudate and
      primary sensorimotor, somatosensory association and visual cortices as well as
      between putamen and parietal association cortex. Cerebellar areas displayed
      decreased functional connectivity to somatosensory and visual association
      cortices. On the cortical level, connectivity was reduced between the cingulate
      cortex and the primary sensorimotor/premotor and parietal association cortex,
      between premotor areas and the primary somatosensory cortices, and between the
      postcentral gyrus and temporoparietal, secondary somatosensory, cingular, and
      cerebellar regions. Botulinum toxin treatment modulated functional connectivity,
      especially between cerebellum and visual cortices. Conclusions: Patients with
      blepharospasm/Meige's syndrome show altered functional connectivity at rest in
      widespread brain regions including basal ganglia, cerebellar, primary/secondary
      sensorimotor, and visual areas. Functionally, this may reflect a predisposition
      for defective movement inhibition and sensorimotor integration. Botulinum toxin
      treatment could modulate brain connectivity in blepharospasm by altering visual
      and sensory input.

PMID- 29568691
TI  - Consistent hypersocial behavior in mice carrying a deletion of Gtf2i but no
      evidence of hyposocial behavior with Gtf2i duplication: Implications for Williams
      Beuren syndrome and autism spectrum disorder.
AB  - Introduction: Williams-Beuren syndrome (WBS) is a developmental disorder caused
      by hemizygous deletion of human chromosome 7q11.23. Hypersocial behavior is one
      symptom of WBS and contrasts with hyposociality observed in autism spectrum
      disorder (ASD). Interestingly, duplications of 7q11.23 have been associated with
      ASD. The social phenotype of WBS has been linked to GTF2I or general
      transcription factor IIi (TFII-I). Duplication of GTF2I has also been associated
      with ASD. Methods: We compared mice having either a deletion (Gtf2i+/- ) or
      duplication (Gtf2i+/dup ) of Gtf2i to wild-type (Gtf2i+/+ ) littermate controls
      in a series of behavioral tasks including open-field activity monitoring,
      olfactory probes, a social choice task, social transmission of food preference,
      habituation-dishabituation, and operant social motivation paradigms. Results: In
      open-field observations, Gtf2i+/- and Gtf2i+/dup mice demonstrated normal
      activity and thigmotaxis, and surprisingly, each strain showed a significant
      preference for a stimulus mouse that was not observed in Gtf2i+/+ siblings. Both
      Gtf2i+/- and Gtf2i+/dup mice demonstrated normal olfaction in buried food probes,
      but the Gtf2i+/- mice spent significantly more time investigating urine scent
      versus water, which was not observed in the other strains. Gtf2i+/- mice also
      spent significantly more time in nose-to-nose contact compared to Gtf2i+/+
      siblings during the open-field encounter of the social transmission of food
      preference task. In operant tasks of social motivation, Gtf2i+/- mice made
      significantly more presses for social rewards than Gtf2i+/+ siblings, while there
      was no difference in presses for the Gtf2i+/dup mice. Discussion: Results were
      remarkably consistent across testing paradigms supporting a role for GTF2i in the
      hypersocial phenotype of WBS and more broadly in the regulation of social
      behavior. Support was not observed for the role of GTF2i in ASD.

PMID- 29568693
TI  - Acupuncture in the treatment of fatigue in Parkinson's disease: A pilot,
      randomized, controlled, study.
AB  - Introduction: Fatigue is a common and disabling problem in patients with
      Parkinson's disease (PD), and there is currently no satisfactory treatment. As
      acupuncture has been reported to be effective in fatigue related to other
      conditions, we sought to evaluate its efficacy in PD. Methods: This was a single
      center, randomized, sham-controlled study. Forty PD patients with moderately
      severe fatigue were randomized to receive 5 weeks of biweekly real or sham
      acupuncture. The primary outcome was change on the General Fatigue score of the
      Multidimensional Fatigue Inventory (MFI-GF) at 5 weeks. Secondary outcomes
      included MFI-Total score, Unified Parkinson's Disease Rating Scale Motor score
      (UPDRS Motor), Parkinson's Disease Questionnaire-39 (PDQ 39), Geriatrics
      Depression Scale (GDS), and Epworth Sleepiness Scale ESS). All outcome measures
      were evaluated at baseline, 5 and 9 weeks. Results: Both groups showed
      significant improvements in MFI-GF and MFI-Total scores at 5 and 9 weeks, but
      there were no significant between-group differences. There were no improvements
      from baseline for PDQ 39, GDS, and ESS. Although improvements were noted for the
      UPDRS Motor score in the real acupuncture group, no between-group difference
      could be demonstrated. Conclusions: Both real and sham acupuncture are equally
      effective in improving PD-related fatigue, and it is likely that this is due to
      nonspecific or placebo effects.

PMID- 29568692
TI  - Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive
      impairments at 17 months of age.
AB  - Introduction: Tau is a microtubule-associated binding protein implicated in
      neurodegenerative tauopathies, including frontotemporal dementia (FTD) and
      Alzheimer's disease (AD). These diseases result in the intracellular accumulation
      of hyperphosphorylated tau in the form of neurofibrillary tangles, the presence
      of which is associated with cognitive deficits. Methods: We conducted a
      longitudinal behavioral study to provide a profile of the TgTau(P301L)23027
      transgenic mouse in multiple cognitive domains across multiple ages. P301L is the
      tau mutation most frequently observed in patients with frontotemporal dementia
      with parkinsonism linked to chromosome 17 (FTDP-17) and this mouse model
      recapitulates the progressive development of glial and neurofibrillary tangles,
      and associated cerebral atrophy observed in patients. We examined frontal cortex
      dependent executive function and attention with the touchscreen 5-choice serial
      reaction time test (5-CSRTT) and assessed the function of temporal cortical
      structures using novel object recognition (OR). Results: Despite using sensitive
      tasks, there were no apparent changes in executive function, attention, or
      recognition memory in the transgenic mice from 5 to 17 months of age.
      Conclusions: This study represents the first comprehensive longitudinal analysis
      of cognition in the TgTauP301L mouse model and suggests that this model is not
      ideal for studying early attention and recognition memory impairments associated
      with tauopathy. However, spatial and object recognition memory impairments were
      observed during follow-up assessments when the mice were 18 and 21 months,
      respectively. These impairments are consistent with previous publications, and
      with a dementia-like phenotype in these mice when aged.

PMID- 29568694
TI  - Familial multiple sclerosis and association with other autoimmune diseases.
AB  - Objectives: Autoimmune diseases (AID) follow a complex, probably polygenic,
      pattern of inheritance and often cluster in families of patients with multiple
      sclerosis (MS). Our objective was to analyze family patterns and characteristics
      in families including more than one patient with MS. Materials and Methods: We
      analyzed personal and family history of neurological, systemic, and autoimmune
      diseases in 84 MS patients from 40 different families. Families were classified
      in two groups: families with cases of MS in at least two different generations
      (15 families) and families in which cases of MS belonged to only one generation
      (25 families). Results: The two previously established groups presented different
      clinical patterns and frequency of association with another AID. In one group,
      the second generation displayed a higher annual relapse rate than the first
      generation, higher frequency of progressive forms of MS, and more patients with
      another AID in addition to MS. Relapsing-remitting forms of MS (RRMS) were more
      frequent in the other group. Conclusions: Families that include more than one MS
      patient may show two distinct patterns. This finding seems important for the
      compression and analysis of genetic information on MS.

PMID- 29568695
TI  - Novel compound heterozygous mutations in the PARK2 gene identified in a Chinese
      pedigree with early-onset Parkinson's disease.
AB  - Objects: To capture point mutations and short insertions/deletions in 49
      previously reported genes associated with Parkinson's disease (PD) in a Chinese
      pedigree with early-onset Parkinson's disease (EOPD)-affected individuals.
      Methods: Clinical examinations and genomic analysis were performed on 21 subjects
      belonging to three generations of a Chinese family. Target region capture and
      high-throughput sequencing were used for screening 49 genes, which were
      previously reported to be associated with PD. The direct Sanger sequencing method
      in all subjects further verified the abnormal DNA fragments in the PARK2 gene.
      Results: Four family members, including a mother (I-1) and her three children (II
      2, II-3, and II-7), were diagnosed with PD by clinical manifestations and/or
      PET/CT imaging analyses. Novel compound heterozygous mutations, consisting of a
      fragment deletion in exon 1 to 2 (EX 1-2 del) and a splicing point mutation c.619
      1 (G > C) in the 6th intron of the PARK2 gene, were identified in II-2, II-3, and
      II-7. Individual EX 1-2 del or c.619-1 (G > C) mutations were detected in I-1 and
      the third generation (III-2, 3, 5, 10, and 11).Other mutations were not detected
      in the 49 known PD-associated genes. Conclusion: Novel compound heterozygous
      mutations were identified in a Chinese pedigree and might represent a cause of
      familial EOPD with autosomal dominant inheritance.

PMID- 29568696
TI  - Aplastic anemia secondary to nivolumab and ipilimumab in a patient with
      metastatic melanoma: a case report.
AB  - Background: Immune checkpoint blockade (ICB) is becoming an increasingly
      prevalent strategy in the clinical realm of cancer therapeutics. With more
      patients being administered ICB for a host of tumor types, the scope of adverse
      events associated with these drugs will likely grow. Here we report a case of
      aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB
      therapy. To our knowledge, this is only the second case of AA secondary to dual
      ICB in the literature, and the first to have a positive patient outcome. Case
      presentation: A 51-year old male with metastatic melanoma was started on dual
      immune checkpoint blockade, in the form ipilimumab (3 mg/kg) and nivolumab (1
      mg/kg). Two weeks following the second cycle, he presented to the emergency
      department with profound polypipsia, polyuria and fatigue. The patient was
      diagnosed with diabetic ketoacidosis secondary to immune therapy induced type-1
      diabetes and was admitted to the ICU. While in hospital the patient developed a
      symptomatic anemia and neutropenia. A bone marrow biopsy revealed a markedly
      hypocellular marrow with trinlineage hypoplasia with no evidence of
      myelodysplasia, neoplasm or excess blasts. Flow cytometry revealed an inverted
      CD4+:CD8+ ratio and an absence of hematogones. Taken together the presumed
      etiology was AA secondary to immunotherapy. The patient was subsequently started
      in IV methylprednisone 70 mg/day for 8 days, followed by a prednisone taper. This
      intervention rectified the bicytopenia and to date the patient has shown stable
      blood counts. Conclusion: With the use of ICBs becoming increasingly prevalent in
      the clinical arena, the number of patients presenting with immune-related adverse
      events will likely increase. The current case illustrates the need to be vigilant
      when managing cancer patients receiving ICB. The resolution of this patient's AA
      with corticosteroids highlights the value of early detection and appropriate
      treatment of these rare immune-mediated adverse events.

PMID- 29568698
TI  - When There Are Only Minorities: Identity and In-Group / Out-Group Orientations of
      Emerging Adults in Four South African Ethnocultural Groups.
AB  - Intergroup relation perspectives stem from research in Western contexts with
      clear distinctions between the dominant and nondominant groups. In South Africa,
      with at least 13 different cultural groups and 11 official languages, no group is
      dominant in all life spheres. We examine the relationship between identity and in
      /out-group orientation across Black-Zulu, Coloured (mixed racial ancestry),
      Indian, and White-Afrikaans emerging adults (N = 390; 75% females, Mage = 19.97
      years, SD = 2.44). Results indicate that personal identity for all groups and
      ethnic identity for Black-Zulu, Indian, and White-Afrikaans emerging adults were
      important for intergroup relations. Black-Zulu, Coloured, and Indian emerging
      adults distinguish themselves less from others, whereas White-Afrikaans emerging
      adults are less open to others. Ultimately, the complexity of intergroup
      relations in South Africa has implications for the effective transformation
      interventions needed to counter experiences of threat and make group boundaries
      more flexible for emerging adults.

PMID- 29568697
TI  - Intratympanic (IT) Therapies for Meniere's Disease: Some Consensus Among the
      Confusion.
AB  - Purpose of Review: Aminoglycosides and corticosteroids are commonly used to treat
      Meniere's disease. Intratympanic (IT) administration of these medications allows
      high inner ear concentrations without significant adverse systemic effects. As a
      direct result, IT therapy has grown in popularity. Recent studies have compared
      patient outcomes between IT aminoglycosides and corticosteroids. This review
      summarizes these findings. Recent Findings: Trials comparing IT corticosteroids
      to IT placebo or oral therapy have had conflicting results. Most recently,
      Lambert et al. investigated the effect of IT dexamethasone in a sustained-release
      formulation compared to placebo. Their findings demonstrated improvement in some
      secondary measures of vertigo with the sustained-release formulation.IT
      gentamicin is known to be effective in controlling vertigo in Meniere's disease.
      In a recent study from 2016, Patel et al compared IT gentamicin and IT
      methylprednisolone in a double-blind, randomized controlled trial and identified
      no significant differences between the two in vertigo control. Summary: IT
      injections of aminoglycosides and corticosteroids can improve vertigo control.
      Hearing and vestibular loss however may result with IT aminoglycosides.
      Corticosteroids demonstrate limited hearing loss but may not have the same
      efficacy in controlling vertigo. Further investigation in the etiology of
      Meniere's disease is needed to tailor the proposed treatment to suit the disease
      mechanism.

PMID- 29568699
TI  - Anticipatory Emotion in Schizophrenia.
AB  - While people with schizophrenia report experiencing as much emotion in the
      presence of emotionally evocative stimuli as do people without schizophrenia,
      evidence suggests that they have deficits in the anticipation of positive
      emotion. However, little is known about the anticipation of negative emotion in
      schizophrenia, thus leaving open whether anticipation deficits are more general.
      We sought to assess anticipation of positive and negative stimuli across multiple
      methods of measurement. We measured reported experience and emotion modulated
      startle response in people with (n = 27) and without (n = 27) schizophrenia as
      they anticipated and subsequently viewed evocative pictures. People with
      schizophrenia showed an overall dampened response during the anticipation of
      positive and negative stimuli, suggesting a more general deficit in anticipatory
      emotional responses. Moreover, anticipatory responses were related to symptoms
      and functioning in people with schizophrenia. Together, these findings point to
      important new directions for understanding emotion deficits in schizophrenia.

PMID- 29568700
TI  - Capturing patient-reported area of knee pain: a concurrent validity study using
      digital technology in patients with patellofemoral pain.
AB  - Background: Patellofemoral pain (PFP) is often reported as a diffuse pain at the
      front of the knee during knee-loading activities. A patient's description of pain
      location and distribution is commonly drawn on paper by clinicians, which is
      difficult to quantify, report and compare within and between patients. One way of
      overcoming these potential limitations is to have the patient draw their pain
      regions using digital platforms, such as personal computer tablets. Objective: To
      assess the validity of using computer tablets to acquire a patient's knee pain
      drawings as compared to paper-based records in patients with PFP. Methods:
      Patients (N = 35) completed knee pain drawings on identical images (size and
      colour) of the knee as displayed on paper and a computer tablet. Pain area
      expressed as pixel density, was calculated as a percentage of the total drawable
      area for paper and digital records. Bland-Altman plots, intraclass correlation
      coefficient (ICC), Pearson's correlation coefficients and one-sample tests were
      used in data analysis. Results: No significant difference in pain area was found
      between the paper and digital records of mapping pain area (p = 0.98), with the
      mean difference = 0.002% (95% CI [-0.159-0.157%]). A very high agreement in pain
      area between paper and digital pain drawings (ICC = 0.966 (95% CI [0.93-0.98], F
      = 28.834, df = 31, p < 0.001). A strong linear correlation (R2 = 0.870) was found
      for pain area and the limits of agreement show less than +/-1% difference between
      paper and digital drawings. Conclusion: Pain drawings as acquired using paper and
      computer tablet are equivalent in terms of total area of reported knee pain. The
      advantages of digital recording platforms, such as quantification and reporting
      of pain area, could be realized in both research and clinical settings.

PMID- 29568701
TI  - Reliability and concurrent validity of the iPhone(r) Compass application to
      measure thoracic rotation range of motion (ROM) in healthy participants.
AB  - Background: Several water-based sports (swimming, surfing and stand up paddle
      boarding) require adequate thoracic mobility (specifically rotation) in order to
      perform the appropriate activity requirements. The measurement of thoracic spine
      rotation is problematic for clinicians due to a lack of convenient and reliable
      measurement techniques. More recently, smartphones have been used to quantify
      movement in various joints in the body; however, there appears to be a paucity of
      research using smartphones to assess thoracic spine movement. Therefore, the aim
      of this study is to determine the reliability (intra and inter rater) and
      validity of the iPhone(r) app (Compass) when assessing thoracic spine rotation
      ROM in healthy individuals. Methods: A total of thirty participants were
      recruited for this study. Thoracic spine rotation ROM was measured using both the
      current clinical gold standard, a universal goniometer (UG) and the Smart Phone
      Compass app. Intra-rater and inter-rater reliability was determined with a
      Intraclass Correlation Coefficient (ICC) and associated 95% confidence intervals
      (CI). Validation of the Compass app in comparison to the UG was measured using
      Pearson's correlation coefficient and levels of agreement were identified with
      Bland-Altman plots and 95% limits of agreement. Results: Both the UG and Compass
      app measurements both had excellent reproducibility for intra-rater (ICC 0.94
      0.98) and inter-rater reliability (ICC 0.72-0.89). However, the Compass app
      measurements had higher intra-rater reliability (ICC = 0.96 - 0.98; 95% CI [0.93
      0.99]; vs. ICC = 0.94 - 0.98; 95% CI [0.88-0.99]) and inter-rater reliability
      (ICC = 0.87 - 0.89; 95% CI [0.74-0.95] vs. ICC = 0.72 - 0.82; 95% CI [0.21
      0.94]). A strong and significant correlation was found between the UG and the
      Compass app, demonstrating good concurrent validity (r = 0.835, p < 0.001).
      Levels of agreement between the two devices were 24.8 degrees  (LoA -9.5 degrees
      , +15.3 degrees ). The UG was found to consistently measure higher values than
      the compass app (mean difference 2.8 degrees , P < 0.001). Conclusion: This study
      reveals that the iPhone(r) app (Compass) is a reliable tool for measuring
      thoracic spine rotation which produces greater reproducibility of measurements
      both within and between raters than a UG. As a significant positive correlation
      exists between the Compass app and UG, this supports the use of either device in
      clinical practice as a reliable and valid tool to measure thoracic rotation.
      Considering the levels of agreement are clinically unacceptable, the devices
      should not be used interchangeably for initial and follow up measurements.

PMID- 29568702
TI  - Linking influenza epidemic onsets to covariates at different scales using a
      dynamical model.
AB  - Background: Evaluating the factors favoring the onset of influenza epidemics is a
      critical public health issue for surveillance, prevention and control. While past
      outbreaks provide important insights for understanding epidemic onsets, their
      statistical analysis is challenging since the impact of a factor can be viewed at
      different scales. Indeed, the same factor can explain why epidemics are more
      likely to begin (i) during particular weeks of the year (global scale); (ii)
      earlier in particular regions (spatial scale) or years (annual scale) than others
      and (iii) earlier in some years than others within a region (spatiotemporal
      scale). Methods: Here, we present a statistical approach based on dynamical
      modeling of infectious diseases to study epidemic onsets. We propose a method to
      disentangle the role of covariates at different scales and use a permutation
      procedure to assess their significance. Epidemic data gathered from 18 French
      regions over six epidemic years were provided by the Regional Influenza
      Surveillance Group (GROG) sentinel network. Results: Our results failed to
      highlight a significant impact of mobility flows on epidemic onset dates.
      Absolute humidity had a significant impact, but only at the spatial scale. No
      link between demographic covariates and influenza epidemic onset dates could be
      established. Discussion: Dynamical modeling presents an interesting basis to
      analyze spatiotemporal variations in the outcome of epidemic onsets and how they
      are related to various types of covariates. The use of these models is quite
      complex however, due to their mathematical complexity. Furthermore, because they
      attempt to integrate migration processes of the virus, such models have to be
      much more explicit than pure statistical approaches. We discuss the relation of
      this approach to survival analysis, which present significant differences but may
      constitute an interesting alternative for non-methodologists.

PMID- 29568703
TI  - Curious creatures: a multi-taxa investigation of responses to novelty in a zoo
      environment.
AB  - The personality trait of curiosity has been shown to increase welfare in humans.
      If this positive welfare effect is also true for non-humans, animals with high
      levels of curiosity may be able to cope better with stressful situations than
      their conspecifics. Before discoveries can be made regarding the effect of
      curiosity on an animal's ability to cope in their environment, a way of measuring
      curiosity across species in different environments must be created to standardise
      testing. To determine the suitability of novel objects in testing curiosity,
      species from different evolutionary backgrounds with sufficient sample sizes were
      chosen. Barbary sheep (Ammotragus lervia) n = 12, little penguins (Eudyptula
      minor) n = 10, ringtail lemurs (Lemur catta) n = 8, red tailed black cockatoos
      (Calyptorhynchus banksia) n = 7, Indian star tortoises (Geochelone elegans) n = 5
      and red kangaroos (Macropus rufus) n = 5 were presented with a stationary object,
      a moving object and a mirror. Having objects with different characteristics
      increased the likelihood individuals would find at least one motivating.
      Conspecifics were all assessed simultaneously for time to first orientate towards
      object (s), latency to make contact (s), frequency of interactions, and total
      duration of interaction (s). Differences in curiosity were recorded in four of
      the six species; the Barbary sheep and red tailed black cockatoos did not
      interact with the novel objects suggesting either a low level of curiosity or
      that the objects were not motivating for these animals. Variation in curiosity
      was seen between and within species in terms of which objects they interacted
      with and how long they spent with the objects. This was determined by the speed
      in which they interacted, and the duration of interest. By using the measure of
      curiosity towards novel objects with varying characteristics across a range of
      zoo species, we can see evidence of evolutionary, husbandry and individual
      influences on their response. Further work to obtain data on multiple captive
      populations of a single species using a standardised method could uncover factors
      that nurture the development of curiosity. In doing so, it would be possible to
      isolate and modify sub-optimal husbandry practices to improve welfare in the zoo
      environment.

PMID- 29568704
TI  - First endemic freshwater Gammarus from Crete and its evolutionary history-an
      integrative taxonomy approach.
AB  - The Mediterranean islands are known as natural laboratories of evolution with a
      high level of endemic biodiversity. However, most biodiversity assessments have
      focused mainly on terrestrial and marine fauna, leaving the freshwater animals
      aside. Crete is one of the largest islands in the Mediterranean Basin, with a
      long history of isolation from the continental mainland. Gammarid amphipods are
      often dominant in macrozoobenthic communities in European inland waters. They are
      widely used in biomonitoring and exotoxicological studies. Herein, we describe
      Gammarus plaitisi sp. nov., endemic to Cretan streams, based on morphological
      characters and a set of molecular species delimitation methods using
      mitochondrial cytochrome oxidase subunit I and 16S rRNA genes as well as nuclear
      28S rDNA, ITS1 and EF1-alpha genes. The divergence of the new species is strongly
      connected with the geological history of the island supporting its continental
      origin.

PMID- 29568705
TI  - Activation of CD4 and CD8 T cell receptors and regulatory T cells in response to
      human proteins.
AB  - This study assessed in detail the influence of four different human proteins on
      the activation of CD4+ and CD8+ T lymphocytes and on the formation of regulatory
      T cells. Human whole-blood samples were incubated with four different human
      proteins. The effects of these proteins on the downstream immune-system response,
      on the expression of extracellular activation markers on and intracellular
      cytokines in T lymphocytes, and on the number of regulatory T cells (T-reg cells)
      were investigated via flow cytometry. Incubation with beta-actin or
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which are cytoplasmic proteins,
      increased the expression of both extracellular activation markers (CD69 and HLA
      DR) and intracellular cytokines but did not significantly affect the number of T
      reg cells. In contrast, incubation with human albumin or insulin, which are serum
      proteins, reduced both extracellular activation markers and intracellular
      cytokine expression and subsequently increased the number of T-reg cells. These
      findings may help to explain the etiological basis of autoimmune diseases.

PMID- 29568707
TI  - Games between stakeholders and the payment for ecological services: evidence from
      the Wuxijiang River reservoir area in China.
AB  - A gambling or "game" phenomenon can be observed in the complex relationship
      between sources and receptors of ecological compensation among multiple
      stakeholders. This paper investigates the problem of gambling to determine
      payment amounts, and details a method to estimate the ecological compensation
      amount related to water resources in the Wuxijiang River reservoir area in China.
      Public statistics and first-hand data obtained from a field investigation were
      used as data sources. Estimation of the source and receptor amount of ecological
      compensation relevant to the water resource being investigated was achieved using
      the contingent valuation method (CVM). The ecological compensation object and its
      benefit and gambling for the Wuxijiang River water source area are also analyzed
      in this paper. According to the results of a CVM survey, the ecological
      compensation standard for the Wuxijiang River was determined by the CVM, and the
      amount of compensation was estimated. Fifteen blocks downstream of the Wuxijiang
      River and 12 blocks in the water source area were used as samples to administer a
      survey that estimated the willingness to pay (WTP) and the willingness to accept
      (WTA) the ecological compensation of Wuxijiang River for both nonparametric and
      parametric estimation. Finally, the theoretical value of the ecological
      compensation amount was estimated. Without taking other factors into account, the
      WTP of residents in the Wuxi River water source was 297.48 yuan per year, while
      the WTAs were 3864.48 yuan per year. The theoretical standard of ecological
      compensation is 2294.39-2993.81 yuan per year. Under the parameter estimation of
      other factors, the WTP of residents in the Wuxi River water source area was
      528.72 yuan per year, while the WTA was 1514.04 yuan per year. The theoretical
      standard of ecological compensation is 4076.25-5434.99 yuan per year. The main
      factors influencing the WTP ecological compensation in the Wuxi River basin are
      annual income and age. The main factors affecting WTA are gender and attention to
      the environment, age, marital status, local birth, and location in the main
      village.

PMID- 29568706
TI  - Current state of knowledge on Wolbachia infection among Coleoptera: a systematic
      review.
AB  - Background: Despite great progress in studies on Wolbachia infection in insects,
      the knowledge about its relations with beetle species, populations and
      individuals, and the effects of bacteria on these hosts, is still unsatisfactory.
      In this review we summarize the current state of knowledge about Wolbachia
      occurrence and interactions with Coleopteran hosts. Methods: An intensive search
      of the available literature resulted in the selection of 86 publications that
      describe the relevant details about Wolbachia presence among beetles. These
      publications were then examined with respect to the distribution and taxonomy of
      infected hosts and diversity of Wolbachia found in beetles. Sequences of
      Wolbachia genes (16S rDNA, ftsZ) were used for the phylogenetic analyses.
      Results: The collected publications revealed that Wolbachia has been confirmed in
      204 beetle species and that the estimated average prevalence of this bacteria
      across beetle species is 38.3% and varies greatly across families and genera (0
      88% infected members) and is much lower (c. 13%) in geographic studies. The
      majority of the examined and infected beetles were from Europe and East Asia. The
      most intensively studied have been two groups of herbivorous beetles:
      Curculionidae and Chrysomelidae. Coleoptera harbor Wolbachia belonging to three
      supergroups: F found in only three species, and A and B found in similar numbers
      of beetles (including some doubly infected); however the latter two were most
      prevalent in different families. A total of 59% of species with precise data were
      found to be totally infected. Single infections were found in 69% of species and
      others were doubly- or multiply-infected. Wolbachia caused numerous effects on
      its beetle hosts, including selective sweep with host mtDNA (found in 3% of
      species), cytoplasmic incompatibility (detected in c. 6% of beetles) and other
      effects related to reproduction or development (like male-killing, possible
      parthenogenesis or haplodiploidy induction, and egg development). Phylogenetic
      reconstructions for Wolbachia genes rejected cospeciation between these bacteria
      and Coleoptera, with minor exceptions found in some Hydraenidae, Curculionidae
      and Chrysomelidae. In contrast, horizontal transmission of bacteria has been
      suspected or proven in numerous cases (e.g., among beetles sharing habitats
      and/or host plants). Discussion: The present knowledge about Wolbachia infection
      across beetle species and populations is very uneven. Even the basic data about
      infection status in species and frequency of infected species across genera and
      families is very superficial, as only c. 0.15% of all beetle species have been
      tested so far. Future studies on Wolbachia diversity in Coleoptera should still
      be based on the Multi-locus Sequence Typing system, and next-generation
      sequencing technologies will be important for uncovering Wolbachia relations with
      host evolution and ecology, as well as with other, co-occurring endosymbiotic
      bacteria.

PMID- 29568708
TI  - Cd and Zn interactions and toxicity in ectomycorrhizal basidiomycetes in axenic
      culture.
AB  - Background: Metal contamination in soils affects both above- and belowground
      communities, including soil microorganisms. Ectomycorrhizal (ECM) fungi are an
      important component in belowground community and tolerant strains have great
      potential in enhancing plant-based remediation techniques. We assessed cadmium
      and zinc toxicity in five ECM species in liquid media (Hebeloma subsaponaceum; H.
      cylindrosporum; H. crustuliniforme; Scleroderma sp.; Austroboletus occidentalis)
      and investigated the potential of Zn to alleviate Cd toxicity. Due to highly
      divergent results reported in the literature, liquid and solid media were
      compared experimentally for the first time in terms of differential toxicity
      thresholds in Cd and Zn interactions. Methods: A wide range of Cd and Zn
      concentrations were applied to ectomycorrhizal fungi in axenic cultures (in mg L
      1): 0; 1; 3; 9; 27; 81; 243 for the Cd treatments, and 0; 1; 30; 90; 270; 810;
      2,430 for Zn. Combined Zn and Cd treatments were also applied to H. subsaponaceum
      and Scleroderma sp. Dry weight was recorded after 30 days, and in case of solid
      medium treatments, radial growth was also measured. Results and Discussion: All
      species were adversely affected by high levels of Cd and Zn, and A. occidentalis
      was the most sensitive, with considerable biomass decrease at 1 mg L-1 Cd, while
      Scleroderma sp. and H. subsaponaceum were the most tolerant, which are species
      commonly found in highly contaminated sites. Cd was generally 10 times more toxic
      than Zn, which may explain why Zn had little impact in alleviating Cd effects. In
      some cases, Cd and Zn interactions led to a synergistic toxicity, depending on
      the concentrations applied and type of media used. Increased tolerance patterns
      were detected in fungi grown in solid medium and may be the cause of divergent
      toxicity thresholds found in the literature. Furthermore, solid medium allows
      measuring radial growth/mycelial density as endpoints which are informative and
      in this case appeared be related to the high tolerance indices found in H.
      subsaponaceum.

PMID- 29568709
TI  - Gender, age, and concomitant diseases of melanosis coli in China: a multicenter
      study of 6,090 cases.
AB  - Backgrounds and Aims: Melanosis coli (MC) is a noninflammatory, benign, and
      reversible colonic disorder, but its detection rates in China are unclear. We
      therefore aimed to analyze the epidemiological characteristics of MC in China.
      Methods: We assessed the detection rates, associated factors and concomitant
      diseases of MC in the patients who underwent colonoscopy at eight medical centers
      across five regions of China between January 2006 and October 2016. All data were
      procured from the electronic database established at each participating
      institutions. Results: Among the 342,922 included cases, MC was detected in 6,090
      cases (detection rate = 1.78%, 95% confidence interval, 1.73%-1.82%) at a mean
      age of 60 years. The detection rate gradually increased yearly, and along with
      the increasing age regardless of gender, while a rapid increase presented in the
      patients >=60 years of age (0.58% for <=25 years, 1.22% for 25-59 years, and
      3.19% for >=60 years). The detection rate was higher in females than in males;
      however, the rate of per-year increase was higher in males than in females at age
      of >=60 years, which was 1.85-fold of that in females. Among cancer, polyp,
      inflammation, and diverticula, polyp was the most common concomitant disease of
      MC and identified in 41.72% of MC patients. Conclusions: MC detection rates were
      increased annually and elevated in older patients, particularly in male patients.
      Males in the elderly population of >=60 years were most likely to have MC.
      Colonic polyp is the most common concomitant disease of MC.

PMID- 29568710
TI  - Effects of landscape features on population genetic variation of a tropical
      stream fish, Stone lapping minnow, Garra cambodgiensis, in the upper Nan River
      drainage basin, northern Thailand.
AB  - Spatial genetic variation of river-dwelling freshwater fishes is typically
      affected by the historical and contemporary river landscape as well as life
      history traits. Tropical river and stream landscapes have endured extended
      geological change, shaping the existing pattern of genetic diversity, but were
      not directly affected by glaciation. Thus, spatial genetic variation of tropical
      fish populations should look very different from the pattern observed in
      temperate fish populations. These data are becoming important for designing
      appropriate management and conservation plans, as these aquatic systems are
      undergoing intense development and exploitation. This study evaluated the effects
      of landscape features on population genetic diversity of Garra cambodgiensis, a
      stream cyprinid, in eight tributary streams in the upper Nan River drainage basin
      (n = 30-100 individuals/location), Nan Province, Thailand. These populations are
      under intense fishing pressure from local communities. Based on 11 microsatellite
      loci, we detected moderate genetic diversity within eight population samples
      (average number of alleles per locus = 10.99 +/- 3.00; allelic richness = 10.12
      +/- 2.44). Allelic richness within samples and stream order of the sampling
      location were negatively correlated (P < 0.05). We did not detect recent
      bottleneck events in these populations, but we did detect genetic divergence
      among populations (Global FST = 0.022, P < 0.01). The Bayesian clustering
      algorithms (TESS and STRUCTURE) suggested that four to five genetic clusters
      roughly coincide with sub-basins: (1) headwater streams/main stem of the Nan
      River, (2) a middle tributary, (3) a southeastern tributary and (4) a
      southwestern tributary. We observed positive correlation between geographic
      distance and linearized FST (P < 0.05), and the genetic differentiation pattern
      can be moderately explained by the contemporary stream network (STREAMTREE
      analysis, R2 = 0.75). The MEMGENE analysis suggested genetic division between
      northern (genetic clusters 1 and 2) and southern (clusters 3 and 4) sub-basins.
      We observed a high degree of genetic admixture in each location, highlighting the
      importance of natural flooding patterns and possible genetic impacts of
      supplementary stocking. Insights obtained from this research advance our
      knowledge of the complexity of a tropical stream system, and guide current
      conservation and restoration efforts for this species in Thailand.

PMID- 29568711
TI  - Validation and application of the Chinese version of the Perceived Stress
      Questionnaire (C-PSQ) in nursing students.
AB  - Objective: To translate the Perceived Stress Questionnaire (PSQ) into Chinese,
      validate its reliability and validity in nursing students and investigate the
      perceived stress level of nursing students. Method: Forward- and back-translation
      combined with expert assessment and cross-cultural adaptations were used to
      construct the Chinese version of the PSQ (C-PSQ). This research adopted a
      stratified sampling method among 1,519 nursing students in 30 classes of Ningbo
      College of Health Sciences to assess the reliability and validity of the C-PSQ.
      Among them, we used the Recent C-PSQ (only the last month). Results: The C-PSQ
      retained all 30 items of the original scale. Principal component analysis
      extracted five factors that explained 52.136% of the total variance. The S
      CVI/Ave was 0.913. Concurrent validity was 0.525 and 0.567 for anxiety and
      depression respectively. The results of the confirmatory factor analysis were as
      follows: chi2/df = 4.376, RMR = 0.023, GFI = 0.921, AGFI = 0.907, CFI = 0.916,
      RMSEA = 0.048, PNFI = 0.832, PGFI = 0.782, CN = 342 and AIC/CAIC = 0.809. The
      scale's Cronbach's alpha was 0.922, and Cronbach's alpha of each dimension was
      0.899 (worries/tension), 0.821 (joy), 0.688 (overload), 0.703 (conflict), 0.523
      (self-realization). The correlation coefficient between the first and second
      test, the first and third test and the second and third test was 0.725, 0.787 and
      0.731, respectively. Mean values and distribution of overall PSQ index in nursing
      students was 0.399 +/- 0.138. Different demographic factors were significantly
      associated with the perceived stress of nursing students. Conclusion: The C-PSQ
      has an appropriate reliability and validity, which means that the scale can be
      used as a universal tool for psychosomatic studies. The perceived stress of
      nursing students was relatively high. Further studies are needed.

PMID- 29568712
TI  - The association between elevated serum uric acid levels and islet beta-cell
      function indexes in newly diagnosed type 2 diabetes mellitus: a cross-sectional
      study.
AB  - Background: Serum uric acid (UA) has been reported as a risk factor for type 2
      diabetes mellitus (T2DM). However, whether serum UA is associated with insulin
      resistance and insulin secretion, and the effect of gender on it in the case of
      the existed association, both remain undefined. Methods: A cross-sectional study
      was designed and performed, which enrolled a total of 403 newly diagnosed T2DM
      patients (mean age, 50.21 +/- 13.34 years (62.5% males)). Clinical
      characteristics and islet function indexes of all participants were analyzed
      based on gender-specific tertiles of serum UA levels. In addition, multiple
      linear regression analysis was conducted to investigate covariates associated
      with islet function indexes. Results: The mean levels of serum UA were 331.05
      MUmol/L (interquartile range (IQR): 60.6, 400.9 MUmol/L) and 267.9 MUmol/L (IQR:
      204.7, 331.9 MUmol/L) in men and women, respectively. The values of insulin
      secretion indexes involving AUCins30/glu30, AUCins120/glu120 and total insulin
      disposition index (DI120) in females were significantly higher than those in
      males. Apart from the homeostasis model assessment insulin resistance of men,
      serum UA was positively associated with insulin secretion and insulin resistance
      indexes both in men and women. Multivariable linear regression analysis showed
      serum UA exerted an independent impact on insulin secretion in females, but not
      on insulin resistance. In males, islet function was simultaneously affected by
      serum UA age, body mass index (BMI), and serum lipids. Conclusion: Serum UA
      harbored a positive correlation with insulin secretion and insulin resistance
      indexes in newly diagnosed T2DM patients, which was influenced by gender, BMI,
      serum lipids. Hence, serum UA may be considered as a predictor for islet function
      in clinical practice.

PMID- 29568713
TI  - Translating New Science Into the Drug Review Process: The US FDA's Division of
      Applied Regulatory Science.
AB  - In 2011, the US Food and drug Administration (FDA) developed a strategic plan for
      regulatory science that focuses on developing new tools, standards, and
      approaches to assess the safety, efficacy, quality, and performance of FDA
      regulated products. In line with this, the Division of Applied Regulatory Science
      was created to move new science into the Center for Drug Evaluation and Research
      (CDER) review process and close the gap between scientific innovation and drug
      review. The Division, located in the Office of Clinical Pharmacology, is unique
      in that it performs mission-critical applied research and review across the
      translational research spectrum including in vitro and in vivo laboratory
      research, in silico computational modeling and informatics, and integrated
      clinical research covering clinical pharmacology, experimental medicine, and
      postmarket analyses. The Division collaborates with Offices throughout CDER,
      across the FDA, other government agencies, academia, and industry. The Division
      is able to rapidly form interdisciplinary teams of pharmacologists, biologists,
      chemists, computational scientists, and clinicians to respond to challenging
      regulatory questions for specific review issues and for longer-range projects
      requiring the development of predictive models, tools, and biomarkers to speed
      the development and regulatory evaluation of safe and effective drugs. This
      article reviews the Division's recent work and future directions, highlighting
      development and validation of biomarkers; novel humanized animal models;
      translational predictive safety combining in vitro, in silico, and in vivo
      clinical biomarkers; chemical and biomedical informatics tools for safety
      predictions; novel approaches to speed the development of complex generic drugs,
      biosimilars, and antibiotics; and precision medicine.

PMID- 29568714
TI  - Oral Health Practices Among Pakistani Physicians.
AB  - Introduction In most healthcare models, the first interaction of a patient is
      with a general physician. The inspection of the oral cavity is a mandatory
      component of the general physical examination performed by a physician. This
      helps detect any oral pathology and make suitable referrals. Therefore, adequate
      oral health awareness is essential for physicians. Our study aimed at evaluating
      the oral health practices among physicians working in a private teaching setup in
      Islamabad, Pakistan. Methods A cross-sectional study involving 144 physicians
      teaching undergraduate medical students at Shifa College of Medicine and its
      affiliated hospital, Shifa International Hospital, was conducted. Participants
      were interviewed through a self-designed questionnaire. Later, each participant
      demonstrated their teeth brushing technique on a standard model of the oral
      cavity, which was assessed against a checklist conforming to the modified bass
      technique. A video clip showing the aforementioned brushing technique was shown
      at the end of the interview. The collected data was analyzed on IBM's statistical
      package for the social sciences (SPSS) version 21.  Results Toothpaste was the
      top choice (97.2%) of teeth cleaning tool with 69% participants brushing their
      teeth two times a day and 56.9% using toothbrushes with bristles of medium
      texture. The use of mouthwash (32.6%) and dental floss (11.1%) was considerably
      low. Dental caries and teeth discoloration were seen in 46.5% and 43.8%
      physicians, respectively. An alarmingly low number of physicians (31.9%) claimed
      to have read guidelines regarding oral health. This translated into most
      participants (78.5%) visiting a dentist only when needed. Only 4.9% participants
      performed all components of the modified bass technique to clean teeth on the
      oral cavity model, with up to 22.9% unable to perform a single step accurately. 
      Conclusion The oral health knowledge and practices of physicians were found to be
      suboptimal and necessitate the integration of oral health awareness in the
      medical curriculum. A multiprofessional approach with physicians in crucial roles
      is required to address the burden of dental diseases globally.

PMID- 29568715
TI  - Not Your Typical Simulation Workshop: Using LEGOs to Train Medical Students on
      the Practice of Effective Communication.
AB  - As students in the health professions transition from the classroom into the
      clinical environment, they will be expected to effectively communicate with their
      team members and their patients. Effective communication skills are essential to
      their ability to effectively contribute to their clinical team and the patient
      care they deliver. The authors propose an interactive workshop that can support
      students' deliberate practice of communication skills. The authors designed a
      simulation workshop that affords students the opportunity to practice their
      communication and peer-to-peer coaching skills. Using LEGOs, a one-hour workshop
      was conducted with medical students. Students were divided into groups of two.
      Each student took on a different role: teacher or builder. Teachers were tasked
      with instructing builders on how to construct a pre-made LEGO structure, not
      allowing builders to look at the structure. A group debriefing followed to
      evaluate the activity and explore the themes that emerged. Twenty first-year
      medical students and 25 fourth-year medical students participated in this
      activity. Most groups were successful in reproducing the pre-made structure.
      Groups that pre-briefed before building were most successful. Unsuccessful groups
      did not define orientation or direction in mutually understood terms, resulting
      in the creation of an incorrect mirror image of the structure - a common
      phenomenon seen during the teaching of procedures in the clinical learning
      environment. The workshop was well received. Students made requests to have
      similar sessions throughout their training to better support the development of
      effective communication skills. The workshop can easily be applied to other
      specialties to assist with procedural skills instruction or in workshops focusing
      on effective communication.

PMID- 29568716
TI  - Cutaneous, Intranasal Blastomycosis Infection in Two Patients from Southern West
      Virginia: Diagnostic Dilemma.
AB  - Blastomycosis is a dimorphic fungus caused by the species of Blastomyces
      dermatitidisand Blastomyces gilchristii, which are endemic to the Ohio River and
      Mississippi River Valleys. It is commonly found in soil or decomposing wood. It
      is capable of infecting both immunocompromised and immunocompetent patients via
      the respiratory tract by inhaling conidia, where it may remain asymptomatic for a
      prolonged period of time. Extrapulmonary complications can occur in disseminated
      disease due to haematogenous spread from the lungs to other organ systems.
      Haematogenous dissemination from the lungs occurs most commonly to the skin.
      Although rare, primary cutaneous blastomycosis can also occur with direct
      inoculation through the trauma of the skin. Patients presenting with cutaneous
      blastomycosis are often misdiagnosed with malignant neoplasms and may not be
      appropriately managed until further testing and tissue biopsy. Currently, there
      are only four previous case reports of blastomycosis presenting in the intranasal
      region. We report two cases of cutaneous blastomycosis of the nasal passages and
      upper lip with pulmonary manifestations in Southern West Virginia. These patients
      first presented with cutaneous symptoms, which were originally treated for
      melanoma and squamous cell carcinoma and were later diagnosed with systemic
      blastomycosis.

PMID- 29568717
TI  - A Web-based Decision Tool to Estimate Subarachnoid Hemorrhage Risk in Emergency
      Department Patients.
AB  - Subarachnoid hemorrhage (SAH) from a leaking aneurysm is a neurological
      emergency. SAH patients often present with headache-a common chief complaint
      among emergency department patients. If unrecognized, 70% of the patients with re
      bleeds die and one third are left with neurological deficits. Therefore, it is
      critical to distinguish the signs and symptoms of SAH from benign causes of
      headache, perform the appropriate diagnostic tests and treat in a timely manner
      in order to reduce the disability and mortality associated with this condition.
      In patients with suspected SAH, traditional diagnostic strategies in the
      emergency department employ non-contrast computed tomography (CT) of the brain to
      detect blood in the subarachnoid space followed by lumbar puncture if there is a
      high clinical probability of aneurysmal bleed without any evidence of blood on CT
      scan. While the older generation CT scanners were less sensitive to blood
      detection in the subarachnoid space, recent advances in CT imaging have resulted
      in sensitivity approaching 100% for detection of blood in the subarachnoid space
      specifically within six hours of symptom onset. Therefore, the benefit of lumbar
      puncture is controversial when performed within the first six hours of symptom
      onset. Despite this, lumbar puncture is still commonly performed in the emergency
      department, exposing patients to unnecessary procedural risks. The objective of
      this research study is to develop a web-based risk calculator that estimates the
      risk of SAH based on time to emergency department presentation after symptom
      onset, physical findings and imaging characteristics with the goal of reducing
      unnecessary lumbar punctures in the emergency department. In this technical
      report, we describe the prototype calculator, the mathematical basis of the model
      and provide a link to the web-based prototype. In the future, we will refine the
      prototype, make it user-friendly to physicians, staff and patients and study its
      benefits in the emergency department.

PMID- 29568718
TI  - Sleep and Speech Outcomes After Superior Adenoidectomy in Children with Cleft
      Palate.
AB  - Objective To describe the sleep and speech outcomes in patients with cleft palate
      who underwent superior adenoidectomy. Subjectives and methods This is a case
      series with chart review of patients with diagnoses of cleft palate and sleep
      disordered breathing (SDB), obstructive sleep apnea (OSA) or nasal obstruction
      treated with superior adenoidectomy from 1991-2015 at the Children's Hospital of
      Minnesota. Postoperative clinic notes documented the changes in symptoms
      following surgery. All speech outcomes were recorded. Results Fifty patients (23
      females, 27 males) aged 11 months to 17 years were included. Forty-six patients
      (92%) had improvement of sleep symptoms including snoring, nighttime
      restlessness, and witnessed apnea events, following superior adenoidectomy. Forty
      two of the 46 patients (91%) had stable speech postoperatively with either no
      development or no worsening of velopharyngeal insufficiency (VPI). Conclusion
      Superior adenoidectomy is an effective procedure to alleviate symptoms of sleep
      disordered breathing in patients with cleft palate without significantly
      affecting speech.

PMID- 29568719
TI  - Wind-Driven Erosion and Exposure Potential at Mars 2020 Rover Candidate-Landing
      Sites.
AB  - Aeolian processes have likely been the predominant geomorphic agent for most of
      Mars' history and have the potential to produce relatively young exposure ages
      for geologic units. Thus, identifying local evidence for aeolian erosion is
      highly relevant to the selection of landing sites for future missions, such as
      the Mars 2020 Rover mission that aims to explore astrobiologically relevant
      ancient environments. Here we investigate wind-driven activity at eight Mars 2020
      candidate-landing sites to constrain erosion potential at these locations. To
      demonstrate our methods, we found that contemporary dune-derived abrasion rates
      were in agreement with rover-derived exhumation rates at Gale crater and could be
      employed elsewhere. The Holden crater candidate site was interpreted to have low
      contemporary erosion rates, based on the presence of a thick sand coverage of
      static ripples. Active ripples at the Eberswalde and southwest Melas sites may
      account for local erosion and the dearth of small craters. Moderate-flux regional
      dunes near Mawrth Vallis were deemed unrepresentative of the candidate site,
      which is interpreted to currently be experiencing low levels of erosion. The Nili
      Fossae site displayed the most unambiguous evidence for local sand transport and
      erosion, likely yielding relatively young exposure ages. The downselected Jezero
      crater and northeast Syrtis sites had high-flux neighboring dunes and exhibited
      substantial evidence for sediment pathways across their ellipses. Both sites had
      relatively high estimated abrasion rates, which would yield young exposure ages.
      The downselected Columbia Hills site lacked evidence for sand movement, and
      contemporary local erosion rates are estimated to be relatively low.

PMID- 29568720
TI  - Emerging pollutants in the EU: 10 years of NORMAN in support of environmental
      policies and regulations.
AB  - In 2005, the European Commission funded the NORMAN project to promote a permanent
      network of reference laboratories and research centers, including academia,
      industry, standardization bodies, and NGOs. Since then, NORMAN has (i)
      facilitated a more rapid and wide-scope exchange of data on the occurrence and
      effects of contaminants of emerging concern (CECs), (ii) improved data quality
      and comparability via validation and harmonization of common sampling and
      measurement methods (chemical and biological), (iii) provided more transparent
      information and monitoring data on CECs, and (iv) established an independent and
      competent forum for the technical/scientific debate on issues related to emerging
      substances. NORMAN plays a significant role as an independent organization at the
      interface between science and policy, with the advantage of speaking to the
      European Commission and other public institutions with the "bigger voice" of more
      than 70 members from 20 countries. This article provides a summary of the first
      10 years of the NORMAN network. It takes stock of the work done so far and
      outlines NORMAN's vision for a Europe-wide collaboration on CECs and sustainable
      links from research to policy-making. It contains an overview of the state of
      play in prioritizing and monitoring emerging substances with reference to several
      innovative technologies and monitoring approaches. It provides the point of view
      of the NORMAN network on a burning issue-the regulation of CECs-and presents the
      positions of various stakeholders in the field (DG ENV, EEA, ECHA, and national
      agencies) who participated in the NORMAN workshop in October 2016. The main
      messages and conclusions from the round table discussions are briefly presented.

PMID- 29568721
TI  - Monoamine Oxidase A in Antisocial Personality Disorder and Borderline Personality
      Disorder.
AB  - Purpose of Review: Variation in the monoamine oxidase A (MAO-A) gene and MAO-A
      enzyme levels have been linked to antisocial behavior and aggression in clinical
      and non-clinical populations. Here, we provide an overview of the genetic,
      epigenetic, and neuroimaging research that has examined MAO-A structure and
      function in antisocial personality disorder (ASPD) and borderline personality
      disorder (BPD). Recent Findings: The low-activity MAO-A variable nucleotide
      tandem repeat genetic polymorphism has shown a robust association with large
      samples of violent and seriously violent offenders, many of whom had ASPD. A
      recent positron emission tomography (PET) study of ASPD similarly revealed low
      MAO-A density in brain regions thought to contribute to the psychopathology of
      the condition. By contrast, PET has also demonstrated that brain MAO-A levels are
      increased in BPD and that they relate to symptoms of low mood and suicidality.
      Summary: Candidate gene studies have produced the most compelling evidence
      connecting MAO-A genetic variants to both ASPD and BPD. Still, conflicting
      results abound in the literature, making it highly unlikely that ASPD or BPD is
      related to a specific MAO-A genetic variant. Future research should strive to
      examine how MAO-A genotypes interact with broad-spectrum environmental influences
      to produce brain endophenotypes that may ultimately become tractable targets for
      novel treatment strategies.

PMID- 29568722
TI  - Universal behaviour of high-Q Fano resonances in metamaterials: terahertz to near
      infrared regime.
AB  - The observation of Fano resonance phenomena is universal across several branches
      of physics. Photonics is one of the most important areas of physics that mainly
      deals with the control of light propagation and localization through its
      interaction with natural and artificially engineered media. In an era of
      miniaturization, manipulation of light at micro-nanoscales has assumed
      unprecedented significance due to its potential to satisfy the mankind with
      disruptive future technologies. In this work, we present our study on the
      universality of high quality factor Fano resonances in planar metamaterials
      across terahertz and infrared parts of the electromagnetic spectrum. The narrow
      linewidth asymmetric Fano resonant metamaterials have tremendous potential to
      find applications in micro-nanoscale flat lasers, sensors, and ultra-resolution
      spectrometers.

PMID- 29568724
TI  - ASCI: providing a forum for imaging scientists.

PMID- 29568723
TI  - Feature extraction via similarity search: application to atom finding and
      denoising in electron and scanning probe microscopy imaging.
AB  - We develop an algorithm for feature extraction based on structural similarity and
      demonstrate its application for atom and pattern finding in high-resolution
      electron and scanning probe microscopy images. The use of the combined local
      identifiers formed from an image subset and appended Fourier, or other transform,
      allows tuning selectivity to specific patterns based on the nature of the
      recognition task. The proposed algorithm is implemented in Pycroscopy, a
      community-driven scientific data analysis package, and is accessible through an
      interactive Jupyter notebook available on GitHub.

PMID- 29568725
TI  - Management of Septated Malignant Pleural Effusions.
AB  - Purpose of Review: We review recent studies of patients with septated malignant
      pleural effusions, to understand what the clinical implications for patients are
      and what evidence-based methods should be used to manage these effusions. Recent
      Findings: Fibrinolytics improve effusion size assessed radiologically in patients
      with a chest drain inserted for septated malignant pleural effusions but this
      does not translate into an improvement in breathlessness relief or pleurodesis
      success. Fibrinolytics have also been used in patients with septated effusions
      associated with indwelling pleural catheters, but dyspnoea relief has not been
      assessed in this population. Patients with septated effusions or extensive
      adhesions appear to have a worse prognosis. Summary: Patients with septated
      malignant pleural effusions have a poor prognosis and do not gain clinical
      benefit from fibrinolytics via chest drain. The role of fibrinolytics for
      septated effusions associated with indwelling pleural catheters requires further
      study.

PMID- 29568726
TI  - Promoting recovery from severe mental illness: Implications from research on
      metacognition and metacognitive reflection and insight therapy.
AB  - Research indicates that individuals with schizophrenia recover. Recovery, however
      means different things to different individuals and regardless of what kind of
      experiences define recovery, the individual diagnosed with the serious mental
      illness must feel ownership of their recovery. This raises the issue of how
      mental health services should systematically promote recovery. This paper
      explores the practical implications for research on metacognition in
      schizophrenia for this issue. First, we present the integrated model of
      metacognition, which defines metacognition as the spectrum of activities which
      allow individual to have available to themselves an integrated sense of self and
      others as they appraise and respond to the unique challenges they face. Second,
      we present research suggesting that many with schizophrenia experience deficits
      in metacognition and that those deficits compromise individuals' abilities to
      manage their lives and mental health challenges. Third, we discuss a form of
      psychotherapy inspired by this research, Metacognitive Reflection and Insight
      Therapy which assists individuals to recapture the ability to form integrated
      ideas about themselves and others and so direct their own recovery. The need for
      recovery oriented interventions to focus on process and on patient's purposes,
      assess metacognition and consider the intersubjective contexts in which this
      occurres is discussed.

PMID- 29568727
TI  - Complex posttraumatic stress disorder: The need to consolidate a distinct
      clinical syndrome or to reevaluate features of psychiatric disorders following
      interpersonal trauma?
AB  - Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed
      as a distinct clinical entity in the WHO International Classification of
      Diseases, 11th version, due to be published, two decades after its first
      initiation. It is described as an enhanced version of the current definition of
      PTSD, with clinical features of PTSD plus three additional clusters of symptoms
      namely emotional dysregulation, negative self-cognitions and interpersonal
      hardship, thus resembling the clinical features commonly encountered in
      borderline personality disorder (BPD). Complex PTSD is related to complex trauma
      which is defined by its threatening and entrapping context, generally
      interpersonal in nature. In this manuscript, we review the current findings
      related to traumatic events predisposing the above-mentioned disorders as well as
      the biological correlates surrounding them, along with their clinical features.
      Furthermore, we suggest that besides the present distinct clinical diagnoses
      (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that
      follow a continuum of trauma and biological severity on a spectrum of common or
      similar clinical features and should be treated as such. More studies are needed
      to confirm or reject this hypothesis, particularly in clinical terms and how they
      correlate to clinical entities' biological background, endorsing a shift from the
      phenomenologically only classification of psychiatric disorders towards a more
      biologically validated classification.

PMID- 29568728
TI  - Repeatability of two-dimensional chemical shift imaging multivoxel proton
      magnetic resonance spectroscopy for measuring human cerebral choline-containing
      compounds.
AB  - AIM: To investigate the repeatability of proton magnetic resonance spectroscopy
      in the in vivo measurement of human cerebral levels of choline-containing
      compounds (Cho). METHODS: Two consecutive scans were carried out in six healthy
      resting subjects at a magnetic field strength of 1.5 T. On each occasion,
      neurospectroscopy data were collected from 64 voxels using the same 2D chemical
      shift imaging (CSI) sequence. The data were analyzed in the same way, using the
      same software, to obtain the values for each voxel of the ratio of Cho to
      creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation
      (CV), repeatability coefficient (RC), and intraclass correlation coefficient
      (ICC) were used to assess the repeatability. RESULTS: The CV ranged from 2.75% to
      33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as
      judged by significant ICC values, in 26 voxels. Just three voxels showed
      significant differences according to the Wilcoxon related-samples signed-rank
      test. CONCLUSION: It is therefore concluded that when CSI multivoxel proton
      neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5
      T, the reproducibility is highly acceptable.

PMID- 29568729
TI  - Audit of physical health monitoring in children and adolescents receiving
      antipsychotics in neurodevelopmental clinics in Northumberland.
AB  - AIM: To ascertain performance against the standards set by National Institute for
      Clinical Excellence (NICE) guidelines on physical health monitoring of thirty
      children and adolescents prescribed antipsychotics in neurodevelopmental clinics
      in Northumberland and identifying areas for improvement in practice. METHODS: The
      audit involved a review of recorded documentation pertaining to physical health
      monitoring in patient electronic records pertaining to children and adolescents
      attending neurodevelopmental clinics in Northumberland prescribed antipsychotics.
      Clients were also contacted by telephone if relevant documentation could not be
      identified or retrieved to confirm the details. 32 case notes were perused of
      which 2 were excluded as they had refused to have venepuncture which was
      documented in the electronic records. RESULTS: The overall audit results
      demonstrated partial compliance with NICE guidelines on physical health
      monitoring in children and adolescents prescribed antipsychotics. Bi-annual
      recording of height, weight, blood pressure, pulse rate and review of side
      effects was completed in 100% of subjects. However, annual monitoring for blood
      tests including liver function, renal function full blood count as well as
      biannual monitoring of serum prolactin, serum lipid profile was completed only in
      56% of subjects. Comparative baseline characteristics between the two groups
      (compliant and non-compliant with guidelines) found no differences based on any
      socio-demographic or clinical variables. However, the proportion of patients in
      the group compliant to guidelines was higher in the age group of 12-17 years as
      compared to < 12 years (70.58% vs 38.46%), though not statistically significant
      (chi2 = 1.236; P = 0.24). CONCLUSION: Development of tailored and specific
      guidelines for physical health monitoring in children and adolescents prescribed
      antipsychotics taking into consideration clinical effectiveness and safety
      profile is likely to improve adherence rates.

PMID- 29568730
TI  - Factors associated with tobacco, alcohol, and other drug use among youth living
      in West Central Mexico.
AB  - AIM: To determine the prevalence of drug and substance abuse among high school
      students in Jalisco and its association with the severity of health, behavior and
      psychosocial problems in order to provide evidence for possible prevention and
      treatment needs. METHODS: A multi-stage random sample of Jalisco high school
      students was given a paper-and-pencil survey based upon an adapted version of the
      drug use screening inventory (DUSI) (n = 24699; n = 2832). The DUSI showed
      adequate psychometric characteristics in this population. The statistical
      analyses accommodated the complex survey design with attention to unequal
      probability of selection and clustering of participants within schools and
      regions. RESULTS: An estimated 44% of the students had smoked tobacco, one in
      five students was a current smoker, and one in four students used to smoke but
      had not smoked for one year or more. By contrast, 6.8% of the students reported
      having used marijuana, cocaine, or both. Behavioral problems, deviant peer
      affiliation, and troubled families were independently associated with drug use.
      One in two students who used tobacco or alcohol had used these drugs in the past
      year (46% and 54%, respectively), and one in four students who used marijuana or
      cocaine in their lifetime had used those drugs in the past year (28% in both
      cases). CONCLUSION: The rates of cocaine use as well as the proportion of current
      users were higher than expected among high school students and indicate changing
      patterns of drug use in Mexico. These results corroborate that the general trend
      of drug use by youth in Mexico is increasing. Results from this study help us
      better understand the needs of at-risk youth and the need for new treatment and
      prevention strategies.

PMID- 29568731
TI  - Bullying among people with visual impairment: Prevalence, associated factors and
      relationship to self-efficacy and life satisfaction.
AB  - AIM: To examine associated factors of bullying and to determine associations
      between bullying and psychosocial outcomes among individuals with visual
      impairments (VI). METHODS: We conducted an age-stratified cross-sectional survey
      of adults with VI who were recruited from the Norwegian Association of the Blind
      and Partially Sighted. Data were collected through structural telephone
      interviews in the period between February and May, 2017. Linear regression models
      were used to examine factors related to bullying and associations of bullying
      with self-efficacy and life satisfaction. RESULTS: A total of 736 individuals
      were interviewed. The lifetime and 6-mo prevalence of bullying was 41.7% and
      8.2%, respectively. The majority of bullied participants reported VI-specific
      bullying (65.1%). Victimization of bullying was associated with young age, early
      onset-age of VI, and having other impairments. Participants who reported bullying
      had lower levels of self-efficacy [Adjusted relative risk (ARR): 0.40, 95%
      confidence interval (CI): 0.19-0.85] and life satisfaction (ARR: 0.68, 95%CI:
      0.51-0.91). CONCLUSION: Bullying is highly prevalent among individuals with VI.
      Our findings suggest that interventions to reduce bullying may be beneficial for
      improving the well-being and life quality of people with VI.

PMID- 29568732
TI  - Role of Murine Complement Component C5 in Acute in Vivo Infection by Pathogenic
      Leptospira interrogans.
AB  - Leptospirosis is considered one of the most important zoonosis worldwide. The
      activation of the Complement System is important to control dissemination of
      several pathogens in the host. Only a few studies have employed murine models to
      investigate leptospiral infection and our aim in this work was to investigate the
      role of murine C5 during in vivo infection, comparing wild type C57BL/6 (B6
      C5+/+) and congenic C57BL/6 (B6 C5-/-, C5 deficient) mice during the first days
      of infection. All animals from both groups survived for at least 8 days post
      infection with pathogenic Leptospira interrogans serovar Kennewicki strain Fromm
      (LPF). At the third day of infection, we observed greater numbers of LPF in the
      liver of B6 C5-/- mice when compared to B6 C5+/+ mice. Later, on the sixth day of
      infection, the LPF population fell to undetectable levels in the livers of both
      groups of mice. On the third day, the inflammatory score was higher in the liver
      of B6 C5+/+ mice than in B6 C5-/- mice, and returned to normal on the sixth day
      of infection in both groups. No significant histopathological differences were
      observed in the lung, kidney and spleen from both infected B6 C5+/+ than B6 C5-/-
      mice. Likewise, the total number of circulating leukocytes was not affected by
      the absence of C5. The liver levels of IL-10 on the sixth day of infection was
      lower in the absence of C5 when compared to wild type mice. No significant
      differences were observed in the levels of several inflammatory cytokines when B6
      C5+/+ and B6 C5-/- were compared. In conclusion, C5 may contribute to the direct
      killing of LPF in the first days of infection in C57BL/6 mice. On the other hand,
      other effector immune mechanisms probably compensate Complement impairment since
      the mice survival was not affected by the absence of C5 and its activated
      fragments, at least in the early stage of this infection.

PMID- 29568733
TI  - New marine gastropod records for the Hellenic waters.
AB  - Background: The Hellenic Seas are influenced by on-going environmental changes
      and the introduction of alien species, which are expected to have an impact on
      their biodiversity. This study contributes to the knowledge of the Hellenic
      marine gastropod biodiversity, expanding data over the entire Greek territory,
      during the period from October 2008 to March 2017. Results: This work presents 45
      species of gastropods not previously reported from Greece or reported only once,
      belonging to 19 families. From those species, one (Horologica sp.) is, most
      probably, an undescribed species, 17 are new for the Eastern Mediterranean Sea
      and 40 are new for the Hellenic fauna. Main taxonomic characteristics and
      ecological information such as habitat, distribution and origin, are given and
      discussed. Conclusions: By this report, the Hellenic gastropod biodiversity is
      enriched by 40 new records, out of which, 17 are new for the Eastern
      Mediterranean Sea, 4 are Lessepsian migrants previously reported for the
      Mediterranean Sea and 1 is probably a new species.

PMID- 29568734
TI  - FDG-PET/CT for diagnosis of cyst infection in autosomal dominant polycystic
      kidney disease.
AB  - Purpose: Cyst infections are a common complication in autosomal dominant
      polycystic kidney disease (ADPKD). Diagnosing these infections often remains
      challenging. Conventional imaging techniques such as ultrasonography, computed
      tomography (CT), and standard magnetic resonance imaging have several drawbacks
      and disadvantages. The purpose of this pictorial essay was to illustrate and
      discuss the potential value of 18F-fluoro-2-deoxy-d-glucose positron emission
      tomography (FDG-PET)/CT in diagnosing cyst infection in ADPKD. Methods: Exemplary
      (ADPKD) patients who underwent FDG-PET/CT as part of their routine clinical work
      up in our institution are presented to show the potential value and drawbacks of
      this imaging technique in diagnosing cyst infection. In addition, the current
      literature and guidelines on this topic were reviewed. Results: FDG-PET/CT
      appears to be a sensitive method for the detection of cyst infection, but it is
      not infallible. Furthermore, FDG uptake in cysts and cyst-like lesions is not
      specific and clinical and radiological correlations are essential to improve
      specificity and minimize the risk of falsely discarding other diseases, in
      particular malignancy. Conclusion: FDG-PET/CT seems to be a useful imaging
      modality to diagnose cyst infections in ADPKD. However, its exact diagnostic
      value has not been established yet due to the lack of a reliable reference
      standard in previous studies on this topic.

PMID- 29568735
TI  - Outcomes of a National Cohort of Children with Acute Severe Ulcerative Colitis.
AB  - Aim: All Irish children with ulcerative colitis (UC) attend the National Centre
      for Paediatric Gastroenterology at Our Lady's Children's Hospital, Crumlin. The
      aim of this study was to determine the outcomes of children with acute severe
      ulcerative colitis (ASC) and the impact of infliximab on these outcomes following
      its introduction for this indication in 2011. Methods: A retrospective chart
      review of all patients admitted with ASC between January 1, 2009 and December 31,
      2015 was undertaken. Patients were identified from the departmental database
      cross-referenced with the hospital inpatient enquiry system. Inpatients with a
      paediatric ulcerative colitis activity index (PUCAI) of >=65 were included. Data
      collected included baseline demographic and laboratory data, concomitant
      treatments, PUCAI scores on days 3 and 5, second-line treatments, surgery, and
      discharge outcomes. Infliximab dose, frequency, and available therapeutic drug
      monitoring results were recorded, along with clinical response outcomes
      (remission, primary, and secondary loss of response). The cohort was sub-analysed
      to determine if there was any era effect pre- and post-introduction of infliximab
      (2009-2010 and 2011-2015, respectively). Results: Fifty-five patients (M:F =
      1.4:1) were treated for acute severe colitis over the study period (8 in the pre
      infliximab and 47 in the post-infliximab era) and 46/55 (86%) had steroid
      refractory disease. Of these, 7/8 (88%) required colectomy in the pre-infliximab
      era, compared with 15/47 (36%) in the post-infliximab era. The remission rate
      with second-line infliximab was 61% at maximal follow-up. There were no
      identifiable factors that predicted likely success or failure of infliximab,
      including gender, CRP, day-3 and day-5 PUCAI scores. Of the 33 patients treated
      with infliximab, dose increase was required in 23/33 (70%); 21/33 (64%) received
      an accelerated dose schedule, and 9/33 (27%) eventually needed colectomy. Primary
      and secondary loss of response to infliximab was seen in one and nine patients,
      respectively. Conclusion: This is the first population-based study of the
      outcomes of severe UC in Irish children, and suggests a higher burden of steroid
      refractory disease compared with previous international studies. While infliximab
      treatment has led to reduction in colectomy rates, a significant proportion of
      patients lose therapeutic effect.

PMID- 29568736
TI  - A New Approach to Evaluating the Risk-Benefit Equation for Dual-Use and Gain-of
      Function Research of Concern.
AB  - In the twenty-first century, biology faces a problem that has previously vexed
      other disciplines such as physics, namely the prospect that its knowledge domain
      could be used to generate biological agents with altered properties that enhanced
      their weapon potential. Biological weapons bring the additional dimension that
      these could be self-replicating, easy to manufacture and synthesized with
      commonly available expertise. This resulted in increasing concern about the type
      of research done and communicated, despite the fact that such research often has
      direct societal benefits, bringing the dual-use dilemma to biology. The conundrum
      of dual use research of concern was crystallized by the so-called "gain-of
      function" type of experiments in which avian influenza viruses were endowed with
      new properties in the laboratory such as increased virulence and the capacity for
      mammalian transmission. After more than a decade of intensive discussion and
      controversy involving biological experiments with dual-use potential, there is no
      consensus on the issue except for the need to carry out such experiments in the
      safest conditions possible. In this essay, we review the topic with the hindsight
      of several years and suggest that instead of prescribing prohibitions and
      experimental limitations the focus should be on the importance of scientific
      questions at hand. We posit that the importance of a scientific question for
      medical and scientific progress provides a benchmark to determine the acceptable
      level of risk in biological experimentation.

PMID- 29568738
TI  - Noncoding RNAs in Health and Disease.

PMID- 29568737
TI  - Assessment of a Single Decoupling Alchemical Approach for the Calculation of the
      Absolute Binding Free Energies of Protein-Peptide Complexes.
AB  - The computational modeling of peptide inhibitors to target protein-protein
      binding interfaces is growing in interest as these are often too large, too
      shallow, and too feature-less for conventional small molecule compounds. Here, we
      present a rare successful application of an alchemical binding free energy method
      for the calculation of converged absolute binding free energies of a series of
      protein-peptide complexes. Specifically, we report the binding free energies of a
      series of cyclic peptides derived from the LEDGF/p75 protein to the integrase
      receptor of the HIV1 virus. The simulations recapitulate the effect of mutations
      relative to the wild-type binding motif of LEDGF/p75, providing structural,
      energetic and dynamical interpretations of the observed trends. The equilibration
      and convergence of the calculations are carefully analyzed. Convergence is aided
      by the adoption of a single-decoupling alchemical approach with implicit
      solvation, which circumvents the convergence difficulties of conventional double
      decoupling protocols. We hereby present the single-decoupling methodology and
      critically evaluate its advantages and limitations. We also discuss some of the
      challenges and potential pitfalls of binding free energy calculations for complex
      molecular systems which have generally limited their applicability to the
      quantitative study of protein-peptide binding equilibria.

PMID- 29568739
TI  - The Prevalence of Traditional Malpractice during Pregnancy, Child Birth, and
      Postnatal Period among Women of Childbearing Age in Meshenti Town, 2016.
AB  - Background: Cultural practices, beliefs, and taboos are often implicated in
      determining the care received by mothers during pregnancy and child birth which
      is an important determinant of maternal mortality. Objective: To assess
      prevalence of cultural malpractice during pregnancy, child birth, and postnatal
      period among women of childbearing age in Meshenti town, Amhara region, northwest
      Ethiopia, in 2016. Methods: Community based cross-sectional study was conducted
      among women of reproductive age group interviewed during the study period from
      May 10 to June 17, 2016. Total sample size was 318 women of reproductive age
      group. Systematic sampling technique was conducted. Result: Overall, 50.9% of the
      respondents had cultural malpractices during their pregnancy. Out of 318 women,
      62 (19.5%) practiced nutrition taboo, 78 (24.5%) practiced abdominal massage, 87
      (29.7%) delivered their babies at home, 96 (32.8%) avoided colostrums, 132
      (45.2%) washed their baby before 24 hr after delivery, and 6 (6.9%) cut the cord
      by unclean blade. Conclusion and Recommendation: The findings of this study show
      that different traditional malpractice during perinatal period is still
      persisting in spite of modern developments in the world. Health education and
      promoting formal female education are important to decrease or avoid these
      cultural malpractices.

PMID- 29568740
TI  - Feasibility of Computational Fluid Dynamics for Evaluating the Intraventricular
      Hemodynamics in Single Right Ventricle Based on Echocardiographic Images.
AB  - This study introduced a combined computational fluid dynamics (CFD) and
      echocardiography methodology to simulate blood flow in the single right ventricle
      (SRV) and normal ventricles to study the intraventricular flow. Derived from
      echocardiographic image loops, CFD-based three-dimensional (3D) flow models of
      normal subject's left ventricle (LV) and right ventricle (RV) and SRV with and
      without heart failure at three characteristic diastolic statuses were
      reconstructed. The CFD derived morphological and functional measurements in
      normal ventricles and the SRV were validated with echocardiography. The vortex in
      the normal ventricles and the SRV were studied. The morphological and functional
      measurements derived from CFD modeling and echocardiography were comparable, and
      both methods demonstrated the larger volume and higher spherical index in the
      SRV, in particular the SRV with heart failure. All the vortices in the SRV were
      smaller than those in the normal control subject's LV and RV, notably with heart
      failure. Unlike normal LV and RV, no vortex ring was observed in the SRV.
      Echocardiography-based CFD demonstrated the feasibility of quantifying
      ventricular morphology and function; in addition, CFD can detect the abnormal
      flow pattern (smaller or obliterated vortices) in the SRV when compared with
      normal ventricles.

PMID- 29568741
TI  - Alteration of Mevalonate Pathway in Rat Splenic Lymphocytes: Possible Role in
      Cytokines Secretion Regulated by L-Theanine.
AB  - L-Theanine is a nonprotein amino acid in tea, and its immunomodulatory function
      has been confirmed. This study aimed to investigate the effect of L-theanine
      addition on cytokines secretion in rat splenic lymphocytes and explore its
      potential immunomodulatory effects on the mevalonate biosynthetic pathway. Our
      results showed that L-theanine treatment did not influence the proliferation and
      division indexes of the splenic lymphocytes subsets. Interestingly, L-theanine
      treatment had regulated the contents of IFN-gamma, IL-2, IL-4, IL-10, IL-12, and
      TNF-alpha  (P < 0.001) except IL-6 and upregulated the mRNA and protein
      expression of Ras-related protein Rap-1A (Rap1A), 3-hydroxy-3-methylglutaryl-CoA
      reductase (HMGCR), and farnesyl diphosphate synthase (FDPs) (P < 0.001).
      Additionally, there was a positive correlation between Rap1A and HMGCR proteins
      expression and IFN-gamma, IL-4, and IL-6 levels. In conclusion, L-theanine
      regulated the secretion of cytokines probably by activating expression of Rap1A
      and HMGCR proteins involved in the mevalonate biosynthetic pathway in rat splenic
      lymphocytes. Therefore, L-theanine might be a promising potential drug candidate
      as immunopotentiator.

PMID- 29568742
TI  - Therapeutic Effect of Long-Term Epidural Block in Rats with Pregnancy Induced
      Hypertension.
AB  - Background: Pregnancy induced hypertension (PIH) causes a variety of systemic
      disorders that negatively affect the maternal placenta and fetal growth. Epidural
      sympathetic block elicits symptoms of decreased blood pressure. This study was
      designed to determine the therapeutic effect of long-term epidural block in rats
      with PIH. Methods: Forty healthy pregnant Sprague Dawley rats were randomized
      into four groups with each group consisting of 10 rats. On gestation day (GD) 14,
      rats in control group underwent a sham procedure; rats in RUPP group were
      operated on to obtain reduced uterine perfusion pressure (RUPP); rats in RUPP
      plus normal saline (NS) group were also subjected to the RUPP procedure and
      underwent epidural block with 25 MUl normal saline twice daily until delivery;
      rats in RUPP plus epidural block (EB) group were treated as those in RUPP plus NS
      group except that an epidural block with 25 MUl of 0.125% bupivacaine was
      administered two times per day until delivery. On GD 20, blood pressure was
      measured in all groups before delivery, and blood samples were collected in order
      to quantify the serum concentrations of vascular endothelial growth factor (VEGF)
      and soluble fms-like tyrosine kinase 1 (sFlt-1). Results: The mean arterial
      pressure (MAP) of rats in RUPP group (147.6 +/- 6.0 mmHg) was markedly increased
      when compared with control group (80.8 +/- 4.6 mmHg) (p < 0.05). The MAP of rats
      in RUPP plus EB group (114.4 +/- 7.2 mmHg) was clearly decreased in contrast with
      RUPP group but was still higher than in control group (p < 0.05). The variation
      of fetal weight in all groups followed a similar trend to that of MAP. However,
      there were no significant differences between control group and RUPP plus EB
      group with respect to placental weight (p = 0.186). Variation in MAP was
      positively correlated with the expression of sFlt-1 in each group but was
      negatively correlated with VEGF. Conclusion: This study demonstrates that long
      term epidural block decreases blood pressure in PIH rats and improves the serum
      concentrations of VEGF and sFlt-1. Taken together, long-term epidural block may
      have a potential role in PIH treatment.

PMID- 29568743
TI  - The Effects of Structured Physical Activity Program on Social Interaction and
      Communication for Children with Autism.
AB  - The purpose of this study was to investigate the effects of structured physical
      activity program on social interaction and communication of children with autism
      spectrum disorder (ASD). Fifty children with ASD from a special school were
      randomly divided into experimental and control groups. 25 children with ASD were
      placed in the experimental group, and the other 25 children as the control group
      participated in regular physical activity. A total of forty-one participants
      completed the study. A 12-week structured physical activity program was
      implemented with a total of 24 exercise sessions targeting social interaction and
      communication of children with ASD, and a quasi-experimental design was used for
      this study. Data were collected using quantitative and qualitative instruments.
      SSIS and ABLLS-R results showed that an overall improvement in social skills and
      social interaction for the experimental group across interim and posttests, F =
      8.425, p = 0.001 (p < 0.005), and significant improvements appeared in
      communication, cooperation, social interaction, and self-control subdomains (p <
      0.005). Conversely, no statistically significant differences were found in the
      control group (p > 0.005). The study concluded that the special structured
      physical activity program positively influenced social interaction and
      communication skills of children with ASD, especially in social skills,
      communication, prompt response, and frequency of expression.

PMID- 29568744
TI  - Fermentation Conditions and Media Optimization for Isocitric Acid Production from
      Ethanol by Yarrowia lipolytica.
AB  - Isocitric acid exists in the form of four stereoisomers, of which only the threo
      Ds-form (ICA) is a natural active compound, an intermediate of Krebs cycle, and
      suitable for nutritional and pharmaceutical use. In this paper, we propose a
      method for ICA production from ethanol by yeast Yarrowia lipolytica. The effects
      of temperature, pH of the medium, and aeration on the growth of the producer Y.
      lipolytica VKM Y-2373 and synthesis of ICA were studied. An optimal fermentation
      regime, which ensures a good growth of the producer and directed synthesis of the
      target product, was determined. The producer is advised to carry out cultivation
      at 29 degrees C and various pH of the medium and the oxygen concentration (pH 5
      and pO2 20-25% (of saturation) during the growth period and pH 6 and pO2 50-55%
      (of saturation) during the acid formation) on a nutrient medium containing an
      increased content of zinc (0.6 mg/L), iron (1.2 mg/L), and 30 mM itaconic acid
      (inhibitor of isocitrate lyase-the key enzyme of ICA metabolism) should also be
      introduced into the nutrition medium. Such fermentation production mode provides
      90.5 g/L ICA with process selectivity of 80%, mass yield (YICA) of 0.77 g/g, and
      energy yield (etaICA) of 0.278 g/g.

PMID- 29568745
TI  - Whole Peptidoglycan Extracts from the Lactobacillus paracasei subsp. paracasei M5
      Strain Exert Anticancer Activity In Vitro.
AB  - The Lactobacillus paracasei subsp. paracasei M5 strain exerted potential
      anticancer activity through the cell wall. In this study, whole peptidoglycan
      (WPG) was extracted from the Lactobacillus paracasei subsp. paracasei M5 strain
      and was evaluated for anticancer effects as well as its properties. SDS-PAGE
      analysis confirmed the presence of WPG with dominant bands of approximately 14.4
      kDa. Further analysis revealed that the amino acids present in the WPG consisted
      of alanine, glycine, glutamic acid, and lysine in a molar ratio of approximately
      8 : 5 : 3 : 3.5. In addition, the cell viability of HT-29 cells with WPG addition
      was investigated with methyl thiazolyl tetrazolium (MTT) and trypan blue
      exclusion (TBE) assays, and cell apoptosis was analyzed with a transmission
      electron microscope, flow cytometry, and semiquantitative RT-PCR. These results
      showed that WPG exerted cytotoxic effects on colon cancer HT-29 cells in a dose
      dependent manner and upregulated proapoptotic genes, while downregulating
      antiapoptotic genes. The gene expression study definitively revealed that WPG
      induced a mitochondria-mediated apoptotic pathway.

PMID- 29568746
TI  - Metagenomics Biomarkers Selected for Prediction of Three Different Diseases in
      Chinese Population.
AB  - The dysbiosis of human microbiome has been proven to be associated with the
      development of many human diseases. Metagenome sequencing emerges as a powerful
      tool to investigate the effects of microbiome on diseases. Identification of
      human gut microbiome markers associated with abnormal phenotypes may facilitate
      feature selection for multiclass classification. Compared with binary
      classifiers, multiclass classification models deploy more complex discriminative
      patterns. Here, we developed a pipeline to address the challenging
      characterization of multilabel samples. In this study, a total of 300 biomarkers
      were selected from the microbiome of 806 Chinese individuals (383 controls, 170
      with type 2 diabetes, 130 with rheumatoid arthritis, and 123 with liver
      cirrhosis), and then logistic regression prediction algorithm was applied to
      those markers as the model intrinsic features. The estimated model produced an F1
      score of 0.9142, which was better than other popular classification methods, and
      an average receiver operating characteristic (ROC) of 0.9475 showed a significant
      correlation between these selected biomarkers from microbiome and corresponding
      phenotypes. The results from this study indicate that machine learning is a vital
      tool in data mining from microbiome in order to identify disease-related
      biomarkers, which may contribute to the application of microbiome-based precision
      medicine in the future.

PMID- 29568747
TI  - Targeted Next-Generation Sequencing of a Deafness Gene Panel (MiamiOtoGenes)
      Analysis in Families Unsuitable for Linkage Analysis.
AB  - Hearing loss (HL) is a common sensory disorder in humans with high genetic
      heterogeneity. To date, over 145 loci have been identified to cause nonsyndromic
      deafness. Furthermore, there are countless families unsuitable for the
      conventional linkage analysis. In the present study, we used a custom capture
      panel (MiamiOtoGenes) to target sequence 180 deafness-associated genes in 5 GJB2
      negative deaf probands with autosomal recessive nonsyndromic HL from Iran. In
      these 5 families, we detected one reported and six novel mutations in 5 different
      deafness autosomal recessive (DFNB) genes (TRIOBP, LHFPL5, CDH23, PCDH15, and
      MYO7A). The custom capture panel in our study provided an efficient and
      comprehensive diagnosis for known deafness genes in small families.

PMID- 29568748
TI  - Long-Term Clinical Efficacy and Perioperative Safety of Endoscopic Submucosal
      Dissection versus Endoscopic Mucosal Resection for Early Gastric Cancer: An
      Updated Meta-Analysis.
AB  - Background: To systematically evaluate the safety and efficacy of endoscopic
      submucosal dissection (ESD) versus endoscopic mucosal resection (EMR) for early
      gastric cancer (EGC). Methods: We searched the databases of PubMed, Web of
      Science, EMBASE, and the Cochrane Library from January 2000 to April 2017 and
      included studies that compared the outcomes of ESD with EMR for EGC. These
      eligible studies that met the inclusion criteria were screened out and were
      assessed by two independent investigators. Result: In total, 18 retrospective
      cohort studies were eligible for analysis. Our results indicated that ESD is more
      beneficial than EMR in increasing the complete resection rate and en bloc
      resection rate and decreasing the local recurrence rate. However, ESD prolonged
      operative time and increased incidence of gastric perforation than EMR. No
      differences were found in postoperative bleeding rate between the two approaches.
      Conclusion: Compared with EMR, ESD offers higher complete resection rate, higher
      en bloc resection rate, and lower local recurrence rate but has prolonged
      operative time and increased incidence of gastric perfusion. There is no
      statistical difference in the rate of postoperative bleeding between the two
      groups. However, the above conclusion needs further verification by well
      designed, randomized trials with larger samples and long follow-up periods.

PMID- 29568749
TI  - Postactivation Potentiation Following Acute Bouts of Plyometric versus Heavy
      Resistance Exercise in Collegiate Soccer Players.
AB  - Postactivation potentiation is referred to as an acute and temporary enhancement
      of muscle performance resulting from previous muscle contraction. The purpose of
      this study was to compare the acute effect of plyometric exercise (PLY) and heavy
      resistance exercise (RES) on the blood lactate level (BLa) and physical
      performance. Fourteen male collegiate soccer players were randomized to perform
      either RES or PLY first and then crossed over to perform the opposite
      intervention. PLY consisted of 40 jumps, whereas RES comprised ten single
      repetitions at 90% of one repetition maximum. BLa and physical performance
      (countermovement jump height and 20-m sprint) were measured before and at 1 and
      10 min following the exercise. No significant difference was observed in the BLa
      for both exercises (PLY and RES). Relative to baseline, countermovement jump
      (CMJ) height was significantly better for the PLY group after 1 min (P = 0.004)
      and after 10 min (P = 0.001) compared to that of the RES group. The 20-m sprint
      time was significantly better for PLY at 10 min (P = 0.003) compared to that of
      RES. The present study concluded that, compared to RES, PLY causes greater
      potentiation, which leads to improved physical performance. This trial is
      registered with NCT03150277.

PMID- 29568750
TI  - The Effect of Dexmedetomidine on Cognitive Function and Protein Expression of
      Abeta, p-Tau, and PSD95 after Extracorporeal Circulation Operation in Aged Rats.
AB  - Postoperative cognitive dysfunction (POCD) is a kind of serious neurologic
      complications and dexmedetomidine has a certain effect on POCD. However,
      functional mechanism of dexmedetomidine on POCD still remains unclear, so the
      research mainly studied the effect of dexmedetomidine on cognitive function and
      protein expression in hippocampus and prefrontal cortex cerebrospinal fluid after
      extracorporeal circulation operation in aged rats. We Found that, compared with
      POCD group, the cognitive function was improved in POCD + Dex group. We speculate
      that dexmedetomidine could improve the cognitive function after extracorporeal
      circulation operation in aged rats and Abeta, p-Tau, and PSD95 protein might have
      contributed to this favorable outcome.

PMID- 29568752
TI  - Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells
      by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible
      Factor 1alpha.
AB  - Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia
      induced epithelial-mesenchymal transition (EMT), driven by hypoxia-inducible
      factor 1alpha (HIF-1alpha), is involved in cancer progression and metastasis. The
      present study was designed to explore the role of propofol in hypoxia-induced
      resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8
      and 5-ethynyl-2'-deoxyuridine incorporation assay to measure cell viability and
      cell proliferation, respectively, in prostate cancer cell lines. Then, we
      detected HIF-1alpha, E-cadherin, and vimentin expression using western blotting.
      Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer
      cell lines. Propofol not only decreased hypoxia-induced HIF-1alpha expression,
      but also reversed hypoxia-induced EMT by suppressing HIF-1alpha. Furthermore,
      small interfering RNA-mediated silencing of HIF-1alpha reversed the hypoxia
      induced docetaxel resistance, although there was little change in docetaxel
      sensitivity between the hypoxia group and propofol group. The induction of
      hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA
      knockdown conditions, the effects of propofol were obviated. These data support a
      role for propofol in regulating EMT in prostate cancer cells. Taken together, our
      findings demonstrate that propofol plays an important role in hypoxia-induced
      docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential
      drug for overcoming drug resistance in prostate cancer cells via HIF-1alpha
      suppression.

PMID- 29568753
TI  - Western Blot-Based Logistic Regression Model for the Identification of Recent HIV
      1 Infection: A Promising HIV-1 Surveillance Approach for Resource-Limited
      Regions.
AB  - Objectives: Identifying recent infections is necessary to monitor HIV/AIDS
      epidemic; however, it needs to be further developed. Methods and Results:
      Participants were defined as having recent infection or older infection according
      to the estimated duration of HIV-1 infection and further assigned into training
      set and validation set according to their entering time points. Western blot (WB)
      confirmatory test and BED-CEIA were performed. The performance of the two methods
      on recent HIV-1 diagnosis was evaluated and compared. 81 subjects were enrolled
      in the training set and 72 in the validation set. Relative grey ratios of p24,
      p39, p31, p66, gp41, and gp160 were significantly higher in older infected
      patients of the training set. The present status of p55 was more frequently
      missing in recently infected patients in both sets. The logistic stepwise
      regression analysis of WB method shows sensitivity, specificity, and accuracy of
      93.02%, 92.11%, and 92.59%. For BED-CEIA, they were 76.74%, 86.84%, and 81.48%.
      In the validation set, overall agreement rate, sensitivity, and specificity were
      88.46%, 84.78%, and 86.11% in the WB-based method and 50.00%, 84.78%, and 72.22%
      in the BED-CEIA method. Conclusions: WB-based method is a promising approach to
      predict recent HIV-1 infection, especially in resource-limited regions.

PMID- 29568751
TI  - Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical
      Trials and Molecular Mechanism of Action.
AB  - Polyphenols have been reported to have wide spectrum of biological activities
      including major impact on initiation, promotion, and progression of cancer by
      modulating different signalling pathways. Colorectal cancer is the second most
      major cause of mortality and morbidity among females and the third among males.
      The objective of this review is to describe the activity of a variety of
      polyphenols in colorectal cancer in clinical trials, preclinical studies, and
      primary research. The molecular mechanisms of major polyphenols related to their
      beneficial effects on colorectal cancer are also addressed. Synthetic
      modifications and other future directions towards exploiting of natural
      polyphenols against colorectal cancer are discussed in the last section.

PMID- 29568754
TI  - Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant
      Extracts with Potential Antidepressant Actions.
AB  - Monoamine oxidase (MAO) catalyzes the oxidative deamination of amines and
      neurotransmitters and is involved in mood disorders, depression, oxidative
      stress, and adverse pharmacological reactions. This work studies the inhibition
      of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii,
      which are reported to improve and affect mood and mental conditions.
      Subsequently, the antioxidant activity associated with the inhibition of MAO is
      determined in plant extracts for the first time. H. perforatum inhibited human
      MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6
      MUg/mL). Plant extracts were analyzed by HPLC-DAD-MS and contained
      pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids.
      Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this
      isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A
      inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 MUg/L),
      being a thousand times more potent than H. perforatum extracts owing to its
      content of beta-carboline alkaloids (harmaline and harmine). L. meyenii root
      (maca) extracts did not inhibit MAO-A. These plants may exert protective actions
      related to antioxidant effects. Results in this work show that P. harmala and H.
      perforatum extracts exhibit antioxidant activity associated with the inhibition
      of MAO (i.e., lower production of H2O2).

PMID- 29568756
TI  - The Repair of Furcal Perforations in Different Diameters with Biodentine, MTA,
      and IRM Repair Materials: A Laboratory Study Using an E. Faecalis Leakage Model.
AB  - The aim of this study is to evaluate the microleakage of repair materials MTA,
      IRM, and Biodentine applied on furcal perforations with different diameters. One
      hundred and forty extracted human teeth were used in this study. The teeth were
      divided into 2 main groups (60 teeth in each) which were then divided into 3
      subgroups (n = 20). The remaining 20 teeth were divided into 2 groups (10 in
      each) to serve as controls. The furcal areas of the teeth were perforated with #2
      cylindrical burs in Group 1 whereas perforations were made using #4 cylindrical
      burs in Group 2. Each subgroup of both Groups 1 and 2 received ProRoot MTA
      (ProRoot, USA), Biodentine (Septodont), or IRM (Dentsply, USA) to repair the
      perforations. An experimental set-up was established to contaminate repaired
      perforations with E. Faecalis (ATCC29212). The turbidity of bacteria was observed
      on the 7th, 15th, 30th, and 45th days. The data was analysed by chi-square test
      (p > 0.05). The number of bacteria in the group perforated by bur #2 and closed
      by MTA was found to be lower than the other groups on the 7th day (p < 0.05).
      There was no statistical difference in the bacterial counts of other groups on
      the 15th, 30th, and 45th days (p > 0.05). ProRoot MTA was found to be more
      successful in the prevention of bacterial leakage compared to IRM and Biodentine
      in smaller perforations during the 1st week.

PMID- 29568755
TI  - Neuroaging through the Lens of the Resting State Networks.
AB  - Resting state functional magnetic resonance imaging (rs-fMRI) allows studying
      spontaneous brain activity in absence of task, recording changes of Blood
      Oxygenation Level Dependent (BOLD) signal. rs-fMRI enables identification of
      brain networks also called Resting State Networks (RSNs) including the most
      studied Default Mode Network (DMN). The simplicity and speed of execution make rs
      fMRI applicable in a variety of normal and pathological conditions. Since it does
      not require any task, rs-fMRI is particularly useful for protocols on patients,
      children, and elders, increasing participant's compliance and reducing
      intersubjective variability due to the task performance. rs-fMRI has shown high
      sensitivity in identification of RSNs modifications in several diseases also in
      absence of structural modifications. In this narrative review, we provide the
      state of the art of rs-fMRI studies about physiological and pathological aging
      processes. First, we introduce the background of resting state; then we review
      clinical findings provided by rs-fMRI in physiological aging, Mild Cognitive
      Impairment (MCI), Alzheimer Dementia (AD), and Late Life Depression (LLD).
      Finally, we suggest future directions in this field of research and its potential
      clinical applications.

PMID- 29568757
TI  - Remarks on Perfection in Plastic Surgery of the Face.
AB  - An expectation of perfect and close to ideal outcomes is attributed not only to
      aesthetic, but also to reconstructive surgery. Contrary to quite common belief
      and despite great potential, the real chances for achieving attractive appearance
      are limited to relatively simple cases with moderately abnormal morphology,
      sufficient homogenous material, and hardly conspicuous scars potential.
      Therefore, the expectations for fully satisfactory outcomes should be limited to
      jaw surgery, cosmetic rhinoplasty, otoplasty, and some rejuvenation procedures,
      provided the best and uneventful surgery is secured. On the basis of over 40
      years of clinical practice (KK) and survey of about 30,000 photos presenting both
      early and long term outcomes, the authors present their own subjective opinion on
      the value and potential of plastic surgery with regard to aesthetic evaluation.
      The paper is illustrated by numerous examples of plastic and esthetic procedures.

PMID- 29568758
TI  - Surgical Technique and Clinical Analysis of Twelve Cases of Isolated Laparoscopic
      Resection of the Hepatic Caudate Lobe.
AB  - Objective: To describe the surgical procedures of laparoscopic caudate lobectomy
      and analyze its clinical efficiency for treating cancer. Methods: Twelve
      consecutive patients of hepatocellular carcinoma, hepatic hemangioma, and focal
      nodular hyperplasia who received laparoscopic caudate lobectomy in Qilu Hospital
      of Shandong University from January 2013 to January 2017 were included in this
      study. The clinical data, intraoperative parameters, and postoperative outcomes
      were assessed. Results: All 12 patients received totally laparoscopic technique.
      The operative time was 140.8 +/- 95.34 minutes. The average estimated blood loss
      was 97.92 +/- 90.54 ml, and no blood transfusions were required. The mean
      duration of hospital stay was 9.17 +/- 2.88 days. There was no perioperative
      complication or patient mortality in this series. Conclusions: Laparoscopic
      caudate lobectomy is safe and feasible in the selected patients.

PMID- 29568759
TI  - Isolation and Molecular Characterization of a Model Antagonistic Pseudomonas
      aeruginosa Divulging In Vitro Plant Growth Promoting Characteristics.
AB  - The use of microbial technologies in agriculture is currently expanding quite
      rapidly with the identification of new bacterial strains, which are more
      effective in promoting plant growth. In the present study 18 strains of
      Pseudomonas were isolated from soil sample of Balochistan coastline. Among
      isolated Pseudomonas strains four designated as SP19, SP22, PS24, and SP25
      exhibited biocontrol activities against phytopathogenic fungi, that is, Rhizopus
      microsporus, Fusarium oxysporum, Aspergillus niger, Alternaria alternata, and
      Penicillium digitatum; PS24 identified as Pseudomonas aeruginosa by 16srRNA gene
      bank accession number EU081518 was selected on the basis of its antifungal
      activity to explore its potential as plant growth promotion. PS24 showed multiple
      plant growth promoting attributes such as phosphate solubilization activity,
      indole acetic acid (IAA), siderophore, and HCN production. In order to determine
      the basis for antifungal properties, antibiotics were extracted from King B broth
      of PS24 and analyzed by TLC. Pyrrolnitrin antibiotic was detected in the culture
      of strain PS24. PS24 exhibited antifungal activities found to be positive for
      hydrogen cyanide synthase Hcn BC gene. Sequencing of gene of Hcn BC gene of
      strain PS24 revealed 99% homology with the Pseudomonas aeruginosa strain PA01.
      The sequence of PS24 had been submitted in gene bank accession number KR605499.
      Ps. aeruginosa PS24 with its multifunctional biocontrol possessions can be used
      to bioprotect the crop plants from phytopathogens.

PMID- 29568760
TI  - Citrus limon from Tunisia: Phytochemical and Physicochemical Properties and
      Biological Activities.
AB  - Natural plant extracts contain a variety of phenolic compounds which are assigned
      various biological activities. Our work aims to make a quantitative and
      qualitative characterization of the Zest (ZL) and the Flesh (FL) of lemon (Citrus
      limon), to valorize the pharmacological uses of lemon, by evaluating in vitro
      activities (DPPH, free radical scavenging and reducing power). The antibacterial,
      antifungal, and antiproliferative activities were sought in the ability of Citrus
      limon extracts to protect DNA and protein. We found that the ZL contains high
      amounts of phenolics responsible for the important antioxidant properties of the
      extract. However, the FL is richer in flavonoids than the ZL. The FL extract was
      also found to be more effective than the ZL in protecting plasmid DNA against the
      strand breakage induced by hydroxyl radicals. We also concluded that the FL
      extract exhibited potent antibacterial activity unlike ZL. Analysis by LC/MS-MS
      identified 6 compounds (Caffeoyl N-Tryptophan, Hydroxycinnamoyl-Oglucoside acid,
      Vicenin 2, Eriocitrin, Kaempferol-3-O- rutinoside, and Quercetin-3-rutinoside).
      These preliminary results showed that Citrus limon has antibacterial and
      antioxidant activity in vitro. It would be interesting to conduct further studies
      to evaluate the in vivo potential in an animal model.

PMID- 29568761
TI  - Glycyrrhizin Suppresses the Growth of Human NSCLC Cell Line HCC827 by
      Downregulating HMGB1 Level.
AB  - Lung cancer has very high mortality and glycyrrhizin was found to significantly
      inhibit the growth of lung cancer cells in vitro and tissues in mice. However,
      the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is
      still unclear. In this study, we first found that glycyrrhizin inhibited the
      growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration
      and invasion of lung cancer cells, which was suppressed by glycyrrhizin.
      Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which
      is the upstream regulator of HMGB1. Therefore, this study revealed a potential
      mechanism by which glycyrrhizin can inhibit the progression of lung cancer.

PMID- 29568762
TI  - Compromised Dynamic Cerebral Autoregulation in Patients with Epilepsy.
AB  - Objective: The aim of this study is to analyze dynamic cerebral autoregulation
      (dCA) in patients with epilepsy. Methods: One hundred patients with epilepsy and
      100 age- and sex-matched healthy controls were recruited. Noninvasive continuous
      cerebral blood flow velocity of the bilateral middle artery and arterial blood
      pressure were recorded. Transfer function analyses were used to analyze the
      autoregulatory parameters (phase difference and gain). Results: The overall phase
      difference of patients with epilepsy was significantly lower than that of the
      healthy control group (p = 0.046). Furthermore, patients with interictal slow
      wave had significant lower phase difference than the slow-wave-free patients (p =
      0.012). There was no difference in overall phase between focal discharges and
      multifocal discharges in patients with epilepsy. Simultaneously, there was no
      difference in mean phase between the affected and unaffected hemispheres in
      patients with unilateral discharges. In particular, interictal slow wave was an
      independent factor that influenced phase difference in patients with epilepsy (p
      = 0.016). Conclusions: Our study documented that dCA is impaired in patients with
      epilepsy, especially in those with interictal slow wave. The impairment of dCA
      occurs irrespective of the discharge location and type. Interictal slow wave is
      an independent factor to predict impaired dCA in patients with epilepsy. Clinical
      Trial Identifier: This trial is registered with NCT02775682.

PMID- 29568763
TI  - Anterior Capsule of the Lens: Comparison of Morphological Properties and
      Apoptosis Induction following FLACS and Standard Phacoemulsification Surgery.
AB  - Purpose: Comparative evaluation of morphological features of anterior capsules
      and apoptosis induction in epithelial cells after femtosecond laser-assisted
      cataract surgery (FLACS) and standard phacoemulsification surgery. Methods: Group
      1: 30 FLACS anterior capsulotomies and Group 2: 30 manual anterior continuous
      curvilinear capsulorhexes. All patients were operated on by the same experienced
      surgeon. Morphological features of the anterior capsules and apoptosis induction
      in epithelial cells were evaluated. Results: All patients revealed a significant
      mean best-corrected visual acuity (BCVA) improvement 3 months after surgery, and
      no major intraoperative nor postoperative complications occurred. The capsular
      epithelium appeared to be preserved in both groups. Scanning electron microscopy
      analysis revealed irregular saw-tooth shaped edges in capsules from Group 1
      whereas capsules from Group 2 showed regular and smooth edges. A statistically
      significant higher expression of the downstream apoptotic effector cleaved
      caspase 3 was observed in Group 1. Conclusions: The saw-tooth appearance was
      likely due to the progressive sequence of laser pulses on the capsule. The low
      energy/high frequency properties of the laser pulse, combined with an overlapped
      pulse pattern, resulted in highly continuous morphology of capsule edges. The
      higher apoptosis induction in FLACS group might be due to photodisruption
      dependent plasma generation and formation of cavitation bubbles.

PMID- 29568764
TI  - Correlation of Serum Uric Acid Levels with Nonculprit Plaque Instability in
      Patients with Acute Coronary Syndromes: A 3-Vessel Optical Coherence Tomography
      Study.
AB  - Elevated serum uric acid (SUA) level is known to be a prognostic factor in
      patients with acute coronary syndrome (ACS). However, the correlation between SUA
      level and coronary plaque instability has not been fully evaluated. The aim of
      this study was to investigate the association between SUA level and plaque
      instability of nonculprit lesions in patients with ACS using optical coherence
      tomography. A total of 150 patients with ACS who underwent 3-vessel optical
      coherence tomography were selected. Patients were classified into 3 groups
      according to tertiles of SUA level. There was a trend towards a thinner fibrous
      cap (0.15 +/- 0.06 versus 0.07 +/- 0.01 versus 0.04 +/- 0.01 mm2, p < 0.001) and
      a wider mean lipid arc (169.41 +/- 33.16 versus 177.22 +/- 37.76 versus 222.43 +/
      47.65 degrees , p < 0.001) with increasing SUA tertile. The plaques of the high
      and intermediate tertile groups had a smaller minimum lumen area than the low
      tertile group (6.02 +/- 1.11 versus 5.38 +/- 1.28 mm2, p < 0.001). In addition,
      thin-cap fibroatheromas, microvessels, macrophages, and cholesterol crystals were
      more frequent in the high tertile group than the low and intermediate groups.
      Multivariate analysis showed SUA level to be a predictor of plaque instability.

PMID- 29568766
TI  - Model Analysis of Digital Models in Moderate to Severe Crowding: In Vivo
      Validation and Clinical Application.
AB  - Objective: We investigated the suitability of intraoral-scan models for measuring
      tooth dimensions and the amount of crowding in patients with severe tooth
      crowding. Materials and Methods: Fifty-eight patients who had undergone intraoral
      scans for diagnosis were included. Cast models were divided into two groups
      depending on the amount of crowding, as determined by initial caliper-based
      measurements (mild crowding [MC] group: <3.0 mm; severe crowding [SC] group: >4.5
      mm). Twenty maxillary models and 20 mandibular models were used in this study.
      For the three types of models (i.e., IS digital model, C cast model, and CS
      digital model), the reproducibility and the precision of linear measurements were
      evaluated. Results: We found that linear measurements made using digital calipers
      on a plaster model and on the relevant software were reproducible. There was no
      significant difference in most linear measurements between digital models and the
      C model. There were differences in the amount of crowding (p < .05), although
      these were not clinically significant. There was no relationship between the
      precision of crowding in the three types of models and the severity of crowding.
      Conclusions: Digital models can be used for measuring crowding in both mild and
      severe crowding cases. However, crowding measured by digital models tends to be
      lesser than that measured by cast models, and this should be considered during
      clinical application.

PMID- 29568765
TI  - The Potential Protective Effect of Curcumin on Amyloid-beta-42 Induced
      Cytotoxicity in HT-22 Cells.
AB  - Background: We aimed to investigate the effect and mechanism of curcumin (CUR) in
      Alzheimer's disease (AD). Methods: Mouse hippocampal neuronal cell line HT-22 was
      treated with Abeta1-42 and/or CUR, and then cell viability was evaluated by cell
      counting kit 8, Beclin-l level was detected using western blotting, and the
      formation of autophagosomes was observed by transmission electron microscopy
      (TEM). Furthermore, transcriptome sequencing and analysis were performed in cells
      with Abeta1-42 alone or Abeta1-42 + CUR. Results: Abeta1-42 treatment
      significantly inhibited cell viability compared with untreated cells (P < 0.01).
      After treatment for 48 h, CUR remarkably promoted cell viability compared with
      cell treated with Abeta1-42 alone (P < 0.01). Compared with cells treated with
      Abeta1-42 alone, the expression of Beclin-1 was slightly reduced in cells with
      combined treatment of Abeta1-42 with CUR (P < 0.05). Consistently, TEM results
      showed that CUR inhibited the formation of autophagosomes in cells treated with
      Abeta1-42. Furthermore, the protein-protein interaction network showed five key
      genes, including MYC, Cdh1, Acaca, Egr1, and CCnd1, likely involved in CUR
      effects. Conclusions: CUR might have a potential neuroprotective effect by
      promoting cell viability in AD, which might be associated with cell autophagy.
      Furthermore, MYC, Cdh1, and Acaca might be involved in the progression of AD.

PMID- 29568768
TI  - Experimental Nanopulse Ablation of Multiple Membrane Parasite on Ex Vivo Hydatid
      Cyst.
AB  - The impact of ultrashort nanopulse on cellular membrane is of biological
      significance and thus has been studied intensively. Different from cell study,
      this ex vivo study aims to investigate the biological effects of nanosecond
      pulsed electric field (nsPEF) on an independent multimembrane parasite, human
      hydatid cyst, to observe the unique influence of nanopulse on macromembrane
      structure, permeabilization, and biochemistry. The 300 ns nsPEF was delivered on
      an experimental model of single human hydatid cyst ex vivo with eight different
      parameters. Then pathological changes during 7 days of 48 parasite cysts were
      followed up after nsPEF. The laminated layer, the germinal layer, the
      protoscolex, and cyst fluid were evaluated by the morphological, pathological,
      and biochemical measurements. The parameter screening found that nsPEF can damage
      hydatid cyst effectively when the field strength is higher than 14 kV/cm. When
      nsPEF is higher than 29 kV/cm, nsPEF destroy hydatid cyst completely by
      collapsing the germinal layer, destructing protoscolices, and exhausting the
      nutrition.

PMID- 29568767
TI  - Construction and Characterization of a Recombinant Human Respiratory Syncytial
      Virus Encoding Enhanced Green Fluorescence Protein for Antiviral Drug Screening
      Assay.
AB  - Human respiratory syncytial virus (RSV) is the single most important cause of
      lower respiratory tract disease in infants and young children and a major viral
      agent responsible for respiratory tract disease in immunosuppressed individuals
      and the elderly, but no vaccines and antiviral drugs are available. Herein the
      recombinant RSV (rRSV) encoding enhanced green fluorescence protein (EGFP, rRSV
      EGFP) was constructed and the potential for screening anti-RSV drugs was
      investigated. The recombinant plasmid of pBRATm-rRSV-EGFP, containing T7
      transcription cassette composed of T7 promoter, RSV antigenomic cDNA with EGFP
      gene, HDV ribozyme (delta), and T7 terminator in the order of 5' to 3', was
      constructed and cotransfected into BHK/T7-9 cells together with helper plasmids
      encoding N, P, L, and M2-1 gene, respectively. The rescued rRSV-EGFP was
      confirmed by increasing expression of EGFP over blind passages and by RT-PCR.
      rRSV-EGFP was comparable to the other two recombinant RSVs encoding red
      fluorescent protein (RFP, rRSV-RFP) or luciferase (Luc, rRSV-Luc) in the growth
      kinetic, and there was a difference in sensitivity between them for screening
      anti-RSV agents based on infection of HEp-2 cells. The EGFP-encoding rRSV has
      been constructed and rescued successfully and has the potential for high
      throughput anti-RSV drug screening in vitro.

PMID- 29568769
TI  - Combination of Constraint-Induced Movement Therapy with Electroacupuncture
      Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in
      Rats.
AB  - Aim: Neonatal hypoxic-ischemia (HI) due to insufficient oxygen supply and blood
      flow during the prenatal and postnatal periods can cause cerebral palsy, a
      serious developmental condition. The purpose of this study was to investigate the
      efficacy of combining constraint-induced movement therapy (CIMT) and
      electroacupuncture to treat rat neonatal HI brain injury. Methods: The left
      common carotid arteries of postnatal day 7 rats were ligated to induce HI brain
      injury, and the neonates were kept in a hypoxia chamber containing 8% oxygen for
      2 hrs. Electroacupuncture at Baihui (GV 20) and Zusanli (ST 36) was performed
      concurrently with CIMT 3 weeks after HI induction for 4 weeks. Results: Motor
      asymmetry after HI was significantly improved in the CIMT and electroacupuncture
      combination group, but HI lesion size was not improved. The combination of CIMT
      and electroacupuncture after HI injury increases NeuN and decreases GFAP levels
      in the cerebral cortex, suggesting that this combination treatment inversely
      regulates neurons and astrocytes. In addition, the combination treatment group
      reduced the level of cleaved caspase-3, a crucial mediator of apoptosis, in the
      cortex. Conclusions: Our findings indicate that a combination of CIMT and
      electroacupuncture is an effective method to treat hemiplegia due to neonatal HI
      brain injury.

PMID- 29568770
TI  - Stromal Cell-Derived Factor-1alpha Alleviates Calcium-Sensing Receptor Activation
      Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced
      Cell Apoptosis in Rat Free Flaps.
AB  - Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury.
      Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1alpha (SDF
      1alpha) are closely associated with myocardial I/R injury. This study was
      performed to evaluate the feasibility of applying SDF-1alpha to counteract CaSR
      activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent
      ischemia for 3 h were equally randomized into five groups: CaCl2, NPS2143 +
      CaCl2, SDF-1alpha + CaCl2, AMD3100 + SDF-1alpha + CaCl2, and normal saline. The
      free flaps were harvested to evaluate flap necrosis and neovascularization after
      2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular
      endothelial cells of free flaps after I/R injury, and activation of the SDF
      1alpha/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3,
      caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was
      true after CaSR activation. Interestingly, initiation of the SDF-1alpha/CXCR4
      axis might abrogate CaSR activation-induced I/R injury through enhancement of
      microvessel density. In conclusion, CaSR might become a novel therapeutic target
      of free flaps affected by I/R injury. Activation of the SDF-1alpha/CXCR4 axis and
      NPS2143 could counteract CaSR activation-mediated I/R injury and promote free
      flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis
      and enhancement of neovascularization.

PMID- 29568771
TI  - Temporal Change of Interleukin-6, C-Reactive Protein, and Skin Temperature after
      Total Knee Arthroplasty Using Triclosan-Coated Sutures.
AB  - The risk of surgical site infections (SSIs) after total knee arthroplasty (TKA)
      can never be eliminated. Antimicrobial sutures containing triclosan have been
      used to decrease SSIs, but whether triclosan-coated sutures are effective with
      TKA is unclear. Between 2011 and 2012, 102 patients randomly assigned to a
      triclosan or a control group were prospectively assessed. The incidence of SSI
      within 3 months of surgery, length of hospital stay, pain scale, functional
      scores, wound condition, and serum inflammatory markers during hospitalization
      and within 3 months postoperatively were compared. At the final follow-up, there
      were 2 patients with superficial infections (3.9%) in the control group but none
      in the triclosan group. Lower serum IL-6 was detected in the triclosan group at 4
      weeks and 3 months. The local skin temperature of the knees-recorded at 3 months
      using infrared thermography-was lower in the triclosan group than in the control
      group. More precise analytical measurements are needed to investigate local and
      systemic complications, especially in the early subclinical stage. This
      prospective, randomized, open-label clinical trial is in the public registry:
      ClinicalTrials.gov (NCT02533492).

PMID- 29568772
TI  - A Two-Step Feature Selection Method to Predict Cancerlectins by Multiview
      Features and Synthetic Minority Oversampling Technique.
AB  - Cancerlectins have an inhibitory effect on the growth of cancer cells and are
      currently being employed as therapeutic agents. The accurate identification of
      the cancerlectins should provide insight into the molecular mechanisms of
      cancers. In this study, a new computational method based on the RF (Random
      Forest) algorithm is proposed for further improving the performance of
      identifying cancerlectins. Hybrid feature space before feature selection is
      developed by combining different individual feature spaces, CTD (Composition,
      Transition, and Distribution), PseAAC (Pseudo Amino Acid Composition), PSSM
      (Position-Specific Scoring Matrix), and disorder. The SMOTE (Synthetic Minority
      Oversampling Technique) is applied to solve the imbalanced data problem. To
      reduce feature redundancy and computation complexity, we propose a two-step
      feature selection process to select informative features. A 5-fold cross
      validation technique is used for the evaluation of various prediction strategies.
      The proposed method achieves a sensitivity of 0.779, a specificity of 0.717, an
      accuracy of 0.748, and an MCC (Matthew's Correlation Coefficient) of 0.497. The
      prediction results are also compared with other existing methods on the same
      dataset using 5-fold cross-validation. The comparison results demonstrate the
      high effectiveness of our method for predicting cancerlectins.

PMID- 29568773
TI  - Does Psychosocial Work Environment Factors Predict Stress and Mean Arterial
      Pressure in the Malaysian Industry Workers?
AB  - Psychosocial risks are considered as a burning issue in the Asia-Pacific region.
      The aim of this study was to investigate the impact of psychosocial work
      environment factors on health of petrochemical industry workers of Malaysia. In
      lieu to job demands-resources theory, significant positive associations were
      found between quantitative demands, work-family conflict, and job insecurity with
      stress, while a significant negative association of role clarity as a resource
      factor with stress was detected. We also found that quantitative demands were
      significantly associated with the mean arterial pressure (MAP). Multistage
      sampling procedure was used to collect study sample. Structural Equation Modeling
      was used to identify relationship between the endogenous and exogenous variables.
      Finally, the empirically tested psychosocial work environment model will further
      help in providing a better risk assessment in different industries and
      enterprises.

PMID- 29568774
TI  - The Timed 180 degrees  Turn Test for Assessing People with Hemiplegia from
      Chronic Stroke.
AB  - Background: Turning is ubiquitous in activities of daily living. For people with
      hemiplegia, persistent impairments in strength, balance, and coordination will
      affect their ability to turn safely. Consequently, turning retraining should be
      addressed in rehabilitation programs. To measure turning for these individuals, a
      reliable clinical tool is required. Objective: To investigate (i) the intrarater,
      interrater, and test-retest reliability of the timed 180 degrees  turn test; (ii)
      the correlation of the timed 180 degrees  turn test with other measures of stroke
      specific impairments; and (iii) the cut-off time that best discriminates
      individuals with hemiplegia from chronic stroke and healthy older adults.
      Methods: 33 individuals with hemiplegia due to chronic stroke and 32 healthy
      elderly individuals participated in this cross-sectional study. The timed 180
      degrees  turn test was administered along with other measures of stroke-specific
      impairment. Results: The timed 180 degrees  turn test demonstrated excellent
      intrarater, interrater, and test-retest reliability in individuals with
      hemiplegia from chronic stroke. The timed 180 degrees  turn test (times)
      significantly correlated with the Fugl-Meyer Assessment of the Lower Extremities
      (FMA-LE), affected ankle plantar flexion strength, the 5-Times-Sit-To-Stand test,
      the Berg Balance Scale (BBS), and the Timed Up and Go (TUG) test. Conclusion: The
      timed 180 degrees  turn test is a reliable clinical tool to assess the turning
      ability of subjects with hemiplegia from chronic stroke.

PMID- 29568775
TI  - The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway
      Indicates Colorectal Carcinogenesis and Prognosis.
AB  - Background: Nucleotide excision repair (NER) plays a critical role in maintaining
      genome integrity. This study aimed to investigate the expression of NER genes and
      their associations with colorectal cancer (CRC) development. Method: Expressions
      of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer
      Genome Atlas (TCGA) data were downloaded to explore relationship of NER
      expression with clinicopathological parameters and survival of CRC. Results:
      ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in
      CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5
      expression indicated deeper T stage and distant metastasis; DDB2 expression
      suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with
      favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression
      was associated with worse overall survival (OS) in colon cancer (HR = 1.53, P =
      0.043). Colon cancer patients with high ERCC4 expression showed favorable OS in
      males (HR = 0.54, P = 0.035). High XPC expression demonstrated decreased death
      hazards in rectal cancer (HR = 0.40, P = 0.026). Conclusion: ERCC1, ERCC2, ERCC4,
      ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2,
      ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of
      CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

PMID- 29568776
TI  - Physical Fitness, Grit, School Attendance, and Academic Performance among
      Adolescents.
AB  - Objective: The purpose of this study was to examine the relationship of grit as a
      construct representing perseverance to overcoming barriers and the total number
      of school absences to academic performance (AP) while controlling for
      sociodemographics, fitness (i.e., PACER), and Body Mass Index (BMI). Methods:
      Adolescents (N = 397, SD = 1.85; 80.9% females; 77.1% Hispanic) from an urban,
      minority-majority city in the Southern United States completed the FitnessGram(r)
      assessment of physical fitness (e.g., aerobic capacity and Body Mass Index (BMI))
      and the valid and reliable short grit survey. The schools provided
      sociodemographics, attendance, and AP data for the adolescents. Results:
      Adolescents with higher grit scores (rs = 0.21, P < 0.001) and less total
      absences (rs = -0.35, P < 0.001) performed better on AP. Hierarchical multiple
      regression indicated that grit and absences were associated with AP (beta = 0.13,
      P < 0.01 and beta = -0.35, P < 0.001, resp.). Conclusions: Grit and a total
      number of absences are significant contributors to academic success, particularly
      among Hispanic adolescents. Further, grit and school attendance may serve as a
      better measure of protective factors over proximal health measures of
      cardiovascular health and BMI.

PMID- 29568777
TI  - Efficient FIR Filter Implementations for Multichannel BCIs Using Xilinx System
      Generator.
AB  - Background. Brain computer interface (BCI) is a combination of software and
      hardware communication protocols that allow brain to control external devices.
      Main purpose of BCI controlled external devices is to provide communication
      medium for disabled persons. Now these devices are considered as a new way to
      rehabilitate patients with impunities. There are certain potentials present in
      electroencephalogram (EEG) that correspond to specific event. Main issue is to
      detect such event related potentials online in such a low signal to noise ratio
      (SNR). In this paper we propose a method that will facilitate the concept of
      online processing by providing an efficient filtering implementation in a
      hardware friendly environment by switching to finite impulse response (FIR). Main
      focus of this research is to minimize latency and computational delay of
      preprocessing related to any BCI application. Four different finite impulse
      response (FIR) implementations along with large Laplacian filter are implemented
      in Xilinx System Generator. Efficiency of 25% is achieved in terms of reduced
      number of coefficients and multiplications which in turn reduce computational
      delays accordingly.

PMID- 29568779
TI  - Evaluating the Difference between Virtual and Paper-Based Clinical Cases in
      Family Medicine Undergraduate Education.
AB  - Introduction: A "virtual patient" is defined as a computer program which
      simulates real patients' cases. The aim of this study was to determine whether
      the inclusion of virtual patients affects the level of factual knowledge of
      family medicine students at the undergraduate level. Methods: This was a case
      controlled prospective study. The students were randomly divided into
      experimental (EG: N = 51) and control (CG: N = 48) groups. The students in the EG
      were asked to practice diagnosis using virtual patients instead of the paper
      based clinical cases which were solved by the students in the CG. The main
      observed variable in the study was knowledge of family medicine, determined by 50
      multiple choice questions (MCQs) about knowledge of family medicine. Results:
      There were no statistically significant differences in the groups' initial
      knowledge. At the final assessment of knowledge, there were no statistically
      significant differences between the groups, but there was a statistically
      significant difference between their initial and final knowledge. Conclusions:
      The study showed that adding virtual patient cases to the curriculum, instead of
      paper clinical cases, did not affect the level of factual knowledge about family
      medicine. Virtual patients can be used, but a significant educational outcome is
      not expected.

PMID- 29568778
TI  - Integration of Routine Parameters of Glycemic Variability in a Simple Screening
      Method for Partial Remission in Children with Type 1 Diabetes.
AB  - Although different criteria were used to define partial remission in type 1
      diabetes, the IDAA1C formula has prevailed as it correlates with stimulated C
      peptide levels. Our retrospective study evaluated clinical variables associated
      with the occurrence of IDAA1C-defined partial remission in a series of 239
      pediatric patients. Diabetic ketoacidosis and age at diagnosis, but no other
      clinical feature, influenced the occurrence of remission. We then evaluated
      whether parameters of glycemic variability used in clinical routine may reliably
      define partial remission, as these would alleviate confounding factors related to
      insulin treatment. Using multiple linear regression, we observed that HbA1C
      levels and percentage of normoglycemia were efficient and sufficient to predict
      partial remission. These parameters were entered into a formula, called glycemic
      target-adjusted HbA1C (GTAA1C), that corresponded to HbA1C(%) - (3 * % of
      normoglycemic values(70-180 mg/dL)). With a threshold of 4.5, this alternative
      formula predicted partial remission with a sensitivity and a specificity of 72.3%
      and 92%, respectively, and yielded strong correlation with IDAA1C levels and BETA
      2 score, which is a correlate of beta-cell function after islet transplantation.
      We propose GTAA1C, based on routine and objective markers of glycemic
      variability, as a valid alternative for definition of partial remission in type 1
      diabetes.

PMID- 29568780
TI  - Drug-Induced Liver Injury: An Institutional Case Series and Review of Literature.
AB  - Drug-induced liver injury (DILI) is the most common cause of acute liver failure
      in the USA. DILI can be broadly classified as Intrinsic and Idiosyncratic.
      Identifying predictors and at-risk patients are challenging but can have a
      substantial clinical implication. This case report series demonstrates the
      importance of valproic acid, fluconazole, and amiodarone as potential hepatoxic
      agents of drug-induced liver injury leading to acute hepatic failure. The
      causality in all cases was established by Roussel Uclaf Causality Assessment
      Method/Council for International Organizations of Medical Sciences score and
      Naranjo Algorithm. Obesity, hypo-perfusion state, and concurrent hepatotoxic
      agent might identify at-risk patients. Further studies are required to understand
      the risk factors.

PMID- 29568781
TI  - Renal Artery Rupture in Association With Fibromuscular Dysplasia.
AB  - Fibromuscular dysplasia is a noninflammatory arteriopathy of unknown etiology
      that affects medium-sized arteries. Although patients affected with it are often
      asymptomatic, some might have recurrent catastrophic events that depend mainly on
      the arterial bed involved. The most worrisome vascular complications of the
      disease are aneurysmal rupture and arterial dissection. Herein, we report a case
      of a 49-year-old woman who presented with sudden-onset abdominal pain without any
      inciting factors. She was found to have active blood extravasation from a
      capsular branch of the renal artery that happened spontaneously. Angiography
      revealed fibromuscular dysplasia in the renal arteries without any obvious
      aneurysms. To our knowledge, this is the first case in the literature describing
      such an event. In this article, we also review the possible underlying pathology
      behind such an event.

PMID- 29568782
TI  - Proteinuria, Hypoalbuminemia, and Chronic Lymphocytic Leukemia: An Unusual Trio.
AB  - Chronic lymphocytic leukemia (CLL) is a chronic, progressive lymphoproliferative
      disorder characterized by a monoclonal population of functionally incompetent
      lymphocytes. Renal involvement is rare and poorly described. A 57-year-old male
      with no prior medical history was diagnosed with CLL and followed with a watch
      and wait approach. He was referred to our institution several months later due to
      concern for Richter's transformation to diffuse large B-cell lymphoma. A positron
      emission tomography/computed tomography scan showed no evidence of diffuse large
      B-cell lymphoma; however, the patient was noted to have hypoalbuminemia,
      nephrotic range proteinuria, an acute left renal vein thrombus, and a right
      pulmonary embolus. A nephrotic syndrome workup including autoimmunity and
      infection was unremarkable, and a kidney biopsy was deferred due to concern for
      renal compromise in the setting of a renal vein thrombus. The patient was treated
      with 6 cycles of reduced-dose fludarabine, cyclophosphamide, and rituximab for a
      presumed CLL-associated nephrotic syndrome and anticoagulation for his venous
      thromboemboli. At 6-month follow-up, the patient achieved complete remission of
      his CLL with normalization of all cell lines and resolution of his nephrotic
      range proteinuria. Repeat computed tomography scans showed no evidence of
      recurrent venous thromboemboli. This case demonstrates a potential role of
      empiric chemotherapy in cases of CLL-associated nephrotic syndrome given its
      potentially life-threatening sequelae and response to treatment.

PMID- 29568783
TI  - Kratom, an Emerging Drug of Abuse, Raises Prolactin and Causes Secondary
      Hypogonadism: Case Report.
AB  - Background. Kratom is a drug derived from the leaves of the tree Mitragyna
      speciose, which is native to southern Thailand. The route of administration is
      oral. Kratom has become increasingly available in the United States. The active
      ingredients in the drug bind the opioid mu-receptor; therefore, kratom has
      similar physiological effects as mu-opioids. Elevated prolactin is a common
      medical condition frequently caused by a variety drugs, including opioids. Case
      Report. A 42-year-old man presented with poor energy and low libido. He had
      mildly elevated serum prolactin with hypogonadotropic hypogonadism as evidenced
      by low serum testosterone with luteinizing hormone and follicle-stimulating
      hormone in the normal range. At his initial visit, he reported no use of any
      recreational or therapeutic drug. Two months later when seen in follow-up, both
      the testosterone and prolactin levels had returned to normal. At that visit he
      reported frequent use of kratom, which he had discontinued a few days after the
      first visit. Discussion. Kratom is now widely available in health food stores and
      online and is considered an emerging drug of abuse. At present kratom is legal in
      the United States, but recently the Drug Enforcement Administration served
      noticed of its intention of making kratom a Schedule I drug. A number of adverse
      events or side effects have been reported, but this is the first report of
      hyperprolactinemia as the result of ingestion of kratom.

PMID- 29568784
TI  - Does the Lever Sign Test Have Added Value for Diagnosing Anterior Cruciate
      Ligament Ruptures?
AB  - Background: Diagnosing an anterior cruciate ligament (ACL) rupture based on a
      physical examination remains a challenge for both surgeons and physical
      therapists. The lever sign test was developed to overcome the practical
      limitations of other tests and to optimize diagnosis. An evaluation of the
      measurement properties of the lever sign test is needed to make adequate
      interpretations in practice. Purpose: To evaluate the reliability and diagnostic
      value of the lever sign test. Study Design: Cohort study (diagnosis); Level of
      evidence, 2. Methods: A total of 94 patients were recruited between November 2014
      and July 2016. Patients were included if they were at least 16 years old,
      suffered from knee trauma, and had indications for knee arthroscopic surgery.
      Lever sign, anterior drawer, Lachman, and pivot-shift test outcomes were examined
      by an orthopaedic/trauma surgeon and a physical therapist. A test-retest design
      was used to investigate interrater reliability. Moreover, the lever sign test
      outcomes, alone and in combination with the other diagnostic tests, were compared
      with arthroscopic results, which served as the gold standard for the test's
      diagnostic value. Results: The lever sign test and pivot-shift test had kappa
      values exceeding 0.80 for interrater reliability. The kappa values for the
      anterior drawer test and Lachman test were 0.80 and 0.77, respectively. The lever
      sign test showed the highest specificity (100%) and the lowest sensitivity (39%)
      when compared with the other 3 tests. Moreover, its positive and negative
      predictive values were 100% and 65%, respectively, while an accuracy of 71% was
      calculated. Clustering the lever sign test parallel with the other 3 tests
      resulted in the highest accuracy of 91%. Conclusion: The lever sign test appears
      to have high interrater reliability and is the most specific test, showing a
      maximal positive predictive value. A positive lever sign test result indicates an
      ACL rupture. These results support the added value of the lever sign test for
      diagnosing ACL ruptures.

PMID- 29568785
TI  - Articular Cartilage Repair of the Knee in Children and Adolescents.
AB  - Articular cartilage predominantly serves a biomechanical function, which begins
      in utero and further develops during growth and locomotion. With regard to its 2
      tissue structure (chondrocytes and matrix), the regenerative potential of hyaline
      cartilage defects is limited. Children and adolescents are increasingly suffering
      from articular cartilage and osteochondral deficiencies. Traumatic incidents
      often result in damage to the joint surfaces, while repetitive microtrauma may
      cause osteochondritis dissecans. When compared with their adult counterparts,
      children and adolescents have a greater capacity to regenerate articular
      cartilage defects. Even so, articular cartilage injuries in this age group may
      predispose them to premature osteoarthritis. Consequently, surgery is indicated
      in young patients when conservative measures fail. The operative techniques for
      articular cartilage injuries traditionally performed in adults may be performed
      in children, although an individualized approach must be tailored according to
      patient and defect characteristics. Clear guidelines for defect dimension
      associated techniques have not been reported. Knee joint dimensions must be
      considered and correlated with respect to the cartilage defect size. Particular
      attention must be given to the subchondral bone, which is frequently affected in
      children and adolescents. Articular cartilage repair techniques appear to be safe
      in this cohort of patients, and no differences in complication rates have been
      reported when compared with adult patients. Particularly, autologous chondrocyte
      implantation has good biological potential, especially for large-diameter joint
      surface defects.

PMID- 29568786
TI  - Reconsidering Return-to-Play Times: A Broader Perspective on Concussion Recovery.
AB  - Background: Return-to-play protocols describe stepwise, graduated recoveries for
      safe return from concussion; however, studies that comprehensively track return
      to-play time are expensive to administer and heavily sampled from elite male
      contact-sport athletes. Purpose: To retrospectively assess probable recovery time
      for collegiate patients to return to play after concussion, especially for
      understudied populations, such as women and nonelite athletes. Study Design:
      Cohort study; Level of evidence, 3. Methods: Medical staff at a military academy
      logged a total of 512 concussion medical records over 38 months. Of these, 414
      records included complete return-to-play protocols with return-to-play time, sex,
      athletic status, cause, and other data. Results: Overall mean return to play was
      29.4 days. Sex and athletic status both affected return-to-play time. Men showed
      significantly shorter return to play than women, taking 24.7 days (SEM, 1.5 days)
      versus 35.5 days (SEM, 2.7 days) (P < .001). Intercollegiate athletes also
      reported quicker return-to-play times than nonintercollegiate athletes: 25.4 days
      (SEM, 2.6 days) versus 34.7 days (SEM, 1.6 days) (P = .002). These variables did
      not significantly interact. Conclusion: Mean recovery time across all groups
      (29.4 days) showed considerably longer return to play than the most commonly
      cited concussion recovery time window (7-10 days) for collegiate athletes.
      Understudied groups, such as women and nonelite athletes, demonstrated notably
      longer recovery times. The diversity of this sample population was associated
      with longer return-to-play times; it is unclear how other population-specific
      factors may have contributed. These inclusive return-to-play windows may indicate
      longer recovery times outside the population of elite athletes.

PMID- 29568787
TI  - Sex-Based Differences in Knee Kinetics With Anterior Cruciate Ligament Strain on
      Cadaveric Impact Simulations.
AB  - Background: Females are at an increased risk of sustaining noncontact knee
      ligament injuries as compared with their male counterparts. The kinetics that
      load the anterior cruciate ligament (ACL) are still under dispute in the
      literature. Purpose/Hypothesis: The purpose of this study was to determine
      whether there are differences in knee kinetics between the sexes that lead to
      greater ACL strain in females when similar external loads are applied during a
      simulated drop vertical jump landing task. It was hypothesized that female limbs
      would demonstrate significant differences in knee abduction moment that
      predispose females to ACL injury when compared with males. Study Design:
      Controlled laboratory study. Methods: Motion analysis data of 67 athletes who
      performed a drop vertical jump were collected. The kinematic and kinetic data
      were used to categorize tertiles of relative risk, and these values were input
      into a cadaveric impact simulator to assess ligamentous loads during the
      simulated landing task. Uni- and multiaxial load cells and differential variable
      reluctance transducer strain sensors were utilized to collect kinetic data and
      maximum ACL strain for analysis. Conditions of external loads applied to the
      cadaveric limbs were systematically varied and randomized. Data were analyzed
      with 2-way repeated-measures analysis of variance and the Fisher exact test.
      Results: Five kinetic parameters were evaluated. Of the 5 kinetic variables, only
      knee abduction moment (KAM) demonstrated significant differences in females as
      compared with males (F1,136 = 4.398, P = .038). When normalized to height and
      weight, this difference between males and females increased in significance
      (F1,136 = 7.155, P = .008). Compared with males, females exhibited a 10.3-N.m
      increased knee abduction torque at 66 milliseconds postimpact and a 22.3-N.m
      increased abduction torque at 100 milliseconds postimpact. For loading condition,
      the condition of "maximum ACL strain" demonstrated a maximum difference of 54.3
      N.m increased abduction torque and 74.5-N.m increased abduction torque at 66
      milliseconds postimpact. Conclusion: Under the tested conditions, increased
      external loads led to increased medial knee translation force, knee abduction
      moment, and external knee moment. Females exhibited greater forces and moments at
      the knee, especially at KAM, when loaded in similar conditions. As these KAM
      loads are associated with increased load and strain on the ACL, the sex-based
      differences observed in the present study may account for a portion of the
      underlying mechanics that predispose females to ACL injury as compared with males
      in a controlled simulated athletic task. Clinical Relevance: KAM increases strain
      to the ACL under clinically representative loading. Additionally, this work
      establishes the biomechanical characteristics of knee loading between sexes.

PMID- 29568788
TI  - Barriers and Facilitators to Colorectal Cancer Screening Among Rural Women in
      Community Clinics by Heath Literacy.
AB  - Background: Rural women lag rural men and urban women in colon cancer (CRC)
      screening completion. Objective: To identify rural female patients' knowledge,
      beliefs barriers, self-efficacy, prior recommendation and completion of CRC
      screening using an FOBT and to compare these factors by health literacy (HL)
      level. Methods: This descriptive study was conducted between 2015 and 2016 in 4
      rural community clinics in south Louisiana. Patients overdue for screening were
      given a structured interview by a research assistant. Results: 339 women were
      enrolled, mean age 58.5, 32% had limited HL, 66% were African American. Most
      (91.7%) had heard of CRC, yet only 71% knew of any CRC screening tests. Women
      with adequate HL had greater knowledge of specific tests than those with limited
      HL (78.4% vs 56.6%, p<0.001). Only 25.7% had been given information on CRC
      testing; those with adequate HL were more likely to have received information
      (30.1% vs 16.8%; p=0.017). Most women (93.2%) indicated they would want to know
      if they had CRC, while 72.2% reported a provider had recommended CRC screening.
      Only 24.9% said a healthcare provider had ever given them an FOBT or that they
      had ever completed an FOBT (22.7%). There were no differences in women's report
      of recommendation or completion by HL level.Self-efficacy for completing an FOBT
      was high; over 90% indicated they could get an FOBT, complete it and mail results
      to the lab. Level of confidence did not vary by literacy. Three of the four
      barrier items varied by HL with women with low HL being more likely to fear doing
      an FOBT because they thought FOBT instructions would be confusing (p=0.002),
      doing the test would be embarrassing (p=0.025) or messy (p=0.057). Conclusions:
      Rural women are receptive to CRC screening and view FOBTs as effective. Rural
      community clinics need to provide low cost FOBTs with literacy, gender and
      culturally appropriate information.

PMID- 29568789
TI  - Ending Cervical Cancer Screening in Low-Risk Women After Age 65: Understanding
      Barriers to Adherence With Evidence-Based Guidelines Among Primary Care
      Providers.
AB  - Background: Current evidence-based cervical cancer testing guidelines recommend
      that screening of low-risk women ceases after age 65. Despite this, research
      suggests that continued testing by primary care providers remains common and
      represents unnecessary patient discomfort, cost, and consumption of valuable
      primary care resources. Objective: To understand why primary care providers might
      knowingly ignore consensus evidence-based screening guidelines for cervical
      cancer in low-risk women of this age-group and to identify barriers to adherence
      with best practice recommendations. Methods: A survey tool to identify barriers
      to adherence with current guidelines for cervical cancer screening in low-risk
      women older than age 65 was mailed to 4929 randomly selected primary care
      providers throughout California. Providers were asked to indicate the predominant
      reason(s) they might knowingly continue cervical cancer screening in women older
      than 65 years, despite evidence-based recommendations to the contrary. Results:
      Qualified surveys were received from 1259 (25.5%) of those surveyed, representing
      primary care providers of all types, practicing in areas of vastly different
      demographics. Despite published reassurance to the contrary, many providers
      retain fear that discontinuation of testing in low-risk women after age 65 may
      result in missed invasive cervical cancer. Even among health-care providers who
      agree that cessation of screening is safe, other circumstances prompt their
      recommendation to continue cervical screening. Conclusion: Although the data from
      this study suggest areas of policy intervention to lessen unnecessary cervical
      cancer screening, the broader implication is that advancement of evidence-based
      medicine will be of little value in improving the quality and cost of health care
      if barriers to guideline adherence are poorly understood and addressed.

PMID- 29568790
TI  - Treatment Changes in General Practice Patients With Chronic Mental Disorders
      Following a Psychiatric-Psychosomatic Consultation.
AB  - Objective: To determine whether a psychiatric-psychosomatic consultation can
      identify unmet treatment needs and improve treatment of patients with mental
      disorders in general practice. Methods: In 40 primary care practices, 307
      consecutive primary patients who met criteria for chronic mental disorders were
      assessed by a psychiatric-psychosomatic consultant. After random assignment,
      general practitioners (GPs) were informed for half of the patients about the
      results of the assessment and received recommendations on how to improve
      treatment. Changes in treatment and patient status were reevaluated after 6
      months. Results: Patients were mostly having depression, adjustment, or anxiety
      disorders, with 28.8% on sick leave. Contact with their respective GPs was longer
      than a year in 77.2% of cases. Patients had already received pharmacotherapy
      (60.9%), psychotherapeutic counseling by GPs themselves (27.7%), psychotherapy by
      specialists (73.9%), psychiatric outpatient care (57%), inpatient psychiatric
      treatment (12.1%), inpatient psychosomatic rehabilitation (ie, specialized
      behavioral medicine facilities for patients with work problems; 41.4%), and a
      broad spectrum of other diagnostic and therapeutic measures. Newly recommended
      interventions included leisure activities (42%), a new specialist psychotherapy
      (37.5%), or inpatient psychosomatic treatment (15.3%). Most recommendations were
      agreed upon by the GP. Nevertheless, there was only a limited increase in
      therapeutic actions 6 months later, and no statistically significant improvement
      in the status of patients. Conclusion: General practitioners undertake a broad
      spectrum of therapeutic interventions in patients with chronic mental disorders.
      According to our results, additional psychiatric-psychosomatic consultations can
      intensify treatment but does not significantly change the general course of
      chronic mental disorders.

PMID- 29568791
TI  - Usefulness of Image Theater Workshops for Exploring Dilemmas in Diabetes Self
      Management Among Adolescents.
AB  - Diabetes treatment involves a demanding self-management regime that is
      particularly challenging to adolescents. There is a need for qualitative research
      into the specific contexts in which adolescents attempt to balance self
      management demands with the needs and desires of adolescent life. This study
      investigates the usefulness of image theater, a participatory form of theater
      using the body as an expressive tool, to articulate these dilemmas in daily life
      contexts. We performed a qualitative analysis of two image theater workshops with
      12- to 18-year-old adolescents living with diabetes. Our results show three areas
      of application: (a) unraveling the contextual complexity of lived experience, (b)
      the articulation of implicit understandings and underlying motives, and (c) the
      playful exploration of new behavior. We conclude that image theater is a
      promising method, especially with respect to the opportunities of a more
      contextual and action-oriented understanding of the trade-offs made in self
      management provide for diabetes education and counseling.

PMID- 29568792
TI  - What Are the Perceptions, Experiences, and Behaviors of Health Care Providers
      After Implementation of a Comprehensive Smoke-Free Hospital Policy?
AB  - The aim of this study was to explore the perceptions, experiences, and behaviors
      of health care providers (HCPs) after the implementation of a comprehensive smoke
      free policy. This qualitative descriptive study, using semi-structured
      interviews, was conducted with 28 HCPs working in a Canadian hospital. Four
      overarching themes emerged from the analysis including (a) greater support for
      tobacco reduction, (b) enhanced patient care and interactions, (c) improved staff
      morale, and (d) some barriers still exist. The main findings suggest a
      comprehensive smoke-free hospital environment can strengthen the tobacco-free
      workplace culture within a hospital setting among HCPs where support for tobacco
      reduction is amplified, patient care and interactions regarding tobacco
      dependence are improved, and staff morale is enhanced. While there are still some
      challenging barriers as well as opportunities for improvements, the
      implementation of a comprehensive smoke-free policy heightened the call-to-action
      among HCPs to take a more active role in tobacco reduction.

PMID- 29568793
TI  - Experiences of Head and Neck Cancer Patients in Middle Adulthood: Consequences
      and Coping.
AB  - The head and neck cancer (HNC) rate is rising among the middle-aged adult
      population. This trend has been attributed primarily to human papillomavirus
      exposure. An HNC diagnosis and its complex treatments may trigger life-changing
      physical, emotional, and social consequences. An interpretive descriptive study
      was conducted to describe the experiences of a purposive sample of 10 middle-aged
      adults who had experienced HNC. Two main themes were identified: consequences of
      HNC and coping with HNC. Subthemes of consequences of HNC included:
      voicelessness; being or looking sick; shifts in family dynamics; and sexual
      practices, sexual feelings, and stigma. Subthemes of coping with HNC included
      seeking information, discovering inner strengths, relying on a support network,
      establishing a sense of normalcy, and finding meaning within the experience.
      Supportive nursing interventions were identified by considering results from the
      standpoint of King's theory of goal attainment.

PMID- 29568794
TI  - Impulsive, Disinhibited Behavior-Dining in a Restaurant.
AB  - Dining in a restaurant with a loved one who has dementia can be an ordeal,
      especially if the expectations of the caregiver do not match those of the patient
      and the restaurant environment is not suitable for patients with dementia. The
      size of the dining area, lighting, background music or noise, decor of the room,
      number of customers, variety of the items on the menu, number of plates and
      cutlery on the table, in addition to flowers, candles, and other decorations on
      the table are all potent distractors. There are so many stimuli; the patient can
      be overwhelmed with information overload and not able to focus on the main
      purpose of the event: have dinner and especially enjoy the other person's
      company. In this case scenario, we present a 62-year-old man diagnosed with
      behavioral variant frontotemporal dementia (bvFTD). His daughter "invited" him to
      have dinner with her at a very fancy restaurant to celebrate her promotion at
      work. Unfortunately, whereas the evening started very well, it had a catastrophic
      ending. We discuss what went wrong in the patient/daughter interaction and how
      the catastrophic ending could have been avoided or averted.

PMID- 29568795
TI  - Mediator Effect of Balance Problems on Association Between Grip Strength and
      Falls in Older Adults: Results From the KORA-Age Study.
AB  - Objective: To examine the association between grip strength and history of falls
      among older individuals, and to assess the possible mediating effect of balance
      problems on this relationship. Method: Data originate from KORA (Cooperative
      Health Research in the Region of Augsburg)-Age Study of 808 individuals (65 years
      and above). Follow-up assessment occurred 3 years later. Results: The risk of
      falls within the last 12 months was reduced on average by 3% (odds ratio [OR] 95%
      confidence interval [95% CI] = 0.97 [0.94, 0.99]; p value = .026) per 1-kg
      increase in maximum grip strength after adjusting for age and gender. There was a
      trend toward an indirect effect of grip strength through the mediator variable
      balance problems (p value = .043). Discussion: Increased muscular strength is
      associated with a reduced risk of falls in older age after adjustment for age and
      gender. The association is partially mediated by balance problems. Thus, in older
      adults, muscle-strengthening exercises may decrease the risk of falling.

PMID- 29568796
TI  - Desaturation During Cry in the Neonatal Period.

PMID- 29568797
TI  - Effects of consumption of whole grape powder on basal NF-kappaB signaling and
      inflammatory cytokine secretion in a mouse model of inflammation.
AB  - Dietary consumption of polyphenol-rich fruits, such as grapes, may reduce
      inflammation and potentially prevent diseases linked to inflammation. Here, we
      used a genetically engineered murine model to measure Nuclear Factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB) activity and pro-inflammatory
      cytokine secretion to test the hypothesis that oral consumption of whole grape
      formulation reduces inflammatory signaling in the body. NF-kappaB luciferase
      reporter mice were divided into two groups, one which was fed an experimental
      diet formulated with 4% (w/w) whole grape powder (WGP) or another which was fed a
      control diet formulated with 3.6% glucose/fructose (w/w) combination. Simulated
      inflammation was induced in the mice by intraperitoneal injection of
      lipopolysaccharide (LPS). In vivo imaging was used to determine the effect of
      each diet on NF-kappaB activity. We found that there were no significant
      differences in weight gain between the WGP and control diet groups. However,
      there was a statistically significant (p<0.0001) difference in the progression of
      basal levels of NF-kappaB signaling between mice fed on control or WGP diet.
      There were no significant differences in NF-kappaB reporter indices between WGP-
      and control-diet groups after either acute or repeated inflammatory challenge.
      However, terminal blood collection revealed significantly (p<0.01) lower serum
      concentrations of the inflammatory cytokines Interleukin-6 (IL-6) and Tumor
      Necrosis Factor alpha (TNFalpha) only among WGP diet mice subjected to acute
      inflammatory challenge. Overall, these data suggest that while diets supplemented
      with WGP may suppress steady-state low levels of inflammatory signaling, such a
      supplementation may not alleviate exogenously induced massive NF-kappaB
      activation.

PMID- 29568798
TI  - Encoding of Spatial Attention by Primate Prefrontal Cortex Neuronal Ensembles.
AB  - Single neurons in the primate lateral prefrontal cortex (LPFC) encode information
      about the allocation of visual attention and the features of visual stimuli.
      However, how this compares to the performance of neuronal ensembles at encoding
      the same information is poorly understood. Here, we recorded the responses of
      neuronal ensembles in the LPFC of two macaque monkeys while they performed a task
      that required attending to one of two moving random dot patterns positioned in
      different hemifields and ignoring the other pattern. We found single units
      selective for the location of the attended stimulus as well as for its motion
      direction. To determine the coding of both variables in the population of
      recorded units, we used a linear classifier and progressively built neuronal
      ensembles by iteratively adding units according to their individual performance
      (best single units), or by iteratively adding units based on their contribution
      to the ensemble performance (best ensemble). For both methods, ensembles of
      relatively small sizes (n < 60) yielded substantially higher decoding performance
      relative to individual single units. However, the decoder reached similar
      performance using fewer neurons with the best ensemble building method compared
      with the best single units method. Our results indicate that neuronal ensembles
      within the LPFC encode more information about the attended spatial and nonspatial
      features of visual stimuli than individual neurons. They further suggest that
      efficient coding of attention can be achieved by relatively small neuronal
      ensembles characterized by a certain relationship between signal and noise
      correlation structures.

PMID- 29568799
TI  - Susceptibility to Oxidative Stress Is Determined by Genetic Background in
      Neuronal Cell Cultures.
AB  - Traumatic brain injury (TBI) leads to a deleterious and multifactorial secondary
      inflammatory response in the brain. Oxidative stress from the inflammation likely
      contributes to the brain damage although it is unclear to which extent. A largely
      unexplored approach is to consider phenotypic regulation of oxidative stress
      levels. Genetic polymorphism influences inflammation in the central nervous
      system and it is possible that the antioxidative response differs between
      phenotypes and affects the severity of the secondary injury. We therefore
      compared the antioxidative response in inbred rat strains dark agouti (DA) to
      piebald viral glaxo (PVG). DA has high susceptibility to inflammatory challenges
      and PVG is protected. Primary neuronal cell cultures were exposed to
      peroxynitrite (ONOO-), nitric oxide (NO), superoxide (O2-), and 4-hydroxynonenal
      (4-HNE). Our findings demonstrated a phenotypic control of the neuronal
      antioxidative response, specific to manganese O2- dismutase (MnSOD). DA neurons
      had increased levels of MnSOD, equal levels of peroxiredoxin 5 (PRDX5), decreased
      oxidative stress markers 3-nitrotyrosine (3-NT) and 4-HNE and decreased neuronal
      death detected by lactate dehydrogenase (LDH) release after 24 h, and higher
      oxidative stress levels by CellROX than PVG after 2 h. It is possible that DA
      neurons had a phenotypic adaptation to a fiercer inflammatory environment. ONOO-
      was confirmed as the most powerful oxidative damage mediator, while 4-HNE caused
      few oxidative effects. Inducible NO synthase (iNOS) was not induced, suggesting
      that inflammatory, while not oxidative stimulation was required. These findings
      indicate that phenotypic antioxidative regulation affects the secondary
      inflammation, which should be considered in future individualized treatments and
      when evaluating antioxidative pharmacological interventions.

PMID- 29568800
TI  - Metamorphic records of multiple seismic cycles during subduction.
AB  - Large earthquakes occur in rocks undergoing high-pressure/low-temperature
      metamorphism during subduction. Rhythmic major-element zoning in garnet is a
      common product of such metamorphism, and one that must record a fundamental
      subduction process. We argue that rhythmic major-element zoning in subduction
      zone garnets from the Franciscan Complex, California, developed in response to
      growth-dissolution cycles driven by pressure pulses. Using electron probe
      microanalysis and novel techniques in Raman and synchrotron Fourier transform
      infrared microspectroscopy, we demonstrate that at least four such pressure
      pulses, of magnitude 100-350 MPa, occurred over less than 300,000 years. These
      pressure magnitude and time scale constraints are most consistent with the garnet
      zoning having resulted from periodic overpressure development-dissipation cycles,
      related to pore-fluid pressure fluctuations linked to earthquake cycles. This
      study demonstrates that some metamorphic reactions can track individual
      earthquake cycles and thereby opens new avenues to the study of seismicity.

PMID- 29568801
TI  - Bats without borders: Predators learn novel prey cues from other predatory
      species.
AB  - Learning from others allows individuals to adapt rapidly to environmental change.
      Although conspecifics tend to be reliable models, heterospecifics with similar
      resource requirements may be suitable surrogates when conspecifics are few or
      unfamiliar with recent changes in resource availability. We tested whether
      Trachops cirrhosus, a gleaning bat that localizes prey using their mating calls,
      can learn about novel prey from conspecifics and the sympatric bat Lophostoma
      silvicolum. Specifically, we compared the rate for naive T. cirrhosus to learn an
      unfamiliar tone from either a trained conspecific or heterospecific alone through
      trial and error or through social facilitation. T. cirrhosus learned this novel
      cue from L. silvicolum as quickly as from conspecifics. This is the first
      demonstration of social learning of a novel acoustic cue in bats and suggests
      that heterospecific learning may occur in nature. We propose that auditory-based
      social learning may help bats learn about unfamiliar prey and facilitate their
      adaptive radiation.

PMID- 29568802
TI  - Evidence of Early Emergence of the Primary Dentition in a Northern Plains
      American Indian Population.
AB  - The purposes of this study were to describe primary tooth emergence in an
      American Indian (AI) population during the first 36 mo of life to compare 1)
      patterns of emergence between male and female children and 2) tooth emergence
      between these AI children and other U.S. ethnic groups. Data were derived from a
      birth cohort of 239 AI children from a Northern Plains tribe participating in a
      longitudinal study of early childhood caries, with examination data at target
      ages of 8, 12, 16, 22, 28, and 36 mo of age (+/-1 mo). Patterns of emergence in
      AI children were characterized and sex comparisons accomplished with interval
      censored survival methodology. Numbers of erupted teeth in AI children at each
      age were compared via Kruskal-Wallis tests against those in children of the same
      age, as drawn from a cross-sectional study of dental caries patterns in Arizona;
      these comparisons were based on the dental examinations of 547 White non-Hispanic
      and 677 Hispanic children. Characterization of time to achievement of various
      milestones-including emergence of the anterior teeth, the first molars, and the
      complete primary dentition-provided no evidence of sex differences among AI
      children. AI children had significantly more teeth present at 8 mo (median, 3)
      than either White non-Hispanic (P < 0.0063) or Hispanic (P < 0.0001) children
      (median, 2 each). This was also true at 12 mo (P < 0.001; medians, 8 vs. 6 and 7,
      respectively) and 16 mo (P < 0.001; medians, 12 vs. 11 each). Less pronounced
      differences were seen at 22 mo (P < 0.0001). White non-Hispanic and Hispanic
      children did not differ at any time considered (P > 0.05). These results provide
      evidence of earlier tooth emergence in AI children than in the other 2
      ethnicities. Although the underlying etiology of the severity of early childhood
      caries in AI children is likely to be multifactorial, earlier tooth emergence may
      be a contributing factor. Knowledge Transfer Statement: The findings of this
      study have practical implications for practitioners providing childhood oral
      health care to ethnic groups with early tooth emergence. It may be important to
      provide parents with information on toothbrushing, dentist visits, and other
      practices supportive of good oral health as early as possible to protect their
      children's primary dentition.

PMID- 29568803
TI  - School-Based Caries Prevention, Tooth Decay, and the Community Environment.
AB  - The school and community context can contribute to inequity in child oral health.
      Whether the school and community affect the effectiveness of school-based caries
      prevention is unknown. The association between the school and community
      environment and dental caries, as well as their moderating effects with school
      based caries prevention, was assessed using multilevel mixed-effects regression.
      Data were derived from a 6-y prospective cohort study of children participating
      in a school-based caries prevention program. For the school and community, living
      in a dental-shortage area and the proportion of children receiving free or
      reduced lunch were significantly related to an increased risk of dental caries at
      baseline. Caries prevention was associated with a significant per-visit decrease
      in the risk of untreated caries, but the rate of total caries experience
      increased over time. Caries prevention was more effective in children who had
      prior dental care at baseline and in schools with a higher proportion of low
      socioeconomic status students. There was significant variation across schools in
      the baseline prevalence of dental caries and the effect of prevention over time,
      although effects were modest. The school and community environment have a direct
      impact on oral health and moderate the association between school-based caries
      prevention and dental caries. Knowledge Transfer Statement: School-based caries
      prevention can be an effective means to reduce oral health inequity by embedding
      dental care within schools. However, the socioeconomic makeup of schools and
      characteristics of the surrounding community can affect the impact of school
      based care.

PMID- 29568804
TI  - Screening for Diabetes Risk Using Integrated Dental and Medical Electronic Health
      Record Data.
AB  - Undiagnosed diabetes and prediabetes present a serious public health challenge.
      We previously reported that data available in the dental setting can serve as a
      tool for early dysglycemia identification in a primarily Hispanic, urban
      population. In the present study, we sought to determine how the identification
      approach can be recalibrated to detect diabetes or prediabetes in a White, rural
      cohort and whether an integrated dental-medical electronic health record (iEHR)
      offers further value to the process. We analyzed iEHR data from the Marshfield
      Clinic, a health system providing care in rural Wisconsin, for dental patients
      who were >=21 y of age, reported that they had never been told they had diabetes,
      had an initial periodontal examination of at least 2 quadrants, and had a
      glycemic assessment within 3 mo of that examination. We then assessed the
      performance of multiple predictive models for prediabetes/diabetes. The study
      outcome, glycemic status, was gleaned from the medical module of the iEHR based
      on American Diabetes Association blood test cutoffs. The sample size was 4,560
      individuals. Multivariate logistic regression revealed that the best performance
      was achieved by a model that took advantage of the iEHR. Predictors included age,
      sex, race, ethnicity, number of missing teeth, percentage of teeth with at least
      1 pocket >=5 mm from the dental EHR, and overweight/obesity, hypertension,
      hyperlipidemia, and smoking status from the medical EHR. The model achieved an
      area under the receiver operating characteristic curve of 0.71 (95% confidence
      interval, 0.69-0.72), yielding a sensitivity of 0.70 and a specificity of 0.62.
      Across a range of populations, informed by certain patient characteristics,
      dental care team members can play a role in helping to identify dental patients
      with undiagnosed diabetes or prediabetes. The accuracy of the prediction
      increases when dental findings are combined with information from the medical
      EHR. Knowledge Transfer Statement: Prediabetes and diabetes often go undiagnosed
      for many years. Early identification and care can lead to improved glycemic
      outcomes and prevent wide-ranging morbidity, including adverse oral health
      consequences, in affected individuals. Information available in the dental office
      can be used by clinicians to identify those who remain undiagnosed or are at
      risk; the accuracy of this prediction increases when combined with information
      from the medical electronic health record.

PMID- 29568805
TI  - Status and determinants of health services utilization among elderly migrants in
      China.
AB  - Background: The household registration system in China places migrants in a
      vulnerable status regarding access to local public services, including limited
      access to health services. Most studies on migrants' health services utilization
      targeted on working-age migrants, and there has been a paucity of studies
      conducted among elderly migrants. This study aims to investigate the status of
      health services utilization and its influential factors among elderly migrants.
      Methods: Data (13,043 participants, 52.4% male, mean age 66.22 +/- 6.20) were
      derived from the 2015 Migrant Dynamics Monitoring Survey. The outcome variable in
      the study was health services utilization, consisting of doctor visits,
      hospitalization and local inpatient care. The Behavioral Model of Health Service
      Use was applied to categorize the influential factors into three components,
      including predisposing, enabling and need factors. Multivariate logistic
      regression analysis was used to investigate the influential factors of the three
      components of health services utilization. Results: Of the total sample, 45.5%
      would visit a doctor when they were ill, 81.8% would prefer to be hospitalized
      when recommended by doctors, and 71.6% (those who were hospitalized) would choose
      to receive local inpatient care rather than going back to their hometown. Age,
      marital status, household income, years of residence, migration range, reasons
      for migration, size of friend network, health insurance type, local health
      insurance status and chronic disease status were significantly associated with
      health services utilization. Conclusion: A low level of local health services
      utilization was observed among elderly migrants. Enabling factors played
      important roles in promoting health services utilization among elderly migrants.
      Policy and decision makers may consider improving the capability for elderly
      migrants to access health services, such as increasing income and providing local
      health insurance.

PMID- 29568806
TI  - Antibiotic resistance patterns of urinary tract pathogens in Turkish children.
AB  - Background: Knowledge of local antimicrobial resistance patterns is essential for
      evidence- based empirical antibiotic prescribing. We aimed to investigate the
      distribution and changes in causative agents of urinary tract infections in
      children and the resistance rates, and to recommend the most appropriate
      antibiotics. Methods: In this retrospective study, we evaluated causative agents
      and antimicrobial resistance in urine isolates from the positive community from
      September 2014 to April 2016 in a single hospital in Ankara, Turkey. Results: A
      total of 850 positive urine cultures were identified, of which 588 (69.2%) were
      from girls and 262 (30.8%) were from boys. Their mean age was 36.5 +/- 45.0
      months. The most common causative agent was Escherichia coli (64.2% of cases)
      followed by Klebsiella pneumoniae (14.9%). The overall resistance to ampicillin
      (62.6%), cephalothin (44.2%), co-trimoxazole (29.8%) and cefuroxime (28.7%) was
      significant. No resistance to imipenem was detected in the isolates. The least
      resistance was for amikacin, ceftriaxone, ciprofloxacin and cefepime (0.1, 2.4,
      7.5 and 8.3%, respectively). Imipenem was the most active agent against E. coli
      followed by amikacin (0.2%), ceftriaxone (2.7%) and nitrofurantoin (5.1%). High
      resistance rates to nitrofurantoin were detected in K. pneumoniae, Proteus and
      Enterobacteriae. Conclusions: E. coli was the most common causative agent of
      urinary tract infection in children. Ampicillin, trimethoprim-sulfometaxazole,
      cephalothin and cefuroxim had the highest resistance rates against urinary tract
      pathogens in our center. For oral empirical antibiotherapy, cefixime is the most
      appropriate choice so as to include Klebsiella strains.

PMID- 29568807
TI  - The age of heterozygous telomerase mutant parents influences the adult phenotype
      of their offspring irrespective of genotype in zebrafish.
AB  - BACKGROUND: Mutations in proteins involved in telomere maintenance lead to a
      range of human diseases, including dyskeratosis congenita, idiopathic pulmonary
      fibrosis and cancer. Telomerase functions to add telomeric repeats back onto the
      ends of chromosomes, however non-canonical roles of components of telomerase have
      recently been suggested. METHODS: Here we use a zebrafish telomerase mutant which
      harbours a nonsense mutation in tert to investigate the adult phenotypes of fish
      derived from heterozygous parents of different ages. Furthermore we use whole
      genome sequencing data to estimate average telomere lengths. RESULTS: We show
      that homozygous offspring from older heterozygotes exhibit signs of body wasting
      at a younger age than those of younger parents, and that offspring of older
      heterozygous parents weigh less irrespective of genotype. We also demonstrate
      that tert homozygous mutant fish have a male sex bias, and that clutches from
      older parents also have a male sex bias in the heterozygous and wild-type
      populations. Telomere length analysis reveals that the telomeres of younger
      heterozygous parents are shorter than those of older heterozygous parents.
      CONCLUSIONS: These data indicate that the phenotypes observed in offspring from
      older parents cannot be explained by telomere length. Instead we propose that
      Tert functions outside of telomere length maintenance in an age-dependent manner
      to influence the adult phenotypes of the next generation.

PMID- 29568808
TI  - Small-scale field evaluation of push-pull system against early- and outdoor
      biting malaria mosquitoes in an area of high pyrethroid resistance in Tanzania.
AB  - Background: Despite high coverage of indoor interventions like insecticide
      treated nets, mosquito-borne infections persist, partly because of outdoor
      biting, early-biting and insecticide-resistant vectors. Push-pull systems, where
      mosquitoes are repelled from humans and attracted to nearby lethal targets, may
      constitute effective complementary interventions. Methods: A partially randomized
      cross-over design was used to test efficacy of push-pull in four experimental
      huts and four local houses, in an area with high pyrethroid resistance in
      Tanzania. The push-pull system consisted of 1.1% or 2.2% w/v transfluthrin
      repellent dispensers and an outdoor lure-and-kill device (odour-baited mosquito
      landing box). Matching controls were set up without push-pull. Adult male
      volunteers collected mosquitoes attempting to bite them outdoors, but collections
      were also done indoors using exit traps in experimental huts and by volunteers in
      the local houses. The collections were done hourly (1830hrs-0730hrs) and mosquito
      catches compared between push-pull and controls. An. gambiae s.l. and An.
      funestus s.l. were assessed by PCR to identify sibling species, and ELISA to
      detect Plasmodium falciparum and blood meal sources. Results: Push-pull in
      experimental huts reduced outdoor-biting for An. arabiensis and Mansonia species
      by 30% and 41.5% respectively. However, the reductions were marginal and
      insignificant for An. funestus (12.2%; p>0.05) and Culex (5%; p>0.05). Highest
      protection against all species occurred before 2200hrs. There was no significant
      difference in number of mosquitoes inside exit traps in huts with or without push
      pull. In local households, push-pull significantly reduced indoor and outdoor
      biting of An. arabiensis by 48% and 25% respectively, but had no effect on other
      species. Conclusion: This push-pull system offered modest protection against
      outdoor-biting An. arabiensis, without increasing indoor mosquito densities.
      Additional experimentation is required to assess how transfluthrin-based products
      affect mosquito blood-feeding and mortality in push-pull contexts. This approach,
      if optimised, could potentially complement existing malaria interventions even in
      areas with high pyrethroid resistance.

PMID- 29568809
TI  - Effects of engineered nanomaterial exposure on macrophage innate immune function.
AB  - Increasing use of engineered nanomaterials (ENMs) means increased human
      exposures. Potential adverse effects include those on the immune system, ranging
      from direct toxicity to impairment of defenses against environmental pathogens
      and toxins. Effects on lung macrophages may be especially prominent, because they
      serve to clear foreign materials like ENMs and bacterial pathogens. We
      investigated the effects of 4 hour exposures over a range of concentrations, of a
      panel of industry-relevant ENMs, including SiO2, Fe2O3, ZnO, CeO2, TiO2, and an
      Ag/SiO2 composite, on human THP-1 macrophages. Effects on phagocytosis of latex
      beads, and phagocytosis and killing of Francisella tularensis (FT), as well as
      viability, oxidative stress and mitochondrial integrity, were measured by
      automated scanning confocal microscopy and image analysis. Results revealed some
      notable patterns: 1) Phagocytosis of unopsonized beads was increased, whereas
      that of opsonized beads was decreased, by all ENMs, with the exception of ZnO,
      which reduced both opsonized and unopsonized uptake; 2) Uptake of opsonized and
      unopsonized FT was either impaired or unaffected by all ENMs, with the exception
      of CeO2, which increased phagocytosis of unopsonized FT; 3) Macrophage killing of
      FT tended to improve with all ENMs; and 4) Viability was unaffected immediately
      following exposures with all ENMs tested, but was significantly decreased 24
      hours after exposures to Ag/SiO2 and ZnO ENMs. The results reveal a complex
      landscape of ENM effects on macrophage host defenses, including both enhanced and
      reduced capacities, and underscore the importance of robust hazard assessment,
      including immunotoxicity assessment, of ENMs.

PMID- 29568810
TI  - The Role of the Food Matrix and Gastrointestinal Tract in the assessment of
      biological properties of ingested engineered nanomaterials (iENMs): State of the
      science and knowledge gaps.
AB  - Many foods contain appreciable levels of engineered nanomaterials (ENMs)
      (diameter < 100 nm) that may be either intentionally or unintentionally added.
      These ENMs vary considerably in their compositions, dimensions, morphologies,
      physicochemical properties, and biological responses. From a toxicological point
      of view, it is often convenient to classify ingested ENMs (iENMs) as being either
      inorganic (such as TiO2, SiO2, Fe2O3, or Ag) or organic (such as lipid, protein,
      or carbohydrate), since the former tend to be indigestible and the latter are
      generally digestible. At present there is a relatively poor understanding of how
      different types of iENMs behave within the human gastrointestinal tract (GIT),
      and how the food matrix and biopolymers transform their physico-chemical
      properties and influence their gastrointestinal fate. This lack of knowledge
      confounds an understanding of their potential harmful effects on human health.
      The purpose of this article is to review our current understanding of the GIT
      fate of iENMs, and to highlight gaps where further research is urgently needed in
      assessing potential risks and toxicological implications of iENMs. In particular,
      a strong emphasis is given to the development of standardized screening methods
      that can be used to rapidly and accurately assess the toxicological properties of
      iENMs.

PMID- 29568811
TI  - Oxidative Stress and Metabolic Reprogramming in Cr(VI) Carcinogenesis.
AB  - Cr(VI)-containing compounds are well-established lung carcinogens. Chronic
      exposure of the normal human epithelial cells is able to induce malignant cell
      transformation, the first stage of metal carcinogenesis. These Cr(VI)-transformed
      cells exhibit increased level of antioxidants, reduced capacity of generating
      reactive oxygen species (ROS), and development of apoptosis resistance, promoting
      tumorigenesis of Cr(VI)-transformed cells, the second stage of metal
      carcinogenesis. The mechanism of Cr(VI) induced carcinogenesis is still under
      investigation. Recent studies indicate that ROS play a positive role in the first
      stage while a negative role in the second stage. Transformed cells adapt
      metabolism to support tumor initiation and progression. Altered metabolic
      activities directly participate in the process of cell transformation or support
      a large requirement for nucleotides, amino acids, and lipids for tumor growth. In
      malignantly Cr(VI)-transformed cells, mitochondrial oxidative phosphorylation is
      defective, and pentose phosphate pathway, glycolysis, and glutaminolysis are
      upregulated. These metabolic reprogramming supports rapid cell proliferation and
      contributes to tumorigenesis of Cr(VI)-transformed cells. This article summarizes
      the current progress in the studies of metabolic reprogramming and Cr(VI)
      carcinogenesis with emphasis on the metabolic enzymes and oxidative stress
      related major oncogenic pathways.

PMID- 29568813
TI  - Hypoglycemia in a Patient With a Polyhormonal Pancreatic Neuroendocrine Tumor
      With Evidence of Endocrine Progenitors.
AB  - A 55-year-old woman with a large polyhormonal neuroendocrine tumor with unusual
      pathology is described. The patient presented with intermittent neuroglycopenic
      symptoms between more protracted asymptomatic periods occurring over the
      preceding 4 years. During a diagnostic 72-hour inpatient fast, she exhibited
      hypoglycemia at 70 hours after initiation. On computed tomography scan, a 6-cm
      mass was identified at the pancreatic head. The patient underwent a pylorus
      preserving pancreaticoduodenectomy, and pathology was positive for cells staining
      for pancreatic polypeptide, insulin, and occasional double hormone (insulin plus
      pancreatic polypeptide)-positive cells. In addition, the tumor exhibited broad
      staining for ALDH1A3, a new marker of endocrine progenitors. This case serves to
      highlight the clinical and pathologic variability of insulin-producing tumors and
      raises the potential for cells in these tumors to exhibit hormone interconversion
      and progenitor-like states.

PMID- 29568812
TI  - Retinoic acid-related Orphan Receptor gamma (RORgamma): connecting sterol
      metabolism to regulation of the immune system and autoimmune disease.
AB  - Cholesterol and its metabolites are bioactive lipids that interact with and
      regulate the activity of various proteins and signaling pathways that are
      implicated in the control of a variety of physiological and pathological
      processes. Recent studies revealed that retinoic acid-related orphan receptors,
      RORalpha and gamma, members of the ligand-dependent nuclear receptor superfamily,
      exhibit quite a wide binding specificity for a number of sterols. Several
      cholesterol intermediates and metabolites function as natural ligands of RORalpha
      and RORgamma and act as agonists or inverse agonists. Changes in cholesterol
      homeostasis that alter the level or type of sterol metabolites in cells, can
      either enhance or inhibit ROR transcriptional activity that subsequently result
      in changes in the physiological processes regulated by RORs, including various
      immune responses and metabolic pathways. Consequently, this might negatively or
      positively impact pathologies, in which RORs are implicated, such as autoimmune
      disease, inflammation, metabolic syndrome, cancer, and several neurological
      disorders. Best studied are the links between cholesterol metabolism, RORgammat
      activity, and their regulation of Th17 differentiation and autoimmune disease.
      The discovery that Th17-dependent inflammation is significantly attenuated in
      RORgamma-deficient mice in several experimental autoimmune disease models,
      initiated a search for ROR modulators that led to the identification of a number
      of small molecular weight RORgamma inverse agonists. The inverse agonists
      suppress Th17 differentiation and IL-17 production and protect against
      autoimmunity. Together, these studies suggest that RORgammat may provide an
      attractive therapeutic target in the management of several (inflammatory)
      diseases.

PMID- 29568814
TI  - GLP-1 and Insulin Recruit Muscle Microvasculature and Dilate Conduit Artery
      Individually But Not Additively in Healthy Humans.
AB  - Context: Glucagon-like peptide-1 (GLP-1) and insulin increase muscle
      microvascular perfusion, thereby increasing tissue endothelial surface area and
      nutrient delivery. Objective: To examine whether GLP-1 and insulin act additively
      on skeletal and cardiac microvasculature and conduit artery. Design: Healthy
      adults underwent three study protocols in random order. Setting: Clinical
      Research Unit at the University of Virginia. Methods: Overnight-fasted
      participants received an intravenous infusion of GLP-1 (1.2 pmol/kg/min) or
      normal saline for 150 minutes with or without a 2-hour euglycemic insulin clamp
      (1 mU/kg/min) superimposed from 30 minutes onward. Skeletal and cardiac muscle
      microvascular blood volume (MBV), flow velocity, and flow; brachial artery
      diameter, flow velocity, and blood flow; and pulse wave velocity (PWV) were
      measured. Results: GLP-1 significantly increased skeletal and cardiac muscle MBV
      and microvascular blood flow (MBF) after 30 minutes; these remained elevated at
      150 minutes. Insulin also increased skeletal and cardiac muscle MBV and MBF.
      Addition of insulin to GLP-1 did not further increase skeletal and cardiac muscle
      MBV and MBF. GLP-1 and insulin increased brachial artery diameter and blood flow,
      but this effect was not additive. Neither GLP-1, insulin, nor GLP-1 and insulin
      altered PWV. Combined GLP-1 and insulin infusion did not result in higher whole
      body glucose disposal. Conclusion: GLP-1 and insulin at physiological
      concentrations acutely increase skeletal and cardiac muscle microvascular
      perfusion and dilate conduit artery in healthy adults; these effects are not
      additive. Thus, GLP-1 and insulin may regulate skeletal and cardiac muscle
      endothelial surface area and nutrient delivery under physiological conditions.

PMID- 29568817
TI  - Biological Interpretation of Morphological Patterns in Histopathological Whole
      Slide Images.
AB  - We propose a framework for studying visual morphological patterns across
      histopathological whole-slide images (WSIs). Image representation is an important
      component of computer-aided decision support systems for histopathological cancer
      diagnosis. Such systems extract hundreds of quantitative image features from
      digitized tissue biopsy slides and produce models for prediction. The performance
      of these models depends on the identification of informative features for
      selection of appropriate regions-of-interest (ROIs) from heterogeneous WSIs and
      for development of models. However, identification of informative features is
      hindered by the semantic gap between human interpretation of visual morphological
      patterns and quantitative image features. We address this challenge by using data
      mining and information visualization tools to study spatial patterns formed by
      features extracted from sub-sections of WSIs. Using ovarian serous
      cystadenocarcinoma (OvCa) WSIs provided by the cancer genome atlas (TCGA), we
      show that (1) individual and (2) multivariate image features correspond to
      biologically relevant ROIs, and (3) supervised image feature selection can map
      histopathology domain knowledge to quantitative image features.

PMID- 29568816
TI  - A Major Population of Functional KLRG1- ILC2s in Female Lungs Contributes to a
      Sex Bias in ILC2 Numbers.
AB  - Humans show significant sex differences in the incidence and severity of
      respiratory diseases, including asthma and virus infection. Sex hormones
      contribute to the female sex bias in type 2 inflammation associated with
      respiratory diseases, consistent with recent reports that female lungs harbor
      greater numbers of GATA-3-dependent group 2 innate lymphoid cells (ILC2s). In
      this study, we determined whether sex hormone levels govern sex differences in
      the numbers, phenotype, and function of ILC2s in the murine lung and bone marrow
      (BM). Our data show that lungs of female mice harbor significantly greater ILC2
      numbers in homeostasis, in part due to a major subset of ILC2s lacking killer
      cell lectin like receptor G1 (KLRG1), a population largely absent in male lungs.
      The KLRG1- ILC2s were capable of type 2 cytokine production and increased with
      age after sexual maturity, suggesting that a unique functional subset exists in
      females. Experiments with gonadectomized mice or mice bearing either global or
      lymphocyte restricted estrogen receptor alpha (Esr1) deficiency showed that
      androgens rather than estrogens regulated numbers of the KLRG1- ILC2 subset and
      ILC2 functional capacity in the lung and BM, as well as levels of GATA-3
      expression in BM ILC2s. Furthermore, the frequency of BM PLZF+ ILC precursors was
      higher in males and increased by excess androgens, suggesting that androgens act
      to inhibit the transition of ILC precursors to ILC2s. Taken together, these data
      show that a functional subset of KLRG1- ILC2s in females contributes to the sex
      bias in lung ILC2s that is observed after reproductive age.

PMID- 29568819
TI  - Sublanguage Corpus Analysis Toolkit: A tool for assessing the representativeness
      and sublanguage characteristics of corpora.
AB  - Sublanguages are varieties of language that form "subsets" of the general
      language, typically exhibiting particular types of lexical, semantic, and other
      restrictions and deviance. SubCAT, the Sublanguage Corpus Analysis Toolkit,
      assesses the representativeness and closure properties of corpora to analyze the
      extent to which they are either sublanguages, or representative samples of the
      general language. The current version of SubCAT contains scripts and applications
      for assessing lexical closure, morphological closure, sentence type closure, over
      represented words, and syntactic deviance. Its operation is illustrated with
      three case studies concerning scientific journal articles, patents, and clinical
      records. Materials from two language families are analyzed-English (Germanic),
      and Bulgarian (Slavic). The software is available at sublanguage.sourceforge.net
      under a liberal Open Source license.

PMID- 29568818
TI  - Developing Robust Predictive Models for Head and Neck Cancer across Microarray
      and RNA-seq Data.
AB  - Increased understanding of the transcriptomic patterns underlying head and neck
      squamous cell carcinoma (HNSCC) can facilitate earlier diagnosis and better
      treatment outcomes. Integrating knowledge from multiple studies is necessary to
      identify fundamental, consistent gene expression signatures that distinguish
      HNSCC patient samples from disease-free samples, and particularly for detecting
      HNSCC at an early pathological stage. This study utilizes feature integration and
      heterogeneous ensemble modeling techniques to develop robust models for
      predicting HNSCC disease status in both microarray and RNAseq datasets. Several
      alternative models demonstrated good performance, with MCC and AUC values
      exceeding 0.8. These models were also applied to discriminate between early
      pathological stage HNSCC and normal RNA-seq samples, showing encouraging results.
      The predictive modeling workflow was integrated into a software tool with a
      graphical user interface. This tool enables HNSCC researchers to harness
      frequently observed transcriptomic features and ensembles of previously developed
      models when investigating new HNSCC gene expression datasets.

PMID- 29568820
TI  - SuperCAT: The (New and Improved) Corpus Analysis Toolkit.
AB  - This paper reports SuperCAT, a corpus analysis toolkit. It is a radical extension
      of SubCAT, the Sublanguage Corpus Analysis Toolkit, from sublanguage analysis to
      corpus analysis in general. The idea behind SuperCAT is that representative
      corpora have no tendency towards closure-that is, they tend towards infinity. In
      contrast, non-representative corpora have a tendency towards closure-roughly,
      finiteness. SuperCAT focuses on general techniques for the quantitative
      description of the characteristics of any corpus (or other language sample),
      particularly concerning the characteristics of lexical distributions.
      Additionally, SuperCAT features a complete re-engineering of the previous SubCAT
      architecture.

PMID- 29568821
TI  - Reproducibility in Natural Language Processing: A Case Study of Two R Libraries
      for Mining PubMed/MEDLINE.
AB  - There is currently a crisis in science related to highly publicized failures to
      reproduce large numbers of published studies. The current work proposes, by way
      of case studies, a methodology for moving the study of reproducibility in
      computational work to a full stage beyond that of earlier work. Specifically, it
      presents a case study in attempting to reproduce the reports of two R libraries
      for doing text mining of the PubMed/MEDLINE repository of scientific
      publications. The main findings are that a rational paradigm for reproduction of
      natural language processing papers can be established; the advertised
      functionality was difficult, but not impossible, to reproduce; and
      reproducibility studies can produce additional insights into the functioning of
      the published system. Additionally, the work on reproducibility lead to the
      production of novel user-centered documentation that has been accessed 260 times
      since its publication-an average of once a day per library.

PMID- 29568822
TI  - Ethical Issues in Corpus Linguistics And Annotation: Pay Per Hit Does Not Affect
      Effective Hourly Rate For Linguistic Resource Development On Amazon Mechanical
      Turk.
AB  - Ethical issues reported with paid crowdsourcing include unfairly low wages. It is
      assumed that such issues are under the control of the task requester. Can one
      control the amount that a worker earns by controlling the amount that one pays?
      412 linguistic data development tasks were submitted to Amazon Mechanical Turk.
      The pay per HIT was manipulated through a range of values. We examined the
      relationship between the pay that is offered per HIT and the effective pay rate.
      There is no such relationship. Paying more per HIT does not cause workers to earn
      more: the higher the pay per HIT, the more time workers spend on them (R = 0.92).
      So, the effective hourly rate stays roughly the same. The finding has clear
      implications for language resource builders who want to behave ethically: other
      means must be found in order to compensate workers fairly. The findings of this
      paper should not be taken as an endorsement of unfairly low pay rates for
      crowdsourcing workers. Rather, the intention is to point out that additional
      measures, such as pre-calculating and communicating to the workers an average
      hourly, rather than per-task, rate must be found in order to ensure an ethical
      rate of pay.

PMID- 29568823
TI  - Graph-Constrained Sparse Construction of Longitudinal Diffusion-Weighted Infant
      Atlases.
AB  - Constructing longitudinal diffusion-weighted atlases of infant brains poses
      additional challenges due to the small brain size and the dynamic changes in the
      early developing brains. In this paper, we introduce a novel framework for
      constructing longitudinally-consistent diffusion-weighted infant atlases with
      improved preservation of structural details and diffusion characteristics. In
      particular, instead of smoothing diffusion signals by simple averaging, our
      approach fuses the diffusion-weighted images in a patch-wise manner using sparse
      representation with a graph constraint that encourages spatiotemporal
      consistency. Diffusion-weighted atlases across time points are jointly
      constructed for patches that are correlated in time and space. Compared with
      existing methods, including the one using sparse representation with l2,1
      regularization, our approach generates longitudinal infant atlases with much
      richer and more consistent features of the developing infant brain, as shown by
      the experimental results.

PMID- 29568824
TI  - Multimodal Hyper-connectivity Networks for MCI Classification.
AB  - Hyper-connectivity network is a network where every edge is connected to more
      than two nodes, and can be naturally denoted using a hyper-graph. Hyper
      connectivity brain network, either based on structural or functional interactions
      among the brain regions, has been used for brain disease diagnosis. However, the
      conventional hyper-connectivity network is constructed solely based on single
      modality data, ignoring potential complementary information conveyed by other
      modalities. The integration of complementary information from multiple modalities
      has been shown to provide a more comprehensive representation about the brain
      disruptions. In this paper, a novel multimodal hyper-network modelling method was
      proposed for improving the diagnostic accuracy of mild cognitive impairment
      (MCI). Specifically, we first constructed a multimodal hyper-connectivity network
      by simultaneously considering information from diffusion tensor imaging and
      resting-state functional magnetic resonance imaging data. We then extracted
      different types of network features from the hyper-connectivity network, and
      further exploited a manifold regularized multi-task feature selection method to
      jointly select the most discriminative features. Our proposed multimodal hyper
      connectivity network demonstrated a better MCI classification performance than
      the conventional single modality based hyper-connectivity networks.

PMID- 29568825
TI  - q-Space Upsampling Using x-q Space Regularization.
AB  - Acquisition time in diffusion MRI increases with the number of diffusion-weighted
      images that need to be acquired. Particularly in clinical settings, scan time is
      limited and only a sparse coverage of the vast q-space is possible. In this
      paper, we show how non-local self-similar information in the x-q space of
      diffusion MRI data can be harnessed for q-space upsampling. More specifically, we
      establish the relationships between signal measurements in x-q space using a
      patch matching mechanism that caters to unstructured data. We then encode these
      relationships in a graph and use it to regularize an inverse problem associated
      with recovering a high q-space resolution dataset from its low-resolution
      counterpart. Experimental results indicate that the high-resolution datasets
      reconstructed using the proposed method exhibit greater quality, both
      quantitatively and qualitatively, than those obtained using conventional methods,
      such as interpolation using spherical radial basis functions (SRBFs).

PMID- 29568826
TI  - Online Statistical Inference for Large-Scale Binary Images.
AB  - We present a unified online statistical framework for quantifying a collection of
      binary images. Since medical image segmentation is often done semi-automatically,
      the resulting binary images may be available in a sequential manner. Further,
      modern medical imaging datasets are too large to fit into a computer's memory.
      Thus, there is a need to develop an iterative analysis framework where the final
      statistical maps are updated sequentially each time a new image is added to the
      analysis. We propose a new algorithm for online statistical inference and apply
      to characterize mandible growth during the first two decades of life.

PMID- 29568827
TI  - A divergent and concise total synthesis of (-)-lycoposerramine R and (+)
      lycopladine A.
AB  - A concise, asymmetric and divergent synthesis of lycoposerramine R and
      lycopladine A is presented. The synthesis features the palladium-catalyzed
      cycloalkenylation of a silyl enol ether for assembling the 5/6-hydrindane system
      and generating a quaternary carbon center in one step.

PMID- 29568828
TI  - Multitude NMR studies of alpha-synuclein familial mutants: probing their
      differential aggregation propensities.
AB  - Familial mutations in alpha-synuclein affect the immediate chemical environment
      of the protein's backbone, changing its aggregation kinetics and forming diverse
      structural and functional intermediates. This study, concerning two oppositely
      aggregating mutants A30P and E46K, reveals a completely diverse conformational
      landscape for each, thus providing atomistic insights into differences in their
      aggregation dynamics.

PMID- 29568829
TI  - Spin-orbit effects in optical spectra of gold-silver trimers.
AB  - Cationic gold-silver trimers are ideal model systems for the evaluation of
      relativistic electronic structure theories. The closed-shell triangles allow one
      to test density functional and wavefunction-based methods in their prediction of
      optical properties, as dependent on composition and symmetry. Here we present the
      gas-phase optical spectra of AgNAu3-N+ (N = 0-3) clusters recorded by
      longitudinal photodissociation spectroscopy in the photon energy range 1.9-4.4
      eV. The experimental data are compared to excited electronic state calculations
      in the framework of all-electron range-separated time-dependent density
      functional and equation-of-motion coupled cluster theory using two-component as
      well as the spin-free scalar relativistic theories. In particular, it is shown
      that for mixed trimers scalar-relativistic corrections are insufficient and a two
      component approach becomes obligatory for a correct description of optical
      response properties including both spin-orbit coupling and charge-transfer
      effects.

PMID- 29568830
TI  - Theoretical aspects in structural distortion and the electronic properties of
      lithium peroxide under high pressure.
AB  - The structural phase transition and electronic properties of Li2O2 under
      pressures up to 500 GPa have been investigated using first-principles
      calculations. Two new structural phase transitions have been proposed at
      pressures around 75 GPa from the P63/mmc structure to the P21 structure and
      around 136 GPa from the P21 structure to the P21/c structure. The calculated
      phonon spectra have confirmed the dynamical stability of these structures. The
      pressure dependence of the lattice dynamics, O-O bond length, and band gaps in
      Li2O2 have also been reported. The band gaps of the P63/mmc, P21, and P21/c
      structures calculated by PBE and HSE06 have shown increasing trends with
      increasing pressure. Interestingly, the P63/mmc band gap and c/a ratio have
      significantly decreased with the increasing O-O bond length and ELF value around
      11 and 40 GPa. At these pressures, the phonon frequency of the O-O stretching
      modes has softened. This finding reveals the effects of structural distortion in
      three phases of Li2O2. Our study provides structural understanding and the
      electronic properties of Li2O2 under high pressure, which might be useful for
      investigating the charge transport through Li2O2 in lithium-air batteries and CO2
      capture.

PMID- 29568831
TI  - Designing a porous-crystalline structure of beta-Ga2O3: a potential approach to
      tune its opto-electronic properties.
AB  - beta-Ga2O3 has drawn recent attention as a state-of-the-art electronic material
      due to its stability, optical transparency and appealing performance in power
      devices. However, it has also found a wider range of opto-electronic applications
      including photocatalysis, especially in its porous form. For such applications, a
      lower band gap must be obtained and an electron-hole spatial separation would be
      beneficial. Like many other metal oxides (e.g. Al2O3), Ga2O3 can also form
      various types of porous structure. In the present study, we investigate how its
      optical and electronic properties can be changed in a particular porous structure
      with stoichiometrically balanced and extended vacancy channels. We apply a set of
      first principles computational methods to investigate the formation and the
      structural, dynamic, and opto-electronic properties. We find that such an
      extended vacancy channel is mechanically stable and has relatively low formation
      energy. We also find that this results in a spatial separation of the electron
      and hole, forming a long-lived charge transfer state that has desirable
      characteristics for a photocatalyst. In addition, the electronic band gap reduces
      to the vis-region unlike the transparency in the pure beta-Ga2O3 crystal. Thus,
      our systematic study is promising for the application of such a porous structure
      of beta-Ga2O3 as a versatile electronic material.

PMID- 29568832
TI  - Neutral and cationic cyclic (alkyl)(amino)carbene mercury [cAAC-Hg(ii)]
      complexes: scope of hydroamination of alkynes with organomercury compounds.
AB  - This study demonstrates the first synthesis of cyclic (alkyl)(amino)carbene
      (cAAC) adducts of Hg(ii), [cAACMe.HgBr(MU-Br)]2 (1a) and [cAACcy.HgBr(MU-Br)]2
      (1b). Adduct 1b catalyzes intermolecular hydroamination of aromatic alkynes and
      amines under mild conditions to afford aromatic imines. The quest to prepare an
      electrophilic Hg(ii) complex resulted in the synthesis of cationic
      [(cAACcy)2Hg(H2O)]2+2[NO3]- (3) by reacting 1b with AgNO3.

PMID- 29568833
TI  - Prediction of optimal structural water concentration for maximized performance in
      tunnel manganese oxide electrodes.
AB  - Crystal water has been shown to stabilize next-generation energy storage
      electrodes with structural tunnels to accommodate cation intercalation, but the
      stabilization mechanism is poorly understood. In this study, we present a simple
      physical model to explain the energetics of interactions between the electrode
      crystal lattice, structural water, and electrochemically cycled ions. Our model
      is applied to understand the effects of crystal water on sodium ion intercalation
      in a tunnel manganese oxide structure, and we predict that precisely controlling
      the crystal water concentration can optimize the ion intercalation voltage and
      capacity and promote stable cycling. The analysis yields a critical structural
      water concentration by accounting for the interplay between elastic and
      electrostatic contributions to the free energy. Our predictions are validated
      with first-principles calculations and electrochemical measurements. The
      theoretical framework used here can be extended to predict critical
      concentrations of stabilizing molecules to optimize performance in next
      generation battery materials.

PMID- 29568834
TI  - Measurement of the mechanical properties of single Synechocystis sp. strain
      PCC6803 cells in different osmotic concentrations using a robot-integrated
      microfluidic chip.
AB  - Synechocystis sp. strain PCC6803 (Synechocystis) is a model microorganism and its
      mechanosensitive (MS) channels play important roles in its osmoadaptation
      mechanism. When the osmotic concentration of the culture environment changes, the
      inner pressure of the cell also changes due to the transportation of water
      through ion channels. Because the tension in the cell membrane relates to the
      inner pressure, we expect that the response of the MS channels to an osmotic
      concentration change could be evaluated by measuring their mechanical properties.
      Here, we propose a system for the measurement of the mechanical properties of a
      single Synechocystis cell. We developed a robot-integrated microfluidic chip
      combined with optical tweezers. The chip has an external actuated pushing probe
      and a force sensor probe. A single cell was located between the tip of both
      probes using the optical tweezers and was then deformed using the probes. As a
      result, we could measure the force and deformation and compare the Young's moduli
      of two groups: a group of wild type cells and a group of mutant (genetically
      modified) cells with a defect in the MS channels, at three different osmotic
      concentrations. The results showed that the Young's modulus of each group changed
      according to the osmotic concentration, while changes in cell size were too small
      to be detected. These results confirmed that the proposed evaluation method
      provides an understanding of the physiological function of MS channels for
      keeping the cell integrity of microorganisms when the cells are exposed to
      different external osmotic changes.

PMID- 29568835
TI  - Construction of beta to carbonyl stereogenic centres by asymmetric 1,4-addition
      of alkylzirconocenes to dienones and ynenones.
AB  - Copper-catalyzed asymmetric 1,4-addition of alkylzirconium species to linear
      alpha,beta,gamma,delta unsaturated dienones and ynenones is reported. A variety
      of alkyl nucleophiles are introduced with good yields and excellent regio- and
      enantio-selectivities to give tertiary carbon centres bearing multiple functional
      groups. The method is also applicable to an ynethioate with ee's over 96%.

PMID- 29568837
TI  - An ammonia-based etchant for attaining copper nanoclusters with green
      fluorescence emission.
AB  - Luminescent copper nanoclusters (CuNCs) constitute a very active research topic
      due to their unique properties and lower cost than gold and silver NCs. In this
      study, we report a new, facile, and rapid top-down etching method for
      synthesizing luminescent CuNCs, using Cu nanoparticles (CuNPs) as the precursor
      and ammonia (NH3) as the etchant. The etching mechanism is systematically
      investigated and the optical and structural properties of the obtained CuNCs are
      carefully studied. The NH3-triggered etching process is very fast and the newly
      generated CuNCs can emit strong green fluorescence with a high quantum yield.
      Moreover, by coupling the urease-catalyzed hydrolysis of urea with the NH3
      induced etching of CuNPs, we developed a novel fluorescence turn-on assay for
      urea. The linear range for urea detection is from 0.25 to 5 mM, and the limit of
      detection is 0.01 mM. This novel sensing approach, with good sensitivity and
      excellent selectivity, is then successfully utilized to detect urea in human
      serum samples, demonstrating its great potential in clinical diagnosis. In
      addition, the proposed coupling method can be extended to monitor other analytes
      that influence the size-focusing etching process, allowing metal NCs to be used
      to construct diverse chemosensors and biosensors.

PMID- 29568838
TI  - A unifying view of the broad-spectrum antiviral activity of RSAD2 (viperin) based
      on its radical-SAM chemistry.
AB  - RSAD2 (cig-5), also known as viperin (virus inhibitory protein, endoplasmic
      reticulum associated, interferon inducible), is a member of the radical S
      adenosylmethionine (SAM) superfamily of enzymes. Since the discovery of this
      enzyme more than a decade ago, numerous studies have shown that it exhibits
      antiviral activity against a wide range of viruses. However, there is no clear
      picture demonstrating the mechanism by which RSAD2 restricts the replication
      process of different viruses, largely because there is no direct evidence
      describing its in vivo enzymatic activity. As a result, a multifunctionality
      model has emerged. According to this model the mechanism by which RSAD2 restricts
      replication of different viruses varies and in many cases is not dependent on the
      radical-SAM chemistry of RSAD2. If the radical-SAM activity of RSAD2 is not
      required for its antiviral function, the question worth asking is: why does the
      cellular defence mechanism induce the expression of the radical-SAM enzyme RSAD2,
      which is metabolically expensive due to the requirement for a [4Fe-4S] cluster
      and usage of SAM? Here, in contrast to the multifunctionality view, I put forward
      a unifying model. I postulate that the radical-SAM activity of RSAD2 modulates
      cellular metabolic pathways essential for viral replication and/or cell
      proliferation and survival. As a result, its catalytic activity restricts the
      replication of a wide range of viruses via a common cellular function. This view
      is based on recent discoveries hinting towards possible substrates of RSAD2, re
      evaluation of previous studies regarding the antiviral activity of RSAD2, and
      accumulating evidence suggesting a role of human RSAD2 in the metabolic
      reprogramming of cells.

PMID- 29568839
TI  - Potassium fluoride activation for the nucleophilic fluorination reaction using 18
      crown-6, [2.2.2]-cryptand, pentaethylene glycol and comparison with the new hydro
      crown scaffold: a theoretical analysis.
AB  - Activation of potassium fluoride salt for selective and fast nucleophilic
      fluorination requires its solubilization and stabilization of the respective
      transition state. This goal can be achieved through control of the nano
      environment around the reactants via cation or ion-pair binding catalysis. In
      this work, six different species were theoretically investigated as promoters and
      catalysts for nucleophilic fluorination: tri-tert-butanolamine, 18-crown-6,
      pentaethylene glycol, [2.2.2]-cryptand, and two new hydroxylated crown ethers
      (hydro-crowns). Calculations using the PBE functional and the LPNO-CEPA method,
      as well as the SMD continuum model, were carried out for the SN2 reaction of KF
      with ethyl bromide in toluene solution as a model system. The present study
      points out that [2.2.2]-cryptand is the most effective promoter of the reaction
      when using stoichiometric quantities. In the case of a catalytic process, the new
      DB18C6-4OH is the most effective molecule considering only a 1 : 1 complex. The
      hydroxyl groups are important for the solubilization of potassium fluoride and
      for the catalytic cycle. Nevertheless, the DB18C6-4OH hydro-crown can form a 2 :
      2 complex and is needed to add bulk groups close to the hydroxyls to avoid
      dimerization. The calculated overall free energy of activation for reactions
      promoted by 18-crown-6, pentaethylene glycol, and [2.2.2]-cryptand is in good
      agreement with the experimental data.

PMID- 29568840
TI  - Catalytic cyanosilylation using germylene stabilized platinum(ii) dicyanide.
AB  - The ability of a platinum compound to act as a catalyst for the cyanosilylation
      of carbonyl compounds is demonstrated through a well-defined germylene stabilized
      Pt(ii) dicyanide, trans-{(iBu)2ATIGe(iPr)}2Pt(CN)2.

PMID- 29568841
TI  - Factors influencing the decision to pursue emergency medicine as a career among
      medical students in Singapore.
AB  - INTRODUCTION: The introduction of the residency programme in Singapore allows
      medical students to apply for residency in their graduating year. Our study aimed
      to determine the interest levels and motivating factors for pursuing emergency
      medicine (EM) as a career among medical students in Singapore. METHODS: A self
      administered questionnaire was distributed to Year 1-5 medical students in 2012.
      Participants indicated their interest in pursuing EM as a career and the degree
      to which a series of variables influenced their choices. Influencing factors were
      analysed using multinomial logistic regression. RESULTS: A total of 800 completed
      questionnaires were collected. 21.0% of the participants expressed interest in
      pursuing EM. Perceived personality fit and having done an elective in EM were
      strongly positive influencing factors. Junior medical students were more likely
      to cite the wide diversity of medical conditions and the lack of a long-term
      doctor-patient relationship to be negative factors, while senior medical students
      were more likely to cite personality fit and perceived prestige of EM as negative
      factors. CONCLUSION: Careful selection of EM applicants is important to the
      future development of EM in Singapore. Our study showed that personality fit
      might be the most important influencing factor in choosing EM as a career.
      Therefore, greater effort should be made to help medical students explore their
      interest in and suitability for a particular specialty. These include giving
      medical students earlier exposure to EM, encouraging participation in student
      interest groups and using appropriate personality tests for career guidance.

PMID- 29568842
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in
      gastrointestinal cancers: fad or standard of care?
AB  - Peritoneal metastases (PM) are the common endpoint for patients with advanced
      gastrointestinal cancers. PM from these cancers are often managed in a similar
      fashion to other sites of systemic metastases, but the following must be taken
      into consideration. (a) PM do not respond to systemic chemotherapy in the same
      fashion as liver and lung metastases. (b) PM cause local problems, resulting in
      disruption of chemotherapy. (c) Cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy (CRS-HIPEC) actually work for PM. (d) PM are not
      easily detected on imaging modalities. There has been mounting evidence of the
      effectiveness of CRS-HIPEC at prolonging survival in selected patients with
      colorectal and gastric PM, but there remains a reluctance to explore this
      treatment modality. This is likely because of the perceived morbidity and
      mortality. An effective management strategy employing CRS-HIPEC for selected
      patients with gastrointestinal PM can only be achieved if a concerted effort is
      made to understand this disease and address the concerns regarding this
      treatment.

PMID- 29568843
TI  - Emeritus Professor Chia Boon Lock (1939-2017): Doyen of cardiology.

PMID- 29568836
TI  - Ratiometric optical nanoprobes enable accurate molecular detection and imaging.
AB  - Exploring and understanding biological and pathological changes are of great
      significance for early diagnosis and therapy of diseases. Optical sensing and
      imaging approaches have experienced major progress in this field. Particularly,
      an emergence of various functional optical nanoprobes has provided enhanced
      sensitivity, specificity, targeting ability, as well as multiplexing and
      multimodal capabilities due to improvements in their intrinsic physicochemical
      and optical properties. However, one of the biggest challenges of conventional
      optical nanoprobes is their absolute intensity-dependent signal readout, which
      causes inaccurate sensing and imaging results due to the presence of various
      analyte-independent factors that can cause fluctuations in their absolute signal
      intensity. Ratiometric measurements provide built-in self-calibration for signal
      correction, enabling more sensitive and reliable detection. Optimizing nanoprobe
      designs with ratiometric strategies can surmount many of the limitations
      encountered by traditional optical nanoprobes. This review first elaborates upon
      existing optical nanoprobes that exploit ratiometric measurements for improved
      sensing and imaging, including fluorescence, surface enhanced Raman scattering
      (SERS), and photoacoustic nanoprobes. Next, a thorough discussion is provided on
      design strategies for these nanoprobes, and their potential biomedical
      applications for targeting specific biomolecule populations (e.g. cancer
      biomarkers and small molecules with physiological relevance), for imaging the
      tumor microenvironment (e.g. pH, reactive oxygen species, hypoxia, enzyme and
      metal ions), as well as for intraoperative image guidance of tumor-resection
      procedures.

PMID- 29568844
TI  - Cytomegalovirus (CMV) hepatitis: an uncommon complication of CMV reactivation in
      drug reaction with eosinophilia and systemic symptoms.

PMID- 29568845
TI  - Authors' reply.

PMID- 29568846
TI  - Authors' reply.

PMID- 29568847
TI  - Haematologist-reviewed peripheral blood smear in paediatric practice.
AB  - Manual examination of the peripheral blood smear (PBS) is currently performed on
      a fraction of samples sent for automated complete cell count. 39 children (age
      range 0-16.2 years) referred to a private paediatric practice during a 16-month
      period were retrospectively reviewed. Clinical scenarios, haematological
      features, laboratory-initiated PBS review, haematologist's PBS review and final
      diagnosis were described. Clinical indications included isolated thrombocytopenia
      (n = 10), unexplained bruises (n = 5), acute febrile illnesses (n = 11), anaemia
      (n = 8) and others (n = 5). The laboratory reviewed the PBS in 30 cases according
      to preset criteria and made no conclusive remarks. All slides were reviewed by a
      haematologist and a diagnosis was made in 27 (69%) cases, including 7 (78%) of
      the nine slides the laboratory did not review. The practice of laboratory
      initiated PBS review requires re-evaluation. Haematologist-reviewed PBS is an
      important diagnostic tool for children with anaemia, bleeding disorders and acute
      febrile illnesses.

PMID- 29568848
TI  - Clinics in diagnostic imaging (184). Fat embolism syndrome (FES).
AB  - A 23-year-old Indian man presented with shortness of breath and new-onset
      confusion along with a rash on his chest on Postoperative Day 2, following
      internal fixation of his femur fracture. Although computed tomography pulmonary
      angiography was negative for filling defects in the pulmonary vasculature, it
      showed mosaic attenuation changes with some interlobular septal thickening.
      Magnetic resonance imaging of the brain showed patchy signal abnormalities,
      predominantly in the grey-white matter junction region with extensive
      susceptibility artefacts, consistent with petechial haemorrhages. The laboratory
      work-up showed thrombocytopenia and anaemia. A diagnosis of fat embolism syndrome
      was established, based on the clinical presentation combined with laboratory and
      imaging findings. The clinical and imaging features of fat embolism syndrome are
      discussed.

PMID- 29568849
TI  - Intravascular large B-cell lymphoma presenting as panniculitis clinically: a case
      report.

PMID- 29568851
TI  - Comment on: Empathy and burnout: a study on residents from a Singapore
      institution.

PMID- 29568850
TI  - Medication-related osteonecrosis of the jaw in osteoporotic patients: prevention
      and management.
AB  - Osteoporosis is a major, growing healthcare issue. This is especially of concern
      in an ageing population like that of Singapore. Osteoporotic patients are at risk
      of fractures, which can result in increased morbidity and mortality. The use of
      antiresorptive therapy with bisphosphonates or denosumab has been proven to
      reduce fracture risk. However, the use of these medications has rarely been
      associated with the development of osteonecrosis of the jaw, a potentially
      debilitating condition affecting one or both jaws. Appropriate understanding of
      the patient's antiresorptive therapy regime, as well as early institution of
      preventive dental measures, can play an important role in preventing medication
      related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral
      to specialist care is warranted for patients with established MRONJ.

PMID- 29568852
TI  - Ministry of Health Clinical Practice Guidelines: Chronic Obstructive Pulmonary
      Disease.
AB  - The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on
      Chronic Obstructive Pulmonary Disease (COPD) to provide doctors and patients in
      Singapore with evidence-based treatment for COPD. This article reproduces the
      introduction and executive summary (with recommendations from the guidelines)
      from the MOH Clinical Practice Guidelines on COPD, for the information of SMJ
      readers. Chapters and page numbers mentioned in the reproduced extract refer to
      the full text of the guidelines, which are available from the Ministry of Health
      website:
      https://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelin
      s/cpg_medical.html. The recommendations should be used with reference to the full
      text of the guidelines. Following this article are multiple choice questions
      based on the full text of the guidelines.

PMID- 29568853
TI  - Popliteal artery entrapment syndrome in a Singaporean mixed martial arts fighter.

PMID- 29568854
TI  - Comment on: Definitive tests for dengue fever: when and which should I use?

PMID- 29568855
TI  - Prevailing practices in airway management: a prospective single-centre
      observational study of endotracheal intubation.
AB  - INTRODUCTION: Airway management during anaesthesia has potential difficulties and
      risks. We aimed to investigate the utility of routine airway assessment for
      predicting difficult tracheal intubation, review the prevailing practice of
      videolaryngoscope use amongst anaesthetists in a teaching hospital and determine
      the incidence of intraoperative and postoperative airway-related complications.
      METHODS: A prospective observational study of 1,654 patients undergoing general
      anaesthesia with endotracheal intubation over a seven-month period was performed.
      Data regarding airway and anaesthetic management was collected and analysed.
      RESULTS: Videolaryngoscopes were used as the first-choice equipment in 60.5% of
      the cohort. The incidence of difficult intubation was 2.1%, of which 45.7% of
      cases were unanticipated. The sensitivity of airway assessment was 54.3%, with a
      positive predictive value of 8.1%. When difficult intubation was anticipated,
      more videolaryngoscopes were used as the first equipment of choice compared to
      the Macintosh laryngoscope (p < 0.001). In the Macintosh group, more patients
      required a change of airway equipment (p = 0.015), but the number of intubation
      attempts was similar (p = 0.293). The incidence of intraoperative (p = 0.920) and
      postoperative complications (p = 0.380) were similar in both groups. CONCLUSION:
      Using the current predictors of difficult intubation, half of the difficult
      airways we encountered were unanticipated. Videolaryngoscopes were preferred when
      difficulty was anticipated and were also used in routine tracheal intubation.

PMID- 29568856
TI  - Approach to the forgetful patient.
AB  - Singapore has an ageing population with a projected 53,000 people aged >= 60
      years living with dementia by 2020. Primary care doctors have the opportunity to
      initiate early work-up for reversible causes of cognitive dysfunction, allowing
      identification of comorbidities and discussion of medical therapy options. Early
      diagnosis confers the sick role on the patient, which allays frustration and
      explains events and behaviour that may have strained relationships with family
      and friends. The patient can be encouraged to plan for future health and personal
      care options with a Lasting Power of Attorney and/or Advance Care Planning.
      Objective cognitive tests (e.g. abbreviated mental test and Mini-Mental State
      Examination) and brain imaging are adjuncts that help in formulating the
      diagnosis. Referral to a hospital memory clinic activates a multidisciplinary
      team approach to dementia, including clinical consultation, dementia counselling,
      physiotherapy sessions on gait/fall prevention, occupational therapy sessions on
      cognitive stimulation and caregiver training.

PMID- 29568857
TI  - Accelerated inflammation and oxidative stress induced by LPS in acute lung
      injury: Iotanhibition by ST1926.
AB  - Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl
      retinoid ST1926, have been well developed and investigated in clinical trials for
      many diseases. The aim of our study was to explore the role of ST1926 in
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to reveal the
      possible molecular mechanism. Mice were treated with LPS to induce acute lung
      injury followed by ST1926 administration. After LPS induction, mice administered
      with ST1926 showed lower inflammation infiltration in bronchoalveolar lavage
      (BAL) fluid, and pro-inflammatory cytokines, including interleukin-1beta (IL
      1beta), IL-18, IL-6 and tumor necrosis factor-alpha (TNF-alpha) in serum and lung
      tissue samples obtained from mice. In addition, western blot assays suggested
      that ST1926 suppressed nuclear factor-kappaB (NF-kappaB), inhibitor-kappaB kinase
      alpha (IkappaBalpha) and IkappaB kinase (IKKalpha), as well as Toll-like receptor
      4 (TLR4) induced by LPS. In addition, reactive oxygen species (ROS) stimulated by
      LPS was also suppressed for ST1926 through inhibiting p38 and extracellular
      receptor kinase (ERK) signaling pathway. Taken together, the data here indicated
      that ST1926 may be of potential value in treating acute lung injury through
      inflammation and ROS suppression via inactivating TLR4/NF-kappaB and p38/ERK1/2
      signaling pathways.

PMID- 29568858
TI  - Cardioprotective effect of rosuvastatin against isoproterenol-induced myocardial
      infarction injury in rats.
AB  - Rosuvastatin, a member of 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors, exerts various pharmacological activities. This study evaluated the
      cardioprotective effect of rosuvastatin on isoproterenol-induced myocardial
      infarction injury in rats. A rat model of myocardial infarction injury was
      induced by isoproterenol (ISO) for 2 consecutive days, rosuvastatin was
      administered for 8 weeks. The levels of myocardial infarct size, aspartate
      transaminase (AST), alanine transaminase (ALT), creatine kinase-MB (CK-MB),
      lactate dehydrogenase (LDH) activities, as well as malondialdehyde (MDA) levels,
      superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT)
      activities and reduced glutathione (GSH) concentrations were determined.
      Hematoxylin and eosin staining was used to observe cardiac histological changes.
      Interleukin-1beta (IL-1beta) and IL-18 levels in heart tissues were detected with
      ELISA kits. The mRNA and protein levels of NOD-like receptor superfamily, pyrin
      domain containing 3 (NLRP3) inflammasome were measured by qRT-PCR and western
      blot analysis, respectively. Our results showed that treatment with rosuvastatin
      reduced myocardial infract area, ameliorated histopathological alterations in
      myocardium, and decreased activities of myocardial injury marker enzymes in ISO
      induced rats. In addition, rosuvastatin remarkably restored ISO-induced elevation
      of lipid peroxidation and decrease of antioxidants, significantly reduced
      myocardial pro-inflammatory cytokines concentrations in this animal model.
      Furthermore, rosuvastatin significantly inhibited the activation of NLRP3
      inflammasome in this animal model. This study demonstrates that rosuvastatin
      significantly alleviates ISO-induced myocardial infarction injury. The mechanism
      is associated with attenuation of oxidative stress and inflammation, via the
      inhibition of NLRP3 inflammasome.

PMID- 29568859
TI  - Effects of three-dimensional collagen scaffolds on the expression profiles and
      biological functions of glioma cells.
AB  - Three-dimensional (3D) culture has been increasingly used to investigate tumor
      cell biology for improved simulation of the natural developing environment.
      However, the way in which 3D culture affects the gene expression and biological
      functions of glioma cells remains to be fully elucidated. In the present study,
      3D culture environments were established using collagen scaffolds with different
      pore sizes, followed by the comparison of gene expression profiles and associated
      biological functions of glioma cells, including the U87, U251 and HS683 cell
      lines, in 3D collagen scaffolds with conventional two-dimensional (2D) cultured
      cells. Finally, the possible signaling pathways regulating these differences were
      investigated. It was found that the 3D collagen scaffold culture upregulated the
      expression of genes associated with stemness, cell cycle, apoptosis, epithelia
      mesenchymal transition, migration, invasion and glioma malignancy, and induced
      the corresponding functional changes. Apoptotic pathways, the Wnt pathway, Sonic
      Hedgehog pathway and Notch pathway, may be involved in the regulation of these
      changes. The aperture size of the collagen-scaffold did not appear to affect the
      gene expression or functions of the glioma cells. The results of the study
      suggested that the 3D collagen scaffold enhanced the malignancy of glioma cells
      and may be a promising in vitro platform for investigations of glioma.

PMID- 29568860
TI  - Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and
      induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway.
AB  - Esculin is a derivative of coumarin, which is also an active ingredient of ash
      bark, and has antibacterial, anti-inflammatory, anti-allergy and skin protective
      effects. The underlying mechanism and protective effects of esculin on cognitive
      impairment in experimental diabetic nephropathy (DN) was investigated in the
      present study. Male C57BL/6J 6-week-old mice were injected intravenously with a
      single dose of streptozotocin (STZ; 30 mg/kg). At 2 weeks after the STZ
      injection, mice received intravenous injection with 5, 10 or 20 mg/kg esculin for
      2 weeks. In the present study, the results of the Morris water maze test
      demonstrated that esculin significantly improved behavior and recognition memory
      in STZ-induced diabetic rats. Furthermore, treatment of STZ-induced diabetic rats
      with esculin significantly inhibited tumor necrosis factor-alpha, interleukin-6,
      malondialdehyde, monocyte chemoattractant protein-1 and intracellular adhesion
      molecule-1 activity levels, and increased the activity of superoxide dismutase,
      in the kidney, which was determined by ELISA. In addition, esculin treatment
      significantly suppressed the renal protein expression of activator protein 1,
      phosphorylated (p)-p38 mitogen activated protein kinase (MAPK) and p-c-Jun N
      terminal kinase, and increased p-extracellular signal regulated kinase 1/2
      protein expression, in STZ-induced diabetic rats, as determined by western
      blotting. These results indicate that esculin may ameliorate cognitive impairment
      in experimental DN, and exert anti-oxidative stress and anti-inflammatory
      effects, via the MAPK signaling pathway. Thus, it may serve as a potential target
      for cognitive impairment of DN in the future.

PMID- 29568861
TI  - Neuroprotective effects of salidroside administration in a mouse model of
      Alzheimer's disease.
AB  - Salidroside administration improves memory in different models of learning.
      However, its influence on models of Alzheimer's disease (AD) has not been widely
      studied. In the present study, the therapeutic effect of salidroside was
      investigated in an animal model of AD. APPswe/PS1DeltaE9 mouse (n=20) were
      randomly divided into either the AD model group or the salidroside + AD model
      group (n=10 in each group), and C57BL/6J mouse (n=20) of identical age and
      genetic background were randomly divided into either the normal control (NC)
      group or the salidroside + NC group (n=10 in each group). The Morris water maze
      behavioral test was applied to all mice in order to investigate the effects of
      salidroside administration on learning and memory functions. The concentrations
      of malondialdehyde (MDA), glutathione (GSH) and nitrate in the hippocampus of the
      mice were determined, and hippocampal superoxide dismutase (SOD) activity was
      also determined. In addition, terminal deoxynucleotidyl-transferase-mediated dUTP
      nick end labeling was used to investigate the rate of neuronal apoptosis in the
      hippocampus. Furthermore, the concentrations of interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were tested for in the brain tissues of AD
      mice. Learning and memory functions in AD mice were revealed to improve following
      administration of salidroside. Furthermore, salidroside administration was
      revealed to decrease the concentrations of MDA and nitrate in the hippocampus,
      decrease the apoptotic rate of hippocampal neurons, and increase the activity of
      SOD and the concentration of GSH in hippocampal tissue. In addition, it was
      demonstrated that salidroside administration suppressed the expression levels of
      IL-6 and TNF-alpha. In conclusion, this study revealed that the administration of
      salidroside could attenuate the effects of AD-associated memory and learning
      impairment in mice. Furthermore, it was demonstrated that the effects of
      salidroside administration on AD mice were, at least partially, via inhibition of
      brain oxidative/nitrosative damage, suppression of both IL-6 and TNF-alpha
      expression levels, and suppression of the hippocampal neuronal apoptotic rate.

PMID- 29568862
TI  - Overexpression of appoptosin promotes mitochondrial damage in MIN6 cells.
AB  - Damage to pancreatic beta-cells is closely associated with diabetes. However, the
      mechanism underlying injury to pancreatic beta-cells remains unclear, although
      hypoxia is considered as one of the leading causes. Appoptosin is a mitochondrial
      protein that promotes neuronal apoptosis. Studies conducted on appoptosin thus
      far have primarily focused on Alzheimer's disease, and have demonstrated that the
      expression of appoptosin is significantly increased in ischemic-reperfused rat
      brains, which indicates its close association with hypoxia. However, the role of
      appoptosin in pancreatic beta-cells, which are sensitive to hypoxia, remains
      unknown. Therefore, the current study aimed to investigate the function of
      appoptosin in pancreatic beta-cells in a hypoxic environment. Cobalt chloride
      (CoCl2) was used to mimic the hypoxic status of the cells. The results of a
      terminal deoxynucleotidyl transferase dUTP nick-end labeling assay demonstrated
      that CoCl2 promoted apoptosis in MIN6 mouse insulinoma cells, and western
      blotting and reverse transcription-quantitative polymerase chain reaction results
      demonstrated that the activation of appoptosin was induced, promoting
      mitochondrial damage and caspase 3 activation. Silencing of appoptosin using
      short hairpin RNA significantly reduced CoCl2-induced apoptosis in MIN6 cells. In
      conclusion, CoCl2 increased the expression of appoptosin, which aggravated
      mitochondrial damage in MIN6 cells. Therefore, inhibiting the expression of
      appoptosin may benefit pancreatic beta-cells survival during islet
      transplantation.

PMID- 29568863
TI  - TIPE-2 suppresses growth and aggressiveness of hepatocellular carcinoma cells
      through downregulation of the phosphoinositide 3-kinase/AKT signaling pathway.
AB  - Rapid proliferation and migration are the main features of hepatocellular
      carcinoma (HCC) cells, which serve an essential role in carcinogenesis and are a
      hallmark of cancer therapy resistance. Previous studies have reported that tumor
      necrosis factor-alpha-induced protein-8 like-2 (TIPE-2) is involved in cancer
      initiation and the progression of HCC. The present study aimed to clarify the
      role of TIPE-2 in HCC carcinogenesis, growth and aggressiveness. The effects of
      TIPE-2 on HCC were determined using colony forming and cell cycle analyses. Cell
      apoptosis, and growth and aggressiveness of HCC cells, were investigated
      following TIPE-2 treatment. Treatment with TIPE-2 markedly suppressed HCC cell
      proliferation and increased the number of cells in S phase of the cell cycle. The
      results demonstrated that TIPE-2 significantly inhibited growth, migration and
      invasion of HCC cells via the downregulation of tumor metastasis-associated
      genes. Flow cytometric analysis indicated that TIPE-2 promoted apoptosis of HCC
      cells via regulation of apoptosis-associated gene transcription. In addition,
      TIPE-2 administration downregulated the expression of phosphoinositide 3-kinase
      (PI3K) and protein kinase B (AKT) in HCC cells. In addition, TIPE-2 selectively
      decreased neuroblastoma Ras viral oncogene and p27 expression in HCC cells. In
      vivo assays revealed that TIPE-2 significantly inhibited tumor growth and
      prolonged animal survival by promoting apoptosis of tumor cells. The results of
      the present study indicated that TIPE-2 acts as an inhibitor of HCC cell growth
      and aggressiveness, and promotes apoptosis, thus suggesting that TIPE-2 may
      inhibit the metastasis-associated PI3K/AKT signaling cascade and may arrest the
      tumor cell cycle. These findings provide a potential molecular mechanism by which
      TIPE-2 promotes apoptosis of HCC cells.

PMID- 29568864
TI  - Protective effect of curcumin against ultraviolet A irradiation-induced
      photoaging in human dermal fibroblasts.
AB  - Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory
      processes in skin, resulting in photoaging. Natural botanicals have gained
      considerable attention due to their beneficial protection against the harmful
      effects of UV irradiation. The present study aimed to evaluate the ability of
      curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A
      (UVA)-induced photoaging. HDFs were treated with 0-10 uM Cur for 2 h and
      subsequently exposed to various intensities of UVA irradiation. The cell
      viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry
      assays, respectively. The effect of UVA and Cur on the formation of reactive
      oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and
      the levels/activity of antioxidative defense proteins, including glutathione,
      superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin
      diacetate and commercial assay kits. Furthermore, western blotting was performed
      to determine the levels of proteins associated with endoplasmic reticulum (ER)
      stress, the apoptotic pathway, inflammation and the collagen synthesis pathway.
      The results demonstrated that Cur reduced the accumulation of ROS and restored
      the activity of antioxidant defense enzymes, indicating that Cur minimized the
      damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis
      demonstrated that Cur may attenuate UVA-induced ER stress, inflammation and
      apoptotic signaling by downregulating the protein expression of glucose-regulated
      protein 78, C/EBP-homologous protein, nuclear factor-kappaB and cleaved caspase
      3, while upregulating the expression of Bcl-2. Additionally, it was demonstrated
      that Cur may regulate collagen metabolism by decreasing the protein expression of
      matrix metalloproteinase (MMP)-1 and MMP-3, and may promote the repair of cells
      damaged as a result of UVA irradiation through increasing the protein expression
      of transforming growth factor-beta (TGF-beta) and Smad2/3, and decreasing the
      expression of the TGF-beta inhibitor, Smad7. In conclusion, the results of the
      present study indicate the potential benefits of Cur for the protection of HDFs
      against UVA-induced photoaging and highlight the potential for the application of
      Cur in skin photoprotection.

PMID- 29568865
TI  - Trifluoperazine induces apoptosis through the upregulation of Bax/Bcl-2 and
      downregulated phosphorylation of AKT in mesangial cells and improves renal
      function in lupus nephritis mice.
AB  - The inhibition of mesangial cell (MC) proliferation has become an important
      therapy in preventing glomerular proliferation diseases. Trifluoperazine (TFP)
      has been reported to inhibit the proliferation of several types of cancer cell,
      however, the effects of TFP in renal proliferation diseases remain to be fully
      elucidated. The present study examined the effects of TFP on the proliferation of
      MCs and quantified cell apoptosis progression in vivo and in vitro. The effects
      of various TFP concentrations and treatment durations on cell proliferation and
      cell apoptosis in vitro were analyzed using flow cytometry in conjunction with a
      Cell Counting kit-8 assay. Cell proliferation in vivo was determined using
      hematoxylin and eosin staining and immunohistochemistry of Ki67. The expression
      of the two cell apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bcl-2
      associated X protein (Bax), were estimated using western blot analysis and
      immunohistochemistry in vivo and in vitro. TFP-induced phosphatidylinositol 3
      kinase (PI3K)/protein kinase B (AKT) signaling pathways were also estimated using
      western blot analysis. These results suggested that TFP inhibited MC
      proliferation in a dose- and time-dependent manner. It was found that TFP
      inhibited the abnormal proliferation of MCs, which was stimulated by 20% fetal
      bovine serum in vitro and in lupus MRL/lpr mice. TFP promoted cell apoptosis,
      downregulated the expression of Bcl-2 and upregulated the expression of Bax in a
      dose-dependent manner at mRNA and protein levels. In addition, TFP inhibited
      phosphorylated AKT, potentially leading to the suppressed activation of PI3K/AKT
      signaling pathways. TFP treatment significantly decreased the levels of blood
      urea nitrogen and serum creatinine, but had no significant effects on the body
      weight and liver function of the lupus mice. These results validated and
      reinforced the potential of TFP in the treatment of mesangial proliferative
      diseases.

PMID- 29568866
TI  - Incorporation of CD40 ligand enhances the immunogenicity of tumor-associated
      calcium signal transducer 2 virus-like particles against lung cancer.
AB  - The cell surface glycoprotein Trop-2 is overexpressed in various types of cancer,
      including in lung cancer, and has recently been used as an effective
      immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor
      superfamily member, is a promising immune adjuvant. Human immunodeficiency virus
      (HIV) gag-based virus-like particles (VLPs) are highly immunogenic, and foreign
      antigens can be incorporated onto their membrane envelope for cancer vaccine
      development. In the present study, a HIV gag-based VLP strategy and Bac-to-Bac
      system were utilized to construct Trop-2, CD40L and gag recombinant
      baculoviruses, which were then used to infect TN5 cells in order to form Trop-2
      VLPs or Trop-2-CD40L VLPs. These VLPs were characterized using transmission
      electron microscopy and western blot analysis methods. VLPs incorporating murine
      Trop-2 only or incorporating Trop-2 and CD40L were used to immunize C57BL/6 mice.
      Immunized mice demonstrated high humoral and cellular immunity responses, whereas
      the Trop-2-CD40L VLPs led to higher immune responses in comparison with Trop-2
      only VLPs. Immunization with Trop-2-CD40L VLPs also reduced tumor growth more
      effectively compared with Trop-2 VLPs. Furthermore, Trop-2-CD40L VLP immunization
      increased the survival rate of Lewis tumor-bearing mice more significantly when
      compared with Trop-2 only VLPs. In conclusion, the present study provided a novel
      vaccine design by combination of a tumor antigen and an immune adjuvant based on
      a VLP strategy, which may be potentially applied as an alternative
      immunotherapeutic option in the treatment of lung cancer.

PMID- 29568867
TI  - miR-503 suppresses the proliferation and metastasis of esophageal squamous cell
      carcinoma by triggering autophagy via PKA/mTOR signaling.
AB  - MicroRNA (miR)-503 is involved in the regulation of the malignant phenotype in
      multiple tumor types, and has been proven to be a novel diagnostic and
      therapeutic target; however, its function and mechanisms of action have not yet
      been fully elucidated in esophageal squamous cell carcinoma (ESCC). In the
      current study, we detected miR-503 expression by RT-qPCR and found that miR-503
      expression was increased in ESCC, but negatively correlated with lymph node
      metastasis, TNM stage and tumor differentiation. Functionally, we confirmed that
      miR-503 inhibited the proliferation and metastasis of ESCC cells by triggering
      cellular autophagy. Mechanistically, we confirmed that miR-503 exerted its
      biological effects by targeting protein kinase CAMP-activated catalytic subunit
      alpha (PRKACA) in ESCC by dual luciferase reporter assay. Moreover, miR-503 was
      found to trigger autophagy in ESCC cells through the protein kinase A
      (PKA)/mammalian target of rapamycin (mTOR) pathway. Taken together, our results
      demonstrate that miR-503 suppresses the proliferation and metastasis of ESCC via
      the activation of autophagy, mediated by the PKA/mTOR signaling pathway.

PMID- 29568868
TI  - Polo-like kinase 2 promotes chemoresistance and predicts limited survival benefit
      from adjuvant chemotherapy in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common malignances worldwide.
      Chemoresistance remains a major issue in the field of CRC treatment. The present
      study aimed to investigate the potential role of polo-like kinase 2 (Plk2) in
      chemoresistance in CRC. The associations between Plk2 and clinicopathological
      factors, as well as chemotherapeutic benefit were analyzed with a publicly
      available CRC dataset. The correlation between Plk2 expression and
      chemosensitivity was further confirmed in CRC cells. Moreover, knockdown and
      exogenous overexpression experiments of Plk2 were carried out to uncover the
      potential role of Plk2 in regulating the chemoresistance of CRC cells. We found
      that the expression of Plk2 was significantly associated with proximally located
      tumors. In addition, it was found that high expression ofPlk2 was associated with
      deficient mismatch repair status, B-raf serine/threonine kinase proto-oncogeneand
      Kirsten rat sarcoma viral oncogene homolog mutations. By contrast, tumor protein
      53 mutation was correlated with a low expression level of Plk2. A higher
      expression level of Plk2 significantly predicted a poorer outcome in patients
      with CRC. However, the prognostic significance was only observed in patients who
      received adjuvant chemotherapy. In CRC cells, higher levels of Plk2 were
      associated with increased resistance to chemotherapeutic agents. Knocking down
      the expression of Plk2 resulted in elevated cellular apoptosis induced by
      oxaliplatin. By contrast, exogenous overexpression of Plk2 exerted an anti
      apoptotic effect and enhanced the resistance of CRC cells to chemotherapeutic
      agents. In conclusion, a high expression of Plk2 was associated with
      chemoresistant traits of CRC through inhibiting apoptosis. These results
      suggested that Plk2 may serve as a predictive marker for chemoresistance and a
      novel target in CRC treatment.

PMID- 29568869
TI  - Therapeutic effects of liver soothing pingchuan formula decoction on experimental
      asthma in BALB/c mice via regulation of nerve growth factor-tyrosine kinase A
      pathway.
AB  - The present study was designed to investigate the effects of liver soothing
      pingchuan formula decoction (LSPF) on experimental asthma in BALB/c mice and
      explore its potential molecular mechanisms. An animal model of asthma was
      established in BALB/c mice through sensitization and activation with
      intraperitoneal injection of 10% ovalbumin (OVA)/Al(OH)3 solution in addition to
      inhalation of a 5% OVA solution. LSPF (300 and 600 mg/kg/day) was initially
      administered orally prior to activation. Following this, bronchoalveolar lavage
      fluid (BALF) and lung tissues were collected for histopathalogical examination.
      Levels of inflammatory cells and cytokines were determined in the BALF, and
      levels of nerve growth factor (NGF) and tyrosine kinase A (TrkA) in the lung
      tissues were determined. The results of the present study indicated that
      increased inflammatory reactions were observed following OVA sensitization
      (P<0.05), and the expression levels of NGF (P<0.05) and TrkA (P<0.05) were
      significantly increased, compared with normal mice. Notably, compared with the
      asthma model group, immunohistochemical results revealed that LSPF treatment
      suppressed OVA induced inflammatory reactions (P<0.05) and NGF (P<0.05) and TrkA
      expression levels (P<0.05). In addition, the NGF (P<0.05) and TrkA (P<0.05) were
      revealed to be downregulated with LSPF treatment from the results of the ELISA
      and western blotting assay. Overall, the results of the present study
      demonstrated that LSPF exhibits therapeutic effects on experimental asthma in
      mice, via downregulation of the NGF-TrkA pathway.

PMID- 29568870
TI  - MicroRNA-599 targets high-mobility group AT-hook 2 to inhibit cell proliferation
      and invasion in clear cell renal carcinoma.
AB  - Dysregulation of microRNAs (miRNAs) is associated with the occurrence and
      development of clear cell renal cell carcinoma (ccRCC) through their
      participation in a number of critical biological processes. Therefore, an in
      depth investigation into miRNAs and their biological roles within ccRCC may
      provide useful insights and lead to the identification of novel therapeutic
      methods for patients with ccRCC. miRNA-599 (miR-599) serves critical roles in
      different types of human cancer. However, the expression pattern, biological
      function and molecular mechanism of miR-599 in ccRCC remain unknown. The present
      study aimed to detect the expression level of miR-599 in ccRCC, examine its
      effect on ccRCC progression and further explore the possible underlying
      mechanisms. It was observed that miR-599 was significantly underexpressed in
      ccRCC tissues and cell lines compared with the control. Functional assays
      revealed that restored expression of miR-599 restricted the proliferation and
      invasion of ccRCC cells. Bioinformatics analysis, luciferase reporter assay,
      reverse transcription-quantitative polymerase chain reaction and western blot
      analysis demonstrated that high-mobility group AT-hook 2 (HMGA2) was a direct
      target of miR-599 in ccRCC. HMGA2 knockdown simulated the suppressive effects
      caused by miR-599 overexpression in ccRCC. Recovered HMGA2 expression partially
      rescued the miR-599-mediated inhibition of ccRCC proliferation and invasion.
      These results suggest that miR-599 may serve tumour suppressive roles in ccRCC by
      directly targeting HMGA2, indicating that miR-599 may have potential as a
      treatment for patients with ccRCC.

PMID- 29568871
TI  - Involvement of multidrug resistance protein 4 in the hepatocyte efflux of
      lamivudine and entecavir.
AB  - Multidrug resistance protein 4 (MRP4) is capable of transporting acyclic
      nucleotide phosphonates, but little is known about its role in lamivudine (LAM)
      and entecavir (ETV) transport. In the present study, the involvement of MRP4 in
      the transport of LAM and ETV was investigated through in vitro experiments. The
      cytotoxicity of three antiviral drugs and their activities against HBV as
      characterized in HepG2.4D14 [wild-type hepatitis B virus (HBV)] and HepG2.A64
      (ETV-resistant HBV) cells. LAM, ETV and tenofovir (TFV) demonstrated a 50%
      effective concentration against HBV of 4.14+/-0.03, 0.13+/-0.02 and 3.24+/-0.01
      uM in HepG2.4D14 cells and of 5.94+/-0.20, 6.28+/-0.07 and 11.43+/-0.09 uM in
      HepG2.A64 cells, respectively. After administering 3-([(3-(2-[7-chloro-2
      quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoporphyl)-thio)-methyl]-thio)
      propanoic acid (MK571), the intracellular concentrations of all three drugs were
      much lower than the extracellular drug concentrations in these two cell types,
      whereas the intracellular drug concentrations in wild-type cells were higher than
      those in ETV-resistant cells. Furthermore, the intracellular levels of LAM, ETV
      and TFV were enhanced and the extracellular concentrations were reduced by
      addition of MK571. Thus, MRP4 is mainly responsible for the efflux of LAM and ETV
      in hepatocyte cultures. These results may contribute to enhancing antiviral
      efficacy.

PMID- 29568872
TI  - IL-10 inhibits retinal pigment epithelium cell proliferation and migration
      through regulation of VEGF in rhegmatogenous retinal detachment.
AB  - Rhegmatogenous retinal detachment (RRD) is a disorder of the eye that affects
      physical and mental health. Retinal pigment epithelium (RPE) is closely
      associated with RRD, and it is hypothesized that RPE-secreted inflammatory
      cytokines may induce early pathological changes of RRD and may participate in RPE
      proliferation and migration. The present study determined a role for interleukin
      (IL)-10 as an RPE-secreted immune regulatory factor that contributes to RRD. A
      rat RRD model was established and RPE cells were isolated and cultivated. RPE
      cells were randomly divided into four groups, three treated with different
      concentrations of IL-10 (100, 50, and 20 mM) and one untreated. RPE cell
      proliferation was evaluated by MTT assay and the activity of caspase-3 was also
      measured. RPE cell invasion was determined by Transwell assay. Vascular
      endothelial growth factor A (VEGF) expression was examined by reverse
      transcription-quantitative polymerase chain reaction and western blotting; IL-1
      and IL-6 levels were measured by ELISA. IL-10 treatment suppressed RPE cell
      proliferation and migration, promoted caspase-3 activity, inhibited VEGF mRNA and
      protein expression, and downregulated the secretion of inflammatory cytokines IL
      1 and IL-6 in RRD group compared with the untreated Model group. The
      aforementioned effects of IL-10 became more evident with increasing IL-10
      concentration. IL-10 suppressed inflammation, facilitated RPE cell apoptosis and
      inhibited cell proliferation and migration through the regulation of VEGF
      expression.

PMID- 29568873
TI  - The deficiency of CX3CL1/CX3CR1 system ameliorates high fructose diet-induced
      kidney injury by regulating NF-kappaB pathways in CX3CR1-knock out mice.
AB  - Fructose, the most important functional food additive from the last century, has
      been widely used in industry, agriculture, light industry, food and medicine.
      With the improvement of people's living standard and economic level, excess
      intake of fructose results in metabolic symptoms, including hyperleptinemia,
      insulin resistance and neuroinflammation is causing high risk of chronic kidney
      disease development in humans and animals. However, the underlying molecular
      mechanism of renal injury is still not fully understood, and the development of
      effective drugs and treatments are delayed. Hence, we investigated the role of
      crosstalk of CX3CL1-CX3CR1 axis and nuclear factor-kappaB (NF-kappaB) signaling
      pathway in the development of renal injury. CX3CL1-knock-out C57BL/6 mice were
      constructed and used to analyze the influence of CX3CL1-related signaling
      pathways on kidney injury of wild-type (WT) mice and CXECR1 deficiency mice,
      which were administrated with 30% fructose water. Western blotting, quantitative
      RT-PCR (qRT-PCR), immunohistochemistry, ELISA, flow cytometry and biochemical
      indicator analysis were used to determine the levels of renal injury and key
      signaling pathway associated with renal damage. The results indicated that
      administration of high fructose intake can cause typical renal inflammatory
      responses in serum and tissues. Fructose enhances the CX3CL1-CX3CR1 axis and NF
      kappaB activation, and promotes crosstalk of CX3CL1-CX3CR1 and NF-kappaB
      pathways. The phosphorylated AKT could be significantly activated in fructose
      induced renal injury via CX3CL1-CX3CR1 axis. CX3CR1 expression between WT and
      CX3CR1-/- mice were evaluated to establish their relationship with injury. Our
      results indicated that CX3CR1 may be the central and major indicator in the
      process of renal injury, which mediate AKT pathway and further enhance the NF
      kappaB activation. These findings demonstrated that crosstalk of CX3CL1-CX3CR1
      axis and NF-kappaB signaling pathway play a direct role in fructose-induced
      kidney injury. Inhibition of CX3CL1-CX3CR1 pathway may suppress renal-related
      diseases. It may be a potential treatment choice for the clinical diagnoses and
      treatment in the future.

PMID- 29568874
TI  - Silencing of ASPP2 promotes the proliferation, migration and invasion of triple
      negative breast cancer cells via the PI3K/AKT pathway.
AB  - Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via
      binding with p53 and then enhancing the transcriptional activities toward pro
      apoptosis genes. ASPP2 has recently been reported to serve a major role in p53
      independent pathways. Triple-negative breast cancer (TNBC) is a type of breast
      cancer that is more aggressive and highly lethal when p53 is mutated. In the
      present study, the mRNA level of ASPP2 was found to be suppressed in breast
      tumors compared with that in adjacent normal breast tissues, and the expression
      of ASPP2 was also decreased in a series of breast cancer cell lines compared with
      that in MCF-10A normal breast cells. Downregulation of ASPP2 by specific small
      interfering RNA (siRNA) transfection was able to promote cell growth, reduce cell
      apoptosis, and contribute to cell migration and invasion. Furthermore,
      downregulation of ASPP2 promoted cell epithelial-mesenchymal transition (EMT) in
      MDA-MB-231 and HCC-1937 TNBC cells. Furthermore, it was found that when ASPP2
      siRNA was transfected into MDA-MB-231 and HCC-1937 cells, the expression of
      phosphoinositide-3-kinase regulatory subunit 1 (p85alpha) decreased and
      phosphorylation of protein kinase B (AKT) increased, which are key molecular
      regulators in the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In
      conclusion, the present data indicated that ASPP2 had a crucial influence on the
      proliferation and metastasis in TNBC, and that the functional mechanism may be
      p53-independent to a great extent. ASPP2 and its link with the PI3K/AKT pathway
      deserve further investigation and may provide novel insights into therapeutic
      targets for TNBC.

PMID- 29568875
TI  - Expression of Rv2031c-Rv2626c fusion protein in Mycobacterium smegmatis enhances
      bacillary survival and modulates innate immunity in macrophages.
AB  - Dormancy-associated antigens encoded by the dormancy survival regulon (DosR)
      genes are required for survival of Mycobacterium tuberculosis (Mtb) in
      macrophages. However, mechanisms underlying survival of Mtb in macrophages
      remains to be elucidated. A recombinant Mycobacterium smegmatis strain (rMs)
      expressing a fusion protein of two dormancy-associated antigens Rv2031c and
      Rv2626c from Mtb was constructed in the present study. In an in vitro culture,
      growth rate of rMs was lower compared with Ms. A total of 24 h following
      infection of murine macrophages with rMs or Ms, percentage of viable cells
      decreased and the number of bacteria in viable cells increased compared with Ms,
      demonstrating that virulence and intracellular survival of rMs were enhanced.
      Compared with macrophages infected with Ms, necrosis of macrophages infected with
      rMs was increased, while apoptosis was inhibited. Macrophages infected with rMs
      secreted more interferon-gamma and interleukin-6, but fewer nitric oxide and
      tumor necrosis factor-alpha, compared with macrophages infected with Ms. The
      present study demonstrated that the fusion protein composed of dormancy
      associated antigens Rv2031c and Rv2626c in Ms serves a physiological function of
      a dormancy-associated antigen and modulates innate immunity of host macrophages,
      therefore favoring intracellular bacillary survival.

PMID- 29568876
TI  - Fisetin administration improves LPS-induced acute otitis media in mouse in vivo.
AB  - Acute otitis media is one of the most common infectious diseases worldwide in
      spite of the widespread vaccination. The present study was conducted to explore
      the effects of fisetin on mouse acute otitis media models. The animal models were
      established by lipopolysaccharide (LPS) injection into the middle ear of mice via
      the tympanic membrane. Fisetin was administered to mice for ten days through
      intragastric administration immediate after LPS application. Hematoxylin and
      eosin (H&E) staining was performed and the pro-inflammatory cytokines, including
      interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6 and
      VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and
      RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB)
      signaling pathway was detected by immunoblotting assays. Reactive oxygen species
      (ROS) generated levels were determined through assessment of anti-oxidants, and
      TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular
      mechanism for acute otitis media progression and the function of fisetin. Fisetin
      reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro
      inflammatory cytokine release was downregulated accompanied with TLR4/NF-kappaB
      inactivation. ROS production was significantly decreased in comparison to the LPS
      treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin
      treatment in LPS-induced mice with acute otitis media. The above results
      indicated that fisetin improved acute otitis media through inflammation and ROS
      suppression via inactivating TLR4/NF-kappaB and TXNIP/MAPKs signaling pathways.

PMID- 29568877
TI  - MicroRNA-22 inhibits the proliferation and migration, and increases the cisplatin
      sensitivity, of osteosarcoma cells.
AB  - Osteosarcoma (OS) is the major type of primary bone tumor and is associated with
      a poor prognosis due to chemotherapy resistance. Accumulating evidence indicates
      that microRNAs (miRNAs/miRs) may influence the tumor progression of OS and cell
      sensitivity to chemotherapy. In the present study, a total of 7 patients with OS
      and 7 healthy volunteers were recruited. Reverse transcription-quantitative
      polymerase chain reaction and ELISA were performed to determine the expression of
      miRNAs and mRNAs in the serum of participants. Furthermore, the biological
      function of miR-22 and S100A11 was examined in MG-63 cells using Cell Counting
      Kit-8 assays, Transwell migration assays and western blot analysis to determine
      the effects on cell proliferation, migration and protein expression,
      respectively, while MG-63 cell sensitivity to cisplatin was assessed by measuring
      cell viability following cisplatin treatment and calculating the half maximal
      inhibitory concentration (IC50). Additionally, the association between miR-22 and
      S100 calcium-binding protein A11 (S100A11) was validated using a luciferase
      reporter assay. The results demonstrated that miR-22 expression was significantly
      reduced in patients with OS and the MG-63 OS cell line, compared with healthy
      volunteers and the normal osteoblast hFOB 1.19 cell line, respectively, while the
      expression of S100A11 was negatively associated with miR-22 levels in the MG-63
      cell line. Furthermore, overexpression of miR-22 inhibited the proliferation and
      migratory ability of MG-63 cells, and increased the sensitivity of MG-63 cells to
      cisplatin treatment; however, overexpression of S100A11 partially attenuated the
      alterations in proliferation, migratory ability and chemosensitivity that were
      induced by miR-22 overexpression. In addition, it was confirmed that S100A11 is a
      direct target gene of miR-22 in MG-63 cells. In conclusion, to the best of our
      knowledge, the present study is the first to demonstrate that miR-22 may be a
      promising therapeutic target and may have potential as part of a combination
      treatment alongside chemotherapeutic agents for OS.

PMID- 29568878
TI  - Hypoxia induces endothelial-mesenchymal transition in pulmonary vascular
      remodeling.
AB  - It is well established that hypoxia induces epithelial-mesenchymal transition in
      vitro and in vivo. However, the role of hypoxia in endothelial-mesenchymal
      transition (EndMT), an important process in the pathogenesis of pulmonary
      hypertension, is not well-characterized. The present study demonstrated a
      significant downregulation of the endothelial marker CD31 and its co-localization
      with a mesenchymal marker, alpha-smooth muscle actin (alpha-SMA), in the intimal
      layer of small pulmonary arteries of rats exposed to chronic hypoxia. These
      results suggest a possible role of hypoxia in inducing EndMT in vivo. Consistent
      with these observations, pulmonary microvascular endothelial cells (PMVECs)
      cultured under hypoxic conditions exhibited a significant decrease in CD31
      expression, alongside a marked increase in the expression of alpha-SMA and two
      other mesenchymal markers, collagen (Col) 1A1 and Col3A1. In addition, hypoxia
      promoted the proliferation and migration of alpha-SMA-expressing mesenchymal-like
      cells, but not of PMVECs. Of note, knockdown of hypoxia-inducible factor 1alpha
      (HIF-1alpha) effectively inhibited hypoxic induction of alpha-SMA, Col1A1 and the
      transcription factor Twist1, while rescuing hypoxic suppression of CD31; these
      results suggest that HIF-1alpha is essential for hypoxia-induced EndMT and that
      it serves as an upstream regulator of Twist1. Mechanistically, HIF-1alpha was
      identified to bind to the promoter of the Twist1 gene, thus activating Twist1
      transcription and regulating EndMT. Collectively, the present results indicate
      that the HIF-1alpha/Twist1 pathway has a critical role in mediating the effect of
      hypoxia-induced EndMT in pulmonary arterial remodeling.

PMID- 29568879
TI  - Retinal ganglion cell-conditioned medium and surrounding pressure alters gene
      expression and differentiation of rat retinal progenitor cells.
AB  - Loss of retinal ganglion cells is implicated in glaucoma and high intraocular
      pressure. Factors that affect the differentiation of retinal progenitor cells
      into retinal ganglion cells remain unclear. The present study aimed to
      investigate the effects of retinal ganglion cell-conditioned medium on gene
      expression and differentiation in retinal progenitor cells, and the effects of
      surrounding pressure on the survival and differentiation of retinal progenitor
      cells. Retinal progenitor cells and retinal ganglion cells were isolated from
      rats. Immunofluorescence staining of Nestin and Thy1 was performed to identify
      rat retinal progenitor cells and retinal ganglion cells, respectively. Retinal
      progenitor cells and ganglion cells were cultured for 48 h under surrounding
      pressure of 0, 20, 40, 60 and 80 mmHg. Cellular apoptosis was detected using a
      caspase-3 assay kit. In addition, the culture supernatant of rat retinal ganglion
      cells was collected. Retinal progenitor cells were cultured in the presence or
      absence of retinal ganglion-conditioned medium for 72 h under normal pressure.
      Gene expression of Nestin, paired box protein 6 (PAX6), Thy1 and brain-specific
      homeobox/POU domain protein 3 (Brn-3) in retinal progenitor cells was detected by
      reverse transcription-quantitative polymerase chain reaction. Retinal progenitor
      cells were cultured in retinal ganglion-conditioned medium for 72 h under
      surrounding pressure of 0 and 40 mmHg, respectively, and flow cytometry was
      utilized to evaluate the effects of pressure on the differentiation of retinal
      progenitor cells into retinal ganglion cells. The results demonstrated that
      isolated retinal progenitor cells were Nestin-positive and retinal ganglion cells
      were Thy1-positive, suggesting successful isolation. The activity of caspase-3
      increased in retinal progenitor cells and retinal ganglion cells in a pressure
      dependent manner. When the surrounding pressure reached 40, 60 and 80 mmHg, the
      activity of caspase-3 in retinal progenitor cells and ganglion cells increased
      significantly compared with cells that were not under pressure. Compared with
      retinal progenitor cells cultured without ganglion-conditioned medium, those
      cultured with ganglion-conditioned medium had significantly decreased expression
      levels of Nestin and PAX6, and increased expression levels of Thy1 and Brn3.
      Compared with 0 mmHg pressure, retinal progenitor cells cultured in ganglion
      conditioned medium under 40 mmHg pressure had increased percentages of Thy1
      positive cells. In conclusion, the apoptosis of rat retinal progenitor cells and
      retinal ganglion cells was pressure-dependent. Retinal ganglion cell-conditioned
      medium increased the differentiation of retinal progenitor cells into retinal
      ganglion-like cells, and the differentiation increased as surrounding pressure
      increased. Current study provides insights that may contribute to the efforts of
      developing a treatment for glaucoma.

PMID- 29568880
TI  - Simvastatin induces apoptosis in PTEN-haploinsufficient lipoma cells.
AB  - Adipose tissue tumors (lipomas) frequently develop in patients with heterozygous
      germ line phosphatase and tensin homolog (PTEN) mutations. simvastatin has been
      demonstrated to exhibit antitumor effects, and so the aim of the present study
      was to assess the effects of simvastatin on the growth of human PTEN
      haploinsufficient lipoma cells. Whether the effects of simvastatin in lipomas are
      mediated via PTEN upregulation was also assessed. The results of the present
      study revealed that simvastatin treatment reduced cell viability and induced
      apoptosis in human lipoma cells. Furthermore, it was demonstrated that the
      expression of cellular PTEN mRNA and protein was increased following simvastatin
      stimulation. In addition, the phosphorylation of protein kinase B and downstream
      targets of mammalian target of rapamycin and 4E-binding protein (4E-BP)-1 was
      attenuated. It was also demonstrated that simvastatin induced PTEN
      transcriptional upregulation by increasing peroxisome proliferator-activated
      receptor (PPAR)gamma expression. The small interfering RNA-mediated knockdown of
      PPARgamma abrogated the stimulatory effect of simvastatin on the PTEN protein,
      but did not influence apoptosis. The results of the present study suggest that
      simvastatin may be beneficial for patients with inoperable PTEN haploinsufficient
      lipomas.

PMID- 29568881
TI  - Liraglutide improves hepatic insulin resistance via the canonical Wnt signaling
      pathway.
AB  - Liraglutide, a modified form of glucagon-like peptide-1 (GLP-1), is used in the
      treatment of diabetes mellitus. However, the underlying mechanism by which
      liraglutide improves liver insulin resistance remains to be elucidated. The proto
      oncogene Wnt (Wnt) signaling pathway has been reported to be associated with
      glucose and lipid metabolism. Using in vivo and in vitro models of diabetes and
      insulin resistance, it was investigated whether the beneficial effects of
      liraglutide on liver glucose metabolism are mediated by the Wnt signaling
      pathway. The results of the present study demonstrate that body weight, fasting
      blood glucose, insulin levels and the homeostasis model assessment for insulin
      resistance were markedly decreased in db/db mice treated with liraglutide
      compared with control mice. Liraglutide also improved liver morphology and
      reduced the accumulation of lipid droplets. Furthermore, the expression of
      glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was downregulated,
      whereas the expression of phosphorylated forkhead box O1, Wnt signaling pathway
      associated molecules, beta-catenin, transcription factor 7-like 2 and
      phosphorylated glycogen synthase kinase-3beta was upregulated in the liver of
      mice treated with liraglutide. In the in vitro study, increased gluconeogenesis
      and decreased glucose uptake rates were observed in insulin resistant
      hepatocytes; treatment with liraglutide significantly reversed this effect.
      Furthermore, transfection of insulin resistant hepatocytes with beta-catenin
      small interfering RNA attenuated the effects of liraglutide, suggesting that
      liraglutide improves insulin resistance via activating the beta-catenin/Wnt
      signaling pathway. The results of the present study suggest a novel mechanism
      underlying liraglutide-mediated improvements in insulin resistance in the liver.
      The Wnt signaling pathway may be a potential therapeutic target for the treatment
      of altered hepatic physiology in insulin resistance.

PMID- 29568882
TI  - Long non-coding RNAs RP5-821D11.7, APCDD1L-AS1 and RP11-277P12.9 were associated
      with the prognosis of lung squamous cell carcinoma.
AB  - Lung squamous cell carcinoma (LUSC), a type of non-small cell lung carcinoma, has
      a poor therapeutic response, high relapse rate and poor prognosis. The present
      study was designed to reveal the key long non-coding RNAs (lncRNAs) associated
      with the prognosis of LUSC. The lncRNA expression profiles of LUSC and adjacent
      samples were downloaded from The Cancer Genome Atlas database. Based on the edgeR
      and DEseq packages, the differentially expressed lncRNAs (DELs) between LUSC and
      adjacent samples were obtained and the intersecting DELs were regarded as
      significant DELs. Subsequently, a prognostic risk model was established using Cox
      regression analysis and its classification effect was detected by survival
      analysis. Using survival analysis, the effect of the prognostic risk model was
      assessed in the validation set and other types of cancer. Finally, the co
      expression genes of key lncRNAs were screened using the Multi-Experiment Matrix
      tool and the STRING database, and their functions were predicted via enrichment
      analysis using the Database for Annotation, Visualization and Integrated
      Discovery tool. A total of 2,041 significant DELs between LUSC and adjacent
      samples were screened. The prognostic risk model consisting of RP5-821D11.7,
      APCDD1L-AS1 and RP11-277P12.9 was established, which had a good classification
      effect. Cox multivariate regression analysis demonstrated that risk score may
      serve as an independent prognostic factor. Furthermore, certain co-expression
      genes of RP5-821D11.7 (including proliferating cell nuclear antigen), APCDD1L-AS1
      (including semaphorin 5A, semaphorin 6D, ADAMTS like 1, ADAM metallopeptidase
      with thrombospondin type 1 motif 6, slit guidance ligand 3, and tenascin C) and
      RP11-277P12.9 (including Wnt family member 2B) were identified. Additionally,
      'positive regulation of cell migration' and 'proteinaceous extracellular matrix'
      were enriched. In conclusion, the expression levels of the lncRNAs RP5-821D11.7,
      APCDD1L-AS1 and RP11-277P12.9 may affect the prognosis of LUSC.

PMID- 29568884
TI  - Silencing of aquaporin 5 inhibits the growth of A549 lung cancer cells in vitro
      and in vivo.
AB  - The water channel protein aquaporin 5 (AQP5) is highly expressed in numerous
      tumors. However, its expression pattern and functions in lung cancer in humans
      remain unknown. In the present study, the role of AQP5 in the development of lung
      malignancies was examined. A short hairpin RNA construct targeting AQP5 mRNA was
      transfected into A549 cells to generate a lung cancer cell line in which AQP5
      expression was stably silenced. In vitro and in vivo experiments were then
      performed to establish the effects of AQP5 on A549 cell apoptosis, proliferation
      and cell cycle progression. The results demonstrated that AQP5 silencing
      significantly inhibited the proliferation and promoted the apoptosis of A549 lung
      cancer cells in vitro and in vivo. In addition, it resulted in decreased
      activation of the extracellular signal-regulated kinase 1/2 signaling pathway in
      A549 cells, and reduced levels of the downstream proteins c-Fos and
      phosphorylated cAMP response element-binding protein. Furthermore, inhibition of
      AQP5 expression effectively reduced the tumorigenicity of A549 cells in vivo. In
      conclusion, silencing of AQP5 suppressed the growth of A549 cells in vitro and in
      vivo, suggesting that it may serve as a therapeutic target in lung cancer.

PMID- 29568883
TI  - Everolimus inhibits breast cancer cell growth through PI3K/AKT/mTOR signaling
      pathway.
AB  - Breast cancer is one of the most prevalent malignancies and the leading cause of
      cancer-associated mortality in women worldwide and in China. Everolimus
      (C53H83NO14) is an efficient anti-cancer drug for breast cancer which targets
      mammalian target of rapamycin (mTOR). The present study investigated the
      inhibitory effects of everolimus on breast cancer cells and an MCF-7-bearing
      mouse model. The potential mechanism of the everolimus-mediated decrease in
      growth and aggressiveness of breast cancer cells was reported. Results
      demonstrated that everolimus significantly inhibited breast cancer cell growth,
      migration and invasion. It was demonstrated that everolimus induced apoptosis
      through decreasing B cell lymphoma (Bcl)-2 and Bcl-w and increasing caspase-3 and
      caspase-8 expression levels in breast cancer cells. It was observed that
      everolimus decreased phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and
      mTOR expression levels in breast cancer cells. Results additionally demonstrated
      that PI3 K overexpression prevented that everolimus-mediated inhibition of growth
      and aggressiveness in MCF-7 cells. In vivo assays demonstrated that everolimus
      treatment markedly inhibited tumor growth in the MCF-7 bearing mouse model.
      Overall, these data indicate that everolimus inhibits growth and aggressiveness
      of breast cancer cells through the PI3K/AKT/mTOR signaling pathways, suggesting
      the PI3K/AKT/mTOR signaling pathway may act as a therapeutic target for the
      treatment of human cancer.

PMID- 29568885
TI  - Role of leptin and the leptin receptor in the pathogenesis of varicocele-induced
      testicular dysfunction.
AB  - The present study investigated the expression of leptin and its receptor in the
      left testis and hypothalamus of rats with varicocele and clarified their roles in
      the pathogenesis of varicocele-induced testicular dysfunction. A total of 40 male
      rats were divided randomly into four groups. Groups 1 (G1) and 3 (G3) underwent a
      sham operation. Groups 2 (G2) and 4 (G4) underwent operations to form a
      varicocele created by partial ligation of the left renal vein. G1 and G2 rats
      were euthanized 4 weeks after the operation while G3 and G4 rats were euthanized
      at 8 weeks. The expression of leptin and its receptor was analyzed by
      immunohistochemistry. The mRNA levels of leptin, its receptor, kisspeptin (KiSS
      1), G-protein coupled receptor 54 (GPR54), gonadotropin releasing hormone (GnRH),
      luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured by
      reverse transcription-quantitative polymerase chain reaction. Testicular
      spermatogenesis function and gonadal hormone levels were measured. Compared with
      G1 and G3, the expression of leptin and its receptor in rat testis was
      significantly higher in G2 and G4, respectively. Leptin expression was inversely
      associated with the number of sperm in the left epididymis, thickness of the
      seminiferous epithelium and the diameter of seminiferous tubules. The expression
      of leptin receptors in the hypothalamus of G2 and G4 was significantly increased
      compared with that in G1 and G3, respectively. The mRNA levels of KiSS-1, GPR54,
      GnRH, LH and FSH in G2 and G4 were significantly increased compared with that in
      G1 and G3, respectively. Serum testosterone levels in G2 and G4 rats were
      significantly lower than those in G1 and G3 rats, respectively. There was no
      significant difference between the serum levels of FSH, LH and leptin. These
      results suggest that leptin and its receptor may serve significant roles in the
      pathogenesis of varicocele-induced testicular dysfunction.

PMID- 29568886
TI  - [Corrigendum] MicroRNA-137 has a suppressive role in liver cancer via targeting
      EZH2.
AB  - Following the publication of this article, we realize that an error was made with
      the second author's (Yanlei Sun's) address: This should have been written as
      "Department of General Surgery, Cancer Hospital of Linyi, Linyi, Shandong
      276001", not as "Department of General Surgery, Central Hospital of Linyi, Linyi,
      Shandong 276400". Therefore, the author affiliations and addresses in this paper
      should have appeared as follows: SHICHANG CUI1, YANLEI SUN2, YANG LIU3, CHENGBIAO
      LIU1, JINBAO WANG1, GUANG HAO1 and QIDONG SUN1 1Department of General Surgery,
      Central Hospital of Linyi, Linyi, Shandong 276400; 2Department of General
      Surgery, Cancer Hospital of Linyi, Linyi, Shandong 276001; 3Department of
      Obstetrics and Gynecology, Central Hospital of Linyi, Linyi, Shandong 276400,
      P.R. China. The authors regret this error in the affiliation, and apologize for
      any inconvenience caused. [the original article was published in the Molecular
      Medicine Reports 16: 9494-9502, 2017; DOI: 10.3892/mmr.2017.7828].

PMID- 29568887
TI  - Genome-wide analysis of DNA methylation in human peripheral leukocytes identifies
      potential biomarkers of nonalcoholic fatty liver disease.
AB  - The aim of the present study was to uncover the role of leukocytic DNA
      methylation in the evaluation of nonalcoholic fatty liver disease (NAFLD).
      Patients with biopsy-proven NAFLD (n=35) and normal controls (n=30) were
      recruited from Chinese Han population. Their DNA methylation in peripheral
      leukocytes was subjected to genome-wide profiling. The association between
      differential methylation of CpG sites and NAFLD was further investigated on the
      basis of histopathological classification, bioinformatics, and pyrosequencing. A
      panel of 863 differentially methylated CpG sites dominated by global
      hypomethylation, characterized the NAFLD patients. Hypomethylated CpG sites of
      Acyl-CoA synthetase long-chain family member 4 (ACSL4) (cg15536552) and carnitine
      palmitoyltransferase 1C (CPT1C) (cg21604803) associated with the increased risk
      of NAFLD [cg15536552, odds ratio (OR): 11.44, 95% confidence interval (CI): 1.04
      125.37, P=0.046; cg21604803, OR: 6.57, 95% CI: 1.02-42.15, P=0.047] at cut-off
      beta-values of <3.36 (ACSL4 cg15536552) and <3.54 (CPT1C cg21604803),
      respectively, after the adjustment of age, sex, body mass index (BMI) and
      homeostasis model assessment of insulin resistant (HOMA-IR). Their methylation
      levels also served as biomarkers of NAFLD (ACSL4 cg15536552, AUC: 0.80, 95% CI:
      0.62-0.98, P=0.009; CPT1C cg21604803, AUC: 0.78, 95% CI: 0.65-0.91, P=0.001).
      Pathologically, lowered methylation level (beta-values <3.26) of ACSL4
      (cg15536552) conferred susceptibility to nonalcoholic steatohepatitis (NASH).
      Taken together, genome-wide hypomethylation of peripheral leukocytes may
      differentiate NAFLD patients from normal controls. The leukocytic hypomethylated
      ACSL4 (cg15536552) was suggested to be a biomarker for the pathological
      characteristics of NAFLD.

PMID- 29568888
TI  - Effects of Bushen-Yizhi formula on age-related inflammation and oxidative stress
      in senescence-accelerated mice.
AB  - The present study aimed to investigate the possible effects and underlying
      molecular mechanism of Bushen-Yizhi formula (BSYZ), a traditional Chinese
      medicine, on age-related degeneration of brain physiology in senescence
      accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were
      administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze
      and step-down tests demonstrated that BSYZ significantly improved memory
      impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the
      expression levels of peroxisome proliferator-activated receptor-gamma and B-cell
      lymphoma extra-large, and downregulated the expression levels of inflammatory
      mediators, glial fibrillary acidic protein, cyclooxygenase-2, nuclear factor
      kappaB and interleukin-1beta in the brain compared with untreated SAMP8 mice.
      Furthermore, BSYZ reversed disordered superoxide dismutase activity,
      malondialdehyde content and glutathione peroxidase activity, and ameliorated
      apoptosis and histological alterations. The present study indicated that BSYZ may
      attenuate cognitive impairment in SAMP8 mice, and modulate inflammation,
      oxidative stress and neuronal apoptosis. These results suggested that BSYZ may
      have the potential to be further developed into a therapeutic agent for
      protection against age-related neurodegenerative diseases.

PMID- 29568889
TI  - Treatment of experimental autoimmune myasthenia gravis rats with FTY720 and its
      effect on Th1/Th2 cells.
AB  - Myasthenia gravis (MG) is an autoimmune neurological disease that is
      characterized by the expression of anti-acetylcholine receptor (AChR) antibodies.
      The immune response at AChRs of neuromuscular junction is disrupted in patients
      with MG, which manifests as skeletal muscle fatigue and is aggravated following
      periods of activity and alleviated following rest. Although a novel immune
      suppressant FTY720 drug, which exhibits strong immune suppression efficacy and
      minor adverse effects, is available, its role and mechanism in MG have not been
      elucidated. The aim of this study was to investigate the role of FTY720 in MG. A
      total of 60 healthy female Lewis rats were randomly assigned into 4 groups:
      Control group, Model group of experimental autoimmune myasthenia gravis (EAMG),
      0.5 mg/kg FTY720-treatment EAMG group and 1.0 mg/kg FTY720-treatment EAMG group.
      Body weight and symptoms were examined; Lennon score was used to evaluate
      improvement of clinical symptoms. Reverse transcription-quantitative polymerase
      chain reaction and ELISA were used to test the mRNA and protein expression
      levels, respectively, of the helper T (Th)1 and Th2 cell cytokines, including
      interleukin (IL)-2, interferon (IFN)-gamma, IL-4 and IL-6 in thymus tissue and
      serum. FTY720 treatment improved rat MG symptoms, increased body weight and
      decreased Lennon score. FTY720 treatments also reduced tissue and serum levels of
      IL-2, IFN-gamma and IL-6, but not IL-4 expression levels. FTY720 suppressed the
      inflammatory response and improved EAMG symptoms by inhibiting the secretion of
      inflammatory factors.

PMID- 29568890
TI  - miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in
      gastric cancer cells.
AB  - Despite the improvement in gastric cancer (GC) treatment, multidrug resistance
      (MDR) is still a significant reason for chemotherapy failure. Our previous
      studies have demonstrated that miR-19a/b upregulation directly promoted MDR in GC
      cells. However, the exact regulation and the potential molecule mechanisms have
      not been fully clarified. In this study, we found that miR-19a/b was directly
      involved in 5-aza-2'-deoxycytidine (5-Aza-dC) induced MDR of GC cells.
      Mechanically, demethylation of miR-19a/b repressed methyl CpG binding protein 2
      (MeCP2) expression via direct binding at the 3'-untranslated regions, which then
      alleviated the inhibitory effects of MeCP2 on miR-19a/b expression. Thus, the
      mutual regulatory network sustains preservation of the expression levels of miR
      19a/b. We further demonstrated that miR-19a/b expression was inversely correlated
      to MeCP2 expression in GC tissues. These data showed an intimate interplay among
      miR-19a/b methylation, MeCP2 activity, and MDR, revealing a potential therapeutic
      target for GC.

PMID- 29568891
TI  - Tissue expression of Toll-like receptors 2, 3, 4 and 7 in swine in response to
      the Shimen strain of classical swine fever virus.
AB  - The Toll-like receptors (TLRs) of the innate immune system provide the host with
      the ability to detect and respond to viral infections. The present study aimed to
      investigate the mRNA and protein expression levels of TLR2, 3, 4 and 7 in porcine
      tissues upon infection with the highly virulent Shimen strain of classical swine
      fever virus (CSFV). Reverse transcription-quantitative polymerase chain reaction
      was used to detect the mRNA expression levels of CSFV and TLR, whereas western
      blotting was used to detect the expression levels of TLR proteins. In addition,
      tissues underwent histological examination and immunohistochemistry to reveal the
      histopathological alterations associated with highly virulent CSFV infection and
      to detect TLR antigens. Furthermore, porcine monocyte-derived macrophages (pMDMs)
      were prestimulated with peptidoglycan from Staphylococcus aureus (PGN-SA),
      polyinosinic-polycytidylic acid [poly (I:C)], lipopolysaccharide from Escherichia
      coli 055:B5 (LPS-B5) or imiquimod (R837) in order to analyze the association
      between TLR expression and CSFV replication. Following stimulation for 12 h (with
      TLR-specific ligands), cells were infected with CSFV Shimen strain. The results
      revealed that the expression levels of TLR2 and TLR4 were increased in the lung
      and kidney, but were decreased in the spleen and lymph nodes in response to CSFV.
      TLR3 was strongly expressed in the heart and slightly upregulated in the spleen
      in response to CSFV Shimen strain infection, and TLR7 was increased in all
      examined tissues in the presence of CSFV. Furthermore, R837 and LPS-B5 exerted
      inhibitory effects on CSFV replication in pMDMs, whereas PGN-SA and poly(I:C) had
      no significant effect. These findings highlight the potential role of TLR
      expression in the context of CSFV infection.

PMID- 29568892
TI  - Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI
      rats.
AB  - Microglia, which comprise a sensor for pathological events in the central nervous
      system, may be triggered by nerve injury and transformed from a quiescent state
      into an activated state; ionised calcium binding adaptor molecule 1 (Iba1) is a
      sensitive marker associated with activated microglia. Accumulated evidence
      suggests that spinal activated microglia and the brain-derived neurotrophic
      factor (BDNF)-tyrosine kinase receptor B (TrkB) signalling pathway play major
      roles in the production and development of neuropathic pain. Electro-acupuncture
      (EA) has a positive effect on relieving chronic neuropathic pain; however, the
      underlying mechanisms remain unclear. To determine the significance of EA in the
      treatment of neuropathic pain mediated by activated microglia and the BDNF-TrkB
      signalling pathway in the spinal cord, the mechanical withdrawal threshold (MWT)
      and thermal withdrawal latency (TWL) values were recorded to assess hyperalgesia
      and allodynia. In addition, the amount of activated microglia and BDNF were
      assessed via immunofluorescence. Iba1, BDNF and TrkB mRNA expression levels were
      examined using qPCR; the protein levels of BDNF, p-TrkB and TrkB in the spinal
      cord were analysed via western blotting. The present study demonstrated that EA
      treatment increased the MWT and TWL values. EA significantly inhibited the
      proportion of activated microglia and BDNF expression in the spinal cord after
      chronic constrictive injury (CCI). Furthermore, EA decreased the expression of
      BDNF and TrkB at both the mRNA and protein levels in the spinal cord of CCI rats.
      These findings suggest that the analgesic effect of EA may be achieved by
      inhibiting the activation of spinal microglia and subsequently blocking the BDNF
      TrkB signalling pathway.

PMID- 29568893
TI  - KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in
      CCI rats.
AB  - Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial
      role during chronic neuropathic pain (NP). Following the emergence of NP, gamma
      aminobutyric acid (GABA) A receptor-mediated signaling may be further impaired by
      the changes of KCC2 chloride anion gradient. In the present study, the authors
      investigate the effect of electro-acupuncture (EA) on the behavior and the
      expression of KCC2 and GABAA receptor gamma2 subunit in the spinal cord of
      chronic constriction injury (CCI) model rats. A total of 60 adult male Sprague
      Dawley rats were divided into four groups: Normal group, sham-CCI group, CCI
      group and CCI+EA group. The effect of EA was assessed via the values of
      mechanical withdrawal threshold and thermal withdrawal latency, which were
      significantly improved upon stimulation of the ST-36 and GB-34 acupoints. In
      addition, a marked reduction in both the mRNA and protein levels of KCC2 and
      GABAA receptor gamma2 subunit was observed in the spinal cord following loose
      ligation of the sciatic nerve. The reductions in KCC2 and GABAA receptor gamma2
      subunit expression were reversed by EA treatment. These results support the
      notion that KCC2 and GABAA receptor gamma2 subunit contribute to NP following
      peripheral nerve injury and extend the understanding of the analgesic effects of
      EA on NP.

PMID- 29568894
TI  - Overexpression of satellite alpha transcripts leads to chromosomal instability
      via segregation errors at specific chromosomes.
AB  - The impairment of the stability of the chromosomal structure facilitates the
      abnormal segregation of chromosomes, thus increasing the risk of carcinogenesis.
      Chromosomal stability during segregation is managed by appropriate methylation at
      the centromere of chromosomes. Insufficient methylation, or hypomethylation,
      results in chromosomal instability. The centromere consists of satellite alpha
      repetitive sequences, which are ideal targets for DNA hypomethylation, resulting
      in the overexpression of satellite alpha transcript (SAT). The overexpression of
      SAT has been reported to induce the abnormal segregation of chromosomes. In this
      study, we verified the oncogenic pathway via chromosomal instability involving
      DNA hypomethylation and the overexpression of SAT. For this purpose, we
      constructed lentiviral vectors expressing SAT and control viruses and then
      infected human mammary epithelial cells with these vectors. The copy number
      alterations and segregation errors of chromosomes were evaluated by microarray
      based comparative genomic hybridization (array CGH) and immunocytochemistry,
      respectively. The levels of hypomethylation of satellite alpha sequences were
      determined by MethyLight polymerase chain reaction. Clinical specimens from 45
      patients with breast cancer were recruited to verify the data in vitro. The
      results of immunocytochemistry revealed that the incidence of segregation errors
      was significantly higher in the cells overexpressing SAT than in the controls. An
      array CGH identified the specific chromosomes of 8q and 20q as frequent sites of
      copy number alterations in cells with SAT overexpression, although no such sites
      were noted in the controls, which was consistent with the data from clinical
      specimens. A regression analysis revealed that the expression of SAT was
      significantly associated with the levels of hypomethylation of satellite alpha
      sequences. On the whole, the overexpression of SAT led to chromosomal instability
      via segregation errors at specific chromosomes in connection with DNA
      hypomethylation, which was also recognized in clinical specimens of patients with
      breast cancer. Thus, this oncogenic pathway may be involved in the development of
      breast cancer.

PMID- 29568895
TI  - Abnormal expression of fibrosis markers, estrogen receptor alpha and stromal
      derived factor-1/chemokine (C-X-C motif) receptor-4 axis in intrauterine
      adhesions.
AB  - Intrauterine adhesions (IUAs) are mainly derived from fibrous tissue formation
      following endometrial damage. The aim of the present study was to assess whether
      fibrosis markers, estrogen receptor (ER)alpha and the stromal derived factor
      (SDF)-1/C-X-C chemokine receptor type 4 (CXCR-4) axis are abnormally expressed in
      IUA endometrium. A total of 76 human endometrial biopsy samples (normal, n=20;
      mild-to-moderate IUAs, n=40; and severe IUAs, n=16) were employed, and Sprague
      Dawley rat IUA models at different time points were constructed. Subsequently,
      the expression of transforming growth factor (TGF)-beta1, matrix
      metalloproteinase (MMP)-9, ERalpha and the SDF-1/CXCR-4 axis was evaluated in
      human and rat IUAs using histology, immunohistochemistry, reverse transcription
      quantitative polymerase chain reaction and western blotting. In patients and rats
      with IUA formation, the expression of TGF-beta1, MMP-9 and ERalpha was
      significantly higher compared with the control group at the mRNA and protein
      levels (P<0.05); in addition, in patients, the TGF-beta1, MMP-9 and ERalpha
      levels were significantly higher in severe IUAs compared with those in mild-to
      moderate IUA endometrium (P<0.05). Although the chemokine SDF-1 level in rats
      increased significantly during the early postoperative phase (reaching a peak at
      the second estrus phase) in rat endometrium (P<0.05), its special receptor CXCR-4
      expression did not differ significantly compared with the control group in rats
      or patients (P>0.05). Our findings indicated that aberrant activation of fibrosis
      and expression of ERalpha may be involved in the pathology of IUA formation. The
      role of the SDF-1/CXCR-4 axis in IUAs as inflammatory medium in the short-term or
      special homing factors for bone marrow mesenchymal stem cells requires further
      verification in in vivo animal models.

PMID- 29568897
TI  - miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via
      targeting PI3K/AKT signaling pathway.
AB  - Renal interstitial fibrosis is a necessary step in the progression of chronic
      kidney to end stage renal disease. MicroRNA-29 (miR-29) has been shown to play
      essential roles in epithelial-mesenchymal transition (EMT), and thus may
      contribute to the regulation of renal interstitial fibrosis. However, the role of
      miR-29 in the regulation of EMT during chronic kidney disease and renal
      transplantation has been a source of intense debate, and the mechanisms
      underlying this process are incompletely understood. In this study, we
      investigated the function of miR-29b in the regulation of EMT and to gain a
      better understanding of the mechanism by which miR-29b modulates EMT by targeting
      the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway
      during the process of renal interstitial fibrosis. The rat proximal tubular
      epithelial cell line NRK-52E was cultured in DMEM and treated with angiotensin II
      (Ang II) at various concentrations. RT-PCR was performed to investigate changes
      in the levels of expression of miR-29b in NRK-52E cells and western blotting was
      used to analyze the expression of PI3K, p-AKT, vimentin and keratin 18. The
      result of the study show that treatment of NRK-52E cells with Ang II induced the
      transition of the cellular phenotype from epithelial to mesenchymal and
      upregulated the PI3K/AKT signaling pathway; this was also found following
      treatment with a phosphatase and tensin homolog on chromosome 10 (PTEN)-specific
      inhibitor. Increased expression of miR-29b was able to reverse the phenotype
      induced by Ang II in NRK-52E cells and blocking miR-29b activity with an miR-29b
      inhibitor resulted in enhanced EMT. Additionally, the PI3K/AKT signaling pathway
      was found to be suppressed in the presence of enhanced expression of miR-29b by
      direct binding to 3'-untranslated region (3'-UTR) of PIK3R2. We concluded that
      miR-29b plays an important role in the negative regulation of Ang II-induced EMT
      via PI3K/AKT signaling pathway and propose that enhancing miR-29b level or
      blocking PI3K/AKT signaling pathway may be a novel therapeutic target in renal
      interstitial fibrosis.

PMID- 29568896
TI  - Peroxisome proliferator-activated receptor-gamma and its related pathway in bone
      marrow mesenchymal stem cell differentiation co-cultured with mechanically
      stretched ligament fibroblasts.
AB  - The occurrence of pelvic floor dysfunctional disease (PFD) is closely related
      with elasticity, toughness, and functional changes of the connective tissue of
      the pelvic support tissue. Bone marrow mesenchymal stem cells (BMSCs) have been
      confirmed to have the capacity to differentiate into a variety of cell types such
      as osteoblasts, chondroblasts, adipocytes and fibroblasts. Therefore, BMSCs have
      the potential to improve the clinical outcomes for PFD. Peroxisome proliferator
      activated receptor-gamma (PPAR-gamma), a ligand activated transcription factor,
      has acquired a great deal of attention as it is involved in the fibrosis and cell
      differentiation. However, how it is regulated during the process of the
      differentiation of BMSCs into fibroblasts remains to be defined. The present
      study investigated the underlying mechanisms of PPAR-gamma effect of mechanical
      stretch on the differentiation of BMSCs induced by pelvic ligament fibroblasts.
      PPAR-gamma expression was decreased during the differentiation of BMSCs into
      fibroblasts by co-cultured stretched fibroblasts. Addition of transforming growth
      factor-beta1 (TGF-beta1) reduced PPAR-gamma expression and promoted the
      differentiation of BMSCs. With the employment of endogenous ligand, activation of
      PPAR-gamma suppressed the BMSC differentiation. Similar effects were also
      observed with overexpression of PPAR-gamma gene. In addition, decrease of PPAR
      gamma by the use of shRNA targeting rat PPAR-gamma significantly contributed to
      BMSC differentiation to fibroblasts. These results indicate that PPAR-gamma
      negatively regulates the differentiation of BMSCs into fibroblasts.

PMID- 29568898
TI  - Adiponectin protects against lung ischemia-reperfusion injury in rats with type 2
      diabetes mellitus.
AB  - Adiponectin (APN) has been associated with the pathogenesis of acute brain, liver
      and heart injury. However, the role of APN in lung ischemia-reperfusion injury
      (LIRI) in diabetes mellitus remains unclear. To investigate this, the present
      study evaluated the effects of APN on lung dysfunction and pathological
      alterations in rats with type 2 diabetes mellitus via lung ischemia/reperfusion
      (I/R). The lung-protective effects of APN globular domain (gAPN) in rats with
      type 2 diabetes mellitus were also investigated by measuring the oxygenation
      index, inflammatory cytokines, lung edema, histopathology, oxidative stress,
      apoptosis and the protein expression levels of phosphorylated 5'adenosine
      monophosphate-activated protein kinase (p-AMPK), endothelial nitric oxide
      synthase (eNOS) and inducible nitric oxide synthase (iNOS). The results of the
      present study demonstrated that the diabetes mellitus rats + I/R (DIR) group
      exhibited greater concentrations of tumor necrosis factor-alpha and interleukin
      6, and increases in the wet-weight to dry-weight ratio, lung injury score,
      oxidative stress and cellular apoptosis. These effects were accompanied by lower
      pulmonary oxygenation compared with the normal rat + I/R (NIR) group (P<0.05).
      Additionally, all of these alterations were attenuated in the NIR + gAPN and DIR
      + gAPN groups compared with in the NIR and DIR groups, respectively. In the DIR
      group, the expression levels of p-AMPK/AMPK and eNOS were significantly
      downregulated, and the levels of iNOS were upregulated, compared with those of
      the NIR group. Treatment with APN activated AMPK, increased eNOS expression and
      attenuated iNOS expression. The results of the present study demonstrated that
      APN exerted protective effects against LIRI via its anti-inflammatory,
      antioxidative stress and anti-apoptotic activities. These protective effects of
      APN were eliminated in rats with type 2 diabetes mellitus, in which LIRI was
      exacerbated. The present study indicated that APN may be a potential therapeutic
      agent for LIRI in type 2 diabetes mellitus.

PMID- 29568899
TI  - Role of epithelial chemokines in the pathogenesis of airway inflammation in
      asthma (Review).
AB  - As the first barrier to the outside environment, airway epithelial cells serve a
      central role in the initiation and development of airway inflammation. Chemokines
      are the most direct and immediate cell factors for the recruitment and migration
      of inflammatory cells. The present review focused on the role of epithelial
      chemokines in the pathogenesis of airway inflammation in asthma. In addition to
      traditional CC family chemokines and CXC family chemokines, airway epithelial
      cells also express other chemokines, including thymic stromal lymphopoietin and
      interleukin-33. By expressing and secreting chemokines, airway epithelial cells
      serve a key role in orchestrating airway inflammation in asthma.

PMID- 29568900
TI  - Glucosamine promotes chondrocyte proliferation via the Wnt/beta-catenin signaling
      pathway.
AB  - The present study investigated the mechanism underlying the effects of
      glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee
      cartilage of Sprague-Dawley rats. Chondrocytes were treated with various
      concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte
      proliferation were determined using reverse transcription-polymerase chain
      reaction, western blot analysis and immunohistochemistry. The results indicated
      that GlcN significantly improved chondrocyte viability, accelerated G1/S
      transition during progression of the cell cycle and promoted the expression of
      cell cycle regulatory proteins, including cyclin D1, cyclin-dependent kinase
      (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation.
      Furthermore, GlcN upregulated the expression levels of Wnt-4, Frizzled-2 and beta
      catenin, and downregulated the expression of glycogen synthase kinase-3. GlcN
      also promoted beta-catenin translocation; beta-catenin is able to activate
      numerous downstream target genes, including cyclin D1. To determine the role of
      the Wnt/beta-catenin signaling pathway in chondrocyte proliferation, the Wnt/beta
      catenin signaling pathway was inhibited using Dickkopf-1 (DKK-1), after which
      chondrocytes were treated with GlcN. The results demonstrated that the expression
      levels of beta-catenin and cyclin D1 were decreased in chondrocytes treated with
      DKK-1 and GlcN. These results suggested that GlcN may promote chondrocyte
      proliferation via the Wnt/beta-catenin signaling pathway.

PMID- 29568901
TI  - Puerarin promotes MIN6 cell survival by reducing cellular reactive oxygen
      species.
AB  - Type 1 diabetes is caused by destruction of the pancreatic beta-cells and, to
      date, no cure has been developed. Promoting the survival of pancreatic beta-cells
      may be beneficial for patients with type 1 diabetes. Puerarin is an estrogen
      analogue that been demonstrated in previous studies to be able to decreased blood
      glucose in patients with type 1 diabetes. Similar results were demonstrated in
      previous studies which additionally demonstrated that puerarin was able to
      decreased blood glucose in type 1 diabetic mice by protecting pancreatic beta
      cells. However, the mechanism underlying the function of puerarin in pancreatic
      beta-cells remains unclear. Therefore, the present study sought to investigate
      the detailed function of puerarin in pancreatic beta-cells. In the present study,
      H2O2 was used to induce apoptosis. It was observed that puerarin significantly
      decreased H2O2-induced apoptosis in mouse insulinoma MIN6 cells. It was
      additionally observed that puerarin decreased the levels of intracellular
      reactive oxygen species and mitochondrial superoxide in MIN6 cells. The
      protective effect of puerarin was markedly decreased by 6-aminonicotinamide, an
      inhibitor of glucose-6-phosphate dehydrogenase (G6PD). In conclusion, the results
      of the present study suggested that puerarin may increase the activity of G6PD,
      decreased the level of oxidative stress in MIN6 cells, protect mitochondria and
      promote MIN6 cell survival. Investigating the mechanism underlying the effect of
      puerarin in MIN6 cells may provide a novel approach for development of a cure for
      type 1 diabetes.

PMID- 29568902
TI  - Dauricine inhibits viability and induces cell cycle arrest and apoptosis via
      inhibiting the PI3K/Akt signaling pathway in renal cell carcinoma cells.
AB  - Renal cell carcinoma (RCC), which is derived from the proximal tubules of
      nephrons, is one of the most common solid cancers. Due to its inherent
      insensitivity to radiotherapy and chemotherapy, surgery remains the only curative
      strategy for RCC. Therefore, a novel strategy for treating RCC is urgently
      needed. This study aims to investigate the effects of dauricine, a
      bisbenzylisoquinoline alkaloid, in RCC cells and the underlying mechanisms of its
      action. The effects of dauricine on viability, cell cycle distribution and
      apoptosis in RCC cells were determined in vitro by MTT assay, flow cytometry and
      nucleosome ELISA assay, respectively. Mechanism studies were performed by
      analyzing related proteins using western blotting assays. We show that dauricine
      effectively inhibits the viability of four RCC cell lines (786-O, Caki-1, A-498
      and ACHN). In addition, dauricine induces cell cycle arrest at the G0/G1 phase in
      RCC cells. Dauricine also induces apoptosis via the intrinsic pathway, since
      caspase-9 and caspase-3 but not caspase-8 activation was detected after the
      treatment. Moreover, dauricine was able to inhibit the PI3K/Akt signaling
      pathway. Our findings suggest inhibitory effects of dauricine in renal cancer
      cells and provide a better understanding of its underlying mechanism. Our
      findings suggest that dauricine could be a potential therapeutic agent for
      treating RCC.

PMID- 29568903
TI  - PPARalpha activation alleviates damage to the cytoskeleton during acute
      myocardial ischemia/reperfusion in rats.
AB  - The cytoskeleton serves an important role in maintaining cellular morphology and
      function, and it is a substrate of calpain during myocardial ischemia/reperfusion
      (I/R) injury (MIRI). Calpain may be activated by endoplasmic reticulum (ER)
      stress during MIRI. The activation of peroxisome proliferator-activated receptor
      alpha (PPARalpha) may inhibit ischemia/reperfusion damage by regulating stress
      reactions. The present study aimed to determine whether the activation of
      PPARalpha protects against MIRI-induced cytoskeletal degradation, and
      investigated the underlying mechanism involved. Wistar rats were pretreated with
      or without fenofibrate and subjected to left anterior descending coronary artery
      ligation for 45 min, followed by 120 min of reperfusion. Calpain activity and the
      expression of PPARalpha, desmin and ER stress parameters were evaluated.
      Electrocardiography was performed and cardiac function was evaluated. The
      ultrastructure was observed under transmission electron microscopy. I/R
      significantly induced damage to the cytoskeleton in cardiomyocytes and cardiac
      dysfunction, all of which were improved by PPARalpha activation. In addition, I/R
      increased ER stress and calpain activity, which were significantly decreased in
      fenofibrate-pretreated rat heart tissue. The results suggested that PPARalpha
      activation may exert a protective effect against I/R in the myocardium, at least
      in part via ER stress inhibition. Suppression of ER stress may be an effective
      therapeutic target for protecting the I/R myocardium.

PMID- 29568904
TI  - Roles of elevated 20-HETE in the breakdown of blood brain barrier and the
      severity of brain edema in experimental traumatic brain injury.
AB  - Breakdown of the blood brain barrier (BBB) is a secondary injury following
      traumatic brain injury (TBI) and can lead to the development of brain edema.
      However, the factors that contribute to the disruption of the BBB and increase
      the severity of brain edema in TBI remain to be elucidated. 20
      hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid. The
      inhibition of 20-HETEsynthesis by HET0016 has been suggested as a strategy to
      decrease brain edema. The present study aimed to investigate whether the elevated
      production of 20-HETE in cerebral tissue may contribute to BBB breakdown and
      increase the severity of brain edema in rats with TBI. BBB permeability was
      quantified using dynamic contrast-enhanced magnetic resonance imaging and brain
      edema was measured according to brain water content. Superoxide production in
      injured tissue was also assessed. Liquid chromatography-mass spectrometry was
      used to evaluate 20-HETE production in injured tissue. Western blot analysis was
      used to assess the expression of occludin, zonula occludens (ZO)-1, matrix
      metalloproteinase (MMP)-9, and proteins of the c-Jun N-terminal kinase (JNK)
      pathway. A total of 3, 24 and 72 h following the induction of TBI, 20-HETE
      levels, BBB permeability and brain edema were identified to be increased,
      accompanied by an increase in superoxide production. Conversely, superoxide
      dismutase levels, in addition to the total antioxidative capability were
      decreased. In addition, the expression of MMP-9 and proteins of the JNK pathway
      was upregulated, whereas the expression of occludin and ZO-1 was observed to be
      suppressed. These results suggested that 20-HETE may aggravate BBB disruption
      following TBI, via enhancing the expression of MMP-9 and tight junction proteins.
      Furthermore, oxidative stress and the JNK signaling pathway may be involved in
      BBB dysregulation. In conclusion, the results of the present demonstrated that
      the production of 20-HETE was increased in cerebral tissue following traumatic
      injury, thus suggesting that it may contribute to the compromise of BBB integrity
      and the development of brain edema.

PMID- 29568905
TI  - Myricitrin ameliorates ethanol-induced steatosis in mouse AML12 liver cells by
      activating AMPK, and reducing oxidative stress and expression of inflammatory
      cytokines.
AB  - It is necessary to identify compounds that may provide protection against
      alcoholic liver disease. To the best of our knowledge, the effect of myricitrin
      on the development of ethanol-induced liver disease has not been previously
      investigated. The present study aimed to determine the effect of myricitrin on
      ethanol-induced steatosis in AML12 mouse liver cells and to identify the
      underlying molecular mechanisms. Ethanol-treated AML12 cells exhibited
      significant improvement in viability following treatment with myricitrin. Oil red
      O staining indicated that myricitrin ameliorated ethanol-induced lipid
      accumulation in cells. Furthermore, following treatment with myricitrin,
      improvement in ethanol-induced steatosis and decrease in the levels of reactive
      oxygen species and lipoperoxides were observed in ethanol-stimulated cells.
      Myricitrin suppressed mRNA and protein expression of tumor necrosis factor-alpha,
      interleukin-6 and transforming growth factor-beta1 in ethanol-stimulated AML12
      cells. Myricitrin markedly increased phosphorylation of adenosine monophosphate
      activated protein kinase (AMPK) and significantly reduced mRNA expression of
      sterol-regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase
      in ethanol-stimulated AML12 cells. The results of the present study indicate that
      myricitrin ameliorates ethanol-induced steatosis in AML12 cells by attenuating
      oxidative stress, suppressing expression of certain inflammatory cytokines and
      modulating the AMPK/SREBP-1c pathway.

PMID- 29568906
TI  - miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole
      on acute kidney injury in a mouse model of disseminated candidiasis.
AB  - Previous studies have indicated that monocyte chemoattractant protein-1 (MCP-1),
      also referred to as C-C motif chemokine ligand 2, has a significant role in the
      pathogenesis of sepsis, however, how microRNAs (miRs) contribute to this process
      remains to be fully elucidated. In the present study, using a mouse model of
      disseminated candidiasis, the renoprotective effect of itraconazole (ITR) and
      adenovirus-delivered miR-124 was investigated. The mice were treated with ITR (50
      mg/kg) or transfected with miR-124 mimics via tail-vein injection 7 days prior to
      Candida albicans infection. The survival outcome was monitored following
      candidiasis-induced sepsis with ITR or miR-124 mimics treatment. The levels of
      pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and IL-6, were determined using enzyme-linked
      immunosorbent assays. The mRNA and protein levels were assayed using reverse
      transcription-quantitative polymerase chain reaction and western blot analyses,
      respectively. The results showed that ITR and miR-124 mimics improved the
      survival outcome in candidiasis-induced septic mice. The findings also indicated
      a significant downregulation in the serum levels of TNF-alpha, IL-1beta and IL-6
      in the septic mice treated with ITR or miR-124 mimics. Of note, ITR treatment
      significantly increased the expression of miR-124 and decreased the levels of MCP
      1 in the kidneys of the septic mice. It was also shown that the overexpression of
      miR-124 reduced the expression of MCP-1 and attenuated candidiasis-induced acute
      kidney injury (AKI) in septic mice. Transfection with miR-124 mimics was
      equivalent to ITR in reducing the excessive inflammatory response and renal
      lesions in septic mice. These results provided evidence supporting the use of miR
      124 mimics as a therapeutic approach for attenuating candidiasis-induced AKI.

PMID- 29568907
TI  - Differential modulation by vanadium pentoxide of the secretion of CXCL8 and
      CXCL11 chemokines in thyroid cells.
AB  - Recently it has been hypothesized that vanadium serves a carcinogenic role in the
      thyroid. However, to date, no in vivo or in vitro studies have evaluated thyroid
      disruption in humans and/or animals following exposure to vanadium. The present
      study evaluated the effect of vanadium pentoxide (V2O5) on cell viability and
      proliferation, and chemokine (C-X-C motif) ligand (CXCL)8 and CXCL11 secretion in
      normal thyrocytes. The results demonstrated that V2O5 had no effect on thyroid
      follicular cell viability and proliferation. However, V2O5 was able to induce the
      secretion of CXCL8 and CXCL11 chemokines from thyrocytes. Notably, V2O5
      synergistically increased the effect of the interferon (IFN)-gamma on CXCL11
      secretion. In addition, V2O5 synergistically increased the effect of tumor
      necrosis factor-alpha on CXCL8 secretion, and abolished the inhibitory effect of
      IFN-gamma. Overall this induction of CXCL8 and CXCL11 secretion may lead to the
      induction and perpetuation of an inflammatory reaction in the thyroid. Further
      studies are now required to evaluate thyroid function and nodule development in
      subjects who are occupationally exposed, or living in polluted areas.

PMID- 29568908
TI  - Quercetin inhibits NTHi-triggered CXCR4 activation through suppressing
      IKKalpha/NF-kappaB and MAPK signaling pathways in otitis media.
AB  - Otitis media is one of the most common bacterial infections in children,
      contributing to hearing loss. A vital bacterial pathogen leading to otitis media
      development is the nontypeable Haemophilus influenzae (NTHi). Inflammation
      response is reported as an important characristic for otitis media. Chemokine CXC
      receptor 4 (CXCR4) is a 352-amino acid seven-span transmembrane G-protein coupled
      receptor, essential for inflammatory response. However, the possible molecular
      mechanism indicating the alteration of CXCR4 modulated by NTHi is poorly known.
      In the present study, NTHi enhanced CXCR4 expression through phosphorylation of
      IKKalpha and p38, which relied on nuclear factor-kappaB (NF-kappaB) translocation
      in vitro as well as in the middle ear of mice in vivo. Previously, quercetin, a
      natural production mainly isolated from rutin, has shown anti-inflammatory
      effects. Here, we report that quercetin suppressed NTHi-induced CXCR4 expression
      levels in vitro and in vivo. Quercetin blocked CXCR4 activation through direct
      IKKbeta phosphorylation inhibition, as well as of p38 MAPK restraining. Hence,
      identification of quercetin may be a potential therapeutic strategy for treating
      otitis media induced by NTHi through inflammation suppression.

PMID- 29568909
TI  - Hyperthermia inhibits the motility of gemcitabine-resistant pancreatic cancer
      PANC-1 cells through the inhibition of epithelial-mesenchymal transition.
AB  - Pancreatic cancer (PC) is one of the most common types of malignant tumor and the
      leading cause of cancer-associated mortality worldwide. The chemotherapeutic drug
      gemcitabine (GEM) is used as a first-line chemotherapeutic agent for advanced PC.
      However, the acquisition of drug resistance is a major limitation of the clinical
      effect of GEM and commonly leads to increased metastasis. The occurrence of
      epithelial-mesenchymal transition (EMT) has been demonstrated to be the
      underlying mechanism of acquired resistance. It has been reported that heat
      treatment is able to inhibit EMT in pancreatic adenocarcinoma cells. In the
      present study the effect of hyperthermia on the sensitivity of GEM-resistant PC
      cells was investigated. First a GEM-resistant PC cell line PANC-1 (PAN/GEM) was
      developed and it was demonstrated that drug resistant PAN/GEM cells exhibited
      significantly increased migratory and invasive abilities compared with control
      PANC-1 cells using a Transwell assay. EMT was induced in resistant PAN/GEM cells,
      followed by reduced epithelial marker epithelial (E)-cadherin expression and
      increased mesenchymal marker Vimentin expression compared with control PANC-1
      cells. Next, the Transwell assay demonstrated that the hyperthermia at 42C for 1
      h combined with GEM significantly attenuated migration and invasion in drug
      resistant PAN/GEM cells, while GEM alone treatment did not significantly affect
      the migration and invasion. Additionally, EMT in PAN/GEM cells was reversed by
      hyperthermia, as demonstrated by the restoration of E-cadherin and downregulation
      of mesenchymal markers Vimentin, matrix metalloproteinase (MMP)2 and MMP9.
      Furthermore, an MMP2 inhibitor tissue inhibitor of metalloproteinases (TIMP)2 and
      MMP9 inhibitor TIMP1 were used to treat PAN/GEM cells and it was demonstrated
      that both inhibitors increased the inhibition of hyperthermia treatment combined
      with GEM on cell invasion, suggesting an association between cell invasion and
      MMP2, and MMP9. Additionally, proliferation of PAN/GEM cells following
      hyperthermia was assessed using an MTT assay. The results demonstrated that
      proliferation in PAN/GEM cells treated with hyperthermia was significantly
      inhibited by GEM compared with GEM alone treated cells, indicating that
      hyperthermia enhanced the inhibition of GEM on cell growth and resensitized the
      drug-resistant cells to GEM. Overall, the results of the present study suggested
      that hyperthermia is able to resensitize GEM-resistant PANC-1 cells to GEM by
      reversing EMT via the regulation of EMT-associated factors, therefore inhibiting
      cell migration and invasion.

PMID- 29568910
TI  - Downregulation of miR-374b-5p promotes chemotherapeutic resistance in pancreatic
      cancer by upregulating multiple anti-apoptotic proteins.
AB  - Resistance to first-line chemotherapeutic drugs such as gemcitabine contributes
      to the poor prognosis of patients with pancreatic cancer. MicroRNAs (miRNA)
      regulate chemoresistance in pancreatic cancer. By analyzing the miRNA sequencing
      dataset of pancreatic cancer from The Cancer Genome Atlas, it was demonstrated
      that miR-374b-5p expression was dramatically reduced in pancreatic cancer tissues
      compared with adjacent normal tissues, as well as decreased in chemoresistant
      compared with chemosensitive pancreatic carcinoma tissues. The decreased
      expression of miR-374-5p was associated with poor overall and progression-free
      survival in patients with pancreatic cancer. Furthermore, increased expression of
      miR-374b-5p abrogated, while the silencing miR-374b-5p increased the
      chemoresistance of pancreatic cancer cells to gemcitabine in vitro. Importantly,
      the upregulation of miR-374b-5p ameliorated the chemoresistance of pancreatic
      cancer cells to gemcitabine in vivo. It was also demonstrated that miR-374b-5p
      targeted several anti-apoptotic proteins, including B-cell lymphoma 2,
      Baculoviral IAP Repeat Containing 3 and X-linked inhibitor of apoptosis in
      pancreatic cancer cells, which further attenuated chemoresistance in pancreatic
      cancer. Therefore, the results of the current study indicate that miR-374b-5p
      serves as a potential diagnostic marker. It also suggests that miR-374b-5p
      sensitizes cells to chemotherapy and may be used in combination with
      chemotherapeutic agents such as gemcitabine to treat patients with pancreatic
      cancer.

PMID- 29568912
TI  - Clinical study of prenatal ultrasonography combined with T-box transcription
      factor 1 as a biomarker for the diagnosis of congenital heart disease.
AB  - Congenital heart disease (CHD) seriously threatens fetal health. Therefore,
      prenatal examination to detect deformity is extremely important. The present
      study aimed to investigate the clinical application value of prenatal
      ultrasonography combined with molecular biology methods in the diagnosis of fetal
      CHD. A total of 1,000 pregnant women who had received fetal ultrasonography to
      examine fetal CHD were enrolled. Ultrasounds were performed for fetal heart
      examination and diagnosis, mainly on fetal heart position, size, structure and
      function, and heart valve morphology and function. These indexes were tested
      again 2 weeks after birth. Blood samples were collected from pregnant women with
      fetal CHD. Polymerase chain reaction (PCR) and western blotting were performed to
      detect the association between heart development and T-box transcription factor 1
      (TBX1) expression. The results revealed that 10 fetuses had CHD (1%), of which
      ultrasound detected 9 cases. The specificity and sensitivity of ultrasounds were
      100 and 90%, respectively. Of the 9 cases were identified by prenatal ultrasound
      screening, including 2 cases had endocardial cushion defect, 1 case had pulmonary
      stenosis combined with right ventricular dysplasia, 1 case had tetralogy of
      Fallot combined with a cleft lip and palate, 2 cases had ventricular septal
      defect, 1 case had a single ventricle defect, 1 case had Ebstein and 1 case had a
      triatrial heart. One case of ventricular septal defect was missed prior to
      delivery. PCR and western blotting demonstrated that TBX1 expression may be
      associated with CHD. Therefore, ultrasonography combined with laboratory
      examinations represent efficient, economic and safe methods for fetal CHD
      detection. These methods may be significant to improve the rate of CHD diagnosis,
      and require further investigation.

PMID- 29568911
TI  - miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells
      via ERK signaling pathway by inhibiting KLF4.
AB  - In recent years, microRNAs (miRNAs/miRs) have gained increasing interest in
      cancer research. Increasing evidences demonstrated that miRNAs are important for
      tumor early detection and prognosis. The present study aimed to explore the
      function of miR-25 in non-small-cell lung cancer (NSCLC) and its underlying
      mechanisms. The expression levels of miR-25 and Kruppel-like factor 4 (KLF4) were
      assessed in 31 pairs of tissue from patients with NSCLC. In addition, the
      biological roles of miR-25 in NSCLC were analyzed via a cell wound healing assay,
      Transwell invasion and migration assays. Target genes of miR-25 were predicted
      using TargetScan and verified via a dual luciferase activity assay, western
      blotting and reverse transcription-quantitative polymerase chain reaction. The
      downstream signaling pathway was confirmed by western blot analysis. In the
      present study, miR-25 was overexpressed in 31 NSCLC samples compared with in
      corresponding normal tissues. Overexpression of miR-25 using miR-25 mimics
      markedly promoted NSCLC cell migration and invasion, while inhibition of miR-25
      exerted the opposite effect. KLF4 was suggested to be a novel target gene of miR
      25 in NSCLC cells. Knockdown of KLF4 promoted the migration and invasion of NSCLC
      cells, whereas rescue of KLF4 expression reduced cell motion ability in miR-25
      overexpressing NSCLC cells. Furthermore, it was demonstrated that miR-25
      activated the extracellular signal-regulated kinase (ERK) signaling pathway,
      which eventually led to increased vimentin, matrix metalloproteinase 11 and N
      cadherin levels, and the downregulation of E-cadherin expression by inhibiting
      the expression of KLF4. In conclusion, miR-25 was demonstrated to activate the
      ERK signaling pathway by directly targeting KLF4, promoting cell migration and
      invasion. The findings of the present study indicated that miR-25 or KLF4 may
      serve as a therapeutic target for the treatment of NSCLC.

PMID- 29568913
TI  - A novel therapeutic strategy of personalized medicine based on anti-epidermal
      growth factor receptor monoclonal antibodies in patients with metastatic
      colorectal cancer.
AB  - Achieving tumor shrinkage may be a clinically relevant improvement in the
      treatment of metastatic colorectal cancer (mCRC). The present study attempted to
      evaluate early tumor shrinkage (ETS) and deepness of response over 6-8 courses of
      therapy, which were assessed previously in first-line trials of anti-epidermal
      growth factor receptor (EGFR) monoclonal antibodies. A total of 37 patients with
      mCRC that was considered unresectable or borderline resectable were enrolled in
      the study. Patients exhibited the wild-type RAS gene, and anti-EGFR monoclonal
      antibodies were used as the first-line treatment in the Department of Surgical
      Oncology at Gifu University School of Medicine (Gifu, Japan) between January 2010
      and March 2017. Tumor shrinkage and other characteristics were evaluated
      according to the Response Evaluation Criteria In Solid Tumors (RECIST)
      classifications (version 1.1). The 3-year overall survival (OS) rate was >60.0%
      for all cases (n=37). The mean tumor shrinkage rate in the right side of the
      colon according to the RECIST classifications was -11.1%, whereas that for CRC on
      the left side showed a statistically significant difference at -54.0% (P=0.042).
      In addition, the rates of OS for stable disease + progressive disease compared
      with partial response + complete response, and those of OS for conversion therapy
      compared with non-conversion therapy were significantly different (both P<0.001).
      Carcinoembryonic antigen (CEA) was suggested to be a possible predictive factor
      for convalescence due to the 50% drop in its value after the 6-8 courses of
      therapy. Overall, the predictive performance of ETS with respect to PFS and OS is
      at least as good as the standard RECIST response, with the advantage of an
      earlier assessment, and this may improve convalescence, with CEA as a marker in
      support of ETS over a clinical treatment course. In RAS wild-type patients, it is
      important to evaluate the rate of tumor shrinkage from the beginning of the first
      line treatment until 6-8 courses of anti-EGFR monoclonal antibodies have been
      administered.

PMID- 29568914
TI  - Tumor necrosis factor-alpha-induced protein 8-like-2 is involved in the
      activation of macrophages by Astragalus polysaccharides in vitro.
AB  - In previous years, studies have shown that Astragalus polysaccharides (APS) can
      improve cellular immunity and humoral immune function, which has become a focus
      of investigations. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2)
      is a negative regulator of immune reactions. However, the effect and underlying
      mechanisms of TIPE2 on the APS-induced immune response remains to be fully
      elucidated. The present study aimed to examine the role of TIPE2 and its
      underlying mechanisms in the APS-induced immune response. The production of
      nitric oxide (NO) was detected in macrophages in vitro following APS stimulation.
      In addition, the present study interfered with the expression of TIPE2 in
      macrophages, and examined the production of cytokines, NO and components of the
      mitogen-activate protein kinase (MAPK) signaling pathway following APS
      stimulation. The results showed that APS was able to activate macrophages by
      inducing the production of interleukin (IL)-1beta, tumor necrosis factor (TNF)
      alpha, IL-6 and NO. Furthermore, RAW264.7 cells were stimulated with APS when
      TIPE2 was silenced, and it was found that the production of TNF-alpha, IL-6, IL
      1beta and NO were upregulated, and the signaling pathway of MAPK was activated.
      Taken together, these results demonstrated that TIPE2 had an important negative
      effect on the APS-induced production of inflammatory cytokines and NO via the
      MAPK signaling pathway.

PMID- 29568915
TI  - Aspirin modulates the inflammatory response in a thrombus-stimulated LMVEC model.
AB  - The purpose of the present study was to examine whether aspirin interferes with
      the inflammatory response in a thrombus-stimulated lung microvascular endothelial
      cell (LMVEC) model. The LMVECs were randomly divided into eight groups: Normal
      group (group N), model group (group M), model + ASP group (group M+A),
      model+CX3CL1-short hairpin (sh)RNA group (group M+SH), model + CX3CL1
      overexpression vector group (group M+CX3), model + ASP + shRNA group (group
      M+A+SH), model + ASP + CX3CL1-overexpression vector group (group M+A+CX3), and
      normal + virus control group (group N+V). The endothelial cells were cultured,
      and a thrombus was added to the cells. Briefly, 12 h following the precipitation
      of the thrombus, data from ELISA, reverse transcription-quantitative polymerase
      chain reaction analysis and confocal microscopy revealed that the levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, CX3C chemokine ligand 1
      (CX3CL1), CX3C chemokine receptor 1 (CX3CR1) and nuclear factor-kappaB (NF
      kappaB) in group M were increased, compared with those in group N (P<0.01). These
      levels, with the exception of TNF-alpha, were significantly lower in group M+SH,
      compared with those in group M (P<0.01). Furthermore, the levels of IL-6 in
      groups M+A, M+CX3 and M+A+CX3 were decreased, compared with those in group M
      (P<0.01); the level of TNF-alpha in group M+A+SH was decreased, compared with
      that in group M (P<0.01); the level of CX3CR1 waslower in groups M+A and M+A+SH,
      compared with that in group M (P<0.01), and the level of NF-kappaB in group M+SH
      was decreased, compared with the level in group M and group M+A (P<0.05). In
      conclusion, the thrombus-stimulated LMVEC model exhibited induced production of
      TNF-alpha, IL-6, CX3CL, CX3CR1, NF-kappaB and intercellular adhesion molecule-1.
      Furthermore, it was confirmed that the signaling pathways involving CX3CL1-NF
      kappaB, IL-6 and TNF-alpha were partly inhibited by aspirin.

PMID- 29568916
TI  - miR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid
      fibroblasts.
AB  - Keloids are benign skin tumors that develop in individuals who have a positive
      family history of keloid disorders. Keloids are characterized by a deregulated
      wound-healing process, atypical fibroblasts with extreme deposition of
      extracellular matrix components, particularly collagen, increased cell
      proliferation and associated failure of apoptosis. Recently ingenol-mebutate has
      been used as a novel agent with anti-proliferative activity on human keloids as
      an alternative treatment option in patients, once conventional therapies have
      failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance
      between lesion formation and repair. A comprehensive understanding of the
      molecular mechanism underlying the Ingenol-mebutate response in keloid fibroblast
      following Ingenol-mebutate exposure has been established previously. Therefore,
      the present study analyzed changes in miRNAs and apoptotic gene regulation in
      Ingenol-mebutate treated keloid fibroblast, by reverse transcription-quantitative
      polymerase chain reaction and a DNA fragmentation assay. The range of upregulated
      miRNAs and downregulated genes encoding cell death appeared to be associated with
      the degree of the morphological alterations in Ingenol-mebutate treated keloids.
      In particular, the upregulation of miR-34a was detected in keloid fibroblasts
      during and following Ingenol-mebutate exposure. Keloid fibroblasts that
      overexpressed miR-34a showed differential expression of genes involved in the
      apoptotic signaling pathway such as p53. In conclusion, the Ingenol-mebutate
      treatment used here was effective in reducing keloid fibroblast growth in cell
      culture experiments and the expression of particular miRNAs modulated the pro
      apoptotic gene expression following Ingenol-mebutate treatment.

PMID- 29568917
TI  - EPB41L3 is a potential tumor suppressor gene and prognostic indicator in
      esophageal squamous cell carcinoma.
AB  - Although there have been reports about the role of erythrocyte membrane protein
      band 4.1 like 3 (EPB41L3) in several types of cancer, primarily in non-small-cell
      lung carcinoma, the molecular function and modulatory mechanisms of EPB41L3
      remain unclear. In specific, the functional and clinical significance of EPB41L3
      in esophageal squamous cell carcinoma (ESCC) has not been explored to date. In
      the present study, reduced EPB41L3 expression was demonstrated in ESCC cell lines
      and tissues, which was due to its high methylation rate. Ectopic expression of
      EPB41L3 in ESCC cells inhibited cell proliferation in vivo and in vitro. In
      addition, EPB41L3 overexpression induced apoptosis and G2/M cell cycle arrest by
      activating Caspase-3/8/9 and Cyclin-dependent kinase 1/Cyclin B1 signaling,
      respectively. Notably, patients with higher EPB41L3 expression had markedly
      higher overall survival rates compared with patients with lower EPB41L3
      expression. In summary, the present results suggest that EPB41L3 may be a tumor
      suppressor gene in ESCC development, representing a potential therapeutic target
      and a prognostic indicator for ESCC.

PMID- 29568918
TI  - Protection of Luteolin-7-O-glucoside against apoptosis induced by
      hypoxia/reoxygenation through the MAPK pathways in H9c2 cells.
AB  - Myocardial hypertrophy is often associated with myocardial infarction. Luteolin-7
      O-glucoside (LUTG) has the prosperity of preventing cardiomyocyte injury. The
      current study aimed to explore the potential protective effect of LUTG and its
      relevant mechanisms in the heart. To establish the cardiac hypertrophy model in
      vitro, Angiotensin II (Ang II) was used to stimuli H9c2 cells in this study. The
      CCK-8 assay showed that LUTG pretreatment improved cell viability of
      cardiomyocytes co-treated with Ang II and ischemia/reperfusion. LUTG decreased
      the reactive oxygen species levels. Furthermore, it was demonstrated LUTG could
      reduce the release amount of lactate dehydrogenase and recover the catalase
      activity according to the flow cytometry analysis, and activity detection,
      respectively in Ang II-H/R-treated H9c2 cells. In addition, the flow cytometry
      analysis showed that the pretreatment of LUTG mitigated cell apoptosis induced by
      hypoxia/reoxygenation in the cardiac hypertrophy model. Meanwhile, reverse
      transcription-quantitative polymerase chain reaction and western blot assays
      showed that the apoptosis-related genes, including poly (ADP-ribose) polymerase,
      Fas, Fasl and Caspase-3 were downregulated at the transcriptional and
      translational levels. Notably, the protien expression of phosphorylated (p)
      extracellular signal-regulated kinas (ERK) 1/2, p-janus kinase and p-P38 were
      reduced, while the expression of p-ERK5 was elevated in the LUTG pretreatment
      groups compared with the hypoxia/reoxygenation treatment group. Based on these
      results, it was suggested that the anti-apoptosis effect of LUTG may be
      associated with regulating the activation of mitogen-activated protein kinases
      signaling pathways.

PMID- 29568919
TI  - Downregulation of human choline kinase alpha gene expression by miR-876-5p.
AB  - Choline kinase (CK) is the first enzyme in the CDP-choline pathway for the
      synthesis of phosphatidylcholine, the most abundant phospholipid in the mammalian
      cell membrane. This enzyme exists as three isozymes (alpha1, alpha2 and beta) and
      the CKalpha isozyme has been implicated in cancer pathogenesis. Inhibition of CK
      activity has been proposed for cancer therapies. MicroRNAs (miRNAs/miRs) are non
      coding RNAs that serve important roles in diverse biological pathways and human
      diseases, including cancer. However, the regulation of CKalpha gene expression by
      miRNAs has never been investigated, to the best of the authors' knowledge. In the
      present study, two miRNA mimics, miR-876-5p and miR-646, were transfected into
      the HepG2 cell line and the effect of these miRNAs on the levels of CKalpha mRNA
      were determined by reverse transcription-quantitative polymerase chain reaction.
      Cells transfected with 25 nM miR-876-5p for 48 h exhibited significantly lower
      levels of CKalpha mRNA. Following optimization, miR-876-5p caused four times
      lower levels of CKalpha mRNA compared to the negative control. Effects of the
      miRNAs on HepG2 cell viability and cellular morphology were additionally analyzed
      using an MTT cell viability assay and scanning electron microscopy, respectively.
      HepG2 cells that were transfected with the optimum concentration of miR-876-5p
      for the optimum duration exhibited 25% lower viability than negative control and
      signs of apoptosis in electron micrographs. The results suggested miR-876-5p as a
      potential miRNA modulator of CKalpha expression in the cells, and may be relevant
      for the design of more effective anticancer strategy targeting CK.

PMID- 29568920
TI  - Oridonin induces apoptosis in oral squamous cell carcinoma probably through the
      generation of reactive oxygen species and the p38/JNK MAPK pathway.
AB  - The anti-inflammatory effects of oridonin (Ordn) have been well established in
      previous studies. However, the apoptotic effects of Ordn on oral cancer cells
      have not yet been evaluated, at least to the best of our knowledge. The aim of
      this study was to examine the apoptotic activity of Ordn in oral squamous cell
      carcinoma cells and to eluciudate the underlying mechanisms. For this purpose, we
      employed experimental techniques, such as MTT assay, DAPI staining, soft agar
      assay, flow cytometry and western blot analysis. Our results revealed that Ordn
      suppressed oral cancer cell proliferation and soft agar colony formation, while
      it induced reactive oxygen species (ROS)-dependent apoptosis in a dose or time
      dependent manner. The generation of ROS was detected in HN22 and HSC4 cells
      treated with Ordn and the use of the free radical scavenger, N-acetyl-L-cysteine,
      almost blocked Ordn-induced apoptosis. The phosphorylation of JNK and p38 mitogen
      activated protein kinase (MAPK) was manifested in the Ordn-treated cells.
      Furthermore, Ordn induced the apoptosis of oral cancer cells through the
      mitochondrial-dependent pathway, involving the loss of mitochondrial membrane
      potential, the release of cytochrome c, the induction of poly(ADP-Ribose)
      polymerase (PARP) cleavage, alterations in the ratios of apoptotic proteins and
      the activation of the caspase cascade. Taken together, these findings indicate
      that Ordn induces the apoptosis of oral cancer cells probably via ROS-mediated
      JNK/p38 MAPK and mitochondrial pathways; thus, Ordn may have potential for use in
      the treatment of oral cancer.

PMID- 29568921
TI  - Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF
      kappaB signaling pathway.
AB  - Asthma is a common chronic airway inflammation disease and is considered as a
      major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a
      naturally occurring flavonoid abundantly found in different vegetables and
      fruits. Fisetin has been reported to exhibit various positive biological effects,
      including anti-proliferative, anticancer, anti-oxidative and neuroprotective
      effects. We evaluated the effects of fisetin on allergic asthma regulation in
      mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA).
      Whether fisetin treatment attenuated OVA-induced airway inflammation was examined
      via inflammation inhibition through MyD88-related NF-kappaB (p65) signaling
      pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40
      (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results
      found that OVA-induced airway inflammation in mice caused a significant
      inflammatory response via the activation of MyD88 and NF-kappaB signaling
      pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin
      treated mice after OVA induction inhibited activation of MyD88 and NF-kappaB
      signaling pathways, resulting in downregulation of pro-inflammatory cytokine
      secretion. Further, fisetin significantly ameliorated the airway
      hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin
      reduced the number of eosinophil, monocyte, neutrophil and total white blood cell
      in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and
      BALF samples obtained from the OVA-induced mice with fisetin showed lower levels
      of pro-inflammatory cytokines. The results of our study illustrated that fisetin
      may be a new promising candidate to inhibit airway inflammation response induced
      by OVA.

PMID- 29568922
TI  - Phylogeny and polymorphism in the long control regions E6, E7, and L1 of HPV Type
      56 in women from southwest China.
AB  - Globally, human papillomavirus (HPV)-56 accounts for a small proportion of all
      high-risk HPV types; however, HPV-56 is detected at a higher rate in Asia,
      particularly in southwest China. The present study analyzed polymorphisms,
      intratypic variants, and genetic variability in the long control regions (LCR),
      E6, E7, and L1 of HPV-56 (n=75). The LCRs, E6, E7 and L1 were sequenced using a
      polymerase chain reaction and the sequences were submitted to GenBank. Maximum
      likelihood trees were constructed using Kimura's two-parameter model, followed by
      secondary structure analysis and protein damaging prediction. Additionally, in
      order to assess the effect of variations in the LCR on putative binding sites for
      cellular proteins, MATCH server was used. Finally, the selection pressures of the
      E6-E7 and L1 genes were estimated. A total of 18 point substitutions, a 42-bp
      deletion and a 19-bp deletion of LCR were identified. Some of those mutations are
      embedded in the putative binding sites for transcription factors. 18 single
      nucleotide changes occurred in the E6-E7 sequence, 11/18 were non-synonymous
      substitutions and 7/18 were synonymous mutations. A total 24 single nucleotide
      changes were identified in the L1 sequence, 6/24 being non-synonymous mutations
      and 18/24 synonymous mutations. Selective pressure analysis predicted that the
      majority of mutations of HPV-56 E6, E7 and L1 were of positive selection. The
      phylogenetic tree demonstrated that the isolates distributed in two lineages.
      Data on the prevalence and genetic variation of HPV-56 types in southwest China
      may aid future studies on viral molecular mechanisms and contribute to future
      investigations of diagnostic probes and therapeutic vaccines.

PMID- 29568923
TI  - ATM-JAK-PD-L1 signaling pathway inhibition decreases EMT and metastasis of
      androgen-independent prostate cancer.
AB  - Castration-resistant prostate cancer (CRPC), also known as androgen-independent
      prostate cancer, frequently develops local and distant metastases, the underlying
      mechanisms of which remain undetermined. In the present study, surgical specimens
      obtained from patients with clinical prostate cancer were investigated, and it
      was revealed that the expression levels of ataxia telangiectasia mutated kinase
      (ATM) were significantly enhanced in prostate cancer tissues isolated from
      patients with CRPC compared with from patients with hormone-dependent prostate
      cancer. CRPC C4-2 and CWR22Rv1 cells lines were subsequently selected to
      establish prostate cancer models, and ATM knockout cells were established via
      lentivirus infection. The results of the present study demonstrated that the
      migration and epithelial-mesenchymal transition (EMT) of ATM knockout cells were
      significantly decreased, which suggested that ATM is closely associated with CRPC
      cell migration and EMT. To further investigate the mechanisms underlying this
      process, programmed cell death 1 ligand 1 (PD-L1) expression was investigated in
      ATM knockout cells. In addition, inhibitors of Janus kinase (JAK) and signal
      transducer and activator of transcription 3 (STAT3; Stattic) were added to C4-2
      Sc and CWR22Rv1-Sc cells, and the results demonstrated that PD-L1 expression was
      significantly decreased following the addition of JAK inhibitor 1; however, no
      significant change was observed following the addition of Stattic. Furthermore, a
      PD-L1 antibody and JAK inhibitor 1 were added to C4-2-Sc and CWR22Rv1-Sc cells,
      and it was revealed that cell migration ability was significantly decreased and
      the expression of EMT-associated markers was effectively reversed. The results of
      the present study suggested that via inhibition of the ATM-JAK-PD-L1 signaling
      pathway, EMT, metastasis and progression of CRPC may be effectively suppressed,
      which may represent a novel therapeutic approach for targeted therapy for
      patients with CRPC.

PMID- 29568924
TI  - Downregulation of lncRNA H19 inhibits migration and invasion of human
      osteosarcoma through the NF-kappaB pathway.
AB  - The present study aimed to investigate the role of long non-coding RNA (lncRNA)
      H19 in the development of osteosarcoma and to determine the underlying mechanism
      involved. A total of 40 patients with osteosarcoma were selected and the
      expression level of H19 in tumor tissue and adjacent healthy tissue was detected
      by reverse transcription-quantitative polymerase chain reaction. Survival curves
      were plotted using the Kaplan-Meier method to investigate the prognostic value of
      H19 expression level for patients with osteosarcoma. H19 knockdown osteosarcoma
      cell lines were constructed using small interfering (si)RNA transfection. Cell
      migration and invasion abilities were measured by Transwell migration and
      invasion assays, respectively. Western blot analysis was performed to detect the
      expression levels of phosphatidylinositol 3-kinase (PI3K), phospho (p)-PI3K, RAC
      alpha serine/threonine-protein kinase (AKT), p-AKT and NF-kappaB inhibitor alpha
      (IkappaBalpha) in osteosarcoma cells transfected with H19 siRNA. Expression level
      of H19 was significantly elevated in tumor tissue compared with adjacent healthy
      tissue. Expression level of H19 was positively associated with distant metastasis
      of osteosarcoma (P<0.01), but not with gender and age. Overall survival of
      patients with osteosarcoma with high H19 level was significantly shorter compared
      with patients with low H19 expression (P<0.05). H19 knockdown significantly
      reduced migration and invasion ability of osteosarcoma cells. Significantly
      decreased levels of p-PI3K and p-AKT, and elevated level of IkappaBalpha were
      observed in H19 knockdown osteosarcoma cells compared with control osteosarcoma
      cells, while no significant differences in levels of PI3K and AKT were observed.
      Therefore, the present study demonstrated that knockdown of lncRNA H19 can
      inhibit migration and invasion of human osteosarcoma cells by inhibiting the
      nuclear factor-kappaB pathway.

PMID- 29568925
TI  - [Corrigendum] Altered expression of microRNA-98 in IL-1beta-induced cartilage
      degradation and its role in chondrocyte apoptosis.
AB  - Following the publication of this article, we realized that the joint first
      author's name had been printed incorrectly in the journal: This was mispelled as
      "Lingqing Chen". The corrected name (Lingqiang Chen) is featured here. We regret
      any inconvenience this has caused, and thank the Editor for allowing us the
      opportunity to publish a Corrigendum. [the original article was published in the
      Molecular Medicine Reports 16: 3208-3216, 2017; DOI: 10.3892/mmr.2017.7028].

PMID- 29568926
TI  - DNA methylation is related to the occurrence of breast cancer and is not affected
      by culture conditions.
AB  - The present study aimed to explore the relationship between DNA methylation and
      breast cancer under different cell culture conditions. MCF-7 breast cancer cells
      were cultured in two-dimensional (2D), three-dimensional (3D) and orthotopic
      transplantation (Ti) adhesion substrates. Principal component analysis (PCA) was
      used for global visualization of these three samples. The methylation status of
      CpG sites was examined by unsupervised clustering analysis. Scatter plots and
      histograms were constructed from the mean beta-values from 3D vs. 2D, 3D vs. Ti
      and Ti vs. 2D analysis. In addition, analyses of Gene Ontology (GO) terms and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted to explore
      the putative biological functions in which mutL homolog (MLH), phosphatase and
      tensin homolog (PTEN), runt-related transcription factor (RUNX), Ras association
      domain family (RASSF), cadherin 1 (CDH1), O-6-methylguanine-DNA methyltransferase
      (MGMT) and P16 may serve a role. Quantitative methylation-specific polymerase
      chain reaction (QMSP) was performed to determine the influence of culturing
      conditions on important gene expression. Results from PCA analysis indicated that
      the three samples were closely connected with each other. Venn diagrams revealed
      that certain differential methylation positions were common among the three
      sample groups, and 116 CpG positions were identified that appeared to be
      hypermethylated. The methylation patterns were more similar between 3D vs. 2D
      cultures compared with those between 3D vs. Ti or between Ti vs. 2D. Results of
      GO term and KEGG pathway analyses indicated that genes were enriched in four
      pathways, including transporter activity and G-protein coupled receptor activity.
      In addition, QMSP analysis identified no notable differences in the methylation
      status of MLH, PTEN, RUNX, RASSF, CDH1, MGMT and P16 under 2D, 3D and Ti culture
      conditions. In conclusion, abnormal DNA methylation is related with breast
      cancer, and the methylation status did not change in breast cancer cells cultured
      in different conditions.

PMID- 29568927
TI  - miR-185 and miR-29a are similarly expressed in the bronchoalveolar lavage cells
      in IPF and lung cancer but common targets DNMT1 and COL1A1 show disease specific
      patterns.
AB  - Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) constitute two
      progressively devastating lung diseases with common risk factors including aging
      and smoking. There is an increasing interest in the investigation of common
      pathogenic mechanisms between IPF and LC with therapeutic implications. Several
      oncomirs, microRNAs associated with malignancy, are also linked with IPF. miR-29a
      and miR-185 downregulation is probably involved both in carcinogenesis and
      fibrogenesis. We have previously observed miR-29a and miR-185 downregulation in
      IPF cells from bronchoalveolar lavage (BAL) and in this study we investigated
      their expression in LC BAL cells. Common targets of miR-29a and miR-185 such as
      DNA methyltransferase (DNMT)1, DNMT3b, COL1A1, AKT1 and AKT2 were measured.
      Potential correlations with pulmonary function tests, smoking status and
      endobronchial findings were investigated. Similar levels of miR-29a and miR-185
      were detected in IPF and LC while their common targets AKT1 and DNMT3b were not
      found to differ, suggesting potential pathogenetic similarities at the level of
      key epigenetic regulators. By conrast, COL1A1 mRNA levels were increased in IPF
      suggesting a disease-specific mRNA signature. Notably, DNMT1 was downregulated in
      the LC group and its expression was further reduced in the presence of increasing
      malignant burden as it was implied by the endobronchial findings.

PMID- 29568928
TI  - Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney
      injury in a mouse model by inhibiting oxidative stress and inflammatory
      responses.
AB  - Ursolic acid (UA) as a multiple bioactive native compound has recently been
      demonstrated to treat sepsis in animal models. However, the beneficial effects of
      UA in sepsis-induced acute kidney injury (AKI) are not completely understood. In
      the present study, the effect of UA on sepsis-induced AKI in cecal ligation and
      puncture (CLP) surgery mice was investigated. Renal histomorphological analysis
      was performed by hematoxylin and eosin staining. The expression of inflammatory
      markers in the kidney of septic mice was measured by reverse transcription
      quantitative polymerase chain reaction and western blotting. The results
      demonstrated that UA administration improved survival in septic mice induced by
      CLP surgery. The treatment with UA revealed protection against AKI induced by CLP
      surgery, including the alleviation of glomerular damage and vacuolization in the
      proximal tubules. In addition, the effects of UA on oxidative stress and
      inflammation in septic mice were determined. The findings suggested that UA may
      protect against sepsis-induced AKI by inhibiting reactive oxygen species and
      inflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)
      1beta and IL-6, in the kidney from septic mice. Finally, UA inhibited CLP-induced
      activation of nuclear factor-kappaB signaling in the kidney from septic mice. The
      findings of the present study demonstrated that UA may be used as a potential
      therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.

PMID- 29568929
TI  - Effect of KNDC1 overexpression on the senescence of human umbilical vein
      endothelial cells.
AB  - Kinase non-catalytic C-lobe domain containing 1 (KNDC1) exists in dendrites,
      guanine nucleotide exchange factor complexes and neuronal cell bodies as a
      putative protein-protein interaction module that regulates a number of signaling
      pathways. Previous studies have demonstrated that the knockdown of KNDC1 delays
      human umbilical vein endothelial cell (HUVEC) senescence. However, the effect of
      KNDC1 overexpression on HUVEC function remains unclear. In the present study, an
      adenovirus vector carrying KNDC1 was constructed and then transfected into
      endothelial cells to observe cell senescence. Furthermore, the effect of KNDC1
      overexpression on HUVEC senescence was investigated in vitro and the underlying
      molecular mechanism was investigated. Senescence-associated beta-galactosidase
      staining was used to determine cellular senescence and reactive oxygen species
      (ROS) were monitored to detect the level of cell oxidative stress. The mRNA
      transcription level and protein expression were analyzed by reverse transcription
      quantitative polymerase chain reaction and western blot analysis, respectively.
      The results demonstrated that KNDC1 overexpression possibly inhibited HUVEC
      activity and function and promoted HUVEC senescence. Mechanistic studies
      demonstrated that KNDC1 triggered a p53-ROS positive feedback loop, which serves
      a crucial role in regulating senescence. In conclusion, to the best of the
      authors' knowledge, this is the first time that KNDC1-adenovirus vector
      inhibition of HUVEC proliferation by activating the p53 signaling pathway has
      been reported. Theoretically, the results of the present study also support KNDC1
      as a therapeutic target for future anti-senescence.

PMID- 29568930
TI  - Angiopoietin-2 promotes extracellular matrix degradation in human degenerative
      nucleus pulposus cells.
AB  - In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become
      vascularized. Here, we determined the role of an angiogenesis promoter,
      angiopoietin (Ang)-2, in the pathology of IVD degeneration (IDD). We evaluated
      degree of IDD using the Pfirrmann grading system. We used quantitative real-time
      polymerase chain reaction and western blotting to analyze ANG2 gene expression
      and Ang-2 protein levels, respectively. The involvement of Ang-2 in IVD
      degradation and regulation of nuclear factor-kappaB (NF-kappaB) signaling was
      examined by immunohistochemistry, western blotting and immunofluorescence. As a
      result, 10 samples with grades II and III IDD were categorized as the mild IDD
      group; for comparison, another 10 specimens with grades IV and V constituted the
      severe IDD group. Ang-2 expression was significantly higher in severe IDD than in
      mild IDD. Exogenous Ang-2 administration led to increased production of catabolic
      proteinases and loss of aggrecan and collagen II in degenerative NP cell
      cultures, which was mediated by the NF-kappaB signaling pathway. Elevated Ang-2
      levels also increased interleukin-1beta expression in degenerative NP cells. We
      conclude that the release of Ang-2 aggravates NP cell degradation and plays an
      important role in IDD. Ang-2 may thus constitute a novel therapeutic target for
      the treatment of IVD.

PMID- 29568931
TI  - miR-590-3p mediates melatonin-induced cell apoptosis by targeting septin 7 in the
      human osteoblast cell line hFOB 1.19.
AB  - The present study aimed to investigate the association between septin 7 (SEPT7)
      and melatonin-induced apoptosis in the human fetal osteoblastic cell line hFOB
      1.19. MicroRNA (miR)-590-3p was identified by identifying overlapping miRNAs that
      target SEPT7, across different databases (miRDB, DIANA and Targetscan). Apoptosis
      was assessed via flow cytometric analysis. Small interfering RNA of SEPT7 and a
      miR-590-3p inhibitor were used for gene silencing and the efficiency was assessed
      by reverse transcription-quantitative polymerase chain reaction. Western blotting
      was used to measure the expression of proteins associated with pathways mediating
      endoplasmic reticulum stress and melatonin-induced apoptosis. The present study
      identified that SEPT7 was a potential target of miR-590-3p and demonstrated that
      SEPT7 is associated with mediating the pro-apoptotic effect of miR-590-3p in
      human osteoblast cell line hFOB 1.19. High concentrations of melatonin may result
      in the inhibition of miR-590-3p expression, leading to the upregulation of target
      genes that promote apoptosis.

PMID- 29568932
TI  - Lemongrass essential oil and citral inhibit Src/Stat3 activity and suppress the
      proliferation/survival of small-cell lung cancer cells, alone or in combination
      with chemotherapeutic agents.
AB  - Small-cell lung cancer (SCLC) is intractable due to its high propensity for
      relapse. Novel agents are thus needed for SCLC treatment. Lemongrass essential
      oil (LG-EO) and its major constituent, citral, have been reported to inhibit the
      proliferation and survival of several types of cancer cells. However, the precise
      mechanisms through which LG-EO and citral exert their effects on SCLC cells have
      not been fully elucidated. SCLC cells express Src and have high levels of Src
      tyrosine kinase (Src-TK) activity. In most SCLC cell lines, constitutive
      phosphorylation of Stat3(Y705), which is essential for its activation, has been
      detected. Src-TK can phosphorylate Stat3(Y705), and activated Stat3 promotes the
      expression of the anti-apoptotic factors Bcl-xL and Mcl-1. In the present study,
      LG-EO and citral prevented Src-TK from phosphorylating Stat3(Y705), resulting in
      decreased Bcl-xL and Mcl-1 expression, in turn suppressing the
      proliferation/survival of SCLC cells. To confirm these findings, the wild-type
      src gene was transfected into the LU135 SCLC cell line (LU135-wt-src), in which
      Src and activated phospho-Stat3(Y705) were overexpressed. The suppression of cell
      proliferation and the induction of apoptosis by treatment with LG-EO or citral
      were significantly attenuated in the LU135-wt-src cells compared with the control
      LU135-mock cells. The signal transducer and activator of transcription 3 (Stat3)
      signaling pathway is also associated with intrinsic drug resistance. LU135-wt-src
      cells were significantly resistant to conventional chemotherapeutic agents
      compared with LU135-mock cells. The combined effects of citral and each
      conventional chemotherapeutic agent on SCLC cells were also evaluated. The
      combination treatment exerted additive or more prominent effects on LU135-wt-src,
      LU165 and MN1112 cells, which are relatively chemoresistant SCLC cells. These
      findings suggest that either LG-EO or citral, alone or in combination with
      chemotherapeutic agents, may be a novel therapeutic option for SCLC patients.

PMID- 29568933
TI  - Effects and mechanism of amyloid beta1-42 on mitochondria in astrocytes.
AB  - Amyloid beta (Abeta)1-42 is strongly associated with Alzheimer's disease (AD).
      The effects of Abeta1-42 on astrocytes remain largely unknown. The present study
      focused on the effects of Abeta1-42 on U87 human glioblastoma cells as astrocytes
      for in vitro investigation and mouse brains for in vivo investigation. The
      mechanism and regulation of mitochondria and cytochrome P450 reductase (CPR) were
      also investigated. As determined by MTT assays, low doses of Abeta1-42 (<1 uM)
      marginally promoted astrocytosis compared with the 0 uM group within 24 h,
      however, after 48 h treatment these doses reduced cellular growth compared with
      the 0 uM group. Furthermore, Abeta1-42 doses >5 uM inhibited the growth of U87
      cells compared with the 0 uM group after 24 and 48 h treatment.
      Immunofluorescence analysis demonstrated that astrocytosis was also observed in
      early stage AD mice compared with wild-type (WT) mice. In addition,
      concentrations of Abeta1-42 were also significantly higher in early stage AD mice
      compared with WT mice, however, the levels were markedly lower compared with
      later stage AD mice, as determined by ELISA. In addition to increased levels of
      Abeta1-42 in mice with later stage AD, reduced astrocyte staining was observed
      compared with WT mice. Western blotting indicated that the effect of Abeta1-42 on
      U87 cell apoptosis may be regulated via Bcl-2 and caspase-3 located in
      mitochondria, whose functions, including adenosine triphosphate generation,
      electron transport chain and mitochondrial membrane potential, were inhibited by
      Abeta1-42. During this process, the expression and activity of cytochrome P450
      reductase was also downregulated. The current study provides novel insight into
      the effects of Abeta1-42 on astrocytes and highlights a potential role for
      astrocytes in the protection against AD.

PMID- 29568934
TI  - Tanshinone-IIA attenuates the deleterious effects of oxidative stress in
      osteoporosis through the NF-kappaB signaling pathway.
AB  - Osteoclasts are responsible for bone resorption caused by bone microstructural
      damage and bone-related disorders. Evidence shows that tanshinone IIA (Tan-IIA),
      a traditional Chinese medicine, is used clinically as a drug for the treatment of
      cardiovascular and cerebrovascular diseases. However, the efficacy and mechanism
      underlying the effect of Tan-IIA on the viability of osteoclasts remain to be
      fully elucidated. The present study investigated the therapeutic effects of Tan
      IIA on osteoblast differentiation and oxidative stress in vitro and in vivo. Cell
      viability was analyzed and oxidative stress was examined in the osteoblasts.
      Wnt1sw/sw mice were used to investigate the therapeutic effects of Tan-IIA on
      spontaneous tibia fractures and severe osteopenia. The bone strength, collagen
      and mineral were examined in the tibia. Osteoblast activity was also analyzed in
      the experimental mice. The Tan-IIA-induced differentiation of osteoclasts and the
      mechanism of action were investigated in osteocytes. The data showed that Tan-IIA
      treatment improved cell viability. The data also demonstrated that Tan-IIA
      decreased the levels of H2O2, accumulation of reactive oxygen species and
      apoptosis of osteoblasts. Tan-IIA inhibited the deleterious outcomes triggered by
      oxidative stress. In addition, Tan-IIA inhibited the activation of nuclear factor
      (NF)-kappaB and its target genes, tumor necrosis factor (TNF)-alpha, inducible
      nitric oxide synthase and cyclooxygenase 2, and increased the levels of TNF
      receptor-associated factor 1 and inhibitor of apoptosis protein-1/2 in the
      osteocytes. Furthermore, it was shown that Tan-IIA reduced the propensity to
      fractures and severe osteopenia in mice with osteoporosis. Tan-IIA also exhibited
      improved bone strength, mineral and collagen in the bone matrix of the
      experimental mice. It was found that the Tan-IIA-mediated benefits on osteoblast
      activity and function were through the NF-kappaB signaling pathway. Taken
      together, the data obtained in the present study suggested that Tan-IIA had
      protective effects against oxidative stress in osteoblastic differentiation in
      mice with osteoporosis by regulating the NF-kappaB signaling pathway.

PMID- 29568935
TI  - Integrated analysis of B-cell and T-cell receptors by high-throughput sequencing
      reveals conserved repertoires in IgA nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated
      with immune dysregulation, and understanding B-/T-cell receptors (BCRs/TCRs) may
      be valuable for the development of specific immunotherapeutic interventions. In
      the present study, B and T cells were isolated from IgAN patients and healthy
      controls, and the composition of the BCR/TCR complementarity-determining region
      (CDR)3 was analyzed by multiplex polymerase chain reaction, high-throughput
      sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3
      clones were expressed at very low frequencies, and the composition of clone types
      in patients with IgAN was skewed; the majority of clones were unique, and only 12
      BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a
      significantly higher frequency in patients with IgAN (P<0.001). There were also
      certain conserved amino acid residues between unique clones or groups, and the
      residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition,
      some VDJ gene recombinations indicated great variation between groups, including
      4 high-frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune
      repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ
      gene recombinations with great variation may be potential therapeutic targets for
      IgAN patients.

PMID- 29568936
TI  - Islet-1 promotes the proliferation and invasion, and inhibits the apoptosis of
      A375 human melanoma cells.
AB  - The aim of this study was to examine the effects of the insulin gene enhancer
      binding protein, islet-1 (ISL1), on the proliferation, invasion and apoptosis of
      the human melanoma cell line, A375. An ISL1 overexpression lentiviral vector was
      constructed and transfected into the A375 cells. The proliferation of the A375
      cells transfected with the ISL1 vector (termed A375/ISL1 cells) was examined by
      MTT assay, flow cytometry and TUNEL assay, and cell invasion was examined by
      Transwell assay. The expression levels of matrix metalloproteinase (MMP)-2 and
      MMP-9 were measured by qPCR and western blot analysis; the expression levels of
      Akt and p-Akt were measured in the cells treated with vascular endothelial growth
      factor (VEGF) and the PI3K/Akt inhibitor, LY294002, by western blot analysis. The
      optical density value of the A375/ISL1 cells was increased after 12 h of culture
      (P<0.001), as shown by MTT assay. The ratio of apoptotic A375/ISL1 cells was
      significantly decreased (P<0.001), as shown by flow cytometry and TUNEL assay. In
      addition, the average penetration rate of the A375/ISL1 cells significantly
      increased (P<0.001), as shown by Transwell assay. The expression levels of MMP-2
      and MMP-9 were significantly increased in the A375/ISL1 cells, as shown by qPCR
      and western blot analysis (P<0.001). Moreover, treatment of the A375/ISL1 cells
      with VEGF for 48 h increased the expression of Akt and p-Akt compared with the
      control cells transfected with A375/green fluorescent protein (GFP) (P<0.05;
      P<0.001, respectively). In addition, in the A375/ISL1 cells treated with the
      LY294002 inhibitor for 24 and 48 h, the level of Akt was also found to increase
      compared to the control A375/GFP cells (P<0.05). On the whole, the findings of
      this study indicate that the overexpression of ISL1 promotes the proliferation
      and invasion, and inhibits the apoptosis of A375 melanoma cells. ISL1 thus plays
      an important role in A375 cell survival, and these effects are possibly mediate
      via the PI3K/Akt signaling pathway.

PMID- 29568937
TI  - Genetic analysis of sick sinus syndrome in a family harboring compound CACNA1C
      and TTN mutations.
AB  - Sick sinus syndrome (SSS) is a sinus node dysfunction characterized by severe
      sinus bradycardia. SSS results in insufficient blood supply to the brain, heart,
      kidneys, and other organs and is associated with the increased risk of sudden
      cardiac death. Bradyarrhythmia appears in the absence of any associated cardiac
      pathology and displays a genetic legacy. The present study identified a family
      with primary manifestation of sinus bradycardia (five individuals) along with
      early repolarization (four individuals) and atrial fibrillation (one individual).
      Targeted exome sequencing was used to screen exons and adjacent splice sites of
      61 inherited arrhythmia-associated genes, to detect pathogenic genes and variant
      sites in the proband. Family members were sequenced by Sanger sequencing and
      protein functions predicted by Polyphen-2 software. A total of three rare
      variants were identified in the family, including two missense variants in
      calcium voltage-gated channel subunit alpha1 C (CACNA1C) (gi:193788541,
      NM_001129843), c.1786G>A (p.V596M) and c.5344G>A (p.A1782T), and one missense
      variant in titin (TTN) c.49415G>A (p.R16472H) (gi:291045222, NM_003319). The
      variants p.V596M and p.R16472H were predicted to be deleterious and resulted in
      alterations in the amino acid type and sequence of the polypeptide chain, which
      may partially or completely inactivate the encoded protein. The comparison of
      literature, gene database, and pedigree phenotype analysis suggests that p.V596M
      or p.R16472H variants are pathogenic. The complex overlapping variants at three
      loci lead to a more severe phenotype in the proband, and may increase the
      susceptibility of individuals to atrial fibrillation. The simultaneous occurrence
      of V596M and R16472H may increase the severity of early repolarization. Various
      family members may have carried heterozygous mutants of p.A1782T and p.R16472H
      due to genetic heterogeneity, however did not exhibit clinical signs of cardiac
      electrophysiological alterations, potentially attributable to the low vagal tone.
      To the best of the author's knowledge, this is the first study to suggest the
      involvement of the novel missense CACNA1C c.1786G>A and TTN c.49415G>A variants
      in the inheritance of symptomatic bradycardia and development of SSS.

PMID- 29568938
TI  - FSCN-1 increases doxorubicin resistance in hepatocellular carcinoma through
      promotion of epithelial-mesenchymal transition.
AB  - Resistance to chemotherapy drugs remains a significant problem for the treatment
      of many types of cancer. Fascin-1 (FSCN-1) is an actin-bundling protein involved
      in the invasion and metastasis of a variety of tumors. However, its involvement
      in drug resistance in hepatocellular carcinoma (HCC) remains unclear. The present
      study aimed to investigate the function of FSCN-1 in HCC resistance to
      doxorubicin (DOX). FSCN-1 expression was increased in DOX-resistant HCC cell
      lines (SNU449 and SNU387) compared with DOX-sensitive cell lines (Huh7 and
      Hep3B). The resistance of HCC cells to DOX was decreased following FSCN-1
      knockdown with small interfering RNA. FSCN-1 knockdown also significantly altered
      the expression of key markers of epithelial-mesenchymal transition (EMT).
      Notably, vimentin expression was reduced and epithelial-cadherin expression was
      increased. Furthermore, when EMT was suppressed through knockdown of Twist, an
      essential pathway of DOX-induced EMT, the viability of HCC cells following
      treatment with DOX was not affected by FSCN-1 expression. Furthermore, FSCN-1
      knockdown eliminated hypoxia-induced doxorubicin resistance and EMT. The results
      of the present study indicated that FSCN-1 expression increased DOX resistance in
      HCC cells via the promotion of EMT, and this phenomenon was maintained in a
      hypoxic environment. FSCN-1 potentially represents a novel target to overcome
      resistance to DOX in HCC.

PMID- 29568939
TI  - Puerarin reduces ischemia/reperfusion-induced myocardial injury in diabetic rats
      via upregulation of vascular endothelial growth factor A/angiotensin-1 and
      suppression of apoptosis.
AB  - Puerarin is an active ingredient of pueraria, which has been developed for
      puerarin injections, used in the treatment of cardiovascular diseases including
      arrhythmia, myocardial ischemia and hypertension. However, the molecular
      mechanisms of puerarin on ischemia/reperfusion (I/R)-induced myocardial apoptosis
      in diabetic rats are not fully understood. The present study aimed to investigate
      whether puerarin can attenuate I/R-induced myocardial apoptosis in diabetic rats,
      and to investigate the underlying mechanism. A hemodynamic analyzing system was
      employed to analyze the left ventricular developed pressure (LVDP), the left
      ventricular end-systolic interior dimension (LVIDs) and the left ventricular end
      diastolic interior dimension (LVIDd). ELISA kits were used to analyze
      malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha
      (TNF-alpha) and interleukin (IL)-6 levels, NO production and caspase-3 activity.
      Nuclear factor (NF)-kappaB, ascular endothelial growth factor A (VEGFA),
      angiotensin (Ang)-I, phosphorylated (p)-endothelial nitric oxide synthase protein
      expression was analyzed using western blot analysis. Puerarin significantly
      reduced the myocardial infarct area, and increased left ventricular developed
      pressure in diabetic rats with myocardial I/R. Oxidative stress, inflammation and
      nuclear factor-kappaB protein expression were significantly reduced by puerarin.
      Furthermore, puerarin activated the protein expression levels of VEGFA and Ang-I,
      and increased nitric oxide production, phosphorylated-endothelial nitric oxide
      synthase protein expression and caspase-3 activity. These results demonstrated
      that the myocardial protective effect of puerarin serves to reduce myocardial I/R
      injury, via upregulation of VEGFA/Ang-1 and suppression of apoptosis, in diabetic
      rats with myocardial I/R.

PMID- 29568940
TI  - Ameliorative effect of nicergoline on cognitive function through the PI3K/AKT
      signaling pathway in mouse models of Alzheimer's disease.
AB  - Alzheimer's disease is one of the most common age-associated diseases that
      frequently leads to memory disorders, cognitive decline and dementia. Evidence
      suggests that nicergoline serves an important role in the apoptosis of
      hippocampal cells, memory recovery, cognitive function and neuronal survival.
      However, the signaling pathway affected by nicergoline treatment remains to be
      elucidated. The purpose of the present study was to investigate the role of
      nicergoline in the cognitive competence of a mouse model of Alzheimer's disease.
      The apoptosis rates of hippocampal cells were studied in mice with Alzheimer's
      disease treated with nicergoline compared with the negative control. Apoptosis
      associated gene expression levels in hippocampal cells, and hippocampus area,
      were analyzed in the experimental mice. Visual attention and inhibitory control
      were assessed and neural counting was performed in brain regions of interest. The
      phosphatidylinositol 3-kinase (PI3K)/RAC-alpha serine/threonine-protein kinase
      (AKT) signaling pathway was additionally analyzed in hippocampal cells following
      treatment with nicergoline. The results of the present study demonstrated that
      nicergoline ameliorated apoptosis in hippocampal cells and hippocampus tissue in
      3xTg-AD mice with Alzheimer's disease. The data indicated that apoptosis
      associated genes, including caspase-3, BCL2 associated X, BH3 interacting domain
      death agonist and caspase-9, were downregulated in hippocampal cells isolated
      from nicergoline-treated experimental mice. In addition, the expression levels of
      inflammatory factors, in addition to oxidative stress, were decreased in
      hippocampal cells treated with nicergoline. Additionally, amyloid precursor
      protein accumulation was cleared in the hippocampal area in nicergoline-treated
      mice. Nicergoline inhibited neuronal loss and prevented cognitive impairment
      through the restoration of learning/memory ability. It was additionally
      demonstrated in the present study that nicergoline improved motor attention
      impairment and cognitive competence in hippocampal cells by acting on the
      PI3K/AKT signaling pathway. Therefore, memory recovery, cognitive function and
      neuronal survival were repaired by nicergoline via inhibition of the PI3K/AKT
      signaling pathway, suggesting that nicergoline may be an efficient drug for the
      clinical treatment of patients with Alzheimer's disease.

PMID- 29568941
TI  - Bradykinin potentially stimulates cell proliferation in rabbit corneal
      endothelial cells through the ZO-1/ZONAB pathway.
AB  - Bradykinin (BK) has been demonstrated to induce proliferation in several types of
      cell in ex vivo corneas. However, the mechanisms underlying the action of BK on
      corneal endothelial cells (CECs) remain largely unknown. The present study aimed
      to investigate the effect of BK on rabbit corneal endothelial cell (RCEC)
      proliferation, and assess the involvement of the zonula occludens-1(ZO-1)/ZO
      1associated nucleic acid binding protein (ZONAB) pathway. Cell proliferation and
      cell cycle distribution was analyzed following treatment with BK (0.01, 0.1,1.0
      or 10.0 uM) for the indicated time intervals (24, 48, 72 and 96 h), or following
      BK treatment combined with transfection of ZONAB-small interfering (si)RNA for 72
      h. In addition, the expression of tight junction ZO-1, nuclear ZONAB,
      proliferating cell nuclear antigen(PCNA) and cyclin D1 were evaluated using
      western blotting or immunofluorescence. BK treatment was demonstrated to induce
      time- and concentration-dependent cell proliferation and cell cycle progression,
      along with the upregulation of tight junction ZO-1 and nuclear ZONAB, as well as
      PCNA and cyclin D1 protein expression. Furthermore, knockdown with ZONAB-siRNA
      inhibited cell proliferation, induced cell cycle arrest and downregulated PCNA
      and cyclin D1 protein expression. ZONAB knockdown therefore successfully reversed
      the increase in proliferation induced by BK treatment. Taken together, these
      results suggested that BK stimulated RCEC proliferation, potentially via the ZO
      1/ZONAB pathway. The signaling paradigm disclosed in the present study
      potentially serves as an important therapeutic target for cornea regeneration and
      transplantation.

PMID- 29568942
TI  - Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis
      of myocardial cells through activation of the JAK2/STAT3 signaling pathway.
AB  - Myocardial cell apoptosis mediated by oxidative stress has previously been
      identified as a key process in ischemic heart disease. Secoisolariciresinol
      diglucoside (SDG), a polyphenolic plant lignan primarily found in flaxseed, has
      been demonstrated to effectively protect myocardial cells from apoptosis. In the
      present study, the role of the Janus kinase 2 (JAK2)/signal transducer and
      activator of transcription 3 (STAT3) was investigated in mediating the protective
      effect of SDG. Findings of the present study revealed that treatment with H2O2
      reduced cell viability and induced apoptosis in H9C2 rat cardiomyocytes. However,
      SDG was able to reduce the effect of H2O2 in a dose-dependent manner. H2O2
      reduced the expression level of phosphorylated STAT3 and inhibited the levels of
      B-cell lymphoma-extra-large and induced myeloid leukemia cell differentiation
      protein, which are the STAT3 target genes. Conversely, SDG rescued
      phosphorylation of STAT3 and increased the levels of STAT3 target genes.
      Treatment with SDG alone led to a dose-dependent increased phosphorylation of
      JAK2 and STAT3, without activating Src. Furthermore, the anti-apoptotic effects
      of SDG were partially abolished by a JAK2/STAT3 inhibitor. In addition, molecular
      docking revealed that SDG may bind to the protein kinase domain of JAK2, at a
      binding energy of -8.258 kcal/mol. Molecular dynamics simulations revealed that
      JAK2-SDG binding was stable. In conclusion, activation of the JAK2/STAT3
      signaling pathway contributed to the anti-apoptotic activity of SDG, which may be
      a potential JAK2 activator.

PMID- 29568943
TI  - Identification of aberrantly expressed long non-coding RNAs in postmenopausal
      osteoporosis.
AB  - Postmenopausal osteoporosis (PMOP) is a common skeletal disorder in
      postmenopausal women. The present study aimed to identify the key long non-coding
      RNAs (lncRNAs) in PMOP through RNA sequencing. RNA sequencing was performed to
      obtain the expression profile of lncRNAs and mRNAs in blood samples of patients
      with PMOP and normal controls (NCs). Following the identification of
      differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs
      (DElncRNAs), the DElncRNA-DEmRNA co-expression network was constructed. A search
      was performed for the DEGs transcribed within a 100-kb window upstream or
      downstream of DElncRNAs, which served as nearby DEmRNAs of DElncRNAs. Functional
      annotation of the DEmRNAs co-expressed with DElncRNAs was performed. The GSE56815
      dataset was used to verify the expression of selected DEmRNAs and DElncRNAs.
      Three blood samples from patients with PMOP and two blood samples from NCs were
      used for RNA sequencing. Compared with the NC group, a total of 185 DEmRNAs and
      51 DElncRNAs were obtained in PMOP. A total of 3,057 co-expression DElncRNA
      DEmRNA pairs and 97 DElncRNA-nearby DEmRNA pairs were obtained. Six DEmRNAs
      [diacylglycerol O-acyltransferase 2, potassium voltage-gated channel subfamily S
      member 1, peptidase inhibitor 3, secretory leukocyte peptidase inhibitor,
      galectin-related protein and alkaline phosphatase, liver/bone/kidney (ALPL)] were
      nearby co-expressed genes of four DElncRNAs, including LOC105376834,
      LOC101929866, LOC105374771 and LOC100506113. Three PMOP-associated DEmRNAs,
      including ALPL, suppressor of cytokine signaling 3 and adrenomedullin, were co
      expressed with the hub DElncRNAs (LINC00963, LOC105378415, LOC105377067, HCG27,
      LOC101928143 and LINC01094) of the positively and negatively co-expressed
      DElncRNA-DEmRNA interaction network. The expression of selected DEmRNAs and
      DElncRNAs was consistent with the RNA-sequencing results. In conclusion, the
      present study identified the key DEmRNAs and DElncRNAs in PMOP, which may provide
      clues for understanding the mechanism and developing novel biomarkers for PMOP.

PMID- 29568945
TI  - Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion
      in an exosome-dependent manner and correlates with poor prognosis.
AB  - Pancreatic cancer is one of the most lethal types of cancer; owing to low early
      detection rates and high metastasis rates, it is associated with an extremely
      poor prognosis. Therefore, a better understanding of the molecular mechanisms
      that underlie its metastasis and the identification of potential prognostic
      biomarkers are urgently required. Although high expression levels of asparaginyl
      endopeptidase (AEP) have been detected in various types of solid tumor, the
      expression and functions of AEP in pancreatic carcinomas have yet to be
      determined. The present study aimed to examine the putative functions of AEP in
      pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly
      expressed in pancreatic cancer tissues compared with adjacent normal tissues.
      Patients with high AEP expression exhibited a significantly shorter overall
      survival time. Results from multivariate Cox regression analysis revealed that
      AEP was an independent prognostic factor for overall survival. Gain- and loss-of
      function experiments demonstrated that knockdown of AEP expression significantly
      reduced the invasive ability of pancreatic cancer cells, whereas overexpression
      of AEP increased the invasive ability. In addition, AEP was detected in exosomes
      that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs)
      and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay
      revealed that exosomes enriched with AEP were able to enhance the invasive
      ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive
      ability. Furthermore, results from the present study suggested that AEP may be
      crucial for activation of the phosphoinositide 3-kinase/RAC-alpha
      serine/threonine-protein kinase signaling pathway in PDAC cells. The present
      study data indicated that high AEP expression may be important for pancreatic
      carcinoma progression in an exosome-dependent manner, and that AEP may be an
      independent indicator of poor prognosis in patients with PDAC and may be a novel
      prognostic biomarker or therapeutic target in pancreatic carcinoma.

PMID- 29568944
TI  - PEDF regulates lipid metabolism and reduces apoptosis in hypoxic H9c2 cells by
      inducing autophagy related 5-mediated autophagy via PEDF-R.
AB  - Pigment epithelial-derived factor (PEDF) is a multifunctional secreted
      glycoprotein, which exerts a variety of physiological activities. PEDF may
      protect against hypoxia-induced cell death associated with its antioxidative
      effects and p53 mitochondrial translocation in cultured cardiomyocytes and H9c2
      cells. Additionally, previous studies have suggested that autophagy is an
      important cell survival mechanism. However, the effect of PEDF on autophagy and
      the associated pathway in hypoxic H9c2 cells has not been fully established.
      Autophagy has been reported to regulate lipid metabolism; however, little is
      known about whether PEDF is able to regulate lipid metabolism by promoting
      autophagy. In the present study, western blotting results revealed that PEDF
      increased the level of microtubule-associated protein 1A/1B-light chain 3 (LC3)
      II. Transmission electron microscopy (TEM) and LC3 fluorescence demonstrated that
      PEDF increased the number of autophagosomes. PEDF also increased the viability of
      hypoxic H9c2 cells and decreased the level of cleaved caspase-3 protein, as
      evidenced by CCK-8 assays and western blotting, respectively. TEM and a
      triglyceride assay kit demonstrated that PEDF-induced autophagy may stimulate
      lipid degradation. Western blotting results revealed a novel mechanism underlying
      PEDF-induced H9c2 cell autophagy via the PEDF-R-mediated Atg5 pathway under
      hypoxic conditions. Furthermore, the results also suggest that PEDF-induced
      autophagy may stimulate lipid degradation. The survival function of autophagy
      suggests that modulation of PEDF-induced autophagy may be used as a therapeutic
      strategy to protect cells against lipid-associated metabolic diseases.

PMID- 29568946
TI  - Gefitinib inhibits malignant melanoma cells through the VEGF/AKT signaling
      pathway.
AB  - Malignant melanoma (MM) is caused by melanophore cancerization in tissue
      pigmentation regions, leading to skin, mucous membrane, eye and central nervous
      system carcinogenesis. The incidence of MM has increased in previous years, and
      it has become the primary cause of skin cancer-associated mortality in developed
      countries. MM is characterized as highly malignant and readily metastasized, and
      has a poor prognosis. Targeting angiogenesis is an important method for MM
      treatment. As an important proangiogenic factor in tumor growth and metastasis,
      vascular endothelial growth factor (VEGF) can promote neovascularization and
      increase vascular permeability. Gefitinib is a novel drug targeting VEGF. The
      effect and mechanism of gefitinib on MM remain to be elucidated, and were
      investigated in the present study. The A375 MM cell line was used in the present
      study; it was cultured in vitro and divided into gefitinib groups (5 and 10 uM)
      and a control group. Cell proliferation was measured using an MTT assay and the
      activity of caspase-3 was assessed using a kit. Cell invasive ability was
      determined using a Transwell chamber. The mRNA and protein expression levels of
      VEGF and AKT were detected using reverse transcription-quantitative polymerase
      chain reaction and western blot analyses. Gefitinib significantly inhibited MM
      cell proliferation, enhanced the activity of caspase 3 and suppressed tumor cell
      invasion (P<0.05). In addition, gefitinib significantly downregulated the mRNA
      and protein expression levels of VEGF and AKT, and these changes were dose
      dependent (P<0.05). Taken together, gefitinib suppressed MM cell proliferation
      and invasion in vitro by regulating the VEGF/AKT signaling pathway.

PMID- 29568948
TI  - Overexpression of collagen type V alpha1 chain in human breast invasive ductal
      carcinoma is mediated by TGF-beta1.
AB  - Collagen type V alpha1 chain (COL5A1) is a minor fibrillar collagen in mammals
      that co-polymerizes with type I collagen to adjust the diameter of collagen
      molecules. However, the function of COL5A1 in invasive ductal carcinoma (IDC) of
      the human breast remains unknown. In the present study, our group examined the
      expression of COL5A1 in IDC compared with its adjacent normal tissue and
      fibroadenoma of the breast. COL5A1 was revealed to be overexpressed in IDC
      compared with benign tumor and adjacent normal control tissues, and was
      associated with the expression of estrogen receptor and progesterone receptor. No
      association between COL5A1 expression and tumor size, lymph node metastasis,
      clinical stage, age, or Her2 expression was identified. High expression of COL5A1
      mRNA was associated with distant metastasis free survival in patients with breast
      cancer. Knockdown of COL5A1 led to a decrease of cell viability, as detected by
      the WST-1 assay, and an inhibition of migration and invasion, as detected by
      wound healing and Transwell assays, respectively, in the breast cancer cell line
      MCF-7. The expression of COL5A1 in MCF-7 cells was downregulated by transforming
      growth factor (TGF)-beta1, which was abolished in the presence of SB-431542, an
      inhibitor of TGF-beta type I receptor. In conclusion, these data indicated that
      COL5A1 is overexpressed in IDC and regulated by TGF-beta1, suggesting that an
      increase of COL5A1 reflects tumor progression and may serve as a novel biomarker
      and therapeutic target for the treatment of breast IDC.

PMID- 29568947
TI  - Low molecular weight fucoidan attenuates experimental abdominal aortic aneurysm
      through interfering the leukocyte-endothelial cells interaction.
AB  - Low molecular weight fucoidan (LMWF) is a sulfated polysaccharide extracted from
      Saccharina Japonica that presents high affinity for P-selectin and abolish
      selectin-dependent recruitment of leukocytes. We hypothesized that dietary intake
      of LMWF, as a competitive binding agent of P-selectin, could limit the
      inflammatory infiltration and aneurysmal growth in an Angiotensin II-induced
      abdominal aortic aneurysm (AAA) mouse model. The Gene Expression Omnibus database
      was used for gene expressions and gene set enrichment analysis. Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment analysis showed that focal
      adhesion was involved in the development of AAA. However, dietary intake of LMWF
      could limit the enlargement of AAA, decreasing maximal aortic diameter and
      preserving elastin lamellae. Although LMWF did not decrease the circulatory
      monocytes count and lower the expression of P-selectin in endothelium, it reduced
      macrophages infiltration in media and adventitia. Furthermore, matrix
      metalloproteinase expression was markedly downregulated, accompanied with reduced
      expression of inflammatory mediators, including interleukin 1beta, tumor necrosis
      factor-alpha and monocyte chemotactic protein-1. The present study revealed a
      novel target for the treatment of AAA and the anti-inflammatory effects of LMWF.

PMID- 29568949
TI  - Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing
      intracellular reactive oxygen species.
AB  - Pyrroloquinoline quinone (PQQ) has been reported to contribute to cancer cell
      apoptosis and death; however, little is known of its underlying mechanisms. The
      present study was designed to investigate the role of PQQ in chondrosarcoma cell
      apoptosis and the underlying mechanism. A cell cytotoxicity assay was used to
      detect cell death; flow cytometry analysis was also performed to determine cell
      apoptosis and intracellular reactive oxygen species (ROS). Biochemical methods
      were employed to detect the activity and the expression of superoxide dismutase
      (SOD)1, SOD2 and glutathione. The present study also examined the effect on
      tumorigenesis in vivo. The results demonstrated that the apoptosis of SW1353
      cells induced by PQQ increased in a concentration- and time-dependent manner,
      which may be attributable to the accumulation of intracellular ROS. In the in
      vivo experiments, PQQ inhibited proliferation and promoted apoptosis, increased
      ROS levels and caused DNA damage in transplanted cells. Taken together, the
      findings of the present study confirmed that PQQ induced apoptosis in human
      chondrosarcoma SW1353 cells and transplanted cells, by increasing intracellular
      ROS and reducing the ability of scavenging oxygen free radicals.

PMID- 29568950
TI  - Genistein inhibits invasion and migration of colon cancer cells by recovering
      WIF1 expression.
AB  - Colon cancer is characterized by invasion and migration. DNA methylation of CpG
      islands in tumor suppressor genes is considered to be an epigenetic mechanism
      underlying cancer development. Epigenetic silencing of a gene may be reversed by
      drugs, including genistein. The present study aimed to determine the effect of
      genistein on Wnt inhibitory factor 1 (WIF1) and invasion, and migration of colon
      cancer cells. The viability of HT29 colon cancer cells was suppressed by
      genistein in a dose dependent manner. Following 72 h of treatment with 10, 20 and
      60 umol/l genistein, increased demethylation of WIF1 was induced in a dose
      dependent manner. Additionally, the invasive/migratory abilities of cells treated
      with genistein decreased in a dose-dependent manner. Reverse transcription
      quantitative polymerase chain reaction and western blot analyses were performed
      to identify the mRNA and protein expression levels of invasion/migration
      associated factors. Following treatment with genistein, matrix metalloproteinase
      (MMP) 2 and MMP9 expression levels decreased, whereas the expression of
      metalloproteinase inhibitor 1 and E-cadherin increased significantly. In
      addition, the expression levels of proto-oncogene Wnt-1 (Wnt-1)/beta-catenin
      pathway-associated factors, beta-catenin, c-Myc proto-oncogene protein and cyclin
      D1 decreased in a dose-dependent manner following treatment with genistein. The
      invasive/migratory abilities of cells transfected with WIF1-small interfering
      (si) RNA, and those transfected with WIF1-siRNA and treated with genistein,
      increased notably compared with the control group. The present study demonstrated
      that genistein was able to inhibit the cell invasion and migration of colon
      cancer cells by inducing demethylation, and recovering the activity of WIF1 by
      altering the expression of invasion-associated factors, and components of the Wnt
      signaling pathway.

PMID- 29568951
TI  - Effect of liposome-mediated HSP27 transfection on collagen synthesis in alveolar
      type II epithelial cells.
AB  - To investigate the effect of liposome Lipofectamine(r) 2000-mediated HSP27
      plasmid transfection in A549 human alveolar type II epithelial cell line on
      collagen synthesis during transforming growth factor-beta1 (TGF-beta1)-induced
      type II epithelial cell transition to myofibroblasts. Cells were transfected with
      varying ratios of the Lipofectamine(r) 2000-mediated heat shock protein 27
      (HSP27) plasmid and the transfection efficiency was determined using flow
      cytometry. The maximum transfection efficacy was confirmed by laser confocal
      microscopy. HSP gene expression and the most efficient HSP27 plasmid were
      determined using reverse transcription-quantitative polymerase chain reaction.
      Western blot analysis was used to examine HSP27 and collagen expression levels.
      With a transfection efficiency of 83%, the 8 ug:20 ul ratio of liposome: Plasmid
      had the highest transfection levels. Among the four different interference
      sequences in the HSP27 plasmid, the D sequence had the highest interference
      effect with 70% silencing of the HSP27 gene. The expression of type I and III
      collagen in TGF-beta1-induced transition of A549 human alveolar type II
      epithelial cell line to myofibroblasts was significantly downregulated by the
      successful transfection with HSP27-interfering plasmid. The expression of type I
      and III collagen in the TGF-beta1-induced transition of A549 cells to
      myofibroblasts was significantly downregulated by transfection of A549 cells with
      HSP27 plasmid D-interfering sequence and optimal ratio of Lipofectamine(r) 2000
      and HSP27 plasmid.

PMID- 29568952
TI  - Whole exome sequencing identifies novel candidate mutations in a Chinese family
      with left ventricular noncompaction.
AB  - Left ventricular noncompaction (LVNC) is an inherited cardiomyopathy involving
      numerous genes. To identify novel candidate causal mutations, a whole exome
      sequencing study was performed on a Chinese LVNC family. Exons of the most
      prevalent pathogenic genes of LVNC (myosin heavy chain 7 and actin, alpha-cardiac
      muscle 1) were sequenced, although no mutations were identified. Following this,
      Burrows-Wheeler Aligner, PICARD and Genome Analysis Toolkit (v.2.8) were used to
      analyze the exome sequencing data. Non-silent single nucleotide variants (SNVs)
      that were identified in patients with LVNC, although not in the healthy
      individual, were investigated further using SNV prioritization via the
      integration of genomic data (SPRING) based on P-values. Co-expressed gene
      enrichment analysis was performed using Genotype Tissue Expression (GTEx) data in
      order to investigate the potential roles of the genes containing SNVs in the
      myocardium. In the Chinese LVNC family, seven novel SNVs were identified that
      were only present in patients with LVNC and annotated by SPRING with P<0.05.
      Among these SNVs, hemicentin 1 [c. thymine (T) 9776 cytosine (C)], tolloid like 2
      [c. cytosine (C) 2615 thymine (T)], fms related tyrosine kinase 3 [c. guanine (G)
      976 adenine (A)] and nucleotide binding protein like [c. guanine (G) 91 thymine
      (T)] were located in conserved regions and annotated as deleterious by PolyPhen2,
      LRT and MutationTaster database analyses. Based on GTEx data, it was revealed
      that NUBPL was co-expressed with almost all previously established LVNC
      pathogenic genes. Furthermore, the results of the present study demonstrated that
      genes co-expressed with NUBPL were additionally enriched in the Notch signaling
      pathway. In addition, the results revealed numerous novel mutations that may be
      causal SNVs for the development of LVNC in the family involved in the present
      study.

PMID- 29568953
TI  - Comparison of mouse brown and white adipose-derived stem cell differentiation
      into pacemaker-like cells induced by TBX18 transduction.
AB  - The present study aimed to compare brown adipose-derived stem cell (BASC) and
      white adipose-derived stem cell (WASC) differentiation into pacemaker-like cells
      following T-box (TBX)18 transduction. Mouse BASCs and WASCs were induced to
      differentiate into pacemaker-like cells by adenovirus-TBX18 transduction in
      vitro. The transduction rate was determined by fluorescence microscopy and cell
      ultrastructural changes were observed by transmission electron microscopy at 48 h
      post-transduction. The mRNA and protein expression of pacemaker cell-associated
      markers, including TBX18, TBX3, sarcomeric alpha-actinin (Sr) and
      hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), were
      detected by reverse transcription-quantitative polymerase chain reaction,
      immunofluorescence staining and western blot analysis. The results demonstrated
      that no significant difference was observed in the transduction rate between
      BASCs and WASCs. The ultrastructure of BASCs was observed to be more complex than
      that of WASCs, indicating that BASCs may possess a better structural foundation
      to differentiate into pacemaker-like cells. TBX18, TBX3, Sr and HCN4 mRNA and
      protein expression in differentiated stem cells was significantly increased
      compared with the respective control groups. Furthermore, the expression levels
      were significantly higher in TBX18-BASCs compared with TBX18-WASCs. In
      conclusion, TBX18 gene transduction may facilitate the differentiation of BASCs
      and WASCs into pacemaker-like myocardial cells, and BASCs may have a higher
      capacity than WASCs for this differentiation. TBX18 gene may therefore act as an
      efficient candidate in cell transplantation therapy for diseases and for future
      research into the cardiovascular system.

PMID- 29568954
TI  - Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration
      in a rat model of diabetic kidney disease.
AB  - Renal interstitial fibrosis is a final pathway that is observed in various types
      of kidney diseases, including diabetic kidney disease (DKD). The present study
      investigated the effect of tranilast on renal interstitial fibrosis and the
      association between its role and mast cell infiltration in a rat model of DKD. A
      total of 30 healthy 6-week-old male Sprague-Dawley rats were randomly divided
      into the following four groups: Normal control group; DKD model group; low-dose
      tranilast group (200 mg/kg/day); and high-dose tranilast group (400 mg/kg/day).
      The morphological alterations of tubulointerstitial fibrosis were evaluated by
      Masson's trichrome staining, while mast cell infiltration into the renal tubular
      interstitium was measured by toluidine blue staining and complement C3a receptor
      1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN),
      collagen I (Col-I), stem cell factor (SCF) and proto-oncogene c-kit (c-kit) was
      detected by IHC, western blotting and reverse transcription-quantitative
      polymerase chain reaction. The results demonstrated that tubulointerstitial
      fibrosis and mast cell infiltration were observed in DKD model rats, and this was
      improved dose-dependently in the tranilast treatment groups. The expression of
      FN, Col-I, SCF and c-kit mRNA and protein was upregulated in the
      tubulointerstitium of DKD model rats compared with the normal control rats, and
      tranilast inhibited the upregulated expression of these markers. Furthermore, the
      degree of SCF and c-kit expression demonstrated a significant positive
      correlation with C3aR-positive mast cells and the markers of renal interstitial
      fibrosis. The results of the present study indicate that mast cell infiltration
      may promote renal interstitial fibrosis via the SCF/c-kit signaling pathway.
      Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell
      infiltration mediated through the SCF/c-kit signaling pathway.

PMID- 29568955
TI  - hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic
      effects through suppression of TGF-beta signaling.
AB  - GV1001 is a 16-amino acid peptide derived from the human telomerase reverse
      transcriptase (hTERT) protein (616-626; EARPALLTSRLRFIPK), which lies within the
      reverse transcriptase domain. Originally developed as an anticancer vaccine,
      GV1001 demonstrates diverse cellular effects, including anti-inflammatory, tumor
      suppressive and antiviral effects. In the present study, the radioprotective and
      antifibrotic effects of GV1001 were demonstrated through suppressing transforming
      growth factor-beta (TGF-beta) signaling. Proliferating human keratinocytes
      underwent premature senescence upon exposure to ionizing radiation (IR), however,
      treatment of cells with GV1001 allowed the cells to proliferate and showed a
      reduction in senescent phenotype. GV1001 treatment notably increased the levels
      of Grainyhead-like 2 and phosphorylated (p-)Akt (Ser473), and reduced the
      activation of p53 and the level of p21/WAF1 in irradiated keratinocytes. It also
      markedly suppressed the level of TGF-beta signaling molecules, including p-small
      mothers against decapentaplegic (Smad)2/3 and Smad4, and TGF-beta target genes,
      including zinc finger E-box binding homeobox 1, fibronectin, N-cadharin and
      Snail, in irradiated keratinocytes. Furthermore, GV1001 suppressed TGF-beta
      signaling in primary human fibroblasts and inhibited myofibroblast
      differentiation. Chromatin immunoprecipitation revealed that GV1001 suppressed
      the binding of Smad2 on the promoter regions of collagen type III alpha1 chain
      (Col3a1) and Col1a1. In a dermal fibrosis model in vivo, GV1001 treatment notably
      reduced the thickness of fibrotic lesions and the synthesis of Col3a1. These data
      indicated that GV1001 ameliorated the IR-induced senescence phenotype and tissue
      fibrosis by inhibiting TGF-beta signaling and may have therapeutic effects on
      radiation-induced tissue damage.

PMID- 29568957
TI  - [Retracted] Rivaroxaban attenuates thrombosis by targeting the NF-kappaB
      signaling pathway in a rat model of deep venous thrombus.
AB  - Following the publication of this article, an interested reader made us aware
      that the authors of the above paper had misappropriated certain of the data that
      had been published previously in three different papers. Specifically, Fig. 2A, B
      and G in the above paper appeared to be derived from Figs. 2A, 3 and 1A,
      respectively, of the paper by CM Ripplinger, CW Kessinger, C Li, JW Kim, JR
      McCarthy, R Weissleder, PK Henke, CP Lin and FA Jaffer (Arterioscler Thromb Vasc
      Biol 32: 2616-2624, 2012). Figs. 2E, F, H, I and J in the above paper appeared to
      be derived from Figs. 1, 2A, 2D, 5E and 3F, respectively, of the paper by ML von
      Bruhl, K Stark, A Steinhart, S Chandraratne, I Konrad, M Lorenz, A Khandoga, A
      Tirniceriu, R Coletti, M Kollnberger, et al (J Exp Med 209: 819-835, 2012). Fig.
      6C in the above paper appeared to be derived from Fig. 2D in the paper by CW
      Kessinger, JW Kim, PK Henke, B Thompson, JR McCarthy, T Hara, M Sillesen, RJ
      Margey, P Libby, R Weissleder, et al [PLoS One 10(2): e0116621, 2015], and Fig.
      6H in the above paper appeared to be derived from Fig. 4 in the paper by von
      Bruhl et al. Following an internal enquiry, the Editor of International Journal
      of Molecular Medicine has determined that the claim should be upheld; therefore,
      the Editorial Board has decided that the article should be retracted. All efforts
      were made to contact the corresponding author of the above article. The Editor
      apologizes to the readership of the Journal for any inconvenience caused. [the
      original article was published in the International Journal of Molecular Medicine
      40: 1869-1880, 2017; DOI: 10.3892/ijmm.2017.3166].

PMID- 29568956
TI  - Genome-wide transcriptional analysis of BRD4-regulated genes and pathways in
      human glioma U251 cells.
AB  - Bromodomain containing 4 (BRD4), a member of the bromodomain and extra-terminal
      family, has become a promising drug target for numerous types of cancer. BRD4 has
      been reported to be deregulated in gliomas; however, the precise molecular
      pathways regulated by BRD4 remained elusive. In the present study, BRD4
      expression was silenced in the glioma cell line U251 and the results demonstrated
      that BRD4 knockdown attenuated cell proliferation and promoted cell apoptosis. A
      genome-wide analysis of BRD4-regulated transcripts in U251 cells was performed
      using microarray to reveal the possible molecular mechanism. A total of 3,529
      differentially expressed genes were identified; 1,648 of these genes were
      upregulated and 1,881 were downregulated. The results of the gene ontology
      analysis revealed that these genes were mainly involved in membrane organization,
      mitotic cell cycle, cell division and DNA replication. Pathway analysis revealed
      that the pathways altered following BRD4 knockdown included multiple cellular
      processes, such as cell cycle and apoptosis. Candidate genes were identified
      through global signal transduction network analysis and were validated using
      reverse transcription-quantitative polymerase chain reaction and western blot
      analyses. The results demonstrated that BRD4 knockdown decreased the expression
      of KRAS proto-oncogene GTPase (KRAS). Downregulated KRAS expression in U251 cells
      restrained cell proliferation and promoted cell apoptosis, suggesting that the
      effect of BRD4 on glioma cells might occur through the Ras pathway. In
      conclusion, the present results confirmed the role of BRD4 in glioma and provided
      information for further exploration of the molecular mechanism of BRD4 in glioma
      development and progression.

PMID- 29568958
TI  - Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis
      through mitochondria- and ER-medicated oxidative stress pathways.
AB  - Dexmedetomidine (DEX), an alpha2 adrenoceptor agonist, has sedative and analgesic
      properties and myocardial protective effects. However, the mechanism underlying
      the protective effects of DEX on the myocardium remain unclear. The present study
      aimed to determine whether DEX serves an important role on cardioprotection
      through the endoplasmic reticulum (ER)- and mitochondria-mediated apoptosis
      signaling pathways. Neonatal rat cardiomyocytes (NRCMs) were cultured and divided
      four groups: i) Normal culture medium with 10% fetal bovine serum (control
      group); ii) H2O2 at 500 uM (H2O2 group); iii) DEX at 5 uM (DEX group); and iv)
      H2O2 plus DEX (H2O2 + DEX group). The levels of apoptosis and oxidative stress of
      NRCMs were investigated by ELISA, western blotting, flow cytometry and cell
      immunofluorescence. DEX significantly suppressed H2O2-induced apoptosis, and
      increased activity of caspases 3, 8 and 9 of NRCMs. DEX inhibited mitochondria
      mediated oxidative stress and apoptosis, as evidenced by decreased levels of
      reactive oxygen species and lactic dehydrogenase, alleviated mitochondrial
      membrane potential depolarization, and increased Bcl-2-associated X protein/B
      cell lymphoma 2 ratio. In addition, DEX decreased the activity of caspase 12, and
      the expression levels of glucose-regulated protein 78 kDa and serine/threonine
      protein kinase/endoribonuclease IRE1, three major signaling molecules involved in
      the ER stress-mediated apoptosis pathway. Preventive treatment with DEX
      alleviates cardiomyocyte against H2O2-induced oxidative stress injury through
      attenuating the mitochondria- and ER-mediated apoptosis pathways.

PMID- 29568959
TI  - Ethoxysanguinarine inhibits viability and induces apoptosis of colorectal cancer
      cells by inhibiting CIP2A.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) an endogenous inhibitor of
      protein phosphatase 2A (PP2A), which can promote proliferation and transformation
      of several cancer types, has been shown to be a target for tumor therapy. The
      present study investigated the effects and underlying mechanisms of action of a
      novel natural compound, ethoxysanguinarine (Eth), on colorectal cancer (CRC)
      cells. MTT assay and flow cytometric assay found that Eth inhibited the viability
      and induced the apoptosis of the CRC cells. The inhibition of viability and
      activation of apoptosis was mediated through the Eth-induced decrease in CIP2A
      expression. Knockdown of CIP2A by RNA interference sensitized, whereas
      overexpression of CIP2A antagonized, Eth-induced viability inhibition and
      apoptosis. Furthermore, western blot analysis suggested that Eth inhibited
      phosphorylation of CIP2A downstream molecule protein kinase B via the activation
      of PP2A. CRC xenograft tests also confirmed the antitumor effect of Eth in vivo.
      These results advance our understanding of Eth-induced viability inhibition and
      apoptosis, implying the requirement for further investigation of Eth as a CIP2A
      inhibitor for cancer therapies.

PMID- 29568960
TI  - Biphasic activation of nuclear factor-kappaB and expression of p65 and c-Rel
      following traumatic neuronal injury.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) has been shown to
      function as a key regulator of cell death or survival in neuronal cells. Previous
      studies indicate that the biphasic activation of NF-kappaB occurs following
      experimental neonatal hypoxia-ischemia and subarachnoid hemorrhage. However, the
      comprehensive understanding of NF-kappaB activity following traumatic brain
      injury (TBI) is incomplete. In the current study, an in vitro model of TBI was
      designed to investigate the NF-kappaB activity and expression of p65 and c-Rel
      subunits following traumatic neuronal injury. Primary cultured neurons were
      assigned to control and transected groups. NF-kappaB activity was detected by
      electrophoretic mobility shift assay. Western blotting and immunofluorescence
      were used to investigate the expression and distribution of p65 and c-Rel.
      Reverse transcription-quantitative polymerase chain reaction was performed to
      assess the downstream genes of NF-kappaB. Lactate dehydrogenase (LDH)
      quantification and trypan blue staining were used to estimate the neuronal
      injury. Double peaks of elevated NF-kappaB activity were observed at 1 and 24 h
      following transection. The expression levels of downstream genes exhibited
      similar changes. The protein levels of p65 also presented double peaks while c
      Rel was elevated significantly in the late stage. The results of the trypan blue
      staining and LDH leakage assays indicated there was no sustained neuronal injury
      during the late peak of NF-kappaB activity. In conclusion, biphasic activation of
      NF-kappaB is induced following experimental traumatic neuronal injury. The
      elevation of p65 and c-Rel levels at different time periods suggests that within
      a single neuron, NF-kappaB may participate in different pathophysiological
      processes.

PMID- 29568961
TI  - Cytoprotective effects of diosmetin against hydrogen peroxide-induced L02 cell
      oxidative damage via activation of the Nrf2-ARE signaling pathway.
AB  - Oxidative stress is considered a crucial mediator in the pathogenesis of various
      liver diseases. The flavone diosmetin has been reported to exhibit antioxidant
      activities; however, the hepatoprotective effects of diosmetin against oxidative
      stress, and the underlying molecular mechanisms, remain unknown. The present
      study aimed to investigate the potential hepatoprotective effects of diosmetin on
      hydrogen peroxide (H2O2)-induced oxidative damage in L02 cells and attempted to
      evaluate the role of the nuclear factor erythroid 2-related factor 2
      (Nrf2)/antioxidant response element pathway in this process. L02 cells were
      divided into groups: Control (DMSO, diosmetin), H2O2, Trolox or tertiary
      butylhydroquinone and diosmetin (different doses). Protective effects in L02
      cells were determined by CCK-8, cell apoptosis and lactate dehydrogenase leakage
      assays. Flow cytometry and inverted fluorescence microscope were used to measure
      the intracellular reactive oxygen species (ROS) and mitochondrial membrane
      potential (MMP). Protein expression levels were of Nrf2, heme oxygenase-1 (HO-1)
      and NAD(P)H quinone oxidoreductase-1 (NQO1) were determined by western blotting
      and mRNA levels were determined by reverse transcription-quantitative polymerase
      chain reaction. The results revealed that H2O2 induced notable injury to L02
      cells, as demonstrated by decreased cell viability, increased lactate
      dehydrogenase release, apoptotic rate and intracellular ROS production, and by
      the loss of MMP. Conversely, diosmetin (20-40 uM) significantly reversed the
      damaging effects of H2O2, which indicated that diosmetin may exhibit potent
      hepatoprotective potential against H2O2-induced oxidative damage. Furthermore,
      pretreatment with diosmetin elevated mRNA and protein expression levels of Nrf2,
      HO-1 and NQO1. The present study is the first, to the best of our knowledge, to
      demonstrate that activation of the Nrf2/NQO1-HO-1 signaling pathway maybe
      involved in the cytoprotective effects of diosmetin against oxidative stress.
      Therefore, diosmetin may be considered a promising therapeutic agent for the
      treatment of various liver diseases associated with oxidative stress.

PMID- 29568962
TI  - Dickkopf-3 upregulation mediates the cardioprotective effects of curcumin on
      chronic heart failure.
AB  - Curcumin, isolated from rhizome of turmeric, has been widely studied as a
      potential therapeutic drug for cancer. However, protective effects of curcumin on
      chronic heart failure (CHF) have not been fully studied. In the present study,
      the effects of curcumin on CHF and the underlying mechanisms were investigated. A
      total of 40 rabbits were randomized into 4 groups: Control rabbits fed with
      placebo (Con) or curcumin (Con-cur), CHF rabbits fed with placebo (CHF) or
      curcumin (CHF-cur). CHF was induced by volume and pressure overload. The effects
      of curcumin on cardiac function and left ventricular (LV) structure were assessed
      by echocardiography and histology. The effects of curcumin on CHF molecular
      biomarkers were detected by dihydroethidium and immunohistochemical staining. The
      effects of curcumin on Dickkopf-related protein 3 (DKK-3), p38 mitogen-activated
      protein kinase (p38), c-Jun N-terminal kinase (JNK) and apoptosis signal
      regulating kinase 1 (ASK1) were assessed by immunohistochemical staining and
      western blot analysis. Cardiac dysfunction and LV remodeling were successfully
      produced by ten weeks volume overload and eight weeks pressure overload in the
      CHF group. Compared with the Con group, the CHF group demonstrated higher levels
      of CHF molecular biomarkers, a lower level of DKK-3 expression and alterations of
      p38, JNK and ASK1 protein expression. Curcumin alleviated all those abnormalities
      markedly in the CHF-cur group. In summary, curcumin may exert cardioprotective
      effects by up-regulating DKK-3, which in turn may inhibit p38 and JNK signaling
      pathways in an ASK1-dependent way. The present study demonstrated that Dickkopf-3
      upregulation mediates the cardioprotective effects of curcumin on chronic heart
      failure for the first time.

PMID- 29568963
TI  - Microarray analysis of the expression profile of lncRNAs reveals the key role of
      lncRNA BC088327 as an agonist to heregulin-1beta-induced cell proliferation in
      peripheral nerve injury.
AB  - Heregulin-1beta is capable of promoting the nerve regeneration of acellular nerve
      allografts with skin-derived precursor differentiated Schwann cell (SC) therapy
      in peripheral nerve injury. Long non-coding RNAs (lncRNAs) serve important roles
      in the regulation of gene transcription and trans-lation in multiple biological
      processes, but its association with the repair of peripheral nerve injury is
      unexplored. Therefore, in the present study, the aim was to identify novel
      indicators for peripheral nerve injury, and to detect whether there is an
      association between lncRNA expression and the treatment effect of heregulin-1beta
      on this disorder. The expression status of lncRNAs and mRNAs in a well-built rat
      model with sciatic nerve injury was investigated using microarray assays. Based
      on the results of the microarray assays and quantitative polymerase chain
      reaction validation, it was inferred that lncRNA BC088327 was upregulated to the
      largest extent among all the lncRNAs. According to these findings, the role of
      BC088327 in peripheral nerve injury was further assessed by detecting the cell
      viability, cell cycle and apoptosis in a hypoxic SC cell model after suppressing
      the expression of BC088327 using specific small interfering RNA. Based on the
      results of the lncRNA microarray assay, 805 lncRNAs were significantly
      differentially expressed, among which, 323 lncRNAs were upregulated and 482
      lncRNAs were downregulated. Based on the results of the mRNA microarray assay,
      1,293 lncRNAs were significantly differentially expressed, including 603
      upregulated and 690 downregulated lncRNAs. Moreover, knockdown of lncRNA BC088327
      suppressed cell viability and induced cell apoptosis and S-phase cell cycle
      arrest in the SCs. In conclusion, expression profile changes of lncRNAs in
      peripheral nerve injuries were closely associated with treatment with heregulin
      1beta. lncRNA BC088327 may play a synergistic role with heregulin-1beta in
      repairing peripheral injury, which has the potential be a biomarker for the
      detection of peripheral injury and a medical target for the development of
      therapeutic modalities.

PMID- 29568965
TI  - Downregulation of lncRNA H19 inhibits the migration and invasion of melanoma
      cells by inactivating the NF-kappaB and PI3K/Akt signaling pathways.
AB  - As the most aggressive type of skin cancer, melanoma seriously affects human
      health. Long noncoding (lncRNA) 19 has been demonstrated to be involved in the
      progression of a number of different types of human cancers. However, the
      involvement of lncRNA H19 in melanoma remains unknown. Therefore, the present
      study was performed to investigate the roles of H19 in the development and
      progression of melanoma. In the present study, 49 patients with melanoma were
      included. Expression of lncRNA H19 in tumor tissue, adjacent healthy tissue and
      various cell lines with different treatments was measured by reverse
      transcription-quantitative polymerase chain reaction. The effects of H19
      knockdown on melanoma cell proliferation, migration and invasion were detected by
      cell counting kit-8, wound-healing and transwell invasion assays, respectively.
      In addition, the effects of H19 knockdown on the expression of nuclear factor
      (NF)-kappaB pathway-associated proteins were investigated by western blotting.
      The results revealed that the expression level of H19 was significantly higher in
      tumor tissue than in the adjacent healthy tissue of 47 out of 49 patients. H19
      knockdown significantly reduced the proliferation, migration and invasion ability
      of melanoma cells. H19 knockdown also inactivated the phosphoinositide 3-kinase
      (PI3K)/protein kinase B (Akt) pathway, which in turn inhibited the activation of
      the NF-kappaB signaling pathway. Thus, downregulation of lncRNA H19 may inhibit
      the migration and invasion of melanoma cells by inactivating the NF-kappaB
      signaling pathway via the inactivation of the PI3K/Akt signaling pathway. The
      present study provided references for future studies on the pathogenesis of
      melanoma and the clinical treatment of this disease.

PMID- 29568966
TI  - PPP2R2D, a regulatory subunit of protein phosphatase 2A, promotes gastric cancer
      growth and metastasis via mechanistic target of rapamycin activation.
AB  - Protein phosphatase 2A (PP2A) is an essential serine/threonine protein
      phosphatase that regulates the basic activities of eukaryotes by
      dephosphorylating its substrates. The function and substrate specificity of PP2A
      are generally determined by its regulatory subunits. In the present study, the
      clinical significance and roles of PPP2R2D, one of the regulatory subunits of
      PP2A, were demonstrated in gastric cancer (GC) carcinogenesis. Through a tissue
      microarray and quantitative polymerase chain reaction analysis, it was
      demonstrated that PPP2R2D was commonly upregulated in GC samples. This
      upregulation was positively correlated with the patients' tumor stage (P<0.01), T
      classification (P<0.01) and N classification (P=0.01). Furthermore, a high
      expression of PPP2R2D was closely associated with poor prognosis of patients.
      Knockdown of PPP2R2D significantly inhibited the proliferation and migration of
      GC cells in vitro, as well as the tumorigenicity and metastasis in vivo in an
      animal GC model. By contrast, overexpression of PPP2R2D promoted GC cell
      proliferation and migration in vitro. The analysis of underlying mechanisms
      indicated that PPP2R2D silencing decreased the phosphorylation level of
      mechanistic target of rapamycin (mTOR), thereby implicating that PPP2R2D is
      involved in the regulation of mTOR activity during tumorigenesis. Thus, the
      findings of the present study suggested that PPP2R2D may serve as a potential
      oncogene in GC and as a novel target for therapeutic strategies against this
      disease.

PMID- 29568964
TI  - Disruption of IGF-1R signaling by a novel quinazoline derivative, HMJ-30,
      inhibits invasiveness and reverses epithelial-mesenchymal transition in
      osteosarcoma U-2 OS cells.
AB  - Osteosarcoma is the most common primary malignancy of the bone and is
      characterized by local invasion and distant metastasis. Over the past 20 years,
      long-term outcomes have reached a plateau even with aggressive therapy.
      Overexpression of insulin-like growth factor 1 receptor (IGF-1R) is associated
      with tumor proliferation, invasion and migration in osteosarcoma. In the present
      study, our group developed a novel quinazoline derivative, 6-fluoro-2-(3
      fluorophenyl)-4-(cyanoanilino)quinazoline (HMJ-30), in order to disrupt IGF-1R
      signaling and tumor invasiveness in osteosarcoma U-2 OS cells. Molecular
      modeling, immune-precipitation, western blotting and phosphorylated protein
      kinase sandwich ELISA assays were used to confirm this hypothesis. The results
      demonstrated that HMJ-30 selectively targeted the ATP-binding site of IGF-1R and
      inhibited its downstream phosphoinositide 3-kinase/protein kinase B, Ras/mitogen
      activated protein kinase, and IkappaK/nuclear factor-kappaB signaling pathways in
      U-2 OS cells. HMJ-30 inhibited U-2 OS cell invasion and migration and
      downregulated protein levels and activities of matrix metalloproteinase (MMP)-2
      and MMP-9. An increase in protein levels of tissue inhibitor of metalloproteinase
      (TIMP)-1 and TIMP-2 was also observed. Furthermore, HMJ-30 caused U-2 OS cells to
      aggregate and form tight clusters, and these cells were flattened, less elongated
      and displayed cobblestone-like shapes. There was an increase in epithelial
      markers and a decrease in mesenchymal markers, indicating that the cells
      underwent the reverse epithelial-mesenchymal transition (EMT) process. Overall,
      these results demonstrated the potential molecular mechanisms underlying the
      effects of HMJ-30 on invasiveness and EMT in U-2 OS cells, suggesting that this
      compound deserves further investigation as a potential anti-osteosarcoma drug.

PMID- 29568967
TI  - Novel MSH2 splice-site mutation in a young patient with Lynch syndrome.
AB  - Lynch Syndrome (LS) is associated with germline mutations in one of the mismatch
      repair (MMR) genes, including MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6,
      PMS1 homolog 2, mismatch repair system component (PMS2), MLH3 and MSH3. The
      mutations identified in MMR genes are point mutations or large rearrangements.
      The point mutations are certainly pathogenetic whether they determine formation
      of truncated protein. The mutations that arise in splice sites are classified as
      'likely pathogenic' variants. In the present study, a novel splicing mutation was
      identified, (named c.212-1g>a), in the MSH2 gene. This novel mutation in the
      consensus splice site of MSH2 exon 2 leads to the loss of the canonical splice
      site, without skipping in-frame of exon 2; also with the formation of 2 aberrant
      transcripts, due to the activation of novel splice sites in exon 2. This mutation
      was identified in a young patient who developed colon cancer at the age of 26
      years and their belongs to family that met the 'Revised Amsterdam Criteria'. The
      present study provided insight into the molecular mechanism determining the
      pathogenicity of this novel MSH2 mutation and it reaffirms the importance of
      genetic testing in LS.

PMID- 29568968
TI  - Screening of potential biomarkers in uterine leiomyomas disease via gene
      expression profiling analysis.
AB  - The present study aimed to screen potential biomarkers for uterine leiomyomas
      disease, particularly target genes associated with the mediator of RNA polymerase
      II transcription subunit 12 (MED12) mutation. The microarray data of GSE30673,
      including 10 MED12 wild-type myometrium, 8 MED12 mutation leiomyoma and 2 MED12
      wild-type leiomyoma samples, were downloaded from the Gene Expression Omnibus
      database. Compared with myometrium samples, differently-expressed genes (DEGs) in
      the MED12 mutation and wild-type leiomyoma samples were identified using the
      Limma package. The two sets of DEGs obtained were intersected to screen common
      DEGs. The DEGs in the MED12 mutation and wild-type leiomyoma samples, and common
      DEGs were defined as group A, B and C. Gene Ontology (GO) and pathway enrichment
      analyses were performed using the Database for Annotation, Visualization and
      Integrated Discovery online tool. Based on the Kyoto Encyclopedia of Genes and
      Genomes database, pathway relation networks were constructed. DEGs in GO terms
      and pathways were intersected to screen important DEGs. Subsequently, a gene co
      expression network was constructed and visualized using Cytoscape software.
      Reverse transcription-quantitative polymerase chain reaction was used to detect
      the expression levels of important DEGs. A total of 1,258 DEGs in group A were
      screened, and enriched for extracellular matrix (ECM) organization and ECM
      receptor interaction. In addition, a total of 1,571 DEGs in group B were enriched
      for cell adhesion. Furthermore, 391 DEGs were involved in extracellular matrix
      organization. Pathway relation networks of group A, B and C were constructed with
      nodes of 48, 39, and 28, respectively. Finally, 135 important DEGs were obtained,
      including Acyl-CoA synthetase medium-chain family member 3, protein S (alpha)
      (PROS1) and F11 receptor. A gene co-expression network with 68 nodes was
      constructed. The expression of caspase 1 (CASP1) and aldehyde dehydrogenase 1
      family member A1 (ALDH1A1) was significant higher in SK-UT-1 compared with that
      in PHM1-31 cells, while the expression of PROS1 was significant lower in SK-UT-1
      cells. These results that CASP1, ALDH1A1 and PROS1 may be potential biomarkers
      for uterine leiomyomas. Furthermore, hematopoietic prostaglandin D synthase and
      carbonyl reductase 3 (CBR3) may be particular genes associated with the MED12
      mutation in this disease.

PMID- 29568969
TI  - miR-133b-5p contributes to hypoxic preconditioning-mediated cardioprotection by
      inhibiting the activation of caspase-8 and caspase-3 in cardiomyocytes.
AB  - In a previous study using a microRNA (miRNA/miR) microarray assay, we
      demonstrated that miR-133b-5p was upregulated in response to hypoxic
      preconditioning (HPC). The present study was designed to investigate the role of
      the miR-133b-5p in HPC-induced cardioprotection and the underlying mechanisms
      involving caspase-8 and caspase-3 apoptotic signaling. Adult rats were subjected
      to myocardial ischemia/reperfusion (I/R) injury with or without ischemic
      preconditioning (IPC), and the level of miR-133b-5p in myocardium was measured.
      Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation
      (H/R) injury, with or without HPC. miR-133b-5p antagomir was transfected into the
      cardiomyocytes to observe whether it could block HPC-induced cardioprotection.
      Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase
      (LDH) activity and apoptotic rate. Reverse transcription-quantitative polymerase
      chain reaction was used to measure the level of miR-133b-5p. The activation of
      caspase-8 and caspase-3 were measured by western blot analysis to detect the
      cleaved fragments as well as a colorimetric assay. Following myocardial I/R
      injury, the expression of miR-133b-5p was decreased in myocardium, while this
      decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against
      H/R injury by increasing cell viability, while reducing LDH release and cell
      apoptosis. These protective effects were coupled with the upregulation of miR
      133b-5p. However, the knockdown of miR-133b-5p in the cardiomyocytes blocked HPC
      mediated cardioprotection as reflected by the aggravation of cell injury and
      apoptosis. HPC upregulated miR-133b-5p level was markedly suppressed by the
      antagomir. In addition, the cleavage and activities of caspase-8 and caspase-3
      were inhibited by HPC while reversed by knockdown of miR-133b-5p. Upregulation of
      miR-133b-5p contributes to HPC-mediated cardioprotection in cardiomyocytes, and
      the mechanism may be associated with inhibition of caspase-8 and caspase-3
      apoptotic signaling.

PMID- 29568971
TI  - Abstracts from the 9th International Symposium of Clinical and Applied Anatomy
      (ISCAA), September 9-12, 2017 Innsbruck, Austria.

PMID- 29568970
TI  - miR-494-BAG-1 axis is involved in cinobufacini-induced cell proliferation and
      apoptosis in gastric cancer.
AB  - Cinobufacini is widely used in the treatment of advanced cancers. It has been
      previously reported that microRNA (miR)-494 was upregulated in cinobufacini
      treated gastric cancer cells; however, the detailed role of miR-494 in the anti
      tumor activity of cinobufacini is unclear. The present study aimed to clarify the
      function of miR-494 in cinobufacini-induced cell behavior changes. Cell viability
      and proliferation ability were investigated using a Cell Counting Kit-8 assay.
      Flow cytometry was performed to investigate the apoptosis rate of gastric cancer
      (GC) cells. The mRNA expression levels of microRNA (miR)-494 and BCL2 associated
      athanogene 1 (BAG-1) were investigated using reverse transcription-quantitative
      polymerase chain reaction, and the protein expression level of BAG-1 was
      investigated using western blot assays. The results demonstrated that treatment
      with cinobufacini suppressed proliferation and promoted apoptosis of gastric
      cancer cells. miR-494 acts as a tumor suppressor gene in gastric cancer. In
      cinobufacini-treated cells, miR-494 and BAG-1 exhibited opposing expression
      trends. Furthermore, knockdown of miR-494 in cinobufacini-treated cells
      upregulated the protein expression level of BAG-1, promoted cell proliferation
      and inhibited cell apoptosis. In addition, inhibition of BAG-1 using small
      interfering RNA in cinobufacini-treated cells partially abrogated the effects of
      miR-494 inhibitor on cell proliferation and apoptosis. Thus, these results
      suggest that cinobufacini suppresses GC cells proliferation and promotes
      apoptosis partially through the regulation of miR-494-BAG-1 axis, which may
      provide a novel insight into the functional mechanism of cinobufacini.

PMID- 29568972
TI  - Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.
AB  - Abnormal activation of the innate immune system is a common feature of autoimmune
      and chronic inflammatory diseases. Since their identification as a separate
      family of leukocytes, innate lymphoid cells (ILCs) have emerged as important
      effector cells of the innate immune system. Alterations in ILC function and
      subtype distribution have been observed in a variety of immune-mediated diseases
      in humans and evidence from experimental models suggests a subtype specific role
      of ILCs in the pathophysiology of autoimmune inflammation. In this review, we
      discuss recent advances in the understanding of ILC biology in autoimmune and
      chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel
      diseases, psoriasis, and rheumatic diseases, with a special focus on the
      potential of ILCs as therapeutic targets for the development of novel treatment
      strategies in humans.

PMID- 29568974
TI  - The Cartilage Warp Prevention Suture.
AB  - BACKGROUND: Costal cartilage graft warping can challenge rhinoplasty surgeons and
      compromise outcomes. We propose a technique, the "warp control suture," for
      eliminating cartilage warp and examine outcomes in a pilot group. METHODS: The
      warp control suture is performed in the following manner: Harvested cartilage is
      cut to the desired shape and immersed in saline to induce warping. A 4-0 or 5-0
      PDS suture, depending the thickness of the cartilage, is passed from convex to
      concave then concave to convex side several times about 5-6 mm apart, finally
      tying the suture on the convex side with sufficient tension to straighten the
      cartilage. First an ex vivo experiment was performed in 10 specimens from 10
      different patients. Excess cartilage was sutured and returned to saline for a
      minimum of 15 min and then assessed for warping compared to cartilage cut in the
      identical shape also soaked in saline. Then, charts of nine subsequent patients
      who received the warp control suture on 16 cartilage grafts by the senior author
      (BG) were retrospectively reviewed. Inclusion of study subjects required at least
      6 months of follow-up with standard rhinoplasty photographs. Postoperative
      complications and evidence of warping were recorded. RESULTS: In the ex vivo
      experiment, none of the 10 segments demonstrated warping after replacement in
      saline, whereas all the matching segments demonstrated significant additional
      warping. Clinically, no postoperative warping was observed in any of the nine
      patients at least 6 months postoperatively. One case of minor infection was
      observed in an area away from the graft and treated with antibiotics. No warping
      or other complications were noted. CONCLUSION: The warp control suture technique
      presented here effectively straightens warped cartilage graft and prevents
      additional warping. 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- 29568975
TI  - Safety of brotizolam in hospitalized patients.
AB  - PURPOSE: The objective of this study was to evaluate the safety of brotizolam in
      hospitalized patients. METHODS: A single-center, comparative retrospective cohort
      analysis of patients hospitalized in internal medicine wards. Patients treated
      with brotizolam were compared to patients not treated with any benzodiazepines
      during hospitalization. Primary outcome was any of the following safety events:
      mechanical ventilation, delirium, and falls. RESULTS: Six hundred patients were
      included after exclusion in the final analysis; 300 treated with brotizolam
      (treatment) and 300 not treated with any benzodiazepines (comparator). The
      brotizolam-treated patients were older with more comorbidities and psychotropic
      medications. After adjustment using multivariate logistic regression analysis
      with propensity score, the primary outcomes occurred at significantly higher
      rates in treated patients than in untreated patients (17 vs. 2 events; OR =
      7.33). Any psychotropic medication administered during hospitalization was found
      by logistic regression to be the main independent risk factor for the studied
      safety outcomes while age, comorbidities, and the cause of hospitalization were
      not. CONCLUSIONS: Treatment with brotizolam during hospitalization in internal
      medicine wards is linked to a higher risk of respiratory deterioration, delirium,
      and falls. Use of psychotropic medications during hospitalization is the main
      independent risk factor of safety outcomes. Further research is needed to fully
      evaluate the risks and benefits of sleep induction medications in hospitals.

PMID- 29568973
TI  - Neurogenic inflammation and its role in migraine.
AB  - The etiology of migraine pain involves sensitized meningeal afferents that
      densely innervate the dural vasculature. These afferents, with their cell bodies
      located in the trigeminal ganglion, project to the nucleus caudalis, which in
      turn transmits signals to higher brain centers. Factors such as chronic stress,
      diet, hormonal fluctuations, or events like cortical spreading depression can
      generate a state of "sterile inflammation" in the intracranial meninges resulting
      in the sensitization and activation of trigeminal meningeal nociceptors. This
      sterile inflammatory phenotype also referred to as neurogenic inflammation is
      characterized by the release of neuropeptides (such as substance P, calcitonin
      gene related peptide) from the trigeminal innervation. This release leads to
      vasodilation, plasma extravasation secondary to capillary leakage, edema, and
      mast cell degranulation. Although neurogenic inflammation has been observed and
      extensively studied in peripheral tissues, its role has been primarily
      investigated in the genesis and maintenance of migraine pain. While some aspects
      of neurogenic inflammation has been disregarded in the occurrence of migraine
      pain, targeted analysis of factors have opened up the possibilities of a dialogue
      between the neurons and immune cells in driving such a sterile neuroinflammatory
      state in migraine pathophysiology.

PMID- 29568976
TI  - Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an
      explorative study in healthy volunteers.
AB  - PURPOSE: This study aimed to develop a model for pharmacodynamic and
      pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism
      and to compare a high-concentration/low-volume intranasal naloxone formulation 8
      mg/ml to intramuscular 0.8 mg. METHODS: Two-way crossover in 12 healthy
      volunteers receiving naloxone while receiving remifentanil by a target-controlled
      infusion for 102 min. The group were subdivided into three different doses of
      remifentanil. Blood samples for serum naloxone concentrations, pupillometry and
      heat pain threshold were measured. RESULTS: The relative bioavailability of
      intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in
      antagonism; the effect was significant in the data set as a whole (p < 0.001) and
      in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no
      statistical difference. CONCLUSIONS: A target-controlled infusion of remifentanil
      provides good conditions for studying the pharmacodynamics of naloxone, and
      pupillometry was a better modality than heat pain threshold. Intranasal naloxone
      0.8 mg is inferior for a similar dose intramuscular. Our design may help to
      bridge the gap between studies in healthy volunteers and the patient population
      in need of naloxone for opioid overdose. TRIAL REGISTRATION: clinicaltrials.gov :
      NCT02307721.

PMID- 29568977
TI  - In silico analysis of endogenous siRNAs associated transposable elements and NATs
      in Schistosoma japonicum reveals their putative roles during reproductive
      development.
AB  - Schistosomiasis is a neglected tropical disease caused by trematode of the genus
      Schistosoma. Successful reproductive development is critical for the production
      of eggs, which are responsible for host pathology and disease dissemination.
      Endogenous small non-coding RNAs play important roles in many biological
      processes such as protection against foreign pathogens, cell differentiation, and
      chromosomal stability by regulating target gene expression at the transcriptional
      and post-transcriptional levels. In this study, we performed in silico analysis
      of endogenous small non-coding RNAs in different stages, and sex of S. japonicum
      focusing on endogenous small interfering RNAs (endo-siRNAs) generated from
      transposable elements (TEs) and natural antisense transcripts (NATs). Both total
      and unique siRNA populations show 18-30 nt in length, but the predominant size
      was 20 nt and the leading first base was adenosine. Sense TE-derived endo-siRNAs
      reads were higher than antisense reads at different relative positions of TEs,
      whereas no such difference was observed for NAT-derived endo-siRNAs. TE- and NAT
      derived endo-siRNAs were more enriched in the male compared to female worms, with
      the higher relative expression in early phase of pairing. Putative targets of
      endo-siRNAs indicated more of them in males (106 and 66) than in females (6 and
      23) for TE- and NAT-derived endo-siRNAs, respectively. Our preliminary study
      revealed vital role of endo-siRNAs during the reproductive development of S.
      japonicum and provide clues for putative novel targets to suppress worm
      reproduction and direction for effective anti-schistosomal drug development.

PMID- 29568978
TI  - Apoptotic impact on Brugia malayi by sulphonamido-quinoxaline: search for a novel
      therapeutic rationale.
AB  - Human lymphatic filariasis although not fatal but poses serious socioeconomic
      burden due to associated disability. This is reflected by the huge magnitude of
      the estimated disability-adjusted life years of about 5.09 million. Therefore,
      following WHO mandate, our earlier studies on antifilarial drug development
      revealed the significance of apoptosis. Apoptotic impact has been implicated in
      anticancer rationale of several drugs. In this study, we explored the
      antifilarial potential of sulphonamido-quinoxaline compounds, shown to be
      specific inhibitor for c-Met kinase in human cancer cells. Out of studied
      compounds, Q4, showing favorable drug-likeness and medicinal chemistry properties
      on bioinformatics platform along with subsequently recorded lowest IC100 value,
      was considered as a suitable antifilarial candidate. Significant apoptosis due to
      mitochondrial involvement was recorded in drug-treated parasite unlike untreated
      control. In spite of homology between human c-Met kinase and Brugia malayi
      counterpart, comparative docking result of this compound showed more favorable
      binding parameters with the parasitic target. The wide gap between IC100 and LD50
      values further confirmed the therapeutic safety. We propose sulphonamido
      quinoxaline derivative as a lead candidate for antifilarial drug development.
      Further study is warranted to authenticate parasitic c-Met kinase as a novel
      therapeutic target reminiscent of anticancer rationale implicating inhibition of
      proliferation.

PMID- 29568979
TI  - Comparison of catheter-over-needle and catheter-through-needle on leakage from
      the catheter insertion site during continuous femoral nerve block.
AB  - The aim of this study was to compare the incidences of leakage from the catheter
      insertion site during continuous femoral nerve block when using the catheter
      through-needle, Contiplex TouhyTM (CT) and the newly developed catheter-over
      needle, Contiplex CTM (CC). Forty adult patients who were scheduled to undergo
      continuous femoral nerve block for pain control following knee surgery were
      enrolled and were randomly assigned to a CT group or a CC group. After finishing
      surgery, a catheter for continuous femoral nerve block was placed using
      ultrasound. A catheter was advanced along the femoral nerve 5-6 cm beyond the
      needle tip. Then 0.25% levobupivacaine was continuously administered at a rate of
      5 ml/h until 9:00 am on postoperative day 1. The incidence of leakage of the
      local anesthetic from the insertion site in the CT group was significantly higher
      than that in the CC group. In the CT group, leakage from the catheter insertion
      site was observed in 11 of 20 patients during the observation period. On the
      other hand, none of the patients in the CC group showed leakage. Contiplex CTM is
      more effective than Contiplex TouphyTM for prevention of leakage of local
      anesthetics from the insertion site during continuous femoral nerve block.

PMID- 29568980
TI  - Sleep Apnea in Heart Failure.
AB  - PURPOSE OF REVIEW: In this review, we discuss the current treatment options for
      sleep-disordered breathing (SDB) in patients with heart failure (HF). We address
      the role of positive airway pressure (PAP) devices and other emerging therapies.
      The review includes discussion of recent trials that reported negative
      consequences for the PAP devices in patients with heart failure. RECENT FINDINGS:
      Optimal guideline-directed medical therapies of HF and PAP devices have been the
      mainstay treatments for HF patients with SDB. Recently, randomized controlled
      trials (RCTs) evaluated the effect of PAP on clinical outcomes in patients with
      cardiovascular (CV) disease and heart failure and found no benefit in decreasing
      fatal and non-fatal CV events. The Sleep Apnea Cardiovascular Endpoints (SAVE)
      trial evaluated continuous positive airway pressure (CPAP) ventilation in
      patients with CV disease and obstructive sleep apnea (OSA) and did not observe
      any improvement in CV effect. In patients with HF and central sleep apnea (CSA),
      adaptive servo-ventilation (ASV) was hypothesized to help HF outcomes, but the
      Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure
      (SERVE-HF) trial did not show any mortality benefit. Instead, the trial suggested
      an increase in all-cause and CV mortality in the treatment arm. currently,
      studies have not shown the use of PAP therapy to improve any risks of CV outcomes
      or death in HF patients with sleep apnea, but some associations with improvements
      in symptoms from OSA have been observed.

PMID- 29568983
TI  - Model Prediction and Validation of an Order Mechanism Controlling the
      Spatiotemporal Phenotype of Early Hepatocellular Carcinoma.
AB  - Recently, hepatocyte-sinusoid alignment (HSA) has been identified as a mechanism
      that supports the coordination of hepatocytes during liver regeneration to
      reestablish a functional micro-architecture (Hoehme et al. in Proc Natl Acad Sci
      107(23):10371-10376, 2010). HSA means that hepatocytes preferentially align along
      the closest micro-vessels. Here, we studied whether this mechanism is still
      active in early hepatocellular tumors. The same agent-based spatiotemporal model
      that previously correctly predicted HSA in liver regeneration was further
      developed to simulate scenarios in early tumor development, when individual
      initiated hepatocytes gain increased proliferation capacity. The model
      simulations were performed under conditions of realistic liver micro
      architectures obtained from 3D reconstructions of confocal laser scanning
      micrographs. Interestingly, the established model predicted that initiated
      hepatocytes at first arrange in elongated patterns. Only when the tumor
      progresses to cell numbers of approximately 4000, does it adopt spherical
      structures. This prediction may have relevant consequences, since elongated
      tumors may reach critical structures faster, such as larger vessels, compared to
      a spherical tumor of similar cell number. Interestingly, this model prediction
      was confirmed by analysis of the spatial organization of initiated hepatocytes in
      a rat liver tumor initiation study using single doses of 250 mg/kg of the
      genotoxic carcinogen N-nitrosomorpholine (NNM). Indeed, small clusters of GST-P
      positive cells induced by NNM were elongated, almost columnar, while larger GDT-P
      positive foci of approximately the size of liver lobuli adopted spherical shapes.
      From simulations testing numerous possible mechanisms, only HSA could explain the
      experimentally observed initial deviation from spherical shape. The present study
      demonstrates that the architecture of small cell clusters of hepatocytes early
      after initiation is still controlled by physiological mechanisms. However, this
      coordinating influence is lost when the tumor grows to approximately 4000 cells,
      leading to further growth in spherical shape. Our findings stress the potential
      importance of organ micro-architecture in understanding tumor phenotypes.

PMID- 29568982
TI  - Intrafollicular thyroid hormone staining in whole-mount zebrafish (Danio rerio)
      embryos for the detection of thyroid hormone synthesis disruption.
AB  - Endocrine-disrupting chemicals are known to impact multiple hormonal axes of
      vertebrates, among which the thyroid system is crucial for multiple developmental
      and physiological processes. Thus, the present study focused on the semi
      quantitative visualization of intrafollicular triiodothyronine (T3) and thyroxin
      (T4) in zebrafish embryos as a potential test system for the detection of
      disrupted thyroid hormone synthesis. To this end, an antibody-based fluorescence
      double-staining protocol for whole-mount zebrafish embryos and larvae was adapted
      to simultaneously detect intrafollicular T3 and T4. During normal development
      until 10 days post-fertilization (dpf), the number of thyroid follicles increased
      along the ventral aorta. Concentrations of T4 and T3, measured by fluorescence
      intensity, increased until 6 dpf, but decreased thereafter. Exposure of zebrafish
      embryos to propylthiouracil (PTU), a known inhibitor of TH synthesis, resulted in
      a significant decrease in the number of follicles that stained for T3, whereas a
      trend for increase in follicles that stained for T4 was observed. In contrast,
      fluorescence intensity for both thyroid hormones decreased significantly after
      exposure to PTU. Overall, the zebrafish embryo appears to be suitable for the
      simultaneous visualization and detection of changing intrafollicular TH contents
      during normal development and after PTU treatment.

PMID- 29568984
TI  - Malnutrition After Bariatric Surgery Requiring Artificial Nutrition Supplies.

PMID- 29568981
TI  - Three-dimensional organization and dynamics of the genome.
AB  - Genome is a complex hierarchical structure, and its spatial organization plays an
      important role in its function. Chromatin loops and topological domains form the
      basic structural units of this multiscale organization and are essential to
      orchestrate complex regulatory networks and transcription mechanisms. They also
      form higher-order structures such as chromosomal compartments and chromosome
      territories. Each level of this intrinsic architecture is governed by principles
      and mechanisms that we only start to understand. In this review, we summarize the
      current view of the genome architecture on the scales ranging from chromatin
      loops to the whole genome. We describe cell-to-cell variability, links between
      genome reorganization and various genomic processes, such as chromosome X
      inactivation and cell differentiation, and the interplay between different
      experimental techniques.

PMID- 29568987
TI  - Furosemide-induced tubular dysfunction responding to prostaglandin synthesis
      inhibitor therapy in a child with nephrotic syndrome.
AB  - Furosemide is one of the most common drug used to treat anasarca in childhood
      nephrotic syndrome. It has minimal side effects on short-term usage, but
      prolonged use can result in polyuria, hypokalemia and metabolic alkalosis. This
      pseudo-bartter complication can be treated by discontinuation of the drug with
      adequate potassium replacement. We report a child who was given furosemide for 20
      days elsewhere to treat the edema due to nephrotic syndrome and then presented to
      us with bartter-like syndrome. Furosemide was discontinued and potassium
      replacement was initiated. However, the child continued to have polyuria leading
      to repeated episodes of hypotensive shock. In view of severe symptoms, she was
      given a short course of oral indomethacin for 6 days, to which she responded.
      This case highlights the fact that indomethacin can provide symptomatic
      improvement in furosemide induced pseudo-bartter.

PMID- 29568986
TI  - Can a workplace leadership intervention reduce job insecurity and improve health?
      Results from a field study.
AB  - PURPOSE: To examine the effectiveness of an intervention in the workplace
      designed to reduce job insecurity among employees affected by organizational
      change. METHODS: Supervisors were randomly allocated to an intervention (IG) or
      waiting-list-control group (CG) and the intervention was administered over a
      period of 3 months, comprising six group sessions. N = 103 supervisors and their
      team members (mean age 41.80 +/- 9.60 years, 60.19% male) provided data prior to
      (t0) and 3 months post-intervention (t1) by means of questionnaires and hair
      samples. Job insecurity (COPSOQ), mental health (HADS) and somatic health (GBB,
      hair cortisol concentration) were measured. RESULTS: Job insecurity was reduced
      to a marginally significant degree in the IG compared to the CG at t1 (B = -
      5.78, p = .06, CI [- 11.73, 0.17]). Differential effects for supervisors and team
      members were not found. No effects on health could be observed overall in the IG,
      but supervisors in the IG reported a significant decrease in exhaustion tendency
      (B = - 0.92, p = 0.01, CI [- 1.64, - 0.20]) and a non-significant trend towards
      higher levels of anxiety (B = 2.98, p = 0.10, CI [- 0.57, 6.54]) compared to team
      members. CONCLUSIONS: This is the first study to provide some evidence for the
      effectiveness of an intervention that aimed at reducing job insecurity during
      organizational change. Health-related effects were observed in supervisors but
      not in team members. Further intervention studies are needed to add to the
      current knowledge base.

PMID- 29568988
TI  - Late-onset hemophagocytic lymphohistiocytosis with varicella zoster virus and
      Epstein-Barr virus co-infection after umbilical cord blood transplantation.

PMID- 29568985
TI  - Organ-specific metastasis of breast cancer: molecular and cellular mechanisms
      underlying lung metastasis.
AB  - BACKGROUND: Breast cancer (BC) is the most common type of cancer in women and the
      second cause of cancer-related mortality world-wide. The majority of BC-related
      deaths is due to metastasis. Bone, lung, brain and liver are the primary target
      sites of BC metastasis. The clinical implications and mechanisms underlying bone
      metastasis have been reviewed before. Given the fact that BC lung metastasis
      (BCLM) usually produces symptoms only after the lungs have been vastly occupied
      with metastatic tumor masses, it is of paramount importance for diagnostic and
      prognostic, as well as therapeutic purposes to comprehend the molecular and
      cellular mechanisms underlying BCLM. Here, we review current insights into the
      organ-specificity of BC metastasis, including the role of cancer stem cells in
      triggering BC spread, the traveling of tumor cells in the blood stream and their
      migration across endothelial barriers, their adaptation to the lung
      microenvironment and the initiation of metastatic colonization within the lung.
      CONCLUSIONS: Detailed understanding of the mechanisms underlying BCLM will shed a
      new light on the identification of novel molecular targets to impede daunting
      pulmonary metastases in patients with breast cancer.

PMID- 29568990
TI  - Necrobiotic xanthogranuloma: a 30-year single-center experience.
AB  - To characterize the clinical features, associated disorders, and treatment of
      necrobiotic xanthogranuloma (NXG), a rare non-Langerhans cell histiocytosis, we
      conducted a retrospective review of pathologically confirmed NXG at Mayo Clinic
      Arizona from 1987 to June 2017. Data on clinical findings, laboratory findings,
      associated disorders, therapy, and response to therapy were extracted. Nineteen
      patients were identified. Mean age was 54 years (range, 17-84) with equal gender
      distribution. Median follow-up was 5.5 years (range, 1-18). Most patients had a
      detectable monoclonal protein (84%), and IgG kappa constituted 58%. The most
      common cutaneous lesions involved the periorbital region (53%). The majority of
      patients had extracutaneous manifestations, most commonly affecting the liver
      (32%) and the sinuses (21%). Hematologic malignancies were diagnosed in 26% of
      patients and included Hodgkin lymphoma, chronic lymphocytic leukemia (CLL),
      smoldering myeloma, and multiple myeloma. The most common treatment was
      chlorambucil with or without systemic corticosteroids. Response was seen in most
      patients (95%), and most patients received 1-3 lines of therapy (74%). NXG is a
      reactive histiocytic disorder that commonly involves multiple organ systems and
      requires a high degree of clinical suspicion for accurate diagnosis. Treatment
      decisions should be based on coexisting conditions and pattern of disease
      involvement.

PMID- 29568991
TI  - Large granular lymphocytic leukemia-associated peripheral neuropathy.

PMID- 29568989
TI  - Major response of PNH to an AML chemotherapy protocol.

PMID- 29568993
TI  - Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells
      from lung cancer patients following long-term cancer peptide vaccination.
AB  - Therapeutic cancer peptide vaccination is an immunotherapy designed to elicit
      cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic
      vaccination trials have been performed, nevertheless there are only a few reports
      that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen
      specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of
      vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral
      blood mononuclear cells (PBMCs) from two lung cancer patients over the course of
      long-term vaccine therapy. In both patients, vaccination with two epitope
      peptides derived from cancer/testis antigens (upregulated lung cancer 10 (URLC10)
      and cell division associated 1 (CDCA1)) induced specific CTLs expressing various
      TCRs. All URLC10-specific CTL clones tested showed Ca2+ influx, IFN-gamma
      production, and cytotoxicity when co-cultured with URLC10-pulsed tumor cells.
      Moreover, in CTL clones that were not stained with the URLC10/MHC-multimer, the
      CD3 zeta chain was not phosphorylated. NGS of the TCR repertoire of bulk PBMCs
      demonstrated that the frequency of vaccine peptide-specific CTL clones was near
      the minimum detectable threshold level. These results demonstrate that
      vaccination induces antigen-specific CTLs expressing various TCRs at different
      time points in cancer patients, and that some CTL clones are maintained in PBMCs
      during long-term treatment, including some with TCRs that do not bind peptide/MHC
      multimer.

PMID- 29568992
TI  - IgG synthesis rate and anti-myelin oligodendrocyte glycoprotein antibody in CSF
      may be associated with the onset of CNS demyelination after haplo-HSCT.
AB  - Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and
      effective therapy for hematology patients, but it usually has many complications,
      such as neurological complications. As one of the neurological complications
      following haplo-HSCT, immune-mediated demyelinating diseases of the central
      nervous system (CNS) seriously affect a patient's quality of life. However, the
      incidence, risk factors, and pathogenesis of CNS demyelination are not very well
      understood. Thirty of the 1526 patients (1.96%) suffered from CNS demyelination.
      In univariate analysis, we found that blood-brain barrier (BBB) permeability and
      the CSF IgG synthesis index (IgG-Syn) were related to the occurrence of CNS
      demyelination (p < 0.05). In a multivariate analysis, the IgG-Syn (OR = 1.017,
      95% CI 1.003-1.031, p = 0.019) and CSF anti-myelin oligodendrocyte glycoprotein
      antibody (MOG.Ab) (OR = 12.059, 95% CI 1.141-127.458, p = 0.038) were
      independently associated with the onset of CNS demyelination. We also studied the
      possible pathogenesis of CNS demyelination. Immune reconstitution (the cell
      proportions of CD19+ B cells, CD3+ T cells, and CD4+ T cells); the counts of
      leucocytes, lymphocytes, monocytes, and platelets; and the levels of
      immunoglobulins A, G, and M 30, 60, and 90 days after HSCT showed no significant
      differences between CNS demyelination and no demyelination (p > 0.05). The
      probabilities of overall survival showed no significant differences between
      patients with and without demyelination (p > 0.05). Only four deaths in 30
      patients, but bringing projected survival to less than 20%.We imply that IgG-Syn
      and CSF MOG. Ab may be associated with the onset of CNS demyelination during 2
      weeks of neurological symptoms in patients with brain or spinal cord MRI
      abnormality. Immune reconstitution may not be the pathogenesis of CNS
      demyelination.

PMID- 29568994
TI  - Preliminary evidence of nanoparticle occurrence in water from different regions
      of Delhi (India).
AB  - The objective of this study was to obtain preliminary evidence of metal-based
      nanoparticle (NP) occurrence in Delhi (India). Six sampling locations (inlets and
      outlets of two different municipal wastewater treatment plants (WWTPs),
      groundwater, and river water) were collected in three independent sampling
      events. Microscopic analysis (TEM) found majority (40%) of the particles ranged
      between 150 and 200 nm followed by particles of size 100-150 nm (22%) at the
      inlet of WWTP, while at outlet, 90% of the particles were < 100 nm. Compared with
      the outlet of the WWTPs, particles at the inlet were found to be greater than
      40%. Intensity-based particle size distribution (PSD) revealed particle size at
      influent in the range of 210 nm, while at effluent, particle size for both WWTPs
      ranged < 100 nm. Particles of size between 100 and 200 nm were found to get
      removed from both the treatment plants and thus making it evident that NP gets
      settled or adsorbed in sludge. Spectral analysis (EDX) further confirmed the
      presence of metals such as Al, As, Ag, Mn, Fe, Ti, and Zn at different weight
      percentages. Overall, findings of this study confirmed the presence of metal
      based engineered NPs (ENPs) from anthropogenic sources and it cannot also be
      ruled out the possible formation of NPs within the wastewater from natural
      minerals. Moreover, to solve definitive clues for ascertaining the sources of NPs
      in complex samples, more sophisticated research techniques, such as inductively
      coupled plasma-mass spectrometry (ICP-MS) in combination with field flow
      fractionation, single-particle ICP-MS, and radio-labeling in combination or in
      single should be considered.

PMID- 29568995
TI  - [Chronic prurigo].
AB  - Chronic prurigo is a disease characterized by the presence of chronic pruritus
      and singular or multiple usually hyperkeratotic symmetrically distributed itchy
      papules, nodules, and/or plaques. This condition is difficult to treat and leads
      to a substantial impairment of the quality of life. It may originate from
      dermatological, systemic, neurological, psychiatric/psychosomatic, multifactorial
      or unknown conditions causing itch, which lead to prolonged scratching behavior
      and sensitization mechanisms and ultimately to the development of pruriginous
      lesions. Thorough diagnostic efforts, including a detailed clinical history and
      physical examination, as well as targeted complementary examinations should be
      initiated as soon as possible. The German guideline recommends topical steroids
      and phototherapy as first-choice options. Pimecrolimus and capsaicin (topical),
      as well as antihistamines, anticonvulsants, and immunosuppressive drugs
      (systemic) should be considered as valid alternatives.

PMID- 29568996
TI  - [Side effects of biologic therapies in psoriasis].
AB  - BACKGROUND: The introduction of biologics has revolutionized the treatment of
      moderate to severe plaque psoriasis. Due to the continuous expansion of
      biological therapies for psoriasis, it is particularly important to acknowledge
      efficacy and safety of the compounds not only in clinical trials but also in long
      term registry-based observational studies. AIM: Typical side effects and
      significant risks of antipsoriatic biologic therapies considering psoriatic
      control groups are presented. MATERIALS AND METHODS: A selective literature
      search was conducted in PubMed and long-term safety studies of the psoriasis
      registries PsoBest, PSOLAR and BADBIR were evaluated. RESULTS AND DISCUSSION: To
      assess the long-term safety of biologics, the evaluation of the course of large
      patient cohorts in long-term registries is of particular medical importance.
      Newer biologic drugs seem to exhibit a better safety profile than older ones.

PMID- 29568997
TI  - [Severe skin reactions due to new medications].
AB  - Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and a specific
      form of hypersensitivity syndrome which is nowadays called "drug reaction with
      eosinophilia and systemic symptoms" (DRESS) are severe, mainly drug-induced skin
      reactions. Whereas SJS/TEN is considered one reaction entity of different
      severity, DRESS has to be distinguished from SJS/TEN but also from other severe
      exanthems due to multiorgan involvement. Although SJS/TEN is generally referred
      to as drug reaction, in total only about three quarters of the cases are actually
      caused by drugs. After the clinical diagnosis is made, identification of the
      potential inducing factor is most important. In case medications are considered
      as causal, their withdrawal plays a key role in management. In order to identify
      and withdraw the inducing agent, a detailed and thorough medication history must
      be obtained. Agents identified or confirmed as inducers of SJS/TEN by
      pharmacoepidemiological studies are allopurinol, antibacterial sulfonamides,
      various antiepileptics, nevirapine and nonsteroidal anti-inflammatory drugs of
      the oxicam-type. Among drugs inducing DRESS are also various antiepileptics, but
      in addition allopurinol, sulfonamides and minocycline. Some cases of SJS/TEN and
      DRESS associated with the use of new medication, including targeted therapies and
      biologicals, have been observed.

PMID- 29568998
TI  - [Cutaneous side effects of targeted therapies].

PMID- 29568999
TI  - HIV Risk and Gender in Jamaica's Homeless Population.
AB  - Rigorous HIV-related data for the homeless population in Jamaica is limited. A
      cross-sectional survey using a venue-based sampling approach was conducted in
      2015 to derive HIV prevalence and associated risk factors. Three hundred twenty
      three homeless persons from the parishes of St. James, St. Ann, Kingston, and St.
      Andrew (the main urban centers) participated. HIV prevalence was 13.8%, with a
      difference in gender (males 11.6%, females 26.7%, P = .007). Sex work, multiple
      partnerships, incarceration, non-injecting drug use, and female rape were common
      among the participants. Long-term, multilayered, HIV-specific, female-focused
      interventions are required for the population, along with additional female
      centric research.

PMID- 29569001
TI  - The alcohol-intoxicated trauma patient: impact on imaging and radiation exposure.
AB  - INTRODUCTION: The purpose of this study was to investigate the effects of alcohol
      intoxication in trauma patients in regard to its impact on application of
      computed tomography (CT) and associated radiation exposure. METHODS: We conducted
      a retrospective study from a continuous patient cohort. INCLUSION CRITERIA:
      admission to the emergency room of an urban Level 1 trauma center with trauma
      team activation during a 12-month period (Jan 1st-Dec 31st 2012). Patients with
      incomplete data, age <= 12 years and with neurological diseases were excluded.
      Demographics, mechanisms, severity and patterns of injury (Abbreviated Injury
      Scale, Injury Severity Score, Glasgow Coma Scale), blood alcohol concentration
      (BAC, in permille, 0/00), imaging studies (head/whole body CT), radiation
      exposure, and hospital length of stay, surgical procedures and mortality were
      evaluated with SPSS statistics (Version 25, IBM Inc., Armonk, New York). RESULTS:
      A positive BAC (mean 1.80 +/- 0.767) was reported in 19.2% (n = 41/214) of the
      cohort. Alcohol intoxication was associated with higher utilization of head CT
      (65.9 vs. 46.8%, p = 0.017) and radiation exposure (231.75 vs. 151.25 mAS, p =
      0.045; dose-length product, 583.03 vs. 391.04, p = 0.006). In general, the
      presence of alcohol was associated with over-triage (p = 0.001), despite minor
      injury severity (ISS < 9) and a comparable rate of head injuries (p = 0.275).
      Head injury (AIS >= 3) and positive BAC (OR 2.34, 95% CI 1.096-5.001) were
      identified as strongest independent predictors for head CT. CONCLUSION: Alcohol
      intoxication is a common finding in trauma patients, and the rate of moderate and
      serious head injuries seems to be comparable to a more severely injured control
      group. Furthermore, head CT utilization in intoxicated patients is associated
      with significant radiation exposure, despite poor image quality, due to motion
      artifacts (27%). Future strategies are required to exclude head injuries safely,
      while reducing the rate of head CT and associated radiation exposure in
      intoxicated patients.

PMID- 29569000
TI  - The Influence of Internalized Stigma on the Efficacy of an HIV Prevention and
      Relationship Education Program for Young Male Couples.
AB  - Young MSM are at increased risk for HIV, especially in the context of serious
      relationships, but there is a lack of couples-based HIV prevention for this
      population. The 2GETHER intervention-an HIV prevention and relationship education
      program for young male couples-demonstrated promising effects in a pilot trial.
      However, there is evidence that internalized stigma (IS) can influence treatment
      outcomes among MSM. The current study examined the influence of IS on the
      efficacy of the 2GETHER intervention among 57 young male couples. The
      intervention led to decreases in percentage of condomless anal sex partners and
      increases in subjective norms regarding HIV prevention for those with low/average
      IS, but not high IS. The intervention also led to increases in motivation to get
      tested with one's partner and decreases in alcohol consumption for those with
      high IS, but not low/average IS. In contrast, IS did not moderate intervention
      effects on other motivational constructs, dyadic adjustment, or alcohol problems.
      In sum, IS influences the extent to which young male couples benefit from HIV
      prevention and relationship education depending on the outcome. Research is
      needed to understand how IS influences treatment outcomes.

PMID- 29569002
TI  - Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical
      and Experimental Evidence.
AB  - BACKGROUND: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each
      year and can induce chagasic megacolon. Little is known about how serotonin (5
      HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters
      T. cruzi infection in the colon. MATERIALS AND METHODS: Forty-eight paraffin
      embedded samples from normal colon and chagasic megacolon were
      histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout
      (KO) mice and c-KitW-sh mice underwent T. cruzi infection together with their
      wild-type counterparts. Also, mice underwent different drug treatments
      (16.1.1064.60.3). RESULTS: In both humans and experimental mouse models, the
      serotonergic system was activated by T. cruzi infection (p < 0.05). While
      treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the
      colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T.
      cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory
      signaling, but also to enlarge the pericryptal macrophage and mast cell
      populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p <
      0.01), although it did not further alter the neuroendocrine cell number and Tph1
      expression (p > 0.05). Further experimentation revealed that pharmacologically
      inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar
      finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p >
      0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic
      trypanosomiasis (p < 0.01). CONCLUSION: We show that mast cells may modulate the
      T. cruzi-related increase of 5-HT synthesis in the intestinal colon.

PMID- 29569003
TI  - Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric
      Patients with Autoimmune Hepatitis.
AB  - BACKGROUND: We studied the efficacy and safety of mycophenolate mofetil (MMF) and
      tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis
      (AIH) who were intolerant or non-responders to standard therapy (corticosteroid
      and azathioprine). PATIENTS AND METHODS: We performed a retrospective study of
      data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18
      years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a
      median of 72 months (range 8-182) were evaluated. Patients were categorized into
      two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine,
      and group 2 (n = 21) were non-responders to standard therapy. RESULTS: Overall
      complete response rates were similar in patients treated with MMF and tacrolimus
      (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a
      biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929).
      More patients in group 2 given tacrolimus compared to MMF had a complete
      response, but the difference was not statistically significant (50.0 vs. 22.2%, p
      = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by
      tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF
      and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006).
      Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed
      side effects that led to therapy withdrawal. CONCLUSIONS: Long-term therapy with
      MMF or tacrolimus was generally well tolerated by pediatric patients with AIH.
      Both MMF and tacrolimus had excellent efficacy in patients intolerant to
      corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in
      patients failing previous therapy.

PMID- 29569004
TI  - [Manifestation of eosinophilic granulomatosis with polyangiitis in the head and
      neck area over time taking systemic disease activity into consideration].
AB  - BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare
      granulomatous vasculitis of the small and medium sized blood vessels of unknown
      etiology. A regular involvement of the head and neck area is known. Since it is
      not yet known whether the inflammatory processes in the head and neck area are
      parallel to the systemic disease activity, the course of systemic and local
      disease activity was investigated in a comparative study. MATERIAL AND METHODS:
      Between 1990 and 2010 the disease progression of 25 patients with a total of 90
      consultations and an average observation period of 7.02 years was recorded. The
      anamnesis, clinical observation and testing were performed in order to describe
      ear nose and throat (ENT) manifestations. Moreover, systemic data, such as the
      Birmingham Vasculitis Activity Score (BVAS), the Vasculitis Damage Index (VDI)
      and the serological parameters C-reactive protein (CRP), eosinophilic cationic
      protein (ECP) and absolute eosinophil count (EOS) were collected. In order to
      define the activity in the head and neck area the existing manifestations were
      summarized and statistically compared to the systemic data using Spearman's rank
      correlation coefficient. RESULTS: Overall the statistical analysis showed a very
      weak correlation between the disease activity in the ENT area and systemic
      disease activity, which is not considered as significant. Comparing activity in
      the nose region to systemic activity, significant values were found in 22.9% of
      all consultations. Comparing activity in the ear region to systemic activity,
      11.8% of all consultations showed significant values. CONCLUSION: The results
      indicate that the disease activity in the head and neck area is independent of
      the systemic activity. Moreover, they point out a potential independent
      autoimmune inflammatory process in the mentioned regions; therefore, treatment
      should include long-term follow-up and an interdisciplinary management.

PMID- 29569005
TI  - Impact of Post-Discharge Disposition on Risk and Causes of Readmission Following
      Liver and Pancreas Surgery.
AB  - BACKGROUND: The relationship between the post-discharge settings and the risk of
      readmission has not been well examined. We sought to identify the association
      between discharge destinations and readmission rates after liver and pancreas
      surgery. METHODS: The 2013-2015 Medicare-Provider Analysis and Review (MEDPAR)
      database was reviewed to identify liver and pancreas surgical patients. Patients
      were subdivided into three groups based on discharge destination: home/self-care
      (HSC), home with home health assistance (HHA), and skilled nursing facility
      (SNF). The association between post-acute settings, readmission rates, and
      readmission causes was assessed. RESULTS: Among 15,141 liver or pancreas surgical
      patients, 60% (n = 9046) were HSC, 26.9% (n = 4071) were HHA, and 13.4% (n =
      2024) were SNF. Older, female patients and patients with >= 2 comorbidities, >= 2
      previous admissions, an emergent index admission, an index complication, and >= 5
      day length of stay were more likely to be discharged to HHA or SNF compared to
      HSC (all P < 0.001). Compared to HSC, HHA and SNF patients had a 34 and a 67%
      higher likelihood of 30-day readmission, respectively. The HHA and SNF settings
      were also associated with a 33 and a 69% higher risk of 90-day readmission. There
      was no association between discharge destination and readmission causes.
      CONCLUSION: Among liver and pancreas surgical patients, HHA and SNF patients had
      a higher risk of readmission within 30 and 90 days. There was no difference in
      readmission causes and discharge settings. The association between discharge
      setting and the higher risk of readmission should be further evaluated as the
      healthcare system seeks to reduce readmission rates after surgery.

PMID- 29569006
TI  - Contemporary Management of Sigmoid Volvulus.
AB  - BACKGROUND: Sigmoid volvulus is an uncommon cause of bowel obstruction that is
      historically associated with high morbidity and mortality. The objective of this
      study was to evaluate contemporary management of sigmoid volvulus and the safety
      of primary anastomosis in patients with sigmoid volvulus. METHODS: The National
      Surgical Quality Improvement Project from 2012 to 2015 was queried for patients
      with colonic volvulus who underwent left-sided colonic resection. A propensity
      score-matched analysis was performed to compare patients with sigmoid volvulus
      undergoing colectomy with primary anastomosis without proximal diversion to
      colectomy with end colostomy. RESULTS: Two thousand five hundred thirty-eight
      patients with sigmoid volvulus were included for analysis. Patients had a median
      age of 68 years (interquartile range, 55-80) and 79% were fully independent
      preoperatively. Fifty-one percent of operations were performed emergently. One
      thousand eight hundred thirteen (71%) patients underwent colectomy with
      anastomosis, 240 (10%) colectomy with anastomosis and proximal diversion, and 485
      (19%) colectomy with end colostomy. Overall, 30-day mortality and morbidity were
      5 and 40%, respectively. After propensity score matching, mortality, overall
      morbidity, and serious morbidity were similar between groups. CONCLUSIONS:
      Sigmoid volvulus occurs in elderly and debilitated patients with significant
      morbidity, mortality, and lifestyle implications. In selected patients,
      anastomosis without proximal diversion in patients with sigmoid volvulus results
      in similar outcomes to colectomy with end colostomy.

PMID- 29569007
TI  - Associations between fruit and vegetables intake and abnormal glucose tolerance
      among women with prior gestational diabetes mellitus.
AB  - PURPOSE: Women with prior gestational diabetes mellitus (GDM) are at higher risk
      of type 2 diabetes (T2D). The aim of this study was to investigate the
      association between fruit and vegetables (FV) intake and abnormal glucose
      tolerance (AGT) among women with prior GDM. METHODS: A total of 281 women with
      prior GDM have been recruited a mean of 6 years after their pregnancy in this
      cohort study. FV intake was obtained with a validated food frequency
      questionnaire (FFQ). Anthropometric and glycemic components were measured during
      their clinical visit and women were stratified according to normal glucose
      tolerance (NGT) or AGT. RESULTS: A cross-sectional analysis showed that a total
      of 155 women had NGT and 126 AGT. Women with AGT had significantly lower FV (6.5
      +/- 0.2) and vegetables servings (3.9 +/- 0.2) and tended to have lower fruit
      servings (2.6 +/- 0.2) than women with NGT (7.4 +/- 0.2, 4.5 +/- 0.2 and 3.0 +/-
      0.1, respectively) (p = 0.001, p = 0.04 and p = 0.10, respectively, adjusted for
      age and BMI). FV intake, per one serving increase, was associated with a reduced
      likelihood of having AGT [OR = 0.88 (0.81-0.97) after adjustment for age and
      BMI]. Vegetables or fruit intake tended to be associated with a reduced
      likelihood of having AGT [OR = 0.88 (0.78-1.00) and OR = 0.88 (0.76-1.02),
      respectively, after adjustment for age and BMI]. CONCLUSIONS: Higher intake of FV
      may be associated with a lower likelihood of AGT among women with prior GDM.
      Further studies are needed to confirm these results in this high-risk population.

PMID- 29569008
TI  - Dopamine receptors in the rat entopeduncular nucleus.
AB  - Dopamine is critical for the normal functioning of the basal ganglia, modulating
      both input and output nuclei of this system. The distribution and function of
      each of the five dopamine receptor subtypes have been studied extensively in the
      striatum. However, the role of extrastriatal dopamine receptors in basal ganglia
      information processing is less clear. Here, we studied the anatomical
      distribution of dopamine receptors in one of the output nuclei of the rodent
      basal ganglia, the entopeduncular nucleus (EP). The presence of all dopamine
      receptor subtypes was verified in the EP using immunostaining. We detected co
      localization of dopamine receptors with VGAT, which suggests presynaptic
      expression on GABAergic terminals. D1R and D2R were strongly colocalized with
      VGAT, whereas DR3-5 showed only sparse co-localization. We further labeled
      striatal or pallidal neurons with GFP and showed that only D1 receptors were co
      localized with striatal terminals, while only D2R and D3R were co-localized with
      pallidal terminals. Dopamine receptors were also strongly co-localized with MAP2,
      indicating postsynaptic expression. Overall, these findings suggest that the
      dopaminergic system modulates activity in the EP both directly via postsynaptic
      receptors, and indirectly via GABAergic synapses stemming from the direct and
      indirect pathways.

PMID- 29569010
TI  - Posterior Circulation Occlusions May Be Associated with Distal Emboli During
      Thrombectomy : Factors for Distal Embolization and a Review of the Literature.
AB  - BACKGROUND: Distal embolization or movement of the thrombus to previously
      uninvolved vasculature are feared complications during stroke thrombectomy. We
      looked at associated factors in a consecutive series of patients who underwent
      thrombectomy with the same endovascular device. METHODS: We included all patients
      with acute ischemic stroke in the anterior or posterior circulation, who
      underwent thrombectomy with the same thrombectomy device for acute stroke from
      2013 to 2016. Distal embolization was defined as any movement of the thrombus
      into a previously uninvolved portion of the cerebral vasculature or the presence
      of thrombotic material further downstream in the affected vessel, which occurred
      after the initial angiogram. We studied patient-related as well as technical
      factors to determine their association with distal emboli. RESULTS: In this study
      167 consecutive acute stroke patients treated with the emboTrap(r) device
      (Cerenovus, Irvine, CA, USA) were included with a median National Institutes of
      Health Stroke Scale (NIHSS) of 15 (range 2-30) and mean age of 67 years (SD 13.1
      years). Of the patients in our cohort 20 (11.9%) experienced distal emboli, with
      2.3% into a new territory and 9.6% into a territory distal to the primary
      occlusion. On univariate analysis, age, intravenous tissue plasminogen activator
      (tPA), posterior circulation occlusions, and general anesthesia were associated
      with distal emboli. On multivariate analysis, only posterior circulation
      occlusions (odds ratio OR 4.506 95% confidence interval CI 1.483-13.692, p =
      0.008) were significantly associated with distal emboli. Distal embolization was
      not significantly associated with worse functional outcomes at 3 months,
      increased mortality or increased bleeding risk. CONCLUSION: Posterior circulation
      occlusions were significantly associated with distal emboli during thrombectomy,
      possibly due to the lack of flow arrest during such procedures. New techniques
      and devices should be developed to protect against embolic complications during
      posterior circulation stroke thrombectomy.

PMID- 29569009
TI  - Paraventricular hypothalamic and amygdalar CRF neurons synapse in the external
      globus pallidus.
AB  - Stress evokes directed movement to escape or hide from potential danger.
      Corticotropin-releasing factor (CRF) neurons are highly activated by stress;
      however, it remains unclear how this activity participates in stress-evoked
      movement. The external globus pallidus (GPe) expresses high levels of the primary
      receptor for CRF, CRFR1, suggesting the GPe may serve as an entry point for
      stress-relevant information to reach basal ganglia circuits, which ultimately
      gate motor output. Indeed, projections from CRF neurons are present within the
      GPe, making direct contact with CRFR1-positive neurons. CRFR1 expression is
      heterogenous in the GPe; prototypic GPe neurons selectively express CRFR1, while
      arkypallidal neurons do not. Moreover, CRFR1-positive GPe neurons are excited by
      CRF via activation of CRFR1, while nearby CRFR1-negative neurons do not respond
      to CRF. Using monosynaptic rabies viral tracing techniques, we show that CRF
      neurons in the stress-activated paraventricular nucleus of the hypothalamus
      (PVN), central nucleus of the amygdala (CeA), and bed nucleus of the stria
      terminalis (BST) make synaptic connections with CRFR1-positive neurons in the GPe
      an unprecedented circuit connecting the limbic system with the basal ganglia. CRF
      neurons also make synapses on Npas1 neurons, although the majority of Npas1
      neurons are arkypallidal and do not express CRFR1. Interestingly, prototypic and
      arkypallidal neurons receive different patterns of innervation from CRF-rich
      nuclei. Hypothalamic CRF neurons preferentially target prototypic neurons, while
      amygdalar CRF neurons preferentially target arkypallidal neurons, suggesting that
      these two inputs to the GPe may have different impacts on GPe output. Together,
      these data describe a novel neural circuit by which stress-relevant information
      carried by the limbic system signals in the GPe via CRF to influence motor
      output.

PMID- 29569013
TI  - Prevention of Contrast and Radiation Injury During Coronary Angiography and
      Percutaneous Coronary Intervention.
AB  - PURPOSE OF REVIEW: In this review, we provide a summary of the recently published
      literature on various methods of preventing contrast-induced acute kidney injury
      (CI-AKI) and radiation-related injuries associated with cardiac catheterization
      and percutaneous coronary intervention (PCI). RECENT FINDINGS: The overall
      reported incidence of CI-AKI is declining, primarily due to adaptation of a
      standardized definition for CI-AKI as well as implementation of pre-procedural
      protocols to prevent or decrease the risk of CI-AKI. The implementation of
      increasing awareness and establishing radiation protection culture has been shown
      to be effective measures in reducing radiation exposure. Coronary angiography and
      PCI are valuable diagnostic and therapeutic tools in cardiovascular medicine.
      Accurate imaging of the coronary arteries in cardiac catheterization is dependent
      on the use of intravascular injection of iodinated contrast media and
      fluoroscopic imaging. Patients undergoing diagnostic and interventional cardiac
      catheterization may be exposed to a substantial amount of contrast media and
      ionizing radiation. Administration of contrast media is correlated with increased
      risk of CI-AKI, and exposure to radiation is known to be associated with a
      spectrum of acute and chronic tissue injuries.

PMID- 29569014
TI  - Do country-specific preference weights matter in the choice of mapping
      algorithms? The case of mapping the Diabetes-39 onto eight country-specific EQ-5D
      5L value sets.
AB  - PURPOSE: To develop mapping algorithms that transform Diabetes-39 (D-39) scores
      onto EQ-5D-5L utility values for each of eight recently published country
      specific EQ-5D-5L value sets, and to compare mapping functions across the EQ-5D
      5L value sets. METHODS: Data include 924 individuals with self-reported diabetes
      from six countries. The D-39 dimensions, age and gender were used as potential
      predictors for EQ-5D-5L utilities, which were scored using value sets from eight
      countries (England, Netherland, Spain, Canada, Uruguay, China, Japan and Korea).
      Ordinary least squares, generalised linear model, beta binomial regression,
      fractional regression, MM estimation and censored least absolute deviation were
      used to estimate the mapping algorithms. The optimal algorithm for each country
      specific value set was primarily selected based on normalised root mean square
      error (NRMSE), normalised mean absolute error (NMAE) and adjusted-r2. Cross
      validation with fivefold approach was conducted to test the generalizability of
      each model. RESULTS: The fractional regression model with loglog as a link
      function consistently performed best in all country-specific value sets. For
      instance, the NRMSE (0.1282) and NMAE (0.0914) were the lowest, while adjusted-r2
      was the highest (52.5%) when the English value set was considered. Among D-39
      dimensions, the energy and mobility was the only one that was consistently
      significant for all models. CONCLUSIONS: The D-39 can be mapped onto the EQ-5D-5L
      utilities with good predictive accuracy. The fractional regression model, which
      is appropriate for handling bounded outcomes, outperformed other candidate
      methods in all country-specific value sets. However, the regression coefficients
      differed reflecting preference heterogeneity across countries.

PMID- 29569015
TI  - Psychometric properties of the Chinese version of resilience scale specific to
      cancer: an item response theory analysis.
AB  - OBJECTIVE: Classic theory test has been used to develop and validate the 25-item
      Resilience Scale Specific to Cancer (RS-SC) in Chinese patients with cancer. This
      study was designed to provide additional information about the discriminative
      value of the individual items tested with an item response theory analysis.
      METHODS: A two-parameter graded response model was performed to examine whether
      any of the items of the RS-SC exhibited problems with the ordering and steps of
      thresholds, as well as the ability of items to discriminate patients with
      different resilience levels using item characteristic curves. RESULTS: A sample
      of 214 Chinese patients with cancer diagnosis was analyzed. The established three
      dimension structure of the RS-SC was confirmed. Several items showed problematic
      thresholds or discrimination ability and require further revision. CONCLUSIONS:
      Some problematic items should be refined and a short-form of RS-SC maybe feasible
      in clinical settings in order to reduce burden on patients. However, the
      generalizability of these findings warrants further investigations.

PMID- 29569016
TI  - PROMIS(r)-29 v2.0 profile physical and mental health summary scores.
AB  - PURPOSE: The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10
      numeric rating item and seven health domains (physical function, fatigue, pain
      interference, depressive symptoms, anxiety, ability to participate in social
      roles and activities, and sleep disturbance) using four items per domain. This
      paper describes the development of physical and mental health summary scores for
      the PROMIS-29 v2.0. METHOD: We conducted factor analyses of PROMIS-29 scales on
      data collected from two internet panels (n = 3000 and 2000). RESULTS:
      Confirmatory factor analyses provided support for a physical health factor
      defined by physical function, pain (interference and intensity), and ability to
      participate in social roles and activities, and a mental health factor defined
      primarily by emotional distress (anxiety and depressive symptoms). Reliabilities
      for these two summary scores were 0.98 (physical health) and 0.97 (mental
      health). Correlations of the PROMIS-29 v2.0 physical and mental health summary
      scores with chronic conditions and other health-related quality of life measures
      were consistent with a priori hypotheses. CONCLUSIONS: This study develops and
      provides preliminary evidence supporting the reliability and validity of PROMIS
      29 v2.0 physical and mental health summary scores that can be used in future
      studies to assess impacts of health care interventions and track changes in
      health over time. Further evaluation of these and alternative summary measures is
      recommended.

PMID- 29569017
TI  - A review of preference-based measures for the assessment of quality of life in
      children and adolescents with cerebral palsy.
AB  - PURPOSE: To examine the psychometric properties and suitability for use within
      the context of cerebral palsy research in children and adolescents of generic
      preference-based outcome measures (PROMs). METHODS: Nine electronic databases
      were searched in this systematic review. The consensus-based standards for the
      selection of health measurement instruments (COSMIN) checklist were used to
      measure the psychometric properties of the PROMs. A meta-analysis was used to
      pool correlation coefficients for convergent validity using the Schmidt-Hunter
      method. Heterogeneity was assessed using the I-squared statistic (I2). RESULTS:
      Four preference-based PROMs were identified from eight studies: Health Utilities
      Index-Mark 2 and 3 (HUI-2 and HUI-3, respectively), the Assessment Quality of
      Life-4 dimension (AQoL-4D) and the EuroQol-5 dimension 3 level (EQ-5D-3L). Only
      the HUI system was primarily developed for application with children/adolescents
      though health-state values for scoring the PROM were elicited from adults. The
      HUI-3 covered the most relevant constructs though it excludes important modules
      of health-related quality of life (HRQOL) such as activity limitations and
      participation restrictions. In terms of psychometric properties, evidence was
      presented for only five of COSMIN measurement properties: reliability (HUI3),
      measurement error (HUI-3), content validity (HUI-2 and HUI-3), Hypotheses testing
      (HUI-3 and AQoL-4D) and criterion validity (HUI-3). No papers reported on
      internal consistency, structural validity, cross-cultural validity or
      responsiveness of the preference-based measures in children and adolescents with
      cerebral palsy. CONCLUSIONS: This review highlights the dearth in studies using
      preference-based PROMs to measure HRQOL associated with cerebral palsy in
      children and adolescents. The HUI-3 demonstrated the strongest psychometric
      properties, though it does not cover all dimensions relevant to this population.

PMID- 29569018
TI  - Breast cancer survival, survival disparities, and guideline-based treatment.
AB  - PURPOSE: The role of appropriate therapy in breast cancer survival and survival
      disparities by race/ethnicity has not been fully elucidated. We investigated
      whether lack of guideline-recommended therapy contributed to survival differences
      overall and among Hispanics relative to non-Hispanic white (NHW) women in a case
      cohort study. METHODS: The study included a 15% random sample of female invasive
      breast cancer patients diagnosed from 1997 to 2009 in 6 New Mexico counties and
      all deaths due to breast cancer-related causes. Information was obtained from
      comprehensive medical chart reviews. National Comprehensive Cancer Network
      (NCCN(r)) guideline-recommended treatment was assessed among white women aged <
      70 who were free of contraindications for recommended therapy, had stage I-III
      tumors, and survived >= 12 months. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) for breast cancer death were estimated using Cox proportional
      hazards models. RESULTS: Included women represented 4635 patients and 449 breast
      cancer deaths. Women who did not receive radiotherapy (HR 2.3; 95% CI 1.2-4.4) or
      endocrine therapy (HR 2.0; 95% CI 1.0-4.0) as recommended by guidelines had an
      increased risk of breast cancer death, relative to those treated appropriately.
      Receipt of guideline-recommended therapy did not differ between Hispanic and NHW
      women for chemotherapy (84.2% vs. 81.3%, respectively), radiotherapy (89.2% vs.
      91.1%), or endocrine therapy (89.2% vs. 85.8%), thus did not influence Hispanic
      survival disparities. CONCLUSIONS: Lack of guideline-recommended radiotherapy or
      endocrine therapy contributed to survival as strongly as other established
      prognostic indicators. Hispanic survival disparities in this population do not
      appear to be attributable to treatment differences.

PMID- 29569019
TI  - Prediction of breast cancer risk with volatile biomarkers in breath.
AB  - BACKGROUND: Human breath contains volatile organic compounds (VOCs) that are
      biomarkers of breast cancer. We investigated the positive and negative predictive
      values (PPV and NPV) of breath VOC biomarkers as indicators of breast cancer
      risk. METHODS: We employed ultra-clean breath collection balloons to collect
      breath samples from 54 women with biopsy-proven breast cancer and 124 cancer-free
      controls. Breath VOCs were analyzed with gas chromatography (GC) combined with
      either mass spectrometry (GC MS) or surface acoustic wave detection (GC SAW).
      Chromatograms were randomly assigned to a training set or a validation set. Monte
      Carlo analysis identified significant breath VOC biomarkers of breast cancer in
      the training set, and these biomarkers were incorporated into a multivariate
      algorithm to predict disease in the validation set. In the unsplit dataset, the
      predictive algorithms generated discriminant function (DF) values that varied
      with sensitivity, specificity, PPV and NPV. RESULTS: Using GC MS, test accuracy =
      90% (area under curve of receiver operating characteristic in unsplit dataset)
      and cross-validated accuracy = 77%. Using GC SAW, test accuracy = 86% and cross
      validated accuracy = 74%. With both assays, a low DF value was associated with a
      low risk of breast cancer (NPV > 99.9%). A high DF value was associated with a
      high risk of breast cancer and PPV rising to 100%. CONCLUSION: Analysis of breath
      VOC samples collected with ultra-clean balloons detected biomarkers that
      accurately predicted risk of breast cancer.

PMID- 29569020
TI  - Potentially toxic elements in soil of the Khyber Pakhtunkhwa province and Tribal
      areas, Pakistan: evaluation for human and ecological risk assessment.
AB  - Potentially toxic elements (PTEs) contaminations in the soil ecosystem are
      considered as extremely hazardous due to toxicity, persistence and
      bioaccumulative nature. Therefore, this study was aimed to summarize the results
      of published PTEs in soil of Khyber Pakhtunkhwa and Tribal areas, Pakistan.
      Results were evaluated for the pollution quantification factors, including
      contamination factor (CF), pollution load index (PLI), ecological risk index
      (ERI) and human health risk assessment. The highest CF (797) and PLI (7.35)
      values were observed for Fe and ERI (857) values for Cd. Soil PTEs concentrations
      were used to calculate the human exposure for the risk assessment, including
      chronic or non-carcinogenic risks such as the hazard quotient (HQ) and
      carcinogenic or cancer risk (CR). The values of HQ were > 1 for the Cd, Co and Cr
      in Khyber Pakhtunkhwa and Tribal areas. Tribal areas showed higher values of ERI,
      HQ, and CR as compared to the Khyber Pakhtunkhwa that were attributed to the
      mining activities, weathering and erosion of mafic and ultramafic bedrocks
      hosting ophiolites. This study strongly recommends that best control measures
      need to be taken for soil PTEs with the intent to alleviate any continuing
      potential threat to the human health, property and environment, which otherwise
      could enter ecosystem and ultimately the living beings. Further studies are
      recommended to combat the soil PTEs concentrations and toxicity in the Tribal
      areas for a best picture of understanding the element effects on human, and
      environment can be achieved that will lead to a sustainable ecological harmony.

PMID- 29569021
TI  - Assessing oral health-related quality of life in children and adolescents: a
      systematic review and standardized comparison of available instruments.
AB  - OBJECTIVES: To obtain a systematic and standardized evaluation of the current
      evidence on development process, metric properties, and administration issues of
      oral health-related quality of life instruments available for children and
      adolescents. MATERIALS AND METHODS: A systematic search until October 2016 was
      conducted in PubMed, Embase, Lilacs, SciELO, and Cochrane databases. Articles
      with information regarding the development process, metric properties, and
      administration issues of pediatric instruments measuring oral health-related
      quality of life were eligible for inclusion. Two researchers independently
      evaluated each instrument applying the Evaluating Measures of Patient-Reported
      Outcomes (EMPRO) tool. An overall and seven attribute-specific EMPRO scores were
      calculated (range 0-100, worst to best): measurement model, reliability,
      validity, responsiveness, interpretability, burden, and alternative forms.
      RESULTS: We identified 18 instruments evaluated in 132 articles. From five
      instruments designed for preschoolers, the Early Childhood Oral Health Impact
      Scale (ECOHIS) obtained the highest overall EMPRO score (82.2). Of nine
      identified for schoolchildren and adolescents, the best rated instrument was the
      Child Perceptions Questionnaire 11-14 (82.1). Among the four instruments
      developed for any age, the Family Impact Scale (FIS) obtained the highest scores
      (80.3). CONCLUSION: The evidence supports the use of the ECOHIS for preschoolers,
      while the age is a key factor when choosing among the four recommended
      instruments for schoolchildren and adolescents. Instruments for specific
      conditions, symptoms, or treatments need further research on metric properties.
      CLINICAL RELEVANCE: Our results facilitate decision-making on the correct oral
      health-related quality of life instrument selection for any certain study purpose
      and population during the childhood and adolescence life cycle.

PMID- 29569022
TI  - Professionals' views on the development process of a structural collaboration
      between child and adolescent psychiatry and child welfare: an exploration through
      the lens of the life cycle model.
AB  - This study, as a part of a participatory action research project, reports the
      development process of an innovative collaboration between child and adolescent
      psychiatry and child welfare, for adolescent girls with multiple and complex
      needs. The findings emerge from a qualitative descriptive analysis of four focus
      groups with 30 professionals closely involved in this project, and describe the
      evolution of the collaborative efforts and outcomes through time. Participants
      describe large investments and negative consequences of rapid organizational
      change in the beginning of the collaboration project, while benefits of the
      intensive collaboration only appeared later. A shared person-centred vision and
      enhanced professionals' confidence were pointed out as important contributors in
      the evolution of the collaboration. Findings were compared to the literature and
      showed significant analogy with the life cycle model for shared service centres
      that describe the maturation of collaborations from a management perspective.
      These findings enrich the knowledge about the development process of
      collaboration in health and social care. In increasingly collaborative services,
      child and adolescent psychiatrists and policy makers should be aware that gains
      from a collaboration will possibly only be achieved in the longer term, and
      benefit from knowing which factors have an influence on the evolution of a
      collaboration project.

PMID- 29569023
TI  - Current perspectives on in vitro maturation and its effects on oocyte genetic and
      epigenetic profiles.
AB  - In vitro maturation (IVM), the maturation in culture of immature oocytes, has
      been used in clinic for more than 20 years. Although IVM has the specific
      advantages of low cost and minor side effects over controlled ovarian
      stimulation, the prevalence of IVM is less than 1% of routine in vitro
      fertilization and embryo transfer techniques in many reproductive centers. In
      this review, we searched the MEDLINE database for all full texts and/or abstract
      articles published in English with content related to oocyte IVM mainly between
      2000 and 2016. Many different aspects of the IVM method may influence oocyte
      potential, including priming, gonadotrophin, growth factors, and culture times.
      The culture conditions of IVM result in alterations in the oocyte or cumulus cell
      transcriptome that are not observed under in vivo culture conditions.
      Additionally, epigenetic modifications, such as DNA methylation or acetylation,
      are also different between in vitro and in vivo cultured oocytes. In sum, current
      IVM technique is still not popular and requires more systematic and intensive
      research to improve its effects and applications. This review will help point our
      problems, supply evidence or clues for future improving IVM technique, thus
      assist patients for fertility treatment or preservation as an additional option.

PMID- 29569024
TI  - Soluble Fibrin Monomer Complex and Prediction of Cardiovascular Events in Atrial
      Fibrillation: The Observational Murcia Atrial Fibrillation Project.
AB  - BACKGROUND: Soluble fibrin monomer complex (SFMC) is a biomarker of fibrin
      formation abnormally elevated in clinical situations of hypercoagulability.
      OBJECTIVE: We investigated the association and predictive performance of SFMC for
      stroke, adverse cardiovascular events, cardiovascular mortality and all-cause
      mortality in a cohort of patients with atrial fibrillation (AF) receiving vitamin
      K antagonist (VKA) anticoagulant therapy. DESIGN: During the second semester of
      2007, we included 1226 AF outpatients stable on VKAs (INR 2.0-3.0) over a period
      of 6 months. SFMC levels were assessed at baseline. During 6.5 (IQR 4.4-8.0)
      years of follow-up, we recorded all ischemic strokes, adverse cardiovascular
      events (composite of stroke, acute heart failure, acute coronary syndrome and
      cardiovascular death), cardiovascular deaths and all-cause deaths. PARTICIPANTS:
      All patients were recruited consecutively. We excluded patients with rheumatic
      mitral valves, prosthetic heart valves, acute coronary syndrome, stroke,
      hemodynamic instability, hospital admissions or surgical interventions within the
      preceding 6 months. MAIN MEASURES: SFMC levels were measured in plasma by
      immunoturbidimetry in an automated coagulometer (STALiatestFM, Diagnostica Stago,
      Asnieres, France). KEY RESULTS: We recorded 121 (1.52%/year) ischemic strokes,
      257 (3.23%/year) cardiovascular events, 67 (0.84%/year) cardiovascular deaths and
      486 (6.10%/year) all-cause deaths. SFMC >12 MUg/mL was not associated with stroke
      but was associated with higher risk of cardiovascular events (HR 1.72, 95% CI
      1.31-2.26), cardiovascular mortality (HR 2.16, 95% CI 1.30-3.57) and all-cause
      mortality (HR 1.26, 95% CI 1.03-1.55). When SFMC >12 MUg/mL was added to the
      CHA2DS2-VASc, there were significant improvements in predictive performance,
      sensitivity and reclassification for adverse cardiovascular events (c-index:
      0.645 vs. 0.660, p = 0.010; IDI = 0.013, p < 0.001; NRI = 0.121, p < 0.001) and
      cardiovascular mortality (c-index: 0.661 vs. 0.691, p = 0.006; IDI = 0.009, p =
      0.049; NRI = 0.217, p < 0.001), but decision curves demonstrated a similar net
      benefit and clinical usefulness. CONCLUSIONS: In AF patients taking VKAs, high
      SFMC levels were associated with the risk of adverse cardiovascular events,
      cardiovascular mortality and all-cause mortality. The addition of SFMC to the
      CHA2DS2-VASc score improved its predictive performance for these outcomes, but
      failed to show an improvement in clinical usefulness.

PMID- 29569025
TI  - [Simultaneous fracture of the acromion and coracoid process : Rare variant of
      double disruption of the superior shoulder suspensory complex].
AB  - INTRODUCTION: Simultaneous fracture of the acromion and coracoid process
      represents a double disruption of the superior shoulder suspensory complex
      (SSSC). To date, the two largest reported series have comprised five and eight
      cases. The aim of this study was to investigate the functional outcome in
      patients who sustained this rare injury and to provide a review of the relevant
      literature. MATERIAL AND METHODS: In this retrospective study, patients who were
      surgically treated between 2009 and 2014 were identified from medical records and
      the patients were asked to attend a follow-up examination. Functional results,
      measured as the Constant score and Disabilities of the Arm, Shoulder and Hand
      (DASH) score, were the main outcomes of the study. RESULTS: A total of six
      patients underwent surgery for this type of double disruption of the SSSC. All
      but one patient suffered a high-impact trauma with other associated injuries. The
      coracoid fracture was classified as type I according to Ogawa in all cases, and
      the acromion fracture was type III according to Kuhn in 5 out of 6 cases. At
      least one of the fracture sites was stabilized. Of the patients one showed a
      concurrent lateral clavicle fracture, representing a third disruption of the
      SSSC, and another had a fracture of the medial third of the clavicle,
      representing a strut fracture. In these cases, two fracture sites were operated
      on. At an average follow-up period of 47 months all but one fracture had healed.
      In one patient, asymptomatic non-union of the acromion was found. The average
      DASH score was 22 points and the average Constant score was 74 points.
      CONCLUSION: This rare injury pattern is usually caused by high-impact trauma, and
      concomitant injuries frequently occur. Nevertheless, surgical stabilization of at
      least one of the fracture sites showed satisfactory functional results.

PMID- 29569027
TI  - Polymeric nanoparticles for topical delivery of alpha and beta arbutin:
      preparation and characterization.
AB  - To investigate the use of chitosan nanoparticles (CS-TPP-NPs) as carriers for
      alpha- and beta-arbutin. In this study, CS-TPP-NPs containing alpha- and beta
      arbutin were prepared via the ionic cross-linking of CS and TPP and characterized
      for particle size, zeta potential, and dispersity index. The entrapment
      efficiency and loading capacity of various beta-arbutin concentrations (0.1, 0.2,
      0.4, 0.5, and 0.6%) were also investigated. SEM, TEM FTIR, DSC and TGA analyses
      of the nanoparticles were performed to further characterize the nanoparticles.
      Finally, stability and release studies were undertaken to ascertain further the
      suitability of the nanoparticles as a carrier system for alpha- and beta-arbutin.
      Data obtained clearly indicates the potential for use of CS-TPP-NPs as a carrier
      for the delivery of alpha- and beta-arbutin. The size obtained for the alpha
      nanoparticles (alpha-arbutin CSNPs) ranges from 147 to 274 d.nm, with an increase
      in size with increasing alpha arbutin concentration. beta-arbutin nanoparticles
      (beta-arbutin CSNPs) size range was from 211.1 to 284 dn.m. PdI for all
      nanoparticles remained between 0.2-0.3 while the zeta potential was between 41.6
      52.1 mV. The optimum encapsulation efficiency and loading capacity for 0.4% alpha
      arbutin CSNPs were 71 and 77%, respectively. As for beta-arbutin, CSNP optimum
      encapsulation efficiency and loading capacity for 0.4% concentration were 68 and
      74%, respectively. Scanning electron microscopy for alpha-arbutin CSNPs showed a
      more spherical shape compared to beta-arbutin CSNPs where rod-shaped particles
      were observed. However, under transmission electron microscopy, the shapes of
      both alpha- and beta-arbutin CSNP nanoparticles were spherical. The crystal phase
      identification of the studied samples was carried out using X-ray diffraction
      (XRD), and the XRD of both alpha and beta-arbutin CSNPs showed to be more
      crystalline in comparison to their free form. FTIR spectra showed intense
      characteristic peaks of chitosan appearing at 3438.3 cm-1 (-OH stretching), 2912
      cm-1 (-CH stretching), represented 1598.01 cm-1 (-NH2) for both nanoparticles.
      Stability studies conducted for 90 days revealed that both alpha- and beta
      arbutin CSNPs were stable in solution. Finally, release studies of both alpha-
      and beta-arbutin CSNPs showed a significantly higher percentage release in
      comparison to alpha- and beta-arbutin in their free form. Chitosan nanoparticles
      demonstrate considerable promise as a carrier system for alpha- and beta-arbutin,
      the use of which is anticipated to improve delivery of arbutin through the skin,
      in order to improve its efficacy as a whitening agent.

PMID- 29569028
TI  - Correction to: Perturbation Analysis of Indices of Lifespan Variability.
AB  - We discovered an error in Eq. (12) (p. 1621).

PMID- 29569029
TI  - A Second Look at the Process of Occupational Feminization and Pay Reduction in
      Occupations.
AB  - Using the IPUMS-USA data for the years 1960-2015, this study examines trends in
      the effect of occupational feminization on occupational pay in the U.S. labor
      market and explores some of the mechanisms underlying these trends. The findings
      show that the (negative) association between occupational feminization and
      occupational pay level has declined, becoming insignificent in 2015. This trend,
      however, is reversed after education is controlled for at the individual as well
      as the occupational level. The two opposite trends are discussed in light of the
      twofold effect of education: (1) the entry of women into occupations requiring
      high education, and (2) the growing returns to education and to occupations with
      higher educational requirements. These two processes have concealed the
      deterioration in occupational pay following feminization. The findings underscore
      the significance of structural forms of gender inequality in general, and
      occupational devaluation in particular.

PMID- 29569026
TI  - The Genetic Landscape of Hypoplastic Left Heart Syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) is one of the most lethal congenital heart
      defects, and remains clinically challenging. While surgical palliation allows
      most HLHS patients to survive their critical heart disease with a single
      ventricle physiology, many will suffer heart failure, requiring heart
      transplantation as the only therapeutic course. Current paradigm suggests HLHS is
      largely of hemodynamic origin, but recent findings from analysis of the first
      mouse model of HLHS showed intrinsic cardiomyocyte proliferation and
      differentiation defects underlying the left ventricular (LV) hypoplasia. The
      findings of similar defects of lesser severity in the right ventricle suggest
      this could contribute to the heart failure risks in surgically palliated HLHS
      patients. Analysis of 8 independent HLHS mouse lines showed HLHS is genetically
      heterogeneous and multigenic in etiology. Detailed analysis of the Ohia mouse
      line accompanied by validation studies in CRISPR gene-targeted mice revealed a
      digenic etiology for HLHS. Mutation in Sap130, a component of the HDAC repressor
      complex, was demonstrated to drive the LV hypoplasia, while mutation in Pcdha9, a
      protocadherin cell adhesion molecule played a pivotal role in the valvular
      defects associated with HLHS. Based on these findings, we propose a new paradigm
      in which complex CHD such as HLHS may arise in a modular fashion, mediated by
      multiple mutations. The finding of intrinsic cardiomyocyte defects would suggest
      hemodynamic intervention may not rescue LV growth. The profound genetic
      heterogeneity and oligogenic etiology indicated for HLHS would suggest that the
      genetic landscape of HLHS may be complex and more accessible in clinical studies
      built on a familial study design.

PMID- 29569030
TI  - Author Correction: Stem cells from human apical papilla decrease neuro
      inflammation and stimulate oligodendrocyte progenitor differentiation via activin
      A secretion.
AB  - In the original publication, sixth author's surname was incorrectly published as
      "Llyod" instead of "Lloyd". The correct name should read as "Amy Lloyd".

PMID- 29569031
TI  - Molecular characterization of medulloblastomas with extensive nodularity (MBEN).
AB  - Medulloblastoma with extensive nodularity (MBEN) is a rare histological variant
      of medulloblastoma (MB). These tumors are usually occurring in the first 3 years
      of life and are associated with good prognosis. Molecular analyses of MBEN,
      mostly limited to single cases or small series, have shown that they always
      classify as sonic hedgehog (SHH)-driven MB. Here, we have analyzed 25 MBEN
      through genome-wide DNA methylation, copy-number profiling and targeted next
      generation sequencing. Results of these analyses were compared with molecular
      profiles of other SHH MB histological variants. As expected, the vast majority of
      MBEN (23/25) disclosed SHH-associated epigenetic signatures and mutational
      landscapes but, surprisingly, two MBEN were classified as Group 3/4 MB. Most MBEN
      classified as SHH MB displayed SHH-related and mutually exclusive mutations in
      either SUFU, or PTCH1, or SMO at similar frequencies. However, only SUFU
      mutations were also identified in the germ-line. Most of SUFU-associated MBEN
      eventually recurred but patients were treated successfully with second-line high
      dose chemotherapy. Altogether, our data show that risk stratification even for
      well-recognizable histologies such as MBEN cannot rely on histology alone but
      should include additional molecular analyses such as methylation profiling and
      DNA sequencing. For all patients with "MBEN" histology, we recommend sequencing
      SUFU and PTCH1 in the tumor as well as in the germ-line for further clinical
      stratification and choice of the optimal treatment strategy upfront.

PMID- 29569032
TI  - 2D speckle-tracking TTE-based quantitative classification of left ventricular
      myocardium in patients with hypertrophic cardiomyopathy by the presence or the
      absence of fibrosis and/or hypertrophy.
AB  - We used peak longitudinal strain (PLS) on TTE in HCM patients to differentiate LV
      myocardium (LVM) into the following 4 groups: group 1-no fibrosis or hypertrophy
      (>= 13 mm), group 2-no fibrosis but hypertrophy evident, group 3-fibrosis present
      but without hypertrophy, and group 4-both fibrosis and hypertrophy. Seventeen HCM
      patients (13 males, 56 +/- 16 years) underwent both 1.5 T CMR and TTE. On TTE,
      PLS (absolute values) for each LVM segment from 17 AHA-defined lesions was
      calculated. Of 289 LVM lesions, the numbers in each group, 1-4, were 156, 53, 39,
      and 41, respectively. PLS for LVM segments in group 1 (13.6 +/- 6.4%) were
      significantly greater than those in group 2 (8.5 +/-  4.9%, P < 0.001), group 3
      (10.4 +/- 5.0%, P = 0.006), and group 4 (7.1 +/- 4.4%, P < 0.001). PLS for LVM
      segments in group 3 was significantly greater than those in group 4 (P = 0.016).
      However, significant differences in PLS in LVM between groups 2 and 3, and
      between 2 and 4 were not observed. Using regional PLS, we demonstrate successful
      differentiation of LVM in HCM patients for group 1 (LVM with zero fibrosis or
      hypertrophy) from LVM belonging to groups 2-4 and we also demonstrate successful
      differentiation of LVM with fibrosis present but without hypertrophy from LVM
      with both fibrosis and hypertrophy. However, it is not possible to differentiate
      between LVM with no fibrosis but hypertrophy evident and those with fibrosis
      present but without hypertrophy and also between LVM with no fibrosis but
      hypertrophy evident and those with both fibrosis and hypertrophy. Our findings
      have significant implications for the management of HCM patients.

PMID- 29569033
TI  - Decreased blood glucose at admission has a prognostic impact in patients with
      severely decompensated acute heart failure complicated with diabetes mellitus.
AB  - The prognostic impact of a decreased blood glucose level in acute heart failure
      (AHF) has not been sufficiently clarified. The data from 1234 AHF patients were
      examined in the present study. The blood glucose (BG) levels were evaluated at
      admission. The patients were divided into groups based on the following: with or
      without diabetes mellitus (DM), and BG level >= 200 mg/dl (elevated BG) or < 200
      mg/dl (decreased BG). The elevated and decreased BG patients were further divided
      into another three groups: 200 mg/ml <= BG < 300 mg/dl (mild-elevated), 300 mg/ml
      <= BG < 400 mg/dl (moderate-elevated) and BG >= 400 mg/ml (severe-elevated); and
      150 mg/ml <= BG < 200 mg/dl (mild-decreased), 100 mg/ml <= BG < 150 mg/dl
      (moderate-decreased) and BG < 100 mg/ml (severe-decreased), respectively. The DM
      patients had a significantly poorer mortality than the non-DM patients. The
      prognosis was different between patients with elevated or decreased BG. In DM
      patients with elevated BG, the severe-elevated patients had a significantly
      poorer prognosis than moderate- and mild-elevated patients. In the DM patients
      with decreased BG, the severe-decreased patients had a significantly poorer
      prognosis than those moderate- and mild-decreased patients. The multivariate Cox
      regression model showed that a severe-decreased [hazard ratio (HR) 3.245, 95%
      confidence interval (CI) 1.271-8.282] and severe-elevated (HR 2.300, 95% CI 1.143
      4.628) status were independent predictors of 365-day mortality in AHF patients
      with DM. The mortality was high among AHF patients with DM. Furthermore, both
      severe hyperglycemia and hypoglycemia were independent predictors of the
      mortality in patients with AHF complicated with DM.

PMID- 29569035
TI  - [Radiological imaging of acute infectious and non-infectious enterocolitis].
AB  - BACKGROUND: Computed tomography (CT) is often used as the initial diagnostic test
      in patients with inflammatory and infectious types of enterocolitis. The
      differential diagnosis is broad, including infectious, non-infectious and
      vascular causes, which have substantially different management strategies.
      Although a definitive diagnosis often relies on endoscopic biopsy results, stool
      culture results or other clinical features, radiologists often help to guide the
      diagnosis. OBJECTIVES: This article reviews the CT appearance of different
      infectious and inflammatory forms of enterocolitis. General and specific
      intramural and extramural CT findings in the small bowel and colon are discussed.
      Added focus is placed on distribution patterns and medication side effects that
      can act as important diagnostic clues. RESULTS: Infectious enterocolitis is due
      to bowel inflammation caused by bacteria, viruses, or parasites, which show a
      preferential localization. Pancolitis can be seen with Clostridium difficile with
      the relatively specific CT finding of the "giraffe coat" sign. Inflammatory
      enterocolitis can be primary (inflammatory bowel disease, vasculitis) or
      secondary (radiation therapy, graft versus host disease etc.). Ischemic colitis
      and enteritis can result from arterial compromise, low flow states that globally
      reduce perfusion or venous insufficiency. The CT appearance varies depending on
      the cause, the time of onset and grade of reperfusion. CONCLUSION: Knowledge of
      characteristic mural and extramural CT of MRI findings, geographic distributions
      and therapy effects help to guide the differential diagnostics in inflammatory
      and infectious types of enterocolitis.

PMID- 29569034
TI  - Comparable prognostic impact of BNP levels among HFpEF, Borderline HFpEF and
      HFrEF: a report from the CHART-2 Study.
AB  - We aimed to compare the usefulness of plasma levels of B-type natriuretic peptide
      (BNP) for long-term risk stratification among patients with heart failure (HF)
      with preserved left ventricular ejection fraction (LVEF) (HFpEF), borderline
      HFpEF, and HF with reduced LVEF (HFrEF) in the same HF cohort. In the CHART-2
      Study (N = 10,219), we categorized 4301 consecutive Stage C/D HF patients (mean
      age 68.7 years, female 32.4%) into 3 groups: HFpEF (LVEF >= 50%, N = 2893),
      borderline HFpEF (LVEF 40-50%, N = 666), and HFrEF (LVEF <= 40%, N = 742). During
      the median 6.3-year follow-up, all-cause deaths occurred in 887 HFpEF, 330
      borderline HFpEF, and 330 HFrEF patients. Although median BNP levels increased
      from HFpEF, borderline HFpEF to HFrEF (85.3, 126 and 208 pg/ml, respectively, P <
      0.001), the relationship between log2 BNP levels and the mortality risk was
      comparable among the 3 groups. As compared with patients with BNP < 30 pg/ml,
      those with 30-99, 100-299 and >= 300 pg/ml had comparably increasing mortality
      risk among the 3 groups (hazard ratio 2.5, 4.7 and 7.8 in HFpEF, 2.1, 4.2 and 7.0
      in borderline HFpEF, and 3.0, 4.7 and 9.5 in HFrEF, respectively, all P < 0.001).
      BNP levels have comparable prognostic impact among HFpEF, borderline HFpEF, and
      HFrEF patients.

PMID- 29569036
TI  - Influence of CT-based depth correction of renal scintigraphy in evaluation of
      living kidney donors on side selection and postoperative renal function: is it
      necessary to know the relative renal function?
AB  - PURPOSE: To analyse the influence of CT-based depth correction in the assessment
      of split renal function in potential living kidney donors. METHODS: In 116
      consecutive living kidney donors preoperative split renal function was assessed
      using the CT-based depth correction. Influence on donor side selection and
      postoperative renal function of the living kidney donors were analyzed. Linear
      regression analysis was performed to identify predictors of postoperative renal
      function. RESULTS: A left versus right kidney depth variation of more than 1 cm
      was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than
      5% in relative renal function after depth correction. Kidney depth variation and
      changes in relative renal function after depth correction would have had
      influence on side selection in 30 of 114 living kidney donors. CT depth
      correction did not improve the predictability of postoperative renal function of
      the living kidney donor. In general, it was not possible to predict the
      postoperative renal function from preoperative total and relative renal function.
      In multivariate linear regression analysis, age and BMI were identified as most
      important predictors for postoperative renal function of the living kidney
      donors. CONCLUSIONS: Our results clearly indicate that concerning the
      postoperative renal function of living kidney donors, the relative renal function
      of the donated kidney seems to be less important than other factors. A multimodal
      assessment with consideration of all available results including kidney size,
      location of the kidney and split renal function remains necessary.

PMID- 29569037
TI  - Monoamine oxidase-B inhibitors in the treatment of Parkinson's disease: clinical
      pharmacological aspects.
AB  - This invited narrative review emphasizes the role of MAO-B inhibition in the drug
      portfolio for dopamine substitution in patients with Parkinson's disease.
      Neuronal and glial MAO-B inhibition contributes to more stable levels of dopamine
      and other biogenic amines in the synaptic cleft. Accordingly, symptomatic effects
      of MAO-B inhibition for a limited amelioration of impaired motor behaviour and
      wearing-off phenomena in patients with Parkinson's disease are well proven, even
      when MAO-B inhibitors are only applied together with dopamine agonists. Delay of
      disease progression by MAO-B inhibition is under debate despite positive
      experimental findings. This discussion does not consider, that levodopa,
      respectively, dopamine agonists, are substrates, respectively, inhibitors of the
      ABCB1 (P-gp, MDR1, and CD243) transporter system. It supports toxin efflux over
      the blood-brain barrier. ABCB1 transporters have a limited capacity. MAO-B
      inhibitors do not weaken it. Treatment with MAO-B inhibitors is advantageous as
      it enables sparing of dopamine agonist and levodopa dosing.

PMID- 29569039
TI  - RE: Pathobiology of myomatosis uteri: the underlying knowledge to support our
      clinical practice.

PMID- 29569041
TI  - Non-Invasive Multimodality Imaging Directly Shows TRPM4 Inhibition Ameliorates
      Stroke Reperfusion Injury.
AB  - The transient receptor potential melastatin 4 (TRPM4) channel has been suggested
      to play a key role in the treatment of ischemic stroke. However, in vivo
      evaluation of TRPM4 channel, in particular by direct channel suppression, is
      lacking. In this study, we used multimodal imaging to assess edema formation and
      quantify the amount of metabolically functional brain salvaged after a rat model
      of stroke reperfusion. TRPM4 upregulation in endothelium emerges as early as 2 h
      post-stroke induction. Expression of TRPM4 channel was suppressed directly in
      vivo by treatment with siRNA; scrambled siRNA was used as a control. T2-weighted
      MRI suggests that TRPM4 inhibition successfully reduces edema by 30% and
      concomitantly salvages functionally active brain, measured by 18F-FDG-PET. These
      in vivo imaging results correlate well with post-mortem 2,3,5
      triphenyltetrazolium chloride (TTC) staining which exhibits a 34.9% reduction in
      infarct volume after siRNA treatment. Furthermore, in a permanent stroke model,
      large areas of brain tissue displayed both edema and significant reductions in
      metabolic activity which was not shown in transient models with or without TRPM4
      inhibition, indicating that tissue salvaged by TRPM4 inhibition during stroke
      reperfusion may survive. Evans Blue extravasation and hemoglobin quantification
      in the ipsilateral hemisphere were greatly reduced, suggesting that TRPM4
      inhibition can improve BBB integrity after ischemic stroke reperfusion. Our
      results support the use of TRPM4 blocker for early stroke reperfusion.

PMID- 29569040
TI  - Recurrent Hypoglycemia Exacerbates Cerebral Ischemic Damage in Diabetic Rats via
      Enhanced Post-Ischemic Mitochondrial Dysfunction.
AB  - Diabetes significantly increases the risk of stroke and post-stroke mortality.
      Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose
      lowering therapies. Earlier, we showed that RH in a rat model of insulin
      dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial
      function has been implicated as a central player in the development of cerebral
      ischemic damage. Hypoglycemia is also known to affect mitochondrial functioning.
      The present study tested the hypothesis that prior exposure of insulin-treated
      diabetic (ITD) rats to RH exacerbates brain damage via enhanced post-ischemic
      mitochondrial dysfunction. In a rat model of streptozotocin-induced diabetes, we
      evaluated post-ischemic mitochondrial function in RH-exposed ITD rats. Rats were
      exposed to five episodes of moderate hypoglycemia prior to the induction of
      cerebral ischemia. We also evaluated the impact of RH, both alone and in
      combination with cerebral ischemia, on cognitive function using the Barnes
      circular platform maze test. We observed that RH exposure to ITD rats leads to
      increased cerebral ischemic damage and decreased mitochondrial complex I
      activity. Exposure of ITD rats to RH impaired spatial learning and memory. Our
      results demonstrate that RH exposure to ITD rats potentially increases post
      ischemic damage via enhanced post-ischemic mitochondrial dysfunction.

PMID- 29569042
TI  - "Nobody came to help": interviews with women convicted of filicide in Malaysia.
AB  - Although filicide is of serious concern, it is poorly understood in Malaysia. Our
      interviews with health and policy professionals revealed that they attribute
      responsibility for filicide to women's failure to comply with social norms and
      religious teachings. This research sought to understand the meaning of and
      background to filicide from the perspectives of women who have been convicted of
      filicide in Malaysia. In-depth interviews were conducted in person with all
      eligible and consenting women convicted of filicide and incarcerated in prisons
      or forensic psychiatric institutions. Women's accounts were translated into
      English and analysed using interpretative phenomenological analysis and
      interpreted using narrative theory. Interviews with nine women convicted of
      filicide yielded evidence that others were implicated in the crime but punished
      less severely, if at all, and that the women had experienced lifelong gender
      based violence and marginalisation with minimal access to health and social care.
      These findings illuminate an inadequately understood phenomenon in Malaysia and
      reveal why existing strategies to reduce filicide, which reflect key
      stakeholders' views, have had little impact. They reveal the pervasive harm of
      violence against women and children and its link to filicide.

PMID- 29569043
TI  - Paliperidone and pregnancy-an evaluation of the German Embryotox database.
AB  - Schizophrenic or schizoaffective disorders often occur in early adulthood and
      thus affect women of childbearing age. For paliperidone information about
      reproductive safety is wanting. Therefore, we evaluated data from the German
      Embryotox pharmacovigilance institute regarding paliperidone therapy during
      pregnancy. The German Embryotox pharmacovigilance institute offers risk
      assessment on drug use in pregnancy and documents the outcome of more than 3500
      drug-exposed pregnancies per year. In our study, we analyze the outcome of all
      pregnancies with paliperidone exposure, which have been assessed by our institute
      between January 2007 and June 2016. Of the 17 prospectively assessed pregnancies,
      14 resulted in 15 live-born children (including one pair of twins). None of the
      infants presented with major congenital malformations. There were two spontaneous
      abortions at gestational weeks 6 and 11, respectively, and one elective
      termination due to personal reasons. Sixty-five percent of the pregnant women
      smoked cigarettes throughout pregnancy, 17% consumed alcohol. Five children were
      born prematurely (< 37 gestational weeks) and four were small for gestational
      age, each group including the twins. The results of our study suggest that
      paliperidone may be administered during pregnancy. The increased rate of
      prematurity and small for gestational age children can at least partially be
      explained by other risk factors. Psychiatric and obstetric close monitoring as
      well as additional medical and social support are recommended to ensure a healthy
      pregnancy course in patients with a severe mental illness.

PMID- 29569044
TI  - Impact of a training program on adherence to recommendations for care of venous
      lines in internal medicine departments in Spain.
AB  - A high percentage of venous lines (VLs) are placed in non-ICU patients,
      particularly those treated in the internal medicine department (IMD). We assessed
      adherence to VL care after a training program aimed at nurses and clinicians
      attending patients admitted to Spanish IMDs. We performed a multicenter
      prospective observational point prevalence study in 14 Spanish IMDs in 2013 and
      2016. We included all adult patients (> 18 years) admitted to IMDs on the study
      day and reviewed nursing records for patients with VL in place before and after a
      1-year training program during 2015. Answers from an interview with head nurses
      of the IMDs regarding commonly used practices in the daily management of VLs were
      also compared. A total of 638 and 693 patients were seen during each period,
      respectively, and 530 and 598 patients had >= 1 VL implanted (83.1 vs. 86.3%).
      Catheters were considered unnecessary in 12.8 and 15.0% of cases (p = 0.28).
      Daily recording of the need for catheter use increased from 43.8 to 71.8% (p <
      0.001). Furthermore, daily monitoring of the insertion site remained very
      frequent (94.4 vs. 92.2%; p = 0.16). The date of insertion was recorded in 86.3
      and 85.5% of cases (p = 0.73), and no combination of closed connectors with open
      caps increased from 74.8 to 90.3% (p < 0.001). Overall, head nurses' knowledge
      improved in 4 out of 14 recommendations assessed (28.6%). A simple and easy
      program for training on management of VLs in Spanish IMDs was associated with
      improved quality of care.

PMID- 29569047
TI  - Alterations in resting-state gamma activity in patients with schizophrenia: a
      high-density EEG study.
AB  - Alterations of EEG gamma activity in schizophrenia have been reported during
      sensory and cognitive tasks, but it remains unclear whether changes are present
      in resting state. Our aim was to examine whether changes occur in resting state,
      and to delineate those brain regions where gamma activity is altered.
      Furthermore, we wanted to identify the associations between changes in gamma
      activity and psychopathological characteristics. We studied gamma activity (30-48
      Hz) in 60 patients with schizophrenia and 76 healthy controls. EEGs were acquired
      in resting state with closed eyes using a high-density, 256-channel EEG-system.
      The two groups were compared in absolute power measures in the gamma frequency
      range. Compared to controls, in patients with schizophrenia the absolute power
      was significantly elevated (false discovery rate corrected p < 0.05). The
      alterations clustered into fronto-central and posterior brain regions, and were
      positively associated with the severity of psychopathology, measured by the
      PANSS. Changes in gamma activity can lead to disturbed coordination of large
      scale brain networks. Thus, the increased gamma activity in certain brain regions
      that we found may result in disturbances in temporal coordination of task
      free/resting-state networks in schizophrenia. Positive association of increased
      gamma power with psychopathology suggests that altered gamma activity provides a
      contribution to symptom presentation.

PMID- 29569046
TI  - In vitro antibacterial effects of statins against bacterial pathogens causing
      skin infections.
AB  - With financial considerations impeding research and development of new
      antibiotics, drug repurposing (finding new indications for old drugs) emerges as
      a feasible alternative. Statins are extensively prescribed around the world to
      lower cholesterol, but they also possess inherent antimicrobial properties. This
      study identifies statins with the greatest potential to be repurposed as topical
      antibiotics and postulates a mechanism of action for statins' antibacterial
      activity. Using broth microdilution, the direct antibacterial effects of all
      seven parent statins currently registered for human use and three selected statin
      metabolites were tested against bacterial skin pathogens Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin
      and pitavastatin lactone exerted the greatest antibacterial effects (minimum
      inhibitory concentrations of 64 and 128 MUg/mL, respectively) against S. aureus.
      None of the statins tested were effective against E. coli, P. aeruginosa, or S.
      marcescens, but simvastatin hydroxy acid acid might be active against S. aureus,
      E. coli, and S. marcescens at drug concentrations > 256 MUg/mL. It was found that
      S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin;
      thus, treatment failure at high drug concentrations is theoretically probable.
      Through structure-activity relationship analysis, we postulate that statins'
      antibacterial action may involve disrupting the teichoic acid structures or
      decreasing the number of alanine residues present on Gram-positive bacterial cell
      surfaces, which could reduce biofilm formation, diminish bacterial adhesion to
      environmental surfaces, or impede S. aureus cell division.

PMID- 29569045
TI  - Recent advances in rapid pathogen detection method based on biosensors.
AB  - As strain variation and drug resistance become more pervasive, the prevention and
      control of infection have been a serious problem in recent years. The detection
      of pathogen is one of the most important parts of the process of diagnosis.
      Having a series of advantages, such as rapid response, high sensitivity, ease of
      use, and low cost, biosensors have received much attention and been studied
      deeply. Moreover, relying on its characteristics of small size, real time, and
      multiple analyses, biosensors have developed rapidly and used widely and are
      expected to be applied for microbiological detection in order to meet higher
      accuracy required by clinical diagnosis. The main goal of this contribution is
      not to simply collect and list all papers related to pathogen detection based on
      biosensors published recently, but to discuss critically the development and
      application of many kinds of biosensors such as electrochemical (amperometric,
      impedimetric, potentiometric, and conductometric), optical (fluorescent, fibre
      optic and surface plasmon resonance), and piezoelectric (quartz crystal
      microbalances and atomic force microscopy) biosensors in pathogen detection as
      well as the comparisons with the existing clinical detection methods (traditional
      culture, enzyme-linked immunosorbent assay, polymerase chain reaction, and mass
      spectrometry).

PMID- 29569048
TI  - A Metagenome-Based Investigation of Gene Relationships for Non-Substrate
      Associated Microbial Phosphorus Cycling in the Water Column of Streams and
      Rivers.
AB  - Phosphorus (P) is a nutrient of primary importance in all living systems, and it
      is especially important in streams and rivers which are sensitive to
      anthropogenic P inputs and eutrophication. Microbes are accepted as the primary
      mineralizers and solubilizers of P improving bioavailability for organisms at all
      trophic levels. Here, we use a genomics approach with metagenome sequencing of 24
      temperate streams and rivers representing a total P (TP) gradient to identify
      relationships between functional genes, functional gene groupings, P, and
      organisms within the P biogeochemical cycle. Combining information from network
      analyses, functional groupings, and system P levels, we have constructed a System
      Relational Overview of Gene Groupings (SROGG) which is a cohesive system level
      representation of P cycle gene and nutrient relationships. Using SROGG analysis
      in concert with other statistical approaches, we found that the compositional
      makeup of P cycle genes is strongly correlated to environmental P whereas
      absolute abundance of P genes shows no significant correlation to environmental
      P. We also found orthophosphate (PO43-) to be the dominant factor correlating
      with system P cycle gene composition with little evidence of a strong organic
      phosphorous correlation present even in more oligotrophic streams.

PMID- 29569049
TI  - CT for evaluation of acute pericardial emergencies in the ED.
AB  - Acute pericardial emergencies may present with acute chest pain. Although
      complete diagnosis and physiological effects of acute pericardial disease may
      require a combination of different imaging, CT plays a critical role in
      identifying the cause of chest pain in the ED. Many of these pericardial diseases
      can be fatal unless emergent treatment is obtained. The presentation can often be
      non-specific and symptoms can be overlapping with other diseases originating in
      the thorax or abdomen. Optimizing the CT scan is imperative when acute
      pericardial disease is suspected from clinical examination or preliminary
      imaging. The interpreting radiologist needs to be aware of the different entities
      which represent acute pericardial emergencies requiring urgent therapeutic
      intervention. Time is the essence, the clock is ticking, and every minute counts!

PMID- 29569050
TI  - Anaerobic digestion performance of sweet potato vine and animal manure under wet,
      semi-dry, and dry conditions.
AB  - Sweet potato vine (SPV) is an abundant agricultural waste, which is easy to
      obtain at low cost and has the potential to produce clean energy via anaerobic
      digestion (AD). The main objectives of this study were to reveal methane
      production and process stability of SPV and the mixtures with animal manure under
      various total solid conditions, to verify synergetic effect in co-digestion of
      SPV and manure in AD systems, and to determine the kinetics characteristics
      during the full AD process. The results showed that SPV was desirable feedstock
      for AD with 200.22 mL/g VSadded of methane yield in wet anaerobic digestion and
      12.20 Lmethane/Lworking volume in dry anaerobic digestion (D-AD). Synergistic
      effects were found in semi-dry anaerobic digestion and D-AD with each two mixing
      feedstock. In contrast with SPV mono-digestion, co-digestion with manure
      increased methane yield within the range of 14.34-49.11% in different AD
      digesters. The values of final volatile fatty acids to total alkalinity (TA) were
      below 0.4 and the values of final pH were within the range of 7.4-8.2 in all the
      reactors, which supported a positive relationship between carbohydrate hydrolysis
      and methanogenesis during AD process. The mathematical modified first order model
      was applied to estimate substrate biodegradability and methane production
      potential well with conversion constant ranged from 0.0003 to 0.0953 1/day, which
      indicated that co-digestion increased hydrolysis efficiency and metabolic
      activity. This work provides useful information to improve the utilization and
      stability of digestion using SPV and livestock or poultry manure as substrates.

PMID- 29569051
TI  - Induction and relocalization of telomeric repeat-containing RNAs during diauxic
      shift in budding yeast.
AB  - Telomeres are maintained in a heterochromatic state that represses transcription
      of subtelomeric genes, a phenomenon known as telomere position effect.
      Nevertheless, telomeric DNA is actively transcribed, leading to the synthesis of
      telomeric repeat-containing noncoding RNA or TERRA. This nuclear noncoding RNA
      has been proposed to play important roles at telomeres, regulating their
      silencing, capping, repair and elongation by telomerase. In the budding yeast
      Saccharomyces cerevisiae, TERRA accumulation is repressed by telomeric silencing
      and the Rat1 exonuclease. On the other hand, telomere shortening promotes
      expression of TERRA. So far, little is known about the biological processes that
      induce TERRA expression in yeast. Understanding the dynamics of TERRA expression
      and localization is essential to define its function in telomere biology. Here,
      we aim to study the dynamics of TERRA expression during yeast cell growth. Using
      live-cell imaging, RNA-FISH and quantitative RT-PCR, we show that TERRA
      expression is induced as yeast cells undergo diauxic shift, a lag phase during
      which yeast cells switch their metabolism from anaerobic fermentation to
      oxidative respiration. This induction is transient as TERRA levels decrease
      during post-diauxic shift. The increased expression of TERRA is not due to the
      shortening of telomeres or increased stability of this transcript. Surprisingly,
      this induction is coincident with a cytoplasmic accumulation of TERRA molecules.
      Our results suggest that TERRA transcripts may play extranuclear functions with
      important implications in telomere biology and add a novel layer of complexity in
      the interplay between telomere biology, metabolism and stress response.

PMID- 29569052
TI  - Managing Couple Conflict During Prenatal Counseling Sessions: An Investigation of
      Genetic Counselor Experiences and Perceptions.
AB  - Research shows couple conflict occurring during prenatal genetic counseling
      sessions may be challenging for some genetic counselors. Yet, no study has
      explored couple conflict in depth. The current study investigated genetic
      counselors' experiences and perceptions of the nature and context of couple
      conflict in prenatal sessions and counselor conflict management strategies.
      Sixteen prenatal genetic counselors recruited through the National Society of
      Genetic Counselors participated in semi-structured phone interviews asking about
      how they recognize couple conflict; topics that trigger conflict and when it
      occurs; individual, cultural, and situational factors associated with conflict;
      conflict management strategies; and specific examples from their practice.
      Inductive and cross-case comparison methods revealed a number of themes. Genetic
      counselors recognize couple conflict through non-verbal and verbal cues, and
      conflict can occur at any time, particularly during decision-making about testing
      and test results and during results review of an affected pregnancy. Factors
      associated with conflict include cultural customs, age, emotional state,
      religious beliefs, and being forced to attend counseling. Participants identified
      23 conflict management strategies classified into five themes: facilitate
      decision-making, encourage couple expression, act within one's scope of practice,
      provide psychosocial support, and support the identified patient. Counselors
      emphasized that their strategies are couple dependent. Patients may benefit from
      genetic counselors assessing couple conflict and intervening when it impedes
      genetic counseling goals. Clinical examples from this study may contribute to
      informing genetic counselor practice, program curricula, and continuing education
      workshops.

PMID- 29569053
TI  - Response to Commercial Genetic Testing and the Future of the Genetic Counseling
      Profession.

PMID- 29569054
TI  - Perfusion dynamics assessment with Power Doppler ultrasound in skeletal muscle
      during maximal and submaximal cycling exercise.
AB  - PURPOSE: Assessment of limitations in the perfusion dynamics of skeletal muscle
      may provide insight in the pathophysiology of exercise intolerance in, e.g.,
      heart failure patients. Power doppler ultrasound (PDUS) has been recognized as a
      sensitive tool for the detection of muscle blood flow. In this volunteer study (N
      = 30), a method is demonstrated for perfusion measurements in the vastus
      lateralis muscle, with PDUS, during standardized cycling exercise protocols, and
      the test-retest reliability has been investigated. METHODS: Fixation of the
      ultrasound probe on the upper leg allowed for continuous PDUS measurements.
      Cycling exercise protocols included a submaximal and an incremental exercise to
      maximal power. The relative perfused area (RPA) was determined as a measure of
      perfusion. Absolute and relative reliability of RPA amplitude and kinetic
      parameters during exercise (onset, slope, maximum value) and recovery (overshoot,
      decay time constants) were investigated. RESULTS: A RPA increase during exercise
      followed by a signal recovery was measured in all volunteers. Amplitudes and
      kinetic parameters during exercise and recovery showed poor to good relative
      reliability (ICC ranging from 0.2-0.8), and poor to moderate absolute reliability
      (coefficient of variation (CV) range 18-60%). CONCLUSIONS: A method has been
      demonstrated which allows for continuous (Power Doppler) ultrasonography and
      assessment of perfusion dynamics in skeletal muscle during exercise. The
      reliability of the RPA amplitudes and kinetics ranges from poor to good, while
      the reliability of the RPA increase in submaximal cycling (ICC = 0.8, CV = 18%)
      is promising for non-invasive clinical assessment of the muscle perfusion
      response to daily exercise.

PMID- 29569056
TI  - The role of long-range coupling in crayfish swimmeret phase-locking.
AB  - During forward swimming, crayfish and other long-tailed crustaceans rhythmically
      move four pairs of limbs called swimmerets to propel themselves through the
      water. This behavior is characterized by a particular stroke pattern in which the
      most posterior limb pair leads the rhythmic cycle and adjacent swimmerets paddle
      sequentially with a delay of roughly 25% of the period. The neural circuit
      underlying limb coordination consists of a chain of local modules, each of which
      controls a pair of limbs. All modules are directly coupled to one another, but
      the inter-module coupling strengths decrease with the distance of the connection.
      Prior modeling studies of the swimmeret neural circuit have included only the
      dominant nearest-neighbor coupling. Here, we investigate the potential modulatory
      role of long-range connections between modules. Numerical simulations and
      analytical arguments show that these connections cause decreases in the phase
      differences between neighboring modules. Combined with previous results from a
      computational fluid dynamics model, we posit that this phenomenon might ensure
      that the resultant limb coordination lies within a range where propulsion is
      optimal. To further assess the effects of long-range coupling, we modify the
      model to reflect an experimental preparation where synaptic transmission from a
      middle module is blocked, and we generate predictions for the phase-locking
      properties in this system.

PMID- 29569055
TI  - Collision activity during training increases total energy expenditure measured
      via doubly labelled water.
AB  - PURPOSE: Collision sports are characterised by frequent high-intensity collisions
      that induce substantial muscle damage, potentially increasing the energetic cost
      of recovery. Therefore, this study investigated the energetic cost of collision
      based activity for the first time across any sport. METHODS: Using a randomised
      crossover design, six professional young male rugby league players completed two
      different 5-day pre-season training microcycles. Players completed either a
      collision (COLL; 20 competitive one-on-one collisions) or non-collision (nCOLL;
      matched for kinematic demands, excluding collisions) training session on the
      first day of each microcycle, exactly 7 days apart. All remaining training
      sessions were matched and did not involve any collision-based activity. Total
      energy expenditure was measured using doubly labelled water, the literature gold
      standard. RESULTS: Collisions resulted in a very likely higher (4.96 +/- 0.97 MJ;
      ES = 0.30 +/- 0.07; p = 0.0021) total energy expenditure across the 5-day COLL
      training microcycle (95.07 +/- 16.66 MJ) compared with the nCOLL training
      microcycle (90.34 +/- 16.97 MJ). The COLL training session also resulted in a
      very likely higher (200 +/- 102 AU; ES = 1.43 +/- 0.74; p = 0.007) session rating
      of perceived exertion and a very likely greater (- 14.6 +/- 3.3%; ES = - 1.60 +/-
      0.51; p = 0.002) decrease in wellbeing 24 h later. CONCLUSIONS: A single
      collision training session considerably increased total energy expenditure. This
      may explain the large energy expenditures of collision-sport athletes, which
      appear to exceed kinematic training and match demands. These findings suggest
      fuelling professional collision-sport athletes appropriately for the "muscle
      damage caused" alongside the kinematic "work required".

PMID- 29569057
TI  - [Mechanical pupillary dilatation using rings in small pupils during cataract
      surgery : Video article].
AB  - OBJECTIVE: The purpose of mechanical pupillary dilatation in small pupils is a
      sufficient visualization of the lens to be able to perform capsulorhexis,
      phacoemulsification and intraocular lens implantation. INDICATIONS: The
      indications for mechanical dilatation are fulfilled in patients where a
      sufficient pharmacological preoperative pupil dilatation is not possible.
      SURGICAL TECHNIQUE: During routine cataract surgery specific foldable rings can
      be employed to dilate the pupil with the appropriate injector under viscoelastic
      substances. These rings are carefully placed at the pupillary margin until
      circular pupillary dilatation up to 6-7 mm is achieved. After intraocular lens
      implantation and before removing the viscoelastic substance the rings are slowly
      folded into the injector and then removed. The surgical technique is demonstrated
      in detail with the help of a video of the operation, which is available online.
      RESULTS: Mechanical pupillary dilatation was possible in all patients studied (n
      = 14), which allowed uncomplicated phacoemulsification and intraocular lens
      implantation. For both ring systems studied the mean pupillary dilatation was 6.6
      mm. At the end of surgery, the pupillary diameter was 4.89 mm using a Malyugin
      ring (MST, Redmond, Washington, USA) and 4.93 mm with an I-ring (Visitec,
      Waltham, MA, USA; P > 0.05). Small lesions at the pupillary margin or pigment
      dispersion during implantation or explantation depended mostly on the individual
      patient situation and not on the ring used. CONCLUSION: Mechanical pupillary
      dilatation with rings allows sufficient dilatation to perform cataract surgery.
      Both the Malyugin ring and the I-ring achieved smooth and atraumatic pupillary
      dilatation.

PMID- 29569059
TI  - Author Correction: Opium Consumption and the Incidence of Cancer: Does Opium
      Account as an Emerging Risk Factor for Gastrointestinal Cancer?
AB  - The original version of this article unfortunately contained a mistake in the
      author group section. The correct name of the fourth author is "Reza
      Shirkoohi."The original article has been corrected.

PMID- 29569058
TI  - Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting
      oxidative stress and inflammation.
AB  - Plumbagin, a vitamin K3 analogue is the major active constituent in several
      plants including root of Plumbago indica Linn. This compound has been shown to
      exhibit a wide spectrum of pharmacological activities. The present investigation
      was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria
      pathogenesis due to involvement of oxidative stress and inflammatory response in
      Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by
      intra-peritoneal injection of P. berghei infected red blood cells into the Swiss
      albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day
      following Peter's 4 day suppression test. Oral administration of PL showed
      significant reduction of parasitaemia and increase in mean survival time. PL
      treatment is also attributed to significant increase in the blood glucose and
      haemoglobin level when compared with vehicle-treated infected mice. Significant
      inhibition in level of oxidative stress and pro-inflammation related markers were
      observed in PL treated group. The trend of inhibition in oxidative stress markers
      level after oral treatment of PL was MPO > LPO > ROS in organ injury in P.
      berghei infected mice. This study showed that plumbagin is able to ameliorate
      malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism
      apart from its effect on reducing parasitaemia and increasing mean survival time
      of malaria-induced mice.

PMID- 29569061
TI  - Expression of Genes Associated with Nickel Resistance in Red Oak (Quercus rubra)
      Populations from a Metal Contaminated Region.
AB  - Although many studies have reported mechanisms of resistance to metals in
      herbaceous species, there is very little information on metal coping strategy in
      hardwood species such as Quercus rubra. The main objective of this study was to
      determine the expression of genes associated with nickel resistance in red oak
      (Q. rubra) populations from metal contaminated and uncontaminated sites in the
      Northern Ontario. Six genes associated with nickel resistances in model and non
      model plants were targeted. Differential expressions of these genes were observed
      in Q. rubra from all the sites, but association between metal contamination and
      gene expression was not established. This suggests that the bioavailable amounts
      of metals found in metal contaminated soils in mining sites in northern Ontario
      and likely in many mining regions around the world cannot trigger a genetic
      response in higher plant species.

PMID- 29569060
TI  - Predictors of portal and splenic vein thrombosis after laparoscopic splenectomy:
      a retrospective analysis of a single-center experience.
AB  - PURPOSE: Laparoscopic splenectomy (LS) has become the standard operative approach
      for splenectomy. Portal or splenic vein thrombosis (PSVT) is a serious and common
      complication after LS, and lethal complications of PSVT can occur when the portal
      vein is completely occluded by portal vein thrombosis (PVT). We aimed to clarify
      the predictors of PSVT after LS and to determine which of them were also
      predictors of PVT. METHODS: A total of 56 consecutive patients who underwent
      elective LS were enrolled in this study. The patients were divided into two
      groups based on the presence or absence of PSVT after LS. In addition, patients
      with PSVT were divided into two groups: a PVT group and a non-PVT group. The
      preoperative and intraoperative clinical data were compared among the groups.
      RESULTS: Thirty (53.6%) patients developed PSVT. The splenic vein diameter was
      the most useful predictor for the development of PSVT, and 10 mm was an accurate
      splenic vein diameter cut-off value for use as a predictive factor for PSVT. In
      addition, the splenic vein diameter was the most useful predictor of the
      development of PVT from splenic vein thrombosis (SVT), and 14 mm was found to be
      an accurate cut-off value. CONCLUSION: PSVT is a common postoperative
      complication that is identified on enhanced computed tomography. The splenic vein
      diameter is not only a predictor of PSVT but also of the development of PVT from
      SVT.

PMID- 29569062
TI  - Partial mRNA Sequences of the Biomarkers CYP1A, GST, CAT, GR, SOD, GPx, VTG and
      p53 in Flatfish Syacium gunteri from Gulf of Mexico.
AB  - The present study reports partial sequences of a group of genes used as exposure
      and effect biomarkers of organic contaminants and/or heavy metals in Syacium
      gunteri. In order to isolate these sequences, cDNA was used to amplify fragments
      between 200 and 800 bp, which were then cloned and sequenced. The sequences
      presented high percentages of identity with genes involved in the metabolism of
      xenobiotic biotransformation (cytochrome P4501A and glutathione S-transferase),
      oxidative stress (catalase, glutathione reductase, glutathione peroxidase and
      superoxide dismutase), reproductive system (vitellogenin) and with the tumor
      suppressor protein p53 reported in the GenBank database. Subsequently, from the
      deduced sequence of amino acids of each fragment, their tridimensional structure
      was predicted, using homologous proteins from the Protein Data Base. This study
      generates an important base of molecular biomarkers for the monitoring of
      environmental health in the Gulf of Mexico.

PMID- 29569063
TI  - [Arthroscopic double-row reconstruction of high-grade subscapularis tendon
      tears].
AB  - OBJECTIVE: Reconstruction of tendon integrity to maintain glenohumeral joint
      centration and hence to restore shoulder functional range of motion and to reduce
      pain. INDICATIONS: Isolated or combined full-thickness subscapularis tendon tears
      (>=upper two-thirds of the tendon) without both substantial soft tissue
      degeneration and cranialization of the humeral head. CONTRAINDICATIONS: Chronic
      tears of the subscapularis tendon with higher grade muscle atrophy, fatty
      infiltration, and static decentration of the humeral head. SURGICAL TECHNIQUE:
      After arthroscopic three-sided subscapularis tendon release, two double-loaded
      suture anchors are placed medially to the humeral footprint. Next to the suture
      passage, the suture limbs are tied and secured laterally with up to two knotless
      anchors creating a transosseous-equivalent repair. POSTOPERATIVE MANAGEMENT: The
      affected arm is placed in a shoulder brace with 20 degrees  of abduction and
      slight internal rotation for 6 weeks postoperatively. Rehabilitation protocol
      including progressive physical therapy from a maximum protection phase to a
      minimum protection phase is required. Overhead activities are permitted after 6
      months. RESULTS: While previous studies have demonstrated superior biomechanical
      properties and clinical results after double-row compared to single-row and
      transosseous fixation techniques, further mid- to long-term clinical
      investigations are needed to confirm these findings.

PMID- 29569064
TI  - Embodiment and Entangled Subjectivity: A Study of Robin Cook's Coma, Priscille
      Sibley's The Promise of Stardust and Alexander Beliaev's Professor Dowell's Head.
AB  - The essay examines Robin Cook's (1977) Coma and Priscille Sibley's (2013) The
      Promise of Stardust that dramatize the reified and disposable status of the brain
      dead patients who are classified as nonpersons. The essay argues that the man
      machine entanglement as depicted in the novels constructs a deterritorialized and
      entangled form of subjectivity that intervenes in the dominant biomedical
      understanding of personhood and agency that we notionally associate with a
      conscious mind. The essay concludes its arguments by discussing Alexander
      Beliaev's (1925) Professor Dowell's Head which depicts human subjectivity as an
      essentially embodied and distributive phenomenon and interrogates the Cartesian
      mind body dualism embedded in the dominant biomedical narratives.

PMID- 29569065
TI  - Deterministic and Probabilistic Record Linkage: an Application to Primary Care
      Data.

PMID- 29569066
TI  - Physicochemical properties associated with the presence of Burkholderia
      pseudomallei in small ruminant farm water supplies in Peninsular Malaysia.
AB  - Burkholderia pseudomallei causes melioidosis, a life-threatening infection in
      both humans and animals. Water is an important reservoir of the bacteria and may
      serve as a source of environmental contamination leading to infection. B.
      pseudomallei has an unusual ability to survive in water for a long period. This
      paper investigates physicochemical properties of water associated with the
      presence of B. pseudomallei in water supply in small ruminant farms in Peninsular
      Malaysia. Physicochemical properties of water samples taken from small ruminant
      farms that included temperature, pH, dissolved oxygen (DO2), optical density
      (OD), and chemical oxygen demand (COD) were measured after which the samples were
      cultured for B. pseudomallei. Multivariable logistic regression model revealed
      that slightly acidic water pH and higher COD level were significantly associated
      with the likelihood of the B. pseudomallei presence in the water.

PMID- 29569067
TI  - Spin- and Valley-Dependent Electronic Structure in Silicene Under Periodic
      Potentials.
AB  - We study the spin- and valley-dependent energy band and transport property of
      silicene under a periodic potential, where both spin and valley degeneracies are
      lifted. It is found that the Dirac point, miniband, band gap, anisotropic
      velocity, and conductance strongly depend on the spin and valley indices. The
      extra Dirac points appear as the voltage potential increases, the critical values
      of which are different for electron with different spins and valleys.
      Interestingly, the velocity is greatly suppressed due to the electric field and
      exchange field, other than the gapless graphene. It is possible to achieve an
      excellent collimation effect for a specific spin near a specific valley. The spin
      and valley-dependent band structure can be used to adjust the transport, and
      perfect transmissions are observed at Dirac points. Therefore, a remarkable spin
      and valley polarization is achieved which can be switched effectively by the
      structural parameters. Importantly, the spin and valley polarizations are greatly
      enhanced by the disorder of the periodic potential.

PMID- 29569068
TI  - Complete genome sequence of a new bipartite begomovirus infecting Boehmeria
      leiophylla in China.
AB  - A bipartite begomovirus was identified from a Boehmeria leiophylla plant sample
      exhibiting yellow mosaic symptoms collected in Nabanhe National Nature Reserve,
      Xishuangbanna, Yunnan, China. Five complete DNA-A and four DNA-B genome sequences
      were obtained by rolling-circle amplification (RCA), cloned, and sequenced. All
      DNA-A sequences were determined to be 2759 nucleotides in size, sharing 99.9%
      100% nucleotide sequence identity with each other. The DNA-B sequences were
      comprised of 2673 nucleotides, sharing 98.6-100% nucleotide sequence identity
      with each other. Genomic organization of the begomovirus was typical of Old World
      bipartite begomoviruses. Sequence analysis revealed 81.84% nucleotide sequence
      identity to tomato leaf curl Hsinchu virus (ToLCHsV) from China for the DNA A
      component and 67.23% identity to the squash leaf curl China virus (SLCCNV) from
      India for the DNA B component. The sequence comparisons suggest that this
      bipartite begomovirus represents a novel species for which we propose the name
      "Ramie yellow mosaic virus".

PMID- 29569069
TI  - Complete genome sequence of a novel virulent phage ST31 infecting Escherichia
      coli H21.
AB  - More and more virulent phages that are fundamental materials for phage therapy
      have been isolated, characterized and categorized on GenBank. Phage ST31
      infecting Escherichia coli H21 was isolated from wastewater and sequenced using
      an Illumina Hiseq system. Opening reading frames were identified using PHASTER
      and predicted using BLASTp analysis. Genomic analyses revealed that this was a
      virulent phage containing a circular double-stranded DNA and that the complete
      genome consisted of 39,693 nucleotides with an average GC content of 49.98 %.
      This study may provide possible alternative materials for phage therapy.

PMID- 29569070
TI  - Detection and genetic characterization of porcine astroviruses in piglets with
      and without diarrhea in Thailand.
AB  - Porcine astrovirus (PAstV) is widely distributed and highly prevalent among pigs,
      nevertheless its clinical significance remains unclear as it can be detected in
      both diarrheic and in healthy pigs. Information about the prevalence, clinical
      significance and molecular characterization of PAstV in Thailand is not
      available. This study investigated the prevalence of PAstV in 488 fecal samples
      collected from piglets with and without diarrhea in 28 pig farms in northern and
      central parts of Thailand using RT-PCR. The overall prevalence of PAstV infection
      was 6.5% (32/488), of which 21/251 (8.4%) were in diarrheic and 11/237 (4.6%)
      were in healthy pigs. Of 32 positive samples, 46.9% were positive for PAstV alone
      whereas 53.1% were co-infected with porcine group A rotavirus (PRVA). A
      phylogenetic analysis of the partial RNA-dependent RNA polymerase/capsid genes
      revealed two lineages of PAstV strains detected in this study. PAstV4 was the
      most dominant genotype (92%), followed by PAstV2 (8%). This study revealed for
      the first time that PAstV4 and PAstV2 were circulating in Thailand with PAstV4 as
      the most dominant genotype in pig herds in northern and central parts of
      Thailand.

PMID- 29569071
TI  - Coloproctology procedure clinic: a novel service developed to reduce suffering of
      patients with bleeding per rectum.
AB  - AIMS: Evaluation of the role and impact of introducing a dedicated coloproctology
      procedure clinic in tertiary referral colorectal unit. METHODS: A retrospective
      analysis of 126 consecutive patients managed in the coloproctology clinic between
      March2015 and September 2016 was carried out. All patients were preselected for
      attendance based on symptom-based protocol. RESULTS: Based on the information
      available in GP referrals, 126 patients with bleeding per rectum with low risk of
      cancer were re-triaged from the general outpatient to dedicated coloproctology
      procedure clinic. Those patients accounted for 14% of waiting list. The average
      waiting time to attend clinic was 27 months from referral to undergoing
      definitive procedure. A proctoscopy or/and rigid sigmoidoscopy was performed in
      patients. Seventy-nine (89.7%) patients were completely managed and discharged
      after attending their first visit. Sixty-seven (76%) patients had 2nd- or 3rd
      degree haemorrhoids and were treated with rubber band ligation (RBL) or phenol
      injection in outpatient setting. Two patients had an anal fissure and were
      managed conservatively with medication. After clinic, follow-up was through
      telephone clinic. This avoids attendance physically in the hospital. Symptoms
      persisted in nine patients and were subsequently scheduled for colonoscopy, three
      had benign polyps. With the introduction of the procedure clinic, the waiting
      time from referral to treatment was reduced from 27 to 6 months (p < 0.05).
      CONCLUSIONS: Establishing a dedicated "Coloproctology procedure clinic" is an
      effective strategy in reducing number of hospital visits per patient and hospital
      waiting list. This innovative clinic reduces utilisation of precious endoscopy
      unit resources. This ultimately will improve endoscopy efficiency.

PMID- 29569073
TI  - Impact of colorectal surgeon case volume on outcomes and applications to quality
      improvement.
AB  - PURPOSE: To evaluate the impact of surgeon case volumes on procedural, financial,
      and clinical outcomes in colorectal surgery and apply findings to improve
      hospital care quality. METHODS: A retrospective review was performed using 2013
      2014 administrative data from a large hospital system in Southeast U.S. region;
      univariate and multivariable regression analyses were used to explore the impact
      of surgeon case volume on outcomes. RESULTS: One thousand one hundred ninety
      patients were included in this 2-year study. When compared with low-volume
      surgeons (LVS) (< 14 cases in 2 years), the high-volume surgeons (HVS) (> 34
      cases) were estimated per case to have shorter cut-to-close time in the operation
      room by 79 min, ([95% CI 58 to 99]), lower total hospitalization cost by $4314,
      ([95% CI $2261 to $6367]), and shorter post-surgery and overall length of stay by
      0.92 days, ([95% CI 0.50 to 1.35]) and 1.27 days ([95% CI 0.56 to 1.98]),
      respectively. The HVS also showed a higher tendency to choose a laparoscopic
      approach over an open approach, with an odds ratio of 3.16 ([95% CI 1.23 to
      8.07]). When compared with medium-volume surgeons (MVS) (14-34 cases), the HVS
      were estimated per case to have shorter cut-to-close time in the operation room
      by 62 min ([95% CI 37 to 87]). Surgeon case volumes had no statistically
      significant impact on outcomes including in-hospital mortality, 30-day
      readmission, blood utilization, and surgical site infection (SSI). CONCLUSIONS:
      Surgeon case volume had positive impacts on procedural, financial, and clinical
      outcomes and this finding may be used to improve hospital's quality of care.

PMID- 29569072
TI  - Posttranslational modifications of CENP-A: marks of distinction.
AB  - Centromeres are specialized chromosome domain that serve as the site for
      kinetochore assembly and microtubule attachment during cell division, to ensure
      proper segregation of chromosomes. In higher eukaryotes, the identity of active
      centromeres is marked by the presence of CENP-A (centromeric protein-A), a
      histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a
      foundation for centromere assembly and function. The posttranslational
      modification (PTM) of histone proteins is a major mechanism regulating the
      function of chromatin. While a few CENP-A site-specific modifications are shared
      with histone H3, the majority are specific to CENP-A-containing nucleosomes,
      indicating that modification of these residues contribute to centromere-specific
      function. CENP-A undergoes posttranslational modifications including
      phosphorylation, acetylation, methylation, and ubiquitylation. Work from many
      laboratories have uncovered the importance of these CENP-A modifications in its
      deposition at centromeres, protein stability, and recruitment of the CCAN
      (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A
      and their biological relevance.

PMID- 29569074
TI  - Acaricidal and repellent effects of Cnidium officinale-derived material against
      Dermanyssus gallinae (Acari: Dermanyssidae).
AB  - The acaricidal activity of a methanolic extract and fractions from the rhizome of
      Cnidium officinale against Dermanyssus gallinae adults was investigated. The C.
      officinale methanolic extract exhibited 100% acaricidal activity after 48 h of
      treatment at a dose of 4000 ppm. The acaricidal constituents of the plant were
      sequentially partitioned with several solvents and then purified using silica gel
      column chromatography and high-performance liquid chromatography. Gas
      chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy
      revealed (Z)-ligustilide as a constituent of C. officinale. Acaricidal activity
      was examined in three experimental tests (spray, fumigation and contact), with
      the spraying method being the most effective. The methanolic extract of C.
      officinale showed both contact and fumigant activities, though only fumigant
      activity was observed with (Z)-ligustilide. The fumigant effects of the
      methanolic extract and (Z)-ligustilide caused 86.5 and 62.6% mortality,
      respectively, of D. gallinae adults at 48 h. Among (Z)-ligustilide, acaricides
      (bifenthrin, cypermethrin and spinosad) and butylidenephthalide, bifenthrin
      displayed the highest acaricidal activity, and the activity of
      butylidenephthalide was 2.3-fold higher than that of (Z)-ligustilide. These
      results suggest that C. officinale-derived material can be used for the
      development of a control agent for D. gallinae.

PMID- 29569075
TI  - Contrasting structures of plant-mite networks compounded by phytophagous and
      predatory mite species.
AB  - Differences in the feeding habits between phytophagous and predatory species can
      determine distinct ecological interactions between mites and their host plants.
      Herein, plant-mite networks were constructed using available literature on plant
      dwelling mites from Brazilian natural vegetation in order to contrast
      phytophagous and predatory mite networks. The structural patterns of plant-mite
      networks were described through network specialization (connectance) and
      modularity. A total of 187 mite species, 65 host plant species and 646
      interactions were recorded in 14 plant-mite networks. Phytophagous networks
      included 96 mite species, 61 host plants and 277 interactions, whereas predatory
      networks contained 91 mite species, 54 host plants and 369 interactions. No
      differences in the species richness of mites and host plants were observed
      between phytophagous and predatory networks. However, plant-mite networks
      composed of phytophagous mites showed lower connectance and higher modularity
      when compared to the predatory mite networks. The present results corroborate the
      hypothesis that trophic networks are more specialized than commensalistic
      networks, given that the phytophagous species must deal with plant defenses, in
      contrast to predatory mites which only inhabit and forage for resources on
      plants.

PMID- 29569076
TI  - Serious mental illness and negative substance use consequences among adults on
      probation.
AB  - BACKGROUND: Adults on probation are at greater risk of both using substances and
      having a mental disorder compared to the general population. Several theories
      explain the relationship between substance use and poor mental health. However,
      the interaction between substance use, mental health, and substance-related
      consequences is not well understood. A better understanding of this relationship
      may help treatment programs become more responsive to people with serious mental
      illness (SMI). METHOD: The current study used interview data from 313 adults on
      probation who reported recent substance use. We examined associations between SMI
      risk, substance use, and substance use consequences. RESULTS: A substantial
      proportion of the sample (37.5%) screened at risk of having a SMI. Adjusting for
      type and amount of substance use, those who screened at risk of having a SMI
      reported more negative substance use consequences. Significant interaction
      effects were observed between use of alcohol or opiates and SMI risk. Alcohol use
      was associated with more negative substance use consequences among those at risk
      of SMI, while opiate use was associated with more consequences among those not at
      risk. CONCLUSIONS: Programs are sorely needed to identify and treat adults with
      comorbid substance use and mental health symptoms, particularly for adults in the
      justice system. Clinicians should carefully consider how mental health may
      interact with substance use to exacerbate consequences.

PMID- 29569078
TI  - Anemia Due to ABO Incompatibility in a Neonate.

PMID- 29569077
TI  - Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated
      by cAMP-Epac Pathway.
AB  - Quercetin (Que) as an abundant flavonol element possesses potent antioxidative
      properties and has protective effect in lipopolysaccharide (LPS)-induced acute
      lung injury (ALI), but the specific mechanism is still unclear, so we
      investigated the effect of Que from in vivo and in vitro studies and the related
      mechanism of cAMP-PKA/Epac pathway. The results in mice suggested that Que can
      inhibit the release of inflammatory cytokine, block neutrophil recruitment, and
      decrease the albumin leakage in dose-dependent manners. At the same time, Que can
      increase the cAMP content of lung tissue, and Epac content, except PKA. The
      results in epithelial cell (MLE-12) suggested that Que also can inhibit the
      inflammatory mediators keratinocyte-derived chemokines release after LPS
      stimulation; Epac inhibitor ESI-09 functionally antagonizes the inhibitory effect
      of Que; meanwhile, PKA inhibitor H89 functionally enhances the inhibitory effect
      of Que. Overexpression of Epac1 in MLE-12 suggested that Epac1 enhance the effect
      of Que. All those results suggested that the protective effect of quercetin in
      ALI is involved in cAMP-Epac pathway.

PMID- 29569079
TI  - Exercise Capacity Assessment by the Modified Shuttle Walk Test and its
      Correlation with Biochemical Parameters in Obese Children and Adolescents.
AB  - OBJECTIVES: To evaluate exercise capacity of obese children and adolescents
      compared with normal-weight individuals and to investigate possible correlations
      with blood biochemical parameters. METHODS: In this study, children and
      adolescents between 6 and 18 y were included and divided into control (eutrophic)
      and obese groups according to body mass index (BMI). Data were collected
      regarding demographic, anthropometric, waist circumference and exercise capacity
      through the Modified Shuttle Walk Test (MSWT). In the obese group, biochemical
      parameters in the blood (total cholesterol, HDL, LDL, triglycerides and glucose)
      were evaluated, and a physical activity questionnaire was applied. RESULTS:
      Seventy seven participants were included; 27 in the control group and 50 obese.
      There was no significant difference between the two groups regarding sample
      characteristics, except for body weight, BMI and waist circumference. Most obese
      children presented results of biochemical tests within the desirable limit,
      though none were considered active. There was a significant exercise capacity
      reduction (p < 0.001) in the obese group compared to control subjects. Positive
      correlations were identified for the MSWT with age and height, and a negative
      correlation with BMI. However, there were no correlations with the biochemical
      parameters analyzed. CONCLUSIONS: Obese children and adolescents have reduced
      exercise capacity when compared to normal individuals. The MSWT performance seems
      to have a negative association with BMI, but is not correlated with blood
      biochemical parameters.

PMID- 29569080
TI  - Acute Encephalitis Syndrome: Current Trends and the Future.

PMID- 29569081
TI  - Identification of a melatonin receptor type 1A gene (AccMTNR1A) in Apis cerana
      cerana and its possible involvement in the response to low temperature stress.
AB  - It is known that melatonin plays an indispensable role in the defense against
      some environment-induced stresses. The melatonin receptor (MTNR) is also closely
      linked to the environmental stress response in mammals. However, little is known
      about the function of the MTNR in insects, including honeybees. In this study, we
      identified a MTNR from Apis cerana cerana named AccMTNR1A, which contained a
      typical seven-transmembrane domain common to this family of receptors. A
      subcellular localization analysis showed that AccMTNR1A was localized in the
      cytomembrane. Additionally, we found that cold stress apparently boosted
      AccMTNR1A transcription, indicating that AccMTNR1A possibly connects to the cold
      stress response. The knockdown of AccMTNR1A attenuated the expression level of
      some genes associated with the cold stress response, suggesting that AccMTNR1A
      likely plays an analogous role with these genes during low temperature stress
      response. Moreover, silencing of AccMTNR1A also suppressed the transcription of
      some antioxidant genes, prompting the possibility that the response of AccMTNR1A
      to cold stress response may be related to antioxidant signaling pathways.
      Collectively, the findings presented here provide evidence that AccMTNR1A may
      play essential roles in protecting Apis cerana cerana from cold stress.

PMID- 29569082
TI  - Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison
      Between Agents.
AB  - Schizophrenia is a chronic medical condition with periods of remission and
      relapses over a patient's lifetime. Antipsychotic medications represent the
      mainstay of treatment for this disease. Long-acting injectable (LAI) formulations
      of antipsychotics are an attractive alternative to their oral counterparts, as
      they enhance patient adherence. A number of second-generation antipsychotics
      (SGAs) are available in LAI formulations. These include paliperidone,
      aripiprazole, olanzapine, and risperidone. This article reviews the most recently
      developed and approved of these formulations-aripiprazole monohydrate,
      aripiprazole lauroxil, and paliperidone palmitate. While all were initially
      available as once-monthly formulations, a paliperidone palmitate 3-monthly
      injection formulation has been approved and is the first LAI agent to extend the
      dosing administration beyond the typical monthly time period. In addition,
      aripiprazole lauroxil every 6-week and 8-week administration preparations have
      been developed. LAI preparations of the SGAs have all demonstrated superiority
      over placebo and are comparable to their oral counterparts in terms of safety and
      tolerability, if injection site reactions are not taken into account. First
      generation antipsychotic LAI preparations (e.g., haloperidol decanoate) have
      recently been compared with SGA LAI agents, and both formulations demonstrated
      comparable efficacy with the expected adverse events seen with each drug. Despite
      their availability, barriers to the use of LAIs remain. Education of both
      patients and clinicians on the use of LAI formulations and the continued
      development of these agents are important steps in ensuring these medications are
      available to the patients they would be most likely to benefit.

PMID- 29569083
TI  - Attention-deficit/hyperactivity disorder children exhibit an impaired
      accommodative response.
AB  - PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) is one of the most
      common paediatric neurobehavioural disorders causing multiple functional
      impairments in children. Based on the relationship between the neural system that
      controls attention and ocular dynamics, the present study compares the magnitude
      and variability of accommodation between a group of non-medicated ADHD children
      and an age-matched control group. METHODS: The magnitude and variability of the
      accommodative response were objectively measured in 36 children using the WAM
      5500 autorefractometer for 90 consecutive seconds at three static viewing
      distances (500, 40, and 20 cm). Participants were divided into ADHD (n = 18) or
      control (n = 18) groups based on clinically validated criteria. RESULTS: Children
      with ADHD exhibited higher lags of accommodation (p = 0.024), increasing at
      closer viewing distances, in comparison to the control group. Marginal
      statistical differences were found for the variability of accommodation (p =
      0.066), with the ADHD group showing a trend towards higher variability. Our
      analysis showed that the magnitude and variability of accommodation did not vary
      over time between groups (p > 0.05). CONCLUSIONS: Our data suggest that children
      with ADHD have a less accurate accommodative response. These results provide a
      new ocular index that could help to clarify the relationship between
      accommodative response and attentional deficits, which could have a direct impact
      on the academic, cognitive, and visual performance of ADHD children.

PMID- 29569084
TI  - Screening organometallic thiophene containing thiosemicarbazone ruthenium
      (II/III) complexes as potential anti-tumour agents.
AB  - The new ruthenium (III) complex has been synthesized and characterized by
      elemental analysis, FT-IR, UV-Vis, EI-Mass, EPR spectroscopy, and magnetic
      susceptibility measurement. Cytotoxic effects of organoruthenium (II/III)
      complexes 1a, 1b, and 2a, and their ligands (TSC1 and TSC2) in cultured human
      ovarian (A2780, SKOV-3, and OVCAR-3) and colon (DLD, CCD18Co, and Caco-2) cells
      have been investigated comparing reactivity of the Ru (II/III) complexes and
      their free TSC ligands. The complexes exhibit higher cytotoxicity in three cancer
      cell lines than in normal cells. The binding with CT-DNA and BSA of the all
      complexes were weak compared with their ligand in spite of the cellular uptake of
      these complexes into the cytoplasm and then nucleus while their cytotoxic effects
      were vice versa. All the results showed that Complex 1b has more efficient
      cytotoxicity on the colon cancer cells than ovarian cancer cells. However,
      Complex 2a is a better drug candidate especially for antitumor therapy of
      metastasized ovarian cancer.

PMID- 29569086
TI  - Pediatric cerebellar pilocytic astrocytoma presenting with spontaneous
      intratumoral hemorrhage.
AB  - Pilocytic astrocytomas (PAs) are benign glial tumors and one of the most common
      childhood posterior fossa tumors. Spontaneous intratumoral hemorrhage in PAs
      occurs occasionally, in about 8-20% of cases. Cerebellar hemorrhages in pediatric
      population are rare and mainly due to head injuries, rupture of vascular
      malformations, infections, or hematological diseases. We have investigated the
      still controversial and unclear pathophysiology underlying intratumoral
      hemorrhage in PAs. Bleeding in low-grade tumors might be related to structural
      abnormalities and specific angio-architecture of tumor vessels, such as
      degenerative mural hyalinization, "glomeruloid" endothelial proliferation,
      presence of encased micro-aneurysms, and glioma-induced neoangiogenesis. The
      acute hemorrhagic presentation of cerebellar PA in childhood although extremely
      uncommon is of critical clinical importance and necessitates promptly treatment.
      We described a case of hemorrhagic cerebellar PA in a 9-year-old child and
      reviewed the English-language literature that reported spontaneous hemorrhagic
      histologically proven cerebellar PA in pediatric patients (0-18 years). According
      to our analysis, the mortality was not related to symptom onset, tumor location,
      hemorrhage distribution, presence of acute hydrocephalous, and timing of surgery,
      while the GCS at hospital admission resulted to be the only statistically
      significant prognostic factor affecting survival outcome. The abrupt onset of
      signs and symptoms of acute hydrocephalous and consequent raised intracranial
      pressure are life-threatening conditions, which need emergent medical and
      neurosurgical treatments. At a later time, the identification of posterior fossa
      hemorrhage etiology is crucial to select the appropriate treatment and address
      the surgical strategy, optimizing the postoperative results.

PMID- 29569087
TI  - Reversal of retinal pigment epithelial detachment after cessation of topical
      travoprost therapy.
AB  - PURPOSE: To report the rare incidence of retinal pigment epithelial detachment
      (RPED) followed by topical travoprost therapy and its subsequent reattachment
      after cessation of the drug. METHODS: A 60-year-old male presented with gradual
      loss of vision in both eyes and distorted images in right eye. He gave a history
      of visiting an ophthalmologist a week ago for a routine eye examination. His
      previous reports revealed best-corrected visual acuity (BCVA) of 6/6, N6 in both
      eyes with raised intraocular pressures. A diagnosis of primary open-angle
      glaucoma was made and prescribed topical travoprost 0.004% eye drops. This
      patient's subsequent visit with diagnosis and treatment is mentioned in this case
      report. RESULTS: On examination, his BCVA was found to be 6/36, N12 and 6/6, N6
      in right and left eyes, respectively. Optical coherence tomography (OCT) macular
      scan revealed RPED involving fovea in the right eye and inferotemporal to fovea
      in the left eye. Patient was advised to discontinue topical travoprost and
      started brinzolamide 1% eye drops. Ten-day follow-up visit revealed partially
      resolved RPED by OCT with 6/9 and 6/6 visual acuity in the right and left eyes,
      respectively. After 1 month, reversal of RPED was noted in OCT with 6/6 vision in
      both eyes. CONCLUSION: Hence, clinicians should be aware of this rare incidence
      of RPED followed by travoprost therapy. First case of RPED following travoprost
      therapy and complete reattachment upon withdrawal is reported here in this case
      report.

PMID- 29569085
TI  - The NMR contribution to protein-protein networking in Fe-S protein maturation.
AB  - Iron-sulfur proteins were among the first class of metalloproteins that were
      actively studied using NMR spectroscopy tailored to paramagnetic systems. The
      hyperfine shifts, their temperature dependencies and the relaxation rates of
      nuclei of cluster-bound residues are an efficient fingerprint of the nature and
      the oxidation state of the Fe-S cluster. NMR significantly contributed to the
      analysis of the magnetic coupling patterns and to the understanding of the
      electronic structure occurring in [2Fe-2S], [3Fe-4S] and [4Fe-4S] clusters bound
      to proteins. After the first NMR structure of a paramagnetic protein was obtained
      for the reduced E. halophila HiPIP I, many NMR structures were determined for
      several Fe-S proteins in different oxidation states. It was found that
      differences in chemical shifts, in patterns of unobserved residues, in internal
      mobility and in thermodynamic stability are suitable data to map subtle changes
      between the two different oxidation states of the protein. Recently, the
      interaction networks responsible for maturing human mitochondrial and cytosolic
      Fe-S proteins have been largely characterized by combining solution NMR standard
      experiments with those tailored to paramagnetic systems. We show here the
      contribution of solution NMR in providing a detailed molecular view of "Fe-S
      interactomics". This contribution was particularly effective when protein-protein
      interactions are weak and transient, and thus difficult to be characterized at
      high resolution with other methodologies.

PMID- 29569089
TI  - Author Correction: Clinical chameleons: an emergency medicine focused review of
      carbon monoxide poisoning.
AB  - In the original publication, first author's name was incorrectly published as
      'Patrick Chow Yuen Ng' instead of 'Patrick Chow Ng'.

PMID- 29569088
TI  - Visceral adiposity index (VAI), a powerful predictor of incident hypertension in
      prehypertensives.
AB  - Prehypertension (defined by The Seventh Report of the Joint National Committee on
      the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, JNC
      7) is relevant to a higher cardiovascular risk than normotensives. Early
      intervention in this particular population is essential to avoid progression into
      hypertension (HTN). This study is to explore whether visceral adiposity index
      (VAI) can strongly predict the incidence of HTN in community-based
      prehypertensives. A prospective observational cohort study was conducted from
      September 2011 to June 2012 in urban communities of Chengdu, Sichuan Province,
      China. 780 subjects (male 320, female 460) were evaluated on anthropometrical
      indices, blood pressure, blood samples, brachial-ankle pulse wave velocity, of
      whom 360 prehypertensives (male 160, female 200) were recruited for a 5-year
      follow-up. Overall, 97 subjects (male 37, female 60) developed HTN. The risk for
      developing HTN in the future increases with increasing VAI levels. The OR of the
      upper quartile is 3.719 (95% CI 1.481-9.338, P = 0.005) after adjusting for
      confounders. The ROC results reveal that VAI is not considered superior to other
      indices on account of the significant overlapping confidence intervals. The area
      under the curves (AUC) of Model 5 (combination of VAI and WC) is significantly
      higher than BMI, WC and WHR (P < 0.05). The AUC of Model 4 (combination of VAI
      and BMI) is found to be significantly higher than BMI and WHR (P < 0.05), and is
      also higher than WC in all subject groups and in the male subgroup, but not in
      the female subgroup. VAI at baseline is an independent risk factor and early
      predictor of incident HTN in prehypertensives. The predictive value is not
      stronger than other traditional obesity indices (BMI, WC and WHR); however, it is
      superior to the latter by combining VAI and WC. Namely, VAI may help identify
      individuals at high risk of evolving into HTN in this particular population.

PMID- 29569090
TI  - Author Correction: Toxic alcohol diagnosis and management: an emergency medicine
      review.
AB  - Toxic alcohols are a group of substances containing a hydroxyl group not meant to
      be ingested. They are the cause of a significant number of accidental and non
      accidental exposures. Toxic alcohol poisoning can be associated with a
      significant degree of morbidity and mortality if not promptly recognized and
      treated. This review describes the clinical presentation and an approach to the
      recognition and management for toxic alcohol poisoning. Toxic alcohols
      classically refer to a group of alcohols not meant for ingestion. Methanol,
      ethylene glycol, and isopropyl alcohol are readily available in common hardware
      and household materials. Toxic alcohols are ingested for a variety of reasons
      including accidental exposures, intentional inebriation, homicide and suicide.
      The patient with an altered mental status or concerning history warrants
      consideration of this potentially deadly ingestion. Treatment considerations
      include alcohol dehydrogenase blockade and hemodialysis. Toxic alcohol poisoning
      can be an elusive diagnosis. This review evaluates toxic alcohol poisoning signs
      and symptoms and an approach to diagnosis and management.

PMID- 29569091
TI  - Increasing levels of supplementation for crossbred steers on pasture during the
      dry period of the year.
AB  - The aim of this study was to evaluate the effect of increasing concentrate
      supplementation levels on the intake, nutrient digestibility, and performance of
      crossbred steers during the dry period of the year. The experiment was developed
      on Princesa do Mateiro farm, in the municipality of Ribeirao do Largo, located in
      the southwest region of Bahia State, Brazil. Forty uncastrated male crossbred
      (1/2 Holstein-Zebu) steers with an average body weight (BW) of 232.55 +/- 24.97
      kg were distributed into four treatments in a completely randomized design with
      ten replicates. The animals were managed in an experimental area formed by
      Brachiaria brizantha cv. Marandu, in an intermittent grazing system. Treatments
      consisted of the following supplementation levels: 0.2% BW, with 60% crude
      protein (CP); 0.3% BW, with 40% CP; 0.4% BW, with 30% CP; and 0.5% BW, with 24%
      CP. The intakes of forage dry matter in kg/day and %BW and neutral detergent
      fiber corrected for ash and protein (NDFap) in %BW decreased linearly, whereas
      the intake of non-fibrous carbohydrates corrected for ash and protein in kg/day
      and average daily gain increased linearly. Therefore, the use of supplementation
      at 0.5% BW (24% crude protein) to provide gains of up to 0.500 kg/day is
      recommended for grazing steers during the post-weaning period in the dry season
      of the year.

PMID- 29569092
TI  - The impact of health on wages: evidence for Europe.
AB  - This paper analyses the effects of health on wages in sixteen European countries
      using production frontier methodology. It is assumed that workers have a
      potential income/productivity which basically depends on their human capital, but
      due to several health problems, situations could exist where workers fail to
      reach their potential income frontier. The estimation of a true-random-effects
      model allows us to conclude that the potential hourly wage of workers is
      significantly influenced by their level of education and their job experience.
      However, health problems, especially those strongly influencing work activities,
      contribute towards an individual not attaining the potential income which would
      otherwise be guaranteed by their human capital endowment. Suffering a strong
      limitation reduces gross wage per hour by 6.1%. This wage reduction is also
      observed in the case of a weak limitation, but here the wage difference with
      respect to workers without any limitation is 2.6%. Additionally, other factors,
      such as being a woman, the economic cycle or having a temporary contract, appear
      to distance an individual from their wage frontier.

PMID- 29569093
TI  - Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With
      Direct-acting Antiviral Therapy.
AB  - PURPOSE OF REVIEW: The approval of direct-acting antiviral (DAA) therapy has
      revolutionized hepatitis C virus (HCV) treatment. However, the publication of a
      study from Barcelona in 2016 raised concern for an increased risk of recurrence
      of hepatocellular carcinoma (HCC) after potentially curative therapy in patients
      receiving DAAs. This article reviews the current literature on the interaction
      between HCC and hepatitis C eradication with DAAs. RECENT FINDINGS: Following
      publication of the initial observation in 2016, a number of studies have looked
      at the impact of active HCC on the success of antiviral therapy, as well as that
      of treatment with DAAs on both the occurrence and recurrence of HCC. The presence
      of active HCC decreases sustained virologic response (SVR) rates with DAAs.
      However, SVR rates improve in patients who have achieved complete radiological
      response or are treated post transplantation. With respect to occurrence of HCC
      after DAAs, many small single-center studies without a control group have
      documented high incidence. The rates are also higher when compared to those of
      historical controls treated with interferon, but these patients are not
      comparable because DAA-treated population is more likely to have advanced
      fibrosis or decompensation. In large studies that have included a control group
      (patients treated concurrently who did not achieve SVR), a decrease in the
      occurrence of HCC has been demonstrated. With regard to recurrence of HCC, while
      smaller single-center studies have shown an increase, larger studies with control
      group have not replicated those findings. However, methodological limitations in
      the published studies limit our ability to make a firm conclusion on both the
      occurrence and recurrence of HCC after DAA therapy. The presence of active HCC
      decreases treatment success rates with DAAs. Therefore, it is recommended that
      treatment of HCV in patients with HCC be deferred till there is complete
      radiological response. Though there are major limitations with the currently
      published studies, the data does not support an increase in the occurrence or
      recurrence of HCC after DAA therapy.

PMID- 29569094
TI  - Focal intra-cavotricuspid isthmus atrial tachycardias occurring after typical
      atrial flutter ablation: incidence and electrocardiographic and
      electrophysiological characteristics.
AB  - PURPOSE: Focal atrial tachycardias (ATs) from the septal cavotricuspid isthmus
      (CTI) occurring after successful CTI ablation can mimic typical atrial flutter
      (tAFL). This study investigated the incidence, and electrocardiographic and
      electrophysiological characteristics of these ATs. METHODS: Among 1082
      consecutive patients undergoing successful CTI ablation without any congenital
      heart diseases, 7 were diagnosed with focal ATs originating from the septal CTI
      that occurred a median of 74 days after the CTI ablation. RESULTS: The
      electrocardiographic characteristics of the ATs were similar to those of the
      tAFLs. The AT's cycle length was never shorter than and often similar to that of
      tAFLs. The activation patterns along the tricuspid annulus during the ATs were
      the same as those of tAFLs in 4 patients with foci adjacent to the CTI line, and
      centrifugal from foci around the coronary sinus (CS) ostium in 3. Entrainment
      pacing from the lateral CTI during the ATs revealed a manifest fusion and long
      post-pacing interval. Entrainment pacing from the lateral CTI during the ATs
      revealed that the atrial electrograms recorded from the CS and high-lateral right
      atrium were orthodromically captured, while that from the proximal CS revealed
      that the atrial electrograms recorded from the CS and lateral right atrium were
      antidromically captured without manifest fusion. CONCLUSIONS: Focal intra-CTI ATs
      with a microreentrant mechanism very rarely occurred after successful CTI
      ablation. The electrocardiographic and electrophysiological characteristics of
      these ATs were similar to those of tAFLs. Overdrive pacing from the lateral CTI
      and proximal CS was helpful for distinguishing these ATs from recurrent tAFLs.

PMID- 29569095
TI  - Interventions and Strategies to Improve Oral Anticoagulant Use in Patients with
      Atrial Fibrillation: A Systematic Review of Systematic Reviews.
AB  - INTRODUCTION: Anticoagulation therapy is the fundamental approach for stroke
      prevention in atrial fibrillation (AF) patients. Numerous systematic reviews
      comparing anticoagulation strategies have been published. We aim to summarize the
      efficacy and safety evidence of these strategies in AF patients from previously
      published systematic reviews. METHODS: We searched PubMed, EMBASE and Cochrane
      library from inception to Feb 24th, 2017, to identify systematic reviews and meta
      analyses of randomized controlled trials that assessed interventions or
      strategies to improve oral anticoagulant use in AF patients. RESULTS: Thirty-four
      systematic reviews were eligible for inclusion but only 11 were included in the
      qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining
      systematic reviews had overlapping primary studies. There was insufficient
      evidence to support the efficacy of genotype-guided dosing and pharmacist-managed
      anticoagulation clinics for stroke prevention in AF patients. Conversely,
      patient's self-management and novel oral anticoagulants (NOACs), in general were
      superior to warfarin for preventing stroke and reducing mortality. All
      interventions showed comparable risk of major bleeding with warfarin. CONCLUSION:
      Findings from this overview support the superiority of NOACs and patient's self
      management for preventing stroke in AF patients. However, uncertainties remain on
      the benefits of genotype-guided dosing and pharmacist-managed anticoagulation
      clinics due to poor quality evidence, and future research is warranted.

PMID- 29569096
TI  - Did Antonio Vallisneri (1661-1730) really describe frontal sinus osteoma?
      Unexpected insights for paleo-neuroparasitology.
AB  - It has been believed for a long time that the Paduan scholar Antonio Vallisneri
      (1661-1730) described the second historical case of the frontal sinus osteoma in
      1733. By historico-medically reexamining this case, we conclude that the brain
      concretions he described were not a case of frontal sinus osteoma, while they
      appear to have been pathological outcomes of neurocysticercosis, whose larval
      stages would only be described by Johann Goeze (1731-1793) later, in 1784. Thus,
      this case becomes relevant for the history of neuroparasitology.

PMID- 29569098
TI  - Strong and Weak Readings in the Domain of Worlds: A Negative Polar Modal and
      Children's Scope Assignment.
AB  - This study investigates children's interpretation of sentences with two logical
      operators: Dutch universal modal hoeven and negation (niet). In adult Dutch,
      hoeven is an NPI that necessarily scopes under negation, giving rise to a NOT >
      NECESSARY reading. The findings from a hidden-object task with 5- and 6-year-old
      children showed that children's performance is suggestive of an interpretation of
      sentences with hoeft niet in which the modal scopes over negation (NECESSARY >
      NOT). This is in line with the Semantic Subset Principle that dictates that
      children should opt for the strongest possible reading in case of potential scope
      ambiguities. The full pattern of results, however, seems to be determined, in
      addition, by a particular strategy children use when facing uncertainty called
      Premature Closure.

PMID- 29569097
TI  - Probing the antioxidant potential of phloretin and phlorizin through a
      computational investigation.
AB  - The structures and energetics of two dihydrochalcones (phloretin and its
      glycoside phlorizin) were examined with density functional theory, using the
      B3LYP, M06-2X, and LC-omega PBE functionals with both the 6-311G(d,p) and 6-311 +
      G(d,p) basis sets. Properties connected to antioxidant activity, i.e., bond
      dissociation enthalpies (BDEs) for OH groups and ionization potentials (IPs),
      were computed in a variety of environments including the gas-phase, n-hexane,
      ethanol, methanol, and water. The smallest BDEs among the four OH groups for
      phloretin (three for phlorizin) were determined (using B3LYP/6-311 + G(d,p) in
      water) to be 79.36 kcal/mol for phloretin and 79.98 kcal/mol for phlorizin while
      the IPs (at the same level of theory) were obtained as 139.48 and 138.98
      kcal/mol, respectively. By comparing with known antioxidants, these values for
      the BDEs indicate both phloretin and phlorizin show promise for antioxidant
      activity. In addition, the presence of the sugar moiety has a moderate (0-6
      kcal/mol depending on functional) effect on the BDEs for all OH groups.
      Interestingly, the BDEs suggest that (depending on the functional chosen) the
      sugar moiety can lead to an increase, decrease, or no change in the antioxidant
      activity. Therefore, further experimental tests are encouraged to understand the
      substituent effect on the BDEs for phloretin and to help determine the most
      appropriate functional to probe BDEs for dihydrochalcones.

PMID- 29569099
TI  - Transanal total mesorectal excision for rectal cancer: evaluation of the learning
      curve.
AB  - BACKGROUND: Transanal total mesorectal excision (TaTME) provides an excellent
      view of the resection margins for rectal cancer from below, but is challenging
      due to few anatomical landmarks. During implementation of this technique, patient
      safety and optimal outcomes need to be ensured. The aim of this study was to
      evaluate the learning curve of TaTME in patients with rectal cancer in order to
      optimize future training programs. METHODS: All consecutive patients after TaTME
      for rectal cancer between February 2012 and January 2017 were included in a
      single-center database. Influence of surgical experience on major postoperative
      complications, leakage rate and operating time was evaluated using cumulative sum
      charts and the splitting model. Correction for potential case-mix differences was
      performed. RESULTS: Over a period of 60 months, a total of 138 patients were
      included in this study. Adjusted for case-mix, improvement in postoperative
      outcomes was clearly seen after the first 40 patients, showing a decrease in
      major postoperative complications from 47.5 to 17.5% and leakage rate from 27.5
      to 5%. Mean operating time (42 min) and conversion rate (from 10% to zero) was
      lower after transition to a two-team approach, but neither endpoint decreased
      with experience. Readmission and reoperation rates were not influenced by
      surgical experience. CONCLUSIONS: The learning curve of TaTME affected major
      (surgical) postoperative complications for the first 40 patients. A two-team
      approach decreased operative time and conversion rate. When implementing this new
      technique, a thorough teaching and supervisory program is recommended to shorten
      the learning curve and improve the clinical outcomes of the first patients.

PMID- 29569100
TI  - Acculturation and Unmet Health Needs Among Refugees in Omaha, Nebraska.
AB  - This study assessed the association between acculturation and unmet health needs
      among refugees. Based on data from the Refugee Health Needs Assessment Survey (n
      = 291) recently conducted in Omaha, Nebraska, Chi square tests and multivariate
      logistic regressions were estimated to examine how acculturation among refugees
      was related to their unmet health needs. Relative to refugees who had been in the
      U.S. for less than 3 years, refugees who had been in the U.S. for 3-5 years were
      more likely to report lack of health insurance coverage (AOR 2.87, 95% CI 1.19,
      6.92) and delaying to see a health care provider due to cost during the 12 months
      prior to the survey (AOR 4.01, 95% CI 1.18, 13.67). Acculturation among refugees
      did not necessarily alleviate their unmet health needs. Addressing these needs
      calls for sustainable medical assistance to refugees that well go beyond the 8
      month health insurance coverage currently provided to newly arrived refugees.

PMID- 29569101
TI  - Depressive and Anxiety Symptoms in Dutch Immigrant and Native Dialysis Patients.
AB  - Due to continuing migration there is more interest in the mental health status of
      immigrants. The aim of this study is to determine the prevalence of
      depressive/anxiety symptoms in immigrant and native dialysis patients, and to
      explore if patient characteristics can explain differences. The Beck depression
      inventory and the beck anxiety inventory were used. Differences between native
      and immigrant patients were explored using logistic regression models adjusted
      for patient characteristics. The prevalence of depressive symptoms was 35% for
      245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety
      symptoms was 35% for native patients and 50% for immigrant patients. In addition,
      the prevalence for co-morbid depressive and anxiety symptoms was 20% for native
      patients and 32% for immigrant patients. Crude ORs for depressive/anxiety
      symptoms for immigrant patients versus native patients were 1.8 (1.2-2.5) and 1.7
      (1.2-2.5), respectively. After adjustment for patient characteristics ORs
      remained the same. Clinicians should be aware that immigrant dialysis patients
      are more prone to develop depressive and anxiety symptoms. Cultural factors might
      play a role and should therefore be assessed in future research.

PMID- 29569102
TI  - Acculturation and Adherence to Physical Activity Recommendations Among Chinese
      American and Non-Hispanic White Breast Cancer Survivors.
AB  - Chinese American breast cancer survivors' adherence to recommended physical
      activity (PA) guidelines has been understudied. This study investigated their PA
      adherence by acculturation level (vs. non-Hispanic White (NHW) survivors). One
      hundred ninety five Chinese and 202 NHW breast cancer survivors (stage 0-III)
      responded to a cross-sectional survey including a self-reported PA questionnaire.
      PA adherence referred to meeting PA recommendations for cancer survivors.
      Acculturation among Chinese was defined by proxies of U.S. residency, English
      proficiency, and interview language. Logistic regression was performed to examine
      factors associated with PA adherence. More-acculturated Chinese survivors' PA
      adherence rate was 76%. Less-acculturated Chinese survivors' adherence rate (60%)
      was significantly lower than that of NHWs (80%) (OR 0.38, 95%CI 0.19, 0.75). Less
      acculturated Chinese survivors were also less likely to engage in vigorous
      intensity PA than NHWs (p < 0.01). Future research on less-acculturated Chinese
      survivors' motivation for PA to promote their adherence is needed.

PMID- 29569103
TI  - Acute myeloid leukemia with translocation (1;21).
AB  - Advancement in genetic and molecular biology techniques has greatly helped our
      understanding of various diseases, especially hematological disorders. We
      describe a case of primary myelofibrosis (PMF) that transformed into acute
      myeloid leukemia with a very rare and unusual genetic translocation of (1;21).
      There are only five reported cases of this translocation in acute myeloid
      leukemia (AML) or myelodysplastic syndrome but none of them transformed from PMF.
      This case not only highlights the importance of rare genetic translocations but
      also provides the natural history of the disease and its poor prognosis. To the
      best of our knowledge our patient is the first reported case of AML transformed
      from PMF to have this unique translocation of (1;21).

PMID- 29569105
TI  - Bounding measures of genetic similarity and diversity using majorization.
AB  - The homozygosity and the frequency of the most frequent allele at a polymorphic
      genetic locus have a close mathematical relationship, so that each quantity
      places a tight constraint on the other. We use the theory of majorization to
      provide a simplified derivation of the bounds on homozygosity J in terms of the
      frequency M of the most frequent allele. The method not only enables simpler
      derivations of known bounds on J in terms of M, it also produces analogous bounds
      on entropy statistics for genetic diversity and on homozygosity-like statistics
      that range in their emphasis on the most frequent allele in relation to other
      alleles. We illustrate the constraints on the statistics using data from human
      populations. The approach suggests the potential of the majorization method as a
      tool for deriving inequalities that characterize mathematical relationships
      between statistics in population genetics.

PMID- 29569106
TI  - NMR assignment and solution structure of the external DII domain of the yeast
      Rvb2 protein.
AB  - We report the nearly complete 1H, 15N and 13C resonance assignment and the
      solution structure of the external DII domain of the yeast Rvb2 protein, a member
      of the AAA+ATPase superfamily.

PMID- 29569107
TI  - Two new species of the Fusarium solani species complex isolated from compost and
      hibiscus (Hibiscus sp.).
AB  - Two new species in the Fusarium solani species complex (FSSC) are described and
      introduced. The new taxa are represented by German isolates CBS 142481 and CBS
      142480 collected from commercial yard waste compost and vascular tissue of a
      wilting branch of hibiscus, respectively. The phylogenetic relationships of the
      collected strains to one another and within the FSSC were evaluated based on DNA
      sequences of 6 gene loci. Due to the limited sequence data available for
      reference strains in GenBank, however, a multi-gene phylogenetic analysis
      included partial sequences for the internal transcribed spacer region and
      intervening 5.8S nrRNA gene (ITS), translation elongation factor 1-alpha (tef1)
      and the RNA polymerase II second largest subunit (rpb2). Morphological and
      molecular phylogenetic data independently showed that these strains are distinct
      populations of the FSSC, nested within Clade 3. Thus, we introduce Fusarium
      stercicola and Fusarium witzenhausenense as novel species in the complex. In
      addition, 19 plant species of 7 legume genera were evaluated for their potential
      to host the newly described taxa. Eighteen plant species were successfully
      colonized, with 6 and 9 of these being symptomatic hosts for F. stercicola and F.
      witzenhausenense, respectively. As plants of the family Fabaceae are very distant
      to the originally sourced material from which the new taxa were recovered, our
      results suggest that F. stercicola and F. witzenhausenense are not host-specific
      and are ecologically fit to sustain stable populations in variety of habitats.

PMID- 29569104
TI  - Individualising Therapy to Minimize Bacterial Multidrug Resistance.
AB  - The scourge of antibiotic resistance threatens modern healthcare delivery. A
      contributing factor to this significant issue may be antibiotic dosing, whereby
      standard antibiotic regimens are unable to suppress the emergence of antibiotic
      resistance. This article aims to review the role of pharmacokinetic and
      pharmacodynamic (PK/PD) measures for optimising antibiotic therapy to minimise
      resistance emergence. It also seeks to describe the utility of combination
      antibiotic therapy for suppression of resistance and summarise the role of
      biomarkers in individualising antibiotic therapy. Scientific journals indexed in
      PubMed and Web of Science were searched to identify relevant articles and
      summarise existing evidence. Studies suggest that optimising antibiotic dosing to
      attain defined PK/PD ratios may limit the emergence of resistance. A maximum
      aminoglycoside concentration to minimum inhibitory concentration (MIC) ratio of >
      20, a fluoroquinolone area under the concentration-time curve to MIC ratio of >
      285 and a beta-lactam trough concentration of > 6 * MIC are likely required for
      resistance suppression. In vitro studies demonstrate a clear advantage for some
      antibiotic combinations. However, clinical evidence is limited, suggesting that
      the use of combination regimens should be assessed on an individual patient
      basis. Biomarkers, such as procalcitonin, may help to individualise and reduce
      the duration of antibiotic treatment, which may minimise antibiotic resistance
      emergence during therapy. Future studies should translate laboratory-based
      studies into clinical trials and validate the appropriate clinical PK/PD
      predictors required for resistance suppression in vivo. Other adjunct strategies,
      such as biomarker-guided therapy or the use of antibiotic combinations require
      further investigation.

PMID- 29569108
TI  - Rhodobacter sp. Rb3, an aerobic anoxygenic phototroph which thrives in the
      polyextreme ecosystem of the Salar de Huasco, in the Chilean Altiplano.
AB  - The Salar de Huasco is an evaporitic basin located in the Chilean Altiplano,
      which presents extreme environmental conditions for life, i.e. high altitude
      (3800 m.a.s.l.), negative water balance, a wide salinity range, high daily
      temperature changes and the occurrence of the highest registered solar radiation
      on the planet (> 1200 W m-2). This ecosystem is considered as a natural
      laboratory to understand different adaptations of microorganisms to extreme
      conditions. Rhodobacter, an anoxygenic aerobic phototrophic bacterial genus,
      represents one of the most abundant groups reported based on taxonomic diversity
      surveys in this ecosystem. The bacterial mat isolate Rhodobacter sp. strain Rb3
      was used to study adaptation mechanisms to stress-inducing factors potentially
      explaining its success in a polyextreme ecosystem. We found that the Rhodobacter
      sp. Rb3 genome was characterized by a high abundance of genes involved in stress
      tolerance and adaptation strategies, among which DNA repair and oxidative stress
      were the most conspicuous. Moreover, many other molecular mechanisms associated
      with oxidative stress, photooxidation and antioxidants; DNA repair and
      protection; motility, chemotaxis and biofilm synthesis; osmotic stress, metal,
      metalloid and toxic anions resistance; antimicrobial resistance and multidrug
      pumps; sporulation; cold shock and heat shock stress; mobile genetic elements and
      toxin-antitoxin system were detected and identified as potential survival
      mechanism features in Rhodobacter sp. Rb3. In total, these results reveal a wide
      set of strategies used by the isolate to adapt and thrive under environmental
      stress conditions as a model of polyextreme environmental resistome.

PMID- 29569109
TI  - A novel pigmented and heavy metal biosorptive bacterium, Leucobacter epilobiisoli
      sp. nov., isolated from rhizosphere soil of Epilobium hirsutum L.
AB  - A novel yellow pigmented, Gram-positive, aerobic and heavy metal biosorptive
      bacterium designated SYP-B2667T was isolated from rhizosphere soil of Epilobium
      hirsutum L. in Tongren, Guizhou province, China. Based on 16S rRNA gene sequence
      analyses, it was shown that strain SYP-B2667T represents a novel species in the
      genus Leucobacter, with Leucobacter chromiireducens subsp. solipictus JCM 15573T
      as a close phylogenetic neighbour (sequence similarity of 98.2%). Chemotaxonomic
      characteristics also supported the affiliation to the genus Leucobacter. Strain
      SYP-B2667T was determined to have a DNA G+C content of 66.6 mol%; 2,4
      diaminobutyric acid in the cell wall peptidoglycan amino acids; MK-11 as
      predominant menaquinone; an abundance of anteiso-C15:0 and anteiso-C17:0 fatty
      acids; and polar lipids including diphosphatidylglycerol, phosphatidylglycerol,
      glycolipids and unidentified phospholipids. The DNA-DNA hybridization value
      between strain SYP-B2667T and L. chromiireducens subsp. solipictus JCM 15573T was
      19.7 +/- 2.8%. Based on these phylogenetic and phenotypic results, it can be
      concluded that strain SYP-B2667T represents a novel species, for which the name
      Leucobacter epilobiisoli sp. nov. is proposed. The type strain is SYP-B2667T
      (=DSM 105145T=CPCC 204976T). This strain can tolerate and adsorb five heavy
      metals and so may have potential to facilitate heavy metal removal and
      bioremediation.

PMID- 29569110
TI  - Comparison of Attitudes Toward Death Between University Students Who Receive
      Nursing Education and Who Receive Religious Education.
AB  - This study aims to compare attitudes toward death between university students who
      receive nursing education and who receive religious education. This study is
      cross-sectional in nature. It was conducted with the participation of 197
      university students in a university located in the Eastern part of Turkey between
      June and August, 2017. Data were collected using the socio-demographic form and
      Turkish form of Death Attitudes Profile-Revised. Of all the students
      participating in the study, 52.8% received nursing education and 47.2% received
      religious education. It was found that majority of both groups had no education
      about death, or found the education they received insufficient. Besides, no
      significant differences were found between the students who received nursing
      education and who received religious education in terms of their attitudes toward
      death (p > 0.05). Results showed that students who received nursing education and
      who received religious education had similar attitudes toward death. In
      conclusion, the education given to students about the religious or health aspects
      of death in accordance with the curriculum seemed to have no effects on students'
      developing positive attitudes toward death.

PMID- 29569111
TI  - The Role of Healthcare Chaplains in Resuscitation: A Rapid Literature Review.
AB  - Spirituality is becoming of increasing importance in the international healthcare
      context. While patients' spirituality or faith is often overlooked, there is a
      growing awareness that understanding, addressing and supporting patients'
      spiritual and faith needs can influence healthcare outcomes. This review aims to
      illuminate this role and highlight healthcare chaplains' potential in relation to
      the provision of pastoral support for families during and after patient
      resuscitation, and the dearth of interdisciplinary education in this field. A
      rapid structured review was undertaken using four databases-PubMed, CINAHL,
      PsycINFO and ATLA. Primary research studies published during the 10-year period
      2007-2017 written in English addressing the chaplain's role or perceived role in
      resuscitation were included. An initial search using key terms yielded 18
      relevant citations. This reduced to 11 once duplicates were removed. Ultimately
      five relevant primary research studies were included in the final analysis. This
      review found few studies that directly explored the topic. Certainly many view
      the chaplain as a key member of the resuscitation team, although this role has
      not been fully explored. Chaplains likely have a key role in supporting families
      during decisions about 'not for resuscitation' and in supporting families during
      and after resuscitation procedures. Chaplains are key personnel, already employed
      in many healthcare organisations, who are in a pivotal position to contribute to
      future developments of spiritual and pastoral care provision and support. Their
      role at the end of life, despite well described and supported, has received
      little empirical support. There is an emerging role for chaplains in healthcare
      ethics, supporting end-of-life decisions and supporting family witnessed
      resuscitation where relevant. Their role needs to be more clearly understood by
      medical staff, and chaplain's input into undergraduate medical education
      programmes is becoming vital.

PMID- 29569113
TI  - Current status of postmastectomy radiation therapy in T1-2 breast cancer with
      limited positive lymph nodes in Japan: Japan Clinical Oncology Group Survey.

PMID- 29569114
TI  - The Phox Homology (PX) Domain.
AB  - The phox-homology (PX) domain is a phosphoinositide-binding domain conserved in
      all eukaryotes and present in 49 human proteins. Proteins containing PX domains,
      many of which are also known as sorting nexins (SNXs), have a large variety of
      functions in membrane trafficking, cell signaling, and lipid metabolism in
      association with membranes of the secretory and endocytic system. In this review
      we discuss the structural basis for both canonical lipid interactions with the
      endosome-enriched lipid phosphatidylinositol-3-phosphate (PtdIns3P) as well as
      non-canonical lipids that promote membrane association. We also describe recent
      advances in defining the diverse mechanisms by which PX domains interact with
      other proteins including the retromer trafficking complex and proteins secreted
      by bacterial pathogens. Like other membrane interacting domains, the attachment
      of PX domain proteins to specific membranes is often facilitated by additional
      interactions that contribute to binding avidity, and we discuss this coincidence
      detection for several known examples.

PMID- 29569112
TI  - Phenylephrine increases cardiac output by raising cardiac preload in patients
      with anesthesia induced hypotension.
AB  - Induction of general anesthesia frequently induces arterial hypotension, which is
      often treated with a vasopressor, such as phenylephrine. As a pure alpha-agonist,
      phenylephrine is conventionally considered to solely induce arterial
      vasoconstriction and thus increase cardiac afterload but not cardiac preload. In
      specific circumstances, however, phenylephrine may also contribute to an increase
      in venous return and thus cardiac output (CO). The aim of this study is to
      describe the initial time course of the effects of phenylephrine on various
      hemodynamic variables and to evaluate the ability of advanced hemodynamic
      monitoring to quantify these changes through different hemodynamic variables. In
      24 patients, after induction of anesthesia, during the period before surgical
      stimulus, phenylephrine 2 ug kg-1 was administered when the MAP dropped below 80%
      of the awake state baseline value for > 3 min. The mean arterial blood pressure
      (MAP), heart rate (HR), end-tidal CO2 (EtCO2), central venous pressure (CVP),
      stroke volume (SV), CO, pulse pressure variation (PPV), stroke volume variation
      (SVV) and systemic vascular resistance (SVR) were recorded continuously. The
      values at the moment before administration of phenylephrine and 5(T5) and 10(T10)
      min thereafter were compared. After phenylephrine, the mean(SD) MAP, SV, CO, CVP
      and EtCO2 increased by 34(13) mmHg, 11(9) mL, 1.02(0.74) L min-1, 3(2.6) mmHg and
      4.0(1.6) mmHg at T5 respectively, while both dynamic preload variables decreased:
      PPV dropped from 20% at baseline to 9% at T5 and to 13% at T10 and SVV from 19 to
      11 and 14%, respectively. Initially, the increase in MAP was perfectly aligned
      with the increase in SVR, until 150 s after the initial increase in MAP, when
      both curves started to dissociate. The dissociation of the evolution of MAP and
      SVR, together with the changes in PPV, CVP, EtCO2 and CO indicate that in
      patients with anesthesia-induced hypotension, phenylephrine increases the CO by
      virtue of an increase in cardiac preload.

PMID- 29569116
TI  - Longitudinal comparison of low- and high-velocity resistance training in relation
      to body composition and functional fitness of older adults.
AB  - BACKGROUND: Functional mobility disability affects more than one in five adults
      over 70 years and increases to 80% by 90 years. While negative changes in
      mobility are multifactorial, deleterious body composition changes contribute
      significantly. Resistance training alters the negative trajectory of physical
      function as well as increases lean mass among older adults. Recently, high
      velocity (HV) resistance training has been indicated as an effective intervention
      to increase lean mass and functional performance. AIMS: The present investigation
      compared body composition, physical function, and muscular strength changes
      between HV and LV resistance training programs. METHODS: Participants > 65 years
      (n = 53) were randomly assigned to LV, HV, or active control (AC) group and
      participated in their respective intervention for 48 weeks. RESULTS: Analysis of
      covariance revealed no significant body composition changes over time between
      groups (p > 0.05). Eight-foot up-and-go performance improved in the HV and AC
      groups (p < 0.05) with no change in the LV group (p > 0.05) over time. Muscular
      strength increased in both the LV and HV groups within the first 24 weeks, while
      only in the LV group, muscular strength continued to increase from 24 to 48 weeks
      (p < 0.05). DISCUSSION: Resistance training appears to be an effective
      intervention for improving aspects of physical function and muscular strength;
      however, no significant changes in body composition were observed over the 48
      week intervention. CONCLUSION: Findings from the current investigation support
      use of resistance training for improving physical function among community
      dwelling older adults.

PMID- 29569115
TI  - [Systemic immune checkpoint inhibition : A promising treatment for urological
      tumors?]
AB  - Improved understanding of the immunomodulatory interactions between tumor cells
      and immune cells has led to new and promising systemic therapeutic approaches in
      the first- and second-line therapy of urological tumors. Particularly in the case
      of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors
      (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response
      rates of >20% that can be sustained over the long term. This review explains the
      approach of immunotherapy and summarizes the current phase III clinical situation
      on urothelial carcinoma and renal cell carcinoma. The current immunomodulatory
      therapeutic approaches for prostate cancer are discussed. Finally, we highlight
      new immunomodulatory therapeutic approaches in basic research.

PMID- 29569117
TI  - Twenty-year trends in cardiovascular risk among men and women in the United
      States.
AB  - BACKGROUND: Relative to men, women have experienced slower improvement in
      mortality in the US in recent decades. AIMS: We investigated 20-year trends in
      cardiovascular risk for men and women age 40 and over in the US to determine
      whether there was differential change in risk for men and women. METHODS: Using
      the National Health and Nutrition Examination Survey (NHANES), we estimated total
      cardiovascular risk, the prevalence of individual risk factors, and potential
      factors contributing to change in risk. RESULTS: Men showed steady reductions in
      cardiovascular risk over the 20 years; women experienced increased risk from 1990
      to 2000, but decreased risk from 2000 to 2010. Sex differences in cardiovascular
      risk changed so that there was no significant difference by sex at any age over
      50 in 2010. Large decreases in the prevalence of high risk lipids were important
      causes of reduction in risks for both sexes; changes in blood pressure were less
      important, except for women in the 2000-2010 period when they equaled the effect
      of changing lipids. Increasing medication usage and effectiveness drove
      improvements in blood pressure and total cholesterol for both sexes. In 2010
      there was no difference between men and women in the use of antihypertensives or
      cholesterol-lowering medications. Metabolic risk, as indexed by obesity and
      HbA1c, increased over time and went against the trend in the summary measure.
      Diabetes, smoking, and hormone therapy use did not explain changes in high blood
      pressure or high total cholesterol for either gender. CONCLUSIONS: Recent
      decreases in cardiovascular risk may lead to future reduction in cardiovascular
      events and mortality among both women and men.

PMID- 29569118
TI  - Arterial stiffness and left ventricular performance in elderly patients with
      persistent atrial fibrillation.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) and arterial stiffness
      (AS) increases with age. AIMS: To evaluate if AS is correlated to longitudinal
      strain (LS), a marker of left ventricular (LV) function, in elderly AF patients
      with preserved ejection fraction (EF) undergoing external cardioversion. METHODS:
      AS was measured using the cardio-ankle vascular index (CAVI), LS was calculated
      from echocardiographic data of three consecutive cardiac cycles. RESULTS: We
      enrolled 38 patients (age 76 +/- 8 years; men 60.5%; EF 65 +/- 7%). LS and CAVI
      were, respectively, - 17.7 +/- 3.7% and 9.7 +/- 1.3. Multivariate analysis showed
      that LV performance was inversely related to height (p < 0.001) and to the
      presence of AF-related symptoms (p = 0.008). LS grew with increasing values of
      CAVI (p = 0.038). CONCLUSIONS: In elderly AF patients with preserved systolic
      function, LV performance is directly associated with AS. This link could
      influence atrium remodeling and the incidence of arrhythmia relapse.

PMID- 29569119
TI  - More efficacious, equally safe: a meta-analysis comparing the safety of direct
      oral anticoagulants versus aspirin.

PMID- 29569121
TI  - Identifying Clinically Relevant Proteins for Targeted Analysis in the Development
      of a Multiplexed Proteomic Biomarker Assay.
AB  - In recent years, hundreds of candidate protein biomarkers have been identified
      using discovery-based proteomics. Despite the large number of candidate
      biomarkers, few proteins advance to clinical validation. Here, we describe a
      hypothesis driven approach to identify candidate biomarkers, previously
      characterized in the literature, with the highest probability of clinical
      applicability. A ranking method, the hypothesis directed biomarker ranking (HDBR)
      system, was developed to score candidate biomarkers based on seven criteria
      deemed important in the selection of clinically useful biomarkers. The HDBR
      system was initially applied to identify candidate biomarkers for the development
      of a diagnostic test for the early detection of colorectal cancer, but this
      system can be widely applied to identify biomarkers of relevance in different
      disease states, for diagnosis, prognostication, or any other specific purpose.

PMID- 29569120
TI  - Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate
      mofetil prophylaxis in the Japanese population.
AB  - Immune reconstitution affects clinical outcomes after allogeneic hematopoietic
      stem cell transplantation (HSCT), and it has been suggested that lymphocyte
      recovery affects survival after HSCT. However, few studies have examined
      lymphocyte recovery in Asian patients who received mycophenolate mofetil (MMF)
      prophylaxis for graft-versus-host disease. We retrospectively evaluated early
      lymphocyte recovery after HSCT among Japanese adults who received MMF
      prophylaxis. Patients were divided into two groups according to their median
      absolute lymphocyte count (ALC) on day 28 after HSCT as follows: the "low ALC
      group" (<= 0.22 * 109 cells/L) and the "high ALC group" (> 0.22 * 109 cells/L).
      With a median follow-up of 317 days, the high ALC group showed significantly
      better overall survival than the low ALC group (at 1 year: 62 vs. 46%, P = 0.02).
      The high ALC group also tended to have better non-relapse mortality than the low
      ALC group (at 1 year: 13 vs. 23%, P = 0.08). There was no significant difference
      in relapse rate between the high and low ALC groups (at 1 year: 29 vs. 35%, P =
      0.2). We conclude that among Japanese patients who received MMF prophylaxis, ALC
      on day 28 after HSCT was effective in predicting overall survival and non-relapse
      mortality.

PMID- 29569122
TI  - Impact of maternal thyroid autoantibodies positivity on the risk of early term
      birth: Ma'anshan Birth Cohort Study.
AB  - PURPOSE: We aim to investigate associations of maternal serum anti
      thyroperoxidase autoantibody (TPOAb) with duration of gestation. We aim to
      investigate whether maternal TPOAb positivity is associated with the risk of
      premature or early term birth. METHODS: This was a prospective birth cohort study
      performed in an iodine sufficient area of China. Serum samples were collected
      from 2931 women at both the first and second trimesters of pregnancy. Thyrotropin
      (TSH), free thyroxine (FT4), and TPOAb levels were measured. Data on gestational
      age at birth was obtained from delivery records. RESULTS: The prevalence of early
      term birth was 23.8%, while the prevalence of premature birth was 4.2%. The
      prevalence of TPOAb positivity was 12.1% in the first trimester and was 7.2% in
      the second trimester. Gestational age at birth was inversely associated with
      lgTPOAb both in the first trimester (beta, -0.283, 95% CI -0.408, -0.158; P <
      0.001) and in the second trimester (beta, -0.174, 95% CI -0.319, -0.030; P =
      0.018), after adjustment for potential confounding factors. There was a positive
      association of TPOAb positivity with the risk of early term birth both in the
      first (OR = 1.691, 95% CI 1.302, 2.197) and second trimesters (OR = 1.644, 95% CI
      1.193, 2.264), after adjustment for potential confounding factors. TPOAb
      positivity in the second trimester was associated with a 1.863-fold higher risk
      of premature birth (OR = 1.863, 95% CI 1.009, 3.441), after adjustment for
      potential confounding factors. CONCLUSIONS: Our results show that TPOAb is
      associated with shorter duration of gestation and with higher risk of premature
      and early term birth.

PMID- 29569123
TI  - Predictivity of clinical, laboratory and imaging findings in diagnostic
      definition of palpable thyroid nodules. A multicenter prospective study.
AB  - PURPOSE: To assess the role of clinical, biochemical, and morphological
      parameters, as added to cytology, for improving pre-surgical diagnosis of
      palpable thyroid nodules. METHODS: Patients with a palpable thyroid nodule were
      eligible if surgical intervention was indicated after a positive or suspicious
      for malignancy FNAC (TIR 4-5 according to the 2007 Italian SIAPEC-IAP
      classification), or two inconclusive FNAC at a >=3 months interval, or a negative
      FNAC associated with one or more risk factor. Reference standard was histological
      malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity,
      negative (NPV), and positive predictive value (PPV) were described. Multiple
      correspondence analysis (MCA) and logistic regression were applied. RESULTS:
      Cancer was found in 433/902 (48%) patients. Considering TIR4-5 only as positive
      cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV
      were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and
      NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%).
      Ultrasonographic size >=3 cm was independently associated with benignity among
      TIR2 cases (OR of malignancy 0.37, 95% CI 0.18-0.78). In TIR3 cases the hard
      consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84
      6.70, p < 0.001), while size alone, irrespective of consistency, was not
      diagnostically informative. No other significant association was found in TIR2
      and TIR3. CONCLUSIONS: The combination of cytology with clinical and
      ultrasonographic parameters may improve diagnostic definition of palpable thyroid
      nodules. However, the need for innovative diagnostic tools is still high.

PMID- 29569124
TI  - Optimizing Amikacin Dosage in Pediatrics Based on Population
      Pharmacokinetic/Pharmacodynamic Modeling.
AB  - OBJECTIVE: Our objective was to determine the population pharmacokinetic
      parameters of amikacin in pediatric patients to contribute to the future
      development of a revised optimum dose and population-specific dosing regimens.
      METHODS: We performed a retrospective chart review in non-critical pediatric
      patients (aged 1-12 years) who received amikacin for suspected or proven Gram
      negative infection at a university hospital. The population pharmacokinetic
      models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD)
      simulations were performed to explore the ability of different dosage regimens to
      achieve the pharmacodynamic targets. RESULTS: The analysis included 134 amikacin
      plasma concentrations from 67 patients with a mean +/- standard deviation age of
      4.1 +/- 3.9 years and bodyweight of 15 +/- 8.4 kg. The patients received an
      amikacin total daily dose (TDD) of 23 +/- 7.3 mg/kg, which resulted in peak and
      trough concentrations of 20.65 +/- 7.6 and 2.4 +/- 1.7 mg/l, respectively. The
      estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for
      total body clearance (CL) and the volume of distribution (V), respectively.
      Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of
      amikacin achieved the PK/PD target of peak serum concentration (Cpeak)/minimum
      inhibitory concentration (MIC) >= 8 for an MIC of 2 mg/l; higher doses were
      required to achieve higher MIC values. CONCLUSION: The simulation results
      indicated that amikacin 20 mg/kg once daily provided a higher probability of
      target attainment with lower toxicity than dosing three times daily. In addition,
      combination therapy is recommended for pathogens with an MIC of >= 8 mg/l.

PMID- 29569125
TI  - Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality
      Therapy in Esophageal Adenocarcinoma.
AB  - PURPOSE: To develop a nomogram that estimates 1-year recurrence-free survival
      (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the
      overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on
      the basis of 1-year recurrence risk. METHODS: In total, 568 consecutive patients
      with potentially resectable esophageal adenocarcinoma who underwent CRT were
      included for analysis, including 373 patients who underwent esophagectomy after
      CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality
      therapy). A nomogram for 1-year RFS was created using a Cox regression model. The
      upper tertile of the nomogram score was used to stratify patients in low-risk and
      high-risk groups for 1-year recurrence. The 5-year OS was compared between
      trimodality and bimodality therapy in low-risk and high-risk patients after
      propensity score matching, respectively. RESULTS: Median follow-up for the entire
      cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment
      groups was 56.3% (95% confidence interval [CI] 47.9-64.7) and 36.9% (95% CI 31.4
      42.4), respectively. The final nomogram for the prediction of 1-year RFS included
      male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3,
      and baseline SUVmax, with accurate calibration and reasonable discrimination (C
      statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in
      low-risk patients (p = 0.003), whereas it showed no significant survival benefit
      in high-risk patients (p = 0.302). CONCLUSIONS: The proposed nomogram estimates
      early recurrence risk. The addition of surgery to CRT provides a clear OS benefit
      in low-risk patients. The OS benefit of surgery in high-risk patients is less
      pronounced.

PMID- 29569127
TI  - Adjuvant Chemotherapy Versus Chemoradiotherapy Versus Surgery Alone for Early
      Gastric Cancer with One or Two Lymph Node Metastasis.
AB  - BACKGROUND: Limited studies exist comparing clinical outcomes by adjuvant
      treatment for pT1N1 gastric cancer. This study compared the disease-free survival
      (DFS) of patients with pT1N1 gastric cancer according to the type of adjuvant
      treatment-surgery alone, chemotherapy (CTx), and chemoradiotherapy (CCRTx)-and
      evaluated risk factors for tumor recurrence. METHODS: Between 1995 and 2015, 738
      patients underwent radical gastrectomy for pT1N1 gastric cancer and were divided
      into three groups: surgery alone (n = 355), CTx (n = 214), and CCRTx (n = 169).
      Chronological changes in adjuvant treatment type and chemotherapeutic regimens
      were evaluated and DFS was compared. Risk factors for tumor recurrence were
      analyzed. RESULTS: The proportion of patients who underwent surgery alone was
      more than 50% until 2001, and the proportion of those who had either CTx or CCRTx
      was more than 50% from 2002 to 2011, after which the proportion who underwent
      surgery alone increased again. The main chemotherapeutic agent was 5-fluorouracil
      with leucovorin. The 5-year DFS was 96.5% in the surgery-alone group, 96.0% in
      the CTx group, and 95.8% in the CCRTx group (no significant difference). The
      various chemotherapeutic regimens did not show differences in DFS. In univariate
      and multivariate analyses, adjuvant CTx and CCRTx showed no beneficial effect
      with regard to tumor recurrence. CONCLUSIONS: Because adjuvant CTx and CCRTx did
      not show any benefit with regard to tumor recurrence, these treatment strategies
      might be unnecessary for pT1N1 gastric cancer after gastrectomy. Further studies
      are necessary to reveal pT1N1 gastric cancer patient subgroups who might benefit
      from adjuvant treatments.

PMID- 29569126
TI  - Palliative Care is Associated with Reduced Aggressive End-of-Life Care in
      Patients with Gastrointestinal Cancer.
AB  - BACKGROUND: We examined the delivery of physician palliative care (PC) services
      and its association with aggressive end-of-life care (EOLC) in patients with
      gastrointestinal (GI) cancer in Ontario, Canada. METHODS: All patients with
      primary cause of death from esophageal, gastric, colon, and anorectal cancer from
      January 2003 to December 2013 were identified. PC services within 2 years of
      death were classified: (1) any PC; (2) timing of first PC (<= 7, 8-90, 91-180,
      and 181-730 days before death); and (3) intensity of PC measured by number of
      days used (1st-25th, 26th-50th, 51st-75th, and 76th-100th percentiles).
      Aggressive EOLC was defined as any of the following: chemotherapy, emergency
      department visits, hospital or intensive care unit (ICU) admissions (all <= 30
      days of death), and death in hospital and in the ICU; these were combined as a
      composite outcome (any aggressive EOLC). RESULTS: The cohort included 34,630
      patients, of whom 74% had at least one PC service. Timing of the first PC service
      varied: <= 7 (12%), 8-90 (42%), 91-180 (16%), and 181-730 (30%) days before
      death. Compared with patients not receiving PC, any PC was associated with a
      reduction in any aggressive EOLC (risk ratio [RR] 0.75, 95% confidence interval
      [CI] 0.74-0.76); this association was similar regardless of timing of the first
      PC service. The most dramatic reduction in aggressive EOLC occurred in patients
      who received the greatest number of days of PC (RR 0.65, 95% CI 0.63-0.67).
      CONCLUSIONS: The majority of patients received PC within 2 years of death. A
      larger number of days of PC was associated with a greater reduction in aggressive
      EOLC.

PMID- 29569128
TI  - Letter to the Editor.

PMID- 29569129
TI  - Cytokine Responses in Severe Traumatic Brain Injury: Where There Is Smoke, Is
      There Fire?
AB  - This scoping review will discuss the basic functions and prognostic significance
      of the commonly researched cytokines implicated in severe traumatic brain injury
      (sTBI), including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL
      1beta), IL-6, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1),
      transforming growth factor-beta (TGF-beta), substance P, and soluble CD40 ligand
      (sCD40L). A scoping review was undertaken with an electronic search for articles
      from the Ovid MEDLINE, PUBMED and EMBASE databases from 1995 to 2017. Inclusion
      criteria were original research articles, and reviews including both animal
      models and human clinical studies of acute (< 3 months) sTBI. Selected articles
      included both isolated sTBI and sTBI with systemic injury. After applying the
      inclusion criteria and removing duplicates, 141 full-text articles, 126 original
      research articles and 15 review articles, were evaluated in compiling this review
      paper. A single reviewer, CC, completed the review in two phases. During the
      first phase, titles and abstracts of selected articles were reviewed for
      inclusion. A second evaluation was then conducted on the full text of all
      selected articles to ensure relevancy. From our current understanding of the
      literature, it is unlikely a single biomarker will be sufficient in accurately
      prognosticating patients with sTBI. Intuitively, a more severe injury will
      demonstrate higher levels of inflammatory cytokines which may correlate as a
      marker of severe injury. This does not mean, necessarily, these cytokines have a
      direct and causal role in the poor outcome of the patient. Further research is
      required to better delineate the complex systemic inflammatory and CNS
      interactions that occur during sTBI before they can be applied as a reliable
      prognostic tool.

PMID- 29569130
TI  - Correlation of Noninvasive Blood Pressure and Invasive Intra-arterial Blood
      Pressure in Patients Treated with Vasoactive Medications in a Neurocritical Care
      Unit.
AB  - BACKGROUND: The correlation between noninvasive (oscillometric) blood pressure
      (NBP) and intra-arterial blood pressure (IAP) in critically ill patients
      receiving vasoactive medications in a Neurocritical Care Unit has not been
      systematically studied. The purpose of this study is to examine the relationship
      between simultaneously measured NBP and IAP recordings in these patients.
      METHODS: Prospective observational study of patients (N = 70) admitted to a
      neurocritical care unit receiving continuous vasopressor or antihypertensive
      infusions. Paired NBP/IAP observations along with covariate and demographic data
      were abstracted via chart audit. Analysis was performed using SAS v9.4. RESULTS:
      A total of 2177 paired NBP/IAP observations from 70 subjects (49% male, 63%
      white, mean age 59 years) receiving vasopressors (n = 21) or antihypertensive
      agents (n = 49) were collected. Paired t test analysis showed significant
      differences between NBP versus IAP readings: ([systolic blood pressure (SBP):
      mean = 136 vs. 140 mmHg; p < 0.0001], [diastolic blood pressure (DBP): mean = 70
      vs. 68 mmHg, p < 0.0001], [mean arterial blood pressure (MAP): mean = 86 vs. 90
      mmHg, p < 0.0001]). Bland-Altman plots for MAP, SBP, and DBP demonstrate good
      inter-method agreement between paired measures (excluding outliers) and
      demonstrate NBP-IAP SBP differences at extremes of blood pressures. Pearson
      correlation coefficients show strong positive correlations for paired MAP (r =
      0.82), SBP (r = 0.84), and DBP (r = 0.73) recordings. An absolute NBP-IAP SBP
      difference of > 20 mmHg was seen in ~ 20% of observations of nicardipine, ~ 25%
      of observations of norepinephrine, and ~ 35% of observations of phenylephrine.
      For MAP, the corresponding numbers were ~ 10, 15, and 25% for nicardipine,
      norepinephrine, and phenylephrine, respectively. CONCLUSION: Despite overall
      strong positive correlations between paired NBP and IAP readings of MAP and SBP,
      clinically relevant differences in blood pressure are frequent. When treating
      with vasoactive infusions targeted to a specific BP goal, it is important to keep
      in mind that NBP and IAP values are not interchangeable.

PMID- 29569131
TI  - Acquired spondylolysis and spinopelvic sagittal alignment.
AB  - Acquired spondylolysis represents an uncommon complication of spine surgery, of
      an unknown incidence and etiology. We studied patients presenting this rare
      entity, with the purpose to investigate the incidence, imaging findings,
      patients' clinical characteristics, as well as to provide an interpretation of
      the mechanisms that may lead to this phenomenon. The presented working
      hypothesis, regarding etiology, suggests that there is a relation between
      variations in spinopelvic sagittal alignment and acquired spondylolysis. Between
      January 2010 and January 2015, six patients presented spondylolysis after short
      segment transforaminal lumbar interbody fusion, at a mean time of 43 months after
      surgery. The preoperative intactness and postoperative defect of pars
      interarticularis were documented with computed tomography scans in all patients.
      Standard radiographical spinopelvic parameters were measured before and after
      surgery. The optimum values of lumbar lordosis (LL) and pelvic incidence minus
      lumbar lordosis modifier (PI-LL mismatch) were calculated as well. The incidence
      of acquired spondylolysis was 0.95% among patients with short-segment lumbar
      fusion. Patients presented high-grade PI with a vertically orientated sacral
      endplate, while LL was found 9 degrees  greater and PI-LL mismatch 9 degrees 
      lower than the respective optimum values, indicating a non-harmonized alignment.
      In conclusion, acquired spondylolysis, though rare, may occur in patients with
      high-grade PI and sacral slope, and suboptimal spinopelvic sagittal alignment
      after lumbar spine surgery, thereby highlighting the importance of detailed
      preoperative planning in spine surgery, along with the study of sagittal balance.

PMID- 29569133
TI  - Author Correction: Listening to the Patient Perspective: Psychiatric Inpatients'
      Attitudes Towards Physical Restraint.
AB  - The original version of this article unfortunately contained a mistake in the
      author group section. The correct name of the second author is "Saed Maree" and
      the third author is "Aviv Segev."

PMID- 29569132
TI  - Fixation method for treatment of unstable distal clavicle fracture: systematic
      review and network meta-analysis.
AB  - Surgical management is recommended for unstable distal clavicle fractures. A
      variety of methods have been previously reported, but there is no current
      consensus regarding which method is most suitable. Therefore, we have conducted a
      systematic review and network meta-analysis to compare postoperative shoulder
      function and complications between different fixation methods to identify which
      class of fixation is best for unstable distal clavicle fractures. We searched the
      literature systematically using eligibility criteria of all comparative studies
      that compared postoperative outcomes of coracoclavicular fixation (tight rope,
      screw or endobutton), hook plating, plate and screws, tension band wiring and
      transacromial pinning fixation for unstable distal clavicle fractures from
      PubMed, EMBASE, and Scopus databases up to February 10, 2018. Two reviewers
      independently extracted data. A network meta-analysis was applied to combine
      direct and indirect evidence and to estimate the relative effects of the
      treatment options. The probability of being the best treatment was estimated
      using surface under the cumulative ranking curves (SUCRA). Ten comparative
      studies (n = 505 patients) with one RCT study (n = 42) met the inclusion
      criteria. Intervention included coracoclavicular fixation (n = 111 patients),
      hook plating (n = 300 patients), plate and screws (n = 41 patients), tension band
      wiring (n = 81 patients) and transacromial pinning (n = 14 patients). A network
      meta-analysis showed that CM scores of coracoclavicular fixation were
      significantly higher when compared to hook plate and tension band wiring, with
      pooled mean of 2.98 (95% CI 0.05-5.91) and 7.11 (95% CI 3.04-11.18). For UCLA, CC
      fixation and plate and screw fixation had significantly higher scores compared to
      hook plating fixation with a mean score 2.22 (95% CI 0.44-3.99) and 3.20 (95% CI
      0.28-6.12), respectively. In terms of complications, plate and screw fixation had
      lower risk with RRs of 0.63 (95% CI 0.20-1.98), 0.37 (95% CI 0.19-0.72), 0.11
      (95% CI 0.04-0.30) and 0.02 (95% CI 0.002-0.16) when compared to coracoclavicular
      fixation, hook plating, tension band wiring and transacromial pinning. The SUCRA
      probabilities of CC fixation were in the first rank with 96.8% for CMS, while
      plate and screw fixation were in the first rank with 67.7 and 93.8% for UCLA
      score and complications. We recommend using plate and screw and CC fixation as
      the first- and second-line treatment of unstable distal clavicle fractures. As
      the quality of studies for this meta-analysis was not high, larger and higher
      quality randomized controlled trials are required to confirm these conclusions
      for informed clinical decision making.

PMID- 29569134
TI  - The microbiology of chronic rhinosinusitis with and without nasal polyps.
AB  - OBJECTIVE: To compare the microbiological features in middle meatus samples from
      chronic rhinosinusitis (CRS) patients with nasal polyps (CRSwNP) and those
      without nasal polyps (CRSsNP), and control subjects. METHODS: A total of 136
      CRSwNP patients, 66 CRSsNP patients, and 49 control subjects who underwent
      endoscopic surgery in Beijing TongRen Hospital were enrolled between January 2014
      and January 2016. Swab samples were obtained from the middle meatus during
      surgery and processed for the presence of aerobic and non-aerobic bacteria and
      fungi. Information on the allergic rhinitis, asthma, the percentage of
      eosinophils in peripheral blood, and the history of smoking and surgery was
      collected. RESULTS: The overall isolation rate for bacteria was 81.3% for the
      three groups, with the lowest in the CRSsNP group (77.3%) and the highest in the
      CRSwNP group (88.4%). There were no significant differences in isolation rates
      among the three groups (P = 0.349). The three most common bacterial species were:
      Coagulase-negative Staphylococcus (24.3%), Corynebacterium (19.9%), and
      Staphylococcus epidermidis (19.1%) in the CRSwNP group; S. epidermidis (21.2%),
      Corynebacterium (21.2%), Coagulase-negative staphylococcus (18.2%), and
      Staphylococcus aureus (13.6%) in the CRSsNP group; S. epidermidis (30.6%),
      Coagulase-negative Staphylococcus (28.6%), and S. aureus (14.3%) in the control
      group. For the bacterial species with high isolation rates, no significant
      difference in the microbial cultures was observed among the three groups; whereas
      in the CRSwNP group, a relatively high proportion of Citrobacter (5.9%, a
      bacterium with low isolation rate) was observed compared with the CRSsNP and
      control groups (all 0.0%). Furthermore, when samples were categorized into
      subgroups according to the percentage of eosinophils, some bacterial species
      showed different rates in the CRSwNP group (e.g., S. aureus, 3.3% in the subgroup
      with normal percentage of eosinophils, 17.2% in the subgroup with increased
      percentage of eosinophils, P = 0.011). CONCLUSIONS: There were no significant
      differences in the microbiological features (except Citrobacter) in middle meatus
      samples from CRSwNP patients, CRSsNP patients, and control subjects. S. aureus
      may promote eosinophilic inflammatory response, while S. epidermidis may promote
      non-eosinophilic inflammatory response.

PMID- 29569135
TI  - Malnutrition and refeeding syndrome prevention in head and neck cancer patients:
      from theory to clinical application.
AB  - PURPOSE: The goal of this review is to raise awareness about refeeding syndrome
      (RFS) and to give a comprehensive presentation of recent guidelines and latest
      scientific data about nutritional management among head and neck cancer (HNC)
      patients while focusing on RFS prevention. METHODS: A review of literature for
      nutritional assessment and RFS management was conducted. Electronic searches of
      Medline, Cochrane, PubMed and Embase databases for articles published in peer
      reviewed journals were conducted from February to September 2017 using the
      keywords: "nutrition assessment", "head and neck cancer", "refeeding syndrome"
      and "guidelines". Articles, reviews, book references as well as national and
      international guidelines in English and French were included. RESULTS: The
      prevalence of malnutrition is high in HNC patients and a large number of them
      will need artificial nutritional support or refeeding intervention. RFS is
      characterized by fluid and electrolyte imbalance associated with clinical
      manifestations induced by rapid refeeding after a period of malnutrition or
      starvation. Regarding risk factors for malnutrition and RFS, HNC patients are
      particularly vulnerable. However, RFS remains unrecognized among head and neck
      surgeons and medical teams. Practical data are summarized to help organizing
      nutritional assessment and refeeding interventions. It also summarizes preventive
      measures to reduce RFS incidence and morbidity in HNC population. CONCLUSION:
      Nutritional assessment and early refeeding interventions are crucial for HNC
      patients care. As prevention is the key for RFS management, early identification
      of patients with high risks is crucial and successful nutritional management
      requires a multidisciplinary approach.

PMID- 29569136
TI  - How to clarify the aims of empathy in medicine.
AB  - This paper argues that enthusiasm for empathy has grown to the point at which
      empathy has taken on the status of an "ideal" in modern medicine. We need to
      pause and scrutinize this ideal before moving forward with empathy training
      programs for medical students. Taking empathy as an ideal obscures the
      distinction between the multiple aims that calls for empathy seek to achieve.
      While these aims may work together, they also come apart and yield different
      recommendations about the sort of behavior physicians should cultivate in a given
      situation. I begin by demonstrating how enthusiasm for empathy has increased
      dramatically. I then specify precisely what I mean in calling empathy an "ideal."
      I then describe some dangers associated with taking empathy to be an ideal
      unreflectively. I discuss the merits of works that provide conceptualizations of
      empathy that are specifically tailored for the medical domain and conclude that
      although these works move discussions about empathy in medical care forward, they
      could do more to foreground the goals and aims underlying calls for increased
      empathy. I provide specific suggestions as to how exactly we might foreground
      these goals and aims to further avoid conceptual confusion about empathy in
      medical education.

PMID- 29569137
TI  - Correction to: Point shear wave ultrasound elastography with Esaote compared to
      real-time 2D shear wave elastography with supersonic imagine for the
      quantification of liver stiffness.
AB  - Unfortunately, in the first sentence under the section head "Point shear wave
      elastography", the transducer name was misspelled as CA541 (rather than CA451).

PMID- 29569138
TI  - Tumour endoprosthesis replacement in the proximal tibia after intra-articular
      knee resection in patients with sarcoma and recurrent giant cell tumour.
AB  - PURPOSE: Proximal tibia replacements are commonly associated with post-operative
      complications and poor functional results due to an insufficiency of the extensor
      mechanism. METHODS: This study evaluated the clinical results with a special
      emphasis of the extensor mechanism reconstruction with a reattachment tube and
      complications after intra-articular resection of the proximal tibia and
      reconstruction with a tumour endoprosthesis (MUTARS(r)) in 98 patients (median
      age 18 years) with malignant bone tumours or giant cell tumours. RESULTS: Kaplan
      Meier analysis showed that the limb survival rates were 94.9, 90.5 and 74.5% at
      one, two and ten years, respectively. Periprosthetic infection was the most
      common reason for secondary amputation (eight patients). The cumulative incidence
      rates of prosthetic failure (Henderson II-IV) were 18% at two years and 29% at
      five years post-operatively. An active extension deficit of more than 10 degrees 
      was noted in six patients only. CONCLUSIONS: These results suggest that limb
      salvage with tumour prostheses after intra-articular resection can achieve good
      functional results with an active extension of the knee in the majority of
      patients. While mechanical complications can be treated successfully with
      revision surgery, periprosthetic infection continues to be the main reason for
      secondary amputation.

PMID- 29569139
TI  - Bone-preserving total hip arthroplasty in avascular necrosis of the hip-a matched
      pairs analysis.
AB  - PURPOSE: Short-stem hip arthroplasty has the potential advantage of femoral bone
      stock preservation, especially in view of the expected revisions in the often
      relatively young patients. Despite short-stem hip prosthesis are increasingly
      used for total hip arthroplasty, there are no sufficient mid- and long-term
      results especially for patients with avascular femoral head osteonecrosis. The
      present study investigates mid-term functional results as well as the revision
      rate following implantation of a short-stem prosthesis. METHODS: In the period
      06/2005 until 12/2013, a total of 351 short-stem hip prostheses were implanted.
      The study included 331 complete data sets. A retrospective analysis was performed
      using the Oxford Hip Score. All revisions were registered. RESULTS: In a total of
      331 prostheses, the Oxford Hip Score was "excellent" in 66.2%, "good" in 12.7%,
      "fair" in 13.0%, and "poor" in 8.2% with a mean follow-up of 57.4 months (SD +/-
      29.8; range 24-115). In 26 cases, aseptic osteonecrosis of the hip was the
      indication (7.9%). The Oxford Hip Score was "excellent" in 66.7%, "good" in 0.0%,
      "fair" in 20.8%, and "poor" in 12.5%. The cumulated five year survival rate was
      96.7%. CONCLUSION: In mid-term observation, the Metha(r) short-stem prosthesis
      shows no disadvantage in functional outcome and in survival time compared to a
      standard hip stem. Providing a correct indication, the Metha(r) short stem is a
      valuable option in total hip arthroplasty for younger patients with avascular
      osteonecrosis of the femoral head. Evaluation has shown no significant
      differences between aseptic osteonecrosis and other indications.

PMID- 29569140
TI  - Mobile-bearing unicompartmental knee arthroplasty in old-aged patients
      demonstrates superior short-term clinical outcomes to open-wedge high tibial
      osteotomy in middle-aged patients with advanced isolated medial osteoarthritis.
AB  - PURPOSE: The aim of the present study was to compare the clinical outcomes of
      mobile-bearing unicompartmental knee arthroplasty (MB-UKA) and open-wedge high
      tibial osteotomy (OWHTO) for advanced isolated medial osteoarthritis (OA).
      METHODS: Patients with advanced medial compartment OA (Ahlback grade >= II) who
      underwent either MB-UKA with Oxford Knee or OWHTO were included. The minimum
      follow-up was two years. Clinical outcomes were evaluated using the Hospital for
      Special Surgery (HSS) score, knee score (KS), and function score (FS) of the Knee
      Society Knee Scoring System. Pre-operative and post-operative values were
      compared within groups. Pre-operative and post-operative values and the degree of
      change were compared between the two groups. Radiologic progression of OA in
      either the lateral or patellofemoral compartment was evaluated. RESULTS: Forty
      knees (20 received MB-UKA, 20 received OWHTO) were enrolled. The mean age was
      higher in the MB-UKA group (67.9 +/- 9.0 years) than in the OWHTO group (58.4 +/-
      5.5 years). The HSS score, KS, and FS were significantly increased post
      operatively in both groups. The preoperative HSS score, KS, and FS were
      significantly lower in the MB-UKA than in the OWHTO group; however, only the post
      operative HSS score was significantly higher in the MB-UKA group. The changes in
      HSS score and KS were also greater in the MB-UKA group. There was no significant
      difference in OA progression. CONCLUSIONS: Although there was an age difference
      between the two groups, MB-UKA demonstrated superior short-term clinical outcomes
      to OWHTO for advanced isolated medial OA. In particular, MB-UKA was more
      effective in terms of pain relief.

PMID- 29569141
TI  - A simple and widely available alternative method for endotracheal tube cuff
      pressure monitoring.

PMID- 29569142
TI  - Sample size calculations for randomized clinical trials published in
      anesthesiology journals: a comparison of 2010 versus 2016.
AB  - PURPOSE: Although every randomized clinical trial (RCT) needs participants,
      determining the ideal number of participants that balances limited resources and
      the ability to detect a real effect is difficult. Focussing on two-arm, parallel
      group, superiority RCTs published in six general anesthesiology journals, the
      objective of this study was to compare the quality of sample size calculations
      for RCTs published in 2010 vs 2016. METHODS: Each RCT's full text was searched
      for the presence of a sample size calculation, and the assumptions made by the
      investigators were compared with the actual values observed in the results.
      Analyses were only performed for sample size calculations that were amenable to
      replication, defined as using a clearly identified outcome that was continuous or
      binary in a standard sample size calculation procedure. RESULTS: The percentage
      of RCTs reporting all sample size calculation assumptions increased from 51% in
      2010 to 84% in 2016. The difference between the values observed in the study and
      the expected values used for the sample size calculation for most RCTs was
      usually > 10% of the expected value, with negligible improvement from 2010 to
      2016. CONCLUSION: While the reporting of sample size calculations improved from
      2010 to 2016, the expected values in these sample size calculations often assumed
      effect sizes larger than those actually observed in the study. Since overly
      optimistic assumptions may systematically lead to underpowered RCTs, improvements
      in how to calculate and report sample sizes in anesthesiology research are
      needed.

PMID- 29569143
TI  - A Framework for Culturally Relevant Online Learning: Lessons from Alaska's Tribal
      Health Workers.
AB  - Culturally relevant health promotion is an opportunity to reduce health
      inequities in diseases with modifiable risks, such as cancer. Alaska Native
      people bear a disproportionate cancer burden, and Alaska's rural tribal health
      workers consequently requested cancer education accessible online. In response,
      the Alaska Native Tribal Health Consortium cancer education team sought to create
      a framework for culturally relevant online learning to inform the creation of
      distance-delivered cancer education. Guided by the principles of community-based
      participatory action research and grounded in empowerment theory, the project
      team conducted a focus group with 10 Alaska Native education experts, 12
      culturally diverse key informant interviews, a key stakeholder survey of 62
      Alaska Native tribal health workers and their instructors/supervisors, and a
      literature review on distance-delivered education with Alaska Native or American
      Indian people. Qualitative findings were analyzed in Atlas.ti, with common themes
      presented in this article as a framework for culturally relevant online
      education. This proposed framework includes four principles: collaborative
      development, interactive content delivery, contextualizing learning, and creating
      connection. As an Alaskan tribal health worker shared "we're all in this
      together. All about conversations, relationships. Always learn from you/with you,
      together what we know and understand from the center of our experience, our ways
      of knowing, being, caring." The proposed framework has been applied to support
      cancer education and promote cancer control with Alaska Native people and has
      motivated health behavior change to reduce cancer risk. This framework may be
      adaptable to other populations to guide effective and culturally relevant online
      interventions.

PMID- 29569144
TI  - A Highly Pathogenic Strain of Porcine Deltacoronavirus Caused Watery Diarrhea in
      Newborn Piglets.
AB  - Porcine deltacoronavirus (PDCoV) is a newly identified virus that causes watery
      diarrhea in newborn piglets and results in significant economic losses to the pig
      industry. Since first reported in Hong Kong in 2012, PDCoV has been subsequently
      detected in USA, South Korea, Thailand, and mainland China. Here we isolated a
      strain of PDCoV, named CHN-GD-2016, from the intestinal content of a diseased
      newborn piglet with severe diarrhea in a pig farm in Guangdong, China. PDCoV CHN
      GD-2016 could be identified by immunofluorescence with PDCoV specific rabbit
      antisera, and typical crown-shaped particles with spiky surface projections of
      this PDCoV were observed with electron microscopy. Genomic analysis showed that
      the PDCoV CHN-GD-2016 was closely related to other Chinese PDCoV strains, with
      the highest sequence similarity with the strain CHN/Tianjin/2016. Importantly,
      inoculation of newborn piglets with 1 * 105 TCID50 of CHN-GD-2016 by oral feeding
      successfully reproduced clear clinical symptoms, including vomiting, dehydration,
      and severe diarrhea in piglets. In addition, the virus RNA in rectal swabs from 1
      to 7 days post inoculation was detected, macroscopic and microscopic lesions in
      small intestine were observed, and viral antigen was also detected in the small
      intestines with immunohistochemical staining. Collectively, the data show in this
      study confirms that PDCoV is present in Guangdong, China and is highly pathogenic
      in newborn piglets.

PMID- 29569145
TI  - First Serological Evidence on Endemicity of HEV Infection in Wild Boar (Sus
      scrofa) Populations from Portugal.

PMID- 29569146
TI  - Anticoagulation in atrial fibrillation with heart failure.
AB  - Heart failure (HF) and atrial fibrillation (AF) frequently coexist, and they can
      beget one another due to similar factors and shared pathophysiology. These
      pathophysiologic changes promote the episodes of AF, while they in turn
      predispose to the exacerbation of HF. In this review, we will discuss
      pathophysiological mechanisms shared by AF and HF. Patients with concomitant HF
      and AF are at a particularly high risk of thromboembolism, which contribute to
      even worse symptoms and poorer prognosis. Vitamin K antagonists (VKA) (warfarin)
      were the traditional medication in AF patients for the prevention of stroke,
      whereas the advance of novel non-VKA oral anticoagulants (NOACs) (dabigatran,
      apixaban, rivaroxaban, and edoxaban) is challenging these standard prescriptions.
      NOACs' potential advantages over warfarin, including fixed dosing regimens, wide
      therapeutic window, and more sustained anticoagulant response, promote clinicians
      to consider these novel agents in the first place. However, some data suggested
      patients with AF and HF may receive different therapeutic response than those
      with AF alone in anticoagulant treatment. Accordingly, we aim to assess the
      potential role of oral anticoagulants, especially NOACs, in the management of
      patients with concomitant AF and HF.

PMID- 29569147
TI  - Hypertension and its severity in children with steroid sensitive nephrotic
      syndrome during remission.
AB  - BACKGROUND AND OBJECTIVE: Hypertension is not a typical feature of steroid
      sensitive nephrotic syndrome (SSNS) and the presence of persistent hypertension
      is suggestive of significant renal lesion. There is paucity of data regarding
      occurrence and severity of hypertension in SSNS in pediatric population during
      remission and was the main objective of this study. In addition, correlation with
      factors like family history, BMI, and lipid profile was studied. METHODS: Cross
      sectional study conducted at tertiary care center in India including 81 children
      of infrequent relapsing SSNS between 1 and 10 years in remission and was off
      steroids. Grading and severity of hypertension were assessed. Statistical
      analysis was done using SPSS version 21.0. RESULTS: Median age of presentation
      was 5 years, with male:female ratio of 1.3:1. Out of 81 infrequent relapsing SSNS
      children, 23.45% (19) had hypertension. Among those children with hypertension (n
      = 19), 73.68% (14) had positive family history compared to 32.25% (20) in those
      without hypertension. Positive correlation was found between BP and serum
      cholesterol and LDL. Of the hypertensive patients, 1 (5.26%) had fundus changes,
      2 (10.52%) had features of left ventricular hypertrophy, and 13 (68.42%) had non
      nephrotic range proteinuria. CONCLUSION: There is high incidence of hypertension
      in NS children during remission. Though significant positive correlation was
      found with positive family history of hypertension and deranged lipid profile
      highlighting possibility of essential hypertension in them, there is need for
      close active monitoring and management of hypertension in them as untreated cases
      may have significant target organ damage.

PMID- 29569148
TI  - [Lipid-lowering therapy in the elderly : Who profits from which target values?]
AB  - Lowering low-density lipoprotein (LDL) cholesterol levels has been proven to
      reduce the incidence of cardiovascular and cerebrovascular events and mortality.
      So far recommendations have not provided information as to a meaningful duration
      of cholesterol-lowering therapy and were largely guided by economic constraints
      and limited therapeutic options. In light of the decline in the price of statins,
      the essential therapeutic agent and the increased efficacy of therapeutic
      options, treatment can nowadays be geared to target values that can be expected
      to have an optimal effect even in old age. The most favorable level of LDL
      cholesterol for primary prevention is around and below 100 mg/dl, provided
      continuous adherence to these low levels from adolescence onwards. With later
      onset of cholesterol reduction the existence of initial atheromatous deposits
      must be expected. Therefore, with age and the manifestation of other risk factors
      the optimal treatment targets increasingly converge to those for which experience
      has been gained from secondary prevention. Both measurements of the effect of
      cholesterol lowering on the volume of atheromatous plaques and of the incidence
      of vascular events indicate a target for LDL-cholesterol well below 70 mg/dl and
      in the range 50-60 mg/dl. At the onset of cholesterol lowering in advanced age, a
      smaller effect has to be expected but due to the increasing incidence rate of
      vascular events a higher number of events may be avoided; thus, the efficiency
      does not necessarily decrease; however, long-term studies indicate that earlier
      cholesterol lowering provides an advantage for more than a decade, in terms of
      preventing vascular disease, which tends to increase. Therefore, optimal
      cardiovascular prevention involves moderate measures to maintain the LDL
      cholesterol below 100 mg/dl lifelong from childhood on.

PMID- 29569149
TI  - [Aortic diseases : Modern diagnostic and therapeutic strategies].
AB  - Aortic diseases include not only the thoracic but also the abdominal part of the
      aorta. In the etiology cardiovascular risk factors, such as hypertension, smoking
      and hyperlipoproteinemia play a major role, but more and more genetic diseases
      with familiar predisposition are being identified. Even large aneurysms remain
      asymptomatic as long as other organs in the neighborhood are not damaged and no
      acute aortic event occurs including aortic dissection, intramural hematoma,
      penetrating aortic ulcer, and traumatic aortic injury. Standardized algorithms
      allow precise and rapid diagnosis for initiating medicinal therapy or operative
      and/or endovascular interventions (thoracic/endovascular aortic repair,
      TEVAR/EVAR) in this emergency situation. Specialized aortic centers are
      recommended to form localized regional networks.

PMID- 29569150
TI  - Impaired lipid metabolism markers to assess the risk of neuroinflammation in
      autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a multifactorial disorder caused by an
      interaction between environmental risk factors and a genetic background. It is
      characterized by impairment in communication, social interaction, repetitive
      behavior, and sensory processing. The etiology of ASD is still not fully
      understood, and the role of neuroinflammation in autism behaviors needs to be
      further investigated. The aim of the present study was to test the possible
      association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal
      prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and
      nuclear kappa B (NF-kappaB) and the severity of cognitive disorders, social
      impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and
      NF-kappaB as biochemical parameters related to neuroinflammation were determined
      in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate
      and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social
      Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46
      neurotypical controls. The data indicated that ASD patients have remarkably
      higher levels of the measured parameters compared to neurotypical controls,
      except for EP2 receptors that showed an opposite trend. While the measured
      parameter did not correlate with the severity of social and cognitive
      dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the
      dysfunction in sensory processing. NF-kappaB was significantly increased in
      relation to age. Based on the discussed data, the positive correlation between
      PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation
      in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as
      biomarkers of autism severity. NF-kappaB as inflammatory inducer showed an
      elevated level in plasma of ASD individuals. Receiver operating characteristic
      analysis together with predictiveness diagrams proved that the measured
      parameters could be used as predictive biomarkers of biochemical correlates to
      ASD.

PMID- 29569151
TI  - Mass scaling of the resting and maximum metabolic rates of the black carp.
AB  - We investigated the body mass (M) scaling of resting metabolic rate (RMR),
      maximum metabolic rate (MMR), excess post-exercise oxygen consumption (EPOC),
      blood parameters, and organ masses of black carp (Mylopharyngoden piceus). The
      results showed that RMR scaled with M of the fish by an exponent (b) of 0.833
      (bR), which was significantly larger than 0.75. MMR scaled with M by a power of
      0.775 (bM), which was significantly lower than 1 and may be due to a small size
      proportion of red muscle. No difference between bR and bM or correlation between
      factorial aerobic scope and M was found. However, EPOC scaled positively with M
      by a power of 1.231, suggesting a constant aerobic capacity and an enhanced
      anaerobic capacity with fish growth. Mass of the inactive organs scaled with M by
      a power of 1.005, which was significantly larger than 1 and was negatively
      correlated with RMR, suggesting that the proportion of inactive organs increases
      with fish growth, which may contribute to the negative scaling of RMR. Red blood
      cell surface area (S) did not increase with increasing M, suggesting that the
      ontogenetic decrease in the surface area to volume ratio of cells may not
      contribute to the negative scaling of RMR. The predicted bR value (0.846) by the
      average S (1.746 um2) differs by only 1.62% from the observed bR value using our
      previously reported S - bR function in carp, suggesting that the species-specific
      cell size, rather than its ontogenetic change, affects the metabolic scaling of a
      species.

PMID- 29569152
TI  - Predicting mortality and incident immobility in older Belgian men by
      characteristics related to sarcopenia and frailty.
AB  - : There is an increasing awareness of sarcopenia in older people. We applied
      machine learning principles to predict mortality and incident immobility in older
      Belgian men through sarcopenia and frailty characteristics. Mortality could be
      predicted with good accuracy. Serum 25-hydroxyvitamin D and bone mineral density
      scores were the most important predictors. INTRODUCTION: Machine learning
      principles were used to predict 5-year mortality and 3-year incident severe
      immobility in a population of older men by frailty and sarcopenia
      characteristics. METHODS: Using prospective data from 1997 on 264 older Belgian
      men (n = 152 predictors), 29 statistical models were developed and tuned on 75%
      of data points then validated on the remaining 25%. The model with the highest
      test area under the curve (AUC) was chosen as the best. From these, ranked
      predictor importance was extracted. RESULTS: Five-year mortality could be
      predicted with good accuracy (test AUC of .85 [.73; .97], sensitivity 78%,
      specificity 89% at a probability cut-off of 22.3%) using a Bayesian generalized
      linear model. Three-year incident severe immobility could be predicted with fair
      accuracy (test AUC .74 [.57; .91], sensitivity 67%, specificity 78% at a
      probability cut-off of 14.2%) using a multivariate adaptive regression splines
      model. Serum 25-hydroxyvitamin D levels and hip bone mineral density scores were
      the most important predictors of mortality, while biochemical androgen markers
      and Short-Form 36 Physical Domain questions were the most important predictors of
      immobility. Sarcopenia assessed by lean mass estimates was relevant to mortality
      prediction but not immobility prediction. CONCLUSIONS: Using advanced statistical
      models and a machine learning approach 5-year mortality can be predicted with
      good accuracy using a Bayesian generalized linear model and 3-year incident
      severe immobility with fair accuracy using a multivariate adaptive regression
      splines model.

PMID- 29569153
TI  - Risk of fragility fracture among patients with sarcoidosis: a population-based
      study 1976-2013-supplementary presentation.
AB  - Incidence of fragility fracture of a population-based cohort of 345 patients with
      sarcoidosis was compared with age- and sex-matched comparators. The incidence of
      fragility fracture was higher among patients with sarcoidosis with a hazard ratio
      (HR) of 2.18.

PMID- 29569154
TI  - Variations in Endosymbiont Infection Between Buprofezin-Resistant and Susceptible
      Strains of Laodelphax striatellus (Fallen).
AB  - The endosymbionts Wolbachia and Rickettsia have been shown to be correlated with
      the insecticide resistance of mosquito and whitefly. The small brown planthopper
      (SBPH), Laodelphax striatellus, harbours many species of endosymbionts, and has
      developed a high resistance to buprofezin in China. In this study, we examined
      the species and the infection incidences of endosymbionts in a buprofezin
      resistant (BR) strain, a buprofezin-susceptible (BS) strain, and the BR strain
      after exposure to buprofezin, and we also investigated the change in buprofezin
      susceptibility after removal of Wolbachia from the BR strain. The results showed
      that Wolbachia infection incidences were 100% in both the BR and BS strains, but
      the Wolbachia density in the BR strain was significantly higher than that in the
      BS strain. There were no significant differences in Arsenophonus infection
      incidence between the two strains. However, the infection incidence of Serratia
      and double infection incidence of Serratia + Wolbachia in the BR strain were
      significantly higher than that in the BS strain. After the BR strain was exposed
      to 1200 mg/L buprofezin, the infection incidence of Arsenophonus in the surviving
      individuals increased, and the infection rate of Serratia did not differ, but the
      double infection incidence of Serratia + Wolbachia decreased. And when a
      Wolbachia-infected line originating from the BR strain was cleared of Wolbachia,
      its susceptibility to buprofezin increased. The results suggest that Serratia and
      Wolbachia infection might improve the buprofezin resistance of SBPH.

PMID- 29569155
TI  - Formulation Development and Evaluation of Diphenhydramine Nasal Nano-Emulgel.
AB  - The aim of present study is to formulate diphenhydramine nasal nano-emulgels,
      having lipophilic nano-sized interior droplets, with better penetration for
      targeted controlled delivery to mucous membrane. Different diphenhydramine (DPH)
      nasal nano-emulgels were developed having propylene glycol and olive oil (as
      permeation enhancers) by using RSM for optimization and then evaluated for
      physico-chemical characteristics and thermal stability. In-vitro drug release
      through cellophane membrane was conducted and results were analyzed
      statistically. Further, gelation, mucoadhesive stress, and ex-vivo and
      histopathological studies were performed on optimized formulation by using goat
      nasal membrane. Among all formulations, E2 showed maximum DPH release at higher
      concentration olive oil (4%) and lower concentration propylene glycol (PG) (25%)
      within 4 h. All formulations have followed first-order kinetics and drug release
      mechanism was Fickian diffusion. Analysis of variance (ANOVA) and multiple linear
      regression analysis (MLRA) were used to compare results among formulations and 3D
      surface plots were constructed also. Optimized formulation showed immediate
      prolong gelation in artificial nasal mucosa and excellent mucoadhesive property
      (72.5 +/- 1.5 dynes/cm2). Approximately 97.1% optimized formulation was permeated
      through membrane within 4 h, having a high flux rate (33.19 +/- 0.897
      MUg/cm2/min) with diffusion coefficient (0.000786 +/- 4.56 * 10-5 cm2/min) while
      drug contents remained on mucosal membrane for 24 h. Histopathologically, change
      on intra-mucosal surface of excised membrane was observed due to passage of drug
      through it. In summary, combination of PG and olive oil in nasal DPH nano-emulgel
      can be utilized successfully for targeted controlled delivery. The optimized
      formulation has excellent permeability and prolonged residence time on mucosal
      surface, which prove its good anti-histaminic activity in case of allergic
      rhinitis.

PMID- 29569156
TI  - Which organ dysfunction scores to use in children with infection?

PMID- 29569157
TI  - Selection and regeneration of Vitis vinifera Chardonnay hydroxyproline-resistant
      calli.
AB  - Proline (Pro) accumulation protects plant cell under abiotic stress.
      Hydroxyproline (Hyp) as selection agent is a toxic analog of proline and promotes
      Pro overaccumulation. In this study, Chardonnay calli were firstly irradiated
      with different dosages of 60Co and then cultured on a Hyp-added medium. Finally,
      some stable hydroxyproline-resistant (HR) calli were obtained. When calli were
      cultured on 4 mM Hyp medium for 7 days, intracellular Pro content of the HR calli
      was five times higher than that detected in the normal calli. The regeneration of
      HR calli into plantlets was much slower than that of normal ones. When cultured
      on woody plant medium (WPM) containing 10 mM NaCl for 14 days, HR plantlets still
      grew well with lower Pro than withered normal plantlets. qRT-PCR results of Pro
      biosynthesis-related genes in HR plantlets showed that three genes VvP5CS, VvOAT,
      and VvP5CDH were conducive for Pro accumulation. These results confirmed that HR
      plantlets acquired salt tolerance ability. We prospect that this procedure to
      obtain salt-tolerant plants may be valuable to breed programs and improve
      grapevine genotypes with increased tolerance to salt and other abiotic stresses.

PMID- 29569158
TI  - Cut-off values of and factors associated with a negative influence on Neck
      Disability Index.
AB  - PURPOSE: The Neck Disability Index (NDI) is used to evaluate patients with
      cervical spine disease. However, few reports have defined the cut-off values of
      the NDI. The purpose of this study was to identify the cut-off values of and
      factors with a negative impact on NDI. METHODS: A total of 487 volunteers were
      divided into three groups based on disability: none, mild, and disabled. The cut
      off values of the NDI were determined using receiver-operating characteristic
      curves. After these groups were divided based on sex and age adjustment was
      performed, the factors with a negative impact on NDI were investigated using
      multiple logistic regression analysis. RESULTS: Groups none, mild, and disabled
      included 207, 186, and 94 volunteers, respectively. The cut-off values of the NDI
      in each group were 0-5, 6-17, and >= 18%, respectively. After adjusting for age,
      groups none, mild, and disabled had 65, 56, and 23 males, respectively, and 92,
      103, and 56 females, respectively. In multiple logistic regression analysis, the
      factors with a negative impact on NDI in males were manual work (odds ratio [OR]
      1.924), higher T1 slope minus cervical lordosis (OR 1.043), and higher C2-7
      sagittal vertical axis (OR 1.029, P < 0.05). Among females, the factors were hand
      grip strength (OR 0.936), body fat percentage (OR 0.942), and sporting activity
      (OR 0.456, P < 0.05). CONCLUSION: Deterioration in NDI was associated with
      cervical spinal malalignment and manual labor in males and lack of physical
      activity and sarcopenia in females. These slides can be retrieved under
      Electronic Supplementary Material.

PMID- 29569159
TI  - Percutaneous cement discoplasty for the treatment of advanced degenerative disk
      disease in elderly patients.
AB  - PURPOSE: The authors describe a percutaneous technique to treat advanced
      degenerative disk disease in elderly patients. METHOD: A step-by-step technical
      description based on our experience in selected cases. RESULT: Postoperative
      imaging results are presented as well as indications and recommendations.
      CONCLUSION: Percutaneous discoplasty can result as an alternative minimal
      invasive strategy for the treatment of advanced degenerative disk disease.

PMID- 29569160
TI  - Erratum to: Oxytocin Signaling in the Early Life of Mammals: Link to
      Neurodevelopmental Disorders Associated with ASD.

PMID- 29569161
TI  - Genetic variation of 17 X-chromosome STR loci in Tunisian population of Nabeul.
AB  - In the present study, the genetic variations of 17 X-STR markers (DXS8378,
      DXS9898, DXS7133, GATA31E08, GATA172D05, DXS6801, DXS7423, DXS6809, DXS6799,
      DXS7132, DXS9902, DXS6800, DXS6789, DXS10075, DXS10079, DXS6807, and DXS6803)
      were analyzed in 139 unrelated individuals in Nabeul, aiming to perform an X-STR
      database for anthropological and forensic purposes. Our results indicate that
      DXS6809 was the most polymorphic locus, whereas DXS6807 was the least informative
      marker. In addition, the obtained values for the statistical parameters of
      forensic interest, i.e., the power of discrimination in males (PDM) and females
      (PDF), as well as the mean exclusion chance in duos (MECD) and trios (MECT) have
      demonstrated that this panel of 17 X-STRs is highly informative and useful for
      forensic application and anthropological research. Additionally, pairwise genetic
      distances based on FST were calculated between Nabeul population and other
      populations extracted from the literature. Genetic distances were represented in
      a non-metric MDS plot and clustering of populations according to their geographic
      locations and their historical relationship was detected.

PMID- 29569162
TI  - Cranial secular change from the nineteenth to the twentieth century in modern
      German individuals compared to modern Euro-American individuals.
AB  - Studying secular changes on human skulls is a central issue in anthropological
      research, which is however insufficiently investigated for modern German
      populations. With our study, we focus on morphological cranial variations within
      Germans during the nineteenth and twentieth centuries. To study this, we recorded
      different facial landmarks from a cohort study of about 540 German individuals of
      different age and sex by calculating their cranial size, shape dimensions, and
      cranial module and cranial capacity to get information about variations occurring
      during the decades. According to this, measured variables for Germans and
      Americans, to which we compared our results, were maximum cranial length
      (glabello-occipital length), basion-bregma height (BBH), basion-nasion length
      (BNL), maximum cranial breadth (XCB), and cranial base breadth (AUB). Cranial
      size was calculated as the geometric mean of GOL, BBH, and XCB. Samples were
      organized into quarter century birth cohorts, with birth years ranging from 1800
      to 1950. One-way ANOVA was used to test for variation among cohorts. Over the
      past 150 years, Americans and Germans showed significant parallel changes, but
      the American cranium remained relatively higher, with a longer cranial base, as
      well as narrower than the German cranium. Our results should also lead to the
      extension of the range of populations listed and investigated for Fordisc(r), a
      forensic software to identify unknown individuals as from their skeletal remains
      or just parts of them. Fordisc cannot provide a satisfying identification of
      European individuals yet because the database is missing enough European
      reference samples.

PMID- 29569163
TI  - Reclassification of 400 consecutive glioma cases based on the revised 2016WHO
      classification.
AB  - In this study, we reclassified 400 consecutive glioma cases including pediatric
      cases, using the revised 2016 WHO classification with samples collected from the
      Kyushu University Brain Tumor Bank. The IDH1/2, H3F3A, key genetic markers in the
      2016 classification, were analyzed using high-resolution melting, with DNA
      extracted from frozen tissues. The 1p/19q codeletions were evaluated using a
      microsatellite-based loss of heterozygosity analysis, with 18 markers, to detect
      loss of the entire chromosome arm. In the integrated diagnosis, 29
      oligodendroglioma cases and 28 anaplastic oligodendroglioma cases were diagnosed
      as "IDH-mutant and 1p/19q-codeleted," while 2 oligodendroglioma cases and 5
      anaplastic oligodendroglioma cases were diagnosed as not otherwise specified
      (NOS). These "NOS" cases were either IDH-mutants or 1p/19q-codeleted, although
      characteristic oligodendroglial features were evident histologically. Better
      overall survival of patients with oligodendroglioma correlated with the molecular
      characteristic of "IDH-mutant and 1p/19q-codeleted," rather than the WHO grade.
      Eleven "glioblastoma, IDH-wild-type" cases were classified as "1p/19q-codeleted",
      however, chromosome 10 loss was also detected in 10 out of 11 cases. The 2016 WHO
      criteria for glioma classification leads to better diagnosis of patients.
      However, there are technical pitfalls and problems to be solved in the molecular
      analysis of routine diagnostics.

PMID- 29569165
TI  - Theoretical study of the electronic structure of mono-chloride of lanthanum
      molecule including spin-orbit coupling effect.
AB  - Our investigation is devoted to the theoretical study of the low-lying electronic
      structure of the LaCl molecule by using ab initio quantum methods. We are
      concerned with several methods such as the complete active space-self consistent
      field (CAS-SCF) and the multi reference of configuration interaction (MRCI + Q)
      methods. These methods are applied for the purpose of drawing the potential
      energy curves (PECs) and calculating the molecular spectroscopic constants for a
      given number of electronic states of singlet and triplet multiplicity. We count
      26 2S+ 1 Lambda(+/-) electronic states located below 24,000 cm- 1 neglecting the
      spin-orbit effects and 47 Omega(+/-) components taken into consideration these
      effects. Our calculations are performed via the quantum ab initio package MOLPRO
      (Werner and Knowles 2000). Graphical Abstract A new set of low-lying electronic
      states on the theoretical energetic level diagram for the LaCl molecule among the
      first four lanthanum monhalides.

PMID- 29569166
TI  - Correction to: Internalizing and Externalizing Behaviors Share a Common
      Predictor: the Effects of Early Maladaptive Schemas Are Mediated by Coping
      Responses and Schema Modes.
AB  - The authors would like to note that one of the co-author's names was displayed
      incorrectly. Not Arnoud A. Arntz, but Arnoud Arntz co-authored this article as
      shown above.

PMID- 29569164
TI  - Prognostic and Predictive Factors for Renal Cell Carcinoma.
AB  - Metastatic renal cell carcinoma (mRCC) is an incurable malignancy, characterized
      by its resistance to traditional chemotherapy, radiation, and hormonal therapy.
      Treatment perspectives and prognosis of patients with mRCC have been
      significantly improved by advances in the understanding of its molecular
      pathogenesis, which have led to the development of targeted therapeutics.
      Different molecular factors derived from the tumor or the host detected in both
      tissue or serum could be predictive of therapeutic benefit. Some of them suggest
      a rational selection of patients to be treated with certain therapies, though
      none have been validated for routine use. This article provides an overview of
      both clinical and molecular factors associated with predictive or prognostic
      value in mRCC and emphasizes that both should be considered in parallel to
      provide the most appropriate, individualized treatment and achieve the best
      outcomes in clinical practice.

PMID- 29569167
TI  - Microdroplets Accelerate Ring Opening of Epoxides.
AB  - The nucleophilic opening of an epoxide is a classic organic reaction that has
      widespread utility in both academic and industrial applications. We have studied
      the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4
      (prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed
      microdroplets with a 1:1 v/v water/methanol solvent system. We find that even
      after 90 min at room temperature, there is no product detected by nuclear
      magnetic resonance spectroscopy in bulk solution whereas in room-temperature
      microdroplets (2-3 MUm in diameter), the yield is already 0.5% in a flight time
      of 1 ms as observed by mass spectrometry. This constitutes a rate acceleration of
      ~ 105 in the microdroplet environment, if we assume that as much as 5% of product
      is formed in bulk after 90 min of reaction time. We examine how the reaction rate
      depends on droplet size, solvent composition, sheath gas pressure, and applied
      voltage. These factors profoundly influence the extent of reaction. This dramatic
      acceleration is not limited to just one system. We have also found that the
      nucleophilic opening of cis-stilbene oxide by morpholine is similarly
      accelerated. Such large acceleration factors in reaction rates suggest the use of
      microdroplets for ring opening of epoxides in other systems, which may have
      practical significance if such a procedure could be scaled. Graphical Abstract
      This graphical image is distorted.  It is too extended in the vertical direction.
      Please fix.?.

PMID- 29569168
TI  - Development of decellularized amniotic membrane as a bioscaffold for bone marrow
      derived mesenchymal stem cells: ultrastructural study.
AB  - Developing effective stem cell-based therapies requires the design of complex in
      vitro culture systems for accurate representation of the physiological stem cell
      niche. Human amniotic membrane (hAM) has been successfully used in clinical
      grafting applications due to its unique biological and regenerative properties.
      Decellularized hAM (d-hAM) has been previously applied to the culture of human
      bone marrow mesenchymal stem cells (hMSCs), promoting their expansion and
      differentiation into adipogenic and osteogenic lineages. In the present study,
      hAM was decellularized by NaOH-treatment, to provide the three-dimensional (3D)
      bioscaffold for culturing hMSCs. The ultrastructural differences between intact
      hAM and decellularized hAM were characterized using the transmission electron
      microscope (TEM), as well as the 3D interaction between d-hAM and hMSCs cultured
      on the membrane. TEM examination of the intact hAM showed many microvilli on the
      epithelial layer cells, active Golgi apparatus, smooth endolplasmic reticulum and
      the characteristic pinocytic vesicles. The epithelial layer with its structures
      was absent in the d-hAM. However, no observable difference was detected in the
      ultrastructural characteristics of the compact stromal layer of d-hAM compared to
      intact hAM. Both contained bundles of extra cellular matrix (ECM) proteins, and
      scattered elastic fibres. Cultured human mesenchymal stem cells (hMSCs) examined
      by TEM appeared oval to spherical in shape and had a rough and non-uniform
      surface with distinct protrusions or irregular fillopodia. Their diameter ranged
      from 20.49 to 21.6 um. Most of the cellular organelles were also noticed. SEM
      examination of the prepared samples revealed unique 3D interaction between the
      hMSC and d-hAM, where the latter seems to envelop the segments of the hMSCs lying
      on the surrounding membrane. This study shows that the decellularization process
      affected the epithelial layer only of hAM and had no effect on altering the
      presence of ECM components present in the stromal layer of the d-hAM. The
      interaction between hMSCs and d-hAM maybe mediated by hAM components other than
      human amniotic epithelial cells, such as ECM components or MSCs present in the
      deeper spongy layer of the membrane or/and the adhesive components of the
      basement membrane of the removed epithelial layer.

PMID- 29569170
TI  - Floral structure and development in Nartheciaceae (Dioscoreales), with special
      reference to ovary position and septal nectaries.
AB  - We present a comparative study of the floral structure and development of
      Nartheciaceae, a small dioscorealean family consisting of five genera (Aletris,
      Lophiola, Metanarthecium, Narthecium, and Nietneria). A noticeable diversity
      existed in nine floral characters. Analyses of their respective character states
      in the light of a phylogenetic context revealed that the flowers of
      Nartheciaceae, whose plesiomorphies occur in Aletris and Metanarthecium, have
      evolved toward in all or part of Lophiola, Narthecium, and Nietneria: (1) loss of
      a perianth tube; (2) stamen insertion at the perianth base; (3) congenital carpel
      fusion; (4) loss of the septal nectaries; (5) unilocular style; (6) unfused
      lateral carpellary margins in the style; (7) flower with the median outer tepal
      on the abaxial side; (8) flower with moniliform hairs; and (9) flower with weak
      monosymmetry. We further found that, as the flowers developed, the ovary shifted
      its position from inferior to superior. As a whole, their structure changes
      suggest that the Nartheciaceae flowers have evolved in close association with
      pollination and seed dispersal. By considering inferior ovaries and the presence
      of septal nectaries as plesiomorphies of Nartheciaceae, we discussed evolution of
      the ovary position and septal nectaries in all the monocots.

PMID- 29569169
TI  - Flower-like heads from flower-like meristems: pseudanthium development in Davidia
      involucrata (Nyssaceae).
AB  - Flower-like inflorescences (pseudanthia) have fascinated botanists for a long
      time. They are explained as condensed inflorescences implying that the
      pseudanthium develops from an inflorescence meristem (IM). However, recent
      developmental studies identified a new form of reproductive meristem, the floral
      unit meristem (FUM). It differs from IMs by lacking acropetal growth and shares
      fractionation, expansion and autonomous space filling with flower meristems (FM).
      The similarity among FUMs and FMs raises the question how far flower-like heads
      originate from flower-like meristems. In the present paper, pseudanthium
      development in Davidia involucrata is investigated using scanning electron
      microscopy. D. involucrata has pincushion-shaped heads composed of densely
      aggregated, perianthless flowers and associated with two large showy bracts.
      Early developmental stages show a huge naked FUM. The FMs appear almost
      simultaneously and lack subtending bracts. With ongoing FUM expansion new space
      is generated which is immediately used by further FM fractionation. The heads
      have only staminate flowers or are andromonoecious with staminate and a single
      perfect flower in oblique position. All FMs lack perianth structures and
      fractionate a variable number of stamen primordia. The perfect FM is much larger
      than the staminate FMs and forms a syncarpous gynoecium with inferior ovary.
      Pseudanthium development in D. involucrata confirms the morphogenetic similarity
      to FMs as to acropetal growth limitation, meristem expansion and fractionation.
      It thus should not be interpreted as a condensed inflorescence, but as a flower
      equivalent. Furthermore as the FUM develops inside a bud, its development is
      considered to be influenced by mechanical pressure. The oblique position of the
      perfect flower, the developmental delay of the proximal flowers, and the variable
      number of stamens which were observed in the pseudanthium development, can be
      caused by mechanical pressure. Next to the Asteraceae, D. involucrata offers a
      further example of a pseudanthium originating from a FUM. More knowledge on FUMs
      is still needed to understand diversification and evolution of flower-like
      inflorescences.

PMID- 29569171
TI  - Engineering Ethics Education: A Comparative Study of Japan and Malaysia.
AB  - This paper reports the findings of a comparative study in which students'
      perceived attainment of the objectives of an engineering ethics education and
      their attitude towards engineering ethics were investigated and compared. The
      investigation was carried out in Japan and Malaysia, involving 163 and 108
      engineering undergraduates respectively. The research method used was based on a
      survey in which respondents were sent a questionnaire to elicit relevant data.
      Both descriptive and inferential statistical analyses were performed on the data.
      The results of the analyses showed that the attainment of the objectives of
      engineering ethics education and students' attitude towards socio-ethical issues
      in engineering were significantly higher and positive among Japanese engineering
      students compared to Malaysian engineering students. Such findings suggest that a
      well-structured, integrated, and innovative pedagogy for teaching ethics will
      have an impact on the students' attainment of ethics education objectives and
      their attitude towards engineering ethics. As such, the research findings serve
      as a cornerstone to which the current practice of teaching and learning of
      engineering ethics education can be examined more critically, such that further
      improvements can be made to the existing curriculum that can help produce
      engineers that have strong moral and ethical characters.

PMID- 29569172
TI  - A retrospective evaluation of the perioperative drug use and comparison of its
      cost in robotic vs open surgery for endometrial cancer.
AB  - To compare the usage and cost of analgesics (opioid and non-opioids),
      antiemetics, and IV fluids and its associated costs in robotic vs open staging
      surgery for endometrial cancer (EC). This retrospective study was performed at a
      single academic institution from January 2014 to June 2017 in the department of
      Gynecology Oncology at Amrita Institute of Medical Science, Kerala, India. The
      study included women with biopsy confirmed clinically early stage endometrial
      cancer or atypical hyperplasia, who underwent robotic-assisted or open staging
      surgery. Data on surgical time, blood loss, post-anaesthesia care unit (PACU)
      stay, and length of hospital (LOH) stay; analgesic, antiemetic, and IV fluid use
      were collected for three distinct periods: intra-operative, PACU, and ward.
      Direct medicine and material costs associated with the administration of
      intravenous (IV) fluids, analgesics, and antiemetics were collected. All
      parameters were compared between two surgical groups. The study included 133 (54
      open and 79 robotic-assisted) patients. As compared to open surgery, robotic
      assisted surgery was associated with significantly reduced: surgical time (p =
      0.007), estimated blood loss (p < 0.001), PACU stay (p < 0.001), LOH stay (p <
      0.001); IV fluids (crystalloid and colloid; p < 0.001); opioids (p < 0.001), non
      opioids (intravenous acetaminophen, oral acetaminophen, diclofenac; all p <
      0.001); incidence of post-operative nausea and vomiting and the requirement of
      rescue antiemetics (p < 0.001). EC staging using robotic-assisted surgery was
      associated with significantly lower medicine and material costs attributed to IV
      fluids, analgesia, and antiemetics (p < 0.001). As compared to open surgery,
      robotic surgery was associated with the total saving of $107.7 ($19.5 in IV
      fluids, $49.2 in analgesics, $1.33 in antiemetics, and $37.8 in material).
      Robotic-assisted surgical staging for endometrial cancer is associated with
      decreased requirement and expenditure attributable to post-operative pain, post
      operative nausea and vomiting, and maintenance and replacement fluid therapy.

PMID- 29569173
TI  - Ultrastructural Changes and Expression of PCNA and RPE65 in Sodium Iodate-Induced
      Acute Retinal Pigment Epithelium Degeneration Model.
AB  - Alteration in retinal pigment epithelium (RPE) results in the visual dysfunction
      and blindness of retinal degenerative diseases. Injection of sodium iodate
      (NaIO3) generates degeneration of RPE. We analyzed the sequential ultrastructure
      and expression of proliferating cell nuclear antigen (PCNA) and retina-specific
      RPE65 in NaIO3-induced retinal degeneration model. Adult male rats were injected
      1% NaIO3 (50 mg/kg) and eyes were enucleated at 1, 3, 5, 7 and 14 days post
      injection (DPI), fixed, and processed for histological analysis. NaIO3-induced
      retinal degeneration was successfully established. At 1 DPI, most RPE cells were
      degenerated and replaced by a few proliferating RPE cells in the peripheral area.
      At 3 DPI, the RPE and photoreceptor out segments (POS) underwent a marked
      morphological change, including POS disruption, accumulation of residual bodies
      in RPE and POS, and hyperplasia of the RPE cell. At 5 DPI, POS showed a maximum
      increase in the outer segment debris and the retina showed partial detachment.
      These abnormal morphological changes gradually decreased by day 7. At 14 DPI, the
      damaged RPE and POS were partially regenerated from the peripheral to the central
      region. Expression of PCNA and RPE65 increased from day 3 onward. The damaged RPE
      showed earlier expression of PCNA and RPE65 than POS. The RPE damaged by NaIO3
      rapidly proliferated to put down roots on Bruch's membrane from the peripheral
      retina and proliferation and hyperplasia of the RPE had a regular direction of
      progress. Therefore, NaIO3-induced acute changes in retina mimic the patho
      morphologic features of RPE-related diseases.

PMID- 29569174
TI  - Relationship between Organizational Culture and the Use of Psychotropic Medicines
      in Nursing Homes: A Systematic Integrative Review.
AB  - BACKGROUND: Psychotropic medicines are commonly used in nursing homes, despite
      marginal clinical benefits and association with harm in the elderly.
      Organizational culture is proposed as a factor explaining the high-level use of
      psychotropic medicines. Schein describes three levels of culture: artifacts,
      espoused values, and basic assumptions. OBJECTIVE: This integrative review aimed
      to investigate the facets and role of organizational culture in the use of
      psychotropic medicines in nursing homes. METHOD: Five databases were searched for
      qualitative, quantitative, and mixed method empirical studies up to 13 February
      2017. Articles were included if they examined an aspect of organizational culture
      according to Schein's theory and the use of psychotropic medicines in nursing
      homes for the management of behavioral and sleep disturbances in residents.
      Article screening and data extraction were performed independently by one
      reviewer and checked by the research team. The integrative review method, an
      approach similar to the method of constant comparison analysis was utilized for
      data analysis. RESULTS: Twenty-four studies met the inclusion criteria: 13 used
      quantitative methods, 9 used qualitative methods, 1 was quasi-qualitative, and 1
      used mixed methods. Included studies were found to only address two aspects of
      organizational culture in relation to the use of psychotropic medicines:
      artifacts and espoused values. No studies addressed the basic assumptions, the
      unsaid taken-for-granted beliefs, which provide explanations for in/consistencies
      between the ideal use of psychotropic medicines and the actual use of
      psychotropic medicines. CONCLUSIONS: Previous studies suggest that organizational
      culture influences the use of psychotropic medicines in nursing homes; however,
      what is known is descriptive of culture only at the surface level, that is the
      artifacts and espoused values. Hence, future research that explains the impact of
      the basic assumptions of culture on the use of psychotropic medicines is
      important.

PMID- 29569175
TI  - Cervical dystonia and substance abuse.
AB  - OBJECTIVE: To investigate the prevalence of substance abuse (SA) in patients with
      cervical dystonia (CD) and to correlate it with prevalence of psychiatric
      disorders. METHODS: Data on anxiety, depression, dystonia severity, and substance
      abuse were collected from ten sites participating in the Dystonia Coalition.
      Patients were divided into two groups according to the presence of SA, utilizing
      Structured Clinical Interview for DSM-4 criteria. Wilcoxon Rank-Sum test was used
      to analyze the difference in median scores on the questionnaires between the
      groups. Chi-square test was used to analyze association between opiate and
      benzodiazepine use and SA. Association between TWSTRS severity and SA and
      medication use was assessed. A two-tailed p value of < 0.05 was considered
      significant. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) was used for all
      analyses. RESULTS: Of 208 CD patients, 23 (11%) were identified with SA; 26.3% of
      patients with SA were on opiates compared to 7.2% of CD patients without SA (p =
      0.006). Compared to non-SA patients, those experiencing SA were more likely male
      (88.9%; p = 0.0007), younger (median age 55; p = 0.031), and scored worse on
      questionnaires assessing depression (p = 0.044, p = 0.005), anxiety (p = 0.003),
      and dystonia psychiatric severity (p = 0.033). The median TWSTRS motor severity
      scores were higher in SA patients compared to non-SA patients (20 versus 16, p =
      0.0339). The median TWSTRS total disability, motor, and pain scores were higher
      in patients on opiates than patients who were not (12 versus 8, p = 0.0071; 18.5
      versus 16, p = 0.0243; 12.4 versus 6.7, p = 0.0052, respectively). CONCLUSIONS:
      Potential risk factors for SA in CD patients include younger age and male gender
      with comorbid anxiety, depression and other psychiatric problems. Caution should
      be exercised when prescribing drugs with potential for abuse in these patients.

PMID- 29569177
TI  - Uncommon and/or bizarre features of dementia. Part II.
AB  - In the past decades, clinicians have recognized that dementia may appear as
      atypical or variant syndromes, as well as the typical form. This study aimed at
      describing uncommon or bizarre symptoms/syndromes observed in patients suffering
      from dementia. Medline and Google scholar searches were conducted for relevant
      articles, chapters, and books published before 2017. Search terms used included
      delusional jealousy, delusion of pregnancy, dementia, erotomania, folie a deux,
      and lycanthropy. Publications found through this indexed search were reviewed for
      further relevant references. The uncommon symptoms/syndromes were described as
      case reports and there were no systematic investigations.

PMID- 29569176
TI  - Incidence and outcome of acquired demyelinating syndromes in Dutch children:
      update of a nationwide and prospective study.
AB  - INTRODUCTION: Acquired demyelinating syndromes (ADS) are immune-mediated
      demyelinating disorders of the central nervous system in children. A nationwide,
      multicentre and prospective cohort study was initiated in the Netherlands in
      2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of
      0.15/100,000 per year in the period between 2007 and 2010. In this study, we
      provide an update on the incidence and the long-term follow-up of ADS in the
      Netherlands. METHODS: Children < 18 years with a first attack of demyelination
      were included consecutively from January 2006 to December 2016. Diagnoses were
      based on the International Paediatric MS study group consensus criteria. Outcome
      data were collected by neurological and neuropsychological assessments, and
      telephone call assessments. RESULTS: Between 2011 and 2016, 55/165 of the ADS
      patients were diagnosed with MS (33%). This resulted in an increased ADS and MS
      incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since
      2006 a total of 243 ADS patients have been included. During follow-up (median 55
      months, IQR 28-84), 137 patients were diagnosed with monophasic disease (56%), 89
      with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one
      form of residual deficit including cognitive impairment was observed in 69% of
      all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale
      score of >= 5.5 was reached in 3/89 MS patients (3%). CONCLUSION: The reported
      incidence of ADS in Dutch children has increased since 2010. Residual deficits
      are common in this group, even in monophasic patients. Therefore, long-term
      follow-up in ADS patients is warranted.

PMID- 29569178
TI  - The encapsulation of the gemcitabine anticancer drug into grapheme nest: a
      theoretical study.
AB  - The efficient transport of a drug molecule until its target cell constitutes a
      significant challenge for delivery processes. To achieve such objectives, solid
      nanocapsules that protect the immune system during the transport should be
      developed and controlled at the nanoscale level. From this point of view,
      nanostructures based on graphene sheets could present some promising properties
      due to their ultimate size and dimension. In this work, we present theoretical
      results using DFT calculations, dealing with a graphene-based delivery system.
      Indeed, we demonstrate the stability of the gemcitabine anticancer molecule when
      it is encapsulated into two concave graphene sheets organized as a nest. Quantum
      calculations showed that the most stable state is located inside the nest, which
      is then formed by two layers distanced 6 A from each other. For all the optimized
      systems, we focused on the dependence of the interaction energy on the molecule
      displacements during its entrance in the graphene nest and its exit from it. We
      also analyzed their consequence on the local morphological and electronic charge
      properties. Graphical Abstract Adsorption energy (in eV) of gemcitabine drug
      during its encapsulation inside the nest of grapheneand its release from it.

PMID- 29569179
TI  - Parasite Tolerance and Host Competence in Avian Host Defense to West Nile Virus.
AB  - Competence, or the propensity of a host to transmit parasites, is partly
      underlain by host strategies to cope with infection (e.g., resistance and
      tolerance). Resistance represents the ability of hosts to prevent or clear
      infections, whereas tolerance captures the ability of individuals to cope with a
      given parasite burden. Here, we investigated (1) whether one easy-to-measure form
      of tolerance described well the dynamic relationships between host health and
      parasite burden, and (2) whether individual resistance and tolerance to West Nile
      virus (WNV) were predictable from single cytokine measures. We exposed house
      sparrows (HOSP) to WNV and measured subsequent changes in host performance, viral
      burden, and cytokine expression. We then used two novel approaches (one complex,
      one simpler) to estimate tolerance within-individual HOSP using four separate
      host performance traits. We lastly investigated changes in the expression of pro
      inflammatory cytokine interferon-gamma (IFN-gamma) and anti-inflammatory cytokine
      interleukin-10 (IL-10). Both approaches to estimating tolerance were equivalent
      among WNV-infected HOSP; thus, an easy-to-measure tolerance estimation may be
      successfully applied in field studies. Constitutive expression of IFN-gamma and
      IL-10 were predictive of resistance and tolerance to WNV, implicating these
      cytokines as viable biomarkers of host competence to WNV.

PMID- 29569181
TI  - There and back again: from the origin of life to single molecules.
AB  - What is life? There is hardly a more fundamental question raised by aspiring
      researchers, and one less prone to ever be answered in a scientifically
      satisfying way. In the long, productive and highly influential period of research
      following his Nobel-recognised work on relaxation kinetics, Manfred Eigen made
      seminal contributions towards a quantifiable definition of life, with a strong
      focus on its evolutionary character. In the last years of his time as an active
      researcher, however, he devoted himself to another, purely experimental topic:
      the detection and analysis of single biomolecules in aqueous solution. In this
      short review, I will give an overview of the groundbreaking contributions to the
      field of single molecule research made by Eigen and coworkers, and show that
      both, in its intrinsic motivation, and in its consequences, single molecule
      research strongly relates to the question of the physical-chemical essence of
      life. In fact, research on living systems with single molecule sensitivity will
      always refer the researcher to the question of the simplest possible
      representation, and thus the origin, of any biological phenomenon.

PMID- 29569180
TI  - Light-regulated promoters for tunable, temporal, and affordable control of fungal
      gene expression.
AB  - Regulatable promoters are important genetic tools, particularly for assigning
      function to essential and redundant genes. They can also be used to control the
      expression of enzymes that influence metabolic flux or protein secretion, thereby
      optimizing product yield in bioindustry. This review will focus on regulatable
      systems for use in filamentous fungi, an important group of organisms whose
      members include key research models, devastating pathogens of plants and animals,
      and exploitable cell factories. Though we will begin by cataloging those
      promoters that are controlled by nutritional or chemical means, our primary focus
      will rest on those who can be controlled by a literal flip-of-the-switch:
      promoters of light-regulated genes. The vvd promoter of Neurospora will first
      serve as a paradigm for how light-driven systems can provide tight, robust,
      tunable, and temporal control of either autologous or heterologous fungal
      proteins. We will then discuss a theoretical approach to, and practical
      considerations for, the development of such promoters in other species. To this
      end, we have compiled genes from six previously published light-regulated
      transcriptomic studies to guide the search for suitable photoregulatable
      promoters in your fungus of interest.

PMID- 29569182
TI  - Biochemical characterization of rice xylan O-acetyltransferases.
AB  - MAIN CONCLUSION: Rice xylan is predominantly monoacetylated at O-2 and O-3, and
      14 rice DUF231 proteins were demonstrated to be xylan acetyltransferases.
      Acetylated xylans are the principal hemicellulose in the cell walls of grass
      species. Because xylan acetylation impedes the conversion of cellulosic biomass
      into biofuels, knowledge on acetyltransferases catalyzing xylan acetylation in
      grass species will be instrumental for a better utilization of grass biomass for
      biofuel production. Xylan in rice (Oryza sativa) is predominantly monoacetylated
      at O-2 and O-3 with a total degree of acetylation of 0.19. In this report, we
      have characterized 14 rice DUF231 proteins (OsXOAT1 to OsXOAT14) that are
      phylogenetically grouped together with Arabidopsis xylan acetyltransferases ESK1
      and its close homologs. Complementation analysis demonstrated that the expression
      of OsXOAT1 to OsXOAT7 in the Arabidopsis esk1 mutant was able to rescue its
      defects in 2-O- and 3-O-monoacetylation and 2,3-di-O-acetylation. Activity assay
      of recombinant proteins revealed that all 14 OsXOATs exhibited acetyltransferase
      activities capable of transferring acetyl groups from acetyl-CoA to the
      xylohexaose acceptor with 10 of them having high activities. Structural analysis
      of the OsXOAT-catalyzed products showed that the acetylated structural units
      consisted mainly of 2-O- and 3-O-monoacetylated xylosyl residues with a minor
      amount of 2,3-di-O-acetylated xylosyl units, which is consistent with the acetyl
      substitution pattern of rice xylan. Further kinetic studies revealed that
      OsXOAT1, OsXOAT2, OsXOAT5, OsXOAT6 and OsXOAT7 had high affinity toward the
      xylohexaose acceptor. Our results provide biochemical evidence indicating that
      OsXOATs are acetyltransferases involved in xylan acetylation in rice.

PMID- 29569183
TI  - TRPV4 is functionally expressed in oligodendrocyte precursor cells and increases
      their proliferation.
AB  - Oligodendrocytes, which differentiate from oligodendrocyte precursor cells
      (OPCs), ensheath axons with myelin, play an essential role in rapid conduction of
      action potentials and metabolically support neurons. Elucidation of the
      mechanisms underlying the proliferation, migration, differentiation, and survival
      of OPCs is considered indispensable for determining the causes of central nervous
      system diseases. However, the relationship between these functions of OPCs and
      their intracellular Ca2+ signaling has not been fully elucidated. Here, we
      investigated the function of transient receptor potential vanilloid 4 (TRPV4), a
      Ca2+-permeable channel that responds to hypo-osmolarity, mild temperature,
      mechanical stimulation, and endogenous arachidonic acid metabolites, in OPCs.
      Trpv4 mRNA was detected in OPCs in vivo and in primary cultured rat OPCs. In Ca2+
      imaging experiments, treatment with the selective TRPV4 agonist GSK1016790A
      induced sustained elevation of the intracellular Ca2+ concentration in OPCs in a
      concentration-dependent manner, which was almost completely suppressed by co
      treatment with the selective TRPV4 antagonist HC067047. Stimulation of TRPV4 by
      GSK1016790A augmented OPC proliferation, which was abolished by co-treatment with
      HC067047, the intracellular Ca2+ chelator BAPTA-AM, and the protein kinase C
      inhibitor bisindolylmaleimide II. By contrast, GSK1016790A did not significantly
      affect the migration or differentiation of OPCs. Taken together, these results
      suggest that TRPV4 is functionally expressed in OPCs and increases the
      proliferation of these cells without affecting their ability to differentiate
      into oligodendrocytes.

PMID- 29569184
TI  - Mucosal Melanoma: a Literature Review.
AB  - PURPOSE OF REVIEW: Mucosal melanoma is of great interest due to its aggressive
      behavior and less favorable prognosis. The literature is mainly case reports and
      case series. Here, we will collect the knowledge on mucosal melanoma from the
      last decade and review the literature. The main focus is being site-specific
      clinical features, treatment, and prognosis. RECENT FINDINGS: The use of
      immunotherapy gain ground as for others subsets of melanoma. Anti-CTLA-4 and anti
      PD-1/ PD-L1 blockade in mucosal melanoma have been evaluated in recent studies.
      Clinical trials are ongoing. The etiology of mucosal melanomas remains unknown.
      Head and neck mucosal melanomas are most common. Wide excision surgery is the
      treatment of choice. The effect of adjuvant therapy on survival remains
      questionable due to the limited knowledge. Radiotherapy seems to give better
      local control. The overall five-year survival rate for mucosal melanomas is 0
      45%. Recent data indicates that this may be improved by the immunotherapy in the
      years to come.

PMID- 29569185
TI  - Indications and results of renal biopsy in children: a 36-year experience.
AB  - BACKGROUND: This study was conducted to investigate retrospectively the
      indications for renal biopsy (RB) in native kidneys and to analyze pathological
      findings in a single tertiary pediatric hospital in Southern Italy for the last
      36 years. METHODS: All patients who underwent RB at our hospital from 1979 to
      2014 were included. All renal tissue specimens were studied under light and
      immunofluorescent microscopy, while electron microscopy was performed only for
      specific clinical indications. RESULTS: The study group included 213 patients
      (female 43.2%) who underwent 225 percutaneous native kidney biopsies. Median age
      was 10.4 years (range 0.6-24 years). The most frequent indication for RB was
      nephrotic syndrome (44.4%), followed by proteinuria (27.6%), asymptomatic
      hematuria (17.3%) and acute kidney injury (9.8%). Gross hematuria appeared after
      biopsy in less than 5% of the patients, but none of them needed blood
      transfusion. Adequate renal tissue sample was obtained in 95.5% of the renal
      biopsies. Primary glomerulonephritis (GN) was the most common finding (61.4%),
      followed by secondary GN (21.4%), tubulointerstitial diseases (3.7%) and
      hereditary nephropathy (2.8%), while in 10.7% of the cases, normal renal tissues
      were found. According to histopathological diagnosis, the most common causes of
      primary GN were IgA nephropathy (20.9%), followed by minimal change disease
      (18.1%) and focal segmental glomerulosclerosis (11.6%). CONCLUSIONS: The
      epidemiology of glomerular disease in our single-center cohort is similar to that
      shown in other national and international reports. Moreover, our study shows that
      percutaneous ultrasound-guided RB is a safe, reliable and effective technique in
      children.

PMID- 29569188
TI  - Age of Onset in Pedohebephilic Interests.

PMID- 29569186
TI  - Takotsubo Syndrome: Clinical Features, Pathogenesis, Treatment, and Relationship
      with Cerebrovascular Diseases.
AB  - PURPOSE OF REVIEW: This review paper aims to provide a complete and updated
      overview on the clinical and pathophysiological aspects of Takotsubo syndrome
      (TTS), including prognosis, therapy, and the association with cerebrovascular
      conditions. RECENT FINDINGS: TTS is an increasingly recognized non-ischemic
      cardiomyopathy characterized by sudden, temporary weakening of the myocardium, of
      which the pathogenesis is unknown. Although pathogenesis of TTS remains unclear,
      a complex interaction between catecholamine-mediated stimulation, myocardial
      stunning, and subsequent stress-related myocardial dysfunction seems to be the
      main pathophysiological mechanism. Stroke is linked to TTS by a dual relationship
      since it may induce TTS by catecholamine release even if TTS itself also may be
      complicated by left ventricular thrombi leading to stroke. Given its possible
      complications, including the association with neurological diseases, both
      cardiologist and neurologists should be aware about TTS in order to diagnose it
      promptly and to initiate appropriate therapeutic measures.

PMID- 29569187
TI  - Gender Differences in the Structure of Marital Quality.
AB  - Marriages consist of shared experiences and interactions between husbands and
      wives that may lead to different impressions of the quality of the relationship.
      Few studies, unfortunately, have tested gender differences in the structure of
      marital quality, and even fewer studies have evaluated whether genetic and
      environmental influences on marital quality differ across gender. In this study,
      we evaluated gender differences in the structure of marital quality using
      independent samples of married male (n = 2406) and married female (n = 2215)
      participants from the National Survey of Midlife Development in the United States
      who provided ratings on twenty-eight marital quality items encompassing six
      marital quality constructs. We further explored gender differences in genetic and
      environmental influences on marital quality constructs in a subsample of 491
      pairs of twins. Results suggest partial metric invariance across gender but
      structural variability in marital quality constructs. Notably, correlations
      between constructs were stronger in women than men. Results also support gender
      differences in the genetic and environmental influences on different aspects of
      marital quality. We discuss that men and women may approach and react to marriage
      differently as the primary reason why we observed differences in the structure of
      marital quality.

PMID- 29569190
TI  - HIF stabilizers in the management of renal anemia: from bench to bedside to
      pediatrics.
AB  - Anemia is a common complication of chronic kidney disease (CKD) in adult and
      pediatric patients. It has traditionally been treated with erythropoietin therapy
      and iron supplementation, with great success. With the discovery of the major
      transcription factor hypoxia inducible factor (HIF) for the erythropoietin gene
      in 1992, molecules were created that inhibit the HIF prolyl-hydroxylase enzyme.
      This new class of drug-called HIF stabilizers, or HIF prolyl-hydroxylase
      inhibitors-prevents the proteasomal degradation of HIF-alpha, thereby inducing
      upregulation of the erythropoietin gene. This new strategy for treating CKD
      anemia is already in phase III clinical trials in adults, and the potential
      advantages of this therapy are that it is orally active (thereby avoiding
      injections), and patients are exposed to lower circulating levels of
      erythropoietin. The long-term safety of this strategy, however, requires
      elucidation in these trials, particularly since there are many other hypoxia
      sensitive genes, notably, angiogenic factors such as vascular endothelial growth
      factors (VEGF), as well as glycolytic enzymes. As with all new therapies, it is
      only once a positive benefit: risk profile has been ascertained in adults that
      the treatment will translate across into pediatrics. Specific issues in the
      pediatric CKD population are discussed in this review.

PMID- 29569189
TI  - Life Satisfaction Across Adulthood in Bisexual Men and Women: Findings from the
      Midlife in the United States (MIDUS) Study.
AB  - The number of lesbian, gay, and bisexual (LGB) adults aged 50 and older is
      projected to reach 5 million in the U.S. by 2030 (Fredriksen-Goldsen, Kim, Shiu,
      Goldsen, & Emlet, 2015). Older bisexuals experience more negative mental and
      physical health outcomes when compared to both heterosexuals and other sexual
      minorities (Fredriksen-Goldsen, Shiu, Bryan, Goldsen, & Kim, 2017). As bisexuals
      are the numeric majority of sexual minorities in the U.S. (Herbenick et al.,
      2010), bisexual aging processes are critical to understand if researchers wish to
      reduce sexual minority health disparities and promote healthy aging. In the
      current study, we use a national probability sample of adults from the Midlife in
      the United States (MIDUS) study to assess life satisfaction across an 18-year
      period. We aimed to identify whether life satisfaction-an indicator of
      psychological health and well-being-is similar for same-age bisexual, lesbian and
      gay, and heterosexual midlife individuals, and whether sexual orientation
      predicts change in life satisfaction across adulthood. Further, we tested whether
      life satisfaction among bisexuals changes at the same rate and in the same
      pattern as for lesbian, gay, and heterosexual individuals. Overall, we found a
      linear pattern of increase in life satisfaction across adulthood. However, when
      we accounted for sexual orientation, a different pattern emerged for bisexuals.
      Whereas heterosexuals and lesbian and gay individuals experienced increases in
      life satisfaction across adulthood, bisexuals' life satisfaction did not increase
      over this period. Implications for bisexual health and well-being are discussed.

PMID- 29569191
TI  - Urinary CD80 excretion is a predictor of good outcome in children with primary
      nephrotic syndrome.
AB  - BACKGROUND: The level of urinary cluster of differentiation 80 (uCD80) is
      elevated in most children with minimal change disease (MCD) as opposed to focal
      segmental glomerulosclerosis (FSGS) during the acute phase. The objective of this
      follow-up study was to evaluate whether uCD80 elevation is actually associated
      with MCD and whether it signals better prognosis. METHODS: We evaluated uCD80
      levels and a series of putative progression factors in a cohort of 64 patients
      with nephrotic syndrome (NS) seen between 2011 and 2016. We monitored progression
      of chronic kidney disease (CKD), assessed as a glomerular filtration rate of < 90
      ml/min/1.73 m2 for at least 3 months. Patients were classified according to uCD80
      level and to the progression rate as calculated by Kaplan-Meier survival analysis
      and Cox's regression analysis. RESULTS: During a mean follow-up period of 4.8 +/-
      0.6 (range 3.5-6.0) years, 13 children (20%) evolved to at least CKD stage 2. The
      64 patients with NS and normal baseline renal function were divided into two
      groups based on uCD80 excretion, i.e. below or above a defined cutoff (< or >
      328.98 ng/g creatinine). The predicted response to immunosuppression therapy was
      34.5 and 100% in the low- and high-uCD80 excretion, respectively (p < 0.001).
      Progression to CKD was 41.4 vs. 2.9% in NS patients (p < 0.001). Using the Cox
      model, only uCD80 excretion (p = 0.013, relative risk 6.171) predicted
      progression to CKD. CONCLUSIONS: Urinary CD80 predicts progression and remission
      in children with NS. The use of uCD80 as a prognostic marker facilitates the
      identification of high-risk patients at an early stage and may lead to better
      treatment selection.

PMID- 29569192
TI  - Differences in Symptom Severity and Independent Living Skills Between Re
      hospitalized and Not Re-hospitalized Individuals with Schizophrenia: A
      Longitudinal Study.
AB  - This study determined if schizophrenia symptom severity and independent living
      skills at discharge, or while residing in the community, predicted re
      hospitalization for discharged patients with schizophrenia. A total of 60
      patients were discharged from a state psychiatric hospital and had completed
      assessments at discharge, 6 months, and 1 year post discharge. There were 12
      patients who were re-hospitalized. There were no differences between the re
      hospitalized and not re-hospitalized groups based on third-party ratings of
      schizophrenia symptom severity and independent living skills. However, the
      patients' self-report and third party ratings of deteriorating general mental
      health symptoms 6 months after discharge predicted re-hospitalization.

PMID- 29569193
TI  - Detection of 2-aminoethylphosphonic acid in suspended particles in an
      ultraoligotrophic lake: a two-dimensional nuclear magnetic resonance (2D-NMR)
      study.
AB  - Particulate organic phosphorus (P) compounds were examined in ultraoligotrophic
      Lake Saiko, Japan. A cartridge filter was used to collect sufficient amount of
      suspended particles for analysis by a two-dimensional NMR (1H-31P heteronuclear
      multiple bond correlation). 2-Aminoethylphosphonic acid (2-AEP), a phosphonate,
      was detected in suspended particles in Lake Saiko. The identity of the
      phosphonate was confirmed by comparison with a commercially available compound.
      Because 2-AEP is bioavailable, microorganisms can store and use this compound
      under extremely P-limited conditions. This is the first study to detect 2-AEP in
      an ultra-oligotrophic environment.

PMID- 29569194
TI  - Hematological and histopathological effects of silver nanoparticles in rainbow
      trout (Oncorhynchus mykiss)-how about increase of salinity?
AB  - Hematological and histopathological toxicities of silver nanoparticles (Ag-NPs)
      to rainbow trout were assessed in three water salinities: 0.4 ppt (low salinity),
      6 +/- 0.3 ppt (moderate salinity), and 12 +/- 0.2 ppt (high salinity). The
      concentrations of Ag-NPs in the low salinity were 0.032, 0.1, 0.32, and 1 ppm,
      and in the moderate and high salinities were 3.2, 10, 32, and 100 ppm. The
      results indicated a concentration-dependently increased (thrombocyte, monocyte,
      and large lymphocyte) and decreased (neutrophil and small lymphocyte) white blood
      cell count in the Ag-NP treatments in the low salinity than the other ones in the
      moderate and high salinities. Red blood cell volume significantly increased in
      all of the experimental groups exposed to higher Ag-NP concentrations, especially
      those in the low salinity. In the moderate and high salinities, blood plasma
      total protein decreased in 10 and 32 ppm Ag-NP treatments, but albumin increased
      in the groups in the low salinity. Blood plasma ions (Cl-, Na+, K+, Ca2+, and
      Mg2+) showed high changes in the higher Ag-NP treatments. In all treatments, gill
      histological analysis demonstrated a time- and Ag-NP concentration-dependent
      extent of abnormalities, with the highest epithelial lifting in 1 ppm Ag-NPs in
      the low salinity and also the highest necrosis and aneurism in the 32 ppm
      treatments in other salinities. Lower Ag-NP concentrations in the low salinity
      led to fibrosis, villus fusion, inflammation, vacuolization, and microvillus
      hyperplasia in the gut, yet villi lifting and necrosis in 0.32 and 1 ppm of Ag
      NPs were the main anomalies. In addition to the mentioned alterations, villi
      abolitions predominantly occurred in 32 ppm Ag-NP concentrations in the moderate
      and high salinities. Overall, despite exposing to lower Ag-NP concentrations, the
      fish kept in the low salinity demonstrated more vulnerability to Ag-NPs than
      those in the other salinities.

PMID- 29569196
TI  - Environmental and human health issues related to pesticides: from usage and
      environmental fate to impact.

PMID- 29569195
TI  - Alterations of antioxidant indexes and inflammatory cytokine expression
      aggravated hepatocellular apoptosis through mitochondrial and death receptor
      dependent pathways in Gallus gallus exposed to arsenic and copper.
AB  - In this study, we sought to investigate the effects of sub-chronic exposure of
      arsenic (As) and copper (Cu) on oxidative stress, inflammatory response, and
      mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two
      1-day-old male Hy-line chickens were treated with basal diet, 30 mg/kg arsenic
      trioxide (As2O3), or/and 300 mg/kg copper sulfate (CuSO4) for 4, 8, and 12 weeks.
      Study revealed that exposure to As or/and Cu undermined the antioxidant function
      and increased lipid peroxidation. Worse yet, liver cell swollen, vacuolar
      degeneration, and inflammatory cell infiltration were accompanied by an increase
      of the nuclear factor-kappaB (NF-kappaB) and its downstream inflammation-related
      genes after exposure to As or/and Cu. Furthermore, mitochondria swollen and
      chromatin condensation were found in As and Cu groups, and hepatocyte nuclear
      membrane rupture and markedly increased (P < 0.01) apoptosis index were observed
      in As combined with Cu group. Meanwhile, the transcription and protein expression
      levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c), and
      caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated
      in As, Cu, and As + Cu groups in the liver tissues (P < 0.05, P < 0.01). Our
      results indicated that exposure to As or/and Cu could lead to oxidative stress,
      inflammatory response, and tissue damage and aggravate hepatocellular apoptosis
      through mitochondrial and death receptor-dependent pathways in chicken liver. And
      As and Cu showed a possible synergistic relationship in liver damage.

PMID- 29569197
TI  - Catalytic decomposition of PCDD/Fs on a V2O5-WO3/nano-TiO2 catalyst: effect of
      NaCl.
AB  - The effect of NaCl addition on the properties, activity, and deactivation of a
      V2O5-WO3/nano-TiO2 catalyst was investigated during catalytic decomposition of
      gas-phase polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans
      (PCDD/Fs). The extent of deactivation relates directly to the NaCl loading of the
      catalyst. Poisoning by sodium neutralizes acid sites, interacts strongly with
      active VOx species, and reduces the redox capacity of catalysts. In addition,
      NaCl is also a chlorine source and may actually accelerate the synthesis of new
      PCDD/Fs. Washing a catalyst with dilute sulfuric acid largely restores catalytic
      activity, breaking the interaction of Na+ ions and dispersed vanadia and removing
      Na from the catalyst surface. Consequently, catalyst acidity and redox capacity
      almost recover. Furthermore, sulfate residues react with surface adsorbed water
      to generate Bronsted acid sites, ensuing a surge of strong acidity of the
      catalysts.

PMID- 29569198
TI  - Performance modeling and valuation of snow-covered PV systems: examination of a
      simplified approach to decrease forecasting error.
AB  - The advent of modern solar energy technologies can improve the costs of energy
      consumption on a global, national, and regional level, ultimately spanning
      stakeholders from governmental entities to utility companies, corporations, and
      residential homeowners. For those stakeholders experiencing the four seasons,
      accurately accounting for snow-related energy losses is important for effectively
      predicting photovoltaic performance energy generation and valuation. This paper
      provides an examination of a new, simplified approach to decrease snow-related
      forecasting error, in comparison to current solar energy performance models. A
      new method is proposed to allow model designers, and ultimately users, the
      opportunity to better understand the return on investment for solar energy
      systems located in snowy environments. The new method is validated using two
      different sets of solar energy systems located near Green Bay, WI, USA: a 3.0-kW
      micro inverter system and a 13.2-kW central inverter system. Both systems were
      unobstructed, facing south, and set at a tilt of 26.56 degrees . Data were
      collected beginning in May 2014 (micro inverter system) and October 2014 (central
      inverter system), through January 2018. In comparison to reference industry
      standard solar energy prediction applications (PVWatts and PVsyst), the new
      method results in lower mean absolute percent errors per kilowatt hour of 0.039
      and 0.055%, respectively, for the micro inverter system and central inverter
      system. The statistical analysis provides support for incorporating this new
      method into freely available, online, up-to-date prediction applications, such as
      PVWatts and PVsyst.

PMID- 29569199
TI  - Effect of Cu(II) on the stability of oxyanion-substituted schwertmannite.
AB  - Schwertmannite, a Fe(III)-oxyhydroxysulfate mineral formed in acidic (pH 3~4),
      iron- and sulfate-rich acid mine drainage (AMD) environments, tends to undergo
      phase transformations with changes in pH and redox condition, which may depend on
      the presence of various trace anions and cations. In the present study, the
      effects of Cu(II) on the stability of arsenate-, chromate-, and molybdate
      substituted schwertmannite were investigated. The release of Fe(III) and sulfate
      from schwertmannite seems to be accelerated in the presence of Cu(II) at pH ~ 3,
      while Cu(II) retarded the dissolution of schwertmannite at pH ~ 5. XRD and SEM
      results showed that pure schwertmannite and chromate-substituted schwertmannite
      underwent transformation to goethite over a 2-month period, the presence of
      Cu(II) enhanced the stability of the mineral's structure at both pH 3 and 5.
      However, the structures of arsenate- and molybdate-substituted schwertmannites
      showed no significant changes in the presence or absence of Cu(II) at both pH 3
      and 5. During the phase transformation process, the amount of released oxyanions
      followed the sequence of chromate > molybdate > arsenate. Moreover, the release
      of arsenate and chromate from schwertmannite was retarded in the presence of
      Cu(II) at pH 5, whereas the release of molybdate was promoted. These results have
      important environmental implications for the stability of schwertmannite and its
      potential to immobilize contaminant trace elements under AMD conditions.

PMID- 29569200
TI  - Adaption and use of a quadcopter for targeted sampling of gaseous mercury in the
      atmosphere.
AB  - We modified a popular and inexpensive quadcopter to collect gaseous mercury (Hg)
      on gold-coated quartz cartridges, and analyzed the traps using cold vapor atomic
      fluorescence spectrometry. Flight times averaged 16 min, limited by battery life,
      and yielded > 5 pg of Hg, well above the limit of detection (< 0.2 pg). We
      measured progressively higher concentrations upon both vertical and lateral
      approaches to a dish containing elemental Hg, demonstrating that the method can
      detect Hg emissions from a point source. Using the quadcopter, we measured
      atmospheric Hg near anthropogenic emission sources in the mid-south USA,
      including a municipal landfill, coal-fired power plant (CFPP), and a petroleum
      refinery. Average concentrations (+/- standard deviation) immediately downwind of
      the landfill were higher at ground level and 30 m compared to 60 and 120 m (5.3
      +/- 0.5 ng m-3, 5.4 +/- 0.7 ng m-3, 4.2 +/- 0.7 ng m-3, and 2.5 +/- 0.3 ng m-3,
      respectively). Concentrations were also higher at an urban/industrial area
      (Memphis) (3.3 +/- 0.9 ng m-3) compared with a rural/background area (1.5 +/- 0.2
      ng m-3). Due to airspace flight restrictions near the CFPP and refinery, we were
      unable to access near-field (stack) plumes and did not observe differences
      between upwind and downwind locations. Overall, this study demonstrates that
      highly maneuverable multicopters can be used to probe Hg concentrations aloft,
      which may be particularly useful for evaluating Hg emissions from remote
      landscapes and transient sources that are inadequately characterized and leading
      to uncertainties in ecosystem budgets.

PMID- 29569201
TI  - Improved sorption of perfluorooctanoic acid on carbon nanotubes hybridized by
      metal oxide nanoparticles.
AB  - Multi-walled carbon nanotubes (MWCNTs) are often used as adsorbent because of
      their strong adsorption capacity. However, due to the nature of MWCNTs, their
      ability to adsorb perfluorooctanoic acid (PFOA), a highly hydrophobic pollutant,
      is low. In this study, MWCNTs were modified by three nano metal oxides (nano iron
      oxide, copper oxide, and zinc oxide). The pristine (as the control) and modified
      MWCNTs were characterized by BET-N2, TEM, FTIR, XPS, and XRD, which showed that
      nano metal oxides were well hybridized on the surface of MWCNTs. Radioactive
      labeled PFOA (14C-PFOA) was used to quantify it at trace level. Adsorption
      kinetics showed that intra-particle diffusion was the control step of PFOA
      adsorbing on metal oxides hybridized MWCNTs (MOHCNTs). Adsorption capacity of
      PFOA on the MOHCNTs was higher than that on the control due to electrostatic and
      hydrophobic interactions. In addition, PFOA formed inner-sphere complexes with
      metal oxide nanoparticles via ligand exchange. The alteration of PFOA adsorption
      capacity by increasing ionic strength was attributed to the aggregation degree of
      MWCNTs, electrostatic shielding, and/or salting out effect. The presence of Ca2+
      increased the adsorption, owing to not only its higher electrostatic shielding
      ability than Na+ but also its formation of bridge between PFOA and MOHCNTs. PFOA
      adsorption on MOHCNTs strongly depended on medium pH value. These results provide
      an innovative approach for removing trace PFOA from liquid medium.

PMID- 29569202
TI  - Concurrent removal of elemental mercury and SO2 from flue gas using a thiol
      impregnated CaCO3-based adsorbent: a full factorial design study.
AB  - Mercury (Hg) emitted from coal-based thermal power plants (CTPPs) can accumulate
      and bio-magnify in the food chain, thereby posing a risk to humans and wildlife.
      The central idea of this study was to develop an adsorbent which can concurrently
      remove elemental mercury (Hg0) and SO2 emitted from coal-based thermal power
      plants (CTPPs) in a single unit operation. Specifically, a composite adsorbent of
      CaCO3 impregnated with 2-mercaptobenimidazole (2-MBI) (referred to as modified
      calcium carbonate (MCC)) was developed. While 2-MBI having sulfur functional
      group could selectively adsorb Hg0, CaCO3 could remove SO2. Performance of the
      adsorbent was evaluated in terms of (i) removal (%) of Hg0 and SO2, (ii)
      adsorption mechanism, (iii) adsorption kinetics, and (iv) leaching potential of
      mercury from spent adsorbent. The adsorption studies were performed using a 22
      full factorial design of experiments with 15 ppbV of Hg0 and 600 ppmV of SO2. Two
      factors, (i) reaction temperature (80 and 120  degrees C; temperature range in
      flue gas) and (ii) mass of 2-MBI (10 and 15 wt%), were investigated for the
      removal of Hg0 and SO2 (as %). The maximum Hg0 and SO2 removal was 86 and 93%,
      respectively. The results of XPS characterization showed that chemisorption is
      the predominant mechanism of Hg0 and SO2 adsorption on MCC. The Hg0 adsorption on
      MCC followed Elovich kinetic model which is also indicative of chemisorption on
      heterogeneous surface. The toxicity characteristic leaching procedure (TCLP) and
      synthetic precipitation leaching procedure (SPLP) leached mercury from the spent
      adsorbent were within the acceptable levels defined in these tests. The
      engineering significance of this study is that the 2-MBI-modified CaCO3-based
      adsorbent has potential for concurrent removal of Hg0 and SO2 in a single unit
      operation. With only minor process modifications, the newly developed adsorbent
      can replace CaCO3 in the flue-gas desulfurization (FGD) system.

PMID- 29569204
TI  - Highly cited articles in wind tunnel-related research: a bibliometric analysis.
AB  - Wind tunnels have been widely employed in aerodynamic research. To characterize
      the high impact research, a bibliometric analysis was conducted on highly cited
      articles related to wind tunnel based on the Science Citation Index Expanded (SCI
      EXPANDED) database from 1900 to 2014. Articles with at least 100 citations from
      the Web of Science Core Collection were selected and analyzed in terms of
      publication years, authors, institutions, countries/territories, journals, Web of
      Science categories, and citation life cycles. The results show that a total of 77
      highly cited articles in 37 journals were published between 1959 and 2008.
      Journal of Fluid Mechanics published the most of highly cited articles. The USA
      was the most productive country and most frequent partner of internationally
      collaboration. The prolific institutions were mainly located in the USA and UK.
      The authors who were both first author and corresponding author published 88% of
      the articles. The Y index was also deployed to evaluate the publication
      characteristics of authors. Moreover, the articles with high citations in both
      history and the latest year with their citation life cycles were examined to
      provide insights for high impact research. The highly cited articles were almost
      earliest wind tunnel experimental data and reports on their own research
      specialty, and thus attracted high citations. It was revealed that classic works
      of wind tunnel research was frequently occurred in 1990s but much less in 2000s,
      probably due to the development of numerical models of computational fluid
      dynamic (CFD) in recent decades.

PMID- 29569203
TI  - Mancozeb exposure results in manganese accumulation and Nrf2-related antioxidant
      responses in the brain of common carp Cyprinus carpio.
AB  - Manganese (Mn)-containing dithiocarbamates such as Mancozeb (MZ) have been shown
      to induce oxidative stress-related toxicity in rodents and humans. However,
      little is known about the neurotoxic effects induced by MZ in fish. In this
      study, carp (Cyprinus carpio) were exposed to non-lethal waterborne
      concentrations of MZ, and oxidative stress parameters as well as metal
      accumulation in fish brains were evaluated. The experimental groups were as
      follows: control, MZ 5 mg/L, and MZ 10 mg/L. Fish were exposed for 7 days, and
      then brain was removed and prepared for subsequent analysis of antioxidant
      enzymes, reactive oxygen species (ROS), and expression of Nrf2 and phosphoNrf2.
      In parallel, manganese (Mn) levels were evaluated in blood and brain tissues. Mn
      levels were significantly increased in blood and brain of MZ-exposed carps. In
      addition, a concentration-dependent increase (p < 0.05) in ROS levels was
      observed in parallel to increments (p < 0.05) in the activity of major
      antioxidant enzymes, such as GPx, GR, and GST. On the other hand, significant
      decreases (p < 0.05) in CAT and SOD activities were observed. The expression of
      total and phosphorylated forms of Nrf2 was significantly (p < 0.05) upregulated
      in the brain of carps exposed to Mz when compared to the control, indicating an
      activation of the Nrf2 antioxidant pathway. Our study showed for the first time
      the activation of the Nrf2/ARE pathway and bioaccumulation of Mn induced by MZ
      exposure in fish species, highlighting important mechanisms of action and its
      toxicological impacts to aquatic organisms.

PMID- 29569205
TI  - The relationship between urban form and air pollution depends on seasonality and
      city size.
AB  - Understanding how urban form is related to air pollution is important to urban
      planning and sustainability, but the urban form-air pollution relationship is
      currently muddled by inconsistent findings. In this study, we investigated how
      the compositional and configurational attributes of urban form were related to
      different air pollution measures (PM2.5, API, and exceedance) in 83 Chinese
      cities, with explicit consideration of city size and seasonality. Ten landscape
      metrics were selected to quantify urban form attributes, and Spearman's
      correlation was used to quantify the urban form-air pollution relationship. Our
      results show that the urban form and air pollution relationship was dominated by
      city size and moderated by seasonality. Specifically, urban air pollution levels
      increased consistently and substantially from small to medium, large, and
      megacities. The urban form-air pollution relationship depended greatly on
      seasonality and monsoons. That is, the relationship was more pronounced in spring
      and summer than fall and winter, as well as in cities affected by monsoons. Urban
      air pollution was correlated more strongly with landscape composition metrics
      than landscape configuration metrics which seemed to affect only PM2.5
      concentrations. Our study suggests that, to understand how air pollution levels
      are related to urban form, city size and seasonality must be explicitly
      considered (or controlled). Also, in order to mitigate urban air pollution
      problems, regional urban planning is needed to curb the spatial extent of built
      up areas, reduce the degree of urban fragmentation, and increase urban
      compactness and contiguity, especially for large and megacities.

PMID- 29569206
TI  - Incidences of mortality of Indian peafowl Pavo cristatus due to pesticide
      poisoning in India and accumulation pattern of chlorinated pesticides in tissues
      of the same species collected from Ahmedabad and Coimbatore.
AB  - Incidences of mortality of Indian peafowl Pavo cristatus, the national bird
      (Schedule I Indian Wild Life Protection Act 1972), are rampant in India. Between
      January 2011 and March 2017, around 550 peafowl in 35 incidences were reported
      dead across the country. Due to the non-availability of fresh carcases, poisoning
      could not be confirmed. Birds which died due to kite string injuries in Ahmedabad
      (15) and accidents in Coimbatore (5) were tested for residues of chlorinated
      pesticides, namely hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane
      (DDT), endosulfan, heptachlor, dicofol, dieldrin and cholipyrifos. The liver,
      kidney and muscle were the tissues considered to document pesticide load. Total
      load ranged from BDL to 388.2 ng/g. DDT (95%) and HCH (80%) were detected more
      frequently. DDT (40%) and endosulfan (26%) contributed maximum to the total
      pesticide load followed by HCH (21%). Pesticide accumulation pattern among the
      organs was in the order of liver (123.9 ng/g) > kidney (91.9 ng/g) > muscle (19.5
      ng/g) with significant difference (p < 0.05). Peafowl from Ahmedabad had
      significantly (p < 0.05) higher level of total pesticide (149.0 ng/g) than birds
      from Coimbatore (47.8 ng/g). Although varying levels of chlorinated pesticide
      were detected, they were below reported toxic limits. Nevertheless, persistence
      of chlorinated pesticides and poisoning due to modern pesticides across the
      entire distribution range of Peafowl in India is a cause for concern.

PMID- 29569207
TI  - A brave new world.
AB  - Whereas up to 1950s the two major activities of academic Pathology-diagnostic and
      experimental-were both practiced by a single individual, thereafter, scientific,
      academic and economic factors created the conditions that favored monothematic
      practitioners. In this white paper, I argue that now, at the beginning of the
      21st century, this separation is detrimental to the discipline, and I propose
      changes that would reunite the two strands.

PMID- 29569208
TI  - Melanoma and Immune Checkpoint Inhibitors.
AB  - PURPOSE OF REVIEW: Prognosis of patients with advanced melanoma is dismal with a
      median overall survival of about 8 months and 5-year overall survival from a
      diagnosis of metastatic disease of roughly 10%. However, immune checkpoint
      inhibitors have brought indispensable benefits to melanoma patients. Here we will
      review the recent clinical efficacy and adverse events of immune checkpoint
      inhibitors for melanoma patients. RECENT FINDINGS: The immune checkpoint
      inhibitors increase confirmed objective response and prolong progression-free and
      overall survival of the afflicted patients in association with maintaining their
      quality of life. Although diverse immune-related adverse events occur, most of
      them are manageable by appropriate immunomodulating agents. Clinical efficacy of
      immune checkpoint inhibitors continues even after discontinuation of drugs.
      Compared with conventional therapeutic options, the immune checkpoint inhibitors
      appear to prolong the survival of patients with advanced melanoma. Further
      clinical trials are warranted to determine whether their combinatory use with
      other treatment options may augment benefits or not.

PMID- 29569209
TI  - Rejoinder to Letters to the Editor: Luke Wilkinson and Donald McLean, in response
      to Giovanni Bibbo's letter to the editor: Standardisation of shielding of medical
      X-ray installations.

PMID- 29569210
TI  - A simulation study comparing nine mathematical models of arterial input function
      for dynamic contrast enhanced MRI to the Parker model.
AB  - Due to large inter- and intra-patient variabilities of arterial input functions
      (AIFs), accurately modeling and using patient-specific AIF are very important for
      quantitative analysis of dynamic contrast enhanced MRI. Computer simulations were
      performed to evaluate and compare nine population AIF models with the Parker AIF
      used as 'gold standard'. The Parker AIF was calculated with a temporal resolution
      of 1.5 s, and then the other nine AIF models were used to fit the Parker AIF. A
      total of 100 randomly generated volume transfer constants (Ktrans) and
      distribution volumes (ve) were used to calculate the contrast agent concentration
      curves based on the Parker AIF and the extended Tofts model with blood plasma
      volume (vp) = 0.0, 0.01, 0.05 and 0.10. Subsequently, nine AIF models were used
      to fit these curves to extract physiological parameters (Ktrans, ve and vp). The
      agreements between generated and extracted Ktrans and ve values were evaluated
      using Bland-Altman analysis. The effects of the second pass of the Parker AIF
      model with and without adding Rician noise on extracted physiological parameters
      were evaluated by 1000 simulations using one of the nine mathematical AIF models
      closest to the Parker model with the smallest number of parameters. The results
      demonstrated that a six-parameter linear function plus bi-exponential function
      AIF model was almost equivalent to the Parker AIF and that the corresponding
      generated and extracted Ktrans and ve were in excellent agreements. The effects
      of the second pass of contrast agent circulation were small on extracted
      physiological parameters using the extended Tofts model, unless noise was added
      with signal to noise ratio less than 10 dB.

PMID- 29569211
TI  - Recommendations for urological follow-up of patients with neurogenic bladder
      secondary to spinal cord injury.
AB  - PURPOSE: To review currently available guidelines and recommendations regarding
      urological follow-up of patients after spinal cord injury (SCI) and present an
      evidence-based summary to support clinicians in their clinical practice. METHODS:
      Maximum data were collected according to different methods, including searches
      with multiple and specific keywords, reference checks, gray literature searches
      (congress reports, working papers, statement documents), and browsing-related Web
      site access. Obtained data were analyzed with the modified version of the Oxford
      grading system for recommendations using levels of evidence (LE) and grades of
      recommendation (GR). RESULTS: Different surveillance strategies exist, but there
      is no consensus among authors and organizations. As a result, practice patterns
      vary around the world. The present review indicates that proper urological follow
      up of SCI patients should consist of medical history (LE 1-4, GR B-C), clinical
      examination (LE 4, GR C), renal laboratory tests (LE 1-3, GR B), imaging
      surveillance of the upper urinary tract (LE 1-3, GR A-B), urodynamic study (LE 2
      4, GR B-C), and cystoscopy/cytology (LE 1-4, GR D). Clinicians agree that SCI
      patients should be followed up regularly with an individually tailored approach.
      A 1-year follow-up schedule seems reasonable in SCI patients without additional
      risk factors of renal deterioration (LE 3-4, GR C). In those who manifest risk
      factors, report changes in bladder behavior, or present with already developed
      complications of neurogenic bladder dysfunction, follow-up plans should be
      modified with more frequent checkups (LE 4, GR C). Urodynamic study should be
      repeated and considered as a routine monitoring strategy. CONCLUSION: Individuals
      with neurogenic lower urinary tract dysfunction are at increased risk of multiple
      complications. Nevertheless, proper follow-up after SCI improves the prognosis
      for these patients and their quality of life.

PMID- 29569212
TI  - Effect of pregnancy on cooling tone and rhythmic contractions of the rat urinary
      bladder.
AB  - OBJECTIVES: Pregnancy is a physiological alteration that can affect urinary
      bladder. Cooling of urinary bladder smooth muscle is known as a potent stimulus
      to micturition due to an increase in muscle tone. The current study investigates
      the effects of pregnancy on cooling tone and on the rhythmic contractions of the
      urinary bladder. METHODS: Twenty-four rats were used in this study as control
      group (non-pregnant) and pregnant group (18-20-day pregnancy). Isolated rat
      urinary muscle strips were suspended in organ baths containing Krebs' solution
      for isometric tension recording. RESULTS: Cooling from 37 to 5  degrees C induced
      a rapid and reproducible increase in basal tone, proportional to cooling
      temperature. Cooling also increased the rhythmic activity (amplitude and
      frequency) at 30 and 25  degrees C, then decreased at 20  degrees C, and
      abolished at 15-5  degrees C. These responses were more pronounced in pregnant
      group than in control group. Rhythmic contractions were abolished in calcium
      free, EGTA (1 mM)-containing Krebs' solution and in the presence of nifedipine,
      while they were not affected by CPA or TTX in both groups. Our investigation
      showed that the influx of extracellular calcium is important in inducing the
      rhythmic contractions. CONCLUSIONS: Pregnancy increases cooling-induced
      contraction in pregnant rat urinary preparations and its rhythmic contractions
      including amplitude and frequency than non-pregnant rat. Rhythmic contractions
      are myogenic in nature and highly extracellular calcium dependent. They may play
      a crucial role in urinary bladder overactivity and incontinence during pregnancy.

PMID- 29569214
TI  - ESR paper on the proper use of mobile devices in radiology.
AB  - : Mobile devices (smartphones, tablets, etc.) have become key methods of
      communication, data access and data sharing for the population in the past
      decade. The technological capabilities of these devices have expanded very
      rapidly; for example, their in-built cameras have largely replaced conventional
      cameras. Their processing power is often sufficient to handle the large data sets
      of radiology studies and to manipulate images and studies directly on hand-held
      devices. Thus, they can be used to transmit and view radiology studies, often in
      locations remote from the source of the imaging data. They are not recommended
      for primary interpretation of radiology studies, but they facilitate sharing of
      studies for second opinions, viewing of studies and reports by clinicians at the
      bedside, etc. Other potential applications include remote participation in
      educational activity (e.g. webinars) and consultation of online educational
      content, e-books, journals and reference sources. Social-networking applications
      can be used for exchanging professional information and teaching. Users of mobile
      device must be aware of the vulnerabilities and dangers of their use, in
      particular regarding the potential for inappropriate sharing of confidential
      patient information, and must take appropriate steps to protect confidential
      data. KEY POINTS: * Mobile devices have revolutionized communication in the past
      decade, and are now ubiquitous. * Mobile devices have sufficient processing power
      to manipulate and display large data sets of radiological images. * Mobile
      devices allow transmission & sharing of radiologic studies for purposes of second
      opinions, bedside review of images, teaching, etc. * Mobile devices are currently
      not recommended as tools for primary interpretation of radiologic studies. * The
      use of mobile devices for image and data transmission carries risks, especially
      regarding confidentiality, which must be considered.

PMID- 29569213
TI  - Prevalence, pathophysiological mechanisms and factors affecting urolithiasis.
AB  - The formation of urinary stone, urolithiasis, is one the oldest known disease
      affecting human throughout different civilizations and times. The exact
      pathophysiological mechanism of urolithiasis is not yet clear, as these calculi
      are of various types and too complex for simple understanding. A single theory
      cannot explain its formation; therefore, different theories are presented in
      various times for its explanation like free particle, fixed particle, Randall's
      plaque theory. In addition, various factors and components are identified that
      play an important role in the formation of these urinary calculi. In this review,
      composition of kidney stones, its prevalence/incidence, explanation of
      pathophysiological mechanisms and role of various factors; urinary pH, uric acid,
      parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin,
      matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm
      Horsfall protein, inter-alpha-inhibitors, have been discussed in detail.

PMID- 29569215
TI  - ABCs of the degenerative spine.
AB  - : Degenerative changes in the spine have high medical and socioeconomic
      significance. Imaging of the degenerative spine is a frequent challenge in
      radiology. The pathogenesis of this degenerative process represents a
      biomechanically related continuum of alterations, which can be identified with
      different imaging modalities. The aim of this article is to review radiological
      findings involving the intervertebral discs, end plates, bone marrow changes,
      facet joints and the spinal canal in relation to the pathogenesis of degenerative
      changes in the spine. Findings are described in association with the clinical
      symptoms they may cause, with a brief review of the possible treatment options.
      The article provides an illustrated review on the topic for radiology residents.
      TEACHING POINTS: * The adjacent vertebrae, intervertebral disc, ligaments and
      facet joints constitute a spinal unit. * Degenerative change is a response to
      insults, such as mechanical or metabolic injury. * Spine degeneration is a
      biomechanically related continuum of alterations evolving over time.

PMID- 29569216
TI  - Focal breast lesion characterization according to the BI-RADS US lexicon: role of
      a computer-aided decision-making support.

PMID- 29569217
TI  - MRI evaluation of peripheral vascular anomalies using time-resolved imaging of
      contrast kinetics (TRICKS) sequence.
AB  - INTRODUCTION: We describe the use of time-resolved imaging of contrast kinetics
      (TRICKS) sequence in the diagnosis of Peripheral Vascular Anomalies. In case of
      suspected vascular malformations time-resolved MR angiography might add important
      information for therapeutic decisions and follow-up. OBJECTIVE: The objective of
      our study was to assess the usefulness and diagnostic performance of time
      resolved imaging of contrast kinetics sequence in the evaluation of peripheral
      vascular anomalies. SUBJECTS AND METHODS: Sixty-six patients (23 pediatric, 43
      adult; mean age 26) affected by upper or lower limb vascular anomalies and
      studied using time-resolved imaging of contrast kinetics sequence were
      prospectively evaluated. All studies were performed on a 1.5-T whole-body MR
      system. Two independent readers tried to categorized the suspected vascular
      anomalies in pre-contrast and post-contrast MR sequences and assessed the overall
      TRICKS image quality. In 11 patients, the diagnostic performance comparability
      between TRICKS sequence and digital subtraction angiography was evaluated.
      RESULTS: On the basis of time-resolved imaging of contrast kinetics, 31 of the
      vascular anomalies were classified as high-flow vascular malformations, 29 as low
      flow vascular lesions and 6 as hemangiomas. There was no significant difference
      in image quality evaluation and vascular anomaly classification between the two
      observers. The vascular anomalies characteristics provided by moderate, good or
      excellent quality TRICKS images were confirmed by digital subtraction
      angiography. CONCLUSION: Time-resolved imaging of contrast kinetics sequence let
      the radiologist to acquire useful temporal information to correctly evaluate
      vascular anomalies components, adding more data to those provided by conventional
      MR sequences, especially in case of arteriovenous malformation. Therefore, both
      in pediatric and adult population, TRICKS could be used as an additional initial
      diagnostic tool to rightly classify these lesions and evaluate if a treatment is
      needed and which.

PMID- 29569218
TI  - CT features of diffuse lung disease in infancy.
AB  - Diffuse lung disease in infancy includes a wide range of very rare and peculiar
      pulmonary conditions usually not seen in older children, in whom diffuse lung
      disease has much greater overlap with adult disorders. The acronym chILD
      (childhood Interstitial Lung Disease) commonly defines these disorders, although
      air spaces, airways, alveolar epithelium, vasculature, pleura, and pleural spaces
      can also be involved, besides the pulmonary interstitium. chILD can be caused by
      diffuse developmental disorders, alveolar growth abnormalities, surfactant
      dysfunction disorders, and other specific conditions of poorly understood
      etiology. Chest CT imaging studies play a pivotal role in the evaluation of
      chILD. In some conditions CT findings can be specific, and thus make it possible
      avoiding further testing. In other disorders, findings are nonspecific, although
      they may suggest a diagnostic pattern and guide further testing. Nevertheless,
      chILD disorders often remain unrecognized on imaging studies, as they are very
      rare. The aim of this article is to review the CT patterns of lung involvement in
      a series of infants with chILD.

PMID- 29569219
TI  - Dopamine D2 agonist affects visuospatial working memory distractor interference
      depending on individual differences in baseline working memory span.
AB  - The interplay of dopaminergic striatal D1-D2 circuits is thought to support
      working memory (WM) by selectively filtering information that is to be remembered
      versus information to be ignored. To test this theory, we conducted an experiment
      in which healthy participants performed a visuospatial working memory (VSWM) task
      after ingesting the D2-receptor agonist cabergoline (or placebo), in a
      randomized, double-blinded, crossover design. Results showed greater interference
      from distractors under cabergoline, particularly for individuals with higher
      baseline dopamine (indicated by WM span). These findings support computational
      theories of striatal D1-D2 function during WM encoding and distractor-filtering,
      and provide new evidence for interactive cortico-striatal systems that support
      VSWM capacity and their dependence on WM span.

PMID- 29569220
TI  - Quantification of terpene trilactones in Ginkgo biloba with a 1H NMR method.
AB  - Ginkgo biloba L. has been used as a herbal medicine in the traditional treatment
      of insufficient blood flow, memory deficits, and cerebral insufficiency. The
      terpene trilactone components, the bioactive agents of Ginkgo biloba L., have
      also been reported to exhibit useful functionality such as anti-inflammatory and
      neuroprotective effects. Therefore, in the present research, we attempted to
      analyze quantitatively the terpene trilactone components in Ginkgo biloba leaf
      extract, with quantitative 1H NMR (qNMR) and obtained almost identical results to
      data reported using HPLC. Application of the qNMR method for the analysis of the
      terpene trilactone contents in commercial Ginkgo extract products, such as soft
      gel capsules and tablets, produced the same levels noted in package labels. Thus,
      qNMR is an alternative method for quantification of the terpene trilactone
      components in commercial Ginkgo extract products.

PMID- 29569221
TI  - Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl
      /water secretion that involves cAMP-dependent activation of CFTR.
AB  - Constipation is a common symptom frequently compromising the quality of daily
      life. Several mechanistically different drugs have been used to mitigate
      constipation, including Japanese herbal (Kampo) medicines. However, the
      mechanisms of their actions are often not well understood. Here we aimed to
      investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a
      Kampo medicine empirically prescribed for chronic constipation. Cl- channel
      activity was measured by the patch-clamp method in human cystic fibrosis
      transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human
      intestinal Caco-2 cells. cAMP was measured by a luciferase-based assay. Cell
      volume change was measured by a particle-sizing and particle-counting analyzer
      and video-microscopic measurement. In both CFTR-expressing HEK293T and Caco-2
      cells, JCT dose-dependently induced whole-cell currents showing typical
      biophysical and pharmacological features of CFTR. Robust expression of CFTR was
      confirmed by RT-PCR and Western blotting in Caco-2 cells. Luciferase-based
      measurement revealed that JCT increases intracellular cAMP levels. Administration
      of the adenylate cyclase inhibitor SQ22536 or CFTR inhibitor-172, or treatment
      with small interfering RNAs (siRNA) targeting CFTR, abolished JCT-induced whole
      cell currents, suggesting that elevated intracellular cAMP by JCT causes
      activation of CFTR in Caco-2 cells. Finally, blockade of CFTR activity by CFTR
      inhibitor-172 or siRNA-knockdown of CFTR or application of SQ22536 markedly
      reduced the degree of cell volume decrease induced by JCT. JCT can induce a Cl-
      efflux through the CFTR channel to promote water secretion, and this effect is
      likely mediated by increased cAMP production.

PMID- 29569222
TI  - Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge, Clathria
      prolifera.
AB  - Marine organisms such as marine sponges and soft corals are valuable sources of
      pharmacologically active secondary metabolites. In our ongoing research on the
      discovery of new secondary metabolites from marine organisms, two new pyrrolo-2
      aminoimidazoles, clathriroles A (1) and B (2), were isolated from the water
      soluble portion prepared from the methanol and acetone (2:1) extract of the
      marine sponge, Clathria prolifera, collected in Myanmar. The chemical structures
      of the isolated compounds were determined using extensive spectroscopic
      techniques, including NMR, HRESIMS, IR, and optical rotation, and comparisons
      with the reported literature. The spectroscopic analyses of 1 and 2 suggested
      that 1 is an enantiomer of antifungal N-methylmanzacidin C isolated from the
      marine sponge Axinella brevistyla, whereas 2 is a diastereomer of manzacidin D at
      C-11 isolated from the marine sponge Astrosclera willeyana. To the best of our
      knowledge, this is the first report of the isolation of the pyrrolo-2
      aminoimidazole compounds from C. prolifera. Furthermore, in contrast to the
      potency of N-methylmanzacidin C against Saccharomyces cerevisiae, the antifungal
      assay revealed that 1 and 2 lack any activity against this strain. Thus, these
      observations may suggest that the absolute configurations at both C-9 and C-11
      play an important role in controlling the antifungal activity of this type of
      compound.

PMID- 29569224
TI  - Author Correction: Clinical Benefit of Basal Insulin Analogue Treatment in
      Persons with Type 2 Diabetes Inadequately Controlled on Prior Insulin Therapy: A
      Prospective, Noninterventional, Multicenter Study.
AB  - In the original publication, values of the doses of insulin glargine, the most
      commonly used basal insulin analogue under the 'Discussion' section was
      incorrectly published.

PMID- 29569223
TI  - Appetite-enhancing effects of vanilla flavours such as vanillin.
AB  - Vanilla flavour is familiar to consumers through foods, cosmetics, household
      products and some medicines. Vanilla flavouring agents typically contain vanillin
      or its analogue ethyl vanillin. Our previous study revealed that the inhalation
      of eugenol, which contains a vanillyl group, has an appetite-enhancing effect,
      and the inhalation of aroma compounds containing the vanillyl group or its
      analogues led to increased food intake in mice. Here, we found that vanillin,
      ethyl vanillin and eugenol showed appetite-enhancing effects, whereas isoeugenol
      and safrole did not. These results suggest that the appetite-enhancing effects
      could be attributable to the vanillyl group and could be affected by the position
      of the double bond in the aliphatic chain. Furthermore, the results of
      intraperitoneal administration of eugenol and vanillin suggest that their
      appetite-enhancing effects could occur via stimulation of olfactory receptors.

PMID- 29569225
TI  - A statistical model for helices with applications.
AB  - Motivated by a cutting edge problem related to the shape of <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>alpha</mml:mi></mml:math> 
      helices in proteins, we formulate a parametric statistical model, which
      incorporates the cylindrical nature of the helix. Our focus is to detect a
      "kink," which is a drastic change in the axial direction of the helix. We propose
      a statistical model for the straight <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>alpha</mml:mi></mml:math> 
      helix and derive the maximum likelihood estimation procedure. The cylinder is an
      accepted geometric model for <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>alpha</mml:mi></mml:math> 
      helices, but our statistical formulation, for the first time, quantifies the
      uncertainty in atom positions around the cylinder. We propose a change point
      technique "Kink-Detector" to detect a kink location along the helix. Unlike
      classical change point problems, the change in direction of a helix depends on a
      simultaneous shift of multiple data points rather than a single data point, and
      is less straightforward. Our biological building block is crowdsourced data on
      straight and kinked helices; which has set a gold standard. We use this data to
      identify salient features to construct Kink-detector, test its performance and
      gain some insights. We find the performance of Kink-detector comparable to its
      computational competitor called "Kink-Finder." We highlight that identification
      of kinks by visual assessment can have limitations and Kink-detector may help in
      such cases. Further, an analysis of crowdsourced curved <mml:math
      xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>alpha</mml:mi></mml:math> 
      helices finds that Kink-detector is also effective in detecting moderate changes
      in axial directions.

PMID- 29569227
TI  - Clinical and dermoscopic features of Spitz naevus by sex, age and anatomical
      site: a study of 913 Spitz naevi.

PMID- 29569226
TI  - Inherited pulmonary cylindromas: extending the phenotype of CYLD mutation
      carriers.
AB  - BACKGROUND: Germline mutations in the tumour suppressor gene CYLD are recognized
      to be associated with the development of multiple cutaneous cylindromas. We
      encountered such a patient who presented with breathlessness because of multiple
      pulmonary cylindromas. OBJECTIVES: To search for clinical and radiological
      features of multiple pulmonary cylindromas in a cohort of 16 patients with CYLD
      mutations. METHODS: A retrospective case-note review was carried out in a
      tertiary dermatogenetics clinic where CYLD mutation carriers are reviewed on an
      annual basis. In-depth investigation was carried out for patients with pulmonary
      tumours. RESULTS: Four patients had radiological imaging of their lungs, of which
      two had multiple pulmonary cylindromas that were confirmed histologically. Serial
      computed tomography monitoring allowed for pre-emptive endobronchial laser
      ablation, preventing major airway obstruction and pulmonary collapse.
      CONCLUSIONS: Pulmonary cylindromas are an unrecognized, but infrequently
      symptomatic, aspect of the phenotype in these patients that can have implications
      for patient care. They should be considered in patients with a high tumour burden
      that present with respiratory symptoms, and where appropriate, monitored with
      serial imaging.

PMID- 29569228
TI  - Model-averaged confounder adjustment for estimating multivariate exposure effects
      with linear regression.
AB  - In environmental and nutritional epidemiology and in many other fields, there is
      increasing interest in estimating the effect of simultaneous exposure to several
      agents (e.g., multiple nutrients, pesticides, or air pollutants) on a health
      outcome. We consider estimating the effect of a multivariate exposure that
      includes several continuous agents and their interactions-on an outcome, when the
      true confounding variables are an unknown subset of a potentially large (relative
      to sample size) set of measured covariates. Our approach is rooted in the ideas
      of Bayesian model averaging: the exposure effect is estimated as a weighted
      average of the estimated exposure effects obtained under several linear
      regression models that include different sets of the potential confounders. We
      introduce a data-driven prior that assigns to the likely confounders a higher
      probability of being included into the regression model. We show that our
      approach can also be formulated as a penalized likelihood formulation with an
      interpretable tuning parameter. Through a simulation study, we demonstrate that
      the proposed approach identifies parsimonious models that are fully adjusted for
      observed confounding and estimates the multivariate exposure effect with smaller
      mean squared error compared to several alternatives. We apply the method to an
      Environmental Wide Association Study using National Heath and Nutrition
      Examination Survey to estimate the effect of mixtures of nutrients and pesticides
      on lipid levels.

PMID- 29569229
TI  - Diagnostic accuracy of dermatofluoroscopy in cutaneous melanoma detection:
      results of a prospective multicentre clinical study in 476 pigmented lesions.
AB  - BACKGROUND: Early detection is a key factor in improving survival from melanoma.
      Today, the clinical diagnosis of cutaneous melanoma is based mostly on visual
      inspection and dermoscopy. Preclinical studies in freshly excised or paraffin
      embedded tissue have shown that the melanin fluorescence spectra after stepwise
      two-photon excitation, a process termed dermatofluoroscopy, differ between
      cutaneous melanoma and melanocytic naevi. However, confirmation from a larger
      prospective clinical study is lacking. OBJECTIVES: The primary end point of this
      study was to determine the diagnostic accuracy of dermatofluoroscopy in melanoma
      detection. Secondary end points included the collection of data for improving the
      computer algorithm that classifies skin lesions based on melanin fluorescence and
      the assessment of safety aspects. METHODS: This was a prospective, blinded,
      multicentre clinical study in patients with pigmented skin lesions (PSLs)
      indicated for excision either to rule out or to confirm cutaneous melanoma. All
      included lesions underwent dermoscopy and dermatofluoroscopy in vivo before
      lesions were excised and subjected to histopathological examination. RESULTS: In
      total, 369 patients and 476 PSLs were included in the final analysis. In 101 of
      476 lesions (21.2%) histopathology revealed melanoma. The observed sensitivity of
      dermatofluoroscopy was 89.1% (90 of 101 melanomas identified), with an observed
      specificity of 44.8%. The positive and negative predictive values were 30.3% and
      93.9%, respectively. No adverse events occurred. CONCLUSIONS: Dermatofluoroscopy
      is a safe and accurate diagnostic method to aid physicians in diagnosing
      cutaneous melanoma. Limitations arise from largely amelanotic or regressing
      lesions lacking sufficient melanin fluorescence.

PMID- 29569230
TI  - Socioeconomic status and risk of intensive care unit admission with sepsis.
AB  - BACKGROUND: A recent study showed higher risk of bacteremia among individuals
      with low socioeconomic status (SES). We hypothesized that patients with a low SES
      have a higher risk of intensive care unit (ICU) admission with sepsis compared to
      patients with higher SES. METHODS: This was a case-control study on patients with
      sepsis admitted to the ICU at Aarhus University Hospital, Denmark (2008-2010).
      Three hundred eighty-three sepsis patients were matched on sex, age, and zip code
      with controls retrieved from the background population. SES was defined as
      highest accomplished educational level, yearly income, cohabitation status, and
      occupation. The odds ratio (OR) of being admitted with sepsis to the ICU was
      calculated using conditional logistic regression, adjusting for the Charlson
      Comorbidity Index and the remaining socioeconomic variables. RESULTS: The
      adjusted odds of being admitted to the ICU with sepsis were significantly higher
      among individuals living alone (OR 1.72, 95% confidence interval (CI) 1.33-2.24,
      P < 0.001) compared to individuals living with a cohabitant. Individuals outside
      the labor force had an adjusted OR of 3.50 (CI 2.36-5.18, P < 0.001) compared to
      individuals in the labor force. Individuals with a medium level of education had
      an increased risk of admission to the ICU with sepsis compared to a high level of
      education (adjusted OR 1.43, CI 1.02-2.00, P = 0.04). There was no significant
      association between income and risk of ICU admission with sepsis after
      adjustment. CONCLUSION: Individuals living alone, being outside the labor force,
      or having a medium level of education had significantly higher risk of ICU
      admission with sepsis.

PMID- 29569231
TI  - Economic evaluations of interventions for people with cerebral palsy:
      implications for future research.

PMID- 29569232
TI  - Prediction of responders to ketogenic diet based on syndrome and etiology:
      identification of a new target population?

PMID- 29569233
TI  - Statistical process control in healthcare improvement - new kid on the block?

PMID- 29569234
TI  - Negligible effect of competition on coral colony growth.
AB  - Competition is an important determinant of assemblage structure and population
      regulation, often resulting in decreased growth, fecundity or survival. In
      corals, most studies testing for an effect of competition on demographic traits,
      such as growth, have been experimental and often impose very high levels of
      competition upon colonies. To more realistically assess the role of competition
      on coral traits, multispecies studies in the wild are required. Here, we use 5 yr
      of data that includes 11 coral species on the reef crest at Lizard Island on the
      Great Barrier Reef to quantify the effect of competition on growth. Additionally,
      we test whether species differ in their susceptibility to direct-contact
      (overgrowth and digestion) and overtopping competition, and whether species from
      some morphological groups are more likely to compete with one another than with
      species from other morphological groups. We also investigate the relationships
      between competitive ability and three key traits: growth rate, mechanical
      stability and fecundity. In contrast to most previous work using field
      manipulations of competition, we found a negligible effect of competition on
      growth. Acropora species consistently won overtopping encounters but lost in
      direct-contact encounters, and these results were consistent among the four
      Acropora morphological groups. In contrast, the massive Goniastrea spp. were poor
      at overtopping but generally won direct-contact encounters. Only tabular colonies
      were disproportionally more likely to compete against one another than with other
      morphologies. This propensity increases intraspecific relative to interspecific
      competition, a phenomenon that can promote coexistence when it is present among
      dominant competitors. Good competitors grew more quickly and had higher fecundity
      but were less mechanically stable, implying a tradeoff between performance during
      disturbance vs. performance in the absence of disturbance. We conclude that
      competition among adults is less likely to influence community dynamics than
      previously thought. If competition does have an effect, it is more likely to
      occur at life-stages other than adults.

PMID- 29569235
TI  - Application of ERT, Saline Tracer and Numerical Studies to Delineate Preferential
      Paths in Fractured Granites.
AB  - Accurate quantification of in situ heterogeneity and flow processes through
      fractured geologic media remains elusive for hydrogeologists due to the
      complexity in fracture characterization and its multiscale behavior. In this
      research, we demonstrated the efficacy of tracer-electrical resistivity
      tomography (ERT) experiments combined with numerical simulations to characterize
      heterogeneity and delineate preferential flow paths in a fractured granite
      aquifer. A series of natural gradient saline tracer experiments were conducted
      from a depth window of 18 to 22 m in an injection well (IW) located inside the
      Indian Institute of Technology Hyderabad campus. Tracer migration was monitored
      in a time-lapse mode using two cross-sectional surface ERT profiles placed in the
      direction of flow gradient. ERT data quality was improved by considering
      stacking, reciprocal measurements, resolution indicators, and geophysical logs.
      Dynamic changes in subsurface electrical properties inferred via resistivity
      anomalies were used to highlight preferential flow paths of the study area.
      Temporal changes in electrical resistivity and tracer concentration were
      monitored along the vertical in an observation well located at 48 m to the east
      of the IW. ERT-derived tracer breakthrough curves were in agreement with
      geochemical sample measurements. Fracture geometry and hydraulic properties
      derived from ERT and pumping tests were further used to evaluate two mathematical
      conceptualizations that are relevant to fractured aquifers. Results of numerical
      analysis conclude that dual continuum model that combines matrix and fracture
      systems through a flow exchange term has outperformed equivalent continuum model
      in reproducing tracer concentrations at the monitoring wells (evident by a
      decrease in RMSE from 199 to 65 mg/L). A sensitivity analysis on model
      simulations conclude that spatial variability in hydraulic conductivity, local
      scale dispersion, and flow exchange at fracture-matrix interface have a profound
      effect on model simulations.

PMID- 29569236
TI  - Predicting ecosystem vulnerability to biodiversity loss from community
      composition.
AB  - Ecosystems vary widely in their responses to biodiversity change, with some
      losing function dramatically while others are highly resilient. However,
      generalizations about how species- and community-level properties determine these
      divergent ecosystem responses have been elusive because potential sources of
      variation (e.g., trophic structure, compensation, functional trait diversity) are
      rarely evaluated in conjunction. Ecosystem vulnerability, or the likely change in
      ecosystem function following biodiversity change, is influenced by two types of
      species traits: response traits that determine species' individual sensitivities
      to environmental change, and effect traits that determine a species' contribution
      to ecosystem function. Here we extend the response-effect trait framework to
      quantify ecosystem vulnerability and show how trophic structure, within-trait
      variance, and among-trait covariance affect ecosystem vulnerability by linking
      extinction order and functional compensation. Using in silico trait-based
      simulations we found that ecosystem vulnerability increased when response and
      effect traits positively covaried, but this increase was attenuated by decreasing
      trait variance. Contrary to expectations, in these communities, both functional
      diversity and trophic structure increased ecosystem vulnerability. In contrast,
      ecosystem functions were resilient when response and effect traits covaried
      negatively, and variance had a positive effect on resiliency. Our results suggest
      that although biodiversity loss is often associated with decreases in ecosystem
      functions, such effects are conditional on trophic structure, and the variation
      within and covariation among response and effect traits. Taken together, these
      three factors can predict when ecosystems are poised to lose or gain function
      with ongoing biodiversity change.

PMID- 29569237
TI  - Workforce participation and activities in Parkinson's disease patients receiving
      device-aided therapy.
AB  - OBJECTIVES: Many countries have an aging population, and it is thus likely that
      Parkinson's disease (PD) will become an increasing health problem. It is
      important to ensure this group can use their resources in the best way possible,
      including remaining in the work market. This study aimed to investigate workforce
      participation and daily activities among patients with PD receiving device-aided
      therapy to provide new knowledge that may be used to inform decisions about these
      therapy options. MATERIALS AND METHODS: This was a retrospective, descriptive
      quantitative pilot study, including 67 patients with PD from 3 centers in Sweden
      and Denmark. Included patients were younger than 67 years at the time of
      introduction of device-aided therapy. Eligible patients were identified by the
      Swedish national Parkinson patient registry or by the treating neurologist.
      Quantitative interviews were made by telephone. RESULTS: A majority of the
      patients could perform the same, or more, amount of activities approximately 5
      years after the introduction of device-aided therapy. A small number of patients
      receiving deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel
      (LCIG) were able to increase their work capacity within 1 year of initiating
      device-aided therapy and a remarkably high share could still work at the end
      point of this study, approximately 15 years since the diagnosis of PD.
      CONCLUSIONS: Device-aided therapy may sustain or increase daily activities and
      workforce participation in patients with PD who have not yet reached retirement
      age. There is need for prospective studies, both quantitative and qualitative, to
      confirm these results.

PMID- 29569238
TI  - Factor analysis and Mokken scaling of the Organizational Commitment Questionnaire
      in nurses.
AB  - AIMS: To generate an Arabic version of the Organizational Commitment
      Questionnaire that would be easily understood by Arabic speakers and would be
      sensitive to Arabic culture. BACKGROUND: The nursing workforce in Saudi Arabia is
      undergoing a process of Saudization but there is a need to understand the factors
      that will help to retain this workforce. INTRODUCTION: No organizational
      commitment tools exist in Arabic that are specifically designed for health
      organizations. An Arabic version of the organizational commitment tool could aid
      Arabic speaking employers to understand their employees' perceptions of their
      organizations. METHODS: Translation and back-translation followed by factor
      analysis (principal components analysis and confirmatory factor analysis) to test
      the factorial validity and item response theory (Mokken scaling). RESULTS: A two
      factor structure was obtained for the Organizational Commitment Questionnaire
      comprising Factor 1: Value commitment; and Factor 2: Commitment to stay with
      acceptable reliability measured by internal consistency. A Mokken scale was
      obtained including items from both factors showing a hierarchy of items running
      from commitment to the organization and commitment to self. DISCUSSION: This
      study shows that the Arabic version of the OCQ retained the established two
      factor structure of the original English-language version. Although the two
      factors - 'value commitment' and 'commitment to stay' - repudiate the original
      developers' single factor claim. CONCLUSION: A useful insight into the structure
      of the Organizational Commitment Questionnaire has been obtained with the novel
      addition of a hierarchical scale. IMPLICATIONS FOR NURSING POLICY: The
      Organizational Commitment Questionnaire is now ready to be used with nurses in
      the Arab speaking world and could be used a tool to measure the contemporary
      commitment of nursing employees and in future interventions aimed at increasing
      commitment and retention of valuable nursing staff.

PMID- 29569239
TI  - Integrating species traits into species pools.
AB  - Despite decades of research on the species-pool concept and the recent explosion
      of interest in trait-based frameworks in ecology and biogeography, surprisingly
      little is known about how spatial and temporal changes in species-pool functional
      diversity (SPFD) influence biodiversity and the processes underlying community
      assembly. Current trait-based frameworks focus primarily on community assembly
      from a static regional species pool, without considering how spatial or temporal
      variation in SPFD alters the relative importance of deterministic and stochastic
      assembly processes. Likewise, species-pool concepts primarily focus on how the
      number of species in the species pool influences local biodiversity. However,
      species pools with similar richness can vary substantially in functional-trait
      diversity, which can strongly influence community assembly and biodiversity
      responses to environmental change. Here, we integrate recent advances in
      community ecology, trait-based ecology, and biogeography to provide a more
      comprehensive framework that explicitly considers how variation in SPFD, among
      regions and within regions through time, influences the relative importance of
      community assembly processes and patterns of biodiversity. First, we provide a
      brief overview of the primary ecological and evolutionary processes that create
      differences in SPFD among regions and within regions through time. We then
      illustrate how SPFD may influence fundamental processes of local community
      assembly (dispersal, ecological drift, niche selection). Higher SPFD may increase
      the relative importance of deterministic community assembly when greater
      functional diversity in the species pool increases niche selection across
      environmental gradients. In contrast, lower SPFD may increase the relative
      importance of stochastic community assembly when high functional redundancy in
      the species pool increases the influence of dispersal history or ecological
      drift. Next, we outline experimental and observational approaches for testing the
      influence of SPFD on assembly processes and biodiversity. Finally, we highlight
      applications of this framework for restoration and conservation. This species
      pool functional diversity framework has the potential to advance our
      understanding of how local- and regional-scale processes jointly influence
      patterns of biodiversity across biogeographic regions, changes in biodiversity
      within regions over time, and restoration outcomes and conservation efforts in
      ecosystems altered by environmental change.

PMID- 29569240
TI  - From 'green' technologies to 'red' antioxidant compounds extraction of purple
      corn: a combined ultrasound-ultrafiltration-purification approach.
AB  - BACKGROUND: A pilot scale process consisting of ultrasound-assisted extraction,
      ammonium sulfate precipitation, cross-flow ultrafiltration and AB-8 macroporous
      resins purification aiming to recover anthocyanins and zein from purple corn (PC)
      was optimized and scaled-up. The effects of five independent variables (ethanol
      concentration, liquid to solid ratio, ultrasound temperature, time and power)
      were discussed and the most influential factors were optimized. RESULTS: The
      highest total anthocyanin (0.45 +/- 0.01 g kg-1 ) and zein (17.14 +/- 1.73 g kg-1
      ) contents from purple corn were obtained using an ultrasound power of 105 W, an
      extraction time of 90 min, an ethanol concentration of 74% and a liquid to solid
      ratio of 26:1, at 70  degrees C, and this was consistent with the predicted
      values (0.46 and 17.36 g kg-1 , for anthocyanin and zein, respectively).
      Subsequently, ammonium sulfate precipitation was used to isolate anthocyanins and
      zein. After cross-flow ultrafiltration, zein (6.30 g) was obtained with 80%
      purity. Anthocyanins were purified by AB-8 macroporous resins, resulting in 1.60
      g of anthocyanins. High-performance liquid chromatography-electrospray ionization
      mass spectrometry analysis revealed eight different anthocyanins in purple corn
      extracts. CONCLUSION: From the results obtained in the present study, it can be
      concluded that the proposed extraction-separation-filtration-purification method
      applied under the optimal conditions could be scaled-up to recover anthocyanins
      and zein simultaneously. Moreover, under the selected conditions, no significant
      degradation of anthocyanins was observed. (c) 2018 Society of Chemical Industry.

PMID- 29569241
TI  - Effects on bread and oil quality after functionalization with microencapsulated
      chia oil.
AB  - BACKGROUND: Omega-3 and omega-6 fatty acids-rich oils suffer oxidation reactions
      that alter their chemical and organoleptic quality. Microencapsulation can be a
      powerful tool for protection against ambient conditions. In the present study,
      the addition of microencapsulated chia oil as an ingredient in bread preparations
      and its effect on the technological and chemical quality of breads was
      investigated. RESULTS: Microencapsulation of chia oil was carried out by freeze
      drying with soy proteins as wall material and oil release was determined under in
      vitro gastric and intestinal conditions. Encapsulated oil-containing bread showed
      no differences in specific volume, average cell area, firmness and chewiness with
      respect to control bread. Unencapsulated oil-containing bread showed a marked
      increase in hydroperoxide values respect to control, whereas encapsulated oil
      containing bread values were not affected by baking and bread storage. The fatty
      acid profiles showed a decrease of 13% and 16%, respectively, in alpha-linolenic
      acid in the encapsulated and unencapsulated oils with respect to bulk chia oil.
      Sensory analysis showed no significant differences between bread samples.
      CONCLUSION: The addition of encapsulated chia oil did not alter the technological
      quality of breads and prevented the formation of hydroperoxide radicals. A ration
      of encapsulated oil-containing bread contributes 60% of the recommended dietary
      intake of omega-3 fatty acids. (c) 2018 Society of Chemical Industry.

PMID- 29569242
TI  - Egg-Yolk Sphingomyelin and Phosphatidylcholine Attenuate Cholesterol Absorption
      in Caco-2 Cells.
AB  - Phospholipids have been shown to modulate intestinal cholesterol absorption in
      cells and animals, a process that is regulated by several transporter proteins.
      Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this
      process. The mechanism by which phospholipids modulate cholesterol absorption
      remains unknown. Here, we evaluate the effects of egg-yolk phospholipids on
      cholesterol absorption and transport in human colon carcinoma cell line (Caco-2
      cells) and on the expression of NPC1L1 and others proteins associated with
      cholesterol absorption (ABCG5, ABCG8, ABCA1, ACAT2, MTP, CAV-1, ANX-2). The roles
      of SREBP-1 and SREBP-2 in this process were also investigated. The results show
      that egg-yolk sphingomyelin (CerPCho) and phosphatidylcholine (PtdCho) inhibit
      cholesterol transport in the Caco-2 monolayer in a dose-dependent manner. These
      might be due to the decrease of the cholesterol solubility in micelles as well as
      to the increases in the micellar sizes and the bile acid-binding capacity.
      Furthermore, the treatments with egg-yolk CerPCho or PtdCho at 1.2 mmol/L reduced
      the expression levels of NPC1L1 protein to 21 or 22%, respectively, and its mRNA
      to 9 or 31% of that in the control group (p < 0.05). Moreover, there was a
      general inhibitory effect of egg-yolk PtdCho and CerPCho on the mRNA levels of
      SREBP-1, and SREBP-2. These results suggest that the inhibitory effect of egg
      yolk CerPCho and PtdCho on cholesterol transport might be due to their
      interference with the physicochemical properties of micelles and their
      regulations on the expression of the NPC1L1 gene.

PMID- 29569243
TI  - Dietary High-Oleic Acid Soybean Oil Dose Dependently Attenuates Egg Yolk Content
      of n-3 Polyunsaturated Fatty Acids in Laying Hens Fed Supplemental Flaxseed Oil.
AB  - Chickens can hepatically synthesize eicosapentaenoic acid (20:5 n-3) and
      docosahexaenoic acid (22:6 n-3) from alpha-linolenic acid (ALA; 18:3 n-3);
      however, the process is inefficient and competitively inhibited by dietary
      linoleic acid (LNA; 18:2 n-6). In the present study, the influence of dietary
      high-oleic acid (OLA; 18:1 n-9) soybean oil (HOSO) on egg and tissue deposition
      of ALA and n-3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA
      was investigated in laying hens fed a reduced-LNA base diet supplemented with
      high-ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of
      LNA would promote greater hepatic conversion of ALA to very long-chain (VLC;
      >20C) n-3 PUFA, while supplemental dietary HOSO would simultaneously further
      enrich eggs with OLA without influencing egg n-3 PUFA contents. Nine 51-week-old
      hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each
      group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20
      to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total
      n-3 and VLC n-3 PUFA contents in egg yolk by 9.4-fold and 2.2-fold, respectively,
      while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of
      ALA, VLC n-3 PUFA, and total n-3 PUFA by 37, 15, and 32%, respectively. These
      results suggest that dietary OLA is not neutral with regard to the overall
      process by which dietary ALA is absorbed, metabolized, and deposited into egg
      yolk, either intact or in the form of longer-chain/more unsaturated n-3 PUFA
      derivatives.

PMID- 29569244
TI  - Maternal and perinatal outcomes in pregnant women with suspected Ebola virus
      disease in Sierra Leone, 2014.
AB  - OBJECTIVE: To describe maternal and perinatal outcomes among pregnant women with
      suspected Ebola virus disease (EVD) in Sierra Leone. METHODS: Observational
      investigation of maternal and perinatal outcomes among pregnant women with
      suspected EVD from five districts in Sierra Leone from June to December 2014.
      Suspected cases were ill pregnant women with symptoms suggestive of EVD or
      relevant exposures who were tested for EVD. Case frequencies and odds ratios were
      calculated to compare patient characteristics and outcomes by EVD status.
      RESULTS: There were 192 suspected cases: 67 (34.9%) EVD-positive, 118 (61.5%) EVD
      negative, and 7 (3.6%) EVD status unknown. Women with EVD had increased odds of
      death (OR 10.22; 95% CI, 4.87-21.46) and spontaneous abortion (OR 4.93; 95% CI,
      1.79-13.55) compared with those without EVD. Women without EVD had a high
      frequency of death (30.2%) and stillbirths (65.9%). One of 14 neonates born
      following EVD-negative and five of six neonates born following EVD-positive
      pregnancies died. CONCLUSION: EVD-positive and EVD-negative women with suspected
      EVD had poor outcomes, highlighting the need for increased attention and
      resources focused on maternal and perinatal health during an urgent public health
      response. Capturing pregnancy status in nationwide surveillance of EVD can help
      improve understanding of disease burden and design effective interventions.

PMID- 29569245
TI  - Contrasting drivers and trends of coniferous and deciduous tree growth in
      interior Alaska.
AB  - The boreal biome represents approximately one third of the world's forested area
      and plays an important role in global biogeochemical and energy cycles. Numerous
      studies in boreal Alaska have concluded that growth of black and white spruce is
      declining as a result of temperature-induced drought stress. The combined
      evidence of declining spruce growth and changes in the fire regime that favor
      establishment of deciduous tree species has led some investigators to suggest the
      region may be transitioning from dominance by spruce to dominance by deciduous
      forests and/or grasslands. Although spruce growth trends have been extensively
      investigated, few studies have evaluated long-term radial growth trends of the
      dominant deciduous species (Alaska paper birch and trembling aspen) and their
      sensitivity to moisture availability. We used a large and spatially extensive
      sample of tree cores from interior Alaska to compare long-term growth trends
      among contrasting tree species (white and black spruce vs. birch and aspen). All
      species showed a growth peak in the mid-1940s, although growth following the peak
      varied strongly across species. Following an initial decline from the peak,
      growth of white spruce showed little evidence of a trend, while black spruce and
      birch growth showed slight growth declines from ~1970 to present. Aspen growth
      was much more variable than the other species and showed a steep decline from
      ~1970 to present. Growth of birch, black and white spruce was sensitive to
      moisture availability throughout most of the tree-ring chronologies, as evidenced
      by negative correlations with air temperature and positive correlations with
      precipitation. However, a positive correlation between previous July
      precipitation and aspen growth disappeared in recent decades, corresponding with
      a rise in the population of the aspen leaf miner (Phyllocnistis populiella), an
      herbivorous moth, which may have driven growth to a level not seen since the
      early 20th century. Our results provide important historical context for recent
      growth and raise questions regarding competitive interactions among the dominant
      tree species and exchanges of carbon and energy in the warming climate of
      interior Alaska.

PMID- 29569247
TI  - Heparin-binding protein as a biomarker of post-injury sepsis in trauma patients.
AB  - BACKGROUND: Heparin-binding protein (HBP) is a neutrophil-derived protein
      advocated as a biomarker in sepsis. We evaluated plasma HBP as a predictor of
      post-injury sepsis in trauma patients. METHODS: Ninety-seven trauma patients were
      studied during the first week of intensive care. Injury-related data were
      collected and clinical parameters registered daily. Plasma HBP was sampled on day
      1, 3 and 5 after trauma and evaluated for associations with injury-related
      parameters and sepsis. The predictive properties of HBP were compared to C
      reactive protein (CRP) and white blood cell count (WBC). RESULTS: Median Injury
      Severity Score was 33, one-third of the trauma patients received massive
      transfusion and a quarter was in shock on arrival. Overall 30-day mortality was
      8%. Plasma HBP was significantly higher in severely injured patients and
      associated with shock on arrival, massive transfusions and organ failure. Septic
      patients had higher levels of HBP only on day 5. When evaluated for prediction of
      onset of sepsis during the two following days after plasma sampling by receiver
      operating characteristic (ROC) analyses, areas under the curves were non
      significant for all time points. Similar patterns were seen for CRP and WBC.
      CONCLUSION: In trauma patients, HBP levels are related to severity of injury and
      organ dysfunction. Heparin-binding protein was weakly associated with sepsis and
      only at the later stage of the observation period of 1 week. Moreover, HBP showed
      poor discriminatory properties as an early biomarker of post-injury sepsis.
      Trauma-induced inflammation during the post-injury phase may blunt the sepsis
      predictive performance of HBP.

PMID- 29569246
TI  - Expansion of airway basal epithelial cells from primary human non-small cell lung
      cancer tumors.
AB  - Pre-clinical non-small cell lung cancer (NSCLC) models are poorly representative
      of the considerable inter- and intra-tumor heterogeneity of the disease in
      patients. Primary cell-based in vitro models of NSCLC are therefore desirable for
      novel therapy development and personalized cancer medicine. Methods have been
      described to generate rapidly proliferating epithelial cell cultures from
      multiple human epithelia using 3T3-J2 feeder cell culture in the presence of Y
      27632, a RHO-associated protein kinase (ROCK) inhibitor, in what are known as
      "conditional reprograming conditions" (CRC) or 3T3 + Y. In some cancer studies,
      variations of this methodology have allowed primary tumor cell expansion across a
      number of cancer types but other studies have demonstrated the preferential
      expansion of normal epithelial cells from tumors in such conditions. Here, we
      report our experience regarding the derivation of primary NSCLC cell cultures
      from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution
      through Therapy (TRACERx) clinical study and discuss these in the context of
      improving the success rate for in vitro cultivation of cells from NSCLC tumors.

PMID- 29569248
TI  - Probing the molecular regulation of lipopolysaccharide stress in piglet liver by
      comparative proteomics analysis.
AB  - Lipopolysaccharide (LPS) can induce inflammatory responses in piglets, causing
      immunological stress and tissue damage. However, chronic LPS infection may lead
      to LPS-induced immunological stress resistance. The molecular mechanisms
      underlying LPS stress have not been fully elucidated. Here, we conducted a global
      comparative proteomics analysis to investigate the molecular regulation of LPS
      stress using an immunological stress model of weaned piglets. A shotgun-based
      SWATH-MS workflow was used for global proteomes of the piglet livers after 15-day
      LPS treatment. Out of 3700 quantified proteins, 93 proteins showed differential
      changes under LPS stress. Bioinformatics analysis indicated that the
      differentially expressed proteins were mainly involved in inflammatory response,
      oxidation-redox processes and defense reactions, and were enriched in a phagosome
      pathway. Several key proteins associated with oxidative stress (SOD2),
      inflammation response (STEAP4 and S100 family) and the phagosome pathway were
      verified by activity and targeted-MS analyses. The observed responses appear to
      mitigate hepatic damage due to excessive oxidative stress, inflammation, and
      repression of the phagosome pathway. Our results reveal that an increased STEAP4
      expression in piglets appears involved in cellular regulation by LPS stress and
      subsequent immunological stress resistance. This study sheds new light on the
      mechanism of prevention and relieving injury by LPS-induced immune responses.

PMID- 29569249
TI  - Effect of solvent on the extraction of phenolic compounds and antioxidant
      capacity of hazelnut kernel.
AB  - Hazelnut kernel phenolic compounds were recovered applying two different
      extraction approaches, namely ultrasound-assisted solid/liquid extraction (UA
      SLE) and solid-phase extraction (SPE). Different solvents were tested evaluating
      total phenolic compounds and total flavonoids contents together to antioxidant
      activity. The optimum extraction conditions, in terms of the highest value of
      total phenolic compounds extracted together to other parameters like simplicity
      and cost were selected for method validation and individual phenolic compounds
      analysis. The UA-SLE protocol performed using 0.1 g of defatted sample and 15 mL
      of extraction solvent (1 mL methanol/1 mL water/8 mL methanol 0.1% formic acid/5
      mL acetonitrile) was selected. The analysis of hazelnut kernel individual
      phenolic compounds was obtained by HPLC coupled with DAD and MS detections.
      Quantitative analysis was performed using a mixture of six phenolic compounds
      belonging to phenolic classes' representative of hazelnut. Then, the method was
      fully validated and the resulting RSD% values for retention time repeatability
      were below 1%. A good linearity was obtained giving R2 no lower than 0.997.The
      accuracy of the extraction method was also assessed. Finally, the method was
      applied to the analysis of phenolic compounds in three different hazelnut kernel
      varieties observing a similar qualitative profile with differences in the
      quantity of detected compounds.

PMID- 29569250
TI  - Impact of upper respiratory tract infections on perioperative outcomes of
      children undergoing therapeutic cardiac catheterisation.
AB  - BACKGROUND: Recent upper respiratory tract infection (URI) is associated with
      increased incidence of perioperative complications in children undergoing open
      heart surgery. As a result, surgery is often postponed. However, the effect of
      recent URI on the incidence of perioperative complications in children undergoing
      therapeutic cardiac catheterisation is unknown. We investigated the perioperative
      outcomes of congenital heart disease (CHD) children with recent URI who underwent
      elective therapeutic catheterisation. METHODS: We prospectively included children
      treated for CHD. Before surgery, parents or legal guardians were interviewed to
      complete a questionnaire on the child's demographics, history of asthma and
      passive smoking, and URI symptoms. Recorded perioperative respiratory adverse
      events (PRAEs) included laryngospasm, bronchospasm, breath holding, oxygen
      desaturation, and severe cough. Information on postoperative dysphoria, fever,
      copious sputum, and vomiting was obtained by telephone 24 h after surgery.
      RESULTS: Of 363 included children, 169 had recently (within 2 weeks) had a URI.
      The URI did not affect the incidence of laryngospasm, bronchospasm, breath
      holding, fever, or vomiting. The incidence of desaturation, severe cough,
      dysphoria, and copious sputum were significantly increased. Independent risk
      factors for PRAEs in children with a recent URI included age, passive smoking,
      and presence of rhinorrhoea or moist cough. The lengths of stay in the hospital
      and intensive care unit were not significantly different between groups.
      CONCLUSION: Although recent URI increased the incidence of PRAEs in children
      undergoing therapeutic cardiac catheterisation, most CHD patients with recent URI
      can undergo elective therapeutic cardiac catheterisation without serious adverse
      events or prolonged hospitalisation.

PMID- 29569251
TI  - Prenatal triptan exposure and neurodevelopmental outcomes in 5-year-old children:
      Follow-up from the Norwegian Mother and Child Cohort Study.
AB  - BACKGROUND: Triptans are commonly used to treat migraine headaches, but data on
      the long-term safety of these medications during pregnancy are sparse. Triptans
      have a biologically plausible mechanism for effects on the fetal brain through
      binding to 5-HT1 -receptors, and previous studies show increased risks of
      externalising behaviour problems in toddlers exposed to triptans during
      pregnancy. METHODS: We included 3784 children in the Norwegian Mother and Child
      Cohort Study, whose mothers returned the 5-year-questionnaire and reported a
      history of migraine or triptan use; 353 (9.3%) mothers reported use of triptans
      during pregnancy, 1509 (39.9%) reported migraine during pregnancy but no triptan
      use, and 1922 (50.8%) had migraine prior to pregnancy only. We used linear and
      log-binomial models with inverse probability weights to examine the association
      between prenatal triptan exposure and internalising and externalising behaviour,
      communication, and temperament in 5-year-old children. RESULTS: Triptan-exposed
      children scored higher on the sociability trait than unexposed children of
      mothers with migraine (beta 1.66, 95% confidence interval [0.30, 3.02]). We found
      no other differences in temperament, or increased risk of behaviour or
      communication problems. CONCLUSIONS: Contrary to results from previous studies in
      younger children, we found no increased risk of externalising behaviour problems
      in 5-year-old children exposed to triptans in fetal life. Triptan-exposed
      children did have slightly more sociable temperaments, but the clinical meaning
      of this finding is uncertain.

PMID- 29569252
TI  - The clinical features in Chinese patients with PRNP D178N mutation.
AB  - BACKGROUND AND PURPOSE: Fatal familial insomnia (FFI) is an autosomal dominant
      disease due to the D178N mutation of PRNP gene coupling with homozygous
      methionine (Met) at codon 129. It is generally considered that D178N mutation
      cases with 129 M/M homozygotes present as FFI, and 129 V/V as genetic CJD.
      However, the frequency of 129 Met alleles in Chinese population is much higher
      than that in Caucasians. This study aims to investigate the clinical features and
      genetic characteristics of Chinese D178N mutants in this genetic context.
      METHODS: We reviewed the clinical and genetic features of seven D178N patients.
      The clinical data, genetic data, electroencephalogram (EEG), brain magnetic
      resonance imaging (MRI), polysomnography (PSG), CSF 14-3-3 protein examinations
      of the seven patients were analyzed. RESULTS: The genotypes at codon 129 were all
      M/M. Four of the seven cases reported positive family history. Four patients were
      more likely the CJD phenotype and three were FFI phenotype according to the core
      clinical features. No major differences were found on the EEG, CSF 14-3-3
      protein, and PSG presentations between this study and western studies. Novel
      neuroimaging findings were two patients had typical neuroimaging abnormalities of
      CJD and frontotemporal dementia, respectively. CONCLUSIONS: Unlike the western
      populations, the diverse phenotypical presentations of D178N mutants were not
      simply determined by the 129 genotypes in Chinese. The underlying modifying
      factors for phenotypical variations warrant further investigations. For those
      with atypical clinical and imaging features, genetic testing was important for
      final diagnosis.

PMID- 29569253
TI  - Detection and management of atrial fibrillation after cryptogenic stroke or
      embolic stroke of undetermined source.
AB  - Cryptogenic stroke (CS) and embolic stroke of unknown source (ESUS) represent a
      major challenge to healthcare systems worldwide. Atrial fibrillation (AF) is
      commonly found after CS or ESUS. Independent of the mechanism of the index CS or
      ESUS, detection of AF in these patients offers the opportunity to reduce the risk
      of stroke recurrence by prescribing an anticoagulant instead of aspirin. The
      detection of AF may be pursued with different monitoring strategies. Comparison
      of monitoring strategies should take into account that AF detection rates
      reported in published studies, and then pooled in meta-analyses, are not only a
      function of the monitoring strategy itself, but also depend on patient-related,
      device-related, and study design-related factors. Once AF is found, the decision
      to anticoagulate a patient should be made on the basis of AF burden and the
      baseline risk of the patient. Empirical anticoagulation in patients with ESUS and
      no evidence of AF is an intriguing but still-unproven strategy and therefore
      should not be adopted outside of randomized clinical trials.

PMID- 29569255
TI  - Fetal Growth Restriction in Africa.

PMID- 29569254
TI  - Stem-cell therapy in ST-segment elevation myocardial infarction with reduced
      ejection fraction: A multicenter, double-blind randomized trial.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is a major determinant of
      long-term prognosis after ST-segment elevation myocardial infarction (STEMI).
      STEMI patients with reduced LVEF have a poor prognosis, despite successful
      reperfusion and the use of renin-angiotensin-aldosterone inhibitors. HYPOTHESIS:
      Intracoronary infusion of bone marrow-derived mononuclear cells (BMMC) may
      improve LVEF in STEMI patients successfully reperfused. METHODS: The main
      inclusion criteria for this double-blind, randomized, multicenter study were
      patient age 30 to 80 years, LVEF <=50%, successful angioplasty of infarct-related
      artery, and regional dysfunction in the infarct-related area analyzed before cell
      injection. Cardiac magnetic resonance imaging was used to assess LVEF, left
      ventricular volumes, and infarct size at 7 to 9 days and 6 months post-myocardial
      infarction. RESULTS: One hundred and twenty-one patients were included (66
      patients in the BMMC group and 55 patients in the placebo group). The primary
      endpoint, mean LVEF, was similar between both groups at baseline (44.63% +/-
      10.74% vs 42.23% +/- 10.33%; P = 0.21) and at 6 months (44.74% +/- 12.95 % vs
      43.50 +/- 12.43%; P = 0.59). The groups were also similar regarding the
      difference between baseline and 6 months (0.11% +/- 8.5% vs 1.27% +/- 8.93%; P =
      0.46). Other parameters of left ventricular remodeling, such as systolic and
      diastolic volumes, as well as infarct size, were also similar between groups.
      CONCLUSIONS: In this randomized, multicenter, double-blind trial, BMMC
      intracoronary infusion did not improve left ventricular remodeling or decrease
      infarct size.

PMID- 29569256
TI  - Job strain associated with increases in ambulatory blood and pulse pressure
      during and after work hours among female hotel room cleaners.
AB  - BACKGROUND: Previously documented elevated hypertension rates among Las Vegas
      hotel room cleaners are hypothesized to be associated with job strain. METHODS:
      Job strain was assessed by questionnaire. Ambulatory blood pressure (ABP) was
      recorded among 419 female cleaners from five hotels during 18 waking hours.
      Multiple linear regression models assessed associations of job strain with ABP
      and pulse pressure for 18-h, work hours, and after work hours. RESULTS: Higher
      job strain was associated with increased 18-h systolic ABP, after work hours
      systolic ABP, and ambulatory pulse pressure. Dependents at home but not social
      support at work attenuated effects. Among hypertensive workers, job strain
      effects were partially buffered by anti-hypertensive medication. CONCLUSIONS:
      High job strain is positively associated with blood pressure among female hotel
      workers suggesting potential for primary prevention at work. Work organizational
      changes, stress management, and active ABP surveillance and hypertension
      management should be considered for integrated intervention programs.

PMID- 29569257
TI  - Production of d-mannose from d-glucose by co-expression of d-glucose isomerase
      and d-lyxose isomerase in Escherichia coli.
AB  - BACKGROUND: d-Mannose is not only the epimer of d-glucose at the C-2 position,
      but also the aldose isomer of d-fructose. Because of its physiological properties
      and health benefits, d-mannose has attracted public interest. It has been
      confirmed that d-mannose has broad applications in food, cosmetics, and
      pharmaceutical industries. According to the Izumoring strategy, d-glucose
      isomerase (d-GI) and d-lyxose isomerase (d-LI) play important roles in the
      conversions of d-fructose from d-glucose and of d-mannose from d-fructose
      respectively. In this study, a one-step enzyme process of d-mannose production
      from d-glucose has been constructed by co-expression of the d-GI from
      Acidothermus cellulolyticus and d-LI from Thermosediminibacter oceani in
      Escherichia coli BL21(DE3) cells. RESULTS: The co-expression system exhibits
      maximum activity at pH 6.5 and 65  degrees C with Co2+ supplement. It is
      relatively thermostable at less than 65  degrees C. When the reaction reaches
      equilibrium, the ratio of d-glucose, d-fructose, and d-mannose is approximately
      34 : 49.6 : 16.4. By using this co-expression system, about 60.0 g L-1 d-mannose
      is obtained from 400 g L-1 d-glucose in 8 h. CONCLUSION: This co-expression of d
      GI and d-LI system provides a novel and efficient approach for d-mannose
      production. (c) 2018 Society of Chemical Industry.

PMID- 29569258
TI  - Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus
      on Merkel cells.
AB  - Cutaneous ganglioneuromas (CGNs) are exceptional. We aim to describe the
      anatomico-clinical profile of primary CGN and report 4 cases. Patients were 2 men
      and 2 women aged 53 to 76 years, who had flesh-colored nodules on the back,
      associated with adjacent keratotic changes, that is, epidermal nevus (1 case) or
      seborrheic keratosis (3 cases). Histopathology showed ganglion cells within a
      proliferation of Schwann cells. The epidermis was acanthotic, associated with
      sebaceous induction in 2 cases, with follicular hyperplasia as in fibroepithelial
      tumors (1 case) or with tricholemmoma (2 cases). Cytokeratin-20 immunostaining
      showed Merkel cells in the epidermis. A higher density of Merkel cells was
      observed in BerEP4+ follicular structures. Along with 16 published cases, our
      study indicates that a nodule associated with seborrheic keratosis on the back
      may represent a CGN, a complex mesenchymal and epidermal/follicular lesion of
      neuroectodermal lineage, associating neuronal proliferation and Merkel cell
      hyperplasia with follicular induction.

PMID- 29569259
TI  - Varicocele is the root cause of BPH: Destruction of the valves in the spermatic
      veins produces elevated pressure which diverts undiluted testosterone directly
      from the testes to the prostate.
AB  - In varicocele, there is venous flow of free testosterone (FT) directly from the
      testes into the prostate. Intraprostatic FT accelerates prostate cell production
      and prolongs cell lifespan, leading to the development of BPH. We show that in a
      large group of patients presenting with BPH, bilateral varicocele is found in all
      patients. A total of 901 patients being treated for BPH were evaluated for
      varicocele. Three diagnostic methods were used as follows: physical examination,
      colour flow Doppler ultrasound and contact liquid crystal thermography. Bilateral
      varicocele was found in all 901 patients by at least one of three diagnostic
      methods. Of those subsequently treated by sclerotherapy, prostate volume was
      reduced in more than 80%, with prostate symptoms improved. A straightforward
      pathophysiologic connection exists between bilateral varicocele and BPH. The
      failure of the one-way valves in the internal spermatic veins leads to a cascade
      of phenomena that are unique to humans, a result of upright posture. The prostate
      is subjected to an anomalous venous supply of undiluted, bioactive free
      testosterone. FT, the obligate control hormone of prostate cells, reaches the
      prostate directly via the venous drainage system in high concentrations,
      accelerating the rate of cell production and lengthening cell lifespan, resulting
      in BPH.

PMID- 29569260
TI  - Down-regulation of microRNA-375 regulates adipokines and inhibits inflammatory
      cytokines by targeting AdipoR2 in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has been considered as a multi
      factorial metabolic syndrome. MicroRNA-375 (MiR-375) was significantly up
      regulated in serum of NAFLD patients and the role of miR-375 was addressed as a
      putative biomarker of NAFLD progression. However, the specific function of miR
      375 in the progression of NAFLD is still unclear and the molecular mechanisms
      underlying NAFLD have yet to be elucidated. Our study aimed at investigating the
      regulatory role of miR-375 in the molecular mechanisms of the pathogenic
      progression of NAFLD and to find out whether miR-375 regulates the expression
      level of adipokines and inflammatory cytokines in NAFLD. We found that miR-375
      expression was increased in the serum of high fat diet (HFD)-feeding mice
      comparing to that in healthy controls, whereas the expression of Adiponectin
      receptor 2 (AdipoR2) was decreased in mice fed with HFD. Moreover, inhibiton of
      miR-375 up-regulated the expression of Adiponectin, inhibited the lipid
      accumulation and down-regulated both the level of Leptin and inflammatory
      cytokines including tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in
      palmiticacid (PA)-induced human hepatocellular carcinoma HepG2 cells. In
      addition, we also found that AdipoR2 was a target of miR-375 by binding directly
      to the 3'UTR of it. Of note, the reduced level of TNF-alpha, IL-6 as well as
      Leptin and the production of Adiponectin by miR-375 inhibitors was significantly
      reversed by silencing of AdipoR2 in PA-induced HepG2 cells. Our findings bring
      new insight into understanding the complex mechanisms underlying the pathogenesis
      of NAFLD and provide evidence that miR-375 might represent a novel therapeutic
      target for NAFLD.

PMID- 29569261
TI  - Activity-guided isolation of phase II enzyme inducers from buckwheat flour
      methanolic extracts.
AB  - BACKGROUND: Buckwheat is an important alternative crop and a raw material for
      functional food formulation. Phase II detoxification proteins/enzymes provide
      cytoprotective roles against oxidative stress and inflammation originating from
      various stressors. We aimed to identify and characterize potential phase II
      enzyme inducers from methanolic extracts of buckwheat flour, using an activity
      guided fractionation based on the induction of quinone reductase (QR) (EC
      1.6.5.2) in Hepa 1c1c7 cells. RESULTS: We isolated the QR inducers N-trans
      feruloyltyramine (I), syringic acid (II), quercetin (III) and myricetin (IV). The
      relative QR-inducing ability, as well as the concentration required to double QR
      specific activity (CD values, in parentheses), decreased in the order: quercetin
      (3.0 umol L-1 ) > N-trans-feruloyltyramine (24 umol L-1 ) > myricetin (58 umol L
      1 ) > syringic acid (5.4 mmol L-1 ). Quercetin and N-trans-feruloyltyramine
      exhibited the greatest extent of QR induction of an approximately four-fold
      maximum induction and these compounds also exhibited the greatest values for the
      ratio of IC50 (i.e. level to reduce viability by 50%): CD values of 11 and > 8.3,
      respectively, among the four QR inducers isolated. Isobologram analyses for
      binary combinations of compounds I-IV revealed primarily antagonistic
      interactions for QR induction. CONCLUSION: These findings add to our
      understanding of the nutraceutical potential of buckwheat as a chemoprophylactic
      dietary component. (c) 2018 Society of Chemical Industry.

PMID- 29569262
TI  - Application of the RAND-UCLA Appropriateness Methodology to a Large
      Multidisciplinary Stakeholder Group Evaluating the Validity and Feasibility of
      Patient-Centered Standards in Geriatric Surgery.
AB  - OBJECTIVES: To explore (1) differences in validity and feasibility ratings for
      geriatric surgical standards across a diverse stakeholder group (surgeons vs.
      nonsurgeons, health care providers vs. nonproviders, including patient-family,
      advocacy, and regulatory agencies); (2) whether three multidisciplinary
      discussion subgroups would reach similar conclusions. DATA SOURCE/STUDY SETTING:
      Primary data (ratings) were reported from 58 stakeholder organizations. STUDY
      DESIGN: An adaptation of the RAND-UCLA Appropriateness Methodology (RAM) process
      was conducted in May 2016. DATA COLLECTION/EXTRACTION METHODS: Stakeholders self
      administered ratings on paper, returned via mail (Round 1) and in-person (Round
      2). PRINCIPAL FINDINGS: In Round 1, surgeons rated standards more critically
      (91.2 percent valid; 64.9 percent feasible) than nonsurgeons (100 percent valid;
      87.0 percent feasible) but increased ratings in Round 2 (98.7 percent valid; 90.6
      percent feasible), aligning with nonsurgeons (99.7 percent valid; 96.1 percent
      feasible). Three parallel subgroups rated validity at 96.8 percent (group 1), 100
      percent (group 2), and 97.4 percent (group 3). Feasibility ratings were 76.9
      percent (group 1), 96.1 percent (group 2), and 92.2 percent (group 3).
      CONCLUSIONS: There are differences in validity and feasibility ratings by health
      professions, with surgeons rating standards more critically than nonsurgeons.
      However, three separate discussion subgroups rated a high proportion (96-100
      percent) of standards as valid, indicating the RAM can be successfully applied to
      a large stakeholder group.

PMID- 29569263
TI  - Brush Day & Night Phase III to Phase IV: ensuring that good oral health habits
      are sustainable.
AB  - Over the past 10 years, the FDI-Unilever Brush Day & Night partnership has
      significantly influenced the life of children worldwide through the
      implementation of school programmes for oral health education and prevention.
      This article reports the key facts and outcomes of Phase III of the partnership,
      and announces the launch of Phase IV. During Phase III, the expert advisors of
      the Brush Day & Night partnership conducted a longitudinal study to evaluate the
      impact of the '21 Day' programme in almost 8,000 children in 10 countries.
      Analysis revealed the effectiveness of the 21 Day programme in sustainably
      educating children to brush their teeth twice a day, with the greatest impact
      observed in children aged 7-9 years. With the launch of Phase IV, the Brush Day &
      Night partnership will continue to deliver its oral health school programme for 7
      9 year-old children with a strengthened methodology, including randomized
      sampling and control groups. The scope of the evaluation will be broadened to
      include oral health-related quality of life indicators, and monitoring of the
      oral health knowledge of children's parents/carers.

PMID- 29569264
TI  - Cloning, expression profiling, and acetylation identification of alpha-tubulin N
      acetyltransferase 1 from Bombyx mori.
AB  - Alpha-tubulin N-acetyltransferase 1 (ATAT1) is an acetyltransferase specific to
      alpha-tubulin and performs important functions in many cellular processes. Bombyx
      mori is an economic insect and also known as a model lepidoptera insect. In this
      study, we cloned a B. mori ATAT1 gene (BmATAT1) (Gen Bank accession number:
      XP_004932777.1). BmATAT1 contained an open reading frame (ORF) of 1,065 bp
      encoding 355 amino acids (aa). Expression profiling of BmATAT1 protein showed
      that the expression levels of BmATAT1 at different developmental stages and
      different tissues in fifth-instar larvae differ. BmATAT1 was highly expressed at
      the egg stage and in the head of the fifth-instar larvae. Subcellular
      localization showed that BmATAT1 was distributed in the cytoplasm and nucleus.
      Furthermore, BmATAT1 may lead to time-dependent induction of cell cycle arrest in
      the G2/M phase by flow cytometry analysis. Interestingly, using site-specific
      mutation, immunoprecipitation, and Western blotting, we further found a BmATAT1
      acetylated site at K156, suggesting that this acetyltransferase could be
      regulated by acetylation itself.

PMID- 29569265
TI  - Three-dimensional speckle tracking echocardiography-derived left atrial
      deformation analysis in acromegaly (Results from the MAGYAR-Path Study).
AB  - INTRODUCTION: Acromegaly is a chronic and disfiguring hormonal disease caused by
      a benign growth hormone-secreting pituitary adenoma in most of the cases. The
      objective of this study was to investigate three-dimensional (3D) speckle
      tracking echocardiography (3DSTE)-derived left atrial (LA) volumetric and
      functional properties in patients with acromegaly. It was also examined whether
      the activity of acromegaly is associated with further alterations in these LA
      parameters. METHODS: A total of 23 patients with acromegaly were involved in this
      study. Due to inadequate image quality, 4 patients were excluded from the 3DSTE
      analysis. The mean age of the remaining acromegalic subjects was 58.5 +/- 13.1
      years (7 males). The control group consisted of 21 age- and gender-matched
      healthy subjects (mean age 51.8 +/- 10.3 years, 10 males). RESULTS: Maximum (44.8
      +/- 12.7 mL vs 78.7 +/- 25.4 mL, P < .05), minimum (24.1 +/- 9.0 mL vs 44.5 +/-
      15.5 mL, P < .05), and preatrial contraction (35.5 +/- 11.2 mL vs 66.0 +/- 22.8
      mL, P < .05) LA volumes were significantly different between all acromegaly
      patients compared with controls. Increased peak global and mean segmental radial
      and 3D strains and decreased LA circumferential strain (CS) could be detected in
      all acromegaly patients as compared to healthy subjects. Significant correlation
      could be detected between insulin-like growth factor 1 (IGF-1) index and peak
      superior LA-CS (r = .49, P = .05) in acromegaly. CONCLUSION: Acromegaly is
      associated with increased LA volumes and changes in LA functional properties.

PMID- 29569267
TI  - Defining the optimal sensory environment in the NICU: an elusive task.

PMID- 29569266
TI  - A late presentation of congenital cardiac anomaly: Accessory chordae from the
      left atrium causing severe mitral regurgitation.
AB  - Mitral regurgitation secondary to accessory mitral valve (MV) chordae of the left
      atrium is an extremely rare congenital disease. A 85-year-old female (NYHA I-II)
      was hospitalized for investigations. An echocardiogram showed calcification of
      the MV with mild stenosis and moderate regurgitation. Transesophageal three
      dimensional echocardiogram revealed a band-like structure extending from the
      distal third of the anterior wall of the left atrium to the MV. This accessory
      chordae determined severe systolic regurgitation and mild mitral stenosis. The
      patient was referred for consideration of cardiac surgery but was refused for
      comorbidities and anatomy. Usually aberrant chordae determinant valvulopathies
      are detected and treated at a much younger age. The delay of the symptoms could
      be explained in our case with the progressive growth and dilatation of the left
      atrium causing traction of the aberrant chord resulting in an increase in the
      leaflet prolapse and regurgitation.

PMID- 29569268
TI  - Case of mild X-linked ichthyosis complicated with paroxysmal supraventricular
      tachycardia and anemia.

PMID- 29569269
TI  - Detection of Borrelia in Ixodes scapularis ticks by silver stain,
      immunohistochemical and direct immunofluorescent methods.
AB  - BACKGROUND: Lyme disease (LD) is one of the most common tick-borne diseases
      caused by several Borrelia species of spirochetes. Ixodes scapularis is
      responsible for the transmission of LD in the northeastern United States. The
      rate of infection varies with the duration of tick attachment to the host;
      however, this information may be unknown. In skin biopsies, it is often difficult
      to identify spirochetes. Testing of ticks is not routinely performed. Treatment
      is established by clinical presentation. OBJECTIVE: To test paraffin-embedded I.
      scapularis ticks for Borrelia by different methods. MATERIALS/METHODS: We
      examined 20 paraffin-embedded ticks by silver stain, immunohistochemical (IHC)
      and direct immunofluorescent (DIF) methods and compared the percentage of
      positivity with DIF results from the Connecticut Agricultural Experiment Station.
      RESULTS: The results were similar by DIF, which proved to be the most sensitive
      method, followed by the silver stain and IHC. CONCLUSION: We found that the
      identification of spirochetes in paraffin-embedded ticks was less difficult than
      in tissue with a comparable turnaround time to that of a routine biopsy. Timely
      identification of Borrelia in ticks may influence the clinical management of the
      patients.

PMID- 29569270
TI  - Effect of nutritional status on arsenic and smokeless tobacco induced
      genotoxicity, sperm abnormality and oxidative stress in mice in vivo.
AB  - BACKGROUND: Recently, high concentrations of arsenic have been documented in
      ground waters of Southern Assam, India. Indiscriminate smokeless tobacco
      consumption is a common practice in this region. Correlation between nutritional
      status and arsenic and smokeless tobacco-induced health effects has not been
      taken up in humans or other test systems. METHODS: Mice were divided into groups
      based on protein (casein) content in the diet: High protein (40%), optimum
      protein (20%), and low protein (5%). Simultaneous chronic exposure (90 days) to
      arsenic and smokeless tobacco (sadagura) orally was given to evaluate the extent
      of the cytological and genotoxicological damage. Micronucleus assay and Comet
      assay of the femur bone marrow cells were conducted. Germ cell toxicity was
      evaluated by recording the sperm head abnormalities and total sperm count. Cell
      cycle analysis was performed in femur bone marrow cells using flow cytometer.
      Hepatic, renal, and intestinal tissues were analyzed for various oxidative stress
      evaluations. Histological examination of liver and kidney was performed. RESULTS:
      Notably, high protein diet groups had lower arsenic and sadagura induced
      genotoxicity, germ cell abnormalities and oxidative stress as compared to optimum
      protein and low protein diet counterparts. CONCLUSION: Our study indicates that
      sufficient levels of dietary protein appear to reduce the long-term arsenic and
      smokeless tobacco-induced toxicity in mice test system, as compared to lower or
      deficient amount of protein in the diet. This observation has implications and
      invites further studies especially epidemiological studies in the human
      population exposed to arsenic in South East Asian countries. Environ. Mol.
      Mutagen. 59:386-400, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29569271
TI  - Trichoscopy of alopecia areata: An update.
AB  - The diagnosis of alopecia areata is usually based on clinical manifestations.
      However, there are several hair and scalp disorders that share similar clinical
      features with alopecia areata, such as tinea capitis, trichotillomania or
      traction alopecia. Trichoscopy as a fast, non-invasive and easy-to-perform
      technique may help to identify subtle details and establish the correct
      diagnosis. The aim of this review is to present the spectrum of trichoscopic
      findings in alopecia areata. A systematic review of the published work was
      performed by searching the PubMed, Scopus and EBSCO databases, complemented by a
      thorough hand search of reference lists. Of 427 articles retrieved, 30 studies
      were eligible for quantitative analysis. The reported features of alopecia areata
      were: yellow dots (6-100% patients), short vellus hairs (34-100%), black dots (0
      84%), broken hairs (0-71%) and exclamation mark hairs (12-71%). Tapered hairs (5
      81%) were reported in few studies, but a relatively high frequency of this
      finding in alopecia areata may indicate their important role in the differential
      diagnosis of hair loss. Rarely reported features, which include upright regrowing
      hairs (11-96%), pigtail (circle) hairs (4-61%) and Pohl-Pinkus constrictions (2
      10%), may also be helpful in the diagnosis of alopecia areata. There is no
      pathognomonic trichoscopic marker for alopecia areata and the most common
      trichoscopic features are not the most specific. Therefore, the diagnosis should
      be based on the coexistence of several trichoscopic findings, not on the presence
      of a single feature.

PMID- 29569272
TI  - Anti/genotoxic, longevity inductive, cytotoxic, and clastogenic-related
      bioactivities of tomato and lycopene.
AB  - The aim of this study was to evaluate some biological activities of tomato as
      well as lycopene and to consider a new nutraceutic value for this fruit regarding
      to the protection against genetic damage and as a chemopreventive agent.
      Genotoxicity, DNA-protection against hydrogen peroxide, and lifespan properties
      of tomato and lycopene were assessed through wing spot test and longevity assay
      using the Drosophila in vivo model. Additionally, chemopreventive activity was
      investigated through cytotoxicity, DNA-fragmentation comet and annexin V FITC/PI
      assays using HL60 in vitro model. Results showed that: (i) tomato and lycopene
      are not genotoxic and protect against H2 O2 -induced damage; (ii) with respect to
      the lifespan, tomato and lycopene are harmless at the lowest concentration; (iii)
      tomato is cytotoxic in a dose-dependent manner, but not lycopene; (iv) tomato and
      lycopene do not induce internucleosomal DNA-fragmentation although they induce
      significant clastogenic activity at low level in the leukemia cells. To sum up,
      tomato is a good candidate to be considered as a nutraceutical substance.
      Furthermore, synergistic action among other components within tomato matrix could
      be the cause of the health effects observed in this vegetable, which are not
      fully explained by lycopene. Environ. Mol. Mutagen. 59:427-437, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29569273
TI  - The predictive value of global longitudinal strain on clinical outcome in
      patients with ST-segment elevation myocardial infarction and preserved systolic
      function.
AB  - BACKGROUND: Left ventricular ejection fraction (LVEF) is fundamental for risk
      stratification after ST-segment elevation myocardial infarction (STEMI). However,
      it lacks discrimination power within normal range. Novel echocardiographic
      deformation parameters may be of benefit for those with post-MI preserved LVEF.
      OBJECTIVES: We hypothesized that semiautomated calculation of baseline global
      longitudinal strain (GLS) can identify high-risk group among patients with LVEF
      >= 50% following STEMI. METHODS: During the period from January to July 2017, 110
      patients with successful reperfusion of STEMI and LVEF >= 50% were prospectively
      included. Within 48 hours, patients underwent a baseline GLS study with follow-up
      study at 30 days. The endpoint was a composite of cardiovascular mortality,
      rehospitalization for heart failure, and urgent revascularization. RESULTS: Mean
      GLS value changed from -16 +/- 4% at baseline to -12 +/- 4% at 30-day follow-up
      (P < .001). At 30 days, cardiovascular mortality was reported in 4.5%, 11.8% were
      rehospitalized due to heart failure, and 5.4% underwent urgent revascularization.
      ROC curve analysis showed that a cutoff baseline GLS value >-12.65% predicted 30
      day MACEs with a sensitivity and specificity of 77.8% and 83.7%, respectively
      (AUC 0.784, 95% CI 0.646-0.921, P < .001). An adjusted multivariate logistic
      regression analysis revealed that baseline GLS value >-12.65% to be the only
      significant independent predictor for occurrence of MACEs (OR 19.54, 95% CI 6.3
      61.1, P < .001). CONCLUSION: Early GLS calculation predicts 30-day outcome in
      patients with preserved LVEF following reperfusion of STEMI.

PMID- 29569275
TI  - Emotional intelligence and attentional bias for threat-related emotion under
      stress.
AB  - Emotional intelligence (EI) can buffer potentially harmful effects of situational
      and chronic stressors to safeguard psychological wellbeing (e.g., Mikolajczak,
      Petrides, Coumans & Luminet, ), yet understanding how and when EI operates to
      promote adaptation remains a research priority. We explored whether EI (both
      trait and ability) modulated early attentional processing of threat-related
      emotion under conditions of stress. Using a dot probe paradigm, eye movement
      (fixation to emotive facial stimuli, relative to neutral) and manual reaction
      time data were collected from 161 adults aged 18-57 years (mean age = 25.24; SD =
      8.81) exposed to either a stressful (failure task) or non-stressful (control)
      situation. Whilst emotion management ability and trait wellbeing corresponded to
      avoidance of negative emotion (angry and sad respectively), high trait
      sociability and emotionality related to a bias for negative emotions. With most
      effects not restricted to stressful conditions, it is unclear whether EI
      underscores 'adaptive' processing, which carries implications for school-based
      social and emotional learning programs.

PMID- 29569274
TI  - The effects of acetaldehyde exposure on histone modifications and chromatin
      structure in human lung bronchial epithelial cells.
AB  - As the primary metabolite of alcohol and the most abundant carcinogen in tobacco
      smoke, acetaldehyde is linked to a number of human diseases associated with
      chronic alcohol consumption and smoking including cancers. In addition to direct
      DNA damage as a result of the formation of acetaldehyde-DNA adducts, acetaldehyde
      may also indirectly impact proper genome function through the formation of
      protein adducts. Histone proteins are the major component of the chromatin. Post
      translational histone modifications (PTMs) are critically important for the
      maintenance of genetic and epigenetic stability. However, little is known about
      how acetaldehyde-histone adducts affect histone modifications and chromatin
      structure. The results of protein carbonyl assays suggest that acetaldehyde forms
      adducts with histone proteins in human bronchial epithelial BEAS-2B cells. The
      level of acetylation for N-terminal tails of cytosolic histones H3 and H4, an
      important modification for histone nuclear import and chromatin assembly, is
      significantly downregulated following acetaldehyde exposure in BEAS-2B cells,
      possibly due to the formation of histone adducts and/or the decrease in the
      expression of histone acetyltransferases. Notably, the level of nucleosomal
      histones in the chromatin fraction and at most of the genomic loci we tested are
      low in acetaldehyde-treated cells as compared with the control cells, which is
      suggestive of inhibition of chromatin assembly. Moreover, acetaldehyde exposure
      perturbs chromatin structure as evidenced by the increase in general chromatin
      accessibility and the decrease in nucleosome occupancy at genomic loci following
      acetaldehyde treatment. Our results indicate that regulation of histone
      modifications and chromatin accessibility may play important roles in
      acetaldehyde-induced pathogenesis. Environ. Mol. Mutagen. 59:375-385, 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 29569276
TI  - Is desiccation tolerance and avoidance reflected in xylem and phloem anatomy of
      two coexisting arid-zone coniferous trees?
AB  - Plants close their stomata during drought to avoid excessive water loss, but
      species differ in respect to the drought severity at which stomata close. The
      stomatal closure point is related to xylem anatomy and vulnerability to embolism,
      but it also has implications for phloem transport and possibly phloem anatomy to
      allow sugar transport at low water potentials. Desiccation-tolerant plants that
      close their stomata at severe drought should have smaller xylem conduits and/or
      fewer and smaller interconduit pits to reduce vulnerability to embolism but more
      phloem tissue and larger phloem conduits compared with plants that avoid
      desiccation. These anatomical differences could be expected to increase in
      response to long-term reduction in precipitation. To test these hypotheses, we
      used tridimensional synchroton X-ray microtomograph and light microscope imaging
      of combined xylem and phloem tissues of 2 coniferous species: one-seed juniper
      (Juniperus monosperma) and pinon pine (Pinus edulis) subjected to precipitation
      manipulation treatments. These species show different xylem vulnerability to
      embolism, contrasting desiccation tolerance, and stomatal closure points. Our
      results support the hypothesis that desiccation tolerant plants require higher
      phloem transport capacity than desiccation avoiding plants, but this can be
      gained through various anatomical adaptations in addition to changing conduit or
      tissue size.

PMID- 29569277
TI  - Use of genetic, climatic, and microbiological data to inform reintroduction of a
      regionally extinct butterfly.
AB  - Species reintroductions are increasingly used as means of mitigating biodiversity
      loss. Besides habitat quality at the site targeted for reintroduction, the choice
      of source population can be critical for success. The butterfly Melanargia
      russiae (Esper's marbled white) was extirpated from Hungary over 100 years ago,
      and a reintroduction program has recently been approved. We used museum specimens
      of this butterfly, mitochondrial DNA data (mtDNA), endosymbiont screening, and
      climatic-similarity analyses to determine which extant populations should be used
      for its reintroduction. The species displayed 2 main mtDNA lineages across its
      range: 1 restricted to Iberia and southern France (Iberian lineage) and another
      found throughout the rest of its range (Eurasian lineage). These 2 lineages
      possessed highly divergent wsp alleles of the bacterial endosymbiont Wolbachia.
      The century-old Hungarian specimens represented an endemic haplotype belonging to
      the Eurasian lineage, differing by one mutation from the Balkan and eastern
      European populations. The Hungarian populations of M. russiae occurred in areas
      with a colder and drier climate relative to most sites with extant known
      populations. Our results suggest the populations used for reintroduction to
      Hungary should belong to the Eurasian lineage, preferably from eastern Ukraine
      (genetically close and living in areas with the highest climatic similarity).
      Materials stored in museum collections can provide unique opportunities to
      document historical genetic diversity and help direct conservation.

PMID- 29569278
TI  - Lenalidomide treatment of myelodysplastic syndromes with chromosome 5q deletion:
      Results from the National Registry of the Italian Drug Agency.
AB  - OBJECTIVE: The most typical cytogenetic aberration in myelodysplastic syndromes
      is del(5q), which, when isolated, is associated with refractory anaemia and good
      prognosis. Based on high rates of erythroid response and transfusion
      independence, Lenalidomide (LEN) became the standard treatment. This multi-centre
      study was designed to supplement Italian Registry data on LEN by addressing
      prescription, administration appropriateness, haematological and cytogenetic
      responses and disease evolution. METHODS: MORE study was an observational, non
      interventional, multi-centre, retrospective and prospective study. Cases were
      recruited from 45 Haematological Centres throughout Italy. Data were collected
      from the Italian National Registry for Lenalidomide administration and
      supplemented by a MORE data form. RESULTS: Data from 190/213 patients were
      analysed. In all, 149 had been diagnosed by conventional cytogenetics (GROUP A)
      and 41 only by FISH (GROUP B). Overall erythroid response was obtained in 92.8%
      of cases. Overall cytogenetic remission was achieved in 22.6% of cases. Disease
      progression occurred in 15.6% of cases. Clonal cytogenetic evolution
      characterised progression to AML but not to higher risk MDS. CONCLUSIONS:
      Erythroid response to Lenalidomide was similar in MDS with isolated del(5q) and
      with del(5q) plus one anomaly. Progression to AML or higher risk MDS showed
      different cytogenetic features.

PMID- 29569279
TI  - Role of prephase treatment prior to definitive chemotherapy in patients with
      diffuse large B-cell lymphoma.
AB  - BACKGROUND: During the treatment of diffuse large B-cell lymphoma (DLBCL)
      patients, treatment-related toxicities are higher in the initial phase of
      treatment (First cycle effect). Toxicities can be tumor lysis syndrome,
      deterioration in performance status, febrile neutropenia, and rarely mortality.
      Prephase treatment before definitive chemotherapy is used in European countries
      to alleviate these toxicities. METHODS: This was a non-randomized study carried
      out with the aim to evaluate the role of prephase treatment given prior to
      definitive chemotherapy in newly diagnosed DLBCL patients. Patients were divided
      into 2 cohorts "prephase cohort" and "non-prephase cohort." Prephase cohort
      received prephase treatment consisting of vincristine (1 mg) on -6th day and
      prednisolone 100 mg daily for 7 days (-6th day to day 0). Prephase treatment was
      followed by CHOP/R-CHOP chemotherapy on day 1. Non-prephase cohort received
      chemotherapy without prephase. Both groups were followed up for 30 days post
      first cycle chemotherapy. RESULTS: A total of 100 patients with DLBCL (50 in each
      cohort) were enrolled. There was a significant improvement in performance status
      of the patients who received prephase. A majority of 92% patients attained ECOG
      performance status of either 0 or 1 before starting chemotherapy in the prephase
      cohort. Febrile neutropenia was lower (16%) in the prephase cohort as compared
      with the non-prephase cohort (34%; P = .037). CONCLUSION: Prephase treatment
      prior to definitive chemotherapy (CHOP +/- Rituximab) improves the performance
      status and decreases first cycle effect in DLBCL patients.

PMID- 29569280
TI  - Developing High-Performance Lithium Metal Anode in Liquid Electrolytes:
      Challenges and Progress.
AB  - Lithium metal anodes are potentially key for next-generation energy-dense
      batteries because of the extremely high capacity and the ultralow redox
      potential. However, notorious safety concerns of Li metal in liquid electrolytes
      have significantly retarded its commercialization: on one hand, lithium metal
      morphological instabilities (LMI) can cause cell shorting and even explosion; on
      the other hand, breaking of the grown Li arms induces the so-called "dead Li";
      furthermore, the continuous consumption of the liquid electrolyte and cycleable
      lithium also shortens cell life. The research community has been seeking new
      strategies to protect Li metal anodes and significant progress has been made in
      the last decade. Here, an overview of the fundamental understandings of solid
      electrolyte interphase (SEI) formation, conceptual models, and advanced real-time
      characterizations of LMI are presented. Instructed by the conceptual models,
      strategies including increasing the donatable fluorine concentration (DFC) in
      liquid to enrich LiF component in SEI, increasing salt concentration (ionic
      strength) and sacrificial electrolyte additives, building artificial SEI to boost
      self-healing of natural SEI, and 3D electrode frameworks to reduce current
      density and delay Sand's extinction are summarized. Practical challenges in
      competing with graphite and silicon anodes are outlined.

PMID- 29569281
TI  - Ruptured mitral valve aneurysm: A devastating complication of aortic valve
      endocarditis.
AB  - Mitral valve aneurysm is a rare clinical entity that is mostly resulted from
      infective endocarditis, in particular, aortic valve endocarditis. Once mitral
      valve aneurysm ruptures and severe mitral regurgitation and hemodynamic
      instability develop, prompt surgery should be considered. Here we report a
      patient with ruptured mitral valve aneurysm associated with native aortic valve
      endocarditis that was improved after a successful mitral and aortic valve
      replacement surgery associated with antibiotic therapy for 6 weeks.

PMID- 29569282
TI  - Fractional flow reserve-CT assessment of coronary stenosis.
AB  - Coronary computed tomography angiography (CCTA) has been an established
      noninvasive method for detection of coronary artery disease (CAD). Although CCTA
      has had a high sensitivity and negative predictive value for CAD detection,
      specificity for obstructive CAD has been relatively low, partly due to coronary
      calcium, imaging artifacts, and other factors leading to an overestimation of
      stenosis severity. A relatively new noninvasive method of calculation of
      fractional flow reserve (FFR) using CCTA (FFRCT ) data has been developed. This
      noninvasive method yields similar results to invasive FFR measurement, improving
      specificity for noninvasively detecting lesion-specific ischemia thus helping
      guide revascularization.

PMID- 29569283
TI  - An Earth-Abundant Catalyst-Based Seawater Photoelectrolysis System with 17.9%
      Solar-to-Hydrogen Efficiency.
AB  - The implementation of water splitting systems, powered by sustainable energy
      resources, appears to be an attractive strategy for producing high-purity H2 in
      the absence of the release of carbon dioxide (CO2 ). However, the high cost,
      impractical operating conditions, and unsatisfactory efficiency and stability of
      conventional methods restrain their large-scale development. Seawater covers 70%
      of the Earth's surface and is one of the most abundant natural resources on the
      planet. New research is looking into the possibility of using seawater to produce
      hydrogen through electrolysis and will provide remarkable insight into
      sustainable H2 production, if successful. Here, guided by density functional
      theory (DFT) calculations to predict the selectivity of gas-evolving catalysts, a
      seawater-splitting device equipped with affordable state-of-the-art
      electrocatalysts composed of earth-abundant elements (Fe, Co, Ni, and Mo) is
      demonstrated. This device shows excellent durability and specific selectivity
      toward the oxygen evolution reaction in seawater with near 100% Faradaic
      efficiency for the production of H2 and O2 . Powered by a single commercial III-V
      triple-junction photovoltaic cell, the integrated system achieves spontaneous and
      efficient generation of high-purity H2 and O2 from seawater at neutral pH with a
      remarkable 17.9% solar-to-hydrogen efficiency.

PMID- 29569284
TI  - Low frequency of acetyl salicylic acid hypersensitivity in mastocytosis: The
      results of a double-blind, placebo-controlled challenge study.
AB  - BACKGROUND: Patients with mastocytosis are at increased risk of anaphylaxis. The
      use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often discouraged because
      of this reason. However, the actual prevalence and severity of NSAID-related
      hypersensitivity among patients with mastocytosis is unknown. METHODS: A double
      blind, placebo-controlled acetylsalicylic acid (ASA) challenge up to a cumulative
      dose of 520 mg was performed among adult patients with mastocytosis. In addition,
      a retrospective search of the entire outpatient cohort was performed to obtain
      "real-life" data on NSAID hypersensitivity. RESULTS: Fifty patients underwent an
      ASA challenge. Seventy percent had indolent systemic mastocytosis, 18% had
      mastocytosis in the skin, and 12% had advanced mastocytosis. The ASA challenge
      was positive in 1 patient who developed urticaria. The additional retrospective
      chart review revealed that 8 of 191 patients had a history of NSAID-related
      hypersensitivity reaction(s), of whom 3 reported severe systemic reactions. All 8
      patients had already experienced NSAID-related hypersensitivity reactions before
      mastocytosis was diagnosed. CONCLUSIONS: The frequency of ASA hypersensitivity
      was 2% in a prospective challenge study and 4.1% in a retrospective chart review
      of 191 patients with mastocytosis. NSAIDs can be administered safely to most
      patients with mastocytosis. Extra caution should be taken in patients with a
      history of hypersensitivity reactions to other drugs, or traditional risk factors
      for NSAID hypersensitivity.

PMID- 29569285
TI  - The dimerization of PSGL-1 is driven by the transmembrane domain via a leucine
      zipper motif.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) is a homodimeric mucin ligand that is
      important to mediate the earliest adhesive event during an inflammatory response
      by rapidly forming and dissociating the selectin-ligand adhesive bonds. Recent
      research indicates that the noncovalent associations between the PSGL-1
      transmembrane domains (TMDs) can substitute for the C320-dependent covalent bond
      to mediate the dimerization of PSGL-1. In this article, we combined TOXCAT assays
      and molecular dynamics (MD) simulations to probe the mechanism of PSGL-1
      dimerization. The results of TOXCAT assays and Martini coarse-grained molecular
      dynamics (CG MD) simulations demonstrated that PSGL-1 TMDs strongly dimerized in
      a natural membrane and a leucine zipper motif was responsible for the noncovalent
      dimerization of PSGL-1 TMD since mutations of the residues that occupied a or d
      positions in an (abcdefg)n leucine heptad repeat motif significantly reduced the
      dimer activity. Furthermore, we studied the effects of the disulfide bond on the
      PSGL-1 dimer using MD simulations. The disulfide bond was critical to form the
      leucine zipper structure, by which the disulfide bond further improved the
      stability of the PSGL-1 dimer. These findings provide insights to understand the
      transmembrane association of PSGL-1 that is an important structural basis for
      PSGL-1 preferentially binding to P-selectin to achieve its biochemical and
      biophysical functions.

PMID- 29569286
TI  - Real-life experiences of people with transient ischaemic attack or minor stroke:
      A qualitative literature review.
AB  - AIMS AND OBJECTIVES: To explore and present findings of qualitative studies
      exploring real-life experiences of people with transient ischaemic attack or
      minor stroke. BACKGROUND: Transient ischaemic attack and minor stroke
      significantly increase the risk of stroke. Primarily, literature has examined
      healthcare pathways, patient outcomes and models of care through quantitative
      methodologies. Several studies have explored patient experiences using
      qualitative approaches. However, these findings have not been systematically
      collated or critically appraised to better understand the experiences of this
      population. DESIGN: A literature review of the qualitative evidence. METHOD: A
      systematic literature search was conducted in CINAHL, MEDLINE, EMBASE and
      PsycINFO between January 2005-October 2016 to identify qualitative studies that
      explored real-life experiences of people with transient ischaemic attack or minor
      stroke. The relevant EQUATOR guidelines were followed. Findings of relevant
      studies were critically appraised and collated using a thematic approach.
      RESULTS: The search retrieved 709 articles. Twelve articles were included after
      critical review. Three themes emerged including recognition, awareness and
      action; the vulnerable self; and social and personal life change. Participants
      experienced ongoing vulnerability and change in their personal and social lives.
      Specifically, people believed that their condition did not reflect their physical
      appearance and led to their needs being unmet by health professionals.
      CONCLUSIONS: This is the first review of the literature to collate the thoughts,
      perspectives and experiences of people living with transient ischaemic attack or
      minor stroke. They reveal a complex, life-altering experience characterised by
      vulnerability, instability and change. Education that assists clinicians to
      connect with these experiences may alleviate the patient-reported disconnection
      with health professionals. RELEVANCE TO CLINICAL PRACTICE: Physical and
      psychosocial dysfunctions were consistently reported to be overlooked or
      undetected by clinicians. Educating clinicians might enable them to better
      understand patient experiences, improve therapeutic interactions and meet the
      needs of this population.

PMID- 29569288
TI  - Dr Annmarie Hedges-an appreciation.

PMID- 29569287
TI  - What Remains Unexplained about the Properties of Halide Perovskites?
AB  - The notion that halide perovskite crystals (ABX3 , where X is a halide) exhibit
      unique structural and optoelectronic behavior deserves serious scrutiny. After
      decades of steady and half a decade of intense research, the question which
      attributes of these materials are unusual, is discussed, with an emphasis on the
      identification of the most important remaining issues. The goal is to stimulate
      discussion rather than to merely present a community consensus.

PMID- 29569289
TI  - Increased uptake on 18 F-fluorodeoxyglucose positron emission tomography/computed
      tomography is indicative of occult skin lesions in a patient with intravascular
      large B-cell lymphoma.

PMID- 29569290
TI  - The genetic variance but not the genetic covariance of life-history traits
      changes towards the north in a time-constrained insect.
AB  - Seasonal time constraints are usually stronger at higher than lower latitudes and
      can exert strong selection on life-history traits and the correlations among
      these traits. To predict the response of life-history traits to environmental
      change along a latitudinal gradient, information must be obtained about genetic
      variance in traits and also genetic correlation between traits, that is the
      genetic variance-covariance matrix, G. Here, we estimated G for key life-history
      traits in an obligate univoltine damselfly that faces seasonal time constraints.
      We exposed populations to simulated native temperatures and photoperiods and
      common garden environmental conditions in a laboratory set-up. Despite
      differences in genetic variance in these traits between populations (lower
      variance at northern latitudes), there was no evidence for latitude-specific
      covariance of the life-history traits. At simulated native conditions, all
      populations showed strong genetic and phenotypic correlations between traits that
      shaped growth and development. The variance-covariance matrix changed
      considerably when populations were exposed to common garden conditions compared
      with the simulated natural conditions, showing the importance of environmentally
      induced changes in multivariate genetic structure. Our results highlight the
      importance of estimating variance-covariance matrixes in environments that mimic
      selection pressures and not only trait variances or mean trait values in common
      garden conditions for understanding the trait evolution across populations and
      environments.

PMID- 29569291
TI  - In vitro efficacy of a honey-based gel against canine clinical isolates of
      Staphylococcus pseudintermedius and Malassezia pachydermatis.
AB  - BACKGROUND: Staphylococcus pseudintermedius and Malassezia pachydermatis are
      important agents in canine pyoderma and otitis. HYPOTHESIS/OBJECTIVES: Determine
      the in vitro efficacy of a honey-based gel (HBO) against meticillin-susceptible
      S. pseudintermedius (MSSP), meticillin-resistant S. pseudintermedius (MRSP) and
      M. pachydermatis, by minimum bactericidal concentration (MBC), minimum fungicidal
      concentration (MFC) and time-kill assay (TKA). Efficacy of the product's honey
      component (HO) also was evaluated. METHODS: Sixty S. pseudintermedius and 10 M.
      pachydermatis canine isolates were selected. All isolates were tested against
      serial dilutions of an HBO containing 40% HO (40%, 20%, 10%, 5% and 2.5% w/v) and
      HO alone (undiluted, 40%, 20%, 10%, 5% and 2.5% w/v). Microbroth assay followed
      by subculture was used to determine MBC and MFC. The same protocol was applied
      after product exposure to catalase. A well-diffusion assay for S.
      pseudintermedius was used to generate inhibition zones. A TKA for 10 isolates of
      S. pseudintermedius and 10 isolates of M. pachydermatis was performed. RESULTS:
      MBC was 20% w/v (5-20% w/v) for HBO and HO. HBO had lower MBC values when
      compared to HO (P = 0.003). No statistical difference was observed between
      MSSP/MRSP isolates (HBO P = 0.757, HO P = 0.743). Only HO was affected by
      catalase (P = 0.015). MFC for HBO was 10% w/v (5-10% w/v) and 40% w/v for HO (20
      >=40% w/v). All isolates were killed after 4 h of exposure. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Staphylococcus pseudintermedius and M. pachydermatis are
      susceptible to the HBO and these results can be used for future clinical trials.

PMID- 29569292
TI  - Effect of spatial connectivity on host resistance in a highly fragmented natural
      pathosystem.
AB  - Both theory and experimental evolution studies predict migration to influence the
      outcome of antagonistic coevolution between hosts and their parasites, with
      higher migration rates leading to increased diversity and evolutionary potential.
      Migration rates are expected to vary in spatially structured natural
      pathosystems, yet how spatial structure generates variation in coevolutionary
      trajectories across populations occupying the same landscape has not been tested.
      Here, we studied the effect of spatial connectivity on host evolutionary
      potential in a natural pathosystem characterized by a stable Plantago lanceolata
      host network and a highly dynamic Podosphaera plantaginis parasite
      metapopulation. We designed a large inoculation experiment to test resistance of
      five isolated and five well-connected host populations against sympatric and
      allopatric pathogen strains, over 4 years. Contrary to our expectations, we did
      not find consistently higher resistance against sympatric pathogen strains in the
      well-connected populations. Instead, host local adaptation varied considerably
      among populations and through time with greater fluctuations observed in the well
      connected populations. Jointly, our results suggest that in populations where
      pathogens have successfully established, they have the upper hand in the
      coevolutionary arms race, but hosts may be better able to respond to pathogen
      imposed selection in the well-connected than in the isolated populations. Hence,
      the ongoing and extensive fragmentation of natural habitats may increase
      vulnerability to diseases.

PMID- 29569293
TI  - Peripheral giant cell granuloma: An updated analysis of 2824 cases reported in
      the literature.
AB  - OBJECTIVE: To integrate the available data published on peripheral giant cell
      granuloma (PGCG) into a comprehensive analysis of its clinical/radiological
      features. MATERIALS AND METHODS: An electronic search was undertaken in January
      2018 in 5 databases, looking for publications reporting cases of PGCGs.
      Probability of recurrence was calculated for some variables. RESULTS: A total of
      165 publications were included, 2824 lesions identified. PGCGs were slightly more
      prevalent in women and more prevalent in mandibles, usually asymptomatic, and
      presenting erosion of the subjacent bone in almost one-third of cases. Additional
      curettage (2.8%) or peripheral osteotomy (0%) after excision presented lower
      recurrence rates in comparison with excision alone (16%). Excision followed by
      curettage decreases the probability of recurrence by 85% in comparison with
      excision alone. Other factors (age, lesion size, follow-up, gender, location,
      clinical symptoms, bone erosion) seem to do not influence the probability of
      recurrence. CONCLUSIONS: As surgical excision alone shows a considerable
      recurrence rate, excision followed by an additional therapy-curettage or
      peripheral osteotomy-should be the first choice of treatment of PGCG.

PMID- 29569294
TI  - Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and
      trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO
      AML) and review of the literature.
AB  - The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but
      has been described in up to 30% of acute myeloid leukemia (AML) in children <2
      years and associated with a poor prognosis. We present the clinical and
      cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature
      review identified 35 patients with this translocation, published between 2000 and
      2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for
      Pediatric Hematology and Oncology) database contained 651 patients with AML from
      1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present
      in patients <2 years of age (median age 6 months) but none was diagnosed as
      newborn. These patients constituted 4.3% of the patients <2 years of age. There
      was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8
      (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with
      t(7;12) and four of seven patients from the NOPHO database suffered from relapse.
      The patients with t(7;12) had a 3-year event free survival of 24% (literature)
      vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100%
      (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell
      transplantation (HSCT) in first complete remission. Relapse was frequent but the
      salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique
      subgroup of childhood AML with presentation before 2 years of age with most cases
      being associated with +19.

PMID- 29569296
TI  - Exacerbation of atopic dermatitis symptoms by ustekinumab in psoriatic patients
      with elevated serum immunoglobulin E levels: Report of two cases.
AB  - Psoriasis is a chronic inflammatory skin disease mainly mediated by a T-helper
      cell subset, Th17 cells. Recently, increased levels of total serum immunoglobulin
      (Ig)E have been reported in a subset of psoriatic patients. Ustekinumab (UST) is
      one of the most commonly used biologic agents for the treatment of moderate to
      severe plaque psoriasis, and a previous report also documented effectiveness of
      UST for psoriatic patients with high serum IgE levels. We experienced two
      psoriatic patients with high serum IgE levels, in whom UST completely improved
      psoriasis but paradoxically provoked or exacerbated atopic dermatitis (AD)-like
      symptoms. This reciprocal phenomenon suggests the shift of Th balance toward Th2,
      along with altered profiles of inflammatory cytokines. It appears prudent to
      consider the possibility of such adverse effects when treating psoriatic patients
      with UST with concomitant AD symptoms, a history of AD or high serum IgE levels.

PMID- 29569297
TI  - Maternal virus infections in pregnancy and type 1 diabetes in their offspring:
      Systematic review and meta-analysis of observational studies.
AB  - Virus infections are implicated in the development of type 1 diabetes based on
      epidemiological, clinical, in vitro cell-based and molecular studies, and animal
      models. We reviewed the association between virus infections in pregnant women
      and development of islet autoimmunity or type 1 diabetes in their offspring. We
      performed a systematic review and meta-analysis, analysed using random effects
      models, of human studies from Medline and EMBASE without language restriction.
      Inclusion criteria were as follows: cohort and case-control studies measuring
      viral nucleic acid in blood, stool, urine, or tissue, or serological tests for
      viruses, in pregnant women whose offspring developed islet autoimmunity and/or
      type 1 diabetes. All studies required sufficient data to calculate odds ratios
      and 95% confidence intervals. The 10 studies (4 case control, 6 nested-case
      control) that met the eligibility criteria included 2992 participants (953
      offspring, 2039 mothers), with varying study design. The 2 outcomes examined were
      islet autoimmunity (n = 466) and type 1 diabetes (n = 2526). Meta-analysis showed
      a significant association between virus infection during pregnancy and clinical
      type 1 diabetes during childhood (odds ratio 2.16, 95% CI 1.22-3.80; P = 0.008;
      heterogeneity X2  = 1.65, I2  = 40%), but no association with islet autoimmunity
      (1.45, 0.63-3.31; P = 0.38; X2  = 1.34, I2  = 25%). The increased risk of type 1
      diabetes following maternal virus infection is consistent with viraemia involving
      the fetus during pregnancy and suggests a potential causative link between
      antenatal infection and type 1 diabetes. Larger prospective birth studies with
      more frequent sampling, and pathogenesis studies, are required to more clearly
      establish an aetiological link.

PMID- 29569298
TI  - Reconfigurable Diodes Based on Vertical WSe2 Transistors with van der Waals
      Bonded Contacts.
AB  - New device concepts can increase the functionality of scaled electronic devices,
      with reconfigurable diodes allowing the design of more compact logic gates being
      one of the examples. In recent years, there has been significant interest in
      creating reconfigurable diodes based on ultrathin transition metal dichalcogenide
      crystals due to their unique combination of gate-tunable charge carriers, high
      mobility, and sizeable band gap. Thanks to their large surface areas, these
      devices are constructed under planar geometry and the device characteristics are
      controlled by electrostatic gating through rather complex two independent local
      gates or ionic-liquid gating. In this work, similar reconfigurable diode action
      is demonstrated in a WSe2 transistor by only utilizing van der Waals bonded
      graphene and Co/h-BN contacts. Toward this, first the charge injection
      efficiencies into WSe2 by graphene and Co/h-BN contacts are characterized. While
      Co/h-BN contact results in nearly Schottky-barrier-free charge injection,
      graphene/WSe2 interface has an average barrier height of ~80 meV. By taking the
      advantage of the electrostatic transparency of graphene and the different work
      function values of graphene and Co/h-BN, vertical devices are constructed where
      different gate-tunable diode actions are demonstrated. This architecture reveals
      the opportunities for exploring new device concepts.

PMID- 29569295
TI  - Daily allergic multimorbidity in rhinitis using mobile technology: A novel
      concept of the MASK study.
AB  - BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data
      exist about the daily dynamics of symptoms and their impact on work. To better
      understand this, we aimed to assess the presence and control of daily allergic
      multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work
      productivity using a mobile technology, the Allergy Diary. METHODS: We undertook
      a 1-year prospective observational study in which 4 210 users and 32 585 days
      were monitored in 19 countries. Five visual analogue scales (VAS) assessed the
      daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and
      work). Visual analogue scale levels <20/100 were categorized as "Low" burden and
      VAS levels >=50/100 as "High" burden. RESULTS: Visual analogue scales global
      measured levels assessing the global control of the allergic disease were
      significantly associated with allergic multimorbidity. Eight hypothesis-driven
      patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days
      of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9%
      days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a
      Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High
      Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the
      greatest impact on uncontrolled VAS global measured and impaired work
      productivity. Work productivity was significantly correlated with VAS global
      measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with
      mobile technology, we found considerable intra-individual variability of allergic
      multimorbidity including a previously unrecognized extreme pattern of
      uncontrolled multimorbidity.

PMID- 29569299
TI  - Digit identity influences numerical estimation in children and adults.
AB  - Learning the meanings of Arabic numerals involves mapping the number symbols to
      mental representations of their corresponding, approximate numerical quantities.
      It is often assumed that performance on numerical tasks, such as number line
      estimation (NLE), is primarily driven by translating from a presented numeral to
      a mental representation of its overall magnitude. Part of this assumption is that
      the overall numerical magnitude of the presented numeral, not the specific digits
      that comprise it, is what matters for task performance. Here we ask whether the
      magnitudes of the presented target numerals drive symbolic number line
      performance, or whether specific digits influence estimates. If the former is
      true, estimates of numerals with very similar magnitudes but different hundreds
      digits (such as 399 and 402) should be placed in similar locations. However, if
      the latter is true, these placements will differ significantly. In two studies (N
      = 262), children aged 7-11 and adults completed 0-1000 NLE tasks with target
      values drawn from a set of paired numerals that fell on either side of "Hundreds"
      boundaries (e.g., 698 and 701) and "Fifties" boundaries (e.g., 749 and 752).
      Study 1 used an atypical speeded NLE task, while Study 2 used a standard non
      speeded NLE task. Under both speeded and non-speeded conditions, specific
      hundreds digits in the target numerals exerted a strong influence on estimates,
      with large effect sizes at all ages, showing that the magnitudes of target
      numerals are not the primary influence shaping children's or adults' placements.
      We discuss patterns of developmental change and individual difference revealed by
      planned and exploratory analyses.

PMID- 29569300
TI  - Roles of three FurA paralogs in the regulation of genes pertaining to peroxide
      defense in Mycobacterium smegmatis mc2 155.
AB  - Mycobacterium smegmatis mc2 155 has three genes (MSMEG_6383, furA1; MSMEG_3460,
      furA2; MSMEG_6253, furA3) encoding FurA (ferric-uptake regulator A) paralogs.
      Three FurA paralogs in M. smegmatis are functionally redundant and negatively
      regulate expression of a subset of genes involved in peroxide detoxification such
      as ahpC, katG1 and katG2, as well as their own genes. The FurA paralogs sense H2
      O2 via metal-catalyzed His oxidation (MCHO) in the same way as PerR. The
      propensity of FurA2 and FurA3 for MCHO is greater than that of FurA1. The three
      furA genes are transcribed into leaderless mRNAs lacking the Shine-Dalgarno (SD)
      sequence. FurA1 and FurA3 have the quaternary structure of homodimers like most
      Fur homologs, whereas FurA2 occurs as a monomer. The monomeric structure of FurA2
      is determined by the C-terminal region of its dimerization domain. FurA2 monomers
      appear to cooperatively bind to the FurA-binding site with an inverted repeat
      configuration and have a broader binding specificity for the target DNA than
      dimeric FurA1 and FurA3. Comparative transcriptomic analysis revealed that the
      FurA paralogs do not regulate genes related to iron homeostasis in M. smegmatis,
      and that expression of SigF-regulated genes is significantly decreased in a furA
      triple mutant relative to the wild-type strain of M. smegmatis.

PMID- 29569301
TI  - Nongrowing season methane emissions-a significant component of annual emissions
      across northern ecosystems.
AB  - Wetlands are the single largest natural source of atmospheric methane (CH4 ), a
      greenhouse gas, and occur extensively in the northern hemisphere. Large
      discrepancies remain between "bottom-up" and "top-down" estimates of northern CH4
      emissions. To explore whether these discrepancies are due to poor representation
      of nongrowing season CH4 emissions, we synthesized nongrowing season and annual
      CH4 flux measurements from temperate, boreal, and tundra wetlands and uplands.
      Median nongrowing season wetland emissions ranged from 0.9 g/m2 in bogs to 5.2
      g/m2 in marshes and were dependent on moisture, vegetation, and permafrost.
      Annual wetland emissions ranged from 0.9 g m-2  year-1 in tundra bogs to 78 g m-2
      year-1 in temperate marshes. Uplands varied from CH4 sinks to CH4 sources with a
      median annual flux of 0.0 +/- 0.2 g m-2  year-1 . The measured fraction of annual
      CH4 emissions during the nongrowing season (observed: 13% to 47%) was
      significantly larger than that was predicted by two process-based model
      ensembles, especially between 40 degrees  and 60 degrees N (modeled: 4% to 17%).
      Constraining the model ensembles with the measured nongrowing fraction increased
      total nongrowing season and annual CH4 emissions. Using this constraint, the
      modeled nongrowing season wetland CH4 flux from >40 degrees  north was 6.1 +/-
      1.5 Tg/year, three times greater than the nongrowing season emissions of the
      unconstrained model ensemble. The annual wetland CH4 flux was 37 +/- 7 Tg/year
      from the data-constrained model ensemble, 25% larger than the unconstrained
      ensemble. Considering nongrowing season processes is critical for accurately
      estimating CH4 emissions from high-latitude ecosystems, and necessary for
      constraining the role of wetland emissions in a warming climate.

PMID- 29569302
TI  - Extraintestinal manifestations were common in children with coeliac disease and
      were more prevalent in patients with more severe clinical and histological
      presentation.
AB  - AIM: This study investigated the prevalence of extraintestinal manifestations
      (EIM) in paediatric coeliac disease and their associations with other disease
      features. METHODS: Researchers at the University of Tampere, Finland, compared
      EIM in 511 children diagnosed with coeliac disease from 2003 to 2014 and 180
      diagnosed with functional gastrointestinal disorders from 2007 to 2013. Disease
      severity and dietary responses were also compared between coeliac children
      diagnosed by screening (n = 146) or because of EIM (n = 116) or gastrointestinal
      symptoms (n = 249). RESULTS: Coeliac patients had more EIM (62%) than those with
      functional disorders (33%). The most common EIM in coeliac children were poor
      growth (27%) and anaemia (18%). Children with coeliac disease often showed
      fatigue (8%) and symptoms affecting the skin (15%), nervous system (9%) and
      joints (6%). Coeliac patients with EIM as their main clinical presentation had
      more severe symptoms and histological damage at diagnosis than those with
      gastrointestinal presentation and screen-detected cases. The subgroups did not
      differ with regard to other clinical and laboratory parameters and dietary
      adherence. Concomitant EIM were also common in children diagnosed because of
      gastrointestinal presentation (60%) and by screening (37%). CONCLUSION: EIM were
      common in coeliac disease and associated with more severe clinical and
      histological presentation.

PMID- 29569303
TI  - Photodynamic inactivation of Listeria innocua biofilms with food-grade
      photosensitizers: a curcumin-rich extract of Curcuma longa vs commercial
      curcumin.
AB  - AIMS: The aim of this work is to assess the potential of curcumin in the
      photosensitization of biofilms of Listeria. METHODS AND RESULTS: Biofilms of
      Listeria innocua, were irradiated with blue light in the presence of a curcumin
      rich extract of Curcuma longa or commercial curcumin. Similar experiments were
      conducted with planktonic cells, for comparison. A reduction of 4.9 log in the
      concentration of viable biofilm cells was obtained with 3.7 mg l-1 of commercial
      curcumin. Planktonic cells were much more susceptible (6.1 log reduction). A
      tetracationic porphyrin, used as a reference photosensitizer (PS), caused a very
      modest inactivation of the biofilm (1.1 log) and complete inactivation of the
      planktonic form (>8 log). CONCLUSIONS: Curcumin is an effective PS for the
      photodynamic control of Listeria biofilms and the inactivation efficiency
      attained with this natural compound is higher than with the porphyrin. This
      result may point to a better performance of type I PSs against bacterial biofilms
      by circumventing the limitations to singlet-oxygen diffusion imposed by the
      extracellular matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: Curcumin represents a
      promising alternative to the control of bacteria and bacterial biofilms in food
      products particularly in the case of meat products in which turmeric is used as
      spice.

PMID- 29569304
TI  - Phenotypic and functional alterations of myeloid-derived suppressor cells during
      the disease course of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous
      system involving dysregulated encephalitogenic T cells. Myeloid-derived
      suppressor cells (MDSCs) have been recognized for their important function in
      regulating T-cell responses. Recent studies have indicated a role for MDSCs in
      autoimmune diseases, but their significance in MS is not clear. Here, we assessed
      the frequencies of CD14+ HLA-DRlow monocytic MDSCs (Mo-MDSCs) and CD33+ CD15+
      CD11b+ HLA-DRlow granulocytic MDSCs (Gr-MDSCs) and investigated phenotypic and
      functional differences of Mo-MDSCs at different clinical stages of MS and in
      healthy subjects (HC). Increased frequencies of Mo-MDSCs (P < 0.05) and Gr-MDSCs
      (P < 0.05) were observed in relapsing-remitting MS patients during relapse (RRMS
      relapse) compared to stable RRMS (RRMS-rem). Secondary progressive MS (SPMS)
      patients displayed a decreased frequency of Mo-MDSCs and Gr-MDSCs compared to HC
      (P < 0.05). Mo-MDSCs within RRMS patients expressed significantly higher cell
      surface protein levels of CD86 and CD163 compared to SPMS patients. Mo-MDSCs
      within SPMS exhibited decreased mRNA expression of interleukin-10 and heme
      oxygenase 1 compared to RRMS and HC. Analysis of T-cell regulatory function of Mo
      MDSCs demonstrated T-cell suppressive capacity in RRMS and HCs, while Mo-MDSCs of
      SPMS promoted autologous T-cell proliferation, which aligned with a differential
      cytokine profile compared to RRMS and HCs. This study is the first to show
      phenotypic and functional shifts of MDSCs between clinical stages of MS,
      suggesting a role for MDSCs as a therapeutic target to prevent MS disease
      progression.

PMID- 29569305
TI  - Enzymatic activities and pathogenesis-related genes expression in sunflower
      inbred lines affected by Sclerotinia sclerotiorum culture filtrate.
AB  - AIMS: Studying biochemical responses and pathogenesis-related gene expression in
      sunflower-Sclerotinia interaction can shed light on factors participating to
      disease resistance. METHODS AND RESULTS: Partially resistant and susceptible
      lines were exposed to pathogen culture filtrate. The activity of antioxidant
      enzymes and proline was much more pronounced in partially resistant line. The
      more resistant to Sclerotinia sclerotiorum, the less (1,4)-beta-glucanase
      activity was observed. PDF 1.2 and PR5-1 exhibited higher transcript abundance in
      the partially resistant line than in the susceptible line. CONCLUSIONS:
      Considering the dual roles of oxalic acid, activation of the antioxidant system
      in partially resistant line might lead to suppression of oxidative burst which is
      beneficial for the growth of fungus at later stages of infection. The ability of
      the partially resistant line in balancing antioxidant enzymes could reserve H2 O2
      as a substrate for peroxidase that might lead to lignification. The contribution
      of (1,4)-beta-glucanase defence responses against Sclerotinia was observed. The
      roles of SA and JA marker genes were demonstrated in sunflower defence responses.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The time of antioxidant system activation
      in host is important in order to contribute to defence responses. To date, the
      changes in the expression of PR1 and PDF 1.2 and contribution of (1,4)-beta
      glucanase enzyme in sunflower defence responses were not reported in previous
      studies.

PMID- 29569307
TI  - Stereoselective Synthesis of 2-Deoxyglycosides from Glycals by Visible-Light
      Induced Photoacid Catalysis.
AB  - The direct, photoacid-catalyzed synthesis of 2-deoxyglycosides from glycals is
      reported. A series of phenol-conjugated acridinium-based organic photoacids were
      rationally designed, synthesized, and studied alongside the commercially
      available phenolic catalyst eosin Y. In the presence of such a photoacid catalyst
      and light, synthetic glycals were activated and coupled with a range of alcohols
      to afford 2-deoxyglycosides in good yields and with excellent alpha-selectivity.

PMID- 29569306
TI  - Optogenetic Control of Voltage-Gated Calcium Channels.
AB  - Voltage-gated Ca2+ (CaV ) channels mediate Ca2+ entry into excitable cells to
      regulate a myriad of cellular events following membrane depolarization. We report
      the engineering of RGK GTPases, a class of genetically encoded CaV channel
      modulators, to enable photo-tunable modulation of CaV channel activity in
      excitable mammalian cells. This optogenetic tool (designated optoRGK) tailored
      for CaV channels could find broad applications in interrogating a wide range of
      CaV -mediated physiological processes.

PMID- 29569308
TI  - Cutaneous leishmaniasis caused by Leishmania tropica in Israel.

PMID- 29569309
TI  - Patterns of reproductive isolation in a haplodiploid - strong post-mating,
      prezygotic barriers among three forms of a social spider mite.
AB  - In speciation research, much attention is paid to the evolution of reproductive
      barriers, preventing diverging groups from hybridizing back into one gene pool.
      The prevalent view is that reproductive barriers evolve gradually as a by-product
      of genetic changes accumulated by natural selection and genetic drift in groups
      that are segregated spatially and/or temporally. Reproductive barriers, however,
      can also be reinforced by natural selection against maladaptive hybridization.
      These mutually compatible theories are both empirically supported by studies,
      analysing relationships between intensity of reproductive isolation and genetic
      distance in sympatric taxa and allopatric taxa. Here, we present the - to our
      knowledge - first comparative study in a haplodiploid organism, the social spider
      mite Stigmaeopsis miscanthi, by measuring premating and post-mating, pre- and
      post-zygotic components of reproductive isolation, using three recently diverged
      forms of the mite that partly overlap in home range. We carried out cross
      experiments and measured genetic distances (mitochondrial DNA and nuclear DNA)
      among parapatric and allopatric populations of the three forms. Our results show
      that the three forms are reproductively isolated, despite the absence of
      premating barriers, and that the post-mating, prezygotic component contributes
      most to reproductive isolation. As expected, the strength of post-mating
      reproductive barriers positively correlated with genetic distance. We did not
      find a clear pattern of prezygotic barriers evolving faster in parapatry than in
      allopatry, although one form did show a trend in line with the ecological and
      behavioural relationships between the forms. Our study advocates the versatility
      of haplodiploid animals for investigating the evolution of reproductive barriers.

PMID- 29569310
TI  - Molecular model for neuroendocrine prostate cancer progression.
AB  - Prostate cancer (PCa) is the most common form of cancer in men in the developed
      world and the second leading cause of cancer-related deaths. While advanced PCa
      is initially controlled with hormonal therapies targeting the androgen receptor
      (AR) pathway, recurrence occurs because of the emergence of lethal castration
      resistant PCa (CRPC). Despite newer AR pathway inhibitors that prolong survival,
      resistance still emerges, most often with rising PSA levels indicative of AR
      driven activity, but increasingly as non-AR-driven cancer. Treatment resistance
      mechanisms include AR-signalling pathway alterations, AR-signalling bypass
      mechanisms, and AR-independent clonal evolution. The latter mechanism can lead to
      the emergence of neuroendocrine prostate cancer (NEPC), an aggressive lethal
      subtype of PCa. The incidence of treatment-induced NEPC is rising because of the
      widespread use of more potent AR pathway inhibitors. This comprehensive review of
      major NEPC drivers and facilitators defines three coordinated processes
      contributing to NEPC progression. Specifically, castration-resistant
      adenocarcinoma cells gain lineage plasticity under selective pressures of potent
      AR suppression to transform into AR-independent tumour cells. In concert,
      neuroendocrine (NE)-specific transdifferentiation factors induce NE lineage of
      these PCa cells, which, with support of increased proliferation factors,
      contributes to clonal expansion and tumour repopulation into NEPC. We examine the
      roles of each of the major NEPC contributors during the disease progression and
      identify potential therapeutic opportunities for targeted therapies.

PMID- 29569311
TI  - Initial series of magnetic resonance imaging (MRI)-fusion targeted prostate
      biopsy using the first transperineal targeted platform available in the USA.
AB  - OBJECTIVES: To describe a step-by-step guide for using the first transperineal
      targeted prostate biopsy platform available in the USA. PATIENTS AND METHODS: A
      total of 32 men with elevated prostate-specific antigen (PSA) levels were
      diagnosed with a region of interest on multiparametric magnetic resonance imaging
      (mpMRI) between February 2017 and January 2018. The transperineal targeted
      prostate biopsy procedure was accomplished via a transperineal approach and used
      a stepper, combined with advanced mpMRI/transrectal ultrasound fusion software,
      to perform targeted prostate biopsy. The detection of overall and clinically
      significant prostate cancer (PCa) was assessed as well as the rate of
      complications. RESULTS: The median patient age was 68.0 years and the median PSA
      was 8.0 ng/mL. Two patients (6%) were active surveillance candidates and 16 (50%)
      had a prior negative prostate biopsy. The detection rates for overall and
      clinically significant PCa were 81% and 59%, respectively. The two candidates for
      active surveillance and eight of the patients with a prior negative prostate
      biopsy had clinically significant PCa confirmed on targeted biopsy. There were no
      peri-operative complications. CONCLUSION: These results demonstrate the promising
      potential of the first transperineal targeted prostate biopsy platform in the USA
      as an alternative diagnostic method for PCa.

PMID- 29569312
TI  - Substance-use initiation moderates the effect of stress on white-matter
      microstructure in adolescents.
AB  - BACKGROUND: While childhood stress may contribute risk to substance-use
      initiation and differences in brain white-matter development, understanding of
      the potential impact of substance-use initiation on the relationship between
      experienced stress and white-matter microstructure remains limited. OBJECTIVES:
      This study examined whether substance-use initiation moderated the effect of
      perceived stress on white-matter differences using measures of primary white
      matter fiber anisotropy. METHODS: Forty adolescents (age 14.75 +/- .87 years)
      were assessed on the Perceived Stress Scale, and 50% were determined to have
      presence of substance-use initiation. White-matter microstructure was examined
      using primary-fiber orientations anisotropy, which may reflect white-matter
      integrity, modeled separately from other fiber orientations in the same voxels.
      Analyses were conducted on regions of interest previously associated with
      childhood stress and substance use. RESULTS: Lower perceived stress and presence
      of substance-use initiation were related to greater right cingulum primary-fiber
      measures. Substance-use-initiation status moderated the association between
      perceived stress and right cingulum primary-fiber measures, such that higher
      perceived stress was associated with lower right cingulum primary-fiber
      anisotropy in adolescents without substance-use initiation, but not in those with
      substance-use initiation. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings in
      primary-fiber anisotropy suggest differences in right cingulum white-matter
      integrity is associated with substance-use initiation in higher-stress
      adolescents. This reflects a possible pre-existing risk factor, an impact of
      early substance use, or a combination thereof. Examination of potential markers
      associated with substance-use initiation in white-matter microstructure among
      stress-exposed youth warrant additional investigation as such biomarkers may
      inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224).

PMID- 29569313
TI  - Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese
      patients with type 2 diabetes mellitus: A case control study.
AB  - AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking
      surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity
      associated type 2 diabetes mellitus. This analysis was conducted to evaluate the
      efficacy and safety of the DJBL in comparison to lifestyle changes and
      antidiabetic drugs. MATERIALS AND METHODS: To determine the efficacy and long
      term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes
      mellitus from the German DJBL registry were analysed. For comparison with
      standard treatment, propensity-score-matching with patients from the German DPV
      registry, including the matching parameters sex, age, diabetes duration, baseline
      BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111
      patients in the DJBL group and 222 matched control DPV patients. RESULTS: Mean
      treatment time with the DJBL was 47.5 +/- 12.2 weeks, mean BMI reduction was 5.0
      kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001).
      Reduction of antidiabetic medications and improvements in other metabolic and
      cardiovascular risk parameters was observed. In comparison to the matched control
      group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P <
      .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly
      higher. Total cholesterol, LDL cholesterol and blood pressure were also
      significantly better. CONCLUSION: This study provides the largest, so far,
      hypothesis-generating evidence for a putative positive risk/benefit ratio for
      treatment of obese patients with type 2 diabetes mellitus with the DJBL as an
      alternative treatment option for this patient population.

PMID- 29569315
TI  - Coordination-Driven Self-Assembly of a Molecular Knot Comprising Sixteen
      Crossings.
AB  - Molecular knots have become highly attractive to chemists because of their
      prospective properties in mimicking biomolecules and machines. Only a few
      examples of molecular knots from the billions tabulated by mathematicians have
      been realized and molecular knots with more than eight crossings have not been
      reported to date. We report here the coordination-driven [8+8] self-assembly of a
      higher-generation molecular knot comprising as many as sixteen crossings. Its
      solid-state X-ray crystal structure and multinuclear 2D NMR findings confirmed
      its architecture and topology. The formation of this molecular knot appears to
      depend on the functionalities and geometries of donor and acceptor in terms of
      generating appropriate angles and strong pi-pi interactions supported by
      hydrophobic effects. This study shows coordination-driven self-assembly offers a
      powerful potential means of synthesizing more and more complicated molecular
      knots and of understanding differences between the properties of knotted and
      unknotted structures.

PMID- 29569314
TI  - Synthesis and Self-Assembly of Bay-Substituted Perylene Diimide Gemini-Type
      Surfactants as Off-On Fluorescent Probes for Lipid Bilayers.
AB  - Interest in bay-substituted perylene-3,4:9,10-tetracarboxylic diimides (PDIs) for
      solution-based applications is growing due to their improved solubility and
      altered optical and electronic properties compared to unsubstituted PDIs.
      Synthetic routes to 1,12-bay-substituted PDIs have been very demanding due to
      issues with steric hindrance and poor regioselectivity. Here we report a simple
      one-step regioselective and high yielding synthesis of a 1,12-dihydroxylated PDI
      derivative that can subsequently be alkylated in a straightforward fashion to
      produce nonplanar 1,12-dialkoxy PDIs. These PDIs show a large Stokes shift, which
      is specifically useful for bioimaging applications. A particular cationic PDI
      gemini-type surfactant has been developed that forms nonfluorescent self
      assembled particles in water ("off state"), which exerts a high fluorescence upon
      incorporation into lipophilic bilayers ("on state"). Therefore, this probe is
      appealing as a highly sensitive fluorescent labelling marker with a low
      background signal for imaging artificial and cellular membranes.

PMID- 29569316
TI  - Improved prediction of fungal effector proteins from secretomes with EffectorP
      2.0.
AB  - Plant-pathogenic fungi secrete effector proteins to facilitate infection. We
      describe extensive improvements to EffectorP, the first machine learning
      classifier for fungal effector prediction. EffectorP 2.0 is now trained on a
      larger set of effectors and utilizes a different approach based on an ensemble of
      classifiers trained on different subsets of negative data, offering different
      views on classification. EffectorP 2.0 achieves an accuracy of 89%, compared with
      82% for EffectorP 1.0 and 59.8% for a small size classifier. Important features
      for effector prediction appear to be protein size, protein net charge as well as
      the amino acids serine and cysteine. EffectorP 2.0 decreases the number of
      predicted effectors in secretomes of fungal plant symbionts and saprophytes by
      40% when compared with EffectorP 1.0. However, EffectorP 1.0 retains value, and
      combining EffectorP 1.0 and 2.0 results in a stringent classifier with a low
      false positive rate of 9%. EffectorP 2.0 predicts significant enrichments of
      effectors in 12 of 13 sets of infection-induced proteins from diverse fungal
      pathogens, whereas a small cysteine-rich classifier detects enrichment in only
      seven of 13. EffectorP 2.0 will fast track the prioritization of high-confidence
      effector candidates for functional validation and aid in improving our
      understanding of effector biology. EffectorP 2.0 is available at
      http://effectorp.csiro.au.

PMID- 29569317
TI  - The urgency to embrace Big Data opportunities in medicine.

PMID- 29569319
TI  - Modeling the Impact of Stream Discharge Events on Riparian Solute Dynamics.
AB  - The biogeochemical composition of stream water and the surrounding riparian water
      is mainly defined by the exchange of water and solutes between the stream and the
      riparian zone. Short-term fluctuations in near stream hydraulic head gradients
      (e.g., during stream flow events) can significantly influence the extent and rate
      of exchange processes. In this study, we simulate exchanges between streams and
      their riparian zone driven by stream stage fluctuations during single stream
      discharge events of varying peak height and duration. Simulated results show that
      strong stream flow events can trigger solute mobilization in riparian soils and
      subsequent export to the stream. The timing and amount of solute export is linked
      to the shape of the discharge event. Higher peaks and increased durations
      significantly enhance solute export, however, peak height is found to be the
      dominant control for overall mass export. Mobilized solutes are transported to
      the stream in two stages (1) by return flow of stream water that was stored in
      the riparian zone during the event and (2) by vertical movement to the
      groundwater under gravity drainage from the unsaturated parts of the riparian
      zone, which lasts for significantly longer time (> 400 days) resulting in long
      tailing of bank outflows and solute mass outfluxes. We conclude that strong
      stream discharge events can mobilize and transport solutes from near stream
      riparian soils into the stream. The impact of short-term stream discharge
      variations on solute exchange may last for long times after the flow event.

PMID- 29569318
TI  - Insulin resistance is associated with smaller brain volumes in a preliminary
      study of depressed and obese children.
AB  - OBJECTIVE: During childhood, the brain can consume up to 65% of total calories,
      and a steady supply of the brain's main fuel glucose needs to be maintained.
      Although the brain itself is not dependent on insulin for the uptake of glucose,
      insulin plays an important role in energy homeostasis. Thus, the risk for insulin
      resistance during brain development may negatively impact the whole brain volume.
      METHODS: We investigated the link between the insulin resistance and the whole
      brain volume as measured by structural Magnetic resonance imaging (MRI) in 46
      unmedicated depressed and overweight youths between the ages of 9 and 17 years.
      RESULTS: Smaller whole brain volumes were associated with insulin resistance
      independent of age, sex, depression severity, body mass index, socioeconomic
      status, Tanner Stage, and Intelligence quotient (IQ) (r = 0.395, P = .014)
      CONCLUSIONS: There may be a significant cost for developing insulin resistance on
      the developing brain. Disentangling the precise relationship between the insulin
      resistance and the developing brain is critical.

PMID- 29569321
TI  - Blood pressure profile and nocturnal oxygen desaturation.

PMID- 29569320
TI  - Primary magnetic resonance imaging/ultrasonography fusion-guided biopsy of the
      prostate.
AB  - OBJECTIVE: To examine the performance of a primary magnetic resonance imaging
      (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB), and in combination
      with an added systematic biopsy (SB). PATIENTS AND METHODS: Analysis of 318
      consecutive biopsy-naive men with suspicious multiparametric MRI (mpMRI; Prostate
      Imaging Reporting and Data System [PI-RADS] score >=3) undergoing transrectal TB
      and 10-core SB between January 2012 and December 2016. The indication for
      performing mpMRI was based on clinical parameters and decided by the treating
      urologist before admission. TB was performed with a sensor-based MRI/US fusion
      guided platform. Clinically significant prostate cancer was defined as Gleason
      score >=4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP]
      grade 3) or maximum cancer core length of >=6 mm. RESULTS: A median
      (interquartile range) of 14 (13-14) biopsies per case were taken. The overall
      cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of
      prostate cancers and the SB alone detected 70%. The PI-RADS dependent CDR for the
      combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI
      RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was
      diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163
      cases (51%). The number of missed or underestimated prostate cancers with a
      Gleason score >=8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for
      SB alone in comparison with the results of the combination of TB and SB. The rate
      of insignificant prostate cancer was comparable for the combination of TB and SB
      and TB alone (50/318, 16% vs 50/318, 16%). CONCLUSIONS: Pre-biopsy mpMRI is of
      incremental value in increasing the detection of clinically significant prostate
      cancer in biopsy-naive patients with suspicion of prostate cancer. Combining TB
      with SB further improved the diagnostic accuracy without increasing the rate of
      insignificant prostate cancer.

PMID- 29569322
TI  - Uterine fibroids and risk of hypertension: Implication of inflammation and a
      possible role of the renin-angiotensin-aldosterone system.

PMID- 29569323
TI  - Real-world observational results from a database of 48 million men in the United
      States: Relationship of cardiovascular disease, diabetes mellitus and depression
      with age and erectile dysfunction.
AB  - AIMS: To evaluate the relationship of comorbidities (cardiovascular disease
      [CVD], diabetes mellitus [DM] and depression) with erectile dysfunction (ED) and
      age using real-world claims data from 48 million men in the United States.
      METHODS: This was a cross-sectional, non-interventional study in men aged >=18
      years using data from the Truven Health MarketScan(r) and Medicare Supplemental
      Research Databases from January 2010 to December 2015, with an observational
      period of January 2011 to December 2014 to allow for 12 months pre- and post
      index. Comorbidity rate was compared between ED and non-ED groups by age using
      the chi2 (bivariate) test. Comorbidity relationship to ED after controlling for
      categorical variables was assessed using logistic regression analysis. RESULTS:
      In all, 48 004 379 men were in the database. Of the 9 839 578 who met the
      inclusion criteria, 573 313 (6%) were ED patients and 9 266 265 (94%) were non-ED
      patients. ED diagnosis increased decade to decade from 18-29 years to 50-59 years
      but decreased from 60-69 years to >=90 years. ED patients had a higher prevalence
      of CVD, DM and depression than non-ED patients in all periods (P < .0001). After
      controlling for potential demographic and baseline confounders, the association
      between ED and CVD, DM and depression remained significant for each age group
      beginning at 30-39 years (P < .0001). DISCUSSION: Conversations with patients
      concerning ED should be comprehensive regardless of patient age, in particular in
      those who have CVD, DM and/or depression. CONCLUSIONS: In the real-world setting,
      ED diagnosis was associated with CVD, DM and depression across age groups,
      suggesting a need for inquiry about the potential for comorbidities among these
      men as a preventative measure against potentially serious future events.

PMID- 29569324
TI  - Distinct gene expression pathways in islets from individuals with short- and long
      duration type 1 diabetes.
AB  - AIMS: Our current understanding of the pathogenesis of type 1 diabetes (T1D)
      arose, in large part, from studies using the non-obese diabetic (NOD) mouse
      model. In the present study, we chose a human-focused method to investigate T1D
      disease mechanisms and potential targets for therapeutic intervention by directly
      analysing human donor pancreatic islets from individuals with T1D. MATERIALS AND
      METHODS: We obtained islets from a young individual with T1D for 3 years and from
      an older individual with T1D for 27 years and performed unbiased functional
      genomic analysis by high-depth RNA sequencing; the T1D islets were compared with
      islets isolated from 3 non-diabetic donors. RESULTS: The islets procured from
      these T1D donors represent a unique opportunity to identify gene expression
      changes in islets after significantly different disease duration. Data analysis
      identified several inflammatory pathways up-regulated in short-duration disease,
      which notably included many components of innate immunity. As proof of concept
      for translation, one of the pathways, governed by IL-23(p19), was selected for
      further study in NOD mice because of ongoing human trials of biologics against
      this target for different indications. A mouse monoclonal antibody directed
      against IL-23(p19) when administered to NOD mice resulted in a significant
      reduction in incidence of diabetes. CONCLUSION: While the sample size for this
      study is small, our data demonstrate that the direct analysis of human islets
      provides a greater understanding of human disease. These data, together with the
      analysis of an expanded cohort to be obtained by future collaborative efforts,
      might result in the identification of promising novel targets for translation
      into effective therapeutic interventions for human T1D, with the added benefit of
      repurposing known biologicals for use in different indications.

PMID- 29569325
TI  - Biocompatibility and hemocompatibility of efficiently decellularized whole
      porcine kidney for tissue engineering.
AB  - Whole kidney decellularization is a promising approach in regenerative medicine
      for engineering a functional organ. The reaction of the potential host depends on
      the biocompatibility of these decellularized constructs. Despite the proven
      ability of decellularized kidney scaffolds to guide cell attachment and growth,
      little is known about biocompatibility and hemocompatibility of these scaffolds.
      Our aim is to prepare decellularized kidneys of a clinically relevant size and
      evaluate its biocompatibility and hemocompatibility. Porcine kidneys were
      cannulated via the renal artery, and then perfused with 0.1% sodium dodecyl
      sulfate solution. Hematoxylin and eosin as well as DAPI staining confirmed
      cellular clearance from native kidneys in addition to preservation of the
      microstructure. SEM confirmed the absence of any cellular content within the
      scaffold, which is maintained in a well-organized 3D architecture. Decellularized
      kidneys retained the intact renal vasculature upon examination with contrast
      radiography. The essential structural extracellular matrix molecules were well
      preserved. Scaffolds were susceptible to enzymatic degradation upon collagenase
      treatment. Scaffolds showed a good hemocompatibility when exposed to porcine
      blood. Decellularization was efficient to remove 97.7% of DNA from native kidneys
      in addition to the immunogenic and pathogenic antigens. Scaffolds did not induce
      the human immune response in vitro. Decellularized kidneys were non-cytotoxic to
      pig kidney cells (PKs). PKs were able to grow and proliferate within the
      decellularized renal scaffolds with maintaining a higher function than cells
      grown as monolayers. Thus, we have developed a rapid decellularization technique
      for generating biocompatible kidney scaffolds that represents a step toward
      development of a transplantable organ. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 2034-2047, 2018.

PMID- 29569326
TI  - In vitro and in vivo performance of methacrylated gellan gum hydrogel
      formulations for cartilage repair.
AB  - Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation
      hydrogel for controlled delivery of cartilage-forming cells into focal chondral
      lesions, allowing immediate in situ retention of cells and 3D filling of lesion
      volume, such approach deemed compatible with an arthroscopic procedure.
      Formulation optimization was carried out in vitro using chondrocytes and adipose
      mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was
      conducted using a rabbit model with induced chondral lesions. Outcomes were
      compared with microfracture or non-treated control. Three grading scores were
      used to evaluate tissue repair after 8 weeks by macroscopic, histological and
      immunohistochemical analysis. Intense collagen type II and low collagen type I
      gene and protein expression were achieved in vitro by the ASC + GGMA formulation,
      in light with development of healthy chondral tissue. In vivo, this formulation
      promoted significantly superior de novo cartilage formation compared with the non
      treated group. Maintenance of chondral height and integration with native tissue
      was further accomplished. The physicochemical properties of the proposed GGMA
      hydrogel exhibited highly favorable characteristics and biological performance
      both in vitro and in vivo, positioning itself as an attractive xeno-free
      biomaterial to be used with chondrogenic cells for a cost-effective treatment of
      focal chondral lesions. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 106A: 1987-1996, 2018.

PMID- 29569327
TI  - Reducing Emergency Room Visits and In-Hospitalizations by Implementing Best
      Practice for Transitional Care Using Innovative Technology and Big Data.
AB  - BACKGROUND: Efforts to improve care transitions require coordination across the
      healthcare continuum and interventions that enhance communication between acute
      and community settings. AIMS: To improve post-discharge utilization value using
      technology to identify high-risk individuals who might benefit from rapid nurse
      outreach to assess social and behavioral determinants of health with the goal of
      reducing inpatient and emergency department visits. METHODS: The project employed
      a before and after comparison of the intervention site with similar primary care
      practice sites using population-level Medicaid claims data. The intervention
      targeted discharged persons with preexisting chronic disease and delivered a care
      transition alert to a nurse care coordinator for immediate telephonic outreach.
      The nurse assessed social determinants of health and incorporated problems into
      the EHR to share across settings. The project evaluated health outcomes and the
      value of nursing care on existing electronic claims data to compare utilization
      in the years before and during the intervention using negative binomial
      regression to account for rare events such as inpatient visits. RESULTS: Avoiding
      readmissions and emergency visits, and increasing timely outpatient visits
      improved the individual's experience of care and the work life of healthcare
      providers, while reducing per capita costs (Quadruple Aim). In the intervention
      practice, the nurse care coordinator demonstrated the value of nursing care by
      reducing inpatient (25%) and emergency (35%) visits, and increasing outpatient
      visits (27%). The estimated value of avoided encounters over the secular Medicaid
      trend was $664 per adult with chronic disease, generating $71,289 in revenue from
      additional outpatient visits. LINKING EVIDENCE TO ACTION: Using health
      information exchange to deliver appropriate and timely evidence-based clinical
      decision support in the form of care transition alerts and assessment of social
      determinants of health, in conjunction with data science methods, demonstrates
      the value of nursing care and resulted in achieving the Quadruple Aim.

PMID- 29569328
TI  - A randomized clinical trial to evaluate the efficacy of contingency management
      for treatment of waterpipe tobacco addiction.
AB  - BACKGROUND AND OBJECTIVES: Unlike cigarette smoking cessation, waterpipe tobacco
      smoking cessation is relatively understudied. The objective of this randomized
      clinical trial was to examine the efficacy of contingency management (CM) for
      promoting initial waterpipe smoking abstinence. METHODS: The study used a two
      group, repeated measures design. Participants attended 10 visits (two visits per
      week, on Mondays and Thursdays) across 5 weeks. Thirty-nine adult waterpipe
      tobacco users who did not smoke cigarettes and were not planning on quitting
      waterpipe tobacco smoking were randomly assigned to either the contingent (n =
      19) or non-contingent (n = 20) groups. Contingent group received monetary rewards
      based on negative salivary cotinine results. Earning rewards started at $14 and
      increased by $.50 with each subsequent negative sample for a maximum $192.50. Non
      contingent group earned rewards independent of salivary cotinine results.
      Prolonged abstinence was defined as having negative salivary cotinine results for
      eight or more visits (two lapses were allowed); and 7-day point prevalence was
      defined as having negative salivary cotinine results at visit 9 and 10 (final
      week). RESULTS: The prolonged abstinence rate in the contingent and non
      contingent groups were 42.1% and 5.0%, respectively, (p = .008). The 7-day point
      prevalence in the contingent and non-contingent were 47.4% and 5.0%,
      respectively, (p = .003). DISCUSSION AND CONCLUSIONS: Rewards contingent on
      biochemically verified abstinence promote initial waterpipe tobacco cessation.
      This is useful information for consideration in future cessation programs for
      waterpipe smokers. SCIENTIFIC SIGNIFICANCE: CM strategy may have potential
      benefit in addressing waterpipe tobacco smoking in non-treatment seeking adults.
      (Am J Addict 2018;27:202-209).

PMID- 29569329
TI  - Evaluating the effectiveness of atomoxetine for the treatment of primary
      orthostatic hypotension in adults.

PMID- 29569330
TI  - Characterization of 3-Acetyl Chlorophyll a and 3-Acetyl Protochlorophyll a
      Accommodated in the B800 Binding Sites of Photosynthetic Light-Harvesting Complex
      2 in the Purple Photosynthetic Bacterium Rhodoblastus acidophilus.
AB  - We present the detailed characterization on the reconstitution of two cyclic
      tetrapyrrole pigments that have the same substituents but differ in the degree of
      hydrogenation in the macrocycles from bacteriochlorophyll (BChl) a (7,8,17,18
      tetrahydroporphyrin) into the binding sites of B800 BChl a in light-harvesting
      complex 2 (LH2) of purple photosynthetic bacteria. Both 3-acetyl chlorophyll
      (Chl) a (17,18-dihydroporphyrin) and 3-acetyl protochlorophyll (PChl) a
      (porphyrin) were inserted into the B800-binding pockets in LH2, indicating that
      these pockets allow alteration of the degree of hydrogenation in the cyclic
      tetrapyrroles. Redshifts of the Qy peak positions of 3-acetyl (P)Chl a by
      insertion into the B800-binding sites were smaller than that of BChl a. The
      relative Qy absorbance of 3-acetyl (P)Chl a to B850 BChl a in the reconstituted
      proteins was significantly smaller than that of B800 BChl a in native LH2 in
      spite of their high occupancy in the B800-binding sites. These are ascribable to
      the smaller dipole strengths of 3-acetyl (P)Chl a. We also performed the
      coreconstitution of both 3-acetyl Chl a and BChl a into the nine B800-binding
      sites in LH2, indicating that the affinity of 3-acetyl Chl a to the B800-cavity
      was slightly higher than that of BChl a.

PMID- 29569331
TI  - Mesenchymal stem cell seeded, biomimetic 3D printed scaffolds induce complete
      bridging of femoral critical sized defects.
AB  - No current clinical treatments provide an ideal long-term solution for repair of
      long bone segment defects. Incomplete healing prevents patients from returning to
      preinjury activity and ultimately requires additional surgery to induce healing.
      Obtaining autologous graft material is costly, incurs morbidity, requires
      surgical time, and quality material is finite. In this pilot study, 3D printed
      biomimetic scaffolds were used to facilitate rapid bone bridging in critical
      sized defects in a sheep model. An inverse trabecular pattern based on micro-CT
      scans of sheep trabecular bone was printed in polybutylene terephthalate.
      Scaffolds were coated with micron-sized tricalcium phosphate particles to induce
      osteoconductivity. Mesenchymal stem cells (MSCs) were isolated from sheep
      inguinal and tail fat, in one group of sheep and scaffolds were infiltrated with
      MSCs in a bioreactor. Controls did not undergo surgery for cell extraction.
      Scaffolds were implanted into two experimental and two control adult sheep, and
      followed for either 3 or 6 months. Monthly radiographs and post explant micro-CT
      scanning demonstrated bone formation on the lateral, anterior, medial, and
      posterior-medial aspects along the entire length of the defect. Bone formation
      was absent on the posterior-lateral aspect where a muscle is generally attached
      to the bone. The 3-month time point showed 15.5% more cortical bone deposition
      around the scaffold circumference while the 6-month time point showed 40.9% more
      bone deposition within scaffold pores. Control sheep failed to unite. Serum
      collagen type-1C-terminus telopeptides (CTX-1) showed time-dependent levels of
      bone resorption, and calcein labeling demonstrated an increase in bone formation
      rate in treated animals compared with controls. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29569332
TI  - The impact of coronary chronic total occlusion percutaneous coronary intervention
      upon donor vessel fractional flow reserve and instantaneous wave-free ratio:
      Implications for physiology-guided PCI in patients with CTO.
AB  - OBJECTIVE: To investigate the immediate and short term impact of right coronary
      artery (RCA) chronic total coronary occlusion (CTO) percutaneous coronary
      intervention (PCI) upon collateral donor vessel fractional flow reserve (FFR) and
      instantaneous wave-free ratio (iFR). BACKGROUND: CTO PCI influences collateral
      donor vessel physiology, making the indication and/or timing of donor vessel
      revascularization difficult to determine. METHODS: In patients with RCA CTO, FFR,
      iFR, and collateral function index (FFRcoll ) were measured in LAD and LCx pre
      CTO PCI, immediately post and at 4 month follow-up. RESULTS: 34 patients
      underwent successful PCI. In the predominant donor vessel immediately post PCI,
      FFR, and FFRcoll did not change (0.76 +/- 0.12 to 0.75 +/- 0.13, P = 0.267 and
      0.31 +/- 0.10 vs. 0.34 +/- 0.11, P = 0.078), but iFR increased significantly
      (0.86 +/- 0.10 to 0.88 +/- 0.10, P = 0.012). At follow-up, there was a
      significant increase in predominant donor FFR and iFR (0.76 +/- 0.12 to 0.79 +/-
      0.11, P = 0.047 and 0.86 +/- 0.10 to 0.90 +/- 0.07, P = 0.003), accompanied by a
      significant reduction in FFRcoll (0.31 +/- 0.10 to 0.18 +/- 0.07 P < 0.0001).
      These changes resulted in a reclassification of the predominant donor vessel from
      ischemic to nonischemic in 18% (FFR) and 25% (iFR) of the cases, respectively.
      CONCLUSIONS: Successful recanalization of an RCA CTO resulted in a modest but
      statistically significant increase in the predominant donor vessel immediately
      post CTO PCI in the case of iFR and at 4-month follow-up for FFR and iFR compared
      to pre-PCI with a concomitant reduction in collateral function.

PMID- 29569333
TI  - Vacuumed collagen-impregnated bioglass scaffolds: Characterization and influence
      on proliferation and differentiation of bone marrow stromal cells.
AB  - This study evaluated physical-chemical characteristics of a vacuumed collagen
      impregnated bioglass (BG) scaffolds and bone marrow stromal cells (BMSCs)
      behavior on those composites. scanning electron microscope and energy dispersive
      x-ray spectroscope demonstrated collagen (Col) was successfully introduced into
      BG. Vacuum impregnation system has showed efficiency for Col impregnation in BG
      scaffolds (approximately 20 wt %). Furthermore, mass weight decreasing and more
      stabilized pH were observed over time for BG/Col upon incubation in phosphate
      buffered saline compared to plain BG under same conditions. Calcium evaluation
      (Ca assay) demonstrated higher calcium uptake for BG/Col samples compared to BG.
      In addition, BG samples presented hydroxyapatite crystals formation on its
      surface after 14 days in simulated body fluid solution, and signs of initial
      degradation were observed for BG and BG/Col after 21 days. Fourier transform
      infrared spectroscopy spectra for both groups indicated peaks for hydroxyapatite
      formation. Finally, a significant increase of BMSCs viability for both composites
      was observed compared to control group, but no increase of osteogenic
      differentiation-related gene expressions were found. In summary, BG/Col scaffolds
      have improved degradation, pH equilibrium and Ca mineralization over time,
      accompanied by hydroxyapatite formation. Moreover, both BG and BG/Col scaffolds
      were biocompatible and noncytotoxic, promoting a higher cell viability compared
      to control. Future investigations should focus on additional molecular and in
      vivo studies in order to evaluate biomaterial performance for bone tissue
      engineering applications. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29569334
TI  - Determinants of Quality of Life in Lung Cancer Patients.
AB  - PURPOSE: To examine the relationships of self-care, symptoms, and a variety of
      demographic factors to quality of life (QOL), and to identify determinants of QOL
      in lung cancer patients undergoing chemotherapy. DESIGN: A cross-sectional,
      correlational study. METHODS: 159 patients with lung cancer undergoing
      chemotherapy were recruited from three southern hospitals in Taiwan. Four
      instruments were used: the Quality of Life Questionnaire Core 30-item (QLQ-C30),
      M.D. Anderson Symptom Inventory (MDASI), Memorial Symptom Assessment Scale-Short
      Form (MSAS-SF), and Self-Care Behavior Scale (SCBS). FINDINGS: Lung cancer
      patients rated lower scores of self-care behaviors on food choice and nutrition
      maintenance, regular exercise and sleep, and medical compliance. Being younger,
      having spouses as main caregivers, having food choice and nutrition maintenance,
      and getting regular exercise and sleep were associated with better QOL. Degree of
      interference with life, age, food choice and nutrition maintenance, and
      psychological symptoms were found to predict functional QOL and accounted for 43%
      of total variance. CONCLUSIONS: The findings identified factors influencing QOL
      and provided evidence for designing an intervention to enhance QOL in lung cancer
      patients undergoing chemotherapy. CLINICAL RELEVANCE: The findings may be useful
      for guiding intervention development for early detection and management of
      symptom interference with daily living, and place greater focus on patient self
      care to promote food choice and nutrition maintenance, especially in older
      patients and those whose caregivers are not their spouses.

PMID- 29569335
TI  - The taphonomic fate of isorenieratene in Lower Jurassic shales-controlled by
      iron?
AB  - Fossil derivatives of isorenieratene, an accessory pigment in brown-colored green
      sulfur bacteria, are often used as tracers for photic zone anoxia through Earth's
      history, but their diagenetic behavior is still incompletely understood. Here, we
      assess the preservation of isorenieratene derivatives in organic-rich shales (1.5
      8.4 wt.% TOC) from two Lower Jurassic anoxic systems (Bachental oil shale, Tyrol,
      Austria; Posidonia Shale, Baden-Wurttemberg, Germany). Bitumens and kerogens were
      investigated using catalytic hydropyrolysis (HyPy), closed-system hydrous
      pyrolysis (in gold capsules), gas chromatography-mass spectrometry (GC-MS) and
      gas chromatography combustion isotope ratio-mass spectrometry (GC-C-IRMS).
      Petrography and biomarkers indicate a syngenetic relationship between bitumens
      and kerogens. All bitumens contain abundant isorenieratane, diverse complex
      aromatized isorenieratene derivatives, and a pseudohomologous series of 2,3,6
      trimethyl aryl isoprenoids. In contrast, HyPy and mild closed-system hydrous
      pyrolysis of the kerogens yielded only minor amounts of these compounds. Given
      the overall low maturity of the organic matter (below oil window), it appears
      that isorenieratene and its abundant derivatives from the bitumen had not been
      incorporated into the kerogens. Accordingly, sulfur cross-linking, the key
      mechanism for sequestration of functionalized lipids into kerogens in anoxic
      systems, was not effective in the Jurassic environments studied. We explain this
      by (i) early cyclization/aromatization and (ii) hydrogenation reactions that have
      prevented effective sulfurization. In addition, (iii) sulfide was locally removed
      via anoxygenic photosynthesis and efficiently trapped by the reaction with
      sedimentary iron, as further indicated by elevated iron contents (4.0-8.7 wt.%)
      and the presence of abundant pyrite aggregates in the rock matrix. Although the
      combined processes have hampered the kerogen incorporation of isorenieratene and
      its derivatives, they may have promoted the long-term preservation of these
      biomarkers in the bitumen fraction via early defunctionalization. This particular
      taphonomy of aromatic carotenoids has to be considered in studies of anoxic iron
      rich environments (e.g., the Proterozoic ocean).

PMID- 29569336
TI  - Nonmedical prescription stimulant users experience subjective but not objective
      impairments in attention and impulsivity.
AB  - BACKGROUND AND OBJECTIVES: Nonmedical prescription stimulant use is frequently
      reported by college students to improve academic performance, yet it is unknown
      whether users truly experience cognitive impairments that may drive use. This
      research compared students with at least one report of nonmedical prescription
      stimulant use and nonusers on both self-report and objective measures of
      inattention and impulsivity. METHODS: Two studies examined inattention (N = 155)
      and impulsivity (N = 115) among college students. Participants completed self
      report questionnaires and cognitive tests, including Digit Span, the Paced
      Auditory Serial Addition Test, and a Continuous Performance Test to assess
      inattention, and the Balloon Analogue Risk Task and the Stop Signal Task to
      assess risk-taking and impulsivity. RESULTS: Self-reports of inattention and
      impulsive symptoms were significantly higher among users, controlling for gender,
      GPA, self-reported ADHD, alcohol use, and drug use; however, no objective
      differences were found. DISCUSSION AND CONCLUSIONS: Nonmedical prescription
      stimulant users may engage in use to overcome perceived deficits in cognitive
      abilities despite lack of objective evidence. SCIENTIFIC SIGNIFICANCE:
      Understanding discrepancies in objective performance and subjective reports may
      aid in the development of effective interventions for nonmedical prescription
      stimulant use. (Am J Addict 2018;27:238-244).

PMID- 29569338
TI  - Gorilla endoscopic sinus surgery: a life-saving collaboration between human and
      veterinary medicine.
AB  - BACKGROUND: Chronic rhinosinusitis is a common disease process in humans;
      however, in the primate population of gorillas, it has rarely been described.
      This case describes lifesaving sinus surgery on a critically ill gorilla
      performed by a human otolaryngology team in collaboration with the gorilla's
      veterinary medicine team. METHODS: The 35-year-old western silverback gorilla was
      treated for 3 months with aggressive medical therapy for a worsening sinus
      infection. When his condition became severe, a computed tomography (CT) scan was
      performed showing advanced chronic rhinosinusitis with nasal polyps vs other
      masses and some bone erosion. As his condition deteriorated further, a tertiary
      otolaryngology team performed sinus surgery using the latest technology
      available, including image guidance, steroid-eluting sinus stents, and balloon
      sinus dilation. The postoperative course was complicated by subcutaneous
      infection and eventual fistulization. Fortunately, with culture-directed
      antibiotic therapy his condition gradually improved. One year later he required
      revision sinus surgery. At that point allergy testing was performed followed by
      appropriate allergy medical therapy. Now, 3 years out from his initial surgery,
      he continues to do well and has fathered a young female gorilla. RESULTS: This
      case represents a unique collaboration between human physicians and
      veterinarians. The combined medical approach was critical to heal this ailing
      gorilla. This case discusses many of the challenges and offers recommendations
      for physicians who may be involved with similar care of animals in the future.
      CONCLUSION: The success of the surgical and medical treatment of this gorilla's
      life-threatening sinus infection required many experts, careful planning, and
      corporate generosity. The interaction between human and animal medicine would not
      have been successful without the close and trusting collaborations between human
      and veterinary health providers. We encourage human healthcare providers to seek
      volunteer opportunities through their local zoos by engaging in discussions with
      their local veterinarians.

PMID- 29569339
TI  - A D-vine copula-based model for repeated measurements extending linear mixed
      models with homogeneous correlation structure.
AB  - We propose a model for unbalanced longitudinal data, where the univariate margins
      can be selected arbitrarily and the dependence structure is described with the
      help of a D-vine copula. We show that our approach is an extremely flexible
      extension of the widely used linear mixed model if the correlation is homogeneous
      over the considered individuals. As an alternative to joint maximum-likelihood a
      sequential estimation approach for the D-vine copula is provided and validated in
      a simulation study. The model can handle missing values without being forced to
      discard data. Since conditional distributions are known analytically, we easily
      make predictions for future events. For model selection, we adjust the Bayesian
      information criterion to our situation. In an application to heart surgery data
      our model performs clearly better than competing linear mixed models.

PMID- 29569337
TI  - Diabetes, Cardiovascular Disorders and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Body
      Burden in Czech Patients 50 Years After the Intoxication.
AB  - The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication
      and the parameters of metabolic impairment was examined in the last eight male
      survivors of 80 workers exposed to TCDD during the production of herbicides in a
      chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390)
      pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) MUg. This puts
      these patients into the most severely intoxicated group of subjects, according to
      back-calculated levels of TCDD. The median TCDD blood level in eight controls was
      12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes,
      dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular
      reactivity, eye fundus hypertensive angiopathy and history of coronary heart
      disease - were assessed and compared to a general male population of comparable
      age. Measured parameters compared with a population of comparable age were as
      follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension
      (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary
      heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50%
      versus 14%). All eight patients (100% versus 43%) developed plaques in carotid
      arteries, six had stenosis >50% and two had a carotid intervention (stenting or
      endarterectomy). Total cholesterol levels decreased compared to the earlier study
      this patient group in 2008, most likely due to a more intensive use of lipid
      lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5
      fold) in the group of severely TCDD-intoxicated subjects than in a general
      population of comparable age. This suggests that TCDD plays a role in the
      development of metabolic impairment and vascular changes.

PMID- 29569340
TI  - Seventy Years of RN Effectiveness: A Database Development Project to Inform Best
      Practice.
AB  - BACKGROUND: The appropriate nursing staff mix is imperative to the provision of
      quality care. Nurse staffing levels and staff mix vary from country to country,
      as well as between care settings. Understanding how staffing skill mix impacts
      patient, organizational, and financial outcomes is critical in order to allow
      policymakers and clinicians to make evidence-informed staffing decisions. AIMS:
      This paper reports on the methodology for creation of an electronic database of
      studies exploring the effectiveness of Registered Nurses (RNs) on clinical and
      patient outcomes, organizational and nurse outcomes, and financial outcomes.
      METHODS: Comprehensive literature searches were conducted in four electronic
      databases. Inclusion criteria for the database included studies published from
      1946 to 2016, peer-reviewed international literature, and studies focused on RNs
      in all health-care disciplines, settings, and sectors. Masters-prepared nurse
      researchers conducted title and abstract screening and relevance review to
      determine eligibility of studies for the database. High-level analysis was
      conducted to determine key outcomes and the frequency at which they appeared
      within the database. RESULTS: Of the initial 90,352 records, a total of 626
      abstracts were included within the database. Studies were organized into three
      groups corresponding to clinical and patient outcomes, organizational and nurse
      related outcomes, and financial outcomes. Organizational and nurse-related
      outcomes represented the largest category in the database with 282 studies,
      followed by clinical and patient outcomes with 244 studies, and lastly financial
      outcomes, which included 124 studies. LINKING EVIDENCE TO ACTION: The
      comprehensive database of evidence for RN effectiveness is freely available at
      https://rnao.ca/bpg/initiatives/RNEffectiveness. The database will serve as a
      resource for the Registered Nurses' Association of Ontario, as well as a tool for
      researchers, clinicians, and policymakers for making evidence-informed staffing
      decisions.

PMID- 29569341
TI  - Bariatric surgery in solid organ transplant patients: Long-term follow-up results
      of outcome, safety, and effect on immunosuppression.
AB  - The surgical risk of transplanted patients is high, and the modified
      gastrointestinal anatomy after bariatric surgery (BS) may lead to pharmacokinetic
      alterations in the absorption of immunosuppressive drugs. Data on outcomes of BS
      and the safety and feasibility of maintaining immunosuppression and graft safety
      among solid organ transplanted patients are scarce. In the current study, weight
      loss, improvement in comorbidities, and changes in dosage and trough levels of
      immunosuppression drugs before and after BS were analyzed for all transplanted
      patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux
      en-Y gastric bypass (LRYGB) in our institution between November 2011 and January
      2017. Thirty-four patients (13 females, 21 males, average age 53 years) were
      included in the study. A successful weight loss (>50% excess weight loss in 28 of
      them [82%]) was recorded at the last follow-up. Comorbidities improved
      significantly. Immunosuppressive stability increased from 39% to 47% among all
      patients. The tacrolimus blood trough levels declined slightly, but remained
      within therapeutic range. These data suggest that LSG and LRYGB ensure good
      immunosuppressive maintenance together with significant weight loss and
      improvement in comorbidities without serious graft rejection or dysfunction. The
      surgical risk is higher than in the regular BS population.

PMID- 29569342
TI  - Structural characterization of POM6 Fab and mouse prion protein complex
      identifies key regions for prions conformational conversion.
AB  - : Conversion of the cellular prion protein PrPC into its pathogenic isoform PrPSc
      is the hallmark of prion diseases, fatal neurodegenerative diseases affecting
      many mammalian species including humans. Anti-prion monoclonal antibodies can
      arrest the progression of prion diseases by stabilizing the cellular form of the
      prion protein. Here, we present the crystal structure of the POM6 Fab fragment,
      in complex with the mouse prion protein (moPrP). The prion epitope of POM6 is in
      close proximity to the epitope recognized by the purportedly toxic antibody
      fragment, POM1 Fab also complexed with moPrP. The POM6 Fab recognizes a larger
      binding interface indicating a likely stronger binding compared to POM1. POM6 and
      POM1 exhibit distinct biological responses. Structural comparisons of the bound
      mouse prion proteins from the POM6 Fab:moPrP and POM1 Fab:moPrP complexes reveal
      several key regions of the prion protein that might be involved in initiating mis
      folding events. DATABASE: The structural data of moPrP:POM6 Fab complex are
      available in the PDB under the accession number
      www.rcsb.org/pdb/search/structidSearch.do?structureId=6AQ7.

PMID- 29569343
TI  - Relaxing liver ischemia reperfusion injury down 1 notch.

PMID- 29569344
TI  - Application of alginate microbeads as a carrier of bone morphogenetic protein-2
      for bone regeneration.
AB  - Bone morphogenetic protein-2 (BMP-2) is commonly used to enhance bone
      regeneration. The potential of BMP-2 for bone regeneration varies according to
      the concentration and release kinetics on the implanted site. Therefore, it is
      important to determine appropriate carriers of BMP-2. However, no optimal
      delivery vehicles have been identified. In the present study, we used alginate
      microbeads as a delivery vehicle for BMP-2. Alginate microbeads can be implanted
      onto the disease site through surgery or injection. The objective of this study
      was to evaluate that the osteoinductive properties of BMP-2 are effective in
      alginate microbeads as a carrier. In this study, the release kinetics of BMP-2 in
      alginate microbeads was evaluated using an enzyme-linked immunosorbent assay. BMP
      2 released from alginate microbeads induced high alkaline phosphatase activity in
      canine adipose tissue-derived mesenchymal stem cells. Injection of alginate
      microbeads with BMP-2 into mouse subcutaneous tissue, as well as surgical
      implantation into the 5-mm circular calvarial defects in rats, was conducted and
      the results showed extensive new bone formation. In conclusion, alginate
      microbeads can be utilized as an effective BMP-2 delivery vehicle for use in
      orthopedic surgery and as an injectable vehicle for a minimally invasive therapy.
      (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29569345
TI  - Fish oil treatment reduces chronic alcohol exposure induced synaptic changes.
AB  - Alcohol addiction is a chronic neuropsychiatric disorder that represents one of
      the most serious global public health problems. Yet, currently there still lacks
      an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs)
      have exhibited beneficial effects in a variety of neurological disorders,
      particularly in reversing behavioral deficits and neurotoxicity induced by
      prenatal alcohol exposure and binge drinking. In the present study, we
      investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on
      preventing relapse and alleviating withdrawal symptoms after chronic alcohol
      exposure. Our results demonstrated that fish oil significantly reduced the
      chronic alcohol exposure-induced aberrant dendritic morphologic changes of the
      medium-sized spiny neurons in the core and the shell of nucleus accumbens. This
      inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the
      post synaptic membranes of medium-sized spiny neurons and eventually alleviated
      withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3
      PUFAs are promising for treating withdrawal symptoms and alcohol dependence.

PMID- 29569347
TI  - First year medical student peer nominations of professionalism: A methodological
      detective story about making sense of non-sense.
AB  - This article explores the assessment of professionalism within a cohort of
      medical students during a sequential 13-week medical school histology and anatomy
      course. Across seven data points, students were asked to identify a
      professionalism role model from amongst their peers and to score Likert
      structured rationales for their decision. Based on density scores, an initial
      social network analysis identified six peer-nomination "stars." However, analysis
      of these stars revealed considerable variability and random-like "noise" in both
      the nomination and explanation data sets. Subsequent analyses of both data sets
      explored the possibility of underlying patterns in this noise using tests of
      reliability, principal components factor analysis, and fixed-effects regression
      analysis. These explorations revealed the presence of two dimensions
      (professional vs. supportive) in how students sought to explain their nomination
      decisions. Although data variability remained quite high, significantly less
      variability was present in the professional than in the supportive dimension,
      suggesting that academic helpfulness rationales are both empirically distinct and
      more mutable than rationales grounded in professionalism-related factors. In
      addition, data showed that the greater the stability in one's choice of a
      professionalism role model nomination over the T1-T7 data periods, the more
      stable one's reasons for that nomination-both for professionalism and supportive
      dimensions. Results indicate that while peer assessment of professionalism by
      first-year medical students may not be very reliable, students can differentiate
      between more personal and professional factors, even at this early stage in their
      professional development. Formal instruction within the pre-clinical curriculum
      should recognize and address this distinction. Anat Sci Educ. (c) 2018 American
      Association of Anatomists.

PMID- 29569346
TI  - Evolution of caudal fin ray development and caudal fin hypural diastema complex
      in spotted gar, teleosts, and other neopterygian fishes.
AB  - BACKGROUND: The caudal fin of actinopterygians transitioned from a heterocercal
      dorsoventrally asymmetrical fin to a homocercal externally symmetrical fin in
      teleosts through poorly understood evolutionary developmental mechanisms. We
      studied the caudal skeleton of major living actinopterygian lineages, including
      polypteriformes, acipenseriformes, Holostei (gars and bowfin), and teleosts,
      compared with reports of extinct neopterygians and basal teleosteans. We focused
      on the hypural diastema complex, which includes (1) a gap between hypurals 2 and
      3, that (2) separates two plates of connective tissue at (3) the branching of
      caudal vasculature; these features had been considered as a shared, derived trait
      of teleosts, a synapomorphy. RESULTS: These studies revealed that gars and
      teleosts share all three features of the hypural diastema complex. Absence of a
      complex with these features from bowfin, fossil Holostei, and stem Teleostei
      argues in favor of repetitive, independent emergence in several neopterygian and
      basal Teleostei lineages, or less likely, many independent losses. We further
      observed that, in gars and teleosts, the earliest developing lepidotrichia align
      with the horizontal adult body axis, thus participating in external symmetry.
      CONCLUSIONS: These results suggest that the hypural diastema complex in teleosts
      and gars represents a homoplasy among neopterygians and that it emerged
      repeatedly by parallel evolution due to shared inherited underlying genetic and
      developmental programs (latent homology). Because the hypural diastema complex
      exists in gars with heterocercal tails, this complex is independent of
      homocercality. Developmental Dynamics 247:832-853, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29569348
TI  - Investigation of phenylbutazone and its metabolite oxyphenbutazone in horse meat
      products during years 2013-2017.
AB  - This study showed the results of a monitoring program aimed at detecting the
      fraudulent use of horse meat in samples collected in the framework of official
      controls during the years 2013-2017 after the so-called horse meat scandal that
      caused a decreasing consumer confidence in the food industry, particularly in
      meat products. A total of 125 samples diversely distributed in the 5 years of
      monitoring were analyzed by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). The method was validated according to Commission Decision 657/2002/EC
      with regard to the following parameters: linearity, specificity, decision limit
      (CCalpha), detection capability (CCbeta), recovery, and precision (repeatability
      and within-laboratory reproducibility). Even if the results of this study
      revealed no positive sample, the need for constant assurance of food safety and
      consumers' health protection requires the implementation of preventive as well as
      corrective actions in the management of risks linked to the food chain in a more
      global context.

PMID- 29569349
TI  - Metal-Free Allylic Oxidation of Steroids Using TBAI/TBHP Organocatalytic
      Protocol.
AB  - A mild, efficient and organocatalytic allylic oxidation of steroids using a
      TBAI/TBHP protocol has been developed. A range of bioactive Delta5 -en-7-ones can
      be easily prepared from the corresponding Delta5 -steroids. The methodology
      features several advantages, including readily available starting materials,
      environmentally benign oxidant, high functional group compatibility, and metal
      free catalysis.

PMID- 29569350
TI  - Waist-to-height ratio remains an accurate and practical way of identifying
      cardiometabolic risks in children and adolescents.
AB  - AIM: We evaluated how effectively the waist-to-height ratio (WHtR) identified
      cardiometabolic risk (CMR) in children and adolescents, compared with the tri
      ponderal mass index, percentage of body fat and other obesity indexes. METHODS:
      Eligible subjects were recruited from three metropolitan regions of China from
      May 2013 to June 2014. Subjects with at least three of the following
      abnormalities - hypertension, dyslipidemia, elevated fasting blood glucose and
      central obesity - were defined as CMR1 and children with at least two were
      defined as CMR2. The area under the curve (AUC) of the receiver operating
      characteristic curve was used to compare how effectively obesity indexes
      predicted CMR. RESULTS: We recruited 3556 subjects aged 7-18 years. All five
      obesity indexes showed good, comparable performances in identifying CMR and the
      AUCs ranged from 0.89 to 0.90 for CMR1 and 0.83 to 0.85 for CMR2. The cut-off of
      0.467 for WHtR achieved a sensitivity of 0.91 and specificity of 0.80 for
      predicting CMR1, with the best cut-offs being 0.463 for boys and 0.469 for girls.
      CONCLUSION: The WHtR was a superior and practical screening tool for detecting
      CMR in this paediatric population, as it provided comparable accuracy to other
      methods and just required a simple calculation.

PMID- 29569351
TI  - Preliminary Clinical Evaluation of Acupuncture Therapy in Patients With
      Postpartum Sciatica.
AB  - INTRODUCTION: This study evaluated clinical outcomes following acupuncture
      treatment of postpartum sciatica. METHODS: One hundred eleven women with
      postpartum sciatica were enrolled in an acupuncture group (n = 86) or a control
      group (n = 25), according to their preference. Participants in the acupuncture
      group attended acupuncture therapy sessions 3 times a week for 4 weeks, while
      participants in the control group were assigned to bed rest. Outcome measures
      included the Roland Disability Questionnaire for sciatica, a visual analog scale
      for leg pain, and patient-reported perceived recovery. In addition, participants
      were surveyed after treatment to assess the acceptability of acupuncture therapy.
      RESULTS: The outcome scores for disability and leg pain were significantly lower
      in the acupuncture group compared with the control group (P < .05). All 86 women
      in the treatment group stated that acupuncture improved their well-being after
      treatment. At one month after treatment, 98% of participants in the treatment
      group reported recovery compared with 24% of the control group participants (P <
      .001). After treatment, 95% of lactating women in the acupuncture group believed
      that acupuncture had no significant interference with breast milk production. No
      adverse effects of acupuncture were reported. All participants in the acupuncture
      group stated they would choose acupuncture in case of relapse. However, the
      recurrence rate of sciatica in the acupuncture group (32%) was comparable to that
      of the control group (35%) at the one-year follow-up interview. DISCUSSION:
      Compared with bed rest, acupuncture might be an effective and acceptable strategy
      to relieve symptoms of postpartum sciatica.

PMID- 29569352
TI  - Have we done enough for people with fetal alcohol spectrum disorders?

PMID- 29569353
TI  - Cardioversion of persistent atrial fibrillation is associated with a 24-hour
      relapse gap: Observations from prolonged postcardioversion rhythm monitoring.
AB  - BACKGROUND: Many recurrences occur after electrical cardioversion (ECV) of atrial
      fibrillation (AF). Assessment of extent of remodeling and continuous prolonged
      rhythm monitoring might reveal actionable recurrence mechanisms. HYPOTHESIS:
      After ECV of AF specific patterns of arrhythmia recurrence can be distinguished.
      METHODS: All patients who underwent successful ECV due to persistent AF were
      included. Tissue velocity echocardiography during AF was performed before ECV to
      study atrial fibrillatory cycle length and fibrillatory velocity. After ECV, the
      heart rhythm of all patients was monitored 3 times daily during 4 weeks, and
      timing of recurrence was noted. RESULTS: In total, 50 patients (68% male) were
      included; mean age was 68 +/- 9 years. Median duration of the current AF episode
      was 102 (range, 74-152) days. Twenty-one (42%) patients showed recurrence of
      persistent AF. No recurrences occurred during the first 24 hours. There were no
      differences in clinical characteristics between patients with or without
      recurrence of AF. However, patients with early recurrence of AF had significantly
      higher precardioversion wall-motion velocity compared with patients who remained
      in sinus rhythm (2.8 [1.6-3.6] vs 1.4 [0.9-3.3] cm/s; P = 0.017), whereas atrial
      fibrillatory cycle length did not differ. CONCLUSIONS: In this study on 50
      patients successfully cardioverted for persistent AF, there was a relapse gap of
      >=24 hours. This phenomenon has not been well appreciated before and offers an AF
      free window of opportunity for electrocardiographically triggered cardiac imaging
      or complex electrophysiological procedures. Echocardiographic tissue velocity
      imaging may visualize atrial remodeling relevant to AF recurrence.

PMID- 29569354
TI  - Virologic failure and mortality in older ART initiators in a multisite Latin
      American and Caribbean Cohort.
AB  - INTRODUCTION: The "greying" of the HIV epidemic necessitates a better
      understanding of the healthcare needs of older HIV-positive adults. As these
      individuals age, it is unclear whether comorbidities and their associated
      therapies or the ageing process itself alter the response to antiretroviral
      therapy (ART). In this study, HIV treatment outcomes and corresponding risk
      factors were compared between older ART initiators and those who were younger
      using data from the Caribbean, Central and South America Network for HIV
      Epidemiology (CCASAnet). METHODS: HIV-positive adults (>=18 years) initiating ART
      at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were
      included. Patients were classified as older (>=50 years) or younger (<50 years)
      based on age at ART initiation. ART effectiveness was measured using three
      outcomes: death, virologic failure and ART treatment modification. Cox regression
      models for each outcome compared risk between older and younger patients,
      adjusting for other covariates. RESULTS: Among 26,311 patients initiating ART
      between 1996 and 2016, 3389 (13%) were >=50 years. The majority of patients in
      both >=50 and <50 age groups received a non-nucleoside reverse transcriptase
      inhibitor-based regimen (89% vs. 87%), did not have AIDS at baseline (63% vs.
      62%), and were male (59% vs. 58%). Older patients had a higher risk of death
      (adjusted hazard ratio (aHR) 1.64; 95% confidence intervals (CI): 1.48 to 1.83)
      and a lower risk of virologic failure (aHR: 0.73; 95% CI: 0.63 to 0.84). There
      was no difference in risk of ART modification (aHR: 1.00; 95% CI: 0.94 to 1.06).
      Risk factors for death, virologic failure and treatment modification were similar
      for each group. CONCLUSIONS: Older age at ART initiation was associated with
      increased mortality and decreased risk of virologic failure in our cohort of more
      than 26,000 ART initiators in Latin America and the Caribbean. To the best of our
      knowledge this is the first study from the region to evaluate ART outcomes in
      this growing and important population. Given the complexity of issues related to
      ageing with HIV, a greater understanding is needed in order to properly respond
      to this shifting epidemic.

PMID- 29569355
TI  - Vitamin D status, enterovirus infection, and type 1 diabetes in Italian
      children/adolescents.
AB  - At the time of the clinical onset of type 1 diabetes (T1D), we investigated 82
      pediatric cases in parallel with 117 non-diabetic controls matched by age,
      geographic area, and time of collection. The occurrence of an enteroviral
      infection was evaluated in peripheral blood using a sensitive method capable of
      detecting virtually all human enterovirus (EV) types. While non-diabetic controls
      were consistently EV-negative, 65% of T1D cases carried EVs in blood. The vitamin
      D status was assessed by measuring the concentration of 25-hydroxyvitamin D
      [25(OH)D] in serum. Levels of 25(OH)D were interpreted as deficiency (<=50
      nmol/L), insufficiency (52.5-72.5 nmol/L), and sufficiency (75-250 nmol/L). In
      T1D cases, the median serum concentration of 25(OH)D was 54.4 +/- 27.3 nmol/L vs
      74.1 +/- 28.5 nmol/L in controls (P = .0001). Diabetic children/adolescents
      showed deficient levels of vitamin D 25(OH)D (ie, 72.5 nmol/L) in 48.8% cases vs
      17.9% in non-diabetic controls (P = .0001). Unexpectedly, the median vitamin D
      concentration was significantly reduced in virus-positive vs virus-negative
      diabetics (48.2 +/- 22.5 vs 61.8 +/- 31.2 nmol/L; P = .015), with deficient
      levels in 58.5% vs 31.0%, respectively. Thus, at the time of clinical onset, EV
      positive cases had reduced vitamin D levels compared with EV-negative cases. This
      could indicate either that the virus-negative children/adolescents had been hit
      by a non-infectious T1D-triggering event, or that children/adolescents with
      proper levels of vitamin D had been able to rapidly clear the virus. Thus, it
      would be important to assess whether adequate vitamin D supplementation before or
      during the prediabetic phase of T1D may counteract the diabetogenic potential of
      infectious pathogens.

PMID- 29569356
TI  - Metallothermic Reduction of Silica Nanoparticles to Porous Silicon for Drug
      Delivery Using New and Existing Reductants.
AB  - In this study, the influence of metals (Mg, Al, and Ca) and reaction conditions
      (time, temperature, and metal grain size) on the metallothermic reduction of
      Stober silica nanoparticles (NPs) to form porous Si has been explored. Mg metal
      was found to be an effective reducing agent even at temperatures below its
      melting point; however, it also induced a high degree of structural damage and
      morphology change. Al was effective in reducing silica NPs only at its melting
      point or above, but the resulting particles retained a higher degree of
      structural morphology as compared to those reduced using Mg. Ca was found to be
      ineffective in reducing silica. A new reductant, a mixture of 70 % Mg and 30 %
      Al, was found to induce the least amount of morphology change, and the reactions
      proceeded at a temperature (450  degrees C) lower than those required with Mg or
      Al individually. Furthermore, porous Si NPs obtained using Mg, Al, and the
      mixture of 70 % Mg and 30 % Al as reductants have been investigated as carriers
      for ibuprofen loading and release. Porous Si obtained from reductions with Mg and
      the Mg/Al mixture showed higher drug loading and a sustained drug release
      profile, whereas porous Si obtained from Al reduction had lower loading and
      showed a conventional release profile over 24 h.

PMID- 29569357
TI  - Postpartum Depressive Symptoms: Gestational Weight Gain as a Risk Factor for
      Adolescents Who Are Overweight or Obese.
AB  - INTRODUCTION: Obesity is a risk factor for adverse physical health outcomes
      during pregnancy. Much less is known about the association between obesity and
      maternal mental health. Evidence suggests that prenatal depression is associated
      with excessive weight gain during pregnancy and that this relationship may vary
      according to pregravid body mass index (BMI). Young women may be particularly
      vulnerable to postpartum depression. The objective of this study is to examine
      the association between prepregnancy BMI, gestational weight gain, and postpartum
      depressive symptoms among adolescents. METHODS: Participants were 505 pregnant
      adolescents aged 14 to 21 years followed during pregnancy and 6 months
      postpartum. Data were collected via interviews and medical record abstraction.
      Multilevel linear mixed models were used to test the association between
      excessive gestational weight gain as defined by National Academy of Medicine
      Guidelines and postpartum depressive symptoms measured via the validated Center
      for Epidemiologic Studies Depression (CES-D) scale. Analyses controlled for
      sociodemographic factors (maternal age, race, ethnicity, relationship status),
      health behaviors (nutrition, physical activity), prenatal depressive symptoms,
      and postpartum weight retention. RESULTS: Prepregnancy BMI was classified as
      follows: 11% underweight, 53% healthy weight, 19% overweight, and 18% obese. One
      half (50%) of participants exceeded recommended guidelines for gestational weight
      gain. Adolescents with excessive gestational weight gain who entered pregnancy
      overweight or obese had significantly higher postpartum depressive symptoms
      (beta, 2.41; SE, 1.06 vs beta, 2.58; SE, 1.08, respectively; both P < .05)
      compared with those with healthy prepregnancy BMI and appropriate gestational
      weight gain. Adolescents who gained gestational weight within clinically
      recommended guidelines were not at risk for increased depressive symptoms.
      DISCUSSION: Adolescents who enter pregnancy overweight or obese and experience
      excessive weight gain may be at increased risk for postpartum depressive
      symptoms. Health care providers should offer preventive interventions during
      pregnancy and the interconceptional period to support healthy weight gain and
      safeguard women's mental health.

PMID- 29569358
TI  - Prefrontal cortex NG2 glia undergo a developmental switch in their responsiveness
      to exercise.
AB  - Aerobic exercise is known to influence brain function, e.g., enhancing executive
      function in both children and adults, with many of these influences being
      attributed to alterations in neurogenesis and neuronal function. Yet
      oligodendroglia in adult brains have also been reported to be highly responsive
      to exercise, including in the prefrontal cortex (PFC), a late myelinating region
      implicated in working memory. However, whether exercise affects oligodendroglia
      or myelination in juveniles, either in the PFC or in other brain regions, remains
      unknown. To address this, both juvenile and young adult mice were provided free
      access to running wheels for four weeks followed by an analysis of
      oligodendrocyte development and myelination in the PFC and the corpus callosum, a
      major white matter tract. Working memory and PFC NG2+ cell development were both
      affected by exercise in juvenile mice, yet surprisingly these exercise-mediated
      effects were distinct in juveniles and young adults. In the PFC, NG2+ cell
      proliferation was increased in exercising juveniles, but not young adults,
      whereas newly-born oligodendrocyte production was increased in exercising young
      adults, but not juveniles. Although no overall changes in myelin genes were
      found, elevated levels of Monocarboxylate Transporter 1, a glial lactate
      transporter important during active myelination, were found in the PFC of
      exercising young adults. Overall our findings reveal that long-term exercise
      modulates PFC glial development and does so differentially in juvenile and young
      adult mice, providing insight into the cellular responses that may underlie
      cognitive benefits to teenagers and young adults in response to exercise. (c)
      2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 687-700, 2018.

PMID- 29569359
TI  - Surface modification of polypropylene for enhanced layer-by-layer deposition of
      polyelectrolytes.
AB  - We have performed three distinct plasma enhanced chemical vapor deposition
      procedures that can be widely and consistently used in commercially available
      plasma systems to modify the surface of hydrocarbon-based biomaterials such as
      polypropylene. In particular, we have evaluated the feasibility of these
      procedures to provide consistent and stable charged substrates to perform layer
      by-layer (LbL) coatings. Surface characterization of both plasma and LbL coatings
      were done using X-ray photoelectron spectroscopy, attenuated total reflection
      Fourier transform infrared spectroscopy, contact angle measurements and surface
      staining. Results showed successful surface grafting of functional groups in all
      plasma procedures that led to increased hydrophilicity and uniform LbL coatings
      with different efficiencies. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 2078-2085, 2018.

PMID- 29569360
TI  - The risk of hypertension and cardiovascular disease in women with uterine
      fibroids.
AB  - Women with fibroids have a notably high hypertension risk. However, adjusted data
      regarding other cardiovascular disease (CVD) risk factors are scarce. In this
      cross-sectional study, CVD risk factors, hemodynamic parameters, and asymptomatic
      organ damage were analyzed between women with uterine fibroids and controls in a
      multi-ethnic population. In total, 104 women with self-reported fibroids and 624
      controls were included. Women with fibroids had significantly higher odds to have
      hypertension (OR 3.4; 95% CI 2.2-5.2), diabetes (1.7; 1.0-2.9), and
      hypercholesterolemia (1.8; 1.1-3.2). After adjustment for confounders, only the
      odds ratio for hypertension was significant (1.8; 1.1-3.1). Asymptomatic organ
      damage occurred significantly more often in women with fibroids (66.7%; 95% CI
      55.8%-77.6% vs 42.9%; 38.0-47.8 in controls), especially in the younger age group
      (respectively 48.5%; 31.1%-65.9% vs 22.1%; 17.0-27.2). In this study, women with
      fibroids had a remarkably high hypertension risk compared to controls, with more
      asymptomatic organ damage, in particular young women.

PMID- 29569361
TI  - Commentary: Providing technical assistance for the state targeted response for
      opioid use disorders: Time is of the essence.

PMID- 29569363
TI  - A Meta-Synthesis of the Birth Experiences of African Immigrant Women Affected by
      Female Genital Cutting.
AB  - INTRODUCTION: The purpose of this qualitative meta-synthesis was to understand
      the labor and birth experiences of immigrant women in countries of resettlement
      who have a history of female genital cutting (FGC), also known as female genital
      mutilation or female circumcision. METHODS: We used a meta-ethnography approach
      to synthesize the literature on this topic. We searched PubMed, Embase, Web of
      Science, CINAHL, PsycINFO, and Sociological Abstracts databases from inception to
      May 2016 using the search terms female genital cutting, female circumcision,
      clitorectomy, clitoridectomy, pharaonic circumcision, genital circumcision,
      female genital mutilation, infibulation, and deinfibulation. Our inclusion
      criteria were 1) peer-reviewed, original qualitative research; 2) focused on
      populations affected by FGC or their health care providers; 3) conducted in a
      country where FGC is not documented as an indigenous practice; 4) English
      language; and 5) included a description of postmigratory labor and birth
      experiences of women affected by FGC. Fourteen articles were included. RESULTS:
      Two new syntheses emerged from our sample of studies including African immigrant
      women primarily resettled in Europe and the United States. First, birth after FGC
      in the context of resettlement included pain and anxiety, and has the potential
      to retraumatize. Second, while women experienced nostalgia for familiar
      traditions and perceived disrespect in their new setting, they questioned
      traditions, including the role of FGC, in their and their daughters' lives.
      DISCUSSION: The negative birth experiences of women affected by FGC highlight the
      need to improve care for this population. Health care professionals can serve as
      a source of support for women affected by FGC by acknowledging and addressing FGC
      in their care and actively listening to their perspectives and concerns.

PMID- 29569362
TI  - Temporally restricted death and the role of p75NTR as a survival receptor in the
      developing sensory nervous system.
AB  - The peripheral somatosensory system overproduces neurons early in development
      followed by a period of cell death during final target innervation. The decision
      to survive or die in somatosensory neurons of the dorsal root ganglion (DRG) is
      mediated by target-derived neurotrophic factors and their cognate receptors.
      Subsets of peripheral somatosensory neurons can be crudely defined by the
      neurotrophic receptors that they express: peptidergic nociceptors (TrkA+),
      nonpeptidergic nociceptors (Ret+), mechanoreceptors (Ret+ or TrkB+), and
      proprioceptors (TrkC+). A direct comparison of early developmental timing between
      these subsets has not been performed. Here we characterized the accumulation and
      death of TrkA, B, C, and Ret+ neurons in the DRG as a function of developmental
      time. We find that TrkB, TrkC, and Ret-expressing neurons in the DRG complete
      developmental cell death prior to TrkA-expressing neurons. Given the broadly
      defined roles of the neurotrophin receptor p75NTR in augmenting neurotrophic
      signaling in sensory neurons, we investigated its role in supporting the survival
      of these distinct subpopulations. We find that TrkA+, TrkB+, and TrkC+ sensory
      neuron subpopulations require p75NTR for survival, but proliferating progenitors
      do not. These data demonstrate how diverging sensory neurons undergo successive
      waves of cell death and how p75NTR represses the magnitude, but not developmental
      window of this culling. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol 78:
      701-717, 2018.

PMID- 29569364
TI  - Ambulatory blood pressure in relation to oxygen desaturation index as
      simultaneously assessed by nighttime finger pulse oximetry at home.
AB  - We investigated the relationship between ambulatory blood pressure (BP) and
      oxygen desaturation index (ODI), while accounting for pulse rate and age. ODI was
      assessed by overnight finger pulse oximetry in 2342 participants on the day of
      ambulatory BP monitoring, and calculated as the number of desaturation episodes
      per sleeping hour. Both BP and pulse rate increased significantly (P <= .006)
      from normal (< 5 events/h) to mildly (5-14), moderately (15-30), and severely (>=
      30 events/h) elevated ODI. The association for BP was substantially attenuated by
      accounting for pulse rate (partial r2 from .003-.012 to .002-.006). In adjusted
      analysis, the associations of 24-hour diastolic BP and 24-hour pulse rate with
      ODI were dependent on age (P <= .0001) and only significant in younger subjects
      (< 60 years, P <= .0001). In conclusion, the association between ambulatory BP
      and ODI was partially mediated by pulse rate, a measure of sympathetic activity,
      and was more prominent in younger subjects.

PMID- 29569365
TI  - Structural effects of point mutations in proteins.
AB  - A structural database of 11 families of chains differing by a single amino acid
      substitution has been built. Another structural dataset of 5 families with
      identical sequences has been used for comparison. The RMSD computed after a
      global superimposition of the mutated protein on each native one is smaller than
      the RMSD calculated among proteins of identical sequences. The effect of the
      perturbation is very local, and not necessarily the highest at the position of
      the mutation. A RMSD between mutated and native proteins is computed over a 3
      residue or a 7-residue window at each position. To separate the effects of
      structural fluctuations due to point mutations from other sources, pair RMSD have
      been translated into P values which themselves are included in a score called P
      RANK. This score allows highlighting small backbone distortions by comparing
      these RMSD between mutated and native positions to the RMSD at the same positions
      in the absence of a mutation. It results from the P-RANK that 38% of all
      mutations produce a significant effect on the displacement. When compared with a
      random distribution of RMSD at un-mutated positions, we show that, even if the
      RMSD is greater when the mutation is in loops than in regular secondary
      structure, the relative effect is more important for regular secondary structures
      and for buried positions. We confirm the absence of correlation between RMSD and
      the predicted variation of free energy of folding but we found a small
      correlation between high RMSD and the error in the prediction of DeltaDeltaG.

PMID- 29569366
TI  - Assessment of recording bias in pregnancy studies using health care databases: An
      application to neurologic conditions.
AB  - BACKGROUND: Pre-existing conditions are imperfectly recorded in health care
      databases. We assessed whether pre-existing neurologic conditions (epilepsy,
      multiple sclerosis [MS]) were differentially recorded in the presence of major
      obstetric outcomes (Caesarean delivery, preterm delivery, preeclampsia) in
      delivery records. We also evaluated the impact of differential recording on
      measures of frequency and association between the conditions and outcomes.
      METHODS: The 2011-2014 Truven Health MarketScan(r) Commercial Claims Dataset was
      used to identify pregnancies. We calculated the relative recording of epilepsy
      and MS at delivery hospitalization compared with a 270-day pre-delivery window
      both overall and by the presence of major obstetric outcomes. We estimated risk
      ratios for the association between epilepsy and MS with the outcomes for each
      ascertainment window. RESULTS: We identified 909 065 pregnancies in women
      continuously enrolled from 270-days before the delivery date. Of women with
      epilepsy identified in the pre-delivery window, 73% had the condition coded at
      delivery. For MS, the proportion was 60%. MS recording at delivery did not vary
      by obstetric outcomes, however, delivery-coded epilepsy was less likely confirmed
      in the pre-delivery window in the presence of preeclampsia. Generally, the period
      of ascertainment did not meaningfully impact risk ratios, however, the risk ratio
      for preeclampsia associated with epilepsy was 1.67 (95% CI 1.47, 1.90) when
      epilepsy was ascertained at delivery and 1.26 (95% CI 1.07, 1.48) when epilepsy
      was ascertained in the pre-delivery window (heterogeneity, P = .007).
      CONCLUSIONS: Ascertainment of epilepsy and MS in delivery hospitalization records
      underestimated prevalence. However, the window of recording generally did not
      impact risk ratio estimates of associations with obstetric outcomes.

PMID- 29569367
TI  - Carbon Quantum Dot Implanted Graphite Carbon Nitride Nanotubes: Excellent Charge
      Separation and Enhanced Photocatalytic Hydrogen Evolution.
AB  - Graphite carbon nitride (g-C3 N4 ) is a promising candidate for photocatalytic
      hydrogen production, but only shows moderate activity owing to sluggish
      photocarrier transfer and insufficient light absorption. Herein, carbon quantum
      dots (CQDs) implanted in the surface plane of g-C3 N4 nanotubes were synthesized
      by thermal polymerization of freeze-dried urea and CQDs precursor. The CQD
      implanted g-C3 N4 nanotubes (CCTs) could simultaneously facilitate photoelectron
      transport and suppress charge recombination through their specially coupled
      heterogeneous interface. The electronic structure and morphology were optimized
      in the CCTs, contributing to greater visible light absorption and a weakened
      barrier of the photocarrier transfer. As a result, the CCTs exhibited efficient
      photocatalytic performance under light irradiation with a high H2 production rate
      of 3538.3 MUmol g-1  h-1 and a notable quantum yield of 10.94 % at 420 nm.

PMID- 29569368
TI  - Optimal reconstruction of left ventricular outflow tract obstruction before
      surgical myectomy in a case with hypertrophic obstructive cardiomyopathy.
AB  - We present optimally reconstructed three-dimensional computed tomography images
      of left ventricular outflow obstruction, comprehensive left ventriculography, and
      comparable intraoperative transesophageal echocardiography, as well as serial
      operative pictures, to facilitate the understanding of live-heart anatomy of
      hypertrophic obstructive cardiomyopathy. As shown in this case, detailed
      morphological analysis around the left ventricular outflow tract using
      preoperative computed tomography would be feasible and useful. The present case
      highlights the importance of obtaining complete three-dimensional information
      present in the acquired computed tomography dataset because computed tomography
      is not entirely noninvasive or free of radiation exposure and contrast material.

PMID- 29569369
TI  - Terpenes from Euphorbia antiquorum and Their in Vitro Anti-HIV Activity.
AB  - Three new compounds (1 - 3), including two euphane type triterpenes, 24,24
      dimethoxy-25,26,27-trinoreuphan-3beta-ol (1) and (24S)-24-hydroperoxyeupha-8,25
      dien-3beta-ol (2), and an ent-atisine diterpene, ent-atisane-3alpha,16alpha,17
      triol (3), were isolated from an acetone extract of the stems of Euphorbia
      antiquorum, together with eight known diterpenes (4 - 11). The structures of
      compounds (1 - 11) were elucidated using NMR and MS spectroscopic methods.
      Compound 7 showed moderate activity against HIV-1 replication in vitro (EC50 =
      1.38 MUm).

PMID- 29569370
TI  - Putting gross anatomy into the curriculum: New anatomy syllabi for nursing and
      pharmacy students.

PMID- 29569371
TI  - Molecular and functional characterization of three odorant binding proteins from
      the oriental fruit moth Grapholita molesta (Busck) (Lepidoptera: Tortricide).
AB  - Odorant binding proteins (OBPs) act in recognizing odor molecules and their most
      well-studied functions are transporting odors across the sensillum lymph to
      olfactory receptor neurons within the insect antennal sensillum. The adults of
      Grapholita molesta highly depend on olfactory cues in locating host plants and
      selecting oviposition sites, in which OBPs play an important role in perceiving
      and recognizing host plant volatiles. Exploring the physiological function of
      OBPs could facilitate our understanding of their importance in insects' chemical
      communication. In this study, three OBP genes were cloned and named GmolOBP4,
      GmolOBP5, and GmolOBP10. Quantitative real-time PCR results indicated that
      GmolOBP4 and GmolOBP10 were predominantly expressed in adult antennae and
      GmolOBP5 was expressed in multiple tissues, including head, legs, and wings in
      addition to antennae. The binding affinities of the three recombinant GmolOBPs
      (rGmolOBPs) with four sex pheromone components and twenty-nine host plant
      volatiles were measured using 1-N-Phenyl-naphthylamine as a fluorescence probe.
      The three rGmolOBPs exhibited specific binding properties to potential ligands,
      GmolOBP4 and GmolOBP10 bound to minor sex pheromone components, such as (Z)-8
      dodecenyl alcohol and dodecanol, respectively. rGmolOBP4 showed intermediate
      binding ability with hexanal, benzyl alcohol, and pear ester, rGmolOBP5 had a
      weak affinity for benzaldehyde, pear ester and, methyl jasmonate, and rGmolOBP10
      showed strong binding capacity toward hexanol, decanol, and alpha-ocimene. We
      speculate that the GmolOBP4 and GmolOBP10 have dual functions in perception and
      recognition of host plant volatiles and sex pheromone components, while GmolOBP5
      may serve other function(s).

PMID- 29569373
TI  - Isocapnic hyperventilation in anaesthesia practice. Clinical and experimental
      studies.

PMID- 29569372
TI  - Solid lipid nanoparticles carrying Eugenia caryophyllata essential oil: the novel
      nanoparticulate systems with broad-spectrum antimicrobial activity.
AB  - : In this study, solid lipid nanoparticles containing Eugenia caryophyllata
      essential oil (SLN-EO) were prepared by high-shear homogenization and ultrasound
      methods, and used to eradicate pathogens. SLN formulations were evaluated for
      their size, zeta potential and encapsulation efficacy (EE). The morphological and
      thermal properties of the formulations were analysed by transmission electron
      microscopy (TEM) and differential scanning calorimetry methods. The lead
      formulations were chosen and tested with minimum inhibitory concentration (MIC),
      MBC and time-kill methods to investigate the antimicrobial activity against
      Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus and Candida
      albicans. The particle size of three final formulations were 397 +/- 10.1, 786.9
      +/- 11 and 506.4 +/- 22 nm respectively. The zeta potential of all formulations
      was negative values. The size of the formulations was slightly increased during 3
      months storage at 25 degrees C. The TEM imaging showed that formulation had
      spherical shape. The EE of EO was estimated approximately 70%. MIC and MCC values
      of SLN-EO were lower than those of the oil alone. The time-kill studies showed
      that SLN-EO was either equivalent to or better than EO (P-value <0.05). The
      results of this study highlighted the effectiveness of SLN formulations against
      human pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial resistance to
      antibiotics is a major problem in the treatment of diseases. Therefore,
      overcoming antimicrobial resistance is an urgent need. Drug delivery via
      nanoparticles and applying natural products are promising approaches to reduce
      microbial resistance. This study is designed to evaluate the antimicrobial
      activity of solid lipid nanoparticles (SLN) containing Eugenia caryophyllata
      essential oil (EO) against human pathogens. The results indicated that the
      antimicrobial activity of EO was remarkably enhanced when encapsulated in SLN.

PMID- 29569374
TI  - Overexpression of WD repeat domain 5 associates with aggressive
      clinicopathological features and unfavorable prognosis in head neck squamous cell
      carcinoma.
AB  - BACKGROUND: WD repeat domain 5 (WDR5), a core member of Mixed lineage leukemia
      (MLL) and SET1 histone H3 lysine 4 (H3K4) methyltransferase complexes, is
      involved in multiple biological and pathological processes. Its deregulation in
      cancer and pro-tumorigenic roles has been increasingly appreciated. However, the
      expression pattern of WDR5 and its biological functions in head neck squamous
      cell carcinoma (HNSCC) have not been well established. METHODS: The expression of
      WDR5 mRNA in HNSCC was determined by data mining and interrogation using publicly
      available databases. Its protein expression was measured by immunohistochemistry
      in a retrospective cohort of primary HNSCC samples. Moreover, the associations
      between WDR5 expression and various clinicopathological parameters and patient
      survival were assessed. The pro-tumorigenic roles of WDR5 in HNSCC were further
      delineated in vitro by loss-of-function assay. RESULTS: Our bioinformatics
      analyses revealed that WDR5 mRNA was significantly overexpressed in 3 HNSCC
      cohorts. WDR5 protein was markedly upregulated in HNSCC samples as compared to
      normal counterparts and its overexpression significantly associated with large
      tumor size, advanced clinical stage (chi-square test, P = .048, .006) and reduced
      overall and disease-free survival (Kaplan-Mier analyses, Log-rank test, P =
      .0137, .0154). Univariate and multivariate survival analyses further revealed
      WDR5 protein abundance as an independent prognostic factor for patients' overall
      survival. Moreover, WDR5 knockdown significantly inhibited cell proliferation,
      migration and invasion, and induced cell apoptosis in HNSCC cells. CONCLUSIONS:
      Our findings reveal that WDR5 is aberrantly overexpressed in HNSCC and associates
      with aggressiveness and unfavorable prognosis, thus representing a novel
      diagnostic and prognostic biomarker for HNSCC.

PMID- 29569375
TI  - Roflumilast Usage from 2010 to 2016: A Danish Nationwide Drug Utilization Study.
AB  - Roflumilast, a phosphodiesterase-4-inhibitor, is marketed as add-on treatment to
      inhaled bronchodilators and corticosteroids in COPD patients with frequent
      exacerbations. Although marketed since 2010, usage pattern of roflumilast for an
      entire nation has not previously been explored. This study aimed to estimate the
      total utilization of roflumilast in Denmark during 2010 to 2016, using the Danish
      nationwide health registers. We identified 1573 individuals (47% males) who used
      roflumilast during the study period, of whom 705 (45%) redeemed only one
      prescription. Of all patients initiating roflumilast, 67% discontinued treatment
      within the first year. The rate of treatment initiation decreased 73% from 2011
      (7.5/100,000 person-years) to 2016 (2.0/100,000 person-years) concurrent with a
      stable prevalence of 3.0-4.0/100,000 persons throughout the study period. The
      median duration of roflumilast use was 76 days. Patients with severe comorbidity
      tended to exhibit a lower degree of early discontinuation (Charlson Comorbidity
      Index 3+: odds ratio [OR]: 0.59; 95% confidence interval [CI] 0.33-1.04), as well
      as patients with a COPD-related admission within a year prior to roflumilast
      initiation (OR 0.62; 95% CI 0.49-0.80). The decreasing incidence and high level
      of early roflumilast discontinuation could be due to lack of benefit, a low
      awareness of romiflulast's indication among physicians, secondary to a
      challenging prescribing procedure or to adverse effects.

PMID- 29569376
TI  - Contrasting features of childhood and adolescent melanomas.
AB  - BACKGROUND/OBJECTIVES: Melanoma in children and adolescents is uncommon, and
      there are limited data on pediatric outcomes. Several studies have shown
      comparable survival rates in children and adults, but other research demonstrates
      that prepubescent children have more favorable outcomes. This study aims to
      compare childhood and adolescent melanoma. METHODS: Retrospective cohort study of
      children who received a melanoma diagnosis at the Massachusetts General Hospital
      between January 1, 1995, and December 21, 2016. Childhood melanoma is defined as
      disease occurring in patients younger than 11 years old, and adolescent melanoma
      is defined as disease occurring in patients 11 to 19 years old. Patients
      diagnosed with ocular melanoma and borderline tumors of uncertain malignant
      potential were excluded. This analysis compares clinical, histopathologic, and
      outcome characteristics of childhood and adolescent melanoma. RESULTS: Thirty-two
      children with melanoma were identified (12 children, 20 adolescents). The
      spitzoid melanoma subtype was significantly more common in children (6/12) than
      adolescents (2/20) (P = .01). Four adolescents and no children with melanoma died
      from melanoma, and survival was significantly different between the age groups (P
      = .04). Median follow-up time for survivors was 3.6 years. CONCLUSIONS: These
      results suggest that children and adolescents present with different melanoma
      subtypes and that adolescents have a more aggressive disease course than
      children.

PMID- 29569378
TI  - Rates of myocardial infarction and stroke in patients initiating treatment with
      SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical
      practice: Results from the CVD-REAL study.
AB  - The multinational, observational CVD-REAL study recently showed that initiation
      of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with
      significantly lower rates of death and heart failure vs other glucose-lowering
      drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the
      association between initiation of SGLT-2i vs oGLDs and rates of myocardial
      infarction (MI) and stroke. Medical records, claims and national registers from
      the USA, Sweden, Norway and Denmark were used to identify patients with T2D who
      newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or
      empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within
      each country to predict initiation of SGLT-2i, and patients were matched 1:1 in
      the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using
      Cox regression models. Overall, 205 160 patients were included. In the intent-to
      treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and
      stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of
      SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI:
      HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P =
      .02). These findings complement the results of the cardiovascular outcomes
      trials, and offer additional reassurance with regard to the cardiovascular
      effects of SGLT-2i, specifically as it relates to ischaemic events.

PMID- 29569377
TI  - Immune regulation by microbiome metabolites.
AB  - Commensal microbes and the host immune system have been co-evolved for mutual
      regulation. Microbes regulate the host immune system, in part, by producing
      metabolites. A mounting body of evidence indicates that diverse microbial
      metabolites profoundly regulate the immune system via host receptors and other
      target molecules. Immune cells express metabolite-specific receptors such as P2X7
      , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X
      receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets.
      Microbial metabolites and their receptors form an extensive array of signals to
      respond to changes in nutrition, health and immunological status. As a
      consequence, microbial metabolite signals contribute to nutrient harvest from
      diet, and regulate host metabolism and the immune system. Importantly, microbial
      metabolites bidirectionally function to promote both tolerance and immunity to
      effectively fight infection without developing inflammatory diseases. In
      pathogenic conditions, adverse effects of microbial metabolites have been
      observed as well. Key immune-regulatory functions of the metabolites, generated
      from carbohydrates, proteins and bile acids, are reviewed in this article.

PMID- 29569379
TI  - Risk factors for blood stream infections in multiple myeloma: A population-based
      study of 1154 patients in Denmark.
AB  - OBJECTIVES: Multiple myeloma (MM) patients are at high risk of developing
      infections. The risk factors for blood stream infections (BSI) in MM patients
      are, however, less described. The aim of this study was to analyze the
      epidemiology of and risk factors for BSI in an unselected MM population. METHODS:
      Nationwide Danish MM data of 1154 patients diagnosed from 2010 to 2013 were
      linked with nationwide data on blood cultures (BCs; from 2010 to 2016) to assess
      the peak period of having a BC taken and BC positive for pathogenic
      microorganisms. RESULTS: The highest number of BC was taken in the period from
      day -30 to day +180 from date of MM diagnosis. Risk factors for having a BC
      sampling within the peak period were as follows: immunoparesis (HR 1.5 [1.1-2.1];
      P = .007), ISS-III (HR 1.3 [1.0-1.7]; P = .035), high creatinine (HR 1.4 (1.0
      2.0); P = .046), and high lactate dehydrogenase (LDH) (HR 2.8 (1.6-4.7; P <
      .001). Risk factors for positive BC during the peak period were ISS-III (HR 2.0
      (1.1-3.7); P = .023) and high LDH (HR 3.4 [1.1-10.3]; P = .028). CONCLUSIONS: Our
      results show that MM patients with aggressive disease presentation are at the
      highest risk of developing BSI. Furthermore, our study implies that MM is
      diagnosed in relation to a serious infection for a large number of patients.

PMID- 29569380
TI  - Modeling Missed Care: Implications for Evidence-Based Practice.
AB  - BACKGROUND: There is a growing nursing literature that views missed care as an
      inevitable consequence of work intensification associated with the rationing of
      nursing and material resources available to deliver care. Global studies
      recognize that missed care is now ubiquitous, although studies tend to be
      conducted in one region, rather than nationwide. This study seeks to understand
      the Australian context of missed care. AIMS: To explore self-reported reasons for
      missed care and to identify the main factors for predicting missed care within a
      sample of Australian nurses and midwives working in public and private hospitals
      in New South Wales, Victoria, Tasmania, and South Australia. METHODS: A
      nonexperimental, descriptive method using Kalisch's (2006) MISSCARE survey was
      used. Responses from 1,195 nursing and midwifery staff with differing
      qualifications, English language skills, and Australian employment settings were
      analyzed using Rasch analysis and then modeled using the Structural Equation
      Modeling. RESULTS: The frequency of missed care on the morning shift directly
      impacted on higher priority care missed during the afternoon shift. Staff skill
      mix imbalances and perceived inadequacy of staff numbers for the work demands
      further exacerbated all aspects of care during afternoon shifts. Other major
      factors associated with missed care were the different clinical work settings and
      staff to patient ratios. LINKING EVIDENCE TO ACTION: The incidences, types, and
      reasons behind missed care are a multidimensional construct which can be
      predicted when known significant factors behind missed care are simultaneously
      accounted for.

PMID- 29569381
TI  - An exploration of predictors of children's nurses' attitudes, knowledge,
      confidence and clinical behavioural intentions towards children and young people
      who self-harm.
AB  - AIMS AND OBJECTIVES: To explore the potential predictors of children's nurses'
      attitudes, knowledge and confidence towards caring for children and young people
      admitted to hospital with self-harm. BACKGROUND: Admissions to paediatric
      inpatient settings for individuals who have self-harmed are growing. Limited
      previous research suggests that nurses have mixed attitudes towards people who
      have self-harmed and potentially lack the confidence to provide effective care.
      There is a specific paucity of research in this area for children's nurses.
      DESIGN: A cross-sectional descriptive survey was used to gather data for
      exploration of variables associated with attitudes, confidence, knowledge and
      clinical behavioural intentions of 98 registered children's nurses in a single
      tertiary children's hospital, colocated in a large acute NHS Trust in the UK.
      METHODS: Data were collected over a 4 weeks in 2015, using an online survey tool.
      The predictive effect of several demographic variables was tested on the outcomes
      of attitudes, knowledge, confidence and behavioural intentions, which were
      collected using relevant, previously used outcome measures. RESULTS: Increased
      experience was found to be associated with improved attitudes relating to
      negativity. Previous training in caring for children who had self-harmed was
      found to be associated with improved attitudes around perceived effectiveness of
      their care. Higher academic qualifications and having undertaken previous
      training on self-harm were each found to be associated with increased knowledge
      of self-harm, and increased age was associated with reduced knowledge of self
      harm. CONCLUSIONS: This study provides an initial exploration of variables
      associated with attitudes, knowledge, confidence and behaviour intentions of
      registered children's nurses in relation to caring for CYP who have self-harmed.
      RELEVANCE TO CLINICAL PRACTICE: Targeted training on caring for CYP who have self
      harmed should be considered as a component of continuing education for registered
      children's nurses in the UK to improve the experience and outcomes for this
      patient group.

PMID- 29569382
TI  - Case of lamotrigine-induced drug adverse reaction under tocilizumab treatment
      with clinical and virological features of drug-induced hypersensitivity syndrome.
AB  - The pathological mechanisms and immunological kinetics of drug-induced
      hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6,
      remain unclear. We report a case of drug adverse reaction that does not fulfill
      the diagnostic criteria of DIHS but mimics its characteristic features. Because
      the patient was under anti-IL-6 therapy at the onset, some symptoms typically
      seen in DIHS were absent, such as fever and leukocyte count abnormalities.
      However, the characteristic features of DIHS were clearly observed in the
      subsequent course, including the repeated recurrence of skin rash, prolonged
      liver dysfunction and reactivation of herpes viruses. This case suggested that IL
      6 role at the onset is not a main factor to determine the subsequent
      pathomechanism of DIHS and attention should be paid to the preceding therapy for
      achieving accurate diagnosis.

PMID- 29569383
TI  - Inter-disciplinary cooperation in a physician-staffed emergency medical system.
AB  - BACKGROUND: On-scene management of pre-hospital emergencies is often inter
      disciplinary, involving ground-emergency medical services (EMS), police- and fire
      services, and in Norway general practitioners on-call. This can also be
      supplemented by physician-staffed EMS (P-EMS), utilizing helicopters or rapid
      response vehicles. We hypothesized that P-EMS cooperates extensively with other
      emergency services, and therefore the primary aim of this study was to
      investigate the fraction of inter-disciplinary cooperation between P-EMS and
      other emergency services. METHODS: Retrospective, observational study of primary
      pre-hospital missions with patient contact performed at a Norwegian P-EMS base
      from 01.01.06 to 31.12.15. Descriptive statistics, comparisons using Student's t
      test, and chi-squared test for trend were applied. RESULTS: Inter-disciplinary
      cooperation occurred in 94.3% of the 8580 missions, of which physician-staffed
      EMS cooperated with ground EMS in 92.4%, general practitioner 32.9%, police
      service 11.6% and fire service 11.8%. Trauma constituted 34.4 and cardiac arrest
      14.1% of missions. The mean National Advisory Committee for Aeronautics score was
      4.21 (95% Confidence Interval 4.18-4.24). There was an overall decrease in
      cooperation with general practitioners and the police service (P < 0.001). During
      helicopter missions, we reported a decrease in general practitioner cooperation
      compared to an increase during rapid response car missions (P < 0.001). In
      cardiac arrest cases, cooperation with both general practitioners and the fire
      service increased (P < 0.001). CONCLUSION: Physician-staffed EMS cooperates
      extensively with other professional emergency services, especially ground-EMS. On
      scene cooperation with general practitioners decreased, whereas there was an
      increased cooperation with the fire service in a "first-responder" role during
      cardiac arrest missions.

PMID- 29569385
TI  - Taste impairment in chronic rhinosinusitis.
AB  - BACKGROUND: Though many patients with chronic rhinosinusitis (CRS) describe
      disturbances in smell and taste, there have been no studies specifically
      assessing taste impairment in CRS. This study sought to objectively assess taste
      dysfunction in CRS patients and determine whether taste impairment correlates
      with olfactory dysfunction. Additionally, this investigation sought to determine
      the impact of taste dysfunction on quality of life (QOL) in CRS and identify the
      clinical factors that influence taste. METHODS: Sixty-eight CRS patients were
      prospectively enrolled and completed several QOL surveys in relation to taste,
      smell, overall sinus-specific QOL, and depression. Validated taste strips were
      used to determine gustatory dysfunction pertaining to sweet, sour, salty, and
      bitter. Olfactory testing was assessed using the Sniffin' Sticks Test while both
      Lund-Kennedy and Olfactory Cleft Endoscopy Scoring (OCES) systems were used for
      endoscopic evaluation. RESULTS: The overall prevalence of dysgeusia was 28%, with
      scores significantly lower for sour compared to other subgroups. No correlation
      was observed between taste scores and objective olfactory metrics including
      olfaction tests and OCES. Taste scores were better in younger patients (r = 0.28,
      p = 0.02), female patients (p = 0.004), and never smokers compared to former
      smokers (p = 0.01). Taste scores did not correlate with patient-reported outcome
      measures or CRS disease severity metrics. CONCLUSION: Taste dysfunction is a
      common complaint in CRS. This cohort shows prevalence of gustatory loss to be
      about 28% using ideal normative values. This dysfunction correlated with male
      gender, smoking history, and older age. Taste dysfunction did not correlate with
      measured olfactory outcomes.

PMID- 29569384
TI  - Patterns of Z chromosome divergence among Heliconius species highlight the
      importance of historical demography.
AB  - Sex chromosomes are disproportionately involved in reproductive isolation and
      adaptation. In support of such a "large-X" effect, genome scans between recently
      diverged populations and species pairs often identify distinct patterns of
      divergence on the sex chromosome compared to autosomes. When measures of
      divergence between populations are higher on the sex chromosome compared to
      autosomes, such patterns could be interpreted as evidence for faster divergence
      on the sex chromosome, that is "faster-X", barriers to gene flow on the sex
      chromosome. However, demographic changes can strongly skew divergence estimates
      and are not always taken into consideration. We used 224 whole-genome sequences
      representing 36 populations from two Heliconius butterfly clades (H. erato and H.
      melpomene) to explore patterns of Z chromosome divergence. We show that increased
      divergence compared to equilibrium expectations can in many cases be explained by
      demographic change. Among Heliconius erato populations, for instance, population
      size increase in the ancestral population can explain increased absolute
      divergence measures on the Z chromosome compared to the autosomes, as a result of
      increased ancestral Z chromosome genetic diversity. Nonetheless, we do identify
      increased divergence on the Z chromosome relative to the autosomes in parapatric
      or sympatric species comparisons that imply postzygotic reproductive barriers.
      Using simulations, we show that this is consistent with reduced gene flow on the
      Z chromosome, perhaps due to greater accumulation of incompatibilities. Our work
      demonstrates the importance of taking demography into account to interpret
      patterns of divergence on the Z chromosome, but nonetheless provides evidence to
      support the Z chromosome as a strong barrier to gene flow in incipient Heliconius
      butterfly species.

PMID- 29569386
TI  - Eighteen-month-olds selectively generalize words from accurate speakers to novel
      contexts.
AB  - The present studies examine whether and how 18-month-olds use informants'
      accuracy to acquire novel labels for novel objects and generalize them to a new
      context. In Experiment 1, two speakers made statements about the labels of
      familiar objects. One used accurate labels and the other used inaccurate labels.
      One of these speakers then introduced novel labels for two novel objects. At
      test, toddlers saw those two novel objects and heard an unfamiliar voice say one
      of the labels provided by the speaker. Only toddlers who had heard the novel
      labels introduced by the accurate speaker looked at the appropriate novel object
      above chance. Experiment 2 explored possible mechanisms underlying this
      difference in generalization. Rather than making statements about familiar
      objects' labels, both speakers asked questions about the objects' labels, with
      one speaker using accurate labels and the other using inaccurate labels.
      Toddlers' generalization of novel labels for novel objects was at chance for both
      speakers, suggesting that toddlers do not simply associate hearing the accurate
      label with the reliability of the speaker. We discuss these results in terms of
      potential mechanisms by which children learn and generalize novel labels across
      contexts from speaker reliability.

PMID- 29569387
TI  - A novel functional polymorphism of GSTM3 reduces clear cell renal cell carcinoma
      risk through enhancing its expression by interfering miR-556 binding.
AB  - Dysregulation of glutathione-S-transferase M3 (GSTM3) has been related to clear
      cell renal cell carcinoma (ccRCC) in our former study. GSTM3 plays a pivotal role
      of detoxification and clearance of reactive oxygen species (ROS) in tumour
      tissues. This study aimed to examine: (1) the associations between GSTM3 single
      nucleotide polymorphisms (SNPs) and risk of ccRCC, and (2) the potential
      molecular mechanism accounting for its effects. 5 SNPs in 3'UTR of GSTM3 were
      initially genotyped in 329 cases and 420 healthy controls. A SNP-rs1055259 was
      found to be significantly associated with the susceptibility of ccRCC (OR = 0.59,
      95% CI = 0.41-0.92; P = .019). The minor allele of rs1055259 (G allele) was
      associated with RCC risk. This SNP was predicted to affect microRNA (miR)-556
      binding to 3'UTR of GSTM3 mRNA. To determine the functional impact, plasmid
      constructs carrying different alleles of rs1055259 were created. Compared to
      rs1055259 A-allele constructs, cells transfected with rs1055259 G-allele
      construct had higher transcriptional activity and were less responsive to miR-556
      changes and gene expression. Elevated GSTM3 expression in G-allele cells was
      associated with ROS activity and ccRCC development. Taken together, this study
      indicated that a functional polymorphism of GSTM3 -rs1055259 reduced
      susceptibility of RCC in the Chinese population. It influenced GSTM3 protein
      synthesis by interfering miR-556 binding, subsequently suppressed ROS activity
      and ccRCC progression.

PMID- 29569388
TI  - Antigen-specific airway IL-33 production depends on FcgammaR-mediated
      incorporation of the antigen by alveolar macrophages in sensitized mice.
AB  - Although interleukin (IL)-33 is a candidate for the aggravation of asthma, the
      mechanisms underlying antigen-specific IL-33 production in the lung are unclear.
      Therefore, we analysed the mechanisms in mice. Intra-tracheal administration of
      ovalbumin (OVA) evoked increases in IL-33 and IL-33 mRNA in the lungs of both non
      sensitized and OVA-sensitized mice, and the increases in the sensitized mice were
      significantly higher than in the non-sensitized mice. However, intra-tracheal
      administration of bovine serum albumin did not increase the IL-33 level in the
      OVA-sensitized mice. Depletion of neither mast cells/basophils nor CD4+ cells
      abolished the OVA-induced IL-33 production in sensitized mice, suggesting that
      the antigen recognition leading to the IL-33 production was not related with
      either antigen-specific IgE-bearing mast cells/basophils or memory CD4+ Th2
      cells. When a fluorogenic substrate-labelled OVA (DQ-OVA) was intra-tracheally
      administered, the lung cells of sensitized mice incorporated more DQ-OVA than
      those of non-sensitized mice. The lung cells incorporating DQ-OVA included B
      cells and alveolar macrophages. The allergic IL-33 production was significantly
      reduced by treatment with anti-FcgammaRII/III mAb. Depletion of alveolar
      macrophages by clodronate liposomes significantly suppressed the allergic IL-33
      production, whereas depletion of B-cells by anti-CD20 mAb did not. These results
      suggest that the administered OVA in the lung bound antigen-specific IgG Ab, and
      then alveolar macrophages incorporated the immune complex through FcgammaRII/III
      on the cell surface, resulting in IL-33 production in sensitized mice. The
      mechanisms underlying the antigen-specific IL-33 production may aid in
      development of new pharmacotherapies.

PMID- 29569390
TI  - The fragility of statistically significant findings from randomised controlled
      trials in the urological literature.
AB  - OBJECTIVES: To use the Fragility Index to evaluate the robustness of
      statistically significant findings from urological randomised controlled trials
      (RCTs). MATERIALS AND METHODS: The 'Fragility Index' is defined as the minimum
      number of patients in one arm of a trial whose status would have to change from
      'event' to 'non-event', such that a statistically significant result becomes non
      significant. We identified all RCTs published in four major urology journals
      between 2011 and 2015, and we determined the Fragility Index values for those
      trials reporting statistically significant results of dichotomous outcomes using
      the Fisher's exact test. RESULTS: In all, 332 RCTs were identified, and 41
      studies met the inclusion criteria. The median (interquartile range) Fragility
      Index was 3 (1, 4.5), indicating that an addition of only three alternate events
      to one arm of a typical trial would have eliminated its statistical significance.
      In 27/40 cases (67.5% of cases), the number of patients lost to follow-up was
      larger than its Fragility Index. CONCLUSIONS: The results of urology RCTs that
      study dichotomous outcomes and report statistically significant differences
      between groups are sometimes fragile and depend on few events. Urologists should
      interpret these RCTs cautiously, particularly when the number of participants
      lost to follow-up exceeds the Fragility Index. Routine reporting of Fragility
      Index values alongside P values may provide additional guidance about the
      robustness of statistically significant findings.

PMID- 29569389
TI  - Serenoa repens + selenium + lycopene vs tadalafil 5 mg for the treatment of lower
      urinary tract symptoms secondary to benign prostatic obstruction: a Phase IV, non
      inferiority, open-label, clinical study (SPRITE study).
AB  - OBJECTIVE: To compare in a randomised, open-label, non-inferiority clinical
      study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) +
      lycopene (Ly) (SeR-Se-Ly) therapy vs tadalafil 5 mg in men with lower urinary
      tract symptoms (LUTS). PATIENTS AND METHODS: From May 2015 to January 2017, 427
      patients were enrolled in 21 different centres (International Standard Randomised
      Controlled Trial Number Register [ISRCTN] 73316039). Inclusion criteria included:
      age between 50 and 80 years, International Prostate Symptom Score (IPSS) >=12,
      maximum urinary flow rate (Qmax ) <= 15 mL/s, and post-void residual (PVR) <100
      mL. Patients were randomised into two groups in a 2:1 ratio: Group A (SeR-Se-Ly,
      1 tablet daily for 6 months) and Group B (tadalafil 5 mg, 1 tablet daily for 6
      months). The primary endpoint of the study was the non-inferior variation in the
      IPSS and Qmax in Group A vs Group B after 6 months of treatment. RESULTS: In all,
      404 patients completed the full protocol. When comparing both therapies, Group A
      was statistically not inferior to Group B considering the median change in IPSS (
      3.0 vs -3.0; P < 0.01), IPSS quality of life (-2.0 vs -2.0; P < 0.05), and Qmax
      (2.0 vs 2.0 mL/s; P < 0.01). We found statistically significant differences in
      the increase of at least 3 points in Qmax (38.2% vs 28.1%; P = 0.04) and of at
      least 30% of Qmax (39.2% vs 27.3%; P < 0.01) in Group A compared to Group B. The
      percentage of patients with an increase of at least 3 points in the IPSS and a
      decrease of at least 25% of the IPSS was not statistically different between the
      two groups. For adverse events, four patients in Group A (1.44%) and 10 in Group
      B (7.81%) (P < 0.05) reported side-effects. CONCLUSION: We have shown that
      treatment with SeR-Se-Ly was not inferior to tadalafil 5 mg for improving IPSS
      and Qmax in men with LUTS.

PMID- 29569391
TI  - Layer-by-layer buildup of polysaccharide-containing films: Physico-chemical
      properties and mesenchymal stem cells adhesion.
AB  - Layer-by-Layer assembled polyelectrolyte films offer the opportunity to control
      cell attachment and behavior on solid surfaces. In the present study, multilayer
      films based on negatively charged biopolymers (pectin, dextran sulfate,
      carboxymethylcellulose) and positively charged polysaccharide chitosan or
      synthetic polyelectrolyte polyethyleneimine has been prepared and evaluated.
      Physico-chemical properties of the formed multilayer films, including their
      growth, morphology, wettability, stability, and mechanical properties, have been
      studied. We demonstrated that chitosan-containing films are characterized by the
      linear growth, the defect-free surface, and predominantly viscoelastic
      properties. When chitosan is substituted for the polyethyleneimine in the
      multilayer system, the properties of the formed films are significantly altered:
      the rigidity and surface roughness increases, the film growth acquires the
      exponential character. The multilayer films were subsequently used for culturing
      mesenchymal stem cells. It has been determined that stem cells effectively
      adhered to chitosan-containing films and formed on them the monolayer culture of
      fibroblast-like cells with high viability. Our results show that cell attachment
      is a complex process which is not only governed by the surface functionality
      because one of the key parameter effects on cell adhesion is the stiffness of
      polyelectrolyte multilayer films. We therefore propose our Layer-by-Layer films
      for applications in tissue engineering. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 2093-2104, 2018.

PMID- 29569392
TI  - Factors affecting the dose of methadone among patients receiving methadone
      maintenance therapy in Taiwan.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) has been shown to be an
      effective therapeutic strategy for opioid users. This study aimed to investigate
      the predictive effect of clinically predominant sleep disturbance (CPSD) on the
      dose of methadone among opiate users receiving MMT during a follow-up period of 6
      years in Taiwan. METHODS: This retrospective study included 1,290 individuals
      with opioid dependence who visited our MMT clinic for the first time. Generalized
      estimating equations were used to analyze the effect of CPSD on the daily dose of
      methadone by controlling for the effects of demographic and MMT characteristics.
      RESULTS: A total of 469 (36.4%) participants were comorbid with CPSD. After
      controlling for the effects of demographic and MMT characteristics, the
      participants comorbid with CPSD had a higher dose of daily methadone than those
      without CPSD (estimate: 7.03, p < .001). Furthermore, younger age (estimate: 
      1.22, p < .001), older age at initial MMT (estimate: .44, p < .001), lower
      educational level (estimate: -.90, p = .003) and lower attendance rates
      (estimate: -.14, p = .033) are significantly related to higher doses of daily
      methadone. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our study provided a
      naturalistic observation of the cohort for long period, along with a large sample
      size which could reflect clinical practice in the real world. We reported that a
      higher daily dose of methadone was significantly associated with CPSD after
      controlling for the effects of other factors. CPSD should be routinely surveyed
      among heroin users receiving MMT. (Am J Addict 2018;27:225-230).

PMID- 29569393
TI  - Wnt and Notch signaling pathways in calcium phosphate-enhanced osteogenic
      differentiation: A pilot study.
AB  - Calcium phosphate (CaP) ceramics are being increasingly used to repair critical
      bone defect for biocompatibility, biosafety, porous structure and osteoinduction.
      Wnt and Notch signaling pathways are conservative and classic signaling pathways
      regulating osteogenic differentiation of bone marrow mesenchymal stromal cells
      (BMSCs). In this study, we evaluated the expression of Wnt, Notch signal pathways
      and osteogenic related genes of BMSCs with and without Wnt pathway inhibitor DKK1
      on CaP ceramics in vitro by real-time RT-PCR. Also, we evaluated new bone
      formation after implantation of CaP ceramics in vivo. The in vitro culture
      displayed the expression of Wnt, Notch signaling pathways and osteogenic related
      genes was increased at first and then declined. After adding DKK1 to the culture,
      the expression was decreased. The in vivo implantation showed significant bone
      formation on CaP ceramics. These findings reveal that Wnt and Notch signaling
      pathways play important roles in the CaP-enhanced osteogenic differentiation but
      the mechanism of synergistic effect needs to be further explored. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29569394
TI  - The bean alpha-amylase inhibitor alphaAI-1 in genetically modified chickpea seeds
      does not harm parasitoid wasps.
AB  - BACKGROUND: Legumes have been genetically engineered to express alpha-amylase
      inhibitor 1 (alphaAI-1) from common bean in their seeds. Whereas the genetically
      modified (GM) seeds are immune to multiple bruchid pest species, the cosmopolitan
      bruchid Acanthoscelides obtectus is tolerant to alphaAI-1 and their larvae
      develop normally inside the seeds. Hymenopteran bruchid parasitoids, the most
      important natural enemies of bruchids, might thus be exposed to alphaAI-1 when
      attacking A. obtectus larvae developing inside GM seeds. Exposure might reduce
      parasitoid fitness, resulting in a decline in the natural control of A. obtectus,
      and thus promote the spread of this pest. We investigated the impact of the
      presence of alphaAI-1 in legume seeds on parasitoid fitness in tritrophic
      experiments with alphaAI-1 GM or non-GM chickpea seeds, A. obtectus, and three
      parasitoid species. Additionally, we investigated the exposure of parasitoids to
      alphaAI-1 using a fourth, highly sensitive parasitoid species. RESULTS:
      Parasitoid fitness was not affected when A. obtectus was used in GM chickpea
      seeds as hosts, and this lack of effects was probably attributable to the fact
      that exposure of the parasitoids to alphaAI-1 was negligible. CONCLUSION: We
      conclude that the release of GM chickpeas containing alphaAI-1 should not harm
      this important group of non-target insects. (c) 2018 Society of Chemical
      Industry.

PMID- 29569395
TI  - The art and science of statistical predictions: does a picture need a thousand
      words?

PMID- 29569396
TI  - Time for global scale-up, not randomized trials, of uterine balloon tamponade for
      postpartum hemorrhage.

PMID- 29569397
TI  - Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with
      generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety
      analyses of a 52-week, phase 3, multicenter, open-label study.
AB  - Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the
      rare and severe subtypes of psoriasis, which are often difficult to treat. The
      aim of this phase 3, open-label study was to evaluate efficacy and safety of
      guselkumab, a human interleukin-23 monoclonal antibody, in Japanese patients with
      GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11)
      patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20,
      patients were escalated to 100 mg q8w if they met the dose escalation criteria.
      The primary end-point was the proportion of patients achieving treatment success
      (Clinical Global Impression score of "very much improved", "much improved" or
      "minimally improved") at week 16. Safety evaluations included assessment of
      treatment-emergent adverse events (TEAE) through week 52. At week 16, the
      proportions of GPP and EP patients achieving treatment success were 77.8% (7/9)
      and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently
      showed improvement in responses of secondary end-points such as Psoriasis Area
      and Severity Index, Investigator's Global Assessment, Japanese Dermatological
      Association severity index and improvement in body surface area involvement.
      Improvements in quality of life, as assessed by the Dermatology Life Quality
      Index, were also observed through week 52. The most commonly reported TEAE was
      nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those
      observed previously in other studies. In conclusion, guselkumab treatment
      demonstrated efficacy and showed no safety concerns in Japanese patients with GPP
      and EP through week 52.

PMID- 29569398
TI  - The association of peri-operative scores, including frailty, with outcomes after
      unscheduled surgery.
AB  - Postoperative hospital stay is longer for frail, older patients, who are more
      likely to experience prolonged postoperative morbidity and reduced long-term
      survival. We recorded in-hospital mortality, morbidity and length of stay for 164
      patients aged at least 65 years after unscheduled surgery. We evaluated pre
      operative frailty with the 7-point Clinical Frailty Scale: 81 patients were 'not
      vulnerable' (frailty score 1-3) and 83 were 'vulnerable or frail' (frailty score
      ? 4), with mean (SD) ages of 74.7 (7.5) years vs. 79.4 (8.3) years, respectively,
      p < 0.001. Within 30 postoperative days 8/164 (5%) patients died, all with
      frailty scores ? 4, p = 0.007. Postoperative morbidity was less frequent in
      patients categorised as 'not vulnerable' on four out of the six days it was
      measured (days 3, 5, 8, 14, 23, 28). Median (IQR [range]) postoperative stay was
      9 (6-18 [2-221]) days for patients with frailty scores 1-3, and 22 (12-33 [2
      270]) days for patients with score ? 4, p < 0.001. Four variables independently
      associated with hospital discharge, hazard ratio (95%CI): E-POSSUM, 0.74 (0.60
      0.92), p = 0.007; ASA 2, 0.35 (0.13-0.98), p = 0.046, ASA 3, 0.17 (0.06-0.47), p
      = 0.001 and ASA 4/5, 0.08 (0.02-0.28), p < 0.001; operative severity 'major +',
      0.69 (0.41-1.08), p = 0.10 and the Surgical Outcome Risk Tool, 7.75 (0.81-74.40),
      p = 0.08.

PMID- 29569400
TI  - Increased serum levels of high mobility group protein B1 and calprotectin in pre
      eclampsia.
AB  - OBJECTIVE: To determine whether women with pre-eclampsia have serum levels of
      biomarkers indicative of an elevated systemic inflammatory response. METHOD: The
      present cross-sectional study was conducted among pregnant women either with pre
      eclampsia or without pre-eclampsia who were recruited at a single Chinese
      hospital between August 1, 2016, and April 30, 2017. Eligible women had no
      history of acute or chronic inflammation. Serum concentrations of high mobility
      group protein B1 (HMG-1), calprotectin, and Toll-like receptor 4 (TLR4) were
      measured and compared. RESULTS: There were 55 patients included (25 with pre
      eclampsia and 30 without). The mean serum concentration of calprotectin was
      2656.76 +/- 1724.56 MUg/L in the pre-eclampsia group versus 1877.33 +/- 905.69
      MUg/L in the control group (P=0.036). Among patients with pre-eclampsia, elevated
      calprotectin levels were positively associated with the duration of hypertension
      in pregnancy (P=0.031) and were negatively associated with pregnancy duration at
      delivery (P=0.035). The mean serum concentration of HMG-1 was 72.48 +/- 27.57
      MUg/L in the pre-eclampsia group versus 57.57 +/- 20.07 MUg/L in the control
      group (P=0.017). The mean serum concentration of TLR4 was 22.83 +/- 8.46 MUg/L in
      the pre-eclampsia group versus 18.83 +/- 6.79 MUg/L in the control group
      (P=0.057). CONCLUSION: Elevated levels of HMG-1 and calprotectin could reflect an
      excessive systemic inflammatory response in pre-eclampsia.

PMID- 29569399
TI  - Identification of clinically relevant phenotypes in patients with Ebstein
      anomaly.
AB  - BACKGROUND: Ebstein anomaly (EA) is a heterogeneous congenital heart defect
      (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities,
      resulting in a wide range of clinical outcomes. HYPOTHESIS: Phenotypic
      characterization of EA patients has the potential to identify variables that
      influence prognosis and subgroups with distinct contributing factors. METHODS: A
      comprehensive cross-sectional phenotypic characterization of 147 EA patients from
      one of the main referral institutions for CHD in Colombia was carried out. The
      most prevalent comorbidities and distinct subgroups within the patient cohort
      were identified through cluster analysis. RESULTS: The most prevalent cardiac
      comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White
      syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%).
      Cluster analysis showed that patients can be classified into 2 distinct subgroups
      with defined phenotypes that determine disease severity and survival. Patients in
      cluster 1 represented a particularly homogeneous subgroup with a milder spectrum
      of disease, including only patients with WPW and/or supraventricular tachycardia
      (SVT). Cluster 2 included patients with more diverse cardiovascular
      comorbidities. CONCLUSIONS: This study represents one of the largest phenotypic
      characterizations of EA patients reported. The data show that EA is a
      heterogeneous disease, very frequently associated with cardiovascular and
      noncardiovascular comorbidities. Patients with WPW and SVT represent a
      homogeneous subgroup that presents with a less severe spectrum of disease and
      better survival when adequately managed. This should be considered when searching
      for genetic causes of EA and in the clinical setting.

PMID- 29569401
TI  - Sedative and cardiorespiratory effects of low doses of xylazine with and without
      acepromazine in Nordestino donkeys.
AB  - BACKGROUND: Information on appropriate protocols for sedation of Nordestino
      donkeys is scarce. OBJECTIVES: To evaluate the sedative and cardiorespiratory
      effects of low doses of intravenous (i.v.) xylazine with and without acepromazine
      in 'Nordestino' donkeys. STUDY DESIGN: Seven healthy female Nordestino donkeys
      (150 +/- 18 kg) were included in this blinded, randomised, crossover experiment.
      METHODS: Four treatments were administered, consisting of two i.v. injections, at
      baseline (T0, 1st injection) and 15 min later (T15, 2nd injection). Treatments
      included acepromazine 0.05 mg/kg bwt + saline (AS), saline + xylazine 0.5 mg/kg
      bwt (SX0.5), acepromazine + xylazine 0.25 mg/kg bwt (AX0.25) or acepromazine +
      xylazine 0.5 mg/kg bwt (AX0.5). Sedative and cardiorespiratory parameters were
      evaluated before T0 and 15, 20, 30, 45, 60, 75 and 90 min after treatment. Degree
      [height of head above ground (HHAG)] and quality of sedation [ataxia, responses
      to stimuli and visual analogue scale (VAS) scoring] and respiratory rate were
      evaluated by the main investigator in situ, and heart rate was measured by an
      assistant investigator. Three experienced evaluators assessed videos for ataxia
      and responses to stimuli. Normal data were analysed by repeated measures ANOVA,
      and non-normal by Kruskal-Wallis (P<0.05). RESULTS: HHAG was lower than baseline
      for 15 min after xylazine administration in AX0.25 and for 30 min in SX0.5 and
      AX0.5 groups. All treatments with xylazine increased VAS and ataxia scores in
      situ for 15 min after xylazine administration, with no differences between
      groups. Ataxia scores in situ were higher in SX0.5 and AX0.5 groups than AS for
      15 and 30 min after xylazine administration, respectively. MAIN LIMITATIONS:
      Absence of a negative control group (saline-saline). CONCLUSION: Acepromazine
      added to xylazine at 0.25 mg/kg bwt produced briefer and milder sedation than
      xylazine at 0.5 mg/kg bwt.

PMID- 29569403
TI  - Generalizability of the findings from a randomized controlled trial of a web
      based substance use disorder intervention.
AB  - BACKGROUND AND OBJECTIVES: There is growing concern regarding the
      generalizability of findings from randomized controlled trials (RCTs) of
      interventions for substance use disorders (SUDs). This study used a selection
      model approach to assess and improve the generalizability of an evaluation for a
      web-based SUD intervention by making the trial sample resemble the target
      population. METHODS: The sample of the web-based SUD intervention (Therapeutic
      Education System vs. Treatment-as-usual; n = 507) was compared with the target
      population of SUD treatment-seeking individuals from the Treatment Episodes Data
      Set-Admissions (TEDS-A). Using weights based on the probabilities of RCT
      participation, we computed weighted treatment effects on retention and
      abstinence. RESULTS: Substantial differences between the RCT sample and the
      target population was demonstrated in significant difference in the mean
      propensity scores (1.62 standard deviations at p < .001). The population effect
      on abstinence (12 weeks and 6 months) was statistically insignificant after
      weighting the data with the generalizability weight. DISCUSSIONS AND CONCLUSIONS:
      Generalizability of the findings from the RCT could be limited when the RCT
      sample does not well represent the target population. SCIENTIFIC SIGNIFICANCE:
      Application of generalizability weights can be a potentially useful tool to
      improve generalizability of RCT findings. (Am J Addict 2018;27:231-237).

PMID- 29569402
TI  - Use of neutrophil-lymphocyte ratio for risk stratification and relationship with
      time in therapeutic range in patients with nonvalvular atrial fibrillation: A
      pilot study.
AB  - BACKGROUND: Atrial fibrillation is one of the most common abnormal heart rhythms.
      Neutrophil-lymphocyte ratio (NLR) has emerged as a potential marker for the level
      of inflammation in cardiac disorders. HYPOTHESIS: NLR might be associated with
      thrombosis and bleeding risk scores and might predict cardioembolic risk in
      nonvalvular atrial fibrillation (NVAF) patients within the therapeutic
      international normalized ratio (INR). METHODS: We enrolled 272 patients taking
      warfarin for NVAF and classified them into 2 groups: Group A consisted of
      patients (n = 132) whose time in therapeutic range (TTR) was >=65%, and Group B
      comprised patients (n = 139) whose TTR was <65%. RESULTS: NLR values were higher
      in group B than in group A (P < 0.0001). Patients classified as high risk
      according to CHA2 DS2 -VASc score had significantly higher NLR levels (P = 0.002)
      than those classified as low and intermediate risk. Furthermore, NLR levels were
      significantly correlated with CHA2 DS2 -VASc and HAS-BLED scores (P < 0.001 and P
      < 0.0001, respectively). NLR predicted patients within therapeutic INR range (TTR
      >=65%) with sensitivity of 81% and specificity of 71% in a receiver operator
      characteristic curve analysis, using a cutoff value of 2.17. Area under the curve
      for NLR was 0.81 (P < 0.0001). CONCLUSIONS: To our knowledge, this is the first
      study showing correlation of NLR with both CHA2 DS2 -VASc and HAS-BLED risk
      scores. NLR might represent a useful marker to identify patients with high risks
      of stroke and bleeding and may have predictive value in identifying patients
      within the therapeutic INR range.

PMID- 29569404
TI  - Clinical predictors of Alzheimer's disease progression.
AB  - AIM: Rates of disease progression differ among patients with Alzheimer's disease
      (AD), but prognostic predictions remain a challenge. We carried out a clinic
      based retrospective study to investigate the clinical factors for AD progression.
      METHODS: The 748 AD patients, who attended our hospital for >1 year and were
      given the Mini-Mental State Examination (MMSE) at least three times, were divided
      into three groups according to the annual change rate of MMSE score (G):
      Aggravater group (G < -2), Stabler group (-2 <= G <= 2) and Improver group (2 <
      G). We compared the three groups on cognitive, affective and activities of daily
      living functions, response to medication, clinical fluctuations, serum levels of
      metabolic factors, and neuroimaging data. RESULTS: We found no significant
      differences in age, sex, educational attainment or body mass index across the
      groups. The Aggravater group showed better baseline MMSE (P < 0.01) and Abe's
      behavioral and psychological symptoms of dementia (P < 0.01) scores than the
      Improver group, but its MMSE improvement after drug treatment was the worst among
      the three groups (P < 0.01 vs Stabler/Improver). Fluctuations in MMSE (P < 0.01),
      apathy scale (P < 0.05) and activities of daily living (P < 0.01) scores were
      smaller in the Improver group than in the Aggravater or Stabler groups. Serum
      docosahexaenoic acid levels tended to be lower (trend P < 0.05) and voxel-based
      specific regional analysis system for Alzheimer's disease Z-scores tended to be
      higher (trend P < 0.05) in the Improver group than in the Stabler or Aggravater
      groups. CONCLUSIONS: Initial responses to medication, fluctuations in cognitive,
      affective and activities of daily living functions, serum docosahexaenoic acid
      levels, and medial temporal atrophy are clinical factors related to AD prognosis.
      Geriatr Gerontol Int 2018; 18: 929-936.

PMID- 29569405
TI  - Digoxin use and lower risk of 30-day all-cause readmission in older patients with
      heart failure and reduced ejection fraction receiving beta-blockers.
AB  - BACKGROUND: Digoxin use has been associated with a lower risk of 30-day all-cause
      admission and readmission in patients with heart failure and reduced ejection
      fraction (HFrEF). HYPOTHESIS: Digoxin use will be associated with improved
      outcomes in patients with HFrEF receiving beta-blockers. METHODS: Of the 3076
      hospitalized Medicare beneficiaries with HFrEF (EF <45%), 1046 received a
      discharge prescription for beta-blockers, of which 634 were not on digoxin. Of
      the 634, 204 received a new discharge prescription for digoxin. Propensity scores
      for digoxin use, estimated for each of the 634 patients, were used to assemble a
      matched cohort of 167 pairs of patients receiving and not receiving digoxin,
      balanced on 30 baseline characteristics. Matched patients (n = 334) had a mean
      age of 74 years and were 46% female and 30% African American. RESULTS: 30-day all
      cause readmission occurred in 15% and 27% of those receiving and not receiving
      digoxin, respectively (hazard ratio [HR]: 0.51, 95% confidence interval [CI]:
      0.31-0.83, P = 0.007). This beneficial association persisted during 4 years of
      follow-up (HR: 0.72, 95% CI: 0.57-0.92, P = 0.008). Digoxin use was also
      associated with a lower risk of the combined endpoint of all-cause readmission or
      all-cause mortality at 30 days (HR: 0.54, 95% CI: 0.34-0.86, P = 0.009) and at 4
      years (HR: 0.76, 95% CI: 0.61-0.96, P = 0.020). CONCLUSIONS: In hospitalized
      patients with HFrEF receiving beta-blockers, digoxin use was associated with a
      lower risk of 30-day all-cause readmission but not mortality, which persisted
      during longer follow-up.

PMID- 29569406
TI  - An ecological perspective on managing weeds during the great selection for
      herbicide resistance.
AB  - More than 70 years after modern agriculture declared a 'war on weeds', they
      continue to thrive and suppress crop yields. Viewing weeds as an enemy that can
      be defeated if only a powerful enough technology can be deployed is a losing
      proposition. The latest evidence for the inadequacy of this approach, rampant
      evolution of multiple herbicide-resistant weed genotypes and dwindling options
      for chemical control in many production systems, should be seen as an urgent
      message to all those concerned with the science and practice of weed management:
      we need another way of thinking about the weed resistance issue. Fortunately, the
      theoretical and practical foundation of this alternative approach, ecological
      weed management, has been in development for decades. Here, we use Barry
      Commoner's laws of ecology as a conceptual frame for a review of some of the
      fundamental concepts of ecological weed management. (c) 2018 Society of Chemical
      Industry.

PMID- 29569408
TI  - Chairman's introduction.

PMID- 29569409
TI  - Serotonergic compounds in panic disorder, obsessive-compulsive disorder and
      anxious depression: A concise review.
AB  - The recognition that antidepressants are effective in panic and anxiety disorders
      had led to the evaluation of drugs selective for serotonin uptake in an attempt
      to dissect the neurotransmitters responsible for panic disorder. Fluvoxamine is
      the best studied of the selective serotonin reuptake inhibitors (SSRIs) and
      recent double-blind studies have confirmed earlier findings showing a reduced
      number and duration of panic attacks. In addition, fluvoxamine attenuates the
      'accessory symptoms' of panic disorder such as depression and anxiety. Fluoxetine
      has only been evaluated in open trials, although these results are generally
      positive. Paroxetine has shown similar efficacy to clomipramine in a large,
      controlled study, although the other SSRIs have seldom been investigated.
      Fluvoxamine lacks the activating properties possessed by some SSRIs and this also
      makes it a useful candidate for the treatment of anxious depression. The efficacy
      of fluvoxamine in obsessive-compulsive disorder has been established in several
      double-blind, placebo-controlled trials. In clinical terms, fluvoxamine is
      approximately as effective as clomipramine, but with a decidedly better adverse
      event profile. Fluoxetine has also proved effective in obsessive-compulsive
      disorder, although a recent meta-analysis suggests that fluvoxamine may be
      somewhat more effective. The other SSRIs have not been sufficiently well studied
      to justify conclusive statements.

PMID- 29569410
TI  - Do SSRIs differ in their antidepressant efficacy.
AB  - Selective serotonin reuptake inhibitors (SSRIs) have been extensively studied
      worldwide and show at least equivalent efficacy to the tricyclic antidepressants
      (TCAs). Some of the SSRIs have demonstrated superior efficacy to TCAs in a number
      of subgroups including patients with severe depression, suicidal thoughts or
      depression associated with anxiety. There is currently a lack of direct
      comparative data between the different SSRIs, although the few studies which are
      available indicate overall equal efficacy. However, the pharmacodynamic and
      pharmacokinetic characteristics may result in different side-effects which might,
      in turn, lead to a characteristic pattern of use.

PMID- 29569407
TI  - Neurotensin and neurotensin receptor 1 mRNA expression in song-control regions
      changes during development in male zebra finches.
AB  - Learned vocalizations are important for communication in some vertebrate taxa.
      The neural circuitry for the learning and production of vocalizations is well
      known in songbirds, many of which learn songs initially during a critical period
      early in life. Dopamine is essential for motor learning, including song learning,
      and dopamine-related measures change throughout development in song-control
      regions such as HVC, the lateral magnocellular nucleus of the anterior
      nidopallium (LMAN), Area X, and the robust nucleus of the arcopallium (RA). In
      mammals, the neuropeptide neurotensin strongly interacts with dopamine signaling.
      This study investigated a potential role for the neurotensin system in song
      learning by examining how neurotensin (Nts) and neurotensin receptor 1 (Ntsr1)
      expression change throughout development. Nts and Ntsr1 mRNA expression was
      analyzed in song-control regions of male zebra finches in four stages of the song
      learning process: pre-subsong (25 days posthatch; dph), subsong (45 dph), plastic
      song (60 dph), and crystallized song (130 dph). Nts expression in LMAN during the
      subsong stage was lower compared to other time points. Ntsr1 expression was
      highest in HVC, Area X, and RA during the pre-subsong stage. Opposite and
      complementary expression patterns for the two genes in song nuclei and across the
      whole brain suggest distinct roles for regions that produce and receive Nts. The
      expression changes at crucial time points for song development are similar to
      changes observed in dopamine studies and suggest Nts may be involved in the
      process of vocal learning. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol 78:
      671-686, 2018.

PMID- 29569411
TI  - Comparing SSRIs: From chemistry to clinical choice.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely accepted as the best
      available treatment for most forms of depression. However, to date, there has
      been little attempt to differentiate between the members of this class of drugs.
      Since, unlike the tricyclic antidepressants, the SSRIs have very different
      chemical structures, it is not unexpected that they may have different
      pharmacological properties. These differences in pharmacology may, in turn, be
      expressed in varying pharmacokinetic, efficacy, safety and tolerability profiles
      which mean that the SSRIs may be a less homogeneous class of compounds than is
      generally assumed. This review analyses the differences between the SSRIs with
      the intention of helping the practising clinician to select the most appropriate
      drug for a particular patient.

PMID- 29569412
TI  - Comparative behavioural toxicity of the selective serotonin reuptake inhibitors.
AB  - The psychopharmacological profiles of several selective serotonin reuptake
      inhibitors (SSRIs) were compared and their behavioural toxicity contrasted both
      to placebo and the tricyclic antidepressants dothiepin and amitriptyline. On
      measures of central nervous system arousal (critical flicker fusion), psychomotor
      speed (choice reaction time), skilled performance (compensatory tracking) and
      subjective ratings of sedation (line analogue rating scales), the tricyclic
      compounds clearly impaired performance and led to higher ratings of sedation.
      While the SSRIs were generally clear of these gross effects, there were
      quantifiable differences between the compounds, seen mainly as an increase in
      central nervous system arousal. It remains to be established whether these minor
      differences have any clinical relevance.

PMID- 29569413
TI  - Differential costs of treatment of depression with SSRIs.
AB  - Although the field of economic analysis of mental health care is still in
      development, several issues are now well established. For example, it is
      generally accepted that the treatment costs for depression are significant, with
      estimates for the US ranging up to US$43.7 billion. This includes only US$12.4
      billion for the costs of treating the patients with depression; the remaining
      costs are from lost working days, lost income due to suicides, and lost
      productivity. The high risk of recurrence and chronicity also leads to high
      direct health care costs. In particular, the frequent and long hospitalizations
      required for severe depression have an enormous impact in economic terms. The
      other main costs are related to drug and psychotherapy, and the treatment of side
      effects, which are particularly pronounced with the tricyclic antidepressants.
      Preliminary analyses indicate that the differential tolerability of the current
      selective serotonin reuptake inhibitors (SSRIs) can also give rise to differences
      in total costs of treatment. Thus, it can be hypothesized that the relatively
      favourable side-effect profile of the SSRI fluvoxamine may have positive economic
      consequences, especially as it is one of the lower priced drugs in this class.
      Further research based on primary data is needed to substantiate these benefits.

PMID- 29569414
TI  - SSRI differentiation: Pharmacology and pharmacokinetics.
AB  - Although the acute pharmacology properties of antidepressants is predominantly
      due to their presynaptic action, their therapeutic activity is believed to derive
      from adaptive post-synaptic changes in monoaminergic neurones. The selective
      serotonin reuptake inhibitors (SSRIs) exhibit differences in potency at
      inhibiting serotonin reuptake, although the differences do not correlate with
      clinical posology. There are also differences in their effects on
      neurotransmitter receptors; paroxetine has a slight affinity for muscarinic
      cholinergic receptors whilst citalopram has a slight affinity for histamine-H1
      receptors. These properties may be related to clinical adverse effects. The
      pharmacokinetic profiles of the SSRIs show many differences. Whilst fluvoxamine,
      paroxetine and citalopram are metabolized to inactive products, fluoxetine is
      metabolized to norfluoxetine which is pharmacologically active and, like its
      parent compound, has a long half-life. Fluvoxamine is less protein-bound than the
      other SSRIs and sertraline is only well absorbed when taken with food.
      Differences are also apparent in the suitability of individual SSRIs in special
      patient groups. There has been considerable speculation over the inhibition of
      cytochrome P450 isoenzymes which are responsible for the metabolism of SSRIs and
      other drugs. In clinical practice, the differences between the SSRIs in this
      respect are probably of limited importance. However, it is worthwhile that
      clinicians be made aware of possible interactions between drugs that act as
      inhibitors or substrates of the hepatic cytochrome P450 system.

PMID- 29569415
TI  - Comparative safety and tolerability of selective serotonin reuptake inhibitors.
AB  - The selective serotonin reuptake inhibitors (SSRIs) have the best established
      tolerance and safety profile of the available antidepressants. Evidence for this
      conclusion comes from controlled clinical trials, post-marketing surveillance,
      prescription audits and case reports. Comparative studies are sparse within the
      class of SSRIs, and methodological differences between studies are problematic,
      yet certain differences emerge in tolerability when comparing placebo-adjusted
      incidence rates for the most common adverse events. Fluoxetine commonly produces
      nervousness, anxiety, insomnia and headache. Sexual dysfunction is more common
      with sertraline. Dry mouth can occur from paroxetine, and gastrointestinal
      effects (cramps, diarrhoea) from sertraline. The incidence of nausea appears to
      be no greater for any particular drug, especially after several weeks of
      treatment. Hyponatraemia and extrapyramidal side effects are rare events reported
      with all SSRIs. General guidelines are given for choosing an initial SSRI
      according to adverse effect profile; however, inter-subject variability exists in
      the expression of adverse effects, as well as intra-subject variability during
      treatment, suggesting the development of pharmacodynamic tolerance. Thus,
      rational selection of an SSRI on the basis of comparative tolerability is
      possible, but largely empirical without further scientific evidence from clinical
      trials specifically designed to differentiate drugs according to their adverse
      effect profile.

PMID- 29569416
TI  - History of burning mouth syndrome (1800-1950): A review.
AB  - This medical history historic literature review aims at understanding the
      evolution of the medical existence of burning mouth syndrome (BMS) over times.
      Three historic research tools were used (Medic@, IndexCat, Gallica) with several
      keywords, exploring the years 1800-1950. One hundred and fifty documents were
      obtained dating from 1803 to 1937, including 55 reviews, 44 original articles, 40
      quotations, and 11 medical dictionaries. A total of 199 cases of BMS were
      reported which allowed for a narrative review of the early history of BMS (1800
      1950). This review spans from the description of the first clinical cases by
      several authors in Europe to the creation of the syndrome by the French Academy
      of Medicine, its intellectual sponsorship by the emerging discipline of
      neuropsychiatry, to its subsequent evolution until the conceptual shift of the
      American authors. A better knowledge of the evolution of the nosology of BMS
      throughout history should bring a better understanding of current approaches for
      treating such an affection.

PMID- 29569417
TI  - Dermoscopy features of atypical fibroxanthoma: A multicenter study of the
      International Dermoscopy Society.
AB  - BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical
      fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma
      lesions were compared with a control group with non-melanoma skin cancer.
      RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in
      men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated
      (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%).
      Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%)
      structureless areas and irregular linear vessels (43%). A series of features
      achieved statistical significance when comparing atypical fibroxanthoma with non
      melanoma skin cancer. The presence of red and white structureless areas and white
      lines, and the absence of yellowish-white opaque scales, hairpin vessels and
      arborising vessels were predictive of atypical fibroxanthoma in univariate
      analysis. However, when squamous cell carcinoma was excluded from the analysis,
      none of the criteria achieved statistical significance. When basal cell carcinoma
      was excluded, three variables achieved statistical significance in predicting
      atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish
      white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas
      seem to be barely distinguishable from basal cell carcinoma dermoscopically, but
      they are more easily distinguishable from a well to moderately differentiated
      squamous cell carcinoma. A histopathological examination is needed for the final
      diagnosis.

PMID- 29569418
TI  - Monitoring of pH and temperature of neuropathic diabetic and nondiabetic foot
      ulcers for 12 weeks: An observational study.
AB  - Wound bed assessment is largely reliant on subjective interpretation without
      recourse to objective tools or biomarkers. The identification of a point of care,
      reliable biomarker would enhance assessment and ultimately clinical decision
      making. Two potentially emerging wound biomarkers exist: surface pH and surface
      temperature. To date, knowledge of their use has been predominantly in wound
      prevention, in vitro studies and single time measurements. Our objective was to
      determine surface pH, size, and surface temperature in noninfected, neuropathic
      foot ulcers at baseline and at 12 weeks. 50 patients (68% [n = 34] had diabetes)
      participated. Mean baseline pH of wounds was 6.95 (SD 1.01); temperature 30.91 
      degrees C (SD 3.00); and size 0.82 cm2 (SD 0.61). After 12 weeks, 26% (n = 13)
      were lost to follow-up, 50% (n = 25) had healed. Of the remaining patients, mean
      pH was 6.72 (SD 0.54); temperature 30.88  degrees C (SD 2.97), and size 0.13 cm2
      (SD 0.13). We have provided baseline values for pH and temperature of
      noninfected, neuropathic diabetic, and nondiabetic foot ulceration. Further
      studies in a larger cohort are warranted to determine if temperature and or pH
      are indicative of a healing or nonhealing state.

PMID- 29569419
TI  - Patients with perianal Crohn's fistulas experience delays in accessing anti-TNF
      therapy due to slow recognition, diagnosis and integration of specialist
      services: lessons learned from three referral centres.
AB  - AIM: Crohn's anal fistula should be managed by a multidisciplinary team. There is
      no clearly defined 'patient pathway' from presentation to treatment. The aim of
      this study was to describe the patient route from presentation with symptomatic
      Crohn's anal fistula to starting anti-tumour necrosis factor (anti-TNF) therapy.
      METHOD: Case note review was undertaken at three hospitals with established
      inflammatory bowel disease services. Patients with Crohn's anal fistula
      presenting between 2010 and 2015 were identified through clinical coding and
      local databases. Baseline demographics were captured. Patient records were
      interrogated to identify route of access, and clinical contacts during the
      patient pathway. RESULTS: Seventy-nine patients were included in the study, of
      whom 54 (68%) had an established diagnosis of Crohn's disease (CD). Median time
      from presentation to anti-TNF therapy was 204 days (174 vs 365 days for existing
      and new diagnosis of CD, respectively; P = 0.019). The mean number of surgical
      outpatient attendances, operations and MRI scans per patient was 1.03, 1.71 and
      1.03, respectively. Patients attended a mean of 1.49 medical clinics. Seton
      insertion was the most common procedure, accounting for 48.6% of all operations.
      Where care episodes ('clinical events per 30 days') were infrequent this
      correlated with prolongation of the pathway (r = -0.87; P < 0.01). CONCLUSION:
      This study highlights two key challenges in the treatment pathway: (i) delays in
      diagnosis of underlying CD in patients with anal fistula and (ii) the pathway to
      anti-TNF therapy is long, suggesting issues with service design and delivery.
      These should be addressed to improve patient experience and outcome.

PMID- 29569420
TI  - Impact of postgraduate education on advanced practice nurse activity - a national
      survey.
AB  - BACKGROUND: There is a wealth of international evidence concerning the
      contribution post-registration master's level education makes to advancing the
      discipline of nursing. There are approximately 277 nurse practitioners registered
      in NZ, but they account for only a small portion of nurses who have undertaken
      master's level education. The additional contribution these nurses make to the
      work environment through advanced practice activities has not, hitherto, been
      documented. OBJECTIVES: To report the extent of advanced practice nurse activity
      associated with various levels of nursing education in a sample of nurses working
      in clinical practice in New Zealand. METHOD: A replication of recent Australian
      research was done via a national cross-sectional survey of 3255 registered nurses
      and nurse practitioners in New Zealand using an online questionnaire to collect
      responses to the amended Advanced Practice Delineation survey tool. In addition,
      demographic data were collected including position titles and levels of
      postgraduate education. RESULTS: A positive association was found between
      postgraduate education at any level and more time spent in advanced practice
      activities. Independent of level of postgraduate education, the role a nurse
      holds also effects the extent of involvement in advanced practice activities.
      CONCLUSIONS: There is an additional contribution made to the work environment by
      nurses with master's level education which occurs even when they are not employed
      in an advanced practice role. IMPLICATIONS FOR NURSING POLICY: These findings are
      of significance to workforce policy and planning across the globe as countries
      work to sustain health services by increasing nursing capacity effectively within
      available resources.

PMID- 29569421
TI  - Periodic microstructures on bioactive glass surfaces enhance osteogenic
      differentiation of human mesenchymal stromal cells and promote osteoclastogenesis
      in vitro.
AB  - Bioactive glasses (BG) are known for their ability to bond to hard and soft
      tissues. We hypothesized that the stimulation of bone remodeling, including
      cellular bone forming and bone resorbing processes, can be increased by applying
      periodic microstructures on the glass surfaces in vitro. To test our hypothesis,
      two different BG (45S5 and 13-93) were microstructured in a groove-and-ridge
      pattern of different sizes by a novel casting process and tested in cell culture
      experiments using human mesenchymal stromal cells (hMSCs) and RAW 264.7 cells.
      The microstructures induced contact guidance of hMSCs and increased osteogenic
      marker gene expression of the stem cells, compared to non-structured glass
      surfaces as verified by ELISA and quantitative real-time PCR (qPCR) analyses.
      Furthermore, the structures stimulated the differentiation of RAW cells to
      osteoclast-like cells confirmed by TRAP gene expression and their resorption
      activity causing visible resorption lacunae. Our results demonstrate that
      periodically microstructured BG (especially 45S5) might improve the osteogenic
      differentiation of hMSCs and influence the activity of material resorbing cells
      in vitro. Hence, microstructuring of BG could enhance the remodeling process of
      bone substitutes critical for the formation of new bone tissue in vivo and thus
      be used to trigger bone remodeling kinetics in vivo. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1965-1978, 2018.

PMID- 29569422
TI  - Left ventricular remodelling and vascular adaptive changes in adolescents with
      obesity.
AB  - BACKGROUND: The aim of this study was to determine the effects of obesity on
      myocardial mechanics and ventriculo-arterial coupling (V-A) in children. METHODS:
      Strain parameters, stroke volume, arterial elastance, left ventricular (LV)
      elastance and V-A were compared after adjusting for age and hypertension and
      after multivariate sub-group analysis between patients with and without obesity.
      RESULTS: Among 123 retrospectively enrolled subjects, 6-21 years age, 79.7%
      males, 52% were obese. Median (range) Body Mass Index Z score was +2.35 (1.67
      4.43) for obese and +0.68 (-2.48-1.63) for non-obese. Subjects with obesity had
      higher LV mass indexed2.7 (LVMI2.7 ) compared with non-obese (P < 0.001). Lower
      global longitudinal strain (GLS) (P = 0.012), global circumferential strain (GCS)
      (P = 0.004), average longitudinal strain rate (P = 0.002) and average
      circumferential strain rate (P < 0.001) were seen in subjects with obesity; no
      difference was noted in arterial elastance, LV end systolic elastance and V-A.
      Increased LVMI2.7 , decreased GLS, GCS, average longitudinal strain rate, average
      circumferential strain rate and maintained V-A were noted in the multivariate
      analysis between subgroups. CONCLUSIONS: Obesity causes alterations in myocardial
      mechanics with preserved V-A in children. These findings may aid intervention in
      preventing the long-term cadiovascular effects of obesity.

PMID- 29569423
TI  - The Roles of Social Support and Health Literacy in Self-Management Among Patients
      With Chronic Kidney Disease.
AB  - AIMS: To investigate the relationships among social support, health literacy, and
      self-management, and the factors influencing self-management of chronic kidney
      disease (CKD). DESIGN: Cross-sectional study. METHODS: A random sample of 410
      patients was recruited from nephrology clinics. Data were collected using
      structured questionnaires and chart reviews from January 2013 to February 2014.
      Hierarchical regression analysis was used to determine the predictive factors of
      self-management behaviors and ?R2 to determine each variable's explanatory power.
      FINDINGS: Health literacy and social support were positively correlated with self
      management behaviors. Furthermore, social support, health literacy, and marital
      status were significant predictors of self-management behaviors. Social support
      had a relatively greater explanatory power for self-management behaviors than did
      health literacy. Particularly, healthcare provider support had the greatest
      influence on patients' self-management behaviors. CONCLUSIONS: Health literacy
      and social support play independent positive roles in self-management behaviors
      of patients with CKD, with social support having a particularly dominant role.
      Further research using a systems approach to improving self-management behaviors
      is necessary to clarify the role of social support. CLINICAL RELEVANCE: Health
      literacy and social support are independently and positively related to self
      management. Social support, which is a system-level factor, is a relatively
      stronger and crucial predictor than is health literacy. Nurses have to refine
      self-management programs to focus on families and adopt a systems approach to
      help CKD patients improve their self-management behaviors.

PMID- 29569424
TI  - Left atrial volume in patients with HER2-positive breast cancer: One step further
      to predict trastuzumab-related cardiotoxicity.
AB  - BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left
      ventricular (LV) ejection fraction (LVEF) because it can be potentially
      cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find
      other variables to predict cardiac dysfunction early. Left atrium (LA)
      enlargement has proven to be a powerful predictor of adverse outcomes in several
      disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ
      related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving
      TZ and undergoing transthoracic echocardiography at baseline and at follow-up
      every 3 months were retrospectively recruited. One-hundred sixty-two patients
      formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients
      (8.6%). Mean follow-up was 14 +/- 4 months. Cardiotoxicity occurred in 24
      patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction
      in a clinical model, after adjustment for age and hypertension (odds ratio per 5
      mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in
      a hemodynamic model, including ventricular sizes and systolic blood pressure
      level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01
      1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased
      progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation
      emerges as a condition associated with the development of cardiotoxicity in HER2
      positive breast cancer patients treated with TZ.

PMID- 29569425
TI  - Comparative analysis of nanobody sequence and structure data.
AB  - Nanobodies are a class of antigen-binding protein derived from camelids that
      achieve comparable binding affinities and specificities to classical antibodies,
      despite comprising only a single 15 kDa variable domain. Their reduced size makes
      them an exciting target molecule with which we can explore the molecular code
      that underpins binding specificity-how is such high specificity achieved? Here,
      we use a novel dataset of 90 nonredundant, protein-binding nanobodies with
      antigen-bound crystal structures to address this question. To provide a baseline
      for comparison we construct an analogous set of classical antibodies, allowing us
      to probe how nanobodies achieve high specificity binding with a dramatically
      reduced sequence space. Our analysis reveals that nanobodies do not diversify
      their framework region to compensate for the loss of the VL domain. In addition
      to the previously reported increase in H3 loop length, we find that nanobodies
      create diversity by drawing their paratope regions from a significantly larger
      set of aligned sequence positions, and by exhibiting greater structural variation
      in their H1 and H2 loops.

PMID- 29569426
TI  - Changes in thiol/disulfide homeostasis in juvenile idiopathic arthritis.
AB  - BACKGROUND: The pathogenesis of juvenile idiopathic arthritis (JIA) remains
      unknown, but imbalance between the oxidant and antioxidant defense systems may
      play a role. Measuring thiols in plasma provides an indirect indication of
      antioxidative defense. The aim of the present study was to investigate the
      association between JIA and dynamic thiol/disulfide homeostatic status. METHODS:
      This case-control study involved 34 JIA patients and 30 age- and gender-matched
      healthy controls. The patients were divided into subgroups according to
      Simplified Disease Activity Index (SDAI) score: active, SDAI > 3.3; remission,
      SDAI <= 3.3. RESULTS: Native thiol and total thiol were significantly lower in
      the JIA group than in the control group (P = 0.001). There was no significant
      difference in the disulfide/native thiol, disulfide/total thiol, and native
      thiol/total thiol ratios between the JIA and control groups (P > 0.05). Based on
      SDAI score, 22 JIA patients were in the remission subgroup, and 12 JIA patients
      were in the active subgroup. Native thiol and total thiol were significantly
      lower in the active JIA subgroup than in the remission subgroup (P = 0.001), but
      there were no significant differences in the other parameters. There was no
      significant difference in thiol and disulfide levels between systemic-onset JIA
      and other JIA (P > 0.05). CONCLUSIONS: Plasma thiol is lower in JIA patients,
      especially during periods of active disease, than in healthy controls, indicating
      that low thiol might be an important factor in the etiology of JIA and that
      antioxidant systems are negatively affected by inflammatory diseases, especially
      during periods of active disease.

PMID- 29569427
TI  - Sodium-glucose co-transporter-2 inhibitors and the risk of ketoacidosis in
      patients with type 2 diabetes mellitus: A nationwide population-based cohort
      study.
AB  - AIMS: To estimate the risk of diabetic ketoacidosis (DKA) associated with sodium
      glucose co-transporter-2 (SGLT2) inhibitor treatment compared with the risk
      associated with dipeptidyl-peptidase-4 (DPP-4) inhibitor treatment. METHODS: A
      nationwide population-based cohort study using claims data from the Korean Health
      Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was
      performed. A total of 56 325 patients who were started on SGLT2 inhibitors were
      included in this study and were matched with same number of patients who were
      started on DPP-4 inhibitors using propensity score matching. Kaplan-Meier curves
      and Cox proportional hazards regression analyses were used to estimate the risk
      of hospitalization for DKA. RESULTS: The risk of hospitalization for DKA was not
      increased in SGLT2 inhibitor users vs DPP-4 inhibitor users (hazard ratio [HR]
      0.956, 95% confidence interval [CI] 0.581-1.572; P = .996). The incidence rate of
      hospitalization for DKA during the first 30 days after initiation of the SGLT2
      inhibitor was 2.501 cases per 1000 person-years, which was higher than the rate
      during 3 years (0.614 cases per 1000 person-years). SGLT2 inhibitor use was
      associated with a higher HR in patients with diabetic microvascular complications
      (HR 2.044, 95% CI 0.900-4.640; P = .088) and in patients taking diuretics (HR
      3.648, 95% CI 0.720-18.480; P = .118), although these associations were not
      statistically significant. CONCLUSION: We found that SGLT2 inhibitor treatment
      did not increase the risk of DKA compared with DPP-4 inhibitor treatment. Our
      findings suggest that patients prescribed diuretics or those with microvascular
      complications may have a greater tendency to be hospitalized for DKA.

PMID- 29569428
TI  - Novel assay demonstrates that coronary artery disease patients have heightened
      procoagulant platelet response.
AB  - : Essentials Procoagulant platelets can be detected using GSAO in human whole
      blood. Stable coronary artery disease is associated with a heightened
      procoagulant platelet response. Agonist-induced procoagulant platelet response is
      not inhibited by aspirin alone. Collagen plus thrombin induced procoagulant
      platelet response is partially resistant to clopidogrel. SUMMARY: Background
      Procoagulant platelets are a subset of highly activated platelets with a critical
      role in thrombin generation. Evaluation of their clinical utility in thrombotic
      disorders, such as coronary artery disease (CAD), has been thwarted by the lack
      of a sensitive and specific whole blood assay. Objectives We developed a novel
      assay, utilizing the cell death marker, GSAO [(4-(N-(S
      glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation
      marker, P-selectin, to identify procoagulant platelets in whole blood by flow
      cytometry. Patients/Methods Using this assay, we characterized the procoagulant
      platelet population in healthy controls and a cohort of patients undergoing
      elective coronary angiography. Results In patients with CAD, compared with
      patients without CAD, there was a heightened procoagulant platelet response to
      thrombin (25.2% vs. 12.2%), adenosine diphosphate (ADP) (7.8% vs. 2.7%) and
      thrombin plus collagen (27.2% vs. 18.3%). The heightened procoagulant platelet
      potential in CAD patients was not associated with other markers of platelet
      function, including aggregation, dense granule release and activation of alpha2b
      beta3 integrin. Although dual antiplatelet therapy (DAPT) was associated with
      partial suppression of procoagulant platelets, this inhibitory effect on a
      patient level could not be predicted by aggregation response to ADP and was not
      fully suppressed by clopidogrel. Conclusions We report for the first time that
      procoagulant platelets can be efficiently detected in a few microliters of whole
      blood using the cell death marker, GSAO, and the platelet activation marker, P
      selectin. A heightened procoagulant platelet response may provide insight into
      the thrombotic risk of CAD and help identify a novel target for antiplatelet
      therapies in CAD.

PMID- 29569429
TI  - Recommended composition of influenza virus vaccines for use in the 2018-2019
      northern hemisphere influenza season.

PMID- 29569430
TI  - Antigenic and genetic characteristics of zoonotic influenza viruses and
      development of candidate vaccine viruses for pandemic preparedness.

PMID- 29569431
TI  - Polydopamine-Derivated Hierarchical Nanoplatforms for Efficient Dual-Modal
      Imaging-Guided Combination in Vivo Cancer Therapy.
AB  - Exploring multifunctional nanomaterials from biocompatible constituents, with
      integrated imaging and targeted combination therapeutic modalities of tumors in
      vivo, provides great prospects for clinical cancer theranostic applications.
      Here, we report a combination strategy for functionalization of polydopamine
      (PDA) nanohosts with magnetic response and stimuli-controlled drug release
      capabilities for in vivo cancer theranostic. The high processability of PDA as
      nanotemplates and surface coating layers as well as its natural affinity to
      metals facilitated the sandwich of a compact iron oxide nanoparticle layer into
      the PDA matrix, realizing enhanced near-infrared (NIR) photothermal conversion
      and strong superparamagnetic responsiveness. Additionally, the high reactivity of
      the PDA surface allowed facile linkage with reduction-responsive prodrugs and
      polyethylene glycol chains for in vivo chemotherapy of cancer. Under the magnetic
      resonance imaging/photoacoustic imaging dual-modal tumor imaging and active
      magnetic tumor targeting of the nanoagents in vivo, the effective tumor
      eradication was achieved via synergetic NIR photothermal ablation and anticancer
      drug delivery.

PMID- 29569432
TI  - Manipulation of Structural Colors in Liquid-Crystal Helical Structures Deformed
      by Surface Controls.
AB  - Structural colors from cholesteric liquid crystals (CLCs) are manipulated by
      changing the only surface anchoring energy of an alignment layer. This behavior
      comes from the fact that weak surface energy of the perfluoropolymer induces the
      tilting of the cholesteric helix. Such deformed CLC structures with durability
      are successfully demonstrated without any external field applications and
      additional solidification processes. In addition, electrical tunings of
      structural colors from the deformed CLCs occur at very low operating voltages,
      compared to those of conventional CLC structures. On the basis of easy and simple
      fabrication, high durability, electrical tunability at low operating voltages,
      and the unique optical characteristics, the new deformed CLC structure could lead
      to extension in applications of CLCs, including multifunctional sensors,
      displays, and lasers.

PMID- 29569433
TI  - Pronounced Side Chain Effects in Triple Bond-Conjugated Polymers Containing
      Naphthalene Diimides for n-Channel Organic Field-Effect Transistors.
AB  - Three triple bond-conjugated naphthalene diimide (NDI) copolymers, poly{[ N, N'
      bis(2-R1)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]- alt-[(2,5-bis(2-R2)
      1,4-phenylene)bis(ethyn-2,1-diyl)]} (PNDIR1-R2), were synthesized via Sonogashira
      coupling polymerization with varying alkyl side chains at the nitrogen atoms of
      the imide ring and 2,5-positions of the 1,4-diethynylbenzene moiety. Considering
      their identical polymer backbone structures, the side chains were found to have a
      strong influence on the surface morphology/nanostructure, thus playing a critical
      role in charge-transporting properties of the three NDI-based copolymers. Among
      the polymers, the one with an octyldodecyl (OD) chain at the nitrogen atoms of
      imide ring and a hexadecyloxy (HO) chain at the 2,5-positions of 1,4
      diethynylbenzene, P(NDIOD-HO), exhibited the highest electron mobility of 0.016
      cm2 V-1 s-1, as compared to NDI-based copolymers with an ethylhexyl chain at the
      2,5-positions of 1,4-diethynylbenzene. The enhanced charge mobility in the
      P(NDIOD-HO) layers is attributed to the well-aligned nano-fiber-like surface
      morphology and highly ordered packing structure with a dominant edge-on
      orientation, thus enabling efficient in-plane charge transport. Our results on
      the molecular structure-charge transport property relationship in these materials
      may provide an insight into novel design of n-type conjugated polymers for
      applications in the organic electronics of the future.

PMID- 29569434
TI  - Visual and Colorimetric High-Throughput Analysis of Chiral Carboxylic Acids Based
      on Enantioselective Charge Shielding of Gold Nanoparticles.
AB  - Because chiral carboxylic acids (CCAs) are a class of important biological
      molecules and common functional moieties found in pharmaceutical molecules, the
      chiral analysis of CCAs has received much attention. Herein, we developed a
      simple, rapid, and cost-effective method for visual and colorimetric high
      throughput analysis of CCAs using chiral di-imine structure-modified gold
      nanoparticles (C-AuNPs) as the probe. The C-AuNPs are positively charged in the
      presence of zinc ion, and they can be enantioselectively shielded by the
      negatively charged CCA enantiomers. Therefore, upon the addition of different
      concentrations and enantiomeric excess (ee) of CCAs, the C-AuNP-based sensor
      shows the different levels of aggregation along with the visual changes in
      solution color, which can achieve simultaneous analysis of the concentration and
      ee of CCAs. The chiral recognition mechanism based on C-AuNPs was investigated by
      the determination of binding constants ( K) and molecular simulation methods. Our
      approach is expected to have the wide-ranging applications in the developing
      region for enantio-sensing of various chiral drugs and biomolecules.

PMID- 29569435
TI  - Overcoming Multidrug Resistance through the GLUT1-Mediated and Enzyme-Triggered
      Mitochondrial Targeting Conjugate with Redox-Sensitive Paclitaxel Release.
AB  - Multidrug resistance (MDR) is thought to be the major obstacle leading to the
      failure of paclitaxel (PTX) chemotherapy. To solve this problem, a glucose
      transporter-mediated and matrix metalloproteinase 2 (MMP2)-triggered
      mitochondrion-targeting conjugate [glucose-polyethylene glycol (PEG)-peptide
      triphenylphosponium-polyamidoamine (PAMAM)-PTX] composed of a PAMAM dendrimer and
      enzymatic detachable glucose-PEG was constructed for mitochondrial delivery of
      PTX. The conjugate was characterized by a 30 nm sphere particle, MMP2-sensitive
      PEG outer layer detachment from PAMAM, and glutathione (GSH)-sensitive PTX
      release. It showed higher cellular uptake both in glucose transporter 1 (GLUT1)
      overexpressing MCF-7/MDR monolayer cell (2D) and multicellular tumor spheroids
      (3D). The subcellular location study showed that it could specifically accumulate
      in the mitochondria. Moreover, it exhibited higher cytotoxicity against MCF-7/MDR
      cells, which significantly reverse the MDR of MCF-7/MDR cells. The MDR reverse
      might be caused by reducing the ATP content through destroying the mitochondrial
      membrane as well as by down-regulating P-gp expression. In vivo imaging and
      tissue distribution indicated more conjugate accumulated in the tumor of the
      tumor-bearing mice model. Consequently, the conjugate showed better tumor
      inhibition rate and lower body weight loss, which demonstrated that it possessed
      high efficiency and low toxicity. This study provides glucose-mediated GLUT
      targeting, MMP2-responsive PEG detachment, triphenylphosponium-mediated
      mitochondria targeting, and a GSH-sensitive intracellular drug release conjugate
      that has the potential to be exploited for overcoming MDR of PTX.

PMID- 29569436
TI  - Macro-SICM: A Scanning Ion Conductance Microscope for Large-Range Imaging.
AB  - The scanning ion conductance microscope (SICM) is a versatile, high-resolution
      imaging technique that uses an electrolyte-filled nanopipet as a probe. Its
      noncontact imaging principle makes the SICM uniquely suited for the investigation
      of soft and delicate surface structures in a liquid environment. The SICM has
      found an ever-increasing number of applications in chemistry, physics, and
      biology. However, a drawback of conventional SICMs is their relatively small scan
      range (typically 100 MUm * 100 MUm in the lateral and 10 MUm in the vertical
      direction). We have developed a Macro-SICM with an exceedingly large scan range
      of 25 mm * 25 mm in the lateral and 0.25 mm in the vertical direction. We
      demonstrate the high versatility of the Macro-SICM by imaging at different length
      scales: from centimeters (fingerprint, coin) to millimeters (bovine tongue
      tissue, insect wing) to micrometers (cellular extensions). We applied the Macro
      SICM to the study of collective cell migration in epithelial wound healing.

PMID- 29569437
TI  - Quantitative Profiling of Protein Carbonylations in Ferroptosis by an Aniline
      Derived Probe.
AB  - Ferroptosis is a regulated form of necrotic cell death implicated in
      carcinogenesis and neurodegeneration that is driven by phospholipid peroxidation.
      Lipid-derived electrophiles (LDEs) generated during this process can covalently
      modify proteins ("carbonylation") and affect their functions. Here we report the
      development of a quantitative chemoproteomic method to profile carbonylations in
      ferroptosis by an aniline-derived probe. Using the method, we established a
      global portrait of protein carbonylations in ferroptosis with >400 endogenously
      modified proteins and for the first time, identified >20 residue sites with
      endogenous LDE modifications in ferroptotic cells. Specifically, we discovered
      and validated a novel cysteine site of modification on voltage-dependent anion
      selective channel protein 2 (VDAC2) that might play an important role in
      sensitizing LDE signals and mediating ferroptosis. Our results will contribute to
      the understanding of ferroptotic signaling and pathogenesis and provide potential
      biomarkers for ferroptosis detection.

PMID- 29569438
TI  - Tunable Plasmonic Cavity for Label-free Detection of Small Molecules.
AB  - Owing to its high sensitivity and high selectivity along with rapid response
      time, plasmonic detection has gained considerable interest in a wide variety of
      sensing applications. To improve the fieldwork applicability and reliability of
      plasmonic detection, the integration of plasmonic nanoparticles into optical
      devices is desirable. Herein, we propose an integrated label-free detection
      platform comprising a plasmonic cavity that allows sensitive molecular detection
      via either surface-enhanced Raman scattering (SERS) or plasmon resonance energy
      transfer (PRET). A small droplet of metal ion solution spontaneously produces a
      plasmonic cavity on the surface of uncured poly(dimethylsiloxane) (PDMS), and as
      PDMS is cured, the metal ions are reduced to form a plasmonic antennae array on
      the cavity surface. Unique spherical feature and the integrated metallic
      nanoparticles of the cavity provide excellent optical functions to focus the
      incident light in the cavity and to rescatter the light absorbed by the
      nanoparticles. The optical properties of the plasmonic cavity for SERS or PRET
      are optimized by controlling the composition, size, and density of the metal
      nanoparticles. By using the cavity, we accomplish both 1000-fold sensitive
      detection and real-time monitoring of reactive oxygen species secreted by live
      cells via PRET. In addition, we achieve sensitive detection of trace amounts of
      toxic environmental molecules such as 5-chloro-2-methyl-4-isothiazolin-3-one/2
      methyl-4-isothiazol-3-one (CMIT/MIT) and bisphenol A, as well as several small
      biomolecules such as glucose, adenine, and tryptophan, via SERS.

PMID- 29569439
TI  - Critical Role of Vertical Phase Separation in Small-Molecule Organic Solar Cells.
AB  - An inverted device structure is a more stable configuration than a regular device
      structure for solution-processed organic solar cells (OSCs). However, most of the
      solution-processed small-molecule OSCs (SM-OSCs) reported in the literature used
      the regular device structure, and a regular device normally exhibits a higher
      efficiency than an inverted device. Herein, a representative small-molecule
      DR3TBDTT was selected to figure out the reason for photovoltaic performance
      differences between regular and inverted devices. The mechanisms for a reduced
      open-circuit voltage ( Voc) and fill factor (FF) in the inverted device were
      studied. The reduced Voc and FF is due to the vertical phase separation with
      excess [6,6]-phenyl-C71-butyric acid methyl ester near the air/blend surface,
      which leads to a reduction in build-in voltage and unbalanced charge transport in
      the inverted device. Another reason for the reduced FF is the unfavorable
      DR3TBDTT crystallite orientation distribution along the film thickness, which is
      preferential edge-on crystallites in the top layer of the blend film and the
      increased population of face-on crystallites in the bottom layer of the blend
      film. This study illustrates that the morphology plays a key role in photovoltaic
      performance difference between regular and inverted devices and provides useful
      guidelines for further optimization of the morphology of solution-processed SM
      OSCs.

PMID- 29569440
TI  - Transparent Polymeric Films Capable of Healing Millimeter-Scale Cuts.
AB  - Transparent polymeric films have been successfully integrated with self-healing
      capabilities. However, these films can only heal damages in the scale of several
      to several tens of micrometers, thereby greatly limiting their practical
      applications. The present study reports the fabrication of transparent polymeric
      films capable of healing millimeter-scale cuts by incorporating hydrogen-bonding
      units into zwitterionic polymer films, which are cross-linked by electrostatic
      interactions. The intermolecular interactions in the resulting films are greatly
      reduced when the films absorb water as a result of the reversibility of hydrogen
      bonding and electrostatic interactions, thereby promoting the flowability of the
      film materials. Thus, the transparent films can heal 7.9 mm wide cuts and recover
      their damaged transparency following exposure to water. Furthermore, owing to
      their strong binding affinity to water molecules, the healable transparent films
      can effectively clean up oil fouled on dry films following rinsing with water.
      The combination of hydrogen bonding and electrostatic interactions provides a new
      means of design for transparent films with enhanced healing capabilities and an
      extended service life.

PMID- 29569442
TI  - Brominated Flame Retardants and Organophosphate Esters in Preschool Dust and
      Children's Hand Wipes.
AB  - Children spend a considerable part of their day in preschool, where they may be
      exposed to hazardous chemicals in indoor dust. In this study, brominated flame
      retardants (BFRs) and organophosphate esters (OPEs) were analyzed in preschool
      dust ( n = 100) and children's hand wipe samples ( n = 100), and diphenyl
      phosphate (DPHP) was analyzed in urine ( n = 113). Here we assessed children's
      exposure via dust, identified predictors for chemicals in dust, and studied
      correlations between different exposure measures. The most abundant BFRs in dust
      were decabromodiphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) found
      at median levels of 270 and 110 ng/g dust, respectively. Tris(2-butoxyethyl)
      phosphate (TBOEP) was the most abundant OPE, found at a median level of 79 000
      ng/g dust. For all OPEs and some BFRs, there were significant correlations
      between the levels in dust and hand wipes. In addition, triphenyl phosphate
      (TPHP) in preschool dust was significantly correlated with the corresponding
      metabolite DPHP in children's urine. The levels of pentaBDEs in dust were higher
      in older preschools compared with newer, whereas levels of DBDPE were higher in
      newer preschools. Children's estimated intakes of individual BFRs and OPEs via
      preschool dust were below available health-based reference values. However, there
      are uncertainties about the potential health effects of some emerging BFRs and
      OPEs.

PMID- 29569441
TI  - Reentrant Phase Transitions and Non-Equilibrium Dynamics in Membraneless
      Organelles.
AB  - Compartmentalization of biochemical components, interactions, and reactions is
      critical for the function of cells. While intracellular partitioning of molecules
      via membranes has been extensively studied, there has been an expanding focus in
      recent years on the critical cellular roles and biophysical mechanisms of action
      of membraneless organelles (MLOs) such as the nucleolus. In this context, a
      substantial body of recent work has demonstrated that liquid-liquid phase
      separation plays a key role in MLO formation. However, less is known about MLO
      dissociation, with phosphorylation being the primary mechanism demonstrated thus
      far. In this Perspective, we focus on another mechanism for MLO dissociation that
      has been described in recent work, namely a reentrant phase transition (RPT).
      This concept, which emerges from the polymer physics field, provides a
      mechanistic basis for both formation and dissolution of MLOs by monotonic tuning
      of RNA concentration, which is an outcome of cellular processes such as
      transcription. Furthermore, the RPT model also predicts the formation of dynamic
      substructures (vacuoles) of the kind that have been observed in cellular MLOs. We
      end with a discussion of future directions in terms of open questions and methods
      that can be used to answer them, including further exploration of RPTs in vitro,
      in cells, and in vivo using ensemble and single-molecule methods as well as
      theory and computation. We anticipate that continued studies will further
      illuminate the important roles of reentrant phase transitions and associated non
      equilibrium dynamics in the spatial patterning of the biochemistry and biology of
      the cell.

PMID- 29569443
TI  - Near-Infrared-Emitting CuInS2/ZnS Dot-in-Rod Colloidal Heteronanorods by Seeded
      Growth.
AB  - Synthesis protocols for anisotropic CuInX2 (X = S, Se, Te)-based
      heteronanocrystals (HNCs) are scarce due to the difficulty in balancing the
      reactivities of multiple precursors and the high solid-state diffusion rates of
      the cations involved in the CuInX2 lattice. In this work, we report a multistep
      seeded growth synthesis protocol that yields colloidal wurtzite CuInS2/ZnS dot
      core/rod shell HNCs with photoluminescence in the NIR (~800 nm). The wurtzite
      CuInS2 NCs used as seeds are obtained by topotactic partial Cu+ for In3+ cation
      exchange in template Cu2- xS NCs. The seed NCs are injected in a hot solution of
      zinc oleate and hexadecylamine in octadecene, 20 s after the injection of sulfur
      in octadecene. This results in heteroepitaxial growth of wurtzite ZnS primarily
      on the Sulfur-terminated polar facet of the CuInS2 seed NCs, the other facets
      being overcoated only by a thin (~1 monolayer) shell. The fast (~21 nm/min)
      asymmetric axial growth of the nanorod proceeds by addition of [ZnS] monomer
      units, so that the polarity of the terminal (002) facet is preserved throughout
      the growth. The delayed injection of the CuInS2 seed NCs is crucial to allow the
      concentration of [ZnS] monomers to build up, thereby maximizing the anisotropic
      heteroepitaxial growth rates while minimizing the rates of competing processes
      (etching, cation exchange, alloying). Nevertheless, a mild etching still
      occurred, likely prior to the onset of heteroepitaxial overgrowth, shrinking the
      core size from 5.5 to ~4 nm. The insights provided by this work open up new
      possibilities in designing multifunctional Cu-chalcogenide based colloidal
      heteronanocrystals.

PMID- 29569444
TI  - Photoredox-Catalyzed Trifluoromethylative Intramolecular Cyclization: Synthesis
      of CF3-Containing Heterocyclic Compounds.
AB  - A general photoredox-catalyzed intramolecular cyclization was developed for the
      synthesis of trifluoromethylated heterocyclic compounds. The reaction proceeded
      smoothly under mild photocatalytic conditions with high functional group
      tolerance, allowing the preparation of oxygen-, sulfur-, or nitrogen-containing
      heterocycles of different sizes. The broad substrate scope demonstrated the
      complexity-building potential of the strategy.

PMID- 29569445
TI  - Adversarial Threshold Neural Computer for Molecular de Novo Design.
AB  - In this article, we propose the deep neural network Adversarial Threshold Neural
      Computer (ATNC). The ATNC model is intended for the de novo design of novel small
      molecule organic structures. The model is based on generative adversarial network
      architecture and reinforcement learning. ATNC uses a Differentiable Neural
      Computer as a generator and has a new specific block, called adversarial
      threshold (AT). AT acts as a filter between the agent (generator) and the
      environment (discriminator + objective reward functions). Furthermore, to
      generate more diverse molecules we introduce a new objective reward function
      named Internal Diversity Clustering (IDC). In this work, ATNC is tested and
      compared with the ORGANIC model. Both models were trained on the SMILES string
      representation of the molecules, using four objective functions (internal
      similarity, Muegge druglikeness filter, presence or absence of sp3-rich
      fragments, and IDC). The SMILES representations of 15K druglike molecules from
      the ChemDiv collection were used as a training data set. For the different
      functions, ATNC outperforms ORGANIC. Combined with the IDC, ATNC generates 72% of
      valid and 77% of unique SMILES strings, while ORGANIC generates only 7% of valid
      and 86% of unique SMILES strings. For each set of molecules generated by ATNC and
      ORGANIC, we analyzed distributions of four molecular descriptors (number of
      atoms, molecular weight, logP, and tpsa) and calculated five chemical statistical
      features (internal diversity, number of unique heterocycles, number of clusters,
      number of singletons, and number of compounds that have not been passed through
      medicinal chemistry filters). Analysis of key molecular descriptors and chemical
      statistical features demonstrated that the molecules generated by ATNC elicited
      better druglikeness properties. We also performed in vitro validation of the
      molecules generated by ATNC; results indicated that ATNC is an effective method
      for producing hit compounds.

PMID- 29569446
TI  - WHO: healthy diet to prevent chronic diseases and caries.
AB  - For some years now, the WHO has recommended less than 10% of energy intake from
      free sugars. The same document also stresses the need to bring this limit below
      5% as soon as possible. These guidelines have been promoted with the aim of
      reducing the prevalence of chronic non-communicable diseases such as diabetes,
      cardiovascular disease, obesity and metabolic syndrome. At the same time, the
      reduction of free sugars in the diet can be part of a strategy to reduce the
      prevalence of caries, which is known to be an infectious and transmissible
      multifactorial disease known to be "triggered" by wrong dietary habits. For this
      reason, paediatricians and paediatric dentists should combine their efforts to
      promote good eating habits from an early age and perhaps even earlier! In fact,
      we should teach future mothers and their children to prefer slowly absorbed
      sugars and drastically reduce the intake of free sugars with the diet. As soon as
      the child is able to chew, the diet should include fibre-rich foods, and water
      should be preferred over any sweetened drink. Raising children with a healthy and
      balanced diet means investing in his or her long-term general health and offer a
      dental future free of caries!

PMID- 29569447
TI  - Association between salivary cortisol level and caries in early childhood.
AB  - AIM: The present study aimed to evaluate the association between caries and oral
      health status, age, salivary cortisol levels, and parental education in children
      with and without prior dental caries experience. MATERIALS AND METHODS: An
      observational case-control study was performed including 122 children aged
      between 3 and 6 years who were clinically examined for caries experience using
      the sum of decayed, missing, and filled teeth in the primary (dmft index) and
      permanent (DMFT index) dentition. Oral health status was also evaluated using the
      Simplified Oral Hygiene index (OHI-S). Parents filled a questionnaire to provide
      information on other variables. Salivary cortisol levels were estimated 1 h after
      routine dental brushing. RESULTS: We found that dental caries experience was
      associated with cortisol level, plaque, age, and high calculus levels. High
      cortisol levels and age are important risk factors for caries development with
      odds ratios of 3.05 (95% CI: 1.84-5.06) and 1.59 (95% CI: 1.09-2.58),
      respectively. Multivariate logistic analysis showed that cortisol level and age
      were independently associated with caries presence. Caries experience was not
      associated with education of parents, feeding-hygiene habits of child or birth
      events. CONCLUSION: The present findings support the hypothesis that caries is
      mainly correlated with high salivary cortisol levels. Dental caries experience in
      children was also positively associated with tartar, plaque, and age.

PMID- 29569448
TI  - Apical extrusion of debris in primary molar root canals using mechanical and
      manual systems.
AB  - AIM: Apical extrusion of debris in primary root canal treatment has not been well
      elucidated. The purpose of this study is to compare the amount of apically
      extruded debris during the preparation of primary molar root canals using
      ProTaper, ProTaper Next, Self-adjusting File (SAF) and hand files. MATERIALS AND
      METHODS: One hundred sixty extracted primary mandibular molar teeth were assigned
      to 2 groups: Group 1: Resorbed (n=80) and Group 2: Non-resorbed (n=80) and
      randomly to four subgroups (n=20 teeth for each subgroup) according to the
      instruments used, ProTaper, ProTaper Next, SAF, and hand file. The apically
      extruded debris was collected and dried in preweighed Eppendof tubes. The dry
      weight was calculated by subtracting the preoperative weight from the
      postoperative weight. STATISTICS: Data were analysed statistically using the
      ANOVA and the Bonferroni post hoc t-test. RESULTS: The amount of apically
      extruded debris was significantly less for the non-resorbed group compared to the
      resorbed group (P<0.05). Regardless of the resorption groups, ProTaper Next and
      SAF extruded significantly less debris than did the ProTaper and hand files
      (P<0.05), while no statistically significant difference was found between
      ProTaper Next and SAF (P>0.05). CONCLUSION: All instruments caused apically
      extruded debris in primary teeth.

PMID- 29569449
TI  - Parental-caregiver perception of child oral-health related quality of life
      following zirconia crown placement and non-restoration of carious primary
      anterior teeth.
AB  - AIM: Dental caries in preschool children has shown significant impact on
      children's OHRQoL and family functioning. The aim of this study was to measure
      parents' perceptions of children's OHRQoL and impact of children's orofacial
      conditions on the family following management of carious anterior teeth with
      either zirconia crown placement or non-restorative therapy. MATERIALS AND
      METHODS: Parents of medically fit children aged from 2 years to 6 years attending
      specialist paediatric clinics were recruited and a questionnaire that included
      the Global Oral Health Rating Item, Parent-Caregivers Perception Questionnaire (P
      CPQ-8) and Family Impact Scale (FIS-8) was distributed at a recall visit 3-6
      months following treatment. Twenty patients were allocated in each of the two
      groups; zirconia crown and non-restorative therapy. RESULTS: The Global Oral
      Health Rating item scores were significantly different between groups (p=0.038).
      Children health effects due to dental status were more among patients treated
      with zirconia crowns. However, PCPQ and FIS total and individual scores were not
      significantly different between groups (p>0.05) except that children suffered
      more food impaction between teeth among patients treated with zirconia crowns
      (p=0.002). CONCLUSIONS: Parents' perceptions of children's OHRQoL and impact on
      family were similar when anterior carious teeth were managed with zirconia crown
      placement or non-restorative therapy.

PMID- 29569450
TI  - Maxillary tridimensional changes after slow expansion with leaf expander in a
      sample of growing patients: a pilot study.
AB  - AIM: The aim of this study is to evaluate the dento-alveolar effects of slow
      maxillary expansion using the Leaf Expander in a sample of growing patients with
      maxillary transverse deficiency, unilateral cross bite and mandibular shift.
      MATERIALS AND METHODS: The study included 10 patients, 3 male and 7 female (mean
      age 7.5 + 7 months), treated with Leaf Expander anchored on the upper deciduous
      teeth. Digital models were obtained by a lab scan of the pvs impressions at the
      beginning of the therapy (T1) and at the removal of the palatal expander (T2).
      Five parameters were measured: 1) the distance between the first upper permanent
      molars; 2) the distance between the upper second deciduous molars; 3) the
      distance between the upper canine cusps 4) the distance between the first lower
      permanent molars; 5) the distance of the lower canine cusps. RESULTS: In all
      patients complete correction of posterior crossbite was achieved on average in 4
      months, with a spontaneous expansion of the upper first permanent molars.
      Significant increases in the dento-alveolar transversal diameters were obtained.
      Increases were also observed in the anterior mandibular arch diameter (+ 1 mm).
      CONCLUSIONS: These findings suggest that slow maxillary expansion using Leaf
      Expander appliance could be a reasonable alternative to conventional maxillary
      expansion therapy in the early mixed dentition.

PMID- 29569451
TI  - A comparative assessment of changes in dental arches associated with different
      activation protocols of rapid maxillary expansion.
AB  - AIM: The aim of this study is to compare dental arch changes associated with
      different activation protocols of maxillary expander. MATERIALS AND METHODS: A
      sample of 101 subjects with constricted maxillary arches (49 males and 52
      females; mean age 10.96 +/- 1.91 years) was enrolled in the study. All subjects
      underwent RME with a stainless steel banded expander cemented to the maxillary
      first molars and the expansion screw was randomly activated with two different
      rapid maxillary expansion protocols (one- quarter per day or two quarters per
      day). The study also involved a control group of 22 subjects (10 females and 12
      males, mean age 10.39 +/- 1.32 years) who underwent no treatment. A statistical
      comparison between the dental arch measures obtained before and after treatment
      in the two groups was performed. RESULTS: The Wilcoxon rank-sum test shows
      statistically significant differences of the measurement increases between the
      two activation protocols (at least p=0.01). Statistically significant differences
      were also reported in comparison with the control group. CONCLUSIONS: A faster
      activation protocol could be able to determine a greater anterior opening of the
      mid-palatal suture. Moreover, it seems to yield a higher width increase in the
      molar area.

PMID- 29569452
TI  - Single tooth anaesthesia: a new approach to the paediatric patient. A clinical
      experimental study.
AB  - AIM: The objective of this study is to assess the efficacy of the STA Wand System
      with respect to pain and fear reduction in paediatric patients and by using the
      Single Tooth Anaesthesia (STA) technique. MATERIALS AND METHODS: Patients
      included children and teenagers between 6 and 17 years of age, who required the
      administration of local anaesthesia prior to expected treatments. Local
      anaesthesia was performed by means of the electronic STA Wand System (Milestone
      scientific., Inc.) adopting the Single Tooth Anaesthesia (STA) technique. Pre-
      and post-anaesthesia, the patients were asked to complete the Wong-Baker faces
      image scale and the provider filled in the Frankl Scale. RESULTS: All treatments
      were completed successfully and no collaboration issues were recorded. Frankl's
      assessment showed that 91% of patients regarded dental experience positively. The
      efficacy of the computer-assisted anaesthesia was at 100% when treating primary
      teeth, and 70% for procedures on permanent teeth. Almost the totality of treated
      patients (94%) gave a positive evaluation after having tried the device with STA
      technique. Only 6% of the patients assessed the procedure negatively.
      CONCLUSIONS: The STA technique allows for absence of anticipatory anxiety,
      absence of physical pain, no anaesthetic effects in the perioral tissues and a
      controllable, lower dosage of the anaesthetic liquid.

PMID- 29569453
TI  - The safety of paediatric dentistry procedures under general anaesthesia. A five
      year experience of a tertiary care center.
AB  - AIM: Frequently general anaesthesia (GA) is used to treat noncompliant children.
      Especially in children with morbid diseases general anaesthesia can be a
      challenging procedure for anaesthetists. The aim of this paper was to evaluate
      the risks and adverse reactions with a special focus on the impact of existing
      medication conditions and syndromes. MATERIALS AND METHODS: and methods Records
      of children up to 10 years of age, who were admitted for paediatric dentistry
      procedures under GA from January 2011 to December 2016 at the University Hospital
      of the University of Aachen (Germany), were reviewed. A special attention was
      paid to the intra- and perioperative critical adverse reactions and concomitant
      systemic conditions and their impact on treatment outcome. RESULTS: Two hundred
      and twenty patients were admitted for dental restorations. Critical adverse
      reactions occurred in 4% of the treated patients and they were statistically
      significantly (p=0.004) related to the ASA classification above II. The use of a
      laryngeal mask airway was significantly associated (p<0.001) with a shorter
      duration of surgery. Most common concomitant medical conditions were congenital
      heart disease, mental retardation and inherited syndromes. CONCLUSION: Although
      the administration of general anaesthesia in infants and children can be regarded
      as a safe procedure, clinically significant adverse reactions can occur,
      especially in patients with an existing medical condition.

PMID- 29569454
TI  - The possibility of modification and improvement of dental services in Poland for
      children and adolescents with special emphasis on orthodontic service.
AB  - AIM: World Dental Federation reveals that dental caries is one of the most common
      diseases in the world, and as much as 90% of the population is facing oral cavity
      problems. About 28% of teenagers aged 10 and 15 absolutely needs orthodontic
      treatment and about another third of this age group represents very serious
      cases. The aim of this study is to verify the authorial model which modifies and
      facilitates the system of dental services in Poland with a special emphasis on
      orthodontic service. MATERIAL AND METHODS: The research was carried out with the
      method of diagnostic survey through a survey questionnaire. For this study, 1159
      people were questioned for the research. In order to check the reliance between
      the variables Pearson chi-square test and the test of the Highest Reliability
      were used. Average market prices and the "prices expected" by the Greater Poland
      Voivodship Department of National Healthcare System were used to price dental
      services. RESULTS: The research revealed that the highest percentage of people
      who used only private dental services is between 19 and 64 years of age and the
      lowest percentage is represented by the elderly, i.e. subjects over 65 years of
      age. As for the dental services offered by the National Health Fund, the highest
      percentage of patients are children and adolescents under 18 and the lowest
      percentage of patients is represented by people in the working age. The tendency
      towards private healthcare is in direct proportion to parents' increase in the
      level of education. The main reason why parents take their children to a private
      dentist is the long waiting time for the visit offered by the National Health
      Fund as well as better materials and equipment offered by private dentists. The
      costs connected with extending the basket of guaranteed services for children and
      youngsters are combined with the increase in National Health Fund expenditure
      reaching EUR 7,014,151. The lack of refunding dental services for patients aged
      19-64 will generate savings reaching about EUR 34,756,765. CONCLUSION: The
      reduction of public funds allocated for dental treatment of patients aged 19-64
      will generate savings which will satisfy the needs connected with the increase in
      the range of refunded orthodontic treatment with the use of orthodontic permanent
      braces for patients under 18 years of age. The solution suggested will only
      slightly affect people in the working age as they reveal a strong tendency for
      treatment financed with their private funds.

PMID- 29569455
TI  - Laser labial frenectomy: a simplified and predictable technique. Retrospective
      clinical study.
AB  - AIM: Anomalous maxillary median labial frenum may be associated with undesired
      effects such as persistence of diastema between anterior teeth or traction of
      marginal gingiva. The aim of this study was to propose a surgical frenum
      repositioning technique that is minimally invasive, safe, easy, reproducible, and
      predictable. Another objective of the study was to identify clinical scenarios
      that could have indication for labial frenectomy associated with early
      orthodontic therapy, so as to justify early frenum repositioning in children. A
      retrospective assessment of clinical outcomes of this technique is described.
      MATERIALS AND METHODS: A total of 20 frenectomies were performed on children aged
      8 to 10 years. Frenectomies were performed with Er:YAG laser set at 150mJ 2.25
      3.0W and 15-20 pulse per second, with water spray. Recall visits were done at 7,
      21 and 90 days and 1, 2, 3 and 4 years. RESULTS: At post-operative visits, all
      patients reported no post-operative pain or minimal discomfort. None experienced
      post-operative bleeding at a distance of few hours. All patients reported that
      the procedure was well tolerated and "acceptable". No recurrences occurred 4
      years after frenectomy. CONCLUSION: The Er:YAG laser used in this study allowed
      considerable reduction of the operating time, reducing the amount of local
      anaesthetic used as well as avoiding surgical sutures. The surgical design and
      technique also minimised post-operative discomfort and complications resulting in
      stable healing overtime, making the procedure fully accepted by children.

PMID- 29569456
TI  - Is laser conditioning a valid alternative to conventional etching for aesthetic
      brackets?
AB  - AIM: ER:Yag lasers have been described as a more conservative alternative to
      conventional acid-etching enamel conditioning technique, when bonding
      conventional metallic orthodontic brackets. Since the use of aesthetic
      orthodontic brackets is constantly increasing, the purpose of the present report
      has been to test laser conditioning with different aesthetic brackets. MATERIALS
      AND METHODS: Study Design: Five different aesthetic brackets (microfilled
      copolymer, glass fiber, sapphire, polyoxymethylene and sintered ceramic) were
      tested for shear bond strength and Adhesive Remnant Index scores using two
      different enamel conditioning techniques (acid etching and ER:Yag laser
      application). Two hundred bovine incisors were extracted, cleaned and embedded in
      resin. Specimens were then divided into 10 groups with random tables. Half of the
      specimens were conditioned with conventional orthophosphoric acid gel, the other
      half with ER:Yag laser. Different aesthetic brackets (microfilled copolymer,
      glass fiber, sapphire, polyoxymethylene and sintered ceramic) were then bonded to
      the teeth. Subsequently all groups were tested in shear mode with a Universal
      Testing Machine. Shear bond strength values and adhesive remnant index scores
      were recorded. Statistical analysis was performed. RESULTS: When considering
      conventional acid etching technique, sapphire, polyoxymethylene and sintered
      ceramic brackets exhibited the highest SBS values. Lowest values were reported
      for microfilled copolymer and glass fiber appliances. A significant decrease in
      SBS values after laser conditioning was reported for sapphire, polyoxymethylene
      and sintered ceramic brackets, whereas no significant difference was reported for
      microfilled copolymer and glass fiber brackets. Significant differences in ARI
      scores were also reported. CONCLUSIONS: Laser etching can significantly reduce
      bonding efficacy of sapphire, polyoxymethylene and sintered ceramic brackets.

PMID- 29569457
TI  - Titanium TSME appliance for patients allergic to nickel.
AB  - AIM: The aim of this article is to describe the use of a titanium TSME appliance
      for patients with allergy to resin and nickel. We aim to highlight the optimal
      way to avoid problems such as stomatitis and peri-labial dermatitis, which
      generally appear in patients who use traditional orthodontic appliances made in
      acrylic resin and steel. MATERIALS AND METHODS: The construction of a titanium
      appliance is described and a case treated with it is reported. RESULTS: The
      titanium TSME presented in this paper has excellent biocompatibility due to its
      ability to form superficial oxides, which prevent oxidation and thus corrosion.
      CONCLUSION: The non-allergic properties of titanium allow to propose it as an
      alternative in patients with a long-term history of allergic reactions to nichel.

PMID- 29569458
TI  - Clinical, histomorphological and therapeutic features of the Van der Woude
      Syndrome: literature review and presentation of an unusual case.
AB  - BACKGROUND: Van der Woude syndrome (VWS), an autosomal dominant condition
      associated with lower lip pits and/or cleft palate, is caused by mutations in the
      interferon regulatory factor 6 gene (lRF6 gene). The genetic alterations
      identified to date that contribute to expression of the syndrome are chiefly
      mutations located on chromosome 1 (the largest of our chromosomes), mutations at
      p36 that codifies the gene GRHL (grainy-head transcriptor factor) and mutations
      involving IRF6 (interferon regulatory factor). With frequency ranging from
      1:35,000 to 1:100,000, depending on ethnicity, gender, and socio-economic status,
      the syndrome accounts for about 2% of orofacial clefts. The clinical and
      histomorphological aspects of VWS are studied, and a case of heterozygous female
      twins of whom only one was affected with VWS is reported. CONCLUSION: This very
      rare case (no similar case has been reported to date) contributes further
      evidence on modifying factors in the expression of this condition.

PMID- 29569459
TI  - A video eyeglasses/earphones system as distracting method during dental treatment
      in children: A crossover randomised and controlled clinical trial.
AB  - : AIM To evaluate the effectiveness of a Video Eyeglasses/Earphones System (VEES)
      as distracting device in reducing anxiety in children during dental procedures
      carried out under local anaesthesia. MATERIALS AND METHODS: In this crossover
      clinical trial, 36 Frankl scale II and III children aged 5-8 years received
      different dental procedures in two sessions, with and without the VEES system. In
      the control visit, they were not exposed to this distraction stimulus, but
      traditional non-aversive behaviour management was applied. Each dental session
      was divided into four phases (explanation, anaesthetic injection, rubber
      dam/clamp placement, and high-speed hand piece work for 5 min). Pain in each
      treatment phase was assessed by the following measurements: the Face, Legs,
      Activity, Cry, Consolability (FLACC) scale. Pulse rate, and oxygen saturation
      measurements were employed to evaluate the state of anxiety. Comparison of the
      outcomes of two interventions were statistically analysed through the Wilcoxon
      Signed-rank Test. RESULTS: There were no statistical differences between the
      results of the two interventions (VEES vs. no VEES/behavioural management) during
      the four treatment phases on assessment by any of the measurements employed.
      CONCLUSIONS: The VEES method was not more effective than traditional non-aversive
      behavioural techniques for reducing anxiety and pain perception in children
      undergoing dental treatment.

PMID- 29569460
TI  - Dental Sealants. Part 1: Prevention First.
AB  - BACKGROUND: Tooth decay is still one of the most common chronic childhood
      diseases in the world, even if during the last five decades measures to combat
      dental caries have been developed, tested and applied in many populations.
      Preventive care and education programmes are essential to keeping children's
      mouths healthy. Within the prevention methods, dental sealants play an important
      role in preventing the onset and the development of dental cavities.

PMID- 29569461
TI  - Influence of Occupational Socialization on the Perspectives and Practices of
      Adapted Physical Education Teachers.
AB  - The purpose of this study was to describe and examine the occupational
      socialization of nine adapted physical educators (APEs). The questions we
      attempted to answer were (a) What were the perspectives and practices of the
      APEs? and (b) What factors influenced these perspectives and practices? Data were
      collected through six qualitative techniques and analyzed by using analytic
      induction and constant comparison. At the time the study was conducted, the APEs
      possessed traditional or progressive teaching orientations. They had been
      attracted to a career as an APE through their participation in sport and physical
      activity and interactions with persons with disabilities. The quality of adapted
      physical education teacher education the APEs received varied, but high-quality
      adapted physical education teacher education appeared to exert a powerful
      influence on their values and pedagogies. The school cultures and conditions in
      which the APEs worked on entry into the workforce either served to support or
      negate their programs. We conclude the paper by providing several hypotheses
      regarding the influences of occupational socialization on in-service APEs'
      teaching.

PMID- 29569462
TI  - Conceptualizing Obesity as a Chronic Disease: An Interview With Dr. Arya Sharma.
AB  - Dr. Arya M. Sharma challenges the conventional wisdom of relying simply on
      "lifestyle" approaches involving exercise, diet, and behavioral interventions for
      managing obesity, suggesting that people living with obesity should receive
      comprehensive medical interventions similar to the approach taken for other
      chronic diseases such as Type 2 diabetes or hypertension. He purports that the
      stigma-inducing focus on self-failing (e.g., coping through food, laziness, lack
      of self-regulation) does not address biological processes that make obesity a
      lifelong problem for which there is no easy solution. Interdisciplinary
      approaches to obesity are advocated, including that of adapted physical activity.
      Physical activity has multifaceted impacts beyond increasing caloric expenditure,
      including improved sleep, better mood, increased energy levels, enhanced self
      esteem, reduced stress, and an enhanced sense of well-being. The interview with
      Dr. Sharma, transcribed from a keynote address delivered at the North American
      Adapted Physical Activity Symposium on September 22, 2016, in Edmonton, AB,
      Canada, outlines his rationale for approaching obesity as a chronic disease.

PMID- 29569463
TI  - Gradient-echo-based 3D submillisecond echo time pulmonary MR imaging: a
      preliminary usability study on clinical and preclinical MR scanners.
AB  - OBJECTIVE: To preliminarily investigate a technical feasibility of a
      submillisecond echo time concurrent-dephasing-and-excitation (CODE) sequence for
      pulmonary MRI on clinical and preclinical MR scanners Methods: CODE imaging (echo
      time, 0.14 ~ 0.18 ms) was performed with American College of Radiology phantom at
      3 T, 7 healthy volunteers at 1.5 and 3 T, 10 rabbits at 3 T, and 2 rodents at 9.4
      T. Signal-to-noise ratio was compared in phantom. Image quality of human MRI was
      visually assessed on a 5-point scale for comparison between CODE and conventional
      lung MRI sequences. Visibility of bronchi, subcentimeter nodules, and MR air
      bronchogram were assessed in animal studies. RESULTS: In phantom study, signal-to
      noise ratio was higher with CODE than with original three-dimensional ultrashort
      echo time sequence (106.71 +/- 4.32 vs 91.66 +/- 3.54; p < 0.001). Image quality
      of human MRI was better with CODE than with conventional MRI sequences (p <=
      0.002). Bronchi remained traceable up to the fifth bronchial generation in CODE
      images in rabbits and rodents. 95.2% of metastatic nodules (diameter, 1.5 +/- 0.4
      mm) and 93.8% of MR air-bronchogram (diameter, 0.9 +/- 0.2 mm) in rabbits.
      CONCLUSION: Submillisecond echo time pulmonary MRI was technically feasible by
      using CODE on various MR scanners. Advances in knowledge: CODE can be a practical
      alternative for lung MRI on both clinical and pre-clinical scanners, without
      challenges of free-induction-decay-based ultrashort-echo time sequences.

PMID- 29569464
TI  - Forensic Discrimination of Latent Fingerprints Using Laser-Induced Breakdown
      Spectroscopy (LIBS) and Chemometric Approaches.
AB  - A novel technique is reported for separating overlapping latent fingerprints
      using chemometric approaches that combine laser-induced breakdown spectroscopy
      (LIBS) and multivariate analysis. The LIBS technique provides the capability of
      real time analysis and high frequency scanning as well as the data regarding the
      chemical composition of overlapping latent fingerprints. These spectra offer
      valuable information for the classification and reconstruction of overlapping
      latent fingerprints by implementing appropriate statistical multivariate
      analysis. The current study employs principal component analysis and partial
      least square methods for the classification of latent fingerprints from the LIBS
      spectra. This technique was successfully demonstrated through a classification
      study of four distinct latent fingerprints using classification methods such as
      soft independent modeling of class analogy (SIMCA) and partial least squares
      discriminant analysis (PLS-DA). The novel method yielded an accuracy of more than
      85% and was proven to be sufficiently robust. Furthermore, through laser scanning
      analysis at a spatial interval of 125 um, the overlapping fingerprints were
      reconstructed as separate two-dimensional forms.

PMID- 29569465
TI  - Biomarker use in lung cancer management: expanding horizons.

PMID- 29569466
TI  - Heating Effects of Desi Ghee Using Raman Spectroscopy.
AB  - Raman spectroscopy as a fast and nondestructive technique has been used to
      investigate heating effects on Desi ghee during frying/cooking of food for the
      first time. A temperature in the range of 140-180C has been investigated within
      which Desi ghee can be used safely for cooking/frying without much alteration of
      its natural molecular composition. In addition, heating effects in case of reuse,
      heating for different times, and cooking inside pressure cookers are also
      presented. An excitation laser at 785 nm has been used to obtain Raman spectra
      and the range of 540-1800 cm-1 is found to contain prominent spectral bands.
      Prominent variations have been observed in the Raman bands of 560-770 cm-1, 790
      1160 cm-1, and 1180-1285 cm-1 with the rise in temperature. The spectral
      variations have been verified using classifier principal component analysis. It
      has been found that Desi ghee can be reused if heated below 180C and it can be
      heated up to 30 min without any appreciable molecular changes if a controlled
      heating can be managed.

PMID- 29569467
TI  - Momentum: A Report on the 2017 Vizient Clinical Connections Summit.

PMID- 29569468
TI  - Relationship between uric acid levels and cardiometabolic findings in a large
      cohort of beta-thalassemia major patients.
AB  - AIM: to evaluate the relationship between uric acid (UA), hepatic and cardiac
      iron overload (T2*-MRI), ferritin, endocrinological diseases and cardiac
      complications in a large thalassemia major (TM) cohort. METHODS:  A total of 369
      TM patients (187 men; 33 +/- 6 years) were retrospectively studied, from the
      myocardial iron overload in thalassemia (MIOT) electronic databank. RESULTS:
      Multiple regression model identified male sex (p < 0.001), BMI (p < 0.001) and
      T2* (p <= 0.001) as UA independent correlates. Moreover, UA and derivatives of
      reactive oxygen species (an oxidative index; r = -0.3; p <= 0.05) are inversely
      correlated. Conversely, the multivariate logistic analysis identified low UA
      (NANHES-III criteria) as one independent predictor for low global heart T2* (p <
      0.5) together with liver iron concentrations (>3 mg/g/dw), heart failure,
      endocrinopathies, ferritin (>2000 ng/l), alanine transaminase (>40 UI/l) and/or
      aspartate transaminase (>35 UI/l) and/or glutamyl transferase (>64 UI/l).
      DISCUSSION: UA appears directly associated to T2* and inversely with derivatives
      of reactive oxygen species, and as such reduced according to increased oxidative
      stress and cardiac iron overload in TM patients.

PMID- 29569469
TI  - Mach-Zehnder Stationary Two-Beam Spectroscopy Using Compound Prisms.
AB  - An interferometric optical setup for diffraction-less spectroscopy is tested as
      an optical design for control of interference frequency. Its design is based on a
      Mach-Zehnder interferometer in which a pair of compound prisms is introduced in
      the interferometer path to obtain interference patterns, which avoids the
      diffraction phenomena and nonlinear dispersion found on spectrometers that use
      gratings. Computer simulations of the interference patterns generated by the
      proposed optical setup are presented, and confirmed by the experimental results
      of the optical implementation. The theory that describes an ideal optical setup
      and the experimental results show that in order to reduce the combined
      uncertainties of wavelength measurement, a precise control in angle deviation and
      magnification are required for the reduction of measurement uncertainties.

PMID- 29569470
TI  - A trial based economic evaluation of occupational therapy discharge planning for
      older adults: the HOME randomized trial.
AB  - OBJECTIVE: To compare the cost effectiveness of two occupational therapy-led
      discharge planning interventions from the HOME trial. DESIGN: An economic
      evaluation was conducted within the superiority randomized HOME trial to assess
      the difference in costs and health-related outcomes associated with the enhanced
      program and the in-hospital consultation. Total costs of health and community
      service utilization were used to calculate incremental cost-effectiveness ratios,
      activities of daily living and quality-adjusted life years. SETTING: Medical and
      acute care wards of Australian hospitals ( n=5). SUBJECTS: A total of 400 people
      >= 70 years of age. INTERVENTIONS: Participants were randomized to either (1) an
      enhanced program (HOME), involving pre/post discharge visits and two follow-up
      phone calls, or (2) an in-hospital consultation using the home and community
      environment assessment and the Lawton Instrumental Activities of Daily Living
      assessment. MAIN MEASURES: Nottingham Extended Activities of Daily Living (global
      measure of activities of daily living) and SF-12V2, transformed into SF-6D
      (quality-adjusted life year) measured at baseline and three months post
      discharge. RESULTS: The cost of the enhanced program was higher than that of the
      in-hospital consultation. However, a higher proportion of patients showed
      improvement in activities of daily living in the enhanced program with an
      incremental cost-effectiveness ratio of $61,906.00 per person with clinically
      meaningful improvement. CONCLUSION: Health services would not save money by
      implementing the enhanced program as a routine intervention in medical and acute
      care wards. Future research should incorporate longer time horizons and consider
      which patient groups would benefit from home visits.

PMID- 29569471
TI  - Synthesis and bioactivities of diamide derivatives containing a phenazine-1
      carboxamide scaffold.
AB  - Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series
      of novel phenazine-1-carboxylic acid diamide derivatives were designed and
      synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays
      showed that some of the target compounds exhibited promising in vitro fungicidal
      activities, and exhibited excellent and selective herbicidal activities.
      Particularly, compounds c, h, o and s displayed root length inhibition activities
      against barnyard grass with the rate of more than 80%. Compound c exhibited the
      best activity among all the target compounds against barnyard grass stalk length
      with the IC50 value of 0.158 mmol/L, and compound o exhibited the best and wide
      spectrum inhibition against barnyard grass root length and rape in both root
      length and stalk length herbicidal activities with its IC50 values of 0.067,
      0.048 and 0.059 mmol/L respectively. The analysis of preliminary Structure
      Activity Relationships provides the theoretical basis for further design of
      phenazine-1-carboxylic acid.

PMID- 29569472
TI  - Regorafenib in the treatment of metastatic colorectal cancer.
AB  - Regorafenib is an orally available multikinase inhibitor, currently approved in
      metastatic chemorefractory colorectal cancer patients. The results of two large
      randomized Phase III trials are available, providing significant results in
      overall and progression-free survival in this situation. Its use requires a
      special attention regarding patient selection, dosing schedule and management of
      adverse events. Identifying patients who will tolerate and have benefit from
      regorafenib is a challenge for clinicians. Therapeutic monitoring (especially
      cfDNA), predictive biomarkers and specific perfusion-based imaging techniques
      will may be result in optimizing regorafenib treatment.

PMID- 29569473
TI  - Neurofeedback-Based Enhancement of Single-Trial Auditory Evoked Potentials:
      Treatment of Auditory Verbal Hallucinations in Schizophrenia.
AB  - Auditory verbal hallucinations depend on a broad neurobiological network ranging
      from the auditory system to language as well as memory-related processes. As part
      of this, the auditory N100 event-related potential (ERP) component is attenuated
      in patients with schizophrenia, with stronger attenuation occurring during
      auditory verbal hallucinations. Changes in the N100 component assumingly reflect
      disturbed responsiveness of the auditory system toward external stimuli in
      schizophrenia. With this premise, we investigated the therapeutic utility of
      neurofeedback training to modulate the auditory-evoked N100 component in patients
      with schizophrenia and associated auditory verbal hallucinations. Ten patients
      completed electroencephalography neurofeedback training for modulation of N100
      (treatment condition) or another unrelated component, P200 (control condition).
      On a behavioral level, only the control group showed a tendency for symptom
      improvement in the Positive and Negative Syndrome Scale total score in a pre
      /postcomparison ( t(4) = 2.71, P = .054); however, no significant differences
      were found in specific hallucination related symptoms ( t(7) = -0.53, P = .62).
      There was no significant overall effect of neurofeedback training on ERP
      components in our paradigm; however, we were able to identify different learning
      patterns, and found a correlation between learning and improvement in auditory
      verbal hallucination symptoms across training sessions ( r = 0.664, n = 9, P =
      .05). This effect results, with cautious interpretation due to the small sample
      size, primarily from the treatment group ( r = 0.97, n = 4, P = .03). In
      particular, a within-session learning parameter showed utility for predicting
      symptom improvement with neurofeedback training. In conclusion, patients with
      schizophrenia and associated auditory verbal hallucinations who exhibit a
      learning pattern more characterized by within-session aptitude may benefit from
      electroencephalography neurofeedback. Furthermore, independent of the training
      group, a significant spatial pre-post difference was found in the event-related
      component P200 ( P = .04).

PMID- 29569474
TI  - S100A11 promotes TGF-beta1-induced epithelial-mesenchymal transition through
      SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma.
AB  - AIM: Our previous study found S100A11 was significantly raised in intrahepatic
      cholangiocarcinoma cells, but the relationship between S100A11 and intrahepatic
      cholangiocarcinoma remains unclear. METHODS: We investigated the effect of
      silencing S100A11 on TGF-beta1-induced epithelial-mesenchymal transition (EMT),
      cell migration and invasion. RESULTS: Our results demonstrated silencing S100A11
      inhibited TGF-beta1-induced cell migration, invasion and EMT, expression of EMT
      markers E-cadherin, N-cadherin, beta-catenin, vimentin, Slug and Snail was
      reversed. Furthermore, TGF-beta1-induced p-SMAD2 and 3 were also inhibited due to
      low S100A11 expression. CONCLUSION: Our present study indicated that S100A11
      promotes EMT through accumulation of TGF-beta1 expression, and TGF-beta1-induced
      upregulation of p-SMAD2 and 3.

PMID- 29569475
TI  - Association of monocyte to high-density lipoprotein cholesterol ratio with
      carotid artery intima-media thickness in patients with systemic lupus
      erythematosus.
AB  - AIM: The purpose of this study was to evaluate the relationship between monocyte
      to high-density lipoprotein cholesterol ratio (MHR) and carotid atherosclerostic
      plaque in patients with systemic lupus erythematosus (SLE). METHODS: A total of
      214 SLE patients were divided into two groups according to the results of
      ultrasonic examination: carotid arterial atherosclerotic plaque groups and
      noncarotid arterial atherosclerosis groups. RESULTS: The values of monocyte to
      high-density lipoprotein-cholesterol ratio (MHR) increase in carotid arterial
      atherosclerotic plaque groups compared with noncarotid arterial atherosclerosis
      groups (0.32 +/- 0.18 vs 0.26 +/- 0.15; p = 0.015). There was a significant
      correlation between MHR and carotid artery intima-media thickness (r = 0.228; p =
      0.001) in patients with SLE. CONCLUSION: Our study suggests that the values of
      MHR could be a marker to assess carotid artery intima-media thickness in patients
      with SLE.

PMID- 29569476
TI  - Surgery option in the management of delayed diplopia after radiation therapy for
      nasopharyngeal carcinoma.
AB  - PURPOSE: Radiation therapy is a standard treatment for nasopharyngeal carcinoma.
      Diplopia due to radiation damage to the sixth nerve significantly erodes the
      patient's quality of life. This study investigated the effectiveness of
      extraocular surgery in the treatment of delayed diplopia caused by radiation
      therapy. METHODS: A retrospective case series of 16 patients (7 men and 9 women)
      with delayed diplopia after radiation therapy for nasopharyngeal carcinoma was
      enrolled in the study. Unilateral lateral rectus resection was performed under
      topical anesthesia. Follow-up time was more than 12 months. Outcome measures were
      prism diopter and self-reported symptoms. RESULTS: All patients diagnosed with
      sixth nerve palsy reported elimination of symptoms on postoperative day 1 without
      complications. One patient required a second procedure due to recurrence of
      symptoms. At 12-month follow-up, no patient reported recurrence of symptoms. The
      absolute horizontal deviation significantly decreased from a preoperative value
      of 16 prism diopter to a value of 1.5 prism diopter postoperatively (p < 0.001).
      CONCLUSION: These results suggest that unilateral lateral rectus resection under
      topical anesthesia is an effective treatment for delayed diplopia after radiation
      therapy for nasopharyngeal carcinoma. A large randomized prospective study to
      confirm these findings is warranted.

PMID- 29569477
TI  - Optical coherence tomography angiography and choroidal neovascularization in
      multifocal choroiditis: A descriptive study.
AB  - PURPOSE: To analyze the ability of optical coherence tomography angiography to
      identify choroidal neovascularization in multifocal choroiditis and to describe
      active and inactive choroidal neovascularization findings. METHODS: Retrospective
      study of consecutive patients with multifocal choroiditis and choroidal
      neovascularization examined between January and November 2016. In addition to
      usual exams, optical coherence tomography angiography (AngioPlexTM CIRRUSTM HD
      OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, CA, USA) images were assessed
      for morphological analysis: choroidal neovascularization size, choroidal
      neovascularization margin (well or poorly circumscribed), choroidal
      neovascularization shape (tangled or interlacing), choroidal neovascularization
      core (feeder vessel) and dark ring around the choroidal neovascularization.
      RESULTS: A total of 10 eyes were included. Optical coherence tomography
      angiography identified all choroidal neovascularization. Active choroidal
      neovascularization had well-circumscribed margins (67%), interlacing shape (83%),
      and a surrounding dark ring (83%). Inactive choroidal neovascularization had
      rather poorly circumscribed margins (75%), tangled shape, and "dead tree"
      appearance (50%) with less frequently a surrounding dark ring (50%). CONCLUSION:
      Optical coherence tomography angiography is adapted to confirm the diagnosis of
      choroidal neovascularization complicating multifocal choroiditis, but it is still
      insufficient to differentiate active and inactive lesions.

PMID- 29569478
TI  - Evaluation of hyaloid-retinal relationship during triamcinolone-assisted
      vitrectomy for primary rhegmatogenous retinal detachment.
AB  - AIMS: To determine hyaloid-retinal relationship in primary rhegmatogenous retinal
      detachment during vitreous surgery. METHODS: This is a prospective,
      interventional study of patients (n = 72) undergoing triamcinolone-assisted 25G
      vitreous surgery for primary rhegmatogenous retinal detachment. Hyaloid-retinal
      relationship was noted intraoperatively to identify regions and patterns of firm
      attachment and was classified into subgroups. Analysis was done to determine
      association between hyaloid-retinal relationship patterns and preoperative
      findings: posterior vitreous detachment, proliferative vitreoretinopathy, type of
      retinal tear, the presence of peripheral degenerations, and postoperative
      outcomes. RESULTS: Three patterns of hyaloid-retinal relationship were
      identified: type1 (complete absence of posterior vitreous detachment (21%)), type
      2 (incomplete posterior vitreous detachment (47%)) and type 3 (complete posterior
      vitreous detachment (32%)). Posterior vitreous detachment in some form was
      present in 84% of the cases with retinal tears as the causative break but none of
      the cases with retinal holes (p < 0.001). None of the cases with vitreoretinal
      degeneration had complete posterior vitreous detachment (p = 0.001). 69% of
      proliferative vitreoretinopathy-C cases had type 1 hyaloid-retinal relationship
      as compared to 11% cases with no proliferative vitreoretinopathy (p < 0.001).
      Proliferative vitreoretinopathy-related anatomical failure was seen in 7.5%, and
      80% of these eyes with recurrent RD had type 1 hyaloid-retinal relationship
      (p<0.001). Nearly half the patients diagnosed as complete posterior vitreous
      detachment preoperatively were found to have incomplete posterior vitreous
      detachment intraoperatively. CONCLUSIONS: Majority of the cases with
      rhegmatogenous retinal detachment have some form of strong vitreoretinal
      adhesion. Hyaloid-retinal relationship varies with types of retinal breaks,
      retinal degeneration, and proliferative vitreoretinopathy. Intraoperative hyaloid
      retinal relationship is frequently different from that assessed before surgery
      and the proposed classification may improve surgical decision making and
      prognostication.

PMID- 29569479
TI  - Comparing capsular bag performance of a hydrophilic and a hydrophobic intraocular
      lens: A randomised two-centre study.
AB  - PURPOSE:: To evaluate the capsular bag performance and posterior capsule
      opacification development of two intraocular lenses differing in material and
      design. METHODS:: This study included patients who were scheduled for cataract
      surgery and compared a hydrophilic intraocular lens (Super flex(r) intraocular
      lens; Rayner Surgical, Worthing, UK) with a hydrophobic intraocular lens
      (AcrySof(r) SA60AT; Alcon, Fort Worth, TX, USA). Follow-ups were performed 1
      month and 2 years after cataract surgery, including a slit lamp examination and
      retroillumination images. RESULTS:: In total, 80 eyes of 80 patients were
      recruited. At the 1-month follow-up, 6 of 39 cases had a gap between the
      posterior lens capsule and intraocular lens (1 case in the hydrophilic
      intraocular lens group and 5 cases in the hydrophobic intraocular lens group; p =
      0.348). Objective and subjective posterior capsule opacification scoring showed
      no statistically significant difference between both groups (p = 0.123).
      CONCLUSION:: Both intraocular lens showed a good capsular bag performance and a
      relatively low posterior capsule opacification development within the first 2
      years after surgery.

PMID- 29569481
TI  - 2017 Reviewers.

PMID- 29569480
TI  - ACMQ: Advancing the Field of Medical Quality.

PMID- 29569482
TI  - Classification of miRNA-related sequence variations.
AB  - miRNA regulome is whole set of regulatory elements that regulate miRNA expression
      or are under control of miRNAs. Its understanding is vital for comprehension of
      miRNA functions. Classification of miRNA-related genetic variability is
      challenging because miRNA interact with different genomic elements and are
      studied at different omics levels. In the present study, miRNA-associated genetic
      variability is presented at three levels: miRNA genes and their upstream
      regulation, miRNA silencing machinery and miRNA targets. Several types of miRNA
      associated genetic variations are known, including short and structural
      polymorphisms and epimutations. Differential expression can also affect miRNA
      regulome function. Classification of miRNA-associated genetic variability
      presents a baseline for complementing sequence variant nomenclature, planning of
      experiments, protocols for multi-omics data integration and development of
      biomarkers.

PMID- 29569483
TI  - Pathological assessment of gastrointestinal biopsies from patients with
      idelalisib-associated diarrhea and colitis.
AB  - AIM: Idelalisib (IDELA) treatment is associated with diarrhea/colitis (incidence
      of ~15% grade >=3). We performed a retrospective analysis of gastrointestinal
      biopsies from 29 patients treated with IDELA across nine clinical trials.
      METHODS: A central core laboratory performed histopathologic review,
      immunohistochemistry, and droplet digital PCR viral studies. These results were
      correlated with tissue immune profiling data and morphologic features per
      modified Geboes score. RESULTS: Out of 29 eligible patients with abdominal pain
      or diarrhea, 24 (82.8%) had reported adverse event terms of diarrhea and/or
      colitis. Infectious pathogens were detected in 9/29 samples. Most biopsies
      presented with mixed/inflammatory infiltrates and contained increased numbers of
      FOXP3+ cells versus normal controls. CONCLUSION: This study revealed evidence of
      T-cell dysregulation and a substantial infectious component in association with
      IDELA-related diarrhea/colitis.

PMID- 29569484
TI  - Two new phenylspirodrimanes from the deep-sea derived fungus Stachybotrys sp.
      MCCC 3A00409.
AB  - Two new phenylspirodrimanes, stachybotrin H (1) and stachybotrysin H (9) together
      with eleven known analogues (2-8, 10-13) were isolated from deep-sea derived
      Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR
      data and mass spectroscopic analysis. Compounds 9-12 showed weak cytotoxicity
      against three human cancer cell lines K562, Hela and HL60 with IC50 in the range
      of 18.5-52.8 MUM.

PMID- 29569485
TI  - New dihydrophenanthrenes from Dendrobium infundibulum.
AB  - Two new dihydrophenanthrenes, dendroinfundin A (1) and dendroinfundin B (2) were
      isolated from the whole plant of Dendrobium infundibulum, together with 7 known
      compounds (3-9). The structures of the new compounds (1 and 2) were established
      on the basis of their spectroscopic data. All of the isolates were evaluated for
      their alpha-glucosidase and pancreatic lipase inhibitory activities. Batatasin
      III (5) and dendrosinen B (9) showed strong alpha-glucosidase inhibitory
      activity. Dendrosinen B (9) also exhibited appreciable pancreatic lipase
      inhibitory effect.

PMID- 29569486
TI  - Pharmacoepigenetics in childhood acute lymphoblastic leukemia: involvement of
      miRNA polymorphisms in hepatotoxicity.
AB  - AIM: Hepatotoxicity is one of the most common drug-related toxicities during the
      treatment of childhood acute lymphoblastic leukemia (ALL). Many genes involved in
      liver-specific signaling pathways are tightly controlled by miRNAs, and miRNA
      function could be modulated by SNPs. As a consequence, we hypothesized that
      variants in miRNAs could be associated with drug-induced hepatotoxicity. METHODS:
      We analyzed 213 SNPs in 206 miRNAs in a cohort of 179 children with ALL
      homogeneously treated. RESULTS: rs2648841 in miR-1208 was the most significant
      SNP during consolidation phase after false discovery rate correction, probably
      through an effect on its target genes DHFR, MTR and MTHFR. CONCLUSION: These
      results point out the possible involvement of SNPs in miRNAs in toxicity to
      chemotherapy in children with ALL.

PMID- 29569487
TI  - Human and experimental toxicology of diquat poisoning: Toxicokinetics, mechanisms
      of toxicity, clinical features, and treatment.
AB  - Diquat (1,1'-ethylene-2,2'-bipyridinium ion; DQ) is a nonselective quick-acting
      herbicide, which is used as contact and preharvest desiccant to control
      terrestrial and aquatic vegetation. Several cases of human poisoning were
      reported worldwide mainly due to intentional ingestion of the liquid
      formulations. Its toxic potential results from its ability to produce reactive
      oxygen and nitrogen species through redox cycling processes that can lead to
      oxidative stress and potentially cell death. Kidney is the main target organ due
      to DQ toxicokinetics and redox cycling. There is no antidote against DQ
      intoxications, and the efficacy of treatments currently applied is still
      unsatisfactory. The aim of this work was to review the most relevant human and
      experimental findings related to DQ, characterizing its chemistry, activity as
      herbicide, mechanisms of toxicity, consequences of poisoning, and potential
      therapeutic approaches taking into account previous experience in developing
      antidotes for paraquat, a more toxic bipyridinium herbicide.

PMID- 29569489
TI  - Catatonia: Stereotypies, mannerisms and perseverations.

PMID- 29569488
TI  - Structural and functional properties of bone are compromised in amyotrophic
      lateral sclerosis mice.
AB  - In addition to muscle weakness, amyotrophic lateral sclerosis (ALS) is associated
      with an increased incidence of skeletal fractures. The SOD1G93A mouse model
      recapitulates many features of human ALS. These mice also exhibit decreased bone
      mass. However, the functional, or biomechanical, behavior of the skeleton in
      SOD1G93A mice has not been investigated. To do so, we examined skeletal
      phenotypes in end-stage (16-week-old) SOD1G93A female mice and healthy littermate
      female controls (N = 9-10/group). Outcomes included trabecular and cortical bone
      microarchitecture by microcomputed tomography; stiffness and strength via three
      point bending; resistance to crack growth by fracture toughness testing; and
      cortical bone matrix properties via cyclic reference point indentation. SOD1G93A
      mice had similar bone size, but significantly lower trabecular bone mass (-54%),
      thinner trabeculae (-41%) and decreased cortical bone thickness (-17%) and
      cortical area (-18%) compared to control mice (all p < 0.01). In line with these
      bone mass and microstructure deficits, SOD1G93A mice had significantly lower
      femoral bending stiffness (-27%) and failure moment (-41%), along with decreased
      fracture toughness (-18%) (all p < 0.001). This is the first study to demonstrate
      functional deficits in the skeleton of end-stage ALS mice, and imply multiple
      mechanisms for increased skeletal fragility and fracture risk in patients in ALS.
      Importantly, our results provide strong rationale for interventions to reduce
      fracture risk in ALS patients with advanced disease.

PMID- 29569490
TI  - The ambulances at the top of the cliff.

PMID- 29569491
TI  - Acupuncture for heart disease patients.

PMID- 29569492
TI  - A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with
      or without statins for cardiovascular outcomes.
AB  - Background The comparative effects of statins, ezetimibe with or without statins
      and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain
      unassessed. Design Bayesian network meta-analysis was conducted to compare
      treatment groups. Methods Thirty-nine randomized controlled trials were selected
      using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In
      network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the
      best treatment for prevention of major adverse cardiovascular events (Surface
      Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%)
      and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse
      cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72;
      95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment,
      Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95%
      CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49-0.79;
      GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major
      adverse cardiovascular event reduction in secondary prevention trials (SUCRA,
      95%). Statins had the highest probability of having lowest rates of all-cause
      mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with
      placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83
      0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77
      0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as
      the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA,
      50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for
      reducing major adverse cardiovascular events, myocardial infarction and stroke,
      without having major safety concerns. Statins were ranked as the most effective
      therapy for reducing mortality.

PMID- 29569493
TI  - How to design carbohydrate diet regimens for heart disease patients.

PMID- 29569495
TI  - Editor's Presentation.

PMID- 29569494
TI  - N-terminal fraction of pro-B-type natriuretic peptide versus clinical risk scores
      for prognostic stratification in chronic systolic heart failure.
AB  - Background The Seattle heart failure model or the cardiac and comorbid conditions
      (3C-HF) scores may help define patient risk in heart failure. Direct comparisons
      between them or versus N-terminal fraction of pro-B-type natriuretic peptide (NT
      proBNP) have never been performed. Methods Data from consecutive patients with
      stable systolic heart failure and 3C-HF data were examined. A subgroup of
      patients had the Seattle heart failure model data available. The endpoints were
      one year all-cause or cardiovascular death. Results The population included 2023
      patients, aged 68 +/- 12 years, 75% were men. At the one year time-point, 198
      deaths were recorded (10%), 124 of them (63%) from cardiovascular causes. While
      areas under the curve were not significantly different, NT-proBNP displayed
      better reclassification capability than the 3C-HF score for the prediction of one
      year all-cause and cardiovascular death. Adding NT-proBNP to the 3C-HF score
      resulted in a significant improvement in risk prediction. Among patients with
      Seattle heart failure model data available ( n = 798), the area under the curve
      values for all-cause and cardiovascular death were similar for the Seattle heart
      failure model score (0.790 and 0.820), NT-proBNP (0.783 and 0.803), and the 3C-HF
      score (0.770 and 0.800). The combination of the 3C-HF score and NT-proBNP
      displayed a similar prognostic performance to the Seattle heart failure model
      score for both endpoints. Adding NT-proBNP to the Seattle heart failure model
      score performed better than the Seattle heart failure model alone in terms of
      reclassification, but not discrimination. Conclusions Among systolic heart
      failure patients, NT-proBNP levels had better reclassification capability for all
      cause and cardiovascular death than the 3C-HF score. The inclusion of NT-proBNP
      to the 3C-HF and Seattle heart failure model score resulted in significantly
      better risk stratification.

PMID- 29569496
TI  - Development of carbazole-bearing pyridopyrimidine-substituted urea/thiourea as
      polyphenol oxidase inhibitors: synthesis, biochemistry, and theoretical studies.
AB  - Polyphenol oxidase (Tyrosinase, PPO) has received considerable attention, since
      it is the key enzyme in melanin biosynthesis. In this study, we investigated
      prepared novel carbazole-containing pyridopyrimidine-substituted with urea and
      thiourea derivatives and their PPO activities on the diphenolase activity of
      banana tyrosinase. The structures of the compounds synthesized were confirmed by
      1 H NMR, 13 C NMR, FTIR and elemental analysis. PPO enzyme was purified from
      banana on an affinity gel comprised of Sepharose 4B-L-tyrosine-p-amino benzoic
      acid. For evaluating the enzyme activity, the synthesised compounds were
      subjected to tyrosinase inhibition assay using catechol as substrate. While some
      of the compounds (6, 7, 8f, 8h, 8i, 8j) showed enzyme inhibitor effect, some of
      them (8a, 8b, 8c, 8d, 8e, 8g, 8k) activated the PPO enzyme activity. Gaussian
      software was used for the molecular calculations to explain the results for the
      prepared compounds.

PMID- 29569497
TI  - Racial and ethnic disparities in stroke outcomes: a scoping review of post-stroke
      disability assessment tools.
AB  - PURPOSE: To identify how post-stroke disability outcomes are assessed in studies
      that examine racial/ethnic disparities and to map the identified assessment
      content to the International Classification of Functioning, Disability, and
      Health (ICF) across the time course of stroke recovery. METHODS: We conducted a
      scoping review of the literature. Articles published between January 2001 and
      July 2017 were identified through Scopus, PubMed, CINAHL, and PsycINFO according
      to predefined inclusion and exclusion criteria. RESULTS: We identified 1791
      articles through database and hand-searching strategies. Of the articles, 194 met
      inclusion criteria for full-text review, and 41 met inclusion criteria for study
      inclusion. The included studies used a variety of outcome measures encompassing
      domains within the ICF: body functions, activities, participation, and contextual
      factors across the time course of stroke recovery. We discovered disproportionate
      representation among racial/ethnic groups in the post-stroke disability
      disparities literature. CONCLUSIONS: A wide variety of assessments are used to
      examine disparities in post-stroke disability across the time course of stroke
      recovery. Several studies have identified disparities through a variety of
      assessments; however, substantial problems abound from the assessments used
      including inconsistent use of assessments, lacking evidence on the validity of
      assessments among racial/ethnic groups, and inadequate representation among all
      racial/ethnic populations comprising the US. Implications for Rehabilitation An
      enhanced understanding of racial/ethnic disparities in post-stroke disability
      outcomes is inherently important among rehabilitation practitioners who
      frequently engage with racial/ethnic minority populations across the time course
      of stroke recovery. Clinicians should carefully consider the psychometric
      properties of assessment tools to counter potential racial bias. Clinicians
      should be aware that many assessments used in stroke rehabilitation lack cultural
      sensitivity and could result in inaccurate assessment findings.

PMID- 29569498
TI  - Educating children and adolescents about vaccines: a review of current
      literature.
AB  - INTRODUCTION: Until recently, research on vaccine hesitancy has focused primarily
      on parent populations. Although adolescent knowledge and views are gaining
      momentum within the literature, particularly with regards to the human
      papillomavirus and influenza, children remain a virtually unstudied population
      with regards to vaccine hesitancy. Areas Covered: This review focuses on the lack
      of literature in this area and argues for more vaccine hesitancy research
      involving child and adolescent populations. It also outlines special issues to
      consider when framing health promotion messages for children and adolescents.
      Finally, we explore the use of new and existing technologies as delivery
      mechanisms for education on vaccines and immunizations in populations of children
      and adolescents. Expert Commentary: Children undergo cognitive development and
      experiences with vaccines (e.g. pain or education) have the potential to create
      future attitudes toward vaccines. This can influence future vaccine behaviour,
      including their participation in decision-making around adolescent vaccines,
      their decisions to vaccinate themselves when they are adults, and their decisions
      to vaccinate their own children. Interventions aimed at children, such as
      education, can create positive attitudes toward vaccines. These can also
      potentially influence parental attitudes toward vaccines as children convey this
      knowledge to them. Both of these impacts require further study.

PMID- 29569499
TI  - Topically administered hyaluronic acid in the upper airway: A narrative review.
AB  - Hyaluronic acid plays a role in controlling inflammatory airway processes and
      mucociliary clearance, and it is also involved in tissue healing and remodelling.
      Some studies have tested the effectiveness of topically administered hyaluronic
      acid in patients with upper airway diseases with positive preliminary results.
      This article describes the use of topically administered hyaluronic acid in
      patients with otolaryngological disorders. Pertinent studies published between
      January 2000 and October 2016 were selected by means of a MEDLINE search using
      the following terms: 'hyaluronic acid' and 'otolaryngology', 'otitis',
      'pharyngitis', 'tonsillitis', 'rhinitis', 'rhinosinusitis' and 'nose'. Twelve of
      the 19 initially identified papers were selected, corresponding to 902 patients
      as a whole. There is some evidence that topically administered hyaluronic acid is
      effective or moderately effective in different otolaryngological conditions, as
      it improves the global subjective and clinical status of patients with
      inflammation of the nasopharyngeal and oto-tubaric complex, those with rhinitis
      or rhinosinusitis and those who have undergone nasal and sinonasal surgery.
      However, these findings should be viewed cautiously as they are based on a
      limited number of studies, some of which were probably under-powered because of
      their small patient samples.

PMID- 29569500
TI  - Mechanisms of action and clinical use of specific reversal agents for non-vitamin
      K antagonist oral anticoagulants.
AB  - OBJECTIVES: With a steadily growing number of patients with non-valvular atrial
      fibrillation, anticoagulation use increases. Anticoagulation therapy is
      associated with increased risk of serious bleeding and an increased complexity in
      management of patients in need for urgent surgery. We wanted to assess the
      magnitude of this challenge as well as review current and potential future
      clinical management strategies. DESIGN: A review of the literature on the
      magnitude of patients using antigoaculants in potential need for acute
      restoration of hemostasis was conducted, as well as current status of reversal
      agents for non-vitamin K antagonist oral anticoagulants (NOACs). Additionally, a
      case illustration of its use is presented. RESULTS: Two main groups of patients
      may need acute restoration of hemostasis, those in need of acute surgery or acute
      invasive procedures, ~ 2% of patients annually, and those with serious and
      critical hemorrhage, ~1.5% annually. One specific reversal agent is available on
      the market (idarucizumab) and two (andexanet alfa, ciraparantag) are in clinical
      development. Idarucizumab is a specific antidote for the thrombin inhibitor
      dabigatran while andexanet alfa is factor Xa inhibitor class-specific currently
      in late-stage development. Ciraparantag is a universal reversal agent in early
      phase development. These agents can facilitate effective management of bleeding
      or bleeding risk, as illustrated in a patient on dabigatran in urgent need for a
      pacemaker. CONCLUSIONS: Amongst patients using anticoagulants, around 3.5%, could
      be in need of immediate restoration of hemostasis annually. The availability and
      use of specific reversal agents for NOACs could be crucial for the clinical
      outcomes.

PMID- 29569503
TI  - Evolving models of collaborative drug discovery: managing intellectual capital
      assets.

PMID- 29569502
TI  - Tumor Size in Breast Carcinoma: Gross Measurement Is Important!
AB  - INTRODUCTION: The staging of breast carcinoma is mainly dependent on tumor size
      and lymph node status. Small increments in tumor size upstage the patient. An
      accurate determination of the tumor size is therefore critically important.
      Although the final staging is based on microscopic size, pathologists rely on
      gross measurements in a considerable number of cases. METHODS: We investigated
      the concordance between gross and microscopic measurements of breast carcinoma as
      well as factors affecting this concordance. This study is a retrospective review
      of surgical pathology reports of invasive breast carcinomas. Data were collected
      for 411 cases. Concordance was defined as a size difference within +/-2 mm.
      RESULTS: Gross and microscopic sizes were identical in 33.1% of cases. Gross and
      microscopic size difference was within +/-2 mm in 56% of cases. Despite the size
      difference, stage classification ended up being the same in 68.6% of cases. Tumor
      stage was over estimated by gross measurement in 17.0% of cases and
      underestimated in 14.4% of cases. The concordance was significantly higher for
      those tumors in which final pathologic tumor (pT) size was greater than 2 cm
      (>=pT2) as compared with those less than or equal to 2 cm (<=pT1; P < .0001). A
      higher proportion of mastectomy specimens (61.4%) were concordant as compared
      with lumpectomy specimens (52.1%). CONCLUSION: Gross and microscopic tumor sizes
      were concordant in 56% of cases. Stage classification based on gross and
      microscopic tumor size was different in nearly one third (31.4%) of cases. Gross
      tumor size is critically important in accurate staging at least in cases where
      tumor size cannot be confirmed microscopically.

PMID- 29569501
TI  - Being in control of Parkinson's disease: A qualitative study of community
      dwelling patients' coping with changes in care.
AB  - BACKGROUND: Chronically ill patients have to cope with transfers in the level or
      setting of care. Patients with prevalent disorders such as diabetes mellitus can
      be supported by their general practitioner (GP) when experiencing such care
      changes, as the GP already offers them disease-specific care. For community
      dwelling patients with low-prevalent diseases such as Parkinson's disease (PD) -
      for which disease-specific care is provided by medical specialists - tailoring
      support to handle care changes requires more insight into patients' coping.
      OBJECTIVES: To explore PD patients' coping with care changes. METHODS: A
      qualitative interview study was performed in 2013-2015 with a purposive sample of
      16 community-dwelling PD patients in the Netherlands. A research assistant
      visited patients every month to explore if they had experienced a care change. If
      so, patients were interviewed face-to-face. An inductive approach to comparative
      content analysis was used. RESULTS: Patients encountered a variety of care
      changes such as changes in the level of unpaid care, the purchase of tools,
      modification of pharmacotherapy or admission to hospital. Being able to
      anticipate, initiate and independently handle care changes contributes to
      patients' sense of control and acceptance of the post-change situation. Patients,
      who commenced care changes themselves, had more realistic expectations of it.
      CONCLUSION: Community-dwelling PD patients seem to be able to cope with the care
      changes they face. Offering education to facilitate their anticipation and
      initiation of changes in care and their ability to act independently, can
      contribute to patients' wellbeing. GPs can play a role in this.

PMID- 29569504
TI  - C1-esterase inhibitor (Cinryze(r)) use in the treatment of pediatric hereditary
      angioedema.
AB  - Hereditary angioedema (HAE) is a rare genetic disease resulting in unpredictable
      and potentially life-threatening subcutaneous and submucosal attacks mediated by
      the vasoactive peptide, bradykinin. HAE often presents within the first or second
      decade of life, with attacks increasing in both frequency and severity over time.
      First-line therapies exert their action by replacing C1 inhibitor (C1-INH) or via
      blocking the production or function of bradykinin. Cinryze(r) is a nanofiltered
      C1-INH, approved in Europe for the acute treatment, preprocedure prevention and
      routine prophylaxis of HAE attacks, and for routine prophylaxis of attacks in the
      USA. Of the current C1-INH preparations available, Cinryze shows particular
      promise in the safe and effective treatment and prophylaxis of HAE attacks in
      pediatric age patients.

PMID- 29569505
TI  - Risk factors associated with complications/sequelae of acute and subacute
      haematogenous osteomyelitis: an Italian multicenter study.
AB  - BACKGROUND: Acute/subacute haematogenous osteomyelitis (AHOM/SAHOM) are
      potentially devastating diseases. Updated information about the epidemiology,
      management and outcome of AHOM/SAHOM is needed to minimize the risk of
      complications and sequelae. METHODS: A multicenter study was performed to
      evaluate retrospectively the management and outcome of AHOM/SAHOM in Italy. Data
      from children aged >1 month, and hospitalized between 2010 and 2016, in 19
      pediatric centers, were analyzed. RESULTS: 300 children with AHOM and 98 with
      SAHOM were included. Median age was 6.0 years (IQR: 2.0-11.0). No clinical
      difference was observed with the exception of fever at onset (63.0% vs. 42.9%; P
      < 0.0001), and a more common spinal involvement in SAHOM (6.7% vs 20.4%; P <
      0.001). Fifty-Eight Staphylococcus aureus strains were isolated; 5 (8.6%) were
      MRSA. No Kingella kingae infection was documented. No different risk for
      complication/sequela was observed between AHOM and SAHOM (38.3% vs. 34.7%;
      OR:0.85; 95%CI: 0.53-1.38; P = 0.518). Duration and type of antibiotic therapy
      were not associated with risk of complication/sequelae. CONCLUSION: AHOM and
      SAHOM displayed some differences, however occurrence and risk factors for
      complications and sequelae are similar, and the same empiric treatment might be
      recommended.

PMID- 29569507
TI  - Poor agreement between repeated T-SPOT.TB in a short time period in a high TB
      burden country.

PMID- 29569508
TI  - Nanoparticle-based CpG-oligonucleotide therapy for treating allergic asthma.
AB  - Allergic asthma is becoming increasingly prevalent in the developed world, and
      many common allergens are capable of inducing allergic asthma responses,
      particularly in atopic individuals. Unmethylated CpG-oligonucleotide (ODN)
      therapy can shift the immune response to mitigate these allergic responses.
      Therapeutic and prophylactic delivery of soluble CpG-ODN in preclinical studies
      has shown promise in treating existing asthma and preventing allergic responses
      upon subsequent allergen exposure, respectively. However, when CpG-ODN is coupled
      with nanoparticles or self assembled into nanostructures, improved efficacy of
      CpG-ODN treatment for several common allergens is observed in preclinical studies
      and clinical trials. Here we discuss the role of CpG-ODN in treating allergic
      asthma and how nanoparticle-based delivery can further enhance its therapeutic
      properties.

PMID- 29569506
TI  - Impact of allergen immunotherapy in allergic asthma.
AB  - Although traditional pharmacological approaches improve outcomes in disease
      management for allergic asthma, these fail to modify the underlying immune
      responses. Allergen immunotherapy remains the only etiological therapy for the
      treatment of respiratory allergies for which clinical efficacy has been
      demonstrated through several well-controlled studies. In this review, we examine
      evidence from the past 5 years regarding the impact of allergen immunotherapy on
      allergic asthma to inform practitioners and stimulate further discussion and
      research.

PMID- 29569509
TI  - The future impacts of non-targeted effects.
AB  - Ionizing radiation was traditionally thought to exert its detrimental effects
      through interaction with sensitive cellular targets, nuclear DNA being of most
      importance. This theory has since merged with a more recently described radiation
      response called non-targeted effects (NTE). This review will briefly look at the
      various types of NTE and the potential implications they may have for
      radiobiology research and its applications. The most well-known NTE are genomic
      instability (GI) and bystander effects (BE). Other NTE include abscopal effects,
      which are similar to bystander effects but are generally based in a clinical
      environment with immune involvement as the defining feature. Currently, our
      understanding of NTE is limited to certain signaling pathways/molecules, and as
      yet there is no theory that describes or can accurately predict the occurrence or
      outcome of these NTE. There are numerous groups investigating these processes in
      vitro and in vivo, and thus steady progress is being made. Developing a deeper
      understanding of NTE has potential impacts for therapy and diagnosis, safer
      occupational exposures, space flight and our general understanding of radiation
      biology.

PMID- 29569510
TI  - Consequences of B-cell-depleting therapy: hypogammaglobulinemia and impaired B
      cell reconstitution.
AB  - Rituximab is a chimeric monoclonal antibody used to treat hematologic and
      autoimmune diseases by depleting CD20-expressing B cells. Patients may develop
      hypogammaglobulinemia following treatment, with some demonstrating failure of B
      cell recovery. The true frequency of hypogammaglobulinemia and/or impaired B-cell
      reconstitution post rituximab is unknown due to the lack of prospective studies
      in different patient cohorts. The clinical significance remains controversial;
      some patients have recurrent infections while others are relatively asymptomatic.
      The aim of this review is to describe the prevalence of hypogammaglobulinemia and
      the associated risk for developing severe infection, in patients with differing
      underlying clinical conditions treated with rituximab. This may facilitate
      classification and prognostication of patients who develop these conditions and
      identify patients who may be at high risk of developing these complications,
      including those who may benefit from immunoglobulin replacement therapy.

PMID- 29569511
TI  - Radioimmunotherapy as the first line of treatment in non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy. The
      estimated deaths and new cases of NHL in the USA in 2018 have reached 19,910 and
      74,680, respectively, with 5-year survival rate of 71%. Therapeutic interventions
      for NHL consist of chemotherapy, radiation therapy and immunotherapy.
      Radioimmunotherapy (RIT) is a potential alternative treatment for NHL that is
      currently used in different lines of treatment. Studies show that nuclear
      medicine physicians and radiation oncologists are not yet certain about the
      proper line for administration of RIT. Herein, we have reviewed the efficiency
      and toxicity of RIT as the first line of treatment, and discussed potential novel
      indications, and strategies such as modifying induction therapy and using
      rituximab maintenance to optimize the efficiency of RIT as the first line of
      treatment. Our review indicates that it is more logical to postpone conventional
      therapies to the second or third lines of treatment instead of RIT.

PMID- 29569512
TI  - Construction of a recombinant B-cell epitope vaccine based on a Der p1-derived
      hypoallergen: a bioinformatics approach.
AB  - AIM: House dust mite (HDM) allergens are important elicitors of IgE-mediated
      allergies. This study was aimed at constructing and characterizing a recombinant
      fusion protein, DpTTDp, which was based on carrier-bound Der p 1-derived peptides
      for HDM allergen immunotherapy. METHODS: Using the Immune Epitope Database
      (IEDB), we identified from Der p 1, a 34-mer hypoallergenic peptide. Two copies
      of the hypoallergen were then fused to a partial fragment of a tetanus toxoid
      molecule's N-and C terminus and expressed in Escherichia coli. After purification
      to homogeneity, the protein was evaluated for allergenicity and its ability to
      induce blocking antibodies upon immunization. RESULTS: Upon immunization of mice,
      DpTTDp induced high levels of protective IgG-antibodies that blocked allergic
      patients' IgE reactivity to HDM. In addition, DpTTDp lacked relevant IgE
      reactivity, induced low T-cell proliferation and IFN-gamma in peripheral blood
      mononuclear cells of HDM-allergic patients' sera. CONCLUSION: The protein
      represents a promising HDM-allergy immunotherapy candidate vaccine.

PMID- 29569513
TI  - A Role for the Frontal Aslant Tract in Speech Planning: A Neurosurgical Case
      Study.
AB  - Frontal and temporal white matter pathways play key roles in language processing,
      but the specific computations supported by different tracts remain a matter of
      study. A role in speech planning has been proposed for a recently described
      pathway, the frontal aslant tract (FAT), which connects the posterior inferior
      frontal gyrus to the pre-SMA. Here, we use longitudinal functional and structural
      MRI and behavioral testing to evaluate the behavioral consequences of a lesion to
      the left FAT that was incurred during surgical resection of a frontal glioma in a
      60-year-old woman, Patient AF. The pattern of performance in AF is compared,
      using the same measures, with that in a 37-year-old individual who underwent a
      left anterior temporal resection and hippocampectomy (Patient AG). AF and AG were
      both cognitively intact preoperatively but exhibited specific and doubly
      dissociable behavioral deficits postoperatively: AF had dysfluent speech but no
      word finding difficulty, whereas AG had word finding difficulty but otherwise
      fluent speech. Probabilistic tractography showed that the left FAT was lesioned
      postoperatively in AF (but not AG) whereas the inferior longitudinal fasciculus
      was lesioned in AG (but not AF). Those structural changes were supported by
      corresponding changes in functional connectivity to the posterior inferior
      frontal gyrus: decreased functional connectivity postoperatively between the
      posterior inferior frontal gyrus and pre-SMA in AF (but not AG) and decreased
      functional connectivity between the posterior inferior frontal gyrus and the
      middle temporal gyrus in AG (but not AF). We suggest from these findings that the
      left FAT serves as a key communicative link between sentence planning and lexical
      access processes.

PMID- 29569514
TI  - Expression levels of selected genes can predict individual rheumatoid arthritis
      patient response to tumor necrosis factor alpha blocker treatment.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) patients have many therapeutic options;
      however, tools to predict individual patient response are limited. The Genefron
      personal diagnostic kit, developed by analyzing large datasets, utilizes selected
      interferon stimulated gene expressions to predict treatment response. This study
      evaluates the kit's prediction accuracy of individual RA patients' response to
      tumor necrosis alpha (TNFalpha) blockers. METHODS: A retrospective analysis was
      performed on RA patients reported in published datasets. A prospective analysis
      assessed RA patients, before and 3 months after starting a TNFalpha blocker.
      Clinical response was evaluated according to EULAR response criteria. Blood
      samples were obtained before starting treatment and were analyzed utilizing the
      kit which measures expression levels of selected genes by quantitative real time
      polymerase chain reaction (PCR). ROC analysis was applied to the published
      datasets and the prospective data. RESULTS: The Genefron kit analysis of
      retrospective data predicted the response to a TNFalpha blocker in 53 of 61 RA
      patients (86.8% accuracy). In the prospective analysis, the kit predicted the
      response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response,
      and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC
      analysis applied to the two published datasets yielded an AUC of 0.89. ROC
      analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity -
      100%, specificity - 75%) The statistical power obtained in the prospective study
      was .9. CONCLUSION: The diagnostic kit predicted the response to TNFalpha
      blockers in a high percentage of patients assessed retrospectively or
      prospectively. This personal kit may guide selection of a suitable biological
      drug for the individual RA patient.

PMID- 29569515
TI  - Prevalence of salivary human herpesviruses in pediatric multiple sclerosis cases
      and controls.
AB  - BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of unknown
      origin. The current paradigm is that disease develops in genetically susceptible
      individuals, influenced by environmental factors. Epstein-Barr virus (EBV) and
      human herpesvirus 6 (HHV-6) have particularly strong associations with the
      disease. Both viruses are typically acquired during childhood, decades before MS
      presents. However, in patients with pediatric MS, the temporal window between
      viral acquisition and disease onset is shortened, which may provide insights into
      the association of herpesviruses with MS. OBJECTIVE: To compare the frequency of
      EBV and HHV-6 in the saliva of a cohort of pediatric MS patients and age-matched
      controls. METHODS: The study enrolled 32 pediatric MS patients and 42 controls
      and evaluated saliva for HHV-6 u57 and EBV lmp-1 amplification by droplet digital
      polymerase chain reaction (ddPCR). RESULTS: Pediatric MS patients did not differ
      from controls in the frequency or magnitude of salivary viral shedding. During
      the assessment of EBV positivity, distinct profiles emerged that correlated with
      target amplicon mutations. CONCLUSIONS: None of these mutations were evident in
      EBV-positive samples from pediatric MS patients, whereas they were present in
      pediatric controls, in addition to MS and control adults, suggesting differential
      host-immune control of EBV in this pediatric MS cohort.

PMID- 29569516
TI  - Intravascular Large B-Cell Lymphoma Within a Thyroid Nodule: A Diagnostic
      Pitfall.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large B-cell
      lymphoma, where the neoplastic lymphoid proliferation resides predominantly
      within the lumens of blood vessels but with no or few circulating neoplastic
      cells in the peripheral circulation. Focal or subtle involvement in some cases
      can cause the diagnosis to be misinterpreted or even overlooked, delaying the
      initiation of appropriate treatment. Our report focuses on a 78-year-old woman
      with a progressively enlarging thyroid mass, verified by ultrasound. She
      underwent a hemithyroidectomy, and microscopic evaluation demonstrated nodular
      thyroid parenchyma with atypical large cells in an intravascular distribution
      pattern identified on high magnification. Thorough evaluation showed that the
      large intravascular cells were positive CD20, PAX-5, and Ki-67 by
      immunoperoxidase staining, which lead to the diagnosis of IVLBCL. This case
      emphasizes the subtle appearance of IVLBCL, which may be missed on low-power
      light microscopy, and the need for careful evaluation of thyroid resection
      specimens.

PMID- 29569517
TI  - Discrepancies between crystallized and fluid ability are associated with
      frequency of social and physical engagement in community dwelling older adults.
AB  - OBJECTIVE: Age differences have been noted in the discrepancies between
      crystallized and fluid ability (Gc-Gf). Larger Gc-Gf discrepancies have also been
      shown to be associated with Alzheimer's disease biomarkers and clinical severity.
      However, little is known regarding the relationship between Gc-Gf discrepancies
      in normal aging and functional outcomes. The aim of the present study was to
      examine this. METHOD: Data from 104 adults (Mage = 71.70 years, SD = 9.016) were
      included in the present study. Measures from the NIH toolbox were used to form
      the discrepancy scores. Physical, cognitive, and social activities were
      identified using the Community Healthy Activities Model Program for Seniors
      activity questionnaire. Linear regression analyses, controlling for age,
      education, gender, health, and depressive symptoms, were used to examine the
      association between social, cognitive, and physical activities on Gc-Gf
      discrepancies. RESULTS: Results showed that social and physical activity were
      significantly associated with greater discrepancies between crystallized and
      fluid ability, independent of covariates. There was no association between
      cognitive activity and Gc-Gf discrepancies. CONCLUSIONS: Larger discrepancies
      between crystallized and fluid ability are related to frequency of social and
      physical activity. The findings support previous research that discrepancy scores
      may serve as a marker of cognitive decline. In more highly educated older
      individuals, Gc-Gf discrepancies may be a more accurate indicator of actual
      cognitive status.

PMID- 29569518
TI  - Do selective serotonin reuptake inhibitors increase the risk of bleeding or
      mortality following coronary artery bypass graft surgery? A meta-analysis of
      observational studies.
AB  - INTRODUCTION: Depressive illness has a high prevalence in patients undergoing
      coronary artery bypass graft surgery (CABG). The first line treatment for
      depression are selective serotonin reuptake inhibitors (SSRIs) which inhibit
      serotonin reuptake in the presynaptic neuronal membrane and uptake by platelets,
      inhibiting subsequent serotonin-mediated platelet activation. This presents a
      theoretically increased risk of bleeding and subsequent postoperative mortality.
      This review aims to investigate the effects of SSRIs on postoperative bleeding,
      defined as the need for transfusions and re-operation for bleeding, as well as 30
      day mortality in patients undergoing CABG. METHOD: Four hundred and thirty-seven
      papers were screened with seven meeting the full inclusion criteria. RESULTS:
      Meta-analysis demonstrated that SSRI use increased the risk of red blood cell
      transfusion (odds ratio (OR) = 1.15; 95% confidence interval (CI): 1.06-1.26),
      but resulted in no difference in the rate of re-operation for bleeding (OR =
      1.07; 95% CI: 0.66-1.74). SSRI use had no effect on the rates of platelet (OR =
      0.93; 95% CI: 0.79-1.09) or fresh frozen plasma (OR = 0.96; 95% CI: 0.74-1.24)
      transfusion nor on the mortality rate (OR =1.03; 95 CI: 0.90-1.17). CONCLUSION:
      This review demonstrates that SSRIs are largely safe in cardiac surgery as no
      increase in mortality was observed. However, there is a significantly raised
      chance of red blood cell transfusion. The heterogeneous nature of the current
      evidence base highlights the need for further research into SSRIs and whether any
      effect on patient outcomes in cardiac surgery occurs.

PMID- 29569519
TI  - Idiopathic pericardial cyst causing heart failure.

PMID- 29569520
TI  - Advance Care Planning in Chinese Seniors: Cultural Perspectives.
AB  - In traditional Chinese culture, death was sensitive and mentioning it was
      sacrilegious and to be avoided. Many Chinese families object to telling the
      patient a "bad" diagnosis or prognosis, which may hinder the chance in advance
      care planning (ACP) discussion. While death remains an inevitable consequence of
      being born, as such, it is important that human beings recognize its
      inevitability and plan ahead of a good death. Advance care planning enables
      patients to assert their care preferences in the event that they are unable to
      make their own medical decisions. In China, a rapidly aging demographic presents
      additional challenges to quality end-of-life care. The adoption of palliative
      care in China has been slow, with a curative approach dominating health-care
      strategies. In this article, we would summarize China's current situation in
      population aging, palliative care development, and Chinese cultural values on
      death and dying and review the advance directive and end-of-life care preferences
      among Chinese elderly patients. Current literature recommended the use of
      indirect communication approaches to determine Chinese seniors' readiness. In
      individual practice, using depersonalized communication strategies to initiate
      the discussion was recommended to determine older Chinese seniors' readiness.

PMID- 29569521
TI  - Impact of SCBA size and fatigue from different firefighting work cycles on
      firefighter gait.
AB  - Risk of slips, trips and falls in firefighters maybe influenced by the
      firefighter's equipment and duration of firefighting. This study examined the
      impact of a four self-contained breathing apparatus (SCBA) three SCBA of
      increasing size and a prototype design and three work cycles one bout (1B), two
      bouts with a five-minute break (2B) and two bouts back-to-back (BB) on gait in 30
      firefighters. Five gait parameters (double support time, single support time,
      stride length, step width and stride velocity) were examined pre- and post
      firefighting activity. The two largest SCBA resulted in longer double support
      times relative to the smallest SCBA. Multiple bouts of firefighting activity
      resulted in increased single and double support time and decreased stride length,
      step width and stride velocity. These results suggest that with larger SCBA or
      longer durations of activity, firefighters may adopt more conservative gait
      patterns to minimise fall risk. Practitioner Summary: The effects of four self
      contained breathing apparatus (SCBA) and three work cycles on five gait
      parameters were examined pre- and post-firefighting activity. Both SCBA size and
      work cycle affected gait. The two largest SCBA resulted in longer double support
      times. Multiple bouts of activity resulted in more conservative gait patterns.

PMID- 29569522
TI  - Can athletes' reports of self-regulated learning distinguish deliberate practice
      from physical preparation activity?
AB  - Sustained persistence in deliberate practice (DP) could be aided by engagement in
      adaptive motivational and metacognitive types of self-regulated learning (SRL)
      processes. We examined relationships between SRL and each of DP and physical
      preparation (PP; e.g., cross-training) in supervised, unsupervised, social and
      non-social practice contexts. 272 individual-sport athletes (from city to
      international level; M sport activity = 13.54 hrs/wk; 200 males, ages 18-35)
      completed the Self-Regulation of Learning Self-Report Scale and reported weekly
      DP and PP amounts. We found contrasting results depending on specific SRL
      processes. Self-monitoring was related to DP (total, supervised, social
      conditions) but inversely related to PP. Effort was inversely related to
      supervised DP but positively associated with PP. Planning was associated with DP,
      and reflection and self-efficacy related to PP. We discuss the contrast between
      DP and PP, highlighting differences in the nature of these practice activities,
      and self-monitoring as a key SRL process for DP.

PMID- 29569523
TI  - Reply to Behrman.

PMID- 29569524
TI  - Risk factors of cerebral microbleeds in young and middle-aged patients with
      hypertension.
AB  - Objective This study aimed to investigate the incidence and related risk factors
      of cerebral microbleeds (CMBs) in young and middle-aged patients with
      hypertension. Methods The study included 232 young and middle-aged (18-59 years
      old) patients with hypertension from September 2014 to December 2016 in the
      Department of Neurology, Affiliated Hospital of Guizhou Medical University,
      China. The data were recorded which included demographics, vascular risk factors,
      medication history, and imaging data of patients. CMBs were evaluated based on
      the microbleeds anatomical rating scale. Results Of the enrolled participants,
      115 were CMB positive, accounting for 49.6%. CMBs were more prone to occur in
      deep regions than in others (39.13%). Multiple cerebral microbleeds were
      associated with white matter hyperintensities(WMH), dyslipidemia,
      hyperhomocysteine, and uric acid. Moreover, WMH, dyslipidemia, ever smoker,
      antiplatelets use, and hyperhomocysteine were found to be risk factors for deep
      or infratentorial CMBs in young and middle-aged patients with hypertension.
      However, the lobar CMBs only had an independent correlation with dyslipidemia in
      these participants. Conclusions The incidence of CMBs in patients with
      hypertension was relatively high. It mostly occurred in a deep or infratentorial
      area with more vascular-associated risk factors. However, in patients with lobar
      CMBs, factors associated with lipid metabolism, such as amyloid deposition and
      unidentified genotype variation, may be crucial. Screening and regular follow-ups
      of CMBs by Susceptibility Weighted Imaging and active prevention in young and
      middle-aged patients with hypertension have clinical significance for timely
      understanding and predicting the occurrence and development of related
      cerebrovascular disease events.

PMID- 29569525
TI  - Prevalence and trends of overweight and obesity in older adults from 10 European
      countries from 2005 to 2013.
AB  - AIMS: Overweight and obesity are clinical public-health concerns worldwide.
      Amongst older adults, the prevalence of overweight and obesity is considered
      high. The purpose of this study was to provide current data regarding the
      prevalence and trends of overweight and obesity of adults from 2005 to 2013 in 10
      European countries. METHODS: The data used in the present study were derived from
      the first, second, fourth and fifth waves of the Survey of Health, Ageing and
      Retirement in Europe. The present study includes individuals aged ?50 years from
      10 European countries. Body mass index (BMI) was calculated from self-reported
      height and weight (kg/m2). RESULTS: The general prevalence of overweight (BMI ?25
      kg/m2) was slightly above 60% and remained stable between 2005 (60.1%, 95%
      confidence interval (CI): 59.3-60.9%) and 2013 (60.3%, 95% CI: 59.7-60.9%). On
      the other hand, the prevalence of obesity (BMI ?30 kg/m2) increased significantly
      (1.6 points, 95% CI: 0.7-2.6) from 17.5% in 2005 to 19.2% in 2013. Although the
      prevalence of obesity increased in most countries, the only significant increase
      was observed in Germany (5.8 points, 95% CI: 1.8-9.9). Spain was the only country
      where the prevalence of obesity decreased significantly (-4.7 points, 95% CI: 
      8.8 to -0.5). Sex and age differences are reported. CONCLUSIONS: Although the
      prevalence of overweight was stable, the prevalence of obesity rose. Based on the
      data currently available for Europe, the prevalence of obesity in European older
      adults has already reached epidemic proportions, which reinforces the need for
      the development of effective healthy lifestyle programs.

PMID- 29569527
TI  - Future directions in pharmacogenomics discovery in cardiovascular disease.

PMID- 29569526
TI  - Pharmacogenetics and the treatment of chronic myeloid leukemia: how relevant
      clinically? An update.
AB  - Despite the excellent efficacy and improved clinical responses obtained with
      imatinib mesylate (IM), development of resistance in a significant proportion of
      chronic myeloid leukemia (CML) patients on IM therapy have emerged as a
      challenging problem in clinical practice. Resistance to imatinib can be due to
      heterogeneous array of factors involving BCR/ABL-dependent and BCR/ABL
      independent pathways. Although BCR/ABL mutation is the major contributory factor
      for IM resistance, reduced bio-availability of IM in leukemic cells is also an
      important pharmacokinetic factor that contributes to development of resistance to
      IM in CML patients. The contribution of polymorphisms of the pharmacogenes in
      relation to IM disposition and treatment outcomes have been studied by various
      research groups in numerous population cohorts. However, the conclusions arising
      from these studies have been highly inconsistent. This review encompasses an
      updated insight into the impact of pharmacogenetic variability on treatment
      response of IM in CML patients.

PMID- 29569528
TI  - Capacity building for health inequality monitoring in Indonesia: enhancing the
      equity orientation of country health information system.
AB  - BACKGROUND: Inequalities in health represent a major problem in many countries,
      including Indonesia. Addressing health inequality is a central component of the
      Sustainable Development Goals and a priority of the World Health Organization
      (WHO). WHO provides technical support for health inequality monitoring among its
      member states. Following a capacity-building workshop in the WHO South-East Asia
      Region in 2014, Indonesia expressed interest in incorporating health-inequality
      monitoring into its national health information system. OBJECTIVES: This article
      details the capacity-building process for national health inequality monitoring
      in Indonesia, discusses successes and challenges, and how this process may be
      adapted and implemented in other countries/settings. METHODS: We outline key
      capacity-building activities undertaken between April 2016 and December 2017 in
      Indonesia and present the four key outcomes of this process. RESULTS: The
      capacity-building process entailed a series of workshops, meetings, activities,
      and processes undertaken between April 2016 and December 2017. At each stage, a
      range of stakeholders with access to the relevant data and capacity for data
      analysis, interpretation and reporting was engaged with, under the stewardship of
      state agencies. Key steps to strengthening health inequality monitoring included
      capacity building in (1) identification of the health topics/areas of interest,
      (2) mapping data sources and identifying gaps, (3) conducting equity analyses
      using raw datasets, and (4) interpreting and reporting inequality results. As a
      result, Indonesia developed its first national report on the state of health
      inequality. A number of peer-reviewed manuscripts on various aspects of health
      inequality in Indonesia have also been developed. CONCLUSIONS: The capacity
      building process undertaken in Indonesia is designed to be adaptable to other
      contexts. Capacity building for health inequality monitoring among countries is a
      critical step for strengthening equity-oriented national health information
      systems and eventually tackling health inequities.

PMID- 29569529
TI  - Applying the Innov8 approach for reviewing national health programmes to leave no
      one behind: lessons learnt from Indonesia.
AB  - The World Health Organization's Innov8 Approach for Reviewing National Health
      Programmes to Leave No One Behind is an eight-step process that supports the
      operationalization of the Sustainable Development Goals' commitment to 'leave no
      one behind'. In 2014-2015, Innov8 was adapted and applied in Indonesia to review
      how the national neonatal and maternal health action plans could become more
      equity-oriented, rights-based and gender-responsive, and better address critical
      social determinants of health. The process was led by the Indonesian Ministry of
      Health, with the support of WHO. It involved a wide range of actors and aligned
      with/fed into the drafting of the maternal newborn health action plan and the
      implementation planning of the newborn action plan. Key activities included a
      sensitization meeting, diagnostic checklist, review workshop and in-country work
      by the review teams. This 'methods forum' article describes this adaptation and
      application process, the outcomes and lessons learnt. In conjunction with other
      sources, Innov8 findings and recommendations informed national and sub-national
      maternal and neonatal action plans and programming to strengthen a 'leave no one
      behind' approach. As follow-up during 2015-2017, components of the Innov8
      methodology were integrated into district-level planning processes for maternal
      and newborn health, and Innov8 helped generate demand for health inequality
      monitoring and its use in planning. In Indonesia, Innov8 enhanced national
      capacity for equity-oriented, rights-based and gender-responsive approaches and
      addressing critical social determinants of health. Adaptation for the national
      planning context (e.g. decentralized structure) and linking with health
      inequality monitoring capacity building were important lessons learnt. The pilot
      of Innov8 in Indonesia suggests that this approach can help operationalize the
      SDGs' commitment to leave no one behind, in particular in relation to influencing
      programming and monitoring and evaluation.

PMID- 29569530
TI  - Frontiers in biomedical polymers conference series.

PMID- 29569531
TI  - 12th FBPS2017, KIST, Seoul.

PMID- 29569532
TI  - The relationship between self-efficacy and transition to work or studies in young
      adults with disabilities.
AB  - AIM: To investigate perceived self-efficacy in unemployed young adults with
      disabilities, and the association between self-efficacy and transition to work or
      studies. METHODS: This prospective cohort study collected data through self
      report questionnaires and registry data from a vocational rehabilitation project
      with young adults, aged 19-29 years. The Swedish Social Insurance Agency, the
      Swedish Public Employment Service and the participating municipalities identified
      potential participants for the study. A total of 531 participants were included
      in the study, of which 249 (47%) were available for analysis. Multinomial
      logistic regression models were carried out to estimate the associations between
      self-efficacy, demographic (age, country of birth, education level), health and
      employment status. The latter was coded as: 'no transition to work or studies',
      'transition to studies', and 'transition to work'. RESULTS: A higher level of
      self-efficacy was associated with increased odds for 'transition to work' (OR =
      2.37, p < 0.05). This finding remained consistent when adjusting for possible
      confounders. The mean value of self-efficacy was low, and participants with lower
      self-efficacy reported worse self-rated health ( p < 0.001) compared to
      participants with higher self-efficacy. CONCLUSIONS: The results from this study
      suggest that self-efficacy should be addressed in the vocational rehabilitation
      of young adults with disabilities in order to support their transition and
      integration into the labour market.

PMID- 29569533
TI  - How social media is transforming the spreading of knowledge: Implications for our
      perceptions concerning vaccinations and migrant health.

PMID- 29569534
TI  - Competency in Acute Resuscitation Through Successive Simulation (CARTSS): a
      mentor based, near-peer learning initiative.

PMID- 29569535
TI  - Changing to a vegetarian diet reduces the body creatine pool in omnivorous women,
      but appears not to affect carnitine and carnosine homeostasis: a randomised
      trial.
AB  - Balanced vegetarian diets are popular, although they are nearly absent in
      creatine and carnosine and contain considerably less carnitine than non
      vegetarian diets. Few longitudinal intervention studies investigating the effect
      of a vegetarian diet on the availability of these compounds currently exist. We
      aimed to investigate the effect of transiently switching omnivores onto a
      vegetarian diet for 6 months on muscle and plasma creatine, carnitine and
      carnosine homeostasis. In a 6-month intervention, forty omnivorous women were
      ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian
      diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with
      daily beta-alanine (0.8-0.4 g/d) and creatine supplementation (1 g creatine
      monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and
      6 months (6M), a fasted venous blood sample and 24-h urine was collected, and
      muscle carnosine content was determined by proton magnetic resonance spectroscopy
      (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle
      total creatine content declined from 0M to 3M in Veg+Pla (P=0.013 and P=0.009,
      respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0.004).
      None of the carnitine-related compounds in plasma or muscle showed a significant
      time*group interaction effect. 1H-MRS-determined muscle carnosine content was
      unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus
      (P<0.001) and gastrocnemius (P=0.001) muscle. To conclude, the body creatine pool
      declined over a 3-month vegetarian diet in omnivorous women, which was
      ameliorated when accompanied by low-dose dietary creatine supplementation.
      Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian
      diet, respectively.

PMID- 29569536
TI  - Introduction of iodised salt benefits infants' mental development in a community
      based cluster-randomised effectiveness trial in Ethiopia.
AB  - The effectiveness of salt iodisation in improving the mental development of young
      children has not been assessed. We implemented a community-based cluster
      randomised effectiveness trial in sixty randomly selected districts in the Amhara
      region of Ethiopia. We randomly allocated each district to treatment and randomly
      selected one of its villages. In parallel to national salt iodisation efforts,
      iodised salt was brought early into the markets of the thirty intervention
      villages before it became widely available in the thirty control villages 4-6
      months later. The primary outcome was children's mental development scores on the
      Bayley Scales. This was an intention-to-treat analysis using mixed linear models
      adjusted for covariates and clusters. The trial was registered at
      ClinicalTrials.gov, NCT013496. We assessed 1835 infants aged 5-11 months at
      baseline. The same children (85 % of the sample) were re-assessed at 20-29 months
      when all villages had iodised salt. At endline, urinary iodine concentration was
      higher in children in the intervention group compared with those in the control
      group (median 228.0 v. 155.1 ug/l, P=0.001). The intervention group had higher
      scores compared with the control group on the Bayley composite score (raw
      scores:130.60 v. 128.51; standardised scores: 27.8 v. 26.9; d=0.13; 95 % CI 0.02,
      0.23) and three of the four subscales: cognitive (53.27 v. 52.54, d=0.13; 95 % CI
      0.03, 0.23), receptive language (20.71 v. 20.18, d=0.13; 95 % CI 0.03, 0.24) and
      fine motor (35.45 v. 34.94, d=0.15; 95 % CI 0.04, 0.25). The introduction of
      iodised salt contributes to children's higher urinary iodine concentration and
      mental development.

PMID- 29569537
TI  - A preclinical study to model taurine pharmokinetics in the undernourished rat.
AB  - Malnutrition is a common feature of chronic and acute diseases, often associated
      with a poor prognosis, including worsening of clinical outcome, owing, among
      other factors, to dysfunction of the most internal organs and systems affecting
      the absorption, metabolism and elimination of drugs and nutrients. Taurine is
      involved in numerous biological processes and is required in increased amounts in
      response to pathological conditions. The aim of this study was to describe the
      behaviour of taurine in well-nourished (WN) rats and to analyse the influence of
      protein-energy undernutrition on the pharmacokinetic (PK) parameters of taurine,
      using a PK model. Wistar rats were randomly distributed into two groups, WN and
      undernourished (UN), and taurine was administered intravenously or orally at
      different doses: 1, 10 and 100 mg. Population pharmacokinetic modelling of plasma
      levels was performed using the NONMEM 7.2 program. Several distribution and
      absorption models were explored in combination with dose and/or time covariate
      effects. Covariates such as nutritional status, serum albumin, body weight and
      score of undernutrition were used. A two-compartment population pharmacokinetic
      model with zero-order endogenous formation, passive absorption, first-order
      kinetics distribution and non-linear elimination with parallel Michaelis-Menten
      excretion and reabsorption processes best described taurine pharmacokinetics.
      Undernutrition acted as a covariate reducing the V max of the active elimination
      process. Data analysis showed linear absorption and distribution, and non-linear
      elimination processes for taurine. Elimination of taurine was reduced in UN
      animals, suggesting that the reabsorption process via the secretion transporter
      was modified in that group.

PMID- 29569538
TI  - Serum metabolomics study of nutrient metabolic variations in chronic heat
      stressed broilers.
AB  - To investigate the effects of heat stress on broiler metabolism, we assigned 144
      broilers to normal control (NC), heat stress (HS) or pair-fed (PF) groups and
      then monitored the effects using growth performance, carcass characteristics,
      biochemical assays and GC-MS-based metabolomics. The up-regulation of cloacal
      temperature confirmed that our experiment was successful in inducing chronic heat
      stress. The average daily gain and average daily feed intake of the HS group were
      significantly lower than those of the NC group, by 28.76 and 18.42 %,
      respectively (P1 and P<0.05). The greater feed:gain ratio of the HS group was
      significantly positively correlated with the leg, abdominal fat, subcutaneous fat
      and intramuscular fat proportions and levels of some free amino acids (proline, l
      cysteine, methionine and threonine) but was negatively correlated with breast
      proportion and levels of some NEFA (stearic acid, arachidonic acid, palmitic acid
      and oleic acid). These findings indicated that the heat-stressed broilers were in
      negative energy balance and unable to effectively mobilise fat, thereby resulting
      in protein decomposition, which subsequently affected growth performance and
      carcass characteristics.

PMID- 29569539
TI  - Postprandial glycaemic and lipaemic responses to chronic coffee consumption may
      be modulated by CYP1A2 polymorphisms.
AB  - There is much epidemiological evidence suggesting a reduced risk of development
      of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have
      been few longer-term interventions, directly examining the effects of coffee
      intake on glucose and lipid metabolism. Previous studies may be confounded by
      inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP
      in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with
      carriers of the C allele considered to be of a 'slow' metaboliser phenotype. This
      study investigated the effects of regular coffee intake on markers of glucose and
      lipid metabolism in coffee-naive individuals, with novel analysis by rs762551
      genotype. Participants were randomised to either a coffee group (n 19) who
      consumed four cups/d instant coffee for 12 weeks or a control group (n 8) who
      remained coffee/caffeine free. Venous blood samples were taken pre- and post
      intervention. Primary analysis revealed no significant differences between
      groups. Analysis of the coffee group by genotype revealed several differences.
      Before coffee intake, the AC genotype ('slow' caffeine metabolisers, n 9)
      displayed higher baseline glucose and NEFA than the AA genotype ('fast' caffeine
      metabolisers, n 10, P<0.05). Post-intervention, reduced postprandial glycaemia
      and reduced NEFA suppression were observed in the AC genotype, with the opposite
      result observed in the AA genotype (P<0.05). These observed differences between
      genotypes warrant further investigation and indicate there may be no one-size
      fits-all recommendation with regard to coffee drinking and T2D risk.

PMID- 29569540
TI  - Leucine promotes differentiation of porcine myoblasts through the protein kinase
      B (Akt)/Forkhead box O1 signalling pathway.
AB  - Leucine, one of the branched-chain amino acids, is the only amino acid to
      regulate protein turnover in skeletal muscle. Leucine not only increases muscle
      protein synthesis, but also decreases muscle protein degradation. It is well
      documented that leucine plays a positive role in differentiation of murine muscle
      cells. However, the role of leucine on porcine myoblast differentiation and its
      mechanism remains unclear. In this study, porcine myoblasts were induced to
      differentiate with differentiation medium containing different concentrations of
      leucine, and wortmannin was used to interdict the activity of protein kinase B
      (Akt). We found that leucine increased the number of myosin heavy chain-positive
      cells and creatine kinase activity. Moreover, leucine increased the mRNA and
      protein levels of myogenin and myogenic determining factor (MyoD). In addition,
      leucine increased the levels of phosphorylated Akt/Akt and phosphorylated
      Forkhead box O1 (P-FoxO1)/FoxO1, as well as decreased the protein level of FoxO1.
      However, wortmannin, a specific repressor of PI3K/Akt signalling pathway,
      attenuated the positive role of leucine on porcine myoblast differentiation. Our
      results suggest that leucine promotes porcine myoblast differentiation through
      the Akt/FoxO1 signalling pathway.

PMID- 29569541
TI  - Energy efficiency of digestible protein, fat and carbohydrate utilisation for
      growth in rainbow trout and Nile tilapia.
AB  - Currently, energy evaluation of fish feeds is performed on a digestible energy
      basis. In contrast to net energy (NE) evaluation systems, digestible energy
      evaluation systems do not differentiate between the different types of digested
      nutrients regarding their potential for growth. The aim was to develop an NE
      evaluation for fish by estimating the energy efficiency of digestible nutrients
      (protein, fat and carbohydrates) and to assess whether these efficiencies
      differed between Nile tilapia and rainbow trout. Two data sets were constructed.
      The tilapia and rainbow data set contained, respectively, eight and nine
      experiments in which the digestibility of protein, fat and energy and the
      complete energy balances for twenty-three and forty-five diets was measured. The
      digestible protein (dCP), digestible fat (dFat) and digestible carbohydrate
      intakes (dCarb) were calculated. By multiple regression analysis, retained energy
      (RE) was related to dCP, dFat and dCarb. In tilapia, all digestible nutrients
      were linearly related to RE (P<0.001). In trout, RE was quadratically related to
      dCarb (P<0.01) and linearly to dCP and dFat (P<0.001). The NE formula was
      NE=11.5*dCP+35.8*dFAT+11.3*dCarb for tilapia and NE=13.5*dCP+33.0*dFAT+34.0*dCarb
      3.64*(dCarb)2 for trout (NE in kJ/(kg0.8*d); dCP, dFat and dCarb in g/(kg0.8*d)).
      In tilapia, the energetic efficiency of dCP, dFat and dCarb was 49, 91 and 66 %,
      respectively, showing large similarity with pigs. Tilapia and trout had similar
      energy efficiencies of dCP (49 v. 57 %) and dFat (91 v. 84 %), but differed
      regarding dCarb.

PMID- 29569542
TI  - Innate differences and colostrum-induced alterations of jejunal mucosal proteins
      in piglets with intra-uterine growth restriction.
AB  - Mammalian neonates undergo rapid transitions from a sterile uterine environment
      with a continuous intravenous supply of nutrients to a microbe-rich environment
      with intermittent ingesting of colostrum/milk via the gut. Currently, little is
      known about the colostrum-induced alterations of intestinal mucosal proteins in
      piglets with intra-uterine growth restriction (IUGR). In this study, we sought to
      investigate the innate differences and effects of colostrum on alterations in
      small-intestinal proteomes of IUGR piglets. Two IUGR (approximately 0.9 kg) and
      two normal-birth weight (NBW; approximately 1.3 kg) piglets were obtained from
      each of six sows at birth. One half (n 12; 6 IUGR v. 6 NBW) of the selected
      newborn piglets were killed to obtain jejunum samples, and the other half (n 12;
      6 IUGR v. 6 NBW) of the newborn piglets were allowed to suckle colostrum from
      their own mothers for 24 h before jejunum sample collection. On the basis of
      proteomic analysis, we identified thirty-one differentially expressed proteins in
      the jejunal mucosa between IUGR and normal neonates before or after colostrum
      consumption. The intestinal proteins altered by colostrum feeding play important
      roles in the following: (1) increasing intestinal integrity, transport of
      nutrients, energy metabolism, protein synthesis, immune response and, therefore,
      cell proliferation; and (2) decreasing oxidative stress, and therefore cell
      apoptosis, in IUGR neonates. However, colostrum only partially ameliorated the
      inferior status of the jejunal mucosa in IUGR neonates. These findings provide
      the first evidence in intestinal protein alterations of IUGR neonates in response
      to colostrum ingestion, and thus render new insights into the mechanisms
      responsible for impaired growth in IUGR neonates and into new nutritional
      intervention strategies.

PMID- 29569543
TI  - Effect of nutritional supplement on bone marrow-derived mesenchymal stem cells
      from aplastic anaemia.
AB  - Aplastic anaemia (AA) is characterised by pancytopenia resulting from a marked
      reduction in haemopoietic stem cells (HSC). The regulation of haemopoiesis
      depends on the interaction between HSC and various cells of the bone marrow (BM)
      microenvironment, including BM-derived mesenchymal stromal cells (BMSC). The
      purpose of this study was to analyse the biological effect of nutritional
      supplement (NS), a dietary supplement consisting of thirty-six compounds: amino
      acids, nucleotides, vitamins and micronutrients on the BMSC of AA rats. The AA
      rat model was established by irradiating X-ray (2.5 Gy) and intraperitoneal
      injections of cyclophosphamide (35 mg/kg; Sigma) and chloramphenicol (35 mg/kg;
      Sigma). Then AA rats were fed with NS in a dose-dependent manner (2266.95,
      1511.3, 1057.91 mg/kg d) by intragastric administration. The effect of NS on the
      BMSC of AA rats was analysed. As compared with AA rats, NS treatment
      significantly improved these peripheral blood parameters and stimulated the
      proliferation of total femoral nucleated cells. NS treatment affected
      proliferative behaviour of BMSC and suppressed BMSC differentiation to
      adipocytes. Furthermore, NS treatment of AA rats accelerated osteogenic
      differentiation of BMSC and enhanced bone mineral density. Co-incubation of HSC
      with mesenchymal stromal cells and serum from AA rats subjected to high-dose NS
      markedly improved the yield of CD34+cells. Protein microarray analysis revealed
      that there were eleven differentially expressed proteins in the NS group compared
      with the AA rat group. The identified specific NS might be implicated in
      rehabilitation of BMSC in AA rats, suggesting their potential of nutritional
      support in AA treatment.

PMID- 29569544
TI  - A comparison between two healthy diet scores, the modified Mediterranean diet
      score and the Healthy Nordic Food Index, in relation to all-cause and cause
      specific mortality.
AB  - High adherence to healthy diets has the potential to prevent disease and prolong
      life span, and healthy dietary pattern scores have each been associated with
      disease and mortality. We studied two commonly promoted healthy diet scores
      (modified Mediterranean diet score (mMED) and the Healthy Nordic Food Index
      (HNFI)) and the combined effect of the two scores in association with all-cause
      and cause-specific mortality (cancer, CVD and ischaemic heart disease). The study
      included 38 428 women (median age of 61 years) from the Swedish Mammography
      Cohort. Diet and covariate data were collected in a questionnaire. mMED and HNFI
      were generated and categorised into low-, medium- and high-adherence groups, and
      in nine combinations of these. Multivariable-adjusted hazard ratios (HR) of
      register-ascertained mortality and 95 % CI were calculated in Cox proportional
      hazards regression analysis. During follow-up (median: 17 years), 10 478 women
      died. In the high-adherence categories compared with low-adherence categories,
      the HR for all-cause mortality was 0.76 (95 % CI 0.70, 0.81) for mMED and 0.89
      (95 % CI 0.83, 0.96) for HNFI. Higher adherence to mMED was associated with lower
      mortality in each stratum of HNFI in the combined analysis. In general, mMED,
      compared with HNFI, was more strongly associated with a lower cause-specific
      mortality. In Swedish women, both mMED and HNFI were inversely associated with
      all-cause and cardiovascular mortality. The combined analysis, however, indicated
      an advantage to be adherent to the mMED. The present version of HNFI did not
      associate with mortality independent of mMED score.

PMID- 29569545
TI  - The potential of flow-through microdialysis for probing low-molecular weight
      organic anions in rhizosphere soil solution.
AB  - In this paper, flow-through microdialysis is presented as a novel analytical tool
      for automatic sampling of low molecular weight organic anions (LMWOA), such as
      oxalate and citrate, in solid samples of environmental concern. The microsampling
      methodology involves the implantation of dedicated capillary-type probes offering
      unrivalled spatial resolution (ca. 200MUm) in definite soil sites. These passive
      samplers are aimed at monitoring local processes, such as the release of organic
      acids occurring in the rhizosphere environment, in nearly real-time. The
      influence of chemical and physical variables (composition and flow rate of the
      perfusion liquid, ionic strength and pH of the outer medium and presence of metal
      ions therein) was assessed in vitro using liquid-phase assays. On the other hand,
      the resistance of the external solid medium to mass transfer, and the actual
      applicability of in vivo calibration methods were investigated using quartz sand
      as an inert model soil. Microdialysers furnished with 3cm long semipermeable
      tubular membranes were perfused with 0.01M NaNO3 at a flow rate of 2.0MUl/min,
      yielding dialysis recoveries >=45% for both assayed LMWOAs in simulated
      background soil electrolyte solutions, and >=24% in the interstitial liquid of
      complex solid samples. Full knowledge of the fate of LMWOAs in soils was obtained
      through the application of stimulus-response approaches that mimic the discrete
      exudation pulses of roots. Highly time-resolved microdialysates were used to
      discern readily available species such as free carboxylic anions and LMW metal
      organic acid complexes from adsorbed, precipitated or mineralised analyte species
      in a variety of soil samples containing variable amounts of organic matter,
      exchangeable cations and different levels of metal pollution.

PMID- 29569546
TI  - Loss of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and
      coplanar polychlorinated biphenyls during nitrogen gas blowdown process for ultra
      trace analysis.
AB  - This study examined standard solutions to assess the influence of the gas flow
      rate and organic solvent type on losses caused by gas blowdown of polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and coplanar polychlorinated
      biphenyls (Co-PCBs). Results obtained here will contribute to maintaining
      analytical method performance and system quality for PCDD/DFs and Co-PCBs
      analyses. An organic solvent (with 0.5ml each of acetone, dichloromethane, n
      hexane, and toluene), PCDD/DFs or Co-PCBs, and their 13C12-labeled compounds were
      put separately into 10ml pear-shaped flasks. The samples were blown to dryness at
      room temperature until the last trace of solvent disappeared. They were
      subsequently reconstituted in those flasks. Analyte recoveries were calculated by
      comparing blown samples to those that had not been blown. Recoveries of Co-PCBs
      were more affected than those of PCDD/DFs when the gas flow rates were set at
      203, 261, 332, and 456ml/min. Losses of Co-PCBs were least at 203-332ml/min.
      Regarding losses of PCDD/DFs and Co-PCBs, the toluene solution showed the least
      variation in recovery. An actual soil sample extract was also examined using
      optimized conditions for the gas flow rate and solvent types obtained by
      experiments in standard solutions. Thereby, the blowdown conditions gave
      quantitative recoveries of 13C12-labeled compounds in the sample extract.

PMID- 29569547
TI  - Characterization of the aroma profile of Madeira wine by sorptive extraction
      techniques.
AB  - The characterization of the aroma profile of 33 samples of Madeira wine from five
      monovarieties (Sercial, Verdelho, Boal, Malvasia and Tinta Negra Mole) having
      different type and categories is presented, using solid phase microextraction and
      stir bar sorptive extraction techniques (SPME and SBSE) followed by capillary gas
      chromatography and mass spectrometry detection (GC-MS). Headspace SPME/GC-MS
      provided effectiveness to identify the major constituents of the aroma profile of
      Madeira wine, where no remarkable differences occur among the samples studied.
      The volatile compounds are mainly constituted by ethyl octanoate (11.3-256.9MUgL
      1), ethyl decanoate (21.5-210.5MUgL-1), ethyl decenoate (0.1-112.8MUgL-1),
      diethyl succinate (0.9-65.6MUgL-1), ethyl dodecanoate (1.2-6.5MUgL-1), ethyl
      nonanoate (0.6-5.2MUgL-1), ethyl hexanoate (0.2-3.7MUgL-1) and isoamyl octanoate
      (0-2.2MUgL-1). C13 norisoprenoids such as vitispirane (0.9-7.0MUgL-1) and 1,1,6
      trimethyl 1,2-dihydro naphthalene (0.7-12.5MUgL-1), as well as phenyl ethanol (0
      8.1MUgL-1), were also found in Madeira wine samples. The powerful capabilities of
      SBSE followed thermal desorption and GC-MS analysis allowed higher ability for
      profiling traces and ultra traces of compounds in Madeira wine samples, including
      esters (80.7-89.7%), carboxylic acids (1.6-4.2%), alcohols (3.5-8.2%), aldehydes
      (0.9-3.7%), pyrans (0.2-1.7%), lactones (<3%), monoterpenes (0.1-1.4%),
      sesquiterpenes (0.1-0.8%) and C13 norisoprenoids (1.7-6.5%), which some of them
      play a remarkable impact on the aroma complexity. C13 norisoprenoids in
      particular, seem to play an important role on Madeira wine bouquet since
      presenting very low sensorial threshold limits. Excellent correlation between
      Madeira wine ageing and the abundance of cis-oak lactone was attained showing to
      be an important chemical descriptor to characterize reserves and Vintages as well
      as a contributor to wine flavour. The differentiation between reserves,
      dry/medium dry and sweet/medium sweet young wines could be well established by
      means of chemometric analysis, using particular aroma compounds such as diethyl
      succinate, cis-oak lactone and ethyl octanoate as discriminating variables.

PMID- 29569548
TI  - An assisted approach of the global optimization for the experimental conditions
      in capillary electrophoresis.
AB  - Experimental conditions have effect on the separation of capillary
      electrophoresis (CE) directly. In this work, a set of index to describe the
      separation in CE was established properly. Based on a combination of genetic
      algorithm and least square support vector machine, an assisted approach of global
      optimization for experimental conditions was proposed for the first time, and it
      was applied to the separation of four synthetic compounds by CE in nonaqueous
      system. Under the optimum conditions obtained by this approach, the result of the
      experiment was satisfactory and proved that this novel approach was effective.
      Furthermore, we investigated the most important conditions that mainly affect the
      separation effectiveness of CE by partial least squares regression analysis.
      Because of the generalization of this new approach proposed, it can be applied to
      the optimization of other experimental processes.

PMID- 29569549
TI  - Enantioseparation of dansyl amino acids by a novel permanently positively charged
      single-isomer cyclodextrin: Mono-6-N-allylammonium-6-deoxy-beta-cyclodextrin
      chloride by capillary electrophoresis.
AB  - A permanently positively charged single-isomer beta-CD, mono-6-N-allylammonium-6
      deoxy-beta-CD chloride, ALAM-beta-CD, has been synthesized and successfully used
      as chiral selector in capillary electrophoresis for enantioseparation of amino
      acids and dansyl amino acids. The effects of pH, CD's concentration and capillary
      length on enantioseparation were studied in order to investigate its potential as
      chiral selector for acidic racemates. By increasing buffer's pH and CD's
      concentration, fairly robust separations were achieved. Good separations were
      also obtained with a shorter capillary. In addition, baseline enantiomeric
      separations of a mixture of six pairs of dansyl dl-amino acids were achieved
      under different pH conditions.

PMID- 29569550
TI  - Electrochemical hydride generation atomic absorption spectrometry for
      determination of cadmium.
AB  - An electrolytic hydride generation system for determination of another hydride
      forming element, cadmium, by catholyte variation electrochemical hydride
      generation (EcHG) atomic absorption spectrometry is described. A laboratory-made
      electrolytic cell with lead-tin alloy as cathode material is designed as
      electrolytic generator of molecular hydride. The influences of several parameters
      on the analytical signal have been evaluated using a Plackett-Burman experimental
      design. The significant parameters such as cathode surface area, electrolytic
      current, carrier gas flow rate and catholyte concentration have been optimized
      using univariate method. The analytical figures of merit of procedure developed
      were determined. The calibration curve was linear up to 20ngml-1of cadmium. The
      concentration detection limit (3sigma, n=8) of 0.2ngml-1 and repeatability
      (relative standard deviation, n=7) of 3.1% were achieved at 10.0ngml-1. It was
      shown that interferences from major constituents at high concentrations were
      significant. The accuracy of method was verified using a real sample (spiked tap
      water) by standard addition calibration technique. Recovery of 104% was achieved
      for Cd in the spiked tap water sample.

PMID- 29569551
TI  - A sol-gel immobilization of nano and micron size sorbents in
      poly(dimethylsiloxane) (PDMS) microchannels for microscale solid phase extraction
      (SPE).
AB  - Sorbent particles consisting of nano and micro silica, and micron size
      octadecylsilica (ODS) were immobilized using sol-gel chemistry onto
      poly(dimethylsiloxane) (PDMS) microfluidic channels to serve as MU-chip solid
      phase extraction (SPE) devices. Extraction, preconcentration and purification of
      biological and chemical analytes were carried out using these. Micro and nano
      scale silica-immobilized MU-SPE were used for the extraction/purification of DNA
      from recombinant Escherichia coli crude lysate. The average DNA recovery was 77+/
      9% (X+/-R.S.D.) for the micron size silica particles and 70+/-5% (X+/-R.S.D.) for
      the nano silica particles. The extracted DNA could be amplified by polymerase
      chain reaction (PCR) whereas the DNA from the crude lysate solution could not be.
      This was a testimony to the purification capability of the MU-SPE device. ODS
      immobilized MU-SPE were used to study the extraction efficiency (EE) and
      enhancement factor (EF) for three groups of organic compounds, aromatics, phenols
      and carboxylic acids. They showed poor recovery and low enrichment because the
      analytes sorbed into the PDMS and were not quantitatively extracted.

PMID- 29569552
TI  - Molecularly imprinted polyethersulfone microspheres for the binding and
      recognition of bisphenol A.
AB  - BPA-imprinted polyethersulfone (PES) microspheres for the binding and recognition
      of bisphenol A (BPA) were fabricated by means of a liquid-liquid phase separation
      technique. The imprinted novel PES microspheres had a porous structure with a
      skin layer, under which was followed by a finger-like structure. The recognition
      experiments with the BPA-imprinted microspheres were carried out by applying the
      microspheres to various BPA solutions. In water, high binding amounts of BPA were
      observed in the range of 19-42MUmol/g capacity, but the recognition was low in
      the BPA water solution. With the increase of the concentration in BPA solution,
      the binding amounts and the recognition coefficient increased. However, 1,4
      butylene glycol/water media showed high recognition of the imprinted microspheres
      with a low binding capacity of BPA. In addtion, with the increase of the BPA
      amounts in the PES solution used to prepare the imprinted microspheres, the
      specific recognition sites increased, and the recognition ability increased.
      Evidence revealed that microsphere recognition was effective for BPA due to the
      binding to specific recognition sites [S](sites). The imprinted microspheres
      showed the selectivity for BPA in the wine including BPA and other organic
      compounds. Charge transfer and special cavities could be employed to explain the
      mechanism.

PMID- 29569553
TI  - Spectral filtering of light-emitting diodes for fluorescence detection.
AB  - The use of light-emitting diodes (LEDs) for fluorescence detection has recently
      gained much interest. The broad wavelength emission of LEDs requires spectral
      filtering that is not necessary when using a laser. For instance, filtering the
      LED light using a bandpass filter improves the signal-to-background ratio for
      riboflavin by a factor of 70. The bandwidth of the necessary bandpass filters
      affects both the signal and the background in these measurements. Fluorescence
      signal can be maximized with wider-bandpass high-transmittance filters.
      Background is governed by scattering of the LED emission light transmitted by two
      bandpass filters. When there is large crosstalk between the filters, the LED
      intensity is linearly related to the background. By estimating and optimizing the
      crosstalk between excitation and emission filters with a method presented here,
      the signal-to-background can be optimized. Bandpass filters should be selected
      with sharp on-off transition, strong blocking outside their transmitting region
      and the widest bandwidth with minimal crosstalk. Using optimized spectral
      filtering and capillary electrophoresis analysis, LODs of 50, 3 and 20nM are
      obtained for riboflavin, fluorescein and eosin Y, respectively. These results are
      superior to those reported in the literature for 5mW LEDs.

PMID- 29569554
TI  - Sizes of water-soluble luminescent quantum dots measured by fluorescence
      correlation spectroscopy.
AB  - In this paper, fluorescence correlation spectroscopy (FCS) was applied to measure
      the size of water-soluble quantum dots (QDs). The measurements were performed on
      a home-built FCS system based on the Stokes-Einstein equation. The obtained
      results showed that for bare CdTe QDs the sizes from FCS were larger than the
      ones from transmission electron microscopy (TEM). The brightness of QDs was also
      evaluated using FCS technique. It was found that the stability of the surface
      chemistry of QDs would be significantly improved by capping it with hard-core
      shell. Our data demonstrated that FCS is a simple, fast, and effective method for
      characterizing the fluorescent quantum dots, and is especially suitable for
      determining the fluorescent nanoparticles less than 10nm in water solution.

PMID- 29569555
TI  - Multivariate curve resolution analysis excitation-emission matrices of
      fluorescence of humic substances.
AB  - Excitation-emission matrices (EEM) of fluorescence of aqueous solutions of humic
      substances (HS), and sets of EEM acquired as function of the HS concentration,
      were analysed by multivariate curve resolution alternating least squares (MCR
      ALS). Three types of HS samples were studied: one commercial humic acid; two
      samples of fulvic acid (FA) extracted from a pinewood soil; two samples of FA
      extracted from recycled wastes. The fluorescence measurements were carried out at
      HS concentration between 5 and 100mg/L and at pH 6. The application of MCR-ALS
      algorithm on each individual EEM, as well as on column-wise augmented matrices,
      allows the identification of three major fluorophores in all HS samples analysed.
      The emission and excitation spectra of these fluorophores were recovered and are
      characteristic of each sample. Moreover, the variation of the fluorescence
      intensities of each fluorophore with HS concentration shows deviations from
      linearity at HS concentration higher than 30mg/L, depending on the fluorophore
      and/or sample. This behaviour reveals the existence of inner filter effects that
      affect the proportionally between the fluorescent signal and concentration but do
      not provoke measurable distortions on the fluorescence spectra of the detected
      fluorophores.

PMID- 29569556
TI  - Sensitive determination of captopril by time-resolved chemiluminescence using the
      stopped-flow analysis based on potassium permanganate oxidation.
AB  - The chemiluminescent behaviour of captopril when reacted with a common oxidant,
      potassium permanganate in different acidic media is described, using the stopped
      flow technique in a continuous-flow system. A 22 bit analogue-to-digital
      converter that acquires analogue signals at -10 and +10V and allows the power
      supply to the peristaltic pump to be interrupted is used in the time-resolved
      chemiluminescence manifold to ensure rapid, efficient mixing of chemiluminescent
      reagent and sample immediately before reaching the detector; this results in high
      precision and detectability, particularly with fast, short-lived emissions. The
      optimum chemical conditions for the chemiluminescence emission were investigated.
      It was found that a weak CL emission was emitted during the oxidation of this
      drug with potassium permanganate in acidic solution. The effect of common
      emission enhancers such as formic acid, formaldehyde, glutaraldehyde,
      acetaldehyde, quinine, fluorescein, rhodamine B and rhodamine 6G was studied. The
      parameters selected were 4.0molL-1 sulphuric acid, 0.25mmolL-1 permanganate and
      0.75molL-1 formaldehyde. Four quantitative parameters adjustable via software
      settings, two of them typically kinetic parameters, such as rate of the light
      development reaction and rate of the light-decay reaction, and the other
      conventional parameters, such as maximum emission intensity and total emission
      area, were used to obtain linear calibration graphs with each measurement
      parameter. The detection limits ranged from 0.011 to 0.026MUgmL-1 and R.S.D.
      values (n=10) of 1.21-3.93 at a 0.50MUgmL-1 and 2.01-3.41 at a 1.60MUgmL-1
      concentration levels were obtained. The method was satisfactorily applied to the
      determination of captopril in pharmaceutical preparations.

PMID- 29569557
TI  - The use of Nafion-coated thin mercury film electrodes for the determination of
      the dissolved copper speciation in estuarine water.
AB  - Differential pulse anodic stripping voltammetry (DPASV) using a Nafion-coated
      thin mercury film electrode (NCTMFE) was implemented to determine the dissolved
      copper speciation in saline estuarine waters containing high concentrations of
      dissolved organic matter (DOM). The study used model ligands and estuarine water
      from San Francisco Bay, California, USA to demonstrate that the NCTMFE is more
      effective at distinguishing between electrochemically inert and labile copper
      species when compared to the conventional thin mercury film electrode (TMFE).
      Copper titration results verify that the NCTMFE better deals with high
      concentrations of DOM by creating a size-exclusion barrier that prevents DOM from
      interacting with the mercury electrode when performing copper speciation
      measurements. Pseudovoltammograms were used to illustrate that copper complexes
      found in natural waters were more apt to be electrochemically inert at the NCTMFE
      relative to the TMFE when subjected to high negative overpotentials. Copper
      speciation results using the NCTMFE from samples collected in San Francisco Bay
      estimated that >99.9% of all copper was bound to strong copper-binding ligands.
      These L1-class ligands exceeded the concentration of total dissolved copper in
      all samples tested and control the equilibrium of ambient [Cu2+] in the San
      Francisco Bay estuary.

PMID- 29569558
TI  - Determination of aluminum as contaminant in dialysis concentrates by adsorptive
      cathodic stripping voltammetry.
AB  - This paper describes a stripping voltammetric method for the determination of
      aluminum as contaminant in dialysis concentrates. It is based on the adsorptive
      deposition of the complex Al-1,2-dihydroxyanthraquinone-3-sulfonic acid (DASA) at
      the hanging mercury drop electrode (HMDE) at -0.9V (versus Ag/AgCl) and its
      cathodic stripping during the potential scan. The method was optimized concerning
      the main electrochemical parameters that influence the voltammetric determination
      in highly saline solutions (sample dilution factor, deposition time and DASA
      concentration). The linear range for the measurements was from <LOD to 30MUgl-1
      with a detection limit calculated as 0.8MUgl-1 for a deposition time of 15s.
      Aluminum recoveries between 91.0 and 105.5% for spiked samples of dialysis
      concentrates proof the accuracy of the proposed voltammetric method. The method
      allows the rapid aluminum determination at MUgl-1 levels in the presence of
      Zn(II) as interfering ion, and it was applied to its determination in commercial
      dialysis concentrates used routinely by hemodialysis centers in Brazil. Aluminum
      concentrations between 9.0 and 78.7MUgl-1 were determined in five different
      samples of three kinds of dialysis concentrates.

PMID- 29569559
TI  - Electrochemical detection of the herbicide paraquat in natural water and citric
      fruit juices using microelectrodes.
AB  - A novel electroanalytical procedure for detecting the paraquat herbicide in
      natural water and citric fruit juice samples using gold microelectrodes and
      square wave voltammetry at high frequencies is proposed. The results obtained
      showed two reversible peaks for the reduction of paraquat, the first peak
      associated with the reduction of the paraquat molecule in solution, with
      subsequent adsorption of the intermediate on the electrode surface. This adsorbed
      species was shown to undergo electroreduction in a reaction associated to the
      second voltammetric peak. The variation in pH and square wave parameters
      indicated that the best conditions under which paraquat could be reduced were a
      pH of 5.0, a frequency of 1000s-1, a scan increment of 2mV and a square wave
      amplitude of 50mV. Under these conditions, the variation of the concentrations of
      paraquat from 1.00*10-6 to 1.66*10-4molL-1 presented, for peak 1, detection and
      quantification limits of 4.51 and 15.05MUgL-1 respectively in pure electrolyte
      with a recovery factor of 99.50%. The proposed analytical procedure was also
      applied to natural water samples giving recovery factors of 95.00, 89.50 and
      92.50% in three water samples collected from an urban stream. The recovery factor
      was observed to depend on the content of organic matter which was determined by
      the biochemical and chemical oxygen demand. In lemon and orange juice samples
      that were spiked with 5.70*10-5molL-1 of paraquat, the recovery factors obtained
      were 94.30 and 92.70% respectively.

PMID- 29569560
TI  - Development and complete validation of a method for the determination of dimethyl
      mercury in air and other media.
AB  - The rigorous validation of a previously developed research method for the
      determination of dimethyl mercury ((CH3)2Hg) in environmental samples is
      presented. During atmospheric analysis, (CH3)2Hg was trapped on CarbotrapTM and
      analyzed by thermal desorption, isothermal GC separation, and cold vapor atomic
      fluorescence spectrometry (CVAFS). Water samples were analyzed after direct
      purging of 100mL aliquots onto CarbotrapTM, while sediment and tissue samples
      were digested with 10mL of 25% KOH in methanol at 60 degrees C and diluted to
      40mL with methanol. An ambient air-spiking manifold, which allowed simultaneous
      replicate sampling, was constructed in a room controlled for temperature and
      humidity. (CH3)2Hg was introduced into the feed airflow (0.4m3min-1) from a well
      calibrated diffusion cell, to obtain a concentration of approximately 5.5ngm-3 as
      Hg. Samples were collected onto CarbotrapTM columns, and the total volumes
      quantified by integrating mass flow meters. Trapping efficiency was investigated
      over a range of sampler flow rates (0.05-0.25Lmin-1), volumes (2-200L),
      collection temperatures (15-42 degrees C) and relative humidity levels (10-70%).
      Method detection limits (MDLs), analytical precision and accuracy were quantified
      for all media. CarbotrapTM was found to be the best choice as a sampling media,
      whereas TenaxTM was found to be inadequate due to high breakthrough (>70%). This
      study verified that the method is sufficiently precise, accurate and robust for
      field sampling at mercury contaminated sites. No interferences were observed from
      elevated levels of potential co-contaminants, Hg0 (125ngm-3) and H2S (1.27ppmv).

PMID- 29569561
TI  - Towards Drugs and Devices Synergy. A new session track at EuroPCR: PCR clinical
      algorithms.

PMID- 29569562
TI  - A new tool to adapt the treatment of Parkinson's disease patients in nursing
      homes.
AB  - Parkinson's disease (PD) is a common condition in nursing home (NH) residents.
      The primary treatment for Parkinson's disease is levodopa therapy to relieve
      motor symptoms and maximize physical function. Non-motor symptoms are highly
      prevalent in NH residents with Parkinson's disease and dramatically decrease
      quality of life. Choices in drug treatment need to take into account the complex
      interactions between aging, comorbidity and non-motor symptoms. Optimal
      management requires expertise and cooperative effort from prescribing
      neurologists and nursing home health professionals. The objective is to evaluate
      the pertinence of the CHEF, a new tool to screen daily life clinical data helpful
      for the management of neurologist consultants. NH nurses were asked to briefly
      report falls and gait problems, hallucinations, sleep disorders and motor
      fluctuations. Analysis of the results obtained in 26 patients showed that CHEF
      was perceived as a helpful complement to existing ressources. The use of this
      tool has the potential to enhance the quality of NH care of Parkinsonian
      patients.

PMID- 29569563
TI  - The decision-making capacity of elderly hospitalized patients: validation of a
      test on their choice of return home.
AB  - Elderly hospitalized patients have uncertain or questionable capacity to make
      decisions about their care. Determining whether an elderly patient possesses
      decision-making capacity to return at home is a major concern for geriatricians
      in everyday practice. To construct and internally validate a new tool, the dream
      of home test (DROM-test), as support for decision making hospitalization
      discharge destination for the elderly in the acute or sub-acute care setting. The
      DROM-test consists of 10 questions and 4 vignettes based upon the 4 relevant
      criteria for decision-making: capacity to understand information, to appreciate
      and reason about medical risks and to communicate a choice. A prospective
      observational study was conducted during 6 months in 2 geriatric care units in
      Bretonneau Hospital (Assistance publique, Hopitaux de Paris). We compared the
      patient decision of DROM-test regarding discharge recommendations with those of
      an Expert committee and of the team in charge of the patient. 102 were included:
      mean age 83.1 + 6.7 [70; 97], 66.67% females. Principal components analysis
      revealed four dimensions: choice, understanding, reasoning and understanding. The
      area under the ROC curve was 0.64 for the choice dimension, 0.59 for the
      understanding, 0.53 for the reasoning and 0.52 for the apprehension. Only the
      choice dimension was statistically associated with the decision of the committee
      of experts (p=0.017). Even though Drom-test has limitations, it provides an
      objective way to ascertain decision-making capacity for hospitalised elderly
      patients.

PMID- 29569564
TI  - Pilot study: effectiveness of a training program about autonomy in elderly
      patients hospitalized after an acute episode.
AB  - Patients hospitalized in rehabilitation after an acute episode is at high risk of
      functional impairment and require active measures to prevent loss of autonomy.
      Resistance training has been proved beneficial to improve physical performances
      of aged subjects in the community. However, the feasibility and effects of
      training programs has never been assessed among hospitalized patients after an
      acute medical episode. In this pilot study, we aimed to evaluate a personalized
      training program of adapted physical education teacher combining muscular
      reinforcement and endurance training among patients over 65 year-old hospitalized
      in a geriatric rehabilitation care setting. The principal outcome considered was
      the evolution of the SPPB (short physical performance battery) score from
      baseline, after the 3-week period of training. Thirty-eight patients (mean age>
      80 years) participated to the program. The mean SPPB score at baseline was 6.37
      points (standard deviation: 2.17). After the intervention, the SPPB showed a
      significant improvement of 2.50 points, to reach 8.87 points (standard deviation:
      +/-1.60; p=0.001). These results confirm the feasibility of resistance-training
      programs among hospitalized elderly. The observed improvements in terms of physic
      al performances also appear promising with regard to the prevention of loss of
      autonomy during rehabilitation after acute medical episodes.

PMID- 29569565
TI  - Editorial.

PMID- 29569566
TI  - Nursing home at a crossroads.

PMID- 29569567
TI  - Posterior cortical atrophy: from vision to emotion.
AB  - In this review of the literature on posterior cortical atrophy (PCA), the history
      of the disease is first told through the studies of Frank Benson and Oliver
      Sacks. Then, we detail the possible underlying pathologies, Alzheimer's disease
      being the most common cause. Clinical, cognitive, and biological features are
      described, with a specific focus on the neuroimaging. We also describe the
      emotional aspects of PCA. These aspects are often overlooked, but deserve a
      particular attention due to their impact on the quality of life and prognostic
      implications for the patients. A multilevel care strategy for PCA patients is
      suggested.

PMID- 29569568
TI  - Successful aging: analysis of the components of a gerontological paradigm.
AB  - Since the mid-20th century, scientist has been searching the components of
      successful or active aging. At the beginning of the 21st century, demographic
      aging is now a global issue and successful aging has emerged as a gerontological
      paradigm through nation and international policies. Conducting a comprehensive
      review of scientific literature on this paradigm offers the opportunity to
      identify the key components of successful aging. Based on the results of this
      approach, we show that the components are not limited to the functional and
      cognitive health of individuals. Multidimensionality of successful aging
      highlights the complexity of factors influencing the experiences of aging, and
      the variety of dimensions involved: functional, psychological, social, spiritual
      or environmental. Representations and aspirations of what would be successful
      aging differ from one society to another, from culture to another. The article
      proposes a framework for an exploratory analysis of the vulnerabilities of
      elderly not to assess the success of aging, but to capture the components of the
      well-being of people in old age.

PMID- 29569569
TI  - Vitamin D in adults: update on testing and supplementation.
AB  - Hypovitaminosis D, a frequent condition in adults, is accompanied by adverse
      skeletal and non-skeletal events. The objective of the present article was to
      propose an update on the indications and use of vitamin D testing and
      supplementation in adults. Among healthy middle-aged adults, the serum 25
      hydroxyvitamin D (25(OH)D) target concentration is 50 nmol/L. Natural intakes
      (sun exposure and diet) are sufficient, and there is no indication for systematic
      blood test or supplementation. In middle-aged adults who are either sick or
      dependent or frail, natural intakes are generally insufficient but should be
      encouraged. In this population, the loading phase of the supplementation targets
      a 25(OH)D concentration of 75 nmol/L, and the pattern of supplementation (200,000
      to 400,000 IU orally over 2 months) depends on the measure of circulating 25(OH)D
      (which is not reimbursed outside the scope defined by the French national
      authority for health). In adults over 65 years of age, the loading phase of the
      supplementation should be systematic and targets a concentration of 75 nmol/L
      (pattern of 300,000 IU orally over 3 months). Regardless of age, the loading
      phase should be followed by a long-term maintenance phase of supplementation to
      maintain the 25(OH)D concentration above the target. A measure of serum 25(OH)D
      is useful after 9 months of supplementation to adjust the frequency or dosage of
      supplements if necessary.

PMID- 29569570
TI  - Behavioral and psychological symptoms in Lewy body disease: a review.
AB  - Dementia with Lewy bodies (DLB) is a common neurodegenerative disease, second in
      terms of prevalence after Alzheimer's disease (AD). DLB may be suspected
      according to three core features which are cognitive and motor fluctuations,
      early visual hallucinations and parkinsonism; and more recently, according to the
      new criteria, REM sleep behavior disorder (RBD). Behavorial and psychological
      symptoms associated with DLB are more frequent, more severe and appear earlier
      than those found in other neurodegenerative diseases. They may be at the
      forefront and are a major diagnostic and therapeutic challenge. An improved
      knowledge of the pathophysiology and phenomenology associated to these symptoms
      can facilitate their identification as well as eliminating differential
      diagnoses. Managing these symptoms may require drugs when hallucinations are
      overwhelming and induce behavorial disorders. However, psychotropic medications
      are not well tolerated in this specific population and some antipsychotic drugs
      cannot be prescribed due to their side effects. Although further studies are
      needed on this subject, non-interventional treatments such as therapeutic
      strategies based on the patients and their caregivers appear to be essential.
      This paper offers a review which aims to help clinicians to identify behavioral
      and psychological symptoms in DLB and treat them in their daily practice.

PMID- 29569571
TI  - A foldable electrode array for 3D recording of deep-seated abnormal brain
      cavities.
AB  - OBJECTIVE: This study describes the design and microfabrication of a foldable
      thin-film neural implant and investigates its suitability for electrical
      recording of deep-lying brain cavity walls. APPROACH: A new type of foldable
      neural electrode array is presented, which can be inserted through a cannula. The
      microfabricated electrode is specifically designed for electrical recording of
      the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept
      is demonstrated by measurements in rat brain cavities. On implantation, the
      electrode array unfolds in the brain cavity, contacting the cavity walls and
      allowing recording at multiple anatomical locations. A three-layer
      microfabrication process based on UV-lithography and Reactive Ion Etching is
      described. Electrochemical characterization of the electrode is performed in
      addition to an in vivo experiment in which the implantation procedure and the
      unfolding of the electrode are tested and visualized. MAIN RESULTS:
      Electrochemical characterization validated the suitability of the electrode for
      in vivo use. CT imaging confirmed the unfolding of the electrode in the brain
      cavity and analysis of recorded local field potentials showed the ability to
      record neural signals of biological origin. SIGNIFICANCE: The conducted research
      confirms that it is possible to record neural activity from the inside wall of
      brain cavities at various anatomical locations after a single implantation
      procedure. This opens up possibilities towards research of abnormal brain
      cavities and the clinical conditions associated with them, such as central post
      stroke pain.

PMID- 29569572
TI  - Squeezed vacuum states of light for gravitational wave detectors.
AB  - A century after Einstein's formulation of General Relativity, the detectors of
      the Laser Interferometer Gravitational-wave Observatory (LIGO) made the first
      direct detection of gravitational waves. This historic achievement was the
      culmination of a world-wide effort and decades of instrument research. While
      sufficient for this monumental discovery, the current generation of gravitational
      wave detectors represent the least sensitive devices necessary for the task;
      improved detectors will be required to fully exploit this new window on the
      Universe. In this paper, we review the application of squeezed vacuum states of
      light to gravitational-wave detectors as a way to reduce quantum noise, which
      currently limits their performance in much of the detection band.

PMID- 29569573
TI  - Chronic softening spinal cord stimulation arrays.
AB  - OBJECTIVE: We sought to develop a cervical spinal cord stimulator for the rat
      that is durable, stable, and does not perturb the underlying spinal cord.
      APPROACH: We created a softening spinal cord stimulation (SCS) array made from
      shape memory polymer (SMP)-based flexible electronics. We developed a new
      photolithographic process to pattern high surface area titanium nitride (TiN)
      electrodes onto gold (Au) interconnects. The thiol-ene acrylate polymers are
      stiff at room temperature and soften following implantation into the body.
      Durability was measured by the duration the devices produced effective
      stimulation and by accelerated aging in vitro. Stability was measured by the
      threshold to provoke an electromyogram (EMG) muscle response and by measuring
      impedance using electrochemical impedance spectroscopy (EIS). In addition, spinal
      cord modulation of motor cortex potentials was measured. The spinal column and
      implanted arrays were imaged with MRI ex vivo, and histology for astrogliosis and
      immune reaction was performed. MAIN RESULTS: For durability, the design of the
      arrays was modified over three generations to create an array that demonstrated
      activity up to 29 weeks. SCS arrays showed no significant degradation over a
      simulated 29 week period of accelerated aging. For stability, the threshold for
      provoking an EMG rose in the first few weeks and then remained stable out to 16
      weeks; the impedance showed a similar rise early with stability thereafter.
      Spinal cord stimulation strongly enhanced motor cortex potentials throughout.
      Upon explantation, device performance returned to pre-implant levels, indicating
      that biotic rather than abiotic processes were the cause of changing metrics. MRI
      and histology showed that softening SCS produced less tissue deformation than
      Parylene-C arrays. There was no significant astrogliosis or immune reaction to
      either type of array. SIGNIFICANCE: Softening SCS arrays meet the needs for
      research-grade devices in rats and could be developed into human devices in the
      future.

PMID- 29569574
TI  - Improved muscle activation using proximal nerve stimulation with subthreshold
      current pulses at kilohertz-frequency.
AB  - OBJECTIVE: Transcutaneous electrical nerve stimulation can help individuals with
      neurological disorders to regain their motor function by activating muscles
      externally. However, conventional stimulation technique often induces near
      simultaneous recruitment of muscle fibers, leading to twitch forces time-locked
      to the stimulation. APPROACH: To induce less synchronized activation of finger
      flexor muscles, we delivered clustered narrower pulses to the proximal segment of
      the median and ulnar nerves at a carrier frequency of either 10 kHz (with an 80
      us pulse width) or 7.14 kHz (with a 120 us pulse width) (high-frequency mode,
      HF), and different clustered pulses were delivered at a frequency of 30 or 40 Hz.
      Conventional stimulation with pulse frequency of 30 or 40 Hz (low-frequency mode,
      LF) was used for comparison. With matched elicited muscle forces between the HF
      and LF modes, the force variation, the high-density electromyogram (EMG) signals
      recorded at the finger flexor muscles and stimulation-induced-pain levels were
      compared. MAIN RESULTS: The compound action potentials in the 10 kHz HF mode
      revealed a significant difference (i.e. a lower amplitude and area, and a wider
      duration) compared with the LF mode, indicating cancellations of asynchronized
      action potentials. A smaller fluctuation in the elicited forces in the 10 kHz
      mode further demonstrated the less synchronized activation of different motor
      units. These effects tended to be weaker in the 7.14 kHz HF condition. However,
      the levels of pain sensation was not reduced in the HF mode potentially due to
      the high charge density used in the HF mode. Our findings indicated that
      different nerve fibers were recruited asynchronously through summations of
      different numbers of subthreshold depolarizations in the HF mode. SIGNIFICANCE:
      Compared with the LF mode, the HF mode stimulation was capable of activating the
      nerve fibers in a less synchronized way, which is more similar to the
      physiological activation pattern.

PMID- 29569575
TI  - WIMP dark matter candidates and searches-current status and future prospects.
AB  - We review several current aspects of dark matter theory and experiment. We
      overview the present experimental status, which includes current bounds and
      recent claims and hints of a possible signal in a wide range of experiments:
      direct detection in underground laboratories, gamma-ray, cosmic ray, x-ray,
      neutrino telescopes, and the LHC. We briefly review several possible particle
      candidates for a weakly interactive massive particle (WIMP) and dark matter that
      have recently been considered in the literature. We pay particular attention to
      the lightest neutralino of supersymmetry as it remains the best motivated
      candidate for dark matter and also shows excellent detection prospects. Finally
      we briefly review some alternative scenarios that can considerably alter
      properties and prospects for the detection of dark matter obtained within the
      standard thermal WIMP paradigm.

PMID- 29569576
TI  - Urinary tract infection due to Fusarium oxysporum in an immunocompetent patient
      with chronic kidney disease.
AB  - Infections due to Fusarium species are collectively referred to as fusariosis.
      Fusarium oxysporum has been reported to cause keratitis, onychomycosis, skin
      infections, catheter associated fungemia and has not been described as a cause of
      urinary tract infection. Here, we present the first case of fusariosis with
      urinary tract involvement in a 67 year old male, with chronic kidney disease and
      type 2 diabetes mellitus. This case illustrates the ever increasing spectrum of
      rare but offending pathogenic fungi. Early diagnosis of infection with a specific
      pathogen may lead to changes in antifungal therapy and may be critical for an
      improved outcome.

PMID- 29569577
TI  - Effects of volatile anesthetic preconditioning on expression of NFkB-regulated
      genes in aged rat myocardium.
AB  - Volatile anesthetic preconditioning has been shown to be a potent way to provide
      myocardium protection against ischemia/reperfusion (I/R) injury; however, this
      cardioprotection is lost in senescent animal models and elderly patients. NFkB
      regulated genes have been linked to myocardial I/R injury and anesthetic
      preconditioning. Here, we investigated NFkB activation related to anesthetic
      preconditioning in aging rat myocardium. Isolated, Langendorff perfused rat
      hearts from Fischer 344 male rats, 24 months old, were randomly assigned to one
      of the three groups. The hearts of the control group were perfused with
      physiologic solution without any intervention. The hearts in the I/R group were
      subjected to 25 minutes ischemia and followed by 60 minutes reperfusion. The
      hearts in the treatment group were subjected to 10 minutes 2.5% sevoflurane,
      followed by 20 minutes washout and by 25 minutes ischemia and 60 minutes of
      reperfusion, respectively. Left ventricular developed pressure (LVDP) and left
      ventricular end-diastolic pressure (LVEDP) were measured. Western blot analysis
      was used to measure inhibitor of kB (IkB) and anti-apoptotic genes: A1, ILP, c
      IAP-2, Bcl-2, caspase 8 and caspase 9. Ischemia and reperfusion significantly
      decreased LVDP and increased LVEDP in aged rat hearts. Anesthetic preconditioning
      with sevoflurane did not change the effects I/R on LVDP and LVEDP, despite the
      fact that after treatment with anesthetic preconditioning, the levels of IkappaB,
      A1, ILP, caspase 8 and caspase 9 were significantly different compared to those
      of the control hearts. In conclusion, anesthetic preconditioning with sevoflurane
      does not improve myocardial systolic and diastolic functions. Our results suggest
      that the activation of NFkB regulated genes is different in the senescent
      myocardium and could account for loss of cardioprotection with aging.

PMID- 29569578
TI  - Author Correction: TRPC5 channels participate in pressure-sensing in aortic
      baroreceptors.
AB  - This corrects the article DOI: 10.1038/ncomms11947.

PMID- 29569579
TI  - Erratum: CORRIGENDUM: Fault-tolerant quantum computation with a soft-decision
      decoder for error correction and detection by teleportation.
AB  - This corrects the article DOI: 10.1038/srep05771.

PMID- 29569582
TI  - Smart brush tool now software integrated.

PMID- 29569583
TI  - Does relative analgesia with nitrous oxide reduce the number of general
      anaesthetic sessions and dental loss?

PMID- 29569584
TI  - PERSONAL ACCOUNT: The benefits of joining the British College of Aesthetic
      Medicine.

PMID- 29569581
TI  - Genetic basis for childhood interstitial lung disease among Japanese infants and
      children.
AB  - BackgroundGenetic variants responsible for childhood interstitial lung disease
      (chILD) have not been studied extensively in Japanese patients.MethodsThe study
      population consisted of 62 Japanese chILD patients. Twenty-one and four patients
      had pulmonary hypertension resistant to treatment (PH) and hypothyroidism,
      respectively. Analyses of genetic variants were performed in all 62 patients for
      SFTPC and ABCA3, in all 21 PH patients for FOXF1, and in a limited number of
      patients for NKX2.1.ResultsCausative genetic variants for chILD were identified
      in 11 (18%) patients: SFTPC variants in six, NKX2.1 variants in three, and FOXF1
      variants in two patients. No patients had ABCA3 variants. All three and two
      patients with NKX2.1 variants had hypothyroidism and developmental delay,
      respectively. We found six novel variants in this study.ConclusionMutations in
      SFTPC, NKX2.1, and FOXF1 were identified among Japanese infants and children with
      chILD, whereas ABCA3 mutations were rare.

PMID- 29569586
TI  - A fully streamlined implant system.

PMID- 29569585
TI  - Special care dentistry: Dementia-friendly.

PMID- 29569588
TI  - New academy focuses on bone and tissue regeneration.

PMID- 29569587
TI  - Dental volunteering: An invaluable experience.

PMID- 29569589
TI  - Save time without the compromise.

PMID- 29569590
TI  - Developments in dental sleep appliances.

PMID- 29569591
TI  - Notice of death.

PMID- 29569592
TI  - Orthodontic procurement exercise condemned.

PMID- 29569593
TI  - Motivate patients with new whitening toothpastes.

PMID- 29569594
TI  - Robin M. Basker.

PMID- 29569595
TI  - Updated dental radiography guideline.

PMID- 29569596
TI  - Highlighting preventive dentistry from an early age.

PMID- 29569597
TI  - Gordon Fordyce.

PMID- 29569599
TI  - Workforce planning: Meeting future needs.

PMID- 29569598
TI  - Correction.
AB  - This corrects the article DOI: 10.1038/sj.bdj.2017.999.

PMID- 29569600
TI  - Modern biotech and ancient minerals in a toothpaste.

PMID- 29569601
TI  - BDA UPDATE.

PMID- 29569602
TI  - A game-changer in implant dentistry.

PMID- 29569603
TI  - NHS dentistry: Culture of fear.

PMID- 29569604
TI  - Wheelchair users: a guide for the GDP.
AB  - The number of wheelchair users in the UK is increasing, and it may be more
      convenient and appropriate for many of these individuals to receive their dental
      care in a general dental practice rather than in a community or tertiary
      facility. This article is intended to provide the average general dental
      practitioner (GDP) with the basic tools and increased confidence to effectively
      triage this cohort of the population, and accept them for treatment or refer
      appropriately.

PMID- 29569605
TI  - Information Governance Toolkit publishing deadline reminder.

PMID- 29569606
TI  - Spot what's not visible to the naked eye.

PMID- 29569608
TI  - Direct or indirect post crowns to restore compromised teeth: a review of the
      literature.
AB  - Post crowns are restorations which utilise the root canal space to improve the
      retention and resistance form of teeth which lack coronal tooth structure. In
      recent years there have been significant developments in the materials, systems
      and evidence-base surrounding the provision of post crowns. This review aims to
      refresh the general dental practitioner's (GDPs) knowledge of the different
      factors that must be considered when placing a post crown, and how these factors
      can help guide the dentist in their decision to provide either a direct or
      indirect post and core.

PMID- 29569609
TI  - Smell the spring air.

PMID- 29569610
TI  - New advice on feeding and weaning babies to reduce tooth decay risk.

PMID- 29569607
TI  - The oral microbiota - a mechanistic role for systemic diseases.
AB  - Human oral microbiota is the ecological community of commensal, symbiotic, and
      pathogenic microorganisms found in the oral cavity. Oral microbiota generally
      exists in the form of a biofilm and plays a crucial role in maintaining oral
      homeostasis, protecting the oral cavity and preventing disease development. Human
      oral microbiota has recently become a new focus research for promoting the
      progress of disease diagnosis, assisting disease treatment, and developing
      personalised medicines. In this review, the scientific evidence supporting the
      association that endogenous and exogenous factors (diet, smoking, drinking,
      socioeconomic status, antibiotics use and pregnancy) modulate oral microbiota. It
      provides insights into the mechanistic role in which oral microbiota may
      influence systemic diseases, and summarises the challenges of clinical diagnosis
      and treatment based on the microbial community information. It provides
      information for noninvasive diagnosis and helps develop a new paradigm of
      personalised medicine. All these benefit human health in the post-metagenomics
      era.

PMID- 29569611
TI  - Common sense please.

PMID- 29569613
TI  - A super-duper autoclave.

PMID- 29569612
TI  - An update on the evidence for pathogenic mechanisms that may link periodontitis
      and diabetes.
AB  - Elevated pro-inflammatory factors in the gingiva of patients with poorly
      controlled diabetes suggests a biological pathway that may aggravate
      periodontitis.

PMID- 29569614
TI  - State-of-the-art children's dental practice opens.

PMID- 29569615
TI  - Business experts to hold workshop.

PMID- 29569616
TI  - FELLOWSHIP PROGRAMME: National Dental Clinical Fellow Scheme now open for
      applications.

PMID- 29569617
TI  - Peri-implant conditions and levels of advanced glycation end products among
      patients with different glycemic control.
AB  - AGEs may be considered as potential marker of inflammation in diabetic
      individuals with peri-implantitis.

PMID- 29569618
TI  - Digital health technology and diabetes management.
AB  - Digital diabetes care demonstrated only modest HbA1c reduction in multiple
      studies and borderline cost-effectiveness, although patient satisfaction appeared
      to be increased.

PMID- 29569619
TI  - A systematic review and meta-analysis of epidemiologic observational evidence on
      the effect of periodontitis on diabetes. An update of the EFP-AAP review.
AB  - Periodontitis affects glycaemic control in health and diabetes.

PMID- 29569620
TI  - Diseases associated with mandibular third molar teeth.

PMID- 29569623
TI  - Alzheimer disease: Epigenetics links ageing with Alzheimer disease.

PMID- 29569621
TI  - Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine and
      metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is
      defined by a combination of signs and symptoms of androgen excess and ovarian
      dysfunction in the absence of other specific diagnoses. The aetiology of this
      syndrome remains largely unknown, but mounting evidence suggests that PCOS might
      be a complex multigenic disorder with strong epigenetic and environmental
      influences, including diet and lifestyle factors. PCOS is frequently associated
      with abdominal adiposity, insulin resistance, obesity, metabolic disorders and
      cardiovascular risk factors. The diagnosis and treatment of PCOS are not
      complicated, requiring only the judicious application of a few well-standardized
      diagnostic methods and appropriate therapeutic approaches addressing
      hyperandrogenism, the consequences of ovarian dysfunction and the associated
      metabolic disorders. This article aims to provide a balanced review of the latest
      advances and current limitations in our knowledge about PCOS while also providing
      a few clear and simple principles, based on current evidence-based clinical
      guidelines, for the proper diagnosis and long-term clinical management of women
      with PCOS.

PMID- 29569622
TI  - Global epidemiology of hyperthyroidism and hypothyroidism.
AB  - Thyroid hormones are essential for growth, neuronal development, reproduction and
      regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common
      conditions with potentially devastating health consequences that affect all
      populations worldwide. Iodine nutrition is a key determinant of thyroid disease
      risk; however, other factors, such as ageing, smoking status, genetic
      susceptibility, ethnicity, endocrine disruptors and the advent of novel
      therapeutics, including immune checkpoint inhibitors, also influence thyroid
      disease epidemiology. In the developed world, the prevalence of undiagnosed
      thyroid disease is likely falling owing to widespread thyroid function testing
      and relatively low thresholds for treatment initiation. However, continued
      vigilance against iodine deficiency remains essential in developed countries,
      particularly in Europe. In this report, we review the global incidence and
      prevalence of hyperthyroidism and hypothyroidism, highlighting geographical
      differences and the effect of environmental factors, such as iodine
      supplementation, on these data. We also highlight the pressing need for detailed
      epidemiological surveys of thyroid dysfunction and iodine status in developing
      countries.

PMID- 29569625
TI  - Epilepsy: A role for expanded DNA repeats in familial epilepsy.

PMID- 29569626
TI  - Epilepsy: Timely treatment of refractory convulsive status epilepticus.

PMID- 29569627
TI  - [Selected risk factors for occupational exposures to blood-borne pathogens in
      cosmetics salons].
AB  - BACKGROUND: Services offered in the esthetic/beauty industry poses the risk of
      blood-borne infections (BBIs) due to carrying out invasive procedures. The study
      objective: was to assess the number of sharps injuries, occupational risk
      factors, and preventive methods used among cosmetologists. MATERIAL AND METHODS:
      The anonymous survey was conducted (February-April 2017) in randomly selected
      beauty/esthetic medicine clinics in Szczecin, Poland; 96 cosmetologists were
      invited. RESULTS: Eighty cosmetologists (83.3%), responded. The mean age of the
      group was 25 years (range: 20-60 years). The majority of the respondents (95%)
      used sharps while at work, 41.3% had suffered at least one sharps injury during
      their occupational career. Clippers were the most common injury-causing
      instrument (39.4%), and manicure/pedicure was the most common injury-causing
      procedure (51.5%); 84.8% of injuries were not reported. The number of injuries
      was associated with age (34.9% in the group of 20-29 years old respondents vs.
      64.7% in respondents >= 30 years old, p = 0.05), work experience (32.6% in the
      respondents working for 1-3 years vs. 68.8%, in those working >= 7 years, p =
      0.03), and working hours/week (28.9% in those working <= 40 h vs. 57.1% of those
      working > 40 h, p = 0.02). Needle recapping was reported by 47.5% of respondents,
      13.8% did not dispose used needles into a container, 17.5% did not routinely use
      gloves. CONCLUSIONS: Cosmetologists are at risk of sharps injuries. Inconsistent
      use of preventive methods and failure to report incidents may result in
      contracting BBIs. There is a need to implement education and intervention
      measures to prevent occupational injuries, particularly with regard to
      cosmetologists aged over 30 years, with a longer professional experience, working
      over 40 h/week. Med Pr 2018;69(3):281-290.

PMID- 29569624
TI  - Physiological changes in neurodegeneration - mechanistic insights and clinical
      utility.
AB  - The effects of neurodegenerative syndromes extend beyond cognitive function to
      involve key physiological processes, including eating and metabolism, autonomic
      nervous system function, sleep, and motor function. Changes in these
      physiological processes are present in several conditions, including
      frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the
      parkinsonian plus conditions. Key neural structures that mediate physiological
      changes across these conditions include neuroendocrine and hypothalamic pathways,
      reward pathways, motor systems and the autonomic nervous system. In this Review,
      we highlight the key changes in physiological processing in neurodegenerative
      syndromes and the similarities in these changes between different progressive
      neurodegenerative brain conditions. The changes and similarities between
      disorders might provide novel insights into the human neural correlates of
      physiological functioning. Given the evidence that physiological changes can
      arise early in the neurodegenerative process, these changes could provide
      biomarkers to aid in the early diagnosis of neurodegenerative diseases and in
      treatment trials.

PMID- 29569628
TI  - Correction to: Current therapies in alleviating liver disorders and cancers with
      a special focus on the potential of vitamin D.
AB  - [This corrects the article DOI: 10.1186/s12986-018-0251-5.].

PMID- 29569629
TI  - Corrigendum: Metastatic Extramammary Paget's Disease: Pathogenesis and Novel
      Therapeutic Approach.
AB  - [This corrects the article on p. 38 in vol. 8, PMID: 29503810.].

PMID- 29569630
TI  - Erratum: Excessive anterior cervical muscle tone affects hyoid bone kinetics
      during swallowing in healthy individuals [Corrigendum].
AB  - [This corrects the article on p. 1903 in vol. 12, PMID: 29184396.].

PMID- 29569631
TI  - Therapeutic deep brain stimulation worsening dysprosody in Parkinson's disease -
      an unexplored entity.

PMID- 29569632
TI  - Corrigendum: In Vivo Isotopic Labeling of Symbiotic Bacteria Involved in
      Cellulose Degradation and Nitrogen Recycling within the Gut of the Forest
      Cockchafer (Melolontha hippocastani).
AB  - [This corrects the article on p. 1970 in vol. 8, PMID: 29075241.].

PMID- 29569633
TI  - A Critical Analysis of the Scientific and Commercial Rationales for the De Novo
      Synthesis of Horsepox Virus.
AB  - This article evaluates the scientific and commercial rationales for the synthesis
      of horsepox virus. I find that the claimed benefits of using horsepox virus as a
      smallpox vaccine rest on a weak scientific foundation and an even weaker business
      case that this project will lead to a licensed medical countermeasure. The
      combination of questionable benefits and known risks of this dual use research
      raises serious questions about the wisdom of undertaking research that could be
      used to recreate variola virus. This analysis also raises important questions
      about the propriety of a private company sponsoring such dual use research
      without appropriate oversight and highlights an important gap in United States
      dual use research regulations.

PMID- 29569634
TI  - Response: Commentary: Belatacept Does Not Inhibit Follicular T Cell-Dependent B
      Cell Differentiation in Kidney Transplantation.

PMID- 29569635
TI  - Corrigendum: Pseudomonas aeruginosa Takes a Multi-Target Approach to Achieve
      Junction Breach.
AB  - [This corrects the article on p. 532 in vol. 7, PMID: 29379773.].

PMID- 29569636
TI  - Correction to: Methylation of ZNF331 is an independent prognostic marker of
      colorectal cancer and promotes colorectal cancer growth.
AB  - [This corrects the article DOI: 10.1186/s13148-017-0417-4.].

PMID- 29569637
TI  - Towards distribution-based control of social networks.
AB  - Background: Complex networks are found in many domains and the control of these
      networks is a research topic that continues to draw increasing attention. This
      paper proposes a method of network control that attempts to maintain a specified
      target distribution of the network state. In contrast to many existing network
      control research works, which focus exclusively on structural analysis of the
      network, this paper also accounts for user actions/behaviours within the network
      control problem. Methods: This paper proposes and makes use of a novel
      distribution-based control method. The control approach is applied within a
      simulation of the real-valued voter model, which could have applications in
      problems such as the avoidance of consensus or extremism. The network control
      problem under consideration is investigated using various theoretical network
      types, including scale free, random, and small world. Results: It is argued that
      a distribution-based control approach may be more appropriate for several types
      of social control problems, in which the exact state of the system is of less
      interest than the overall system behaviour. The preliminary results presented in
      this paper demonstrate that a standard reinforcement learning approach is capable
      of learning a control signal selection policy to prevent the network state
      distribution from straying far from a specified target distribution. Conclusions:
      In summary, the results presented in this paper demonstrate the feasibility of a
      distribution-based control solution within the simulated problem. Additionally,
      several interesting questions arise from these results and are discussed as
      potential future work.

PMID- 29569638
TI  - Erratum: Correction of Acknowledgements.
AB  - [This corrects the article on p. 95 in vol. 61, PMID: 29372155.].

PMID- 29569639
TI  - A Holistic Assessment of the Risks and Benefits of the Synthesis of Horsepox
      Virus.
AB  - The re-creation of horsepox virus, an extinct orthopoxvirus with similarity to
      smallpox virus, has caused concerns in the biosecurity and biodefense communities
      that the technical capabilities achieved could advance the re-creation of
      smallpox virus by nefarious actors. The work is now published. While the authors
      went through due biosecurity diligence at their research institution and with the
      proper Canadian federal authorities, now that the experiments have been
      published, there is an opportunity to discuss the dual use risks and benefits of
      the research itself, as well as those associated with publication of such
      research-all of which challenge current policies. Here, an analytical framework
      is used to assess the risks and benefits of such dual use research, and relevant
      components of biosecurity policy and the biodefense enterprise (including the
      acquisition of medical countermeasures) in the United States are discussed. The
      authors emphasize the need to use such risk/benefit assessments at the onset of
      research and throughout its development, followed by an assessment for its
      responsible communication.

PMID- 29569640
TI  - Comment on: Delayed intestinal perforation and vertebral osteomyelitis after high
      intensity focused ultrasound treatment for uterine leiomyoma.

PMID- 29569641
TI  - Reader's Forum.

PMID- 29569642
TI  - Erratum: Correction of Affiliation.
AB  - [This corrects the article on p. 612 in vol. 60, PMID: 29184873.].

PMID- 29569643
TI  - Pediatric sarcomas.
AB  - [This retracts the article DOI: 10.3892/ol.2017.7467.].

PMID- 29569644
TI  - Erratum: Ex vivo distribution of gold nanoparticles in choroidal melanoma
      [Corrigendum].
AB  - [This corrects the article on p. 8527 in vol. 12, PMID: 29270009.].

PMID- 29569645
TI  - Commentary: Developmental Constraints on Learning Artificial Grammars with Fixed,
      Flexible, and Free Word Order.

PMID- 29569646
TI  - Erratum: Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in
      Adolescent Offspring with Hypoxic Ischemic Injury.
AB  - [This corrects the article on p. 306 in vol. 10, PMID: 29018327.].

PMID- 29569647
TI  - Corrigendum: The Cell Cycle Checkpoint Regulator ATR Is Required for Internal
      Aluminum Toxicity-Mediated Root Growth Inhibition in Arabidopsis.
AB  - [This corrects the article on p. 118 in vol. 9, PMID: 29491872.].

PMID- 29569648
TI  - Erratum: This Article Corrects: "GLASS Clinical Decision Rule Applied to
      Thoracolumbar Spinal Fractures in Patients Involved in Motor Vehicle Crashes".
AB  - [This corrects the article on p. 1108 in vol. 18, PMID: 29085544.].

PMID- 29569649
TI  - Commentary: Effect of Levothyroxine on Miscarriage among Women with Normal
      Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and
      Embryo Transfer: A Randomized Clinical Trial.

PMID- 29569650
TI  - Anonymizing and Sharing Medical Text Records.
AB  - Health information technology has increased accessibility of health and medical
      data and benefited medical research and healthcare management. However, there are
      rising concerns about patient privacy in sharing medical and healthcare data. A
      large amount of these data are in free text form. Existing techniques for privacy
      preserving data sharing deal largely with structured data. Current privacy
      approaches for medical text data focus on detection and removal of patient
      identifiers from the data, which may be inadequate for protecting privacy or
      preserving data quality. We propose a new systematic approach to extract,
      cluster, and anonymize medical text records. Our approach integrates methods
      developed in both data privacy and health informatics fields. The key novel
      elements of our approach include a recursive partitioning method to cluster
      medical text records based on the similarity of the health and medical
      information and a value-enumeration method to anonymize potentially identifying
      information in the text data. An experimental study is conducted using real-world
      medical documents. The results of the experiments demonstrate the effectiveness
      of the proposed approach.

PMID- 29569651
TI  - Resistant to Targeted Therapy - Aim for Metabolic Liabilities.
AB  - The advent of targeted therapies generated much optimism when discovered.
      Targeted therapies, are however associated with rapid acquisition of resistance.
      In a recent study by Dong et al. (Theranostics 2018; 8(7):1808-1823.
      doi:10.7150/thno.23177) it was shown that lung tumors resistant to the EGFR
      inhibitor (Erlotinib), reprogram their metabolism and acquire a pro-survival
      dependency on Phosphoglycerate Dehydrogenase (PHGDH) that can be targeted to
      eliminate resistant tumors.

PMID- 29569652
TI  - Molecular Analysis of Influenza A(H3N2) and A(H1N1)pdm09 Viruses circulating in
      the Democratic Republic of Congo, 2014.
AB  - Background: Very little is known about influenza viruses circulating in the
      Democratic Republic of Congo (DRC). We aim to characterize genetically and
      antigenically Influenza A(H3N2) and A(H1N1)pdm09 viruses circulating in the
      country. Methods: From August to December 2014, specimens were collected from
      patients with influenza like-illness (ILI) or severe acute respiratory infection
      (SARI) in various surveillance sites. Specimens were tested using real time
      reverse transcription polymerase chain reaction (RT-PCR) method for the detection
      of influenza viruses. Positive influenza samples with a cycle threshold (Ct) <30
      were genetically and antigenically characterized. Results: 32 samples tested were
      found positive to influenza A with Ct <30. At CDC Atlanta, 28 out of 32 samples
      (88%) were tested positive for influenza A virus, including 26 seasonal influenza
      A viruses subtype H3N2 and 2 pandemic influenza A viruses subtype H1N1pdm 2009.
      The majority of influenza A(H3N2) viruses were antigenically related to the
      A/Switzerland/9715293/2013 vaccine virus, while two influenza A(H1N1)pdm09
      isolates were antigenically characterized as A/California/07/2009-like. All
      A(H3N2) and A(H1N1)pdm09 virus isolates characterized were sensitive to
      oseltamivir and zanamivir. Conclusion: Two genetically distinct influenza
      subtypes were co-circulating in the DRCongo. Effective measures against influenza
      have been suggested.

PMID- 29569653
TI  - Cultural Theory of Risk as a Heuristic for Understanding Perceptions of Oil and
      Gas Development in Eastern Montana, USA.
AB  - This paper applies Douglas' cultural theory of risk to understand perceptions of
      risk associated with oil and gas development in eastern Montana. Based on the
      analysis of interviews with 36 rural residents, findings show the dominant
      perception of risk is most closely aligned with an Individualist worldview.
      Despite direct experience with oil or wastewater spills, most interviewees
      described spills as "no big deal", viewed nature as resilient, and felt that the
      economic benefits outweigh negative impacts. Cultural theory was a useful
      heuristic for understanding this dominant worldview, as well as identifying
      points of deviation. For example, interviewees discussed the benefits of
      landowner associations - a more Egalitarian approach to dealing with oil
      companies. Some landowners relied on external authorities (e.g., sheriff) when
      dealing with oil companies, revealing a Hierarchical approach to issues they
      face. Interviewees expressed frustration with the lack of enforcement of existing
      regulations, which can be interpreted as either support for - or indictment of -
      Hierarchical solutions. While the Individualist worldview is dominant, our
      qualitative analysis reveals the complex tensions at work among rural residents.
      The results suggest areas where policymakers, advocacy groups, and residents may
      find common ground to address potential environmental and health risks.

PMID- 29569654
TI  - Correction: A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as
      GAP toward RAB40C.
AB  - [This corrects the article DOI: 10.18632/oncotarget.19960.].

PMID- 29569655
TI  - Correction: B7-H4 as an independent prognostic indicator of cancer patients: a
      meta-analysis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.18566.].

PMID- 29569656
TI  - Correction: Aptamer: A potential oligonucleotide nanomedicine in the diagnosis
      and treatment of hepatocellular carcinoma.
AB  - [This corrects the article DOI: 10.18632/oncotarget.23359.].

PMID- 29569657
TI  - Regorafenib for the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a worldwide problem, with a high prevalence in
      nonindustrialized countries and a rising incidence in industrialized countries as
      well. Its close association with chronic liver diseases and liver cirrhosis
      represents a significant challenge in its treatment. A front-line systemic
      treatment for unresectable cases of HCC (sorafenib) was identified only in 2007.
      Following a decade of failed clinical trials with a wide range of drugs for
      second-line treatment, regorafenib proved its efficacy as a second-line treatment
      in 2016, when the randomized, placebo-controlled, phase III RESORCE trial
      demonstrated a meaningful increase in overall survival in the regorafenib
      treatment arm compared with the placebo arm (10.6 vs. 7.8 months). In this
      monograph we review the main preclinical and clinical findings in the trials
      assessing regorafenib for the treatment of HCC patients.

PMID- 29569658
TI  - An update on benznidazole for the treatment of patients with Chagas disease.
AB  - Chagas disease is a vector-borne, systemic and chronic parasitic infection caused
      by Trypanosoma cruzi with approximately 8 million cases worldwide. The treatment
      for acute phase of Chagas disease consists of benznidazole and nifurtimox,
      although this treatment combination falls short in terms of efficacy against
      chronic phases of infection. This review provides an update on benznidazole
      progress and approval by the U.S. Food and Drug Administration in 2017 for the
      treatment of Chagas disease along with its lacunae.

PMID- 29569659
TI  - Controversies regarding the cardiovascular effects of testosterone replacement
      therapy in older men.
AB  - Testosterone (T) levels decline with the advancement of age and have been
      associated with increased incidence of cardiovascular disease (CVD). Indeed,
      several epidemiologic and prospective cohort studies have suggested that low T
      levels (lower tertile or quartile) are associated with increased incidence of
      CVD, type 2 diabetes mellitus (T2DM), obesity and dyslipidemia. In contrast,
      correction of low T levels with testosterone replacement therapy (TRT) is
      associated with a decrease in the incidence of CVD, T2DM and dyslipidemia as has
      been demonstrated by several randomized, controlled trials as well as prospective
      cohort studies. However, recent studies have shown that TRT is associated with an
      increased incidence of adverse CV events and these studies have created a great
      controversy regarding the CV benefits of TRT. In order to get a better
      perspective on the current status of TRT, a focused MEDLINE and Cochrane database
      search of the recent English language literature between 2010 and 2017 was
      conducted and 29 pertinent papers were retrieved. The studies reviewed could not
      definitely confirm the beneficial or adverse CV effects of TRT. Therefore, on the
      basis of the current stage of knowledge, older male subjects with low T levels
      could continue to receive TRT, but this decision should be discussed with their
      physicians.

PMID- 29569660
TI  - The year's new drugs and biologics 2018: Part I.
AB  - This review presents the 113 new drugs and biologics that were approved or
      launched for the first time globally in 2017. Fifty-two new drugs and biologics
      reached their first markets worldwide in 2017. Seven of the new launches were
      first-in-class agents, meaning the first drug with a novel mechanism of action to
      be approved and launched anywhere in the world. In addition, 36 notable line
      extensions (i.e., new indications, new combinations and new formulations of
      previously marketed products) were introduced last year. The remaining 25
      products discussed in this article were approved for the first time during the
      year just passed, but had not yet been launched as of December 31, 2017. The
      United States was the most active market for new drugs, and oncology was the most
      active therapeutic group. Information on these new arrivals is covered in depth
      in part I of our annual review of the pharma and biotech industry.

PMID- 29569661
TI  - Evaluation of the Fluoride Releasing and Recharging Abilities of Various Fissure
      Sealants.
AB  - PURPOSE: To evaluate the fluoride release from different fissure sealants sold
      mainly in non-Western countries via a curve-fitting method, and to investigate
      the ability of these materials to be recharged with fluoride. MATERIALS AND
      METHODS: Four different fissure sealants which the manufacturers claim to release
      F- were tested; glass-ionomer cement Argecem (AC), the composite resins Fisskhim
      (FK), Fissulight (FL), Helioseal F (HF). Helioseal (HS), a composite resin not
      declared to release F, was used as a negative control. Of each material, 10 disks
      8.0 mm in diameter and 1.8 mm thick were produced. For fluoride measurements, a
      fluoride-ion specific electrode was used. On day 21, the specimens were recharged
      with fluoride by immersion in toothpaste slurry. Fluoride release was evaluated
      and statistically compared by fitting an exponential curve through the cumulative
      release values and statistically comparing curve parameters (t1/2, AUC and
      plateau value) among each other as well as before and after recharging. RESULTS:
      Two materials (AC and HF) released a considerable amount of F- in the first 3
      weeks after sample production. Furthermore, the increase of F- release after F-
      recharge was statistically significant (p < 0.05) for the materials AC, FL and
      HF, but not for FK and HS. CONCLUSION: Fluoride release of Fisskhim and
      Fissulight was negligible, while Helioseal F and Argecem noticeably released
      fluoride and thus can enhance the caries preventive effect of fissure sealants.
      Comparing release curve parameters simplifies statistical procedures.

PMID- 29569662
TI  - Photoconductivity enhancement and charge transport properties in ruthenium
      containing block copolymer/carbon nanotube hybrids.
AB  - Functional polymer/carbon nanotube (CNT) hybrid materials can serve as a good
      model for light harvesting systems based on CNTs. This paper presents the
      synthesis of block copolymer/CNT hybrids and the characterization of their
      photocurrent responses by both experimental and computational approaches. A
      series of functional diblock copolymers was synthesized by reversible addition
      fragmentation chain transfer polymerizations for the dispersion and
      functionalization of CNTs. The block copolymers contain photosensitizing
      ruthenium complexes and modified pyrene-based anchoring units. The photocurrent
      responses of the polymer/CNT hybrids were measured by photoconductive atomic
      force microscopy (PCAFM), from which the experimental data were analyzed by
      vigorous statistical models. The difference in photocurrent response among
      different hybrids was correlated to the conformations of the hybrids, which were
      elucidated by molecular dynamics simulations, and the electronic properties of
      polymers. The photoresponse of the block copolymer/CNT hybrids can be enhanced by
      introducing an electron-accepting block between the photosensitizing block and
      the CNT. We have demonstrated that the application of a rigorous statistical
      methodology can unravel the charge transport properties of these hybrid materials
      and provide general guidelines for the design of molecular light harvesting
      systems.

PMID- 29569663
TI  - Optimal and robust control of quantum state transfer by shaping the spectral
      phase of ultrafast laser pulses.
AB  - Achieving fast and efficient quantum state transfer is a fundamental task in
      physics, chemistry and quantum information science. However, the successful
      implementation of the perfect quantum state transfer also requires robustness
      under practically inevitable perturbative defects. Here, we demonstrate how an
      optimal and robust quantum state transfer can be achieved by shaping the spectral
      phase of an ultrafast laser pulse in the framework of frequency domain quantum
      optimal control theory. Our numerical simulations of the single dibenzoterrylene
      molecule as well as in atomic rubidium show that optimal and robust quantum state
      transfer via spectral phase modulated laser pulses can be achieved by
      incorporating a filtering function of the frequency into the optimization
      algorithm, which in turn has potential applications for ultrafast robust control
      of photochemical reactions.

PMID- 29569664
TI  - A new 'sticking' coating method for the in situ formation of nanofiber networks
      on micrometer to millimeter-sized surfaces.
AB  - A simple versatile method to form a nanofiber coating in situ on micrometer to
      millimeter-sized surfaces is developed. A fiber-filled porous sheet is designed
      by electrospinning a dense polymer solution on a patterned PET/aluminum alloy
      collector. By sticking the small area surface onto a fiber-filled porous sheet, a
      nanofiber-coated small area surface is obtained, which overcomes conventional
      nanofiber coating difficulties.

PMID- 29569665
TI  - The good, the bad, and the ugly - controlling singlet oxygen through design of
      photosensitizers and delivery systems for photodynamic therapy.
AB  - Singlet oxygen, although integral to photodynamic therapy, is notoriously
      uncontrollable, suffers from poor selectivity and has fast decomposition rates in
      biological media. Across the scientific community, there is a conscious effort to
      refine singlet oxygen interactions and initiate selective and controlled release
      to produce a consistent and reproducible therapeutic effect in target tissue.
      This perspective aims to provide an insight into the contemporary design
      principles behind photosensitizers and drug delivery systems that depend on a
      singlet oxygen response or controlled release. The discussion will be accompanied
      by in vitro and in vivo examples, in an attempt to highlight advancements in the
      field and future prospects for the more widespread application of photodynamic
      therapy.

PMID- 29569666
TI  - Circulating tumor DNA and liquid biopsy: opportunities, challenges, and recent
      advances in detection technologies.
AB  - Cell-free DNA (cfDNA) refers to short fragments of acellular nucleic acids
      detectable in almost all body fluids, including blood, and is involved in various
      physiological and pathological phenomena such as immunity, coagulation, aging,
      and cancer. In cancer patients, a fraction of hematogenous cfDNA originates from
      tumors, termed circulating tumor DNA (ctDNA), and may carry the same mutations
      and genetic alterations as those of a primary tumor. Thus, ctDNA potentially
      provides an opportunity for noninvasive assessment of cancer. Recent advances in
      ctDNA analysis methods will potentially lead to the development of a liquid
      biopsy tool for the diagnosis, prognosis, therapy response monitoring, and
      tracking the rise of new mutant sub-clones in cancer patients. Over the past few
      decades, cancer-specific mutations in ctDNA have been detected using a variety of
      untargeted methods such as digital karyotyping, personalized analysis of
      rearranged ends (PARE), whole-genome sequencing of ctDNA, and targeted approaches
      such as conventional and digital PCR-based methods and deep sequencing-based
      technologies. More recently, several chip-based electrochemical sensors have been
      developed for the analysis of ctDNA in patient samples. This paper aims to
      comprehensively review the diagnostic, prognostic, and predictive potential of
      ctDNA as a minimally invasive liquid biopsy for cancer patients. We also present
      an overview of current advances in the analytical sensitivity and accuracy of
      ctDNA analysis methods as well as biological and technical challenges, which need
      to be resolved for the integration of ctDNA analysis into routine clinical
      practice.

PMID- 29569667
TI  - A 3D-printed flow distributor with uniform flow rate control for multi-stacked
      microfluidic systems.
AB  - In the scale-up of chemical production in a microfluidic system, it is
      challenging to prevent flow maldistribution from a single inlet into stacked
      multiple microchannel exits. In the present study, a compact flow distributor
      equipped with a fluidic damper is developed by computational fluid dynamics (CFD)
      along with experimental validation. A microfluidic flow distributor, which is
      equipped with an optimized fluidic damper and consists of 25 exit channels, is
      fabricated as an integrated body using a digital light processing (DLP) type 3D
      printer. The 3D printed flow distributor with a CFD-optimized fluidic damper is
      found to achieve a low maldistribution factor (MF) of 2.2% for the average flow
      rate over 25 exit channels while inducing only a minor increment (<6%) in the
      pressure drop. A generalized manual is proposed for the design of optimal flow
      distributors with different scale-up dimensions. Using the manual, an optimal
      flow distributor with 625 stacked microchannels with a MF of only 1.2% is
      successfully designed. It is expected that the design manual and the rapid
      printing platform will allow the efficient development of multi-channel stacked
      micro-devices such as those in drug delivery and energy conversion systems where
      equidistribution of fluid flow is highly demanded.

PMID- 29569668
TI  - Theranostic micelles based on upconversion nanoparticles for dual-modality
      imaging and photodynamic therapy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is frequently metastatic once diagnosed and less
      likely to respond to curative surgery, emphasizing the need for the development
      of more sensitive and effective diagnostic and therapeutic strategies. Epithelial
      cell adhesion molecule (EpCAM) is deemed as the biomarker of cancer stem cells
      (CSCs), which are mainly responsible for the recurrence, metastasis and prognosis
      of HCC. In this study, we discuss the use of mitoxantrone (MX), an antitumor drug
      and a photosensitizer, for designing upconversion nanoparticle-based micelles
      grafted with the anti-EpCAM antibody, for dual-modality magnetic
      resonance/upconversion luminescence (MR/UCL)-guided synergetic chemotherapy and
      photodynamic therapy (PDT). The obtained micelles exhibit good biocompatibility,
      high specificity to HCC cells and superior fluorescent/magnetic properties in
      vitro. In vivo results demonstrate that the targeted micelles exhibited much
      better MR/UCL imaging qualities compared to the nontargeted micelles after the
      intravenous injection. More importantly, PEGylated UCNP micelles loaded with MX
      and grafted with anti-EpCAM antibody, denoted as anti-EpCAM-UPGs-MX, showcased
      the most effective synergetic antitumor efficacy compared with other treatment
      groups both in vitro and vivo. The remarkable antitumor effect, coupled with
      superior simultaneous dual-modality MR/UCL imaging as well as good
      biocompatibility and negligible toxicity, makes the UPG micelles promising for
      future translational research in HCC diagnosis and therapy.

PMID- 29569670
TI  - Building expanded structures from tetrahedral DNA branching elements, RNA and TMV
      protein.
AB  - By combining both chemical and enzymatic ligation with procedures guiding the
      self-assembly of nanotubular tobacco mosaic virus (TMV)-like particles (TLPs),
      novel nucleoprotein structures based on DNA-terminated branching elements, RNA
      scaffolds and TMV coat protein (CP) are made accessible. Tetrahedral
      tetrakis(hydroxybiphenyl)adamantane cores with four 5'-phosphorylated
      dinucleotide arms were coupled to DNA linkers by chemical ligation. The resulting
      three-dimensional (3D) branching elements were enzymatically ligated to the 3'
      termini of RNA scaffolds either prior to or after the RNAs' incorporation into
      TLPs. Thus, architectures with interconnected nanotube domains in two different
      length classes were generated, each containing 70 CP subunits per 10 nm length.
      Short TMV origin-of-assembly-containing RNA scaffolds ligated to the DNA allowed
      the growth of protein-coated 34 nm tubes on the terminal RNA strands in situ.
      Alternatively, 290 nm pre-fabricated tubes with accessible RNA 3' termini,
      attained by DNA blocking elements hybridized to the RNAs, were ligated with the
      branched cores. Both approaches resulted in four-armed nanoobjects, demonstrating
      a so far unique combination of organic synthesis of branching elements, enzymatic
      modifications, nucleic acid-based scaffolding and RNA-guided and DNA-controlled
      assembly of tubular RNA-encapsidating protein domains, yielding a novel class of
      3D nucleoprotein architectures with polyvalent protein elements. In the long
      term, the production route might give rise to supramolecular systems with complex
      functionalities, installed via the orthogonal coupling of effector molecules to
      TLP domains.

PMID- 29569669
TI  - Carbon chain shape selectivity by the mouse olfactory receptor OR-I7.
AB  - The rodent OR-I7 is an olfactory receptor exemplar activated by aliphatic
      aldehydes such as octanal. Normal alkanals shorter than heptanal bind OR-I7
      without activating it and hence function as antagonists in vitro. We report a
      series of aldehydes designed to probe the structural requirements for aliphatic
      ligand chains too short to meet the minimum approximate 6.9 A length requirement
      for receptor activation. Experiments using recombinant mouse OR-I7 expressed in
      heterologous cells show that in the context of short aldehyde antagonists, OR-I7
      prefers binding aliphatic chains without branches, though a single methyl on
      carbon-3 is permitted. The receptor can accommodate a surprisingly large number
      of carbons (e.g. ten in adamantyl) as long as the carbons are part of a
      conformationally constrained ring system. A rhodopsin-based homology model of
      mouse OR-I7 docked with the new antagonists suggests that small alkyl branches on
      the alkyl chain sterically interfere with the hydrophobic residues lining the
      binding site, but branch carbons can be accommodated when tied back into a
      compact ring system like the adamantyl and bicyclo[2.2.2]octyl systems.

PMID- 29569671
TI  - Spontaneous rolling-up and assembly of graphene designed by using defects.
AB  - The inverse Stone-Wales defect is a typical defect in graphene, which causes
      local bumps and local deformation in graphene sheets. Our molecular dynamics
      simulations show that the spontaneous rolling up of graphene sheets can be
      induced by orderly distributed inverse Stone-Wales defect bumps, when defective
      graphene is cut into small strips. This spontaneous process is mainly dominated
      by the defect density and tailored graphene size. When the tailored length is
      longer than the upper threshold length, graphene sews up as a curly one
      dimensional structure: heart-shaped nanotube. For medium length graphene (the
      length is in between the lower threshold value and upper threshold value), the
      results reveal that graphene finally curls into a completely or incompletely
      stitched nanotube similar to a cylindrical shell. This spontaneous process is
      produced by a high-frequency damped vibration accompanied by elastic and
      viscoelastic deformation in defective graphene. Thus, the properties of vibration
      are further investigated for graphene that has the tailored length shorter than
      the lower threshold length. This kind of graphene gradually forms a curved
      nanoribbon rather than a nanotube. It is also found that the bending rigidity of
      defective graphene is larger than that of pristine graphene.

PMID- 29569672
TI  - Recent advances in the nanoengineering of electrocatalysts for CO2 reduction.
AB  - Emissions of CO2 from fossil fuel combustion and industrial processes have been
      regarded as the dominant cause of global warming. Electrochemical CO2 reduction
      (ECR), ideally in aqueous media, could potentially solve this problem by the
      storage of energy from renewable sources in the form of chemical energy in fuels
      or value-added chemicals in a sustainable manner. However, because of the
      sluggish reaction kinetics of the ECR, efficient, selective, and durable
      electrocatalysts are required to increase the rate this reaction. Despite
      considerable progress in using bulk metallic electrodes for catalyzing the ECR,
      greater efforts are still needed to tackle this grand challenge. In this Review,
      we highlight recent progress in using nanoengineering strategies to promote the
      electrocatalysts for the ECR. Through these approaches, considerable improvements
      in catalytic performance have been achieved. An outlook of future developments in
      applying and optimizing these strategies is also proposed.

PMID- 29569673
TI  - Collective motion of active Brownian particles with polar alignment.
AB  - We present a comprehensive computational study of the collective behavior
      emerging from the competition between self-propulsion, excluded volume
      interactions and velocity-alignment in a two-dimensional model of active
      particles. We consider an extension of the active brownian particles model where
      the self-propulsion direction of the particles aligns with the one of their
      neighbors. We analyze the onset of collective motion (flocking) in a low-density
      regime (10% surface area) and show that it is mainly controlled by the strength
      of velocity-alignment interactions: the competition between self-propulsion and
      crowding effects plays a minor role in the emergence of flocking. However, above
      the flocking threshold, the system presents a richer pattern formation scenario
      than analogous models without alignment interactions (active brownian particles)
      or excluded volume effects (Vicsek-like models). Depending on the parameter
      regime, the structure of the system is characterized by either a broad
      distribution of finite-sized polar clusters or the presence of an amorphous,
      highly fluctuating, large-scale traveling structure which can take a lane-like or
      band-like form (and usually a hybrid structure which is halfway in between both).
      We establish a phase diagram that summarizes collective behavior of polar active
      brownian particles and propose a generic mechanism to describe the complexity of
      the large-scale structures observed in systems of repulsive self-propelled
      particles.

PMID- 29569674
TI  - A distinctive transformation based diversity oriented synthesis of small ring
      carbocycles and heterocycles from biocatalytically derived enantiopure alpha
      substituted-beta-hydroxyesters.
AB  - A series of structurally novel small ring carbocyclic and heterocyclic molecules
      were accessed in an enantiopure fashion. The starting materials, alpha
      substituted-beta-hydroxyesters, were achieved through the biocatalytic dynamic
      kinetic resolution of parent beta-ketoesters in an excellent enantio and
      diastereocontrolled way. The active functional groups present in the starting
      precursor, were then tuned sequentially through certain key transformations
      (functional group interconversions; FGIs) to yield several small molecular
      scaffolds in a diverse way. Specific transformations such as halocyclization, ene
      yne metathesis, dipolar cycloaddition, Mitsunobu cyclization, ring closing
      metathesis and Pauson-Khand reactions were mainly applied to generate the
      diversity.

PMID- 29569675
TI  - Touching the theoretical capacity: synthesizing cubic LiTi2(PO4)3/C
      nanocomposites for high-performance lithium-ion battery.
AB  - A cubic LiTi2(PO4)3/C composite is successfully prepared via a simple
      solvothermal method and further glucose-pyrolysis treatment. The as-fabricated
      LTP/C material delivers an ultra-high reversible capacity of 144 mA h g-1 at 0.2C
      rate, which is the highest ever reported, and shows considerable performance
      improvement compared with before. Combining this with the stable cycling
      performance and high rate capability, such material has a promising future in
      practical application.

PMID- 29569676
TI  - A theoretical study on the oxidation of alkenes to aldehydes catalyzed by
      ruthenium porphyrins using O2 as the sole oxidant.
AB  - Density functional theory (DFT) calculations were used to study the ruthenium
      porphyrin-catalyzed oxidation of styrene to generate an aldehyde. The results
      indicate that two reactive oxidants, dioxoruthenium and monooxoruthenium-superoxo
      porphyrins, participate in the catalytic oxidation. In the mechanism, the
      resultant monooxoruthenium porphyrin acts in the tandem epoxide isomerization (E
      I) to selectively yield an aldehyde and generate a dioxoruthenium porphyrin,
      thereby triggering new oxidation reaction cycles. In this calculation, several
      key elements responsible for the observed oxidative ability have been established
      by using Frontier molecular orbital (FMO) theory, natural bond orbital (NBO)
      analysis, etc., which include the reaction energy, the spin exchange effect, the
      spin-state conversion process, and the energy level of the lowest unoccupied
      molecular orbitals (LUMOs) of the reactive oxidants. The comparative oxidative
      abilities of the ruthenium-oxo/superoxo compounds with different axial ligands
      are also investigated. The results suggest that the ruthenium-oxo/superoxo
      species featuring a chlorine axial ligand is more reactive than that substituted
      with oxygen. This tuneable reactivity can be understood when considering the
      different electronic characters of the two ligands and the effective atomic
      number rule (EAN).

PMID- 29569677
TI  - Monte Carlo simulations of weak polyelectrolyte microgels: pH-dependence of
      conformation and ionization.
AB  - In this study, we investigated the effect of pH on single weak acidic
      polyelectrolyte microgels under salt-free conditions with (i) varying microgel
      concentration, (ii) varying content of acidic groups and (iii) different
      crosslinking densities using Monte Carlo simulations under explicit consideration
      of the protonation/deprotonation reaction. We assessed both global properties,
      such as the degree of ionization, the degree of swelling and the counterion
      distribution, and local properties such as the radial network ionization profile
      and the ionization along the polymer chains as a function of pH. We found a
      pronounced suppression of the pH-dependent ionization of the microgels, as
      compared to the ideal titration behavior and a shift of the titration curve to a
      higher pH originating in the proximity of acidic groups in the microgel. In
      contrast to macroscopic gels, counterions can leave the microgel, resulting in an
      effective charge of the network, which hinders the ionization. A decreasing
      microgel concentration leads to an increased effective charge of the microgel and
      a more pronounced shift of the titration curve. The number of acidic groups
      showed only a weak effect on the ionization behavior of the microgels. For two
      different microgels with different crosslinking densities, similar scaling of the
      gel size was observed. A distinct transition from an uncharged and unswollen to a
      highly charged and expanded polymer network was observed for all investigated
      microgels. The degree of swelling mainly depends on the degree of ionization. An
      inhomogeneous distribution of the degree of ionization along the radial profile
      of the microgel was found.

PMID- 29569678
TI  - Dynamic alterations of hepatocellular function by on-demand elasticity and
      roughness modulation.
AB  - Temperature-responsive cell culture substrates reported here can be dynamically
      programmed to induce bulk softening and surface roughness changes in the presence
      of living cells. Alterations in hepatocellular function following temporally
      controlled substrate softening depend on the extent of stiff mechanical priming
      prior to user-induced material transition.

PMID- 29569679
TI  - The success of endotracheal intubation with a modified laryngoscope using night
      vision goggles.
AB  - BACKGROUND: Endotracheal intubation (ETI) procedure in the combat area differs
      from prehospital trauma life support procedures because of the danger of gunfire
      and the dark environment. We aimed to determine the success, difficulty degree,
      and duration of ETI procedures with a classical laryngoscope (CL) in a bright
      room and with a modified laryngoscope (ML) model in a dark room. METHODS: All
      interventions were performed by a combatant medical staff of 10 members. We
      developed an ML model to obtain a tool that can be used in combination with night
      vision goggles (NVGs) to perform ETI at night. The procedures were performed
      using a CL with the naked eye in a bright room and using a ML with NVGs in a dark
      room. The ETI procedure that used the ML was performed by engaging and locking
      the blade on the handle either in the mouth (ML-IM) or outside of the mouth (ML
      OM). RESULTS: The mean completion times for the ETI procedures, namely Day-CL, ML
      OM+NVG, and ML-IM+NVG, performed by the operators were 14.46, 26.9, and 32.38 s,
      respectively. The ML-OM+NVG and ML-IM+NVG procedures were significantly longer
      than the Day-CL procedure (p<0.05). The ML-IM+NVG procedure was significantly
      longer than the ML-OM+NVG procedure (p<0.05). All ETI procedures were found to be
      100% successful. The Day-CL procedure was easier than the ML-OM+NVG and ML-IM+NVG
      procedures (p>0.05). CONCLUSION: The ETI procedure is applicable using NVGs in
      dark conditions on the battlefield. Medical interventions performed using NVGs in
      the dark should be a part of the basic training provided in tactical emergency
      medicine.

PMID- 29569680
TI  - Successful non-operative management of blunt abdominal trauma in highly selective
      cases: A safe and effective choice.
AB  - BACKGROUND: The non-operative management (NOM) of abdominal injuries has gained
      wide acceptance over the last few decades. The present study evaluated the
      efficacy of NOM in blunt abdominal trauma (BAT) at a regional Hellenic hospital.
      METHODS: We analyzed the results of a pre-decided treatment protocol, which was
      applied to all patients hospitalized for BAT, from 2008 to 2015. The protocol
      proposed NOM in hemodynamically stable patients with no signs of peritonitis. The
      demographic characteristics, type of injury, injured organ(s), type of management
      (operative vs. non-operative), Injury Severity Score (ISS), morbidity, mortality
      rates, and health costs were evaluated. RESULTS: One hundred and forty-six
      patients hospitalized for BAT at our department were included. Among them, 49
      were operated and 97 were subjected to NOM. Although ISS was significantly higher
      in the surgical group, the severity of injuries in liver, spleen, and kidneys was
      not different between the two groups. Surprisingly, no case subjected to NOM
      required a conversion to operative management, which may probably be because of
      the strict inclusion criteria for NOM. CONCLUSION: Patients with hemodynamic
      stability and normal physical examination may be non-operatively treated,
      independent of the grade of injury, in highly selective cases. ISS score is an
      independent risk factor for surgical treatment.

PMID- 29569681
TI  - Can serum soluble urokinase plasminogen activator receptor be an effective marker
      in the diagnosis of appendicitis and differentiation of complicated cases?
AB  - BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a new
      biomarker of inflammation level. The aim of the study was to evaluate whether
      suPAR levels could be useful to detect acute appendicitis and to differentiate
      uncomplicated appendicitis (UA) from complicated appendicitis (CA). METHODS: We
      prospectively studied 105 patients consisting of 40 UA cases, 40 CA cases, and 25
      control patients. Blood samples were collected to measure suPAR level, C-reactive
      protein level, leukocyte counts, neutrophil counts, and neutrophil percentages
      preoperatively. RESULTS: Median values of suPAR level, C-reactive protein level,
      leukocyte counts, neutrophil counts, and neutrophil percentages in UA and CA were
      significantly higher than control patients. suPAR levels of the UA and CA groups
      showed a statistically significant difference (p=0.016). CONCLUSION: The current
      study demonstrated that serum suPAR concentrations can be helpful in
      differentiating CA from UA and in diagnosing acute appendicitis.

PMID- 29569682
TI  - Features and treatment of gas-forming synergistic necrotizing cellulitis: a nine
      year retrospective study.
AB  - BACKGROUND: As many doctors know little about gas-forming synergistic necrotizing
      cellulitis, we retrospectively explored it in our study. METHODS: Totally, 30
      patients diagnosed with gas-forming synergistic necrotizing cellulitis between
      November 2006 and September 2015 were included. They were divided into two
      groups: open drainage group (19 patients) and aggressive debridement group (11
      patients). Retrospectively analyzed data comprised demographic characteristics,
      APACHE II scores, pathogen culture results, bleeding amount during the operation,
      white blood cell count, length of hospital stay and recovery. RESULTS: The
      mortality rate was 26% in the open drainage group and 73% in the aggressive
      debridement group (p=0.023). There was no statistical difference in the APACHE II
      score before treatment between the open drainageand aggressive debridement groups
      (16.6+/-4.5 vs 18.1+/-7.5, p=0.511). The APACHE II score was significantly higher
      after treatment in the aggressive debridement group (14.2+/-5.8 score vs 20.1+/
      9.1, p=0.038). There were no statistical differences in the white blood count
      cell before and after treatment (13.49 * 109+/-5.05*109 cells/L vs 17.46*109+/
      6.94*109 cells/L, p=0.082; 10.37*109+/-3.54*109 cells/L vs 15.47*109 +/-7.51*109
      cells/L, p=0.055; respectively). The bleeding amount during the operation was
      significantly more in the aggressive debridement group (315+/-112 ml vs 105+/-45
      ml, p<0.001. CONCLUSION: For treating gas-forming synergistic necrotizing
      cellulitis, performing open drainage as early as possible isthe most important
      procedure after admission.

PMID- 29569683
TI  - Computed tomography use in minor head injury: attitudes and practices of
      emergency physicians, neurosurgeons, and radiologists in Turkey.
AB  - BACKGROUND: We aimed to determine the attitudes and practices of emergency
      physicians (EPs), neurosurgeons, and radiologists in Turkey regarding computed
      tomography (CT) use for adults with minor head injury (MHI). METHODS: This cross
      sectional study was conducted between August 2015 and October 2016 after
      obtaining the approval of the institutional ethical committee. The purpose of
      this study was disclosed to the participants prior to beginning the survey. The
      study was performed conducting a questionnaire via e-mail on three groups of
      participants including EPs, neurosurgeons, and radiologists. Participants
      comprised academic staff at university hospitals as well as department chiefs,
      specialists, and residents working at university, government, and private
      hospitals, all of whom are in charge of evaluating MHI patients. RESULTS: A total
      of 607 participants including 201 (33.1%) EPs, 179 (29.5%) neurosurgeons, and 227
      (37.4%) radiologists responded to the survey; 31% of the participants reported
      awareness and 27.3% reported use of head CT rules in MHI. Awareness and use of
      the rules were most prominent in EPs group, while the lowest rates were observed
      in radiologists group (p<0.01). The leading factors inhibiting the use of head CT
      rules in MHI stated by EPs were medicolegal anxiety (73.6%), expectations of
      patients and/or patient relatives (72.6%), and time constraints (44.3%). The
      leading factors stated by neurosurgeons were medicolegal anxiety (60.9%) and
      expectations of patient and/or patient relatives (46.4%); "not being consulted in
      the decision-making process to obtain CT in MHI" (65.6%) and medicolegal anxiety
      (49.8%) were the leading factors stated by radiologists. CONCLUSION: The results
      of our study show that many physicians in Turkey do not have favorable attitudes
      regarding head CT rules in MHI. Medicolegal anxiety, expectations of patient
      and/or patient relatives, time constraints, wide availability of CT, and lack of
      adequate education on radiation protection or on patient dose from imaging are
      the common reasons for this practice pattern.

PMID- 29569684
TI  - Media-based clinical research on selfie-related injuries and deaths.
AB  - BACKGROUND: The incidence of taking selfies and sharing them on social media as
      well as selfie-related behaviors is increasing, particularly among young people,
      possible leading to selfie-related trauma. Therefore, we performed this clinical
      study to draw attention to selfie-related injuries and deaths. METHODS: We
      analyzed 159 selfie victims from 111 events or accidents, which were reported in
      the media sources. We evaluated vital results, demography, rhythmicity,
      preferences, event or accident types, selfie-related risk factors, affected body
      regions of victims with causes of injury, and death. RESULTS: We found that the
      majority of selfie victims were students. Selfie-related injuries and deaths were
      reported most frequently in India, the US, and Russia. The most preferred site of
      taking selfies was the edge of the cliff. The most frequently reported event or
      accident type was falling from a height. Mostly multiple body parts were affected
      in selfie-related injuries and deaths. The most frequent causes of selfie-related
      deaths were multitrauma and drowning. CONCLUSION: Selfie-related injuries and
      deaths have increased in the past years. Particularly, teenagers and young adults
      are at high risk for selfie-related traumas and deaths; therefore, drastic
      measures should be taken to reduce their incidence.

PMID- 29569685
TI  - Importance of knowledge of the management of traumatic dental injuries in
      emergency departments.
AB  - BACKGROUND: Hospital emergency departments (EDs) are confronted with managing
      dental emergencies of both traumatic and non-traumatic origin. However, the
      literature suggests inadequate knowledge of the management of traumatic dental
      injuries (TDIs) among medical professionals. The aim of this study was to
      investigate the knowledge and attitudes regarding management of TDIs among
      Istanbul ED physicians. METHODS: Surveys were distributed to emergency
      departments (ED) directors and their physicians. The survey contained questions
      about their characteristics and tested their knowledge of managing dental trauma.
      RESULTS: A total of 126 surveys (13 ED directors and 113 physicians) were
      returned and included in the analysis. ED physician's knowledge of the
      appropriate management of crown fractures and avulsion was generally good
      (p=0.221), but poor for luxation injuries (p=0.0001). Physicians were more likely
      to have a better knowledge about permanent teeth than about primary teeth
      (p=0.027). CONCLUSION: Education, monitoring, improved availability of resources,
      and disciplinary measures in cases of poor compliance are necessary to improve
      TDI management in hospitals, especially among physicians.

PMID- 29569686
TI  - Spiked railing penetration that causes injuries in the upper extremities of
      children.
AB  - BACKGROUND: Children have a curiosity for climbing walls, stairs, and railings
      and have an increased risk of falling. Here, we report our experience with
      railings causing injuries by penetrating the upper extremities, and aim to call
      attention to spiked railing injuries in children. METHODS: We report on five
      children with a mean age of 8.8. All of the children were male. The penetrating
      railing parts were removed in a surgical room. RESULTS: The injured structures
      repaired immediately were as follows: flexor digitorum profundus tendon, A4
      pulley, volar plate of the distal interphalangeal joint, radial digital nerve,
      ulnar digital artery, and radial digital artery. CONCLUSION: Spiked railings can
      lead to significant injury that requires further exploration. Boys particularly
      are at risk, and parents should be alert regarding these type of injuries. We
      recommend a standard regulation for fence erection, and we wish to warn owners of
      this type of fence regarding probable legal sanctions.

PMID- 29569687
TI  - Mortality in Code Blue; can APACHE II and PRISM scores be used as markers for
      prognostication?
AB  - BACKGROUND: Code blue (CB) is an emergency call system developed to respond to
      cardiac and respiratory arrest in hospitals. However, in literature, no scoring
      system has been reported that can predict mortality in CB procedures. In this
      study, we aimed to investigate the effectiveness of estimated APACHE II and PRISM
      scores in the prediction of mortality in patients assessed using CB to
      retrospectively analyze CB calls. METHODS: We retrospectively examined 1195
      patients who were evaluated by the CB team at our hospital between 2009 and 2013.
      The demographic data of the patients, diagnosis and relevant de-partments,
      reasons for CB, cardiopulmonary resuscitation duration, mortality calculated from
      the APACHE II and PRISM scores, and the actual mortality rates were
      retrospectively record-ed from CB notification forms and the hospital database.
      RESULTS: In all age groups, there was a significant difference between actual
      mortality rate and the expected mortality rate as estimated using APACHE II and
      PRISM scores in CB calls (p<0.05). The actual mortality rate was significantly
      lower than the expected mortality. CONCLUSION: APACHE and PRISM scores with the
      available parameters will not help predict mortality in CB procedures. Therefore,
      novels scoring systems using different parameters are needed.

PMID- 29569688
TI  - Surgical treatment of displaced intraarticular calcaneus fractures using
      anatomical lateral frame plate.
AB  - BACKGROUND: The present study evaluated the results obtained from the anatomical
      lateral frame plate treatment of displaced intraarticular calcaneus fractures.
      METHODS: Overall, 14 displaced intraarticular fractures of 13 patients (3
      females, 10 males; Mean age, 37.5 years) were included in the present study.
      Surgery was performed using widened lateral approach and supported by auto grafts
      following joint line reduction in all patients. They were then fixated by
      anatomical lateral frame plate. All the joints were stabilized by casting after
      the operation. All patients were prescribed controlled and full weight bearing at
      6-8th and 12th weeks, respectively. RESULTS: Mean follow-up of patients was 28
      months. The fractures were classified according to Sanders system. Clinical
      scoring of the patients was performed according to American Orthopaedic Foot and
      Ankle Society, Creighton-Nebraska, and Maryland systems. According to these
      systems, the mean scores of the patients were 83.7, 75.7, and 88.5 respectively.
      CONCLUSION: In the present study, we have defined the results of anatomical
      lateral frame plate treatment in patients with displaced intraarticular calcaneus
      fractures. We have obtained clinically and radiologically satisfactory results
      with the anatomical compatibility of plate to the lateral surface of the
      calcaneus.

PMID- 29569689
TI  - Open reduction and internal fixation in AO type C distal humeral fractures using
      olecranon osteotomy: Functional and clinical results.
AB  - BACKGROUND: To investigate the outcomes of patients undergoing open reduction and
      internal fixation with olecranon osteotomy due to AO type13C fractures of the
      distal humerus. METHODS: Data of 39 patients (mean age, 44.7 years; males, 56.4%)
      undergoing surgery with the diagnosis of AO type 13C distal humeral fractures
      were retrospectively evaluated. Patients' demographic characteristics, medical
      history, and radiological and functional outcomes were recorded. The patients
      were evaluated at the final follow-up according to the Mayo Elbow Performance
      Index (MEPI). RESULTS: The mean degrees of flexion and extension loss were 102.2
      degrees (range, 60-120 degrees) and 11.4 degrees (range, 0-25 degrees),
      respectively, at the final follow-up. According to the MEPI score, outcomes were
      excellent in seven, good in 12, fair in 13, and poor in seven patients. All
      patients achieved a radiological union of the fracture site within the first
      postoperative six months. It was found that the loss of extension was more
      severe, the range of flexion was decreased, and the mean MEPI score was lower in
      the patients with type C3 fractures than in those with type C1 and type C2
      fractures. No significant difference was determined between fixation techniques
      (tension band vs. cannulated screw) regarding the functional outcomes.
      CONCLUSION: Our results revealed better prognosis in AO type C1 and type C2
      fractures than in AO type C3 fractures and no different effects of two fixation
      techniques in olecranon osteotomy on the outcomes.

PMID- 29569690
TI  - Fixation of rotationally unstable extracapsular proximal femoral fractures.
AB  - BACKGROUND: It was thought that the AO types A1.2 and A1.3 fractures are
      rotationally stable; however, it revealed instability when fixed using the
      dynamic hip screw. Therefore, we hypothesized that these fractures should be
      treated as rotationally unstable. METHODS: A series of 83 fractures of the AO
      types A1, A2, and B2.1 were treated using dynamic hip screw with derotation screw
      (DHS/DRS) composite and then prospectively followed for 24 months. Adequacy of
      reduction and fixation were immediately assessed after surgery, and fracture
      collapse was assessed at six months or when fractures healed. To investigate the
      feasibility of our hypothesis, fractures were classified into two groups: 1) the
      inevitably unstable group (IUG) included the AO types A1.1, A2.1, A2.2, A2.3, and
      B2.1 fractures and 2) the potentially unstable group (PUG) included the AO types
      A1.2 and A1.3 fractures. The results were statistically analyzed. RESULTS:
      Adequate reduction was achieved in 77 and adequate fixation in 71 fractures. All
      fractures healed in a mean time of 13.5 weeks, and the amount of the fracture
      collapse averaged 5.8 mm. Equalization of the lower limbs was achieved in 66
      patients, and hip motion range equalized the healthy contralateral in 80
      patients. Re-operation was performed in one case with AO type A1.2. Comparison of
      IUG and PUG using the outcomes revealed insignificant differences. CONCLUSION:
      Using the DHS/DRS composite, anatomical features of the proximal femoral end were
      restored and maintained during the follow-up period. Insignificant differences
      between outcomes of IGU and PGU render the addition of the AO types A1.2 and A1.3
      to the rotationally unstable fractures reasonable.

PMID- 29569691
TI  - Traumatic evisceration after blunt trauma in a 20-month-old boy.
AB  - Blunt traumatic evisceration is extremely rare. We describe the case of a 20
      month-old boy with stomach and small and large intestine evisceration after blunt
      trauma. Immediate laparotomy and surgical repair were performed. There was no
      injury, other than a small hole in the mesentery. The bowels were drained into
      the abdominal cavity, and the skin was closed. The patient recovered well.

PMID- 29569692
TI  - Intestinal nonrotation and left-sided perforated appendicitis.
AB  - Acute appendicitis is the most common cause of acute abdominal pain, requiring
      emergency surgery. Approximately one third of cases have pain unexcepted location
      due to its various anatomical location. Acute appendicitis is a very rare cause
      of left lower quadrant pain; if it occurs, a few congenital anomalies should be
      considered such as Situs Inversus totalis and Midgut Malrotation (MM). MM is a
      rare congenital anomaly; it occurs due to error in process of rotation or
      fixation of intestines around the superior mesenteric vessels and it refers to
      nonrotation or incomplete rotation of intestines. Here we report a case who
      presented with left lower abdominal pain and was diagnosed with acute perforated
      appendicitis with intestinal nonrotation. Clinicians should be aware that
      intestinal nonrotation may be presented with left lower quadrant pain and
      complicated by acute appendicitis.

PMID- 29569693
TI  - Acute arterial occlusion due to vascular closure device: A report of two cases.
AB  - Vascular closure devices are frequently used after percutaneous arterial
      interventions to achieve hemostasis at the puncture site and facilitate early
      ambulation. Occasionally, complications have been reported with closure devices,
      such as hematoma, infection, arteriovenous fistula, pseudoaneurysm, and ischemia.
      This is a report of 2 cases of severe, acute-onset arterial occlusion and
      critical limb ischemia, one of which occurred in the upper limb following the use
      of a vascular closure device, and the required surgical treatment.

PMID- 29569695
TI  - Pneumothorax after a ventriculoperitoneal shunt placement: case report and review
      of the literature.
AB  - An 82-year-old woman underwent a ventriculoperitoneal (VP) shunt placement to
      treat hydrocephalus secondary to a right thalamic intracerebral hemorrhage.
      Pneumothorax and subcutaneous emphysema was noted 2 hours later. No respiratory
      distress was noted. A chest computed tomography scan revealed that the shunt tube
      had penetrated the diaphragm and entered the pleural space. The shunt tube
      penetrated the lung parenchyma and exited the pleural space via the third
      intercostal space. She underwent chest drainage and VP shunt reposition. The VP
      shunt functioned properly and no infection was noted. Bending the shunt passer
      slightly and keeping the passer tip pointed upward and palpable during its
      advancement may prevent this complication. It may be acceptable to leave the
      shunt tube in place after chest drainage for pneumothorax.

PMID- 29569694
TI  - Oxytocin for preventing injury due to testicular torsion/detorsion in rats.
AB  - BACKGROUND: We aimed to demonstrate the effectiveness of oxytocin on the testes
      for treating ischemia-reperfusion injury. METHODS: A total of 24 male Wistar
      albino rats weighing 250-320 g were used. The rats were randomized into three
      groups of eight rats. Group 1 was assessed as the control group. In Group 2 rats,
      testicular torsion was first performed, followed by testicular detorsion to
      induce reperfusion injury. In Group 3, following testicular torsion and
      detorsion, oxytocin was administered before inducing reperfusion. Testicular
      tissues were histologically evaluated, spermatogenic parameters were assessed
      using the Johnsen scoring system, and the mean Johnsen score was calculated.
      RESULTS: Histological tests revealed significantly different results between the
      testicular torsion group and the oxytocin-treated torsion and control groups as
      well as between the oxytocin-treated torsion group and the control and testicular
      torsion groups (p=0.010 and 0.012, respectively). Biochemical test results
      revealed that superoxide dismutase and glutathione peroxidase levels were
      significantly lower in Group 2 than in Group 1 (p=0.007 and 0.007, respectively).
      Malondialdehyde and nitric oxide levels were significantly lower in Group 3 than
      in Group 2 (p=0.017 and 0.014, respectively). CONCLUSION: These results indicate
      that oxytocin can be considered as an alternative agent for treating testicular
      torsion in clinical practice to minimize tissue damage.

PMID- 29569696
TI  - Association of rs2228570 Polymorphism of Vitamin D Receptor Gene with Lumbar
      Degenerative Disc Disease.
AB  - AIM: Lumbar degenerative disc disease (LDDD) is the most common cause of lower
      back pain (LBP) and sciatica. The vitamin D receptor (VDR) gene, which is located
      on chromosome 12 (12q12-q14), was the first gene reported to be potentially
      related to intervertebral degenerative disc disease risks. We conducted a case
      control study of a Turkish population and investigated the association between
      the VDR gene rs2228570 FokI polymorphism and the development of LDDD. MATERIAL
      AND METHODS: This was a prospective case-control study that included 45 patients
      with LDDD and 49 healthy individuals (control group). The clinical investigations
      of the LDDD patients consisted of neurological examinations, lumbar magnetic
      resonance imaging studies, visual analog scale (VAS) scores, and Oswestry
      Disability Index scores. The VDR gene rs2228570 FokI polymorphism was analyzed
      via a real-time polymerase chain reaction. RESULTS: We found that the individuals
      with the VDR GG genotype had a significantly increased risk of LDDD, while those
      with the AG genotype had a significantly decreased risk. In addition, the A
      allele may have a protective effect against LDDD in the Turkish population.
      Moreover, the VAS pain results showed that the GG genotype had a significantly
      higher score than the others. CONCLUSION: Our results suggested that the VDR
      rs2228570 AG genotype was at a decreased risk and the GG genotype was at an
      increased risk of LDDD in the Turkish population. Since genetic polymorphisms
      often show ethnic differences, further functional studies are needed to evaluate
      the genotype and phenotype correlations in large cohorts of various ethnicities.

PMID- 29569697
TI  - How Can Mesenchymal Stem Cells Penetrate the Blood Brain Barrier?

PMID- 29569698
TI  - Expression of microRNA-145, OCT4, and SOX2 in double primary endometrioid
      endometrial and ovarian carcinomas.
AB  - Double primary endometrioid endometrial and ovarian carcinomas (DPEEOCs) are the
      most common multiple gynecological carcinomas. In recent years, gene sequential
      comparison analysis has strongly supported the opinion that sporadic double
      endometrioid endometrial and ovarian cancers (DEEOCs) are clonally related in
      both primary and metastatic tumors. In order to find more clonal evidence for
      DPEEOC, we investigated cancer stem cells (CSCs). SOX2 and OCT4 are two common
      factors in CSCs. MicroRNA (miRNA)-145, a small non-coding RNA, has effects in
      regulating gene expression and tumorigenesis in CSCs. The aim of this study was
      to assess the involvements of SOX2, OCT4, and miRNA-145 in the tumorigenesis of
      DPEEOCs. In our study, twenty DPEEOC patients were chosen. Metastatic DEEOCs and
      normal endometrial and ovarian tissues were also included. The expression of
      miRNA-145 was detected by real-time quantitative PCR. Immunohistochemical
      staining was used to measure the expression of OCT4 and SOX2. The results showed
      that miRNA-145 expression was lower in DPEEOC endometrial tissues and higher in
      DPEEOC ovarian tissues compared to the corresponding normal tissues. Both SOX2
      and OCT4 were over-expressed in cancer tissues compared with that in normal
      tissues. MiRNA-145, SOX2, and OCT4 were expressed at similar levels in two cancer
      sites of a given DPEEOC or metastatic DEEOC sample. Besides, metastatic DEEOC
      sections expressed a higher level of SOX2 and OCT4 compared to the corresponding
      DPEEOC tissues. Together, these results support the clonality of DPEEOCs.
      Moreover, SOX2 and OCT4 may have some implication in DPEEOC and metastatic DEEOC
      diagnosis.

PMID- 29569699
TI  - The posterior epidural ligament in the thoracic region: a cadaveric and
      histological study.
AB  - The existence of posterior epidural ligaments (PEL) has been established in the
      lumbar region, but they have hitherto not been shown to exist in the thoracic
      vertebral column. Their identification is of clinical significance in respect to
      incidental durotomy and the circulation of cerebro-spinal fluid. Fourteen
      thoracic spine sections were dissected by cutting through the intervertebral disc
      and separating the ligamentum flavum from the vertebra above. The dural sheath
      was gently retracted anteriorly to identify macroscopic connections between the
      ligamentum flavum and the dura. Macroscopic connections observed were dissected
      out, retaining some dural sheath and ligamentum flavum. Histological staining
      with haematoxylin and eosin (H&E) and Miller's elastin stain was used to
      investigate cellular connections. Thoracic PELs were positively identified in
      five of the fourteen cadavers (35.7%). Histology showed similarities between the
      thoracic and lumbar PELs. Fifteen separate PELs were identified within these five
      thoracic sections. The thoracic PEL has sufficient tensile strength to present a
      risk to the integrity of the dural sheath during surgery, and surgeons should be
      aware of these connections when operating on the thoracic spine. PELs may also
      contribute to the circulation of CSF in the spinal subarachnoid space.

PMID- 29569700
TI  - A possible association between medial depression of mandibular ramus and maximum
      bite force.
AB  - BACKGROUND: Medial depression of the mandibular ramus (MDMR) is an anatomical
      depression with unknown etiology and described as a result of a slender
      mandibular ramus in the area of the mandibular notch. It is suggested that MDMR
      may be due to variations in muscle functions. The aim of this study is to compare
      the bite force of patients with and without MDMR detected on panoramic
      radiographs. MATERIAL AND METHODS: A hundred and ten patients (55 women and 55
      men; mean age 22.69 +/- 2.85 years) participated in this study. Patients were
      divided into two groups based on the prevalence of MDMR. Bite force of 55
      patients with MRMD and 55 patients without MDMR were determined using a bite
      force sensor. Non-parametric tests were used to assess differences between
      groups. RESULTS: Measurements showed statistically significant differences in
      bite force between genders (p=0.00) with men having higher values (535.98+187.85
      N) than women (363.59 + 139.56 N). The mean bite force in the sides with and
      without MDMR was 538.19 + 196.94 N and 396.22 + 157.69 N, respectively. There was
      a statistically significant difference between groups with and without MDMR
      (p=0.00). There was no statistically significant difference in bite force between
      groups according to Angle classification (p=0.581). CONCLUSIONS: This study
      suggests that the prevalence of MDMR may be an indicator of high muscle activity.
      Patients with MDMR should be carefully examined for the risk of relapse prior to
      any surgical intervention.

PMID- 29569701
TI  - Immunohistochemical characteristics of porcine intrahepatic nerves under
      physiological conditions and after Bisphenol A administration.
AB  - BACKGROUND: The neurochemistry of hepatic nerve fibers was investigated in large
      animal models after dietary exposure to the endocrine disrupting compound known
      as bisphenol A. MATERIALS AND METHODS: Antibodies against neuronal peptides were
      used to study changes in hepatic nerve fibers after exposure to bisphenol A (BPA)
      at varying concentrations using standard immunofluorescence techniques. The
      neuropeptides investigated were substance P (SP), galanin (GAL), pituitary
      adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated
      peptide (CGRP) and cocaine & amphetamine regulated transcript (CART).
      Immunoreactive nerve fibers were counted in multiple sections of the liver and
      among multiple animals at varying exposure levels. The data was pooled and
      presented as mean +/- SEM. RESULTS: It was found that all of the nerve fibers
      investigated showed upregulation of these neural markers after BPA exposure, even
      at exposure levels currently considered to be safe. These results show very
      dramatic increases in nerve fibers containing the above-mentioned neuropeptides
      and the altered neurochemical levels may be causing a range of pathophysiological
      states if the trend of over-expression is extrapolated to developing humans.
      CONCLUSIONS: This may have serious implications for children and young adults who
      are exposed to this very common plastic polymer, if the same trends are occurring
      in humans.

PMID- 29569702
TI  - An anatomical study of the origin, structure and insertion of the medial
      patellofemoral ligament.
AB  - BACKGROUND: Repair and reconstruction of the medial patellofemoral ligament
      (MPFL) has been undertaken for the treatment of patellar instability. For
      successful surgery detailed knowledge of the anatomy of the ligament is required.
      The aim of this study was to describe the origin, structure and insertion of the
      MPFL. MATERIALS AND METHODS: We studied cadaveric knees from 30 Chinese adults.
      We studied the origin, course and insertion of the MPFL. RESULTS: We found that
      the MPFL was composed of two main strands, superficial and deep. We also found
      that the insertion of the MPFL into the femur had three common patterns. All
      three were located between the adductor tubercle and the proximal part of
      superficial medial collateral ligament. CONCLUSIONS: We have added to the
      anatomical knowledge of the structure of the MPFL. Our study has implications for
      guiding bone tunnel positioning during MPFL reconstruction surgery. (Folia
      Morphol 2018; 77, 2: 356-361).

PMID- 29569703
TI  - Histopathological changes in the choroid plexus after traumatic brain injury in
      the rats: a histologic and immunohistochemical study.
AB  - Traumatic brain injury (TBI) is in part associated with the disruption of the
      blood-brain barrier. In this study, we analyzed the histopathological changes in
      E-cadherin and VEGF expression after traumatic brain injury in rats. The rats
      were divided into 2 groups as the control and the trauma groups. Sprague-Dawley
      rats were subjected to traumatic brain injury with a weight-drop device using 300
      g-1 m weight-height impact. After 5 days of traumatic brain injury, blood samples
      were taken under ketamine hydroxide anesthesia and biochemical analyzes were
      performed. The control and trauma groups were compared in terms of biochemical
      values. There was no change in glutathione (GSH) levels and blood brain barrier
      permeability. However, malondialdehyde (MDA) and myeloperoxidase activity (MPO)
      levels increased in the trauma group. In the histopathological examination,
      choroid plexus in the lateral ventricule, near the piamater membrane, was
      removed. In the traumatic group, some of epithelial cells were hyperplasic, some
      of were with local degeneration with peeled off from apical surface. In addition,
      we observed that congestion in capillary vessels and mononuclear cell
      infiltration around the vessels. After traumatic brain injury, the increase in
      vascular endothelial growth factor (VEGF) levels, vascular permeability, and
      interaction with VEGF receptors in endothelial cells lead to edema in the vessel
      wall. On the other hand, E-cadherin expression decreased in the tight-junction
      structures between epithelial cells and basal membrane, resulting in an increase
      in cerebrospinal fluid in the intervillous area.

PMID- 29569704
TI  - Morphology of cranial sutures and radiologic evaluation of the variations of
      intersutural bones.
AB  - BACKGROUND: As far as our literature searches showed us, morphological
      characteristics of cranium such as sutures, sutural bones and fontanelles had
      been examined from the skulls in the museums and dry specimens until now. As a
      modern method, 3D virtual remodeling of cranial bones by using MDCT-CTA can
      display in vivo morphological characteristics. In our study, we aimed to
      determine the presence and incidence of these morphological characteristics that
      can be clinically significant in our population, by using radiologic methods.
      MATERIALS AND METHODS: We examined head and neck regions of 185 patients via MDCT
      CTA. We evaluated radiologically detectable variations of the metopic sutures,
      lambda, bregma, asterion and pterion, which can be very easily confused with
      fractures. Additionally, the differences between the genders and incidence of
      coexistence of these variations were evaluated. RESULTS: According to our study,
      the incidence of persistent metopic suture was 8.1% and the incidence of lambda
      variations was 5.9%. Variations were most commonly encountered on the left
      asterion, and least commonly on the bregma and left pterion. In the evaluation of
      the coexistence of the parameters and combinations; the wormian bones located at
      the right and left asterions were detected. There were no statistically
      significant differences between genders. CONCLUSIONS: Variations of the sutures
      and sutural bones can be easily misdiagnosed with the fractures of related bony
      regions in unconscious patients with multiple traumas. During surgical
      interventions in these type of patients; surgeons must take this fact into
      consideration in order to make differential diagnosis of fractures and
      intersutural bone variations.

PMID- 29569705
TI  - Histological and immunohistochemical characterization of uterine adenocarcinoma
      in an Asian elephant (Elephas Maximus).
AB  - A 56 year old nulliparous female Asian elephant (Elephas maximus) living at the
      zoological garden of Naples (Italy), with a clinical history of recurrent colic,
      was found in agonal state and humane euthanasia was elected. At necropsy the
      uterine body was moderately increased in size and the lumen was reduced due to a
      poorly demarcated and infiltrative neoplasm. Furthermore, multiple, whitish, firm
      nodules were present in both lungs. Histological examination of the uterine mass
      revealed epithelial cells arranged in tubular or solid pattern infiltrating the
      endometrium and the muscular layer. Immunohistochemical examination showed
      immunoreactivity of neoplastic cells to estrogen receptors antibody. Pulmonary
      lesions were histologically and immunohistochemically superimposable to the
      epithelial uterine neoplasm. A definitive diagnosis of uterine adenocarcinoma
      with pulmonary metastases was made.

PMID- 29569706
TI  - Bilateral bifid mandibular canal: a case report using cone beam computed
      tomography.
AB  - The mandibular canal (MC) originates in the mandibular foramen and runs
      bilaterally through the mandibular ramus and body, ending in the mental foramen.
      One of the most common anatomical variations is bifid MC, the configurations of
      which have been classified into four categories and sub-categories. The
      prevalence of these variations depends on the imaging method used. Studies
      carried out in panoramic X-rays and Cone Beam Computed Tomography (CBCT) show
      prevalences varying between 1% and 20%. In this case report we present the
      finding of a bilateral bifid MC by CBCT examination; we describe its location and
      morphological characteristics. The variation found was a Type 1 bilateral bifid
      MC, which consists in an accessory canal originating from a single mandibular
      foramen and extending to the third molar or its immediate surroundings. In this
      report we discuss the importance of detecting these anatomical variations, as
      well as their implications in clinical practice.

PMID- 29569707
TI  - Medical students and midwives - How do they view each other?
AB  - Medical students from James Cook University who had completed their rotation in
      obstetrics, and midwives working in Cairns Hospital who had undertaken
      supervision of medical students in the birth suite, were invited to complete
      anonymous questionnaires on their views of their respective roles in the birth
      suite. Several issues were identified including increased medical and midwifery
      student numbers, and lack of communication between midwives and medical students.
      Increased cooperation and communication between medical and midwifery education
      providers is urgently needed to improve both student groups' learning
      experiences.

PMID- 29569708
TI  - A quick glance at noteworthy articles in this month's issue.

PMID- 29569709
TI  - The feasibility of a clinical audit tool to investigate stillbirth in Australia -
      a single centre experience.
AB  - BACKGROUND: The stillbirth rate in Australia is 7 per 1000 births (Australia's
      Mothers and Babies 2014-in brief. Perinatal Statistics Series no. 32. Cat no. PER
      87, Canberra, AIHW, 2016). The Perinatal Society of Australia and New Zealand
      (PSANZ) developed guidelines to standardise the investigations into stillbirth.
      AIMS: To identify causes of stillbirths and stillbirth care using the National
      Perinatal Death Clinical Audit Tool (National Perinatal Death Clinical Audit
      Tool, Australian and New Zealand Stillbirth Alliance [ANZSA]/Perinatal Society of
      Australia and New Zealand [PSANZ]) and compare it to the PSANZ recommendations.
      Documentation of examination findings and follow-up after stillbirth were also
      reviewed. MATERIALS AND METHODS: From the total of 515 registered stillbirths at
      a Queensland hospital, 170 stillbirths were considered unexplained after chart
      review between July 2004 and September 2014. The National Perinatal Death
      Clinical Audit Tool was applied and resulting underlying causes of stillbirths
      were classified using the PSANZ perinatal mortality classification system.
      RESULTS: The stillbirth rate for this centre was 11.2 per 1000 births. A cause of
      fetal death was established in 55.4% (93/168) and 75 cases (44.6%) remained
      unexplained corresponding to 14.6% of all registered stillbirths (75/515). Over
      half of the women (52.7%) were nulliparous. High rates of autopsy (47.3%),
      bereavement support (99.4%) and placental histopathology (98.8%) were noted. The
      general practitioner was notified in 98.7% of cases at the time of stillbirth;
      34.1% of babies were small for gestational age at birth, 18.9% were growth
      restricted at birth and 21.4% of women were current smokers. CONCLUSION: The
      National Perinatal Death Clinical Audit Tool facilitates and streamlines
      stillbirth investigations and thus helps to identify underlying causes of
      stillbirth.

PMID- 29569710
TI  - Wood: Biology of a living tissue.

PMID- 29569712
TI  - Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 2:
      Prediction of Decreased Substrate Exposure After Rifabutin or Carbamazepine.
AB  - Rifampin demonstrated dose-dependent relative induction between cytochrome P
      (CYP)3A and P-glycoprotein (P-gp), organic anion transporting polypeptides
      (OATPs), or CYP2C9; P-gp, OATP, and CYP2C9 induction was one drug-drug
      interaction (DDI) category lower than that observed for CYP3A across a wide range
      of pregnane X receptor (PXR) agonism. The objective of this study was to
      determine if these relationships could be utilized to predict transporter
      induction by other CYP3A inducers (rifabutin and carbamazepine) and of another P
      gp substrate, sofosbuvir. Healthy subjects received sofosbuvir and a six-probe
      drug cassette before and after 300 mg q.d. rifabutin or 300 mg b.i.d.
      carbamazepine. Induction of P-gp, CYP2C9, and decreased sofosbuvir exposure were
      successfully predicted by observed CYP3A induction. Carbamazepine induction of
      OATP was underpredicted, likely due to reported additional non-PXR agonism. The
      results demonstrate that the effect of a PXR agonist on CYP3A can be leveraged to
      inform on induction liability for other primarily PXR-regulated
      P450s/transporters, allowing for prioritization of targeted DDI assessments
      during new drug development.

PMID- 29569711
TI  - Garlic intake and gastric cancer risk: Results from two large prospective US
      cohort studies.
AB  - Although many case-control studies suggested that garlic intake may reduce
      gastric cancer risk, evidence from prospective cohort studies has been lacking.
      We examined the association between garlic intake and subsequent risk of gastric
      cancer among 77,086 women in the Nurses' Health Study (1984-2014) and 46,398 men
      in the Health Professionals Follow-Up Study (1986-2014). Relative risks (RRs) and
      95% confidence intervals (95% CIs) were estimated using Cox proportional hazards
      models. We additionally examined garlic intake in relation to Helicobacter pylori
      (H. pylori) infection among 613 participants using logistic regression. During up
      to 30 years of follow-up, 292 participants were diagnosed with gastric cancer.
      The pooled multivariable RR of gastric cancer among participants who ate garlic,
      as compared to those who did not, were 1.11 (95% CI = 0.81-1.51) for the intake
      of garlic less than once per week, 0.98 (95% CI = 0.71-1.36) for one to four
      times per week and 1.39 (95% CI = 0.89-2.17) for five or more times per week (p
      for trend = 0.23). Similarly, no statistically significant association was
      observed cross-sectionally between garlic intake and H. pylori infection
      (comparing five or more times per week to never, pooled multivariable odds ratio
      = 1.66, 95% CI = 0.89-3.09; p for trend = 0.11). The findings from this large
      prospective study do not support the hypothesis that high garlic intake reduces
      risk of gastric cancer.

PMID- 29569713
TI  - Adiposity and breast cancer risk in postmenopausal women: Results from the UK
      Biobank prospective cohort.
AB  - Body size is an important modifiable risk factor for postmenopausal breast
      cancer. However, it remains unclear whether direct measures of fat mass are
      better indicators of risk than anthropometric measures, or whether central
      adiposity may contribute to risk beyond overall adiposity. We analyzed data from
      162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size
      was measured by trained technicians. Multivariable-adjusted Cox regression was
      used to estimate relative risks. Analyses were stratified by age at recruitment,
      region and socioeconomic status, and adjusted for family history of breast
      cancer, age at menarche, age at first birth, parity, age at menopause, previous
      hormone replacement therapy use, smoking, alcohol intake, height, physical
      activity and ethnicity. We observed 2,913 incident invasive breast cancers during
      a mean 5.7 years of follow-up. There was a continuous increase in risk of
      postmenopausal breast cancer with increasing adiposity, across all measures. The
      point estimate, comparing women in the top (median 37.6 kg) to bottom (median
      17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52-1.90).
      The magnitudes of the associations between per SD increase in BMI and body fat
      mass with breast cancer risk were similar, suggesting impedance measures of fat
      were not substantially better indicators of risk than anthropometric measures.
      After adjusting for body fat mass, the associations between anthropometric
      measures of central adiposity and breast cancer risk were attenuated. The
      magnitude of risk, across all measures of adiposity, was greater in women who had
      been postmenopausal for 12 or more years.

PMID- 29569714
TI  - Unexpected involvement of IL-13 signalling via a STAT6 independent mechanism
      during murine IgG2a development following viral vaccination.
AB  - In this study, recombinant pox viral vaccination was shown to induce highly
      elevated IgG2a and low IgG1 antibody expression in mice lacking IL-4 or STAT6,
      whilst IL-13-/- mice exhibited elevated IgG1, but very low IgG2a. These findings
      revealed that IL-13 and IL-4 differentially regulated antibody development. To
      understand this further, when STAT6-/- mice were given a vaccine co-expressing IL
      13Ralpha2 that temporarily sequestered IL-13, significantly reduced IgG2a
      expression, was detected. These findings for the first time demonstrated that IL
      13 regulated IgG2a differentiation utilising an alternative IL-13R signalling
      pathway independent of STAT6 (IL-13Ralpha2 pathway). This was further
      corroborated by the (i) elevated IL-13Ralpha2 expression detected on STAT6-/-
      lung MHCII+ CD11c+ cells 24 h post IL-13 inhibitor vaccination and ii)
      significant up-regulation of IL-13Ralpha2 expression on spleen and lung derived
      MHCII+ CD11c+ following inhibition of STAT6 signalling in vitro, or vaccination
      with IL-4R/STAT6 antagonist in vivo. When T follicular helper (Tfh) cells which
      regulate antibody differentiation were assessed post vaccination, although no
      difference in IL-4 expression was observed, greatly reduced IFN-gamma expression
      was detected in IL-13-/- and STAT6-/- mice compared to wild-type. These findings
      support the notion that the balance of IL-13 level at the vaccination site can
      differentially regulate T and B-cell immune outcomes.

PMID- 29569715
TI  - A randomized, controlled trial of two strategies of offering the home-based HPV
      self-sampling test to non- participants in the Flemish cervical cancer screening
      program.
AB  - We conducted a randomized, controlled trial to evaluate different strategies of
      offering an HPV-self sampling program, and compared this with two control groups.
      All total of 35,354 women who did not participate in the Flemish cancer screening
      program were included in the study: 9,118 received a HPV self-collection brush
      (RIATOL qPCR HPV genotyping test (qPCR [E6/E7]); 9,098 were offered the
      opportunity to order an HPV-selfsampling brush, 8,830 received the recall letter;
      8,849 received no intervention. Within 12 months after the mailing, 18.7% of the
      women who had received the brush, participated by returning a self-sample sample,
      while 10.6% women allocated to the opt- in group did so. 10.5% women who received
      the standard recall letter, had a PAP smear taken within a period of 12 months;
      while 8% women did so without receiving an intervention at all. Participation in
      postmenopausal women was higher than in women younger than 50 in both self
      sampling arms. Screening by means of the self-sample kit increased by age,
      contradictory when screening is performed by a PAP smear. Of those testing hrHPV
      positive (9.5%), 88.9% attended for follow up cytology. The mean DNA
      concentration, found in the self-sampler, decreased by age, causing a higher
      number of inconclusive results. Our results support the efficacy of a self
      sampling strategy to increase participation in the Flemish screening program.
      Self-sampling seems particularly acceptable to postmenopausal non-responders.
      Future research should focus on the performance of different self-sampling
      devices in post-menopausal women as low DNA concentrations exponentially
      increased over age.

PMID- 29569716
TI  - Genetic and clonal dissection of osteosarcoma progression and lung metastasis.
AB  - Osteosarcoma is a primary malignant bone tumor that has a high potential to
      metastasize to lungs. Little is known about the mechanisms underlying the
      dissemination of OS cancer cells to lungs. We performed whole exome sequencing of
      13 OS primary tumors, with matched lung metastases and normal tissues.
      Phylogenetic analyses revealed that lung metastatic tumors often harbor clones
      that are nonexistent or rare in the matched primary OS tumors. Spatially and
      temporally separated lung metastases were from parallel seeding events with a
      polyphyletic pattern. Loss of TP53 or RB1 is among the early events during OS
      tumorigenesis, while loss of PTEN is involved at the later stages associated with
      lung metastases. Finally, KEAP1 was identified as a novel biomarker for increased
      metastatic risk. Patients whose primary tumors harbored KEAP1 amplification have
      significantly poorer lung-metastasis free survival. This finding was validated in
      two independent datasets. Further, in vitro experiments exhibited that KEAP1
      depletion suppressed the invasion of OS cells. Our findings uncover the patterns
      of clonal evolution during OS progression and highlight KEAP1 as a novel
      candidate associated with the risk of lung metastasis in OS patients.

PMID- 29569718
TI  - Human papillomavirus type specific risk of progression and remission during long
      term follow-up of equivocal and low-grade HPV-positive cervical smears.
AB  - The prevalence of clinically relevant HPV types and their specific risk for
      progression and regression in women with atypical squamous cells of uncertain
      significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) were
      studied in a routine screening population. A 4-year cohort of women (n = 820)
      with ASCUS/LSIL and a positive HPV test in triage were followed for 6-9 years.
      The progression risks for CIN2+/CIN3+ were determined for single (71.2%) and
      multiple HPV infections (28.8%). The CIN2+ progression risk for all HPV 16, all
      HPV 35, single HPV 16 and single HPV 35 infections were 65.3% (95% CI: 59.6
      71.0), 64.4% (95% CI: 50.4-78.4), 63.8% (95% CI: 56.2-71.4) and 73.7% (95% CI:
      53.9-93.5), respectively. Based on CIN2+ progression risks four main groups were
      defined; the HPV 16 group, the HPV 31/33/35 group, the HPV 18/45/51/52 group and
      the HPV 39/56/58/59/66/68 group with progression risks of 65.3% (95% CI: 59.6
      71.0), 62.1% (95% CI: 54.8-69.4), 52.6 (95% CI: 45.9-59.3) and 39.5 (95% CI: 33.0
      46.0), respectively. In multivariate analyses, women in the age group 40-49 years
      had an increased risk of CIN2+ progression. As for CIN3+, HPV 16 had a higher
      progression risk than other HPV risk groups (p < 0.05). In multiple infections
      only HPV 16 had a significant additive CIN3+ progression risk (p < 0.05) as
      compared to other HPV risk groups. In summary, HPV types 16 and 35, including the
      HPV risk group 31/33/35, had a similar CIN2+ progression risk, but only HPV 16
      had a higher risk for CIN3+ progression.

PMID- 29569717
TI  - The effect of FASN inhibition on the growth and metabolism of a cisplatin
      resistant ovarian carcinoma model.
AB  - Overexpression of fatty acid synthase (FASN), a key regulator of the de novo
      synthesis of fatty acids, has been demonstrated in a variety of cancers and is
      associated with poor prognosis and increased multidrug resistance. Inhibition of
      FASN with the anti-obesity drug orlistat has been shown to have significant anti
      tumourigenic effects in many cancers, notably breast and prostate. In our study,
      we investigated whether FASN inhibition using orlistat is an effective adjunctive
      treatment for ovarian cancers that have become platinum resistant using a
      cisplatin-resistant ovarian tumour xenograft model in mice. Mice were treated
      with orlistat or cisplatin or a combination and metabolite analysis and
      histopathology were performed on the tumours ex vivo. Orlistat decreased tumour
      fatty acid metabolism by inhibiting FASN, cisplatin reduced fatty acid beta
      oxidation, and combination treatment delayed tumour growth and induced apoptotic
      and necrotic cell death in cisplatin-resistant ovarian cancer cells over and
      above that with either treatment alone. Combination treatment also decreased
      glutamine metabolism, nucleotide and glutathione biosynthesis and fatty acid beta
      oxidation. Our data suggest that orlistat chemosensitised platinum-resistant
      ovarian cancer to treatment with platinum and resulted in enhanced efficacy.

PMID- 29569719
TI  - A note on Type S/M errors in hypothesis testing.
AB  - Motivated by the recent replication and reproducibility crisis, Gelman and Carlin
      (2014, Perspect. Psychol. Sci., 9, 641) advocated focusing on controlling for
      Type S/M errors, instead of the classic Type I/II errors, when conducting
      hypothesis testing. In this paper, we aim to fill several theoretical gaps in the
      methodology proposed by Gelman and Carlin (2014, Perspect. Psychol. Sci., 9,
      641). In particular, we derive the closed-form expression for the expected Type M
      error, and study the mathematical properties of the probability of Type S error
      as well as the expected Type M error, such as monotonicity. We demonstrate the
      advantages of our results through numerical and empirical examples.

PMID- 29569720
TI  - Drug survival of secukinumab for moderate-to-severe plaque psoriasis.

PMID- 29569721
TI  - Resolvin D1 attenuates liver ischaemia/reperfusion injury through modulating
      thioredoxin 2-mediated mitochondrial quality control.
AB  - BACKGROUND AND PURPOSE: Liver ischaemia and reperfusion (IR) injury is a sterile
      inflammatory response involving production of ROS. Mitochondrial homeostasis is
      maintained by mitochondrial quality control (QC). Thioredoxin (TRX) 2 is a key
      mitochondrial redox-sensitive protein. Resolvin D1 (RvD1), a specialized pro
      resolving lipid mediator, exerts anti-inflammatory and antioxidant activities. We
      investigated mechanisms of RvD1 protection against IR-induced oxidative damage to
      the liver, focusing on TRX2-mediated mitochondrial QC. EXPERIMENTAL APPROACH:
      Mice underwent partial warm IR. RvD1 was administered 1 h before ischaemia and
      immediately prior to reperfusion. Human liver carcinoma HepG2 cells were exposed
      to hypoxia/reoxygenation and transfected with TRX2 siRNA. Immunohistochemistry,
      Western blotting and enzyme assays were used to follow changes in mitochondrial
      structure and function. KEY RESULTS: RvD1 attenuated hepatocellular damage
      following IR, assessed by serum aminotransferase activities and histology. RvD1
      reduced mitochondrial swelling, lipid peroxidation and glutamate dehydrogenase
      release. Impaired activities of mitochondrial complexes I and III were restored
      by RvD1. RvD1 enhanced expression of the mitophagy-related protein, Parkin and
      inhibited accumulation of PTEN-induced putative kinase 1. RvD1 restored levels of
      mitochondrial biogenesis proteins including PPARgamma coactivator 1alpha, nuclear
      respiratory factor 1 and mitochondrial transcription factor A and mtDNA level.
      RvD1 attenuated the increase in levels of the mitochondrial fission-related
      protein, dynamin-related protein 1. IR reduced TRX2 levels while increasing TRX2
      association with TRX-interacting protein. RvD1 attenuated these changes. The
      regulatory effects of RvD1 on mitochondrial QC were abolished by TRX2 knockdown.
      CONCLUSIONS AND IMPLICATIONS: We suggest that RvD1 ameliorated IR-induced
      hepatocellular damage by regulating TRX2-mediated mitochondrial QC.

PMID- 29569723
TI  - Cytochrome P450 3A Induction Predicts P-glycoprotein Induction; Part 1:
      Establishing Induction Relationships Using Ascending Dose Rifampin.
AB  - Drug transporter and cytochrome P450 expression is regulated by shared nuclear
      receptors and, hence, an inducer should induce both, although the magnitude may
      differ. The objective of this study was to establish relative induction
      relationships between CYP3A and drug transporters (P-glycoprotein (P-gp), organic
      anion transporting polypeptide (OATP), and breast cancer resistance protein
      (BCRP)) or other P450s (CYP2C9 and CYP1A2) using ascending doses of the
      prototypical pregnane xenobiotic receptor (PXR) agonist, rifampin, to elicit
      weak, moderate, and strong PXR agonism. Healthy subjects received dabigatran
      etexilate, pravastatin, rosuvastatin, and a midazolam/tolbutamide/caffeine
      cocktail before and after rifampin 2, 10, 75, or 600 mg q.d. Unlike CYP3A, only
      moderate induction of P-gp, OATP, and CYP2C9 was observed and dose-dependent
      induction of P-gp, OATP, and CYP2C9 was always one drug-drug interaction category
      lower than observed for CYP3A, even when correcting for probe drug sensitivity.
      Data from this study establish proof-of-concept that P450 induction data can be
      leveraged to inform on the effect on transporters.

PMID- 29569722
TI  - Etiology of hepatocellular carcinoma in West Africa, a case-control study.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where
      HBV infection is endemic. However, limited information is available on other risk
      factors such as alcohol use, HCV and HIV infection. A case-control study was
      conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and
      Lome (Togo). Cases were matched with controls on age, gender and participating
      site. The diagnosis of HCC relied on the combination of one or more space
      occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and
      an alpha-fetoprotein level >=400 ng/ml. HIV, HBV and HCV serology were performed.
      Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional
      logistic regression model was used to measure odds ratio (OR) with their 95%
      confidence intervals (CI). A total of 160 cases and 320 controls were included.
      Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38-57).
      Hazardous alcohol use (OR = 4.5 [CI 1.1-18.5]), HBV infection (OR = 62.5 [CI 20.5
      190.7]) and HCV infection OR = 35.9 [CI 10.0-130.3]) were independently
      associated with HCC. Combining the effect of HBV infection and alcohol, HBV
      infected hazardous drinkers had an OR = 149.8 (CI 13.5-1 667.0), HBV mono
      infected had an OR = 57.4 (CI 18.8-175.3) (ref: HBV-negative). Aside the
      independent association of alcohol use and HBV and HCV infection with HCC, a
      synergic effect between alcohol use and HBV infection was identified. Timely
      screening and care of HBV infection and hazardous drinking might prevent a
      significant number of HCC in West Africa.

PMID- 29569724
TI  - Multi-regional sequencing reveals intratumor heterogeneity and positive selection
      of somatic mtDNA mutations in hepatocellular carcinoma and colorectal cancer.
AB  - Recent studies have revealed significant intratumor heterogeneity (ITH) of
      nuclear genome mutations and highlighted its function in tumor progression and
      treatment resistance. However, the ITH of somatic mitochondrial DNA (mtDNA)
      mutations detected in cancers remains unknown. In this study, we performed
      multiregional mtDNA sequencing of tumor and paratumor tissue samples from 12
      hepatocellular carcinoma (HCC) and 13 colorectal cancer (CRC) patients. A
      substantial level of mtDNA mutations was found in paired non-HCC inflammatory
      tissues, suggesting that these tissues might not be mtDNA-genetically "normal."
      Moreover, our data indicated that the ITH of somatic mtDNA mutations was a common
      feature in HCC and CRC patients. In addition, we found that shared mutations
      which were observed in at least 2 samples in each patient exhibited a
      significantly higher heteroplasmic level than mutations that were private to a
      specific tumor region from both HCC (p = 0.039) and CRC patients (p = 0.001). The
      heteroplasmic level of shared mutations was positively correlated with
      intratumoral recurrence of mtDNA mutations. We also found that shared mutations
      in tumor tissues with a higher degree of pathogenicity risk exhibited a higher
      heteroplasmic level and intratumoral recurrence in both HCC and CRC patients.
      These findings suggest that some mtDNA mutations may undergo positive selection
      during the clonal expansion. Taken together, our analyses identified various
      levels of ITH of somatic mtDNA mutations in HCC and CRC patients and provided
      evidence supporting the positive selection working on some somatic mtDNA
      mutations in tumor tissues.

PMID- 29569725
TI  - Applicability of and potential barriers preventing allogeneic stem cell
      transplant in sickle cell patients treated outside a sickle cell program.

PMID- 29569726
TI  - Xerostomia, salivary characteristics and gland volumes following intensity
      modulated radiotherapy for nasopharyngeal carcinoma: a two-year follow up.
AB  - BACKGROUND: To evaluate changes in xerostomia status, salivary characteristics
      and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma
      patients. METHODS: Xerostomia scores, salivary flow rates, pH and buffering
      capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months
      and 2 years post-radiotherapy. Salivary gland volumes and their correlation with
      radiation dose were also assessed. RESULTS: Mean radiation dose to oral cavity,
      parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively.
      Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2
      years post-radiotherapy were 84% and 51% of pre-radiotherapy levels,
      respectively. Correlations were observed between parotid gland volume per cent
      reduction and its radiation dose and between resting salivary flow rate reduction
      and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and
      resting saliva pH remained significantly low at 2 years post-radiotherapy (both
      flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia
      scores remained significantly higher compared with pre-radiotherapy levels.
      CONCLUSIONS: Submandibular gland volumetric shrinkage persisted 2 years after
      radiotherapy. Xerostomia scores remained significantly higher, and salivary flow
      rates and resting saliva pH remained significantly lower, suggesting that study
      participants were still at risk for hyposalivation-related oral diseases.

PMID- 29569727
TI  - Iron isomaltoside is superior to iron sucrose in increasing hemoglobin in
      gynecological patients with iron deficiency anemia.

PMID- 29569728
TI  - Automatic intraoperative stitching of nonoverlapping cone-beam CT acquisitions.
AB  - PURPOSE: Cone-beam computed tomography (CBCT) is one of the primary imaging
      modalities in radiation therapy, dentistry, and orthopedic interventions. While
      CBCT provides crucial intraoperative information, it is bounded by a limited
      imaging volume, resulting in reduced effectiveness. This paper introduces an
      approach allowing real-time intraoperative stitching of overlapping and
      nonoverlapping CBCT volumes to enable 3D measurements on large anatomical
      structures. METHODS: A CBCT-capable mobile C-arm is augmented with a red-green
      blue-depth (RGBD) camera. An offline cocalibration of the two imaging modalities
      results in coregistered video, infrared, and x-ray views of the surgical scene.
      Then, automatic stitching of multiple small, nonoverlapping CBCT volumes is
      possible by recovering the relative motion of the C-arm with respect to the
      patient based on the camera observations. We propose three methods to recover the
      relative pose: RGB-based tracking of visual markers that are placed near the
      surgical site, RGBD-based simultaneous localization and mapping (SLAM) of the
      surgical scene which incorporates both color and depth information for pose
      estimation, and surface tracking of the patient using only depth data provided by
      the RGBD sensor. RESULTS: On an animal cadaver, we show stitching errors as low
      as 0.33, 0.91, and 1.72 mm when the visual marker, RGBD SLAM, and surface data
      are used for tracking, respectively. CONCLUSIONS: The proposed method overcomes
      one of the major limitations of CBCT C-arm systems by integrating vision-based
      tracking and expanding the imaging volume without any intraoperative use of
      calibration grids or external tracking systems. We believe this solution to be
      most appropriate for 3D intraoperative verification of several orthopedic
      procedures.

PMID- 29569730
TI  - Determination of phenolic compounds in ancient and modern durum wheat genotypes.
AB  - Due to its significant amount of antioxidants, durum wheat (Triticum turgidum
      ssp. durum) could potentially contribute to the protection against a number of
      chronic diseases, such as diabetes, cardiovascular disease, and cancer. The
      increasing interest toward healthy food among both consumers and scientists has
      moved the focus toward the phytochemical content of whole wheat grains. The aim
      of this study was to identify the phytochemical composition of 22 cultivars
      belonging to old and modern durum wheat genotypes, including antioxidant capacity
      (DPPH and FRAP tests). In addition, five phenolic acids involved in the vanillin
      biosynthesis pathway and in the defence mechanism of plants were screened using
      UHPLC-MS/MS. Remarkable quantitative differences in the amount of the five
      phenolic acids analysed (p < 0.05) were detected among the wheat genotypes
      investigated. Results showed that among the investigated phenolic compounds,
      trans-ferulic acid was the most abundant, ranging from 13.28 to 324.69 MUg/g; all
      the other identified compounds were present at lower concentrations. Moreover,
      significant differences on the antioxidant activity were observed. Collected data
      suggested possible differences between biosynthetic pathway of secondary
      metabolites among durum wheat genotypes.

PMID- 29569729
TI  - A single exercise bout and locomotor learning after stroke: physiological,
      behavioural, and computational outcomes.
AB  - KEY POINTS: Previous work demonstrated an effect of a single high-intensity
      exercise bout coupled with motor practice on the retention of a newly acquired
      skilled arm movement, in both neurologically intact and impaired adults. In the
      present study, using behavioural and computational analyses we demonstrated that
      a single exercise bout, regardless of its intensity and timing, did not increase
      the retention of a novel locomotor task after stroke. Considering both present
      and previous work, we postulate that the benefits of exercise effect may depend
      on the type of motor learning (e.g. skill learning, sensorimotor adaptation)
      and/or task (e.g. arm accuracy-tracking task, walking). ABSTRACT: Acute high
      intensity exercise coupled with motor practice improves the retention of motor
      learning in neurologically intact adults. However, whether exercise could improve
      the retention of locomotor learning after stroke is still unknown. Here, we
      investigated the effect of exercise intensity and timing on the retention of a
      novel locomotor learning task (i.e. split-belt treadmill walking) after stroke.
      Thirty-seven people post stroke participated in two sessions, 24 h apart, and
      were allocated to active control (CON), treadmill walking (TMW), or total body
      exercise on a cycle ergometer (TBE). In session 1, all groups exercised for a
      short bout (~5 min) at low (CON) or high (TMW and TBE) intensity and before (CON
      and TMW) or after (TBE) the locomotor learning task. In both sessions, the
      locomotor learning task was to walk on a split-belt treadmill in a 2:1 speed
      ratio (100% and 50% fast-comfortable walking speed) for 15 min. To test the
      effect of exercise on 24 h retention, we applied behavioural and computational
      analyses. Behavioural data showed that neither high-intensity group showed
      greater 24 h retention compared to CON, and computational data showed that 24 h
      retention was attributable to a slow learning process for sensorimotor
      adaptation. Our findings demonstrated that acute exercise coupled with a
      locomotor adaptation task, regardless of its intensity and timing, does not
      improve retention of the novel locomotor task after stroke. We postulate that
      exercise effects on motor learning may be context specific (e.g. type of motor
      learning and/or task) and interact with the presence of genetic variant (BDNF
      Val66Met).

PMID- 29569731
TI  - Exercise and prostate cancer: From basic science to clinical applications.
AB  - Prostate cancer (PCa) is a disease of increasing medical significance worldwide.
      In developed countries, PCa is the most common non-skin cancer in men, and one of
      the leading causes of cancer-related deaths. Exercise is one of the environmental
      factors that have been shown to influence cancer risk. Moreover, systemic reviews
      and meta-analysis have suggested that total physical activity is related to a
      decrease in the risk of developing PCa. In addition, epidemiological studies have
      shown that exercise, after diagnosis, has benefits regarding PCa development, and
      positive outcome in patients under treatment. The standard treatment for locally
      advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces
      diverse side effects, including loss of libido, changes in body composition
      (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of
      numerous research publications showed that aerobic and/or resistance training
      improve patient's physical condition, such us, cardiorespiratory fitness, muscle
      strength, physical function, body composition, and fatigue. Therefore, exercise
      might counteract several ADT treatment-induced side effects. In addition of the
      aforementioned benefits, epidemiological, and in vitro studies have shown that
      exercise might decrease PCa development. Thus, physical activity might attenuate
      the risk of PCa and supervised exercise intervention might improve deleterious
      effects of cancer treatment, such as ADT side effects. This review article
      provides evidence indicating that exercise could complement, and potentiate, the
      current standard treatments for advanced PCa, probably by creating an unfavorable
      microenvironment that can negatively affect tumor development, and progression.

PMID- 29569732
TI  - Unusual twinning: Additional findings during prenatal diagnosis of twin zygosity
      by single nucleotide polymorphism (SNP) array.
AB  - OBJECTIVE: To evaluate the incidence and characteristics of unusual twinning by
      using single nucleotide polymorphism (SNP) array to identify twin zygosity.
      METHODS: This study reviewed 386 twin pairs who were seen for prenatal or
      postnatal diagnosis and underwent SNP array to detect zygosity. RESULTS: The
      incidence of monozygotic (MZ) twins was 11.36% (25/220) in the assisted
      reproductive technology (ART)-conceived group. Monochorionic dizygotic twins
      represented 3 of 24 monochorionic ART-conceived twin pairs (3/24, 12.50%) but
      none in the spontaneous twin pairs. Among 4 single-embryo transfer twin pairs, 3
      represented unusual twinning, including 2 MZ twin pairs with discordant
      karyotypes and 1 dizygotic twin pair of the same gender. Of the pregnancies with
      2 or more embryos transferred, 7.77% (15/193) were MZ. Additionally, there was a
      dichorionic monozygotic twin pair with placental vascular anastomoses from a day
      5 blastocyst transfer. CONCLUSION: Single nucleotide polymorphism array can
      provide zygosity diagnosis in addition to chromosomal copy number variation and
      uniparental disomy detection. ART twin pregnancies have a risk of unusual
      twinning, such as monochorionic dizygotic, single-embryo transfer twin pairs with
      discordant karyotypes or dizygotic, and dichorionic monozygotic with vascular
      anastomoses from day-5 transfer.

PMID- 29569733
TI  - Sequence variation and detection of a functional promoter polymorphism in the
      lysozyme c-type gene from Ragusano and Grigio Siciliano donkeys.

PMID- 29569734
TI  - Remarkable genetic diversity detected at river buffalo prolactin receptor (PRLR)
      gene and association studies with milk fatty acid composition.
AB  - Prolactin is an anterior pituitary peptide hormone involved in many different
      endocrine activities and is essential for reproductive performance. This action
      is mediated by its receptor, the prolactin receptor, encoded by the PRLR gene. In
      this study, we sequenced and characterized the Mediterranean river buffalo PRLR
      gene (from exon 3 to 10), and we found remarkable genetic diversity. In
      particular, we found 24 intronic polymorphisms and 13 exonic SNPs, seven of which
      were non-synonymous. Furthermore, the polymorphisms identified in the 3'-UTR were
      investigated to establish their possible influence on microRNA binding sites.
      Considering all the amino acid changes and the observed allelic combinations, it
      is possible to deduce at least six different translations of the buffalo
      prolactin receptor and, consequently, the presence at the PRLR gene of at least
      six alleles. Furthermore, we identified a deletion of a CACTACC heptamer between
      nucleotides 1102 and 1103 of exon 10 (3'-UTR), and we developed an allele
      specific PCR to identify the carriers of this genetic marker. Finally, the SNP
      g.11188A>G, detected in exon 10 and responsible for the amino acid replacement
      p.His328Arg, was genotyped in 308 Italian Mediterranean river buffaloes, and an
      association study with milk fat traits was carried out. The statistical analysis
      showed a tendency that approached significance for the AA genotype with higher
      contents of odd branched-chain fatty acids. Thus, our results suggest that the
      PRLR gene is a good candidate for gene association studies with qualitative
      traits related to buffalo milk production.

PMID- 29569735
TI  - Anisakis pegreffii impacts differentiation and function of human dendritic cells.
AB  - Human dendritic cells (DCs) show remarkable phenotypic changes when matured in
      the presence of helminth-derived products. These modifications frequently
      elicited a polarization towards Th2 cells and regulatory T cells thus
      contributing to immunological tolerance against these pathogens. In this study,
      the interaction between DCs and larvae of the zoonotic anisakid nematode Anisakis
      pegreffii was investigated. A. pegreffii larvae were collected from fish hosts,
      and monocyte-derived DCs were cocultured in the presence of the live larvae (L)
      or its crude extracts (CE). In both experimental conditions, A. pegreffii
      impacted DC viability, hampered DC maturation by reducing the expression of
      molecules involved in antigen presentation and migration (ie HLA-DR, CD86, CD83
      and CCR7), increased the phagosomal radical oxygen species (ROS) levels and
      modulated the phosphorylation of ERK1,2 pathway. These biological changes were
      accompanied by the impairment of DCs to activate a T-cell-mediated IFNgamma.
      Interestingly, live larvae appeared to differently modulate DC secretion of
      cytokines and chemokines as compared to CE. These results demonstrate, for the
      first time, the immunomodulatory role of A. pegreffii on DCs biology and
      functions. In addition, they suggest a dynamic contribution of DCs to the
      induction and maintenance of the inflammatory response against A. pegreffii.

PMID- 29569736
TI  - Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in
      hepatitis C genotype 1 patients including those with decompensated cirrhosis who
      failed prior treatment with simeprevir/sofosbuvir.
AB  - BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an
      approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of
      85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also
      approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates
      >=95%. No data are available on the efficacy of retreatment with LDV/SOF in
      patients who failed initial treatment with SIM/SOF. AIM: To evaluate the efficacy
      of retreatment with LDV/SOF +/- ribavirin (RBV) in gen 1 patients who had
      previously failed treatment with SIM/SOF. METHODS: Data from a combined treatment
      cohort of 2 hepatology centres, which included patients previously treated with
      SIM/SOF +/- RBV for 12 weeks but failed to achieve SVR and then underwent
      retreatment with LDV/SOF +/- RBV, were analysed (n = 30). LDV/SOF +/- RBV was
      administered for 12-24 weeks based on the discretion of the treating
      hepatologist. RESULTS: Of the 30 patients, 23 (77%) were male, 77% were Caucasian
      and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had
      decompensated, Child's class B or C cirrhosis. Three patients were liver
      transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved
      SVR. Treatment was well tolerated with 37% reporting no adverse events. The most
      common adverse events were fatigue, headache, insomnia and nausea. Two patients
      with Child's B cirrhosis required hospitalization during treatment for variceal
      haemorrhage and abdominal pain respectively. However, no treatment
      discontinuations or deaths occurred. CONCLUSION: Single tablet fixed-dose
      combination LDV/SOF +/- RBV is efficacious and well tolerated in patients who
      previously failed treatment with SIM/SOF, including those with decompensated
      cirrhosis and recurrent hepatitis C following liver transplantation.

PMID- 29569737
TI  - Comparison of oral health status and daily nutrient intake between elders who
      live alone and elders who live with family: Based on the Korean National Health
      and Nutrition Examination Survey (KNHANES VI) (2013-2015).
AB  - OBJECTIVE: To compare the nutritional factors and oral status of elders living
      alone and elders living with their families in Korea. BACKGROUND: Numerous
      studies have found that the presence of fewer remaining teeth is associated with
      decreased nutrient intake; however, there is no study comparing the nutritional
      status and oral status of elders living alone with that of elders living with
      family based on a nationally representative sample. METHODS: A sample of 2904
      individuals who participated in the sixth Korean National Health and Nutrition
      Examination Survey was reviewed (65-84 years of age). Living status was defined
      according to the participants' self-reported questionnaire, and a nutrient intake
      questionnaire was designed as an open questionnaire and used during the face-to
      face interviews. The number of existing teeth was used to determine oral status.
      A complex-sample general linear analysis and multivariate logistic regression
      analysis were used to evaluate the association between the number of teeth and
      nutrient intake among elders living with family and elders living alone after
      adjusting for confounders. RESULTS: Elders living alone were significantly older
      and tended to have the following characteristics: women, lower household income,
      lower educational level, poor perceived health status, non-smokers, non-drinkers
      and lack of physical activity. Elders living alone had a poorer perceived oral
      health status, had not received an oral examination in the past year, had chewing
      problems and had fewer existing teeth (P < .05). Elders living with family showed
      better oral health and nutrient intake status. Participants who had many existing
      teeth had higher nutrient intake than the participants who had fewer existing
      teeth. CONCLUSIONS: For healthy lives at old age, family support or additional
      social support for elders living alone should be considered.

PMID- 29569738
TI  - Tandem HILIC-RP liquid chromatography for increased polarity coverage in food
      analysis.
AB  - Comprehensive non-targeted analysis of food products normally requires two
      complementary chromatographic runs to achieve maximum compound coverage. In this
      study, we present a sensitive tandem-LC method, which combines RP and HILIC
      separation in a single run. The setup consists of a C18 trap column and two
      subsequently coupled analytical columns (HILIC and C18) which are operated in
      parallel. First, hydrophobic compounds are retained on the RP trap column while
      rather hydrophilic compounds are directly transferred onto a HILIC phase. Next,
      the pre-fractionated sample composition is analyzed by HILIC or RP
      chromatography, respectively. The presented setup allows individual and
      independent gradient elution as well as interfacing with mass spectrometry. The
      performance of the method has been proven by means of food relevant standards and
      analysis of complex food samples (e.g. red wine, meat extract). The simple and
      robust setup provides high flexibility in the selection of column combinations
      and does not require sophisticated instrumental setups or software. The method
      significantly increases the covered polarity range compared to classical one
      dimensional chromatography. Our results indicate that tandem LC is a valuable and
      universal tool in the non-targeted screening of various types of complex food
      samples.

PMID- 29569739
TI  - Chemical exchange-sensitive spin-lock (CESL) MRI of glucose and analogs in brain
      tumors.
AB  - PURPOSE: Glucose uptake and metabolism can be measured by chemical exchange
      sensitive spin-lock (CESL) MRI with an administration of glucose or its analogs.
      This study investigates the sensitivity, the spatiotemporal characteristics, and
      the signal source of glucoCESL with a 9L rat brain tumor model. METHODS: Dynamic
      CESL MRI with intravenous injection of D-glucose, 2-deoxy-D-glucose (2DG), and L
      glucose were measured and compared with gadolinium-based dynamic contrast
      enhanced (DCE) MRI. RESULTS: The CESL signals with an injection of glucose or
      analogs have faster and larger changes in tumors than normal brain tissue. In
      tumors, the CESL signal with 2DG injection has larger and slower peak response
      than that with D-glucose due to the accumulation of 2DG and 2DG-6-phosphate in
      the intracellular compartment, whereas L-glucose, which cannot be transported
      intracellularly by glucose transporters, only induces a small change. The initial
      glucoCESL maps (< 4 minutes) are qualitatively similar to DCE maps, whereas later
      maps (> 4 minutes) show more widespread responses. The rise times of D-glucose
      CESL and 2DG-CESL signals in the tumor are slower than that of DCE. Our data
      suggest that the initial CESL contrast primarily reflects a passive increase of
      glucose content in the extracellular space of tumors due to a higher vascular
      permeability, whereas the later period may have a significant contribution from
      the uptake/metabolism of glucose in the intracellular compartment. CONCLUSIONS:
      Our results demonstrate that glucoCESL MRI has both extracellular and
      intracellular contributions, and can be a useful tool for measurements of both
      vascular permeability and glucose uptake in tumors.

PMID- 29569740
TI  - The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in
      Asians: The Major Drug Causality and Comparison With the US FDA Label.
AB  - Specific ethnic genetic backgrounds are associated with the risk of Stevens
      Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians.
      However, there have been no large cohort, multiple-country epidemiological
      studies of medication risk related to SJS/TEN in Asian populations. Thus, we
      analyzed the registration databases from multiple Asian countries who were
      treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the
      algorithm of drug causality for epidermal necrolysis. Furthermore, those
      medications labeled by the US Food and Drug Administration (FDA) as carrying a
      risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian
      countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium
      ranelate were identified as new potential causes. In addition to sulfa drugs and
      beta-lactam antibiotics, quinolones were also a common cause. Only one
      acetaminophen-induced SJS was identified, while several medications (e.g.,
      oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk
      of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian
      countries investigated in this study.

PMID- 29569741
TI  - The effects of navigator distortion and noise level on interleaved EPI DWI
      reconstruction: a comparison between image- and k-space-based method.
AB  - PURPOSE: To study the effects of 2D navigator distortion and noise level on
      interleaved EPI (iEPI) DWI reconstruction, using either the image- or k-space
      based method. METHODS: The 2D navigator acquisition was adjusted by reducing its
      echo spacing in the readout direction and undersampling in the phase encoding
      direction. A POCS-based reconstruction using image-space sampling function (IRIS)
      algorithm (POCSIRIS) was developed to reduce the impact of navigator distortion.
      POCSIRIS was then compared with the original IRIS algorithm and a SPIRiT-based k
      space algorithm, under different navigator distortion and noise levels. RESULTS:
      Reducing the navigator distortion can improve the reconstruction of iEPI DWI. The
      proposed POCSIRIS and SPIRiT-based algorithms are more tolerable to different
      navigator distortion levels, compared to the original IRIS algorithm. SPIRiT may
      be hindered by low SNR of the navigator. CONCLUSION: Multi-shot iEPI DWI
      reconstruction can be improved by reducing the 2D navigator distortion. Different
      reconstruction methods show variable sensitivity to navigator distortion or noise
      levels. Furthermore, the findings can be valuable in applications such as
      simultaneous multi-slice accelerated iEPI DWI and multi-slab diffusion imaging.

PMID- 29569743
TI  - The psychrotrophic yeast Sporobolomyces roseus LOCK 1119 as a source of a highly
      active aspartic protease for the in vitro production of antioxidant peptides.
AB  - A psychrotrophic yeast strain producing a cold-adapted protease at low
      temperature was classified as Sporobolomyces roseus. In standard YPG medium, S.
      roseus LOCK 1119 synthesized an extracellular protease with an activity of
      approximately 560 U/L. Optimization of medium composition and process temperature
      considerably enhanced enzyme biosynthesis; an approximate 70% increase in
      activity (2060 U/L). The native enzyme was purified to homogeneity by cation
      exchange chromatography followed by a size exclusion step, resulting in a 103
      fold increase in specific activity (660 U/mg) with 25% recovery. The enzyme
      displayed 10%-30% of its maximum activity at 0-25  degrees C, with the optimum
      temperature being 50 degrees C. Protease G8 was strongly inactivated by pepstatin
      A, an aspartic protease inhibitor. The enzyme was used to hydrolyze four natural
      substrates, and their antioxidant activities were evaluated against 1,1-diphenyl
      2-picrylhydrazyl. The highest antioxidant activity (69%) was recorded for beef
      casein.

PMID- 29569744
TI  - Reducing readmission risk following CABG surgery-Doing whatever it takes.

PMID- 29569742
TI  - Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic
      lymphocytic leukemia patients.
AB  - OBJECTIVES: We previously showed that immunization with ex vivo- generated
      autologous dendritic cells loaded with apoptotic tumor cells (Apo-DC) potentiated
      tumor-specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we
      evaluated safety and immunogenicity of Apo-DC in combination with lenalidomide,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose
      cyclophosphamide (CTX). METHODS: Ten previously untreated patients with slowly
      progressing CLL received 5 Apo-DC vaccinations and lenalidomide orally for 24
      weeks either alone (cohort I, n = 5) or together with subcutaneous GM-CSF and
      intravenous CTX (cohort II, n = 5). Tumor-specific T-cell responses were measured
      by proliferation and IFN-gamma ELISPOT assays. Immune monitoring was performed by
      flow cytometry. RESULTS: Dose-limiting toxicity was observed in 3/10 patients, 2
      in cohort I and one in cohort II. One patient developed autoimmune hemolytic
      anemia and another grade 4 thrombocytopenia. Vaccine-induced immune responses
      were seen in 5/5 and 4/5 patients in cohort I and II, respectively. The
      expression of immune checkpoints on T cells did not change significantly.
      CONCLUSIONS: Lenalidomide alone or in combination with GM-CSF and low-dose CTX as
      immune adjuvant to the Apo-DC vaccine elicited tumor-specific T-cell responses in
      CLL patients. However, unexpected toxicity was observed and caution is suggested
      in further exploring this drug as immune adjuvant in CLL.

PMID- 29569745
TI  - Intimal sarcoma of the left atrium.

PMID- 29569746
TI  - Enantioselective resolution of Rac-terbutaline and evaluation of optically pure R
      terbutaline hydrochloride as an efficient anti-asthmatic drug.
AB  - Terbutaline is a beta2 -adrenoceptor agonist for the treatment of asthma and
      chronic obstructive pulmonary disease (COPD). Among the two isomers of
      terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating
      therapeutic effect, while S-isomer has been reported to show side effects. In
      this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral
      resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9%
      enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6
      nebulized solution was prepared in half dosage of Bricanyl(r), which is a
      marketed product of racemic terbutaline and evaluated in vitro aerosol
      performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary
      delivery. From the investigation, it is evident that R-TBH 6 nebulized solution
      of half dosage performed similar fine aerosol characteristics and anti-asthmatic
      effect with Bricanyl(r).

PMID- 29569747
TI  - Acute coronary syndrome with concomittant isolated dissection of the celiac
      trunk.

PMID- 29569748
TI  - Maternal obesity alters uterine NK activity through a functional KIR2DL1/S1
      imbalance.
AB  - In pregnancy, uterine natural killer cells (uNK) play essential roles in
      coordinating uterine angiogenesis, blood vessel remodeling and promoting maternal
      tolerance to fetal tissue. Deviances from a normal uterine microenvironment are
      thought to modify uNK function(s) by limiting their ability to establish a
      healthy pregnancy. While maternal obesity has become a major health concern due
      to associations with adverse effects on fetal and maternal health, our
      understanding into how obesity contributes to poor pregnancy disorders is
      unknown. Given the importance of uNK in pregnancy, this study examines the impact
      of obesity on uNK function in women in early pregnancy. We identify that uNK from
      obese women show a greater propensity for cellular activation, but this
      difference does not translate into increased effector killing potential. Instead,
      uNK from obese women express an altered repertoire of natural killer receptors,
      including an imbalance in inhibitory KIR2DL1 and activating KIR2DS1 receptors
      that favors HLA-C2-directed uNK activation. Notably, we show that obesity-related
      KIR2DS1 skewing potentiates TNFalpha production upon receptor crosslinking.
      Together, these findings suggest that maternal obesity modifies uNK activity by
      altering the response toward HLA-C2 antigen and KIR2DL1/2DS1-controlled TNFalpha
      release. Furthermore, this work identifies alterations in uNK function resulting
      from maternal obesity that may impact early developmental processes important in
      pregnancy health.

PMID- 29569749
TI  - Supravalvular aortic stenosis with a chronic type A aortic dissection.

PMID- 29569750
TI  - Predicting readmission risk shortly after admission for CABG surgery.
AB  - BACKGROUND: Reducing preventable hospital readmissions after coronary artery
      bypass graft (CABG) surgery has become a national priority. Predictive models can
      be used to identify patients at high risk for readmission. However, the majority
      of the existing models are based on data available at discharge. We sought to
      develop a model to predict hospital readmission using data available soon after
      admission for isolated CABG surgery. METHODS: Fifty risk factors were included in
      a bivariate analysis, 16 of which were significantly associated (P < 0.05) with
      readmissions and were entered into a multivariate logistic regression and removed
      stepwise, using backward elimination procedures. The derived model was then
      validated on 896 prospective isolated CABG cases. RESULTS: Of 2589 isolated CABG
      patients identified between December 1, 2010, and June 30, 2014, 237(9.15%) were
      readmitted within 30 days. Five risk factors were predictive of 30-day all-cause
      readmission: age (odds ratio [OR] = 1.03; 95% confidence interval [CI]: 1.01
      1.05; P = 0.004), prior heart failure (OR = 1.55; 95%CI: 1.07-2.24; P = 0.020),
      total albumin prior to surgery (OR = 0.68; 95%CI: 0.05-0.94; P = 0.021), previous
      myocardial infarction (OR = 1.44; 95%CI: 1.00-2.08; P = 0.50), and history of
      diabetes (OR = 1.54; 95%CI: 1.09-2.19; P = 0.015). The area under the curve c
      statistic was 0.63 in the derivation sample and 0.65 in the validation sample
      showing good discrimination. CONCLUSIONS: A 30-day all-cause readmission among
      isolated CABG patients can be predicted soon after admission with a small number
      of risk factors.

PMID- 29569751
TI  - Diagnostic accuracy of dual-source computed tomography angiography for the
      detection of coronary in-stent restenosis: A systematic review and meta-analysis.
AB  - We sought to perform a meta-analysis to comprehensively evaluate the diagnostic
      accuracy of dual-source computed tomography angiography (DSCTA) in detecting
      coronary in-stent restenosis (CISR) when compared to invasive coronary
      angiography. The stent-based research studies in which DSCTA was used as
      diagnostic tool for CISR, as recent as of October 2017, from several reputed
      scientific libraries (PubMed, Embase, Scopus, The Cochrane Library, and Web of
      Science) were evaluated. Study inclusion, data extraction, and risk bias
      assessment were conducted by two researchers independently. Pooled sensitivity
      (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood
      ratio (NLR), diagnostic odds ratio (DOR), and area under summary receiver
      operator characteristics (SROC) curve (AUC) were calculated to assess the
      diagnostic value. In addition, heterogeneity and subgroup analysis were also
      carried out. A total of 13 studies with a total of 894 patients and 1384
      assessable stents were included. The pooled results of DSCTA diagnosing CISR were
      as follows: SEN 0.92 (95% confidence interval [CI] 0.87-0.96), SPE 0.91 (95% CI
      0.87-0.94), PLR 9.83 (95% CI 6.93-13.94), NLR 0.09 (95% CI 0.05-0.15), DOR 114.73
      (95% CI 64.12-205.28), and AUC 0.97 (95% CI 0.95-0.98), respectively. The
      subgroup analysis result suggested that DSTCA performed significantly better in
      CISR detection when the stent diameter was >=3 mm compared with the stent
      diameter <3 mm: (0.98 [0.97-0.99] vs 0.82 [0.79-0.86]) with P < .05. This study
      revealed that DSCTA has excellent diagnostic performance for detecting CISR and
      may serve as an alternative for further patient evaluation with CISR, especially
      for stent diameter >=3 mm.

PMID- 29569752
TI  - Development of mucosal-associated invariant T cells.
AB  - Mucosal-associated invariant T (MAIT) cells develop in the thymus and migrate
      into the periphery to become the largest antigen-specific alphabeta T-cell
      population in the human immune system. However, the frequency of MAIT cells
      varies widely between human individuals, and the basis for this is unclear. While
      MAIT cells are highly conserved through evolution and are phenotypically similar
      between humans and mice, they represent a much smaller proportion of total T
      cells in mice. In this review, we discuss how MAIT cells transition through a
      three-stage development pathway in both mouse and human thymus, and continue to
      mature and expand after they leave the thymus. Moreover, we will explore and
      speculate on how specific factors regulate different stages of this process.

PMID- 29569753
TI  - Comprehensive mapping of cystic fibrosis mutations to CFTR protein identifies
      mutation clusters and molecular docking predicts corrector binding site.
AB  - Cystic Fibrosis (CF) is caused by mutations in the CFTR gene, of which over 2000
      have been reported to date. Mutations have yet to be analyzed in aggregate to
      assess their distribution across the tertiary structure of the CFTR protein, an
      approach that could provide valuable insights into the structure-function
      relationship of CFTR. In addition, the binding site of Class I correctors (VX
      809, VX-661, and C18) is not well understood. In this study, exonic CFTR
      mutations and mutant allele frequencies described in 3 curated databases (ABCMdb,
      CFTR1, and CFTR2, comprising >130 000 data points) were mapped to 2 different
      structural models: a homology model of full-length CFTR protein in the open
      channel state, and a cryo-electron microscopy core-structure of CFTR in the
      closed-channel state. Accordingly, residue positions of 6 high-frequency mutant
      CFTR alleles were found to spatially co-localize in CFTR protein, and a
      significant cluster was identified at the NBD1:ICL4 interdomain interface. In
      addition, immunoblotting confirmed the approximate binding site of Class I
      correctors, demonstrating that these small molecules act via a similar mechanism
      in vitro, and in silico molecular docking generated binding poses for their
      complex with the cryo-electron microscopy structure to suggest the putative
      corrector binding site is a multi-domain pocket near residues F374-L375. These
      results confirm the significance of interdomain interfaces as susceptible to
      disruptive mutation, and identify a putative corrector binding site. The
      structural pharmacogenomics approach of mapping mutation databases to protein
      models shows promise for facilitating drug discovery and personalized medicine
      for monogenetic diseases.

PMID- 29569754
TI  - Evaluation of a bone substitute covered with a collagen membrane for ridge
      preservation after tooth extraction. Clinical and tomographic randomized
      controlled study in humans.
AB  - OBJECTIVE: To evaluate the use of a synthetic bone substitute covered with a
      collagen membrane for ridge preservation after tooth extraction, by clinical and
      tomographic analysis. MATERIAL AND METHODS: Fifteen patients, presenting at least
      two maxillary anterior teeth indicated for extraction, were selected: in the test
      group (TG), post-extraction sockets were filled by a synthetic bone substitute;
      in the control group (CG), by blood clot. In both groups, the sockets were
      covered by a collagen membrane. Cone-beam computerized tomography (CBCT) scans
      were acquired immediately after and 6 months post-surgically, and horizontal and
      vertical dimensional bone changes were quantified. RESULTS: Transurgical clinical
      analysis presented no statistically significant differences between TG and CG (p
      > .05). CBCT intragroup evaluation presented statistically significant reduction
      for the buccal alveolar measurement (TG = 1.58 mm or 21.82%, and CG = 1.66 mm or
      24.08%) and horizontal cervical measurement (TG = 0.55 mm or 8.30% and CG = 1.30
      mm or 17.68%), and not significant for palatal alveolar measurement (TG = 0.44 mm
      or 3.42% and CG = 0.26 mm or 3.89%). For alveolar height and horizontal apical
      measurements, this decrease was significant only for the CG, with reductions of
      1.03 mm and 0.50 mm, respectively, compared to a decrease of 0.57 mm and 0.19 mm
      for the TG. The intergroup analysis showed significant difference for cervical
      horizontal measurement after 6 months (p < .05). CONCLUSION: The results showed
      that the use of the bone substitute covered with a collagen membrane resulted in
      less changes in vertical and horizontal alveolar ridge dimensions than the
      collagen membrane alone.

PMID- 29569755
TI  - LDHA is a direct target of miR-30d-5p and contributes to aggressive progression
      of gallbladder carcinoma.
AB  - Gallbladder cancer (GBC) is the most general biliary tract malignancy, with poor
      prognosis due to rapid tumor progression and lack of specific symptoms. Lactate
      dehydrogenase-A (LDHA) can promote Warburg effect to produce lactate and
      Adenosine Triphosphate (ATP) in aerobic condition, which contributes to
      oncogenesis metastasis and drug resistance in various cancers. However, the
      expression and functional role of LDHA in GBC are largely unknown. We determined
      that LDHA was over-expressed in GBC tumor tissues compared with normal tissues,
      which was also an independent prognostic factor for the overall survival of GBC
      patients by tissue microarrays analysis. In addition, RNAi-mediated LDHA
      silencing could suppress the GBC cell proliferation, invasion, colony formation
      and glycolysis while promoting cell apoptosis in vitro. Similar results were
      observed in GBC cells treated with LDHA specific inhibitor FX11. Moreover, we
      confirmed that knockdown of LDHA could inhibit tumor growth in vivo.
      Additionally, we found that the 3'-untranslated region (3'-UTR) of LDHA mRNA was
      the direct target of microRNA-30d-5p (miR-30d-5p), which was low expressed in GBC
      tissues and associated with poor prognosis of GBC patients. Our findings disclose
      a novel role for miR-30d-5p/LDHA axis contribute to aggressive progression by
      reprogramming the metabolic process in GBC cells, and suggest a potential
      application of miR-30d-5p/LDHA axis in prognosis prediction and GBC treatment.

PMID- 29569756
TI  - Kinetic models for the effect of temperature on flavonoid production in liquid
      submerged fermentation by Phellinus baumii.
AB  - Kinetic models and temperature control strategy were established to reflect the
      effect of temperature (22  degrees C-30  degrees C) on flavonoid production of
      Phellinus baumii (P. baumii) in 6-L fermentor. A modified Logistic equation,
      Hinshelwood model, and Luedeking Piret equation were used to describe mycelial
      growth and product formation. The influence of temperature on the estimated
      kinetic parameters was further studied by regression analysis. Based on kinetic
      parameters analysis, the new temperature control strategy was proposed. Briefly,
      at 0-43 H, decreasing temperature (30  degrees C-28  degrees C) can shorten the
      lag phase of mycelial growth, and at 43-90 H, fermentation temperature was
      reduced gradually from 28  degrees C to 24  degrees C to keep high flavonoid
      productivity. At the fermentation anaphase (90-161 H), temperature was controlled
      at 24  degrees C to relieve inhibition of flavonoid and maintain constant
      production capacity of flavonoid. As a result, the maximum flavonoid yield was
      reached 4.21 mg/100 mg cell dry weight by temperature control strategy, which was
      70.45% higher than that at a constant temperature of 26  degrees C. Additionally,
      the establishment of kinetic models based on fermentation temperature, which
      presented here may provide a scientific basis for further large scales flavonoid
      production of P. baumii in submerged fermentation.

PMID- 29569757
TI  - Quinine-modified polymer monolithic column with reversed-phase /strong anion
      exchange mixed-mode for pressurized capillary electrochromatography.
AB  - Via the facile ring-opening reaction of epoxy groups with quinine, a novel
      polymer monolith with quaternary ammonium for reversed-phase/strong anion
      exchange mixed-mode has been fabricated for pressurized capillary
      electrochromatography (pCEC). Optimization on the preparation of quinine-modified
      monoliths has been investigated, and characteristics including morphology,
      permeability, mechanical stability, reproducibility, and column performance have
      been also studied. Active quaternary ammonium groups were conveniently produced
      to generate cationic action sites and stable anodic electroosmotic flow. Multiple
      interactions including reversed-phase, strong anion-exchange, electrostatic
      repulsion and pi-pi stacking interactions were obtained. Satisfactory separation
      capability of various analytes such as alkylbenzenes, polycyclic aromatic
      hydrocarbons, benzoic acid and its homologs, and beta2 -receptor excitants has
      been achieved. Applied to the real sample, the good resolution of three alkaloids
      in Corydalis yanhusuo were achieved by pCEC with the quinine-modified monolith.
      The results light a potential access to facilely fabricating quaternary ammonium
      functionalized polymer monolith with multiple interactions for efficient
      electrochromatography profiling of various compounds.

PMID- 29569758
TI  - XPC gene mutations in families with xeroderma pigmentosum from Pakistan;
      prevalent founder effect.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder
      characterized by hyperpigmentation, premature skin aging, ocular and cutaneous
      photosensitivity, and increased risk of skin carcinoma. We investigated seven
      consanguineous XP families with nine patients from Pakistan. All the Patients
      exhibited typical clinical symptoms of XP since first year of life. Whole genome
      SNP genotyping identified a 14 Mb autozygous region segregating with the disease
      phenotype on chromosome 3p25.1. DNA sequencing of XPC gene revealed a founder
      homozygous splice site mutation (c.2251-1G>C) in patients from six families (A-F)
      and a homozygous nonsense mutation (c.1399C>T; p.Gln467*) in patients of family
      G. This is the first report of XPC mutations, underlying XP phenotype, in
      Pakistani population.

PMID- 29569759
TI  - A breathtaking DRESS due to amoxicillin-clavulanate presenting as polymorphic
      eruption of the pregnancy.

PMID- 29569760
TI  - Changing prevalence of diabetes mellitus in bullous pemphigoid: it is the
      dipeptidyl peptidase-4 inhibitors.

PMID- 29569761
TI  - The "ripple effect": Health and community perceptions of the Indigenous Marathon
      Program on Thursday Island in the Torres Strait, Australia.
AB  - ISSUE ADDRESSED: Physical inactivity is a key health risk among Aboriginal and
      Torres Strait Islander (Indigenous) Australians. We examined perceptions of the
      Indigenous Marathon Program (IMP) in a remote Torres Strait island community.
      METHODS: Semi-structured interviews with community and program stakeholders (n =
      18; 14 Indigenous) examined barriers and enablers to running and the influence of
      the IMP on the community. A questionnaire asked 104 running event participants (n
      = 42 Indigenous) about their physical activity behaviours, running motivation and
      perceptions of program impact. Qualitative data were analysed using thematic
      content analysis, and quantitative data were analysed using descriptive
      statistics. RESULTS: Interviews revealed six main themes: community readiness,
      changing social norms to adopt healthy lifestyles, importance of social support,
      program appeal to hard-to-reach population groups, program sustainability and
      initiation of broader healthy lifestyle ripple effects beyond running. Barriers
      to running in the community were personal (cultural attitudes; shyness) and
      environmental (infrastructure; weather; dogs). Enablers reflected potential
      strategies to overcome described barriers. Indigenous questionnaire respondents
      were more likely to report being inspired to run by IMP runners than non
      Indigenous respondents. CONCLUSIONS: Positive "ripple" effects of the IMP on
      running and broader health were described to have occurred through local role
      modelling of healthy lifestyles by IMP runners that reduced levels of "shame" and
      embarrassment, a common barrier to physical activity among Indigenous
      Australians. A high initial level of community readiness for behaviour change was
      also reported. SO WHAT?: Strategies to overcome this "shame" factor and community
      readiness measurement should be incorporated into the design of future Indigenous
      physical activity programs.

PMID- 29569762
TI  - NDRG1 and FOXO1 regulate endothelial cell proliferation in infantile haemangioma.
AB  - The etiopathogenesis of infantile haemangioma has not been well understood, and
      it is accepted that angiogenic mediator dysregulation is the main contributor to
      the abnormal haemangioma capillary formation. The role of NDRG1, a hypoxia
      inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR
      complex 2 pathway in infantile haemangioma have not been studied yet. The purpose
      of this study was to investigate NDRG1 and FOXO1 expression in the infantile
      haemangioma and the correlation of these proteins with proliferation and
      involution. Primary endothelial cells were obtained, with parental agreement,
      from 12 infantile haemangioma patients during surgery; 6 patients had
      proliferating infantile haemangiomas and 6 had involuting IHs. We compared the
      infantile haemangioma tissues and primary endothelial cells with human vein
      endothelial cells using microarrays, real-time PCR, Western blotting and
      immunohistochemical staining. Our data indicated that FOXO1 expression was
      downregulated in proliferating infantile haemangioma tissue. We found that the
      expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during
      haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell
      proliferation and downregulated c-MYC oncoprotein levels. Our findings suggest
      that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation
      plays an important role in infantile haemangiomas pathogenesis.

PMID- 29569763
TI  - New bone formation after transcrestal sinus floor elevation was influenced by
      sinus cavity dimensions: A prospective histologic and histomorphometric study.
AB  - OBJECTIVE: The aim of this multicenter prospective study was to analyze
      clinically and histologically the influence of sinus cavity dimensions on new
      bone formation after transcrestal sinus floor elevation (tSFE). MATERIAL AND
      METHODS: Patients needing maxillary sinus augmentation (residual crest height <5
      mm) were treated with tSFE using xenogeneic granules. Six months later, bone-core
      biopsies were retrieved for histological analysis in implant insertion sites.
      Bucco-palatal sinus width (SW) and contact between graft and bone walls (WGC)
      were evaluated on cone beam computed tomography, and correlations between
      histomorphometric and anatomical parameters were quantified by means of forward
      multiple linear regression analysis. RESULTS: Fifty consecutive patients were
      enrolled and underwent tSFE procedures, and forty-four were included in the final
      analysis. Mean percentage of newly formed bone (NFB) at 6 months was 21.2 +/-
      16.9%. Multivariate analysis showed a strong negative correlation between SW and
      NFB (R2  = .793) and a strong positive correlation between WGC and NFB (R2  =
      .781). Furthermore, when SW was stratified into three groups (<12 mm, 12 to 15
      mm, and >15 mm), NFB percentages (36%, 13% and 3%, respectively) resulted
      significantly different. CONCLUSIONS: This study represented the first
      confirmation based on histomorphometric data that NFB after tSFE was strongly
      influenced by sinus width and occurred consistently only in narrow sinus cavities
      (SW <12 mm, measured between buccal and palatal walls at 10-mm level, comprising
      the residual alveolar crest).

PMID- 29569764
TI  - Abstracts of Papers Presented at the Health Services Research and Pharmacy
      Practice Conference, 12-13 April 2018, University of Newcastle, UK.

PMID- 29569765
TI  - Induction of IL-10-balanced immune profiles following exposure to LTA from
      Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis colonises human skin without apparent inflammation,
      but a dominance of S. epidermidis and S. aureus is characteristic of cutaneous
      microbial dysbiosis in atopic dermatitis (AD). While S. aureus can trigger AD,
      the role of S. epidermidis is less understood. We characterised consequences of
      innate immune sensing of lipoteichoic acid (LTA) preparations derived from S.
      epidermidis (epi-LTA) or S. aureus (aureus-LTA). Therefore, dendritic cell (DC)
      activation and consecutive priming of antigen-specific T cells following exposure
      of DC to epi-LTA or aureus-LTA were investigated. Mimicking acute AD, exposure of
      DC to IL-4 and LTAs was analysed. Exposure to epi-LTA or aureus-LTA activated
      human immune cells and murine dendritic cells (DCs) via TLR2/MyD88, however,
      resulting in divergent immune profiles. Differences between LTAs were significant
      for IL-6, IL-12p40 and IL-12p70 but not for IL-10, which was best reflected by
      the IL-12p70-to-IL-10 ratio being IL-10-balanced for epi-LTA but pro-inflammatory
      for aureus-LTA. LTA-exposed DCs activated CD4+ T cells; however, while T-cell
      derived IL-10 was equivalent between LTAs, IFN-gamma and IL-17 were significantly
      higher for aureus-LTA. Mimicking acute AD by exposing DCs to IL-4 and LTAs
      revealed that IL-4 significantly and uniformly suppressed epi-LTA-induced
      cytokine production, keeping the IL-12p70-to-IL-10 ratio balanced. In contrast,
      exposure of DCs to aureus-LTA and IL-4 enhanced IL-12p70 but suppressed IL-10
      levels, further unbalancing the IL-12p70-to-IL-10 ratio. These data demonstrate
      opposing immune consequences following exposure to staphylococcal LTAs. Epi-LTA
      induced IL-10-balanced, aureus-LTA pro-inflammatory immune profiles.

PMID- 29569766
TI  - Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell
      renal cell carcinoma progression.
AB  - OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is characterized
      histologically by accumulation of cholesterol esters, cholesterol and other
      neutral lipids. Lysosomal acid lipase (LAL) is a critical enzyme involved in the
      cholesterol ester metabolism. Here, we sought to determine whether LAL could
      orchestrate metabolism of cholesterol esters in order to promote ccRCC
      progression. MATERIALS AND METHODS: Quantitative reverse-transcription PCR and
      western blots were conducted to assess the expression of LAL in human ccRCC
      tissues. We analysed the relationship between LAL levels and patient survival
      using tissue microarrays. We used cell proliferation assays, colony formation
      assays, cell death assays, metabolic assays and xenograft tumour models to
      evaluate the biological function and underlying mechanisms. RESULTS: LAL was up
      regulated in ccRCC tissue. Tissue microarray analysis revealed higher levels of
      LAL in advanced grades of ccRCC, and high LAL expression indicated lower patient
      survival. Suppressing LAL expression not only blocked the utilization of
      cholesterol esters but also impaired proliferation and cellular survival.
      Furthermore, immunohistochemistry staining showed that LAL expression was
      correlated with Akt phosphorylation. Suppressing LAL expression decreased the
      phosphorylation level of Akt and Src and reduced the level of 14,15
      epoxyeicosatrienoic acids in ccRCC cells. Supplement of 14,15-epoxyeicosatrienoic
      acids rescued proliferation in vitro and in vivo. CONCLUSIONS: LAL promoted cell
      proliferation and survival via metabolism of epoxyeicosatrienoic acids and
      activation of the Src/Akt pathway.

PMID- 29569767
TI  - Marginal bone loss at implants with different surface characteristics - A 20-year
      follow-up of a randomized controlled clinical trial.
AB  - OBJECTIVE: This report is a 20-year follow-up of a randomized controlled clinical
      trial evaluating the potential long-term effect of a modified implant surface on
      the preservation of the peri-implant marginal bone level. MATERIAL & METHODS: In
      each of 51 patients and for each fixed partial denture (FPD), by randomization at
      least one implant installed had a non-modified turned surface and one a modified
      and roughened surface (TiOblast(r) ). Clinical and radiological examinations were
      performed at various follow-up intervals. Primary outcome variables were peri
      implant marginal bone level change from time of loading and proportion of
      implants with no bone loss at 20 years. Multilevel analysis followed by
      nonparametric and Pearson's Chi-Square tests were applied for statistical
      analysis. RESULTS: At the 20-year follow-up, 25 patients carrying 64 implants
      were available for evaluation. Turned and TiOblast implants presented with a mean
      bone level change from the time of FDP delivery amounting to -0.41 mm (95% CI 
      0.84/0.02) and -0.83 mm (95% CI -1.38/-0.28) respectively (inter-group comparison
      p > .05). 47% of the Turned and 34% TiOblast implants (p > .05) showed no bone
      loss. All but one of these implants were free of bacterial plaque and
      inflammation as well as presented with probing pocket depths <=5 mm at both the 5
      and 20-year follow-up examinations. CONCLUSION: It is suggested that a moderate
      increase of implant surface roughness has no beneficial effect on long-term
      preservation of the peri-implant marginal bone level.

PMID- 29569768
TI  - Developing a culturally appropriate branding for a social and emotional wellbeing
      intervention in an Aboriginal community.
AB  - ISSUE ADDRESSED: An initial consultation process to implement a culturally
      appropriate social and emotional wellbeing campaign in an Aboriginal community
      indicated that the fundamental principles of the Act-Belong-Commit mental health
      promotion campaign were acceptable, but that a cultural adaptation of the
      branding should be sought. METHODS: A competition was held inviting community
      members to design a brand logo for the campaign in their community. Local judges
      selected "winners" in various categories, and six of the submissions were
      selected for testing in the broader community via street intercept interviews.
      Respondents were asked which logo they liked best, their perceived meanings of
      the designs and the perceived appropriateness of the designs for a social and
      emotional wellbeing campaign. RESULTS: A convenience sample of N = 26 local
      Aboriginal people who lived and/or worked in Roebourne completed the
      questionnaire. There was a clear majority preference for logo "D," which
      communicated appropriate meanings of pride and strength in standing together, and
      reflected the underlying strengths and capacities of Aboriginal people which this
      project seeks to harness and support. CONCLUSIONS: The approach of using a logo
      competition to develop the campaign brand was highly successful and enabled
      further meaningful engagement with the community and other service providers in
      the town. The success of the competition process resulted from an emphasis on
      relationship building, listening to the local community and involving the
      community in decision-making. So what? By conforming to established, but not
      always adhered to, recommendations for community consultation, successful and
      more enduring outcomes are likely.

PMID- 29569769
TI  - Intra- and interobserver variability of image-based PASI assessments in 120
      patients suffering from plaque-type psoriasis.
AB  - BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the standard for
      psoriasis severity assessment. However, PASI measurement is complex and
      subjective, frequently leading to a high intra- and interobserver variability. To
      date, the precise extent of variability in PASI measurements and its underlying
      causes remain unknown. OBJECTIVE: To determine the inter- and intrarater
      variability of image-based PASI measurements by calculating Intra-Class
      Correlation-Coefficients (ICCs) and to investigate the impact of the different
      PASI components and specific anatomic regions on the extent of variability.
      METHODS: First, the methodology of 'image-based' vs. commonly used 'live' PASI
      measurements was validated in a pilot study. Next, in an observational cohort
      study, PASI scores of 120 patients affected by plaque psoriasis were
      prospectively evaluated by three formally trained physicians by means of total
      body images (TBI). Each observer independently performed two rounds of image
      based PASI calculations in all patients at two different time points. RESULTS:
      Overall, 720 image-based PASI scores were calculated with a mean PASI of 8.8
      (range 0.7-34.8). An interrater variability with an ICC of 0.895 and mean
      absolute difference (MAD) of 3.3 PASI points were observed. Intrarater
      variability showed a mean ICC of 0.877 and a MAD of 2.2 points. When considering
      specific PASI components, the highest agreement was found for the assessment of
      the involved body surface area (BSA), while the lowest ICCs were calculated for
      severity scoring of 'scaling' and 'induration'. As BSA scores serve as a
      multiplier in the calculation of PASI, minor inaccuracies were capable of
      inducing a large share of variability. CONCLUSION: The overall inter- and
      intrarater reliability of image-based PASI measurements in this study was good.
      However, physicians were formally trained and experienced, which frequently is
      not the case in a real-life clinical setting. Therefore, new strategies for
      higher standardization and objectivity of PASI calculations are needed.

PMID- 29569770
TI  - Immediate effects and outcome of in-utero pulmonary valvuloplasty in fetuses with
      pulmonary atresia with intact ventricular septum or critical pulmonary stenosis.
AB  - OBJECTIVE: To assess the immediate effects of fetal pulmonary valvuloplasty on
      right ventricular (RV) size and function as well as in-utero RV growth and
      postnatal outcome. METHODS: Patients with pulmonary atresia with intact
      ventricular septum (PAIVS) or critical pulmonary stenosis (CPS) who underwent
      fetal pulmonary valvuloplasty at our center between October 2000 and July 2017
      were included. Echocardiographic data obtained before and after the procedure
      were analyzed retrospectively (median interval after intervention, 1 (range, 1-3)
      days) for ventricular and valvular dimensions and ratios, RV filling time
      (duration of tricuspid valve (TV) inflow/cardiac cycle length), TV velocity time
      integral (TV-VTI) * heart rate (HR) and tricuspid regurgitation (TR) velocity.
      Longitudinal data were collected from only those fetuses followed up in our
      center. Outcome was assessed using the scoring system as described by Roman et
      al. for non-biventricular outcome. RESULTS: Thirty-five pulmonary valvuloplasties
      were performed in our institution on 23 fetuses with PAIVS (n = 15) or CPS (n =
      8). Median gestational age at intervention was 28 + 4 (range, 23 + 6 to 32 + 1)
      weeks. No fetal death occurred. Immediately after successful intervention,
      RV/left ventricular length (RV/LV) ratio (P <= 0.0001), TV/mitral valve annular
      diameter (TV/MV) ratio (P <= 0.001), RV filling time (P <= 0.00001) and TV-VTI *
      HR (P <= 0.001) increased significantly and TR velocity (P <= 0.001) decreased
      significantly. In fetuses followed longitudinally to delivery (n = 5), RV/LV and
      TV/MV ratios improved further or remained constant until birth. Fetuses with
      unsuccessful intervention (n = 2) became univentricular, all others had either a
      biventricular (n = 15), one-and-a-half ventricular (n = 3) or still undetermined
      (n = 3) outcome. Five of nine fetuses with a predicted non-biventricular outcome,
      in which the procedure was successful, became biventricular, while two of nine
      had an undetermined circulation. CONCLUSION: In selected fetuses with PAIVS or
      CPS, in-utero pulmonary valvuloplasty led immediately to larger RV caused by
      reduced afterload and increased filling, thus improving the likelihood of
      biventricular outcome even in fetuses with a predicted non-biventricular
      circulation. (c) 2018 The Authors. Ultrasound in Obstetrics & Gynecology
      published by John Wiley & Sons Ltd on behalf of the International Society of
      Ultrasound in Obstetrics and Gynecology.

PMID- 29569771
TI  - Identification of the acid-induced degradation products of omeprazole and 5
      hydroxyomeprazole by high-resolution mass spectrometry.
AB  - RATIONALE: Omeprazole is used to treat gastric disorders and is one of the most
      commonly consumed drugs in the western world. It forms several metabolites but is
      mostly excreted unchanged and as 5-hydroxyomeprazole. Since omeprazole is widely
      prescribed, its excretion from the body has a potential environmental effect.
      After excretion it will enter the wastewater system and if not adequately removed
      during wastewater treatment will be discharged into rivers in the wastewater
      effluent. It is important to consider not only the parent drug, but also the main
      metabolite (5-hydroxyomeprazole) and their degradation products to fully
      understand the fate of this drug during wastewater treatment. In order to do this
      potential degradation products need to be determined. METHODS: Acid was used to
      artificially accelerate the degradation of omeprazole and 5-hydroxyomeprazole. A
      Q-Exactive Orbitrap mass spectrometer with an electrospray ionisation source was
      used to determine precursor and product ion data for the degradation products.
      RESULTS: Both starting materials quickly degrade under acidic conditions and the
      main degradation product formed in each case was a re-arranged monomer. Other
      species identified were doubly and singly charged dimers with varying numbers of
      sulphur atoms in the dimer bridge. Careful inspection of the accurate mass,
      isotope pattern, isotope abundance and product ion spectra was used to interpret
      the data. CONCLUSIONS: The resultant degradants from omeprazole and 5
      hydroxyomeprazole were analogous to each other, differing only by an oxygen atom.
      This investigation determined the degradation products of omeprazole and 5
      hydroxyomeprazole and proposed structures based on the accurate mass and isotope
      information. The product ions from the degradation products are also reported.

PMID- 29569772
TI  - Topical propranolol for infantile haemangiomas: a systematic review.
AB  - Infantile haemangiomas are the most common tumour of infancy. Whilst the majority
      are left untreated to involute spontaneously, residual skin changes commonly
      occur, particularly in superficial haemangiomas. The current first-line treatment
      for problematic lesions is oral propranolol; however due to the risk of systemic
      adverse effects, the use of off-label topical preparations has recently been
      investigated. Our systematic review was conducted in accordance with PRISMA
      guidelines. Four databases were searched to identify original articles evaluating
      the use of topical propranolol as the primary therapy for infantile haemangiomas.
      Twelve articles with a total of 597 patients and 632 haemangiomas were included.
      Three topical propranolol preparations were used, creams, ointments and gels and
      were all prepared by local pharmaceutical laboratories. The concentration of
      propranolol ranged from 0.5% to 5%. Treatment duration ranged from two weeks to
      16.5 months. Overall, 90% of lesions improved following the initiation of topical
      propranolol. A good or excellent response, defined as a reduction in the size of
      at least 50%, was seen in 59% of lesions. Earlier initiation of treatment (less
      than 3 months of age) was associated with improved outcomes. No systemic adverse
      effects were reported. Minor local reactions were seen in 1.3% of patients.
      Topical propranolol is safer than oral propranolol, though may be less effective.
      Topical propranolol may be more suitable for patients with small, superficial
      haemangiomas at risk of cosmetic sequelae, where the cosmetic or symptomatic
      impact does not warrant oral propranolol treatment.

PMID- 29569774
TI  - Editorial Comment to Prediction models for progression of non-muscle-invasive
      bladder cancer: A review.

PMID- 29569775
TI  - Editorial Comment to Prognostic factors of prostate cancer mortality in a Finnish
      randomized screening trial.

PMID- 29569776
TI  - Editorial Comment to Transsphincteric repair of rectourethral fistulas: 15 years
      of experience with the York Mason approach.

PMID- 29569778
TI  - In situ organic compound analysis on a meteorite surface by desorption
      electrospray ionization coupled with an Orbitrap mass spectrometer.
AB  - RATIONALE: Since extraterrestrial organic matter in meteorites is a very complex
      mixture that is hard to ionize due to its association with minerals, in situ
      analysis of polar organic compounds has never been performed. In addition, when
      studying powdered samples, spatial information of organic compounds is lost.
      METHODS: In situ molecular analysis and chemical imaging of polar organic
      compounds were performed on a meteorite surface by desorption electrospray
      ionization coupled with high-resolution mass spectrometry (DESI-HRMS) using an
      Orbitrap mass spectrometer. RESULTS: Many CHN compounds, including alkylated
      pyridine and imidazole homologues, were identified from the complex peaks by HRMS
      using a spray of electrically charged methanol with a spatial resolution of
      approximately 50 MUm. The same alkylated homologues have the same spatial
      distribution in the meteorite matrix, while alkylpyridines occur in a different
      location from alkylimidazoles. CONCLUSIONS: The compound distribution suggests a
      different source for each compound series or a chromatographic separation effect
      associated with fluid movement in the meteorite parent body. The DESI-HRMS
      imaging will further our understanding of organic compound distribution with
      respect to mineral and water interactions in meteorites.

PMID- 29569777
TI  - Maternal components of RNA-directed DNA methylation are required for seed
      development in Brassica rapa.
AB  - Small RNAs trigger repressive DNA methylation at thousands of transposable
      elements in a process called RNA-directed DNA methylation (RdDM). The molecular
      mechanism of RdDM is well characterized in Arabidopsis, yet the biological
      function remains unclear, as loss of RdDM in Arabidopsis causes no overt defects,
      even after generations of inbreeding. It is known that 24 nucleotide Pol IV
      dependent siRNAs, the hallmark of RdDM, are abundant in flowers and developing
      seeds, indicating that RdDM might be important during reproduction. Here we show
      that, unlike Arabidopsis, mutations in the Pol IV-dependent small RNA pathway
      cause severe and specific reproductive defects in Brassica rapa. High rates of
      abortion occur when seeds have RdDM mutant mothers, but not when they have mutant
      fathers. Although abortion occurs after fertilization, RdDM function is required
      in maternal somatic tissue, not in the female gametophyte or the developing
      zygote, suggesting that siRNAs from the maternal soma might function in filial
      tissues. We propose that recently outbreeding species such as B. rapa are key to
      understanding the role of RdDM during plant reproduction.

PMID- 29569779
TI  - Cytosolic invertases contribute to cellulose biosynthesis and influence carbon
      partitioning in seedlings of Arabidopsis thaliana.
AB  - In plants, UDP-glucose is the direct precursor for cellulose biosynthesis, and
      can be converted into other NDP-sugars required for the biosynthesis of wall
      matrix polysaccharides. UDP-glucose is generated from sucrose by two distinct
      metabolic pathways. The first pathway is the direct conversion of sucrose to UDP
      glucose and fructose by sucrose synthase. The second pathway involves sucrose
      hydrolysis by cytosolic invertase (CINV), conversion of glucose to glucose-6
      phosphate and glucose-1-phosphate, and UDP-glucose generation by UDP-glucose
      pyrophosphorylase (UGP). Previously, Barratt et al. (Proc. Natl Acad. Sci. USA,
      106, 2009 and 13124) have found that an Arabidopsis double mutant lacking CINV1
      and CINV2 displayed drastically reduced growth. Whether this reduced growth is
      due to deficient cell wall production caused by limited UDP-glucose supply,
      pleiotropic effects, or both, remained unresolved. Here, we present results
      indicating that the CINV/UGP pathway contributes to anisotropic growth and
      cellulose biosynthesis in Arabidopsis. Biochemical and imaging data demonstrate
      that cinv1 cinv2 seedlings are deficient in UDP-glucose production, exhibit
      abnormal cellulose biosynthesis and microtubule properties, and have altered
      cellulose organization without substantial changes to matrix polysaccharide
      composition, suggesting that the CINV/UGP pathway is a key metabolic route to UDP
      glucose synthesis in Arabidopsis. Furthermore, differential responses of cinv1
      cinv2 seedlings to exogenous sugar supplementation support a function of CINVs in
      influencing carbon partitioning in Arabidopsis. From these data and those of
      previous studies, we conclude that CINVs serve central roles in cellulose
      biosynthesis and carbon allocation in Arabidopsis.

PMID- 29569780
TI  - A new nonsense mutation in the POGLUT1 gene in two sisters with Dowling-Degos
      disease.

PMID- 29569781
TI  - Are dermatologists who treat patients with delusional infestation at risk of
      major complaints and being stalked?

PMID- 29569782
TI  - An investigation of the cost of food in the Geelong region of rural Victoria:
      Essential data to support planning to improve access to nutritious food.
AB  - ISSUE ADDRESSED: Affordability of a healthy diet is a determinant of nutritional
      intake and therefore health. This project aimed to measure the cost of healthy
      foods across a geographically defined region and examine factors related to
      changing food prices to assist in informing health promotion practice. METHODS:
      The cost of a healthy food basket was measured using the Victorian Healthy Food
      Basket tool, in all eligible stores, across five rural local government areas in
      Western Victoria, Australia in 2014, 2015 and 2016. One-way analysis of variance
      was used to investigate differences in healthy food basket cost across years.
      Multivariable linear regression models were constructed to adjust for baseline
      (2014) cost to determine factors associated with cost. RESULTS: Data were
      collected from 45 stores in 2014 and 2015 and 48 stores in 2016. The average cost
      of the healthy food basket was $459 in 2014, $437 in 2015 and $443 in 2016. The
      cost of the healthy food basket was the highest in stores >15 km from the major
      regional centre and in areas with only one supermarket (non-cluster) (P < .05).
      All food groups except fruit and vegetables decreased in price between 2014 and
      2016. CONCLUSIONS: This project highlights distance from regional centres and
      competition as possible factors that influence the cost of healthy food. SO
      WHAT?: This is valuable insight for health promoters in designing both local
      level interventions aimed at improving access to healthy food and influencing
      regional food systems.

PMID- 29569783
TI  - JRE4 is a master transcriptional regulator of defense-related steroidal
      glycoalkaloids in tomato.
AB  - Steroidal glycoalkaloids (SGAs) are specialized anti-nutritional metabolites that
      accumulate in Solanum lycopersicum (tomato) and Solanum tuberosum (potato). A
      series of SGA biosynthetic genes is known to be upregulated in Solanaceae species
      by jasmonate-responsive Ethylene Response Factor transcription factors, including
      JRE4 (otherwise known as GAME9), but the exact regulatory significance in planta
      of each factor has remained unaddressed. Here, via TILLING-based screening of an
      EMS-mutagenized tomato population, we isolated a JRE4 loss-of-function line that
      carries an amino acid residue missense change in a region of the protein
      important for DNA binding. In this jre4 mutant, we observed downregulated
      expression of SGA biosynthetic genes and decreased SGA accumulation. Moreover,
      JRE4 overexpression stimulated SGA production. Further characterization of jre4
      plants revealed their increased susceptibility to the generalist herbivore
      Spodoptera litura larvae. This susceptibility illustrates that herbivory
      resistance is dependent on JRE4-mediated defense responses, which include SGA
      accumulation. Ethylene treatment attenuated the jasmonate-mediated JRE4
      expression induction and downstream SGA biosynthesis in tomato leaves and hairy
      roots. Overall, this study indicated that JRE4 functions as a primary master
      regulator of SGA biosynthesis, and thereby contributes toward plant defense
      against chewing insects.

PMID- 29569784
TI  - The CNPY2 enhances epithelial-mesenchymal transition via activating the
      AKT/GSK3beta pathway in non-small cell lung cancer.
AB  - The survival of non-small cell lung cancer (NSCLC) is poor due to high
      metastasis, and the indispensable step of metastasis includes epithelial
      mesenchymal transition (EMT). In the study, by analyzing the dataset of the
      Cancer Genome Atlas (TCGA), we found that the expression of Canopy homolog 2
      (CNPY2) is increased both in adenocarcinoma and squamous cell carcinoma, which is
      further confirmed in NSCLC tissues. Not only that, there is a negative
      correlation between CNPY2 and E-cadherin expression at mRNA level. Wound healing
      and transwell matrix penetration assay showed that overexpression of CNPY2
      promotes the capability for invasion and metastasis of NSCLC cells. Further
      analysis uncovered that overexpression of CNPY2 can activate the AKT/GSK3beta
      pathway, which leads to the inactivation of GSK-3beta. The inactivation of GSK
      3beta increases the level of Snail, and then decreases the expression of E
      cadherin to promote EMT. Eventually, inhibition of AKT suppresses the malignant
      transformation of CNPY2-upregulated cells. The above results suggest that CNPY2
      may be served as a novel therapeutic target to therapy the NSCLC.

PMID- 29569785
TI  - Sex- and age-adjusted prevalence estimates of five chronic inflammatory skin
      diseases in France: results of the " OBJECTIFS PEAU " study.
AB  - BACKGROUND: There are few population-based studies assessing the prevalence of
      skin diseases. OBJECTIVES: To estimate the prevalence of five chronic skin
      inflammatory diseases, i.e. atopic dermatitis (AD), psoriasis, alopecia areata
      (AA), vitiligo and hidradenitis suppurativa (HS) in France, using validated self
      diagnostic questionnaires. METHODS: Population-based study using a representative
      sample of the French general population aged more than 15 years and sampling with
      replacement design. All participants were asked (ii) to fill in a specific
      questionnaire including socio-demographic characteristics, (ii) to declare if
      they have been diagnosed with one or more skin problem or skin diseases during
      their life, and (iii) to fill in five validated self-reported questionnaires for
      AD, psoriasis, AA, vitiligo and HS. RESULTS: A total of 20.012 adult participants
      responded to the questionnaire of whom 9760 were men (48.8%) and 10.252 (51.2%)
      were women. We identified a prevalence of 4.65% for AD (931 individuals), 4.42%
      for psoriasis (885 individuals), 1.04% for AA (210 individuals), 0.46% for
      vitiligo (93 individuals) and 0.15% for HS (29 individuals), respectively.
      LIMITATIONS: Questionnaire-based study and possible disease misclassifications.
      CONCLUSION: This is the largest population-based study aiming to estimate the
      prevalence of five chronic skin inflammatory diseases.

PMID- 29569786
TI  - Propofol prevents IL-13-induced epithelial-mesenchymal transition in human
      colorectal cancer cells.
AB  - Accumulating evidence showed that cytokines are involved in the development of
      cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote
      metastasis in colorectal cancer, providing a promising therapeutic target for
      cancer patients. Interestingly, recent studies showed that propofol, one of most
      common intravenous anesthetic agent, may have antitumor function in different
      cancer type. However, the impact of propofol on colorectal cancer and IL-13
      induced epithelial-mesenchymal transition remains unknown. Herein, we found that
      propofol can effectively suppress cell proliferation in colorectal cell lines RKO
      and SW480 cells by using MTT assay. Furthermore, wound healing assay and
      migration assay demonstrated that propofol has the ability to inhibit epithelial
      mesenchymal transition that induced by IL-13 in RKO and SW480 cells.
      Mechanistically, we found propofol treatment causes up-regulation of miR-361 and
      miR-135b, that suppress expression of STAT6 and thereafter leads to the
      inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the
      first time demonstrated that propofol may serve as a novel therapeutic drug for
      targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal
      cancer was impaired by propofol through miR-361 and miR-135b.

PMID- 29569787
TI  - Are we any nearer to clinically useful pretransplant prediction of post
      transplant outcomes?

PMID- 29569788
TI  - Large uncertainty in carbon uptake potential of land-based climate-change
      mitigation efforts.
AB  - Most climate mitigation scenarios involve negative emissions, especially those
      that aim to limit global temperature increase to 2 degrees C or less. However,
      the carbon uptake potential in land-based climate change mitigation efforts is
      highly uncertain. Here, we address this uncertainty by using two land-based
      mitigation scenarios from two land-use models (IMAGE and MAgPIE) as input to four
      dynamic global vegetation models (DGVMs; LPJ-GUESS, ORCHIDEE, JULES, LPJmL). Each
      of the four combinations of land-use models and mitigation scenarios aimed for a
      cumulative carbon uptake of ~130 GtC by the end of the century, achieved either
      via the cultivation of bioenergy crops combined with carbon capture and storage
      (BECCS) or avoided deforestation and afforestation (ADAFF). Results suggest large
      uncertainty in simulated future land demand and carbon uptake rates, depending on
      the assumptions related to land use and land management in the models. Total
      cumulative carbon uptake in the DGVMs is highly variable across mitigation
      scenarios, ranging between 19 and 130 GtC by year 2099. Only one out of the 16
      combinations of mitigation scenarios and DGVMs achieves an equivalent or higher
      carbon uptake than achieved in the land-use models. The large differences in
      carbon uptake between the DGVMs and their discrepancy against the carbon uptake
      in IMAGE and MAgPIE are mainly due to different model assumptions regarding
      bioenergy crop yields and due to the simulation of soil carbon response to land
      use change. Differences between land-use models and DGVMs regarding forest
      biomass and the rate of forest regrowth also have an impact, albeit smaller, on
      the results. Given the low confidence in simulated carbon uptake for a given land
      based mitigation scenario, and that negative emissions simulated by the DGVMs are
      typically lower than assumed in scenarios consistent with the 2 degrees C target,
      relying on negative emissions to mitigate climate change is a highly uncertain
      strategy.

PMID- 29569789
TI  - Testate amoeba records indicate regional 20th-century lowering of water tables in
      ombrotrophic peatlands in central-northern Alberta, Canada.
AB  - Testate amoebae are abundant in the surface layers of northern peatlands.
      Analysis of their fossilized shell (test) assemblages allows for reconstructions
      of local water-table depths (WTD). We have reconstructed WTD dynamics for five
      peat cores from peatlands ranging in distance from the Athabasca bituminous sands
      (ABS) region in western Canada. Amoeba assemblages were combined with plant
      macrofossil records, acid-insoluble ash (AIA) fluxes and instrumental climate
      data to identify drivers for environmental change. Two functional traits of
      testate amoebae, mixotrophy and the tendency to integrate xenogenic mineral
      matter in test construction, were quantified to infer possible effects of AIA
      flux on testate amoeba presence. Age-depth models showed the cores each covered
      at least the last ~315 years, with some spanning the last millennium. Testate
      amoeba assemblages were likely affected by permafrost development in two of the
      peatlands, yet the most important shift in assemblages was detected after 1960
      CE. This shift represents a significant apparent lowering of water tables in four
      out of five cores, with a mean drop of ~15 cm. Over the last 50 years,
      assemblages shifted towards more xerophilous taxa, a trend which was best
      explained by increasing Sphagnum s. Acutifolia and, to a lesser extent, mean
      summer temperature. This trend was most evident in the two cores from the sites
      located farthest away from the ABS region. AIA flux variations did not show a
      clear effect on mineral-agglutinating taxa, nor on S. s. Acutifolia presence. We
      therefore suggest the drying trend was forced by the establishment of S. s.
      Acutifolia, driven by enhanced productivity following regional warming. Such
      recent apparent drying of peatlands, which may only be reconstructed by
      appropriate indicators combined with high chronological control, may affect
      vulnerability to future burning and promote emissions of CO2 .

PMID- 29569790
TI  - Hypoxia-Activated Adipose Mesenchymal Stem Cells Prevents Irradiation-Induced
      Salivary Hypofunction by Enhanced Paracrine Effect Through Fibroblast Growth
      Factor 10.
AB  - To explore the effects and mechanisms of paracrine factors secreted from human
      adipose mesenchymal stem cell (hAdMSCs) that are activated by hypoxia on
      radioprotection against irradiation-induced salivary hypofunction in subjects
      undergoing radiotherapy for head and neck cancers. An organotypic spheroid
      coculture model to mimic irradiation (IR)-induced salivary hypofunction was set
      up for in vitro experiments. Human parotid gland epithelial cells were organized
      to form three-dimensional (3D) acinus-like spheroids on growth factor reduced 
      Matrigel. Cellular, structural, and functional damage following IR were examined
      after cells were cocultured with hAdMSCs preconditioned with either normoxia
      (hAdMSCNMX ) or hypoxia (hAdMSCHPX ). A key paracrine factor secreted by
      hAdMSCsHPX was identified by high-throughput microarray-based enzyme-linked
      immunosorbent assay. Molecular mechanisms and signaling pathways on
      radioprotection were explored. Therapeutic effects of hAdMSCsHPX were evaluated
      after in vivo transplant into mice with IR-induced salivary hypofunction. In our
      3D coculture experiment, hAdMSCsHPX significantly enhanced radioresistance of
      spheroidal human parotid epithelial cells, and led to greater preservation of
      salivary epithelial integrity and acinar secretory function relative to
      hAdMSCsNMX . Coculture with hAdMSCsHPX promoted FGFR expression and suppressed
      FGFR diminished antiapoptotic activity of hAdMSCsHPX . Among FGFR-binding
      secreted factors, we found that fibroblast growth factor 10 (FGF10) contributed
      to therapeutic effects of hAdMSCsHPX by enhancing antiapoptotic effect, which was
      dependent on FGFR-PI3K signaling. An in vivo transplant of hAdMSCsHPX into
      irradiated salivary glands of mice reversed IR-induced salivary hypofunction
      where hAdMSC-released FGF10 contributed to tissue remodeling. Our results suggest
      that hAdMSCsHPX protect salivary glands from IR-induced apoptosis and preserve
      acinar structure and functions by activation of FGFR-PI3K signaling via actions
      of hAdMSC-secreted factors, including FGF10. Stem Cells 2018;36:1020-1032.

PMID- 29569791
TI  - Hyperbaric oxygen as a treatment modality in cyclophosphamide-induced hemorrhagic
      cystitis.
AB  - Late-onset HC is a well-recognized complication associated with
      cyclophosphamide/acrolein-induced toxicity. It poses a management challenge when
      hyperhydration and bladder irrigation do not result in clinical improvement as
      desired. The data regarding use of hyperbaric oxygen therapy (HBO2) as an early
      treatment modality in this clinical setting are limited. We present 2 cases, that
      were refractory to hyperhydration and bladder irrigation but responded to HBO2.
      They were treated with 20-30 daily sessions over weekdays with 100% oxygen for 90
      minutes at 2 atmospheric pressure units (2 atm). Both patients reported improved
      symptoms within the first 15 sessions, and hematuria diminished by 20 sessions.
      Hyperbaric oxygen is a less invasive, outpatient therapy that is effective for
      treatment of HC and is tolerated well by young patients.

PMID- 29569792
TI  - Downregulation of miR-491-5p promotes gastric cancer metastasis by regulating
      SNAIL and FGFR4.
AB  - Gastric cancer (GC) is among the most fatal cancers in China. MicroRNAs (miRNAs)
      are versatile regulators during GC development and progression. miR-491-5p has
      been demonstrated to act as a tumor suppressor in several types of cancer.
      However, the role of miR-491-5p in GC metastasis remains unknown. Here, we found
      that miR-491-5p was significantly decreased in GC tissues compared with adjacent
      non-cancerous tissues, and low miR-491-5p level was associated with large tumor
      size. Overexpression of miR-491-5p significantly suppressed GC cell epithelial-to
      mesenchymal transition (EMT) and tumor metastasis in vitro and in vivo.
      Mechanistically, SNAIL was identified as a direct target of miR-491-5p. The
      silencing of SNAIL phenocopied the tumor suppressive function of miR-491-5p,
      whereas re-expression of SNAIL in GC cells rescued the EMT markers and cell
      migratory ability that were inhibited by miR-491-5p. In addition, miR-491-5p
      inhibited FGFR4 indirectly. Inhibition of FGFR4 also decreased the SNAIL level
      and impaired EMT and cell migration. Taken together, these findings indicate that
      downregulation of miR-491-5p promoted GC metastasis by inducing EMT via
      regulation of SNAIL and FGFR4.

PMID- 29569793
TI  - The effect of sleep hygiene education and relaxation exercises on insomnia among
      postmenopausal women: A randomized clinical trial.
AB  - AIM: This study used a randomized controlled trial model to determine the effect
      of progressive relaxation exercises and sleep hygiene training given to
      postmenopausal women with insomnia. METHODS: A total of 161 postmenopausal women
      with insomnia were recruited and randomly assigned to experimental (n = 81) and
      control (n = 80) groups. The experimental group received sleep hygiene and
      progressive relaxation exercise training, but the control group only received
      routine health care. The relaxation exercise training was repeated once a week
      for 8 weeks. The study determined the effect of the intervention on insomnia
      symptoms. The data were collected between 15 June and 15 September 2015 and
      evaluated using descriptive statistics, independent samples t-test, chi-squared
      test, and Cronbach alpha analysis. RESULTS: The mean (SD) score of the
      experimental group on the Women's Health Initiative Insomnia Rating Scale was
      14.03 (3.4) pretest and 7.09 (3.4) posttest. The difference between the pretest
      and posttest scores was statistically significant (P < .001), as was the
      difference between the rates of insomnia symptoms between the groups posttest (P
      < .001). CONCLUSION: The findings of study suggest that nurses teaching
      progressive relaxation exercises and sleep hygiene would benefit postmenopausal
      women who suffer from insomnia.

PMID- 29569794
TI  - Nitrogen deposition outweighs climatic variability in driving annual growth rate
      of canopy beech trees: Evidence from long-term growth reconstruction across a
      geographic gradient.
AB  - In this study, we investigated the role of climatic variability and atmospheric
      nitrogen deposition in driving long-term tree growth in canopy beech trees along
      a geographic gradient in the montane belt of the Italian peninsula, from the Alps
      to the southern Apennines. We sampled dominant trees at different developmental
      stages (from young to mature tree cohorts, with tree ages spanning from 35 to 160
      years) and used stem analysis to infer historic reconstruction of tree volume and
      dominant height. Annual growth volume (GV ) and height (GH ) variability were
      related to annual variability in model simulated atmospheric nitrogen deposition
      and site-specific climatic variables, (i.e. mean annual temperature, total annual
      precipitation, mean growing period temperature, total growing period
      precipitation, and standard precipitation evapotranspiration index) and
      atmospheric CO2 concentration, including tree cambial age among growth
      predictors. Generalized additive models (GAM), linear mixed-effects models (LMM),
      and Bayesian regression models (BRM) were independently employed to assess
      explanatory variables. The main results from our study were as follows: (i) tree
      age was the main explanatory variable for long-term growth variability; (ii) GAM,
      LMM, and BRM results consistently indicated climatic variables and CO2 effects on
      GV and GH were weak, therefore evidence of recent climatic variability influence
      on beech annual growth rates was limited in the montane belt of the Italian
      peninsula; (iii) instead, significant positive nitrogen deposition (Ndep )
      effects were repeatedly observed in GV and GH ; the positive effects of Ndep on
      canopy height growth rates, which tended to level off at Ndep values greater than
      approximately 1.0 g m-2  y-1 , were interpreted as positive impacts on forest
      stand above-ground net productivity at the selected study sites.

PMID- 29569796
TI  - Point: Moral distress can indicate inappropriate care at end-of-Life.

PMID- 29569795
TI  - Induction of chemokine (C-C motif) ligand 5 by Epstein-Barr virus infection
      enhances tumor angiogenesis in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr
      virus (EBV) infection and is known to be highly vascularized. Previous studies
      have suggested that EBV oncoproteins contribute to NPC angiogenesis. However, the
      regulatory network of EBV in angiogenesis still remains elusive. Herein, we
      reveal a novel mechanism of EBV-induced angiogenesis in NPC. First, we showed
      that EBV-infected NPC cell lines generated larger tumors with more microvessels
      in mouse xenograft models. Subsequent proteomic analysis revealed that EBV
      infection increased the expression of a series of angiogenic factors, including
      chemokine (C-C motif) ligand 5 (CCL5). We then proved that CCL5 was a target of
      EBV in inducing tumor angiogenesis and growth. Further investigation through
      transcriptome analysis indicated that the pro-angiogenic function of CCL5 might
      be mediated by the PI3K/AKT pathway. Furthermore, we confirmed that activation of
      the PI3K/AKT and hypoxia-inducible factor-1alpha pathways was essential for CCL5
      promoted angiogenesis. Finally, the immunohistochemical analysis of human NPC
      specimens also showed that CCL5 was correlated with angiogenesis. Taken together,
      our study identifies CCL5 as a key EBV-regulated molecular driver that promotes
      NPC angiogenesis, suggesting it as a potential therapeutic target.

PMID- 29569797
TI  - Follistatin-Like 3 Enhances the Function of Endothelial Cells Derived from
      Pluripotent Stem Cells by Facilitating beta-Catenin Nuclear Translocation Through
      Inhibition of Glycogen Synthase Kinase-3beta Activity.
AB  - The fight against vascular disease requires functional endothelial cells (ECs)
      which could be provided by differentiation of induced Pluripotent Stem Cells (iPS
      Cells) in great numbers for use in the clinic. However, the great promise of the
      generated ECs (iPS-ECs) in therapy is often restricted due to the challenge in
      iPS-ECs preserving their phenotype and function. We identified that Follistatin
      Like 3 (FSTL3) is highly expressed in iPS-ECs, and, as such, we sought to clarify
      its possible role in retaining and improving iPS-ECs function and phenotype,
      which are crucial in increasing the cells' potential as a therapeutic tool. We
      overexpressed FSTL3 in iPS-ECs and found that FSTL3 could induce and enhance
      endothelial features by facilitating beta-catenin nuclear translocation through
      inhibition of glycogen synthase kinase-3beta activity and induction of Endothelin
      1. The angiogenic potential of FSTL3 was also confirmed both in vitro and in
      vivo. When iPS-ECs overexpressing FSTL3 were subcutaneously injected in in vivo
      angiogenic model or intramuscularly injected in a hind limb ischemia NOD.CB17
      Prkdcscid/NcrCrl SCID mice model, FSTL3 significantly induced angiogenesis and
      blood flow recovery, respectively. This study, for the first time, demonstrates
      that FSTL3 can greatly enhance the function and maturity of iPS-ECs. It advances
      our understanding of iPS-ECs and identifies a novel pathway that can be applied
      in cell therapy. These findings could therefore help improve efficiency and
      generation of therapeutically relevant numbers of ECs for use in patient-specific
      cell-based therapies. In addition, it can be particularly useful toward the
      treatment of vascular diseases instigated by EC dysfunction. Stem Cells
      2018;36:1033-1044.

PMID- 29569798
TI  - Vascular plant-mediated controls on atmospheric carbon assimilation and peat
      carbon decomposition under climate change.
AB  - Climate change can alter peatland plant community composition by promoting the
      growth of vascular plants. How such vegetation change affects peatland carbon
      dynamics remains, however, unclear. In order to assess the effect of vegetation
      change on carbon uptake and release, we performed a vascular plant-removal
      experiment in two Sphagnum-dominated peatlands that represent contrasting stages
      of natural vegetation succession along a climatic gradient. Periodic measurements
      of net ecosystem CO2 exchange revealed that vascular plants play a crucial role
      in assuring the potential for net carbon uptake, particularly with a warmer
      climate. The presence of vascular plants, however, also increased ecosystem
      respiration, and by using the seasonal variation of respired CO2 radiocarbon
      (bomb-14 C) signature we demonstrate an enhanced heterotrophic decomposition of
      peat carbon due to rhizosphere priming. The observed rhizosphere priming of peat
      carbon decomposition was matched by more advanced humification of dissolved
      organic matter, which remained apparent beyond the plant growing season. Our
      results underline the relevance of rhizosphere priming in peatlands, especially
      when assessing the future carbon sink function of peatlands undergoing a shift in
      vegetation community composition in association with climate change.

PMID- 29569799
TI  - How will climate novelty influence ecological forecasts? Using the Quaternary to
      assess future reliability.
AB  - Future climates are projected to be highly novel relative to recent climates.
      Climate novelty challenges models that correlate ecological patterns to climate
      variables and then use these relationships to forecast ecological responses to
      future climate change. Here, we quantify the magnitude and ecological
      significance of future climate novelty by comparing it to novel climates over the
      past 21,000 years in North America. We then use relationships between model
      performance and climate novelty derived from the fossil pollen record from
      eastern North America to estimate the expected decrease in predictive skill of
      ecological forecasting models as future climate novelty increases. We show that,
      in the high emissions scenario (RCP 8.5) and by late 21st century, future climate
      novelty is similar to or higher than peak levels of climate novelty over the last
      21,000 years. The accuracy of ecological forecasting models is projected to
      decline steadily over the coming decades in response to increasing climate
      novelty, although models that incorporate co-occurrences among species may retain
      somewhat higher predictive skill. In addition to quantifying future climate
      novelty in the context of late Quaternary climate change, this work underscores
      the challenges of making reliable forecasts to an increasingly novel future,
      while highlighting the need to assess potential avenues for improvement, such as
      increased reliance on geological analogs for future novel climates and improving
      existing models by pooling data through time and incorporating assemblage-level
      information.

PMID- 29569800
TI  - Time lag and negative responses of forest greenness and tree growth to warming
      over circumboreal forests.
AB  - The terrestrial forest ecosystems in the northern high latitude region have been
      experiencing significant warming rates over several decades. These forests are
      considered crucial to the climate system and global carbon cycle and are
      particularly vulnerable to climate change. To obtain an improved estimate of the
      response of vegetation activity, e.g., forest greenness and tree growth, to
      climate change, we investigated spatiotemporal variations in two independent data
      sets containing the dendroecological information for this region over the past 30
      years. These indices are the normalized difference vegetation index (NDVI3g) and
      the tree-ring width index (RWI), both of which showed significant spatial
      variability in past trends and responses to climate changes. These trends and
      responses to climate change differed significantly in the ecosystems of the
      circumarctic (latitude higher than 67 degrees N) and the circumboreal forests
      (latitude higher and lower than 50 degrees N and 67 degrees N, respectively), but
      the way in which they differed was relatively similar in the NDVI3g and the RWI.
      In the circumarctic ecosystem, the climate variables of the current summer were
      the main climatic drivers for the positive response to the increase in
      temperatures showed by both the NDVI3g and the RWI indices. On the other hand, in
      the circumboreal forest ecosystem, the climate variables of the previous year
      (from summer to winter) were also important climatic drivers for both the NDVI3g
      and the RWI. Importantly, both indices showed that the temperatures in the
      previous year negatively affected the ecosystem. Although such negative responses
      to warming did not necessarily lead to a past negative linear trend in the NDVI3g
      and the RWI over the past 30 years, future climate warming could potentially
      cause severe reduction in forest greenness and tree growth in the circumboreal
      forest ecosystem.

PMID- 29569801
TI  - Anterior insula hyperactivation in ADHD when faced with distracting negative
      stimuli.
AB  - Patients with attention deficit hyperactivity disorder (ADHD) suffer from poor
      emotion regulation that might arise from problems in the distribution of
      attentional resources when confronted with emotional distractors. Previous
      studies investigating the neurocognitive basis of these problems remain
      inconclusive. Moreover, most of these studies did not exclude participants with
      comorbidity, particularly of conduct or oppositional defiant disorder. The aim of
      this study was to assess alterations in fronto-limbic activation in ADHD
      adolescents specifically during negative distractors in an emotional attention
      task. For this purpose, we used functional magnetic resonance imaging to assess
      25 boys with noncomorbid ADHD and 25 typically developing (TD) boys while they
      performed an emotional attention task with positive, negative, and neutral
      emotional distractors. Boys with ADHD had increased activation relative to TD
      boys specifically during the negative valenced stimuli in an emotional processing
      network comprising left anterior insula reaching into the inferior frontal gyrus.
      The findings suggest altered salience processing in ADHD of negative valenced
      emotional stimuli that may lead to higher distractibility in ADHD specifically
      when faced with negative emotional distractors.

PMID- 29569802
TI  - Explaining the doubling of N2 O emissions under elevated CO2 in the Giessen FACE
      via in-field 15 N tracing.
AB  - Rising atmospheric CO2 concentrations are expected to increase nitrous oxide (N2
      O) emissions from soils via changes in microbial nitrogen (N) transformations.
      Several studies have shown that N2 O emission increases under elevated
      atmospheric CO2 (eCO2 ), but the underlying processes are not yet fully
      understood. Here, we present results showing changes in soil N transformation
      dynamics from the Giessen Free Air CO2 Enrichment (GiFACE): a permanent grassland
      that has been exposed to eCO2 , +20% relative to ambient concentrations (aCO2 ),
      for 15 years. We applied in the field an ammonium-nitrate fertilizer solution, in
      which either ammonium (NH4+) or nitrate (NO3-) was labelled with 15 N. The
      simultaneous gross N transformation rates were analysed with a 15 N tracing model
      and a solver method. The results confirmed that after 15 years of eCO2 the N2 O
      emissions under eCO2 were still more than twofold higher than under aCO2 . The
      tracing model results indicated that plant uptake of NH4+ did not differ between
      treatments, but uptake of NO3- was significantly reduced under eCO2 . However,
      the NH4+ and NO3- availability increased slightly under eCO2 . The N2 O isotopic
      signature indicated that under eCO2 the sources of the additional emissions,
      8,407 MUg N2 O-N/m2 during the first 58 days after labelling, were associated
      with NO3- reduction (+2.0%), NH4+ oxidation (+11.1%) and organic N oxidation
      (+86.9%). We presume that increased plant growth and root exudation under eCO2
      provided an additional source of bioavailable supply of energy that triggered as
      a priming effect the stimulation of microbial soil organic matter (SOM)
      mineralization and fostered the activity of the bacterial nitrite reductase. The
      resulting increase in incomplete denitrification and therefore an increased N2
      O:N2 emission ratio, explains the doubling of N2 O emissions. If this occurs over
      a wide area of grasslands in the future, this positive feedback reaction may
      significantly accelerate climate change.

PMID- 29569803
TI  - Elevated CO2 did not affect the hydrological balance of a mature native
      Eucalyptus woodland.
AB  - Elevated atmospheric CO2 concentration (eCa ) might reduce forest water-use, due
      to decreased transpiration, following partial stomatal closure, thus enhancing
      water-use efficiency and productivity at low water availability. If
      evapotranspiration (Et ) is reduced, it may subsequently increase soil water
      storage (DeltaS) or surface runoff (R) and drainage (Dg ), although these could
      be offset or even reversed by changes in vegetation structure, mainly increased
      leaf area index (L). To understand the effect of eCa in a water-limited
      ecosystem, we tested whether 2 years of eCa (~40% increase) affected the
      hydrological partitioning in a mature water-limited Eucalyptus woodland exposed
      to Free-Air CO2 Enrichment (FACE). This timeframe allowed us to evaluate whether
      physiological effects of eCa reduced stand water-use irrespective of L, which was
      unaffected by eCa in this timeframe. We hypothesized that eCa would reduce tree
      canopy transpiration (Etree ), but excess water from reduced Etree would be lost
      via increased soil evaporation and understory transpiration (Efloor ) with no
      increase in DeltaS, R or Dg . We computed Et , DeltaS, R and Dg from measurements
      of sapflow velocity, L, soil water content (theta), understory micrometeorology,
      throughfall and stemflow. We found that eCa did not affect Etree , Efloor ,
      DeltaS or theta at any depth (to 4.5 m) over the experimental period. We closed
      the water balance for dry seasons with no differences in the partitioning to R
      and Dg between Ca levels. Soil temperature and theta were the main drivers of
      Efloor while vapour pressure deficit-controlled Etree , though eCa did not
      significantly affect any of these relationships. Our results suggest that in the
      short-term, eCa does not significantly affect ecosystem water-use at this site.
      We conclude that water-savings under eCa mediated by either direct effects on
      plant transpiration or by indirect effects via changes in L or soil moisture
      availability are unlikely in water-limited mature eucalypt woodlands.

PMID- 29569804
TI  - In Vitro Fusion of Normal and Neoplastic Breast Epithelial Cells with Human
      Mesenchymal Stroma/Stem Cells Partially Involves Tumor Necrosis Factor Receptor
      Signaling.
AB  - Formation of hybrid cells by "accidental cell fusion" of normal and neoplastic
      breast epithelial cells with local tissue-associated mesenchymal stroma/stem-like
      cells (MSC) in an inflammatory microenvironment can generate new cancer cell
      populations whereby molecular signaling mechanisms of this process remain
      unclear. Fusions of lentiviral enhanced green fluorescent protein-labeled MSC
      with mcherry-labeled breast epithelial cells were quantified and effects of tumor
      necrosis factor alpha (TNF-alpha) and receptor downstream signaling were
      investigated. Cocultures of MSC with normal human mammary epithelial cells, with
      neoplastic MCF10A, or with MDA-MB-231 or MCF7 breast cancer cells demonstrated
      hybrid cell formation between 0.1% and about 2% of the populations within 72
      hours, whereby the fusion process occurred in less than 5 minutes. Addition of
      the pro-inflammatory cytokine TNF-alpha significantly enhanced MCF10A-MSC cell
      fusion. Small-interfering RNA (siRNA) knockdown experiments revealed an
      involvement of tumor necrosis factor (TNF) receptor-1 and -2 in this process.
      This was also substantiated by siRNA knockdown of tumor necrosis factor receptor
      type 1-associated death domain which abolished TNF-alpha-stimulated fusion. While
      TNF receptor signaling can be relayed via the Mitogen-activated protein kinase 8
      (MAPK8), NF-kappaB or cell death pathways, examination of further downstream
      signaling exhibited little if any effects of MAPK8 or RelA (p65) on TNF-alpha
      mediated cell fusion, respectively. These data suggested that cell fusion between
      MSC and MCF10A breast epithelial cells can be stimulated by TNF-alpha involving
      TNF receptor-activated cell death pathways or additional NF-kappaB signaling.
      Stem Cells 2018;36:977-989.

PMID- 29569805
TI  - Isolated cutaneous mucormycosis in a pediatric renal transplant recipient.
AB  - Mucormycosis is a rare and potentially life-threatening infection, typically
      affecting immunocompromised hosts. We report a case of an adolescent boy who
      developed primary isolated cutaneous mucormycosis in the early period following
      kidney transplantation. Surgical excision was performed using intraoperative
      fungal staining to obtain clear margins, followed by topical and systemic
      antifungal therapy. A skin graft was then applied to the excised area with good
      healing, and the patient made a full recovery.

PMID- 29569806
TI  - Effect of everolimus on skin lesions in patients treated for subependymal giant
      cell astrocytoma and renal angiomyolipoma: final 4-year results from the
      randomized EXIST-1 and EXIST-2 studies.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder associated
      with tumour growth in various organs, including the brain, kidneys, heart and
      skin. Cutaneous lesions are prevalent manifestations of TSC, occurring in up to
      90% of patients. Oral mammalian target of rapamycin inhibitors, such as
      everolimus, is believed to be effective for treatment of TSC-associated lesions
      because they act on the underlying disease pathophysiology. OBJECTIVE: We
      evaluated the long-term effect of oral everolimus on TSC-associated skin lesions
      as a secondary objective in the phase III studies EXIST-1 (NCT00789828) and EXIST
      2 (NCT00790400) after approximately 4 years of treatment. MATERIALS AND METHODS:
      Everolimus was dosed 4.5 mg/m2 /day (titrated to trough 5-15 ng/mL) in patients
      with TSC-associated subependymal giant cell astrocytoma in EXIST-1, and 10 mg/day
      initially in adult patients with TSC- or sporadic lymphangioleiomyomatosis
      associated renal angiomyolipoma in EXIST-2. Following positive results from the
      core phase, remaining patients were offered open-label everolimus in an
      extension. Skin lesion response rate was the proportion of patients achieving
      complete or partial clinical response. RESULTS: A total of 105 patients in EXIST
      1 and 107 in EXIST-2 received everolimus and had >=1 skin lesion at baseline.
      Skin lesion response rate (95% confidence interval) was 58.1% (48.1-67.7%) in
      EXIST-1 and 68.2% (58.5-76.9%) in EXIST-2; most were partial responses. At week
      192 (EXIST-1: n = 55; EXIST-2: n = 56), 69% and 66% had a response. Most common
      drug-related adverse event was stomatitis (41-45%). CONCLUSION: Oral everolimus
      improved TSC-related skin lesions, with responses sustained over 4 years of
      treatment in EXIST-1 and EXIST-2.

PMID- 29569807
TI  - Coral bleaching is linked to the capacity of the animal host to supply essential
      metals to the symbionts.
AB  - Massive coral bleaching events result in extensive coral loss throughout the
      world. These events are mainly caused by seawater warming, but are exacerbated by
      the subsequent decrease in nutrient availability in surface waters. It has
      therefore been shown that nitrogen, phosphorus or iron limitation contribute to
      the underlying conditions by which thermal stress induces coral bleaching.
      Generally, information on the trophic ecology of trace elements (micronutrients)
      in corals, and on how they modulate the coral response to thermal stress is
      lacking. Here, we demonstrate for the first time that heterotrophic feeding (i.e.
      the capture of zooplankton prey by the coral host) and thermal stress induce
      significant changes in micro element concentrations and isotopic signatures of
      the scleractinian coral Stylophora pistillata. The results obtained first reveal
      that coral symbionts are the major sink for the heterotrophically acquired
      micronutrients and accumulate manganese, magnesium and iron from the food. These
      metals are involved in photosynthesis and antioxidant protection. In addition, we
      show that fed corals can maintain high micronutrient concentrations in the host
      tissue during thermal stress and do not bleach, whereas unfed corals experience a
      significant decrease in copper, zinc, boron, calcium and magnesium in the host
      tissue and bleach. In addition, the significant increase in delta65 Cu and
      delta66 Zn signature of symbionts and host tissue at high temperature suggests
      that these isotopic compositions are good proxy for stress in corals. Overall,
      present findings highlight a new way in which coral heterotrophy and
      micronutrient availability contribute to coral resistance to global warming and
      bleaching.

PMID- 29569809
TI  - Commentary on 'Changing prevalence of diabetes mellitus in bullous pemphigoid: it
      is the dipeptidyl peptidase-4 inhibitors'.

PMID- 29569808
TI  - A voxel-based asymmetry study of the relationship between hemispheric asymmetry
      and language dominance in Wada tested patients.
AB  - Determining the anatomical basis of hemispheric language dominance (HLD) remains
      an important scientific endeavor. The Wada test remains the gold standard test
      for HLD and provides a unique opportunity to determine the relationship between
      HLD and hemispheric structural asymmetries on MRI. In this study, we applied a
      whole-brain voxel-based asymmetry (VBA) approach to determine the relationship
      between interhemispheric structural asymmetries and HLD in a large consecutive
      sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10
      (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty-four
      controls were also studied. Right-handed controls and right-handed patients with
      left HLD had comparable structural brain asymmetries in cortical, subcortical,
      and cerebellar regions that have previously been documented in healthy people.
      However, these patients and controls differed in structural asymmetry of the
      mesial temporal lobe and a circumscribed region in the superior temporal gyrus,
      suggesting that only asymmetries of these regions were due to brain alterations
      caused by epilepsy. Additional comparisons between patients with left and right
      HLD, matched for type and location of epilepsy, revealed that structural
      asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal
      cortex, ventral temporo-occipital cortex, mesial somatosensory cortex, and mesial
      cerebellum were significantly associated with the side of HLD. Patients with
      right HLD and bilateral language representation were significantly less right
      handed. These results suggest that structural asymmetries of an insular-fronto
      temporal network may be related to HLD.

PMID- 29569810
TI  - A case report of fatal disseminated Mycobacterium colombiense infection in a
      renal transplant recipient.
AB  - We report the first case of disseminated Mycobacterium colombiense infection in a
      solid organ transplant recipient. Co-infection with Cryptococcus neoformans led
      to fatal multisystem organ failure. We review the pathogen and host factors
      contributing to these opportunistic infections.

PMID- 29569811
TI  - A novel podoplanin-GFPCre mouse strain for gene deletion in lymphatic endothelial
      cells.
AB  - The lymphatic vascular system is a one-direction network of thin-walled
      capillaries and larger vessels covered by a continuous layer of endothelial cells
      responsible for maintaining fluid homeostasis. Some of the main functions of the
      lymphatic vasculature are to drain fluid from the extracellular spaces and return
      it back to the blood circulation, lipid absorption from the intestinal tract, and
      transport of immune cells to lymphoid organs. A number of genes controlling the
      development of the mammalian lymphatic vasculature have been identified in the
      last few years, and their functional roles started to be characterized using gene
      inactivation approaches in mice. Unfortunately, only few mouse Cre strains
      relatively specific for lymphatic endothelial cells (LECs) are currently
      available. In this article, we report the generation of a novel Podoplanin (Pdpn)
      GFPCre transgenic mouse strain using its 5' regulatory region. Pdpn encodes a
      transmembrane mucin-type O-glycoprotein that is expressed on the surface of
      embryonic and postnatal LECs, in addition to few other cell types. Our detailed
      characterization of this novel strain indicates that it will be a valuable
      additional genetic tool for the analysis of gene function in LECs.

PMID- 29569812
TI  - Ofatumumab in post-transplantation recurrence of a pediatric steroid-resistant
      idiopathic nephrotic syndrome.
AB  - Treatment of SRNS is a challenge. Antiproliferative agents and depleting
      antibodies have been reported to be effective. However, these agents are not
      always successful, and use of ofatumumab could provide a different treatment
      option. Our patient was diagnosed with a SRNS at 5 years of age. She developed
      ESRD, with FSGS. This was cause for a first renal transplantation. The NS
      relapsed, leading to loss of the graft, and a second renal transplantation was
      performed. Due to the recurrence of the NS, IAds were initiated and led to a
      complete remission. Our patient remained dependent on IAds, however, despite
      treatments with calcineurin inhibitors, corticosteroids, rituximab, and
      abatacept. Ofatumumab was introduced and led to a remission, thus allowing
      cessation of the IAd treatment. Another infusion of ofatumumab was administered 8
      months after the last one, due to the recurrence of the NS and a renewed increase
      in B cells. Although it did not result in a complete remission, the proteinuria
      was stabilized in the absence of IAds. Ofatumumab may be an alternative treatment
      for post-transplantation rituximab-resistant SRNS, although this needs to be
      confirmed by further studies.

PMID- 29569813
TI  - Prospective monitoring of adenovirus infection and type analysis after allogeneic
      hematopoietic cell transplantation: A single-center study in Korea.
AB  - BACKGROUND: Epidemiologic studies of human adenovirus (HAdV) in allogeneic
      hematopoietic cell transplantation (HCT) recipients have been conducted mostly in
      European countries where HAdV 2 (species C) has been most prevalent in the
      community. The main objective of this study was to investigate the epidemiology
      and the characteristics of HAdV infection in Korean allogeneic HCT recipients
      (<19 years). METHODS: In a prospective study from April 2012 to September 2015,
      HAdV in blood, urine, and stool specimens were monitored weekly from
      transplantation to day 100 or after if clinically suspected. HAdV infection was
      defined as positive HAdV PCR result in any specimens regardless of symptoms.
      RESULTS: A total of 1734 specimens were collected from 57 consecutively enrolled
      recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was
      10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The
      median onset time from HCT to viremia was 221 days (range, 7-596 days). All
      viremia cases were caused by only HAdV 3 (species B), whereas several types were
      detected in stool. Among patients with HAdV infection, lower absolute lymphocyte
      counts and extensive chronic graft-vs-host disease were associated with viremia
      (P = .028 and P = .006, respectively). CONCLUSIONS: Compared to western studies,
      this study demonstrated a lower incidence and delayed onset of HAdV infections
      and HAdV 3 was most prevalent in Korea.

PMID- 29569814
TI  - Molecular cloning, characterization, and expression profiles of the Sox3 gene in
      Chinese loach Paramisgurnus dabryanus.
AB  - A number of studies have established that in vertebrates, Sox3 is involved in a
      wide range of developmental processes, including sex differentiation and
      neurogenesis. However, the exact functions of the Sox3 gene have not been
      documented so far in teleosts. Here, we cloned the full length cDNA of Sox3 from
      the teleost fish, Paramisgurnus dabryanus, which we designated PdSox3. Sequence
      analysis revealed that PdSox3 encodes a hydrophilic protein, and shares high
      homology with Sox3 in other species, ranging from mammals to fishes. Quantitative
      real-time reverse transcription PCR, and in situ hybridization showed that PdSox3
      is consistently expressed during embryogenesis, mainly localized in the
      developing central nervous system. Tissue distribution analyses revealed that
      PdSox3 is abundant in the adult brain, especially in particle cell layer.
      Furthermore, PdSox3 expression was higher in gonads, in primary spermatocyte
      cells, primary oocytes, and previtellogenic oocyte cells. All of these results
      suggest that PdSox3 plays an important role in early embryonic development, in
      particular the formation and development of the nervous system, and gonad
      development, similarly to other vertebrates. This is the first report describing
      Sox3 gene expression from this species, and the results are necessary to provide
      fundamental information on both the functional and evolutionary role of Sox3
      across different species.

PMID- 29569815
TI  - Paradoxical immune reconstitution inflammatory syndrome associated with
      disseminated tuberculosis infection in an unrelated donor cord blood transplant
      recipient.
AB  - Tuberculosis (TB) is an infrequent infection after hematopoietic cell transplant
      (HCT), with associated mortality up to 30%. The utility of universal screening
      for latent TB in HCT candidates is controversial due to the lack of sensitive
      screening tests. We describe a case of disseminated TB infection complicated by
      immune reconstitution inflammatory syndrome in an adult double unit umbilical
      cord blood transplant recipient who originated from the United Arab Emirates.

PMID- 29569816
TI  - Big (Bio)Chemical Data Mining Using Chemometric Methods: A Need for Chemists.
AB  - This review aims to demonstrate abilities to analyze Big (Bio)Chemical Data
      (BBCD) with multivariate chemometric methods and to show some of the more
      important challenges of modern analytical researches. In this review, the
      capabilities and versatility of chemometric methods will be discussed in light of
      the BBCD challenges that are being encountered in chromatographic, spectroscopic
      and hyperspectral imaging measurements, with an emphasis on their application to
      omics sciences. In addition, insights and perspectives on how to address the
      analysis of BBCD are provided along with a discussion of the procedures necessary
      to obtain more reliable qualitative and quantitative results. In this review, the
      importance of Big Data and of their relevance to (bio)chemistry are first
      discussed. Then, analytical tools which can produce BBCD are presented as well as
      some basics needed to understand prospects and limitations of chemometric
      techniques when they are applied to BBCD are given. Finally, the significance of
      the combination of chemometric approaches with BBCD analysis in different
      chemical disciplines is highlighted with some examples. In this paper, we have
      tried to cover some of the applications of big data analysis in the
      (bio)chemistry field. However, this coverage is not extensive covering everything
      done in the field.

PMID- 29569817
TI  - In vitro and in vivo evaluation of novel biodegradable Mg-Ag-Y alloys for use as
      resorbable bone fixation implant.
AB  - Magnesium (Mg) alloy is gaining more interest because of its degradability and
      osteogenic potential. Still, it has some deficiencies, such as its rapid
      degradation rate, insufficient mechanical property. This research aimed to design
      a novel biodegradable Mg-argentum (Ag)-yttrium (Y) alloy, and Y was added to
      improve degradable and mechanical property. Mg-Ag-Y alloys were characterized for
      mechanical features, practicabilities in vitro and in vivo. The mechanical
      features results shown that this novel component was similar to native bone
      tissue in elastic moduli, tensile, and compressive stress. Then mesenchymal stem
      cells (MSCs) were seeded in alloys to assess cell toxicity in vitro. The results
      showed that its aqueous extract was suitable for MSCs adhesion and proliferation.
      Then the alloy was evaluated for biomedical applications in nonfractured distal
      femora of Sprague Dawley rats for 6 weeks, compared with those of pure-Mg and
      stainless steel groups. All rats survived, and hematological and histological
      evaluation showed no abnormal physiology 6 weeks postimplantation, and
      measurements of serum Mg2+ concentration were within normal levels. X-ray
      scanning, microcomputed tomography, and histological examinations were performed
      to evaluate the degradability and osteogenic potential. The results indicated
      that the degradation rate of alloy was 0.91 mm per year, (range 0.77-1.22 mm),
      and pure-Mg 1.80 mm per year (1.43-2.26 mm). The new bone quantity was 3.18 mm3
      (1.46-4.44 mm3 ) in Mg-Ag-Y alloys group, 1.39 mm3 (0.54-2.32 mm3 ) in pure-Mg
      group, and none in stainless steel group. These promising results suggest
      potential clinical application of Mg-Ag-Y alloys for use as resorbable bone
      fixation implant. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 2059-2069, 2018.

PMID- 29569818
TI  - Within-species patterns challenge our understanding of the leaf economics
      spectrum.
AB  - The utility of plant functional traits for predictive ecology relies on our
      ability to interpret trait variation across multiple taxonomic and ecological
      scales. Using extensive data sets of trait variation within species, across
      species and across communities, we analysed whether and at what scales leaf
      economics spectrum (LES) traits show predicted trait-trait covariation. We found
      that most variation in LES traits is often, but not universally, at high
      taxonomic levels (between families or genera in a family). However, we found that
      trait covariation shows distinct taxonomic scale dependence, with some trait
      correlations showing opposite signs within vs. across species. LES traits
      responded independently to environmental gradients within species, with few
      shared environmental responses across traits or across scales. We conclude that,
      at small taxonomic scales, plasticity may obscure or reverse the broad
      evolutionary linkages between leaf traits, meaning that variation in LES traits
      cannot always be interpreted as differences in resource use strategy.

PMID- 29569819
TI  - Outlier experienced surgeon's performances impact on benchmark for technical
      surgical skills training.
AB  - BACKGROUND: Training in medicine must move to an outcome-based approach. A
      proficiency-based progression outcome approach to training relies on a
      quantitative estimation of experienced operator performance. We aimed to develop
      a method for dealing with atypical expert performances in the quantitative
      definition of surgical proficiency. METHODS: In study one, 100 experienced
      laparoscopic surgeons' performances on virtual reality and box-trainer simulators
      were assessed for two similar laparoscopic tasks. In study two, 15 experienced
      surgeons and 16 trainee colorectal surgeons performed one simulated hand-assisted
      laparoscopic colorectal procedure. Performance scores of experienced surgeons in
      both studies were standardized (i.e. Z-scores) using the mean and standard
      deviations (SDs). Performances >1.96 SDs from the mean were excluded in
      proficiency definitions. RESULTS: In study one, 1-5% of surgeons' performances
      were excluded having performed significantly below their colleagues. Excluded
      surgeons made significantly fewer correct incisions (mean = 7 (SD = 2) versus
      19.42 (SD = 4.6), P < 0.0001) and a greater proportion of incorrect incisions
      (mean = 45.71 (SD = 10.48) versus 5.25 (SD = 6.6), P < 0.0001). In study two, one
      experienced colorectal surgeon performance was >4 SDs for time to complete the
      procedure and >6 SDs for path length. After their exclusions, experienced
      surgeons' performances were significantly better than trainees for path length: P
      = 0.031 and for time: P = 0.002. CONCLUSION: Objectively assessed atypical expert
      performances were few. Z-score standardization identified them and produced a
      more robust quantitative definition of proficiency.

PMID- 29569820
TI  - Can pathological reports of rectal cancer provide national quality indicators?
AB  - BACKGROUND: Rectal cancer care has become increasingly complex and requires
      accurate information. The pathology report is a vital tool for accessing
      information to gauge a patient's prognosis and to guide treatment decisions. The
      aim of this study was to assess the quality of histopathological reporting and
      surgery for rectal cancer in New Zealand using defined quality indicators.
      METHODS: This is a retrospective audit of pathological reports of all resected
      rectal cancer pathology reports submitted to the New Zealand Cancer Registry
      (NZCR) in 2015. The quality of reporting was assessed using specified criteria:
      synoptic report, adequate lymph node retrieval, reporting of circumferential
      resection margin (CRM) and mesorectal excision quality. Surgical outcomes were
      sphincter preservation rate, CRM clearance and complete mesorectal excision.
      RESULTS: A total of 803 patients with rectal cancer were reported to the NZCR in
      2015, 505 underwent proctectomy. A total of 89.5% of reports were structured,
      81.8% reported mesorectal excision quality and 86.7% reported CRM status.
      Adequate lymph node retrieval was obtained in 65.1%, complete mesorectal excision
      in 84.6% and positive CRM in 6.2% of cases. Quality varied between laboratories
      and district health boards. High-volume laboratories had higher quality
      reporting. Surgeon volume and training was related to adequate lymph node
      retrieval but not CRM clearance nor mesorectal excision quality. CONCLUSION: High
      quality pathological reporting is associated with the use of synoptic reporting
      templates. Surgical outcomes for rectal cancer in New Zealand, especially the low
      rate of CRM involvement, compare favourably with international audits.

PMID- 29569821
TI  - Efficacy and possible mechanisms of Botulinum Toxin type A on hypertrophic
      scarring.
AB  - BACKGROUND: Clinical observations indicate that Botulinum toxin type A (BTXA) can
      inhibit the growth and improve the eventual appearance of hypertrophic scarring.
      However, the molecular mechanism remains unclear. OBJECTIVE: We used human keloid
      fibroblasts to investigate the molecular mechanism of BTXA on hypertrophic
      scarring. METHODS: Different concentrations of BTXA (0.01, 0.1, 1, and 10 U/L)
      were used to treat keloid fibroblasts. Changes in cellular morphology, viability,
      proliferation, cell cycle, and apoptosis were observed by immunofluorescence, MTT
      assay, and flow cytometry. In addition, real-time qPCR and Western blotting were
      used to explore the potential molecular mechanisms. RESULTS: Keloid fibroblast
      viability decreased with increasing BTXA dose. After BTXA treatment, the volume
      of keloid fibroblasts cells increased, but the nucleus of cells shrunk. Long thin
      dendrites were formed as the concentration of BTXA increased. Furthermore, the
      proliferation and S phase of keloid fibroblasts were inhibited by BTXA. Matrix
      metalloproteinase (, MMP)-1 and -2 RNA and protein showed high expression, but
      TGF-beta1 and MMP-9 showed low expression than the control. CONCLUSION: Botulinum
      toxin type A may promote the healing of scars by inhibiting the proliferation of
      keloid fibroblasts and regulating the expression of TGF-beta1, which could affect
      the expression of MMP-1 and MMP-2. This study provides theoretical support for
      the clinical application of BTXA to control hypertrophic scarring.

PMID- 29569822
TI  - A systematic review of drug treatment of vulvodynia: evidence of a strong placebo
      effect.
AB  - BACKGROUND: Vulvodynia is the most common type of chronic pelvic pain and
      dyspareunia in premenopausal women. The effect of drugs for the treatment of
      vulvodynia remains poorly discussed. OBJECTIVES: To conduct a systematic review
      of randomised controlled studies which assess medications used to treat vulvar
      pain in vulvodynia. SEARCH STRATEGY: Web of Science, Cochrane Library, EBSCO
      Academic, LILACS and MEDLINE were searched from 1985 to September 2016. SELECTION
      CRITERIA: Randomised controlled trials comparing any kind of medication for
      vulvodynia treatment with placebo or with another medication in adult patients
      were included. DATA COLLECTION AND ANALYSIS: The two investigators independently
      conducted data extraction. The synthesis was provided by the pain reduction
      index. Study quality assessment was performed using the Cochrane Handbook for
      Systematic Reviews of Intervention and analysis of publication bias was
      conducted. MAIN RESULTS: Five studies were included in qualitative synthesis.
      Number of participants varied from 30 to 133 participants among the eligible
      studies, resulting in a total of 297 patients. The pain reduction rates of
      patients with vulvodynia assessed by Q-tipped cotton test and visual analogue
      scale varied between studies. Placebo was shown to be as effective as any
      medication. CONCLUSIONS: There is a need for further studies evaluating topical
      monotherapy for the treatment of vulvodynia, as they are the main drugs used in
      clinical practice. TWEETABLE ABSTRACT: No medication has shown impact on vulvar
      pain in vulvodynia. There is evidence of a placebo effect.

PMID- 29569823
TI  - Plasmonic Hotspots in Air: An Omnidirectional Three-Dimensional Platform for
      Stand-Off In-Air SERS Sensing of Airborne Species.
AB  - Molecular-level airborne sensing is critical for early prevention of disasters,
      diseases, and terrorism. Currently, most 2D surface-enhanced Raman spectroscopy
      (SERS) substrates used for air sensing have only one functional surface and
      exhibit poor SERS-active depth. "Aerosolized plasmonic colloidosomes" (APCs) are
      introduced as airborne plasmonic hotspots for direct in-air SERS measurements.
      APCs function as a macroscale 3D and omnidirectional plasmonic cloud that
      receives laser irradiation and emits signals in all directions. Importantly, it
      brings about an effective plasmonic hotspot in a length scale of approximately
      2.3 cm, which affords 100-fold higher tolerance to laser misalignment along the z
      axis compared with 2D SERS substrates. APCs exhibit an extraordinary
      omnidirectional property and demonstrate consistent SERS performance that is
      independent of the laser and analyte introductory pathway. Furthermore, the first
      in-air SERS detection is demonstrated in stand-off conditions at a distance of
      200 cm, highlighting the applicability of 3D omnidirectional plasmonic clouds for
      remote airborne sensing in threatening or inaccessible areas.

PMID- 29569824
TI  - Determining the optimal time for radical cystectomy after neoadjuvant
      chemotherapy.
AB  - OBJECTIVE: To determine whether the recovery window (RW) between neoadjuvant
      chemotherapy (NAC) and radical cystectomy (RC) affects 90-day postoperative
      morbidity and incidence of lymph node metastasis. PATIENTS AND METHODS: We
      reviewed patients treated with NAC and RC from 1995 to 2013 for <=cT4 N0 M0
      bladder cancer. The association of the RW with 90-day perioperative morbidity and
      lymph node metastasis was determined. Generalised linear models were used to
      determine predictors of each endpoint. Patients were stratified into four RWs by
      21-day intervals (18-42; 43-63; 64-84; and >=85 days) from last day of NAC to RC.
      RESULTS: We evaluated 306 patients with RW information during the study period.
      The median (range) RW was 46 (18-199) days. There was no difference in overall
      morbidity, re-admission, or major complication rates amongst the four RWs. In the
      multivariable analysis extravesical disease was an independent predictor of
      overall morbidity (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.16-3.26;
      P = 0.011). Age (OR 1.05, 95% CI: 1.02-1.09; P = 0.004), and surgical duration
      >=7 h (OR 2.87, 95% CI: 1.52-5.42; P = 0.001) were independent predictors of
      major complications. Only surgical duration >=7 h was a predictor of re-admission
      (OR 2.24; 95% CI: 1.26-3.98; P = 0.006). A RW of >=85 days had the highest
      incidence of node-positive disease (pN+; 40%). In a separate multivariable model
      that included clinical predictors for pN+, a RW of >=85 days was an independent
      predictor of nodal metastasis (OR 2.92, 95% CI: 1.20-7.09; P = 0.018).
      CONCLUSION: Patients treated with NAC for bladder cancer can undergo RC between
      18 and 84 days (2.5-12 weeks) after NAC with no difference in the risk of
      perioperative morbidity. Delaying surgery beyond 12 weeks was associated with a
      significant risk of lymph node metastasis.

PMID- 29569825
TI  - High-efficiency genome editing using a dmc1 promoter-controlled CRISPR/Cas9
      system in maize.
AB  - Previous studies revealed that the promoters for driving both Cas9 and sgRNAs are
      quite important for efficient genome editing by CRISPR/Cas9 in plants. Here, we
      report our results of targeted genome editing using the maize dmc1 gene promoter
      combined with the U3 promoter for Cas9 and sgRNA, respectively. Three loci in the
      maize genome were selected for targeting. The T0 plants regenerated were highly
      efficiently edited at the target sites with homozygous or bi-allelic mutants
      accounting for about 66%. The mutations in T0 plants could be stably transmitted
      to the T1 generation, and new mutations could be generated in gametes or zygotes.
      Whole-genome resequencing indicated that no off-target mutations could be
      detected in the predicted loci with sequence similarity to the targeted site. Our
      results show that the dmc1 promoter-controlled (DPC) CRISPR/Cas9 system is highly
      efficient in maize and provide further evidence that the optimization of the
      promoters used for the CRISPR/Cas9 system is important for enhancing the
      efficiency of targeted genome editing in plants. The evolutionary conservation of
      the dmc1 gene suggests its potential for use in other plant species.

PMID- 29569826
TI  - A Telomerase-Responsive DNA Icosahedron for Precise Delivery of Platinum
      Nanodrugs to Cisplatin-Resistant Cancer.
AB  - A telomerase-responsive DNA icosahedron was designed to precisely release caged
      platinum nanodrugs into cisplatin-resistance tumor cells for effective therapy.
      This DNA icosahedron was constructed from two pyramidal DNA cages connected with
      telomerase primers and telomeric repeats, and platinum nanodrugs were then
      encapsulated into the DNA structure. In the presence of telomerase, the primers
      are extended, leading to inner-chain substitution of the DNA icosahedron and
      subsequent release of the caged nanodrugs. This DNA icosahedron can precisely
      release caged nanodrugs in response to telomerase in tumor cells, giving enhanced
      anticancer efficacy in drug-resistant carcinoma and with reduced toxicity to
      normal tissues. We speculate that this precisely designed, well controlled DNA
      cage could be generalized to diverse anticancer drugs.

PMID- 29569828
TI  - The kinetics and mechanism of bone morphogenetic protein 2 release from calcium
      phosphate-based implant-coatings.
AB  - Biomimetically deposited calcium phosphate-based coatings of prostheses can serve
      as a vehicle for the targeted delivery of growth factors to the local implant
      environment. Based on indirect evidence in previous studies we hypothesize that
      such agents are liberated gradually from the coating via a cell-mediated
      degradation. In the present study, we tested this hypothesis by investigating the
      release mechanism and its kinetics by use of a radiolabeled osteogenic agent (131
      I-BMP-2) under conditions in which native cell populations with a coating
      degradative potential were either absent or present. The release of 131 I-BMP-2
      was monitored for 5 weeks, either in vitro or after implantation at an ectopic
      (subcutaneous) site in rats in vivo. Only from implants that bore a coating
      incorporated depot of bone morphogenetic protein 2 (BMP-2) was the agent released
      slowly and steadily over 5 weeks, that is, 50% of the loaded dose was liberated
      in vivo (5 to 10% weekly), as against 14.6% in vitro (less than 1% weekly). The
      coatings bearing an incorporated depot of BMP-2 underwent significant cell
      mediated degradation, whereas under cell-free conditions no degradation occurred,
      and the spontaneous release of BMP-2 was negligible. Our findings confirm this
      carrier system to be a suitable vehicle for the sustained and cell-mediated
      delivery of BMP-2. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A:2363-2371, 2018.

PMID- 29569829
TI  - Compartment syndrome of the deltoid and pectoralis major in a young man following
      quetiapine use.

PMID- 29569827
TI  - Notch and Aryl Hydrocarbon Receptor Signaling Impact Definitive Hematopoiesis
      from Human Pluripotent Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) stand to revolutionize the way we study
      human development, model disease, and eventually, treat patients. However, these
      cell sources produce progeny that retain embryonic and/or fetal characteristics.
      The failure to mature to definitive, adult-type cells is a major barrier for iPSC
      based disease modeling and drug discovery. To directly address these concerns, we
      have developed a chemically defined, serum and feeder-free-directed
      differentiation platform to generate hematopoietic stem-progenitor cells (HSPCs)
      and resultant adult-type progeny from iPSCs. This system allows for strict
      control of signaling pathways over time through growth factor and/or small
      molecule modulation. Through direct comparison with our previously described
      protocol for the production of primitive wave hematopoietic cells, we demonstrate
      that induced HSPCs are enhanced for erythroid and myeloid colony forming
      potential, and strikingly, resultant erythroid-lineage cells display enhanced
      expression of adult beta globin indicating definitive pathway patterning. Using
      this system, we demonstrate the stage-specific roles of two key signaling
      pathways, Notch and the aryl hydrocarbon receptor (AHR), in the derivation of
      definitive hematopoietic cells. We illustrate the stage-specific necessity of
      Notch signaling in the emergence of hematopoietic progenitors and downstream
      definitive, adult-type erythroblasts. We also show that genetic or small molecule
      inhibition of the AHR results in the increased production of CD34+ CD45+ HSPCs
      while conversely, activation of the same receptor results in a block of
      hematopoietic cell emergence. Results presented here should have broad
      implications for hematopoietic stem cell transplantation and future clinical
      translation of iPSC-derived blood cells. Stem Cells 2018;36:1004-1019.

PMID- 29569830
TI  - The efficacy and complications of a new technique of Abobotulinum-toxin A
      (Dysport) injection in patients with glabellar lines.
AB  - BACKGROUND: Abobotulinum- toxin A is used extensively for the treatment of frown
      (glabellar) lines. AIMS: The aim of this study was to evaluate the efficacy and
      complications of a new injection technique and to assess the amount of
      satisfaction in patients with the frown lines. METHODS: This cross-sectional
      study was conducted in 104 patients with moderate-to-severe glabellar lines. In
      the new technique by reassessing the responsible anatomic muscles of wrinkles, we
      tried to modify the injection technique of Abobotulinum-toxin A to yield more
      favorable results. The range and severity of frown lines were assessed by a 4
      score test and a photograph taken before and 2 weeks after the injection.
      Patients were followed up to 180 days after injection. RESULTS: The response time
      of 87.5% of patients was within the first 48 hours and the remaining 12.5% showed
      the symptoms within the first week after injection. At 30 days after injection,
      the frown lines had disappeared in 88.5% of patients in static mode and 85.6% in
      mechanic mode. Maximum injection durability in the first 3, 4, and 6 months after
      injection was 82%, 52%, and 38%, respectively. The amount of complete
      satisfaction after 3 months was reported to be 86.5%. CONCLUSIONS: This study
      indicated that the new injection technique of Abobotulinum-toxin A could be
      beneficial in the treatment of frown lines with more satisfactory results,
      especially in those patients who were not contented with the present conventional
      method.

PMID- 29569831
TI  - Direct Synthesis of a Covalently Self-Assembled Peptide Nanogel from a Tyrosine
      Rich Peptide Monomer and Its Biomineralized Hybrids.
AB  - There has been significant progress in the self-assembly of biological materials,
      but the one-step covalent peptide self-assembly for well-defined nanostructures
      is still in its infancy. Inspired by the biological functions of tyrosine, a
      covalently assembled fluorescent peptide nanogel is developed by a ruthenium
      mediated, one-step photo-crosslinking of tyrosine-rich short peptides under the
      visible light within 6 minutes. The covalently assembled peptide nanogel is
      stable in various organic solvents and different pH levels, unlike those made
      from vulnerable non-covalent assemblies. The semipermeable peptide nanogel with a
      high density of redox-active tyrosine acts as a novel nano-bioreactor, allowing
      the formation of uniform metal-peptide hybrids by selective biomineralization
      under UV irradiation. As such, this peptide nanogel could be useful in the design
      of novel nanohybrids and peptidosomes possessing functional nanomaterials.

PMID- 29569832
TI  - Bone Marrow-Derived Mesenchymal Stem Cells Protect Islet Grafts Against
      Endoplasmic Reticulum Stress-Induced Apoptosis During the Early Stage After
      Transplantation.
AB  - Early loss of grafted islets is the main obstacle to achieve favorable outcomes
      of islet transplantation. Mesenchymal stem cells are known to have a protective
      effect; however, its mechanism remains unclear. We hypothesized that bone marrow
      derived mesenchymal stem cells (BMSCs) can protect grafted islets against
      endoplasmic reticulum stress (ERS)-induced apoptosis. In syngeneic streptozocin
      induced diabetic BALB/c mice, islet grafts decreased blood glucose levels;
      however, the effect was not fully functional from the immediate post-transplant
      phase. beta-Cell apoptosis was proven on days 1 and 3 after transplantation.
      Ultra-structural evidence of ERS was observed along with increased expressions of
      marker protein BIP and apoptosis-related protein CHOP. In contrast, BMSC co
      transplantation maintained glucose hemostasis, inhibited apoptosis and alleviated
      ERS. In ex vivo culture, BMSCs improved viability of islets and decreased
      apoptosis. Increased ERS were observed in cultured islets exposed to hypoxia, but
      not in the islets cocultured with BMSCs. Furthermore, cocultured BMSCs protected
      islets against ERS-induced apoptosis as well as improved their insulin secretion,
      and BMSCs alleviated ERS by improving Myc expression through both stromal cell
      derived factor 1 signal and contact effect. In conclusion, BMSCs protected the
      grafted islets against ERS-induced apoptosis during the early stage after
      transplantation. This study opens a new arena for ERS-targeted therapy to improve
      outcomes of islet transplantation. Stem Cells 2018;36:1045-1061.

PMID- 29569833
TI  - Exploring the anti-quorum sensing activity of a d-limonene nanoemulsion for
      Escherichia coli O157:H7.
AB  - In this study, a d-limonene nanoemulsion was developed by using a spontaneous
      emulsification method and its potential to inhibit the quorum sensing (QS)
      regulated properties of Escherichia coli O157:H7 (E. coli) were revealed. The
      results in this study showed that d-limonene nanoemulsion inhibited E. coli
      biofilm formation through the suppression of curli and extracellular polymeric
      substance (EPS) production without inhibiting cell growth, and decreased swimming
      and swarming ability. Further analyses showed that d-limonene nanoemulsion
      interfered with auto-inducer 2 (AI-2) communication and repressed the expression
      of curli related genes and AI-2 importer genes in E. coli. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1979-1986, 2018.

PMID- 29569835
TI  - Simultaneous release of melatonin and methylprednisolone from an injectable in
      situ self-crosslinked hydrogel/microparticle system for cartilage tissue
      engineering.
AB  - Recently, injectable hydrogel/microparticle systems have so considered for tissue
      engineering and regenerative medicine. In this study, we produced an injectable
      in situ self-crosslinked hydrogel/microparticle system for simultaneous dual drug
      delivery. First, melatonin conjugated chitosan microparticle loaded with
      methylprednisolone (MCC-MP) microparticle was fabricated by the covalent linkage
      of melatonin to chitosan by N-hydroxysuccinimide (NHS)1-Ethyl-3-(3-dimethylamino
      propyl)-carbodiimide (EDC) followed by an ionic gelation of MCC and MP using
      tripolyphosphate (TPP). Second, the hydrogel was prepared by the connection
      between the aldehyde group of alginate oxide (AD) and the amine group belonging
      to carboxymethyl chitosan (CMC) via Schiff base reaction. Finally, microparticle
      was incorporated into the AD-CMC hydrogel to produce a hydrogel/microparticle
      system. Hydrogel/microparticle was assessed by many techniques including
      microscopy, spectroscopy, particle size measurements, mechanical analysis,
      injectability, rheological analyses to ascertain hydrogel/microparticle
      properties. The biological assays of mesenchymal stem cells (MSCs) culture, 3
      (4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), acridine
      orange/propidium iodide (AO/PI), and 4, 6-diamidino-2-phenylindole (DAPI) to
      assess cell viability and dimethylmethylene blue (DMMB) to evaluate proteoglycan
      content were done. The release profiles of melatonin and MP showed acceptable
      release after 60 and 20 days, respectively. The hydrogel/microparticle system has
      the ability to sustain cells alive. A higher rate of proteoglycan content was
      observed in hydrogel/microparticle as compared with hydrogel. With appropriate
      biocompatibility and adequate properties, this system can be a proper alternative
      for cartilage tissue engineering. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 1932-1940, 2018.

PMID- 29569834
TI  - Knee extension rate of torque development and peak torque: associations with
      lower extremity function.
AB  - BACKGROUND: With aging, the ability to generate muscle force decreases,
      contributing to declines in physical functions such as walking. While most
      studies assess muscle force by peak torque, the rate of torque development (RTD)
      reflects a dynamic component of muscle performance that is important for physical
      function. Using data from the Baltimore Longitudinal Study of Aging, we assessed
      whether RTD adds significantly to peak torque in associations with lower
      extremity performance. If so, RTD may help identify weak older adults for
      screening and intervention. METHODS: We assessed associations of RTD and peak
      torque with physical performance independent of demographics, BMI, body
      composition, and each other in 1089 Baltimore Longitudinal Study of Aging
      participants (49.7% women; aged 26 to 96 years; women, 64.0 +/- 13.8 years; men,
      68.4 +/- 14.4 years). Peak torque was assessed by isometric and 30 deg/s
      isokinetic knee extension tests. Peak RTD was operationalized as the maximum
      torque-time slope among successive 50 ms epochs over the first 3 s of a test of
      knee extension isometric strength, with the knee joint positioned at 120 deg of
      flexion. A battery of lower extremity performance tests included gait speed
      during a 6 m walk at usual and fast pace (6 m usual and fast), time to complete a
      400 m walk at fast pace (400 m), distance covered in a 2.5 min walk at normal
      pace (2.5 min), time to complete 5 and 10 chair stands, and two summary tests of
      lower extremity performance. Sex-stratified generalized linear regression models
      were adjusted for age, race, BMI, appendicular lean mass, and whole body fat
      mass. RESULTS: In men, independent of either measure of peak torque and
      cofactors, RTD was a significant (P < 0.05) predictor of all lower extremity
      performance tests except the 400 m and 2.5 min walks. In women, independent of
      peak torque, RTD was only a significant independent correlate of the 6 m fast
      walk (P < 0.001). CONCLUSIONS: RTD independently contributes to physical
      functions in men but less in women. The mechanisms underlying the sex difference
      are unclear and require further study.

PMID- 29569836
TI  - A comparative study of the effect of submicron porous and smooth ultrafine
      grained Ti-20Mo surfaces on osteoblast responses.
AB  - The surface of an orthopaedic implant plays a crucial role in determining the
      adsorption of proteins and cell functions. A detailed comparative study has been
      made of the in vitro osteoblast responses to coarse-grained (grain size: 500
      MUm), ultrafine-grained (grain size: 100 nm), coarse-porous (pore size: 350 nm),
      and fine-porous (pore size: 155 nm) surfaces of Ti-20Mo alloy. The purpose was to
      provide essential experimental data for future design of orthopaedic titanium
      implants for rapid osseointegration. Systematic original experimental data was
      produced for each type of surfaces in terms of surface wettability, cell
      morphology, adhesion, growth, and differentiation. Microscopic evidence was
      collected to reveal the detailed interplay between each characteristic surface
      with proteins or cells. Various new observations were discussed and compared with
      literature data. It was concluded that the coarse-porous surfaces offered the
      optimum topographical environment for osteoblasts and that the combination of
      ultrafine grains and considerable grain boundary areas is not an effective way to
      enhance cell growth and osteogenic capacity. Moreover, pore features (size and
      depth) have a greater effect than smooth surfaces on cell growth and osteogenic
      capacity. It proves that cells can discern the difference in pore size in the
      range of 100-350 nm. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 2020-2033, 2018.

PMID- 29569837
TI  - Applied Concepts in PBPK Modeling: How to Extend an Open Systems Pharmacology
      Model to the Special Population of Pregnant Women.
AB  - This tutorial presents the workflow of adapting an adult physiologically based
      pharmacokinetic (PBPK) model to the pregnant populations using the Open Systems
      Pharmacology (OSP) software suite (www.open-systems-pharmacology.org). This
      workflow is illustrated using a previously published PBPK model for metronidazole
      that is extrapolated to pregnancy by parameterizing and extending the model
      structure in terms of pregnancy-induced physiological changes. Importantly, this
      workflow can be applied to other scenarios where PBPK models need to be re
      parameterized or structurally modified.

PMID- 29569838
TI  - The feasibility study of an in situ marine polysaccharide-based hydrogel as the
      vitreous substitute.
AB  - Although various biopolymers and synthetic compounds have been proposed and
      tested as the vitreous substitutes, no ideal material has been identified yet. In
      the present study, we developed an in situ-formed hydrogel by crosslinking
      hydroxypropyl chitosan with alginate dialdehyde. Physical properties of the
      hydrogel were studied and the cytotoxicity was evaluated using L929 fibroblasts,
      rabbit corneal endothelial cells and retinal pigment epithelial cells. In a
      preliminary in vivo study, the hydrogel was employed as vitreous substitute after
      vitrectomy surgery on rabbits and multiple parameters indicating biosafety and
      biocompatibility were measured and analyzed postoperatively. Our results showed
      that the refractive index, transmittance, pH value and density of the hydrogel
      were similar to those of human vitreous. Cytotoxicity tests demonstrated the
      hydrogel to be nontoxic to all of the three cell lines selected. Using the rabbit
      model, we showed that the hydrogel could form in situ and postoperative analysis
      of slit-lamp observation, intraocular pressure, corneal endothelium examination,
      B-scan ultrasound and fundus photography showed no significant adverse reactions
      in the operated eyes during the 90-day follow-up. However, electroretinogram and
      histopathological examinations indicated minor vision decline and decrease of the
      densities of cones and rods in the operated rabbit eyes. Collectively, our study
      suggested that the in situ-formed hydrogel could potentially be used as a
      vitreous substitute, with its long-term safety and efficacy to be further
      assessed. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1997
      2006, 2018.

PMID- 29569839
TI  - Soy Phytoestrogens Do Not Fully Reverse Changes in Rat Pituitary Castration
      Cells: Unbiased Stereological Study.
AB  - The aim of the study was to examine the potential of the principal soy
      isoflavones, genistein and daidzein, or isoflavone rich soy extract to recover
      pituitary castration cells in orchidectomized adult male rats in comparison with
      the effects of estradiol. Two weeks post orchidectomy (Orx), animals received
      estradiol-dipropionate, genistein, daidzein or soy extract subcutaneously for 3
      weeks. Control sham-operated (So) and Orx rats received just the vehicle. Changes
      in the volumes of pars distalis, of individual follicle-stimulating hormone (FSH)
      and luteinizing hormone (LH) containing cells, their volume, numerical density
      and number were determined by unbiased design-based stereology. The intracellular
      content of betaFSH and betaLH was estimated by relative intensity of fluorescence
      (RIF). Orchidectomy increased all examined stereological parameters and RIF.
      Compared to Orx, estradiol increased the volume of pars distalis, but reversed
      RIF and all morphometric parameters of gonadotropes to the level of So rats,
      except their number. Treatments with purified isoflavones and soy extract
      decreased RIF to the control So level, expressing an estradiol-like effect.
      However, the histological appearance and morphometrical features of gonadotropes
      did not follow this pattern. Genistein increased the volume of pars distalis,
      decreased the volume density of LH-labeled cells and raised the number of
      gonadotropes. Daidzein decreased the cell volume of gonadotropic cells but
      increased their number and numerical density. Soy extract induced an increase in
      number and numerical density of FSH-containing cells. Therefore, it can be
      concluded that soy phytoestrogens do not fully reverse the Orx-induced changes in
      pituitary castration cells. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29569840
TI  - Traumatic dental injuries-Prevalence and severity among 16-year-old pupils in
      western Norway.
AB  - BACKGROUND/AIMS: Published data on prevalence and severity of traumatic dental
      injuries (TDI) in Norway are limited. The aims of this study were to assess
      prevalence, distribution and severity of TDI in the permanent dentition of 16
      year-old pupils in western Norway. MATERIAL AND METHODS: A retrospective
      longitudinal study, including historical clinical data, was conducted among 16
      year-old high school pupils in the County of Hordaland, western Norway. First
      grade pupils attending high school, born in 1997, were invited to participate (n
      = 5184). Consent was given to access their dental records in the Public Dental
      Health Service in Hordaland, where information regarding TDI (diagnosis and
      treatment) and radiographs was interpreted. Only TDIs to anterior teeth were
      recorded (canine to canine in the maxilla and mandible) and classified using a
      modified version of the WHO's classification. RESULTS: A total of 2055
      participants were included (response rate 40%). TDI prevalence was 16.4% (338
      pupils), with the maxillary central incisors most affected (64.7%). A total of
      637 teeth were involved. Boys were more prone to injury than girls (P < 0.05).
      Severity of TDI was divided into 3 groups (mild, moderate and severe), with the
      following distribution: 563 mild (88.4%), 39 moderate (6.1%) and 35 severe
      (5.5%). Peak age for TDI was 8-10 years (50.9%). CONCLUSIONS: Prevalence of TDI
      among Norwegian adolescents was moderate. Milder injuries were more frequent than
      moderate and severe injuries. Age and gender were risk factors with regard to
      TDI. Seasonal influence on the occurrence of TDI was not statistically
      significant.

PMID- 29569841
TI  - Many Flavors of Model-Based Meta-Analysis: Part II - Modeling Summary Level
      Longitudinal Responses.
AB  - Meta-analyses typically assess comparative treatment response for an end point at
      specific timepoints across studies. However, during drug development, it is often
      of interest to understand the response time-course of competitor compounds for a
      variety of purposes. Examples of such application include informing study design
      and characterizing the onset, maintenance, and offset of action. This tutorial
      acts as a "points for consideration" document, reviews relevant literature, and
      fits a longitudinal model to an example dataset.

PMID- 29569842
TI  - Incidence and outcomes of out-of-hospital cardiac arrest: A New Zealand
      perspective.
AB  - OBJECTIVE: To describe the incidence and outcomes from out-of-hospital cardiac
      arrest (OHCA) in the New Zealand population served by the St John Ambulance
      Service. METHODS: A retrospective observational study was conducted using data
      from the St John New Zealand OHCA registry, which serves a population of around 4
      million. The incidence and outcomes of adult patients who were treated for an
      OHCA between 1 October 2013 and 30 September 2015 are reported. RESULTS: A total
      of 7996 adult OHCA cases were attended, resuscitation was attempted in 3862 cases
      (60 per 100 000 person-years). The median response time was 9 min (interquartile
      range 7-12), the median age was 66 (interquartile range 53-77) and 69% were men.
      Most events occurred in the home (67%), bystanders witnessed 53%, EMS witnessed
      16% and 31% were unwitnessed. Bystander CPR was administered in 62% of cases and
      8% were defibrillated prior to EMS arrival. Most events had a presumed cardiac
      aetiology (77%) and 38% presented in a shockable rhythm. Of those who had
      attempted resuscitation, a return of spontaneous circulation sustained to
      hospital handover occurred in 30% of events and 15% survived to 30 days. Adjusted
      survival outcomes demonstrated differences according to ethnicity. CONCLUSION:
      This is the first study to describe the epidemiology and outcomes of OHCA in New
      Zealand. Our findings provide important baseline data to monitor temporal trends,
      investigate the impact of changes in the management of OHCA and demonstrate that
      there are opportunities for improvement across the system of care.

PMID- 29569843
TI  - Evaluation of the potential exposure of butterflies to genetically modified maize
      pollen in protected areas in Italy.
AB  - Environmental impacts of genetically modified crops are mandatorily assessed
      during their premarket phase. One of the areas of concern is the possible impact
      on nontarget organisms. Crops expressing Cry toxins might affect Lepidoptera
      larvae living outside cultivated fields, through pollen deposition on wild
      plants, which constitute their food source. While pollen toxicity varies among
      different events, possible exposure of nontarget species depends on the agro
      environmental conditions. This study was conducted in two protected areas in
      Italy, characterized by different climatic conditions, where many Lepidoptera
      species thrive in proximity to maize cultivations. To estimate the possible
      exposure in absence of the actual stressor (e.g., Cry1-expressing maize plants),
      we conducted a two-year field survey of butterflies and weeds. Indicator species
      were selected-Aglais (Inachis) io in the Northern site and Vanessa cardui in the
      Southern site-and their phenology was investigated. Pollen dispersal from maize
      fields was measured by collection in Petri dishes. Duration and frequency of
      exposure was defined by the overlap between pollen emission and presence of
      larvae on host plants. Different risk scenarios are expected in the two regions:
      highest exposure is foreseen for A. io in the Northern site, while minimal
      exposure is estimated for V. cardui in the Southern site. In the latter case,
      locally grown maize cultivars flower in mid-summer in coincidence with an
      aestivation period for several butterfly species due to hot and dry conditions.
      Moreover, host plants of V. cardui are at the end of their life cycle thus
      limiting food availability.

PMID- 29569844
TI  - Why do 'fast track' patients stay more than four hours in the emergency
      department? An investigation of factors that predict length of stay.
AB  - OBJECTIVE: Low-acuity 'fast track' patients represent a large portion of
      Australian EDs' workload and must be managed efficiently to meet the National
      Emergency Access Target. The current study determined the relative importance and
      estimated marginal effects of patient and system-related variables in predicting
      ED fast track patients who stayed longer than 4 h in the ED. METHODS: Data for ED
      presentations between 1 July 2014 and 30 June 2015 were collected from a large
      regional Australian public hospital. Only 'fast track' patients were included in
      the analysis. A gradient boosting machine was used to predict which patients
      would have an ED length of stay greater or less than 4 h. The performance of the
      final model was tested using a validation data set that was withheld from the
      initial analysis. A total of 27 variables were analysed. RESULTS: The model's
      performance was very good (area under receiver operating characteristic curve
      0.89, where 1.0 is perfect prediction). The five most important variables for
      predicting length of stay were time-dependent and system-related (not patient
      related); these were the amount of time taken from when the patient arrived at
      the ED to: (i) order imaging; (ii) order pathology; (iii) request admission to
      hospital; (iv) allocate a clinician to care for the patient; and (v) handover a
      patient between ED clinicians. CONCLUSIONS: We identified the most important
      variables for predicting length of stay greater than 4 h for fast track patients
      in our ED. Identifying factors that influence length of stay is a necessary step
      towards understanding ED patient flow and identifying improvement opportunities.

PMID- 29569845
TI  - In this April issue.

PMID- 29569846
TI  - Sepsis in the older person: The ravages of time and bacteria.

PMID- 29569847
TI  - Review article: Sepsis in the emergency department - Part 3: Treatment.
AB  - Although comprehensive guidelines for treatment of sepsis exist, current research
      continues to refine and revise several aspects of management. Imperatives for
      rapid administration of broad-spectrum antibiotics for all patients with sepsis
      may not be supported by contemporary data. Many patients may be better served by
      a more judicious approach allowing consideration of investigation results and
      evidence-based guidelines. Conventional fluid therapy has been challenged with
      early evidence supporting balanced, restricted fluid and early vasopressor use.
      Albumin, vasopressin and hydrocortisone have each been shown to support blood
      pressure and reduce catecholamine requirements but without effect on mortality,
      and as such should be considered for ED patients with septic shock on a case-by
      case basis. Measurement of quality care in sepsis should incorporate quality of
      blood cultures and guideline-appropriateness of antibiotics, as well as
      timeliness of therapy. Local audit is an essential and effective means to improve
      practice. Multicentre consolidation of data through agreed minimum sepsis data
      sets would provide baseline quality data, required for the design and evaluation
      of interventions.

PMID- 29569849
TI  - Long-Range Corrected DFT Calculations of First Hyperpolarizabilities and
      Excitation Energies of Metal Alkynyl Complexes.
AB  - The performance of the CAM-B3LYP, omegaB97X and LC-BLYP long-range corrected
      density functional theory methods in the calculation of molecular first
      hyperpolarizabilities (beta) and low-lying charge transfer (CT) excitation
      energies of the metal alkynyl complexes M(C=C-4-C6 H4 -1-NO2 )(kappa2 -dppe)(eta5
      -C5 H5 ) [M=Fe (1), Ru (2), Os (3)] and trans-[Ru{C=C-(1,4-C6 H4 C=C)n -4-C6 H4 
      1-NO2 }Cl(kappa2 -dppm)2 ] [n=0 (4), 1 (5), 2 (6)] was assessed. The BLYP, B3LYP
      and PBE0 standard exchange-correlation functionals and the Hartree-Fock method
      were also examined. The BLYP functional was shown to perform poorly in the
      calculation of beta and low-energy CT transitions. The hybrid functionals (B3LYP
      and PBE0) showed significant improvement over the pure functional BLYP, but
      overestimated the hyperpolarizability ratios and the wavelengths of the lowest
      energy metal-to-ligand CT transitions for 5 and 6. The effect of long-range
      corrections is noteworthy, particularly for the larger complexes, improving the
      calculation of beta ratios for 4-6. However, CAM-B3LYP, omegaB97X, and LC-BLYP
      considerably overestimated the low-lying CT energies. PBE0 was found to give the
      best transition energy match for 4. The influence of the phenylene ring
      orientation in the alkynyl ligand on the calculated properties is substantial,
      particularly for the larger complexes. For these types of calculations, a basis
      set with diffuse functions (at least 6-31+G(d)) for the heavy elements is
      recommended.

PMID- 29569851
TI  - Steric Hindrance in Sulfur Vacancy of Monolayer MoS2 Boosts Electrochemical
      Reduction of Carbon Monoxide to Methane.
AB  - The efficient generation of methane by total electroreduction of carbon monoxide
      (CO) could be of benefit for a more sustainable society. However, a highly
      efficient and selective catalyst for this process remains to be developed. In
      this study, density functional theory calculations indicate that steric hindrance
      in monolayer molybdenum sulfide with 2 S vacancies (DV-MoS2 ) can facilitate the
      conversion of CO into CH4 with high activity and selectivity under
      electrochemical reduction at a low potential of -0.53 V vs. RHE and ambient
      conditions. The potential is a significant improvement on the state-of-the-art Cu
      electrode (-0.74 V vs. RHE), with less electrical energy. Moreover, the results
      suggest that such steric hindrance effects are important for structure-sensitive
      catalytic reactions.

PMID- 29569850
TI  - Modeling of the Weight Status and Risk of Nonalcoholic Fatty Liver Disease in
      Elderly Individuals: The Potential Impact of the Disulfide Bond-Forming
      Oxidoreductase A-Like Protein (DsbA-L) Polymorphism on the Weight Status.
AB  - Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity.
      Disulfide bond-forming oxidoreductase A-like protein (DsbA-L) is known to be a
      key molecule in protection against obesity and obesity-induced inflammation. In
      the present study, we used a modeling and simulation approach in an attempt to
      develop body mass index (BMI) and BMI-based NAFLD prediction models incorporating
      the DsbA-L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A
      nonlinear mixed-effect model best represented the sigmoidal relationship between
      the BMI and the logit function of the probability of NAFLD prevalence. The final
      models for BMI and NAFLD showed that DsbA-L rs1917760 polymorphism, age, and
      gender were associated with the BMI, whereas gender, patatin-like phospholipase 3
      rs738409 polymorphism, HbA1c, and high-density and low-density lipoprotein
      cholesterol levels were associated with the risk of NAFLD. This information may
      aid in the genetic-based prevention of obesity and NAFLD in the general elderly
      population.

PMID- 29569852
TI  - Editorial: Toward Personalized Treatment for Systemic Juvenile Idiopathic
      Arthritis.

PMID- 29569853
TI  - Revealing Factors Influencing the Fluorine-Centered Non-Covalent Interactions in
      Some Fluorine-Substituted Molecular Complexes: Insights from First-Principles
      Studies.
AB  - We examine the equilibrium structure and properties of six fully or partially
      fluorinated hydrocarbons and several of their binary complexes using
      computational methods. In the monomers, the electrostatic surface of the fluorine
      is predicted to be either entirely negative or weakly positive. However, its
      lateral sites are always negative. This enables the fluorine to display an
      anisotropic distribution of charge density on its electrostatic surface. While
      this is the electrostatic surface scenario of the fluorine atom, its negative
      sites in some of these monomers are shown to have the potential to engage in
      attractive engagements with the negative site(s) on the same atom in another
      molecule of the same type, or a molecule of a different type, to form bimolecular
      complexes. This is revealed by analyzing the results of current state-of-the-art
      computational approaches such as DFT, together with those obtained from the
      quantum theory of atoms in molecules, molecular electrostatic surface potential
      and symmetry adapted perturbation theories. We demonstrate that the
      intermolecular interaction energy arising in part from the universal London
      dispersion, which has been underappreciated for decades, is an essential factor
      in explaining the attraction between the negative sites, although energy arising
      from polarization strengthens the extent of the intermolecular interactions in
      these complexes.

PMID- 29569854
TI  - Interleukin-25 Axis Is Involved in the Pathogenesis of Human Primary and
      Experimental Murine Sjogren's Syndrome.
AB  - OBJECTIVE: To investigate the role of the interleukin-25 (IL-25)/IL-17 receptor B
      (IL-17RB) axis in experimental Sjogren's syndrome (SS) and in patients with
      primary SS and primary SS-associated lymphoma. METHODS: Expression of IL-25, IL
      17RB, IL-17B, and tumor necrosis factor receptor-associated factor 6 (TRAF6) was
      analyzed on minor salivary gland (SG) samples from patients with primary SS and
      on parotid gland samples from patients with primary SS-associated B cell non
      Hodgkin's lymphoma (NHL). IL-17RB expression and the frequencies of natural group
      2 innate lymphoid cells (ILC2s), inflammatory ILC2s, and M2-polarized macrophages
      were assessed by flow cytometry in SG mononuclear cells and peripheral blood
      mononuclear cells (PBMCs). Tissue distribution of ILC2s was studied by confocal
      microscopy. The role of recombinant IL-25 and of rituximab in modulating IL-25
      expression was investigated in in vitro studies. IL-25/IL-17RB and TRAF6
      expression and the role of IL-25 inhibition were also studied in the experimental
      murine model of SS. RESULTS: Activation of the IL-25/IL-17RB/TRAF6 axis
      correlated with the focus score and was observed in patients with primary SS and
      in patients with primary SS-associated NHL. A significant increase in the
      frequency of inflammatory ILC2s was observed both in SG mononuclear cells and in
      PBMCs. IL-25 stimulation of isolated SG mononuclear cells and PBMCs from patients
      and controls resulted both in inflammatory ILC2 expansion and in increased
      autoantibody production. Rituximab modulated expression of inflammatory ILC2s and
      IL-25 in primary SS. SG protein-immunized mice developed overt SS symptoms with
      increased IL-25 expression and increased frequency of CD4+IL-17RB+TRAF6+ cells.
      IL-25 neutralization attenuated disease progression and tissue pathology in mice
      with experimental SS. CONCLUSION: IL-25 may promote the inflammatory state in
      primary SS and may be a potential target for novel disease-modifying therapeutic
      strategies in patients with primary SS.

PMID- 29569855
TI  - Reply.

PMID- 29569856
TI  - Familial Mediterranean Fever: New Insights Into Cancer Immunoprevention? Comment
      on the Article by Brenner et al.

PMID- 29569857
TI  - Correlation of High-Density Lipoprotein-Associated Paraoxonase 1 Activity With
      Systemic Inflammation, Disease Activity, and Cardiovascular Risk Factors in
      Psoriatic Disease.
AB  - OBJECTIVE: To compare the activity of high-density lipoprotein (HDL)-associated
      paraoxonase 1 (PON1) in patients with psoriasis (PsO) and patients with psoriatic
      arthritis (PsA), and to evaluate the association of PON1 activity with the extent
      of disease activity and severity of the cardiovascular disease (CVD) burden in
      these patients. METHODS: Serum levels of paraoxonase and arylesterase activity
      (both measures of PON1 function in humans) were measured in patients with PsA (n
      = 198, 51.0% male) and patients with PsO (n = 145, 50.3% male) who were enrolled
      in a longitudinal psoriatic disease biorepository. Data on PsA disease activity
      (using the Disease Activity Score in 28 joints [DAS28], Clinical Disease Activity
      Index, and painful/swollen joint counts), preexistent CVD and CVD risk factors
      (including diabetes, dyslipidemia, hypertension, and smoking), Framingham Risk
      Scores for CVD, quality of life measures, and laboratory test findings
      (erythrocyte sedimentation rate, C-reactive protein level, and lipid profiles)
      were recorded. RESULTS: Serum arylesterase activities were significantly lower in
      patients with PsO and patients with PsA (mean +/- SD 111.1 +/- 25.5
      MUmoles/minute/ml and 124.4 +/- 33.4 MUmoles/minute/ml, respectively) compared to
      healthy controls (144.3 +/- 33.4 MUmoles/minute/ml) (each P < 0.001 versus
      healthy controls). Serum arylesterase activity decreased in parallel with
      increasing levels of disease activity (DAS28 scores, P = 0.012), older age (P =
      0.013), higher body mass index (P = 0.042), greater incidence of metabolic
      syndrome (P = 0.004) and hypertension (P = 0.014), and worsening Framingham Risk
      Scores (P = 0.001). However, no correlation was seen between serum arylesterase
      activity and the extent of disease activity or CVD burden in patients with PsO.
      Serum paraoxonase activity trended lower both in patients with PsO and in
      patients with PsA (each P = 0.073 versus healthy controls). However, no
      association was seen between serum paraoxonase activity and the extent of disease
      activity or CVD burden in either of the patient cohorts. CONCLUSION: PON1
      activity is decreased in psoriatic diseases. In the PsA cohort, decreases in
      arylesterase activity correlated with increasing severity of joint disease and
      CVD burden. Arylesterase activity, as compared to paraoxonase activity, appeared
      to serve as a more sensitive predictor of preexisting CV risk factors in the PsA
      cohort. However, this correlation was not observed in the PsO population.

PMID- 29569859
TI  - Exacerbation of Murine Experimental Autoimmune Myositis by Toll-Like Receptor
      7/8.
AB  - OBJECTIVE: Toll-like receptor 7 (TLR-7), TLR-8, and interferon (IFN)-induced
      genes are expressed in patients with idiopathic inflammatory myositis. This study
      was undertaken to investigate whether their activation influences the natural
      history of the disease. METHODS: Experimental autoimmune myositis was induced in
      mice by injection of the amino-terminal portion of the murine histidyl-transfer
      RNA synthetase (HisRS). Disease was compared in the presence or the absence of
      the TLR-7/8 agonist R-848 in wild-type mice and in mice that fail to express the
      IFNalpha/beta receptor (IFNalpha/betaR-null mice). RESULTS: Experimental
      autoimmune myositis induced by a single intramuscular immunization with HisRS
      spontaneously abated after 7-8 weeks. In contrast, levels of anti-HisRS
      autoantibodies, endomysial/perimysial leukocyte infiltration, and myofiber
      regeneration persisted at the end of the follow-up period (22 weeks after
      immunization) in mice immunized with HisRS in the presence of R-848. Myofiber
      major histocompatibility complex (MHC) class I molecules were detectable only in
      mice immunized with both HisRS and R-848. MHC up-regulation occurred early and in
      muscles that were not directly injected with HisRS. Muscle MHC expression
      paralleled with leukocyte infiltration. MHC class I molecules were selectively up
      regulated in myotubes challenged with R-848 in vitro. Type I IFN was necessary
      for the prolonged autoantibody response and for the spreading of the autoimmune
      response, as demonstrated using IFNalpha/betaR-null mice. Muscle infiltration was
      maintained in the injected muscle up to the end of the follow-up period.
      CONCLUSION: TLR-7/8 activation is necessary to induce and maintain a systemic
      autoimmune response targeting the skeletal muscle. This experimental autoimmune
      myositis model reproduces many characteristics of human idiopathic inflammatory
      myopathies and may represent a tool for preclinical studies.

PMID- 29569858
TI  - An Autoimmune Basis for Raynaud's Phenomenon: Murine Model and Human Disease.
AB  - OBJECTIVE: Raynaud's phenomenon (RP) is common in anti-RNP-positive patients with
      rheumatic diseases but is not itself known to be caused by autoimmunity. The aim
      of this study was to assess autoantibodies that could mediate this process.
      METHODS: Antibodies derived from patient sera and from murine models of anti-RNP
      autoimmunity were screened for the ability to induce RP-like tissue ischemia and
      endothelial cell apoptosis in murine models and in vitro systems. RESULTS: RNP
      positive sera from RP patients and murine sera from RNP-positive B cell adoptive
      transfer recipients induced RP-like tissue ischemia and endothelial cell
      apoptosis. Proteomic analysis identified cytokeratin 10 (K10) as a candidate
      autoantigen in RP. Monoclonal anti-K10 antibodies reproduced patterns of ischemic
      tissue loss and endothelial cell apoptosis; K10 knockout or depletion of anti-K10
      activity in serum was protective. Cold exposure enhanced K10 expression and in
      vivo tissue loss. CONCLUSION: Anti-K10 antibodies are sufficient to mediate RP
      like ischemia in murine models and are implicated in the pathogenesis of RP in
      patients with anti-RNP autoimmunity.

PMID- 29569861
TI  - Nutritional strategies to reduce falls risk in older people.
AB  - A literature review found an association between increased falls risk and
      malnutrition, sarcopenia, vitamin D deficiency and dehydration. Strategies to
      identify, prevent and treat these conditions can help to reduce falls risk in at
      risk groups such as frail, older people. Nurses can reduce falls risk in older
      people by raising awareness of risk factors and embedding nutritional strategies
      in local falls reduction strategies.

PMID- 29569860
TI  - Maternal factors and preoperative nutrition in children with mild cases of
      congenital heart disease.
AB  - AIM: The preoperative poor nutrition of children with congenital heart disease
      (CHD) impacts the postoperative rehabilitation process of pediatric CHD cases.
      The factors of these children's preoperative poor nutrition, excluding the
      disease, have been underreported. The aim was to investigate the preoperative
      nutritional status of children with CHD who required a simple surgical repair and
      to analyze the maternal characteristics that are associated with poor nutrition
      in these sick children. METHODS: This was a cross-sectional survey. The weight
      and height of the children were measured, maternal data were collected via a
      questionnaire and a univariate analysis and multivariate logistic regression were
      used to analyze the association between maternal factors and the preoperative
      poor nutrition of the children with CHD. RESULTS: A total of 119 children with
      simple CHD were recruited to the study. The prevalence of poor nutrition was
      higher in the children with CHD ("cases") than in the healthy children
      ("controls"). An increased risk of poor nutrition was associated with lower
      mothers' perception, education level, understanding of the disease, and higher
      anxiety. CONCLUSIONS: Paying attention to maternal anxiety, depression, and
      knowledge and providing interventions for the mothers of children with CHD are
      important in order to promote the nutritional status of these children.

PMID- 29569862
TI  - Recognising and managing age-related dermatoporosis and skin tears.
AB  - Dermatoporosis is a chronic skin fragility syndrome, caused by age and
      environmental factors. People with dermatoporosis have skin whose protective
      mechanical function is reduced and which has a decreased tolerance for friction
      and shearing forces. Skin tears are another clinical consequence of age
      associated skin vulnerability and people with dermatoporosis are at increased
      risk of skin tears. Dermatoporosis may also delay the healing of skin tears,
      making it vital that healthcare professionals are aware of this condition. Skin
      tears have profound effects on the health and well-being of older people, and
      these kinds of injuries are being seen more frequently in clinical practice as
      the average age of the population increases. The treatment of skin tears in three
      older people with dermatoporosis is discussed and the clinical decisions made in
      each case.

PMID- 29569863
TI  - Infection prevention and control challenges of using a therapeutic robot.
AB  - This work was part of a National Institute for Health Research participatory
      action research and practice development study, which focused on the use of a
      therapeutic, robotic baby seal (PARO, for personal assistive robot) in everyday
      practice in a single-site dementia unit in Sussex. From the beginning of January
      2017 until the end of September 2017, the cleaning and cleanliness of PARO was
      monitored through a service audit process that focused on the cleaning, amount of
      use and testing of contamination of PARO being used in everyday clinical practice
      with individuals and in group sessions. Its use and cleaning followed protocols
      developed by the study team, which incorporated hand hygiene and standard
      precaution policies. Its cleanliness was determined using an adenosine
      triphosphate (ATP) luminometer, with a benchmark of 50 relative light units
      (RLU). A reading of ATP below 50RLU is the level of cleanliness recommended for
      social areas in hospital settings. Throughout the study period, monitoring showed
      that all swab zones on PARO were within the benchmark of the 50RLU threshold for
      cleanliness. PARO has an emerging evidence base as a useful therapeutic device.
      However, introducing such devices into clinical practice may encounter barriers
      or concerns from an infection prevention and control (IPC) perspective. This
      study of PARO in clinical practice aims to address the IPC concerns raised and
      offers cleaning and testing protocols and results.

PMID- 29569864
TI  - Correction: Shi et al., Shank Proteins Differentially Regulate Synaptic
      Transmission (eNeuro November/December 2017, 4(6) 0163-15.2017 1-12
      https://doi.org/10.1523/ENEURO.0163-15.2017).
AB  - [This corrects the article DOI: 10.1523/ENEURO.0163-15.2017.][This corrects the
      article DOI: 10.1523/ENEURO.0163-15.2017.].

PMID- 29569865
TI  - Correction: Yaple et al., Transcranial Alternating Current Stimulation Modulates
      Risky Decision Making in a Frequency-Controlled Experiment (eNeuro
      November/December 2017, 4(6) e0136-17.2017 1-10
      https://doi.org/10.1523/ENEURO.0136-17.2017).
AB  - [This corrects the article DOI: 10.1523/ENEURO.0136-17.2017.][This corrects the
      article DOI: 10.1523/ENEURO.0136-17.2017.].

PMID- 29569866
TI  - Single-nucleotide polymorphism (rs11204981) in filaggrin gene and its functional
      significance for asthma among children with eczema.
AB  - The aim of this study was to determine whether SNP in filaggrin gene and
      expression of filaggrin mRNAin buccal epithelium are associated with childhood
      eczema and with the phenotype of childhood eczemacombined with asthma. Genotyping
      for FLG (rs11204981) was performed in the following populations:patients with
      asthma (n = 99); ages 5-18 years (8 +/- 2.1), and control group (n = 98); ages 5
      18 years(12 +/- 2.1) by using Real-time PCR. Level of mRNA expression was
      estimated by using reverse transcriptionand following real-time PCR. It was found
      out that 5.05 % of patients and 2.02 % of control group hadminor allele (AA;
      P>0.05), 27.27 % and 36.36 % of patients and control group, respectively, had
      heterozygousallele (GA; P>0.05) and 67.68 % and 61.62 % had major allele (GG)
      (P>0.05). Variants with theAA-genotype of the FLG rs11204981 were found to be 2.5
      times more frequently among patients than incontrol group. We also found out that
      the level of mRNA FLG expression in GG-genotype is 22.8 +/- 11.67(P>0.05 compared
      to AA-genotype), 92.95 +/- 35.3 in GA genotype (P<0.05compared to GG-genotype)
      and21.8 +/- 13.4 in AA genotype (P>0.05 compared to GA-genotype). Thus,
      heterozygous variant has significantlyhigher expression of filaggrin in buccal
      epithelium. We suggest that SNP in FLG (rs11204981) may serveas an important
      predictive marker for the combined eczema plus asthma phenotype, and that the
      highestlevel of expression in heterozygous may have a protective role in
      developing allergy phenotype.Key words: snp; filaggrin; asthma; paediatrics.

PMID- 29569867
TI  - NITRIC OXIDE SYNTHASE ACTIVITY AND ITS CONCENTRATION IN THE TISSUES OF HUMAN
      THYROID CARCINOMAS.
AB  - The study of the activity of the constitutive form of nitricoxide synthase (cNOS)
      revealed that in the papillary thyroidcarcinomas it corresponded to that detected
      in unchangedextratumoral tissue, while the enzyme activity in follicularcarcinoma
      was half lesser. At the same time, the activity ofinducible nitric oxide synthase
      (iNOS) was higher in thepapillary and follicular carcinomas. Such changes in
      theenzyme activity were associated with an increase in its levelin papillary
      carcinomas, and with minor changes in follicularcarcinomas. In medullary
      carcinomas the parameters understudy corresponded to those in unchanged tissue,
      and in thepapillary carcinoma metastases without changes in enzymeactivity of
      nitric oxide formation, the level of the latter wasmuch higher. Elevated levels
      of nitric oxide and iNOS activityin papillary thyroid carcinomas did not depend
      significantlyon the aggression characteristics of the latter, being howeverabsent
      in tumors of T4 category on a background of reducedcNOS activity and less
      expressed in tumors surrounded by thetissue in the presence of a chronic
      thyroiditis. Furthermore,in the papillary carcinomas of papillary or follicular
      structurenitric oxide level did not differ from the normal range, beingslightly
      higher in tumors of solid or heterogeneous structurewith presence of solid areas,
      whereas in carcinomas ofpapillary-follicular structure it was twice, and in
      tissue of solidinsularstructure three times higher. iNOS hyperactivity
      wasobserved in the carcinomas of different structure, except fortumors of solid
      structure, in the tumor of which enzyme activitywas within the normal range, and
      in tumor of solid-insularstructure where it was significantly higher (as well as
      cNOSactivity) compared with tumors of other structure. Nitric oxidegenerating
      system is involved in the transformation of thyroidcells and progression of tumor
      growth, including throughapoptosis regulation, as shown by the results of an
      analysisof data obtained both in the present study and previously. Thenature of
      such involvement in papillary thyroid carcinomaswith different histological
      structure is different.Key words: nitric oxide; constitutive and inducible nitric
      oxidesynthase; thyroid carcinoma; apoptosis.

PMID- 29569868
TI  - What happens to an acellular dermal matrix after implantation in the human body?
      A histological and electron microscopic study.
AB  - Acellular matrices are used for various purposes and they have been studied
      extensively for their potential roles in regenerating tissues or organs. The
      acellular matrix generates physiological cues that mimic the native tissue
      microenvironment. Acellular dermal matrix (ADM) is a soft connective tissue graft
      generated by a decellularization process that preserves the intact extracellular
      skin matrix. Upon implantation, this structure serves as a scaffold for donor
      side cells to facilitate subsequent incorporation and revascularization. In
      breast reconstruction, ADM is used mainly for lower pole coverage and the shaping
      of a new breast. It helps control the positioning of the implant in the
      inframammary fold, and prevent the formation of contractile pseudocapsule around
      the breast implant. In this study, we provide a comprehensive histological
      description of ADM used for human breast reconstruction over the course of
      several months following implementation. Using immunohistochemical methods (a
      panel of 12 antibodies) coupled with optical and transmission electron
      microscopy, we confirmed that the original acellular dermal matrix became
      recolonized by fibroblasts and myofibroblasts, and also by various other free
      cells of the connective tissue (lymphocytes, macrophages and multinucleated giant
      cells, granulocytes, mast cells) after implantation into the patient's body.
      Within the implanted ADM, there was a relatively rapid ingrowth of blood vessels.
      Lymphatic vessels were only detected in one case 9 months after the implantation
      of the ADM. These results suggest that lymphangiogenesis is a longer process than
      angiogenesis.

PMID- 29569869
TI  - Leptin affects filopodia and cofilin in NK-92 cells in a dose- and time-dependent
      manner.
AB  - Hyperleptinemia, associated with obesity, is related with immune dysfunction and
      carcinogenesis. Natural Killer (NK) cells, a major component of the innate immune
      system are mediators of anti-tumor immunity and the most actively migrating cells
      among leukocytes. Actin rearrangement, promoted by cofilin plays a central role
      in cellular migration. Leptin affects the phosphorylation-dependent activity of
      cofilin and thus actin remodeling. We used human NK-92 cells to explore the in
      vitro effects of leptin on co-localization of cofilin and F-actin and on
      morphological changes in NK cells. NK-92 cells were incubated with different
      leptin concentrations (10 and 100 ng/mL) for 30 min and 24 h and
      immunocytochemically stained. Results demonstrate a dose- and time-dependent
      influence of leptin on cellular morphology. Utilizing confocal microscopy, we
      observed that the co-localization of cofilin-1 and F-actin was slightly
      influenced by leptin. In summary, the present study demonstrates an impact of a
      physiological leptin stimulation on the filopodia length, and a time-dependent
      effect on the co-localization of cofilin and F-actin in NK-92 cells.

PMID- 29569870
TI  - Novel insights into pericarp, protein body globoids of aleurone layer, starchy
      granules of three cereals gained using atomic force microscopy and environmental
      scanning electronic microscopy.
AB  - In this study, we applied Environmental Scanning Electron Microscopy-Energy
      Dispersive Spectroscopy (ESEM-EDS) and Atomic Force Microscopy (AFM) analysis to
      three different cereal caryopses: barley, oat and einkorn wheat. The
      morphological structures, chemical elemental composition and surface
      characteristics of the three cereals were described. Regarding the morphology,
      barley showed the thickest pericarp, providing a strong barrier digestion and
      absorption of nutrients. The aleurone layer of each cereal type contained protein
      body globoids within its cells. Large type-A and small type-B starchy granules
      were revealed in the endosperm of barley and einkorn wheat, whereas irregular
      starchy granules were found in oats. The starchy granule elemental composition,
      detected by ESEM-EDS, was rather homogenous in the three cereals, whereas the
      pericarp and protein body globoids showed heterogeneity. In the protein body
      globoids, oats showed higher P and K concentrations than barley and einkorn
      wheat. Regarding the topographic profiles, detected by AFM, einkorn wheat starchy
      granules showed a surface profile that differed significantly from that of oats
      and barley, which were quite similar to one another. The present work provides
      insights into the morphological and chemical makeup of the three grains shedding
      light on the higher bio-accessibility of einkorn wheat nutrients compared to
      barley and oats, providing important suggestions for human nutrition and
      technological standpoints.

PMID- 29569871
TI  - LOX-1 deficient mice show resistance to zymosan-induced arthritis.
AB  - Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox
      LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of
      arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in
      arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in
      the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan
      injection. Saline was injected in the left knees. Arthritis development was
      evaluated using inflammatory cell infiltration, synovial hyperplasia, and
      cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox
      LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and
      chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3
      expression levels in synovial cells were scored on a grading scale. The positive
      cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The
      correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage
      degeneration score was also examined. Inflammatory cell infiltration, synovial
      hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1
      KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the
      saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox
      LDL expression in synovial cells and chondrocytes were detected in the knees of
      WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX
      1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in
      the synovial cells and chondrocytes was also detected in knees of both mice with
      ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The
      positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed
      a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system
      in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are
      potential therapeutic targets for arthritis prevention.

PMID- 29569872
TI  - Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is
      useful in diagnosis of HBV-related hepatocellular carcinoma with higher
      specificity and sensitivity.
AB  - Hepatocellular carcinoma is the third leading cause of cancer-related death
      worldwide and late diagnosis is the main cause of death in HCC patients. In this
      study expression patterns of HSP70, GPC3 and GS and their relationships with
      pathogenesis of HCC in Iranian patients were investigated. The expression of
      HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real
      time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC
      without HBV, HBV+HCC and 30 normal tissues as control group. HSP70, GPC3 and GS
      were expressed in higher levels in HBV-related HCC samples compared to HBV alone
      group. The results showed that the labeling index of HSP70, GPC3 and GS are
      correlated with immunohistochemical and molecular expressions of HSP70, GPC3 and
      GS. The sensitivity and specificity for HCC diagnosis were 43.4% and 89.7% for
      HSP70, 64.3% and 90.4% for GPC3, and 60.7% and 94.3% for GS, respectively. The
      sensitivity and specificity of the panels with 3, 2 and 1 positive markers,
      regardless of which one, were 21.6% and 100%, 51.3% and 100% and 93.4% and 80.5%
      respectively. The current study demonstrated an association between HSP70, GPC3
      and GS expressions and HBV-related HCC in our population. It was concluded that
      HSP70, GPC3 and GS expressions could be useful biomarkers for increasing the
      specificity and sensitivity of HCC diagnosis to acceptable level. Also, proper
      combinations of these 3 markers could improve diagnostic accuracy.

PMID- 29569873
TI  - The earthworm Dendrobaena veneta (Annelida): A new experimental-organism for
      photobiomodulation and wound healing.
AB  - Photobiomodulation (PBM) is a manipulation of cellular behavior using non
      ablative low intensity light sources. This manipulation triggers a cascade of
      metabolic effects and physiological changes resulting in improved tissue repair,
      of benefit in the treatment of tissue injury, degenerative or autoimmune
      diseases. PBM has witnessed an exponential increase in both clinical instrument
      technology and applications. It is therefore of benefit to find reliable
      experimental models to test the burgeoning laser technology for medical
      applications. In our work, we proposed the earthworm Dendrobaena veneta for the
      study of non-ablative laser-light effects on wound healing. In our preliminary
      work, D. veneta has been shown to be positively affected by PBM. New tests using
      D. veneta were set up to evaluate the effectiveness of a chosen 808 nm-64 J/cm2
      1W-CW laser therapy using the AB2799 hand-piece with flat-top bean profile, on
      the wound healing process of the earthworm. Effective outcome was assimilated
      through examining the macroscopic, histological, and molecular changes on the
      irradiated posterior-segment of excised-earthworms with respect to controls.
      Three successive treatments, one every 24 hours, were concluded as sufficient to
      promote the wound healing, by effects on muscular and blood vessel contraction,
      decrement of bacteria load, reduction of inflammatory processes and tissue
      degeneration. D. veneta was demonstrated to be a reliable experimental organism
      that meets well the 3Rs principles and the National Science Foundation statement.
      Through their genetic and evolutionary peculiarity, comparable to those of
      scientifically accredited models, D. veneta allows the effect of laser therapies
      by multidisciplinary methods, at various degree of complexity and costs to be
      investigated.

PMID- 29569874
TI  - Comparison of different histological protocols for the preservation and
      quantification of the intestinal mucus layer in pigs.
AB  - The histological characterization of the intestinal mucus layer is important for
      many scientific experiments investigating the interaction between intestinal
      microbiota, mucosal immune response and intestinal mucus production. The aim of
      this study was to examine and compare different fixation protocols for displaying
      and quantifying the intestinal mucus layer in piglets and to test which
      histomorphological parameters may correlate with the determined mucus layer
      thickness. Jejunal and colonal tissue samples of weaned piglets (n=10) were
      either frozen in liquid nitrogen or chemically fixed using methacarn solution.
      The frozen tissue samples were cryosectioned and subsequently postfixed using
      three different postfixatives: paraformaldehyde vapor, neutrally buffered
      formalin solution and ethanol solution. After dehydration, methacarn fixed
      tissues were embedded in paraffin wax. Both sections of cryopreserved and
      methacarn fixed tissue samples were stained with Alcian blue (AB)-PAS followed by
      the microscopically determination of the mucus layer thickness. Different pH
      values of the Alcian Blue staining solution and two mucus layer thickness
      measuring methods were compared. In addition, various histomorphological
      parameters of methacarn fixed tissue samples were evaluated including the number
      of goblet cells and the mucin staining area. Cryopreservation in combination with
      chemical postfixation led to mucus preservation in the colon of piglets allowing
      mucus thickness measurements. Mucus could be only partly preserved in
      cryosections of the jejunum impeding any quantitative description of the mucus
      layer thickness. The application of different postfixations, varying pH values of
      the AB solution and different mucus layer measuring methods led to comparable
      results regarding the mucus layer thickness. Methacarn fixation proved to be
      unsuitable for mucus depiction as only mucus patches were found in the jejunum or
      a detachment of the mucus layer from the epithelium was observed in the colon.
      Correlation analyses revealed that the proportion of the mucin staining area per
      crypt area (relative mucin staining) measured in methacarn fixed tissue samples
      corresponded to the colonal mucus layer thickness determined in cryopreserved
      tissue samples. In conclusion, the results showed that cryopreservation using
      liquid nitrogen followed by chemical postfixation and AB-PAS staining led to a
      reliable mucus preservation allowing a mucus thickness determination in the colon
      of pigs. Moreover, the detected relative mucin staining area may serve as a
      suitable histomorphological parameter for the assessment of the intestinal mucus
      layer thickness. The findings obtained in this study can be used for the
      implementation of an improved standard for the histological description of the
      mucus layer in the colon of pigs.

PMID- 29569875
TI  - Merkel-like cell distribution in the epithelium of the human vagina. An
      immunohistochemical and TEM study.
AB  - Human Merkel cells (MCs) were first described by Friedrich S. Merkel in 1875 and
      named "Tastzellen" (touch cells). Merkel cells are primarily localized in the
      basal layer of the epidermis and concentrated in touch-sensitive areas. In our
      previous work, we reported on the distribution of MCs in the human esophagus, so
      therefore we chose other parts of the human body to study them. We selected the
      human vagina, because it has a similar epithelium as the esophagus and plays very
      important roles in reproduction and sexual pleasure. Due to the fact that there
      are very few research studies focusing on the innervation of this region, we
      decided to investigate the occurrence of MCs in the anterior wall of the vagina.
      The aim of our research was to identify MCs in the stratified squamous non
      keratinized epithelium of the human vagina in 20 patients. For the identification
      of Merkel cells by light microscopy, we used antibodies against simple-epithelial
      cytokeratins (especially anti-cytokeratin 20). We also tried to identify them
      using transmission electron microscopy. Our investigation confirmed that 10 (50
      %) of 20 patients had increased number of predominantly intraepithelial CK20
      positive "Merkel-like" cells (MLCs) in the human vaginal epithelium.
      Subepithelial CK20 positive MLCs were observed in only one patient (5%). We tried
      to identify them also using transmission electron microscopy. Our investigation
      detected some unique cells that may be MCs. The purpose of vaginal innervation is
      still unclear. There are no data available concerning the distribution of MCs in
      the human vagina, so it would be interesting to study the role of MCs in the
      vaginal epithelium, in the context of innervation and epithelial biology.

PMID- 29569876
TI  - Seasonal expressions of androgen receptor, estrogen receptors and cytochrome P450
      aromatase in the uteri of the wild Daurian ground squirrels (Spermophilus
      dauricus).
AB  - The reproductive tissues including the uterus undergo dramatic changes in
      seasonal breeders from the breeding to non-breeding seasons. Classically, sex
      steroid hormones play important roles in the uterine morphology and functions. To
      clarify the relationship between sex steroid hormones and seasonal changes in the
      uterine morphology and functions, the wild Daurian ground squirrels (Spermophilus
      dauricus) were used as seasonal breeder model. And the immunolocalizations and
      expression levels of androgen receptor (AR), estrogen receptors alpha and beta
      (ERalpha and ERbeta) and cytochrome P450 aromatase (P450arom) were investigated
      in the uteri of the wild Daurian ground squirrels in the breeding (April) and the
      non-breeding (June) seasons via immunohistochemistry, Western blot and RT-PCR.
      Histologically, the uterine weight, the thickness of endometrium and the
      glandular density were significantly higher in the uteri of the breeding season
      than those of the non-breeding season. In both seasons, the immunostaining of AR
      was only presented in stromal cells of the uteri; the positive staining of
      ERalpha and ERbeta were localized in stromal cells and glandular cells; P450arom
      was merely immunolocalized in glandular cells. The protein and mRNA expression
      levels of ERalpha, ERbeta and P450arom were higher in the uteri of the breeding
      season than those of the non-breeding season; conversely, the expressions of AR
      were higher in the uteri of the non-breeding season comparing with those of the
      breeding season in both protein and mRNA levels. The AR: ER ratio in the uteri of
      the non-breeding season exceeded the AR: ER ratio in the uteri of the breeding
      season in the wild Daurian ground squirrels. These results suggested that
      seasonal changes in the expression levels of AR, ERs and P450arom might be
      correlated with the uterine morphology and histology changes, and estrogen may
      play an important autocrine/paracrine role in regulating the uterine functions of
      the wild Daurian ground squirrels.

PMID- 29569877
TI  - Hexavalents in spermatocytes of Robertsonian heterozygotes between Mus m.
      domesticus 2n=26 from the Vulcano and Lipari Islands (Aeolian Archipelago,
      Italy).
AB  - The size and shape of the chromosomes, as well as the chromosomal domains that
      compose them, are determinants in the distribution and interaction between the
      bivalents within the nucleus of spermatocytes in prophase I of meiosis. Thus the
      nuclear architecture characteristic of the karyotype of a species can be modified
      by chromosomal changes such as Rb chromosomes. In this study we analysed the
      meiotic prophase nuclear organization of the heterozygous spermatocytes from Mus
      musculus domesticus 2n=26, and the synaptic configuration of the hexavalent
      formed by the dependent Rb chromosomes Rbs 6.16, 16.10, 10.15, 15.17 and the
      telocentric chromosomes 6 and 17. Spreads of 88 pachytene spermatocytes from two
      males were studied and in all of them five metacentric bivalents, four
      telocentric bivalents, one hexavalent and the XY bivalent were observed. About
      48% of the hexavalents formed a chain or a ring of synapsed chromosomes, the
      latter closed by synapsis between the short arms of telocentric chromosomes 6 and
      17.  About 52% of hexavalents formed an open chain of 10 synapsed chromosomal
      arms belonging to 6 chromosomes.  In about half of the unsynapsed hexavalents one
      of the telocentric chromosome short arms appears associated with the X chromosome
      single axis, which was otherwise normally paired with the Y chromosome.  The
      cluster of pericentromeric heterochromatin mostly determines the hexavalent's
      nuclear configuration, dragging the centromeric regions and all the chromosomes
      towards the nuclear envelope similar to an association of five telocentric
      bivalents. These reiterated encounters between these chromosomes restrict the
      interactions with other chromosomal domains and might favour eventual
      rearrangements within the metacentric, telocentric or hexavalent chromosome
      subsets. The unsynapsed short arms of telocentric chromosomes frequently bound to
      the single axis of the X chromosome could further complicate the already complex
      segregation of hexavalent chromosomes.

PMID- 29569879
TI  - The penetration of methanol into bovine cardiac and hepatic tissues is faster
      than ethanol and formalin.
AB  - Methanol, ethanol and formalin are commonly used as fixatives to preserve
      biological tissues from decay in the preparation of histological sections.
      Fixation of the inner layers of the tissue depends on the ability of the fixative
      to diffuse into the tissue. It is unknown whether methanol penetrates tissues at
      similar rates to other fixatives. This study aimed to compare the penetration
      rates of methanol, ethanol and formalin into bovine heart and liver tissues. The
      penetration distance and tissue shrinkage or expansion were measured by analysing
      the digital images of tissue before and after immersion in different fixatives
      for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by
      Bonferroni's post-hoc test. The penetration distance of methanol was
      significantly greater in both heart and liver tissues compared with that of
      ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of
      both tissues (P>0.05). The penetration rate of formalin was similar to that of
      ethanol in both tissues however it was significantly slower than methanol (N=4,
      P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of
      methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801,
      respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The
      penetration coefficient of methanol was significantly greater than that of
      ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion,
      methanol penetrates tissue significantly faster than ethanol and formalin.

PMID- 29569882
TI  - HEART RATE REGULATION DURING ADAPTATION TO CONDITIONS IN ANTARCTICA.
AB  - The article deals with topical issues of the problem of studyingthe mechanisms of
      human adaptation to Antarctic conditions,in particular, the characteristics of
      the restructuring regulationof cardiovascular system during expedition activity
      atthe Ukrainian Antarctic Station "Academic Vernadsky". Thestudies were performed
      directly in Antarctica with the participationof winterers, who during a year were
      surveyed monthlyby cardiointervalography and ECG. As a result of analysis
      ofvariance of heart rate in Antarctic conditions we identified thephasic
      restructuring of the regulation of heart rhythm of winterers.The findings extend
      the understanding of the peculiaritiesof realization of regulating the
      circulatory system during thechange of adaptation phases. In particular, the RRNN
      indexhas a phasic structure and ranges +/- 7-9 c.u. from the beginningof
      wintering, and in the last phase is increased to -32 c.u. Theactivity of the
      development of stress condition among winterersreflects the dynamics of changes
      in the rate INt function,which from the beginning of wintering till January
      rangedfrom 2-5 c.u. by modulo, and in the months before the return(February,
      March), the rate reached 46 c.u. It is established adominant role of the time
      factor in influencing the quality adjustmentof adaptation processes. While during
      the first half ofthe expedition heart rate variability had a balanced
      regulatoryinfluence, at the end of the expedition an increased activityof the
      sympathetic division of the autonomic nervous systemand stress regulatory
      mechanisms were observed. This mayindicate for incomplete adaptation that
      requires the applicationof methods of correction of functional state.

PMID- 29569878
TI  - Energy Dispersive X-ray (EDX) microanalysis: A powerful tool in biomedical
      research and diagnosis.
AB  - The Energy Dispersive X-ray (EDX) microanalysis is a technique of elemental
      analysis associated to electron microscopy based on the generation of
      characteristic Xrays that reveals the presence of elements present in the
      specimens. The EDX microanalysis is used in different biomedical fields by many
      researchers and clinicians. Nevertheless, most of the scientific community is not
      fully aware of its possible applications. The spectrum of EDX microanalysis
      contains both semi-qualitative and semi-quantitative information. EDX technique
      is made useful in the study of drugs, such as in the study of drugs delivery in
      which the EDX is an important tool to detect nanoparticles (generally, used to
      improve the therapeutic performance of some chemotherapeutic agents). EDX is also
      used in the study of environmental pollution and in the characterization of
      mineral bioaccumulated in the tissues. In conclusion, the EDX can be considered
      as a useful tool in all works that require element determination, endogenous or
      exogenous, in the tissue, cell or any other sample.

PMID- 29569883
TI  - EXOCRINE FUNCTION OF THE LIVER IN RATS WITH EXPOSURE TO CORVITIN.
AB  - In acute experiments on rats with cannulated bile duct westudied the effect of
      Corvitin, water-soluble analogue ofquercetin, on secretion of bile. Intraportal
      administration ofthe test compound at doses of 2,5; 5 and 10 mg/kg resulted ina
      significant increase in the volume of secreted bile by 20,9,31,2 and 20,4%,
      respectively, as compared with the control. Using the method of thin layer
      chromatography it was establishedthe mild stimulating effect of Corvitin on the
      processesof bile acids conjugation with taurine and glycine, especiallywhen
      administered at a dose of 5 mg/kg. This flavonoid did notaffect the concentration
      of glycocholic acid, however increasedthe content of glycochenodeoxycholic and
      glycodeoxycholicacids in the mixture between 15 to 35,1%. Regarding free
      bileacids, the concentration of cholic acid, chenodeoxycholic anddeoxycholic
      acids in the mixture was increased significantlyrelative to control only after
      Corvitin application at dose 10 mg/kg. In the first case - from 17,9 to 29,8%, in
      the second - from25 to 65,4%. At the dose of 5 mg/kg, Corvitin
      significantlyincreased the ratio of bile cholates conjugation (maximum by23,2%),
      whereas 10 mg/kg of the drug decreased this indexby 27,0%. After administration
      of Corvitin, the hydroxylationratio in all experimental groups differed little
      from the control:at the dose of 5 and 10 mg/kg this parameter decreased by14%.
      Thus, Corvitin modulates exocrine function of the liver,causing an increase in
      bile secretion and concentration ofdifferent cholates, dose-dependently
      increasing or decreasingthe effectiveness of multienzyme systems providing
      processesof bile acids conjugation in rats.

PMID- 29569884
TI  - INFLUENCE OF HYPOXIC PRECONDITIONING ON THE MECHANISMS OF BLOOD OXYGEN TRANSPORT
      AND OXIDATIVE DAMAGESDURING HEPATIC ISCHEMIA-REPERFUSION IN RABBITS.
AB  - The effect of hypoxic preconditioning (HP) on the bloodoxygen-binding properties
      and liver oxidative damages wasdetermine during hepatic ischemia-reperfusion
      (HIR) in rabbits.Animals were randomized into two experimental groups:1st (HIR) -
      hepatic ischemia (30 min by Pringle maneuver) andreperfusion (120 min); 2nd
      (HP+HIR) - before HIR the rabbitswere passed through hypoxic chamber at 3500 m
      altitude during1 hr/day (3 times day after day). The parameters of bloodoxygen
      transport (r50, rSO2, rO2, rN, HCO3-, ABE and ect.),lipid peroxidation products
      (conjugated dienes, Schiff bases)and blood hepatic markers (ALT, AST) were
      detected. It'sfound that HIR leads to decline in hemoglobin oxygen
      affinity,activation of lipid peroxidation processes and elevation of ALTand AST
      activities in the 1st group. Hypoxic preconditioning(2nd group) markedly
      increased hemoglobin oxygen affinity,reduced the lipid peroxidation processes and
      ALT and ASTactivities in the blood during HIR. Thus, HP has a protectiveeffect
      during HIR through elevation of hemoglobin oxygenaffinity and declining hepatic
      oxidative damages.

PMID- 29569885
TI  - BONE TISSUE REMODELING AFTER THE INTRODUCTION OF EXOGENOUS MELATONIN IN DIFFERENT
      SEASONS.
AB  - We studied the impact of pharmacological doses (5 mg / kg) ofmelatonin on the
      parameters of bone remodeling in 3 month-oldmale Wistar rats in autumn and
      spring. In autumn experiments,introduction of melatonin to young rats caused an
      increase ofalkaline phosphatase by 43,9% and hialuronidase activity by15,4% and
      decreased the content of glycosaminoglycans by46,7%. The concentration of total
      lipids and triglycerides wasdecreased. In spring, the introduction of melatonin
      to youngrats inhibited the physiological remodeling of bone tissue,reduced the
      activity of alkaline phosphatase and increasedthe activity of acid on the 78% and
      tartrate resistant acidphosphatases by 72% regardless of the oxygen
      consumptionlevel. The concentration of glycosaminoglycans and free aminoacids
      increased. Such changes may disturb the integrity of theorganic matrix and reduce
      the fixation of inorganic componentof connective tissue - hydroxyapatite
      crystals.

PMID- 29569886
TI  - BONE REGULATORY MECHANISMS DESTRUCTION IN EXPERIMENTAL CHRONIC KIDNEY DISEASE.
AB  - The aim of our study was to investigate the role of intercellularmediators -
      interleukin-1 receptor antagonist (IL-1 RA),interleukin-17 (IL-17), receptor
      activator of nuclear factor kBligand (RANKL) and osteoprotegerin in the
      mechanisms ofmetabolic regulation of renal and bone tissue on model of
      violationsof bone remodeling in chronic kidney disease (CKD).It was found a
      significant increase in the content of cytokinesIL-1 RA (4,207 +/- 0,546 pg/ml),
      IL-17 (33,944 +/- 0,938 pg/ml), osteoprotegerin (28,338 +/- 1,223 pg/ml) and
      RANKL(0,184 +/- 0,018 pmol/l) in the serum of animals in violationof bone
      remodeling in CKD compared with the contents ofthe studied cytokines in animals
      in the control group (2,529+/- 0,132 pg/ml, 28,166 +/- 0,526 pg/ml, 21,588 +/-
      0,763 pg/mland 0,131 +/- 0,006 pmol/l, respectively) (P<0.05). The
      obtainedcorrelations reflect the relationship between regulation of
      boneremodeling and the development of inflammation in CKD.The imbalance between
      pro- and anti-inflammatory cytokineplays an important role both in the
      development of CKD andin processes of bone remodeling.

PMID- 29569887
TI  - FEATURES OF LIMBIC-NEOCORTICAL AND MONOAMINERGIC CORRELATIONS IN THE DEVELOPMENT
      OF WITHDRAWALSYNDROME OF INHALATIONS OF VAPORS OF ORGANIC SOLVENT "646" IN RATS.
AB  - The aim of the work was to study the limbic-neocortical andmonoaminergic features
      of the development of withdrawalsyndrome of volatile organic compounds (VOC)
      inhalationsin rats. The study was carried out in 30 three months oldmale rats
      with dependence on inhalations of organic solvent"646" which contains up to 50 %
      mix of toluene and acetone.It has been shown that the withdrawal syndrome of
      inhalantis characterized by increased excitability and behavioralmanifestations
      of equivalents of convulsive reactions such asoral hyperkinesis, head shaking and
      changes in the frequencyamplitudespectrum of the biopotentials in structures of
      thebrain limbic-neocortical system with the initiation in the medialolfactory
      region and hippocampus. At the hypothalamus level,withdrawal of VOC inhalations
      produces the depleting impacton the catecholaminergic structures with a stronger
      effect inneuronal endings with adrenaline as neurotransmitter. Withdrawalsyndrome
      evokes a significant decrease in dopaminecontent by 61 %, noradrenaline by 77 %
      and adrenaline by 92% in the hypothalamus and increase in serotonin
      concentrationin blood serum by 16 % in rats with initial preference toinhalations
      of organic solvent "646". In rats with the absenceof initial preference to
      inhalations of organic solvent "646"a decrease in adrenaline level in the
      hypothalamus by 77 %was detected.

PMID- 29569888
TI  - PROSPECTS OF C60 FULLERENE APPLICATION AS A MEAN OF PREVENTION AND CORRECTION OF
      ISCHEMIC-REPERFUSION INJURYIN THE SKELETAL MUSCLE TISSUE.
AB  - lack of accurate diagnostic tests for the rapid detection ofischemic injury
      remains an urgent problem. In this context,a search for specific markers of
      ischemia as well as newtherapeutic agents for prevention and treatment of
      ischemicinjury continues. Water-soluble nano-sized C60 fullerenes, aspowerful
      antioxidants, can act as promising means for correctionof various muscle system
      states, in the base of which liethe destructive effects of free radicals.

PMID- 29569889
TI  - Fitness and therapeutic potential of intermittent hypoxia training: a matter of
      dose.
AB  - The introduction of different methods of intermittent hypoxic training (IHT) into
      fitness, sports, militaryand medical practice has raised a lot of questions about
      the most beneficial regimens of such treatmentand their optimal instrumental
      implementation. Low doses of hypoxia might not be sufficient stimuli tomobilize
      adaptive mechanisms, while severe or prolonged hypoxia may provoke dangerous
      pathologicalprocesses. In this review, we pay attention to narrow practical
      question of the most effective and convenienttechnology of IHT implementation,
      notably the inhalation of hypoxic gas mixtures. Data strongly suggestthat in
      humans the training with 15-13% inhaled oxygen (FiO2) at various time
      characteristics does notprovide marked positive changes. Short-term daily
      sessions consisting 3-4 bouts of 5-7 min exposures to12-10% FiO2 alternating with
      equal durations of normoxia for 2-3 weeks have been shown as a mostbeneficial
      without maladaptive consequences for fitness and treatment of some diseases. More
      severe orlonger intermittent hypoxia protocols must be accompanied by strict
      monitoring of blood oxygen saturation(SpO2), electrocardiogram, breathing pattern
      and arterial blood pressure in order to avoid unexpectedundesirable individual
      reactions. For sports purposes, the reduction of oxygen content to
      individuallytolerable level for some minutes is justified as far as it maximizes
      benefits. However, such regimen requirespreliminary diagnostics of individual
      hypoxic tolerance and cardio-respiratory reactivity as well as rigorousmonitoring
      of vital functions during IHT and good feedback device. The use of oxygen
      concentrations below12% for treatment of diseases, especially in children and the
      elderly, are required substantial additionalresearch. Recently, a new mode of
      adaptive training was explored, which combines periods of hypoxia(12-10% FiO2)
      and hyperoxia (30-35% FiO2). Limited evidences suggest that such regime can
      reduce thetime of recovery periods, that is shorten the duration of sessions.
      However, there is still no strong comparativeevidence for humans that this method
      is much more efficient than hypoxic-normoxic mode. We appeal to allscientists
      working in the field of IHT not to hide their negative results but publish all
      observations in the openpress. It will make a significant contribution in
      developing of common guidelines for IHT implementationto improve public health of
      our Planet.

PMID- 29569890
TI  - Symmetric Sodium-Ion Capacitor Based on Na0.44MnO2 Nanorods for Low-Cost and High
      Performance Energy Storage.
AB  - Batteries and electrochemical capacitors play very important roles in the
      portable electronic devices and electric vehicles and have shown promising
      potential for large-scale energy storage applications. However, batteries or
      capacitors alone cannot meet the energy and power density requirements because
      rechargeable batteries have a poor power property, whereas supercapacitors offer
      limited capacity. Here, a novel symmetric sodium-ion capacitor (NIC) is developed
      based on low-cost Na0.44MnO2 nanorods. The Na0.44MnO2 with unique
      nanoarchitectures and iso-oriented feature offers shortened diffusion path
      lengths for both electronic and Na+ transport and reduces the stress associated
      with Na+ insertion and extraction. Benefiting from these merits, the symmetric
      device achieves a high power density of 2432.7 W kg-1, an improved energy density
      of 27.9 Wh kg-1, and a capacitance retention of 85.2% over 5000 cycles.
      Particularly, the symmetric NIC based on Na0.44MnO2 permits repeatedly reverse
      polarity characteristics, thus simplifying energy management system and greatly
      enhancing the safety under abuse condition. This cost-effective, high-safety, and
      high-performance symmetric NIC can balance the energy and power density between
      batteries and capacitors and serve as an electric power source for future low
      maintenance large-scale energy storage systems.

PMID- 29569891
TI  - High-Performance Supercapacitor of Graphene Quantum Dots with Uniform Sizes.
AB  - Graphene quantum dots (GQDs) with uniform sizes of less than 5 nm are synthesized
      by a novel top-down strategy. Nitric acid as a strong oxidant can be used to cut
      graphene oxide via sonication and hydrothermal processes. Moreover, purified GQDs
      are obtained from removing oxygen-containing functional groups in a heat
      treatment process. Both nanoscale size and edge effect of GQDs improve their
      abundant active sites and restrain the restack of graphene nanosheets. Meanwhile,
      their electrochemical performance demonstrates the properties of the GQDs for
      practical application in energy storage. The GQD electrode material shows an
      ideal electric double-layer capacitance behavior such as a high specific
      capacitance of 296.7 F g-1, a satisfactory energy density of 41.2 W h kg-1 at 1 A
      g-1, a low internal resistance, a small relaxation time, and an excellent cycling
      stability. The results illustrate excellent electrochemical activity, high
      conductivity, and enhanced ion transport rate on the surface of electrolyte and
      electrode. The advantages of GQDs confirm their unique characteristics for
      potential applications in the field of electrode materials for supercapacitors.

PMID- 29569892
TI  - In Situ Plating of Porous Mg Network Layer to Reinforce Anode Dendrite
      Suppression in Li-Metal Batteries.
AB  - Li dendrite suppression enables a highly reversible Li-metal battery. However the
      strategy to smooth Li surface, especially under long-term cycling and high
      current density, is still a big challenge. Here, we propose a facile additive
      strategy to reinforce Li dendrite inhibition in a range of ether and carbonate
      electrolytes. Dissoluble Mg(TFSI)2 is employed as a degradable electrolyte
      additive, leading to in situ plating of porous Mg network when contacting
      reductive Li atoms. Mg adatoms with extremely low diffusion energy barrier as
      lithiophilic sites enable a smooth or flaky morphology of Li surface even under a
      high current density of 2 mA/cm2 and high capacity of 6 mAh/cm2. Mg-salt additive
      significantly extends the cycling life of Li||Cu asymmetric cells up to 240 and
      200 cycles for carbonate and ether electrolytes, respectively. Under a current
      density as high as 5 mA/cm2, the Li||Cu cell based on ether system can still
      survive up to 140 cycles with a small voltage hysteresis close to 60 mV. The
      hysteresis can be reduced to below 25 mV for lasting 200 cycles at 1 mA/cm2. This
      additive strategy provides a facile solution to in situ construction of
      conductive anode-electrolyte interface with low interface resistance for
      alleviating uneven Li nucleation.

PMID- 29569893
TI  - High-Throughput Generation of Durable Droplet Arrays for Single-Cell
      Encapsulation, Culture, and Monitoring.
AB  - High-throughput measurements can be achieved using droplet-based assays. In this
      study, we exploited the principles of wetting behavior and capillarity to guide
      liquids sliding along a solid surface with hybrid wettability. Oil-covered
      droplet arrays with uniformly sized and regularly shaped picoliter droplets were
      successfully generated on hydrophilic-in-hydrophobic patterned substrates. More
      than ten thousand 31-pL droplets were generated in 5 s without any sophisticated
      instruments. Covering the droplet arrays with oil during generation not only
      isolated the droplets from each other but also effectively prevented droplet
      evaporation. The oil-covered droplet arrays could be stored for more than 2 days
      with less than 35% volume loss. Single microspheres, microbial cells, or
      mammalian cells were successfully captured in the droplets. We demonstrate that
      Escherichia coli could be encapsulated at a certain number (1-4) and cultured for
      3 days in droplets. Cell population and morphology were dynamically tracked
      within individual droplets. Our droplet array generation method enables high
      throughput processing and is facile, efficient, and low-cost; in addition, the
      prepared droplet arrays have enormous potential for applications in chemical and
      biological assays.

PMID- 29569894
TI  - Lateral Heterostructures Formed by Thermally Converting n-Type SnSe2 to p-Type
      SnSe.
AB  - Different two-dimensional (2D) materials, when combined together to form
      heterostructures, can exhibit exciting properties that do not exist in individual
      components. Therefore, intensive research efforts have been devoted to their
      fabrication and characterization. Previously, vertical and in-plane 2D
      heterostructures have been formed by mechanical stacking and chemical vapor
      deposition. Here, we report a new material system that can form in-plane p-n
      junctions by thermal conversion of n-type SnSe2 to p-type SnSe. Through scanning
      tunneling microscopy and density functional theory studies, we find that these
      two distinctively different lattices can form atomically sharp interfaces and
      have a type II to nearly type III band alignment. We also demonstrate that this
      method can be used to create micron-sized in-plane p-n junctions at predefined
      locations. These findings pave the way for further exploration of the intriguing
      properties of the SnSe2-SnSe heterostructure.

PMID- 29569895
TI  - On the Correlation between the Microscopic Structure and Properties of Phosphate
      Cross-Linked Chitosan Gels.
AB  - Ionic chitosan gels fabricated using multivalent anions, tripolyphosphate (TPP)
      or pyrophosphate (PPi), respectively, have been investigated as potential
      biomaterials to be used in tissue engineering. Starting from the hypothesis that
      the polymer mesh texture at the microscale affects the final performance of the
      resulting materials, an innovative image analysis approach is presented in the
      first part of the article, which is aimed at deriving quantitative information
      from transmission electron microscopy images. The image analysis of the (more
      extended) central area of the gel networks revealed differences between both the
      cross-linking densities and pore size distributions of the two systems, the TPP
      gels showing a higher connectivity. Chitosan-TPP gels showed a limited
      degradation in simulated physiological media up to 6 weeks, reasonably ascribed
      to the texture of the (more extended) central area of the gels, whereas PPi
      counterparts degraded almost immediately. The release profiles and the
      calculation of diffusion coefficients for bovine serum albumin and cytochrome c,
      herein used as model payloads, indicated a different release behavior depending
      on the polymer network homogeneity/inhomogeneity and molecular weight of loaded
      molecules. This finding was ascribed to the marked inhomogeneity of the PPi gels
      (at variance with the TPP ones), which had been demonstrated in our previous
      work. Finally, thorough in vitro studies demonstrated good biocompatibility of
      both chitosan gels, and because of this feature, they can be used as suitable
      scaffolds for cellular colonization and metabolic activity.

PMID- 29569896
TI  - Electrolytic CO2 Reduction in a Flow Cell.
AB  - Electrocatalytic CO2 conversion at near ambient temperatures and pressures offers
      a potential means of converting waste greenhouse gases into fuels or commodity
      chemicals (e.g., CO, formic acid, methanol, ethylene, alkanes, and alcohols).
      This process is particularly compelling when driven by excess renewable
      electricity because the consequent production of solar fuels would lead to a
      closing of the carbon cycle. However, such a technology is not currently
      commercially available. While CO2 electrolysis in H-cells is widely used for
      screening electrocatalysts, these experiments generally do not effectively report
      on how CO2 electrocatalysts behave in flow reactors that are more relevant to a
      scalable CO2 electrolyzer system. Flow reactors also offer more control over
      reagent delivery, which includes enabling the use of a gaseous CO2 feed to the
      cathode of the cell. This setup provides a platform for generating much higher
      current densities ( J) by reducing the mass transport issues inherent to the H
      cells. In this Account, we examine some of the systems-level strategies that have
      been applied in an effort to tailor flow reactor components to improve
      electrocatalytic reduction. Flow reactors that have been utilized in CO2
      electrolysis schemes can be categorized into two primary architectures: Membrane
      based flow cells and microfluidic reactors. Each invoke different dynamic
      mechanisms for the delivery of gaseous CO2 to electrocatalytic sites, and both
      have been demonstrated to achieve high current densities ( J > 200 mA cm-2) for
      CO2 reduction. One strategy common to both reactor architectures for improving J
      is the delivery of CO2 to the cathode in the gas phase rather than dissolved in a
      liquid electrolyte. This physical facet also presents a number of challenges that
      go beyond the nature of the electrocatalyst, and we scrutinize how the judicious
      selection and modification of certain components in microfluidic and/or membrane
      based reactors can have a profound effect on electrocatalytic performance. In
      membrane-based flow cells, for example, the choice of either a cation exchange
      membrane (CEM), anion exchange membrane (AEM), or a bipolar membrane (BPM)
      affects the kinetics of ion transport pathways and the range of applicable
      electrolyte conditions. In microfluidic cells, extensive studies have been
      performed upon the properties of porous carbon gas diffusion layers, materials
      that are equally relevant to membrane reactors. A theme that is pervasive
      throughout our analyses is the challenges associated with precise and controlled
      water management in gas phase CO2 electrolyzers, and we highlight studies that
      demonstrate the importance of maintaining adequate flow cell hydration to achieve
      sustained electrolysis.

PMID- 29569897
TI  - Low-Power All-Organic Electrophoretic Display Using Self-Assembled Charged Poly(
      t-butyl methacrylate) Microspheres in Isoparaffinic Fluid.
AB  - The increasing demands for display devices with low power consumption and outdoor
      readability have stimulated comprehensive research into full-color reflective
      displays that employ color-tunable photonic crystal technologies. Although the
      recently developed crystalline colloidal arrays (CCAs) of the charged
      microspheres have shown the outstanding color tunability, the practical
      application is limited because the use of highly polar liquid medium such as
      water is required to maintain the charges on the surface of microsphere, whereas
      it is not suitable for long-term use in an electric field. Herein, a self
      assembled CCA from charged poly( t-butyl methacrylate) microspheres was
      successfully fabricated, which was stabilized by the charged inverse micelles of
      sodium di-2-ethylhexyl-sulfosuccinate in a nonpolar isoparaffinic fluid. A
      charged all-organic CCA was found to exhibit full-color tunability with a 1000
      fold reduction in the power consumption (~6 MUW cm-2) under a direct current
      voltage bias of 4 V in comparison to that in an aqueous system, which is a
      promising feature for a low-power-consumption display device.

PMID- 29569898
TI  - Boosting Light Harvesting in Perovskite Solar Cells by Biomimetic Inverted
      Hemispherical Architectured Polymer Layer with High Haze Factor as an
      Antireflective Layer.
AB  - Biomimetic microarchitectured polymer layers, such as inverted hemispherical
      architectured (IHSA)-polydimethylsiloxane (PDMS) and hemispherical architectured
      (HSA)-PDMS layers, were prepared by a simple and cost-effective soft-imprinting
      lithography method via a hexagonal close-packed polystyrene microsphere
      array/silicon mold. The IHSA-PDMS/glass possessed superior antireflection (AR)
      characteristics with the highest/lowest average transmittance/reflectance ( Tavg/
      Ravg) values of approximately 89.2%/6.4% compared to the HSA-PDMS/glass, flat
      PDMS/glass, and bare glass ( Tavg/ Ravg ~88.8%/7.5%, 87.5%/7.9%, and 87.3%/8.8%,
      respectively). In addition, the IHSA-PDMS/glass also exhibited a relatively
      strong light-scattering property with the higher average haze ratio ( Havg) of
      ~38% than those of the bare glass, flat-PDMS/glass, and HSA-PDMS/glass (i.e.,
      Havg ~ 1.1, 1.7, and 34.2%, respectively). At last, to demonstrate the practical
      feasibility under light control of the solar cells, the IHSA-PDMS was laminated
      onto the glass substrates of perovskite solar cells (PSCs) as an AR layer, and
      their device performances were explored. Consequently, the short-circuit current
      density of the PSCs integrated with the IHSA-PDMS AR layer was improved by ~17%
      when compared with the device without AR layer, resulting in the power conversion
      efficiency (PCE) up to 19%. Therefore, the IHSA-PDMS is expected to be applied as
      an AR layer for solar cells to enhance their light absorption as well as the PCE.

PMID- 29569899
TI  - Tip-Selective Growth of Silver on Gold Nanostars for Surface-Enhanced Raman
      Scattering.
AB  - Nanogaps as "hot spots" with highly localized surface plasmon can generate
      ultrastrong electromagnetic fields. Superior to the exterior nanogaps obtained
      via aggregation and self-assembly, interior nanogaps within Au and Ag
      nanostructures give stable and reproducible surface-enhanced Raman scattering
      (SERS) signals. However, the synthesis of nanostructures with interior hot spots
      is still challenging because of the lack of high-yield strategies and clear
      design principles. Herein, gold-silver nanoclusters (Au-Ag NCs) with multiple
      interior hot spots were fabricated as SERS platforms via selective growth of Ag
      nanoparticles on the tips of Au nanostars (Au NSs). Furthermore, the interior gap
      sizes of Au-Ag NCs can be facilely tuned by changing the amount of AgNO3 used.
      Upon 785 nm excitation, single Au-Ag NC350 exhibits 43-fold larger SERS
      enhancement factor and the optimal signal reproducibility relative to single Au
      NS. The SERS enhancement factors and signal reproducibility of Au-Ag NCs increase
      with the decrease of gap sizes. Collectively, the Au-Ag NCs could serve as a
      flexible, reproducible, and active platform for SERS investigation.

PMID- 29569901
TI  - Bioderived Three-Dimensional Hierarchical Nanostructures as Efficient Surface
      Enhanced Raman Scattering Substrates for Cell Membrane Probing.
AB  - In this work, we propose the use of complex, bioderived nanostructures as
      efficient surface-enhanced Raman scattering (SERS) substrates for chemical
      analysis of cellular membranes. These structures were directly obtained from a
      suitable gold metalization of the Pseudonitzchia multistriata diatom silica shell
      (the so called frustule), whose grating-like geometry provides large light
      coupling with external radiation, whereas its extruded, subwavelength lateral
      edge provides an excellent interaction with cells without steric hindrance. We
      carried out numerical simulations and experimental characterizations of the
      supported plasmonic resonances and optical near-field amplification. We
      thoroughly evaluated the SERS substrate enhancement factor as a function of the
      metalization parameters and finally applied the nanostrucures for discriminating
      cell membrane Raman signals. In particular, we considered two cases where the
      membrane composition plays a fundamental role in the assessment of several
      pathologies, that is, red blood cells and B-leukemia REH cells.

PMID- 29569900
TI  - Selective Determination of Cr(VI) by Glutaraldehyde Cross-Linked Chitosan Polymer
      Fluorophores.
AB  - Selective determination of aquatic chromium is critically important because of
      the dramatic differences in health and environment impacts by trivalent and
      hexavalent forms of chromium; however, it is challenging. In this work, for the
      first time, a nonconjugated polymer fluorophore (GCPF) was synthesized by cross
      linking chitosan with glutaraldehyde via Schiff base reactions and systematically
      investigated for selective determination of Cr(VI). The results revealed that the
      synthesized GCPF exhibited excellent photostability and water solubility. More
      importantly, GCPF possessed dramatically enhanced fluorescence intensity
      originated from the n-pi* transitions of the Schiff base subfluorophore groups
      (e.g., C?N) that can be selectively and sensitively quenched by Cr(VI) through
      oxidative damages to C?N group. An effective EDTA masking agent approach was
      employed to minimize ionic interferences. In the presence of high concentration
      of interference ions including Cr(III), the quenching GCPF fluorescence is
      capable of selectively determining Cr(VI) within a concentration range up to 50
      MUM and a detection limit of 0.22 MUM. The analytical performance of GCPF was
      also confirmed by analyzing real surface water and industrial samples.

PMID- 29569902
TI  - Tuning Electrochemical Properties of Li-Rich Layered Oxide Cathodes by Adjusting
      Co/Ni Ratios and Mechanism Investigation Using in situ X-ray Diffraction and
      Online Continuous Flow Differential Electrochemical Mass Spectrometry.
AB  - Owing to high specific capacity of ~250 mA h g-1, lithium-rich layered oxide
      cathode materials (Li1+ xNi yCo zMn(3- x-2 y-3 z)/4O2) have been considered as
      one of the most promising candidates for the next-generation cathode materials of
      lithium ion batteries. However, the commercialization of this kind of cathode
      materials seriously restricted by voltage decay upon cycling though Li-rich
      materials with high cobalt content have been widely studied and show good
      capacity. This research successfully suppresses voltage decay upon cycling while
      maintaining high specific capacity with low Co/Ni ratio in Li-rich cathode
      materials. Online continuous flow differential electrochemical mass spectrometry
      (OEMS) and in situ X-ray diffraction (XRD) techniques have been applied to
      investigate the structure transformation of Li-rich layered oxide materials
      during charge-discharge process. The results of OEMS revealed that low Co/Ni
      ratio lithium-rich layered oxide cathode materials released no lattice oxygen at
      the first charge process, which will lead to the suppression of the voltage decay
      upon cycling. The in situ XRD results displayed the structure transition of
      lithium-rich layered oxide cathode materials during the charge-discharge process.
      The Li1.13Ni0.275Mn0.580O2 cathode material exhibited a high initial medium
      discharge voltage of 3.710 and a 3.586 V medium discharge voltage with the lower
      voltage decay of 0.124 V after 100 cycles.

PMID- 29569903
TI  - Highly Sensitive and Automated Surface Enhanced Raman Scattering-based
      Immunoassay for H5N1 Detection with Digital Microfluidics.
AB  - Digital microfluidics (DMF) is a powerful platform for a broad range of
      applications, especially immunoassays having multiple steps, due to the
      advantages of low reagent consumption and high automatization. Surface enhanced
      Raman scattering (SERS) has been proven as an attractive method for highly
      sensitive and multiplex detection, because of its remarkable signal amplification
      and excellent spatial resolution. Here we propose a SERS-based immunoassay with
      DMF for rapid, automated, and sensitive detection of disease biomarkers. SERS
      tags labeled with Raman reporter 4-mercaptobenzoic acid (4-MBA) were synthesized
      with a core@shell nanostructure and showed strong signals, good uniformity, and
      high stability. A sandwich immunoassay was designed, in which magnetic beads
      coated with antibodies were used as solid support to capture antigens from
      samples to form a beads-antibody-antigen immunocomplex. By labeling the
      immunocomplex with a detection antibody-functionalized SERS tag, antigen can be
      sensitively detected through the strong SERS signal. The automation capability of
      DMF can greatly simplify the assay procedure while reducing the risk of exposure
      to hazardous samples. Quantitative detection of avian influenza virus H5N1 in
      buffer and human serum was implemented to demonstrate the utility of the DMF-SERS
      method. The DMF-SERS method shows excellent sensitivity (LOD of 74 pg/mL) and
      selectivity for H5N1 detection with less assay time (<1 h) and lower reagent
      consumption (~30 MUL) compared to the standard ELISA method. Therefore, this DMF
      SERS method holds great potentials for automated and sensitive detection of a
      variety of infectious diseases.

PMID- 29569904
TI  - Purification of Semiconducting Polymer Dots by Size Exclusion Chromatography
      Prior to Cytotoxicity Assay and Stem Cell Labeling.
AB  - Semiconducting polymer dots (Pdots) as fluorescent probes have shown promising
      applications because of their excellent optical properties. However, apparent
      differences were observed in cytotoxicity assays, which might originate from
      impurities introduced in polymer synthesis or nanoparticle preparation. A simple
      gel-filtration-based purification method was used to address this issue. Purified
      Pdots displayed obviously decreased cytotoxicity as compared with the same batch
      of unpurified Pdots. The purified Pdots were further examined in a cytotoxicity
      study on mesenchymal stem cells (MSCs), which are very sensitive to exogenous
      probes. The results indicated that purified Pdots did not affect the
      proliferation ability of MSCs, while unpurified Pdots could have obvious
      cytotoxicity. In addition, the purified Pdots did not show cytotoxicity even
      after 6 months of storage. Our results demonstrated that gel filtration is an
      effective method for obtaining Pdots with minimal cytotoxicity, which are more
      suitable for biological applications.

PMID- 29569906
TI  - Coordination Chemistry of a Strongly-Donating Hydroxylamine with Early Actinides:
      An Investigation of Redox Properties and Electronic Structure.
AB  - Separations of f-block elements are a critical aspect of nuclear waste
      processing. Redox-based separations offer promise, but challenges remain in
      stabilizing and differentiating actinides in high oxidation states. The
      investigation of new ligand types that provide thermodynamic stabilization to
      high-valent actinides is essential for expanding their fundamental chemistry and
      to elaborate new separation techniques and storage methods. We report herein the
      preparation and characterization of Th and U complexes of the pyridyl
      hydroxylamine ligand, N- tert-butyl- N-(pyridin-2-yl)hydroxylamine (pyNO-).
      Electrochemical studies performed on the homoleptic complexes [M(pyNO)4] (M = Th,
      U) revealed significant stabilization of the U complex upon one-electron
      oxidation. The salt [U(pyNO)4]+ was isolated by chemical oxidation of [U(pyNO)4];
      spectroscopic and computational data support assignment as a UV cation.

PMID- 29569905
TI  - Novel Antihypertensive Prodrug from Grape Seed Proanthocyanidin Extract via Acid
      Mediated Depolymerization in the Presence of Captopril: Synthesis, Process
      Optimization, and Metabolism in Rats.
AB  - Grape seed extract contains a high content of proanthocyanidins that can be
      depolymerized into C-4-substituted (epi)catechin derivatives in the presence of
      nucleophiles. However, the biological and medicinal values of depolymerization
      products have been rarely investigated. Recently, we developed a novel
      depolymerization product (-)-epicatechin-4beta- S-captopril methyl ester (ECC)
      derived from the reaction of grape seed proanthocyanidin extract with captopril
      in the presence of acidified methanol. A central composite design was employed to
      select the most appropriate depolymerization temperature and time to obtain the
      target product ECC with a high yield. A total of 16 metabolites of ECC in rat
      urine, feces, and plasma were identified using liquid chromatography quadrupole
      time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC
      could release captopril methyl ester and epicatechin, followed by the generation
      of further metabolites captopril and epicatechin sulfate conjugates. Therefore,
      ECC may be used as a potential prodrug with synergistic or additive hypotensive
      effects.

PMID- 29569907
TI  - Design and Mechanism of GABA Aminotransferase Inactivators. Treatments for
      Epilepsies and Addictions.
AB  - When the brain concentration of the inhibitory neurotransmitter gamma
      aminobutyric acid (GABA) diminishes below a threshold level, the excess neuronal
      excitation can lead to convulsions. This imbalance in neurotransmission can be
      corrected by inhibition of the enzyme gamma-aminobutyric acid aminotransferase
      (GABA-AT), which catalyzes the conversion of GABA to the excitatory
      neurotransmitter l-glutamic acid. It also has been found that raising GABA levels
      can antagonize the rapid elevation and release of dopamine in the nucleus
      accumbens, which is responsible for the reward response in addiction. Therefore,
      the design of new inhibitors of GABA-AT, which increases brain GABA levels, is an
      important approach to new treatments for epilepsy and addiction. This review
      summarizes findings over the last 40 or so years of mechanism-based inactivators
      (unreactive compounds that require the target enzyme to catalyze their conversion
      to the inactivating species, which inactivate the enzyme prior to their release)
      of GABA-AT with emphasis on their catalytic mechanisms of inactivation, presented
      according to organic chemical mechanism, with minimal pharmacology, except where
      important for activity in epilepsy and addiction. Patents, abstracts, and
      conference proceedings are not covered in this review. The inactivation
      mechanisms described here can be applied to the inactivations of a wide variety
      of unrelated enzymes.

PMID- 29569908
TI  - Optimization of Uranium-Doped Americium Oxide Synthesis for Space Application.
AB  - Americium 241 is a potential alternative to plutonium 238 as an energy source for
      missions into deep space or to the dark side of planetary bodies. In order to use
      the 241Am isotope for radioisotope thermoelectric generator or radioisotope
      heating unit (RHU) production, americium materials need to be developed. This
      study focuses on the stabilization of a cubic americium oxide phase using uranium
      as the dopant. After optimization of the material preparation,
      (Am0.80U0.12Np0.06Pu0.02)O1.8 has been successfully synthesized to prepare a 2.96
      g pellet containing 2.13 g of 241Am for fabrication of a small scale RHU
      prototype. Compared to the use of pure americium oxide, the use of uranium-doped
      americium oxide leads to a number of improvements from a material properties and
      safety point of view, such as good behavior under sintering conditions or under
      alpha self-irradiation. The mixed oxide is a good host for neptunium (i.e., the
      241Am daughter element), and it has improved safety against radioactive material
      dispersion in the case of accidental conditions.

PMID- 29569909
TI  - Thiol Reactivity of Curcumin and Its Oxidation Products.
AB  - The polypharmacological effects of the turmeric compound curcumin may be partly
      mediated by covalent adduction to cellular protein. Covalent binding to small
      molecule and protein thiols is thought to occur through a Michael-type addition
      at the enone moiety of the heptadienedione chain connecting the two methoxyphenol
      rings of curcumin. Here we show that curcumin forms the predicted thiol-Michael
      adducts with three model thiols, glutathione, N-acetylcysteine, and beta
      mercaptoethanol. More abundant, however, are respective thiol adducts of the
      dioxygenated spiroepoxide intermediate of curcumin autoxidation. Two
      electrophilic sites at the quinone-like ring of the spiroepoxide are identified.
      Addition of beta-mercaptoethanol at the 5'-position of the ring gives a 1,7
      dihydroxycyclopentadione-5' thioether, and addition at the 1'-position results in
      cleavage of the aromatic ring from the molecule, forming methoxyphenol-thioether
      and a tentatively identified cyclopentadione aldehyde. The curcuminoids demethoxy
      and bisdemethoxycurcumin do not form all of the possible thioether adducts,
      corresponding with their increased stability toward autoxidation. RAW264.7
      macrophage-like cells activated with phorbol ester form curcumin-glutathionyl and
      the 1,7-dihydroxycyclopentadione-5'-glutathionyl adducts. These studies indicate
      that the enone of the parent compound is not the only functional electrophile in
      curcumin, and that its oxidation products provide additional electrophilic sites.
      This suggests that protein binding by curcumin may involve oxidative activation
      into reactive quinone methide and spiroepoxide electrophiles.

PMID- 29569910
TI  - Rational Design of Dimeric Lysine N-Alkylamides as Potent and Broad-Spectrum
      Antibacterial Agents.
AB  - Antibiotic resistance is one of the biggest threats to public health, and new
      antibacterial agents hence are in an urgent need to combat infectious diseases
      caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy,
      we rationally designed and efficiently synthesized a new series of small molecule
      dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against
      a panel of Gram-positive and Gram-negative bacteria including MDR strains was
      performed, and a broad-spectrum and potent compound 3d was identified. This
      compound displayed high specificity toward bacteria over mammalian cell. Time
      kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated
      bacteria in a bactericidal mode by disrupting bacterial cell membrane. In
      addition, lead compound 3d could inhibit biofilm formation and did not develop
      drug resistance in S. aureus and E. coli over 14 passages. These results
      suggested that dimeric lysine nonylamide has immense potential as a new type of
      novel small molecular agent to combat antibiotic resistance.

PMID- 29569911
TI  - Role of Glucuronidation and P450 Oxidation in the Bioactivation of Bromfenac.
AB  - Bromfenac is a nonsteroidal anti-inflammatory drug that was approved in the
      United States in 1997. It was withdrawn from clinical use less than one year
      later, in 1998, due to hepatotoxicity. We investigate the potential of bromfenac
      to be metabolized to reactive intermediates to further the current understanding
      of bromfenac bioactivation. Incubations were conducted with hepatocytes and
      human, rat, and cynomolgus liver microsomes fortified with cofactors and N
      acetylcysteine. One thioether adduct of hydroxylated bromfenac and three
      thioether adducts of hydroxylated bromfenac indolinone were detected in extracts
      following incubations in liver microsomes fortified with NADPH and UDPGA. These
      findings demonstrate a bioactivation pathway for bromfenac and contribute to the
      body of evidence that could advance the understanding of the toxicity associated
      with bromfenac.

PMID- 29569912
TI  - Free Radical Production and Oxidative Stress in Lung Tissue of Patients Exposed
      to Sulfur Mustard: An Overview of Cellular and Molecular Mechanisms.
AB  - Sulfur mustard (SM) is a chemical alkylating compound that primary targets lung
      tissue. It causes a wide variety of pathological effects in respiratory system
      such as chronic bronchitis, bronchiolitis obliterans, necrosis of the mucosa and
      inflammation, chronic obstructive pulmonary disease (COPD), and pulmonary
      fibrosis. However, molecular and cellular mechanisms for these pathologies are
      still unclear. Oxidative stress (OS) induced by reactive oxygen species (ROS) is
      likely a significant mechanism by which SM leads to cell death and tissues
      injury. SM can trigger various molecular and cellular pathways that are linked to
      ROS generation, OS, and inflammation. Hypoxia-induced oxidative stress, reduced
      activity of enzymatic antioxidants, depletion of intercellular glutathione (GSH),
      decreased productivity of GSH-dependent antioxidants, mitochondrial dysfunction,
      accumulation of leukocytes and proinflammatory cytokines, and increased
      expression of ROS producing-related enzymes and inflammatory mediators are the
      major events in which SM leads to massive production of ROS and OS in pulmonary
      system. Therefore, understanding of these molecules and signaling pathways gives
      us valuable information about toxicological effects of SM on injured tissues and
      the way for developing a suitable clinical treatment. In this review, we aim to
      discuss the possible mechanisms by which SM induces excessive production of ROS,
      OS, and antioxidants depletion in lung tissue of exposed patients.

PMID- 29569913
TI  - Development of Polyclonal Antibodies for Detection of Diosbulbin B-Derived cis
      Enedial Protein Adducts.
AB  - Diosbulbin B (DSB), a major component of herbal medicine Dioscorea bulbifera L.
      (DB), can be metabolized to an electrophilic intermediate, DSB-derived cis
      enedial (DDE). DDE was suggested to contribute to the hepatotoxicity observed in
      experimental animals and humans after their exposure to DSB. Our previous work
      found that DDE reacted with primary amino and/or sulfhydryl groups of hepatic
      protein. The objective of the study was to develop polyclonal antibodies that can
      recognize DDE-derived protein adducts. Immunogens synthesized from DDE and
      keyhole limpet hemocyanin were employed to raise polyclonal antibodies in
      rabbits. An enzyme-linked immunosorbent assay (ELISA) demonstrated high titers of
      antisera obtained from immunized rabbits. Immunoblot analysis showed that DDE
      modified bovine serum albumin (BSA) was recognized by the obtained polyclonal
      antibodies in a concentration-dependent manner and without cross-reaction to
      native BSA. Competitive ELISA and competitive immunoblot analyses defined the
      specificity of the antibodies to recognize BSA modified by DDE. Immunoblot
      analysis also detected a multitude of chemiluminescent bands with a variety of
      molecular weights in liver homogenates that were harvested from mice treated with
      DSB. In summary, we have successfully raised polyclonal antibodies to detect
      protein adducts derived from DDE.

PMID- 29569914
TI  - Correction to "Unraveling the Correlations between Conformation, Lubrication, and
      Chemical Stability of Bottlebrush Polymers at Interfaces".

PMID- 29569915
TI  - Molecular Facts on the Structure and Dynamics of Electrolyte Species in Cu-Cl
      Cycle for Hydrogen Generation: An Insight from Molecular Dynamic Simulations.
AB  - The Cu complex, which is the key chemical species in well-known Cu-Cl hybrid
      thermochemical cycles and also in numerous metal hydrometallurgical and
      sedimentary deposit processes, displays a wide variety of structural and
      dynamical characteristics that are further complicated by the presence of
      multiple oxidation states of Cu ions with different coordination chemistries,
      therefore they are difficult to explore from experiments alone. In this article,
      an attempt has been made to understand the coordination behavior of the Cu
      complex using MD simulations. The study provides compelling evidence of the
      experimentally observed multiple stoichiometries of Cu ions, i.e., 1:6:0, 1:5:1,
      and 1:4:2 for Cu+:H2O:Cl- and 1:6:0 for Cu2+:H2O:Cl-. The presence of the anionic
      Cu complex, [Cu+Cl2]-.2H2O, [Cu+Cl2]-.3H2O, [Cu2+Cl3]-.H2O, and [Cu2+Cl3]-.2H2O,
      was captured in the presence of excess chloride ions. Furthermore, the
      probability distribution profiles have been estimated to determine the most
      possible complex in the considered systems. The results establish structural and
      dynamical reformation of the Cu complex with change in the salt concentration or
      variation in the solvent medium in which they are dissolved. Moreover, the
      structure and kinetics of the Cu ions in the Cu-Cl electrolyzer have been
      explored over a large range of the electric field by extending the simulated
      systems for varied strengths of the electric fields. It has been observed that
      with an increase in the strength of the electric field, the water molecules lose
      their coordination strength with central Cu ions, which, on the other hand,
      results in a significant change in the structure of the captured complex. The
      diffusion dynamics of the ions is altered while applying the electric field,
      which is furthermore modified while increasing the strength of electric field
      beyond a critical limit. In fact, the diffusion mechanism of the ions was seen to
      be transformed from Brownian-like to linear motion and then to hopping diffusion
      with the increasing strength of the electric field. To the best of our knowledge,
      this is the first time when the multiple oxidation states of the Cu ion are
      explored using MD simulations, and the coexisting pictures of the multiple
      coordinations and the solvent effects have been clearly revealed. Also to date,
      the present article is the first one to report the insights of the structure and
      the dynamics of the ions in the Cu-Cl electrolyzer over a wide range of the
      electric field. The present studies will be very helpful in understanding the
      mechanism involved in numerous metal hydrometallurgical and sedimentary deposit
      processes and to comprehend the analogies involved in the electrode reactions of
      the Cu-Cl cycle for hydrogen generation.

PMID- 29569916
TI  - Mechanistic Exploration of the Competition Relationship between a Ketone and C?C,
      C?N, or C?S Bond in the Rh(III)-Catalyzed Carbocyclization Reactions.
AB  - The introduction of a C?O, C?C, C?S, or C?N bond has emerged as an effective
      strategy for carbocycle synthesis. A computational mechanistic study of Rh(III)
      catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or alpha
      carbonyl-nitrones was carried out. Our results uncover the roles of dual
      directing groups in the three substrates and confirm that the ketone acts as the
      role of the directing group while the C?C, C?N, or C?S bond serves as the
      cyclization site. By comparing the coordination of the ketone versus the C?C,
      C?N, or C?S bond, as well as the chemoselectivity concerning the six- versus five
      membered formation, a competition relationship is revealed within the dual
      directing groups. Furthermore, after the alkyne insertion, instead of the
      originally proposed direct reductive elimination mechanism, the ketone
      enolization is found to be essential prior to the reductive elimination. The
      following C(sp2)-C(sp2) reductive elimination is more favorable than the C(sp3)
      C(sp2) formation, which can be explained by the aromaticity difference in the
      corresponding transition states. The substituent effect on controlling the
      selectivity was also discussed.

PMID- 29569917
TI  - Terminal Sugar Moiety Determines Immunomodulatory Properties of
      Poly(propyleneimine) Glycodendrimers.
AB  - Poly(propyleneimine) dendrimers fully surface-modified with disaccharide moieties
      (maltose, cellobiose, and lactose) designed to mimic natural lectin receptor
      ligands were tested for their bioactivity in two myeloid cell lines: THP-1 and HL
      60. Depending on the sugar modification, we observed variable activation of NF
      kappaB, AP-1, and NF-AT signaling pathways: lactose-coated dendrimers had the
      strongest impact on marker gene expression and most signaling events with the
      notable exception of NF-kappaB activation in THP-1 cells. The two cell lines
      showed an overall similar pattern of transcription factor and gene expression
      activation upon treatment with glycodendrimers, suggesting the involvement of
      galectin and C-type lectin receptor types. An important result of this action was
      the overexpression of CD40 and IL8 genes, potentially leading to an activated,
      proinflammatory phenotype in the monocyte/macrophage cell lineage. These
      pharmacodynamic characteristics of glycodendrimers need to be taken into account
      during their pharmaceutical applications both in drug delivery and direct
      immunomodulation.

PMID- 29569918
TI  - Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O
      Glycans.
AB  - Profiling specific glycans in histopathological samples is hampered by the lack
      of selective and sensitive tools for their detection. Here, we report on the
      development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based
      methods for the detection of O- and N-linked glycans on tissue sections via the
      use of sialyltransferases ST3Gal1 and ST6Gal1, respectively. Combining these two
      methods, we developed tandem labeling and double labeling strategies that permit
      the detection of unsialylated and sialylated glycans or the detection of O- and N
      linked glycans on the same tissue section, respectively. We applied these methods
      to screen murine tissue specimens, human multiple-organ cancer arrays, and
      lymphoma and prostate cancer arrays. Using tandem labeling with ST6Gal1 to
      analyze N-glycans in a prostate cancer array, we found striking differences in
      expression patterns of both sialylated and unsialylated N-glycans between
      cancerous and healthy samples. Such differences were also observed between normal
      tissue from healthy donors and healthy tissue adjacent to tumors. Our double
      labeling technique identified significant differences in unsialylated O-glycans
      between B-cell and T-cell lymphomas and between B-cell lymphomas and normal
      adjacent lymph nodes. Remarkable differences were also detected between adjacent
      lymph nodes and spleen tissue samples. These new chemoenzymatic histology methods
      therefore provide valuable tools for the analysis of glycans in clinically
      relevant tissue samples.

PMID- 29569919
TI  - Carbon Nitride Nanothread Crystals Derived from Pyridine.
AB  - Carbon nanothreads are a new one-dimensional sp3 carbon nanomaterial. They
      assemble into hexagonal crystals in a room temperature, nontopochemical solid
      state reaction induced by slow compression of benzene to 23 GPa. Here we show
      that pyridine also reacts under compression to form a well-ordered sp3 product:
      C5NH5 carbon nitride nanothreads. Solid pyridine has a different crystal
      structure from solid benzene, so the nontopochemical formation of low-dimensional
      crystalline solids by slow compression of small aromatics may be a general
      phenomenon that enables chemical design of properties. The nitrogen in the carbon
      nitride nanothreads may improve processability, alters photoluminescence, and is
      predicted to reduce the bandgap.

PMID- 29569920
TI  - Molecular Insights into Arctic Soil Organic Matter Degradation under Warming.
AB  - Molecular composition of the Arctic soil organic carbon (SOC) and its
      susceptibility to microbial degradation are uncertain due to heterogeneity and
      unknown SOC compositions. Using ultrahigh-resolution mass spectrometry, we
      determined the susceptibility and compositional changes of extractable dissolved
      organic matter (EDOM) in an anoxic warming incubation experiment (up to 122 days)
      with a tundra soil from Alaska (United States). EDOM was extracted with 10 mM
      NH4HCO3 from both the organic- and mineral-layer soils during incubation at both 
      2 and 8  degrees C. Based on their O:C and H:C ratios, EDOM molecular formulas
      were qualitatively grouped into nine biochemical classes of compounds, among
      which lignin-like compounds dominated both the organic and the mineral soils and
      were the most stable, whereas amino sugars, peptides, and carbohydrate-like
      compounds were the most biologically labile. These results corresponded with
      shifts in EDOM elemental composition in which the ratios of O:C and N:C
      decreased, while the average C content in EDOM, molecular mass, and aromaticity
      increased after 122 days of incubation. This research demonstrates that certain
      EDOM components, such as amino sugars, peptides, and carbohydrate-like compounds,
      are disproportionately more susceptible to microbial degradation than others in
      the soil, and these results should be considered in SOC degradation models to
      improve predictions of Arctic climate feedbacks.

PMID- 29569921
TI  - Computational Study of the Structure and Degradation Products of Alloxydim
      Herbicide.
AB  - Density functional theory calculations allowed us to study alloxydim herbicide
      and to identify the most stable conformers, the factors that governs their
      stability, and the interconversion mechanisms among the most relevant conformers.
      The degradation chain involves, as a first step, the cleavage of the N-O bond and
      the formation of a stable intermediate difficult to characterize experimentally.
      The study performed also allowed us to identify the properties of this elusive
      intermediate and to determine that the dominant fragmentation process in the gas
      phase is the homolytic fragmentation. Stability of alloxydim conformers and
      homolytic fragments were also assessed in the water phase. Computed IR spectra
      were consistent with those observed experimentally.

PMID- 29569922
TI  - Melting of the Au20 Gold Cluster: Does Charge Matter?
AB  - We investigate the dependence upon the charge of the heat capacities of magic
      gold cluster Au20 obtained from density functional-based tight binding theory
      within parallel tempering molecular dynamics and the multiple histogram method.
      The melting temperatures, determined from the heat capacity curves, are found to
      be 1102 K for neutral Au20 and only 866 and 826 K for Au20+ and Au20-. Both the
      canonical and the microcanonical aspects of the transition are discussed. A
      convex intruder, associated with a negative heat capacity, is evidenced in the
      microcanonical entropy in the case of the neutral cluster but is absent in the
      melting processes of the ions. The present work shows that a single charge
      quantitatively affects the thermal properties of the gold 20mer.

PMID- 29569923
TI  - Correlation between Gas Bubble Formation and Hydrogen Evolution Reaction Kinetics
      at Nanoelectrodes.
AB  - We report the correlation between H2 gas bubble formation potential and hydrogen
      evolution reaction (HER) activity for Au and Pt nanodisk electrodes (NEs).
      Microkinetic models were formulated to obtain the HER kinetic information for
      individual Au and Pt NEs. We found that the rate-determining steps for the HER at
      Au and Pt NEs were the Volmer step and the Heyrovsky step, respectively. More
      interestingly, the standard rate constant ( k0) of the rate-determining step was
      found to vary over 2 orders of magnitude for the same type of NEs. The observed
      variations indicate the HER activity heterogeneity at the nanoscale. Furthermore,
      we discovered a linear relationship between bubble formation potential ( Ebubble)
      and log( k0) with a slope of 125 mV/decade for both Au and Pt NEs. As log ( k0)
      increases, Ebubble shifts linearly to more positive potentials, meaning NEs with
      higher HER activities form H2 bubbles at less negative potentials. Our
      theoretical model suggests that such linear relationship is caused by the similar
      critical bubble formation condition for Au and Pt NEs with varied sizes. Our
      results have potential implications for using gas bubble formation to evaluate
      the HER activity distribution of nanoparticles in an ensemble.

PMID- 29569924
TI  - Femtosecond Dynamics of Photoexcited C60 Films.
AB  - The well known organic semiconductor C60 is attracting renewed attention due to
      its centimeter-long electron diffusion length and high performance of solar cells
      containing 95% fullerene, yet its photophysical properties remain poorly
      understood. We elucidate the dynamics of Frenkel and intermolecular (inter-C60)
      charge-transfer (CT) excitons in neat and diluted C60 films from high-quality
      femtosecond transient absorption (TA) measurements performed at low fluences and
      free from oxygen or pump-induced photodimerization. We find from preferential
      excitation of either species that the CT excitons give rise to a strong electro
      absorption (EA) signal but are extremely short-lived. The Frenkel exciton
      relaxation and triplet yield strongly depend on the C60 aggregation. Finally, TA
      measurements on full devices with applied electric field allow us to optically
      monitor the dissociation of CT excitons into free charges for the first time and
      to demonstrate the influence of cluster size on the spectral signature of the C60
      anion.

PMID- 29569925
TI  - Toward a Ferrous Iron-Cleavable Linker for Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADCs) are antigen-targeted therapeutics that employ
      antibodies to deliver potent, cytotoxic effectors to cells with potentially high
      specificity. While promising clinical results have been achieved, significant
      pitfalls remain including internalization of ADCs in nontargeted cells expressing
      target antigen, which can limit therapeutic windows. Novel ADC linkers that are
      cleaved selectively in cancer cells but not in normal cells could minimize
      collateral damage caused by ADC uptake in nontargeted tissues. Here, we describe
      a prototypical ADC linker based on an Fe(II)-reactive 1,2,4-trioxolane scaffold
      (TRX) that by itself has demonstrated tumor-selective activity in preclinical
      cancer models. We prepared TRX-linked ADCs by site-selective conjugation to two
      sites in trastuzumab and compared their activity in Her2 positive and negative
      cells to ADC controls based on established linker chemistry. Our results confirm
      that the TRX moiety efficiently releases its payload following ADC uptake,
      affording picomolar potencies in antigen-positive cells. We also identified a
      destabilizing interaction between these initial TRX linkers and nearby antibody
      residues and suggest an approach to improve upon these prototypical designs.

PMID- 29569926
TI  - Intracellular Delivery of Nanomaterials via an Inertial Microfluidic Cell
      Hydroporator.
AB  - The introduction of nanomaterials into cells is an indispensable process for
      studies ranging from basic biology to clinical applications. To deliver foreign
      nanomaterials into living cells, traditionally endocytosis, viral and lipid
      nanocarriers or electroporation are mainly employed; however, they critically
      suffer from toxicity, inconsistent delivery, and low throughput and are time
      consuming and labor-intensive processes. Here, we present a novel inertial
      microfluidic cell hydroporator capable of delivering a wide range of
      nanomaterials to various cell types in a single-step without the aid of carriers
      or external apparatus. The platform inertially focuses cells into the channel
      center and guides cells to collide at a T-junction. Controlled compression and
      shear forces generate transient membrane discontinuities that facilitate passive
      diffusion of external nanomaterials into the cell cytoplasm while maintaining
      high cell viability. This hydroporation method shows superior delivery
      efficiency, is high-throughput, and has high controllability; moreover, its
      extremely simple and low-cost operation provides a powerful and practical
      strategy in the applications of cellular imaging, biomanufacturing, cell-based
      therapies, regenerative medicine, and disease diagnosis.

PMID- 29569927
TI  - Molecular Origin of Photoprotection in Cyanobacteria Probed by Watermarked
      Femtosecond Stimulated Raman Spectroscopy.
AB  - Photoprotection is fundamental in photosynthesis to avoid oxidative photodamage
      upon excess light exposure. Excited chlorophylls (Chl) are quenched by
      carotenoids, but the precise molecular origin remains controversial. The
      cyanobacterial HliC protein belongs to the Hlip family ancestral to plant light
      harvesting complexes, and binds Chl a and beta-carotene in 2:1 ratio. We analyzed
      HliC by watermarked femtosecond stimulated Raman spectroscopy to follow the time
      evolution of its vibrational modes. We observed a 2 ps rise of the C?C stretch
      band of the 2Ag- (S1) state of beta-carotene upon Chl a excitation, demonstrating
      energy transfer quenching and fast excess-energy dissipation. We detected two
      distinct beta-carotene conformers by the C?C stretch frequency of the 2Ag- (S1)
      state, but only the beta-carotene whose 2Ag- energy level is significantly
      lowered and has a lower C?C stretch frequency is involved in quenching. It
      implies that the low carotenoid S1 energy that results from specific pigment
      protein or pigment-pigment interactions is the key property for creating a
      dissipative energy channel. We conclude that watermarked femtosecond stimulated
      Raman spectroscopy constitutes a promising experimental method to assess energy
      transfer and quenching mechanisms in oxygenic photosynthesis.

PMID- 29569928
TI  - Exciton-Dominated Core-Level Absorption Spectra of Hybrid Organic-Inorganic Lead
      Halide Perovskites.
AB  - In a combined theoretical and experimental work, we investigate X-ray absorption
      near-edge structure spectroscopy of the I L3 and the Pb M5 edges of the
      methylammonium lead iodide (MAPbI3) hybrid inorganic-organic perovskite and its
      binary phase PbI2. The absorption onsets are dominated by bound excitons with
      sizable binding energies of a few hundred millielectronvolts and pronounced
      anisotropy. The spectra of both materials exhibit remarkable similarities,
      suggesting that the fingerprints of core excitations in MAPbI3 are essentially
      given by its inorganic component, with negligible influence from the organic
      groups. The theoretical analysis complementing experimental observations provides
      the conceptual insights required for a full characterization of this complex
      material.

PMID- 29569929
TI  - An Isolable and Bench-Stable Epoxidizing Reagent Based on Triazine: Triazox.
AB  - A new triazine-based oxidizing reagent, 2-hydroperoxy-4,6-diphenyl-1,3,5-triazine
      (Triazox), has been developed. The reagent can be synthesized from inexpensive
      starting materials and is a bench-stable solid that is isolable in pure form.
      Epoxidation of alkenes possessing acid-sensitive functionalities using Triazox
      proceeded in good to excellent yields. The accompanying nonacidic triazinone
      coproduct can be easily removed by filtration. These features indicate that
      Triazox is a practically useful oxidizing reagent.

PMID- 29569930
TI  - Double Barrel Nanopores as a New Tool for Controlling Single-Molecule Transport.
AB  - The ability to control the motion of single biomolecules is key to improving a
      wide range of biophysical and diagnostic applications. Solid-state nanopores are
      a promising tool capable of solving this task. However, molecular control and the
      possibility of slow readouts of long polymer molecules are still limited due to
      fast analyte transport and low signal-to-noise ratios. Here, we report on a novel
      approach of actively controlling analyte transport by using a double-nanopore
      architecture where two nanopores are separated by only a ~ 20 nm gap. The
      nanopores can be addressed individually, allowing for two unique modes of
      operation: (i) pore-to-pore transfer, which can be controlled at near 100%
      efficiency, and (ii) DNA molecules bridging between the two nanopores, which
      enables detection with an enhanced temporal resolution (e.g., an increase of more
      than 2 orders of magnitude in the dwell time) without compromising the signal
      quality. The simplicity of fabrication and operation of the double-barrel
      architecture opens a wide range of applications for high-resolution readout of
      biological molecules.

PMID- 29569931
TI  - A Synthetic Route to Sodium alpha-Aminoalkanesulfinates and Their Application in
      the Generation of alpha-Aminoalkyl Radicals for Radical Addition Reactions.
AB  - The synthesis of sodium alpha-aminoalkanesulfinates and their synthetic utility
      as alpha-aminoalkyl radical precursors are reported. A variety of alpha
      aminoalkanesulfinates were readily obtained from the reaction between the anions
      of N-Boc-protected alkylamines and 1,4-diazabicyclo[2.2.2]octanebis(sulfur
      dioxide). Treatment of sodium alpha-aminoalkanesulfinates with
      (diacetoxyiodo)benzene easily generated the corresponding alpha-aminoalkyl
      radicals under mild conditions, which were then applied in radical 1,2-addition
      to imines, radical 1,4-addition to electron-deficient olefins, and radical
      addition/cyclization to 2-isocyanobiphenyls.

PMID- 29569932
TI  - Aryne Trifunctionalization Enabled by 3-Silylaryne as a 1,2-Benzdiyne Equivalent.
AB  - An unprecedented aryne 1,2,3-trifunctionalization protocol from 2,6
      bis(silyl)aryl triflates was developed under transition-metal-free conditions.
      The reaction of generated 3-silylaryne with both pyridine N-oxide and N
      hydroxylamide afforded o-silyl triflate/tosylate in a one-pot transformation,
      allowing the formation of 2,3-aryne precursors with various vicinal
      pyridinyl/amido substituents. These pyridinyl-substituted 2,3-aryne intermediates
      exhibit a broad scope of reactivity with diverse arynophiles in good yields and
      high selectivity.

PMID- 29569933
TI  - Thoracic-abdominal imaging with a novel dual-layer spectral detector CT: intra
      individual comparison of image quality and radiation dose with 128-row single
      energy acquisition.
AB  - BACKGROUND: A novel, multi-energy, dual-layer spectral detector computed
      tomography (SDCT) is commercially available now with the vendor's claim that it
      yields the same or better quality of polychromatic, conventional CT images like
      modern single-energy CT scanners without any radiation dose penalty. PURPOSE: To
      intra-individually compare the quality of conventional polychromatic CT images
      acquired with a dual-layer spectral detector (SDCT) and the latest generation 128
      row single-energy-detector (CT128) from the same manufacturer. MATERIAL AND
      METHODS: Fifty patients underwent portal-venous phase, thoracic-abdominal CT
      scans with the SDCT and prior CT128 imaging. The SDCT scanning protocol was
      adapted to yield a similar estimated dose length product (DLP) as the CT128.
      Patient dose optimization by automatic tube current modulation and CT image
      reconstruction with a state-of-the-art iterative algorithm were identical on both
      scanners. CT image contrast-to-noise ratio (CNR) was compared between the SDCT
      and CT128 in different anatomic structures. Image quality and noise were assessed
      independently by two readers with 5-point-Likert-scales. Volume CT dose index
      (CTDIvol), and DLP were recorded and normalized to 68 cm acquisition length
      (DLP68). RESULTS: The SDCT yielded higher mean CNR values of 30.0% +/- 2.0% (26.4
      32.5%) in all anatomic structures ( P < 0.001) and excellent scores for
      qualitative parameters surpassing the CT128 (all P < 0.0001) with substantial
      inter-rater agreement (kappa >= 0.801). Despite adapted scan protocols the SDCT
      yielded lower values for CTDIvol (-10.1 +/- 12.8%), DLP (-13.1 +/- 13.9%), and
      DLP68 (-15.3 +/- 16.9%) than the CT128 (all P < 0.0001). CONCLUSION: The SDCT
      scanner yielded better CT image quality compared to the CT128 and lower radiation
      dose parameters.

PMID- 29569935
TI  - Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through
      combatting oxidative damage.
AB  - Doxorubicin (DOX) is an effective anticancer drug which is widely used in
      clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it
      is an urgent need to attenuate the toxicity of DOX without impairing its
      efficacy. Many studies show that Se may protect normal tissues from damages of
      some anticancer drugs. Recently, Se@SiO2 nanocomposites emerges as better
      substitutes for direct element Se in treatment of cancer cells for their ideal
      biocompatibility. In the present article, we synthesized Se@SiO2 nanocomposites
      and confirmed their characterization according to previous studies. We
      accomplished a conjunctive use of Se@SiO2 nanocomposites with DOX then explored
      the toxicity and efficacy of this combination. In the in vivo experiments, the
      survival rate of mice with DOX treatment was significantly increased by Se@SiO2.
      And Se@SiO2 has few interference to the therapeutic effect of DOX. Particularly,
      Se@SiO2 significantly attenuated DOX-induced myocardial tissue damage (serum
      index, apoptosis index, western-blot index) and protected mice from reduction in
      LVEF induced by DOX in mice model. In summary, we concluded that the protective
      effect of Se@SiO2 in DOX-induced cardiotoxicity was possibly attributable to the
      inhibition of ROS production, showing great potential of Se@SiO2 nanocomposite in
      the clinical use of DOX.

PMID- 29569934
TI  - Intergenic and intronic DNA hypomethylated regions as putative regulators of
      imprinted domains.
AB  - AIM: To investigate the regulatory potential of intergenic/intronic
      hypomethylated regions (iHMRs) within imprinted domains. MATERIALS & METHODS:
      Based on the preliminary results of the histone modification and conservation
      profiles, we conducted reporter assays on the Peg3 and H19 domain iHMRs. The in
      vitro results were confirmed by the in vivo deletion of Peg3-iHMR designed to
      test its function in the Peg3 imprinted domain. RESULTS & CONCLUSION: Initial
      bioinformatic analyses suggested that some iHMRs may be noncanonical enhancers
      for imprinted genes. Consistent with this, Peg3- and H19-iHMRs showed context
      dependent promoter and enhancer activity. Further, deletion of Peg3-iHMR resulted
      in allele- and sex-specific misregulation of several imprinted genes within the
      domain. Taken together, these results suggest that some iHMRs may function as
      domain-wide regulators for the associated imprinted domains.

PMID- 29569936
TI  - Target discovery focused approaches to overcome bottlenecks in the exploitation
      of antimycobacterial natural products.
AB  - Tuberculosis is a major global health hazard. The search for new
      antimycobacterials has focused on such as screening combinational chemistry
      libraries or designing chemicals to target predefined pockets of essential
      bacterial proteins. The relative ineffectiveness of these has led to a
      reappraisal of natural products for new antimycobacterial drug leads. However,
      progress has been limited, we suggest through a failure in many cases to define
      the drug target and optimize the hits using this information. We highlight
      methods of target discovery needed to develop a drug into a candidate for
      clinical trials. We incorporate these into suggested analysis pipelines which
      could inform the research strategies to accelerate the development of new drug
      leads from natural products.

PMID- 29569937
TI  - The role of microRNAs and nanoparticles in ovarian cancer: a review.
AB  - MicroRNAs (miRNAs) have had a revolutionary impact on cancer research over the
      recent years. They emerge as important players in tumourigenesis, leading to a
      paradigm shift in oncology. Ovarian cancer is the leading cause of death among
      gynaecologic malignancies. Therefore, there is a strong need for prognostic and
      predictive markers for early diagnosis which helps optimize and personalize
      treatment. Asymptomatically, ovarian cancer is often diagnosed at advanced and
      incurable stages. Efficient targeting and sustained release of miRNAs/anti-miRNAs
      using nanoparticles conjugated with antibodies and/or peptides could reduce the
      required therapeutic dosage while minimizing systemic and cellular toxicity.
      Given miRNAs importance in clinical oncology, here we focus on the development of
      miRNA nanoformulations to achieve enhanced cellular uptake, bioavailability and
      accumulation at the tumour site. Although many obstacles need to be overcome,
      miRNA therapy could be a powerful tool for ovarian cancer prevention and
      treatment. In this review, we discuss about the emerging roles of miRNAs in
      various aspects of ovarian cancer.

PMID- 29569938
TI  - New opportunities for GPCR allosteric modulators.

PMID- 29569939
TI  - Ranking of the most effective treatments for cardiovascular disease using SUCRA:
      Is it as sweet as it appears?

PMID- 29569940
TI  - mHealth and cardiovascular diseases self-management: There is still a long way
      ahead of us.

PMID- 29569942
TI  - Balance and Coordination Proficiency of Age-Matched Male and Female Children and
      Adolescents With Intellectual Disabilities.
AB  - Male youth (8-18 years) with intellectual disability (ID) demonstrate motor
      proficiency below age-related competence capacities for typically developing
      youth. Whether below-criteria motor proficiency also exists for females with ID
      is not known. The purpose of this study was to determine if sex-specific
      differences exist in motor proficiency for youth with ID. The Bruininks-Oseretsky
      Test of Motor Proficiency was used to measure motor proficiency: six items for
      upper limb coordination, seven items for balance, and six items for bilateral
      coordination. One hundred and seventy-two (172) males and 85 females with ID but
      without Down syndrome were divided into five age groups for comparative purposes:
      8-10, 11-12, 13-14, 15-16, and 17-21 years. Males scored sufficiently higher than
      females to suggest that sex data should not be combined to established Bruininks
      Oseretsky Test of Motor Proficiency standards for upper limb coordination,
      balance, and bilateral coordination subtests.

PMID- 29569941
TI  - Complexities of post-transcriptional regulation and the modeling of ceRNA
      crosstalk.
AB  - Control of gene and protein expression is required for cellular homeostasis and
      is disrupted in disease. Following transcription, mRNA turnover and translation
      is modulated, most notably by microRNAs (miRNAs). This modulation is controlled
      by transcriptional and post-transcriptional events that alter the availability of
      miRNAs for target binding. Recent studies have proposed that some transcripts -
      termed competitive endogenous RNAs (ceRNAs) - sequester a miRNA and diminish its
      repressive effects on other transcripts. Such ceRNAs thus mutually alter each
      other's abundance by competing for binding to a common set of miRNAs. Some
      question the relevance of ceRNA crosstalk, arguing that an individual transcript,
      when its abundance lies within a physiological range of gene expression, will
      fail to compete for miRNA binding due to the high abundance of other miRNA
      binding sites across the transcriptome. Despite this, some experimental evidence
      is consistent with the ceRNA hypothesis. In this review, we draw upon existing
      data to highlight mechanistic and theoretical aspects of ceRNA crosstalk. Our
      intent is to propose how understanding of ceRNA crosstalk mechanisms can be
      improved and what evidence is required to demonstrate a ceRNA mechanism. A
      greater understanding of factors affecting ceRNA crosstalk should shed light on
      its relevance in physiological states.

PMID- 29569943
TI  - Whole-Body-Vibration Training and Balance in Recreational Athletes With Chronic
      Ankle Instability.
AB  - CONTEXT:   Deficits in the propioceptive system of the ankle contribute to
      chronic ankle instability (CAI). Recently, whole-body-vibration (WBV) training
      has been introduced as a preventive and rehabilitative tool. OBJECTIVE:   To
      evaluate how a 6-week WBV training program on an unstable surface affected
      balance and body composition in recreational athletes with CAI. DESIGN:  
      Randomized controlled clinical trial. SETTING:   Research laboratory. PATIENTS OR
      OTHER PARTICIPANTS:   Fifty recreational athletes with self-reported CAI were
      randomly assigned to a vibration (VIB), nonvibration (NVIB), or control group.
      INTERVENTION(S):   The VIB and NVIB groups performed unilateral balance training
      on a BOSU 3 times weekly for 6 weeks. The VIB group trained on a vibration
      platform, and the NVIB group trained on the floor. MAIN OUTCOME MEASURE(S):   We
      assessed balance using the Biodex Balance System and the Star Excursion Balance
      Test (SEBT). Body composition was measured by dual-energy x-ray absorptiometry.
      RESULTS:   After 6 weeks of training, improvements on the Biodex Balance System
      occurred only on the Overall Stability Index ( P = .01) and Anterior-Posterior
      Stability Index ( P = .03) in the VIB group. We observed better performance in
      the medial ( P = .008) and posterolateral ( P = .04) directions and composite
      score of the SEBT in the VIB group ( P = .01) and in the medial ( P < .001),
      posteromedial ( P = .002), and posterolateral ( P = .03) directions and composite
      score of the SEBT in the NVIB group ( P < .001). No changes in body composition
      were found for any of the groups. CONCLUSIONS:   Only the VIB group showed
      improvements on the Biodex Balance System, whereas the VIB and NVIB groups
      displayed better performance on the SEBT.

PMID- 29569944
TI  - Shoulder Taping and Neuromuscular Control.
AB  - CONTEXT:   Scapular taping can offer clinical benefit to some patients with
      shoulder pain; however, the underlying mechanisms are unclear. Understanding
      these mechanisms may guide the development of treatment strategies for managing
      neuromusculoskeletal shoulder conditions. OBJECTIVE:   To examine the mechanisms
      underpinning the benefits of scapular taping. DESIGN:   Descriptive laboratory
      study. SETTING:   University laboratory. PATIENTS OR OTHER PARTICIPANTS:   A
      total of 15 individuals (8 men, 7 women; age = 31.0 +/- 12.4 years, height =
      170.9 +/- 7.6 cm, mass = 73.8 +/- 14.4 kg) with no history of shoulder pain.
      INTERVENTION(S):   Scapular taping. MAIN OUTCOME MEASURE(S):   Surface
      electromyography (EMG) was used to assess the (1) magnitude and onset of
      contraction of the upper trapezius (UT), lower trapezius (LT), and serratus
      anterior relative to the contraction of the middle deltoid during active shoulder
      flexion and abduction and (2) corticomotor excitability (amplitude of motor
      evoked potentials from transcranial magnetic stimulation) of these muscles at
      rest and during isometric abduction. Active shoulder-flexion and shoulder
      abduction range of motion were also evaluated. All outcomes were measured before
      taping, immediately after taping, 24 hours after taping with the original tape
      on, and 24 hours after taping with the tape removed. RESULTS:   Onset of
      contractions occurred earlier immediately after taping than before taping during
      abduction for the UT (34.18 +/- 118.91 milliseconds and 93.95 +/- 106.33
      milliseconds, respectively, after middle deltoid contraction; P = .02) and during
      flexion for the LT (110.02 +/- 109.83 milliseconds and 5.94 +/- 92.35
      milliseconds, respectively, before middle deltoid contraction; P = .06). These
      changes were not maintained 24 hours after taping. Mean motor-evoked potential
      onset of the middle deltoid was earlier at 24 hours after taping (tape on = 7.20
      +/- 4.33 milliseconds) than before taping (8.71 +/- 5.24 milliseconds, P = .008).
      We observed no differences in peak root mean square EMG activity or corticomotor
      excitability of the scapular muscles among any time frames. CONCLUSIONS:  
      Scapular taping was associated with the earlier onset of UT and LT contractions
      during shoulder abduction and flexion, respectively. Altered corticomotor
      excitability did not underpin earlier EMG onsets of activity after taping in this
      sample. Our findings suggested that the optimal time to engage in rehabilitative
      exercises to facilitate onset of trapezius contractions during shoulder movements
      may be immediately after tape application.

PMID- 29569945
TI  - Four new C19-diterpenoid alkaloids from the roots of Aconitum ouvrardianum.
AB  - Four new C19-diterpenoid alkaloids, 3-dehydroxyl-lipoindaconitine (1), 8
      dehydroxyl-bikhaconine (2), 19R-acetonyl-talatisamine (3), and 16-hydroxyl
      vilmorisine (4), were isolated from the roots of Aconitum ouvrardianum. Their
      structures were elucidated by spectral analyses, including ESI-MS, HR-ESI-MS, IR,
      UV, 1D and 2D NMR.

PMID- 29569946
TI  - Surface-Enhanced Raman Scattering (SERS) in Microbiology: Illumination and
      Enhancement of the Microbial World.
AB  - The microbial world forms a huge family of organisms that exhibit the greatest
      phylogenetic diversity on Earth and thus colonize virtually our entire planet.
      Due to this diversity and subsequent complex interactions, the vast majority of
      microorganisms are involved in innumerable natural bioprocesses and contribute an
      absolutely vital role toward the maintenance of life on Earth, whilst a small
      minority cause various infectious diseases. The ever-increasing demand for
      environmental monitoring, sustainable ecosystems, food security, and improved
      healthcare systems drives the continuous search for inexpensive but reproducible,
      automated and portable techniques for detection of microbial isolates and
      understanding their interactions for clinical, environmental, and industrial
      applications and benefits. Surface-enhanced Raman scattering (SERS) is attracting
      significant attention for the accurate identification, discrimination and
      characterization and functional assessment of microbial cells at the single cell
      level. In this review, we briefly discuss the technological advances in Raman and
      Fourier transform infrared (FT-IR) instrumentation and their application for the
      analysis of clinically and industrially relevant microorganisms, biofilms, and
      biological warfare agents. In addition, we summarize the current trends and
      future prospects of integrating Raman/SERS-isotopic labeling and cell sorting
      technologies in parallel, to link genotype-to-phenotype in order to define
      community function of unculturable microbial cells in mixed microbial communities
      which possess admirable traits such as detoxification of pollutants and recycling
      of essential metals.

PMID- 29569947
TI  - Tivanisiran, a novel siRNA for the treatment of dry eye disease.
AB  - INTRODUCTION: Dry eye disease (DED) is characterized by an alteration of the tear
      film with ocular inflammation and neurosensory abnormalities. The main clinical
      signs of this condition are tear instability and ocular damage. Although DED has
      gained significant attention in the past few years, limited prescription
      treatment options are available for patients. Areas covered: The current
      manuscript summarizes the pre-clinical and clinical development of tivanisiran, a
      novel small interfering oligonucleotide of RNA (siRNA) used for the treatment of
      DED. Tivanisiran was designed to silence Transient Receptor Potential Vanilloid 1
      (TRPV1); herein the chemistry and mechanism of action of this new compound is
      also described. Expert opinion: Drugs currently on the market mostly target the
      inflammatory component of the disease and show only partial efficacy. New
      compounds addressing other aspects of the disease would provide significant
      advantages and contribute to a more personalized treatment of the disease.
      Tivanisiran has been designed to reduce ocular discomfort and pain, and was shown
      to improve ocular hyperemia and tear quality in human and animal models.
      Consequently, if the results of the ongoing and future clinical trials meet their
      study endpoints, tivanisiran could be submitted to obtain approval for the
      treatment of DED.

PMID- 29569948
TI  - Targeting p53 as a promising therapeutic option for cancer by re-activating the
      wt or mutant p53's tumor suppression.
AB  - p53 protein, a product of the TP53 tumor suppressor gene, controls the cellular
      genome's integrity and is an important regulator of cell cycling, proliferation,
      apoptosis and metabolism. Mutations of TP53 or inactivation of its gene product
      are among the first events initiating malignant transformation. The consequent
      loss of control over the cell cycle, resulting in accelerated cell proliferation
      and facilitating metabolic reprogramming, gives the initiated (premalignant)
      cells numerous advantages over healthy cells. Interestingly, p53 status is not
      only an important marker in cancer diagnosis; it has also become a promising
      target of personalized therapy. Depending on the TP53 status different
      therapeutic options have been developed. (Re)-activation of p53 functionality in
      cancer cells offers promising new alternatives to existing oncological therapies.

PMID- 29569949
TI  - Altered expression of transcription factors IRF4 and IRF8 in peripheral blood B
      cells is associated with clinical severity and circulating plasma cells frequency
      in patients with myasthenia gravis.
AB  - Previous studies have shown that interferon regulatory factor-4 (IRF4) and IRF8
      play critical but distinct roles in the differentiation of B cells into plasma
      cells (PCs). In the present study, we aimed to measure the expression levels of
      IRF4 and IRF8 in B cells from patients with myasthenia gravis (MG) and to
      investigate whether the expression of IRF4 and IRF8 associates with pathogenesis
      of MG. A total of 35 anti-acetylcholine receptor (AChR) antibody (Ab)-positive
      patients with MG [20 generalized MG (GMG) and 15 ocular MG (OMG) and 25 healthy
      donors were recruited in this study. The quantitative myasthenia gravis score
      (QMGS) was used to evaluate the clinical severity. Real-time PCR and Western blot
      were used to measure the levels of IRF4 and IRF8 expressed in peripheral blood B
      cells. Peripheral blood CD138+ PCs were assayed by flow cytometry. Our data
      demonstrated that the mRNA/protein levels of IRF4 and IRF8 were significantly
      higher and lower, respectively, in patients with OMG/GMG groups compared with
      healthy controls. In addition, IRF4 expression was significantly higher and IRF8
      expression was significantly lower in GMG group than in OMG group. Pearson's
      correlation analysis revealed that IRF8 expression was negatively correlated with
      clinical severity, PCs frequency and anti-AChR Ab levels, while IRF4 expression
      and IRF4/IRF8 ratio was positively correlated with these parameters in two MG
      subgroups. Finally, glucocorticoid treatment can relieve the imbalance of
      IRF4/IRF8 in peripheral blood B cells, and this restoration is accompanied by
      reduced PCs frequency and clinical symptoms. These evidences suggest that IRF4
      and IRF8 are important in the counter-balancing mechanisms controlling
      differentiation of PCs in MG. The disruption of the balanced IRF4/IFR8 ratio in B
      cells may play important roles in the pathogenesis of MG and offer a promising
      therapeutic target for the development of novel immunotherapy for MG patients.

PMID- 29569950
TI  - Decision fatigue: A conceptual analysis.
AB  - Decision fatigue is an applicable concept to healthcare psychology. Due to a lack
      of conceptual clarity, we present a concept analysis of decision fatigue. A
      search of the term "decision fatigue" was conducted across seven research
      databases, which yielded 17 relevant articles. The authors identified three
      antecedent themes (decisional, self-regulatory, and situational) and three
      attributional themes (behavioral, cognitive, and physiological) of decision
      fatigue. However, the extant literature failed to adequately describe
      consequences of decision fatigue. This concept analysis provides needed
      conceptual clarity for decision fatigue, a concept possessing relevance to
      nursing and allied health sciences.

PMID- 29569951
TI  - A review of dexketoprofen trometamol in acute pain.
AB  - OBJECTIVE: Dexketoprofen trometamol is a modified non-selective COX inhibitor
      with a rapid onset of action that is available as both oral and parenteral
      formulations. The aim of this narrative review was to assess the efficacy and
      tolerability/safety of dexketoprofen trometamol in acute pain states using the
      best available published scientific evidence (randomized controlled clinical
      trials and systematic reviews/meta-analyses). METHODS: Literature retrieval was
      performed via Medline, Embase and the Cochrane Library (from inception up to
      March 2017) using combinations of the terms "randomized controlled trials",
      "dexketoprofen", "celecoxib", "etoricoxib", "parecoxib" and "acute pain".
      RESULTS: Single-dose dexketoprofen trometamol provides effective analgesia in the
      treatment of acute pain, such as postoperative pain (dental and non-dental
      surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and
      reduces opioid consumption in the postoperative setting. It has a rapid onset of
      action (within 30 minutes) and is well tolerated during short-term treatment.
      Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and
      tolerability of single-dose dexketoprofen trometamol appears to be consistent
      with that seen with celecoxib, etoricoxib and parecoxib in the acute pain
      setting. CONCLUSION: In conclusion, dexketoprofen trometamol appears to provide
      similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has
      a rapid onset of action, is well tolerated, and has an opioid-sparing effect when
      used as part of a multimodal regimen in the acute pain setting.

PMID- 29569953
TI  - The growing landscape of ictal epileptic headache.

PMID- 29569952
TI  - Strategies against methicillin-resistant Staphylococcus aureus persisters.
AB  - Chronic Staphylococcus aureus infections are complicated by frequent relapses not
      only from the development of drug resistance to conventional antibiotics, but
      also through the formation of persister bacterial cells. Bacterial persisters are
      in a transient, metabolically inactive state, making conventional antibiotics
      that target essential cellular growth processes ineffective, resulting in high
      clinical failure rates of antibiotic chemotherapy. The development of new
      antibiotics against persistent S. aureus is an urgent issue. Over the last
      decade, new strategies to identify S. aureus persister-active compounds have been
      proposed. This review summarizes the proposed targets, antipersister compounds
      and innovative methods that may augment conventional antibiotics against S.
      aureus persisters. The reviewed antipersister strategies can be summarized as two
      broad categories; directly targeting growth-independent targets and potentiating
      existing, ineffective antibiotics by aiding uptake or accessibility.

PMID- 29569954
TI  - Nitrosative stress uncovers potent beta2-adrenergic receptor-linked vasodilation
      further enhanced by blockade of clathrin endosome formation.
AB  - This study investigated the effect of sodium nitroprusside (SNP) preexposure on
      vasodilation via the beta-adrenergic receptor (BAR) system. SNP was used as a
      nitrosative/oxidative proinflammatory insult. Small arterioles were visualized by
      intravital microscopy in the hamster cheek pouch tissue (isoflurane, n = 45).
      Control dilation to isoproterenol (EC50: 10-7 mol/l) became biphasic as a
      function of concentration after 2 min of exposure to SNP (10-4 M), with increased
      potency at picomolar dilation uncovered and decreased efficacy at the micromolar
      dilation. Control dilation to curcumin was likewise altered after SNP, but only
      the increased potency at a low dose was uncovered, whereas micromolar dilation
      was eliminated. The picomolar dilations were blocked by the potent BAR-2 inverse
      agonist carazolol (10-9 mol/l). Dynamin inhibition with dynasore mimicked this
      effect, suggesting that SNP preexposure prevented BAR agonist internalization.
      Using HeLa cells transfected with BAR-2 tagged with monomeric red fluorescent
      protein, exposure to 10-8-10-6 mol/l curcumin resulted in internalization and
      colocalization of BAR-2 and curcumin (FRET) that was prevented by oxidative
      stress (10-3 mol/l CoCl2), supporting that stress prevented internalization of
      the BAR agonist with the micromolar agonist. This study presents novel data
      supporting that distinct pools of BARs are differentially available after
      inflammatory insult. NEW & NOTEWORTHY Preexposure to an oxidative/nitrosative
      proinflammatory insult provides a "protective preconditioning" against future
      oxidative damage. We examined immediate vasoactive and molecular consequences of
      a brief preexposure via beta-adrenergic receptor signaling in small arterioles.
      Blocked receptor internalization with elevated reactive oxygen levels coincides
      with a significant and unexpected vasodilation to beta-adrenergic agonists at
      picomolar doses.

PMID- 29569956
TI  - Humoral transfer and intramyocardial signal transduction of protection by remote
      ischemic perconditioning in pigs, rats, and mice.
AB  - Remote ischemic perconditioning (RPER) during ongoing myocardial ischemia reduces
      infarct size. The signal transduction of RPER's cardioprotection is still largely
      unknown. Anesthetized pigs were therefore subjected to RPER by 4 * 5 min/5 min of
      hindlimb ischemia-reperfusion during 60 min of coronary occlusion before 3 h of
      reperfusion. Pigs without RPER served as placebo (PLA). The phosphorylation of
      Akt and ERK [reperfusion injury salvage kinase (RISK) pathway] and STAT3
      [survivor activating factor enhancement (SAFE) pathway] in the area at risk was
      determined by Western blot analysis. Wortmannin/U0126 or AG490 was used for
      pharmacological RISK or SAFE blockade, respectively. Pig plasma/plasma dialysate
      sampled after RPER or PLA, respectively, was transferred to isolated rat and
      mouse hearts subjected to 30 min/120 min of global ischemia-reperfusion.
      Mitochondria were isolated from rat hearts at early reperfusion. Isolated mouse
      cardiomyocytes were subjected to 1 h of hypoxia/5 min of reoxygenation without
      and with prior plasma dialysate incubation. RPER reduced infarct size in pigs to
      21 +/- 15% versus 44 +/- 9% in PLA (percentage of the area at risk, mean +/- SD,
      P < 0.05) and increased STAT3 phosphorylation at early reperfusion. AG490 but not
      RISK blockade abolished the protection. RPER plasma/plasma dialysate reduced
      infarct size in rat (22 +/- 3% of ventricular mass vs. 40 +/- 11% with PLA
      plasma, P < 0.05) and mouse (29 +/- 4% vs. 63 +/- 8% with PLA plasma dialysate, P
      < 0.05) hearts and improved mitochondrial function (e.g., increased respiration,
      ATP formation, and calcium retention capacity and decreased reactive oxygen
      species formation). RPER dialysate also improved the viability of mouse
      cardiomyocytes after hypoxia/reoxygenation. RISK or SAFE blockade each abrogated
      these beneficial effects. NEW & NOTEWORTHY Remote ischemic perconditioning
      salvages the myocardium in patients with acute infarction. We identified a signal
      transduction with humoral transfer and STAT3 activation in pigs and an
      involvement of reperfusion injury salvage kinases and STAT3 in rat and mouse
      hearts, along with better cardiomyocyte viability and mitochondrial function.

PMID- 29569957
TI  - Protein tyrosine phosphatase 1B inactivation limits aging-associated heart
      failure in mice.
AB  - We have previously shown that protein tyrosine phosphatase 1B (PTP1B)
      inactivation in mice [PTP1B-deficient (PTP1B-/-) mice] improves left ventricular
      (LV) angiogenesis, perfusion, remodeling, and function and limits endothelial
      dysfunction after myocardial infarction. However, whether PTP1B inactivation
      slows aging-associated cardiovascular dysfunction remains unknown. Wild-type (WT)
      and PTP1B-/- mice were allowed to age until 18 mo. Compared with old WT mice, in
      which aging increased the LV mRNA expression of PTP1B, old PTP1B-/- mice had 1)
      reduced cardiac hypertrophy with decreased LV mRNA levels of hypertrophic markers
      and atrial and brain natriuretic peptides, 2) lower LV fibrosis (collagen: 16 +/-
      3% in WT mice and 5 +/- 3% in PTP1B-/- mice, P < 0.001) with decreased mRNA
      levels of transforming growth-factor-beta1 and matrix metalloproteinase-2, and 3)
      higher LV capillary density and lower LV mRNA level of hypoxic inducible factor
      1alpha, which was associated over time with a higher rate of proangiogenic M2
      type macrophages and a stable LV mRNA level of VEGF receptor-2. Echocardiography
      revealed an age-dependent LV increase in end-diastolic volume in WT mice together
      with alterations of fractional shortening and diastole (transmitral Doppler E-to
      A wave ratio). Invasive hemodynamics showed better LV systolic contractility and
      better diastolic compliance in old PTP1B-/- mice (LV end-systolic pressure-volume
      relation: 13.9 +/- 0.9 in WT mice and 18.4 +/- 1.6 in PTP1B-/- mice; LV end
      diastolic pressure-volume relation: 5.1 +/- 0.8 mmHg/relative volume unit in WT
      mice and 1.2 +/- 0.3 mmHg/relative volume unit in PTP1B-/- mice, P < 0.05). In
      addition, old PTP1B-/- mice displayed a reduced amount of LV reactive oxygen
      species. Finally, in isolated resistance mesenteric arteries, PTP1B inactivation
      reduced aging-associated endothelial dysfunction (flow-mediated dilatation: -0.4
      +/- 2.1% in WT mice and 8.2 +/- 2.8% in PTP1B-/- mice, P < 0.05). We conclude
      that PTP1B inactivation slows aging-associated LV remodeling and dysfunction and
      reduces endothelial dysfunction in mesenteric arteries. NEW & NOTEWORTHY The
      present study shows that protein tyrosine phosphatase 1B inactivation in aged
      mice improves left ventricular systolic and diastolic function associated with
      reduced adverse cardiac remodeling (hypertrophy, fibrosis, and capillary
      rarefaction) and limits vascular endothelial dysfunction. This suggests that
      protein tyrosine phosphatase 1B inhibition could be an interesting treatment
      approach in age-related cardiovascular dysfunction.

PMID- 29569958
TI  - Influence of long-term treatment with glyceryl trinitrate on remote ischemic
      conditioning.
AB  - Remote ischemic conditioning (RIC) protects against sustained myocardial
      ischemia. Because of overlapping mechanisms, this protection may be altered by
      glyceryl trinitrate (GTN), which is commonly used in the treatment of patients
      with chronic ischemic heart disease. We investigated whether long-term GTN
      treatment modifies the protection by RIC in the rat myocardium and human
      endothelium. We studied infarct size (IS) in rat hearts subjected to global
      ischemia-reperfusion (I/R) in vitro and endothelial function in healthy
      volunteers subjected to I/R of the upper arm. In addition to allocated treatment,
      rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO)
      scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4)
      GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN
      treatment for 7 consecutive days, applied subcutaneously or 2 h daily
      transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 +/-
      12%, P = 0.007 and 15 +/- 5%, P = 0.002) compared with control (35 +/- 13%). RIC
      and long-term GTN treatment in combination did not reduce IS (29 +/- 12%, P =
      0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and
      long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01
      vs. baseline). Separately, RIC and long-term GTN prevented the reduction in
      endothelial function caused by I/R; given in combination, prevention was lost.
      RIC and long-term GTN treatment both protect against rat myocardial and human
      endothelial I/R injury through ROS and NO-dependent mechanisms. However, when
      given in combination, RIC and long-term GTN treatment fail to confer protection.
      NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl
      trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both
      human endothelium and rat myocardium. However, combined application of RIC and
      long-term GTN treatment abolishes the individual protective effects of RIC and
      GTN treatment on ischemia-reperfusion injury, suggesting an interaction of
      clinical importance.

PMID- 29569955
TI  - Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and
      MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive
      pregnancy.
AB  - Preeclampsia is a complication of pregnancy manifested as maternal hypertension
      (HTN) and fetal intrauterine growth restriction, with unclear mechanisms.
      Placental ischemia increases antiangiogenic soluble fms-like tyrosine kinase-1
      (sFlt-1) relative to angiogenic placental growth factor (PlGF); however, the
      molecular targets are unclear. To test the hypothesis that placental ischemia
      induced changes in sFlt-1 and PlGF target vascular and uteroplacental matrix
      metalloproteinases (MMPs), we tested whether raising the sFlt-1-to-PlGF ratio by
      infusing sFlt-1 (10 ug.kg-1.day-1) in pregnant (Preg) rats increases blood
      pressure (BP) and alters MMPs and whether correcting sFlt-1/PlGF by infusing PlGF
      (20 ug.kg-1.day-1) in Preg rats with reduced uterine perfusion pressure (RUPP)
      improves BP and reverses the changes in MMPs. On gestational day 19, BP was
      higher and the litter size and uterine, placenta, and pup weight were less in
      Preg + sFlt-1 and RUPP than Preg rats and restored in RUPP + PlGF versus RUPP
      rats. Gelatin and casein zymography and Western blots revealed decreases in MMP-2
      and MMP-9 and increases in MMP-1 and MMP-7 in the aorta, uterine artery, uterus,
      and placenta of Preg + sFlt-1 and RUPP versus Preg rats, which were reversed in
      RUPP + PlGF versus RUPP rats. Collagen types I and IV were more abundant in Preg
      + sFlt-1 and RUPP versus Preg rats and were reversed in RUPP + PlGF versus RUPP
      rats. Thus, PlGF reverses decreased vascular and uteroplacental MMP-2 and MMP-9
      and increased MMP-1, MMP-7, and collagen types I and IV induced by placental
      ischemia and sFlt-1 in HTN in pregnancy. Angiogenic factors and MMP modulators
      could rectify changes in MMPs and collagen, restore vascular and uteroplacental
      remodeling, and improve HTN and intrauterine growth restriction in preeclampsia.
      NEW & NOTEWORTHY Understanding the mechanisms of preeclampsia could help in its
      prevention and management. This study shows that correcting soluble fms-like
      tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) imbalance by infusing
      PlGF reverses the decreases in vascular and uteroplacental matrix
      metalloproteinase (MMP)-2 and MMP-9 and the increases in MMP-1, MMP-7, and
      collagen types I and IV induced by placental ischemia and antiangiogenic sFlt-1
      in hypertension in pregnancy. Angiogenic factors and MMP modulators could rectify
      changes in vascular and uteroplacental MMPs and collagen content and ameliorate
      hypertension and intrauterine growth restriction in preeclampsia.

PMID- 29569959
TI  - Noninvasive assessment of the common carotid artery hemodynamics with increasing
      exercise work rate using wave intensity analysis.
AB  - Noninvasively determined local wave speed ( c) and wave intensity (WI) parameters
      provide insights into arterial stiffness and cardiac-vascular interactions in
      response to physiological perturbations. However, the effects of incremental
      exercise and subsequent recovery on c and WI have not been fully established. We
      examined the changes in c and WI parameters in the common carotid artery (CCA)
      during exercise and recovery in eight young, healthy male athletes. Ultrasound
      measurements of CCA diameter and blood flow velocity were acquired at rest,
      during five stages of incremental exercise (up to 70% maximum work rate), and
      throughout 1 h of recovery, and noninvasive WI analysis [diameter-velocity ( DU)
      approach] was performed. During exercise, c increased (+136%), showing increased
      stiffness with work rate. All peak and area of forward compression, backward
      compression, and forward expansion waves increased during exercise (+452%, +700%,
      and +900%, respectively). However, WI reflection indexes and CCA resistance did
      not significantly change from rest to exercise. Furthermore, wave speed and the
      magnitude of all waves returned to baseline within 5 min of recovery, suggesting
      that the effects of exercise in the investigated parameters of young, healthy
      individuals were transient. In conclusion, incremental exercise was associated
      with an increase in local CCA stiffness and increases in all wave parameters,
      indicative of enhanced ventricular contractility and improved late-systolic blood
      flow deceleration. NEW & NOTEWORTHY We examined hemodynamics of the common
      carotid artery using noninvasive application of wave intensity analysis during
      exercise and recovery. The hemodynamic adjustments to exercise were associated
      with increases in local common carotid artery stiffness and all waves'
      parameters, with the latter indicating enhanced ventricular contractility and
      improved late systolic blood flow deceleration.

PMID- 29569960
TI  - Is there a superior simulator for human anatomy education? How virtual dissection
      can overcome the anatomic and pedagogic limitations of cadaveric dissection.
AB  - Educators must select the best tools to teach anatomy to future physicians and
      traditionally, cadavers have always been considered the "gold standard" simulator
      for living anatomy. However, new advances in technology and radiology have
      created new teaching tools, such as virtual dissection, which provide students
      with new learning opportunities. Virtual dissection is a novel way of studying
      human anatomy through patient computed tomography (CT) scans. Through touchscreen
      technology, students can work together in groups to "virtually dissect" the CT
      scans to better understand complex anatomic relationships. This article presents
      the anatomic and pedagogic limitations of cadaveric dissection and explains what
      virtual dissection is and how this new technology may be used to overcome these
      limitations.

PMID- 29569961
TI  - Through measurement positive care in psychiatry is conquered.

PMID- 29569962
TI  - A novel uromodulin mutation in autosomal dominant tubulointerstitial kidney
      disease: a pedigree-based study and literature review.
AB  - Autosomal dominant tubulointerstitial kidney disease caused by mutations in
      uromodulin gene (ADTKD-UMOD) is a spectrum of hereditary renal disorders,
      characterized by early-onset hyperuricemia, gout and progressive nephropathy.
      This study presented a novel UMOD mutation in an ADTKD pedigree and reviewed
      studies in Chinese population. The index patient is a 16-year-old girl with
      hypertension, hyperuricemia and normal serum creatinine level. Four affected and
      six unaffected members were available for genetic screen. The mutation analysis
      was performed by next-generation sequencing and direct sequencing. A literature
      research was conducted to review Chinese ADTKD-UMOD cases. MEDLINE and Chinese
      Biomedicine Databases were searched with 'uromodulin', 'juvenile gout' and their
      related terms. Genetic sequencing revealed a de novo mutation within exon 3
      (Cys223Gly), which was co-segregating with phenotype in this pedigree. In the
      review, four studies and our study involving a total of 67 ADTKD patients from 11
      families were identified. Of these patients, 27 were confirmed to carry UMOD
      mutations. Mutations occurred in exon 3 were commonly observed, while mutations
      within exon 4, 5 and 9 occurred less frequently in Chinese ADTKD-UMOD cases.
      Among these cases, median age of symptom onset was 26.5 years, median age of end
      stage renal diseases (ESRD) or death by ESRD was 41.9 years without renal
      replacement treatment. Phenotype caused by mutations in D8C domain seemed to be
      severe than those in GPI domain. Compared with patients of other race, Chinese
      ADTKD-UMOD patients advanced more aggressively to ESRD.

PMID- 29569963
TI  - Analysis of alterations in white matter integrity of adult patients with comitant
      exotropia.
AB  - Objective This study was performed to investigate structural abnormalities of the
      white matter in patients with comitant exotropia using the tract-based spatial
      statistics (TBSS) method. Methods Diffusion tensor imaging data from magnetic
      resonance images of the brain were collected from 20 patients with comitant
      exotropia and 20 age- and sex-matched healthy controls. The FMRIB Software
      Library was used to compute the diffusion measures, including fractional
      anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial
      diffusivity (RD). These measures were obtained using voxel-wise statistics with
      threshold-free cluster enhancement. Results The FA values in the right inferior
      fronto-occipital fasciculus (IFO) and right inferior longitudinal fasciculus were
      significantly higher and the RD values in the bilateral IFO, forceps minor, left
      anterior corona radiata, and left anterior thalamic radiation were significantly
      lower in the comitant exotropia group than in the healthy controls. No
      significant differences in the MD or AD values were found between the two groups.
      Conclusions Alterations in FA and RD values may indicate the underlying
      neuropathologic mechanism of comitant exotropia. The TBSS method can be a useful
      tool to investigate neuronal tract participation in patients with this disease.

PMID- 29569965
TI  - Analysis of risk factors for cervical lymph node metastases in patients with
      sporadic medullary thyroid carcinoma.
AB  - Objective Medullary thyroid carcinoma (MTC) is classified as either sporadic or
      inherited. This study was performed to analyze the risk factors for cervical
      lymph node metastases and predict the indication for prophylactic lateral neck
      dissection in patients with sporadic MTC. Methods Sixty-five patients with
      sporadic MTC were retrospectively reviewed. Univariate analysis with the chi
      square test and multiple logistic regression analysis were applied to identify
      the clinicopathological features (sex, age, tumor size, number of tumor foci,
      capsule or vascular invasion, and others) associated with cervical lymph node
      metastases. Results The metastasis rates in the central and lateral compartments
      were 46.2% (30/65) and 40.0% (26/65), respectively. The incidence of cervical
      lymph node metastases was significantly higher in patients with a tumor size of
      >1 cm, tumor multifocality, and thyroid capsule invasion. Only thyroid capsule
      invasion was an independent predictive factor for central compartment metastases
      and lateral neck metastases. The possibility of central compartment metastases
      was significantly higher when the preoperative serum carcinoembryonic antigen
      concentration was >30 ng/mL (60.0% vs. 34.3%). Conclusions MTC is associated with
      a high incidence of cervical lymph node metastases. Prophylactic lateral node
      dissection is necessary in patients with thyroid capsule invasion or a high serum
      carcinoembryonic antigen concentration.

PMID- 29569966
TI  - Use of YouTube to reduce mental health stigma.

PMID- 29569964
TI  - Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like
      behaviours in mice by modulating neuroinflammation and monoamine
      neurotransmitters in the hippocampus.
AB  - CONTEXT: Depression is an inflammatory, commonly occurring and lethal psychiatric
      disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae),
      commonly called Timur, has high medicinal value and is used ethnomedicinally for
      the treatment of various diseases. OBJECTIVE: To evaluate the effect of hexane
      extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression
      like behaviour in Swiss albino mice. MATERIALS AND METHODS: Mice were treated
      with ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) for
      14 days. On 14th day of the treatment, depression-like behaviour was induced by
      LPS (0.83 mg/kg injected i.p.) and after 24 h of LPS administration, it was
      assessed by measuring behavioural parameters and biochemical estimations.
      RESULTS: Behavioural tests, including the open field test, forced swimming test,
      tail suspension test and sucrose preference test revealed that ZAHE (100 and 200
      mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) alleviated the depression
      symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced
      alterations in the concentrations of norepinephrine and serotonin (5-HT) and
      inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory
      cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated
      to be LD50 > 2500 mg/kg. DISCUSSION AND CONCLUSIONS: This study showed that LPS
      induced depression in mice was significantly prevented by ZAHE at both the
      dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering
      monoaminergic neurotransmitters in the brain combined with its anti-inflammatory
      potential. Thus, it could be an effective therapeutic against inflammation
      induced depression and other brain disorders.

PMID- 29569967
TI  - Characteristics of adults who stutter by treatments sought.
AB  - Several treatment approaches are available for adults who stutter, including
      speech treatment, cognitive behaviour therapy (CBT) treatment for anxiety, and a
      combination of both. It is useful to determine whether any differences exist
      between adults who stutter enrolled in different types of treatment. Therefore,
      the purpose of this study was to compare demographic, speech, and psychological
      characteristics of adults who stutter enrolled in speech, psychological, and
      combined treatment programs. Participants were 288 adults who stuttered (18-80
      years) enrolled in one of three different treatment programs: Speech Treatment
      for stuttering (n = 134), Anxiety Treatment for anxiety about stuttering (n =
      70), or Speech Treatment for Stuttering With or Without Anxiety Treatment (n =
      84). Participants completed a range of demographic, speech, and psychological
      measures prior to the start of treatment. A significantly higher proportion of
      participants in the Anxiety Treatment group were in a personal relationship than
      the other treatment groups. The Anxiety Treatment group had higher average age
      than the other treatment groups. The Speech Treatment group also demonstrated
      significantly higher self-rated stuttering severity than the Anxiety Treatment
      group, even though there were no significant difference between groups for
      clinician-rated percentage of syllables stuttered. Although most characteristics
      of adults who stuttered did not vary by treatment type, the present findings
      suggest that adults who stutter enrolled in speech treatment perceived their
      stuttering as more severe, which may have prompted treatment seeking. Further
      research is needed regarding the supportive influence of personal relationship
      for those with the disorder.

PMID- 29569969
TI  - Implementation of team-based learning on a large scale: Three factors to keep in
      mind.
AB  - Team-based learning (TBL) is a structured form of small group learning that can
      be scaled up for delivery in large classes. The principles of successful TBL
      implementation are well established. TBL has become widely practiced in medical
      schools, but its use is typically limited to certain courses or parts of courses.
      Implementing TBL on a large scale, across different courses and disciplines, is
      the next logical step. The Lee Kong Chian School of Medicine (LKCMedicine), a
      partnership between Nanyang Technological University, Singapore and Imperial
      College London, admitted its first students in 2013. This new undergraduate
      medical program, developed collaboratively by faculty at both institutions, uses
      TBL as its main learning and teaching strategy, replacing all face-to-face
      lectures. TBL accounts for over 60% of the curriculum in the first two years, and
      there is continued learning through TBL during campus teaching in the remaining
      years. This paper describes our experience of rolling out TBL across all years of
      the medical curriculum, focusing on three success factors: (1) "team-centric"
      learning spaces, to foster active, collaborative learning; (2) an e-learning
      ecosystem, seamlessly integrated to support all phases of the TBL process and (3)
      teaching teams in which experts in pedagogical process (TBL Facilitators) co
      teach with experts in subject matter (Content Experts).

PMID- 29569968
TI  - Organizational Health Literacy: Review of Theories, Frameworks, Guides, and
      Implementation Issues.
AB  - Organizational health literacy is described as an organization-wide effort to
      transform organization and delivery of care and services to make it easier for
      people to navigate, understand, and use information and services to take care of
      their health. Several health literacy guides have been developed to assist
      healthcare organizations with this effort, but their content has not been
      systematically reviewed to understand the scope and practical implications of
      this transformation. The objective of this study was to review (1) theories and
      frameworks that inform the concept of organizational health literacy, (2) the
      attributes of organizational health literacy as described in the guides, (3) the
      evidence for the effectiveness of the guides, and (4) the barriers and
      facilitators to implementing organizational health literacy. Drawing on a
      metanarrative review method, 48 publications were reviewed, of which 15 dealt
      with the theories and operational frameworks, 20 presented health literacy
      guides, and 13 addressed guided implementation of organizational health literacy.
      Seven theories and 9 operational frameworks have been identified. Six health
      literacy dimensions and 9 quality-improvement characteristics were reviewed for
      each health literacy guide. Evidence about the effectiveness of health literacy
      guides is limited at this time, but experiences with the guides were positive.
      Thirteen key barriers (conceived also as facilitators) were identified. Further
      development of organizational health literacy requires a strong and a clear
      connection between its vision and operationalization as an implementation
      strategy to patient-centered care. For many organizations, becoming health
      literate will require multiple, simultaneous, and radical changes. Organizational
      health literacy has to make sense from clinical and financial perspectives in
      order for organizations to embark on such transformative journey.

PMID- 29569970
TI  - Spinal dura mater: biophysical characteristics relevant to medical device
      development.
AB  - Understanding the relevant biophysical properties of the spinal dura mater is
      essential to the design of medical devices that will directly interact with this
      membrane or influence the contents of the intradural space. We searched the
      literature and reviewed the pertinent characteristics for the design,
      construction, testing, and imaging of novel devices intended to perforate,
      integrate, adhere or reside within or outside of the spinal dura mater. The
      spinal dura mater is a thin tubular membrane composed of collagen and elastin
      fibres that varies in circumference along its length. Its mechanical properties
      have been well-described, with the longitudinal tensile strength exceeding the
      transverse strength. Data on the bioelectric, biomagnetic, optical and thermal
      characteristics of the spinal dura are limited and sometimes taken to be similar
      to those of water. While various modalities are available to visualise the spinal
      dura, magnetic resonance remains the best modality to segment its structure. The
      reaction of the spinal dura to imposition of a foreign body or other
      manipulations of it may compromise its biomechanical and immune-protective
      benefits. Therefore, dural sealants and replacements are of particular clinical,
      research and commercial interest. In conclusion, existing devices that are in
      clinical use for spinal cord stimulation, intrathecal access or intradural
      implantation largely adhere to traditional designs and their attendant
      limitations. However, if future devices are built with an understanding of the
      dura's properties incorporated more fully into the designs, there is potential
      for improved performance.

PMID- 29569971
TI  - Src family kinase inhibitor bosutinib enhances retinoic acid-induced
      differentiation of HL-60 leukemia cells.
AB  - The acute promyelocytic leukemia (APL) has been treated with all-trans retinoic
      acid (RA) for decades. While RA has largely been ineffective in non-APL AML
      subtypes, co-treatments combining RA and other agents are currently in clinical
      trials. Using the RA-responsive non-APL AML cell line HL-60, we tested the
      efficacy of the Src family kinase (SFK) inhibitor bosutinib on RA-induced
      differentiation. HL-60 has been recently shown to bear fidelity to a subtype of
      AML that respond to RA. We found that co-treatment with RA and bosutinib enhanced
      differentiation evidenced by increased CD11b expression, G1/G0 cell cycle arrest,
      and respiratory burst. Expression of the SFK members Fgr and Lyn was enhanced,
      while SFK activation was inhibited. Phosphorylation of several sites of c-Raf was
      increased and expression of AhR and p85 PI3K was enhanced. Expression of c-Cbl
      and mTOR was decreased. Our study suggests that SFK inhibition enhances RA
      induced differentiation and may have therapeutic value in non-APL AML.

PMID- 29569972
TI  - Expression of TRIM28 correlates with proliferation and Bortezomib-induced
      apoptosis in B-cell non-Hodgkin lymphoma.
AB  - Tripartite motif containing 28 (TRIM28) as a transcriptional co-repressor has
      been reported playing a role in regulating DNA damage response (DDR), cell
      differentiation, immune response, and tumorigenesis. The present study was
      performed to explore the biological function and clinical significance of TRIM28
      in B-cell non-Hodgkin lymphoma (B-NHL). Results of the study displayed that high
      expression of TRIM28 was positively associated with the poorer survival of B-NHL
      patients as an independent prognostic factor. In addition, TRIM28 could promote
      the B-NHL cells proliferation through modulating cell cycle progression. The
      change of cyclinA, P21, and PCNA expression after TRIM28 expression modified
      further illustrated the mechanism in which TRIM28 participated in cell
      proliferation progression. Moreover, inhibition TRIM28 expression in B-NHL cells
      enhanced the sensibility to Bortezomib by regulating p53-mediated apoptosis
      pathway. Taken together, the present study showed that TRIM28 functions as a
      tumor promoter in B-NHL and may be a novel target for drug resistance to
      Bortezomib.

PMID- 29569973
TI  - Black Raspberry Extract Enhances LDL Uptake in HepG2 Cells by Suppressing PCSK9
      Expression to Upregulate LDLR Expression.
AB  - Black raspberry extract (BRE) has been widely used for treating prostate and
      urinary diseases and hyperlipidemia in Asia due to its significant lipid-lowering
      effects. The aim of this investigation was to evaluate the
      antihypercholesterolemia activity of BRE and the potential molecular mechanisms
      responsible for its antihypercholesterolemia activity by regulation of proprotein
      convertase subtilisin/kexin type 9 (PCSK9) expression in the human liver cell
      line HepG2. Reporter-based functional assay was used to identify herbal extracts
      that suppress PCSK9 expression in the HepG2 cells. Quantitative real-time
      polymerase chain reaction, Western blot analysis, and immunofluorescence staining
      were used to evaluate whether BRE modulates low-density lipoprotein receptor
      (LDLR) expression by repressing the hepatic expression of PCSK9. The LDLR
      activity of the HepG2 cells was determined using an LDL uptake assay. Our finding
      revealed that BRE modulates LDLR expression by suppressing the hepatic expression
      of PCSK9. We found that the combination of simvastatin and BRE caused the
      synergic induction of LDLR expression and LDL-C uptake, whereas simvastatin alone
      increased the expression of PCSK9 in the HepG2 cells. These results clearly
      demonstrated that the BRE from black raspberry suppressed simvastatin-induced
      PCSK9 expression and improved LDL-C uptake by hepatocytes through the induction
      of LDLR expression. These results suggest that the suppression of PCSK9
      expression by BRE may potentiate the hypolipidemic effect of statins.

PMID- 29569974
TI  - Efficacy of ibrutinib as first-line treatment of tumoral Bing-Neel syndrome.

PMID- 29569975
TI  - Navigating the changing multiple myeloma treatment landscape: clinical practice
      patterns of MM patients treated in- and outside German DSMM study group trials.

PMID- 29569977
TI  - Simulation of key interventions for seasonal influenza outbreak control at school
      in Changsha, China.
AB  - Objective To use a mathematical model to simulate an influenza outbreak in a
      school in order to assess the effectiveness of isolation (Iso), antiviral
      therapeutics, antiviral prophylactics (P), vaccination prior to the outbreak, and
      school closure (for 1 [S1w], 2 or 3 weeks). Methods This study developed a
      susceptible-exposed-infectious/asymptomatic-recovered model to estimate the
      effectiveness of commonly used interventions for seasonal influenza outbreaks in
      school. Results The most effective single-intervention strategy was isolation
      with a total attack rate of 1.99% and an outbreak duration of 30 days. The
      additional effectiveness of antiviral therapeutics and prophylactics and
      vaccination (prior to the outbreak) strategies were not obvious. Although Iso+P,
      P+Iso+S1w, four-, and five-combined intervention strategies had commendable
      effectiveness, total attack rate decreased only slightly, and outbreak duration
      was shortened by 9 days maximum, compared with the single-intervention isolation
      strategy. School closure for 1, 2 or 3 weeks was futile or even
      counterproductive. Conclusion Isolation, as a single intervention, was the most
      effective in terms of reducing the total attack rate and the duration of the
      outbreak.

PMID- 29569976
TI  - Polyphenol-Rich Blackcurrant Juice Prevents Endothelial Dysfunction in the
      Mesenteric Artery of Cirrhotic Rats with Portal Hypertension: Role of Oxidative
      Stress and the Angiotensin System.
AB  - Chronic liver diseases with portal hypertension are characterized by a
      progressive vasodilatation, endothelial dysfunction, and NADPH oxidase-derived
      vascular oxidative stress, which have been suggested to involve the angiotensin
      system. This study evaluated the possibility that oral intake of polyphenol-rich
      blackcurrant juice (PRBJ), a rich natural source of antioxidants, prevents
      endothelial dysfunction in a rat model of cirrhosis induced by chronic bile duct
      ligation (CBDL), and, if so, determined the underlying mechanism. Male Wistar
      rats received either control drinking water or water containing 60 mg/kg gallic
      acid equivalents of PRBJ for 3 weeks before undergoing surgery with CBDL or sham
      surgery. After 4 weeks, vascular reactivity was assessed in mesenteric artery
      rings using organ chambers. Both the acetylcholine-induced nitric oxide (NO)- and
      endothelium-dependent hyperpolarization (EDH)-mediated relaxations in mesenteric
      artery rings were significantly reduced in CBDL rats compared to sham rats. An
      increased level of oxidative stress and expression of NADPH oxidase subunits, COX
      2, NOS, and of the vascular angiotensin system are observed in arterial sections
      in the CBDL group. Chronic intake of PRBJ prevented the CBDL-induced impaired EDH
      mediated relaxation, oxidative stress, and expression of the different target
      proteins in the arterial wall. In addition, PRBJ prevented the CBDL-induced
      increase in the plasma level of proinflammatory cytokines (interleukin [IL]
      1alpha, monocyte chemotactic protein 1, and tumor necrosis factor alpha) and the
      decrease of the anti-inflammatory cytokine, IL-4. Altogether, these observations
      indicate that regular ingestion of PRBJ prevents the CBDL-induced endothelial
      dysfunction in the mesenteric artery most likely by normalizing the level of
      vascular oxidative stress and the angiotensin system.

PMID- 29569978
TI  - Anticipatory guidance in type 2 diabetes to improve disease management; next
      steps after basal insulin.
AB  - The alarming rise in the number of people living with type 2 diabetes (T2D)
      presents primary care physicians with increasing challenges associated with long
      term chronic disease care. Studies have shown that the majority of patients are
      not achieving or maintaining glycemic goals, putting them at risk of a wide range
      of diabetes-related complications. Disease- and self-management programs have
      been shown to help patients improve their glycemic control, and are likely to be
      of particular benefit for patients with diabetes dealing with these issues.
      Anticipatory guidance is an individualized, proactive approach to patient
      education and counseling by a health-care professional to support patients in
      better coping with problems before they arise. It has been shown to improve
      disease outcomes in a variety of chronic conditions, including diabetes. While
      important at all stages, anticipatory guidance may be of particular importance
      during changes in treatment regimens, and especially during transition to, and
      escalation of, insulin-based regimens. The aim of this article is to provide
      advice to physicians on anticipatory guidance for basal-insulin dosing, focusing
      on appropriate basal-insulin-dose increase and prevention of potentially
      deleterious basal-insulin doses, so called overbasalization. It also provides an
      overview of new treatment options for patients with T2D who are not well
      controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin
      and glucagon-like peptide-1 receptor agonists, and advice on the type of
      anticipatory guidance needed to ensure safe and appropriate switching to these
      therapies.

PMID- 29569979
TI  - An abscopal effect may augment PD-1 inhibition in refractory classical Hodgkin
      lymphoma.

PMID- 29569981
TI  - Regulatory T-cells within bone marrow-derived stem cells actively confer
      immunomodulatory and neuroprotective effects against stroke.
AB  - Regulatory T-cells (Tregs) may exert a neuroprotective effect on ischemic stroke
      by inhibiting both inflammation and effector T-cell activation. Transplantation
      of human bone marrow-derived stem cells (BMSCs) in ischemic stroke affords
      neuroprotection that results in part from the cells' anti-inflammatory property.
      However, the relationship between Tregs and BMSCs in treatment of ischemic stroke
      has not been fully elucidated. Here, we tested the hypothesis that Tregs within
      the BMSCs represent active mediators of immunomodulation and neuroprotection in
      experimental stroke. Primary rat neuronal cells were subjected to an oxygen
      glucose deprivation and reperfusion (OGD/R) condition. The cells were re-perfused
      and co-cultured with Tregs and/or BMSCs. We detected a minority population of
      Tregs within BMSCs with both immunocytochemistry (ICC) and flow cytometry
      identifying cells expressing phenotypic markers of CD4, CD25, and FoxP3 protein.
      BMSCs with the native population of Tregs conferred maximal neuroprotection
      compared to the treatment conditions containing 0%, 10%, and 100% relative ratio
      Tregs. Increasing the Treg population resulted in increased IL6 secretion and
      decreased FGF-beta secretion by BMSCs. This study shows that a minority
      population of Tregs exists within the therapeutic BMSC population, which serves
      as robust mediators of the immunomodulatory and neuroprotective effect provided
      by BMSC transplantation.

PMID- 29569980
TI  - Synergistic action of inflammation and lipid dysmetabolism on kidney damage in
      rats.
AB  - In kidney disease, inflammation and lipid dysmetabolism are often associated
      together, however, the effect and mechanism of inflammatory mediators and lipid
      dysmetabolism on kidney damage is still unclear. In this study, Wistar rats were
      randomized into four groups: normal diet + saline (Group N), high-fat diet (HF)+
      saline (Group HF), normal diet + adriamycin (Group ADR), HF + adriamycin (Group
      ADR + HF). After 10 weeks of feeding, rats in each group were randomly
      sacrificed. We found that the protein content of urine in ADR and ADR + HF groups
      were significantly higher than that of group N and HF while the serum levels of
      total protein and albumin in the ADR and ADR + HF groups decreased
      correspondingly. The serum levels of triglyceride, total cholesterol and low
      density lipoprotein in the HF, ADR and ADR + HF groups increased. In the
      treatment groups, mesangial proliferation, matrix accumulation, tubular
      vacuolization, inflammatory cell infiltration and fat deposition were detected.
      These pathological changes were the most serious in the ADR + HF group. The
      expression of tumor necrosis factor-alpha (TNF-alpha) and transforming growth
      factor-beta1 (TGF-beta1) were increased in each treatment group, especially in
      the ADR + HF group. Our results suggested that the inflammatory factors and
      abnormal lipid levels can activate the inflammatory response in kidney of the
      Wistar rats, and lead to a series of pathological changes in renal tissue, and
      inflammatory factors and lipid dysmetabolism can aggravate damage in the kidney.

PMID- 29569982
TI  - Quercetin Reduces Tumor Necrosis Factor Alpha-Induced Muscle Atrophy by
      Upregulation of Heme Oxygenase-1.
AB  - The inflammatory cytokine tumor necrosis factor alpha (TNFalpha), upregulated in
      the obese condition, promotes protein degradation and is implicated in obesity
      related skeletal muscle atrophy and age-related sarcopenia. Quercetin, a
      flavonoid, elicits antioxidative and anti-inflammatory activities. In this study,
      we investigated the effect of quercetin on TNFalpha-induced skeletal muscle
      atrophy as well as its potential mechanism of action. In this study, we observed
      that quercetin suppressed expression of TNFalpha-induced atrophic factors such as
      MAFbx/atrogin-1 and MuRF1 in myotubes, and it enhanced heme oxygenase-1 (HO-1)
      protein level accompanied by increased nuclear translocation of nuclear factor
      erythroid 2-related factor 2 (Nrf2) in myotubes. The HO-1 inhibitor ZnPP
      suppressed the inhibitory actions of quercetin on TNFalpha-induced atrophic
      responses and degradation of IkappaB-alpha in myotubes. Moreover, quercetin
      supplementation to high-fat diet-fed obese mice inhibited obesity-induced
      atrophic responses in skeletal muscle, accompanied by upregulation of HO-1 and
      inactivation of nuclear factor-kappa B (NF-kappaB), and the quercetin actions
      were attenuated in Nrf2-deficient mice. These findings suggest that quercetin
      protects against TNFalpha-induced muscle atrophy under obese conditions through
      Nrf2-mediated HO-1 induction accompanied by inactivation of NF-kappaB. Quercetin
      may be used as a dietary supplement to protect against obesity-induced skeletal
      muscle atrophy.

PMID- 29569983
TI  - The development of a novel high-precision major depressive disorder screening
      system using transient autonomic responses induced by dual mental tasks.
AB  - 12.6% of major depressive disorder (MDD) patients have suicide intent, while it
      has been reported that 43% of patients did not consult their doctors for MDD,
      automated MDD screening is eagerly anticipated. Recently, in order to achieve
      automated screening of MDD, biomarkers such as multiplex DNA methylation profiles
      or physiological method using near infra-red spectroscopy (NIRS) have been
      studied, however, they require inspection using 96-well DNA ELIZA kit after blood
      sampling or significant cost. Using a single-lead electrocardiography (ECG), we
      developed a high-precision MDD screening system using transient autonomic
      responses induced by dual mental tasks. We developed a novel high precision MDD
      screening system which is composed of a single-lead ECG monitor, analogue to
      digital (AD) converter and a personal computer with measurement and analysis
      program written by LabView programming language. The system discriminates MDD
      patients from normal subjects using heat rate variability (HRV)-derived transient
      autonomic responses induced by dual mental tasks, i.e. verbal fluency task and
      random number generation task, via linear discriminant analysis (LDA) adopting
      HRV-related predictor variables (hear rate (HR), high frequency (HF), low
      frequency (LF)/HF). The proposed system was tested for 12 MDD patients (32 +/- 15
      years) under antidepressant treatment from Shizuoka Saiseikai General Hospital
      outpatient unit and 30 normal volunteers (37 +/- 17 years) from Tokyo
      Metropolitan University. The proposed system achieved 100% sensitivity and 100%
      specificity in classifying 42 examinees into 12 MDD patients and 30 normal
      subjects. The proposed system appears promising for future HRV-based high
      precision and low-cost screening of MDDs using only single-lead ECG.

PMID- 29569984
TI  - Prognostic value of serum and tissue HE4 expression in ovarian cancer: a
      systematic review with meta-analysis of 90 studies.
AB  - INTRODUCTION: Ovarian cancer (OC) is one of the leading causes of cancer-related
      death in women. Accumulating evidence showed an evolving role of HE4 in
      monitoring the progression and prognosis of OC but without a comprehensive
      analysis for prognosis and survival data. Areas covered: The present meta
      analysis aims to explore the association of HE4 with survival and the
      clinicopathological features of OC patients. PubMed, Embase, Web of Science and
      the China National Knowledge Infrastructure (CNKI) were searched for relevant
      studies regarding the role of both serum and tissue HE4 expression in ovarian
      cancer. Expert commentary: HE4 has been proposed as the most promising biomarker
      that may complement the CA125 expression and has been approved by the FDA in
      monitoring the follow-up and relapse of OC patients. Our results are in
      accordance with the most recent evidence suggesting its important role in the
      prognostic surveillance of OC and a better performance in the early prediction of
      OC recurrence than CA125.

PMID- 29569985
TI  - Predictive risk factors of failed laryngeal mask airway insertion at first
      attempt.
AB  - Objectives A failed first attempt at laryngeal mask airway (LMA) insertion could
      increase the risk of laryngospasm, hypoxemia, and postoperative sore throat. This
      study was performed to investigate the risk factors for failed first-attempt LMA
      placement. Methods In total, 461 patients who underwent general anesthesia with a
      Supreme LMA (Teleflex Medical, Shanghai, China) and who had an American Society
      of Anesthesiologists (ASA) physical status of I to III were prospectively
      enrolled. The LMA was inserted after anesthetic induction. We recorded the
      insertion conditions and each patient's age, ASA status, body weight, body mass
      index (BMI), duration of anesthesia, size of LMA, and cuff pressure; the years of
      work experience of the anesthesiologists; and the use or nonuse of lidocaine gel
      as a lubricant. Results Successful first-attempt placement of the Supreme LMA was
      achieved in 438 (95.10%) patients, while first-attempt placement failed in 23
      (4.99%). Significant risk factors for failure of first-attempt LMA insertion
      included high age, high body weight, BMI of <20 kg/m2, and insertion without
      using lidocaine gel. Conclusions A patient age of >61 years, high body weight,
      BMI of <20 kg/m2, and insertion without lidocaine gel could significantly
      increase the risk of failed first-attempt Supreme LMA insertion.

PMID- 29569986
TI  - Quantitative positron emission tomography reveals regional differences in aerobic
      glycolysis within the human brain.
AB  - Glucose and oxygen metabolism are tightly coupled in the human brain, with the
      preponderance of the brain's glucose supply used to generate ATP via oxidative
      phosphorylation. A fraction of glucose is consumed outside of oxidative
      phosphorylation despite the presence of sufficient oxygen to do so. We refer to
      this process as aerobic glycolysis. A recent positron emission tomography study
      reported that aerobic glycolysis is uniform within gray matter. Here, we analyze
      the same data and demonstrate robust regional differences in aerobic glycolysis
      within gray matter, a finding consistent with previously published data.

PMID- 29569988
TI  - A Healthy Beverage Consumption Pattern Is Inversely Associated with the Risk of
      Obesity and Metabolic Abnormalities in Korean Adults.
AB  - As the use of beverages in diets is increasing, several studies have examined the
      effect of beverage consumption in human health. Thus, we aimed at identifying
      specific beverage patterns and determining their associations with obesity and
      metabolic syndrome (MetS) risk factors in Korean adults. Based on the Korea
      National Health and Nutrition Examination Survey (KNHANES) 2008-2012 data, 19,800
      Korean adults (>=20 years) with a single 24-h dietary recall and health
      examination data were investigated. All beverage items consumed by participants
      were categorized into 15 beverage groups based on the KNHANES coding system.
      Three major beverage consumption patterns were identified according to factor
      analysis: (1) the "healthy beverage" (high intake of dairy products, 100%
      fruit/vegetable juices and low intake of alcoholic beverages); (2) the "sugar
      sweetened beverage" (high intake of soda, sweetened coffee/tea, and fruit drink);
      and (3) the "unsweetened beverage" (high intake of unsweetened coffee) patterns.
      Multivariable logistic regression analyses were conducted to determine the odds
      of obesity (body mass index >=25 kg/m2) and MetS (defined by National Cholesterol
      Education Program III [NCEP III]) for each beverage pattern after controlling for
      covariates. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for
      associations of the "healthy beverage" pattern with risks of obesity, abdominal
      obesity, and elevated triglycerides, fasting blood glucose (FBG), and blood
      pressure (BP) were 0.88 (0.79-0.98), 0.83 (0.74-0.92), 0.88 (0.78-0.99), 0.85
      (0.79-0.98), and 0.81 (0.72-0.92), respectively. AORs (95% CIs) of associations
      of the "sugar-sweetened beverage" pattern with risks of abdominal obesity,
      elevated FBG and BP were 1.15 (1.03-1.30), 1.14 (1.01-1.29), and 1.18 (1.04
      1.33), respectively. However, no associations were found between the "unsweetened
      beverage" pattern and any parameters examined. Intake of healthy beverages should
      be encouraged to reduce risks of obesity and metabolic abnormalities; however,
      individuals who consume sugar-sweetened beverages should be advised on the
      adverse effects of those beverages on the risk of obesity and MetS.

PMID- 29569987
TI  - Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823
      tumours in nude mice.
AB  - Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9
      yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric
      adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude
      mice. Animals were randomly divided into control and CP groups, which were
      administered NaHCO3 vehicle alone or CP dissolved in NaHCO3 (200 ug/kg body
      weight) daily, respectively. Tumour volume was measured weekly for 6 weeks.
      Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti
      proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined
      using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling
      (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by
      Western blotting. Results There was a significant reduction in tumour volume and
      a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group
      compared with the control group. The percentage of TUNEL-positive or caspase 3
      positive cells significantly increased following CP treatment compared with the
      control group. Tumours from the CP group had higher levels of phosphorylated
      extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT)
      compared with control tumours. Conclusion CP treatment inhibited tumour growth
      and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric
      adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate
      this antitumour activity.

PMID- 29569989
TI  - Eyes to see and ears to hear: sensitivity in research on attachment and culture.
AB  - How and why should attachment researchers engage in research on attachment and
      culture? How should they strive to develop a theoretical perspective that is both
      contextually sensitive and also reflecting species-typical processes of
      evolutionary adaptation? These comments on the remarkable empirical papers of
      this special issue consider what is learned from these studies, what more is
      needed, and directions for future research.

PMID- 29569991
TI  - Examining Perceived Stress, Childhood Trauma and Interpersonal Trauma in
      Individuals With Drug Addiction.
AB  - The investigation of psychosocial factors in relation to opiate addiction is
      limited and typically uses binary measures to assess how incidences of childhood
      trauma correlate with addiction. There has also been a lack of enquiry into how
      experiences of noninterpersonal versus interpersonal trauma may impact drug use
      addiction. In this regard, the current study utilized a novel measurement of
      interpersonal versus noninterpersonal lifetime trauma and a scale assessing
      severity of childhood trauma to examine how these factors may impact patients
      with opioid addiction. The interaction between these factors and current
      perceived stress was also examined. Thirty-six opioid-dependent individuals
      (recruited from the Drug Health Services and Opioid Treatment Program at the
      Royal Prince Alfred Hospital in Sydney, Australia) and 33 healthy controls
      completed the Childhood Maltreatment Questionnaire, Lifetime Trauma Survey, and
      Perceived Levels of Stress Scale. The patient group reported significantly
      greater childhood trauma severity, more incidences of lifetime trauma, and higher
      perceived stress than controls. Logistic regression analyses indicated that the
      severity of childhood trauma was more strongly associated with addiction status
      than perceived stress. A greater number of lifetime trauma incidence was the best
      predictor of addiction. Contrary to expectations, noninterpersonal lifetime
      trauma was a better predictor of addiction status than was interpersonal lifetime
      trauma. Results suggest that lifetime trauma and childhood trauma may play an
      important factor in opioid addiction over what can be accounted for by stress.

PMID- 29569990
TI  - Molecular neuroimaging in primary progressive aphasia with predominant agraphia.
AB  - A 62-year-old male presented with progressive isolated writing and spelling
      difficulties. Neurological, neuropsychological, speech, and language evaluations
      identified only minimal additional abnormalities. The presenting characteristics
      did not meet criteria for any particular variant of primary progressive aphasia;
      his clinical presentation is best described as primary progressive aphasia, with
      a predominant, almost pure agraphia. Brain MRI showed asymmetric, bilateral
      parenchymal volume loss, with left hippocampal atrophy. Fluorodeoxyglucose-F18
      positron emission tomography showed hypometabolism in the lateral left frontal
      lobe, including Exner's area. Beta-amyloid and tau-positron emission tomography
      scans were negative, indicating the etiology was not Alzheimer's disease. The
      underlying neurodegenerative process is most likely related to TDP-43, although a
      4-repeat tauopathy cannot be excluded. Following his clinical evolution, and
      ultimately identifying the underlying pathology from autopsy, will elucidate the
      etiology of this interesting clinical presentation.

PMID- 29569992
TI  - Revisiting Factors Associated With Screen Time Media Use: A Structural Study
      Among School-Aged Adolescents.
AB  - BACKGROUND: Screen-based media overuse has been related to harmful consequences
      especially among children and adolescents. Given their complex
      interrelationships, predictors of screen time (ST) should be analyzed
      simultaneously rather than individually to avoid incomplete conclusions. METHODS:
      Structural equation models were conducted to examine associations between media
      ST (television, video games, and computers) along with harmful consequences in
      adolescents' well-being, such as underweight and overweight, depression, and
      school failure. Predictors included individual (gender, age, and physical
      activity), family (structure and socioeconomic background), and substance use
      variables. We used the Health Behaviour in School-aged Children survey organized
      in 2014, including eighth- and ninth-grade students living in France (N = 3720).
      RESULTS: Students reported spending 3 hours per day in front of each media.
      Spending more than 2 hours behind each of those 3 media was associated with lower
      life satisfaction, less physical activity, active school bullying, and grade
      repetition. Socioeconomic status was the most important predictor of ST, whereas
      regular substance uses showed modest associations. CONCLUSION: The main
      implication of our findings is to sensitize parents and stakeholders about the
      limitation of ST, including their own use that adolescents are likely to mimic.
      Alternative measures such as off-line time should be encouraged.

PMID- 29569993
TI  - Deaths after feeding-tube withdrawal from patients in vegetative and minimally
      conscious states: A qualitative study of family experience.
AB  - BACKGROUND: Families of patients in vegetative or minimally conscious states are
      often horrified by the suggestion of withdrawing a feeding tube, even when they
      believe that their relative would not have wanted to be maintained in their
      current condition. Very little is known about what it is like to witness such a
      death. AIM: To understand these families' experience of their relatives' deaths.
      DESIGN: Qualitative study using in-depth narrative interviews analyzed
      inductively with thematic analysis. PARTICIPANTS: A total of 21 people (from 12
      families) whose vegetative or minimally conscious relative died following court
      authorized withdrawal of artificial nutrition and hydration. All had supported
      treatment withdrawal. FINDINGS: Interviewees were usually anxious in advance
      about the nature of the death and had sometimes confronted resistance from, and
      been provided with misinformation by, healthcare staff in long-term care
      settings. However, they overwhelmingly described deaths as peaceful and sometimes
      even as a "good death." There was (for some) a significant "burden of witness"
      associated with the length of time it took the person to die and/or distressing
      changes in their appearance. Most continued to voice ethical objections to the
      manner of death while considering it "the least worst" option in the
      circumstances. CONCLUSION: Staff need to be aware of the distinctive issues
      around care for this patient group and their families. It is important to
      challenge misinformation and initiate honest discussions about feeding-tube
      withdrawal and end-of-life care for these patients. Families (and staff) need
      better support in managing the "burden of witness" associated with these deaths.

PMID- 29569994
TI  - Video observations of maternal sensitivity in urban and rural Iran.
AB  - There is evidence that rural versus urban residence is a salient factor in
      predicting parenting practices. In what is most likely the very first video
      observation study of parenting ever to come out of Iran, mothers and their 18-60
      month-old children were observed for 30 min of free interaction at their homes in
      urban (n = 11) and rural (n = 15) Iran. None of the mothers made any comments
      about being filmed, none expressed insecurities about what to do, and only four
      mothers looked at the camera more than once or twice. Compared to rural mothers,
      urban mothers showed significantly higher levels of verbal expression, warmth,
      and doing chores as an activity during the observations. However, this did not
      translate to significant group differences mothers in sensitivity, non
      interference, and general involvement with the child. The discussion focuses on
      different modalities of expressing sensitivity in urban versus rural mothers in
      Iran.

PMID- 29569996
TI  - Adults Engaged in Sports in Early Life Have Higher Bone Mass Than Their Inactive
      Peers.
AB  - PURPOSE: To analyze the relationship between engagement in sports in early life
      and bone variables among adults of both sexes. METHODS: The sample was composed
      of 225 men and women. Demographic data were collected, and dual-energy X-ray
      absorptiometry was used to assess bone mineral density, bone mineral content, and
      lean soft tissue. Sports participation in early life was assessed by an interview
      including childhood and adolescence. Consumption of tobacco and alcohol was also
      assessed by interview and the habitual physical activity level by a pedometer.
      RESULTS: Inactive men had bone mineral content around 11% lower than active men
      in childhood or adolescence, whereas for women, this difference represented
      around 14%. Active men had 74% less fat mass than inactive men in early life, and
      the difference was 67% for women. Early sports participation explained the
      differences in whole-body bone mineral content (16.8%, P-value = .005) and bone
      mineral density (8.8%, P-value = .015), as well as bone mineral density in lower
      limbs (18.9%, P-value = .001) among women. CONCLUSION: Adults engaged in sports
      in early life have higher bone mass than their inactive peers, especially women.

PMID- 29569997
TI  - Patterns of Physical Activity and Screen Time Among Brazilian Children.
AB  - OBJECTIVE: To investigate the patterns of physical activity (PA) and screen time
      among children and adolescents attended by the Brazilian National Health System.
      METHODS: This cross-sectional study was conducted in the city of Bauru, Sao
      Paulo, Brazil. The sample was composed of 270 children and adolescents attending
      5 basic health care units. PA and screen time were assessed through a
      questionnaire. Economic status, sex, and body composition variables were used as
      covariates. RESULTS: Boys were more likely to be active when compared with girls
      (odds ratio = 2.56; 95% confidence interval, 1.43-4.58). Children and adolescents
      who accumulated less screen time were more likely to be in the most active group
      (odds ratio = 0.41; 95% confidence interval, 0.24-0.72). When comparing data year
      on year, we found that the level of PA has not changed significantly among
      children aged 7-10 years; however, at the age of 10, we noticed a significant
      reduction in PA scores, which kept decreasing until the age of 12. Regarding
      screen time, the situation was the opposite, with the amount of time spent in
      this behavior increasing over the years. CONCLUSION: Our results showed an
      association between low PA levels and high amount of screen time among children
      and adolescents, showing that is necessary to encourage an active lifestyle,
      decreasing time spent on television, computers, cell phones, and video games.

PMID- 29569995
TI  - Phosphorylation and interactions associated with the control of the Leishmania
      Poly-A Binding Protein 1 (PABP1) function during translation initiation.
AB  - The Poly-A Binding Protein (PABP) is a conserved eukaryotic polypeptide involved
      in many aspects of mRNA metabolism. During translation initiation, PABP interacts
      with the translation initiation complex eIF4F and enhances the translation of
      polyadenylated mRNAs. Schematically, most PABPs can be divided into an N-terminal
      RNA-binding region, a non-conserved linker segment and the C-terminal MLLE
      domain. In pathogenic Leishmania protozoans, three PABP homologues have been
      identified, with the first one (PABP1) targeted by phosphorylation and shown to
      co-immunoprecipitate with an eIF4F-like complex (EIF4E4/EIF4G3) implicated in
      translation initiation. Here, PABP1 phosphorylation was shown to be linked to
      logarithmic cell growth, reminiscent of EIF4E4 phosphorylation, and coincides
      with polysomal association. Phosphorylation targets multiple serine-proline (SP)
      or threonine-proline (TP) residues within the PABP1 linker region. This is an
      essential protein, but phosphorylation is not needed for its association with
      polysomes or cell viability. Mutations which do impair PABP1 polysomal
      association and are required for viability do not prevent phosphorylation,
      although further mutations lead to a presumed inactive protein largely lacking
      phosphorylated isoforms. Co-immunoprecipitation experiments were carried out to
      investigate PABP1 function further, identifying several novel protein partners
      and the EIF4E4/EIF4G3 complex, but no other eIF4F-like complex or subunit. A
      novel, direct interaction between PABP1 and EIF4E4 was also investigated and
      found to be mediated by the PABP1 MLLE binding to PABP Interacting Motifs (PAM2)
      within the EIF4E4 N-terminus. The results shown here are consistent with
      phosphorylation of PABP1 being part of a novel pathway controlling its function
      and possibly translation in Leishmania.

PMID- 29569998
TI  - The use of behavioural theories in end-of-life care research: A systematic
      review.
AB  - BACKGROUND: It is necessary to understand behaviours that contribute to
      improvement in the quality of end-of-life care; use of behavioural theories
      allows identification of factors underlying end-of-life care behaviour, but
      little is known about the extent to which, and in what manner, these theories are
      used in an end-of-life care research context. AIM: To assess the number of end-of
      life care studies that have used behavioural theories, which theories were used,
      to what extent main constructs were explored/measured and which behavioural
      outcomes were examined. DESIGN: We conducted a systematic review. The protocol
      was registered on PROSPERO (CRD42016036009). DATA SOURCES: The MEDLINE (PubMed),
      PsycINFO, EMBASE, Web of Science and CINAHL databases were searched from
      inception to June 2017. We included studies aimed at understanding or changing
      end-of-life care behaviours and that explicitly referred to individual
      behavioural theories. RESULTS: We screened 2231 records by title and abstract,
      retrieved 43 full-text articles and included 31 studies - 27 quantitative (of
      which four (quasi-)randomised controlled trials) and four qualitative - for data
      extraction. More than half used the Theory of Planned Behaviour (9), the Theory
      of Reasoned Action (4) or the Transtheoretical Model (8). In 9 of 31 studies, the
      theory was fully used, and 16 of the 31 studies focussed on behaviours in advance
      care planning. CONCLUSION: In end-of-life care research, the use of behavioural
      theories is limited. As many behaviours can determine the quality of care, their
      more extensive use may be warranted if we want to better understand and influence
      behaviours and improve end-of-life care.

PMID- 29569999
TI  - Independent Associations and Interactions of Perceived Neighborhood and
      Psychosocial Constructs on Adults' Physical Activity.
AB  - BACKGROUND: Neighborhood and psychosocial variables are related to physical
      activity (PA), yet interactions between these factors in predicting PA are
      infrequently studied. METHODS: This analysis examines the independent
      associations and interactions between self-reported neighborhood and psychosocial
      variables in relation to moderate to vigorous PA (MVPA) among adults from a US
      panel sample. RESULTS: In adjusted models, neighborhood social capital was
      positively associated with meeting MVPA guidelines. Fewer barriers, greater self
      efficacy, and greater autonomous motivation also corresponded with greater odds
      of meeting MVPA guidelines. An interaction between social capital and autonomous
      motivation showed that social capital was only associated with MVPA when
      autonomous motivation was high. Participants who reported both high autonomous
      motivation and high social capital were most likely to meet MVPA guidelines.
      CONCLUSIONS: Neighborhood social capital, barriers, self-efficacy, and autonomous
      motivation may be important correlates in promoting adults' PA. Future directions
      include using objective neighborhood and PA data in similar analyses and
      investigating associations of neighborhood and psychosocial variables with
      multiple PA activities. Intervention research to promote PA should also examine
      whether effects of interventions targeting psychosocial constructs are moderated
      by features of an individual's neighborhood or whether perceived social capital
      can be addressed in interventions in conjunction with psychosocial variables.

PMID- 29570000
TI  - Assessment of peanut allergen Ara h1 in processed foods using a SWCNTs-based
      nanobiosensor.
AB  - The goals of this research were to develop a rapid single-walled carbon nanotube
      (SWCNT)-based biosensor and to employ it to commercial food products for Ara h1
      detection. The SWCNT-based biosensor was fabricated with SWCNTs immobilized with
      antibody (pAb) through hybridization of 1-pyrenebutanoic acid succinimidyl ester
      (1-PBASE) as a linker. The resistance difference (DeltaR) was calculated by
      measuring linear sweep voltammetry (LSV) using a potentiostat. Resistance values
      increased as the concentration of Ara h1 increased over the range of 1 to 105
      ng/L. The specific binding of anti-Ara h1 pAb to antigen including Ara h1 was
      confirmed by both indirect ELISA kit and biosensor assay. The biosensor was
      exposed to extracts prepared from commercial processed food containing peanuts,
      or no peanuts, and could successfully distinguish the peanut containing foods. In
      addition, the application of present biosensor approach documented the precise
      detection of Ara h1 concentrations in commercially available peanut containing
      foods.

PMID- 29570001
TI  - Do Not Forget About Public Transportation: Analysis of the Association of Active
      Transportation to School Among Washington, DC Area Children With Parental
      Perceived Built Environment Measures.
AB  - BACKGROUND: Although the active transportation (AT) indicator received an F grade
      on the 2016 US Report Card on Physical Activity for Children and Youth, this AT
      assessment excluded public transportation. An objective of the Built Environment
      and Active Play Study was to assess youth AT, including public transportation,
      among Washington, DC area children in relation to parental perceptions of
      neighborhood built environment (BE) variables. METHODS: Questionnaires were
      mailed to 2000 parents of children aged 7-12 years. AT to school (ATS) was
      assessed with the question: "In an average school week, how many days does your
      child use each of the following ways to get to and from school? (a) Walk; (b)
      Bike; (c) Car; (d) Bus or Metro." Parental perceived BE data were obtained
      through questionnaire items, and logistic regression was conducted to determine
      if BE variables were associated with youth ATS. RESULTS: The sample included 144
      children (50% female; average age 9.7 years; 56.3% white; 23.7% African American;
      10.4% Asian American). Over 30% used ATS-public transportation 5 days per week,
      and nearly 13% used ATS-walking daily. Parental perceived BE variables
      significantly predicted youth ATS-walking and ATS-public transportation.
      CONCLUSIONS: ATS-public transportation is common among Washington, DC area youth,
      and parental perceptions of BE can significantly predict ATS.

PMID- 29570002
TI  - Accelerometry-Derived Physical Activity Correlations Between Parents and Their
      Fourth-Grade Child Are Specific to Time of Day and Activity Level.
AB  - BACKGROUND: The purpose of this study was to employ high-frequency accelerometry
      to explore parent-child physical activity (PA) relationships across a free-living
      sample. METHODS: We recorded 7 days of wrist-mounted accelerometry data from 168
      dyads of elementary-aged children and their parents. Using a custom MATLAB
      program (Natick, MA), we summed child and parent accelerations over 1 and 60
      seconds, respectively, and applied published cut points to determine the amount
      of time spent in moderate-vigorous PA (MVPA). Bivariate and partial correlations
      examined parent-child relationships between percentage of time spent in MVPA.
      RESULTS: Weak to moderate positive correlations were observed before school (r =
      .326, P < .001), after school (r = .176, P = .023), during the evening (r = .213,
      P = .006), and on weekends (r = .231, P = .003). Partial correlations controlling
      for parent-child MVPA revealed significant relationships during the school day (r
      = .185, P = .017), before school (r = .315, P < .001), and on weekends (r = .266,
      P = .001). In addition, parents of more active children were significantly more
      active than parents of less active children during the evening. CONCLUSIONS:
      These data suggest that there is some association between parent-child PA,
      especially before school and on weekends. Future interventions aiming to increase
      PA among adults and children must consider patterns of MVPA specific to children
      and parents and target them accordingly.

PMID- 29570003
TI  - Economic Evaluation of Global Endometrial Ablation Versus Inpatient and
      Outpatient Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial
      and Medicaid Payer Perspectives.
AB  - Every year, abnormal uterine bleeding (AUB) exacts a heavy toll on women's health
      and leads to high costs for the US health care system. The literature shows that
      endometrial ablation results in fewer complications, shorter recovery and lower
      costs than more commonly performed hysterectomy procedures. The objective of this
      study was to model clinical-economic outcomes, budget impact, and cost
      effectiveness of global endometrial ablation (GEA) versus outpatient hysterectomy
      (OPH) and inpatient hysterectomy (IPH) procedures. A decision tree, state
      transition (semi-Markov) economic model was developed to simulate 3 hypothetical
      cohorts of women who received surgical treatment for AUB (GEA, OPH, and IPH) over
      1, 2, and 3 years to evaluate clinical and economic outcomes for GEA vs. OPH and
      GEA vs. IPH. Two versions of the model were created to reflect both commercial
      health care payer and US Medicaid perspectives, and analyses were conducted for
      both payer types. Total health care costs in the first year after GEA were
      substantially lower compared with those for IPH and OPH. Budget impact analysis
      results showed that increasing GEA utilization yields total annual cost savings
      of about $906,000 for a million-member commercial health plan and about $152,000
      in cost savings for a typical-sized state Medicaid plan with 1.4 million members.
      Cost-effectiveness analysis results for both perspectives showed GEA as
      economically dominant (conferring greater benefit at lower cost) over both OPH
      and IPH in the 1-year commercial scenario. This study demonstrates that, for some
      patients, GEA may prove to be a safe, uterus-sparing, cost-effective alternative
      to OPH and IPH for the surgical treatment of AUB.

PMID- 29570004
TI  - Demographics and clinical characteristics of episodic hypothermia in multiple
      sclerosis.
AB  - BACKGROUND: Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The
      putative mechanism is impairment of thermoregulation due to a presumed
      demyelinating hypothalamic lesion. OBJECTIVE: To describe a cohort of patients
      with MS, who developed EH. METHODS: Patients were identified through review of
      the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were
      [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within
      any field. We reviewed records for accuracy of diagnoses and abstracted relevant
      data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic
      lesions. RESULTS: Of 156 patients, 34 had concurrent MS and hypothermia. Thirty
      two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years,
      and median expanded disability status scale (EDSS) was 8.0. Most patients
      presented with alterations in consciousness. Infection was suspected as the
      precipitating factor in 19 (56%), but clinically/laboratory supported in only 9
      (28%). MRI lesions were evident within the hypothalamus in only 4 (14%).
      CONCLUSION: EH occurs predominantly in patients with advanced secondary
      progressive MS. The major manifestation is altered consciousness. Infection is
      often suspected as causal, but infrequently confirmed. Although commonly
      implicated, hypothalamic lesions were rarely evident on MRI and were absent in
      two post-mortem evaluations.

PMID- 29570005
TI  - Can a Lifestyle Intervention Increase Active Transportation in Women Aged 55-70
      years? Secondary Outcomes From a Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Physical activity confers many health benefits to older adults, and
      adopting activity into daily life routines may lead to better uptake. The purpose
      of this study was to test the effect of a lifestyle intervention to increase
      daily physical activity in older women through utilitarian walking and use of
      public transportation. METHODS: In total, 25 inactive women with mean age (SD) of
      64.1 (4.6) years participated in this pilot randomized controlled trial
      [intervention (n = 13) and control (n = 12)]. Seven-day travel diaries (trips per
      week) and the International Physical Activity Questionnaire (minutes per week)
      were collected at baseline, 3, and 6 months. RESULTS: At 3 months, intervention
      participants reported 9 walking trips per week and 643.5 minutes per week of
      active transportation, whereas control participants reported 4 walking trips per
      week and 49.5 minutes per week of active transportation. Adjusting for baseline
      values, there were significant group differences favoring Everyday Activity
      Supports You for walking trips per week [4.6 (0.5 to 9.4); P = .04] and active
      transportation minutes per week [692.2 (36.1 to 1323.5); P = .05]. At 6 months,
      significant group differences were observed in walking trips per week [6.1 (1.9
      to 11.4); P = .03] favoring the intervention (9 vs 2 trips per week). CONCLUSION:
      Given these promising findings, the next step is to test Everyday Activity
      Supports You model's effectiveness to promote physical activity in older women
      within a larger study.

PMID- 29570006
TI  - Use of the Apollo detachable-tip microcatheter for endovascular embolization of
      arteriovenous malformations and arteriovenous fistulas.
AB  - OBJECTIVE Liquid embolic agents have revolutionized endovascular management of
      arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs).
      Nonetheless, since 2005, the US FDA has received more than 100 reports of
      microcatheter breakage or entrapment related to Onyx embolization, including 9
      deaths. In 2014, the Apollo detachable-tip microcatheter became the first of its
      kind available in the US. Since then, few reports on its safety have been
      published. METHODS The authors conducted a retrospective review of endovascular
      cases by searching the patient databases at 2 tertiary cerebrovascular centers
      (Barrow Neurological Institute and University of Pittsburgh Medical Center).
      Patients who underwent endovascular embolization of an AVM or AVF using the
      Apollo microcatheter were identified. Patient demographics and lesion
      characteristics were collected. The authors analyzed Apollo-specific endovascular
      variables, such as number of microcatheterizations, sessions, and pedicles
      embolized; microcatheter tip detachment status; obliteration rate; and
      endovascular- and microcatheter-related morbidity and mortality. RESULTS From
      July 2014 to October 2016, a total of 177 embolizations using the Apollo
      microcatheter were performed in 61 patients (mean age 40.3 years). The most
      frequent presentation was hemorrhage (22/61, 36.1%). Most lesions were AVMs
      (51/61, 83.6%; mean diameter 30.6 mm). The mean Spetzler-Martin grade was 2.4.
      Thirty-nine (76.5%) of 51 patients with AVMs underwent resection.
      Microcatheterization was successful in 172 pedicles. Most patients (50/61, 82%)
      underwent a single embolization session. The mean number of pedicles per session
      was 2.5 (range 1-7). Onyx-18 was used in 103 (59.9%), N-butyl cyanoacrylate
      (NBCA) in 44 (25.6%), and Onyx-34 in 25 (14.5%) of the 172 embolizations. In
      45.9% (28/61) of the patients, lesion obliteration of 75% or greater was
      achieved. Tip detachment occurred in 19.2% (33/172) of microcatheters. Fifty
      three (86.9%) of the 61 patients who underwent embolization with the Apollo
      microcatheter had good functional outcomes (modified Rankin Scale score 0-2). No
      unintended microcatheter fractures or related morbidity was observed. One patient
      died of intraprocedural complications unrelated to microcatheter selection. In
      the univariate analysis, microcatheter tip detachment (p = 0.12), single
      embolized pedicles (p = 0.12), and smaller AVM nidus diameter (p = 0.17)
      correlated positively with high obliteration rates (> 90%). In the multivariate
      analysis, microcatheter tip detachment was the only independent variable
      associated with high obliteration rates (OR 9.5; p = 0.03). CONCLUSIONS The use
      of the Apollo detachable-tip microcatheter for embolization of AVMs and AVFs is
      associated with high rates of successful catheterization and obliteration and low
      rates of morbidity and mortality. The microcatheter was retrieved in all cases,
      even after prolonged injections in distal branch pedicles, often with significant
      reflux. This study represents the largest case series on the application of the
      Apollo microcatheter for neurointerventional procedures.

PMID- 29570007
TI  - Superiority of constructive interference in steady-state MRI sequencing over T1
      weighted MRI sequencing for evaluating cavernous sinus invasion by pituitary
      macroadenomas.
AB  - OBJECTIVE Preoperatively determining the extent of parasellar invasion of
      pituitary macroadenomas is useful for surgical planning and patient counseling.
      Here, the authors compared constructive interference in steady state (CISS), a T2
      weighted gradient-echo MRI sequence, to volume-interpolated breath-hold
      examination (VIBE), a T1-weighted gradient-echo MRI sequence, for evaluation of
      cavernous sinus invasion (CSI) by pituitary macroadenomas. METHODS VIBE and CISS
      images of 98 patients with pituitary macroadenoma were retrospectively analyzed
      and graded using the modified Knosp classification. The Knosp grades were
      correlated to surgical findings of CSI, which were determined intraoperatively
      using 0 degrees  and 30 degrees  endoscopes. The predictive accuracies for CSI
      according to the Knosp grades derived from the CISS and VIBE images were compared
      using receiver operating characteristic (ROC) curves. Postoperative MRI was used
      to evaluate the gross-total resection (GTR) rates. RESULTS The CSI rate by
      pituitary macroadenomas was 27.6% (27 of 98 cases). Of 196 assessments (left and
      right sides of 98 macroadenomas), 45 (23.0%) had different Knosp grades when
      scored using VIBE versus CISS images. For the VIBE images, 0% of Knosp grade 0,
      4.5% of grade 1, 23.8% of grade 2, 42.1% of grade 3A, 100% of grade 3B, and 83.3%
      of grade 4 macroadenomas were found to have CSI intraoperatively. For the CISS
      images, 0% of Knosp grade 0, 2.1% of grade 1, 31.3% of grade 2, 56.3% of grade
      3A, 100% of grade 3B, and 100% of grade 4 macroadenomas were found to have CSI
      intraoperatively. Two pituitary macroadenomas were classified as grade 4 on VIBE
      sequences but grades 3A and 2 on CISS sequences; CSI was not observed
      intraoperatively in both cases. The GTR rate was 64.3% and 60.0% for high-grade
      (3A, 3B, and 4) macroadenomas classified using VIBE and CISS sequences,
      respectively. The areas under the ROC curves were 0.94 and 0.97 for VIBE- and
      CISS-derived Knosp grades (p = 0.007), respectively. CONCLUSIONS Knosp grades
      determined using CISS sequence images are better correlated with intraoperative
      CSI than those determined using VIBE sequence images. CISS sequences may be
      valuable for the preoperative assessment of pituitary macroadenomas.

PMID- 29570008
TI  - Intraoperative use of transcranial motor/sensory evoked potential monitoring in
      the clipping of intracranial aneurysms: evaluation of false-positive and false
      negative cases.
AB  - OBJECTIVE Somatosensory and motor evoked potentials (SEPs and MEPs) are often
      used to prevent ischemic complications during aneurysm surgeries. However,
      surgeons often encounter cases with suspicious false-positive and false-negative
      results from intraoperative evoked potential (EP) monitoring, but the incidence
      and possible causes for these results are not well established. The aim of this
      study was to investigate the efficacy and reliability of EP monitoring in the
      microsurgical treatment of intracranial aneurysms by evaluating false-positive
      and false-negative cases. METHODS From January 2012 to April 2016, 1514 patients
      underwent surgery for unruptured intracranial aneurysms (UIAs) with EP monitoring
      at the authors' institution. An EP amplitude decrease of 50% or greater compared
      with the baseline amplitude was defined as a significant EP change. Correlations
      between immediate postoperative motor weakness and EP monitoring results were
      retrospectively reviewed. The authors calculated the sensitivity, specificity,
      and positive and negative predictive values of intraoperative MEP monitoring, as
      well as the incidence of false-positive and false-negative results. RESULTS
      Eighteen (1.19%) of the 1514 patients had a symptomatic infarction, and 4 (0.26%)
      had a symptomatic hemorrhage. A total of 15 patients showed motor weakness, with
      the weakness detected on the immediate postoperative motor function test in 10 of
      these cases. Fifteen false-positive cases (0.99%) and 8 false-negative cases
      (0.53%) were reported. Therefore, MEP during UIA surgery resulted in a
      sensitivity of 0.10, specificity of 0.94, positive predictive value of 0.01, and
      negative predictive value of 0.99. CONCLUSIONS Intraoperative EP monitoring has
      high specificity and negative predictive value. Both false-positive and false
      negative findings were present. However, it is likely that a more meticulously
      designed protocol will make EP monitoring a better surrogate indicator of
      possible ischemic neurological deficits.

PMID- 29570009
TI  - Improvement in cognitive function after surgery for low-grade glioma.
AB  - OBJECTIVE Cognition is a key component in health-related quality of life (HRQoL)
      and is currently incorporated as a major parameter of outcome assessment in
      patients treated for brain tumors. The effect of surgery on cognition and HRQoL
      remains debatable. The authors investigated the impact of resection of low-grade
      gliomas (LGGs) on cognition and the correlation with various histopathological
      markers. METHODS A retrospective analysis of patients with LGG who underwent
      craniotomy for tumor resection at a single institution between 2010 and 2014 was
      conducted. Of 192 who underwent resective surgery for LGG during this period, 49
      had complete pre- and postoperative neurocognitive evaluations and were included
      in the analysis. These patients completed a full battery of neurocognitive tests
      (memory, language, attention and working memory, visuomotor organization, and
      executive functions) pre- and postoperatively. Tumor and surgical characteristics
      were analyzed, including volumetric measurements and histopathological markers
      (IDH, p53, GFAP). RESULTS Postoperatively, significant improvement was found in
      memory and executive functions. A subgroup analysis of patients with dominant
      side tumors, most of whom underwent intraoperative awake mapping, revealed
      significant improvement in the same domains. Patients whose tumors were on the
      nondominant side displayed significant improvement only in memory functions.
      Positive staining for p53 testing was associated with improved language function
      and greater extent of resection in dominant-side tumors. GFAP positivity was
      associated with improved memory in patients whose tumors were on the nondominant
      side. No correlation was found between cognitive outcome and preoperative tumor
      volume, residual volume, extent of resection, or IDH1 status. CONCLUSIONS
      Resection of LGG significantly improves memory and executive function and thus is
      likely to improve functional outcome in addition to providing oncological
      benefit. GFAP and pP53 positivity could possibly be associated with improved
      cognitive outcome. These data support early, aggressive, surgical treatment of
      LGG.

PMID- 29570010
TI  - Longitudinal anterior-to-posterior shift of collateral channels in patients with
      moyamoya disease: an implication for its hemorrhagic onset.
AB  - OBJECTIVE This study aimed to assess longitudinal changes in the collateral
      channels originating from the lenticulostriate artery (LSA), posterior
      communicating artery (PCoA), and anterior and posterior choroidal arteries (AChA
      and PChA, respectively) during disease progression and/or aging. The impact of
      collateral channels on onset type was also examined. METHODS This study included
      71 involved hemispheres in 41 patients with moyamoya disease. The disease was
      categorized into 6 stages according to Suzuki's angiographic staging system. The
      degree of development of each moyamoya vessel was categorized into 3 grades.
      RESULTS The LSA started to dilate in stage 2, showed the most prominent
      development in stage 3, and decreased in more advanced stages (p < 0.001). The
      AChA most notably developed in stage 3 and gradually shrank (p = 0.04). The PCoA
      started to dilate in stage 3 and showed the most prominent development in stage 4
      (p = 0.03). The PChA started to dilate in stage 3 and showed the most prominent
      development in stages 4 to 5 (p < 0.001). Patient age was negatively related to
      LSA development (p = 0.01, R = 0.30) and was positively associated with the
      abnormal dilation and extension of the PCoA (p = 0.02, R = 0.28) and PChA (p <
      0.001, R = 0.45). The PCoA, AChA, and PChA more distinctly developed in
      hemispheres with intracerebral or intraventricular hemorrhage than in hemispheres
      with ischemic stroke or transient ischemic attack (p < 0.001, p = 0.03, and p =
      0.03, respectively). CONCLUSIONS This study suggests that the collateral channels
      through moyamoya vessels longitudinally shift from the anterior to posterior
      component during disease progression and aging, which may be closely related to
      the onset of hemorrhagic stroke in adult moyamoya disease.

PMID- 29570011
TI  - Clipping as re-treatment strategy after treatment of a cerebral aneurysm with the
      Woven EndoBridge embolization device: case report.
AB  - Recently, treatment of cerebral aneurysms with the Woven EndoBridge (WEB) device
      has become an established endovascular strategy. However, over time,
      neurosurgeons and neuroradiologists will be confronted with the challenge of how
      to treat aneurysm recanalization. The authors report the case of a 49-year-old
      woman who underwent re-treatment with clipping after the recanalization of a 4 *
      3-mm anterior communicating artery aneurysm that had previously been treated
      using a 4 * 3 WEB device. In contrast to the authors' prior experiences with
      clipping of previously coiled aneurysms, the WEB device was found to have a
      responsive softness during clip placement, and the aneurysm was more
      maneuverable. Moreover, evaluation with indocyanine green angiography was easy to
      perform because of the transparent mesh of the WEB device. No profound scarring
      or WEB protrusion was noted during surgery, making the procedure easier and less
      dangerous with regard to additional complications. The authors suggest that re
      treatment via clipping should be considered in select cases of aneurysm
      recurrence after treatment with an intraaneurysmal flow diverter.

PMID- 29570012
TI  - Validation of diffusion tensor imaging tractography to visualize the
      dentatorubrothalamic tract for surgical planning.
AB  - OBJECTIVE The dentatorubrothalamic tract (DRTT) has been suggested as the
      anatomical substrate for deep brain stimulation (DBS)-induced tremor alleviation.
      So far, little is known about how accurately and reliably tracking results
      correspond to the anatomical DRTT. The objective of this study was to
      systematically investigate and validate the results of different tractography
      approaches for surgical planning. METHODS The authors retrospectively analyzed 4
      methodological approaches for diffusion tensor imaging (DTI)-based fiber tracking
      using different regions of interest in 6 patients with essential tremor. Tracking
      results were analyzed and validated with reference to MRI-based anatomical
      landmarks, were projected onto the stereotactic atlas of Morel at 3 predetermined
      levels (vertical levels -3.6, -1.8, and 0 mm below the anterior commissure
      posterior commissure line), and were correlated to clinical outcome. RESULTS The
      4 different methodologies for tracking the DRTT led to divergent results with
      respect to the MRI-based anatomical landmarks and when projected onto the
      stereotactic atlas of Morel. There was a statistically significant difference in
      the lateral and anteroposterior coordinates at the 3 vertical levels (p < 0.001,
      2-way ANOVA). Different fractional anisotropy values ranging from 0.1 to 0.46
      were required for anatomically plausible tracking results and led to varying
      degrees of success. Tracking results were not correlated to postoperative tremor
      reduction. CONCLUSIONS Different tracking methods can yield results with good
      anatomical approximation. The authors recommend using 3 regions of interest
      including the dentate nucleus of the cerebellum, the posterior subthalamic area,
      and the precentral gyrus to visualize the DRTT. Tracking results must be
      cautiously evaluated for anatomical plausibility and accuracy in each patient.

PMID- 29570013
TI  - Value of pituitary gland MRI at 7 T in Cushing's disease and relationship to
      inferior petrosal sinus sampling: case report.
AB  - Cushing's disease is caused by adrenocorticotrophic hormone (ACTH)-secreting
      pituitary adenomas, which are often difficult to identify on standard 1.5-T or 3
      T MRI, including dynamic contrast imaging. Inferior petrosal and cavernous sinus
      sampling remains the gold standard for MRI-negative Cushing's disease. The
      authors report on a 27-year-old woman with Cushing's disease in whom the results
      of standard 1.5-T and 3-T MRI, including 1.5-T dynamic contrast imaging, were
      negative. Inferior petrosal sinus sampling showed a high central-to-peripheral
      ACTH ratio (148:1) as well as a right-to-left ACTH gradient (19:1), suggesting a
      right-sided pituitary microadenoma. The patient underwent 7-T MRI, which showed
      evidence of a right-sided pituitary lesion with focal hypoenhancement not
      visualized on 1.5-T or 3-T MRI. The patient underwent an endoscopic endonasal
      transsphenoidal operation, with resection of a right-sided pituitary mass.
      Postoperatively, she developed clinical symptoms suggestive of adrenal
      insufficiency and a nadir cortisol level of 1.6 MUg/dl on postoperative day 3,
      and hydrocortisone therapy was initiated. Permanent histopathology specimens
      showed Crooke's hyaline change and ACTH-positive cells suggestive of an adenoma.
      MRI at 7 T may be beneficial in identifying pituitary microadenoma location in
      cases of standard 1.5-T and 3-T MRI-negative Cushing's disease. In the future, 7
      T MRI may preempt inferior petrosal sinus sampling and help in cases of standard
      and dynamic contrast 1.5-T and 3-T MRI-negative Cushing's disease.

PMID- 29570014
TI  - Letter to the Editor. Intraoperative aneurysm rupture during awake clipping of
      cerebral aneurysms.

PMID- 29570016
TI  - Early and middle childhood developmental, cognitive, and psychiatric outcomes of
      Malawian children affected by retinopathy positive cerebral malaria.
AB  - The objective is to determine the short -and long-term developmental, cognitive,
      and psychiatric effects of retinopathy positive cerebral malaria (CM-R) among
      young children in a prospective study assessing them around the onset of disease
      and again 2 years at preschool and again at school age. In total, 109 children
      were recruited from the Queen Elizabeth Central Hospital in Blantyre, Malawi, (N
      = 49) with CM-R and non-malaria controls  (N = 60). Children were assessed for
      overall motor, language, and social skills using the Malawi Developmental
      Assessment Tool (MDAT) at preschool age. At school age, the same children were
      then given the Kaufman Assessment Battery for Children, second edition (KABC-II),
      which assessed global cognitive performancememory, and learning; as well as the
      Test of Variables of Attention (TOVA), which assessed attention. The Achenbach
      Child Development Checklist (CBCL) was administered at both time points to assess
      emotional and behavioral patterns. Controls scored significantly better on all
      KABC-II global domains as well as on the mental processing index than their CM-R
      group counterparts, but showed no performance differences in the TOVA and CBCL
      assessments at school age, or in the MDAT and CBCL assessments at preschool age.
      The MDAT total score was significantly correlated with the KABC-II sequential
      processing, learning, and mental processing index among CM-R survivors but not
      among controls. Persisting neurocognitive effects of CM can be captured with the
      KABC-II at school age. The MDAT at preschool age is correlated with the KABC-II
      among CM-R survivors and can be used to capture early emerging developmental
      deficits due to CM-R.

PMID- 29570017
TI  - Age at death of major cardiovascular diseases in 13 cohorts. The seven countries
      study of cardiovascular diseases 45-year follow-up.
AB  - OBJECTIVES: To explore age at death (AD) for major cardiovascular diseases (CVD)
      and their risk factors in originally middle-aged men followed nearly to
      extinction in the Seven Countries Study. MATERIALS AND METHODS: Thirteen cohorts
      of men aged 40-59 years (N = 10,628) in seven countries (USA, Finland, the
      Netherlands, Italy, Serbia, Greece, Japan) were enrolled in late 1950s and early
      1960s and were followed 45 years for mortality. AD was computed for coronary
      heart disease (CHD), stroke (STR), heart disease of uncertain aetiology (HDUE)
      and for all-causes. AD was compared across CHD-HDUE-STR. Cox models were computed
      for each end-point using baseline age, cigarettes smoking, systolic blood
      pressure and serum cholesterol. RESULTS: After 45 years 92.9% of men had died.
      The most common CVD death was CHD in most cohorts except some Mediterranean and
      Japanese cohorts where STR or HDUE were most prevalent. In 13 cohorts mean AD was
      74.5, 73.5, 75.7 and 79.1 years, respectively, for all-cause, CHD, STR and HDUE
      mortality (all possible differences were significant). The difference, across
      cohorts, between the highest and the lowest mean AD was 12.9, 9.0 and 4.7 years
      for CHD, HDUE and STR mortality, respectively. Risk factors explored were
      significant predictors of all three CVD end-points, except serum cholesterol,
      specific to CHD mortality. CONCLUSIONS: AD is a useful indicator of previous
      health and aging populations. STR and HDUE are diseases appearing later in life,
      thus being associated with a higher AD compared with CHD mortality.

PMID- 29570018
TI  - Preventive Use of a Resin-based Desensitizer Containing Glutaraldehyde on Tooth
      Sensitivity Caused by In-office Bleaching: A Randomized, Single-blind Clinical
      Trial.
AB  - OBJECTIVE: To evaluate the risk and intensity of bleaching-induced tooth
      sensitivity (TS) after in-office bleaching following topical application of a
      resin-based glutaraldehyde desensitizer. METHODS: Thirty-three patients were
      randomly assigned to the experimental (Gluma Desensitizer Liquid, Heraeus Kulzer,
      Hanau, Germany) and placebo groups. The placebo or Gluma Desensitizer Liquid was
      applied for one minute prior to application of an in-office bleaching gel.
      Bleaching was performed with 35% hydrogen peroxide gel (three applications * 15
      minutes each) over two sessions, one week apart. The color of the anterior teeth
      was evaluated before and 21 days after treatment using the VITA Classical shade
      guide, Bleachedguide 3D, and Easyshade spectrophotometer. TS during and after the
      bleaching was recorded according to the visual analog (VAS) and numerical rating
      (NRS) scales. All data were submitted to statistical analysis (alpha=0.05).
      RESULTS: There was no significant difference in absolute risk or intensity of TS
      between the two groups (risk and VAS, p=0.93 and 0.31, respectively; NRS,
      p>=0.45). At the end of the bleaching protocol, tooth whitening was observed in
      both groups, as evident from color change in shade guide units (DeltaSGU, 4.1
      7.1; both guides) and overall color change (DeltaE, 7.4-9.3 units); however,
      there were no significant differences in whitening between the two groups (
      p>0.11). CONCLUSION: Gluma Desensitizer Liquid was not able to reduce the risk or
      intensity of TS. Bleaching efficacy was not affected by application of the
      desensitizer.

PMID- 29570019
TI  - Effect of Various Bleaching Agents on the Surface Composition and Bond Strength
      of a Calcium Silicate-based Cement.
AB  - This study aimed to evaluate the morphological and elemental changes that occur
      on the surface of calcium silicate-based cement (CSC) and to analyze the bond
      strength of composite resin to CSC after application of various bleaching agents.
      One hundred twenty-five CSC blocks (Biodentine) were prepared and randomly
      divided into five groups according to the bleaching agent applied over the
      material surface (n=25): SP-DW (sodium perborate-distilled water mixture), SP-HP
      (sodium perborate-3% hydrogen peroxide [H2O2] mixture), CP (37% carbamide
      peroxide gel), HP (35% H2O2 gel), and a control group (no bleaching agent). After
      1 week, scanning electron microscopy provided an analysis of the surface
      morphology and elemental composition for 10 specimens from each group. Composite
      resin was placed at the center of each cement surface in the remaining specimens
      (n=15). A universal testing machine determined shear bond strength (SBS) and
      fracture patterns were identified with a dental operating microscope. Data were
      analyzed using one-way analysis of variance and Tukey HSD tests. The cement
      surface in the CP and HP groups presented changes in structure and elemental
      distribution compared with the remaining groups. The former groups exhibited a
      decrease in the calcium level and an increase in the silicon level and presented
      significantly fewer SBS values than the remaining groups ( p<0.05). Most failures
      were adhesive in the CP and HP groups, while they were predominantly cohesive in
      the remaining groups. The bleaching agents with higher concentration induced
      deterioration of the cement surface and negatively affected the bond strength of
      the composite resin to CSC. The use of CSC is recommended as a cervical barrier
      when intracoronal bleaching is performed with a mixture of sodium perborate with
      water or 3% H2O2.

PMID- 29570020
TI  - Nanofilled Resin Composite Properties and Clinical Performance: A Review.
AB  - The aim of this review was to compile recent evidence related to nanofilled resin
      composite materials regarding the properties and clinical performance. Special
      attention was given to mechanical properties, such as strength, hardness,
      abrasive wear, water sorption, and solubility. The clinical performance of
      nanocomposite materials compared with hybrid resin composites was also addressed
      in terms of retention and success rates, marginal adaptation, color match, and
      surface roughness. A search of English peer-reviewed dental literature (2003
      2017) from PubMed and MEDLINE databases was conducted using the terms
      "nanocomposites" or "nanofilled resin composite" and "clinical evaluation." The
      list was screened, and 82 papers that were relevant to the objectives of this
      work were included in the review. Mechanical properties of nanocomposites are
      generally comparable to those of hybrid composites but higher than microfilled
      composites. Nanocomposites presented lower abrasive wear than hybrids but higher
      sorption values. Their clinical performance was comparable to that of hybrid
      composites.

PMID- 29570021
TI  - Effect of Resin-modified Glass Ionomer Cement Dispensing/Mixing Methods on
      Mechanical Properties.
AB  - STATEMENT OF THE PROBLEM: Resin-modified glass ionomer cements (RMGIs) are often
      used for luting indirect restorations. Hand-mixing traditional cements demands
      significant time and may be technique sensitive. Efforts have been made by
      manufacturers to introduce the same cement using different dispensing/mixing
      methods. It is not known what effects these changes may have on the mechanical
      properties of the dental cement. PURPOSE: The purpose of this study was to
      evaluate the mechanical properties (diametral tensile strength [DTS], compressive
      strength [CS], and fracture toughness [FT]) of RMGIs with different
      dispensing/mixing systems. METHODS AND MATERIALS: The RMGI specimens (n=14)-RelyX
      Luting (hand mix), RelyX Luting Plus (clicker-hand mix), RelyX Luting Plus
      (automix) (3M ESPE), GC Fuji PLUS (capsule-automix), and GC FujiCEM 2 (automix)
      (GC)-were prepared for each mechanical test and examined after thermocycling
      (n=7/subgroup) for 20,000 cycles to the following: DTS, CS (ISO 9917-1) and FT
      (ISO standard 6872; Single-edge V-notched beam method). Specimens were mounted
      and loaded with a universal testing machine until failure occurred. Two-/one-way
      analysis of variance followed by Tukey honestly significantly different post hoc
      test was used to analyze data for statistical significance ( p<0.05). RESULTS:
      The interaction effect of both dispensing/mixing method and thermocycling was
      significant only for the CS test of the GC group ( p<0.05). The different
      dispensing/mixing methods had no effect on the DTS of the tested cements. The CS
      of GC Fuji PLUS was significantly higher than that of the automix version (
      p<0.05). The FT decreased significantly when switching from RelyX (hand mix) to
      RelyX Luting Plus (clicker-hand mix) and to RelyX Luting Plus (automix) (
      p<0.05). Except in the case of the DTS of the GC group and the CS of GC Fuji
      PLUS, thermocycling had a significant effect reducing the mechanical properties
      of the RMGI cements ( p<0.05). CONCLUSIONS: Introducing alternative
      dispensing/mixing methods for mixing RMGIs to reduce time and technique
      sensitivity may affect mechanical properties and is brand dependent.

PMID- 29570022
TI  - Do Nanofilled/Nanohybrid Composites Allow for Better Clinical Performance of
      Direct Restorations Than Traditional Microhybrid Composites? A Systematic Review.
AB  - This systematic review was carried out to assess the clinical effectiveness of
      nanofilled and nanohybrid composites used for direct restorations in comparison
      with microhybrid composites. The guidelines for the preferred reporting items for
      systematic reviews and meta-analyses were followed. A search of articles
      published from July 1996 to February 2017 was performed in PubMed, SciVerse
      Scopus, Latin American and Caribbean Health Sciences, the Scientific Electronic
      Library Online, and the Cochrane Library. The present review selected only
      randomized controlled trials comparing the clinical performance of a nanofilled
      or nanohybrid composite for direct restorations with that of a microhybrid
      composite. The research found 201 studies. Twenty-one articles fulfilled the
      criteria of the present review. However, the included studies were characterized
      by great methodological diversities. As a general trend, nanofilled and
      nanohybrid composites were found to be capable of clinical performance, marginal
      quality, and resistance to wear similar to that of traditional composites without
      showing improved surface characteristics. The risk of bias of included studies
      was judged unclear or high. The clinical performance of nanofilled/nanohybrid
      composites was found to be comparable to that of traditional composites in the
      posterior area. The data concerning anterior and cervical restorations were
      insufficient. With regard to the esthetic properties, there is a compelling need
      for studies on anterior teeth in which the operators are kept unaware of the
      restorative material. Nanofilled/nanohybrid composites seem to be a valid
      alternative to traditional microhybrid composites, and at the moment, there is
      low-level evidence attesting a lack of their superiority.

PMID- 29570023
TI  - Efficacy of Modern Light Curing Units in Polymerizing Peripheral Zones in
      Simulated Large Bulk-fill Resin-composite Fillings.
AB  - The variation in micro-hardness (HV) within simulated large cavities (10 * 6 mm)
      filled in one increment with three bulk-fill resin-based composites (BF-RBC) was
      assessed by means of a universal hardness device. Modern blue and violet-blue
      light curing units (LCUs) were applied in three different positions, by rotating
      the LCU in 120 degrees  steps. The exposure distance was 3 mm. One center and two
      peripheral (4-mm apart from the center) HV line profiles were measured in 0.5-mm
      steps at 24 hours postpolymerization to calculate the depth of cure (DOC).
      Incident light, irradiance, and spectral distribution were recorded. A
      multivariate analysis (general linear model) assessed the effect of the varied
      parameters as well as their interaction terms on HV and DOC. The effect of LCU
      rotation was not significant ( p=0.109). The DOC varied between 3.46 mm and 5.50
      mm and was more strongly influenced by the BF-RBC ( p<0.001, etaP2=0.774),
      followed by the width of specimen ( p<0.001, etaP2=0.554), while the influence of
      the LCU was very low ( p<0.06, etaP2=0.070). Whether a BF-RBC filling is cured as
      well in the periphery as in the center depends more on the material than on the
      curing unit used.

PMID- 29570025
TI  - Effect of Tooth-Whitening Procedures on Stained Composite Resins.
AB  - In this laboratory study, a composite resin was stained to a visibly discernible
      level using both coffee and red wine over 14 days (change was considered
      clinically noticeable and significant when DeltaEab*>=2.7). Color change was
      measured at one, three, seven, and 14 days of staining. Although the nature of
      color change was different for the two staining solutions, the overall degree of
      staining (DeltaEab*) rendered by either coffee or wine at each time interval was
      not significantly different ( p>=0.05). Four whitening protocols were applied to
      stained composites. Treatment included applications of distilled water (control),
      Crest Pro-Health [HD] toothpaste, Crest Whitestrips, Opalescence PF bleach (15%),
      and application of a fine pumice polishing (Preppies). HD toothpaste and
      Whitestrips were applied daily for 21 days, Opalescence was applied daily for 10
      days, and polishing was applied once. Each of the whitening products, applied in
      a manner simulating at-home or in-office treatment, was effective in producing
      color improvements (lightening) over controls ( p<0.05), but none of the four
      treatments produced lightening that was significantly different from the other
      treatments ( p>=0.05). A comparison of final composite color with that measured
      at baseline showed that Opalescence returned composite color to an acceptable
      level following exposure to both staining solutions (DeltaEab*<2.7), Whitestrips
      returned color close to baseline for wine-stained composites, and HD paste and
      polishing permitted residual stain to remain (DeltaEab*>=2.7).

PMID- 29570024
TI  - Effect of Mold Type and Diameter on the Depth of Cure of Three Resin-Based
      Composites.
AB  - OBJECTIVE: To evaluate the effects of different mold materials, their diameters,
      and light-curing units on the mechanical properties of three resin-based
      composites (RBC). METHODS AND MATERIALS: A conventional nano-filled resin
      composite (Filtek Supreme Ultra, 3M Oral Care, St Paul, MN, USA) and two bulk
      fill composites materials, Tetric Evoceram Bulk fill (Ivoclar Vivadent, Schaan,
      Liechtenstein) and Aura Bulk Fill (SDI, Bayswater, VIC, Australia), were tested.
      A total of 240 specimens were fabricated using metal or white semitransparent
      Delrin molds that were 4 or 10 mm in diameter. The RBCs were light cured for 40
      seconds on the high-power setting of either a monowave (DeepCure-S, 3M Oral Care)
      or polywave (Bluephase G2, Ivoclar Vivadent) light-emitting diode (LED) curing
      unit. The depth of cure was determined using a scraping test, according to the
      2009 ISO 4049 test method. Data were analyzed using multivariate analysis of
      variance followed by Tukey multiple comparison test ( p<0.05). RESULTS: In
      general, when used for 40 seconds, both LED curing lights achieved the same depth
      of cure ( p=0.157). However, the mold material and its diameter had a significant
      effect on the depth of cure of all three RBCs ( p<0.0001). CONCLUSION: Curing
      with either the polywave or monowave LED curing light resulted in the same depth
      of cure in the composites. The greatest depth of cure was always achieved using
      the 10-mm-diameter Delrin mold. Of the three RBCs tested, both Tetric Bulk Fill
      and Aura achieved a 4-mm depth of cure when tested in the 10-mm-diameter metal
      mold. Tetric Bulk Fill was the most transparent and had the greatest depth of
      cure, and the conventional composite had the least depth of cure. Very little
      violet (<420 nm) light penetrated through 6 mm of any of the RBCs.

PMID- 29570026
TI  - Influence of Surface Treatment on Composite Adhesion in Noncarious Cervical
      Lesions: Systematic Review and Meta-analysis.
AB  - The purpose of this study was to analyze the influence of dentin surface
      treatments on the retention rate of resin composite restorations in non-carious
      cervical lesions (NCCLs). Seven randomized clinical trials were included in this
      review. Data regarding retention rate, type of surface treatment, and the main
      characteristics of studies were analyzed. Two reviewers performed a literature
      search up to December 2016 in eight databases: PubMed (Medline), Lilacs, Ibecs,
      Web of Science, BBO, Scopus, Scielo and The Cochrane Library. Only clinical
      trials evaluating dentin surface treatments in resin composite restoration in
      NCCLs were included. Noncontrolled clinical trials, reviews, editorial letters,
      case reports, case series and studies published in a language other than English,
      Portuguese, or Spanish were not included. The included studies evaluated
      different surface treatments, such as using an adhesive system with a frictional
      technique, drying the dentin, and removing sclerotic dentin by using a bur and
      applying EDTA before primer use. The analysis considering the mechanical removal
      of dentin surface with a bur and the application of an adhesive system in a
      frictional mode showed these treatments improved retention rates of the resin
      composite restorations in NCCLs ( p<0.05). There is evidence in the literature
      suggesting that the mechanical removal of dentin surface with a bur and the
      application of an adhesive system in a frictional mode could improve the
      retention rates of resin composite restorations in NCCLs. However, the studies
      showed high heterogeneity, and additional clinical trials are needed to determine
      the best dentin treatment option in NCCLs.

PMID- 29570028
TI  - Use of a Modified Matrix Band Technique to Restore Subgingival Root Caries.
AB  - Given the increasing incidence of root caries in the elderly population,
      clinicians frequently must isolate and restore subgingival preparations. This
      article demonstrates a technique utilizing a modified Tofflemire matrix band that
      creates a preparation free of crevicular fluid and blood for restoration with
      resin-modified glass ionomer cement.

PMID- 29570027
TI  - High Bond Durability of Universal Adhesives on Glass Ceramics Facilitated by
      Silane Pretreatment.
AB  - OBJECTIVE:: This study aimed to investigate the long-term effectiveness of
      ceramic-resin bonding with universal adhesives in non-silane-pretreated and
      silane-pretreated modes after 10,000 cycles of thermal aging. METHODS AND
      MATERIALS:: All Bond Universal, Adhese Universal, Clearfil Universal Bond, and
      Single Bond Universal were selected. Etched lithium disilicate glass ceramics
      were prepared, randomly assigned to groups, and pretreated with or without
      ceramic primer containing silane coupling agent prior to the application of
      universal adhesive (ie, silane-pretreated or non-silane-pretreated mode). The
      shear bond strength (SBS), microleakage, and field-emission scanning electron
      microscopy images of the ceramic-resin interfaces were examined after 24 hours of
      water storage or 10,000 thermal cycles. Light microscopy and confocal laser
      scanning microscopy (CLSM) were performed to analyze marginal sealing ability.
      RESULTS:: SBS and microleakage percentage were significantly affected by bonding
      procedure (non-silane-pretreated or silane-pretreated mode) and aging (24 hours
      or 10,000 thermal cycles). After the universal adhesives in the non-silane
      pretreated mode were aged, SBS significantly decreased and microleakage
      percentage increased. By contrast, the SBS of Adhese Universal, Clearfil
      Universal Bond, and Single Bond Universal decreased, and the microleakage
      percentage of all of the adhesives increased in the silane-pretreated mode.
      However, after aging, the SBS of the silane-pretreated groups were higher and
      their microleakage percentages lower than those of the non-pretreated groups. In
      the non-silane-pretreated mode, adhesive failure was dominant and gaps between
      composite resin and the adhesive layer were significant when observed with CLSM.
      CONCLUSIONS:: The simplified procedure reduced the ceramic-resin bonding
      effectiveness of universal adhesives after aging, and additional silane
      pretreatment helped improve the long-term durability.

PMID- 29570029
TI  - Mini Fiberglass Post for Ankylosed Tooth Reconstruction: A Clinical Technique.
AB  - It was possible to restore the shape and function of a severely ankylosed tooth
      by fabricating a ceramic crown for placement on a resin reconstruction supported
      by mini fiberglass posts. By increasing the retention of the morphological
      reconstruction for the future support of indirect restorations, cementable
      intradentinal fiberglass posts enhance the longevity of these restorations.
      Ultimately, all proposals that seek to improve the long-term prognosis of
      restorations on ankylosed teeth, especially severely impacted ones, are of
      extreme clinical relevance.

PMID- 29570030
TI  - Novel Application of Skills for Psychological Recovery as an Early Intervention
      for Violent Loss: Rationale and Case Examples.
AB  - This article describes a novel application of Skills for Psychological Recovery
      (SPR)-a brief, early intervention developed by the National Center for
      Posttraumatic Stress Disorder and the National Child Traumatic Stress Network-for
      families grieving the violent death of a loved one. Drawing on conservation of
      resources theory, SPR incorporates cognitive-behavioral skills-building modules
      to help survivors cope with trauma-related distress and posttrauma resource loss.
      The authors describe the intervention and illustrate the use of SPR for violent
      loss by presenting data from two cases involving a suicide survivor and a
      homicide survivor. Implications for future research are discussed.

PMID- 29570031
TI  - Maternal Grief: A Qualitative Investigation of Mothers' Responses to the Death of
      a Child From Cancer.
AB  - This study explored bereaved mothers' responses to the death of a child from
      cancer, with a focus on identifying adaptive and complicated grief reactions. To
      understand the unique meaning of their loss, in-depth interviews were conducted
      with 13 mothers at two time points. Interpretative phenomenological analysis
      guided by meaning-making theories of loss-revealed five master categories: the
      perceptions of the child's life with cancer and death from the disease, changed
      self-identity, coping style, developing an ongoing relationship to the deceased
      child, and the postdeath social environment. Each of these master categories and
      associated subthemes provided insights into the characteristics of the bereaved
      mothers' adaptive and complicated grief responses to their loss. Given all the
      mothers evidenced multiple forms or types of these responses over time, they
      could not be categorized as adaptive or complicated grievers. However, the
      varying proportions of each of these responses highlighted differences in overall
      bereavement adaptation.

PMID- 29570032
TI  - Classroom-Based Physical Activity and Sedentary Behavior Interventions in
      Adolescents: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: It is reported that 81% of adolescents are insufficiently active.
      Schools play a pivotal role in promoting physical activity (PA) and reducing
      sedentary behavior (SB). The aim of this systematic review and meta-analysis was
      to evaluate classroom-based PA and SB interventions in adolescents. METHODS: A
      search strategy was developed using the Population Intervention Comparison
      Outcome Study (PICOS) design framework. Articles were screened using strict
      inclusion criteria. Study quality was assessed using the Effective Public Health
      Practice Project quality assessment tool ( http://www.ephpp.ca/tools.html ).
      Outcome data for preintervention and postintervention were extracted, and effect
      sizes were calculated using Cohen's d. RESULTS: The strategy yielded 7574
      potentially relevant articles. Nine studies were included for review. Study
      quality was rated as strong for 1 study, moderate for 5 studies, and weak for 3
      studies. Five studies were included for meta-analyses, which suggested that the
      classroom-based interventions had a nonsignificant effect on PA (P = .55, d =
      0.05) and a small, nonsignificant effect on SB (P = .16, d = -0.11). CONCLUSION:
      Only 9 relevant studies were found, and the effectiveness of the classroom-based
      PA and SB interventions varied. Based on limited empirical studies, there is not
      enough evidence to determine the most effective classroom-based methodology to
      increase PA and SB.

PMID- 29570033
TI  - Taking the next step in publication productivity analysis in pediatric
      neurosurgery.
AB  - OBJECTIVE There has been an increasing interest in the quantitative analysis of
      publishing within the field of neurosurgery at the individual, group, and
      institutional levels. The authors present an updated analysis of accredited
      pediatric neurosurgery training programs. METHODS All 28 Accreditation Council
      for Pediatric Neurosurgery Fellowship programs were contacted for the names of
      pediatric neurosurgeons who were present each year from 2011 through 2015.
      Faculty names were queried in Scopus for publications and citations during this
      time period. The 5-year institutional Hirsch index [i h(5)-index] and revised 5
      year institutional h-index [i r(5)-index] were calculated to rank programs. Each
      publication was reviewed to determine authorship value, tier of research,
      clinical versus basic science research, subject matter, and whether it was
      pediatrics-specific. A unique 3-tier article classification system was introduced
      to stratify clinical articles by quality and complexity, with tier 3 being the
      lowest tier of publication (e.g., case reports) and tier 1 being the highest
      (e.g., randomized controlled trials). RESULTS Among 2060 unique publications,
      1378 (67%) were pediatrics-specific. The pediatrics-specific articles had a mean
      of 15.2 citations per publication (median 6), whereas the non-pediatrics-specific
      articles had a mean of 23.0 citations per publication (median 8; p < 0.0001). For
      the 46% of papers that had a pediatric neurosurgeon as first or last author, the
      mean number of citations per publication was 12.1 (median 5.0) compared with 22.5
      (median 8.0) for those in which a pediatric neurosurgeon was a middle author (p <
      0.0001). Seventy-nine percent of articles were clinical research and 21% were
      basic science or translational research; however, basic science and translational
      articles had a mean of 36.9 citations per publication (median 15) compared with
      12.6 for clinical publications (median 5.0; p < 0.0001). Among clinical articles,
      tier 1 papers had a mean of 15.0 citations per publication (median 8.0), tier 2
      papers had a mean of 18.7 (median 8.0), and tier 3 papers had a mean of 7.8
      (median 3.0). Neuro-oncology papers received the highest number of citations per
      publication (mean 25.7). The most common journal was the Journal of Neurosurgery:
      Pediatrics (20%). MD/PhD faculty members had significantly more citations per
      publication than MD faculty members (mean 26.7 vs 14.0; p < 0.0001) and also a
      higher number of publications per author (mean 38.6 vs 20.8). The median i h(5)-
      and i r(5)-indices per program were 14 (range 5-48) and 10 (range 5.6-37.2),
      respectively. The mean i r(5)/i h(5)-index ratio was 0.8. The top 5 fellowship
      programs (in descending order) as ranked by the i h(5)-index corrected for number
      of faculty members were The Hospital for Sick Children, Toronto; Children's
      Hospital of Pittsburgh; University of California, San Francisco Benioff
      Children's Hospital; Seattle Children's Hospital; and St. Louis Children's
      Hospital. CONCLUSIONS About two-thirds of publications authored by pediatric
      neurosurgeons are pediatrics-specific, although non-pediatrics-specific articles
      averaged more citations. Most of the articles authored by pediatric neurosurgeons
      are clinical, with basic and translational articles averaging more citations.
      Neurosurgeons with PhD degrees averaged more total publications and more
      citations per publication. In all, this is the most advanced and informative
      analysis of publication productivity in pediatric neurosurgery to date.

PMID- 29570034
TI  - Split laminotomy versus conventional laminotomy: postoperative outcomes in
      pediatric patients.
AB  - OBJECTIVE Split laminotomy is a technique for accessing the spinal canal from the
      posterior midline that minimizes muscle dissection and bone removal. Benefits of
      this approach in minimizing postoperative pain and muscle atrophy in the adult
      population have been reported, but pediatric data are limited. Herein, the
      authors evaluate the benefits of the split laminotomy technique in pediatric
      patients. METHODS Data obtained in patients who underwent posterior spine surgery
      at Children's Hospital of Wisconsin for an intradural midline pathology between
      April 2008 and June 2015 were reviewed retrospectively. Each patient was assigned
      to one of two groups, the split-laminotomy or conventional-laminotomy group. The
      primary outcomes assessed were mean daily pain score, total opioid use over a
      period of 72 hours after surgery, and the degree of paraspinal muscle atrophy and
      fat infiltration found on short-term (1-4 months) and long-term (1-4 years)
      follow-up spine MRI studies. RESULTS A total of 117 patients underwent lumbar
      level surgery (83 conventional laminotomy, 34 split laminotomy), and 8 patients
      underwent thoracic-level surgery (4 in each group). No significant difference in
      the mean daily pain scores between groups was found. The daily opioid use was
      significantly lower in the split-laminotomy group on postoperative day 0 (POD0)
      and POD1 but not on POD2 (p = 0.01, 0.01, and 0.10, respectively). The total
      opioid use over the 72-hour postoperative period was significantly lower in the
      split-laminotomy group (p = 0.0008). The fat/muscle ratio was significantly
      higher in both the short-term and long-term follow-up periods in the conventional
      laminotomy group (p = 0.01 and 0.0002, respectively). The rate of change of
      paraspinal muscle fat infiltration was significantly lower in the split
      laminotomy group than in the conventional-laminotomy group (p = 0.007). The
      incidence of complications was not significantly different between groups (p =
      0.08). CONCLUSIONS This study was of the largest series reported thus far of
      pediatric patients who underwent split laminotomy and the only controlled study
      that has involved children. The authors' results reinforce the short-term benefit
      of split laminotomy in minimizing acute postoperative pain and long-term benefits
      of decreasing muscle atrophy and fatty degeneration, which are known to be
      associated with the development of chronic pain and spinal instability.
      Additional efforts for assessing long-term effects in the development of chronic
      pain, spinal instability, and spinal deformity are still necessary.

PMID- 29570035
TI  - Predictors of mortality in children with myelomeningocele and symptomatic Chiari
      type II malformation.
AB  - OBJECTIVE Chiari malformation type II (CM-II) in myelomeningocele is associated
      with a significant rate of mortality and poor outcome. Death is frequently
      heralded by the onset or progression of neurological symptoms. The authors sought
      to identify predictors of poor outcome and mortality within the myelomeningocele
      population at Children's Hospital of Pittsburgh. METHODS A retrospective chart
      and radiology review was performed on all infants who underwent primary closure
      of a myelomeningocele defect at Children's Hospital of Pittsburgh between the
      years of 1995 and 2015. Preoperative symptoms and signs leading to CM-II
      decompression, as well as operative details and postoperative changes in these
      symptoms and signs, were investigated in detail and correlated to outcome. Poor
      outcome was defined as death, stridor, or ventilator dependence. Deceased
      patients were separately assessed within this subgroup. RESULTS Thirty-two (21%)
      of 153 patients were found to have symptomatic CM-II. Of the 32 patients meeting
      inclusion criteria, 12 (38%) had poor outcomes. Eight patients (25%) died since
      initial presentation; 5 of these patients (16% of the overall cohort) died within
      the 1st year of life and 3 (9%) died during adolescence. Seven (88%) of the 8
      patients who died had central apnea on presentation (p = 0.001) and 7 (44%) of
      the 16 patients who developed symptoms in the first 3 months of life died,
      compared with 1 (6.3%) of 16 who developed symptoms later in childhood (p =
      0.04). The median Apgar score at 1 minute was 4.5 for patients who died and 8 for
      surviving patients (p = 0.006). The median diameter of the myelomeningocele
      defect was 5.75 cm for patients who died and 5 for those who survived (p = 0.01).
      The anatomical level of defect trended toward higher levels in patients who died,
      with 4 patients in that group having an anatomical level at L-2 or higher
      compared with 5 of the surviving patients (p = 0.001). The median initial head
      circumference for the 5 patients dying in the 1st year of life was 41.5 cm,
      versus 34 cm for all other patients (p = 0.01). CONCLUSIONS CM-II in spina bifida
      is associated with a significant mortality rate even when surgical intervention
      is performed. Death is more frequent in symptomatic patients presenting prior to
      1 year of age. Late deaths are associated with symptom progression despite
      aggressive surgical and medical intervention. In this patient cohort, death was
      more likely in patients with symptomatic presentation during the first 3 months
      of life, low Apgar scores, large myelomeningocele defects, early central apnea,
      and large head circumference at birth.

PMID- 29570037
TI  - Higher susceptibility to osmolality of the medaka (Oryzias latipes) mutants in
      orthologue genes of mammalian skin transglutaminases.
AB  - Transglutaminase (TG) is an essential enzyme to catalyze cross-linking reactions
      of epidermal proteins. Recently, we biochemically characterized human skin TG
      orthologues for medaka (Oryzias latipes), a model fish. By genome editing, gene
      modified fishes for the two orthologues were obtained, both of which lack the
      ordinal enzymes. These fish appeared to exhibit higher susceptibility to
      osmolality at the period of larvae.

PMID- 29570039
TI  - The Association of Health-Related Fitness and Chronic Absenteeism Status in New
      York City Middle School Youth.
AB  - BACKGROUND: Extensive research demonstrates the benefits of fitness on children's
      health and academic performance. Although decreases in health-related fitness may
      increase school absenteeism, multiple years of prospective, child-level data are
      needed to examine whether fitness changes predict subsequent chronic absenteeism
      status. METHODS: Six cohorts of New York City public school students were
      followed from grades 5-8 (2006/2007-2012/2013; N = 349,381). A longitudinal 3
      level logistic generalized linear mixed model with random intercepts was used to
      test the association of individual children's changes in fitness and 1-year
      lagged chronic absenteeism. RESULTS: The odds of chronic absenteeism increased
      27% [odds ratio (OR) 95% confidence interval (CI), 1.25-1.30], 15% (OR 95% CI,
      1.13-1.18), 9% (OR 95% CI, 1.07-1.11), and 1% (OR 95% CI, 0.98-1.04), for
      students who had a >20% decrease, 10%-20% decrease, <10% increase or decrease,
      and 10%-20% increase in fitness, respectively, compared with >20% fitness
      increase. CONCLUSION: These findings contribute important longitudinal evidence
      to a cross-sectional literature, demonstrating reductions in youth fitness may
      increase absenteeism. Given only 25% of youth aged 12-15 years achieve the
      recommended daily 60 minutes or more of moderate to vigorous physical activity,
      future work should examine the potential for youth fitness interventions to
      reduce absenteeism and foster positive attitudes toward lifelong physical
      activity.

PMID- 29570038
TI  - Endoplasmic reticulum stress epigenetics is related to adiposity, dyslipidemia,
      and insulin resistance.
AB  - Unresolved ER stress is involved in the onset and progression of several obesity
      related metabolic disorders, including dyslipidemia and insulin resistance.
      Different epigenetic modifications may regulate ER stress response and
      consequently disease risks. These epigenetic phenomena encompass DNA and histone
      methylation patterns in ER stress genes and downstream signaling molecules, as
      well as microRNA expression. Our results suggest potential associations of
      methylation signatures at ER regulatory genes in white blood cells with an
      abdominal/central obesity marker (waist circumference), dyslipidemia, and insulin
      resistance. Interestingly, most of these genes were implicated in ER stress, as
      revealed by pathway enrichment analysis. Together, these findings add knowledge
      into the current understanding of relationships between obesity and accompanying
      complications with epigenetics and ER stress. Here, we comment about the
      implication of ER stress in central/abdominal adiposity, dyslipidemia, and
      insulin resistance, with an emphasis on the role that epigenetics may play on
      these pathological processes.

PMID- 29570036
TI  - Anti-miRNA oligonucleotides: A comprehensive guide for design.
AB  - MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene
      expression post-transcriptionally. As a consequence of their function towards
      mRNA, miRNAs are widely associated with the pathogenesis of several human
      diseases, making miRNAs a target for new therapeutic strategies based on the
      control of their expression. Indeed, numerous works were published in the past
      decades showing the potential use of antisense oligonucleotides to target
      aberrant miRNAs (AMOs) involved in several human pathologies. New classes of
      chemical-modified-AMOs, including locked nucleic acid oligonucleotides, have
      recently proved their worth in silencing miRNAs. A correct design of a specific
      AMOs can help to improve their performance and potency towards the target miRNA
      by increasing for instance nuclease resistance and target affinity. This review
      outlines the technologies involved to suppress aberrant miRNAs. From the design
      strategies used in AMOs to its application in novel miRNA-based therapeutics and
      detection methodologies.

PMID- 29570040
TI  - Chemical warfare in Colombia, evidentiary ecologies and senti-actuando practices
      of justice.
AB  - Between 1994 and 2015, militarized aerial fumigation was a central component of
      US-Colombia antidrug policy. Crop duster planes sprayed a concentrated formula of
      Monsanto's herbicide, glyphosate, over illicit crops, and also forests, soils,
      pastures, livestock, watersheds, subsistence food and human bodies. Given that a
      national peace agreement was signed in 2016 between FARC-EP guerrillas and the
      state to end Colombia's over five decades of war, certain government officials
      are quick to proclaim aerial fumigation of glyphosate an issue of the past. Rural
      communities, however, file quejas (complaints or grievances) seeking compensation
      from the state for the ongoing effects of the destruction of their licit agro
      forestry. At the interfaces of feminist science and technology studies and
      anthropology, this article examines how evidentiary claims are mobilized when war
      deeply politicizes and moralizes technoscientific knowledge production. By
      ethnographically tracking the grievances filed by small farmers, I reveal the
      extent to which evidence circulating in zones of war - tree seedlings,
      subsistence crops, GPS coordinates and bureaucratic documents - retains (or not)
      the imprints of violence and toxicity. Given the systematic rejection of
      compensation claims, farmers engage in everyday material practices that attempt
      to transform chemically degraded ecologies. These everyday actualizations of
      justice exist both alongside and outside contestation over the geopolitically
      backed violence of state law. Rather than simply contrasting everyday acts of
      justice with denunciatory claims made against the state, farmers' reparative
      practices produce an evidentiary ecology that holds the state accountable while
      also ' senti-actuando' (feel-acting) alternative forms of justice.

PMID- 29570041
TI  - Percutaneous left atrial appendage occlusion in a lamin A/C gene mutation related
      cardiomyopathy patient with persistent left atrial appendage thrombus: a case
      report.

PMID- 29570042
TI  - Correlation between clinical variables and magnetic resonance imaging findings in
      symptomatic patients with chronic temporomandibular articular disc displacement
      with reduction: A retrospective analytical study.
AB  - Objective To correlate the clinical aspects of symptomatic patients with chronic
      articular disc displacement with reduction with alterations in the articular disc
      (AD) morphology and sagittal position. Methods Records from 109 patients were
      selected that included data on AD morphology and sagittal position as determined
      by MRI. According to the MRI results, the sagittal position and AD morphology
      with opened and closed mouth were correlated with many clinical variables.
      Results More than half of the patients studied were female, and the biconcave and
      hemiconvex morphologies were most common. Thirty-four patients (31.3%) presented
      with restricted maximum interincisal distance (MID). The biplanar morphology was
      associated with eccentric bruxism and MID (p < 0.05). Visual analog scale (VAS)
      scores between 2 and 7 were shown to be risk factors (p < 0.05). Conclusion The
      mouth position can influence AD morphology and eccentric bruxism. VAS scores and
      unknown etiology were risk factors.

PMID- 29570043
TI  - Developing a fatigue questionnaire for Chinese civil aviation pilots.
AB  - OBJECTIVE: To assess the fatigue risk is an important challenge in improving
      flight safety in the aviation industry. The aim of this study was to develop a
      comprehensive fatigue risk management indicators system and a fatigue
      questionnaire for Chinese civil aviation pilots. METHODS: Participants included
      74 civil aviation pilots (all males). They finished the questionnaire in 20 min
      before a flight mission. Estimation of internal consistency with Cronbach's alpha
      and Student's t test as well as Pearson's correlation analysis were the main
      statistical methods. RESULTS: The results revealed that the fatigue questionnaire
      had acceptable internal consistency reliability and construct validity; there
      were significant differences in fatigue scores between international and domestic
      flight pilots. Also, some international flight pilots, who had taken medications
      as a sleep aid, had worse sleep quality than those who had not. Long-endurance
      flights across time zones caused significant differences in circadian rhythm.
      CONCLUSIONS: The fatigue questionnaire can be used to measure Chinese civil
      aviation pilots' fatigue, which provides a reference for a fatigue risk
      management system for civil aviation pilots.

PMID- 29570044
TI  - Alteplase for the treatment of acute ischemic stroke in patients with low
      National Institutes of Health Stroke Scale and not clearly disabling deficits
      (Potential of rtPA for Ischemic Strokes with Mild Symptoms PRISMS): Rationale and
      design.
AB  - Rationale Over half of acute ischemic stroke patients have a low National
      Institutes of Health Stroke Scale of 0-5 and up to two-thirds may not appear
      clearly disabled at presentation. The efficacy of intravenous alteplase for the
      latter group is not known. Aim Potential of rtPA for Ischemic Strokes with Mild
      Symptoms (PRISMS) was designed to evaluate the safety and efficacy of intravenous
      alteplase for the treatment of acute ischemic stroke with National Institutes of
      Health Stroke Scale 0-5 and without clearly disabling deficits. Sample size
      estimates A maximum of 948 subjects were required to test the superiority
      hypothesis with 80% power, according to a one-sided 0.025 level of significance.
      Methods and design PRISMS was a multicenter, randomized, double-blind, placebo
      controlled phase 3b clinical trial. Patients were randomized to the active arm
      (intravenous alteplase standard dose of 0.9 mg/kg, up to a maximum of 90 mg, plus
      oral aspirin placebo) or the control arm (intravenous alteplase placebo plus
      active oral aspirin dose of 325 mg). Study outcome The primary efficacy endpoint
      was favorable functional outcome, defined as a modified Rankin Scale score 0 or 1
      assessed at 90-day postrandomization.

PMID- 29570045
TI  - Preoperative full-length standing radiographs and revision rates in lumbar
      degenerative scoliosis.
AB  - OBJECTIVE Full-length (36-inch) standing spine radiographs are commonly used by
      spine surgeons to evaluate patients with lumbar degenerative scoliosis (LDS).
      Despite this practice, the impact of these images on preoperative decision making
      and the rate of revision surgery has not been analyzed. The purpose of this study
      is to determine if preoperative full-length standing spine radiographs improve
      surgical decision making by decreasing the rate of revision surgery in patients
      with LDS. METHODS From the Health Care Service Corporation administrative claims
      database, the authors identified patients 50-80 years of age with LDS who had
      undergone surgery including posterior lumbar decompression and fusion over 2-6
      levels and with at least 5 years of continuous coverage after the index surgery.
      Patients were stratified into the following groups, according to the preoperative
      imaging studies performed within 6 months before their index surgery: lumbar
      spine MRI studies only, lumbar spine MRI studies and standard lumbar spine
      radiographs, CT myelograms, and full-length standing spine radiographs. Survival
      analysis was performed with the occurrence of a revision within 5 years of the
      index surgery as the outcome of interest. RESULTS A total of 411 patients were
      included in the study after applying the inclusion and exclusion criteria.
      Revision surgery within 5 years after the index procedure was most frequent in
      the patients with preoperative MRI only (41.8%), followed by the patients with a
      CT myelogram (30.4%) and those with MRI and standard radiographs (24.8%). The
      lowest revision rate was seen among those with long-cassette standing radiographs
      (11.1%). Patients whose preoperative evaluation included full-length standing
      radiographs (OR 0.353, p = 0.034) and MRI studies plus radiographs (OR 0.650, p =
      0.022) were less likely to require revision surgery at 5 years after the index
      procedure. CONCLUSIONS An assessment of standing alignment using full-length (36
      inch) standing radiographs may be beneficial in reducing the risk of revision
      surgery in patients with lumbar scoliosis. This observation was not limited to
      patients with large curves or substantial deformity.

PMID- 29570046
TI  - Sagittal radiographic parameters demonstrate weak correlations with pretreatment
      patient-reported health-related quality of life measures in symptomatic de novo
      degenerative lumbar scoliosis: a European multicenter analysis.
AB  - OBJECTIVE Previous studies have demonstrated that among patients with adult
      spinal deformity (ASD), sagittal plane malalignment is poorly tolerated and
      correlates with suboptimal patient-reported health-related quality of life
      (HRQOL). These studies included a broad range of radiographic abnormalities and
      various types of ASD. However, the clinical and radiographic characteristics of
      de novo degenerative lumbar scoliosis (DNDLS), a subtype of ASD, may influence
      previously reported correlation strengths. The aim of this study was to correlate
      sagittal radiographic parameters with pretreatment HRQOL in patients with
      symptomatic DNDLS. METHODS In this multicenter retrospective study of
      prospectively collected data, 74 patients with symptomatic DNDLS were enrolled
      based on anteroposterior and lateral 36-inch standing radiographs. Measurements
      included Cobb angle, coronal imbalance, pelvic incidence (PI), pelvic tilt (PT),
      lumbar lordosis (LL), sagittal vertical axis (SVA), thoracic kyphosis, pelvic
      incidence minus lumbar lordosis (PI-LL), T1-pelvic angle, and global tilt. HRQOL
      questionnaires included the Oswestry Disability Index (ODI), Scoliosis Research
      Society (SRS-22r), 36-item Short-Form Health Survey, and numeric rating scale
      (NRS) for back and leg pain. Correlations between radiographic parameters and
      HRQOL were assessed. Finally, HRQOL and increasing severity of sagittal modifiers
      (SVA, PI-LL, and PT) were evaluated. RESULTS Weak correlations were found between
      SVA and ODI (r = 0.296, p < 0.05) and PT with NRS back pain and the SRS pain
      domain (r = -0.260, p < 0.05, and r = 0.282, p < 0.05, respectively). Other
      sagittal radiographic parameters did not show any significant correlation with
      HRQOL. No significant differences in HRQOL were found concerning the increasing
      severity of PT, PI-LL, and SVA. CONCLUSIONS While DNDLS is a severe disabling
      condition, no noteworthy association between clinical and sagittal radiographic
      parameters was found through this study, demonstrating that sagittal radiographic
      parameters should not be considered the unique predictor of pretreatment
      suboptimal health status in this specific group of patients. Future studies
      addressing classification and treatment algorithms will have to take into account
      the existing subgroups of ASD.

PMID- 29570047
TI  - Painless motor radiculopathy of the cervical spine: clinical and radiological
      characteristics and long-term outcomes after operative decompression.
AB  - OBJECTIVE Various neurological diseases are known to cause progressive painless
      paresis of the upper limbs. In this study the authors describe the previously
      unspecified syndrome of compression-induced painless cervical radiculopathy with
      predominant motor deficit and muscular atrophy, and highlight the clinical and
      radiological characteristics and outcomes after surgery for this rare syndrome,
      along with its neurological differential diagnoses. METHODS Medical records of
      788 patients undergoing surgical decompression due to degenerative cervical spine
      diseases between 2005 and 2014 were assessed. Among those patients, 31 (3.9%,
      male to female ratio 4.8 to 1, mean age 60 years) presented with painless
      compressive cervical motor radiculopathy due to neuroforaminal stenosis without
      signs of myelopathy; long-term evaluation was available in 23 patients with 49
      symptomatic foraminal stenoses. Clinical, imaging, and operative findings as well
      as the long-term course of paresis and quality of life were analyzed. RESULTS
      Presenting symptoms (mean duration 13.3 months) included a defining progressive
      flaccid radicular paresis (median grade 3/5) without any history of radiating
      pain (100%) and a concomitant muscular atrophy (78%); 83% of the patients were
      smokers and 17% patients had diabetes. Imaging revealed a predominantly anterior
      nerve root compression at the neuroforaminal entrance in 98% of stenoses. Thirty
      stenoses (11 patients) were initially decompressed via an anterior surgical
      approach and 19 stenoses (12 patients) via a posterior surgical approach. Overall
      reoperation rate due to new or recurrent stenoses was 22%, with time to
      reoperation shorter in smokers (p = 0.033). Independently of the surgical
      procedure chosen, long-term follow-up (mean 3.9 years) revealed a stable or
      improved paresis in 87% of the patients (median grade 4/5) and an excellent
      general performance and quality of life. CONCLUSIONS Painless cervical motor
      radiculopathy predominantly occurs due to focal compression of the anterior nerve
      root at the neuroforaminal entrance. Surgical decompression is effective in
      stabilizing or improving motor function with a resulting favorable long-term
      outcome.

PMID- 29570048
TI  - Key drivers of patient satisfaction in lumbar spine surgery.
AB  - OBJECTIVE The Patient Experience of Care, composed of 9 dimensions derived from
      the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)
      survey, is being used by the Centers for Medicare & Medicaid Services to adjust
      hospital reimbursement. Currently, there are minimal data on how scores on the
      constituent HCAHPS items impact the global dimension of satisfaction, the Overall
      Hospital Rating (OHR). The purpose of this study was to determine the key drivers
      of overall patient satisfaction in the setting of inpatient lumbar spine surgery.
      METHODS Demographic and preoperative patient characteristics were obtained.
      Patients selecting a top-box score for OHR (a 9 or 10 of 10) were considered to
      be satisfied with their hospital experience. A baseline multivariable logistic
      regression model was then developed to analyze the association between patient
      characteristics and top-box OHR. Then, multivariable logistic regression models
      adjusting for patient-level covariates were used to determine the association
      between individual components of the HCAHPS survey and a top-box OHR. RESULTS A
      total of 453 patients undergoing lumbar spine surgery were included, 80.1% of
      whom selected a top-box OHR. Diminishing overall health status (OR 0.63, 95% CI
      0.43-0.91) was negatively associated with top-box OHR. After adjusting for
      potential confounders, the survey items that were associated with the greatest
      increased odds of selecting a top-box OHR were: staff always did everything they
      could to help with pain (OR 12.5, 95% CI 6.6-23.7), and nurses were always
      respectful (OR 11.0, 95% CI 5.3-22.6). CONCLUSIONS Patient experience of care is
      increasingly being used to determine hospital and physician reimbursement. The
      present study analyzed the key drivers of patient experience among patients
      undergoing lumbar spine surgery and found several important associations. Patient
      overall health status was associated with top-box OHR. After adjusting for
      potential confounders, staff always doing everything they could to help with pain
      and nurses always being respectful were the strongest predictors of overall
      satisfaction in this population. These findings highlight opportunities for
      quality improvement efforts in the spine care setting.

PMID- 29570049
TI  - Editorial. The relevance of sagittal radiographic parameters.

PMID- 29570050
TI  - Forniceal deep brain stimulation induces gene expression and splicing changes
      that promote neurogenesis and plasticity.
AB  - Clinical trials are currently underway to assess the efficacy of forniceal deep
      brain stimulation (DBS) for improvement of memory in Alzheimer's patients, and
      forniceal DBS has been shown to improve learning and memory in a mouse model of
      Rett syndrome (RTT), an intellectual disability disorder caused by loss-of
      function mutations in MECP2. The mechanism of DBS benefits has been elusive,
      however, so we assessed changes in gene expression, splice isoforms, DNA
      methylation, and proteome following acute forniceal DBS in wild-type mice and
      mice lacking Mecp2. We found that DBS upregulates genes involved in synaptic
      function, cell survival, and neurogenesis and normalized expression of ~25% of
      the genes altered in Mecp2-null mice. Moreover, DBS induced expression of 17-24%
      of the genes downregulated in other intellectual disability mouse models and in
      post-mortem human brain tissue from patients with Major Depressive Disorder,
      suggesting forniceal DBS could benefit individuals with a variety of
      neuropsychiatric disorders.

PMID- 29570051
TI  - The yeast H+-ATPase Pma1 promotes Rag/Gtr-dependent TORC1 activation in response
      to H+-coupled nutrient uptake.
AB  - The yeast Target of Rapamycin Complex 1 (TORC1) plays a central role in
      controlling growth. How amino acids and other nutrients stimulate its activity
      via the Rag/Gtr GTPases remains poorly understood. We here report that the signal
      triggering Rag/Gtr-dependent TORC1 activation upon amino-acid uptake is the
      coupled H+ influx catalyzed by amino-acid/H+ symporters. H+-dependent uptake of
      other nutrients, ionophore-mediated H+ diffusion, and inhibition of the vacuolar
      V-ATPase also activate TORC1. As the increase in cytosolic H+ elicited by these
      processes stimulates the compensating H+-export activity of the plasma membrane
      H+-ATPase (Pma1), we have examined whether this major ATP-consuming enzyme might
      be involved in TORC1 control. We find that when the endogenous Pma1 is replaced
      with a plant H+-ATPase, H+ influx or increase fails to activate TORC1. Our
      results show that H+ influx coupled to nutrient uptake stimulates TORC1 activity
      and that Pma1 is a key actor in this mechanism.

PMID- 29570052
TI  - Normal mitochondrial function in Saccharomyces cerevisiae has become dependent on
      inefficient splicing.
AB  - Self-splicing introns are mobile elements that have invaded a number of highly
      conserved genes in prokaryotic and organellar genomes. Here, we show that
      deletion of these selfish elements from the Saccharomyces cerevisiae
      mitochondrial genome is stressful to the host. A strain without mitochondrial
      introns displays hallmarks of the retrograde response, with altered mitochondrial
      morphology, gene expression and metabolism impacting growth and lifespan.
      Deletion of the complete suite of mitochondrial introns is phenocopied by
      overexpression of the splicing factor Mss116. We show that, in both cases,
      abnormally efficient transcript maturation results in excess levels of mature cob
      and cox1 host mRNA. Thus, inefficient splicing has become an integral part of
      normal mitochondrial gene expression. We propose that the persistence of S.
      cerevisiae self-splicing introns has been facilitated by an evolutionary lock-in
      event, where the host genome adapted to primordial invasion in a way that
      incidentally rendered subsequent intron loss deleterious.

PMID- 29570053
TI  - The NIH must reduce disparities in funding to maximize its return on investments
      from taxpayers.
AB  - New data from the NIH reveal that the scientific return on its sponsored research
      reaches a maximum at around $400,000 of annual support per principal
      investigator. We discuss the implications of this 'sweet spot' for funding
      policy, and propose that the NIH should limit both the minimum and maximum amount
      of funding per researcher.

PMID- 29570054
TI  - Optimization-Based Image Reconstruction From Low-Count, List-Mode TOF-PET Data.
AB  - OBJECTIVE: We investigate an optimization-based approach to image reconstruction
      from list-mode data in digital time-of-flight (TOF) positron emission tomography
      (PET) imaging. METHOD: In the study, the image to be reconstructed is designed as
      a solution to a convex, non-smooth optimization program, and a primal-dual
      algorithm is developed for image reconstruction by solving the optimization
      program. The algorithm is first applied to list-mode TOF-PET data of a typical
      count level from physical phantoms and a human subject. Subsequently, we explore
      the algorithm's potential for image reconstruction in low-dose and/or fast TOF
      PET imaging of practical interest by applying the algorithm to list-mode TOF-PET
      data of different, low-count levels from the same physical phantoms and human
      subject. RESULTS: Visual inspection and quantitative-metric analysis reveal that
      the optimization reconstruction approach investigated can yield images with
      enhanced spatial and contrast resolution, suppressed image noise, and increased
      axial volume coverage over the reference images obtained with a standard clinical
      reconstruction algorithm especially for low-dose TOF-PET data. SIGNIFICANCE: The
      optimization-based reconstruction approach can be exploited for yielding insights
      into potential quality upper bound of reconstructed images in, and design of
      scanning protocols of, TOF-PET imaging of practical significance.

PMID- 29570055
TI  - A Low-Power Current-Reuse Analog Front-End for High-Density Neural Recording
      Implants.
AB  - Studying brain activity in vivo requires collecting bioelectrical signals from
      several microelectrodes simultaneously in order to capture neuron interactions.
      In this work, we present a new current-reuse analog front-end (AFE), which is
      scalable to very large numbers of recording channels, thanks to its small
      implementation silicon area and its low-power consumption. This current-reuse
      AFE, which is including a low-noise amplifier (LNA) and a programmable gain
      amplifier (PGA), employs a new fully differential current-mirror topology using
      fewer transistors, and improving several design parameters, such as power
      consumption and noise, over previous current-reuse amplifier circuit
      implementations. We show that the proposed current-reuse amplifier can provide a
      theoretical noise efficiency factor (NEF) as low as 1.01, which is the lowest
      reported theoretical NEF provided by an LNA topology. A foue-channel current
      reuse AFE implemented in a CMOS 0.18-MUm technology is presented as a proof-of
      concept. T-network capacitive circuits are used to decrease the size of input
      capacitors and to increase the gain accuracy in the AFE. The measured performance
      of the whole AFE is presented. The total power consumption per channel, including
      the LNA and the PGA stage, is 9 MUW (4.5 MUW for LNA and 4.5 MUW for PGA), for an
      input referred noise of 3.2 MUVrms, achieving a measured NEF of 1.94. The entire
      AFE presents three selectable gains of 35.04, 43.1, and 49.5 dB, and occupies a
      die area of 0.072 mm2 per channel. The implemented circuit has a measured inter
      channel rejection ratio of 54 dB. In vivo recording results obtained with the
      proposed AFE are reported. It successfully allows collecting low-amplitude
      extracellular action potential signals from a tungsten wire microelectrode
      implanted in the hippocampus of a laboratory mouse.

PMID- 29570056
TI  - Ultracompact Implantable Design With Integrated Wireless Power Transfer and RF
      Transmission Capabilities.
AB  - This paper presents an ultracompact design of biomedical implantable devices with
      integrated wireless power transfer (WPT) and RF transmission capabilities for
      implantable medical applications. By reusing the spiral coil in an implantable
      device, both RF transmission and WPT are realized without the performance
      degradation of both functions in ultracompact size. The complete theory of WPT
      based on magnetic resonant coupling is discussed and the design methodology of an
      integrated structure is presented in detail, which can guide the design
      effectively. A system with an external power transmitter and implantable
      structure is fabricated to validate the proposed approach. The experimental
      results show that the implantable structure can receive power wirelessly at 39.86
      MHz with power transfer efficiency of 47.2% and can also simultaneously radiate
      at 2.45 GHz with an impedance bandwidth of 10.8% and a gain of -15.71 dBi in the
      desired direction. Furthermore, sensitivity analyses are carried out with the
      help of experiment and simulation. The results reveal that the system has strong
      tolerance to the nonideal conditions. Additionally, the specific absorption rate
      distribution is evaluated in the light of strict IEEE standards. The results
      reveal that the implantable structure can receive up to 115 mW power from an
      external transmitter and radiate 6.4 dB.m of power safely.

PMID- 29570058
TI  - A Five-Tissue-Layer Human Body Communication Circuit Model Tunable to Individual
      Characteristics.
AB  - Human body communication (HBC) has several advantages over traditional wireless
      communications due to the high conductivity of human body. An accurate body
      channel model plays a vital role in optimizing the performance and power of HBC
      transceivers. In this paper, we present a body channel model with three distinct
      features. First, it takes into account all five body tissue layers resulting
      better accuracy; second, it adapts to different individuals with the proposed
      layer thickness estimation technique; third, it counts in the variation of
      backward coupling capacitance versus different postures. These new features
      significantly improve the model accuracy. Measurement results show that the
      proposed model achieves a maximum error of 2.21% in path loss for different human
      subjects.

PMID- 29570057
TI  - Vital Sign Monitoring Through the Back Using an UWB Impulse Radar With Body
      Coupled Antennas.
AB  - Radar devices can be used in nonintrusive situations to monitor vital sign,
      through clothes or behind walls. By detecting and extracting body motion linked
      to physiological activity, accurate simultaneous estimations of both heart rate
      (HR) and respiration rate (RR) is possible. However, most research to date has
      focused on front monitoring of superficial motion of the chest. In this paper,
      body penetration of electromagnetic (EM) wave is investigated to perform back
      monitoring of human subjects. Using body-coupled antennas and an ultra-wideband
      (UWB) pulsed radar, in-body monitoring of lungs and heart motion was achieved. An
      optimised location of measurement in the back of a subject is presented, to
      enhance signal-to-noise ratio and limit attenuation of reflected radar signals.
      Phase-based detection techniques are then investigated for back measurements of
      vital sign, in conjunction with frequency estimation methods that reduce the
      impact of parasite signals. Finally, an algorithm combining these techniques is
      presented to allow robust and real-time estimation of both HR and RR. Static and
      dynamic tests were conducted, and demonstrated the possibility of using this
      sensor in future health monitoring systems, especially in the form of a smart car
      seat for driver monitoring.

PMID- 29570059
TI  - An Extreme Learning Machine-Based Neuromorphic Tactile Sensing System for Texture
      Recognition.
AB  - Despite significant advances in computational algorithms and development of
      tactile sensors, artificial tactile sensing is strikingly less efficient and
      capable than the human tactile perception. Inspired by efficiency of biological
      systems, we aim to develop a neuromorphic system for tactile pattern recognition.
      We particularly target texture recognition as it is one of the most necessary and
      challenging tasks for artificial sensory systems. Our system consists of a
      piezoresistive fabric material as the sensor to emulate skin, an interface that
      produces spike patterns to mimic neural signals from mechanoreceptors, and an
      extreme learning machine (ELM) chip to analyze spiking activity. Benefiting from
      intrinsic advantages of biologically inspired event-driven systems and massively
      parallel and energy-efficient processing capabilities of the ELM chip, the
      proposed architecture offers a fast and energy-efficient alternative for
      processing tactile information. Moreover, it provides the opportunity for the
      development of low-cost tactile modules for large-area applications by
      integration of sensors and processing circuits. We demonstrate the recognition
      capability of our system in a texture discrimination task, where it achieves a
      classification accuracy of 92% for categorization of ten graded textures. Our
      results confirm that there exists a tradeoff between response time and
      classification accuracy (and information transfer rate). A faster decision can be
      achieved at early time steps or by using a shorter time window. This, however,
      results in deterioration of the classification accuracy and information transfer
      rate. We further observe that there exists a tradeoff between the classification
      accuracy and the input spike rate (and thus energy consumption). Our work
      substantiates the importance of development of efficient sparse codes for
      encoding sensory data to improve the energy efficiency. These results have a
      significance for a wide range of wearable, robotic, prosthetic, and industrial
      applications.

PMID- 29570061
TI  - High-Voltage, Multiphasic, Nanosecond Pulses to Modulate Cellular Responses.
AB  - Nanosecond electric pulses are an effective power source in plasma medicine and
      biological stimulation, in which biophysical responses are governed by peak power
      and not energy. While uniphasic nanosecond pulse generators are widely available,
      the recent discovery that biological effects can be uniquely modulated by
      reversing the polarity of nanosecond duration pulses calls for the development of
      a multimodal pulse generator. This paper describes a method to generate
      nanosecond multiphasic pulses for biomedical use, and specifically demonstrates
      its ability to cancel or enhance cell swelling and blebbing. The generator
      consists of a series of the fundamental module, which includes a capacitor and a
      MOSFET switch. A positive or a negative phase pulse module can be produced based
      on how the switch is connected. Stacking the modules in series can increase the
      voltage up to 5 kV. Multiple stacks in parallel can create multiphase outputs. As
      each stack is independently controlled and charged, multiphasic pulses can be
      created to produce flexible and versatile pulse waveforms. The circuit topology
      can be used for high-frequency uniphasic or biphasic nanosecond burst pulse
      production, creating numerous opportunities for the generator in electroporation
      applications, tissue ablation, wound healing, and nonthermal plasma generation.

PMID- 29570060
TI  - A Real-Time Reconfigurable Multichip Architecture for Large-Scale Biophysically
      Accurate Neuron Simulation.
AB  - Simulation of brain neurons in real-time using biophysically meaningful models is
      a prerequisite for comprehensive understanding of how neurons process information
      and communicate with each other, in effect efficiently complementing in-vivo
      experiments. State-of-the-art neuron simulators are, however, capable of
      simulating at most few tens/hundreds of biophysically accurate neurons in real
      time due to the exponential growth in the interneuron communication costs with
      the number of simulated neurons. In this paper, we propose a real-time,
      reconfigurable, multichip system architecture based on localized communication,
      which effectively reduces the communication cost to a linear growth. All parts of
      the system are generated automatically, based on the neuron connectivity scheme.
      Experimental results indicate that the proposed system architecture allows the
      capacity of over 3000 to 19 200 (depending on the connectivity scheme)
      biophysically accurate neurons over multiple chips.

PMID- 29570062
TI  - Sub 100 nW Volatile Nano-Metal-Oxide Memristor as Synaptic-Like Encoder of
      Neuronal Spikes.
AB  - Advanced neural interfaces mediate a bioelectronic link between the nervous
      system and microelectronic devices, bearing great potential as innovative therapy
      for various diseases. Spikes from a large number of neurons are recorded leading
      to creation of big data that require online processing under most stringent
      conditions, such as minimal power dissipation and on-chip space occupancy. Here,
      we present a new concept where the inherent volatile properties of a nano-scale
      memristive device are used to detect and compress information on neural spikes as
      recorded by a multielectrode array. Simultaneously, and similarly to a biological
      synapse, information on spike amplitude and frequency is transduced in metastable
      resistive state transitions of the device, which is inherently capable of self
      resetting and of continuous encoding of spiking activity. Furthermore, operating
      the memristor in a very high resistive state range reduces its average in
      operando power dissipation to less than 100 nW, demonstrating the potential to
      build highly scalable, yet energy-efficient on-node processors for advanced
      neural interfaces.

PMID- 29570063
TI  - A Digitally Programmable Cytomorphic Chip for Simulation of Arbitrary Biochemical
      Reaction Networks.
AB  - Prior work has shown that compact analog circuits can faithfully represent and
      model fundamental biomolecular circuits via efficient log-domain cytomorphic
      transistor equivalents. Such circuits have emphasized basis functions that are
      dominant in genetic transcription and translation networks and deoxyribonucleic
      acid (DNA)-protein binding. Here, we report a system featuring digitally
      programmable 0.35 MUm BiCMOS analog cytomorphic chips that enable arbitrary
      biochemical reaction networks to be exactly represented thus enabling compact and
      easy composition of protein networks as well. Since all biomolecular networks can
      be represented as chemical reaction networks, our protein networks also include
      the former genetic network circuits as a special case. The cytomorphic analog
      protein circuits use one fundamental association-dissociation-degradation
      building-block circuit that can be configured digitally to exactly represent any
      zeroth-, first-, and second-order reaction including loading, dynamics,
      nonlinearity, and interactions with other building-block circuits. To address a
      divergence issue caused by random variations in chip fabrication processes, we
      propose a unique way of performing computation based on total variables and
      conservation laws, which we instantiate at both the circuit and network levels.
      Thus, scalable systems that operate with finite error over infinite time can be
      built. We show how the building-block circuits can be composed to form various
      network topologies, such as cascade, fan-out, fan-in, loop, dimerization, or
      arbitrary networks using total variables. We demonstrate results from a system
      that combines interacting cytomorphic chips to simulate a cancer pathway and a
      glycolysis pathway. Both simulations are consistent with conventional software
      simulations. Our highly parallel digitally programmable analog cytomorphic
      systems can lead to a useful design, analysis, and simulation tool for studying
      arbitrary large-scale biological networks in systems and synthetic biology.

PMID- 29570064
TI  - Fast and Precise Emulation of Stochastic Biochemical Reaction Networks With
      Amplified Thermal Noise in Silicon Chips.
AB  - The analysis and simulation of complex interacting biochemical reaction pathways
      in cells is important in all of systems biology and medicine. Yet, the dynamics
      of even a modest number of noisy or stochastic coupled biochemical reactions is
      extremely time consuming to simulate. In large part, this is because of the
      expensive cost of random number and Poisson process generation and the presence
      of stiff, coupled, nonlinear differential equations. Here, we demonstrate that we
      can amplify inherent thermal noise in chips to emulate randomness physically,
      thus alleviating these costs significantly. Concurrently, molecular flux in
      thermodynamic biochemical reactions maps to thermodynamic electronic current in a
      transistor such that stiff nonlinear biochemical differential equations are
      emulated exactly in compact, digitally programmable, highly parallel analog
      "cytomorphic" transistor circuits. For even small-scale systems involving just 80
      stochastic reactions, our 0.35-MUm BiCMOS chips yield a 311* speedup in the
      simulation time of Gillespie's stochastic algorithm over COPASI, a fast
      biochemical-reaction software simulator that is widely used in computational
      biology; they yield a 15 500* speedup over equivalent MATLAB stochastic
      simulations. The chip emulation results are consistent with these software
      simulations over a large range of signal-to-noise ratios. Most importantly, our
      physical emulation of Poisson chemical dynamics does not involve any inherently
      sequential processes and updates such that, unlike prior exact simulation
      approaches, they are parallelizable, asynchronous, and enable even more speedup
      for larger-size networks.

PMID- 29570065
TI  - A Scalable ISFET Sensing and Memory Array With Sensor Auto-Calibration for On
      Chip Real-Time DNA Detection.
AB  - This paper presents a novel CMOS-based system-on-chip with a 78 56 ion-sensitive
      field-effect transistor array using in-pixel quantization and compensation of
      sensor nonidealities. The pixel integrates sensing circuitry and memory cells to
      encode the ion concentration in time and store a calibration value per pixel.
      Temperature sensing pixels spread throughout the array allow temperature
      monitoring during the reaction. We describe the integration of the array as part
      of a lab-on-chip cartridge that plugs into a motherboard for power management,
      biasing, data acquisition, and temperature regulation. This forms a robust ion
      detection platform, which is demonstrated as a pH sensing system. We show that
      our calibration is able to perform readout with a linear spread of 0.3% and that
      the system exhibits a high pH sensitivity of 3.2 /pH. The complete system is
      shown to perform on-chip real-time DNA amplification and detection of lambda
      phage DNA by loop-mediated isothermal amplification.

PMID- 29570066
TI  - A High-Sensitivity Potentiometric 65-nm CMOS ISFET Sensor for Rapid E. coli
      Screening.
AB  - Foodborne bacteria, inducing outbreaks of infection or poisoning, have posed
      great threats to food safety. Potentiometric sensors can identify bacteria levels
      in food by measuring medium's pH changes. However, most of these sensors face the
      limitation of low sensitivity and high cost. In this paper, we developed a high
      sensitivity ion-sensitive field-effect transistor sensor. It is small sized, cost
      efficient, and can be massively fabricated in a standard 65-nm complementary
      metal-oxide-semiconductor process. A subthreshold pH-to-time-to-voltage
      conversion scheme was proposed to improve the sensitivity. Furthermore, design
      parameters, such as chemical sensing area, transistor size, and discharging time,
      were optimized to enhance the performance. The intrinsic sensitivity of
      passivation membrane was calculated as 33.2 mV/pH. It was amplified to 123.8
      mV/pH with a 0.01-pH resolution, which greatly exceeded 6.3 mV/pH observed in a
      traditional source-follower based readout structure. The sensing system was
      applied to Escherichia coli (E. coli) detection with densities ranging from 14 to
      140 cfu/mL. Compared to the conventional direct plate counting method (24 h),
      more efficient sixfold smaller screening time (4 h) was achieved to differentiate
      samples' E. coli levels. The demonstrated portable, time-saving, and low-cost
      prescreen system has great potential for food safety detection.

PMID- 29570067
TI  - Epoxy Chip-in-Carrier Integration and Screen-Printed Metalization for
      Multichannel Microfluidic Lab-on-CMOS Microsystems.
AB  - The integration of biosensors, microfluidics, and CMOS instrumentation provides a
      compact lab-on-CMOS microsystem well suited for high throughput measurement. This
      paper describes a new epoxy chip-in-carrier integration process and two planar
      metalization techniques for lab-on-CMOS that enable on-CMOS electrochemical
      measurement with multichannel microfluidics. Several design approaches with
      different fabrication steps and materials were experimentally analyzed to
      identify an ideal process that can achieve desired capability with high yield and
      low material and tool cost. On-chip electrochemical measurements of the
      integrated assembly were performed to verify the functionality of the chip-in
      carrier packaging and its capability for microfluidic integration. The newly
      developed CMOS-compatible epoxy chip-in-carrier process paves the way for full
      implementation of many lab-on-CMOS applications with CMOS ICs as core electronic
      instruments.

PMID- 29570069
TI  - A Two-Wired Ultra-High Input Impedance Active Electrode.
AB  - This paper presents a novel two-wired active electrode that achieves ultrahigh
      input impedance using power supply bootstrapping. The proposed circuit reduces
      the input capacitance of a buffer amplifier while enabling measurements using
      leads with only two wires, providing a low-complexity and low-cost solution for
      interference rejection and artifact reduction in dc-coupled dry-contact
      biopotential measurements. An implemented prototype shows that, even using
      standard operational amplifiers, an input capacitance as low as 71 fF can be
      obtained, maintaining a high impedance in a 0-1 kHz bandwidth, sufficient for
      ECG, EEG, and EMG measurements. The circuit has a simple and easily replicable
      implementation that requires no individual adjustment. A common mode rejection
      ratio (CMRR) above 103 dB at 50 Hz was achieved and the increased rejection to
      interference due to the potential divider effect was experimentally tested
      maintaining a 92-dB CMRR at 50 Hz with a 1.2-M source impedance unbalance. ECG
      measurements were conducted to validate the active electrode against a
      traditional alternative, and a test with dry-contact EEG electrodes was
      successfully conducted. Although the proposed circuit is intended to acquire
      superficial electrophysiological signals using dry electrodes, it can be used for
      measurement from other high-impedance sources, such as micropipette electrodes.

PMID- 29570068
TI  - Fully Automatic Three-Dimensional Ultrasound Imaging Based on Conventional B
      Scan.
AB  - Robotic ultrasound systems have turned into clinical use over the past few
      decades, increasing precision and quality of medical operations. In this paper,
      we propose a fully automatic scanning system for three-dimensional (3-D)
      ultrasound imaging. A depth camera was first used to obtain the depth data and
      color data of the tissue surface. Based on the depth image, the 3-D contour of
      the tissue was rendered and the scan path of ultrasound probe was automatically
      planned. Following the scan path, a 3-D translating device drove the probe to
      move on the tissue surface. Simultaneously, the B-scans and their positional
      information were recorded for subsequent volume reconstruction. In order to stop
      the scanning process when the pressure on the skin exceeded a preset threshold,
      two force sensors were attached to the front side of the probe for force
      measurement. In vitro and in vivo experiments were conducted for assessing the
      performance of the proposed system. Quantitative results show that the error of
      volume measurement was less than 1%, indicating that the system is capable of
      automatic ultrasound scanning and 3-D imaging. It is expected that the proposed
      system can be well used in clinical practices.

PMID- 29570070
TI  - A Unified Mathematical Model for Nano-Liposomal Drug Delivery to Solid Tumors.
AB  - Nanoparticles, such as liposomes, allow more targeted drug delivery for improved
      efficacy and/or reduced toxicity in both passive (e.g., Doxil) or active [e.g.,
      thermo-sensitive liposomes (TSL)] release forms compared with unencapsulated
      drugs (i.e., conventional chemotherapy). Optimization and evaluation of these
      different drug delivery systems are experimentally challenging because of varying
      tissue parameters as well as limited avaiability of experimental data. Here, we
      present a novel unified mathematical model that can simulate various liposomal
      drug delivery systems and unencapsulated drugs with a single set of equations. We
      use this model to evaluate the chemotherapy performance of free Doxorubicin (as
      drug), as well as various liposomal drug delivery systems: 1) passive liposomes
      (Doxil) and 2) active-triggered TSL with either intravascular (TSLi) or
      extravascular (TSLe)-triggered release. Furthermore, we implemented a more
      accurate expression to consider incomplete liposomal drug release. The proposed
      model matches experimental in vivo results in terms of maximum drug concentration
      in tumor. The simulations predict better overall performance for all liposomal
      delivery systems than free Dox. TSLe is shown to be more efficient for less
      permeable and perfused tumors than other systems. The optimal release rate is
      lower for TSLe and Doxil than TSLi. The performance of free DOX changes a little
      for varying tumor characteristics such as perfusion and permeability.

PMID- 29570071
TI  - Detection of Significant Copy Number Variations From Multiple Samples in Next
      Generation Sequencing Data.
AB  - Analyzing copy number variations (CNVs) from next-generation sequencing (NGS)
      data has become a common approach to detect disease susceptibility genes. The
      main challenge is how to utilize the NGS data with limited coverage depth to
      detect significant CNVs. Here, we introduce a new statistical method, the
      derivative of correlation coefficient (DCC), to detect significant CNVs that
      recurrently occur in multiple samples using read depth signals. We use a sliding
      window to calculate a correlation coefficient for each genome bin, and compute
      corresponding derivatives by fitting curves to the correlation coefficient. Then,
      the detection of significant CNVs was transformed into a problem of detecting
      significant derivatives reflecting genome breakpoints that can be solved using
      statistical hypothesis testing. We tested and compared the performance of DCC
      against several peer methods using a large number of simulation data sets, and
      validated DCC using several real sequencing data sets derived from the European
      Genome-Phenome archive, DNA Data Bank of Japan, and the 1000 Genomes Project.
      Experimental results suggest that DCC is an effective approach for identifying
      CNVs, outperforming peer methods in the terms of detection power and accuracy.
      DCC can be used to detect significant or recurrent CNVs in various NGS data sets,
      thus providing useful information to study genomic mutations and find disease
      susceptibility genes.

PMID- 29570072
TI  - Adaptive Detection and ISI Mitigation for Mobile Molecular Communication.
AB  - Current studies on modulation and detection schemes in molecular communication
      mainly focus on the scenarios with static transmitters and receivers. However,
      mobile molecular communication is needed in many envisioned applications, such as
      target tracking and drug delivery. Until now, investigations about mobile
      molecular communication have been limited. In this paper, a static transmitter
      and a mobile bacterium-based receiver performing random walk are considered. In
      this mobile scenario, the channel impulse response changes due to the dynamic
      change of the distance between the transmitter and the receiver. Detection
      schemes based on fixed distance fail in signal detection in such a scenario.
      Furthermore, the intersymbol interference (ISI) effect becomes more complex due
      to the dynamic character of the signal which makes the estimation and mitigation
      of the ISI even more difficult. In this paper, an adaptive ISI mitigation method
      and two adaptive detection schemes are proposed for this mobile scenario. In the
      proposed scheme, adaptive ISI mitigation, estimation of dynamic distance, and the
      corresponding impulse response reconstruction are performed in each symbol
      interval. Based on the dynamic channel impulse response in each interval, two
      adaptive detection schemes, concentration-based adaptive threshold detection and
      peak-time-based adaptive detection, are proposed for signal detection.
      Simulations demonstrate that the ISI effect is significantly reduced and the
      adaptive detection schemes are reliable and robust for mobile molecular
      communication.

PMID- 29570073
TI  - Computing Biomolecular System Steady-States.
AB  - A new approach to compute the equilibria and the steady-states of biomolecular
      systems modeled by bond graphs is presented. The approach is illustrated using a
      model of a biomolecular cycle representing a membrane transporter and a model of
      the mitochondrial electron transport chain.

PMID- 29570074
TI  - Maximum Likelihood Detection With Ligand Receptors for Diffusion-Based Molecular
      Communications in Internet of Bio-Nano Things.
AB  - Molecular Communication (MC) is a bio-inspired communication technique that uses
      molecules as a method of information transfer among nanoscale devices. MC
      receiver is an essential component having profound impact on the communication
      system performance. However, the interaction of the receiver with information
      bearing molecules has been usually oversimplified in modeling the reception
      process and developing signal detection techniques. In this paper, we focus on
      the signal detection problem of MC receivers employing receptor molecules to
      infer the transmitted messages encoded into the concentration of molecules, i.e.,
      ligands. Exploiting the observable characteristics of ligand-receptor binding
      reaction, we first introduce a Maximum Likelihood (ML) detection method based on
      instantaneous receptor occupation ratio, as aligned with the current MC
      literature. Then, we propose a novel ML detection technique, which exploits the
      amount of time the receptors stay unbound in an observation time window. A
      comprehensive analysis is carried out to compare the performance of the detectors
      in terms of bit error probability. In evaluating the detection performance,
      emphasis is given to the receptor saturation problem resulting from the
      accumulation of messenger molecules at the receiver as a consequence of
      intersymbol interference. The results reveal that detection based on receptor
      unbound time is quite reliable even in saturation, whereas the reliability of
      detection based on receptor occupation ratio substantially decreases as the
      receiver gets saturated. Finally, we also discuss the potential methods of
      implementing the detectors.

PMID- 29570075
TI  - Computational Prediction of HCV-Human Protein-Protein Interaction via Topological
      Analysis of HCV Infected PPI Modules.
AB  - In this paper, we have developed a framework for detection of protein-protein
      interactions (PPI) between Hepatitis-C virus (HCV) and human proteins based on
      PPI and gene ontology based information of the HCV infected proteins. First, a
      bipartite interaction network is formed between HCV proteins and human host
      proteins. Next, we have analyzed different topological properties of the
      interaction network and observed that degree of HCV-interacting proteins is
      significantly higher than non-interacting host proteins. We have also observed
      that the HCV interacted protein pairs are functionally similar with each other
      than the non-interacting pairs. Following the observations, we have applied an
      inference mechanism to predict novel interactions between HCV and human protein.
      The inference mechanism is based on partitioning the network formed by HCV
      interacted human proteins and their first neighbors in dense and functionally
      similar groups using a PPI network clustering algorithm. The groups are then
      analyzed to predict PPIs. The predicted interaction pairs are validated using
      literature search in PUBMED. Experimental evidence of over 50% of the predicted
      pairs are found in existing literatures by searching PUBMED. A Gene Ontology and
      pathway based analysis is also carried out to validate the identified modules
      biologically.

PMID- 29570076
TI  - Pinpoint Delivery of Molecules by Using Electron Beam Addressing Virtual Cathode
      Display.
AB  - Electroporation, a physical transfection method to introduce genomic molecules in
      selective living cells, could be implemented by microelectrode devices. A local
      electric field generated by a finer electrode can induces cytomembrane poration
      in the electrode vicinity. To employ fine, high-speed scanning electrodes, we
      developed a fine virtual cathode pattern, which was generated on a cell adhesive
      surface of 100-nm-thick SiN membrane by inverted-electron beam lithography. The
      SiN membrane works as both a vacuum barrier and the display screen of the virtual
      cathode. The kinetic energy of the incident primary electrons to the SiN membrane
      was completely blocked, whereas negative charges and leaking electric current
      appeared on the surface of the dielectric SiN membrane within a region of 100 nm.
      Locally controlled transmembrane molecular delivery was demonstrated on adhered
      C2C12 myoblast cells in a culturing medium with fluorescent dye propidium iodide
      (PI). Increasing fluorescence of pre-diluted PI indicated local poration and
      transmembrane inflow at the virtual cathode position, as well as intracellular
      diffusion. The transmembrane inflows depended on beam duration time and
      acceleration voltage. At the post-molecular delivery, a slight decrease in
      intracellular PI fluorescence intensity indicates membrane recovery from the
      poration. Cell viability was confirmed by time-lapse cell imaging of post
      exposure cell migration.

PMID- 29570077
TI  - Biophysical Characteristics of Human Neuroblastoma Cell in Oligomeric $?beta $ 
      Amyloid (1-40) Cytotoxicity.
AB  - Beta amyloid ( ) peptide, which is a common neuropathological hallmark deposit in
      the brain of patients with Alzheimer's disease, typically comprises 39-43 amino
      acid residues. peptides exist as isoforms of and with various lengths. In this
      research, atomic force microscopy (AFM) was applied to investigate aggregations
      in Hank's Balanced Salt Solution. Toxic effect of oligomer was investigated in
      live SH-SY5Y neuroblastoma cells by characterizing cell morphology and cell
      mechanics using high-resolution AFM scanning. oligomer-induced cytoskeleton
      reorganization was also observed under confocal microscopy, and it can account
      for reduction in Young's modulus of cells. Meanwhile, phosphorylation of tau
      increased after oligomer treatment, possibly resulting in microtubule
      disassembly. This paper demonstrates the linkage between cellular mechanical
      changes and neurodegeneration mediated by . The method used implies promising
      applications of real-time monitoring of cellular mechanical properties given the
      toxic effects of on living neuronal cells.

PMID- 29570078
TI  - Axonal Channel Capacity in Neuro-Spike Communication.
AB  - Novel nano-scale communication techniques are inspired by biological systems.
      Neuro-spike communication is an example of this communication paradigm which
      transfers vital information about external and internal conditions of the body
      through the nervous system. The analysis of this communication paradigm is
      beneficial to exploit in the artificial neural systems where nano-machines are
      linked to neurons to treat the neurodegenerative diseases. In these networks,
      nano-machines are used to replace the damaged segments of the nervous system and
      they exactly behave like biological entities. In neuro-spike communication,
      neurons / nano-machines exploit the electro-chemical spikes and molecular
      communication to transfer information. This communication paradigm can be divided
      into three main parts, namely the axonal pathway, the synaptic transmission, and
      the spike generation. In this paper, we focus on the axonal transmission part as
      a separate channel since the capacity of the axonal pathway has a significant
      effect on the capacity of neuro-spike communication channel. In thinner axons,
      the capacity of this part is the bottleneck of the neuro-spike communication
      channel capacity. Hence, we investigate the restricting factors of the axonal
      transmission which limit its capacity. We derive the capacity of single-input
      single-output and multiple-input single-output (MISO) axonal channels. In the
      MISO case, we investigate the effect of the correlation among inputs on the
      channel capacity. Moreover, we derive a closed form description for the optimum
      value of the input spike rate to maximize the capacity of the axonal channel when
      the information is encoded by firing rate of neurons / nano-machines.

PMID- 29570079
TI  - Shannon Meets Fick on the Microfluidic Channel: Diffusion Limit to Sum Broadcast
      Capacity for Molecular Communication.
AB  - Molecular communication (MC) over a microfluidic channel with flow is
      investigated based on Shannon's channel capacity theorem and Fick's laws of
      diffusion. Specifically, the sum capacity for MC between a single transmitter and
      multiple receivers (broadcast MC) is studied. The transmitter communicates by
      using different types of signaling molecules with each receiver over the
      microfluidic channel. The transmitted molecules propagate through microfluidic
      channel until reaching the corresponding receiver. Although the use of different
      types of molecules provides orthogonal signaling, the sum broadcast capacity may
      not scale with the number of the receivers due to physics of the propagation
      (interplay between convection and diffusion based on distance). In this paper,
      the performance of broadcast MC on a microfluidic chip is characterized by
      studying the physical geometry of the microfluidic channel and leveraging the
      information theory. The convergence of the sum capacity for microfluidic
      broadcast channel is analytically investigated based on the physical system
      parameters with respect to the increasing number of molecular receivers. The
      analysis presented here can be useful to predict the achievable information rate
      in microfluidic interconnects for the biochemical computation and microfluidic
      multi-sample assays.

PMID- 29570080
TI  - Erratum to "Nanocommunication via FRET With DyLight Dyes Using Multiple Donors
      and Acceptors".
AB  - In the above paper [1], an exponent is missing from equations (5) and (6). The
      correct version of the equations are as follows.

PMID- 29570081
TI  - Robust Visual Tracking Revisited: From Correlation Filter to Template Matching.
AB  - In this paper, we propose a novel matching based tracker by investigating the
      relationship between template matching and the recent popular correlation filter
      based trackers (CFTs). Compared to the correlation operation in CFTs, a
      sophisticated similarity metric termed mutual buddies similarity is proposed to
      exploit the relationship of multiple reciprocal nearest neighbors for target
      matching. By doing so, our tracker obtains powerful discriminative ability on
      distinguishing target and background as demonstrated by both empirical and
      theoretical analyses. Besides, instead of utilizing single template with the
      improper updating scheme in CFTs, we design a novel online template updating
      strategy named memory, which aims to select a certain amount of representative
      and reliable tracking results in history to construct the current stable and
      expressive template set. This scheme is beneficial for the proposed tracker to
      comprehensively understand the target appearance variations, recall some stable
      results. Both qualitative and quantitative evaluations on two benchmarks suggest
      that the proposed tracking method performs favorably against some recently
      developed CFTs and other competitive trackers.

PMID- 29570082
TI  - An Analytic Gabor Feedforward Network for Single-Sample and Pose-Invariant Face
      Recognition.
AB  - Gabor magnitude is known to be among the most discriminative representations for
      face images due to its space- frequency co-localization property. However, such
      property causes adverse effects even when the images are acquired under moderate
      head pose variations. To address this pose sensitivity issue and other moderate
      imaging variations, we propose an analytic Gabor feedforward network which can
      absorb such moderate changes. Essentially, the network works directly on the raw
      face images and produces directionally projected Gabor magnitude features at the
      hidden layer. Subsequently, several sets of magnitude features obtained from
      various orientations and scales are fused at the output layer for final
      classification decision. The network model is analytically trained using a single
      sample per identity. The obtained solution is globally optimal with respect to
      the classification total error rate. Our empirical experiments conducted on five
      face data sets (six subsets) from the public domain show encouraging results in
      terms of identification accuracy and computational efficiency.

PMID- 29570083
TI  - Camera-Aware Multi-Resolution Analysis for Raw Image Sensor Data Compression.
AB  - We propose novel lossless and lossy compression schemes for color filter array
      (CFA) sampled images based on the Camera-A ware Multi-Resolution Analysis, or
      CAMRA. Specifically, by CAMRA we refer to modifications that we make to wavelet
      transform of CFA sampled images in order to achieve a very high degree of
      decorrelation at the finest scale wavelet coefficients; and a series of color
      processing steps applied to the coarse scale wavelet coefficients, aimed at
      limiting the propagation of lossy compression errors through the subsequent
      camera processing pipeline. We validated our theoretical analysis and the
      performance of the proposed compression schemes using the images of natural
      scenes captured in a raw format. The experimental results verify that our
      proposed methods improve coding efficiency relative to the standard and the state
      of-the-art compression schemes for CFA sampled images.

PMID- 29570084
TI  - Unsupervised Uncertainty Estimation Using Spatiotemporal Cues in Video Saliency
      Detection.
AB  - In this paper, we address the problem of quantifying the reliability of
      computational saliency for videos, which can be used to improve saliency-based
      video processing algorithms and enable more reliable performance and objective
      risk assessment of saliency-based video processing applications. Our approach to
      quantify such reliability is twofold. First, we explore spatial correlations in
      both the saliency map and the eye-fixation map. Then, we learn the spatiotemporal
      correlations that define a reliable saliency map. We first study spatiotemporal
      eye-fixation data from the public CRCNS data set and investigate a common feature
      in human visual attention, which dictates a correlation in saliency between a
      pixel and its direct neighbors. Based on the study, we then develop an algorithm
      that estimates a pixel-wise uncertainty map that reflects our supposed confidence
      in the associated computational saliency map by relating a pixel's saliency to
      the saliency of its direct neighbors. To estimate such uncertainties, we measure
      the divergence of a pixel, in a saliency map, from its local neighborhood. In
      addition, we propose a systematic procedure to evaluate uncertainty estimation
      performance by explicitly computing uncertainty ground truth as a function of a
      given saliency map and eye fixations of human subjects. In our experiments, we
      explore multiple definitions of locality and neighborhoods in spatiotemporal
      video signals. In addition, we examine the relationship between the parameters of
      our proposed algorithm and the content of the videos. The proposed algorithm is
      unsupervised, making it more suitable for generalization to most natural videos.
      Also, it is computationally efficient and flexible for customization to specific
      video content. Experiments using three publicly available video data sets show
      that the proposed algorithm outperforms state-of-the-art uncertainty estimation
      methods with improvement in accuracy up to 63% and offers efficiency and
      flexibility that make it more useful in practical situations.

PMID- 29570085
TI  - Structure-Revealing Low-Light Image Enhancement Via Robust Retinex Model.
AB  - Low-light image enhancement methods based on classic Retinex model attempt to
      manipulate the estimated illumination and to project it back to the corresponding
      reflectance. However, the model does not consider the noise, which inevitably
      exists in images captured in low-light conditions. In this paper, we propose the
      robust Retinex model, which additionally considers a noise map compared with the
      conventional Retinex model, to improve the performance of enhancing low-light
      images accompanied by intensive noise. Based on the robust Retinex model, we
      present an optimization function that includes novel regularization terms for the
      illumination and reflectance. Specifically, we use norm to constrain the piece
      wise smoothness of the illumination, adopt a fidelity term for gradients of the
      reflectance to reveal the structure details in low-light images, and make the
      first attempt to estimate a noise map out of the robust Retinex model. To
      effectively solve the optimization problem, we provide an augmented Lagrange
      multiplier based alternating direction minimization algorithm without logarithmic
      transformation. Experimental results demonstrate the effectiveness of the
      proposed method in low-light image enhancement. In addition, the proposed method
      can be generalized to handle a series of similar problems, such as the image
      enhancement for underwater or remote sensing and in hazy or dusty conditions.

PMID- 29570086
TI  - Learning Clip Representations for Skeleton-Based 3D Action Recognition.
AB  - This paper presents a new representation of skeleton sequences for 3D action
      recognition. Existing methods based on hand-crafted features or recurrent neural
      networks cannot adequately capture the complex spatial structures and the long
      term temporal dynamics of the skeleton sequences, which are very important to
      recognize the actions. In this paper, we propose to transform each channel of the
      3D coordinates of a skeleton sequence into a clip. Each frame of the generated
      clip represents the temporal information of the entire skeleton sequence and one
      particular spatial relationship between the skeleton joints. The entire clip
      incorporates multiple frames with different spatial relationships, which provide
      useful spatial structural information of the human skeleton. We also propose a
      multitask convolutional neural network (MTCNN) to learn the generated clips for
      action recognition. The proposed MTCNN processes all the frames of the generated
      clips in parallel to explore the spatial and temporal information of the skeleton
      sequences. The proposed method has been extensively tested on six challenging
      benchmark datasets. Experimental results consistently demonstrate the superiority
      of the proposed clip representation and the feature learning method for 3D action
      recognition compared to the existing techniques.

PMID- 29570087
TI  - Generalization of the Dark Channel Prior for Single Image Restoration.
AB  - Images degraded by light scattering and absorption, such as hazy, sandstorm, and
      underwater images, often suffer color distortion and low contrast because of
      light traveling through turbid media. In order to enhance and restore such
      images, we first estimate ambient light using the depth-dependent color change.
      Then, via calculating the difference between the observed intensity and the
      ambient light, which we call the scene ambient light differential, scene
      transmission can be estimated. Additionally, adaptive color correction is
      incorporated into the image formation model (IFM) for removing color casts while
      restoring contrast. Experimental results on various degraded images demonstrate
      the new method outperforms other IFM-based methods subjectively and objectively.
      Our approach can be interpreted as a generalization of the common dark channel
      prior (DCP) approach to image restoration, and our method reduces to several DCP
      variants for different special cases of ambient lighting and turbid medium
      conditions.

PMID- 29570088
TI  - Deep Action Parsing in Videos With Large-Scale Synthesized Data.
AB  - Action parsing in videos with complex scenes is an interesting but challenging
      task in computer vision. In this paper, we propose a generic 3D convolutional
      neural network in a multi-task learning manner for effective Deep Action Parsing
      (DAP3D-Net) in videos. Particularly, in the training phase, action localization,
      classification, and attributes learning can be jointly optimized on our
      appearance-motion data via DAP3D-Net. For an upcoming test video, we can describe
      each individual action in the video simultaneously as: Where the action occurs,
      What the action is, and How the action is performed. To well demonstrate the
      effectiveness of the proposed DAP3D-Net, we also contribute a new Numerous
      category Aligned Synthetic Action data set, i.e., NASA, which consists of 200 000
      action clips of over 300 categories and with 33 pre-defined action attributes in
      two hierarchical levels (i.e., low-level attributes of basic body part movements
      and high-level attributes related to action motion). We learn DAP3D-Net using the
      NASA data set and then evaluate it on our collected Human Action Understanding
      data set and the public THUMOS data set. Experimental results show that our
      approach can accurately localize, categorize, and describe multiple actions in
      realistic videos.

PMID- 29570089
TI  - Content-Adaptive Superpixel Segmentation.
AB  - Superpixel segmentation targets at grouping pixels in an image into atomic
      regions whose boundaries align well with the natural object boundaries. This
      paper first proposes a new feature representation for superpixel segmentation
      that holistically embraces color, contour, texture, and spatial features. Then,
      we introduce a clustering-based discriminability measure to iteratively evaluate
      the importance of different features. Integrating the feature representation and
      the discriminability measure, we propose a novel content-adaptive superpixel
      (CAS) segmentation algorithm. CAS is able to automatically and iteratively adjust
      the weights of different features to fit various properties of image instances.
      Experiments on several challenging datasets demonstrate that the proposed CAS
      outperforms the state-of-the-art methods and has a low computational cost.

PMID- 29570090
TI  - Shaping up synthetic cells.
AB  - How do the cells in our body reconfigure their shape to achieve complex tasks
      like migration and mitosis, yet maintain their shape in response to forces
      exerted by, for instance, blood flow and muscle action? Cell shape control is
      defined by a delicate mechanical balance between active force generation and
      passive material properties of the plasma membrane and the cytoskeleton. The
      cytoskeleton forms a space-spanning fibrous network comprising three subsystems:
      actin, microtubules and intermediate filaments. Bottom-up reconstitution of
      minimal synthetic cells where these cytoskeletal subsystems are encapsulated
      inside a lipid vesicle provides a powerful avenue to dissect the force balance
      that governs cell shape control. Although encapsulation is technically demanding,
      a steady stream of advances in this technique has made the reconstitution of
      shape-changing minimal cells increasingly feasible. In this topical review we
      provide a route-map of the recent advances in cytoskeletal encapsulation
      techniques and outline recent reports that demonstrate shape change phenomena in
      simple biomimetic vesicle systems. We end with an outlook toward the next steps
      required to achieve more complex shape changes with the ultimate aim of building
      a fully functional synthetic cell with the capability to autonomously grow,
      divide and move.

PMID- 29570091
TI  - Experimental validation of predicted cancer genes using FRET.
AB  - Huge amounts of data are generated in genome wide experiments, designed to
      investigate diseases with complex genetic causes. Follow up of all potential
      leads produced by such experiments is currently cost prohibitive and time
      consuming. Gene prioritization tools alleviate these constraints by directing
      further experimental efforts towards the most promising candidate targets.
      Recently a gene prioritization tool called MaxLink was shown to outperform other
      widely used state-of-the-art prioritization tools in a large scale in silico
      benchmark. An experimental validation of predictions made by MaxLink has however
      been lacking. In this study we used Fluorescence Resonance Energy Transfer, an
      established experimental technique for detection of protein-protein interactions,
      to validate potential cancer genes predicted by MaxLink. Our results provide
      confidence in the use of MaxLink for selection of new targets in the battle with
      polygenic diseases.

PMID- 29570092
TI  - Facile preparation of surfactant-free Au NPs/RGO/Ni foam for degradation of 4
      nitrophenol and detection of hydrogen peroxide.
AB  - The application of Au nanoparticles (Au NPs) often requires surface modification
      with chemical surfactants, which dramatically reduce the surface activity and
      increase the chemical contamination and cost of Au NPs. In this research, we have
      developed a novel Au NPs/reduced graphene oxide/Ni foam hybrid (Au NPs/RGO/NiF)
      by in situ reduction through ascorbic acid and replacement reaction. This method
      is green, facile and efficient. The Au NPs are free of chemical surfactants and
      are homogeneously distributed on the surface of the RGO/NiF. The as-prepared Au
      NPs/RGO/NiF hybrid is uniform, stable and exhibits not only a high reduction
      efficiency for the reduction of 4-nitrophenol with a catalytic kinetic constant
      of up to 0.46 min-1 (0.15 cm3 catalysis) but also a sensitive and selective
      detection of H2O2 with a detection limit of ~1.60 MUM.

PMID- 29570094
TI  - Dendrimer ligands-capped CH3NH3PbBr3 perovskite nanocrystals with delayed halide
      exchange and record stability against both moisture and water.
AB  - CH3NH3PbBr3 perovskite nanocrystals (NCs) suffer from poor stability because of
      their high sensitivity to environmental moisture and water. To solve this
      problem, previous works mainly focus on embedding perovskite NCs into water
      resistant matrix to form large composites (size of microns or larger). As an
      alternative solution without serious changing of NC size, enhancing the stability
      of perovskite NCs themselves by ligand engineering is rarely reported. In this
      work, we used hyperbranched polyamidoamine (PAMAM) dendrimers with two different
      generations (G0 and G4) to synthesize CH3NH3PbBr3 perovskite NCs with high
      photoluminescence (PL) quantum yields (QY) above 70% and a new record stability.
      A novel dendrimers generation-dependent stability of perovskite NCs was observed.
      The water-resistance time is 18 h (27 h) for perovskite NCs capped by G0 (G4)
      generation of PAMAM, which is 7 times (11 times) longer than that of traditional
      oleic acid-capped NCs. Similar PAMAM generation-related stability is also
      observed in moisture-resistance tests. The stability time against moisture is 500
      h (800 h) for G0 (G4) generation of PAMAM-capped perovskite NCs, which is a new
      record stability time against moisture for CH3NH3PbBr3 perovskite NCs. In
      addition, our results also indicate that PAMAM ligands outside perovskite NCs can
      dramatically slow down the speed of halide exchange. Even for the mixture of
      perovskite NCs with two different halide composition, the original luminescence
      properties of PAMAM-capped perovskite NCs can retain after mixing. In view of
      slow halide exchange speed, excellent water and moisture stability, PAMAM
      dendrimers-capped perovskite NCs and their mixture are available as color
      conversion single layer in fabrication of light-emitting diodes (LED).

PMID- 29570093
TI  - Synthesis of highly stable cyanine-dye-doped silica nanoparticle for biological
      applications.
AB  - Cyanine dyes are widely used in biological labeling and imaging because of their
      narrow near infrared emission, good brightness and high flexibility in
      functionalization, which not only enables multiplex analysis and multi-color
      imaging, but also greatly reduces autofluorescence from biological matter and
      increases signal-to-noise ratio. Unfortunately, their poor chemical- and photo
      stability strongly limits their applications. The incorporation of cyanine dyes
      in silica nanoparticles provides a solution to the problem. On one hand, the
      incorporation of cyanine dyes in silica matrix can enhance their chemical- and
      photo-stability and increase brightness of the nanomaterials. On the other hand,
      silica matrix provides an optimized condition to host the dye, which helps to
      maintain their fluorescent properties during application. In addition, the well
      established silane technique provides numerous functionalities for diverse
      applications. However, commercially available cyanine dyes are not very stable at
      high alkaline conditions, which will gradually lose their fluorescence over time.
      Our results showed that cyanine dyes are very vulnerable in the reverse micelle
      system, in which they will lose their fluorescence in less than half an hour. The
      existence of surfactant could greatly promote degradation of cyanine dyes.
      Fluorescent silica nanoparticles cannot be obtained at the high alkaline
      condition with the existence of surfactant. In contrast, the cyanine dyes are
      relatively stable in Stober media. Owing to the fast formation of silica
      particles in Stober media, the exposure time of cyanine dye in alkaline solution
      was greatly reduced, and highly fluorescent particles with good morphology and
      size distribution could be obtained via Stober approach. However, the increasing
      water content in the Stober could reduce the stability of cyanine dyes, which
      should be avoided. This research here provides a clear guidance on how to
      successfully synthesize cyanine dye-doped silica nanoparticles with good
      morphology, size distribution, stability and brightness.

PMID- 29570095
TI  - Doped bottom-contact organic field-effect transistors.
AB  - The influence of doping on doped bottom-gate bottom-contact organic field-effect
      transistors (OFETs) is discussed. It is shown that the inclusion of a doped layer
      at the dielectric/organic semiconductor layer leads to a significant reduction in
      the contact resistances and a fine control of the threshold voltage. Through
      varying the thickness of the doped layer, a linear shift of threshold voltage V T
      from -3.1 to -0.22 V is observed for increasing thickness of doped layer.
      Meanwhile, the contact resistance at the source and drain electrode is reduced
      from 138.8 MOmega at V GS = -10 V for 3 nm to 0.3 MOmega for 7 nm thick doped
      layers. Furthermore, an increase of charge mobility is observed for increasing
      thickness of doped layer. Overall, it is shown that doping can minimize injection
      barriers in bottom-contact OFETs with channel lengths in the micro-meter regime,
      which has the potential to increase the performance of this technology further.

PMID- 29570096
TI  - Smart self-tightening surgical suture from a tough bio-based hyperbranched
      polyurethane/reduced carbon dot nanocomposite.
AB  - Design and fabrication of a smart bio-based polymeric material with potent
      biocompatibility and high performance still remain a challenge in the biomedical
      realm. In this context, a potential smart suture was fabricated from starch
      modified hyperbranched polyurethane (HPU) nanocomposites with different weight
      percentages of reduced carbon dots for the first time. The desired mechanical
      (tensile strength: 32.14 MPa, elongation at break: 1576% and toughness 439.28 MJ
      m-3) and thermal (286  degrees C) attributes of the suture were achieved with 2
      wt% of reduced carbon dots in an HPU matrix. The non-contact self-tightening
      behavior was observed just within 15 s at body temperature of 37  degrees C +/- 1
      degrees C with notable shape fixity (99.6%) and shape recovery (99.7%) effects.
      The nanocomposites displayed in vitro biodegradability and hemocompatibility. Low
      lactate dehydrogenase activity and minimal red blood cell lysis indicated the
      anti-thrombogenicity and anti-hemolytic properties of the nanocomposites. The
      suitability of the fabricated nanocomposites as a smart biomaterial was supported
      by the inherent biocompatibility as observed by the growth and proliferation of
      smooth muscle cells and endothelial cells. Furthermore, they exhibited minimal
      immunogenic response (TNF alpha release). Thus, the study paves the way to
      biodegradable HPU nanocomposites as advanced non-contact triggered rapid self
      tightening surgical sutures for biomedical applications.

PMID- 29570097
TI  - Cytotoxicity of titanium carbonitride coatings for prostodontic alloys with
      different amounts of carbon and nitrogen.
AB  - The aim of our work was to examine the cytotoxicity of NiCr alloys coated with
      Ti(C,N) with different amounts of C and N in the layer on human gingival
      fibroblasts. Cells were cultured for 24 hours in the alloy extracts or on the
      surface of tested materials. The viability of the cells exposed to 1-, 3-, 5- and
      7-day extracts did not change in comparison to the viability of cells cultured in
      a control medium assayed by an MTT test. Moreover, the flow cytometry analysis of
      fibroblasts cultured in direct contact with tested alloys revealed that all
      coatings except TiC did not induce apoptosis or necrosis. Interestingly, 24 hour
      fibroblast culture on alloys with Ti(C,N) coatings showed that the number of
      fibroblasts adhered to these alloys, evaluated by scanning electron microscope,
      increased with an increase in the content of nitrogen in the layer. The present
      study demonstrates that Ti(C,N) coatings were not cytotoxic and did not induce
      apoptosis in Ti(C,N) extracts, nor in direct contact with gingival fibroblasts,
      and can be considered for biomedical applications in the future.

PMID- 29570098
TI  - Exocytosis of gold nanoparticle and photosensitizer from cancer cells and their
      effects on photodynamic and photothermal processes.
AB  - We first illustrate the faster decrease of the photothermal (PT) effect with the
      delay time of laser treatment, in which the illumination of a 1064 nm laser
      effectively excites the localized surface plasmon (LSP) resonance of cell-up
      taken gold nanoring (NRI) linked with a photosensitizer (PS), when compared with
      the photodynamic (PD) effect produced by the illumination of a 660 nm laser for
      effective PS excitation. The measurement results of the metal contents of Au NRI
      and PS based on inductively coupled plasma mass spectroscopy and the PS
      fluorescence intensity based on flow cytometry show that the linkage of NRI and
      PS is rapidly broken for releasing PS through the effect of glutathione in
      lysosome after cell uptake. Meanwhile, NRI escapes from a cell with a high rate
      such that the PT effect decays fast while the released PS can stay inside a cell
      longer for producing a prolonged PD effect. The effective delivery of PS through
      the linkage with Au NRI for cell uptake and the advantageous effect of LSP
      resonance at a PS absorption wavelength on the PD process are also demonstrated.

PMID- 29570099
TI  - Comment on 'temperature dependent spectroscopic and excited state dynamics of 3
      hydroxychromones with electron donor and acceptor substituents'.

PMID- 29570100
TI  - Inhibition of anaplastic lymphoma kinase promotes apoptosis and suppresses
      proliferation in human hepatocellular carcinoma.
AB  - Our study was to examine the roles of crizotinib and ceritinib in hepatocellular
      carcinoma (HCC) cells and explore the possible mechanisms. MTT assay was employed
      to examine the proliferation of five HCC cell lines treated with various
      concentrations of crizotinib or ceritinib. HepG2 and HCCLM3 cells were incubated
      with 2 nmol/l ceritinib for 1 week, followed by crystal violet staining and cell
      counting. Protein amounts of t-ALK, p-ALK, t-AKT, p-AKT, t-ERK, p-ERK, Mcl-1,
      survivin, and XIAP in HepG2 cells under different culture conditions were
      evaluated by western blot. HepG2 and HCCLM3 cells were treated with vehicle or
      ceritinib and measured by flow cytometry apoptosis analysis with Annexin
      V/propidium iodide staining. MTT assay showed that both crizotinib and ceritinib
      suppressed the proliferation of various human HCC cells. Crystal violet staining
      analysis also indicated that ceritinib effectively inhibited human HCC cell
      proliferation. Western blot analysis indicated that both crizotinib and ceritinib
      inhibited ALK, AKT, and ERK phosphorylations. In addition, ceritinib reduced
      antiapoptotic gene expressions in HepG2 cells. Flow cytometry analysis indicated
      that ceritinib induced HepG2 and HCCLM3 cells apoptosis. ALK inhibitor exhibited
      antitumor effects by inhibiting ALK activation, repressing AKT and ERK pathways,
      and suppressing antiapoptotic gene expressions, which subsequently promoted
      apoptosis and suppressed HCC cell proliferations.

PMID- 29570101
TI  - Venous thromboembolic events in patients with lung cancer treated with cisplatin
      based versus carboplatin/nedaplatin-based chemotherapy.
AB  - An association between chemotherapy and venous thromboembolic events (VTEs) in
      patients with cancer is well established, with cisplatin (CDDP) being one of the
      most well-studied risk factors. However, whether CDDP is more strongly associated
      with occurrence of VTEs than carboplatin (CBDCA) or nedaplatin (CDGP) is
      controversial. Our purposes were to characterize patients with lung cancer and in
      hospital VTEs, identify risk factors associated with VTEs, and compare the risks
      associated with CDDP-based versus CBDCA/CDGP-based chemotherapy. We
      retrospectively identified patients with lung cancer who underwent platinum-based
      chemotherapy from April 2012 to March 2015 from a national inpatient database in
      Japan. We used multivariable logistic regression analysis to analyze associations
      between various factors, including chemotherapy regimens and VTE. Of 235 104
      eligible patients, 675 (0.29%) had VTEs after receiving platinum-based
      chemotherapy while hospitalized. Multivariable analysis showed that age, activity
      of daily living index, and invasive medical procedures were significant risk
      factors for the occurrence of VTE. Furthermore, CDDP-based chemotherapy was
      associated with a higher rate of VTE than CBDCA/CDGP-based chemotherapy (adjusted
      odds ratio: 1.35; 95% confidence interval: 1.08-1.68; P<0.01). In conclusion,
      CDDP-based chemotherapy is a stronger risk factor for VTEs than CBDCA/CDGP-based
      chemotherapy in patients with lung cancer.

PMID- 29570102
TI  - Evidence for Somatic Hypersensitivity in Veterans With Gulf War Illness and
      Gastrointestinal Symptoms.
AB  - INTRODUCTION: Over 25% of Persian Gulf War (PGW) veterans with Gulf War Illness
      (GWI) (chronic health symptoms of undetermined etiology) developed
      gastrointestinal (GI) (diarrhea and abdominal pain) and other somatic symptoms.
      OBJECTIVES: Our study objective was to determine if veterans with GWI and GI
      symptoms exhibit heightened patterns of somatic pain perception
      (hypersensitivity) across nociceptive stimuli modalities. METHODS: Participants
      were previously deployed GW Veterans with GWI and GI symptoms (n=53); veterans
      with GWI without GI symptom (n=47); and veteran controls (n=38). We determined
      pain thresholds for contact thermal, cold pressor, and ischemic stimuli. RESULTS:
      Veterans with GWI and GI symptoms showed lower pain thresholds (P<0.001) for each
      stimulus. There was also overlap of somatic hypersensitivities among veterans
      with GI symptoms with 20% having hypersensitivity to all 3 somatic stimuli.
      Veterans with GWI and GI symptoms also showed a significant correlation between
      mechanical visual analog scale abdominal pain ratings and heat pain threshold,
      cold pressor threshold, and ischemic pain threshold/tolerance. DISCUSSION: Our
      findings show that there is widespread somatic hypersensitivity in veterans with
      GWI/GI symptoms that is positively correlated with abdominal pain ratings. In
      addition, veterans with somatic hypersensitivity that overlap have the greatest
      number of extraintestinal symptoms. These findings may have a translational
      benefit: strategies for developing more effective therapeutic agents that can
      reduce and/or prevent somatic and GI symptoms in veterans deployed to future
      military conflicts.

PMID- 29570103
TI  - Invitation strategies and coverage in the population-based cancer screening
      programmes in the European Union.
AB  - The aim of this study was to describe the compliance of the population-based
      cancer screening programmes in the European Union Member States to the invitation
      strategies enumerated in the European Guidelines and the impact of such
      strategies on the invitational coverage. Experts in screening programme
      monitoring from the respective countries provided data. Coverage by invitation
      was calculated as the proportion of individuals in the target age range receiving
      a screening invitation over the total number of annualized eligible population.
      The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national
      or regional population-based screening programmes are described. Individual mail
      invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening
      programmes. Faecal occult blood test kits are sent by post in 17 of the
      colorectal cancer screening programmes. The majority of programmes claimed to
      have a population registry, although some use health insurance data as the
      database for sending invitations. At least 95% invitation coverage was reached by
      16 breast, six cervical and five colorectal screening programmes. Majority of the
      programmes comply with the invitation strategies enumerated in the European
      guidelines, although there is still scope for improvements. Coverage by
      invitation is below the desirable level in many population-based cancer screening
      programmes in European Union.

PMID- 29570104
TI  - Serum uric acid and cancer mortality and incidence: a systematic review and meta
      analysis.
AB  - Elevated serum uric acid (SUA) is a marker of chronic inflammation and has been
      suggested to be associated with increased risk of cancer, but its antioxidant
      capacity would justify an anticancer effect. Previous meta-analyses did not
      include all available results. We conducted a systematic review of prospective
      studies on SUA level and risk of all cancers and specific cancers, a conducted a
      meta-analysis based on random-effects models for high versus low SUA level as
      well as for an increase in 1 mg/dl SUA. The relative risk of all cancers for high
      versus low SUA level was 1.11 (95% confidence interval: 0.94-1.27; 11 risk
      estimates); that for a mg/dl increase in SUA level was 1.03 (95% confidence
      interval: 0.99-1.07). Similar results were obtained for lung cancer (six risk
      estimates) and colon cancer (four risk estimates). Results for other cancers were
      sparse. Elevated SUA levels appear to be associated with a modest increase in
      overall cancer risk, although the combined risk estimate did not reach the formal
      level of statistical significance. Results for specific cancers were limited and
      mainly negative.

PMID- 29570105
TI  - Folate intake, serum folate, and risk of esophageal cancer: a systematic review
      and dose-response meta-analysis.
AB  - The dose-response relationship between folate and the risk of esophageal cancer
      (EC) is not clear. To further elucidate their relationships, we carried out a
      dose-response meta-analysis of folate intake, serum folate, and the risk of EC.
      PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were
      searched for observational studies until September 2016. Then, we carried out a
      systematic review and dose-response meta-analysis using Stata 14.0 software.
      Subgroup analyses were further carried out according to study characteristics and
      adjustment confounders. A total of 23 studies with a total of 3886 patients were
      enrolled in this study. The pooled odds ratios for EC in the highest versus the
      lowest levels of folate intake and serum folate were 0.64 (0.54-0.76, P<0.001)
      and 0.45 (0.19-1.07, P=0.071), respectively. Dose-response meta-analyses were
      carried out to assess associations between folate intake, serum folate, and EC
      risk. When serum folate is 10 MUg/l higher than the lowest reference dosage (3.44
      MUg/l), EC decreased risk with an increase in serum folate levels. When folate
      intake is 50 MUg/day higher than the lowest reference dosage (125.21 MUg/day),
      the EC risk is decreased with an increase in folate intake. Finally, the results
      support that folate can promote public health through decreasing EC risk in a
      certain dosage range; otherwise, the protective effects might be reduced.

PMID- 29570106
TI  - The Italian Ministry of Health promotes more than 300 research projects to
      improve cancer prevention, treatment, and prognosis.

PMID- 29570107
TI  - Extensive Myocardial Calcification in Critically Ill Patients.
AB  - OBJECTIVES: To describe an unusual complication on extracorporeal membrane
      oxygenation. DATA SOURCES: Clinical observation. STUDY SELECTION: Case report.
      DATA EXTRACTION: Relevant clinical information. DATA SYNTHESIS: We report the
      cases of three young patients who developed extensive myocardial calcifications
      on prolonged extracorporeal membrane oxygenation support for severe acute
      respiratory distress syndrome with septic cardiomyopathy, postresuscitation
      cardiogenic shock, and septic shock complicating severe acute respiratory
      distress syndrome, respectively. Extensive myocardial calcifications were
      confirmed by echocardiography, CT, and cardiac biopsy. The combination of
      multiple factors, for example, prolonged hemodynamic failure, profound acidosis,
      high vasopressor doses, and renal failure, may lead to this unusual and severe
      complication. CONCLUSIONS: Intensivists should be aware of this rare but rapid
      complication on extracorporeal membrane oxygenation support that may directly
      impact outcome. The precise role of extracorporeal membrane oxygenation support
      in the timing and frequency of new-onset diffuse myocardial calcification
      deserves further investigation.

PMID- 29570108
TI  - Intra-operative lidocaine in the prevention of vomiting after elective
      tonsillectomy in children: A randomised controlled trial.
AB  - BACKGROUND: Postoperative vomiting (POV) is a frequent complication of
      tonsillectomy in children. In adult patients undergoing abdominal surgeries, the
      use of intravenous lidocaine infusion can prevent POV. OBJECTIVE: To evaluate the
      anti-emetic effect of an intravenous lidocaine infusion used as an adjuvant to
      general anaesthesia, in children undergoing elective ear, nose and throat
      surgery. DESIGN: Double-blind, randomised, controlled study. SETTING: Hospital
      based, single-centre study in Chile. PATIENTS: ASA I-II children, aged 2 to 12
      years, scheduled for elective tonsillectomy. INTERVENTION: We standardised the
      induction and maintenance of anaesthesia. Patients were randomly allocated to
      lidocaine (1.5 mg kg intravenous lidocaine over 5 min followed by 2 mg kg h) or
      0.9% saline (at the same rate and volume). Infusions were continued until the end
      of the surgery. MAIN OUTCOME MEASURES: Presence of at least one episode of
      vomiting, retching or both in the first 24 h postoperatively (POV). SECONDARY
      OUTCOMES: Plasma concentrations of lidocaine and postoperative pain. RESULTS:
      Ninety-two children were enrolled. Primary outcome data were available for 91. In
      the Lidocaine group, 28 of 46 patients (60.8%) experienced POV, compared with 37
      of 45 patients (82.2%) in the Saline group [difference in proportions 21.3% (95%
      confidence interval (CI) 2.8 to 38.8), P = 0.024]. The intention-to-treat
      analysis showed that when we assumed that the patient in the Saline group lost to
      follow-up did not have POV, the difference in proportions decreased to 19.6% (95%
      CI, 0.9 to 37.2), with an unadjusted odds ratio of 0.38 (95% CI, 0.15 to 0.97, P
      = 0.044). The odds of having POV were 62% less likely in those patients receiving
      lidocaine compared with patients in the Saline group. The mean lidocaine plasma
      concentration was 3.91 MUg ml (range: 0.87 to 4.88). CONCLUSION: Using an
      intravenous lidocaine infusion as an adjuvant to general anaesthesia decreased
      POV in children undergoing elective tonsillectomy. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01986309.

PMID- 29570109
TI  - Is Patient Knowledge of Glaucoma Improved by Using a Glaucoma Logbook?
AB  - AIMS: Patient-held records are becoming more commonly used in health care,
      particularly in chronic diseases like glaucoma. There is a lack of evidence to
      support their use, however. This study examines the change in knowledge scores
      within a group following the introduction of a newly designed glaucoma logbook.
      METHODS: This analysis uses a test and retest method where patients undergoing
      treatment for glaucoma or ocular hypertension were assessed using a validated
      knowledge questionnaire. They were then given a personalized glaucoma logbook and
      their knowledge scores retested after 4 to 8 weeks. The change in knowledge score
      was examined using a Wilcoxon signed-rank test. RESULTS: A total of 56 patients
      were recruited and 35 completed both questionnaires equating to a 62.5% retention
      rate. The analysis showed a significant increase in the knowledge score attained
      following introduction of the questionnaire (Z=-4.176, P<0.001). CONCLUSIONS: In
      this format, the glaucoma logbook has a positive impact on patient knowledge.
      Further research will be necessary to show if this result is maintained in a
      larger sample group and to investigate whether this improvement in knowledge is
      associated with any improvement in long-term structural and functional outcomes.

PMID- 29570110
TI  - Pain and mortality: mechanisms for a relationship.
AB  - Moderate to severe chronic pain affects 1 in 5 adults and its impact increases
      with age. People with chronic pain that interferes with their lives have an
      increased risk of mortality. Identifying how interfering chronic pain can lead to
      mortality may highlight potential intervention strategies. This study uses a
      novel approach to test whether lifestyle, health, social, and psychological
      factors mediate the relationship between pain and mortality. Survival analyses
      (Cox's proportional hazard modelling and a technique to assess mediation within
      survival models) were conducted on a large population study of adults aged 50
      years or older from the English Longitudinal Study of Ageing (n = 6324). Data
      collected at wave 2 (2004) were used as baseline and follow-up was until 2012.
      The relationship between being "often troubled with pain" and mortality was
      examined. Lifestyle, health, social, and psychological factors were tested as
      potential mediators. The strongest mediating factors for the relationship between
      troubling pain and mortality were functional limitation (hazard ratio 1.31; 95%
      confidence interval 1.20-1.39), symptoms preventing walking quarter of a mile
      (1.45 [1.35-1.58]), physical inactivity (1.14 [1.10-1.20]), and poor self-rated
      health (1.32 [1.23-1.41]). Mediators of the relationship between troubling pain
      and mortality provide targets for preventive health programmes. Interventions to
      improve general health, activity, and function could improve long-term survival
      in patients with this clinical problem.

PMID- 29570111
TI  - Association between aortic knob width and invasively measured aortic pulse
      pressure.
AB  - BACKGROUND: Aortic knob width (AKW), which can be measured easily in simple
      radiography, is associated with the degree of dilatation and tortuosity of the
      aortic arch. Pulsatile stress influences aortic geometry. This study was carried
      out to investigate whether AKW can represent invasively measured aortic pulse
      pressure (APP). METHODS: A total of 252 patients who underwent invasive coronary
      angiography (ICA) for the evaluation of coronary artery disease were enrolled.
      AKW was defined as the perpendicular length from the lateral margin of the main
      bronchus to the most prominent edge of the aortic knob on chest radiography. APP
      was measured at the ascending aorta using a pigtail catheter immediately before
      ICA. RESULTS: When patients were divided into two groups according to the median
      value of APP (69 mmHg), AKW was significantly greater in patients with higher APP
      (>=69 mmHg) than in those with lower APP (<69 mmHg) (40.6+/-4.9 vs. 38.1+/-4.2
      mm, P<0.001). There was a positive linear correlation between APP and AKW
      (r=0.207, P<0.001). In multiple linear regression analysis, the significant
      association between APP and AKW remained even after controlling for the
      confounding factors, including age, sex, height, heart rate, smoking status, left
      ventricular ejection fraction, and left ventricular end-diastolic dimension
      (beta=0.131, P=0.031). CONCLUSION: Greater AKW on chest radiography was
      independently predictive of increased APP in patients undergoing elective ICA.
      The results of this study suggest that AKW can be useful as a simple surrogate
      marker of APP.

PMID- 29570112
TI  - Frontiers in Opioid Pharmacology.

PMID- 29570113
TI  - Potential learning and memory disruptors and enhancers in a simple, 1-day operant
      task in mice.
AB  - The objective of this study was to develop a rapid, 1-day learning and memory
      assay in mice that is sensitive to the effects of compounds that could impair or
      enhance acquisition and retrieval. Swiss-Webster, male mice were placed in
      experimental chambers for a 1-h acquisition session with an intermittent, audible
      tone. If a nose-poke response occurred during the tone, an Ensure water solution
      was presented. After 1 h, the mice returned to the chambers for 2 h. Drugs were
      injected before or after sessions to determine the effects on acquisition and/or
      retrieval. Mice injected with saline learned a nose-poke response as measured by
      decreased latencies to earn 10 reinforcers, increased reinforced response rates,
      and decreased nonreinforced response rates. Scopolamine and acetazolamide
      impaired retrieval of the nose-poke response, whereas ketamine only modestly
      impaired retrieval. Doses of 8-OH-DPAT or the novel carbonic anhydrase activator,
      MAI27, either had no effect or impaired some measures of responding. Neither 8-OH
      DPAT nor MAI27 were able to prevent the modest impairments produced by ketamine.
      The simple, 1-day operant task is a rapid assay that can be used as an initial
      screen to test the effects of learning and memory disruptors and potentially
      enhancers.

PMID- 29570114
TI  - Fatty acid-binding proteins 5 and 7 gene deletion increases sucrose consumption
      and diminishes forced swim immobility time.
AB  - Inhibition and genetic deletion of fatty acid-binding proteins (FABPs) 5 and 7
      have been shown to increase the levels of the endocannabinoid anandamide as well
      as the related N-acylethanolamine's palmitoylethanolamide and oleoylethanolamide.
      This study examined the role of these FABPs on forced-swim (FS) behavior and on
      sucrose consumption in two experiments: (experiment 1) using wild-type (WT) mice
      treated with the FABP inhibitor SBFI26 or vehicle and (experiment 2) using WT and
      FABP5/7 deficient mice. Results from experiment 1 showed that acute treatment
      with SBFI26 did not have any effect on sucrose intake or FS behavior in mice. In
      experiment 2, male and female FABP5/7 deficient mice showed significant increases
      in sucrose consumption (25 and 21%, respectively) compared with their WT
      counterparts. In addition, immobility time during the FS was decreased by 27% in
      both male and female FABP5/7 knockout mice compared with their WT counterparts.
      The fact that such differences were seen between the acute pharmacological
      approach and the genetic approach (gene deletion) of FABP needs to be further
      investigated. The function of FABPs and their specific effects on endocannabinoid
      anandamide, oleoylethanolamide, and palmitoylethanolamide may play an important
      role in the development of reward and mood behaviors and could provide
      opportunities for potential therapeutic targets.

PMID- 29570115
TI  - Crestal Sinus Augmentation in the Presence of Severe Sinus Mucosal Thickening: A
      Report of 3 Cases.
AB  - PURPOSE: In the presence of severe sinus mucosal thickening, the ostium can be
      blocked when the sinus membrane is lifted, causing drainage disturbances and
      sinusitis. Here, we present 3 cases in which maxillary sinus floor elevation was
      performed using a crestal approach in the presence of severe sinus mucosal
      thickening (>10 mm). MATERIALS AND METHODS: The effects of maxillary sinus floor
      elevation using the crestal approach technique on sinus mucosal thickening and
      bone formation in the sinus were evaluated using cone beam computed tomography.
      RESULTS: None of the patients exhibited an increase in sinus membrane thickness.
      No complications were encountered during the follow-up periods, and bone
      formation was observed around the implants at the sinus floor. All implants were
      functioning successfully. CONCLUSIONS: Maxillary sinus floor elevation using the
      crestal approach technique in the presence of severe sinus mucosal thickening
      allows for minimally invasive sinus grafting and simultaneous implant placement
      and does not increase sinus membrane thickness.

PMID- 29570116
TI  - Lead and Influence.

PMID- 29570117
TI  - Development of a Test Battery for Evaluating Speech Perception in Complex
      Listening Environments: Effects of Sensorineural Hearing Loss.
AB  - OBJECTIVE: To evaluate the speech-in-noise performance of listeners with
      different levels of hearing loss in a variety of complex listening environments.
      DESIGN: The quick speech-in-noise (QuickSIN)-based test battery was used to
      measure the speech recognition performance of listeners with different levels of
      hearing loss. Subjective estimates of speech reception thresholds (SRTs)
      corresponding to 100% and 0% speech intelligibility, respectively, were obtained
      using a method of adjustment before objective measurement of the actual SRT
      corresponding to 50% speech intelligibility in every listening condition.
      RESULTS: Of the seven alternative listening conditions, two conditions, one
      involving time-compressed, reverberant speech (TC+Rev), and the other (N0Spi)
      having in-phase noise masker (N0) and out-of-phase target (Spi), were found to be
      substantially more sensitive to the effect of hearing loss than the standard
      QuickSIN test. The performance in these two conditions also correlated with self
      reported difficulties in attention/concentration during speech communication and
      in localizing the sound source, respectively. Hearing thresholds could account
      for about 50% or less variance in SRTs in any listening condition. Subjectively
      estimated SRTs (SRTs corresponding to 0% and 100% speech intelligibility) were
      highly correlated with the objective SRT measurements (SRT corresponding to 50%
      speech intelligibility). CONCLUSIONS: A test battery that includes the TC+Rev and
      the N0Spi conditions would be useful in identifying individuals with hearing loss
      with speech-in-noise deficits in everyday communication.

PMID- 29570118
TI  - Comparison of the Lubricity and Surface Roughness of 5 Cosmetic Contact Lenses.
AB  - OBJECTIVES: Cosmetic contact lenses are increasingly popular because of their eye
      enhancing cosmetic benefits. The pigment particles used in these lenses can
      impact lens surface characteristics. This article examines the surface
      characteristics and the differences between the clear and the pigmented regions
      among five limbal ring design lenses. METHODS: Scanning electron microscopy was
      used to determine the location and depth of the pigment particles from the lens
      surface. The coefficient of friction (CoF) was determined with a Basalt-MUST
      microtribometer at clear and pigmented regions on either the front or the back
      surface. Atomic force microscopy was used to determine the surface roughness of
      each lens in root-mean-square (RMS) units at clear and pigmented regions. A
      linear mixed model for repeated measures was used for the analysis of the CoF and
      RMS roughness to compare all lenses. RESULTS: Four lens types had pigments
      exposed on the surface and one lens type had pigment fully enclosed. The CoF
      difference between clear and pigmented regions were similar and not statistically
      significant (P=0.0124) for the lens type with pigments enclosed, whereas the CoF
      difference for the other four lens types showed statistically significant
      difference (P<0.0001). CONCLUSIONS: Of the lenses tested here, cosmetic contact
      lenses with pigments enclosed in the lens matrix provided a more consistent
      surface between clear and pigmented regions compared with lenses that had exposed
      pigments.

PMID- 29570119
TI  - H3K4 Methylation Regulates LPS-Induced Proinflammatory Cytokine Expression and
      Release in Macrophages.
AB  - Histone methylation is an important epigenetic mechanism that plays an essential
      role in regulating gene expression in mammalian cells. To understand its
      influence on inflammation, methylation of H3K4, H3K9, H3K36, H3K79, and H4K20,
      the most common histones methylated in the inflammatory response, was analyzed in
      murine RAW264.7 cells and bone marrow-derived macrophages (BMDMs) upon LPS
      stimulation. LPS stimulation resulted in enhanced methylation at H3K4 and H3K9 in
      both RAW264.7 and BMDMs. To further confirm whether LPS-stimulated H3K4me2 and
      H3K9me2 were responsible for subsequent proinflammatory cytokine expression, the
      recruitment of H3K4me2 and H3K9me2 at the promoters of IL-6 and TNF-alpha was
      assessed. H3K4me2, but not H3K9me2, was enriched at the promoters of both IL-6
      and TNF-alpha. Furthermore, LPS-stimulated gene expression and release of IL-6
      and TNF-alpha were markedly suppressed in macrophages by MTA, a specific
      inhibitor of H3K4 methylation. These results demonstrate that histone
      methylation, in particular H3K4me2, plays a critical role in the regulation of
      LPS-induced expression and release of IL-6 and TNF-alpha.

PMID- 29570120
TI  - Mortality Associated With Emergency Department Boarding Exposure: Are There
      Differences Between Patients Admitted to ICU and Non-ICU Settings?
AB  - BACKGROUND: Emergency Department (ED) boarding threatens patient safety. It is
      unclear whether boarding differentially affects patients admitted to intensive
      care units (ICUs) versus non-ICU settings. RESEARCH DESIGN AND SUBJECTS: We
      performed a 2-hospital, 18-month, cross-sectional, observational, descriptive
      study of adult patients admitted from the ED. We used Kaplan-Meier estimation and
      Cox Proportional Hazards regression to describe differences in boarding time
      among patients who died during hospitalization versus those who survived,
      controlling for covariates that could affect mortality risk or boarding exposure,
      and separately evaluating patients admitted to ICUs versus non-ICU settings.
      MEASURES: We extracted age, race, sex, time variables, admission unit, hospital
      disposition, and Elixhauser comorbidity measures and calculated boarding time for
      each admitted patient. RESULTS: Among 39,781 admissions from the EDs (21.3% to
      ICUs), non-ICU patients who died in-hospital had a 1.2-fold risk (95% confidence
      interval, 1.03-1.36; P=0.016) of having experienced longer boarding times than
      survivors, accounting for covariates. We did not observe a difference among
      patients admitted to ICUs. CONCLUSIONS: Among non-ICU patients, those who died
      during hospitalization were more likely to have had incrementally longer boarding
      exposure than those who survived. This difference was not observed for ICU
      patients. Boarding risk mitigation strategies focused on ICU patients may have
      accounted for this difference, but we caution against interpreting that boarding
      can be safe. Segmentation by patients admitted to ICU versus non-ICU settings in
      boarding research may be valuable in ensuring that the safety of both groups is
      considered in hospital flow and boarding care improvements.

PMID- 29570121
TI  - Progression of Adjacent-level Degeneration After Lumbar Total Disc Replacement:
      Results of a Post-hoc Analysis of Patients With Available Radiographs From a
      Prospective Study With 5-year Follow-up.
AB  - STUDY DESIGN: Post-hoc analysis of 5-year follow-up data from a randomized,
      multicenter trial. OBJECTIVE: The aim of this study was to investigate the
      incidence of progression in radiographic adjacent-level degeneration (DeltaALD)
      from preoperative assessment to 5 years after total disc replacement (TDR) and
      the relationship of these changes with range of motion and clinical adjacent
      level disease. A secondary objective was to compare adjacent-level degeneration
      (ALD) outcomes between TDR and fusion. SUMMARY OF BACKGROUND DATA: Fusion is
      associated with high rates of ALD in symptomatic lumbar disc degeneration. TDR
      may reduce this risk. METHODS: In total, 175 patients with single-level,
      symptomatic, lumbar disc degeneration who had received activL or ProDisc-L and
      had a preoperative and 5-year postoperative radiograph available were included.
      Over 5-year follow-up, DeltaALD was defined as an increase in ALD of >=1 grade
      and clinical ALD was defined as surgical treatment at the level adjacent to an
      index TDR. Matching-adjusted indirect comparisons were conducted to compare ALD
      outcomes after TDR (current trial) with those after fusion (published trial).
      RESULTS: At 5-year follow-up, 9.7% (17/175) of TDR patients had DeltaALD at the
      superior level. In patients with preoperative ALD at the superior level, most
      (88% [23/26]) showed no radiographic progression over 5 years. The rate of
      clinical ALD was 2.3% (4/175) and none of these patients had ALD at baseline. For
      each degree of range of motion gained at the TDR level, there was a consistent
      decrease in the percentage of patients with DeltaALD. After matching and
      adjustment of baseline characteristics, TDR had a significantly lower likelihood
      of DeltaALD than fusion (odds ratio 0.32; 95% confidence interval 0.13, 0.76).
      CONCLUSION: The rates of DeltaALD and clinical ALD in this TDR population were
      similar to those previously reported in the literature for TDR at 5-year follow
      up. TDR had a significantly lower rate of DeltaALD than fusion. LEVEL OF
      EVIDENCE: 3.

PMID- 29570123
TI  - Artefacts in occupational stress research.

PMID- 29570122
TI  - Letter to Editor About the Article "Hills J, Sivaganesan A, Khan I, et al. Causes
      and Timing of Unplanned 90-day Readmissions Following Spine Surgery. Spine (Phila
      Pa 1976). 2017 Dec 26. doi: 10.1097/BRS.0000000000002535."

PMID- 29570124
TI  - Bias in occupational stress research - Authors' reply.

PMID- 29570125
TI  - Improvement to visualization of nodes in breast cancer patients following audit:
      are we seeing the problem?
AB  - Successful localization of nodes in breast cancer patients depends upon the
      effectiveness of the lymphoscintigraphy technique employed. A benefit of
      performing imaging as part of this procedure is that it allows sites to audit
      their technique. An audit of breast cancer patients at the Glasgow Royal
      Infirmary (GRI) hospital showed nodes to be visualized in only 81% of patients.
      Current guidelines state that nodes should be seen in more than 95% of patients.
      A period of investigation and review led to changes being made to the injection
      and imaging technique employed at the GRI site. Following these changes a re
      audit was performed that showed that the node visualization rate has successfully
      been increased to 97%, thereby meeting the standards set in the guidelines. This
      technical note details the results of the initial audit and re-audit, and
      explains the investigation and changes made to clinical procedures at the GRI
      site to improve the node visualization rate. The challenges that can occur when
      performing breast sentinel node procedures are also discussed.

PMID- 29570126
TI  - The Association of Abdominal Striae With Pelvic Organ Prolapse.
AB  - OBJECTIVE: Our objective was to estimate the prevalence of abdominal wall striae
      among women with and without pelvic organ prolapse (POP) in a population with
      pelvic floor disorders. METHODS: This cross-sectional study included nonpregnant
      women with urinary incontinence and POP presenting to a tertiary urogynecology
      practice between December 2012 and August 2013. Participants completed a
      nonvalidated questionnaire about striae, and the degree of abdominal wall striae
      was quantified on physical examination. Baseline demographics, clinical
      characteristics, and Pelvic Organ Prolapse Quantification (POP-Q) measurements
      were recorded. RESULTS: One hundred thirty-two women were approached for
      participation, of which 110 (83%) completed study questionnaires. Of these 110,
      59 had POP defined at POP-Q stages 2-4, whereas 51 had normal pelvic support, POP
      Q stages 0-1. The mean (SD) age was 55.5 (12) years, and most (78/110) were
      sexually active. Women with POP were more parous than women without POP (median 2
      vs 1, respectively; P = 0.03). However, there was no difference in medical
      comorbidities, smoking status, or steroid use between groups (P > 0.05). More
      women with POP reported striae (42/59 [71%] vs 23/51 [45%], P = 0.006) and had
      quantifiable abdominal wall striae compared with women with normal support (39/59
      [66%] vs 22/51 [44%], P = 0.02). On multivariate logistic regression, women with
      POP were 2.5 times more likely to have striae compared with women without POP
      after adjusting for skin type and smoking status (odds ratio, 2.5; 95% confidence
      interval, 1.03-6.06; P = 0.04). CONCLUSION: Women with POP are more likely to
      have striae compared with women without POP.

PMID- 29570127
TI  - Successful Treatment of Paradoxical Puborectalis Contraction and Intractable
      Anorectal Pain With Sacral Neuromodulation.
AB  - BACKGROUND: Paradoxical puborectalis contraction (PPC) is a syndrome of
      obstructed defecation associated with a cluster of complaints including rectal
      pain, incomplete evacuatory sensation, prolonged repetitive straining with bowel
      movements, and the need for digital manipulation. Traditional treatment has
      yielded mixed results. CASE: We present a case of PPC successfully treated with
      staged sacral neuromodulation and review her diagnostic features, medical
      regimen, and prior unsuccessful interventions tried. Symptoms were analyzed using
      a visual analog scale pain score (0-10). Criteria to progress to implantation of
      the pulse generator included a pain score less than 3 during test stimulation
      and/or greater than 50% decrease in the pain score compared to baseline.Our
      patient had a pain score of 0 (baseline 8) with stage 1 sacral neuromodulation.
      In addition, she had dramatic relief in her straining with bowel movements and
      need for digital manipulation. Her pulse generator was implanted after a 2-week
      trial, and she has experienced a lasting improvement at her follow-up of 2 years.
      CONCLUSIONS: Sacral neuromodulation is an established therapy for overactive
      bladder syndrome, urinary retention, and fecal incontinence. In urology, the use
      of sacral neuromodulation has been described to benefit some patients with pelvic
      floor pain. Sacral neuromodulation can be a successful treatment for PPC and
      functional anorectal pain with resulting improvement in quality of life without
      the sequelae of an invasive and irreversible surgery.

PMID- 29570128
TI  - Small Subset of Adenoid Cystic Carcinoma of the Skin Is Associated With
      Alterations of the MYBL1 Gene Similar to Their Extracutaneous Counterparts.
AB  - Adenoid cystic carcinoma (ACC) of the skin is a rare malignant neoplasm
      histologically identical to homonymous tumors in other organs. Cutaneous ACC has
      been found to harbor MYB gene activations, either through MYB chromosomal
      abnormalities or by generation of the MYB-NFIB fusion. In salivary gland ACC, in
      addition to the MYB gene, alterations in MYBL1, the gene closely related to MYB,
      have been reported. We studied 10 cases of cutaneous ACC (6 women, 4 men; and age
      range 51-83 years) for alterations in the MYB, NFIB, and MYBL1 genes, using FISH
      and PCR. MYB break-apart and NFIB break-apart tests were positive in 4 and 5
      cases, respectively. MYB-NFIB fusions were found in 4 cases. The break of MYBL1
      was found in 2 cases, and in one of them, the NFIB break-apart probe was
      positive, strongly indicating a MYBL1-NFIB fusion. In 2 cases, the MYB break
      apart test was positive, whereas no MYB-NFIB was detected, strongly suggesting
      another fusion partner. It is concluded that MYBL1 alterations are detected in
      primary cutaneous ACC but are apparently less common compared with MYB and NFIB
      alterations.

PMID- 29570129
TI  - CD34 and BerEP4 Are Helpful to Distinguish Basaloid Tricholemmoma From Basal Cell
      Carcinoma.
AB  - Tricholemmoma, a benign follicular neoplasm with outer root sheath
      differentiation, typically comprises clear or pale cells, and when multiple is
      pathognomic of Cowden's syndrome. The tumor is probably underrecognized and in
      basaloid examples can be difficult to distinguish from basal cell carcinoma
      (BCC). We studied 55 tricholemmomas (including 15 basaloid cases) and compared
      immunohistochemical profile with nodular BCC from our archives. Basaloid and non
      basaloid tricholemmomas had similar staining characteristics. BerEP4 was focally
      positive (range 10%-20%) in only 3/39 (7.7%) tricholemmomas compared with
      widespread positivity in BCC (90.8%, 139 of 151 cases with >=50% tumor area
      stained). CD34 was expressed, usually focally (median 20%, range 10%-90%), in
      52/53 (98.1%) tricholemmomas and was negative in all 21 BCCs stained. EMA
      staining lacked sensitivity or specificity in differentiating tricholemmoma from
      BCC. Five or more Merkel cells were found in 7/17 (40.1%) tricholemmomas and 1/23
      (4.3%) nodular BCCs studied. In summary, immunohistochemistry is helpful in
      distinction between tricholemmoma, including difficult basaloid examples (BerEP4
      negative or focal, CD34 positive) compared with BCC (BerEP4 widespread in most
      cases, CD34 negative). The presence of 5 or more Merkel cells is a relatively
      specific but not a particularly sensitive discriminator.

PMID- 29570130
TI  - Cholesterol Clefts in Basal Cell Carcinoma: An Under-Recognized Association.
AB  - Cholesterol clefts have rarely been described in cutaneous tumors other than
      lipid-rich tumors. However, they seem to be a relatively common phenomenon in
      basal cell carcinoma (BCC). This study was undertaken to determine the frequency
      of cholesterol cleft deposition in BCCs, and to identify associated
      histopathologic and clinical features. Twenty-eight of 249 BCC cases reviewed
      showed features of cholesterol cleft. Mean disease duration in those with
      cholesterol cleft was significantly longer than in those without cholesterol
      cleft (5.58 vs. 3.29 years, respectively; P = 0.013). Sex and age distributions,
      and average tumor longest diameter (11.6 vs. 9.41 mm) were no different for those
      with or without cholesterol clefts. The most common anatomical location was the
      nose in both those with and without cholesterol clefts. BCCs without cholesterol
      clefts more frequently involved the periauricular and perioral areas, and areas
      other than the head and neck, such as the trunk and lower extremities (P =
      0.087). Histopathologic features of necrosis (26/28, 92.86%), keratinization
      (19/28, 67.86%), and pigment deposition (18/28, 64.29%) were found to be
      associated with cholesterol clefts. Cholesterol clefts were intratumorally
      located in 27/28 cases (96.43%), and stromally located in 2 cases (7.14%);
      intravascularly located cholesterol clefts were observed in no case. In
      conclusion, this study shows that cholesterol clefts are relatively common in
      BCC, and suggests that cholesterol crystal deposition could be associated with
      longer disease duration and microtrauma.

PMID- 29570131
TI  - Painful Piezogenic Pedal Papules in a Female Babysitter: A Case-Based Review.

PMID- 29570132
TI  - Xanthomatous Cells in Cutaneous Graft-Versus-Host Disease Biopsies: A Clue for
      the Diagnosis of Hepatic Graft-Versus-Host Disease.
AB  - Graft-versus-host disease (GVHD) is one of the most common and serious
      complications of hematopoietic stem-cell transplantation that mainly affects the
      skin, gastrointestinal tract, and liver. Hepatic GVHD is associated with high
      morbidity and mortality, and its diagnosis can be especially challenging because
      of nonspecific clinical signs and symptoms. It must be suspected in patients with
      elevated liver enzymes and cholestasis, especially in those with a history of
      preceding skin rash and diarrhea. We describe 3 patients with cutaneous and
      hepatic GVHD that presented with severe hypercholesterolemia and
      hypertriglyceridemia, and no xanthomatous macular lesions, in which cutaneous
      biopsies revealed the presence of xanthomatous dermal histiocytes. We propose
      that the presence of these xanthomatous cells in skin biopsies from patients with
      cutaneous GVHD could be a dermatopathological clue for the diagnosis of hepatic
      GVHD.

PMID- 29570133
TI  - Small Vessel Vasculitis in Herpes Zoster-Discussion of Current Aspects of
      Varicella Zoster Virus Vasculopathy.
AB  - Varicella zoster virus (VZV) vasculopathy was initially described as herpes
      zoster ophthalmicus with contralateral hemiplegia in 1896. VZV is able to infect
      endothelial cells directly, leading to a thickened intima and vascular remodeling
      due to inflammation. Therefore, a spectrum of vasculopathies is induced, ranging
      from a discrete capillaritis-to-granulomatous vasculitis and obliterative
      angiitis. Cutaneous vasculitic changes sui generis with leukocytoclasia, cell
      debris, vascular damage, and endothelial swelling are very rare feature of
      herpetic infections in skin biopsies. We report an immunocompetent patient who
      presented with a rare form of cutaneous VZV infection of the upper leg
      characterized by vasculitic changes of the small vessels without typical herpetic
      epidermal features or neural involvement. Intriguingly, the vasculitis appeared
      prior to the characteristic vesicular rush without any pain symptoms. Because VZV
      can cause vasculopathic damage mainly within the central nervous system in
      immunocompetent and immunosuppressed patients, we recommend continuous clinical
      controls to recognize central symptoms that are related to VZV vasculopathy or
      giant cell arteriitis.

PMID- 29570134
TI  - Ecchymotic Nodule on the Scalp: Challenge.

PMID- 29570135
TI  - Diffuse Papular Rash in a Young Woman: Challenge.

PMID- 29570136
TI  - Effectiveness of an Educational Intervention to Increase Human Papillomavirus
      Knowledge in High-Risk Minority Women.
AB  - OBJECTIVES: The aims of the study were to evaluate human papillomavirus (HPV) and
      cervical cancer knowledge in a population at high risk for cervical cancer and to
      determine whether knowledge and attitudes toward HPV vaccination improve after
      educational intervention. MATERIALS AND METHODS: This pre-post survey design
      study was conducted at the John H. Stroger Hospital of Cook County colposcopy
      clinic. An HPV knowledge and awareness survey was given to participants before
      their clinical encounter. Afterward, participants watched an educational video
      and repeated the survey, which was administered again at the follow-up visit.
      Knowledge scores and acceptability of HPV vaccination were compared across all
      surveys. RESULTS: Among the 104 participants who completed baseline and immediate
      postintervention surveys, the average baseline score was 9.6 of 20. Knowledge
      scores improved after the educational intervention (mean = 14.1, p < .0001) and
      remained elevated in the 44 participants that completed long-term follow-up (mean
      = 13.5, p < .0001). Acceptability of HPV vaccination for participants themselves
      increased from 47.1% to 76% (p < .0001) and for children/grandchildren increased
      from 30.8% to 71.2% (p < .0001) after the intervention. Overall, women were
      worried about HPV and cervical cancer for themselves and their
      children/grandchildren at baseline. However, the intervention improved
      perceptions about HPV vaccination cost, safety, adverse effects, and efficacy.
      CONCLUSIONS: Knowledge of HPV, cervical cancer, and HPV vaccination is low in
      this high-risk population and may improve with a simple educational intervention.
      Increased knowledge was associated with an increase in vaccine acceptability and
      improved perceptions about HPV vaccination. Educational interventions targeted
      toward high-risk women are necessary to decrease cervical cancer incidence and
      mortality.

PMID- 29570137
TI  - Statistical Modeling for Quality Assurance of Human Papillomavirus DNA Batch
      Testing.
AB  - OBJECTIVES: Our objective was to simulate the distribution of human
      papillomavirus (HPV) DNA test results from a 96-well microplate assay to identify
      results that may be consistent with well-to-well contamination, enabling programs
      to apply specific quality assurance parameters. MATERIALS AND METHODS: For this
      modeling study, we designed an algorithm that generated the analysis population
      of 900,000 to simulate the results of 10,000 microplate assays, assuming discrete
      HPV prevalences of 12%, 13%, 14%, 15%, and 16%. Using binomial draws, the
      algorithm created a vector of results for each prevalence and reassembled them
      into 96-well matrices for results distribution analysis of the number of positive
      cells and number and size of cell clusters (>=2 positive cells horizontally or
      vertically adjacent) per matrix. RESULTS: For simulation conditions of 12% and
      16% HPV prevalence, 95% of the matrices displayed the following characteristics:
      5 to 17 and 8 to 22 total positive cells, 0 to 4 and 0 to 5 positive cell
      clusters, and largest cluster sizes of up to 5 and up to 6 positive cells,
      respectively. CONCLUSIONS: Our results suggest that screening programs in regions
      with an oncogenic HPV prevalence of 12% to 16% can expect 5 to 22 positive
      results per microplate in approximately 95% of assays and 0 to 5 positive results
      clusters with no cluster larger than 6 positive results. Results consistently
      outside of these ranges deviate from what is statistically expected and could be
      the result of well-to-well contamination. Our results provide guidance that
      laboratories can use to identify microplates suspicious for well-to-well
      contamination, enabling improved quality assurance.

PMID- 29570138
TI  - Vulvovaginal Disease Education in Canadian and American Gynecology Residency
      Programs: A Survey of Program Directors.
AB  - OBJECTIVE: The aims of the study were to assess and describe the current
      vulvovaginal curriculum in gynecology residency training programs in Canada and
      the United States and to compare this with national training objectives.
      MATERIALS AND METHODS: A 22-question electronic survey was sent to 252 gynecology
      program directors in Canada and the United States between September 2015 and July
      2016 using the platform SurveyMonkey.com. Survey responses were entered into SPSS
      Version 23, and analysis was performed using descriptive statistics. RESULTS:
      Overall, 58 (23%) of 252 programs directors responded. Nearly all of the sites
      provided formal teaching on pain disorders (54/58, 93%), vulvar dermatoses
      (54/58, 93%), and vulvovaginal infections (57/58, 98%). Exposure to vulvovaginal
      clinics varied widely. On average, program directors estimated that residents
      spend a median of 10 hours (0-200) in vulvar pain clinics, 9 hours (0-200) in
      dermatology clinics, and 50 hours (0-480) in colposcopy clinics during residency
      training. Most program directors (53/57, 93%) believed that all general
      gynecologists should be able to manage vulvar disorders in practice. Reported
      obstacles to treating vulvar disorders included lack of training (41/58, 71%) and
      lack of interest (35/58, 60%). CONCLUSIONS: While most residency programs
      provided formal education on vulvovaginal diseases, clinical exposure is
      extremely variable between sites. When it is not possible to increase clinical
      exposure to vulvovaginal disorders, traditional training methods (lectures,
      textbooks) should be supplemented with online modules and other means of learning
      to improve resident knowledge of vulvovaginal diseases.

PMID- 29570139
TI  - Prevalence of Suspected Nonalcoholic Fatty Liver Disease in Lean Adolescents in
      the United States.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects
      referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of
      NAFLD in lean adolescents in the United States (US). METHODS: Cross sectional
      data from 1482 lean subjects (body mass index <85th percentile) ages between 12
      and 18 years, who were enrolled in the National Health and Examination Survey
      during the 2005 to 2014 cycles were included. We defined suspected NAFLD as
      alanine aminotransferase >25.8 U/L for boys and >22.1 U/L for girls;
      hypertriglyceridemia as triglycerides >=150 mg/dL; low HDL as HDL <40 mg/dL and
      insulin resistance (IR) as homeostatic model assessment of IR >=3. RESULTS: The
      mean weighted prevalence of suspected NAFLD among lean adolescents during 2005 to
      2014 cycles was 8% (95% CI 6.2-9.9). Lean subjects with suspected NAFLD were
      significantly older compared with lean non-NAFLD subjects (15.5 vs 15 years, P
      value <0.05). Low HDL (15.5% vs 6.8%; P value 0.016) and hypertriglyceridemia
      (10% vs 3.9%; P value 0.028) were also found to be more common among lean NAFLD
      subjects compared with their non-NAFLD counterparts. Presence of IR increased the
      risk of having suspected NAFLD by 4-fold among lean adolescents. Non-Hispanic
      black lean adolescents were less likely to have suspected NAFLD compared with non
      Hispanic white lean adolescents. CONCLUSIONS: The estimated prevalence of
      suspected NAFLD among lean adolescents in the US was found to be 8% with evidence
      of metabolic derangements such as low HDL, hypertriglyceridemia, and IR.

PMID- 29570140
TI  - Endoscopic Treatment of Duodenal Web in Association With Annular Pancreas in an
      Infant.

PMID- 29570141
TI  - The American Organization of Nurse Executives and American Hospital Association
      Initiatives Work to Combat Violence.
AB  - Violence affecting healthcare workers and healthcare organizations continues to
      be a serious safety issue. In this Leadership Perspectives column, Karen Wray, an
      American Organization of Nurse Executives (AONE) member who has experienced a
      mass causality incident 1st hand, outlines AONE's continuing work to promote
      safety and combat violence. She discusses recent work on violence issues by the
      American Hospital Association, AONE's parent organization.

PMID- 29570142
TI  - So You're Thinking About the Journey to Magnet(r) Recognition...?
AB  - The Director of the Magnet Recognition Program(r) presents a list of resources
      available to organizations either on the journey to Magnet(r) or contemplating
      setting this prestigious designation of nursing excellence as a goal.

PMID- 29570143
TI  - DAISY Nurses-Recognizing Clinical Expertise Through Certification.
AB  - The DAISY Foundation is dedicated to recognizing nurses who provide
      compassionate, skilled, and extraordinary nursing care. Nominations for The DAISY
      Award are typically submitted in the form of a story. Stories are an opportunity
      to share with others what compassionate and extraordinary nursing care looks like
      and to recognize the individual nurses who provide that care. Clinical competence
      delivered with compassion is a hallmark of DAISY Award recipients. Professional
      certification provides an additional form of recognition of a nurse's clinical
      competence.

PMID- 29570144
TI  - The Imperative of Solving Nurses' Usability Problems With Health Information
      Technology.
AB  - BACKGROUND: Health information technology (IT) usability issues are a key concern
      for nurse executives and nurses. OBJECTIVES: The aims of this study are to
      understand usability pain points faced by nurses regarding the use of health IT,
      identify their impact and importance, discuss responsibilities, and develop
      possible solutions to improve the health IT-user experience for nurses. METHODS:
      Twenty-seven experts were interviewed including nursing leaders, informaticists,
      executives, engineers, researchers, and human factors experts across acute care,
      long-term care, and vendor settings. Semistructured questions guided the
      interviews, and content analysis was used to identify themes. RESULTS: Four
      themes emerged: 1) user experience pain points, 2) importance of the issues, 3)
      the responsibility gap, and 4) acting on usability issues. CONCLUSION: Nurses
      continue to endure significant health IT-usability issues that negatively impact
      patients, nurses, and healthcare organizations. Solutions include enhancing the
      voice of nursing at the national and local levels, creating a digital strategy
      for nursing, providing incentives to improve usability in health IT, and
      accelerating the understanding of nurses' work intended to inform and translate
      nurses' work into health IT design.

PMID- 29570145
TI  - The Effects of Social Influence on Nurses' Hand Hygiene Behaviors.
AB  - OBJECTIVE: The aim of this article is to describe the associations of nurses'
      hand hygiene (HH) attitudes, subjective norms, and perceived behavioral control
      with observed and self-reported HH behavior. BACKGROUND: Hand hygiene is an
      essential strategy to prevent healthcare-associated infections. Despite
      tremendous efforts, nurses' HH adherence rates remain suboptimal. METHODS: This
      quantitative descriptive study of ICU nurses in the southeastern United States
      was guided by the theory of planned behavior. The self-administered Patient
      Safety Opinion Survey and iScrub application, which facilitates observation,
      comprised the data set. RESULTS: Nurses' observed HH median was 55%; tendency to
      self-report was a much higher 90%. Subjective norm and perceived control scores
      were associated with observed and self-reported HH (P < .05) but not attitude
      scores or reports of intention. CONCLUSIONS: Nurses' subjective norm and
      perceived control are associated with observed and self-reported HH performance.
      Healthcare workers overestimate their HH performance. Findings suggest future
      research to explore manipulators of these variables to change nurses' HH
      behavior.

PMID- 29570146
TI  - Carolina Care at University of North Carolina Health Care: Implementing a Theory
      Driven Care Delivery Model Across a Healthcare System.
AB  - Patient satisfaction is a key component of healthcare organizations' performance.
      Providing a consistent, positive patient experience across a system can be
      challenging. This article describes an organization's approach to achieving this
      goal by implementing a successful model developed at the flagship academic
      healthcare center across an 8-hospital system. The Carolina Care at University of
      North Carolina Health Care initiative has resulted in substantive qualitative and
      quantitative benefits including higher patient experience scores for both overall
      rating and nurse communication.

PMID- 29570147
TI  - Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of
      the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric
      Gastroenterology, Hepatology and Nutrition.
AB  - BACKGROUND AND AIMS: A growing body of evidence supports the need for detailed
      attention to nutrition and diet in children with inflammatory bowel disease
      (IBD). We aimed to define the steps in instituting dietary or nutritional
      management in light of the current evidence and to offer a useful and practical
      guide to physicians and dieticians involved in the care of pediatric IBD
      patients. METHODS: A group of 20 experts in pediatric IBD participated in an
      iterative consensus process including 2 face-to-face meetings, following an open
      call to Nutrition Committee of the European Society of Pediatric
      Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition
      Committee. A list of 41 predefined questions was addressed by working subgroups
      based on a systematic review of the literature. RESULTS: A total of 53 formal
      recommendations and 47 practice points were endorsed with a consensus rate of at
      least 80% on the following topics: nutritional assessment; macronutrients needs;
      trace elements, minerals, and vitamins; nutrition as a primary therapy of
      pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and
      dietary compounds and the risk of IBD. CONCLUSIONS: This position paper
      represents a useful guide to help the clinicians in the management of nutrition
      issues in children with IBD.

PMID- 29570148
TI  - Errata.

PMID- 29570149
TI  - Errata.

PMID- 29570150
TI  - Cost-Effectiveness Research in Anesthesiology.
AB  - Perioperative interventions aimed at decreasing costs and improving outcomes have
      become increasingly popular in recent years. Anesthesiologists are often faced
      with a choice among different treatment strategies with little data available on
      the comparative cost-effectiveness. We performed a systematic review of the
      English language literature between 1980 and 2014 to identify cost-effectiveness
      analyses of anesthesiology and perioperative medicine interventions. We excluded
      interventions related to critical care or pediatric anesthesiology, and articles
      on interventions not normally ordered or performed by anesthesiologists. Of the
      >5000 cost-effectiveness analyses published to date, only 28 were applicable to
      anesthesiology and perioperative medicine and met inclusion criteria.
      Multidisciplinary interventions were the most cost-effective overall; 8 of 8
      interventions were "dominant" (improved outcomes, reduced cost) or cost
      effective, including accelerated, standardized perioperative recovery pathways,
      and perioperative delirium prevention bundles. Intraoperative measures were
      dominant in 3 of 5 cases, including spinal anesthesia for benign abdominal
      hysterectomy. With regard to prevention of perioperative infection, methicillin
      resistant Staphylococcus aureus (MRSA) decolonization was dominant or cost
      effective in 2 of 2 studies. Three studies assessing various antibiotic
      prophylaxis regimens had mixed results. Autologous blood donation was not found
      to be cost-effective in 5 of 7 studies, and intraoperative cell salvage therapy
      was also not cost-effective in 2 of 2 reports. Overall, there remains a paucity
      of cost-effectiveness literature in anesthesiology, particularly relating to
      intraoperative interventions and multidisciplinary perioperative interventions.
      Based on the available studies, multidisciplinary perioperative optimization
      interventions such as accelerated, standardized perioperative recovery pathways,
      and perioperative delirium prevention bundles tended to be most cost-effective.
      Our review demonstrates that there is a need for more rigorous cost-effective
      analyses in many areas of anesthesiology and that anesthesiologists should
      continue to lead collaborative, multidisciplinary efforts in perioperative
      medicine.

PMID- 29570151
TI  - Incidence and Risk Factors for Chronic Postoperative Opioid Use After Major Spine
      Surgery: A Cross-Sectional Study With Longitudinal Outcome.
AB  - BACKGROUND: Chronic opioid use is a significant public health concern. Surgery is
      a risk factor for developing chronic opioid use. Patients undergoing major spine
      surgery frequently are prescribed opioids preoperatively and may be at risk for
      chronic opioid use postoperatively. The aim of this study was to investigate the
      incidence of and perioperative risk factors associated with chronic opioid use
      after major spine surgery. METHODS: The records of patients who underwent
      elective major spine surgery at the University of Virginia between March 2011 and
      February 2016 were retrospectively reviewed. The primary outcome was chronic
      opioid use through 12 months postoperatively. Demographic data, medical
      comorbidities, preoperative pain scores, and medication use including daily
      morphine-equivalent (ME) dose, intraoperative use of lidocaine and ketamine,
      estimated blood loss, postoperative pain scores and medication use, and
      postoperative opioid use were collected. Logistic regression models were used to
      examine factors associated with chronic opioid use. RESULTS: Of 1477 patient
      records reviewed, 412 patients (27.9%) were opioid naive and 1065 patients
      (72.3%) used opioids before surgery. Opioid data were available for 1325
      patients, while 152 patients were lost to 12-month follow-up and were excluded.
      Of 958 preoperative opioid users, 498 (52.0%) remained chronic users through 12
      months. There was a decrease in opioid dosage (mg ME) from preoperative to 12
      months postoperatively with a mean difference of -14.7 mg ME (standard deviation,
      1.57; 95% confidence interval [CI], -17.8 to -11.7). Among 367 previously opioid
      naive patients, 67 (18.3%) became chronic opioid users. Factors associated with
      chronic opioid use were examined using logistic regression models. Preoperative
      opioid users were nearly 4 times more likely to be chronic opioid users through
      12 months than were opioid-naive patients (odds ratio, 3.95; 95% CI, 2.51-6.33; P
      < .001). Mean postoperative pain score (0-10) was associated with increased odds
      of chronic opioid use (odds ratio for a 1 unit increase in pain score 1.25, 95%
      CI, 1.13-1.38; P < .001). Use of intravenous ketamine or lidocaine was not
      associated with chronic opioid use through 12 months. CONCLUSIONS: Greater than
      70% of patients presenting for major spine surgery used opioids preoperatively.
      Preoperative opioid use and higher postoperative pain scores were associated with
      chronic opioid use through 12 months. Use of ketamine and lidocaine did not
      decrease the risk for chronic opioid use. Surveillance of patients for these
      factors may identify those at highest risk for chronic opioid use and target them
      for intervention and reduction strategies.

PMID- 29570152
TI  - Opioid Use Disorders and the Risk of Postoperative Pulmonary Complications.
AB  - BACKGROUND: As the rate of opioid use disorders continues to rise, perioperative
      physicians are increasingly faced with the challenge of providing analgesia to
      these patients after surgery. Due to the likelihood of opioid dose escalation in
      the perioperative period, we hypothesized that opioid-dependent patients would be
      at increased risk for postoperative pulmonary complications. METHODS: A
      retrospective cross-sectional analysis of patients undergoing 6 representative
      elective surgical procedures was performed using the Nationwide Inpatient Sample
      from 2002 to 2011. The primary outcome was a composite including prolonged
      mechanical ventilation, reintubation, and acute respiratory failure. Secondary
      outcomes were length of stay, in-hospital mortality, and total hospital costs.
      Both multivariable logistic regression and propensity score matching were used to
      determine the impact of opioid use disorder on outcomes. RESULTS: The total
      sample-weighted cohort consisted of 7,533,050 patients. Patients with opioid use
      disorders were more likely to suffer pulmonary complications, with a frequency of
      4.2% compared to 1.6% in the nonopioid-dependent group (P < .001), and had a 1.62
      times higher odds (95% confidence interval [CI], 1.16-2.27) in multivariable
      regression analysis. In a secondary subgroup analysis, only patients undergoing a
      colectomy had a greater odds of suffering pulmonary complications (odds ratio,
      2.64; 95% CI, 1.42-4.91; P = .0021). Additionally, patients with an opioid use
      disorder had a longer length of stay (0.84 days [95% CI, 0.52-1.16; P < .001])
      and greater costs ($1816 [95% CI, 935-2698; P < .001]). CONCLUSIONS: This study
      demonstrates that patients with opioid use disorders are at increased risk for
      postoperative pulmonary complications, and have prolonged length of stay and
      resource utilization. Further research is needed regarding interventions to
      reduce the risk of complications in this subset of patients.

PMID- 29570153
TI  - Neural Invasion Spreads Macrophage-Related Allodynia via Neural Root in
      Pancreatic Cancer.
AB  - BACKGROUND: Neural invasion (N-inv) induces the neural damage and pain in
      pancreatic cancer (PCa). Benign nerve injury evokes allodynia through
      neuroinflammation in the neural root, which might be seen in PCa. Macrophages
      have the potential to release excitatory cytokines after nerve injury and so may
      play a role in the generation of chronic neuropathic pain. The aim of this study
      is to represent N-inv-induced allodynia in patients with PCa and to characterize
      allodynia-related neuroinflammation as macrophage accumulation on dorsal root
      ganglion (DRG) in the N-inv animal model (N-inv model). METHODS: Treatment-naive
      patients with advanced PCa with no opioid use were enrolled in the clinical
      study. To evaluate allodynia, the current perception threshold on epigastric skin
      and pain score from questionnaire were measured. The association between the
      degrees of radiological N-inv and allodynia was evaluated. In the animal
      experiments, we used the N-inv model, which is established by the inoculation of
      the human PCa cell line into the left sciatic nerve of mice and mimics the
      invasion behavior of human PCa. The change of sensation was weekly measured at
      right hind paw, and the expressions of mRNA and protein were investigated on DRG
      at 6 weeks in the N-inv and sham models. The effect of macrophage depletion using
      liposome-encapsulated clodronate (Lp-CLD) was evaluated in the N-inv model. Tumor
      size and the degree of macrophage accumulation on DRG or around the tumor were
      investigated. RESULTS: In the clinical study, 43 patients were analyzed. The
      threshold of epigastric skin at 2000 Hz touch and pressure sensation was
      decreased in patients with severe N-inv, compared to patients without severe N
      inv. Patients with severe N-inv showed a high pain score. In the animal
      experiments, the N-inv model decreased the threshold of right hind paw at 5 and 6
      weeks. The macrophage-related gene expression and F4/80-positive macrophages were
      increased in the left DRG. Lp-CLD-induced macrophage depletion induced an
      increase of the threshold in the right hind paw and a decrease of CD206-positive
      macrophages accumulation in the left DRG. Lp-CLD had no effect for tumor size.
      CONCLUSIONS: The present study first showed that the N-inv-induced allodynia was
      spread in patients with PCa and in the N-inv model. Allodynia was related to the
      amount of macrophages at DRG in the N-inv model. The neuroinflammation may be a
      target for researching the N-inv-induced pain mechanism and developing novel
      analgesics.

PMID- 29570155
TI  - Transition to College and Adherence to Prescribed Attention Deficit Hyperactivity
      Disorder Medication: Erratum.

PMID- 29570154
TI  - Isoflurane Impacts Murine Melanoma Growth in a Sex-Specific, Immune-Dependent
      Manner: A Brief Report.
AB  - The impact of volatile anesthetics on cancer progression has been observed for
      decades, but sex differences have not been described. Male and female immune
      systems vary considerably, and the immune system plays an important role in
      limiting cancer growth. Currently, mouse models describing the impact of volatile
      anesthetics on cancer growth are limited to same-sex models. In this brief
      report, we describe a sex-specific impact of isoflurane on melanoma growth
      observed in wild-type but not in immune-deficient mice. Future experimental
      designs related to anesthesia and cancer should evaluate the biological variable
      of sex in a systematic manner.

PMID- 29570156
TI  - ADHD Medication Adherence in College Students-A Call to Action for Clinicians and
      Researchers: Commentary on 'Transition to College and Adherence to Prescribed
      Attention Deficit Hyperactivity Disorder Medication': Erratum.

PMID- 29570157
TI  - Femoral head wedge resection for the treatment of avascular necrosis of the
      femoral head after pediatric femoral neck fracture: a case report.
AB  - This research focuses on femoral head wedge resection for the treatment of
      avascular necrosis (AVN) of the femoral head. A 9-year-old girl presented to the
      emergency room complaining of right hip pain that occurred after a pedestrian car
      accident. After 8 months of internal fixation using cannulated screws for Delbet
      type 2 fracture of the femoral neck, AVN of the femoral head developed in the
      patient. Even though valgus-derotation-extension intertrochanteric osteotomy was
      performed for the treatment of AVN, it progressed further and femoral head wedge
      resection was performed to recover the femoral head sphericity. After 3 years of
      follow-up, radiograph results showed appropriate and satisfactory congruency and
      containment. This research shows that the treatment of AVN of the femoral head
      using femoral head wedge resection is an effective method that can yield
      excellent results.

PMID- 29570158
TI  - Growth hormone promotes neurite growth of spiral ganglion neurons.
AB  - Intact spiral ganglion neurons are a specific requirement for hearing
      rehabilitation in deaf patients by cochlear implantation. Neurotrophic growth
      factors have been proposed as effective tools to protect and regenerate spiral
      ganglion neurons that are degenerated in the majority of patients suffering from
      hearing loss. Here, we show that growth hormone (GH), a pleiotropic growth factor
      whose neurotrophic role in the inner ear is still unclear, significantly
      increases neurite extension, as well as neuronal branching, in spiral ganglion
      cell cultures derived from early postnatal rats. Our data suggest that GH can act
      as a potent neurotrophic factor for inner ear neurons, which specifically
      promotes neurite growth. These effects might be elicited in a direct way or,
      alternatively, by induction of other growth factors that account for the observed
      neurotrophic effects. Thus, we conlude that GH might represent a novel candidate
      for the treatment of neurodegeneration in the hearing-impaired inner ear that has
      the potential to ultimately improve the performance and outcome of modern
      auditory implants.

PMID- 29570159
TI  - Generation of human vascularized brain organoids.
AB  - The aim of this study was to vascularize brain organoids with a patient's own
      endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis
      patient were grown into whole-brain organoids. Simultaneously, iPSCs from the
      same patient were differentiated into ECs. On day 34, the organoid was re
      embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro
      for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals
      were perfused on day 68. Coating of brain organoids on day 34 with ECs led to
      robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in
      vivo. Human CD31-positive blood vessels were found inside and in-between rosettes
      within the center of the organoid after transplantation. Vascularization of brain
      organoids with a patient's own iPSC-derived ECs is technically feasible.

PMID- 29570161
TI  - Authors' Response.

PMID- 29570160
TI  - Descriptive Profile of Lumbopelvic Control in Collegiate Baseball Pitchers.
AB  - Laudner, K, Wong, R, Latal, J, and Meister, K. Descriptive profile of lumbopelvic
      control in collegiate baseball pitchers. J Strength Cond Res 32(4): 1150-1154,
      2018-Throwing a baseball requires the transmission of forces generated in the
      lower extremity, through the trunk, then to the upper extremity, and ultimately
      out through the ball. Disruptions in this kinetic chain, specifically in
      lumbopelvic control, have been associated with decreased pitching performance and
      increased risk of injury. The purpose of this study was to establish normative
      data of lumbopelvic control among collegiate baseball pitchers. Data were
      compared bilaterally and with a group of nonthrowing physically active
      individuals. Eighteen asymptomatic pitchers and 30 nonthrowing subjects
      participated in this study. Each subject performed 6 separate tests bilaterally:
      single-leg balance, single-leg mini-squat, and static single-leg bridge. An iPod
      based tilt sensor was placed around the waist of each subject and used to
      determine the amount of anterior-posterior lumbopelvic tilt during each test.
      Independent t tests showed that neither group had any bilateral differences in
      lumbopelvic control (p > 0.10). The groups had similar lumbopelvic tilt values
      during the single-leg balance (p > 0.08) and mini-squat tests (p > 0.72), but a
      significant difference during the bridge maneuver. For this test, the pitchers
      had less lumbopelvic control than the control group for both the lead leg (p =
      0.003) and trail leg (p = 0.01). The descriptive values of this study may assist
      in designing lumbopelvic conditioning programs with the intent of enhancing
      pitching performance, as well as in the prevention, evaluation, and treatment of
      various injuries associated with lumbopelvic control deviations.

PMID- 29570162
TI  - IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer
      Cell M2 Polarization.
AB  - BACKGROUND: Recent studies have demonstrated that IL-34 is implicated in the
      regulation of macrophage functions. However, the effect of IL-34 on Kupffer cells
      (KCs) in acute rejection (AR) of liver transplantation remains unclear. METHODS:
      IL-34 expression was detected in graft and serum from allotransplantation and
      syngeneic transplantation groups. The adeno-associated virus-expressing IL-34 was
      used to assess the effect of IL-34 on AR of rat liver transplantation. The effect
      of IL-34 on KC polarization was evaluated by in vitro and in vivo assays. Kupffer
      cells in donors were depleted by clodronate treatment before transplantation, and
      the nontreated KCs or lipopolysaccharide-treated KCs were transferred into
      recipients during liver transplantation. RESULTS: IL-34 expression levels in
      grafts and serum were decreased in the allotransplantation group compared with
      the syngeneic transplantation group. Adeno-associated virus-expressing IL-34
      treatment induced KC M2 polarization in vivo and inhibited the AR of rat liver
      transplantation. Moreover, we found that IL-34 switched the phenotype of KCs from
      M1 to M2 by activating the PI3K/Akt pathway in vitro. In addition, the results of
      KC deletion and adaptive transfer experiments showed that the AR inhibition
      induced by IL-34 was M2 KC-dependent. CONCLUSIONS: IL-34 plays an important role
      in KC M2 polarization-dependent AR inhibition of rat liver transplantation.

PMID- 29570163
TI  - Conversion to Belatacept in Maintenance Kidney Transplant Patients: A
      Retrospective Multicenter European Study.
AB  - BACKGROUND: The use of belatacept is not yet approved for maintenance in kidney
      transplant patients. This retrospective multicenter European study aimed to
      assess the efficacy and safety of conversion to belatacept in a large cohort of
      patients in a real-life setting and to identify the predictive factors for
      improved kidney function after the switch. METHODS: Two hundred nineteen
      maintenance kidney transplant patients from 5 European kidney transplant centers
      were converted to belatacept at 21.2 months (0.1-337.1 months)
      posttransplantation, mainly because of impaired kidney function. Thirty-two
      patients were converted to belatacept within the first 3 months
      posttransplantation. The mean duration of follow-up was 21.9 +/- 20.2 months.
      RESULTS: The actuarial rate of patients still on belatacept-based therapy was
      77.6%. Mean estimated glomerular filtration rate increased from 32 +/- 16.4 at
      baseline to 38 +/- 20 mL/min per 1.73 m (P < 0.0001) at last follow-up.
      Conversion to belatacept before 3 months posttransplantation was the main
      predictive factor for a significant increase in estimated glomerular filtration
      rate (of 5 and 10 mL/min per 1.73 m at 3 and 12 months after the switch,
      respectively). Eighteen patients (8.2%) presented with an acute rejection episode
      after conversion; 3 developed a donor-specific antibody. Overall efficacy and
      safety were good, including for the 35 patients that had a donor-specific
      antibody at conversion. CONCLUSIONS: The conversion to belatacept was effective,
      especially when performed early after transplantation.

PMID- 29570164
TI  - The Benefits of Hypothermic Machine Preservation and Short Cold Ischemia Times in
      Deceased Donor Kidneys.
AB  - BACKGROUND: Hypothermic machine perfusion (HMP) of deceased donor kidneys is
      associated with better outcome when compared to static cold storage (CS).
      Nevertheless, there is little evidence whether kidneys with short cold ischemia
      time (CIT) also benefit from HMP and whether HMP can safely extend CIT. METHODS:
      We analyzed prospectively collected data from the Machine Preservation Trial, an
      international randomized controlled trial. Seven hundred fifty-two consecutive
      renal transplants were included: 1 kidney of each of the 376 donors was preserved
      by HMP, the contralateral organ was preserved by CS. RESULTS: The mean CIT was
      3:05 PM (SD, 4:58 AM). A subgroup analysis was performed, groups were based on
      CIT duration: 0 to 10 hours, 10 to 15 hours, 15 to 20 hours, or 20 hours or
      longer. Delayed graft function (DGF) incidence in the subgroup with up to 10
      hours CIT was 6.0% (N = 3/50) in the HMP arm and 28.1% (N = 18/64) in the CS arm
      (univariable P = 0.002; multivariable odds ratio [OR], 0.02; P = 0.007). Cold
      ischemia time remained an independent risk factor for DGF for machine perfused
      kidneys recovered from donation after brain death donors (OR, 1.06; 95%
      confidence interval [CI], 1.017-1.117; P = 0.008), donation after circulatory
      death donors (OR, 1.13; 95% CI, 1.035-1.233; P = 0.006) and expanded criteria
      donors (OR, 1.14; 95% CI, 1.057-1.236; P = 0.001). CONCLUSIONS: In conclusion,
      HMP resulted in remarkably lower rates of DGF in renal grafts that were
      transplanted after a short CIT. Also, CIT remained an independent risk factor for
      DGF in HMP-preserved kidneys.

PMID- 29570165
TI  - Minimizing Risk Associated With Older Liver Donors by Matching to Preferred
      Recipients: A National Registry and Validation Study.
AB  - BACKGROUND: Allografts from older liver donors (OLDs), 70 years or older are
      often discarded for fear of inferior outcomes. We previously identified
      "preferred recipients" who did not suffer the higher risk of graft loss and
      mortality associated with OLDs. Preferred recipients were first-time, non-status
      1 registrants older than 45 years, body mass index less than 35, indication other
      than hepatitis C, and cold ischemia time less than 8 hours. METHODS: We assessed
      the validity of the preferred recipient construct in a larger, more recent cohort
      (38 891 patients, 2006-2013). We compared recipients of OLD grafts to recipients
      of average liver donors (ALDs, age = 40-69) and ideal liver donors (ILDs, age =
      18-39) grafts using multilevel Cox regression adjusting for recipient and
      transplant factors. RESULTS: The use of OLD grafts in preferred recipients has
      increased from 2006 to 2013 (P = 0.02). Preferred recipients Model for End-Stage
      Liver Disease scores ranged 6 to 40. Preferred recipients had similar 5-year all
      cause graft loss (ACGL) with OLD versus ALD and ILD grafts (25.4% vs 24.5% and
      21.6%). Conversely, nonpreferred recipients had higher 5-year ACGL with OLD
      versus ALD and ILD grafts (41.4% vs 32.9% and 25.6%). After adjustment, preferred
      recipients had similar graft loss with OLD versus ALD grafts (hazard ratio [HR],
      0.921.081.27; P = 0.3) and ILD grafts (HR, 0.981.161.39, P = 0.09); however,
      nonpreferred recipients had higher ACGL risk with OLD grafts versus ALD (HR,
      1.281.411.56, P < 0.001) and ILD grafts (HR, 1.501.671.86, P < 0.001). Similar
      trends are seen with mortality. CONCLUSIONS: Because preferred recipients
      comprise 43.3% (n = 2916) of the current waitlist and span the full range of
      Model for End-Stage Liver Disease scores, transplanted OLD allografts could be
      distributed without added risk of graft loss or mortality.

PMID- 29570166
TI  - The Authors' Reply.

PMID- 29570168
TI  - New Insights on the Role of Kupffer Cells in Liver Transplantation.

PMID- 29570167
TI  - Advanced Morphologic Analysis for Diagnosing Allograft Rejection: The Case of
      Cardiac Transplant Rejection.
AB  - Allograft rejection remains a significant concern after all solid organ
      transplants. Although qualitative morphologic analysis with histologic grading of
      biopsy samples is the main tool employed for diagnosing allograft rejection, this
      standard has significant limitations in precision and accuracy that affect
      patient care. The use of endomyocardial biopsy to diagnose cardiac allograft
      rejection illustrates the significant shortcomings of current approaches for
      diagnosing allograft rejection. Despite disappointing interobserver variability,
      concerns about discordance with clinical trajectories, attempts at revising the
      histologic criteria and efforts to establish new diagnostic tools with imaging
      and gene expression profiling, no method has yet supplanted endomyocardial biopsy
      as the diagnostic gold standard. In this context, automated approaches to complex
      data analysis problems-often referred to as "machine learning"-represent
      promising strategies to improve overall diagnostic accuracy. By focusing on
      cardiac allograft rejection, where tissue sampling is relatively frequent, this
      review highlights the limitations of the current approach to diagnosing allograft
      rejection, introduces the basic methodology behind machine learning and automated
      image feature detection, and highlights the initial successes of these approaches
      within cardiovascular medicine.

PMID- 29570169
TI  - Telomerase reverse transcriptase promoter mutations and solar elastosis in
      cutaneous melanoma.
AB  - The aims of this study were to assess the prognostic potential of solar elastosis
      grading and telomerase reverse transcriptase (TERT) promoter mutations (TERTp) in
      melanoma and to evaluate whether an association between solar elastosis and TERTp
      exists. Solar elastosis in the dermis was evaluated in hematoxylin and eosin
      stained whole slides from 486 malignant melanomas. Pyrosequencing was used to
      detect TERTp in 189 samples. There was no association between solar elastosis and
      TERTp (P=0.3). Severe elastosis was associated with older age (P<0.0001),
      ulceration (P=0.03), and location in the head/neck region (P<0.0001). The absence
      of elastosis was associated with younger age (P<0.0001), benign nevus remnants
      (P=0.001), and a positive BRAF V600E expression (P<0.0001). Severe elastosis
      predicted a worse relapse-free survival (hazard ratio: 2.18; 95% confidence
      interval: 1.30-3.64; P=0.003). However, it was not independent of age. TERTp was
      not associated with any adverse prognostic or clinicopathological outcome, nor
      any mitogen-activated protein kinase-related protein expressions. However, at a
      cutoff corresponding to the sensitivity of Sanger sequencing, TERTp predicted
      melanoma-specific death independently of age, and was associated with Breslow
      thickness, ulceration, tumor stage at diagnosis, BRAF V600E oncoprotein, and
      absence of p16 expression. In conclusion, TERTp were not related to severe
      elastosis and may thus be triggered by both chronic and acute intermittent sun
      exposure, the latter not visible on ordinary hematoxylin and eosin-stained
      slides. Neither TERTp nor severe elastosis predicted an adverse outcome in
      melanoma. An absence of elastosis was seen in younger melanoma patients and may
      be used to select those melanomas originating in a nevus, which often harbors a
      BRAF mutation.

PMID- 29570170
TI  - Fatty acid receptor GPR120: a novel marker for human melanoma.
AB  - The correlation between ultraviolet radiation of the skin and melanoma incidence
      in humans is well established. Interestingly, epidemiologic data suggest also a
      correlation to an increased BMI pointing to metabolic trigger factors in melanoma
      pathogenesis. To substantiate this connection, we studied the expression of G
      protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long
      chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections
      histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma
      metastasis (n=43) were immunohistochemically stained against GPR120. The staining
      was evaluated by three trained dermatopathologists and independently scored.
      Compared with nevi, primary melanoma and melanoma metastasis showed significantly
      higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120
      expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0-10],
      whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS
      score: 7, range: 0-12) and in melanoma metastasis 27 out of 43 were highly GPR120
      positive (median IRS score: 9, range: 0-12). GPR120 expression and tumor
      thickness (mm) show a statistically significant correlation in primary melanoma
      (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis
      and in sebaceous and sweat glands, which is yet not described. This study
      identified GPR120 as a novel marker for melanoma, indicating that melanoma cells
      are sensitive to free fatty acids. It is tempting to speculate that
      pharmacologically interfering with GPR120 signaling might improve melanoma
      therapy.

PMID- 29570171
TI  - Factors Associated With Health Care Utilization of Recurrent Clostridium
      difficile Infection in New York State.
AB  - BACKGROUND: The incidence of infection due to Clostridium difficile infection
      (CDI) and subsequent economic burden are substantial. GOALS: The impact of
      changing practice patterns on demographics at risk and utilization of health care
      resources for recurrence of CDI remains unclear. STUDY: A total of 291,163
      patients hospitalized for CDI were identified from 1995 to 2014 from the New York
      SPARCS database. The chi test, the Welch t test, and multivariable logistic
      regression analysis were performed to evaluate factors related to readmission.
      RESULTS: Hospital admissions and readmissions for CDI peaked in 2008 at 20,487
      and 13,795, respectively, and have since decreased (linear trend, 0.9706 and
      0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required >=2
      admissions. Risk factors for readmission included: age 55 to 74, government
      insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary
      disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and
      depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165
      and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830
      (0.63%) patients with CDI underwent surgery, with emergent being more common than
      elective (71% vs. 29%). CONCLUSIONS: Hospital admissions and readmissions for CDI
      peaked in 2008 and have since been steadily declining. These trends may be
      secondary to improved diagnostic capabilities and evolving antibiotic regimens.
      More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk
      factors for these patients have been identified. Although <1% of all patients
      with CDI undergo surgery, these rates have also been declining.

PMID- 29570173
TI  - Gastric Emptying of Elemental Liquid Diets Versus Semisolid Diets in Bedridden
      Gastrostomy-fed Patients.
AB  - BACKGROUND: Aspiration is a common problem in bedridden gastrostomy-fed patients.
      We compared gastric emptying of an elemental liquid diet and a commercial
      semisolid diet in bedridden gastrostomy-fed patients. METHODS: Study 1: from
      January 2013 to December 2016, consecutive bedridden patients receiving
      percutaneous endoscopic gastrostomy (PEG) semisolid feeding hospitalized due to
      aspiration pneumonia were switched to elemental liquid diet feedings. The
      frequency of defecation, tube feed contents aspirated from the trachea, and
      aspiration pneumonia during hospitalization were retrospectively reviewed. Study
      2 was a randomized, crossover trial comparing C sodium acetate gastric emptying
      of a commercial elemental liquid or a commercial semisolid diet in bedridden PEG
      patients and controls. RESULTS: Study 1: 18 patients were enrolled. Elemental
      liquid diet was aspirated from the trachea in 1 (5.6%) (once in 24 observations);
      neither aspiration pneumonia nor diarrhea developed during elemental liquid diet
      feeding over 2 weeks observation. Study 2: 8 PEG patients and 8 healthy subjects
      were separately randomized to assess gastric emptying of the commercial elemental
      and semisolid diets. The elemental liquid diet was associated with a significant
      decrease of the 10%, 30%, or 50% emptying (excretion) time (P<0.05) and an
      increased the area under the curve (% dose/h) compared with the commercial
      semisolid diet (P<0.05). In healthy subjects there was no significant difference
      in gastric empting between the 2 diets. CONCLUSIONS: Elemental liquid diets
      emptied more rapidly from the stomach than semisolid diets in bedridden PEG
      patients. They may prevent or reduce aspiration pneumonia compared with semisolid
      diets.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- 29570172
TI  - Sessile Serrated Adenomas in Young Patients may have Limited Risk of Malignant
      Progression.
AB  - GOALS: To provide preliminary evidence that sessile serrated adenomas (SSA) are
      low-risk polyps in young patients. BACKGROUND: SSAs are the dominant polyp of the
      serrated neoplasia pathway and as such are the precursor of up to 20% of
      colorectal carcinomas (CRC). Up to 90% of these cancers are expected to harbor a
      BRAF mutation. SSAs are being diagnosed with increasing frequency in young
      patients, placing a significant burden on colonoscopic services. Evidence to
      direct the surveillance intervals for these young patients is not available.
      STUDY: We utilized 2 patient cohorts comprising (1) a consecutive series of
      patients who underwent outpatient colonoscopy through a tertiary hospital and (2)
      a consecutive series of resection specimens for CRC processed through a
      gastrointestinal pathology service. The prevalence of SSAs by age was determined
      in the patients undergoing colonoscopy and compared with the ages of patients
      with BRAF mutated CRC in the pathology series. RESULTS: The prevalence of SSAs
      was similar irrespective of age. By comparison, BRAF mutated CRCs were very rare
      (3.8% of cases) in patients younger than 50 years of age and uncommon (9.3% of
      cases) in patients younger than 60 years of age, but increased to 39.8% in
      patients older than 80 years of age. CONCLUSIONS: These results suggest that SSAs
      develop at a young age, but have a prolonged dwell time and are unlikely to
      develop into cancer in patients younger than 60 years of age. These findings
      highlight the need for further targeted research to determine the most
      appropriate surveillance intervals for young patients with sporadic SSAs.

PMID- 29570174
TI  - Spontaneous Pneumothorax in a Young Child With Pulmonary Tuberculosis.
AB  - We report a 2-year-old, previously healthy boy, who presented with chronic
      pneumonia. He was diagnosed with culture-confirmed pulmonary tuberculosis.
      Complications included spontaneous pneumothorax presumed to be secondary to
      cavity formation and complete subsegmental airway obstruction that did not
      resolve with prolonged oral corticosteroid treatment.

PMID- 29570175
TI  - Optimizing Accessibility of a Hand-Wash Gel to Infant's Cradle: Effect on
      Neonatal Conjunctivitis.
AB  - BACKGROUND: In our recent study in 2015, we showed a significant relationship
      between increased rate of clinical neonatal conjunctivitis (CNC) and performance
      of eye red reflex (RR) examination. Our study aim was to assess whether improved
      accessibility of staff to disinfectant gel (via attaching the gel bottle to
      infant's cradle) will increase the caring staff compliance with hand hygiene and
      decrease the rate of CNC. METHODS: Our intervention included attaching bottles of
      alcohol-based gel to newborns' cradles to insure full availability and
      accessibility of hand-wash disinfectant. We included all newborn infants who were
      born beyond 35 weeks' gestation and stayed in the well-baby nursery. We compared
      two periods: pre-intervention period (n=9380) vs. an intervention period
      (n=8087). Three variables were recorded: (a) rate of CNC: number of conjunctival
      swabs sampled /1000 newborns whenever an eye discharge was noted, (b) rate of
      bacterial conjunctivitis: number of positive swabs/1000 newborns, (c) percentage
      of positive swabs out of all sampled swabs. RESULTS: Compared to pre-intervention
      period, the rate of CNC dropped significantly during the intervention period:
      28.6/1,000 vs. 21.3/1,000, respectively, p<0.01. However, the number of positive
      bacterial swabs/1000 newborns (3.2 vs. 2.5) and the percentage of positive
      bacterial swabs of all sent samples (11.6% vs. 10.8%) were not different between
      the two periods. The majority of pathogens in swabs were gram-negative sp.
      without difference between study periods (77.4% versus 80%), respectively.
      Univariate analysis showed significant association between rate of CNC and longer
      length of stay> 5days (p<0.001) and vaginal delivery (VD). Logistic stepwise
      regression analysis showed that 4 variables were significantly and independently
      associated with higher rate of clinical conjunctivitis. These include birth
      during pre-intervention period (p=0.018, OR 1.27, 95% CI 1.04-1.54), length of
      stay 4-5 days (p<0.001, OR 2.23 CI 1.63-3.06), length of stay > 7 days (p<0.001,
      OR 6.51 CI 4.24-10.02), vaginal delivery (p=0.004, OR 1.6 CI 1.17-2.2) and male
      gender (p=0.006, OR 1.31 CI 1.08-1.59). CONCLUSIONS: Accessibility of a
      disinfectant gel within each newborn's cradle raised hygiene awareness among the
      caring staff and contributed to reduction of CNC rate in the newborn nursery.

PMID- 29570176
TI  - A Rare Complication of Giardiasis in Children: Protein Losing Enteropathy.
AB  - Protein-losing enteropathy (PLE) may develop as a complication of a wide spectrum
      of diseases. Three cases of giardiasis that presented with acute onset of
      hypoalbuminemia were documented, and resolution of protein loss after treatment
      was also confirmed. Thus, chronic enteric infections should be considered as an
      etiology of severe intestinal protein loss, particularly in children.

PMID- 29570177
TI  - Multifocal Skin Tuberculosis: Report of A Case.
AB  - Tuberculosis (TB) is a severe problem in underdeveloped countries. Cutaneous TB
      is rare and often goes unrecognized. We report a Pakistani child with multifocal
      cutaneous and pulmonary TB. Microbiologic diagnosis was obtained when the
      abscesses were biopsied. Four-drug therapy produced rapid improvement of the
      lesions. A high level of suspicion must be maintained when evaluating children
      from countries at risk.

PMID- 29570178
TI  - Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in
      Kawasaki Disease.
AB  - BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart
      disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a
      known risk factor for cardiac sequelae. Previously reported risk factors for
      nonresponse include age, male sex and laboratory abnormalities. We set out to
      identify additional risk factors for IVIG nonresponse in a racially diverse KD
      population. METHODS: We conducted a retrospective chart review at a referral
      center in the Southeastern United States of children meeting ICD-9 (International
      Statistical Classification of Disease and Related Health Problems) criteria for
      KD and being treated with IVIG. RESULTS: Four-hundred and fifty-nine children met
      inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis,
      unknown race, or failure to meet the American Heart Association guideline
      criteria. Our final cohort consisted of 392 subjects, with median age of 2.7
      years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a
      single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4%
      developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more
      likely to be Black, have higher white blood cell, erythrocyte sedimentation rate
      and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require
      critical care and hospital readmission. Responders achieved echocardiographic
      normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002)
      and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year.
      Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02).
      CONCLUSIONS: Nonresponders have higher rates and greater severity of coronary
      involvement than responders. Our study uniquely demonstrates Black race as a risk
      factor for nonresponse and for delayed normalization of cardiac involvement at 1
      year follow-up.

PMID- 29570179
TI  - Breakthrough Candidemia In Children On Micafungin.
AB  - We identified 8 pediatric patients on micafungin (MCFG; >=3 doses) at our
      institution who had breakthrough candidemia (BC). The causative strains of the BC
      were Candida parapsilosis in 7 patients. The minimum inhibitory concentration of
      MCFG was <=1 ug/mL (susceptible) in all 8 isolates. Immunocompromised patients
      may develop BC caused by MCFG-susceptible strains.

PMID- 29570180
TI  - Re-creation of Horsepox Virus.

PMID- 29570181
TI  - [Benign liver tumours - current diagnostics and therapeutic modalities].
AB  - The most common benign liver tumours are haemangiomas, focal nodular hyperplasia
      and hepatocellular adenoma. We perform a review of the literature and show the
      current diagnostic and therapeutic modalities based on the EASL Clinical Practice
      Guideline. With the widespread use of ultrasound, the detection of liver lesions
      is increased. They are usually found in women of childbearing age with atypical
      abdominal pain or incidentally. Contrast-enhanced US, CT or MRI are usually
      necessary for differential diagnosis. In atypical appearance or in malignancy
      suspect cases biopsy could be performed. For symptomatic patients conservative
      therapy can be sufficient. In haemorrhagic cases transarterial embolisation can
      be useful, also for tumour size decreasing before surgery. In patients with
      persisting symptoms, with vessel or soft tissue compression effect or in
      malignancy suspect cases definitive surgical treatment is advised. In men with
      hepatocellular adenoma primary resection is appropriate because of the higher
      risk for malignant transformation. As alternative treatment options
      radiofrequency ablation, irradiation, chemotherapy, monoclonal antibody therapy
      or liver transplantation are published.

PMID- 29570182
TI  - [Surgical treatment of primary liver malignancies].
AB  - The incidence of primary malignant liver tumours is globally rising.
      Hepatocellular carcinoma constitutes 75-85% of primary liver malignancies. Owing
      to advancements of oncological therapies, several methods are available to combat
      the tumour. Upon the complexity of the disease and the wide spectrum of
      therapeutical regimens, therapy of HCC is debated, with several undecided issues.
      Noteworthy, however, is that in early tumour stages, as a de facto curative
      approach, surgical therapy remains the most effective, allowing long-term
      survival. Intrahepatic cholangiocellular carcinoma (iCCC) is the second most
      frequent primary malignant liver tumour. Despite technical developments,
      prognosis of iCCC patients remains dismal. Unfortunately, as the sole curative
      approach, surgery (nearing 40% 5-year survival) is mostly contraindicated because
      of a late diagnosis. In these cases, median survival remains below 7-12 months
      despite parallel palliative therapies. The present review focuses on the surgical
      management of primary malignant liver tumours.

PMID- 29570183
TI  - [Liver transplantation in the treatment of hepatic tumors].
AB  - The indications for liver transplantation have become generally accepted over the
      last decades. However, in the last ten years, this indication area changes, it
      seems to be enlarged. Increasingly, previously classified as contraindications
      have become indications like cholangiocarcinoma or colorectal cancer liver
      metastases in selected cases. We have reviewed the old and new oncologic
      indications, whose survival rates do not differ from liver transplants due to
      other indications.

PMID- 29570184
TI  - [Surgical treatment of secondary liver malignancies].
AB  - Surgical treatment of liver metastases, under certain conditions, can be a step
      of a multidisciplinary treatment strategy for advanced malignant disease.
      Nevertheless, it is not the same if metachronous or synchronous metastases are
      planned to be treated. Indications for surgery are the most clearly defined and
      accepted in cases of colorectal and neuroendocrine liver metastases. At the same
      time, the steps of the traditional oncotherapy has changed in the management of
      synchronous colorectal metastases: the novel concept of the treatment strategy is
      removing the liver metastases before the colorectal primary. The role of surgery
      is less clear and defined in the management of metastases from other, non
      colorectal and non-neuroendocrine primaries. The main purpose is to evaluate
      which kind of criteria should be fulfilled to indicate the resection of liver
      metastases, which are the conditions that, when present, may provide a benefit to
      a patient from surgery, improving survival. These criteria have not been
      clarified precisely yet; randomized prospective trials are needed. Consensus
      recommendations in such cases could be determined based on the results of the
      mentioned trials.

PMID- 29570185
TI  - [Laparoscopy in liver surgery].
AB  - More than 9000 laparoscopic liver resections (LLR) are performed worldwide for
      benign lesions, malignancy (mainly for hepatocellular carcinoma and colorectal
      cancer liver metastasis), and living donor hepatectomy. Although there is no
      absolute size criterion, smaller, peripheral lesions (<5 cm) of the
      anteriolateral segments, that lie far from major vessels and anticipated
      transection planes are most amenable to LLR, but nowadays lesions of the less
      ideal posterosuperior segments are feasible for LLR too. Centers with extensive
      experience in hepatobiliary surgery and laparoscopy have performed laparoscopic
      major hepatic resections with satisfactory outcomes. Patient benefits from LLR
      include less intraoperative blood loss, less postoperative pain and painkiller
      requirement, early mobilization and shorter length of hospital stay, with
      comparable postoperative morbidity and mortality to open liver resection.
      Comparison studies between open resection and LLR have revealed no differences in
      width of resection margins or overall survival after resection for hepatocellular
      cancer or colorectal cancer liver metastases. Other advantages of LLR for HCC are
      avoidance of collateral vessel ligation, decreased postoperative hepatic
      insufficiency and fewer postoperative adhesions, all of them facilitates a
      possible subsequent liver transplantation.

PMID- 29570186
TI  - [Role of interventional radiological procedures in the treatment of liver
      cancer].
AB  - Invasive radiological procedures provide more and more therapeutic options for
      patients with liver cancer. The treatment options previously used as a 2nd/3rd
      line treatment are making their way to 1st line treatment in selected cases. In
      this review, the authors take an overview of the interventional radiological
      procedures used in the most frequent liver neoplasms. There is a rapid
      development in ablational therapy, especially in the volumetric planning and
      stereotactic navigation. Using those new devices, the reliability of the ablation
      can improve a lot. At the field of embolization, new randomized studies were
      published recently, which can help to choose the right patient group who gains
      the most from the treatment. Interventional radiology has now an established
      place in the team of specialists treating malignant liver diseases.

PMID- 29570187
TI  - [Systemic treatment options of primary hepatocellular carcinoma].
AB  - Hepatocellular carcinoma is the most common primary malignancy of the liver, with
      increasing incidence worldwide. Chronic liver diseases, especially liver
      cirrhosis, are the primary risk factors in the pathogenesis. Curative therapy is
      usually possible only in early disease, however, most cases are diagnosed at
      advanced stage. Until recently sorafenib was the only viable option for systemic
      treatment, however, over the past years many new targeted and immunotherapy drugs
      proved to be efficient in first and second line as well.

PMID- 29570188
TI  - [Stereotactic body radiotherapy of liver metastasis: early experience].
AB  - Recently the prevalence of oligometastatic patients is increasing. A common site
      of distant spread is the liver. The standard of care is curative surgical
      resection, however, the resecability rate is only 10-20%. Alternatively,
      radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) may be
      used. Stereotactic ablative body radiotherapy (SABRT) makes it possible to
      deliver curative radiation dose without radiation injury to the healthy liver
      tissue. We delivered SABRT to three patients with inoperable hepatic metastases.
      The primary tumors were rectal (2) and lung (1). The dose was 3x20 Gy every other
      day. We observed one grade 1 side effect. All the metastases showed complete
      remission and no local recurrence or late side effect occurred during the one
      year of follow-up. One patient is tumor-free, one has stable disease, in one
      patient two new hepatic metastases appeared and receives chemo-biological
      therapy. SABRT of liver metastases is safe and highly effective. It can be
      expected that in the near future it will become one of the standard treatments of
      hepatic tumors.

PMID- 29570189
TI  - [Alcohol and breast cancer. A short survey].
AB  - Regular consumption of alcohol increases the risk of developing (one or more of)
      several malignant conditions: the frequency of tumours in the aerodigestive
      tract, in the liver, in the colorectal region and in the breast is increased. The
      principal carcinogen component of alcoholic drinks is ethanol itself; the effect
      is unmistakably proportional to the daily/weekly dosage. Under the influence of
      alcohol-dehydrogenase, ethanol will metabolise to acetaldehyde, which is a known
      carcinogen. Among other things chronic alcohol consumption promotes the
      production of endogen hormones, affects the insulin-like growth factor-1, alters
      several biological pathways, raises oxidative stress, and damages the genes. Even
      modest daily alcohol intake will increase the risk of breast cancer.

PMID- 29570190
TI  - Albumin as a "Trojan Horse" for polymeric nanoconjugate transendothelial
      transport across tumor vasculatures for improved cancer targeting.
AB  - Although polymeric nanoconjugates (NCs) hold great promise for the treatment of
      cancer patients, their clinical utility has been hindered by the lack of
      efficient delivery of therapeutics to targeted tumor sites. Here, we describe an
      albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium
      barrier through a caveolae-mediated transcytosis pathway to better target cancer.
      The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of
      poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains
      followed by subsequent surface decoration of albumin. The administration of Alb
      NCs into mice bearing MCF-7 human breast cancer xenografts with limited tumor
      vascular permeability resulted in markedly increased tumor accumulation and anti
      tumor efficacy compared to their conventional counterpart PEGylated NCs (PEG
      NCs). The Alb-NC provides a simple, low-cost and broadly applicable strategy to
      improve the cancer targeting efficiency and therapeutic effectiveness of
      polymeric nanomedicine.

PMID- 29570191
TI  - Design of iron atom modified thiophene-linked metalloporphyrin 2D conjugated
      microporous polymer as CO2 reduction photocatalyst.
AB  - Herein, by means of density functional theory (DFT) calculations, we designed a
      new type of thiophene-linked porphyrin unit and incorporated it into an extended
      2D conjugated microporous polymer (CMP) to serve as a CO2 reduction catalyst.
      This newly designed catalyst combines the advantages of molecular catalysis,
      heterogeneous catalysis, high structural stability and tunable electronic
      properties. A series of metal atoms (Fe, Mg, Mn, and Cu) were introduced into the
      center of the porphyrin ring to modify its capacity for reducing CO2. Our
      transition state (TS) search calculations revealed that the Fe-modified CMP
      possessed the highest catalytic activity toward CO2 reduction. The plausible
      reduction pathway was also determined. The band structure and frontier orbital
      distribution calculations further demonstrated its semimetallic property and
      higher stimulated transition probability, both of which are critical factors for
      photocatalytic performance. We hope that our design could provide meaningful
      guidance for other relevant CO2 catalytic reactions.

PMID- 29570192
TI  - Evidence of homo-FRET in quantum dot-dye heterostructured assembly.
AB  - With an aim to understand the intermolecular/particle interaction and the optical
      properties of the inorganic-organic hybrid nanostructured materials, Forster
      resonance energy transfer (FRET) between negatively charged CdS quantum dots
      (donor) and positively charged Oxazine 170 perchlorate (acceptor) has been
      investigated by employing steady-state and time-resolved fluorescence
      spectroscopy. Investigations revealed that size-dependent changes in the FRET
      efficiency of different QD-dye FRET pairs occurred mainly due to the
      electrostatic effects. Interestingly, the present study also reveals that at a
      higher concentration of dye molecules, aggregation occurs on the QD surface and
      the quenching of dye fluorescence occurs due to homo-FRET process. The homo-FRET
      process in this case has been established by exploiting steady-state fluorescence
      anisotropy measurements. The feasibility of aggregate formation and the homo-FRET
      interaction between the dye molecules has also been demonstrated through quantum
      mechanical calculations.

PMID- 29570194
TI  - Elucidating the amphiphilic character of graphene oxide.
AB  - The amphiphilic character of graphene oxide was analysed in terms of its
      interfacial activities, using atomistic molecular dynamics. Graphene oxides at
      four different degrees of oxygenation were investigated considering both the
      effects of oxidation and carboxyl edge-functionalization. Solvation free energies
      are strongly negative and of increasing magnitude with the concentration for all
      systems, even in the toluene phase, indicating that GO presents a favourable
      solvation in both pure liquids as well as interfaces. The PMF results indicate
      that only the R20 system is slightly active at the water/vacuum interface, with a
      PMF minimum of about -2.6 kJ mol-1. Both analyses, free energy and PMF, indicate
      that all systems with higher oxygen concentrations have lower free energy in
      water than in toluene, while the R20 system opposes this tendency. Comparison
      between the reduced GOs (20%) shows that edge-functionalised systems were more
      active than basal-functionalized systems, indicating that oxygen concentration
      plays a more relevant role than the distribution of functional groups.

PMID- 29570196
TI  - A quantitative and temporal map of proteostasis during heat shock in
      Saccharomyces cerevisiae.
AB  - Temperature fluctuation is a common environmental stress that elicits a molecular
      response in order to maintain intracellular protein levels. Here, for the first
      time, we report a comprehensive temporal and quantitative study of the proteome
      during a 240 minute heat stress, using label-free mass spectrometry. We report
      temporal expression changes of the hallmark heat stress proteins, including many
      molecular chaperones, tightly coupled to their protein clients. A notable lag of
      30 to 120 minutes was evident between transcriptome and proteome levels for
      differentially expressed genes. This targeted molecular response buffers the
      global proteome; fewer than 15% of proteins display significant abundance change.
      Additionally, a parallel study in a Hsp70 chaperone mutant (ssb1Delta)
      demonstrated a significantly attenuated response, at odds with the modest
      phenotypic effects that are observed on growth rate. We cast the global changes
      in temporal protein expression into protein interaction and functional networks,
      to afford a unique, time-resolved and quantitative description of the heat shock
      response in an important model organism.

PMID- 29570193
TI  - Phytol stimulates the browning of white adipocytes through the activation of AMP
      activated protein kinase (AMPK) alpha in mice fed high-fat diet.
AB  - Stimulating the browning of white adipocytes contributes to the restriction of
      obesity and related metabolic disorders. This study aimed to investigate the
      browning effects of phytol on mice inguinal subcutaneous white adipose tissue
      (iWAT) and explore the underlying mechanisms. Our results demonstrated that
      phytol administration decreased body weight gain and iWAT index, and stimulated
      the browning of mice iWAT, with the increased expression of brown adipocyte
      marker genes (UCP1, PRDM16, PGC1alpha, PDH, and Cyto C). In addition, phytol
      treatment activated the AMPKalpha signaling pathway in mice iWAT. In good
      agreement with the in vivo findings, the in vitro results showed that 100 MUM
      phytol stimulated brown adipogenic differentiation and formation of brown-like
      adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content
      and oxygen consumption, and promoting mRNA and/or protein expression of brown
      adipocyte markers (UCP1, PRDM16, PGC1alpha, PDH, Cyto C, Cidea and Elovl3) and
      beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the
      AMPKalpha signaling pathway in the differentiated 3T3-L1. However, the inhibition
      of AMPKalpha with Compound C totally abolished phytol-stimulated brown adipogenic
      differentiation and formation of brown-like adipocytes. In conclusion, these
      results showed that phytol stimulated the browning of mice iWAT, which was
      coincident with the increased formation of brown-like adipocytes in the
      differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKalpha
      signaling pathway. These data provided new insight into the role of phytol in
      regulating the browning of WAT and suggested the potential application of phytol
      as a nutritional intervention for the restriction of obesity and related
      metabolic disorders.

PMID- 29570195
TI  - DNA nanoclew templated spherical nucleic acids for siRNA delivery.
AB  - A superior biocompatible spherical nucleic acid (SNA) conjugate was fabricated by
      grafting siRNA onto the surface of a core composed of a spherical DNA
      nanostructure that we have termed a DNA nanoclew (DC). After uptake by cultured
      cancer cells, SNA nanoparticles release engrafted siRNAs by cleavage of the
      intracellular Dicer enzyme. Moreover, in vitro experiments reveal that such SNAs
      demonstrate potent gene knockdown at both mRNA and protein levels, while with
      negligible cytotoxicity.

PMID- 29570200
TI  - Microfluidic determination of lymphocyte vascular deformability: effects of
      intracellular complexity and early immune activation.
AB  - Despite the critical importance of mechanical (rheological + extrudability)
      deformability in the vascular flow of lymphocytes, it has been poorly
      investigated due to the limitations of existing technological tools.
      Microfluidics analysis of leukocyte deformability offers significant advantages
      in that it offers high throughput, large sample population and the ability to
      analyze a heterogeneous population. These advantages are in stark contrast to
      previous approaches that focused on single cell measurements. Importantly, the
      flow characteristics of microfluidic devices more closely model vascular
      deformability in that shear stress is applied forcing leukocyte passage through
      micropores of designed size. The modeling of vascular flow has been further
      enhanced by the development of a microfluidic ratchet device that introduced an
      oscillatory flow. As demonstrated in this study, the microfluidic ratchet device
      was able to separate human peripheral blood leukocyte subsets (i.e., monocytes
      and lymphocytes) based on differential deformability profiles. Furthermore,
      morphologically similar lymphocyte subsets (CD4, CD8 and NK) could also be
      separated. The subset separation was observed to be largely due to differences in
      their intracellular complexity (i.e., granule content) with granule-positive T
      lymphocytes and NK cells being less deformable than granule-negative lymphocytes.
      Moreover, upon immune activation, deformability of the de-granulated lymphocytes
      increased consequent to the decrease in cytoplasmic granularity/viscosity. This
      study for the first time demonstrates that leukocytes subsets have differential
      deformability profiles and that intracellular granularity/degranulation
      significantly impacts the lymphocytes' mechanical properties. These findings
      could be of clinical value as biomarkers of lymphocyte activation state and
      potential disease processes.

PMID- 29570202
TI  - Introducing Molecular Omics.

PMID- 29570201
TI  - Anisotropic and amphoteric characteristics of diverse carbenes.
AB  - Despite its key importance in carbene chemistry, the amphoteric (i.e., both
      nucleophilic and electrophilic) behavior of the divalent carbon atom (:C) in
      carbenes is not well understood. The electrostatic potential (EP) around :C is
      often incorrectly described by simple isotropic atomic charges (particularly, as
      in singlet CF2); therefore, it should be described by the multipole model, which
      can illustrate both negative and positive EPs, favoring the positively and
      negatively charged species that are often present around :C. This amphotericity
      is much stronger in the singlet state, which has more conspicuous anisotropic
      charge distribution than the triplet state; this is validated by the complexation
      structures of carbenes interacting with Na+, Cl-, H2O, and Ag+. From the study of
      diverse carbenes [including CH2, CLi2/CNa2, CBe2/CMg2, CF2/CCl2,
      C(BH2)2/C(AlH2)2, C(CH3)2/C(SiH3)2, C(NH2)2/C(PH2)2, cyclic systems of
      C(CH2)2/C(CH)2, C(BHCH)2, C(CH2CH)2/C(CHCH)2, and C(NHCH)2/C(NCH)2], we elucidate
      the relationships between the electron configurations, electron
      accepting/donating strengths of atoms attached to :C, pi conjugation, singlet
      triplet energy gaps, anisotropic hard wall radii, anisotropic electrostatic
      potentials, and amphotericities of carbenes, which are vital to carbene
      chemistry. The (sigma2, pi2 or sigmapi) electronic configuration associated with
      :C on the :CA2 plane (where A is an adjacent atom) in singlet and triplet
      carbenes largely governs the amphoteric behaviors along the :C tip and :C face-on
      directions. The :C tip and :C face-on sites of sigma2 singlet carbenes tend to
      show negative and positive EPs, favoring nucleophiles and electrophiles,
      respectively; meanwhile, those of pi2 singlet carbenes, such as very highly pi
      conjugated 5-membered cyclic C(NCH)2, tend to show the opposite behavior. Open
      shell sigmapi singlet (such as highly pi-conjugated 5-membered cyclic C(CHCH)2)
      and triplet carbenes show less anisotropic and amphoteric behaviors.

PMID- 29570203
TI  - A single-molecule porphyrin-based switch for graphene nano-gaps.
AB  - Stable single-molecule switches with high on-off ratios are an essential
      component for future molecular-scale circuitry. Unfortunately, devices using gold
      electrodes are neither complementary metal-oxide-semiconductor (CMOS) compatible
      nor stable at room temperature. To overcome these limitations, several groups
      have been developing electroburnt graphene electrodes for single molecule
      electronics. Here, in anticipation of these developments, we examine how the
      electrical switching properties of a series of porphyrin molecules with pendant
      dipoles can be tuned by systematically increasing the number of spacer units
      between the porphyrin core and graphene electrodes. The porphyrin is sandwiched
      between a graphene source and drain and gated by a third electrode. It is found
      that the system has two stable states with high and low conductances, which can
      be controlled by coupling the dipole of the functionalised porphyrin to an
      external electric field. The associated rotation leads to the breaking of
      conjugation and a decrease in electrical conductances. As the number of spacers
      is increased, the conductance ratio can increase from 100 with one spacer to 200
      with four spacers. This switching ratio is further enhanced by decreasing the
      temperature, reaching approximately 2200 at 100 K. This design for a molecular
      switch using graphene electrodes could be extended to other aromatic systems.

PMID- 29570204
TI  - Spatially confined luminescence process in tip-modified heterogeneous-structured
      microrods for high-level anti-counterfeiting.
AB  - Recent years have witnessed the progress of lanthanide-doped materials from
      fundamental material synthesis to targeted practical applications such as optical
      applications in photodetection, anti-counterfeiting, volumetric display, optical
      communication, as well as biological imaging. The unique compositions and
      structures of well-designed lanthanide ion-doped materials could expand and
      strengthen their application performances. Herein, we report dual-mode
      luminescent crystalline microrods that spatially confine upconversion and
      downconversion photophysical process within defined regions using the specially
      designed heterogeneous structure. Through an epitaxial growth procedure,
      downconversion tips have been conjugated with the parent upconversion microrods
      in oriented directions. This spatially confined structure can effectively depress
      the deleterious energy depletion in lanthanide ions homogeneously doped
      materials, and as a result, the red, green, and blue upconversion intensities
      have been enhanced by 334, 225, and 22 times, respectively. Moreover, the induced
      tips hardly disturb the upconversion process of the microrod seeds. Upon 980 nm
      laser or ultraviolet lamp excitation, tunable emission colors were realized in
      the single tip-modified microrod, indicating potential applications of these
      microrods for high-level dual-mode anti-counterfeiting.

PMID- 29570205
TI  - Proteomic profile of 4-PBA treated human neuronal cells during ER stress.
AB  - Perturbations affecting the homoeostasis of endoplasmic reticulum (ER) activate
      an adaptive signaling known as the unfolded protein response or UPR. Many studies
      have reported the association between neurological disorders and ER stress.
      Decreasing ER stress may therefore aid in therapeutic control of neuronal
      diseases. Sodium 4-phenylbutyrate (4-PBA), a small molecule, has been shown to
      alleviate ER stress and various neurological diseases, but the mechanistic basis
      of its action is not well understood. Using an iTRAQ based LC-MS technique we
      have delineated the effect of 4-PBA on the proteome of human neuroblastoma cells
      (SK-N-SH) during Tunicamycin-induced ER stress. The proteomic profile of 4-PBA
      treated cells revealed that 4-PBA does not alter the cellular proteome to adapt
      towards ER stress. However, it can alleviate both the toxicity and proteomic
      alterations, induced by an ER stress inducer. Hence, the therapeutic effect of 4
      PBA is primarily due to its ability to resolve ER stress rather than its ability
      to alter the expression of proteins required for maintaining ER proteostasis.
      Thus, we posit here that 4-PBA acts as an authentic chemical chaperone by aiding
      protein folding in the ER.

PMID- 29570207
TI  - Silencing of c-Ski augments TGF-beta1-induced epithelial-mesenchymal transition
      in cardiomyocyte H9C2 cells.
AB  - BACKGROUND: The shRNA lentiviral vector was constructed to silence c-Ski
      expression in cardiac muscle cells, with the aim of exploring the role of c-Ski
      in transforming growth factor beta1 (TGF-beta1)-induced epithelial-mesenchymal
      transitions (EMT) in H9C2 cells. METHODS: RT-PCR and western blot were used to
      detect c-Ski expression at protein and messenger ribonucleic acid (mRNA) levels
      in 5 different cell lines. Then, lentiviral vector was constructed to silence or
      overexpress c-Ski in H9C2 cells. MTT and/or soft agar assay and transwell assay
      were used to detect cell proliferation and migration, respectively. The
      expression levels of c-Ski under different concentrations of TGF-beta1
      stimulation were detected by RT-qPCR and immunocytochemical analysis. In the
      presence or absence of TGF-beta1 stimulation, the proteins' expression levels of
      alpha-SMA, FN and E-cadherin, which are closely correlated with the process of
      EMT, were measured by western blot after c-Ski silencing or overexpression.
      Meanwhile, the effect of c-Ski on Samd3 phosphorylation with TGF-beta1
      stimulation was investigated. RESULTS: There is a high expression of c-Ski at
      protein and mRNA levels in H9C2 cell line, which first demonstrated the presence
      of c-Ski expression in H9C2 cells. Overexpression of c-Ski significantly
      increased H9C2 cell proliferation. The ability of c-Ski gene silencing to
      suppress cell proliferation was gradually enhanced, and inhibition efficiency was
      the highest after 6 to 7 d of transfection. Moreover, H9C2 cells with c-Ski
      knockdown gained significantly aggressive invasive potential when compared with
      the control group. TGF-beta1 stimulation could dose-independently reduce c-Ski
      expression in H9C2 cells and lead to obvious down-regulated expression of E
      cadherin. Interestingly, c-Ski could restore E-cadherin expression while
      suppressing alpha-SMA and/or FN expression stimulated by TGF-beta1. However,
      shRNA-induced c-Ski knockdown aggravated only the TGF-beta1-induced EMT.
      Moreover, c-Ski-shRNA also promoted the phosphorylation of Samd3 induced by TGF
      beta1. CONCLUSION: c-Ski expression in cardiac muscle cells could be down
      regulated by TGF-beta1. Silencing of c-Ski gene was accompanied by down
      regulation of E-cadherin, up-regulation of alpha-SMA and/or FN and Smad3
      phosphorylation induced by TGF-beta1, promoting EMT process. Therefore, c-Ski may
      be closely associated with TGF-beta1-induced EMT and play an important role in
      cardiac fibrosis development and progression.

PMID- 29570206
TI  - Participation in research improves overall patient management: insights from the
      Global Rheumatic Heart Disease registry (REMEDY).
AB  - BACKGROUND: Rheumatic heart disease (RHD) is a major public health problem in low
      and middle-income countries (LIMCs), with a paucity of high-quality trial data
      to improve patient outcomes. Investigators felt that involvement in a recent
      large, observational RHD study impacted positively on their practice, but this
      was poorly defined. AIM: The purpose of this study was to document the experience
      of investigators and research team members from LMICs who participated in a
      prospective, multi-centre study, the global Rheumatic Heart Disease Registry
      (REMEDY), conducted in 25 centres in 14 countries from 2010 to 2012. METHOD: We
      conducted an online survey of site personnel to identify and quantify their
      experiences. Telephone interviews were conducted with a subset of respondents to
      gather additional qualitative data. We asked about their experiences, positive
      and negative, and about any changes in RHD management practices resulting from
      their participation in REMEDY as a registry site. RESULTS: The majority of
      respondents in both the survey and telephone interviews indicated that
      participation as a registry site improved their management of RHD patients.
      Administrative changes included increased attention to follow-up appointments and
      details in patient records. Clinical changes included increased use of penicillin
      prophylaxis, and more frequent INR monitoring and contraceptive counselling.
      CONCLUSION: Our study demonstrates that participation in clinical research on RHD
      can have a positive impact on patient management. Furthermore, REMEDY has led to
      increased patient awareness and improved healthcare workers' knowledge and
      efficiency in caring for RHD patients.

PMID- 29570208
TI  - Sheep can be used as animal model of regional myocardial remodelling and
      controllable work.
AB  - BACKGROUND: A-V-sequential pacing has been shown to induce reversible conduction
      delay and subsequent asymmetric remodelling of the left ventricle (LV) in dogs
      and pigs. Both species have disadvantages in animal experiments. Therefore aim of
      this study focusses at developing a more feasible and easy-to-use animal model in
      sheep. METHODS: Dual-chamber pacing (DDD) pacemakers (right atrium + right
      ventricular free wall) were surgically implanted in 13 sheep. All animals
      underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were
      made at 110 bpm. RESULTS: DDD pacing acutely induced a left bundle branch block
      (LBBB) - like pattern with almost doubling in QRS width and septal flash,
      indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal
      ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals
      developed LV remodelling (confirmed with histology) with septal wall thinning (
      30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase
      (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and
      functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops,
      representing regional myocardial work, were recorded. Switching from AAI to DDD
      decreased immediately work in the septum and increased it in the lateral wall (
      69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax
      decreased (-27% and -25%, respectively, p < 0.05). CONCLUSIONS: Herein is
      developed a new sheep model with an asymmetrically remodelled LV. Simple
      pacemaker programming allows direct modulation of regional myocardial function
      and work. This model provides a new and valuable alternative for canine or
      porcine models and has the potential to become instrumental for investigating
      regional function and loading conditions on regional LV remodelling.

PMID- 29570209
TI  - Long-term outcomes of mitral valve annuloplasty versus subvalvular sparing
      replacement for severe ischemic mitral regurgitation.
AB  - BACKGROUND: Although practice guidelines recommend surgery for patients with
      severe chronic ischemic mitral regurgitation (CIMR), they do not specify whether
      to repair or replace the mitral valve. The purpose of this study was to evaluate
      the long-term outcomes in patients with severe CIMR undergoing mitral valve
      annuloplasty (MVA) versus subvalvular sparing mitral valve replacement (MVR).
      METHODS: 392 consecutive patients who underwent MVA or subvalvular sparing MVR
      for treatment of severe CIMR were retrospectively reviewed. RESULTS: After
      adjustment for baseline differences with multivariable regression analysis at 53
      monthsfollow-up (interquartile range, 34-81 months), there was no significant
      difference between the two groups for risk of major adverse cardiac or
      cerebrovascular events (MACCE), cardiac death, or all-cause death. Propensity
      score matching extracted 77 pairs. During the follow-up, compared with the MVR
      group, both the left atrium and left ventricle end-diastolic diameter were
      markedly larger (p = 0.013 and p = 0.033, respectively), and the incidence of
      mitral regurgitation recurrence was significantly higher in the MVA group (p <
      0.001). No significant difference was observed between the two propensity score
      matched groups in composite in-hospital outcomes, overall survival, freedom from
      cardiac death or MACCE, except subvalvular sparing MVR was associated with a
      lower incidence of hospitalization for heart failure than MVA (p = 0.015).
      CONCLUSIONS: Subvalvular sparing MVR is a suitable management of patients with
      severe CIMR, it is more favorable to ventricular remodeling and is associated
      with a lower incidence of hospitalization for heart failure than MVA.

PMID- 29570211
TI  - Valve in valve implantation of the CoreValve Evolut R in degenerated surgical
      aortic valves.
AB  - BACKGROUND: The new CoreValve Evolut R has an improved design to minimize
      paravalvular leak-age and allows repositioning of the valve. For patients with
      degenerated bioprosthetic aortic valves, transcatheter aortic valve implantation
      (TAVI) represents a less invasive option. Herein reported are valve-in-valve
      (ViV) implantations of this new valve. METHODS: A total of 26 patients (mean age
      79.4 +/- 6.1 years, 17 males and 9 females) were treated for severe prosthesis
      stenosis (n = 9), severe regurgitation (n = 8) or severe combination of stenosis
      and regurgitation (n = 9). All patients underwent transthoracic echocardiography
      before and after ViV implantation. RESULTS: Valve-in-valve implantation of a
      CoreValve Evolut R was performed successfully in all pa-tients. The mean
      transaortic gradient for stenotic valves determined by transthoracic
      echocardiography was reduced significantly from 37.5 +/- 15.3 mmHg in patients
      with prosthesis stenosis to 16.3 +/- 8.2 mmHg (p < 0.001). In all cases with
      severe prosthesis regurgitation, regurgitation was reduced to none or mild. All
      cause mortality after 30 days was 0%. CONCLUSIONS: It was concluded that
      CoreValve Evolut R is well suited for ViV implantation.

PMID- 29570210
TI  - Medium and long-term prognosis of transcatheter aortic valve implantation from
      the perspective of left ventricular diastolic function.
AB  - BACKGROUND: The effects of left ventricular (LV) diastolic function are well
      known in cardiac surgery, but unclear in transcatheter aortic valve implantation
      (TAVI). The objective of this study was to examine the association of
      preoperative LV diastolic function with medium to long-term outcomes of TAVI.
      METHODS: Eighty patients who underwent TAVI were classified into grades I, II and
      III based on preoperative LV diastolic function. Findings related to
      cardiovascular outcomes after TAVI were extracted retrospectively from clinical
      and echocardiographic data and relationships with diastolic function were
      examined. RESULTS: The average follow-up was 529 days (interquartile range {IQR]
      358-741 days). Cardiovascular events occurred in 17 cases, including 6 deaths,
      and were significantly associated with Euro II score (p = 0.043), albumin level
      (p = 0.026), coronary artery disease (CAD) (p = 0.017), and diastolic function (p
      < 0.001). The 360-day event-free rates were 89.5%, 89.5% and 37.5% for grades I,
      II and III (p = 0.00013). Median event-free survival (EFS) in grade III cases was
      180 days. In a Cox proportional hazard model, LV diastolic dysfunction (hazard
      ratio [HR]3.99, 95% confidence interval [CI] 1.35-11.80, p = 0.012) and low
      albumin (HR 4.73, 95% CI 1.42-15.80, p = 0.012) were significant independent
      predictors of reduced EFS. CONCLUSIONS: Medium to long-term outcomes of TAVI were
      poorer in patients with deteriorated LV diastolic function, and outcomes in grade
      III cases were significantly worse than those in grade I and II cases.
      Preoperative LV diastolic function may be useful in prediction of outcomes after
      TAVI.

PMID- 29570212
TI  - How does the risk of cardiovascular death and cardiovascular risk factor profiles
      differ between socioeconomic classes in Poland: A country in transition.
AB  - BACKGROUND: Socioeconomic status (SES) is an important factor of cardiovascular
      diseases (CVD) development. A decline in death from CVD among subjects with high
      SES is observed in developed countries. The aim of this study was to assess
      differences in cardiovascular risk between socioeconomic classes in Poland, a
      country currently in transition. METHODS: A sample of 15200 people was drawn. A
      three stage selection was performed. Eventually, 6170 patients were examined
      (2013/2014). Data was collected using a questionnaire in face-to-face interviews,
      anthropometric data and blood tests were also obtained. Education was categorized
      as incomplete secondary, secondary and higher than secondary school. Monthly
      income per person was categorized as low (<= 1000 PLN), medium (1001-2000 PLN)
      and high (>= 2001 PLN). Education and income groups were analyzed by prevalence
      of CVD risk factors and high CVD risk (SCORE >= 5%). RESULTS: Higher education
      was associated with lower prevalence of all analyzed CVD risk factors (p <
      0.001), having the highest income with lower prevalence of hypertension,
      currently smoking, obesity and lower HDL-cholesterol. Multivariable analysis
      showed that frequency of high CVD risk decreased with increasing education level
      (OR 0.61; 95% CI 0.49-0.76; p < 0.01), a similar favorable impact of higher
      income on high CVD risk was demonstrated in the whole group (OR 0.81; 95% CI 0.67
      0.99; p = 0.04). CONCLUSIONS: SES is an independent predictor of high
      cardiovascular (CV) risk of death. A favorable impact on the prevalence of high
      CV risk was demonstrated for education and partly for income in the whole group.
      It may reflect a transition being undergone in Poland, moreover, it predicts how
      socioeconomic factors may generate health inequalities in other transitioning
      countries.

PMID- 29570213
TI  - Case of childhood granulomatous periorificial dermatitis.

PMID- 29570214
TI  - Distance learning for maternal and child health nurses and midwives in Mongolia:
      a qualitative evaluation.
AB  - BACKGROUND: Continuing education is vital for the development of the competencies
      of nurses and midwives. We analysed the effectiveness of a distance education
      programme for maternal and child health nurses and midwives in Mongolia,
      assessing its strengths and limitations and ways in which it could be improved.
      The aim of this research is to provide an analysis of the successes and failures
      of the programme, in order to improve future versions of this and similar
      programmes in Mongolia and elsewhere. METHODS: We carried out a qualitative
      descriptive study in Mongolia in August 2015. This consisted of three semi
      structured interviews and two focus groups in the Second National Hospital,
      Ulaanbaatar, and three semi-structured interviews and one focus group in
      Dornogovi Provincial Maternal Hospital, Sainshand, Dornogovi Province. In total,
      there were 22 participants in our research. Data from the interviews and focus
      groups were thematically coded and analysed using NVivo version 10. FINDINGS: The
      distance education programme is well received by participants. They suggest that
      it has improved their clinical practice and education in a number of areas, and
      are anxious for the programme to continue. A number of alterations would be
      necessary to improve both the quality of the programme and the ability of
      participants to foster change on the basis of what they have learnt. This
      provides challenges for both the programme organizers and the providers of
      maternal and child health services in Mongolia. IMPLICATIONS FOR NURSING AND/OR
      HEALTH POLICY: The success of the distance education programme suggests that
      collaborations of this type are a cost-effective method of disseminating best
      practice in policy and practice to improve the quality of care provided to
      mothers and children in low-resource settings. CONCLUSIONS: A distance education
      programme is vital to link maternal care providers in Mongolia to new trends in
      care. Mongolia's relative isolation means that this programme is particularly
      valuable there. However, the programme could work equally well in other
      developing country settings.

PMID- 29570215
TI  - Functional lifespans of xylem vessels: Development, hydraulic function, and post
      function of vessels in several species of woody plants.
AB  - PREMISE OF THE STUDY: Xylem vessels transition through different stages during
      their functional lifespan, including expansion and development of vessel
      elements, transition to vessel hydraulic functionality, and eventual transition
      to post-functionality. We used information on vessel development and function to
      develop a model of vessel lifespan for woody plants. METHODS: We examined vessel
      functional lifespan using repeated anatomical sampling throughout the growing
      season, combined with active-xylem staining to evaluate vessel hydraulic
      transport functionality. These data were combined with a literature review. The
      transitions between vessel functional lifespans for several species are
      illustrated, including grapevine (Vitis vinifera L., Vitaceae), English oak
      (Quercus robur L., Fagaceae), American chestnut [Castanea dentata (Marshall)
      Borkh.; Fagaceae], and several arid and semi-arid shrub species. KEY RESULTS: In
      intact woody plants, development and maturation of vessel elements may be
      gradual. Once hydraulically functional, vessel elements connect to form a vessel
      network that is responsible for bulk hydraulic flow through the xylem. Vessels
      become nonfunctional due to the formation of gas emboli. In some species and
      under some conditions, vessel functionality of embolized conduits may be restored
      through refilling. Blockages, such as tyloses, gels, or gums, indicate permanent
      losses in hydraulic functional capacity; however, there may be some interesting
      exceptions to permanent loss of functionality for gel-based blockages.
      CONCLUSIONS: The gradual development and maturation of vessel elements in woody
      plants, variation in the onset of functionality between different populations of
      vessels throughout the growing season, and differences in the timing of vessel
      transitions to post-functionality are important aspects of plant hydraulic
      function.

PMID- 29570216
TI  - Cardiac resynchronization therapy: A comparative analysis of mortality in African
      Americans and Caucasians.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients
      with heart failure, reduced left ventricular ejection fraction, and a prolonged
      QRS duration. African Americans are underrepresented in clinical trials and CRT
      is underutilized; consequently, the benefits and outcomes of CRT are not well
      defined. METHODS: We evaluated 294 patients, determined survival using Kaplan
      Meier analysis, and used Cox proportional hazards regression model to determine
      predictors of mortality. Propensity score-match analysis was applied to balance
      covariates in African Americans and Caucasians. RESULTS: The mean age for African
      Americans (n  =  131) and Caucasians (n  =  163) was 65 +/- 12 and 70 +/- 13
      years (P  =  0.0003). Mortality in African Americans was 28% compared to 37% in
      Caucasians (P  =  0.14) over a median follow-up of 8.1 +/- 0.6 years. Survival
      was significantly reduced in African Americans and Caucasians with a glomerular
      filtration rate (GFR) < 60 (6.7 +/- 0.4, 95% confidence interval [CI]: 5.9-7.5 vs
      8.6 +/- 0.5 CI: 7.7-9.5 years, P  =  0.005), and those not treated with an
      aldosterone antagonist (7.1 +/- 0.4, 95% CI: 6.5-7.9 vs 8.7 +/- 0.6, 7.6-9.9
      years, P  =  0.04), respectively. Independent predictors of mortality were a GFR
      <60 and low left ventricular ejection fraction. In African Americans, ischemic
      cardiomyopathy (ICM) and lack of therapy with an angiotensin-converting enzyme
      inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were associated with
      increased mortality. CONCLUSIONS: Long-term survival benefit from CRT was similar
      in African Americans and Caucasians. A GFR < 60 and lack of therapy with an
      aldosterone antagonist were associated with decreased survival. Survival also was
      inversely related to the number of comorbidities. In African Americans,
      underutilization of an ACEI or ARB, and ICM were additional factors associated
      with increased mortality.

PMID- 29570217
TI  - Impact of apheresis automation on procedure quality and predictability of CD34+
      cell yield.
AB  - Success of peripheral blood stem cell (PBSC) collections depends on patient
      biological parameters and stable apheresis device performance. We investigated
      product quality and factors influencing main apheresis procedure outcomes
      including CD34+ collection efficiency (CE), product volume or platelet CE. We
      also assessed different CD34+ cell yield prediction algorithms. Autologous PBSC
      collections by Spectra Optia from myeloma and lymphoma patients were analyzed.
      Complete blood count (CBC) from patient preprocedure and from collected products
      were assessed. (1) Product yield was calculated, (2) Product CBC was correlated
      with patient preprocedure variables, and (3) Predictions of CD34+ yields based on
      (a) product CD34+ cell concentration in samples after two or four chamber flushes
      or (b) traditional CE2 benchmark, were compared. 62 procedures in 41 patients
      were analyzed. 84% of all procedures were run without operator intervention.
      Median CD34+ CE2 was 56.9% (48.8%-65.2%) and quite stable irrespective of patient
      conditions, with minor influence from patient white blood cell (WBC) precounts
      (rs  = -.47; P < .001). Platelet loss correlated with WBC precount (rs  = .46; P
      < .001), product volume (rs  = .71; P < .0001) and number of chambers collected
      (rs  = .72; P < .0001). CD34+ cell yield was better predicted based on (a)
      product CD34+ cell concentration from samples after 2 and 4 chamber flushes,
      respectively (rs  = .969; P < .0001 and rs  = .9648; P < .0001) than based on (b)
      CE2 formula (rs  = .8262, P < .0001). Spectra Optia provides good quality PBSC
      products with stable and predictable yield regardless of starting conditions.
      CD34+ sampling of product after few chamber flushes could be used to predict
      CD34+ yield.

PMID- 29570218
TI  - Analyzing linear spatial features in ecology.
AB  - The spatial analysis of dimensionless points (e.g., tree locations on a plot map)
      is common in ecology, for instance using point-process statistics to detect and
      compare patterns. However, the treatment of one-dimensional linear features
      (fiber processes) is rarely attempted. Here we appropriate the methods of vector
      sums and dot products, used regularly in fields like astrophysics, to analyze a
      data set of mapped linear features (logs) measured in 12 * 1-ha forest plots. For
      this demonstrative case study, we ask two deceptively simple questions: do trees
      tend to fall downhill, and if so, does slope gradient matter? Despite noisy data
      and many potential confounders, we show clearly that topography (slope direction
      and steepness) of forest plots does matter to treefall. More generally, these
      results underscore the value of mathematical methods of physics to problems in
      the spatial analysis of linear features, and the opportunities that
      interdisciplinary collaboration provides. This work provides scope for a variety
      of future ecological analyzes of fiber processes in space.

PMID- 29570219
TI  - Advanced glycation end-products suppress autophagic flux in podocytes by
      activating mammalian target of rapamycin and inhibiting nuclear translocation of
      transcription factor EB.
AB  - Insufficient autophagy in podocytes is related to podocyte injury in diabetic
      nephropathy (DN). Advanced glycation end-products (AGEs) are major factors of
      podocyte injury in DN. However, the role and mechanism of AGEs in autophagic
      dysfunction remain unknown. We investigated autophagic flux in AGE-stimulated
      cultured podocytes using multiple assays: western blotting, reverse transcription
      quantitative PCR, immunofluorescence staining, and electron microscopy. We also
      utilized chloroquine and a fluorescent probe to monitor the formation and
      turnover of autophagosomes. Mice of the db/db strain were used to model diabetes
      mellitus (DM) with high levels of AGEs. To mimic DM with normal levels of AGEs as
      a control, we treated db/db mice with pyridoxamine to block AGE formation. AGEs
      impaired autophagic flux in the cultured podocytes. Compared with db/db mice with
      normal AGEs but high glucose levels, db/db mice with high AGEs and high glucose
      levels exhibited lower autophagic activity. Aberrant autophagic flux was related
      to hyperactive mammalian target of rapamycin (mTOR), a major suppressor of
      autophagy. Pharmacologic inhibition of mTOR activity restored impaired autophagy.
      AGEs inhibited the nuclear translocation and activity of the pro-autophagic
      transcription factor EB (TFEB) and thus suppressed transcription of its several
      autophagic target genes. Conversely, TFEB overexpression prevented AGE-induced
      autophagy insufficiency. Attenuating mTOR activity recovered TFEB nuclear
      translocation under AGE stimulation. Co-immunoprecipitation assays further
      demonstrated the interaction between mTOR and TFEB in AGE-stimulated podocytes
      and in glomeruli from db/db mice. In conclusion, AGEs play a crucial part in
      suppressing podocyte autophagy under DM conditions. AGEs inhibited the formation
      and turnover of autophagosomes in podocytes by activating mTOR and inhibiting the
      nuclear translocation of TFEB. (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- 29570220
TI  - CETP and LCAT Gene Polymorphisms Are Associated with High-Density Lipoprotein
      Subclasses and Acute Coronary Syndrome.
AB  - We evaluated whether CETP and LCAT gene polymorphisms are statistically
      associated with the high-density lipoprotein (HDL) size distribution, the
      cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS)
      susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT
      polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619
      patients with ACS and 607 control individuals. For HDL analysis, a subgroup of
      100 healthy individuals was recruited; the HDL subclasses were separated via
      ultracentrifugation and polyacrylamide gradient gel electrophoresis under native
      conditions. Under a dominant model, the G allele of the rs708272 polymorphism was
      associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p
      value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of
      the eight possible combinations was associated with the risk of developing ACS
      (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary
      atherosclerosis. The rs708272 G allele carriers had a lower concentration of
      cholesterol associated with the HDL2a and HDL3a subclasses when compared with
      subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a
      lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison
      to the GG genotype; the cholesterol associated with the each one of the five HDL
      subclasses was significantly lower in rs2292318 A than in GG subjects. In
      summary, this study demonstrates that the rs708272 polymorphism is associated
      with a heightened risk of developing ACS. In addition, we report the association
      of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.

PMID- 29570222
TI  - Role of soluble CD147 in psoriatic patients: A preliminary study.

PMID- 29570221
TI  - Effects of calcium and its interaction with phosphorus on the nutrient status and
      growth of three Lupinus species.
AB  - Phosphorus (P)-deficiency symptoms are known for Lupinus species grown in
      calcareous soil, but we do not know if this is due to a high calcium (Ca)
      availability or a low P availability in the soil. To address this problem, we
      explored both the effects of Ca and its interactions with P on nutrient status
      and growth of three Lupinus species. Two Ca-sensitive genotypes (L. angustifolius
      L. P26723 and L. cosentinii Guss. P27225) and two Ca-tolerant genotypes (L.
      angustifolius L. cv Mandelup and L. pilosus Murr. P27440) were grown
      hydroponically at two P (0.1 and 10 MUM) and three Ca (0.1, 0.6 and 6 mM) levels.
      Leaf symptoms and biomass were recorded, whole leaf and root nutrient
      concentrations were analysed, and leaf cellular P and Ca concentrations were
      determined. Phosphorus-deficiency symptoms were only observed in the Ca-sensitive
      genotypes. Among all the genotypes in this study, the Ca-tolerant L. pilosus
      showed an ability to maintain stable leaf Ca and P concentrations whereas the Ca
      tolerant L. angustifolius cv Mandelup did not maintain a stable whole leaf Ca
      concentration, but maintained a low cytosolic Ca2+ concentration through
      effective Ca compartmentation. However, the two Ca-sensitive genotypes, L.
      angustifolius P26723 and L. cosentinii, did not exhibit an ability to maintain a
      stable whole leaf Ca concentration or effectively compartmentalise Ca. Therefore,
      having the capacity to maintain a stable whole leaf Ca concentration or
      effectively compartmentalising Ca in leaves are likely critical for Lupinus
      species to be Ca tolerant.

PMID- 29570223
TI  - An investigation of the monoamine oxidase inhibition properties of pyrrolo[3,4
      f]indole-5,7-dione and indole-5,6-dicarbonitrile derivatives.
AB  - Hit, Lead & Candidate Discovery In recent studies, we have shown that pyrrolo[3,4
      f]indole-5,7-dione and indole-5,6-dicarbonitrile derivatives act as good potency
      in vitro inhibitors of the monoamine oxidase (MAO) enzymes. To expand on these
      series and to further derive structure-activity relationships (SARs) for MAO
      inhibition, in the present study we synthesized additional homologs and related
      analogs of these chemical classes. Analyzes of the MAO inhibition properties of
      the synthesized compounds show that among the pyrrolo[3,4-f]indole-5,7-dione
      derivatives good potency MAO inhibitors exist as exemplified by 10, which
      possesses IC50 values for the inhibition of MAO-A and MAO-B of 0.023 and 0.178
      uM, respectively. Among thirteen pyrrolo[3,4-f]indole-5,7-diones, nine compounds
      exhibit IC50 values for the inhibition of an MAO isoform in the submicromolar
      range. It may be concluded that active MAO inhibitors, such as 10 represent
      suitable leads for the development of drugs for neurodegenerative and
      neuropsychiatric disorders such as Parkinson's disease and depression. MAO
      inhibitors are also of interest for the treatment of prostate cancer, certain
      types of cardiomyopathies and Alzheimer's disease.

PMID- 29570224
TI  - A rare missense mutation in GJB3 (Cx31G45E) is associated with a unique cellular
      phenotype resulting in necrotic cell death.
AB  - Erythrokeratodermia variabilis et progressiva (EKV-P) is caused by mutations in
      either the GJB3 (Cx31) or GJB4 genes (Cx30.3). We identified a rare GJB3 missense
      mutation, c.134G>A (p.G45E), in two unrelated patients and investigated its
      cellular characteristics. Expression of Cx31G45E-GFP caused previously
      undescribed changes within HeLa cells and HaCaT cells, a model human keratinocyte
      cell line. Cx31WT-GFP localised to the plasma membrane, but expression of
      Cx31G45E-GFP caused vacuolar expansion of the endoplasmic reticulum (ER), the
      mutant protein accumulated within the ER membrane and disassembly of the
      microtubular network occurred. No ER stress responses were evoked. Cx31WT-myc-myc
      6xHis and Cx31G45E-GFP co-immunoprecipitated, indicative of heteromeric
      interaction, but co-expression with Cx31WT-mCherry, Cx26 or Cx30.3 did not
      mitigate the phenotype. Cx31 and Cx31G45E both co-immunoprecipitated with Cx43,
      indicating the ability to form heteromeric connexons. WT-Cx31 and Cx43 assembled
      into large gap junction plaques at points of cell-to-cell contact; Cx31G45E
      restricted the ability of Cx43 to reach the plasma membrane in both HaCaT cells
      and HeLa cells stably expressing Cx43 where the proteins strongly co-localised
      with the vacolourised ER. Cell viability assays identified an increase in cell
      death in cells expressing Cx31G45E-GFP, which FACS analysis determined was
      necrotic. Blocking connexin channel function with 18alpha-glycyrrhetinic acid did
      not completely rescue necrosis or prevent propidium iodide uptake, suggesting
      that expression of Cx31G45E-GFP damages the cellular membrane independent of its
      channel function. Our data suggest that entrapment of Cx43 and necrotic cell
      death in the epidermis could underlie the EKV skin phenotype.

PMID- 29570225
TI  - Hidradenitis suppurativa in association with keratitis-ichthyosis-deafness
      syndrome treated with adalimumab.

PMID- 29570226
TI  - Cutaneous angiosarcoma: the role of dermoscopy to reduce the risk of a delayed
      diagnosis.

PMID- 29570227
TI  - The effect of polyploidization on tree hydraulic functioning.
AB  - PREMISE OF THE STUDY: Recent research has highlighted the importance of living
      tissue in wood. Polyploidization can impact amounts and arrangements of living
      cells in wood, potentially leading to increased drought tolerance. Tetraploid
      variants were created from the apple cultivar Malus *domestica 'Gala' (Gala-4x),
      and their vulnerability to drought-induced cavitation and their hydraulic
      capacitance were compared to those of their diploid predecessors (Gala-2x).
      Assuming a positive correlation between polyploidy and drought tolerance, we
      hypothesized lower vulnerability and higher capacitance for the tetraploid.
      METHODS: Vulnerability to drought-induced cavitation and the hydraulic
      capacitance were quantified through acoustic emission and continuous weighing of
      shoots during a bench-top dehydration experiment. To underpin the hydraulic trait
      results, anatomical variables such as vessel area, conduit diameter, cell wall
      reinforcement, and ray and vessel-associated parenchyma were measured. KEY
      RESULTS: Vulnerability to drought-induced cavitation was intrinsically equal for
      both ploidy variants, but Gala-4x proved to be more vulnerable than Gala-2x
      during the early phase of desiccation as was indicated by its significantly lower
      air entry value. Higher change in water content of the leafy shoot, higher amount
      of parenchyma, and larger vessel area and size resulted in a significantly higher
      hydraulic capacitance and efficiency for Gala-4x compared to Gala-2x.
      CONCLUSIONS: Both ploidy variants were typified as highly sensitive to drought
      induced cavitation, with no significant difference in their overall drought
      vulnerability. But, when water deficit is short and moderate, Gala-4x may delay a
      drought-induced decrease in performance by trading hydraulic safety for increased
      release of capacitively stored water from living tissue.

PMID- 29570229
TI  - Ecological data for western Indian Ocean tuna.
AB  - Tuna are marine apex predators that inhabit the tropical and sub-tropical waters
      of the Indian Ocean where they support socially and economically important
      fisheries. Key component of pelagic communities, tuna are bioindicator species of
      anthropogenic and climate-induced changes through modifications of the structure
      and related energy-flow of food webs and ecosystems. The IndianEcoTuna dataset
      provides a panel of ecological tracers measured in four soft tissues (white
      muscle, red muscle, liver, gonads) from 1,364 individuals of four species, i.e.,
      the albacore (ALB, Thunnus alalunga), the bigeye (BET, T. obesus), the skipjack
      (SKJ, Katsuwomus pelamis), and the yellowfin (YFT, T. albacares), collected
      throughout the western Indian Ocean from 2009 to 2015. Sampling was carried out
      during routine monitoring programs, at sea by observers onboard professional
      vessels or at landing. For each record, the type of fishing gear, the
      conservation mode, as well as the fishing date and catch location are provided.
      Individuals were sampled to span a wide range of body sizes: 565 ALB with fork
      length from 58 to 118 cm, 155 BET from 29.5 to 173 cm, 304 SKJ from 30 to 74 cm,
      and 340 YFT from 29 to 171.5 cm. The IndianEcoTuna dataset combines: (1) 9,512
      records of carbon and nitrogen stable isotopes (percent element weights, delta13
      C and delta15 N values) in 1,185 fish, (2) 887 concentrations of total proteins
      in 242 fish, (3) 8,356 concentrations of total lipids and three lipid classes
      (triacylglycerols TAG; phospholipids PL; sterols ST) in 695 fish, and (4) 1,150
      and 1,033 profiles of neutral and polar fatty acids in 397 and 342 fish,
      respectively. Information on sex and weights of the whole fish, gonads, liver and
      stomach is provided. Because of the essential trophic role and wide-ranging of
      tuna in marine systems, and the large panel of tropho-energetic tracers and
      derived-key quantitative parameters provided (e.g., niche width, trophic
      position, condition indices), the IndianEcoTuna dataset should be of high
      interest for global and regional research on marine trophic ecology and food web
      analysis, as well as on the impacts of anthropogenic changes on Indian Ocean
      marine ecosystems. There are no copyright restrictions for research and/or
      teaching purposes. Usage of the dataset must include citation of this Data Paper.

PMID- 29570230
TI  - Association between the age of solid food introduction and eczema: A systematic
      review and a meta-analysis.
AB  - INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable
      disease burden. Both timing of introduction to solid food and allergenic food are
      believed to be related to childhood eczema. Despite the growing body of evidence,
      the relationship between timing of any solid food introduction (allergenic and/or
      non-allergenic) and development of eczema has not previously been systematically
      reviewed. METHODS: PubMed and EMBASE databases were searched using food and
      eczema terms. Two authors selected papers according to the inclusion criteria and
      extracted information on study characteristics and measures of association. Meta
      analyses were performed after grouping studies according to the age and type of
      exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting
      results from 16 study populations. Of these, 11 were cohort studies, 2 case
      controls, 1 cross-sectional study and 2 randomized controlled trials. Limited
      meta-analyses were performed due to heterogeneity between studies. Timing of
      solid food introduction was not associated with eczema. One randomized controlled
      trial provided weak evidence of an association between early allergenic (around 4
      months) food introduction and reduced risk of eczema. CONCLUSIONS: The available
      evidence is currently insufficient to determine whether the timing of
      introduction of any solid food influences the risk of eczema.

PMID- 29570232
TI  - STX2 is a causative gene for nonobstructive azoospermia.
AB  - STX2 encodes a sulfoglycolipid transporter. Although Stx2 nullizygosity is known
      to cause spermatogenic failure in mice, STX2 mutations have not been identified
      in humans. Here, we performed STX2 mutation analysis for 131 Japanese men
      clinically diagnosed with nonobstructive azoospermia. As a result, we identified
      a homozygous frameshift mutation [c.8_12delACCGG, p.(Asp3Alafs*8)] in one
      patient. The mutation-positive patient exhibited loss-of-heterozygosity for 58.4
      Mb genomic regions involving STX2, suggesting possible parental consanguinity.
      The patient showed azoospermia, relatively small testes, and a mildly elevated
      follicle stimulating hormone level, but no additional clinical features.
      Testicular histology of the patient showed universal maturation arrest and
      multinucleated spermatocytes, which have also been observed in mice lacking Stx2.
      PCR-based cDNA screening revealed wildtype STX2 expression in various tissues
      including the testis. Our results indicate that STX2 nullizygosity results in
      nonsyndromic maturation arrest with multinucleated spermatocytes, and accounts
      for a small fraction of cases with nonobstructive azoospermia.

PMID- 29570233
TI  - Direct production of dihydroxylated sesquiterpenoids by a maize terpene synthase.
AB  - The astounding structural and biological diversities of the large class of
      terpenoid natural products are imparted by both their complex hydrocarbon
      backbones and further elaboration by the addition of multiple hydroxyl groups,
      which provide both solubility and specific binding properties. While the role of
      terpene synthases (TPSs) in generating hydrocarbons with complex backbones is
      well known, these also are known to generate (singly) hydroxylated products by
      the addition of water prior to terminating deprotonation. Here a maize
      sesquiterpene synthase was unexpectedly found to generate dually hydroxylated
      products directly from (E,E)-farnesyl diphosphate, primarily eudesmane-2,11-diol,
      along with two closely related structural isomers. The unprecedented formation of
      these diols was proposed to proceed via initial addition of water to a
      germacradienyl+ intermediate, followed by protonation of the internal carbon-6,7
      double-bond in the resulting hedycarol, with subsequent cyclization and further
      addition of water to an eudesmolyl+ intermediate. Evidence for the proposed
      mechanism was provided by labeling studies, as well as site-directed mutagenesis,
      based on structural modeling, which identified an active site phenylalanine
      required for the protonation and further elaboration of hedycaryol. This
      dihydroxylated sesquiterpenoid synthase was specifically expressed in maize roots
      and induced by pathogen infection, with its major enzymatic product only detected
      in root exudates or infected roots, suggesting a role in defense. Regardless of
      the ultimate metabolic fate or physiological role of these diols, this report not
      only reveals an unanticipated extension of the catalytic prowess of TPSs, but
      also provides insight into the underlying enzymatic mechanism.

PMID- 29570231
TI  - A Comparative In Vivo Study of Albumin-Coated Paclitaxel Nanocrystals and
      Abraxane.
AB  - Nanoparticulate drug carriers exploit the enhanced permeability of tumor
      vasculature to achieve selective delivery of chemotherapeutic drugs. For this
      purpose, nanoparticles (NPs) need to circulate with a long half-life, enter
      tumors via the permeable vasculature and stay in tumors via favorable
      interactions with tumor cells. To fulfill these requirements, albumin-coated
      nanocrystal formulation of paclitaxel (PTX), Cim-F-alb, featuring high drug
      loading content, physical stability in serum, and surface-bound albumin in its
      native conformation is prepared. The pharmacokinetic and biodistribution (PK/BD)
      profiles of Cim-F-alb in a mouse model of B16F10 melanoma show that Cim-F-alb
      exhibits a longer plasma half-life and a greater PTX deposition in tumors than
      Abraxane by ~1.5 and ~4.6 fold, respectively. Biolayer interferometry analysis
      indicates that Cim-F-alb has less interaction with serum proteins than
      nanocrystals lacking albumin coating, indicating the protective effect of the
      surface-bound albumin against opsonization in the initial deposition phase. With
      the advantageous PK/BD profiles, Cim-F-alb shows greater and longer-lasting
      anticancer efficacy than Abraxane at the equivalent dose. This study demonstrates
      the significance of controlling circulation stability and surface property of NPs
      in efficient drug delivery to tumors and enhanced anticancer efficacy.

PMID- 29570234
TI  - Pilot study utilizing Fluorine-18 fluorodeoxyglucose-positron emission
      tomography/computed tomography for glycolytic phenotyping of canine mast cell
      tumors.
AB  - The goal of this prospective pilot study was to use naturally occurring canine
      mast cell tumors of various grades and stages as a model for attempting to
      determine how glucose uptake and markers of biologic behavior are correlated. It
      was hypothesized that enhanced glucose uptake, as measured by 2-[fluorine
      18]fluoro-d-glucose-positron emission tomography/computed tomography (F18 FDG PET
      CT), would correlate with histologic grade. Dogs were recruited for this study
      from a population referred for treatment of cytologically or histologically
      confirmed mast cell tumors. Patients were staged utilizing standard of care
      methods (abdominal ultrasound and three view thoracic radiographs), followed by a
      whole body F18 FDG PET-CT. Results of the F18 FDG PET-CT were analyzed for
      possible metastasis and standard uptake value maximum (SUVmax ) of identified
      lesions. Incisional or excisional biopsies of the accessible mast cell tumors
      were obtained and histology performed. Results were then analyzed to look for a
      possible correlation between the grade of mast cell tumors and SUVmax . A total
      of nine animals were included in the sample. Findings indicated that there was a
      correlation between grade of mast cell tumors and SUVmax as determined by F18 FDG
      PET-CT (p-value = 0.073, significance <= 0.1). Based on the limited power of this
      study, it is felt that further research to examine the relationship between
      glucose utilization and biologic aggressiveness in canine mast cell tumors is
      warranted. This study was unable to show that F18 FDG PET-CT was a better staging
      tool than standard of care methods.

PMID- 29570235
TI  - Adjustable Intermolecular Interactions Allowing 2D Transition Metal
      Dichalcogenides with Prolonged Scavenging Activity for Reactive Oxygen Species.
AB  - There is an increasing demand for control over the dimensions and functions of
      transition metal dichalcogenides (TMDs) in aqueous solution toward biological and
      medical applications. Herein, an approach for the exfoliation and
      functionalization of TMDs in water via modulation of the hydrophobic interaction
      between poly(epsilon-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) and the
      basal planes of TMDs is reported. Decreasing the hydrophobic PCL length of PCL-b
      PEG from 5000 g mol-1 (PCL5000 ) to 460 g mol-1 (PCL460 ) significantly increases
      the exfoliation efficiency of TMD nanosheets because the polymer-TMD hydrophobic
      interaction becomes dominant over the polymer-polymer interaction. The TMD
      nanosheets exfoliated by PCL460 -b-PEG5000 (460-WS2 , 460-WSe2 , 460-MoS2 , and
      460-MoSe2 ) show excellent and prolonged scavenging activity for reactive oxygen
      species (ROS), but each type of TMD displays a different scavenging tendency
      against hydroxyl, superoxide, and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) radicals. A mechanistic study based on electron paramagnetic
      resonance spectroscopy and density functional theory simulations suggests that
      radical-mediated oxidation of TMDs and hydrogen transfer from the oxidized TMDs
      to radicals are crucial steps for ROS scavenging by TMD nanosheets. As-prepared
      460-TMDs are able to effectively scavenge ROS in HaCaT human keratinocytes, and
      also exhibit excellent biocompatibility.

PMID- 29570236
TI  - Allied health weekend service provision in Australian rehabilitation units.
AB  - OBJECTIVES: To determine current Australian allied health rehabilitation weekend
      service provision and to identify perceived barriers to and facilitators of
      weekend service provision. METHODS: Senior physiotherapists from Australian
      rehabilitation units completed an online cross-sectional survey exploring current
      service provision, staffing, perceived outcomes, and barriers and facilitators to
      weekend service provision. RESULTS: A total of 179 (83%) eligible units
      responded, with 94 facilities (53%) providing weekend therapy. A Saturday service
      was the most common (97%) with the most frequent service providers being
      physiotherapists (90%). Rehabilitation weekend service was perceived to increase
      patient/family satisfaction (66%) and achieve faster goal attainment (55%).
      Common barriers were budgetary restraints (66%) and staffing availability (54%),
      with facilitators including organisational support (76%), staff availability
      (62%) and staff support (61%). CONCLUSION: Despite increasing evidence of
      effectiveness, only half of Australian rehabilitation facilities provide weekend
      services. Further efforts are required to translate evidence from clinical trials
      into feasible service delivery models.

PMID- 29570238
TI  - Relationship between individual and family characteristics and psychosocial
      factors in persons with familial pancreatic cancer.
AB  - OBJECTIVE: Describe relationships between self-reported personal demographics or
      familial characteristics and psychosocial outcomes (Patient Reported Outcome
      Measurement Information System Global Health, Impact of Event Scale-Revised
      [pancreatic cancer risk-related distress], cancer risk perception, and cancer
      worry) in participants with inherited or familial pancreatic cancer risk.
      METHODS: A multisite cross sectional survey of adults with elevated pancreatic
      cancer risk based on family history. All variables were summarized with
      descriptive statistics. To assess univariate associations, t test and chi
      square/Fisher's exact test were used, and backward model selection was used in
      multivariable analysis. RESULTS: Respondents (N = 132) reported moderate to high
      frequency of cancer worry and 59.3% perceived a 50% or more perceived lifetime
      risk for pancreatic cancer, which far exceeds objective risk estimates. Cancer
      worry was associated with female gender (P = .03) and pancreatic cancer risk
      specific distress (P = .05). Higher-risk perception was associated with having a
      high school education or less (P = .001), higher distress (P = .02), and cancer
      worry (P = .008) and family cancer death experience (P = .02). Higher distress
      was associated with experience as a caregiver to a seriously ill family member in
      the past 5 years (P = .006). CONCLUSIONS: Individuals with inherited or familial
      pancreatic cancer risk experience cancer worry, distress, and have increased risk
      perception, particularly in the period following caring for a loved one with
      cancer. Routine evaluation of distress in this setting, as well as the
      development of supportive care resources, will help support patients living with
      risk for pancreatic cancer.

PMID- 29570237
TI  - Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant
      recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) viremia after CD34+ -selected hematopoietic
      stem cell transplant (HCT) often requires prolonged antiviral therapy. We report
      rates and outcomes of resistant CMV in a contemporary cohort of CD34+ -selected
      HCT recipients managed preemptively. METHODS: We retrospectively reviewed 220
      consecutive, CMV-seropositive recipients (R+), who received CD34+ -selected HCT
      at Memorial Sloan Kettering Cancer Center between June 2010 and December 2014.
      Patients were monitored by quantitative CMV PCR and were treated preemptively.
      CMV resistance was tested by a genotypic assay. RESULTS: One hundred and sixty
      one (73%) patients developed CMV viremia and 47 (29% of viremic and 21% of total
      patients) had CMV resistance testing by one-year from HCT. CMV resistance was
      confirmed in 19 (12% of viremic and 9% of total) patients and was identified >3
      months from HCT in 90% of patients. Twelve patients had mutations in UL97 only;
      the remaining 7 patients had mutations in UL54 only or UL54 and UL97. By 1 year
      from HCT, 11 of 19 (58%) patients with mutations had CMV end-organ disease. CMV
      related mortality in patients with resistance was 42%. CONCLUSIONS: Nine percent
      of CMV R+, CD34+ -selected HCT recipients had resistant CMV by 1 year from HCT.
      Of 19 patients with resistant CMV, 58% had CMV end-organ disease and 42% died of
      CMV. Effective strategies for CMV prevention and restoration of CMV immunity are
      needed for CD34+ -selected HCT.

PMID- 29570239
TI  - Metal-Free Cyclization of ortho-Nitroaryl Ynamides and Ynamines towards
      Spiropseudoindoxyls.
AB  - An efficient metal-free cascade reaction between 1-dibromovinyl-2-nitro
      substituted arenes and secondary amines results in the formation of polycyclic
      pseudoindoxyls in a single step. The reaction mechanism leading to these fused
      ring systems was investigated, and is believed to involve the initial formation
      of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N
      alkenyl-tethered 2-aminoisatogens via a carbene intermediate as demonstrated by
      QTAIM (quantum theory of atoms in molecules) and ELF (electron localization
      function) analysis. A subsequent intramolecular dipolar cycloaddition afforded
      the title compounds.

PMID- 29570240
TI  - Unambiguous identification and characterization of a long-term human metabolite
      of dehydrochloromethyltestosterone.
AB  - In doping control analysis, the characterization of urinary steroid metabolites
      is of high interest for a targeted and long-term detection of prohibited anabolic
      androgenic steroids (AAS). In this work, the structure of a long-term metabolite
      of dehydrochloromethyltestosterone (DHCMT) was elucidated. Altogether, 8 possible
      metabolites with a 17alpha-methyl-17beta-hydroxymethyl - structures were
      synthesized and compared to a major DHCMT long-term metabolite detected in
      reference urine excretion samples. The confirmed structure of the metabolite was
      4alpha-chloro-18-nor-17beta-hydroxymethyl-17alpha-methyl-5alpha-androst-13-en
      3alpha-ol.

PMID- 29570241
TI  - Acute cardiac events in severe community-acquired pneumonia: A multicenter study.
AB  - INTRODUCTION: An increased risk of cardiovascular complications has been defined
      in community-acquired pneumonia (CAP), but limited data is available for patients
      with severe CAP. OBJECTIVE: The aim of the present study was to define the
      prevalence, characteristics, risk factors and impact on mortality of acute
      cardiac events in patients with severe CAP during short and long term. METHOD:
      This investigation was a multicenter, retrospective cohort sudy of patients with
      severe CAP. Cardiac events were defined as cardiac arrhytmia, congestive heart
      failure and myocardial infarction. A logistic regression analysis was performed
      to identify predictors for acute cardiac events and mortality. RESULTS: Of 373
      patients (mean age 68 +/- 16, 61.4% male), 56 (15%) developed a cardiac event (43
      arrhythmia, 11 congestive heart failure and 2 myocardial infarction). Patients
      who developed an acute cardiac event were older, had more severe disease, pleural
      effusion, hypoalbuminemia, hyponatremia and more acidosis. Also, beta-blocker and
      diuretic use were more significant in these patients. In-hospital mortality was
      significantly higher in patients who developed cardiac events (29.6% vs 11%, P <
      .001). According to the logistic regression analysis, haloperidol, vasopressor or
      diuretic use, hypoalbuminemia and age were the predictors for acute cardiac
      events. Acute cardiac events were significantly associated with in-hospital
      mortality (OR 2.1; 95%CI 1.03-4.61, P = .04), but not associated with 90-day
      mortality. CONCLUSION: Our findings demonstrated that acute cardiac events are
      seen in a substantial proportion of patients with severe CAP and their occurence
      significantly associated with in-hospital mortality.

PMID- 29570242
TI  - Germline but not somatic de novo mutations are common in human congenital
      diaphragmatic hernia.
AB  - OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a developmental defect of
      the diaphragm that causes high newborn morbidity and mortality. CDH is considered
      to be a multifactorial disease, with strong evidence implicating genetic factors.
      Although recent studies suggest the biological role of deleterious germline de
      novo variants, the effect of gene variants specific to the diaphragm remains
      unclear, and few single genes have been definitively implicated in human disease.
      METHODS: We performed genome sequencing on 16 individuals with CDH and their
      unaffected parents, including 10 diaphragmatic samples. RESULTS: We did not
      detect damaging somatic mutations in diaphragms, but identified germline
      heterozygous de novo functional mutations of 14 genes in nine patients. Although
      the majority of these genes are not known to be associated with CDH, one patient
      with CDH and cardiac anomalies harbored a frameshift mutation in NR2F2 (aka COUP
      TFII), generating a premature truncation of the protein. This patient also
      carried a missense variant predicted to be damaging in XIRP2 (aka Myomaxin), a
      transcriptional target of MEF2A. Both NR2F2 and MEF2A map to chromosome 15q26,
      where recurring de novo deletions and unbalanced translocations have been
      observed in CDH. CONCLUSIONS: Somatic variants are not common in CDH. To our
      knowledge, this is the second case of a germline de novo frameshift mutation in
      NR2F2 in CDH. Since NR2F2 null mice exhibit a diaphragmatic defect, and XIRP2 is
      implicated in cardiac development, our data suggest the role of these two
      variants in the etiology of CDH, and possibly cardiac anomalies.

PMID- 29570243
TI  - Expedient Construction of the Hexacycle of Franchetine.
AB  - Franchetine, a unique 7,17-seco type of norditerpenoid alkaloid, possesses a
      highly congested polycyclic architecture coupled with nine stereogenic centers.
      Here we present an efficient synthetic approach for the intact hexacyclic
      framework of franchetine from the known tricyle 16 in 20 steps. The synthesis
      features a diastereoselective 6-exo-tet radical cyclization for construction of
      ring A and a unique oxidative Wagner-Meerwein-type rearrangement to realize the
      functionalized [3.2.1] bridging ring CD.

PMID- 29570244
TI  - Metabolic Propensity for Weight Gain Unmasked by Overfeeding.

PMID- 29570246
TI  - The Obesity Paradox: A Misleading Term That Should Be Abandoned.
AB  - The term "obesity paradox" is a figure of speech, not a scientific term. The term
      has no precise definition and has been used to describe numerous observations
      that have little in common other than the finding of an association of obesity
      with a favorable outcome. The terminology has led to misunderstandings among
      researchers and the public alike. It's time for authors and editors to abandon
      the use of this term. Simply labeling counterintuitive findings as the "obesity
      paradox" adds no value. Unexpected findings should not be viewed negatively; such
      findings can lead to new knowledge, better treatments, and scientific advances.

PMID- 29570245
TI  - Nonnutritive Sweeteners in Weight Management and Chronic Disease: A Review.
AB  - OBJECTIVE: The objective of this review was to critically review findings from
      recent studies evaluating the effects of nonnutritive sweeteners (NNSs) on
      metabolism, weight, and obesity-related chronic diseases. Biologic mechanisms
      that may explain NNS effects will also be addressed. METHODS: A comprehensive
      review of the relevant scientific literature was conducted. RESULTS: Most cross
      sectional and prospective cohort studies report positive associations between NNS
      consumption, body weight, and health conditions, including type 2 diabetes,
      cardiovascular disease, and nonalcoholic fatty liver disease. Although findings
      in cellular and rodent models suggest that NNSs have harmful effects on metabolic
      health, most randomized controlled trials in humans demonstrate marginal benefits
      of NNS use on body weight, with little data available on other metabolic
      outcomes. CONCLUSIONS: NNS consumption is associated with higher body weight and
      metabolic disease in observational studies. In contrast, randomized controlled
      trials demonstrate that NNSs may support weight loss, particularly when used
      alongside behavioral weight loss support. Additional long-term, well-controlled
      intervention studies in humans are needed to determine the effects of NNSs on
      weight, adiposity, and chronic disease under free-living conditions.

PMID- 29570247
TI  - Young Adult Cancer: Influence of the Obesity Pandemic.
AB  - OBJECTIVE: The purpose of this article is to review the association of the
      obesity pandemic with appearance of cancers in young adults under age 50 and to
      define potential mechanisms by which obesity may accelerate the development of
      malignancy. METHODS: A comprehensive narrative review was performed to integrate
      preclinical, clinical, and epidemiologic evidence describing the association of
      obesity with cancer in young adults based on a search of PubMed and Google
      databases. RESULTS: Results from more than 100 publications are summarized.
      Although they differ in age groups analyzed and incidence of obesity, sufficient
      data exists to suggest an influence of the obesity pandemic on the increase of
      cancer among young adults. CONCLUSIONS: Cancer in young adults is occurring with
      increasing frequency. Overweight and obesity have become major public health
      issues reaching pandemic proportions. Excess weight is associated with increased
      cancer risk, morbidity, and mortality. Multiple murine models indicate that
      obesity not only increases cancer incidence but also accelerates its development.
      Thus, the possibility exists that overweight and obesity may be contributing to
      the appearance of specific malignancies at younger ages. This prospect, in
      association with the worldwide expansion of obesity, suggests an impending
      explosive increase in obesity-associated cancers in young adults.

PMID- 29570249
TI  - What Do We Need to Do to Get Primary Care Ready to Treat Obesity?

PMID- 29570248
TI  - Free-Living Responses in Energy Balance to Short-Term Overfeeding in Adults
      Differing in Propensity for Obesity.
AB  - OBJECTIVE: Free-living adaptive responses to short-term overfeeding (OF) were
      explored as predictors of longitudinal weight change in adults classified as
      having obesity resistance (OR) or obesity proneness (OP) based on self
      identification and personal/family weight history. METHODS: Adults identified as
      OP (n = 21; BMI: 23.8 +/- 2.5 kg/m2 ) and OR (n = 20; BMI: 20.2 +/- 2.1 kg/m2 )
      completed 3 days of eucaloric feeding (EU; 100% of energy needs) and 3 days of OF
      (140% of energy needs). Following each condition, adaptive responses in physical
      activity (PA), total daily energy expenditure, ad libitum energy intake, and
      energy balance were objectively measured for 3 days in a free-living environment.
      Body mass and composition were measured annually by using dual-energy x-ray
      absorptiometry for 5 years. Adaptive responses to OF were correlated with 5-year
      changes in body mass and composition. RESULTS: Increases in sedentary time
      correlated with longitudinally measured changes in fat mass (r = 0.34, P = 0.04)
      in the cohort taken as a whole. Those with OP reduced their levels of PA
      following OF, whereas those with OR maintained or increased their PA. No other
      variables were found to correlate with weight gain. CONCLUSIONS: Failure to
      decrease sedentary behavior following short-term OF is one mechanism that may be
      contributing to fat mass gain.

PMID- 29570250
TI  - Current Knowledge of Obesity Treatment Guidelines by Health Care Professionals.
AB  - OBJECTIVE: The objective of this study was to assess health care professionals'
      knowledge of evidence-based guidelines for the nonsurgical treatment of obesity.
      METHODS: A nationally representative sample of internists, family practitioners,
      obstetricians/gynecologists, and nurse practitioners completed a web-based survey
      between June 9 and July 1, 2016 (n = 1,506). RESULTS: Only 16% of respondents
      indicated that obesity counseling should be provided approximately twice monthly
      in an individual or group setting for at least 6 months, in accordance with
      United States Preventive Services Task Force and Centers for Medicare and
      Medicaid Services guidelines. Only 15% of respondents identified BMI >= 27 kg/m2
      with an obesity-associated comorbid condition as the appropriate indication to
      prescribe pharmacotherapy for patients. Two-thirds of respondents indicated that
      it is appropriate to continue long-term pharmacotherapy under conditions
      inconsistent with evidence-based guidelines, with nearly one-quarter indicating
      that obesity medications should never be prescribed beyond 3 months regardless of
      weight loss. CONCLUSIONS: These findings suggest that provider understanding of
      appropriate clinical care for obesity is inconsistent with evidence-based
      recommendations. As coverage for behavioral counseling services and
      pharmacotherapy expands, it is imperative that health care professionals
      understand how to effectively leverage these treatment modalities to optimize
      health outcomes for patients with obesity.

PMID- 29570251
TI  - Tumor-derived exosomes modulate T cell function through transfer of RNA.
AB  - Tumor cells can develop a variety of mechanisms to evade and subvert the immune
      system for their survival. Bland et al., in this edition of The FEBS Journal,
      make the novel finding that the tumor line B16F0 can deliver mRNA/miRNA loaded
      exosomes to cytotoxic T lymphocytes and alter their metabolic function and
      interferon gamma production.

PMID- 29570254
TI  - Diagnostic accuracy of multiparametric magnetic resonance imaging in detecting
      extracapsular extension in intermediate and high - risk prostate cancer.
AB  - OBJECTIVES: To evaluate the diagnostic performance of preoperative
      multiparametric magnetic resonance imaging (mp-MRI) as a predictor of
      extracapsular extension (ECE) and unfavorable Gleason score (GS) in patients with
      intermediate and high-risk prostate cancer (PCa). MATERIALS AND METHODS: Patients
      with clinically localized PCa who underwent radical prostatectomy (RP) and had
      preoperative mp-MRI between May-2011 and December-2013. Mp-MRI was evaluated
      according to the European Society of Urogenital Radiology MRI prostate guidelines
      by two different readers. Histopathological RP results were the standard
      reference. RESULTS: 79 patients were included; mean age was 61 and median
      preoperative prostate-specific antigen (PSA) 7.0. On MRI, 28% patients had ECE
      evidenced in the mp-MRI, 5% seminal vesicle invasion (SVI) and 4% lymph node
      involvement (LNI). At RP, 39.2% had ECE, 26.6% SVI and 12.8% LNI. Sensitivity,
      specificity, accuracy, positive predictive value (PPV), and negative predictive
      value (NPV) of mp-MRI for ECE were 54.9%, 90.9%, 76%, 81% and 74.1% respectively;
      for SVI values were 19.1%, 100%, 77.3%, 100% and 76.1% respectively and for LNI
      20%, 98.4%, 86.7%, 66.7% and 88.7%. CONCLUSIONS: Major surgical decisions are
      made with digital rectal exam (DRE) and ultrasound studies before the use of Mp
      MRI. This imaging study contributes to rule out gross extraprostatic extension
      (ECE, SVI, LNI) without competing with pathological studies. The specificity and
      NPV are reasonable to decide surgical approach. A highly experienced radiology
      team is needed to provide accurate estimations of tumor extension and
      aggressiveness.

PMID- 29570255
TI  - BCG instillations can mimic prostate cancer on multiparametric MRI.

PMID- 29570256
TI  - Laparoscopic management of paraganglioma in a pregnant woman: a case report.
AB  - INTRODUCTION: Paraganglioma is an extremely rare catecholamine-producing tumor
      during pregnancy. Paraganglioma carries high risks of fetal and maternal
      mortality during pregnancy. We report a pregnant woman with paraganglioma in the
      second trimester. CASE DESCRIPTION: A 24-year-old pregnant woman presented with
      severe hypertension in the 17th week of gestation. Hormonal examination and
      Magnetic Resonance Imaging (MRI) confirmed the diagnosis of extra adrenal
      pheochromocytoma (paraganglioma). She underwent laparoscopic tumor excision
      successfully. CONCLUSIONS: A high index of suspicion is needed to diagnose
      paraganglioma in a pregnant patient with hypertension. Laparoscopic tumor removal
      for paraganglioma seems to be a feasible and safe procedure during pregnancy.

PMID- 29570257
TI  - Retroperitoneoscopic resection of retroperitoneal nonadrenal ganglioneuromas: our
      technique and clinical outcomes.
AB  - OBJECTIVE: To report our experience of retroperitoneoscopic technique in semi
      lateral decubitus position for the retroperitoneal nonadrenal ganglioneuromas in
      18 patients, and to evaluate its clinical outcomes. MATERIALS AND METHODS: From
      January 2012 to May 2016, 18 patients with retroperitoneal nonadrenal
      ganglioneuromas underwent retroperitoneoscopic resection. With the patients in
      semi-lateral decubitus position, a 4-port retroperitoneal approach was used. Data
      were collected on the tumor size, tumor location, perioperative outcomes,
      pathology, and lastknown disease status. We reviewed the operative videos to
      identify surgical tips and tricks. RESULTS: All procedures were carried out
      successfully without converting to open surgery. The tumors had an average size
      of 5.2cm. The mean operative time was 86.5 min, with a mean estimated blood loss
      of 85.4mL. There were three patients suffering from intraoperative complications.
      Postoperatively, all patients achieved an uneventful recovery; the mean
      postoperative hospital stay was 5.5 days. The postoperative pathology revealed to
      be retroperitoneal ganglioneuromas. With a mean follow-up of 39.5 months, all
      patients were recurrence free. The review of the operative videos revealed
      several tips and tricks, including keeping peritoneum and posterior Gerota fascia
      intact to provide a favorable operative exposure of tumors, and placing the
      harmonic scalpel through different ports during tumor dissection. CONCLUSIONS:
      With the patient in semi-lateral decubitus position and a 4-port retroperitoneal
      approach, retroperitoneoscopic resection of retroperitoneal nonadrenal
      ganglioneuroma is a feasible, effective, and safe procedure. This approach has
      distinct advantages including direct access to the tumor, optimal exposure of
      tumor and less intraperitoneal interference.

PMID- 29570258
TI  - Re: Gaseous bladder tamponade secondary to emphysematous cystitis.

PMID- 29570259
TI  - Prognostic significance of the dynamic changes of systemic inflammatory response
      in metastatic renal cell carcinoma.
AB  - PURPOSE: To elucidate the prognostic value of systemic inflammatory response in
      patients with metastatic renal cell carcinoma (mRCC) who are treated with
      sunitinib, we evaluated the prognostic role of C-reactive protein (CRP) kinetics.
      This study also compared prognostic models containing CRP kinetics and neutrophil
      to-lymphocyte ratio (NLR) kinetics. MATERIALS AND METHODS: A consecutive cohort
      of 94 patients with mRCC who were treated with sunitinib was retrospectively
      included from Fudan University Shanghai Cancer Center. According to dynamic
      changes in CRP and the NLR, patients were divided into three groups for analysis
      of CRP and NLR kinetics. The associations between survival and potential
      prognostic factors were assessed. The incremental value of prognostication was
      evaluated. RESULTS: A significant difference (P<0.001) in overall survival (OS)
      was observed among the three groups of CRP kinetics. The median OS of the non
      elevated group was nearly 1.3-fold longer than that of the normalized group (33.0
      vs. 26.3 months), and two times longer than that of the non-normalized group
      (33.0 vs. 14.0 months). Multivariate analysis showed that CRP and NLR kinetics
      were independent prognostic indicators. The model containing CRP kinetics had a
      better predictive accuracy than that with NLR kinetics, which was supported by
      the C-index (0.731 vs. 0.684) and the likelihood ratio chi2 test (79.9% vs.
      44.9%). CONCLUSION: Our study suggests that dynamic changes in CRP can better
      predict survival in patients with mRCC who are treated with sunitinib. Routine
      assessment of CRP before and after targeted therapy would help identify patients
      at risk of a poor outcome.

PMID- 29570260
TI  - The history of varicocele: from antiquity to the modern ERA.
AB  - Men have most likely been affected by varicocele since the assumption of the
      upright position. In De Medicina, written during the first century AD, Celsus
      credits the Greeks with the first description of a varicocele, and he recorded
      his own acute observation: "The veins are swollen and twisted over the testicle,
      which becomes smaller". Celsus himself is credited with the distinction between
      varicocele (dilation of surface veins) and "cirsocele" (dilation of deep veins).
      There has been a long history of treatment attempts and failures, some of which
      are remarkably strange, that have sometimes culminated in tragedy, as in the case
      of French professor Jacques-Mathieu Delpech (1772- 1832). Although some questions
      regarding the etiopathology and treatment of varicocele remain unanswered, a
      succession of more or less conservative attempts involving all medical cultures
      has been performed throughout history. The report by W.S. Tulloch in 1952 brought
      varicocele into the era of modern evidence-based medicine, and varicocele surgery
      finally progressed beyond the aim of merely relieving scrotal pain and swelling.
      From 1970 to 2000, varicocelectomies gained worldwide attention for the treatment
      of male infertility. Several innovative procedures to correct varicoceles began
      to appear in the world's literature as interventional radiology, microsurgery,
      laparoscopy, and robotics, while comprehensive review articles were also
      published on the subject of varicocelectomies. Microsurgery is nowadays used
      worldwide and it can be considered to be the gold standard for correcting
      infertility linked to varicocele.

PMID- 29570261
TI  - Objective measurements of the penile angulation are significantly different than
      self-estimated magnitude among patients with penile curvature.
AB  - INTRODUCTION: The study was aimed to assess the presence of actual differences
      between the objective and the perceived magnitude of a curvature between patients
      affected by Peyronie's disease (PD) and congenital penile curvature (CPC).
      MATERIALS AND METHODS: Wee analysed a cohort of 88 consecutive patients seeking
      medical help for either CPC or PD. All patients were invited to provide a self
      made drawing of their penis in erection in order to obtain self-provided
      description of the deformity. An objective measurement of the deformity was also
      performed drawing two intersecting lines through the center of the distal and
      proximal straight section of the penile shaft. RESULTS: Our findings showed
      significant differences between patient self-estimation and the objective
      measurements of the penile angulation performed by trained experts, with only 32%
      of patients correctly assessing their own curvature. Overall, patients tended to
      overestimate (56%) their degree of curvature, but the results are different in
      patients with PD than those with CPC. In the 60 men (68%) who did not accurately
      assess their curvature, PD patients generally overestimated their curvature
      versus CPC patients (67% vs 16%). On the contrary CPC patients underestimated
      their curvature compared to PD (42% vs. 4%). CONCLUSION: In order to improve
      patients' satisfaction rates, the surgeon needs to take into consideration the
      patient's perception of the deformity when planning the type of surgical
      correction.

PMID- 29570262
TI  - Polygamy, sexual behavior in a population under risk for prostate cancer
      diagnostic: an observational study from the Black Sea Region in Turkey.
AB  - AIM: Although prostate cancer (PCa) is the most common cancer type in men, a
      replaceable risk factor has not yet been established. In our study, we assessed
      the relationship between the number of sexual partners, age of first sexual
      experience and age of first masturbation and prostate cancer incidence. MATERIALS
      AND METHODS: In Ordu University Department of Urology between January 2013 and
      September 2016, in PSA elevation and rectal examination, patients with prostate
      biopsy were evaluated due to nodule palpation in the prostate. At younger ages
      and at present, their first masturbation ages, first sexual debut ages, and total
      sexual partner numbers were recorded. The correlation between the obtained data
      and PCa frequency was evaluated. RESULTS: The study included 146 patients with
      PCa identified on biopsy and 171 patients with benign biopsy results who answered
      the questions. 66.7% of the ones whose biopsy results were benign and 40.6% of
      cancer suspects had only one sexual partner. The median number of sexual partners
      was 1+/-4 (1-100) in the benign group and 2+/-6 (1-500) in the malignant group
      (p=0.039). There was a negative correlation between age of first sexual debut and
      number of partners (r: -0,479; p<0.001). CONCLUSION: In our study, it appears
      that there may be an association between the number of sexual partners and
      prostate cancer in the patient group with PSA level above 4ng/mL. Avoidance of
      sexual promiscuity or participation in protected sex may be beneficial to protect
      against prostate cancer.

PMID- 29570263
TI  - Direct Writing and Characterization of Three-Dimensional Conducting Polymer PEDOT
      Arrays.
AB  - Direct writing is an effective and versatile technique for three-dimensional (3D)
      fabrication of conducting polymer (CP) structures. It is precisely localized and
      highly controllable, thus providing great opportunities for incorporating CPs
      into microelectronic array devices. Herein we demonstrate 3D writing and
      characterization of poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate
      (PEDOT:PSS) pillars in an array format, by using an in-house-constructed variant
      of scanning ion conductance microscopy (SICM). CP pillars with different aspect
      ratios were successfully fabricated by optimizing the writing parameters: pulling
      speed, pulling time, concentration of the polymer solution, and the micropipette
      tip diameter. Especially, super high aspect ratio pillars of around 7 MUm in
      diameter and 5000 MUm in height were fabricated, indicating a good capability of
      this direct writing technique. Additions of an organic solvent and a cross
      linking agent contribute to a significantly enhanced water stability of the
      pillars, critical if the arrays were to be used in biologically relevant
      applications. Surface morphologies and structural analysis of CP pillars were
      characterized by scanning electron microscopy and Raman spectroscopy,
      respectively. Electrochemical properties of the individual pillars of different
      heights were examined by cyclic voltammetry using a double-barrel micropipette as
      an electrochemical cell. Exceptional mechanical properties of the pillars, such
      as high flexibility and robustness, were observed when bent by applying a force.
      The 3D pillar arrays are expected to provide versatile substrates for
      functionalized and integrated biological sensing and electrically addressable
      array devices.

PMID- 29570264
TI  - Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological
      Responses to the Locally Produced Nitric Oxide.
AB  - Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a
      wide spectrum of physiological activities. In this work, we developed an
      enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic
      surface coatings. Multilayered polyelectrolyte films were optimized as host
      compartments for the immobilized beta-galactosidase (beta-Gal) enzyme through a
      screen of eight polycations and eight polyanions. The lead composition was used
      to achieve localized production of NO through the addition of beta-Gal-NONOate, a
      prodrug that releases NO following enzymatic bioconversion. The resulting
      coatings afforded physiologically relevant flux of NO matching that of the
      healthy human endothelium. The antiproliferative effect due to the synthesized NO
      in cell culture was site-specific: within a multiwell dish with freely shared
      media and nutrients, a 10-fold inhibition of cell growth was achieved on top of
      the biocatalytic coatings compared to the immediately adjacent enzyme-free
      microwells. The physiological effect of NO produced via the enzyme prodrug
      therapy was validated ex vivo in isolated arteries through the measurement of
      vasodilation. Biocatalytic coatings were deposited on wires produced using alloys
      used in clinical practice and successfully mediated a NONOate concentration
      dependent vasodilation in the small arteries of rats. The results of this study
      present an exciting opportunity to manufacture implantable biomaterials with
      physiological responses controlled to the desired level for personalized
      treatment.

PMID- 29570265
TI  - Integrated Analysis of Exosomal Protein Biomarkers on Alternating Current
      Electrokinetic Chips Enables Rapid Detection of Pancreatic Cancer in Patient
      Blood.
AB  - Pancreatic ductal adenocarcinoma (PDAC) typically has nonspecific symptoms and is
      often found too late to treat. Because diagnosis of PDAC involves complex,
      invasive, and expensive procedures, screening populations at increased risk will
      depend on developing rapid, sensitive, specific, and cost-effective tests.
      Exosomes, which are nanoscale vesicles shed into blood from tumors, have come
      into focus as valuable entities for noninvasive liquid biopsy diagnostics.
      However, rapid capture and analysis of exosomes with their protein and other
      biomarkers have proven difficult. Here, we present a simple method integrating
      capture and analysis of exosomes and other extracellular vesicles directly from
      whole blood, plasma, or serum onto an AC electrokinetic microarray chip. In this
      process, no pretreatment or dilution of sample is required, nor is it necessary
      to use capture antibodies or other affinity techniques. Subsequent on-chip
      immunofluorescence analysis permits specific identification and quantification of
      target biomarkers within as little as 30 min total time. In this initial
      validation study, the biomarkers glypican-1 and CD63 were found to reflect the
      presence of PDAC and thus were used to develop a bivariate model for detecting
      PDAC. Twenty PDAC patient samples could be distinguished from 11 healthy subjects
      with 99% sensitivity and 82% specificity. In a smaller group of colon cancer
      patient samples, elevated glypican-1 was observed for metastatic but not for
      nonmetastatic disease. The speed and simplicity of ACE exosome capture and on
      chip biomarker detection, combined with the ability to use whole blood, will
      enable seamless "sample-to-answer" liquid biopsy screening and improve early
      stage cancer diagnostics.

PMID- 29570266
TI  - Enhancing Antibody Serodiagnosis Using a Controlled Peptide Coimmobilization
      Strategy.
AB  - Antigen immunoreactivity is often determined by surface regions defined by the 3D
      juxtapositions of amino acids stretches that are not continuous in the linear
      sequence. As such, mimicking an antigen immunoreactivity by means of putative
      linear peptide epitopes for diagnostic purposes is not trivial. Here we present a
      straightforward and robust method to extend the reach of immune-diagnostic probes
      design by copresenting peptides belonging to the same antigenic surface. In this
      case study focused on a computationally predicted Zika virus NS1 protein putative
      antigenic region, we reached a diagnostic confidence by the oriented and
      spatially controlled coimmobilization of peptide sequences found adjacent within
      the protein fold, that cooperatively interacted to provide enhanced
      immunoreactivity with respect to single linear epitopes. Through our method, we
      were able to differentiate Zika infected individuals from healthy controls.
      Remarkably, our strategy fits well with the requirements to build high-throughput
      screening platforms of linear and mixed peptide libraries, and it could possibly
      facilitate the rapid identification of conformational immunoreactive regions.

PMID- 29570268
TI  - A Fluorescent Probe for Stimulated Emission Depletion Super-Resolution Imaging of
      Vicinal-Dithiol-Proteins on Mitochondrial Membrane.
AB  - Realizing the significant roles of vicinal-dithiol proteins (VDPs) in maintaining
      the cellular redox homeostasis and their implication in many diseases, we
      synthesized a smart arsenate based fluorescent probe 1 which can preferentially
      target the mitochondrial membrane-bound vicinal dithiol proteins (VDPs),
      especially voltage-dependent anion channel (VDAC2). The probe targetability was
      demonstrated by in vitro studies such as colocalization, stimulated emission
      depletion (STED) super-resolution imaging, proteomic MS/MS analysis, and Western
      blot analysis. The probe represents a rare example of fluorescence labeling of
      mitochondrial membrane-bound VDPs and can provide a new way to construct VDPs
      specific fluorescent probes to gain deeper understanding of their roles in
      mitochondrial-related disorders.

PMID- 29570269
TI  - Shear Adhesion of Tapered Nanopillar Arrays.
AB  - Tapered nanopillars with various cross sections, including cone-shaped, stepwise,
      and pencil-like structures (300 nm in diameter at the base of the pillars and 1.1
      MUm in height), are prepared from epoxy resin templated by nanoporous anodic
      aluminum oxide (AAO) membranes. The effect of pillar geometry on the shear
      adhesion behavior of these nanopillar arrays is investigated via sliding
      experiments in a nanoindentation system. In a previous study of arrays with the
      same geometry, it was shown that cone-shaped nanopillars exhibit the highest
      adhesion under normal loading while stepwise and pencil-like nanopillars exhibit
      lower normal adhesion strength due to significant deformation of the pillars that
      occurs with increasing indentation depth. Contrary to the previous studies, here,
      we show that pencil-like nanopillars exhibit the highest shear adhesion strength
      at all indentation depths among three types of nanopillar arrays and that the
      shear adhesion increases with greater indentation depth due to the higher bending
      stiffness and closer packing of the pencil-like nanopillar array. Finite element
      simulations are used to elucidate the deformation of the pillars during the
      sliding experiments and agree with the nanoindentation-based sliding
      measurements. The experiments and finite element simulations together demonstrate
      that the shape of the nanopillars plays a key role in shear adhesion and that the
      mechanism is quite different from that of adhesion under normal loading.

PMID- 29570270
TI  - Cascade Amplification-Mediated In Situ Hot-Spot Assembly for MicroRNA Detection
      and Molecular Logic Gate Operations.
AB  - MicroRNAs (miRNAs) play important roles in many biological processes and are
      associated with various diseases, especially cancers. Combination of
      technological developments such as nanomaterials, functional enzyme-mediated
      reactions, and DNA nanotechnology holds great potential for high-performance
      detection of miRNAs in molecular diagnostic systems. In this work, we have
      fabricated a cascade signal amplification platform through integrating duplex
      specific nuclease (DSN)-assisted target recycling with catalytic hairpin assembly
      (CHA) reaction for the detection of microRNA-141 (miR-141). The target recycling
      process driven by DSN results in highly amplified translation of target miRNA to
      single-stranded connector DNA fragments. The CHA reaction is further initiated by
      connector DNAs using hairpin-modified gold nanoparticles (HP-AuNPs) as the
      sensing unit, leading to the formation of AuNP network architecture on the
      electrode for electrochemical and photoelectrochemical detection of miR-141 in
      signal-on and signal-off modes, respectively. The developed electrochemical
      biosensor exhibits a detection limit down to 25.1 aM miR-141 (60 copies in 4 MUL
      sample) and excellent selectivity to discriminate a single base-mismatched
      sequence and other miRNAs. This assay is also applied to the determination of miR
      141 in total RNAs extracted from human breast cancer cells (MDA-MB-231),
      confirming the applicability of this method for absolute quantification of
      specific miRNAs in real-world samples. Furthermore, two-input AND and INHIBIT
      (INH) logic gates are constructed to detect miRNAs. In particular, the AND gate
      achieves cell-specific gate activation based on expression profiles of miR-141
      and microRNA-21 (miR-21). Therefore, our proposed cascade amplification platform
      has great potential applications in miRNA-related clinical diagnostics and
      biochemical research.

PMID- 29570267
TI  - Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying
      Sub-Nanometer Mechanical Motion.
AB  - Action potentials in neurons have been studied traditionally by intracellular
      electrophysiological recordings and more recently by the fluorescence detection
      methods. Here we describe a label-free optical imaging method that can measure
      mechanical motion in single cells with a sub-nanometer detection limit. Using the
      method, we have observed sub-nanometer mechanical motion accompanying the action
      potential in single mammalian neurons by averaging the repeated action potential
      spikes. The shape and width of the transient displacement are similar to those of
      the electrically recorded action potential, but the amplitude varies from neuron
      to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm.
      The work indicates that action potentials may be studied noninvasively in single
      mammalian neurons by label-free imaging of the accompanying sub-nanometer
      mechanical motion.

PMID- 29570271
TI  - Establishment of Novel Biosynthetic Pathways for the Production of Salicyl
      Alcohol and Gentisyl Alcohol in Engineered Escherichia coli.
AB  - Salicyl alcohol and gentisyl alcohol are two important phenolic alcohols that
      possess significant biological activities and pharmaceutical properties. Here, we
      report establishment of novel biosynthetic pathways for microbial production of
      salicyl alcohol and gentisyl alcohol from renewable feedstocks. We first examined
      the promiscuity of the carboxylic acid reductase CAR toward salicylic acid and
      2,5-DHBA, which enabled efficient synthesis of salicyl alcohol and gentisyl
      alcohol. Then, we employed a novel salicylic acid 5-hydroxylase to achieve 2,5
      DHBA production from salicylic acid. After that, the de novo biosynthetic
      pathways were assembled and optimized by programming the carbon flux into the
      shikimate pathway. The final titers of salicyl alcohol and gentisyl alcohol
      reached to 594.4 mg/L and 30.1 mg/L, respectively. To our knowledge, this work
      achieved microbial production of salicyl alcohol and gentisyl alcohol for the
      first time. Our present study also demonstrated application of enzyme promiscuity
      to establish non-natural biosynthetic pathways for the production of high-value
      compounds.

PMID- 29570272
TI  - Comprehensive Biochemical and Biophysical Characterization of Hemoglobin-Based
      Oxygen Carrier Therapeutics: All HBOCs Are Not Created Equally.
AB  - The development of hemoglobin (Hb)-based oxygen carriers (HBOCs) has been
      hampered because of safety concerns in humans. Chemical and/or genetic
      modifications of the Hb introduce varied structural and conformational constraint
      on the molecule that resulted in proteins with diverse allosteric responses,
      nitrosative and oxidative side reactions. Here, we present for the first time a
      comprehensive biochemical and biophysical comparison of human, bovine, and
      genetically engineered HBOCs that have been tested in humans. We evaluate oxygen
      equilibrium and ligand binding kinetics under different experimental conditions
      as well as their autoxidation kinetics, redox reactions, and heme release. We
      determined the effects of HBOCs on cellular redox states and mitochondrial
      respiration. Taken together, these experiments provide a better understanding of
      the relationship between the structure-function and oxidative reactivity of these
      proteins. One can therefore select independently among these diverse properties
      to engineer a safe and effective HBOC with improved biochemical/biophysical
      characteristics.

PMID- 29570273
TI  - Photoinduced Regeneration of an Aptamer-Based Electrochemical Sensor for
      Sensitively Detecting Adenosine Triphosphate.
AB  - Electrochemical aptasensors generally include three elements, that is,
      recognition element, signal-transformation element, and regeneration element. In
      this study, a new adenosine triphosphate (ATP) aptasensor is developed by
      combining three elements into one DNA oligonucleotide chain. In the DNA
      oligonucleotide chain, DNA aptamer is used as the recognition element, ferrocene
      group attached at the 3'-end of the aptamer is used as the signal-transformation
      element, and azobenzene moiety embedded into the DNA chain is used as the
      regeneration element. In addition to the similar analytical properties with the
      traditional ones, the aptasensor developed here is easily regenerated with UV
      light irradiation. The current response recorded on the aptasensor increases with
      increasing the concentration of ATP in the incubation solution and is linear with
      the logarithm of ATP concentration in the range from 1 nM to 100 MUM. The limit
      of detection is 0.5 nM (S/N = 3). The basal level of ATP in the rat brain cortex
      microdialysate is determined to be 21.33 +/- 4.1 nM ( n = 3). After being
      challenged with ATP, the aptasensor could be readily regenerated by UV-light
      irradiation for more than seven cycles. The regeneration of the aptasensor is
      proposed to be regulated by conversing azobenzene from its trans to cis form
      under UV irradiation.

PMID- 29570274
TI  - Oxygen Species on Nitrogen-Doped Carbon Nanosheets as Efficient Active Sites for
      Multiple Electrocatalysis.
AB  - Designing and synthesizing nanomaterials with high coverages of active sites is
      one of the most-pivotal factors in the construction of state-of-the-art
      electrocatalysts with high performance. Herein, we proposed a facile in situ
      templated method for the fabrication of oxygen-species-modified nitrogen-doped
      carbon nanosheets (O-N-CNs). The epoxy oxygen and ketene oxygen combined with
      graphitic-nitrogen defects in O-N-CNs gave more active sites for the oxygen
      reduction reaction (ORR) and the oxygen-evolution reaction (OER), as proven via
      theoretical and experimental results, while the carbonyl-oxygen and epoxy-oxygen
      species showed more efficient electrocatalytic activity for the hydrogen
      evolution reaction (HER). Hence, the O-N-CNs showed highly active
      electrocatalytic performance toward ORR, OER, and HER. More importantly, the
      superior multifunctional electrocatalytic activity of O-N-CNs allowed their use
      in the construction of Zn-air batteries to power the corresponding water
      splitting cells. This work can offer an understanding of underlying mechanisms of
      oxygen species on N-doped carbon materials toward multiple electrocatalysis and
      facilitate the engineering of electrocatalysts for energy-storage and -conversion
      devices.

PMID- 29570275
TI  - Structural Characterization of a Heparan Sulfate Pentamer Interacting with LAR
      Ig1-2.
AB  - Leukocyte common antigen-related (LAR) protein is one of the type IIa receptor
      protein tyrosine phosphatases (RPTPs) that are important for signal transduction
      in biological processes, including axon growth and regeneration.
      Glycosaminoglycan chains, including heparan sulfate (HS) and chondroitin sulfate
      (CS), act as ligands that regulate LAR signaling. Here, we report the structural
      characterization of the first two immunoglobulin domains (Ig1-2) of LAR
      interacting with an HS pentasaccharide (GlcNS6S-GlcA-GlcNS3,6S-IdoA2S-GlcNS6S
      OME, fondaparinux) using multiple solution-based NMR methods. In the course of
      the study, we extended an assignment strategy useful for sparsely labeled
      proteins expressed in mammalian cell culture supplemented with a single type of
      isotopically enriched amino acid ([15N]-Lys in this case) by including
      paramagnetic perturbations to NMR resonances. The folded two-domain structure for
      LAR-Ig1-2 seen in previous crystal structures has been validated in solution
      using residual dipolar coupling data, and a combination of chemical shift
      perturbation on titration of LAR-Ig1-2 with fondaparinux, saturation transfer
      difference (STD) spectra, and transferred nuclear Overhauser effects (trNOEs)
      have been employed in the docking program HADDOCK to generate models for the LAR
      fondaparinux complex. These models are further analyzed by postprocessing
      energetic analysis to identify key binding interactions. In addition to providing
      insight into the ligand interaction mechanisms of type IIa RPTPs and the origin
      of opposing effects of CS and HS ligands, these results may assist in future
      design of therapeutic compounds for nervous system repair.

PMID- 29570276
TI  - Surprising Sequence Effects on GU Closure of Symmetric 2 * 2 Nucleotide RNA
      Internal Loops.
AB  - GU base pairs are important RNA structural motifs and often close loops. Accurate
      prediction of RNA structures relies upon understanding the interactions
      determining structure. The thermodynamics of some 2 * 2 nucleotide internal loops
      closed by GU pairs are not well understood. Here, several self-complementary
      oligonucleotide sequences expected to form duplexes with 2 * 2 nucleotide
      internal loops closed by GU pairs were investigated. Surprisingly, nuclear
      magnetic resonance revealed that many of the sequences exist in equilibrium
      between hairpin and duplex conformations. This equilibrium is not observed with
      loops closed by Watson-Crick pairs. To measure the thermodynamics of some 2 * 2
      nucleotide internal loops closed by GU pairs, non-self-complementary sequences
      that preclude formation of hairpins were designed. The measured thermodynamics
      indicate that some internal loops closed by GU pairs are unusually unstable. This
      instability accounts for the observed equilibria between duplex and hairpin
      conformations. Moreover, it suggests that future three-dimensional structures of
      loops closed by GU pairs may reveal interactions that unexpectedly destabilize
      folding.

PMID- 29570278
TI  - Peptide-Based Sandwich Immunoassay for the Quantification of the Membrane
      Transporter Multidrug Resistance Protein 1.
AB  - Multitransmembrane proteins are notoriously difficult to analyze. To date, rapid,
      and cost-efficient detection methods are lacking and only mass spectrometry-based
      systems allow reliable quantification of these proteins. Here, we present a novel
      type of sandwich immunoassay that is capable of sensitively detecting multidrug
      resistance protein 1 (MDR1), a prototypic 12-transmembrane-domains transporter.
      In a first assay step, complex samples are enzymatically fragmented into peptides
      as routinely done for mass spectrometry. A proteotypic peptide derived from MDR1
      was chosen and antibodies targeting this peptide were used to build a sandwich
      immunoassay. Validation of the optimized assay showed good sensitivity,
      reproducibility and it allowed reliable quantification of MDR1; cross-validation
      by mass spectrometry demonstrated the applicability for routine analyses in
      clinical and pharmaceutical research. MDR1 was quantified in primary human renal
      cell carcinoma and corresponding normal tissue and down-regulation or expression
      loss was found in tumor tissue corroborating its importance in drug resistance
      and efficacy.

PMID- 29570279
TI  - Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections: Promises
      and Perils.
AB  - Despite their high global incidence, sexually transmitted infections (STIs)
      remain a neglected area of research. Increased rates of STIs have been reported
      in particular among men who have sex with men (MSM) probably because of the
      advances in the treatment and prophylaxis of human immunodeficiency virus (HIV)
      infection with a decrease in condom use. A recent report among MSM showed that
      the use of postexposure prophylaxis with doxycycline could dramatically reduce
      the incidence of chlamydia and syphilis but not of gonorrhea. The long-term
      consequences of this strategy are yet unknown, especially the risk of selection
      and dissemination of syphilis and chlamydia strains with doxycycline resistance,
      which has not been reported yet.

PMID- 29570277
TI  - Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for
      Arbitrary Localization of Magnetic Hyperthermia Therapy.
AB  - Image-guided treatment of cancer enables physicians to localize and treat tumors
      with great precision. Here, we present in vivo results showing that an emerging
      imaging modality, magnetic particle imaging (MPI), can be combined with magnetic
      hyperthermia into an image-guided theranostic platform. MPI is a noninvasive 3D
      tomographic imaging method with high sensitivity and contrast, zero ionizing
      radiation, and is linearly quantitative at any depth with no view limitations.
      The same superparamagnetic iron oxide nanoparticle (SPIONs) tracers imaged in MPI
      can also be excited to generate heat for magnetic hyperthermia. In this study, we
      demonstrate a theranostic platform, with quantitative MPI image guidance for
      treatment planning and use of the MPI gradients for spatial localization of
      magnetic hyperthermia to arbitrarily selected regions. This addresses a key
      challenge of conventional magnetic hyperthermia-SPIONs delivered systemically
      accumulate in off-target organs ( e.g., liver and spleen), and difficulty in
      localizing hyperthermia results in collateral heat damage to these organs. Using
      a MPI magnetic hyperthermia workflow, we demonstrate image-guided spatial
      localization of hyperthermia to the tumor while minimizing collateral damage to
      the nearby liver (1-2 cm distance). Localization of thermal damage and therapy
      was validated with luciferase activity and histological assessment. Apart from
      localizing thermal therapy, the technique presented here can also be extended to
      localize actuation of drug release and other biomechanical-based therapies. With
      high contrast and high sensitivity imaging combined with precise control and
      localization of the actuated therapy, MPI is a powerful platform for magnetic
      based theranostics.

PMID- 29570280
TI  - Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1
      Entry and Cell to Cell Fusion.
AB  - Cell-to-cell transmission is the most effective pathway for the spread of human
      immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion
      proteins on their surface as a consequence of HIV-1 replicative cycle that
      interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor
      leading to the formation of giant multinucleated cells known as syncytia. Our
      group previously described the potent activity of dendrimers against CCR5-tropic
      viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the
      context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation
      remains still unknown. These dendrimers showed a suitable biocompatibility in all
      cell lines studied and our results demonstrated that anionic carbosilane
      dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1
      infection, as well as syncytia formation, in a dose dependent manner. We also
      demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in
      HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico
      models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and
      demonstrated its potential use for a treatment.

PMID- 29570281
TI  - Porous Anionic Uranyl-Organic Networks for Highly Efficient Cs+ Adsorption and
      Investigation of the Mechanism.
AB  - Exploitation of new materials for the removal of long-lived and highly
      radioactive actinides and their fission products produced in the nuclear fuel
      cycle is crucial for radionuclide management. Here, two rare porous anionic
      uranyl-organic frameworks (UOFs) have been successfully synthesized by a
      judicious combination of the tetratopic carboxylate ligand 1,3,6,8-tetrakis( p
      benzoic acid)pyrene (H4TBAPy) and D3 h-symmetrical triangular [UO2(COO)3]-. The
      resulting two compounds exhibit different architectures, albeit with similar
      coordination modes. Of interest is that they have excellent adsorption
      performance on Cs+ from aqueous solution. The high removal efficency would make
      them promising in applications of radioactive waste management. Notably, the
      framework of compound 2, [(CH3)2NH2]4[(UO2)4(TBAPy)3].22DMF.37H2O is sufficiently
      robust to allow the accessibility of intriguing single crystals of a Cs+-adsorbed
      derivative, which helps to elucidate the adsorption mechanism. The structural,
      bonding, and spectroscopic properties of the above compounds are examined using
      relativistic density functional theory (DFT). It is found that the adsorption
      toward cesium on UOFs is energetically favored, which features largely ionic
      bonds and is dominated by electrostatic attraction.

PMID- 29570282
TI  - Effect of Intercalated Water on Potassium Ion Transport through Kv1.2 Channels
      Studied via On-the-Fly Free-Energy Parametrization.
AB  - We introduce a two-dimensional version of the method called on-the-fly free
      energy parametrization (OTFP) to reconstruct free-energy surfaces using Molecular
      Dynamics simulations, which we name OTFP-2D. We first test the new method by
      reconstructing the well-known dihedral angles free energy surface of solvated
      alanine dipeptide. Then, we use it to investigate the process of K+ ions
      translocation inside the Kv1.2 channel. By comparing a series of two-dimensional
      free energy surfaces for ion movement calculated with different conditions on the
      intercalated water molecules, we first recapitulate the widely accepted knock-on
      mechanism for ion translocation and then confirm that permeation occurs with
      water molecules alternated among the ions, in accordance with the latest
      experimental findings. From a methodological standpoint, our new OTFP-2D
      algorithm demonstrates the excellent sampling acceleration of temperature
      accelerated molecular dynamics and the ability to efficiently compute 2D free
      energy surfaces. It will therefore be useful in large variety complex
      biomacromolecular simulations.

PMID- 29570283
TI  - Quantum Yields, Surface Quenching, and Passivation Efficiency for Ultrasmall
      Core/Shell Upconverting Nanoparticles.
AB  - We synthesized and characterized a set of ultrasmall hexagonal-phase NaGdF4: 20%
      Yb3+, 2% Er3+ upconversion nanoparticles with core diameters of 3.7 +/- 0.5 nm.
      In order to assess passivation effects and the influence of possible core-shell
      intermixing and to identify optimum particle structures for combined imaging in
      the visible and near-infrared (vis-NIR: 410-850 nm) and short-wave infrared
      (SWIR: 1520 nm), NaYF4 shells of varying thicknesses (monolayer to 10 nm) were
      introduced and the influence of this parameter on the upconversion and
      downshifting photoluminescence of these particles was studied at different
      excitation power densities. This included excitation power-dependent emission
      spectra, slope factors, quantum yields, and excited state decay kinetics. These
      measurements revealed enhancement factors of the upconversion quantum yield of
      >10 000 in the low power region and an excitation power density-independent
      quantum yield of the downshifted emission at 1520 nm between 0.1 and 14%. The
      optimized shell thickness for combined vis and SWIR imaging was identified as 5
      nm. Moreover, lifetimes and quantum yields can be continuously tuned by shell
      thickness which can be exploited for lifetime multiplexing and encoding. The fact
      that we did not observe a saturation of the upconversion quantum yield or the
      excited state decay kinetics with increasing shell thickness is ascribed to a
      strong intermixing of the active core with the inert shell during the shelling
      procedure. This indicates the potential of spectroscopic tools to detect cation
      intermixing.

PMID- 29570284
TI  - Substrate Directed Asymmetric Reactions.
AB  - Historically, reagent controlled reactions (mechanism controlled reactions) have
      played a significant role in the asymmetric synthesis of complex structures. In
      contrast, today's asymmetric synthesis is greatly dependent on substrate directed
      approaches. In this approach, a polar functional group, namely, a "directing
      group", in the vicinity of the reactive site inside the substrate has been
      documented to preassociate with the chiral catalyst, which exerts stereodirecting
      influence by directing the reacting partner toward one of the enantiotopic faces
      of the reaction center. Those reactions usually proceed through exceptionally
      ordered transition states and result in extraordinary levels of stereoselection.
      Within the last four decades, the substrate directed approach has become an
      indispensible tool for the preparation of complex chiral frameworks starting
      directly from relatively simple achiral substrate molecules via asymmetric
      induction or various resolution techniques or both. Likewise, the substrate
      directed approach has been applied to functionalize enantiopure substrates
      bearing pre-exisiting stereocenters into complex structures as a single
      diastereomer. A classical example is Sharpless asymmetric epoxidation of allylic
      alcohols in which the free hydroxy function acts as an active anchor to a dimeric
      Ti-catalyst that controls the stereochemical outcome of the epoxidation process
      by transferring the oxidant enantioselectively. The principal aim of the present
      review is to give a general overview of substrate directed asymmetric
      transformations, a topic that has not yet been documented in the form of a
      concise review of recently developed approaches. Due to the large number of
      related applications, only recent advances that have been documented within the
      last two decades have been reviewed. Furthermore, in the current review, we have
      mainly highlighted asymmetric reactions that are controlled by abundant and
      frequently used directing groups such as hydroxy, amide, and sulfonamide groups.
      In addition, selected examples of a few important substrate-directed chemo-,
      regio-, and diastereoselective reactions have also been included in this review.

PMID- 29570285
TI  - Synthesis of Pyrimidine Fused Quinolines by Ligand-Free Copper-Catalyzed Domino
      Reactions.
AB  - Herein, we report two novel methods for the synthesis of pyrimidine fused
      quinolines using a one-pot C-C and C-N bond forming strategy from the reaction of
      6-aminouracils with 2-bromobenzaldehydes or 2-bromobenzyl bromide derivatives in
      the presence of 10 mol % CuCl2 without using any ligand. The reaction of 2
      bromobenzaldehyde or its derivatives with 6-aminouracils in the presence of K2CO3
      as base and a catalytic amount of CuCl2 in DMF medium under microwave heating
      conditions provides corresponding pyrimidine fused quinoline derivatives in good
      yields within 30 min. Alternatively, pyrimidine fused quinoline derivatives have
      been synthesized from the reaction of 2-bromobenzyl bromides with 6-aminouracil
      derivatives in the presence of molecular oxygen, CuCl2 (10 mol %), and K2CO3 as
      base in DMF under reflux conditions. Structures of all the products were
      unambiguously confirmed by spectroscopic techniques and by recording single
      crystal XRD of 3a.

PMID- 29570287
TI  - Uncertain Environmental Footprint of Current and Future Battery Electric
      Vehicles.
AB  - The future environmental impacts of battery electric vehicles (EVs) are very
      important given their expected dominance in future transport systems. Previous
      studies have shown these impacts to be highly uncertain, though a detailed
      treatment of this uncertainty is still lacking. We help to fill this gap by using
      Monte Carlo and global sensitivity analysis to quantify parametric uncertainty
      and also consider two additional factors that have not yet been addressed in the
      field. First, we include changes to driving patterns due to the introduction of
      autonomous and connected vehicles. Second, we deeply integrate scenario results
      from the IMAGE integrated assessment model into our life cycle database to
      include the impacts of changes to the electricity sector on the environmental
      burdens of producing and recharging future EVs. Future EVs are expected to have
      45-78% lower climate change impacts than current EVs. Electricity used for
      charging is the largest source of variability in results, though vehicle size,
      lifetime, driving patterns, and battery size also strongly contribute to
      variability. We also show that it is imperative to consider changes to the
      electricity sector when calculating upstream impacts of EVs, as without this,
      results could be overestimated by up to 75%.

PMID- 29570286
TI  - Hydration Structure and Dynamics of Inhibitor-Bound HIV-1 Protease.
AB  - Water is essential in many biological processes, and the hydration structure
      plays a critical role in facilitating protein folding, dynamics, and ligand
      binding. A variety of biophysical spectroscopic techniques have been used to
      probe the water solvating proteins, often complemented with molecular dynamics
      (MD) simulations to resolve the spatial and dynamic features of the hydration
      shell, but comparing relative water structure is challenging. In this study 1 MUs
      MD simulations were performed to identify and characterize hydration sites around
      HIV-1 protease bound to an inhibitor, darunavir (DRV). The water density,
      hydration site occupancy, extent and anisotropy of fluctuations, coordinated
      water molecules, and hydrogen bonds were characterized and compared to the
      properties of bulk water. The water density of the principal hydration shell was
      found to be higher than bulk, dependent on the topology and physiochemical
      identity of the biomolecular surface. The dynamics of water molecules occupying
      principal hydration sites was highly dependent on the number of water-water
      interactions and inversely correlated with hydrogen bonds to the protein
      inhibitor complex. While many waters were conserved following the symmetry of
      homodimeric HIV protease, the asymmetry induced by DRV resulted in asymmetric
      lower-occupancy hydration sites at the concave surface of the active site. Key
      interactions between water molecules and the protease, that stabilize the protein
      in the inhibited form, were altered in a drug resistant variant of the protease
      indicating that modulation of solvent-solute interactions might play a key role
      in conveying drug resistance. Our analysis provides insights into the interplay
      between an enzyme inhibitor complex and the hydration shell and has implications
      in elucidating water structure in a variety of biological processes and
      applications including ligand binding, inhibitor design, and resistance.

PMID- 29570288
TI  - A Molecular Dynamics-Quantum Mechanics Theoretical Study of DNA-Mediated Charge
      Transport in Hydrated Ionic Liquids.
AB  - Charge transport (CT) through biomolecules is of high significance in the
      research fields of biology, nanotechnology, and molecular devices. Inspired by
      our previous work that showed the binding of ionic liquid (IL) facilitated charge
      transport in duplex DNA, in silico simulation is a useful means to understand the
      microscopic mechanism of the facilitation phenomenon. Here molecular dynamics
      simulations (MD) of duplex DNA in water and hydrated ionic liquids were employed
      to explore the helical parameters. Principal component analysis was further
      applied to capture the subtle conformational changes of helical DNA upon
      different environmental impacts. Sequentially, CT rates were calculated by a
      QM/MM simulation of the flickering resonance model based upon MD trajectories.
      Herein, MD simulation illustrated that the binding of ionic liquids can restrain
      dynamic conformation and lower the on-site energy of the DNA base. Confined
      movement among the adjacent base pairs was highly related to the increase of
      electronic coupling among base pairs, which may lead DNA to a CT facilitated
      state. Sequentially combining MD and QM/MM analysis, the rational correlations
      among the binding modes, the conformational changes, and CT rates illustrated the
      facilitation effects from hydrated IL on DNA CT and supported a conformational
      gating mechanism.

PMID- 29570289
TI  - Systematic Evaluation of 2-Arylazocarboxylates and 2-Arylazocarboxamides as
      Mitsunobu Reagents.
AB  - 2-Arylazocarboxylate and 2-arylazocarboxamide derivatives can serve as
      replacements of typical Mitsunobu reagents such as diethyl azodicarboxylate. A
      systematic investigation of the reactivity and physical properties of those azo
      compounds has revealed that they have an excellent ability as Mitsunobu reagents.
      These reagents show similar or superior reactivity as compared to the known azo
      reagents and are applicable to the broad scope of substrates. p Ka and steric
      effects of substrates have been investigated, and the limitation of the Mitsunobu
      reaction can be overcome by choosing suitable reagents from the library of 2
      arylazocarboxylate and 2-aryl azocarboxamide derivatives. Convenient recovery of
      azo reagents is available by one-pot iron-catalyzed aerobic oxidation, for
      example. SC-DSC analysis of representative 2-arylazocarboxylate and 2
      arylazocarboxamide derivatives has shown high thermal stability, indicating that
      these azo reagents possess lower chemical hazard compared with typical azo
      reagents.

PMID- 29570290
TI  - Mechanochemistry-Based Synthesis of Highly Crystalline gamma-Zirconium Phosphate
      for Selective Ion Exchange.
AB  - Highly crystalline gamma-zirconium phosphate has been synthesized by a novel
      minimalistic approach and investigated as a selective ion exchanger for cesium,
      ammonium and potassium. In contrast to current solution-based preparations, the
      mechanochemistry-based synthesis provides easy access to gamma-zirconium
      phosphate with short synthesis times and low crystallization temperature. The
      addition of NaF as a mineralizer increases the crystallinity of gamma-zirconium
      phosphate, which forms micrometer-sized uniformly shaped rectangular platelets.
      The crystalline material has extremely high selectivity to cesium even in the
      presence of 1000- or 500-fold excess Na+ or Ca2+, respectively. The removal
      efficiency was >98% in the pH range of 2-5.5. As an ion exchanger for
      purification of dialysate, crystalline gamma-zirconium phosphate shows higher
      uptake of ammonium and potassium ions than the amorphous gel compound currently
      used in sorbent cartridges. This sustainable protocol opens up opportunities for
      many practical applications of gamma-zirconium phosphate.

PMID- 29570291
TI  - The Intricate Case of Tetramethyleneethane: A Full Configuration Interaction
      Quantum Monte Carlo Benchmark and Multireference Coupled Cluster Studies.
AB  - We have performed a full configuration interaction (FCI) quality benchmark
      calculation for the tetramethyleneethane molecule in the cc-pVTZ basis set
      employing a subset of complete active space second order perturbation theory,
      CASPT2(6,6), natural orbitals for the FCI quantum Monte Carlo calculation. The
      results are in an excellent agreement with the previous large scale diffusion
      Monte Carlo calculations by Pozun et al. and available experimental results. Our
      computations verified that there is a maximum on the potential energy surface
      (PES) of the ground singlet state (1A) 45 degrees  torsional angle, and the
      corresponding vertical singlet-triplet energy gap is 0.01 eV. We have employed
      this benchmark for the assessment of the accuracy of Mukherjee's coupled clusters
      with up to triple excitations (MkCCSDT) and CCSD tailored by the density matrix
      renormalization group method (DMRG). Multireference MkCCSDT with CAS(2,2) model
      space, though giving good values for the singlet-triplet energy gap, is not able
      to properly describe the shape of the multireference singlet PES. Similarly,
      DMRG(24,25) is not able to correctly capture the shape of the singlet surface,
      due to the missing dynamic correlation. On the other hand, the DMRG-tailored CCSD
      method describes the shape of the ground singlet state with excellent accuracy
      but for the correct ordering requires computation of the zero-spin-projection
      component of the triplet state (3B1).

PMID- 29570292
TI  - 2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4
      (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety.
AB  - Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a
      number of biological processes and/or diseases, including diabetes, cancer,
      inflammation, and angiogenesis. With a majority of the members of our lead series
      (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought
      design avenues that would eliminate this risk. One such approach arose from the
      observation that carboxylic acid-based intermediates employed in our discovery
      efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk.
      The medicinal chemistry effort that led to the discovery of this central nervous
      system-impaired inhibitor together with its preclinical safety profile is
      described.

PMID- 29570293
TI  - Is pi-Stacking Prone To Accelerate Singlet-Singlet Energy Transfers?
AB  - pi-Stacking is the most common structural feature that dictates the optical and
      electronic properties of chromophores in the solid state. Herein, a
      unidirectional singlet-singlet energy-transfer dyad has been designed to test the
      effect of pi-stacking of zinc(II) porphyrin, [Zn2], as a slipped dimer acceptor
      using a BODIPY unit, [bod], as the donor, bridged by the linker C6H4C=CC6H4. The
      rate of singlet energy transfer, kET(S1), at 298 K ( kET(S1) = 4.5 * 1010 s-1)
      extracted through the change in fluorescence lifetime, tauF, of [bod] in the
      presence (27.1 ps) and the absence of [Zn2] (4.61 ns) from Streak camera
      measurements, and the rise time of the acceptor signal in femtosecond transient
      absorption spectra (22.0 ps), is faster than most literature cases where no pi
      stacking effect exists (i.e., monoporphyrin units). At 77 K, the tauF of [bod]
      increases to 45.3 ps, indicating that kET(S1) decreases by 2-fold (2.2 * 1010 s
      1), a value similar to most values reported in the literature, thus suggesting
      that the higher value at 298 K is thermally promoted at a higher temperature.

PMID- 29570294
TI  - Analyzing Fluxional Molecules Using DORI.
AB  - The Density Overlap Region Indicator (DORI) is a density-based scalar field that
      reveals covalent bonding patterns and noncovalent interactions in the same value
      range. This work goes beyond the traditional static quantum chemistry use of
      scalar fields and illustrates the suitability of DORI for analyzing geometrical
      and electronic signatures in highly fluxional molecular systems. Examples include
      a dithiocyclophane, which possesses multiple local minima with differing extents
      of pi-stacking interactions and a temperature dependent rotation of a molecular
      rotor, where the descriptor is employed to capture fingerprints of CH-pi and pi
      pi interactions. Finally, DORI serves to examine the fluctuating pi-conjugation
      pathway of a photochromic torsional switch (PTS). Attention is also placed on
      postprocessing the large amount of generated data and juxtaposing DORI with a
      data-driven low-dimensional representation of the structural landscape.

PMID- 29570295
TI  - Comment on "Insights into the Nature of the Chemical Bonding in Thiophene-2-thiol
      from X-ray Absorption Spectroscopy".

PMID- 29570296
TI  - Micelle Formation in Alkyl Sulfate Surfactants Using Dissipative Particle
      Dynamics.
AB  - We use dissipative particle dynamics (DPD) to study micelle formation in alkyl
      sulfate surfactants, with alkyl chain lengths ranging from 6 to 12 carbon atoms.
      We extend our recent DPD force field [ J. Chem. Phys. 2017 , 147 , 094503 ] to
      include a charged sulfate chemical group and aqueous sodium ions. With this
      model, we achieve good agreement with the experimentally reported critical
      micelle concentrations (CMCs) and can match the trend in mean aggregation numbers
      versus alkyl chain length. We determine the CMC by fitting a charged pseudophase
      model to the dependence of the free surfactant on the total surfactant
      concentration above the CMC and compare it with a direct operational definition
      of the CMC as the point at which half of the surfactant is classed as micellar
      and half as monomers and submicellar aggregates. We find that the latter provides
      the best agreement with experimental results. Finally, with the same model, we
      are able to observe the sphere-to-rod morphological transition for sodium dodecyl
      sulfate (SDS) micelles and determine that it corresponds to SDS concentrations in
      the region of 300-500 mM.

PMID- 29570297
TI  - Eliminating Spurious Zero-Efficiency FRET States in Diffusion-Based Single
      Molecule Confocal Microscopy.
AB  - Single-molecule Forster resonance energy transfer (smFRET) of freely diffusing
      biomolecules using confocal microscopy is a simple and powerful technique for
      measuring conformation and dynamics. However, a spurious zero-FRET population can
      significantly distort the measured histograms and lead to incorrect results,
      particularly in measurements of intrinsically low-FRET systems. Using a model
      system consisting of duplex DNAs, we show that there are two important
      contributions to the zero-FRET state: (1) formation of a dark triplet state of
      the acceptor dye and (2) the presence of donor-only strands due to incomplete
      hybridization between donor- and acceptor-labeled strands. The combined strategy
      of using Trolox as a triplet-state quencher and labeling the same DNA strand with
      donor and acceptor dyes effectively eliminates the zero-FRET population, even for
      constructs with intrinsically low FRET efficiencies. This strategy allows us to
      perform smFRET experiments using a simple confocal microscope with improved
      accuracy.

PMID- 29570298
TI  - Iron Oxide Nanoparticles-Based Vaccine Delivery for Cancer Treatment.
AB  - Modern therapeutic cancer vaccines need simple and effective formulations to
      enhance both humoral and cellular immune responses. Nanoparticles have obtained
      more and more attention in the development of vaccine delivery platforms.
      Moreover, nanoparticles-based vaccine delivery platform has high potential for
      improving the immunogenicity of vaccine. The Food and Drug Administration (FDA)
      has approved many types of iron oxide nanoparticles for clinical use, such as
      treating iron deficiency, contrast agents for magnetic resonance imaging (MRI)
      and drug delivery platforms. In this study, we explored a novel combined use of
      iron oxide nanoparticles (superparamagnetic Fe3O4 nanoparticles) as a vaccine
      delivery platform and immune potentiator, and investigated how this formulation
      affected cytokine expression in macrophages and dendritic cells (DCs) in vitro
      and tumor growth in vivo. Comparing with soluble OVA alone and iron oxide
      nanoparticles alone, we found significant differences in immune responses and
      tumor inhibition induced by OVA formulated with iron oxide nanoparticles. Our
      iron oxide nanoparticles greatly promoted the activation of immune cells and
      cytokine production, inducing potent humoral and cellular immune responses. These
      results suggest that this nanoparticle-based delivery system has strong potential
      to be utilized as a general platform for cancer vaccines.

PMID- 29570299
TI  - GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to
      Clinical Liposomal Formulation for Ovarian Cancer Treatment.
AB  - Ovarian cancer as a recurrent disease is often refractory to treatment including
      pegylated liposomal doxorubicin hydrochloride (Lipo-Dox). Here, GE11 peptide
      modified reversibly cross-linked polymersomal doxorubicin (GE11-PS-Dox) was
      investigated as an advanced treatment for SKOV3 human ovarian tumors, which
      overexpress epidermal growth factor receptor (EGFR). The in vitro experiments
      using SKOV3 cancer cells demonstrated that GE11-PS-Dox induced obviously higher
      cellular uptake, Dox delivery to the nuclei, and antitumor activity than the
      nontargeted PS-Dox and Lipo-Dox controls. In vivo biodistribution experiments
      displayed 2.5-fold higher tumor accumulation for GE11-PS-Dox as compared to Lipo
      Dox. Notably, GE11-PS-Dox could effectively suppress the progression of SKOV3
      tumors and cause little adverse effects at 12 mg of Dox equiv/kg, leading to a
      remarkably increased survival rate of 100% over 78 days. In contrast, continued
      tumor growth and body weight loss were discerned for Lipo-Dox treated mice at 6
      mg of Dox equiv/kg. Moreover, a single dose of GE11-PS-Dox at 60 mg of Dox
      equiv/kg showed also effective treatment and low toxicity toward SKOV3-tumor
      bearing mice. GE11-directed reversibly cross-linked polymersomal doxorubicin has
      emerged as an advanced alternative to Lipo-Dox for treatment of EGFR
      overexpressing ovarian cancers.

PMID- 29570300
TI  - Access to Quaternary Stereogenic Centers via Rhodium(III)-Catalyzed Annulations
      between 2-Phenylindoles and Ketenes.
AB  - Rh(III)-catalyzed C-H activation of arenes and mild oxidative [4 + 2] annulative
      coupling with ketenes have been realized. The uniquely high reactivity of the
      C(3) of 2-phenylindoles was successfully utilized to facilitate the reductive
      elimination process, leading to efficient synthesis of cyclic products with a
      quaternary carbon stereocenter.

PMID- 29570301
TI  - Polarization Effects in Binary [BMIM+][BF4-]/1,2-Dichloroethane, Acetone,
      Acetonitrile, and Water Electrolytes.
AB  - Organic electrolytes are unique in that their constituent solvents may be of much
      lower dielectric strength than water. This is because the ions of organic
      electrolytes are often those that comprise room-temperature ionic liquids, which
      are surprisingly miscible with many different organic solvents of low dielectric
      strength. Strong ion correlation results from the relatively low dielectric
      screening of the solvent, resulting in properties that can substantially deviate
      from Debye-Huckel descriptions; in addition remains the fundamental question of
      why the ionic liquids and low dielectric solvents are even miscible in the first
      place. In this work, we study electrolyte mixtures composed of the room
      temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate
      [BMIM+][BF4-] mixed with four solvents of systematically varying dielectric
      strength, 1,2-dichloroethane, acetone, acetonitrile, and water. We show that
      miscibility with the lowest dielectric solvent, dichloroethane, is directly
      attributed to ion solvation enhancement mediated by both electronic and
      conformational polarization of the solvent molecules. A strong dielectric
      enhancement results from the ~70-80% increase in solvent dipole moments at high
      ion content, providing significantly better solvation than predicted by the bulk
      solvent dielectric strength. This implies a general mechanism for miscibility of
      ionic liquids with low dielectric solvents, through which ions effectly create
      their own solvation dipoles by polarizing the local environment. From a purely
      computational perspective, our results imply that explicitly polarizable force
      fields are essential for modeling many of the organic electrolytes that are used
      in electrochemical applications.

PMID- 29570303
TI  - Polarization Control with Plasmonic Antenna Tips: A Universal Approach to Optical
      Nanocrystallography and Vector-Field Imaging.
AB  - Controlling the propagation and polarization vectors in linear and nonlinear
      optical spectroscopy enables us to probe the anisotropy of optical responses
      providing structural symmetry selective contrast in optical imaging. Here, we
      present a novel tilted antenna-tip approach to control the optical vector-field
      by breaking the axial symmetry of the nanoprobe in tip-enhanced near-field
      microscopy. This gives rise to a localized plasmonic antenna effect with
      significantly enhanced optical field vectors with control of both in-plane and
      out-of-plane components. We use the resulting vector-field specificity in the
      symmetry selective nonlinear optical response of second-harmonic generation (SHG)
      for a generalized approach to optical nanocrystallography and imaging. In tip
      enhanced SHG imaging of monolayer MoS2 films and single-crystalline ferroelectric
      YMnO3, we reveal nanocrystallographic details of domain boundaries and domain
      topology with enhanced sensitivity and nanoscale spatial resolution. The approach
      is applicable to any anisotropic linear and nonlinear optical response and
      enables the optical nanocrystallographic imaging of molecular or quantum
      materials.

PMID- 29570302
TI  - DNA-Mediated Size-Selective Nanoparticle Assembly for Multiplexed Surface
      Encoding.
AB  - Multiplexed surface encoding is achieved by positioning two different sizes of
      gold nanocubes on gold surfaces with precisely defined locations for each
      particle via template-confined, DNA-mediated nanoparticle assembly. As a proof-of
      concept demonstration, cubes with 86 and 63 nm edge lengths are assembled into
      arrangements that physically and spectrally encrypt two sets of patterns in the
      same location. These patterns can be decrypted by mapping the absorption
      intensity of the substrate at lambda = 773 and 687 nm, respectively. This
      multiplexed encoding platform dramatically increases the sophistication and
      density of codes that can be written using colloidal nanoparticles, which may
      enable high-security, high-resolution encoding applications.

PMID- 29570304
TI  - Nanowires Bending over Backward from Strain Partitioning in Asymmetric Core-Shell
      Heterostructures.
AB  - The flexibility and quasi-one-dimensional nature of nanowires offer wide-ranging
      possibilities for novel heterostructure design and strain engineering. In this
      work, we realize arrays of extremely and controllably bent nanowires comprising
      lattice-mismatched and highly asymmetric core-shell heterostructures. Strain
      sharing across the nanowire heterostructures is sufficient to bend vertical
      nanowires over backward to contact either neighboring nanowires or the substrate
      itself, presenting new possibilities for designing nanowire networks and
      interconnects. Photoluminescence spectroscopy on bent-nanowire heterostructures
      reveals that spatially varying strain fields induce charge carrier drift toward
      the tensile-strained outside of the nanowires, and that the polarization response
      of absorbed and emitted light is controlled by the bending direction. This
      unconventional strain field is employed for light emission by placing an active
      region of quantum dots at the outer side of a bent nanowire to exploit the
      carrier drift and tensile strain. These results demonstrate how bending in
      nanoheterostructures opens up new degrees of freedom for strain and device
      engineering.

PMID- 29570305
TI  - Interaction Enthalpy of Side Chain and Backbone Amides in Polyglutamine Solution
      Monomers and Fibrils.
AB  - We determined an empirical correlation that relates the amide I vibrational band
      frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding,
      van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We
      used this correlation to determine the Q side chain carbonyl interaction enthalpy
      (Delta Hint) in monomeric and amyloid-like fibril conformations of D2Q10K2 (Q10).
      We independently verified these Delta Hint values through molecular dynamics
      simulations that showed excellent agreement with experiments. We found that side
      chain-side chain and side chain-peptide backbone interactions in fibrils and
      monomers are more enthalpically favorable than are Q side chain-water
      interactions. Q10 fibrils also showed a more favorable Delta Hint for side chain
      side chain interactions compared to backbone-backbone interactions. This work
      experimentally demonstrates that interamide side chain interactions are important
      in the formation and stabilization of polyQ fibrils.

PMID- 29570306
TI  - Dual-Gated Active Metasurface at 1550 nm with Wide (>300 degrees ) Phase
      Tunability.
AB  - Active metasurfaces composed of electrically reconfigurable nanoscale
      subwavelength antenna arrays can enable real-time control of scattered light
      amplitude and phase. Achievement of widely tunable phase and amplitude in chip
      based active metasurfaces operating at or near 1550 nm wavelength has
      considerable potential for active beam steering, dynamic hologram rendition, and
      realization of flat optics with reconfigurable focal lengths. Previously,
      electrically tunable conducting oxide-based reflectarray metasurfaces have
      demonstrated dynamic phase control of reflected light with a maximum phase shift
      of 184 degrees  ( Nano Lett. 2016 , 16 , 5319 ). Here, we introduce a dual-gated
      reflectarray metasurface architecture that enables much wider (>300 degrees )
      phase tunability. We explore light-matter interactions with dual-gated
      metasurface elements that incorporate two independent voltage-controlled MOS
      field effect channels connected in series to form a single metasurface element
      that enables wider phase tunability. Using indium tin oxide (ITO) as the active
      metasurface material and a composite hafnia/alumina gate dielectric, we
      demonstrate a prototype dual-gated metasurface with a continuous phase shift from
      0 to 303 degrees  and a relative reflectance modulation of 89% under applied
      voltage bias of 6.5 V.

PMID- 29570307
TI  - Na2V6O16.3H2O Barnesite Nanorod: An Open Door to Display a Stable and High Energy
      for Aqueous Rechargeable Zn-Ion Batteries as Cathodes.
AB  - Owing to their safety and low cost, aqueous rechargeable Zn-ion batteries
      (ARZIBs) are currently more feasible for grid-scale applications, as compared to
      their alkali counterparts such as lithium- and sodium-ion batteries (LIBs and
      SIBs), for both aqueous and nonaqueous systems. However, the materials used in
      ARZIBs have a poor rate capability and inadequate cycle lifespan, serving as a
      major handicap for long-term storage applications. Here, we report vanadium-based
      Na2V6O16.3H2O nanorods employed as a positive electrode for ARZIBs, which display
      superior electrochemical Zn storage properties. A reversible Zn2+-ion
      (de)intercalation reaction describing the storage mechanism is revealed using the
      in situ synchrotron X-ray diffraction technique. This cathode material delivers a
      very high rate capability and high capacity retention of more than 80% over 1000
      cycles, at a current rate of 40C (1C = 361 mA g-1). The battery offers a specific
      energy of 90 W h kg-1 at a specific power of 15.8 KW kg-1, enlightening the
      material advantages for an eco-friendly atmosphere.

PMID- 29570308
TI  - Passivation of Plasmonic Colors on Bulk Silver by Atomic Layer Deposition of
      Aluminum Oxide.
AB  - We report the passivation of angle-independent plasmonic colors on bulk silver by
      atomic layer deposition (ALD) of thin films of aluminum oxide. The colors are
      rendered by silver nanoparticles produced by laser ablation and redeposition on
      silver. We then apply a two-step approach to aluminum oxide conformal film
      formation via ALD. In the first step, a low-density film is deposited at low
      temperature to preserve and pin the silver nanoparticles. In the second step, a
      second denser film is deposited at a higher temperature to provide tarnish
      protection. This approach successfully protects the silver and plasmonic colors
      against tarnishing, humidity, and temperature, as demonstrated by aggressive
      exposure trials. The processing time associated with deposition of the conformal
      passivation layers meets industry requirements, and the approach is compatible
      with mass manufacturing.

PMID- 29570309
TI  - Nanoscale Mapping and Control of Antenna-Coupling Strength for Bright Single
      Photon Sources.
AB  - Cavity quantum electrodynamics is the art of enhancing light-matter interaction
      of photon emitters in cavities with opportunities for sensing, quantum
      information, and energy capture technologies. To boost emitter-cavity
      interaction, that is, coupling strength g, ultrahigh quality cavities have been
      concocted yielding photon trapping times of microsecondsy to milliseconds.
      However, such high- Q cavities give poor photon output, hindering applications.
      To preserve high photon output, it is advantageous to strive for highly localized
      electric fields in radiatively lossy cavities. Nanophotonic antennas are ideal
      candidates combining low- Q factors with deeply localized mode volumes, allowing
      large g, provided the emitter is positioned exactly right inside the nanoscale
      mode volume. Here, with nanometer resolution, we map and tune the coupling
      strength between a dipole nanoantenna-cavity and a single molecule, obtaining a
      coupling rate of gmax ~ 200 GHz. Together with accelerated single photon output,
      this provides ideal conditions for fast and pure nonclassical single photon
      emission with brightness exceeding 109 photons/sec. Clearly, nanoantennas acting
      as "bad" cavities offer an optimal regime for strong coupling g to deliver bright
      on-demand and ultrafast single photon nanosources for quantum technologies.

PMID- 29570310
TI  - Fully Kinetic Simulation of 3D Kinetic Alfven Turbulence.
AB  - We present results from a three-dimensional particle-in-cell simulation of plasma
      turbulence, resembling the plasma conditions found at kinetic scales of the solar
      wind. The spectral properties of the turbulence in the subion range are
      consistent with theoretical expectations for kinetic Alfven waves. Furthermore,
      we calculate the local anisotropy, defined by the relation k_{?}(k_{?}), where
      k_{?} is a characteristic wave number along the local mean magnetic field at
      perpendicular scale l_{?}~1/k_{?}. The subion range anisotropy is scale dependent
      with k_{?}<k_{?} and the ratio of linear to nonlinear time scales is of order
      unity, suggesting that the kinetic cascade is close to a state of critical
      balance. Our results compare favorably against a number of in situ solar wind
      observations and demonstrate-from first principles-the feasibility of plasma
      turbulence models based on a critically balanced cascade of kinetic Alfven waves.

PMID- 29570311
TI  - Landauer-Buttiker Approach to Strongly Coupled Quantum Thermodynamics: Inside
      Outside Duality of Entropy Evolution.
AB  - We develop a Landauer-Buttiker theory of entropy evolution in time-dependent,
      strongly coupled electron systems. The formalism naturally avoids the problem of
      the system-bath distinction by defining the entropy current in the attached
      leads. This current can then be used to infer changes of the entropy of the
      system which we refer to as the inside-outside duality. We carry out this program
      in an adiabatic expansion up to first order beyond the quasistatic limit. When
      combined with particle and energy currents, as well as the work required to
      change an external potential, our formalism provides a full thermodynamic
      description, applicable to arbitrary noninteracting electron systems in contact
      with reservoirs. This provides a clear understanding of the relation between heat
      and entropy currents generated by time-dependent potentials and their connection
      to the occurring dissipation.

PMID- 29570312
TI  - Evolution of Nanowire Transmon Qubits and Their Coherence in a Magnetic Field.
AB  - We present an experimental study of flux- and gate-tunable nanowire transmons
      with state-of-the-art relaxation time allowing quantitative extraction of flux
      and charge noise coupling to the Josephson energy. We evidence coherence sweet
      spots for charge, tuned by voltage on a proximal side gate, where first order
      sensitivity to switching two-level systems and background 1/f noise is minimized.
      Next, we investigate the evolution of a nanowire transmon in a parallel magnetic
      field up to 70 mT, the upper bound set by the closing of the induced gap. Several
      features observed in the field dependence of qubit energy relaxation and
      dephasing times are not fully understood. Using nanowires with a thinner,
      partially covering Al shell will enable operation of these circuits up to 0.5 T,
      a regime relevant for topological quantum computation and other applications.

PMID- 29570313
TI  - Quantum Monte Carlo Simulation of Frustrated Kondo Lattice Models.
AB  - The absence of the negative sign problem in quantum Monte Carlo simulations of
      spin and fermion systems has different origins. World-line based algorithms for
      spins require positivity of matrix elements whereas auxiliary field approaches
      for fermions depend on symmetries such as particle-hole symmetry. For negative
      sign-free spin and fermionic systems, we show that one can formulate a negative
      sign-free auxiliary field quantum Monte Carlo algorithm that allows Kondo
      coupling of fermions with the spins. Using this general approach, we study a half
      filled Kondo lattice model on the honeycomb lattice with geometric frustration.
      In addition to the conventional Kondo insulator and antiferromagnetically ordered
      phases, we find a partial Kondo screened state where spins are selectively
      screened so as to alleviate frustration, and the lattice rotation symmetry is
      broken nematically.

PMID- 29570315
TI  - Suppression of Quasiparticle Scattering Signals in Bilayer Graphene Due to Layer
      Polarization and Destructive Interference.
AB  - We study chemically gated bilayer graphene using scanning tunneling microscopy
      and spectroscopy complemented by tight-binding calculations. Gating is achieved
      by intercalating Cs between bilayer graphene and Ir(111), thereby shifting the
      conduction band minima below the chemical potential. Scattering between
      electronic states (both intraband and interband) is detected via quasiparticle
      interference. However, not all expected processes are visible in our experiment.
      We uncover two general effects causing this suppression: first, intercalation
      leads to an asymmetrical distribution of the states within the two layers, which
      significantly reduces the scanning tunneling spectroscopy signal of standing
      waves mainly present in the lower layer; second, forward scattering processes,
      connecting points on the constant energy contours with parallel velocities, do
      not produce pronounced standing waves due to destructive interference. We present
      a theory to describe the interference signal for a general n-band material.

PMID- 29570316
TI  - Emission Noise in an Interacting Quantum Dot: Role of Inelastic Scattering and
      Asymmetric Coupling to the Reservoirs.
AB  - A theory is developed for the emission noise at frequency nu in a quantum dot in
      the presence of Coulomb interactions and asymmetric couplings to the reservoirs.
      We give an analytical expression for the noise in terms of the various
      transmission amplitudes. Including the inelastic scattering contribution, it can
      be seen as the analog of the Meir-Wingreen formula for the current. A physical
      interpretation is given on the basis of the transmission of one electron-hole
      pair to the concerned reservoir where it emits an energy after recombination. We
      then treat the interactions by solving the self-consistent equations of motion
      for the Green functions. The results for the noise derivative versus eV show a
      zero value until eV=hnu, followed by a Kondo peak in the Kondo regime, in good
      agreement with recent measurements in carbon nanotube quantum dots.

PMID- 29570317
TI  - Nonadiabatic Breaking of Topological Pumping.
AB  - We study Thouless pumping out of the adiabatic limit. Our findings show that
      despite its topological nature, this phenomenon is not generically robust to
      nonadiabatic effects. Indeed, we find that the Floquet diagonal ensemble value of
      the pumped charge shows a deviation from the topologically quantized limit which
      is quadratic in the driving frequency for a sudden switch on of the driving. This
      is reflected also in the charge pumped in a single period, which shows a
      nonanalytic behavior on top of an overall quadratic decrease. Exponentially small
      corrections are recovered only with a careful tailoring of the driving protocol.
      We also discuss thermal effects and the experimental feasibility of observing
      such a deviation.

PMID- 29570318
TI  - Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation.
AB  - A key question concerning the three-body fragmentation of polyatomic molecules is
      the distinction of sequential and concerted mechanisms, i.e., the stepwise or
      simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into
      O^{+}+C^{+}+S^{+} and employing coincidence momentum imaging, we demonstrate a
      novel method that enables the clear separation of sequential and concerted
      breakup. The separation is accomplished by analyzing the three-body fragmentation
      in the native frame associated with each step and taking advantage of the
      rotation of the intermediate molecular fragment, CO^{2+} or CS^{2+}, before its
      unimolecular dissociation. This native-frame method works for any projectile
      (electrons, ions, or photons), provides details on each step of the sequential
      breakup, and enables the retrieval of the relevant spectra for sequential and
      concerted breakup separately. Specifically, this allows the determination of the
      branching ratio of all these processes in OCS^{3+} breakup. Moreover, we find
      that the first step of sequential breakup is tightly aligned along the laser
      polarization and identify the likely electronic states of the intermediate
      dication that undergo unimolecular dissociation in the second step. Finally, the
      separated concerted breakup spectra show clearly that the central carbon atom is
      preferentially ejected perpendicular to the laser field.

PMID- 29570319
TI  - Role of Sink Density in Nonequilibrium Chemical Redistribution in Alloys.
AB  - Nonequilibrium chemical redistribution in open systems submitted to external
      forces, such as particle irradiation, leads to changes in the structural
      properties of the material, potentially driving the system to failure. Such
      redistribution is controlled by the complex interplay between the production of
      point defects, atomic transport rates, and the sink character of the
      microstructure. In this work, we analyze this interplay by means of a kinetic
      Monte Carlo (KMC) framework with an underlying atomistic model for the Fe-Cr
      model alloy to study the effect of ideal defect sinks on Cr concentration
      profiles, with a particular focus on the role of interface density. We observe
      that the amount of segregation decreases linearly with decreasing interface
      spacing. Within the framework of the thermodynamics of irreversible processes, a
      general analytical model is derived and assessed against the KMC simulations to
      elucidate the structure-property relationship of this system. Interestingly, in
      the kinetic regime where elimination of point defects at sinks is dominant over
      bulk recombination, the solute segregation does not directly depend on the dose
      rate but only on the density of sinks. This model provides new insight into the
      design of microstructures that mitigate chemical redistribution and improve
      radiation tolerance.

PMID- 29570320
TI  - Exact Results for the Nonergodicity of d-Dimensional Generalized Levy Walks.
AB  - We provide analytical results for the ensemble-averaged and time-averaged squared
      displacement, and the randomness of the latter, in the full two-dimensional
      parameter space of the d-dimensional generalized Levy walk introduced by
      Shlesinger et al. [Phys. Rev. Lett. 58, 1100 (1987)PRLTAO0031
      900710.1103/PhysRevLett.58.1100]. In certain regions of the parameter plane, we
      obtain surprising results such as the divergence of the mean-squared
      displacements, the divergence of the ergodicity breaking parameter despite a
      finite mean-squared displacement, and subdiffusion which appears superdiffusive
      when one only considers time averages.

PMID- 29570321
TI  - Role of City Texture in Urban Heat Islands at Nighttime.
AB  - An urban heat island (UHI) is a climate phenomenon that results in an increased
      air temperature in cities when compared to their rural surroundings. In this
      Letter, the dependence of an UHI on urban geometry is studied. Multiyear urban
      rural temperature differences and building footprints data combined with a heat
      radiation scaling model are used to demonstrate for more than 50 cities worldwide
      that city texture-measured by a building distribution function and the sky view
      factor-explains city-to-city variations in nocturnal UHIs. Our results show a
      strong correlation between nocturnal UHIs and the city texture.

PMID- 29570322
TI  - Tunable Gamma-K Valley Populations in Hole-Doped Trilayer WSe_{2}.
AB  - We present a combined experimental and theoretical study of valley populations in
      the valence bands of trilayer WSe_{2}. Shubnikov-de Haas oscillations show that
      trilayer holes populate two distinct subbands associated with the K and Gamma
      valleys, with effective masses 0.5m_{e} and 1.2m_{e}, respectively; m_{e} is the
      bare electron mass. At a fixed total hole density, an applied transverse electric
      field transfers holes from Gamma orbitals to K orbitals. We are able to explain
      this behavior in terms of the larger layer polarizability of the K orbital
      subband.

PMID- 29570323
TI  - Ultrafast Two-Dimensional Infrared Spectroscopy of a Quasifree Rotor: J
      Scrambling and Perfectly Anticorrelated Cross Peaks.
AB  - Ultrafast two-dimensional infrared (2DIR) spectra of the N_{2}O nu_{3} mode in
      moderately dense SF_{6} gas exhibit complex line shapes with diagonal and
      antidiagonal features in contrast to condensed phase vibrational 2DIR
      spectroscopy. Observed spectra for this quasifree rotor system are well captured
      by a model that includes all 36 possible rovibrational pathways and treats P
      (DeltaJ=-1) and R (DeltaJ=+1) branch resonances as distinct Kubo line shape
      features. Transition frequency correlation decay is due to J scrambling within
      one to two gas collisions at each density. Studies of supercritical solvation and
      relaxation at high pressure and temperature are enabled by this methodology.

PMID- 29570324
TI  - Black Hole Entropy from Bondi-Metzner-Sachs Symmetry at the Horizon.
AB  - Near the horizon, the obvious symmetries of a black hole spacetime-the horizon
      preserving diffeomorphisms-are enhanced to a larger symmetry group with a three
      dimensional Bondi-Metzner-Sachs algebra. Using dimensional reduction and
      covariant phase space techniques, I investigate this augmented symmetry and show
      that it is strong enough to determine the black hole entropy in any dimension.

PMID- 29570325
TI  - Strong Anisotropic Spin-Orbit Interaction Induced in Graphene by Monolayer
      WS_{2}.
AB  - We demonstrate strong anisotropic spin-orbit interaction (SOI) in graphene
      induced by monolayer WS_{2}. Direct comparison between graphene-monolayer WS_{2}
      and graphene-bulk WS_{2} systems in magnetotransport measurements reveals that
      monolayer transition metal dichalcogenide can induce much stronger SOI than bulk.
      Detailed theoretical analysis of the weak antilocalization curves gives an
      estimated spin-orbit energy (E_{so}) higher than 10 meV. The symmetry of the
      induced SOI is also discussed, and the dominant z->-z symmetric SOI can only
      explain the experimental results. Spin relaxation by the Elliot-Yafet mechanism
      and anomalous resistance increase with temperature close to the Dirac point
      indicates Kane-Mele SOI induced in graphene.

PMID- 29570326
TI  - Interplay of Phonon and Exciton-Mediated Superconductivity in Hybrid
      Semiconductor-Superconductor Structures.
AB  - We predict a strong enhancement of the critical temperature in a conventional
      Bardeen-Cooper-Schrieffer (BCS) superconductor in the presence of a bosonic
      condensate of exciton polaritons. The effect depends strongly on the ratio of the
      cutoff frequencies for phonon and exciton-polariton mediated BCS
      superconductivity, respectively. We also discuss a possible design of hybrid
      semiconductor-superconductor structures suitable for the experimental observation
      of such an effect.

PMID- 29570327
TI  - Charge Transfer Effects in Naturally Occurring van der Waals Heterostructures
      (PbSe)_{1.16}(TiSe_{2})_{m} (m=1, 2).
AB  - van der Waals heterostructures (VDWHs) exhibit rich properties and thus has
      potential for applications, and charge transfer between different layers in a
      heterostructure often dominates its properties and device performance. It is thus
      critical to reveal and understand the charge transfer effects in VDWHs, for which
      electronic structure measurements have proven to be effective. Using angle
      resolved photoemission spectroscopy, we studied the electronic structures of
      (PbSe)_{1.16}(TiSe_{2})_{m} (m=1, 2), which are naturally occurring VDWHs, and
      discovered several striking charge transfer effects. When the thickness of the
      TiSe_{2} layers is halved from m=2 to m=1, the amount of charge transferred
      increases unexpectedly by more than 250%. This is accompanied by a dramatic drop
      in the electron-phonon interaction strength far beyond the prediction by first
      principles calculations and, consequently, superconductivity only exists in the
      m=2 compound with strong electron-phonon interaction, albeit with lower carrier
      density. Furthermore, we found that the amount of charge transferred in both
      compounds is nearly halved when warmed from below 10 K to room temperature, due
      to the different thermal expansion coefficients of the constituent layers of
      these misfit compounds. These unprecedentedly large charge transfer effects might
      widely exist in VDWHs composed of metal-semiconductor contacts; thus, our results
      provide important insights for further understanding and applications of VDWHs.

PMID- 29570328
TI  - Catching a New Force by the Tail.
AB  - The Large Hadron Collider (LHC) is sensitive to new heavy gauge bosons that
      produce narrow peaks in the dilepton invariant mass spectrum up to about
      m_{Z^{'}}~5  TeV Z^{'}s that are too heavy to produce directly can reveal their
      presence through interference with standard model dilepton production. We show
      that the LHC can significantly extend the mass reach for such Z^{'}s by
      performing precision measurements of the shape of the dilepton invariant mass
      spectrum. The high-luminosity LHC can exclude, with 95% confidence, new gauge
      bosons as heavy as m_{Z^{'}}~10-20  TeV that couple with gauge coupling strength
      of g_{Z^{'}}~1-2.

PMID- 29570329
TI  - New Methods for Testing Lorentz Invariance with Atomic Systems.
AB  - We describe a broadly applicable experimental proposal to search for the
      violation of local Lorentz invariance (LLI) with atomic systems. The new scheme
      uses dynamic decoupling and can be implemented in current atomic clock
      experiments, with both single ions and arrays of neutral atoms. Moreover, the
      scheme can be performed on systems with no optical transitions, and therefore it
      is also applicable to highly charged ions which exhibit a particularly high
      sensitivity to Lorentz invariance violation. We show the results of an experiment
      measuring the expected signal of this proposal using a two-ion crystal of
      ^{88}Sr^{+} ions. We also carry out a systematic study of the sensitivity of
      highly charged ions to LLI to identify the best candidates for the LLI tests.

PMID- 29570331
TI  - Dynamics of Three-Body Correlations in Quenched Unitary Bose Gases.
AB  - We investigate dynamical three-body correlations in the Bose gas during the
      earliest stages of evolution after a quench to the unitary regime. The
      development of few-body correlations is theoretically observed by determining the
      two- and three-body contacts. We find that the growth of three-body correlations
      is gradual compared to two-body correlations. The three-body contact oscillates
      coherently, and we identify this as a signature of Efimov trimers. We show that
      the growth of three-body correlations depends nontrivially on parameters derived
      from both the density and Efimov physics. These results demonstrate the violation
      of scaling invariance of unitary bosonic systems via the appearance of log
      periodic modulation of three-body correlations.

PMID- 29570330
TI  - Symmorphic Intersecting Nodal Rings in Semiconducting Layers.
AB  - The unique properties of topological semimetals have strongly driven efforts to
      seek for new topological phases and related materials. Here, we identify a
      critical condition for the existence of intersecting nodal rings (INRs) in
      symmorphic crystals, and further classify all possible kinds of INRs which can be
      obtained in the layered semiconductors with Amm2 and Cmmm space group symmetries.
      Several honeycomb structures are suggested to be topological INR semimetals,
      including layered and "hidden" layered structures. Transitions between the three
      types of INRs, named as alpha, beta, and gamma type, can be driven by external
      strains in these structures. The resulting surface states and Landau-level
      structures, more complicated than those resulting from a simple nodal loop, are
      also discussed.

PMID- 29570332
TI  - Quantum Szilard Engine with Attractively Interacting Bosons.
AB  - We show that a quantum Szilard engine containing many bosons with attractive
      interactions enhances the conversion between information and work. Using an ab
      initio approach to the full quantum-mechanical many-body problem, we find that
      the average work output increases significantly for a larger number of bosons.
      The highest overshoot occurs at a finite temperature, demonstrating how thermal
      and quantum effects conspire to enhance the conversion between information and
      work. The predicted effects occur over a broad range of interaction strengths and
      temperatures.

PMID- 29570333
TI  - Ponderomotive Generation and Detection of Attosecond Free-Electron Pulse Trains.
AB  - Atomic motion dynamics during structural changes or chemical reactions have been
      visualized by pico- and femtosecond pulsed electron beams via ultrafast electron
      diffraction and microscopy. Imaging the even faster dynamics of electrons in
      atoms, molecules, and solids requires electron pulses with subfemtosecond
      durations. We demonstrate here the all-optical generation of trains of attosecond
      free-electron pulses. The concept is based on the periodic energy modulation of a
      pulsed electron beam via an inelastic interaction, with the ponderomotive
      potential of an optical traveling wave generated by two femtosecond laser pulses
      at different frequencies in vacuum. The subsequent dispersive propagation leads
      to a compression of the electrons and the formation of ultrashort pulses. The
      longitudinal phase space evolution of the electrons after compression is mapped
      by a second phase-locked interaction. The comparison of measured and calculated
      spectrograms reveals the attosecond temporal structure of the compressed electron
      pulse trains with individual pulse durations of less than 300 as. This technique
      can be utilized for tailoring and initial characterization of suboptical-cycle
      free-electron pulses at high repetition rates for stroboscopic time-resolved
      experiments with subfemtosecond time resolution.

PMID- 29570334
TI  - Imaging Optical Frequencies with 100  MUHz Precision and 1.1  MUm Resolution.
AB  - We implement imaging spectroscopy of the optical clock transition of lattice
      trapped degenerate fermionic Sr in the Mott-insulating regime, combining micron
      spatial resolution with submillihertz spectral precision. We use these tools to
      demonstrate atomic coherence for up to 15 s on the clock transition and reach a
      record frequency precision of 2.5*10^{-19}. We perform the most rapid evaluation
      of trapping light shifts and record a 150 mHz linewidth, the narrowest Rabi line
      shape observed on a coherent optical transition. The important emerging
      capability of combining high-resolution imaging and spectroscopy will improve the
      clock precision, and provide a path towards measuring many-body interactions and
      testing fundamental physics.

PMID- 29570336
TI  - Analytical Computation of Energy-Energy Correlation at Next-to-Leading Order in
      QCD.
AB  - The energy-energy correlation (EEC) between two detectors in e^{+}e^{-}
      annihilation was computed analytically at leading order in QCD almost 40 years
      ago, and numerically at next-to-leading order (NLO) starting in the 1980s. We
      present the first analytical result for the EEC at NLO, which is remarkably
      simple, and facilitates analytical study of the perturbative structure of the
      EEC. We provide the expansion of the EEC in the collinear and back-to-back
      regions through next-to-leading power, information which should aid resummation
      in these regions.

PMID- 29570335
TI  - Spatial Distortion of Vibration Modes via Magnetic Correlation of Impurities.
AB  - Long wavelength vibrational modes in the ferromagnetic semiconductor
      Ga_{0.91}Mn_{0.09}As are investigated using time resolved x-ray diffraction. At
      room temperature, we measure oscillations in the x-ray diffraction intensity
      corresponding to coherent vibrational modes with well-defined wavelengths. When
      the correlation of magnetic impurities sets in, we observe the transition of the
      lattice into a disordered state that does not support coherent modes at large
      wavelengths. Our measurements point toward a magnetically induced broadening of
      long wavelength vibrational modes in momentum space and their quasilocalization
      in the real space. More specifically, long wavelength vibrational modes cannot be
      assigned to a single wavelength but rather should be represented as a
      superposition of plane waves with different wavelengths. Our findings have strong
      implications for the phonon-related processes, especially carrier-phonon and
      phonon-phonon scattering, which govern the electrical conductivity and thermal
      management of semiconductor-based devices.

PMID- 29570338
TI  - 1/2(e^{2}/h) Conductance Plateau without 1D Chiral Majorana Fermions.
AB  - We address the question about the origin of the 1/2(e^{2}/h) conductance plateau
      observed in a recent experiment on an integer quantum Hall (IQH) film covered by
      a superconducting (SC) film. Since one-dimensional (1D) chiral Majorana fermions
      on the edge of the above device can give rise to the half quantized plateau, such
      a plateau is regarded as conclusive evidence for the chiral Majorana fermions.
      However, in this Letter we give another mechanism for the 1/2(e^{2}/h)
      conductance plateau. We find the 1/2(e^{2}/h) conductance plateau to be a general
      feature of a good electric contact between the IQH film and the SC film, and
      cannot distinguish the existence or the nonexistence of 1D chiral Majorana
      fermions. We also find that the contact conductance between a superconductor and
      an IQH edge channel has a non-Ohmic form sigma_{SC-Hall}?V^{2} in the k_{B}T?eV
      limit, if the SC and IQH bulks are fully gapped.

PMID- 29570337
TI  - Millimeter-Wave Beam Scattering by Field-Aligned Blobs in Simple Magnetized
      Toroidal Plasmas.
AB  - The first direct experimental measurements of the scattering of a millimeter-wave
      beam by plasma blobs in a simple magnetized torus are reported. The wavelength of
      the beam is comparable to the characteristic size of the blob. In situ Langmuir
      probe measurements show that fluctuations of the electron density induce
      correlated fluctuations of the transmitted power. A first-principles full-wave
      model, using conditionally sampled 2D electron density profiles, predicts
      fluctuations of the millimeter-wave power that are in agreement with experiments.

PMID- 29570339
TI  - Gouy Phase Radial Mode Sorter for Light: Concepts and Experiments.
AB  - We present an in principle lossless sorter for radial modes of light, using
      accumulated Gouy phases. The experimental setups have been found by a computer
      algorithm, and can be intuitively understood in a geometric way. Together with
      the ability to sort angular-momentum modes, we now have access to the complete
      two-dimensional transverse plane of light. The device can readily be used in
      multiplexing classical information. On a quantum level, it is an analog of the
      Stern-Gerlach experiment-significant for the discussion of fundamental concepts
      in quantum physics. As such, it can be applied in high-dimensional and
      multiphotonic quantum experiments.

PMID- 29570340
TI  - Quartic Anharmonicity of Rattlers and Its Effect on Lattice Thermal Conductivity
      of Clathrates from First Principles.
AB  - We investigate the role of the quartic anharmonicity in the lattice dynamics and
      thermal transport of the type-I clathrate Ba_{8}Ga_{16}Ge_{30} based on ab initio
      self-consistent phonon calculations. We show that the strong quartic
      anharmonicity of rattling guest atoms causes the hardening of vibrational
      frequencies of low-lying optical modes and thereby affects calculated lattice
      thermal conductivities kappa_{L} significantly, resulting in an improved
      agreement with experimental results including the deviation from kappa_{L}?T^{-1}
      at high temperature. Moreover, our static simulations with various different cell
      volumes shows a transition from crystal-like to glasslike kappa_{L} around 20 K.
      Our analyses suggest that the resonance dip of kappa_{L} observed in clathrates
      with large guest free spaces is attributed mainly to the strong three-phonon
      scattering of acoustic modes along with the presence of higher-frequency
      dispersive optical modes.

PMID- 29570341
TI  - Setting Boundaries with Memory: Generation of Topological Boundary States in
      Floquet-Induced Synthetic Crystals.
AB  - When a d-dimensional quantum system is subjected to a periodic drive, it may be
      treated as a (d+1)-dimensional system, where the extra dimension is a synthetic
      one. This approach, however, affords only a limited level of control of the
      effective potential along the synthetic direction. In this work, we introduce a
      new mean for controlling the Floquet synthetic dimension. We show that arbitrary
      potentials, as well as edges in the synthetic dimension, could be introduced
      using a memory component in the system's dynamics. We demonstrate this principle
      by exploring topological edge states propagating normal to synthetic dimensions.
      Such systems may act as an optical isolator which allows the transmission of
      light in a directional way. Also, we suggest an experimental realization of the
      memory effect in spins coupled to nanofabricated Weyl semimetal surface states.

PMID- 29570342
TI  - Search for Dark Matter Annihilation in Galaxy Groups.
AB  - We use 413 weeks of publicly available Fermi Pass 8 gamma-ray data combined with
      recently developed galaxy group catalogs to search for evidence of dark matter
      annihilation in extragalactic halos. In our study, we use luminosity-based mass
      estimates and mass-to-concentration relations to infer the J factors and
      associated uncertainties for hundreds of galaxy groups within a redshift range
      z?0.03. We employ a conservative substructure boost factor model, which only
      enhances the sensitivity by an O(1) factor. No significant evidence for dark
      matter annihilation is found, and we exclude thermal relic cross sections for
      dark matter masses below ~30  GeV to 95% confidence in the bb[over -]
      annihilation channel. These bounds are comparable to those from Milky Way dwarf
      spheroidal satellite galaxies. The results of our analysis increase the tension
      but do not rule out the dark matter interpretation of the Galactic Center excess.
      We provide a catalog of the galaxy groups used in this study and their inferred
      properties, which can be broadly applied to searches for extragalactic dark
      matter.

PMID- 29570343
TI  - In Silico Measurement of Elastic Moduli of Nematic Liquid Crystals.
AB  - Experiments on confined droplets of the nematic liquid crystal 5CB have
      questioned long-established bounds imposed on the elastic free energy of nematic
      systems. This elasticity, which derives from molecular alignment within nematic
      systems, is quantified through a set of moduli which can be difficult to measure
      experimentally and, in some cases, can only be probed indirectly. This is
      particularly true of the surfacelike saddle-splay elastic term, for which the
      available experimental data indicate values on the cusp of stability, often with
      large uncertainties. Here, we demonstrate that all nematic elastic moduli,
      including the saddle-splay elastic constant k_{24}, may be calculated directly
      from atomistic molecular simulations. Importantly, results obtained through in
      silico measurements of the 5CB elastic properties demonstrate unambiguously that
      saddle-splay elasticity alone is unable to describe the observed confined
      morphologies.

PMID- 29570344
TI  - Macroscopic Magnetization Control by Symmetry Breaking of Photoinduced Spin
      Reorientation with Intense Terahertz Magnetic Near Field.
AB  - We exploit an intense terahertz magnetic near field combined with femtosecond
      laser excitation to break the symmetry of photoinduced spin reorientation paths
      in ErFeO_{3}. We succeed in aligning macroscopic magnetization reaching up to 80%
      of total magnetization in the sample to selectable orientations by adjusting the
      time delay between terahertz and optical pump pulses. The spin dynamics are well
      reproduced by equations of motion, including time-dependent magnetic potential.
      We show that the direction of the generated magnetization is determined by the
      transient direction of spin tilting and the magnetic field at the moment of
      photoexcitation.

PMID- 29570345
TI  - Entanglement between a Photonic Time-Bin Qubit and a Collective Atomic Spin
      Excitation.
AB  - Entanglement between light and matter combines the advantage of long distance
      transmission of photonic qubits with the storage and processing capabilities of
      atomic qubits. To distribute photonic states efficiently over long distances
      several schemes to encode qubits have been investigated-time-bin encoding being
      particularly promising due to its robustness against decoherence in optical
      fibers. Here, we demonstrate the generation of entanglement between a photonic
      time-bin qubit and a single collective atomic spin excitation (spin wave) in a
      cold atomic ensemble, followed by the mapping of the atomic qubit onto another
      photonic qubit. A magnetic field that induces a periodic dephasing and rephasing
      of the atomic excitation ensures the temporal distinguishability of the two time
      bins and plays a central role in the entanglement generation. To analyze the
      generated quantum state, we use largely imbalanced Mach-Zehnder interferometers
      to perform projective measurements in different qubit bases and verify the
      entanglement by violating a Clauser-Horne-Shimony-Holt Bell inequality.

PMID- 29570346
TI  - Ultrafast Terahertz Nonlinear Optics of Landau Level Transitions in a Monolayer
      Graphene.
AB  - We investigated the ultrafast terahertz (THz) nonlinearity in a monolayer
      graphene under the strong magnetic field using THz pump-THz probe spectroscopy.
      An ultrafast suppression of the Faraday rotation associated with inter-Landau
      level (LL) transitions is observed, reflecting the Dirac electron character of
      nonequidistant LLs with large transition dipole moments. A drastic modulation of
      electron distribution in LLs is induced by far off-resonant THz pulse excitation
      in the transparent region. Numerical simulation based on the density matrix
      formalism without rotating-wave approximation reproduces the experimental
      results. Our results indicate that the strong light-matter coupling regime is
      realized in graphene, with the Rabi frequency exceeding the carrier wave
      frequency and even the relevant energy scale of the inter-LL transition.

PMID- 29570347
TI  - TREM-1 Response Signatures Common to Expression Profiles of Both Asthma Affection
      and Asthma Control.

PMID- 29570348
TI  - For myosin light chain phosphatase, a very small subunit can make very big
      differences in the heart.

PMID- 29570349
TI  - A microRNA's journey to the center of the mitochondria.
AB  - MicroRNAs (miRNAs) are known as the master regulators of gene expression, and for
      the last two decades our knowledge of their functional reach keeps expanding.
      Recent studies have shown that a miRNA's role in regulation extends to
      extracellular and intracellular organelles. Several studies have shown a role for
      miRNA in regulating the mitochondrial genome in normal and disease conditions.
      Mitochondrial dysfunction occurs in many human pathologies, such as
      cardiovascular disease, diabetes, cancer, and neurological diseases. These
      studies have shed some light on regulation of the mitochondrial genome as well as
      helped to explain the role of miRNA in altering mitochondrial function and the
      ensuing effects on cells. Although the field has grown in recent years, many
      questions still remain. For example, little is known about how nuclear-encoded
      miRNAs translocate to the mitochondrial matrix. Knowledge of the mechanisms of
      miRNA transport into the mitochondrial matrix is likely to provide important
      insights into our understanding of disease pathophysiology and could represent
      new targets for therapeutic intervention. For this review, our focus will be on
      the role of a subset of miRNAs, known as MitomiR, in mitochondrial function. We
      also discuss the potential mechanisms used by these nuclear-encoded miRNAs for
      import into the mitochondrial compartment. Listen to this article's corresponding
      podcast at http://ajpheart.podbean.com/e/microrna-translocation-into-the
      mitochondria/ .

PMID- 29570350
TI  - Volumetric Capnography for Noninvasive Monitoring of Acute Respiratory Distress
      Syndrome.

PMID- 29570351
TI  - Erratum.

PMID- 29570352
TI  - Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and
      Implications for Drug Design.
AB  - Genetic information is translated into proteins by the ribosome. Structural
      studies of the ribosome and of its complexes with factors and inhibitors have
      provided invaluable information on the mechanism of protein synthesis. Ribosome
      inhibitors are among the most successful antimicrobial drugs and constitute more
      than half of all medicines used to treat infections. However, bacterial
      infections are becoming increasingly difficult to treat because the microbes have
      developed resistance to the most effective antibiotics, creating a major public
      health care threat. This has spurred a renewed interest in structure-function
      studies of protein synthesis inhibitors, and in few cases, compounds have been
      developed into potent therapeutic agents against drug-resistant pathogens. In
      this review, we describe the modes of action of many ribosome-targeting
      antibiotics, highlight the major resistance mechanisms developed by pathogenic
      bacteria, and discuss recent advances in structure-assisted design of new
      molecules.

PMID- 29570353
TI  - Dynamics of Bacterial Gene Regulatory Networks.
AB  - The ability of bacterial cells to adjust their gene expression program in
      response to environmental perturbation is often critical for their survival.
      Recent experimental advances allowing us to quantitatively record gene expression
      dynamics in single cells and in populations coupled with mathematical modeling
      enable mechanistic understanding on how these responses are shaped by the
      underlying regulatory networks. Here, we review how the combination of local and
      global factors affect dynamical responses of gene regulatory networks. Our goal
      is to discuss the general principles that allow extrapolation from a few model
      bacteria to less understood microbes. We emphasize that, in addition to well
      studied effects of network architecture, network dynamics are shaped by global
      pleiotropic effects and cell physiology.

PMID- 29570354
TI  - Predictors of Clinical Outcomes After Hip Arthroscopy: A Prospective Analysis of
      1038 Patients With 2-Year Follow-up.
AB  - BACKGROUND: As hip arthroscopy has expanded in popularity and volume, more
      information is needed about indications for the procedure and the predictive
      factors of clinical outcomes. PURPOSE: To evaluate clinical outcomes of hip
      arthroscopy in a prospective study and to analyze the cohort to identify factors
      that are predictive of improvement. STUDY DESIGN: Case-control study; Level of
      evidence, 3. METHODS: Data were collected prospectively on all patients
      undergoing hip arthroscopy between February 2008 and June 2012. We included all
      patients undergoing hip arthroscopy who agreed to participate and who completed 4
      patient-reported outcome (PRO) instruments at a minimum 2-year follow-up: the
      modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome
      Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific
      Subscale. The NAHS was selected as our primary outcome instrument. All patients
      with any previous hip conditions were excluded. We analyzed 34 preoperative and
      intraoperative variables using bivariate and multivariate analyses compared with
      NAHS. RESULTS: The cohort consisted of 1038 patients with a mean follow-up of
      30.1 months (range, 24.0-61.2 months). Mean age was 36.4 years (range, 13.2-76.4
      years). All postoperative PRO scores showed significant improvement ( P < .001)
      at 2 years compared with preoperative scores. Bivariate analysis identified 15
      variables (7 categorical and 8 continuous) and multivariate analysis identified
      10 variables that were predictive of 2-year postoperative NAHS. Preoperative
      NAHS, preoperative HOS-ADL, preoperative mHHS, age, duration of symptoms, body
      mass index (BMI), and revision hip arthroscopy were identified as predictive
      factors in both bivariate and multivariate analyses. The predictive value of
      preoperative NAHS was accentuated for patients with higher BMI. CONCLUSION: This
      study reports favorable clinical outcomes in the largest cohort of hip
      arthroscopies with a minimum 2-year follow-up in the literature to date. Factors
      identified as predictive in both bivariate and multivariate analyses included
      preoperative NAHS, HOS-ADL, and mHHS; age; duration of symptoms; BMI; and
      revision hip arthroscopy. These predictive factors may be useful to the clinician
      in determining prognosis and operative indications for hip arthroscopy.

PMID- 29570355
TI  - Findings from an Assessment and Inventory of a Regional, Decentralized Stockpile.
AB  - Stockpiles can aid with healthcare surge that occurs after a disaster, and
      experts recommend that these caches be assessed at least annually to ensure
      supply integrity. The purpose of this study was to assess a regional stockpile to
      determine its viability and readiness. An assessment was performed in the summer
      and fall of 2016 on a regionally funded stockpile that was decentralized through
      a regional network of 15 local hospitals. Each supply was assessed to determine
      whether the correct amount was present, if it was in a safe and usable condition
      (ie, deployable), and whether it had expired. Stockpiled materials were
      categorized by the type of supply or equipment for analysis. The percent of
      deployable materials was calculated for each item, each category of supplies, and
      for the entire cache. Almost all sites (93.3%, n = 14) reported that they
      inventory their cache at least once a year. On average, 60.1% of each site's
      cache materials were present and deployable (range: 22.1%-87.5%). The best
      maintained supplies included personal protective equipment (79.4% deployable) and
      general medical supplies (73.5% deployable). Decontamination equipment and
      pediatric supplies had the lowest percentages of deployability (29.0% and 37.7%,
      respectively). Although almost all sites claimed to assess the stockpile
      annually, results from this study indicate that almost half of the supplies are
      either missing or in an unusable condition. This not only represents wasted
      resources, but it could also hinder disaster response, leading to increased
      morbidity and mortality. Facilities may need to invest in infrastructure to
      maintain stockpiled materials after purchase to ensure viability.

PMID- 29570356
TI  - Crystal Engineering for Catalysis.
AB  - Crystal engineering relies upon the ability to predictively control
      intermolecular interactions during the assembly of crystalline materials in a
      manner that leads to a desired (and predetermined) set of properties. Economics,
      scalability, and ease of design must be leveraged with techniques that manipulate
      the thermodynamics and kinetics of crystal nucleation and growth. It is often
      challenging to exact simultaneous control over multiple physicochemical
      properties, such as crystal size, habit, chirality, polymorph, and composition.
      Engineered materials often rely upon postsynthesis (top-down) processes to
      introduce properties that would otherwise be challenging to attain through direct
      (bottom-up) approaches. We discuss the application of crystal engineering to
      heterogeneous catalysts with a focus on four general themes: ( a) tailored
      nanocrystal size, ( b) controlled environments surrounding active sites, ( c)
      tuned morphology with well-defined facets, and ( d) hierarchical materials with
      disparate pore size and active site distributions. We focus on nonporous
      materials, including metals and metal oxides, and two classes of porous
      materials: zeolites and metal organic frameworks. We review novel synthesis
      methods involving synergistic experimental and computational design approaches,
      the challenges facing catalyst development, and opportunities for future
      advancement in crystal engineering.

PMID- 29570357
TI  - Single- to Few-Layered, Graphene-Based Separation Membranes.
AB  - Two-dimensional, graphene-based materials have attracted great attention as a new
      membrane building block, primarily owing to their potential to make the thinnest
      possible membranes and thus provide the highest permeance for effective sieving,
      assuming comparable porosity to conventional membranes and uniform molecular
      sized pores. However, a great challenge exists to fabricate large-area, single
      layered graphene or graphene oxide (GO) membranes that have negligible undesired
      transport pathways, such as grain boundaries, tears, and cracks. Therefore, model
      systems, such as a single flake or nanochannels between graphene or GO flakes,
      have been studied via both simulations and experiments to explore the transport
      mechanisms and separation potential of graphene-based membranes. This article
      critically reviews literature related to single- to few-layered graphene and GO
      membranes, from material synthesis and characteristics, fundamental membrane
      structures, and transport mechanisms to potential separation applications.
      Knowledge gaps between science and engineering in this new field and future
      opportunities for practical separation applications are also discussed.

PMID- 29570358
TI  - Long Noncoding RNA LINC00958 Accelerates Gliomagenesis Through Regulating miR
      203/CDK2.
AB  - Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play crucial
      roles in various biological processes, including glioma. However, the underlying
      mechanism of lncRNAs in gliomagenesis is still ambiguous. In this study, we aim
      to investigate the role of long intergenic noncoding RNA 00958 (LINC00958) in the
      tumorigenesis of glioma. Results revealed that LINC00958 was significantly
      upregulated in glioma tissues and cell lines compared with that of adjacent
      normal brain tissues and normal human astrocytes. Moreover, the ectopic
      overexpression of LINC00958 was correlated with poor prognosis of glioma
      patients. Loss-of-function experiments indicated that LINC00958 knockdown
      suppressed glioma cell proliferation, invasion, and induced cycle arrest at G0/G1
      phase in vitro, and inhibited tumor growth in vivo. Bioinformatics programs and
      luciferase reporter assay revealed that miR-203 shared complementary binding
      sites with both 3'-untranslated region of LINC00958 and CDK2. In summary, our
      study concludes that LINC00958 acts as an oncogenic gene in the gliomagenesis
      through miR-203-CDK2 regulation, providing a novel insight into glioma
      tumorigenesis.

PMID- 29570359
TI  - Progestogens and venous thromboembolism in menopausal women: an updated oral
      versus transdermal estrogen meta-analysis.
AB  - Postmenopausal hormone therapy (HT) is a modifiable risk factor for venous
      thromboembolism (VTE). While the route of estrogen administration is now well
      recognized as an important determinant of VTE risk, there is also increasing
      evidence that progestogens may modulate the estrogen-related VTE risk. This
      review updates previous meta-analyses of VTE risk in HT users, focusing on the
      route of estrogen administration, hormonal regimen and progestogen type. Among
      women using estrogen-only preparations, oral but not transdermal preparations
      increased VTE risk (relative risk (RR) 1.48, 95% confidence interval (CI) 1.39
      1.58; RR 0.97, 95% CI 0.87-1.09, respectively). In women using opposed estrogen,
      results were highly heterogeneous due to important differences between the
      molecules of progestogen. In transdermal estrogen users, there was no change in
      VTE risk in women using micronized progesterone (RR 0.93, 95% CI 0.65-1.33),
      whereas norpregnane derivatives were associated with increased VTE risk (RR 2.42,
      95% CI 1.84-3.18). Among women using opposed oral estrogen, there was higher VTE
      risk in women using medroxyprogesterone acetate (RR 2.77, 95% CI 2.33-3.30) than
      in those using other progestins. These clinical findings, together with
      consistent biological data, emphasize the safety advantage of transdermal
      estrogen combined with progesterone and support the current evidence-based
      recommendations on HT, especially in women at high VTE risk.

PMID- 29570360
TI  - Interfacing Cells with Vertical Nanoscale Devices: Applications and
      Characterization.
AB  - Measurements of the intracellular state of mammalian cells often require probes
      or molecules to breach the tightly regulated cell membrane. Mammalian cells have
      been shown to grow well on vertical nanoscale structures in vitro, going out of
      their way to reach and tightly wrap the structures. A great deal of research has
      taken advantage of this interaction to bring probes close to the interface or
      deliver molecules with increased efficiency or ease. In turn, techniques have
      been developed to characterize this interface. Here, we endeavor to survey this
      research with an emphasis on the interface as driven by cellular mechanisms.

PMID- 29570361
TI  - Optimizing the flavanone core toward new selective nitrogen-containing modulators
      of ABC transporters.
AB  - AIM: Naringenin (1), isolated in large amount from the aerial parts of Euphorbia
      pedroi, was chemically derivatized to yield 18 imine derivatives (2-19) and three
      alkylated derivatives through a Mannich-type reaction (20-22) that were tested as
      multidrug resistance (MDR) reversers in cancer cells. Results/methodology: While
      hydrazone (2-4) and azine (5-13) derivatives showed an improvement in their MDR
      reversal activities against the breast cancer resistance protein, carbohydrazides
      14-19 revealed an enhancement in MDR reversal activity toward the multidrug
      resistance protein 1. CONCLUSION: The observed activities, together with
      pharmacophoric analysis and molecular docking studies, identified the spatial
      orientation of the substituents as a key structural feature toward a possible
      mechanism by which naringenin derivatives may reverse MDR in cancer.

PMID- 29570362
TI  - Verbal test of practical judgment (VPJ): a new test of judgment that predicts
      functional skills for older adults.
AB  - OBJECTIVES: The clinical assessment of older adults' judgment is important for
      mitigating safety risks that often precipitate loss of independence. Our national
      survey of geriatric healthcare providers (N = 496; M years of experience = 17.11
      +/- 10.60) indicated that formal judgment tests are underutilized in clinical
      practice. We developed the Verbal Test of Practical Judgment (VPJ) as a new test
      of judgment for older adults intended to identify difficulty performing
      instrumental activities of daily living (IADL). METHOD: In two prospective
      studies, participants were long-term care facility residents (age >= 50) in
      Maryland, USA (Study 1, N = 51; Study 2, N = 110) referred to licensed
      psychologists for neuro-cognitive and mood evaluation by facility attending
      physicians. Psychometric analyses were performed to examine the construct
      validity of the VPJ. RESULTS: The VPJ evidenced adequate reliability and strong
      construct validity across both studies. Receiver operating characteristic
      analysis yielded an optimal VPJ cut score for identifying impaired judgment. The
      VPJ significantly predicted IADL performance beyond clinician and participant
      ratings. CONCLUSION: The VPJ appears to be a valid tool for assessing judgment
      among older adults with suspected cognitive impairment. VPJ score inferences can
      inform clinicians on the odds of requiring assistance for specific IADLs.

PMID- 29570363
TI  - Pharmacist Views on Alternative Methods for Antiviral Distribution and Dispensing
      During an Influenza Pandemic.
AB  - Antiviral drugs are likely to be a frontline countermeasure needed to minimize
      disease impact during an influenza pandemic. As part of pandemic influenza
      preparedness efforts, the Centers for Disease Control and Prevention, in
      coordination with state health departments, has plans in place to distribute and
      dispense antiviral drugs from public stockpiles. These plans are currently under
      review and include evaluation of the benefits of commercial distribution and
      dispensing through community pharmacies. To ensure this alternative distribution
      and dispensing system is viable, it is critical to assess pharmacist
      acceptability and to understand the pharmacist perspective on dispensing these
      antivirals during a response. In this study, we examine community pharmacist
      reactions to the proposed alternative antiviral distribution and dispensing
      system using a nationally representative survey of pharmacists. Overall,
      pharmacists were highly receptive to this alternative system and voiced a
      willingness to participate personally, and most thought their own pharmacy would
      participate in such an effort. This was true across pharmacists with different
      personal and professional backgrounds, as well as those in different pharmacy
      settings. However, sizable shares of pharmacists said they were worried about
      facing shortages of the antivirals, the risk of exposure to disease for
      themselves and their families, managing their usual patients who need their
      prescriptions filled for medications other than antivirals, keeping order in the
      pharmacy, and potential liability concerns. These findings should be interpreted
      as an indication of acceptability of the concept, encouragement for the next
      steps in alternative distribution and dispensing system design, and a guide to
      potential barriers that may need to be addressed proactively.

PMID- 29570364
TI  - Protein Quality Control in the Endoplasmic Reticulum of Plants.
AB  - The endoplasmic reticulum (ER) is the site of maturation for roughly one-third of
      all cellular proteins. ER-resident molecular chaperones and folding catalysts
      promote folding and assembly in a diverse set of newly synthesized proteins.
      Because these processes are error-prone, all eukaryotic cells have a quality
      control system in place that constantly monitors the proteins and decides their
      fate. Proteins with potentially harmful nonnative conformations are subjected to
      assisted folding or degraded. Persistent folding-defective proteins are
      distinguished from folding intermediates and targeted for degradation by a
      specific process involving clearance from the ER. Although the basic principles
      of these processes appear conserved from yeast to animals and plants, there are
      distinct differences in the ER-associated degradation of misfolded glycoproteins.
      The general importance of ER quality-control events is underscored by their
      involvement in the biogenesis of diverse cell surface receptors and their crucial
      maintenance of protein homeostasis under diverse stress conditions.

PMID- 29570365
TI  - Nitrate Transport, Signaling, and Use Efficiency.
AB  - Nitrogen accounts for approximately 60% of the fertilizer consumed each year;
      thus, it represents one of the major input costs for most nonlegume crops.
      Nitrate is one of the two major forms of nitrogen that plants acquire from the
      soil. Mechanistic insights into nitrate transport and signaling have enabled new
      strategies for enhancing nitrogen utilization efficiency, for lowering input
      costs for farming, and, more importantly, for alleviating environmental impacts
      (e.g., eutrophication and production of the greenhouse gas N2O). Over the past
      decade, significant progress has been made in understanding how nitrate is
      acquired from the surroundings, how it is efficiently distributed into different
      plant tissues in response to environmental changes, how nitrate signaling is
      perceived and transmitted, and how shoot and root nitrogen status is
      communicated. Several key components of these processes have proven to be novel
      tools for enhancing nitrate- and nitrogen-use efficiency. In this review, we
      focus on the roles of NRT1 and NRT2 in nitrate uptake and nitrate allocation
      among different tissues; we describe the functions of the transceptor NRT1.1,
      transcription factors, and small signaling peptides in nitrate signaling and
      tissue communication; and we compile the new strategies for improving nitrogen
      use efficiency.

PMID- 29570314
TI  - D-Meson Azimuthal Anisotropy in Midcentral Pb-Pb Collisions at sqrt[s]_{NN}=5.02 
      TeV.
AB  - The azimuthal anisotropy coefficient v_{2} of prompt D^{0}, D^{+}, D^{*+}, and
      D_{s}^{+} mesons was measured in midcentral (30%-50% centrality class) Pb-Pb
      collisions at a center-of-mass energy per nucleon pair sqrt[s_{NN}]=5.02  TeV,
      with the ALICE detector at the LHC. The D mesons were reconstructed via their
      hadronic decays at midrapidity, |y|<0.8, in the transverse momentum interval
      1<p_{T}<24  GeV/c. The measured D-meson v_{2} has similar values as that of
      charged pions. The D_{s}^{+} v_{2}, measured for the first time, is found to be
      compatible with that of nonstrange D mesons. The measurements are compared with
      theoretical calculations of charm-quark transport in a hydrodynamically expanding
      medium and have the potential to constrain medium parameters.

PMID- 29570366
TI  - Therapeutic approach for patients with venous thromboembolism attended in
      emergency departments during routine clinical practice: the EDITH study.
AB  - AIM: To analyze treatment at discharge/follow-up of patients diagnosed with
      venous thromboembolism (VTE) in the emergency department (ED). MATERIALS &
      METHODS: Ambispective study (50 Spanish centers) of consecutive patients (October
      December 2014) with VTE diagnosed in ED. RESULTS: VTE was diagnosed in 775
      patients (295 pulmonary embolism [PE] without deep vein thrombosis [DVT], 389 DVT
      without PE and 91 PE + DVT); 95.5% received anticoagulants (90.7% low-molecular
      weight heparin [LMWH], 4% LMWH + vitamin K antagonists and <1% direct oral
      anticoagulants). Overall, 23.3% were discharged from ED and 74.5% hospitalized
      (98.6% with PE and 50.4% with DVT). After discharge/90/180 days, 43.6/21.0/13.5%
      were taking LMWH, with similar rates in nononcologic patients. CONCLUSION: There
      is a poor adherence to international guidelines in management of VTE patients in
      Spain.

PMID- 29570367
TI  - Initial Experience of Tomosynthesis-Guided Vacuum-Assisted Biopsies of
      Tomosynthesis-Detected (2D Mammography and Ultrasound Occult) Architectural
      Distortions.
AB  - OBJECTIVE: As experience and aptitude in digital breast tomosynthesis (DBT) have
      increased, radiologists are seeing more areas of architectural distortion (AD) on
      DBT images compared with standard 2D mammograms. The purpose of this study is to
      report our experience using tomosynthesis-guided vacuum-assisted biopsies (VABs)
      for ADs that were occult at 2D mammography and ultrasound and to analyze the
      positive predictive value for malignancy. MATERIALS AND METHODS: We performed a
      retrospective review of 34 DBT-detected ADs that were occult at mammography and
      ultrasound. RESULTS: We found a positive predictive value of 26% (nine
      malignancies in 34 lesions). Eight of the malignancies were invasive and one was
      ductal carcinoma in situ. The invasive cancers were grade 1 (4/8; 50%), grade 2
      (2/8; 25%), or grade 3 (1/8; 13%); information about one invasive cancer was not
      available. The mean size of the invasive cancers at pathologic examination was
      7.5 mm (range, 6-30 mm). CONCLUSION: Tomosynthesis-guided VAB is a feasible
      method to sample ADs that are occult at 2D mammography and ultrasound.
      Tomosynthesis-guided VAB is a minimally invasive method that detected a
      significant number of carcinomas, most of which were grade 1 cancers. Further
      studies are needed.

PMID- 29570370
TI  - Screening Mammography and Digital Breast Tomosynthesis: Utilization Updates.
AB  - OBJECTIVE: There have been many recent developments in breast imaging, including
      the 2009 revision of the U.S. Preventive Services Task Force's breast cancer
      screening guidelines and the approval of digital breast tomosynthesis (DBT) for
      clinical use in 2011. The objective of this study is to evaluate screening
      mammography utilization trends among the Medicare population from 2005 to 2015
      and examine the volume of DBT studies performed in 2015, the first year for which
      procedural billing codes for DBT are available. MATERIALS AND METHODS: We
      reviewed national Medicare Part B Physician/Supplier Procedure Summary master
      files from 2005 to 2015, to determine the annual utilization rate of screening
      mammography on the basis of procedure codes used for film-screen and digital
      screening mammography. We also used the Physician/Supplier Procedure Summary
      master files to determine the volume of screening and diagnostic DBT studies
      performed in 2015. RESULTS: The utilization rate of screening mammography per
      1000 women in the Medicare fee-for-service population increased gradually every
      year, from 311.5 examinations in 2005 to a peak of 322.9 examinations in 2009,
      representing a compound annual growth rate of 0.9%. In 2010, the utilization rate
      abruptly decreased by 4.3% to 309.2 examinations, and it has not since recovered
      to pre-2010 levels. In 2015, 18.9% of screening and 16.2% of diagnostic digital
      mammography examinations included DBT as an add-on procedure. CONCLUSION: In
      contrast to the annual increase in screening mammography utilization from 2005 to
      2009, an abrupt sustained decline in screening occurred beginning in 2010,
      coinciding with the release of U.S. Preventive Services Task Force
      recommendations. DBT utilization was somewhat limited in 2015, occurring in
      conjunction with less than 20% of digital mammography examinations.

PMID- 29570371
TI  - Introduction to Imaging of Penile Prostheses: A Primer for the Radiologist.
AB  - OBJECTIVE: The purpose of this article is to provide radiologists with an
      introduction to the imaging appearances of various types of penile prostheses and
      discuss imaging pitfalls. CONCLUSION: Two major types of penile prostheses
      currently are in use: malleable penile prostheses and inflatable penile
      prostheses. Sonography is useful in the assessment of the pelvic reservoir and
      scrotal pump. MRI helps in the complete evaluation of all the prosthetic
      components, making it a "one-stop shop" imaging technique.

PMID- 29570369
TI  - Implementation of Size-Dependent Local Diagnostic Reference Levels for CT
      Angiography.
AB  - OBJECTIVE: Diagnostic reference levels (DRLs) are established for standard-sized
      patients; however, patient dose in CT depends on patient size. The purpose of
      this study was to introduce a method for setting size-dependent local diagnostic
      reference levels (LDRLs) and to evaluate these LDRLs in comparison with size
      independent LDRLs and with respect to image quality. MATERIALS AND METHODS: One
      hundred eighty-four aortic CT angiography (CTA) examinations performed on either
      a second-generation or third-generation dual-source CT scanner were included; we
      refer to the second-generation dual-source CT scanner as "CT1" and the third
      generation dual-source CT scanner as "CT2." The volume CT dose index (CTDIvol)
      and patient diameter (i.e., the water-equivalent diameter) were retrieved by dose
      monitoring software. Size-dependent DRLs based on a linear regression of the
      CTDIvol versus patient size were set by scanner type. Size-independent DRLs were
      set by the 5th and 95th percentiles of the CTDIvol values. Objective image
      quality was assessed using the signal-to-noise ratio (SNR), and subjective image
      quality was assessed using a 4-point Likert scale. RESULTS: The CTDIvol depended
      on patient size and scanner type (R2 = 0.72 and 0.78, respectively; slope = 0.05
      and 0.02 mGy/mm; p < 0.001). Of the outliers identified by size-independent DRLs,
      30% (CT1) and 67% (CT2) were adequately dosed when considering patient size.
      Alternatively, 30% (CT1) and 70% (CT2) of the outliers found with size-dependent
      DRLs were not identified using size-independent DRLs. A negative correlation was
      found between SNR and CTDIvol (R2 = 0.36 for CT1 and 0.45 for CT2). However, all
      outliers had a subjective image quality score of sufficient or better.
      CONCLUSION: We introduce a method for setting size-dependent LDRLs in CTA. Size
      dependent LDRLs are relevant for assessing the appropriateness of the radiation
      dose for an individual patient on a specific CT scanner.

PMID- 29570368
TI  - Morel-Lavallee Lesions of the Knee: MRI Findings Compared With Cadaveric Study
      Findings.
AB  - OBJECTIVE: The purpose of this study is to describe the MRI findings and
      treatment decisions and outcome for Morel-Lavallee lesions (MLLs) of the knee and
      to investigate whether evidence exists to support an increased frequency of such
      lesions on the medial or lateral side by performing a cadaveric experiment.
      MATERIALS AND METHODS: In a 4-year period, 24 MRI studies of 24 consecutive
      patients (16 male patients and eight female patients) with knee MLLs were
      retrospectively reviewed. Patient demographic characteristics, treatment
      decisions and outcome, and associated injuries were recorded. The location of the
      MLL was categorized as medial, lateral, or global. Lesions were categorized
      according to an established MRI classification. During the cadaveric experiment,
      the compartmental pressures of the medial or lateral aspect of the knee were
      monitored in 20 cadaveric knees. The chi-square test, t test, and Pearson
      correlation were used for statistical analysis. RESULTS: MLLs were located
      medially in 16 patients, laterally in two patients, and globally in six patients.
      The medial location was significantly more common than a lateral or global
      location (p < 0.05). MLLs were classified as type I in 14 patients, type II in
      eight patients, and type III in two patients. MRI type was correlated with the
      chronicity of injury (r2 = 0.614; p = 0.0014). Fractures were the most common
      associated injuries, occurring in seven of 24 patients. In 17 patients, all of
      whom had conservatively treated type I or type II lesions, complete resolution of
      the MLL occurred. The maximum compartmental pressures were significantly higher
      on the lateral side than on the medial side (p < 0.0001). CONCLUSION: Knee MLLs
      have a predilection for the medial side, which may be attributed to the lower
      resistance in this location, and they have variable patterns on MRI, which
      correlate with chronicity. Conservative treatment of type I and II lesions seems
      effective.

PMID- 29570372
TI  - Acute Fracture of the Anterior Process of Calcaneus: Does It Herald a More
      Advanced Injury to Chopart Joint?
AB  - OBJECTIVE: Injuries at the calcaneocuboid and talonavicular joint have been
      described as two distinct, unrelated entities in the radiology literature. Our
      purpose was to assess the coexistence of these injuries using radiography and MRI
      and to correlate our findings with radiologic and clinical diagnoses. MATERIALS
      AND METHODS: Twenty-one patients with injury at the anterior calcaneal process on
      radiographs or MR images were retrospectively assessed for concomitant injury at
      the talonavicular joint. Radiologic and clinical diagnoses and treatment were
      documented. McNemar and kappa statistics were calculated; p values < 0.05 were
      considered statistically significant. RESULTS: Radiographic and MRI rates of
      detection of injuries across the Chopart joint were statistically different.
      Calcaneocuboid avulsion fractures were evident on 48% of radiographs and 100% of
      MR images (p = 0.001). Talonavicular joint injuries were evident on 38% of
      radiographs and 76% of MR images (p = 0.008). Concomitant injury at both joints
      was evident on 14% of radiographs and 76% of MR images (p < 0.0001). Interrater
      agreement was 0.488-0.637 and 0.286-0.364 for talonavicular and 0.144-0.538 and
      0.976-1 for calcaneocuboid injuries on radiography and MRI, respectively. Sixty
      percent of calcaneocuboid fractures were prospectively missed on radiography
      (none on MRI), whereas 38% and 25% of talonavicular findings were missed on
      radiography and MRI, respectively. Sixty percent of injuries were clinically
      misdiagnosed as ankle sprains. Chopart joint injury was never mentioned in
      prospective clinical or imaging diagnoses. CONCLUSION: Calcaneocuboid and
      talonavicular injuries commonly coexist. Radiographs underestimate severity of
      injury; MR images show more subtle abnormalities. Lack of mention of Chopart
      joint injury clinically and on imaging reports underlies the need for greater
      familiarity with this entity.

PMID- 29570373
TI  - Comparison of DWI Methods in the Pediatric Brain: PROPELLER Turbo Spin-Echo
      Imaging Versus Readout-Segmented Echo-Planar Imaging Versus Single-Shot Echo
      Planar Imaging.
AB  - OBJECTIVE: The purpose of this study is to compare DWI for pediatric brain
      evaluation using single-shot echo-planar imaging (EPI), periodically rotated
      overlapping parallel lines with enhanced reconstruction (Blade), and readout
      segmented EPI (Resolve). MATERIALS AND METHODS: Blade, Resolve, and single-shot
      EPI were performed for 27 pediatric patients (median age, 9 years), and three
      datasets were independently reviewed by two radiologists. Qualitative analyses
      were performed for perceptive coarseness, image distortion, susceptibility
      related changes, motion artifacts, and lesion conspicuity using a 5-point Likert
      scale. Quantitative analyses were conducted for spatial distortion and signal
      uniformity of each sequence. RESULTS: Mean scores were 2.13, 3.17, and 3.76 for
      perceptive coarseness; 4.85, 3.96, and 2.19 for image distortion; 4.76, 3.96, and
      2.30 for susceptibility-related change; 4.96, 3.83, and 4.69 for motion
      artifacts; and 2.71, 3.75, and 1.92 for lesion conspicuity, for Blade, Resolve,
      and single-shot EPI, respectively. Blade and Resolve showed better quality than
      did single-shot EPI for image distortion, susceptibility-related changes, and
      lesion conspicuity. Blade showed less image distortion, fewer susceptibility
      related changes, and fewer motion artifacts than did Resolve, whereas lesion
      conspicuity was better with Resolve. Blade showed increased signal variation
      compared with Resolve and single-shot EPI (coefficients of variation were 0.10,
      0.08, and 0.05 for lateral ventricle; 0.13, 0.09, and 0.05 for centrum semiovale;
      and 0.16, 0.09, and 0.06 for pons in Blade, Resolve, and single-shot EPI,
      respectively). CONCLUSION: DWI with Resolve or Blade yields better quality
      regarding distortion, susceptibility-related changes, and lesion conspicuity,
      compared with single-shot EPI. Blade is less susceptible to motion artifacts than
      is Resolve, whereas Resolve yields less noise and better lesion conspicuity than
      does Blade.

PMID- 29570374
TI  - Shear Wave Elastography as a Quantitative Biomarker of Clinically Significant
      Portal Hypertension: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To qualify shear wave elastography (SWE) as a biomarker for clinically
      significant portal hypertension (CSPH) beyond proof of concept, we aimed to
      accumulate and summarize the current evidence through systematic review and meta
      analysis. MATERIALS AND METHODS: A computerized literature search was performed
      to identify studies from MEDLINE and EMBASE up to February 9, 2017. Studies on
      the diagnostic performance of liver stiffness measurements using SWE for CSPH
      with hepatic venous pressure gradient (HVPG) as the reference standard were
      included. Various aspects of SWE were comprehensively assessed. The summary
      diagnostic performance of SWE for the diagnosis of CSPH and the summary
      correlation coefficient between liver stiffness measured using SWE and HVPG were
      evaluated through a meta-analysis. RESULTS: Nine articles (including 746
      patients) were retrieved. The diagnostic performance of SWE for the diagnosis of
      CSPH was fairly good, with a summary sensitivity of 85% (95% CI, 75-91%; I2 =
      78.56%) and summary specificity of 85% (95% CI, 77-90%; I2 = 0%); the area under
      the ROC curve was 0.88 (95% CI, 0.85-0.91). The summary correlation coefficient
      between liver stiffness and HVPG measurements was 0.741 (95% CI, 0.658-0.825; I2
      = 0%). These results support the value of SWE as a diagnostic biomarker for CSPH.
      However, there was significant heterogeneity in the imaging devices, protocols,
      liver stiffness measurement methods, and cutoff values used, which suggests that
      standardization is required. CONCLUSION: The consistent evidence favoring SWE as
      a biomarker for CSPH should be considered in the biomarker qualification process
      and management of patients with CSPH.

PMID- 29570375
TI  - Improving the Quality of MRI Reports of Preoperative Patients With Rectal Cancer:
      Effect of National Guidelines and Structured Reporting.
AB  - OBJECTIVE: Since the implementation of new guidelines for rectal cancer in The
      Netherlands in April 2014, clinical stage as seen at preoperative MRI indicates
      whether neoadjuvant therapy is necessary before rectal cancer surgery. Therefore,
      the importance of correct MRI interpretation has increased. The aim of this study
      was to evaluate the completeness of MRI reports of rectal cancer and the effect
      of implementation of the new guidelines and standardized reporting on the
      completeness of these reports. MATERIALS AND METHODS: Data were collected from
      all patients who consecutively underwent rectal cancer surgery at one hospital
      between January 2011 and July 2017. Data were extracted from electronic patient
      records. RESULTS: The study included 492 MRI examinations. Before implementation
      of the new guidelines, a median of 4 of 10 items (interquartile range [IQR], 3-6
      items) were described in each MRI report. After implementation of the new
      guidelines, the number of items described improved significantly (median, 7
      items; IQR, 6-8 items; p < 0.001). Implementation of a standardized report led to
      further significant improvement (median, 9 items; IQR, 9-10 items; p < 0.001).
      The items scored most frequently were distance between the tumor and the anal
      verge (85.6%) and length of the tumor (87.6%). The items scored least were
      presence or absence of extramural venous invasion (21.1%) and morphologic
      features of the tumor (24.6%). CONCLUSION: Implementation of a standardized
      protocol and a standardized reporting system for MRI in preoperative staging of
      rectal cancer results in a more complete MRI report.

PMID- 29570376
TI  - Best Protocol for Combined Contrast-Enhanced Thoracic and Abdominal CT for Lung
      Cancer: A Single-Institution Randomized Crossover Clinical Trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the superiority of either of
      two protocols for combined contrast-enhanced thoracic and abdominal CT of
      patients with lung cancer by comparing contrast enhancement, contrast-related
      artifacts, image quality, and radiation dose. SUBJECTS AND METHODS: In this
      randomized controlled crossover clinical trial, 77 patients who underwent 203 CT
      examinations were enrolled. All patients underwent at least two examinations
      performed with both protocols. Protocol A consisted of two acquisitions: one 35
      second delayed CT acquisition for the chest followed by a 70-second delayed
      abdominal acquisition. Protocol B was a single 60-second delayed acquisition
      covering the chest and the abdomen. Attenuation and noise of the aorta, pulmonary
      artery, and liver were measured. Contrast-related artifacts, mediastinal lymph
      node visualization, liver enhancement, and noise were visually scored. Dose
      length product was recorded. Statistical analysis was performed by t and chi
      square tests and kappa statistics. RESULTS: Contrast-related artifacts were more
      severe at all evaluated levels, and visualization of lymph node regions was
      statistically significantly worse with protocol A. There were no differences in
      enhancement or noise score of the liver. Tumor delineation and pleural findings
      were better evaluated with delayed phase images. Dose-length product was
      significantly higher with protocol A (645.0 vs 521.5 mGy . cm; p < 0.0001).
      CONCLUSION: A single 60-second delayed acquisition for thoracic and abdominal
      contrast-enhanced CT is associated with less contrast artifact and affords better
      visualization of lymph nodes at a lower radiation dose while acceptable vascular
      and hepatic contrast enhancement is maintained.

PMID- 29570377
TI  - Pheochromocytomas Versus Adenoma: Role of Venous Phase CT Enhancement.
AB  - OBJECTIVE: Our objective was to investigate whether the quantitative measurement
      of venous phase enhancement on CT can distinguish a pheochromocytoma from an
      adrenal adenoma. MATERIALS AND METHODS: A pathology database was retrospectively
      appraised over a period of 7 years and revealed 43 histopathologically proven
      adrenal adenomas and 34 pheochromocytomas. The lesion densities were measured on
      the 60-second venous phase CT on all adrenal lesions to assess venous phase
      enhancement values. RESULTS: Venous phase enhancement of 85 HU or greater
      afforded a sensitivity, specificity, positive predictive value, and negative
      predictive value of 88.2%, 83.7%, 81.1%, and 90%, respectively (p < 0.0001). The
      positive likelihood ratio was 5.42. Venous phase enhancement of >= 85 HU was
      detected in 30 (88.2%) pheochromocytomas (p < 0.001) and in seven (16.3%)
      adenomas. Venous phase enhancement of < 85 HU was detected in four (11.8%)
      pheochromocytomas and in 36 (83.7%) adenomas. Of the pheochromocytomas imaged
      with a triphasic protocol (n = 15), 66.7% (n = 10) met both absolute and relative
      percentage washout criteria for the diagnosis of a lipid-poor adenoma (p > 0.1).
      CONCLUSION: A significant subset of pheochromocytomas mimics adenomas on absolute
      or relative percentage washout calculations. However, nodules with venous phase
      enhancement of 85 HU or more are much more likely to be pheochromocytomas than
      adenomas, regardless of whether the lesion shows absolute or relative percentage
      washout compatible with a lipid-poor adenoma. The typical values of absolute and
      relative percentage washout of adrenal adenoma should be interpreted along with
      the venous phase enhancement value to avoid potential misdiagnoses.

PMID- 29570378
TI  - JOURNAL CLUB: Preparative Fasting for Contrast-Enhanced CT in a Cancer Center: A
      New Approach.
AB  - OBJECTIVE: Most diagnostic imaging centers ask patients to fast for 4-6 hours
      before contrast-enhanced CT. Previous studies have shown that prolonged fasting
      can be harmful. In addition, manufacturers of contrast agents claim that there is
      no special preparation needed before examination. The aim of this study was to
      evaluate the effects of preparative fasting on contrast-enhanced CT at a cancer
      center. SUBJECTS AND METHODS: Outpatients (n = 3206) were prospectively evaluated
      and randomly assigned to two groups: the 1619 patients in group 1 fasted for at
      least 4 hours before the examination, whereas the 1587 patients in group 2
      received a light meal. Adverse symptoms observed before and after contrast agent
      administration were compared between groups. RESULTS: Adverse symptoms occurring
      after IV contrast agent administration were reported by 45 patients (1.5%) in
      group 1 and 30 patients (0.9%) in group 2. The most common symptoms were nausea
      (n = 32), weakness (n = 12), and vomiting (n = 5). The frequency of symptoms did
      not differ statistically significantly between groups (p > 0.05). CONCLUSION: In
      this sample of patients with cancer undergoing contrast-enhanced CT, very few
      adverse symptoms were reported regardless of preparative fasting. These results
      support the idea that preparation for contrast-enhanced CT can be simplified,
      decreasing the discomfort and inconvenience experienced by patients.

PMID- 29570379
TI  - 2013-2018: New and Ongoing Challenges.

PMID- 29570380
TI  - Neonatal Macroglossia: Demographics, Cost of Care, and Associated Comorbidities.
AB  - OBJECTIVES: To examine the birth prevalence of congenital macroglossia and
      identify demographic variables and comorbidities that may influence length of
      stay and cost of care. STUDY DESIGN: Retrospective cross-sectional study using
      the Kids' Inpatient Database 2003, 2006, 2009, and 2012. METHODS: Demographics
      were analyzed. Linear regression modeling and multivariate analyses were
      performed. RESULTS: The birth prevalence of congenital macroglossia was 4.63/100
      000 births. Patients were classified as isolated (n = 349, 48.1%) or syndromic (n
      = 377, 51.9%). A higher incidence of isolated macroglossia was seen in females
      (odds ratio, OR [95% confidence interval, 95% CI]: 1.93 [1.45-2.56] and African
      Americans (2.02 [1.41-2.88]). Length of stay was higher for syndromic patients
      than for nonsyndromic patients (22.6 days [18.6-26.6] vs 7.93 days [5.95-9.90],
      as were inpatient costs ($3619USD [$27 628-$44 754] vs $10 168USD [$6272-$14
      064]. After accounting for gender, race, location, and socioeconomic status, the
      presence of macroglossia alone increased length of stay by 4.07 days (0.42-7.72
      days) in nonsyndromic patients and 12.02 days (3.63-20.4 days) in syndromic
      patients. The cost of care increased by $6207USD ($576-$11 838) among
      nonsyndromic newborns and $17 205USD ($374-34 035) among syndromic patients.
      CONCLUSION: The birth prevalence of congenital isolated macroglossia appears to
      vary by sex and race. Prolonged length of stay and increased costs are associated
      with both isolated macroglossia and syndromic macroglossia, even after
      controlling for other syndromic comorbidities.

PMID- 29570381
TI  - Sociodemographic Predictors of Missed Appointments Among Patients With Cleft Lip
      and Palate.
AB  - OBJECTIVE: To identify disparities in compliance of and care for patients with
      cleft lip and/or palate (CL/P) by determining the impact of sociodemographic
      variables on the rate of missed appointments and Child Protective Services (CPS)
      involvement. DESIGN: A retrospective, noninterventional quality assessment and
      quality improvement study were designed. SETTING: This institutional study was
      performed at the University of Michigan in Ann Arbor, Michigan. PATIENTS: All
      patients born between January 1, 2011, and December 31, 2014, who underwent
      surgical CL/P repair, excluding those with fewer than 5 appointments (n = 178).
      MAIN OUTCOME MEASURE: The rate of missed appointments, calculated as the total
      number of no-show appointments divided by the total number of scheduled
      appointments. All appointments from CL/P diagnosis to data collection were
      considered, including those outside of plastic surgery. RESULTS: The average
      patient was 4.5 years of age and had 49 total scheduled appointments. The overall
      rate of missed appointments was 9.6%, with 66.8% of patients missing at least 1
      scheduled visit. Patients who were black ( P = .04), not affiliated with a
      religion ( P = .01), Medicaid users ( P = .01), from an unstable social
      background ( P = .01), or received need-based financial assistance ( P = .00)
      were significantly more likely to miss appointments. Child Protective Services
      was involved with 3.9% of patients. CONCLUSIONS: Disparities exist in attendance
      rates among patients with CL/P, and at-risk patient populations have been
      identified. The allocation of cleft care resources must be efficiently planned in
      order to enhance the quality of care for at-risk individuals.

PMID- 29570382
TI  - #CleftProud: A Content Analysis and Online Survey of 2 Cleft Lip and Palate
      Facebook Groups.
AB  - BACKGROUND: More than 2 billion people worldwide now use social networking sites,
      with an increasing number of users accessing these sites to obtain health
      information and engage in emotional support. Yet, investigation of social
      networking sites in the context of cleft lip and/or palate (CL/P) has been
      scarce. METHODS: Real-time data posted during 2 weeks in April 2017 were
      collected from 2 existing private Facebook groups (hosted by the Cleft Lip and
      Palate Association United Kingdom) using video screen capture software. The
      number of posts, comments, unique contributors, and post "likes" was recorded, as
      well as the type and theme of each post. Data relating to the benefits and
      challenges of participation in the 2 groups were also collected via an online
      survey. RESULTS: A content analysis of real-time data identified perioperative
      care, associated syndromes, and dental health to be particular areas of concern
      for parents/caregivers. Expectations, experiences, and outcomes of further
      treatment were key topics of discussion for adults with CL/P. Common benefits of
      the groups included the ability to connect with others, learn about local events,
      give and receive emotional support, and obtain quick responses to queries in a
      semi-anonymous environment. Disadvantages of the groups included a reliance upon
      opinion rather than medical fact and the frequent use of inappropriate
      terminology. CONCLUSIONS: Social networking sites appear to be a helpful source
      of health-related information and peer support for the CL/P population, yet
      closer monitoring of these groups may be required.

PMID- 29570383
TI  - Segmental Maxillary Distraction Osteogenesis With a Hybrid-Type Distractor in the
      Management of Wide Alveolar Cleft.
AB  - OBJECTIVE: To investigate segmental maxillary distraction osteogenesis (DO) with
      hybrid-type distractor in the management of wide alveolar cleft. PATIENTS AND
      METHODS: Six patients underwent segmental DO with a hybrid-type distractor. After
      the success of DO and 3-month consolidation period, removal of the distractor was
      accompanied by alveolar bone graft with iliac bone. Panoramic radiograph and
      computed tomography scanning were taken preoperatively (T0) and the day after
      distractor removal (T1). The crest distance between the long axis of cleft nearby
      teeth was measured. RESULT: All patients completed the DO period, and the
      succeeding alveolar bone graft healing was uneventful. The mean cleft distance
      decrease was 12.05 mm (range: 10.1-13.5 mm). As for the mobility degree record of
      abutment tooth in the transport segment recorded, 6 patients were grading I
      degrees  at T0, while 5 patients were grading I degrees  and 1 patient was
      grading II degrees  at T1. CONCLUSION: Segmental maxillary DO with the hybrid
      type distractor is successful to reduce the cleft width in these cases, and it is
      promising in the treatment of wide dental alveolar cleft, especially for the
      adult patient.

PMID- 29570384
TI  - The Effects of Age at Cleft Palate Repair on Middle Ear Function and Hearing
      Level.
AB  - OBJECTIVE: To investigate the age effects of cleft palate repair on middle ear
      function and hearing level in patients who underwent cleft palate repair at
      different ages by audiologic examination. METHODS: Medical histories were
      gathered in detail, and audiologic tests (ie, tympanometry and pure tone hearing
      threshold) were conducted in 126 patients after palatoplasty. The patients were
      divided into the following 4 groups according to their ages when they underwent
      cleft palate repair: group I (0-3 years, 73 patients), group II (4-7 years, 29
      patients), group III (8-11 years, 16 patients), and group IV (12 years and older,
      8 patients). The data regarding tympanograms, hearing levels, and the average
      hearing thresholds of each group were analyzed using chi-square tests. RESULTS:
      The prevalence of middle ear dysfunction and hearing loss in the patients who
      underwent palatoplasty before 3 years old (27.4% and 2.0% respectively) was
      significantly lower than that in patients who underwent palatopalsty at 12 years
      or older (75.0% and 43.7%, respectively). Linear-by-linear association revealed
      that the prevalences of middle ear dysfunction and hearing loss among the 4
      groups were significantly different ( P < .05). CONCLUSIONS: The prevalence of
      middle ear dysfunction and hearing loss tended to increase with advancing age at
      the time of cleft palate repair. From an audiologist's perspective, palatoplasty
      at an early age is very beneficial in helping children with cleft palates acquire
      better middle ear function and hearing level.

PMID- 29570385
TI  - Stereotactic laser ablation of amygdala and hippocampus using a Leksell
      stereotactic frame.
AB  - Approximately one-third of patients with epilepsy are resistant to medical
      therapy, particularly in those with mesial temporal lobe epilepsy. While there
      are several surgical modalities, efforts have been focused on developing safer
      and minimally invasive techniques. In this video, the authors present the case of
      a 45-year-old woman with a 2-year history of refractory left mesial temporal lobe
      epilepsy who underwent MRI-guided laser ablation of amygdala and hippocampus.
      There were no perioperative complications. The video can be found here:
      https://youtu.be/XFHt2jTdE_4 .

PMID- 29570386
TI  - Laser interstitial thermal therapy for an eloquent region supratentorial brain
      lesion.
AB  - Laser interstitial thermal therapy (LITT) is a minimally invasive stereotactic
      technique that causes tumor ablation using thermal energy. LITT has shown to be
      efficacious for the treatment of deep-seated brain lesions, including those near
      eloquent areas. In this video, the authors present the case of a 62-year-old man
      with a history of metastatic melanoma who presented with worsening right-sided
      hemiparesis. MRI revealed a contrast-enhancing lesion in left centrum semiovale
      in close proximity to corticospinal tracts, consistent with radiation necrosis.
      The authors review their stepwise technique of LITT with special attention to
      details for a lesion located near eloquent area. The video can be found here:
      https://youtu.be/ndrTgi6MXqE .

PMID- 29570387
TI  - Introduction to Laser Ablation Video Supplement.
AB  - Laser ablation (also known as laser interstitial thermal therapy [LITT]) has
      emerged as an important new technology for treating various disorders of the
      brain and spine. As with any new or emerging technology, there is a learning
      curve for its optimal use, and video tutorials can be important learning tools to
      help bridge gaps in knowledge for those who wish to become more familiar with
      laser ablation. In this special supplement to Neurosurgical Focus, videos
      illustrate laser ablation's use in the treatment of epilepsy and failed
      radiosurgery, as well as technical aspects of performing these procedures in
      eloquent brain and in the spine. We hope that these videos will enable you to
      enhance your understanding of the evolving use of laser ablation for disorders of
      the brain or spine. It is the editors' sincere hope that this will be helpful
      either in your own practice or in determining whether to refer to a neurosurgical
      colleague experienced in this field.

PMID- 29570388
TI  - Contemporaneous biopsy and laser interstitial thermal therapy for two treatment
      refractory brain metastases.
AB  - Recurrent treatment-refractory brain metastases can be treated with modern
      adjuvant therapies such as laser interstitial thermal therapy (LITT). Since
      previously radiated lesions may be indolent (treatment effect) or recurrent
      tumor, histological confirmation may be helpful. The authors present the utility
      of contemporaneous biopsy and LITT using intraoperative O-arm navigation in a
      patient who presented with multiple refractory metastases. The authors
      demonstrate the utility of O-arm navigation to confirm intraoperative biopsy and
      LITT placement. Concurrent stereotactic biopsy and LITT may be a safe and
      efficacious method for both the diagnosis and treatment of deep lesions that are
      unamenable to standard adjuvant treatment modalities. The video can be found
      here: https://youtu.be/SUY-qiahMyo .

PMID- 29570389
TI  - Anterior two-thirds corpus callosotomy via stereotactic laser ablation.
AB  - Anterior two-thirds corpus callosotomy is a common palliative surgical
      intervention most commonly employed in patients with atonic or drop seizures.
      Recently, stereotactic laser ablation of the corpus callosum without a craniotomy
      has shown promise in achieving similar outcomes with fewer side effects and
      shorter hospitalizations. The authors demonstrate ablation of the anterior two
      thirds corpus callosum in a patient with Lennox-Gastaut syndrome and drug
      resistant drop seizures. Technical nuances of laser ablation with 3 laser fibers
      are described. Postoperatively, the patient showed a significant reduction in
      seizure frequency and severity over a 9-month follow-up period. The video can be
      found here: https://youtu.be/3-mMq5-PLiM .

PMID- 29570390
TI  - Laser interstitial thermal therapy of the spine: technical aspects.
AB  - Spinal laser interstitial thermal therapy has been developed as a minimally
      invasive modality to treat epidural spinal tumors percutaneously. The safe and
      effective use of this technology requires meticulous preoperative trajectory
      planning and an intraoperative workflow incorporating navigation and MR
      thermography. Instrumented stabilization can be performed during the same
      operation if needed. Operative considerations and technical aspects are reviewed.
      The video can be found here: https://youtu.be/P--frsag6gU .

PMID- 29570391
TI  - Deletion of choline acetyltransferase in enteric neurons results in postnatal
      intestinal dysmotility and dysbiosis.
AB  - Acetylcholine (ACh)-synthesizing neurons are major components of the enteric
      nervous system (ENS). They release ACh and peptidergic neurotransmitters onto
      enteric neurons and muscle. However, pharmacological interrogation has proven
      inadequate to demonstrate an essential role for ACh. Our objective was to
      determine whether elimination of ACh synthesis during embryogenesis alters
      prenatal viability, intestinal function, the neurotransmitter complement, and the
      microbiome. Conditional deletion of choline acetyltransferase ( ChAT), the ACh
      synthetic enzyme, in neural crest-derived neurons ( ChAT-Null) was performed.
      Survival, ChAT activity, gut motility, and the microbiome were studied. ChAT was
      conditionally deleted in ENS neural crest-derived cells. Despite ChAT absence,
      mice were born live and survived the first 2 wk. They failed to gain significant
      weight in the third postnatal week, dying between postnatal d 18 and 30. Small
      intestinal transit of carmine red was 50% slower in ChAT-Nulls vs. WT and ChAT-
      Het. The colons of many neonatal ChAT-Null mice contained compacted feces,
      suggesting dysmotility. Microbiome analysis revealed dysbiosis in ChAT-Null mice.
      Developmental deletion of ChAT activity in enteric neurons results in proximal
      gastrointestinal tract dysmotility, critically diminished colonic transit,
      failure to thrive, intestinal dysbiosis, and death. ACh is necessary for
      sustained gut motility and survival of neonatal mice after weaning.-Johnson, C.
      D., Barlow-Anacker, A. J., Pierre, J. F., Touw, K., Erickson, C. S., Furness, J.
      B., Epstein, M. L., Gosain, A. Deletion of choline acetyltransferase in enteric
      neurons results in postnatal intestinal dysmotility and dysbiosis.

PMID- 29570393
TI  - A new role for HERPUD1 and ERAD activation in osteoblast differentiation and
      mineralization.
AB  - Bone integrity depends on a finely tuned balance between bone synthesis by
      osteoblasts and resorption by osteoclasts. The secretion capacity of mature
      osteoblasts requires strict control of proteostasis. Endoplasmic reticulum
      associated degradation (ERAD) prevents the accumulation of unfolded ER proteins
      via dislocation to the cytosol and degradation by the proteasome. The ER membrane
      protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like
      domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which
      helps to stabilize the complex and facilitate the efficient degradation of
      unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded
      protein response and cellular stress. The aim of the current study was to
      establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and
      maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast
      differentiation by measuring calcium deposit levels, alkaline phosphatase
      activity, and runt-related transcription factor 2 and osterix expression. We
      found that ERAD and proteasomal degradation were activated and that HERPUD1
      expression was increased as osteoblast differentiation progressed. The absence of
      HERPUD1 blocked osteoblast mineralization in vitro and significantly reduced
      alkaline phosphatase activity. In contrast, HERPUD1 overexpression activated the
      osteoblast differentiation program. Our results demonstrate that HERPUD1 and ERAD
      are important for the activation of the osteoblast maturation program and may be
      useful new targets for elucidating bone physiology.-Americo-Da-Silva, L., Diaz,
      J., Bustamante, M., Mancilla, G., Oyarzun, I., Verdejo, H. E., Quiroga, C. A new
      role for HERPUD1 and ERAD activation in osteoblast differentiation and
      mineralization.

PMID- 29570392
TI  - Neonatal mouse intervertebral discs heal with restored function following
      herniation injury.
AB  - Adult intervertebral discs (IVDs) have poor endogenous healing capacity, because
      of their challenging microenvironment and complex mechanical demands, which can
      result in painful IVD herniation. There are no regenerative strategies available
      to improve IVD healing and restore its function. Neonatal mice are excellent
      models of mammalian regeneration, but there are no studies of the regenerative
      capacity of neonatal IVDs. In this study, we developed a neonatal model of
      improved IVD healing to inform repair strategies after herniation. In vivo
      puncture injuries were performed to simulate herniation with complete annulus
      fibrosus (AF) tears in caudal IVDs of neonatal (postnatal d 5) and adult (4-6 mo)
      Scleraxis green fluorescent protein ( ScxGFP) mice. Acute and long-term healing
      responses were assessed with histologic, radiologic, and biomechanical
      measurements. Neonates underwent accelerated IVD healing compared to adults with
      functional restoration and enhanced structural repair after herniation. A
      population of ScxGFP- cells identified in the neonatal repair site may be
      associated with this improved healing and warrants future investigation. In
      summary, function of neonatal IVDs was restored after herniation injury, whereas
      that of adult discs was not. This improved healing response is likely driven by
      multiple mechanisms that may include differences in mechanical loading and
      available repair cells during growth.-Torre, O. M., Das, R., Berenblum, R. E.,
      Huang, A. H., Iatridis, J. C. Neonatal mouse intervertebral discs heal with
      restored function following herniation injury.

PMID- 29570394
TI  - Maternal and umbilical cord serum-derived exosomes enhance endothelial cell
      proliferation and migration.
AB  - We investigated the role of exosomes derived from maternal and umbilical cord
      blood in the regulation of angiogenesis. We report here that both maternal
      exosomes (MEs) and umbilical exosomes (UEs) significantly enhance HUVEC
      proliferation, migration, and tube formation. Importantly, ME-treated HUVECs
      (MEXs) displayed significantly increased migration, but not proliferation or tube
      formation, compared with UE-treated HUVECs (UEXs). We found that the expression
      of a subset of migration-related microRNAs (miRNAs), including miR-210-3p, miR
      376c-3p, miR-151a-5p, miR-296-5p, miR-122-5p, and miR-550a-5p, among others, were
      significantly increased or decreased in UEs, and this altered expression was
      likely correlated with the differential regulation of HUVEC migration. We also
      found that the mRNA expression of hepatocyte growth factor (HGF) was up-regulated
      in MEXs and UEXs and, moreover, that inhibiting HGF partially abolished the
      enhanced cell migration induced by UEs. Our results suggest that both MEs and UEs
      greatly enhanced endothelial cell (EC) functions and differentially regulated EC
      migration, which was mostly attributed to the different expression profiles of
      exosomal miRNA. These findings highlight the importance of exosomes in the
      regulation of angiogenesis during pregnancy. Exosomal miRNAs, in particular, may
      be of great significance for the regulation of angiogenesis in maintaining normal
      pregnancy.-Jia, L., Zhou, X., Huang, X., Xu, X., Jia, Y., Wu, Y., Yao, J., Wu,
      Y., Wang, K. Maternal and umbilical cord serum-derived exosomes enhance
      endothelial cell proliferation and migration.

PMID- 29570396
TI  - Carbon-14 bomb pulse dating shows that tendinopathy is preceded by years of
      abnormally high collagen turnover.
AB  - Tendons are essential weight-bearing structures that are often affected by
      tendinopathy, which leads to pain and impaired mobility. In healthy Achilles
      tendons, no significant renewal of the weight-bearing collagen matrix seems to
      occur during adult life, but tendinopathy may lead to increased turnover. The
      carbon-14 ([14C]) bomb pulse method was used to measure lifelong replacement
      rates of collagen in tendinopathic and healthy Achilles tendons (tendinopathic: n
      = 25, born 1937-1972. Healthy: n = 10, born 1929-1966). As expected, the healthy
      tendon collagen had not been replaced during adulthood, but in tendinopathic
      tendon, a substantial renewal had occurred. Modeling of the [14C] data suggested
      that one half of the collagen in tendinopathic matrix had undergone continuous
      slow turnover for years before the presentation of symptoms. This finding allows
      for a new concept in tendon pathogenesis because it suggests that either the
      symptoms of tendinopathy represent a late phase of a very prolonged disease
      process, or an abnormally high collagen exchange could be a risk factor for
      tendon disorders rather than being a result of disease.-Heinemeier, K. M.,
      Schjerling, P., Ohlenschlaeger, T. F., Eismark, C., Olsen, J., Kjaer, M. Carbon
      14 bomb pulse dating shows that tendinopathy is preceded by years of abnormally
      high collagen turnover.

PMID- 29570395
TI  - Eliciting unnatural immune responses by activating cryptic epitopes in viral
      antigens.
AB  - Antigenic variation in viral surface antigens is a strategy for escaping the
      host's adaptive immunity, whereas regions with pivotal functions for infection
      are less subject to antigenic variability. We hypothesized that genetically
      invariable and immunologically dormant regions of a viral surface antigen could
      be exposed to the host immune system and activated by rendering them susceptible
      to antigen-processing machinery in professional antigen-presenting cells (APCs).
      Considering the frequent antigen drift and shift in influenza viruses, we
      identified and used structural modeling to evaluate the conserved regions on the
      influenza hemagglutinin (HA) surface as potential epitopes. Mutant viruses
      containing the cleavage motifs of cathepsin S within HA were generated.
      Immunization of mice showed that the mutant, but not the wild-type virus,
      elicited specific antibodies against the cryptic epitope. Those antibodies were
      purified, and specific binding to HA was confirmed. These results suggest that an
      unnatural immune response can be elicited through the processing of target
      antigens in APCs, followed by presentation via the major histocompatibility
      complex, if not subjected to regulatory pathways. By harnessing the antigen
      processing machinery, our study shows a proof-of-principle for designer vaccines
      with increased efficacy and safety by either activating cryptic, or inactivating
      naturally occurring, epitopes of viral antigens.-Lee, Y. J., Yu, J. E., Kim, P.,
      Lee, J.-Y., Cheong, Y. C., Lee, Y. J., Chang, J., Seong, B. L. Eliciting
      unnatural immune responses by activating cryptic epitopes in viral antigens.

PMID- 29570398
TI  - Constraints Imposed by a Natural Landscape Override Offspring Fitness Effects to
      Shape Oviposition Decisions in Wild Forked Fungus Beetles.
AB  - Oviposition site decisions often maximize offspring fitness, but costs
      constraining choice can cause females to oviposit in poor developmental
      environments. It is unclear whether these constraints cumulatively outweigh
      offspring fitness to determine oviposition decisions in wild populations.
      Understanding how constraints shape oviposition in natural landscapes is a
      critical step toward revealing how maternal behavior influences fundamental
      phenomena like the evolution of specialization and the use of sink environments.
      Here, we used a genetic capture-recapture technique to reconstruct the
      oviposition decisions of individual females in a natural metapopulation of a
      beetle (Bolitotherus cornutus) that oviposits on three fungus species. We
      measured larval fitness-related traits (mass, development time, survival) on each
      fungus and compared the oviposition preferences of females in laboratory versus
      field tests. Larval fitness differed substantially among fungi, and females
      preferred a high-quality (high larval fitness) fungus in laboratory trials.
      However, females frequently laid eggs on the lowest-quality fungus in the wild.
      They preferred high-quality fungi when moving between oviposition sites, but this
      preference disappeared as the distance between sites increased and was
      inconsistent between study plots. Our results suggest that constraints on
      oviposition preferences in natural landscapes are sufficiently large to drive
      oviposition in poor developmental environments even when offspring fitness
      consequences are severe.

PMID- 29570397
TI  - The tumor secretory factor ZAG promotes white adipose tissue browning and energy
      wasting.
AB  - Cachexia is a complex tissue-wasting syndrome characterized by inflammation,
      hypermetabolism, increased energy expenditure, and anorexia. Browning of white
      adipose tissue (WAT) is one of the significant factors that contribute to energy
      wasting in cachexia. By utilizing a cell implantation model, we demonstrate here
      that the lipid mobilizing factor zinc-alpha2-glycoprotein (ZAG) induces WAT
      browning in mice. Increased circulating levels of ZAG not only induced lipolysis
      in adipose tissues but also caused robust browning in WAT. Stimulating WAT
      progenitors with ZAG recombinant protein or expression of ZAG in mouse embryonic
      fibroblasts (MEFs) strongly enhanced brown-like differentiation. At the molecular
      level, ZAG stimulated peroxisome proliferator-activated receptor gamma
      (PPARgamma) and early B cell factor 2 expression and promoted their recruitment
      to the PR/SET domain 16 (Prdm16) promoter, leading to enhanced expression of
      Prdm16, which determines brown cell fate. In brown adipose tissue, ZAG stimulated
      the expression of PPARgamma and PPARgamma coactivator 1alpha and promoted
      recruitment of PPARgamma to the uncoupling protein 1 (Ucp1) promoter, leading to
      increased expression of Ucp1. Overall, our results reveal a novel function of ZAG
      in WAT browning and highlight the targeting of ZAG as a potential therapeutic
      application in humans with cachexia.-Elattar, S., Dimri, M., Satyanarayana, A.
      The tumor secretory factor ZAG promotes white adipose tissue browning and energy
      wasting.

PMID- 29570399
TI  - Temperature Drives Epidemics in a Zooplankton-Fungus Disease System: A Trait
      Driven Approach Points to Transmission via Host Foraging.
AB  - Climatic warming will likely have idiosyncratic impacts on infectious diseases,
      causing some to increase while others decrease or shift geographically. A
      mechanistic framework could better predict these different temperature-disease
      outcomes. However, such a framework remains challenging to develop, due to the
      nonlinear and (sometimes) opposing thermal responses of different host and
      parasite traits and due to the difficulty of validating model predictions with
      observations and experiments. We address these challenges in a zooplankton-fungus
      (Daphnia dentifera-Metschnikowia bicuspidata) system. We test the hypothesis that
      warmer temperatures promote disease spread and produce larger epidemics. In
      lakes, epidemics that start earlier and warmer in autumn grow much larger. In a
      mesocosm experiment, warmer temperatures produced larger epidemics. A mechanistic
      model parameterized with trait assays revealed that this pattern arose primarily
      from the temperature dependence of transmission rate (beta), governed by the
      increasing foraging (and, hence, parasite exposure) rate of hosts (f). In the
      trait assays, parasite production seemed sufficiently responsive to shape
      epidemics as well; however, this trait proved too thermally insensitive in the
      mesocosm experiment and lake survey to matter much. Thus, in warmer environments,
      increased foraging of hosts raised transmission rate, yielding bigger epidemics
      through a potentially general, exposure-based mechanism for ectotherms. This
      mechanistic approach highlights how a trait-based framework will enhance
      predictive insight into responses of infectious disease to a warmer world.

PMID- 29570400
TI  - Inferring Causalities in Landscape Genetics: An Extension of Wright's Causal
      Modeling to Distance Matrices.
AB  - Identifying landscape features that affect functional connectivity among
      populations is a major challenge in fundamental and applied sciences. Landscape
      genetics combines landscape and genetic data to address this issue, with the main
      objective of disentangling direct and indirect relationships among an intricate
      set of variables. Causal modeling has strong potential to address the complex
      nature of landscape genetic data sets. However, this statistical approach was not
      initially developed to address the pairwise distance matrices commonly used in
      landscape genetics. Here, we aimed to extend the applicability of two causal
      modeling methods-that is, maximum-likelihood path analysis and the directional
      separation test-by developing statistical approaches aimed at handling distance
      matrices and improving functional connectivity inference. Using simulations, we
      showed that these approaches greatly improved the robustness of the absolute
      (using a frequentist approach) and relative (using an information-theoretic
      approach) fits of the tested models. We used an empirical data set combining
      genetic information on a freshwater fish species (Gobio occitaniae) and detailed
      landscape descriptors to demonstrate the usefulness of causal modeling to
      identify functional connectivity in wild populations. Specifically, we
      demonstrated how direct and indirect relationships involving altitude,
      temperature, and oxygen concentration influenced within- and between-population
      genetic diversity of G. occitaniae.

PMID- 29570401
TI  - Calculating Competitive Intransitivity: Computational Challenges.
AB  - Intransitive (or "rock-paper-scissors") competition is compelling because it
      promotes species coexistence and because recent work suggests that it may be
      common in natural systems. One class of intransitivity indices works by
      considering s, the minimum number of competitive reversals to convert a given
      competitive community (i.e., a "tournament") to a hierarchy. The most
      straightforward example of such "reversal-based" indices is Petraitis's index,
      [Formula: see text], where M is the maximum s across all possible n-species
      tournaments. Using exhaustive searches, we prove that Petraitis's formula for M
      (and, therefore, t) does not hold for [Formula: see text]. Furthermore,
      determination of s for even moderate values of n may prove difficult, as the
      equivalent graph theoretical problem is NP (nondeterministic polynomial time)
      hard; there is no known computationally feasible way to compute an exact answer
      for anything but small values of n, let alone a closed-form solution. Petraitis's
      t is a valuable index of intransitivity; however, at present its use is limited
      to relatively species-poor systems. More broadly, reversal-based indices, while
      intuitive, may be problematic because of this computability issue.

PMID- 29570402
TI  - Evolution of Genetic Variance during Adaptive Radiation.
AB  - Genetic correlations between traits can concentrate genetic variance into fewer
      phenotypic dimensions that can bias evolutionary trajectories along the axis of
      greatest genetic variance and away from optimal phenotypes, constraining the rate
      of evolution. If genetic correlations limit adaptation, rapid adaptive divergence
      between multiple contrasting environments may be difficult. However, if natural
      selection increases the frequency of rare alleles after colonization of new
      environments, an increase in genetic variance in the direction of selection can
      accelerate adaptive divergence. Here, we explored adaptive divergence of an
      Australian native wildflower by examining the alignment between divergence in
      phenotype mean and divergence in genetic variance among four contrasting
      ecotypes. We found divergence in mean multivariate phenotype along two major axes
      represented by different combinations of plant architecture and leaf traits.
      Ecotypes also showed divergence in the level of genetic variance in individual
      traits and the multivariate distribution of genetic variance among traits.
      Divergence in multivariate phenotypic mean aligned with divergence in genetic
      variance, with much of the divergence in phenotype among ecotypes associated with
      changes in trait combinations containing substantial levels of genetic variance.
      Overall, our results suggest that natural selection can alter the distribution of
      genetic variance underlying phenotypic traits, increasing the amount of genetic
      variance in the direction of natural selection and potentially facilitating rapid
      adaptive divergence during an adaptive radiation.

PMID- 29570404
TI  - Neglected Patterns of Variation in Phenotypic Plasticity: Age- and Sex-Specific
      Antipredator Plasticity in a Cichlid Fish.
AB  - The ability of organisms to plastically respond to changing environments is well
      studied. However, variation in phenotypic plasticity during ontogeny is less well
      understood despite its relevance of being an important source of phenotypic
      variation in nature. Here, we comprehensively study ontogenetic variation in
      morphological antipredator plasticity across multiple traits in Pelvicachromis
      taeniatus, a western African cichlid fish with sexually dimorphic ornamentation.
      In a split-clutch design, fish were raised under different levels of perceived
      predation risk (conspecific alarm cues or distilled water). Morphological
      plasticity varied substantially across ontogeny: it was first observable at an
      early juvenile stage where alarm cue-exposed fish grew faster. Subsequently,
      significant plasticity was absent until the onset of sexual maturity. Here, alarm
      cue-exposed males were larger than control males, which led to deeper bodies,
      longer dorsal spines, larger caudal peduncles, and increased eye diameters.
      Sexual ornamentation emerged delayed in alarm cue-exposed males. In later
      adulthood, the plastic responses receded. Despite small effect sizes, these
      responses represent putative adaptive plasticity, as they are likely to reduce
      predation risk. In females, we did not observe any plasticity. In accordance with
      theory, these results suggest fine-tuned expression of plasticity that
      potentially increases defenses during vulnerable developmental stages and
      reproductive output.

PMID- 29570403
TI  - Venus Flytrap Rarely Traps Its Pollinators.
AB  - Because carnivorous plants rely on arthropods as pollinators and prey, they risk
      consuming would-be mutualists. We examined this potential conflict in the Venus
      flytrap (Dionaea muscipula), whose pollinators were previously unknown. Diverse
      arthropods from two classes and nine orders visited flowers; 56% of visitors
      carried D. muscipula pollen, often mixed with pollen of coflowering species.
      Within this diverse, generalized community, certain bee and beetle species appear
      to be the most important pollinators, on the basis of their abundance, pollen
      load size, and pollen fidelity. Dionaea muscipula prey spanned four invertebrate
      classes and 11 orders; spiders, beetles, and ants were most common. At the family
      and species levels, few taxa were shared between traps and flowers, yielding a
      near-zero value of niche overlap for these potentially competing structures.
      Spatial separation of traps and flowers may contribute to partitioning the
      invertebrate community between nutritional and reproductive functions in D.
      muscipula.

PMID- 29570405
TI  - Model Adequacy and Microevolutionary Explanations for Stasis in the Fossil
      Record.
AB  - Long-term phenotypic stasis is frequently observed in the fossil record, but not
      readily predicted from microevolutionary theory. To test competing explanations
      for stasis on macroevolutionary timescales we need reliably estimated parameters
      from appropriate evolutionary models that adequately describe the evolutionary
      trait dynamics. Here, we develop tests to assess the adequacy of the most
      commonly used stasis model in evolutionary biology and apply them to time series
      of phenotypic traits from fossil lineages. Of the 572 fossil time series we
      analyzed from the literature, 263 time series showed a better fit to the stasis
      model relative to alternative models, but only 172 of those fitted the stasis
      model in both relative and absolute terms. The estimated trait variances from
      these 172 time series do not correlate with rough proxies of effective population
      size. Our preliminary investigation of the fixed-optimum hypothesis hence fails
      to give empirical support to the idea that genetic drift around a constant trait
      optimum is an explanation for stasis in the fossil record. We argue that optima
      following stationary processes on the adaptive landscape is a viable hypothesis
      for stasis that needs further investigation. We end by discussing how
      investigations of model adequacy can be a valuable approach for increasing our
      understanding of the dynamics of the adaptive landscape on macroevolutionary
      timescales.

PMID- 29570406
TI  - Neutral Community Dynamics and the Evolution of Species Interactions.
AB  - A contemporary goal in ecology is to determine the ecological and evolutionary
      processes that generate recurring structural patterns in mutualistic networks.
      One of the great challenges is testing the capacity of neutral processes to
      replicate observed patterns in ecological networks, since the original
      formulation of the neutral theory lacks trophic interactions. Here, we develop a
      stochastic-simulation neutral model adding trophic interactions to the neutral
      theory of biodiversity. Without invoking ecological differences among individuals
      of different species, and assuming that ecological interactions emerge randomly,
      we demonstrate that a spatially explicit multitrophic neutral model is able to
      capture the recurrent structural patterns of mutualistic networks (i.e., degree
      distribution, connectance, nestedness, and phylogenetic signal of species
      interactions). Nonrandom species distribution, caused by probabilistic events of
      migration and speciation, create nonrandom network patterns. These findings have
      broad implications for the interpretation of niche-based processes as drivers of
      ecological networks, as well as for the integration of network structures with
      demographic stochasticity.

PMID- 29570407
TI  - The Geometry of Nutrient Space-Based Life-History Trade-Offs: Sex-Specific
      Effects of Macronutrient Intake on the Trade-Off between Encapsulation Ability
      and Reproductive Effort in Decorated Crickets.
AB  - Life-history theory assumes that traits compete for limited resources, resulting
      in trade-offs. The most commonly manipulated resource in empirical studies is the
      quantity or quality of diet. Recent studies using the geometric framework for
      nutrition, however, suggest that trade-offs are often regulated by the intake of
      specific nutrients, but a formal approach to identify and quantify the strength
      of such trade-offs is lacking. We posit that trade-offs occur whenever life
      history traits are maximized in different regions of nutrient space, as evidenced
      by nonoverlapping 95% confidence regions of the global maximum for each trait and
      large angles (theta) between linear nutritional vectors and Euclidean distances
      (d) between global maxima. We then examined the effects of protein and
      carbohydrate intake on the trade-off between reproduction and aspects of immune
      function in male and female Gryllodes sigillatus. Female encapsulation ability
      and egg production increased with the intake of both nutrients, whereas male
      encapsulation ability increased with protein intake but calling effort increased
      with carbohydrate intake. The trade-offs between traits was therefore larger in
      males than in females, as demonstrated by significant negative correlations
      between the traits in males, nonoverlapping 95% confidence regions, and larger
      estimates of theta and d. Under dietary choice, the sexes had similar regulated
      intakes, but neither optimally regulated nutrient intake for maximal trait
      expression. We highlight the fact that greater consideration of specific nutrient
      intake is needed when examining nutrient space-based trade-offs.

PMID- 29570408
TI  - Pluck or Luck: Does Trait Variation or Chance Drive Variation in Lifetime
      Reproductive Success?
AB  - While there has been extensive interest in how intraspecific trait variation
      affects ecological processes, outcomes are highly variable even when individuals
      are identical: some are lucky, while others are not. Trait variation is therefore
      important only if it adds substantially to the variability produced by luck. We
      ask when trait variation has a substantial effect on variability in lifetime
      reproductive success (LRS), using two approaches: (1) we partition the variation
      in LRS into contributions from luck and trait variation and (2) we ask what can
      be inferred about an individual's traits and with what certainty, given their
      observed LRS. In theoretical stage- and size-structured models and two empirical
      case studies, we find that luck usually dominates the variance of LRS. Even when
      individuals differ substantially in ways that affect expected LRS, unless the
      effects of luck are substantially reduced (e.g., low variability in reproductive
      life span or annual fecundity), most variance in lifetime outcomes is due to
      luck, implying that departures from "null" models omitting trait variation will
      be hard to detect. Luck also obscures the relationship between realized LRS and
      individual traits. While trait variation may influence the fate of populations,
      luck often governs the lives of individuals.

PMID- 29570409
TI  - Constraining the Time Interval for the Origin of Life on Earth.
AB  - Estimates of the time at which life arose on Earth make use of two types of
      evidence. First, astrophysical and geophysical studies provide a timescale for
      the formation of Earth and the Moon, for large impact events on early Earth, and
      for the cooling of the early magma ocean. From this evidence, we can deduce a
      habitability boundary, which is the earliest point at which Earth became
      habitable. Second, biosignatures in geological samples, including microfossils,
      stromatolites, and chemical isotope ratios, provide evidence for when life was
      actually present. From these observations we can deduce a biosignature boundary,
      which is the earliest point at which there is clear evidence that life existed.
      Studies with molecular phylogenetics and records of the changing level of oxygen
      in the atmosphere give additional information that helps to determine the
      biosignature boundary. Here, we review the data from a wide range of disciplines
      to summarize current information on the timings of these two boundaries. The
      habitability boundary could be as early as 4.5 Ga, the earliest possible estimate
      of the time at which Earth had a stable crust and hydrosphere, or as late as 3.9
      Ga, the end of the period of heavy meteorite bombardment. The lack of consensus
      on whether there was a late heavy meteorite bombardment that was significant
      enough to prevent life is the largest uncertainty in estimating the time of the
      habitability boundary. The biosignature boundary is more closely constrained.
      Evidence from carbon isotope ratios and stromatolite fossils both point to a time
      close to 3.7 Ga. Life must have emerged in the interval between these two
      boundaries. The time taken for life to appear could, therefore, be within 200 Myr
      or as long as 800 Myr. Key Words: Origin of life-Astrobiology-Habitability
      Biosignatures-Geochemistry-Early Earth. Astrobiology 18, 343-364.

PMID- 29570410
TI  - Impact of the Arizona NExSS Winter School on Astrobiology Knowledge and
      Attitudes.
AB  - Astrobiology is an inherently interdisciplinary area of study, demanding
      communication across multiple fields: astronomy, geochemistry, planetary science,
      and so on. Successful communication requires that researchers be aware of the
      basic findings, open questions, and tools and techniques of allied fields and
      possess an appreciation and respect for what these fields consider good science.
      To facilitate this communication between early-career researchers, the Arizona
      NExSS Winter School was hosted in February 2016, bringing together graduate
      students and postdoctoral researchers from backgrounds spanning the field of
      astrobiology. Students virtually attended a scientific Workshop Without Walls and
      participated in lectures, discussions, field trips, and hands-on activities,
      culminating in the writing and review of mock proposals by interdisciplinary
      teams. We assess the impact of the school on interdisciplinarity using a pre- and
      posttest survey of 24 students, informed by National Science Foundation impact
      categories (Friedman et al., 2008 ) within the Impact Analysis Method (IAM)
      described by Davis and Scalice ( 2015 ). We demonstrate that students gained
      knowledge, especially in fields outside their home discipline. Furthermore, an
      underlying disciplinary divide between geochemists and planetary scientists on
      the role of life in planetary evolution is observed and interpreted. These
      findings demonstrate that the Arizona NExSS Winter School had measurable impact
      on interdisciplinarity and that the IAM rubric has utility in measuring impact.
      We make recommendations for further research to understand the interdisciplinary
      gaps in astrobiology and how best to bridge them. Key Words: Interdisciplinarity
      Attitudes-Knowledge-Scientific dialogue-Training. Astrobiology 18, 365-375.

PMID- 29570411
TI  - Manganese Oxides Resembling Microbial Fabrics and Their Implications for
      Recognizing Inorganically Preserved Microfossils.
AB  - In the search for microfossils of early life on Earth, the demonstration of
      biogenicity is paramount. Traditionally, only syngenetic structures with cellular
      elaboration, hollow sheaths/cell walls, and indigenous kerogen have been
      considered bona fide fossils. Recent reports of inorganically preserved
      microfossils represent a shift from this practice. Such a shift, if accompanied
      by a robust set of biogenicity criteria, could have profound implications for the
      identification of biosignatures on early Earth and extraterrestrial bodies. Here,
      we reaffirm the conventional criteria by examining aggregates of inorganic
      filaments from the Pilbara region of Western Australia. These aggregates are
      preserved in bedded chert, and the filaments measure up to 1 MUm in diameter and
      100 MUm in length. The aggregates superficially resemble kerogenous microbial
      fabrics and mycelial organisms. However, the filaments consist of manganese
      oxide, lack cellular elaboration, and show no evidence for hollow sheaths or cell
      walls. We conclude that the filaments are fibrous minerals of abiotic origin. The
      similarities between these pseudofossils and some filamentous fossils highlight
      the need for strict application of the conventional criteria for recognizing
      microfossils. In the absence of kerogen, morphologically simple structures
      should, at least, show evidence of cellular features to be considered bona fide
      fossils. Key Words: Fossil-Manganese oxide-Pilbara-Precambrian-Pseudofossil.
      Astrobiology 18, 249-258.

PMID- 29570412
TI  - Profit-Based Model Selection for Customer Retention Using Individual Customer
      Lifetime Values.
AB  - The goal of customer retention campaigns, by design, is to add value and enhance
      the operational efficiency of businesses. For organizations that strive to retain
      their customers in saturated, and sometimes fast moving, markets such as the
      telecommunication and banking industries, implementing customer churn prediction
      models that perform well and in accordance with the business goals is vital. The
      expected maximum profit (EMP) measure is tailored toward this problem by taking
      into account the costs and benefits of a retention campaign and estimating its
      worth for the organization. Unfortunately, the measure assumes fixed and equal
      customer lifetime value (CLV) for all customers, which has been shown to not
      correspond well with reality. In this article, we extend the EMP measure to take
      into account the variability in the lifetime values of customers, thereby basing
      it on individual characteristics. We demonstrate how to incorporate the
      heterogeneity of CLVs when CLVs are known, when their prior distribution is
      known, and when neither is known. By taking into account individual CLVs, our
      proposed approach of measuring model performance gives novel insights when
      deciding on a customer retention campaign. The method is dependent on the
      characteristics of the customer base as is compliant with modern business
      analytics and accommodates the data-driven culture that has manifested itself
      within organizations.

PMID- 29570413
TI  - Special Issue on Profit-Driven Analytics.

PMID- 29570414
TI  - Geospatial Analytics in Retail Site Selection and Sales Prediction.
AB  - Studies have shown that certain features from geography, demography, trade area,
      and environment can play a vital role in retail site selection, largely due to
      the impact they asserted on retail performance. Although the relevant features
      could be elicited by domain experts, determining the optimal feature set can be
      intractable and labor-intensive exercise. The challenges center around (1) how to
      determine features that are important to a particular retail business and (2) how
      to estimate retail sales performance given a new location? The challenges become
      apparent when the features vary across time. In this light, this study proposed a
      nonintervening approach by employing feature selection algorithms and
      subsequently sales prediction through similarity-based methods. The results of
      prediction were validated by domain experts. In this study, data sets from
      different sources were transformed and aggregated before an analytics data set
      that is ready for analysis purpose could be obtained. The data sets included data
      about feature location, population count, property type, education status, and
      monthly sales from 96 branches of a telecommunication company in Malaysia. The
      finding suggested that (1) optimal retail performance can only be achieved
      through fulfillment of specific location features together with the surrounding
      trade area characteristics and (2) similarity-based method can provide solution
      to retail sales prediction.

PMID- 29570416
TI  - FraudBuster: Reducing Fraud in an Auto Insurance Market.
AB  - Nonstandard insurers suffer from a peculiar variant of fraud wherein an
      overwhelming majority of claims have the semblance of fraud. We show that state
      of-the-art fraud detection performs poorly when deployed at underwriting. Our
      proposed framework "FraudBuster" represents a new paradigm in predicting segments
      of fraud at underwriting in an interpretable and regulation compliant manner. We
      show that the most actionable and generalizable profile of fraud is represented
      by market segments with high confidence of fraud and high loss ratio. We show how
      these segments can be reported in terms of their constituent policy traits,
      expected loss ratios, support, and confidence of fraud. Overall, our predictive
      models successfully identify fraud with an area under the precision-recall curve
      of 0.63 and an f-1 score of 0.769.

PMID- 29570415
TI  - A Literature Survey and Experimental Evaluation of the State-of-the-Art in Uplift
      Modeling: A Stepping Stone Toward the Development of Prescriptive Analytics.
AB  - Prescriptive analytics extends on predictive analytics by allowing to estimate an
      outcome in function of control variables, allowing as such to establish the
      required level of control variables for realizing a desired outcome. Uplift
      modeling is at the heart of prescriptive analytics and aims at estimating the net
      difference in an outcome resulting from a specific action or treatment that is
      applied. In this article, a structured and detailed literature survey on uplift
      modeling is provided by identifying and contrasting various groups of approaches.
      In addition, evaluation metrics for assessing the performance of uplift models
      are reviewed. An experimental evaluation on four real-world data sets provides
      further insight into their use. Uplift random forests are found to be
      consistently among the best performing techniques in terms of the Qini and Gini
      measures, although considerable variability in performance across the various
      data sets of the experiments is observed. In addition, uplift models are
      frequently observed to be unstable and display a strong variability in terms of
      performance across different folds in the cross-validation experimental setup.
      This potentially threatens their actual use for business applications. Moreover,
      it is found that the available evaluation metrics do not provide an intuitively
      understandable indication of the actual use and performance of a model.
      Specifically, existing evaluation metrics do not facilitate a comparison of
      uplift models and predictive models and evaluate performance either at an
      arbitrary cutoff or over the full spectrum of potential cutoffs. In conclusion,
      we highlight the instability of uplift models and the need for an application
      oriented approach to assess uplift models as prime topics for further research.

PMID- 29570417
TI  - Reduction of Marek's Disease Virus Infection by Toll-Like Receptor Ligands in
      Chicken Embryo Fibroblast Cells.
AB  - Evolutionarily conserved pattern recognition receptors, including Toll-like
      receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) that
      are present in microbes. PAMPs induce several pathways downstream of TLRs that
      lead to induction of antiviral responses. The objective of this study was to
      investigate the stimulatory effect of various PAMPs (in the form of TLR ligands)
      in reducing Marek's disease virus (MDV) infection in chicken embryo fibroblast
      cells (CEFs). To this end, CEFs were pretreated with Pam3CSK4, Poly(IC),
      lipopolysaccharide (LPS), and CpG ODN as TLR2, TLR3, TLR4, and TLR21 ligands,
      respectively for 24 h followed by infection with MDV. The results indicated that
      pretreatment with Poly(IC) resulted in a robust reduction (by about 81%) of MDV
      infection in CEFs at 96 h postinfection while a moderate reduction was observed
      with treatment of Pam3CSK4 (35%), LPS (26%), and CpG ODN (23%) PAMPs.
      Transcriptional analysis of gene expression in CEFs demonstrated that all TLR
      ligand treatments and MDV infection significantly increased the expression of
      type I interferons, interleukin (IL)-1beta, interferon regulatory factor 7
      (IRF7), interferon induced protein with tetratricopeptide repeats 5 (IFIT5), and
      myxoma-resistance protein (Mx). Further studies are needed to explore the
      mechanism by which PAMPs, particularly the TLR3 ligands could reduce MDV
      infection in CEFs, which may play an important role in controlling the
      replication of MDV in chicken.

PMID- 29570418
TI  - Histological and Thermometric Examination of Soft Tissue De-Epithelialization
      Using Digitally Controlled Er:YAG Laser Handpiece: An Ex Vivo Study.
AB  - OBJECTIVE: The purpose of this study was histological and thermometric
      examination of soft tissue de-epithelialization using digitally controlled laser
      handpiece (DCLH) - X-Runner. BACKGROUND DATA: Commonly used techniques for de
      epithelialization include scalpel, abrasion with diamond bur, or a combination of
      the two. Despite being simple, inexpensive and effective, these techniques are
      invasive and may produce unwanted side effects. It is important to look for
      alternative techniques using novel tools, which are minimally invasive and
      effective. MATERIALS AND METHODS: 114 porcine samples sized 6 * 6 mm were
      collected from the attached gingiva (AG) of the alveolar process of the mandible
      using 15C scalpel blade. The samples were irradiated by means of Er:YAG laser
      (LightWalker, Fotona, Slovenia), using X-Runner and HO2 handpieces at different
      parameters; 80, 100, and 140 mJ/20 Hz in time of 6 or 16 sec, respectively. The
      temperature was measured with a K-type thermocouple. For the histopathological
      analysis of efficiency of epithelium removal and thermal injury, 3 random samples
      were de-epithelialized with an HO2 handpiece, and 9 random samples with an X
      Runner handpiece with different parameters. For the samples irradiated with DCLH,
      we have used three different settings, which resulted in removing 1 to 3 layers
      of the soft tissue. The efficiency of epithelium removal and the rise of
      temperature were analyzed. RESULTS: DCLH has induced significantly lower
      temperature increase compared with HO2 at each energy to frequency ratio. The
      histological examination revealed total epithelium removal when HO2 handpiece was
      used at 100 and 140 mJ/20 Hz and when DCLH was used for two- and threefold lasing
      at 80, 100, and 140 mJ/20 Hz. CONCLUSIONS: Er:YAG laser with DCLH handpiece may
      be an efficient tool in epithelium removal without excessive thermal damage.

PMID- 29570420
TI  - Reply to M. Melo et al.

PMID- 29570419
TI  - Age-Associated Mortality Risk in Papillary Thyroid Cancer: Does BRAF Make a Real
      Difference?

PMID- 29570421
TI  - Five-Year Follow-Up of Nivolumab in Previously Treated Advanced Non-Small-Cell
      Lung Cancer: Results From the CA209-003 Study.
AB  - Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1)
      inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated
      advanced non-small-cell lung cancer (NSCLC). We report 5-year follow-up results
      from an early phase I study of nivolumab in this patient population and describe
      characteristics of 5-year survivors. Patients and Methods Patients with
      pretreated, advanced NSCLC received nivolumab 1, 3, or 10 mg/kg every 2 weeks in
      8-week cycles for up to 96 weeks. OS from the time of first dose was estimated by
      the Kaplan-Meier method. Results The estimated 5-year OS rate was 16% for all
      treated patients (N = 129); 5-year OS rates were similar for squamous (16%) and
      nonsquamous (15%) NSCLC. Of 16 5-year survivors, most (88%) were known current or
      former smokers. Of 10 5-year survivors with quantifiable PD-1 ligand 1
      expression, 70% had >= 1% PD-1 ligand 1 expression at baseline. Twelve 5-year
      survivors (75%) achieved a partial response to nivolumab per Response Evaluation
      Criteria in Solid Tumors, version 1.0, and two each (12%) had stable disease and
      progressive disease as best response. Nine 5-year survivors (56%) completed the
      maximum 96 weeks of nivolumab; four (25%) discontinued owing to adverse events
      and three (19%) owing to disease progression. As of a November 2016 database
      lock, 12 5-year survivors (75%) received no subsequent therapy and were without
      evidence of progressive disease at last follow-up. Conclusions Nivolumab
      treatment resulted in long-term OS and durable responses in a proportion of
      patients with pretreated advanced NSCLC. Long-term survivors had diverse baseline
      and on-treatment characteristics.

PMID- 29570422
TI  - Aging Is a Sticky Business.
AB  - OBJECTIVE: The objective of this work is to put forward a mechanism by which low
      level light [red-to near infrared (NIR) laser or light emitting diodes (LED)] is
      instrumental in the process of accelerating the healing of wounds. BACKGROUND
      DATA: Interaction modalities of low-level light with oxidatively stressed cells
      and tissues are the focus of intense research efforts. Several models of the
      light/cell-interaction mechanism have been proposed. In the most popular model,
      cytochrome c oxidase is believed to play the role of the principal acceptor for
      red-to NIR photons. METHODS: Using as an illustrative example the successful LED
      treatment of an edematous limb ulcer, the results of recent in vitro tests and
      complementary laboratory experiments are presented and discussed. RESULTS: The
      most plausible mechanism of biostimulatory effect of red-to NIR light consists of
      its impact on the nanoscopic interfacial water layers in mitochondria and the
      extracellular matrix (ECM) where mitochondrial reactive oxygen species (ROS)
      induce an increase in the viscosity of the water layers bound to the
      predominantly hydrophilic surfaces in the intramitochondrial space as well as the
      ECM, where the process progressively propagates with age. The biostimulatory
      effect of red-to NIR light consists of counteracting the ROS-induced elevation of
      interfacial water viscosities, thereby instantly restoring the normal
      mitochondrial function, including the synthesis of adenosine triphosphate (ATP)
      by the rotary motor (ATP synthase). CONCLUSIONS: An understanding of the
      mechanism of interaction of red-to NIR light with mitochondria, cells, and
      tissues safeguards progress in the field of low-level light therapy (LLLT) and
      puts us in the position to design better therapies.

PMID- 29570423
TI  - Current and Future Trends in Adipose Stem Cell Differentiation into Neuroglia.
AB  - BACKGROUND: Neurological diseases and disorders pose a challenge for treatment
      and rehabilitation due to the limited capacity of the nervous system to repair
      itself. Adipose stem cells (ASCs) are more pliable than any adult stem cells and
      are capable of differentiating into non-mesodermal tissues, including neurons.
      Transdifferentiating ASCs to specific neuronal lineage cells enables us to
      deliver the right type of cells required for a replacement therapy into the
      nervous system. METHODS: Several methodologies are being explored and tested to
      differentiate ASCs to functional neurons and glia with cellular factors and
      chemical compounds. However, none of these processes and prototypes has been
      wholly successful in changing the cellular structure and functional status of
      ASCs to become identical to neuroglial cells. In addition, successful integration
      and functional competence of these cells for use in clinical applications remain
      problematic. Photobiomodulation or low-level laser irradiation has been
      successfully applied to not only improve ASC viability and proliferation but has
      also shown promise as a possible enhancer of ASC differentiation. CONCLUSIONS:
      Studies have shown that photobiomodulation improves the use of stem cell
      transplantation for neurological applications. This review investigates current
      neuro-differentiation inducers and suitable methodologies, including
      photobiomodulation, utilizing ASCs for induction of differentiation into neuronal
      lineages.

PMID- 29570426
TI  - Evaluation of a new ballistic vest design for compliance with Standard No. PN-V
      87000:2011 using physiological tests.
AB  - Research into newly developed ballistic vests to be worn by police officers under
      clothing was carried out with air temperature conditions of +20  degrees C. A
      ballistic vest should incorporate protective features, comfort and ergonomics.
      The thermal strain on users who wore the vests was evaluated as an average and
      individually, after they had been conditioned in high (+50  degrees C), low (-40 
      degrees C) or neutral (+20  degrees C) air temperatures, while performing various
      occupational activities. Research involved six police officers aged 36-42 years,
      who wore civilian clothing used in moderate environmental conditions. During the
      tests, physiological parameters (internal temperature, local skin temperatures
      and amount of sweat secreted) were determined. The ease of doing exercises while
      wearing the vests, vest service and level of discomfort in use were assessed.
      Research showed that the vests tested, both as an average and individually, meet
      the requirements of Standard No. PN-V-87000:2011 (clause 4.5).

PMID- 29570425
TI  - A kindergarten-based child health promotion program: the Adapted National
      Aeronautics and Space Administration (NASA) Mission X for improving physical
      fitness in South Korea.
AB  - BACKGROUND: Effective and sustainable intervention programs are needed to promote
      physical activity (PA) in children. OBJECTIVES: To adapt the NASA Mission X:
      Train Like an Astronaut program for use with South Korean children, and to
      evaluate its feasibility and effectiveness for promoting children's physical
      fitness. METHODS: Children 5 years old ( n = 212) and their parents were
      recruited from three kindergartens in three cities to participate in a 6-week
      intervention program in fall 2014. We assessed the children's PA and related
      changes, and parental changes in attitude and beliefs, after participation in the
      intervention. RESULTS: Girls reported less PA than boys (40.7 vs. 59.0, p <
      0.01). Children with a normal body mass index (BMI) were more likely to be active
      than underweight children (< 10 percentile) or overweight children (? 85
      percentile). After the intervention, about one-half of the children had increased
      their level of PA (49.4%), increased interest in PA (59.1%) and found
      psychological need satisfaction in exercise (52.6%). The majority of parents
      became aware of the necessity of childhood PA (94.2%), their child's PA
      capability (64.3%), and the relationship of PA with their children's self-esteem
      (79.9%). CONCLUSIONS: The adapted NASA Mission X program was feasible and
      effective in promoting PA in kindergarteners, and also improved their parents'
      attitude and beliefs about children's PA in South Korea. This study provided a
      model for promoting childhood health through child care and educational settings.

PMID- 29570427
TI  - "It's Relentless": Providers' Experience of Pediatric Chronic Critical Illness.
AB  - BACKGROUND: Children with chronic critical illness (CCI), those children with
      repeated and prolonged hospitalizations along with technology-dependence or
      multiple organ system involvement, are increasing in number. The intensive daily
      needs of these children, during hospitalization and at home, affect both
      clinicians and families. OBJECTIVE: To assess clinician experiences of burnout
      and clinician perceptions of family burnout in caring for children with CCI.
      DESIGN: Semistructured interviews with 44 stakeholders known for pediatric CCI
      expertise were audio-recorded and transcribed. Participants characterized their
      experiences with provider and family burnout. SETTING/SUBJECTS: Stakeholders were
      from five metropolitan areas, representing a variety of professions (i.e.,
      inpatient/outpatient clinicians, home health providers, and policy
      professionals). MEASUREMENTS: Content analysis was performed on interview
      transcripts. RESULTS: Participants reported that both clinicians and families
      caring for children with CCI experience some level of burnout, although
      stakeholders note that families may experience burnout differently than
      clinicians. Burnout results from the following: (1) escalating daily care needs;
      (2) intense relationships between clinicians and families; (3) uncertain
      outcomes; (4) feeling unprepared to care for children with complicated medical
      needs; and (5) the stress and emotional toll of caring for a child with CCI.
      CONCLUSIONS: Managing the medical needs of children with CCI can be associated
      with clinician and parent burnout. Strategies to support clinicians and families
      are needed to ensure high quality of care for these children, as well as maintain
      an appropriate number of clinical providers for this vulnerable subset of
      children with medical complexity.

PMID- 29570428
TI  - Intravascular Cooling Catheter-Related Venous Thromboembolism After Hypothermia:
      A Case Report and Review of the Literature.
AB  - Fifty-four year-old man with recent history of myocardial infarction and a
      percutaneous coronary intervention who suffered a ventricular fibrillation arrest
      at home. He was resuscitated in the field. His heart rhythm was in atrial
      fibrillation. The cardiac catheterization showed a patent stent from his previous
      myocardial infarction and no new occlusions. He subsequently underwent
      hypothermia protocol using the Alsius CoolGard 3000 Temperature Control System
      and Icy Catheter. Heparin drip was started for atrial fibrillation 36 hours after
      catheter insertion and became therapeutic 2 hours before the end of cooling
      maintenance phase. Heparin drip was stopped 4 hours into the rewarming phase
      because of spontaneous conversion to sinus rhythm. Subcutaneous heparin was
      resumed for deep venous thrombosis prophylaxis. He was extubated to room air
      after hypothermia protocol. The cooling catheter was removed 88 hours after
      insertion. Within 1 minute of catheter removal, his oxygen saturation dropped to
      80%. Transthoracic echocardiogram showed a mobile thrombus in the right atrium
      prolapsing into the right ventricle. Computer tomography angiography of the chest
      confirmed a large saddle embolus. Ninety minutes later, patient went into cardiac
      arrest with pulseless electrical activity while he was being considered for
      surgical embolectomy, but he could not be resuscitated. The temporal relationship
      of the catheter removal and his acute clinical decompensation led to believe that
      this was an intravascular cooling catheter (ICC)-related event. Providers should
      be cognizant of the complications of central venous catheters such as thrombosis
      formation, as it could lead to fatal pulmonary embolism. Physicians should
      promote frequent assessment of the access site(s) during routine physical
      examinations and potentially use point of care vascular ultrasound in high-risk
      cases to rule out a catheter-associated thrombus before catheter removal.

PMID- 29570429
TI  - Changes in Social Integration Predict Changes in Physical Activity: A 25-Year
      Prospective Study.
AB  - BACKGROUND: Social relationships are among the strongest predictors of health.
      The extent to which one is embedded in social networks, also referred to as
      social integration, has been associated with physical activity in short-term
      longitudinal and cross-sectional studies. How changes in social integration
      impact physical activity over longer periods of time is not well understood.
      METHODS: Longitudinal data from 5 waves of the Americans' Changing Lives study
      were used (wave 1: n = 3617; wave 5: n = 1427). Data were modeled using latent
      growth curves to understand the trajectories of social integration and physical
      activity, separately. Latent interlocking growth curve methods were used to
      understand if and how changes in social integration predicted changes in physical
      activity. RESULTS: Physical activity did not change over the 25-year period (P =
      .68). Social integration significantly decreased (P = .025). Changes in social
      integration predicted changes in physical activity (beta = 0.12, P < .05).
      CONCLUSIONS: Changes in how often adults speak to family and friends predict
      changes in physical activity across a 25-year period. Group- and social network
      focused physical activity research, advocacy, and interventions are warranted.

PMID- 29570430
TI  - Test of Responsiveness and Sensitivity of the Questionnaire "Lymphedema Quality
      of Life Inventory".
AB  - BACKGROUND: Lymphedema may affect patients' health-related quality of life
      (HRQoL) and thus a disease-specific questionnaire is needed. The Lymphedema
      Quality of life Inventory (LyQLI) has been tested for reliability and validity.
      The purpose of this study was to test the LyQLI for responsiveness and
      sensitivity. METHODS AND RESULTS: The study participants were patients with
      lymphedema in the upper or lower limb, attending a Swedish rehabilitation program
      (RP) and undergoing conservative treatment without surgery (RP-sample), or
      undergoing liposuction (LS) in Australia, Scotland, and Sweden (LS-sample). Mean
      values for the three LyQLI domains (physical, psychosocial, and practical) were
      calculated before and 1 month after intervention, and the paired t-test was used
      to detect group differences. Responsiveness was calculated using standardized
      response mean (SRM), and sensitivity was analyzed with box plots and an
      independent t-test to detect group differences. Eighteen patients in the RP
      sample and 50 in the LS-sample were studied, and both samples demonstrated
      increased HRQoL after intervention. The changes were significant in all domains,
      except for the practical domain in the RP-sample. The SRM for the three LyQLI
      domains (physical, psychosocial, and practical) were 0.8, 0.8, and 0.4,
      respectively, in the RP-sample and 0.7, 1.2, and 0.9 in the LS-sample.
      Statistical testing indicated that the LyQLI was sensitive enough to reveal
      differences between patient groups. CONCLUSIONS: LyQLI responsiveness and
      sensitivity indicated that the tool can be used to evaluate patients undergoing
      conservative or surgical lymphedema treatments.

PMID- 29570432
TI  - Transcriptome-seq provides insights into sex-preference pattern of gene
      expression between testis and ovary of the crucifix crab ( Charybdis feriatus).
AB  - The crucifix crab, Charybdis feriatus, which mainly inhabits Indo-Pacific region,
      is regarded as one of the most high-potential species for domestication and
      incorporation into the aquaculture sector. However, the regulatory mechanisms of
      sex determination and differentiation of this species remain unclear. To identify
      candidate genes involved in sex determination and differentiation, high
      throughput sequencing of transcriptome from the testis and ovary of C. feriatus
      was performed by the Illumina platform. After removing adaptor primers, low
      quality sequences and very short (<50 nt) reads, we obtained 80.9 million and
      66.2 million clean reads from testis and ovary, respectively. A total of 86,433
      unigenes were assembled, and ~43% (37,500 unigenes) were successfully annotated
      to the NR, NT, Swiss-Prot, KEGG, COG, GO databases. By comparing the testis and
      ovary libraries, we obtained 27,636 differentially expressed genes. Some
      candidate genes involved in the sex determination and differentiation of C.
      feriatus were identified, such as vasa, pgds, vgr, hsp90, dsx-f, fem-1, and gpr.
      In addition, 88,608 simple sequence repeats were obtained, and 61,929 and 77,473
      single nucleotide polymorphisms from testis and ovary were detected,
      respectively. The transcriptome profiling was validated by quantitative real-time
      PCR in 30 selected genes, which showed a good consistency. The present study is
      the first high-throughput transcriptome sequencing of C. feriatus. These findings
      will be useful for future functional analysis of sex-associated genes and
      molecular marker-assisted selections in C. feriatus.

PMID- 29570431
TI  - G protein-coupled receptor kinase-2-deficient mice are protected from dextran
      sodium sulfate-induced acute colitis.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays
      a key role in different disease processes. Previously, we showed that GRK2
      knockdown enhances wound healing in colonic epithelial cells. Therefore, we
      hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate
      (DSS)-induced acute colitis. To test this, we administered DSS to wild-type
      (GRK2+/+) and GRK2 heterozygous (GRK+/-) mice in their drinking water for 7 days.
      As predicted, GRK2+/- mice were protected from colitis as demonstrated by
      decreased weight loss (20% loss in GRK2+/+ vs. 11% loss in GRK2+/-). lower
      disease activity index (GRK2+/+ 9.1 vs GRK2+/- 4.1), and increased colon lengths
      (GRK2+/+ 4.7 cm vs GRK2+/- 5.3 cm). To examine the mechanisms by which GRK2+/-
      mice are protected from colitis, we investigated expression of inflammatory genes
      in the colon as well as immune cell profiles in colonic lamina propria,
      mesenteric lymph node, and in bone marrow. Our results did not reveal differences
      in immune cell profiles between the two genotypes. However, expression of
      inflammatory genes was significantly decreased in DSS-treated GRK2+/- mice
      compared with GRK2+/+. To understand the mechanisms, we generated myeloid
      specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to
      whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was
      sufficient for the protection from DSS-induced colitis. Together our results
      indicate that deficiency of GRK2 protects mice from DSS-induced colitis and
      further suggests that the mechanism of this effect is likely via GRK2 regulation
      of inflammatory genes in the myeloid cells.

PMID- 29570434
TI  - Hemerodrome: A Messenger and Medicine.

PMID- 29570433
TI  - Targeted disruption of regulated endocrine-specific protein ( Resp18) in Dahl
      SS/Mcw rats aggravates salt-induced hypertension and renal injury.
AB  - Hypertension is a classic example of a complex polygenic trait, impacted by
      quantitative trait loci (QTL) containing candidate genes thought to be
      responsible for blood pressure (BP) control in mammals. One such mapped locus is
      on rat chromosome 9, wherein the proof for a positional candidate gene, regulated
      endocrine-specific protein-18 ( Resp18) is currently inadequate. To ascertain the
      status of Resp18 as a BP QTL, a custom targeted gene disruption model of Resp18
      was developed on the Dahl salt-sensitive (SS) background. As a result of this
      zinc-finger nuclease (ZFN)-mediated disruption, a 7 bp deletion occurred within
      exon 3 of the Resp18 locus. Targeted disruption of Resp18 gene locus in SS rats
      decreases its gene expression in both heart and kidney tissues regardless of
      their dietary salt level. Under a high-salt dietary regimen, both systolic and
      diastolic BP of Resp18mutant rats were significantly increased compared with SS
      rats. Resp18mutant rats demonstrated increased renal damage, as evidenced by
      higher proteinuria and increased renal fibrosis compared with SS rats.
      Furthermore, under a high-salt diet regimen, the mean survival time of
      Resp18mutant rats was significantly reduced compared with SS rats. These findings
      serve as evidence in support of Resp18 as a gene associated with the development
      of hypertension and renal disease.

PMID- 29570435
TI  - Development of a Surveillance Definition for United States-Mexico Binational
      Cases of Tuberculosis.
AB  - OBJECTIVES: Consistently collected binational surveillance data are important in
      advocating for resources to manage and treat binational cases of tuberculosis
      (TB). The objective of this study was to develop a surveillance definition for
      binational (United States-Mexico) cases of TB to assess the burden on US TB
      program resources. METHODS: We collaborated with state and local TB program staff
      members in the United States to identify characteristics associated with
      binational cases of TB. We collected data on all cases of TB from 9 pilot sites
      in 5 states (Arizona, California, Colorado, New Mexico, and Texas) during January
      1-June 30, 2014, that had at least 1 binational characteristic (eg, "crossed
      border while on TB treatment" and "received treatment in another country,
      coordinated by an established, US-funded, binational TB program"). A workgroup of
      US state, local, and federal partners reviewed results and used them to develop a
      practical surveillance definition. RESULTS: The pilot sites reported 87 cases of
      TB with at least 1 binational characteristic during the project period. The
      workgroup drafted a proposed surveillance definition to include 2 binational
      characteristics: "crossed border while on TB treatment" (34 of 87 cases, 39%) and
      "received treatment in another country, coordinated by an established, US-funded,
      binational TB program" (26 of 87 cases, 30%). Applying the new proposed
      definition, 39 of 87 pilot cases of TB (45%) met the definition of binational.
      CONCLUSION: Input from partners who were responsible for the care and treatment
      of patients who cross the United States-Mexico border was crucial in defining a
      binational case of TB.

PMID- 29570439
TI  - TAKING IT TO THE GUT.
AB  - SARAH WEBB EXAMINES HOW GASTROINTESTINAL ORGANOIDS ARE TRANSFORMING OUR
      UNDERSTANDING OF BIOLOGY AND HELPING PATIENTS.

PMID- 29570440
TI  - BUILDING THE FUTURE FROM 3D BLUEPRINTS.
AB  - 3D printed biomaterials are increasingly used in cell cultures and drug screens.
      Given the ease of creating artificial tissues, will this technique revolutionize
      biomedicine and organ implants in the future?

PMID- 29570436
TI  - Associations Between Comorbid Health Conditions and Quit Outcomes Among Smokers
      Enrolled in a State Quitline, Arizona, 2011-2016.
AB  - OBJECTIVE: Smokers with comorbid health conditions have a disproportionate burden
      of tobacco-related death and disease. A better understanding of differences in
      quit rates among smokers with comorbid health conditions can guide tailoring of
      quitline services for subgroups. The objective of this study was to examine self
      reported tobacco cessation rates among Arizona Smokers' Helpline callers with
      chronic health conditions (CHCs) and/or a mental health condition (MHC). METHODS:
      We analyzed data from quitline telephone callers (n = 39 779) who enrolled in and
      completed at least 1 behavioral counseling session (ie, coaching call). We
      categorized callers as CHC only (cardiovascular disease/respiratory
      related/cancer; 32%), MHC only (eg, mood/anxiety/substance dependence; 13%), CHC
      + MHC (25%), or no comorbid condition (30%). We assessed 30-day abstinence at 7
      month follow-up for 16 683 clients (41.9%). We used logistic regression analysis
      to test associations between comorbidity and quit outcomes after controlling for
      relevant variables (eg, nicotine dependence). RESULTS: Overall quit rates were
      45.4% for those with no comorbid condition, 43.3% for those with a CHC only,
      37.0% for those with an MHC only, and 33.3% for those with CHC + MHC. Compared
      with other groups, the CHC + MHC group had the lowest odds of quitting (adjusted
      odds ratio = 0.60; 95% confidence interval, 0.52-0.69). CONCLUSION: Having a
      comorbid condition was associated with lower quit rates, and smokers with co
      occurring CHCs and MHCs had the lowest quit rates. Quitlines should evaluate more
      intensive, evidence-driven, tailored services for smoking cessation among callers
      with comorbid conditions.

PMID- 29570441
TI  - Restricted exchange microenvironments for cell culture.
AB  - Metabolite diffusion in tissues produces gradients and heterogeneous
      microenvironments that are not captured in standard 2D cell culture models. Here
      we describe restricted exchange environment chambers (REECs) in which diffusive
      gradients are formed and manipulated on length scales approximating those found
      in vivo. In REECs, cells are grown in 2D in an asymmetric chamber (<50 MUL)
      formed between a coverglass and a glass bottom cell culture dish separated by a
      thin (~100 MUm) gasket. Diffusive metabolite exchange between the chamber and
      bulk media occurs through one or more openings micromachined into the coverglass.
      Cell-generated concentration gradients form radially in REECs with a single round
      opening (~200 MUm diameter). At steady state only cells within several hundred
      micrometers of the opening experience metabolite concentrations that permit
      survival which is analogous to diffusive exchange near a capillary in tissue. The
      chamber dimensions, the openings' shape, size, and number, and the cellular
      density and metabolic activity define the gradient structure. For example, two
      parallel slots above confluent cells produce the 1D equivalent of a spheroid.
      Using REECs, we found that fibroblasts align along the axis of diffusion while
      MDCK cells do not. MDCK cells do, however, exhibit significant morphological
      variations along the diffusive gradient.

PMID- 29570442
TI  - Improved spot morphology for printed glycan arrays.
AB  - Despite considerable success studying glycan-binding proteins using printed
      glycan arrays (PGAs), unambiguous quantitation of spot intensities by fluorescent
      readers remains a challenge. The main obstacles are the varying spot shape and
      size and in-spot fluorescence distribution caused by uneven drying of the printed
      drops. Two methods have been suggested for solving this problem: using polymeric
      glycoconjugates, which makes it possible to equalize the physicochemical
      properties (hydrophobicity, charge, and size) of different glycans, and applying
      a glycan solution on a slide coated with a thin oil mask, which hinders
      evaporation of the drop. Both approaches yield spots with similar sizes and an
      even distribution of the signal across the spot and are likely to be useful for
      improving the prints of other classes of molecules.

PMID- 29570443
TI  - Single step production of Cas9 mRNA for zygote injection.
AB  - Production of Cas9 mRNA in vitro typically requires the addition of a 5' cap and
      3' polyadenylation. A plasmid was constructed that harbored the T7 promoter
      followed by the EMCV IRES and a Cas9 coding region. We hypothesized that the use
      of the metastasis associated lung adenocarcinoma transcript 1 (Malat1) triplex
      structure downstream of an IRES/Cas9 expression cassette would make
      polyadenylation of in vitro produced mRNA unnecessary. A sequence from the
      mMalat1 gene was cloned downstream of the IRES/Cas9 cassette described above. An
      mRNA concentration curve was constructed with either commercially available Cas9
      mRNA or the IRES/ Cas9/triplex, by injection into porcine zygotes. Blastocysts
      were genotyped to determine if differences existed in the percent of embryos
      modified. The concentration curve identified differences due to concentration and
      RNA type injected. Single step production of Cas9 mRNA provides an alternative
      source of Cas9 for use in zygote injections.

PMID- 29570444
TI  - Thioclava electrotropha sp. nov., a versatile electrode and sulfur-oxidizing
      bacterium from marine sediments.
AB  - A taxonomic and physiologic characterization was carried out on Thioclava strain
      ElOx9T, which was isolated from a bacterial consortium enriched on electrodes
      poised at electron donating potentials. The isolate is Gram-negative, catalase
      positive and oxidase-positive; the cells are motile short rods. The bacterium is
      facultatively anaerobic with the ability to utilize nitrate as an electron
      acceptor. Autotrophic growth with H2 and S0 (oxidized to sulfate) was observed.
      The isolate also grows heterotrophically with organic acids and sugars. Growth
      was observed at salinities from 0 to 10% NaCl and at temperatures from 15 to 41 
      degrees C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      the strain belongs in the genus Thioclava; it had the highest sequence similarity
      of 98.8 % to Thioclava atlantica 13D2W-2T, followed by Thioclava dalianensis
      DLFJ1-1T with 98.5 % similarity, Thioclava pacifica TL 2T with 97.7 % similarity,
      and then Thioclava indica DT23-4T with 96.9 %. All other sequence similarities
      were below 97 % to characterized strains. The digital DNA-DNA hybridization
      estimated when compared to T. atlantica 13D2W-2T, T. dalianensis DLFJ1-1T, T.
      pacifica TL 2T and T. indica DT23-4T were 15.8+/-2.1, 16.7+2.1, 14.3+/-1.9 and
      18.3+/-2.1 %. The corresponding average nucleotide identity values between these
      strains were determined to be 65.1, 67.8, 68.4 and 64.4 %, respectively. The G+C
      content of the chromosomal DNA is 63.4 mol%. Based on these results, a novel
      species Thioclava electrotropha sp. nov. is proposed, with the type strain ElOx9T
      (=DSM 103712T=ATCC TSD-100T).

PMID- 29570445
TI  - Dokdonia aurantiaca sp. nov., isolated from seaweed Zostera marina.
AB  - A non-motile, orange-coloured and rod-shaped bacterial strain, designated strain
      ZOW29T, was isolated from a seaweed sample collected from the South Sea, Republic
      of Korea. Cells were Gram-stain-negative, aerobic and non-motile. The isolate
      required sea salts for growth. Carotenoid pigment was produced. A phylogenetic
      tree based on 16S rRNA gene sequences showed that strain ZOW29T forms an
      evolutionary lineage within the radiation enclosing the members of the genus
      Dokdonia with Dokdonia diaphoros MSKK-32T, Dokdonia eikasta PMA-26Tand Dokdonia
      donghaensis DSW-1T (97.1 % sequence similarity each) as its nearest neighbours.
      The DNA-DNA relatedness values between strain ZOW29T and these four type strains
      were 35-48 %. The major fatty acids were iso-C15:0, iso-C17 : 0 3-OH and iso-C15
      : 1 G. Strain ZOW29T contained MK-6 and phosphatidylethanolamine, an unidentified
      aminolipid and an unidentified polar lipid as the only isoprenoid quinone and the
      major polar lipids, respectively. The DNA G+C content of strain ZOW29T was 38
      mol%. On the basis of polyphasic characterization, it is suggested that the
      isolate represents a novel species of the genus Dokdonia, for which the name
      Dokdonia aurantiaca sp. nov. (type strain, ZOW29T=KCTC 52956T=JCM 32295T) is
      proposed.

PMID- 29570446
TI  - Use of an immunochromatographic assay for rapid identification of Mycobacterium
      tuberculosis complex clinical isolates in routine diagnosis.
AB  - Accurate identification of Mycobacterium tuberculosis complex (MTBC) isolates is
      essential for tuberculosis (TB) control, especially in a high-burden country such
      as Brazil. Conventional identification methods are laborious and time-consuming,
      while rapid molecular methods are expensive and require skilled personnel and
      appropriate physical laboratory infrastructure. Immunochromatographic assays
      (ICAs) have been shown to provide a rapid and reliable TB diagnosis at a low
      cost. The use of the SD Bioline TB Ag MPT64 ICA (MPT64 assay) for rapid
      identification of MTBC clinical isolates in the routine diagnosis of a large
      volume reference TB laboratory was evaluated. We analysed 375 isolates on solid
      and liquid media concurrently with conventional phenotypic methods, the PRA-hsp65
      molecular technique and the MPT64 assay. The sensitivity, specificity and
      accuracy of the ICA were 97.7, 100 and 98.1 %, respectively. The MPT64 assay
      yielded rapid and accurate results, enabling the treatment to be initiated early
      and also impacting on TB control.

PMID- 29570447
TI  - Aged coconut oil with a high peroxide value induces oxidative stress and tissue
      damage in mercury-treated rats.
AB  - Background Exposure to mercury (Hg) and the ingestion of peroxidized edible oil
      represent a health risk. This study evaluated the effects of peroxidized coconut
      oil (CO) on the liver and kidney of rats treated with Hg. Methods Male albino
      Wistar rats were administered HgCl2 and CO separately or as a combination for 21
      days. The concentrations of glutathione (GSH) and malondialdehyde (MDA), as well
      as the activities of superoxide dismutase (SOD) and catalase (CAT), which were
      used as markers of oxidative stress were measured in the liver and kidney
      homogenates. The activities of gamma glutamyl transferase (gamma-GT), lactate
      dehydrogenase (LDH) as well as the levels of bilirubin and creatinine (CREA) as
      markers of liver and kidney functions were analyzed in the serum. Results The
      level of MDA in the kidney and liver homogenates was significantly increased in
      the HgCl2, CO, and CO+HgCl2 groups when compared to control values (p<0.05).
      Liver SOD activity and GSH level were increased and CAT activity was decreased,
      whereas kidney GSH level and SOD activity were decreased and CAT activity was
      increased in the CO and CO+HgCl2 groups when compared to control values (p<0.05).
      The increase in CREA and bilirubin levels as well as gamma-GT and LDH activities
      observed in the CO+HgCl2 group when compared to the control values (p<0.05) were
      associated with pathological changes in both tissues, and were considered to be
      due to oxidative stress. Conclusions In summary, peroxidized CO and Hg alone or
      in combination induces oxidative damage in the liver and kidney of rats.

PMID- 29570448
TI  - A comparative study of the effect of stress on the cognitive parameters in women
      with increased body mass index before and after menopause.

PMID- 29570449
TI  - Effects of Trypanosoma brucei brucei infection and diminazene aceturate
      administration on the blood pressure, heart rate, and temperature of Wistar
      albino rats.
AB  - BACKGROUND: This study was carried out to determine the blood pressure changes in
      experimentally Trypanosoma brucei brucei-infected Wistar albino rats and
      diminazene aceturate-treated rats. METHODS: Twenty-four rats were purchased and
      divided into four groups consisting of six rats each. Control group (CON)
      received 0.5 mL of distilled water, i.m., infected but not treated group (INF)
      received 2*106 trypanosome/mL i.m., infected but diminazene aceturate-treated
      group (INFDIM) received 2*106 trypanosome/mL, 3.5 mg/kg, i.m.) and non-infected
      but diminazene aceturate-treated group (DIM) received 3.5 mg/kg, i.m. and served
      as negative control. The blood pressures were measured using a CODA 2(r) non
      invasive blood pressure monitor (Kent Scientific, USA). The results were compiled
      and statistical analysis was done with significance set at p>=0.05. RESULTS: The
      values of the blood pressure readings of the Trypanosoma-infected INF (137.0+/
      2.0 mmHg) and diminazene-treated rats INFDIM (125.0+/-7.5 mmHg) when compared to
      the control group (168.0+/-3.0 mmHg) were significantly lower (p<=0.05) at the
      end of day 7. The heart rate was also significantly reduced in the INF (403.5+/
      1.5 beats/min) and DIM (445.0+/-24 beats/min) groups of rats when compared with
      the control group (613.0+/-2.0 beats/min) at the end of day 8. CONCLUSION: The
      findings indicate the significant reduction in blood pressure and heart rates
      during Trypanosoma brucei brucei infection and with diminazene aceturate
      administration. Hence, caution should be exercised when treating trypanosome
      infected patients with diminazene aceturate.

PMID- 29570450
TI  - Neuroprotective effect of curcumin nanoparticles against rat model of status
      epilepticus induced by pilocarpine.

PMID- 29570452
TI  - Is pravastatin a milestone in the prevention and treatment of preeclampsia?

PMID- 29570451
TI  - Evaluating of beta-carotene role in ameliorating of favism-induced disturbances
      in blood and testis.

PMID- 29570453
TI  - Anencephaly and obstetric outcome beyond the age of viability.
AB  - Objective To review the obstetric impact and natural history of anencephalic
      pregnancies beyond the age of viability. Study design A retrospective chart
      review of all cases with a prenatal diagnosis of anencephaly who delivered after
      24 weeks' gestation during the period 1990 until 2016. Obstetric outcomes
      including mode of delivery, live births, shoulder dystocia, antepartum
      haemorrhage (APH), postpartum haemorrhage (PPH) and uterine rupture were studied.
      Results A total of 42 cases were studied. The average gestational age at
      diagnosis was 22 weeks (range 10-41). The average gestational age at birth was 36
      weeks (range 25-44 weeks). Induction of labour was performed in 55% (23/42) of
      the cases. Livebirths were documented in 40% (17/42) of the cases. The average
      birth weight was 1597+/-746 g. The rate of vaginal birth was 69% (29/42), the
      overall rate of caesarean section was 31% (13/42), with a primary caesarean
      section in 31% (4/13) and a repeat caesarean section in 69% (9/13) of the
      patients. There were two cases of shoulder dystocia. No other complications were
      encountered. Conclusion Overall, anencephaly is not associated with an increased
      risk of obstetric complications; however, there is a tendency towards delivery
      via repeated caesarean section in women with a previous uterine scar and
      anencephaly. The prenatal counselling of potential obstetric outcomes could be of
      robust value for parents who opt to continue with anencephalic pregnancies.

PMID- 29570454
TI  - Does ultrasound-guided intervention during repeat cesarean sections improve
      uterine scar architecture and reduce the number of scars? A prospective
      controlled clinical intervention trial.
AB  - Purpose To evaluate whether intraoperative ultrasound-guided detection and
      resection of the uterine scar during repeat/second cesarean can reduce the number
      of scars and improve uterine scar architecture. Materials and methods A
      prospective controlled clinical intervention trial was performed with the
      following groups: control group 1 (CS1-G): first cesarean; control group 2 (CS2
      G): second cesarean utilizing the usual procedure and intervention group (Int-G):
      repeat/second cesarean with intervention. Transvaginal ultrasound scans were
      performed 6-9 months after each cesarean. Both primary (double scarring rate) and
      secondary outcomes [deficiency ratio=d/(b+d)] were analyzed. The deficiency ratio
      describes the thinning of the remaining myometrium (d=residual myometrial
      thickness) over the "apparent" defect (b=scar depth). Results In total, 124 of
      the 156 recruited women were examined, eight were excluded from analysis. The
      double scarring rate decreased from 42.9% (12/28) in CS2-G to 7.1% (2/28) in the
      Int-G [difference: 35.8%; 95% confidence interval (CI) (13.2, 54.5); P=0.002].
      Two-way analysis of variance (ANOVA) revealed a significant difference between
      CS2-G and the Int-G in the deficiency ratio adjusted for elective/primary
      cesareans, with thicker remaining myometrium over the scar defect in the Int-G
      [difference: -0.24; 95% CI (-0.34, -0.15); P<0.001]. Conclusion Ultrasound-guided
      resection of the uterine scar area during repeat cesareans reduces the scarring
      rate and improves thickness of the remaining myometrium as detected by
      ultrasonography 6-9 months postoperatively.

PMID- 29570455
TI  - Computerized prediction system for the route of delivery (vaginal birth versus
      cesarean section).
AB  - Aim To develop a supportive computerized prediction system for the route of
      delivery. Materials and methods This study consisted of 2127, 3548 and 1723
      deliveries for the years 1976, 1986 and 1996, respectively. We have developed a
      supervised artificial neural network (ANN) for predicting the delivery route. We
      have used a back-propagation learning algorithm for this purpose. The data used
      for the computerized system were obtained during the admission of the patients to
      the delivery room at the beginning of the first stage of labor after pelvic
      examination and examination/evaluation of the mother and fetus. The input
      variables for the ANN were maternal age, gravida, parity, gestational age at
      birth, necessity and type of labor induction, presentation of the baby at birth,
      and maternal disorders and/or risk factors. The outputs of the algorithm were
      vaginal delivery or cesarean section (CS). Results The CS rates in 1976, 1986 and
      1996 were 9.1%, 18.5% and 44.5%, respectively. We have demonstrated that the
      system's specificity and sensitivity were 97.5% and 60.9%, respectively. The
      false positive rate was 2.5%, whereas the false negative rate was 39.1%. The
      positive and negative predictive values were 81.8% and 93.1%, respectively.
      Conclusion Our computerized system, heretofore named as the "Adana System," can
      be used as a supportive decision-making system for predicting the delivery route.
      The Adana System might be a useful tool to protect physicians against adverse
      medicolegal issues.

PMID- 29570456
TI  - Computer-aided diagnosis of prostate cancer using multi-parametric MRI:
      comparison between PUN and Tofts models.
AB  - Computer-aided diagnosis (CAD) systems are increasingly being used in clinical
      settings to report multi-parametric magnetic resonance imaging (mp-MRI) of the
      prostate. Usually, CAD systems automatically highlight cancer-suspicious regions
      to the radiologist, reducing reader variability and interpretation errors.
      Nevertheless, implementing this software requires the selection of which mp-MRI
      parameters can best discriminate between malignant and non-malignant regions. To
      exploit functional information, some parameters are derived from dynamic contrast
      enhanced (DCE) acquisitions. In particular, much CAD software employs
      pharmacokinetic features, such as K trans and k ep, derived from the Tofts model,
      to estimate a likelihood map of malignancy. However, non-pharmacokinetic models
      can be also used to describe DCE-MRI curves, without any requirement for prior
      knowledge or measurement of the arterial input function, which could potentially
      lead to large errors in parameter estimation. In this work, we implemented an
      empirical function derived from the phenomenological universalities (PUN) class
      to fit DCE-MRI. The parameters of the PUN model are used in combination with T2
      weighted and diffusion-weighted acquisitions to feed a support vector machine
      classifier to produce a voxel-wise malignancy likelihood map of the prostate. The
      results were all compared to those for a CAD system based on Tofts
      pharmacokinetic features to describe DCE-MRI curves, using different quality
      aspects of image segmentation, while also evaluating the number and size of false
      positive (FP) candidate regions. This study included 61 patients with 70 biopsy
      proven prostate cancers (PCa). The metrics used to evaluate segmentation quality
      between the two CAD systems were not statistically different, although the PUN
      based CAD reported a lower number of FP, with reduced size compared to the Tofts
      based CAD. In conclusion, the CAD software based on PUN parameters is a feasible
      means with which to detect PCa, without affecting segmentation quality, and hence
      it could be successfully applied in clinical settings, improving the automated
      diagnosis process and reducing computational complexity.

PMID- 29570457
TI  - A scalable and deformable stylized model of the adult human eye for radiation
      dose assessment.
AB  - With recent changes in the recommended annual limit on eye lens exposures to
      ionizing radiation, there is considerable interest in predictive computational
      dosimetry models of the human eye and its various ocular structures including the
      crystalline lens, ciliary body, cornea, retina, optic nerve, and central retinal
      artery. Computational eye models to date have been constructed as stylized
      models, high-resolution voxel models, and polygon mesh models. Their common
      feature, however, is that they are typically constructed of nominal size and of a
      roughly spherical shape associated with the emmetropic eye. In this study, we
      present a geometric eye model that is both scalable (allowing for changes in eye
      size) and deformable (allowing for changes in eye shape), and that is suitable
      for use in radiation transport studies of ocular exposures and radiation
      treatments of eye disease. The model allows continuous and variable changes in
      eye size (axial lengths from 20 to 26 mm) and eye shape (diopters from  -12 to 
      +6). As an explanatory example of its use, five models (emmetropic eyes of small,
      average, and large size, as well as average size eyes of  -12D and  +6D) were
      constructed and subjected to normally incident beams of monoenergetic electrons
      and photons, with resultant energy-dependent dose coefficients presented for both
      anterior and posterior eye structures. Electron dose coefficients were found to
      vary with changes to both eye size and shape for the posterior eye structures,
      while their values for the crystalline lens were found to be sensitive to changes
      in only eye size. No dependence upon eye size or eye shape was found for photon
      dose coefficients at energies below 2 MeV. Future applications of the model can
      include more extensive tabulations of dose coefficients to all ocular structures
      (not only the lens) as a function of eye size and shape, as well as the
      assessment of x-ray therapies for ocular disease for patients with non-emmetropic
      eyes.

PMID- 29570458
TI  - 3D printing strategies for peripheral nerve regeneration.
AB  - After many decades of biomaterials research for peripheral nerve regeneration, a
      clinical product (the nerve guide), is emerging as a proven alternative for
      relatively short injury gaps. This review identifies aspects where 3D printing
      can assist in improving long-distance nerve guide regeneration strategies. These
      include (1) 3D printing of the customizable nerve guides, (2) fabrication of
      scaffolds that fill nerve guides, (3) 3D bioprinting of cells within a
      matrix/bioink into the nerve guide lumen and the (4) establishment of growth
      factor gradients along the length a nerve guide. The improving resolution of 3D
      printing technologies will be an important factor for peripheral nerve
      regeneration, as fascicular-like guiding structures provide one path to improved
      nerve guidance. The capability of 3D printing to manufacture complex structures
      from patient data based on existing medical imaging technologies is an exciting
      aspect that could eventually be applied to treating peripheral nerve injury.
      Ultimately, the goal of 3D printing in peripheral nerve regeneration is the
      automated fabrication, potentially customized for the patient, of structures
      within the nerve guide that significantly outperform the nerve autograft over
      large gap injuries.

PMID- 29570459
TI  - On hiring an associate.

PMID- 29570460
TI  - Finding a successful associate to fit your office.

PMID- 29570462
TI  - A capital convention.

PMID- 29570461
TI  - The PowerScope system for simplified Class II treatment.

PMID- 29570463
TI  - Correction of severe unilateral scissor bite in growing Class II patients.

PMID- 29570464
TI  - Nonsurgical management of severe reverse overbite in a young adult.

PMID- 29570465
TI  - Helping patients properly connect elastic bands.

PMID- 29570466
TI  - Ultrasonographic Imaging of the Median Nerve With a Struthers Ligament.

PMID- 29570467
TI  - Efficacy of Bedside Respiratory Muscle Training in Patients With Stroke: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: Inspiratory and expiratory muscles are important for effective
      respiratory function. This study aimed to investigate the efficacy of bedside
      respiratory muscle training on pulmonary function and stroke-related disabilities
      in stroke rehabilitation. DESIGN: Patients with stroke (N = 40) in a
      rehabilitation unit were randomly assigned to either the intervention group (n1 =
      20) or the control group (n2 = 20). Both groups participated in a conventional
      stroke rehabilitation program. During the study period, the intervention group
      received bedside respiratory muscle training twice a day for 3 wks. The
      respiratory muscle training consisted of (1) a breath stacking exercise, (2)
      inspiratory muscle training, and (3) expiratory muscle training. The primary
      outcomes were measures of pulmonary function: forced vital capacity, forced
      expiratory volume in 1 sec, and peak flow. Secondary outcomes were stroke-related
      disabilities assessed using the National Institutes of Health Stroke Scale,
      Modified Barthel Index, Berg Balance Scale, Fugl-Meyer Assessment, the Korean
      Mini-Mental State Examination, and pneumonia incidence. RESULTS: Pulmonary
      function was significantly improved in the intervention group after 3 wks of
      respiratory muscle training (P < 0.05). This improvement in pulmonary function
      was independent of the improvement in stroke-related disabilities. CONCLUSION:
      Three weeks of respiratory muscle training had significant effects on pulmonary
      function in stroke survivors. TO CLAIM CME CREDITS: Complete the self-assessment
      activity and evaluation online at http://www.physiatry.org/JournalCME CME
      OBJECTIVES: Upon completion of this article, the reader should be able to: (1)
      Appreciate the respiratory function changes that occur in patients following a
      stroke; (2) Describe appropriate inspiratory and expiratory muscle training
      techniques to improve pulmonary function in patients following a stroke; (3)
      Enhance ability to implement inpatient; and (4) Determine appropriate respiratory
      training programs for patients following stroke. LEVEL: Advanced ACCREDITATION:
      The Association of Academic Physiatrists is accredited by the Accreditation
      Council for Continuing Medical Education to provide continuing medical education
      for physicians.The Association of Academic Physiatrists designates this Journal
      based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM.
      Physicians should only claim credit commensurate with the extent of their
      participation in the activity.

PMID- 29570468
TI  - Novel oral anticoagulants in chronic kidney disease: ready for prime time?
AB  - PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are at increased
      risk of atrial fibrillation, stroke, and bleeding posing unique clinical
      challenges. Novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban,
      and apixaban have become recognized as alternative therapy to Vitamin K
      Antagonists (VKA) regarding the prevention of venous thromboembolism (VTE) and
      reduce the risk of stroke in atrial fibrillation. However, the understanding of
      NOACs in CKD is still underdeveloped. This review summarizes recent literature on
      the efficacy and safety of NOACs in patients with CKD. RECENT FINDINGS: Studies
      focusing on patients with moderate kidney disease were drawn from post hoc
      analyses from three major NOAC trials, meta-analyses, and postmarketing
      surveillance studies. Cumulatively, these studies continue to demonstrate NOACs
      as equivalent if not superior therapies to VKAs in regards to both efficacy and
      safety. These studies are limited by small sample sizes as well as a lack of
      direct comparison between NOACs. SUMMARY: The role of NOACs in managing VTE and
      atrial fibrillation is increasing. Current research suggests that NOACs are at
      least as efficacious and well tolerated as VKAs. More research is required to
      elucidate which NOAC is preferable in the clinical setting.

PMID- 29570469
TI  - Door-to-balloon time and cardiac mortality in acute myocardial infarction by
      total occlusion of the left circumflex artery.
AB  - BACKGROUND: Acute myocardial infarction (AMI) caused by total occlusion of the
      left circumflex artery (LCX) can present as non-ST-segment elevation myocardial
      infarction (NSTEMI). We evaluate whether door-to-balloon time (DBT) is associated
      with cardiac mortality in patients with total occlusion of the LCX. PATIENTS AND
      METHODS: From the Korea Acute Myocardial Infarction Registry, patients with AMI
      who had total occlusion with a Thrombolysis In Myocardial Infarction flow grade
      of 0 were included. We determined the factors for delay in primary percutaneous
      coronary intervention (DBT>90 min) and evaluated cardiac mortality for a median
      period of 14 months. RESULTS: Mean DBT was 68 min (interquartile range=50-156
      min), and the achievement rate of DBT less than or equal to 90 min was 66.9% in
      the entire study population. More than half of patients with total occlusion of
      LCX were presented as NSTEMI (57.7%). Among patients with total occlusion of the
      LCX, the mean DBT was 136 min (interquartile range=60-484 min), and the
      achievement rate of DBT less than or equal to 90 min was 42.8%. On multivariate
      analysis, LCX occlusion was an important factor for DBT more than 90 min (odds
      ratio: 1.766, P<0.001). Among patients with LCX occlusion, cardiac mortality was
      higher in patients with ST-segment elevation (6.2 vs. 11.0%, P=0.024).
      CONCLUSION: This study showed that LCX occlusion was a significant factor for the
      delay in primary percutaneous coronary intervention on account of presenting as
      NSTEMI. Cardiac mortality was not associated with DBT more than 90 min but with
      ST-segment elevation in AMI patients with total occlusion of the LCX.

PMID- 29570470
TI  - The marketing of testosterone treatments for age-related low testosterone or 'Low
      T'.
AB  - PURPOSE OF REVIEW: To summarize the research evidence on promotion of
      testosterone for 'Low T', or age-related hypogonadism. RECENT FINDINGS: Marketing
      of testosterone for 'Low T' has relied on strategies that are inadequately
      regulated to prevent off-label promotion, such as unbranded 'disease-awareness'
      advertising campaigns targeting the general public, sponsored continuing medical
      education (CME) and ghostwriting. A recent US analysis of television advertising
      exposure levels versus insurance claims found that both unbranded 'disease
      awareness' advertising and branded ads were associated with increased rates of
      testosterone testing, treatment initiation, and treatment without prior testing.
      Exposes of sponsored CME and ghostwriting indicate misrepresentation of the
      research evidence on the sequelae of untreated low testosterone and on treatment
      efficacy. In the United States, advertising to the general public ceased in 2014
      after the Food and Drug Administration changed product labeling to clarify that
      testosterone is only indicated for pathological hypogonadism. Unbranded 'disease
      awareness' advertising to the general public and 'Low T' messages for health
      professionals have continued elsewhere. SUMMARY: The review of the experience of
      promotion of testosterone for 'Low T' and research evidence on effects of
      advertising targeting the public highlights the need for improved regulation of
      unbranded 'disease awareness' advertising to ensure adequate protection of
      public.

PMID- 29570471
TI  - Retention and adherence: global challenges for the long-term care of adolescents
      and young adults living with HIV.
AB  - PURPOSE OF REVIEW: Adolescents living with HIV are the only age group with
      increasing HIV mortality at a time of global scale-up of access to antiretroviral
      therapy (ART). As a 'treat all' strategy is implemented worldwide, it is
      critically important to optimize retention and adherence for this vulnerable
      group. RECENT FINDINGS: Adolescents and young adults living with HIV have poorer
      outcomes when compared with adults at each stage of the HIV care cascade,
      irrespective of income setting. Rates of viral suppression are lowest for
      adolescents living with HIV, and adherence to ART remains an enormous challenge.
      High-quality studies of interventions to improve linkage to, and retention in,
      care on suppressive ART are starkly lacking for adolescents and young adults
      living with HIV across the globe. However, examples of good practice are
      beginning to emerge but require large-scale implementation studies with outcome
      data disaggregated by age, route of infection, and income setting, and include
      young pregnant women and key populations groups. SUMMARY: There is an urgent need
      for evidence-based interventions addressing gaps in the adolescent HIV care
      cascade, including supporting retention in care and adherence to ART.

PMID- 29570472
TI  - Report of Clinic Unresponsive Chemotherapy-Associated Hepatitis B Reactivation
      and Hepatitis in Lung Cancer.

PMID- 29570473
TI  - Graphical Diagnosis of Confounding Bias in Instrumental Variable Analysis.

PMID- 29570474
TI  - Validation of Severe Maternal Morbidity on the US Certificate of Live Birth.

PMID- 29570475
TI  - Tocilizumab in Giant Cell Arteritis.
AB  - Giant cell arteritis is a granulomatous immune-mediated vasculitis of medium and
      large vessels. It most commonly affects white females over the age of 50 and is
      the most common primary vasculitis in the United States. Treatment of this
      disease has classically been with high-dose corticosteroids, but this therapy has
      been associated with severe morbidity and mortality. Tocilizumab, a humanized
      monoclonal antibody targeting the interleukin-6 receptor, has been used with
      great efficacy and safety in rheumatoid arthritis and systemic-onset juvenile
      idiopathic arthritis. As interleukin-6 has been shown to be a key cytokine in
      giant cell arteritis, the use of an inhibiting agent has been explored. In the 15
      case reports/series that were reviewed, most patients were given tocilizumab due
      to refractory giant cell arteritis and/or intolerance to glucocorticoid therapy,
      and most experienced remission of symptoms. At this time, there are only 2
      randomized control trials to evaluate the efficacy and safety of tocilizumab use
      in giant cell arteritis. The phase II trial by Villiger et al and the GiACTA
      trial both showed that tocilizumab greatly increased the rate of sustained
      remission in giant cell arteritis over the course of 1 year. The most common
      adverse events were similar to those seen with use in rheumatoid arthritis:
      infections, neutropenia, and increases in lipids and liver function test enzymes.
      Based on the results of numerous case studies and the 2 randomized control
      trials, tocilizumab is the first agent to be approved by the Food and Drug
      Administration for treatment of giant cell arteritis.

PMID- 29570476
TI  - Patent Foramen Ovale and Hypoxemia.
AB  - Patent foramen ovale (PFO), an embryonic remnant of the fetal circulation, is
      present in 20-25% of adults. Although recent observational studies and clinical
      trials have established the link between PFO-mediated right-to-left shunting with
      cryptogenic stroke and migraine with aura, the role of a PFO in exacerbating
      hypoxemic medical conditions (ie, sleep apnea, chronic obstructive pulmonary
      disease, pulmonary hypertension, platypnea-orthodeoxia, pulmonary arteriovenous
      malformation, high-altitude pulmonary edema, and exercise desaturation) remains
      less understood. PFO-mediated hypoxemia occurs when deoxygenated venous blood
      from the right atrium enters and mixes with oxygenated arterial blood in the left
      atrium. Patients with an intracardiac right-to-left shunt may have profound
      hypoxemia out of proportion to underlying primary lung disease, even in the
      presence of normal right-sided pressures. The presence of right-to-left cardiac
      shunting can exacerbate the degree of hypoxemia in patients with underlying
      pulmonary disorders. In a subset of these patients, percutaneous PFO closure may
      result in marked improvement in dyspnea and hypoxemia. This review discusses the
      association between PFO-mediated right-to-left shunting with medical conditions
      associated with hypoxemia and explores the role of percutaneous PFO closure in
      alleviating the hypoxemia.

PMID- 29570478
TI  - Serum Exoglycosidases in Children and Adolescents With Harmful Alcohol Use.
AB  - OBJECTIVE: There is a lack of accurate alcohol-use biomarkers in
      children/adolescents due to a short drinking duration/rapid normalization of
      elevated markers. We checked if lysosomal exoglycosidases, elevated earlier in
      binge-drinking young adults, can be applicable in children/adolescents as markers
      of harmful alcohol use. METHODS: The serum activities (pKat/mL) of alpha
      fucosidase (FUC), beta-galactosidase (GAL), beta-glucuronidase (GLU), beta
      hexosaminidase (HEX; its HEX A and HEX B isoenzymes), and alpha-mannosidase (MAN)
      were determined in 20 healthy controls (C) and 25 children/adolescents with
      harmful alcohol use (intoxicated by alcohol at hospital admission -AI1 and on the
      next day -AI2). RESULTS: The serum HEX A and alanine aminotransferase (ALT)
      activity was significantly higher in the AI1 group than in the control. The
      activities of FUC, GAL, GLU, HEX B, and MAN were lower in the AI group. We found
      fair and poor accuracy, respectively, for increased enzymes HEX A and ALT. We
      found fair accuracy for decreased HEX B (AI1) and MAN (AI1), good accuracy for
      GLU (AI2), FUC (AI2), GAL (AI1, AI2), MAN (AI2), and excellent for FUC (AI1).
      Correlations were found: ALT with C-reactive protein (CRP), HEX A with white
      blood cell (WBC) count, blood alcohol concentration with FUC, MAN and HEX B, and
      WBC with FUC. CONCLUSIONS: Decreased FUC, GLU, GAL, MAN values, and especially
      FUC (AI1) have the potential to be markers of harmful alcohol use in
      children/adolescents. The raised activity of HEX A and ALT points to the need for
      further research to check another inflammatory agent as potential alcohol marker
      in children and adolescents. Samples need to be collected before intravenous
      fluid therapy.

PMID- 29570477
TI  - Is Preconception Substance Use Associated With Unplanned or Poorly Timed
      Pregnancy?
AB  - OBJECTIVE: Unplanned and poorly timed pregnancies are associated with adverse
      maternal and neonatal outcomes. Further understanding of preconception substance
      use with unplanned and poorly timed pregnancy is warranted. METHODS: Data were
      analyzed from a prospective study enrolling women early in pregnancy.
      Preconception tobacco, alcohol, marijuana, opioid, and cocaine use was
      ascertained. Participants reported whether their current pregnancy was planned
      and whether it was a good time to be pregnant. Multivariable logistic regression
      modeling generated risk estimates for preconception substance use, and pregnancy
      planning and timing, adjusting for confounders. RESULTS: Overall, 37.2% reported
      unplanned pregnancy, 13.0% poorly timed pregnancy, and 39.0% reported either
      unplanned and/or poorly timed pregnancy. Within 6 months preconception, one-fifth
      (20.2%) reported nicotine cigarette use. In the month before conception, 71.8%
      reported alcohol use, 6.5% marijuana, and approximately 1% opioid or cocaine use.
      Multivariable analysis demonstrated preconception opioid use was associated with
      increased odds of poorly timed pregnancy (odds ratio [OR] 2.87, 95% confidence
      interval [CI] 1.03-7.99). Binge drinking the month before conception was
      associated with increased odds of poorly timed pregnancy and unplanned pregnancy
      (OR 1.75, 95% CI 1.01-3.05; and OR 1.68, 95% CI 1.01-2.79, respectively).
      Marijuana use 2 to 3 times in the month preconception was associated with
      increased risk of unplanned pregnancy, and unplanned and/or poorly timed
      pregnancy compared with nonuse (OR 1.78, 95% CI 1.03-3.08; and OR 1.79, 95% CI
      1.01-3.17, respectively). Preconception tobacco or cocaine use was not associated
      with unplanned or poorly timed pregnancy following adjustment. CONCLUSIONS: We
      demonstrate increased odds of unplanned or poorly timed pregnancy among women
      with preconception binge drinking, marijuana use, and opioid use; however, no
      association is observed with other substances after multivariable adjustment,
      including tobacco. Further research to evaluate high-level preconception
      substance use and substance disorders with pregnancy planning and timing is
      warranted. Focused efforts optimizing preconception health behaviors and reducing
      risk of unplanned or poorly timed pregnancy are needed.

PMID- 29570479
TI  - Effects of arm elevation on radial artery pressure: a new method to distinguish
      hypovolemic shock and septic shock from hypotension.
AB  - OBJECTIVES: In this prospective observational study, we investigated the
      variability in radial artery invasive blood pressure associated with arm
      elevation in patients with different hemodynamic types. PATIENTS AND METHODS: We
      carried out a prospective observational study using data from 73 general
      anesthesia hepatobiliary postoperative adult patients admitted to an ICU over a 1
      year period. A standard procedure was used for the arm elevation test. The value
      of invasive radial arterial pressure was recorded at baseline, and 30 and 60 s
      after the arm had been raised from 0 degrees  to 90 degrees . We compared the
      blood pressure before versus after arm elevation, and between hemodynamically
      stable, hypovolemic shock, and septic shock patient groups. RESULTS: In all 73
      patients, systolic arterial pressure (SAP) decreased, diastolic arterial pressure
      (DAP) increased, and pulse pressure (PP) decreased at 30 and 60 s after arm
      elevation (P<0.01), but the mean arterial pressure (MAP) was unchanged (P>0.05).
      On comparing 30 and 60 s, there was no significant difference in SAP, DAP, PP, or
      MAP (P>0.05). In 40 hemodynamically stable patients, SAP and PP decreased, and
      DAP and MAP increased significantly at 30 and 60 s after arm elevation compared
      with baseline (P<0.01). In 16 hypovolemic patients, SAP, DAP, and MAP increased
      significantly compared with baseline at 30 and 60 s (P<0.01), but PP was
      unchanged (P>0.05). In 17 patients with septic shock, SAP, PP, and MAP decreased
      significantly versus baseline at 30 and 60 s (P<0.01), but DAP was unchanged
      (P>0.05). Comparison of the absolute value of pressure change of septic shock
      patients at 30 s after raising the arm showed that SAP, DAP, and MAP changes were
      significantly lower compared with those in hypovolemic shock and hemodynamically
      stable patients (P<0.01). The areas under the receiver operator characteristic
      curve for predicting septic shock was 0.930 [95% confidence interval (CI): 0.867
      0.992, P< 0.001] for change value at 30 s after arm elevation of SAP. The best
      cut-off point for the SAP change value was -5 mmHg or less, with a sensitivity of
      94.12%, a specificity of 80.36%, a positive likelihood ratio of 4.79 (95% CI: 2.8
      8.2), and a negative likelihood ratio of 0.073 (95% CI: 0.01-0.5). CONCLUSION:
      Our study shows that hypovolemic shock and septic shock patients have
      significantly different radial artery invasive blood pressure changes in an arm
      elevation test, which could be applied as a new method to distinguish hypovolemic
      shock and septic shock from hypotension.

PMID- 29570480
TI  - Evaluation of D-dimer levels in patients with prosthetic valve thrombosis:
      relationship with thrombus burden and cerebrovascular events.
AB  - : Plasma D-dimer level is an indicator of thrombosis and endogenous fibrinolytic
      activity. We investigated the association between the D-dimer levels and thrombus
      burden and cerebrovascular events in patients with obstructive prosthetic valve
      thrombosis (PVT). This retrospective study included 47 patients with obstructive
      left-sided PVT and 32 controls in whom PVT was excluded with comprehensive
      transthoracic and transesophageal echocardiography (TEE). The patient group
      included 11 aortic, 27 mitral, and 9 aortic and mitral valve PVT patients and the
      control group included 2 aortic, 25 mitral, and 5 aortic and mitral valve
      patients. Laboratory analysis including plasma D-dimer levels was performed at
      the time of admission in all patients. The baseline characteristics were similar
      between the two groups. The plasma D-dimer levels were significantly higher in
      patients with obstructive PVT compared with controls [680 (110-3590) vs. 310 (80
      380) MUg/l; P < 0.001]. By multivariate logistic regression analysis high D-dimer
      level, low-INR value on admission, high NYHA functional class and recent history
      of cerebrovascular accident (CVA), and transient ischemic attack (TIA) were the
      independent predictors of obstructive PVT. A plasma D-dimer level of greater than
      365 MUg/l predicted the presence of PVT with a sensitivity of 81% and a
      specificity of 69% (AUC= 0.781, P < 0.001). Plasma D-dimer levels were
      significantly higher in patients with a recent history of CVA/TIA [2140 (470
      2980) vs. 590 (380-830) MUg/l; P = 0.021]. In addition to the so-called
      indicators of PVT including subtherapeutic anticoagulation, increased D-Dimer
      levels may strengthen the suspicion of PVT. Moreover, higher plasma D-dimer
      levels were associated with higher thrombus burden and higher prevalence of
      recent CVA/TIA.

PMID- 29570481
TI  - Intraoperative blood pressure levels in young and anaesthetised children: are we
      getting any closer to the truth?
AB  - PURPOSE OF REVIEW: Blood pressure is a basic feature of monitoring during
      anaesthesia. However, it is very unclear what blood pressures are normal during
      anaesthesia in children. Furthermore, the clinical consequences of low blood
      pressure are also uncertain. Similarly, it is unclear when to initiate therapy
      for hypotension during anaesthesia. This review summarizes the most recent
      development on the interpretation of blood pressure measurements in children and
      the relation of low blood pressure to clinical outcome. RECENT FINDINGS: Recently
      published (multicentre) database studies show that alleged complications of
      intraoperative hypotension (brain ischaemia, kidney dysfunction, myocardial
      ischaemia and multiple organ dysfunction) are very rare in children after
      anaesthesia noncardiac procedures. Furthermore, other studies show that a
      considerable number of patients have blood pressure lower than a threshold
      according to the current standards treatment of Paediatric Life Support. SUMMARY:
      The recently published reference tables can guide anaesthesiologist in daily
      practice to define intraoperative hypotension. However, there are situations in
      which a higher blood pressure is recommendable and an individual approach is
      required.

PMID- 29570482
TI  - Postmortem Cholesterol Levels in Peripheral Nerve Tissue: Preliminar
      Considerations on Interindividual and Intraindividual Variation.
AB  - The study reports the evolution of the demyelinization process based on
      cholesterol ([CHOL]) levels quantified in median nerve samples and collected at
      different times-from death from both right and left wrists. The statistical data
      show that the phenomenon evolves differently in the right and left nerves. Such a
      difference can reasonably be attributed to a different multicenter evolution of
      the demyelinization. For data analysis, the enrolled subjects were grouped by
      similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48
      hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected
      within 48 hours of death allowed for a PMI estimation according to the following
      equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and
      PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this
      correlation cannot be considered to be definitive because of the limitation of
      the small size of the samples analyzed, because the differences in the sampling
      time and the interindividual and intraindividual variation may influence the
      demyelinization process.

PMID- 29570483
TI  - Sudden and Unexpected Death During Sexual Activity, Due to a Glial Cyst of the
      Pineal Gland.
AB  - Cysts of the pineal gland are benign lesions. Often asymptomatic, in the majority
      of cases they are discovered incidentally during brain magnetic resonance imaging
      or autopsy. Sporadically, however, they may cause such symptoms as chronic
      headache, loss of consciousness, corticospinal and sensory impairment, and, in
      some cases, even sudden death. A 45-year-old woman, in apparently good health,
      collapsed and died suddenly, after reaching orgasm while engaged in sexual
      intercourse. According to the circumstantial account of her relatives, the woman
      suffered from severe headaches, which were exacerbated by certain types of
      physical strain, such as sexual activity. Postmortem examination revealed no
      external injuries or internal diseases except for a cystic lesion of the pineal
      gland. Microscopically, the wall of the cyst consisted of a layer of glial tissue
      surrounded by an area of pineal elements. A complete forensic approach concluded
      that the cause of death was fatal cardiorespiratory failure resulting from
      midbrain compression due to a nonneoplastic pineal gland cyst, exacerbated by
      sexual activity. In this case, the intracranial pressure increase, secondary to
      Valsalva maneuver during climax, may further aggravate compression on the
      brainstem, thus concurring to determine the death.

PMID- 29570484
TI  - A Forensic Approach to Sotos Syndrome.
AB  - Sotos syndrome is a childhood overgrowth condition that is caused by deletions or
      mutations in the NSD1 gene located on chromosome 5q35. The syndrome is associated
      with a wide variety of features that may result in sudden death. The aim of this
      report was to investigate the spectrum of potential findings in cases presenting
      to autopsy. A 4-month-old girl with Sotos syndrome was found dead after being put
      down to sleep. Her death was due to complex cardiac disease that included
      surgically repaired atrial and ventricular septal defects and valve
      abnormalities, with cardiomegaly. If the features of Sotos syndrome are
      identified de novo at autopsy, genetic investigations are warranted, although the
      recurrence risk is low. The involvement of a clinical geneticist may assist in
      evaluating cases, and postmortem imaging studies may provide useful information.

PMID- 29570485
TI  - Linking Psychological Strain and Suicide Ideation: A Test of the Mediating Effect
      of Self-Determination Among Chinese Workers.
AB  - Psychosocial causes of suicidal ideation among those who do not have diagnosable
      mental illnesses remain largely unexplored. Synthesizing the strain theory of
      suicide and self-determination theory, this research tested a multiple mediator
      model linking psychological strain with suicidal ideation via three basic
      psychological need satisfaction. Data from 750 professional employees in China
      support for the partially mediated effects of psychological strain via need
      satisfaction of competence and relatedness. These findings contribute to
      understanding Chinese employees' suicidal ideation from positive psychology
      perspective that is distinct from what is known from psychopathology.

PMID- 29570486
TI  - Chronic Fibrosing Vasculitis in the Setting of Still Disease.

PMID- 29570487
TI  - Positive Patch Test to Metals in a Patient With Symmetrical Intertriginous Skin
      Eruptions: Systemic Contact Dermatitis or Lichen Planus Pigmentosus Inversus?

PMID- 29570488
TI  - Lymphomatoid Contact Dermatitis Induced by Acrylates Mimicking Lymphomatoid
      Papulosis.

PMID- 29570489
TI  - Risk Assessment of the Skin Sensitization Induction Potential of Kathon CG in
      Rinse-off and Leave-on Personal Care and Cosmetic Products.
AB  - BACKGROUND: Kathon CG is a commonly used cosmetic-grade preservative that
      contains active ingredients methylchloroisothiazolinone (MCI) and
      methylisothiazolinone (MI). OBJECTIVE: The aim of the study was to perform a skin
      sensitization induction risk assessment of daily exposure to Kathon CG after use
      of various personal care and cosmetic products. METHODS: We calculated an
      estimated daily consumer exposure level for rinse-off and leave-on products using
      the amount of product applied per application, number of applications per day, a
      retention factor, the MCI/MI concentration, and body surface area values. We
      assumed that the products contained the maximum recommended safe concentration of
      MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We
      compared estimated consumer exposure levels with the no expected sensitization
      induction level for MCI/MI and applied sensitization assessment factors to
      calculate product-specific margins of safety (MOSs). CONCLUSIONS: The MOSs for
      rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products
      ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave
      on products containing the maximum recommended safe concentration of Kathon CG
      may increase the risk of sensitization induction due to exposure to MCI/MI. In
      contrast, rinse-off products were not associated with a potential increased risk
      of skin sensitization induction.

PMID- 29570490
TI  - Patch Testing in a Patient on Dupilumab.

PMID- 29570491
TI  - Characteristics and outcome for heart failure patients with mid-range ejection
      fraction.
AB  - AIMS: The aim of this study was to compare precipitants, presenting symptoms and
      outcomes of patients with heart failure and mid-range ejection fraction (HFmrEF),
      heart failure and preserved ejection fraction (HFpEF) and heart failure with
      reduced ejection fraction (HFrEF) in an Australian cohort. METHODS: We divided
      5236 patients in the Management of Cardiac Failure program in Northern Sydney
      Australia, into HFmrEF (n = 780, 14.9%), HFpEF (n = 1956, 37.4%) and HFrEF (n =
      2500, 47.8%), using a cutoff left ventricular ejection fraction of 40-49, at
      least 50 and less than 40%, respectively. RESULTS: For most characteristics, the
      HFmrEF patients were intermediate. Hypertension among the HFrEF, HFmrEF and HFpEF
      groups was present in 50.6, 61.7 and 68.9%, respectively; age more than 85 years
      was present in 35.1, 37.6 and 42.2%; atrial fibrillation in 35.3, 44.2 and 49.9%;
      and elevated serum creatinine (>100 MUmol/l) in 59.2, 55.6 and 51.0%. For
      ischemic heart disease and ischemia as a precipitant of admission, HFmrEF
      patients were similar to the HFrEF group, and more common than in HFpEF.
      Mortality rates were not significantly different between the three groups.
      Readmission rates were highest for HFpEF (40.2%), followed by HFmrEF (42.4%) and
      HFrEF (45.4%), largely due to differences in nonheart failure readmission.
      CONCLUSION: Clinically, HFmrEF represents an intermediate phenotype, with the
      exception of resembling HFrEF with a higher incidence of ischemic heart disease.

PMID- 29570492
TI  - When do coinfections matter?
AB  - PURPOSE OF REVIEW: Advances in diagnostic methods mean that coinfections are
      increasingly being detected in clinical practice, yet their significance is not
      always obvious. In parallel, basic science studies are increasingly investigating
      interactions between pathogens to try to explain real-life observations and
      elucidate biological mechanisms. RECENT FINDINGS: Coinfections may be
      insignificant, detrimental, or even beneficial, and these outcomes can occur
      through multiple levels of interactions which include modulation of the host
      response, altering the performance of diagnostic tests, and drug-drug
      interactions during treatment. The harmful effects of chronic coinfections such
      as tuberculosis or Hepatitis B and C in association with HIV are well
      established, and recent studies have focussed on strategies to mitigate these
      effects. However, consequences of many acute coinfections are much less certain,
      and recent conflicting findings simply highlight many of the challenges of
      studying naturally acquired infections in humans. SUMMARY: Tackling these
      challenges, using animal models, or careful prospective studies in humans may
      prove to be worthwhile. There are already tantalizing examples where
      identification and treatment of relevant coinfections seems to hold promise for
      improved health outcomes.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- 29570493
TI  - Does anthrax antitoxin therapy have a role in the treatment of inhalational
      anthrax?
AB  - PURPOSE OF REVIEW: Inhalational anthrax is a rare disease and Bacillus anthracis
      is a likely pathogen to be used in a biological attack. The lack of clinical
      experience with anthrax has led experts to develop treatment guidelines. These
      guidelines recommend anthrax antitoxin to be used in conjunction with antibiotics
      for the treatment of patients with systemic anthrax infection, yet there is still
      a lack of human or animal data to support this recommendation. RECENT FINDINGS:
      The U.S. Food and Drug Administration-approved anthrax antitoxins in 2012, 2015,
      and 2016. These products have been stockpiled for use in a public health
      emergency. Although efficacy is high when given early, their efficacy diminishes
      quickly when given after the development of bacteremia. Animal studies showing a
      significant incremental benefit of antitoxin therapy when combined with
      antibiotic therapy were not required by the U.S. Food and Drug Administration for
      product approval. SUMMARY: There is no conclusive evidence demonstrating that
      anthrax antitoxin therapy, when combined with a therapeutic course of antibiotics
      provides a survival benefit in inhalational anthrax. Additional research is
      needed in improved anthrax-antitoxin therapies, novel small molecule toxin
      inhibitors that act intracellularly, and studies of supportive care such as
      hemodynamic and ventilatory support, to improve the survival for inhalational
      anthrax patients and help mitigate the threat caused by the misuse of B.
      anthracis.

PMID- 29570494
TI  - The impact of paediatric antimicrobial stewardship programmes on patient
      outcomes.
AB  - PURPOSE OF REVIEW: Although there has been an unprecedented global effort to
      reduce the spread of antimicrobial resistance, little emphasis has been placed on
      children. This review aims to evaluate the impact of paediatric antimicrobial
      stewardship programmes as well as providing a practical approach for effectively
      implementing them in community-based settings and in hospitals. RECENT FINDINGS:
      Although rates of serious bacterial infection are low in children, the rates of
      antimicrobial use and resistance are comparable with adults. Different strategies
      are required to implement antimicrobial stewardship in community-based settings
      compared to in hospitals. Nationally coordinated, whole-system approaches have
      achieved long-term, sustainable reductions in antimicrobial prescribing, as well
      as reductions in resistance rates at population level, with no evidence of an
      increase in rate of serious infection or bacterial complications. SUMMARY:
      Antimicrobial stewardship programmes in neonates and children have unique
      characteristics and issues. There is currently no consensus on how to measure
      consumption of antimicrobials in neonates and children. This is a research
      priority. Benchmarking and clinical networks in neonates and paediatrics are
      important to share practice and drive best use of antimicrobials.

PMID- 29570496
TI  - Taste alterations and cancer treatment.
AB  - PURPOSE OF REVIEW: In this review, we explore issues on the physiology of taste
      and smell and we critically review recent literature of taste and smell changes
      and the impact on food preferences throughout the cancer treatment trajectory.
      RECENT FINDINGS: Subjective measurements such as validated questionnaires can be
      valuable for the clinical setting and many studies describe taste and smell
      changes by self-report. Because both smell and taste are interrelated, these
      subjective results are difficult to interpret. Recent studies have looked more
      specifically at one type of malignancy with a consistent and homogeneous
      treatment with chemotherapy using objective taste assessment such as
      electrogustometry, liquid tastants or filter paper strips. SUMMARY: Taste is a
      combination of different sensations: smell, texture, temperature and saliva play
      an important role in determining the overall flavor of food. The mechanism for
      taste and smell abnormalities in cancer patients treated with systemic therapies
      remains unclear.

PMID- 29570495
TI  - The impact of malnutrition on childhood infections.
AB  - PURPOSE OF REVIEW: Almost half of all childhood deaths worldwide occur in
      children with malnutrition, predominantly in sub-Saharan Africa and South Asia.
      This review summarizes the mechanisms by which malnutrition and serious
      infections interact with each other and with children's environments. RECENT
      FINDINGS: It has become clear that whilst malnutrition results in increased
      incidence, severity and case fatality of common infections, risks continue beyond
      acute episodes resulting in significant postdischarge mortality. A well
      established concept of a 'vicious-cycle' between nutrition and infection has now
      evolving to encompass dysbiosis and pathogen colonization as precursors to
      infection; enteric dysfunction constituting malabsorption, dysregulation of
      nutrients and metabolism, inflammation and bacterial translocation. All of these
      interact with a child's diet and environment. Published trials aiming to break
      this cycle using antimicrobial prophylaxis or water, sanitation and hygiene
      interventions have not demonstrated public health benefit so far. SUMMARY: As
      further trials are planned, key gaps in knowledge can be filled by applying new
      tools to re-examine old questions relating to immune competence during and after
      infection events and changes in nutritional status; and how to characterize overt
      and subclinical infection, intestinal permeability to bacteria and the role of
      antimicrobial resistance using specific biomarkers.

PMID- 29570497
TI  - Radiation Exposure and Health Risks for Orthopaedic Surgeons.
AB  - Orthopaedic surgeons are routinely exposed to intraoperative radiation and,
      therefore, follow the principle of "as low as reasonably achievable" with regard
      to occupational safety. However, standardized education on the long-term health
      effects of radiation and the basis for current radiation exposure limits is
      limited in the field of orthopaedics. Much of orthopaedic surgeons' understanding
      of radiation exposure limits is extrapolated from studies of survivors of the
      atomic bombings in Hiroshima and Nagasaki, Japan. Epidemiologic studies on cancer
      risk in surgeons and interventional proceduralists and dosimetry studies on true
      radiation exposure during trauma and spine surgery recently have been conducted.
      Orthopaedic surgeons should understand the basics and basis of radiation exposure
      limits, be familiar with the current literature on the incidence of solid tumors
      and cataracts in orthopaedic surgeons, and understand the evidence behind current
      intraoperative fluoroscopy safety recommendations.

PMID- 29570498
TI  - Routine Plain Radiographs in the Setting of Atraumatic Shoulder Pain: Are They
      Useful?
AB  - INTRODUCTION: Plain radiographs of the shoulder are routinely obtained for
      patients presenting with atraumatic shoulder pain. The diagnostic utility of
      these radiographs is debatable. METHODS: Patients presenting for the first time
      to a shoulder clinic with atraumatic shoulder pain received a plain radiographic
      series. After considering their medical history and physical examination, we made
      a preliminary diagnosis and formulated a tentative treatment plan. We then
      reviewed the radiographs and determined whether the addition of these radiographs
      altered the diagnosis and/or treatment. RESULTS: A total of 343 patients met the
      inclusion criteria. Age >50 years (odds ratio, 3.3; 95% confidence interval, 1.9
      to 5.8; P < 0.00001) and weakness in forward elevation (odds ratio, 2.9; 95%
      confidence interval, 1.6 to 5.4; P = 0.0003) were associated with the presence of
      radiographic findings. Plain radiographs altered the proposed diagnosis in only
      14.9% (51/343) of cases. However, clinical management was changed in only 1.7% of
      cases. Plain radiographs had no effect on clinical management in 97.4% of
      patients younger than 50 years. DISCUSSION: Plain radiographs rarely alter the
      diagnosis or affect management in the setting of atraumatic shoulder pain,
      particularly in patients younger than 50 years. Patients may be exposed to
      unnecessary radiation, and the healthcare system as a whole may be burdened with
      the increased cost of this imaging modality. LEVEL OF EVIDENCE: Level II
      (diagnostic).

PMID- 29570499
TI  - Ketamine effects on mammalian target of rapamycin signaling in the mouse limbic
      system depend on functional dopamine D3 receptors.
AB  - Ketamine is a noncompetitive glutamate N-methyl-D-aspartic acid receptor
      antagonist. When acutely administered to rodents, it produces a rapid
      antidepressant effect. There is evidence that N-methyl-D-aspartic acid receptor
      blockade enhances glutamatergic transmission preferentially engaging alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leading to mTOR (mammalian
      target of rapamycin) pathways activation, thus resulting into downstream
      neuroadaptive changes in limbic structures. Recent in-vitro data on primary
      neuronal cultures showed that ketamine activates mTOR also in dopaminergic
      neurons, and this activation depends on the presence of functional dopamine D3
      receptors. The aim of this work was to study the in-vivo relevance of viable D3
      receptors in mediating the effects of acute ketamine administration on the mTOR
      downstream substrate p70 ribosomal S6 kinase (p70S6K), an obligatory substrate
      for mTOR. We compared the effects of single ketamine 5 mg/kg, 10 mg/kg, or
      vehicle injection in wild-type and D3 receptor knockout mice. Animals were killed
      after 60 min, and their brains were processed for p-p70S6K immunohistochemistry.
      Ketamine increased p70S6K phosphorylation in prefrontal cortex, nucleus accumbens
      core and shell, ventral tegmental area, substantia nigra, hippocampal CA1, CA2,
      and CA3, and basolateral amygdala of wild-type mice but not in mutant mice. Our
      study demonstrates that ketamine-induced p70S6K phosphorylation is dependent on
      viable D3R expressed in most of limbic structures.

PMID- 29570501
TI  - Local Anesthetic Injection Speed and Common Peroneal Nerve Block Duration: A
      Randomized Controlled Trial in Healthy Volunteers.
AB  - BACKGROUND AND OBJECTIVES: The speed of local anesthetic (LA) injections in
      peripheral regional anesthesia ranges from slow continuous infusions (3-12 mL/h)
      to rapid manual injections (>7500 mL/h). Optimizing injection speed could augment
      the spread of LA toward the targeted nerves and influence nerve block
      characteristics. The objective of this study was to investigate whether injection
      speed of a single dose of LA affects peripheral nerve block duration. METHODS:
      After approval from the Danish Regional Scientific Ethics Committee, we enrolled
      60 healthy adult volunteers. We used an ultrasound-guided catheter-based
      technique to perform a common peroneal nerve block. Participants were randomized
      to receive 4.0 mL of ropivacaine 0.2% with 1 of 5 injection speeds: 12, 60, 300,
      600, or 1800 mL/h. Investigators and participants were blinded to group
      assignment and intervention. Primary outcome was duration of sensory nerve block
      defined by insensitivity toward cold. Secondary outcomes were duration of motor
      nerve block, time to onset of sensory nerve block, and grades of sensory and
      motor nerve block.Intergroup differences were tested by one-way analysis of
      variance. RESULTS: We found no differences in sensory block duration between the
      5 groups. Durations were median [range]: 11 [6-14], 12 [9-14], 10.5 [2-15], 11 [8
      17], and 12 [9-18] hours, respectively (P = 0.294). In addition, we found no
      differences in secondary outcomes. CONCLUSIONS: Injection speed of LA in the
      range of 12 to 1800 mL/h did not affect common peroneal nerve block duration.
      CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov,
      identifier NCT02801799.

PMID- 29570500
TI  - Curcumin mitigates axonal injury and neuronal cell apoptosis through the
      PERK/Nrf2 signaling pathway following diffuse axonal injury.
AB  - Diffuse axonal injury (DAI) accounts for more than 50% of all traumatic brain
      injury. In response to the mechanical damage associated with DAI, the abnormal
      proteins produced in the neurons and axons, namely, beta-APP and p-tau, induce
      endoplasmic reticulum (ER) stress. Curcumin, a major component extracted from the
      rhizome of Curcuma longa, has shown potent anti-inflammatory, antioxidant, anti
      infection, and antitumor activity in previous studies. Moreover, curcumin is an
      activator of nuclear factor-erythroid 2-related factor 2 (Nrf2) and promotes its
      nuclear translocation. In this study, we evaluated the therapeutic potential of
      curcumin for the treatment of DAI and investigated the mechanisms underlying the
      protective effects of curcumin against neural cell death and axonal injury after
      DAI. Rats subjected to a model of DAI by head rotational acceleration were
      treated with vehicle or curcumin to evaluate the effect of curcumin on neuronal
      and axonal injury. We observed that curcumin (20 mg/kg intraperitoneal)
      administered 1 h after DAI induction alleviated the aggregation of p-tau and beta
      APP in neurons, reduced ER-stress-related cell apoptosis, and ameliorated
      neurological deficits. Further investigation showed that the protective effect of
      curcumin in DAI was mediated by the PERK/Nrf2 pathway. Curcumin promoted PERK
      phosphorylation, and then Nrf2 dissociated from Keap1 and was translocated to the
      nucleus, which activated ATF4, an important bZIP transcription factor that
      maintains intracellular homeostasis, but inhibited the CHOP, a hallmark of ER
      stress and ER-associated programmed cell death. In summary, we demonstrate for
      the first time that curcumin confers protection against abnormal proteins and
      neuronal apoptosis after DAI, that the process is mediated by strengthening of
      the unfolded protein response to overcome ER stress, and that the protective
      effect of curcumin against DAI is dependent on the activation of Nrf2.

PMID- 29570503
TI  - A Nursing Partnership to Accelerate Academic Progression.
AB  - Associate degree nursing faculty in a Midwestern state reported that their
      students were being excluded from many clinical experiences and that their
      graduates were not being hired in Magnet(r) or Magnet-seeking hospitals.
      University and community college faculty formed a partnership to promote academic
      progression. Barriers of residency requirements, financial aid, and accreditation
      were overcome. Students complete all BSN prerequisites, take ADN and BSN courses
      simultaneously, graduate with both degrees, and take the national licensure
      examination. This is a viable model allowing nursing students to remain in their
      home town, thus decreasing costs and increasing the number of BSN-prepared nurses
      in rural areas.

PMID- 29570502
TI  - Healthy People for the 21st Century: Understanding Use of Healthy People 2020 as
      a Web-Based Initiative.
AB  - OBJECTIVE: This study assesses how the nation's preeminent health promotion and
      disease prevention initiative, Healthy People, is utilized by key stakeholders.
      METHODS: A Web-based survey was administered to assess awareness and use of
      Healthy People among state, local, tribal health organizations and other key
      stakeholder groups. Follow-up interviews were conducted with a subset of
      respondents. RESULTS: Awareness and use of Healthy People have remained high
      among state, local, and tribal stakeholders. Healthy People 2020 is most
      frequently used as a data source. The Leading Health Indicators (LHIs) are an
      important element of the initiative, and nearly 90% of organizations that use the
      LHIs found them valuable. Awareness and use of other tools and resources are more
      limited. CONCLUSIONS: Healthy People continues to be a valued resource among
      public health stakeholders; however, continued outreach is needed to promote the
      use of tools and resources available on healthypeople.gov for this decade and
      beyond. Healthy People is a national initiative used most frequently as a data
      source by state and local health departments, tribal organizations, and other
      public health practitioners.

PMID- 29570505
TI  - Digestive Dilemmas.

PMID- 29570504
TI  - Effects of Cytochrome P450 (CYP) 2C19 Genotypes on Steady-State Plasma
      Concentrations of Escitalopram and its Desmethyl Metabolite in Japanese Patients
      With Depression.
AB  - BACKGROUND: Plasma concentrations of the S-enantiomer of citalopram were
      different between extensive and poor CYP2C19 metabolizers in healthy subjects and
      depressed patients. However, most studies applied dose-corrected concentrations.
      Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma
      drug concentrations in Japanese patients with depression. METHODS: Subjects in
      this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of
      escitalopram once a day. Plasma concentrations of escitalopram and
      desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were
      identified using polymerase chain reaction methods. RESULTS: There were no
      differences in the steady-state plasma concentrations of escitalopram or
      desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram)
      among CYP2C19 genotype groups. However, 1-way analysis of variance showed
      significant effects of CYP2C19 genotypes on the dose-adjusted plasma
      concentration of escitalopram but not in the dose-adjusted plasma concentration
      of desmethylescitalopram. Analysis of covariance including age, sex, and body
      weight showed significant effects of CYP2C19 genotypes on the dose-adjusted
      plasma concentration of escitalopram and the ratio of desmethylescitalopram to
      escitalopram. CONCLUSIONS: These findings suggest that the CYP2C19 variants are
      associated with steady-state plasma concentrations of escitalopram to some extent
      but are not associated with desmethylescitalopram.

PMID- 29570507
TI  - How central is central poststroke pain? The role of afferent input in poststroke
      neuropathic pain: a prospective, open-label pilot study.
AB  - Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying
      mechanisms of which are not well understood. It has been suggested that stroke
      associated loss of inhibitory neurons in the spinothalamic tract causes
      disinhibition of thalamic neurons, which autonomously generate ectopic
      nociceptive action potentials responsible for the pain experience. We
      hypothesized that CPSP is a result of misinterpretation of afferent sensory input
      by the sensitized neurons within the brain, rather than generated spontaneously
      by the damaged central nervous system (CNS) neurons. To test this hypothesis, we
      prospectively recruited 8 patients with definite CPSP affecting at least 1
      extremity. In an open-label intervention, an ultrasound-guided peripheral nerve
      block with lidocaine was performed to block afferent sensory input from a painful
      extremity. Spontaneous and evoked pain, neuropathic pain descriptors, and
      lidocaine plasma concentrations were measured. The blockade of peripheral sensory
      input resulted in complete abolition of pain in 7 of the 8 subjects within 30
      minutes (the primary outcome measure of the study), and >50% pain relief in the
      remaining participant. Median (interquartile range) spontaneous pain intensity
      changed from 6.5 (4.3-7.0) at baseline to 0 (0-0) after the block (P = 0.008).
      All mechanical/thermal hypersensitivity was abolished by the nerve block. The
      results suggest that it is unlikely that CPSP is autonomously generated within
      the CNS. Rather, this pain is dependent on afferent input from the painful region
      in the periphery, and may be mediated by misinterpretation of peripheral sensory
      input by sensitized neurons in the CNS.

PMID- 29570508
TI  - Implications of parent and child injustice appraisals for child pain and
      functional outcomes.

PMID- 29570509
TI  - Impact of obstructive sleep apnea on cardiac organ damage in patients with acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Both obstructive sleep apnea (OSA) and cardiac organ
      damage have a crucial role in acute ischemic stroke. Our aim is to explore the
      relationship between OSA and cardiac organ damage in acute stroke patients.
      METHODS: A total of 130 consecutive patients with acute ischemic stroke were
      enrolled. Patients underwent full multichannel 24-h polysomnography for
      evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index
      (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and
      posterior wall (LVPW), LV ejection fraction and left atrium enlargement.
      Information on occurrence of arterial hypertension and its treatment before
      stroke was obtained from patients' history. RESULTS: 61.9% (70) of patients,
      mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute
      stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and
      LVPW thickness and a significant left atrial enlargement as compared with
      patients without OSA. LV ejection fraction was not significantly different in
      stroke patients with and without OSA and was within normal limits. No
      relationship was found among cardiac alterations, occurrence of OSA and history
      of hypertension. CONCLUSION: Acute stroke patients with OSA had higher LV mass
      and showed greater left atrial enlargement than patients without OSA. This study
      confirms the high prevalence of OSA in stroke patients, suggesting also an
      association between OSA and cardiac target organ damage. Our finding of
      structural LV abnormalities in acute stroke patients with OSA suggests a
      potential role of OSA as contributing factor in determining both cerebrovascular
      and cardiac damage, even in absence of clear link with a history of blood
      pressure elevation.

PMID- 29570510
TI  - Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively
      antihypertensive and reduce the severity of ischemic arrhythmias in rats with
      angiotensin II-dependent hypertension.
AB  - OBJECTIVE: We examined the effects of treatment with soluble epoxide hydrolase
      inhibitor (sEHi) and epoxyeicosatrienoic acids (EETs) analogue (EET-A), given
      alone or combined, on blood pressure (BP) and ischemia/reperfusion myocardial
      injury in rats with angiotensin II (ANG II)-dependent hypertension. METHODS: Ren
      2 transgenic rats (TGR) were used as a model of ANG II-dependent hypertension and
      Hannover Sprague-Dawley rats served as controls. Rats were treated for 14 days
      with sEHi or EET-A and BP was measured by radiotelemetry. Albuminuria, cardiac
      hypertrophy and concentrations of ANG II and EETs were determined. Separate
      groups were subjected to acute myocardial ischemia/reperfusion injury and the
      infarct size and ventricular arrhythmias were determined. RESULTS: Treatment of
      TGR with sEHi and EET-A, given alone or combined, decreased BP to a similar
      degree, reduced albuminuria and cardiac hypertrophy to similar extent; only
      treatment regimens including sEHi increased myocardial and renal tissue
      concentrations of EETs. sEHi and EET-A, given alone or combined, suppressed
      kidney ANG II levels in TGR. Remarkably, infarct size did not significantly
      differ between TGR and Hannover Sprague-Dawley rats, but the incidence of
      ischemia-induced ventricular fibrillations was higher in TGR. Application of sEHi
      and EET-A given alone and combined sEHi and EET-A treatment were all equally
      effective in reducing life-threatening ventricular fibrillation in TGR.
      CONCLUSION: The findings indicate that chronic treatment with either sEHi or EET
      A exerts distinct antihypertensive and antiarrhythmic actions in our ANG II
      dependent model of hypertension whereas combined administration of sEHi and EET-A
      does not provide additive antihypertensive or cardioprotective effects.

PMID- 29570512
TI  - Effect of effervescent paracetamol on blood pressure: a crossover randomized
      clinical trial.
AB  - OBJECTIVE: To evaluate the effect of effervescent paracetamol on office and
      ambulatory blood pressure (BP) compared with noneffervescent paracetamol in
      hypertensive patients. DESIGN: This was a multicenter open crossover randomized
      clinical trial. SETTING: Primary care centers in Catalonia and the Basque
      Country. PARTICIPANTS: Inclusion criteria were office BP 150/95 mmHg or less and
      daytime ambulatory BP 140/90 mmHg or less, stable pharmacologic or
      nonpharmacologic antihypertensive treatment, and concomitant chronic
      osteoarticular pain. INTERVENTIONS: Baseline randomized assignment to 3-week
      periods of effervescent paracetamol (1 g three times a day) first and
      noneffervescent paracetamol later, or inversely, during a 7-week study period. At
      the start and end of each treatment period, 24-h ambulatory BP monitoring was
      performed. MAIN OUTCOME MEASURES: Differences in 24-h SBP between baseline and
      end of both treatment periods. The main analyses were performed according to the
      intention-to-treat principle. RESULTS: In intention-to-treat analysis, 46
      patients were analyzed, 21 were treated with paracetamol effervescent and
      noneffervescent later, and 25 followed the opposite sequence. The difference in
      24-h SBP between the two treatments was 3.99 mmHg (95% confidence interval 1.35
      6.63; P = 0.004), higher in the effervescent paracetamol treatment period.
      Similarly, the per-protocol analysis showed a difference in 24-h SBP between the
      two groups of 5.04 mmHg (95% confidence interval 1.80-8.28; P = 0.004), higher in
      the effervescent paracetamol treatment period. Self-reported pain levels did not
      differ between groups and did not vary by treatment period. No serious adverse
      events were reported in either study arm. CONCLUSION: Effervescent paracetamol
      tablets are responsible for a significant daytime and overall increase in
      ambulatory 24-h SBP. TRIAL REGISTRATION: NCT: 02514538 EudraCT: 2010-023485-53.

PMID- 29570511
TI  - Whole blood omega-3 fatty acid concentrations are inversely associated with blood
      pressure in young, healthy adults.
AB  - BACKGROUND: Omega-3 fatty acids (n - 3 FA) may have blood pressure (BP)-lowering
      effects in untreated hypertensive and elderly patients. The effect of n - 3 FA on
      BP in young, healthy adults remains unknown. The Omega-3 Index reliably reflects
      an individuals' omega-3 status. We hypothesized that the Omega-3 Index is
      inversely associated with BP levels in young healthy adults. METHODS: The current
      study (n = 2036) is a cross-sectional study investigating the baseline
      characteristics of a cohort, which includes healthy adults, age 25-41 years.
      Individuals with cardiovascular disease, known diabetes or a BMI higher than 35
      kg/m were excluded. The Omega-3 Index was determined in whole blood using gas
      chromatography. Association with office and 24-h BP was assessed using
      multivariable linear regression models adjusted for potential confounders.
      RESULTS: Median Omega-3 Index was 4.58% (interquartile range 4.08; 5.25).
      Compared with individuals in the lowest Omega-3 Index quartile, individuals in
      the highest had a SBP and DBP that was 4 and 2 mmHg lower, respectively (P <
      0.01). A significant linear inverse relationship of the Omega-3 Index with 24-h
      and office BP was observed. Per 1-U increase in log-transformed Omega-3 Index the
      lowering in BP (given as multivariable adjusted beta coefficients; 95% confidence
      interval) was -2.67 mmHg (-4.83; -0.51; P = 0.02) and -2.30 mmHg (-3.92; -0.68; P
      = 0.005) for 24-h SBP and DBP, respectively. CONCLUSION: A higher Omega-3 Index
      is associated with statistically significant, clinically relevant lower SBP and
      DBP levels in normotensive young and healthy individuals. Diets rich in n - 3 FA
      may be a strategy for primary prevention of hypertension.

PMID- 29570513
TI  - Three-dimensional echocardiographic ventricular mass/end-diastolic volume ratio
      in native hypertensive patients: relation between stroke volume and geometry.
AB  - BACKGROUND: Elevated left ventricular (LV) mass/end-diastolic volume ratio
      (LVM/EDV) has been associated with higher evidence of myocardial fibrosis and
      dysfunction in hypertensive patients by cardiac magnetic resonance, a technique
      with limited availability. OBJECTIVES: We investigated the ability of three
      dimensional (3D) echocardiography in identifying a phenotype of LV concentric
      geometry according to LVM/EDV ratio, possibly detecting early myocardial damage
      in native-hypertensive patients. METHODS: One hundred and twenty-eight native
      hypertensive patients underwent 2D and 3D-echocardiography. The population was
      divided into two groups, according to cut-off point values of 3D-LVM/EDV ratio
      corresponding to its upper 95% confidence interval in a population of 90 healthy
      normotensive individuals: LVM/EDV ratio cut-off was 1.22 in men and 1.23 in
      women. RESULTS: An increased 3D-LVM/EDV ratio identified a higher rate of LV
      concentric geometry in comparison with 2D-derived relative wall thickness (37
      versus 24%, P = 0.03). Patients with LVM/EDV ratio of 1.22 or more in men and
      1.23 or more in women were significantly older, had smaller 3D-LV end-diastolic
      and end-systolic volumes and higher LV mass index, without difference in ejection
      fraction. 3D-stroke volume (P < 0.0001) was lower in patients with elevated
      LVM/EDV ratio. By a multilinear regression analysis, after adjusting for sex,
      age, heart rate, mean blood pressure and BMI, stroke volume was independently and
      negatively associated to LVM/EDV ratio (beta = -0.55, P < 0.0001). CONCLUSION: In
      native hypertensive patients, 3D-echo-derived LVM/EDV ratio identifies a higher
      prevalence of LV concentric geometry than 2D-relative wall thickness. Stroke
      volume is independently and negatively associated with LVM/EDV ratio and its
      reduction represents an early marker of myocardial dysfunction in hypertensives
      with LV concentric geometry.

PMID- 29570514
TI  - Isolated systolic hypertension in the young: a position paper endorsed by the
      European Society of Hypertension.
AB  - : Whether isolated systolic hypertension in the young (ISHY) implies a worse
      outcome and needs antihypertensive treatment is still a matter for dispute. ISHY
      is thought to have different mechanisms than systolic hypertension in the
      elderly. However, findings from previous studies have provided inconsistent
      results. From the analysis of the literature, two main lines of research and
      conceptualization have emerged. Simultaneous assessment of peripheral and central
      blood pressure led to the identification of a condition called pseudo or spurious
      hypertension, which was considered an innocent condition. However, an increase in
      pulse wave velocity has been found by some authors in about 20% of the
      individuals with ISHY. In addition, obesity and metabolic disturbances have often
      been documented to be associated with ISHY both in children and young adults. The
      first aspect to consider whenever evaluating a person with ISHY is the possible
      presence of white-coat hypertension, which has been frequently found in this
      condition. In addition, assessment of central blood pressure is useful for
      identifying ISHY patients whose central blood pressure is normal. ISHY is
      infrequently mentioned in the guidelines on diagnosis and treatment of
      hypertension. According to the 2013 European Guidelines on the management of
      hypertension, people with ISHY should be followed carefully, modifying risk
      factors by lifestyle changes and avoiding antihypertensive drugs. Only future
      clinical trials will elucidate if a benefit can be achieved with pharmacological
      treatment in some subgroups of ISHY patients with associated risk factors and/or
      high central blood pressure.

PMID- 29570515
TI  - Patient-Reported Quality of Life in the Highest Functioning Patients With
      Treacher Collins Syndrome.
AB  - BACKGROUND: Treacher Collins syndrome has a wide variation of clinical
      presentation, including airway obstruction and hearing loss. The objective of
      this study was to assess patient-rated quality of life in Treacher Collins
      syndrome, who received multidisciplinary treatment at a specialized craniofacial
      hospital, and to compare their quality of life with a control sample. METHODS:
      Treacher Collins patients under treatment in a multidisciplinary setting were
      assessed with the World Health Organization Quality of Life (WHOQOL-100)
      questionnaire. The Siviero scale was used to classify quality of life as
      unsatisfactory (scores below 25), intermediate (scores between 25 and 75), and
      satisfactory (scores above 75). Quality of life comparison between Treacher
      Collins patients and 2342 unaffected individuals from a previous database was
      performed using the analysis of variance test. Differences were considered
      significant at P < 0.05. RESULTS: Treacher Collins patients demonstrated an
      overall intermediate and satisfactory (score >60%) quality of life in almost all
      WHOQOL-100 facets and domains. The comparison of the scores between unaffected
      individuals and Treacher Collins patients demonstrated a significant difference
      (P < 0.05) in the environment domain. CONCLUSION: The highest functioning
      Treacher Collins syndrome patients under multidisciplinary treatment presented
      intermediate and satisfactory quality of life, consistent with quality of life
      scores of unaffected controls. In the environment domain, Treacher Collins
      patients presented even higher scores of quality of life than the control group.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29570516
TI  - Did Anton Raphael Mengs Suffer From a Vascular Malformation?

PMID- 29570518
TI  - Surgical Treatment of Nonsyndromic Unicoronal Craniosynostosis.
AB  - PURPOSE: Unicoronal synostosis (UCS) remains one of the most difficult
      craniofacial conditions to treat. This review attempts to consolidate all
      existing literature from the past 25 years that has investigated surgical
      treatment of nonsyndromic UCS. Additional attention is paid to specific areas of
      controversy regarding surgical management and evaluation of UCS: outcomes of
      fronto-orbital advancement (FOA) versus endoscopic strip craniectomy (ESC),
      emergence of spring-associated cranioplasty for craniosynostosis, and morphologic
      assessment metrics. METHODS: A literature search from 1992 to 2017 was performed
      with a defined search strategy and manual screening process. About 24 studies
      were included in the final review. RESULTS: There is inconsistency among studies
      in measuring outcomes. Despite wide utilization, FOA produces mixed results,
      especially when looking at long-term outcomes. Preliminary data suggest
      advantages to using ESC over FOA with regard to facial symmetry, postoperative
      strabismus, and operating time. Distraction osteogenesis has long been utilized
      in Asia and is now being actively studied in the United States. Data on spring
      assisted cranioplasty are lacking. Long-term results at skeletal maturity for
      many of these techniques are lacking. DISCUSSION: Despite some promising results,
      methods of measurement are inconsistent and long-term data are lacking. All
      future research in this area would benefit from consistent and standardized
      reporting of data, including perioperative statistics and reproducible 3
      dimensional computed tomography craniofacial measurements. Additionally, no
      definitive recommendations can be made until data at skeletal maturity are
      studied, and all studies would benefit from long-term follow-up data.

PMID- 29570517
TI  - Percutaneous Screws and External Fixation in Frontal Sinus Anterior Wall
      Fractures.
AB  - Fractures of the frontal sinus are frequently encountered injuries of
      maxillofacial fractures. The most common causes are traffic accidents, followed
      by sports-related injuries. There is still no consensus regarding the optimal
      management of frontal sinus fractures. The authors report a patient with
      depressed anterior wall fracture of the frontal sinus and superior orbital rim
      fracture. Reduction was performed by traction from 2 screws applied
      percutaneously to the depressed fragments and external fixation with an aluminum
      nasal splint. This technique is both minimally invasive and permits easy fixation
      in suitable patients.

PMID- 29570519
TI  - Cystic Progression of a Cavernous Malformation at the Level of the Trigeminal
      Root Entry Zone Presenting With Sudden Onset of Trigeminal Neuralgia.
AB  - BACKGROUND: Cavernous malformations (CM) in the cerebellopontine angle (CPA) are
      rare, and most of them are solid and extend from the internal auditory canal into
      the CPA. In contrast, cystic CM arising in the CPA and not involving the internal
      auditory canal and dura of the skull base are extremely rare. The authors present
      an uncommon large cystic progression of a cavernous malformation at the level of
      the trigeminal root entry zone evolving to severe trigeminal neuralgia and
      brainstem compression. METHODS: A 62-year-old female presented a sudden onset of
      left trigeminal neuralgia, caused by a large cystic lesion at the level of the
      root entry zone of the left 5th nerve. On neurological examination, she showed
      slight gait ataxia and hypoesthesia on the left hemiface (on the first and second
      trigeminal branches). Other cranial nerves were in order. Magnetic resonance
      imaging showed a large cystic intracranial mass, with a small solid portion,
      leading to brainstem compression. RESULTS: Microsurgical removal of the lesion
      was performed via retrosigmoid approach, with intraoperative monitoring of somato
      sensory evoked potentials, facial, and cochlear nerves. The posterior-medial
      portion of the lesion was solid, whereas the main portion was cystic, containing
      xanthochromic fluid. The small solid lesion continued with a thin capsule of a
      large cyst adherent to brainstem, cerebellar hemisphere, and trigeminal nerve
      entry zone. A big draining vein arising from the solid part of the lesion runned
      parallel to brainstem. The mass was piecemeal totally removed.After surgery the
      patient recovered both left trigeminal neuralgia and hypoesthesia; ataxia was
      significantly relieved too. Postoperative magnetic resonance imaging confirmed
      the total removal. Histopathological features were consistent with a CM. At 6
      month follow-up, patient's symptoms at the presentation had resolved. CONCLUSION:
      The authors present a very rare patient of large cystic cavernous malformation at
      the level of the trigeminal root entry zone presenting with sudden onset of
      trigeminal neuralgia. Even if it has not established imaging features, a cystic
      cavernoma of the cerebello-pontine angle may be suspected when a cystic mass is
      present, not involving the internal acoustic meatus nor the skull base dura
      mater. Careful microneurosurgical technique and monitoring of cranial nerves
      allow good long-term results.

PMID- 29570520
TI  - Stranger Things: A Whimsical Account of a Demineralized Bone Matrix Study With
      Unexpected Results.

PMID- 29570522
TI  - Allotransplantation: From Dream to Reality.

PMID- 29570521
TI  - Evaluation of Fibrin Clot Attachment on Titanium Laser-Conditioned Surface Using
      Scanning Electron Microscopy.
AB  - OBJECTIVES: The study aimed to evaluate the effects of different titanium surface
      treatments on blood clot extension (bce). METHODS: A total of 54 titanium disks
      with machined surface (M), laser-conditioned surface (L), and grit-blasted
      surface (S) were used in the present study. The surface characteristics such as
      contact angles and the microroughness were determined on each group (n = 4). To
      evaluate the bce, 0.1 mL of human blood was dropped onto the surface of each
      specimen and left for 7 minutes at room temperature. After fixation, dehydration,
      and gold sputtering treatments, the specimens were observed under scanning
      electron microscope. The bce values were expressed as percentage of specimen
      surface covered by blood clot. RESULTS: The surface roughness (Ra +/- standard
      deviation [SD]) was 0.75 +/- 0.02 MUm for M, 0.25 +/- 0.02 MUm for L, and 1.30 +/
      0.03 MUm for S. The contact angles measured in static conditions (WCA +/- SD)
      were 71 +/- 5.4 degrees  for M, 107 +/- 6.6 degrees  for L, and 91 +/- 7.2
      degrees  for S. Regarding the bce (bce +/- SD) of M samples (65.5 +/- 4.3%) was
      statistically lower compared with both L (83.4 +/- 5.1%) and S samples (72.4 +/-
      4.7%) (P < 0.05). Meanwhile, the L group showed the higher bce value. CONCLUSION:
      The present results suggest that the laser-conditioned surface may increase the
      wettability and bce.

PMID- 29570523
TI  - Review of "Prevalence of Needlestick Injuries, Attitude Changes, and Prevention
      Practices Over 12 Years in an Urban Academic Hospital Surgery Department" by
      Hasak JM, Novak CB, Patterson JMM, Mackinnon SE in Ann Surg 267: 291-296, 2018.

PMID- 29570524
TI  - Treatment of an Uncommon High-Pressure Orbital Injection Injury.
AB  - Injection injuries occur most commonly in the hand and digits; however, there are
      a limited number of reports in the literature describing injection injuries
      involving the orbit. High-pressure orbital injection injuries pose a number of
      unique challenges to the treating physician, and the approach to treating these
      injuries remains controversial. Often times, the extent of tissue damage is not
      fully appreciated at presentation, which may lead to missed diagnoses or
      inadequate initial treatment. In this study, the authors describe a rare
      incidence of high-pressure orbital injection injury. A 19-year-old male presented
      to the emergency department after injection of his left orbit with oil-based
      paint. Worsening clinical symptoms and increasing intraocular pressures within
      the first 24 hours necessitated take back to the operating room for orbital
      decompression and debridement. After an initial improvement in symptoms, the
      patient's clinical status deteriorated again, requiring further orbital
      decompression and additional periorbital debridement. Two weeks after initial
      presentation, soft tissue reconstruction of the surgical wounds was performed
      with full thickness skin grafts. The patient's globe and vision were both
      preserved. Orbital injection injuries, though rare, are potential globe
      threatening injuries. Physicians should have a low threshold for intervention and
      patient's must be observed closely over the first 72 hours after injury. Early
      diagnosis, prompt debridement, and a multidisciplinary approach are keys to
      improving patient outcomes.

PMID- 29570525
TI  - Novel Application of Ultrasonic Bone Aspirator for Hump Nose.
AB  - OBJECTIVE: This study was conducted to introduce and evaluate the efficacy of an
      ultrasonic bony aspirator in rhinoplasty for hump removal. DESIGN: Retrospective
      study. SETTING: University medical center. PATIENTS: Twenty patients who
      underwent hump removal using an ultrasonic bone aspirator from October 2013 to
      November 2016 were enrolled in the study. MAIN OUTCOME MEASURES: Patients were
      followed for >3 months after surgery. External nose status and surgical results
      were investigated using photographs. Postoperative complications were evaluated.
      RESULTS: Of the 30 patients enrolled in this study, 11 were females and 19 were
      males. Preoperative nasal deformities of all patients were characterized as bony
      humps. Postoperative dorsal status was significantly improved. There were no
      obvious complications such as over or under correction, delayed healing,
      infection, soft tissue injury, or deformity of the nasal dorsum. CONCLUSION:
      Application of an ultrasonic bone aspirator to remove humps in rhinoplasty is
      easy, safe, and effective.

PMID- 29570526
TI  - An Unusual Case of Headache: Isolated Fungus Ball in Concha Bullosa.
AB  - A concha bullosa forms when the middle turbinate becomes pneumatized, which is a
      common anatomic variation; however, fungus ball in concha bullosa is rather rare.
      An otherwise healthy 52-year-old man presented to our ear, nose and throat clinic
      with the complaints of midfacial pressure headache and malodorous postnasal drip.
      Computed tomography of the paranasal sinuses demonstrated a polypoid hyperdense
      lesion with slight microcalcifications in the right nasal cavity, accompanied
      with a complicated fluid collection in the right frontoethmoideal recess seen as
      hypodensity in contrast to this hyperdensity. The histopathological examination
      reported a fungal infection. We present an extremely rare case of isolated fungal
      mass in the right middle concha detected in an early stage without any evidence
      of fungal infection of the other paranasal sinuses and discuss the importance of
      reevaluation of the computed tomography scans in suspicion of a fungal sinusitis.

PMID- 29570527
TI  - Accessory Submandibular Salivary Gland Forming a "Horseshoe" With the Main
      Submandibular Salivary Gland: A Unique Variation.
AB  - Presence of accessory submandibular salivary gland (ASSG) is an extremely rare
      variation. Knowledge of its relations could be very useful to oral and
      maxillofacial surgeons, head and neck surgeons, and radiologists. During
      dissection classes, an ASSG was noted between the mylohyoid and hyoglossus
      muscles. The main submandibular salivary gland had superficial and deep parts.
      The deep part was narrow and measured about 5 cm. The lingual nerve passed
      between the superficial and deep parts. The accessory submandibular gland was
      situated below and parallel to the deep part of SSG. It also measured 5 cm. The
      ASSG had its own duct, which joined the duct of main gland. The ASSG and the deep
      part of the SSG were united at the lateral border of geniohyoid muscle to give a
      characteristic "horseshoe" appearance. The ASSG overlapped both lingual and
      hypoglossal nerves.

PMID- 29570528
TI  - Zygomaticofacial, Zygomaticoorbital, and Zygomaticotemporal Foramina.
AB  - This study aimed to assess the anatomical and morphometric characteristics of the
      main zygomaticofacial (ZFF), zygomaticoorbital (ZOF), and zygomaticotemporal
      (ZTF) foramina in Brazilian dry skulls. 61, 69, and 42 skulls for ZFF, ZOF, and
      ZTF were evaluated by a single calibrated examiner for format, transverse and
      vertical diameters, and distances from the foramina to anatomical landmarks.
      Paired t test, Wilcoxon test, Pearson and Spearman correlations were used.
      Circular outline was the predominant format for ZFF and ZTF, while oval format
      was the most frequent for ZOF. Median distances from ZFF to frontozygomatic and
      zygomaticomaxillary sutures were higher on right and left sides of the skulls,
      respectively (P < 0.005). Mean ZOF transverse diameter was significantly higher
      on the right sides of the skulls and presented positive correlation between sides
      (P < 0.05). No differences were observed for mean vertical diameter and distance
      from the ZOF to the inferolateral angle of the orbit (P > 0.05). No significant
      difference was found for distance from the ZTF to zygomatic arch between sides (P
      > 0.05), although there was a positive correlation (P < 0.05). Significant
      differences were found when analyzing the anatomical and morphometric aspects of
      ZFF, ZOF, and ZTF.

PMID- 29570529
TI  - Surgical Treatment of Rhinosinusitis-Related Orbital Complications: Factors
      Affecting Irreversible Blindness.
AB  - If left untreated, rhinosinusitis can rarely cause a devastating complication
      irreversible blindness (IB). Despite new technologies in endoscopic sinus surgery
      and use of new broad-spectrum antibiotics, IB outcome is still a problem for
      surgically treated orbital complication of paranasal sinus infection (OCPSI)
      patients, and factors leading to IB outcome are not actually known. The aim of
      this study was to assess the factors leading to the IB outcome for surgically
      treated OCPSI patients. Results of 25 surgically treated OCPSI patients in our
      clinic were combined with surgically treated OCPSI patients reported through the
      PubMed database search from the year 2007. Patients were divided into 2 groups:
      IB group and recovery group. Patients having at least 1 immune status-related
      additional risk factor (ARF) were more common in the IB group, having an at least
      1 ARF had 1.683 risk value of IB outcome (RR: 1.683, P = 0.006). IB patients had
      statistically significant higher mean (21.87 +/- 40.35, P = 0.005) time interval
      (days) (TI) between onset of ophthalmological symptoms and surgical intervention
      compared to recovery group patients (2.92 +/- 2.53). ROC curve analysis for an
      estimation of IB outcome according to the TI value demonstrated that a cut-off
      value of >=2.5 days had the ideal sensitivity (87.5%) and specificity (71.9%)
      that resulted in IB outcome. (80.5% power, P = 0.008) IB and recovery group
      patients did not differ according to orbital complication type according to
      Chandler's classification (P = 0.492) and white blood cell count status (P =
      0.584). In conclusion, OCPSI patients with ARFs and delayed admission after onset
      of orbital symptoms have a higher risk of IB outcome. These patients deserve
      prompt evaluation and early surgical intervention to prevent blindness. With
      future studies, new surgical criteria, including the ARF status and onset of
      ophthalmological symptoms (>=2.5 days) may be added to classical surgical
      criteria to prevent IB for OCPSI cases.

PMID- 29570530
TI  - The "Flap Suture Anchoring" Technique for Safe Oral Floor Reconstruction With
      Preservation of Alveolar Process.
AB  - Flaps-based microsurgery is routinely applied to reconstruct oral floor defects
      caused by oncologic resection. To prevent orocutaneous fistulae, flaps are
      frequently sutured with buccal vestibule mucosa after sacrificing the alveolar
      process. The patients suffered denture loss and irreversible structural damage.
      For reliable oral floor reconstruction with preservation of alveolar process, the
      authors introduced the flap "suture anchoring" technique. Oral floor, hemiglossal
      oral floor, and tongue base-parapharyngeal wall-oral floor defects were included
      in this study. The flap anchoring technique involves structural oral floor
      reconstruction with a chimeric anterolateral thigh-free flap or radial forearm
      flap with adipofascial tissue extension. The dead space in oral floor is filled
      with vastus lateralis muscle or adipofascial tissue, then holes are drilled on
      the alveolar bone among tooth root, beneath the attached gingiva. Skin paddle is
      sutured with 4-0 sutures through the alveolar holes thus anchored to the
      mandible. By applying this technique, there was no wound infection or
      orocutaneous fistulae in all patients postoperatively, even experienced
      postoperative radiotherapy. In addition, a soft and natural jaw-tongue furrow
      could be formed to allow the free movement of tongue. Taken together, the flap
      anchoring technique offers a safe and reliable approach to recover oral function
      and preservation of occlusion.

PMID- 29570531
TI  - Simultaneous Implant Placement in a Mandibular Defect Reconstructed With a Free
      Fibula Graft and Fabrication of a Fixed Metal Porcelain Prosthesis.
AB  - This clinical report presents the multidisciplinary treatment approach for a 23
      year-old male patient who underwent a total mandibular reconstruction due to
      trauma in the past and experienced postoperative complications. For his
      retreatment, exposed fixation plate was removed and infected bone was debrided
      and then a free fibula graft augmentation with simultaneous implant placement
      procedure was performed. After an osseointegration period of 6 months, a screw
      retained porcelain fused to metal fixed prosthesis was fabricated and delivered.

PMID- 29570532
TI  - Endoscopic Transsphenoidal Surgery for an Adult Patient With Giant Exophytic
      Chiasmatic/Hypothalamic Glioma.
AB  - Optic pathway hypothalamic gliomas are intrinsic low-grade gliomas involving the
      optic nerve, chiasm, optic tract, and hypothalamus. The rarity of these tumors
      and their unpredictable course make assessment and standardization of treatment
      modalities difficult. Tumor debulking via various transcranial approaches was
      considered to be effective at controlling tumor growth, but with high rates of
      severe surgery-related complications. In the present case, endoscopic
      transsphenoidal surgery was initiated to debulk the exophytic
      chiasmatic/hypothalamic glioma with good preservation of hypothalamic and
      endocrine functions. The authors suggest transsphenoidal surgery with tumor
      debulking could be an effective and safe treatment for patients with
      chiasmatic/hypothalamic gliomas.

PMID- 29570533
TI  - Subunit Reconstruction of Mid-Facial Defects With Free Style Facial Perforator
      Flaps.
AB  - INTRODUCTION: Reconstruction of facial defects is not only important for cosmesis
      but also for the function. Local flaps are considered the best reconstruction
      method for facial defects. The authors want to show the feasibility of free style
      facial perforator flap for the reconstruction of moderate sized mid-facial
      defects. METHODS: Free style facial artery and lateral nasal artery perforator
      flaps were performed in 22 patients (11 males and 11 females) who had removal of
      facial tumor between March 2015 and December 2016 RESULTS:: The median age of
      patients was 62 years (range: 35-84). The mean follow-up period was 12.6 months
      (range: 5-24). Pathology results were basal cell carcinoma in 13 patients,
      squamous cell carcinoma in 6 patients, and other skin tumors in 3 patients. The
      defect size ranged from 2 * 2 to 5 * 5 cm. No major or minor complication
      happened but 1 flap had venous congestion that healed without any intervention
      CONCLUSION:: Free style facial perforator flaps are highly reliable flaps with
      wide range of motion. In addition, they provide single-stage closure with
      esthetic subunit reconstruction. With the current knowledge of reconstruction and
      skills of microsurgery, they can be easily the first choice for the closure of
      mid-facial defects.

PMID- 29570534
TI  - Neuromuscular Adaptations to Work-matched Maximal Eccentric versus Concentric
      Training.
AB  - : It is unclear whether the superiority of eccentric over concentric training on
      neuromuscular improvements is due to higher torque (mechanical loading)
      achievable during eccentric contractions or due to resulting greater total work.
      PURPOSE: This study aimed to examine neuromuscular adaptations after maximal
      eccentric versus concentric training matched for total work. METHODS: Twelve
      males conducted single-joint isokinetic (180 degrees .s) maximal eccentric
      contractions of the knee extensors in one leg (ECC-leg) and concentric in the
      other (CON-leg), 6 sets per session (3-5 sets in the initial 1-3 sessions), 2
      sessions per week for 10 wk. The preceding leg performed 10 repetitions per set.
      The following leg conducted the equivalent volume of work. In addition to peak
      torque during training, agonist EMG and MRI-based anatomical cross-sectional area
      (ACSA) and transverse relaxation time (T2) at midthigh as reflective of neural
      drive, hypertrophy, and edema, respectively, were assessed weekly throughout the
      training period and pre- and posttraining. Whole muscle volume was also measured
      pre- and posttraining. RESULTS: Torque and EMG (in trained contraction
      conditions) significantly increased in both legs after week 1 (W1) and week 4
      (W4), respectively, with a greater degree for ECC-leg (torque +76%, EMG +73%:
      posttraining) than CON-leg (+28%, +20%). ACSA significantly increased after W4 in
      ECC-leg only (+4%: posttraining), without T2 changes throughout. Muscle volume
      also increased in ECC-leg only (+4%). Multiple regression analysis revealed that
      changes (%Delta) in EMG solely explained 53%-80% and 30%-56% of the total
      variance in %Deltatorque through training in ECC-leg and CON-leg, respectively,
      with small contributions (+13%-18%) of %DeltaACSA for both legs. CONCLUSION:
      Eccentric training induces greater neuromuscular changes than concentric training
      even when matched for total work, whereas most of the strength gains during 10-wk
      training are attributable to the increased neural drive.

PMID- 29570535
TI  - Overview of the NASA 70-day Bed Rest Study.
AB  - PURPOSE: The purpose of this article was to provide an overview of the National
      Aeronautics and Space Administration (NASA) 70-day Bed Rest Study. The integrated
      complement of investigations and the standardized bed rest environment that
      served as the platform for this study complement are described. Outcomes of the
      studies will not be presented here but will be reported in separate publications.
      METHODS: A set of studies running in an integrated fashion along the entire
      period (pre-, in-, and post-bed rest) and using the same subjects is referred in
      this article as "the campaign" or "complement." NASA selected eight individual
      studies to participate in the 70-d bed rest campaign. These studies were
      integrated to increase efficiency in the utilization of resources and to share
      common measures among the investigations. In addition to the individual studies
      addressing specific aims, a battery of standardized measures was included.
      Standard measures target a wide range of physiologic systems and represent some
      of the testing routinely done on astronauts. Bed rest subjects underwent rigorous
      medical and psychological screening. Standardized conditions included 70 d of bed
      rest in a 6 degrees  head-down tilt position. Subjects' vital signs, body weight,
      and fluid intake and output were measured daily. A standardized diet was provided
      to ensure consistent nutritional intake across subjects. Exercising subjects were
      prescribed individualized aerobic and resistance training 6 d.wk performed in a
      horizontal body position. Subjects in the testosterone supplementation
      countermeasure group received testosterone enanthate injections at 2-wk intervals
      during bed rest. CONCLUSION: Long-duration head-down tilt bed rest provided a
      suitable platform for examining physiologic effects of spaceflight and testing
      countermeasures in a ground-based model. Integrating studies into a complement is
      an effective way to support multiple investigations while minimizing the number
      of subjects to answer many research questions.

PMID- 29570537
TI  - Myocellular Responses to Concurrent Flywheel Training during 70 Days of Bed Rest.
AB  - PURPOSE: This investigation evaluated myocellular responses to an integrated
      resistance and aerobic training program during 70 d of bed rest. METHODS:
      Training was 6 d.wk on a small-footprint gravity-independent flywheel resistance
      and aerobic device; 3 d of maximal flywheel supine quadriceps and calf exercises
      with continuous rowing separated by 4 to 6 h, and 3 d of interval rowing. Vastus
      lateralis (VL) and soleus (SOL) muscle biopsies were obtained from eight healthy
      males (age, 28 +/- 4 yr; BMI, 25 +/- 3 kg.m; VO2max, 42 +/- 6 mL.kg.min) before
      and after 6 degrees  head-down tilt bed rest. Vastus lateralis and SOL myosin
      heavy chain (MHC) I and IIa single muscle fiber size and functional
      characteristics, as well as overall fiber type distribution, capillarization, and
      metabolic enzyme activities were evaluated. RESULTS: In the VL, MHC I size and
      power (absolute and normalized) were preserved. The MHC IIa fibers hypertrophied
      (+6%, P < 0.05) without a change in absolute power, so normalized power declined
      (-7%, P < 0.05). In the SOL, MHC I fibers atrophied (-9%) and absolute power
      declined (-17%) (P < 0.05), whereas normalized power was maintained. Size,
      absolute power, and normalized power were protected in the less-abundant MHC IIa
      fibers. Reduced MHC coexpressing hybrid fibers, generally indicative of an
      exercise training effect, was apparent in the VL, whereas fiber type was
      maintained in the SOL. Capillarization and metabolic enzymes were generally
      preserved or increased in VL and SOL. CONCLUSIONS: The integrated resistance and
      aerobic training protocol on a device maintains several key myocellular
      characteristics during prolonged unloading, but further refinement of the
      exercise approach to fully protect the SOL is warranted.

PMID- 29570538
TI  - Acute Effect of Noradrenergic Modulation on Motor Output Adjustment in Men.
AB  - PURPOSE: To determine the role of noradrenergic modulation in the control of
      motor output, we compared the acute effect of reboxetine (REB), a noradrenaline
      reuptake inhibitor, to a placebo (PLA) on knee extensors motor performance and
      cortical and spinal excitability. METHODS: Eleven young men took part in two
      randomized experiments during which they received either 8 mg of REB or a PLA.
      The torque produced during a maximal voluntary contraction (MVC) and its
      variability (i.e., coefficient of variation) during submaximal contractions
      ranging from 5% to 50% MVC were measured. Paired electrical (PES) and
      transcranial magnetic stimulation (TMS) were used to assess changes in voluntary
      activation during MVC, and corticospinal (motor-evoked potential (MEP)) and
      spinal excitability (Hoffmann (H) reflex) during contraction at 20% MVC. RESULTS:
      MVC torque and torque steadiness increased respectively by 9.5% and 24% on
      average in REB compared with PLA condition (P < 0.001). Voluntary activation
      tested by TMS and PES was greater (~3%; P < 0.05) in REB than PLA condition. The
      increase in voluntary activation in REB condition was significantly correlated
      with subjects' initial voluntary activation level when tested by TMS (r = -0.62;
      P = 0.048) and PES (r = -0.86; P < 0.01). The maximal amplitudes of H reflex and
      MEP and the slope of their recruitment curves were enhanced by REB (P < 0.05).
      The ratio between the TMS-induced EMG silent period and the corresponding MEP
      (silent period/MEP) was reduced in REB condition (P < 0.01). CONCLUSIONS: The
      present findings indicate that voluntary activation and accuracy in force control
      can be increased by an enhanced level of noradrenaline concentration. This
      improvement in motor performance is accompanied by changes located at both
      cortical and spinal levels.

PMID- 29570536
TI  - Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular
      Remodeling.
AB  - PURPOSE: Early and consistent evaluation of cardiac morphology and function
      throughout an atrophic stimulus is critically important for the design and
      optimization of interventions. This randomized controlled trial was designed 1)
      to characterize the time course of unloading-induced morphofunctional remodeling
      and 2) to examine the effects of exercise with and without low-dose testosterone
      supplementation on cardiac biomarker, structural, and functional parameters
      during unloading. METHODS: Twenty-six subjects completed 70 d of head-down tilt
      bed rest (BR): 9 were randomized to exercise training (Ex), 8 to EX and low-dose
      testosterone (ExT), and 9 remained sedentary (CONT). Exercise consisted of high
      intensity, continuous, and resistance exercise. Cardiac morphology (left
      ventricular mass [LVM]) and mechanics (longitudinal, radial, and circumferential
      strain and twist), cardiovascular biomarkers, and cardiorespiratory fitness
      (VO2peak) were assessed before, during, and after BR. RESULTS: Sedentary BR
      resulted in a progressive decline in LVM, longitudinal, radial, and
      circumferential strain in CONT, whereas Ex and ExT mitigated decreases in LVM and
      function. Twist was increased throughout BR in sedentary BR, whereas after an
      initial increase at BR7, there were no further changes in twist in Ex and ExT.
      HDL cholesterol was significantly decreased in all groups compared with pre-BR (P
      < 0.007). There were no significant changes in other cardiovascular biomarkers.
      Change in twist was significantly related to change in VO2max (R = 0.68, P <
      0.01). CONCLUSION: An integrated approach with evaluation of cardiac morphology,
      mechanics, VO2peak, and biomarkers provides extensive phenotyping of
      cardiovascular atrophic remodeling. Exercise training and exercise training with
      low-dose testosterone supplementation abrogates atrophic remodeling.

PMID- 29570539
TI  - Comparison between Slow Components of HR and VO2 Kinetics: Functional
      Significance.
AB  - PURPOSE: Aerobic exercise prescription is often based on a linear relationship
      between pulmonary oxygen consumption (VO2) and heart rate (HR). The aim of the
      present study was to test the hypothesis that during constant work rate (CWR)
      exercises at different intensities, the slow component of HR kinetics occurs at
      lower work rate and is more pronounced that the slow component of VO2 kinetics.
      METHODS: Seventeen male (age, 27 +/- 4 yr) subjects performed on a cycle
      ergometer an incremental exercise to voluntary exhaustion and several CWR
      exercises: 1) moderate CWR exercises, below gas exchange threshold (GET); 2)
      heavy CWR exercise, at 45% of the difference between GET and VO2 peak (Delta); 3)
      severe CWR exercise, at 95% of Delta; 4) "HRCLAMPED" exercise in which work rate
      was continuously adjusted to maintain a constant HR, slightly higher than that
      determined at GET. Breath-by-breath VO2, HR, and other variables were determined.
      RESULTS: In moderate CWR exercises, no slow component of VO2 kinetics was
      observed, whereas a slow component with a relative amplitude (with respect to the
      total response) of 24.8 +/- 11.0% was observed for HR kinetics. During heavy CWR
      exercise, the relative amplitude of the HR slow component was more pronounced
      than that for VO2 (31.6 +/- 11.2% and 23.3 +/- 9.0%, respectively). During
      HRCLAMPED, the decrease in work rate (~14%) needed to maintain a constant HR was
      associated with a decreased VO2 (~10%). CONCLUSIONS: The HR slow component
      occurred at a lower work rate and was more pronounced than the VO2 slow
      component. Exercise prescriptions at specific HR values, when carried out for
      periods longer than a few minutes, could lead to premature fatigue.

PMID- 29570541
TI  - Your Next Professional Step ... Becoming an Author.

PMID- 29570540
TI  - Discovering the Tiny Warrior Within.

PMID- 29570542
TI  - Caring for the Orthopaedic Patient With a History of Bariatric Surgery.
AB  - Bariatric surgery is performed on the gastrointestinal tract as a solution to
      obesity, and prevalence of these surgical procedures continues to rise. Bariatric
      surgery creates restrictive and/or malabsorptive properties, causing nutritional
      deficits from the physiological changes in absorption and a hypoacidic
      environment. Although surgery induces sustained weight loss, decreases mortality,
      and provides resolution or improvement to comorbidities of obesity, it can also
      come with complications. Common long-term complications of bariatric surgery
      include malnutrition, anemia, impaired wound healing, and impaired bone health.
      It is essential that nurses and the healthcare team caring for orthopaedic
      individuals with a history of bariatric surgery be aware of the special needs of
      these individuals, especially in the promotion of bone health. Using a
      multidisciplinary approach for the advancement of the orthopaedic patient's
      health will help promote quality patient care.

PMID- 29570543
TI  - Caring for the Orthopaedic Patient With a History of Bariatric Surgery.

PMID- 29570545
TI  - Developing and Testing an International Audit of Nursing Quality Indicators for
      Older Adults With Fragility Hip Fracture.

PMID- 29570544
TI  - Developing and Testing an International Audit of Nursing Quality Indicators for
      Older Adults With Fragility Hip Fracture.
AB  - BACKGROUND: Fragility hip fracture in older adults often has poor outcomes, but
      these outcomes can be improved with attention to specific quality care
      indicators. PURPOSE: The International Collaboration of Orthopaedic Nursing
      (ICON) developed an audit process to identify the extent to which internationally
      accepted nursing quality care indicators for older adults with fragility hip
      fracture are reflected in policies, protocols, and processes guiding acute care.
      METHODS: A data abstraction tool was created for each of 12 quality indicators.
      Data were collected using a mixed-methods approach with unstructured rounds. A
      rationale document providing evidence for the quality indicators and a user
      evaluation form were included with the audit tool. A purposeful sample of 35
      acute care hospitals representing 7 countries was selected. RESULTS: Thirty-five
      hospitals (100%) completed the survey. Respondents viewed the content as relevant
      and applicable for the defined patient population. Although timing and frequency
      of implementation varied among and within countries, the identified quality
      indicators were reflected in the majority of policies, protocols, or processes
      guiding care in the hospitals surveyed. CONCLUSION: Developing and testing an
      audit of nurse-sensitive quality indicators for older adults with fragility hip
      fracture demonstrate international consensus on common core best practices to
      ensure optimal acute care.

PMID- 29570547
TI  - Impact of Music Therapy on Hospitalized Patients Post-Elective Orthopaedic
      Surgery: A Randomized Controlled Trial.

PMID- 29570546
TI  - Impact of Music Therapy on Hospitalized Patients Post-Elective Orthopaedic
      Surgery: A Randomized Controlled Trial.
AB  - BACKGROUND: Music therapy (MT) research has demonstrated positive effects on
      fatigue, depressed mood, anxiety, and pain in perioperative care areas. However,
      there has been limited research on the effects of MT for surgical patients on
      orthopaedic units. PURPOSE: The purpose of this study was to understand the
      impact of MT sessions on post-elective orthopaedic surgery patients' pain, mood,
      nausea, anxiety, use of narcotics and antiemetics, and length of stay. METHODS:
      This was a randomized controlled study with an experimental arm (MT sessions) and
      a control arm (standard medical care). Patients received MT within 24 hours of
      admission to the unit, as well as every day of their stay. Same-day pre- and
      postdata were collected 30 minutes apart for both arms, including patient self
      reported mood, pain, anxiety, and nausea. Use of medications and length of stay
      were gleaned from the electronic medical record. RESULTS: Data were obtained for
      163 patients, age 60.5 +/- 11.1 years, 56% of whom were male. Joints targeted by
      surgeries were hips (54%), knees (42%), and shoulders (4%). There were
      significantly greater changes favoring the MT group on Day 1 (pain, anxiety, and
      mood), Day 2 (pain, anxiety, mood, and nausea), and Day 3 (pain, anxiety, and
      mood). Among participants with a pre-pain score of 2 or more on Day 1, a decrease
      of at least 2 points was noted in 36% of the MT group and 10% of the control
      group (P < .001). Overall, 73% of MT patients versus 41% of control patients
      reported improved pain (P < .001). No significant between-group differences in
      medications or length of stay were noted. CONCLUSIONS: We observed greater same
      day improvements of pain, emotional status, and nausea with MT sessions, compared
      to usual care, in patients hospitalized after elective orthopaedic surgeries.
      Effects on narcotic and antiemetic usage, as well as length of stay, were not
      observed. More research needs to be conducted to better understand the benefits
      of MT pre- and post-elective orthopaedic surgery.

PMID- 29570548
TI  - Intrathecal Baclofen Therapy Prior to Spinal Fusion for Patients With Gross Motor
      Function Classification System IV-V Cerebral Palsy.
AB  - BACKGROUND: Patients with Gross Motor Function Classification System (GMFCS) IV-V
      cerebral palsy (CP) have significant spasticity and frequently develop scoliosis.
      Intrathecal baclofen (ITB) pumps are effective in managing spasticity. The effect
      of ITB therapy on the postoperative course following spinal fusion in patients
      with GMFCS IV-V CP has not been described. This study sought to compare
      postoperative recovery, including complications, in patients using ITB therapy
      with those with no ITB therapy. PURPOSE: Evaluate the effect of ITB on the
      postoperative recovery for patients with GMFCS IV-V CP who undergo spinal fusion
      for scoliosis. METHODS: Health records for patients with GMFCS IV-V CP who
      underwent a spinal fusion for scoliosis at a major quaternary-care children's
      hospital from January 2009 to October 2015 were reviewed and relevant data were
      abstracted. Descriptive statistics and regression models were used to compare
      patients. RESULTS: Sixty-nine patients were included-19 ITB therapy and 50 no ITB
      therapy. Demographic and operative characteristics were similar across groups.
      The mean length of stay for patients in the ITB therapy group was 11.2 days and
      14.3 days for the no ITB therapy group, with no difference between groups (p =
      .12). Pain scores in both groups decreased at the same rate, with scores in the
      ITB therapy group averaging one-half point lower (p = .32). The average amount of
      morphine equivalents (p = .71) and benzodiazepine equivalents (p = .53) used were
      similar between groups. Complication rates were significantly different between
      groups. Four (21%) of the ITB therapy patients had 1 or more complications
      whereas 28 (56%, p = .01) in the no ITB therapy group had 1 or more
      complications. The average number of complications per patient in the ITB therapy
      group was 0.3 (SD: 0.075, range: 0-3) and the no ITB therapy group was 1.1 (SD:
      1.1, range: 0-6, p = .01). CONCLUSIONS: There was no significant difference in
      length of stay, pain scores, or pain/spasticity medication use between groups
      after spinal fusion, but there was a significantly lower incidence of
      complications in the ITB therapy group.

PMID- 29570549
TI  - Skin Laceration in Collagenase Clostridium histolyticum Treatment for Dupuytren's
      Contracture.
AB  - BACKGROUND: Dupuytren's contracture produces a progressive flexion contracture of
      the affected fingers. Collagenase Clostridium histolyticum produces breakdown of
      the cord in the hand and/or finger(s) that tightens as a result of the disease
      creating a contracture, allowing manual traction and cord rupture. One of the
      side effects is spontaneous skin laceration when the finger is extended.
      OBJECTIVES: To evaluate the development of skin lacerations in Dupuytren's
      contracture treated with collagenase Clostridium histolyticum, to determine
      predisposing factors, and evaluate the effectiveness of 2 different treatments
      (antiseptic and non-antiseptic dressings). PARTICIPANTS: Included 157 patients
      diagnosed with Dupuytren's contracture and treated with collagenase Clostridium
      histolyticum. METHODS: Analysis of variables and logistic regression model were
      applied to determine their possible relationship with skin lacerations. The
      effectiveness of the type of treatment used was evaluated by comparing the amount
      of time required for healing. RESULTS: Skin lacerations were present in 33.1% (n
      = 52) of patients, with an average laceration length of 1.12 (SD: 0.70) cm.
      Characteristics that were significant predisposing factors for lacerations were
      disease bilateralism (p = .002), previous surgical intervention (p = .003), and
      initial matacarpophalangeal joint contracture (p < .001). Worse initial
      contracture (Z = 5.94; p < .001) had a greater risk of laceration as did those
      who had prior hand surgery, or whose little finger was affected. Average
      treatment length of healing was 11.24 days (SD: 8.13). All wounds healed
      successfully. There were no significant differences (p = .511) in healing between
      different dressings evaluated. CONCLUSIONS: Skin lacerations as a consequence of
      treating Dupuytren's contracture with collagenase Clostridium histolyticum occur
      often and are moderately serious. For all cases, evolution is satisfactory in
      less than 2 weeks, and the type of treatment does not appear to make any
      difference in healing time.

PMID- 29570551
TI  - Rotator Cuff Tear.

PMID- 29570550
TI  - Rotator Cuff Tear.

PMID- 29570552
TI  - Nursing Leadership: Two Books.

PMID- 29570554
TI  - Paediatric Intestinal Pseudo-obstruction: Evidence and Consensus-based
      Recommendations From an ESPGHAN-Led Expert Group.
AB  - OBJECTIVES: Chronic intestinal pseudo-obstructive (CIPO) conditions are
      considered the most severe disorders of gut motility. They continue to present
      significant challenges in clinical care despite considerable recent progress in
      our understanding of pathophysiology, resulting in unacceptable levels of
      morbidity and mortality. Major contributors to the disappointing lack of progress
      in paediatric CIPO include a dearth of clarity and uniformity across all aspects
      of clinical care from definition and diagnosis to management. In order to assist
      medical care providers in identifying, evaluating, and managing children with
      CIPO, experts in this condition within the European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition as well as selected external experts,
      were charged with the task of developing a uniform document of evidence- and
      consensus-based recommendations. METHODS: Ten clinically relevant questions
      addressing terminology, diagnostic, therapeutic, and prognostic topics were
      formulated. A systematic literature search was performed from inception to June
      2017 using a number of established electronic databases as well as repositories.
      The approach of the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) was applied to evaluate outcome measures for the research
      questions. Levels of evidence and quality of evidence were assessed using the
      classification system of the Oxford Centre for Evidence-Based Medicine
      (diagnosis) and the GRADE system (treatment). Each of the recommendations were
      discussed, finalized, and voted upon using the nominal voting technique to obtain
      consensus. RESULTS: This evidence- and consensus-based position paper provides
      recommendations specifically for chronic intestinal pseudo-obstruction in infants
      and children. It proposes these be termed paediatric intestinal pseudo
      obstructive (PIPO) disorders to distinguish them from adult onset CIPO. The
      manuscript provides guidance on the diagnosis, evaluation, and treatment of
      children with PIPO in an effort to standardise the quality of clinical care and
      improve short- and long-term outcomes. Key recommendations include the
      development of specific diagnostic criteria for PIPO, red flags to alert
      clinicians to the diagnosis and guidance on the use of available investigative
      modalities. The group advocates early collaboration with expert centres where
      structured diagnosis and management is guided by a multi-disciplinary team, and
      include targeted nutritional, medical, and surgical interventions as well as
      transition to adult services. CONCLUSIONS: This document is intended to be used
      in daily practice from the time of first presentation and definitive diagnosis
      PIPO through to the complex management and treatment interventions such as
      intestinal transplantation. Significant challenges remain to be addressed through
      collaborative clinical and research interactions.

PMID- 29570555
TI  - Single Balloon-assisted Colonoscopy for Placement of Colonic Manometry Catheters:
      Initial Experience in Children.
AB  - OBJECTIVES: Colonic manometry is used frequently in children with long standing
      and difficult to manage constipation to aid in management decisions. Accurate
      analysis requires placement of the colonic manometry catheter in the colon
      without looping. This is technically difficult due to the long-standing nature of
      the constipation in most patients leading to sigmoid and other colonic
      redundancy. Single balloon colonoscopy has been successfully used in adult in
      cases of difficult colonoscopy. We report the first series of single balloon
      assisted colonoscopy for performing difficult colonoscopy in children and placing
      colonic manometry catheters. METHODS: Retrospective chart review was performed to
      identify patients undergoing the procedure. All patients had prior preparation
      with nasogastric golytely. RESULTS: Using the single balloon technique, 36
      patients underwent placement of the colonic manometry catheter (ages ranging from
      3 to 16 years, weights 12 to 95 kg). Catheter placement was successful in all
      cases with procedure times of 20 to 105 minutes. No major complications were
      noted. CONCLUSIONS: This is the first reported series of using single balloon
      assisted colonoscopy to perform difficult colonoscopy in children and place
      colonic manometry catheters. It may have other therapeutic implications in
      children such as removal of polyps or placement of similar catheters.

PMID- 29570556
TI  - Province-wide Biliary Atresia Home Screening Program in British Columbia:
      Evaluation of First 2 Years.
AB  - BACKGROUND AND OBJECTIVES: Biliary atresia (BA), a rare newborn liver disease, is
      the leading cause of liver-related death in children. Early disease recognition
      and timely surgical Kasai hepatoportoenterostomy (KP) offers long-term survival
      without liver transplant. Universal BA screening in Taiwan using infant stool
      color cards (ISCCs) has proven effectiveness. We report our experience with
      infant stool color card (ISCC) BA screening in a province-wide program in British
      Columbia (BC). The objective of this study is to assess program performance and
      cost from launch April 1, 2014 to March 31, 2016. METHODS: ISCCs distributed to
      families upon maternity ward discharge. Parents were instructed to monitor their
      infant's stool color for 1 month and contacted the screening center with
      concerns. The number of live births, ISCC distribution, BA cases, and costs were
      recorded. Cases with Program screen success had both acholic stool recognition
      (ISCC screen success) and timely referral for BA. RESULTS: All 126 maternity
      units received ISCCs. Of 87,583 live births there were 6 BA cases. Of the 5 cases
      with ISCC Screen Success 3 had Program Screen Success. The median KP age in the
      program screen success and failure groups was 49 (42-52) and 116 (49-184) days,
      respectively. Program sensitivity was 50%, specificity 99%, positive predictive
      value 4%, and negative predictive value 99%. A random sample of 1054 charts at BC
      Children's Hospital found an ISCC distribution rate of 94%. After a phase-in
      period, the annual program cost was $30,033.82, and the ISCC cost per birth was
      $0.68. CONCLUSIONS: The screening program has high specificity and distribution
      with low cost. Successful program case identification had earlier age at KP.
      Program modifications aim to improve sensitivity. Longer-term studies will
      determine program impact on health outcomes.

PMID- 29570557
TI  - The Use and Safety of a Novel Haemostatic Spray in the Endoscopic Management of
      Acute Nonvariceal Upper Gastrointestinal Bleeding in Children.
AB  - AIMS AND BACKGROUND: Advanced endohaemostatic technique performance and
      experience is extremely variable in distribution amongst paediatric endoscopists.
      Haemostatic spray (Hemospray), a novel endohaemostatic topically applied powder
      has the advantage of extreme ease of use and; hence may lower the threshold of
      competency required by the endoscopist thereby potentially reducing mortality.
      The aim of the study is to prospectively evaluate the efficacy and the safety of
      haemostatic spray in paediatric patients with acute upper gastrointestinal
      bleeding (AUGIB). METHODS: Prospective enrolment of children with AUGIB (Group 1)
      occurred, either as primary therapy or as an adjunct to standard endohaemostatic
      therapeutic techniques. Patients were assessed for likely need for
      endohaemostatic intervention of >8 of 24 of the paediatric Sheffield AUGIB
      score.A follow-up endoscopy occurred in those deemed to have clinical need pre
      discharge. For comparison, another group (Group 2) of patients, who received
      conventional endohaemostatic treatment in the preceding 36 months, were reviewed.
      RESULTS: A total of 20 applications of Hemospray occurred in 17 patients (8 boys,
      median (range) age: 6.5 years (2 days to 17.75 years) and a total of 29 patients
      were enrolled in Group 2 (16 boys, median [range] age: 5.1 [0.25-17.0]). All
      patients tolerated haemostatic spray applications with no adverse events. The
      haemostatic spray group achieved 100% initial haemostasis with 18% rebleeding
      rate, although only a 6% failure rate after re-application. In the conventional
      group, similar 100% initial haemostasis was achieved with 24% rebleeding rate and
      7% failure rate necessitating surgical interventions. CONCLUSIONS: This
      paediatric series suggests that monotherapy with haemostatic spray is as
      effective as conventional approaches in the management of AUGIB.

PMID- 29570558
TI  - Clinical Remission and Normalization of Laboratory Studies in a Patient With
      Ulcerative Colitis and Primary Sclerosing Cholangitis Using Dietary Therapy.

PMID- 29570559
TI  - The Health Care Transition of Youth With Liver Disease Into the Adult Health
      System: Position Paper From ESPGHAN and EASL.
AB  - BACKGROUND: Medical advances have dramatically improved the long-term prognosis
      of children and adolescents with once-fatal hepatobiliary diseases. However,
      there is no generally accepted optimal pathway of care for the transition from
      paediatric care to the adult health system. AIM: The purpose of this position
      paper is to propose a transition process for young people with paediatric onset
      hepatobiliary diseases from child-centred to adult-centred healthcare services.
      METHODS: Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium,
      France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden,
      Switzerland, and United Kingdom) formulated and answered questions after
      examining the currently published literature on transition from childhood to
      adulthood. PubMed and Google Scholar were systematically searched between 1980
      and January 2018. Quality of evidence was assessed by the Grading of
      Recommendation Assessment, Development and Evaluation (GRADE) system. Expert
      opinions were used to support recommendations whenever the evidence was graded
      weak. All authors voted on each recommendation, using the nominal voting
      technique. RESULTS: We reviewed the literature regarding the optimal timing for
      the initiation of the transition process and the transfer of the patient to adult
      services, principal documents, transition multi-professional team components,
      main barriers, and goals of the general transition process. A transition plan
      based on available evidence was agreed focusing on the individual young people's
      readiness and on coordinated teamwork, with transition monitoring continuing
      until the first year of adult services.We further agreed on selected features of
      transitioning processes inherent to the most frequent paediatric-onset
      hepatobiliary diseases. The discussion highlights specific clinical issues that
      will probably present to adult gastrointestinal specialists and that should be
      considered, according to published evidence, in the long-term tracking of
      patients. CONCLUSIONS: Transfer of medical care of individuals with paediatric
      onset hepatobiliary chronic diseases to adult facilities is a complex task
      requiring multiple involvements of patients and both paediatric and adult care
      providers.

PMID- 29570560
TI  - Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis
      C Infection.
AB  - OBJECTIVES: Dual sofosbuvir/daclatasvir (SOF/DCV) therapy is currently
      recommended by the European Association for Study of Liver (EASL) as an option
      for the treatment of chronic hepatitis C virus (HCV) infection in adults for all
      genotypes; however, it is still not considered for patients younger than 18 years
      old. We aimed to test safety and efficacy of SOF/DCV in adolescent patients 12 to
      17 years old with chronic HCV, genotype 4 infection. METHODS: We conducted a
      prospective, uncontrolled, open-label multicenter study. A total of 30 chronic
      HCV-infected adolescents, aged from 12 to 17 years old were included and treated
      with dual SOF/DCV for 12 weeks. Patients were monitored throughout the treatment
      and follow-up period for safety and efficacy outcome measures including the
      sustained virologic response 12 (SVR12) rate. RESULTS: The intention-to-treat
      (ITT) SVR12 rate was 29 of 30 (96.7%; 95% confidence interval [CI] 83.3%-99.4%).
      The only patient who did not achieve SVR12 was lost to follow-up after showing
      viral negativity at the end of treatment (EOT) visit. Whereas all the remaining
      29 patients (100%, 95% CI 88.3%-100%) who completed the follow-up visits achieved
      SVR12. All patients showed normalized liver enzymes with normal hematological,
      liver and renal function tests at the end of the study. No fatalities or
      treatment-emergent serious or severe adverse events were reported throughout the
      study. CONCLUSIONS: SOF/DCV combined therapy could be a safe and effective
      treatment in adolescent patients 12 to 17 years old with chronic HCV genotype 4
      infection. (See Video, Supplemental Digital Content,
      http://links.lww.com/MPG/B348).

PMID- 29570561
TI  - Changes in an office practice of menopause in the last 25 years.

PMID- 29570562
TI  - An Introduction to the New Journal Forum.

PMID- 29570563
TI  - The Next Generation of Cervical Cancer Screening: Should Guidelines Focus on Best
      Practices for the Future or Current Screening Capacity?

PMID- 29570564
TI  - Low Risk of Cervical Cancer/Precancer Among Most Women Under Surveillance
      Postcolposcopy.
AB  - OBJECTIVE: To inform impending postcolposcopy guidelines, this analysis examined
      the subsequent risk of CIN 3+ among women with a grade lower than CIN 2 (< CIN 2)
      colposcopy results, taking into account the referring results that brought them
      to colposcopy and cotest results postcolposcopy. METHODS: We analyzed 107,005
      women from 25 to 65 years old, recommended for colposcopy at Kaiser Permanente
      Northern California. We estimated absolute risks of CIN 3+ among women: (1)
      recommended for colposcopy (precolposcopy), (2) following colposcopy and with
      histology results < CIN 2 (postcolposcopy), and (3) with cotest results 12 months
      after a < CIN 2 colposcopy (return cotest). RESULTS: After colposcopy showing <
      CIN 2 (n = 69,790; 87% of the women at colposcopy), the 1-year risk of CIN 3+ was
      1.2%, compared with 6.3% at the time of colposcopy recommendation. Negative
      cotest results 1 year after colposcopy identified a large group (37.1%) of women
      whose risk of CIN 3+ (i.e., <0.2% at 3 years after postcolposcopy cotest) was
      comparable with women with normal cytology in the screening population. These
      risks are consistent with current guidelines recommending repeat cotesting 12
      months after colposcopy < CIN 2 and a 3-year return for women with a negative
      postcolposcopy cotest. CONCLUSIONS: Most women are at low risk of subsequent CIN
      3+ after a colposcopy showing < CIN 2, especially those who are human
      papillomavirus-negative postcolposcopy, consistent with current management
      guidelines for repeat testing intervals. Before the finalizing the upcoming
      guidelines, we will consider additional rounds of postcolposcopy cotesting.

PMID- 29570565
TI  - p16 Immunohistochemistry Is Not Always Required For Accurate Diagnosis of Grade 2
      Squamous Intraepithelial Lesions.
AB  - OBJECTIVES: Preinvasive squamous neoplasms of the lower genital tract are
      currently classified using a two-tier system (high- or low-grade squamous
      intraepithelial lesion) as directed by the Lower Anogenital Squamous Terminology
      (LAST) guidelines but may also be subclassified as intraepithelial neoplasia
      grade 1 (-IN1), -IN2, or -IN3. The LAST recommended that all diagnoses of -IN2 be
      supported by immunohistochemistry (IHC) for p16. We examined whether p16 and Ki
      67 IHC are necessary to diagnose -IN2 when the lesion has obvious high-grade
      histology. MATERIALS AND METHODS: p16 and Ki-67 IHC were performed prospectively
      and retrospectively on vulvar, vaginal, and cervical specimens with an initial
      diagnosis of -IN2 based on hematoxylin and eosin morphology, and a final
      diagnosis was made after consensus review. RESULTS: Five of 46 prospective and
      four of 38 retrospective cases were p16 negative. The diagnosis of -IN2 was
      maintained in eight of these nine cases because of compelling high-grade squamous
      intraepithelial lesion histology. Overall, p16 and Ki-67 IHC altered the -IN2
      diagnosis to a lower grade in only one of 84 cases (1.2%, <0.01%-7.1%). Moreover,
      p16 was positive in all cases where the preanalytic impression was of -IN2/3
      (13/13). CONCLUSIONS: p16 IHC lacks utility in cases of morphologically obvious 
      IN2, because the stain is positive in most cases. The LAST recommendation to use
      p16 IHC to support all diagnoses of -IN2 will result in performing the
      immunostain in many circumstances where it is not medically necessary. Among
      cases that are p16 negative, many have compelling high-grade morphology. The LAST
      perspective that the stain trumps histology may allow false-negative IHC results
      to prevail.

PMID- 29570566
TI  - Nerve Growth Factor and Selected Cytokines in Women With and Without Vulvodynia.
AB  - OBJECTIVE: The aim of the study was to assess the association between
      cytokines/neurokines after in vitro stimulation with Candida antigen or
      lipopolysaccharide (LPS) in blood samples among women with and without
      vulvodynia. MATERIALS AND METHODS: Women with vulvodynia and asymptomatic
      controls at three offices at the University of Michigan were examined clinically
      and completed a comprehensive survey in this cross-sectional study.
      Cytokine/neurokine levels were determined on blood samples using established
      ELISA protocols. Analysis of 48 cases and 42 ethnically matched controls included
      descriptive statistics (median, minimal, and maximal levels of
      cytokines/neurokines), overall and in cases and controls. Because of left
      censored measurements, interval censored survival analysis was used to assess the
      association between case/control status and pain characteristics with
      cytokine/neurokine levels. RESULTS: Participants ranged in age from 19 to 60
      years. Levels of IL1beta, IL1-RA, TNFalpha, IL-6, and IL-8 increased
      substantially after LPS stimulation, whereas no response was seen on IFNgamma or
      nerve growth factor (NGF). Each increased after Candida antigen stimulation,
      although responses to Candida antigen stimulation of IL1beta, IL-6, and TNFalpha
      were less robust than after LPS. Only NGF was significantly increased in
      vulvodynia cases compared with controls (Exp beta (95% CI) = 2.08 [1.08-3.98])
      after 24-hour Candida antigen stimulation and persisted when controlled for age,
      use of oral contraceptives, or history of Candida vulvovaginitis. No association
      between cytokine/neurokine levels and pain characteristics was found.
      CONCLUSIONS: Compared with that of control women, whole blood from women with
      vulvodynia demonstrates an enhanced production of NGF, but not of a set of
      inflammation-related cytokines, in response to Candida antigen stimulation.

PMID- 29570567
TI  - Use and Nondisclosure of Complementary Health Approaches Among US Children with
      Developmental Disabilities.
AB  - OBJECTIVES: Many US children use complementary health approaches (CHAs),
      including some modalities that may be ineffective, unsafe, and/or costly. Yet,
      little is known about the prevalence and correlates of CHA use among children
      with developmental disabilities (DDs), as well as parent nondisclosure of CHAs
      used for children with DDs to health care providers. We, therefore, aimed to
      profile the use and nondisclosure of CHAs among US children with DDs. METHODS: We
      analyzed data from the 2012 National Health Interview Survey, which included the
      most recent Child Complementary and Alternative Medicine Supplement. The study
      sample was comprised of 2141 children with DDs aged 4 to 17 years. RESULTS:
      Nearly one-quarter (23%) of US children with DDs used CHAs. Among those with a
      personal health provider, 42% of parents did not disclose some or all CHAs used
      to the child's provider. The adjusted odds ratios of using CHAs were greater
      among those with female sex, higher household income, residences not in the
      South, difficulty accessing care, or comorbid conditions. CHA was most commonly
      used because "it is natural." Nondisclosure was associated with female sex, older
      age, having no functional limitations, less conventional services use, and use of
      fewer CHAs. The most common reason for nondisclosure was that the child's
      provider did not ask. CONCLUSION: Complementary health approach use is prevalent
      among US children with DDs, and nondisclosure is likely among those who use CHAs.
      Future intervention targeting education and communication about CHAs for parents
      of children with DDs and their health care providers may promote disclosure.

PMID- 29570568
TI  - Perceived Toddler Sleep Problems, Co-sleeping, and Maternal Sleep and Mental
      Health.
AB  - OBJECTIVE: Childhood sleep problems are associated with insufficient parental
      sleep and adverse maternal mental health symptoms, which may be exacerbated when
      mothers/toddlers co-sleep (i.e., bed/room sharing). This study examines maternal
      sleep duration as a mechanism linking perceived toddler sleep problems with
      maternal mental health and examines whether these associations vary by co
      sleeping, in addition to exploring alternative models. METHODS: Low-income
      mothers of toddlers (n = 280) (age 12-32 months) recruited from Women, Infants,
      and Children and pediatric clinics provided demographic information and completed
      questionnaires on their toddler's sleep and their own sleep duration and mental
      health symptoms (depressive symptoms, anxiety, and stress). Indirect and
      conditional indirect models were conducted to examine the relation between
      perceived toddler sleep problems and maternal mental health. RESULTS: Perceived
      toddler sleep problems were associated with an average decrease of 51 minutes in
      maternal sleep when co-sleeping (mean = 6.1 h). Maternal sleep duration mediated
      the relation between perceived toddler sleep problems and maternal symptoms of
      depression, anxiety, and stress for co-sleeping mothers. Maternal sleep duration
      did not mediate relations between maternal mental health symptoms and perceived
      toddler sleep problems. CONCLUSION: This study provides a conceptual model by
      which parent and child sleep is related to parental mental health. Practitioners
      might consider alternatives to co-sleeping when discussing sleep arrangements
      with parents. Future studies should replicate results longitudinally and examine
      whether reducing co-sleeping improves maternal sleep duration and reduces
      perceptions of toddler sleep problems.

PMID- 29570569
TI  - Sensitivity and Specificity of 2 Autism Screeners Among Referred Children Between
      16 and 48 Months of Age.
AB  - OBJECTIVE: Autism screening is recommended by the American Academy of Pediatrics
      and the Centers for Disease Control and Prevention at ages 18 and 24 months.
      Popular screening tests have been validated for the age range of 16 to 30 months.
      However, only a minority of children with autism spectrum disorder (ASD) are
      identified by age 3 years, and many are not identified until after they enter
      school. Thus, we aimed to measure the sensitivity and specificity of 2 available
      screening tests for ASDs in children older than 30 months. METHODS: We assessed
      the sensitivity and specificity of 2 ASD screening tools administered to parents
      of children who were referred to a developmental clinic between the ages of 16
      and 48 months: the Modified Checklist for Autism in Toddlers (M-CHAT) and the
      Parent's Observations of Social Interactions (POSI), which is a component of a
      comprehensive screening instrument called, the Survey of Well-being of Young
      Children. RESULTS: Both the M-CHAT and the POSI had acceptable sensitivity
      (>=75%) among children across the age range studied. Their specificity was
      limited by the fact that the study was conducted in a developmental referral
      clinic. CONCLUSION: Two readily available screening tools, the POSI and the M
      CHAT, have acceptable sensitivity in evaluating risk for autism in children at
      least to age 48 months. Further research should investigate their sensitivity and
      specificity when used in primary care settings.

PMID- 29570571
TI  - Cardiac Autonomic and Blood Pressure Responses to an Acute Foam Rolling Session.
AB  - Lastova, K, Nordvall, M, Walters-Edwards, M, Allnutt, A, and Wong, A. Cardiac
      autonomic and blood pressure responses to an acute foam rolling session. J
      Strength Cond Res 32(10): 2825-2830, 2018-Foam rolling (FR) is a self-myofascial
      release method that has become extremely popular among athletes and fitness
      enthusiasts for its ability to improve flexibility and range of motion and
      alleviate delayed-onset muscle soreness. However, the cardiac autonomic
      modulation and blood pressure (BP) responses induced by an acute FR session are
      currently unknown. This study evaluated the effects of an acute session of FR
      exercise on heart rate variability (HRV) and BP responses in healthy individuals.
      Fifteen (M = 8, F = 7) healthy subjects completed either an FR or nonexercise
      control trial in randomized order. Heart rate variability and BP measurements
      were collected at baseline, 10, and 30 minutes after each trial. There were
      significant increases (p < 0.01) in markers of vagal tone (normalized high
      frequency) for 30 minutes after the FR trial, whereas no changes from baseline
      were observed after control. There were also significant decreases (p < 0.05) in
      markers of sympathetic activity (normalized low frequency), sympathovagal balance
      (ratio of normalized low frequency to normalized high frequency), systolic BP,
      and diastolic BP at 10 and 30 minutes after the trial KB trial, whereas no
      changes from baseline were observed after the control trial. Our findings
      indicate that FR decreases sympathovagal balance for 30 minutes postintervention,
      which is concurrent with an important hypotensive effect. Further research is
      warranted to evaluate the potential cardiovascular protective effects of FR in
      diverse populations.

PMID- 29570572
TI  - Are Change-of-Direction Speed and Reactive Agility Independent Skills Even When
      Using the Same Movement Pattern?
AB  - Coh, M, Vodicar, J, Zvan, M, Simenko, J, Stodolka, J, Rauter, S, and Mackala, K.
      Are change-of-direction speed and reactive agility independent skills even when
      using the same movement pattern? J Strength Cond Res 32(7): 1929-1936, 2018-The
      purpose of this investigation was to determine whether there are differences
      between the 2 approaches to quantifying agility (preplanned vs. unplanned
      response) when reacting to a stimulus in an identical spatial scenarios. The
      study involved 45 male and 31 female trained athletes (age 21.2 +/- 1.78 and 20.6
      +/- 1.27 years, body height 181.6 +/- 8.31 and 167.7 +/- 5.03 cm, and body mass
      78.9 +/- 11.33 and 63.3 +/- 8.65 kg, respectively). A light-based reactive
      training system was used to measure the time to completion in a task that
      assessed agility by change-of-direction speed (CODS) in a preplanned condition
      and reactive agility (RA) in an unplanned condition across 4 spatial
      configurations. Sprint performance in a 30-m sprint and lower limb reactive power
      in a 10-m single leg jump test was also measured. Significant differences (p <=
      0.05) were found between men and women in all tests and between performance in
      the CODS and RA condition for each spatial configuration. Significant
      correlations were observed between 30-m starting sprint speed and CODS and RA
      performance measured in a semicircle (r = 0.62, r = 0.60) and lateral (r = 0.54,
      r = 0.58) configuration in male athletes. The present findings suggest that CODS
      and RA are 2 different and independent skill domains that define agility. These
      qualities should be diagnosed by discrete assessments and enhanced by different
      training methodologies.

PMID- 29570573
TI  - Sexual Dimorphism in the Estimation of Upper-Limb Blood Flow Restriction in the
      Seated Position.
AB  - Borges, A, Teodosio, C, Matos, P, Mil-Homens, P, Pezarat-Correia, P, Fahs, C, and
      Mendonca, GV. Sexual dimorphism in the estimation of upper-limb blood flow
      restriction in the seated position. J Strength Cond Res 32(7): 2096-2102, 2018
      Arterial occlusion pressure (AOP) is typically used to normalize blood flow
      restriction (BFR) during low-intensity BFR exercise. Despite strong evidence for
      sexual dimorphism in muscle blood flow, sex-related differences in AOP estimation
      remain a controversial topic. We aimed at determining whether the relationship of
      upper-limb AOP with arm circumference and systolic blood pressure (BP) differs
      between men and women resting in the seated position. Sixty-two healthy young
      participants (31 men: 21.7 +/- 2.3; 31 women: 22.0 +/- 2.0 years) were included
      in this study. Arm circumference, resting BP, and AOP were taken in the seated
      position. Multiple linear regression analysis was used to determine whether the
      relationship of AOP with arm circumference and resting BP differed between sexes.
      Prediction accuracy was assessed with the mean absolute percent error and Bland
      Altman plots. Men had higher systolic BP and larger arm circumference than women
      (p < 0.05). Nevertheless, AOP was similar between sexes. Arm circumference,
      systolic BP, and sex were all significant predictors of AOP (p < 0.05),
      explaining 42% of its variance. The absolute percent error was similar in both
      sexes (men: -0.55 +/- 7.12; women: -0.39 +/- 6.31%, p > 0.05). Bland-Altman plots
      showed that the mean difference between actual and estimated AOP was nearly zero
      in both groups, with no systematic overestimation or underestimation. In
      conclusion, arm circumference, systolic BP, and sex are all significant
      predictors of upper-limb-seated AOP. Their measurement allows for the indirect
      estimation of BFR pressure within the context of exercise training.

PMID- 29570574
TI  - Sequencing Effects of Plyometric Training Applied Before or After Regular Soccer
      Training on Measures of Physical Fitness in Young Players.
AB  - To compare the effects of short-term (i.e., 7 week) plyometric training applied
      before (PJT-B) or after (PJT-A) soccer practice on components of physical fitness
      in young soccer players, a single-blind randomized controlled trial was
      conducted. Post-pubertal boys aged 17.0+/-0.5 years were allocated to three
      groups: PJT-B (n=12), PJT-A (n=14), and control (CON; n=12). The outcome measures
      included tests to evaluate 20-m speed, standing long jump [SLJ], squat jump [SJ],
      countermovement jump [CMJ], and drop jump [DJ], 20-m multistage shuttle running
      speed [MSSRT], and Illinois change of direction speed [ICODT]. While the CON
      performed soccer-specific training, the PJT-A and PJT-B groups conducted the same
      soccer-specific sessions but replaced ~11% of their time with plyometric
      training. The PJT-B group performed plyometric exercises after a warm-up program,
      and the PJT-A group conducted plyometric exercises ~10 minutes after the
      completion of soccer training. Analyses of variance (ANOVAs) were used to detect
      differences between groups in all variables for pre- and post-training tests.
      Main effects of time (all p<.01; d=0.19-0.79) and group x time interactions (all
      p<.05; d=0.17-0.76) were observed for all examined variables. Post hoc analyses
      revealed significant increases in the PJT-B group (SLJ: 9.4%, d=1.7; CMJ: 11.2%,
      d=0.75; 20-m MSSRT: 9.0%, d=0.77) and the PJT-A group (SLJ: 3.1%, d=0.7; CMJ:
      4.9%, d=0.27; 20-m MSSRT: 9.0%, d=0.76). Post hoc analyses also revealed
      significant increases in the PJT-B group (20-m speed: -7.4%, d=0.75; 20-cm DJ
      reactive strength index: 19.1%, d=1.4; SJ: 6.3%, d=0.44; ICODT results: -4.2%,
      d=1.1). In general, our study revealed that plyometric training is effective in
      improving measures of physical fitness in young male soccer players when combined
      with regular soccer training. More specifically, larger training induced effects
      on physical fitness were registered if plyometric training was conducted prior to
      soccer specific training.

PMID- 29570575
TI  - Evaluation of the Most Reliable Procedure of Determining Jump Height During the
      Loaded Countermovement Jump Exercise: Take-Off Velocity vs. Flight Time.
AB  - Perez-Castilla, A and Garcia-Ramos, A. Evaluation of the most reliable procedure
      of determining jump height during the loaded countermovement jump exercise: Take
      off velocity vs. flight time. J Strength Cond Res 32(7): 2025-2030, 2018-This
      study aimed to compare the reliability of jump height between the 2 standard
      procedures of analyzing force-time data (take-off velocity [TOV] and flight time
      [FT]) during the loaded countermovement (CMJ) exercise performed with a free
      weight barbell and in a Smith machine. The jump height of 17 men (age: 22.2 +/-
      2.2 years, body mass: 75.2 +/- 7.1 kg, and height: 177.0 +/- 6.0 cm) was tested
      in 4 sessions (twice for each CMJ type) against external loads of 17, 30, 45, 60,
      and 75 kg. Jump height reliability was comparable between the TOV (coefficient of
      variation [CV]: 6.42 +/- 2.41%) and FT (CV: 6.53 +/- 2.17%) during the free
      weight CMJ, but it was higher for the FT when the CMJ was performed in a Smith
      machine (CV: 11.34 +/- 3.73% for TOV and 5.95 +/- 1.12% for FT). Bland-Altman
      plots revealed trivial differences (<=0.27 cm) and no heteroscedasticity of the
      errors (R <= 0.09) for the jump height obtained by the TOV and FT procedures,
      whereas the random error between both procedures was higher for the CMJ performed
      in the Smith machine (2.02 cm) compared with the free-weight barbell (1.26 cm).
      Based on these results, we recommend the FT procedure to determine jump height
      during the loaded CMJ performed in a Smith machine, whereas the TOV and FT
      procedures provide similar reliability during the free-weight CMJ.

PMID- 29570576
TI  - Effect of Match Factors on the Running Performance of Elite Female Soccer
      Players.
AB  - Trewin, J, Meylan, C, Varley, MC, Cronin, J, and Ling, D. Effect of match factors
      on the running performance of elite female soccer players. J Strength Cond Res
      32(7): 2002-2009, 2018-The purpose of this study was to examine the effects of
      match factors on the match running of elite female soccer players. Players from
      the same women's national team (n = 45) were monitored during 47 international
      fixtures (files = 606) across 4 years (2012-2015) using 10-Hz global positioning
      system devices. A mixed model was used to analyze the effects of altitude,
      temperature, match outcome, opposition ranking, and congested schedules. At
      altitude (>500 m), a small increase in the number of accelerations (effect size
      [ES] = 0.40) and a small decrease in total distance (ES = -0.54) were observed,
      whereas at higher temperatures, there were decreases in all metrics (ES = -0.83
      to -0.16). Playing a lower ranked team in a draw resulted in a moderate increase
      in high-speed running (ES = 0.89), with small to moderate decreases in total
      distance and low-speed running noted in a loss or a win. Winning against higher
      ranked opponents indicated moderately higher total distance and low-speed running
      (ES = 0.75), compared with a draw. Although the number of accelerations were
      higher in a draw against lower ranked opponents, compared with a win and a loss
      (ES = 0.95 and 0.89, respectively). Practitioners should consider the effect of
      match factors on match running in elite female soccer.

PMID- 29570577
TI  - Lower Extremity Horizontal Work But Not Vertical Power Predicts Lower Extremity
      Injury in Female Collegiate Dancers.
AB  - Ambegaonkar, JP, Schock, CS, Caswell, SV, Cortes, N, Hansen-Honeycutt, J, and
      Wyon, MA. Lower extremity horizontal work but not vertical power predicts lower
      extremity injury in female collegiate dancers. J Strength Cond Res 32(7): 2018
      2024, 2018-Dancers often perform powerful and explosive movements that require
      adequate lower extremity (LE) activity in horizontal and vertical directions. We
      examined whether these measures were interrelated and whether they predicted LE
      injury status in dancers using binary logistic regressions and receiver operator
      characteristic (ROC) curve analyses. Forty-three collegiate female dancers (18 +/
      0.7 years; 162.6 +/- 5.9 cm; 59.4 +/- 7.1 kg) performed single leg hop (SLH, m)
      and vertical jump (VJ, cm) tests. Single leg hop and VJ distances were used to
      calculate SLH norm (as a % of body height) and vertical power (vPower, watts).
      Lower extremity injuries and dance exposure hours (DEhrs) were recorded for 16
      weeks. Dancers had 51 injuries resulting in a 3.7/1,000 DEhr injury incidence
      rate (95% confidence interval [CI]: 2.7-4.7). Twenty dancers were injured,
      whereas 23 remained injury free. Injured dancers had significantly lower SLH norm
      than noninjured dancers (t = 2.7, p = 0.009, 85.2 +/- 11.2% vs. 76.8 +/- 8.4%,
      respectively), but vPower was similar (t = 0.6, p = 0.53, injured = 2,632.0 +/-
      442.9 watts, noninjured = 2,722.7 +/- 480.0 watts). SLH norm, but not vPower
      significantly predicted injury status chi(1,43) = 5.9, p = 0.02. Specifically, an
      SLH norm cut-off value of 78.2% identified dancers at injury risk (area under the
      curve = 0.73, SE = 0.08, p = 0.01, 95% CI = 0.57-0.89, sensitivity = 0.75,
      specificity = 0.70). However, vPower was not able to identify dancers at risk (p
      = 0.36). vPower had moderate relationships with SLH norm (r = 0.31, p = 0.04).
      Compared with injured dancers, noninjured dancers had greater SLH norm but
      similar vPower. Only SLH norm predicted injury status in female collegiate
      dancers. Thus, the SLH test may possibly predict LE injury risk in dancers.
      Strength and conditioning coaches can prospectively use baseline SLH test
      screenings to identify dancers whose SLH is less than 78.2% of their height
      because these dancers may have increased probability of LE injury risk. Coaches
      can then include horizontal direction exercises when designing training programs
      and examine whether these programs reduce LE injury risk in female collegiate
      dancers.

PMID- 29570578
TI  - Evaluation of Seasonal Changes in Fitness, Anthropometrics, and Body Composition
      in Collegiate Division II Female Soccer Players.
AB  - Peart, AN, Nicks, CR, Mangum, M, and Tyo, BM. Evaluation of seasonal changes in
      fitness, anthropometrics, and body composition in collegiate division II female
      soccer players. J Strength Cond Res 32(7): 2010-2017, 2018-The purpose of this
      study was to investigate anthropometrics, body composition, aerobic and anaerobic
      fitness of collegiate Division II female soccer players throughout a calendar
      year. Eighteen (20 +/- 0.9 years) National Collegiate Athletics Association
      division II female soccer players from the same team participated in the study.
      Anthropometrics and body composition variables were assessed in addition to the
      counter movement jump (CMJ), Wingate Anaerobic Test (WAT), and peak oxygen uptake
      (V[Combining Dot Above]O2peak). Data were collected over 5 time points: end of
      competitive seasons (ECS1 and ECS2), beginning of off-season (BOS), end of off
      season (EOS), and preseason (PS). Repeated-measures analysis of variance was
      conducted to compare test scores among all 5 data collection points. Where
      appropriate, Bonferroni post hoc tests were used to determine which points were
      significantly different. Hip circumference decreased significantly (p < 0.001)
      from EOS (98.47 +/- 6.5 cm) to PS (94.46 +/- 6.8 cm). Fat mass (12.73 +/- 5.4 kg)
      was significantly different in ECS2 compared with BOS and EOS means (p <= 0.05)
      and percentage of body fat (%BF) (20.08 +/- 5.44) significantly different in ECS2
      compared with ECS1, BOS, and EOS means (p <= 0.05), whereas fat-free mass (FFM)
      was maintained from ECS1 to ECS2. Counter movement jump, WAT, and V[Combining Dot
      Above]O2peak performance did not significantly change from ECS1 to ECS2.
      Anthropometrics and body composition results are similar to previous studies
      measuring Division II to professional female soccer players. Counter movement
      jump results remained consistent and are comparable to results on Division I
      female soccer players. Coaches and researchers can use these data to help design
      and evaluate training programs throughout a calendar year.

PMID- 29570579
TI  - Moderate Load Resisted Sprints do Not Improve Subsequent Sprint Performance in
      Varsity Level Sprinters.
AB  - Resisted sprint training (RST) is commonly used for performance enhancement in
      athletics and team sports to develop acceleration ability. Evidence suggests that
      RST may be effective as a short-term intervention to improve successive sprints.
      While these improvements have been measured in team sport athletes, limited
      research has considered the acute effects of RST training in sprint-trained
      athletes. Therefore, the aim of the current study was to determine if performing
      RST with varsity level sprinters using sled-equivalent resistive loads of ~45%
      body mass results in a potentiation effect, leading to improvements in subsequent
      maximal sprint performance over 0-5 m and 0-20 m. Competitive sprinters (n=20),
      were randomly assigned to perform a pre/post maximal 20 m sprint separated by
      either 3 resisted (RST group) or un-resisted (URS group) sprints. The RST or URS
      protocol was performed on four occasions separated by at least 7 days. No
      significant differences were observed between the RST and URS groups comparing
      changes in sprint times over 0-5 m (URS Delta = <0.01 s +/- 0.03 s, RST Delta =
      <0.01 s +/- 0.03 s) and 0-20 m (URS Delta = 0.013 s +/- 0.04 s, RST Delta = <0.01
      s +/- 0.04 s). We conclude that resisted sprints using sled equivalent loads of
      45% body mass are ineffective at inducing a potentiating effect on subsequent
      sprint performance in varsity level sprinters. In this population of trained
      athletes, greater loads may be necessary to induce a potentiating effect.

PMID- 29570580
TI  - Effects of Exercise Induced Muscle Damage in Well-Trained Cyclists' Aerobic and
      Anaerobic Performance.
AB  - This study purpose was to analyze the effect of EIMD in gross efficiency and in
      aerobic and anaerobic cycling performance. Nine well-trained cyclists (30.8 +/-
      6.4 years, cycling experience 8.4 +/- 5.6 years) visited the laboratory 5 times.
      During the first visit, they performed a maximal incremental test on a cycle
      ergometer, to identify VO2max (55.2 +/- 4.9 mL.kg.min) and maximum aerobic power
      (Pmax; 327.0 +/- 28.5 watts). During the second visit (control), they cycled 5
      minutes at 60% of Pmax, 5 minutes at 70% of Pmax, 5 minutes time-trial, and
      Wingate test. During the third visit, the athletes performed 10 sets of 10
      counter-movement jumps, to generate EIMD. The athletes repeated the second visit
      tests (control) 30 minutes, 48h (fourth visit) and 96h (fifth visit) after the
      jumps. The RPE values increased 48h after EIMD (3.8 vs. 3.1) at 60% of Pmax. The
      ventilation and RER increased at 60% of Pmax (up to 4.3 L.min and 0.04,
      respectively) and at 70% of Pmax (up to 5.4 L.min and 0.05, respectively), mainly
      after 96h. There was no significant difference in VO2, VCO2, and HR in sub
      maximal exercises, neither in time-trial. No differences were observed in the
      Wingate tests. In conclusion, the EIMD didn't impair gross efficiency, nor
      aerobic and anaerobic performances in trained cyclists. However, despite the
      benefits of strength training to improve cyclists' performance, coaches must be
      cautious to the days after the strength training sessions, because EIMD may
      change the perception of maintaining a given submaximal intensity during training
      or competition.

PMID- 29570581
TI  - INTRAVITREAL GAS INJECTION WITH LASER PHOTOCOAGULATION FOR HIGHLY MYOPIC
      FOVEOSCHISIS: Technique and Outcome.
AB  - PURPOSE: To evaluate the effects of gas tamponade combined with laser
      photocoagulation without vitrectomy in patients with highly myopic foveoschisis.
      METHODS: This retrospective noncomparative case series included 30 eyes of 23
      patients with highly myopic foveoschisis who were treated by intravitreal
      injection of 0.5 to 0.7 mL C3F8 combined with laser photocoagulation 1 week
      later, and remained in the face-down position for 3 weeks. The patients were
      followed up for at least 6 months after the treatment. The refractive status,
      best-corrected visual acuity, and anatomical parameters of retina observed with
      the optical coherence tomography before and after the treatment were recorded.
      RESULTS: The mean age of the 23 patients (6 men and 17 women) was 50.4 +/- 15.1
      years. The average follow-up duration was 20.8 +/- 20.6 months. At the final
      follow-up, 23 eyes (76.7%) completely (17 eyes) or partially (6 eyes) resolved.
      Seventeen eyes had complete data of optical coherence tomography parameters, the
      mean central foveal thickness decreased significantly from 505.24 +/- 466.22 MUm
      to 186.41 +/- 95.36 MUm (P = 0.01), and the mean maximal macular thickness from
      687.88 +/- 397.00 MUm to 313.65 +/- 83.07 MUm (P = 0.001). The mean final
      logarithm of the minimum angle of resolution best-corrected visual acuity
      (Snellen equivalent) of the 30 eyes ranged from 1.6 (20/800) to 0.2 (20/32),
      showing a slight improvement from 0.91 +/- 0.44 (20/163) preoperatively to 0.90
      +/- 0.39 (20/160) postoperatively (P = 0.87). CONCLUSION: C3F8 tamponade combined
      with laser photocoagulation could be an alternative treatment for highly myopic
      foveoschisis.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- 29570582
TI  - Optical Coherence Tomography in Subconjunctival Silicone Oil.

PMID- 29570583
TI  - Antibiotic Recommendations for Acute Otitis Media and Acute Bacterial Sinusitis:
      Conundrum No More.
AB  - There has been a substantial change in the prevalence and microbiologic
      characteristics of cases of acute otitis media secondary to the widespread use of
      pneumococcal conjugate vaccines. Current trends in nasopharyngeal colonization
      and the microbiology of acute otitis media support a change in the recommendation
      for antibiotic management of acute otitis media and acute bacterial sinusitis in
      children.

PMID- 29570584
TI  - First Case of Bacteremia Caused by Kytococcus schroeteri in a Child With
      Congenital Adrenal Hyperplasia.
AB  - Kytococcus schroeteri is a commensal organism of the human skin, which may cause
      serious infections in immunocompromised patients. We report the first case of K.
      schroeteri bacteremia in a child with congenital adrenal hyperplasia, identified
      by matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (Bruker Daltonics, Germany). Identification was confirmed by 16S rRNA gene
      sequencing.

PMID- 29570585
TI  - Probiotics for Modification of the Incidence or Severity of Respiratory Tract
      Infections.

PMID- 29570586
TI  - Hospitalization Rate and Population-based Incidence of Hospitalization for
      Community-acquired Pneumonia Among Children in Suzhou, China.
AB  - BACKGROUND: Data on hospitalization burden of community-acquired pneumonia (CAP)
      in children are very limited in China. This study aimed to estimate the
      hospitalization rate (HR) and population-based incidence of hospitalization of
      CAP for children <15 years of age in Suzhou, China. METHODS: This was a
      retrospective study of children hospitalized in Soochow University Affiliated
      Children's Hospital from January 2010 to December 2014. Children who were
      residents of downtown Suzhou, 29 days to <15 years of age, with discharge
      diagnosis codes (International Classification of Diseases, 10th revision)
      including J09-J18 and J20-J22 were included. All-cause clinical community
      acquired pneumonia (CCAP) and radiographically confirmed pneumonia (RCAP) were
      identified based on individual medical chart review. The HR and population-based
      cumulative incidence of hospitalization (HI) were calculated. RESULTS: Among
      184,734 children <15 years of age admitted to Soochow University Affiliated
      Children's Hospital during the study period, 31,302 children were identified as
      having CCAP and 24,218 (77.4%) children confirmed as having RCAP. CCAP
      hospitalization occurred year round and peaked during winter and early spring.
      The overall HRs for CCAP and RCAP were 189.0 [95% confidence interval (CI): 187.1
      190.9] and 146.2 (95% CI: 144-148) per 1000 hospitalizations, respectively, and
      the HIs per 100,000 children annually were CCAP, 3235.8 (95% CI: 3207.3-3264.2)
      and RCAP, 2503.5 (95% CI: 2478.3-2528.6). For children <5 years of age, the HR
      for CCAP was 248.4 (95% CI: 245.9-250.9) and RCAP was 194.0 (95% CI: 191.4-196.3)
      per 1000 hospitalizations; the HI for CCAP was 6956.2 (95% CI: 6892.8-7019.6) and
      5431.9 (95% CI: 5375.4-5488.4) per 100,000 children for RCAP. The highest HR and
      HI were observed in children 29 days to <6 months of age: HR for CCAP was 407.4
      (95% CI: 400.9-413.9) per 1000 hospitalizations and HI for CCAP was 11,203.7 (95%
      CI: 11,026.8-11,380.6) per 100,000 children annually. CONCLUSIONS: There is a
      considerable burden of CAP among children <15 years of age in Suzhou,
      particularly among children 29 days to <6 months of age and during winter and
      early spring. These data provide valuable information to monitor CAP trends over
      time in children of Suzhou, China.

PMID- 29570587
TI  - Invasive Gastrointestinal Mucormycosis: A Master Masquerader.
AB  - We report 3 previously healthy children of postneonatal age who developed fatal
      form of gastrointestinal mucormycosis after systemic inflammatory response
      syndrome, shock and metabolic acidosis. Abdominal distension and peritonitis were
      secondary complications. The study highlights the importance of clinical
      suspicion of gastrointestinal mucormycosis when the triad of shock requiring
      vasoactive drugs, metabolic acidosis and abdominal distension is present.

PMID- 29570588
TI  - HLA-DR Expression on Monocyte Subsets in Critically Ill Children.
AB  - BACKGROUND: To longitudinally study blood monocyte subset distribution and human
      leukocyte antigen-DR (HLA-DR) expression on monocyte subsets in children with
      sepsis, post-surgery and trauma in relation to nosocomial infections and
      mortality. METHODS: In 37 healthy children and 37 critically ill children (12
      sepsis, 11 post-surgery, 10 trauma and 4 admitted for other reasons)
      participating in a randomized controlled trial on early versus late initiation of
      parenteral nutrition-monocyte subset distribution and HLA-DR expression on
      monocyte subsets were measured by flow cytometry upon admission and on days 2, 3
      and 4 of pediatric intensive care unit (PICU) stay. RESULTS: Upon PICU admission,
      critically ill children had a higher proportion of classical monocytes
      (CD14++CD16-) than healthy children [PICU 95% (interquartile range [IQR] 88%
      98%); controls, 87% (IQR 85%-90%), P < 0.001]. HLA-DR expression was
      significantly decreased within all monocyte subsets and at all time points, being
      most manifest on classical monocytes and in patients with sepsis. Percentage of
      HLA-DR expressing classical monocytes [upon PICU admission 67% (IQR 44%-88%);
      controls 95% (IQR 92%-98%), P < 0.001], as well as the HLA-DR mean fluorescence
      intensity [upon PICU admission 3219 (IQR 2650-4211); controls 6545 (IQR 5558
      7647), P < 0.001], decreased during PICU stay. Patients who developed nosocomial
      infections (n = 13) or who died (n = 6) had lower HLA-DR expression on classical
      monocytes at day 2 (P = 0.002) and day 3 (P = 0.04), respectively. CONCLUSIONS:
      Monocytic HLA-DR expression decreased during PICU stay and was lower compared
      with controls on all examined time points, especially on classical monocytes and
      in children admitted for sepsis. Low HLA-DR expression on classical monocytes was
      associated with nosocomial infections and death.

PMID- 29570589
TI  - Re-emergence of Congenital Syphilis in Ohio.
AB  - BACKGROUND: The recent occurrence of congenital syphilis in Columbus, OH, raised
      concern for an increase in syphilis among women and infants. The objectives were
      to examine the rates of syphilis among men, women and infants in Ohio from 2003
      to 2016 and compare these rates to the rest of the United States. METHODS: This
      retrospective study evaluated cases of syphilis among men, women and infants from
      2003 to 2016 using data from the Ohio Department of Health and the Centers for
      Disease Control and Prevention. RESULTS: In Ohio from 2003 to 2016, the number of
      all syphilis cases among women significantly increased from 153 (2.6/100,000) to
      294 (5.2/100,000), respectively (b = 0.26; P = 0.001; 95% confidence interval
      [CI]: 0.137-0.382). From 2003 to 2016, congenital syphilis in Ohio also increased
      significantly from 3 (2/100,000) to 13 cases (9.3/100,000), respectively (b =
      1.05; P <= 0.001; 95% CI: 0.687-1.408). The increase in congenital syphilis
      mirrored the increase in all cases of syphilis in women but not with the rates of
      primary and secondary syphilis. Among men, cases of primary and secondary
      syphilis increased significantly in Ohio and the rest of the United States, from
      156 (2.8/100,000) and 5956 (4.2/100,000) in 2003 to 622 (10.5/100,000) and 24,724
      (15.6/100,000) in 2016, respectively (Ohio: b = 0.55; P < 0.001; 95% CI: 0.426
      0.679; United States: b = 0.77; P < 0.001; 95% CI: 0.629-0.916). CONCLUSIONS: The
      association of congenital syphilis with all syphilis cases in women highlights
      the importance of reporting all cases and not just primary and secondary
      syphilis. The increase in congenital syphilis reinforces the recommendation for
      repeat maternal screening during pregnancy.

PMID- 29570590
TI  - Osteoarticular Infections Following Open or Penetrating Trauma in Children in the
      Post-Community-Acquired Methicillin-resistant Staphylococcus aureus Era: The
      Impact of Enterobacter cloacae.
AB  - BACKGROUND: Most cases of pediatric osteoarticular infections (OAIs) are
      hematogenous in nature and caused by Staphylococcus aureus. OAI in children can
      also occur through direct inoculation of microorganisms secondary to penetrating
      or open trauma. No studies in the United States have evaluated the microbiology
      or outcomes of trauma-related OAI (TROAI) in children in the era of community
      acquired methicillin-resistant S. aureus (CA-MRSA). METHODS: Cases were
      identified from the inpatient infectious diseases consultation database at Texas
      Children's Hospital from January 2011 to December 2016. TROAI cases were those in
      which OAI developed following a clear history of penetrating trauma, open
      fracture, crush injury or traumatic amputation. Only cases with radiographic
      evidence of bone abscess, gross appearance of infection at the time of surgery
      and/or positive cultures from bone or joint were included. Complications included
      recurrence of infection, pathologic fracture or chronic osteomyelitis. RESULTS:
      During the study period, 692 consultations for OAI were performed, with 34
      meeting inclusion criteria. In 68%, at least 1 organism was isolated, and the
      most commonly isolated organisms were S. aureus (32% overall, 21% MRSA) and
      Enterobacter cloacae (24%). Polymicrobial infections occurred in 38% of patients.
      Eighty-five percentage of patients had at least 1 surgical procedure, and 38%
      underwent >= 2 procedures. Eighty-two percentage of patients were discharged on
      oral therapy. Complications developed in 15% of patients and were more commonly
      associated with E. cloacae (80% vs. 14%, P = 0.007) and fungi (P = 0.03).
      CONCLUSION: TROAI are relatively uncommon in children but cause significant
      morbidity. While MRSA contributes substantially to TROAI, the highly diverse
      microbiology emphasizes the importance of obtaining cultures for microbiologic
      diagnosis and management. Clinicians should be aware of the frequency of E.
      cloacae in TROAI and its high risk for sequelae.

PMID- 29570591
TI  - Emergence of Nontuberculous Mycobacterial Lymphadenitis in Children After the
      Discontinuation of Mandatory Bacillus Calmette and GuErin Immunization in France.
AB  - Eighty-five children were diagnosed with culture-confirmed nontuberculous
      mycobacterial cervical lymphadenitis within the MYCOMED surveillance network from
      2004 to 2013. The mean incidence sharply increased from 0.57 to 3.7 per 100,000
      children per year, after the discontinuation of mandatory bacillus Calmette and
      Guerin immunization in 2007. Cases were documented as Mycobacterium avium
      (62.3%), Mycobacterium intracellulare (15.3%) and Mycobacterium lentiflavum
      (12.9%). Outcome was favorable in all, with or without surgery or
      antimycobacterial treatment.

PMID- 29570592
TI  - Preterm Children Have Higher Risk Than Full-term Children of Invasive
      Pneumococcal Disease During the First 2 Years of Life.
AB  - BACKGROUND: A few previous studies have reported an increased risk of invasive
      pneumococcal disease (IPD) in children born preterm, but this has not been
      investigated in a cohort study. The impact of 7-valent pneumococcal conjugate
      vaccine (PCV7) on IPD incidence rates in preterm children is unknown. METHODS:
      Data from the Medical Birth Registry of Norway (2002-2010) were linked to other
      national registries. In total, 628,138 children were included in our study and
      followed until 2 years of age. Incidence rate ratios (IRRs) and confidence
      intervals (CIs) were estimated with Poisson regression. RESULTS: We identified
      411 cases of IPD. We observed higher rates of IPD in preterm than in full-term
      children for the intervals 0-23, 0-5 and 6-23 months of age, IRRs = 1.83 (95 %
      CI: 1.36-2.47), 2.95 (95% CI: 1.44-6.06) and 1.69 (95% CI: 1.22-2.34),
      respectively. The risk for IPD was reduced in the PCV7-period (2007-2010)
      compared with that of the pre PCV7-period (2002-2005) for children 6-23 months of
      age, IRRs = 0.20 (95% CI: 0.08-0.53) for preterm children and 0.28 (95% CI: 0.21
      0.38) for full-term children, but not for those 0-5 months of age, IRRs = 1.94
      (95% CI: 0.48-7.80) and 0.71 (95% CI: 0.38-1.33). CONCLUSIONS: Preterm children
      had an increased risk of IPD. After introduction of PCV7, the rate of IPD was
      reduced among preterm and full-term children from 6 months of age.

PMID- 29570593
TI  - Initial Palivizumab Dose Administration in Outpatient Clinic After Hospital
      Discharge.
AB  - BACKGROUND: Palivizumab provides passive immunity for respiratory syncytial virus
      (RSV), but poor adherence compromises protection. A hospital initiative promoted
      administration of first palivizumab doses at an outpatient clinic immediately
      after discharge. The objectives of this study were to evaluate the impact of the
      initiative on location and timing of first palivizumab dose, patient adherence,
      reimbursement, acquisition cost and RSV-positive hospital readmissions. METHODS:
      This retrospective cohort study included pediatric patients who received
      palivizumab from 2012 to 2016. Three groups were compared: "before initiative,"
      "transition" and "after initiative." Patients who did not qualify for palivizumab
      or who were eligible for palivizumab in previous RSV seasons were excluded.
      Multivariable logistic and linear regressions adjusted for patients'
      characteristics were used in outcome analysis. RESULTS: After adjusting for
      patients' characteristics, there was a 13.5-fold (95% confidence interval: 5.9
      30.5, P < 0.0001) increase in odds that patients would receive outpatient
      administration of palivizumab and 2.7-fold (95% confidence interval: 1.3-5.7, P =
      0.0103) increase in odds of receiving the second dose within 35 days after
      initiative implementation compared with before. Although there was no significant
      difference in reimbursement percentage after initiative implementation (32% +/-
      30% after initiative and 31% +/- 22% before), calculated palivizumab acquisition
      costs were 20.8% lower. RSV readmissions were not significantly different.
      CONCLUSIONS: Implementation of an initiative with defined workflow,
      multidisciplinary collaboration, and early case management efforts to obtain
      insurance authorization increased outpatient administration of first palivizumab
      doses. Patient adherence improved as demonstrated by more timely receipt of the
      second palivizumab dose. There was no difference in reimbursement; however,
      acquisition cost decreased which is valuable considering low reimbursement rates.
      RSV-positive readmissions did not change significantly.

PMID- 29570594
TI  - Acute Neuromuscular Adaptations in Response to Low-Intensity Blood-Flow
      Restricted Exercise and High-Intensity Resistance Exercise: Are There Any
      Differences?
AB  - Fatela, P, Reis, JF, Mendonca, GV, Freitas, T, Valamatos, MJ, Avela, J, and Mil
      Homens, P. Acute neuromuscular adaptations in response to low-intensity blood
      flow restricted exercise and high-intensity resistance exercise: are there any
      differences? J Strength Cond Res 32(4): 902-910, 2018-Numerous studies have
      reported similar neuromuscular adaptations between low-intensity (LI) blood-flow
      restricted exercise (BFRE) and high-intensity (HI) resistance training.
      Unfortunately, none of these experimental designs individualized blood flow
      restriction (BFR) levels to each participant. Thus, their findings are difficult
      to interpret. We aimed at comparing the acute effects of LI BFR (80% of absolute
      vascular occlusion pressure) with LI non-BFR and HI training on muscle torque,
      activation, and neuromuscular fatigue. Ten men (23.8 +/- 5.4 years) exercised at
      20 and 75% of 1 repetition maximum with and without BFR (for LI). Blood flow
      restriction pressure was determined individually using resting blood-flow
      measurements. Torque was determined during maximal voluntary contractions (MVCs)
      at pre-exercise and postexercise time points. Surface electromyographic activity
      (root mean square [RMS] and median frequency [MF]) was recorded for the rectus
      femoris (RF) and vastus medialis (VM) muscles, before and after each session of
      training, during isometric contractions at 20% MVC. Torque decreased post-HI and
      LI BFR (-9.5 and -7.8%, respectively; p < 0.01), but not after LI non-BFR. The MF
      was reduced following HI training in the VM and the RF muscles (-5.3 and -12.5%,
      respectively; p <= 0.05). Conversely, the impact of LI BFR on reducing MF was
      limited to the RF muscle (-10.7%, p <= 0.05). Finally, when compared to all other
      conditions, RMS values were consistently higher during submaximal contractions
      performed after HI training (p <= 0.05). Thus, we conclude that, despite
      enhancing the acute magnitude of muscular activation and fatigue, LI BFR exercise
      exerts a less profound impact on neuromuscular function than HI resistance
      training.

PMID- 29570595
TI  - Influence of a Cluster Set Configuration on the Adaptations to Short-Term Power
      Training.
AB  - Morales-Artacho, AJ, Padial, P, Garcia-Ramos, A, Perez-Castilla, A, and Feriche,
      B. Influence of a cluster set configuration on the adaptations to short-term
      power training. J Strength Cond Res 32(4): 930-937, 2018-This study investigated
      the effects of a traditional (TT) vs. cluster (CT) resistance training on the
      lower-body force, velocity, and power output. Nineteen males were allocated to a
      CT or a TT group and took part of a 3-week resistance training (2 weekly
      sessions). CT involved 6 sets of 3 * 2 repetitions (30 seconds rest every 2
      repetitions and 4 minutes 30 seconds between sets). TT comprised 6 sets of 6
      continuous repetitions (5 minutes rest between sets). Before and after the
      training period, force (F25, F50, F75), velocity (V25, V50, V75), and power (P25,
      P50, P75) were obtained during the countermovement jump (CMJ) exercise at 3
      external loading conditions (25, 50, and 75% of body mass). Individual linear
      regressions were used to determine the force-velocity profile including the
      Slope, estimated maximal theoretical force (F0), velocity (V0), and power (P0).
      After CT, very-likely moderate increments in P25 were observed compared with TT
      (p = 0.011, ES = 0.55) because of a very-likely moderate rise in V25 (p = 0.001,
      ES = 0.71). No significant differences were observed in any of the F-v profile
      variables between the TT and CT groups (p >= 0.207, ES <= 0.31). Our results
      suggest that 3 weeks of muscle power training including cluster set
      configurations are more efficient at inducing velocity and power adaptations
      specific to the training load.

PMID- 29570596
TI  - Quantifying the Physical Response to a Contemporary Amateur Boxing Simulation.
AB  - Finlay, MJ, Greig, M, and Page, RM. Quantifying the physical response to a
      contemporary amateur boxing simulation. J Strength Cond Res 32(4): 1005-1012,
      2018-This study examined the physical response to a contemporary boxing-specific
      exercise protocol (BSEP), based on notational analysis of amateur boxing. Nine
      male senior elite amateur boxers completed a 3 * 3-minute BSEP, with a 1-minute
      passive recovery period interspersing each round. Average (HRave) and peak
      (HRpeak) heart rates, average (V[Combining Dot Above]O2ave) and peak oxygen
      consumptions (V[Combining Dot Above]O2peak), blood lactate (BLa) concentrations,
      rating of perceived exertion, and both triaxial and uniaxial PlayerLoad metrics
      were recorded during the completion of the BSEP. Blood lactate concentration
      increased significantly in each round (Round 1 = 2.4 +/- 1.3 mmol.L; Round 2 =
      3.3 +/- 1.7 mmol.L; Round 3 = 4.3 +/- 2.6 mmol.L). Significantly lower HRave and
      HRpeak values were found in the first round (HRave: 150 +/- 15 b.min; HRpeak: 162
      +/- 12 b.min) when compared with the second (HRave: 156 +/- 16 b.min; HRpeak: 166
      +/- 13 b.min) and third (HRave: 150 +/- 15 b.min; HRpeak: 169 +/- 14 b.min). No
      significant differences were found in any of the V[Combining Dot Above]O2 or
      PlayerLoad metrics recorded during the BSEP. The BSEP based on notational
      analysis elicited a fatigue response across rounds, confirming its validity. The
      BSEP can be used as a training tool for boxing-specific conditioning with
      implications for reduced injury risk, and to assess the physical response to
      boxing-specific interventions. Moreover, the BSEP can also be manipulated to suit
      all levels of participants or training phases, with practical applications in
      performance monitoring and microcycle periodization.

PMID- 29570597
TI  - Maximum Dynamic Lower-Limb Strength Was Maintained During 24-Week Reduced
      Training Frequency in Previously Sedentary Older Women.
AB  - Walker, S, Serrano, J, and Van Roie, E. Maximum dynamic lower-limb strength was
      maintained during 24-week reduced training frequency in previously sedentary
      older women. J Strength Cond Res 32(4): 1063-1071, 2018-There is little study
      into the effects of reducing strength training below the recommended twice weekly
      frequency, particularly in older women, despite the possibility that individuals
      will encounter periods of reduced training frequency. The purpose of the present
      study was to determine the effects of a period of reduced training frequency on
      maximum strength and muscle mass of the lower limbs in comparison with the
      recommended training frequency of twice per week. After an initial 12-week
      period, where all subjects trained twice per week, a reduced strength training
      group (RST) trained once per week, whereas another strength training group (ST)
      continued to train twice per week for 24 weeks. A nontraining age-matched control
      group (CON) was used for comparison. All subjects were tested for leg press 1
      repetition maximum (1RM), electromyogram (EMG) amplitude of vastus lateralis and
      medialis, and quadriceps cross-sectional area (CSA) measured by panoramic
      ultrasound at weeks 0, 12, and 36. Both ST and RST continued to increase 1RM
      during the reduced training frequency period compared with control (~8% and ~5%
      vs. ~-3%, respectively; p <= 0.05). Accompanying these changes were significant
      increases in EMG amplitude in both ST and RST (p <= 0.05). However, the initial
      gains in quadriceps CSA made from week 0 to week 12 in RST were lost when
      training once per week (RST ~-5%). Therefore, reduced training frequency in this
      population does not adversely affect maximum strength or muscle activity but can
      negatively affect muscle mass, even reversing training-induced gains. Older
      individuals not training at least twice per week may compromise potential
      increases in muscle mass, important in counteracting effects of aging.

PMID- 29570598
TI  - Effects of Resistance Training on Cardiovascular Function in Patients With
      Peripheral Artery Disease: A Randomized Controlled Trial.
AB  - Gomes, APF, Correia, MA, Soares, AHG, Cucato, GG, Lima, AHRA, Cavalcante, BR,
      Sobral-Filho, DC, and Ritti-Dias, RM. Effects of resistance training on
      cardiovascular function in patients with peripheral artery disease: A randomized
      controlled trial. J Strength Cond Res 32(4): 1072-1080, 2018-The aim of this
      study was to analyze the effects of resistance training on cardiovascular
      function of patients with peripheral artery disease (PAD). In total, 30 patients
      with PAD were invited to participate in this randomized controlled trial,
      randomly allocated to a control (n = 15, 66 +/- 2 years; stretching and
      relaxation exercises) or resistance training group (n = 15, 60 +/- 3 years; 3
      sets of 10 repetitions of 8 whole-body exercises, with a 2-minute interval
      between sets). Resting and 24-hour blood pressure (BP), cardiac output, systemic
      vascular resistance, and autonomic variables were obtained before and after 12
      weeks of intervention. A blinded investigator performed all analyses. After 12
      weeks of intervention there was maintenance of resting systolic, diastolic, and
      mean BP (p > 0.18), cardiac output (p = 0.46), and systemic vascular resistance
      (p = 0.55) in both groups. There was a time effect reduction in heart rate (p =
      0.02), accompanied by changes in cardiac autonomic modulation (p = 0.03). There
      were no changes in 24-hour systolic, diastolic, and mean BP, heart rate, or rate
      pressure product (p > 0.05). The BP variability decreased in systolic (asleep, p
      = 0.003), diastolic (24 hours and awake, p = 0.001), and mean (24 hours and
      asleep, p < 0.02) only in the resistance training (RT) group. Twelve weeks of RT
      did not change resting and 24-hour BP, or their hemodynamic and autonomic
      determinants in patients with PAD; however, there were decreases in BP
      variability, indicating that it could be considered as an alternative to reducing
      cardiovascular risk in patients with PAD.

PMID- 29570599
TI  - Increased Leg Bone Mineral Density and Content During the Initial Years of
      College Sport.
AB  - Scerpella, JJ, Buehring, B, Hetzel, SJ, and Heiderscheit, BC. Increased leg bone
      mineral density and content during the initial years of college sport. J Strength
      Cond Res 32(4): 1123-1130, 2018-Bone mineral density (BMD) and bone mineral
      content (BMC) data are useful parameters for evaluating how training practices
      promote bone health. We used dual-energy X-ray absorptiometry (DXA) to
      longitudinally assess sport-specific growth in leg and total body BMD/BMC over
      the initial 2 years of collegiate training. Eighty-five Division 1 collegiate
      basketball, hockey, and soccer athletes (50 males and 35 females; age 19.0 [0.8]
      years) underwent annual DXA scans. Leg and total body BMD/BMC were compared
      within and across two 1-year intervals (periods 1 and 2) using repeated-measures
      analysis of variance, adjusting for age, sex, race, and sport. Leg BMD, leg BMC,
      and total body BMC all increased over period 1 (0.05 g.cm [p = 0.001], 0.07 kg [p
      = 0.002], and 0.19 kg [p < 0.001] respectively). Changes in period 2 compared
      with period 1 were smaller for leg BMD (p = 0.001), leg BMC (p < 0.001), leg fat
      mass (p = 0.028), and total BMC (p = 0.005). Leg lean mass increased more during
      period 2 than period 1 (p = 0.018). Sports participation was the only significant
      predictor of change in leg BMD. Significant increases in both leg BMD and BMC
      were demonstrated over both 2-year periods, with greater gains during period 1.
      These gains highlight the importance of attentive training procedures,
      capitalizing on attendant physical benefits of increased BMD/BMC. Additional
      research in young adults, evaluating bone mass acquisition, will optimize
      performance and decrease risk of bone stress injury among collegiate athletes.

PMID- 29570600
TI  - The Age of Peak Marathon Performance in Cross-Country Skiing-The "Engadin Ski
      Marathon".
AB  - Knechtle, B and Nikolaidis, PT. The age of peak marathon performance in cross
      country skiing-the "Engadin Ski Marathon." J Strength Cond Res 32(4): 1131-1136,
      2018-The age of the best endurance performance has been well investigated in flat
      city running marathons. However, we have no knowledge about the age of peak
      marathon performance in cross-country skiing, which would be of great practical
      value for athletes and coaches. Therefore, the aim of the present study was to
      examine the age of peak marathon performance in cross-country skiing.
      Participants were 162,991 men and 34,833 women competing between 1998 and 2016 in
      the "Engadin Ski Marathon." We considered the fastest for both women and men, and
      all finishers in 1-year age intervals. The men-to-women ratio increased across
      ages (r = 0.55, p < 0.0001). Men (44.27 +/- 0.03 years, 15.73 +/- 0.01 km.h) were
      5.98 +/- 0.07 years older and 2.14 +/- 0.02 km.h faster (p < 0.0001) than women
      (38.29 +/- 0.06 years, 13.58 +/- 0.01 km.h). Considering the fastest participants
      in 1-year age intervals, the fastest speed for men (30.33 km.h) was achieved at
      the age of 29 years, and for women (28.76 km.h) at the age of 24 years.
      Considering all participants, the fastest speed for men (17.69 km.h) was observed
      at the age of 18 years, whereas for women (15.76 km.h) it was at the age of 17
      years. In summary, for athletes and coaches, the age of peak performance in cross
      country skiers competing in a marathon distance was much younger and closer to
      the peak of aerobic capacity than what was found by previous studies in marathon
      road runners.

PMID- 29570601
TI  - Effect of Compression Garments on Controlled Force Output After Heel-Rise
      Exercise.
AB  - Kato, E, Nakamura, M, and Takahashi, H. Effect of compression garments on
      controlled force output after heel-rise exercise. J Strength Cond Res 32(4): 1174
      1179, 2018-The purpose of this study was to elucidate the effects of compression
      garments (CG) on controlled force output after strenuous exercise. Sixteen
      healthy volunteers completed trials both with CG and without CG (control trial:
      CON) on 2 separate, random days which were at least 1 month apart. Both trials
      required participants to perform heel-rise exercises from maximal dorsiflexion to
      maximal plantar flexion 20 times with a single leg. The subjects repeated 3 sets
      of the exercise and took a rest for 2 minutes between sets. Before and after the
      heel-rise exercise, mechanical (stiffness) and architectural properties of the
      gastrocnemius medialis muscle were evaluated using the ultrasound method. Also,
      isometric maximal voluntary contraction (MVC) of plantar flexion was measured,
      and the subjects maintained 20% MVC of plantar flexion torque for 20 seconds as
      steadily as possible (steadiness task) as an index of force control. Repeated 2
      way analysis of variance analysis (CG/CON * time) indicated that all the
      parameters declined immediately after heel-rise exercise in both CG and CON
      trials. Maximal voluntary contraction did not show different tendencies between
      CG and CON trials, but muscle stiffness and steadiness declined less in CG than
      CON (p < 0.05). In conclusion, CG are considered to positively benefit controlled
      force output after strenuous exercise.

PMID- 29570602
TI  - Live Bacterial Vectors-A Promising DNA Vaccine Delivery System.
AB  - Vaccination is one of the most successful immunology applications that has
      considerably improved human health. The DNA vaccine is a new vaccine being
      developed since the early 1990s. Although the DNA vaccine is promising, no human
      DNA vaccine has been approved to date. The main problem facing DNA vaccine
      efficacy is the lack of a DNA vaccine delivery system. Several studies explored
      this limitation. One of the best DNA vaccine delivery systems uses a live
      bacterial vector as the carrier. The live bacterial vector induces a robust
      immune response due to its natural characteristics that are recognized by the
      immune system. Moreover, the route of administration used by the live bacterial
      vector is through the mucosal route that beneficially induces both mucosal and
      systemic immune responses. The mucosal route is not invasive, making the vaccine
      easy to administer, increasing the patient's acceptance. Lactic acid bacterium is
      one of the most promising bacteria used as a live bacterial vector. However, some
      other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp.,
      have been used as DNA vaccine carriers. Numerous studies showed that live
      bacterial vectors are a promising candidate to deliver DNA vaccines.

PMID- 29570603
TI  - Real-Time Estimation of Population Exposure to PM2.5 Using Mobile- and Station
      Based Big Data.
AB  - Extremely high fine particulate matter (PM2.5) concentration has been a topic of
      special concern in recent years because of its important and sensitive relation
      with health risks. However, many previous PM2.5 exposure assessments have
      practical limitations, due to the assumption that population distribution or air
      pollution levels are spatially stationary and temporally constant and people move
      within regions of generally the same air quality throughout a day or other time
      periods. To deal with this challenge, we propose a novel method to achieve the
      real-time estimation of population exposure to PM2.5 in China by integrating
      mobile-phone locating-request (MPL) big data and station-based PM2.5
      observations. Nationwide experiments show that the proposed method can yield the
      estimation of population exposure to PM2.5 concentrations and cumulative inhaled
      PM2.5 masses with a 3-h updating frequency. Compared with the census-based
      method, it introduced the dynamics of population distribution into the exposure
      estimation, thereby providing an improved way to better assess the population
      exposure to PM2.5 at different temporal scales. Additionally, the proposed method
      and dataset can be easily extended to estimate other ambient pollutant exposures
      such as PM10, O3, SO2, and NO2, and may hold potential utilities in supporting
      the environmental exposure assessment and related policy-driven environmental
      actions.

PMID- 29570604
TI  - Remarkably Enhanced Room-Temperature Hydrogen Sensing of SnO2 Nanoflowers via
      Vacuum Annealing Treatment.
AB  - In this work, SnO2 nanoflowers synthesized by a hydrothermal method were employed
      as hydrogen sensing materials. The as-synthesized SnO2 nanoflowers consisted of
      cuboid-like SnO2 nanorods with tetragonal structures. A great increase in the
      relative content of surface-adsorbed oxygen was observed after the vacuum
      annealing treatment, and this increase could have been due to the increase in
      surface oxygen vacancies serving as preferential adsorption sites for oxygen
      species. Annealing treatment resulted in an 8% increase in the specific surface
      area of the samples. Moreover, the conductivity of the sensors decreased after
      the annealing treatment, which should be attributed to the increase in electron
      scattering around the defects and the compensated donor behavior of the oxygen
      vacancies due to the surface oxygen adsorption. The hydrogen sensors of the
      annealed samples, compared to those of the unannealed samples, exhibited a much
      higher sensitivity and faster response rate. The sensor response factor and
      response rate increased from 27.1% to 80.2% and 0.34%/s to 1.15%/s, respectively.
      This remarkable enhancement in sensing performance induced by the annealing
      treatment could be attributed to the larger specific surface areas and higher
      amount of surface-adsorbed oxygen, which provides a greater reaction space for
      hydrogen. Moreover, the sensors with annealed SnO2 nanoflowers also exhibited
      high selectivity towards hydrogen against CH4, CO, and ethanol.

PMID- 29570605
TI  - Molecular Characterization of a Novel Species of Capillovirus from Japanese
      Apricot (Prunus mume).
AB  - With the increased use of high-throughput sequencing methods, new viruses
      infecting Prunus spp. are being discovered and characterized, especially in the
      family Betaflexiviridae. Double-stranded RNAs from symptomatic leaves of a
      Japanese apricot (Prunusmume) tree from Japan were purified and analyzed by
      Illumina sequencing. Blast comparisons of reconstructed contigs showed that the
      P. mume sample was infected by a putative novel virus with homologies to Cherry
      virus A (CVA) and to the newly described Currant virus A (CuVA), both members of
      genus Capillovirus. Completion of the genome showed the new agent to have a
      genomic organization typical of capilloviruses, with two overlapping open reading
      frames encoding a large replication-associated protein fused to the coat protein
      (CP), and a putative movement protein (MP). This virus shares only, respectively,
      63.2% and 62.7% CP amino acid identity with the most closely related viruses, CVA
      and CuVA. Considering the species demarcation criteria in the family and
      phylogenetic analyses, this virus should be considered as representing a new
      viral species in the genus Capillovirus, for which the name of Mume virus A is
      proposed.

PMID- 29570606
TI  - Facilitating Anti-Cancer Combinatorial Drug Discovery by Targeting Epistatic
      Disease Genes.
AB  - Due to synergistic effects, combinatorial drugs are widely used for treating
      complex diseases. However, combining drugs and making them synergetic remains a
      challenge. Genetic disease genes are considered a promising source of drug
      targets with important implications for navigating the drug space. Most diseases
      are not caused by a single pathogenic factor, but by multiple disease genes, in
      particular, interacting disease genes. Thus, it is reasonable to consider that
      targeting epistatic disease genes may enhance the therapeutic effects of
      combinatorial drugs. In this study, synthetic lethality gene pairs of tumors,
      similar to epistatic disease genes, were first targeted by combinatorial drugs,
      resulting in the enrichment of the combinatorial drugs with cancer treatment,
      which verified our hypothesis. Then, conventional epistasis detection software
      was used to identify epistatic disease genes from the genome wide association
      studies (GWAS) dataset. Furthermore, combinatorial drugs were predicted by
      targeting these epistatic disease genes, and five combinations were proven to
      have synergistic anti-cancer effects on MCF-7 cells through cell cytotoxicity
      assay. Combined with the three-dimensional (3D) genome-based method, the
      epistatic disease genes were filtered and were more closely related to disease.
      By targeting the filtered gene pairs, the efficiency of combinatorial drug
      discovery has been further improved.

PMID- 29570607
TI  - Effect of Commercially Available Sugar-Sweetened Beverages on Subjective Appetite
      and Short-Term Food Intake in Girls.
AB  - BACKGROUND: The effect of sugar-sweetened beverages (SSBs) on satiety and short
      term food intake (FI) regulation in girls has received little attention. The
      objective of the present study was to compare the effect of pre-meal consumption
      of commercially available SSBs on subjective appetite and short-term FI in 9-14
      year-old girls. The methods we used include using a randomized crossover design
      in which 28 girls consumed isovolumetric amounts (350 mL) of a fruit drink (154
      kcal), cola (158 kcal), 1% chocolate milk (224 kcal), or water (control; 0 kcal)
      on four separate mornings. Subjective appetite and thirst were measured at
      regular intervals via visual analogue scales (VAS) and FI was assessed at 60 min
      post-beverage consumption. The results show that subjective appetite and thirst
      decreased after all beverages, but did not differ among beverages. Short-term FI
      was suppressed following consumption of chocolate milk (15%; p < 0.001) and cola
      (11%; p = 0.02) compared to the water control. However, cumulative energy intake
      (beverage (kcal) + test meal (kcal)) was not affected by beverage type. In
      conclusion, chocolate milk and cola, but not fruit drink, suppressed FI in girls
      while cumulative FI did not differ among treatments.

PMID- 29570609
TI  - Synthesis of Magnesium Nickel Boride Aggregates via Borohydride Autogenous
      Pressure.
AB  - We demonstrate synthesis of the ternary intermetallic MgNi3B2 using autogenous
      pressure from the reaction of NaBH4 with Mg and Ni metal powder. The
      decomposition of NaBH4 to H2 and B2H6 commences at low temperatures in the
      presence of Mg and/or Ni and promotes formation of Ni-borides and MgNi3B2 with
      the increase in temperature. MgNi3B2 aggregates with Ni-boride cores are formed
      when the reaction temperature is >670  degrees C and autogenous pressure is >1.7
      MPa. Morphologies and microstructures suggest that solid-gas and liquid-gas
      reactions are dominant mechanisms and that Ni-borides form at a lower temperature
      than MgNi3B2. Magnetic measurements of the core-shell MgNi3B2 aggregates are
      consistent with ferromagnetic behaviour in contrast to stoichiometric MgNi3B2
      which is diamagnetic at room temperature.

PMID- 29570608
TI  - Antioxidative Effect of Quetiapine on Acute Ultraviolet-B-Induced Skin and HaCaT
      Cell Damage.
AB  - Quetiapine is a new type of antipsychotic drug, with effective protection of
      pheochromocytoma PC12 cells from oxidative stress-induced apoptosis. Ultraviolet
      B radiation can increase reactive oxygen species (ROS) production, resulting in
      significant inflammatory responses in damaged skin. Thus, the purpose of this
      study is to explore whether quetiapine protects the skin from intermediate-wave
      ultraviolet (UVB)-induced damage through antioxidant stress. In vivo, we found
      quetiapine treatment was able to significantly decrease skin thickness, erythema,
      and edema, as well as inflammation compared to control group. Moreover,
      quetiapine treatment increased the activities of antioxidant enzymes, including
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, it
      reduced the production of malondialdehyde (MDA), a kind of oxidized lipid. In
      vitro, we found that quetiapine blocked UVB-induced intracellular ROS generation
      and maintained the cell activity at a normal level. Furthermore, we tested the
      phosphorylation of p38 both in vivo and in vitro, and we found that quetiapine
      could inhibit phosphorylation of p38, which is caused by UVB irradiation. We
      concluded that quetiapine was able to relieve UVB-induced skin damage through its
      antioxidative properties. These effects might be associated with p38 MAPK
      signaling pathway.

PMID- 29570610
TI  - Dietary Sialyllactose Does Not Influence Measures of Recognition Memory or
      Diurnal Activity in the Young Pig.
AB  - Sialic acid (SA) is an integral component of gangliosides and signaling molecules
      in the brain and its dietary intake may support cognitive development. We
      previously reported that feeding sialyllactose, a milk oligosaccharide that
      contains SA, alters SA content and diffusivity in the pig brain. The present
      research sought to expand upon such results and describe the effects of feeding
      sialyllactose on recognition memory and sleep/wake activity using a translational
      pig model. Pigs were provided ad libitum access to a customized milk replacer
      containing 0 g/L or 380 g/L of sialyllactose from postnatal day (PND) 2-22.
      Beginning on PND 15, pigs were fitted with accelerometers to track home-cage
      activity and testing on the novel object recognition task began at PND 17. There
      were no significant effects of diet on average daily body weight gain, average
      daily milk intake, or the gain-to-feed ratio during the study (all p >= 0.11).
      Pigs on both diets were able to display recognition memory on the novel object
      recognition task (p < 0.01), but performance and exploratory behavior did not
      differ between groups (all p >= 0.11). Total activity and percent time spent
      sleeping were equivalent between groups during both day and night cycles (all p
      >= 0.56). Dietary sialyllactose did not alter growth performance of young pigs,
      and there was no evidence that providing SA via sialyllactose benefits the
      development of recognition memory or gross sleep-related behaviors.

PMID- 29570611
TI  - Macular Xanthophylls Are Related to Intellectual Ability among Adults with
      Overweight and Obesity.
AB  - Excess adiposity or obesity has been inversely related to cognitive function and
      macular xanthophyll status. However, whether the neuroprotective effects of
      macular xanthophylls on cognitive function are independent of excess adiposity is
      unclear. We investigated the relationship between macular xanthophylls and
      intellectual ability among adults (N = 114) between 25 and 45 years with
      overweight and obesity (>=25 kg/m2). Dual energy X-ray absorptiometry and
      heterochromatic flicker photometry were used to assess whole body adiposity
      (%Fat) and macular pigment optical density (MPOD), respectively. Dietary
      xanthophylls (lutein and zeaxanthin) were assessed using 7-day diet records. The
      Kaufman Brief Intelligence Test-2 (KBIT-2) was used to assess general
      intelligence (IQ) as well as fluid and crystallized intelligence. Bivariate
      correlations revealed that MPOD was inversely related to %Fat and positively
      associated with IQ and fluid intelligence. Although %Fat was inversely correlated
      to IQ and fluid intelligence, this relationship did not persist following
      adjustment for sex and MPOD. Further, MPOD was an independent predictor of IQ and
      fluid intelligence. However, no significant relationships were observed between
      MPOD and crystalized intelligence. These results suggest that macular
      xanthophylls are selectively related to fluid intelligence, regardless of degree
      of adiposity among adults with overweight and obesity.

PMID- 29570612
TI  - Synthesis, Optical, and Structural Studies of Iron Sulphide Nanoparticles and
      Iron Sulphide Hydroxyethyl Cellulose Nanocomposites from Bis
      (Dithiocarbamato)Iron(II) Single-Source Precursors.
AB  - In this study, Fe(II) complexes of phenyldithiocarbamate, dimethyldithiocarbamate
      and imidazolyldithiocarbamate were used as single-source precursors to prepare
      iron sulphide nanoparticles by thermolysis in oleic acid/octadecylamine (ODA) at
      180  degrees C. The nanoparticles were dispersed into hydroxyethyl cellulose
      (HEC) to prepare iron sulphide/HEC nanocomposites. Ultraviolet-Visible (UV-Vis),
      Photoluminescence (PL), Fourier Transform Infrared (FTIR), powder X-ray
      diffraction (pXRD), high-resolution transmission electron microscopy (HRTEM),
      Field emission scanning electron microscopy (FESEM), and energy dispersive X-ray
      spectroscopy (EDS) were used to characterize the iron sulphide nanoparticles and
      corresponding HEC nanocomposites. The absorption spectra studies revealed that
      the nanoparticles were blue shifted due to quantum confinement and the optical
      band gaps of the nanoparticles are 4.85 eV for FeS1, 4.36 eV for FeS2, and 4.77
      eV for FeS3. The emission maxima are red-shifted and broader for the
      nanoparticles prepared from phenyldithiocarbamate. Rod-like and spherically
      shaped iron sulphide particles were observed from the HRTEM images. The
      crystallite sizes from the HRTEM images are 23.90-38.89 nm for FeS1, 4.50-10.50
      nm for FeS2, and 6.05-6.19 nm for FeS3 iron sulphide nanoparticles, respectively.
      pXRD diffraction patterns confirmed that FeS1 is in the pyrrhotite-4M crystalline
      phase, FeS2 is in the pyrrhotite phase, and FeS3 is in the troilite phase of iron
      sulphide. The phases of the iron sulphide nanoparticles indicate that the nature
      of the precursor complex affects the obtained crystalline phase. FTIR spectra
      studies confirmed the incorporation of the nanoparticles in the HEC matrix by the
      slight shift of the O-H and C-O bonds and the intense peaks on the nanoparticles.
      FESEM images of the iron sulphide nanoparticles showed flake-like or leaf-like
      morphologies with some hollow spheres. The EDS confirmed the formation of iron
      sulphide nanoparticles by showing the peaks of Fe and S.

PMID- 29570613
TI  - Branched Chain Amino Acids: Beyond Nutrition Metabolism.
AB  - Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile),
      and valine (Val), play critical roles in the regulation of energy homeostasis,
      nutrition metabolism, gut health, immunity and disease in humans and animals. As
      the most abundant of essential amino acids (EAAs), BCAAs are not only the
      substrates for synthesis of nitrogenous compounds, they also serve as signaling
      molecules regulating metabolism of glucose, lipid, and protein synthesis,
      intestinal health, and immunity via special signaling network, especially
      phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin
      (PI3K/AKT/mTOR) signal pathway. Current evidence supports BCAAs and their
      derivatives as the potential biomarkers of diseases such as insulin resistance
      (IR), type 2 diabetes mellitus (T2DM), cancer, and cardiovascular diseases
      (CVDs). These diseases are closely associated with catabolism and balance of
      BCAAs. Hence, optimizing dietary BCAA levels should have a positive effect on the
      parameters associated with health and diseases. This review focuses on recent
      findings of BCAAs in metabolic pathways and regulation, and underlying the
      relationship of BCAAs to related disease processes.

PMID- 29570614
TI  - Transcriptomic and GC-MS Metabolomic Analyses Reveal the Sink Strength Changes
      during Petunia Anther Development.
AB  - Petunia, which has been prevalently cultivated in landscaping, is a
      dicotyledonous herbaceous flower of high ornamental value. Annually, there is a
      massive worldwide market demand for petunia seeds. The normal development of
      anther is the necessary prerequisite for the plants to generate seeds. However,
      the knowledge of petunia anther development processes is still limited. To better
      understand the mechanisms of petunia anther development, the transcriptomes and
      metabolomes of petunia anthers at three typical development stages were
      constructed and then used to detect the gene expression patterns and primary
      metabolite profiles during the anther development processes. Results suggested
      that there were many differentially-expressed genes (DEGs) that mainly
      participated in photosynthesis and starch and sucrose metabolism when DEGs were
      compared between the different development stages of anthers. In this study,
      fructose and glucose, which were involved in starch and sucrose metabolism, were
      taken as the most important metabolites by partial least-squares discriminate
      analysis (PLS-DA). Additionally, the qRT-PCR analysis of the photosynthetic
      related genes all showed decreased expression trends along with the anther
      development. These pieces of evidence indicated that the activities of energy and
      carbohydrate metabolic pathways were gradually reduced during all the development
      stages of anther, which affects the sink strength. Overall, this work provides a
      novel and comprehensive understanding of the metabolic processes in petunia
      anthers.

PMID- 29570615
TI  - Neuroimmune Tau Mechanisms: Their Role in the Progression of Neuronal
      Degeneration.
AB  - Progressive neurodegenerative pathologies in aged populations are an issue of
      major concern worldwide. The microtubule-associated protein tau is able to self
      aggregate to form abnormal supramolecular structures that include small oligomers
      up to complex polymers. Tauopathies correspond to a group of diseases that share
      tau pathology as a common etiological agent. Since microglial cells play a
      preponderant role in innate immunity and are the main source of proinflammatory
      factors in the central nervous system (CNS), the alterations in the cross-talks
      between microglia and neuronal cells are the main focus of studies concerning the
      origins of tauopathies. According to evidence from a series of studies, these
      changes generate a feedback mechanism reactivating microglia and provoking
      constant cellular damage. Thus, the previously summarized mechanisms could
      explain the onset and progression of different tauopathies and their
      functional/behavioral effects, opening the window towards an understanding of the
      molecular basis of anomalous tau interactions. Despite clinical and pathological
      differences, increasing experimental evidence indicates an overlap between
      tauopathies and synucleinopathies, considering that neuroinflammatory events are
      involved and the existence of protein misfolding. Neurofibrillary tangles of
      pathological tau (NFT) and Lewy bodies appear to coexist in certain brain areas.
      Thus, the co-occurrence of synucleinopathies with tauopathies is evidenced by
      several investigations, in which NFT were found in the substantia nigra of
      patients with Parkinson's disease, suggesting that the pathologies share some
      common features at the level of neuroinflammatory events.

PMID- 29570616
TI  - Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis
      Patients: A Systematic Review and Limited Meta-Analysis.
AB  - Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis
      (HD) treatment and is linked to the development of premature atherosclerosis and
      mortality. The non-pharmacological approach to treat inflammation in HD patients
      through nutritional intervention is well cited. We aimed to assess the efficacy
      of different nutritional interventions at improving inflammatory outcomes in HD
      patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL
      6), and tumour necrosis factor-alpha (TNF-alpha). We searched PubMed, Cochrane
      Library, and Embase for randomized controlled trials (RCT) published before June
      2017. Inclusion criteria included RCTs on adult patients on maintenance HD
      treatment with duration of nutritional interventions for a minimum 4 weeks. Risk
      of bias was assessed using the Jadad score. In total, 46 RCTs experimenting
      different nutritional interventions were included in the review and categorized
      into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D,
      fibres, and probiotics. Meta-analyses indicated significant reduction in CRP
      levels by omega-3 fatty acids (Random model effect: -0.667 mg/L, p < 0.001) and
      vitamin E (fixed model effect: -0.257 mg/L, p = 0.005). Evidence for other groups
      of nutritional interventions was inconclusive. In conclusion, our meta-analysis
      provided evidence that omega-3 fatty acids and vitamin E could improve
      inflammatory outcomes in HD patients.

PMID- 29570617
TI  - Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral
      Neuropathy in Colorectal Cancer Patients.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side
      effect in colorectal cancer (CRC) patients. This study assessed the association
      between habitual dietary intake of magnesium or calcium and prevalence and
      severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For
      this prospective cohort study, 196 CRC patients were considered. Magnesium and
      calcium intake was determined using a food frequency questionnaire at diagnosis,
      during and after chemotherapy. Chronic CIPN was assessed 12 months after
      diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were
      calculated to assess the association between magnesium or calcium intake and the
      prevalence of CIPN. Multivariable linear regression analysis was used to assess
      the association between magnesium or calcium intake and severity of CIPN. CIPN
      was reported by 160 (82%) patients. Magnesium intake during chemotherapy was
      statistically significantly associated with lower prevalence of CIPN (prevalence
      ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher
      dietary intake of magnesium during (beta -1.08, 95% CI -1.95, -0.22) and after
      chemotherapy (beta -0.93, 95% CI -1.81, -0.06) was associated with less severe
      CIPN. No associations were found for calcium intake and the prevalence and
      severity of CIPN. To conclude, we observed an association between higher dietary
      magnesium intake and lower prevalence and severity of CIPN in CRC patients.

PMID- 29570619
TI  - Rhizosphere Microbiome Modulators: Contributions of Nitrogen Fixing Bacteria
      towards Sustainable Agriculture.
AB  - Rhizosphere microbiome which has been shown to enhance plant growth and yield are
      modulated or influenced by a few environmental factors such as soil type, plant
      cultivar, climate change and anthropogenic activities. In particular,
      anthropogenic activity, such as the use of nitrogen-based chemical fertilizers,
      is associated with environmental destruction and this calls for a more
      ecofriendly strategy to increase nitrogen levels in agricultural land. This feat
      is attainable by harnessing nitrogen-fixing endophytic and free-living
      rhizobacteria. Rhizobium, Pseudomonas, Azospirillum and Bacillus, have been found
      to have positive impacts on crops by enhancing both above and belowground biomass
      and could therefore play positive roles in achieving sustainable agriculture
      outcomes. Thus, it is necessary to study this rhizosphere microbiome with more
      sophisticated culture-independent techniques such as next generation sequencing
      (NGS) with the prospect of discovering novel bacteria with plant growth promoting
      traits. This review is therefore aimed at discussing factors that can modulate
      rhizosphere microbiome with focus on the contributions of nitrogen fixing
      bacteria towards sustainable agricultural development and the techniques that can
      be used for their study.

PMID- 29570618
TI  - Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance.
AB  - Although simple in structure, lysophosphatidic acid (LPA) is a potent bioactive
      lipid that profoundly influences cellular signaling and function upon binding to
      G protein-coupled receptors (LPA1-6). The majority of circulating LPA is produced
      by the secreted enzyme autotaxin (ATX). Alterations in LPA signaling, in
      conjunction with changes in autotaxin (ATX) expression and activity, have been
      implicated in metabolic and inflammatory disorders including obesity, insulin
      resistance, and cardiovascular disease. This review summarizes our current
      understanding of the sources and metabolism of LPA with focus on the influence of
      diet on circulating LPA. Furthermore, we explore how the ATX-LPA pathway impacts
      obesity and obesity-associated disorders, including impaired glucose homeostasis,
      insulin resistance, and cardiovascular disease.

PMID- 29570620
TI  - Dietary Fiber and Telomere Length in 5674 U.S. Adults: An NHANES Study of
      Biological Aging.
AB  - The relationship between fiber intake and telomere length was evaluated using a
      cross-sectional design and an NHANES sample of 5674 U.S. adults. Another purpose
      was to test the impact of potential confounders on the association. Fiber
      consumption was measured using a 24 h recall and telomere length was indexed
      using the quantitative polymerase chain reaction method. Overall, the U.S. adults
      had low fiber intake (median: 6.6 g per 1000 kcal)-less than one-half the
      recommendation of the Dietary Guidelines for Americans. With age, gender, race,
      housing status, and misreported energy intake controlled, the relationship
      between fiber intake per 1000 kcal and telomere length was linear (F = 9.5, p =
      0.0045). Specifically, for each 1 g increment in fiber intake per 1000 kcal,
      telomeres were 8.3 base pairs longer. Because each additional year of
      chronological age was associated with telomeres that were 15.5 base pairs
      shorter, results suggest that a 10 g increase in fiber intake per 1000 kcal would
      correspond with telomeres that are 83 base pairs longer. On average, this would
      equate to 5.4 fewer years of biologic aging (83 / 15.5). With smoking, BMI,
      alcohol use, and physical activity controlled, as well as the other covariates,
      each 10 g increment in fiber accounted for telomeres that were 67 base pairs
      longer (F = 7.6, p = 0.0101), a biologic aging difference of about 4.3 years. In
      conclusion, significant fiber consumption accounts for longer telomeres and less
      biologic aging than lower levels of fiber intake.

PMID- 29570622
TI  - Preparation of Hierarchical Highly Ordered Porous Films of Brominated
      Poly(phenylene oxide) and Hydrophilic SiO2/C Membrane via the Breath Figure
      Method.
AB  - Porous permeable films materials have very broad prospects in the treatment of
      sludge-containing waste water due to their large surface area and good
      microfiltration. In this work, highly ordered porous membranes have been prepared
      successfully on ice substrates using a poly(phenylene oxide) (BPPO)-SiO2
      nanoparticle (NP) mixture by the brePorous permeable films materials have very
      broad prospects in the treatment of sludge-containing waste water due to their
      large surface area and good microfiltration. In this work, highly ordered porous
      membranes have been prepared successfully on ice substrates using aath figure
      method. Based on the theory of Pickering emulsion system and capillary flow,
      particle assisted membrane formation was analyzed. Another two sorts of new
      membranes SiO2/C membrane and hierarchical porous polymer (HPP) membrane, which
      were obtained by modification of the BPPO-SiO2 membrane by calcination and
      etching, were set up in a further study. Their properties were investigated
      through the methods of scanning electron microscopy (SEM), fourier transform
      infrared spectrometry (FTIR), ultraviolet spectrum (UV), capillary
      electrophoresis (CE), contact angle, and water flux tests. All these results
      demonstrate that both surface hydrophilicity and fouling resistance of the
      membrane would be improved by using SiO2 as a filler. The membranes with high
      permeability and antifouling properties were used for microfiltration
      applications.

PMID- 29570621
TI  - The Melatonin Signaling Pathway in a Long-Term Memory In Vitro Study.
AB  - The activation of cyclic adenosine monophosphate (cAMP) response element-binding
      protein (CREB) via phosphorylation in the hippocampus is an important signaling
      mechanism for enhancing memory processing. Although melatonin is known to
      increase CREB expression in various animal models, the signaling mechanism
      between melatonin and CREB has been unknown in vitro. Thus, we confirmed the
      signaling pathway between the melatonin receptor 1 (MT1) and CREB using melatonin
      in HT-22 cells. Melatonin increased MT1 and gradually induced signals associated
      with long-term memory processing through phosphorylation of Raf, ERK, p90RSK,
      CREB, and BDNF expression. We also confirmed that the calcium, JNK, and AKT
      pathways were not involved in this signaling pathway by melatonin in HT-22 cells.
      Furthermore, we investigated whether melatonin regulated the expressions of CREB
      BDNF associated with long-term memory processing in aged HT-22 cells. In
      conclusion, melatonin mediated the MT1-ERK-p90RSK-CREB-BDNF signaling pathway in
      the in vitro long-term memory processing model and increased the levels of p-CREB
      and BDNF expression in melatonin-treated cells compared to untreated HT-22 cells
      in the cellular aged state. Therefore, this paper suggests that melatonin induces
      CREB signaling pathways associated with long-term memory processing in vitro.

PMID- 29570623
TI  - Correction: Becker, B. et al. Yeast Killer Toxin K28: Biology and Unique Strategy
      of Host Cell Intoxication and Killing.

PMID- 29570624
TI  - Recent Developments in Vinylsulfonium and Vinylsulfoxonium Salt Chemistry.
AB  - This review describes advances in the literature since 2000 in the area of
      reactions of vinylsulfonium and vinylsulfoxonium salts, with a particular
      emphasis on stereoselective examples. Although the chemistry of vinylsulfonium
      salts was first explored back in the 1950s, and that of vinylsulfoxonium salts in
      the early 1970s, there has been renewed interest in these compounds since the
      turn of the century. This has been largely due to an increased appreciation for
      the many synthetic possibilities associated with these valuable electrophiles.
      The development of improved routes to vinylsulfonium salts allowing for their in
      situ generation has played a part in accelerating their study. In general,
      reactions of the two sulfur salt classes follow a similar mechanistic pathway:
      initial conjugate addition of a nucleophile to the beta-position, followed by
      protonation of an ylide intermediate, and cyclization of tethered anion to afford
      monocyclic or bicyclic product (e.g., cyclopropane, aziridine, oxazole,
      oxazolidinone, gamma-lactam or gamma-lactone). Alternatively, reactions involve
      formation of an ylide intermediate followed by intramolecular Johnson-Corey
      Chaykovsky reaction (epoxidation or cyclopropanation), and subsequent cyclization
      to afford the desired bicyclic product (e.g., fused bicyclic epoxide or
      cyclopropane).

PMID- 29570625
TI  - Impact of Scyphozoan Venoms on Human Health and Current First Aid Options for
      Stings.
AB  - Cnidaria include the most venomous animals of the world. Among Cnidaria,
      Scyphozoa (true jellyfish) are ubiquitous, abundant, and often come into
      accidental contact with humans and, therefore, represent a threat for public
      health and safety. The venom of Scyphozoa is a complex mixture of bioactive
      substances-including thermolabile enzymes such as phospholipases,
      metalloproteinases, and, possibly, pore-forming proteins-and is only partially
      characterized. Scyphozoan stings may lead to local and systemic reactions via
      toxic and immunological mechanisms; some of these reactions may represent a
      medical emergency. However, the adoption of safe and efficacious first aid
      measures for jellyfish stings is hampered by the diffusion of folk remedies,
      anecdotal reports, and lack of consensus in the scientific literature. Species
      specific differences may hinder the identification of treatments that work for
      all stings. However, rinsing the sting site with vinegar (5% acetic acid) and the
      application of heat (hot pack/immersion in hot water) or lidocaine appear to be
      substantiated by evidence. Controlled clinical trials or reliable models of
      envenomation are warranted to confirm the efficacy and safety of these approaches
      and identify possible species-specific exceptions. Knowledge of the precise
      composition of Scyphozoa venom may open the way to molecule-oriented therapies in
      the future.

PMID- 29570627
TI  - Localization of an Underwater Control Network Based on Quasi-Stable Adjustment.
AB  - There exists a common problem in the localization of underwater control networks
      that the precision of the absolute coordinates of known points obtained by marine
      absolute measurement is poor, and it seriously affects the precision of the whole
      network in traditional constraint adjustment. Therefore, considering that the
      precision of underwater baselines is good, we use it to carry out quasi-stable
      adjustment to amend known points before constraint adjustment so that the points
      fit the network shape better. In addition, we add unconstrained adjustment for
      quality control of underwater baselines, the observations of quasi-stable
      adjustment and constrained adjustment, to eliminate the unqualified baselines and
      improve the results' accuracy of the two adjustments. Finally, the modified
      method is applied to a practical LBL (Long Baseline) experiment and obtains a
      mean point location precision of 0.08 m, which improves by 38% compared with the
      traditional method.

PMID- 29570626
TI  - Angiotensin II-Induced Mesangial Cell Damaged Is Preceded by Cell Membrane
      Permeabilization Due to Upregulation of Non-Selective Channels.
AB  - Connexin43 (Cx43), pannexin1 (Panx1) and P2X7 receptor (P2X7R) are expressed in
      kidneys and are known to constitute a feedforward mechanism leading to
      inflammation in other tissues. However, the possible functional relationship
      between these membrane channels and their role in damaged renal cells remain
      unknown. In the present work, we found that MES-13 cells, from a cell line
      derived from mesangial cells, stimulated with angiotensin II (AngII) developed
      oxidative stress (OS, thiobarbituric acid reactive species (TBARS) and generated
      pro-inflammatory cytokines (ELISA; IL-1beta and TNF-alpha). The membrane
      permeability increased progressively several hours before the latter outcome,
      which was a response prevented by Losartan, indicating the involvement of AT1
      receptors. Western blot analysis showed that the amount of phosphorylated MYPT (a
      substrate of RhoA/ROCK) and Cx43 increased progressively and in parallel in cells
      treated with AngII, a response followed by an increase in the amount in Panx1 and
      P2X7R. Greater membrane permeability was partially explained by opening of Cx43
      hemichannels (Cx43 HCs) and Panx1 channels (Panx1 Chs), as well as P2X7Rs
      activation by extracellular ATP, which was presumably released via Cx HCs and
      Panx1 Chs. Additionally, inhibition of RhoA/ROCK blocked the progressive increase
      in membrane permeability, and the remaining response was explained by the other
      non-selective channels. The rise of activity in the RhoA/ROCK-dependent pathway,
      as well as in Cx HCs, P2X7R, and to a minor extent in Panx1 Chs led to higher
      amounts of TBARS and pro-inflammatory cytokines. We propose that AngII-induced
      mesangial cell damage could be effectively inhibited by concomitantly inhibiting
      the RhoA/ROCK-dependent pathway and one or more non-selective channel(s)
      activated through this pathway.

PMID- 29570628
TI  - A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and
      Independent Pruritus.
AB  - Pruriceptive itch originates following activation of peripheral sensory nerve
      terminals when pruritogens come in contact with the skin. The ability of
      botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent
      terminals provides a rationale for studying its effect on pruritus. This study
      investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound
      48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice
      received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14
      and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral
      hind paw scratching was determined using an automated recording device. The
      effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human
      and murine mast cells and the presence of SNAREs was determined using qPCR,
      immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced
      48/80 and CQ induced scratching behavior starting on day 2 with reversal by day
      21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and
      immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells,
      however, Western blots did not. This study demonstrates the long-lasting anti
      pruritic effects of two BoNT serotypes, in a murine pruritus model using two
      different mechanistically driven pruritogens. These data also indicate that BoNTs
      may have a direct effect upon mast cell degranulation.

PMID- 29570629
TI  - Constructing TC-1-GLUC-LMP2 Model Tumor Cells to Evaluate the Anti-Tumor Effects
      of LMP2-Related Vaccines.
AB  - Epstein-Barr virus (EBV) is related to a variety of malignant tumors, and its
      encoded protein, latent membrane protein 2 (LMP2), is an effective target antigen
      that is widely used to construct vector vaccines. However, the model cells
      carrying LMP2 have still not been established to assess the oncolytic effect of
      LMP2-related vaccines at present. In this study, TC-1-GLUC-LMP2 tumor cells were
      constructed as target cells to evaluate the anti-tumor effects of LMP2-assosiated
      vaccines. The results showed that both LMP2 and Gaussia luciferase (GLuc) genes
      could be detected by polymerase chain reaction (PCR) and reverse transcription
      polymerase chain reaction (RT-PCR) in TC-1-GLUC-LMP2 cells. Western blot results
      showed that the LMP2 and Gaussia luciferase proteins were stably expressed in
      tumor cells for at least 30 generations. We mixed 5 * 104 LMP2-specific mouse
      splenic lymphocytes with 5 * 103 TC-1-GLUC-LMP2 target cells and found that the
      target cells were killed as the specific killing effect was obviously enhanced by
      the increased quantities of LMP2-peptide stimulated spleens. Furthermore, the
      tumor cells could not be observed in the mice inoculated TC-1-GLUC-LMP2 cells
      after being immunized with vaccine-LMP2, while the vaccine-NULL immunized mice
      showed that tumor volume gradually grew with increased inoculation time. These
      results indicated that the TC-1-GLUC-LMP2 cells stably expressing LMP2 and GLuc
      produced tumors in mice, and that the LMP2-specific cytotoxic T lymphocyte (CTL)
      effectively killed the cells in vitro and in vivo, suggesting that TC-1-GLUC-LMP2
      cells can be used as model cells to assess the immune and antitumor effects of
      LMP2-related vaccines.

PMID- 29570630
TI  - Synthesis of Alkyl-Glycerolipids Standards for Gas Chromatography Analysis:
      Application for Chimera and Shark Liver Oils.
AB  - Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a
      long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are
      ubiquitously found in different tissues but, are abundant in shark liver oil,
      breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are
      commercially available, while many others with saturated or mono-unsaturated
      alkyl chains of variable length are not available. These compounds are, however,
      necessary as standards for analytical methods. Here, we investigated different
      reported procedures and we adapted some of them to prepare a series of 1-O-alkyl
      glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0,
      17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these
      standards were fully characterized by NMR and GC-MS. Finally, we used these
      standards to identify the AEL subtypes in shark and chimera liver oils. The
      distribution of the identified AEL were: 14:0 (20-24%), 16:0 (42-54%) and 18:1 (6
      16%) and, to a lesser extent, (0.2-2%) for each of the following: 16:1, 17:0,
      18:0, and 20:0. These standards open the possibilities to identify AEL subtypes
      in tumours and compare their composition to those of non-tumour tissues.

PMID- 29570631
TI  - Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven
      by Four Toxin Families.
AB  - Phenotypic diversity generated through altered gene expression is a primary
      mechanism facilitating evolutionary response in natural systems. By linking the
      phenotype to genotype through transcriptomics, it is possible to determine what
      changes are occurring at the molecular level. High phenotypic diversity has been
      documented in rattlesnake venom, which is under strong selection due to its role
      in prey acquisition and defense. Rattlesnake venom can be characterized by the
      presence (Type A) or absence (Type B) of a type of neurotoxic phospholipase A 2
      (PLA 2 ), such as Mojave toxin, that increases venom toxicity. Mojave
      rattlesnakes (Crotalus scutulatus), represent this diversity as both venom types
      are found within this species and within a single panmictic population in the
      Sonoran Desert. We used comparative venom gland transcriptomics of nine specimens
      of C. scutulatus from this region to test whether expression differences explain
      diversity within and between venom types. Type A individuals expressed
      significantly fewer toxins than Type B individuals owing to the diversity of C
      type lectins (CTLs) and snake venom metalloproteinases (SVMPs) found in Type B
      animals. As expected, both subunits of Mojave toxin were exclusively found in
      Type A individuals but we found high diversity in four additional PLA 2 s that
      was not associated with a venom type. Myotoxin a expression and toxin number
      variation was not associated with venom type, and myotoxin a had the highest
      range of expression of any toxin class. Our study represents the most
      comprehensive transcriptomic profile of the venom type dichotomy in rattlesnakes
      and C. scutulatus. Even intra-specifically, Mojave rattlesnakes showcase the
      diversity of snake venoms and illustrate that variation within venom types blurs
      the distinction of the venom dichotomy.

PMID- 29570633
TI  - Magnetron-Sputtered, Biodegradable FeMn Foils: The Influence of Manganese Content
      on Microstructure, Mechanical, Corrosion, and Magnetic Properties.
AB  - FeMn alloys show a great potential for the use as a biodegradable material for
      medical vascular implants. To optimize the material properties, with respect to
      the intended application, new fabrication methods also have to be investigated.
      In this work different Fe-FeMn32 multilayer films were deposited by magnetron
      sputtering. The deposition was done on a substrate structured by UV lithography.
      This technique allows the fabrication of in-situ structured foils. In order to
      investigate the influence of the Mn content on the material properties foils with
      an overall Mn content of 5, 10, 15, and 17 wt % were fabricated. The freestanding
      foils were annealed post-deposition, in order to homogenize them and adjust the
      material properties. The material was characterized in terms of microstructure,
      corrosion, mechanical, and magnetic properties using X-ray diffraction, electron
      microscopy, electrochemical polarization, immersion tests, uniaxial tensile
      tests, and vibrating sample magnetometry. Due to the unique microstructure that
      can be achieved by the fabrication via magnetron sputtering, the annealed foils
      showed a high mechanical yield strength (686-926 MPa) and tensile strength (712
      1147 MPa). Owing the stabilization of the non-ferromagnetic epsilon- and gamma
      phase, it was shown that even Mn concentrations of 15-17 wt % are sufficient to
      distinctly enhance the magnetic resonance imaging (MRI) compatibility of FeMn
      alloys.

PMID- 29570632
TI  - Micro-Economics of Apoptosis in Cancer: ncRNAs Modulation of BCL-2 Family
      Members.
AB  - In the last few years, non-coding RNAs (ncRNAs) have been a hot topic in cancer
      research. Many ncRNAs were found to regulate the apoptotic process and to play a
      role in tumor cell resistance to treatment. The apoptotic program is on the
      frontline as self-defense from cancer onset, and evasion of apoptosis has been
      classified as one of the hallmarks of cancer responsible for therapy failure. The
      B-cell lymphoma 2 (BCL-2) family members are key players in the regulation of
      apoptosis and mediate the activation of the mitochondrial death machinery in
      response to radiation, chemotherapeutic agents and many targeted therapeutics.
      The balance between the pro-survival and the pro-apoptotic BCL-2 proteins is
      strictly controlled by ncRNAs. Here, we highlight the most common mechanisms
      exerted by microRNAs, long non-coding RNAs and circular RNAs on the main
      mediators of the intrinsic apoptotic cascade with particular focus on their
      significance in cancer biology.

PMID- 29570635
TI  - Oxidative Stress and Space Biology: An Organ-Based Approach.
AB  - The environment of space provides many challenges to the human physiology and
      therefore to extended habitation and exploration[...].

PMID- 29570634
TI  - Current Strategies to Enhance Anti-Tumour Immunity.
AB  - The interaction of the immune system with cancer is complex, but new approaches
      are resulting in exciting therapeutic benefits. In order to enhance the immune
      response to cancer, immune therapies seek to either induce high avidity immune
      responses to tumour specific antigens or to convert the tumour to a more pro
      inflammatory microenvironment. Strategies, including vaccination, oncolytic
      viruses, and adoptive cell transfer all seek to induce anti-tumour immunity. To
      overcome the suppressive tumour microenvironment checkpoint inhibitors and
      modulators of regulatory cell populations have been investigated. This review
      summarizes the recent advances in immune therapies and discusses the importance
      of combination therapies in the treatment of cancers.

PMID- 29570637
TI  - Design, Synthesis, and SAR of Novel 2-Glycinamide Cyclohexyl Sulfonamide
      Derivatives against Botrytis cinerea.
AB  - N-(2-trifluoromethyl-4-chlorophenyl)-2-oxocyclohexyl sulfonamide (chesulfamide)
      is in the limelight as a novel fungicide, and has fungicidal activity against
      Botrytis cinerea. For exploring more novel structures, 33 new compounds were
      synthesized by N-alkylation and acid-amine coupling reactions with chesulfamide
      as the core moiety, and their structures were characterized and established by 1H
      NMR, 13C-NMR, MS, and elemental analysis. The structure of (1R,2S)-2-(2-(N-(4
      chloro-2-trifluoromethylphenyl)sulfamoyl)-cyclohexylamino)-N-(2
      trifluoromethylphenyl) acetamide (II-19) was defined by X-ray single crystal
      diffraction. The in vivo and in vitro fungicidal activities against B. cinerea
      were evaluated. The bioassay results of mycelial growth demonstrated that most
      compounds exhibited excellent inhibitory activity against B. cinerea at 50 MUg mL
      1, and 7 compounds showed lower EC50 values than boscalid (EC50 = 4.46 MUg mL-1)
      against B. cinerea (CY-09). In cucumber pot experiment, the inhibitory rates of
      four compounds (II-4, II-5, II-12, and II-13) against B. cinerea were 90.48,
      93.45, 92.86, and 91.07, which were better than cyprodinil (88.69%), the best
      performing of all controls. In tomato pot experiment, the control efficacy of two
      analogs (II-8 and II-15) were 87.98 and 87.97% at 200 MUg mL-1, which were
      significantly higher than boscalid (78.10%). Most compounds have an excellent
      fungicidal effect on B. cinerea, with potential as a lead compound for developing
      new pesticides.

PMID- 29570636
TI  - Encapsulation of Curcumin-Loaded Liposomes for Colonic Drug Delivery in a pH
      Responsive Polymer Cluster Using a pH-Driven and Organic Solvent-Free Process.
AB  - The present study aimed to develop and optimize liposome formulation for the
      colonic delivery of biologically active compounds. A strategy to facilitate such
      targeting is to formulate liposomes with a polymer coating sensitive to the pH
      shifts in the gastrointestinal tract. To this end, liposomes encapsulating
      curcumin-chosen as the biologically active compound model-and coated with the pH
      responsive polymer Eudragit S100 were prepared and characterized. Curcumin was
      encapsulated into small unilamellar vesicles (SUVs) by the micelle-to-vesicle
      transition method (MVT) in a simple and organic solvent-free way. Curcumin-loaded
      liposomes were coated with Eudragit S100 by a fast and easily scalable pH-driven
      method. The prepared liposomes were evaluated for size, surface morphology,
      entrapment efficiency, stability, in vitro drug release, and curcumin antioxidant
      activity. In particular, curcumin-loaded liposomes displayed size lower than 100
      nm, encapsulation efficiency of 98%, high stability at both 4  degrees C and 25 
      degrees C, high in vitro antioxidant activity, and a cumulative release that was
      completed within 200 min. A good Eudragit S100 coating which did not alter the
      properties of the curcumin-loaded liposomes was obtained. The present work
      therefore provides a fast and solvent-free method to prepare pH-responsive
      polymer-coated liposomes for the colonic delivery of biologically active
      compounds.

PMID- 29570638
TI  - The Association between Potential Exposure to Magazine Ads with Voluntary Health
      Warnings and the Perceived Harmfulness of Electronic Nicotine Delivery Systems
      (ENDS).
AB  - (1) Background: Several brands of electronic nicotine delivery systems (ENDS)
      carry voluntary health warning messages. This study examined how potential
      exposure to ENDS magazine ads with these voluntary health warnings were
      associated with the perceived harmfulness of ENDS. (2) Methods: Risk perception
      measures and self-reported exposure to ENDS ads were obtained from the 2014
      Georgia State University (GSU) Tobacco Products and Risk Perceptions Survey of a
      nationally representative sample of U.S. adults. We examined the association
      between potential exposure to magazine ads with warnings and the perceived harms
      of ENDS relative to cigarettes, using binary logistic regressions and controlling
      for general ENDS ad exposure and socio-demographic characteristics. (3) Results:
      Potential exposure to ENDS magazine ads with warnings was associated with a lower
      probability of considering ENDS to be more or equally harmful compared to
      cigarettes, particularly among non-smokers (OR = 0.16; 95% CI: 0.04-0.77). In
      addition, ad exposure, ENDS use history, race/ethnicity, gender, education, and
      income were also associated with harm perceptions. (4) Conclusions: This study
      did not find evidence that magazine ads with warnings increased misperceptions
      that ENDS are equally or more harmful than cigarettes. With more ENDS
      advertisements carrying warnings, more research is needed to determine how the
      warnings in advertisements convey relative harm information to consumers and the
      public.

PMID- 29570640
TI  - Assessment of Potentially Toxic Elements as Non-Point Sources of Contamination in
      the Upper Crocodile Catchment Area, North-West Province, South Africa.
AB  - The concentration of potential toxic elements (PTEs) in the Upper Crocodile river
      catchment area in North-west Province, South Africa, was investigated. Water and
      sediment samples were collected among different land uses in the upper Crocodile
      River catchment area and analysed using inductively-coupled plasma-mass
      spectrometry (ICP-MS). Several guidelines were used to gauge the level of
      contamination and possible toxic effect of PTEs. The physicochemical analysis
      showed that electrical conductivity (EC), pH, and total dissolved solids (TDS)
      values complied with the recommended values of Department of Water and Forestry
      (DWAF) guidelines for South Africa. The average concentration of Cu, Pb, Cd, Zn,
      As, Cr, Al, and Mn in the water samples were lower than the recommended levels
      for water-quality guidelines for aquatic environments except for Fe, which
      exceeded the recommended values of DWAF of 0.1 mg/L and EPA (US) of 0.3 mg/L. The
      level of contamination was measured using the enrichment factor, contamination
      factor, and geoaccumulation index. The level of Cr was above the stipulated
      threshold limit of the sediment quality guideline for adverse biological effects,
      suggesting an ecotoxicology risk of anthropogenic origin, which was confirmed by
      statistical analysis. The non-point sources of PTEs are spatially distributed
      according to land-use types and are strongly correlated to land use.

PMID- 29570639
TI  - 1D Piezoelectric Material Based Nanogenerators: Methods, Materials and Property
      Optimization.
AB  - Due to the enhanced piezoelectric properties, excellent mechanical properties and
      tunable electric properties, one-dimensional (1D) piezoelectric materials have
      shown their promising applications in nanogenerators (NG), sensors, actuators,
      electronic devices etc. To present a clear view about 1D piezoelectric materials,
      this review mainly focuses on the characterization and optimization of the
      piezoelectric properties of 1D nanomaterials, including semiconducting nanowires
      (NWs) with wurtzite and/or zinc blend phases, perovskite NWs and 1D polymers.
      Specifically, the piezoelectric coefficients, performance of single NW-based NG
      and structure-dependent electromechanical properties of 1D nanostructured
      materials can be respectively investigated through piezoresponse force
      microscopy, atomic force microscopy and the in-situ scanning/transmission
      electron microcopy. Along with the introduction of the mechanism and
      piezoelectric properties of 1D semiconductor, perovskite materials and polymers,
      their performance improvement strategies are summarized from the view of
      microstructures, including size-effect, crystal structure, orientation and
      defects. Finally, the extension of 1D piezoelectric materials in field effect
      transistors and optoelectronic devices are simply introduced.

PMID- 29570641
TI  - Micro-Doppler Effect Removal in ISAR Imaging by Promoting Joint Sparsity in Time
      Frequency Domain.
AB  - For micromotion scatterers with small rotating radii, the micro-Doppler (m-D)
      effect interferes with cross-range compression in inverse synthetic aperture
      radar (ISAR) imaging and leads to a blurred main body image. In this paper, a
      novel method is proposed to remove the m-D effect by promoting the joint sparsity
      in the time-frequency domain. Firstly, to obtain the time-frequency
      representations of the limited measurements, the short-time Fourier transform
      (STFT) was modelled by an underdetermined equation. Then, a new objective
      function was used to measure the joint sparsity of the STFT entries so that the
      joint sparse recovery problem could be formulated as a constrained minimization
      problem. Similar to the smoothed l 0 (SL0) algorithm, a steepest descend approach
      was used to minimize the new objective function, where the projection step was
      tailored to make it suitable for m-D effect removal. Finally, we utilized the
      recovered STFT entries to obtain the main body echoes, based on which cross-range
      compression could be realized without m-D interference. After all contaminated
      range cells were processed by the proposed method, a clear main body image could
      be achieved. Experiments using both the point-scattering model and
      electromagnetic (EM) computation validated the performance of the proposed
      method.

PMID- 29570642
TI  - Competitive Deep-Belief Networks for Underwater Acoustic Target Recognition.
AB  - Underwater acoustic target recognition based on ship-radiated noise belongs to
      the small-sample-size recognition problems. A competitive deep-belief network is
      proposed to learn features with more discriminative information from labeled and
      unlabeled samples. The proposed model consists of four stages: (1) A standard
      restricted Boltzmann machine is pretrained using a large number of unlabeled data
      to initialize its parameters; (2) the hidden units are grouped according to
      categories, which provides an initial clustering model for competitive learning;
      (3) competitive training and back-propagation algorithms are used to update the
      parameters to accomplish the task of clustering; (4) by applying layer-wise
      training and supervised fine-tuning, a deep neural network is built to obtain
      features. Experimental results show that the proposed method can achieve
      classification accuracy of 90.89%, which is 8.95% higher than the accuracy
      obtained by the compared methods. In addition, the highest accuracy of our method
      is obtained with fewer features than other methods.

PMID- 29570643
TI  - Stretchable, Flexible, Scalable Smart Skin Sensors for Robotic Position and Force
      Estimation.
AB  - The design and validation of a continuously stretchable and flexible skin sensor
      for collaborative robotic applications is outlined. The skin consists of a PDMS
      skin doped with Carbon Nanotubes and the addition of conductive fabric, connected
      by only five wires to a simple microcontroller. The accuracy is characterized in
      position as well as force, and the skin is also tested under uniaxial stretch.
      There are also two examples of practical implementations in collaborative robotic
      applications. The stationary position estimate has an RMSE of 7.02 mm, and the
      sensor error stays within 2.5 +/- 1.5 mm even under stretch. The skin
      consistently provides an emergency stop command at only 0.5 N of force and is
      shown to maintain a collaboration force of 10 N in a collaborative control
      experiment.

PMID- 29570644
TI  - Effects of Lysozyme on the Activity of Ionic of Fluoroquinolone Species.
AB  - Fluoroquinolones (FQs) constitute an important class of biologically active broad
      spectrum antibacterial drugs that are which are in contact with many biological
      fluids under different acidity conditions. We studied the reactivity of
      ciprofloxacin (Cpx) and levofloxacin (Lev) and their interaction with lysozyme
      (Lyz) at different pH values, using UV-visible absorption, fluorescence, infrared
      spectroscopies supported by DFT calculation and docking. In addition, by
      antimicrobial assays, the biological consequences of the interaction were
      evaluated. DFT calculation predicted that the FQ cationic species present at acid
      pH have lower stabilization energies, with an electric charge rearrangement
      because of their interactions with solvent molecules. NBO and frontier orbital
      calculations evidenced the role of two charged centers, NH2+ and COO-, for
      interactions by electronic delocalization effects. Both FQs bind to Lyz via a
      static quenching with a higher interaction in neutral medium. The interaction
      induces a structural rearrangement in beta-sheet content while in basic pH a
      protective effect against the denaturation of Lyz was inferred. The analysis of
      thermodynamic parameters and docking showed that hydrophobic, electrostatic
      forces and hydrogen bond are the responsible of Cpx-Lyz and Lev-Lyz associations.
      Antimicrobial assays evidenced an antagonist effect of Lyz in acid medium while
      in neutral medium the FQs' activities were not modified by Lyz.

PMID- 29570645
TI  - A Framework to Design the Computational Load Distribution of Wireless Sensor
      Networks in Power Consumption Constrained Environments.
AB  - In this paper, we present a work based on the computational load distribution
      among the homogeneous nodes and the Hub/Sink of Wireless Sensor Networks (WSNs).
      The main contribution of the paper is an early decision support framework helping
      WSN designers to take decisions about computational load distribution for those
      WSNs where power consumption is a key issue (when we refer to "framework" in this
      work, we are considering it as a support tool to make decisions where the
      executive judgment can be included along with the set of mathematical tools of
      the WSN designer; this work shows the need to include the load distribution as an
      integral component of the WSN system for making early decisions regarding energy
      consumption). The framework takes advantage of the idea that balancing sensors
      nodes and Hub/Sink computational load can lead to improved energy consumption for
      the whole or at least the battery-powered nodes of the WSN. The approach is not
      trivial and it takes into account related issues such as the required data
      distribution, nodes, and Hub/Sink connectivity and availability due to their
      connectivity features and duty-cycle. For a practical demonstration, the proposed
      framework is applied to an agriculture case study, a sector very relevant in our
      region. In this kind of rural context, distances, low costs due to vegetable
      selling prices and the lack of continuous power supplies may lead to viable or
      inviable sensing solutions for the farmers. The proposed framework systematize
      and facilitates WSN designers the required complex calculations taking into
      account the most relevant variables regarding power consumption, avoiding
      full/partial/prototype implementations, and measurements of different
      computational load distribution potential solutions for a specific WSN.

PMID- 29570646
TI  - Preparation of Flame Retardant Polyacrylonitrile Fabric Based on Sol-Gel and
      Layer-by-Layer Assembly.
AB  - This paper aims to develop a novel method, i.e., sol-gel combined with layer-by
      layer assembly technology, to impart flame retardancy on polyacrylonitrile (PAN)
      fabrics. Silica-sol was synthesized via the sol-gel process and acted as cationic
      solution, and phytic acid (PA) was used as the anionic medium. Flame-retardant
      treated PAN fabric (FR-PAN) could achieve excellent flame retardancy with 10
      bilayer (10BL) coating through layer-by-layer assembly. The structure of the
      fabrics was characterized by X-ray photoelectron spectroscopy (XPS) and Fourier
      transform infrared spectroscopy (FTIR). The thermal stability and flame
      retardancy were evaluated by thermogravimetric (TG) analysis, cone calorimetry
      (CC) and limiting oxygen index (LOI). The LOI value of the coated fabric was up
      to 33.2 vol % and the char residue at 800  degrees C also increased to 57 wt %.
      Cone calorimetry tests revealed that, compared to the control fabric, the peak of
      heat release rate (PHRR) and total heat release (THR) of FR-PAN decreased by 66%
      and 73%, respectively. These results indicated that sol-gel combined with layer
      by-layer assembly technique could impart PAN fabric with satisfactory flame
      retardant properties, showing an efficient flame retardant strategy for PAN
      fabric.

PMID- 29570647
TI  - Identification, Characterization, and Expression Analysis of a FMRFamide-Like
      Peptide Gene in the Common Chinese Cuttlefish (Sepiella japonica).
AB  - The peptide FMRFamide is one of the well-known peptides involved in multiple
      physiological processes in the phylum Mollusca. In this study, a FMRFamide gene
      (GenBank accession No. KJ933411) was identified in a cuttlefish species called
      Sepiella japonica and was designated as SjFMRFamide. The total length of the
      SjFMRFamide sequence was found to be 1880 bp while the open reading frame
      contained 996 bp encoding a protein of 331 amino acid residues with a predicted
      isoelectric point (pI) and molecular weight (MW) of 9.18 and 38.8 kDa along with
      a 333 bp 5'-untranslated region (UTR) and 551 bp 3'-UTR. The deduced SjFMRFamide
      precursor protein contains one signal peptide and expresses four kinds FMRFamide
      related peptides including a single copy of FLRFamide, ALSGDAFLRFamide, and
      FIRFamide and multiple copies of FMRFamide. Results of phylogenetic relation
      analysis strongly indicated that the sequence of this gene shares high identity
      with the genes of known FMRFamides. Spatial expression analysis indicated the
      highest mRNA expression of SjFMRFamide in the brain of male and female
      cuttlefishes among the eight tissues analyzed. An in situ hybridization assay of
      the brain indicated that SjFMRFamide was transcribed in several functional lobes,
      which suggests that it might be related to many physiological regulatory
      mechanisms. This is the first study describing FMRFamide in S. japonica and the
      results may contribute to future studies of neuropeptide evolution or may prove
      useful for the development of aquaculture methods for this cuttlefish species.

PMID- 29570648
TI  - Potential of Cellulose Functionalized with Carboxylic Acid as Biosorbent for the
      Removal of Cationic Dyes in Aqueous Solution.
AB  - In the last decade, adsorption has been used to minimize the pollution caused by
      dyes, which represents a serious environmental problem. In this context, this
      work reports the preparation of phthalic anhydride-modified cellulose (PhCel),
      through the reaction of cellulose (Cel) with phthalic anhydride (Ph). The
      efficiency of the reaction was observed by elemental analysis, Fourier Transform
      Infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and
      thermogravimetry/derivative thermogravimetry (TG/DTG). The adsorbent matrix (Cel
      and PhCel) was used in the removal of crystal violet (CV) and methylene blue (MB)
      dyes in aqueous medium. In the kinetic study, the experimental data obtained had
      the best fit to the pseudo-first-order model. In general, the isotherms obtained
      at different temperatures had a best fit to the model proposed by Langmuir, and
      the CV and MB adsorption process in adsorbent matrixes can be favored strictly by
      hydrogen bonds and/or electrostatic interactions for Cel and electrostatic
      interactions for PhCel.

PMID- 29570649
TI  - Investigating the Interaction of Ascorbic Acid with Anthocyanins and
      Pyranoanthocyanins.
AB  - Juices colored by anthocyanins experience color loss related to fortification
      with ascorbic acid (AA), thought to be the result of condensation at Carbon-4 of
      anthocyanins. To further understand this mechanism, pyranoanthocyanins, having a
      fourth-ring covalently occupying Carbon-4, were synthesized to compare its
      reactivity with AA against that of anthocyanins. Pyranoanthocyanins were
      synthesized by combining chokeberry anthocyanins with pyruvic acid. AA (250-1000
      mg/L) was added to either chokeberry extract, cyanidin-3-galactoside, or 5
      Carboxypyranocyanidin-3-galactoside. Samples were stored in the dark for 5 days
      at 25  degrees C and spectra (380-700 nm), color (CIE-L*c*h*), and composition
      changes (HPLC-MS/MS) were monitored. Extensive bleaching occurred for cyanidin-3
      galactoside and chokeberry colored solutions, with a decrease in half-lives from
      22.8 to 0.3 days for Cyanidin-3-galactoside when 1000 mg/L AA was added. 5
      Carboxypyranocyanidin-3-galactoside solution better maintained color with limited
      loss in absorbance, due to the formation of colored degradation products
      (lambdavis-max = 477 to 487 nm), and half-life decrease from 40.8 to 2.7 days, an
      8-13-fold improvement compared to anthocyanins. This suggested alternative sites
      of reactivity with AA. Carbon-4 may be the preferred site for AA-pigment
      interactions, but it was not the only location. With Carbon-4 blocked, 5
      Carboxypyranocyanidin-3-galactoside reacted with AA to form new pigments and
      reduce bleaching.

PMID- 29570650
TI  - A Review of Mechanoluminescence in Inorganic Solids: Compounds, Mechanisms,
      Models and Applications.
AB  - Mechanoluminescence (ML) is the non-thermal emission of light as a response to
      mechanical stimuli on a solid material. While this phenomenon has been observed
      for a long time when breaking certain materials, it is now being extensively
      explored, especially since the discovery of non-destructive ML upon elastic
      deformation. A great number of materials have already been identified as
      mechanoluminescent, but novel ones with colour tunability and improved
      sensitivity are still urgently needed. The physical origin of the phenomenon,
      which mainly involves the release of trapped carriers at defects with the help of
      stress, still remains unclear. This in turn hinders a deeper research, either
      theoretically or application oriented. In this review paper, we have tabulated
      the known ML compounds according to their structure prototypes based on the
      connectivity of anion polyhedra, highlighting structural features, such as
      framework distortion, layered structure, elastic anisotropy and microstructures,
      which are very relevant to the ML process. We then review the various proposed
      mechanisms and corresponding mathematical models. We comment on their
      contribution to a clearer understanding of the ML phenomenon and on the derived
      guidelines for improving properties of ML phosphors. Proven and potential
      applications of ML in various fields, such as stress field sensing, light
      sources, and sensing electric (magnetic) fields, are summarized. Finally, we
      point out the challenges and future directions in this active and emerging field
      of luminescence research.

PMID- 29570651
TI  - Unique Collagen Fibers for Biomedical Applications.
AB  - The challenge to develop grafts for tissue regeneration lies in the need to
      obtain a scaffold that will promote cell growth in order to form new tissue at a
      trauma-damaged site. Scaffolds also need to provide compatible mechanical
      properties that will support the new tissue and facilitate the desired
      physiological activity. Here, we used natural materials to develop a bio
      composite made of unique collagen embedded in an alginate hydrogel material. The
      collagen fibers used to create the building blocks exhibited a unique hyper
      elastic behavior similar to that of natural human tissue. The prominent
      mechanical properties, along with the support of cell adhesion affects cell shape
      and supports their proliferation, consequently facilitating the formation of a
      new tissue-like structure. The current study elaborates on these unique collagen
      fibers, focusing on their structure and biocompatibility, in an in vitro model.
      The findings suggest it as a highly appropriate material for biomedical
      applications. The promising in vitro results indicate that the distinctive
      collagen fibers could serve as a scaffold that can be adapted for tissue
      regeneration, in support of healing processes, along with maintaining tissue
      mechanical properties for the new regenerate tissue formation.

PMID- 29570652
TI  - GC-MS Based Metabolomics and NMR Spectroscopy Investigation of Food Intake
      Biomarkers for Milk and Cheese in Serum of Healthy Humans.
AB  - The identification and validation of food intake biomarkers (FIBs) in human
      biofluids is a key objective for the evaluation of dietary intake. We report here
      the analysis of the GC-MS and 1H-NMR metabolomes of serum samples from a
      randomized cross-over study in 11 healthy volunteers having consumed isocaloric
      amounts of milk, cheese, and a soy drink as non-dairy alternative. Serum was
      collected at baseline, postprandially up to 6 h, and 24 h after consumption. A
      multivariate analysis of the untargeted serum metabolomes, combined with a
      targeted analysis of candidate FIBs previously reported in urine samples from the
      same study, identified galactitol, galactonate, and galactono-1,5-lactone (milk),
      3-phenyllactic acid (cheese), and pinitol (soy drink) as candidate FIBs for these
      products. Serum metabolites not previously identified in the urine samples, e.g.,
      3-hydroxyisobutyrate after cheese intake, were detected. Finally, an analysis of
      the postprandial behavior of candidate FIBs, in particular the dairy fatty acids
      pentadecanoic acid and heptadecanoic acid, revealed specific kinetic patterns of
      relevance to their detection in future validation studies. Taken together,
      promising candidate FIBs for dairy intake appear to be lactose and metabolites
      thereof, for lactose-containing products, and microbial metabolites derived from
      amino acids, for fermented dairy products such as cheese.

PMID- 29570653
TI  - Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting
      Chemicals and Mycotoxins through Stable Isotope Techniques.
AB  - Multiple drivers of the double burden of malnutrition (DBM) include a rapid shift
      from predominantly plant-based diets to energy-dense foods based on meats, milk,
      animal fats and vegetable oils. The shift to overweight and obesity is driven by
      increased exposure to mass media, urbanization, technological advances in food
      processing, rising income and increased population density associated with
      increased access to cheap foods. At the same time, undernutrition persists mainly
      due to food insecurity and lack of access to safe water, sanitation and adequate
      health care. All known nutrition interventions result in only one third reduction
      in stunting. Little consideration has been given to hazardous exposure to
      endocrine disrupting chemicals (EDCs) and microbial toxins as major components of
      the malnutrition-causal framework. These hazards include microbial toxins, for
      example, mycotoxins, and environmental pollutants such as persistent organic
      pollutants (POPs), some of which are known to disrupt the endocrine system. These
      hazards sit at the cross road of undernutrition and overweight and obesity since
      the exposure cuts across the critical window of opportunity (the first 1000
      days). In this review, we update on the role of food and environmental
      contaminants, especially EDCs and aflatoxins, in child growth and on the
      implications for metabolic dysfunction and disease risk in later life, and
      discuss potential applications of nuclear and isotopic techniques to elucidate
      the underlying biological mechanisms, outcome indicators, as well as occurrence
      levels.

PMID- 29570654
TI  - Immunomolecular Characterization of MIC-1, a Novel Antigen in Babesia bigemina,
      Which Contains Conserved and Immunodominant B-Cell Epitopes that Induce
      Neutralizing Antibodies.
AB  - Babesia bigemina is one of the most prevalent species causing bovine babesiosis
      around the world. Antigens involved in host cell invasion are vaccine targets for
      this disease but are largely unknown in this species. The invasion process of
      Babesia spp. into erythrocytes involves membrane proteins from the apical
      complex. A protein stored in the micronemes, called Micronemal Protein 1 (MIC-1),
      contains a sialic acid binding domain that participates in the invasion process
      of host cells and is a vaccine candidate in other apicomplexan parasites. It is
      not known if there is a homologous gene for mic-1 in B. bigemina. Therefore, the
      aim of this study was to characterize the mic-1 gene homologue in Babesia
      bigemina. A gene was found with a microneme adhesive repeat (MAR) domain in the
      predicted amino acid sequence. Transcription was determined by reverse
      transcription polymerase chain reaction (RT-PCR). Subsequently, antibodies
      against peptides containing conserved B-cell epitopes were used to confirm the
      expression of MIC-1 in intraerythrocytic merozoites. The presence of anti MIC-1
      antibodies in cattle naturally infected with B. bigemina was determined and up to
      97.4% of the cattle sera (113 out of 116) identified MIC-1 using enzyme-linked
      immunosorbent assay (ELISA) methods. Finally, antibodies against MIC-1 were able
      to block 70% merozoite invasion in-vitro.

PMID- 29570655
TI  - Population Dynamics of Off-Host Rhipicephalus (Boophilus) microplus (Acari:
      Ixodidae) Larvae in Response to Habitat and Seasonality in South Texas.
AB  - The cattle tick, Rhipicephalus microplus (Canestrini), is an economically
      destructive arthropod because of its ability to vector bovine babesiosis. It is
      known that cattle ticks can spend 80-90% of their lifecycle as questing larvae,
      yet the effect of climatic factors on their off-host behavior and survival is
      unclear. The goal of this study was to measure the effects of specific ecological
      factors on off-host questing larvae in nature. The study was conducted in a south
      Texas pasture over a two-year period, during which time larval populations were
      surveyed. Simultaneously, weather variables-precipitation, relative humidity, and
      ambient temperatures-were recorded. Larval survival rates varied among seasons,
      with the overall highest populations recorded in the spring and the lowest in the
      fall by a ratio of 20:1. In the winter, the larger numbers were collected from
      exposed habitats at a ratio of 6:1. Conversely, canopied habitats in the summer
      had 10-fold larger larval numbers. In the spring, exposed and canopied habitats
      showed no difference in tick larval survival rates. The results show that the
      interaction between season and habitat strongly influence off-host questing tick
      survival. Relative humidity was a key weather variable.

PMID- 29570656
TI  - Educating the Future of Science and Medicine.
AB  - For the past two decades, veterinary educators have been at the forefront of
      innovations in educational practices related to science and medicine. Many of the
      resulting methods have been translated and implemented as best practices across
      the breadth of disciplines in higher education. However, past World Organization
      for Animal Health (OIE) global conferences have highlighted the necessity for
      improving global harmonization of veterinary medical education. This underscores
      a growing need for even broader dissemination of best practices and assessment
      programs related to educating our veterinary workforce.

PMID- 29570657
TI  - Operationalizing Principle-Based Standards for Animal Welfare-Indicators for
      Climate Problems in Pig Houses.
AB  - The Dutch animal welfare law includes so-called principle-based standards. This
      means that the objective is described in abstract terms, enabling farmers to
      comply with the law in their own way. Principle-based standards are, however,
      difficult for the inspection agency to enforce because strict limits are missing.
      This pilot project aimed at developing indicators (measurements) to assess the
      climate in pig houses, thus enabling the enforcement of principle-based
      standards. In total, 64 farms with weaners and 32 farms with growing-finishing
      pigs were visited. On each farm, a set of climate-related measurements was
      collected in six pens. For each of these measurements, a threshold value was set,
      and exceeding this threshold indicated a welfare risk. Farm inspections were
      carried out during winter and spring, thus excluding situations with heat stress.
      Assessment of the variation and correlation between measurements reduced the
      dataset from 39 to 12 measurements. Using a principal components analysis helped
      to select five major measurements as warning signals. The number of exceeded
      thresholds per pen and per farm was calculated for both the large (12) and small
      (five) sets of measurements. CO2 and NH3 concentrations were related to the
      outside temperature. On colder days, there was less ventilation, and thus CO2 and
      NH3 concentrations increased. Air quality, reflected in the CO2 and NH3
      concentrations, was associated with respiratory problems. Eye scores were
      positively correlated with both pig and pen fouling, and pig and pen fouling were
      closely related. We selected five signal indicators: CO2, NH3, and tail and eye
      score for weaners and finishers, and added ear score for weaners and pig fouling
      for growing-finishing pigs. The results indicate that pig farms can be ranked
      based on five signal indicators related to reduced animal welfare caused by
      climatic conditions. This approach could be adopted to other principle-based
      standards for pigs as well as for other species.

PMID- 29570658
TI  - Mechanism of Mercury Adsorption and Oxidation by Oxygen over the CeO2 (111)
      Surface: A DFT Study.
AB  - CeO2 is a promising catalytic oxidation material for flue gas mercury removal.
      Density functional theory (DFT) calculations and periodic slab models are
      employed to investigate mercury adsorption and oxidation by oxygen over the CeO2
      (111) surface. DFT calculations indicate that Hg0 is physically adsorbed on the
      CeO2 (111) surface and the Hg atom interacts strongly with the surface Ce atom
      according to the partial density of states (PDOS) analysis, whereas, HgO is
      adsorbed on the CeO2 (111) surface in a chemisorption manner, with its adsorption
      energy in the range of 69.9-198.37 kJ/mol. Depending on the adsorption methods of
      Hg0 and HgO, three reaction pathways (pathways I, II, and III) of Hg0 oxidation
      by oxygen are proposed. Pathway I is the most likely oxidation route on the CeO2
      (111) surface due to it having the lowest energy barrier of 20.7 kJ/mol. The
      formation of the HgO molecule is the rate-determining step, which is also the
      only energy barrier of the entire process. Compared with energy barriers of Hg0
      oxidation on the other catalytic materials, CeO2 is more efficient at mercury
      removal in flue gas owing to its low energy barrier.

PMID- 29570660
TI  - Effect of Par Frying on Composition and Texture of Breaded and Battered Catfish.
AB  - Catfish is often consumed as a breaded and battered fried product; however, there
      is increasing interest in breaded and battered baked products as a healthier
      alternative. Par frying can improve the texture properties of breaded and
      battered baked products, but there are concerns about the increase in lipid
      uptake from par frying. The objective of this study was to examine the effect of
      different batters (rice, corn, and wheat) and the effect of par frying on the
      composition and texture properties of baked catfish. Catfish fillets were cut
      strips and then coated with batters, which had similar viscosities. Half of the
      strips were par fried in 177  degrees C vegetable oil for 1 min and the other
      half were not par fried. Samples were baked at 177  degrees C for 25 min.
      Analysis included % batter adhesion, cooking loss, protein, lipid, ash, and
      moisture, plus hardness and fracture quality measured using a texture analyzer. A
      trained sensory panel evaluated both breading and flesh texture attributes.
      Results found the lipid content of par fried treatments were significantly higher
      for both corn and wheat batters than for non-par fried treatments. Sensory
      analysis indicated that the texture of the coatings in the par fried treatments
      were significantly greater for hardness attributes. Fillet flakiness was
      significantly greater in the par fried treatments and corn-based batters had
      moister fillet strips compared to the wheat flour batters. Texture analyzer
      hardness values were higher for the par fried treatments.

PMID- 29570659
TI  - Towards Improvements for Penetrating the Blood-Brain Barrier-Recent Progress from
      a Material and Pharmaceutical Perspective.
AB  - The blood-brain barrier (BBB) is a critical biological structure that prevents
      damage to the brain and maintains its bathing microenvironment. However, this
      barrier is also the obstacle to deliver beneficial drugs to treat CNS (central
      nervous system) diseases. Many efforts have been made for improvement of
      delivering drugs across the BBB in recent years to treat CNS diseases. In this
      review, the anatomical and functional structure of the BBB is comprehensively
      discussed. The mechanisms of BBB penetration are summarized, and the methods and
      effects on increasing BBB permeability are investigated in detail. It also
      elaborates on the physical, chemical, biological and nanocarrier aspects to
      improve drug delivery penetration to the brain and introduces some specific drug
      delivery effects on BBB permeability.

PMID- 29570661
TI  - How Long Are Cancer Patients Waiting for Oncological Therapy in Poland?
AB  - BACKGROUND: The five-year relative survival rate in Poland is approximately 10%
      lower compared with the average for Europe. One of the factors that may
      contribute to the inferior treatment results in Poland could be the long time
      between cancer suspicion and the beginning of treatment. The aim of the study was
      to determine the real waiting time for cancer diagnosis and treatment in Poland.
      METHODS: The study was carried out in six cancer centers on a group of 1373
      patients, using a questionnaire to interview patients. The median waiting time
      was estimated as follows: (A) from suspicion (the date of the first visit, with
      symptoms, to a doctor or a preventive or screening test) until histopathological
      diagnosis; (B) from suspicion until initial treatment; and (C) from diagnosis
      until initial treatment. RESULTS: The median times from suspicion to treatment,
      from suspicion to diagnosis, and from diagnosis to treatment, were 10.6, 5.6, and
      5.0 weeks, respectively. Using multivariate analysis, the strongest influence was
      estimated, in a case of tumor localization, to be the method of initial treatment
      and facilities. CONCLUSION: The waiting time for cancer treatment in Poland is
      too long. The highest influence on waiting time was determined, in the case of
      tumors, as the type of cancer and factors related to the health care system.

PMID- 29570662
TI  - Physical Practice and Wellness Courses Reduce Distress and Improve Wellbeing in
      Police Officers.
AB  - BACKGROUND: The aim of this work was to evaluate a course to reduce distress in
      an Italian police force. Based on the findings from the first investigations on
      this population, courses to improve the ability to manage distress were tailored
      by management. Several free courses were proposed, including physical efficiency
      (e.g., total body conditioning) and wellness (e.g., autogenic training) classes.
      The goal of this research was to evaluate the courses and their impact on the
      perceived distress and general health of the participants, as well as the
      effectiveness in increasing the use of adaptive coping strategies. METHODS: A
      descriptive investigation was conducted involving a sample of 105 police officers
      before (time 1) and after (time 2) they had participated in the courses. RESULTS:
      Findings confirmed both physical and wellness courses affected, in participants,
      the perceived distress, thereby increasing the perception of wellbeing. The
      participants expressed having mental health benefits, the use of adaptive coping
      strategies increased, while the maladaptive coping strategies decreased.
      CONCLUSION: This study confirms that these courses could effectively reduce the
      risk of chronic disease, a consequence of persistent exposure to distress.

PMID- 29570663
TI  - Investigating the Effect of Personality, Internet Literacy, and Use Expectancies
      in Internet-Use Disorder: A Comparative Study between China and Germany.
AB  - Research on Internet-use Disorder (IUD) has increased rapidly, indicating its
      clinical and global importance. Past studies suggested cultural diversity
      regarding the prevalence of an IUD, e.g., between Asian and European countries.
      Additionally, it was found that personality factors, Internet-related cognitions
      and specific competences seem to influence IUD tendencies, but research lacks in
      cultural comparative studies regarding these mechanisms. This study focuses on
      differences between Germany and China regarding the above-mentioned
      characteristics. German (n = 411; M = 20.70 years, SD = 3.34 years) and Chinese
      participants (n = 410; M = 20.72 years, SD = 2.65 years) answered the short
      Internet Addiction Test, Big Five Inventories, the Internet-use Expectancies
      Scale, as well as the Internet Literacy Questionnaire. The results revealed
      higher occurrence of IUD symptoms in China. Furthermore, Chinese participants
      scored significantly higher on neuroticism and agreeableness, whereas German
      participants scored higher on extraversion and openness. Compared to German
      participants, Chinese showed higher expectancies to avoid negative feelings
      online and to be positively reinforced. Regarding Internet literacy, German
      participants indicated higher skills concerning the reflection and critical
      analysis of online content, whereas Chinese showed higher expertise in producing
      and interacting online. Further, simple slope analyses indicated that certain
      Internet literacy domains were related differentially to IUD symptoms in Germany
      and China. While Chinese participants with higher reflective skills indicated
      highest IUD symptoms, reflective skills revealed no effect in Germany.
      Additionally, higher self-regulative skills correlated with lower IUD symptoms in
      the German, but not in the Chinese sample. The results give a hint to potential
      cultural differences regarding IUD, especially on the predictive and protective
      role of Internet literacy domains.

PMID- 29570664
TI  - Mortality and Morbidity during Extreme Heat Events and Prevalence of Outdoor
      Work: An Analysis of Community-Level Data from Los Angeles County, California.
AB  - Heat is a well-recognized hazard for workers in many outdoor settings, yet few
      investigations have compared the prevalence of outdoor work at the community
      level and rates of heat-related mortality and morbidity. This analysis examines
      whether heat-related health outcomes occur more frequently in communities with
      higher proportions of residents working in construction, agriculture, and other
      outdoor industries. Using 2005-2010 data from Los Angeles County, California, we
      analyze associations between community-level rates of deaths, emergency
      department (ED) visits, and hospitalizations during summer heat events and the
      prevalence of outdoor work. We find generally higher rates of heat-related ED
      visits and hospitalizations during summer heat events in communities with more
      residents working outdoors. Specifically, each percentage increase in residents
      working in construction resulted in an 8.1 percent increase in heat-related ED
      visits and a 7.9 percent increase in heat-related hospitalizations, while each
      percentage increase in residents working in agriculture and related sectors
      resulted in a 10.9 percent increase in heat-related ED visits. The findings
      suggest that outdoor work may significantly influence the overall burden of heat
      related morbidity at the community level. Public health professionals and
      healthcare providers should recognize work and employment as significant heat
      risk factors when preparing for and responding to extreme heat events.

PMID- 29570666
TI  - A Whole Germline BRCA2 Gene Deletion: How to Learn from CNV In Silico Analysis.
AB  - BRCA1/2 screening in Hereditary Breast and Ovarian Syndrome (HBOC) is an
      essential step for effective patients' management. Next-Generation Sequencing
      (NGS) can rapidly provide high throughput and reliable information about the
      qualitative and quantitative status of tumor-associated genes. Straightforwardly,
      bioinformatics methods play a key role in molecular diagnostics pipelines.
      BRCA1/2 genes were evaluated with our NGS workflow, coupled with Multiplex
      Amplicon Quantification (MAQ) and Multiplex Ligation-dependent Probe
      Amplification (MLPA) assays. Variant calling was performed on Amplicon Suite,
      while Copy Number Variant (CNV) prediction by in house and commercial CNV tools,
      before confirmatory MAQ/MLPA testing. The germline profile of BRCA genes revealed
      a unique HBOC pattern. Although variant calling analysis pinpointed heterozygote
      and homozygote polymorphisms on BRCA1 and BRCA2, respectively, the CNV predicted
      by our script suggested two conflicting interpretations: BRCA1 duplication and/or
      BRCA2 deletion. Our commercial software reported a BRCA1 duplication, in contrast
      with variant calling results. Finally, the MAQ/MLPA assays assessed a whole BRCA2
      copy loss. In silico CNV analysis is a time and cost-saving procedure to
      powerfully identify possible Large Rearrangements using robust and efficient NGS
      pipelines. Our layout shows as bioinformatics algorithms alone cannot completely
      and correctly identify whole BRCA1/2 deletions/duplications. In particular, the
      complete deletion of an entire gene, like in our case, cannot be solved without
      alternative strategies as MLPA/MAQ. These findings support the crucial role of
      bioinformatics in deciphering pitfalls within NGS data analysis.

PMID- 29570665
TI  - Compressive Force Spectroscopy: From Living Cells to Single Proteins.
AB  - One of the most successful applications of atomic force microscopy (AFM) in
      biology involves monitoring the effect of force on single biological molecules,
      often referred to as force spectroscopy. Such studies generally entail the
      application of pulling forces of different magnitudes and velocities upon
      individual molecules to resolve individualistic unfolding/separation pathways and
      the quantification of the force-dependent rate constants. However, a less
      recognized variation of this method, the application of compressive force,
      actually pre-dates many of these "tensile" force spectroscopic studies. Further,
      beyond being limited to the study of single molecules, these compressive force
      spectroscopic investigations have spanned samples as large as living cells to
      smaller, multi-molecular complexes such as viruses down to single protein
      molecules. Correspondingly, these studies have enabled the detailed
      characterization of individual cell states, subtle differences between seemingly
      identical viral structures, as well as the quantification of rate constants of
      functionally important, structural transitions in single proteins. Here, we
      briefly review some of the recent achievements that have been obtained with
      compressive force spectroscopy using AFM and highlight exciting areas of its
      future development.

PMID- 29570667
TI  - Differential Tissue Fatty Acids Profiling between Colorectal Cancer Patients with
      and without Synchronous Metastasis.
AB  - The early detection of colorectal cancer and determination of its metastatic
      potential are important factors to set up more efficacious therapeutic
      strategies. In the present study, we hypothesize that fatty acids analysis in
      colorectal cancer patients can discriminate between metastatic and non-metastatic
      patients. Fifty-one consecutive patients with histologically proven colorectal
      cancer were enrolled in the study and the presence of synchronous metastasis was
      detected in 25 of these 51 patients. Fatty acid profile analysis in red blood
      cell membranes was not able to discriminate the metastatic colorectal cancer
      patients from those without metastasis. However, significant differences in the
      tumor tissue fatty acid profile were found in metastatic cancer patients when
      compared to patients without metastasis. Metastatic patients showed significantly
      lower percentages of Eicosapentaenoic acid (EPA) and higher levels of gamma
      linolenic acid (GLA), a n-3- and n-6-Polyunsaturated fatty acid (PUFA),
      respectively. Our findings, suggesting that membrane lipid rearrangement could
      influence the cellular function and make the cell more prone to metastasis, offer
      the opportunity to develop nutritional strategies that may be helpful in the
      prevention and treatment of colorectal cancer.

PMID- 29570668
TI  - Roles of Chloroplast Retrograde Signals and Ion Transport in Plant Drought
      Tolerance.
AB  - Worldwide, drought affects crop yields; therefore, understanding plants'
      strategies to adapt to drought is critical. Chloroplasts are key regulators of
      plant responses, and signals from chloroplasts also regulate nuclear gene
      expression during drought. However, the interactions between chloroplast
      initiated retrograde signals and ion channels under stress are still not clear.
      In this review, we summarise the retrograde signals that participate in
      regulating plant stress tolerance. We compare chloroplastic transporters that
      modulate retrograde signalling through retrograde biosynthesis or as critical
      components in retrograde signalling. We also discuss the roles of important
      plasma membrane and tonoplast ion transporters that are involved in regulating
      stomatal movement. We propose how retrograde signals interact with ion
      transporters under stress.

PMID- 29570670
TI  - Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38
      MAPK and NF-kappaB Pathways.
AB  - Oxymatrine (OMT) is a strong immunosuppressive agent that has been used in the
      clinic for many years. In the present study, by using plaque inhibition,
      luciferase reporter plasmids, qRT-PCR, western blotting, and ELISA assays, we
      have investigated the effect and mechanism of OMT on influenza A virus (IAV)
      replication and IAV-induced inflammation in vitro and in vivo. The results showed
      that OMT had excellent anti-IAV activity on eight IAV strains in vitro. OMT could
      significantly decrease the promoter activity of TLR3, TLR4, TLR7, MyD88, and
      TRAF6 genes, inhibit IAV-induced activations of Akt, ERK1/2, p38 MAPK, and NF
      kappaB pathways, and suppress the expressions of inflammatory cytokines and MMP
      2/-9. Activators of TLR4, p38 MAPK and NF-kappaB pathways could significantly
      antagonize the anti-IAV activity of OMT in vitro, including IAV replication and
      IAV-induced cytopathogenic effect (CPE). Furthermore, OMT could reduce the loss
      of body weight, significantly increase the survival rate of IAV-infected mice,
      decrease the lung index, pulmonary inflammation and lung viral titter, and
      improve pulmonary histopathological changes. In conclusion, OMT possesses anti
      IAV and anti-inflammatory activities, the mechanism of action may be linked to
      its ability to inhibit IAV-induced activations of TLR4, p38 MAPK, and NF-kappaB
      pathways.

PMID- 29570671
TI  - St. John's Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast
      Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway.
AB  - St. John's Wort (SJW) has been used as an estrogen agonist in the systems
      affected by menopause. Also, hypericin, a bioactive compound of SJW, has been
      used as a photosensitizer in photodynamic therapy. In the present study, we
      investigate the anti-proliferative and pro-apoptotic effects of SJW to
      demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cells
      were cultured with DMSO or various concentrations of SJW ethanol extract (SJWE).
      Cell viability, proliferation, apoptosis, the expression of proteins involved in
      cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose
      dependently suppressed cell growth and induced apoptosis of MCF-7 cells.
      Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein
      kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p
      mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1
      (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and
      showed increases in the expression of pro-apoptotic proteins Bax and Bad with
      decreases in the expression of anti-apoptotic proteins including B-cell lymphoma
      2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death
      promoter (p-Bad). SJWE at 50 MUg/mL showed markedly enhanced caspase-7
      activation. Taken together, our results provide evidence that SJWE shows anti
      proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and
      activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo
      preventive agent without photo-activation.

PMID- 29570669
TI  - State-of-the-Art Fluorescence Fluctuation-Based Spectroscopic Techniques for the
      Study of Protein Aggregation.
AB  - Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS),
      Alzheimer's disease, Parkinson's disease, and Huntington's disease, are
      devastating proteinopathies with misfolded protein aggregates accumulating in
      neuronal cells. Inclusion bodies of protein aggregates are frequently observed in
      the neuronal cells of patients. Investigation of the underlying causes of
      neurodegeneration requires the establishment and selection of appropriate
      methodologies for detailed investigation of the state and conformation of protein
      aggregates. In the current review, we present an overview of the principles and
      application of several methodologies used for the elucidation of protein
      aggregation, specifically ones based on determination of fluctuations of
      fluorescence. The discussed methods include fluorescence correlation spectroscopy
      (FCS), imaging FCS, image correlation spectroscopy (ICS), photobleaching ICS
      (pbICS), number and brightness (N&B) analysis, super-resolution optical
      fluctuation imaging (SOFI), and transient state (TRAST) monitoring spectroscopy.
      Some of these methodologies are classical protein aggregation analyses, while
      others are not yet widely used. Collectively, the methods presented here should
      help the future development of research not only into protein aggregation but
      also neurodegenerative diseases.

PMID- 29570672
TI  - Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and
      Systemic Blood Pressure in Mice.
AB  - Nitric oxide (NO) modulates renal blood flow (RBF) and kidney function and is
      involved in blood pressure (BP) regulation predominantly via stimulation of the
      NO-sensitive guanylyl cyclase (NO-GC), existing in two isoforms, NO-GC1 and NO
      GC2. Here, we used isoform-specific knockout (KO) mice and investigated their
      contribution to renal hemodynamics under normotensive and angiotensin II-induced
      hypertensive conditions. Stimulation of the NO-GCs by S-nitrosoglutathione (GSNO)
      reduced BP in normotensive and hypertensive wildtype (WT) and NO-GC2-KO mice more
      efficiently than in NO-GC1-KO. NO-induced increase of RBF in normotensive mice
      did not differ between the genotypes, but the respective increase under
      hypertensive conditions was impaired in NO-GC1-KO. Similarly, inhibition of
      endogenous NO increased BP and reduced RBF to a lesser extent in NO-GC1-KO than
      in NO-GC2-KO. These findings indicate NO-GC1 as a target of NO to normalize RBF
      in hypertension. As these effects were not completely abolished in NO-GC1-KO and
      renal cyclic guanosine monophosphate (cGMP) levels were decreased in both NO-GC1
      KO and NO-GC2-KO, the results suggest an additional contribution of NO-GC2.
      Hence, NO-GC1 plays a predominant role in the regulation of BP and RBF,
      especially in hypertension. However, renal NO-GC2 appears to compensate the loss
      of NO-GC1, and is able to regulate renal hemodynamics under physiological
      conditions.

PMID- 29570673
TI  - Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor
      Induced Insulin Resistance and Gluconeogenesis.
AB  - Activation of the hepatic cannabinoid type 1 receptor (CB1R) induces insulin
      resistance and gluconeogenesis via endoplasmic reticulum (ER) stress, thereby
      contributing to hyperglycemia. Gomisin N (GN) is a phytochemical derived from
      Schisandra chinensis. In the current study, we investigated the inhibitory
      effects of GN on hepatic CB1R-mediated insulin resistance and gluconeogenesis in
      2-arachidonoylglycerol (AG; an agonist of CB1R)-treated HepG2 cells and in high
      fat diet (HFD)-induced obese mice. Treatment with 2-AG induced the expression of
      ER stress markers, serine/threonine phosphatase PHLPP1, Lipin1, and ceramide
      synthesis genes, but reduced the expression of ceramide degradation genes in
      HepG2 cells. However, GN reversed 2-AG-mediated effects and improved the 2-AG
      mediated impairment of insulin signaling. Furthermore, GN inhibited 2-AG-induced
      intracellular triglyceride accumulation and glucose production in HepG2 cells by
      downregulation of lipogenesis and gluconeogenesis genes, respectively. In vivo,
      GN administration to HFD obese mice reduced the HFD-induced increase in fasting
      blood glucose and insulin levels, which was accompanied with downregulation of
      HFD-induced expression of CB1R, ER stress markers, ceramide synthesis gene, and
      gluconeogenesis genes in the livers of HFD obese mice. These findings demonstrate
      that GN protects against hepatic CB1-mediated impairment of insulin signaling and
      gluconeogenesis, thereby contributing to the amelioration of hyperglycemia.

PMID- 29570674
TI  - PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in
      HaCaT Keratinocytes by cAMP.
AB  - Skin circadian clock system responds to daily changes, thereby regulating skin
      functions. Exposure of the skin to UV irradiation induces the expression of
      matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported
      both DNA repair and DNA replication are regulated by the circadian clock in mouse
      skin. However, the molecular link between circadian clock and MMP-1 has little
      been investigated. We found PERIOD protein, a morning clock component, represses
      the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy.
      Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by
      forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP
      signaling pathway. Additionally, we screened for an activator of PER that could
      repress the expression of MMP-1 using HaCaT cell line containing PER promoter
      luciferase reporter gene. Results showed Lespedeza capitate extract (LCE)
      increased PER promoter activity. LCE inhibited the expression of MMP-1 and its
      effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can
      repress the expression of MMP-1 through PER. Since circadian clock component PER
      can regulate MMP-1 expression, it might be a new molecular mechanism to develop
      therapeutics to alleviate skin aging and skin cancer.

PMID- 29570676
TI  - Supporting Beacon and Event-Driven Messages in Vehicular Platoons through Token
      Based Strategies.
AB  - Timely and reliable inter-vehicle communications is a critical requirement to
      support traffic safety applications, such as vehicle platooning. Furthermore, low
      delay communications allow the platoon to react quickly to unexpected events. In
      this scope, having a predictable and highly effective medium access control (MAC)
      method is of utmost importance. However, the currently available IEEE 802.11p
      technology is unable to adequately address these challenges. In this paper, we
      propose a MAC method especially adapted to platoons, able to transmit beacons
      within the required time constraints, but with a higher reliability level than
      IEEE 802.11p, while concurrently enabling efficient dissemination of event-driven
      messages. The protocol circulates the token within the platoon not in a round
      robin fashion, but based on beacon data age, i.e., the time that has passed since
      the previous collection of status information, thereby automatically offering
      repeated beacon transmission opportunities for increased reliability. In
      addition, we propose three different methods for supporting event-driven messages
      co-existing with beacons. Analysis and simulation results in single and multi-hop
      scenarios showed that, by providing non-competitive channel access and frequent
      retransmission opportunities, our protocol can offer beacon delivery within one
      beacon generation interval while fulfilling the requirements on low-delay
      dissemination of event-driven messages for traffic safety applications.

PMID- 29570675
TI  - An Arabidopsis Clathrin Assembly Protein with a Predicted Role in Plant Defense
      Can Function as an Adenylate Cyclase.
AB  - Adenylate cyclases (ACs), much like guanylate cyclases (GCs), are increasingly
      recognized as essential parts of many plant processes including biotic and
      abiotic stress responses. In order to identify novel ACs, we have applied a
      search motif derived from experimentally tested GCs and identified a number of
      Arabidopsis thaliana candidates including a clathrin assembly protein (AT1G68110;
      AtClAP). AtClAP contains a catalytic centre that can complement the AC-deficient
      mutant cyaA in E. coli, and a recombinant AtClAP fragment (AtClAP261-379) can
      produce cyclic adenosine 3',5' monophosphate (cAMP) from adenosine triphosphate
      (ATP) in vitro. Furthermore, an integrated analysis of gene expression and
      expression correlation implicate cAMP in pathogen defense and in actin
      cytoskeletal remodeling during endocytic internalization.

PMID- 29570677
TI  - Gas Sensing Properties of p-Co3O4/n-TiO2 Nanotube Heterostructures.
AB  - In this paper, we fabricated p-Co3O4/n-TiO2 heterostructures and investigated
      their gas sensing properties. The structural and morphological characterization
      were performed by scanning electron microscopy (SEM), X-ray diffraction (XRD),
      and X-ray photoelectron spectroscopy analysis (XPS). The electrical properties of
      the heterostructure were studied within the temperature range from 293 K to 423
      K. Changes in electrical properties and sensing behavior against reducing and
      oxidizing gases were attributed to the formation of p-n heterojunctions at the
      Co3O4 and TiO2 interface. In comparison with sensing performed with pristine TiO2
      nanotubes (NTs), a significant improvement in H2 sensing at 200  degrees C was
      observed, while the sensing response against NO2 decreased for the
      heterostructures. Additionally, a response against toluene gas, in contrast to
      pristine TiO2 NTs, appeared in the Co3O4/TiO2 heterostructure samples.

PMID- 29570678
TI  - Convolutional Neural Network-Based Classification of Driver's Emotion during
      Aggressive and Smooth Driving Using Multi-Modal Camera Sensors.
AB  - Because aggressive driving often causes large-scale loss of life and property,
      techniques for advance detection of adverse driver emotional states have become
      important for the prevention of aggressive driving behaviors. Previous studies
      have primarily focused on systems for detecting aggressive driver emotion via
      smart-phone accelerometers and gyro-sensors, or they focused on methods of
      detecting physiological signals using electroencephalography (EEG) or
      electrocardiogram (ECG) sensors. Because EEG and ECG sensors cause discomfort to
      drivers and can be detached from the driver's body, it becomes difficult to focus
      on bio-signals to determine their emotional state. Gyro-sensors and
      accelerometers depend on the performance of GPS receivers and cannot be used in
      areas where GPS signals are blocked. Moreover, if driving on a mountain road with
      many quick turns, a driver's emotional state can easily be misrecognized as that
      of an aggressive driver. To resolve these problems, we propose a convolutional
      neural network (CNN)-based method of detecting emotion to identify aggressive
      driving using input images of the driver's face, obtained using near-infrared
      (NIR) light and thermal camera sensors. In this research, we conducted an
      experiment using our own database, which provides a high classification accuracy
      for detecting driver emotion leading to either aggressive or smooth (i.e.,
      relaxed) driving. Our proposed method demonstrates better performance than
      existing methods.

PMID- 29570679
TI  - Electrochemical Aptasensors for Food and Environmental Safeguarding: A Review.
AB  - Food and environmental monitoring is one of the most important aspects of dealing
      with recent threats to human well-being and ecosystems. In this framework,
      electrochemical aptamer-based sensors are resilient due to their ability to
      resolve food and environmental contamination. An aptamer-based sensor is a
      compact analytical device combining an aptamer as the bio-sensing element
      integrated on the transducer surface. Aptamers display many advantages as
      biorecognition elements in sensor development when compared to affinity-based
      (antibodies) sensors. Aptasensors are small, chemically unchanging, and
      inexpensive. Moreover, they offer extraordinary elasticity and expediency in the
      design of their assemblies, which has led to innovative sensors that show
      tremendous sensitivity and selectivity. This review will emphasize recent food
      and environmental safeguarding using aptasensors; there are good prospects for
      their performance as a supplement to classical techniques.

PMID- 29570680
TI  - A Highly Thermostable In2O3/ITO Thin Film Thermocouple Prepared via Screen
      Printing for High Temperature Measurements.
AB  - An In2O3/ITO thin film thermocouple was prepared via screen printing. Glass
      additives were added to improve the sintering process and to increase the density
      of the In2O3/ITO films. The surface and cross-sectional images indicate that both
      the grain size and densification of the ITO and In2O3 films increased with the
      increase in annealing time. The thermoelectric voltage of the In2O3/ITO
      thermocouple was 53.5 mV at 1270  degrees C at the hot junction. The average
      Seebeck coefficient of the thermocouple was calculated as 44.5 MUV/ degrees C.
      The drift rate of the In2O3/ITO thermocouple was 5.44  degrees C/h at a measuring
      time of 10 h at 1270  degrees C.

PMID- 29570682
TI  - Resistance to 6-Methylpurine is Conferred by Defective Adenine
      Phosphoribosyltransferase in Tetrahymena.
AB  - 6-methylpurine (6mp) is a toxic analog of adenine that inhibits RNA and protein
      synthesis and interferes with adenine salvage mediated by adenine
      phosphoribosyltransferase (APRTase). Mutants of the ciliated protist Tetrahymena
      thermophila that are resistant to 6mp were isolated in 1974, but the mechanism of
      resistance has remained unknown. To investigate 6mp resistance in T. thermophila,
      we created 6mp-resistant strains and identified a mutation in the APRTase genomic
      locus (APRT1) that is responsible for 6mp resistance. While overexpression of the
      mutated APRT1 allele in 6mp-sensitive cells did not confer resistance to 6mp,
      reduced wild-type APRT1 expression resulted in a significant decrease in
      sensitivity to 6mp. Knocking out or reducing the expression of APRT1 by RNA
      interference (RNAi) did not affect robust cell growth, which indicates that
      adenine salvage is redundant or that de novo synthesis pathways provide
      sufficient adenosine monophosphate for viability. We also explored whether 6mp
      resistance could be used as a novel inducible selection marker by generating 6mp-
      and paromomycin-resistant double mutants. While 6mp- and paromomycin-resistant
      double mutants did express fluorescent proteins in an RNAi-based system, the
      system requires optimization before 6mp resistance can be used as an effective
      inducible selection marker.

PMID- 29570683
TI  - Extraction of Antioxidant Phenolic Compounds from Brewer's Spent Grain:
      Optimization and Kinetics Modeling.
AB  - The kinetics of polyphenol extraction from brewer's spent grain (BSG), using a
      batch system, ultrasound assistance, and microwave assistance and the evolution
      of antioxidant capacity of these extracts over time, were studied. The main
      parameters of extraction employed in the batch system were evaluated, and, by
      applying response surface analysis, the following optimal conditions were
      obtained: Liquid/solid ratio of 30:1 mL/g at 80  degrees C, using 72% (v/v)
      ethanol:water as the solvent system. Under these optimized conditions, ultrasound
      assistance demonstrated the highest extraction rate and equilibrium yield, as
      well as shortest extraction times, followed by microwave assistance. Among the
      mathematical models used, Patricelli's model proved the most suitable for
      describing the extraction kinetics for each method tested, and is therefore able
      to predict the response values and estimate the extraction rates and potential
      maximum yields in each case.

PMID- 29570684
TI  - Sensor-Based Optimization Model for Air Quality Improvement in Home IoT.
AB  - We introduce current home Internet of Things (IoT) technology and present
      research on its various forms and applications in real life. In addition, we
      describe IoT marketing strategies as well as specific modeling techniques for
      improving air quality, a key home IoT service. To this end, we summarize the
      latest research on sensor-based home IoT, studies on indoor air quality, and
      technical studies on random data generation. In addition, we develop an air
      quality improvement model that can be readily applied to the market by acquiring
      initial analytical data and building infrastructures using spectrum/density
      analysis and the natural cubic spline method. Accordingly, we generate related
      data based on user behavioral values. We integrate the logic into the existing
      home IoT system to enable users to easily access the system through the Web or
      mobile applications. We expect that the present introduction of a practical
      marketing application method will contribute to enhancing the expansion of the
      home IoT market.

PMID- 29570685
TI  - Synthesis, Characterization, and Antifungal Activity of Novel
      Benzo[4,5]imidazo[1,2-d][1,2,4]triazine Derivatives.
AB  - A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2
      d][1,2,4]triazine 4a-4w were designed and conveniently synthesized via the
      intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1
      (substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a-3g. The structures
      of all target compounds were characterized by FT-IR, 1H NMR, 13C NMR, and EI-MS,
      of which, the structure of compound 4n was further determined by the single
      crystal X-ray diffraction. The crystal structure of 4n was crystallized in the
      triclinic crystal system, space group P 1 - with a = 9.033 (6) A, b = 10.136 (7)
      A, c = 10.396 (7) A, alpha = 118.323 (7) degrees , beta = 91.750 (8) degrees ,
      gamma = 104.198 (7) degrees , Z = 2, V = 800.2 (9) A3; total R indices: R1 =
      0.0475, wR2 = 0.1284. The antifungal activity of title compounds 4a-4w in vitro
      against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia
      solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the
      bioassay results demonstrated that most of the title compounds exhibited obvious
      fungicidal activities at 50 MUg/mL. This work indicated that
      benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new
      leading structure in searching for novel agricultural fungicides.

PMID- 29570686
TI  - Design, Synthesis, and Biological Evaluation of Axitinib Derivatives.
AB  - Axitinib is an approved kinase inhibitor for the therapy of advanced metastatic
      renal cell carcinoma (RCC). It prevents angiogenesis, cellular adhesion, and
      induces apoptosis of cancer cells. Here, nine axitinib derivatives were designed
      by replacing the C=C moiety with the N=N group, and the substituted benzene or
      pyrrole analogs were considered to replace the pyridine ring. Biological activity
      results showed that most of nascent derivatives exhibited favorable VEGFR-2
      kinase inhibitory activities, and TM6, 7, 9, and 11 behaved more potent anti
      proliferative activities than axitinib. This novel series of compounds shows a
      potential for the treatment of solid tumors and other diseases where angiogenesis
      plays an important role.

PMID- 29570687
TI  - Scaling-Up the Impact of Aflatoxin Research in Africa. The Role of Social
      Sciences.
AB  - At the interface between agriculture and nutrition, the aflatoxin contamination
      of food and feed touches on agriculture, health, and trade. For more than three
      decades now, the problem of aflatoxin has been researched in Africa. The interest
      of development cooperation for aflatoxin and the support to aflatoxin mitigation
      projects has its ups and downs. The academic world and the development world
      still seem to operate in different spheres and a collaboration is still
      challenging due to the complexity of the contamination sources at pre-harvest and
      post-harvest levels. There is a growing call by research funders and development
      actors for the impact of solutions at a scale. The solutions to mitigate
      aflatoxin contamination require new ways of working together. A more prominent
      role is to be played by social scientists. The role of social scientists in
      scaling-up the impact of aflatoxin research in Africa and the proposed mitigation
      solutions is to ensure that awareness, advantage, affordability, and access are
      systematically assessed. Aflatoxin-reduced staple foods and feed would be an
      agricultural result with a considerable health and food safety impact.

PMID- 29570681
TI  - Wnt Signalling in Gastrointestinal Epithelial Stem Cells.
AB  - Wnt signalling regulates several cellular functions including proliferation,
      differentiation, apoptosis and migration, and is critical for embryonic
      development. Stem cells are defined by their ability for self-renewal and the
      ability to be able to give rise to differentiated progeny. Consequently, they are
      essential for the homeostasis of many organs including the gastrointestinal
      tract. This review will describe the huge advances in our understanding of how
      stem cell functions in the gastrointestinal tract are regulated by Wnt
      signalling, including how deregulated Wnt signalling can hijack these functions
      to transform cells and lead to cancer.

PMID- 29570690
TI  - Convolutional Neural Network-Based Shadow Detection in Images Using Visible Light
      Camera Sensor.
AB  - Recent developments in intelligence surveillance camera systems have enabled more
      research on the detection, tracking, and recognition of humans. Such systems
      typically use visible light cameras and images, in which shadows make it
      difficult to detect and recognize the exact human area. Near-infrared (NIR) light
      cameras and thermal cameras are used to mitigate this problem. However, such
      instruments require a separate NIR illuminator, or are prohibitively expensive.
      Existing research on shadow detection in images captured by visible light cameras
      have utilized object and shadow color features for detection. Unfortunately,
      various environmental factors such as illumination change and brightness of
      background cause detection to be a difficult task. To overcome this problem, we
      propose a convolutional neural network-based shadow detection method.
      Experimental results with a database built from various outdoor surveillance
      camera environments, and from the context-aware vision using image-based active
      recognition (CAVIAR) open database, show that our method outperforms previous
      works.

PMID- 29570689
TI  - Association between Maternal and Foetal Erythrocyte Fatty Acid Profiles and Birth
      Weight.
AB  - Regular foetal development is crucial for assuring good health status in the
      offspring. The quality and quantity of maternal dietary fatty acids (FAs) can
      affect growth. The study aimed to: (1) investigate the association of
      maternal/foetal lipid profiles with birth weight (BW); and (2) compare these
      profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA)
      infants. FAs were measured in erythrocyte membranes using gas chromatography
      analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile
      regression, a significant association between BW and levels of maternal linoleic
      acid (LA; C18:2, n-6; coefficient: 18.66; p = 0.010), arachidonic acid (AA;
      C20:4, n-6; coefficient: 11.35; p = 0.007), docosahexaenoic acid (DHA; C22:6, n
      3; coefficient: 29.73; p = 0.007), polyunsaturated FAs (coefficient: 8.55; p =
      0.001), foetal DHA (coefficient: -22.82; p = 0.037), and saturated FAs
      (coefficient: -65.41; p = 0.002) was found. Myristic (C14:0) and pentadecanoic
      acids (C15:0), both maternal (p = 0.000; p = 0.017) and foetal (p = 0.009; p =
      0.002), and maternal erucic acid (C22:1, n-9; p = 0.026) were found at higher
      levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and
      omega 6 FAs levels were higher in AGA infants (p = 0.037; p = 0.003; p = 0.026,
      respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are
      positively related to BW, while a lipid profile rich in saturated FAs and erucic
      acid may influence the risk of SGA.

PMID- 29570691
TI  - A Multi-Hop Clustering Mechanism for Scalable IoT Networks.
AB  - It is expected that up to 26 billion Internet of Things (IoT) equipped with
      sensors and wireless communication capabilities will be connected to the Internet
      by 2020 for various purposes. With a large scale IoT network, having each node
      connected to the Internet with an individual connection may face serious
      scalability issues. The scalability problem of the IoT network may be alleviated
      by grouping the nodes of the IoT network into clusters and having a
      representative node in each cluster connect to the Internet on behalf of the
      other nodes in the cluster instead of having a per-node Internet connection and
      communication. In this paper, we propose a multi-hop clustering mechanism for IoT
      networks to minimize the number of required Internet connections. Specifically,
      the objective of proposed mechanism is to select the minimum number of
      coordinators, which take the role of a representative node for the cluster, i.e.,
      having the Internet connection on behalf of the rest of the nodes in the cluster
      and to map a partition of the IoT nodes onto the selected set of coordinators to
      minimize the total distance between the nodes and their respective coordinator
      under a certain constraint in terms of maximum hop count between the IoT nodes
      and their respective coordinator. Since this problem can be mapped into a set
      cover problem which is known as NP-hard, we pursue a heuristic approach to solve
      the problem and analyze the complexity of the proposed solution. Through a set of
      experiments with varying parameters, the proposed scheme shows 63-87.3% reduction
      of the Internet connections depending on the number of the IoT nodes while that
      of the optimal solution is 65.6-89.9% in a small scale network. Moreover, it is
      shown that the performance characteristics of the proposed mechanism coincide
      with expected performance characteristics of the optimal solution in a large
      scale network.

PMID- 29570688
TI  - Diagnosis, Evaluation and Treatment of Pulmonary Arterial Hypertension in
      Children.
AB  - Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary
      arteries, is associated with significant morbidity and mortality for affected
      children. PH is associated with a wide variety of potential underlying causes,
      including cardiac, pulmonary, hematologic and rheumatologic abnormalities.
      Regardless of the cause, for many patients the natural history of PH involves
      progressive elevation in pulmonary arterial resistance and pressure, right
      ventricular dysfunction, and eventually heart failure. In recent years, a number
      of pulmonary arterial hypertension (PAH)-targeted therapies have become available
      to reduce pulmonary artery pressure and improve outcome. A growing body of
      evidence in both the adult and pediatric literature demonstrates enhanced quality
      of life, functional status, and survival among treated patients. This review
      provides a description of select etiologies of PH seen in pediatrics and an
      update on the most recent data pertaining to evaluation and management of
      children with PH/PAH. The available evidence for specific classes of PAH-targeted
      therapies in pediatrics is additionally discussed.

PMID- 29570692
TI  - Preclinical Evaluation of Vemurafenib as Therapy for BRAFV600E Mutated Sarcomas.
AB  - : The BRAFV600E mutation, which in melanoma is targetable with vemurafenib, is
      also found in sarcomas and we here evaluate the therapeutic potential in sarcoma
      cell lines. METHODS: Four sarcoma cell lines harboring the BRAFV600E mutation,
      representing liposarcomas (SA-4 and SW872), Ewing sarcoma (A673) and atypical
      synovial sarcoma (SW982), were treated with vemurafenib and the effects on cell
      growth, apoptosis, cell cycle progression and cell signaling were determined.
      RESULTS: Vemurafenib induced a strong cytostatic effect in SA-4 cells, mainly due
      to cell cycle arrest, whereas only moderate levels of apoptosis were observed.
      However, a high dose was required compared to BRAFV600E mutated melanoma cells,
      and removal of vemurafenib demonstrated that the continuous presence of drug was
      required for sustained growth inhibition. A limited growth inhibition was
      observed in the other three cell lines. Protein analyses demonstrated reduced
      phosphorylation of ERK during treatment with vemurafenib in all the four sarcoma
      cell lines confirming that the MAPK pathway is active in these cell lines, and
      that the pathway can be inhibited by vemurafenib, but also that these cells can
      proliferate despite this. CONCLUSIONS: These findings indicate that vemurafenib
      alone would not be an efficient therapy against BRAFV600E mutated sarcomas.
      However, further investigations of combination with other drugs are warranted.

PMID- 29570693
TI  - Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New
      Therapeutic Strategy in Parkinson's Disease.
AB  - This concept article aims to show the rationale of targeting extracellular alpha
      Synuclein (alpha-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove
      this protein from the brain in Parkinson's disease (PD). Misfolding and
      intracellular aggregation of alpha-synuclein into Lewy bodies are thought to be
      crucial in the pathogenesis of PD. Recent research has shown that small amounts
      of monomeric and oligomeric alpha-synuclein are released from neuronal cells by
      exocytosis and that this extracellular alpha-synuclein contributes to
      neurodegeneration, progressive spreading of alpha-synuclein pathology, and
      neuroinflammation. In PD, extracellular oligomeric-alpha-synuclein moves in
      constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we
      expect that continuous depletion of oligomeric-alpha-synuclein in the CSF will
      produce a steady clearance of the protein in the ISF, preventing transmission and
      deposition in the brain.

PMID- 29570695
TI  - Lack of Substantial Post-Cessation Weight Increase in Electronic Cigarettes
      Users.
AB  - Minimization of post-cessation weight gain in quitters is important, but existing
      approaches (e.g., antismoking medications) shows only limited success. We
      investigated changes in body weight in smokers who quit or reduced substantially
      their cigarette consumption by switching to electronic cigarettes (ECs) use. Body
      weight and smoking/vaping history were extracted from medical records of smokers
      and ex-smokers to match three study groups: (1) regular EC users on at least two
      consecutive follow-up visits; (2) regular smokers (and not using ECs); (3)
      subjects who reported sustained smoking abstinence after completing a cessation
      program. Review of their medical records was conducted at two follow-up visits at
      6- (F/U 6m) and 12-months (F/U 12m). A total of 86 EC users, 93 regular smokers,
      and 44 quitters were studied. In the EC users study group, cigarettes/day use
      decreased from 21.1 at baseline to 1.8 at F/U 12m (p < 0.0001). Dual usage was
      reported by approximately 50% of EC users. Both within factor (time, p < 0.0001)
      and between factor (study groups, p < 0.0001) produced significant effect on
      weight (% change from baseline), with a significant 4.8% weight gain from
      baseline in the quitters study group at F/U 12m. For the EC users, weight gain at
      F/U 12m was only 1.5% of baseline. There was no evidence of post-cessation weight
      increase in those who reduced substantially cigarette consumption by switching to
      ECs (i.e., dual users) and only modest post-cessation weight increase was
      reported in exclusive EC users at F/U 12m. By reducing weight gain and tobacco
      consumption, EC-based interventions may promote an overall improvement in quality
      of life.

PMID- 29570696
TI  - Patternable Poly(chloro-p-xylylene) Film with Tunable Surface Wettability
      Prepared by Temperature and Humidity Treatment on a Polydimethylsiloxane/Silica
      Coating.
AB  - Poly(chloro-p-xylylene) (PPXC) film has a water contact angle (WCA) of only about
      84 degrees . It is necessary to improve its hydrophobicity to prevent liquid
      water droplets from corroding or electrically shorting metallic circuits of
      semiconductor devices, sensors, microelectronics, and so on. Herein, we reported
      a facile approach to improve its surface hydrophobicity by varying surface
      pattern structures under different temperature and relative humidity (RH)
      conditions on a thermal curable polydimethylsiloxane (PDMS) and hydrophobic
      silica (SiO2) nanoparticle coating. Three distinct large-scale surface patterns
      were obtained mainly depending on the contents of SiO2 nanoparticles. The
      regularity of patterns was mainly controlled by the temperature and RH
      conditions. By changing the pattern structures, the surface wettability of PPXC
      film could be improved and its WCA was increased from 84 degrees  to 168 degrees
      , displaying a superhydrophobic state. Meanwhile, it could be observed that water
      droplets on PPXC film with superhydrophobicity were transited from a "Wenzel"
      state to a "Cassie" state. The PPXC film with different surface patterns of 200
      MUm * 200 MUm and the improved surface hydrophobicity showed wide application
      potentials in self-cleaning, electronic engineering, micro-contact printing, cell
      biology, and tissue engineering.

PMID- 29570698
TI  - Sensor Fusion to Estimate the Depth and Width of the Weld Bead in Real Time in
      GMAW Processes.
AB  - The arc welding process is widely used in industry but its automatic control is
      limited by the difficulty in measuring the weld bead geometry and closing the
      control loop on the arc, which has adverse environmental conditions. To address
      this problem, this work proposes a system to capture the welding variables and
      send stimuli to the Gas Metal Arc Welding (GMAW) conventional process with a
      constant voltage power source, which allows weld bead geometry estimation with an
      open-loop control. Dynamic models of depth and width estimators of the weld bead
      are implemented based on the fusion of thermographic data, welding current and
      welding voltage in a multilayer perceptron neural network. The estimators were
      trained and validated off-line with data from a novel algorithm developed to
      extract the features of the infrared image, a laser profilometer was implemented
      to measure the bead dimensions and an image processing algorithm that measures
      depth by making a longitudinal cut in the weld bead. These estimators are
      optimized for embedded devices and real-time processing and were implemented on a
      Field-Programmable Gate Array (FPGA) device. Experiments to collect data, train
      and validate the estimators are presented and discussed. The results show that
      the proposed method is useful in industrial and research environments.

PMID- 29570697
TI  - DNA Damage, Mutagenesis and Cancer.
AB  - A large number of chemicals and several physical agents, such as UV light and
      gamma-radiation, have been associated with the etiology of human cancer.
      Generation of DNA damage (also known as DNA adducts or lesions) induced by these
      agents is an important first step in the process of carcinogenesis. Evolutionary
      processes gave rise to DNA repair tools that are efficient in repairing damaged
      DNA; yet replication of damaged DNA may take place prior to repair, particularly
      when they are induced at a high frequency. Damaged DNA replication may lead to
      gene mutations, which in turn may give rise to altered proteins. Mutations in an
      oncogene, a tumor-suppressor gene, or a gene that controls the cell cycle can
      generate a clonal cell population with a distinct advantage in proliferation.
      Many such events, broadly divided into the stages of initiation, promotion, and
      progression, which may occur over a long period of time and transpire in the
      context of chronic exposure to carcinogens, can lead to the induction of human
      cancer. This is exemplified in the long-term use of tobacco being responsible for
      an increased risk of lung cancer. This mini-review attempts to summarize this
      wide area that centers on DNA damage as it relates to the development of human
      cancer.

PMID- 29570694
TI  - Enteric Virome Sensing-Its Role in Intestinal Homeostasis and Immunity.
AB  - Pattern recognition receptors (PRRs) sensing commensal microorganisms in the
      intestine induce tightly controlled tonic signaling in the intestinal mucosa,
      which is required to maintain intestinal barrier integrity and immune
      homeostasis. At the same time, PRR signaling pathways rapidly trigger the innate
      immune defense against invasive pathogens in the intestine. Intestinal epithelial
      cells and mononuclear phagocytes in the intestine and the gut-associated lymphoid
      tissues are critically involved in sensing components of the microbiome and
      regulating immune responses in the intestine to sustain immune tolerance against
      harmless antigens and to prevent inflammation. These processes have been mostly
      investigated in the context of the bacterial components of the microbiome so far.
      The impact of viruses residing in the intestine and the virus sensors, which are
      activated by these enteric viruses, on intestinal homeostasis and inflammation is
      just beginning to be unraveled. In this review, we will summarize recent findings
      indicating an important role of the enteric virome for intestinal homeostasis as
      well as pathology when the immune system fails to control the enteric virome. We
      will provide an overview of the virus sensors and signaling pathways, operative
      in the intestine and the mononuclear phagocyte subsets, which can sense viruses
      and shape the intestinal immune response. We will discuss how these might
      interact with resident enteric viruses directly or in context with the bacterial
      microbiome to affect intestinal homeostasis.

PMID- 29570699
TI  - MicroRNA-194 Regulates the Development and Differentiation of Sensory Patches and
      Statoacoustic Ganglion of Inner Ear by Fgf4.
AB  - BACKGROUND MicroRNA 194 is involved in the differentiation of various types of
      cells, such as adipose derived stem cells, human embryonic stem cells, and bone
      marrow mesenchymal stem cells. Previously, we found that miR-194 was highly
      expressed in the inner ear sensory patch and neurons in mice embryos. However,
      the role of miR-194 in the development of the inner ear and its underlying
      mechanism have not been elucidated yet. MATERIAL AND METHODS The expression level
      of miR-194 has been altered by using antisense morpholino oligonucleotides (MO)
      and synthesized miRNAs in zebrafish. RESULTS We found that miR-194 was vastly
      expressed in the inner ear and central nervous system (CNS) in zebrafish. Loss of
      function of miR-194 could strongly affected the development of zebrafish embryos,
      including delayed embryonic development, edema of the pericardium, small head,
      axial deviation, delayed development of inner ear, closer location of two
      otoliths, delayed fusion of the semicircular canals, and abnormal otolith number
      in some cases. In addition, the behavior of zebrafish was also adversely affected
      with impaired balance and biased swimming route. Misexpression of miR-194 could
      strongly affected the development and differentiation of spiral ganglion neuron
      (SGN) in inner ear through Fgf4 in vitro. Similar results have also been observed
      that the overexpression and knockdown of miR-194 strongly disturbed the
      development and differentiation of the sensory patches and Statoacoustic ganglion
      (SAG) through Fgf4 in zebrafish in vivo. Our results indicated that miR-194 may
      regulate the development and differentiation of sensory patches and SAG through
      Fgf4. CONCLUSIONS Our data revealed a vital role of miR-194 in regulating the
      development and differentiation of the inner ear.

PMID- 29570700
TI  - Fluctuating Finite Element Analysis (FFEA): A continuum mechanics software tool
      for mesoscale simulation of biomolecules.
AB  - Fluctuating Finite Element Analysis (FFEA) is a software package designed to
      perform continuum mechanics simulations of proteins and other globular
      macromolecules. It combines conventional finite element methods with stochastic
      thermal noise, and is appropriate for simulations of large proteins and protein
      complexes at the mesoscale (length-scales in the range of 5 nm to 1 MUm), where
      there is currently a paucity of modelling tools. It requires 3D volumetric
      information as input, which can be low resolution structural information such as
      cryo-electron tomography (cryo-ET) maps or much higher resolution atomistic co
      ordinates from which volumetric information can be extracted. In this article we
      introduce our open source software package for performing FFEA simulations which
      we have released under a GPLv3 license. The software package includes a C ++
      implementation of FFEA, together with tools to assist the user to set up the
      system from Electron Microscopy Data Bank (EMDB) or Protein Data Bank (PDB) data
      files. We also provide a PyMOL plugin to perform basic visualisation and
      additional Python tools for the analysis of FFEA simulation trajectories. This
      manuscript provides a basic background to the FFEA method, describing the
      implementation of the core mechanical model and how intermolecular interactions
      and the solvent environment are included within this framework. We provide
      prospective FFEA users with a practical overview of how to set up an FFEA
      simulation with reference to our publicly available online tutorials and manuals
      that accompany this first release of the package.

PMID- 29570701
TI  - Infant outcome at four years of age after intrapartum sampling of scalp blood
      lactate for fetal assessment. A cohort study.
AB  - OBJECTIVE: To correlate the value of lactate in fetal scalp blood at delivery and
      the outcomes of the offspring at four years of age. METHODS: Cases where scalp
      blood lactate was taken within sixty minutes before delivery were identified from
      the randomized trial "Determination of pH or lactate in fetal scalp blood in
      management of intrapartum fetal distress". Data were grouped according to the
      generally accepted cutoffs for normality, pre-acidemia, acidemia and
      concentrations above mean +2 SD during the second stage. The outcome measures
      included gross-/fine motor function, vision, hearing, speaking and cognitive
      disorders, signs of central motor damage and referral to specialized pediatric
      services. RESULTS: 307 cases were available for final analyse. With normal scalp
      lactate concentration, the number of children with a diagnosed disorder was lower
      compared to the pre-acidemic/acidemic groups, although the findings were only
      significant for fine motor dysfunction (p = 0.036). Elevated lactate values were
      significantly associated with increased risk for a poorer capacity of attention
      and understanding of instructions (OR 1.37, 95% CI 1.07-1.74), and for fine motor
      dysfunction (OR 1.22, 95% CI 1.00-1.49) at the age of four. CONCLUSION: Higher
      levels of lactate in fetal scalp blood seems to be associated with increased risk
      of an aberrant developmental outcome at four years of age in some areas.

PMID- 29570702
TI  - Sustainable food security in India-Domestic production and macronutrient
      availability.
AB  - India has been perceived as a development enigma: Recent rates of economic growth
      have not been matched by similar rates in health and nutritional improvements. To
      meet the second Sustainable Development Goal (SDG2) of achieving zero hunger by
      2030, India faces a substantial challenge in meeting basic nutritional needs in
      addition to addressing population, environmental and dietary pressures. Here we
      have mapped-for the first time-the Indian food system from crop production to
      household-level availability across three key macronutrients categories of
      'calories', 'digestible protein' and 'fat'. To better understand the potential of
      reduced food chain losses and improved crop yields to close future food deficits,
      scenario analysis was conducted to 2030 and 2050. Under India's current self
      sufficiency model, our analysis indicates severe shortfalls in availability of
      all macronutrients across a large proportion (>60%) of the Indian population. The
      extent of projected shortfalls continues to grow such that, even in ambitious
      waste reduction and yield scenarios, enhanced domestic production alone will be
      inadequate in closing the nutrition supply gap. We suggest that to meet SDG2
      India will need to take a combined approach of optimising domestic production and
      increasing its participation in global trade.

PMID- 29570703
TI  - Injectable silicone rubber for ocular implantation after evisceration.
AB  - OBJECTIVE: To investigate the usefulness of addition type liquid silicone rubber
      (ATLSR) as injectable implant after evisceration to maintain the eyeball volume
      in an animal experiment. METHODS: Twelve adult New Zealand white rabbits were
      included. One eye of each rabbit was randomly selected for evisceration with the
      fellow eye as control. ATLSR was injected to fill the eyeball socket after
      evisceration. In vivo observation and photographs were performed up to 24 weeks
      post-op. Two rabbits were sacrificed respectively at post-operative week 1, 2, 4,
      8, 12 and 24. After enucleation, the vertical, horizontal and sagittal diameters
      of the experimental eyeballs were measured and compared with the control eyes.
      Histopathological studies were performed to evaluate signs of inflammation.
      RESULTS: Cornea remained clear throughout the observation period despite mild
      epithelial edema and neovascularization. Compared to the control eyes, the
      experimental eyes were significantly smaller in vertical diameter (17.00+/-1.17
      vs. 17.54+/-1.11 mm, P<0.001), but larger in sagittal diameter (16.85+/-1.48 vs.
      16.40+/-1.38 mm, P = 0.008), and had no significant difference in horizontal
      diameter (17.49+/-1.53 vs. 17.64+/-1.21 mm, P = 0.34). Postoperative inflammation
      was observed at one week after surgery, which peaked at 2-3 weeks, then regressed
      gradually. At week 12 and week 24, most of the inflammatory cells disappeared
      with some residual plasma cells and eosinophils. CONCLUSION: Injectable addition
      type silicon rubber may be a good choice for ocular implantation after
      evisceration, maintaining eyeball volume and cosmetically satisfactory when
      compared to the fellow eye. Spontaneous regression of inflammation implied good
      biocompatibility for at least 24 weeks.

PMID- 29570704
TI  - The TIE1 transcriptional repressor controls shoot branching by directly
      repressing BRANCHED1 in Arabidopsis.
AB  - Shoot branching is a major determinant of plant architecture and is regulated by
      both endogenous and environmental factors. BRANCHED1 (BRC1) is a central local
      regulator that integrates signals controlling shoot branching. So far, the
      regulation of BRC1 activity at the protein level is still largely unknown. In
      this study, we demonstrated that TIE1 (TCP interactor containing EAR motif
      protein 1), a repressor previously identified as an important factor in the
      control of leaf development, also regulates shoot branching by repressing BRC1
      activity. TIE1 is predominantly expressed in young axillary buds. The gain-of
      function mutant tie1-D produced more branches and the overexpression of TIE1
      recapitulated the increased branching of tie1-D, while disruption of TIE1
      resulted in lower bud activity and fewer branches. We also demonstrated that the
      TIE1 protein interacts with BRC1 in vitro and in vivo. Expression of BRC1 fused
      with the C-terminus of the TIE1 protein in wild type caused excessive branching
      similar to that observed in tie1-D and brc1 loss-of-function mutants.
      Transcriptome analyses revealed that TIE1 regulated about 30% of the BRC1
      dependent genes, including the BRC1 direct targets HB21, HB40 and HB53. These
      results indicate that TIE1 acts as a positive regulator of shoot branching by
      directly repressing BRC1 activity. Thus, our results reveal that TIE1 is an
      important shoot branching regulator, and provide new insights in the post
      transcriptional regulation of the TCP transcription factor BRC1.

PMID- 29570705
TI  - Random support vector machine cluster analysis of resting-state fMRI in
      Alzheimer's disease.
AB  - Early diagnosis is critical for individuals with Alzheimer's disease (AD) in
      clinical practice because its progress is irreversible. In the existing
      literature, support vector machine (SVM) has always been applied to distinguish
      between AD and healthy controls (HC) based on neuroimaging data. But previous
      studies have only used a single SVM to classify AD and HC, and the accuracy is
      not very high and generally less than 90%. The method of random support vector
      machine cluster was proposed to classify AD and HC in this paper. From the
      Alzheimer's Disease Neuroimaging Initiative database, the subjects including 25
      AD individuals and 35 HC individuals were obtained. The classification accuracy
      could reach to 94.44% in the results. Furthermore, the method could also be used
      for feature selection and the accuracy could be maintained at the level of
      94.44%. In addition, we could also find out abnormal brain regions (inferior
      frontal gyrus, superior frontal gyrus, precentral gyrus and cingulate cortex). It
      is worth noting that the proposed random support vector machine cluster could be
      a new insight to help the diagnosis of AD.

PMID- 29570706
TI  - Intra-operative biopsy in chronic sinusitis detects pathogenic Escherichia coli
      that carry fimG/H, fyuA and agn43 genes coding biofilm formation.
AB  - The aim of this study was to investigate whether or not surgical biopsy of sinus
      tissue in chronic sinusitis, not responsive to treatment, would detect E. coli.
      We intended to evaluate E. coli virulence genes, therefore dispute the causal
      role of such an unusual microorganism in chronic sinusitis, as well as consider
      effective pathogen-targeted therapy. Patients with E. coli isolated by intra
      operative puncture biopsy were included in the study. Genetic analysis of E. coli
      isolates, including phylogenetic grouping and virulence factor characteristics,
      were done by multiplex PCR. We identified 26 patients with chronic sinusitis, in
      which 26 E. coli isolates were cultured. The E. coli isolates belonged mainly to
      pathogenic phylogenetic group B2, and carried multiple virulence genes. Three
      genes in particular were present in all (100%) of examined isolates, they were
      (1) marker agn43 gene for forming biofilm, (2) type 1 fimbriae (fimG/H gene) and
      (3) yersiniabactin receptor (fyuA). Furthermore, a pseudo-phylogenetic tree of
      virulence genes distribution revealed possible cooperation between agn43, fimG/H,
      and fyuA in the coding of biofilm formation. Intra-operative-biopsy and culture
      based therapy, targeting the isolated E. coli, coincided with long-term
      resolution of symptoms. This is the first report demonstrating an association
      between a highly pathogenic E. coli, chronic sinus infection, and resolution of
      symptoms upon E. coli targeted therapy, a significant finding due to the fact
      that E. coli has not been considered to be a commensal organism of the oropharynx
      or sinuses. We postulate that the simultaneous presence of three genes, each
      coding biofilm formation, may in part account for the chronicity of E. coli
      sinusitis.

PMID- 29570708
TI  - Dermatological guidelines for monitoring methotrexate treatment reduce drug
      survival compared to rheumatological guidelines.
AB  - BACKGROUND: Methotrexate (MTX) is widely used as disease modifying treatment for
      psoriasis and psoriatic arthritis (PsA). Rheumatological and dermatological
      guidelines to prevent MTX-induced adverse events diverge in the number and
      frequency of blood tests. These differences are not based on evidence indicating
      a higher risk for patients with psoriasis compared to PsA or rheumatic arthritis
      (RA). This raises the question if multiple testing increases safety, or results
      in false positive signals potentially leading to early withdrawal of an effective
      treatment. OBJECTIVE: Compare the effects of MTX monitoring strategies by
      rheumatologists and dermatologists regarding drug survival, reasons for
      withdrawal and safety. METHODS: Retrospective follow-up of all patients diagnosed
      with psoriasis by dermatologists or PsA by rheumatologists. Included were
      consecutive patients who started methotrexate (MTX) between 2006 and 2012 and had
      a scheduled follow-up by dermatologist or rheumatologist. Exclusions were: drug
      not started after the first prescription or incomplete availability of lab data.
      Data were extracted from electronic records: start and stop dates and dosing of
      MTX; treatment with folic acid and dose; reasons for withdrawal of MTX; numbers
      of blood sampling and types of laboratory tests performed for MTX safety; number
      of abnormal tests; occurrence of any serious adverse event (SAE). RESULTS: 190
      Psoriasis and 196 PsA patients starting methotrexate (MTX) were included. Age and
      sex were comparable. PsA patients used higher initial and maximum doses of MTX
      and folic acid, but psoriasis patients had a higher frequency of abnormal
      laboratory results (0.14 vs 0.03 per treatment month, p<0.001), resulting in a
      striking difference in withdrawal of MTX for abnormal liver enzymes (15.8% vs
      3.6%, p<0.001). In PsA patients MTX was withdrawn less frequently for
      ineffectiveness (15.8 vs 24.2%, p<0.05) leading to longer drug survival in the
      first course of treatment (37.4+/-30 vs 18.8+/-19.1 months). Repeated courses of
      MTX were more often prescribed by rheumatologists than by dermatologists. There
      were no significant differences in the occurrence of SAE (psoriasis 0.0041 vs PsA
      0.0038 per treatment month) or death (1.6% vs 2.0%) between these groups.
      Hospital admissions related to infection were recorded in 6 (3.1%) PsA vs 4
      (2.1%) psoriasis patients. CONCLUSION: Strict monitoring by dermatologists
      resulted in more abnormal findings, which reduced drug survival of MTX. The
      limited monitoring strategy by rheumatologists was not associated with more SAEs.
      Further research in other populations is needed to confirm whether reduced
      intensity of monitoring can optimize the use of MTX with sufficient long-term
      safety.

PMID- 29570707
TI  - Long-lived rodents reveal signatures of positive selection in genes associated
      with lifespan.
AB  - The genetics of lifespan determination is poorly understood. Most research has
      been done on short-lived animals and it is unclear if these insights can be
      transferred to long-lived mammals like humans. Some African mole-rats
      (Bathyergidae) have life expectancies that are multiple times higher than similar
      sized and phylogenetically closely related rodents. To gain new insights into
      genetic mechanisms determining mammalian lifespans, we obtained genomic and
      transcriptomic data from 17 rodent species and scanned eleven evolutionary
      branches associated with the evolution of enhanced longevity for positively
      selected genes (PSGs). Indicating relevance for aging, the set of 250 identified
      PSGs showed in liver of long-lived naked mole-rats and short-lived rats an
      expression pattern that fits the antagonistic pleiotropy theory of aging.
      Moreover, we found the PSGs to be enriched for genes known to be related to
      aging. Among these enrichments were "cellular respiration" and "metal ion
      homeostasis", as well as functional terms associated with processes regulated by
      the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs
      are RHEB, a regulator of mTOR, and IGF1, both central components of aging
      relevant pathways, as well as genes yet unknown to be aging-associated but
      representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and
      AGER. Exemplary protein homology modeling suggests functional consequences for
      amino acid changes under positive selection. Therefore, we conclude that our
      results provide a meaningful resource for follow-up studies to mechanistically
      link identified genes and amino acids under positive selection to aging and
      lifespan determination.

PMID- 29570709
TI  - Disentangling factors that shape the gut microbiota in German Shepherd dogs.
AB  - The aim of this study was to explore the development of the gut microbiota in 168
      German Shepherd dogs (30 litters) from 7 weeks to 18 months of age and
      furthermore, to study the effect of relatedness, maternal microbiota composition
      and living environment in a large and well-defined population of dogs. Using 454
      pyrosequencing, we assessed the effects of pre- and postnatal probiotic
      supplementation (Lactobacillus johnsonii NCC533 (La1)) and analysed whether
      administration of the probiotic strain influenced fecal microbiota composition in
      a placebo controlled double-blinded study. The bitches were treated with
      probiotics or placebo during last trimester of pregnancy and until their puppies
      were 8 weeks old, the puppies received the same treatment as their mothers
      between 3-12 weeks of age. Samples from bitches were collected at pregnancy day
      42, partum, 4 weeks postpartum and 7 weeks postpartum and from puppies at the age
      4 weeks, 7 weeks, 12-13 months and 15-18 months. Serum IgA, total serum IgE,
      fecal IgA and IgG antibody responses against canine distemper virus were analysed
      by ELISA in order to detect any immune stimulating effects of the probiotic
      strain. Analysis of the fecal microbiota composition showed that the predominant
      phyla were the same in 7 weeks old puppies as in pregnant and lactating bitches
      (Firmicutes, Fusobacteria, Bacteroidetes). Proportions among different bacteria
      as well as diversity varied from 7 weeks old puppies up to 15-18 months of age.
      Litter mates had a more similar fecal microbiota compared to unrelated dogs and 7
      weeks old puppies were more similar to their mothers than to unrelated bitches at
      7 weeks postpartum but not at partum. We observed a change in the relative
      abundance of different bacteria during lactation, and an increase in diversity
      from pregnancy to end of lactation. The microbial diversity was affected by
      living area where dogs living in big cities had higher diversity compared to dogs
      living at the countryside. However, we were not able to demonstrate an effect by
      pre and postnatal exposure to Lactobacillus johnsonii NCC533 (La1) upon the
      diversity or composition of the microbiota or the levels of serum IgA, total
      serum IgE, fecal IgA or vaccine response. Our findings provide a better
      understanding of the canine fecal microbiota in growing dogs as well as in
      pregnant and lactating bitches. This information forms a basis for further
      research on the connection between early gut colonization and immune function
      later in life.

PMID- 29570710
TI  - On the nature of real and perceived bias in the mainstream media.
AB  - News consumers expect news outlets to be objective and balanced in their reports
      of events and opinions. However, there is a growing body of evidence of bias in
      the media caused by underlying political and socio-economic viewpoints. Previous
      studies have tried to classify the partiality of the media, but there is little
      work on quantifying it, and less still on the nature of this partiality. The vast
      amount of content published in social media enables us to quantify the
      inclination of the press to pre-defined sides of the socio-political spectrum. To
      describe such tendencies, we use tweets to automatically compute a news outlet's
      political and socio-economic orientation. Results show that the media have a
      measurable bias, and illustrate this by showing the favoritism of Chilean media
      for the ruling political parties in the country. This favoritism becomes clearer
      as we empirically observe a shift in the position of the mass media when there is
      a change in government. Even though relative differences in bias between news
      outlets can be observed, public awareness of the bias of the media landscape as a
      whole appears to be limited by the political space defined by the news that we
      receive as a population. We found that the nature of the bias is reflected in the
      vocabulary used and the entities mentioned by different news outlets. A survey
      conducted among news consumers confirms that media bias has an impact on the
      coverage of controversial topics and that this is perceivable by the general
      audience. Having a more accurate method to measure and characterize media bias
      will help readers position outlets in the socio-economic landscape, even when a
      (sometimes opposite) self-declared position is stated. This will empower readers
      to better reflect on the content provided by their news outlets of choice.

PMID- 29570711
TI  - Smoking intensity and bladder cancer aggressiveness at diagnosis.
AB  - OBJECTIVE: To explore the relation between cigarette smoking intensity and
      bladder cancer aggressiveness at first diagnosis. METHODS: Patients diagnosed
      with urinary bladder cancer (BC) between 1995-2011 under the age of 75 years were
      retrospectively identified from the Netherlands Cancer Registry and invited for a
      study on genetic and lifestyle risk factors for BC. Information on patients' self
      reported smoking history was retrieved by means of a postal questionnaire. Tumors
      were stratified regarding the risk of progression defined by tumor stage and
      grade. Multinomial logistic regression was used to analyze the relation between
      smoking intensity and aggressiveness of the tumor. RESULTS: The UBC study
      population comprised 323 (17.4%) never smokers, 870 (46.8%) former cigarette
      smokers, and 630 (33.9%) current cigarette smokers. A higher smoking amount was a
      risk factor of getting high-risk non-muscle invasive bladder cancer (NMIBC)
      compared with low-risk NMIBC in ever and former cigarette smokers (OR: 1.02 per
      cigarette smoked, 95% CI: 1.00-1.03 and OR: 1.03, 95% CI: 1.01-1.05,
      respectively). A statistically significant dose-response increase in the risk of
      a more aggressive cancer type (high-risk NMIBC and MIBC) was observed with
      increasing smoking duration among former smokers (p for trend 0.035 and 0.008,
      respectively). No significant association of the evaluated smoking intensity
      variables was observed in current smokers. A longer time of smoking cessation
      correlated with a lower odds of a more aggressive cancer. CONCLUSION: We observed
      a weak increase in the risk of a more aggressive tumor type with increasing
      smoking intensity in former smokers, but this association was absent in current
      smokers. This conflicting result may suggest that there is no strong relation
      between smoking intensity and bladder cancer aggressiveness. Analyses of
      prospective studies with longitudinal smoking assessment may provide a more
      definitive answer to the research question.

PMID- 29570712
TI  - Shale gas activity and increased rates of sexually transmitted infections in
      Ohio, 2000-2016.
AB  - BACKGROUND: The growing shale gas ("fracking") industry depends on a mobile
      workforce, whose influx could have social impacts on host communities. Sexually
      transmitted infections (STIs) can increase through sexual mixing patterns
      associated with labor migration. No prior studies have quantified the
      relationship between shale gas activity and rates of three reportable STIs:
      chlamydia, gonorrhea, and syphilis. METHODS: We conducted a longitudinal,
      ecologic study from 2000-2016 in Ohio, situated in a prolific shale gas region in
      the United States (US). Data on reported cases of chlamydia, gonorrhea, and
      syphilis by county and year were obtained from the Ohio Department of Health. All
      88 counties were classified as none, low, and high shale gas activity in each
      year, using data from the Ohio Department of Natural Resources. Annual rate
      ratios (RR) and 95% confidence intervals (95% CIs) were calculated from mixed
      effects Poisson regression models evaluating the relationship between shale gas
      activity and reported annual STI rates while adjusting for secular trends and
      potential confounders obtained from the US Census. RESULTS: Compared to counties
      with no shale gas activity, counties with high activity had 21% (RR = 1.21; 95%CI
      = 1.08-1.36) increased rates of chlamydia and 19% (RR = 1.27; 95%CI 0.98-1.44)
      increased rates of gonorrhea, respectively. No association was observed for
      syphilis. CONCLUSION: This first report of a link between shale gas activity and
      increased rates of both chlamydia and gonorrhea may inform local policies and
      community health efforts.

PMID- 29570713
TI  - Maternal, fetal and perinatal factors associated with necrotizing enterocolitis
      in Sweden. A national case-control study.
AB  - OBJECTIVE: To analyze associations of maternal, fetal, gestational, and perinatal
      factors with necrotizing enterocolitis in a matched case-control study based on
      routinely collected, nationwide register data. STUDY DESIGN: All infants born in
      1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the
      Swedish national health care registers were identified. For each case up to 6
      controls, matched for birth year and gestational age, were selected. The
      resulting study population consisted of 720 cases and 3,567 controls. Information
      on socioeconomic data about the mother, maternal morbidity, pregnancy related
      diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal
      period, was obtained for all cases and controls and analyzed with univariable and
      multivariable logistic regressions for the whole study population as well as for
      subgroups according to gestational age. RESULTS: In the study population as a
      whole, we found independent positive associations with necrotizing enterocolitis
      for isoimmunization, fetal distress, cesarean section, neonatal bacterial
      infection including sepsis, erythrocyte transfusion, persistent ductus
      arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal
      abnormality. Negative associations were found for maternal weight, preeclampsia,
      maternal urinary infection, premature rupture of the membranes, and birthweight.
      Different patterns of associations were seen in the subgroups of different
      gestational age. CONCLUSION: With some interesting exceptions, especially in
      negative associations, the results of this large, population based study, are in
      keeping with earlier studies. Although restrained by the limitations of register
      data, the findings mirror conceivable pathophysiological processes and underline
      that NEC is a multifactorial disease.

PMID- 29570714
TI  - Nascent RNA signaling to yeast RNA Pol II during transcription elongation.
AB  - Transcription as the key step in gene expression is a highly regulated process.
      The speed of transcription elongation depends on the underlying gene sequence and
      varies on a gene by gene basis. The reason for this sequence dependence is not
      known in detail. Recently, our group studied the cross talk between the nascent
      RNA and the transcribing RNA polymerase by screening the Escherichia coli genome
      for RNA sequences with high affinity to RNA Pol by performing genomic SELEX. This
      approach led to the identification of RNA polymerase-binding APtamers termed
      "RAPs". RAPs can have positive and negative effects on gene expression. A
      subgroup is able to downregulate transcription via the activity of the
      termination factor Rho. In this study, we used a similar SELEX setup using yeast
      genomic DNA as source of RNA sequences and highly purified yeast RNA Pol II as
      bait and obtained almost 1300 yeast-derived RAPs. Yeast RAPs are found throughout
      the genome within genes and antisense to genes, they are overrepresented in the
      non-transcribed strand of yeast telomeres and underrepresented in intergenic
      regions. Genes harbouring a RAP are more likely to show lower mRNA levels. By
      determining the endogenous expression levels as well as using a reporter system,
      we show that RAPs located within coding regions can reduce the transcript level
      downstream of the RAP. Here we demonstrate that RAPs represent a novel type of
      regulatory RNA signal in Saccharomyces cerevisiae that act in cis and interfere
      with the elongating transcription machinery to reduce the transcriptional output.

PMID- 29570715
TI  - Preoperative statins are associated with a reduced risk of postoperative delirium
      following vascular surgery.
AB  - Delirium is a common complication of vascular surgery. The protective effect of
      preoperative statins on delirium after vascular surgery is controversial. The
      authors hypothesized that preoperative statin administration would decrease the
      incidence of delirium after vascular surgery. From May 2010 to May 2015, 1,132
      patients underwent vascular surgery. Postoperative delirium was diagnosed from
      patients' medical records. The incidence of delirium was 11.5%. The preoperative
      statin exposure was not associated with reduced delirium in the univariate
      analysis. After adjusting for covariates, preoperative statin exposure was
      associated with reduced delirium (OR, 0.54; 95% CI, 0.33-0.87; p = 0.011). This
      favor effect of statin for delirium was observed after propensity matching (OR,
      0.59; 95% CI, 0.34-1.02; p = 0.060). However, the median hospital lengths of stay
      and in-hospital mortality were not statistically different between the two
      groups. CRP(C-reactive protein) levels in the unmatched population were lower in
      the preoperative statin group compared with the other group (p<0.001), however,
      there was only numerically different without statistical difference after
      matching (p = 0.083). Preoperative statin use was associated with a decreased
      incidence of postoperative delirium in patients who underwent vascular surgery.
      However, preoperative statin did not reduce mortality rate and hospital stay.

PMID- 29570716
TI  - The long-range interaction map of ribosomal DNA arrays.
AB  - The repeated rDNA array gives rise to the nucleolus, an organelle that is central
      to cellular processes as varied as stress response, cell cycle regulation, RNA
      modification, cell metabolism, and genome stability. The rDNA array is also
      responsible for the production of more than 70% of all cellular RNAs (the
      ribosomal RNAs). The rRNAs are produced from two sets of loci: the 5S rDNA array
      resides exclusively on human chromosome 1 while the 45S rDNA arrays reside on the
      short arm of five human acrocentric chromosomes. These critical genome elements
      have remained unassembled and have been excluded from all Hi-C analyses to date.
      Here we built the first high resolution map of 5S and 45S rDNA array contacts
      with the rest of the genome combining over 15 billion Hi-C reads from several
      experiments. The data enabled sufficiently high coverage to map rDNA-genome
      interactions with 1MB resolution and identify rDNA-gene contacts. The map showed
      that the 5S and 45S arrays display preferential contact at common sites along the
      genome but are not themselves sufficiently close to yield 5S-45S Hi-C contacts.
      Ribosomal DNA contacts are enriched in segments of closed, repressed, and late
      replicating chromatin, as well as CTCF binding sites. Finally, we identified
      functional categories whose dispersed genes coalesced in proximity to the rDNA
      arrays or instead avoided proximity with the rDNA arrays. The observations
      further our understanding of the spatial localization of rDNA arrays and their
      contribution to the architecture of the cell nucleus.

PMID- 29570717
TI  - Population dynamics of engineered underdominance and killer-rescue gene drives in
      the control of disease vectors.
AB  - A number of different genetics-based vector control methods have been proposed.
      Two approaches currently under development in Aedes aegypti mosquitoes are the
      two-locus engineered underdominance and killer-rescue gene drive systems. Each of
      these is theoretically capable of increasing in frequency within a population,
      thus spreading associated desirable genetic traits. Thus they have gained
      attention for their potential to aid in the fight against various mosquito
      vectored diseases. In the case of engineered underdominance, introduced
      transgenes are theoretically capable of persisting indefinitely (i.e. it is self
      sustaining) whilst in the killer-rescue system the rescue component should
      initially increase in frequency (while the lethal component (killer) is common)
      before eventually declining (when the killer is rare) and being eliminated (i.e.
      it is temporally self-limiting). The population genetics of both systems have
      been explored using discrete generation mathematical models. The effects of
      various ecological factors on these two systems have also been considered using
      alternative modelling methodologies. Here we formulate and analyse new
      mathematical models combining the population dynamics and population genetics of
      these two classes of gene drive that incorporate ecological factors not
      previously studied and are simple enough to allow the effects of each to be
      disentangled. In particular, we focus on the potential effects that may be
      obtained as a result of differing ecological factors such as strengths of larval
      competition; numbers of breeding sites; and the relative fitness of transgenic
      mosquitoes compared with their wild-type counterparts. We also extend our models
      to consider population dynamics in two demes in order to explore the effects of
      dispersal between neighbouring populations on the outcome of UD and KR gene drive
      systems.

PMID- 29570718
TI  - Taxonomic revision of Chloromonas nivalis (Volvocales, Chlorophyceae) strains,
      with the new description of two snow-inhabiting Chloromonas species.
AB  - Chloromonas nivalis (Volvocales, Chlorophyceae) is considered a cosmopolitan
      species of a snow-inhabiting microalga because cysts morphologically identifiable
      as zygotes of the species are distributed worldwide. However, recent molecular
      data demonstrated that field-collected cysts identified as the zygotes consist of
      multiple species. Recently, we demonstrated that species identification of snow
      inhabiting Chloromonas species is possible based on light and electron microscopy
      of asexual life cycles in strains and molecular phylogenetic analyses. Vegetative
      cells without eyespots and of inverted-teardrop shape have been reported once in
      North American material of C. nivalis; however, strains with such vegetative
      cells in snow-inhabiting species of Chloromonas have not been examined
      taxonomically in detail. Here, we used light and transmission electron microscopy
      together with molecular analyses of multiple DNA sequences to examine several C.
      nivalis strains. The morphological data demonstrated that one North American
      strain could be identified as C. nivalis, whereas three other strains should be
      re-classified as C. hoshawii sp. nov. and C. remiasii sp. nov. based on
      vegetative cell morphology, the number of zoospores within the parental cell wall
      during asexual reproduction, and whether cell aggregates (resulting from repeated
      divisions of daughter cells retained within a parental cell wall) were observed
      in the culture. This taxonomic treatment was supported by multigene phylogeny and
      comparative molecular analyses that included a rapidly evolving DNA region. Our
      molecular phylogenetic analyses also demonstrated that the North American strain
      of C. nivalis was phylogenetically separated from the Austrian and Japanese
      specimens previously identified as C. nivalis based on zygote morphology.

PMID- 29570720
TI  - The double burden of disease and the challenge of health access: Evidence from
      Access, Bottlenecks, Cost and Equity facility survey in Ghana.
AB  - Despite the double burden of infectious and chronic non-communicable diseases in
      Africa, health care expenditure disproportionately favours infectious diseases.
      In this paper, we examine quantitatively the extent of this disproportionate
      access to diagnoses and treatment of diabetes, hypertension and malaria in Ghana.
      A total of 220 health facilities was surveyed across the country in 2011.
      Findings indicate that diagnoses and treatment of infectious diseases were more
      accessible than NCDs. In terms of treatment, 78% and 87% of health facilities had
      two of the recommended malaria drugs while less than 35% had essential diabetes
      and hypertension drugs. There is a significant unmet need for diagnoses and
      treatment of NCDs in Ghana. These inequities have implications for high morbidity
      and mortality from NCDs. We recommend the use of task shifting as a model to
      increase the delivery of NCD services.

PMID- 29570719
TI  - Avian viral surveillance in Victoria, Australia, and detection of two novel avian
      herpesviruses.
AB  - Viruses in avian hosts can pose threats to avian health and some have zoonotic
      potential. Hospitals that provide veterinary care for avian patients may serve as
      a site of exposure of other birds and human staff in the facility to these
      viruses. They can also provide a useful location to collect samples from avian
      patients in order to examine the viruses present in wild birds. This study aimed
      to investigate viruses of biosecurity and/or zoonotic significance in Australian
      birds by screening samples collected from 409 birds presented to the Australian
      Wildlife Health Centre at Zoos Victoria's Healesville Sanctuary for veterinary
      care between December 2014 and December 2015. Samples were tested for avian
      influenza viruses, herpesviruses, paramyxoviruses and coronaviruses, using genus-
      or family-wide polymerase chain reaction methods coupled with sequencing and
      phylogenetic analyses for detection and identification of both known and novel
      viruses. A very low prevalence of viruses was detected. Columbid alphaherpesvirus
      1 was detected from a powerful owl (Ninox strenua) with inclusion body hepatitis,
      and an avian paramyxovirus most similar to Avian avulavirus 5 was detected from a
      musk lorikeet (Glossopsitta concinna). Two distinct novel avian
      alphaherpesviruses were detected in samples from a sulphur-crested cockatoo
      (Cacatua galerita) and a tawny frogmouth (Podargus strigoides). Avian influenza
      viruses and avian coronaviruses were not detected. The clinical significance of
      the newly detected viruses remains undetermined. Further studies are needed to
      assess the host specificity, epidemiology, pathogenicity and host-pathogen
      relationships of these novel viruses. Further genome characterization is also
      indicated, and would be required before these viruses can be formally classified
      taxonomically. The detection of these viruses contributes to our knowledge on
      avian virodiversity. The low level of avian virus detection, and the absence of
      any viruses with zoonotic potential, suggests low risk to biosecurity and human
      health.

PMID- 29570721
TI  - Structural and functional analyses of the optic nerve and lateral geniculate
      nucleus in glaucoma.
AB  - PURPOSE: To analyze the correlation between structural characteristics of
      intraorbital optic nerve (ION) and lateral geniculate nucleus (LGN) measured by 3
      Tesla magnetic resonance imaging (3T MRI), and the severity of glaucomatous
      damage. METHODS: In this cross-sectional study, 41 glaucoma patients and 12 age-
      and sex-matched controls underwent standard automated perimetry (SAP) and
      frequency doubling technology (FDT) as functional evaluation; optic disc
      stereophotograph, spectral-domain optical coherence tomography (OCT) and confocal
      scanning laser tomography as ocular structural evaluation; and 3T MRI. Structure
      structure and structure-function correlation were performed using bootstrap
      resampling method for clustered data. RESULTS: The ION mean diameter and cross
      sectional area were different between glaucoma and control groups at 5mm and 10mm
      (all, p<=0.011) from the globe, but not at 15mm (both, p>=0.067). LGN height was
      significantly lower in glaucoma group (p = 0.005). OCT rim area and functional
      parameters (SAP and FDT) correlated significantly with all ION segments, showing
      stronger correlations at 10 and 15 mm. ION parameters at 10 and 15 mm presented
      mild-to-moderate correlation with OCT peripapillary nerve fiber layer thickness,
      and ION at 15mm had mild association with the neuroretinal rim area on
      stereophotographs. Although LGN height was significantly smaller in glaucoma
      group (p = 0.005), LGN parameters were not associated with any ocular structural
      or functional parameter. CONCLUSION: Assessment of central and peripheral nervous
      systems using 3T MRI confirmed that glaucoma patients had smaller ION dimensions
      and LGN height compared to the control group. In general, ION dimensions
      presented mild to moderate correlations with functional and ocular structural
      parameters. Although ION had significant correlations at any distance from the
      eye, the ION distal locations correlated better with OCT results and functional
      parameters. However, LGN parameters were not associated with functional or ocular
      structural parameters.

PMID- 29570722
TI  - Thoracic dysfunction in whiplash associated disorders: A systematic review.
AB  - BACKGROUND: Research investigating Whiplash Associated Disorder (WAD) has largely
      focused on the cervical spine yet symptoms can be widespread. Thoracic spine pain
      prevalence is reported ~66%; perhaps unsurprising given the forceful
      stretch/eccentric loading of posterior structures of the spine, and the thoracic
      spine's contribution to neck mobility/function. Approximately 50% WAD patients
      develop chronic pain and disability resulting in high levels of societal and
      healthcare costs. It is time to look beyond the cervical spine to fully
      understand anatomical dysfunction in WAD and provide new directions for clinical
      practice and research. PURPOSE: To evaluate the scope and nature of dysfunction
      in the thoracic region in patients with WAD. METHODS: A systematic review and
      data synthesis was conducted according to a pre-defined, registered (PROSPERO,
      CRD42015026983) and published protocol. All forms of observational study were
      included. A sensitive topic-based search strategy was designed from inception to
      1/06/16. Databases, grey literature and registers were searched using a study
      population terms and key words derived from scoping search. Two reviewers
      independently searched information sources, assessed studies for inclusion,
      extracted data and assessed risk of bias. A third reviewer checked for
      consistency and clarity. Extracted data included summary data: sample size and
      characteristics, outcomes, and timescales to reflect disorder state. Risk of bias
      was assessed using the Newcastle-Ottawa Scale. Data were tabulated to allow
      enabling a semi-qualitative comparison and grouped by outcome across studies.
      Strength of the overall body of evidence was assessed using a modified GRADE.
      RESULTS: Thirty eight studies (n>50,000) which were conducted across a range of
      countries were included. Few authors responded to requests for further data (5 of
      9 contacted). Results were reported in the context of overall quality and were
      presented for measures of pain or dysfunction and presented, where possible,
      according to WAD severity and time point post injury. Key findings include: 1)
      high prevalence of thoracic pain (>60%); higher for those with more severe
      presentations and in the acute stage, 2) low prevalence of chest pain (<22%), 3)
      evidence of thoracic outlet syndrome, with some association to and involvement of
      the brachial plexus, 4) muscle dysfunction in the form of heightened activity of
      the sternocleidomastoid or delayed onset of action of the serratus anterior, 5)
      high prevalence of myofascial pain and trigger points in the scalene muscles,
      sternocleidomastoid and mid/lower fibres of trapezius muscle (48-65%), and 6)
      inconclusive evidence of altered thoracic posture or mobility. CONCLUSIONS:
      Considerable evidence supports thoracic pain and dysfunction in patients with
      WAD, involving primarily nerves and muscles. Notwithstanding the low/very low
      level of evidence from this review, our findings do support a more extensive
      clinical evaluation of patients presenting with WAD. Additional high quality
      research is required to further characterise dysfunction across other structures
      in the thoracic region, including but not limited to the thoracic spine (mobility
      and posture) and thoracic muscles (stiffness, activation patterns). In turn this
      may inform the design of clinical trials targeting such dysfunction.

PMID- 29570723
TI  - HIV treatment eligibility expansion and timely antiretroviral treatment
      initiation following enrollment in HIV care: A metaregression analysis of
      programmatic data from 22 countries.
AB  - BACKGROUND: The effect of antiretroviral treatment (ART) eligibility expansions
      on patient outcomes, including rates of timely ART initiation among those
      enrolling in care, has not been assessed on a large scale. In addition, it is not
      known whether ART eligibility expansions may lead to "crowding out" of sicker
      patients. METHODS AND FINDINGS: We examined changes in timely ART initiation
      (within 6 months) at the original site of HIV care enrollment after ART
      eligibility expansions among 284,740 adult ART-naive patients at 171
      International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22
      countries where national policies expanding ART eligibility were introduced
      between 2007 and 2015. Half of the sites included in this analysis were from
      Southern Africa, one-third were from East Africa, and the remainder were from the
      Asia-Pacific, Central Africa, North America, and South and Central America
      regions. The median age of patients enrolling in care at contributing sites was
      33.5 years, and the median percentage of female patients at these clinics was
      62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI
      ART) before and after major expansions of ART eligibility (i.e., expansion to
      treat persons with CD4 <= 350 cells/MUL [145 sites in 22 countries] and CD4 <=
      500 cells/MUL [152 sites in 15 countries]). Random effects metaregression models
      were used to estimate absolute changes in CI-ART at each site before and after
      guideline expansion. The crude pooled estimate of change in CI-ART was 4.3
      percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility
      expansion to CD4 <= 350, from a baseline median CI-ART of 53%; and 15.9
      percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to
      CD4 <= 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART
      were observed among those newly eligible for treatment (18.2 pp after expansion
      to CD4 <= 350 and 47.4 pp after expansion to CD4 <= 500), with no change or small
      increases among those eligible under prior guidelines (CD4 <= 350: -0.6 pp, 95%
      CI -2.0 to 0.7 pp; CD4 <= 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility
      expansion to CD4 <= 500, changes in CI-ART were largest among younger patients
      (16-24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack
      of a counterfactual and difficulty accounting for secular outcome trends, due to
      universal exposure to guideline changes in each country. CONCLUSIONS: These
      findings underscore the potential of ART eligibility expansion to improve the
      timeliness of ART initiation globally, particularly for young adults.

PMID- 29570725
TI  - Retraction: A wireless soil moisture sensor powered by solar energy.

PMID- 29570724
TI  - Predictors of long term weight loss maintenance in patients at high risk of type
      2 diabetes participating in a lifestyle intervention program in primary health
      care: The DE-PLAN study.
AB  - Lifestyle interventions in type 2 diabetes (DM2) prevention implementation
      studies can be effective and lasting. Long-term weight loss maintenance enhances
      the intervention effect through a significant decrease in diabetes incidence over
      time. Our objective was to identify factors predicting long-term successful
      weight reduction maintenance achieved during a DM2 prevention program in patients
      with high DM2 risk in primary health care. Study participants (n = 263), middle
      aged, slightly obese with baseline increased DM2 risk (Finnish Diabetes Risk
      Score (FINDRISC)>14), but no diabetes were invited to receive 11 lifestyle
      counselling sessions, guided physical activity sessions and motivational support
      during 10-months. The study participants had three clinical examinations during
      the study (baseline, one and three years). Stepwise regression analysis was used
      to determine demographic, clinical, and lifestyle predictors of weight reduction
      maintenance two years after the discontinuation of the intervention. Out of 105
      patients who completed all three examinations (baseline age 56.6 (standard
      deviation (SD) = 10.7), body mass index 31.1 kg/m2 (SD = 4.9), FINDRISC 18.6 (SD
      = 3.1)), 73 patients (70%) showed weight loss during the intervention (mean
      weight loss 4.2 kg, SD = 5.1). The total weight loss achieved in the maintainers
      (27 of 73 study participants) two years after the intervention had finished was
      6.54 kg (4.47 kg+2.0 kg). The non-maintainers, on the other hand, returned to
      their initial weight at the start of the intervention (+0.21 kg). In
      multivariable analysis baseline history of increased glucose (odds ratio (OR) =
      3.7; 95% confidence interval (CI) 1.0-13.6) and reduction of total fat in diet
      during follow-up (OR = 4.3; 95% CI 1.5-12.2) were independent predictors of
      successful weight loss. Further studies exploring predictors of weight loss
      maintenance in diabetes prevention are needed to help health care providers to
      redesign interventions and improve long-term outcomes of real life interventions.

PMID- 29570726
TI  - Time for high-burden countries to lead the tuberculosis research agenda.
AB  - In a Guest Editorial, Madhukar Pai discusses the need for high-burden burden,
      middle-income countries to take a leading role in tuberculosis research.

PMID- 29570727
TI  - miR-126-5p by direct targeting of JNK-interacting protein-2 (JIP-2) plays a key
      role in Theileria-infected macrophage virulence.
AB  - Theileria annulata is an apicomplexan parasite that infects and transforms bovine
      macrophages that disseminate throughout the animal causing a leukaemia-like
      disease called tropical theileriosis. Using deep RNAseq of T. annulata-infected B
      cells and macrophages we identify a set of microRNAs induced by infection, whose
      expression diminishes upon loss of the hyper-disseminating phenotype of virulent
      transformed macrophages. We describe how infection-induced upregulation of miR
      126-5p ablates JIP-2 expression to release cytosolic JNK to translocate to the
      nucleus and trans-activate AP-1-driven transcription of mmp9 to promote tumour
      dissemination. In non-disseminating attenuated macrophages miR-126-5p levels
      drop, JIP-2 levels increase, JNK1 is retained in the cytosol leading to decreased
      c-Jun phosphorylation and dampened AP-1-driven mmp9 transcription. We show that
      variation in miR-126-5p levels depends on the tyrosine phosphorylation status of
      AGO2 that is regulated by Grb2-recruitment of PTP1B. In attenuated macrophages
      Grb2 levels drop resulting in less PTP1B recruitment, greater AGO2
      phosphorylation, less miR-126-5p associated with AGO2 and a consequent rise in
      JIP-2 levels. Changes in miR-126-5p levels therefore, underpin both the virulent
      hyper-dissemination and the attenuated dissemination of T. annulata-infected
      macrophages.

PMID- 29570728
TI  - At-hatch administration of probiotic to chickens can introduce beneficial changes
      in gut microbiota.
AB  - Recent advances in culture-free microbiological techniques bring new
      understanding of the role of intestinal microbiota in heath and performance.
      Intestinal microbial communities in chickens assume a near-stable state within
      the week which leaves a very small window for permanent microbiota remodelling.
      It is the first colonisers that determine the fate of microbial community in
      humans and birds alike, and after the microbiota has matured there are very small
      odds for permanent modification as stable community resists change. In this study
      we inoculated broiler chicks immediately post hatch, with 3 species of
      Lactobacillus, identified by sequencing of 16S rRNA and pheS genes as L.
      ingluviei, L. agilis and L. reuteri. The strains were isolated from the gut of
      healthy chickens as reproducibly persistent Lactobacillus strains among multiple
      flocks. Birds inoculated with the probiotic mix reached significantly higher
      weight by 28 days of age. Although each strain was able to colonise when
      administered alone, administering the probiotic mix at-hatch resulted in
      colonisation by only L. ingluviei. High initial abundance of L. ingluviei was
      slowly reducing, however, the effects of at-hatch administration of the
      Lactobacillus mix on modifying microbiota development and structure remained
      persistent. There was a tendency of promotion of beneficial and reduction in
      pathogenic taxa in the probiotic administered group.

PMID- 29570729
TI  - Expand your body when you look at yourself: The role of the posture in a mirror
      exposure task.
AB  - Mirror exposure (ME) is one of the main components of the treatment of patients
      with eating disorders symptomatology and it has shown its effectiveness in
      improving several outcomes (e.g., body dissatisfaction). However, the study as to
      what body posture should be adopted to maximize its effectiveness has been
      neglected. From embodied cognition and emotion theories, the adoption of an
      expansive (vs. contractive) body posture has been associated with positive
      changes in cognitive and emotional responses. The objective of this study was to
      analyze the effect of adopting an expansive (vs. contractive) posture before an
      ME task on body-related emotions and cognitions, as well as to analyze the
      possible moderator and mediator variables of these relationships. The sample was
      composed of 68 women (age: M = 21.74, SD = 3.12) with high scores on body
      dissatisfaction. Participants were randomly assigned to the expansive or
      contractive condition, where the openness of the arms/legs and the back position
      were manipulated. Posture was monitored by an electronic device and participants
      filled out several self-reported measures. ANCOVAs, moderation, mediation, and
      moderated mediated analyses were performed. Results showed that women in the
      expansive condition showed higher positive emotions after the ME. Moreover,
      exploratory analyses showed that adopting an expansive posture improved positive
      emotions, leading to improvements in negative emotions, body image satisfaction,
      and appraisal of the person's own body. Psychological interventions should
      explore the value of holding an expansive posture before the ME in women with
      body dissatisfaction.

PMID- 29570730
TI  - Risk of heavy metal ingestion from the consumption of two commercially valuable
      species of fish from the fresh and coastal waters of Ghana.
AB  - BACKGROUND: The need to evaluate the human health safety of fishery resources
      remain urgent in the mist of the ever-increasing fear of heavy metal toxicity
      from the consumption of Ghana's fisheries resource, as a consequence of pollution
      from several anthropogenic activities including artisanal gold mining.
      Nevertheless, the bigeye grunt (Brachydeuterus auritus) and Bagrid catfish
      (Chrysichthys nigrodigitatus) remain commercially valuable fish species in West
      Africa and continue to attract high patronage. METHOD: Forty-five specimens each
      of C. nigrodigitatus and B. auritus collected from the Weija Dam and the Tema
      Fishing Habour in Ghana, between June and September 2016, were analysed for seven
      heavy metals using Atomic Absorption Spectrometry. RESULT: Lead and Cadmium were
      below detection in all samples while Cu was not detected in B. auritus. Levels of
      the remaining metals (mg kg-1) were below FAO/WHO maximum permissible limits in
      fish and occurred in the rank order Se (3.5) > Zn (2.34) > Cu (0.59) > As (0.37)
      > Hg (0.19) in C. nigrodigitatus and Se (2.97) > Zn (2.28) > Hg (0.31) > As
      (0.21) in B. auritus. Only As in C. nigrodigitatus recorded Estimated Weekly
      Intake (EWI) greater than FAO/WHO Provisional Tolerable Weekly Intake (PTWI).
      Also, As in C. nigrodigitatus and Hg in B. auritus had Targeted Hazard Quotient
      (THQ) greater than 1 for individuals consuming the fishes on daily basis and
      therefore, raising concerns. However, for both species of fish, cancer risk of As
      was 1 in 10,000,000,000 and modified Health Benefits values of Se (HBVSe) were
      positive indicating the health risks that might accompany Hg exposure would be
      negated. Since toxicity depends on the concentration and quantity of a pollutant
      consumed, safe maximum consumption rate of C. nigrodigitatus based on As
      concentrations was 0.21 mg per day and that of B. auritus was 0.058 mg per day
      for Hg. With an average of 0.227 kg fish per meal of an adult human, these
      translated into not more than 24 C. nigrodigitatus and nine (9) B. auritus meals
      in a month but because fish is consumed at 0.0685 kg per person per day in Ghana,
      these values respectively translates to 93 and 30 safe days of consumption per
      month. CONCLUSION: At the rate of 0.0685 kg fish per person per day that fish is
      consumed in Ghana, the consumption of the two species of fish in Ghana would
      essentially be of little or no consequence to consumers.

PMID- 29570731
TI  - Anxa2 attenuates osteoblast growth and is associated with hip BMD and
      osteoporotic fracture in Chinese elderly.
AB  - Low bone mineral density (BMD) is a risk factor of osteoporotic fracture (OF).
      Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb
      bone. It was known that PBM-expressed Anxa2 protein is associated with BMD, and
      extracellular Anxa2 protein promotes osteoclastogenesis. This study aimed to test
      1) whether Anxa2 protein level in PBM differs significantly between subjects with
      OF and without fracture history (NF); 2) whether Anxa2 level in plasma is
      associated with BMD; 3) how Anxa2 protein at various concentrations would affect
      osteoblastic activity in vitro. All the study subjects were Chinese Han elderly.
      Firstly, Anxa2 protein in PBM was identified and quantitated by LC-MS/MS and
      compared between 45 OF cases and 42 healthy controls. Secondly, plasma Anxa2
      protein level was quantitated by ELISA and compared between unrelated subjects
      with extremely low vs. high hip BMD (0.63+/-0.10 vs. 1.05+/-0.10 g/cm2, n = 75).
      Furthermore, in vitro functional assay was utilized to test the effects of
      extracellular Anxa2 protein on osteoblastic growth. We found that Anxa2 protein
      expression in PBM was significantly up-regulated in OF vs. NF subjects (fold
      change [FC)] = 1.16, P<0.05). Plasma Anxa2 protein concentration (range: 31.69
      227.35ng/ml) was significantly elevated in low vs. high BMD subjects (84.85 vs.
      66.15ng/ml, FC = 1.28, P<0.05). Cellular dynamical monitoring demonstrated that
      the general shape of dose-response relationship is the inverse U-shaped curve.
      Specifically, lower dose of Anxa2 protein may promote osteoblast growth and the
      optimal concentration for osteoblastic growth was around 50ng/ml, but even higher
      concentration could attenuate hFOB1.19 osteoprogenitor cell growth. We concluded
      that Anxa2 protein could attenuate osteoblast growth and be associated with hip
      BMD and OF in Chinese elderly.

PMID- 29570732
TI  - Discovery of ancient Roman "highway" reveals geomorphic changes in karst
      environments during historic times.
AB  - Sinkholes are a well-known geologic hazard but their past occurrence, useful for
      subsidence risk prediction, is difficult to define, especially for ancient
      historic times. Consequently, our knowledge about Holocene carbonate landscapes
      is often limited. A multidisciplinary study of Trieste Karst (Italy), close to
      early Roman military fortifications, led to the identification of possible
      ancient road tracks, cut by at least one sinkhole. Electrical Resistivity
      Tomography through the sinkhole has suggested the presence of a cave below its
      bottom, possibly responsible of the sinkhole formation, while Ground Penetrating
      Radar has detected no tectonic disturbances underneath the tracks. Additionally,
      archaeological surveys led to the discovery of over 200 Roman shoe hobnails
      within or close to the investigated route. According to these data, the tracks
      are interpreted as the remains of a main Roman road, whose itinerary has been
      reconstructed for more than 4 km together with other elements of ancient
      landscape. Our results provide the first known evidence of a Roman main road
      swallowed by sinkholes and suggest that Holocene karst landscapes could be much
      different from what previously believed. In fact, sinkholes visible nowadays in
      the investigated region could have been flat areas filled by sediments up to the
      Roman time.

PMID- 29570733
TI  - Ribosome profiling reveals changes in translational status of soybean transcripts
      during immature cotyledon development.
AB  - To understand translational capacity on a genome-wide scale across three
      developmental stages of immature soybean seed cotyledons, ribosome profiling was
      performed in combination with RNA sequencing and cluster analysis. Transcripts
      representing 216 unique genes demonstrated a higher level of translational
      activity in at least one stage by exhibiting higher translational efficiencies
      (TEs) in which there were relatively more ribosome footprint sequence reads
      mapping to the transcript than were present in the control total RNA sample. The
      majority of these transcripts were more translationally active at the early stage
      of seed development and included 12 unique serine or cysteine proteases and 16 2S
      albumin and low molecular weight cysteine-rich proteins that may serve as
      substrates for turnover and mobilization early in seed development. It would
      appear that the serine proteases and 2S albumins play a vital role in the early
      stages. In contrast, our investigation of profiles of 19 genes encoding high
      abundance seed storage proteins, such as glycinins, beta-conglycinins, lectin,
      and Kunitz trypsin inhibitors, showed that they all had similar patterns in which
      the TE values started at low levels and increased approximately 2 to 6-fold
      during development. The highest levels of these seed protein transcripts were
      found at the mid-developmental stage, whereas the highest ribosome footprint
      levels of only up to 1.6 TE were found at the late developmental stage. These
      experimental findings suggest that the major seed storage protein coding genes
      are primarily regulated at the transcriptional level during normal soybean
      cotyledon development. Finally, our analyses also identified a total of 370
      unique gene models that showed very low TE values including over 48 genes
      encoding ribosomal family proteins and 95 gene models that are related to energy
      and photosynthetic functions, many of which have homology to the chloroplast
      genome. Additionally, we showed that genes of the chloroplast were relatively
      translationally inactive during seed development.

PMID- 29570734
TI  - Characterization of the adult Aedes aegypti early midgut peritrophic matrix
      proteome using LC-MS.
AB  - The Aedes aegypti mosquito is the principal vector of arboviruses such as dengue,
      chikungunya, yellow fever, and Zika virus. These arboviruses are transmitted
      during adult female mosquito bloodfeeding. While these viruses must transverse
      the midgut to replicate, the blood meal must also reach the midgut to be
      digested, absorbed, or excreted, as aggregation of blood meal metabolites can be
      toxic to the female mosquito midgut. The midgut peritrophic matrix (PM), a
      semipermeable extracellular layer comprised of chitin fibrils, glycoproteins, and
      proteoglycans, is one such mechanism of protection for the mosquito midgut.
      However, this structure has not been characterized for adult female Ae. aegypti.
      We conducted a mass spectrometry based proteomic analysis to identify proteins
      that comprise or are associated with the adult female Ae. aegypti early midgut
      PM. Altogether, 474 unique proteins were identified, with 115 predicted as
      secreted. GO-term enrichment analysis revealed an abundance of serine-type
      proteases and several known and novel intestinal mucins. In addition,
      approximately 10% of the peptides identified corresponded to known salivary
      proteins, indicating Ae. aegypti mosquitoes extensively swallow their own
      salivary secretions. However, the physiological relevance of this remains
      unclear, and further studies are needed to determine PM proteins integral for
      midgut protection from blood meal derived toxicity and pathogen protection.
      Finally, we describe substantial discordance between previously described
      transcriptionally changes observed in the midgut in response to a bloodmeal and
      the presence of the corresponding protein in the PM. Data are available via
      ProteomeXchange with identifier PXD007627.

PMID- 29570736
TI  - Medical expenditure and unmet need of the pre-elderly and the elderly according
      to job status in Korea: Are the elderly indeed most vulnerable?
AB  - Increase in the elderly population and early retirement imposes immense economic
      burden on societies. Previous studies on the association between medical
      expenditure and working status in the elderly population have not adequately
      addressed reverse causality problem. In addition, the pre-elderly group has
      hardly been discussed in this regard. This study assessed possible causal
      association between employment status and medical expenditure as well as
      employment status and medical unmet needs in a representative sample of the
      Korean elderly (aged?65) and the pre-elderly (aged ?50 and < 65) adults from the
      Korea Health Panel Data (KHP). Dynamic panel Generalized Method of Moments (GMM)
      estimation was employed for the analysis of medical expenditure to address
      reverse causality, and fixed effect panel logistic regression was used for the
      analysis of unmet need. The results showed no significant association between job
      status and medical expenditure in the elderly, but a negative and significant
      influence on the level of medical expenditure in the pre-elderly. Unemployment
      was a significant determinant of lowering unmet need from lack of time while it
      was not associated with unmet need from financial burden in the fixed-effect
      panel model for both the elderly and pre-elderly groups. The pre-elderly adults
      were more likely to reduce necessary health service utilization due to
      unemployment compared to the elderly group because there is no proper financial
      safety net for the pre-elderly, which may cause non-adherence to treatment and
      therefore lead to negative health effects. The policy dialogue on safety net
      currently centers only on the elderly, but should be extended to the pre-elderly
      population.

PMID- 29570735
TI  - Microbial diversity in two traditional bacterial douchi from Gansu province in
      northwest China using Illumina sequencing.
AB  - Douchi has been consumed as a flavoring ingredient for centuries. During
      production of douchi, numerous microorganisms play important roles in the
      hydrolysis and conversion of proteins and starch, which are related to the
      quality and flavor of the end product. Therefore, in the present study, the
      microbial diversity in two types of home-made traditional bacterial douchi from
      Gansu province in northwest China was studied by high-throughput sequencing, and
      a corresponding analysis of the bacterial and fungal communities were conducted.
      The results showed that geography may have impacted the fungal diversity and the
      bacterial and fungal species richness in the samples. The results also showed
      that the microbial community was significantly different in samples of different
      origin and the difference in the microbial community at the genus level was
      greater than at phylum level. Two dominant bacterial genera (Bacillus and
      Ignatzschineria) were common to the two samples, both of which had a relative
      abundance of more than 1%. Four bacterial genera (Staphylococcus, Aerococcus,
      Geobacillus, and Jeotgalicoccus) were dominant only in the sample from Qingyang,
      while another four (Carnobacterium, Proteus, Aneurinibacillus, and Enterococcus)
      were dominant only in the sample from Longnan. Two dominant fungal genera (Pichia
      and Candida) were shared by the two samples. Additionally, two genera
      (Rhodosporidium and Yarrowia) were dominant only in samples from Longnan. The
      functional genes of the bacteria present in samples indicated that a significant
      difference was observed in the bacterial community between samples of different
      origin. We also found that microbial interactions between bacterial and fungal
      communities in the samples were very complex. This study provides previously
      unknown information regarding the impact of the environment on microbial
      communities in douchi and lays a foundation for further investigations into food
      ecology in bacterial douchi.

PMID- 29570737
TI  - Implementing parallel spreadsheet models for health policy decisions: The impact
      of unintentional errors on model projections.
AB  - BACKGROUND: Spreadsheet software is increasingly used to implement systems
      science models informing health policy decisions, both in academia and in
      practice where technical capacity may be limited. However, spreadsheet models are
      prone to unintentional errors that may not always be identified using standard
      error-checking techniques. Our objective was to illustrate, through a
      methodologic case study analysis, the impact of unintentional errors on model
      projections by implementing parallel model versions. METHODS: We leveraged a real
      world need to revise an existing spreadsheet model designed to inform HIV policy.
      We developed three parallel versions of a previously validated spreadsheet-based
      model; versions differed by the spreadsheet cell-referencing approach (named
      single cells; column/row references; named matrices). For each version, we
      implemented three model revisions (re-entry into care; guideline-concordant
      treatment initiation; immediate treatment initiation). After standard error
      checking, we identified unintentional errors by comparing model output across the
      three versions. Concordant model output across all versions was considered error
      free. We calculated the impact of unintentional errors as the percentage
      difference in model projections between model versions with and without
      unintentional errors, using +/-5% difference to define a material error. RESULTS:
      We identified 58 original and 4,331 propagated unintentional errors across all
      model versions and revisions. Over 40% (24/58) of original unintentional errors
      occurred in the column/row reference model version; most (23/24) were due to
      incorrect cell references. Overall, >20% of model spreadsheet cells had material
      unintentional errors. When examining error impact along the HIV care continuum,
      the percentage difference between versions with and without unintentional errors
      ranged from +3% to +16% (named single cells), +26% to +76% (column/row
      reference), and 0% (named matrices). CONCLUSIONS: Standard error-checking
      techniques may not identify all errors in spreadsheet-based models. Comparing
      parallel model versions can aid in identifying unintentional errors and promoting
      reliable model projections, particularly when resources are limited.

PMID- 29570738
TI  - The author who wasn't there? Fairness and attribution in publications following
      access to population biobanks.
AB  - We conducted a document analysis that explored publication ethics and authorship
      in the context of population biobanks from both a theoretical (e.g. normative
      documents) and practical (e.g. biobank-specific documentation) perspective. The
      aim was to provide an overview of the state of authorship attribution in
      population biobanks and attempt to fill the gap in discussions around the issue.
      Our findings demonstrate that the most common approach adopted in both the
      normative and biobank-specific documentation is acknowledgment. A co-authorship
      approach was second and highlighted concerns surrounding the fairness of imposing
      authorship of the scientific leadership as a condition to access data and
      biosamples, as well as the alignment with the International Committee of Medical
      Journal Editors' criteria such as what is deemed a significant contribution and
      how to ensure accountability. Based on these findings, we propose a three-prong
      approach, that may be cumulative, to address the issue of authorship attribution
      in the context of population biobanks, namely 1) the biobank should be
      appropriately acknowledged; 2) an invitation for co-authorship should be made
      based on the spirit of collaboration and provided a substantial contribution has
      been made; and 3) a citation/referencing option should be available.

PMID- 29570739
TI  - Development of an improved RT-qPCR Assay for detection of Japanese encephalitis
      virus (JEV) RNA including a systematic review and comprehensive comparison with
      published methods.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is a major cause of encephalitis in
      Asia, and the commonest cause of mosquito-borne encephalitis worldwide. Detection
      of JEV RNA remains challenging due to the characteristic brief and low viraemia,
      with 0-25% of patients positive, and the mainstay of diagnosis remains detection
      of anti-JEV IgM antibody. METHODS: We performed a systematic review of published
      RT-PCR protocols, and evaluated them in silico and in vitro alongside new primers
      and probes designed using a multiple genome alignment of all JEV strains >9,000nt
      from GenBank, downloaded from the NCBI website (November 2016). The new assays
      included pan-genotype and genotype specific assays targeting genotypes 1 and 3.
      RESULTS: Ten RT-qPCR assays were compared, a pre-existing in-house assay, three
      published assays and six newly designed assays, using serial RNA dilutions. We
      selected three assays, one published and two novel assays, with the lowest limit
      of detection (LOD) for further optimisation and validation. One of the novel
      assays, detecting NS2A, showed the best results, with LOD approximately 4 copies/
      reaction, and no cross-reaction on testing closely related viruses in the JEV
      serocomplex, West Nile Virus and St. Louis Virus. The optimised assays were
      validated in consecutive patients with central nervous system infections admitted
      to hospitals in Laos, testing paired CSF and serum samples. CONCLUSIONS: We
      succeeded in developing a JEV specific RT-qPCR assay with at least 1 log10
      improved sensitivity as compared to existing assays. Further evaluation is
      required, field-testing the assay in a larger group of patients.

PMID- 29570740
TI  - Identifying bedrest using 24-h waist or wrist accelerometry in adults.
AB  - OBJECTIVES: To adapt and refine a previously-developed youth-specific algorithm
      to identify bedrest for use in adults. The algorithm is based on using an
      automated decision tree (DT) analysis of accelerometry data. DESIGN: Healthy
      adults (n = 141, 85 females, 19-69 years-old) wore accelerometers on the waist,
      with a subset also wearing accelerometers on the dominant wrist (n = 45).
      Participants spent ~24-h in a whole-room indirect calorimeter equipped with a
      force-platform floor to detect movement. METHODS: Minute-by-minute data from
      recordings of waist-worn or wrist-worn accelerometers were used to identify
      bedrest and wake periods. Participants were randomly allocated to development (n
      = 69 and 23) and validation (n = 72 and 22) groups for waist-worn and wrist-worn
      accelerometers, respectively. The optimized DT algorithm parameters were block
      length, threshold, bedrest-start trigger, and bedrest-end trigger. Differences
      between DT classification and synchronized objective classification by the room
      calorimeter to bedrest or wake were assessed for sensitivity, specificity, and
      accuracy using a Receiver Operating Characteristic (ROC) procedure applied to 1
      min epochs (n = 92,543 waist; n = 30,653 wrist). RESULTS: The optimal algorithm
      parameter values for block length were 60 and 45 min, thresholds 12.5 and 400
      counts/min, bedrest-start trigger 120 and 400 counts/min, and bedrest-end trigger
      1,200 and 1,500 counts/min, for the waist and wrist-worn accelerometers,
      respectively. Bedrest was identified correctly in the validation group with
      sensitivities of 0.819 and 0.912, specificities of 0.966 and 0.923, and
      accuracies of 0.755 and 0.859 by the waist and wrist-worn accelerometer,
      respectively. The DT algorithm identified bedrest/sleep with greater accuracy
      than a commonly used automated algorithm (Cole-Kripke) for wrist-worn
      accelerometers (p<0.001). CONCLUSIONS: The adapted DT accurately identifies
      bedrest in data from accelerometers worn by adults on either the wrist or waist.
      The automated bedrest/sleep detection DT algorithm for both youth and adults is
      openly accessible as a package "PhysActBedRest" for the R-computer language.

PMID- 29570741
TI  - Time- and depth-wise trophic niche shifts in Antarctic benthos.
AB  - Climate change is expected to affect resource-consumer interactions underlying
      stability in polar food webs. Polar benthic organisms have adapted to the marked
      seasonality characterising their habitats by concentrating foraging and
      reproductive activity in summer months, when inputs from sympagic and pelagic
      producers increase. While this enables the persistence of biodiverse food webs,
      the mechanisms underlying changes in resource use and nutrient transfer are
      poorly understood. Thus, our understanding of how temporal and spatial variations
      in the supply of resources may affect food web structure and functioning is
      limited. By means of C and N isotopic analyses of two key Antarctic benthic
      consumers (Adamussium colbecki, Bivalvia, and Sterechinus neumayeri, Echinoidea)
      and Bayesian mixing models, we describe changes in trophic niche and nutrient
      transfer across trophic levels associated with the long- and short-term diet and
      body size of specimens sampled in midsummer in both shallow and deep waters.
      Samplings occurred soon after the sea-ice broke up at Tethys Bay, an area
      characterised by extreme seasonality in sea-ice coverage and productivity in the
      Ross Sea. In the long term, the trophic niche was broader and variation between
      specimens was greater, with intermediate-size specimens generally consuming a
      higher number of resources than small and large specimens. The coupling of energy
      channels in the food web was consequently more direct than in the short term.
      Sediment and benthic algae were more frequently consumed in the long term, before
      the sea-ice broke up, while consumers specialised on sympagic algae and plankton
      in the short term. Regardless of the time scale, sympagic algae were more
      frequently consumed in shallow waters, while plankton was more frequently
      consumed in deep waters. Our results suggest a strong temporal relationship
      between resource availability and the trophic niche of benthic consumers in
      Antarctica. Potential climate-driven changes in the timing and quality of
      nutrient inputs may have profound implications for the structure of polar food
      webs and the persistence of their constituent species, which have adapted their
      trophic niches to a highly predictable schedule of resource inputs.

PMID- 29570744
TI  - Identification of a robust subpathway-based signature for acute myeloid leukemia
      prognosis using an miRNA integrated strategy.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease, and survival signatures
      are urgently needed to better monitor treatment. MiRNAs displayed vital
      regulatory roles on target genes, which was necessary involved in the complex
      disease. We therefore examined the expression levels of miRNAs and genes to
      identify robust signatures for survival benefit analyses. First, we reconstructed
      subpathway graphs by embedding miRNA components that were derived from low
      throughput miRNA-gene interactions. Then, we randomly divided the data sets from
      The Cancer Genome Atlas (TCGA) into training and testing sets, and further formed
      100 subsets based on the training set. Using each subset, we identified survival
      related miRNAs and genes, and identified survival subpathways based on the
      reconstructed subpathway graphs. After statistical analyses of these survival
      subpathways, the most robust subpathways with the top three ranks were
      identified, and risk scores were calculated based on these robust subpathways for
      AML patient prognoses. Among these robust subpathways, three representative
      subpathways, path: 05200_10 from Pathways in cancer, path: 04110_20 from Cell
      cycle, and path: 04510_8 from Focal adhesion, were significantly associated with
      patient survival in the TCGA training and testing sets based on subpathway risk
      scores. In conclusion, we performed integrated analyses of miRNAs and genes to
      identify robust prognostic subpathways, and calculated subpathway risk scores to
      characterize AML patient survival.

PMID- 29570742
TI  - Impact of acute-phase complications and interventions on 6-month survival after
      stroke. A prospective observational study.
AB  - The outcome of stroke patients is complex and multidimensional. We evaluated the
      impact of acute-phase variables, including clinical state, complications,
      resource use and interventions, on 6-month survival after first-ever stroke,
      taking into account baseline conditions exerting a possible effect on outcome. As
      part of a National Research Program, we performed a prospective observational
      study of acute stroke patients in four Italian Regions. Consecutive patients
      admitted for a period of 3 months to the emergency rooms of participating
      hospitals were included. A total of 1030 patients were enrolled (median age 76.0
      years, 52.1% males). At 6 months, 816 (79.2%) were alive, and 164 (15.9%)
      deceased. Survival status at the 6-month follow-up was missing for 50 (4.9%).
      Neurological state in the acute phase was significantly worse in patients
      deceased at 6 months, who showed also higher frequency of acute-phase
      complications. Cox regression analysis adjusted for demographics, pre-stroke
      function, baseline diseases and risk factors, indicated as significant predictors
      of 6-month death altered consciousness (HR, 1.70; 95% CI, 1.14-2.53), total
      anterior circulation infarct (HR, 2.13; 95% CI, 1.44-3.15), hyperthermia (HR,
      1.70; 95% CI, 1.18-2.45), pneumonia (HR, 1.76; 95% CI, 1.18-2.61), heart failure
      (HR, 2.87; 95% CI, 1.34-6.13) and nasogastric feeding (HR, 2.35; 95% CI, 1.53
      3.60), while antiplatelet therapy during acute phase (HR, 0.56; 95% CI, 0.39
      0.79), and early mobilisation (HR, 0.55; 95% CI, 0.36-0.84) significantly
      increased 6-month survival. In a prospective observational study, stroke severity
      and some acute-phase complications, potentially modifiable, significantly
      increased the risk of 6-month death, independently of baseline variables. Early
      mobilisation positively affected survival, highlighting the role of early
      rehabilitation after stroke.

PMID- 29570743
TI  - Novel putative drivers revealed by targeted exome sequencing of advanced solid
      tumors.
AB  - Next generation sequencing (NGS) is becoming increasingly integrated into
      oncological practice and clinical research. NGS methods have also provided
      evidence for clonal evolution of cancers during disease progression and
      treatment. The number of variants associated with response to specific
      therapeutic agents keeps increasing. However, the identification of novel driver
      mutations as opposed to passenger (phenotypically silent or clinically
      irrelevant) mutations remains a major challenge. We conducted targeted exome
      sequencing of advanced solid tumors from 44 pre-treated patients with solid
      tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors,
      sarcomas and others. We catalogued established driver mutations and putative new
      drivers as predicted by two distinct algorithms. The established drivers we
      detected were consistent with published observations. However, we also detected a
      significant number of mutations with driver potential never described before in
      each tumor type we studied. These putative drivers belong to key cell fate
      regulatory networks, including potentially druggable pathways. Should our
      observations be confirmed, they would support the hypothesis that new driver
      mutations are selected by treatment in clinically aggressive tumors, and indicate
      a need for longitudinal genomic testing of solid tumors to inform second line
      cancer treatment.

PMID- 29570745
TI  - A genome-wide identification and comparative analysis of the lentil MLO genes.
AB  - Powdery mildew is a widespread fungal plant disease that can cause significant
      losses in many crops. Some MLO genes (Mildew resistance locus O) have proved to
      confer a durable resistance to powdery mildew in several species. Resistance
      granted by the MLO gene family members has prompted an increasing interest in
      characterizing these genes and implementing their use in plant breeding. Lentil
      (Lens culinaris Medik.) is a widely grown food legume almost exclusively consumed
      as dry seed with an average world production of 4.5 million tons. Powdery mildew
      causes severe losses on certain lentil cultivars under particular environmental
      conditions. Data mining of the lentil CDC Redberry draft genome allowed to
      identify up to 15 gene sequences with homology to known MLO genes, designated as
      LcMLOs. Further characterization of these gene sequences and their deduced
      protein sequences demonstrated conformity with key MLO protein characteristics
      such as the presence of transmembrane and calmodulin binding domains, as well as
      that of other conserved motifs. Phylogenetic and other comparative analyses
      revealed that LcMLO1 and LcMLO3 are the most likely gene orthologs related to
      powdery mildew response in other species, sharing a high similarity with other
      known resistance genes of dicot species, such as pea PsMLO1 and Medicago
      truncatula MtMLO1 and MtMLO3. Sets of primers were designed as tools to PCR
      amplify the genomic sequences of LcMLO1 and LcMLO3, also to screen lentil
      germplasm in search of resistance mutants. Primers were used to obtain the
      complete sequences of these two genes in all of the six wild lentil relatives.
      Respective to each gene, all Lens sequences shared a high similarity. Likewise,
      we used these primers to screen a working collection of 58 cultivated and 23 wild
      lentil accessions in search of length polymorphisms present in these two genes.
      All these data widen the insights on this gene family and can be useful for
      breeding programs in lentil and close related species.

PMID- 29570746
TI  - The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus
      serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named
      endemic lineage.
AB  - Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many
      times in the past. Despite its seriousness, limited attempts have been made to
      understand the disease to ameliorate its effects-current recommendation for
      vaccines being based solely on immunological assessments rather than on molecular
      identification. The general belief is that the cattle population in Sri Lanka
      acquired the FMD virus (FMDV) strains via introductions from India. However,
      there could be endemic FMDV lineages circulating in Sri Lanka. To infer the
      phylogenetic relationships of the FMDV strains in the island, we sequenced the
      VP1 genomic region of the virus isolates collected during the 2014 outbreak
      together with a few reported cases in 2012 and 1997 and compared them to VP1
      sequences from South Asia. The FMDV strains collected in the 2014 outbreak
      belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected
      in 2012 and 1997 belonged to another lineage called 'unnamed' by the World
      Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present
      analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to
      Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were
      estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively,
      suggesting that Srl-97 evolves slowly.

PMID- 29570747
TI  - Dogs (Canis familiaris) stick to what they have learned rather than conform to
      their conspecifics' behavior.
AB  - In recent years, an increasing number of studies has investigated majority
      influence in nonhuman animals. However, due to both terminological and
      methodological issues, evidence for conformity in nonhuman animals is scarce and
      controversial. Preliminary evidence suggests that wild birds, wild monkeys, and
      fish show conformity, that is, forgoing personal information in order to copy the
      majority. By contrast, chimpanzees seem to lack this tendency. The present study
      is the first to examine whether dogs (Canis familiaris) show conformity.
      Specifically, we tested whether dogs conform to a majority of conspecifics rather
      than stick to what they have previously learned. After dogs had acquired a
      behavioral preference via training (i.e., shaping), they were confronted with
      counter-preferential behavior of either no, one or three conspecifics.
      Traditional frequentist analyses show that the dogs' behavior did not differ
      significantly between the three conditions. Complementary Bayesian analyses
      suggest that our data provide moderate evidence for the null hypothesis. In
      conclusion, our results suggest that dogs stick to what they have learned rather
      than conform to the counter-preferential behavior of others. We discuss the
      possible statistical and methodological limitations of this finding. Furthermore,
      we take a functional perspective on conformity and discuss under which
      circumstances dogs might show conformity after all.

PMID- 29570748
TI  - Inertial Properties of Football Helmets.
AB  - The inertial properties of a helmet play an important role in both athletic
      performance and head protection. In this study, we measured the inertial
      properties of 37 football helmets, a National Operating Committee on Standards
      for Athletic Equipment (NOCSAE) size 71/4 headform, and a 50th percentile male
      Hybrid III dummy head. The helmet measurements were taken with the helmets placed
      on the Hybrid III dummy head. The center of gravity and moment of inertia were
      measured about six axes (x, y, z, xy, yz, and xz), allowing for a complete
      description of the inertial properties of the head and helmets. Total helmet mass
      averaged 1834+/-231 g, split between the shell (1377+/-200 g) and the facemask
      (457+/-101 g). On average, the football helmets weighed 41+/-5% as much as the
      Hybrid III dummy head. The center of gravity of the helmeted head was 1.1+/-3.0
      mm anterior and 10.3+/-1.9 mm superior to the center of gravity of the bare head.
      The moment of inertia of the helmeted head was approximately 2.2+/-0.2 times
      greater than the bare head about all axes.

PMID- 29570749
TI  - Influence of the musculotendon dynamics on the muscle force sharing problem of
      the shoulder ? a fully inverse dynamics approach.
AB  - Most dynamic simulations are based on inverse dynamics, being the time-dependent
      physiological nature of the muscle properties rarely considered due to numerical
      challenges. Since the influence of muscle physiology on the consistency of
      inverse dynamics simulations remains unclear, the purpose of the present study is
      to evaluate the computational efficiency and biological validity of four
      musculotendon models that differ in the simulation of the muscle activation and
      contraction dynamics. Inverse dynamic analyses are performed using a spatial
      musculoskeletal model of the upper limb. The muscle force sharing problem is
      solved for 5 repetitions of unloaded and loaded motions of shoulder abduction and
      shoulder flexion. The performance of the musculotendon models is evaluated by
      comparing muscle activation predictions with EMG signals, measured synchronously
      with motion for 11 muscles, and the glenohumeral joint reaction forces estimated
      numerically with those measured in vivo. The results show similar muscle
      activations for all muscle models. Overall, high cross-correlations are computed
      between muscle activations and the EMG signals measured for all movements
      analyzed, which provides confidence in the results. The glenohumeral joint
      reaction forces estimated compare well with those measured in vivo, but the
      influence of the muscle dynamics is found to be negligible. In conclusion, for
      slow-speed, standard movements of the upper limb, as those studied here, the
      activation and musculotendon contraction dynamics can be neglected in inverse
      dynamic analyses without compromising the prediction of muscle and joint reaction
      forces.

PMID- 29570750
TI  - Trends in Obesity and Severe Obesity Prevalence in US Youth and Adults by Sex and
      Age, 2007-2008 to 2015-2016.

PMID- 29570751
TI  - Applying a Hybrid Experimental-Computational Technique to Study Elbow Joint
      Ligamentous Stabilizers.
AB  - Much of our understanding of the role of elbow ligaments to overall joint
      biomechanics has been developed through in vitro cadaver studies using joint
      motion simulators. The principle of superposition can be used to indirectly
      compute the force contributions of ligaments during prescribed motions. Previous
      studies have analyzed the contribution of different soft tissue structures to the
      stability of human elbow joints, but have limitations in evaluating the loads
      sustained by those tissues. This manuscript introduces a unique, hybrid
      experimental-computational technique for measuring and simulating the
      biomechanical contributions of ligaments to elbow joint kinematics and stability.
      In vitro testing of cadaveric joints is enhanced by the incorporation of fully
      parametric virtual ligaments, which are used in place of the native joint
      stabilizers to characterize the contribution of elbow ligaments during simple
      flexion-extension motions using the principle of superposition. Our results
      support previously reported findings that the anterior medial collateral ligament
      and the radial collateral ligament are the primary soft tissue stabilizers for
      the elbow joint. Tuned virtual ligaments employed in this study were able to
      restore the kinematics and laxity of elbows to within 2 degrees  of native joint
      behavior. The hybrid framework presented in this study demonstrates promising
      capabilities in measuring the biomechanical contribution of ligamentous
      structures to joint stability.

PMID- 29570753
TI  - The Relationship Between Speech, Language, and Phonological Awareness in
      Preschool-Age Children With Developmental Disabilities.
AB  - Purpose: A number of intrinsic factors, including expressive speech skills, have
      been suggested to place children with developmental disabilities at risk for
      limited development of reading skills. This study examines the relationship
      between these factors, speech ability, and children's phonological awareness
      skills. Method: A nonexperimental study design was used to examine the
      relationship between intrinsic skills of speech, language, print, and letter
      sound knowledge to phonological awareness in 42 children with developmental
      disabilities between the ages of 48 and 69 months. Hierarchical multiple
      regression was done to determine if speech ability accounted for a unique amount
      of variance in phonological awareness skill beyond what would be expected by
      developmental skills inclusive of receptive language and print and letter-sound
      knowledge. Results: A range of skill in all areas of direct assessment was found.
      Children with limited speech were found to have emerging skills in print
      knowledge, letter-sound knowledge, and phonological awareness. Speech ability did
      not predict a significant amount of variance in phonological awareness beyond
      what would be expected by developmental skills of receptive language and print
      and letter-sound knowledge. Conclusion: Children with limited speech ability were
      found to have receptive language and letter-sound knowledge that supported the
      development of phonological awareness skills. This study provides implications
      for practitioners and researchers concerning the factors related to early reading
      development in children with limited speech ability and developmental
      disabilities.

PMID- 29570752
TI  - Selecting Sensitive Parameter Subsets in Dynamical Models With Application to
      Biomechanical System Identification.
AB  - Estimating many parameters of biomechanical systems with limited data may achieve
      good fit but may also increase 95% confidence intervals in parameter estimates.
      This results in poor identifiability in the estimation problem. Therefore, we
      propose a novel method to select sensitive biomechanical model parameters that
      should be estimated, while fixing the remaining parameters to values obtained
      from preliminary estimation. Our method relies on identifying the parameters to
      which the measurement output is most sensitive. The proposed method is based on
      the Fisher information matrix (FIM). It was compared against the nonlinear least
      absolute shrinkage and selection operator (LASSO) method to guide modelers on the
      pros and cons of our FIM method. We present an application identifying a
      biomechanical parametric model of a head position-tracking task for ten human
      subjects. Using measured data, our method (1) reduced model complexity by only
      requiring five out of twelve parameters to be estimated, (2) significantly
      reduced parameter 95% confidence intervals by up to 89% of the original
      confidence interval, (3) maintained goodness of fit measured by variance
      accounted for (VAF) at 82%, (4) reduced computation time, where our FIM method
      was 164 times faster than the LASSO method, and (5) selected similar sensitive
      parameters to the LASSO method, where three out of five selected sensitive
      parameters were shared by FIM and LASSO methods.

PMID- 29570754
TI  - Computational Fluid Dynamics of Vascular Disease in Animal Models.
AB  - Recent applications of computational fluid dynamics (CFD) applied to the
      cardiovascular system have demonstrated its power in investigating the impact of
      hemodynamics on disease initiation, progression, and treatment outcomes. Flow
      metrics such as pressure distributions, wall shear stresses (WSS), and blood
      velocity profiles can be quantified to provide insight into observed pathologies,
      assist with surgical planning, or even predict disease progression. While
      numerous studies have performed simulations on clinical human patient data, it
      often lacks prediagnosis information and can be subject to large intersubject
      variability, limiting the generalizability of findings. Thus, animal models are
      often used to identify and manipulate specific factors contributing to vascular
      disease because they provide a more controlled environment. In this review, we
      explore the use of CFD in animal models in recent studies to investigate the
      initiating mechanisms, progression, and intervention effects of various vascular
      diseases. The first section provides a brief overview of the CFD theory and tools
      that are commonly used to study blood flow. The following sections are separated
      by anatomical region, with the abdominal, thoracic, and cerebral areas
      specifically highlighted. We discuss the associated benefits and obstacles to
      performing CFD modeling in each location. Finally, we highlight animal CFD
      studies focusing on common surgical treatments, including arteriovenous fistulas
      (AVF) and pulmonary artery grafts. The studies included in this review
      demonstrate the value of combining CFD with animal imaging and should encourage
      further research to optimize and expand upon these techniques for the study of
      vascular disease.

PMID- 29570755
TI  - The Second Amendment and a Well-Regulated Firearms Environment.

PMID- 29570756
TI  - Appropriate Objective Functions for Quantifying Iris Mechanical Properties Using
      Inverse Finite Element Modeling.
AB  - Quantifying the mechanical properties of the iris is important, as it provides
      insight into the pathophysiology of glaucoma. Recent ex vivo studies have shown
      that the mechanical properties of the iris are different in glaucomatous eyes as
      compared to normal ones. Notwithstanding the importance of the ex vivo studies,
      such measurements are severely limited for diagnosis and preclude development of
      treatment strategies. With the advent of detailed imaging modalities, it is
      possible to determine the in vivo mechanical properties using inverse finite
      element (FE) modeling. An inverse modeling approach requires an appropriate
      objective function for reliable estimation of parameters. In the case of the
      iris, numerous measurements such as iris chord length (CL) and iris concavity
      (CV) are made routinely in clinical practice. In this study, we have evaluated
      five different objective functions chosen based on the iris biometrics (in the
      presence and absence of clinical measurement errors) to determine the appropriate
      criterion for inverse modeling. Our results showed that in the absence of
      experimental measurement error, a combination of iris CL and CV can be used as
      the objective function. However, with the addition of measurement errors, the
      objective functions that employ a large number of local displacement values
      provide more reliable outcomes.

PMID- 29570757
TI  - Simulation of Airflow in an Idealized Emphysematous Human Acinus.
AB  - Emphysema is the permanent enlargement of air spaces in the respiratory regions
      of the lung due to destruction of the inter-alveolar septa. The progressive
      coalescence of alveoli and alveolar ducts into larger airspaces leads to the
      disruption of normal airway wall motion and airflow rates within the pulmonary
      acinus. To contribute to the understanding of the individual effects of emphysema
      during its earliest stages, computational fluid dynamics simulations of airflow
      in mathematically-derived models of the pulmonary acinus were performed. The here
      generated computational domain consists of two generations of alveolar ducts
      within the pulmonary acinus, with alveolar geometries approximated as closely
      packed, fourteen-sided polygons. Physiologically realistic airflow rates and wall
      motions were used to study airflow patterns within subsequent generations of
      alveolar ducts during the inspiratory and expiratory phases of the breathing
      cycle. The effects of progressive emphysema on the airway wall motion and flow
      rates were simulated by sequentially removing all alveolar septa within each
      alveolar duct. Parametric studies were presented to independently assess the
      relative influence of progressive septal destruction of airway motion and flow
      rates. The results illustrate that septal destruction lowers the flow resistance
      through the alveolar ducts but has little influence on the mass transport of
      oxygen into the alveoli. Septal destruction has a net effect on the flow field by
      favoring the development of recirculatory flow patterns in individual alveoli.

PMID- 29570758
TI  - Benchmark for Numerical Models of Stented Coronary Bifurcation Flow.
AB  - In-stent restenosis ails many patients who have undergone stenting. When the
      stented artery is a bifurcation, the intervention is particularly critical
      because of the complex stent geometry involved in these structures. Computational
      fluid dynamics (CFD) has been shown to be an effective approach when modeling
      blood flow behavior and understanding the mechanisms that underlie in-stent
      restenosis. However, these CFD models require validation through experimental
      data in order to be reliable. It is with this purpose in mind that we performed
      particle image velocimetry (PIV) measurements of velocity fields within flows
      through a simplified coronary bifurcation. Although the flow in this simplified
      bifurcation differs from the actual blood flow, it emulates the main fluid
      dynamic mechanisms found in hemodynamic flow. Experimental measurements were
      performed for several stenting techniques in both steady and unsteady flow
      conditions. The test conditions were strictly controlled, and uncertainty was
      accurately predicted. The results obtained in this research represent readily
      accessible, easy to emulate, detailed velocity fields and geometry, and they have
      been successfully used to validate our numerical model. These data can be used as
      a benchmark for further development of numerical CFD modeling in terms of
      comparison of the main flow pattern characteristics.

PMID- 29570759
TI  - Using Ceramic-on-Ceramic Bearings in Total Hip Arthroplasty Necessitating 44- or
      46-mm Metal Shells.
AB  - Ceramic-on-ceramic articulation shows the lowest wear, with a low incidence of
      osteolysis. A small cup limits options regarding liner thickness and femoral
      implant size. The purpose of this study was to evaluate the safety of a 4-mm
      thick ceramic liner and the outcomes of cementless total hip arthroplasty using a
      44- or 46-mm metal shell and a ceramic-on-ceramic bearing at mid- to long-term
      follow-up. Between May 2003 and June 2008, 80 patients (88 hips) who had hip
      osteoarthritis and a hypoplastic acetabulum underwent cementless total hip
      arthroplasty using a 44- or 46-mm metal shell and a ceramic-on-ceramic bearing.
      Sixty-eight of these patients (76 hips) were followed for an average of 8 years.
      The ceramic-related complications, clinical and radiological results, and Kaplan
      Meier survivorship of these patients were evaluated. Mean Harris hip score had
      improved to 88 points (range, 49-100 points) at final follow-up. No ceramic
      fractures occurred during follow-up. All acetabular and femoral prostheses had
      bone ingrowth, and there was no measurable wear in any hip. In 1 patient, a
      radiolucent lesion occurred around the acetabular cup. Two hips underwent
      revision because of periprosthetic fractures. The survival rates of the
      acetabular cups and the femoral stems were 100% and 97.4%, respectively. The thin
      (4 mm) ceramic liner did not increase the risk of ceramic fracture and did not
      affect the mid- to long-term results and survival of cementless total hip
      arthroplasty using 44- or 46-mm metal shells. [Orthopedics. 2018; 41(3):e354
      e359.].

PMID- 29570760
TI  - The Role of Aspirin and Unfractionated Heparin Combination Therapy Immediately
      After Total Hip and Knee Arthroplasty.
AB  - Aspirin and unfractionated heparin (UH) are accepted options for venous
      thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA). The use
      of aspirin in addition to UH in preventing VTE after TJA has yet to be studied.
      The primary objective of this study was to determine VTE rates in patients
      receiving aspirin monotherapy and those receiving aspirin and UH combination
      therapy immediately following TJA. A TJA database from a single hospital system
      was retrospectively reviewed to identify all patients who underwent primary hip
      or knee arthroplasty from 2013 to 2016. Patients were divided into 3 groups based
      on postoperative VTE chemoprophylaxis: aspirin only, aspirin with 1 dose of UH,
      and aspirin with multiple doses of UH. There were 5350 patients included: 1024
      aspirin only, 1695 aspirin plus 1 dose of UH, and 2631 aspirin plus multiple
      doses of UH. Deep venous thrombosis and pulmonary embolus rates did not vary
      significantly between groups (deep venous thrombosis: 1.1%, 0.9%, and 1.2%,
      respectively, P=.701; pulmonary embolus: 0.3%, 0.3%, and 0.2%, respectively,
      P=.894). Transfusion rates were significantly greater with 1 dose of UH (1.8%)
      and multiple doses of UH (4.3%) compared with aspirin only (0.9%) (P<.001).
      Additionally, the postoperative hemoglobin decreased significantly more
      postoperatively with the use of UH (P<.001). Aspirin and UH combination therapy
      did not decrease VTE incidence compared with aspirin monotherapy. Additionally,
      there was greater perioperative blood loss and an increased rate of blood
      transfusion in patients receiving UH. On the basis of these findings, the authors
      do not recommend UH as an additional mode of VTE prophylaxis when prescribing
      aspirin after elective TJA. [Orthopedics. 2018; 41(3):171-176.].

PMID- 29570761
TI  - Treatment of Lateral Tibial Condylar Fractures Using Bioactive, Bioresorbable
      Forged Composites of Raw Particulate Unsintered Hydroxyapatite/Poly-L-Lactide
      Screws.
AB  - Forged composites of raw particulate unsintered hydroxyapatite/poly-L-lactide (F
      u-HA/PLLA) devices possess high mechanical strength, bioactivity, and radio
      opacity. The aim of this study was to assess the efficacy of F-u-HA/PLLA screws
      in the treatment of lateral tibial condylar fractures. From January 2005 to
      December 2010, a total of 7 patients with displaced closed lateral tibial
      condylar fractures (Schatzker type II) were treated using F-u-HA/PLLA screws.
      Open reduction and internal fixation was performed using 2 or 3 F-u-HA/PLLA
      screws. After surgery, weight bearing was not allowed for 6 weeks. Range of
      motion exercise was initiated after removal of the plaster splint. Radiographs
      were evaluated for fracture healing, joint depression, and the radioopacity of F
      u-HA/PLLA screws. Clinical outcomes and postoperative complications were also
      assessed. Average follow-up was 44 months. All fractures were successfully
      healed. Average values for joint depression were 4.7 mm (range, 2-9 mm)
      preoperatively, 0.4 mm (range, 0-1 mm) postoperatively, and 0.4 mm (range, 0-1
      mm) at final follow-up. Whole shadows of F-u-HA/PLLA screws were observed during
      the follow-up period. Breakage of screws, osteolysis, and a radiolucent zone
      around the screws were not observed at final follow-up. Average knee flexion and
      extension were 134 degrees  (range, 110 degrees  to 150 degrees ) and -1 degrees 
      (range, -10 degrees  to 0 degrees ), respectively. No patient had wound
      infection, late aseptic tissue response, or foreign body reaction
      postoperatively. None of the patients reported pain at final follow-up. These
      results suggest that F-u-HA/PLLA screws could be an alternative option for the
      treatment of lateral tibial condylar fractures. [Orthopedics. 2018; 41(3):e365
      e368.].

PMID- 29570762
TI  - The Proximal and Distal Femoral Canal Geometry Influences Cementless Stem
      Anchorage and Revision Hip and Knee Implant Stability.
AB  - Although cementless revision arthroplasty of the hip has become the gold
      standard, revision arthroplasty of the distal femur is controversial. This study
      evaluated the anchoring principles of different femoral revision stem designs in
      extended bone defect situations, taking into account the anatomical conditions of
      the proximal and distal femur, and the resulting primary stability. Cementless
      press-fit stems of 4 different designs were implanted in synthetic femurs. The
      specimens were analyzed by computed tomography and were tested considering
      axial/torsional stiffness and migration resistance. Different stem designs
      anchored in different femoral canal geometries achieved comparable primary
      stability. Despite considerably different anchorage lengths, no difference in
      migration behavior or stiffness was found. Both in the distal femur and in the
      proximal femur, the conical stems showed a combination of conical and 3-point
      anchorage. Regarding the cylindrical stem tested, a much shorter anchorage length
      was sufficient in the distal femur to achieve comparable primary stability. In
      the investigated osseous defect model, the stem design (conical vs cylindrical),
      not the geometry of the femoral canal (proximal vs distal), was decisive
      regarding the circumferential anchorage length. For the conical stems, it can be
      postulated that there are reserves available for achieving a conical-circular
      fixation as a result of the large contact length. For the cylindrical stems, only
      a small reserve for a stable anchorage can be assumed. [Orthopedics. 2018;
      41(3):e369-e375.].

PMID- 29570763
TI  - Trends and Risk Factors for 1-Year Revision of the Latarjet Procedure: The New
      York State Experience During the Past Decade.
AB  - Little research has been conducted evaluating surgical trends during the past 10
      years and subsequent procedure risk factors for patients undergoing bone-blocking
      procedures for the treatment of anterior shoulder instability. The Statewide
      Planning and Research Cooperative System database was queried between 2003 and
      2014 to identify patients undergoing soft tissue or bone-blocking procedures for
      anterior shoulder instability in New York. Patient demographics and 1-year
      subsequent procedures were analyzed. Multivariate logistic regression analyses
      were conducted to identify 1-year subsequent procedure risk factors. From 2003
      through 2014, a total of 540 patients had Latarjet procedures performed. During
      this period, the volume of Latarjet procedures increased by 950%, from 12
      procedures in 2003 to 126 procedures in 2014. The volume of open Bankart repairs
      declined by 77%; arthroscopic Bankart repairs fluctuated, being up (328%) between
      2003 and 2012 and then down (6%) between 2012 and 2014. Of the 540 patients, 2.4%
      (13 of 540) required intervention for recurrent shoulder instability events. Age
      older than 20 years and workers' compensation were identified as independent risk
      factors for reoperation. The number of bone-blocking procedures, such as the
      Latarjet, has increased by nearly 1000% during the past decade in New York. Only
      2.4% (13 of 540) of the patients had subsequent shoulder instability
      interventions. [Orthopedics. 2018; 41(3):e389-e394.].

PMID- 29570764
TI  - Atypical Mycobacterial Infections of the Upper Extremity.
AB  - Atypical mycobacterial infections of upper extremity synovial-lined structures
      are often misdiagnosed and unrecognized. Despite an increasing incidence, lack of
      physician awareness of these pathogens may result in considerable delay in
      diagnosis and management, potentially leading to permanent disability. The
      authors conducted a literature review and analyzed 31 cases of penetrating
      atypical mycobacterial infection to better understand the clinical
      characteristics and to evaluate their posttreatment complication rate compared
      with available literature. Medical records for culture-positive cases of
      tenosynovial or intra-articular atypical mycobacterial infections of the upper
      extremity that were treated were retrospectively reviewed. Treatment outcomes
      were analyzed against published case reviews and case series. Thirty-one cases of
      penetrating atypical mycobacterial infection were identified. Mycobacterium
      marinum (n=11) was the most common organism and was associated with aquatic
      exposure. Twenty-eight cases received empiric treatment, 17 of which received
      contraindicated treatment. Patients saw an average of 5 physicians prior to
      receiving an accurate diagnosis, and the mean time to diagnosis was 10 months.
      All cases received antibiotic treatment in addition to surgical management.
      Twenty cases (68%) failed treatment outcomes. Delay in diagnosis and
      inappropriate management of atypical mycobacterial infections may lead to a
      treatment failure rate that is higher than what has been reported in the
      literature. Mycobacterium avium and M fortuitum had significantly higher failure
      rates than other organisms. A high index of suspicion is required to make a
      diagnosis and prevent residual disability. [Orthopedics. 2018; 41(3):e383-e388.].

PMID- 29570765
TI  - Effect of Bisphosphonate Pretreatment on Fresh Osteochondral Allografts: Analysis
      of In Vitro Graft Structure and In Vivo Osseous Incorporation.
AB  - Fresh allograft transplantation of osteochondral defects restores functional
      articular cartilage and subchondral bone; however, rapid loss of chondrocyte
      viability during storage and osteoclast-mediated bone resorption at the graft
      host interface after transplantation negatively impact outcomes. The authors
      present a pilot study evaluating the in vitro and in vivo impact of augmenting
      storage media with bisphosphonates. Forty cylindrical osteochondral cores were
      harvested from femoral condyles of human cadaveric specimens and immersed in
      either standard storage media or storage media supplemented with nitrogenated or
      non-nitrogenated bisphosphonates. Maintenance of graft structure and chondrocyte
      viability were assessed at 3 time points. A miniature swine trochlear defect
      model was used to evaluate the influence of bisphosphonate-augmented storage
      media on in vivo incorporation of fresh osteochondral tissue, which was
      quantified via MUCT and decalcified histology. In the in vitro study, Safranin
      O/Fast Green staining showed that both low- and high-dose nitrogenated-treated
      grafts retained chondrocyte viability and cartilage matrix for up to 43 days of
      storage. Allografts stored in nitrogenated-augmented storage media showed both
      MUCT and histologic evidence of enhanced in vivo bony and cartilaginous
      incorporation in the miniature swine trochlear defect model. Several preclinical
      studies have shown the potential for enhanced storage of fresh osteochondral
      allografts via additions of relatively common drugs and biomolecules. This study
      showed that supplementing standard storage media with nitrogenated
      bisphosphonates may improve maintenance of chondrocyte viability and graft
      structure during cold storage as well as enhance in vivo osseous and
      cartilaginous incorporation of the graft. [Orthopedics: 2018; 41(3):e376-e382.].

PMID- 29570766
TI  - Arthroscopic Repair of Chronic Tears of the Anterior Horn of the Lateral Meniscus
      That Includes Covering the Lesion With an Infrapatellar Pedicle Fat Flap.
AB  - This study analyzed the efficacy and safety of arthroscopic outside-in repair of
      the anterior horn of the lateral meniscus that includes covering the lesion with
      an infrapatellar pedicle fat flap in patients with chronic tears. This
      retrospective study reviewed 87 patients with chronic tears of the anterior horn
      of the lateral meniscus who underwent arthroscopic outside-in repair, which
      included covering the lesion with an infrapatellar pedicle fat flap (group A,
      n=45) or not (group B, n=42). The 2 groups were similar in terms of age, sex,
      body mass index, and disease duration. Patient results were assessed with Tegner,
      Lysholm, and visual analog scale scores; healing criteria; magnetic resonance
      imaging; and complication rates. Mean follow-up was 38.2 months. Tegner and
      Lysholm scores improved postoperatively in both groups (all P<.01) and were
      similar for the 2 groups (all P>.05). Visual analog scale scores were reduced
      postoperatively in both groups (P<.01) and similar for the 2 groups (P>.05).
      Healing rates and complication rates did not differ between the 2 groups (all
      P>.05), but healing on magnetic resonance imaging was better in group A than
      group B (P<.05). The repair of chronic tears of the anterior horn of the lateral
      meniscus can lead to good clinical outcomes and a satisfactory success rate.
      Covering the repair site with an infrapatellar pedicle fat flap may improve
      meniscal healing and does not increase the complication rate. [Orthopedics. 2018;
      41(3):e360-e364.].

PMID- 29570767
TI  - Thermodynamics of the pseudo-knot in helix 18 of 16S ribosomal RNA.
AB  - A fragment of E. coli 16S rRNA formed by nucleotides 500 to 545 is termed helix
      18. Nucleotides 505-507 and 524-526 form a pseudo-knot and its distortion affects
      ribosome function. Helix 18 isolated from the ribosome context is thus an
      interesting fragment to investigate the structural properties and folding of RNA
      with pseudo-knots. With all-atom molecular dynamics simulations, spectroscopic
      and gel electrophoresis experiments, we investigated thermodynamics of helix 18,
      with a focus on its pseudo-knot. In solution studies at ambient conditions we
      observed dimerization of helix 18. We proposed that the loop, containing
      nucleotides forming the pseudo-knot, interacts with another monomer of helix 18.
      The native dimer is difficult to break but introducing mutations in the pseudo
      knot indeed assured a monomeric form of helix 18. Molecular dynamics simulations
      at 310 K confirmed the stability of the pseudo-knot but at elevated temperatures
      this pseudo-knot was the first part of helix 18 to lose the hydrogen bond
      pattern. To further determine helix 18 stability, we analyzed the interactions of
      helix 18 with short oligomers complementary to a nucleotide stretch containing
      the pseudo-knot. The formation of higher-order structures by helix 18 impacts
      hybridization efficiency of peptide nucleic acid and 2'-O methyl RNA oligomers.

PMID- 29570769
TI  - Low hair cortisol concentration and emerging attention-deficit/hyperactivity
      symptoms in preschool age.
AB  - Previous research demonstrated hypoactivity of the HPA axis in children with
      attention-deficit/hyperactivity disorder (ADHD) or externalizing symptoms. We
      analyzed the predictive association between the long-term HPA axis activity and
      increasing symptoms of ADHD in the preschool period. The sample consisted of n =
      125 4-year-old children and their families (including n = 64 children with
      elevated ADHD symptoms). ADHD symptoms were assessed by a structured clinical
      interview with the mother and by parent- and teacher-report questionnaires. The
      long-term HPA axis activity was assessed by the hair cortisol concentration (HCC)
      (over a 3-month period). After controlling for potential confounders, low HCC
      predicted an increase in ADHD symptoms between the age of 4 and 5 years.
      Exploration of gender effects revealed that cross-sectional and predictive
      associations were significant in boys but not in girls. Low HCC might thus be
      regarded as an early marker of a possibly gender-related developmental pathway to
      ADHD.

PMID- 29570768
TI  - Tim-3 exacerbates kidney ischaemia/reperfusion injury through the TLR-4/NF-kappaB
      signalling pathway and an NLR-C4 inflammasome activation.
AB  - T cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), a
      member of the immunoglobulin superfamily, has been shown to play a crucial role
      in host adaptive immunity and tolerance. However, its role in kidney ischaemia
      reperfusion injury (IRI) remains unknown. In this study, we investigated the role
      and mechanism of Tim-3 signalling after kidney IRI. In an established murine
      model of kidney IRI, we found that Tim-3 expression is enhanced on
      monocytes/macrophages. Anti-Tim-3 antibody RMT3-23 ameliorates biochemical and
      histological kidney injury, reduces apoptosis and decreases macrophage
      infiltration and cytokine production in ischaemic kidneys. Cell culture
      experiments also demonstrated that the role of Tim-3 in IRI-induced macrophage
      activation leads to the secretion of proinflammatory cytokines and chemokines. In
      addition, Toll-like receptor (TLR)-4 and Nod-like receptor (NLR) family CARD
      domain-containing protein 4 (NLR-C4) expression were enhanced after kidney IRI
      and decreased significantly by RMT3-23. Tim-3 not only promotes TLR-mediated
      nuclear factor kappa B (NF-kappaB) activation and cytokine and chemokine release,
      but also participates in NLR-C4 inflammasome activation. Taken together, our data
      confirm that Tim-3 signalling enhances injury after kidney IRI and demonstrated
      that Tim-3 is involved in regulating TLR-4/NF-kappaB signalling and NLR-C4
      inflammasome activation, which provide evidence that Tim-3 signalling is critical
      for kidney IRI and may provide a new means to ameliorate kidney tissue immune
      responses in the clinics.

PMID- 29570770
TI  - Boosting phagocytosis and anti-inflammatory phenotype in microglia mediates
      neuroprotection by PPARgamma agonist MDG548 in Parkinson's disease models.
AB  - BACKGROUND AND PURPOSE: Microglial phenotype and phagocytic activity are
      deregulated in Parkinson's disease (PD). PPARgamma agonists are neuroprotective
      in experimental PD, but their role in regulating microglial phenotype and
      phagocytosis has been poorly investigated. We addressed it by using the PPARgamma
      agonist MDG548. EXPERIMENTAL APPROACH: Murine microglial cell line MMGT12 was
      stimulated with LPS and/or MDG548, and their effect on phagocytosis of
      fluorescent microspheres or necrotic neurons was investigated by flow cytometry.
      Cytokines and markers of microglia phenotype, such as mannose receptor C type 1;
      MRC1), Ym1 and CD68 were measured by elisa and fluorescent immunohistochemistry.
      Levels of Beclin-1, which plays a role in microglial phagocytosis, were measured
      by Western blotting. In the in vivo MPTP-probenecid (MPTPp) model of PD in mice,
      MDG548 was tested on motor impairment, nigral neurodegeneration, microglial
      activation and phenotype. KEY RESULTS: In LPS-stimulated microglia, MDG548
      increased phagocytosis of both latex beads and necrotic cells, up-regulated the
      expression of MRC1, CD68 and to a lesser extent IL-10, while blocking the LPS
      induced increase of TNF-alpha and iNOS. MDG548 also induced Beclin-1. Chronic
      MPTPp treatment in mice down-regulated MRC1 and TGF-beta and up-regulated TNF
      alpha and IL-1beta immunoreactivity in activated CD11b-positive microglia,
      causing the death of nigral dopaminergic neurons. MDG548 arrested MPTPp-induced
      cell death, enhanced MRC1 and restored cytokine levels. CONCLUSIONS AND
      IMPLICATIONS: This study adds a novel mechanism for PPARgamma-mediated
      neuroprotection in PD and suggests that increasing phagocytic activity and anti
      inflammatory markers may represent an effective disease-modifying approach.

PMID- 29570771
TI  - The non-biphenyl-tetrazole angiotensin AT1 receptor antagonist eprosartan is a
      unique and robust inverse agonist of the active state of the AT1 receptor.
AB  - BACKGROUND AND PURPOSE: Conditions such as hypertension and renal allograft
      rejection are accompanied by chronic, agonist-independent, signalling by
      angiotensin II AT1 receptors. The current treatment paradigm for these diseases
      entails the preferred use of inverse agonist AT1 receptor blockers (ARBs).
      However, variability in the inverse agonist activities of common biphenyl
      tetrazole ARBs for the active state of AT1 receptors often leads to treatment
      failure. Therefore, characterization of robust inverse agonist ARBs for the
      active state of AT1 receptors is necessary. EXPERIMENTAL APPROACH: To identify
      the robust inverse agonist for active state of AT1 receptors and its molecular
      mechanism, we performed site-directed mutagenesis, competition binding assay,
      inositol phosphate production assay and molecular modelling for both ground-state
      wild-type AT1 receptors and active-state N111G mutant AT1 receptors. KEY RESULTS:
      Although candesartan and telmisartan exhibited weaker inverse agonist activity
      for N111G- compared with WT-AT1 receptors, only eprosartan exhibited robust
      inverse agonist activity for both N111G- and WT- AT1 receptors. Specific ligand
      receptor contacts for candesartan and telmisartan are altered in the active-state
      N111G- AT1 receptors compared with the ground-state WT-AT1 receptors, suggesting
      an explanation of their attenuated inverse agonist activity for the active state
      of AT1 receptors. In contrast, interactions between eprosartan and N111G-AT1
      receptors were not significantly altered, and the inverse agonist activity of
      eprosartan was robust. CONCLUSIONS AND IMPLICATIONS: Eprosartan may be a better
      therapeutic option than other ARBs. Comparative studies investigating eprosartan
      and other ARBs for the treatment of diseases caused by chronic, agonist
      independent, AT1 receptor activation are warranted.

PMID- 29570772
TI  - Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic
      acid for the prevention of colorectal adenomas.
AB  - BACKGROUND: Aspirin may reduce the risk of several types of cancer. OBJECTIVES:
      To evaluate if folic acid is associated with risk of basal cell carcinoma (BCC).
      METHODS: BCC incidence was evaluated in a randomized, double-blind, placebo
      controlled clinical trial of aspirin (81 mg daily or 325 mg daily for ~3 years)
      and/or folic acid (1 mg daily for ~6 years) for the prevention of colorectal
      adenomas among 1121 participants with a previous adenoma. BCC was confirmed by
      blinded review of pathology reports. RESULTS: One hundred and four of 958 non
      Hispanic white participants were diagnosed with BCC over a median follow-up of
      13.5 years. Cumulative incidence of BCC was 12% [95% confidence interval (CI) 7
      17] for placebo, 16% (95% CI 11-21) for 81 mg aspirin daily and 15% (95% CI 10
      20) for 325 mg aspirin daily [hazard ratio (HR) for any aspirin 1.45 (95% CI 0.93
      2.26); HR for 81 mg daily 1.57 (95% CI 0.96-2.56); HR for 325 mg daily 1.33 (95%
      CI 0.80-2.20)]. BCC risk was higher with aspirin use in those without previous
      skin cancer but lower with aspirin use in those with previous skin cancer
      (Pinteraction = 0.02 for 81 mg aspirin daily; Pinteraction = 0.03 for 325 mg
      aspirin daily). Folic acid supplementation was unrelated to BCC incidence (HR
      0.85; 95% CI 0.57-1.27). CONCLUSIONS: Neither aspirin nor folic acid treatment
      had a statistically significant effect on risk of BCC. Subgroup analysis
      suggested that chemopreventive effects of nonsteroidal anti-inflammatory drugs
      may be specific to those at high risk for BCC.

PMID- 29570773
TI  - The FDA's Approach to the Prescription Opioid Problem.
AB  - Our nation's ongoing prescription opioid abuse crisis, amounting to over 78
      billion dollars in health and social costs annually,1 is a critical priority for
      the US Food and Drug Administration (FDA). As a part of our mission to support
      the safe and effective use of prescription medicines, the FDA is taking a fresh
      look at potential scientific and regulatory actions we can take to address this
      crisis.

PMID- 29570774
TI  - Application of the Mesolens for subcellular resolution imaging of intact larval
      and whole adult Drosophila.
AB  - In a previous paper, we showed a new giant lens called the Mesolens and presented
      performance data and images from whole fixed and intact fluorescently-stained
      12.5-day old mouse embryos. Here, we show that using the Mesolens we can image an
      entire Drosophila larva or adult fly in confocal epifluorescence and show
      subcellular detail in all tissues. By taking several hundreds of optical sections
      through the entire volume of the specimen, we show cells and nuclear details
      within the gut, brain, salivary glands and reproductive system that normally
      require dissection for study. Organs are imaged in situ in correct 3D
      arrangement. Imaginal discs are imaged in mature larvae and it proved possible to
      image pachytene chromosomes in cells within ovarian follicles in intact female
      flies. Methods for fixing, staining and clearing are given.

PMID- 29570775
TI  - Chemical Imaging of Cyanoacrylate-Fumed Fingerprints by Matrix-assisted Laser
      Desorption/Ionization Mass Spectrometry Imaging.
AB  - For new techniques to be incorporated into forensic science, they must be
      compatible with current practices. Here, cyanoacrylate fuming, a common
      development technique for latent fingerprints, is studied for its compatibility
      with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for
      chemical imaging of latent fingerprints. Half of a fingerprint was fumed while
      the other half was not; then, the changes in chemical composition and signal
      intensity were compared with MALDI-MS imaging. No evidence was found that
      fingerprint compounds are chemically altered by fuming or their signal
      intensities affected. The only exceptions were significant signal loss for
      quaternary ammonium compounds from hygiene products and moderate signal loss for
      tertiary amine compounds. This result is in striking contrast with the previous
      attempts by others, which is attributed to the difference in instrumentation.

PMID- 29570777
TI  - Fundamental Limits of Shaking a Baby.
AB  - Basic physics places limits on the mechanics involved in shaking a baby.
      Fundamental definitions and practical limitations are used to compare shaking
      with car crashes and low-level falls. First-order mathematical considerations
      applied to a 6-month-old infant determine an angular velocity limit for head
      rotation around 75 rad/s and maximum angular acceleration less than 1600 rad/s2
      without impact. By comparison, results from a low-level fall of 0.76 m (30
      inches) yield values of 83 rad/s and 13,000 rad/s2 in a practical worst-case
      scenario.

PMID- 29570776
TI  - The roles of resident, central and effector memory CD4 T-cells in protective
      immunity following infection or vaccination.
AB  - Immunological memory provides rapid protection to pathogens previously
      encountered through infection or vaccination. CD4 T-cells play a central role in
      all adaptive immune responses. Vaccines must, therefore, activate CD4 T-cells if
      they are to generate protective immunity. For many diseases, we do not have
      effective vaccines. These include human immunodeficiency virus (HIV),
      tuberculosis and malaria, which are responsible for many millions of deaths each
      year across the globe. CD4 T-cells play many different roles during the immune
      response coordinating the actions of many other cells. In order to harness the
      diverse protective effects of memory CD4 T-cells, we need to understand how
      memory CD4 T-cells are generated and how they protect the host. Here we review
      recent findings on the location of different subsets of memory CD4 T-cells that
      are found in peripheral tissues (tissue resident memory T-cells) and in the
      circulation (central and effector memory T-cells). We discuss the generation of
      these cells, and the evidence that demonstrates how they provide immune
      protection in animal and human challenge models.

PMID- 29570778
TI  - Secretory vesicles of immune cells contain only a limited number of interleukin 6
      molecules.
AB  - Immune cells communicate by releasing large quantities of cytokines. Although the
      mechanisms of cytokine secretion are increasingly understood, quantitative
      knowledge of the number of cytokines per vesicle is still lacking. Here, we
      measured with quantitative microscopy the release rate of vesicles potentially
      carrying interleukin-6 (IL-6) in human dendritic cells. By comparing this to the
      total secreted IL-6, we estimate that secretory vesicles contain about 0.5-3 IL-6
      molecules, but with a large spread among cells/donors. Moreover, IL-6 did not
      accumulate within most cells, indicating that synthesis and not trafficking is
      the bottleneck for IL-6 production. IL-6 accumulated in the Golgi apparatus only
      in ~ 10% of the cells. Understanding how immune cells produce cytokines is
      important for designing new immunomodulatory drugs.

PMID- 29570779
TI  - Surgical re-excision vs. observation for histologically dysplastic naevi: a
      systematic review of associated clinical outcomes.
AB  - BACKGROUND: The management of histologically dysplastic naevi (HDN) with re
      excision vs. observation remains controversial because of lack of evidence about
      associated melanoma outcomes. OBJECTIVES: To assess published data on the
      development of biopsy-site primary cutaneous melanoma among biopsy-proven HDN
      managed with either re-excision or observation. METHODS: A systematic review of
      all published data: a total of 5293 records were screened, 18 articles were
      assessed in full text and 12 studies met inclusion criteria. No controlled trials
      were identified. RESULTS: Most studies (11 of 12, 92%) were retrospective chart
      reviews, and one was both a cross-sectional and cohort study. Many studies (nine
      of 12, 75%) had no head-to-head comparison groups and either only reported HDN
      that were re-excised or observed. A total of 2673 (1535 observed vs. 1138 re
      excised) HDN of various grades were included. Follow-up varied between 2 weeks
      and 30 years. Nine studies reported that no melanomas developed. Eleven biopsy
      site melanomas developed across three of the studies, six among observed lesions
      (0.39%) and five among re-excised lesions (0.44%). CONCLUSIONS: Based upon the
      available evidence the rates of biopsy-site primary melanoma were similarly low
      among observed lesions and re-excised lesions. This suggests that HDNs can be
      observed with minimal adverse melanoma-associated outcomes. However, all included
      articles were of low quality and further prospective trials could better guide
      clinical decision making.

PMID- 29570781
TI  - The President's Commission on Combating Drug Addiction and the Opioid Crisis:
      Origins and Recommendations.
AB  - The United States has the ignominious distinction of leading the world in opioid
      prescribing,1 and in opioid-related overdose deaths. The Centers for Disease
      Control (CDC) estimates that over 40,000 people died of an opioid-related
      overdose, with fentanyl-related deaths exceeding those of heroin or prescription
      opioids.2 Opioid overdoses are now the leading cause of unintentional deaths in
      the US and of declining lifespan expectancies.3 With a worsening crisis, agencies
      of the US government and others produced an array of reports on the opioid
      crisis. Yet the death rate escalated further from 2010 to the present.

PMID- 29570780
TI  - Effects of ischemic post-conditioning on neuronal VEGF regulation and microglial
      polarization in a rat model of focal cerebral ischemia.
AB  - Ischemic postconditioning is increasingly being investigated as a therapeutic
      approach for cerebral ischemia. However, the majority of studies are focused on
      the acute protection of neurons per se. Whether and how postconditioning affects
      multiple cells in the recovering neurovascular unit remains to be fully
      elucidated. Here, we asked whether postconditioning may modulate help-me
      signaling between injured neurons and reactive microglia. Rats were subjected to
      100 min of focal cerebral ischemia, then randomized into a control versus
      postconditioning group. After 3 days of reperfusion, infarct volumes were
      significantly reduced in animals treated with postconditioning, along with better
      neurologic outcomes. Immunostaining revealed that ischemic postconditioning
      increased expression of vascular endothelial growth factor (VEGF) in neurons
      within peri-infarct regions. Correspondingly, we confirmed that VEGFR2 was
      expressed on Iba1-positive microglia/macrophages, and confocal microscopy showed
      that in postconditioned rats, these cells were polarized to a ramified morphology
      with higher expression of M2-like markers. Treating rats with a VEGF receptor 2
      kinase inhibitor negated these effects of postconditioning on
      microglia/macrophage polarization. In vitro, postconditoning after oxygen-glucose
      deprivation up-regulated VEGF release in primary neuron cultures, and adding VEGF
      to microglial cultures partly shifted their M2-like markers. Altogether, our
      findings support the idea that after postconditioning, injured neurons may
      release VEGF as a 'help-me' signal that promotes microglia/macrophage
      polarization into potentially beneficial phenotypes.

PMID- 29570782
TI  - Childhood neurodevelopmental disorders and risk of coercive sexual victimization
      in childhood and adolescence - a population-based prospective twin study.
AB  - BACKGROUND: Autism spectrum disorder (ASD), Attention-deficit/Hyperactivity
      disorder (ADHD), and other related neurodevelopmental disorders (NDDs) have, in
      some previous studies, been shown to increase the risk of being sexually
      victimized. However, no studies have examined whether the association is driven
      by a general NDD phenotype versus specific diagnoses, nor the etiology of the
      association. METHOD: Using a genetically informative, prospective design, we
      examined the association between ASD and ADHD in childhood and coercive sexual
      victimization up to age 18. A total of 4,500 children participating in the Child
      and Adolescent Twin Study in Sweden (CATSS) were rated by their parents on NDDs
      at age 9 or 12 years, and self-reported at age 18 on lifetime experiences of
      coercive sexual touching and/or coercive sex. First, we regressed sexual
      victimization on the NDDs. Second, we regressed sexual victimization on general
      and specific NDD symptoms identified via a bifactor model. Third, we decomposed
      the observed associations into genetic and environmental parts. RESULTS: In
      females, ASD was associated with an almost threefolded increased risk of coercive
      sexual victimization, and ADHD with a doubled risk. In males, the risk associated
      with ASD and ADHD was of the same magnitude but not significant. When controlling
      for overall NDD symptom load ASD or ADHD, no longer uniquely predicted coercive
      sexual victimization. The association between the NDD general factor and coercive
      sexual victimization was due to shared genetics. CONCLUSIONS: General NDD symptom
      load, rather than specific ASD or ADHD symptoms, seems to be a moderate
      vulnerability factor for coercive sexual victimization. We speculate that an
      evocative gene-environment correlation might account for this observation, such
      that sexual perpetrators actively target NDD individuals.

PMID- 29570783
TI  - Defining the role of NK cells during dengue virus infection.
AB  - In recent years, our understanding of the complex number of signals that need to
      be integrated between a diverse number of receptors present on natural killer
      (NK) cells and ligands present on target cells has improved. Here, we review the
      progress made in identifying interactions between dengue viral peptides presented
      on HLA Class 1 molecules with inhibitory and activating killer-like
      immunoglobulin receptors on NK cells, direct interactions of viral proteins with
      NK cell receptors, the involvement of dengue virus-specific antibodies in
      mediating antibody-dependent cell-mediated cytotoxicity and the role of soluble
      factors in modulating NK cell responses. We discuss findings of NK cell
      activation early after natural dengue infection, and point to the role that NK
      cells may play in regulating both innate and adaptive immune responses, in the
      context of our new appreciation of interactions of dengue virus with specific NK
      cell receptors. With a number of flavivirus vaccine candidates in clinical
      trials, how NK cells respond to attenuated dengue virus and subunit protein
      vaccine candidates and shape adaptive immunity will need to be considered.

PMID- 29570784
TI  - Origin context of trait data matters for predictions of community performance in
      a grassland biodiversity experiment.
AB  - Plant functional traits may explain the positive relationship between species
      richness and ecosystem functioning, but species-level trait variation in response
      to growth conditions is often ignored in trait-based predictions of community
      performance. In a large grassland biodiversity experiment (Jena Experiment), we
      measured traits on plants grown as solitary individuals, in monocultures or in
      mixtures. We calculated two measures of community-level trait composition, i.e.,
      community-weighted mean traits (CWM) and trait diversity (Rao's quadratic
      entropy; FD) based on different contexts in which traits were measured (trait
      origins). CWM and FD values of the different measurement origins were then
      compared regarding their power to predict community biomass production and
      biodiversity effects quantified with the additive partitioning method.
      Irrespective of trait origin, models combining CWM and FD values as predictors
      best explained community biomass and biodiversity effects. CWM values based on
      monoculture, mixture-mean or community-specific trait data were similarly
      powerful predictors, but predictions became worse when trait values originated
      from solitary-grown individuals. FD values based on monoculture traits were the
      best predictors of community biomass and net biodiversity effects, while FD
      values based on community-specific traits were the best predictors for
      complementarity and selection effects. Traits chosen as best CWM predictors were
      not strongly affected by trait origin but traits chosen as best FD predictors
      varied strongly dependent on trait origin and altered the predictability of
      community performance. We conclude that by adjusting their functional traits to
      species richness and even specific community compositions, plants can change
      community-level trait compositions, thereby also changing community biomass
      production and biodiversity effects. Incorporation of these plastic trait
      adjustments of plants in trait-based ecology can improve its predictive power in
      explaining biodiversity-ecosystem functioning relationships.

PMID- 29570792
TI  - Genomics studies on musical aptitude, music perception, and practice.
AB  - When searching for genetic markers inherited together with musical aptitude,
      genes affecting inner ear development and brain function were identified. The
      alpha-synuclein gene (SNCA), located in the most significant linkage region of
      musical aptitude, was overexpressed when listening and performing music. The GATA
      binding protein 2 gene (GATA2) was located in the best associated region of
      musical aptitude and regulates SNCA in dopaminergic neurons, thus linking DNA-
      and RNA-based studies of music-related traits together. In addition to SNCA,
      several other genes were linked to dopamine metabolism. Mutations in SNCA
      predispose to Lewy-body dementia and cause Parkinson disease in humans and affect
      song production in songbirds. Several other birdsong genes were found in
      transcriptome analysis, suggesting a common evolutionary background of sound
      perception and production in humans and songbirds. Regions of positive selection
      with musical aptitude contained genes affecting auditory perception, cognitive
      performance, memory, human language development, and song perception and
      production of songbirds. The data support the role of dopaminergic pathway and
      their link to the reward mechanism as a molecular determinant in positive
      selection of music. Integration of gene-level data from the literature across
      multiple species prioritized activity-dependent immediate early genes as
      candidate genes in musical aptitude and listening to and performing music.

PMID- 29570791
TI  - Patient Enrichment for Precision-Based Cancer Clinical Trials: Using Prospective
      Cohort Surveillance as an Approach to Improve Clinical Trials.
AB  - Technological advances have led to the identification of biomarkers and
      development of novel target-based therapies. While some novel therapies have
      improved patient outcomes, the prevalence and diversity of biomarkers and targets
      in patient populations, especially patients with cancer, has created a challenge
      for the design and performance of clinical trials. To address this challenge we
      propose that prospective cohort surveillance of patients may be a solution to
      promote clinical trial matching for patients in need.

PMID- 29570793
TI  - Relationship of premenstrual and menstrual symptoms to alexithymia among nursing
      students.
AB  - PURPOSE: The aim of this study is to determine the relationship of premenstrual
      and menstrual symptoms to alexithymia among nursing students. DESIGN AND METHODS:
      This descriptive study was conducted with 284 undergraduate nursing students.
      Data were collected using Premenstrual Syndrome Scale (PMSS), Menstrual Symptom
      Scale (MSQ), and Toronto Alexithymia Scale-20 (TAS-20). FINDINGS: The PMSS, MSQ,
      and TAS-20 mean scores were 103.56 +/- 35.08, 2.92 +/- 0.8, and 45.22 +/- 9.17,
      respectively. There was statistically significant positive correlation between
      TAS-20 and PMSS and MSQ mean scores (p < .05). PRACTICAL IMPLICATIONS: Women
      should be evaluated for alexithymia to prevent the adverse effects of
      premenstrual and menstrual symptoms.

PMID- 29570794
TI  - Understanding deregulated cellular and molecular dynamics in the haematopoietic
      stem cell niche to develop novel therapeutics for bone marrow fibrosis.
AB  - Bone marrow fibrosis is the continuous replacement of blood-forming cells in the
      bone marrow with excessive scar tissue, leading to failure of the body to produce
      blood cells and ultimately to death. Myofibroblasts are fibrosis-driving cells
      and are well characterized in solid organ fibrosis, but their role and cellular
      origin in bone marrow fibrosis have remained obscure. Recent work has
      demonstrated that Gli1+ and leptin receptor+ mesenchymal stromal cells are
      progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic
      ablation or pharmacological inhibition of Gli1+ mesenchymal stromal cells
      ameliorated fibrosis in mouse models of myelofibrosis. Conditional deletion of
      the platelet-derived growth factor (PDGF) receptor-alpha (PDGFRA) gene (Pdgfra)
      and inhibition of PDGFRA by imatinib in leptin receptor+ stromal cells suppressed
      their expansion and ameliorated bone marrow fibrosis. Understanding the cellular
      and molecular mechanisms in the haematopoietic stem cell niche that govern the
      mesenchymal stromal cell-to-myofibroblast transition and myofibroblast expansion
      will be critical to understand the pathogenesis of bone marrow fibrosis in both
      malignant and non-malignant conditions, and will guide the development of novel
      therapeutics. In this review, we summarize recent discoveries of mesenchymal
      stromal cells as part of the haematopoietic niche and as myofibroblast
      precursors, and discuss potential therapeutic strategies in the specific
      targeting of fibrotic transformation in bone marrow fibrosis. (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- 29570795
TI  - Cortical progenitor biology: key features mediating proliferation versus
      differentiation.
AB  - The cerebral cortex is a highly organized structure whose development depends on
      diverse progenitor cell types, namely apical radial glia, intermediate
      progenitors, and basal radial glia cells, which are responsible for the
      production of the correct neuronal output. In recent years, these progenitor cell
      types have been deeply studied, particularly basal radial glia and their role in
      cortical expansion and gyrification. We review here a broad series of factors
      that regulate progenitor behavior and daughter cell fate. We first describe the
      different neuronal progenitor types, emphasizing the differences between
      lissencephalic and gyrencephalic species. We then review key factors shown to
      influence progenitor proliferation versus differentiation, discussing their roles
      in progenitor dynamics, neuronal production, and potentially brain size and
      complexity. Although spindle orientation has been considered a critical factor
      for mode of division and daughter cell output, we discuss other features that are
      emerging as crucial for these processes such as organelle and cell cycle
      dynamics. Additionally, we highlight the importance of adhesion molecules and the
      polarity complex for correct cortical development. Finally, we briefly discuss
      studies assessing progenitor multipotency and its possible contribution to the
      production of specific neuronal populations. This review hence summarizes recent
      aspects of cortical progenitor cell biology, and pinpoints emerging features
      critical for their behavior.

PMID- 29570796
TI  - Do beliefs about depression etiologies influence the type and severity of
      depression stigma? The case of Arab adolescents.
AB  - PURPOSE: Research has documented that holding certain etiological beliefs about
      depression can determine the level of stigma experienced by individuals with
      depression. To date, no studies have yet examined this relationship among
      adolescents. Using a sample of Arab adolescents, the purpose of this study was to
      describe adolescents' beliefs about the etiology of depression, and examine
      whether these beliefs influence the type and severity of depression stigma.
      METHODS: A nationwide school survey was conducted in a representative sample of
      Jordanian public and private schools located in Jordan, a Middle-Eastern Arab
      country. A total of 2,349 adolescents aged 12-17 (59% female) completed and
      returned an anonymous survey that included measures on adolescents'
      sociodemographic and health characteristics, depression symptoms, depression
      stigma, and depression etiological beliefs. An exploratory factor analysis with
      principal components analysis (PCA) was used to examine the factor structure of
      the Depression Etiological Beliefs Scale. The stability of the PCA findings was
      tested using a cross-validation method. Regression analyses were performed to
      examine whether depression etiological beliefs, depression severity, or their
      interaction are associated with depression stigma. RESULTS: Adolescents endorsed
      multiple etiological beliefs about depression. The beliefs in which likely or
      very likely was most often reported were stressful events in one's life (72%),
      social factors (65%), and one's weak will (56%). On the other hand, the least
      reported beliefs were genetic or inherited problems (24%), chemical imbalance
      (30%), and punishment for wrong doings (35%). The interaction between
      adolescents' depression severity and depression beliefs significantly predicted
      personal stigma. Adolescent sex, age, and region of residence significantly
      affected the relationship between depression beliefs and stigma. CONCLUSIONS:
      Nurses need to consider the beliefs and attitudes their patients have around
      depression, as these can influence symptom severity, comprehensive treatment
      plans, and adherence to provider recommendations. This study provides a better
      understanding of how depression beliefs affect Jordanian adolescents' attitudes
      toward depression, which can guide intervention programs to increase awareness
      about depression and promote treatment utilization.

PMID- 29570797
TI  - Fetal hydrometrocolpos and congenital imperforate hymen: Prenatal and postnatal
      imaging features.
AB  - Congenital imperforate hymen is probably the most common obstructive anomaly of
      the female reproductive tract. The accumulation of fluid in the genital tract
      leads to a distended uterus and vagina, causing hydrometrocolpos. Prenatal
      diagnosis of fetal hydrometrocolpos is uncommon, with only 22 cases reported in
      the literature and only a few cases of prenatal imaging of this condition
      available to date. The main ultrasound finding is a fetal pelvic mass posterior
      to the bladder and anterior to the rectum. We present the case of a 37-week
      female fetus with a fetal pelvic mass detected in a routine obstetric ultrasound
      examination, and the correlation between the prenatal and postnatal findings.

PMID- 29570798
TI  - Microsurgical instrument-assisted facial nerve dissection for deep lobe parotid
      tumors.

PMID- 29570799
TI  - Ketogenic Diet Based on Extra Virgin Coconut Oil Has No Effects in Young Wistar
      Rats With Pilocarpine-Induced Epilepsy.
AB  - This study evaluated the effects of a ketogenic diet (KD) based on extra virgin
      coconut oil (Cocos nucifera L., VCO), on the treatment of epileptic rats. Two
      sets of experiments were conducted. First, male Wistar rats underwent induction
      of status epilepticus (SE) with the administration of pilocarpine
      intraperitoneally 21 animals reached spontaneous recurrent seizures (SRS) and
      were randomly allocated to the dietary regimens and video-monitored for 19 days.
      In the second experiment, 24 animals were randomized immediately after the
      induction of SE and followed for 67 days. Diets were as follows: Control (AIN
      93G; 7% lipid), KetoTAGsoya (KD based on soybean oil; 69.79% lipid), and
      KetoTAGcoco (KD based on VCO; 69.79% lipid). There were no differences in the
      latency to the first crisis, total frequency, and duration of the SRS between
      groups in 2 experiments. The data suggest no effects of KD, with or without VCO,
      in rats with pilocarpine-induced epilepsy.

PMID- 29570801
TI  - Predictive factors in 995 stapes surgeries for primary otosclerosis.
AB  - OBJECTIVES/HYPOTHESIS: This study sought to identify the predictors of outcome in
      patients with otosclerosis undergoing primary stapes surgery. STUDY DESIGN:
      Retrospective analysis of medical records. METHODS: A total of 995 patients with
      otosclerosis who underwent primary stapes surgery by a single surgeon between
      January 2006 and December 2016 were included. Logistic regression analysis was
      performed to examine factors affecting postoperative hearing thresholds at
      individual frequencies. A postoperative air-bone gap (ABG) closure <= 10 dB in
      the stapes surgery was considered as excellent outcome. RESULTS: Stapedotomies
      and stapedectomies were conducted in 823 and 172 ears, respectively. The
      surgeries had an overall success rate of 93.6%. Univariate analysis showed a
      significantly higher success rate in patients with larger prostheses (diameter =
      0.6 mm). According to the results of multivariate logistic regression analysis,
      preoperative ABG (B coefficient = -0.10), bilaterality (odds ratio [OR] = 2.09),
      right ear involvement (OR = 2.00), female gender (OR = 1.81), and nonobliterative
      footplate (OR = 3.69) were significant prognostic factors predicting excellent
      outcome. CONCLUSIONS: Our findings indicated that the functional results were
      generally good. Based on logistic regression analysis, preoperative ABG and
      nonobliterative footplate were the most important predictors of hearing outcome
      after stapes surgery for otosclerosis. The success of the surgery did not depend
      on the procedure types (stapedotomy vs. stapedectomy) or the diameter of the
      prosthesis (0.4 mm vs. 0.6 mm). LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2403
      2407, 2018.

PMID- 29570802
TI  - Antibiotic resistance in severe odontogenic infections of the South Australian
      population: a 9-year retrospective audit.
AB  - BACKGROUND: The aims of this study were to evaluate the microbiological trends in
      severe odontogenic infections requiring hospital admission in the South
      Australian Oral and Maxillofacial Surgery Unit. Rates of antibiotic resistance to
      empirical antibiotic regimens were determined to quantify the clinical
      implications of antibiotic-resistant odontogenic infections. METHODS: A
      retrospective case audit was performed on all odontogenic infections admitted to
      the Royal Adelaide Hospital over a 9-year period. Data was collected regarding
      demographics, microbiological culture and sensitivity results, and clinical
      outcome variables. RESULTS: Of a total of 672 patients, microbiology data was
      available for 447 cases. Penicillin-resistant organisms were identified in 10.8%
      of patients, who required a significantly longer length of hospital admission
      (mean, 9.93 days) and higher rates of non-response to initial surgical therapy
      (40%). CONCLUSIONS: There were moderate rates of antibiotic-resistant odontogenic
      infections within the South Australian population. Patients within this subgroup
      demonstrate markedly poorer clinical outcomes. Effective treatment of odontogenic
      infections involves early operative intervention, with adjunctive use of
      appropriate antibiotic therapy that involves close monitoring of response to
      removal of the cause and use of first-line antibiotic agents. Cases that fail to
      respond require urgent specialist review in order to reduce morbidity and
      mortality outcomes.

PMID- 29570800
TI  - DNA methylation of microRNA-coding genes in non-small-cell lung cancer patients.
AB  - Deregulated DNA methylation leading to transcriptional inactivation of certain
      genes occurs frequently in non-small-cell lung cancers (NSCLCs). As well as
      protein-coding genes, microRNA (miRNA)-coding genes may be targets for
      methylation in NSCLCs; however, the number of known methylated miRNA genes is
      still small. Thus, we investigated methylation of miRNA genes in primary tumour
      (TU) samples and corresponding non-malignant lung tissue (NL) samples of 50 NSCLC
      patients by using methylated DNA immunoprecipitation followed by custom-designed
      tiling microarray analyses (MeDIP-chip), and 252 differentially methylated probes
      between TU samples and NL samples were identified. These probes were annotated,
      which resulted in the identification of 34 miRNA genes with increased methylation
      in TU samples. Some of these miRNA genes were already known to be methylated in
      NSCLCs (e.g. those encoding miR-9-3 and miR-124), but methylation of the vast
      majority of them was previously unknown. We selected six miRNA genes (those
      encoding miR-10b, miR-1179, miR-137, miR-572, miR-3150b, and miR-129-2) for gene
      specific methylation analyses in TU samples and corresponding NL samples of 104
      NSCLC patients, and observed a statistically significant increase in methylation
      of these genes in TU samples (p < 0.0001). In silico target prediction of the six
      miRNAs identified several oncogenic/cell proliferation-promoting factors (e.g.
      CCNE1 as an miR-1179 target). To investigate whether miR-1179 indeed targets
      CCNE1, we transfected miR-1179 gene mimics into CCNE1-expressing NSCLC cells, and
      observed downregulated CCNE1 mRNA expression in these cells as compared with
      control cells. Similar effects on cyclin E1 expression were seen in western blot
      analyses. In addition, we found a statistically significant reduction in the
      growth of NSCLC cells transfected with miR-1179 mimics as compared with control
      cells. In conclusion, we identified many methylated miRNA genes in NSCLC
      patients, and found that the miR-1179 gene is a potential tumour cell growth
      suppressor in NSCLCs. Overall, our findings emphasize the impact of miRNA gene
      methylation on the pathogenesis of NSCLCs. (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- 29570803
TI  - Facial hyperalgesia due to direct action of endothelin-1 in the trigeminal
      ganglion of mice.
AB  - OBJECTIVE: This study assessed the ability of endothelin-1 (ET-1) to evoke heat
      hyperalgesia when injected directly into the trigeminal ganglia (TG) of mice and
      determined the receptors implicated in this effect. The effects of TG ETA and ETB
      receptor blockade on alleviation of heat hyperalgesia in a model of trigeminal
      neuropathic pain induced by infraorbital nerve constriction (CION) were also
      examined. METHODS: Naive mice received an intraganglionar (i.g.) injection of ET
      1 (0.3-3 pmol) or the selective ETB R agonist sarafotoxin S6c (3-30 pmol), and
      response latencies to ipsilateral heat stimulation were assessed before the
      treatment and at 1-h intervals up to 5 h after the treatment. Heat hyperalgesia
      induced by i.g. ET-1 or CION was assessed after i.g. injections of ETA R and ETB
      R antagonists (BQ-123 and BQ-788, respectively, each at 0.5 nmol). KEY FINDINGS:
      Intraganglionar ET-1 or sarafotoxin S6c injection induced heat hyperalgesia
      lasting 4 and 2 h, respectively. Heat hyperalgesia induced by ET-1 was attenuated
      by i.g. BQ-123 or BQ-788. On day 5 after CION, i.g. BQ-788 injection produced a
      more robust antihyperalgesic effect compared with BQ-123. CONCLUSIONS: ET-1
      injection into the TG promotes ETA R/ETB R-mediated facial heat hyperalgesia, and
      both receptors are clearly implicated in CION-induced hyperalgesia in the murine
      TG system.

PMID- 29570804
TI  - Effects of an empowerment program for community-dwelling people with mental
      illness in South Korea.
AB  - PURPOSE: This study aimed to examine the effects of an empowerment program on
      empowerment, quality of life, and recognition of human rights of people with
      mental illness residing in a community in South Korea. DESIGN AND METHODS: A
      repeated-measures design (before, immediately after, and 4 weeks after the
      intervention) with a control group was used. The experimental group received an
      eight-session empowerment program over 8 weeks. FINDINGS: The empowerment program
      significantly increased empowerment and quality of life, but not recognition of
      human rights. PRACTICE IMPLICATIONS: Nursing interventions should be developed to
      enhance the recognition of human rights for people with mental illness.

PMID- 29570805
TI  - Algorithm Analysis of the DSM-5 Alcohol Withdrawal Symptom.
AB  - BACKGROUND: Alcohol withdrawal (AW) is an important clinical and diagnostic
      feature of alcohol dependence. AW has been found to predict a worsened course of
      illness in clinical samples, but in some community studies, AW endorsement rates
      are strikingly high, suggesting false-positive symptom assignments. Little
      research has examined the validity of the DSM-5 algorithm for AW, which requires
      either the presence of at least 2 of 8 subcriteria (i.e., autonomic
      hyperactivity, tremulousness, insomnia, nausea, hallucinations, psychomotor
      agitation, anxiety, and grand mal seizures), or, the use of alcohol to avoid or
      relieve these symptoms. METHODS: We used item and algorithm analyses of data from
      waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related
      Conditions (current drinkers, n = 26,946 at wave 1) to study the validity of DSM
      5 AW as operationalized by the Alcohol Use Disorder and Associated Disabilities
      Interview Schedule-DSM-IV (AUDADIS-IV). RESULTS: A substantial proportion of
      individuals given the AW symptom reported only modest to moderate levels of
      alcohol use and alcohol problems. Alternative AW algorithms were superior to DSM
      5 in terms of levels of alcohol use and alcohol problem severity among those with
      AW, group difference effect sizes, and predictive validity at a 3-year follow-up.
      The superior alternative algorithms included those that excluded the nausea
      subcriterion; required withdrawal-related distress or impairment; increased the
      AW subcriteria threshold from 2 to 3 items; and required tremulousness for AW
      symptom assignment. CONCLUSIONS: The results indicate that the DSM-5 definition
      of AW, as assessed by the AUDADIS-IV, has low specificity. This shortcoming can
      be addressed by making the algorithm for symptom assignment more stringent.

PMID- 29570806
TI  - Preparation of citrus pectin gels by power ultrasound and its application as an
      edible coating in strawberries.
AB  - BACKGROUND: Pectin is heteropolysaccharide found in cell walls originating mainly
      from by-products, as well as citrus peels, apple and sugar beet pulp, and
      presenting biological and techno-functional properties. In the present study, a
      general and structural characterisation of industrial citrus pectins was
      performed together with a study of impact of power ultrasound (US) on their
      rheological properties, with the aim of using them as edible coatings for fresh
      strawberries. RESULTS: The results obtained indicated that pure pectin showed a
      methylesterification degree greater than 50% and galacturonic acid content > 65%,
      supporting its consideration as additive E-440; such conditions were not achieved
      in pectin with sugar addition. Furthermore, in the rheological study, pectin gels
      showed a non-Newtonian flow and pseudoplastic behaviour and presented different
      viscosity ranges depending on the preparation methods, including power US. Gels
      were used as edible coatings for fresh strawberries aiming to improve their
      quality during storage over a period of 5 days, controlling quality
      characteristics such as humidity loss, acidity and colour parameters (L*, a*, b*,
      C, h degrees , DeltaE). CONCLUSION: The results obtained demonstrate that US
      treatments give rise to pectin gels that can improve the quality of strawberries
      over their lifetime. (c) 2018 Society of Chemical Industry.

PMID- 29570807
TI  - Panel of serum protein biomarkers to grade the severity of traumatic brain
      injury.
AB  - The Glasgow Coma Scale (GCS), which classifies patients into mild, moderate or
      severe traumatic brain injury (TBI), is a system used to prioritize treatment and
      prognosticate the severity of head injury. In this study, sera of patients with
      various stages of TBI, as well as control subjects, were analyzed to screen for
      proteins that may be used to complement the GCS system. By subjecting pooled
      serum samples to iTRAQ analysis for quantitative comparison of protein abundance,
      and attesting their altered levels using ELISA, we have detected increased levels
      of serum amyloid A, C-reactive protein, leucine-rich alpha-2-glycoprotein,
      lipopolysaccharide-binding protein, fibronectin, vitronectin and alpha-1
      antichymotrypsin in patients across all strata of TBI relative to the controls.
      However, kininogen was decreased only in moderate and severe TBI, whereas
      apolipoprotein E and zinc-alpha-2-glycoprotein were only increased in severe TBI.
      Hence, we propose a panel of serum biomarkers, which if analyzed within 24 h of
      the injury, can be used to diagnose patients with TBI into mild, moderate or
      severe stratification objectively, thus complementing the traditional GCS.

PMID- 29570808
TI  - An independent validation study of loci associated with nematode resistance in
      sheep.
AB  - Gastrointestinal nematode infection is a constraint on sheep production
      worldwide. Selective breeding programmes to enhance resistance to nematode
      infection are currently being implemented in a number of countries.
      Identification of loci associated with resistance to infection or causative
      mutations for resistance would enable more effective selection. Loci associated
      with indicator traits for nematode resistance has been identified in previous
      studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to
      validate the effects at eight genomic regions previously associated with nematode
      resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated
      with nematode resistance at the region-wide level but seven SNPs in three of the
      regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count
      in this study and six of these were also significant when fitted as single SNP
      effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7
      and 12.

PMID- 29570809
TI  - Impact of joint statistical dual-energy CT reconstruction of proton stopping
      power images: Comparison to image- and sinogram-domain material decomposition
      approaches.
AB  - PURPOSE: The purpose of this study was to assess the performance of a novel dual
      energy CT (DECT) approach for proton stopping power ratio (SPR) mapping that
      integrates image reconstruction and material characterization using a joint
      statistical image reconstruction (JSIR) method based on a linear basis vector
      model (BVM). A systematic comparison between the JSIR-BVM method and previously
      described DECT image- and sinogram-domain decomposition approaches is also
      carried out on synthetic data. METHODS: The JSIR-BVM method was implemented to
      estimate the electron densities and mean excitation energies (I-values) required
      by the Bethe equation for SPR mapping. In addition, image- and sinogram-domain
      DECT methods based on three available SPR models including BVM were implemented
      for comparison. The intrinsic SPR modeling accuracy of the three models was first
      validated. Synthetic DECT transmission sinograms of two 330 mm diameter phantoms
      each containing 17 soft and bony tissues (for a total of 34) of known composition
      were then generated with spectra of 90 and 140 kVp. The estimation accuracy of
      the reconstructed SPR images were evaluated for the seven investigated methods.
      The impact of phantom size and insert location on SPR estimation accuracy was
      also investigated. RESULTS: All three selected DECT-SPR models predict the SPR of
      all tissue types with less than 0.2% RMS errors under idealized conditions with
      no reconstruction uncertainties. When applied to synthetic sinograms, the JSIR
      BVM method achieves the best performance with mean and RMS-average errors of less
      than 0.05% and 0.3%, respectively, for all noise levels, while the image- and
      sinogram-domain decomposition methods show increasing mean and RMS-average errors
      with increasing noise level. The JSIR-BVM method also reduces statistical SPR
      variation by sixfold compared to other methods. A 25% phantom diameter change
      causes up to 4% SPR differences for the image-domain decomposition approach,
      while the JSIR-BVM method and sinogram-domain decomposition methods are
      insensitive to size change. CONCLUSION: Among all the investigated methods, the
      JSIR-BVM method achieves the best performance for SPR estimation in our
      simulation phantom study. This novel method is robust with respect to sinogram
      noise and residual beam-hardening effects, yielding SPR estimation errors
      comparable to intrinsic BVM modeling error. In contrast, the achievable SPR
      estimation accuracy of the image- and sinogram-domain decomposition methods is
      dominated by the CT image intensity uncertainties introduced by the
      reconstruction and decomposition processes.

PMID- 29570810
TI  - Laryngeal mask airway and transient hypercapnic hyperpnea for video-endoscopic
      assessment of unilateral laryngeal paralysis in dogs.
AB  - OBJECTIVE: To evaluate the ability to assess laryngeal function and to diagnose
      unilateral laryngeal paralysis (uLP) via airway endoscopy and carbon dioxide (CO2
      ) stimulation. STUDY DESIGN: Experimental study. ANIMALS: Six healthy, adult
      beagles. METHODS: Dogs were anesthetized with sevoflurane and dexmedetomidine.
      Laryngeal activity was observed via endoscopy placed through a laryngeal mask
      airway (LMA). The absolute and normalized glottic gap areas (AGGA and NGGA,
      respectively) and the glottic length (GL) were measured at inspiration and before
      and after surgically induced uLP. Measurements were obtained at eupnea and during
      hypercapnic hyperpnea produced by the administration of CO2 . Values for each
      hemilarynx were also measured. Video recordings were observed by 2 surgeons who
      scored function as normal or uLP. RESULTS: The AGGA and NGGA increased similarly
      during CO2 administration in intact dogs and in dogs with uLP; the GL increased
      in dogs with uLP but not in intact dogs. The AGGA and NGGA of the intact
      hemilarynx increased more than those of the affected hemilarynx in dogs with uLP.
      uLP was correctly identified more frequently by observers at hypercapnic
      hyperpnea than during eupnea. CONCLUSION: The increase in AGGA and NGGA at peak
      inspiration during CO2 administration was not limited by uLP, but asymmetry in
      hemilarynx AGGA and NGGA was observed in dogs with uLP. CO2 administration
      facilitated the identification of uLP. CLINICAL SIGNIFICANCE: Laryngeal endoscopy
      through an LMA coupled with administration of CO2 in anesthetized dogs
      facilitates the observation of arytenoid function and may improve the diagnosis
      of naturally occurring mild laryngeal paralysis.

PMID- 29570811
TI  - Detection on pharyngeal wall floppiness in patients with nonstructural factor
      induced obstructive sleep apnea-hypopnea syndrome: Difference in position
      detection.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate changes in pharyngeal wall floppiness (PWF)
      between patients with obstructive sleep apnea-hypopnea syndrome induced by non
      upper-airway structural factors and normal subjects, as well as the clinical
      significance using acoustic pharyngealmetry technology. STUDY DESIGN: Cohort
      study. METHODS: The obstructive sleep apnea (OSA) group (n = 102) and the normal
      control group (n = 50) were identified using the Eccovision Acoustic
      Pharyngometer measuring instrument. The volume of the pharyngeal cavity in the
      sitting and supine positions during expiration and inspiration was recorded,
      respectively, and the PWF index in the sitting and supine positions was
      calculated for further statistical analysis. RESULTS: PWF in the sitting (P <
      .001) and supine positions (P < .001) in the OSA group was notably higher than
      that in the control group. PWF in the supine position in both the OSA group and
      control group was remarkably higher than that in the sitting position (P < .001,
      P = .025, respectively). The difference in PWF between the supine and sitting
      positions (DeltaPWF) (PWF_supine-PWF_sit) was distinctly higher than in control
      group (P < .01). PWF was positively correlated with age (P < .001) but not with
      body mass index (P > .05). CONCLUSIONS: PWF, quantified as elevated PWF, is an
      important nonstructural factor for the pathogenesis of OSA patients. PWF in the
      supine position can more accurately reflect airway collapsibility in OSA
      patients. Our pilot study of a novel observation may help us in the choice of
      proper surgical candidates for OSA procedures. LEVEL OF EVIDENCE: 3b
      Laryngoscope, 128:2200-2205, 2018.

PMID- 29570812
TI  - Treatment planning based on lung functional avoidance is not ready for clinical
      deployment.

PMID- 29570813
TI  - In Vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in
      CRSw NP Patients.
AB  - OBJECTIVES: Among the predisposing factors implicated in the immune response to
      airway bacterial infections, genetic variations of the bitter taste receptor
      TAS2R38, which is expressed in the cilia of the human sinonasal epithelial cells,
      seem to be associated with susceptibility to chronic rhinosinusitis (CRS) and in
      vitro biofilm formation. Polymorphisms in TAS2R38 generate two common haplotypes:
      the nonfunctional AVI (Alanine, Valine, Isoleucine) and the functional PAV
      (Proline, Alanine, Valine) alleles, with the latter protecting against gram
      negative sinonasal infections. The aim of this study is to investigate for the
      first time the relevance of TAS2R38 genetic variants in the susceptibility to
      bacterial infections associated with in vivo biofilm formation in chronic
      rhinosinusitis with nasal polyps (CRSwNP) patients. STUDY DESIGN: A prospective
      study on 100 adult patients undergoing functional endoscopic sinus surgery (FESS)
      for CRSwNP. METHODS: Propylthiouracile (PROP) testing and TAS2R38 genotyping were
      applied to characterize patients for receptor functionality. Sinonasal mucosa
      samples were processed for microbiological examination and biofilm detection.
      RESULTS: The nonfunctional genotype is more frequent among CRS patients than in
      the general population (25% vs. 18.4%, P = 0.034). Airway gram-negative
      infections are primarily associated with the AVI haplotype (88.9% vs. 11.1%
      PAV/PAV-functional genotype, P = 0.023). Biofilm formation is prevalent in CRS
      patients with the AVI nontaster phenotype (62.5% vs. 33.3% PAV taster or
      supertaster phenotype, P = 0.05). CONCLUSION: Our findings confirm an inverse
      correlation between TAS2R38 functionality and gram-negative infections in Italian
      patients with CRSwNP. In addition, for the first time we demonstrated a
      relationship between in vivo microbial biofilm and TAS2R38 receptor variants.
      LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:E339-E345, 2018.

PMID- 29570814
TI  - Using stable distributions to characterize proton pencil beams.
AB  - PURPOSE: To introduce and evaluate the use of stable distributions as a
      methodology to quantify the behavior of proton pencil beams in a medium. METHODS:
      The proton pencil beams of a clinically commissioned proton treatment facility
      are replicated in a Monte Carlo simulation system (FLUKA). For each available
      energy, the beam deposition in water medium is characterized by the dose
      deposition. Using a stable distribution methodology, each beam with a nominal
      energy E is characterized by the lateral spread at depth z: S(z; alpha, gamma, E)
      and a total energy deposition ID (z, E). The parameter alpha describes the
      tailedness of the distributions, while gamma is used to scale the size of the
      function. The beams can then be described completely by a function of the
      variation of the parameters with depth. RESULTS: Quantitatively, the fit of the
      stable distributions, compared to those implemented in some standard treatment
      planning systems, are equivalent for all but the highest energies (i.e., 230
      MeV/u). The decrease in goodness of fit makes this methodology comparable to a
      double Gaussian approach. The introduction of restricted linear combinations of
      stable distributions also resolves that particular case. More importantly, the
      meta-parameterization (i.e., the description of the dose deposition by only
      providing the fitted parameters) allows for interpolation of nonmeasured data. In
      the case of the clinical commissioning data used in this paper, it was possible
      to only commission one out of five nominal energies to obtain a viable dataset,
      valid for all energies. An additional parameter beta allows to describe
      asymmetric beam profiles as well. CONCLUSIONS: Stable distributions are
      intrinsically suited to describe proton pencil beams in a medium and provide a
      tool to quantify the propagation of proton beams in a medium.

PMID- 29570815
TI  - Identifying auditory cortex encoding abnormalities in schizophrenia: The utility
      of low-frequency versus 40 Hz steady-state measures.
AB  - Magnetoencephalography (MEG) and EEG have identified poststimulus low frequency
      and 40 Hz steady-state auditory encoding abnormalities in schizophrenia (SZ).
      Negative findings have also appeared. To identify factors contributing to these
      inconsistencies, healthy control (HC) and SZ group differences were examined in
      MEG and EEG source space and EEG sensor space, with better group differentiation
      hypothesized for source than sensor measures given greater predictive utility for
      source measures. Fifty-five HC and 41 chronic SZ were presented 500 Hz sinusoidal
      stimuli modulated at 40 Hz during simultaneous whole-head MEG and EEG. MEG and
      EEG source models using left and right superior temporal gyrus (STG) dipoles
      estimated trial-to-trial phase similarity and percent change from prestimulus
      baseline. Group differences in poststimulus low-frequency activity and 40 Hz
      steady-state response were evaluated. Several EEG sensor analysis strategies were
      also examined. Poststimulus low-frequency group differences were observed across
      all methods. Given an age-related decrease in left STG 40 Hz steady-state
      activity in HC (HC > SZ), 40 Hz steady-state group differences were evident only
      in younger participants' source measures. Findings thus indicated that optimal
      data collection and analysis methods depend on the auditory encoding measure of
      interest. In addition, whereas results indicated that HC and SZ auditory encoding
      low-frequency group differences are generally comparable across modality and
      analysis strategy (and thus not dependent on obtaining construct-valid measures
      of left and right auditory cortex activity), 40 Hz steady-state group-difference
      findings are much more dependent on analysis strategy, with 40 Hz steady-state
      source-space findings providing the best group differentiation.

PMID- 29570817
TI  - Red blood cell alloimmunization in sickle cell disease: assessment of transfusion
      protocols during two time periods.
AB  - BACKGROUND: Prevention of red blood cell (RBC) alloimmunization in patients with
      sickle cell disease (SCD) focuses on phenotypic RBC matching. We assessed
      alloimmunization among transfused patients with SCD after implementing
      leukoreduction and prophylactic antigen matching (PAM). STUDY DESIGN AND METHODS:
      Retrospective review of transfusion and medical records for SCD patients 18
      months to 81 years of age was performed covering two 5-year periods: Period 1, no
      PAM, occasional leukoreduction, and Period 2, consistent leukoreduction and
      extended PAM (Rh, Kell, S, Fy, Jk) for patients already alloimmunized. Patients
      transfused in Period 1 were excluded from Period 2. RESULTS: A total of 293
      patients were transfused in Period 1 and 183 in Period 2. Median time between
      first sample and last type and screen after transfusion was 2.12 years in Period
      1 and 1.03 years in Period 2. Initial alloimmunization prevalence was lower in
      Period 2 (26.2%) versus Period 1 (37.5%) and after subsequent transfusions in
      Period 2 (23.8%) versus Period 1 (45.7%), although without significant difference
      after adjusting for number of units transfused, percentage of leukoreduced RBCs,
      sex, and age. Alloimmunized patients received more nonleukoreduced RBCs in Period
      1 than nonalloimmunized. Patients transfused during inflammatory conditions were
      not significantly more likely to become alloimmunized. CONCLUSIONS: The
      prevalence of initial and subsequent RBC alloimmunization in Period 2 was lower
      than that in Period 1; however, overall prevalence remained high. We recommend
      leukoreduced, hemoglobin S-negative Rh and Kell PAM RBCs for transfusion of
      patients with SCD. Component and recipient factors affecting alloimmunization
      should be studied further.

PMID- 29570816
TI  - Passive warming effect on soil microbial community and humic substance
      degradation in maritime Antarctic region.
AB  - Although the maritime Antarctic has undergone rapid warming, the effects on
      indigenous soil-inhabiting microorganisms are not well known. Passive warming
      experiments using open-top chamber (OTC) have been performed on the Fildes
      Peninsula in the maritime Antarctic since 2008. When the soil temperature was
      measured at a depth of 2-5 cm during the 2013-2015 summer seasons, the mean
      temperature inside OTC (OTC-In) increased by approximately 0.8  degrees C
      compared with outside OTC (OTC-Out), while soil chemical and physical
      characteristics did not change. Soils (2015 summer) from OTC-In and OTC-Out were
      subjected to analysis for change in microbial community and degradation rate of
      humic substances (HS, the largest pool of recalcitrant organic carbon in soil).
      Archaeal and bacterial communities in OTC-In were minimally affected by warming
      compared with those in OTC-Out, with archaeal methanogenic Thermoplasmata
      slightly increased in abundance. The abundance of heterotrophic fungi Ascomycota
      was significantly altered in OTC-In. Total bacterial and fungal biomass in OTC-In
      increased by 20% compared to OTC-Out, indicating that this may be due to
      increased microbial degradation activity for soil organic matter (SOM) including
      HS, which would result in the release of more low-molecular-weight growth
      substrates from SOM. Despite the effects of warming on the microbial community
      over the 8-years-experiments warming did not induce any detectable change in
      content or structure of polymeric HS. These results suggest that increased
      temperature may have significant and direct effects on soil microbial communities
      inhabiting maritime Antarctic and that soil microbes would subsequently provide
      more available carbon sources for other indigenous microbes.

PMID- 29570818
TI  - Identification of differentially expressed small RNAs and prediction of target
      genes in Italian Large White pigs with divergent backfat deposition.
AB  - The identification of the molecular mechanisms regulating pathways associated
      with the potential for fat deposition in pigs can lead to the detection of key
      genes and markers for the genetic improvement of fat traits. Interactions of
      microRNAs (miRNAs) with target RNAs regulate gene expression and modulate pathway
      activation in cells and tissues. In pigs, miRNA discovery is far from saturation,
      and the knowledge of miRNA expression in backfat tissue and particularly of the
      impact of miRNA variations is still fragmentary. Using RNA-seq, we characterized
      the small RNA (sRNA) expression profiles in Italian Large White pig backfat
      tissue. Comparing two groups of pigs divergent for backfat deposition, we
      detected 31 significant differentially expressed (DE) sRNAs: 14 up-regulated
      (including ssc-miR-132, ssc-miR-146b, ssc-miR-221-5p, ssc-miR-365-5p and the
      moRNA ssc-moR-21-5p) and 17 down-regulated (including ssc-miR-136, ssc-miR-195,
      ssc-miR-199a-5p and ssc-miR-335). To understand the biological impact of the
      observed miRNA expression variations, we used the expression correlation of DE
      miRNA target transcripts expressed in the same samples to define a regulatory
      network of 193 interactions between DE miRNAs and 40 DE target transcripts
      showing opposite expression profiles and being involved in specific pathways.
      Several miRNAs and mRNAs in the network were found to be expressed from backfat
      related pig QTL. These results are informative for the complex mechanisms
      influencing fat traits, shed light on a new aspect of the genetic regulation of
      fat deposition in pigs and facilitate the prospective implementation of
      innovative strategies of pig genetic improvement based on genomic markers.

PMID- 29570819
TI  - Hyperuricaemia and type 2 diabetes mellitus.
AB  - Choi et al reported the effect of hyperuricaemia on the new-onset type 2 diabetes
      mellitus (T2DM). I present three queries. (i) Insulin is considered to stimulate
      uric acid reabsorption via specific transporter and the effect of hyperuricaemia
      on the new-onset T2DM should be evaluated by considering insulin resistance. (ii)
      There is a limitation in the number of events for stable estimates. (iii) Obesity
      and sex should be considered for the analysis.

PMID- 29570820
TI  - Analysis of genetic relatedness among Indian cattle (Bos indicus) using
      genotyping-by-sequencing markers.
AB  - Genetic relatedness of 24 animals belonging to seven Indian cattle breeds was
      studied using high throughput genotyping-by-sequencing (GBS) markers. GBS
      produced 93.6 million reads with an average of about 3.9 million reads per
      animal. A total of 107 488 SNPs were identified in these individuals. When only
      one SNP per read was considered, a total of 60 261 SNPs representing independent
      reads were identified with an average SNP-to-SNP distance of 45 kb across the
      bovine reference genome. About 24% of the GBS-SNP markers were more than 100 kb
      apart. Of these, 58 322 SNPs mapped to autosomes, 1645 to the X chromosome and 28
      to the Y chromosome. The average SNP-to-SNP distance on the X chromosome was 91.3
      kb, whereas on the Y chromosome it was 1546.4 kb. The minor allele frequency
      within the Indian cattle varied from 0.103 (Ongole) to 0.177 (Siri), whereas
      Holstein cattle had the lowest value of 0.089. This is the first application of
      GBS in cattle of South Asia. The baseline information generated in this study
      might prompt implementation of GBS in breeding of cattle belonging to this
      region.

PMID- 29570821
TI  - Long-term cancer control outcomes in patients with biochemical recurrence and the
      impact of time from radical prostatectomy to biochemical recurrence.
AB  - BACKGROUND: Rates of metastatic progression (MP) and prostate cancer mortality
      (PCSM) are variable after biochemical recurrence (BCR) in patients who underwent
      radical prostatectomy (RP). To describe long-term oncological outcomes of BCR
      patients and to analyze risk factors for further outcomes in these men with a
      special focus on RP-BCR time. METHODS: We retrospectively analyzed the data of
      5509 RP patients treated between 1992 and 2006. Of those, we included 1321
      patients who experienced BCR (PSA level >=0.2 ng/mL) and did not receive any
      neoadjuvant or adjuvant therapy. Kaplan-Meier and time dependent Cox regression
      models were used. RESULTS: Median follow-up was 121 months. MP was recorded in
      177 (13.4%), PCSM in 126 (9.5%), and overall mortality (OM) in 264 (20.0%)
      patients. Patients with MP had worse tumor characteristics such as higher Gleason
      Scores (GS), rapid PSA doubling-time (DT), and shorter RP-BCR time intervals. MP
      free, PCSM-free, and overall survival rates were significantly worse in patients
      with RP-BCR time of <12 months versus patients with 12-35.9 or >=36 months (P <=
      0.001). Besides higher GS and rapid PSA-DT, RP-BCR time independently predicted
      MP, PCSM, and OM in multivariable regression analyses. Relative to the
      intermediate and longest RP-BCR time interval, the shortest interval (<12)
      carried the highest risk for all three endpoints. CONCLUSIONS: Only a small
      proportion of BCR patients proceed to MP or PCSM. Besides higher GS and rapid PSA
      DT a shorter RP-BCR interval (<12 months) heralds the most aggressive phenotype
      for progression to all three examined endpoints: MP, PCSM, and OM.

PMID- 29570822
TI  - Type 1 innate lymphoid cell aggravation of atherosclerosis is mediated through
      TLR4.
AB  - ILC populations elaborate a similar cytokine expression pattern with helper T
      cell subsets Th1, Th2 and Th17. Recent studies indicate that CD25+ILC2 could
      alleviate atherosclerosis by altering lipid metabolism, whereas the depletion of
      CD90-expressing ILCs had no influence on atherosclerosis. Thus, these findings
      raise the question of whether ILC1 cells react on atherosclerosis. Hence, our
      group attempted to explore the role of ILC1 cells in atherosclerosis. We found
      that ILC1 cells have a high Th1-like gene expression of T-bet and IFN-gamma,
      which is distinct from ILC2, ILC3 or conventional NK (cNK) cells. Moreover,
      atherosclerotic lesions were greatly reduced in ApoE-/-Rag1-/- mice treated with
      anti-NK1.1 mAbs for depleting ILC1 cells (ILC1+cNK cells), compared to ApoE-/
      Rag1-/- mice treated with anti-IL-15R mAbs for depleting cNK cells, and these
      effects could be fully rescued through the adoptive transfer of ILC1 cells sorted
      from the spleen of ApoE-/-TLR4+/+ mice into ApoE-/-Rag1-/- mice treated with anti
      NK1.1 mAbs. However, the adoptive transfer of ILC1 cells sorted from the spleen
      of ApoE-/-TLR4-/- mice into ApoE-/-Rag1-/- mice treated with anti-NK1.1 mAbs
      blocked the progression of atherosclerosis, indicating that the pro
      atherosclerotic role of ILC1 cells is dependent on TLR4. Furthermore, oxLDL
      induced increase in IFN-gamma expression from ApoE-/- ILC1 cells was correlated
      with the decrease in BACH2 expression. Taken together, ILC1 cells exist in
      atherosclerosis and aggravate atherosclerosis via increasing pro-inflammatory
      cytokine expression in a TLR4/BACH2-dependent manner.

PMID- 29570823
TI  - A pediatric case of squamous cell cancer in situ in the setting of
      sclerodermatous graft-versus-host disease and voriconazole treatment.
AB  - Sclerodermatous graft-versus-host disease is a subtype of cutaneous chronic graft
      versus-host disease that is characterized by sclerosis of the skin and
      subcutaneous tissue, resulting in debilitating contractures, among other life
      threatening complications. Children with sclerodermatous graft-versus-host
      disease are at high risk of developing nonmelanoma skin cancer because of several
      risk factors, including young age at transplantation, prolonged
      immunosuppression, and exposure to photosensitizing antimicrobial prophylaxis
      such as voriconazole. The immunosuppression required to treat sclerodermatous
      graft-versus-host disease makes effectively treating nonmelanoma skin cancer and
      sclerodermatous graft-versus-host disease in the same patient challenging. We
      describe a challenging case of a 6-year-old boy with a history of sclerodermatous
      graft-versus-host disease and voriconazole exposure presenting with squamous cell
      carcinoma in situ on the left temple and actinic keratoses on the scalp treated
      with topical chemotherapy agents.

PMID- 29570825
TI  - A Bayesian Analysis of Abundance, Trend, and Population Viability for Harbor
      Seals in Iliamna Lake, Alaska.
AB  - Harbor seals in Iliamna Lake, Alaska, are a small, isolated population, and one
      of only two freshwater populations of harbor seals in the world, yet little is
      known about their abundance or risk for extinction. Bayesian hierarchical models
      were used to estimate abundance and trend of this population. Observational
      models were developed from aerial survey and harvest data, and they included
      effects for time of year and time of day on survey counts. Underlying models of
      abundance and trend were based on a Leslie matrix model that used prior
      information on vital rates from the literature. We developed three scenarios for
      variability in the priors and used them as part of a sensitivity analysis. The
      models were fitted using Markov chain Monte Carlo methods. The population
      production rate implied by the vital rate estimates was about 5% per year, very
      similar to the average annual harvest rate. After a period of growth in the
      1980s, the population appears to be relatively stable at around 400 individuals.
      A population viability analysis assessing the risk of quasi-extinction, defined
      as any reduction to 50 animals or below in the next 100 years, ranged from 1% to
      3%, depending on the prior scenario. Although this is moderately low risk, it
      does not include genetic or catastrophic environmental events, which may have
      occurred to the population in the past, so our results should be applied
      cautiously.

PMID- 29570824
TI  - Adding new dimension to neuroscience.

PMID- 29570826
TI  - Explicating Experience: Development of a Valid Scale of Past Hazard Experience
      for Tornadoes.
AB  - People's past experiences with a hazard theoretically influence how they approach
      future risks. Yet, past hazard experience has been conceptualized and measured in
      wide-ranging, often simplistic, ways, resulting in mixed findings about its
      relationship with risk perception. This study develops a scale of past hazard
      experiences, in the context of tornadoes, that is content and construct valid. A
      conceptual definition was developed, a set of items were created to measure one's
      most memorable and multiple tornado experiences, and the measures were evaluated
      through two surveys of the public who reside in tornado-prone areas. Four
      dimensions emerged of people's most memorable experience, reflecting their
      awareness of the tornado risk that day, their personalization of the risk, the
      intrusive impacts on them personally, and impacts experienced vicariously through
      others. Two dimensions emerged of people's multiple experiences, reflecting
      common types of communication received and negative emotional responses. These
      six dimensions are novel in that they capture people's experience across the
      timeline of a hazard as well as intangible experiences that are both direct and
      indirect. The six tornado experience dimensions were correlated with tornado risk
      perceptions measured as cognitive-affective and as perceived probability of
      consequences. The varied experience-risk perception results suggest that it is
      important to understand the nuances of these concepts and their relationships.
      This study provides a foundation for future work to continue explicating past
      hazard experience, across different risk contexts, and for understanding its
      effect on risk assessment and responses.

PMID- 29570827
TI  - miR-376b-3p attenuates mitochondrial fission and cardiac hypertrophy by targeting
      mitochondrial fission factor.
AB  - Mitochondrial dysfunction contributes to the pathogenesis of cardiac hypertrophy.
      The disequilibrium of mitochondrial dynamic, which refers to mitochondrial fusion
      and fission, leads to mitochondrial morphology alteration and dysfunction.
      Enhanced understanding of the molecular mechanisms in depth may shed light on the
      therapy of the disease. In this study, we show that mitochondrial fission factor
      (MFF) is up-regulated upon hypertrophic agonist noradrenaline (NA) treatment.
      Knockdown of MFF attenuated NA induced mitochondrial fission and cardiac
      hypertrophy. Mitochondrial fission factor is a direct target of miR-376b-3p,
      which attenuated expression enhanced MFF expression through binding to its 3'UTR.
      Expression of miR-376b-3p weakened the fragmentation of mitochondria as well as
      decreased hypertrophic response through regulating MFF in NA treated neonatal rat
      ventricular cells (NRVCs). This study suggested that miR-376b-3p is a novel
      modulator affecting mitochondrial morphology through targeting MFF.

PMID- 29570828
TI  - Effect of the insect phenoloxidase on the metabolism of l-DOPA.
AB  - Insect prophenoloxidase (PPO) induces melanization around pathogens. Before
      melanization, PPO is cleaved into phenoloxidase (PO) by serine proteases. Insect
      PPO can also be activated by exogenous proteases secreted by pathogens as well as
      by other compounds, such as ethanol and cetylpyridinium chloride (CPC). However,
      the effect of these activators on the activity of PO is unclear. In this study,
      the insect endogenous serine protease AMM1, alpha-chymotrypsin, and ethanol were
      used to activate recombinant Drosophila PPO1 (rPPO1), and the PO activity
      differed depending on the activator applied. The PO-induced intermediates during
      melanization also varied markedly in their numbers and abundances. Therefore,
      this study indicates that the mechanism of PPO activation influences PO activity.
      It also suggests that PO-induced different intermediates may affect the
      antibacterial activity during melanization due to their toxicity.

PMID- 29570829
TI  - Gonadal histology of box jellyfish (Cnidaria: Cubozoa) reveals variation between
      internal fertilizing species Alatina alata (Alatinidae) and Copula sivickisi
      (Tripedaliidae).
AB  - Cubozoans (box jellyfish) are gonochoristic cnidarians with distinct reproductive
      strategies. This comparative histological study examines the gonad organization
      of Alatina alata and Copula sivickisi, two box jellyfish species that exhibit
      different modes of internal fertilization. A. alata reproduces via spermcasting
      aggregations while C. sivickisi reproduces via copulation; in both cases,
      internal fertilization occurs in the gastrovascular cavity. Herein, we provide
      the first histological description of subgastric sacs-structures unique to C.
      sivickisi. Although previously thought to function as sperm storage sacs, our
      findings reveal that subgastric sacs are nematocyst nests lacking sperm entirely.
      Conversely, we discovered that velarial spots in C. sivickisi females correspond
      to actual sperm storage structures. Histological examination of cubozoan sperm
      packages revealed that while sperm packages from both species have motile
      flagella, A. alata males produce nonencapsulated sperm bundles (i.e.,
      "spermatozeugmata"), and C. sivickisi males produce encapsulated packages (i.e.,
      "spermatophores"). Our findings corroborate the presence of several types of
      nematocysts in C. sivickisi embryo strands and spermatophores, and indicate their
      provenance to be both female and male gonads respectively, as well as subgastric
      sacs (i.e., nematocyst nests). In contrast to our findings of velarial spots as
      sperm storages structures in C. sivickisi females, and of nematocysts in the
      gonads of both sexes, we report that A. alata medusae lack both sperm storage
      structures and gonadal nematocysts. Finally, we discuss our findings on
      reproductive morphology of C. sivickisi and A. alata in light of the respective
      reproductive behavior of these two cubozoan species.

PMID- 29570830
TI  - Familial Blau syndrome without uveitis caused by a novel mutation in the
      nucleotide-binding oligomerization domain-containing protein 2 gene with good
      response to infliximab.
AB  - The proband in this study was a 4-year-old Mexican girl with Blau syndrome. She
      and her affected family members had skin rash and arthritis but no uveitis. Exome
      sequencing and DNA direct sequencing from blood samples revealed a novel
      nucleotide-binding oligomerization domain-containing protein 2 gene mutation in
      the affected family members. This study is the first report of a Mexican family
      with Blau syndrome showing good infliximab treatment response. The novel mutation
      in the nucleotide-binding oligomerization domain-containing protein 2 gene
      (c.1808A>G) enriches the mutation spectrum in Blau syndrome. This family
      represents one of the few cases of autosomal Blau syndrome with no uveitis;
      because of phenotype variability, it is important to recognize Blau syndrome's
      clinical spectrum and recommend genetic consultation.

PMID- 29570831
TI  - Combinations of Simple Mechanisms Explain Diverse Strategies in the Freehand
      Writing of Memorized Sentences.
AB  - Individual differences in the strategies that control sequential behavior were
      investigated in an experiment in which participants memorized sentences and then
      wrote them by hand, in a non-cursive style. Thirty-two participants each wrote
      eight sentences, which had hierarchical structures with five levels. The dataset
      included over 31,000 letters. Despite the deliberately constrained nature of the
      task and stimuli, 23 patterns of behavior were identified from the durations of
      pauses that occurred before the inscription of letters at four chunk levels,
      spanning letters, words, phrases, and sentences. A critical path task analytic
      model, Graphical Production of Memorized Sentences (GPoMS), shows that the
      control of writing relies on cues that continuously switch between motor actions
      and chunk retrievals in a just-in-time fashion at the level of letter
      information. GPoMS explains the individual differences in terms of variants of a
      motor production mechanism and variants of a chunk retrieval mechanism, which
      involve varying degrees of parallelism between cognitive actions and motor
      actions. A graphical technique for constructing GPoMS models was developed that
      enabled the estimation of ongoing working memory demands during production.

PMID- 29570832
TI  - Development of Mimokines, chemokine N terminus-based CXCR4 inhibitors optimized
      by phage display and rational design.
AB  - The chemokine receptor CXCR4 (C-X-C chemokine receptor type 4 also known as fusin
      or CD184 (cluster of differentiation 184)) is implicated in various biological
      and pathological processes of the hematopoietic and immune systems. CXCR4 is also
      one of the major coreceptors for HIV-1 entry into target cells and is
      overexpressed in many cancers, supporting cell survival, proliferation, and
      migration. CXCR4 is thus an extremely relevant drug target. Among the different
      strategies to block CXCR4, chemokine-derived peptide inhibitors hold great
      therapeutic potential. In this study, we used the N-terminus of vCCL2/vMIPII, a
      viral CXCR4 antagonist chemokine, as a scaffold motif to engineer and select
      CXCR4 peptide inhibitors, called Mimokines, which imitate the chemokine-binding
      mode but display an enhanced receptor affinity, antiviral properties, and
      receptor selectivity. We first engineered a Mimokine phage displayed library
      based on the first 21 residues of vCCL2, in which cysteine 11 and 12 were fully
      randomized and screened it against purified CXCR4 stabilized in liposomes. We
      identified Mimokines displaying up to 4-fold higher affinity for CXCR4 when
      compared to the reference peptide and fully protected MT-4 cells against HIV-1
      infection. These selected Mimokines were then subjected to dimerization, D-amino
      acid, and aza-beta3-amino acid substitution to further enhance their potency and
      selectivity. Optimized Mimokines exhibited up to 120-fold enhanced CXCR4 binding
      (range of 20 nM) and more than 200-fold improved antiviral properties (<= 1 MUM)
      compared to the parental Mimokines. Interestingly, these optimized Mimokines also
      showed up to 25-fold weaker affinity for ACKR3/CXCR7 and may therefore serve as
      lead compounds for further development of more selective CXCR4 peptide inhibitors
      and probes.

PMID- 29570833
TI  - Online Information Sharing About Risks: The Case of Organic Food.
AB  - Individuals have to make sense of an abundance of information to decide whether
      or not to purchase certain food products. One of the means to sense-making is
      information sharing. This article reports on a quantitative study examining
      online information sharing behavior regarding the risks of organic food products.
      An online survey among 535 respondents was conducted in the Netherlands to
      examine the determinants of information sharing behavior, and their
      relationships. Structural equation modeling was applied to test both the
      measurement model and the structural model. Results showed that the intention to
      share information online about the risks of organic food was low. Conversations
      and email were the preferred channels to share information; of the social media
      Facebook stood out. The developed model was found to provide an adequate
      description of the data. It explained 41% of the variance in information sharing.
      Injunctive norms and outcome expectancies were most important in predicting
      online information sharing, followed by information-related determinants. Risk
      perception-related determinants showed a significant, but weak, positive
      relationship with online information sharing. Implications for authorities
      communicating on risks associated with food are addressed.

PMID- 29570834
TI  - Successful treatment of severe subacute cutaneous lupus erythematosus with
      rituximab in an adolescent.
AB  - Subacute cutaneous lupus erythematosus is rare in children. Most patients respond
      well to conventional therapy with prednisone, hydroxychloroquine, or both. Other
      case reports and small series have reported successful clearance with rituximab
      in adults. We report an adolescent who obtained remission with rituximab after
      failing conventional therapy.

PMID- 29570835
TI  - Influence of diabetes on tissue healing in orthopaedic injuries.
AB  - Diabetes is a group of metabolic diseases characterized by hyperglycaemia
      resulting from the defective action or secretion of insulin. Chronic
      hyperglycaemia can lead to the damage, dysfunction and failure of various organs.
      In the context of complications of healing and orthopaedic rehabilitation,
      vascular (microangiopathy) and nerve (neuropathy) disorders deserve particular
      attention. About 12% of the patients admitted to orthopaedic departments have
      diabetes. Studies indicate that there is an indisputable link between diabetes
      and: an increased risk of fractures, the difficult healing of injuries of bones,
      ligaments and musculotendinous. It appears that one of the main reasons for this
      is non-enzymatic glycosylation (glycation) of collagen molecules, a phenomenon
      observed in the elderly and diabetic populations, as it leads to the formation of
      advanced glycation end products (AGEs). Collagen is one of the major connective
      tissue components, and is therefore part of ligaments, tendons and bones. AGEs
      affect the weakening of its structure and biomechanical properties, and thus also
      affects the weakening of the structure and properties of the above-mentioned
      tissues. The aim of the study is to undertake an overview of the current
      knowledge of the impact of diabetes on the risk of some injuries and subsequent
      healing and rehabilitation of patients following orthopaedic injuries.

PMID- 29570837
TI  - Due Process in Dual Process: Model-Recovery Simulations of Decision-Bound
      Strategy Analysis in Category Learning.
AB  - Behavioral evidence for the COVIS dual-process model of category learning has
      been widely reported in over a hundred publications (Ashby & Valentin, ). It is
      generally accepted that the validity of such evidence depends on the accurate
      identification of individual participants' categorization strategies, a task that
      usually falls to Decision Bound analysis (Maddox & Ashby, ). Here, we examine the
      accuracy of this analysis in a series of model-recovery simulations. In
      Simulation 1, over a third of simulated participants using an Explicit
      (conjunctive) strategy were misidentified as using a Procedural strategy. In
      Simulation 2, nearly all simulated participants using a Procedural strategy were
      misidentified as using an Explicit strategy. In Simulation 3, we re-examined a
      recently reported COVIS-supporting dissociation (Smith et al., ) and found that
      these misidentification errors permit an alternative, single-process, explanation
      of the results. Implications for due process in the future evaluation of dual
      process theories, including recommendations for future practice, are discussed.

PMID- 29570836
TI  - Spatial Vulnerability of Network Systems under Spatially Local Hazards.
AB  - A hazard is often spatially local in a network system, but its impact can spread
      out through network topology and become global. To qualitatively and
      quantitatively assess the impact of spatially local hazards on network systems,
      this article develops a new spatial vulnerability model by taking into account
      hazard location, area covered by hazard, and impact of hazard (including direct
      impact and indirect impact), and proposes an absolute spatial vulnerability index
      (ASVI) and a relative spatial vulnerability index (RSVI). The relationship
      between the new model and some relevant traditional network properties is also
      analyzed. A case study on the spatial vulnerability of the Chinese civil aviation
      network system is conducted to demonstrate the effectiveness of the model, and
      another case study on the Beijing subway network system to verify its
      relationship with traditional network properties.

PMID- 29570838
TI  - Frog tendon structure and its relationship with locomotor modes.
AB  - Tendon collagen fibrils are the basic force-transmitting units of the tendon.
      Yet, surprisingly little is known about the diversity in tendon anatomy and
      ultrastructure, and the possible relationships between this diversity and
      locomotor modes utilized. Our main objectives were to investigate: (a) the ultra
      structural anatomy of the tendons in the digits of frogs; (b) the diversity of
      collagen fibril diameters across frogs with different locomotor modes; (c) the
      relationship between morphology, as expressed by the morphology of collagen
      fibrils and tendons, and locomotor modes. To assess the relationship between
      morphology and the locomotor modes of the sampled taxa we performed a principal
      component analysis considering body length, fibrillar cross sectional area (CSA)
      and tendon CSA. A MANOVA showed that differences between species with different
      locomotor modes were significant with collagen fibril diameter being the
      discriminating factor. Overall, our data related the greatest collagen fibril
      diameter to the most demanding locomotor modes, conversely, the smallest collagen
      fibril CSA and the highest tendon CSA were observed in animals showing a hopping
      locomotion requiring likely little absorption of landing forces given the short
      jump distances.

PMID- 29570841
TI  - Selection of reference genes for tissue/organ samples on day 3 fifth-instar
      larvae in silkworm, Bombyx mori.
AB  - The silkworm, Bombyx mori, is one of the world's most economically important
      insect. Surveying variations in gene expression among multiple tissue/organ
      samples will provide clues for gene function assignments and will be helpful for
      identifying genes related to economic traits or specific cellular processes. To
      ensure their accuracy, commonly used gene expression quantification methods
      require a set of stable reference genes for data normalization. In this study, 24
      candidate reference genes were assessed in 10 tissue/organ samples of day 3 fifth
      instar B. mori larvae using geNorm and NormFinder. The results revealed that,
      using the combination of the expression of BGIBMGA003186 and BGIBMGA008209 was
      the optimum choice for normalizing the expression data of the B. mori
      tissue/organ samples. The most stable gene, BGIBMGA003186, is recommended if just
      one reference gene is used. Moreover, the commonly used reference gene encoding
      cytoplasmic actin was the least appropriate reference gene of the samples
      investigated. The reliability of the selected reference genes was further
      confirmed by evaluating the expression profiles of two cathepsin genes. Our
      results may be useful for future studies involving the quantification of relative
      gene expression levels of different tissue/organ samples in B. mori.

PMID- 29570840
TI  - Olfactory reference syndrome: a patient's perspective.

PMID- 29570842
TI  - Understanding the new tremor classification.

PMID- 29570839
TI  - Transglutaminase 2: Friend or foe? The discordant role in neurons and astrocytes.
AB  - Members of the transglutaminase family catalyze the formation of isopeptide bonds
      between a polypeptide-bound glutamine and a low molecular weight amine (e.g.,
      spermidine) or the E-amino group of a polypeptide-bound lysine. Transglutaminase
      2 (TG2), a prominent member of this family, is unique because in addition to
      being a transamidating enzyme, it exhibits numerous other activities. As a
      result, TG2 plays a role in many physiological processes, and its function is
      highly cell type specific and relies upon a number of factors, including
      conformation, cellular compartment location, and local concentrations of Ca2+ and
      guanine nucleotides. TG2 is the most abundant transglutaminase in the central
      nervous system (CNS) and plays a pivotal role in the CNS injury response. How TG2
      affects the cell in response to an insult is strikingly different in astrocytes
      and neurons. In neurons, TG2 supports survival. Overexpression of TG2 in primary
      neurons protects against oxygen and glucose deprivation (OGD)-induced cell death
      and in vivo results in a reduction in infarct volume subsequent to a stroke.
      Knockdown of TG2 in primary neurons results in a loss of viability. In contrast,
      deletion of TG2 from astrocytes results in increased survival following OGD and
      improved ability to protect neurons from injury. Here, a brief overview of TG2 is
      provided, followed by a discussion of the role of TG2 in transcriptional
      regulation, cellular dynamics, and cell death. The differing roles TG2 plays in
      neurons and astrocytes are highlighted and compared to how TG2 functions in other
      cell types.

PMID- 29570843
TI  - Molecular changes in the absence of severe pathology in the pulvinar in dementia
      with Lewy bodies.
AB  - BACKGROUND: Dementia with Lewy bodies is characterized by transient clinical
      features, including fluctuating cognition and visual hallucinations, implicating
      dysfunction of cerebral hub regions, such as the pulvinar nuclei of the thalamus.
      However, the pulvinar is typically only mildly affected by Lewy body pathology in
      dementia with Lewy bodies, suggesting additional factors may account for its
      proposed dysfunction. METHODS: We conducted a comprehensive analysis of
      postmortem pulvinar tissue using whole-transcriptome RNA sequencing, protein
      expression analysis, and histological evaluation. RESULTS: We identified 321
      transcripts as significantly different between dementia with Lewy bodies cases
      and neurologically normal controls, with gene ontology pathway analysis
      suggesting the enrichment of transcripts related to synapses and positive
      regulation of immune functioning. At the protein level, proteins related to
      synaptic efficiency were decreased, and general synaptic markers remained intact.
      Analysis of glial subpopulations revealed astrogliosis without activated
      microglia, which was associated with synaptic changes but not neurodegenerative
      pathology. DISCUSSION: These results indicate that the pulvinar, a region with
      relatively low Lewy body pathological burden, manifests changes at the molecular
      level that differ from previous reports in a more severely affected region. We
      speculate that these alterations result from neurodegenerative changes in regions
      connected to the pulvinar and likely contribute to a variety of cognitive changes
      resulting from decreased cortical synchrony in dementia with Lewy bodies. (c)
      2018 International Parkinson and Movement Disorder Society.

PMID- 29570844
TI  - Maintenance of redox balance by antioxidants in hemolymph of the greater wax moth
      Galleria mellonella larvae during encapsulation response.
AB  - The lipid peroxidation process in hemocytes, activities of phenoloxidase and key
      enzymatic antioxidants (superoxide dismutase, glutathione-S-transferase,
      catalase) and nonenzymatic antioxidants (thiols, ascorbate) in hemolymph of the
      greater wax moth Galleria mellonella L. (Lepidoptera: Pyralidae) were studied
      during the encapsulation process of nylon implants. It has been established that
      as soon as 15 min after piercing a cuticle with the implant, a capsule is formed
      on its surface. Active melanization of the capsule has been shown to last for 4
      h. During the first hours after incorporating the implant, an increase in
      phenoloxidase activity and lipid peroxidation in the insect hemocytes has been
      revealed. Adhesion and degranulation on the surface of foreign object lead to the
      depletion of total hemocytes count (THC). Our results indicated that thiols and
      ascorbate molecules take part in the immediate antioxidant response, during later
      stages of encapsulation process hemolymph glutathione-S-transferase detoxifies
      and protects insect organism thereby restoring the internal redox balance. We
      suggest that nonenzymatic and enzymatic antioxidants of hemolymph plasma play a
      key role in the maintenance of redox balance during encapsulation of foreign
      targets.

PMID- 29570845
TI  - Melatonin and cardioprotection against ischaemia/reperfusion injury: What's new?
      A review.
AB  - Melatonin is a pleiotropic hormone with several functions. It binds to specific
      receptors and to a number of cytosolic proteins, activating a vast array of
      signalling pathways. Its potential to protect the heart against
      ischaemia/reperfusion damage has attracted much attention, particularly in view
      of its possible clinical applications. This review will focus mainly on the
      possible signalling pathways involved in melatonin-induced cardioprotection. In
      particular, the role of the melatonin receptors and events downstream of receptor
      activation, for example, the reperfusion injury salvage kinase (RISK), survivor
      activating factor enhancement (SAFE) and Notch pathways, the sirtuins, nuclear
      factor E2-related factor 2 (Nrf2) and translocases in the outer membrane (TOM70)
      will be discussed. Particular attention is given to the role of the mitochondrion
      in melatonin-induced cardioprotection. In addition, a brief overview will be
      given regarding the status quo of the clinical application of melatonin in
      humans.

PMID- 29570846
TI  - Neuroprotective Effects of Creatine in the CMVMJD135 Mouse Model of
      Spinocerebellar Ataxia Type 3.
AB  - BACKGROUND AND OBJECTIVE: Mitochondrial dysfunction has been implicated in
      several neurodegenerative diseases. Creatine administration increases
      concentration of the energy buffer phosphocreatine, exerting protective effects
      in the brain. We evaluate whether a creatine-enriched diet would be beneficial
      for a mouse model of spinocerebellar ataxia type 3, a genetically defined
      neurodegenerative disease for which no treatment is available. METHODS: We
      performed 2 independent preclinical trials using the CMVMJD135 mouse model
      (treating 2 groups of animals with different disease severity) and wild-type
      mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29
      (preclinical trial 2) weeks, starting at a presymptomatic age. Motor behavior was
      evaluated at several time points from 5 to 34 weeks of age, and neuropathological
      studies were performed at the end of each trial. RESULTS: Creatine
      supplementation led to an overall improvement in the motor phenotype of CMVMJD135
      mice in both trials, rescuing motor balance and coordination and also restored
      brain weight, mitigated astrogliosis, and preserved Calbindin-positive cells in
      the cerebellum. Moreover, a reduction of mutant ataxin-3 aggregates occurred
      despite maintained steady-state levels of the protein and the absence of
      autophagy activation. Creatine treatment also restored the expression of the
      mitochondrial mass marker Porin and reduced the expression of antioxidant enzymes
      Heme oxygenase 1 (HO1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), suggesting a
      beneficial effect at the level of mitochondria and oxidative stress. CONCLUSIONS:
      Creatine slows disease progression and improves motor dysfunction as well as
      ameliorates neuropathology of the CMVMJD135 animals, supporting this as a useful
      strategy to slow the progression of spinocerebellar ataxia type 3. (c) 2018
      International Parkinson and Movement Disorder Society.

PMID- 29570847
TI  - No evidence of iatrogenic human transmission in autopsy confirmed multiple system
      atrophy.

PMID- 29570848
TI  - Quality of Life in Huntington's Disease: Critique and Recommendations for
      Measures Assessing Patient Health-Related Quality of Life and Caregiver Quality
      of Life.
AB  - The compromise of quality of life in Huntington's disease is a major issue, both
      for individuals with the disease as well as for their caregivers. The
      International Parkinson and Movement Disorder Society commissioned a review of
      the use and clinimetric validation status of measures used in Huntington's
      disease to assess aspects related with quality of life and to make
      recommendations on their use following standardized criteria. We included both
      patient-centered measures (patient health-related quality-of-life measures) and
      caregiver-centered measures (caregiver quality-of-life measures). After
      conducting a systematic literature search, we included 12 measures of patient
      health-related quality of life and 2 measures of caregiver quality of life.
      Regarding patient-centered measures, the Medical Outcomes Study 36-Item Short
      Form Health Survey is "recommended" as a generic assessment of health-related
      quality of life in patients with Huntington's disease. The 12-Item Short Form
      Health Survey, the Sickness Impact Profile, the 12-item World Health Organization
      Disability Assessment Schedule, and the Huntington's Disease Health-Related
      Quality of Life questionnaire are "suggested." No caregiver-centered quality-of
      life measure obtained a "recommended" status. The Alzheimer's Carer's Quality of
      Life Inventory and the Huntington's Disease Quality of Life Battery for Carers
      are "suggested." Recognizing that the assessment of patient health-related
      quality of life can be challenging in Huntington's disease, as patients may lack
      insight and there is insufficient clinimetric testing of these scales, the
      committee concluded that further validation of currently available health-related
      quality-of-life measures should be undertaken, namely, those Huntington's disease
      specific health-related quality-of-life measures that have recently been reported
      and used. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 29570849
TI  - Usefulness of two- and three-dimensional transesophageal echocardiography in
      combined mitral valve-in-valve implantation and paraprosthetic leak closure.
AB  - We demonstrate the usefulness of two- and live/real time three-dimensional
      transesophageal echocardiography in a procedure, which combined transcatheter
      mitral valve-in-valve deployment and paraprosthetic leak closure in the same
      setting using the less invasive transfemoral approach in an adult patient with
      bioprosthetic mitral valve degeneration. We also highlight the additive value of
      three-dimensional echocardiography over the two-dimensional technique.

PMID- 29570850
TI  - Physician characteristics influence the trends in resuscitation decisions at
      different ages.
AB  - AIM: We examined how physicians in different medical specialties would evaluate
      treatment decisions for vulnerable patients in need of resuscitation. METHODS: A
      survey depicting six acutely ill patients from newborn infant to aged, all in
      need of resuscitation with similar prognoses, was distributed (in 2009) to a
      representative sample of 1650 members of the Norwegian Medical Association and
      676 members of the Norwegian Pediatric Association. RESULTS: There were 1335
      respondents (57% participation rate). The majority of respondents across all
      specialties thought resuscitation was in the best interest of a 24 weeks'
      gestation preterm infant and would resuscitate the patient, but would also accept
      palliative care on the family's demand. Accepting a family's refusal of
      resuscitation was more common for the newborn infants. Specialists were overall
      similar in their answers, but specialty, age and gender were associated with
      different answers for the patients at both ends of the age spectrum. CONCLUSION:
      Resuscitation decisions for the very young do not always seem to follow the best
      interest principle. Specialty and personal characteristics still have an impact
      on how we consider important ethical issues. We must be cognisant of our own
      valuations and how they may influence care.

PMID- 29570851
TI  - Stoned-A Syndrome of D-Lactic Acidosis and Urolithiasis.
AB  - Short bowel syndrome (SBS) can lead to many complications related to the
      condition and its therapy. We describe 2 children with SBS who we believe are the
      second and third patients documented to have experienced both D-lactic acidosis
      and urolithiasis. We review aspects of these SBS complications and recent
      findings on the microbiome of patients with SBS that may predispose to these
      complications.

PMID- 29570852
TI  - Age- and sex-related heterogeneity in prodromal Parkinson's disease.

PMID- 29570853
TI  - Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced
      Parkinson's disease.
AB  - BACKGROUND: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa
      enteral suspension in the United States) provides stable plasma levodopa
      concentrations and reduces motor fluctuations in advanced Parkinson's disease
      patients through continuous delivery of levodopa via percutaneous endoscopic
      gastrojejunostomy. We report long-term safety and efficacy outcomes from an open
      label phase 3 treatment program. METHODS: PD patients (n = 262) who completed a
      12-week double-blind study and its 52-week open-label extension or a separate 54
      week open-label study were enrolled in this ongoing phase 3 open-label,
      multinational study (NCT00660673). Safety and efficacy assessments were collected
      every 6 months. RESULTS: Mean total duration of exposure to levodopa-carbidopa
      intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall
      discontinuation rate was 34% (average annual discontinuation rate, 10%). Although
      most patients (94%) reported an adverse event, the rate of adverse events
      decreased over time; 53% experienced a serious adverse event. Of patients in this
      extension study, 54% required jejunal tube replacement during the study, and 37%
      required percutaneous endoscopic gastrostomy tube replacement. Most patients were
      on levodopa monotherapy. Patients maintained reductions in "off" time and
      increases in mean "on" time without dyskinesia from initial levodopa-carbidopa
      intestinal gel infusion to he study end point (P < 0.001; n = 81). Activities of
      daily living and quality-of-life assessments demonstrated significant
      improvements that persisted through the study. CONCLUSIONS: This long-term study
      demonstrates sustained and clinically meaningful benefits from levodopa-carbidopa
      intestinal gel in advanced PD patients. Although adverse event rates decreased
      over time, vigilance is required for device-related complications and adverse
      events. (c) 2018 The Authors. Movement Disorders published by Wiley Periodicals,
      Inc. on behalf of International Parkinson and Movement Disorder Society.

PMID- 29570854
TI  - Daily melatonin protects the endothelial lineage and functional integrity against
      the aging process, oxidative stress, and toxic environment and restores blood
      flow in critical limb ischemia area in mice.
AB  - We tested the hypothesis that daily melatonin treatment protects endothelial
      lineage and functional integrity against the aging process, oxidative
      stress/endothelial denudation (ED), and toxic environment and restored blood flow
      in murine critical limb ischemia (CLI). In vitro study using HUVECs, in vivo
      models (ie, CLI through left femoral artery ligation and ED through carotid
      artery wire injury), and model of lipopolysaccharide-induced aortic injury in
      young (3 months old) and aged (8 months old) mice were used to elucidate effects
      of melatonin treatment on vascular endothelial integrity. In vitro study showed
      that menadione-induced oxidative stress (NOX-1/NOX-2), inflammation (TNF-alpha/NF
      kB), apoptosis (cleaved caspase-3/PARP), and mitochondrial damage (cytosolic
      cytochrome c) in HUVECs were suppressed by melatonin but reversed by SIRT3-siRNA
      (all P < .001). In vivo, reduced numbers of circulating endothelial progenitor
      cells (EPCs) (C-kit/CD31+/Sca-1/KDR+/CXCR4/CD34+), and angiogenesis (Matrigel
      assay of bone marrow-derived EPC and ex vivo aortic ring cultures) in older
      (compared with younger) mice were significantly reversed through daily melatonin
      administration (20 mg/kg/d, ip) (all P < .001). Aortic vasorelaxation and nitric
      oxide release were impaired in older mice and reversed in age-match mice
      receiving melatonin (all P < .01). ED-induced intimal/medial hyperplasia, reduced
      blood flow to ischemic limb, and angiogenesis (reduced CD31+/vWF+ cells/small
      vessel number) were improved after daily melatonin treatment (all P < .0001).
      Lipopolysaccharide-induced aortic endothelial cell detachment, which was more
      severe in aged mice, was also alleviated after daily melatonin treatment (P <
      .0001). Daily melatonin treatment protected both structural and functional
      integrity of vascular endothelium against aging-, oxidative stress-,
      lipopolysaccharide-, and ischemia-induced damage probably through upregulating
      the SIRT signaling pathway.

PMID- 29570856
TI  - Health conditions and unmet needs for assistance to perform activities of daily
      living among older adults with dementia in Chile.
AB  - OBJECTIVE: This study aims to address gaps in health conditions and unmet needs
      in daily activities between people with dementia (PWD) and without dementia in a
      developing country and to identify the variables associated with unmet needs
      among PWD to guide practitioners and policymakers in dealing with an increased
      burden of dementia. METHODS: Nationally representative data on 4655 Chileans age
      60 and over were used to compare health conditions and unmet needs in daily life
      activities between individuals with (N = 455, 9.6%) and without dementia.
      Regression analysis was conducted to identify the variables associated with unmet
      needs among PWD. RESULTS: Overall, PWD had worse health and needed greater
      assistance in performing daily activities than people without dementia. Among
      PWD, being male was associated with more unmet needs, in both activities of daily
      living (ADL) and instrumental ADL. Lower educational level and fewer caregivers
      were associated with more unmet needs for ADL, while inferior functional ability
      was associated with more unmet needs for instrumental ADL. CONCLUSIONS: The
      results from this study call for action by practitioners and policymakers to
      foster caregiver training, increase supportive services, and advance care
      planning for PWD.

PMID- 29570855
TI  - Post-influenzal triazole-resistant aspergillosis following allogeneic stem cell
      transplantation.
AB  - Influenza virus infection is now recognised as a risk factor for invasive
      pulmonary aspergillosis (IPA). Delays in diagnosis contribute to delayed
      commencement of antifungal therapy. In addition, the emergence of resistance to
      first-line triazole antifungal agents puts emphasis on early detection to prevent
      adverse outcomes. We present 2 allogeneic stem cell transplant patients who
      developed IPA due to triazole-resistant Aspergillus fumigatus following influenza
      infection. We underline the challenges faced in the management of these cases,
      the importance of early diagnosis and need for surveillance given the emergence
      of triazole resistance.

PMID- 29570857
TI  - Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis
      in patients with renal impairment: Challenges and lessons of the VITAL trial.
AB  - Invasive fungal disease (IFD) confers a substantial risk for morbidity and
      mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most
      common IFD caused by moulds but the prevalence of other rare mould diseases, such
      as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing.
      Treatments are available for IA, but evidence to support efficacy and safety of
      antifungal agents for rare IFDs, or for IFDs in special patient populations, is
      limited or lacking. The VITAL trial was conducted to assess the efficacy and
      safety of isavuconazole for the treatment of patients with IA and renal
      impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These
      patients stand to benefit most from a new treatment option but are unlikely to be
      included in a randomised, controlled trial. In this article, we review the
      challenges faced in the design and conduct of the VITAL trial. We also review the
      findings of VITAL, which included evidence of the efficacy and safety of
      isavuconazole. Finally, we consider the importance of trials such as VITAL to
      inform therapeutic decision making for clinicians faced with the challenge of
      treating patients with rare IFDs and as one paradigm of how to determine efficacy
      and safety of new drugs for rare and resistant infections without a suitable
      comparator.

PMID- 29570858
TI  - Metabolic control of cell fate bifurcations in a hematopoietic progenitor
      population.
AB  - Growth signals drive hematopoietic progenitor cells to proliferate and branch
      into divergent cell fates, but how unequal outcomes arise from a common
      progenitor is not fully understood. We used steady-state analysis of in vivo
      hematopoiesis and Fms-related tyrosine kinase 3 ligand (Flt3L)-induced in vitro
      differentiation of dendritic cells (DCs) to determine how growth signals regulate
      lineage bias. We found that Flt3L signaling induced anabolic activation and
      proliferation of DC progenitors, which was associated with DC differentiation.
      Perturbation of processes associated with quiescence and catabolism, including
      AMP-activated protein kinase signaling, fatty acid oxidation, or mitochondrial
      clearance increased development of cDC2 cells at the expense of cDC1 cells.
      Conversely, scavenging anabolism-associated reactive oxygen species skewed
      differentiation toward cDC1 cells. Sibling daughter cells of dividing DC
      progenitors exhibited unequal expression of the transcription factor interferon
      regulatory factor 8, which correlated with clonal divergence in FoxO3a signaling
      and population-level bifurcation of cell fate. We propose that unequal
      transmission of growth signals during cell division might support fate branches
      during proliferative expansion of progenitors.

PMID- 29570859
TI  - Oral lorazepam can be substituted for intravenous midazolam when weaning
      paediatric intensive care patients off sedation.
AB  - AIM: Intravenous sedatives used in the paediatric intensive care unit (PICU) need
      to be tapered after prolonged use to prevent iatrogenic withdrawal syndrome
      (IWS). We evaluated the occurrence of IWS and the levels of sedation before and
      after conversion from intravenous midazolam to oral lorazepam. METHODS: This was
      a retrospective, observational, single cohort study of children under the age of
      18 admitted to the PICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam,
      The Netherlands, between January 2013 and December 2014. The outcome parameters
      were the Sophia Observation withdrawal Symptoms (SOS) scale scores and COMFORT
      Behaviour scale scores before and after conversion. RESULTS: Of the 79 patients
      who were weaned, 32 and 39 had before and after SOS scores and 77 had COMFORT-B
      scores. IWS was reported in 15 of 79 patients (19.0%) during the 48 hours before
      the start of lorazepam and 17 of 79 patients (21.5%) during the 48 hours after
      treatment started. Oversedation was seen in 16 of 79 patients (20.3%) during the
      24 hours before substitution and in 30 of 79 patients (38.0%) during the 24 hours
      after substitution. CONCLUSION: The weaning protocol was not able to prevent IWS
      in all patients, but converting from intravenous midazolam to oral lorazepam did
      not increase the incidence.

PMID- 29570860
TI  - Undifferentiated-type component mixed with differentiated-type early gastric
      cancer is a significant risk factor for endoscopic non-curative resection.
AB  - BACKGROUND AND AIM: Previous studies of surgical specimens have found that the
      presence of mixed histological components in differentiated-type early gastric
      cancer (EGC) is a risk factor for lymph node metastasis and indicates greater
      malignancy. As there have been no reports on its endoscopic treatment, we
      examined endoscopic curative resection in relation to differentiated-type
      predominant mixed-type (MT). METHODS: This was a single-center, retrospective
      study. Subjects were 2585 differentiated-type EGC in 2551 patients treated with
      endoscopic submucosal dissection (ESD) in our hospital between March 2005 and
      January 2016. These lesions comprised 2231 cases of curative resection and 354
      cases of non-curative resection. Histologically, 2339 lesions were pure
      differentiated-type (PDT) and 246 lesions were MT. Rates of curative resection
      were compared, according to tumor size, between different histological types.
      RESULTS: When curative and non-curative cases were compared using multivariate
      analysis among lesions measuring <=20 mm for factors other than those determining
      curative resection, significant differences were obtained for tumor diameter,
      ulcer, and MT. Among lesions measuring 21-30 mm, ulcer and MT were associated
      with significant differences. Among lesions measuring >30 mm, upper region and MT
      were associated with significant differences. Curative resection rates, in
      relation to histological type among lesions measuring <=20 mm, were 93.4% for PDT
      and 63.4% for MT, whereas corresponding rates were 85.1% and 60.0%, respectively,
      among lesions measuring 21-30 mm, and 55.3% and 30.2%, respectively, among
      lesions measuring >30 mm. CONCLUSION: We found that MT was a risk factor for non
      curative resection irrespective of lesion size.

PMID- 29570861
TI  - Standardized Competencies for Parenteral Nutrition Administration: The ASPEN
      Model.
AB  - Parenteral nutrition (PN) is a highly complex medication and its provision can be
      prone to a variety of errors. Safe administration of this therapy requires that
      the competency of clinicians, particularly nurses, be demonstrated using a
      standardized process. In this document, a standardized model for PN
      administration competency is proposed based on a competency framework, the ASPEN
      published interdisciplinary core competencies, discipline-specific standards of
      practice, safe practice recommendations, and clinical guidelines. ASPEN
      recognizes that all healthcare institutions may not currently meet the
      aspirational goals of this document. This framework will guide institutions and
      agencies in developing tools and procedures and maintaining competency of staff
      members around safe PN administration. The ASPEN Board of Directors has approved
      this document.

PMID- 29570862
TI  - Medical and surgical management of advanced Parkinson's disease.
AB  - Advanced Parkinson's disease is characterized by the presence of motor
      fluctuations, various degree of dyskinesia, and disability with functional impact
      on activities of daily living and independence. Therapeutic management aims to
      extend levodopa benefit while minimizing motor complications and includes, in
      selected cases, the implementation of drug infusion and surgical techniques. In
      milder forms of motor complications, these can often be controlled with
      manipulation of levodopa dose and the introduction of supplemental therapies such
      as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and
      dopamine agonists including apomorphine. Clinical experience and evidence from
      published studies indicate that when these agents cannot satisfactorily control
      motor complications, patients should be assessed and considered for device-aided
      therapies. This review article summarizes some of the newer available therapeutic
      opportunities such as use of enzyme inhibitors like opicapone and safinamide,
      adenosine A2A receptor antagonists, apomorphine and levodopa/carbidopa intestinal
      gel infusion, deep brain stimulation including the role of closed-loop and
      adaptive stimulation, and MRI-guided focused ultrasound. (c) 2018 International
      Parkinson and Movement Disorder Society.

PMID- 29570863
TI  - Current status of intra-operative graft assessment: Should it be the standard of
      care for coronary artery bypass graft surgery?
AB  - The "Achilles heel" of coronary artery bypass graft (CABG) surgery is graft
      patency. While long-term patency is determined by the type of conduit and the
      progression of graft and native vessel disease, short-term patency is affected by
      intra-operative technical issues. Transit-time flow measurements and epicardial
      ultrasound have been shown to accurately assess intra-operative graft patency.
      This review will examine the evidence to support the premise that intra-operative
      graft assessment is essential in determining graft patency and should be the
      standard of care when performing CABG surgery.

PMID- 29570864
TI  - A 21-Year Retrospective Study of the Toronto Western Hospital Deep Brain
      Stimulation Cohort.

PMID- 29570865
TI  - Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy in Parkinson
      Tremor: Reoperation After Benefit Decay.

PMID- 29570866
TI  - International Parkinson and movement disorder society evidence-based medicine
      review: Update on treatments for the motor symptoms of Parkinson's disease.
AB  - OBJECTIVE: The objective of this review was to update evidence-based medicine
      recommendations for treating motor symptoms of Parkinson's disease (PD).
      BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee
      recommendations for treatments of PD were first published in 2002 and updated in
      2011, and we continued the review to December 31, 2016. METHODS: Level I studies
      of interventions for motor symptoms were reviewed. Criteria for inclusion and
      quality scoring were as previously reported. Five clinical indications were
      considered, and conclusions regarding the implications for clinical practice are
      reported. RESULTS: A total of 143 new studies qualified. There are no clinically
      useful interventions to prevent/delay disease progression. For monotherapy of
      early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and
      rasagiline are clinically useful. For adjunct therapy in early/stable PD,
      nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For
      adjunct therapy in optimized PD for general or specific motor symptoms including
      gait, rivastigmine is possibly useful and physiotherapy is clinically useful;
      exercise-based movement strategy training and formalized patterned exercises are
      possibly useful. There are no new studies and no changes in the conclusions for
      the prevention/delay of motor complications. For treating motor fluctuations,
      most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal
      infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and
      bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine,
      clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS:
      The options for treating PD symptoms continues to expand. These recommendations
      allow the treating physician to determine which intervention to recommend to an
      individual patient. (c) 2018 International Parkinson and Movement Disorder
      Society.

PMID- 29570867
TI  - An Outbreak of Microsporum canis infection at a military base associated with
      stray cat exposure and person-to-person transmission.
AB  - Tinea corporis caused by Microsporum canis is usually associated with exposure to
      animals, but outbreaks with anthropophilic transmission were described. A large
      outbreak in a military base was investigated. We investigated the outbreak's
      source and risk factors for infection in order to contain and eliminate it. All
      staff-members at the base were interviewed and examined. A case-control analysis
      of symptomatic patients was used to elucidate risk factors. Stray cats were
      captured and sampled. M. canis isolated from skin and fur specimens of patients
      and cats were genotyped by microsatellite sequencing. Fifty-three of 502 staff
      members were symptomatic. Logistic regression showed risk associated with female
      gender, cat contact at base and performance of guarding duty. Multiple stray cats
      were found at the base. M. canis isolates from 4 cats and 4 patients had an
      identical genotype, while 2 patients had different genotypes. We describe the
      largest M. canis outbreak reported until now. Epidemiological and phylogenetic
      tools were used to investigate the source of the outbreak. Multiple exposures to
      stray cats caused infection of mainly young female soldiers performing guarding
      duty. Other persons were infected by person-to-person transmission. These
      findings aided in the termination of the outbreak.

PMID- 29570868
TI  - Chronic-active antibody-mediated rejection with or without donor-specific
      antibodies has similar histomorphology and clinical outcome - a retrospective
      study.
AB  - Chronic-active antibody-mediated rejection (c-aABMR) is defined as histological
      evidence of chronic endothelial injury (cg), also known as transplant
      glomerulopathy, and either microvascular inflammation (MVI) or positivity for
      C4d. Importantly, the presence of donor-specific antibodies (DSA) is currently
      still mandatory for the diagnosis of c-aABMR. This retrospective study of 41 c
      aABMR patients investigates whether cases suspicious for c-aABMR (DSA negative, n
      = 24) differ from cases of c-aABMR (DSA positive, n = 17) with respect to renal
      histology, allograft function and long-term graft survival. All included patients
      had progressive loss of allograft function and were diagnosed by for cause biopsy
      and scored according to the Banff '15 criteria. In all DSApos cases, DSA were de
      novo and the majority was directed against HLA-II being mostly anti-HLA-DQ
      antibodies. There were no statistically significant differences in clinical
      characteristics, decline in allograft function and renal allograft survival in
      cases with or without DSAs. All cases showed chronic histomorphological damage
      and inflammation, irrespective of the presence of DSA. Renal histology and
      clinical outcome of patients suspicious for c-aABMR (DSAneg) do not significantly
      differ from patients with a diagnosis of c-aABMR (DSApos). We believe that our
      study adds to the ongoing debate regarding the need for DSAs to be present for
      the diagnosis of c-aABMR.

PMID- 29570869
TI  - Fullerene-Based Materials as Hole-Transporting/Electron-Blocking Layers:
      Applications in Perovskite Solar Cells.
AB  - Here we report for the first time an efficient fullerene-based compound, FU7,
      able to act as hole-transporting material (HTM) and electron blocking contact. It
      has been applied on perovskite solar cells (PSCs), obtaining 0.81 times the
      efficiency of PSCs with the standard HTM, spiro-OMeTAD, with the additional
      advantage that this performance is reached without any additive introduced in the
      HTM layer. Moreover, as a proof of concept, we have described for the first time
      efficient PSCs in which both selective contacts are fullerene derivatives, to
      obtain unprecedented "fullerene sandwich" PSCs.

PMID- 29570870
TI  - On the Antibacterial Activity of Azacarboxylate Ligands: Lowered Metal Ion
      Affinities for Bis-amide Derivatives of EDTA do not mean Reduced Activity.
AB  - EDTA is widely used as an inhibitor of bacterial growth, affecting the uptake and
      control of metal ions by microorganisms. We describe the synthesis and
      characterisation of two symmetrical bis-amide derivatives of EDTA, featuring
      glycyl or pyridyl substituents: AmGly2 and AmPy2 . Metal ion affinities (logK)
      have been evaluated for a range of metals (Mg2+ , Ca2+ , Fe3+ , Mn2+ , Zn2+ ),
      revealing less avid binding compared to EDTA. The solid-state structures of
      AmGly2 and of its Mg2+ complex have been determined crystallographically. The
      latter shows an unusual 7-coordinate, capped octahedral Mg2+ centre. The
      antibacterial activities of the two ligands and of EDTA have been evaluated
      against a range of health-relevant bacterial species, three Gram negative
      (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) and a Gram
      positive (Staphylococcus aureus). The AmPy2 ligand is the only one that displays
      a significant inhibitory effect against K. pneumoniae, but is less effective
      against the other organisms. AmGly2 exhibits a more powerful inhibitory effect
      against E. coli at lower concentrations than EDTA (<3 mm) or AmPy2 , but loses
      its efficacy at higher concentrations. The growth inhibition of EDTA and AmGly2
      on mutant E. coli strains with defects in outer-membrane lipopolysaccharide (LPS)
      structures has been assessed to provide insight into the unexpected behaviour.
      Taken together, the results contradict the assumption of a simple link between
      metal ion affinity and antimicrobial efficacy.

PMID- 29570871
TI  - Water Splitting on Rutile TiO2 -Based Photocatalysts.
AB  - Water splitting using a semiconductor photocatalyst with sunlight has long been
      viewed as a potential means of large-scale H2 production from renewable
      resources. Different from anatase TiO2 , rutile enables preferential water
      oxidation, which is useful for the construction of a Z-scheme water-splitting
      system. The combination of rutile TiO2 with a suitable H2 -evolution
      photocatalyst such as a Pt-loaded BaZrO3 -BaTaO2 N solid solution enables solar
      driven water splitting into H2 and O2 . While rutile TiO2 is a wide-gap
      semiconductor with a bandgap of 3.0 eV, co-doping of rutile TiO2 with certain
      metal ions and/or nitrogen produces visible-light-driven photocatalysts, which
      are also useful as a component for water oxidation in visible-light-driven Z
      scheme water splitting. The key to achieving highly efficient water oxidation is
      to maintain a charge balance of dopants in the rutile, because single doping
      typically produces trap states that capture photogenerated electrons and/or
      holes. Here we provide a concise summary of rutile TiO2 -based photocatalysts for
      water-splitting systems.

PMID- 29570872
TI  - Bifunctional Squaramide Organocatalysts for the Asymmetric Addition of
      Formaldehyde tert-Butylhydrazone to Simple Aldehydes.
AB  - The nucleophilic addition of formaldehyde tert-butylhydrazone to simple aldehydes
      (a formal hetero-carbonyl-ene reaction) can be performed with good reactivity and
      excellent enantioselectivity by virtue of the dual hydrogen-bonding activation
      exerted by amide-squaramide organocatalysts. The resulting hydroxydiazenes (azo
      alcohols) were isolated in high yields as enantiomerically enriched azoxy
      compounds after a regioselective azo-to-azoxy transformation. Subsequent
      derivatization provides an entry to relevant amino alcohols, oxazolidinones, and
      derivatives thereof.

PMID- 29570873
TI  - Genomic adaptation of flowering-time genes during the expansion of rice
      cultivation area.
AB  - The diversification of flowering time in response to natural environments is
      critical for the spread of crops to diverse geographic regions. In contrast with
      recent advances in understanding the molecular basis of photoperiodic flowering
      in rice (Oryza sativa), little is known about how flowering-time diversification
      is structured within rice subspecies. By analyzing genome sequencing data and a
      set of 429 chromosome segment substitution lines (CSSLs) originating from 10
      diverse rice accessions with wide distributions, we revealed diverse effects of
      allelic variations for common flowering-time quantitative trait loci in the
      recipient's background. Although functional variations associated with a few loci
      corresponded to standing variations among subspecies, the identified functional
      nucleotide polymorphisms occurred recently after rice subgroup differentiation,
      indicating that the functional diversity of flowering-time gene sequences was not
      particularly associated with phylogenetic relationship between rice subspecies.
      Intensive analysis of the Hd1 genomic region identified the signature of an early
      introgression of the Hd1 with key mutation(s) in aus and temperate japonica
      accessions. Our data suggested that, after such key introgressions, new mutations
      were selected and accelerated the flowering-time diversity within subspecies
      during the expansion of rice cultivation area. This finding may imply that new
      genome-wide changes for flowering-time adaptation are one of the critical
      determinants for establishing genomic architecture of local rice subgroups. In
      depth analyses of various rice genomes coupling with the genetically confirmed
      phenotypic changes in a large set of CSSLs enabled us to demonstrate how rice
      genome dynamics has coordinated with the adaptation of cultivated rice during the
      expansion of cultivation area.

PMID- 29570875
TI  - Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of
      synaptic transmission in the mouse prefrontal cortex.
AB  - Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D1 - and D2 
      like receptors, which are pharmacologically exploited to manage neuropsychiatric
      conditions. Adenosine A2A receptors (A2A R) also control PFC-related responses
      and A2A R antagonists are potential anti-psychotic drugs. As tight antagonistic
      A2A R-D2 R and synergistic A2A R-D1 R interactions occur in other brain regions,
      we now investigated the crosstalk between A2A R and D1 /D2 R controlling synaptic
      transmission between layers II/III and V in mouse PFC coronal slices. Dopamine
      decreased synaptic transmission, a presynaptic effect based on the parallel
      increase in paired-pulse responses. Dopamine inhibition was prevented by the D2 R
      like antagonist sulpiride but not by the D1 R antagonist SCH23390 and was
      mimicked by the D2 R agonist sumanirole, but not by the agonists of either D4 R
      (A-412997) or D3 R (PD128907). Dopamine inhibition was prevented by the A2A R
      antagonist, SCH58261, and attenuated in A2A R knockout mice. Accordingly, triple
      labelling immunocytochemistry experiments revealed the co-localization of A2A R
      and D2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of
      the PFC. This reported positive A2A R-D2 R interaction controlling PFC synaptic
      transmission provides a mechanistic justification for the anti-psychotic
      potential of A2A R antagonists.

PMID- 29570874
TI  - Synthesis of Artemisinin-Derived Dimers, Trimers and Dendrimers: Investigation of
      Their Antimalarial and Antiviral Activities Including Putative Mechanisms of
      Action.
AB  - Generation of dimers, trimers and dendrimers of bioactive compounds is an
      approach that has recently been developed for the discovery of new potent drug
      candidates. Herein, we present the synthesis of new artemisinin-derived dimers
      and dendrimers and investigate their action against malaria parasite Plasmodium
      falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was the most
      active compound (EC50 1.4 nm) in terms of antimalarial efficacy and was even more
      effective than the standard drugs dihydroartemisinin (EC50 2.4 nm), artesunic
      acid (EC50 8.9 nm) and chloroquine (EC50 9.8 nm). Trimer 4 stood out as the most
      active agent against HCMV in vitro replication and exerted an EC50 value of 0.026
      MUm, representing an even higher activity than the two reference drugs
      ganciclovir (EC50 2.60 MUm) and artesunic acid (EC50 5.41 MUm). In addition,
      artemisinin-derived dimer 13 and trimer 15 were for the first time both
      immobilized on TOYOPEARL AF-Amino-650M beads and used for mass spectrometry-based
      target identification experiments using total lysates of HCMV-infected primary
      human fibroblasts. Two major groups of novel target candidates, namely
      cytoskeletal and mitochondrial proteins were obtained. Two putatively compound
      binding viral proteins, namely major capsid protein (MCP) and envelope
      glycoprotein pUL132, which are both essential for HCMV replication, were
      identified.

PMID- 29570876
TI  - Electron-Deficient Bipyrrole Boomerangs: Bright Fluorophores Obtained via Double
      C-H Bond Activation.
AB  - PdII -mediated annulative double C-H activation is shown to efficiently convert
      1,n-dipyrrolylalkanes into extensively pi-conjugated bipyrroles not accessible by
      conventional oxidative coupling protocols. This approach is applicable to both
      electron-rich and electron-deficient systems, and has been further developed into
      tandem processes involving further cyclization of substituents or oxygenation of
      pyrrolic alpha-positions. The new bipyrrole intermediates show enhanced
      fluorescence as well as tunable optical properties controlled by the alignment of
      chromophore subunits. Photophysical data, including femtosecond transient
      absorptions, reveal solvent-induced intramolecular charge transfer in their
      excited states, dependent on the polarity of the medium.

PMID- 29570877
TI  - Host- and stage-dependent secretome of the arbuscular mycorrhizal fungus
      Rhizophagus irregularis.
AB  - Arbuscular mycorrhizal fungi form the most wide-spread endosymbiosis with plants.
      There is very little host specificity in this interaction, however host
      preferences as well as varying symbiotic efficiencies have been observed. We
      hypothesize that secreted proteins (SPs) may act as fungal effectors to control
      symbiotic efficiency in a host-dependent manner. Therefore, we studied whether
      arbuscular mycorrhizal (AM) fungi adjust their secretome in a host- and stage
      dependent manner to contribute to their extremely wide host range. We
      investigated the expression of SP-encoding genes of Rhizophagus irregularis in
      three evolutionary distantly related plant species, Medicago truncatula,
      Nicotiana benthamiana and Allium schoenoprasum. In addition we used laser
      microdissection in combination with RNA-seq to study SP expression at different
      stages of the interaction in Medicago. Our data indicate that most expressed SPs
      show roughly equal expression levels in the interaction with all three host
      plants. In addition, a subset shows significant differential expression depending
      on the host plant. Furthermore, SP expression is controlled locally in the hyphal
      network in response to host-dependent cues. Overall, this study presents a
      comprehensive analysis of the R. irregularis secretome, which now offers a solid
      basis to direct functional studies on the role of fungal SPs in AM symbiosis.

PMID- 29570878
TI  - Genetic diversity and evolution of reduced sulfur storage during domestication of
      maize.
AB  - The domestication of maize has spanned a period of over 9000 years, during which
      time its wild relative teosinte underwent natural and artificial selection. We
      hypothesize that environmental conditions could have played a major role in this
      process. One factor of environmental variation is soil composition, which
      includes sulfur availability. Sulfur is reduced during photosynthesis and is used
      to synthesize cysteine and methionine, which drive the accumulation of delta10
      (Zm00001d045937), delta18 (Zm00001d037436), beta15 (Zm00001d035760), gamma16
      (Zm00001d005793), gamma27 (Zm00001d020592), and gamma50 (Zm00001d020591) zeins,
      representing the zein2 fraction (z2) of storage proteins in maize seeds. In this
      study, polymorphisms and haplotypes were detected based on six z2 genes in 60
      maize and teosintes lines. Haplotypes were unevenly distributed, and abundant
      genetic diversity was found in teosintes. Polymorphism was highest in z2delta18,
      whereas for z2beta15 single nucleotide polymorphism (SNP) density and
      insertion/deletion (indel) abundance were the lowest, indicating differential
      roles in seed evolution. Indels showed a clustered distribution, and most of
      these derived from teosintes. The indels not only led to tandem repeat
      polymorphisms, but also to frameshift mutations, which could also be used as null
      variants. In addition, neutral evolutionary tests, phylogenetic analyses, and
      population structures indicated that z2delta10 and z2gamma50 had undergone
      natural selection. Indeed, a natural selection imprint could also be found with
      z2gamma27 and z2gamma16, whereas z2delta18 and z2beta15 tended to be under
      neutral evolution. These results suggested that genetic diversity and evolution
      of a subset of sulfur-rich zeins could be under environmental adaptation during
      maize domestication.

PMID- 29570879
TI  - The E3 ubiquitin ligase SP1-like 1 plays a positive role in peroxisome biogenesis
      in Arabidopsis.
AB  - Peroxisomes are dynamic organelles crucial for a variety of metabolic processes
      during the development of eukaryotic organisms, and are functionally linked to
      other subcellular organelles, such as mitochondria and chloroplasts. Peroxisomal
      matrix proteins are imported by peroxins (PEX proteins), yet the modulation of
      peroxin functions is poorly understood. We previously reported that, besides its
      known function in chloroplast protein import, the Arabidopsis E3 ubiquitin ligase
      SP1 (suppressor of ppi1 locus1) also targets to peroxisomes and mitochondria, and
      promotes the destabilization of the peroxisomal receptor-cargo docking complex
      components PEX13 and PEX14. Here we present evidence that in Arabidopsis, SP1's
      closest homolog SP1-like 1 (SPL1) plays an opposite role to SP1 in peroxisomes.
      In contrast to sp1, loss-of-function of SPL1 led to reduced peroxisomal beta
      oxidation activity, and enhanced the physiological and growth defects of pex14
      and pex13 mutants. Transient co-expression of SPL1 and SP1 promoted each other's
      destabilization. SPL1 reduced the ability of SP1 to induce PEX13 turnover, and it
      is the N-terminus of SP1 and SPL1 that determines whether the protein is able to
      promote PEX13 turnover. Finally, SPL1 showed prevalent targeting to mitochondria,
      but rather weak and partial localization to peroxisomes. Our data suggest that
      these two members of the same E3 protein family utilize distinct mechanisms to
      modulate peroxisome biogenesis, where SPL1 reduces the function of SP1. Plants
      and possibly other higher eukaryotes may employ this small family of E3 enzymes
      to differentially modulate the dynamics of several organelles essential to energy
      metabolism via the ubiquitin-proteasome system.

PMID- 29570880
TI  - Analysis of the functions of TaGW2 homoeologs in wheat grain weight and protein
      content traits.
AB  - GW2 is emerging as a key genetic determinant of grain weight in cereal crops; it
      has three homoeologs (TaGW2-A1, -B1 and -D1) in hexaploid common wheat (Triticum
      aestivum L.). Here, by analyzing the gene editing mutants that lack one (B1 or
      D1), two (B1 and D1) or all three (A1, B1 and D1) homoeologs of TaGW2, several
      insights are gained into the functions of TaGW2-B1 and -D1 in common wheat grain
      traits. First, both TaGW2-B1 and -D1 affect thousand-grain weight (TGW) by
      influencing grain width and length, but the effect conferred by TaGW2-B1 is
      stronger than that of TaGW2-D1. Second, there exists functional interaction
      between TaGW2 homoeologs because the TGW increase shown by a double mutant
      (lacking B1 and D1) was substantially larger than that of their single mutants.
      Third, both TaGW2-B1 and -D1 modulate cell number and length in the outer
      pericarp of developing grains, with TaGW2-B1 being more potent. Finally, TaGW2
      homoeologs also affect grain protein content as this parameter was generally
      increased in the mutants, especially in the lines lacking two or three
      homoeologs. Consistent with this finding, two wheat end-use quality-related
      parameters, flour protein content and gluten strength, were considerably elevated
      in the mutants. Collectively, our data shed light on functional difference
      between and additive interaction of TaGW2 homoeologs in the genetic control of
      grain weight and protein content traits in common wheat, which may accelerate
      further research on this important gene and its application in wheat improvement.

PMID- 29570881
TI  - Lotus japonicus NOOT-BOP-COCH-LIKE1 is essential for nodule, nectary, leaf and
      flower development.
AB  - The NOOT-BOP-COCH-LIKE (NBCL) genes are orthologs of Arabidopsis thaliana BLADE
      ON-PETIOLE1/2. The NBCLs are developmental regulators essential for plant
      shaping, mainly through the regulation of organ boundaries, the promotion of
      lateral organ differentiation and the acquisition of organ identity. In addition
      to their roles in leaf, stipule and flower development, NBCLs are required for
      maintaining the identity of indeterminate nitrogen-fixing nodules with persistent
      meristems in legumes. In legumes forming determinate nodules, without persistent
      meristem, the roles of NBCL genes are not known. We thus investigated the role of
      Lotus japonicus NOOT-BOP-COCH-LIKE1 (LjNBCL1) in determinate nodule identity and
      studied its functions in aerial organ development using LORE1 insertional mutants
      and RNA interference-mediated silencing approaches. In Lotus, LjNBCL1 is involved
      in leaf patterning and participates in the regulation of axillary outgrowth. Wild
      type Lotus leaves are composed of five leaflets and possess a pair of nectaries
      at the leaf axil. Legumes such as pea and Medicago have a pair of stipules,
      rather than nectaries, at the base of their leaves. In Ljnbcl1, nectary
      development is abolished, demonstrating that nectaries and stipules share a
      common evolutionary origin. In addition, ectopic roots arising from nodule
      vascular meristems and reorganization of the nodule vascular bundle vessels were
      observed on Ljnbcl1 nodules. This demonstrates that NBCL functions are conserved
      in both indeterminate and determinate nodules through the maintenance of nodule
      vascular bundle identity. In contrast to its role in floral patterning described
      in other plants, LjNBCL1 appears essential for the development of both secondary
      inflorescence meristem and floral meristem.

PMID- 29570882
TI  - T2 , T1rho and TRAFF4 detect early regenerative changes in mouse ischemic
      skeletal muscle.
AB  - The identification of areas with regenerative potential in ischemic tissues would
      allow the targeting of treatments supporting tissue recovery. The regeneration
      process involves the activation of several cellular and molecular responses which
      could be detected using magnetic resonance imaging (MRI). However, to date,
      magnetic resonance (MR) relaxation parameters have received little attention in
      the diagnosis and follow-up of limb ischemia. The purpose of this study was to
      evaluate the feasibility of different MRI relaxation and diffusion tensor imaging
      parameters in the detection of areas showing early signs of regeneration in
      ischemic mouse skeletal muscles. T2 and T1rho relaxation time constants, together
      with TRAFFn , T1 and diffusion tensor imaging, were evaluated to differentiate
      areas of regeneration in a mouse hind limb ischemia model before and 0, 1, 4, 7,
      14 and 30 days after ischemia. All the measured relaxation times were longer in
      the areas of early regeneration compared with normal muscle tissue. The
      relaxation times increased after ischemia in the ischemic muscles, reaching a
      maximum at 4-7 days after occlusion, coinciding with the appearance of early
      signs of regeneration. Fractional anisotropy decreased significantly (p < 0.05)
      on days 1-4, whereas mean diffusivity, lambda1 and lambda2 decreased later,
      starting at day 7 after ischemia compared with the pre-operational time point.
      The percentages of areas with different tissue morphologies were determined based
      on histological analysis of the ischemic muscle cross-sections, and correlations
      between the percentages obtained and different relaxation times were calculated.
      The highest correlation between relaxation times and histology was achieved with
      T2 , T1rho and TRAFF4 (R2 = 0.96, R2 = 0.92 and R2 = 0.84, respectively, p <
      0.01). Early regenerative changes were visible using T2 , T1rho and TRAFF4 MR
      relaxation time constants in skeletal muscle after ischemia. These markers could
      potentially be used for the identification of targets for therapies supporting
      muscle regeneration after ischemic injury.

PMID- 29570884
TI  - A Stereochemically Driven Supramolecular Polymerisation.
AB  - Anthracyclines self-assemble in water into dimers. In the presence of
      sufficiently high salt (NaCl) concentrations, solutions of the antibiotic
      doxorubicin, but not those of the closely related molecules daunomycin and
      epirubicin, turn into gels barely compatible with the presence of small
      oligomers. The use of spectroscopic, scattering, imaging and computational
      techniques, allowed light to be shed on the self-assembly process that triggered
      doxorubicin gelification. A complex picture emerged, with doxorubicin molecules
      assembled into long, highly chiral, supramolecular aggregates made of hundreds of
      units, showing redshifted fluorescence spectra, very short fluorescence lifetimes
      and small-angle X-ray scattering profiles compatible with long cylinders. The
      involvement of specific chemical groups and the need for a specific
      stereochemistry of the monomers in the formation of a hydrogen-bond network to
      stabilise the supramolecular aggregates was supported by molecular dynamics
      calculations. A salt-induced, temperature-dependent, cooperative nucleation
      elongation supramolecular polymerisation of the doxorubicin molecules is deduced.

PMID- 29570883
TI  - Novel functions of the Arabidopsis transcription factor TCP5 in petal development
      and ethylene biosynthesis.
AB  - The flowers of most dicotyledons have petals that, together with the sepals,
      initially protect the reproductive organs. Later during development petals are
      required to open the flower and to attract pollinators. This diverse set of
      functions demands tight temporal and spatial regulation of petal development. We
      studied the functioning of the Arabidopsis thaliana TCP5-like transcription
      factors (TFs) in petals. Overexpression of TCP5 in petal epidermal cells results
      in smaller petals, whereas tcp5 tcp13 tcp17 triple knockout lines have wider
      petals with an increased surface area. Comprehensive expression studies revealed
      effects of TCP5-like TFs on the expression of genes related to the cell cycle,
      growth regulation and organ growth. Additionally, the ethylene biosynthesis genes
      1-amino-cyclopropane-1-carboxylate (ACC) synthase 2 (ACS2) and ACC oxidase 2
      (ACO2) and several ETHYLENE RESPONSE FACTORS (ERFs) are found to be
      differentially expressed in TCP5 mutant and overexpression lines. Chromatin
      immunoprecipitation-quantitative PCR showed direct binding of TCP5 to the ACS2
      locus in vivo. Ethylene is known to influence cell elongation, and the petal
      phenotype of the tcp5 tcp13 tcp17 mutant could be complemented by treatment of
      the plants with an ethylene pathway inhibitor. Taken together, this reveals a
      novel role for TCP5-like TFs in the regulation of ethylene-mediated petal
      development and growth.

PMID- 29570885
TI  - Shoot phytochrome B modulates reactive oxygen species homeostasis in roots via
      abscisic acid signaling in Arabidopsis.
AB  - Underground roots normally reside in darkness. However, they are often exposed to
      ambient light that penetrates through cracks in the soil layers which can occur
      due to wind, heavy rain or temperature extremes. In response to light exposure,
      roots produce reactive oxygen species (ROS) which promote root growth. It is
      known that ROS-induced growth promotion facilitates rapid escape of the roots
      from non-natural light. Meanwhile, long-term exposure of the roots to light
      elicits a ROS burst, which causes oxidative damage to cellular components,
      necessitating that cellular levels of ROS should be tightly regulated in the
      roots. Here we demonstrate that the red/far-red light photoreceptor phytochrome B
      (phyB) stimulates the biosynthesis of abscisic acid (ABA) in the shoots, and
      notably the shoot-derived ABA signals induce a peroxidase-mediated ROS
      detoxification reaction in the roots. Accordingly, while ROS accumulate in the
      roots of the phyb mutant that exhibits reduced primary root growth in the light,
      such an accumulation of ROS did not occur in the dark-grown phyb roots that
      exhibited normal growth. These observations indicate that mobile shoot-to-root
      ABA signaling links shoot phyB-mediated light perception with root ROS
      homeostasis to help roots adapt to unfavorable light exposure. We propose that
      ABA-mediated shoot-to-root phyB signaling contributes to the synchronization of
      shoot and root growth for optimal propagation and performance in plants.

PMID- 29570886
TI  - Lysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid
      plaques in the human hippocampus.
AB  - Lysosomal vesicles around neuritic plaques are thought to drive Alzheimer's
      disease by providing ideal microenvironments for generation of amyloid-beta.
      Although lysosomal vesicles are present at every amyloid plaque in mouse models
      of Alzheimer's disease, the number of amyloid plaques that contain lysosomal
      vesicles in the human brain remains unknown. This study aimed to quantify
      lysosomal vesicles at amyloid plaques in the human hippocampus. Lysosome
      associated membrane protein 1 (LAMP1)-positive vesicles accumulated in both
      diffuse (Abeta42-positive/AT8-negative) and neuritic (Abeta42-positive/AT8
      positive) plaques in all regions were analysed. In contrast to mouse models of
      Alzheimer's disease, however, not all amyloid plaques accumulated LAMP1-positive
      lysosomal vesicles. Even at neuritic plaques, LAMP1 immunoreactivity was more
      abundant than phospho-tau (AT8). Further, lysosomal vesicles colocalised weakly
      with phospho-tau such that accumulation of lysosomal vesicles and phospho-tau
      appeared to be spatially distinct events that occurred within dystrophic
      neurites. This quantitative study shows that diffuse plaques, as well as neuritic
      plaques, contain LAMP1 immunoreactivity in the human hippocampus.

PMID- 29570887
TI  - Estimating B1+ in the breast at 7 T using a generic template.
AB  - Dynamic contrast-enhanced MRI is the workhorse of breast MRI, where the diagnosis
      of lesions is largely based on the enhancement curve shape. However, this curve
      shape is biased by RF transmit (B1+ ) field inhomogeneities. B1+ field
      information is required in order to correct these. The use of a generic, coil
      specific B1+ template is proposed and tested. Finite-difference time-domain
      simulations for B1+ were performed for healthy female volunteers with a wide
      range of breast anatomies. A generic B1+ template was constructed by averaging
      simulations based on four volunteers. Three-dimensional B1+ maps were acquired in
      15 other volunteers. Root mean square error (RMSE) metrics were calculated
      between individual simulations and the template, and between individual
      measurements and the template. The agreement between the proposed template
      approach and a B1+ mapping method was compared against the agreement between
      acquisition and reacquisition using the same mapping protocol. RMSE values (% of
      nominal flip angle) comparing individual simulations with the template were in
      the range 2.00-4.01%, with mean 2.68%. RMSE values comparing individual
      measurements with the template were in the range8.1-16%, with mean 11.7%. The
      agreement between the proposed template approach and a B1+ mapping method was
      only slightly worse than the agreement between two consecutive acquisitions using
      the same mapping protocol in one volunteer: the range of agreement increased from
      +/-16% of the nominal angle for repeated measurement to +/-22% for the B1+
      template. With local RF transmit coils, intersubject differences in B1+ fields of
      the breast are comparable to the accuracy of B1+ mapping methods, even at 7 T.
      Consequently, a single generic B1+ template suits subjects over a wide range of
      breast anatomies, eliminating the need for a time-consuming B1+ mapping protocol.

PMID- 29570888
TI  - Predictive value of unipolar and bipolar electrograms in idiopathic outflow tract
      ventricular arrhythmia mapping and ablation.
AB  - INTRODUCTION: Radiofrequency catheter ablation is an effective therapy for focal
      idiopathic outflow tract ventricular arrhythmia (OTVA). However, visual
      inspection of the unipolar electrogram (EGM) QS morphology is subjective with a
      poor specificity for predicting successful ablation sites. This study aims to
      evaluate the predictive value of unipolar and bipolar EGMs in OTVA mapping and
      ablation. METHODS AND RESULTS: Twenty-two patients scheduled for idiopathic OTVA
      ablation were prospectively enrolled. During the procedure, unipolar and bipolar
      EGMs were recorded simultaneously and visually inspected by the operator to
      identify their values for predicting arrhythmogenic sites. Quantitative features
      of the unipolar EGM including the ratio of amplitude of the first positive peak
      versus the nadir (R-ratio), the maximum descending slope (MaxSlope), and the time
      interval between the initial deflection point to the MaxSlope (D-Max) were
      calculated for each target site in offline analysis. EGMs from 100 sites were
      collected in 20 patients and analyzed. The bipolar reverse polarity
      characteristic was not as practical for identifying successful ablation site as
      the unipolar QS characteristic. Successful ablation sites demonstrated smaller R
      ratio and shorter D-Max than unsuccessful sites, but no significant difference in
      MaxSlope. A unipolar EGM-derived quantitative criterion provided significantly
      better specificity (0.70) than visual inspection (0.37) without compromising on
      the sensitivity (0.83 vs. 0.89). CONCLUSION: The bipolar reverse polarity
      characteristic was not a practical method for identifying target in idiopathic
      OTVA ablation. The unipolar EGM-derived quantitative criteria have better
      predictive performance than visual inspection of the QS characteristic and are
      likely to reduce unnecessary ablation sites.

PMID- 29570889
TI  - Enzyme-PISA: An Efficient Method for Preparing Well-Defined Polymer Nano-Objects
      under Mild Conditions.
AB  - Enzyme catalysis is a mild, efficient, and selective technique that has many
      applications in organic synthesis as well as polymer synthesis. Here, a novel
      enzyme-catalysis-induced reversible addition-fragmentation chain transfer (RAFT)
      mediated dispersion polymerization for preparing AB diblock copolymer nano
      objects with complex morphologies at room temperature is described. Taking
      advantage of the room-temperature feature, it is shown that pure, worm-like
      polymer nano-objects can be readily prepared by just monitoring the viscosity.
      Moreover, it is demonstrated that inorganic nanoparticles and proteins can be
      loaded in situ into vesicles by this method. Finally, a novel oxygen-tolerant
      RAFT-mediated dispersion polymerization initiated by enzyme cascade reaction that
      can be carried out in open vessels is developed. The enzyme-initiated RAFT
      dispersion polymerization provides a facile platform for the synthesis of various
      functional polymer nano-objects under mild conditions.

PMID- 29570890
TI  - Threats and Supports to Female Students' Math Beliefs and Achievement.
AB  - This study examines how student perceptions of teacher practices contribute to
      female high school students' math beliefs and achievement. Guided by the
      expectancy-value framework, we hypothesized that students' motivation beliefs and
      achievement outcomes in mathematics are fostered by teachers' emphasis on the
      relevance of mathematics and constrained by gender-based differential treatment.
      To examine these questions, structural equation modeling was applied to a
      longitudinal panel of 518 female students from the Maryland Adolescent
      Development in Context Study. While controlling for prior achievement and race,
      gendered differential treatment was negatively associated with math beliefs and
      achievement, whereas relevant math instruction was positively associated with
      these outcomes. These findings suggest inroads that may foster positive math
      motivational beliefs and achievement among young women.

PMID- 29570892
TI  - A Temperature-Controlled, Conductive PANI@CNFs/MEO2 MA/PEGMA Hydrogel for
      Flexible Temperature Sensors.
AB  - Electrically conductive, yet stimuli-responsive hydrogels are highly desirable
      for many technological applications. However, the discontinuous conductivity of
      hydrogels during the response process has become a bottleneck that limits their
      application. To overcome this constraint, a linearly tunable, electrically
      conductive hydrogel is prepared using in-situ polymerized polyaniline (PANI) on a
      CNFs/MEO2 MA/PEGMA hydrogel (PANI@CMP hydrogel) substrate. The PANI@CMP hydrogel
      exhibits temperature-tunable electrical conductivity due to the liner
      relationship between thermosensitivity and temperature of the CMP hydrogel
      substrate. Furthermore, the stiffness and elasticity of the resultant hydrogel
      after PANI introduction is enhanced via physical interactions, and the
      compression load is improved by 42%. A highly sensitive temperature sensor is
      therefore fabricated with PANI@CMP hydrogel as the flexible induction element,
      and this sensor achieves temperature monitoring from 20 to 60  degrees C. This
      new temperature-controllable conductive hydrogel has excellent mechanical
      properties, showing great potential for applications in flexible smart sensors,
      conductive fillers, and medical devices.

PMID- 29570891
TI  - Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell
      carcinoma.
AB  - BACKGROUND: Patients with metastatic Merkel cell carcinoma are treated similarly
      to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is
      overexpressed in SCLC and response to PARP inhibitors have been reported in
      patients with SCLC. Our study explores PARP as a therapeutic target in Merkel
      cell carcinoma. METHODS: We evaluated PARP1 expression and Merkel cell
      polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome
      sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4
      Merkel cell carcinoma cell lines. RESULTS: Most Merkel cell carcinomas (74%)
      express PARP1 at high levels. Mutations in DNA-damage repair genes were
      identified in 9 samples (64%), occurred exclusively in head neck primaries, and
      correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in
      MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell
      carcinoma line with highest PARP1 expression. CONCLUSION: Based on PARP1
      overexpression, DNA-damage repair gene mutations, platinum sensitivity, and
      activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP
      inhibitors are warranted in Merkel cell carcinoma.

PMID- 29570893
TI  - Comparison of dispensed medications and forensic-toxicological findings to assess
      pharmacotherapy in the Swedish population 2006 to 2013.
AB  - PURPOSE: To investigate person-level agreement between medication exposure as
      predicted using the PRE2DUP (a prescription-based design to estimate continuous
      drug use) method and postmortem toxicological findings, in the Swedish population
      during the years 2006 to 2013. METHODS: Using the Swedish National Board of
      Forensic Medicine's toxicology database and the Swedish National Board of Health
      and Welfare's registries on causes of death, dispensed medications, and in
      patient care, forensic-toxicological findings were compared with prescription
      based estimates of drug use for 27 medications. We modeled expected drug-use
      periods with the PRE2DUP using an algorithm of demonstrated high validity that
      evaluates personal drug-purchasing patterns with consideration to possible
      stockpiling of drugs and package information. Excluding criteria included self
      inflicted death and recent in-patient care. RESULTS: In data from 18 627
      performed autopsies, as well as 10 160 instances of dispensed drug use, the
      agreement between PRE2DUP drug-use periods and forensic toxicology was, overall,
      moderate (Cohen's kappa: 0.56 [95% confidence interval {CI}: 0.55-0.57]) with a
      positive predictive value, or predicted adherence rate, of 46.0%. The group-level
      predicted adherence and agreement were highest for antidepressants, at 71.0%
      (Cohen's kappa: 0.74 [CI: 0.73-0.76]), and lowest for cardiovascular drugs, at
      21.5% (Cohen's kappa: 0.33 [CI: 0.31-0.36]). Predicted recreational use (negative
      predictive value) was low for all investigated drugs (0.0%-1.4%). The biological
      half-life explained 29% (P = 0.003) of the variability of the false-positive
      rate. CONCLUSIONS: Measured agreement between PRE2DUP-based drug-use estimates
      and forensic-toxicological findings is dependent upon a number of factors,
      including true continuous drug use and postmortem detectability of the
      investigated drugs, as well as the occurrence of unconventional dosing and true
      non-adherence.

PMID- 29570894
TI  - Prophylactic pulmonary vein isolation during isthmus ablation for atrial flutter:
      Three-year outcomes of the PREVENT AF I study.
AB  - INTRODUCTION: The PREVENT AF I study demonstrated that prophylactic pulmonary
      vein isolation (PVI) in patients with pure typical atrial flutter (AFL) resulted
      in substantial reduction of new-onset atrial fibrillation (AF) during 1-year
      follow-up as assessed by continuous implantable cardiac monitor (ICM). The
      objective of this study was to assess 3-year outcomes. METHODS AND RESULTS: Fifty
      patients with documented AFL were randomized to either cavotricuspid isthmus
      (CTI) ablation alone (n = 25) or CTI with concomitant PVI (n = 25). The primary
      endpoint of the study was the occurrence of any atrial tachyarrhythmia with the
      monthly burden exceeding 0.5% on the ICM. At the end of 3 years, freedom from any
      atrial tachyarrhythmia was 48% (95% confidence interval [CI]: 32-72%) in the CTI
      plus PVI group as compared to 20% (95% CI: 9-44%) in the CTI-only group (P =
      0.01). Freedom from redo procedures was also higher: 92% (95% CI: 82-100%) versus
      68% (95% CI: 52-89%), respectively (P = 0.027). The 3-year AF burden favored the
      combined ablation group: 6.2% versus 16.8% (P = 0.03). In the CTI-only group, 12
      (48%) patients were hospitalized compared to 4 (16%) in the PVI + CTI group (P =
      0.03). Two patients in the CTI-only group developed stroke with no serious
      adverse events in the PVI + CTI group. CONCLUSION: Prophylactic PVI in patients
      with only typical AFL resulted in a significant reduction of new-onset AF and
      burden during long-term follow-up as assessed by ICM, with consequent reduction
      in hospitalizations and need to perform repeat ablation for AF.

PMID- 29570896
TI  - Friendless Adolescents: Do Perceptions of Social Threat Account for Their
      Internalizing Difficulties and Continued Friendlessness?
AB  - Adolescents who lack friends at school are at risk of internalizing difficulties.
      This study examined a social-cognitive mechanism underlying friendlessness and
      internalizing difficulties (i.e., depressive symptoms, social anxiety, low self
      esteem). We tested whether perceived social threat (i.e., peer victimization,
      sense of unsafety, and peer misconduct) mediates the association between
      friendlessness and increased internalizing difficulties across middle school.
      Latent variable structural equation modeling was used to test the model among an
      ethnically diverse sample of 5,991 (52% female) adolescents. The results
      demonstrate that friendless sixth-grade students perceived their school
      environment as more threatening by seventh grade, which in turn, increased
      internalizing difficulties from sixth to eighth grade. Perceptions of threat also
      predicted friendlessness at the end of middle school.

PMID- 29570895
TI  - Repeatability, reproducibility, and accuracy of quantitative mri of the breast in
      the community radiology setting.
AB  - BACKGROUND: Quantitative diffusion-weighted MRI (DW-MRI) and dynamic contrast
      enhanced MRI (DCE-MRI) have the potential to impact patient care by providing
      noninvasive biological information in breast cancer. PURPOSE/HYPOTHESIS: To
      quantify the repeatability, reproducibility, and accuracy of apparent diffusion
      coefficient (ADC) and T1 -mapping of the breast in community radiology practices.
      STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Ice-water DW-MRI and T1 gel phantoms
      were used to assess accuracy. Normal subjects (n = 3) and phantoms across three
      sites (one academic, two community) were used to assess reproducibility. Test
      retest analysis at one site in normal subjects (n = 12) was used to assess
      repeatability. FIELD STRENGTH/SEQUENCE: 3T Siemens Skyra MRI quantitative DW-MRI
      and T1 -mapping. ASSESSMENT: Quantitative DW-MRI and T1 -mapping parametric maps
      of phantoms and fibroglandular and adipose tissue of the breast. STATISTICAL
      TESTS: Average values of breast tissue were quantified and Bland-Altman analysis
      was performed to assess the repeatability of the MRI techniques, while the
      Friedman test assessed reproducibility. RESULTS: ADC measurements were
      reproducible across sites, with an average difference of 1.6% in an ice-water
      phantom and 7.0% in breast fibroglandular tissue. T1 measurements in gel phantoms
      had an average difference of 2.8% across three sites, whereas breast
      fibroglandular and adipose tissue had 8.4% and 7.5% average differences,
      respectively. In the repeatability study, we found no bias between first and
      second scanning sessions (P = 0.1). The difference between repeated measurements
      was independent of the mean for each MRI metric (P = 0.156, P = 0.862, P = 0.197
      for ADC, T1 of fibroglandular tissue, and T1 of adipose tissue, respectively).
      DATA CONCLUSION: Community radiology practices can perform repeatable,
      reproducible, and accurate quantitative T1 -mapping and DW-MRI. This has the
      potential to dramatically expand the number of sites that can participate in
      multisite clinical trials and increase clinical translation of quantitative MRI
      techniques for cancer response assessment. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29570897
TI  - Methodological challenges when evaluating potential off-label prescribing of
      drugs using electronic health care databases: A case study of dabigatran
      etexilate in Europe.
AB  - PURPOSE: To report and discuss estimated prevalence of potential off-label use
      and associated methodological challenges using a case study of dabigatran.
      METHODS: Observational, cross-sectional study using 3 databases with different
      types of clinical information available: Cegedim Strategic Data Longitudinal
      Patient Database (CSD-LPD), France (cardiologist panel, n = 1706; general
      practitioner panel, n = 2813; primary care data); National Health Databases,
      Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and
      Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode
      Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus
      hospital data for HES-linkable patients). STUDY PERIOD: August 2011 to August
      2015. Two definitions were used to estimate potential off-label use: a broad
      definition of on-label prescribing using codes for disease indication (eg, atrial
      fibrillation [AF]), and a restrictive definition excluding patients with
      conditions for which dabigatran is not indicated (eg, valvular AF). RESULTS:
      Prevalence estimates under the broad definition ranged from 5.7% (CPRD-HES) to
      34.0% (CSD-LPD) and, under the restrictive definition, from 17.4% (CPRD-HES) to
      44.1% (CSD-LPD). For the majority of potential off-label users, no diagnosis
      potentially related to anticoagulant use was identified. Key methodological
      challenges were the limited availability of detailed clinical information, likely
      leading to overestimation of off-label use, and differences in the information
      available, which may explain the disparate prevalence estimates across data
      sources. CONCLUSIONS: Estimates of potential off-label use should be interpreted
      cautiously due to limitations in available information. In this context, CPRD HES
      linkable estimates are likely to be the most accurate.

PMID- 29570898
TI  - Novel connectivity map normalization procedure for improved quantitative
      investigation of structural thalamic connectivity in temporal lobe epilepsy
      patients.
AB  - BACKGROUND: Connectivity studies targeting the thalamus have revealed patterns of
      atrophy and deafferentiation in temporal lobe epilepsy (TLE). The thalamus can be
      parcellated using probabilistic tractography to demonstrate regions of cortical
      connectivity; however, sensitivity to smaller or less connected regions is low.
      PURPOSE/HYPOTHESIS: To investigate thalamic structural connectivity in a wider
      range of cortical and limbic structures in TLE patients using a novel
      connectivity map normalization procedure. STUDY TYPE: Retrospective.
      POPULATION/SUBJECTS: Patients (N = 23) with medication-resistant TLE and 34
      healthy age-matched controls. FIELD STRENGTH/SEQUENCE: For T1 and diffusion
      weighting a spoiled gradient sequence was used (41 gradient directions [b =
      1000]). For T2 mapping balanced steady-state free precession was used. Images
      were acquired at 3T. ASSESSMENT: Probabilistic tractography and a novel
      normalization procedure allowed comparison of groups with respect to thalamic
      connected volume, quantitative MRI, and diffusion tensor imaging (DTI) metrics.
      STATISTICAL TESTS: Independent samples t-test, Cohen's d, and Mann-Whitney tests.
      RESULTS: Following normalization, significant differences in thalamic connected
      volumes were found in left TLE vs. controls bilaterally within the posterior
      parahippocampal gyrus (L: P = 0.007, confidence interval [CI]: [173.306,1044.41],
      effect size [ES] = 1.072; R: P = 0.017, CI: [98.677,947.653], ES = 0.945), and
      contralaterally in the anterior temporal neocortex (P = 0.01, CI: (-2348.09, 
      333.719), ES = -1.021). This procedure revealed differences in thalamic connected
      volumes, where previously published procedures could not, and provided a basis
      for exploratory analysis of quantitative MRI and DTI metrics. DATA CONCLUSION:
      The novel connectivity map normalization scheme proposed here successfully
      allowed comparison between a wider range of cortical and limbic structures.
      Multiple volumetric and quantitative MRI and DTI-related differences between TLE
      patients and controls were revealed following normalization. With validation from
      a larger cohort, thalamo-temporal connection aberrancies may become useful
      biomarkers of disease states and probabilistic tractography as a procedure for
      identification of thalamic targets in modulatory therapies for TLE. LEVEL OF
      EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1529
      1539.

PMID- 29570899
TI  - Out-of-School Time and Behaviors During Adolescence.
AB  - Although adolescents experience an array of out-of-school time (OST) settings,
      research has primarily focused on these settings in isolation. This study
      examined time in four OST settings (unsupervised time with peers, paid
      employment, sports, and nonsports organized activities) in relation to adolescent
      functioning at age 15 and the end of high school. Individual fixed effects
      analyses provided a more rigorous control of selection into OST activities by
      controlling for time-invariant observable and unobservable characteristics. More
      unsupervised time with peers predicted increases in risky and externalizing
      behaviors, whereas increases in paid employment predicted gains in work
      orientation and self-identity. Time in organized sports was associated with
      increased positive self-identity, highlighting the value of expanding
      consideration of multiple OST contexts and selection effects.

PMID- 29570900
TI  - Temporal trends in safety and complication rates of catheter ablation for atrial
      fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) ablation is increasingly common, but is
      associated with potential major complications. Technology, experience, and
      protocols have evolved significantly in recent times, and may have impacted
      procedural safety. We sought to compare AF ablation safety profiles, including
      complication rates and fluoroscopy times in a "modern" versus "historical"
      cohort. METHODS AND RESULTS: We evaluated consecutive patients undergoing AF
      ablation from a modern cohort (MC) from 2014 to 2015 and a historic cohort (HC)
      from 2009 to 2011 for complications. Major complications were categorized
      according to Heart Rhythm Society guidelines. We included 1,425 patients, 726 in
      the HC and 699 in the MC. The MC was older, had more OSA and less valvular AF.
      Fifty-two (3.5%) procedures suffered major complications across the cohorts, with
      significantly fewer in the MC (5.0% vs. 2.3%, P  =  0.007). The largest
      reductions were seen in vascular, hemorrhagic, ischemic stroke, and
      perforation/tamponade related complications. Periprocedural antiplatelets drugs
      (aHR 2.1 [95 CI 1.1-3.9], P  =  0.02) and force-sensing catheters (aHR 0.4 [95 CI
      0.2-0.9], P  =  0.03) were independently related to major complication rates.
      Direct oral anticoagulants and uninterrupted anticoagulation were not associated
      with complications. There was a decrease in both fluoroscopy (-17.4 minutes [95
      CI 19.2-15.6], P < 0.0001) and radiofrequency ablation times (-561 seconds [95CI 
      750 to -371], P < 0.0001). CONCLUSIONS: The safety profile of AF ablation has
      improved significantly in less than a decade.

PMID- 29570901
TI  - An interesting case of intra-Hisian Wenkebach with left bundle branch block.

PMID- 29570902
TI  - A transcriptomics study of differentiated C2C12 myoblasts identified novel
      functional responses to 17beta-estradiol.
AB  - Previous studies of the role of 17beta-estradiol (E2) in myoblast differentiation
      have produced conflicting data. Therefore, this work aimed to determine the role
      of E2 on myoblast differentiation and specific myofiber formation. Murine C2C12
      myoblasts were cultured in proliferation medium or differentiation medium/10 nM
      E2. The role of E2 on specific myosin heavy chain (MyHC) or estrogen receptor
      (ER) expression was examined using real-time quantitative RT-PCR (RT-qPCR).
      Transcriptome studies of E2 on myoblast differentiation were accomplished by
      microarray analyses. The expression levels of candidate genes from microarrays
      and four and a half LIM domains 1 (Fhl1) were detected with RT-qPCR. E2 in
      differentiation medium significantly up-regulated MyHC I expression, but exerted
      the opposite effects on MyHC II a, MyHC II b, and MyHC II d. Both ER-alpha and ER
      beta were decreased in differentiated C2C12, and E2 partially restored ER-beta
      expression. Sixty-two up-regulated and 116 down-regulated genes treated by E2
      were identified, and RT-qPCR validation results showed seven cytoskeletal genes
      (Myh8, Cenpe, Jak3, Obscn, Ldb3, Mybpc2, Col4a3bp), three genes related to ion
      channels (Kcnq1, Lrrc26, P2rx3) and Fhl1 transcript 2 were associated with the
      effects of E2 on myoblast differentiation. These findings suggested E2 helped
      slow type MyH I fiber formation and impeded fast 2A, 2X/D, and 2B fiber
      formation.

PMID- 29570904
TI  - Toward a New Understanding of Ethnic-Racial Settings for Ethnic-Racial Identity
      Development.
AB  - The purpose of this conceptual article is to advance theory and research on one
      critical aspect of the context of ethnic-racial identity (ERI) development:
      ethnic-racial settings, or the objective and subjective nature of group
      representation within an individual's context. We present a new conceptual
      framework that consists of four dimensions: (1) perspective (that settings can be
      understood in both objective and subjective terms); (2) differentiation (how
      groups are defined in a setting); (3) heterogeneity (the range of groups in a
      setting); and (4) proximity (the distance between the individual and the
      setting). Clarifying this complexity is crucial for advancing a more coherent
      understanding of how ethnic-racial settings are related to ERI development.

PMID- 29570903
TI  - TRPC1/3/6 inhibition attenuates the TGF-beta1-induced epithelial-mesenchymal
      transition in gastric cancer via the Ras/Raf1/ERK signaling pathway.
AB  - Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-beta1
      induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad
      dependent pathways. Nevertheless, few studies have focused on the activation of
      non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously
      expressed in various cell types and are involved in many cellular functions.
      However, their roles in GC are not well elucidated. This study aimed to determine
      whether TRPC participates in the TGF-beta1-induced EMT of GC and to investigate
      the potential mechanisms. Immunofluorescence staining was performed to examine
      the distribution and expression of TRPCs and EMT-related proteins in SGC-7901
      cells incubated with or without TGF-beta1. The expression of TRPC1/3/6 and EMT
      related molecules, including E-cadherin, vimentin, and alpha-SMA, was detected by
      qRT-PCR and Western blotting. Additionally, the underlying mechanism was
      determined by treating cells with pharmacological inhibitors and examining the
      levels of proteins involved in the main signaling cascades using Western
      blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following
      TGF-beta1 stimulation, the expression of vimentin, alpha-SMA, and TRPC1/3/6
      increased and E-cadherin expression decreased, accompanied by activation of the
      Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2
      signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK
      inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6
      inhibition attenuated the TGF-beta1-induced EMT in GC by suppressing Ras/Raf1/ERK
      signal transduction.

PMID- 29570905
TI  - Development and validation of oral health-related quality of life measure in oral
      submucous fibrosis.
AB  - OBJECTIVE: The aim of this study was to develop and assess the validity and
      reliability of disease-specific oral health-related quality of life (OHRQoL)
      instrument for oral submucous fibrosis (OSF). MATERIALS AND METHODS: Items for
      the OHRQoL-OSF were generated from personal interviews and focus group
      discussions, the existing questionnaires, reviews of literature and inputs from
      expert's panel. Item reduction was performed by clinical impact method followed
      by pretesting of the developed questionnaire. The validity and reliability of the
      instrument were then examined. RESULTS: Forty-five items were generated from
      qualitative data and item pooling from various sources. After item reduction, 17
      items were finalized with four domain-structure having Eigenvalues greater than
      1. OHRQoL-OSF was shown to be valid in distinguishing patients with varying
      degrees of OSF severity. For the concurrent validity, the observed impact of OSF
      based on OHRQoL-OSF significantly correlated with Oral Health Impact Profile and
      global self-ratings of oral health and overall well-being. OHRQoL-OSF and all its
      domains demonstrated good internal consistency reliability with Cronbach's alpha
      ?0.7 and excellent test-retest reliability (ICC = 0.96). CONCLUSION: The first
      disease-specific OHRQoL-OSF instrument appeared to be highly reliable and valid
      measure for assessing impact of OSF on life quality.

PMID- 29570906
TI  - Hamartomatous inverted polyp of the sigmoid colon: A case demonstrating its
      immunohistochemical characteristics.

PMID- 29570907
TI  - Randomized pilot study on probiotic effects on recurrent candidiasis in oral
      lichen planus patients.
AB  - : Some patients with oral lichen planus (OLP) experience recurrent oral
      candidiasis(OC). Probiotic bacteria have shown to reduce the oral Candida count
      in vivo. OBJECTIVE: To study whether probiotic intervention reduces recurrent OC
      in patients with OLP. MATERIAL AND METHODS: Twenty-two patients with symptomatic
      OLP were enrolled in the double-blinded, randomized, placebo-controlled
      intervention study. Lozenges containing Lactobacilli reuteri (DSM 17938 and ATCC
      PTA 5289) or placebo were dissolved intra-orally three times daily for 16 weeks,
      after which patients were followed up for 36 weeks. Mucosal symptoms, VAS pain,
      OLP severity score, plaque index (PI) and gingival index (GI), Candida
      count/carriage, and OC and/or need for symptomatic treatment were registered.
      Statistical significance was set at p < .05. RESULTS: No difference was observed
      between the groups during the intervention or follow-up in terms of recurrent OC
      (p = .966) or need for symptomatic treatment (p = 1.000). There was no difference
      in terms of Candida count (p = .96) or carriage over time (p = .511). GI
      decreased in the probiotic group and increased in the placebo group (p = .046).
      OLP severity score decreased in both groups during the study period (p = .039).
      Across the entire study period, the placebo group had higher VAS pain score (p =
      .037). CONCLUSIONS: Probiotic intervention did not reduce recurrent OC or Candida
      count/carriage, but the study experienced recruitment problems, which may have
      influenced results.

PMID- 29570908
TI  - Mesothelial/monocytic incidental cardiac excrescence with bone marrow.

PMID- 29570909
TI  - Effect of prolonged hospitalization for threatened preterm labor on maternal and
      fetal vitamin D levels.
AB  - AIM: We aimed to evaluate the effect of prolonged hospitalization for threatened
      preterm labor (TPL) on maternal and fetal vitamin D status. METHODS: This was a
      retrospective cohort study, spanning 4 years, including 18 women with TPL and 36
      women with normal pregnancy who received prenatal care for a singleton pregnancy
      at our center. TPL cases were women who were admitted to our hospital after the
      second trimester test for at least 28 days, during which time the third trimester
      test was also performed. Controls were randomly sampled from women matched for
      age as well as the season during which the third trimester test was performed.
      Serum 25-hydroxyvitamin D (25(OH)D) concentration in maternal blood was compared
      between the two groups at second trimester, third trimester and in the umbilical
      cord blood at delivery. RESULTS: The mean +/- SD of maternal serum 25(OH)D
      concentration in the TPL group (14.0 +/- 3.0 ng/mL) was significantly lower than
      that in the control group (17.8 +/- 5.9 ng/mL) (P < 0.01) in the third trimester,
      although there was no significant difference in the second trimester (P = 0.30).
      There was a significant reduction (P < 0.01) in the maternal serum 25(OH)D from
      the second to third trimester in the TPL group, compared to the control group (P
      = 0.60). There was no significant difference between the two groups in umbilical
      cord blood 25(OH)D concentrations at delivery (P = 0.41). CONCLUSION: Prolonged
      hospitalization for TPL reduced the maternal vitamin D status but did not
      influence the neonatal status at delivery.

PMID- 29570910
TI  - Adult brain activation during visual learning and memory tasks. An experimental
      approach to translational neuroscience.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Human brain connectome is a new and rapidly
      developing field in neuroscience. The pattern of structural and functional
      connectivity in the brain is not fixed but is continuously changing in response
      to experiences. Exploring these phenomena opens a powerful arsenal of analyses
      and computational approaches that could provide important new insights into
      clinical and cognitive neuroscience. The aim of the present study was to
      investigate the activations of adult brain cortical areas during a memory task
      performance by using functional MRI with a specific focus on gender differences.
      METHODS: Twenty-nine right-handed subjects (15 men and 14 women) were scanned.
      The memory paradigm consisted of 4 consecutive sets of "on" and "off" blocks with
      a total duration of 4 minutes. The subjects were first presented with 4 pictures
      (fixation F-part) of the same theme-landscapes, portraits, anatomical images of
      internal organs, and geometric figures denoted by specific mismatching nouns
      (seasons, personal names, internal organs, and figures), followed by 3 of the
      presented pictures and questions for memory evaluation (recall R-part). For the
      active conditions, the participants were instructed to read the statements
      carefully and answer with a button press. RESULTS: We found reliable occipital
      and temporal signal responses across the block design contrasts with statistical
      significant differences within the groups in both genders. Statistical
      significance in brain cortical activation was not found between men and women.
      CONCLUSION: The results highlighted several detailed distinctions between the
      genders and potential future directions in brain activation studies as part of
      the multidisciplinary approach in translational neuroscience.

PMID- 29570911
TI  - Methodological Challenges to collecting Clinical and Economic Outcome Data:
      Lessons from the Pilot Dialysis Outcomes India Study.
AB  - INTRODUCTION: Contemporary data on clinical and economic outcomes and quality of
      care amongst dialysis patients in India are not available. This pilot prospective
      study evaluated the feasibility of data collection and follow up within routine
      dialysis practice to inform setting up a dialysis registry. METHODS: An
      electronic instrument was developed to collect information on clinical and socio
      demographic characteristics, outcome and out-of-pocket expenditure on incident
      patients commencing haemodialysis (HD) at two centres. Dialysis unit staff were
      trained in collecting and entering information on an electronic case record form.
      Patients were followed up at 1, 3, 6, 9 and 12 months to ascertain outcomes and
      treatment related costs. RESULTS: A total of 119 patients (37 females, age
      47.5+17.2 years) were enrolled. After 1 year, 38 (32%) patients were continuing
      on HD; 35 (29%) had died, 30 (25%) underwent a kidney transplant, and 16 (13%)
      had stopped dialysis. We noted a high prevalence of catastrophic health
      expenditure. Data collection was facilitated by appointing a designated staff
      member who received an incentive. Collection of financial information, clinical
      course for patients transferring out of the primary unit and the cause of death,
      when it occurred out of hospital was challenging. CONCLUSIONS: Prospective data
      collection of incident dialysis patients was feasible but is resource-intensive.
      High out-of-pocket costs force some patients to stop dialysis and can generate a
      sense of despair. Poor patient experiences and suspicion over the use of such
      data adversely affects collection of important clinical and health economic data.

PMID- 29570912
TI  - A case of severe soft tissue infection due to Streptococcus tigurinus diagnosed
      by necropsy in which genomic analysis was useful for clarifying its
      pathogenicity.
AB  - Post-mortem detection of pathogenetic microorganisms in severe infectious death
      is significantly important for diagnosing the cause of death as well as for
      public health. However, it is difficult to recognize whether a microorganism
      detected from post-mortem materials is truly pathogenic or not. We report a case
      of severe soft tissue infection due to Streptococcus oralis subsp. tigurinus (S.
      tigurinus), a recently reported species, in which whole-genome analysis was
      performed to clarify its pathogenicity. A 46-year-old woman had died with
      symptoms of a severe infectious disease. A post-mortem examination was performed
      by a medical examiner. The external findings suggested a soft tissue infection;
      subsequently, pathological specimens sampled by necropsy revealed findings
      compatible with necrotizing fasciitis. In the post-mortem bacterial test, S.
      tigurinus was detected from the localized autopsy sample. Whole-genome sequencing
      was performed to analyze its pathogenicity and detected a strain of S. tigurinus
      with genetic determinants that were specific and unique to its highly virulent
      strains as a result of gene annotation. Utilizing various technologies, such as
      whole-genome sequencing, may be a powerful tool for diagnosing the cause of
      infectious death accurately and safely.

PMID- 29570913
TI  - Children with cochlear implants in infancy: predictors of early vocabulary.
AB  - BACKGROUND: Language outcomes for children with cochlear implants (CIs) vary
      widely, even for those implanted before 2 years of age. Identifying the main
      influencing factors that account for some of the variability is important in
      order to provide information to guide appropriate clinical and intervention
      services for young children with CIs. However, there is limited research focusing
      on the predictors of early vocabulary development for children implanted in
      infancy. AIMS: To identify significant predictors of vocabulary (12-15 months
      post-implant) for a sample of 33 children with CIs, the majority implanted
      between 6 and 10 months of age, drawing on predictors of vocabulary reported for
      children with normal hearing. Of particular interest was the impact of pre
      implant development and use of gestures. METHODS & PROCEDURES: Children with
      severe to profound hearing loss, and no other known disabilities, were recruited
      from CI clinics in Australia before receiving their CIs. Subscales from the
      Bayley Scales-III (receptive and expressive communication, gross and fine motor,
      and cognition) were used to assess their development at that time. Using the
      Macarthur-Bates Communicative Development Inventory (Words and Gestures) we
      documented the children's (1) use of gestures at six data-collection times 3
      months apart; and (2) vocabulary at the last three time points. Time since
      implant and time to consistent use of the CIs were also included as potential
      predictors. Data were analysed using generalized linear models, assuming a
      negative binomial response with a log-link function. Stepwise variables selection
      was followed to retain a smaller number of the covariates. OUTCOMES & RESULTS: A
      year after implantation, the significant predictors identified for vocabulary
      were pre-implant receptive communication and early gesture use. Together with
      fine motor and cognitive skills, these two variables were also significant
      predictors of vocabulary 3 months later. With maternal education entered into the
      models, higher vocabulary scores were significantly associated with higher
      maternal education 12 months post-implantation, but not 15 months. CONCLUSIONS &
      IMPLICATIONS: Pre-implant abilities are important in explaining some variability
      in the early vocabulary of infants with CIs, together with their use of early
      gestures post-implantation. That is, having a non-verbal means to express a
      concept can assist in their development of oral vocabulary. Identifying
      strategies to help develop fine motor skills for infants with CIs, and
      encouraging their use of gestures to communicate their needs/intentions, are
      likely to be of benefit.

PMID- 29570914
TI  - Voriconazole concentration is inversely correlated with corticosteroid usage in
      immunocompromised patients.
AB  - BACKGROUND: Voriconazole (VRCZ) is a broad-spectrum antifungal agent that can be
      administered both orally and intravenously. A high level of intra- and
      interindividual variability in serum drug therapeutic concentrations has been
      reported. We analyzed the influence of corticosteroid use on serum VRCZ
      concentration by assessing the correlation between corticosteroid dose and VRCZ
      trough level. METHODS: Immunocompromised patients treated with VRCZ with or
      without corticosteroid use from June 2010 to March 2017 (6 years and 8 months)
      were reviewed in our institute. VRCZ and the corticosteroids were administered
      orally or intravenously. Corticosteroid treatment was considered as "concurrent"
      only if it was administered within 3 days before or after the initiation of VRCZ.
      All corticosteroids were converted to a prednisolone-based dosage according to
      their anti-inflammatory effect (relative glucocorticoid activity). VRCZ
      concentration was measured at the trough point on the day of steady state.
      RESULTS: A total of 85 samples were obtained from 38 patients. The medical
      records of 23 women and 15 men, with a median age of 61 years (range: 35-86),
      were reviewed. Twenty-one patients (55.3%, 21/38) received chemotherapy, and 28
      (73.7%, 28/38) received corticosteroid therapy. The average and median daily
      doses of corticosteroids were 59.2 and 89.8 mg, respectively (range: 0.714-377).
      VRCZ concentration was inversely correlated with corticosteroid dose (r = -.26).
      The VRCZ concentration was significantly decreased in the corticosteroid user
      compared to nonuser (P = .013). We evaluated the association of VRCZ
      concentration and corticosteroid dose in 3 patients among our cohorts for whom
      more than 5 points of data were available. Intraindividual analysis revealed the
      trough level of VRCZ concentration decreased as the corticosteroid dose
      increased. The patients' underlying diseases were hematological diseases (n = 25)
      and immunological diseases (n = 13). Among accrual patients, no patients were
      undergoing stem cell transplantation, and no patients were treated with known
      confounders such as calcineurin inhibitors or phenytoin. CONCLUSIONS: VRCZ might
      be metabolized by an enzyme induced by corticosteroid treatment; therefore,
      intraindividual variation in VRCZ metabolism should be considered prior to
      concurrent treatment, especially for patients with hematological malignancies
      treated with corticosteroids.

PMID- 29570915
TI  - Ischemia-modified albumin in preterm infants born to mothers with pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia (PE) carries an increased risk for maternal and/or
      fetal mortality or serious morbidity. PE is associated with ischemia and
      increased oxidative stress in the placenta, which may lead to modification of
      plasma albumin to ischemia-modified albumin (IMA). The aim of this study was to
      investigate IMA and hematological parameters in mothers and in premature infants
      in normal and in pre-eclamptic pregnancies. METHODS: Twenty-five pregnant women
      with PE and their premature newborns were categorized as the PE group, and 25
      normotensive pregnant women and their premature newborns as the control group.
      Preterm infants are classified as small for gestational age (SGA) or non-SGA
      according to the Fenton preterm growth chart. Serum IMA, complete blood count
      (CBC), liver function tests (LFT), renal function tests (RFT), albumin, and C
      reactive protein were measured in the mothers immediately before birth, and in
      the cord blood and serum of the newborns at 6 and 24 h after birth. Clinical and
      demographic data were recorded for both groups. RESULTS: While IMA, LFT and RFT
      were significantly increased in the PE group compared with the control group,
      albumin and CBC were significantly lower in the PE group. A total of 40% of PE
      newborns were SGA, 30% of whom had severe SGA (birthweight <3rd percentile). Cord
      IMA was significantly increased in all preterm neonates in the PE group compared
      with the control group. No mothers or neonates died. CONCLUSION: Serum IMA in
      addition to the prevalence of SGA were significantly increased in the PE group.
      Cord blood IMA, therefore, might be a predictive biomarker for SGA in PE
      pregnancies.

PMID- 29570916
TI  - Factors affecting propofol dosage for sedation in pediatric oncology.
AB  - BACKGROUND: There is limited reference data for determining the appropriate dose
      of propofol for individual patients. Therefore, we investigated the factors
      affecting propofol dosage for pediatric patients undergoing sedation for computed
      tomography (CT) simulation. METHODS: We retrospectively analyzed the electronic
      medical records of pediatric patients who underwent CT simulation for proton
      therapy following a cancer diagnosis at the National Cancer Center (Korea)
      between 1 May 2012 and 30 April 2016. We evaluated the following factors, which
      reflect comorbidities or chronic illness in pediatric oncology patients: age,
      tumor lesion, preterm birth, American Society of Anesthesiologists (ASA)
      classification, pre-sedation temperature, history of propofol use, nothing by
      mouth time, chemotherapy history, pre-sedation laboratory findings, regular
      medication (opioids, anticonvulsants), and use of diuretics. A regression
      analysis was performed and P < 0.05 was considered statistically significant.
      RESULTS: Electronic medical records of 84 pediatric cancer patients were used in
      the analysis. Patients in ASA classes 1-2 required approximately 43% more
      propofol than patients in classes 3-4 (exp(beta), 1.43; 95%CI: 1.21-1.69, P <
      0.001). CONCLUSION: American Society of Anesthesiologists class 3 or 4 is an
      independent indicator of decreased propofol dosage for pediatric oncology
      patients during sedation.

PMID- 29570918
TI  - Letter to 'Scoring model to predict massive post-partum bleeding in pregnancies
      with placenta previa: A retrospective cohort study': The best scoring model may
      depend on the situation.

PMID- 29570917
TI  - Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV
      seropositive kidney transplant recipients receiving rabbit anti-thymocyte
      globulin induction therapy: A pilot study.
AB  - BACKGROUND: Some studies have suggested that rATG treatment may be associated
      with an increased incidence of CMV infection and delayed CMV immune response.
      However, the evidences supporting this matter are scarce. This study aims to
      characterize the kinetic of the CMV-specific T-cell immune response before and
      after rATG induction therapy and the relationship with the development of CMV
      infection in CMV-seropositive kidney transplant recipients. METHODS: An
      observational prospective study of CMV-seropositive kidney transplant patients
      that received rATG induction therapy was performed. A pretransplant sample was
      obtained before the surgery to determine the CMV-specific immunity. CMV viral
      load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were
      determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post
      transplantation. RESULTS: A total of 23 patients were included in the study. CMV
      prophylaxis was administrated for a media of 90 days after transplantation. At
      the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median
      value of 0.31% CD8+ CD69+ INF-gamma+ T cells at a median of 16 weeks post
      transplantation. Five patients never acquired CMV-specific immunity. No
      statistically significant association between CMV infection and CMV-specific T
      cell immune response (P = .086) was observed. However, patients with positive
      pretransplant CMV-specific immunity developed earlier immunity and achieved
      higher levels of CD8+ CD69+ INF-gamma+ T-cell post-transplantation than patients
      with negative pretransplant immunity. CONCLUSIONS: CMV-specific immune monitoring
      in addition to CMV-serology may be useful to stratify patient's risk of CMV
      infection before transplantation.

PMID- 29570920
TI  - The nomogram of prenasal thickness and nasal bone ratio and its relationship with
      nuchal fold in second-trimester fetal ultrasound.
AB  - AIM: We aimed to define the normal values of second-trimester fetal prenasal
      thickness and nasal bone length ratio (PNT/NBL) in a low-risk Turkish population
      and investigate the relationship between the increased PNT and nuchal fold (NF).
      METHOD: We retrospectively reviewed the data of 650 cases considered to be
      euploid fetuses who presented to our clinic between December 2013 and September
      2014 for a second-line ultrasound between 17 and 24 weeks. Their PNT, NBL, NF and
      biometric (BPD, HC, AC, FL and HL) measurements were recorded. RESULTS: A total
      of 650 cases considered to be euploid fetuses were included in this study. There
      was a linear increase in PNT with the gestational weeks (mean value 3.01 at weeks
      17-18 and 3.76 at weeks 23-24). The PNT/NB ratio showed a slight decrease in
      advancing gestational weeks (mean value 0.57 at weeks 17-18 and 0.50 at weeks 23
      24). The 95th percentile value of the PNT/NB ratio, independent of the
      gestational week, was 0.76. The values of both PNT and NF increased with
      advancing gestational weeks, but there was no statistically linear increase
      between PNT and NF (R2 : 0.115). CONCLUSION: In this study, we provided a
      nomogram of the PNT/NB ratio. Both NF thickness and PNT should be dealt with as
      two separate markers. Although the formation mechanisms are thought to be the
      same in both of them, a strong linear relationship does not exist between them.

PMID- 29570919
TI  - De novo CMV-associated collapsing focal segmental glomerulosclerosis in a kidney
      transplant recipient.
AB  - Collapsing focal segmental glomerulosclerosis (FSGS) is a variant of FSGS and is
      associated with severe nephrotic syndrome and acute kidney injury and can occur
      after kidney transplantation. The exact mechanism of collapsing FSGS after kidney
      transplantation is unknown, but potential causes include autoimmune diseases,
      certain malignancies, bisphosphonates, m-TOR inhibitors, interferon-alpha, HIV
      infection, and other viruses. We describe a case of de novo Cytomegalovirus (CMV)
      associated collapsing FSGS in a kidney transplant recipient with a UL97
      phosphotransferase mutation that was successfully treated with intravenous
      ganciclovir, intravenous immunoglobulin, and steroids.

PMID- 29570921
TI  - Confirmed microsporidial graft infection in a HIV-negative renal transplant
      recipient: A case report and review of the literature.
AB  - Microsporidia are intracellular organisms most commonly known to cause
      opportunistic infection in patients with human immunodeficiency virus (HIV).
      There have been several case reports of infection in solid organ and bone marrow
      transplant recipients. Here, we report a case of a non-HIV-infected renal
      transplant patient with microsporidiosis of the renal tract associated with acute
      graft dysfunction. We also review the literature of 12 previously reported cases
      of microsporidiosis in patients with renal transplants who had described graft
      involvement. We review the pattern of illness as well as the common renal biopsy
      features when microsporidial infection is associated with renal graft infection.

PMID- 29570922
TI  - Perspectives of patients with haematological cancer on how clinicians meet their
      information needs: "Managing" information versus "giving" it.
AB  - OBJECTIVES: Practitioners treating patients with haematological cancers have
      extensive clinical information available to give to patients, and patients need
      to be informed. However, many patients want to be protected from having
      information that is too detailed or threatening. To illuminate how practitioners
      can address this dilemma and help patients feel appropriately informed, we
      explored patients' experience of feeling informed or uninformed. METHODS: Semi
      structured interviews were conducted with 20 patients who had been diagnosed with
      haematological cancer and had recently received results from clinical
      investigations or from evaluations of treatment response. Inductive and
      interpretive analysis of the transcribed audio-recorded interviews drew on
      constant comparison. RESULTS: Patients described the need for practitioners
      carefully to manage the information that they provided, and many felt alarmed by
      information that they did not experience as having been managed for them. A few
      patients who had difficulty trusting practitioners were not content with the
      information provided. CONCLUSIONS: These findings can be understood using
      attachment theory, whereby practitioners' careful management of information
      demonstrates their care for patients, and patients' trust in the practitioner
      enables them to feel informed. It follows that, when patients do not feel
      informed, the solution will not necessarily be more information but might be to
      help patients feel more secure in a caring clinical relationship.

PMID- 29570923
TI  - Cultural factors influencing Japanese nurses' assertive communication: Part 2 -
      hierarchy and power.
AB  - Hierarchy and power characterize health-care relationships around the world,
      constituting a barrier to assertive communication and a risk to patient safety.
      This issue is more problematic and complex in countries such as Japan, where deep
      seated cultural values related to hierarchy and power persist. The current paper
      is the second of two that present the findings from a study exploring Japanese
      nurses' views and experiences of how cultural values impact assertive
      communication for health-care professionals. We conducted semistructured
      interviews with 23 registered nurses, following which data were analyzed using
      directed content analysis. Two overarching themes emerged from the analysis:
      hierarchy/power and collectivism. In the present study, we focus on cultural
      values related to hierarchy and power, including differences in professional
      status, gender imbalance, seniority/generation gap, bullying, and
      humility/modesty. The findings from our research provide meaningful insights into
      how Japanese cultural values influence and constrain nurses' communication and
      speaking up behaviors, and can be used to inform educational programs designed to
      teach assertiveness skills.

PMID- 29570924
TI  - The impact of global warming on germination and seedling emergence in Alliaria
      petiolata, a woodland species with dormancy loss dependent on low temperature.
AB  - The impact of global warming on seed dormancy loss and germination was
      investigated in Alliaria petiolata (garlic mustard), a common woodland/hedgerow
      plant in Eurasia, considered invasive in North America. Increased temperature may
      have serious implications, since seeds of this species germinate and emerge at
      low temperatures early in spring to establish and grow before canopy development
      of competing species. Dormancy was evaluated in seeds buried in field soils.
      Seedling emergence was also investigated in the field, and in a thermogradient
      tunnel under global warming scenarios representing predicted UK air temperatures
      through to 2080. Dormancy was simple, and its relief required the accumulation of
      low temperature chilling time. Under a global warming scenario, dormancy relief
      and seedling emergence declined and seed mortality increased as soil temperature
      increased along a thermal gradient. Seedling emergence advanced with soil
      temperature, peaking 8 days earlier under 2080 conditions. The results indicate
      that as mean temperature increases due to global warming, the chilling
      requirement for dormancy relief may not be fully satisfied, but seedling
      emergence will continue from low dormancy seeds in the population. Adaptation
      resulting from selection of this low dormancy proportion is likely to reduce the
      overall population chilling requirement. Seedling emergence is also likely to
      keep pace with the advancement of biological spring, enabling A. petiolata to
      maintain its strategy of establishment before the woodland canopy closes.
      However, this potential for adaptation may be countered by increased seed
      mortality in the seed bank as soils warm.

PMID- 29570925
TI  - An epigenetic breeding system in soybean for increased yield and stability.
AB  - Epigenetic variation has been associated with a wide range of adaptive phenotypes
      in plants, but there exist few direct means for exploiting this variation. RNAi
      suppression of the plant-specific gene, MutS HOMOLOG1 (MSH1), in multiple plant
      species produces a range of developmental changes accompanied by modulation of
      defence, phytohormone and abiotic stress response pathways along with methylome
      repatterning. This msh1-conditioned developmental reprogramming is retained
      independent of transgene segregation, giving rise to transgene-null 'memory'
      effects. An isogenic memory line crossed to wild type produces progeny families
      displaying increased variation in adaptive traits that respond to selection. This
      study investigates amenability of the MSH1 system for inducing agronomically
      valuable epigenetic variation in soybean. We developed MSH1 epi-populations by
      crossing with msh1-acquired soybean memory lines. Derived soybean epi-lines
      showed increase in variance for multiple yield-related traits including pods per
      plant, seed weight and maturity time in both glasshouse and field trials.
      Selected epi-F2:4 and epi-F2:5 lines showed an increase in seed yield over wild
      type. By epi-F2:6, we observed a return of MSH1-derived enhanced growth back to
      wild-type levels. Epi-populations also showed evidence of reduced epitype-by
      environment (e * E) interaction, indicating higher yield stability. Transcript
      profiling of epi-lines identified putative signatures of enhanced growth
      behaviour across generations. Genes related to cell cycle, abscisic acid
      biosynthesis and auxin response, particularly SMALL AUXIN UP RNAs (SAURs), were
      differentially expressed in epi-F2:4 lines that showed increased yield when
      compared to epi-F2:6 . These data support the potential of MSH1-derived
      epigenetic variation in plant breeding for enhanced yield and yield stability.

PMID- 29570926
TI  - Formation of Aminocyclopentadienes from Silyldihydropyridines: Ring Contractions
      Driven by Anion Stabilization.
AB  - Highly functionalized aminocyclopentadienes can be formed through the
      rearrangement of anions generated from readily prepared 6-silyl-1,2
      dihydropyridines by desilylation with fluoride. The scope and generality of the
      reaction was defined, and diverse transformations were performed on the highly
      functionalized products. A mechanism and driving force for the rearrangement were
      identified from experiments and DFT calculations.

PMID- 29570927
TI  - Transgenerational plasticity in Silene vulgaris in response to three types of
      stress.
AB  - The environment experienced by plants can influence the phenotype of their
      offspring. Such transgenerational plasticity can be adaptive when it results in
      higher fitness of the offspring under conditions correlated with those
      experienced by the mother plant. However, it has rarely been tested if such
      anticipatory parental effects may be induced with different environments. We grew
      clonal replicates of Silene vulgaris under control conditions and three types of
      stress (nutrient deficiency, copper addition and drought), which are known from
      natural populations of the species. We then subjected offspring from differently
      treated mother plants to each of the different stress treatments to analyse the
      influence of maternal and offspring environment on performance and several
      functional traits. Current stress treatments strongly influenced biomass and
      functional traits of the plants, mostly in line with responses predicted by the
      theory of functional equilibrium. Plant performance was also influenced by
      maternal stress treatments, and some effects independent of initial size
      differences remained until harvest. In particular, stressed mothers produced
      offspring of higher fitness than control plants. However, there was no evidence
      for treatment-specific adaptive transgenerational plasticity, as offspring from a
      mother plant that had grown in a specific environment did not grow better in that
      environment than other plants. Our results indicate that the maternal environment
      may affect offspring traits and performance, but also that this transgenerational
      plasticity is not necessarily adaptive.

PMID- 29570928
TI  - An Organogold(III) Difluoride with a trans Arrangement.
AB  - The trans isomer of the organogold(III) difluoride complex [PPh4 ][(CF3 )2 AuF2 ]
      has been obtained in a stereoselective way and in excellent yield by reaction of
      [PPh4 ][CF3 AuCF3 ] with XeF2 under mild conditions. The compound is both
      thermally stable and reactive. Thus, the fluoride ligands are stereospecifically
      replaced by any heavier halide or by cyanide, the cyanide affording [PPh4 ][trans
      (CF3 )2 Au(CN)2 ]. The organogold fluoride complexes [CF3 AuFx ]- (x=1, 2, 3)
      have been experimentally detected to arise upon collision-induced dissociation of
      the [trans-(CF3 )2 AuF2 ]- anion in the gas phase. Their structures have been
      calculated by DFT methods. In the isomeric forms identified for the open-shell
      species [CF3 AuF2 ]- , the spin density residing on the metal center is found to
      strongly depend on the precise stereochemistry. Based on crystallographic
      evidence, it is concluded that Auiii and Agiii have similar covalent radii, at
      least in their most common square-planar geometry.

PMID- 29570929
TI  - Multicentre international experience of 532-nm laser photoselective vaporization
      with GreenLight XPS in men with very large prostates.
AB  - OBJECTIVES: To describe peri-operative results, functional outcomes and
      complications of laser photoselective vaporization, using the GreenLight system,
      of prostate glands >=200 mL in volume. METHODS: Retrospective analysis of a
      prospectively maintained multicentre database was performed to select a subgroup
      of patients with very large prostates (volume >=200 mL) treated with the
      GreenLight XPS laser. A subgroup of patients with prostate volumes 100-200 mL was
      used for comparison. International Prostate Symptom Score, maximum urinary flow
      rate, postvoid residual urine volume and prostate-specific antigen levels were
      measured at 6, 12, 24, 36 and 48 months. Durability was evaluated using benign
      prostatic hyperplasia re-treatment rate at 12, 24 and 36 months. Additionally,
      complications were recorded using Clavien-Dindo classification. RESULTS: A total
      of 33 patients (38%) had prostates >=200 mL. Baseline characteristics were
      similar between patients with prostates >=200 mL and those with prostates 100-200
      mL. Patients with very large prostates (>=200 mL) had longer operating times (129
      vs 93 min), less energy delivered, a greater number of fibres used (3 vs 2) and a
      higher conversion rate to transurethral resection of the prostate (16% vs 4%). In
      terms of complications and functional outcomes, we did not find any differences
      between the groups. Retreatment rate was also comparable. CONCLUSIONS: Our
      results show that PVP GreenLight XPS-180W is an acceptable technique for very
      large prostates (>=200 mL); however, operating times, energy delivery, fibres
      used and conversion to TURP are a concern in this particular subgroup. This
      should be used for patient counselling and surgery planning.

PMID- 29570931
TI  - Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte
      biology.
AB  - Uveal melanoma (UM) is the most common primary intraocular cancer and has a high
      incidence of metastasis, which lacks any effective treatment. Here, we present
      zebrafish models of UM, which are driven by melanocyte-specific expression of
      activating GNAQ or GNA11 alleles, GNAQ/11Q209L , the predominant initiating
      mutations for human UM. When combined with mutant tp53, GNAQ/11Q209L transgenics
      develop various melanocytic tumors, including UM, with near complete penetrance.
      These tumors display nuclear YAP localization and thus phenocopy human UM. We
      show that GNAQ/11Q209L expression induces profound melanocyte defects independent
      of tp53 mutation, which are apparent within 3 days of development. First,
      increases in melanocyte number, melanin content, and subcellular melanin
      distribution result in hyperpigmentation. Additionally, altered melanocyte
      migration, survival properties, and evasion of normal boundary cues lead to
      aberrant melanocyte localization and stripe patterning. Collectively, these data
      show that GNAQ/11Q209L is sufficient to induce numerous protumorigenic changes
      within melanocytes.

PMID- 29570932
TI  - PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis.
AB  - Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA
      stability and plays important roles in cancer. The mechanisms by which TTP is
      regulated in breast cancer are poorly understood. Using multiple biochemical
      approaches, we found that proviral insertion in murine lymphomas 2 (PIM2) is a
      novel binding partner of TTP. Interestingly, PIM2 decreased TTP protein levels
      independent of its kinase activity. PIM2 instead targeted TTP protein for
      degradation via the ubiquitin-proteasome pathway. Furthermore,
      immunohistochemical staining showed that PIM2 and TTP protein levels were
      negatively correlated in human breast cancer samples. Indeed, PIM2 overexpression
      de-repressed TTP-mediated inhibition of breast cancer cell proliferation and
      migration in vitro and promoted breast tumor xenograft growth in vivo. These
      findings demonstrate an important role for the PIM2-TTP complex in breast cancer
      tumorigenesis, suggesting that PIM2 may represent a potential therapeutic target
      for breast cancer treatment.

PMID- 29570930
TI  - Cigarette smoke enhances oncogene addiction to c-MET and desensitizes EGFR
      expressing non-small cell lung cancer to EGFR TKIs.
AB  - Cigarette smoking is one of the leading risks for lung cancer and is associated
      with the insensitivity of non-small cell lung cancer (NSCLC) to epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, it remains
      undetermined whether and how cigarette smoke affects the therapeutic efficacy of
      EGFR TKIs. In this study, our data showed that chronic exposure to cigarette
      smoke extract (CSE) or tobacco smoke-derived carcinogen benzo[alpha]pyrene,
      B[alpha]P, but not nicotine-derived nitrosamine ketone (NNK), reduced the
      sensitivity of wild-type EGFR-expressing NSCLC cells to EGFR TKIs. Treatment with
      TKIs almost abolished EGFR tyrosine kinase activity but did not show an
      inhibitory effect on downstream Akt and ERK pathways in B[alpha]P-treated NSCLC
      cells. CSE and B[alpha]P transcriptionally upregulate c-MET and activate its
      downstream Akt pathway, which is not inhibited by EGFR TKIs. Silencing of c-MET
      reduces B[alpha]P-induced Akt activation. The CSE-treated NSCLC cells are
      sensitive to the c-MET inhibitor crizotinib. These findings suggest that
      cigarette smoke augments oncogene addiction to c-MET in NSCLC cells and that MET
      inhibitors may show clinical benefits for lung cancer patients with a smoking
      history.

PMID- 29570933
TI  - Jack Halpern (1925-2018).

PMID- 29570935
TI  - Diastereo- and Enantioselective Palladium-Catalyzed Dearomative [3+2]
      Cycloaddition of 3-Nitroindoles.
AB  - Diastereo- and enantioselective cycloaddition of 3-nitroindoles with vinyl
      aziridine was realized under Pd-catalysis using commercially available Walphos as
      the ligand, affording pyrroloindolines in high yields with high diastereo- and
      enantioselectivities. The reaction can be scaled up to a gram scale and the
      reaction products are easily converted to amino pyrroloindoline and other
      pyrroloindoline derivatives.

PMID- 29570934
TI  - Non-erythropoietic erythropoietin-derived peptide protects mice from systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease, which results in
      various organ pathologies. However, current treatment towards SLE is suboptimal.
      Erythropoietin (EPO) has been shown to promote SLE recovery, but clinical
      application can be limited by its haematopoiesis-stimulating effects. EPO-derived
      helix-B peptide (ARA290) is non-erythrogenic but has been reported to retain the
      anti-inflammatory and tissue-protective functions of EPO. Therefore, here we
      investigated the effects and potential mechanisms of ARA290 on SLE. The
      administration of ARA290 to pristane-induced SLE and MRL/lpr mice significantly
      suppressed the level of serum antinuclear autoantibodies (ANAs) and anti-dsDNA
      autoantibodies, reduced the deposition of IgG and C3, and ameliorated the
      nephritis symptoms. Moreover, the serum concentrations of inflammatory cytokine
      IL-6, MCP-1 and TNF-alpha in SLE mice were reduced by ARA290. Further, ARA290
      decreased the number of apoptotic cells in kidney. In vitro experiment revealed
      that ARA290 inhibited the inflammatory activation of macrophages and promoted the
      phagocytotic function of macrophages to apoptotic cells. Finally, ARA290 did not
      induce haematopoiesis during treatment. In conclusion, ARA290 ameliorated SLE,
      which at least could be partly due to its anti-inflammatory and apoptotic cell
      clearance promoting effects, without stimulating haematopoiesis, suggesting that
      ARA290 could be a hopeful candidate for SLE treatment.

PMID- 29570936
TI  - Snake-like surgical forceps for robot-assisted minimally invasive surgery.
AB  - BACKGROUND: Surgical instruments greatly impact the performance of robot-assisted
      minimally invasive surgery (RMIS) because they operate on tissues. METHODS: A
      snake-like surgical instrument, designed with 4 degrees of freedom (DOFs), is
      proposed for RMIS. The DOFs are as follows: opening and closing motions of the
      forceps, rotation of the forceps and bi-directional bending of the instrument.
      The performance of the instrument was evaluated using a prototype in vitro.
      RESULTS: All DOFs of the instrument were experimentally evaluated and proven
      sufficient for RMIS. In vitro testing showed that the operations of the proposed
      model were powerful and steady. CONCLUSIONS: The position and posture of the
      surgical instrument could be adjusted in the body of the patient by its bending
      and rotational movements. The proposed model could therefore work as a competent
      assistant in multi-port RMIS and allow surgeons to perform better.

PMID- 29570937
TI  - Application of pathways activity profiling to urine metabolomics for screening Qi
      tonifying biomarkers and metabolic pathways of honey-processed Astragalus.
AB  - Honey-processed Astragalus, a widely used Qi-tonifying and immunomodulating herb
      in traditional Chinese medicine, has strengthened the tonic effects and achieved
      fewer side effects compared with astragali radix in clinical application. Here,
      we focus on Qi-tonifying biomarkers and pathways of honey-processed Astragalus
      using urine metabolomics that provide the basis for building the linkage between
      metabolites in rat urine and its symptoms. The spleen Qi deficiency model group,
      normal group, astragali radix group, and honey-processed Astragalus group were
      implemented to evaluate Qi-tonifying effects. Twelve potential biomarkers were
      screened by multivariate statistical analysis by using ultra high performance
      liquid chromatography with quadrupole time-of-flight mass spectrometry.
      Furthermore, pathways activity profiling showed unique pathways that are
      primarily involved in tryptophan metabolism, tricarboxylic acids cycle, and
      methionine metabolism. The results demonstrated that metabolomics coupled with
      pathway activity profiling were promising tools. It might serve as a novel
      methodological clue to systematically dissect the underlying Qi-tonifying
      mechanism of honey-processed Astragalus.

PMID- 29570938
TI  - Building Capacity for Evidence-Based Practice: Understanding How Licensed
      Practical Nurses (LPNs) Source Knowledge.
AB  - BACKGROUND: In Canada, all nurses are required to engage in evidence-based
      practice (EBP) as an entry-to-practice competency; however, there is little
      research that examines Licensed Practical Nurses' (LPNs') information seeking
      behaviors or preferred sources of knowledge to conduct EBP. AIMS: Due to the
      differences in education and roles of LPNs and Registered Nurses (RNs), it is
      both necessary and important to gain an understanding of how LPNs utilize
      evidence in their unique nursing practice. The purpose of this study was to
      investigate how LPNs source knowledge for their nursing practice. METHODS: A
      descriptive, cross-sectional survey of LPNs from Alberta, Canada asked
      participants to rank sources of knowledge that inform their practice. Responses
      were correlated with age and years of practice. Analysis of variance was used to
      determine if there were significant mean differences between average scores and
      place of employment. RESULTS: LPN participants used similar sources of knowledge
      as RNs. The top source of knowledge for both RNs and LPNs was the information
      they learn about each individual client and the least utilized sources of
      knowledge were articles published in nursing, medical, and research journals,
      tradition, and popular media. This finding is consistent with previous studies on
      RNs that found nurses do not often access current research evidence to inform
      their practice. LINKING EVIDENCE TO ACTION: Since relatively few LPNs access
      nursing and research journals, it is important to tailor EBP education
      information to the workplace context. Future avenues of research might explore
      the potential of using in-services and webinars to disseminate information and
      skills training on EBP to the LPNs, as this was a popular source of practice
      knowledge.

PMID- 29570939
TI  - Telbivudine associated mitochondrial myopathy.

PMID- 29570940
TI  - Lung ultrasound in diagnosis and follow up of community acquired pneumonia in
      infants younger than 1-year old.
AB  - BACKGROUND: Pneumonia is still a leading cause of illness and death in infants
      worldwide. Lung ultrasound (LUS) is emerging as an extremely valuable non
      ionizing radiation diagnostic tool in diagnosis and follow up of multiple
      paediatric pulmonary diseases. OBJECTIVE: To assess the applicability of LUS in
      diagnosis and follow up of community acquired pneumonia (CAP) in Egyptian infants
      younger than 1-year old. METHODS: LUS and chest X-ray (CXR) were performed in 50
      infants presented with clinical symptoms and signs suggestive of CAP within the
      first 6 hours of admission in our inpatient department, then follow up LUS was
      performed 5 days after admission. RESULTS: This study showed that LUS was
      superior to CXR in initial diagnosis of CAP in infants. LUS detected pneumonia in
      49 (98%) compared to 36 (72%) infants diagnosed by CXR (P < .05). On follow up, 5
      days later, consolidation patch disappeared in 13 (26.5%) infants, diminished in
      size in 27 (55.1%) infants, remained at the same size in 2 (4.1%) infants and
      increased in size in 7 (14.3%) infants. CONCLUSION: This study showed that LUS is
      superior to CXR in diagnosing infants with CAP who are younger than 1-year old.
      It also serves as a safe follow up tool and could support the decision of
      hospital discharge in this category of patients. Further studies with larger
      sample size and longer follow up duration are recommended to confirm the results
      of the present study.

PMID- 29570941
TI  - Real-life practices of chronic thromboembolic pulmonary hypertension screening:
      Results from the REMOTEV observational study.

PMID- 29570942
TI  - Label-free ultra-sensitive visualization of structure below the diffraction
      resolution limit.
AB  - For both fundamental study of biological processes and early diagnosis of
      diseases, information about nanoscale changes in tissue and cell structure is
      crucial. Nowadays, almost all currently known nanoscopy methods rely upon the
      contrast created by fluorescent stains attached to the object or molecule of
      interest. This causes limitations due to the impact of the label on the object
      and its environment, as well as its applicability in vivo, particularly in
      humans. In this paper, a new label-free approach to visualize small structure
      with nano-sensitivity to structural alterations is introduced. Numerically
      synthesized profiles of the axial spatial frequencies are used to probe the
      structure within areas whose size can be beyond the diffraction resolution limit.
      Thereafter, nanoscale structural alterations within such areas can be visualized
      and objects, including biological ones, can be investigated with sub-wavelength
      resolution, in vivo, in their natural environment. Some preliminary results,
      including numerical simulations and experiments, which demonstrate the nano
      sensitivity and super-resolution ability of our approach, are presented.

PMID- 29570943
TI  - The Relationship Between Heart Rate Variability, Psychological Flexibility, and
      Pain in Neurofibromatosis Type 1.
AB  - Individuals with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs)
      can experience chronic pain. Previous research has examined the relationship
      between heart rate variability (HRV) and persistent pain. HRV is an index of
      autonomic nervous system functioning, and reflects the variability in time
      elapsed between heartbeats. Patients with chronic pain tend to exhibit lower HRV,
      which has been associated with poor adaptability, or psychological flexibility,
      to stress. The aim of the current study was to examine relationships between HRV,
      psychological flexibility, and pain in a sample of adolescents and young adults
      (AYAs) with NF1 and PNs. AYA participants (n = 40) 16 to 34 years of age with NF1
      completed baseline measures of pain and psychological functioning, and underwent
      a 5-minute electrocardiogram (ECG). A subset of 20 participants completed follow
      up questionnaires and a second ECG 8 weeks later. Spectral analyses of ECGs
      yielded a measure of high-frequency heart rate variability (HF-HRV). Baseline
      correlations revealed that lower HF-HRV is related to greater inflexibility and
      more pain interference, but not pain intensity. Moreover, psychological
      inflexibility significantly mediated the relationship between HF-HRV and pain
      interference. Finally, regression models indicated that baseline psychological
      inflexibility is a significant predictor of HF-HRV at follow-up and, separately,
      that baseline HF-HRV significantly predicted pain intensity at follow-up. These
      findings suggest complex mind-body processes in the experience of pain in NF1,
      which have not been studied previously. Implications for pain-related
      interventions and future research are discussed.

PMID- 29570944
TI  - Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo
      Biological Evaluations.
AB  - Five new AuIII -peptidodithiocarbamato complexes of the type [AuIII Br2 (dtc-AA1 
      AA2 -OR] (in which AA1 =N-methylglycine (Sar), l/d-Pro; AA2 =l/d-Ala, alpha
      aminoisobutyric acid (Aib); R=OtBu, triethylene glycol methyl ether), differing
      with regard to the amino acid sequence and/or the chiral amino acid
      configuration, were designed to enhance tumor selectivity and bioavailability.
      The gold(III)-based moiety was functionalized to exploit the targeting properties
      of the peptidomimetic ligand toward two peptide transporters (namely PEPT1 and
      PEPT2), which are upregulated in several tumor cells. The compounds were
      synthesized and fully characterized, mainly by means of elemental analysis, one-
      and two-dimensional NMR spectroscopy, FT-IR, and UV/Vis spectrophotometry. The
      crystal structures of three compounds were also solved by X-ray diffraction. In
      vitro cytotoxicity studies using a panel of human tumor cell lines (A549 [non
      small-cell lung carcinoma], MCF-7 [breast cancer], A2780 [ovarian carcinoma],
      H1975 [non-small-cell lung carcinoma], H460 [large-cell lung carcinoma], and A431
      [human epidermoid carcinoma]) showed the dtc-Pro-Aib-OtBu derivative to be very
      effective, with GI50 values much lower than those of cisplatin. This complex was
      thus selected for evaluating stability under physiological conditions and
      possible interactions with serum albumin, as well in PARP-1 enzyme inhibition
      assays and preliminary ex vivo toxicity experiments on healthy rat tissues.

PMID- 29570945
TI  - Diagnostic and prognostic value of serum Cripto-1 in patients with non-small cell
      lung cancer.
AB  - INTRODUCTION: Cripto-1 (CR-1) is a member of the epidermal growth factor (EGF)
      CFC protein family, which is involved in tumor pathogenesis. OBJECTIVES: This
      study aimed to explore the diagnostic and prognostic value of serum CR-1 level in
      patients with non-small cell lung cancer (NSCLC). METHODS: Serum specimens from
      312 NSCLC patients and 120 healthy controls were collected. Serum CR-1 level was
      measured using enzyme-linked immunosorbent assay. RESULTS: The serum CR-1 level
      was significantly elevated in NSCLC patients compared with healthy controls (P <
      .001). Higher serum CR-1 level was associated with advanced TNM stage, lymph node
      metastasis and distant metastasis. With a cutoff value of 1.67 ng/mL, CR-1 showed
      a good diagnostic performance for NSCLC. Kaplan-Meier log rank analysis revealed
      that the low serum CR-1 patients had a better overall survival (OS) and
      progression-free survival (PFS) compared with high CR-1 patients (P = .004 and
      .001, respectively). Further univariate and multivariate Cox regression analyses
      showed that serum CR-1 level was an independent risk factor of prognosis of NSCLC
      patients. CONCLUSIONS: Our study suggests that serum CR-1 level is a useful
      diagnostic and prognostic marker for NSCLC patients.

PMID- 29570946
TI  - Serum 25-hydroxyvitamin D levels in hospitalized adults with community-acquired
      pneumonia.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is the infectious disease with
      the highest number of deaths worldwide. Several studies have shown an association
      between vitamin D deficiency and increases susceptibility to respiratory tract
      infections. OBJECTIVE: The aim of this study was to evaluate the serum 25
      hydroxyvitamin D (25OHD) levels in hospitalized adults in general room with CAP.
      MATERIALS AND METHODS: An observational study was carried out in 207 hospitalized
      adults of both sex with CAP (>18 years) from Rosario city, Argentina (32 degrees 
      52' 18"S) between July 2015 and June 2016. RESULTS: In total, 167 patients were
      included in the data analysis [59% women (57.4 +/- 19.6 years), body mass index
      27.2 +/- 7.8 kg/m2 ]. In brief, 63% showed unilobar infiltrate and 37% were
      multilobar. The CURB-65 index was 66.5% low risk, 16.0% intermediate risk and
      17.5% high risk. According to Charlson comorbidity index (CCI) 53.5% had not
      comorbidity (CCI = 0) and 46.5% showed CCI >= 1. The 25OHD level was: 11.92 +/-
      7.6 ng/mL (51.5%: <10 ng/mL, 33.5%: 10-20 ng/mL, 13.2%: 20-30 ng/mL and 1.8%: >30
      ng/mL). Higher 25OHD were found in male (female: 10.8 +/- 6.7 ng/mL, male: 13.5
      +/- 8.5 ng/mL, P = .02) and 25OHD correlated with age (r = -.17; P = .02). 25
      Hydroxyvitamin D was also correlated with CURB65 index (r = -.13; P = .049), CCI
      (r = -.20, P = .007) and with the 10 years of life expectative (%) (r = .19; P =
      .008). In addition, higher 25OHD were found with lower CCI (CCI 0 = 13.0 +/- 8.2
      ng/mL, CCI >= 1= 10.5 +/- 6.7 ng/mL; P = .0093). CONCLUSIONS: Hospitalized adults
      with CAP have lower 25OHD levels and would be associated with the severity of
      CAP.

PMID- 29570947
TI  - Halogenated Bis(methoxybenzylidene)-4-piperidone Curcuminoids with Improved
      Anticancer Activity.
AB  - A series of readily available curcuminoids with a halogenated bis(4-methoxy/4,5
      dimethoxybenzylidene)-4-piperidone structure were prepared and analyzed for their
      cytotoxic impact on eight human cancer cell lines of five different entities. The
      known 3,4,5-trimethoxybenzylidene curcuminoid 2 a and the new bis-(3-bromophenyl)
      and bis-(3,5-dibromophenyl) derivatives 3 c and 3 d proved to be more strongly
      antiproliferative than the known curcuminoid EF24 against six of these cell
      lines. Compounds 2 a and 3 c caused a distinct increase of reactive oxygen
      species, which eventually elicited apoptosis in 518A2 melanoma cells. Compound 2
      a arrested 518A2 melanoma cells in G1 phase of the cell cycle and had no effect
      on the expression of pro-metastatic matrix metalloproteinases MMP-2 and MMP-9,
      whereas 3 c led to an accumulation of 518A2 cells in the G2 /M phase and to a
      downregulation of MMP-2 expression. In addition, treatment with 2 a and 3 c
      resulted in significant inhibition of colony formation in HCT116 cells. Both 2 a
      and 3 c showed antiangiogenic activity, for example, by inhibiting the formation
      of sub-intestinal veins (SIV) in zebrafish embryos. Compound 3 c was also well
      tolerated by mice and inhibited the growth of HCT116 colon cancer xenografts.

PMID- 29570948
TI  - Nucleoside-Based Self-Assembling Drugs for Localized Drug Delivery.
AB  - We have synthesized a range of gelators based on the nucleoside analogues
      gemcitabine and lamivudine, characterizing representative gels from the series
      using rheology and transmission electron microscopy. Growth inhibition studies of
      gemcitabine derivatives confirmed the feasibility of these compounds as novel
      treatments, indicating the potential of nucleoside-based gelators for localized
      drug delivery.

PMID- 29570949
TI  - Isomerism, Diradical Signature, and Raman Spectroscopy: Underlying Connections in
      Diamino Oligophenyl Dications.
AB  - A diradical dication of a 4,4'-di(bis(1,4-methylphenyl)amino)-p-terphenyl
      oligomer has been characterized in solid-state by Raman spectroscopy and thermo
      spectroscopy together with quantum chemical calculations. The diradical character
      has been evaluated on the basis of the Raman spectra and as a function of
      temperature. A complete understanding of the nature of the changes in solid state
      has been provided based on a pseudo-Jahn-Teller effect, which is feasible owing
      to the fine balance between quinoidal/aromatic extension among consecutive rings
      and steric crowding. This study contributes to the further comprehension of the
      molecular and electronic structures of these particular diradical molecules with
      strong implications on the understanding of the nature of chemical bonds in the
      limits of high electronic correlation or pi-conjugation.

PMID- 29570950
TI  - Comparison of outcomes of laparoscopy-assisted and open proximal gastrectomy with
      jejunal interposition for early gastric cancer in the upper third of the stomach:
      A retrospective observational study.
AB  - INTRODUCTION: Laparoscopy-assisted proximal gastrectomy with jejunal
      interposition (LAPG-JI) is not yet widely used because the three anastomotic
      procedures involved in this operation are technically complicated. This study
      aimed to describe our surgical procedure for LAPG-JI and assess its feasibility
      and safety. METHODS: This was a retrospective study of 70 patients who had
      undergone proximal gastrectomy with jejunal interposition for gastric cancer in
      the upper third of the stomach between July 2007 and October 2016. Of these
      patients, 32 underwent LAPG-JI, and 38 underwent open proximal gastrectomy with
      jejunal interposition. Clinical characteristics and both surgical and
      postoperative outcomes were compared between LAPG-JI and open proximal
      gastrectomy with jejunal interposition. RESULTS: The operation time was longer in
      the LAPG-JI group (189 vs 154 min, P < 0.001) and estimated blood loss was lower
      (30 vs 180 mL, P < 0.001). There were no differences in the rates of early (9.4%
      vs 13.2%) or late postoperative complications (12.5% vs 10.5%). No anastomotic
      leakage was observed in either group. In the LAPG-JI group, the time to first
      eating was shorter, and the white blood cell counts on postoperative days 1 and 7
      and body temperature on postoperative day 3 were lower. The number of additional
      doses of postoperative analgesia was lower in the LAPG-JI group. Reflux
      esophagitis graded C according to the Los Angeles classification was observed in
      only one patient (3.1%) in the LAPG-JI group. CONCLUSION: Although the operation
      time was longer in the LAPG-JI group, the procedure seemed to be feasible and
      safe. Also, it offered the advantages of laparoscopic surgery, including less
      invasiveness and quicker recovery.

PMID- 29570951
TI  - Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the
      developing dorsal and ventral forebrain.
AB  - Little is known about the molecular players driving proliferation of neural
      progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate
      that proliferation of NPCs in the developing forebrain depends on a particular
      combination of cell cycle regulators. We have analyzed the requirements for
      members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In
      the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of
      the cell cycle, we found no significant effects on the proliferation rate of
      cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a
      drastic decrease in the proliferation rate of NPCs, specifically the basal
      progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5
      (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant
      mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an
      increase in cell cycle length and cell cycle exit of mutant basal progenitor
      cells in comparison to controls. In contrast, concomitant ablation of cdk2 and
      cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate
      that the expansion of the basal progenitor pool in the developing telencephalon
      is dependent on the presence of distinct combinations of cdk molecules. Our
      results provide further evidence for differences in the regulation of
      proliferation between apical and basal progenitors during cortical development.
      (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 660-670, 2018.

PMID- 29570952
TI  - Response to: "The use of ultrasound for the estimation of muscle mass: one site
      fits most?"

PMID- 29570953
TI  - A Low-Energy-Gap Thienochrysenocarbazole Dye for Highly Efficient Mesoscopic
      Titania Solar Cells: Understanding the Excited State and Charge Carrier Dynamics.
AB  - Maintaining both a high external quantum efficiency and a large open-circuit
      photovoltage of dye-sensitized solar cells (DSSCs) is a crucial challenge in the
      process of developing narrow-energy-gap dyes for the capture of infrared solar
      photons. Herein, we report two donor-acceptor organic dyes, C294 and C295, with a
      polycyclic heteroaromatic unit, 6,11-dihydrothieno[3',2':8,9]chryseno[10,11,12,1
      bcdefg]carbazole (TCC), as the central module of the electron donor, and
      ethylbenzothiadiazole-benzioc acid as the electron acceptor. The interfacial
      charge recombination was successfully mitigated by introducing an additional
      branched aliphatic chain in C295. Furthermore, the O???S nonbonding interaction
      between the oxygen atom of the alkoxy group and the sulfur atom of the thiophene
      in C295 controlled the conformation of C295, resulting in a narrow energy-gap.
      Time-resolved spectroscopic measurements on C294 and the model dye C272 indicated
      that the elevation of the HOMO energy level decreased the kinetics and yield of
      hole injection owing to a reduction in the driving force and that the shortened
      excited-state lifetime caused by the narrowing of the energy gap was unfavorable
      for electron injection. By fine tuning the composition of the electrolyte, C294
      and C295 eventually achieved high power conversion efficiencies of 11.5 % and
      12.4 %, respectively, under full sunlight of air mass 1.5 global conditions.

PMID- 29570954
TI  - Antigen I/II mediates interactions between Streptococcus mutans and Candida
      albicans.
AB  - Streptococcus mutans and Candida albicans are frequently co-isolated from dental
      plaque of children with early childhood caries (ECC) and are only rarely found in
      children without ECC, suggesting that these species interact in a manner that
      contributes to the pathogenesis of ECC. Previous studies have demonstrated that
      glucans produced by S. mutans are crucial for promoting the formation of biofilm
      and cariogenicity with C. albicans; however, it is unclear how non-glucan S.
      mutans biofilm factors contribute to increased biofilm formation in the presence
      of C. albicans. In this study we examined the role of S. mutans antigen I/II in
      two-species biofilms with C. albicans, and determined that antigen I/II is
      important for the incorporation of C. albicans into the two-species biofilm and
      is also required for increased acid production. The interaction is independent of
      the proteins Als1 and Als3, which are known streptococcal receptors of C.
      albicans. Moreover, antigen I/II is required for the colonization of both S.
      mutans and C. albicans during co-infection of Drosophila melanogaster in vivo.
      Taken together, these results demonstrate that antigen I/II mediates the increase
      of C. albicans numbers and acid production in the two-species biofilm,
      representing new activities associated with this known S. mutans adhesin.

PMID- 29570956
TI  - Exposing migratory sparrows to Plasmodium suggests costs of resistance, not
      necessarily of infection itself.
AB  - Migratory birds move through multiple habitats and encounter a diverse suite of
      parasites. This raises concern over migrants' role in transporting infectious
      disease between breeding and wintering grounds, and along migratory flyways.
      Trade-offs between flight and immune defenses could interfere with infected
      individuals' migratory timing and success, potentially affecting infection
      dynamics. However, experimental evidence that parasitic infection affects
      migratory preparation or timing remains scant. We hypothesized that birds
      encountering hematozoan parasites shortly before migration incur physical costs
      (reduced body condition) and behavioral costs (delayed migration), due to the
      infection itself and/or to the demands of mounting an immune response. We
      experimentally inoculated song sparrows (Melospiza melodia) with Plasmodium
      shortly before fall migration. We monitored infection and body composition for 2
      weeks after inoculation, and used radiotelemetry to track timing of migratory
      departure for another 7 weeks after release. Inoculated individuals that resisted
      infection had lower lean mass 12 days post exposure, relative to controls and
      infected individuals. This suggests trade-offs between body composition and
      immune defenses that might reduce migration success of resistant individuals.
      Despite group differences in body composition prior to release, we did not detect
      significant differences in timing of migration departure several weeks later.
      Thus, malarial infection did not appear to incur detectable costs to body
      composition or to migratory timing, at least when exposure occurs several weeks
      before migration. This study is novel considering not only the costs of
      infection, but also the costs of resisting infection, in an experimental context.

PMID- 29570955
TI  - Human pancreatic alpha- to beta-cell area ratio increases after type 2 diabetes
      onset.
AB  - AIMS/INTRODUCTION: Pancreatic alpha-cell area and the alpha- to beta-cell area
      ratio (alpha/beta) might be associated with glucose tolerance. The aim was to
      clarify how these histological parameters change as glucose tolerance
      deteriorates. MATERIALS AND METHODS: We analyzed pancreatic tissues obtained from
      pancreatectomies of 43 patients. We evaluated the relationships between alpha
      cell area or the alpha/beta and various clinical parameters. Additionally, we
      analyzed alpha-cell proliferation and the expression patterns of various
      pancreatic transcription factors. RESULTS: The alpha/beta in individuals with
      longstanding (previously diagnosed) type 2 diabetes (0.36 +/- 0.12) was higher
      than that in those with normal glucose tolerance (0.18 +/- 0.10; P < 0.01),
      impaired glucose tolerance (0.17 +/- 0.12; P < 0.05) and newly diagnosed diabetes
      (0.17 +/- 0.12; P < 0.05). In all participants, glycated hemoglobin (HbA1c)
      correlated with relative alpha-cell area (P = 0.010). Diabetes duration (P =
      0.004), HbA1c (P < 0.001) and plasma glucose levels (P = 0.008) were
      significantly correlated with the alpha/beta in single regression analyses, and
      diabetes duration was the only independent and significant determinant in
      stepwise multiple regression analyses (P = 0.006). The alpha-cell Ki67-positive
      ratio in patients with HbA1c >=6.5% was significantly higher than that in
      patients with HbA1c <6.5% (P = 0.022). We identified beta-cells that expressed
      aristaless-related homeobox and alpha-cells that did not express aristaless
      related homeobox at all glucose tolerance stages. Aristaless-related homeobox and
      NK homeobox 6.1 expression patterns varied in insulin and glucagon double
      positive cells. CONCLUSIONS: The pancreatic alpha/beta increases after type 2
      diabetes onset and correlates with diabetes duration. This change might occur
      through alpha-cell proliferation and phenotypic changes in pancreatic endocrine
      cells.

PMID- 29570957
TI  - Sensitive Leptospira DNA detection using tapered optical fiber sensor.
AB  - This paper presents the development of tapered optical fiber sensor to detect a
      specific Leptospira bacteria DNA. The bacteria causes Leptospirosis, a deadly
      disease but with common early flu-like symptoms. Optical single mode fiber (SMF)
      of 125 MUm diameter is tapered to produce 12 MUm waist diameter and 15 cm length.
      The novel DNA-based optical fiber sensor is functionalized by incubating the
      tapered region with sodium hydroxide (NaOH), (3-Aminopropyl) triethoxysilane and
      glutaraldehyde. Probe DNA is immobilized onto the tapered region and subsequently
      hybridized by its complementary DNA (cDNA). The transmission spectra of the DNA
      based optical fiber sensor are measured in the 1500 to 1600 nm wavelength range.
      It is discovered that the shift of the wavelength in the SMF sensor is linearly
      proportional with the increase in the cDNA concentrations from 0.1 to 1.0 nM. The
      sensitivity of the sensor toward DNA is measured to be 1.2862 nm/nM and able to
      detect as low as 0.1 fM. The sensor indicates high specificity when only minimal
      shift is detected for non-cDNA testing. The developed sensor is able to
      distinguish between actual DNA of Leptospira serovars (Canicola and Copenhageni)
      against Clostridium difficile (control sample) at very low (femtomolar) target
      concentrations.

PMID- 29570958
TI  - Pleurothotonus (Pisa syndrome) Induced by an Association of Clozapine and
      Mirabegron.

PMID- 29570960
TI  - Impact of Political Rhetoric on Mental Health: A Case Report of First-Episode
      Psychosis After the 2017 US Presidential Inauguration.

PMID- 29570959
TI  - Galantamine-Memantine Combination for Cognitive Impairments Due to
      Electroconvulsive Therapy, Traumatic Brain Injury, and Neurologic and Psychiatric
      Disorders: Kynurenic Acid and Mismatch Negativity Target Engagement.
AB  - Cognitive impairments due to electroconvulsive therapy (ECT), traumatic brain
      injury (TBI), and neurologic and psychiatric disorders are prevalent. Cholinergic
      and glutamatergic pathways, alpha-7 nicotinic acetylcholine (alpha-7nACh)
      receptor, and N-methyl-d-aspartate (NMDA) receptor are potential pathophysiologic
      mechanisms in all of these conditions. Galantamine not only is an
      acetylcholinesterase inhibitor but has a dual mode of action as a alpha-7nACh
      receptor modulator as well. Memantine is a noncompetitive NMDA receptor
      antagonist. Galantamine and memantine are approved by the US Food and Drug
      Administration (FDA) for the treatment of Alzheimer's disease (AD). Galantamine
      and memantine have shown efficacy for the treatment of ECT- and TBI-induced
      cognitive impairments. The kynurenine pathway (KP) metabolites are associated
      with ECT- and TBI-induced cognitive impairments and several neurologic and
      psychiatric disorders. Kynurenic acid (KYNA) is an antagonist to the alpha-7nACh
      and NMDA receptors. The galantamine-memantine combination has been shown to
      modulate several KP metabolites in schizophrenia, thereby improving several
      cognitive domains. There are no FDA-approved treatments for ECT-induced cognitive
      impairments or for cognitive impairments in neurologic and psychiatric disorders
      except AD. This article is timely because the pharmacology of cognition as a
      panacea for neuropsychiatric diseases was recently published. Hence, randomized
      controlled trials are warranted with this combination in these diseases, with
      KYNA and mismatch negativity as novel target engagement. Future positive studies
      may lead to standard of care, which is likely to significantly improve socio
      occupational functioning.

PMID- 29570961
TI  - Charles Bonnet Syndrome in a Geriatric Female Patient: A Case Report.

PMID- 29570962
TI  - Confidential Survey Into Southwestern Ontario Suicide: Implication for Primary
      Care Practice.
AB  - Objective: To describe sociodemographic and clinical characteristics of suicide
      decedents and to explore the pattern of clinical and suicide risk assessment in
      primary care settings. Methods: A 3-year case series of consecutive suicides
      (January 1, 2012, to December 31, 2014) in Southwestern Ontario, Canada,
      identified by the Office of the Chief Coroner of Ontario and Ontario Forensic
      Pathology Service (OCC/OFPS) was conducted. Clinicians who provided care to
      suicide decedents completed a confidential suicide questionnaire offered online
      through a secured portal or by hardcopy. Results: A total of 476 suicide cases
      were analyzed using data extracted from the OCC/OFPS files or provided by
      clinicians who had completed the survey. Hanging (42.8%) was the most common
      method of suicide, followed by self-poisoning (17.9%). More than half of the
      decedents (51.8%) used psychotropic medications, and 29.4% used opiates to self
      poison. Typically, these self-poisonings involved prescribed medications (70.6%).
      Over two-thirds (67.4%) of suicide decedents had consulted their primary care
      physician prior to their deaths, and 63.6% had been seen by a physician within 28
      days of their death. Suicide risk assessments were reportedly conducted in 87.1%
      of these visits. Of those who were assessed, the immediate risk of suicide was
      deemed to be absent in 39.8%, low in 50.0%, moderate in 8.3%, and high in only
      1.9%. Conclusion: The findings from this confidential survey may be important for
      the formulation of recommendations that could improve suicide prevention in
      primary care practice.

PMID- 29570963
TI  - Computer-Assisted Cognitive-Behavior Therapy for Depression in Primary Care:
      Systematic Review and Meta-Analysis.
AB  - Objective: To examine evidence for the effectiveness of computer-assisted
      cognitive-behavior therapy (CCBT) for depression in primary care and assess the
      impact of therapist-supported CCBT versus self-guided CCBT. Methods: A search for
      randomized studies of CCBT compared to control groups for treating depression in
      primary care settings was conducted using Ovid MEDLINE, PsycINFO, PubMed, and
      Scopus. We extracted the following information from the studies that met
      inclusion criteria: mean depression rating scale scores before and after
      treatment, number of patients, type of control group and CCBT program, therapist
      support time and method of support, and treatment completion rate. Meta-analyses
      compared differences between posttreatment mean scores in each condition, as well
      as mean scores at follow-up. Study quality and possible bias also were assessed.
      Results: Eight studies of CCBT for depression in primary care met inclusion
      criteria. The overall effect size was g = 0.258, indicating a small but
      significant advantage for CCBT over control conditions. Therapist support was
      provided in 4 of the 8 studies. The effect size for therapist-supported CCBT was
      g = 0.372-a moderate effect. However, the effect size for self-guided CCBT was g
      = 0.038, indicating little effect. Conclusions: Implementation of therapist
      supported CCBT in primary care settings could enhance treatment efficiency,
      reduce cost, and improve access to effective treatment for depression. However,
      evidence to date suggests that self-guided CCBT offers no benefits over usual
      primary care.

PMID- 29570964
TI  - Motivational Interviewing: Overcoming Disparities in Pharmacotherapy Engagement.

PMID- 29570965
TI  - Can Aripiprazole Worsen Psychosis in Schizophrenia? A Meta-Analysis of Double
      Blind, Randomized, Controlled Trials.
AB  - BACKGROUND: Numerous case reports have reported psychotic worsening when
      switching to or adding aripiprazole in patients with schizophrenia. The risk of
      psychotic worsening related to aripiprazole was evaluated through a systematic
      review and meta-analysis. DATA SOURCES: MEDLINE, Embase, and Cochrane Central
      Register of Controlled Trials were systematically searched using the following
      keywords: (schizophr* or schizoaff*) AND aripiprazole, with a limitation of
      randomized controlled trial and English language (last search: September 9, 2016)
      by the authors in an independent fashion. STUDY SELECTION: Double-blind,
      randomized, controlled trials involving a switch to or addition of aripiprazole
      in schizophrenia spectrum disorders were selected by the authors in an
      independent fashion. A total of 22 studies (13 switching and 9 adding studies)
      involving 5,769 patients that met eligibility criteria were identified and
      included in the meta-analysis. DATA EXTRACTION: Number of patients who
      experienced psychotic worsening, agitation, or anxiety as well as those who
      discontinued the study due to all causes, lack of efficacy, or adverse events
      were extracted. RESULTS: Psychotic worsening was reported as an adverse event in
      all studies. No significant difference in the risk of psychotic worsening was
      found between switching to aripiprazole and switching to another antipsychotic
      (RR = 1.17, 95% CI = 0.97-1.42, P = .10); however, switching to aripiprazole was
      related to a significantly greater risk of study discontinuation due to lack of
      efficacy (RR = 1.46, 95% CI = 1.10-1.93, P = .009). Lack of data resulted in no
      conclusive results as to clinical risks of adding aripiprazole. CONCLUSIONS:
      Findings suggest that there is no direct evidence that a switch to aripiprazole
      is related to risk of psychotic worsening in participants in clinical trials,
      although a switch to aripiprazole may be associated with a higher risk of study
      discontinuation due to lack of efficacy.

PMID- 29570966
TI  - Is Cannabis Use Associated With Increased Risk of Cigarette Smoking Initiation,
      Persistence, and Relapse? Longitudinal Data From a Representative Sample of US
      Adults.
AB  - OBJECTIVE: The current study prospectively investigated the relationship between
      cannabis use and cigarette smoking initiation, persistence, and relapse during a
      3-year period among adults in the United States. METHODS: Analyses included
      respondents who completed Waves 1 (2001-2002) and 2 (2004-2005) of the National
      Epidemiologic Survey on Alcohol and Related Conditions and responded to questions
      about cannabis use and smoking status (n = 34,639). Multivariable logistic
      regression models were used to calculate the odds of cigarette use at Wave 2
      among Wave 1 daily smokers, nondaily smokers, former smokers, and nonsmokers by
      Wave 1 cannabis use. RESULTS: In unadjusted analyses, Wave 1 cannabis use was
      associated with increased odds of Wave 2 daily and nondaily smoking for Wave 1
      nonsmokers (daily OR = 2.90; 95% CI, 2.10-4.00; nondaily OR = 4.45; 95% CI, 3.97
      5.00) and Wave 2 relapse to daily and nondaily smoking for Wave 1 former smokers
      (daily OR = 4.18, 95% CI, 3.01-5.81; nondaily OR = 5.24; 95% CI, 3.74-7.34). Wave
      1 cannabis use was associated with decreased odds of Wave 2 smoking cessation for
      Wave 1 daily cigarette smokers (OR = 0.57; 95% CI, 0.51-0.64). The associations
      remained significant for daily smoking initiation (OR = 1.43; 95% CI, 1.06-1.93),
      daily smoking relapse (OR = 1.47; 95% CI, 1.00-2.16), and smoking cessation (OR =
      0.77; 95% CI, 0.69-0.87) after adjusting for demographics and psychiatric
      disorders. Associations remained significant for nondaily smoking initiation (OR
      = 1.85; 95% CI, 1.59-2.16) and nondaily smoking relapse (OR = 1.63; 95% CI, 1.05
      2.54) after adjusting for these covariates as well as for alcohol and substance
      use disorders. CONCLUSIONS: Cannabis use was associated with increased initiation
      of, persistence of, and relapse to cigarette smoking. Additional attention to
      cannabis use in tobacco control efforts and in clinical settings aimed at
      reducing cigarette smoking and smoking-related negative consequences may be
      warranted.

PMID- 29570967
TI  - Successful Treatment of Catatonia with Methylphenidate in a 25-Year-Old Patient
      With Schizophrenia.

PMID- 29570968
TI  - The Communication Gap Between the Medical System and Community Resources for
      Dementia-Related Behavioral Symptom Management: Family Caregiver Perspectives.
AB  - Objective: To examine family caregiver perspectives on cooperative communication
      surrounding pharmacologic and nonpharmacologic resources for the treatment of
      dementia-related behavioral symptoms. Methods: Personal narrative interviews were
      conducted by the primary investigator with 13 family caregivers from October 2014
      to April 2015. The recorded interviews were then transcribed and coded. Models
      detailing the caregivers' resource utilization in regard to behavioral symptom
      management were produced for each participant and then summarized on the basis of
      recurring themes. Results: There is a significant gap in the coordination and
      communication between physician services and caregiver community resources to aid
      in the behavioral management of family members with dementia. Physicians tend to
      rely on pharmacologic management independent of community resources and did not
      seem to be integrated or involved with recommendations from community resources.
      Conclusions: Better integration of caregiver resources is necessary to help
      caregivers in the management of dementia-related behavioral symptoms.

PMID- 29570969
TI  - Tardive Dyskinesia: Recognition, Patient Assessment, and Differential Diagnosis.
AB  - Tardive dyskinesia (TD) is an involuntary movement disorder associated with
      antipsychotic treatment. Because of the serious and potentially irreversible
      nature of TD, accurate diagnosis is crucial. However, diagnosing TD can be
      challenging, since the subtle and often fluctuating symptoms can be easily
      mistaken for symptoms of mental illness or other side effects. Although the risk
      of developing TD in relation to treatment with second-generation antipsychotics
      is lower than that associated with first-generation antipsychotics, the risk
      still exists and may be greater than once believed. Clinicians prescribe
      antipsychotics for a variety of illnesses and may underestimate the possibility
      of a patient developing TD, thus missing early signs of the disorder. In this
      ACADEMIC HIGHLIGHTS, experts review the prevalence, phenomenology, risk factors,
      and impact of TD, illustrated by case examples, and provide valuable clinical
      information to guide early recognition and accurate diagnosis. From the
      Department of Psychiatry, Texas Tech University Health Sciences Center Medical
      School, Midland (Dr Jain); the Department of Psychiatry and Molecular Medicine,
      Hofstra Northwell School of Medicine, Hempstead, and the Department of
      Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York, and the Department
      of Child and Adolescent Psychiatry, Charite Universitatsmedizin, Berlin, Germany
      (Dr Correll) mask.

PMID- 29570970
TI  - Sources of Prescription Medication Misuse Among Young Adults in the United
      States: The Role of Educational Status.
AB  - OBJECTIVE: This study examined prescription drug misuse (PDM), sources of PDM,
      and substance use disorder (SUD) symptoms as a function of educational status
      among US young adults based on a large nationally representative sample. METHODS:
      Data from the 2009-2014 National Survey on Drug Use and Health came from a sample
      of 106,845 young adults aged 18-25 years. Respondents were categorized by
      educational status and PDM, sources of PDM, other substance use, and SUD
      symptoms, with analyses performed separately for prescription opioids,
      stimulants, and sedatives/tranquilizers. RESULTS: Prescription opioid (past-year:
      11.9%) and sedative/tranquilizer (past-year: 5.8%) misuse were most prevalent
      among young adults not attending college, especially among high school dropouts.
      In contrast, full-time college students and college graduates had the highest
      rates of prescription stimulant misuse (past-year: 4.3% and 3.9%, respectively).
      Obtaining prescription medications from friends/relatives for free was the most
      common source of PDM, especially among college students/graduates. Prescription
      drug misusers who obtained medications from theft/fake prescriptions, purchases,
      or multiple sources were more likely to report past-year SUDs and had the most
      severe overall risk profile of concurrent substance use and SUD. More than 70% of
      past-month prescription drug misusers who reported multiple sources for PDM had
      at least 1 past-year SUD. CONCLUSIONS: Sources of PDM vary by educational status
      among US young adults, and the college environment is associated with sharing
      prescription medications. Clinicians can help assess an individual's risk for SUD
      by determining whether the individual engaged in PDM and the source of
      prescription medication the individual is misusing.

PMID- 29570971
TI  - Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients
      Treated With Antidepressants in an Ambulatory Setting.
AB  - OBJECTIVE: Drug-metabolizing enzymes (DMEs), such as cytochrome P450 (CYP)
      enzymes, and transporters have emerged as major determinants of variability in
      drug metabolism and response. This study investigated the association between CYP
      and P-glycoprotein activities and plasma antidepressant concentration in an
      outpatient clinical setting. Secondary outcomes were antidepressant efficacy and
      tolerance. We also describe phenotypes in patients treated with antidepressants
      and evaluate the tolerance of a minimally invasive phenotyping approach. METHODS:
      From January 2015 to August 2015, 64 patients on a stable antidepressant regimen
      underwent a simultaneous assessment of steady-state antidepressant concentration
      and DME (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A) and P-glycoprotein
      transporter activity using a cocktail phenotyping approach. Psychiatric diagnoses
      were in accordance with DSM-5. RESULTS: We observed a high proportion of subjects
      (> 20%) with reduced activity of CYP2C19, CYP2D6, CYP3A4, and P-glycoprotein. As
      expected, higher CYP activity for major metabolic pathways was associated with
      lower concentration of the parent compound (CYP2C19 and escitalopram, P = .025;
      CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .001), higher
      concentration of the metabolite (CYP2D6 and O-desmethylvenlafaxine, P = .007),
      and higher metabolite-to-parent drug ratio (CYP2C19 and escitalopram, P = .03;
      CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .048; CYP2B6 and
      sertraline, P = .006). Phenotyping also highlighted the relevance of a minor
      metabolic pathway for venlafaxine (CYP3A4). Insufficient response and adverse
      reactions to antidepressants were not significantly associated with plasma
      antidepressant concentration, DME, or P-glycoprotein activity. Tolerance of the
      phenotypic test in ambulatory settings was found to be excellent. CONCLUSIONS:
      The phenotypic assessment of DMEs and a transporter is a valuable, well-tolerated
      method to explore the interindividual variability in drug disposition in clinical
      settings. The method is able to account for the inhibitory activity of
      antidepressants themselves and for polymedication, which is frequent in this
      population of refractory depressed patients. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT02438072.

PMID- 29570972
TI  - Shotgun Analysis of Diacylglycerols Enabled by Thiol-ene Click Chemistry.
AB  - Diacylglycerols (DAGs) are a subclass of neutral lipids actively involved in cell
      signaling and metabolism. Alteration in DAG metabolism has been associated with
      onset and progression of several human-related diseases. The structural diversity
      of DAGs and their low concentrations in biological samples call for the
      development of methods that are capable of sensitive identification and
      quantitation of each DAG species as well as rapid profiling when a biochemical
      pathway is perturbed. In this work, the thiol-ene click chemistry has been
      employed to introduce a charge-tag, namely, cysteamine (CA), at a carbon-carbon
      double bond (C?C) of unsaturated DAGs. This one-pot photochemical derivatization
      is fast (within 1 min), universal (monotagging) for DAGs varying in fatty acyl
      chain lengths and the number of C?Cs, and suitable for small sample volume (e.g.,
      1-50 MUL plasma). Because of the presence of the amine group in CA, tagged DAGs
      showed at least 10 times increase in response to electrospray ionization as
      compared to conventional ammonium adduct formation. Low-energy collision-induced
      dissociation of CA tagged DAGs allowed confident assignment of fatty acyl
      composition. A neutral loss scan based on characteristic 95 Da loss (a combined
      loss of CA and H2O) of tagged DAGs has been established as a sensitive means for
      unsaturated DAG detection (limit of detection = 100 pM) and quantitation from
      mixtures. The analytical utility of CA tagging was demonstrated by shotgun
      analysis of unsaturated DAGs in human plasma, including samples from type 2
      diabetes mellitus patients.

PMID- 29570974
TI  - Online Monitoring of Intraoperative Exhaled Propofol by Acetone-Assisted Negative
      Photoionization Ion Mobility Spectrometry Coupled with Time-Resolved Purge
      Introduction.
AB  - Online monitoring of exhaled propofol concentration is important for anesthetists
      to provide adequate anesthesia as propofol concentrations in plasma and breath
      are correlated reasonably well. Exhaled propofol could be detected by 63Ni ion
      mobility spectrometry in negative ion mode; however, the radioactivity of 63Ni
      source restricts its clinical application due to safety, environmental, and
      regulatory concerns. An acetone-assisted negative photoionization ion mobility
      spectrometer (AANP-IMS) using a side-mounted vacuum ultraviolet (VUV) lamp in the
      unidirectional (UD) flow mode was developed for sensitive measurement of exhaled
      propofol by producing a high percentage of O2-(H2O) n. An adsorption sampling and
      time-resolved purge introduction system was developed to eliminate the
      interference of residual inhaled anesthetic sevoflurane based on their different
      adsorptions between propofol and sevoflurane on the inwall of the fluorinated
      ethylene propylene (FEP) sample loop. The effects of the inner diameter and the
      length of the sample loop on the signal intensity of propofol and the time
      resolution between propofol and sevoflurane were theoretically and experimentally
      investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive
      measurement of exhaled propofol with a response time of 4 s, a linear response
      range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection
      (LOD) of 60 pptv, and the quantification of propofol was not influenced by the
      change of the sevoflurane concentration. Finally, the performance of monitoring
      exhaled propofol during surgery was demonstrated on a patient undergoing
      laparoscopic distal pancreatectomy combined with cholecystectomy.

PMID- 29570973
TI  - Global Distribution of Human-Associated Fecal Genetic Markers in Reference
      Samples from Six Continents.
AB  - Numerous bacterial genetic markers are available for the molecular detection of
      human sources of fecal pollution in environmental waters. However, widespread
      application is hindered by a lack of knowledge regarding geographical stability,
      limiting implementation to a small number of well-characterized regions. This
      study investigates the geographic distribution of five human-associated genetic
      markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal
      wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants
      (750-4 400 000 population equivalents) from 13 countries spanning six continents.
      In addition, genetic markers were tested against 280 human and nonhuman fecal
      samples from domesticated, agricultural and wild animal sources. Findings
      revealed that all genetic markers are present in consistently high concentrations
      in raw (median log10 7.2-8.0 marker equivalents (ME) 100 mL-1) and biologically
      treated wastewater samples (median log10 4.6-6.0 ME 100 mL-1) regardless of
      location and population. The false positive rates of the various markers in
      nonhuman fecal samples ranged from 5% to 47%. Results suggest that several
      genetic markers have considerable potential for measuring human-associated
      contamination in polluted environmental waters. This will be helpful in water
      quality monitoring, pollution modeling and health risk assessment (as
      demonstrated by QMRAcatch) to guide target-oriented water safety management
      across the globe.

PMID- 29570975
TI  - In Situ Observation of Chymotrypsin Catalytic Activity Change Actuated by
      Nonheating Low-Frequency Magnetic Field.
AB  - Magnetomechanical modulation of biochemical processes is a promising instrument
      for bioengineering and nanomedicine. This work demonstrates two approaches to
      control activity of an enzyme, alpha-chymotrypsin immobilized on the surface of
      gold-coated magnetite magnetic nanoparticles (GM-MNPs) using a nonheating low
      frequency magnetic field (LF MF). The measurement of the enzyme reaction rate was
      carried out in situ during exposure to the magnetic field. The first approach
      involves alpha-chymotrypsin-GM-MNPs conjugates, in which the enzyme undergoes
      mechanical deformations with the reorientation of the MNPs under LF MF (16-410 Hz
      frequency, 88 mT flux density). Such mechanical deformations result in
      conformational changes in alpha-chymotrypsin structure, as confirmed by infrared
      spectroscopy and molecular modeling, and lead to a 63% decrease of enzyme initial
      activity. The second approach involves an alpha-chymotrypsin-GM-MNPs/trypsin
      inhibitor-GM-MNPs complex, in which the activity of the enzyme is partially
      inhibited. In this case the reorientation of MNPs in the field leads to
      disruption of the enzyme-inhibitor complex and an almost 2-fold increase of
      enzyme activity. The results further demonstrate the utility of magnetomechanical
      actuation at the nanoscale for the remote modulation of biochemical reactions.

PMID- 29570976
TI  - Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease
      Heterogeneity.
AB  - Hepatocellular lipid accumulation characterizes nonalcoholic fatty liver disease
      (NAFLD). However, the types of lipids associated with disease progression are
      debated, as is the impact of their localization. Traditional lipidomics analysis
      using liver homogenates or plasma dilutes and averages lipid concentrations, and
      does not provide spatial information about lipid distribution. We aimed to
      characterize the distribution of specific lipid species related to NAFLD severity
      by performing label-free molecular analysis by mass spectrometry imaging (MSI).
      Fresh frozen liver biopsies from obese subjects undergoing bariatric surgery ( n
      = 23) with various degrees of NAFLD were cryosectioned and analyzed by matrix
      assisted laser desorption/ionization (MALDI)-MSI. Molecular identification was
      verified by tandem MS. Tissue sections were histopathologically stained,
      annotated according to the Kleiner classification, and coregistered with the MSI
      data set. Lipid pathway analysis was performed and linked to local proteome
      networks. Spatially resolved lipid profiles showed pronounced differences between
      nonsteatotic and steatotic tissues. Lipid identification and network analyses
      revealed phosphatidylinositols and arachidonic acid metabolism in nonsteatotic
      regions, whereas low-density lipoprotein (LDL) and very low-density lipoprotein
      (VLDL) metabolism was associated with steatotic tissue. Supervised and
      unsupervised discriminant analysis using lipid based classifiers outperformed
      simulated analysis of liver tissue homogenates in predicting steatosis severity.
      We conclude that lipid composition of steatotic and nonsteatotic tissue is highly
      distinct, implying that spatial context is important for understanding the
      mechanisms of lipid accumulation in NAFLD. MSI combined with principal component
      linear discriminant analysis linking lipid and protein pathways represents a
      novel tool enabling detailed, comprehensive studies of the heterogeneity of
      NAFLD.

PMID- 29570977
TI  - Cystamine and Disulfiram Inhibit Human Transglutaminase 2 via an Oxidative
      Mechanism.
AB  - The catalytic activity of transglutaminase 2 (TG2), a ubiquitously expressed
      mammalian enzyme, is regulated by multiple post-translational mechanisms. Because
      elevated activity of TG2 in the extracellular matrix is associated with organ
      specific diseases such as celiac disease and renal fibrosis, there is growing
      therapeutic interest in inhibitors of this enzyme. Cystamine, a symmetric
      disulfide compound, is one of the earliest reported TG2 inhibitors. Despite its
      widespread use as a tool compound to block TG2 activity in vitro and in vivo, its
      mechanism of action has remained unclear. Here, we demonstrate that cystamine
      irreversibly inhibits human TG2 ( kinh/ Ki = 1.2 mM-1 min-1) via a mechanism
      fundamentally distinct from those proposed previously. Through mass spectrometric
      disulfide mapping and site-directed mutagenesis, we show that cystamine promotes
      the formation of a physiologically relevant disulfide bond between Cys370 and
      Cys371 that allosterically abrogates the catalytic activity of human TG2. This
      discovery led us to evaluate clinically useful thiol -> disulfide oxidants for
      TG2 inhibitory activity. It is demonstrated that disulfiram, a relatively safe
      oral thiuram disulfide, is a fairly potent TG2 inhibitor ( kinh/ Ki = 8.3 mM-1
      min-1) and may therefore provide a practical tool for clinically validating this
      emerging therapeutic target in intestinal disorders such as celiac disease.

PMID- 29570978
TI  - Direct Detection of Small n-Alkanes at Sub-ppbv Level by Photoelectron-Induced
      O2+ Cation Chemical Ionization Mass Spectrometry at kPa Pressure.
AB  - Direct mass spectrometric measurements of saturated hydrocarbons, especially
      small n-alkanes, remains a great challenge because of low basicity and lack of
      ionizable functional groups. In this work, a novel high-pressure photoelectron
      induced O2+ cation chemical ionization source (HPPI-OCI) at kPa based on a 10.6
      eV krypton lamp was developed for a time-of-flight mass spectrometer (TOFMS).
      High-intensity O2+ reactant ions were generated by photoelectron ionization of
      air molecules in the double electric field ionization region. The quasi-molecular
      ions, [M-H]+, of C3-C6 n-alkanes, gradually dominated in the mass spectra when
      the ion source pressure was elevated from 88 to 1080 Pa, with more than 3 orders
      of magnitude improvement in signal intensity. As a result, the achieved limits of
      detection were lowered to 0.14, 0.11, 0.07, and 0.1 ppbv for propane, n-butane, n
      pentane, and n-hexane, respectively. The performance of the HPPI-OCI TOFMS was
      first demonstrated by analysis of exhaled small n-alkanes from healthy smokers
      and nonsmokers. Then the concentration variations of exhaled small n-alkanes of
      four healthy volunteers were analyzed after alcohol consumption to explore the
      alcohol-hepatoxicity-related oxidative stress. In summary, this work provides new
      insights for controlling the O2+-participating chemical ionization by adjusting
      the ion source pressure and develops a novel direct mass spectrometric method for
      sensitive measurements of mall n-alkanes.

PMID- 29570980
TI  - Identifying Fenton-Reacted Trimethoprim Transformation Products Using
      Differential Mobility Spectrometry.
AB  - A transformation product of trimethoprim, a contaminant of emerging concern in
      the environment, is generated using an electro-assisted Fenton reaction and
      analyzed using differential mobility spectrometry (DMS) in combination with MS/MS
      techniques and quantum chemical calculations to develop a rapid method for
      identification. DMS is used as a prefilter to separate positional isomers prior
      to subsequent identification by mass spectrometric analyses. Collision induced
      dissociation of each DMS separated species is used to reveal fragmentation
      patterns that can be correlated to specific isomer structures. Analysis of the
      experimental data and supporting quantum chemical calculations show that
      methylene-hydroxylated and methoxy-containing phenyl ring hydroxylated
      transformation products are observed. The proposed methodology outlines a high
      throughput technique to determine transformation products of small molecules
      accurately, in a short time and requiring minimal sample concentrations (<25
      ng/mL).

PMID- 29570979
TI  - Sensitivity of Ambient Atmospheric Formaldehyde and Ozone to Precursor Species
      and Source Types Across the United States.
AB  - Formaldehyde (HCHO) is an important air pollutant from both an atmospheric
      chemistry and human health standpoint. This study uses an instrumented
      photochemical Air Quality Model, CMAQ-DDM, to identify the sensitivity of HCHO
      concentrations across the United States (U.S.) to major source types and
      hydrocarbon speciation. In July, biogenic sources of hydrocarbons contribute the
      most (92% of total hydrocarbon sensitivity), split between isoprene and other
      alkenes. Among anthropogenic sources, mobile sources of hydrocarbons and nitrogen
      oxides (NO x) dominate. In January, HCHO is more sensitive to anthropogenic
      hydrocarbons than biogenic sources, especially mobile sources and residential
      wood combustion (36% of national hydrocarbon sensitivity). While ozone (O3) is
      three times more sensitive to NO x than hydrocarbons across most areas of the
      U.S., HCHO is six times more sensitive to hydrocarbons than NO x, largely due to
      sensitivity to biogenic precursors and the importance of low-NO x chemistry. In
      winter, both HCHO and O3 show negative sensitivity to NO x (increases with the
      removal of NO x), although O3 increases are larger. Relative sensitivities do not
      change substantially across different regions of the country.

PMID- 29570981
TI  - Discovery of a Pederin Family Compound in a Nonsymbiotic Bloom-Forming
      Cyanobacterium.
AB  - The pederin family includes a number of bioactive compounds isolated from
      symbiotic organisms of diverse evolutionary origin. Pederin is linked to beetle
      induced dermatitis in humans, and pederin family members possess potent antitumor
      activity caused by selective inhibition of the eukaryotic ribosome. Their
      biosynthesis is accomplished by a polyketide/nonribosomal peptide synthetase
      machinery employing an unusual trans-acyltransferase mechanism. Here, we report a
      novel pederin type compound, cusperin, from the free-living cyanobacterium
      Cuspidothrix issatschenkoi (earlier Aphanizomenon). The chemical structure of
      cusperin is similar to that of nosperin recently isolated from the lichen
      cyanobiont Nostoc sharing the tehrahydropyran moiety and major part of the linear
      backbone. However, the cusperin molecule is extended by a glycine residue and
      lacks one hydroxyl substituent. Pederins were previously thought to be exclusive
      to symbiotic relationships. However, C. issatschenkoi is a nonsymbiotic
      planktonic organism and a frequent component of toxic water blooms. Cusperin is
      devoid of the cytotoxic activity reported for other pederin family members.
      Hence, our findings raise questions about the role of pederin analogues in
      cyanobacteria and broaden the knowledge of ecological distribution of this group
      of polyketides.

PMID- 29570983
TI  - Survivorship Care Planning for Young Adults After Cancer Treatment: Understanding
      Care Patterns and Patient-Reported Outcomes.
AB  - PURPOSE: Young adult survivors (YAS) of cancer experience late effects of
      treatment similar to older adult survivors (AS). Online health tools such as
      Internet-based survivorship care plans (SCPs) can provide access to information
      about late effects and symptom management, but little is known about SCP patterns
      of use among YAS. METHODS: An Internet-based cross-sectional survey was completed
      over 24 months. Participants were individuals diagnosed with cancer between 18
      and 39 years (YAS, n = 611) or 40-60 years (AS, n = 1742), who were 2-20 years
      postdiagnosis, and who created an Internet-based SCP. Demographics, treatment
      related variables, satisfaction with SCP, communication of SCP, and patient
      reported late effects (fatigue, neurocognitive, sexual, cardiovascular,
      pulmonary, or second cancers) were collected. RESULTS: YAS were primarily female
      (71%), Caucasian (78%), college educated (65%), and generated the SCP without
      assistance (76%). YAS reported satisfaction with content (93%) and shared content
      with providers (71%). A higher proportion of YAS than AS were male (29% vs. 17%,
      p < 0.001), lived internationally (23% vs. 17%, p = 0.003), and endorsed
      oncologist-led survivorship care (47% vs. 41%, p = 0.001). YAS reported concerns
      about neurocognitive performance (56%) and fatigue (50%). Overall, YAS reported
      equivalent or fewer late effects than AS across all domains. CONCLUSIONS: YAS
      report high satisfaction with the online SCP, as well as a high symptom burden,
      although the latter were reported less than for AS.

PMID- 29570982
TI  - Using ramp-incremental VO2 responses for constant-intensity exercise selection.
AB  - Despite compelling evidence to the contrary, the view that oxygen uptake (VO2)
      increases linearly with exercise intensity (e.g., power output, speed) until
      reaching its maximum persists within the exercise physiology literature. This
      viewpoint implies that the VO2 response at any constant intensity is predictable
      from a ramp-incremental exercise test. However, the VO2 versus task-specific
      exercise intensity relationship constructed from ramp-incremental versus constant
      intensity exercise are not equivalent preventing the use of VO2 responses from 1
      domain to predict those of the other. Still, this "linear" translational
      framework continues to be adopted as the guiding principle for aerobic exercise
      prescription and there remains in the sport science literature a lack of
      understanding of how to interpret VO2 responses to ramp-incremental exercise and
      how to use those data to assign task-specific constant-intensity exercise. The
      objectives of this paper are to (i) review the factors that disassociate the VO2
      versus exercise intensity relationship between ramp-incremental and constant
      intensity exercise paradigms; (ii) identify when it is appropriate (or not) to
      use ramp VO2 responses to accurately assign constant-intensity exercise; and
      (iii) illustrate the technical and theoretical challenges with prescribing
      constant-intensity exercise solely on information acquired from ramp-incremental
      tests. Actual VO2 data collected during cycling exercise and VO2 kinetics
      modelling are presented to exemplify these concepts. Possible solutions to
      overcome these challenges are also presented to inform on appropriate intensity
      selection for individual-specific aerobic exercise prescription in both research
      and practical settings.

PMID- 29570984
TI  - Effects of the Green Tea Polyphenol Epigallocatechin-3-Gallate on Glioma: A
      Critical Evaluation of the Literature.
AB  - The review discusses the effects of Epigallocatechin-3-gallate Gallate (EGCG) on
      glioma as a basis for future research on clinical application of EGCG.
      Epidemiological studies on the effects of green tea or EGCG on the risk of glioma
      is inconclusive due to the limited number of studies, the inclusion of all tea
      types in these studies, and the focus on caffeine rather than EGCG. In vivo
      experiments using EGCG monotherapy are inconclusive. Nevertheless, EGCG induces
      cell death, prevents cellular proliferation, and limits invasion in multiple
      glioma cell lines. Furthermore, EGCG enhances the efficacy of anti-glioma
      therapies, including irradiation, temozolomide, carmustine, cisplatin, tamoxifen,
      and TNF-related apoptosis-inducing ligand, but reduces the effect of bortezomib.
      Pro-drugs, co-treatment, and encapsulation are being investigated to enhance
      clinical applicability of EGCG. Mechanisms of actions of EGCG have been partly
      elucidated. EGCG has both anti-oxidant and oxidant properties. EGCG inhibits pro
      survival proteins, such as telomerase, survivin, GRP78, PEA15, and P-gp. EGCG
      inhibits signaling of PDGFR, IGF-1R, and 67LR. EGCG reduces invasiveness of
      cancer cells by inhibiting the activities of various metalloproteinases,
      cytokines, and chemokines. Last, EGCG inhibits some NADPH-producing enzymes, thus
      disturbing redox status and metabolism of glioma cells. In conclusion, EGCG may
      be a suitable adjuvant to potentiate anti-glioma therapies.

PMID- 29570985
TI  - Processed Meat and Risk of Renal Cell and Bladder Cancers.
AB  - We assessed the association of processed meat intake with the risk of renal cell
      carcinoma (RCC) and bladder cancer. We used data from two Italian hospital-based
      case-control studies, including 1,115 RCC cases and 2,582 controls, and 1,417
      bladder cancer cases and 1,732 controls. We calculated odds ratios (ORs) and 95%
      confidence intervals (CIs) with unconditional logistic regression models,
      adjusted for major confounders. The median consumption of processed meat in cases
      and controls was around 2 portions/week (50 g/portion). The ORs for a daily 10 g
      increment of processed meat was 0.89 (95% CI 0.84-0.94) for RCC and 1.00 (95% CI
      0.94-1.06) for bladder cancer. The OR for the highest vs. the lowest consumption
      was 0.80 (95% CI 0.66-0.96) for RCC and 0.98 (95% CI 0.80-1.21) for bladder
      cancer. The ORs were consistent in strata of various covariates. For bladder
      cancer, however, a significant 23% excess risk was found in women (95% CI 1.03
      1.47) for a daily increase of 10 g, significantly heterogeneous from the risk
      recorded in men (OR 0.96, 95% CI 0.90-1.02). The inconsistent results between men
      and women and the absence of association in both sexes combined indicate that the
      apparent association between processed meat and bladder cancer in women is
      unlikely to be causal.

PMID- 29570987
TI  - Role of EGCG in Containing the Progression of Lung Tumorigenesis - A Multistage
      Targeting Approach.
AB  - Lung cancer is a prominent form among various types of cancers, irrespective of
      the sex worldwide. Treatment of lung cancer involves the intensive phase of
      chemotherapy/radiotherapy which is associated with high rate of adverse events.
      There is a need of safe and reliable treatment/adjunctive therapy to apprehend
      the cancer by reducing the undesirable outcome of primary therapy.
      Epigallocatechin-3-gallate (EGCG), which is a potent antioxidant and anticancer
      compound extracted from the plant camellia sinensis has proved to be a novel
      agent to control or reduce lung tumorigenesis by affecting the signaling
      molecules of cell cycle regulation and apoptotic pathways. In vitro studies have
      revealed that EGCG can contain carcinogenesis by altering the molecules involved
      in multiple signal transduction pathways like ERK, VEGF, COX2, NEAT, Ras-GTPase,
      and kinases. The animal studies have also demonstrated effectiveness of EGCG by
      inhibiting various molecular pathways which include AKT, NFkB, MAPK, Bcl/Bax,
      DNMT1, and HIF-1alpha. Various attempts have been made to see the adjunctive role
      of EGCG in human lung cancer. Phase I/II clinical studies have recommended that
      EGCG is quite safe and effective in providing protection against cancer. In this
      review, we will discuss the role of EGCG and its molecular mechanisms in lung
      carcinogenesis.

PMID- 29570986
TI  - AMP-activated Protein Kinase Phosphorylation of Angiotensin-Converting Enzyme 2
      in Endothelium Mitigates Pulmonary Hypertension.
AB  - RATIONALE: Endothelial dysfunction plays an integral role in pulmonary
      hypertension (PH). AMPK (AMP-activated protein kinase) and ACE2 (angiotensin
      converting enzyme 2) are crucial in endothelial homeostasis. The mechanism by
      which AMPK regulates ACE2 in the pulmonary endothelium and its protective role in
      PH remain elusive. OBJECTIVES: We investigated the role of AMPK phosphorylation
      of ACE2 Ser680 in ACE2 stability and deciphered the functional consequences of
      this post-translational modification of ACE2 in endothelial homeostasis and PH.
      METHODS: Bioinformatics prediction, kinase assay, and antibody against phospho
      ACE2 Ser680 (p-ACE2 S680) were used to investigate AMPK phosphorylation of ACE2
      Ser680 in endothelial cells. Using CRISPR-Cas9 genomic editing, we created gain
      of-function ACE2 S680D knock-in and loss-of-function ACE2 knockout (ACE2-/-)
      mouse lines to address the involvement of p-ACE2 S680 and ACE2 in PH. The AMPK-p
      ACE2 S680 axis was also validated in lung tissue from humans with idiopathic
      pulmonary arterial hypertension. MEASUREMENTS AND MAIN RESULTS: Phosphorylation
      of ACE2 by AMPK enhanced the stability of ACE2, which increased Ang (angiotensin)
      1-7 and endothelial nitric oxide synthase-derived NO bioavailability. ACE2 S680D
      knock-in mice were resistant to PH as compared with wild-type littermates. In
      contrast, ACE2-knockout mice exacerbated PH, a similar phenotype found in mice
      with endothelial cell-specific deletion of AMPKalpha2. Consistently, the
      concentrations of phosphorylated AMPK, p-ACE2 S680, and ACE2 were decreased in
      human lungs with idiopathic pulmonary arterial hypertension. CONCLUSIONS:
      Impaired phosphorylation of ACE2 Ser680 by AMPK in pulmonary endothelium leads to
      a labile ACE2 and hence is associated with the pathogenesis of PH. Thus, AMPK
      regulation of the vasoprotective ACE2 is a potential target for PH treatment.

PMID- 29570988
TI  - Frailty and Comorbidities Among Survivors of Adolescent and Young Adult Cancer: A
      Cross-Sectional Examination of a Hospital-Based Survivorship Cohort.
AB  - PURPOSE: Cancer survivors are at increased risk for the early development of age
      related chronic medical conditions compared with peers without a history of
      cancer; however, little is known regarding the burden of these conditions among
      survivors of adolescent and young adult (AYA) cancers. In response, we sought to
      determine the prevalence of specific comorbidities and frailty among AYAs (15-39
      years old at diagnosis) enrolled in a cancer survivorship cohort. METHODS: Using
      a cross-sectional survey of a tertiary medical center-based cancer survivorship
      cohort, we determined the prevalence of specific comorbidities and frailty using
      the survey-based FRAIL assessment. In separate models adjusting for age, we
      estimated prevalence ratios (PRs) for the associations between patient
      characteristics and (1) any comorbidity and (2) frailty or prefrailty using log
      binomial models. RESULTS: We identified 271 AYA cancer survivors, most of whom
      were 30-39 years old at survey (57%). A majority of survivors (n = 163, 60%)
      reported having at least one comorbidity with the most common being depression
      (28%), anxiety (27%), asthma (17%), high cholesterol (15%), and hypertension
      (15%). Of the 184 AYA survivors at least 1 year from cancer diagnosis, 19 (10%)
      were classified as frail and 39 (21%) as prefrail. Survivors who were smokers (PR
      2.0, 95% confidence interval [CI]: 1.16-3.56); obese (PR 1.7, 95% CI: 1.10-2.55);
      uninsured (PR 2.7, 95% CI: 1.63-4.59); or who reported comorbid depression or
      anxiety (PR 2.4, 95% CI: 1.51-3.67) were more likely to be frail or prefrail.
      CONCLUSIONS: The prevalence of frailty and comorbidities is high among AYA cancer
      survivors suggestive of accelerated aging.

PMID- 29570990
TI  - There Will Be Blood Tests.

PMID- 29570989
TI  - Measuring the effect of nurse staffing on patient outcomes: A comment on Kim &
      Bae (2018).

PMID- 29570991
TI  - Opportunities and Challenges in Building a Spatiotemporal Multi-scale Model of
      the Human Pancreatic beta Cell.
AB  - The construction of a predictive model of an entire eukaryotic cell that
      describes its dynamic structure from atomic to cellular scales is a grand
      challenge at the intersection of biology, chemistry, physics, and computer
      science. Having such a model will open new dimensions in biological research and
      accelerate healthcare advancements. Developing the necessary experimental and
      modeling methods presents abundant opportunities for a community effort to
      realize this goal. Here, we present a vision for creation of a spatiotemporal
      multi-scale model of the pancreatic beta-cell, a relevant target for
      understanding and modulating the pathogenesis of diabetes.

PMID- 29570992
TI  - Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and
      H2S Production.
AB  - Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is
      an adaptive response to oxygen/nutrient deprivation orchestrated by vascular
      endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best
      understood trigger of VEGF expression via the transcription factor HIF1alpha.
      Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in
      angiogenesis is poorly characterized. Here, we identified sulfur amino acid
      restriction as a proangiogenic trigger, promoting increased VEGF expression,
      migration and sprouting in ECs in vitro, and increased capillary density in mouse
      skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway
      independent of hypoxia or HIF1alpha. We also identified a requirement for
      cystathionine-gamma-lyase in VEGF-dependent angiogenesis via increased hydrogen
      sulfide (H2S) production. H2S mediated its proangiogenic effects in part by
      inhibiting mitochondrial electron transport and oxidative phosphorylation,
      resulting in increased glucose uptake and glycolytic ATP production.

PMID- 29570993
TI  - A Neural Circuit for the Suppression of Pain by a Competing Need State.
AB  - Hunger and pain are two competing signals that individuals must resolve to ensure
      survival. However, the neural processes that prioritize conflicting survival
      needs are poorly understood. We discovered that hunger attenuates behavioral
      responses and affective properties of inflammatory pain without altering acute
      nociceptive responses. This effect is centrally controlled, as activity in hunger
      sensitive agouti-related protein (AgRP)-expressing neurons abrogates inflammatory
      pain. Systematic analysis of AgRP projection subpopulations revealed that the
      neural processing of hunger and inflammatory pain converge in the hindbrain
      parabrachial nucleus (PBN). Strikingly, activity in AgRP -> PBN neurons blocked
      the behavioral response to inflammatory pain as effectively as hunger or
      analgesics. The anti-nociceptive effect of hunger is mediated by neuropeptide Y
      (NPY) signaling in the PBN. By investigating the intersection between hunger and
      pain, we have identified a neural circuit that mediates competing survival needs
      and uncovered NPY Y1 receptor signaling in the PBN as a target for pain
      suppression.

PMID- 29570995
TI  - The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that
      Mediates Intercellular RNA Transfer.

PMID- 29570996
TI  - SnapShot: CGAS-STING Signaling.
AB  - CGAS responds to cytosolic DNA by initiating a STING-dependent response that
      ultimately engages innate immune effectors to ensure the preservation of
      organismal homeostasis.

PMID- 29570997
TI  - Gene Therapy for Retinal Degeneration.
AB  - Biallelic mutations in the RPE65 gene are associated with inherited retinal
      degenerations/dystrophies (IRD) and disrupt the visual cycle, leading to loss of
      vision. A new adenoviral vector-based gene therapy surgically delivered to
      retinal cells provides normal human RPE65 protein that can restore the visual
      cycle and some vision. To view this Bench to Bedside, open or download the PDF.

PMID- 29570998
TI  - The Predecessors Within . . .
AB  - By examining the genomes of present-day people from Asia, researchers show that
      modern humans met and interbred with Denisovans, distant relatives to
      Neanderthals, on at least two occasions. As a result, people today carry DNA from
      two different Denisovan populations.

PMID- 29571000
TI  - H2S to Mitigate Vascular Aging: A SIRT1 Connection.
AB  - H2S is an endogenous gasotransmitter that plays an important role in
      physiological conditions. In this issue, Das et al. provide evidence that SIRT1
      dependent angiogenesis is augmented by H2S-findings reinforced by Longchamp et
      al., who demonstrate that H2S-dependent angiogenesis is triggered by amino acid
      deprivation.

PMID- 29570999
TI  - Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of
      Vascular Aging.
AB  - A decline in capillary density and blood flow with age is a major cause of
      mortality and morbidity. Understanding why this occurs is key to future gains in
      human health. NAD precursors reverse aspects of aging, in part, by activating
      sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and
      dietary restriction (DR). We show that SIRT1 in endothelial cells is a key
      mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with
      the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and
      increases endurance in elderly mice by promoting SIRT1-dependent increases in
      capillary density, an effect augmented by exercise or increasing the levels of
      hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels.
      These findings have implications for improving blood flow to organs and tissues,
      increasing human performance, and reestablishing a virtuous cycle of mobility in
      the elderly.

PMID- 29570994
TI  - Metazoan MicroRNAs.
AB  - MicroRNAs (miRNAs) are ~22 nt RNAs that direct posttranscriptional repression of
      mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these
      small RNAs help sculpt the expression of most mRNAs. This article reviews
      advances in our understanding of the defining features of metazoan miRNAs and
      their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs
      are regulated, how they recognize and cause repression of their targets, and the
      biological functions of this repression, with a compilation of knockout
      phenotypes that shows that important biological functions have been identified
      for most of the broadly conserved miRNAs of mammals.

PMID- 29571001
TI  - Photobiomodulation reduces gliosis in the basal ganglia of aged mice.
AB  - This study explored the effects of long-term photobiomodulation (PBM) on the
      glial and neuronal organization in the striatum of aged mice. Mice aged 12 months
      were pretreated with PBM (670 nm) for 20 minutes per day, commencing at 5 months
      old and continued for 8 months. We had 2 control groups, young at 3 months and
      aged at 12 months old; these mice received no treatment. Brains were aldehyde
      fixed and processed for immunohistochemistry with various glial and neuronal
      markers. We found a clear reduction in glial cell number, both astrocytes and
      microglia, in the striatum after PBM in aged mice. By contrast, the number of 2
      types of striatal interneurons (parvalbumin+ and encephalopsin+), together with
      the density of striatal dopaminergic terminals (and their midbrain cell bodies),
      remained unchanged after such treatment. In summary, our results indicated that
      long-term PBM had beneficial effects on the aging striatum by reducing glial cell
      number; and furthermore, that this treatment did not have any deleterious effects
      on the neurons and terminations in this nucleus.

PMID- 29571002
TI  - Multiuser virtual worlds in healthcare education: A systematic review.
AB  - BACKGROUND: The use of multiuser virtual worlds (MUVWs) for collaborative
      learning has generated interest among healthcare educators. Published evidence to
      support its use is growing, but none has synthesized the evidence to guide future
      work. OBJECTIVE: This study sought to provide a comprehensive and systematic
      evaluation of MUVWs in healthcare education. DESIGN: A systematic review METHODS:
      A systematic search of five databases including CINAHL, Cochrane library, EMBASE,
      PubMed, and Scopus, was conducted from inception up to January 2017. Two
      independent researchers selected studies that met the inclusion criteria and
      assessed for methodological quality using the Medical Education Research Study
      Quality Instrument (MERSQI). A total of 18 studies were reviewed and their data
      were synthesized narratively using a 3-P model (presage-process-product).
      RESULTS: Average scores in the MERSQI for methodological quality are 10/18, which
      is modest. A rally by the government or professional bodies towards more
      collaborative working among healthcare professionals is a key driver behind
      implementing MUVWs. Funding is important for its development and evaluation. Team
      training in acute care and communication training were the most frequent learning
      objectives, and predominant learning activities include practice on simulation
      scenario and debriefing. Two-thirds of the studies did not explain their
      theoretical framework that underpinned their design and implementation of MUVWs.
      While MUVWs in healthcare education is generally well-received, learning outcomes
      remain inconclusive. CONCLUSION: Despite a growth of studies on the use of MUVW
      in healthcare education, there is a need for more understanding of the
      application of theories to inform the learning activities. Therefore, we suggest
      educators to incorporate a theoretical model to explain the learning processes
      behind MUVWs. To improve the quality of evidence, we call for researchers to
      employ a more rigorous and broader approach to evaluation that explicates longer
      term outcomes, including cost benefit analyses.

PMID- 29571003
TI  - Elucidating the substrate specificities of acyl-lipid thioesterases from diverse
      plant taxa.
AB  - Acyl-ACP thioesterase enzymes, which cleave fatty acyl thioester bonds to release
      free fatty acids, contribute to much of the fatty acid diversity in plants. In
      Arabidopsis thaliana, a family of four single hot-dog fold domain, plastid
      localized acyl-lipid thioesterases (AtALT1-4) generate medium-chain (C6-C14)
      fatty and beta-keto fatty acids as secondary metabolites. These volatile products
      may serve to attract insect pollinators or deter predatory insects. Homologs of
      AtALT1-4 are present in all plant taxa, but are nearly all uncharacterized.
      Despite high sequence identity, AtALT1-4 generate different lipid products,
      suggesting that ALT homologs in other plants also have highly varied activities.
      We investigated the catalytic diversity of ALT-like thioesterases by screening
      the substrate specificities of 15 ALT homologs from monocots, eudicots, a
      lycophyte, a green microalga, and the ancient gymnosperm Gingko biloba, via
      expression in Escherichia coli. Overall, these enzymes had highly varied
      substrate preferences compared to one another and to AtALT1-4, and could be
      classified into four catalytic groups comprising members from diverse taxa. Group
      1 ALTs primarily generated 14:1 beta-keto fatty acids, Group 2 ALTs produced 6-10
      carbon fatty/beta-keto fatty acids, Group 3 ALTs predominantly produced 12-14
      carbon fatty acids, and Group 4 ALTs mainly generated 16 carbon fatty acids.
      Enzymes in each group differed significantly in the quantities of lipids and
      types of minor products they generated in E. coli. Medium-chain fatty acids are
      used to manufacture insecticides, pharmaceuticals, and biofuels, and ALT-like
      proteins are ideal candidates for metabolic engineering to produce specific fatty
      acids in significant quantities.

PMID- 29571004
TI  - Signal transduction in artichoke [Cynara cardunculus L. subsp. scolymus (L.)
      Hayek] callus and cell suspension cultures under nutritional stress.
AB  - Stimulated production of secondary phenolic metabolites and proline was studied
      by using cell cultures of artichoke [Cynara cardunculus L. subsp. scolymus (L.)
      Hayek] submitted to nutritional stress. Artichoke cell cultures accumulated
      phenolic secondary metabolites in a pattern similar to that seen in artichoke
      leaves and heads (capitula). This paper shows that both callus and cell
      suspension cultures under nutritional stress accumulated phenolic compounds and
      proline, at the same time their biomass production was negatively affected by
      nutrient deficiency. The results obtained strongly suggest that plant tissues
      respond to nutrient deprivation by a defensive costly mechanism, which determines
      the establishment of a mechanism of trade-off between growth and adaptive
      response. Furthermore, the results of this research suggest that perception of
      abiotic stress and increased phenolic metabolites are linked by a sequence of
      biochemical processes that also involves the intracellular free proline and the
      oxidative pentose phosphate pathway. The main conclusion of this paper is that,
      once calli and cell suspension cultures respond to nutrient deficiency, in
      acclimated cells the establishment of a negative correlation between primary
      metabolism (growth) and secondary metabolism (defence compounds) is observed.

PMID- 29571005
TI  - Attentional control deficits in social anxiety: Investigating inhibition and
      shifting functions using a mixed antisaccade paradigm.
AB  - BACKGROUND AND OBJECTIVES: Attentional control has recently been assumed to play
      a critical role in the generation and maintenance of threat-related attentional
      bias and social anxiety. The present study aimed to investigate whether socially
      anxious (SA) individuals show impairments in attentional control functions,
      particularly in inhibition and shifting. METHODS: Forty-two SA and 41 non-anxious
      (NA) participants completed a mixed antisaccade task, a variant of the
      antisaccade task that is used to investigate inhibition as well as shifting
      functions. RESULTS: The results showed that, overall, SA participants had longer
      antisaccade latencies than NA participants, but the two groups did not differ in
      their antisaccade error rates. Moreover, in the single-task block, SA
      participants had longer latencies than NA participants for antisaccade but not
      prosaccade trials. In the mixed-task block, the SA participants had longer
      latencies than the NA participants for both task types. The two groups did not
      differ in their latency switch costs in the mixed-task blocks. LIMITATIONS:
      First, this study was conducted using a non-clinical sample of undergraduate
      students. Second, the antisaccade task measures primarily oculomotor inhibition.
      Third, this study did not include the measure of state anxiety to rule out the
      effects of state anxiety on the present findings. CONCLUSIONS: This study
      suggests that SA individuals demonstrate diminished efficiency of inhibition
      function but show no significant impairment of shifting function. However, in the
      mixed-task condition, SA individuals may exhibit an overall reduction in
      processing efficiency due to the higher task difficulty.

PMID- 29571006
TI  - Non-metric multidimensional scaling and human risks of heavy metal concentrations
      in wild marine organisms from the Maowei Sea, the Beibu Gulf, South China Sea.
AB  - We investigated heavy metal concentrations in wild marine organisms from Maowei
      Sea, a significant gulf of low-latitude developing regions of the Beibu Gulf,
      South China Sea. Twenty species, comprising fish, cephalopods, and crustaceans
      were collected and analyzed for heavy metals. Heavy metal levels (mg/kg, wet
      weight) in the aquatic organism samples were: 0.003-1.800 for Cd, 0.02-0.14 for
      Pb, 0.10-0.63 for Cr, 0.20-77.50 for Cu, 9.50-64.60 for Zn, 0.006-0.066 for Hg,
      and 0.10-1.50 for As. Non-metric multidimensional scaling coupled with cluster
      analysis revealed two groupings that mainly resulted from different species of
      the metals in marine organisms. The highest concentrations of Cd, Pb, Cr, Ni, Cu,
      Zn, Hg, and As were found in species of cephalopods. Health risk assessment based
      on the target hazard quotients (THQ) and total THQ indicated no significant
      adverse health effects from consumption of marine organisms.

PMID- 29571007
TI  - Time-restricted feeding influences immune responses without compromising muscle
      performance in older men.
AB  - OBJECTIVE: This study examined the effect of 12 wk of time-restricted feeding
      (TRF) on complete blood cell counts, natural killer cells, and muscle performance
      in 20- and 50-year-old men. METHODS: Forty active and healthy participants were
      randomly divided into young experimental, young control, aged experimental, and
      aged control group. Experimental groups participated in TRF. Before (P1) and
      after (P2) TRF, participants performed a maximal exercise test to quantify muscle
      power. Resting venous blood samples were collected for blood count calculation.
      RESULTS: No changes were identified in muscle power in all groups after TRF (P >
      0.05). At P1, red cells, hemoglobin, and hematocrit were significantly higher in
      young participants compared with elderly participants (P < 0.05). At P2, this age
      effect was not found in red cells between the young experimental group and the
      aged experimental group (P > 0.05). At P1, white blood cells and neutrophils were
      significantly higher in young participants compared with elderly participants (P
      < 0.05). At P2, only neutrophils decreased significantly (P < 0.05) in
      experimental groups without significant (P > 0.05) difference among them.
      Lymphocytes decreased significantly in the aged experimental group at P2 (P <
      0.05), whereas NKCD16+ and NKCD56+ decreased significantly in experimental groups
      at P2 (P < 0.05). TRF had no effect on CD3, CD4+, and CD8+ levels (P > 0.05).
      CONCLUSION: TRF decreases hematocrit, total white blood cells, lymphocytes, and
      neutrophils in young and older men. TRF may be effective in preventing
      inflammation by decreasing natural killer cells. As such, TRF could be a
      lifestyle strategy to reduce systemic low-grade inflammation and age-related
      chronic diseases linked to immunosenescence, without compromising physical
      performance.

PMID- 29571009
TI  - Lifelong calorie restriction affects indicators of colonic health in aging
      C57Bl/6J mice.
AB  - Diminished colonic health is associated with various age-related pathologies.
      Calorie restriction (CR) is an effective strategy to increase healthy lifespan,
      although underlying mechanisms are not fully elucidated. Here, we report the
      effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice.
      Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was
      associated with attenuated immune- and inflammation-related gene expression in
      the colon. Furthermore, expression of genes involved in lipid metabolism was
      higher upon CR, which may point towards efficient regulation of energy
      metabolism. The relative abundance of bacteria considered beneficial to colonic
      health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed
      to CR for 28 months as compared to the other diet groups. We found lower plasma
      levels of interleukin-6 and lower levels of various metabolites, among which are
      bile acids, in the colonic luminal content of CR-exposed mice as compared to the
      other diet groups. Switching from CR to an ad libitum moderate-fat diet at old
      age (24 months) revealed remarkable phenotypic plasticity in terms of gene
      expression, microbiota composition and metabolite levels, although expression of
      a subset of genes remained CR-associated. This study demonstrated in a
      comprehensive way that CR affects indicators of colonic health in aging mice. Our
      findings provide unique leads for further studies that need to address optimal
      and feasible strategies for prolonged energy deprivation, which may contribute to
      healthy aging.

PMID- 29571008
TI  - Grape proanthocyanidin-induced intestinal bloom of Akkermansia muciniphila is
      dependent on its baseline abundance and precedes activation of host genes related
      to metabolic health.
AB  - We previously showed that C57BL/6J mice fed high-fat diet (HFD) supplemented with
      1% grape polyphenols (GP) for 12 weeks developed a bloom of Akkermansia
      muciniphila with attenuated metabolic syndrome symptoms. Here we investigated
      early timing of GP-induced effects and the responsible class of grape
      polyphenols. Mice were fed HFD, low-fat diet (LFD) or formulations supplemented
      with GP (HFD-GP, LFD-GP) for 14 days. Mice fed HFD-GP, but not LFD-GP, showed
      improved oral glucose tolerance compared to controls. A. muciniphila bloom
      occurred earlier in mice fed LFD-GP than HFD-GP; however, timing was dependent on
      baseline A. muciniphila levels rather than dietary fat. Mice gavaged for 10 days
      with GP extract (GPE) or grape proanthocyanidins (PACs), each delivering 360 mg
      PACs/kg body weight, induced a bloom of fecal and cecal A. muciniphila, the rate
      of which depended on initial A. muciniphila abundance. Grape PACs were sufficient
      to induce a bloom of A. muciniphila independent of specific intestinal gene
      expression changes. Gut microbial community analysis and in vitro inhibition of
      A. muciniphila by GPE or PACs suggest that the A. muciniphila bloom in vivo
      occurs via indirect mechanisms.

PMID- 29571010
TI  - Fecal microbiome composition and stability in 4- to 8-year old children is
      associated with dietary patterns and nutrient intake.
AB  - How long-term dietary intake shapes microbiota composition and stability in young
      children is poorly understood. Herein, the temporal variability in stool
      microbiota composition in relation to habitual dietary patterns of 4- to 8-year
      old children (n=22) was investigated. Fecal samples were collected at baseline, 6
      weeks and 6 months. Bacterial composition and volatile fatty acids were assessed
      by 16S rRNA sequencing and gas-chromatography, respectively. Nutrient intake was
      assessed using 3-day food diaries and dietary patterns were empirically derived
      from a food frequency questionnaire. Using a factor loading of >0.45 for a food
      group to be a major contributor to the overall dietary pattern, two dietary
      patterns were found to be associated with distinct microbiome composition.
      Dietary Pattern 1 (DP1), characterized by intake of fish, protein foods, refined
      carbohydrates, vegetables, fruit, juice and sweetened beverages, kid's meals and
      snacks and sweets, was associated with higher relative abundance of
      Bacteroidetes, Bacteroides and Ruminococcus and lower abundance of
      Bifidobacterium, Prevotella, Blautia and Roseburia. Dietary Pattern 2 (DP2),
      characterized by intake of grains, dairy and legumes, nuts and seeds, was
      associated with higher relative abundance of Cyanobacteria and
      Phascolarctobacterium and lower abundance of Dorea and Eubacterium. Fruit and
      starchy foods were present in both patterns, but were more associated with DP1
      and DP2, respectively. Temporal stability of microbiota over a 6-month period was
      associated with baseline dietary patterns. Understanding how dietary intake
      contributes to microbiota composition and stability in early life in important
      for dietary recommendations and designing clinical interventions for microbiota
      associated diseases.

PMID- 29571011
TI  - Factors influencing noncompliance with bicycle passing distance laws.
AB  - Many jurisdictions around the world have implemented laws to require a minimum
      distance when motor vehicles pass cyclists, but research into the factors
      influencing passing distances has produced inconsistent results, indicating the
      need for future research. This study examined the factors influencing motorists'
      compliance with a legislated bicycle passing distance rule in Queensland,
      Australia. Unlike the earlier studies, which used volunteer riders to record
      passing events, this study used a naturalistic study design to record passing
      events where none of the motorists or the cyclists were aware of being studied.
      As a result, this study captured the 'true' driving and riding behaviours during
      passing events. The likelihood of non-compliance was greater on higher (70-80
      km/h speed limits) and lower (40 km/h) speed roads than 60 km/h roads, at curved
      road sections, and on roads with narrower traffic lanes. Rider characteristics
      (age, gender, helmet status, type of clothing, type of bicycle, and individual or
      group riding) had no statistically significant association with compliance
      status. The findings indicate that efforts to improve cyclist safety during
      overtaking events should focus on non-rider related factors, such as roadway
      infrastructure characteristics.

PMID- 29571012
TI  - Have pedestrian subsystem tests improved passenger car front shape?
AB  - Subsystem impactor tests are the main approaches for evaluation of safety
      performance of vehicle front design for pedestrian protection in legislative
      regulations. However, the main aspects of vehicle safety for pedestrians are
      shape and stiffness, and though it is clear that subsystem impact tests encourage
      lower vehicle front stiffness, it is unclear whether they promote improved
      vehicle front shapes for pedestrian protection. The purpose of this paper is
      therefore to investigate the effects of European pedestrian safety regulations on
      passenger car front shape and pedestrian injury risk using recent German In-Depth
      Accident Study (GIDAS) pedestrian collision data and numerical simulations.
      Firstly, a sample of 579 pedestrian collision cases involving 190 different car
      models between 2000-2015 extracted from the GIDAS was used to compare front-end
      shapes of passenger cars manufactured before and after the legislative pedestrian
      safety regulations were introduced in Europe. The focus was on changes in
      passenger car front shape and differences in pedestrian AIS2+ (Abbreviated Injury
      Scale at least level 2) leg, pelvis/femur and head injury risk observed in
      collisions. Multi-body simulations were also used to assess changes in vehicle
      aggressivity due to the observed changes in vehicle shape. The results show that
      newer passenger cars tend to have a flatter and wider bumper, higher bonnet
      leading edge, shorter and steeper bonnet and a shallower windscreen. Both the
      collision data and the numerical simulations indicate that newer passenger car
      front bumper designs are significantly safer for pedestrians' legs. However, the
      results also show that the higher bonnet leading edge in newer passenger cars is
      poor for pedestrian pelvis/femur protection, even though newer cars show an
      obviously lower AIS2+ injury risk to younger pedestrians in collisions. Newer
      cars have a lower AIS2+ head injury risk for pedestrians in collisions, but the
      numerical analysis indicate that this is not likely due to shape changes in
      passenger car fronts. Overall, the introduction of pedestrian safety regulations
      has resulted in reductions in pedestrian injury risk, but further benefits would
      accrue from tests which promote a lower bonnet leading edge. The influence of
      vehicle shape on pedestrian head injury risk remains unclear.

PMID- 29571013
TI  - A ternary complex model of Sirtuin4-NAD+-Glutamate dehydrogenase.
AB  - Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information
      regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit
      flies and mice. Sirt4 is localized in the mitochondria, where it contributes to
      preventing the development of cancers and ischemic heart disease through
      regulating energy metabolism. The ADP-ribosylation of glutamate dehydrogenase
      (GDH), which is catalyzed by Sirt4, downregulates the TCA cycle. However, this
      reaction mechanism is obscure, because the structure of Sirt4 is unknown. We here
      constructed structural models of Sirt4 by homology modeling and threading, and
      docked nicotinamide adenine dinucleotide+ (NAD+) to Sirt4. In addition, a partial
      GDH structure was docked to the Sirt4-NAD+ complex model. In the ternary complex
      model of Sirt4-NAD+-GDH, the acetylated lysine 171 of GDH is located close to
      NAD+. This suggests a possible mechanism underlying the ADP-ribosylation at
      cysteine 172, which may occur through a transient intermediate with ADP
      ribosylation at the acetylated lysine 171. These results may be useful in
      designing drugs for the treatment of cancers and ischemic heart disease.

PMID- 29571014
TI  - Sanguinarine inhibits epithelial ovarian cancer development via regulating long
      non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-kappaB signaling or
      PI3K/AKT/mTOR pathway.
AB  - OBJECTIVE: This study aimed to investigate the antitumor effects and possible
      regulatory mechanisms of sanguinarine in epithelial ovarian cancer. MATERIAL AND
      METHODS: The effects of sanguinarine on the malignant behaviors of epithelial
      ovarian cancer SKOV3 cells and the expression of long non-coding RNA CASC2 were
      investigated. The expression of CASC2 and EIF4A3 in epithelial ovarian cancer
      tissues and cells were detected, and the potential mechanisms of sanguinarine
      were explored by investigating the interactions between CASC2 and EIF4A3.
      Furthermore, the regulatory relationship between sanguinarine and nuclear factor
      kappaB (NF-kappaB) signaling or PI3K/AKT/mTOR pathway was explored. RESULTS:
      Sanguinarine exhibited antitumor effects in SKOV3 cells by significantly
      inhibiting cell viability, migration and invasion and promoting cell apoptosis.
      Moreover, sanguinarine induced CASC2 expression and silencing of CASC2 reversed
      the effects of sanguinarine in epithelial ovarian cancer cells. CASC2 was
      significantly lowly expressed in ovarian cancer tissues and cells, while EIF4A3
      was highly expressed. EIF4A3 was identified as a CASC2 binding protein. Knockdown
      of EIF4A3 reversed the effects of sanguinarine plus CASC2 silencing. Besides,
      sanguinarine markedly inhibited the activation of NF-kappaB signaling or
      PI3K/AKT/mTOR pathway, which was reversed by CASC2 silencing. And the effects of
      sanguinarine plus CASC2 silencing on the activation of these pathways were
      further reversed after knockdown of EIF4A3 at the same time. CONCLUSIONS: Our
      findings reveal that sanguinarine exhibits antitumor effects in epithelial
      ovarian cancer cells possible via regulating CASC2-EIF4A3 axis and/or inhibiting
      NF-kappaB signaling or PI3K/AKT/mTOR pathway. Sanguinarine may serve as a
      potential therapeutic reagent for epithelial ovarian cancer.

PMID- 29571015
TI  - Enhanced lipoxygenase/LTD4 signaling accounts for the exaggerated hypertensive
      and nephrotoxic effects of cyclosporine plus indomethacin in rats.
AB  - The combined use of cyclosporine (CSA) and nonsteroidal antiinflammatory drugs
      (NSAIDs) causes exaggerated rises in systolic blood pressure (SBP) and
      nephrotoxicity. We examined whether these influences relate to the arachidonate/5
      lipoxygenase (LOX) pathway. Rats were treated with CSA (20 mg kg-1 day-1),
      indomethacin (5 mg kg-1 day-1), or their combination for 10 days. Changes in SBP
      and renal biochemical/histopathological characteristics along with leukotriene
      levels were determined in rats treated with or without LT receptor antagonists.
      CSA or indomethacin caused: (i) renal tubular atrophy and interstitial fibrosis,
      (ii) increases in serum creatinine, blood urea nitrogen (BUN), and renal LTD4,
      LTB4, TNF-alpha, TGF-beta1, and caspase-3, and (iii) decreases in renal PGE2 and
      total antioxidant capacity (TAC). SBP measured by tail-cuff plethysmography was
      increased by CSA but not indomethacin. These effects were mostly intensified in
      rats treated with CSA plus indomethacin. The co-treatment with montelukast
      (cysteinyl LT receptor blocker), but not ONO-4057 (LTB4 receptor blocker),
      ameliorated CSA/indomethacin-evoked hypertension, renal structural/biochemical
      deterioration, and LTD4 levels. Moreover, montelukast exhibited a greater
      capacity in reversing inflammatory, oxidative, apoptotic, and fibrotic
      abnormalities induced by CSA/indomethacin. Overall, lipoxygenase/LTD4
      upregulation contributes to the exaggerated hypertension and nephrotoxicity
      caused by CSA/indomethacin. The therapeutic potential of cysteinyl LT receptor
      antagonism in rectifying CSA/NSAIDs-evoked anomalies is warranted.

PMID- 29571016
TI  - The role of nutrients in the pathogenesis and treatment of migraine headaches:
      Review.
AB  - OBJECTIVE: Migraine as a disabling neurovascular disease affects 6% of men and
      18% of women worldwide. The deficiency of many nutrients including magnesium,
      niacin, riboflavin, cobalamin, coenzymes Q10, carnitine, alpha-lipoic acid and
      vitamin D is associated with migraine. Some researchers postulate that
      mitochondrial dysfunction and impaired antioxidant status can cause migraine.
      Also increase in homocysteine level can lead to migraine attacks; therefore, some
      Nutraceuticals play a vital role in migraine prevention. Thus, the aim of the
      current study was to review randomized controlled trials (RCT) assessing the
      effect of nutritional supplements on migraine patients. METHODS: English articles
      in the following databases were searched: MEDLINE, AMED, EMBASE and Cochrane
      Library. In this manuscript, RCTs published during 1990-2017 were reviewed.
      RESULTS: Evidences indicate that supplementation with magnesium, carnitine,
      riboflavin, niacin, CoQ10, vitamin D, Vitamin B12 and alpha lipoic acid have
      prophylactic and therapeutic effects on migraine patients. CONCLUSION: Due to the
      possible side effects of pharmacological drugs and drug addictions, the use of
      nutrient compounds alone or in combination with routine cures have been proposed.
      However, further constructive studies are required.

PMID- 29571017
TI  - Long noncoding RNA SNHG7 accelerates prostate cancer proliferation and cycle
      progression through cyclin D1 by sponging miR-503.
AB  - Increasing evidence has indicated the important roles of long non-coding RNAs
      (lncRNAs) in tumorigenesis and cellular progression, including prostate cancer.
      In this study, we aim to investigate the expression level of SNHG7 and its
      biological functions on prostate cancer cells. Results indicated that SNHG7
      expression was significantly up-regulated in prostate cancer tissue and cell
      lines. Besides, the overexpression of SNHG7 was closely correlated with the poor
      prognosis. In vitro and in vivo, experiments demonstrated that SNHG7 knockdown
      markedly inhibited prostate cancer proliferation and cycle-related protein (CDK4,
      CDK6, Cyclin D1), induced cell cycle arrest at G0/G1 phase and suppressed tumor
      growth. Moreover, miR-503 was predicted by bioinformatics tools and validated
      using luciferase reporter assay to both directly inhibited SNHG7 and Cyclin D1
      expression by targeting their RNA 3'-UTR. In conclusion, results present that
      SNHG7 regulates the cycle progression and acts as an oncogenic gene in the
      prostate cancer tumorigenesis via miR-503/Cyclin D1 pathway, revealing the vital
      role of lncRNA/miRNA/mRNA axis in prostate cancer carcinogenesis.

PMID- 29571018
TI  - Stem cell therapy in Asherman syndrome and thin endometrium: Stem cell- based
      therapy.
AB  - The endometrium is one of the essential components of the uterus. The endometrium
      of human is a complex and dynamic tissue, which undergoes periods of growth and
      turn over during any menstrual cycle. Stem cells are initially undifferentiated
      cells that display a wide range of differentiation potential with no distinct
      morphological features. Stem cell therapy method recently has become a novel
      procedure for treatment of tissue injury and fibrosis in response to damage.
      Currently, there is massive interest in stem cells as a novel treatment method
      for regenerative medicine and more specifically for the regeneration of human
      endometrium disorder like Asherman syndrome (AS) and thin endometrium. AS also
      known as intrauterine adhesion (IUA) is a uterine disorder with the aberrant
      creation of adhesions within the uterus and/or cervix. Patients with IUA are
      significantly associated with menstrual abnormalities and suffer from pelvic
      pain. In addition, IUA might prevent implantation of the blastocyst, impair the
      blood supply to the uterus and early fetus, and finally result in the recurrent
      miscarriage or infertility in the AS patients. It has been evidenced that the
      transplantation of different stem cells with a diverse source in the endometrial
      zone had effects on endometrium such as declined the fibrotic area, an elevated
      number of glands, stimulated angiogenesis, the enhanced thickness of the
      endometrium, better formed tissue construction, protected gestation, and improved
      pregnancy rate. This study presents a summary of the investigations that indicate
      the key role of stem cell therapy in regeneration and renovation of defective
      parts.

PMID- 29571019
TI  - Involvement of estrogen receptors in silibinin protection of pancreatic beta
      cells from TNFalpha- or IL-1beta-induced cytotoxicity.
AB  - Silibinin is a polyphenolic flavonoid that exhibits anticarcinogenic, anti
      inflammatory and cytoprotective effects. The effect of silibinin on pancreatic
      islet beta-cell is yet largely unknown in spite of well documented
      hepatoprotective effects. Protecting the functional insulin-producing beta-cells
      in the pancreas is a major therapeutic challenge in the patients with type 1
      (T1DM) or type 2 diabetes mellitus (T2DM). This study reports the effect of
      silibinin on the rat pancreatic beta-cell line, INS-1, damaged with pro
      inflammatory cytokine, TNFalpha or IL-1beta. Exposure to TNFalpha or IL-1beta for
      48 h caused INS-1 cells to reduce the production of insulin as well as cell
      viability. These actions of TNFalpha or IL-1beta are associated with suppression
      of the expression of estrogen receptors (ERs). Further study revealed that
      silibinin protected the suppression in the expression of both ERalpha and ERbeta
      that were involved in insulin synthesis and release, respectively. Furthermore,
      evidence is obtained that silibinin may impede the loss of critical INS-1 cells
      by promoting autophagy and preventing apoptosis. Direct cytoprotective effects of
      silibinin on INS-1 cells suggest that silibinin may be therapeutically beneficial
      for diabetes.

PMID- 29571021
TI  - Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by
      interference of the sympathetic inhibitory pathway in hypertensive rat.
AB  - Olmesartan-associated enteropathy (OAE) is a life-threatening pathological
      condition, but its underlying mechanisms have not been elucidated. Although
      intestinal hypermotility is frequently accompanied by chronic diarrhea, there
      have been no studies of olmesartan-induced hypermotility. Intestinal motility
      should be well regulated by the enteric nervous system, but degeneration of
      enteric neurons has been reported in patients with chronic diarrheal diseases,
      such as irritable bowel syndrome, suggesting a connection between OAE and
      intestinal hypermotility. In this study, interference with this inhibitory
      pathway was analyzed in a model of olmesartan-induced intestinal hypermotility
      (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing
      stress. The effects of the potent inhibitory neurotransmitters norepinephrine
      (NE) and sodium nitroprusside (SNP), which act via different pathways, were
      assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous
      contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent
      in OAE, including atrophy of the intestinal epithelium and weight loss, were
      observed in these rats. Interestingly, olmesartan significantly elevated heart
      rate while lowering blood pressure in OIH rats. These abnormal conditions were
      prevented by adding linalyl acetate (LA), while the blood pressure-lowering
      effects of olmesartan were maintained. These findings suggest that olmesartan
      induces intestinal hypermotility by interfering with the sympathetic inhibitory
      pathway, and reduces epithelial cell size or body weight in hypertensive rats. As
      LA prevented these effects, combination treatment with olmesartan plus LA may
      provide better antihypertensive efficacy without inducing OAE.

PMID- 29571020
TI  - Experimental diabetes induced by streptozotocin in the desert gerbil, Gerbillus
      gerbillus, and the effects of short-term 20-hydroxyecdysone administration.
AB  - The present work was aimed at studying the effects of streptozotocin (STZ; 130
      mg/kg) in the desert gerbil, Gerbillus gerbillus, and at evaluating the impact of
      the short-term administration of 20-hydroxyecdysone (20E; 5 mg/kg). We observed
      that administration of streptozotocin caused a significant increase in plasmatic
      glucose and a decrease in insulin levels. The plasma lipid profile and liver
      glycogen content were also altered. The activities of antioxidant enzymes and
      malondialdehyde (MDA) levels were increased in the pancreatic tissue of STZ
      treated gerbils. Moreover, histopathological and immunohistochemical analysis
      showed degenerative damage in the pancreas with a decline in the percentage area
      of beta-cells. Treatment of STZ-treated gerbils with 20E counteracted metabolic
      disorders and reduced lipid peroxidation. Histological and immunohistochemical
      studies showed moderate amelioration in the pancreatic structure. These findings
      indicate that streptozotocin administration induced experimental diabetes in
      gerbils and that short-term administration of 20E has beneficial effects in
      glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate
      surviving beta-cells to release more insulin.

PMID- 29571022
TI  - TNF-alpha contributes to postmenopausal osteoporosis by synergistically promoting
      RANKL-induced osteoclast formation.
AB  - Previous studies showed that inflammatory cytokines promote osteoclast formation,
      characterized by the function of bone resorption. However, it remains unclear
      whether inflammatory factors contribute to osteoporosis syndrome in
      postmenopausal women. Here, we found that postmenopausal women with osteoporosis
      (PO) had increased levels of TNF-alpha, compared with those without osteoporosis.
      TNF-alpha is highly correlated with the RANK and estrogen levels in PO patients.
      in vitro, TNF-alpha synergistically promotes RANKL-induced osteoclast formation
      by activation of NF-kappaB and PI3K/Akt signaling. Moreover, inhibition of
      PI3K/Akt totally blocked the synergistic effects of TNF-alpha on NF-kappaB
      activation as well as osteoclast formation. Together, these results demonstrate
      that TNF-alpha synergistically promotes RANKL-induced osteoclasts formation
      through activation of PI3K/Akt signaling, which ultimately contributes to
      osteoporosis syndrome in postmenopausal women.

PMID- 29571023
TI  - Pretreatment with taurine prevented brain injury and exploratory behaviour
      associated with administration of anticancer drug cisplatin in rats.
AB  - The neurotoxicity associated with cisplatin treatment is one of the major side
      effects compromising the efficacy of the anti-cancer treatment. The present study
      investigated the possible protective effects of taurine, an intracellular amino
      acid, on cisplatin-induced brain injury and exploratory behaviour using five
      groups of ten female rats each. Group I received drinking water only. Group II
      orally received taurine alone at 200 mg/kg whereas Group III received cisplatin
      alone intraperitoneally at 10 mg/kg. Groups IV and V were treated with taurine at
      100 and 200 mg/kg respectively for sixteen consecutive days and a single
      intraperitoneal injection of cisplatin on day 13 to induce neurotoxicity.
      Endpoint analyses using video-tracking software revealed that cisplatin
      administration alone caused neurobehavioral deficits evinced by marked decrease
      in the total distance travelled, average speed, total time mobile, total mobile
      episode, number of crossing and absolute turn angle. Furthermore, cisplatin alone
      significantly suppressed brain antioxidant defense mechanisms, elevated nitric
      oxide and lipid peroxidation levels whereas it increased acetylcholinesterase
      activity in the treated rats. However, rats pretreated with taurine exhibited
      significant improvement in behavioural performance and brain antioxidant status
      with concomitant decrease in acetylcholinesterase activity and oxidative stress
      indices when compared with cisplatin alone group. Histologically, taurine
      pretreatment prevented cisplatin-induced neuronal death in the cerebral and
      cerebellar cortices, caudo-putamen and hippocampus as well as abrogated cisplatin
      mediated decrease in the dendritic arborization and mean diameter of the somata
      of pyramidal neurons in the treated rats. In conclusion, taurine may be a
      possible protective supplement to reduce cisplatin-induced side-effects including
      neurotoxicity in patients undergoing cisplatin treatment.

PMID- 29571024
TI  - OzPythonPlex: An optimised forensic STR multiplex assay set for the Australasian
      carpet python (Morelia spilota).
AB  - Reptile species, and in particular snakes, are protected by national and
      international agreements yet are commonly handled illegally. To aid in the
      enforcement of such legislation, we report on the development of three 11-plex
      assays from the genome of the carpet python to type 24 loci of tetra-nucleotide
      and penta-nucleotide repeat motifs (pure, compound and complex included). The
      loci range in size between 70 and 550 bp. Seventeen of the loci are newly
      characterised with the inclusion of seven previously developed loci to facilitate
      cross-comparison with previous carpet python genotyping studies. Assays were
      optimised in accordance with human forensic profiling kits using one nanogram
      template DNA. Three loci are included in all three of the multiplex reactions as
      quality assurance markers, to ensure sample identity and genotyping accuracy is
      maintained across the three profiling assays. Allelic ladders have been developed
      for the three assays to ensure consistent and precise allele designation. A DNA
      reference database of allele frequencies is presented based on 249 samples
      collected from throughout the species native range. A small number of validation
      tests are conducted to demonstrate the utility of these multiplex assays. We
      suggest further appropriate validation tests that should be conducted prior to
      the application of the multiplex assays in criminal investigations involving
      carpet pythons.

PMID- 29571025
TI  - Assessing cadmium exposure risks of vegetables with plant uptake factor and soil
      property.
AB  - Plant uptake factors (PUFs) are of great importance in human cadmium (Cd)
      exposure risk assessment while it has been often treated in a generic way. We
      collected 1077 pairs of vegetable-soil samples from production fields to
      characterize Cd PUFs and demonstrated their utility in assessing Cd exposure
      risks to consumers of locally grown vegetables. The Cd PUFs varied with plant
      species and pH and organic matter content of soils. Once normalized PUFs against
      soil parameters, the PUFs distributions were log-normal in nature. In this
      manner, the PUFs were represented by definable probability distributions instead
      of a deterministic figure. The Cd exposure risks were then assessed using the
      normalized PUF based on the Monte Carlo simulation algorithm. Factors affecting
      the extent of Cd exposures were isolated through sensitivity analyses. Normalized
      PUF would illustrate the outcomes for uncontaminated and slightly contaminated
      soils. Among the vegetables, lettuce was potentially hazardous for residents due
      to its high Cd accumulation but low Zn concentration. To protect 95% of the
      lettuce production from causing excessive Cd exposure risks, pH of soils needed
      to be 5.9 and above.

PMID- 29571026
TI  - Green synthesis of tannin-hexamethylendiamine based adsorbents for efficient
      removal of Cr(VI).
AB  - Newly developed adsorbents, poly(tannin-hexamethylendiamine) (PTHA), were
      fabricated by varying the mole ratio of tannin (TA) and hexamethylendiamine (HA)
      under one-pot reaction. The specific forming process of the adsorbent which had
      undergone the transition from hydrogen bonds to covalent bonds was subsequently
      explored. Based on the efficiency of Cr(VI) removal from aqueous solution over
      all prepared adsorbents, the PTHA-4 (mole ratio of TA/HA = 1:12.5) exhibited an
      excellent adsorption behavior. Adsorption experiments affected by contact time
      and ionic strength have been conducted successively by PTHA-4, and the
      equilibrium was reached at 24 h. The kinetic data revealed that the adsorption
      was good agreement with pseudo-second order model and needed to undergo the rate
      controlling step. The maximum adsorption capacity was 283.29 mg/g at 30  degrees
      C, relying on the isothermal curve suitably described by Langmuir model.
      Furthermore, toxic Cr(VI) had been reduced to the low toxic Cr(III) during
      adsorption process. The structures and adsorption performance of adsorbent were
      confirmed by means of SEM, FT-IR, XPS etc. Thus, the cheap-sustainable adsorbents
      have a superior feature for Cr(VI)-wastewater purification in future.

PMID- 29571027
TI  - Construction of multifunctional MoSe2 hybrid towards the simultaneous
      improvements in fire safety and mechanical property of polymer.
AB  - Organic modification of MoSe2 sheets is firstly achieved by Atherton-Todd
      reaction, aiming at the acquisition of multifunctional MoSe2 hybrid. Simultaneous
      enhancements in fire safety and mechanical property of thermalplastic
      polyurethane (TPU) are obtained with the presence of this hybrid. Strong
      interfacial interactions between the functionalized MoSe2 sheets and TPU can be
      obtained, making more efficient load transfer from the weak polymer chains to the
      robust sheets. Besides, more coherent barrier network may be formed in polymer
      matrix, restraining the diffusion of decomposed fragments and reducing the supply
      for combustion fuel. Consequently, the decreases in heat release are observed for
      polymer composites. Notably, the releases of toxic gases, such as HCN and CO, are
      also suppressed by this barrier network, resulting in the reductions in fire
      toxicity. This work may open a new door for the functionalization of MoSe2 sheets
      and evoke significant developments in its promising applications.

PMID- 29571028
TI  - Automatic imitation effects are influenced by experience of synchronous action in
      children.
AB  - By their fourth year of life, children are expert imitators, but it is unclear
      how this ability develops. One approach suggests that certain types of experience
      might forge associations between the sensory and motor representations of an
      action that may facilitate imitation at a later time. Sensorimotor experience of
      this sort may occur when an infant's action is imitated by a caregiver or when
      socially synchronous action occurs. This learning approach, therefore, predicts
      that the strength of sensory-motor associations should depend on the frequency
      and quality of previous experience. Here, we tested this prediction by examining
      automatic imitation, that is, the tendency of an action stimulus to facilitate
      the performance of that action and interfere with the performance of an
      incompatible action. We required children (aged between 3 years 8 months and 7
      years 11 months) to respond to actions performed by an experimenter (e.g., two
      hands clapping) with both compatible actions (i.e., two hands clapping) and
      incompatible actions (i.e., two hands waving) at different stages in the
      experimental procedure. As predicted by a learning account, actions thought to be
      performed in synchrony (i.e., clapping/waving) produced stronger automatic
      imitation effects when compared with actions where previous sensorimotor
      experience is likely to be more limited (e.g., pointing/hand closing).
      Furthermore, these automatic imitation effects were not found to vary with age,
      with both compatible and incompatible responses quickening with age. These
      findings suggest a role for sensorimotor experience in the development of
      imitative ability.

PMID- 29571029
TI  - CD137: A checkpoint regulator involved in atherosclerosis.
AB  - Inflammation is associated with atherosclerotic plaque development and
      precipitation of myocardial infarction and stroke, and anti-inflammatory therapy
      may reduce disease severity. Costimulatory molecules are key regulators of immune
      cell activity and inflammation, and are associated with disease development in
      atherosclerosis. Accumulating evidence indicates that a costimulatory molecule of
      the Tumor Necrosis Factor Receptor superfamily, the checkpoint regulator CD137,
      promotes atherosclerosis and vascular inflammation in experimental models. In
      light of the burgeoning consideration of CD137-targeted therapy in the clinic, it
      will be important to better understand costimulator immunobiology in development
      of cardiovascular disease. Here, we review available data on the costimulator
      CD137 and its potential role in atherosclerosis.

PMID- 29571030
TI  - Prediction of new-onset atrial fibrillation after first-ever ischemic stroke: A
      comparison of CHADS2, CHA2DS2-VASc and HATCH scores and the added value of stroke
      severity.
AB  - BACKGROUND AND AIMS: Early detection of atrial fibrillation after stroke is
      important for secondary prevention in stroke patients without known atrial
      fibrillation (AF). We aimed to compare the performance of CHADS2, CHA2DS2-VASc
      and HATCH scores in predicting AF detected after stroke (AFDAS) and to test
      whether adding stroke severity to the risk scores improves predictive
      performance. METHODS: Adult patients with first ischemic stroke event but without
      a prior history of AF were retrieved from a nationwide population-based database.
      We compared C-statistics of CHADS2, CHA2DS2-VASc and HATCH scores for predicting
      the occurrence of AFDAS during stroke admission (cohort I) and during follow-up
      after hospital discharge (cohort II). The added value of stroke severity to
      prediction models was evaluated using C-statistics, net reclassification
      improvement, and integrated discrimination improvement. RESULTS: Cohort I
      comprised 13,878 patients and cohort II comprised 12,567 patients. Among them,
      806 (5.8%) and 657 (5.2%) were diagnosed with AF, respectively. The CHADS2 score
      had the lowest C-statistics (0.558 in cohort I and 0.597 in cohort II), whereas
      the CHA2DS2-VASc score had comparable C-statistics (0.603 and 0.644) to the HATCH
      score (0.612 and 0.653) in predicting AFDAS. Adding stroke severity to each of
      the three risk scores significantly increased the model performance. CONCLUSIONS:
      In stroke patients without known AF, all three risk scores predicted AFDAS during
      admission and follow-up, but with suboptimal discrimination. Adding stroke
      severity improved their predictive abilities. These risk scores, when combined
      with stroke severity, may help prioritize patients for continuous cardiac
      monitoring in daily practice.

PMID- 29571031
TI  - Defining the upper extremity range of motion for safe automobile driving.
AB  - BACKGROUND: There are no guidelines for return to driving following upper
      extremity injury. A greater comprehension of the role of the upper extremity in
      driving is required to assist clinicians in their fitness-to-drive assessments.
      This research aims to assist clinicians by analyzing the motion at the upper
      extremity in safe automobile driving. METHODS: Thirty-six participants were
      recruited to the Monash University Accident Research Centre's driving simulator.
      They were tested in a realistic driving simulation using highway scenarios and
      traffic hazards. An OptiTrackTM motion tracking system recorded participants'
      upper limb movements. FINDINGS: The following ranges of motion were recorded
      (left and right arm mean whole numbers): The shoulder flexed from 14 to 54
      degrees , abducted to 18 degrees and adducted to 9 degrees . Shoulder rotation
      ranged from 6 degrees  external to 32 degrees  internal rotation. Elbow flexion
      ranged from 35 degrees  to 72 degrees . Pronation reached 77 degrees  and
      supination to 24 degrees . Wrist flexion reached 34 degrees  and extension
      reached 23 degrees . The wrist deviated to 17 degrees radially and 38 degrees 
      ulnar. To avoid simulated hazards, the steering wheel revolved 57.2 degrees  (SD
      19.2). The key movements in hazard avoidance are shoulder flexion, shoulder
      rotation, forearm rotation and wrist deviation. INTERPRETATION: Shoulder flexion,
      internal rotation and forearm rotation have been shown to be key upper extremity
      movements in safe driving. Clinicians can refer to the ranges of motion recorded
      in this investigation, or the driving task at hand in their fitness-to-drive
      assessments. The ability to revolve the steering wheel 100 degrees  exceeds the
      95th percentile of the steering wheel revolution angle required to avoid
      simulated traffic hazards.

PMID- 29571032
TI  - Computer-assisted design and finite element simulation of braces for the
      treatment of adolescent idiopathic scoliosis using a coronal plane radiograph and
      surface topography.
AB  - BACKGROUND: Orthopedic braces made by Computer-Aided Design and Manufacturing and
      numerical simulation were shown to improve spinal deformities correction in
      adolescent idiopathic scoliosis while using less material. Simulations with
      BraceSim (Rodin4D, Groupe Lagarrigue, Bordeaux, France) require a sagittal
      radiograph, not always available. The objective was to develop an innovative
      modeling method based on a single coronal radiograph and surface topography, and
      assess the effectiveness of braces designed with this approach. METHODS: With a
      patient coronal radiograph and a surface topography, the developed method allowed
      the 3D reconstruction of the spine, rib cage and pelvis using geometric models
      from a database and a free form deformation technique. The resulting 3D
      reconstruction converted into a finite element model was used to design and
      simulate the correction of a brace. The developed method was tested with data
      from ten scoliosis cases. The simulated correction was compared to analogous
      simulations performed with a 3D reconstruction built using two radiographs and
      surface topography (validated gold standard reference). FINDINGS: There was an
      average difference of 1.4 degrees /1.7 degrees  for the thoracic/lumbar Cobb
      angle, and 2.6 degrees /5.5 degrees  for the kyphosis/lordosis between the
      developed reconstruction method and the reference. The average difference of the
      simulated correction was 2.8 degrees /2.4 degrees  for the thoracic/lumbar Cobb
      angles and 3.5 degrees /5.4 degrees  the kyphosis/lordosis. INTERPRETATION: This
      study showed the feasibility to design and simulate brace corrections based on a
      new modeling method with a single coronal radiograph and surface topography. This
      innovative method could be used to improve brace designs, at a lesser radiation
      dose for the patient.

PMID- 29571033
TI  - Child maltreatment and adult depressive symptoms: Roles of self-compassion and
      gratitude.
AB  - Child maltreatment, including abuse (physical, emotional, and sexual) and neglect
      (physical and emotional), is positively associated with depressive symptoms in
      adulthood. However, most studies have been conducted within a psychopathological
      framework and focused on underlying dysfunctional processes (e.g., insecure
      attachment styles, maladaptive schemas, and negative attribution styles).
      Protective factors that affect the relationship between child maltreatment and
      adult depressive symptoms are underexplored. Guided by emotion regulation theory
      and the perspective of positive psychology, we examined the roles of self
      compassion and gratitude as protective factors in the relationship between child
      maltreatment and adult depressive symptoms in a sample of 358 college students.
      Results showed that psychological maltreatment (emotional abuse and emotional
      neglect) was associated with adult depressive symptoms through decreased self
      compassion. Neglect (emotional neglect and physical neglect) and sexual abuse
      were associated with adult depressive symptoms through decreased gratitude. There
      was no association between physical abuse and depressive symptoms through either
      self-compassion or gratitude. Our findings suggest that clinical practices
      focusing on self-compassion and gratitude might help prevent the development of
      adult depressive symptoms among clients with a history of maltreatment in
      childhood.

PMID- 29571034
TI  - Recommendations and requirements for reporting on applications of electric pulse
      delivery for electroporation of biological samples.
AB  - Electric field-induced membrane changes are an important approach in the life
      sciences. However, the developments in knowledge and translational applications
      face problems of reproducibility. Indeed, a quick survey of the literature
      reveals a lack of transparent and comprehensive reporting of essential technical
      information in many papers. Too many of the published scientific papers do not
      contain sufficient information for proper assessment of the presented results.
      The general rule/guidance in reporting experimental data should require details
      on exposure conditions such that other researchers are able to evaluate, judge
      and reproduce the experiments and data obtained. To enhance dissemination of
      information and reproducibility of protocols, it is important to agree upon
      nomenclature and reach a consensus on documentation of experimental methods and
      procedures. This paper offers recommendations and requirements for reporting on
      applications of electric pulse delivery for electroporation of biological samples
      in life science.

PMID- 29571035
TI  - Prevalence and age-wise distribution of Human Papillomavirus type 16/18
      infections among hospital screened women of a peri-urban area in West Bengal:
      Impact of socio-demographic factors.
AB  - BACKGROUND: We undertook the current study on cervical Human Papillomavirus (HPV)
      prevalence along with cytology in women visiting the Gynecology Out-patient
      Department of a hospital for common gynecological ailments, subsequent to our
      earlier population-based study on HPV prevalence from India. METHODS: We analyzed
      data on cervical-cytology (Pap smears) and PCR-based molecular detection of HPV
      infection along with socio-demographic variables (N = 696). RESULTS: We
      identified 36.84% HPV-positive women amongst whom, HPV16 and 18 together
      predominated (79.37%) over other HPV types (20.63%). Contrarily, only 6.4% women
      revealed abnormal cytological lesions, of which, 46.51% were HPV-positive and 95%
      of such women harbored HPV16/18, while 5% harbored other HPV types. Individuals
      with normal cytology portrayed 36.09% HPV infections, of which, 77.97% were
      HPV16/18-positive and 22.03% harbored other HPV types. Overall HPV prevalence
      decreased significantly (ptrend  = 0.047) with increase in age, but HPV16/18
      infections were significantly over-represented compared to the other HPV types
      across all age-groups. Specifically, HPV16 prevalence increased (p trend < 0.01)
      with increase in severity of cervical lesions. HPV16 prevalence did not differ
      between the Hindus and Muslims but HPV18 was significantly higher among the
      cytologically normal Muslim women (24.14%, p = 0.02), compared to the Hindus
      (11.91%), specifically among those >= 30 years of age. There was a significant (p
      < 0.05) overrepresentation of HPV16 prevalence among women who were users of oral
      contraceptive-pills, irrespective of cytology. CONCLUSIONS: Our study highlights
      the need for HPV16/18-based screening of cervical cancers in India considering
      the immense socio-cultural and genetic diversity at the population level.

PMID- 29571036
TI  - Self organizing map neural networks approach for lithologic interpretation of
      nuclear and electrical well logs in basaltic environment, Southern Syria.
AB  - An approach based on self organizing map (SOM) artificial neural networks is
      proposed herewith oriented towards interpreting nuclear and electrical well
      logging data. The well logging measurements of Kodana well in Southern Syria have
      been interpreted by applying the proposed approach. Lithological cross-section
      model of the basaltic environment has been derived and four different kinds of
      basalt have been consequently distinguished. The four basalts are hard massive
      basalt, hard basalt, pyroclastic basalt and the alteration basalt products- clay.
      The results obtained by SOM artificial neural networks are in a good agreement
      with the previous published results obtained by other different techniques. The
      SOM approach is practiced successfully in the case study of the Kodana well
      logging data, and can be therefore recommended as a suitable and effective
      approach for handling huge well logging data with higher number of variables
      required for lithological discrimination purposes.

PMID- 29571037
TI  - 64Cu, a powerful positron emitter for immunoimaging and theranostic: Production
      via natZnO and natZnO-NPs.
AB  - 64Cu is one of the most beneficial radionuclide that can be used as a theranostic
      agent in Positron Emission Tomography (PET) imaging. In this current work, 64Cu
      was produced with zinc oxide nanoparticles (natZnONPs) and zinc oxide powder
      (natZnO) via the 64Zn(n,p)64Cu reaction in Tehran Research Reactor (TRR) and the
      activity values were compared with each other. The theoretical activity of 64Cu
      also was calculated with MCNPX-2.6 and the cross sections of this reaction were
      calculated by using TALYS-1.8, EMPIRE-3.2.2 and ALICE/ASH nuclear codes and were
      compared with experimental values. Transmission Electronic Microscopy (TEM),
      Scanning Electronic Microscopy (SEM) and X-Ray Diffraction (XRD) analysis were
      used for samples characterizations. From these results, it's concluded that 64Cu
      activity value with nanoscale target was achieved more than the bulk state target
      and had a good adaptation with the MCNPX result.

PMID- 29571038
TI  - A trithiol bifunctional chelate for 72,77As: A matched pair theranostic complex
      with high in vivo stability.
AB  - INTRODUCTION: Trithiol chelates are suitable for labeling radioarsenic (72As:
      2.49 MeV beta+, 26 h; 77As: 0.683 MeV beta-, 38.8 h) to form potential
      theranostic radiopharmaceuticals for PET imaging and therapy. To investigate the
      in vivo stability of trithiol chelates complexed with no carrier added (nca)
      radioarsenic, a bifunctional trithiol chelate was developed, and conjugated to
      bombesin(7-14)NH2 as a model peptide. METHODS: A trithiol-BBN(7-14)NH2
      bioconjugate and its arsenic complex were synthesized and characterized. The
      trithiol-BBN(7-14)NH2 conjugate was radiolabeled with 77As, its in vitro
      stability assessed, and biodistribution studies were performed in CF-1 normal
      mice of free [77As]arsenate and 77As-trithiol- BBN(7-14)NH2. RESULTS: The
      trithiol-BBN(7-14)NH2 conjugate, its precursors and its As-trithiol-BBN(7-14)NH2
      complex were fully characterized. Radiolabeling studies with nca 77As resulted in
      over 90% radiochemical yield of 77As-trithiol-BBN, which was stable for over 48
      h. Biodistribution studies were performed with both free [77As]arsenate and Sep
      Pak(r) purified 77As-trithiol-BBN(7-14)NH2. Compared to the fast renal clearance
      of free [77As]arsenate, 77As-trithiol-BBN(7-14)NH2 demonstrated increased
      retention with clearance mainly through the hepatobiliary system, consistent with
      the lipophilicity of the 77As-trithiol-BBN(714)NH2 complex. CONCLUSION: The
      combined in vitro stability of 77As-trithiol-BBN(7-14)NH2 and the biodistribution
      results demonstrate its high in vivo stability, making the trithiol a promising
      platform for developing radioarsenic-based theranostic radiopharmaceuticals.

PMID- 29571039
TI  - Interleukin 35: Inhibitory regulator in monocyte-derived dendritic cell
      maturation and activation.
AB  - IL-35, a novel IL-12 family member, is a potent inhibitory cytokine predominantly
      produced by regulatory T and B lymphocytes that exerts optimal suppression in
      immune response. However, it remains unclear whether IL-35 plays an inhibitory
      role on human dendritic cells. In the present study, we focused on the possible
      immunosuppressive effect of IL-35 on the differentiation, maturation and function
      of monocyte-derived DCs (MoDCs). Addition of exogenous IL-35 was able to
      partially suppress MoDCs differentiation in vitro. Subsequently, LPS was used for
      the maturation of MoDCs and IL-35 was found to mainly restrain the maturation of
      MoDCs, characterized by the remarkable down-regulation of costimulatory
      molecules, CD83 and HLA-DR as well as a reduced production of pro-inflammatory
      cytokines (IL-12p70, IFN-gamma, and TNF-alpha). Furthermore, IL-35-treated MoDCs
      exhibited strong inhibition in the proliferation of allogeneic CD4+/CD8+ T
      lymphocytes. Meanwhile, IL-35-treated MoDCs also suppressed the polarization of
      naive CD4+ T lymphocytes towards Th1 phenotype and impaired CD8+ T cells
      allogeneic responses. And the foregoing suppression of MoDCs maturation and
      function by IL-35 might be due to the aberrant activation of STAT1/STAT3 and
      inhibition of p38 MAPK/NF-kappaB signaling pathway. Our results demonstrated for
      the first time that IL-35 played a critical role in modulating not only adaptive
      immune response, but also innate immune response. The inhibitory effect of IL-35
      on MoDCs maturation and function may facilitate the development of promising
      therapeutic interventions in tumors and other diseases.

PMID- 29571040
TI  - Different concentration of human cord blood HMGB1 according to delivery and
      labour: A pilot study.
AB  - OBJECTIVE: Oxidative stress is involved in several maternal conditions
      characterized both by an increase in free radicals synthesis and a parallel
      decrease in the antioxidant activity. Parturition induces considerable oxidative
      stress and many inflammatory mediators, among which HMGB1, are involved from the
      beginning of pregnancy to the birth of the infant. We evaluated serum cord blood
      HMGB1 levels in a population of neonates to investigate correlation with mode of
      delivery, as well as the influence of labour. SETTING AND PATIENTS: The study
      subjects were 325 neonates delivered at University Hospital "G. Martino" of
      Messina over an 18-month period. Following cord separation, venous blood sampling
      was performed on umbelical cords. RESULTS: In the cord venous blood, we found
      HMGB1 values significantly more elevated in spontaneous vaginal group when
      compared to elective or emergency caesarean section group. Regarding labour,
      umbilical cord venous blood HMGB1 levels were significantly higher in the
      spontaneous and induced labour group, compared to non-labouring women.
      CONCLUSION: These results could highlight a possible role of HMGB1 during birth
      time related to mode of delivery and labour.

PMID- 29571041
TI  - Microalgae-mediated bioremediation and valorization of cattle wastewater
      previously digested in a hybrid anaerobic reactor using a photobioreactor:
      Comparison between batch and continuous operation.
AB  - Scenedesmus obliquus (ACOI 204/07) microalgae were cultivated in cattle
      wastewater in vertical alveolar flat panel photobioreactors, operated in batch
      and continuous mode, after previous digestion in a hybrid anaerobic reactor. In
      batch operation, removal efficiencies ranges of 65 to 70% of COD, 98 to 99% of
      NH4+ and 69 to 77.5% of PO4-3 after 12days were recorded. The corresponding
      figures for continuous flow were from 57 to 61% of COD, 94 to 96% of NH4+ and 65
      to 70% of PO4-3 with mean hidraulic retention time of 12days. Higher rates of CO2
      fixation (327-547mgL-1d-1) and higher biomass volumetric productivity (213-358mgL
      1d-1) were obtained in batch mode. This microalgae-mediated process can be
      considered promising for bioremediation and valorization of effluents produced by
      cattle breeding yielding a protein-rich microalgal biomass that could be
      eventually used as cattle feed.

PMID- 29571042
TI  - Comparing different methods for determining forest evapotranspiration and its
      components at multiple temporal scales.
AB  - Accurately estimating forest evapotranspiration and its components is of great
      importance for hydrology, ecology, and meteorology. In this study, a comparison
      of methods for determining forest evapotranspiration and its components at
      annual, monthly, daily, and diurnal scales was conducted based on in situ
      measurements in the subhumid mountainous forest of North China. The goal of the
      study was to evaluate the accuracies and reliabilities of the different methods.
      The results indicate the following: (1) The sap flow upscaling procedure, taking
      into account diversities in forest types and tree species, produced component
      based forest evapotranspiration estimate that agreed with eddy covariance-based
      estimate at the temporal scales of year, month, and day, while soil water budget
      based forest evapotranspiration estimate was also qualitatively consistent with
      eddy covariance-based estimate at the daily scale; (2) At the annual scale,
      catchment water balance-based forest evapotranspiration estimate was
      significantly higher than eddy covariance-based estimate, which might probably
      result from non-negligible subsurface runoff caused by the widely distributed
      regolith and fractured bedrock under the ground; (3) At the sub-daily scale, the
      diurnal course of sap flow based-canopy transpiration estimate lagged
      significantly behind eddy covariance-based forest evapotranspiration estimate,
      which might physiologically be due to stem water storage and stem hydraulic
      conductivity. The results in this region may have much referential significance
      for forest evapotranspiration estimation and method evaluation in regions with
      similar environmental conditions.

PMID- 29571043
TI  - Transposon control mechanisms in telomere biology.
AB  - The ends of linear eukaryotic chromosomes, telomeres, are elongated by reverse
      transcriptase activity provided by the enzyme telomerase, or by specialized
      telomeric retrotransposons. Telomerase and telomeric retrotransposons represent
      unique examples of structurally different, but evolutionary and functionally
      related machineries that generate essential chromosome structures, namely
      telomeres. In fact, the telomere is an example of the taming of retroelements for
      the maintenance of essential genome function. Many features of telomere
      homeostasis are conserved between telomerase and retrotransposon maintained
      telomeres. The retrotransposon origin of telomeres suggests that mechanisms of
      transposon control could be adopted for telomere regulation. The discovery of the
      role of Drosophila telomeric piRNAs in telomere length control and the influence
      of LINE-1 retroelements on telomere regulation in human cells strongly support
      this idea and allow us to look at telomere regulation from a new angle.

PMID- 29571044
TI  - Duplication of host genes by transposable elements.
AB  - The availability of large amounts of genomic and transcriptome sequences have
      allowed systematic surveys about the host gene sequences that have been
      duplicated by transposable elements. It is now clear that all super-families of
      transposons are capable of duplicating genes or gene fragments, and such
      incidents have been detected in a wide spectrum of organisms. Emerging evidence
      suggests that a considerable portion of them function as coding or non-coding
      sequences, driving innovations at molecular and phenotypic levels. Interestingly,
      the duplication events not only have to occur in the reproductive tissues to
      become heritable, but the duplicated copies are also preferentially expressed in
      those tissues. As a result, reproductive tissues may serve as the 'incubator' for
      genes generated by transposable elements.

PMID- 29571045
TI  - The benefits and pitfalls of post-mortem computed tomography in forensic external
      examination: A retrospective study of 145 cases.
AB  - OBJECTIVE: Nowadays, post-mortem computed tomography (PMCT) has become an
      integral part of Forensic practice. The purpose of the study was to determine
      PMCT impact on diagnosis of the cause of death within the context of the external
      examination of the body, when autopsy has, at first, not been requested. MATERIAL
      AND METHODS: We reviewed the records of 145 cases for which unenhanced PMCT was
      performed in addition to the external examination of the body from January 2014
      to July 2015 at the Institute of Forensic medicine in Strasbourg (France). We
      confronted final reports from forensic pathologist to the corresponding PMCT
      reports. Data were collected in a contingency table and the impact of PMCT on the
      final conclusions of the forensic pathologist was evaluated via a Chi2 test.
      RESULTS: PMCT results significantly impact the final conclusions of forensic
      pathologist (p<0,001). In some cases, PMCT permits etiological diagnosis by
      revealing a cause of death hidden from external examination (mainly natural
      death) or by supporting the clinical findings of the forensic pathologist. In
      other cases (traumatic death), PMCT enables fast and exhaustive lesion
      assessment. Lastly, there are situations where PMCT may be ineffective
      (intoxication, hanging or some natural deaths). CONCLUSION: Performing PMCT
      within the context of the external examination of the body when autopsy has, at
      first, not been requested could bring significant benefits in diagnosing the
      cause of death. The impact of PMCT varies depending on the circumstances of
      death.

PMID- 29571046
TI  - The contributions of Dr. Kathleen K. Sulik to fetal alcohol spectrum disorders
      research and prevention.
AB  - Dr. Kathleen Sulik (Kathy) has spent 35 years studying fetal alcohol syndrome
      (FAS) and fetal alcohol spectrum disorders (FASD). Beginning with her landmark
      1981 Science paper describing the early gestational window when alcohol can cause
      the craniofacial malformations characteristic of FAS, Kathy has contributed a
      vast amount of research furthering our knowledge of FASD. After her seminal work
      that definitively demonstrated that alcohol is the causative factor in FAS, she
      and her lab went on to explore and define the stage-dependent effects of early
      gestational alcohol exposure on the face and brain in numerous different ways
      throughout her career. She explored and discovered numerous mechanisms of
      alcohol's effects on the embryo, as well as describing several genetic factors
      that can modify susceptibility to developmental alcohol exposure. She did not
      restrict her research to the face and brain; her lab described in intricate
      detail the effects of developmental alcohol exposure on many different organs,
      including the heart, ears, kidneys, and limbs. In addition to her research, and
      in conjunction with NIAAA and the National Organization on Fetal Alcohol Syndrome
      (NOFAS), Kathy developed several FASD prevention curricula that are still in use
      today. Finally, as part of her drive to eradicate FAS and FASD, Kathy labored
      tirelessly with public policy makers to change how FASD is viewed by the public,
      how FASD is identified in affected individuals, and how FASD is studied by
      researchers. While no article could fully cover Kathy's contributions to FASD
      research and prevention, or her other contributions to embryology and teratology,
      this review will attempt to illustrate some of the highlights of Kathy's
      remarkable career.

PMID- 29571047
TI  - Enhanced sensitivity to socially facilitating and anxiolytic effects of ethanol
      in adolescent Sprague Dawley rats following acute prenatal ethanol exposure.
AB  - Emerging evidence suggests that deficits in social functioning and social anxiety
      are associated with adolescent alcohol use. Our previous research has shown that
      acute exposure to a high dose of ethanol on gestational day (G) 12 produces
      social alterations in adolescent Sprague Dawley rats. The present study assessed
      whether these social alterations can affect sensitivity to acute ethanol
      challenge during adolescence. Pregnant females were exposed intraperitoneally
      (i.p.) to ethanol (2.5 g/kg followed by 1.25 g/kg in 2 h) or saline on G12, and
      their male and female offspring were tested on postnatal day (P) 42. Rats were
      challenged i.p. with one of four ethanol doses (0, 0.5, 0.75, and 1.0 g/kg), and
      their social behavior was assessed in a modified social interaction test. Social
      alterations associated with prenatal ethanol exposure and indexed via decreases
      of social investigation, social preference, and play fighting were evident in
      males and females challenged with the 0 g/kg ethanol dose. Acute ethanol
      increased social investigation, social preference, and play fighting in animals
      prenatally exposed to ethanol. In contrast, rats prenatally exposed to saline,
      showing no social facilitation, demonstrated significant ethanol-induced (0.75
      and 1.0 g/kg) decreases in social behavior. Given that late adolescents
      demonstrating social alterations induced by prenatal ethanol exposure become
      sensitive to the socially anxiolytic as well as socially facilitating effects of
      acute ethanol, it is possible that the attractiveness of ethanol to these
      adolescents may be based on its ability to alleviate anxiety under social
      circumstances and facilitate interactions with peers.

PMID- 29571048
TI  - Associations among animal, carcass, muscle characteristics, and fresh meat color
      traits in Charolais cattle.
AB  - This study investigated the effects of animal, carcass and muscle characteristics
      on initial color traits of steaks from 887 Charolais cattle. First, the fixed
      factors of year of birth, experiment and sex had strong impacts on color traits.
      From the covariates, increased age lead to intense color (low h*, -1.55 units)
      and darker and vivid meat (high a*, b* and C*: +4.56, +3.41 and +5.61,
      respectively). Increases in fatness score and carcass fat weight were associated
      with increases in a*, b* and C* (redness; +2.90 to +4.06 for a*; yellowness;
      +2.60 to +3.76 for b*; and vividness, +3.87 to +5.49 for C*) and a darker colored
      lean (L*; -1.56 to -3.23). As pH24h increased, a* (less red) and C* (less vivid)
      decreased (-3.06), whereas hue angle increased (+2.69) leading to poorer color.
      The selection of animals for high degree of muscularity or slaughter weight
      resulted in lighter and darker meat, respectively. The studied covariates could
      be used as indicators of Charolais beef color traits.

PMID- 29571050
TI  - Novel angiogenesis therapeutics by redox injectable hydrogel - Regulation of
      local nitric oxide generation for effective cardiovascular therapy.
AB  - Nitric oxide (NO) possesses various functions in cardiovascular diseases;
      however, due to an extremely short half-life and low bioavailability, its
      therapeutic application is limited. In inflamed tissues, overproduced reactive
      oxygen species (ROS) rapidly react with the endogenous NO, reducing its
      bioavailability. Here, we developed a controllable NO-releasing redox injectable
      hydrogel (NO-RIG) formed by the electrostatic crosslinking between the polyion
      complex flower-type micelles composing of functional polymers to scavenge
      overproduced ROS and regulate the local NO expression level simultaneously. After
      the intracardiac injection to mice, NO-RIG converted to gel via physiological
      temperature-responsive character, distributed homogeneously, and retained in the
      myocardial tissue for more than 10 d. Treatment with NO-RIG remarkably decreased
      the infarction size and improved the heart function after myocardial infarction
      when compared to control injectable hydrogels, such as a simple NO-releasing or
      ROS-scavenging injectable gels. We found that NO-RIG treatment significantly
      enhanced the angiogenesis and new blood vessels formation in mice through the
      regulation of the NO sustained release and redox equilibrium. NO-RIG presents
      high potential in preventing and treating cardiovascular diseases.

PMID- 29571051
TI  - Substrate stiffness modulates the multipotency of human neural crest derived
      ectomesenchymal stem cells via CD44 mediated PDGFR signaling.
AB  - Mesenchymal stem cells (MSCs) have been isolated from various mesodermal and
      ectodermal tissues. While the phenotypic and functional heterogeneity of MSCs
      stemming from their developmental origins has been acknowledged, the genetic and
      environmental factors underpinning these differences are not well-understood.
      Here, we investigated whether substrate stiffness mediated mechanical cues can
      directly modulate the development of ectodermal MSCs (eMSCs) from a precursor
      human neural crest stem cell (NCSC) population. We showed that NCSC-derived eMSCs
      were transcriptionally and functionally distinct from mesodermal bone marrow
      MSCs. eMSCs derived on lower substrate stiffness specifically increased their
      expression of the MSC marker, CD44 in a Rho-ROCK signaling dependent manner,
      which resulted in a concomitant increase in the eMSCs' adipogenic and
      chondrogenic differentiation potential. This mechanically-induced effect can only
      be maintained for short-term upon switching back to a stiff substrate but can be
      sustained for longer-term when the eMSCs were exclusively maintained on soft
      substrates. We also discovered that CD44 expression modulated eMSC self-renewal
      and multipotency via the downregulation of downstream platelet-derived growth
      factor receptor beta (PDGFRbeta) signaling. This is the first instance
      demonstrating that substrate stiffness not only influences the differentiation
      trajectories of MSCs but also their derivation from upstream progenitors, such as
      NCSCs.

PMID- 29571049
TI  - Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53
      activating peptide for acute myeloid leukemia therapy.
AB  - Roughly one third of all human cancers are attributable to the functional
      inhibition of the tumor suppressor protein p53 by its two negative regulators
      MDM2 and MDMX, making dual-specificity peptide antagonists of MDM2 and MDMX
      highly attractive drug candidates for anticancer therapy. Two pharmacological
      barriers, however, remain a major obstacle to the development of peptide
      therapeutics: susceptibility to proteolytic degradation in vivo and inability to
      traverse the cell membrane. Here we report the design of a fluorescent lanthanide
      oxyfluoride nanoparticle (LONp)-based multifunctional peptide drug delivery
      system for potential treatment of acute myeloid leukemia (AML) that commonly
      harbors wild type p53, high levels of MDM2 and/or MDMX, and an overexpressed cell
      surface receptor, CD33. We conjugated to LONp via metal-thiolate bonds a
      dodecameric peptide antagonist of both MDM2 and MDMX, termed PMI, and a CD33
      targeted, humanized monoclonal antibody to allow for AML-specific intracellular
      delivery of a stabilized PMI. The resultant nanoparticle antiCD33-LONp-PMI, while
      nontoxic to normal cells, induced apoptosis of AML cell lines and primary
      leukemic cells isolated from AML patients by antagonizing MDM2 and/or MDMX to
      activate the p53 pathway. Fluorescent antiCD33-LONp-PMI also enabled real-time
      visualization of a series of apoptotic events in AML cells, proving a useful tool
      for possible disease tracking and treatment response monitoring. Our studies shed
      light on the development of antiCD33-LONp-PMI as a novel class of antitumor
      agents, which, if further validated, may help targeted molecular therapy of AML.

PMID- 29571052
TI  - Non-eluting, surface-bound enzymes disrupt surface attachment of bacteria by
      continuous biofilm polysaccharide degradation.
AB  - Bacterial colonization and biofilm formation on surfaces are typically mediated
      by the deposition of exopolysaccharides and conditioning protein layers.
      Pseudomonas aeruginosa is a nosocomial opportunistic pathogen that utilizes
      strain-specific exopolysaccharides such as Psl, Pel or alginate for both initial
      surface attachment and biofilm formation. To generate surfaces that resist P.
      aeruginosa colonization, we covalently bound a Psl-specific glycoside hydrolase
      (PslGh) to several, chemically-distinct surfaces using amine functionalization
      (APTMS) and glutaraldehyde (GDA) linking. In situ quartz crystal microbalance
      (QCM) experiments and fluorescence microscopy demonstrated a complete lack of Psl
      adsorption on the PslGh-bound surfaces. Covalently-bound PslGh was also found to
      significantly reduce P. aeruginosa surface attachment and biofilm formation over
      extended growth periods (8 days). The PslGh surfaces showed a ~99.9% (~3-log)
      reduction in surface associated bacteria compared to control (untreated)
      surfaces, or those treated with inactive enzyme. This work demonstrates a non
      eluting 'bioactive' surface that specifically targets a mechanism of cell
      adhesion, and that surface-bound glycoside hydrolase can significantly reduce
      surface colonization of bacteria through local, continuous enzymatic degradation
      of exopolysaccharide (Psl). These results have significant implications for the
      surface design of medical devices to keep bacteria in a planktonic state, and
      therefore susceptible to antibiotics and antimicrobials.

PMID- 29571053
TI  - Functionalized poly(pyrrole-3-carboxylic acid) nanoneedles for dual-imaging
      guided PDT/PTT combination therapy.
AB  - Herein, poly(pyrrole-3-carboxylic acid) (PPyCOOH) nanoneedles with abundant
      carboxyl groups were synthesized by aqueous dispersion polymerization method
      using pyrrole-3-carboxylic acid as conductive polymer monomer. The PPyCOOH
      nanoneedles not only owned good photothermal performance, but also more
      importantly showed enhanced tumor cell uptake efficiency (1.64 fold) compared
      with size and zeta-potential matched nanospheres. After loading photosensitizer
      aluminum phthalocyanine tetrasulfonate (AlPCS4) and modifying with
      poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) onto the
      PPyCOOH nanoneedles, novel nanoneedle complexes (AlPCS4@PPyCONH-PAH-PAA)
      integrating photodynamic therapy (PDT) and photothermal therapy (PTT) were
      successfully fabricated. The as-prepared nanoneedle complexes improved uptake
      efficiency of AlPCS4 both in vitro and in vivo. Moreover, the nanoneedle
      complexes have infrared thermal and fluorescent properties. By combined PDT/PTT
      under the guiding of dual modal imaging, the tumors in mice were completely
      eliminated and no recurrence was observed in 30 days after treatment, indicating
      that PPyCOOH nanoneedles have great potential as a novel drug carrier for
      constructing multifunctional nanoplatform used for cancer treatment.

PMID- 29571054
TI  - Understanding interactions between biomaterials and biological systems using
      proteomics.
AB  - The role that biomaterials play in the clinical treatment of damaged organs and
      tissues is changing. While biomaterials used in permanent medical devices were
      required to passively take over the function of a damaged tissue in the long
      term, current biomaterials are expected to trigger and harness the self
      regenerative potential of the body in situ and then to degrade, the foundation of
      regenerative medicine. To meet these different requirements, it is imperative to
      fully understand the interactions biomaterials have with biological systems, in
      space and in time. This knowledge will lead to a better understanding of the
      regenerative capabilities of biomaterials aiding their design with improved
      functionalities (e.g. biocompatibility, bioactivity). Proteins play a pivotal
      role in the interaction between biomaterials and cells or tissues. Protein
      adsorption on the material surface is the very first event of this interaction,
      which is determinant for the subsequent processes of cell growth,
      differentiation, and extracellular matrix formation. Against this background, the
      aim of the current review is to provide insight in the current knowledge of the
      role of proteins in cell-biomaterial and tissue-biomaterial interactions. In
      particular, the focus is on proteomics studies, mainly using mass spectrometry,
      and the knowledge they have generated on protein adsorption of biomaterials,
      protein production by cells cultured on materials, safety and efficacy of new
      materials based on nanoparticles and the analysis of extracellular matrices and
      extracellular matrix-derived products. In the outlook, the potential and
      limitations of this approach are discussed and mass spectrometry imaging is
      presented as a powerful technique that complements existing mass spectrometry
      techniques by providing spatial molecular information about the material
      biological system interactions.

PMID- 29571055
TI  - Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and
      side effects reduction in chemotherapy by using fullerenol assembled with
      doxorubicin.
AB  - Chemodrugs have been widely used to treat cancer; however, the chemotherapy
      usually leads to serious side effects and failure. Various nanomaterials and
      strategies have been explored for drug delivery to improve the efficacy of
      chemodrugs. One key to loading chemodrugs onto a nano-delivery system is
      enhancement of the encapsulation efficiency, especially for polymeric
      nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of
      eukaryote to package millions of genes in the nucleus wrapping and condensing DNA
      around histones to form chromosomes, here we developed a karyon-like hybrid
      nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with
      reduced side effects. We utilized fullerenol as a "histone", packaged a great
      number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome"
      (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the
      encapsulation efficiency of Dox in the polymeric micelles was increased from ~5%
      to ~79%. What's more, the biomimetic-inspired delivery system significantly
      reduced the chemodrug side effects by utilizing the radical scavenging ability of
      fullerenol. This novel drug-delivery design approach provides useful insights for
      improving the applicability of fullerenol in drug delivery systems for cancer
      therapy.

PMID- 29571056
TI  - De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published in Seizure 50 (2017) 80-82,
      http://dx.doi.org/10.1016/j.seizure.2017.06.011. The duplicate article has
      therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be
      found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 29571057
TI  - Panayiotopoulos syndrome and benign partial epilepsy with centro-temporal spikes:
      A comparative incidence study.
AB  - PURPOSE: To compare the de novo incidence of Panayiotopoulos syndrome (PS, early
      onset childhood occipital epilepsy) and a common epilepsy syndrome, benign
      epilepsy with centro-temporal spikes (BECTS), in children and young people.
      METHODS: The incidence of PS and BECTS was recorded over 16 months in a
      population of children and young people (aged <16 years) living within a specific
      geographic area and epilepsy network within the North West of England and North
      Wales and the catchment area of the tertiary paediatric epilepsy centre. Monthly
      data collection proformas were circulated to the paediatricians and paediatric
      neurologists responsible for the evaluation of epilepsy in children within this
      area. This also included monthly reminders of the electro-clinical criteria for
      these syndromes. EEGs were undertaken in the neurophysiology department of the
      tertiary paediatric epilepsy centre. The departmental EEG database on all <16
      year olds that underwent an EEG during the study period was examined to identify
      additional patients that may not have been reported via a proforma-reporting
      system. RESULTS: The incidence of PS and BECTS was found to be 0.8 and 6.1 per
      100,000 <16 year olds, respectively. The ages at seizure onset and diagnosis were
      similar for BECTS and PS. CONCLUSION: This study is the first to determine a
      comparative incidence of PS and BECTS. The findings suggest BECTS is eight times
      more common than PS and that the incidence of PS is lower than previously
      suggested.

PMID- 29571058
TI  - SJL-1, a C-type lectin, acts as a surface defense molecule in Japanese sea
      cucumber, Apostichopus japonicus.
AB  - The surface defense molecules of aquatic invertebrates against infectious
      microorganisms have remained largely unexplored. In the present study,
      hemagglutinins were isolated from an extract of body surface layer of Japanese
      sea cucumber, Apostichopus japonicus, by affinity chromatography with fixed
      rabbit erythrocyte membranes. The N-terminal sequence of a 15-kDa agglutinin was
      almost identical with that of SJL-1, a C-type lectin formerly identified in this
      species. Because cDNA sequence and tissue distribution of SJL-1 have not been
      reported, we performed cDNA sequencing, gene expression analysis, and western
      blotting and immunohistochemical evaluation with anti-recombinant SJL-1 (rSJL-1)
      antibodies. The hemagglutinin gene was transcribed mainly in the integument,
      tentacles, and respiratory tree. Western blotting revealed that SJL-I is present
      in a body surface rinse, indicating that SJL-1 is secreted onto the body surface.
      SJL-1-positive cells scattered beneath the outermost layer of the integument were
      detected by immunohistochemistry. Furthermore, rSJL-1 agglutinated Gram-positive
      and Gram-negative bacteria, and yeast. These results indicate that SJL-1 acts as
      a surface defense molecule in A. japonicus.

PMID- 29571059
TI  - Relative antibacterial functions of complement and NETs: NETs trap and complement
      effectively kills bacteria.
AB  - Neutrophil extracellular traps (NETs) are web-like DNA structures released by
      activated neutrophils. These structures are decorated with antimicrobial
      proteins, and considered to trap and kill bacteria extracellularly. However, the
      exact functions of NETs remain elusive, and contradictory observations have been
      made with NETs functioning as an antimicrobial or a pathogentrapping mechanism.
      There is a disconnect in the interpretation of the involvement of other major
      immune mechanisms, such as the complement system, as effectors of the function of
      NETs. We have recently shown that NETs activate complement. In this study, we
      aimed to elucidate the relative antimicrobial roles of NETs in the absence and
      presence of complement. Using primary human neutrophils, human serum (normal,
      heat inactivated, and C5-depleted), P. aeruginosa (at multiplicity of infection,
      MOI, of 1 or 10), S. aureus (MOI of 1), colony-counting assays and confocal
      microscopy, we demonstrate that most bacteria trapped by NETs remain viable,
      indicating that NETs have limited bactericidal properties. By contrast,
      complement effectively killed bacteria, but NETs decreased the bactericidal
      ability of complement and degrading NETs by DNases restored complement-mediated
      killing. Experiments with conditions allowing for specific pathway activation
      showed that the complement classical and lectin, but not the alternative, pathway
      lead to bacterial killing. NETs under static conditions showed limited killing of
      bacteria while NETs under dynamic conditions showed enhanced bacteria trapping
      and reduced killing. Furthermore, NETs incubated with normal human serum depleted
      complement and reduced the hemolytic capacity of the serum. This report, for the
      first time, clarifies the relative bactericidal contributions of NETs and
      complement. We propose that - while NETs can ensnare bacteria such as P.
      aeruginosa - complement is necessary for efficient bacterial killing.

PMID- 29571061
TI  - Ingested razor blades within the appendix: A rare case report.
AB  - INTRODUCTION: Foreign body ingestion is a common clinical presentation with less
      than 1% of the cases requiring surgical intervention. In this report, we present
      a rare case of razor blades lodged in the appendix as a result of intentional
      ingestion. PRESENTATION OF CASE: A 25 year old male prisoner presented to our
      hospital with persistent right iliac fossa pain after razor blade ingestion.
      After 5 days of conservative management, there was no sign of transition on
      serial X-Rays. Laparoscopy with intraoperative image intensification confirmed
      the presence of the razor blades in the appendix and appendicectomy was
      subsequently performed without complications. DISCUSSION: Most ingested objected
      with diameter less than 2.5 cm and length less than 6 cm can pass through the
      gastrointestinal tract spontaneously in less than one week. The entry of foreign
      objects into the appendix is thought to be due to relative low motility of the
      caecum, the dependent position of the appendix and the size of the appendiceal
      orifice. Radiographic localisation to the appendiceal lumen was complicated by
      metallic artefact, but was consistent with failure to transit. Appendicectomy was
      felt to be the safest mode of retrieval. CONCLUSION: Ingested foreign body lodged
      in the appendix is a rare event. Once the exact location is confirmed, a simple
      laparoscopic appendicectomy can be performed to facilitate the removal.

PMID- 29571060
TI  - Hypertrophic spinal pachymeningitis associated with human T-cell lymphotrophic
      virus-1 infection and Sjogren's syndrome: A case report and brief literature
      review.
AB  - INTRODUCTION: Reports of hypertrophic spinal pachymeningitis associated with
      human T-cell lymphotrophic virus-1 (HTLV-1) infection and Sjogren's syndrome in
      the English literature are still very rare. PRESENTATION OF CASE: We hereby
      present a case of a 78-year-old female with a history of lower extremity weakness
      after a fall, which fully resolved after conservative treatment. However, the
      symptoms recurred 4 years later, and the patient became unable to walk. The
      patient had no superficial or deep sensation below the level of T9, and she also
      had urinary retention. Magnetic resonance imaging showed that hypertrophic dura
      mater was compressing the spinal cord from T2 to T10. Blood testing revealed
      increased anti-HTLV-1 antibody, rheumatoid factor, elevation of anti-SS-A
      antibody and antinuclear antibody. The cerebrospinal fluid contained markedly
      elevated levels of total protein and cell numbers. Biopsy of the labial gland of
      the lip revealed chronic sialadenitis. DISCUSSION: In collaboration with a
      neurologist, we diagnosed this patient with hypertrophic spinal pachymeningitis
      associated with HTLV-1 infection and Sjogren's syndrome. We performed laminectomy
      at the affected spinal levels, resected the thickened dura, and maintained the
      patient on steroid therapy. The patient attained a marked recovery; she could
      walk with a cane and her urinary retention was improved. CONCLUSION: For the
      management of HSP associated with HTLV-1 and SS, we recommend surgical
      decompression with subsequent prolonged steroid therapy and prolonged close
      monitoring to achieve a good long-term outcome.

PMID- 29571062
TI  - The potentiality of laparoscopic partial liver excisional biopsy using analysis
      of the liver surface based on preoperative 3D simulation imaging: A case report.
AB  - INTRODUCTION: The imaging diagnostics of liver tumor are difficult. There are no
      effective biopsy examinations for liver tumors that cannot be detected even by
      ultrasonography (US) and computed tomography (CT). We report a remarkably useful
      biopsy method for such tumors. PRESENTATION OF CASE: A 67-year-old man with
      hepatitis C underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid
      enhanced magnetic resonance imaging, and the images revealed multiple delayed
      enhanced masses that showed high signal intensity in the hepatobiliary phase. The
      possibility of malignancy could not be ruled out due to the trend towards
      increased size of the masses. Percutaneous liver biopsy was considered impossible
      because CT and US could not detect the masses. Laparoscopic liver biopsy with
      preoperative simulation using 3D imaging was performed. The 3D imaging provided
      accurate information of liver surface irregularities with cirrhosis change. The
      tumor location was confirmed, and adequate tumor excisional biopsy was performed.
      Histological assessment revealed the tumor to be a focal nodular hyperplasia-like
      nodule. DISCUSSION AND CONCLUSIONS: Laparoscopic liver biopsy has been widely
      used because of its safety and accuracy. It enables accurate resection of tumors
      that are undetectable with CT and US by employing preoperative 3D imaging while
      maintaining the less-invasiveness.

PMID- 29571063
TI  - Advantage of laparoscopic resection for pelvic Schwannoma: Case report and review
      of the literature.
AB  - INTRODUCTION: Single pelvic schwannomas are rare tumor arising from the
      retrorectal, lateral or obturatory space. Laparoscopic approach to schwannoma
      located in lateral pelvic space has been previously described only in one case
      report. We present a case of a successful laparoscopic resection of pelvic
      schwannoma emphasizing the advantages of such a minimal invasive approach.
      PRESENTATION OF CASE: A 54-years-old, obese, male patient was admitted to our
      hospital referring dysuria and strangury. Abdominal CT scan showed a lateral
      pelvic well-circumscribed mass with smooth regular margins. A CT-guided fine
      needle biopsy resulted non-diagnostic. An elective laparoscopic resection was
      performed. The patient had a short, uneventful post-operative course.
      Pathological examination revealed a benign schwannoma. DISCUSSION: Using PubMed
      database, we reviewed the English language international literature using the
      MeSH terms "laparoscopic," "minimally invasive" and "schwannoma". We identified
      quite 20 previous cases of pelvic schwannomas removed by laparoscopy or robotic
      surgery. We found out that a preoperative diagnosis of these rare neoplasms is
      difficult to be obtained; in most cases, laparoscopic approach was successfully
      performed. CONCLUSION: Despite it could not be proven yet, due to the rarity of
      this tumor, we agree with literature that laparoscopic removal of pelvic benign
      tumor may offer several advantages. The direct high-definition vision deeply into
      this narrow anatomical space, especially in obese patients, provides a detailed
      view that makes easier to isolate and spear the anatomical structures surrounding
      the tumor. Furthermore, the pneumoperitoneum may create the right plane of
      dissection, minimizing the risk of tumor rupture and bleeding.

PMID- 29571064
TI  - Spontaneous migration of thrombosed synthetic vascular graft to the duodenum
      after living-donor liver transplantation: A case-report.
AB  - INTRODUCTION: Spontaneous migration of synthetic grafts had been described after
      abdominal vascular procedures into the duodenum and small bowel. In the setting
      of liver transplantation, synthetic grafts are commonly used for overcoming
      shortened or poor-quality vasculatures. We describe a case of spontaneous
      migration of thrombosed synthetic vascular graft after living-donor liver
      transplantation (LDLT). PRESENTATION: A 59 years male patient with end stage
      liver disease underwent LDLT utilizing a right hemi-liver graft. Drainage of
      segment V vein was done to inferior vena cava using a vascular graft. Graft
      patency was confirmed by regular follow up doppler ultrasound. Graft thrombosis
      was detected on the 4th postoperative month. The patient developed anastomotic
      biliary stricture 3 months after LDLT, which required repeated endoscopic
      retrograde cholangio-pancreatography (ERCP). During an ERCP set two and half
      years after LDLT, the thrombosed graft was seen eroding into the first part of
      the duodenum. The patient was generally stable and the decision was to follow up
      the condition. Follow up computed tomography showed disappearance of the graft
      from the abdomen, and endoscopy revealed a small ulcer at the site of the
      migrated graft. DISCUSSION: Reports regarding spontaneous migration of synthetic
      grafts in this setting of LDLT are extremely rare. We report a rare case of
      spontaneous migration of thrombosed synthetic vascular graft into the duodenum
      after LDLT. CONCLUSION: We report a rare case of spontaneous migration of
      thrombosed synthetic vascular graft into the duodenum after LDLT.

PMID- 29571065
TI  - A rare case report of Morgagni Hernia with Organo-Axial Gastric Volvulus and
      concomitant Para-esophageal hernia, repaired laparoscopically in a
      Septuagenarian.
AB  - INTRODUCTION: Simultaneous occurrence of Morgagni and the Para-esophageal hernia
      is a rare clinical condition with eight case reports in the English-language
      literature and only four managed laparoscopically. We describe a case of a
      Septuagenarian patient with Morgagni and concomitant Para-esophageal hernia
      treated laparoscopically. PRESENTATION OF A CASE: A 71-year-old male patient,
      presented with a one-month history of regurgitation of acid, retrosternal burning
      and vomiting after eating. Computed tomography (CT) imaging demonstrated a large
      anterior diaphragmatic hernia, with herniation of bowel loops and anterosuperior
      displacement of the gastric antrum along with a grade III Para-esophageal hernia.
      The patient underwent simultaneous laparoscopic repair of Morgagni and Para
      esophageal hernia with mesh reinforcement with Nissen's total anti-reflux
      fundoplication. The patient's postoperative recovery was uneventful. DISCUSSION:
      A Morgagni Hernia is a rare congenital condition consisting of a Subcosto-sternal
      defect in the diaphragm. A Para-esophageal hernia is a rare variant of a hiatus
      hernia. Morgagni and Para-esophageal hernia may present with gastric volvulus or
      incarceration, requiring emergency treatment. Minimally invasive surgery is the
      preferred treatment, particularly for elderly patients and patients with
      comorbidities. The laparoscopic operation can provide excellent exposure and
      repair the hernia defect easily with minimal invasiveness and fewer
      complications. CONCLUSION: This case report highlights the co-existence of
      Morgagni and Para-esophageal hernias and validates the feasibility of
      laparoscopic repair of both hernias simultaneously.

PMID- 29571066
TI  - In vitro and in vivo evaluation of the bifunctional chelator NODIA-Me in
      combination with a prostate-specific membrane antigen targeting vector.
AB  - INTRODUCTION: We recently developed a chelating platform based on the macrocycle
      1,4,7-triazacyclononane with up to three five-membered azaheterocyclic arms for
      complexation of the PET nuclides gallium-68 and copper-64. The main objective of
      this study was to evaluate the stability and pharmacokinetics of 68Ga- and 64Cu
      complexes of the bifunctional chelator NODIA-Me 1 covalently bound to a PSMA
      targeting vector in vivo. METHODS: NODIA-Me 1 was conjugated to the PSMA
      targeting Glu-NH-CO-NH-Lys moiety to give the bioconjugate NODIA-Me-NaI-Ahx-PSMA
      4. The stability of [68Ga]4 and [64Cu]4 was assessed in vitro by serum stability
      studies. The PSMA binding affinity was determined in competitive cell experiments
      in LNCaP cells using 68Ga-PSMA-HBED-CC as radioligand. The stability and
      pharmacokinetics of [68Ga]4 and [64Cu]4 was evaluated by PET imaging and ex vivo
      biodistribution studies in mice bearing subcutaneous LNCaP tumors. RESULTS: In
      human serum, [68Ga]4 and [64Cu]4 remained intact to 85% (3 h) and 92% (24 h),
      respectively. Nature of the metal chelate influenced PSMA binding affinity with
      IC50 of 233 +/- 10 nM for uncomplexed 4, 681 +/- 7 nM for Cu-4 and 176 +/- 10 nM
      for Ga-4. In animal studies, [68Ga]4 and [64Cu]4 revealed low uptake (<=1% IA g
      1) in the majority of organs. Kidney uptake at 1 h p.i. was 6.28 +/- 0.92% IA g-1
      and 4.96 +/- 0.79% IA g-1 and specific tumor uptake was 1.33 +/- 0.46% IA g-1 and
      2.15 +/- 0.38% IA g-1 for [68Ga]4 and [64Cu]4, respectively. CONCLUSION: The
      bifunctional chelator NODIA-Me 1 was successfully conjugated to a PSMA targeting
      moiety. In small-animal PET imaging and ex vivo biodistribution studies, 68Ga-
      and 64Cu-labelled conjugates specifically delineated PSMA-positive LNCaP tumors
      and exhibited rapid renal clearance from non-target tissues with no significant
      demetallation/transchelation in vivo. The results support further development of
      this novel chelating platform for production of 68Ga- and 64Cu-labelled
      radiopharmaceuticals.

PMID- 29571067
TI  - Evaluation of 177Lu[Lu]-CHX-A"-DTPA-6A10 Fab as a radioimmunotherapy agent
      targeting carbonic anhydrase XII.
AB  - INTRODUCTION: Due to their infiltrative growth behavior, gliomas have, even after
      surgical resection, a high recurrence tendency. The approach of intracavitary
      radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly
      administering drugs into the resection cavity (RC). Direct application of the
      radioconjugate into the RC has the advantage of bypassing the blood-brain
      barrier, which allows the administration of higher radiation doses than systemic
      application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells
      while being absent from normal brain and thus an attractive target molecule for
      RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled
      with 177Lu as an agent for RIT. METHODS: 6A10 Fab fragment was modified and
      radiolabelled with 177Lu and characterized by MALDI-TOF, flow cytometry and radio
      TLC. In vitro stability was determined under physiological conditions.
      Biodistribution studies, autoradiography tumor examinations and planar
      scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts.
      RESULTS: The in vitro CA XII binding capacity of the modified Fab was confirmed.
      Radiochemical purity was determined to be >90% after 72 h of incubation under
      physiological conditions. Autoradiography experiments proved the specific binding
      of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor
      uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to
      contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy.
      CONCLUSION: The radiochemical stability in combination with a successful in vivo
      tumor uptake shows the potential suitability for future RIT applications with the
      6A10 Fab.

PMID- 29571068
TI  - Robust high-yield ~1 TBq production of cyclotron based sodium
      [99mTc]pertechnetate.
AB  - : This paper presents the irradiation and processing of high-current 100Mo
      targets at the University of Alberta (UofA) in a GMP compliant setting. For
      purpose of comparison with a second production facility, additional studies at
      Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described.
      INTRODUCTION: More than 70% of today's diagnostic radiopharmaceuticals are based
      on 99mTc, however the conventional supply chain for obtaining 99mTc is fragile.
      The aim of this work was to demonstrate reliable high yield production and
      processing of 99mTc with medium-energy, high-current, cyclotrons. METHODS: We
      used two cyclotrons (TR-24, Advanced Cyclotron Systems, Inc) for irradiations
      with 22 MeV or 24 MeV incident energy and 400 MUA current up to a maximum of 6 h.
      The irradiated 100Mo was dissolved using peroxide, basified using ammonium
      carbonate, and purified using a PEG-based solid phase extraction technique.
      RESULTS: High-yield productions with 22 MeV (400 MUA, 6 h) yielded an average
      isolated [99mTc]TcO4- yield of 878 GBq +/- 99 GBq (23.7 Ci +/- 2.7 Ci) decay
      corrected to EOB, n = 8 (isolated saturation yield: 4.36 +/- 0.49 GBq/MUA).
      Irradiations with 24 MeV (400 MUA, 6 h) resulted in an average isolated
      [99mTc]TcO4- yield of 993 GBq +/- 100 GBq (26.8 Ci +/- 2.7 Ci) decay corrected to
      EOB, n = 7 (isolated saturation yield: 4.97 +/- 0.50 GBq/MUA). These yields
      corresponds to 600-700 GBq (16-19 Ci) of [99mTc]TcO4- at release (i.e. 3 hour
      post-EOB). For all tested batches, the QC results were within the recently
      published specifications in the European Pharmacopoeia. CONCLUSION: Reliable near
      TBq production yields for 99mTc can be obtained using medium-energy cyclotrons.
      ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This work presents
      evidence that medium-energy high-current cyclotrons can provide high yields of
      [99mTc]TcO4- with radionuclidic impurities levels within the specifications of
      the existing European Pharmacopoeia monograph, indicating that this technology
      can have a share in the future 99mTc supply market.

PMID- 29571069
TI  - Tissue and cellular mechanics of seeds.
AB  - Distinct plant seed/fruit structures evolved to support reproduction and
      dispersal in distinct environments. Appropriate biomechanical properties and
      interactions of the various seed compartments are indispensable to plant
      survival. Most seeds are dispersed in a dry state generated during seed
      development/maturation for which novel aspects of endosperm-embryo interaction
      were discovered. The various layers covering the embryo of a mature seed define
      the patterns of water uptake during germination. Their biomechanical weakening
      together with embryo cell expansion is mediated by cell wall remodelling to
      facilitate radicle protrusion. Recent work with different species has revealed
      mechanisms underpinning specific embryo growth zones. Abiotic and biotic factors
      were shown to release different types of seed and fruit coat-mediated constraints
      to water uptake and germination.

PMID- 29571070
TI  - Effect of pterin impurities on the fluorescence and photochemistry of commercial
      folic acid.
AB  - Folic acid, or pteroyl-l-glutamic acid (PteGlu) is a conjugated pterin derivative
      that is used in dietary supplementation as a source of folates, a group of
      compounds essential for a variety of physiological functions in humans.
      Photochemistry of PteGlu is important because folates are not synthesized by
      mammals, undergo photodegradation and their deficiency is related to many
      diseases. We have demonstrated that usual commercial PteGlu is unpurified with
      the unconjugated oxidized pterins 6-formylpterin (Fop) and 6-carboxypterin (Cap).
      These compounds are in such low amounts that a normal chromatographic control
      would not detect any pterinic contamination. However, the fluorescence of PteGlu
      solutions is due to the emission of Fop and Cap and the contribution of the
      PteGlu emission, much lower, is negligible. This is because the fluorescence
      quantum yield (PhiF) of PteGlu is extremely weak compared to the PhiF of Fop and
      Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation
      photosensitized by oxidized unconjugated pterins present in the solution, and not
      a process initiated by the direct absorption of photons by PteGlu. In brief, the
      fluorescence and photochemical properties of PteGlu solutions, prepared using
      commercially available solids, are due to their unconjugated pterins impurities
      and not to PteGlu itself. This fact calls into question many reported studies on
      fluorescence and photooxidation of this compound.

PMID- 29571071
TI  - Differences between attached and suspended microalgal cells in ssPBR from the
      perspective of physiological properties.
AB  - Attached microalgae cultivation for the algae-based products is considered as a
      promising approach to simplify biomass recovery processes and reduce the cost.
      However, as an incipient research field, biomass accumulation is the mainly index
      for attached microalgal growth evaluation. To break through such limitations,
      physiological properties of attached microalgae (e.g. the oxygen evolving
      activity and the main organic composition of cells), which are important for
      microalgal growth evaluation but are still unclear in most studies, were studied
      using an attached microalgae culture system, i.e. suspended-solid phase
      photobioreactor (ssPBR) in this paper. As light, nutrients and other
      environmental conditions of attached microalgae were different from the suspended
      microalgae, physiological properties of attached microalgae also varied from the
      suspended ones. Besides the relatively lower biomass accumulation rate, attached
      microalgae also had a lower oxygen evolving activity (65% on average) comparing
      to suspended microalgae. The composition of microalgae changed towards
      accumulating more protein when suspended microalgae turned to attached status.
      The relative protein content of attached microalgae (50.1% +/- 10.1%) was
      approximately 30% higher than the suspended algae (36.0% +/- 16.1%) on average.
      The discovery of physiological properties of attached microalgae in this paper
      could help the production of high-protein microalgae-related products and explain
      some phenomenon during the production of microalgae-related products.

PMID- 29571072
TI  - European Psychiatric Association (EPA) guidance on forensic psychiatry: Evidence
      based assessment and treatment of mentally disordered offenders.
AB  - Forensic psychiatry in Europe is a specialty primarily concerned with individuals
      who have either offended or present a risk of doing so, and who also suffer from
      a psychiatric condition. These mentally disordered offenders (MDOs) are often
      cared for in secure psychiatric environments or prisons. In this guidance paper
      we first present an overview of the field of forensic psychiatry from a European
      perspective. We then present a review of the literature summarising the evidence
      on the assessment and treatment of MDOs under the following headings: The
      forensic psychiatrist as expert witness, risk, treatment settings for mentally
      disordered offenders, and what works for MDOs. We undertook a rapid review of the
      literature with search terms related to: forensic psychiatry, review articles,
      randomised controlled trials and best practice. We searched the Medline, Embase,
      PsycINFO, and Cochrane library databases from 2000 onwards for adult groups only.
      We scrutinised publications for additional relevant literature, and searched the
      websites of relevant professional organisations for policies, statements or
      guidance of interest. We present the findings of the scientific literature as
      well as recommendations for best practice drawing additionally from the guidance
      documents identified. We found that the evidence base for forensic-psychiatric
      practice is weak though there is some evidence to suggest that psychiatric care
      produces better outcomes than criminal justice detention only. Practitioners need
      to follow general psychiatric guidance as well as that for offenders, adapted for
      the complex needs of this patient group, paying particular attention to long-term
      detention and ethical issues.

PMID- 29571073
TI  - Concurrent Treatment with Anti-DLL4 Enhances Antitumor and Proapoptotic Efficacy
      of a gamma-Secretase Inhibitor in Gastric Cancer.
AB  - The Notch signaling pathway has been identified as a therapeutic target for
      cancers. gamma-Secretase inhibitors (GSIs) have been progressively recognized as
      potential anticancer drugs. The present study aimed to investigate the effects of
      anti-delta like legend 4 (anti-DLL4) treatment on the anticancer efficacy of GSIs
      in gastric cancer. SGC-7901-GFP human gastric cancer cells were tested for DLL4
      expression by rosette formation test and immunofluorescence, and then were
      treated with anti-DLL4 antibody N-[N-(3,5-difluorophenacetyl)-L-ananyl]-S
      phenylglycine t-butyl ester (DAPT, a type of GSI), or a combination of anti-DLL4
      antibody and DAPT. The effects of in vitro treatments on cell apoptosis, cell
      cycle, and cell invasion were analyzed. For in vivo study, an orthotopic mouse
      model of gastric cancer was established with green fluorescence expressing SGC
      7901. Ultrasound targeted microbubble destruction was used to treat tumor-bearing
      mice with anti-DLL4 antibody conjugated microbubbles, DAPT, and a combination of
      the two. Real-time fluorescence imaging was performed to assess tumor cell
      inhibition in each group. Following in vivo treatments, apoptosis of tumor cells
      and the expression of apoptosis-related genes BAX, Bcl-2, and P53 were detected
      by TUNEL and immunohistochemical staining. In vivo combined treatment of anti
      DLL4 and DAPT led to a higher rate of cell apoptosis and greater inhibition of
      cell invasion than that observed with DAPT treatment alone. DAPT and anti-DLL4
      combination therapy resulted in decreased cell distribution at G1 phase and
      increased cell distribution at S phase, compared to the untreated control group
      (P < .01). In vivo combined therapy with anti-DLL4 and DAPT significantly
      increased tumor growth inhibition and tumor cell apoptosis when compared to DAPT
      therapy alone (P < .05). In addition, combined treatment significantly increased
      expression of BAX and P53 and reduced Bcl-2 expression (P < .05). Conversely,
      treatment with DAPT alone only increased expression of BAX and P53 (P < .05),
      suggesting that the reduction of Bcl-2 expression may play an important role in
      the synergetic antitumor and proapoptosis effects of the combined treatment.
      Concurrent treatment with anti-DLL4 enhances the antitumor and proapoptotic
      efficacy of the gamma-secretase inhibitor in gastric cancer both in vitro and in
      vivo.

PMID- 29571074
TI  - Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation
      Personalized Treatment.
AB  - Malignant gliomas are heterogeneous diseases in genetic basis. The development of
      sequencing techniques has identified many gene rearrangements encoding novel
      oncogenic fusions in malignant glioma to date. Understanding the gene fusions and
      how they regulate cellular processes in different subtypes of glioma will shed
      light on genomic diagnostic approaches for personalized treatment. By now,
      studies of gene fusions in glioma remain limited, and no medication has been
      approved for treating the malignancy harboring gene fusions. This review will
      discuss the current characterization of gene fusions occurring in both adult and
      pediatric malignant gliomas, their roles in oncogenesis, and the potential
      clinical implication as therapeutic targets.

PMID- 29571075
TI  - Elevated body-mass index is associated with reduced white matter integrity in two
      large independent cohorts.
AB  - Obesity has been associated with a variety of neurobiological alterations. Recent
      neuroimaging research has pointed to the relevance of brain structural and
      functional alterations in the development of obesity. However, while the role of
      gray matter atrophy in obesity has been evidenced in several well powered
      studies, large scale evidence for altered white matter integrity in obese
      subjects is still absent. With this study, we therefore aimed to investigate
      potential associations between white matter abnormalities and body mass index
      (BMI) in two large independent samples of healthy adults. Associations between
      BMI values and whole brain fractional anisotropy (FA) were investigated in two
      independent cohorts: A sample of n = 369 healthy subjects from the Munster
      Neuroimaging Cohort (MNC), as well as a public available sample of n = 1064
      healthy subjects of the Humane Connectome Project (HCP) were included in the
      present study. Tract based spatial statistics (TBSS) analyses of BMI on whole
      brain FA were conducted including age and sex as nuisance covariates using the
      FMRIB library (FSL Version 5.0). Threshold-free cluster enhancement was applied
      to control for multiple comparisons. In both samples higher BMI was significantly
      associated with strong and widespread FA reductions. These effects were most
      pronounced in the corpus callosum, bilateral posterior thalamic radiation,
      bilateral internal capsule and external capsule, bilateral inferior longitudinal
      fasciculus and inferior fronto-occipital fasciculus. The association was found to
      be independent of age, sex and other cardiovascular risk factors. No significant
      positive associations between BMI and FA occurred. With this highly powered
      study, we provide robust evidence for globally reduced white matter integrity
      associated with elevated BMI including replication in an independent sample. The
      present work thus points out the relevance of white matter alterations as a
      neurobiological correlate of obesity.

PMID- 29571077
TI  - Neonates with congenital Cytomegalovirus and hearing loss identified via the
      universal newborn hearing screening program.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) is the most common non-genetic cause
      of sensorineural hearing loss. Currently, there are no universal CMV screening
      programs for newborns or routine CMV testing of neonates with hearing loss in
      Australia, or elsewhere. OBJECTIVES: This study was undertaken to determine the
      prevalence of congenital CMV infection in infants with hearing loss identified
      using routine resources via the Australian universal neonatal hearing screening
      (UNHS) program. STUDY DESIGN: Infants who failed UNHS, referred for audiological
      testing and found to have permanent hearing loss were screened for CMV via PCR of
      urine and saliva. Congenital CMV was diagnosed if CMV was detected in infants
      <=30 days of age, or using retrospective testing on stored new born screening
      cards, retrospective testing, or using clinical criteria if >30 days of age. The
      cohort was analyzed for time of testing and prevalence of congenital CMV
      determined. RESULTS: The Audiology Department reviewed 1669 infants who failed
      UNHS between 2009 and 2016. Thirty percent (502/1669) had permanent hearing loss
      confirmed, of whom 336/502 were offered CMV testing. A definite (n = 11) or
      probable (n = 8) diagnosis of congenital CMV occurred in 19/323 (5.9%), of whom
      definite diagnoses were made in 4/19 on tests positive prior to 21 days of life,
      in 5/19 who were positive on neonatal blood screening card (NBSC) testing, in
      2/19 who were positive on placental testing. In 8/19 probable diagnoses were made
      based on positive testing between ages 23-42 days and a consistent clinical
      syndrome in the absence of another cause for hearing loss after genetic and other
      testing. CMV testing mirrored the timing of audiological testing, with ~40%
      completing audiology and CMV testing by 21 days, and 64% by 30 days. CONCLUSION:
      This program, utilizing existing clinical services identified probable congenital
      CMV in ~6% of a large cohort failing UNHS with permanent hearing loss, of whom
      more than half were definite diagnoses. No additional assets were required to
      those already existing in this tertiary referral pediatric centre, whilst
      providing useful and timely data for clinical and audiological management.

PMID- 29571078
TI  - Close relation of interpersonal sensitivity with negative core beliefs about the
      self, the central construct of cognitive vulnerability to depression.
AB  - Interpersonal sensitivity is a personality trait linked with anxious attachment
      conceptualized in attachment theory. This personality trait is comprised of four
      components, i.e., interpersonal awareness, separation anxiety, timidity and
      fragile inner-self, which are measured by the corresponding subscales of the
      Interpersonal Sensitivity Measure (IPSM). Meanwhile, one study showed that six
      items of the IPSM tentatively used as negative self-schemas predicted the onset
      of depression. To clarify if interpersonal sensitivity reflects cognitive
      vulnerability, we examined the relation of this personality trait with negative
      core beliefs about the self. The study population consisted of 335 Japanese
      volunteers. Interpersonal sensitivity was measured by the IPSM, and negative core
      beliefs about the self were assessed by the negative-self subscale of the Brief
      Core Schema Scales (BCSS). Multiple regression analysis showed that scores of the
      four subscales of the IPSM were strongly correlated with those of the negative
      self subscale of the BCSS (P < 0.001). Similarly, sequential equation modeling
      demonstrated that the four components of interpersonal sensitivity were strongly
      predicted by core beliefs of negative-self (P < 0.001). The present study shows
      that interpersonal sensitivity is closely related to negative core beliefs about
      the self, suggesting that this personality trait can be regarded as a cognitive
      vulnerability to depression.

PMID- 29571076
TI  - Alcohol research with transgender populations: A systematic review and
      recommendations to strengthen future studies.
AB  - BACKGROUND: There is a recent and growing research literature on alcohol use and
      related harms among transgender and other gender minority populations; however,
      current definitions and measures of hazardous drinking do not consider the
      complexity of physiological sex characteristics and socially constructed gender,
      raising doubts regarding their validity, applicability, and use with these
      populations. To address this, we reviewed current research on alcohol-related
      outcomes in transgender populations and critically summarized key issues for
      consideration in future research. METHODS: We conducted a systematic review of
      transgender alcohol research in English language, peer-reviewed journals,
      published 1990-2017, and extracted key details (e.g., sample composition, alcohol
      measures, results). RESULTS: Forty-four studies met all inclusion criteria for
      the review, the majority of which were conducted in the United States. The
      prevalence of hazardous drinking was high; however, estimates varied widely
      across studies. We noted frequent methodological weaknesses, including few
      attempts to differentiate sex and gender, poor attention to appropriate
      definitions of hazardous drinking, and reliance on cross-sectional study designs
      and non-probability sampling methods. CONCLUSION: Given findings that suggest
      high need for ongoing public health attention, we offer recommendations to
      improve future alcohol studies with transgender and other gender minority
      populations, such as being explicit as to whether and how sex and/or gender are
      operationalized and relevant for the research question, expanding the repertoire
      of alcohol measures to include those not contingent on sex or gender, testing the
      psychometric performance of established screening instruments with transgender
      populations, and shifting from descriptive to analytic study designs.

PMID- 29571079
TI  - Affective startle modulation in young people with first-presentation borderline
      personality disorder.
AB  - This study investigated psychophysiological and subjective emotional responses to
      an affective startle modulation paradigm in first-presentation borderline
      personality disorder (BPD). Twenty BPD and 20 healthy control participants, aged
      15-24 years, viewed a set of standardized pictures with pleasant, neutral, or
      unpleasant valence, and were instructed to either "maintain" or "suppress" their
      emotional response to the stimuli. Despite showing markedly higher levels of
      baseline distress on self-report questionnaires, BPD participants had
      significantly lower skin conductance responses and showed an absence of the fear
      potentiated startle response during early picture processing. Both groups showed
      similar startle responses later in picture processing, and when instructed to
      "maintain" or "suppress" their emotions. BPD participants were hypo-responsive to
      aversive stimuli during early processing, and did not react with more intense
      emotional responses to affective stimuli or show a diminished ability to regulate
      their responses. These results might be consistent with the finding that
      hypersensitivity of emotional response in BPD is specific to stimuli with themes
      of particular relevance to this disorder, such as rejection and abandonment.

PMID- 29571080
TI  - Increased serum IL-36alpha and IL-36gamma levels in patients with systemic lupus
      erythematosus: Association with disease activity and arthritis.
AB  - IL-36 cytokines (IL-36Ra, IL-36alpha, IL-36beta and IL-36gamma) belong to the IL
      1 family and have been linked to several autoimmune diseases. However, little is
      known about the relationships between systemic lupus erythematosus (SLE) and IL
      36 cytokines. In this study, serum IL-36 cytokine levels were determined by
      enzyme-linked immunosorbent assay (ELISA), and their associations with SLE
      related parameters were analyzed in 72 SLE patients and 63 healthy controls.
      Additionally, IL-36 cytokine mRNA levels were assessed in 30 of 72 SLE patients
      and 20 of 63 healthy controls using real-time quantitative reverse transcription
      polymerase chain reaction (RT-PCR). Compared to healthy controls, SLE patients
      had significantly decreased serum IL-36Ra levels (P = 0.001) and markedly
      increased serum IL-36alpha and IL-36gamma levels (P = 0.004 and P = 0.001,
      respectively). Serum IL-36alpha and IL-36gamma levels were significantly higher
      in active SLE patients [SLE Disease Activity Index (SLEDAI) score >= 5] than in
      inactive patients (SLEDAI score <= 4) (P = 0.020 and P = 0.017, respectively).
      Serum IL-36alpha and IL-36gamma levels were strongly correlated with SLEDAI score
      (r = 0.308, P = 0.008 and r = 0.400, P = 0.001, respectively) and complement C3
      levels (r = -0.276, P = 0.019 and r = -0.314, P = 0.007, respectively). Moreover,
      SLE patients with arthritis had significantly higher serum IL-36alpha and IL
      36gamma levels than those without arthritis (P = 0.001 and P < 0.001,
      respectively). Our study indicates that the imbalanced antagonist/agonist profile
      of IL-36 cytokines may be linked to SLE pathogenesis. Furthermore, IL-36alpha and
      IL-36gamma may participate in arthritis and may be good biomarkers of SLE disease
      activity.

PMID- 29571081
TI  - Intramuscular and intranasal immunization with an H7N9 influenza virus-like
      particle vaccine protects mice against lethal influenza virus challenge.
AB  - The H7N9 influenza virus epidemic has been associated with a high mortality rate
      in China. Therefore, to prevent the H7N9 virus from causing further damage,
      developing a safe and effective vaccine is necessary. In this study, a vaccine
      candidate consisting of virus-like particles (VLPs) based on H7N9
      A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and
      matrix protein (M1) was successfully produced using a baculovirus (BV) expression
      system. Immunization experiments showed that strong humoral and cellular immune
      responses could be induced by the developed VLPs when administered via either the
      intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs
      administered via both immunization routes provided 100% protection against lethal
      infection caused by the H7N9 virus. The IN immunization with 40MUg of H7N9 VLPs
      induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local
      immune responses. These results provide evidence for the development of an
      effective preventive vaccine against the H7N9 virus based on VLPs administered
      through both the IM and IN immunization routes.

PMID- 29571082
TI  - Long-term survival improvement in oesophageal cancer in the Netherlands.
AB  - BACKGROUND: Treatment for oesophageal cancer has evolved due to developments
      including the centralisation of surgery and introduction of neoadjuvant
      treatment. Therefore, this study evaluated trends in stage distribution,
      treatment and survival of oesophageal cancer patients in the last 26 years in the
      Netherlands. PATIENTS AND METHODS: Patients with oesophageal cancer diagnosed in
      the period 1989-2014 were selected from the Netherlands Cancer Registry. Patients
      were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in
      stage distribution, treatment and relative survival rates were evaluated
      according to histology. RESULTS: Among all 35,760 patients, the percentage of an
      unknown tumour stage decreased from 34% to 10% during the study period, whereas
      the percentage of patients with metastatic disease increased from 21% to 34%.
      Among surgically treated patients 32% underwent a resection in a high-volume
      hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant
      chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC)
      and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000
      2004 to 43% and 26% in 2010-2014. Five-year relative survival increased from 8%
      to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to
      27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic
      patients improved from 18 to 22 weeks. CONCLUSION: In the Netherlands, survival
      for oesophageal cancer patients improved significantly, especially in the period
      2005-2014 which might be the result of better treatment related to the
      centralisation of surgery and introduction of neoadjuvant chemoradiotherapy.

PMID- 29571084
TI  - Comprehensive analysis of cancers of unknown primary for the biomarkers of
      response to immune checkpoint blockade therapy.
AB  - BACKGROUND: Cancer of unknown primary (CUP) accounts for approximately 3% of all
      malignancies. Avoiding immune destruction is a major cancer characteristic and
      therapies aimed at immune checkpoint blockade are in use for several specific
      cancer types. A comprehensive survey of predictive biomarkers to immune
      checkpoint blockade in CUP were explored in this study. METHODS: About 389 cases
      of CUP were analysed for mutations in 592 genes and 52 gene fusions using a
      massively parallel DNA sequencing platform (next-generation sequencing [NGS]).
      Total mutational load (TML) and microsatellite instability (MSI) were calculated
      from NGS data. PD-L1 expression was explored using immunohistochemistry (with 5%
      cutoff value). RESULTS: High TML was seen in 11.8% (46/389) of tumours. MSI-high
      (MSI-H) was detected in 7/384 (1.8%) of tumours. Tumour PD-L1 expression was
      detected in 80/362 CUP (22%). A small proportion of CUP cases harboured genetic
      alterations of negative predictive biomarkers to immune checkpoint inhibitors
      (predictors to hyperprogression) including MDM2 gene amplification (2%) and loss
      of function JAK2 gene mutations (1%). Amplifications of CD274 (PD-L1) and
      PDCD1LG2 (PD-L2) genes were also rare (1.4% and 0.8%, respectively). The most
      frequently mutated genes were TP53 (54%), KRAS (22%), ARID1A (13%), PIK3CA (9%),
      CDKN2A (8%), SMARCA4 (7%) and PBRM1, STK11, APC, RB1 (5%, respectively).
      CONCLUSIONS: Using a multiplex testing approach, 28% of CUP carried one or more
      predictive biomarkers (MSI-H, PD-L1 and/or TML-H) to the immune checkpoint
      blockade, providing a novel option for treatment in patients with CUP.

PMID- 29571083
TI  - Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of
      the EORTC22033-26033 clinical trial.
AB  - INTRODUCTION: The European Organisation for Research and Treatment of Cancer
      (EORTC) 22033-26033 clinical trial (NCT00182819) investigated whether initial
      temozolomide (TMZ) chemotherapy confers survival advantage compared with
      radiotherapy (RT) in low-grade glioma (LGG) patients. In this study, we performed
      gene expression profiling on tissues from this trial to identify markers
      associated with progression-free survival (PFS) and treatment response. METHODS:
      Gene expression profiling, performed on 195 samples, was used to assign tumours
      to one of six intrinsic glioma subtypes (IGSs; molecularly similar tumours as
      previously defined using unsupervised expression analysis) and to determine the
      composition of immune infiltrate. DNA copy number changes were determined using
      OncoScan arrays. RESULTS: We confirm that IGSs are prognostic in the EORTC22033
      26033 clinical trial. Specific genetic changes segregate in distinct IGSs: most
      samples assigned to IGS-9 have IDH-mutations and 1p19q codeletion, samples
      assigned to IGS-17 have IDH-mutations without 1p19q codeletion and samples
      assigned to other intrinsic subtypes often are IDH-wildtype. A trend towards
      benefit from RT was observed for samples assigned to IGS-9 (hazard ratio [HR] for
      TMZ is 1.90, P = 0.065) but not for samples assigned to IGS-17 (HR 0.87, P =
      0.62). We did not identify genes significantly associated with PFS within
      intrinsic subtypes, although follow-up time is limited. We also show that LGGs
      and glioblastomas differ in their immune infiltrate, which suggests that LGGs are
      less amenable to checkpoint inhibitor-type immune therapies. Gene expression
      analysis also allows identification of relatively rare subtypes. Indeed, one
      patient with a pilocytic astrocytoma was identified. CONCLUSION: IGSs are
      prognostic for PFS in EORTC22033-26033 clinical trial samples.

PMID- 29571085
TI  - Stability of alcohol and tobacco consumption biomarkers in a real rising main
      sewer.
AB  - Since alcohol and tobacco consumption are among the leading causes of population
      health harm, it is very important to understand the consumption behaviour to
      develop effective harm reduction strategies. Wastewater-based epidemiology (WBE)
      is a potential tool for estimating their consumption, but there are several
      uncertainties that need to be determined, including the stability of biomarkers
      in the sewer. Utilizing a real rising main sewer, this study investigated the
      stability of alcohol and tobacco consumption biomarkers. Rhodamine and acesulfame
      were used as flow tracer and benchmarker to understand the transportation of
      wastewater in the sewer with a hydraulic retention time between 2.7 and 5.0 h.
      Ethyl sulphate (EtS) and ethyl glucuronide (EtG), two biomarkers of alcohol
      consumption, were found to have different in-sewer stability, with EtS much more
      stable than EtG. The degradation rate of EtS is approximately 8% per hour, while
      EtG has a half-life of 1.9 h. Formation of nicotine, cotinine and trans-3'
      hydroxycotinine, three biomarkers for tobacco consumption, was observed during
      the experiment, probably due to deconjugation of their glucuronide chemicals. The
      deconjugation process has prevented the determination of actual stability of the
      three chemicals. However, it is suggested that cotinine is relatively stable,
      while nicotine and trans-3'-hydroxycotinine degrade to a certain degree in the
      sewer system. According to our findings, the in-sewer degradation is more
      important during the interpretation of alcohol consumption estimation than for
      tobacco consumption estimation.

PMID- 29571086
TI  - Monitoring biofilm function in new and matured full-scale slow sand filters using
      flow cytometric histogram image comparison (CHIC).
AB  - While slow sand filters (SSFs) have produced drinking water for more than a
      hundred years, understanding of their associated microbial communities is
      limited. In this study, bacteria in influent and effluent water from full-scale
      SSFs were explored using flow cytometry (FCM) with cytometric histogram image
      comparison (CHIC) analysis; and routine microbial counts for heterotrophs, total
      coliforms and Escherichia coli. To assess if FCM can monitor biofilm function,
      SSFs differing in age and sand composition were compared. FCM profiles from two
      established filters were indistinguishable. To examine biofilm in the deep sand
      bed, SSFs were monitored during a scraping event, when the top layer of sand and
      the schmutzdecke are removed to restore flow through the filter. The performance
      of an established SSF was stable: total organic carbon (TOC), pH, numbers of
      heterotrophs, coliforms, E. coli, and FCM bacterial profile were unaffected by
      scraping. However, the performance of two newly-built SSFs containing new and
      mixed sand was compromised: breakthrough of both microbial indicators and TOC
      occurred following scraping. The compromised performance of the new SSFs was
      reflected in distinct effluent bacterial communities; and, the presence of
      microbial indicators correlated to influent bacterial communities. This
      demonstrated that FCM can monitor SSF performance. Removal of the top layer of
      sand did not alter the effluent water from the established SSF, but did affect
      that of the SSFs containing new sand. This suggests that the impact of the
      surface biofilm on effluent water is greater when the deep sand bed biofilm is
      not established.

PMID- 29571087
TI  - Pinpointing wastewater and process parameters controlling the AOB to NOB activity
      ratio in sewage treatment plants.
AB  - Even though nitrification/denitrification is a robust technology to remove
      nitrogen from sewage, economic incentives drive its future replacement by
      shortcut nitrogen removal processes. The latter necessitates high potential
      activity ratios of ammonia oxidizing to nitrite oxidizing bacteria (rAOB/rNOB).
      The goal of this study was to identify which wastewater and process parameters
      can govern this in reality. Two sewage treatment plants (STP) were chosen based
      on their inverse rAOB/rNOB values (at 20  degrees C): 0.6 for Blue Plains (BP,
      Washington DC, US) and 1.6 for Nieuwveer (NV, Breda, NL). Disproportional and
      dissimilar relationships between AOB or NOB relative abundances and respective
      activities pointed towards differences in community and growth/activity limiting
      parameters. The AOB communities showed to be particularly different. Temperature
      had no discriminatory effect on the nitrifiers' activities, with similar
      Arrhenius temperature dependences (ThetaAOB = 1.10, ThetaNOB = 1.06-1.07). To
      uncouple the temperature effect from potential limitations like inorganic carbon,
      phosphorus and nitrogen, an add-on mechanistic methodology based on kinetic
      modelling was developed. Results suggest that BP's AOB activity was limited by
      the concentration of inorganic carbon (not by residual N and P), while NOB
      experienced less limitation from this. For NV, the sludge-specific nitrogen
      loading rate seemed to be the most prevalent factor limiting AOB and NOB
      activities. Altogether, this study shows that bottom-up mechanistic modelling can
      identify parameters that influence the nitrification performance. Increasing
      inorganic carbon in BP could invert its rAOB/rNOB value, facilitating its
      transition to shortcut nitrogen removal.

PMID- 29571088
TI  - Over-focused? The relation between patients' inclination for conscious control
      and single- and dual-task motor performance after stroke.
AB  - BACKGROUND: Many stroke patients are inclined to consciously control their
      movements. This is thought to negatively affect patients' motor performance, as
      it disrupts movement automaticity. However, it has also been argued that
      conscious control may sometimes benefit motor performance, depending on the task
      or patients motor or cognitive capacity. AIM: To assess whether stroke patients'
      inclination for conscious control is associated with motor performance, and
      explore whether the putative association differs as a function of task (single-
      vs dual) or patients motor and cognitive capacity. METHODS: Univariate and
      multivariate linear regression analysis were used to assess associations between
      patients' disposition to conscious control (i.e., Conscious Motor Processing
      subscale of Movement-Specific Reinvestment Scale; MSRS-CMP) and single-task
      (Timed-up-and-go test; TuG) and motor dual-task costs (TuG while tone counting;
      motor DTC%). We determined whether these associations were influenced by
      patients' walking speed (i.e., 10-m-walk test) and cognitive capacity (i.e.,
      working memory, attention, executive function). RESULTS: Seventy-eight clinical
      stroke patients (<6 months post-stroke) participated. Patients' conscious control
      inclination was not associated with single-task TuG performance. However,
      patients with a strong inclination for conscious control showed higher motor
      DTC%. These associations were irrespective of patients' motor and cognitive
      abilities. CONCLUSION: Patients' disposition for conscious control was not
      associated with single task motor performance, but was associated with higher
      motor dual task costs, regardless of patients' motor or cognitive abilities.
      CLINICAL RELEVANCE: Therapists should be aware that patients' conscious control
      inclination can influence their dual-task performance while moving. Longitudinal
      studies are required to test whether reducing patients' disposition for conscious
      control would improve dual-tasking post-stroke.

PMID- 29571089
TI  - Long-term gait outcomes following conservative management of idiopathic toe
      walking.
AB  - BACKGROUND: Idiopathic toe walking is a diagnosis of exclusion characterized by a
      persistent toe-toe gait pattern after three years of age. Treatment for toe
      walking includes physical therapy, orthotics, casting, Botulinum Toxin A
      injection into gastrocnemius/soleus muscles, and/or surgery; yet, little evidence
      exists regarding long-term treatment effects. RESEARCH QUESTION: The objective of
      this study was to explore the differences in longer-term gait outcomes and
      severity of idiopathic toe walking between children treated actively with casting
      or inactively following recommendations for stretching. METHODS: Forty-three
      adolescents and young adults (14.3-28.8 years; 21 females, 22 males) who had
      participated in an idiopathic toe walking classification study as children,
      returned for repeat physical examination and three-dimensional computerized gait
      analysis (13.4 years follow-up, range 9.4-17.8 years); 23 participants had
      received active treatment with casting and ankle foot orthotics +/- Botulinum
      Toxin A injection as children and 20 participants had received inactive treatment
      with recommended stretching exercises. Gait analysis data were compared
      retrospectively from baseline to follow-up using analysis of variance; toe
      walking severity was compared using a Wilcoxin Signed-Rank Sums test. RESULTS:
      Ankle angle at initial contact, peak dorsiflexion in stance, and toe walking
      severity improved significantly in the active treatment group only at follow-up.
      Significant improvement in peak ankle power and timing of ankle kinematics and
      kinetics in the gait cycle were found in both groups; however, greater changes
      occurred in the active treatment group. Both groups showed significantly improved
      internal plantar flexor moments, whereas knee extension increased in stance and
      passive ankle dorsiflexion decreased in both groups at follow-up (p = 0.001).
      Intermittent toe walking was reported in 49% (21/43) of participants at follow
      up. SIGNIFICANCE: The results of this study suggest that improvement in ankle
      kinematic timing and ankle kinetic gait analysis variables is sustainable,
      independent of conservative treatment for idiopathic toe walking in childhood.

PMID- 29571091
TI  - The effect of positive sagittal spine balance and reconstruction surgery on
      standing balance.
AB  - BACKGROUND: Positive sagittal spine balance (PSSB) may adversely influence
      standing balance in individuals with degenerative spine diseases. PSSB is often
      corrected with the help of spinal reconstructive surgeries involving multiple
      vertebral units. RESEARCH QUESTION: This study investigated the effect of PSSB
      and reconstructive surgery on postural sway as a measure of standing balance. The
      secondary goal of this study was to investigate the effect of reconstructive
      surgery on lower limb kinematics. METHODS: Subjects who underwent spinal
      reconstructive surgery for correction of PSSB greater than or equal to 7 cm
      participated in this study. Postural sway data while standing quietly for 20 s on
      a force platform were analyzed pre-operatively, 6-12 months and 24 months post
      operatively. RESULTS: Reconstructive surgery was successful in correcting PSSB in
      all individuals. There was a moderate correlation between PSSB and postural sway
      in the anterior-posterior (AP) direction before surgery (r = 0.58) and at 6-12
      months post-surgery (r = 0.63). Reconstructive surgery had a significant main
      effect on postural sway in both the anterior-posterior (p < 0.009, F = 7.01) and
      medial-lateral directions (p < 0, F = 12.30). Reconstructive surgery also had a
      significant main effect on standing hip (p < 0, F = 17.01) and knee flexion (p <
      0, F = 32.23). SIGNIFICANCE: These results reveal that PSSB in persons with
      degenerative spinal conditions compromised postural balance, which improved after
      reconstructive surgery. Additionally, persons with PSSB adopted a crouch posture,
      which resolved after reconstructive surgery.

PMID- 29571090
TI  - Impaired set shifting is associated with previous falls in individuals with and
      without Parkinson's disease.
AB  - BACKGROUND: Individuals with Parkinson's disease (PD) are at increased risk for
      falls, which lead to substantial morbidity and mortality. Understanding the motor
      and non-motor impairments associated with falls in PD is critical to informing
      prevention strategies. In addition to motor symptoms, individuals with PD exhibit
      non-motor deficits, including impaired set shifting, an aspect of executive
      function related to cognitive flexibility that can be measured quickly with the
      Trailmaking Test. RESEARCH QUESTION: To determine whether impaired set shifting
      is associated with fall history in people with and without PD. METHODS: We
      examined associations between set shifting, PD status, and fall history (>=1
      falls in the previous 6 months) in data from PD patients (n = 65) with and
      without freezing of gait (FOG) and community-dwelling neurologically-normal older
      adults (NON-PD) (n = 73) who had participated in our rehabilitation studies.
      RESULTS: Impaired set shifting was associated with previous falls after
      controlling for age, sex, overall cognitive function, PD status, FOG, and PD
      disease duration (OR = 1.29 [1.03-1.60]; P = 0.02). Consistent with literature,
      PD and FOG were also independently associated with increased fall prevalence (PD
      OR = 4.15 [95% CI 1.65-10.44], P < 0.01; FOG OR = 3.63 [1.22-10.80], P = 0.02).
      Although the strongest associations between set shifting and falling were
      observed among PD without FOG (OR = 2.11) compared to HOA (OR = 1.14) and PD with
      FOG (OR = 1.46), no statistically-significant differences were observed across
      groups. SIGNIFICANCE: Impaired set shifting is associated with previous falls in
      older adults with and without PD. Set shifting may be useful to include in fall
      risk assessments, particularly when global cognitive measures are within
      reference limits.

PMID- 29571092
TI  - Tm3+-doped lead silicate glass sensitized by Er3+ for efficient ~2MUm mid
      infrared laser material.
AB  - Er3+/Tm3+ co-doped lead silicate glasses with low phonon (953cm-1) and good
      thermal stability were synthesized. The ~2MUm mid-infrared emission resulting
      from the 3F4->3H6 transition of Tm3+ sensitized by Er3+ has been observed by
      808nm LD pumping. The optimal luminescence intensity was obtained in the sample
      with 1Tm2O3/2.5Er2O3 co-doped. Moreover, the energy transfer mechanism from Er3+
      to Tm3+ ion was analyzed. Absorption and emission cross section have been
      calculated. The calculated maximum emission cross section of Tm3+ is 2.689*10
      21cm2 at 1863nm. Microparameters of energy transfer between Er3+ and Tm3+ ions
      have also been analyzed. These results ensure that the prepared Er3+/Tm3+ co
      doped lead silicate glasses have excellent spectroscopic properties in mid
      infrared region and provide a beneficial guide for mid-infrared laser material.

PMID- 29571093
TI  - Spectral characterization of the fluorescent components present in humic
      substances, fulvic acid and humic acid mixed with pure benzo(a)pyrene solution.
AB  - The fate of benzo(a)pyrene (BaP), a ubiquitous contaminant reported to be
      persistent in the environment, is largely controlled by its interactions with the
      soil organic matter. In the present study, the spectral characteristics of
      fluorophores present in the physical fractions of the soil organic matter were
      investigated in the presence of pure BaP solution. After extraction of humic
      substances (HSs), and their fractionation into fluvic acid (FA) and humic acid
      (HA), two fluorescent compounds (C1 and C2) were identified and characterized in
      each physical soil fraction, by means of fluorescence excitation-emission
      matrices (FEEMs) and Parallel Factor Analysis (PARAFAC). Then, to each type of
      fraction having similar DOC content, was added an increasing volume of pure BaP
      solution in attempt to assess the behavior of BaP with the fluorophores present
      in each one. The application of FEEMs-PARAFAC method validated a three-component
      model that consisted of the two resulted fluorophores from HSs, FA and HA (C1 and
      C2) and a BaP-like fluorophore (C3). Spectral modifications were noted for
      components C2HSs (C2 in humic substances fraction) (lambdaex/lambdaem: 420/490
      520 nm), C2FA (C2 in fulvic acid fraction) (lambdaex/lambdaem: 400/487(517) nm)
      and C1HA (C1 in humic acid fraction) (lambdaex/lambdaem: 350/452(520) nm). We
      explored the impact of increasing the volume of the added pure BaP solution on
      the scores of the fluorophores present in the soil fractions. It was found that
      the scores of C2HSs, C2FA, and C1HA increased when the volume of the added pure
      BaP solution increased. Superposition of the excitation spectra of these
      fluorophores with the emission spectrum of BaP showed significant overlaps that
      might explain the observed interactions between BaP and the fluorescent compounds
      present in SOM physical fractions.

PMID- 29571094
TI  - Suppression of electron spin decoherence in Rabi oscillations induced by an
      inhomogeneous microwave field.
AB  - The decay of Rabi oscillations provides direct information about coherence of
      electron spins. When observed in EPR experiments, it is often shortened by
      spatial inhomogeneity of the microwave field amplitude in a bulk sample. In order
      to suppress this undesired loss of coherence, we propose an additional dressing
      of spin states by a weak longitudinal continuous radiofrequency field. The
      Gaussian, cosine and linear distributions of the microwave amplitude is analyzed.
      Our calculations of the Rabi oscillations between the doubly dressed spin states
      show that for all these distributions the maximum suppression of the
      inhomogeneity-induced decoherence is achieved at the so-called Rabi resonance
      when the radio-field frequency is in resonance with the Rabi frequency of spins
      in the microwave field. The manifestations of such suppression in the published
      EPR experiments with the bichromatic driving are discussed. The realization of
      the Rabi resonance using the radiofrequency field could open new possibilities
      for separating the contributions of relaxation mechanisms from those due to the
      inhomogeneous driving in spin decoherence.

PMID- 29571095
TI  - Increasing breast-cancer screening uptake: A randomized controlled experiment.
AB  - Early screening increases the likelihood of detecting cancer, thereby improving
      survival rates. National screening programs have been established in which
      eligible women receive a letter containing a voucher for a free screening. Even
      so, mammography use is often considered as remaining too low. We test four
      behavioral interventions in a large-scale randomized experiment involving 26,495
      women. Our main assumption is that, due to biases in decision-making, women may
      be sensitive to the content and presentation of the invitation letter they
      receive. None of our treatments had any significant impact on mammography use.
      Sub-sample analysis suggests that this lack of a significant impact holds also
      for women invited for the first time and low-income women.

PMID- 29571096
TI  - Sprawling and diverse: The changing U.S. population and implications for public
      lands in the 21st Century.
AB  - Public lands are typically established in recognition of their unique ecological
      value, yet both ecological and social values of public lands change over time,
      along with human distribution and land use. These transformations are evident
      even in developed countries with long histories of public land management, such
      as the United States. The 20th Century saw dramatic changes in the American
      population, in distribution and in racial and ethnic diversity, leading to new
      challenges and new roles for public lands. Our goal with this paper is to review
      changing demographics and implications for terrestrial protected areas in the
      U.S. We overview the fundamentals of population change and data, review past
      trends in population change and housing growth and their impacts on public lands,
      and then analyze the most recent decade of demographic change (2000-2010)
      relative to public lands. Discussions of demographic change and public lands
      commonly focus on the rural West, but we show that the South is also experiencing
      substantial change in rural areas with public lands, including Hispanic
      population growth. We identify those places, rural and urban, where demographic
      change (2000-2010), including diversification and housing growth, coincide with
      public lands. Understanding the current trends and long-term demographic context
      for recent changes in populations can help land managers and conservation
      scientists mitigate the effects of residential development near public lands,
      serve a more diverse population, and anticipate future population changes.

PMID- 29571097
TI  - Spatially and temporally variable urinary N loads deposited by lactating cows on
      a grazing system dairy farm.
AB  - Feed nitrogen (N) intakes in Australian grazing systems average 545 g cow-1 day
      1, indicating that urinary N is likely to be the dominant form excreted. Grazing
      animals spend disproportionate amounts of time in places on dairy farms where N
      accumulation is likely to occur. We attached to grazing cows sensors that measure
      urine volume and N concentration, as well as global positioning systems sensors
      used to monitor the times the cows spent in different places on a farm and the
      location of urination events. The cows were monitored for up to 72 h in each of
      two seasons. More urination events and greater urine volumes per event were
      recorded in spring 2014 (3.1 L) compared with winter 2015 (1.4 L), most likely
      influenced by environmental conditions and the greater spring rainfall observed.
      Mean (range) N concentration (0.71%; 0.02 to 1.52%) and N load (12.8 g cow-1
      event-1; 0.3 to 64.5 g cow-1 event-1) did not differ over the two monitoring
      periods. However, mean (range) daily N load was greater in spring (277 g cow-1
      day-1; 200 to 346 g cow-1 day-1) than in winter (90 g cow-1 day-1; 44 to 116 g
      cow-1 day-1) due to the influence of urine volume. Relatively greater time was
      spent in paddocks overnight (13.3 h) than in paddocks between morning and evening
      milking (6.4 h), compared with the mean numbers of urinations in these places
      (6.4 and 3.8 respectively). The mean N load deposited overnight in paddocks (89.6
      g cow-1) was more than twice that deposited in paddocks during the day (43.8 g
      cow-1), due to the greater N load per event overnight, and was more closely
      linked to the relative difference in time spent in paddocks than in the number of
      urination events. These data suggest that routinely holding cows in the same
      paddocks overnight will lead to high urinary N depositions, increasing the
      potential for N losses from these places. Further research using this technology
      is required to acquire farm and environment specific urinary data to improve N
      management.

PMID- 29571098
TI  - Numerical modelling of emissions of nitrogen oxides in solid fuel combustion.
AB  - Among the combustion products, nitrogen oxides are one of the main contributors
      to a negative impact on the environment, participating in harmful processes such
      as tropospheric ozone and acid rains production. The main source of emissions of
      nitrogen oxides is the human combustion of fossil fuels. Their formation models
      are investigated and implemented with the goal of obtaining a tool for studying
      the nitrogen-containing pollutant production. In this work, numerical simulation
      of solid fuel combustion was carried out on a three-dimensional model of a drop
      tube furnace by using the commercial software FIRE. It was used for simulating
      turbulent fluid flow and temperature field, concentrations of the reactants and
      products, as well as the fluid-particles interaction by numerically solving the
      integro-differential equations describing these processes. Chemical reactions
      mechanisms for the formation of nitrogen oxides were implemented by the user
      functions. To achieve reasonable calculation times for running the simulations,
      as well as efficient coupling with the turbulent mixing process, the nitrogen
      scheme is limited to sufficiently few homogeneous reactions and species.
      Turbulent fluctuations that affect the reaction rates of nitrogen oxides'
      concentration are modelled by probability density function approach. Results of
      the implemented model for nitrogen oxides' formation from coal and biomass are
      compared to the experimental data. Temperature, burnout and nitrogen oxides'
      concentration profiles are compared, showing satisfactory agreement. The new
      model allows the simulation of pollutant formation in the real-world
      applications.

PMID- 29571099
TI  - Application of ATAD technology for digesting sewage sludge in small towns:
      Operation and costs.
AB  - In an economic context marked by increasing energy costs and stricter legislation
      regarding the landfill disposal of wastewater treatment plant (WWTP) sewage
      sludge, and where biomethanization is difficult to implement in small WWTPs, an
      efficient alternative is required to manage this polluting waste. This study
      shows that autothermal thermophilic aerobic digestion (ATAD) is a feasible
      technique for treating sewage sludge in small- and medium-sized towns. The
      experiments were carried out at pilot scale on a cyclical basis and in continuous
      mode for nine months. The main results showed an optimal hydraulic retention time
      of 7 days, which led to an organic matter removal of 34%. The sanitized sludge
      meets the microbial quality standards for agronomic application set out in the
      proposed European sewage sludge directive. An economic assessment for the
      operation of ATAD technology was carried out, showing a treatment cost of
      ?6.5/ton for dewatered sludge.

PMID- 29571100
TI  - Distribution and sources of particulate mercury and other trace elements in PM2.5
      and PM10 atop Mount Tai, China.
AB  - The concentrations of particulate mercury (PHg) and other trace elements in PM2.5
      and PM10 in the atmosphere were measured at the summit of Mount Tai during the
      time period of 15 June - 11 August 2015. The average PHg concentrations were
      83.33 +/- 119.1 pg/m3 for PM2.5 and 174.92 +/- 210.5 pg/m3 for PM10. Average
      concentrations for other trace elements, including Al, Ca, Fe, K, Mg, Na, Pb, As,
      Se, Cu, Cd, Cr, V, Mo, Co, Ag, Ba, Mn, Zn and Ni ranged from 0.06 ng/m3 (Ag) to
      354.33 ng/m3 (Ca) in PM2.5 and 0.11 ng/m3 (Co) to 592.66 ng/m3 (Ca) in PM10. The
      average concentrations of PHg were higher than those at other domestic mountain
      sites and cities in other counties, lower than those at domestic city sites.
      Other trace elements showed concentrations lower than those at the domestic
      mountain sites. Due possibly to increased control of emissions and the proportion
      of new energy, the PHg and trace element concentrations decreased, but the PHg
      showed concentrations higher than those at the Mountain sites, this showed that
      the reasons was not only severely affected by anthropogenic emissions, but also
      associated with other sources. The concentration changed trend of the main trace
      elements indicated that PHg, trace elements and particle matters present positive
      correlation and fine particulate matter has a greater surface area which was
      conductive to adsorption of Hg and trace elements to particles. On June 19, June
      27 and July 6, according to the peak of mercury and trace elements, we can
      predict the potential sources of these three days. The results of principal
      component analysis (PCA) suggested that, crustal dust, coal combustion, and
      vehicle emissions were the main emission sources of PHg and other trace elements
      in Mount Tai. The 24-h backward trajectories and potential source contribution
      function (PSCF) analysis revealed that air masses arriving at Mount Tai were
      mainly affected by Shandong province. Mount Tai was subjected to five main
      airflow trajectories. Clusters 1, 2, 3, and 5 represented four pathways for local
      and regional sources and cluster 4 originated long-distance transportation.
      Central Shandong was the main source regions of PHg, Pb, Se, As, Cu and Cd.
      Southeastern and northwestern Shandong province and northern Jiangsu province
      were the most polluted source regions of Mn, Zn, and Ni. The crustal elements Fe
      and Ca had similar distributions of potential source regions, suggested by the
      highest PSCF values in southeastern Shandong and northern Jiangsu.

PMID- 29571101
TI  - Importance of hydrophobic interactions in the single-chained cationic surfactant
      DNA complexation.
AB  - The goal of this work was to understand the key factors determining the DNA
      compacting capacity of single-chained cationic surfactants. Fluorescence, zeta
      potential, circular dichroism, gel electrophoresis and AFM measurements were
      carried out in order to study the condensation of the nucleic acid resulting from
      the formation of the surfactant-DNA complexes. The apparent equilibrium binding
      constant of the surfactants to the nucleic acid, Kapp, estimated from the
      experimental results obtained in the ethidium bromide competitive binding
      experiments, can be considered directly related to the ability of a given
      surfactant as a DNA compacting agent. The plot of ln(Kapp) vs. ln(cmc), cmc being
      the critical micelle concentration, for all the bromide and chloride surfactants
      studied, was found to be a reasonably good linear correlation. This result shows
      that hydrophobic interactions mainly control the surfactant DNA compaction
      efficiency.

PMID- 29571102
TI  - Role of CuO in improving NH3 and SO2 capture on nanoporous Fe2O3 sorbents.
AB  - In this work, mixed Fe/Cu oxides as sorbents for SO2 and NH3 removal were
      investigated. Nanoporous iron oxide mixed with 10, 20 and 30 at.% CuO were
      prepared by thermal decomposition of the corresponding oxalates at 250  degrees C
      for 5 h in air. The mixed Fe/Cu oxalates were obtained from the co-precipitation
      of iron/copper sulfate and ammonium oxalate during ultrasonication. The physical
      properties of the oxalate precursors and the resulting mixed Fe/Cu oxides were
      characterized with SEM, TGA-DSC, FTIR, powder XRD and Mossbauer spectroscopy. The
      porosity was studied by N2 adsorption-desorption isotherms and small angle X-ray
      scattering. Evenly dispersed CuO hindered the crystallization of Fe2O3, which
      significantly increased the specific BET surface area from 211 m2/g for Fe2O3 to
      354 m2/g for Fe0.8Cu0.2Ox. As a result, SO2 and NH3 adsorption on Fe0.8Cu0.2Ox
      were enhanced by about 70% compared to Fe2O3. Compared to Fe2O3-impregnated
      activated carbons, nanoporous Fe0.8Cu0.2Ox could capture five times more SO2 per
      unit weight, which will be attractive for applications in respirators with lower
      weight and smaller size.

PMID- 29571103
TI  - TiO2 nanocrystals decorated Z-schemed core-shell CdS-CdO nanorod arrays as high
      efficiency anodes for photoelectrochemical hydrogen generation.
AB  - TiO2 nanocrystals decorated core-shell CdS-CdO nanorod arrays, TiO2@CdO/CdS NR,
      were fabricated as high efficiency anodes for photoelctrochemical hydrogen
      generation. The novel sandwich heterostructure was constructed from first growth
      of CdS nanorod arrays on a fluorine doped tin oxide (FTO) substrate with a
      hydrothermal process, followed by in situ generation of CdO thin films of single
      digit nanometers from the CdS nanorod surfaces through thermal oxidation, and
      final decoration of TiO2 nanocrystals of 10-20 nm via a successive ionic layer
      absorption and reaction process. The core-shell CdS-CdO heterostructure possesses
      a Z-scheme band structure to enhance interfacial charge transfer, facilitating
      effective charge separation to suppress electron-hole recombination within CdS
      for much improved current density generation. The final decoration of TiO2
      nanocrystals passivates surface defects and trap states of CdO, further
      suppressing surface charge recombination for even higher photovoltaic conversion
      efficiencies. The photoelectrochemical performances of the plain CdS nanorod
      array were significantly improved with the formation of the sandwich
      heterostructure, achieving a photo current density of 3.2 mA/cm2 at 1.23 V (vs.
      RHE), a 141% improvement over the plain CdS nanorod array and a 32% improvement
      over the CdO/CdS nanorod array.

PMID- 29571104
TI  - Saturated imbibition under the influence of gravity and geometry.
AB  - HYPOTHESIS: The effect of gravity was generally neglected in the classical
      imbibition law for one dimensional geometries. Following researches complemented
      the classical "Lucas-Washburn law" with consideration of gravity, but no
      examination of geometries under influence of gravity has been done, while
      geometry was shown to yield different scaling law for the imbibition process.
      Hence, it is possible to discover new time exponents for imbibition length in two
      dimensional and three dimensional imbibition process under gravity. METHODS:
      Through theoretical analysis and numerical simulations, the size of wetted region
      under three gravitational scenarios (zero gravity, acceleration and deceleration)
      in three geometries (one dimensional, two dimensional radial and three
      dimensional radial) are determined quantitatively. FINDINGS: New time exponents
      other than classic 1/2 are identified under different directions of gravity in
      two dimensional radial and three dimensional radial imbibition, and symmetry of
      time exponents due to different directions of gravity is discovered. A new time
      exponent of 1 for the acceleration case in one dimensional imbibition is found.
      The flow field in the wetted region is also determined from simulations.
      Discoveries in this paper show that new physical laws for imbibition length exist
      at the intersection of gravity and geometry.

PMID- 29571105
TI  - Superparamagnetic silica core-shell hybrid attached to graphene oxide as a
      promising recoverable catalyst for expeditious synthesis of TMS-protected
      cyanohydrins.
AB  - Fe3O4/SiO2 core-shell hybrid nanoparticles covalently attached to graphene oxide
      (Fe3O4/SiO2/PTS-GO) were prepared and fully characterized using different
      techniques including Fourier transform infrared (FTIR) spectroscopy, X-ray powder
      diffraction (XRD), field emission scanning electron microscopy (FESEM), energy
      dispersive X-ray (EDX) spectroscopy, transmission electron microscopy (TEM) and
      atomic force microscopy (AFM). The efficiency of Fe3O4/SiO2/PTS-GO nanocomposite
      was demonstrated in trimethylsilyl cyanide (TMSCN) addition to a wide range of
      aldehydes and ketones in high to quantitative yields under extremely mild
      conditions. Low catalyst loading, reusability of the catalyst, avoiding the use
      of any hazardous solvent, short reaction time at ambient temperature and
      straightforward work up procedure are some of the attractive advantages of this
      protocol.

PMID- 29571106
TI  - Transition support for new graduate and novice nurses in critical care settings:
      An integrative review of the literature.
AB  - Transition into critical care areas for new graduate nurses may be more difficult
      than transitioning into other areas due to the specialised knowledge needed. It
      is unknown which aspects of transition programs best support new graduate nurses
      improve competence and confidence to transition into critical care nursing
      specialties. Identifying these aspects would assist to design and implement best
      practice transition programs for new graduates in critical care areas. Themes
      identified in the literature include; having a designated resource person,
      workplace culture, socialisation, knowledge and skill acquisition, orientation,
      and rotation. Allocation of a quality resource person/s, supportive workplace
      culture, positive socialisation experiences, knowledge and skill acquisition and
      structured orientation based on new graduates' learning needs all positively
      supported increased confidence, competence and transition into nursing practice.
      Rotations between areas within graduate programs can potentially have both
      positive and negative impacts on the transition process. Negative impacts of
      including a rotation component in a transition program should be carefully
      considered alongside perceived benefits when designing new graduate nurse
      transition programs.

PMID- 29571107
TI  - Adsorption behavior of Ni(II) onto activated carbons from hide waste and high
      pressure steaming hide waste.
AB  - This work reports the preparation and adsorption of Ni(II) via activated carbons
      which produced from hide waste (HWAC) and high-pressure steaming hide waste
      (HWSAC) with potassium silicate as the activating agent. The best preparation
      condition for HWAC and HWSAC was the activation temperature of 700  degrees C
      using an impregnation ratio of 2:1. Both of them were characterized by N2
      adsorption/desorption isotherms, SEM and FT-IR spectra. The surface area of HWAC
      and HWSAC was 1804.37 and 1361.26 m2/g, respectively. Despite the surface area of
      HWAC being larger than that of HWSAC, but the adsorption capacity of Ni(II) for
      HWAC was lower than that for HWSAC. Furthermore, the adsorption capacity of
      Ni(II) for both HWAC and HWSAC showed pH-dependent behavior and increased with
      the increase in pH value, which can be attributed to the functional groups of
      HWAC and HWSAC materials through the electrostatic attraction. The adsorption
      data for HWAC and HWSAC were fitted with four isotherm models (Langmuir,
      Freundlich, Temkin, and Dubinin-Radushkevich) and four kinetic models (pseudo
      first order model, pseudo-second order model, intra-particle diffusion and
      Elovich equation), indicating that Langmuir isotherm and Pseudo-second order
      model fitted well with high coefficient of determination (R2 > 0.99) for both the
      two adsorbents. The positive enthalpy of adsorption (DeltaH) and free energy of
      adsorption (DeltaG) indicate a spontaneous and endothermic nature of the process.
      These results demonstrated that activated carbon can be prepared from hide waste
      which could remove heavy metal such as Ni(II) effectively.

PMID- 29571108
TI  - Effects of dietary Pb and Cd and their combination on lysosomal and tissue-level
      biomarkers and histopathology in digestive gland of the land snail, Cantareus
      apertus (Born, 1778).
AB  - The present study was aimed at determining cell and tissue-level biomarkers and
      histopathological alterations in the green garden snail, Cantareus apertus (Born,
      1778), exposed to different nominal dietary concentrations of Pb (25, 100 and
      2500 mg Pb/kg), Cd (5, 10 and 100 mg Cd/kg) and their combination (25 mg Pb + 5
      mg Cd/Kg, 100 mg Pb + 10 mg Cd/kg and 2500 mg Pb + 100 mg Cd/ kg) for 1 and 8
      weeks. Lead and Cd exerted histopathological effects on the digestive gland in a
      dose-dependent manner and related to lysosomal and tissue-level biomarkers. The
      biological responses observed included digestive cell vacuolisation and numerical
      atrophy, calcium cell hydropic degeneration, excretory cell hypertrophy,
      inflammatory responses, blood vessel congestion, and disruption of the blood
      vessel wall and the interstitial connective tissue. Lysosomal enlargement and
      transient intracellular accumulation of neutral lipids and lipofuscins were also
      observed, together with alterations in the cell type composition and thinning of
      the digestive gland epithelium and with diverticular distortion. This response
      profile fits well with the biological effects reported after metal exposure in
      gastropods from other regions, as well as with data obtained in parallel studies
      dealing with metal bioaccumulation and intralysosomal accumulation, mortality,
      feeding, growth, oxidative stress and neurotoxicity exerted elicited by Pb, Cd
      and their mixture in green garden snails under the present experimental
      conditions. Consequently, C. apertus seems to be a suitable model species for the
      biomarker-based assessment of the biological effects of Pb and Cd, alone or in
      combinations, thus providing a challenging opportunity to advance in identifying
      suitable sentinel species for metal pollution biomonitoring and ecosystem health
      assessment in soil ecosystems in Northern Africa.

PMID- 29571109
TI  - Yucca schidigera extract modulates the lead-induced oxidative damage, nephropathy
      and altered inflammatory response and glucose homeostasis in Japanese quails.
AB  - The present study was conducted to explore the toxic effects of lead (Pb) on the
      physiological responses of Japanese quails and to investigate the potential
      modulatory role of Yucca schidigera extract (YSE) against these effects. 360
      mature Japanese quails (at 2 months of age) were used and the experiment was
      lasted for 8 weeks. The birds were divided into six equal groups as follow:
      control (basal diet, BD), BD+Pb (100 mg/kg diet), BD+YSE (100 mg/kg diet), BD+YSE
      (200 mg/kg diet), BD+Pb (100 mg/kg diet) +YSE (100 mg/kg diet) and BD+ Pb (100
      mg/kg diet) + YSE (200 mg/kg diet). Pb induced a significant reduction in
      superoxide dismutase (SOD) and catalase (CAT) activities and reduced glutathione
      (GSH) level. While, increased protein carbonyl (PC) and malondialdehyde (MDA)
      content in tissues of exposed birds. Pb increased level of 8-hydroxy-2
      deoxyguanosine (8-OHdG) and lactate dehydrogenase (LDH) activity in serum. YSE
      significantly reduced the Pb -induced oxidative stress in co-treated groups
      especially at 200 mg/kg diet. YSE could modulate the Pb -induced decreased urea,
      creatinine and beta-2 microglobulin (B2M) levels. YSE200 was found to be better
      than the YSE100 in decreasing levels of inflammatory markers including tumor
      necrosis factor (TNF-alpha), nitric oxide (NO), transforming growth factor-beta1
      (TGF-beta1) and vascular endothelial growth factor (VEGF). Furthermore, YSE
      significantly regulates glucose homeostasis in co-exposed quails. Pb residues
      were found to be significantly higher in kidney and pancreas tissues of Pb group
      compared to other groups. YES decreased the expression of metallothionein-1 in
      the renal and pancreatic tissues, while elevated insulin expression in the
      pancreatic cells by immunostaining in co-exposed groups. In conclusion, the
      present results conclusively demonstrate the potential modulatory effect of YSE
      against the Pb-induced toxic effects in different organs of Japanese quails.

PMID- 29571110
TI  - Spatial variation of polycyclic aromatic hydrocarbons (PAHs) in surface sediments
      from rivers in hilly regions of Southern China in the wet and dry seasons.
AB  - Seasonal variations of polycyclic aromatic hydrocarbons (PAHs) in the surface
      sediments from 13 rivers in hilly regions of southern China were studied.
      Concentrations of PAHs analyzed in the wet season were higher than those analyzed
      in the dry season, with residues ranging from 74.3 to 1930.9 ng g-1 dw in the wet
      season and from 96.9 to 1388.9 ng g-1 dw in the dry season. The primary
      contributors were 3- and 4-ringed congeners accounting for 59.8% +/- 10.1% and
      58.3% +/- 9.3% of the identified PAHs in the wet and the dry seasons,
      respectively. Proximity to sources and locations susceptible to high atmospheric
      depositional inputs results in high concentrations of PAH. Diagnostic ratios have
      indicated that the sources of PAHs in different seasons make no apparent
      difference. Furthermore, a principal component analysis and multiple linear
      regression (PCA-MLR) studies indicate that combustion sources such as vehicle
      emissions and coal combustion are the primary sources of PAHs. Toxicological risk
      assessments based on TEQcare suggested that Benzo[a]pyrene, benz[a]anthracene,
      dibenz[a,h]anthracene could pose high ecological risks in this area.

PMID- 29571111
TI  - Spatial patterns of pharmaceuticals and wastewater tracers in the Hudson River
      Estuary.
AB  - The widespread use of pharmaceuticals by human populations results in their
      sustained discharge to surface waters via wastewater treatment plants (WWTPs). In
      this study, 16 highly prescribed pharmaceuticals were quantified along a 250 km
      transect of the Hudson River Estuary and New York Harbor to describe their
      sources and spatial patterns. Sampling was conducted over two dry weather periods
      in May and July 2016, at 72 sites which included mid-channel and nearshore sites,
      as well as locations influenced by tributaries and WWTP outfalls. The detection
      frequency of the study pharmaceuticals was almost identical between the May and
      July sampling periods at 55% and 52%, respectively. Six pharmaceuticals were
      measurable at 92% or more of the sites during both sampling periods, illustrating
      their ubiquitous presence throughout the study area. Individual pharmaceutical
      concentrations were highly variable spatially, ranging from non-detect to 3810
      ng/L during the study. Major factors controlling concentrations were proximity
      and magnitude of WWTP discharges, inputs from tributaries and tidal mixing. Two
      compounds, sucralose and caffeine, were evaluated as tracers to identify
      wastewater sources and assess pharmaceutical behavior. Sucralose was useful in
      identifying wastewater inputs to the river and concentrations showed excellent
      correlations with numerous pharmaceuticals in the study. Caffeine-sucralose
      ratios showed potential in identifying discharges of untreated wastewater
      occurring during a combined sewage overflow event. Many of the study
      pharmaceuticals were present throughout the Hudson River Estuary as a consequence
      of sustained wastewater discharge. Whereas some concentrations were above
      published effects levels, a more complete risk assessment is needed to understand
      the potential for ecological impacts due to pharmaceuticals in the Hudson River
      Estuary.

PMID- 29571112
TI  - Composition, sources, and bioavailability of nitrogen in a longitudinal gradient
      from freshwater to estuarine waters.
AB  - Nitrogen (N) transport from land to water is a dominant contributor of N in
      estuarine waters leading to eutrophication, harmful algal blooms, and hypoxia.
      Our objectives were to (1) investigate the composition of inorganic and organic N
      forms, (2) distinguish the sources and biogeochemical mechanisms of nitrate-N
      (NO3-N) transport using stable isotopes of NO3- and Bayesian mixing model, and
      (3) determine the dissolved organic N (DON) bioavailability using bioassays in a
      longitudinal gradient from freshwater to estuarine ecosystem located in the Tampa
      Bay, Florida, United States. We found that DON was the most dominant N form
      (mean: 64%, range: 46-83%) followed by particulate organic N (PON, mean: 22%,
      range: 14-37%), whereas inorganic N forms (NOx-N: 7%, NH4-N: 7%) were 14% of
      total N in freshwater and estuarine waters. Stable isotope data of NO3- revealed
      that nitrification was the main contributor (36.4%), followed by soil and organic
      N sources (25.5%), NO3- fertilizers (22.4%), and NH4+ fertilizers (15.7%).
      Bioassays showed that 14 to 65% of DON concentrations decreased after 5-days of
      incubation indicating utilization of DON by microbes in freshwater and estuarine
      waters. These results suggest that despite low proportion of inorganic N forms,
      the higher concentrations and bioavailability of DON can be a potential source of
      N for algae and bacteria leading to water quality degradation in the estuarine
      waters.

PMID- 29571113
TI  - Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and
      EGFR receptor inhibitors.
AB  - A new series of benzimidazole linked pyrazole derivatives were synthesized by
      cyclocondensation reaction through one-pot multicomponent reaction in absolute
      ethanol. All the synthesized compounds were tested for their in vitro anticancer
      activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231,
      A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the
      compounds. Majority of the compounds showed potent antiproliferative activity
      against the tested cancer cell lines. Compound 5a showed the most effective
      activity against the lungs cancer cell lines (IC50 = 2.2 uM) and EGFR binding
      (IC50 = 0.97 uM) affinity as compared to other members of the series. Compound 5a
      inhibited growth of A549 cancer cells by inducing a strong G2/M phase arrest. In
      addition, same compound inhibited growth of A549 cancer cells by inducing
      apoptosis. In molecular docking studies compound 5a was bound to the active
      pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two pi-pi
      interaction with binding energies DeltaG = -34.581 Kcal/mol.

PMID- 29571114
TI  - Mechanically strong dual responsive nanocomposite double network hydrogel for
      controlled drug release of asprin.
AB  - Mechanically strong dual/multi-stimuli-responsive smart hydrogels have attracted
      extensive attention in recent years. A novel tough, mechanical strong and
      biocompatible dual pH- and temperature- responsive poly (N-isopropylacrylamide)
      /clay (laponite XLG)/carboxymethyl chitosan (CMCTs) /genipin nanocomposite double
      network hydrogel was synthesized through a facile, one-pot free radical
      polymerization initiated by the ultraviolet light, using clay and the natural
      molecular-genipin as the cross-linkers instead of toxic organic molecules.
      Crucial factors, the content of CMCTs, clay and genipin, for synthesizing the
      mechanical strong hydrogels were investigated. When the content of CMCTs, clay
      and genipin were 5 wt%, 33.3 wt% and 0.175 wt%, respectively (to the weight of N
      isopropylacrylamide), these prepared hydrogels exhibited a high tensile strength
      of 137.9 kPa at the failure strain of 446.1%. Furthermore, the relationship
      between swelling and deswelling rate of the synthesized hydrogels and the above
      crucial factors were also studied. Besides, the synthesized hydrogels displayed a
      considerable controlled release property of asprin by tuning their inner
      crosslink density. Owing to this property, they may have great potential in the
      drug delivery systems.

PMID- 29571115
TI  - Compressive fatigue properties of commercially available standard and low-modulus
      acrylic bone cements intended for vertebroplasty.
AB  - Vertebroplasty (VP) is a minimally invasive surgical procedure commonly used to
      relieve severe back pain associated with vertebral compression fractures. The
      poly(methyl methacrylate) bone cement used during this procedure is however
      presumed to facilitate the occurrence of additional fractures next to the treated
      vertebrae. A reason for this is believed to be the difference in stiffness
      between the bone cement and the surrounding trabecular bone. The use of bone
      cements with lower mechanical properties could therefore reduce the risk of
      complications post-surgery. While intensive research has been performed on the
      quasi-static mechanical properties of these cements, there is no data on their
      long-term mechanical properties. In the present study, the in vitro compressive
      fatigue performance as well as quasi-static mechanical properties of two
      commercially available acrylic bone cements - a low-modulus cement
      (Resilience(r)) and a standard cement (F20) from the same manufacturer - were
      determined. The quasi-static mechanical properties of the low-modulus and
      standard cements after 24 h of setting were in the range of other vertebroplastic
      cements (sigma = 70-75 MPa; E= 1600-1900 MPa). F20 displayed similar mechanical
      properties over time in 37  degrees C phosphate buffered saline solution, while
      the mechanical properties of the Resilience(r) cement decreased gradually due to
      an increased porosity in the polymeric matrix. The standard cement exhibited a
      fatigue limit of approx. 47 MPa, whereas the low-modulus cement showed a fatigue
      limit of approx. 31 MPa. In summary, the low-modulus bone cement had a lower
      fatigue limit than the standard cement, as expected. However, this fatigue limit
      is still substantially higher than the stresses experienced by vertebral
      trabecular bone.

PMID- 29571116
TI  - The critically ill patient with tuberculosis in intensive care: Clinical
      presentations, management and infection control.
AB  - Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2016, there
      were 490,000 cases of multi-drug resistant TB globally. Over 2 billion people
      have asymptomatic latent Mycobacterium tuberculosis infection. TB represents an
      important, but neglected management issue in patients presenting to intensive
      care units. Tuberculosis in intensive care settings may present as the primary
      diagnosis (active drug sensitive or resistant TB disease). In other patients TB
      may be an incidental co-morbid finding as previously undiagnosed sub-clinical or
      latent TB which may re-activate under conditions of stress and immunosuppression.
      In Sub-Saharan Africa, where co-infection with the human immunodeficiency virus
      and other communicable diseases is highly prevalent, TB is one of the most
      frequent clinical management issues in all healthcare settings. Acute respiratory
      failure, septic shock and multi-organ dysfunction are the most common reasons for
      intensive care unit admission of patients with pulmonary or extrapulmonary TB.
      Poor absorption of anti-TB drugs occurs in critically ill patients and worsens
      survival. The mortality of patients requiring intensive care is high. The
      majority of early TB deaths result from acute cardiorespiratory failure or septic
      shock. Important clinical presentations, management and infection control issues
      regarding TB in intensive care settings are reviewed.

PMID- 29571117
TI  - Fabric phase sorptive extraction-high performance liquid chromatography-photo
      diode array detection method for simultaneous monitoring of three inflammatory
      bowel disease treatment drugs in whole blood, plasma and urine.
AB  - This paper reports a novel fabric phase sorptive extraction-high performance
      liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the
      simultaneous extraction and analysis of three drug residues (ciprofloxacin,
      sulfasalazine, and cortisone) in human whole blood, plasma, and urine samples,
      generally administered in human patients to treat inflammatory bowel disease
      (IBD). The drugs of interest were well resolved using a Luna C18 column (250 mm *
      4.6 mm; 5 MUm particle size) in gradient elution mode within 20 min. The
      analytical method was optimized and validated in the range 0.05-10 MUg/mL for
      whole blood, 0.25-10 MUg/mL for human plasma, and 0.10-10 MUg/mL for human urine.
      Blank human whole blood, plasma, and urine were used as the sample matrix for the
      method development and validation; while methyl-p-hydroxybenzoate was used as the
      internal standard (IS). Weighted-matrix matched standard calibration curves
      showed a good linearity up to a concentration of 10 MUg/mL. The intra- and inter
      day accuracy values (precision and trueness) were found in the range from -10.9%
      to 12.3%, and the performances of the validated FPSE-HPLC-PDA were further tested
      on real IBD patient samples. This is the first FPSE procedure applied
      simultaneously to whole blood, plasma, and urine samples for the determination of
      residual IBD drugs, which possess a wide range of polarity (logP values ranging
      from 2.30 for Ciprofloxacin, to 1.66 for Cortisone, and 2.92 for Sulfasalazine).
      The new approach exhibits high potential for immediate adoptation as a rapid,
      robust and green analytical tool for future clinical and pharmaceutical
      applications.

PMID- 29571118
TI  - Analysis of 10 beta-agonists in pork meat using automated dispersive pipette
      extraction and LC-MS/MS.
AB  - An analytical procedure for the analysis of 10 beta-adrenergic agonists
      (cimaterol, terbutaline, salbutamol, isoxsuprine, ractopamine, cimbuterol,
      clenbuterol, brombuterol, mabuterol and mapenterol) in pork meat was developed
      and validated using LC-MS/MS. An automated dispersive pipette extraction (DPX)
      was employed on a Hamilton Microlab(r) NIMBUS96(r) platform to extract the
      analytes of interest prior to LC-MS/MS analysis. The extraction time was <20 min
      with a total LC-MS/MS run time of 9.6 min. The method was fully validated in
      accordance with the international guidelines (European Commission Decision
      2002/657/EC and National Standards of People's Republic of China, GB/T 22286
      2008) for limit of detection, limit of quantitation, carryover, extraction
      efficiency, matrix effects, linearity, and within and between-run precision. The
      proposed method can be successfully used in the routine determination of 10 beta
      adrenergic agonists in pork and as a potential solution for compliance monitoring
      in regulatory laboratories.

PMID- 29571119
TI  - Improved phosphometabolome profiling applying isotope dilution strategy and
      capillary ion chromatography-tandem mass spectrometry.
AB  - The phosphometabolome is comprised of all phosphorylated metabolites including
      the major metabolite classes sugar phosphates and nucleoside phosphates.
      Phosphometabolites are invaluable in any cell as a part of primary- and energy-
      metabolism, and as building blocks in the biosynthesis of macromolecules. Here,
      we report quantitative profiling of the phosphometabolome by applying capillary
      ion chromatography-tandem mass spectrometry (capIC-MS/MS), ensuring improved
      chromatographic separation, robustness and quantitative precision. Baseline
      separation was achieved for six out of eight tested hexose phosphates.
      Quantitative precision and reproducibility was improved by introducing a fully
      uniformly (U) 13C-labeled biological extract and applying an isotope dilution
      (ID) correction strategy. A 13C-labeled biological extract does in principle
      contain internal standards (IS) for all metabolites, but low abundant metabolites
      pose a challenge, and solutions to this are discussed. The extreme
      reproducibility and reliability of this capIC-MS/MS method was demonstrated by
      running the instrumentation continuously for ten days.

PMID- 29571120
TI  - Emotion identification and aging: Behavioral and neural age-related changes.
AB  - OBJECTIVE: Aging is known to alter the processing of facial expressions of
      emotion (FEE), however the impact of this alteration is less clear. Additionally,
      there is little information about the temporal dynamics of the neural processing
      of facial affect. METHODS: We examined behavioral and neural age-related changes
      in the identification of FEE using event-related potentials. Furthermore, we
      analyze the relationship between behavioral/neural responses and
      neuropsychological functioning. To this purpose, 30 younger adults, 29 middle
      aged adults and 26 older adults identified FEE. RESULTS: The behavioral results
      showed a similar performance between groups. The neural results showed no
      significant differences between groups for the P100 component and an increased
      N170 amplitude in the older group. Furthermore, a pattern of asymmetric
      activation was evident in the N170 component. Results also suggest deficits in
      facial feature decoding abilities, reflected by a reduced N250 amplitude in older
      adults. Neuropsychological functioning predicts P100 modulation, but does not
      seem to influence emotion identification ability. CONCLUSIONS: The findings
      suggest the existence of a compensatory function that would explain the age
      equivalent performance in emotion identification. SIGNIFICANCE: The study may
      help future research addressing behavioral and neural processes involved on
      processing of FEE in neurodegenerative conditions.

PMID- 29571121
TI  - Prediction of secondary generalization from a focal onset seizure in
      intracerebral EEG.
AB  - OBJECTIVE: We propose a system based on the first five seconds of intracerebrally
      recorded focal seizures to predict their evolution from focal to bilateral tonic
      clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic
      component (FS), or to a seizure remaining focal (F). METHODS: Nineteen time and
      frequency domain features were extracted from 39 seizures of 32 patients and were
      subjected to support vector machine based classification. Three prediction
      approaches regarding seizure evolution were (1) FTC vs FS vs F, (2) FTC vs FS or
      F and (3) FTC or FS vs F. RESULTS: We used 21 seizures for training. Most
      features had significantly different distributions in the three seizure types (p
      < 0.05). Eighteen seizures were used for testing. We predicted the evolution of
      12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in
      FTC or FS vs F. CONCLUSION: The first five seconds of a focal seizure contains
      information regarding the eventual evolution of the seizure, which could be
      predicted in most seizures. SIGNIFICANCE: The proposed system could alert the
      health care team when a patient is hospitalized for intracerebral EEG and improve
      safety and eventually result in an implantable device.

PMID- 29571122
TI  - Connectivity inference from neural recording data: Challenges, mathematical bases
      and research directions.
AB  - This article presents a review of computational methods for connectivity
      inference from neural activity data derived from multi-electrode recordings or
      fluorescence imaging. We first identify biophysical and technical challenges in
      connectivity inference along the data processing pipeline. We then review
      connectivity inference methods based on two major mathematical foundations,
      namely, descriptive model-free approaches and generative model-based approaches.
      We investigate representative studies in both categories and clarify which
      challenges have been addressed by which method. We further identify critical open
      issues and possible research directions.

PMID- 29571123
TI  - Implementation of the RCOG guidelines for prevention of obstetric anal sphincter
      injuries (OASIS) at two London Hospitals: A time series analysis.
AB  - OBJECTIVE: To audit the impact of implementation of the RCOG guidelines for
      prevention of Obstetric anal sphincter injuries (OASIS) by introducing antenatal
      perineal massage, manual perineal protection, and cutting episiotomies at 60
      degrees  to the midline at the time of crowning. DESIGN: Time series analysis;
      Setting - Two London teaching hospitals; Royal Free London (RFL) and Barnet;
      Population or Sample - All nulliparous women undergoing vaginal birth; Methods -
      Training was provided for above techniques. EPISCISSORS-60 were introduced to
      perform 60 degrees  episiotomies. Data were extracted from maternity databases
      and dashboards; Main Outcome Measures - OASIS rates before and after
      implementation. RESULTS: Data from 2566 births were analysed. In operative
      vaginal deliveries (OVD), OASIS declined from 9.6% to 2% (p = 0.001) at Barnet
      and from 5.6% to 4.2% (p = 0.4) at RFL. OASIS reduced in nulliparous OVD's given
      episiotomies from 6.3% in the 'before' period to 0.6% in the 'after' period [p =
      0.01] at Barnet. Before introduction of the EPISCISSORS-60, OASIS rate was 6.3%
      with episiotomies and 30% without episiotomies (p = 0.000). After introduction of
      the EPISCISSORS-60, OASIS rate was 0.63% with episiotomies v 16% without
      episiotomies (p = 0.000) at Barnet. At RFL, OASIS rate was 2.6% with
      episiotomies, and 42% without episiotomy (p = 0.000). In SVD's at Barnet, OASIS
      declined from 6.6% before to 0% after (p = 0.000) in women given episiotomies
      while it declined from 5.4% to 3% (p = 0.12) in those not given episiotomies.
      After introduction of the EPISCISSORS-60, OASIS was 0% in women with episiotomies
      and 3% in those without episiotomies (p = 0.04). In SVD's at RFL, OASIS was 0% in
      women given episiotomy v 4.7% without episiotomy (p = 0.03). CONCLUSIONS:
      Deliveries with EPISCISSORS-60 episiotomies had lesser OASIS than those without
      episiotomies in both nulliparous OVD's and SVD's. OASIS was lower with
      EPISCISSORS-60 episiotomies than those with eyeballed episiotomies.

PMID- 29571124
TI  - Prevention and management of genital herpes simplex infection during pregnancy
      and delivery: Guidelines from the French College of Gynaecologists and
      Obstetricians (CNGOF).
AB  - OBJECTIVE: Identify measures to diagnose, prevent, and treat genital herpes
      infection during pregnancy and childbirth as well as neonatal herpes infection.
      MATERIALS AND METHODS: Bibliographic search from the Medline and Cochrane Library
      databases and review of international clinical practice guidelines. RESULTS:
      Genital herpes lesions are most often due to HSV-2 (LE2). The risk of HSV
      seroconversion during pregnancy is 1-5% (LE2). Genital herpes lesions during
      pregnancy in a woman with a history of genital herpes is a recurrence. In this
      situation, there is no need for virologic confirmation (Grade B). In pregnant
      women with genital lesions who report they have not previously had genital
      herpes, virological confirmation by PCR and identifying the specific IgG type is
      necessary (professional consensus). A first episode of genital herpes during
      pregnancy should be treated with aciclovir (200 mg 5 times daily) or valaciclovir
      (1000 mg twice daily) for 5-10 days (Grade C), and recurrent herpes during
      pregnancy with aciclovir (200 mg 5 times daily) or valaciclovir (500 mg twice
      daily) (Grade C). The risk of neonatal herpes is estimated at between 25% and 44%
      if a non primary and primary first genital herpes episode is ongoing at delivery
      (LE2) and 1% for a recurrence (LE3). Antiviral prophylaxis should be offered to
      women with either a first or recurrent episode of genital herpes during pregnancy
      from 36 weeks of gestation until delivery (Grade B). Routine prophylaxis is not
      recommended for women with a history of genital herpes but no recurrence during
      pregnancy (professional consensus). A cesarean delivery is recommended if a first
      episode of genital herpes is suspected (or confirmed) at the onset of labor
      (Grade B) or if it occured less than 6 weeks before delivery (professional
      consensus) or in the event of premature rupture of the membranes at term. When a
      recurrence of genital herpes is underway at the onset of labor, cesarean delivery
      is most likely to be considered when the membranes are intact and vaginal
      delivery in cases of prolonged rupture of membranes (professional consensus).
      Neonatal herpes is rare and mainly due to HSV-1 (LE3). In most cases of neonatal
      herpes, mothers have no history of genital herpes (LE3). When neonatal herpes is
      suspected, various samples (blood and cerebrospinal fluid) for HSV PCR must be
      taken to confirm the diagnosis (professional consensus). Any newborn with
      suspected neonatal herpes should be treated with intravenous acyclovir (20 mg/kg
      3 times daily) (grade A) before the PCR results are available (professional
      consensus). The duration of the treatment depends on the clinical form
      (professional consensus) CONCLUSION: There is no formal evidence that it is
      possible to reduce the risk of neonatal herpes in genital herpes during
      pregnancy. However, appropriate care can reduce the symptoms associated with
      herpes and the risk of recurrence at term, as well as cesarean rate because of
      herpes lesions.

PMID- 29571126
TI  - Development of an integrated model for energy systems planning and carbon dioxide
      mitigation under uncertainty - Tradeoffs between two-level decision makers.
AB  - A bi-level fuzzy programming (BFLP) method was developed for energy systems
      planning (ESP) and carbon dioxide (CO2) mitigation under uncertainty. BFLP could
      handle fuzzy information and leader-follower problem in decision-making
      processes. It could also address the tradeoffs among different decision makers in
      two decision-making levels through prioritizing the most important goal. Then, a
      BFLP-ESP model was formulated for planning energy system of Beijing, in which the
      upper-level objective is to minimize CO2 emission and the lower-level objective
      is to minimize the system cost. Results provided a range of decision alternatives
      that corresponded to a tradeoff between system optimality and reliability under
      uncertainty. Compared to the single-level model with a target to minimize system
      cost, the amounts of pollutant/CO2 emissions from BFLP-ESP were reduced since the
      study system would prefer more clean energies (i.e. natural gas, LPG and
      electricity) to replace coal fuel. Decision alternatives from BFLP were more
      beneficial for supporting Beijing to adjust its energy mix and enact its emission
      abatement policy. Results also revealed that the low-carbon policy for power
      plants (e.g., shutting down all coal-fired power plants) could lead to a
      potentially increment of imported energy for Beijing, which would increase the
      risk of energy shortage. The findings could help decision makers analyze the
      interactions between different stakeholders in ESP and provide useful information
      for policy design under uncertainty.

PMID- 29571127
TI  - Increase of lifetime cadmium intake dose-dependently increased all cause of
      mortality in female inhabitants of the cadmium-polluted Jinzu River basin,
      Toyama, Japan.
AB  - BACKGROUND: Exposure to cadmium (Cd) via food is supposed to affect life
      prognosis of inhabitants of Cd-polluted area in Japan. However, there have been
      few reports demonstrating a significant relationship between the amount of Cd
      intake and mortality. We aimed to investigate the relationship between mortality
      and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu
      River basin, Toyama, Japan. METHODS: We conducted a 26-year follow-up survey in
      2407 inhabitants (1208 men and 1199 women) who participated in health
      examinations for screening of renal dysfunction from 1979 to 1984. The
      calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa
      et al., 1989): (mean Cd concentration in rice of the present hamlet * 333.5 g/day
      + 34 MUg/day) * 365 days/year * number of years of residence in the present
      hamlet + 50 MUg/day * 365 days/year * number of years living in Cd non-polluted
      regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in
      this area, 34 ug/day is the Cd intake from foods other than rice in this area,
      and 50 MUg/day is the average intake of Cd in non-polluted areas in Japan.
      Mortality risk ratios of LCd for all and specific causes were estimated after
      adjustments for age at baseline, smoking status, and history of hypertension
      using a Cox hazard model or Fine and Gray competing risks regression model.
      RESULTS: The mortality risk ratios of LCd (+ 1 g) for all causes in women were
      significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd
      for kidney and urinal tract disease, renal diseases, renal failure and toxic
      effects of cadmium were significantly higher in women. CONCLUSIONS: The present
      study documents that individual LCd dose-dependently decreased life prognosis
      over long-term observation in women. LCd was significantly related to the
      increased mortality for renal disease and toxic effect of Cd in women. The result
      provides clear evidence that life prognosis was adversely affected by Cd
      exposure, especially in women.

PMID- 29571128
TI  - Impact of informal electronic waste recycling on metal concentrations in soils
      and dusts.
AB  - Electronic and electrical equipment contains over 1000 different substances,
      including metals. During informal e-waste recycling some of these substances such
      as metals, are released into the environment causing environmental pollution.
      This study assessed the impact of different informal e-waste recycling activities
      (burning, dismantling, and repairing) on metal concentrations in top soils and
      various dust. A comparative cross-sectional study design was adopted to assess
      metal concentrations in top soils and in various dust samples from multiple e
      waste recycling sites. Metal concentrations at e-waste recycling sites were
      compared to the concentrations at control sites in three study locations in
      Nigeria (Lagos, Ibadan, and Aba). In the three study locations, mean metal
      concentrations at the e-waste recycling sites exceeded the concentrations at the
      control sites and the Nigerian standard guideline values by 100 s to 1000 s
      times. Burning sites showed the highest pollution level, followed by dismantling
      sites, then repair sites. Our findings show serious environmental and public
      health concerns. The metal concentrations were also higher than levels reported
      in other studies at the same locations in Nigeria, indicating that the situation
      is worsening. This study provides scientific evidence for an urgent need to
      develop effective strategies to strengthen enforcement of existing e-waste
      regulations in Nigeria.

PMID- 29571125
TI  - NADPH oxidases in traumatic brain injury - Promising therapeutic targets?
AB  - Traumatic brain injury (TBI) is a major cause of death and disability worldwide.
      Despite intense investigation, no neuroprotective agents for TBI have yet
      translated to the clinic. Recent efforts have focused on identifying potential
      therapeutic targets that underlie the secondary TBI pathology that evolves
      minutes to years following the initial injury. Oxidative stress is a key player
      in this complex cascade of secondary injury mechanisms and prominently
      contributes to neurodegeneration and neuroinflammation. NADPH oxidase (NOX) is a
      family of enzymes whose unique function is to produce reactive oxygen species
      (ROS). Human post-mortem and animal studies have identified elevated NOX2 and
      NOX4 levels in the injured brain, suggesting that these two NOXs are involved in
      the pathogenesis of TBI. In support of this, NOX2 and NOX4 deletion studies have
      collectively revealed that targeting NOX enzymes can reduce oxidative stress,
      attenuate neuroinflammation, promote neuronal survival, and improve functional
      outcomes following TBI. In addition, NOX inhibitor studies have confirmed these
      findings and demonstrated an extended critical window of efficacious TBI
      treatment. Finally, the translational potential, caveats, and future directions
      of the field are highlighted and discussed throughout the review.

PMID- 29571129
TI  - Dietary transfer of zinc oxide particles from algae (Scenedesmus obliquus) to
      daphnia (Ceriodaphnia dubia).
AB  - The rapid increase in production and usage of ZnO particles in recent years has
      instigated the concerns regarding their plausible effects on the environment.
      Current study explores the trophic transfer potential of ZnO particles of
      different sizes (50, 100 nm and bulk particles) from algae (Scenedesmus obliquus)
      to daphnia (Ceriodaphnia dubia) and the contribution of ZnO(ions) (effect of
      dissolved Zn ions that remain in test medium after separation NPs) to the overall
      toxicity of ZnO(total) (impact of both particle and dissolved Zn ions). Toxicity
      and uptake of ZnO(total) and ZnO(ions) in algae were found to be dependent on the
      concentration and particle size. Feeding of Zn accumulated algae (517 +/- 28,
      354.7 +/- 61 and 291 +/- 20 ug/g dry wt.) post-exposure to 61 uM of ZnO(total) of
      50, 100 nm and bulk ZnO particles caused a significant decrease in the survival
      (15-20%) of daphnia. A significant amount of Zn accumulation was observed in
      daphnia even after the 48 h depuration period. Biomagnification factor was found
      to be nearly 1 for all the sizes of ZnO particles tested. For 50 nm ZnO, the BMF
      was higher when compared to other two sizes, reaching the mean value of 1.06 +/-
      0.01 at 61 uM. Further analysis revealed that the dietary uptake of different
      sizes of ZnO particles caused ultra-structural damages and degradation of
      internal organs in daphnia.

PMID- 29571130
TI  - Identification of Ligustici Rhizoma et Radix and its adulterants based on their
      chemical constituents by UHPLC-Q/TOF-MS combined with data mining.
AB  - Ligustici Rhizoma et Radix (LR), known as Gaoben (GB) in Chinese, has been used
      in traditional Chinese medicine for more than 2000 years. However, the varieties
      of LR are not well characterized at present, and traditional recognition methods
      have encountered increasing difficulties. This research attempts to distinguish
      different varieties of LR and its adulterants based on their chemical
      composition. A total of 61 representative samples were collected, and their
      varieties were confirmed by combining expert opinion with DNA molecular
      technology. All of the samples were characterized by an UHPLC-Q/TOF-MS method.
      The marker components that may contribute to variety discrimination were
      discerned by a data mining method, and they were then hypothesized, analyzed, and
      identified. A cluster analysis was performed by partial least squares (PLS) based
      on their MS signals. Furthermore, a feature extraction to find out the
      characteristic components, and a correspondence analysis to illustrate the
      corresponding relationship between the varieties and their components, were
      developed. As a result, 71 components were identified, of which 27 components
      were unambiguously identified by comparison with standards. The cluster analysis
      shows that varieties of LR and its adulterant samples exhibited a certain
      classification trend, with butylphthalide, senkyunolide I, senkyunolide A,
      ferulic acid, (Z)-ligustilide, bergapten, levistilide A, vanillic acid,
      isochlorogenic acid C and isochlorogenic acid A as characteristic chemical
      components. The varieties and their components showed a modest correlation. In
      conclusion, our study verified the possibility of discriminating the varieties of
      LR according to their chemical compositions. This research provides a new
      reference for the recognition of LR and its adulterants.

PMID- 29571131
TI  - Nuclear magnetic resonance spectroscopy as a tool for the quantitative analysis
      of water and ions in pharmaceuticals: Example of heparin.
AB  - Heparin is a linear, highly sulfated glycosaminoglycan (GAG), which consists of
      repeating disaccharide units of beta-d-glucuronic acid or alpha-l-iduronic acid
      and alpha-d-glucosamine. While robust analytical approaches exist for the
      characterization of organic composition of heparin preparations, there is a lack
      of methods for the simultaneous quantification of inorganic compounds (water,
      anions, cations) in this matrix. A nuclear magnetic resonance (NMR) spectrometric
      method for heparin characterization described in US Pharmacopeia was extended to
      simultaneous analysis of the inorganic ions (sodium, calcium, and chloride),
      acetate as well as water content. NMR control of these parameters is possible
      with only one sample preparation according to the US Pharmacopeia using just four
      sequential NMR experiments (1H, 2D, 23Na, and 35Cl) with a total measurement time
      less than 20 min. Validation results in terms of precision, reproducibility,
      limit of detection and recovery demonstrated that the developed method is fit-for
      purpose for the authentic heparin samples. The quantitative data for a
      representative set of more than hundred Na- and Ca- heparin and low-molecular
      weight heparin (LMWH) samples were discussed regarding animal origin and the type
      of anticoagulant. NMR spectrometry represents a unique analytical method suitable
      for the simultaneous quantitative control of organic and inorganic composition of
      heparin.

PMID- 29571132
TI  - UGT-mediated metabolism plays a dominant role in the pharmacokinetic behavior and
      the disposition of morusin in vivo and in vitro.
AB  - Morusin is a prenylated flavone isolated from mulberry, the branch and root bark
      of various Morus species, which possesses diverse pharmacological activities.
      However, it lacks extensive studies about its absorption and disposition. This
      study investigated the pharmacokinetic behavior of morusin in rat, and its first
      pass metabolism in situ. The metabolic pathway of morusin was further
      investigated by 12 human recombinant UDP-glucuronosyltransferases (UGTs), 9
      CYP450s, as well as liver and intestinal microsomes. Four mono-glucuronide
      metabolites (M-5-G, M-4'-G, M-2'-G, and MII-2) were identified in rat intestine
      and bile by LC-MS/MS, while three of them were also detected in plasma (M-5-G, M
      4'-G, and MII-2). M-4'-G was the principal conjugate. However, few CYP450
      metabolites were found in rat intestine and bile. Only a small amount of MI-1
      could be detected in rat plasma. UGT1A1, 1A3, 1A7, and 2B7 were the major
      contributors to morusin glucuronidation. Morusin exhibited substrate inhibition
      kinetic characteristics in all UGTs. Clearance rates of M-4'-G in HLM, RLM,
      UGT1A1, UGT1A3, and UGT2B7 were 137.02, 127.55, 32.54, 41.18, and 35.07
      ml/min/mg, respectively. Besides, CYP3A5, 3A4, and 2C19 primarily contributed to
      the oxidative metabolism of morusin. The pharmacokinetic curves of morusin and
      its conjugates presented double peaks, showing that an enterohepatic recycling
      may exist. In conclusion, glucuronidation was confirmed to be the crucial
      metabolic pathway for morusin in vivo, and M-4'-G was the main metabolite.

PMID- 29571133
TI  - LC-MS-based serum fingerprinting reveals significant dysregulation of
      phospholipids in chronic heart failure.
AB  - Cardiac and extracardiac lipid metabolism is known to be significantly altered in
      the course of the heart failure with reduced ejection fraction (HF-REF), however
      the precise mechanisms are not fully elucidated. The aim of the study was to use
      of untargeted metabolomics to identify and validate changes in the blood
      metabolites profile, occurring as a result of HF-REF development. The analyses
      were performed first in the derivation set (36 chronic HF-REF patients and 19
      controls without the disease) and repeated in validation cohort (31 chronic HF
      REF patients and 20 controls). Independent analyses of both sets revealed
      statistically significant decline in intensities of phosphatidylcholine (PC):
      34:4 and 36:5, lysophosphatidylcholine (lyso-PC): 14:0, 15:0, 18:0, 18:2, 20:3,
      lysophosphatidylethanolamine (lyso-PE): 18:1 and 18:2 in chronic HF-REF patients.
      More symptomatic patients and those with ischaemic etiology of HF-REF presented
      greater deficit in phospholipids (PLs) intensities. The decrease of identified
      PLs intensities (as compared to controls) correlated with decreased serum
      cholesterol level, impaired renal function, reduced exercise capacity, enhanced
      ventilatory response and metabolic parameters associated with altered fatty acids
      oxidation. In multiple regression analysis PLs deficit was significantly
      associated with age, carnitines serum intensity, renal function, uric acid,
      cholesterol level. In conclusion, HF-REF is associated with significant
      disturbances in phospholipids metabolism. Greater reduction in serum intensities
      of particular identified PLs is associated with older age, worse clinical
      condition, impaired oxidative muscle metabolism and enhanced catabolic status.

PMID- 29571134
TI  - Determination of oroxylin A and oroxylin A 7-O-d-glucuronide in HepG2 cell lysate
      and subcellular fractions with SPE-UPLC-MS/MS: Cellular pharmacokinetic study to
      indicate anti-cancer mechanisms.
AB  - Targeting therapy of anti-cancer drugs has been gaining increasing attention.
      Cell pharmacokinetics have been used for in vitro disposition evaluation, as well
      as drug-drug interaction for anti-cancer drugs, revealing their fate after
      entering tumor. Flavonoid compound oroxylin A (OA) possesses strong anti-cancer
      effects especially on the liver and breast cancer. However, despite the low
      bioavailability, the disposition of OA and its active metabolite in the target
      cancer cells remained unclear. In current study, a highly sensitive and selective
      solid phase extraction (SPE)-UPLC-MS/MS method was developed and validated to
      simultaneously quantify the concentrations of OA and its major active metabolite
      oroxylin A 7-O-d-glucuronide (OG) in HepG2 cell lysate and multiple subcellular
      organelle fractions. The proposed method appeared to be suitable for the analysis
      with desirable linearity(R2 > 0.99). The relative standard deviations (RSDs) of
      intra- and inter-assay precision and accuracy were less than 9.9% and -7.7%, 8.4%
      and 11% for OA and OG in cell lysate respectively. The intra- precision and
      accuracy was less than 9.5% and -11.3%, 9.4% and 12.3% for OA and OG in
      subcellular organelles respectively. The range of absolute recovery of this
      method in the cell lysate was from 73.1% +/- 1.4% to 87.9% +/- 6.7%. The RSDs of
      matrix effects of the quality control (QC) samples were below 15%. The uptake and
      distribution experiments demonstrated a time-dependent transport characteristic
      in HepG2 cell lines. Furthermore, both OA and OG were mainly distributed into
      nuclei after taken up by the tumor cells. In addition, OG was also distributed
      into mitochondria, which indicates another potential target of OG. The present
      study, for the first time, reports the in vitro cell pharmacokinetics profiles of
      OA and OG in tumor cell lines in vitro.

PMID- 29571135
TI  - Simultaneous monitoring of pazopanib and its metabolites by UPLC-MS/MS.
AB  - Pazopanib is a multi-targeted tyrosine kinase inhibitor (TKI) approved as first
      line treatment for patients with advanced renal cell carcinoma (RCC) and as
      second-line treatment for patients with advanced soft tissue sarcoma (STS)
      previously treated with chemotherapy. The most common adverse events, observed
      during the RCC and STS trials, were gastrointestinal disorders, hypertension,
      fatigue, elevated ALAT and ASAT, but the molecular mechanisms explaining
      pazopanib toxicity remain unclear. Therapeutic activity is considered to be
      mainly dependent on pazopanib exposure as the primary metabolites are inactive or
      display low plasma concentrations, but metabolites may be involved in toxicity as
      relationships between metabolite profiles and toxicity have not been evaluated.
      We report here, for the first time, the validation of a method for the
      simultaneous quantification of pazopanib and semi-quantification of its
      metabolites (relative determination). As there are no standards available,
      pazopanib metabolites were generated with human liver microsomes (HLM) to provide
      controls in the development of an UPLC-MS/MS method for monitoring both pazopanib
      and metabolites. The optimised method was validated for specificity, linearity,
      sensitivity, precision, accuracy, matrix effect and stability. The coefficient of
      variation (CV%) for intra-day and inter-day precision varied from 2.1% to 7.9%
      and 5.6% to 13.1% respectively. The biases varied from -12% to 2.3% (intra-day)
      and 3.8% to 13.1% (inter-day) for accuracy evaluation. Intra-day and inter-day
      precision CV were respectively 20.1% and 19.6% and accuracy biases were between
      20.7% (intra-day) and 3.8% (inter-day) at the limit of quantification. The
      recoveries from matrix samples spiked with pazopanib were respectively 102.6 +/-
      12.9% and 102.5 +/- 1.2% at low and high levels of calibration range. No matrix
      effect was evidenced as demonstrated by the normalised matrix factor values: 1.3
      +/- 0.1 and 1.2 +/- 0.2 respectively measured at low and high part of calibration
      range. A good stability of pazopanib was observed during short term, long term
      and in process storage conditions and after three freeze/thaw cycles. The method
      was applied to clinical samples from three patients treated with pazopanib to
      establish the metabolite profiles (semi-quantitative data) during treatment. The
      assessment of metabolite profiles could be useful to improve our understanding of
      the occurrence of adverse events and to improve pazopanib pharmacokinetic
      pharmacodynamic relationships.

PMID- 29571136
TI  - In line monitoring of the powder flow behavior and drug content in a Fette 3090
      feed frame at different operating conditions using Near Infrared spectroscopy.
AB  - Near infrared (NIR) spectroscopy was used to determine the drug concentration in
      3% (w/w) acetaminophen blends within the complex flow regime of the tablet press
      feed frame just before tablet compaction. NIR spectra also provided valuable
      information on the powder flow behavior within the feed frame and were used to
      track when a process enters or leaves the steady state. A partial least squares
      regression calibration model was developed with powder mixtures that varied from
      1.5 to 4.5% (w/w) by obtaining 135 spectra after steady state for each
      concentration while the feed frame and die disc operated at 30.5 revolutions per
      minute (rpm). The calibration model determined drug concentration in validation
      blends with a root mean square error of prediction and bias below 0.1% (w/w). The
      robustness of the NIR calibration model was evaluated by determining the effect
      of variation on the operating conditions (paddle wheel speed and die disc speed)
      on NIR predictions. This work found that the paddle wheel speed can be increased
      up to 30% and the die disc speed decrease 10% without affecting NIR predictions.
      The results demonstrated that paddle wheel speed has a significant effect on the
      wave powder behavior (frequency and amplitude) but does not have significant
      effect on the mass hold-up within feed frame. The die disc speed does not affect
      wave powder behavior but affects significantly the mass hold-up inside the feed
      frame. This information can be used to reduce the tablet weight variability and
      ensure that this critical attribute is met.

PMID- 29571137
TI  - Efficient nano titanium electrode via a two-step electrochemical anodization with
      reconstructed nanotubes: Electrochemical activity and stability.
AB  - A two-step anodization method was used to prepare an efficient nano Ti electrode
      (ENTE), based on the nano Ti electrode (NTE) that was synthesized by the
      traditional anodization method. The result of FESEM showed there were many
      nanopores and nanoparticles on the surface of the ENTE. Compared with Ti
      electrode, the ENTE exhibited an increased electrochemical activity of nitrate
      reduction, attributing to its ~1.09-fold higher reduction peak current density.
      Values of average current efficiency towards nitrate reduction indicated that the
      electrochemical properties of different electrodes were raised in the order of
      ENTE (0.36) > NTE (0.25) > Ti electrode (0.15). The ENTE exhibited a ~3.33-fold
      higher electroactive surface area than that of Ti electrode. The higher current
      density throughout the 1000 s and the ~1.27-fold higher final current density at
      1000 s suggested that the ENTE had a higher stability for nitrate
      electroreduction. The nitrate reduction efficiency increased with the increasing
      of initial nitrate-nitrogen concentration and temperature. Similar effect was
      obtained from current density below 50 mA cm-2. And under the neutral condition,
      a higher nitrate reduction efficiency was achieved. The curved surface and higher
      surface area due to the nanopores of the ENTE increased the nitrate concentration
      in the EDL and enhanced the potential of individual nitrate ions in the diffuse
      layer exponentially. This research provided a new route to assess a nano
      electrode with high stability and a clear reaction mechanism in EDL.

PMID- 29571138
TI  - Mitigation of harmful indoor organic vapors using plug-flow unit coated with 2D g
      C3N4 and metallic Cu dual-incorporated 1D titania heterostructure.
AB  - Herein, a plug-flow reactor coated with one-dimensional (1D) TiO2 nanotube (TNT)
      heterostructures incorporated with g-C3N4 (CN) and metallic Cu (CN/Cu/TNT)
      nanocomposite and irradiated by a daylight lamp was newly applied for the
      mitigation of harmful indoor organic vapors. The CN/Cu/TNT catalyst showed high
      mitigation efficiency for all target pollutants, followed by Cu-incorporated TNT
      (Cu/TNT), CN-incorporated TNT (CN/TNT), TNT, and TiO2, in that order. The order
      of their photocatalytic activities agrees with that of the electron-hole
      separation rates determined from their photoluminescence emission spectra. The
      mitigation efficiency of the CN/Cu/TNT catalyst increased as the CN-to-Cu/TNT
      percentage was increased from 1% to 10%, but subsequently decreased as the CN-to
      Cu/TNT percentage increased to 20%. The mitigation efficiencies of the CN/Cu/TNT
      catalyst decreased with increasing relative humidity, feed pollutant
      concentrations, and airstream flow rates. However, in most cases, the reaction
      rates of the target compounds increased when the feed concentration was increased
      from 1 to 5 ppm. The mineralization rates of all target pollutants were lower
      than the corresponding photocatalytic mitigation rates, which could be ascribed
      to the production of CO and organic intermediates observed during the
      photocatalysis of the target pollutants. Nevertheless, the intermediates formed
      during the photocatalytic mitigation process would not cause significant adverse
      health effects to building occupants, because their concentrations were far below
      their exposure or threshold limit values. A probable mechanism for the
      photocatalytic mitigation of the organic vapors by the CN/Cu/TNT catalyst under
      daylight illumination was also proposed.

PMID- 29571139
TI  - Effect of the structure of stacked electro-Fenton reactor on treating
      nanofiltration concentrate of landfill leachate.
AB  - The membrane concentrate from landfill leachate has great potential risks of the
      environmental pollution. The aim of this study was to investigate the structure
      effect of stacked electro-Fenton (EF) reactor on the nanofiltration (NF)
      concentrate treatment from landfill leachate. The stacked EF reactor was
      constructed with a carbon-PTFE gas diffusion cathode and an IrO2-Ta2O5 anode with
      different electrode spacings (i.e., 2, 5, 10, and 40 mm) and electrode pairs
      (i.e., 1, 3, 6, and 9). Results showed that smaller electrode spacing and more
      electrode pairs in the stacked EF reactor improved the COD removal in the NF
      concentrate treatment. The specific energy consumption decreased with smaller
      electrode spacing but increased with more electrode pairs. Under the current
      density of 15 mA cm-2, Fe2+ dosage of 560 mg L-1, the stacked EF reactor with 9
      electrode pairs and the electrode spacing of 2 mm removed 71 +/- 6% of the total
      COD in the NF concentrate within 6 h and the specific energy consumption was 207
      +/- 20 kWh?kg COD-1. The COD removal was kept stable in the stacked EF reactor
      within 3 cycles of operation. Three-dimensional fluorescence spectroscopic and
      gas chromatographic mass spectrometric analysis showed that humic acids and
      aromatic proteins were efficiently degraded in the EF process and large amount of
      aromatic hydrocarbons was detected in the treated NF concentrate. Our stacked EF
      reactor could be used to treat leachate concentrates with effectively degradation
      of the refractory organic pollutants.

PMID- 29571140
TI  - Immobilization of peroxidase on polypyrrole-cellulose-graphene oxide
      nanocomposite via non-covalent interactions for the degradation of Reactive Blue
      4 dye.
AB  - In the present study novel polypyrrole-cellulose-graphene oxide nanocomposite
      (PCeGONC) was employed for the immobilization of ginger peroxidase (GP) via
      simple adsorption mechanism. Immobilization of enzyme on the obtained support
      resulted in enhancement of the enzyme activity. The recovery of activity was 128%
      of the initial activity. Consequently, in 3 h stirred batch treatment, PCeGONC
      bound GP exhibited higher decolorization efficiency (99%) for Reactive Blue 4 (RB
      4) dye as compared to free GP (88%). The immobilized GP exhibited higher
      operational stability and retained approximately 72% of its initial activity even
      after ten sequential cycles of dye decolorization in batch process. The kinetic
      characterization of PCeGONC bound GP revealed slightly lower Km and 3.3 times
      higher Vmax compared to free GP. Degraded products were identified on the basis
      of GC-MS analysis and degradation pathway was proposed accordingly which confirms
      enzymatic breakdown of RB 4 into low molecular weight compounds. Genotoxic
      assessment of GP treated RB 4 revealed significant reduction of its genotoxic
      potential. In-silico analysis identified that binding site of PCeGONC on enzyme
      is distinct and lies far away from the active site of the enzyme. Furthermore, it
      also revealed higher affinity of 1-hydroxybenzotriazole (a redox mediator) and RB
      4 for PCeGONC bound enzyme as compared to the free enzyme. This is in consensus
      with the observed decrease in Km of the immobilized GP.

PMID- 29571141
TI  - Use of aged sludge bioaugmentation in two-stage activated sludge system to
      enhance the biodegradation of toxic organic compounds in high strength
      wastewater.
AB  - This research investigates the toxic organic compounds biodegradation efficiency
      of two-stage activated sludge systems with (bioaugmented) and without aged sludge
      bioaugmentation (non-bioaugmented). The influent was a mixture of leachate and
      agriculture wastewater (1:1, v/v), used as the representative high strength
      wastewater. The bioaugmented and non-bioaugmented systems were operated in
      parallel, with three levels (low, moderate, and high) of concentrations of
      organics, nitrogen, and toxic organic compounds in the influent (conditions 1, 2,
      and 3). The results showed that both systems could efficiently degrade the
      organic compounds. Nevertheless, the toxic organic compounds biodegradation
      efficiency of the bioaugmented system was higher than that of the non
      bioaugmented one. The bioaugmentation enhanced the overall removal efficiency
      under conditions 1 and 2. However, the bioaugmented system became less effective
      under condition 3. Further analysis indicated that the bacterial groups essential
      to the toxic organic compounds biodegradation were abundant in the aged sludge,
      including heterotrophic bacteria, heterotrophic nitrifying bacteria, and
      nitrifying bacteria. The abundance of the effective bacteria improved the
      biodegradation and wastewater treatment performance of the bioaugmented system.
      In essence, the aged sludge bioaugmentation is a viable and eco-friendly solution
      to improving the treatment efficiency of the biological activated sludge system,
      despite limited biodegradation efficiency in an elevated compounds-concentration
      environment.

PMID- 29571142
TI  - Formation of PFAAs in fish through biotransformation: A PBPK approach.
AB  - A physiologically-based pharmacokinetic (PBPK) model for perfluorinated alkyl
      acids (PFAAs) in rainbow trout has been updated to include formation of
      perfluorooctanoic acid (PFOA) from the biotransformation of 8:2 fluorotelomer
      carboxylic acid (8:2 FTCA). The updated model is dynamic and simulates both
      uptake and depuration phases. Two empirical studies are used to parameterize and
      test the model. In the first case, parameters related to fecal elimination and
      protein binding were optimized. In the second case, parameters were sourced
      either from literature or from optimized values based on the first study to test
      model performance. Optimization of parameters resulted in a decrease in the
      difference between experimental data and simulation results by 57 and 23 percent
      for the first and the second case, respectively, compared to the original case.
      Sensitivity analysis was performed to identify important parameters, and
      uncertainty in model prediction propagated by these parameters was assessed using
      Monte Carlo analysis. For each case, 80 and 89 percent, respectively, of median
      predicted values were within the limits of experimental error when comparing
      simulated and experimental data. This is the first toxicokinetic model that
      incorporates biotransformation of PFAA precursors and simultaneously predicts the
      distribution of the precursor and metabolite in different tissues. The model is
      mechanistic, and could be applied to simulate a variety of scenarios by using the
      organism-specific physiological properties compiled here with other chemical
      specific parameters (e.g. protein interactions).

PMID- 29571143
TI  - Use of ozone-biofiltration for bulk organic removal and disinfection byproduct
      mitigation in potable reuse applications.
AB  - The purpose of this research was to investigate the impacts of ozone dose and
      empty bed contact time (EBCT) in ozone-biofiltration systems on disinfection
      byproduct (DBP) formation potential. The data were used to evaluate the
      possibility of using DBP formation potential as an alternative guideline for
      total organic carbon (TOC) removal in potable reuse applications. A pilot-scale
      ozone-biofiltration system was operated with O3/TOC ratios ranging from 0.1 to
      2.25 and EBCTs ranging from 2 to 20 min. The biofiltration columns contained
      anthracite or biological activated carbon (BAC). Bench-scale chlorination was
      performed using the uniform formation conditions (UFC) approach, and quenched
      samples were analyzed for total trihalomethanes (TTHMs) and regulated haloacetic
      acids (HAA5s). The data demonstrated that ozone-biofiltration achieved TOC
      removals ranging from ~10 to 30%, depending on operational conditions, but
      biofiltration without ozone generally achieved <10% TOC removal. UFC testing
      demonstrated that ozone alone was efficient in transforming bulk organic matter
      and reducing DBP formation potential by 10-30%. The synergistic combination of
      ozone and biofiltration achieved average overall reductions in TTHM and HAA5
      formation potential of 26% and 51%, respectively. Finally, a maximum TOC
      concentration of 2.0 mg/L was identified as a recommended treatment target for
      reliable compliance with TTHM and HAA5 regulations for potable reuse systems in
      the United States.

PMID- 29571144
TI  - Sequential application of Fenton and ozone-based oxidation process for the
      abatement of Ni-EDTA containing nickel plating effluents.
AB  - Treatment of Ni-EDTA in industrial nickel plating effluents was investigated by
      integrated application of Fenton and ozone-based oxidation processes.
      Determination of integrated sequence found that Fenton oxidation presented higher
      apparent kinetic rate constant of Ni-EDTA oxidation and capacity for
      contamination load than ozone-based oxidation process, the latter, however, was
      favorable to guarantee the further mineralization of organic substances,
      especially at a low concentration. Serial-connection mode of two oxidation
      processes was appraised, Fenton effluent after treated by hydroxide precipitation
      and filtration negatively affected the overall performance of the sequential
      system, as evidenced by the removal efficiencies of Ni2+ and TOC dropping from
      99.8% to 98.7%, and from 74.8% to 66.6%, respectively. As a comparison, O3/Fe2+
      oxidation process was proved to be more effective than other processes (e.g. O3
      Fe2+, O3/H2O2/Fe2+, O3/H2O2-Fe2+), and the final effluent Ni2+ concentration
      could satisfied the discharge standard (<0.1 mg L-1, China) under the optimal
      conditions (H2O2 dosage of 1.0 mL L-1, Fe2+: H2O2 mole ratio of 1.46, and
      reaction time of 10 min for Fenton reaction, initial influent pH of 3.0, O3
      dosage of 252 mg L-1, Fe2+ of 150 mg L-1, and reaction time of 30 min for O3/Fe2+
      oxidation). Furthermore, pilot-scale test was carried out to study the practical
      treatability towards the real nickel plating effluent, revealing the effective
      removal of some other co-existence contaminations. And Fenton reaction has
      contributed most, with the percentage ranging from 72.41% to 93.76%. The economic
      cost advantage made it a promising alternative to the continuous Fenton
      oxidation.

PMID- 29571145
TI  - Atmospheric concentrations and gas-particle partitioning of PCDD/Fs and dioxin
      like PCBs around Hochiminh city.
AB  - Atmospheric PCDD/Fs and dl-PCBs samples were collected in Hochiminh city, Vietnam
      to address the effect of meteorological parameters, especially rainfall, on the
      occurrence and gas/particle partitioning of these persistent organic pollutants.
      The results indicate that PCDD/Fs and dl-PCBs concentrations in industrial site
      are higher than those measured in commercial and rural sites during both rainy
      and dry seasons. In terms of mass concentration, ambient PCDD/F levels measured
      in dry season are significantly higher than those measured in rainy season while
      dl-PCB levels do not vary significantly between rainy and dry seasons. The
      difference could be attributed to different gas/particle partitioning
      characteristics between PCDD/Fs and dl-PCBs. PCDD/Fs are found to be mainly
      distributed in particle phase while dl- PCBs are predominantly distributed in gas
      phase in both rainy and dry seasons. Additionally, Junge-Pankow and Harner
      Bidleman models are applied to better understand the gas/particle partitioning of
      these pollutants in atmosphere. As a results, both PCDD/Fs and dl-PCBs are under
      non-equilibrium gas/particle partitioning condition, and PCDD/Fs tend to reach
      equilibrium easier in rainy season while there are no clear trend for dl-PCBs.
      Harner-Bidleman model performs better in evaluating the gas/particle partitioning
      of PCDD/Fs while Junge-Pankow model results in better prediction for dl-PCBs.

PMID- 29571146
TI  - Occurrence and partitioning behavior of organophosphate esters in surface water
      and sediment of a shallow Chinese freshwater lake (Taihu Lake): Implication for
      eco-toxicity risk.
AB  - Organophosphate esters (OPEs) are ubiquitous in the aquatic environment, which
      have been considered or suspected as carcinogens and neurotoxicants. In this
      study, the occurrence, spatial distribution, potential sources, partitioning
      character and potential risks of OPEs in the surface water and sediment collected
      from Taihu Lake were investigated. The concentrations of ?12 OPEs varied from 1.0
      * 102 to 1.7 * 103 ng/L for the surface water and from 8.1 to 4.2 * 102 ng/g dw
      for the sediment. Trimethyl phosphate (TEP) was the predominant congener in the
      surface water, while Tris(2-ethylhexyl) phosphate (TEHP) in the sediment.
      Positive correlations between OPEs indicated that they may have the same sources
      and/or similar environmental behavior. The pseudo-partitioning values of OPEs
      ranged from 0.59 to 6.5 * 104 L/kg. TEHP has the highest pseudo-partitioning
      coefficient, which indicated that TEHP inclined to be enriched in the sediment in
      Taihu Lake. Risk assessment (RQ) showed that individual OPEs in the surface water
      and sediment posed no/low risk to aquatic organisms, except 2-Ethylhexyl diphenyl
      phosphate (EHDPP) (moderate risk) in water.

PMID- 29571147
TI  - Counteranion-dependent sorption of imidazolium- and benzimidazolium-based ionic
      liquids by soot.
AB  - Sorption of ionic liquids (ILs) to soil and porous materials as affected by
      anions was observed, but scarce effort has been focused on addressing the role of
      counteranions in sorption and the associated underlying mechanisms. In this work,
      two series of 1-butyl-3-methylimidazolium- (Bmim-) and N-butyl, methyl
      benzimidazolium-based (Bmbim-based) ILs coupled with different counteranions were
      prepared to investigate the effect of anions on IL sorption by soot. The octanol
      water partition coefficient (Kow) and the ion-pair formation constant at infinite
      dilution in water (KIP degrees ) of ILs were independently measured to explore
      the contribution of counteranion-dependent hydrophobicity and ion-pair. A wide
      range of sorption coefficients (Kd) of ILs were achieved with values varying from
      59.8 to 344.3 L.kg-1 for Bmbim-based ILs and from 253.4 to 489.7 L kg-1 for Bmbim
      based ILs. Compared with other anions, bis(trifluoromethanesulphonyl)imide
      ([Tf2N]-) and hexafluorophosphate ([PF6]-) exhibit tighter association with IL
      cations in aqueous solution due to their larger Kow and higher KIP degrees .
      Positive linear relationships between log KIP degrees  and Kd and between log Kow
      and Kd evidenced that the counteranion-dependent sorption of ILs relies on the
      association strengths of IL cations and counteranions, which further influence
      the hydrophobicity/hydrophilicity of ion pairs. Compared with that of strongly
      coordinating anions (such as [CH3SO3]-, [CF3COO]-, [BF4]-, [CF3SO3]-, and [Cl]-),
      the addition of weakly coordinating anions (such as [Tf2N]- and [PF6]-) in
      solution contributes to markedly large sorption enhancement of ILs. Consequently,
      the contribution of different counteranions on IL sorption is essentially based
      on the formation of ion pair with different KIP degrees  and Kow in aqueous
      solution.

PMID- 29571148
TI  - Microbial vanadium (V) reduction in groundwater with different soils from
      vanadium ore mining areas.
AB  - This work investigated the potential of vanadium (V) (V(V)) bioreduction by using
      soils sampled from four main kinds of vanadium ore mining areas, i.e. vanadium
      titanomagnetite, stone coal, petroleum associated minerals and uvanite as
      inocula. During a typical operation cycle of 60 h, the soils from vanadium
      titanomagnetite area and petroleum associated minerals area exhibited higher V(V)
      removal efficiencies, about 92.0 +/- 2.0% and 91.0 +/- 1.9% in comparison to 87.1
      +/- 1.9% and 69.0 +/- 1.1% for the soils from uvanite and stone coal areas,
      respectively. Results from high-throughput 16 S rRNA gene pyrosequencing analysis
      reflect the accumulation of Bryobacter and Acidobacteriaceae with capabilities of
      V(V) reduction, accompanied with other functional species. This study is helpful
      to search new functional species for V(V) reduction and to develop in situ
      bioremediations of V(V) polluted groundwater.

PMID- 29571149
TI  - Alkaloids from Corydalis decumbens suppress neuronal excitability in primary
      cultures of mouse neocortical neurons.
AB  - Eight previously undescribed alkaloids, named corydemine, dihydrocorydemine,
      corydedine, 8,13-dioxo-14-hydroxytetrahydropalmatine, egenine-alpha-N-oxide,
      egenine-beta-N-oxide, 7'-O-ethylegenine-alpha-N-oxide, and 7'-O-ethylegenine-beta
      N-oxide, together with three known ones, muramine, l-tetrahydropalmatine, and (+)
      egenine, were isolated from the bulbs of Corydalis decumbens. Their structures
      were elucidated by comprehensive spectroscopic analysis and chemical correlation.
      The isolated compounds were tested for their ability to modulate neuronal
      excitability in primary cultured neocortical neurons. Four of the compounds,
      corydemine, dihydrocorydemine, muramine, and l-tetrahydropalmatine, inhibited
      neuronal excitability with IC50 values of 3.6, 16.7, 13.5 and 14.0 MUM,
      respectively.

PMID- 29571150
TI  - Metabolomic analysis applied to chemosystematics and evolution of megadiverse
      Brazilian Vernonieae (Asteraceae).
AB  - Vernonia sensu lato is the largest and most complex genus of the tribe Vernonieae
      (Asteraceae). The tribe is chemically characterized by the presence of
      sesquiterpene lactones and flavonoids. Over the years, several taxonomic
      classifications have been proposed for Vernonia s.l. and for the tribe; however,
      there has been no consensus among the researches. According to traditional
      classification, Vernonia s.l. comprises more than 1000 species divided into
      sections, subsections and series (sensu Bentham). In a more recent
      classification, these species have been segregated into other genera and some
      subtribes were proposed, while the genus Vernonia sensu stricto was restricted to
      22 species distributed mainly in North America (sensu Robinson). In this study,
      species from the subtribes Vernoniinae, Lepidaploinae and Rolandrinae were
      analyzed by UHPLC-UV-HRMS followed by multivariate statistical analysis. Data
      mining was performed using unsupervised (HCA and PCA) and supervised methods
      (OPLS-DA). The HCA showed the segregation of the species into four main groups.
      Comparing the HCA with taxonomical classifications of Vernonieae, we observed
      that the groups of the dendogram, based on metabolic profiling, were in
      accordance with the generic classification proposed by Robinson and with previous
      phylogenetic studies. The species of the genera Stenocephalum, Stilpnopappus,
      Strophopappus and Rolandra (Group 1) were revealed to be more related to the
      species of the genus Vernonanthura (Group 2), while the genera Cyrtocymura,
      Chrysolaena and Echinocoryne (Group 3) were chemically more similar to the genera
      Lessingianthus and Lepidaploa (Group 4). These findings indicated that the
      subtribes Vernoniinae and Lepidaploinae are non-chemically homogeneous groups and
      highlighted the application of untargeted metabolomic tools for taxonomy and as
      indicators of species evolution. Discriminant compounds for the groups obtained
      by OPLS-DA were determined. Groups 1 and 2 were characterized by the presence of
      3',4'-dimethoxyluteolin, glaucolide A and 8-tigloyloxyglaucolide A. The species
      of Groups 3 and 4 were characterized by the presence of putative acacetin 7-O
      rutinoside and glaucolide B. Therefore, untargeted metabolomic approach combined
      with multivariate statistical analysis, as proposed herein, allowed the
      identification of potential chemotaxonomic markers, helping in the taxonomic
      classifications.

PMID- 29571151
TI  - Folate homeostasis in epileptic rats.
AB  - Folate is involved in metabolic processes and it has been implicated in both
      aggravation and amelioration of seizures. The aim of the current work was to
      study the effect of chronic temporal lobe epilepsy (TLE) on the plasma and brain
      concentrations of folate and on its uptake carriers in the brain - the reduced
      folate carrier (RFC), folate receptor alpha (FRalpha) and proton coupled folate
      transporter (PCFT). We utilized the rat lithium pilocarpine model for TLE.
      Approximately two months following status epilepticus, rats with spontaneous
      recurrent seizures (SRS) were sacrificed for brain and plasma folate
      concentration analyses and folate uptake carrier expression studies. RT-PCR and
      western blot analyses were utilized for quantification of folate carriers' mRNAs
      and proteins, respectively. The distribution of folate carriers in the brain was
      studied using immunohistochemistry. In the SRS rats we found lower plasma
      concentrations (10 +/- 0.9 in control vs. 6.6 +/- 1.6 ng/ml in SRS, P < 0.05),
      but preserved cortical and increased hippocampal levels of folate (0.5 +/- 0.1 in
      control vs. 0.9 +/- 0.2 ng/mg in SRS, P = 0.055). Hippocampus - to - plasma ratio
      of folate concentration was 3-fold higher in the SRS group, compared with the
      controls (0.13 +/- 0.03 vs. 0.04 +/- 0.02, respectively; P < 0.01). mRNA and
      protein levels of the folate uptake carriers did not differ between SRS rats and
      controls. However, immunofluorescent staining quantification revealed that the
      emission intensity of both RFC and FRalpha was elevated 8-fold and 4-fold,
      respectively, in hippocampal CA1 neurons of SRS rats, compared to controls (P <
      0.01). PCFT was unquantifiable. If corroborated by complementary research in
      humans, the findings of this study may be utilized clinically for supplemental
      therapy planning, in imaging the epileptic focus, and for drug delivery into the
      epileptic brain. Further studies are required for better elucidating the clinical
      and mechanistic significance of altered folate balances in the epileptic brain.

PMID- 29571152
TI  - Comparative efficacy of unique antiepileptic drug regimens in focal epilepsy: An
      exploratory study.
AB  - OBJECTIVE: To compare efficacy of unique antiepileptic drug (AED) polytherapy
      regimens among patients with focal epilepsy. METHODS: From a longitudinal study
      of AED treatment, we identified patients with active focal epilepsy who had
      attempted at least two unique AED regimens (mono-, duo-, or tri-therapy).
      Efficacy was defined as the presence of at least one six-month period of
      continuous seizure freedom during exposure to a regimen. To control for
      individual variations in response and epilepsy severity, we used within-patient
      comparison approaches, in which we: 1) compared head-to-head unique regimens
      tried within the same patients; 2) compared one regimen versus aggregate of other
      regimens attempted in that patient; and 3) compared aggregated monotherapy versus
      polytherapy regimens. RESULTS: 757 patients met our criteria and had collectively
      attempted 170 unique regimens. In the head-to-head analysis, lamotrigine
      monotherapy was more effective than phenytoin monotherapy. Two regimens were more
      effective than the aggregate of other regimens attempted:
      levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other
      regimens exhibited slightly better efficacy but did not reach statistical
      significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine.
      Patients who previously attempted at least four regimens had slightly better
      outcomes on polytherapy than monotherapy, though this was not significant.
      SIGNIFICANCE: We identified two unique regimens more likely to be associated with
      >=6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and
      lamotrigine monotherapy. Polytherapy may be an effective alternative to
      monotherapy for patients with focal epilepsy and persistent seizures.

PMID- 29571153
TI  - Tangential cranial ballistic impact: An illustration of the limitations of post
      mortem CT scan?
AB  - Post-mortem imaging has become more frequently used in forensic procedures,
      notably in a ballistic context. Despite many advances in this field, the
      interpretation of computed tomography (CT) can be a very complex matter. Our case
      illustrates the difficulties of interpretation after quasi-tangential cranial
      ballistic impact and keyhole wounds. These wounds are difficult to visualize on
      CT and are among the factors complicating the precise determination of
      ballistics. These sources of error remind us that CT findings must be interpreted
      in close comparison with autopsy findings.

PMID- 29571154
TI  - Postmortem interval estimation using the animal model of postmortem gas volume
      changes.
AB  - It is important to estimate the postmortem interval in forensic autopsy. Many
      methods to estimate the postmortem interval have been reported, and are typically
      associated with internal examination. However, there are issues such as rejection
      of autopsy by the family and a lack of forensic doctor in internal examination.
      Therefore, it is necessary to develop new methods, such as autopsy imaging, that
      can substitute for internal examination. Here, we first evaluated whether gas
      volume in the body increased with postmortem interval. Time-dependent X-ray CT
      imaging of euthanized Crl:CD (SD) rats (n = 3) was performed immediately after
      euthanasia and at seven subsequent time points up to 168 h (7 days) at 24-hour
      intervals. The data revealed that gas volume in the body increased in a time
      dependent manner. Next, we reconstructed 3D images of isolated gas and calculated
      the gas volume using Amira software. In all cases, the volume of both portal
      venous gas and intestinal gas increased in a time-dependent manner. The volume of
      portal venous gas increased exponentially, while the volume of intestinal gas
      increased in a linearly with time. These data might be suggested that the
      postmortem gas volume change is one of indicators for estimating the postmortem
      interval. In addition, it would be possible to estimate more accurate postmortem
      interval by combining not only gas volume changes at the above two sites but also
      gas volume changes of the other sites such as heart cavities, kidney parenchyma,
      or abdominal aorta.

PMID- 29571155
TI  - Synthesis of novel 4-functionalized 1,5-diaryl-1,2,3-triazoles containing
      benzenesulfonamide moiety as carbonic anhydrase I, II, IV and IX inhibitors.
AB  - The design, synthesis and biological evaluation of a library of 1,2,3-triazole
      carboxylates incorporating carboxylic acid, hydroxymethyl, carboxylic acid
      hydrazide, carboxamide and benzenesulfonamide moieties is disclosed. All the
      novel compounds were investigated for their inhibition potential against carbonic
      anhydrase (CA, EC 4.2.1.1) human (h) isoforms hCA I, II, IV and IX, well
      established drug targets. The cytosolic isoform hCA I was inhibited with Ki's
      ranging between 53.2 nM and 7.616 MUM whereas the glaucoma associated cytosolic
      isoform hCA II was inhibited with Ki's in the range 21.8 nM-0.807 MUM. The
      membrane bound isoform hCA IV, involved in glaucoma and retinitis pigmentosa
      among others, was effectively inhibited by some of these compounds with Ki < 60
      nM, better than the reference drug acetazolamide (AAZ). The tumor associated
      isoform hCA IX, a recently validated antitumor/antimetastatic drug target, was
      also effectively inhibited by some of the new sulfonamides, which possess thus
      the potential to be used as tools for exploring in more details the selective
      inhibition of hCAs involved in various pathologies.

PMID- 29571156
TI  - Simple 2(5H)-furanone derivatives with selective cytotoxicity towards non-small
      cell lung cancer cell line A549 - Synthesis, structure-activity relationship and
      biological evaluation.
AB  - A series of 5-alkoxy derivatives of 3,4-dichloro-5-hydroxyfuran-2-(5H)-one
      (mucochloric acid, MCA) were obtained and subsequently subjected to modification
      in the C-4 position of 2(5H)-furanone ring. The cytotoxicity of newly synthesized
      compounds was evaluated in MTT assay against non-small cell lung cancer (A549)
      and healthy lung epithelial cell line (BEAS-2B). The derivatives containing a
      branched alkoxy substituent in the C-5 position demonstrated the highest
      anticancer properties, whereas modification of compounds in the C-4 position of
      2(5H)-furanone ring only slightly improve their antiproliferative properties.
      Compounds 12 and 15 exhibited the best selectivity towards A549 cells and were
      also evaluated in a panel of cancer cell lines of different origin. Further
      investigation revealed that treatment of A549 cell line with compounds 12 and 15
      led to G2 phase cell cycle arrest and induction of caspase-independent cell
      death. Moreover, compound 12 was found to act synergistically with erlotinib.

PMID- 29571158
TI  - Molecular features of nonionic detergents involved in the binding kinetics and
      solubilization efficiency, as studied in model (Langmuir films) and biological
      (Erythrocytes) membranes.
AB  - The effect of the nonionic detergents Brij-98 and Brij-58 over human erythrocytes
      was studied through quantitative hemolysis and in Langmuir films. Hemolytic tests
      revealed that Brijs are stronger membrane solubilizers than Triton X-100 (TX
      100), with effective detergent/lipid ratios of 0.18 and 0.37 for Brij-98 and Brij
      58, respectively. Experiments with Langmuir films provided significant
      information on the kinetics and thermodynamics of detergent-membrane interaction.
      The adsorption (ka) and desorption (kd) rate constants of Brijs were lower than
      those of TX-100. In the case of ka, that is probably due to their larger
      hydrophilic head (with twice (20) the oxyethylene units of TX-100). As for the
      thermodynamic binding constant, the linear and longer hydrophobic acyl chains of
      Brijs favor their stabilization in-between the lipids, through London van der
      Waals forces. Consequently, Kb,m values of Brij-98 (12,500 M-1) and Brij-58
      (19,300 M-1) resulted higher than TX-100 (7500 M-1), in agreement with results
      from the hemolytic tests. Furthermore, Brij-58 binds with higher affinity than
      Brij-98 to bilayers and monolayers, despite its shorter (palmitic) hydrocarbon
      chain, showing that unsaturation restrains the detergent insertion into these
      environments. Our results provide significant information about the mechanism of
      interaction between Brijs and membranes, supporting their distinct solubilization
      effect.

PMID- 29571159
TI  - Selenium nanocomposites as multifunctional nanoplatform for imaging guiding
      synergistic chemo-photothermal therapy.
AB  - A multifunctional selenium nanocomposite (selenium@silica core-shell nanoshperes
      for loading indocyanine green(ICG)/Doxorubicin(DOX)) was fabricated to reach
      visible and efficient cancer treatment. The Se@SiO2-ICG nanocomposites could be
      used not only as excellent photothermal agents but also as carriers for DOX
      delivery. In addition, the Se@SiO2-ICG/DOX nanocomposites exhibited excellent
      fluorescence imaging and infrared imaging performance. Tumor could be effectively
      inhibited by Se@SiO2-ICG/DOX due to the triple treatment of photothermal effect
      and chemotherapy of selenium and DOX. Thus, the Se@SiO2-ICG/DOX nanocomposites
      have a great potential in imaging guiding synergistic treatment of cancer.

PMID- 29571157
TI  - Antimalarial agents against both sexual and asexual parasites stages: structure
      activity relationships and biological studies of the Malaria Box compound 1-[5-(4
      bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine
      (MMV019918) and analogues.
AB  - Therapies addressing multiple stages of Plasmodium falciparum life cycle are
      highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1
      [5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was
      selected from the MMV Malaria Box for its dual activity against both asexual
      stages and gametocytes. In-depth structure-activity relationship studies and
      cytotoxicity evaluation led to the selection of 25 for further biological
      investigation. The potential transmission blocking activity of 25 versus P.
      falciparum was confirmed through the standard membrane-feeding assay. Both 1 and
      25 significantly prolonged atrioventricular conduction time in Langendorff
      isolated rat hearts, and showed inhibitory activity of Ba2+ current through
      Cav1.2 channels. An in silico target-fishing study suggested the enzyme
      phosphoethanolamine methyltransferase (PfPMT) as a potential target. However,
      compound activity against PfPMT did not track with the antiplasmodial activity,
      suggesting the latter activity relies on a different molecular target.
      Nevertheless, 25 showed interesting activity against PfPMT, which could be an
      important starting point for the identification of more potent inhibitors active
      against both sexual and asexual stages of the parasite.

PMID- 29571160
TI  - One-step selective screening of bioactive molecules in living cells using sulfur
      doped microporous carbon.
AB  - A metal-free electrode using heteroatom-doped microporous carbon was fabricated
      for the ultrasensitive monitoring of mono-bioactive molecules and the selective
      signaling of dopamine (DA) secreted by living cells. The constructed electrode
      based on sulfur-doped microporous carbon (S-MC) shows a high surface area, a
      spherical construction, numerous carbon chain defects, and microporous
      structures, which are the key factors of the interactive signaling transducer,
      fast response, and active interfacial surfaces. The intrinsic features of S-MC
      with different %S-doping (S-MC-1, and S-MC-2) through the sp2-carbon chain create
      abundant catalytic active sites, facilitate molecular diffusion through the
      microporous structure, promote strong binding with the targeted molecules, and
      induce interactions at electrolyte-electrode interfaces. The S-MC-1 provides
      selective signaling in a tertiary mixture of DA, ascorbic acid (AA), and uric
      acid (UA) with a high sensitivity and a wide linear range of 0.01-5, 10-4000, and
      1-2000 uM, respectively. The detection limits were set at 3 nM, 1.26 uM, and 0.23
      uM for DA, AA, and UA respectively. The S-MC-1 demonstrated a selective screening
      of DA released from PC12 cells under a K+ ion- stimulator with high sensitivity
      and promoted high biocompatibility, low cytotoxicity, high stability, and
      reliable reproducibility (%RSD ranged from 1 to 2.7). Our findings indicated that
      the S-MC-1 can be utilized as an in-vitro model for simultaneously monitoring
      extracellular-DA secreted from living cells and sensing mono-bioactive molecules
      in biological samples.

PMID- 29571161
TI  - Disposable electrochemical detection of breast cancer tumour marker CA 15-3 using
      poly(Toluidine Blue) as imprinted polymer receptor.
AB  - In this work, electrically-conducting poly(Toludine Blue) was employed for the
      first time as synthetic receptor film, prepared by Molecular Imprinting
      strategies and using electrochemical methods, for the specific screening of
      breast cancer biomarker Carbohydrate Antigen 15-3 (CA 15-3). The protein
      imprinted poly(Toluidine Blue) film was grown in a pre-formed Toluidine Blue (TB)
      tailed SAM at the AuSPE surface, which greatly enhanced the stability against
      degradation of the Molecular Imprinted Polymer (MIP) film at the electrode
      surface. The MIP receptor film recognition ability towards the protein was
      investigated by fitting data to Freundlich isotherm. The binding affinity (KF)
      obtained for the MIP system was significantly higher (~ 12-fold) to that obtained
      for the NIP system, demonstrating the success of the approach in creating
      imprinted materials that specifically respond to CA 15-3 protein. The incubation
      of the MIP modified electrode with increasing concentration of protein (from 0.10
      U mL-1 to 1000 U mL-1) resulted in a decrease of the ferro/ferricyanide redox
      current. The device displayed linear response from 0.10 U mL-1 to 100 U mL-1 and
      LODs below 0.10 U mL-1 were obtained from calibration curves built in neutral
      buffer and diluted artificial serum, using DPV technique, enabling the detection
      of the protein biomarker at clinically relevant levels. The developed MIP
      biosensor was applied to the determination of CA 15-3 in spiked serum samples
      with satisfactory results. The developed device provides a new strategy for
      sensitive, rapid, simple and cost-effective screening of CA 15-3 biomarker.
      Importantly, the overall approach seems suitable for point-of-care (PoC) use in
      clinical context.

PMID- 29571162
TI  - Facile crosslinking of polythiophenes by polyethylenimine via ester aminolysis
      for selective Cu(II) detection in water.
AB  - Functionalization of pi-conjugated polymers is dispensable for solubilization of
      the rigid and hydrophobic backbones in water. However, polymer aggregation is
      always present and leads to issues with complication and reproducibility in
      spectral properties. Herein, we reported a simple and robust method to make a
      series of conjugated polymer nanostructures by a crosslinking strategy. In favor
      of multivalency effect, polythionenes with various chain lengths were
      functionalized with branched polyethylenimine (PEI) via ester aminolysis reaction
      under mild conditions. Photophysical studies revealed the conjugated backbones
      could be well stabilized and dispersed in water. By taking advantage of
      intermolecular recognition interaction between copper ions and cationic PEI, we
      applied crosslinked polythiophenes as a nano probe at very low concentration
      (0.01 mg/mL) to fluorescently detect copper ions with high sensitivity up to 10
      nM and selectivity over other metal ions in aqueous solutions, without occurrence
      of detectable aggregates. The overall performance of our nano probes outperforms
      reported water-soluble polymers-based probes, particularly in probe availability
      and manipulation as well as selective copper detection capability.

PMID- 29571163
TI  - Performance comparison between multienzymes loaded single and dual electrodes for
      the simultaneous electrochemical detection of adenosine and metabolites in
      cancerous cells.
AB  - The analytical performance of the multi enzymes loaded single electrode sensor
      (SES) and dual electrode sensor (DES) was compared for the detection of adenosine
      and metabolites. The SES was fabricated by covalent binding of tri-enzymes,
      adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine
      oxidase (XO) along with hydrazine (Hyd) onto a functionalized conducting polymer
      [2,2:5,2-terthiophene-3-(p-benzoic acid)] (pTTBA). The enzyme reaction electrode
      in DES was fabricated by covalent binding of ADA and PNP onto pTTBA coated on Au
      nanoparticles. The detection electrode in DES was constructed by covalent binding
      of XO and Hyd onto pTTBA coated on porous Au. Due to the higher amount (3.5
      folds) of the immobilized enzymes and Hyd onto the DES than SES, and the lower
      Michaelis constant (Km) value for DES (28.7 uM) compared to SES (36.1 uM), the
      sensitivity was significantly enhanced for the DES (8.2 folds). The dynamic range
      obtained using DES was from 0.5 nM to 120.0 uM with a detection limit of 1.43 nM
      +/- 0.02, 0.76 nM +/- 0.02, and 0.48 nM +/- 0.01, for adenosine (AD), inosine
      (IN), and hypoxanthine (Hypo) respectively. Further, the DES was coupled with an
      electrochemical potential modulated microchannel for the separation and
      simultaneous detection of AD, IN, and Hypo in an extracellular matrix of
      cancerous (A549) and non-cancerous (Vero) cells. The sensor probe confirms a
      higher basal level of extracellular AD and its metabolites in cancer cells
      compared to normal cells. In addition, the effect of dipyridamole on released
      adenosine in A549 cells was investigated.

PMID- 29571164
TI  - Single-molecule porphyrin-metal ion interaction and sensing application.
AB  - It remains a significant challenge to study the interactions between metal ions
      and porphyrin molecules at single ion level. Here, we constructed a nanopore
      based sensing for label-free and real-time analysis of the interaction between
      Cu2+ and 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TPPS). The results
      demonstrate that emerging electronic signatures of the Cu2+-TPPS complex that is
      completely different form the original free TPPS were observed in the alpha
      hemolysin (alpha-HL) nanopore. Based on the distinctive electronic signal
      patterns between TPPS and Cu2+-TPPS complex, the unique nanopore sensor can
      achieve a highly sensitive detection of Cu2+ in aqueous media. The frequency of
      signature events showed a linear response toward the concentration of Cu2+ in the
      range of 0.03 uM - 1.0 MUM, with a detection limit of 16 nM (S/N = 3). The
      sensing system also exhibited high selectivity against other metal ions, and the
      feasibility of this approach for practical applications was demonstrated with the
      determination of Cu2+ in running water.

PMID- 29571166
TI  - Incidence of female homicide in the Transkei sub-region of South Africa (1993
      2015).
AB  - BACKGROUND: Female homicide is very complex and difficult to research. Xhosa
      women are poor, illiterate and live in a rural area where they are exposed to a
      number of risks to their lives. The previous apartheid regimen broke the fabric
      of the family value system in this region and this came on top of a traditional
      patriarchal view of women as little more than property. Women are most vulnerable
      in this traumatised society. OBJECTIVE: To study the incidence of female homicide
      in the Transkei sub-region of South Africa. METHOD: A record review was
      undertaken of all medico-legal autopsies performed from 1993 to 2015 at Mthatha
      Forensic Pathology Laboratory. RESULTS: In total, 26 972 autopsies were performed
      on victims of unnatural death between 1993 and 2015. Of these, 6091 (22.58%) were
      cases of unnatural death among females. Homicide accounted for 1865 (30.61%) of
      these deaths. The average rate of female homicide during the study period was
      12.5 per 100 000. The rate of homicide decreased from 14.25/100 000 (1993) to
      9.19/100 000 (2015). The average rate of death was 4.93/100 000 as a result of
      the use of firearms, 3.75/100 000 for stab injuries and 3.70/100 000 for blunt
      trauma. The rate of murder was highest (6.55/100 000) in the young age group
      between 11 and 40 years. CONCLUSION: Despite a one and half time decrease in the
      rate of female homicide in the last 23 years (1993-2015) in the Transkei sub
      region of South Africa, it is still three times higher than the worldwide rate.

PMID- 29571165
TI  - Structural model, functional modulation by ivermectin and tissue localization of
      Haemonchus contortus P-glycoprotein-13.
AB  - Haemonchus contortus, one of the most economically important parasites of small
      ruminants, has become resistant to the anthelmintic ivermectin. Deciphering the
      role of P-glycoproteins in ivermectin resistance is desirable for understanding
      and overcoming this resistance. In the model nematode, Caenorhabditis elegans, P
      glycoprotein-13 is expressed in the amphids, important neuronal structures for
      ivermectin activity. We have focused on its ortholog in the parasite, Hco-Pgp-13.
      A 3D model of Hco-Pgp-13, presenting an open inward-facing conformation, has been
      constructed by homology with the Cel-Pgp-1 crystal structure. In silico docking
      calculations predicted high affinity binding of ivermectin and actinomycin D to
      the inner chamber of the protein. Following in vitro expression, we showed that
      ivermectin and actinomycin D modulated Hco-Pgp-13 ATPase activity with high
      affinity. Finally, we found in vivo Hco-Pgp-13 localization in epithelial,
      pharyngeal and neuronal tissues. Taken together, these data suggest a role for
      Hco-Pgp-13 in ivermectin transport, which could contribute to anthelmintic
      resistance.

PMID- 29571167
TI  - The association between type of spine fracture and the mechanism of trauma: A
      useful tool for identifying mechanism of trauma on legal medicine field.
AB  - BACKGROUND: Determining the association between mechanism of trauma, and the type
      of spine column fracture is a useful approach for exactly describing spine injury
      on forensic medicine field. We aimed to determine mechanism of trauma based on
      distribution of the transition of spinal column fractures. METHODS: This cross
      sectional survey was performed on 117 consecutive patients with the history of
      spinal trauma who were admitted to emergency ward of Rasoul-e-Akram Hospital in
      Tehran, Iran from April 2015 to March 2016. The baseline characteristics were
      collected by reviewing the hospital recorded files. RESULTS: With respect to
      mechanism of fracture, 63.2% of fractures were caused by falling, 30.8% by
      collisions with motor vehicles, and others caused by the violence. Regarding site
      of fracture, lumbosacral was affected in 47.9%, thoracic in 29.9%, and cervical
      in 13.7%. Regarding type of fracture, burst fracture was the most common type
      (71.8%) followed by compressive fracture (14.5%). The site of fracture was
      specifically associated with the mechanism of injury; the most common injuries
      induced by falling from height were found in lumbosacral and cervical sites, and
      the most frequent injuries by traffic accidents were found in thoracic site; also
      the injuries following violence were observed more in lumbar vertebrae. The burst
      fractures were more revealed in the patients affected by falling from height and
      by traffic accidents, and both burst and compressive fractures were more observed
      with the same result in the patients injured with violence (p = 0.003).
      CONCLUSION: The type of spine fracture due to trauma is closely associated with
      the mechanism of trauma that can be helpful in legal medicine to identify the
      mechanism of trauma in affected patients.

PMID- 29571168
TI  - Two-phase high solid anaerobic digestion with dewatered sludge: Improved volatile
      solid degradation and specific methane generation by temperature and pH
      regulation.
AB  - The effects of temperature and pH on volatile solid (VS) degradation and CH4
      production of anaerobic digestion treating high-solid municipal dewatered sludge
      was studied. There were two single-phase reactors in Group 1: 35 and 55  degrees
      C reactors. In Group 2 (G2), acidification phase temperature was 55  degrees C or
      70  degrees C and digestion phase temperature was 35  degrees C or 55  degrees C.
      G3 was set on the basis of G2 with the initial pH adjusted to 10.0. VS
      degradation ratio and CH4 generation ratio of G2 and G3 were higher than G1. In
      G2, acidification reactors did not show much difference on VS degradation and CH4
      generation. Higher VS degradation ratio with higher CH4 generation ratio was get
      in extreme thermophilic/thermophilic-mesophilic systems. In G3, pH adjustment
      only promoted VS degradation and CH4 generation in acidification reactors when
      compared to G2, but the two ratios of the whole systems was not further enhanced.

PMID- 29571169
TI  - Cake layer bacterial communities during different biofouling stages in full-scale
      membrane bioreactors.
AB  - A detailed understanding of the bacterial communities in the cake layers formed
      on the membrane surface is required to control biofouling in a membrane
      bioreactor (MBR). This study aimed to investigate the dynamics of the cake layer
      bacterial communities in full-scale MBRs operated in a wastewater treatment plant
      in Japan and to identify the key bacteria responsible for cake layer formation.
      The bacterial communities in the cake layer and the activated sludge were
      analyzed using 16S rRNA gene amplicon sequencing when biofouling occurred under
      different fouling conditions. The most dominant phyla in activated sludge were
      almost always Proteobacteria and Bacteroidetes. By contrast, when the cake layer
      had unique bacterial communities distinguishable from those in the activated
      sludge, members of Firmicutes were highly dominant in the cake layer,
      irrespective of the fouling conditions. This study reported for the first time
      that Firmicutes play an important role throughout the biofouling process.

PMID- 29571170
TI  - 4-Chlorophenol biodegradation facilitator composed of recombinant multi
      biocatalysts immobilized onto montmorillonite.
AB  - A biodegradation facilitator which catalyzes the initial steps of 4-chlorophenol
      (4-CP) oxidation was prepared by immobilizing multiple enzymes (monooxygenase,
      CphC-I and dioxygenase, CphA-I) onto a natural inorganic support. The enzymes
      were obtained via overexpression and purification after cloning the corresponding
      genes (cphC-I and cphA-I) from Arthrobacter chlorophenolicus A6. Then, the
      recombinant CphC-I was immobilized onto fulvic acid-activated montmorillonite.
      The immobilization yield was 60%, and the high enzyme activity (82.6%) was
      retained after immobilization. Kinetic analysis indicated that the Michaelis
      Menten model parameters for the immobilized CphC-I were similar to those for the
      free enzyme. The enzyme stability was markedly enhanced after immobilization. The
      immobilized enzyme exhibited a high level of activity even after repetitive use
      (84.7%) and powdering (65.8%). 4-CP was sequentially oxidized by a multiple
      enzyme complex, comprising the immobilized CphC-I and CphA-I, via the
      hydroquinone pathway: oxidative transformation of 4-CP to hydroxyquinol followed
      by ring fission of hydroxyquinol.

PMID- 29571171
TI  - Mixing effects on the kinetics and the dynamics of two-phase enzymatic hydrolysis
      of hemicellulose for biofuel production.
AB  - This work uses a coupled experimental and modeling approach to explore the
      effects of macro- and micro-mixing on the kinetics and the dynamics of two-phase
      enzymatic hydrolysis of hemicellulose. Reactor mixing does not alter the non
      competitive nature of product inhibition in hemicellulose hydrolysis by
      endoxylanase, but produces stronger inhibition that reduces the soluble sugar
      yield by 8-14.5%, as the mixing speed increases from 0 to 200 rpm. The kinetic
      constants (Km, Vmax, Kx) assume mass-transfer disguised values at 0-200 rpm. An
      optimal mixing strategy, comprising of 55-70 min of initial rapid convective
      macromixing followed by diffusive micromixing (without any macromixing) for the
      rest of the hydrolysis, increases xylose and reducing sugar yields by 6.3-8% and
      13-20%, respectively, over continuous mixing at 200 rpm, for 1-5 mg/ml substrate
      loading at an optimum enzyme to substrate ratio of 1:20, with an energy saving of
      94-96% over 24 h.

PMID- 29571172
TI  - Management of high-risk breast lesions found on mammogram or ultrasound: the
      value of contrast-enhanced MRI to exclude malignancy.
AB  - PURPOSE: To evaluate the performance of magnetic resonance imaging (MRI) to
      exclude malignancy in biopsy-proven high-risk breast lesions prior to surgical
      excision. MATERIAL AND METHODS: Breast MRIs performed after a core needle biopsy
      (CNB) yielding high-risk pathology were evaluated for the presence of suspicious
      enhancement. The diagnostic performance of MRI to exclude malignancy was
      calculated. RESULTS: The average reader sensitivity, specificity, negative
      predictive value, positive predictive value and accuracy of MRI were 92%, 51%,
      98%, 22% and 56%, respectively. CONCLUSION: Lack of enhancement on MRI at the
      site of a high-risk lesion was useful for excluding malignancy.

PMID- 29571173
TI  - Seizure Freedom in Patients with Dravet Syndrome with Contraceptives: A Case
      Report with Two Patients.
AB  - Dravet syndrome is a rare and malignant epileptic syndrome that is typically
      resistant to antiepileptic drugs. There is a growing interest in the
      antiepileptic properties of neurosteroids. Especially progesterone is known to
      act as an anticonvulsive agent. However, contraceptives that act as orally given
      neurosteroids often lead to increased seizures in women with epilepsy.We report
      on two girls with Dravet syndrome, who gained seizure freedom under therapy with
      contraceptives. The first patient received an oral contraceptive, a combination
      of an estrogen, and a gestagen, due to hypermenorrhea. The second received a pure
      gestagen implant for contraception.The antiepileptic effect of progesterone is
      mainly attributed to its conversion into allopregnanolone and related
      neurosteroids, which are positive modulators of gamma-aminobutyric acid A
      receptors. It is unclear whether the observed effect of these contraceptives
      containing synthetic progesterone derivatives may be specific for the Dravet
      syndrome, and it is unclear whether and how this observation can be used
      therapeutically.

PMID- 29571174
TI  - Integration of Biochemometrics and Molecular Networking to Identify
      Antimicrobials in Angelica keiskei.
AB  - Botanical medicines have been utilized for centuries, but it remains challenging
      to identify bioactive constituents from complex botanical extracts. Bioassay
      guided fractionation is often biased toward abundant or easily isolatable
      compounds. To comprehensively evaluate active botanical mixtures, methods that
      allow for the prioritization of active compounds are needed. To this end, a
      method integrating bioassay-guided fractionation, biochemometric selectivity
      ratio analysis, and molecular networking was devised and applied to Angelica
      keiskei to comprehensively evaluate its antimicrobial activity against
      Staphylococcus aureus. This approach enabled the identification of putative
      active constituents early in the fractionation process and provided structural
      information for these compounds. A subset of chalcone analogs were prioritized
      for isolation, yielding 4-hydroxyderricin (1, minimal inhibitory concentration
      [MIC] <= 4.6 uM, IC50 = 2.0 uM), xanthoangelol (2, MIC <= 4.0 uM, IC50 = 2.3) and
      xanthoangelol K (4, IC50 = 168 uM). This approach allowed for the identification
      of a low-abundance compound (xanthoangelol K) that has not been previously
      reported to possess antimicrobial activity and facilitated a more comprehensive
      understanding of the compounds responsible for A. keiskei's antimicrobial
      activity.

PMID- 29571175
TI  - Development and validation of the SIMPLE endoscopic classification of diminutive
      and small colorectal polyps.
AB  - BACKGROUND: Prediction of histology of small polyps facilitates colonoscopic
      treatment. The aims of this study were: 1) to develop a simplified polyp
      classification, 2) to evaluate its performance in predicting polyp histology, and
      3) to evaluate the reproducibility of the classification by trainees using
      multiplatform endoscopic systems. METHODS: In phase 1, a new simplified
      endoscopic classification for polyps - Simplified Identification Method for Polyp
      Labeling during Endoscopy (SIMPLE) - was created, using the new I-SCAN OE system
      (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy,
      level of confidence, and interobserver agreement to predict polyp histology
      before and after training, and univariable/multivariable analysis of the
      endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by
      trainees using different endoscopy platforms was evaluated. RESULTS: Using the
      SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95
      % confidence interval [CI] 77 % - 88 %) before and 94 % (95 %CI 89 % - 97 %)
      after training (P  = 0.002). The sensitivity, specificity, positive predictive
      value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91
      %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30
      - 0.64) before to 0.66 (95 %CI 0.48 - 0.82) after training. The trainees
      demonstrated that the SIMPLE classification is applicable across endoscopy
      platforms, with similar post-training accuracies for narrow-band imaging NBI
      classification (0.69; 95 %CI 0.64 - 0.73) and SIMPLE (0.71; 95 %CI 0.67 - 0.75).
      CONCLUSIONS: Using the I-SCAN OE system, the new SIMPLE classification
      demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE
      PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN
      OE or NBI.

PMID- 29571177
TI  - Large In-mask Motion during Frameless Radiosurgery of a Brain Metastasis.
AB  - Frameless radiosurgery is now a common alternative to traditional in-frame
      treatment. Several dosimetric studies have reported small in-mask positioning
      inaccuracies during frameless radiosurgery. We present a case of an uncommonly
      large deviation in in-mask motion detected offline in a patient undergoing linear
      accelerator-based frameless radiosurgery. Our case illustrates how the use of a
      thermoplastic mask can lead to unacceptable setup errors for passive image-guided
      radiosurgery. The case underlines the need for correct patient preparation,
      adequate time between mask molding and computed tomography, and routine
      intrafraction imaging. Image-guided positioning is recommended to achieve
      clinically acceptable setup accuracy (< 1 mm) for stereotactic radiosurgery.

PMID- 29571176
TI  - Intraoperative Ultrasound Appearance of a Pancreatic Cerebral Metastasis: A Case
      Report.
AB  - BACKGROUND:  Brain metastases (BMs) derived from pancreatic adenocarcinoma (PAC)
      have an extremely low incidence (0.1-0.4%) and are usually associated with a very
      poor prognosis. The treatment strategy is palliative and includes conventional
      radiotherapy, stereotactic radiosurgery, chemotherapy, and surgical resection.
      CASE DESCRIPTION:  A 39-year-old man with a history of PAC developed a systemic
      tumor relapse with intracranial progression. Magnetic resonance imaging (MRI)
      documented a right rolandic, cortical, and cystic lesion with leptomeningeal
      intrasulcular extension. The intraoperative ultrasound (iUS) depicted a
      hyperechogenic area surrounding the anechogenic cystic lesion and allowed us to
      obtain gross total resection of the tumor. CONCLUSIONS:  To the best of our
      knowledge, we describe for the first time the iUS aspect of a pancreatic BM. In
      this case the use of iUS allowed us to increase the extent of resection and
      surgical safety, thus reducing the risk of new postoperative neurologic deficits.

PMID- 29571178
TI  - ?

PMID- 29571179
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PMID- 29571196
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PMID- 29571197
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PMID- 29571199
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PMID- 29571198
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PMID- 29571200
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PMID- 29571201
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PMID- 29571202
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PMID- 29571203
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PMID- 29571204
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PMID- 29571206
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PMID- 29571205
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PMID- 29571207
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PMID- 29571208
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PMID- 29571210
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PMID- 29571209
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PMID- 29571211
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PMID- 29571213
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PMID- 29571214
TI  - High-Performance Additive-/Post-Treatment-Free Nonfullerene Polymer Solar Cells
      via Tuning Molecular Weight of Conjugated Polymers.
AB  - In recent years, rapid advances are achieved in polymer solar cells (PSCs) using
      nonfullerene small molecular acceptors. However, no research disclosing the
      influence of molecular weight (Mn ) of conjugated polymer on the nonfullerene
      device performance is reported. In this work, a series of polymers with different
      Mn s are synthesized to systematically investigate the connection between Mn and
      performance of nonfullerene devices for the first time. It is found that the
      device performance improves substantially as the Mn increases from 12 to 38 kDa
      and a power conversion efficiency (PCE) as high as 10.5% is realized. It has to
      be noted this PCE is achieved without using any additives and post-treatments,
      which is among the top efficiencies of additive- and post-treatment-free PSCs.
      Most importantly, the variation trend of the optimal active layer thickness and
      morphology is significantly different from the device with fullerene as acceptor.
      The findings clarify the effect of Mn on the performance of nonfullerene PSCs,
      which would benefit further efficiency improvement of nonfullerene PSCs.

PMID- 29571215
TI  - Molybdenum Carbide-Decorated Metallic Cobalt@Nitrogen-Doped Carbon Polyhedrons
      for Enhanced Electrocatalytic Hydrogen Evolution.
AB  - Electrocatalytic hydrogen evolution reaction (HER) based on water splitting holds
      great promise for clean energy technologies, in which the key issue is exploring
      cost-effective materials to replace noble metal catalysts. Here, a sequential
      chemical etching and pyrolysis strategy are developed to prepare molybdenum
      carbide-decorated metallic cobalt@nitrogen-doped porous carbon polyhedrons
      (denoted as Mo/Co@N-C) hybrids for enhanced electrocatalytic hydrogen evolution.
      The obtained metallic Co nanoparticles are coated by N-doped carbon thin layers
      while the formed molybdenum carbide nanoparticles are well-dispersed in the whole
      Co@N-C frames. Benefiting from the additionally implanted molybdenum carbide
      active sites, the HER performance of Mo/Co@N-C hybrids is significantly promoted
      compared with the single Co@N-C that is derived from the pristine ZIF-67 both in
      alkaline and acidic media. As a result, the as-synthesized Mo/Co@N-C hybrids
      exhibit superior HER electrocatalytic activity, and only very low overpotentials
      of 157 and 187 mV are needed at 10 mA cm-2 in 1 m KOH and 0.5 m H2 SO4 ,
      respectively, opening a door for rational design and fabrication of novel low
      cost electrocatalysts with hierarchical structures toward electrochemical energy
      storage and conversion.

PMID- 29571216
TI  - Metal-Ion-Mediated Supramolecular Chirality of l-Phenylalanine Based Hydrogels.
AB  - For chiral hydrogels and related applications, one of the critical issues is how
      to control the chirality of supramolecular systems in an efficient way, including
      easy operation, efficient transfer of chirality, and so on. Herein,
      supramolecular chirality of l-phenylalanine based hydrogels can be effectively
      controlled by using a broad range of metal ions. The degree of twisting (twist
      pitch) and the diameter of the chiral nanostructures can also be efficiently
      regulated. These are ascribed to the synergic effect of hydrogen bonding and
      metal ion coordination. This study may develop a method to design a new class of
      electronically, optically, and biologically active materials.

PMID- 29571217
TI  - Chemistry of Metallacyclobutadienes.
AB  - Metallacyclobutadienes are analogues of cyclobutadienes in which one of the
      cyclobutadiene CR groups has been formally replaced by a transition-metal
      fragment. These metallacycles are interesting because they can play an important
      role in catalysis and can serve as starting materials for the syntheses of
      organometallic compounds such as metallabenzene, eta5 -cyclopentadienyl, and eta3
      -cyclopropenyl complexes. Unlike cyclobutadienes, metallacyclobutadienes can be
      significantly more stable. A number of metallacyclobutadienes have now been
      isolated and thoroughly characterized, especially for those that contain
      transition metals of groups 5-9. Their properties have also been actively
      investigated. This article highlights the chemistry of metallacyclobutadienes
      with reference to their syntheses, reactivity, and structural properties.

PMID- 29571218
TI  - Concerted Catalysis by Adjacent Palladium and Gold in Alloy Nanoparticles for the
      Versatile and Practical [2+2+2] Cycloaddition of Alkynes.
AB  - A Pd-Au alloy efficiently catalyzed the [2+2+2] cycloaddition of substituted
      alkynes. Whereas monometallic Pd and Au catalysts were totally ineffective, Pd-Au
      alloy nanoparticle catalysts with a low Pd/Au molar ratio showed high activity to
      give the corresponding polysubstituted arenes in high yields. A variety of
      substituted alkynes participated in various modes of cycloaddition under Pd-Au
      alloy catalysis. The Pd-Au alloy catalysts exhibited high air tolerance and
      reusability.

PMID- 29571219
TI  - Plasticity of mycangia in Xylosandrus ambrosia beetles.
AB  - Insects that depend on microbial mutualists evolved a variety of organs to
      transport the microsymbionts while dispersing. The ontogeny and variability of
      such organs is rarely studied, and the microsymbiont's effects on the animal
      tissue development remain unknown in most cases. Ambrosia beetles (Coleoptera:
      Curculionidae: Scolytinae or Platypodinae) and their mutualistic fungi are an
      ideal system to study the animal-fungus interactions. While the interspecific
      diversity of their fungus transport organ-mycangia-is well-known, their
      developmental plasticity has been poorly described. To determine the ontogeny of
      the mycangium and the influence of the symbiotic fungus on the tissue
      development, we dissected by hand or scanned with micro-CT the mycangia in
      various developmental stages in five Xylosandrus ambrosia beetle species that
      possess a large, mesonotal mycangium: Xylosandrus amputatus, Xylosandrus
      compactus, Xylosandrus crassiusculus, Xylosandrus discolor, and Xylosandrus
      germanus. We processed 181 beetle samples from the United States and China. All
      five species displayed three stages of the mycangium development: (1) young
      teneral adults had an empty, deflated and cryptic mycangium without fungal mass;
      (2) in fully mature adults during dispersal, the pro-mesonotal membrane was
      inflated, and most individuals developed a mycangium mostly filled with the
      symbiont, though size and symmetry varied; and (3) after successful establishment
      of their new galleries, most females discharged the bulk of the fungal inoculum
      and deflated the mycangium. Experimental aposymbiotic individuals demonstrated
      that the pronotal membrane invaginated independently of the presence of the
      fungus, but the fungus was required for inflation. Mycangia are more dynamic than
      previously thought, and their morphological changes correspond to the phases of
      the symbiosis. Importantly, studies of the fungal symbionts or plant pathogen
      transmission in ambrosia beetles need to consider which developmental stage to
      sample. We provide illustrations of the different stages, including
      microphotography of dissections and micro-CT scans.

PMID- 29571220
TI  - Shaping nursing profession regulation through history - a systematic review.
AB  - AIM: The aim of this systematic review was to provide a critical synthesis of the
      factors that historically shaped the advancements of nursing regulators
      worldwide. BACKGROUND: An in-depth examination of the different factors that
      moulded regulatory changes over time is pivotal to comprehend current issues in
      nursing. INTRODUCTION: In the light of global health scenarios, the researchers
      explored the factors that historically influenced the socio-contextual
      circumstances upon which governments made regulatory changes. METHODS: A
      systematic search was performed on the following databases: PubMed, CINAHL,
      Scopus, OpenGrey and ScienceDirect. The review included papers from January 2000
      to October 2016 published in English. The authors used the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) and an inductive thematic
      approach for synthesis. RESULTS: Two main themes were identified: factors
      underpinning current challenges and historical and contextual triggers of
      regulation. The first theme was composed of three aspects: education, migration
      and internationalization, and policy and regulation; the second theme consisted
      of four attributes: demographics, economics, history of registration and wars,
      and historical changes in nursing practice. DISCUSSION: Factors that shaped
      nursing regulation were linked to changing demographics and economics, education,
      history of nursing registration, shifting patterns of migration and
      internationalization, nursing practice, policy and regulation and significant
      societal turns often prompted by wars. CONCLUSION: A deeper understanding of the
      developments of the nursing regulatory institutions provides the foundation for
      portable standards that can be applied across an array of jurisdictions to
      guarantee a better public safety. IMPLICATION FOR NURSING AND HEALTH POLICY:
      Understanding factors that socially, legislatively and politically have
      influenced the development of regulatory bodies over time helps to mould local,
      national and international policies that have a stronger impact on health
      worldwide. To achieve this, there must be effective cooperation among systems of
      nursing regulations globally.

PMID- 29571221
TI  - The impact of simulation education on self-efficacy towards teaching for nurse
      educators.
AB  - AIM: The objective of this study was to assess the impact of a simulation
      workshop on self-efficacy towards teaching for nurse educators in India.
      Additionally, we sought to revise and validate a tool to measure self-efficacy in
      teaching for use with a global audience. BACKGROUND: Simulation is an evidence
      based teaching and learning method and is increasingly used in nursing education
      globally. INTRODUCTION: As new technology and teaching methods such as simulation
      continue to evolve, it is important for new as well as experienced nurse
      educators globally to have confidence in their teaching skills and abilities.
      METHODS: The study included (1) instrument revision, and measures of reliability
      and validation, (2) an 8-h faculty development workshop intervention on
      simulation, (3) pre- and post-survey of self-efficacy among nurse educators, and
      (4) investigation of relationship between faculty socio-demographics and degree
      of self-efficacy. RESULTS: The modified tool showed internal consistency (r =
      0.98) and was validated by international faculty experts. There were significant
      improvements in total self-efficacy (P < 0.001) and subscale scores among nurse
      educators after the simulation workshop intervention when compared to pre-survey
      results. No significant relationships were found between socio-demographic
      variables and degree of self-efficacy. DISCUSSION: Strong self-efficacy in
      teaching among nurse educators is crucial for effective learning to occur.
      CONCLUSIONS AND IMPLICATIONS FOR NURSING: Results indicated the simulation
      workshop was effective in significantly improving self-efficacy towards teaching
      for nurse educators using an internationally validated tool. IMPLICATIONS FOR
      NURSING POLICY: The Minister of Health in India recently called for improvements
      in nursing education. Introducing nursing education on simulation as a teaching
      method in India and globally to improve self-efficacy among teachers is an
      example of a strategy towards meeting this call.

PMID- 29571222
TI  - Defect Engineering in Few-Layer Phosphorene.
AB  - Defect engineering in 2D phosphorene samples is becoming an important and
      powerful technique to alter their properties, enabling new optoelectronic
      applications, particularly at the infrared wavelength region. Defect engineering
      in a few-layer phosphorene sample via introduction of substrate trapping centers
      is realized. In a three-layer (3L) phosphorene sample, a strong photoluminescence
      (PL) emission peak from localized excitons at ~1430 nm is observed, a much lower
      energy level than free excitonic emissions. An activation energy of ~77 meV for
      the localized excitons is determined in temperature-dependent PL measurements.
      The relatively high activation energy supports the strong stability of the
      localized excitons even at elevated temperature. The quantum efficiency of
      localized exciton emission in 3L phosphorene is measured to be approximately
      three times higher than that of free excitons. These results could enable
      exciting applications in infrared optoelectronics.

PMID- 29571223
TI  - Work values and their association with burnout/work engagement among nurses in
      long-term care hospitals.
AB  - AIMS: To examine burnout and work engagement among nurses in Japanese long-term
      care hospitals and their relation to nurses' and organisational work values, and
      nurse-organisation congruence of such values. BACKGROUND: Nursing managers must
      help improve nurses' well-being; however, no research has considered strategies
      to improve staff outcomes in long-term care hospitals. We propose that individual
      nurse's work values and the congruence of these values with those of their
      organisations may influence burnout and work engagement. METHODS: We conducted a
      cross-sectional survey of nurses in long-term care hospitals. Multiple regression
      analyses were conducted to examine the effects of nurses' work values and nurse
      organisation congruence in these values on burnout and work engagement. RESULTS:
      Higher individual intrinsic and altruistic work values were associated with
      improvements in nurses' burnout and work engagement. Nurse-organisation non
      congruence in altruistic values was associated with lower work engagement,
      whereas that of intrinsic work values was not associated with either outcome
      variable. CONCLUSION: Promoting intrinsic and altruistic work values among nurses
      could be effective for improving both burnout and work engagement. IMPLICATIONS
      FOR NURSING MANAGEMENT: Opportunities such as case conferences could foster
      intrinsic and altruistic work values through the review of good care practices
      and communication between managers/colleagues about feelings and thoughts.

PMID- 29571224
TI  - Direct IR Spectroscopic Detection of a Low-Lying Electronic State in a Metal
      Carbide Cluster.
AB  - The electronic structure of metal clusters is notoriously difficult to detect
      spectroscopically, due to rapid relaxation into the ground state following
      excitation. We have used IR multiple photon excitation to identify a low-lying
      electronic state in a tantalum carbide cluster. The electronic excitation is
      found at 458 cm-1 , and is confirmed by experiments on isotopically labeled
      clusters. Time-dependent density functional theory (TD-DFT) calculations confirm
      the current assignment, but a second predicted electronic state was not observed.

PMID- 29571226
TI  - The Hyperbaric Oxygen Therapy Registry: Driving quality and demonstrating
      compliance.
AB  - Objective: To provide an update on the status of provider participation in the US
      Wound Registry (USWR) and its specialty registry the Hyperbaric Oxygen Therapy
      Registry (HBOTR), which provide much-needed national benchmarking and quality
      measurement services for hyperbaric medicine. Methods: Providers can meet many
      requirements of the Merit-Based Incentive Payment System (MIPS) and
      simultaneously participate in the HBOTR by transmitting Continuity of Care
      Documents (CCDs) directly from their certified electronic health record (EHR) or
      by reporting hyperbaric quality measures, the specifications for which are
      available free of charge for download from the registry website as electronic
      clinical quality measures for installation into any certified EHR. Computerized
      systems parse the structured data transmitted to the USWR. Patients undergoing
      hyperbaric oxygen (HBO2) therapy are allocated to the HBOTR and stored in that
      specialty registry database. The data can be queried for benchmarking, quality
      reporting, public policy, or specialized data projects. Results: Since January
      2012, 917,758 clinic visits have captured the data of 199,158 patients in the
      USWR, 3,697 of whom underwent HBO2 therapy. Among 27,404 patients with 62,843
      diabetic foot ulcers (DFUs) captured, 9,908 DFUs (15.7%) were treated with HBO2
      therapy. Between January 2016 and September 2018, the benchmark rate for the
      1,000 DFUs treated with HBO2 was 7.3%, with an average of 28 treatments per
      patient. There are 2,100 providers who report data to the USWR by transmitting
      CCDs from their EHR and 688 who submit quality measure data, 300 (43.6%) of whom
      transmit HBO2 quality data.

PMID- 29571227
TI  - Impact of hyperbaric oxygenation on oxidative stress in diabetic patients.
AB  - Taking into consideration that a high concentration of oxygen can express toxic
      effects due to production of reactive oxygen species (ROS), the aim of our
      investigation was to establish the influence of hyperbaric oxygenation on
      oxidative stress parameters and antioxidant enzymes in patients with diabetes
      mellitus (DM) type 2. Investigation included 50 patients with DM type 2 divided
      into two groups. The first group consisted of 25 patients, mean age 70 years,
      mean duration of illness 12 years and without manifest peripheral vascular
      complications (Wagner 0). The second group consisted of 25 patients, mean age 74
      years, mean duration of illness 17 years and with manifest peripheral vascular
      complications (Wagner 1-5). All patients underwent the same therapeutic protocol,
      which included 10 hyperbaric oxygenation therapies, once a day for a duration of
      60 minutes, with an average partial oxygen pressure of 1.7 atmospheres absolute
      (ATA). In blood samples the following parameters of redox balance were
      determined: levels of nitrites (NO2-), index of lipid peroxidation (TBARS),
      superoxide anion radical (O2-), hydrogen peroxide (H2O2) and antioxidant enzymes
      superoxide dismutase (SOD) and catalase (CAT). Our results clearly show that
      hyperbaric oxygen (HBO2) therapy does not have a pro-oxidative effect.
      Additionally, it seems that this procedure strongly mobilized the antioxidant
      enzyme system, thus improving defense from oxidative damage. All significant data
      are marked as P ?0.05. Our results have shown that in terms of ROS production,
      HBO2 can be safe to use in patients suffering from DM type 2 with or without
      vascular complications.

PMID- 29571225
TI  - Folic acid delays development of atherosclerosis in low-density lipoprotein
      receptor-deficient mice.
AB  - Many studies support the cardioprotective effects of folic acid (FA). We aimed to
      evaluate the utility of FA supplementation in preventing the development of
      atherosclerotic in low-density lipoprotein receptor-deficient (LDLR-/-) mice and
      to elucidate the molecular processes underlying this effect. LDLR-/- mice were
      randomly distributed into four groups: control group, HF group, HF + FA group and
      the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the
      following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA +
      RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were
      measured. Atherosclerosis severity was evaluated with oil red O staining.
      Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis
      progression. Immunohistochemical staining was performed with antismooth muscle
      alpha-actin (alpha-SMA) antibodies and anti-osteopontin (OPN) antibodies that
      demonstrate VSMC dedifferentiation. The protein expression of alpha-SMA, OPN and
      mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western
      blot analysis. FA and rapamycin reduced serum levels of total cholesterol,
      triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response.
      Oil red O and H&E staining demonstrated that FA and rapamycin inhibited
      atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in
      vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling
      pathway. Our findings suggest that FA attenuates atherosclerosis development and
      inhibits VSMC dedifferentiation in high-fat-fed LDLR-/- mice by reduced lipid
      levels and inhibiting oxidative stress and the inflammatory response through
      mTOR/p70S6K signalling pathway.

PMID- 29571228
TI  - An anti-barotrauma system for preventing barotrauma during hyperbaric oxygen
      therapy.
AB  - In the present study, a tympanometry-based anti-barotrauma (ABT) device was
      designed using eardrum admittance measurements to develop an objective method of
      preventing barotrauma that occurs during hyperbaric oxygen (HBO2) therapy. The
      middle ear space requires active equalization, and barotrauma of these tissues
      during HBO2therapy constitutes the most common treatment-associated injury.
      Decongestant nasal sprays and nasal steroids are used, but their efficacy is
      questionable to prevent middle ear barotrauma (MEB) during HBO2 treatment.
      Accordingly, a tympanometry-based ABT device was designed using eardrum
      admittance measurements to develop an objective method for preventing MEB, which
      causes pain and injury, and represents one of the principal reasons for patients
      to stop treatment. This study was conducted to test a novel technology that can
      be used to measure transmembrane pressures, and provide chamber attendants with
      real-time feedback regarding the patient's equalization status prior to the onset
      of pain or injury. Eardrum admittance values were measured according to pressure
      changes inside a hyperbaric oxygen chamber while the system was fitted to the
      subject. When the pressure increased to above 200 daPa, eardrum admittance
      decreased to 16.255% of prepressurization levels. After pressure equalization was
      achieved, eardrum admittance recovered to 95.595% of prepressurization levels. A
      one-way repeated measures analysis of variance contrast test was performed on
      eardrum admittance before pressurization versus during pressurization, and before
      pressurization versus after pressure equalization. The analysis revealed
      significant differences at all points during pressurization (P?0.001), but no
      significant difference after pressure equalization was achieved. This ABT device
      can provide objective feedback reflecting eardrum condition to the patient and
      the chamber operator during HBO2 therapy.

PMID- 29571229
TI  - Hyperbaric oxygen therapy as adjuvant for treating wound complications after
      extensive resection for vulvar malignancy.
AB  - Introduction: Necrosis, wound breakdown, and infection represent major
      complications associated with radical vulvectomy. We aimed to analyze the
      feasibility of hyperbaric oxygen (HBO2) therapy as an adjunctive treatment for
      such complications. Methods: We performed a retrospective analysis of the medical
      records, clinical charts, and operative records of vulvar cancer patients who
      underwent hyperbaric oxygen therapy after extensive surgical resection in our
      institute between 2012 and 2016, with a comparison of the clinical outcomes of
      patients with similar surgical procedures andsevere wound complications who did
      not undergo HBO2. Results: A total of 16 patients were included in the study. In
      the subgroup treated with HBO2, seven patients were identified. Two patients had
      primary surgery, while five had recurrent surgery (of these, two had previously
      undergone radiation therapy). Six patients received reconstructive flaps (five
      myocutaneous and onefasciocutaneous), while one patient had primary suture.
      Dehiscence, ischemia and necrosis were estimated to cover 30%-80% of the surgical
      surface area. Surgical debridement was performed in six patients. Daily 90-minute
      sessions in the hyperbaric chamber were performed at a pressure of 2.2
      atmospheres absolute, with partial oxygen pressure of 1672 mbar. Infection
      control and satisfactory healing were achieved using 10-61 sessions. All patients
      in the subgroup who did not receive HBO2 required surgical debridement due to
      partial or near-total flap necrosis, with two reconstructive interventions
      required. Conclusions: Hyperbaric oxygen therapy was an efficient adjuvant for
      wound healing and infection control in managing wound complications after
      extensive vulvar resections.

PMID- 29571230
TI  - Analysis of factors related to failure in the pressure test: a six-year
      experience in Taiwan.
AB  - Introduction: The Republic of China Navy instituted the pressure test as one of
      the selection tools for diving troops and submarine crews. We analyzed factors
      associated with failure in the pressure test. Methods: This was a retrospective
      cohort study designed to investigate pressure test failure in Navy recruits
      between January 2010 and August 2015. The recruits received pressurization in a
      hyperbaric chamber to a simulated depth of 112 feet of seawater (fsw) at a rate
      of 25 fsw/minute. Data describing trainee demographics, disease history, causes
      and depth of failure, as well as type of injury, were extracted from case notes
      and facility databases for statistical analysis. Results: Of 3,608 trial cohorts,
      there were 435 failures, with an overall failure rate of 12.06%. About 95% of
      these failure trials were within a simulated depth of 60 fsw. Fifty-seven (57)
      failures did not record causes of failure. Among the other 378 failures, the most
      commonly identified causes were ear barotrauma (365 trials, 96.56%) and sinus
      barotrauma (10 trials, 2.65%). Statistical analysis revealed that recent upper
      respiratory tract infection, allergic rhinitis, and cigarette smoking were all
      significantly associated with higher incidence of middle ear barotrauma.
      Conclusions: Our results suggest that pressure testing to a depth of 60 fsw is
      effective in disqualifying personnel entering diving and submarine service.
      Recent infection of the upper respiratory tract, allergic rhinitis and cigarette
      smoking are risk factors for middle ear barotrauma, resulting in failure of the
      pressure test.

PMID- 29571231
TI  - A case-control questionnaire survey of decompression sickness risk in Okinawa
      divers.
AB  - Background: Decompression sickness (DCS) is a rare condition that is often
      difficult to diagnose in deep-sea divers. Because of this, prevention and early
      diagnosis are important. In this case-control study, we examined the risk and
      preventive factors associated with DCS. Methods: Our original questionnaire
      survey was conducted among 269 recreational divers in Okinawa. Divers who were
      diagnosed with DCS by a physician (n = 94) were compared with healthy
      recreational divers (n = 175). The questionnaire consisted of 30 items and
      included a dive profile. Odds ratios and multiple logistic regression analysis
      were used to estimate the relative risk of DCS. Results: Logistic regression
      analysis revealed the following risk factors for DCS: a past history of DCS,
      drinking alcohol the evening before diving, indicating decompression stops, cold
      exposure after the dive, and maximum depth. Preventive factors included hydration
      before the dive, deep stops, safety stops and using nitrox gas. The results were
      reliable according to the Hosmer-Lemeshow and omnibus tests. Conclusion: We
      identified certain risk factors, together with their relative risks, for DCS.
      These risk factors may facilitate prevention of DCS among Okinawa divers.

PMID- 29571232
TI  - Influence of exposure in hyperbaric chambers on selected parametersof oxidative
      stress in professional divers.
AB  - Purpose: This study evaluated the influence of hyperbaric exposure chambers on
      selected parameters of oxidative stress in divers' blood. Methods: 25 healthy men
      (non-smoking experienced divers) ages 18-40 took part in the experiment. Subjects
      were exposed to hyperbaric conditions similar to those at 30 meters of depth
      while diving. A control group consisted of 20 healthy men who have never dived or
      been exposed to hyperbaric conditions. Blood was drawn from the cubital vein
      after overnight fasting. Superoxide dismutase (SOD-1) activity and
      malondialdehyde (MDA) concentration were marked in red blood cells (RBCs),
      carbonyl group concentration marked in serum proteins, and nitrate/nitrite
      concentrations were estimated in plasma. Results: Statistically significant
      differences were found between the divers and the control group in MDA
      concentration in erythrocytes and carbonyl group concentration in serum proteins.
      Nitrite/nitrate concentrations in plasma plus SOD-1 activity in RBCs decreased
      significantly in the diver group compared with the control group. After
      hyperbaric exposure MDA concentration in erythrocytes increased considerably in
      the test group and a significant increase in SOD-1 activity was observed. A
      significant increase of nitrite/nitrate concentration was noted in plasma as well
      as an increase in the carbonyl group in serum proteins. Conclusion: Considerably
      weak enzymatic antioxidative defense was observed in the RBCs of individuals
      exposed to hyperbaric pressures versus those in normobary. This issue indicates
      that a diver's system has a larger susceptibility for negative effects from
      oxidative stress. The results also indicate that hyperbaric conditions can
      intensify reactions via free radicals.

PMID- 29571233
TI  - Blood lactate accumulation during competitive freediving and synchronized
      swimming.
AB  - A number of competitive water sports are performed while breath-holding (apnea).
      Such performances put large demands on the anaerobic system, but the study of
      lactate accumulation in apneic sports is limited. We therefore aimed to determine
      and compare the net lactate accumulation (NLA) during competition events in six
      disciplines of competitive freediving (FD) and three disciplines of synchronized
      swimming (SSW). The FD disciplines were: static apnea (STA; n = 14); dynamic
      apnea (DYN; n = 19); dynamic apnea no fins (DNF; n = 16); constant weight (CWT; n
      = 12); constant weight no fins (CNF; n = 8); free immersion (FIM; n =10). The SSW
      disciplines were solo (n = 21), duet (n = 31) and team (n = 34). Capillary blood
      lactate concentration was measured before and three minutes after competition
      performances, and apneic duration and performance variables were recorded. In all
      nine disciplines NLA was observed. The highest mean (SD) NLA (mmol.L-1) was found
      in CNF at 6.3 (2.2), followed by CWT at 5.9 (2.3) and SSW solo at 5 (1.9). STA
      showed the lowest NLA 0.7 (0.7) mmol.L-1 compared to all other disciplines (P ?
      0.001). The NLA recorded shows that sports involving apnea involve high levels of
      anaerobic activity. The highest NLA was related to both work done by large muscle
      groups and long apneic periods, suggesting that NLA is influenced by both the
      type of work and apnea duration, with lower NLA in SSW due to shorter apneic
      episodes with intermittent breathing.

PMID- 29571234
TI  - Cervicocranial artery dissection and scuba diving: Is there a link or is it
      serendipity?
AB  - Introduction: Numerous reports have documented cervicocranial artery dissection
      (CCAD) associated with scuba diving. The question remains as to whether there are
      risk factors unique to scuba diving related to the occurrence of CCAD.
      Objectives: This article aims to perform an examination of the reported cases to
      demonstrate any commonality among the injured divers and association with known
      risk factors for CCAD. Methods: A PubMed search was performed utilizing the key
      words: carotid artery dissection, dissection, arterial dissection, cranial artery
      dissection, scuba, diving, scuba diving. Articles including reports, reviews,
      trials, case series, and letters were considered. Each report was critically
      dissected for information specific to the dive itself and the diver and analyzed
      for similarities and consistency with known risks. Results: Twelve (12) reports
      of CCAD associated with scuba diving were identified. Activities involved with
      scuba diving appear to be consistent with CCAD risk factors. It is unclear if
      hyperbaric stress and physiological changes during a dive present specific risk.
      Trauma - e.g., environmental protection and activities associated with diving -
      was identified as a common risk factor in all cases. Ten (10) cases involved
      arteries at anatomic sites commonly associated with dissections. Seven divers
      documented to have dive profiles suspicious of decompression sickness were
      identified. Conclusions: There appears to be a correlation with minor traumas
      that occur with diving and CCAD. The inconsistency of the dive-related specific
      information reported makes it impossible for investigation of hyperbaric stress
      related risk factors for CCAD to be analyzed.

PMID- 29571235
TI  - Do not fear the Framingham: Practical application to properly evaluate and modify
      cardiovascular risk in commercial divers.
AB  - Introduction: In April 2016 the Association of Diving Contractors International
      (ADCI) consensus guidelines began recommending annual cardiovascular risk
      stratification of commercial divers using the Framingham Risk Score (FRS). For
      those at elevated risk, further testing is recommended. This approach has raised
      concerns about potential operational and financial impacts. However, the
      prevalence of elevated cardiovascular risk and need for additional testing among
      commercial divers is not known. Methods: Clinical data required to calculate the
      FRS was abstracted for 190 commercial divers in two cohorts. Population
      demographics, FRS distribution, contributions of risk factors and effect of
      interventions on reducing risk-factor burden were assessed. Results: Mean FRS
      score was 1.68 +/- 6.35 points, with 13 divers (6.8%) at intermediate risk and
      none at high 10-year risk. In these 13 divers, the mean contributions to the FRS
      were from age (6.5 points), cholesterol (3.1 pts.), smoking (1.3 pts.),
      highdensity lipoprotein (1 pt.), and systolic blood pressure (0.8 pts). The
      youngest age group had a significantly higher modifiable risk core than the
      oldest age group (5.87 vs. 1.2 points, P ? 0.001). All 13 intermediate risk
      divers could have been reclassified as low-risk with successful treatment of
      modifiable risk factors. Discussion: The prevalence of elevated cardiovascular
      risk among commercial divers is low, and treatment of modifiable risk factors
      could reclassify those at intermediate risk to low risk. Therefore, FRS
      implementation coupled with intensive risk-reduction strategies for at risk
      divers may help improve diver health and prolong the careers of divers while
      limiting the need for additional testing and adverse operational impact.

PMID- 29571236
TI  - Hyperbaric oxygen for late sequelae of carbon monoxide poisoning enhances
      neurological recovery: case report.
AB  - Neuropsychiatric sequelae have been reported in 15%-45% of survivors of carbon
      monoxide (CO) poisoning. Hyperbaric oxygen (HBO2) therapy reduces the incidence
      of cognitive and neurological a dysfunction. The efficacy of providing HBO2
      beyond the first one to two days after initial insult is unknown. However, some
      evidence exists for the benefit of this treatment. We report on treating a
      patient 14 months after CO injury, who responded with markedly improved
      neurologic status. A 27-year-old scholar was found comatose due to CO poisoning
      (carboxyhemoglobin = 31.7%). He received five acute HBO2 treatments. After
      discharge, he developed chorea, Parkinsonism, dystonia, memory loss, slowed
      processing speed and verbal fluency, leaving him disabled. After the patient
      reached a clinical plateau, HBO2 was tried again at 90 minutes at 2.4 ATA plus
      air breaks. Neuropsychological testing was performed at baseline and after each
      20 HBO2 cycles, five of which were performed during the period from 14-22 months
      after CO exposure. After the first 20 treatments, Parkinsonism and dystonia
      improved. After 40 sessions, further improvements were seen on mental speed,
      verbal fluency, and fine motor movements. The outcome following 100 treatments
      was that the patient regained independence, including the ability to drive and to
      become gainfully employed. Our case calls into question the concept that HBO2
      therapy has no role during the chronic phase of CO brain injury. Randomized
      clinical trials should be considered to evaluate the therapeutic efficacy of HBO2
      in patients with neurological sequelae following CO injury.

PMID- 29571237
TI  - An approach to treating a patient with a HeartMate IITM left ventricularassist
      device in a multiplace hyperbaric chamber: a case report.
AB  - Introduction: Left-ventricular assist devices (LVAD) are becoming a common
      therapy for end-stage heart failure. These devicesare not tested for
      pressurization in a hyperbaricchamber by the manufacturer. In this article, we
      present an approach to modify the power supply in order to safely treat a patient
      with an LVAD. Materials and Methods: Our patient had a HeartMateIITM LVAD and
      presented for hyperbaric oxygen treatments for severe radiation cystitis. In
      order to modify this patient's equipment to be compliant with NFPA6 safety
      standards we made several modifications. In brief, this included eliminating the
      usage of lithium-ion batteries, modifying the cord to be compatible with Fink
      chamber outlets, and enclosing the power module in a nitrogen purge. We then used
      a mock circulatory system to test our modifications and make sure the LVAD
      continued to have appropriate flow rates. We then conducted training for staff
      and developed a disaster plan should the LVAD fail at any point. Results: Once we
      felt comfortable with the modifications and had a plan developed should any
      problems arise, we then proceeded to treat our patient in the hyperbaric chamber.
      He successfully underwent 44 hyperbaric treatments for radiation cystitis without
      complications. Conclusion: This case is the second reported patient in the
      literature with an LVAD that was successfully treated in a multiplace hyperbaric
      chamber. As LVADs become increasingly popular to manage heart failure, more
      patients with these devices will present for hyperbaric treatments. With a few
      modifications, an LVAD patient can be safely and successfully treated in a
      hyperbaric chamber.

PMID- 29571238
TI  - Hemiplegia and bilateral globus pallidus infarcts after carbon monoxide
      poisoning: case report.
AB  - The vast clinical manifestations of carbon monoxide (CO) poisoning can involve
      the neurological, neuropsychological and cardiac systems as well as others. In
      this case report, we describe our management of a 64-year-old woman exposed to CO
      in her apartment. Her presentation was unusual in that she had symmetric globus
      pallidus lesions, no evidence of thrombosis, but the lateralizing neurologic
      manifestation of severe hemiplegia.

PMID- 29571239
TI  - Management of central retinal artery occlusion following successful hyperbaric
      oxygen therapy: case report.
AB  - Objective: This case report presents a patient with central retinal artery
      occlusion (CRAO) who was successfully treated with hyperbaric oxygen (HBO2) but
      subsequently suffered a recurrence of his visual loss. Methods: CRAO may be
      treated successfully with HBO2 if treatment is undertaken promptly after the
      onset of vision loss. The goal of HBO2 therapy is to oxygenate the ischemic inner
      retinal layers via diffusion from the hyperoxygenated choroidal circulation until
      recanalization of the central retinal artery occurs. Results: A 71-year-old man
      presented with hand motion vision and fundus findings of CRAO in his left eye.
      Treatment with HBO2 was initiated approximately 9.5 hours after loss of vision.
      The patient experienced return of vision to a near-normal level during HBO2. His
      vision loss recurred, however, 15 minutes after the HBO2 session. There was a
      delay to follow-up HBO2 treatments, and the improvement of vision that resulted
      from these subsequent HBO2 sessions was much less than that experienced during
      his initial HBO2 treatment. Conclusion: Recovery of vision during initial HBO2
      treatment indicated that this patient's retina had not yet suffered irreversible
      ischemic damage at that point in time. CRAO patients with a good result from
      initial HBO2 treatment should be admitted to a stroke center and should have
      their visual status monitored hourly. Should vision loss recur, aggressive use of
      intermittent 100% normobaric and hyperbaric oxygen is indicated to preserve
      retinal function until central retinal artery recanalization occurs. An evidence
      based management plan for such patients is presented.

PMID- 29571240
TI  - Re: Evaluation of regulator performance in polar diving.

PMID- 29571241
TI  - Re: Evaluation of regulator performance in polar diving - authors' response.

PMID- 29571242
TI  - Hyperbaric oxygen therapy in the treatment of ischemic lower extremity ulcers in
      patients with diabetes: Results of the DAMO2CLES multicenter randomized clinical
      trial. Commentary on article in Diabetes Care.

PMID- 29571243
TI  - Curcumin ameliorated ventilator-induced lung injury in rats.
AB  - BACKGROUND: Curcumin (CUR) is a Chinese medicine monomer with antioxidant and
      anti-inflammatory properties. The aim of this study was to investigate the
      effects and mechanisms of CUR treatment on ventilator-induced lung injury (VILI)
      in rats. METHODS: Total 50 SD rats were divided into five groups: sham, VILI,
      VILI+CUR-50 (CUR 50?mg/kg pretreated intraperitoneal), VILI+CUR-200 (CUR
      200?mg/kg pretreated intraperitoneal) and VILI?+?DXM (5?mg/kg pretreated
      intraperitoneal). The morphology and ultrastructure were observed by microscope
      and transmission electron microscope. The wet to dry ratio, protein concentration
      in bronchoalveolar lavage fluid (BALF), evans blue dye (EBD) content, nuclear
      factor kappa B (NF-?B) activity, myeloperoxidase (MPO), malondialdehyde (MDA),
      xanthine oxidase (XO) and total antioxidative capacity (TAOC) levels were
      measured. RESULTS: Histological studies revealed that inflammatory cells
      infiltration and alveolar edema were significantly severe in VILI as compared to
      other groups. CUR-200 and DXM treatment reversed lung injury significantly. The
      wet to dry ratio, protein concentration in BALF, EBD content, MPO activity, tumor
      necrosis factor (TNF)-? level and NF-?B activity were significantly increased in
      VILI group as compared to other groups. CUR-200 and DXM treatment significantly
      suppressed permeability and inflammation induced by ventilation. Furthermore, the
      significantly higher MDA content in VILI could be markedly decreased by CUR-200
      and DXM treatment while the levels of XO and TAOC were markedly recovered only by
      CUR (200?mg/kg) treatment after VILI. CONCLUSION: CUR could inhibit the
      inflammatory response and oxidative stress during VILI, which is partly through
      NF-?B pathway.

PMID- 29571244
TI  - 1,3,7-Trihydroxyxanthone, derived from Polygalae Radix, a herbal medicine,
      stimulates the expression of neurotrophic factors in rat astrocyte primary
      cultures via cAMP- and ERK-dependent pathways.
AB  - 1,3,7-Trihydroxyxanthone is a compound isolated from Polygalae Radix, a medicinal
      herb frequently applied for treatment of psychiatric disordres with symptoms of
      forgetfulness and depression in ancient China. In current research, this compound
      was applied onto rat astrocyte primary cultures in exploring the action
      mechanisms of 1,3,7-trihydroxyxanthone on regulating synthesis of neurotrophic
      factors. It was found that 1,3,7-trihydroxyxanthone could significantly stimulate
      the expression of NGF and BDNF in dose-dependent manners: the stimulation was
      both in mRNA and protein levels. Furthermore, 1,3,7-trihydroxyxanthone might
      fulfill this effect by regulating critical enzymes, such as plasminogen, tissue
      plasminogen activator, neuroserpin and tissue inhibitor of metalloproteinases in
      metabolic pathway of neurotrophic factors. Besides, inhibitors of cAMP- and ERK
      dependent pathways, which implied the possible signaling pathway, could reverse
      this inducing effect. These results might support the potentiality of 1,3,7
      trihydroxyxanthone in drug development in treating psychiatric disorders.

PMID- 29571245
TI  - Rosemary extract modulates fertility potential, DNA fragmentation, injury, KI67
      and P53 alterations induced by etoposide in rat testes.
AB  - Etoposide is a semi-synthetic compound derived from the plant podophyllum
      pelltatum and are antineoplastic agents long been used for treatment of human
      malignancies. The present study was conducted to examine the possible modifying
      effects of rosemary aqueous extract against sperm abnormalities, testes injury,
      DNA fragmentation, apoptosis and Ki67 alterations induced by Etoposide in male
      rats. A total of 50 adult male rats were divided into 5 groups (1st, control;
      2nd, rosemary; 3rd, Etoposide; 4th, co-treated Etoposide with rosemary; 5th, post
      treated Etoposide with rosemary). Sperms counts, motility and viability and KI67
      immunoreactivity in testes were significantly decreased while; sperm
      abnormalities, testicular injury, P53 and DNA damage were a significantly
      increased in Etoposide group as compared to control group. Co-administration of
      rosemary with Etoposide improved the sexual toxicity, fertility potential,
      testicular injury, KI67, P53 and DNA damage induced by Etoposide. Etoposide
      treatment induced depletion in counts, motility and viability of rat sperms.
      Etoposide treatment induced testicular DNA damage, injury and decreased in KI67
      and P53 expressions. Treatment with rosemary with Etoposide improved these
      alterations.

PMID- 29571246
TI  - Hsa_circ_0014717 is downregulated in colorectal cancer and inhibits tumor growth
      by promoting p16 expression.
AB  - Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that may
      regulate gene expression in eukaryotes. Nevertheless, their potential functions
      in human malignancies are still largely unknown. The aim of this study was to
      explore the expression of hsa_circ_0014717 in colorectal cancer (CRC) and its
      role involving in tumor growth. We found that hsa_circ_0014717 was downregulated
      in CRC tissues and cell lines, and was significantly correlated with TNM stage,
      distal metastasis and poor overall survival of CRC patients as well. Moreover,
      our gain-of-function analysis further showed that hsa_circ_0014717 overexpression
      could significantly suppress CRC cell proliferation and colony formation, as well
      as induce cell cycle G0/G1 phase arrest in vitro and inhibit xenograft tumor
      growth in vivo. In addition, hsa_circ_0014717 could upregulate the expression of
      cell cycle inhibitory protein p16. Besides, p16 knockdown could reverse
      hsa_circ_0014717 mediated growth inhibition of CRC cells. Taken together,
      hsa_circ_0014717 acts as a potential tumor suppressor that inhibits CRC growth,
      partly at least, through upregulating p16 expression. Furthermore, our present
      study may provide a promising therapeutic target for CRC patients.

PMID- 29571247
TI  - Comprehensive analysis and experimental verification of LINC01314 as a tumor
      suppressor in hepatoblastoma.
AB  - Hepatoblastoma (HB), as a common pediatric liver malignancy, is composed of a
      variety of subgroups with different clinical outcomes. Long-noncoding RNA
      (lncRNA) has crucial roles in cancer biology. However, the association between
      lncRNA and HB has not been fully investigated. In this study, we screened lncRNA
      expression profiles that were annotated from the GSE75271 dataset. A total of 225
      differentially expressed lncRNAs (DELs) were identified based on comparison
      between three prognostic subgroups, and seven of them (XR_241302, XR_923061,
      NR_038322, XR_951687, XR_934593, NR_120317 and XR_93406) that exhibited highly
      predictive accuracies were selected for functional analysis. Weighted gene
      correlation network analysis (WGCNA) was employed to predict the biological
      functions of the seven DELs. The Hippo-YAP signaling pathway was predicted to be
      the most statistically significant predicted pathway associated with the seven
      DELs. Furthermore, we performed in vitro experiments to validate the biological
      function of one DEL, NR_120317 (LINC01314). Our results showed decreased
      proliferation and migration activities of HB cells overexpressing LINC01314.
      Moreover, mechanistic investigations revealed that LINC01314 overexpression
      inhibited nuclear translocation of YAP, by inducing MST1 expression and promoting
      phosphorylation of LATS1 and YAP, consequently downregulating the expression of
      cell cycle regulatory proteins (MCM7 and cyclin D1). Taken together, our findings
      provide evidence for LINC01314 as a potential biomarker and anti-cancer
      therapeutic target in patients with HB.

PMID- 29571248
TI  - Anti-inflammatory and anti-tumor effects of alpha-l-guluronic acid (G2013) on
      cancer-related inflammation in a murine breast cancer model.
AB  - Cancer-related inflammation (CRI) is associated with the malignant progression of
      several cancer types. Targeting these pathways is a novel promising strategy for
      cancer prevention and treatment. In this present study, we evaluated the efficacy
      of ?-l-guluronic acid (ALG), a potent anti-inflammatory agent on breast cancer
      related inflammation both in vitro and in vivo conditions. Our results indicated
      that ALG can effectively inhibit the CRI and tumor-promoting mediators (COX-2,
      MMP2, MMP9, VEGF and proinflammatory cytokines) without direct toxic effects on
      the cells. Moreover, it was found that, ALG can effectively inhibit the tumor
      cell adhesion to extracellular matrix, seeding in implantation tissue, reduce
      accumulation of immunosuppressive and inflammatory cells in tumor-bearing mice.
      These findings were associated with decreased tumor growth, metastasis,
      angiogenesis and prolonged mice survival. In conclusion, our data provide a
      cellular and molecular justification for the use of nonsteroidal anti
      inflammatory drugs (NSAIDs) in treating cancer and imply the potential anti-tumor
      activity of ALG therapy via inhibition of CRI. These findings could lead to the
      establishment of novel NSAID-based cancer therapy in the near future and open a
      new horizon for cancer treatment.

PMID- 29571249
TI  - Thymoquinone reduces mortality and suppresses early acute inflammatory markers of
      sepsis in a mouse model.
AB  - BACKGROUND: Sepsis is a severe systemic condition caused by an excessive
      inflammatory response to microbial infections, which often results in high
      mortality. AIMS: In the present study, the therapeutic effects of thymoquinone
      were investigated for Gram-negative bacteria-induced sepsis in mice. METHODS:
      Thymoquinone was administered as 1or 2?mg/kg intraperitoneally 2?h after
      Escherichia coli (E. coli) challenge. Animal morality was assessed up to 96?h
      post infection and inflammatory proteins levels were measured 6?h after
      thymoquinone treatment in various groups using enzyme-linked immunosorbent assay
      (ELISA) techniques. KEY FINDINGS: The E. coli inoculation markedly increased the
      level of plasma cytokines, including tumor necrosis factor (TNF)-?, interleukin
      (IL)-1, IL-2, IL-6 and IL-10. In addition, the levels of selected early sepsis
      biomarkers such as CRP, VEGF and ESM-1 were amplified in the septic group.
      Treatment with thymoquinone significantly downregulated the circulating
      concentrations of the inflammatory proteins (p?<?0.05). In addition, ?75% of mice
      in the thymoquinone (1?mg/kg) group survived at 96h of observation compared with
      ?8% of the untreated group (p?=?0.0016). SIGNIFICANCE: The present results
      indicate that thymoquinone suppresses acute inflammatory responses induced by
      sepsis including early stage biomarkers and reduces sepsis-related mortality.
      These findings suggest that thymoquinone could be of a potential therapeutic
      value in the management of sepsis.

PMID- 29571250
TI  - Baicalein sensitizes hepatocellular carcinoma cells to 5-FU and Epirubicin by
      activating apoptosis and ameliorating P-glycoprotein activity.
AB  - Hepatocellular carcinoma (HCC) has a dismal prognosis in part because of multi
      drug resistance (MDR). Baicalein is a flavonoid extracted from Radix Scutellariae
      with anti-HCC activity. We tested the effects of Baicalein on multi-drug
      resistant HCC cells (Bel7402/5-FU) known to be resistant to the anticancer drugs
      5-FU and Epirubicin. Flow cytometry analysis showed that treatment with 5??g/ml
      and 10??g/ml Baicalein resulted in increases in the intra-cellular concentrations
      of Rho123 and Epirubicin in the corresponding group of cells compared to
      untreated cells, illustrating that Baicalein reverses MDR in Bel7402/5-FU cells.
      Bel7402/5-FU cells displayed increased P-glycoprotein (P-gp)-mediated drug
      efflux. However, this efflux was inhibited in cells pre-incubated in Baicalein
      for 48?h. Moreover, Baicalein induced apoptosis and autophagy and decreased P-gp
      and Bcl-xl expression levels. All of these results indicate that Baicalein can
      reverse P-gp-mediated MDR in HCC and may thus be useful for the treatment of drug
      resistant HCC.

PMID- 29571251
TI  - Hyaluronic acid modified nanostructured lipid carriers for transdermal
      bupivacaine delivery: In vitro and in vivo anesthesia evaluation.
AB  - For effective transdermal local anesthetic therapy, to reduce the barrier of
      stratum corneum and improve the antinociceptive effect, hyaluronic acid (HA)
      modified, bupivacaine (BPV) loaded nanostructured lipid carriers (NLCs) were
      designed. HA and linoleic acid (LOA) conjugated propylene glycol (PEG) was
      synthesized (HA-PEG-LOA). HA-PEG-LOA was added during the preparation process of
      NLCs, thus LOA was inserted into the NLCs, The physicochemical properties of
      NLCs, particle size, zeta potential, drug loading capacity, in vitro skin
      permeation, drug release profiles and in vivo therapeutic effect were evaluated.
      HA-BPV/NLCs have small particle size of 150?nm, with a zeta potential of ?40?mV.
      Nearly 90% high drug encapsulation efficiency and good stability were also
      observed. In vitro release rate of BPV from HA-BPV/NLCs was complying with a
      sustained behavior until 72?h of study. HA-BPV/NLCs and BPV/NLCs exhibited 2.5
      and 1.6 fold of percutaneous penetration improvement than free BPV. BPV loaded
      NLCs produced a more prolonged antinociceptive effect when compared with free
      BPV. In vitro and in vivo results pointed out HA modified NLCs have the
      capability to act as effective drug carriers, thus prolonging and enhancing the
      anesthetic effect of BPV. The NLCs developed in this study might provide a useful
      platform for developing a sophisticated dermal delivery system for analgesic.

PMID- 29571252
TI  - Hepatoprotective effects of capsaicin and alpha-tocopherol on mitochondrial
      function in mice fed a high-fat diet.
AB  - Capsaicin (CAP) and alpha-tocopherol (TOC) have antioxidant properties. We
      investigated effects of CAP and TOC on mitochondrial oxidative stress and
      mitochondrial bioenergetics in liver of mice fed HFD. AST, ALT, glucose,
      homeostasis model assessment-insulin resistance index ((HOMA-IR)) and
      mitochondrial oxidative stress parameters increased, whereas oxidative
      phosphorylation (OXPHOS) enzymes, tricarboxylic acid cycle (TCA) enzymes, ATP
      level and mitochondrial metabolic function (MTT) decreased in mice fed a HFD
      compared to the fed a standard diet (NC). Treatment of HFD together with CAP (HFC
      group), TOC (HFT group) or TOC and CAP (HCT group) can ameliorate the examined
      parameters. Because co-treatment with CAP and TOC displayed a better ameliorating
      effect on liver redox status and mitochondrial bioenergetics functions, they can
      be useful to protect against HFD and oxidative stress-related in liver diseases.

PMID- 29571253
TI  - In vitro inhibited effect of gap junction composed of Cx43 in the invasion and
      metastasis of testicular cancer resistanced to cisplatin.
AB  - The effect of gap junction intercellular communication composed of connexin on
      cancer invasion/metastasis has been thoroughly explored; however, its effect on
      testicular cancer resistanced to chemotherapy is still unclear. In this study, we
      found that the capability of invasion and migration of I-10/DDP (cisplatin (DDP)
      resistance) cells were elevated. Furthermore, the expression of Cx43 and the
      function of gap junction (GJ) in I-10/DDP cells were decreased compared with
      parental I-10 cells. Pharmacological inhibition of GJs by oleamide (Olea)
      enhanced invasion and migration. However, enhancement of GJs by retinoic acid
      (RA) decreased invasion and migration of I-10/DDP cells. To further clarify the
      invasion/migration inhibited effect of GJ in the testicular cancer resistanced to
      DDP, GJ function was modulated by overexpression and knockdown of Cx43
      expression. Overexpression of Cx43 reduced invasion and migration of I-10/DDP
      cells. Conversely, knockdown of Cx43 expression increased invasion and migration
      of I-10/DDP cells. In summary, GJ composed of Cx43 inhibits I-10/DDP cells
      invasion and migration, and it may become the potential therapeutic target for
      testicular cancer chemotherapy.

PMID- 29571254
TI  - Er Shen Wan extract reduces diarrhea and regulates AQP 4 and NHE 3 in a rat model
      of spleen-kidney Yang deficiency-induced diarrhea.
AB  - INTRODUCTION: Er Shen Wan (ESW), a traditional Chinese medicinal formula
      comprised of Psoraleae Fructus (Babchi seeds, from Psoralea corylifolia Linn.)
      and Myristicae Semen (Nutmeg, from Myristica fragrans Houtt.), is widely used to
      treat spleen-kidney Yang deficiency (SKYD)-induced diarrhea. Previous studies
      have demonstrated preliminarily that the petroleum ether extract of ESW (ESWP)
      exhibits significant anti-diarrheal activity. The present study aimed to evaluate
      the anti-diarrhea activity of ESWP and to explore the underlying mechanisms with
      respect to fluid metabolism in a rat model of SKYD-induced diarrhea. MATERIALS
      AND METHODS: A high-performance liquid chromatography-diode array detector (HPLC
      DAD) approach was developed and validated for qualitative and quantitative
      analyses of the main constituents of ESWP. SKYD model rats were established and
      treated with an effective dose (3.5?g/kg) of the extract for two weeks. Anti
      diarrheal activity and stool properties were observed. After the experiment, the
      appearance and histology of the intestines were evaluated. Serum levels of
      neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were also
      determined. Furthermore, to characterize the regulation of aquaporin-4 (AQP 4)
      and Na+/H+ exchanger isoform 3 (NHE 3) in the colon, quantitative real-time RT
      PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) were employed
      to detect mRNA and protein expression levels. RESULTS: In the rat models, oral
      ESWP administration significantly reduced the diarrhea score and the number and
      weight of wet stools. Jejunal and ileac histological damage was impeded, and the
      histology score decreased. Serum VIP levels were significantly decreased, in
      contrast to NPY levels. In addition, AQP 4 and NHE 3 expression levels increased
      significantly. CONCLUSIONS: These results showed that ESWP's anti-diarrheal
      effect might at least partially involve the regulation of hormones intimately
      involved in maintaining fluid and electrolyte levels, as well as by increasing
      AQP 4 and NHE 3 expression levels and enhancing the absorption of Na+ and water.

PMID- 29571256
TI  - Hydrogen sulfide upregulated lncRNA CasC7 to reduce neuronal cell apoptosis in
      spinal cord ischemia-reperfusion injury rat.
AB  - OBJECTIVE: Hydrogen sulfide has been recognized as an important neuroprotective
      agent in the nervous system. The present study aimed to study the effect and the
      underlying mechanisms of hydrogen sulfide on spinal cord ischemia-reperfusion
      injury (SCII). METHODS: The gene mRNA and protein expression were examined by RT
      PCR and western blot, respectively. Spinal cord infarct zone was analyzed by
      Triphenyltetrazolium chloride staining. Cell apoptosis was detected by MTT assay.
      The relationship between miR-30c and CasC7 was analyzed by RNA
      immunoprecipitation (RIP) and RNA pull-down. RESULTS: We observed that SCII rat
      model have a bigger spinal cord infarct zone than the control rat, but NaSH
      preprocessing could reduce spinal cord infarct zone in SCII rat. OGD/R induced
      cell apoptosis, and NaSH preprocessing reduced the OGD/R-induced SH5Y-SY cells
      apoptosis. CasC7 was decreased in SCII rat and OGD/R-induced SH5Y-SY cells, while
      miR-30c expression was increased. NaSH preprocessing upregulated CasC7 and
      downregulated miR-30c in OGD/R-induced SH5Y-SY cells. In OGD/R induced SH5Y-SY
      cells with NaSH preprocessing, knockdown of CasC7 could upregulate miR-30c
      expression, promote cell apoptosis and downregulate miR-30c's target gene
      expression. The RIP and RNA pull-down demonstrated that CasC7 functioned as a miR
      30c decoy, and miR-30c inhibitor could reverse the effect of si-CasC7. Moreover,
      intrathecal injection of si-CasC7 upregulated miR-30c expression and increased
      spinal cord infarct zone in SCII rat with NaSH preprocessing. CONCLUSION:
      Hydrogen sulfide protects spinal cord by upregulating CasC7 expression in SCII
      rat model.

PMID- 29571255
TI  - Inhibition of PDGF-BB-induced proliferation and migration in VSMCs by
      proanthocyanidin A2: Involvement of KDR and Jak-2/STAT-3/cPLA2 signaling
      pathways.
AB  - Proanthocyanidin A2 (PA2), one of A-type proanthocyanidins, has been shown to
      harbor a broad spectrum of pharmacological activities, including anti
      inflammatory, antioxidant, anti-HIV, anti-CDV and anti-?-glucosidase activities.
      However, little is known about the role for PA2 in regulating PDGF-induced VSMC
      proliferation and migration. In the present study, we investigated the possible
      effects of PA2 on PDGF-BB-induced proliferation, migration and inflammation in
      VSMCs in vitro to mimic a postangioplasty PDGF shedding condition. Herein, the
      data clearly show that PA2 markedly inhibited proliferation, migration and
      inflammatory responses at 0-30??g/ml concentration in VSMCs in vitro. 10-30??g/ml
      PA2 inhibited PDGF-mediated NAD(P)H oxidase activation and intracellular ROS
      formation in VSMCs. Furthermore, the effects exerted by PA2 involve the
      participation of KDR and Jak-2/STAT-3/cPLA2 signaling pathways. These data also
      highlight the possible therapeutic use of PA2 in vascular proliferative diseases,
      where abnormal proliferation and migration play important pathological roles.

PMID- 29571257
TI  - Tocoyena sellowiana extract decreases bone loss in an experimental model of
      periodontitis in rats: Putative role for cyclooxygenase-2 and IL-1? inhibition.
AB  - Tocoyena sellowiana (Cham. & Schltdl.) K.Schum is one of the most important
      families of Brazilian medicinal plants. This study aimed to evaluate the effect
      of Tocoyena sellowiana (Cham. & Schltdl.) K.Schum ethanolic extract in a pre
      clinical trial of periodontitis and to investigate possible mechanisms underlying
      such effects. Periodontitis was induced in Wistar rats by placing a nylon thread
      ligature around second upper left molars for 11 days. Rats received (per os)
      Tocoyena sellowiana (0.1, 1 or 10?mg?kg) or vehicle 1?h before ligature and daily
      until day 11. Macroscopic, histopathological, and COX-2 immunohistochemical
      analyses were performed to evaluate the periodontium. The gingival tissue was
      used to quantify the myeloperoxidase (MPO) activity and interleukin (IL)-1?
      levels by ELISA. Blood samples were collected to evaluate bone-specific alkaline
      phosphatase (BALP), the dosage of creatinine, aspartate and alanine
      transaminases. The liver, kidneys, spleen, and body mass variations were also
      evaluated. Tocoyena sellowiana decreased bone loss, reduced MPO, IL-1? levels as
      well as COX-2 immunostaining, and increased BALP activity. Moreover, Tocoyena
      sellowiana did not alter organs nor body weight. Tocoyena sellowiana reduced bone
      loss in rats and its efficacy was at least partially dependent upon both IL-1?
      and cyclooxygenase-2 inhibition.

PMID- 29571258
TI  - Analysis of antioxidant, cytotoxic and mutagenic potential of Agave sisalana
      Perrine extracts using Vero cells, human lymphocytes and mice polychromatic
      erythrocytes.
AB  - Brazilian Northeast is the world's largest producer of Agave sisalana Perrine for
      the supply of the sisal fiber. About 95% of plant biomass, which comprise the
      mucilage and sisal juice, is considered a waste residual is discarded in the
      soil. However, the sisal juice is rich in steroidal saponins, which exhibits
      different pharmacological properties. Despite this, natural products are not
      necessarily safe. Based on this, this study analyzed the antioxidant, cytotoxic
      and mutagenic potential of three extracts derived from acid hydrolysis (AHAS),
      dried precipitate (DPAS) and hexanic of A. sisalana (HAS). These analyses were
      performed by in vitro and in vivo methods, using Vero cells, human lymphocytes
      and mice. Results showed that AHAS 50 and 100 can be considered a useful
      antineoplastic candidate due to their antioxidant and cytotoxic activity, with no
      genotoxic/clastogenic potential in Vero cells and mice. Although the comet assay
      in human lymphocytes has showed that the AHAS 25, AHAS 50 and AHAS 100 can lead
      to DNA breaks, these extracts did not promote DNA damages in mice bone marrow.
      Considering the different mutagenic responses obtained with the different methods
      employed, this study suggest that the metabolizing pathways can produce by
      products harmful to health. For this reason, it is mandatory to analyze the
      mutagenic potential by both in vitro and in vivo techniques, using cells derived
      from different species and origins.

PMID- 29571259
TI  - Diversity and functional evolution of the plasminogen activator system.
AB  - The urokinase plasminogen activator system is a family of serine proteases which
      consists of uPA (urokinase plasminogen activator), uPAR (urokinase type
      plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1). In
      addition to their significant roles in activation, these proteases act as key
      regulators of the tumor microenvironment and are involved in the metastatic
      process in many cancers. High levels of uPA system proteases in many human cancer
      predicts poor patient prognosis and strongly indicated a key role of uPA system
      in cancer metastasis. Individual components of uPA system are found to be
      differentially expressed in cancer cells compared to normal cells and therefore
      are potential therapeutic targets. In this review, we present the molecular and
      cellular mechanisms underlying the role of uPA system in cancer progression.
      Epithelial to mesenchymal transitions (EMT) is the main cause of the cancer cell
      metastasis. We have also attempted to relate the role of uPA signaling in EMT of
      cancer cells.

PMID- 29571260
TI  - Knockdown of long non-coding RNA HOXD-AS1 inhibits the progression of
      osteosarcoma.
AB  - Long non-coding RNA HOXD-AS1 (HOXD-AS1) has recently been shown to be involved in
      the development and progression of multiple cancers. However, the expression,
      significance, and biological function of HOXD-AS1 in osteosarcoma (OS) remain
      unknown. Here, we found that the expression level of HOXD-AS1 was significantly
      upregulated in OS tissues and cells. Furthermore, high expression of HOXD-AS1 was
      positively associated with the clinical and pathological characteristics of OS,
      including tumor stage and lymph node metastasis, and negatively correlated with
      overall survival rate. in vitro assays confirmed that knockdown of HOXD-AS1
      suppressed cell proliferation, colony formation, migration, and invasion, and
      promoted cell cycle arrest at G1 stage and apoptosis in OS cells. in vivo assays
      confirmed that knockdown of HOXD-AS1 significantly decreased tumor growth in
      xenograft mice, and decreased tumor size and weight. Importantly, we also showed
      that knockdown of HOXD-AS1 significantly reduced signal transducer and activator
      of transcription 3 and its target protein (CyclinD1, Bcl-2, and MMP-2) expression
      in vitro and in vivo. Moreover, overexpression of STAT3 could reverse the
      suppression of proliferation ability induced by sh-HOXD-AS1 in U2OS cells.
      Collectively, our data indicated that HOXD-AS1 might be an oncogenic long non
      coding RNA (lncRNA) and might be a potential attractive therapeutic target for
      OS.

PMID- 29571261
TI  - Genomic stability and telomere regulation in skeletal muscle tissue.
AB  - Muscle injuries are common, especially in sports and cumulative trauma disorder,
      and their repair is influenced by free radical formation, which causes damages in
      lipids, proteins and DNA. Oxidative DNA damages are repaired by base excision
      repair and nucleotide excision repair, ensuring telomeric and genomic stability.
      There are few studies on this topic in skeletal muscle cells. This review focuses
      on base excision repair and nucleotide excision repair, telomere regulation and
      how telomeric stabilization influences healthy muscle, injured muscle, exercise,
      and its relationship with aging. In skeletal muscle, genomic stabilization and
      telomere regulation seem to play an important role in tissue health, influencing
      muscle injury repair. Thus, therapies targeting mechanisms of DNA repair and
      telomeric regulation could be new approaches for improving repair and prevention
      of skeletal muscle injuries in young and old people.

PMID- 29571262
TI  - Efficient Charge Separation in Plasmonic ZnS@Sn:ZnO Nanoheterostructure:
      Nanoscale Kirkendall Effect and Enhanced Photophysical Properties.
AB  - Tetravalent Sn doped ZnO nanocrystals show excellent plasmonic absorbance in the
      visible region. Plasmonic ZnS@Sn:ZnO core-shell heterostructures have been
      synthesized by the anion exchange process where the O2- is exchanged by S2-
      anion. An increase of sulfur concentration induces interior hollow structures
      arising from the different diffusion rates of O2- and S2- ions. Gradual
      transformation of wurtztie ZnO nanocrystals in the anion exchange process
      stabilizes the wurtzite crystalline phase of ZnS. Carrier concentration and
      various types of intrinsic defect states in both ZnO and ZnS result in
      ultraviolet, blue, and green emissions. The coexistence of exciton-plasmon
      coupling in the same nanoparticle and efficient electron-hole separation in type
      II heterostructure increases the photocatalytic activity and photo current gain.

PMID- 29571263
TI  - Comparative study on antibody immobilization strategies for efficient circulating
      tumor cell capture.
AB  - Methods for isolation and quantification of circulating tumor cells (CTCs) are
      attracting more attention every day, as the data for their unprecedented clinical
      utility continue to grow. However, the challenge is that CTCs are extremely rare
      (as low as 1 in a billion of blood cells) and a highly sensitive and specific
      technology is required to isolate CTCs from blood cells. Methods utilizing
      microfluidic systems for immunoaffinity-based CTC capture are preferred,
      especially when purity is the prime requirement. However, antibody immobilization
      strategy significantly affects the efficiency of such systems. In this study, two
      covalent and two bioaffinity antibody immobilization methods were assessed with
      respect to their CTC capture efficiency and selectivity, using an anti-epithelial
      cell adhesion molecule (EpCAM) as the capture antibody. Surface functionalization
      was realized on plain SiO2 surfaces, as well as in microfluidic channels.
      Surfaces functionalized with different antibody immobilization methods are
      physically and chemically characterized at each step of functionalization. MCF-7
      breast cancer and CCRF-CEM acute lymphoblastic leukemia cell lines were used as
      EpCAM positive and negative cell models, respectively, to assess CTC capture
      efficiency and selectivity. Comparisons reveal that bioaffinity based antibody
      immobilization involving streptavidin attachment with glutaraldehyde linker gave
      the highest cell capture efficiency. On the other hand, a covalent antibody
      immobilization method involving direct antibody binding by N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)-N
      hydroxysuccinimide (NHS) reaction was found to be more time and cost efficient
      with a similar cell capture efficiency. All methods provided very high
      selectivity for CTCs with EpCAM expression. It was also demonstrated that
      antibody immobilization via EDC-NHS reaction in a microfluidic channel leads to
      high capture efficiency and selectivity.

PMID- 29571264
TI  - White Matter Connectivity of the Visual-Vestibular Cortex Examined by Diffusion
      Weighted Imaging.
AB  - The parieto-insular vestibular cortex (PIVC) and the posterior insular cortex
      (PIC) are key regions of the cortical vestibular network, both located in the
      midposterior section of the lateral sulcus. Little is known about the structural
      connectivity pattern of these areas. We used probabilistic fiber tracking based
      on diffusion-weighted magnetic resonance imaging (MRI) and compared the
      ipsilateral connectivity of PIVC and PIC. Seed areas for the tracking algorithm
      were identified in each brain by functional MRI activity during caloric and
      visual motion stimulation, respectively. Cortical track terminations were
      investigated by a surface-based approach. Both PIVC and PIC shared ipsilateral
      connections to the insular/lateral sulcus, superior temporal cortex, and inferior
      frontal gyrus. However, PIVC showed significantly more connections than PIC with
      the anterior insula and Heschl's gyrus in both hemispheres and with the
      precuneus, intraparietal sulcus, and posterior callosum of the right hemisphere.
      In contrast, PIC connectivity was more pronounced with the supramarginal gyrus
      and superior temporal sulcus. Subcortical tracks were examined by a region-of
      interest-based approach, which was validated on cortico-thalamic motor tracts.
      Both PIVC and PIC were connected with lateral nuclei of the thalamus and the
      basal ganglia (primarily putamen). PIVC tracks but not PIC tracks showed a right
      hemispheric lateralization in cortical and subcortical connectivity. Overall,
      these results suggest that human PIVC and PIC share cortical and even subcortical
      connections. Nevertheless, they also differ in their primary connectivity
      pattern: PIVC is linked with posterior parietal and inferior frontal cortex,
      whereas PIC is linked with superior temporal and inferior parietal cortex.

PMID- 29571265
TI  - Variability of online available physical therapy protocols from academic
      orthopedic surgery programs for arthroscopic meniscus repair.
AB  - OBJECTIVES: To evaluate the variability of arthroscopic meniscus repair
      rehabilitation protocols. METHODS: Arthroscopic meniscus repair rehabilitation
      protocols from Accreditation Council for Graduate Medical Education (ACGME)
      accredited orthopedic surgery programs available online were included for review.
      Data collection was performed to evaluate recommended weight bearing status and
      immobilization as well as the presence or absence of recommended therapies, goals
      for progression of range of motion, functional milestones, and activity
      initiation time points within each protocol. RESULTS: Out of 162 institutions
      available for review, 24 (14.8%) institutions made their protocol available on
      their website, with 28 total protocols available. Initially following repair, 14
      (50%) of the protocols allow for weight bearing as tolerated (WBAT). Of the 14
      protocols, which do not allow immediate weightbearing, average time to WBAT was
      4.7 +/- 1.8 weeks. On average, immobilization was recommended for 6.5 +/- 2.1
      weeks (range 4-12 weeks). A large majority of protocols gave recommendations for
      flexion to 90 degrees (24 protocols, range 1-8 weeks), as well as full range of
      motion (22 protocols, range 6-16 weeks). Active range of motion was recommended
      to begin at 0-6 weeks (average 3.8 +/- 1.9 weeks). Lastly, only 14 protocols
      (50%) gave an actual return to sport, with an average return recommended at 21.9
      +/- 3.4 weeks (range 12-24). CONCLUSION: A minority of ACGME-accredited
      orthopedic surgery programs make their meniscus repair rehabilitation protocols
      available online. Furthermore, protocols were found to be highly variable. This
      discrepancy may lead to confusion among therapists and patients.

PMID- 29571266
TI  - Retrieval activates related words more than presentation.
AB  - Retrieving information enhances learning more than restudying. One explanation of
      this effect is based on the role of mediators (e.g., sand-castle can be mediated
      by beach). Retrieval is hypothesised to activate mediators more than restudying,
      but existing tests of this hypothesis have had mixed results [Carpenter, S. K.
      (2011). Semantic information activated during retrieval contributes to later
      retention: Support for the mediator effectiveness hypothesis of the testing
      effect. Journal of Experimental Psychology: Learning, Memory, and Cognition,
      37(6), 1547-1552. doi: 10.1037/a0024140 ; Lehman, M., & Karpicke, J. D. (2016).
      Elaborative retrieval: Do semantic mediators improve memory? Journal of
      Experimental Psychology: Learning, Memory, and Cognition, 42(10), 1573-1591. doi:
      10.1037/xlm0000267 ]. The present experiments explored an explanation of the
      conflicting results, testing whether mediator activation during a retrieval
      attempt depends on the accessibility of the target information. A target was
      considered less versus more accessible when fewer versus more cues were given
      during retrieval practice (Experiments 1 and 2), when the target had been studied
      once versus three times initially (Experiment 3), or when the target could not be
      recalled versus could be recalled during retrieval practice (Experiments 1-3). A
      mini meta-analysis of all three experiments revealed a small effect such that
      retrieval activated mediators more than presentation, but mediator activation was
      not reliably related to target accessibility. Thus, retrieval may enhance
      learning by activating mediators, in part, but these results suggest the role of
      other processes, too.

PMID- 29571267
TI  - Editorial Comment on: Outpatient Percutaneous Nephrolithotomy: The UC San Diego
      Health Experience by Bechis et al.

PMID- 29571268
TI  - Correction to: Janiec et al. Graft failure and recurrence of symptoms after
      coronary artery bypass grafting.

PMID- 29571269
TI  - A functional assay to identify amyloidogenic light chains.
AB  - INTRODUCTION: Multiple myeloma (MM) and light chain monoclonal gammopathy of
      undetermined significance (LCMGUS) are plasma cell disorders associated with the
      secretion of monoclonal free light-chain (LC) proteins. Due to the high
      concentrations of LC in circulation, both of these populations are at risk for
      developing LC-associated amyloidosis (AL) - a protein misfolding disease
      characterized by the deposition of LC protein fibrils in organs and tissues,
      leading to dysfunction and significant morbidity. At present, accurate
      identification of subjects at risk for developing amyloidosis is not possible,
      but with the advent of novel, amyloid-targeted therapies, identification of pre
      symptomatic individuals is of clinical import. METHODS: To address this, a
      competition assay has been developed to discern LC proteins with enhanced
      amyloidogenic potential. Numerous factors that may influence the efficacy of the
      assay have been evaluated to yield optimal conditions. RESULTS: Using a panel of
      nine patient-derived LC, we have demonstrated that amyloid-associated LC
      inhibited the recruitment of a biotinyl-lambda6 variable domain by homologous
      amyloid-like fibrils significantly more than MM LC (p < .01). CONCLUSION: The
      assay accurately discriminated AL from MM patient populations, suggesting that it
      may aid in the identification of patients with monoclonal gammopathies who have
      an increased risk of developing amyloidosis.

PMID- 29571270
TI  - Human papillomavirus and risk of prostate cancer: a systematic review and meta
      analysis.
AB  - BACKGROUND: There is growing evidence showing a putative association between high
      risk human papillomavirus (HR-HPV) infection and an increased risk of PCa.
      OBJECTIVE: The aim of the current meta-analysis was to evaluate the association
      between HPV infection and PCa risk. METHODS: This analysis was conducted
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      analysis guidelines. We included all studies on HPV DNA or antibodies detected in
      biopsy tissues or sera. Available data were extracted from the article, including
      means and standard deviations in all case-control groups. RESULTS: Thirty studies
      that investigated the link between HPV-16 and -18 were identified as eligible for
      this systematic review and meta-analysis, including a total of 6321 participants.
      The pooled OR showed increased risk of PCa (OR =1.37; p < .01) in men positive
      for HPV-16. There were seven studies with 2391 PCa cases and 4059 controls
      investigating the association between HPV-18 infection and PCa risk. Significant
      heterogeneity between study was found in the pooled analyzes. The pooled OR did
      not show increased risk of PCa (OR =0.80; p = .49) in men positive for HPV-18.
      CONCLUSIONS: This meta-analysis suggests that HPV-16 infection could represent a
      risk factor for PCa, whereas we found no such association for HPV-18. Further
      well-conducted studies could be useful to confirm this conclusion.

PMID- 29571271
TI  - Subgroup effects of occupational therapy-based intervention for people with
      advanced cancer.
AB  - BACKGROUND: Many people with advanced cancer have decreased ability to perform
      activities of daily living (ADL). We recently performed a randomized, controlled
      trial (RCT) assessing the efficacy of an occupational therapy-based program, the
      'Cancer Home-Life Intervention' in people with advanced cancer (N = 242) and
      found no overall effects on ADL ability. However, heterogeneity of treatment
      effect may disguise subgroup differences. OBJECTIVE: To investigate whether
      subgroups of people with advanced cancer gain positive effects from the 'Cancer
      Home-Life Intervention' on ADL ability. MATERIAL AND METHOD: An exploratory
      subgroup analysis including 191 participants from a RCT. The outcome was ADL
      motor ability measured by the Assessment of Motor and Process Skills (AMPS).
      Subgroups were defined by age, gender, years of education, type of primary tumor,
      functional level, and activity problems. RESULTS: The 'Cancer Home-Life
      Intervention' had no statistically significant effect in the six subgroups.
      Modifying effects of age (0.30 [95% CI: -0.05 to 0.64]) and gender (0.23 [95% CI:
      -0.11 to 0.57]) were not found. CONCLUSION: There were no subgroup effects of the
      'Cancer Home-Life Intervention'on ADL motor ability. Some indications suggest
      greater effects for those aged below 69 years; however, this result should be
      interpreted with caution.

PMID- 29571272
TI  - Assessment of frailty syndrome using Edmonton frailty scale in Polish elderly
      sample.
AB  - The aim of the study was to assess the incidence and severity of the frailty
      syndrome assessed with the Edmonton Frailty Scale. This is a cross-sectional
      study conducted among 382 patients (236 men and 146 women, mean age 71.9 years).
      The Edmonton Frailty Scale was administered during the patient's admission to the
      hospital. The Polish adaptation was performed using the standard methodology. The
      Cronbach's alpha coefficient for the whole Edmonton Frailty Scale was 0.709. The
      mean correlation between positions and the overall result was r = 0.180. There
      were no statistically significant differences between women and men in the area
      of Edmonton Frailty Scale mean score (p < 0.05). The socio-clinical analysis,
      showed statistically significant differences in the age of respondents,
      educational attainment, occupational activity, number of drugs taken and co
      occurrence of chronic diseases. A higher values of the Edmonton Frailty Scale
      were indicated for individuals >70 years than for those <70 years (p < 0.001).
      The Edmonton Frailty Scale proved to be a reliable tool which may be used in the
      Polish population. The use of this questionnaire for frailty syndrome may be
      helpful in everyday clinical practice.

PMID- 29571273
TI  - Economic burden of skeletal-related events in patients with multiple myeloma:
      analysis of US commercial claims database.
AB  - AIMS: To estimate incremental healthcare resource utilization (HRU) and costs
      associated with skeletal-related events (SREs) secondary to multiple myeloma
      (MM), and HRU and cost differences in patients with one vs multiple SREs.
      METHODS: Adults with MM diagnosis between January 1, 2010-December 31, 2014, with
      benefits coverage >=12 months pre- and >=6 months post-diagnosis were followed to
      last coverage date or December 31, 2015, excluding patients with prior anti
      myeloma treatment or cancers. SREs were identified by diagnosis or procedure
      codes (pathological fracture, spinal cord compression, radiation, or surgery to
      the bone). SRE patients (index = first post-diagnosis SRE) were propensity score
      matched 1:1 to patients without SRE (assigned pseudo-index) using baseline
      characteristics, and >=1 month of continuous enrollment after index/pseudo-index
      date was required. Per-patient-per year (PPPY) HRU and costs (2016 US$) were
      determined for inpatient, outpatient, emergency department (ED), and outpatient
      pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar's
      tests for proportions were used to assess differences. Negative binomial
      regression and generalized linear regression analyses estimated differences in
      HRU and costs, respectively, for the comparison of single vs multiple SREs.
      RESULTS: Each cohort included 848 patients (mean age = 61 - 62 years, 57% male)
      with no significant differences in pre-index demographic or clinical
      characteristics between matched cohorts. Versus non-SRE patients, SRE patients
      had significantly higher PPPY use (p < .0001) of inpatient hospitalizations, ED
      visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs
      $108,160, p < .0001). Adjusted PPPY total costs were $209,820 in patients with
      multiple SREs; $159,797 in patients with one SRE. LIMITATIONS: SRE
      misclassification and residual confounding are possible. CONCLUSIONS: Among
      patients with MM, average annual costs were substantially higher in patients with
      SRE compared with matched non-SRE patients. The economic burden of SRE increased
      further with multiple events.

PMID- 29571274
TI  - Sound therapy and aural rehabilitation for tinnitus: a person centred therapy
      framework based on an ecological model of tinnitus.
AB  - PURPOSE: Tinnitus is a common oto-neurological complaint often accompanying
      hearing loss. In this perspective on rehabilitation we describe a framework for
      sound therapy and aural rehabilitation of tinnitus based on the ecological model
      of tinnitus. METHOD: A thematic network analysis-based approach was used to
      relate aural rehabilitation methods to the ecological model of tinnitus and the
      client-oriented scale of improvement in tinnitus. RESULTS: Aural rehabilitation
      methods were mapped to concepts of: (1) Context, (2) presence of sound and (3)
      reaction to sound. A global theme was: adaptation to sound. The framework is the
      result of an iterative and cumulative research program exploring tinnitus as the
      outcome of the relationship between individual psychoacoustics and psychosocial
      factors including context of perception. CONCLUSIONS: The intent of this
      framework is to help guide audiologists managing tinnitus. The framework has been
      useful in our clinic as illustrated by a case study. The benefits of this
      approach relative to standard care needs to be independently ascertained.
      Implications for Rehabilitation Tinnitus is a common oto-neurological complaint
      that when severe can be very disabling. Tinnitus is very heterogeneous as a
      consequence of this no one treatment is suitable for everyone. The sound therapy
      and aural rehabilitation for tinnitus framework is designed to assist
      audiologists in clinical planning that addresses individual needs. The framework
      is the result of an iterative and cumulative research program exploring tinnitus
      as the outcome of the relationship between individual psychoacoustics and
      psychosocial factors including context of perception.

PMID- 29571275
TI  - Insulin non-persistence among people with type 2 diabetes: how to get your
      patients to stay on insulin therapy.
AB  - Continuing use of medication is key to effective treatment and positive health
      outcomes, particularly in chronic conditions such as diabetes. However, in
      primary care, non-persistence (i.e. discontinuing or interrupting treatment) with
      insulin therapy is a common problem among patients with type 2 diabetes. To help
      primary care physicians manage patients who are non-persistent or likely not to
      be persistent, this review aimed to provide an overview of modifiable and non
      modifiable factors associated with insulin non-persistence as well as practical
      strategies to address them. Data were extracted from published studies evaluating
      factors associated with non-persistence among patients with type 2 diabetes. A
      targeted literature review was performed using PubMed to identify recent studies
      (2000-2016) reporting measures of non-persistence with insulin therapy. Practical
      strategies to identify and prevent non-persistence were based on the authors'
      direct experience in primary care. Non-modifiable factors associated with non
      persistence included gender, age, prior treatments, and cost of therapy.
      Before/at insulin initiation, modifiable factors included patients' perception of
      diabetes, preference for oral medication, and concerns/expectations about
      treatment complexity, inconvenience, or side effects. After initiation,
      modifiable factors included syringe use, difficulties during the first week of
      therapy, side effects, and insufficient glycemic control. Open-ended and patient
      centered questions and a blame-free environment can help physicians identify,
      prevent, and reduce non-persistence behaviors. Possible questions to start a
      conversation with patients are provided. Effective physician-patient
      communication is essential to the management of diabetes. Primary care physicians
      should be familiar with the most common reasons for insulin non-persistence.

PMID- 29571276
TI  - Estimating the clinical effectiveness and value-based price range of erenumab for
      the prevention of migraine in patients with prior treatment failures: a US
      societal perspective.
AB  - BACKGROUND: Frequent migraine with four or more headache days per month is a
      common, disabling neurovascular disease. From a US societal perspective, this
      analysis models the clinical efficacy and estimates the value-based price (VBP)
      for erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene
      related peptide receptor. METHODS: A Markov health state transition model was
      developed to estimate the incremental costs, quality-adjusted life-years (QALYs),
      and value-based price range for erenumab in migraine prevention. The model
      comprises "on preventive treatment", "off preventive treatment", and "death"
      health states across a 10-year time horizon. The evaluation compared erenumab to
      no preventive treatment in episodic and chronic migraine patients that have
      failed at least one preventive therapy. Therapeutic benefits are based on
      estimated changes in monthly migraine days (MMD) from erenumab pivotal clinical
      trials and a network meta-analysis of migraine studies. Utilities were estimated
      using previously published mapping algorithms. A VBP analysis was performed to
      identify maximum erenumab annual prices at willingness-to-pay (WTP) thresholds of
      $100,000-$200,000 per QALY. Estimates of VBP under different scenarios such as
      choice of different comparators, assumptions around inclusion of placebo effect,
      and exclusion of work productivity losses were also generated. RESULTS: Erenumab
      resulted in incremental QALYs of 0.185 vs supportive care (SC) and estimated cost
      offsets due to reduced MMD of $8,482 over 10 years, with an average duration of
      treatment of 2.01 years. The estimated VBP at WTP thresholds of $100,000-$200,000
      for erenumab compared to SC ranged from $14,238-$23,998. VBP estimates including
      the placebo effect and excluding work productivity ranged from $7,445-$13,809;
      increasing to $12,151-$18,589 with onabotulinumtoxinA as a comparator in chronic
      migraine. CONCLUSION: Erenumab is predicted to reduce migraine-related direct and
      indirect costs, and increase QALYs compared to SC.

PMID- 29571277
TI  - Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration.
AB  - Epidermal cells with stem cell-like characteristics have been identified in the
      tympanic membrane (TM) and localized specifically to the umbo and annulus
      regions. While they have been proposed to play a role in the regeneration of both
      acute and chronic TM perforations, evidence for the mechanism and regulation of
      their contribution is not yet described. Indeed, the behavior of these putative
      stem cells is largely unknown, in part due to a lack of refined methods for
      efficient cell isolation. In this study, we compared different explant techniques
      using normal and perforated rat TM tissues and investigated their ex vivo
      characteristics. TM after perforation in vivo showed increased staining for
      epidermal stem cell markers integrin beta1 and cytokeratin (CK) 19, and for
      proliferation Ki-67, indicating activation of the proliferative centers. A mixed
      population of fibroblasts and epithelial cells were isolated from explant
      cultures. Excised TM umbo implanted on a culture well insert was the most
      effective technique. Explants made from perforated TM produced cells before those
      from unperforated TM. More importantly, the implanted TM umbo organoid was
      capable of producing cells in a continuous manner, allowing subsequent harvest
      using trypsin. Primary rat TM epithelial cell cultures positive for
      pancytokeratin had colony forming activity and could be enriched for CK 19
      positive cells that were capable of culture expansion by proliferation and cell
      migration when subject to a wound assay. Taken together, trauma to the TM
      activated the proliferative centers and prompted early cell production from TM
      umbo organoid cultures, which produced TM stem cell-like cultures that proved
      suitable for tissue engineering of the TM.

PMID- 29571278
TI  - Localizing Global Medicine: Challenges and Opportunities in Cervical Screening in
      an Indigenous Community in Ecuador.
AB  - This participatory research study examines the tensions and opportunities in
      accessing allopathic medicine, or biomedicine, in the context of a cervical
      cancer screening program in a rural indigenous community of Northern Ecuador.
      Focusing on the influence of social networks, the article extends research on "re
      appropriation" of biomedicine. It does so by recognizing two competing tensions
      expressed through social interactions: suspicion of allopathic medicine and the
      desire to maximize one's health. Semistructured individual interviews and focus
      groups were conducted with 28 women who had previously participated in a
      government-sponsored cervical screening program. From inductive thematic
      analysis, the article traces these women's active agency in navigating coherent
      paths of health. Despite drawing on social networks to overcome formidable
      challenges, the participants faced enduring system obstacles-the organizational
      effects of the networks of allopathic medicine. Such obstacles need to be
      understood to reconcile competing knowledge systems and improve health care
      access in underresourced communities.

PMID- 29571279
TI  - Qualitative Assessment of Face Validity and Cross-Cultural Acceptability of the
      Faces Pain Scale: "Revised" in Cameroon.
AB  - The Faces Pain Scale-Revised (FPS-R) is a self-report pain scale validated in
      numerous countries, but not in Cameroon. We postulated that while cultural
      factors influence pain perception and expression, the FPS-R should remain
      culturally acceptable for pediatric use. A convenience sample of 36 pediatric
      patients, aged 4 to 16 years, representing three primary language groups, was
      enrolled at Mbingo Baptist Hospital (MBH). Pre- and postanalgesia FPS-R scores
      and vital signs were obtained. Audio-recorded cognitive interviews were performed
      with each participant. Written questionnaires were also provided to physicians,
      nurses, and caretakers to further explore cultural perceptions of pain. Four
      independent reviewers analyzed interview transcripts and questionnaires using
      inductive reasoning and identified common themes pertaining to gender
      differences, societal roles, and pain perception. Basic comprehension of the FPS
      R was present across language groups, vital sign changes corresponded with FPS-R
      alterations, and the FPS-R appears intuitive for pediatric use.

PMID- 29571280
TI  - GOING LONG AND DIRECT.
AB  - Sarah Webb explores how RNA sequencing innovations help scientists tackle the
      complexity of the transcriptome.

PMID- 29571281
TI  - Use of FTA(r) classic cards for epigenetic analysis of sperm DNA.
AB  - FTA(r) technologies provide the most reliable method for DNA extraction. Although
      FTA technologies have been widely used for genetic analysis, there is no
      literature on their use for epigenetic analysis yet. We present for the first
      time, a simple method for quantitative methylation assessment based on sperm
      cells stored on Whatman FTA classic cards. Specifically, elution of seminal DNA
      from FTA classic cards was successfully tested with an elution buffer and an
      incubation step in a thermocycler. The eluted DNA was bisulfite converted,
      amplified by PCR, and a region of interest was pyrosequenced.

PMID- 29571282
TI  - A triple co-culture method to investigate the effect of macrophages and
      fibroblasts on myoblast proliferation and migration.
AB  - The communication between nonmyogenic cells, such as macrophages and fibroblasts,
      and myoblasts is crucial for successful skeletal muscle repair. In vitro co
      culture methods can be used to increase our understanding of these cellular
      interactions; however, current protocols are restricted to two, often physically
      separate, cell populations. Here, we demonstrate a novel, inexpensive in vitro
      triple co-culture method that facilitates the co-culture of at least three cell
      populations with some degree of cell-cell contact. Using this method, we
      determined the effect of macrophages and fibroblasts on myoblast proliferation
      and migration. A significant increase in myoblast proliferation and migration was
      observed following co-culture with either macrophages or fibroblasts. However,
      triple co-culture of macrophages, fibroblasts, and myoblasts revealed that the
      presence of macrophages prevented fibroblasts from maintaining this positive
      effect on myoblast migration. Macrophages, on the other hand, continued to
      promote myoblast proliferation whether in the presence of fibroblasts or not. Our
      triple co-culture system highlights the significance of multicellular
      communication in regulating myoblast proliferation and migration and emphasizes
      the importance of more complex co-culture systems when investigating myogenesis
      in vitro.

PMID- 29571283
TI  - Limitations of methods for measuring the concentration of human genomic DNA and
      oligonucleotide samples.
AB  - We compared different methods (absorbance, fluorescent dye-binding, and digital
      PCR) for measuring the concentrations of human genomic DNA from cultured cells
      and absorbance measurements of a synthetic DNA oligonucleotide. NIST Standard
      Reference Material (SRM) 2082, a pathlength absorbance standard, was used to
      benchmark the absorbance measurements done with microvolume spectrophotometers
      and a microvolume plate reader. Control absorbance values were measured on a high
      accuracy spectrophotometer and a NIST calibrated pathlength cuvette. Measurements
      of the human genomic DNA sample were done with several types of fluorescent dye
      binding assays using different DNA calibrators. The fluorescent dye binding
      methods gave different results for genomic DNA depending upon the type of DNA
      calibrator and the fluorescent dye that was used. The human genomic DNA sample
      was also characterized by using six different droplet digital PCR assays
      (amplicons located on different chromosomes) to measure the average copy number.
      Conversion of the digital PCR data to copy numbers was sensitive to the droplet
      size used for calculations and conversion to mass concentration was dependent
      upon the molecular weight of the human genome used for the calculations. The
      results from the different methods were compared and the caveats for each
      measurement method were discussed.

PMID- 29571284
TI  - Detection of nucleic acids with a novel stem-loop primer rolling circle
      amplification technique.
AB  - This paper presents a new rolling circle amplification (RCA) technique using stem
      loop primers (SLP). The technique enables detection of target DNA by either
      linear or exponential amplification (SLP-lRCA and SLP-eRCA) in both liquid and
      solid phases. For solid-phase detection, SLP-eRCA detects nucleic acids in four
      steps: (1) covalently immobilize an array of capture probes (CP) on a solid
      support; (2) hybridize the CP array with the DNA sample; (3) incubate the CP
      array with an RCA reaction containing two SLPs; (4) image the CP array. SLP-eRCA
      detects nucleic acids in liquid phase in one step: a real-time RCA reaction
      containing the DNA sample and two SLPs. Both liquid- and solid-phase detection
      methods employ a general rolling circle and an SLP. The other SLP is specific to
      the target. The technique was verified by detecting synthesized oligonucleotides
      and six different human papillomaviruses (HPVs), both in liquid phase and on a
      solid surface. The technique also detected two high-risk HPVs (HPV16 and HPV18)
      in cervical carcinoma cells (HeLa and SiHa) and clinical samples. This study
      provides proof-of-concept for the new RCA technique for nucleic acid detection,
      which overcomes major limitations of current RCA approaches.

PMID- 29571285
TI  - A multi-trait Bayesian method for mapping QTL and genomic prediction.
AB  - BACKGROUND: Genomic prediction and quantitative trait loci (QTL) mapping
      typically analyze one trait at a time but this may ignore the possibility that
      one polymorphism affects multiple traits. The aim of this study was to develop a
      multivariate Bayesian approach that could be used for simultaneously elucidating
      genetic architecture, QTL mapping, and genomic prediction. Our approach uses
      information from multiple traits to divide markers into 'unassociated' (no
      association with any trait) and 'associated' (associated with one or more
      traits). The effect of associated markers is estimated independently for each
      trait to avoid the assumption that QTL effects follow a multi-variate normal
      distribution. RESULTS: Using simulated data, our multivariate method (BayesMV)
      detected a larger number of true QTL (with a posterior probability > 0.9) and
      increased the accuracy of genomic prediction compared to an equivalent univariate
      method (BayesR). With real data, accuracies of genomic prediction in validation
      sets for milk yield traits with high-density genotypes were approximately equal
      to those from equivalent single-trait methods. BayesMV tended to select a similar
      number of single nucleotide polymorphisms (SNPs) per trait for genomic prediction
      compared to BayesR (i.e. those with non-zero effects), but BayesR selected
      different sets of SNPs for each trait, whereas BayesMV selected a common set of
      SNPs across traits. Despite these two dramatically different estimates of genetic
      architecture (i.e. different SNPs affecting each trait vs. pleiotropic SNPs),
      both models indicated that 3000 to 4000 SNPs are associated with a trait. The
      BayesMV approach may be advantageous when the aim is to develop a low-density SNP
      chip that works well for a number of traits. SNPs for milk yield traits
      identified by BayesMV and BayesR were also found to be associated with detailed
      milk composition. CONCLUSIONS: The BayesMV method simultaneously estimates the
      proportion of SNPs that are associated with a combination of traits. When applied
      to milk production traits, most of the identified SNPs were associated with all
      three traits (milk, fat and protein yield). BayesMV aims at exploiting
      pleiotropic QTL and selects a small number of SNPs that could be used to predict
      multiple traits.

PMID- 29571286
TI  - Refining a major QTL controlling spotted wilt disease resistance in cultivated
      peanut (Arachis hypogaea L.) and evaluating its contribution to the resistance
      variations in peanut germplasm.
AB  - BACKGROUND: Spotted wilt, caused by tomato spotted wilt virus (TSWV), has been
      one of major diseases in cultivated peanut grown in the southeastern United
      States (US) since 1990. Previously a major quantitative trait locus (QTL)
      controlling spotted wilt disease resistance was mapped to an interval of 2.55 cM
      genetic distance corresponding to a physical distance of 14.4 Mb on chromosome
      A01 of peanut by using a segregating F2 population. The current study focuses on
      refining this major QTL region and evaluating its contributions in the US peanut
      mini-core germplasm. RESULTS: Two simple sequence repeat (SSR) markers associated
      with the major QTL were used to genotype F5 individuals, and 25 heterozygous
      individuals were selected and developed into an F6 segregating population. Based
      on visual evaluation in the field, a total of 194 susceptible F6 individuals were
      selected and planted into F7 generation for phenotyping. Nine SSR markers were
      used to genotype the 194 F6 individuals, and QTL analysis revealed that a
      confidence interval of 15.2 Mb region had the QTL with 22.8% phenotypic variation
      explained (PVE). This QTL interval was further genotyped using the Amplicon-seq
      method. A total of 81 non-redundant single nucleotide polymorphism (SNP) and
      eight InDel markers were detected. No recombinant was detected among the F6
      individuals. Two InDel markers were integrated into the linkage group and helped
      to refine the confidence interval of this QTL into a 0.8 Mb region. To test the
      QTL contributes to the resistance variance in US peanut mini-core germplasm, two
      flanking SSR markers were used to genotype 107 mini-core germplasm accessions. No
      statistically significant association was observed between the genotype at the
      QTL region and spotted wilt resistance in the mini-core germplasm, which
      indicated that the resistance allelic region at this QTL didn't contribute to the
      resistance variance in the US peanut mini-core germplasm, thus was a unique
      resistance source. CONCLUSION: A major QTL related to spotted wilt disease
      resistance in peanut was refined to a 0.8 Mb region on A01 chromosome, which
      didn't relate to spotted wilt disease resistance in the US peanut mini-core
      germplasm and might be a unique genetic source.

PMID- 29571287
TI  - Chronic oxycodone induces axonal degeneration in rat brain.
AB  - BACKGROUND: Chronic opioid therapy for non-malignant pain conditions has
      significantly increased over the last 15 years. Recently, the correlation between
      opioid analgesics and alternations in brain structure, such as
      leukoencephalopathy, axon demyelination, and white matter lesions, has been
      demonstrated in patients with a history of long-term use of prescription opioids.
      The exact mechanisms underlying the neurotoxic effect of opioids on the central
      nervous system are still not fully understood. We investigated the effect of
      chronic opioids using an animal model in which female rats were orally gavaged
      with 15 mg/kg of oxycodone every 24 h for 30 days. In addition we tested
      oxycodone, morphine and DAMGO in breast adenocarcinoma MCF7 cells, which are
      known to express the MU-opioid receptor. RESULTS: We observed several changes in
      the white matter of animals treated with oxycodone: deformation of axonal tracks,
      reduction in size of axonal fascicles, loss of myelin basic protein and
      accumulation of amyloid precursor protein beta (beta-APP), suggesting axonal
      damages by chronic oxycodone. Moreover, we demonstrated activation of pro
      apoptotic machinery amid suppression of anti-apoptotic signaling in axonal tracks
      that correlated with activation of biomarkers of the integrated stress response
      (ISR) in these structures after oxycodone exposure. Using MCF7 cells, we observed
      induction of the ISR and pro-apoptotic signaling after opioid treatment. We
      showed that the ISR inhibitor, ISRIB, suppresses opioid-induced Bax and CHOP
      expression in MCF7 cells. CONCLUSIONS: Altogether, our data suggest that chronic
      opioid administration may cause neuronal degeneration by activation of the
      integrated stress response leading to induction of apoptotic signaling in neurons
      and also by promoting demyelination in CNS.

PMID- 29571288
TI  - Bone markers and cardiovascular risk in type 2 diabetes patients.
AB  - BACKGROUND: Vascular calcifications are associated with a three- to fourfold
      increased risk of cardiovascular disease (CVD) and are highly prevalent in type 2
      diabetes patients. Emerging evidence indicates that vascular calcification is a
      process of active bone formation regulated by stimulators and inhibitors of
      calcification. Therefore, this study aimed to evaluate whether six bone markers
      are associated with CVD risk in patients with type 2 diabetes. METHODS: We used
      data of a case-cohort study, nested in the EPIC-NL cohort, comprising 134 CVD
      cases and a random subcohort of 218 participants, all with type 2 diabetes at
      baseline. Six bone markers (osteocalcin, osteopontin, osteonectin,
      osteoprotegerin, alkaline phosphatase and sclerostin) were measured in baseline
      plasma samples with multiplex assays and information on CVD events was obtained.
      The association of bone makers with CVD risk was evaluated using Cox proportional
      hazard analyses. RESULTS: Higher concentrations of plasma osteopontin were
      associated (ptrend < 0.01) with an increased CVD risk with a hazard ratio of 2.00
      (95%-CI 1.20-3.35) for the highest versus the lowest quartile in a multivariable
      adjusted model. The other bone markers were not associated with CVD risk.
      CONCLUSIONS: Higher osteopontin concentrations were associated with an increased
      CVD risk in type 2 diabetes patients. No consistent associations were found for
      the other five bone markers and risk of CVD in type 2 diabetes patients.

PMID- 29571289
TI  - Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal
      formulations exhibit enhanced synergistic antitumor efficacy.
AB  - BACKGROUND: The systemic administration of cytotoxic chemotherapeutic agents for
      cancer treatment often has toxic side effects, limiting the usage dose. To
      increase chemotherapeutic efficacy while reducing toxic effects, a rational
      design for synergy-based drug regimens is essential. This study investigated the
      augmentation of therapeutic effectiveness with the co-administration of
      paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and
      curcumin (CUR; a chemosensitizer) in an MCF-7 cell line. RESULTS: We optimized
      niosome formulations in terms of surfactant and cholesterol content. Afterward,
      the novel cationic PEGylated niosomal formulations containing Tween-60:
      cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to
      serve as a model for better transfection efficiency and improved stability. The
      optimum formulations represented potential advantages, including extremely high
      entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth
      surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both
      CUR and PTX), sustained release, small diameter (~ 90 nm for both agents),
      desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX
      kinetic release could be adequately fitted to the Higuchi model. A threefold and
      3.6-fold reduction in CUR and PTX concentration was measured, respectively, when
      the CUR and PTX was administered in nano-niosome compared to free CUR and free
      PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the
      combination treatment of CUR and PTX was particularly effective in enhancing the
      cytotoxicity activity against MCF-7 cells. CONCLUSIONS: Most importantly, CUR and
      PTX, in both free form and niosomal forms, were determined to be less toxic on
      MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate
      that the combination therapy of PTX with CUR using the novel cationic PEGylated
      niosome delivery is a promising strategy for more effective breast cancer
      treatment.

PMID- 29571290
TI  - Exercise capacity in diabetes mellitus is predicted by activity status and
      cardiac size rather than cardiac function: a case control study.
AB  - BACKGROUND: The reasons for reduced exercise capacity in diabetes mellitus (DM)
      remains incompletely understood, although diastolic dysfunction and diabetic
      cardiomyopathy are often favored explanations. However, there is a paucity of
      literature detailing cardiac function and reserve during incremental exercise to
      evaluate its significance and contribution. We sought to determine associations
      between comprehensive measures of cardiac function during exercise and maximal
      oxygen consumption ([Formula: see text]peak), with the hypothesis that the
      reduction in exercise capacity and cardiac function would be associated with co
      morbidities and sedentary behavior rather than diabetes itself. METHODS: This
      case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and
      10 healthy controls age/sex-matched to each diabetes subtype] performing
      cardiopulmonary exercise testing and bicycle ergometer echocardiography studies.
      Measures of biventricular function were assessed during incremental exercise to
      maximal intensity. RESULTS: T2DM subjects were middle-aged (52 +/- 11 years) with
      a mean T2DM diagnosis of 12 +/- 7 years and modest glycemic control (HbA1c 57 +/-
      12 mmol/mol). T1DM participants were younger (35 +/- 8 years), with a 19 +/- 10
      year history of T1DM and suboptimal glycemic control (HbA1c 65 +/- 16 mmol/mol).
      Participants with T2DM were heavier than their controls (body mass index 29.3 +/-
      3.4 kg/m2 vs. 24.7 +/- 2.9, P = 0.001), performed less exercise (10 +/- 12 vs. 28
      +/- 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see
      text]peak = 26 +/- 6 vs. 38 +/- 8 ml/min/kg, P < 0.0001). These differences were
      not associated with biventricular systolic or left ventricular (LV) diastolic
      dysfunction at rest or during exercise. There was no difference in weight,
      exercise participation or [Formula: see text]peak in T1DM subjects as compared to
      their controls. After accounting for age, sex and body surface area in a
      multivariate analysis, significant positive predictors of [Formula: see text]peak
      were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while
      T2DM was a negative predictor. These combined factors accounted for 80% of the
      variance in [Formula: see text]peak (P < 0.0001). CONCLUSIONS: Exercise capacity
      is reduced in T2DM subjects relative to matched controls, whereas exercise
      capacity is preserved in T1DM. There was no evidence of sub-clinical cardiac
      dysfunction but, rather, there was an association between impaired exercise
      capacity, small LV volumes and sedentary behavior.

PMID- 29571291
TI  - Factors associated to prevalence and treatment of carbapenem-resistant
      Enterobacteriaceae infections: a seven years retrospective study in three
      tertiary care hospitals.
AB  - BACKGROUND: The increasing incidence of carbapenem-resistant Enterobacteriaceae
      (CRE), has resulted in a difficult problem in the current clinical anti-infective
      treatment. We performed a retrospective analysis of prevalence and treatment for
      CRE infections patients. METHODS: This study was conducted in three tertiary care
      hospitals from January 1, 2010 to December 30, 2016. Baseline data, treatment,
      and outcomes were collected in patients with ventilator-associated bacterial
      pneumonia (VABP), bacteremia, complicated urinary tract infection (cUTI)/acute
      pyelonephritis (AP), hospital-acquired bacterial pneumonia (HABP), superficial
      wound infection (SWI), biliary tract infection (BTI), deep wound infection (DWI)
      and sterile body fluids infection (SBFI) due to CRE. RESULTS: One hundred twenty
      four cases of CRE infection were identified: 31 VABP, 22 bacteremia, 18 cUTI/AP,
      16 HABP, 16 SWI, 9 BTI, 7 DWI and 5 SBFI. The patient population had significant
      immunocompromised (33 of 124, 26.6%) and severe sepsis (43 of 124, 34.7%). The
      most common CRE pathogens were Klebsiella pneumoniae (84 of 124, 67.7%) and
      Enterobacter cloacae (24 of 124, 19.4%). And the production of IMP-type
      carbapenemase was the main antibiotic resistance mechanism. The majority of
      patients to take monotherapy for empiric therapy and dual therapy for direct
      treatment. Outcomes were universally poor (28-day mortality was 22.6%, 28 of 124)
      across all sites of infection. CONCLUSIONS: We identified a large number of cases
      of CRE infection in 7 years from different parts, most of these pathogens have
      been confirmed to produce IMP-type carbapenemases. The retrospective analysis of
      cases of such bacterial infections will help to control future infections of
      these pathogens. Despite the high mortality rate, we still found that the
      selection of quinolone antibiotics can be effective in the treatment of CRE
      producing IMP type enzymes.

PMID- 29571292
TI  - Genetic contexts related to the diffusion of plasmid-mediated CTX-M-55 extended
      spectrum beta-lactamase isolated from Enterobacteriaceae in China.
AB  - BACKGROUND: CTX-M-55 extended-spectrum beta-lactamases are being rapidly
      disseminated and transmitted in clinical practices around the world. The genetic
      contexts of the transferable plasmid-mediated blaCTX-M-55 gene in
      Enterobacteriaceae were detected and characterized in this study. METHODS:
      Isolates were obtained from the First Affiliated Hospital of Zhengzhou University
      between September 2015 and March 2016. Based on polymerase chain reaction and
      BLAST analysis, resistance genes and genetic context of the blaCTX-M-55 gene were
      investigated. Conjugation experiments and multilocus sequence typing were
      performed to demonstrate plasmid-mediated blaCTX-M-55 transmission. RESULTS:
      Thirteen blaCTX-M-55-positive isolates of Enterobacteriaceae were obtained. Seven
      isolates were Escherichia coli, 3 were Klebsiella pneumoniae, 1 was Citrobacter
      freundii, 1 was Morganella morganii and 1 was Serratia marcescens. The blaCTX-M
      55 gene has not previously been identified from C. freundii and M. morganii. Four
      different blaCTX-M-55 genetic contexts were identified, and all of them harbored
      ISEcp1 in the region upstream of blaCTX-M-55 (in two cases, ISEcp1 was truncated
      by IS26, and in one case, it was truncated by IS1294), whereas ORF477 was
      detected downstream of the blaCTX-M-55 gene from 12 of 13 strains. The novel
      genetic context of ISEcp1?-blaCTX-M-55-?IS903 was firstly detected the IS903
      element which was identified downstream of blaCTX-M-55. A conjugation assay
      revealed that all blaCTX-M-55 plasmids were quickly and easily transferable to
      recipient E. coli, which then presented resistance to multiple antibiotics.
      CONCLUSIONS: Numerous blaCTX-M-55-positive strains were isolated in a short
      period of 7 months. The findings indicate that blaCTX-M-55 was rapidly
      disseminated. The genetic context and conjugative transfer found in this study
      demonstrate that there is active transmission of blaCTX-M-55 among strains of
      Enterobacteriaceae in China, which could give rise to an urgent global public
      health threat.

PMID- 29571293
TI  - Biomarkers of endothelial dysfunction predict sepsis mortality in young infants:
      a matched case-control study.
AB  - BACKGROUND: Reducing death due to neonatal sepsis is a global health priority,
      however there are limited tools to facilitate early recognition and treatment. We
      hypothesized that measuring circulating biomarkers of endothelial function and
      integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis
      and predict their clinical outcome. METHODS: We conducted a matched case-control
      (1:3) study of 98 young infants aged 0-59 days of life presenting to a referral
      hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2,
      sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary
      outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).
      RESULTS: Ang-2 concentrations at presentation were higher among infants who
      subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared
      to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who
      died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041),
      and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR
      4.82, p = 0.013). CONCLUSIONS: This study provides new evidence linking the
      Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with
      suspected sepsis. If validated in additional studies, markers of the angiopoietin
      Tie2 axis may have clinical utility in risk stratification of infants with
      suspected sepsis.

PMID- 29571294
TI  - Detection of Neisseria meningitidis in a paediatric patient with septic arthritis
      using multiplexed diagnostic PCR targeting meningitis/encephalitis (ME).
AB  - BACKGROUND: Neisseria meningitidis is associated with meningitis and septicemia.
      Septic meningococcal arthritis is relatively uncommon and its diagnosis
      associated with clinical and microbiological challenges. Early recognition and
      treatment is required to prevent joint destruction. PURPOSE: We describe a case
      of an eleven-year-old boy with septic arthritis and the first reported use of a
      multiplexed diagnostic PCR test, capable of simultaneous rapid detection of 14
      pathogens directly from CSF samples, to determine presence of N. meningitides in
      a synovial fluid sample. RESULTS: In this case, blood cultures and an aspiration
      of the joint fluid were negative for microbial growth, but leucocytes were
      present. Analysis of samples using the multiplexed FilmArray(r)
      meningitis/encephalitis panel (MEP) proved positive for N. meningitidis. In
      parallel, samples forwarded to an accredited reference laboratory confirmed the
      findings by bacterial 16S rRNA gene amplification and sequencing. Subsequent to
      these results, empiric treatment with intravenous flucloxacillin was discontinued
      and oral amoxicillin administered for 1 month. The status of the patient improved
      with etiology-based antimicrobial therapy. CONCLUSIONS: This case demonstrates
      difficulties associated with clinical and microbiological diagnosis of primary
      septic meningococcal arthritis. We describe the first successful use of the
      FilmArray(r) MEP assay in detection of N. meningitidis in that context.

PMID- 29571295
TI  - Comparison of nephrotoxicity of Colistin with Polymyxin B administered in
      currently recommended doses: a prospective study.
AB  - BACKGROUND: The most important concern with polymyxins (Colistin and Polymyxin B)
      use is nephrotoxicity. There is no prospective data comparing nephrotoxicity of
      these two drugs, when administered in high doses and as per current
      recommendations. We conducted a prospective study to compare their trend of
      nephrotoxicity in our patient population. METHODS: Our study included adult ICU
      patients who received more than 48 h of Colistin or Polymyxin B and had no
      confounding factors for nephrotoxicity. Loading and maintenance doses were given
      as per a uniform protocol. Nephrotoxicity was defined as twofold increase in
      serum creatinine, or 50% decrease in estimated baseline creatinine clearance.
      Patients were followed up for 1 week after therapy. Statistical analysis was
      performed using SPSS version 20.0. RESULTS: 61 patients were included in Colistin
      group, and 51 patients in Polymyxin B group. Median Colistin dose was 233.3 (IQR
      150-300) mg/day and median Polymyxin B dose was 200 (IQR 180-240) mg/day. Median
      duration of Colistin and Polymyxin B use was 7 (IQR 5-7) days and 7 (IQR 7-9)
      days respectively. Nephrotoxicity developed in 39.3% patients in Colistin group
      compared to 11.8% patients in Polymyxin B group. Mean onset of nephrotoxicity was
      3.8 +/- 0.8 days with Colistin, and 4.2 +/- 0.7 days with Polymyxin B therapy. In
      bivariate analysis, Colistin daily dose >= 300 mg was found to be associated with
      nephrotoxicity. There was no effect of age or BMI on Colistin toxicity. Mean
      duration of renal failure was 4.9 +/- 3.1 days with Colistin use, and 5.0 +/- 2.4
      days with Polymyxin B use. 75% patients in Colistin group and 83.3% patients in
      Polymyxin B group who developed nephrotoxicity recovered their renal function by
      1 week. CONCLUSIONS: Colistin in currently recommended doses is significantly
      more nephrotoxic than Polymyxin B. Colistin toxicity is dose-dependent, mostly
      mild to moderate, and is reversible in most cases.

PMID- 29571296
TI  - YM155 decreases radiation-induced invasion and reverses epithelial-mesenchymal
      transition by targeting STAT3 in glioblastoma.
AB  - BACKGROUND: Radiotherapy constitutes a standard arm of therapy in the multimodal
      treatment of patients with glioblastoma (GBM). Ironically, studies have recently
      revealed that radiation can augment malignant progression, by promoting migration
      and invasion, which make the disease especially difficult to cure. Here, we
      investigated the anticancer effects of YM155, a purported radiosensitizer, in GBM
      cell lines. METHODS: GBM cell lines U251 and U87 were treated with YM155 to
      assess cytotoxicity and activity of the molecule in vitro. Nude mice were
      implanted with cells to generate orthotopic xenografts for in vivo studies.
      Response of cells to treatment was examined using cell viability,
      immunofluorescence, wound healing, and the Transwell invasion assay. Molecules
      potentially mediating response were examined through western blot analysis,
      phospho-kinase arrays, and qPCR. Cells were transfected with siRNA knockdown and
      gene expression constructs to identify molecular mediators of response. RESULTS:
      YM155 reduced viability of U251 and U87 cells and enhanced radiosensitivity
      through inhibition of homologous recombination. Besides, YM155 decreased invasion
      caused by radiation and led to expression changes in molecular markers associated
      with EMT. STAT3 was one of 10 molecules identified on a phosphokinase array
      exhibiting significant change in phosphorylation under YM155 treatment.
      Transfection with STAT3 siRNAs or expression constructs demonstrated that EMT
      changes were achieved by inhibiting the phosphorylation of STAT3 and were
      survivin-independent. Finally, combining YM155 and radiation in orthotopic
      xenografts reduced growth and prolonged overall survival of animals. CONCLUSIONS:
      YM155 decreased radiation-induced invasion in GBM cell lines in vitro and in vivo
      through inhibition of STAT3.

PMID- 29571297
TI  - Correction to: From IB2 to IIIB locally advanced cervical cancers: report of a
      ten-year experience.
AB  - In the original publication [1] one author name was spelled incorrect.

PMID- 29571298
TI  - Toll-like receptor 3 modulates the behavioral effects of cocaine in mice.
AB  - BACKGROUND: The nucleus accumbens in the midbrain dopamine limbic system plays a
      key role in cocaine addiction. Toll-like receptors (TLRs) are important pattern
      recognition receptors (PPRs) in the innate immune system that are also involved
      in drug dependence; however, the detailed mechanism is largely unknown. METHODS:
      The present study was designed to investigate the potential role of TLR3 in
      cocaine addiction. Cocaine-induced conditioned place preference (CPP), locomotor
      activity, and self-administration were used to determine the effects of TLR3 in
      the rewarding properties of cocaine. Lentivirus-mediated re-expression of Tlr3
      (LV-TLR3) was applied to determine if restoration of TLR3 expression in the NAc
      is sufficient to restore the cocaine effect in TLR3-/- mice. The protein levels
      of phospho-NF-kappaB p65, IKKbeta, and p-IkappaBalpha both in the cytoplasm and
      nucleus of cocaine-induced CPP mice were detected by Western blot. RESULTS: We
      showed that both TLR3 deficiency and intra-NAc injection of TLR3 inhibitors
      significantly attenuated cocaine-induced CPP, locomotor activity, and self
      administration in mice. Importantly, the TLR3-/- mice that received intra-NAc
      injection of LV-TLR3 displayed significant increases in cocaine-induced CPP and
      locomotor activity. Finally, we found that TLR3 inhibitor reverted cocaine
      induced upregulation of phospho-NF-kappaB p65, IKKbeta, and p-IkappaBalpha.
      CONCLUSIONS: Taken together, our results describe that TLR3 modulates cocaine
      induced behaviors and provide further evidence supporting a role for central pro
      inflammatory immune signaling in drug reward. We propose that TLR3 blockade could
      be a novel approach to treat cocaine addiction.

PMID- 29571299
TI  - SUPPA2: fast, accurate, and uncertainty-aware differential splicing analysis
      across multiple conditions.
AB  - Despite the many approaches to study differential splicing from RNA-seq, many
      challenges remain unsolved, including computing capacity and sequencing depth
      requirements. Here we present SUPPA2, a new method that addresses these
      challenges, and enables streamlined analysis across multiple conditions taking
      into account biological variability. Using experimental and simulated data, we
      show that SUPPA2 achieves higher accuracy compared to other methods, especially
      at low sequencing depth and short read length. We use SUPPA2 to identify novel
      Transformer2-regulated exons, novel microexons induced during differentiation of
      bipolar neurons, and novel intron retention events during erythroblast
      differentiation.

PMID- 29571300
TI  - Erythroderma and extensive poikiloderma - a rare initial presentation of
      dermatomyositis: a case report.
AB  - BACKGROUND: Dermatomyositis is a humoral-mediated inflammatory myopathy with
      symmetrical proximal muscle weakness and dermatological manifestations such as
      Gottron's papules, heliotrope rash, periungual abnormalities, and flagellate
      erythema. Erythroderma is a severe and potentially life-threatening
      dermatological condition with diffuse erythema and scaling involving more than
      90% of the skin surface area. Poikiloderma vasculare atrophicans refers to
      mottled hyperpigmentation and hypopigmentation of the skin with in-between
      telangiectases and areas of atrophy and is considered a variant of mycosis
      fungoides. Poikilodermatomyositis is the term given to the condition with
      poikiloderma and inflammatory myopathy. Only a few cases are reported on
      erythroderma in dermatomyositis and poikilodermatomyositis. Erythrodermal pattern
      of dermatomyositis transforming into poikilodermatomyositis is a recognized rare
      manifestation of dermatomyositis and we could find only one case report in the
      literature. CASE PRESENTATION: A 53-year-old Sri Lankan woman presented with
      intermittent fever of 5 months' duration with erythroderma. Later she developed
      progressive, symmetrical proximal muscle weakness. Following a short course of
      small dose steroids, erythroderma settled but changed to extensive poikiloderma
      involving more than 90% of her skin with her face being relatively spared. She
      had an early heliotrope rash, shawl sign, and Gottron papules. Electromyography
      and muscle biopsy were supportive of inflammatory myositis and skin biopsy showed
      evidence of dermatomyositis. Inflammatory markers and muscle enzymes were also
      elevated. Autoimmune antibodies and myositis-specific autoantibodies were
      negative. She was started on orally administered prednisolone 1 mg/kg per day
      with methotrexate 10 mg once a week and had a good response to treatment with
      resolution of the skin condition and improvement of muscle power. Imaging
      studies, endoscopies, and tumor markers did not reveal any malignancy.
      CONCLUSIONS: This case illustrates a rare presentation of dermatomyositis
      initially presenting as fever, erythroderma, and proximal muscle weakness and
      later developing poikiloderma involving more than 90% of the skin. It is
      important to be aware of this rare presentation to avoid misdiagnosis. With the
      currently available literature it is not possible to conclude that erythroderma
      is a bad prognostic factor in dermatomyositis or a predictive factor for a
      malignancy. Patients have a good response to steroids with a combination of
      immunosuppressants.

PMID- 29571301
TI  - Assessment of household ownership of bed nets in areas with and without
      artemisinin resistance containment measures in Myanmar.
AB  - BACKGROUND: Myanmar lies in the Greater Mekong Subregion where there is
      artemisinin-resistant Plasmodium falciparum malaria. As the artemisinin compound
      is the pillar of effective antimalarial therapies, containing the spread of
      artemisinin resistance is a national and global priority. The use of insecticide
      treated bed nets/long-lasting insecticidal nets (ITNs/LLINs) is the key
      intervention for ensuring the reduction of malaria transmission and the spread of
      resistant strains, and for eventually eliminating malaria. This study aimed at
      assessing household ownership of, access to, and utilization of bed nets in areas
      of Myanmar with and without artemisinin resistance containment measures. METHODS:
      Secondary data from a nationwide community-based malaria survey conducted by the
      National Malaria Control Program in 2014 were analyzed. Based on evidence of
      artemisinin resistance, Myanmar was divided into tiers 1, 2, and 3: townships in
      tiers 1 and 2 were aggregated as the Myanmar Artemisinin Resistance Containment
      (MARC) areas and were compared with tier 3 townships, which were defined as non
      MARC areas. The chi-square test was used to compare groups, and the level of
      significance was set at P <= 0.05. RESULTS: Of the 6328 households assessed,
      97.2% in both MARC and non-MARC areas had at least one bed net (any type), but
      only 63% of households had ITNs/LLINs. Only 44% of households in MARC areas and
      24% in non-MARC areas had adequate numbers of ITNs/LLINs (one ITN/LLIN per two
      persons, P <  0.001). Nearly 44% of household members had access to ITNs/LLINs.
      Regarding the utilization of ITNs/LLINs, 45% of household members used them in
      MARC areas and 36% used them in non-MARC areas (P <  0.001, desired target =
      100%). Utilization of ITNs/LLINs among children aged below five years and
      pregnant women (high malaria risk groups) was low, at 44% and 42%, respectively.
      CONCLUSIONS: This study highlights the nationwide shortfalls in the ownership of,
      access to, and utilization of ITNs/LLINs in Myanmar, which is of particular
      concern in terms of containing the spread of artemisinin resistance. It
      highlights the need for priority attention to be paid and mobilization of
      resources in order to improve bed net coverage and utilization through bed net
      distribution and/or social marketing, information dissemination, and awareness
      raising.

PMID- 29571302
TI  - High-Performance Thin-Layer Chromatography Coupled with Electrospray Ionization
      Tandem Mass Spectrometry for Identifying Neutral Lipids and Sphingolipids in
      Complex Samples.
AB  - High-performance thin-layer chromatography was directly combined with
      electrospray mass spectrometry (ESI-MS) for structural identification issues
      below the level of lipid classes in complex samples through a portable,
      automated, elution-based interface. For samples as diverse as biodiesel and human
      plasma, separation conditions using Automated Multiple Development were selected
      in each case to provide lipid classes as zones narrow enough to ensure a direct
      transfer of them to ESI-MS. The respective zone of interest can be selected at
      will. ESI+ spectra of neutral lipids and sphingolipids showed sodium adducts when
      recorded from the plate. By using the described technique and ion-trap
      technology, the respective sodium adducts were fragmented. Sodium remained as the
      charge of the fragment ions and, thus, was useful for their structural
      identification through MSn. In this way, composition profiles of each class by
      ESI+-MS, and further identification of individual lipids and the molecular
      species belonging to each of them, were obtained by MS/MS and/or high-resolution
      MS. Thus, mono and diacylglycerides in ESI+ and fatty acids (in ESI-) were
      identified as low-concentration impurities in a fatty acid methyl ester-based
      biodiesel sample. Likewise, molecular species of sphingomyelins and
      globotriaosylceramides were unequivocally identified in human plasma samples.

PMID- 29571303
TI  - Development and Validation of a Surface Plasmon Resonance Biosensor for Specific
      Detection of Porcine Serum Albumin in Food.
AB  - Food allergies are a potential food safety and public health concern worldwide.
      To assure the safety of people who experience allergic reactions, it is necessary
      to establish effective and reliable methods for rapid detection of food
      allergens. This paper reports an innovative method for the rapid detection and
      analysis of porcine serum albumin (PSA), known as a major allergen in pork, based
      on a surface plasmon resonance (SPR) biosensor. The antibodies known to have a
      high bioactivity against PSA were verified by competitive indirect-ELISA and then
      immobilized on the SPR sensor surface, thus allowing them to capture PSA. The
      developed SPR demonstrated a linear range from 1.0 to 450 ng/mL for the
      measurement of PSA with a detection limit of 19.81 ng/mL. Within-day RSD (1.97
      4.02%) and between-day RSD (1.88-4.15%) were no more than 5%. The SPR was
      evaluated for analysis of six commercial food samples and showed almost perfect
      agreement between the results obtained by ELISA test kits without significant
      differences (P > 0.05). Therefore, this assay permits accurate, specific, and
      sensitive detection of PSA in pork and pork products.

PMID- 29571304
TI  - Ultrasound-Assisted Emulsification Microextraction in an Online System for
      Determination of Cadmium in Water and Tea Samples.
AB  - In this work, a method using ultrasound-assisted emulsification microextraction
      (USAEME) without the use of ligands in an online system for preconcentration and
      determination of cadmium was developed. The method was based on the
      preconcentration of cadmium by USAEME, employing trichloroethylene as the
      extraction solvent, and subsequent retention of the rich phase in a mini-column
      packed with silica gel. The extracted metal was determined by flame atomic
      absorption spectrometry. The parameters that affect the extraction of cadmium
      were optimized using the univariate method. Under optimized conditions, the
      method presented a limit of detection of 0.17 MUg/L, a limit of quantification of
      0.57 MUg/L, an enrichment factor of 56, and a consumptive index of 0.18 mL/min.
      The accuracy of the method was tested by analyzing the certified reference
      material, National Institute of Standards and Technology (NIST) 1573 (tomato
      leaves). The determination of Cd in water (drinking water, bottled water, river
      water, and seawater) and tea (black and green tea) samples was also performed
      using the proposed method. The method is simple, efficient, and eco-friendly
      because it requires low consumption of an organic solvent.

PMID- 29571305
TI  - Determination of Biogenic Amines in Cheese by Ion Chromatography with Tandem Mass
      Spectrometry Detection.
AB  - A new method for determination of underivatized biogenic amines in cheese based
      on ion exchange chromatography coupled with tandem mass spectrometric detection
      was proposed. The method was applied to the analysis of 10 biogenic amines
      (trimethylamine, putrescine, cadaverine, histamine, 2-phenylethylamine, spermine,
      spermidine, tryptamine, agmatine, and tyramine) in different types of cheese. The
      amines were extracted only with water without any additional derivatization step
      or sample cleanup. This is a great advantage in terms of simplicity of sample
      pretreatment procedure compared with other currently existing methods in the
      literature. Biogenic amines were separated using cation exchange column, under
      gradient elution conditions by mixing formic acid (1.00 M) and deionized water.
      Detection was achieved using tandem MS/MS, with the instrument set into multiple
      reaction monitoring mode to ensure high specificity. The detection and
      quantification limits were in the ranges of 12-46 MUg/L and 40-153 MUg/L,
      respectively. The exceptions were spermidine and spermine, with detection limits
      of 0.8 and 5.4 mg/L, respectively. The linearity for most of the biogenic amines
      was from 10 MUg/L up to 10 mg/L. The best recoveries were observed for
      trimethylamine, tyramine, and cadaverine, and were 89, 94, and 102%,
      respectively. The results showed that this method can be used for routine
      determination of biogenic amines in different types of cheeses as well other food
      matrices. It must be stressed that the proposed method is capable of determining
      10 biogenic amines, including tyramine, which is reported to cause food
      intoxication commonly associated with cheeses.

PMID- 29571306
TI  - ?

PMID- 29571307
TI  - [Physical activities adapted to homeless people].
AB  - Around ten homeless people were invited to take part in a programme of physical
      activities to improve their health status. Only motricity and walking pathways
      were followed assiduously for eight weeks. The assessment of the physical
      condition and quality of life showed an improvement in these areas, in particular
      for one of the participants. However, the lack of motivation and assiduity
      remains an obstacle to regular activity.

PMID- 29571308
TI  - [The role of the nurse in supporting smoking cessation].
AB  - A study was carried out in May 2014 of the first 100 patients who came to seek
      help to stop smoking in 2013 with the first contact led by a nurse. A mail
      questionnaire was sent to this group of patients to evaluate their smoking status
      and the nurse's first contact organization. Among 34% respondents, 40% had not
      smoked for at least eight months. Three quarters had found this nursing support
      useful highlighting the added value of a nurse in supporting first contact in the
      smoking cessation process.

PMID- 29571309
TI  - ?

PMID- 29571310
TI  - [Health and environment, prevention or precaution?]
AB  - The health status of the populations of developed countries has never been as
      satisfactory, but will it stay that way? Research on the subject is difficult due
      to the complex interactions between our environment and our health, with risks
      inherent to each noxious agent. Preventing the risks proven to be linked to the
      quality of our living environments is usually the responsibility of authorities,
      but individuals can also adopt precautionary practices.

PMID- 29571312
TI  - [Environmental health education].
AB  - Environmental health education aims to reduce the impact of risk factors for
      patients. The caregiver's role is to adopt a positive education approach with
      concrete ways of controlling the living environment. He or she must support
      people in asserting their choices in terms of health and to make their own
      contribution to reducing risks.

PMID- 29571311
TI  - [Reducing the impacts of hot weather in a context of climate change].
AB  - The impact of climate change on the health of individuals raises fears of
      significant long-term effects. Certain repercussions are already evident. Health
      professionals, particularly those working with vulnerable people, play a key role
      in health promotion and taking into account the challenges posed by hot weather.
      They need to be better trained in order to promote behaviours more favourable to
      health.

PMID- 29571313
TI  - [Environmental health, the patient's point of view and expectations].
AB  - The place which people give to their living environment is dependent on how much
      information they have and their perception of the risks for their health.
      Nowadays, patients are asking more questions regarding outdoor and indoor
      pollution. However, the information they are given is not always sufficient. The
      answers provided by nursing and medical professionals could be complemented by
      information from relevant associations.

PMID- 29571314
TI  - [The role of caregivers in environmental health in hospital].
AB  - Environmental health is part of the daily practice of caregivers in a health
      facility. It is particularly evident in the waste and water quality management
      systems. It is resulting in changes to roles and practices, particularly for
      nurse hygienists.

PMID- 29571315
TI  - [The challenges of sustainable development in healthcare facilities].
AB  - Healthcare and medical-social facilities have a major responsibility within
      society, that of the quality of care, but also that of developing a system of
      sustainable and socially-responsible health. This system must meet the three
      pillars which constitute such an approach: economic, social and environmental
      sustainability. Innovation remains central to the sustainable evolution of
      practices and the first results are now visible.

PMID- 29571316
TI  - [The experience of a health centre undergoing an ecological transition].
AB  - A health centre and its staff have undertaken a sustainable health approach which
      aims to reduce the impact of the environment on health. One of the initiatives
      focused on the improvement of indoor air quality. A change to practices was
      possible thanks to a participative approach, the support of the staff and
      constant communication.

PMID- 29571317
TI  - [The private practice nurse and environmental health].
AB  - Each day in France, more than 110 000 private practice nurses deliver care, in a
      context of the development of early discharge from hospital. Their role in
      environmental health is essential for the patient as well as for the healthcare
      pathway.

PMID- 29571318
TI  - ["The eco-nurse is an expert in environmental health"].
AB  - Eco-nurses are trained in environmental health in order to act as a resource
      person with the public and health professionals. Experts in the field, their
      scope of action is broad, both targeted and on a more global scale. Philippe
      Perrin is an eco-nurse and the director of the Environmental Health Training
      Institute in France.

PMID- 29571319
TI  - ?

PMID- 29571320
TI  - ?

PMID- 29571321
TI  - Alternative therapies in diabetes.

PMID- 29571323
TI  - Correction.

PMID- 29571322
TI  - Long-Term Treatment of Tamoxifen and Raloxifene Alleviates Dystrophic Phenotype
      and Enhances Muscle Functions of FKRP Dystroglycanopathy.
AB  - The third most common form of limb-girdle muscular dystrophies is caused by
      mutations of the Fukutin-related protein (FKRP) gene, with no effective therapy
      available. Selective estrogen receptor modulators, tamoxifen and raloxifene, have
      been widely used for human conditions for their anti-inflammatory, antifibrosis,
      prevention of bone loss, and muscle building effects (essential features for
      muscular dystrophy therapies). We evaluated therapeutic values of tamoxifen and
      raloxifene in FKRPP448L mutant mouse with severe dystrophic phenotype. The mice
      were treated with the drugs for 1 year through daily gavage. We demonstrate that
      tamoxifen and raloxifene significantly ameliorated the disease progression. The
      improvement includes increase in grip force production, extended running time and
      distance in treadmill test, and enhancement in cardiac and respiratory functions.
      Significant reduction in muscle pathology includes diminished fibrosis and fiber
      degeneration. Tamoxifen and raloxifene also significantly mitigated bone loss.
      Tamoxifen, but not raloxifene, caused severe adverse effects on male reproductive
      organs. The results demonstrate that tamoxifen and raloxifene hold significant
      potential for treating FKRP-related muscular dystrophy and probably other
      muscular dystrophies. Sex-related differential effects of the drugs call for a
      careful consideration for the drug and dosage selection in male and female
      patient populations.

PMID- 29571324
TI  - Variations on a Theme by Darwin.
AB  - This Editorial from American Society for Investigative Pathology Executive
      Officer Emeritus, Dr. Mark E. Sobel, reflects on his time serving the society as
      Executive Officer (2001 to 2017).

PMID- 29571327
TI  - Invited Commentary.

PMID- 29571325
TI  - Does the Fuhrman or World Health Organization/International Society of Urological
      Pathology Grading System Apply to the Xp11.2 Translocation Renal Cell Carcinoma?:
      A 10-Year Single-Center Study.
AB  - The Fuhrman and World Health Organization/International Society of Urological
      Pathology (WHO/ISUP) grading systems are widely used to predict survival for
      patients with conventional renal cell carcinoma. To determine the validity of
      nuclear grading systems (both the Fuhrman and the WHO/ISUP) and the individual
      components of the Fuhrman grading system in predicting the prognosis of Xp11.2
      translocation renal cell carcinoma (Xp11.2 tRCC), we identified and followed up
      47 patients with Xp11.2 tRCC in our center from January 2007 to June 2017. The
      Fuhrman and WHO/ISUP grading was reassigned by two pathologists. Nuclear size and
      shape were determined for each case based on the greatest degree of nuclear
      pleomorphism using image analysis software. Univariate and multivariate analyses
      were performed to evaluate the capacity of the grading systems and nuclear
      parameters to predict overall survival and progression-free survival. On
      univariate Cox regression analysis, the parameters of nuclear size were
      associated significantly with overall survival and progression-free survival,
      whereas the grading systems and the parameters of nuclear shape failed to reach a
      significant correlation. On multivariate analysis, however, none of the
      parameters was associated independently with survival. Our findings indicate that
      neither the Fuhrman nor the WHO/ISUP grading system is applicable to Xp11.2 tRCC.
      The assessment of nuclear size instead may be novel outcome predictors for
      patients with Xp11.2 tRCC.

PMID- 29571326
TI  - Identification and Complete Stereochemical Assignments of the New Resolvin
      Conjugates in Tissue Regeneration in Human Tissues that Stimulate Proresolving
      Phagocyte Functions and Tissue Regeneration.
AB  - Resolvin conjugates in tissue regeneration (RCTRs) are new chemical signals that
      accelerate resolution of inflammation, infection, and tissue regeneration.
      Herein, using liquid chromatography-tandem mass spectrometry-based
      metabololipidomics, we identified RCTRs in human spleen, lymph node, bone marrow,
      and brain. In human spleen incubated with Staphylococcus aureus, endogenous RCTRs
      were increased along with conversion of deuterium-labeled docosahexaenoic acid,
      conferring pathway activation. Physical and biological properties of endogenous
      RCTRs were matched with those prepared by total organic synthesis. The complete
      stereochemical assignment of bioactive RCTR1 is 8R-glutathionyl-7S,17S-dihydroxy
      4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, RCTR2 is 8R-cysteinylglycinyl-7S,17S
      dihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, and RCTR3 is 8R-cysteinyl
      7S,17S-dihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid. These
      stereochemically defined RCTRs stimulated human macrophage phagocytosis,
      efferocytosis, and planaria tissue generation. Proteome profiling demonstrated
      that RCTRs regulated both proinflammatory and anti-inflammatory cytokines with
      human macrophages. In microfluidic chambers, the three RCTRs limited human
      polymorphonuclear cell migration. In hind-limb ischemia-reperfusion-initiated
      organ injury, both RCTR2 and RCTR3 reduced polymorphonuclear cell infiltration
      into lungs. In infectious peritonitis, RCTR1 shortened the resolution intervals.
      Each RCTR (1 nmol/L) accelerated planaria tissue regeneration by approximately
      0.5 days, with direct comparison to both maresin and protectin CTRs. Together,
      these results identify a new bioactive RCTR (ie, RCTR3) in human tissues and
      establish the complete stereochemistry and rank-order potencies of three RCTRs in
      vivo. Moreover, RCTR1, RCTR2, and RCTR3 each exert potent anti-inflammatory and
      proresolving actions with human leukocytes.

PMID- 29571329
TI  - Invited Commentary.

PMID- 29571328
TI  - Invited Commentary.

PMID- 29571330
TI  - Chest Wall Mechanics In Vivo With a New Custom-Made Three-Dimensional-Printed
      Sternal Prosthesis.
AB  - PURPOSE: Reconstruction after sternal resection is performed according to surgeon
      intuition; physiologic evidence for selection of prostheses is lacking. We
      present our experience of the in vivo function of a novel device for sternal
      reconstruction. DESCRIPTION: A three-dimensional-printed titanium and porous
      polyethylene sternal prosthesis was made according to the patient's computed
      tomographic scan. The titanium arms slot over adjacent ribs and are fixed in
      place with screws. The porous element allows ingrowth of native tissue while
      preventing lung herniation around the narrow titanium bars. EVALUATION: We
      performed optoelectronic plethysmography to assess the physiologic function of
      the device compared with a muscle flap reconstruction. Asynchronous and
      paradoxical movements of the thoracoabdominal surface were apparent with the
      muscle flap reconstruction but not with the new device. Considerably higher tidal
      volumes and a lower respiratory rate achieved the same minute volume with the new
      device compared with the muscle flap. CONCLUSIONS: Rigid sternal reconstruction
      with a three-dimensional-printed prosthesis demonstrated superior respiratory
      mechanics compared with reconstruction with an autologous muscle flap.

PMID- 29571331
TI  - Hybrid Repair of Kommerell Diverticulum in Right Aortic Arch: Anatomic
      Considerations.

PMID- 29571332
TI  - Reply.

PMID- 29571333
TI  - More Reasons for Pericardiectomy Without Cardiopulmonary Bypass.

PMID- 29571334
TI  - Reply.

PMID- 29571335
TI  - Reply.

PMID- 29571336
TI  - Uniportal Video-Assisted Thoracic Surgery for Pneumothorax: Real Alternative to
      Multiportal?

PMID- 29571337
TI  - Extracorporeal Cardiopulmonary Resuscitation for Refractory Cardiac Arrest
      Deserves Special Consideration.

PMID- 29571338
TI  - Variables Affecting the Heart-Type Fatty Acid Binding Protein Level.

PMID- 29571339
TI  - Right Ventricular Preload and Increased Exercise Performance After Fontan-Bjork
      Modification.

PMID- 29571340
TI  - About Cerebral Protection.

PMID- 29571341
TI  - Correction.

PMID- 29571342
TI  - Is Transplantation Early for the Failing Single Ventricle?

PMID- 29571343
TI  - Decision Making, Evidence, and Practice.

PMID- 29571344
TI  - Graft-Versus-Tumor Effect in Adenocarcinoma of the Lung.
AB  - Donor T cells after allogeneic hematopoietic cell transplantation can give rise
      to the graft-versus-tumor (GVT) effect in hematologic malignancies. GVT effect
      has been reported previously to cause regression of some solid tumors. However,
      none have reported a documented case of GVT effect leading to complete resolution
      of adenocarcinoma of the lung. Here, we present the case of complete regression
      of a pathologically proven adenocarcinoma of the lung in a patient undergoing
      myeloablative-matched unrelated donor peripheral blood stem cell transplantation
      for the treatment of acute myelogenous leukemia.

PMID- 29571345
TI  - Total Artificial Heart as Rescue Therapy for Primary Graft Failure in an Infant.
AB  - An infant unable to be weaned from cardiopulmonary bypass after orthotopic heart
      transplantation was cannulated for extracorporeal membrane oxygenation. During
      the next 3 days, allograft failure and intracardiac thrombosis necessitated
      cardiectomy. To provide acute mechanical circulatory support, artificial atrial
      chambers were constructed with Gore-Tex conduits and PediMag centrifugal pumps
      were connected to each by Berlin Heart EXCOR cannulae. The PediMag pumps were
      subsequently exchanged for 10-mL Berlin Heart EXCOR pumps. After 60 days of
      support by total artificial heart, the patient was bridged successfully to a
      second heart transplant.

PMID- 29571346
TI  - Recurrent Spontaneous Pneumomediastinum With Concurrent Pneumorrhachis: A Rare
      Clinical Entity.
AB  - Spontaneous pneumomediastinum is the presence of interstitial air in the
      mediastinal structures without an apparent cause. Pneumorrhachis is defined as
      the presence of air in the spinal canal. Concurrent pneumorrhachis is an
      extremely rare epiphenomenon of spontaneous pneumomediastinum without
      pneumothorax. Diagnosis is confirmed by radiologic imaging of the chest.
      Spontaneous pneumomediastinum and pneumorrhachis usually resolve with
      conservative therapy such as bed rest, analgesic agents, and supplemental oxygen.
      A 20-year-old male patient presented with recurrent spontaneous pneumomediastinum
      with concurrent pneumorrhachis with a gap of 1 year between the two episodes.
      Pneumomediastinum and pneumorrhachis resolved with conservative management in
      both episodes.

PMID- 29571347
TI  - Salvage Pulmonary Metastasectomy for Local Relapse After Stereotactic Body
      Radiotherapy.
AB  - Although several studies have evaluated the local control and survival outcomes
      in patients undergoing stereotactic body radiotherapy (SBRT) for pulmonary
      oligometastases, little data are available on the management of local relapse.
      Here, we present 3 patients who underwent lobectomy and mediastinal lymph node
      dissection as salvage pulmonary metastasectomy for local relapse after SBRT. The
      postoperative course has been uneventful for all 3 patients, with no evidence of
      disease at 40, 51, and 6 months from the salvage metastasectomy. Our experience
      suggests that salvage pulmonary metastasectomy may be associated with local
      control and long-term survival in carefully selected patients.

PMID- 29571348
TI  - First Surgical Melody Valve-In-Valve Implantation for Early Degeneration in
      Mitral Position.
AB  - Congenital mitral valve disease is a real challenge in infants and small
      children. The implantation of expandable stented valves in mitral position has
      become one of the options of choice in consideration of their acceptable short
      term expandable durability and subsequent feasibility of balloon expansion of
      these devices. We report the first case of a surgical Melody valve-in-valve
      procedure for early Melody valve degeneration in the mitral position. The result
      was good, and the procedure safe, rapid, and without an increased risk when a
      mechanical valve implantation will be necessary.

PMID- 29571349
TI  - Two Cases of Surgical Management of Supravalvular Aortic Stenosis in Familial
      Hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia is a rare autosomal dominant disorder
      caused by gene mutations of the low-density lipoprotein receptor, generally
      characterized by three major signs-hyper low-density lipoprotein cholesterolemia,
      tendon/skin xanthomas, and premature atherosclerosis disease-beginning in
      childhood and including supravalvular aortic stenosis. To the best of our
      knowledge, only a few successful surgical cases for supravalvular aortic stenosis
      in these patients have been reported. We report two cases of homozygous familial
      hypercholesterolemia with severe supravalvular aortic stenosis and coronary
      artery disease associated with very small aortic root, managed by aortic root
      replacement concomitant with coronary artery bypass graft surgery, which resulted
      in excellent postoperative outcomes.

PMID- 29571350
TI  - Elastic-Stable Chest Repair: Costal Plate Fixation for Sternotomy Nonunion.
AB  - Sterile sternotomy nonunion is a recognized complication after median sternotomy.
      It is defined as sternotomy that persists after 3 months without evidence of bony
      healing but with healing of the overlying soft tissues. It is a morbid condition
      associated with pain and sternal instability. We present two challenging cases of
      sterile sternotomy nonunion after cardiac operations that were treated
      successfully with novel methods adopted from the Elastic Stable Chest Repair for
      complex pectus deformity repair, using transverse costal to costal external
      cortical plates and bicortical screws, after debridement, autologous bone
      grafting and double loop wire sternal approximation.

PMID- 29571351
TI  - Tricuspid Valve Repair of Idiopathic Papillary Muscle Rupture.

PMID- 29571352
TI  - Artificial polymer materials debris characteristics along the Moroccan
      Mediterranean coast.
AB  - A monitoring program was carried out in autumn 2015 along the Mediterranean coast
      of Morocco, at sites including urban, village and remote/rural beaches.
      Artificial Polymer Materials (APM) represented 70.64% of all collected items and
      included plastic (16 categories), foamed plastic (3) and other APM materials (2).
      Plastic items represented the dominant debris with 5356 items, i.e. 94.53% of all
      APM debris, foamed plastics presented 191 items (i.e. 3.37%) and other APM summed
      119 items, i.e. 2.1% of all APM. Urban areas presented 49.63% of all APM
      recollected items with cigarette butts representing 32% of total APM items.
      Village areas presented 40.43% of total APM recollected items with cigarette
      butts representing 14.1%. Remote and rural beaches recorded 9.94% of total APM
      items and no cigarette butts were observed. Despite the efforts of local
      administrations, which introduced litter bins and enforced mechanical and manual
      cleaning operations, debris were essentially related to beachgoers.

PMID- 29571353
TI  - Aerosol concentrations and atmospheric dry deposition fluxes of nutrients over
      Daya Bay, South China Sea.
AB  - Based on one and a half years of observations (September 2015 to March 2017) in
      Daya Bay, we analysed the nutrient concentrations in aerosols and calculated dry
      deposition fluxes of nutrients. DON was the dominant species of TDN in aerosol
      particles, accounting for 63.3%. The mean values of DIP, DOP and DSi were 0.78,
      0.61 and 2.6 nmol.m-3, respectively. The mean fluxes of nutrients (TDN, TDP and
      DSi) from dry deposition during the field observation were 2150, 7.4 and 28.2
      MUmol.m-2.month-1, respectively. The fluxes of nitrogen species show a seasonal
      pattern with higher input in spring and winter. The dry deposition of nutrients
      accounted for approximately 20% of the total deposition budget. The molar ratios
      of DIN/DIP in the dry deposition (mean value 167) suggest that atmospheric dry
      deposition of nutrients may increase the risk of the unbalanced nutrient
      condition in the seawater column of Daya Bay.

PMID- 29571354
TI  - Distribution of hydrocarbons in seabed sediments derived from tsunami-spilled oil
      in Kesennuma Bay, Japan.
AB  - As a result of the 2011 Great East Japan earthquake, about 11,000kL of fuel oil
      was spilled into Kesennuma Bay, Miyagi Prefecture. This oil either accumulated in
      seabed sediments or was burned in a marine fire on the sea surface. We
      investigated spatial and temporal variations in the concentrations of oil and
      hydrocarbons. The maximum concentrations of n-hexane extract (NHE), total
      petroleum hydrocarbon (TPH), and polycyclic aromatic hydrocarbons (PAHs) in the
      sediments in 2012 were 8000, 1200, and 16.2mg/kg (DW), respectively. NHE and TPH
      concentrations were high in the inner and west bay, and PAHs concentrations were
      high in the east bay. NHE and PAH concentrations didn't change; however, TPH
      concentrations decreased significantly with time. The total NHE in the sediment
      across the whole bay was estimated at 1685kL and there was still about 13% of the
      original amount in the sediment in December 2014.

PMID- 29571355
TI  - Composition and abundance of marine debris stranded on the beaches of Sri Lanka:
      Results from the first island-wide survey.
AB  - This study provides the first assessment of marine debris washed ashore on 22
      beaches along the coast of Sri Lanka. There was an average of 4.1 large (>25 mm)
      and 158 small (5-25 mm) pieces of debris per square meter of beach. Classified by
      use, packaging material (55%) dominated the debris, followed by consumer products
      (25%) and fishing gear (20%). In terms of materials, plastic was the greatest
      contributor (93%) to marine debris. Beaches near a river mouth or city and those
      with a barrier had greater debris accumulations. The east coast had significantly
      greater small debris density, possibly due to strong northeastern monsoon
      currents. Large spatial heterogeneity was observed in the amount of debris. Long
      term monitoring is imperative to better understand the temporal changes in, and
      the pathways and possible management of, marine debris.

PMID- 29571356
TI  - Contamination level, chemical fraction and ecological risk of heavy metals in
      sediments from Daya Bay, South China Sea.
AB  - Contamination level, chemical fraction and ecological risk of heavy metals in
      sediments from Daya Bay (DYB) were conducted in this study. The results revealed
      that the concentration of Cr, Cu, Zn, As, Cd and Pb in sediments were in the
      range of 36.38-90.33, 9.54-61.32, 33.54-207.33, 7.80-18.43, 0.13-0.43 and 15.89
      30.01 mg kg-1, respectively, with bioavailable fractions of 13.29, 54.16, 47.60,
      32.74, 68.14, 26.59%, respectively. A modified potential ecological risk index
      (MRI) was used for the ecological risk assessment, with ecological risk
      contribution ratios of 75.73, 14.29, 5.47, 1.74, 1.57 and 1.21% for Cd, As, Cu,
      Cr, Pb and Zn, respectively. The main contaminants were Cd and As, with their
      ecological risks "High" and "Moderate" levels, and their enrichment degrees
      "Moderately Severe" and "Moderate", respectively. The multivariate statistical
      analysis suggested that the various anthropogenic activities along the bay might
      contribute mainly to the heavy metals contamination in DYB.

PMID- 29571357
TI  - Modeling of PCB trophic transfer in the Gulf of Lions; 3D coupled model
      application.
AB  - 3D coupled modeling approach is used for the PCB dispersion assessment in the
      Gulf of Lion and its transfer to zooplankton via biogeochemical processes. PCB
      budgets and fluxes between the different species of PCB: dissolved, particulate,
      biosorbed on plankton, assimilated by zooplankton, which are governed by
      different processes: adsorption/desorption, bacteria and plankton mortality,
      zooplankton excretion, grazing, mineralization, volatilization have been
      estimated. Model outputs were compared with the available in situ data. It was
      found that the Rhone River outflows play an important role in the organism
      contamination in the coastal zone, whereas the atmospheric depositions are rather
      more important in the offshore zones. The transfer of the available contaminant
      to bacteria and phytoplankton species is mainly related to the biomass present in
      the water column. Absorption fluxes (grazing) to zooplankton are rather higher
      than the passive sorption fluxes, which are themselves also linked to the
      sorption coefficient.

PMID- 29571358
TI  - Changes in mercury exposure of marine birds breeding in the Gulf of Maine, 2008
      2013.
AB  - Mercury is a potent contaminant that can disrupt an organism's behavior and
      physiology, ultimately affecting reproductive success. Over the last 100 years,
      environmental deposition of anthropogenic sourced mercury has increased globally,
      particularly in the U.S. Northeast region. Marine birds are considered effective
      bioindicators of ecosystem health, including persistent marine contaminants.
      Goodale et al. (2008) found that mercury exposure exceeded adverse effects levels
      in some marine bird species breeding across the Gulf of Maine. We re-examined
      mercury contamination in four species identified as effective bioindicators.
      Compared with the previous sampling effort, inshore-feeding species showed
      significant increases in mercury exposure, while one pelagic-feeding species
      remained stable. This suggests that a major shift may have occurred in
      methylmercury availability in inshore waters of the Gulf of Maine. Understanding
      environmental mercury trends in the Gulf of Maine, and its significance to marine
      birds and other taxa will require a dedicated, standardized, long-term monitoring
      scheme.

PMID- 29571359
TI  - Collected marine litter - A growing waste challenge.
AB  - Marine litter, in particular plastic debris, poses a serious threat to marine
      life, human health and the economy. In order to reduce its impact, marine litter
      collections such as beach clean-ups are frequently conducted. This paper presents
      a systematic review of temporal developments, geographical distribution,
      quantities and waste treatment pathways of collected marine litter. Results from
      over 130 studies and projects highlight the worldwide increase in collection
      efforts. Many of these are in wealthy countries that do not primarily contribute
      to the problem. Over 250 thousand tonnes, have already been removed, but there is
      little or no information available regarding how this waste is treated or used
      post collection. This paper highlights the need for a whole-system quantitative
      assessment for the collection and waste treatment of marine litter, and
      identifies the challenges associated with utilising this waste in the future.

PMID- 29571360
TI  - First assessment of the effectiveness of the international convention on the
      control of harmful anti-fouling systems on ships in Tunisia using imposex in
      Hexaplex trunculus as biomarker.
AB  - The global ban on the use of tributyltin (TBT) forced in September 2008 was
      ratified in Tunisia as late as June 2011. In this context, the present study aims
      to highlight the consequences of TBT contamination by monitoring 22 Tunisian
      sites before (2007) and after the ban (2012 and 2016) using as biomarker the
      occurrence of imposex in Hexaplex trunculus. From 2004 to 2016, complete recovery
      from imposex was reported in 11 sites. All average imposex indices calculated for
      each sampling year also decreased: imposex incidence from 61 to 27%, VDSI from 2
      to 0.7, and RPLI from 15.7 to 1.6%. Ecological Quality Ratios (EQR) revealed that
      the sampling sites are in moderate to good ecological status. Overall, the
      present study confirms the effectiveness of the enacted legislation in reducing
      the impact of TBT pollution along the Tunisian coast.

PMID- 29571361
TI  - Macrophytes as bioindicators of heavy metal pollution in estuarine and coastal
      environments.
AB  - The Derwent estuary, in Tasmania (Australia), is highly contaminated with heavy
      metals with significant levels in both sediments and benthic fauna. However,
      little is known about metal content in benthic primary producers. We
      characterized metal content (Arsenic, Cadmium, Copper, Lead, Selenium and Zinc)
      in twelve species of macrophyte, including red, green, and brown algae, and
      seagrasses, from the Derwent. The metals, arsenic, copper, lead, and Zinc were
      detected in all of the macrophytes assessed, but the levels differed between
      species. Seagrasses accumulated the highest concentrations of all metals; with Zn
      levels being particularly high in the seagrass Ruppia megacarpa (from the upper
      Estuary) and Pb was detected in Zostera muelleri (from the middle estuary). Ulva
      australis was ubiquitous throughout the middle-lower estuary and accumulated Zn
      in relatively high concentrations. The findings suggest that analysis of multiple
      species may be necessary for a comprehensive understanding of estuary-wide metal
      pollution.

PMID- 29571362
TI  - Beach litter and woody-debris colonizers on the Atlantico department Caribbean
      coastline, Colombia.
AB  - Some marine invertebrates can inhabit floating substrates, and raft over long
      distances, becoming a significant environmental problem in terms of alien species
      and habitat disruption. On the Atlantico Department beaches (Colombia) woody
      debris and plastic litter dominate (86%) the types of refuse on the beaches with
      their densities ranging from 0.82-1.72 items m-1. Such litter and woody debris
      generate the optimal conditions for floating colonizers. In this work, 26 beaches
      were surveyed, and 16 of them (62%) were found to have marine fauna using litter
      and woody debris as a substrate for potential rafting and dispersal. Serpulidae
      polychaete tubes, goose barnacles Lepas (Anatifa) anserifera Linnaeus, 1767, and
      the bryozoans Arbopercula tenella (Hincks, 1880), Arbopercula angulata (Levinsen,
      1909), plus three unidentified species were found colonizing woody debris, seeds,
      plastic and glass bottles. These findings of woody debris and litter facilitating
      the arrival and dispersal of non-native species on this coast, demonstrate that
      preventive management of such refuse in coastal habitats goes beyond simply
      preserving coastal esthetics.

PMID- 29571364
TI  - Biodegradation of hexadecane using sediments from rivers and lagoons of the
      Southern Gulf of Mexico.
AB  - The Southern Gulf of Mexico is an area highly impacted by crude oil extraction,
      refining activities and the presence of natural petroleum seepage. Oceanic
      currents in the Gulf of Mexico continually facilitate the transport of
      hydrocarbons to lagoons and rivers. This research evaluated hexadecane (HXD)
      degradation in marine sediment samples from lagoons and rivers that are fed by
      the Southern Gulf of Mexico, specifically six samples from rivers, three samples
      from lagoons, and one sample from a marine outfall. The highest rates of
      biodegradation were observed in sediments from the mouths of the Gonzalez River
      and the Champoton Lagoon. The lowest consumption rate was found in sediment from
      the mouth of the Coatzacoalcos River. With regards to the Ostion Lagoon and the
      Grijalva River, there was a low rate of consumption, but a high efficiency of
      degradation which took place at the end of the experiments. No correlation was
      found between the consumption rate and the environmental physicochemical
      parameters.

PMID- 29571363
TI  - Risk assessment of some heavy metals in mussels (Mytilus galloprovincialis) and
      veined rapa whelks (Rapana venosa) for human health.
AB  - The purpose of the present study was to analyze the concentrations of lead,
      cadmium and mercury in mussels (Mytilus galloprovincialis) and veined rapa whelks
      (Rapana venosa) caught in the Varna Bay of Black Sea and to evaluate the risk for
      human health from the presence of the three heavy metals. The highest average
      concentrations in mussels were those of cadmium (0.280 mg/kg), followed by lead
      (0.251 mg/kg) and mercury (0.017 mg/kg). Veined rapa whelks also showed highest
      levels of cadmium (1.113 mg/kg), followed by lead (0.045 mg/kg) and mercury
      (0.034 mg/kg). EDI values for adults consuming mussels and veined rapa whelks
      were below the published RfDo and PTWI values. All THQ and HI values were below
      1. The consumption of M. galloprovincialis and R. venosa caught in the Varna Bay,
      Black Sea, did not pose any risk for the health of adult people as lead, cadmium
      and mercury were concerned.

PMID- 29571365
TI  - Organochlorine pesticide accumulation in seabirds and marine mammals from the
      Northwest Pacific.
AB  - Bioaccumulation of organochlorine pesticides by marine organisms is one of the
      methods of environmental quality. Concentrations of organochlorine pesticides
      (HCH isomers (alpha-, beta-, gamma-HCH), p,p'-DDT and its metabolites (p,p'-DDD,
      p,p'-DDE)) in samples of seabirds (Northern fulmar Fulmarus glacialis, Crested
      auklet Aethia cristatella, Auklet-crumb Aethia pusilla, Pacific gull Larus
      schistisagus, and Gray petrel Oceanodroma furcate) and marine mammals (Gray
      whales Eschrichtius robustus and Pacific walrus Odobenus rosmarus divergens) were
      measured by a GC-MS. The total concentration of OCPs in mammals was higher than
      in seabirds. Environmental biomonitoring with the use of seabirds and marine
      mammals, as a long-lived species, is used for global monitoring, since
      bioaccumulation in these organisms occurs throughout life. The environmental
      assessment of the Northwest Pacific marine ecosystems revealed that the levels of
      OCP contamination in this area are similar to the other subarctic regions of the
      World Ocean.

PMID- 29571366
TI  - Ecophysiological and metabolic responses to interactive exposure to nutrients and
      copper excess in the brown macroalga Cystoseira tamariscifolia.
AB  - Global scenarios evidence that contamination due to anthropogenic activities
      occur at different spatial-temporal scales, being important stressors:
      eutrophication, due to increased nutrient inputs; and metal pollution, mostly
      derived from industrial activities. In this study, we investigated
      ecophysiological and metabolic responses to copper and nutrient excess in the
      brown macroalga Cystoseira tamariscifolia. Whole plants were incubated in an
      indoor system under control conditions, two levels of nominal copper (0.5 and
      2.0MUM), and two levels of nutrient supply for two weeks. Maximal quantum yield
      (Fv/Fm) and maximal electron transport rate (ETRmax) increased under copper
      exposure. Photosynthetic pigments and phenolic compounds (PC) increased under the
      highest copper levels. The intra-cellular copper content increased under high
      copper exposure in both nutrient conditions. C. tamariscifolia from the Atlantic
      displayed efficient metal exclusion mechanisms, since most of the total copper
      accumulated by the cell was bound to the cell wall.

PMID- 29571367
TI  - Microplastic in two South Carolina Estuaries: Occurrence, distribution, and
      composition.
AB  - Here we report on the distribution of microplastic contamination in two developed
      estuaries in the Southeastern United States. Average concentration in intertidal
      sediments of Charleston Harbor and Winyah Bay, both located in South Carolina,
      U.S.A., was 413.8 +/- 76.7 and 221.0 +/- 25.6 particles/m2, respectively. Average
      concentration in the sea surface microlayer of Charleston Harbor and Winyah Bay
      was 6.6 +/- 1.3 and 30.8 +/- 12.1 particles/L, respectively. Concentration in
      intertidal sediments of the two estuaries was not significantly different (p =
      0.58), however, Winyah Bay contained significantly more microplastics in the sea
      surface microlayer (p = 0.02). While microplastic concentration in these
      estuaries was comparable to that reported for other estuaries worldwide,
      Charleston Harbor contained a high abundance of black microplastic fragments
      believed to be tire wear particles. Our research is the first to survey
      microplastic contamination in Southeastern U.S. estuaries and to provide insight
      on the nature and extent of contamination in these habitats.

PMID- 29571368
TI  - Sensitivity of indicators matters when using aggregation methods to assess marine
      environmental status.
AB  - The sensitivity of the 15 indicators included in a complex aggregation method
      (Nested Environmental status Assessment Tool), applied to a case study in the
      Caspian Sea in Iran, has been studied to discriminate between areas impacted and
      non-impacted by bathing activities. Two methods were used: (i) the 15 indicators
      were grouped into four groups (physicochemical, bacteria, plankton, and benthos)
      and each group was investigated separately (one-way sensitivity analysis),
      calculating NEAT values after omitting each group independently; and (ii)
      indicators were selected randomly, using 1000 Monte Carlo iterations, and
      removing from 1 to 14 indicators at each iteration. The results revealed that the
      abundance of Pontogammarus was the single indicator that made the difference in
      assessing the status among locations, differentiating bathing and non-bathing
      areas. Hence, this indicator is regarded as a monitoring element detecting the
      impacts produced by a management measure (beach nourishment) taken by the
      authorities to maintain the bathing activity.

PMID- 29571369
TI  - Comparative analysis of trace element accumulation in seagrasses Posidonia
      oceanica and Cymodocea nodosa: Biomonitoring applications and legislative issues.
AB  - This study aimed to compare the bioaccumulation patterns and translocation of
      trace elements (As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) from the environment in the
      seagrasses Posidonia oceanica and Cymodocea nodosa. Results showed that P.
      oceanica has a higher capacity of accumulation. P. oceanica and C. nodosa
      accumulate mainly in roots and leaves, the main organs acting as potential
      bioindicators. No significant correlation was found between water and both
      seagrasses. In turn, P. oceanica and C. nodosa were correlated, to a different
      extent, with As, Cd, Cu, Ni and Zn in sediments. This study showed also that
      current European regulations do not provide an exhaustive set of legal
      concentration limits of trace elements in marine water and sediments. Seagrasses
      P. oceanica and C. nodosa can act as effective bioindicators of trace elements
      only if quality limits are set for the most toxic elements present in marine
      ecosystems.

PMID- 29571370
TI  - Biomarkers of physiological responses of Octopus vulgaris to different coastal
      environments in the western Mediterranean Sea.
AB  - The increase of pollutants in coastal seawater could produce several harmful
      biological effects on marine organisms related to the production of reactive
      oxygen species (ROS) causing cellular and tissue damages through oxidative stress
      mechanisms. Common octopuses (Octopus vulgaris) inhabiting coastal areas under
      high anthropogenic activity of Mallorca (W-Mediterranean Sea) have the ability to
      control oxidative damage by triggering antioxidant enzyme responses. Analyzing
      the digestive glands, octopuses from human-altered coastal areas showed higher
      activity of superoxide dismutase (SOD), catalase (CAT) and glutathione S
      transferase (GST) compared to octopuses from non-influenced coastal waters (i.e.
      marine reserve area). Higher metallothionein (MT) concentrations and lack of
      malondialdehyde (MDA) variations also reflect adaptations of O. vulgaris to
      polluted areas. This is the first study assessing the levels of the oxidative
      stress biomarkers on O. vulgaris in the Mediterranean Sea, revealing their
      usefulness to assess diverse environmental pollution effects on this relevant
      ecological and commercial species.

PMID- 29571371
TI  - Liver histopathology and biochemical biomarkers in Gobius niger and Zosterisessor
      ophiocephalus from polluted and non-polluted Tunisian lagoons (Southern
      Mediterranean Sea).
AB  - The aim of this study was to appraise the response of a multi-marker approach in
      fish species, Gobius niger and Zosterisessor ophiocephalus, in a polluted lagoon
      (Bizerte lagoon: MB and ML sites) and in a reference site (Ghar-El-Melh lagoon
      entrance) by the analysis of physiological indexes, liver histopathology and some
      biochemical biomarkers. The results showed liver hypertrophy in fish collected
      from Bizerte lagoon as well as many non-specific lesions, unlike the reference
      site. All Bizerte lagoon sites had the same prevalence of histopathological
      lesions, but the mean intensity (MI) of parasites seemed to be more sensible as
      an indicator of pollution levels. Indeed, parasite MI was more important in MB
      site that has a higher pollution level. Also, biochemical biomarkers showed an
      induction in Bizerte lagoon sites with some differences within sites and species.
      The impact of the continuous release of pollution on the biomarker's response is
      discussed.

PMID- 29571372
TI  - Limited impact of beach nourishment on macrofaunal recruitment/settlement in a
      site of community interest in coastal area of the Adriatic Sea (Mediterranean
      Sea).
AB  - Beach nourishment is a widely utilized solution to counteract the erosion of
      shorelines, and there is an active discussion on its possible consequences on
      coastal marine assemblages. We investigated the impact caused by a small-scale
      beach nourishment carried out in the Western Adriatic Sea on macrofaunal
      recruitment and post-settlement events. Artificial substrates were deployed in
      proximity of nourished and non-manipulated beaches and turbidity and
      sedimentation rates were measured. Our results indicate that sedimentation rates
      in the impacted site showed a different temporal change compared to the control
      sites, suggesting potential modifications due to the beach nourishment. The
      impact site was characterized by subtle changes in terms of polychaete abundance
      and community structure when compared to controls, possibly due to beach
      nourishment, although the role of other factors cannot be ruled out. We conclude
      that small-scale beach nourishments appear to be an eco-sustainable approach to
      contrast coastal erosion.

PMID- 29571373
TI  - Trace elements concentrations in squids consumed in Shandong Province China and
      their associated risks to the human health.
AB  - Determination of ten metal levels in 160 squid samples caught from offshore and
      the oceanic fishing locations by ICP-MS was made. The mean metal concentration in
      the squid muscles decreasing in the order of: Zn, Fe, Cu, As, Mn, Se, Cd, Pb, Cr
      and Ni. Metal concentrations in the squids were assessed for human uses according
      to provisional tolerable weekly intake (PTWI) and provisional tolerable daily
      intake (PTDI).The estimated hazard quotients for the individual metals from
      squids were found in accordance to the following sequence: As > Cd > Cu > Se > Cr
      > Zn > Pb > Fe > Mn > Ni, with the greatest hazard upon human health coming
      primarily from As (1.34 < HQ < 1.73 in the Loliginidae from two offshore sampling
      sites and the Humboldt squid from the eastern Pacific Ocean). In regards to the
      heavy metal pollution of the coastal sea areas, the squids captured from offshore
      sites might pose a higher potential health risk to consumers compared to those
      from the ocean.

PMID- 29571374
TI  - Shifts in phytoplankton community structure in response to hydrological changes
      in the shallow St Lucia Estuary.
AB  - Hydrological regimes are key in shaping the structure of phytoplankton
      communities in estuaries. Because anthropogenic disturbances often alter the
      quantity and quality of riverine inputs, this research focused on investigating
      phytoplankton dynamics in the St. Lucia Estuary, since being reconnected to the
      Mfolozi River. Due to the closed mouth state of the estuary, the input from the
      river resulted in oligohaline (>=5) conditions and the characteristic reverse
      salinity gradient to persist throughout the study (i.e. one year). Model results
      indicated that phytoplankton communities were structured by rainfall, light
      transmittance and depth, while shifts between dominant groups were driven by
      salinity and flow season. The persistence of chlorophytes and euglenophytes as
      the co-dominant functional group indicates the freshening and nutrient-enriched
      nature of the river. This study provides the first detailed account documenting
      the response of the phytoplankton community to recent restoration efforts in the
      St Lucia Estuary, a Ramsar Site.

PMID- 29571375
TI  - Historical trends of perfluoroalkyl substances (PFASs) in dated sediments from
      semi-enclosed bays of Korea.
AB  - Information is scarce on historical trends of perfluoroalkyl substances (PFASs)
      in the coastal environment. In this study, four sediment cores were collected
      from semi-enclosed bays of Korea to investigate the pollution history,
      contamination profiles, and environmental burden of PFASs. The total PFAS
      concentrations in sediment cores ranged from 6.61 to 821 pg/g dry weight. The
      highest concentrations of PFASs were found in surface or sub-surface sediments,
      indicating on-going contamination by PFASs. Historical trends in PFASs showed a
      clear increase since the 1980s, which was consistent with the global PFAS
      consumption pattern. Concentrations of PFASs were dependent on the organic carbon
      content in sediment cores. PFOS and longer-chain PFASs were predominant in all of
      the sediment cores. In particular, a large proportion of longer-chain PFASs was
      observed in the upper layers of the sediment cores from industrialized coastal
      regions. Inventories and fluxes estimated for PFASs were similar to those for
      PCDD/Fs.

PMID- 29571376
TI  - Comparison of pollution indices for the assessment of heavy metals in the
      sediments of seaports of NSW, Australia.
AB  - Sediments samples from six seaports of NSW, Australia were analysed for the
      presence of metal contamination. Geoaccumulation index (Igeo), enrichment factor
      (EF), pollution load index (PLI), potential ecological risk (PER) and sediment
      pollution index (SPI) along with multivariate statistical analysis were used to
      identify the pollution pattern and possible sources of metals in the ports. The
      results demonstrate Cu, Pb and Zn pollution (Igeo > 5) at most sites and
      enrichment of As, Ni, Mn (EF > 3) and other metals. The PER recommends serious
      pollution at Port Kembla and Eden. By contrast, PLI and SPI demonstrate high
      contamination in all ports with exception of Port Botany and Yamba. PCA and
      cluster analysis detected major groups of elements in which three distinct
      clusters of pollutants and sites were apparent by dendrogram which portray simple
      and effective baseline scenarios for port activity-related quality assessment of
      surface sediments.

PMID- 29571378
TI  - ALEX index enables detection of alien macroalgae invasions across habitats within
      a marine protected area.
AB  - A modified version of the ALien Biotic IndEX (ALEX) has been recently proposed to
      evaluate biological invasions in macroalgal assemblages. ALEX was applied in a
      Marine Protected Area where a recreational-fishing port is present testing the
      following hypotheses: ALEX increases with the distance from the port, it changes
      between the two directions off the port and it changes among three different
      habitats: Cystoseira beds, algal turf and dead matte of the seagrass Posidonia
      oceanica. A total of 78 native macroalgal taxa and 4 introduced species were
      found, the Chlorophyta Caulerpa cylindracea and the Rhodophyta Apoglossum
      gregarium, Acrothamnion preissii and Womersleyella setacea. All study sites were
      in high quality status highlighting that the assemblages investigated were at an
      early stage of NIS invasion. However, ALEX detected different values among
      conditions and habitats within the MPA, suggesting a local dynamics of NIS spread
      and different resistance to invasion of the investigated habitats.

PMID- 29571377
TI  - Surveillance of human enteric viruses in coastal waters using concentration with
      methacrylate monolithic supports prior to detection by RT-qPCR.
AB  - This is the first surveillance study using methacrylate monolithic supports to
      concentrate environmental coastal water samples, prior to molecular target
      detection by RT-qPCR. Rotaviruses (RoV) and Noroviruses (NoV) were monitored in a
      polluted area at the Bay of Koper (Gulf of Trieste, Northern Adriatic Sea) and at
      a nearby bathing area and mussel farm areas. RoV and NoV are released into the
      Bay of Koper, with higher rates close to the discharge of the wastewater
      treatment plant, however, they can be detected at recreational and mussel farming
      areas. Our results showed that water bodies considered safe based on FC
      concentrations, can still have low, yet potentially infective, concentrations of
      human viruses.

PMID- 29571379
TI  - Cost effective and practically viable oil spillage mitigation: Comprehensive
      study with biochar.
AB  - Biochar is carbonaceous mass that is produced from pyrolysis or gasification of
      biomass. It is so far majorly explored for soil remediation application, but
      recently it has attracted a lot of interest because of its unexplored
      applications in the area of adsorption. In this work, detailed study on biochars
      produced from two different feeds (rice husk and saw dust), at two different
      temperatures (450 and 550 degrees C) and two different rates (fast and slow) of
      pyrolysis are discussed for oil spill mitigation. Biochar is characterized in
      detail by various techniques such as FTIR, 13C CPMAS, FESEM, RAMAN, TGA to
      determine the structural composition and observe the extent of pyrolysis. Tests
      to assess the performance of produced biochars as sorbents for oil spill
      mitigation have been demonstrated. The as produced biochars selectively absorbed
      crude oil from oil/water biphasic mixtures in various capacities.

PMID- 29571380
TI  - Inorganic arsenic causes apoptosis cell death and immunotoxicity on European sea
      bass (Dicentrarchus labrax).
AB  - Inorganic arsenic (As) is one of the most toxic pollutants in the water. We have
      studied their effects on the marine teleost European sea bass (Dicentrarchus
      labrax) at 2 and 10 days of 5 MUM of As2O3 (sub-lethal doses) waterborne
      exposure. Arsenic accumulates in liver and gill tissues. The expression profile
      of five genes (bax, blc2, casp3, casp8 and casp9) involved in apoptosis cell
      death confirmed apoptotic effects in liver, slight changes in gill and no effects
      in skin according with the histopathology findings. Total IgM level and
      peroxidase activities were increased at 2 and 10 days, respectively. The
      bactericidal activity was decreased at 2 days after As exposure. A general
      decrease of cellular immune activities with significant differences in the case
      of respiratory burst activity was observed after 2 and 10 days of exposure. This
      work describes for the first time the effects of As exposure on European sea
      bass.

PMID- 29571381
TI  - A modeling approach for reposition dynamics of litter composition in coastal
      areas of the city of Santos, Sao Paulo, Brazil.
AB  - Given the complexity of the dynamics in litter reposition, our objective was
      modeling the possible main and interaction effects of tidal oscillations, seasons
      of the year and the moon phases over the solid waste in Santos beaches. A total
      of 80 collections were carried out using quadrat sampling, from which we
      classified, counted and weighed all residue items. We fitted mixed Hurdle models
      to the output datasets and performed hypotheses tests based on this framework. We
      found plastic to be the most abundant residue in all seasons, moon phases and
      tides, followed by Styrofoam and wood. Our models suggest the strongest effect
      was due to seasonal variations, which, in turn, may be related to different human
      activities. Although the dynamics of different components showed independency of
      all interaction structures, plastics depended on the interaction of tide and
      season, whose impact over estuarine life and ecosystem services shall be further
      investigated.

PMID- 29571382
TI  - Marine pollution in the Libyan coastal area: Environmental and risk assessment.
AB  - A comprehensive assessment of the potential adverse effects on environment and
      human health generated by the inputs of chemicals from the most important Libyan
      petrochemical plant is presented. Ecotoxicological risk associated with the
      presence of As, Hg, Ni, Zn and PAHs in marine sediments is low or moderate, with
      a probability of toxicity for ecosystem <9% and <20% for heavy metals and PAHs
      respectively. However, surface sediments result strongly enriched in Hg and As of
      anthropogenic origin. Investigation of metals in fish allowed to assess potential
      risks for human populations via fish intake. Target hazard quotients values
      indicate potential risk associated to toxic metals exposure by fish consumption
      and lifetime cancer risk (TR) values highlight a potential carcinogen risk
      associated to As intake. Noteworthy, the presented results provide an
      unprecedented environmental dataset in an area where the availability of field
      data is very scant, for a better understanding of anthropogenic impacts at
      Mediterranean scale.

PMID- 29571383
TI  - Beach litter along various sand dune habitats in the southern Adriatic (E
      Mediterranean).
AB  - Marine litter accumulates on sandy beaches and is an important environmental
      problem, as well as a threat to habitat types that are among the most endangered
      according to EU legislation. We sampled 120 random plots (2 * 2 m) in spring 2017
      to determine the distribution pattern of beach litter along the zonation of
      habitat types from sea to the inland. The most frequent litter items were
      plastic, polystyrene and glass. A clear increase of litter cover along the sea
      inland gradient is evident, and foredunes and pine forests have the highest cover
      of litter. Almost no litter was present in humid dune slacks. Shoreline and
      recreational activities are the major source of beach litter, while
      ocean/waterway activities are more important in the aphytic zone and strandline.

PMID- 29571384
TI  - Spatial and vertical distribution of radiocesium in seawater of the East China
      Sea.
AB  - The 137Cs activity in surface water of the East China Sea (ECS) was 0.66-1.36 Bq
      m-3 during May of 2011. The low activities were observed in the Changjiang
      Estuary and Zhejiang-Fujian coast and high activities were observed in the south
      offshore and Kuroshio Current pathway, suggesting that the influence from the
      current system in the ECS. The 134Cs were undetectable (<0.03 Bq m-3) and the
      contribution of the Fukushima accident to ECS is estimated to be below 3%; hence
      it is negligible during the investigation period. Using the vertical profiles of
      137Cs in the ECS, the mass balance is obtained, which suggests that the oceanic
      input dominates the 137Cs source in the ECS. 137Cs is potentially useful to trace
      water mass movement in the ECS. Our study provides comprehensive baseline of
      137Cs in the ECS for evaluation of the possible influence of the nuclear power
      plants in the future.

PMID- 29571385
TI  - Plastic ingestion by Tristram's Storm-petrel (Oceanodroma tristrami) chicks from
      French frigate shoals, Northwestern Hawaiian Islands.
AB  - This study provides the first quantification of plastic ingestion in the
      Tristram's Storm-petrel (Oceanodroma tristrami) in over 20 years. We found 100%
      plastic incidence in 57 chicks collected opportunistically over four breeding
      seasons (2007, 2010, 2011, 2012), with the mass of ingested plastic per
      individual ranging from 0.1 to 2.8 g (<=3.3% adult mass). While plastic occurred
      in every bird we examined, the proventriculus contained significantly more
      plastic, more fragments, and larger fragments than the gizzard. Most of the
      ingested plastic (97.5% by mass) consisted of fragments, ranging in length from
      0.4 to 11.6 mm and ranging in surface area from 0.07 to 45.21 mm2. While
      fragments were ubiquitous, occurring in every proventriculus and gizzard we
      analyzed, Tristram's Storm-petrels also ingested foam, line and sheets. Digital
      analysis of 1425 ingested plastic fragments documented a wide range of colors,
      involving shades of white, yellow, orange, red, blue, green, and black.

PMID- 29571386
TI  - What is the best endpoint for assessing environmental risk associated with
      acidification caused by CO2 enrichment using mussels?
AB  - Carbon capture and storage is a technology that has been widely determined to be
      one of the best choices for the short-term reduction of atmospheric CO2
      emissions. The aim of this study was to analyze the effects of CO2 enrichment in
      the ocean on the mussel species Mytilus galloprovincialis using three different
      endpoints: mortality, embryo-larval development, and neutral red retention time
      assays (NRRT). Acute effects were found to be associated with a pH values of 6.0
      while citotoxity effects and embryo-larval development were associated with a pH
      value of 7.0. The NRRT assay and embryo-larval development can be recommended as
      good endpoints for assessing the environmental risk associated with acidification
      by CO2 enrichment because they provide sensitive responses on the effects of
      changes in seawater pH on mussels in a short period of time. Moreover, this study
      may support policymakers in finding appropriate solutions for the conservation of
      marine ecosystems.

PMID- 29571387
TI  - Occurrence of Ostreopsis lenticularis (Dinophyceae: Gonyaulacales) from the
      Archipielago de Revillagigedo, Mexican Pacific.
AB  - From December 2016 to May 2017, 22 phytoplankton surface samples were collected
      with a 20-MUm mesh net at three islands of the Archipielago de Revillagigedo
      (Partida, Socorro and San Benedicto), Mexican Pacific. The sites depth was
      approximately 20-80 m; the surface water temperature was 21-27  degrees C. The
      potentially toxic benthic dinoflagellate Ostreopsis lenticularis was present in
      all the samples. Cells had a lenticular to broadly oval shape, 65-100 MUm long
      and 50-80 MUm wide. The taxonomy of the genus Ostreopsis has been unclear due to
      equivocal ascribing some taxonomic features among species. The identification of
      specimens from the archipelago was made based on the most important taxonomic
      characteristics: the thecal plates, the presence of two types of thecal pores
      (larger and smaller), and the lack of cingulum undulation. The studied cells are
      compared with O. cf. siamensis, O. labens and O. marina. This is the first record
      of the species in the archipelago waters.

PMID- 29571388
TI  - Fake news.

PMID- 29571389
TI  - Elemental concentration and potential ecological risk assessment of reef
      associated surface sediments of Appa Island, Gulf of Mannar Biosphere Reserve,
      Southeast coast of India.
AB  - Thirty three surface sediments were collected for the present study to assess the
      elemental concentration and its associated ecological risk in the reef associated
      surface sediments, Appa Island, Gulf of Mannar Biosphere Reserve, South east
      coast of India. The distribution of calcium carbonate in the reef sediments is
      controlled by coral debris and shell fragments whereas the Organic matter (OM)
      content are chiefly derived from mangroves and sea grasses. The circulation of
      trace elements and Fe, Mn are controlled by the fluvial process and re-suspended
      sediments. The concentration of Pb was primarily controlled by migration of
      pollutants through long shore sediment transport process. The main source of Pb
      in the study area is from coal incinerating power plants and coal handling
      operations from harbors.

PMID- 29571390
TI  - A UAV and S2A data-based estimation of the initial biomass of green algae in the
      South Yellow Sea.
AB  - Previous studies have shown that the initial biomass of green tide was the green
      algae attaching to Pyropia aquaculture rafts in the Southern Yellow Sea. In this
      study, the green algae was identified with unmanned aerial vehicle (UAV), an
      biomass estimation model was proposed for green algae biomass in the radial sand
      ridge area based on Sentinel-2A image (S2A) and UAV images. The result showed
      that the green algae was detected highly accurately with the normalized green-red
      difference index (NGRDI); approximately 1340 tons and 700 tons of green algae
      were attached to rafts and raft ropes respectively, and the lower biomass might
      be the main cause for the smaller scale of green tide in 2017. In addition, UAV
      play an important role in raft-attaching green algae monitoring and long-term
      research of its biomass would provide a scientific basis for the control and
      forecast of green tide in the Yellow Sea.

PMID- 29571391
TI  - Enhancing passive sampling tools for detecting marine bioinvasions.
AB  - Early detection is important for successful management of invasive species, but
      optimising monitoring systems to detect multiple species from different taxonomic
      groups remains a major challenge. Settlement plates are often used to monitor non
      indigenous marine species (NIMS) associated with vessel biofouling, but there
      have been few assessments of their fitness-for-purpose. We deployed arrays of
      settlement plates ("settlement arrays") containing combinations of treatments
      that reflected conditions associated with the vessel transport pathway (i.e.,
      copper based antifouling coatings, shaded habitat) to determine the treatment
      combinations that maximised NIMS diversity. Horizontal (shaded) treatments
      preferentially sampled higher NIS diversity than vertical plates. Although plates
      with copper-based biocides had larger proportions of NIS to indigenous species,
      they sampled only a subset of NIS diversity. Overall diversity was greatly
      enhanced through use of multiple treatments, demonstrating benefits of multi
      faceted sampling arrays for maximising the potential taxonomic and species
      richness.

PMID- 29571392
TI  - Distributions of particulate and dissolved phosphorus in aquatic habitats of
      Peninsular Malaysia.
AB  - Particulate phosphorus was the dominant phosphorus species and accounted for 72
      +/- 5% of total phosphorus in coastal habitats, 63 +/- 4% in estuaries, 58 +/- 6%
      in lakes and 80 +/- 7% in aquaculture farms whereas dissolved inorganic
      phosphorus (DIP) and dissolved organic phosphorus (DOP) were minor components.
      Correlation analyses (DIP vs Chl a; R2 = 0.407, df = 31, p < 0.001) suggested
      phosphorus limiting conditions in lakes, which was corroborated with the highest
      alkaline phosphatase activity (APA) that fluctuated from 0.38 to 41.14 nmol L-1
      min-1. In contrast, APA was elevated in coastal habitats and estuaries only when
      DIP concentration decreased below 0.9 MUM. Moreover size-fractionation experiment
      showed that the highest APA was detected in the 0.2-2 MUm pico-size fraction. Our
      results suggested that the main APA in coastal habitats and estuaries was from
      phototrophic pico-eukaryotes and heterotrophic bacteria, and regulated largely by
      DIP availability.

PMID- 29571393
TI  - Sedimentary mercury (Hg) in the marginal seas adjacent to Chinese high-Hg
      emissions: Source-to-sink, mass inventory, and accumulation history.
AB  - We comprehensively investigated sedimentary Hg in Yellow and East China Seas
      (YECSs), which constitute potentially important depocenters for large
      anthropogenic Hg emissions from mainland China. A large dataset of Al-TOC-Hg
      concentrations led to an in-depth understanding of sedimentary Hg in the entire
      YECSs, including distribution and its determinants, source-to-sink, background
      levels, inventory in flux and budget, and accumulation history. Especially, the
      net atmospheric Hg flux to the sediments was estimated to be 1.3 * 10-5 g/m2/yr,
      which corresponded reasonably well to that calculated using a box model. About
      21.2 tons of atmospheric Hg (approximately 4% of the total anthropogenic
      atmospheric Hg emissions from China) were buried annually in the YECS basin. This
      result implies that most of atmospheric Hg from China is transferred to the
      surface of the Pacific (including the East/Japan Sea and South China Sea) by the
      westerlies and, consequently, can play a critical role in open-sea aquatic
      ecosystems.

PMID- 29571394
TI  - Evidence of marine debris usage by the ghost crab Ocypode quadrata (Fabricius,
      1787).
AB  - Sandy beaches are sites of marine debris stranding, but the interaction of beach
      biota with waste is poorly studied. The objective of this study was to
      investigate whether the ghost crab Ocypode quadrata selects marine debris by
      types using a non-destructive method on sandy beaches of Southeastern Brazil. We
      found marine debris in 7% of 1696 surveyed burrows, and the ghost crabs
      selectivity was mainly by soft plastic (30%), straw (11%), rope (6%) and foam
      (4%). Burrows with marine debris showed higher occupation rate (~68%) compared to
      burrows without debris (~28%), indicating that these materials may increase the
      capacity of ghost crabs to memorize their burrows placement (homing). The
      percentage of marine debris was not always related to their amount in the drift
      line, but ghost crabs used more debris near urbanized areas. Future studies
      should test whether ghost crabs are using marine debris for feeding, homing or
      other mechanisms.

PMID- 29571395
TI  - The contaminant legacy from historic coastal landfills and their potential as
      sources of diffuse pollution.
AB  - Prior to modern environmental regulation landfills in low-lying coastal
      environments were frequently constructed without leachate control, relying on
      natural attenuation within inter-tidal sediments to dilute and disperse
      contaminants reducing environmental impact. With sea level rise and coastal
      erosion these sites may now pose a pollution risk, yet have received little
      investigation. This work examines the extent of metal contamination in saltmarsh
      sediments surrounding a historic landfill in the UK. Patterns of sediment metal
      data suggest typical anthropogenic pollution chronologies for saltmarsh sediments
      in industrialised nations. However, many metals were also enriched at depth in
      close proximity to the landfill boundary and are indicative of a historical
      leachate plume. Though this total metal load is low, e.g., c. 1200 and 1650kg Pb
      and Zn respectively, with >1000 historic landfills on flood risk or eroding
      coastlines in the UK this could represent a significant, yet under-investigated,
      source of diffuse pollution.

PMID- 29571396
TI  - Monitoring of Polycyclic Aromatic Hydrocarbons (PAHs) in Scottish Deepwater
      environments.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were measured in environmental samples
      (sponges, fish and sediment) collected in 2014 and 2016 from the Faroe-Shetland
      Channel and Rosemary Bank Seamount. These data could be used to provide a
      baseline against which any changes can be assessed in the event of an oil spill
      and contribute to any environmental impact assessment. Concentrations in all
      samples were low, often below the detection limits, and were typical of reference
      sites. Sponges can be used as an alternative indicator species to mussels for
      monitoring PAHs in the marine environment as they can accumulate PAHs from both
      the dissolved and particulate phase. PAH concentrations in marine sponges from
      Scottish waters have not previously been reported. Concentrations were low, but
      contained a higher proportion of heavier 4- to 6-ring PAHs compared to the fish
      samples.

PMID- 29571397
TI  - A simple Bird Sensitivity to Oil Index as a management tool in coastal and marine
      areas subject to oil spills when few biological information is available.
AB  - This study sought to develop a simple index for ranking birds' environmental
      sensitivity to oil in which birds are used as biological indicators. The study
      area consisted of both the Santos Estuarine System (SES), and the Laje de Santos
      Marine State Park (LSMSP), located in Southeastern Brazil. Information on the
      bird species and their feeding and nesting behaviors were obtained from the
      literature and were the basis of the sensitivity index created. The SES had a
      higher number of species, but only about 30% were found to be highly sensitive.
      The LSMSP presented a much lower number of species, but all of them were
      considered to be highly sensitive to oil. Due to its simplicity, this index can
      be employed worldwide as a decision-making tool that may be integrated into other
      management tools, particularly when robust information on the biology of birds is
      lacking.

PMID- 29571398
TI  - Microplastics in a wind farm area: A case study at the Rudong Offshore Wind Farm,
      Yellow Sea, China.
AB  - Despite the rapid construction of offshore wind farms, the available information
      regarding the risks of this type of development in terms of emerging pollutants,
      particularly microplastics, is scarce. In this study, we quantified the level of
      microplastic pollution at an offshore wind farm in the Yellow Sea, China, in
      2016. The abundance of microplastics was 0.330 +/- 0.278 items/m3 in the surface
      water and 2.58 +/- 1.14 items/g (dry) in the sediment. To the best of our
      knowledge, the level of microplastic pollution in our study area was slightly
      higher than that in coastal areas around the world. The microplastics detected in
      the surface waters and sediments were mainly fibrous (75.3% and 68.7%,
      respectively) and consisted of some granules and films. The microplastics in the
      samples might originate from garments or ropes via wastewater discharge. The
      abundance of plastic in the water and sediment samples collected from the wind
      farm area was lower than that in the samples collected from outside the wind farm
      area. The anthropogenic hydrodynamic effect was the main factor affecting the
      local distribution of microplastics. The presence of a wind farm could increase
      the bed shear stress during ebb tide, disturbing the bed sediment, facilitating
      its initiation and transport, and ultimately increasing the ease of washing away
      the microplastics adhered to the sediment. This study will serve as a reference
      for further studies of the distribution and migration of microplastics in coastal
      zones subjected to similar marine utilization.

PMID- 29571399
TI  - Effects of corresponding and non-corresponding contaminants on the fate of
      sulfonamide and quinolone resistance genes in the Laizhou Bay, China.
AB  - The environmental behaviors and migration patterns of antibiotic resistance genes
      (ARGs) have attracted considerable research interest. However, there has been
      little research concerning the effects of corresponding and non-corresponding
      contaminants on the fate of ARGs in coastal environments. In the present study,
      the distribution of intI1, sul1, sul2, qnrS and aac(6')-Ib were analyzed in water
      and sediment samples of Laizhou Bay in the context of corresponding and non
      corresponding contaminants. The abundance of intI1, sul1 and sul2 genes exhibited
      a clear decreasing trend extending from the inner estuary to the coastal area.
      Strong and positive correlations existed between sul1/sul2 and sulfonamide
      antibiotic residues in sediments, and between the abundances of intI1 and
      sul1/sul2. Statistical analyses indicated that non-corresponding contaminants
      were partially correlated with ARG abundances. These results suggest that non
      corresponding contaminants may have direct or indirect influences on the
      abundances of ARGs and intI1 in the Laizhou Bay.

PMID- 29571400
TI  - Temporal changes in benthic macrofauna on the west coast of Norway resulting from
      human activities.
AB  - Quantitative analyses of soft bottom invertebrate fauna from four Norwegian sill
      fjords show increased macrofaunal abundance, species richness, and a considerably
      changed benthic deep water macrofaunal composition in the inner parts of the
      fjord system. In retrospect, the analyses show significantly altered benthic
      macrofaunal community structure that was not reflected by the changes in the
      Shannon-Wiener diversity indices during regular monitoring. The observed changes
      are mainly due to an increased abundance of opportunistic species, especially of
      the polychaete Polydora sp. during the last 10-15 years which is correlated
      significantly to declining dissolved oxygen, rising temperature in the bottom
      water and increasing total organic matter in the sediment. Possible anthropogenic
      and climatic impact factors related to the observed macrofaunal changes and
      environmental consequences of the changes are discussed.

PMID- 29571401
TI  - Locating fish bomb blasts in real-time using a networked acoustic system.
AB  - Results are presented of a demonstration of real-time fish blast location in
      Sabah, Malaysia using a networked hydroacoustic array based on the ShotSpotter
      gunshot location system. A total of six acoustic sensors - some fixed and others
      mobile - were deployed at ranges from 1 to 9 km to detect signals from controlled
      test blasts. This allowed the blast locations to be determined to within 60 m
      accuracy, and for the calculated locations to be displayed on a map on designated
      internet-connected computers within 10 s. A smaller three-sensor system was then
      installed near Semporna in Eastern Sabah that determined the locations of
      uncontrolled blasts set off by local fishermen. The success of these
      demonstrations shows that existing technology can be used to protect reefs and
      permit more effective management of blast fishing activity through improved
      detection and enforcement measures and enhanced community engagement.

PMID- 29571402
TI  - Determining light stress responses for a tropical multi-species seagrass
      assemblage.
AB  - Existing mitigations to address deterioration in water clarity associated with
      human activities are based on responses from single seagrass species but may not
      be appropriate for diverse seagrass assemblages common to tropical waters. We
      present findings from a light experiment designed to determine the effects of
      magnitude and duration of low light on a mixed tropical seagrass assemblage.
      Mixed assemblages of three commonly co-occurring Indo-West Pacific seagrasses,
      Cymodocea serrulata, Halodule uninervis and Halophila ovalis were grown in
      climate-controlled tanks, where replicate pots were subjected to a gradient in
      light availability (0.9-21.6 mols PAR m-2 day-1) for 12 weeks. Increased shading
      resulted in declines in growth and changes in cellular and photosynthesis
      responses for all species, although time-scale and magnitude of response were
      species-specific. Applying management criteria (e.g. thresholds) relevant to one
      species may under- or over-estimate potential for impact on other species and the
      meadow as a whole.

PMID- 29571403
TI  - Intertidal geothermal hot springs as a source of trace elements to the coastal
      zone: A case study from Bahia Concepcion, Gulf of California.
AB  - We investigated the influence of the intertidal geothermal hot spring (GHS) on
      the biogeochemistry of trace elements in Santispac Bight, Bahia Concepcion (Gulf
      of California). The geothermal fluids were enriched in As and Hg mainly in ionic
      form. The suspended particulate matter of the GHS had elevated enrichment factor
      (EF) >1 of As, Bi, Cd, Co, Cu, Mn, Mo, Sb, Sn, Sr, Ti, U and Zn. The sediment
      core from GHS1 had high concentration of As, Hg, Corg, S, V, Mo, and U and the
      extremely high EF of these elements at 8cm of the core. The maximum
      bioaccumulation of As and Hg was in seaweeds Sargassum sinicola collected near
      the GHS2. The results confirm the input of trace elements to the coastal zone in
      Bahia Concepcion from geothermal fluids and the evident modification of the
      chemical composition of the adjacent marine environment.

PMID- 29571404
TI  - Effects of sub-seabed CO2 leakage: Short- and medium-term responses of benthic
      macrofaunal assemblages.
AB  - The continued rise in atmospheric carbon dioxide (CO2) levels is driving climate
      change and temperature shifts at a global scale. CO2 Capture and Storage (CCS)
      technologies have been suggested as a feasible option for reducing CO2 emissions
      and mitigating their effects. However, before CCS can be employed at an
      industrial scale, any environmental risks associated with this activity should be
      identified and quantified. Significant leakage of CO2 from CCS reservoirs and
      pipelines is considered to be unlikely, however direct and/or indirect effects of
      CO2 leakage on marine life and ecosystem functioning must be assessed, with
      particular consideration given to spatial (e.g. distance from the source) and
      temporal (e.g. duration) scales at which leakage impacts could occur. In the
      current mesocosm experiment we tested the potential effects of CO2 leakage on
      macrobenthic assemblages by exposing infaunal sediment communities to different
      levels of CO2 concentration (400, 1000, 2000, 10,000 and 20,000 ppm CO2),
      simulating a gradient of distance from a hypothetic leakage, over short-term (a
      few weeks) and medium-term (several months). A significant impact on community
      structure, abundance and species richness of macrofauna was observed in the short
      term exposure. Individual taxa showed idiosyncratic responses to acidification.
      We conclude that the main impact of CO2 leakage on macrofaunal assemblages occurs
      almost exclusively at the higher CO2 concentration and over short time periods,
      tending to fade and disappear at increasing distance and exposure time. Although
      under the cautious perspective required by the possible context-dependency of the
      present findings, this study contributes to the cost-benefit analysis
      (environmental risk versus the achievement of the intended objectives) of CCS
      strategies.

PMID- 29571405
TI  - Improving the implementation of marine monitoring in the northeast Atlantic.
AB  - Marine monitoring in the northeast Atlantic is delivered within identifiable
      monitoring themes, established through time and defined by the geographical area
      and policy drivers they serve, the sampling methodologies they use, their
      assessment methodologies, their funding and governance structures and the people
      or organisations involved in their implementation. Within a monitoring theme,
      essential components for effective monitoring are governance, strategy and work
      plan, sampling protocols, quality assurance, and data and assessment structures.
      This simple framework is used to analyse two monitoring theme case studies;
      national ecosystem health monitoring, and regional fish stock monitoring. Such
      essential component analyses, within marine monitoring themes, can help improve
      monitoring implementation by identifying gaps and overlaps. Once monitoring
      themes are recognised, explicitly defined and streamlined, travel towards
      integrated monitoring may be made easier as the current lack of clarity in
      thematic marine monitoring implementation is one barrier to integration at both
      national and regional scales.

PMID- 29571406
TI  - Securing a port's future through Circular Economy: Experiences from the Port of
      Gavle in contributing to sustainability.
AB  - Ports are an important player in the world, due to their role in global
      production and distributions systems. They are major intermodal transport hubs,
      linking the sea to the land. For all ports, a key requirement for commercial and
      economic viability is to retain ships using them and to remain accessible to
      those ships. Ports need to find approaches to help them remain open. They must
      ensure their continued economic viability. At the same time, they face increasing
      pressure to become more environmentally and socially conscious. This paper
      examines the approach taken by the Port of Gavle, Sweden, which used contaminated
      dredged materials to create new land using principles of Circular Economy. The
      paper demonstrates that using Circular Economy principles can be a viable way of
      securing a port's future and contributing to its sustainability, and that of the
      city/region where it operates.

PMID- 29571407
TI  - Source identification and risk assessment based on fractionation of heavy metals
      in surface sediments of Jiaozhou Bay, China.
AB  - To identify sources and evaluate ecological risks of heavy metals in sediments of
      Jiaozhou Bay, contents and chemical fractions of Cd, Cr, Cu, Pb, Zn, Ni, Sb and
      Sn were studied. Results suggested that higher metal contents appeared at inner
      bay and near marine dumping area. Labile fractions of heavy metals accounted for
      0.5-77% (~36%) of total contents indicating their significant anthropogenic
      sources. The enrichment levels of Cd and Sb were relatively higher. Cu, Ni, Cd
      and Zn were at low to medium risks. Cr, Pb, Sn and Sb were at no or low risks.
      Total contents of heavy metals were mainly controlled by natural sources, while
      anthropogenic inputs were important sources of labile fractions of heavy metals
      in sediments of Jiaozhou Bay with industrial and domestic activities as main
      contributors for Cu, Pb, Zn, Cr, Ni and Sn, and agricultural activities for Cd
      and regional coal combustion for Sb.

PMID- 29571408
TI  - Widespread sewage pollution of the Indian River Lagoon system, Florida (USA)
      resolved by spatial analyses of macroalgal biogeochemistry.
AB  - The Indian River Lagoon (IRL) system, a poorly flushed 240 km long estuary in
      east-central Florida (USA), previously received 200 MLD of point source municipal
      wastewater that was largely mitigated by the mid-1990's. Since then, non-point
      source loads, including septic tank effluent, have become more important. Seventy
      sites were sampled for bloom-forming macroalgae and analyzed for delta15N, %
      nitrogen, % phosphorus, carbon:nitrogen, carbon:phosphorus, and
      nitrogen:phosphorus ratios. Data were fitted to geospatial models showing
      elevated delta15N values (>+50/00), matching human wastewater in most of the IRL
      system, with elevated enrichment (delta15N >= +70/00 to +100/00) in urbanized
      portions of the central IRL and Banana River Lagoon. Results suggest increased
      mobilization of OSDS NH4+ during the wetter 2014 season. Resource managers must
      improve municipal wastewater treatment infrastructure and commence significant
      septic-to-sewer conversion to mitigate nitrogen over-enrichment, water quality
      decline and habitat loss as mandated in the Tampa and Sarasota Bays and the
      Florida Keys.

PMID- 29571409
TI  - Occurrence of microplastics in commercial fish from a natural estuarine
      environment.
AB  - Microplastic ingestion has been reported for several marine species, but the
      level of contamination in transitional systems and associated biota is less
      known. The aim of this study was to assess the occurrence of microplastic
      ingestion in three commercial fish species: the sea bass (Dicentrarchus labrax),
      the seabream (Diplodus vulgaris) and the flounder (Platichthys flesus) from the
      Mondego estuary (Portugal). Microplastics were extracted from the
      gastrointestinal tract of 120 individuals by visual inspection and digestion
      solution. A total of 157 particles were extracted from 38% of total fish (96%
      fibers), with 1.67 +/- 0.27 (SD) microplastics per fish. Significantly higher
      amount of ingested microplastics was recorded for D. vulgaris (73%). The dominant
      polymers identified by MU-FTIR were polyester, polypropylene and rayon (semi
      synthetic fiber). It is reported for the first time the presence of this
      pollutant in fish populations from the Mondego estuary raising concerns on their
      potential negative effects.

PMID- 29571410
TI  - Pollutant bioaccumulation in the California spiny lobster (Panulirus interruptus)
      in San Diego Bay, California, and potential human health implications.
AB  - While the California spiny lobster (Panulirus interruptus) is an important
      commercial and recreational fishery species in California, there is a lack of
      data on bioaccumulation for the species. This study examined pollutant tissue
      concentrations in lobsters from San Diego Bay, California. Observed lobster
      pollutant tissue concentrations in tail muscle were compared to State of
      California pollutant advisory levels. Concentrations were then used to conduct
      risk assessment using catch data from the California Department of Fish and
      Wildlife. Study results found little bioaccumulation of organic pollutants in
      tail tissue, likely due to low observed lipids. Mercury was present,
      predominantly in methyl form, at concentrations above advisory levels.
      Recreational catch data for San Diego Bay showed increased non-cancer risk for
      fishers at the 90th percentile or greater of reported annual catch. Further
      studies should focus on non-tail tissues, as exploratory whole lobster samples (n
      = 2) showed elevated organic pollutants and metals.

PMID- 29571411
TI  - Phylogenetic characterization of culturable bacteria and fungi associated with
      tarballs from Betul beach, Goa, India.
AB  - Tarballs are semisolid blobs of crude oil, normally formed due to weathering of
      crude-oil in the sea after any kind of oil spills. Microorganisms are believed to
      thrive on hydrocarbon-rich tarballs and possibly assist in biodegradation. The
      taxonomy of ecologically and economically important tarball-associated microbes,
      however, needs improvement as DNA-based identification and phylogenetic
      characterization have been scarcely incorporated into it. In this study, bacteria
      and fungi associated with tarballs from touristic Betul beach in Goa, India were
      isolated, followed by phylogenetic analyses of 16S rRNA gene and the ITS sequence
      data to decipher their clustering patterns with closely-related taxa. The gene
      sequence analyses identified phylogenetically diverse 20 bacterial genera
      belonging to the phyla Proteobacteria (14), Actinobacteria (3), Firmicutes (2)
      and Bacteroidetes (1), and 8 fungal genera belonging to the classes
      Eurotiomycetes (6), Sordariomycetes (1) and Leotiomycetes (1) associated with the
      Betul tarball samples. Future studies employing a polyphasic approach, including
      multigene sequence-data, are needed for species-level identification of
      culturable tarball-associated microbes. This paper also discusses potentials of
      tarball-associated microbes to degrade hydrocarbons.

PMID- 29571412
TI  - Microplastic analysis in the South Funen Archipelago, Baltic Sea, implementing
      manta trawling and bulk sampling.
AB  - Microplastic contamination in surface waters of the South Funen Archipelago in
      Denmark was assessed. Therefore, ten manta trawls were conducted in June 2015.
      Moreover, 31 low-volume bulk samples were taken to evaluate, whether consistent
      results in comparison to the net-based approach can be obtained. Microplastic
      contamination in the South Funen Archipelago (0.07 +/- 0.02 particles/m3) is
      slightly below values reported before. The sheltered position of the study area,
      low population pressure on adjacent islands and the absence of any major
      potential point sources were identified as major factors explaining the low
      concentration of microplastics. Within the Archipelago, harbors or marinas and
      the associated vessel traffic are the most probable sources of microplastics. The
      concentration of microplastics in low-volume bulk samples is not comparable to
      manta trawl results. This is mainly due to insufficient representativeness of the
      bulk sample volumes.

PMID- 29571413
TI  - Foraminiferal single chamber analyses of heavy metals as a tool for monitoring
      permanent and short term anthropogenic footprints.
AB  - In order to establish environmentally sustainable industries there is a need for
      high-resolution temporal and spatial monitoring of heavy metal pollutants even at
      low concentrations before they become hazardous for local ecosystems. Here we
      present single chamber records of Cu, Zn and Pb in shells of two benthic
      foraminifera species with different shell types from two shallow coastal stations
      in Israel: An area adjacent to an electrical power plant and desalination factory
      (Hadera) and an industrially free nature reserve (Nachsholim). Records of both
      foraminifera species show elevated metal concentrations in Hadera clearly
      identifying the footprint of the local industrial facilities. Moreover, short
      term events of elevated Cu and Pb concentrations were detected by single chamber
      analyses. This study demonstrates the potential of using heavy metals anomalies
      in foraminiferal single chambers as a tool for detecting the industrial footprint
      of coastal facilities as well as short term events of elevated heavy metals.

PMID- 29571414
TI  - The relationship between metal concentrations in seagrass (Zostera capricorni)
      tissue and ambient fine sediment in modified and near-pristine estuaries (Sydney
      estuaries, Australia).
AB  - Seagrass (Zostera capricorni) tissue metal concentrations in Sydney estuary are
      some of the highest reported for urban environments. A strong declining metal
      (As, Co, Cr, Cu, Mn, Pb and Zn) concentration gradient in fine sediment from
      highly modified to the near-pristine estuarine environments was matched by a
      concurrent and statistically significant, moderately strong, relationship with
      declining metal concentrations for leaf, rhizomes and root tissue types. Leaf
      tissue more consistently expressed metal concentration uptake from sediment.
      Rhizome tissue contained the highest concentrations for all metals, except Mn,
      while leaf concentrations were higher for Cr and Zn and roots were more elevated
      in Cr and Pb. Tissue Cr, Pb and Zn were close to background for reference sites
      for leaves. Maximum tissue enrichment over background was 25, 19, 47 and 8 times
      for Cr, Cu, Pb and Zn. Bio-sediment accumulation factors were generally <1 for
      all metals.

PMID- 29571415
TI  - Distribution and metal contamination in the coastal sediments of Dammam Al-Jubail
      area, Arabian Gulf, Saudi Arabia.
AB  - Present work aims to document the distribution and metal contamination in the
      coastal sediments of the Dammam Al-Jubail area, Saudi Arabian Gulf. Twenty-six
      samples were collected for Al, V, Cr, Mn, Cu, Zn, Cd, Pb, Hg, Sr, As, Fe, Co and
      Ni analysis. Results of enrichment factor indicated that Sr, Cd, Cu, Hg, V, As,
      Ni, Cr and Zn gave enrichment factors higher than 2 (98.87, 40.28, 33.20, 27.87,
      26.11, 14.10, 6.15, 3.72 and 2.62 respectively) implying anthropogenic sources,
      while Pb, Mn and Al have very low background level (1.37, 0.71, 0.124
      respectively), probably originated from natural sources. Average concentrations
      of Sr, V, Hg, Cd and As were mostly higher than those from the background shale
      and the earth crust, the Caspian Sea, the Mediterranean Sea, the sediment quality
      guidelines, the Red Sea, the Gulf of Aqaba and the Gulf of Oman. The higher
      levels of the studied metals are mostly related samples with high Al and TOM
      content, as well as the visible anthropogenic pollutants along the studied
      coastline. The most recorded anthropogenic pollutants were sewage effluent,
      landfilling due to coastal infrastructure development, oil spills, petrochemical
      industries and desalination plants in Al-Jubail industrial city.

PMID- 29571416
TI  - The underwater acoustic environment at SGaan Kinghlas-Bowie Seamount Marine
      Protected Area: Characterizing vessel traffic and associated noise using
      satellite AIS and acoustic datasets.
AB  - Vessel traffic is one of the most wide-spread anthropogenic contributors to ocean
      noise worldwide and has the potential to alter ecosystems upon which cetaceans
      and other acoustically sensitive marine organisms rely. Canada's SGaan Kinghlas
      Bowie Seamount Marine Protected Area (SK-B MPA) is one such area whose productive
      ecosystem could benefit from greater monitoring of human induced threats in order
      to inform management. Despite earning official designation as a Marine Protected
      Area under the Oceans Act in 2008, little remains known about vessel traffic in
      the region and the associated potential impacts on vulnerable marine species.
      Therefore, to increase our understanding of vessel traffic and accompanying noise
      at SK-B MPA, satellite AIS and acoustic data were investigated. The results of
      this study suggest that variations in ambient sound levels in the region are
      driven by near and distant shipping events, thus having implications for future
      management of the MPA.

PMID- 29571417
TI  - Ingestion of microplastics and natural fibres in Sardina pilchardus (Walbaum,
      1792) and Engraulis encrasicolus (Linnaeus, 1758) along the Spanish Mediterranean
      coast.
AB  - The ingestion of microplastics and natural fibres (<5 mm) was assessed for two
      commercial fish species in the western Mediterranean Sea: Sardina pilchardus and
      Engraulis encrasicolus. Gastrointestinal tracts from 210 individuals from 14
      stations were examined with 14.28-15.24% of the small pelagic fish S. pilchardus
      and E. encrasicolus having ingested microplastics and natural fibres. A
      latitudinal increase in condition index (Fulton's K) of S. pilchardus gave an
      indication that larger individuals with better physical condition are less likely
      to ingest microplastics and natural fibres. Fibres were the most frequent
      particle type (83%) and Fourier Transform Infrared spectroscopy (FT-IR) analysis
      indicated polyethylene terephthalate was the most common microplastics material
      (30%). Results from this study show that both microplastics and natural fibres of
      anthropogenic origin are common throughout the pelagic environment along the
      Spanish Mediterranean coast.

PMID- 29571419
TI  - Women and Peripheral Arterial Disease: A Review of Sex Differences in
      Epidemiology, Clinical Manifestations, and Outcomes.
AB  - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in
      women. Peripheral arterial disease (PAD), a manifestation of CVD and a marker for
      other adverse CVD outcomes such as ischemic heart disease and stroke, remains
      underrecognized and undertreated in women. Contrary to the previous belief that
      PAD is mainly a disease of white men, contemporary data suggest equal, if not
      higher, prevalence rates in nonwhite women. Women often present with asymptomatic
      or atypical disease and seek medical attention with more advanced disease.
      Cardiovascular morbidity and mortality rates, as well as procedural mortality
      rates, remain elevated in women compared with men. There are sex-specific markers
      and comorbidities with a higher female prevalence that are associated with PAD.
      Greater focus on PAD in cardiovascular trials, equivalent enrollment of women in
      large trials, and focused prevention strategies may help reduce the economic
      burden and adverse outcomes associated with PAD in women.

PMID- 29571418
TI  - Mapping elemental contamination on Palmyra Atoll National Wildlife Refuge.
AB  - Palmyra Atoll, once a WWII U.S. Navy air station, is now a U.S. National Wildlife
      Refuge with nearly 50km2 of coral reef and 275ha of emergent lands with forests
      of Pisonia grandis trees and colonies of several bird species. Due to the known
      elemental and organic contamination from chemicals associated with aviation,
      power generation and transmission, waste management, and other air station
      activities, a screening survey to map elemental concentrations was conducted. A
      map of 1944 Navy facilities was georeferenced and identifiable features were
      digitized. These data informed a targeted survey of 25 elements in soils and
      sediment at locations known or suspected to be contaminated, using a hand-held X
      ray fluorescence spectrometer. At dozens of locations, concentrations of elements
      exceeded established soil and marine sediment thresholds for adverse ecological
      effects. Results were compiled into a publically available geospatial dataset to
      inform potential remediation and habitat restoration activities.

PMID- 29571420
TI  - Sex Considerations in Aneurysm Formation, Progression, and Outcomes.
AB  - Aneurysm formation is a complex multifactorial process with both genetic and
      environmental influences. Over recent years, there has been increasing
      recognition of sex-specific differences regarding the prevalence and natural
      history of cardiovascular diseases in the population. In particular, there is a
      growing body of evidence showing that aneurysm behaviour differs based on sex.
      Although most types of aneurysms are more common in men, their growth rates and
      outcomes are worse in women. This fact raises attention about potential
      underlying differences in the arteries of men and women that may contribute to
      differences in aneurysm prevalence and outcomes. There are complex biochemical
      and mechanical mechanisms at play that contribute to vascular health.
      Furthermore, many studies have suggested potential differences in the hormonal
      milieu and underlying arterial anatomy between men and women. Based on the data
      reviewed in this article, assessment of the underlying pathophysiology of
      aneurysms in women might prove clinically useful regarding prevention, early
      detection, and management of aneurysms in women. Sex-specific research,
      screening, and treatment guidelines for aneurysm disease should be introduced to
      reflect the differing natural history of these diseases in men and women.

PMID- 29571421
TI  - Mechanisms and Clinical Significance of Endothelial Dysfunction in High-Risk
      Pregnancies.
AB  - The maternal cardiovascular system undergoes critical anatomic and functional
      adaptations to achieve a successful pregnancy outcome which, if disrupted, can
      result in complications that significantly affect maternal and fetal health.
      Complications that involve the maternal cardiovascular system are among the most
      common disorders of pregnancy, including gestational hypertension, preeclampsia,
      gestational diabetes, and impaired fetal growth. As a central feature, maternal
      endothelial dysfunction is hypothesized to play a predominant role in mediating
      the pathogenesis of these high-risk pregnancies, and as such, might proceed and
      precipitate the clinical presentation of these pregnancy disorders. Improving or
      normalizing maternal endothelial function in high-risk pregnancies might be an
      effective therapeutic strategy to ameliorate maternal and fetal clinical
      outcomes.

PMID- 29571422
TI  - Atherosclerotic Heart Disease in Women With Autoimmune Rheumatologic Inflammatory
      Conditions.
AB  - Women have a higher prevalence of several inflammatory rheumatologic conditions.
      These include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and
      systemic sclerosis (SSc) to name a few. These conditions are all associated with
      higher rates of cardiovascular (CV) morbidity and mortality, which is driven
      primarily by atherosclerotic heart disease. Traditional risk factors are
      important considerations in the assessment of CV risk in the rheumatologic
      patient; however, these factors do not appear to impart a similar weight of risk
      in women with inflammatory autoimmune rheumatologic conditions. In addition, even
      when controlling for traditional risk factors, patients with RA or SLE continue
      to have a higher risk of CV events, which has been linked to the burden of
      systemic inflammation. Currently, the CV risk scoring systems available for the
      general population underestimate the burden of the problem in these complex
      patients. The increased CV risk in patients with rheumatologic diseases has been
      reported in the literature for years but remains underrecognized by internists
      and cardiologists. Although these conditions themselves are relatively rare, the
      further study of inflammation and its treatment in CV disease will be beneficial
      to the general population.

PMID- 29571423
TI  - Recent Developments in Sex-Related Differences in Presentation, Prognosis, and
      Management of Coronary Artery Disease.
AB  - Coronary artery disease (CAD) is the most prevalent type of heart disease among
      women and men. Sex-related differences in the presentation, prognosis, and
      management of patients with CAD has been increasingly studied. Compared with men,
      women are more likely to present with multiple comorbidities, have a higher
      prevalence of psychological risk factors, and present with atypical symptoms.
      These factors, along with delays in seeking medical attention, might contribute
      to sex-related treatment differences in women with stable angina and acute
      coronary syndrome. This review article highlights recent evidence examining sex
      related differences in stable CAD patients with obstructive CAD, nonobstructive
      CAD, as well as myocardial infarction.

PMID- 29571424
TI  - Optimizing Risk Stratification and Noninvasive Diagnosis of Ischemic Heart
      Disease in Women.
AB  - Ischemic heart disease (IHD) is an important and previously underappreciated
      cause of significant morbidity and mortality in women. Key differences exist in
      the pathophysiology, sex-specific risk factors, and clinical presentation in
      women compared with men, which influence diagnostic accuracy and utility of
      pretest risk assessments and noninvasive testing. Women are disproportionately
      affected by ischemia from microvascular dysfunction as evidenced by having less
      obstructive coronary artery disease on angiography, contributing to the challenge
      in diagnosis and prognosis of IHD in women via conventional methods, which tend
      to emphasize detection of epicardial stenoses. In this article, we review the
      utility, evidence for, and challenges of currently available risk assessments and
      noninvasive cardiac diagnostic tests in women. We propose an approach to
      investigation of the symptomatic woman with suspected IHD and selection of the
      appropriate testing modality. Finally, we explore opportunities for future
      research and highlight the urgent need for updated, evidence-based, Canadian
      guidelines specific to women with IHD.

PMID- 29571425
TI  - Coronary Surgery in Women and the Challenges We Face.
AB  - This review was undertaken to understand the dynamics that have shaped our
      current treatment of women who undergo coronary artery bypass grafting (CABG) and
      summarize the current literature on surgical revascularization in women. There
      has been improved access to CABG over the past several decades. Despite this,
      compared with men, CABG in women involves fewer grafts and less frequent use of
      arterial grafts, the latter having improved long-term patency compared with
      saphenous vein grafts. We attempt to determine whether the adverse clinical
      profile of women, when referred for CABG is responsible for this finding. Female
      coronary anatomy and pathophysiology are reviewed and an attempt is made to
      understand how this might affect decisions of selection and outcome measures post
      CABG. We review the short-term, long-term, and quality of life outcomes in women.
      These data are taken from large databases, as well as from more recent
      publications. Randomized controlled trial data and meta-analytic data are used
      when available. Differential use of and outcomes of surgical strategies,
      including off-pump CABG and total arterial revascularization, are contrasted with
      those in men. This review shows that there continues to be widespread differences
      in surgical approach to coronary artery disease in female vs male patients. We
      provide evidence suggestive of the existence of issues specific to women that
      affect selection for surgical procedures and outcomes in women. More work is
      required to understand the reason for these differences and how to optimize sex
      specific outcomes.

PMID- 29571426
TI  - Cardiovascular Disease Among Women From Vulnerable Populations: A Review.
AB  - On a global scale, cardiovascular disease (CVD) is the leading cause of
      mortality. It is also the number 1 cause of death among women, resulting in 8.6
      million deaths annually and constituting one third of all deaths in women
      worldwide. The burden of CVD and related risk factors has taken priority in the
      policy development for noncommunicable diseases. However, vulnerable populations,
      defined here as women who are socially or economically disadvantaged (eg, low
      income), nonwhite (specifically South Asian and indigenous women), and those who
      are elderly have often been overlooked in these discussions. These additional
      vulnerabilities, which may exist independently or in combination, place such
      women at higher risk for CVD. Specifically, these vulnerabilities include low
      socioeconomic status, a low sense of control, high stress, South Asian or
      indigenous ancestry, and increased age. Thus it is vital that we initiate a
      multipronged approach to CVD prevention that includes rigorous monitoring of CVD
      risk factors in high-risk populations and the implementation of timely, accurate,
      and contextually tailored prevention programs, services, and treatments. Well
      trained nonphysician health care workers can support the accurate monitoring and
      management of CVD and CVD risk factors so that groups of women who may otherwise
      be overlooked can receive adequate attention.

PMID- 29571427
TI  - Myocardial Infarction With No Obstructive Coronary Artery Disease: Angiographic
      and Clinical Insights in Patients With Premature Presentation.
AB  - BACKGROUND: Premature myocardial infarction (MI) is an increasingly prevalent
      cause of morbidity and mortality worldwide. A subset of patients, predominantly
      young women, present with MI with no obstructive coronary artery disease
      (MINOCA), a nomenclature gaining recognition. However, few data exist on
      presentation and prognosis according to the severity of coronary artery disease
      (CAD). METHODS: We studied patients with premature (younger than 55 years of age)
      acute MI enrolled in a large cohort in 24 centres across Canada. Baseline
      clinical, psychosocial, and coronary anatomy characteristics as well as 12-month
      outcomes were compared between patients with MINOCA (< 50% stenosis) and patients
      with MI with obstructive CAD (>= 50% stenosis; MICAD). RESULTS: From a cohort of
      1210 patients with acute coronary syndrome, we examined 998 MI patients with
      available angiography core lab readings: 82 (8.2%) had a MINOCA and 916 (91.8%)
      had a MICAD. Forty percent of patients with MINOCA were women compared with one
      third with MICAD. The prevalence of traditional risk factors and chest pain at
      presentation was lower in MINOCA patients, yet 37% had a ST-elevation MI and 10%
      presented with a cardiac arrest. No evident etiology was detected in > 70% of
      MINOCA, but 10% presented with either spontaneous coronary dissection or
      Takotsubo cardiomyopathy. Although combined major adverse cardiovascular events
      and all-cause readmission rate was lower in the MINOCA group (14% vs 25%;
      adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93), it was not
      negligible. CONCLUSIONS: Patients with MINOCA present with high-risk features
      despite the absence of obstructive CAD. A search for etiology and eventual
      treatment provides a rich avenue for improving prognosis in young women with
      premature MI.

PMID- 29571428
TI  - Sex Differences in Left Ventricular Cavity Dilation and Outcomes in Acute Heart
      Failure Patients With Left Ventricular Systolic Dysfunction.
AB  - BACKGROUND: In this study we evaluated the influence of sex on the left
      ventricular end-diastolic dimension (LVEDD) and adverse outcomes in patients
      hospitalized for acute decompensated heart failure (HF) with a reduced ejection
      fraction (EF). METHODS: Among the 4842 patients enrolled in the Acute
      Decompensated Heart Failure Syndromes (ATTEND) registry, 2367 patients (1607 men
      and 760 women) discharged alive after hospitalization for acute decompensated HF
      with a reduced EF (defined as a left ventricular EF < 50%) were investigated to
      assess the association of sex and LVEDD with the primary end point (all-cause
      death and readmission for HF after discharge). Men and women were separately
      divided into LVEDD quartiles at discharge (men: LVEDD <= 54, 55-60, 61-65, and >=
      66 mm; women: LVEDD <= 48, 49-54, 55-60, and >= 61 mm). The median follow-up
      period after discharge was 524 (range, 385-785) days. RESULTS: Occurrence of the
      primary end point did not differ between men and women (37.0% vs 37.2%; P =
      0.921). After adjustment for multiple comorbidities including left ventricular
      EF, men with an LVEDD of 61-65 and >= 66 mm had a significantly higher risk of
      the primary end point than men with an LVEDD <= 54 mm, indicating a positive
      association between a larger LVEDD and adverse outcomes. In contrast, in women,
      the adjusted risk of the primary end point was comparable among the LVEDD
      quartiles. CONCLUSIONS: Men and women with acute decompensated HF and a reduced
      EF might show important differences in relation to the association between left
      ventricular cavity dilation and outcomes.

PMID- 29571429
TI  - Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation
      During Late Pregnancy.
AB  - BACKGROUND: Cardiovagal baroreflex gain (cBRG) reflects an individual's ability
      to buffer swings in blood pressure. It is not well understood how this mechanism
      is influenced by physical activity in pregnancy. Because pregnant women tend to
      engage in low levels of moderate-to-vigorous physical activity (MVPA) and high
      levels of sedentary behaviour, we sought to determine the influence of MVPA and
      sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.
      METHODS: Fifty-eight third trimester (31.9 +/- 3.0 weeks) normotensive pregnant
      women (31.2 +/- 2.8 years) were tested. Heart rate (electrocardiogram) and blood
      pressure (systolic blood pressure and MAP; finger photoplethysmography) were
      collected on a beat-by-beat basis, and averaged over 3 minutes of rest.
      Spontaneous cBRG was calculated as the slope of the relationship between
      fluctuations in systolic blood pressure and heart rate. Objective measures of
      MVPA and sedentary behaviour were collected over a 7-day period using an
      ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL). RESULTS:
      Participants spent 67.5 +/- 7.9% of waking hours engaged in sedentary behaviour,
      and performed 68.6 +/- 91.9 minutes of MVPA per week. Sedentary behaviour was not
      related to cBRG (r = -0.035; P = 0.793) or MAP (r = -0.033; P = 0.803). However,
      MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r =
      -0.115; P = 0.389). The association between MVPA and cBRG remained significant
      after controlling for age, pre-pregnancy body mass index, gestational age, and
      wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater
      amounts of MVPA showed increased cBRG. CONCLUSIONS: Our data suggest that
      increased MVPA, but not necessarily reduced sedentary behaviour, might be
      beneficial for reflex control of blood pressure during pregnancy.

PMID- 29571430
TI  - No-HDL-cholesterol as risk marker and therapeutic goal.

PMID- 29571431
TI  - The analysis of translational mechanisms that modulate gene expression.

PMID- 29571432
TI  - Young Males and Reproductive Health Care: Are We There?

PMID- 29571433
TI  - Collaboration Is Key to Developing Effective Hormonal Treatment Paradigms for
      Transgender Youth.

PMID- 29571434
TI  - Adolescent Oral Sex and Condom Use: How Much Should We Worry and What Can We Do?

PMID- 29571435
TI  - Megalin/cubilin has a minor role in the proximal tubular cell uptake of filtered
      albumin.

PMID- 29571436
TI  - The Authors Reply.

PMID- 29571437
TI  - Taurolidine-based lock solutions for hemodialysis catheters: the enthusiasm
      should be tempered.

PMID- 29571438
TI  - Immunological remission in PLA2R-antibody-associated membranous nephropathy:
      cyclophosphamide versus rituximab.

PMID- 29571439
TI  - The Authors Reply.

PMID- 29571440
TI  - Fu J, Wang Z, Lee K, et al. Transcriptomic analysis uncovers novel synergistic
      mechanisms in combination therapy for lupus nephritis. Kidney Int. 2018;93:416
      429.

PMID- 29571441
TI  - Liu J, Dong Z. Neutrophil extracellular traps in ischemic AKI: new way to kill.
      Kidney Int. 2018;93:303-305.

PMID- 29571442
TI  - Wyatt CM, Le Meur Y. REPRISE: tolvaptan in advanced polycystic kidney disease.
      Kidney Int. 2018;93:292-295.

PMID- 29571443
TI  - Osteopetrosis with renal tubular acidosis and cerebral calcification.

PMID- 29571444
TI  - Uremic cranial neuropathy.

PMID- 29571445
TI  - The Case | Shining a light on an unusual case of chronic kidney disease.

PMID- 29571447
TI  - IL-17A-induced mesenchymal stem cells have promising therapeutic value for
      clinical translation.
AB  - Interferon (IFN) gamma is the prototypic proinflammatory cytokine used to
      preactivate the immunomodulatory properties of mesenchymal stem cells (MSC). IFN
      gamma, however, converts MSC into a cell therapy that can be immunogenic,
      detrimental, and hence nonfeasible for clinical application. The article by Bai
      et al. is an in vivo proof-of-concept study that interleukin-17A (IL-17A)
      enhances the immunosuppressive, tolerance-promoting, and renoprotective
      properties of MSC. IL-17A is an alternative cytokine to preactivate MSC. IL-17A
      enhances the therapeutic efficacy of MSC for renal diseases.

PMID- 29571448
TI  - Atypical chemokine receptors-"chemokine PACMANs" as new therapeutic targets in
      glomerulonephritis.
AB  - Inflammatory cells are recruited to sites of inflammation by chemokines. Atypical
      chemokine receptors regulate chemokine gradients, thereby limiting inflammation.
      In this issue of Kidney International, atypical chemokine receptor 2 knockouts
      were described to be increasingly susceptible to immune complex-mediated
      glomerulonephritis. By degrading CCL2, atypical chemokine receptor 2 limited the
      recruitment of immune cells and myofibroblasts to the renal interstitial
      compartment. Therefore, not only inflammation, but also fibrosis, was effectively
      inhibited, making atypical chemokine receptor 2 an attractive therapeutic target
      in glomerulonephritis.

PMID- 29571449
TI  - U-shaped dietary sodium-associated incidence of chronic kidney disease cautions
      against salt overrestriction in hypertension.
AB  - In this population study salt intake is not associated with development of
      chronic kidney disease (CKD) in individuals with normal blood pressure, whereas
      in hypertensive individuals both low and high salt intakes are associated with
      increased incidence of CKD, similar to U-shaped associations between salt intake
      and mortality found in previous studies. The results contribute to the
      skepticism, which has questioned the present public health policy to reduce salt
      intake below 5.8 g.

PMID- 29571450
TI  - Update on renal blood oxygenation level-dependent MRI to assess intrarenal
      oxygenation in chronic kidney disease.
AB  - Identifying subjects with progressive chronic kidney disease will be important
      both in clinical practice and in conducting clinical trials. Pruijm et al. (in
      this issue) demonstrate for the first time that cortical oxygenation as evaluated
      by blood oxygenation level-dependent magnetic resonance imaging can predict
      future loss of renal function. These observations provide the necessary stimulus
      to continue the development of renal blood oxygenation level-dependent magnetic
      resonance imaging to further improve the sensitivity and specificity to renal
      oxygenation and hence the predictive power.

PMID- 29571451
TI  - Arrhythmia in hemodialysis patients and its relation to sudden death.
AB  - Sudden death in patients on hemodialysis is believed to be due to arrhythmia, but
      the evidence for this is surprisingly limited. Five studies involving implantable
      loop recorders in patients on hemodialysis have now been published, and 4 have
      shown that bradyarrhythmia rather than tachyarrhythmia are the pre-eminent
      arrhythmic associations of fatal events. The Monitoring in Dialysis study,
      reported in this issue, sheds new light on the relationships of arrhythmia to the
      conventional 3-session weekly hemodialysis cycle.

PMID- 29571452
TI  - Lipids, inflammation, and chronic kidney disease: a SHARP perspective.
AB  - Accumulating evidence indicates that inflammation plays a role in the initiation
      and progression of chronic kidney disease. In the Study of Heart and Renal
      Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline
      low-density lipoprotein cholesterol levels were both associated with a higher
      risk of cardiovascular events, but higher baseline C-reactive protein levels were
      also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe
      reduced cardiovascular events independent of baseline C-reactive protein levels.
      However, this observation does not exclude inflammation as a causal factor for
      cardiovascular disease development in chronic kidney disease patients.

PMID- 29571453
TI  - Increasing inclusion of patients with advanced chronic kidney disease in
      cardiovascular clinical trials.

PMID- 29571454
TI  - Hexanal as a QS inhibitor of extracellular enzyme activity of Erwinia carotovora
      and Pseudomonas fluorescens and its application in vegetables.
AB  - To prevent the postharvest disease of Chinese cabbage and lettuce, hexanal was
      used as a control measure to inhibit N-acyl homoserine lactone (AHL) production
      and extracellular enzymes regulated by quorum-sensing (QS) in their main spoilage
      strains of Erwinia carotovora and Pseudomonas fluorescens. Firstly, the QS
      inhibition of hexanal was verified by significantly inhibiting violacein
      production (p < 0.05) in Chromobacterium violaceum CV026 at sub-MICs. beta
      Galactosidase activities which reflected AHL production, were significantly
      inhibited by hexanal, its inhibitory effect was concentration-dependent under
      minimal inhibitory concentration (MIC) (p < 0.05). The detected extracellular
      enzymes activities decreased with the increase of hexanal concentration (p <
      0.05), including cellulase, xylanase, pectate lyase, polygalacturonase, and
      protease. Chinese cabbage soft rot and lettuce leaf scorch could be significantly
      inhibited by hexanal (p < 0.05) without any phytotoxicity effect, the 1/2 MIC of
      hexanal showed the best inhibitory effect. And all the above effects showed a
      dose-dependent. A novel preservation technique in reducing the loss of vegetables
      due to spoilage based on the QS inhibitor was developed.

PMID- 29571455
TI  - Non-enzymatic electrochemical platform for parathion pesticide sensing based on
      nanometer-sized nickel oxide modified screen-printed electrodes.
AB  - Nanozyme-based electrochemical sensors have attracted much attention because of
      their low cost, sensitivity and remarkable stability under extensive
      environmental and industrial conditions. Interestingly, the physical
      characteristics of the nanomaterials in terms of size, shape, composition,
      surface area and porosity dominate the electrochemical processes at electrode
      surfaces. Herein, we explore nickel oxide nanoplatelets (NPs) modified screen
      printed electrode-based nanozyme sensors that displays high electrochemical
      activity including stability, sensitivity, selectivity and applicability for
      organophosphate pesticide (Parathion) determination. Differential pulse
      voltammogram of NiO-SPE in presence of parathion showed a characteristic peak
      current at -1.0 V (vs. Ag/AgCl). The NiO-SPE platform allows determination of
      parathion over the concentration range of 0.1-30 uM with a limit of detection
      (LOD) of 0.024 uM. The sensing platform is found to detect parathion of
      interferences without compromising the sensitivity of the sensor. Such
      interesting features offer a sensitive determination of parathion in water, urine
      and vegetable samples.

PMID- 29571456
TI  - A rapid real-time PCR method to differentiate between mottled skate (Beringraja
      pulchra) and other skate and ray species.
AB  - Skates and rays are commercially important fish in South Korea, and among them,
      Beringraja pulchra has the highest economic value. However, the similar
      morphological traits among skates and rays are often exploited for seafood fraud.
      Here, we designed both Beringraja pulchra-specific and skate-universal primer
      sets, capable of detecting short sequences in the cytochrome oxidase subunit I
      gene, and developed highly sensitive and reliable quantitative real-time PCR
      (qPCR) assays to differentiate between Beringraja pulchra and other skate and ray
      species. ADeltaCq method based on differences in the amplification efficiency was
      developed, validated, and then used to confirm the presence of Beringraja pulchra
      in twenty-six commercial skate products. The averageDeltaCq value obtained for
      other skate species (18.94 +/- 3.46) was significantly higher than that of
      Beringraja pulchra (1.18 +/- 0.15). For on-site applications, we developed an
      ultra-fast qPCR assay, allowing for completion of the entire analytical procedure
      within 30 min.

PMID- 29571457
TI  - A multi-methodological approach in the study of Italian PDO "Cornetto di
      Pontecorvo" red sweet pepper.
AB  - A multi-methodological approach was applied to study red sweet peppers (Capsicum
      annuum L.) ecotype "Cornetto di Pontecorvo" grown in a greenhouse or in open
      field. This approach includes morphological analysis, chemical composition
      determination, and biological activity evaluation of different extracts from
      pepper fruits. Untargeted analyses, namely NMR spectroscopy and mass
      spectrometry, allowed the comprehensive pepper metabolite profile of pepper pulp,
      peel and seeds hydroalcoholic and organic extracts to be determined, showing the
      presence of sugars, organic acids, amino acids and other secondary metabolites.
      Targeted analyses, such as HPLC-PDA, HPLC-TLC and spectrophotometric analyses
      allowed polyphenols, tannins, flavonoids and pigments content to be determined.
      Samples quality and freshness were verified by the low content of biogenic amines
      and mycotoxins, as determined using HPLC-FLD and HPLC-MS, respectively.
      Preliminary biological results demonstrated the ability of the organic extracts
      to inhibit alpha-amylase, a key enzyme in the control of glucose metabolism.

PMID- 29571458
TI  - Quantitative assessment of specific defects in roasted ground coffee via infrared
      photoacoustic spectroscopy.
AB  - Chemical analyses and sensory evaluation are the most applied methods for quality
      control of roasted and ground coffee (RG). However, faster alternatives would be
      highly valuable. Here, we applied infrared-photoacoustic spectroscopy (FTIR-PAS)
      on RG powder. Mixtures of specific defective beans were blended with healthy
      (defect-free) Coffea arabica and Coffea canephora bases in specific ratios,
      forming different classes of blends. Principal Component Analysis allowed
      predicting the amount/fraction and nature of the defects in blends while partial
      Least Squares Discriminant Analysis revealed similarities between blends
      (=samples). A successful predictive model was obtained using six classes of
      blends. The model could classify 100% of the samples into four classes. The
      specificities were higher than 0.9. Application of FTIR-PAS on RG coffee to
      characterize and classify blends has shown to be an accurate, easy, quick and
      "green" alternative to current methods.

PMID- 29571459
TI  - Development of 87Sr/86Sr maps as targeted strategy to support wine quality.
AB  - This study summarizes the results obtained from a systematic and long-term
      project aimed at the development of tools to assess the provenance of food in the
      oenological sector. In particular, 87Sr/86Sr isotope ratios were measured on
      statistically representative set of soils, vine branches and wines sampled in the
      production district of Modena, worldwide known for the Lambrusco wines
      production. The obtained data were used to build strontium isotopic maps able to
      objectively support the Lambrusco PDO wines origin as well as other products of
      the Modena district. Finally, a strong relationship was found between the
      87Sr/86Sr isotope ratios of soils and vine branches on a large scale,
      highlighting and confirming once more the idea that plants can also represent an
      optimal sampling device to support geographical traceability.

PMID- 29571460
TI  - Analysis of functional components and radical scavenging activity of 21 algae
      species collected from the Japanese coast.
AB  - The functional chemical substances and the antioxidant activity of lipids in 21
      marine algae along the Japanese coast were investigated. Principal component
      analysis was performed to detect any correlation between the chemical substances
      and algae phylum. Chlorophyta contained a high level of beta-carotene. Rhodophyta
      contained high amounts of cholesterol, beta-sitosterol, and saturated fatty
      acids. Phaeophyta were rich in fucosterol, alpha-tocopherol, fucoxanthin, and
      polyphenol. Phaeophyta algae also showed the highest antioxidant activity
      compared with other phylum. This suggests that Phaeophyta has the greatest
      potential to be used as a functional food. Consumption of the beneficial
      Phaeophyta species, such as Eisenia arborea Areschoug and Ecklonia cava Kjellman
      should be encouraged as not only as food products but also as nutraceuticals and
      dietary supplements. These beneficial ingredients should be encouraged to be
      studied in depth with the possibility to develop specific formulated products
      target to special consumer's population with added nutritional value.

PMID- 29571461
TI  - Heavy metal contamination in soil, food crops and associated health risks for
      residents of Ropar wetland, Punjab, India and its environs.
AB  - In the present study, an assessment of heavy metal content in soil and food crops
      (wheat, rice, maize grains and mustard seeds) and associated health risks was
      carried out for residents of Ropar wetland and its environs. All the soil samples
      had high cadmium and cobalt contents, whereas, all crop samples had high contents
      of cobalt and lead. Bioconcentration factor (BCF) analysis indicated that rice
      grains act as hyper-accumulators of chromium (BCF = 17.98) and copper (BCF =
      10.91), whereas, maize grains act as hyper-accumulators of copper (BCF = 30.43).
      One-way ANOVA suggested that heavy metal content in food crops varied
      significantly at p <= 0.05 for different sites, indicating anthropogenic
      contribution of heavy metals in agricultural fields. Dietary intake of cobalt via
      all food crops posed higher non-cancer health risk to residents in comparison to
      other heavy metals. Chromium posed highest cancer risk through consumption of
      wheat grains, being staple diet in study area.

PMID- 29571462
TI  - Kinetics, biocompounds, antioxidant activity, and sensory attributes of quinces
      as affected by drying method.
AB  - Quinces are attracting interest due to their health and nutritional benefits.
      Drying kinetics, bioactive compounds, antioxidant activity, and the main sensory
      parameters were determined in dried quinces, cultivar Leskovac, as affected by
      the drying method. The highest total polyphenols content was observed in dried
      samples obtained after freeze drying and convective drying at 50  degrees C. The
      best drying treatment, considering only sensory attributes, was vacuum-microwave
      drying at 480 W, because it led to intermediate dark color and high intensities
      of basic tastes and key flavor attributes. The studied parameters were finally
      used to recommend convective drying at 60  degrees C as the most appropriate
      drying method for quinces, because it had a high content of total phenolic
      compounds (2nd best treatment out of 10), a good sensory profile, was cheap, and
      caused no negative effects on nutritional or sensory parameters; the only
      disadvantage was its long drying time.

PMID- 29571463
TI  - The taste of KCl - What a difference a sugar makes.
AB  - Dramatic increase in NaCl consumption lead to sodium intake beyond health
      guidelines. KCl substitution helps reduce sodium intake but results in a bitter
      metallic off-taste. Two disaccharides, trehalose and sucrose, were tested in
      order to untangle the chemical (increase in effective concentration of KCl due to
      sugar addition) from the sensory effects. The bitter-metallic taste of KCl was
      reduced by these sugars, while saltiness was enhanced or unaltered. The perceived
      sweetness of sugar, regardless of its type and concentration, was an important
      factor in KCl taste modulation. Though KCl was previously shown to increase the
      chemical activity of trehalose but not of sucrose, we found that it suppressed
      the perceived sweetness of both sugars. Therefore, sensory integration was the
      dominant factor in the tested KCl-sugar combinations.

PMID- 29571464
TI  - The roles of bacteria in the biochemical changes of chill-stored bighead carp
      (Aristichthys nobilis): Proteins degradation, biogenic amines accumulation,
      volatiles production, and nucleotides catabolism.
AB  - This study investigated the biochemical changes (proteins degradation, total
      volatile basic nitrogen, biogenic amines, volatile organic compounds, nucleotides
      catabolism and related enzymes) of bighead carp samples inoculated with four
      different bacteria (Shewanella putrefaciens, Aeromonas sobria, Acinetobacter
      bohemicus, and Pseudomonas helmanticensis) during storage at 4 +/- 1  degrees C.
      A. sobria exhibited the strongest proteolytic activity. A. sobria, P.
      helmanticensis, and S. putrefaciens were responsible for putrescine production,
      whereas S. putrefaciens was the sole producer of cadaverine. Alcohols and S
      compounds were mainly released by A. sobria and S. putrefaciens, respectively.
      The fastest degradation rates of hypoxanthine riboside and hypoxanthine were
      found in samples inoculated with P. helmanticensis and S. putrefaciens. Inosine
      nucleosidase was mainly resulted by A. sobria, P. helmanticensis and S.
      putrefaciens, whereas xanthine oxidase was derived from both fish muscle and
      secretions of P. helmanticensis and S. putrefaciens.

PMID- 29571465
TI  - Validation of an analytical method for the quantitative determination of selenium
      in bacterial biomass by ultraviolet-visible spectrophotometry.
AB  - The present paper describes the validation of a spectrophotometry method
      involving molecular absorption in the visible ultraviolet-visible (UV-Vis) region
      for selenium (Se) determination in the bacterial biomass produced by lactic acid
      bacteria (LAB). The method was found to be suitable for the target application
      and presented a linearity range from 0.025 to 0.250 mg/L Se. The angular and
      linear coefficients of the linear equation were 1.0678 and 0.0197 mg/L Se,
      respectively, and the linear correlation coefficient (R2) was 0.9991. Analyte
      recovery exceeded 96% with a relative standard deviation (RSD) below 3%. The Se
      contents in LAB ranged from 0.01 to 20 mg/g. The Se contents in the bacterial
      biomass determined by UV-Vis were not significantly different (p > 0.05) those
      determined by graphite furnace atomic absorption spectrometry. Thus, Se can be
      quantified in LAB biomass using this relatively simpler technique.

PMID- 29571466
TI  - Spectroscopic and docking studies on the interaction between caseins and beta
      carotene.
AB  - Natural occurrence of beta-carotene in bovine milk and the leading role of milk
      proteins in low-fat or fat-free dairy products necessitate investigating the
      possibility of interaction between beta-carotene and casein constituting up to
      80% of bovine milk proteins. In this study, molecular interaction of caseins and
      beta-carotene was analyzed using fluorescence, UV-Vis absorption, circular
      dichroism (CD), and computer-aided molecular modeling. Casein and its fractions
      were bound to beta-carotene with a binding constant of the order 104 M-1 and a
      1:1 binding stoichiometry. The binding was favored at alkaline pHs, low ionic
      strength and temperatures. kappa-Casein had the highest binding affinity to beta
      carotene, among casein fractions. The negative values of entropy and enthalpy
      changes and docking studies proved Van der Waals interactions are predominant
      forces in the binding process. The casein conformation was also altered through
      inducing a more folded structure in beta-casein and a looser conformation in
      alpha- and kappa-casein.

PMID- 29571467
TI  - The potential of kiwifruit puree as a clean label ingredient to stabilize high
      pressure pasteurized cloudy apple juice during storage.
AB  - In the fruit juice industry, high pressure (HP) processing has become a
      commercial success. However, enzymatic browning, cloud loss, and flavor changes
      during storage remain challenges. The aim of this study is to combine kiwifruit
      puree and HP pasteurization (600 MPa/3 min) to stabilize cloudy apple juice
      during storage at 4  degrees C. A wide range of targeted and untargeted quality
      characteristics was evaluated using a multivariate approach. Due to high ascorbic
      acid content and high viscosity, kiwifruit puree allowed to prevent enzymatic
      browning and phase separation of an apple-kiwifruit mixed juice. Besides, no
      clear changes in organic acids, viscosity, and particle size distribution were
      detected in mixed juice during storage. Sucrose of apple and mixed juices
      decreased with glucose and fructose increasing during storage. The volatile
      changes of both juices behaved similar, mainly esters being degraded. Sensory
      evaluation demonstrated consumer preferred the aroma of mixed juice compared to
      apple juice.

PMID- 29571468
TI  - pH-Dependency of the proteolytic formation of cocoa- and nutty-specific aroma
      precursors.
AB  - Sensory evaluation of roasted cocoa not only revealed cocoa-specific but also
      more or less pronounced nutty-specific aroma notes. Essential precursors of the
      corresponding volatile compounds could be generated in vitro by proteolysis of
      the cocoa vicilin-class(7S) globulin using a mixture of cocoa aspartic protease
      and cocoa carboxypeptidase. Since both proteases have rather different pH optima
      (pH 3.5 and 5.5-6.0, respectively), we have investigated the pH-dependency of
      proteolysis of this protein substrate in the presence of both proteases, the
      liberation of free amino acids and the generated aroma potential. Our findings
      revealed that the precursors of the nutty aroma notes were generated at higher pH
      values (pH 4.8-5.6) than the cocoa-specific precursor peptides (pH 4.4-5.2).
      Longer peptide fragments of the cocoa vicilin were formed by proteolysis at pH
      5.2 than at pH 4.8. Furthermore, our findings indicated that cocoa-vicilin
      derived peptides are essential precursors of both the cocoa- and the nutty
      specific aroma components.

PMID- 29571469
TI  - Physicochemical and emulsification properties of flaxseed (Linum usitatissimum)
      albumin and globulin fractions.
AB  - The physicochemical and emulsification characteristics of flaxseed albumin and
      globulin protein fractions were determined in this study. Flaxseed protein meal
      was extracted with 0.5 M NaCl, and the extract dialyzed against water followed by
      centrifugation to obtain the globulin as a water-insoluble precipitate and
      albumin as the water-soluble albumin. Gel electrophoresis data indicate that the
      globulin is composed of several polypeptides in the 10-50 kDa range while albumin
      consisted mainly of the 10 kDa polypeptide accompanied by a minor content of 40
      kDa. Amino acid analysis showed significantly (p < 0.05) higher levels of
      hydrophobic amino acids in the globulin, which was consistent with higher surface
      hydrophobicity when compared to the albumin. All the emulsions had monomodal oil
      droplet size distribution and wider ranges were directly related to bigger sizes,
      especially at low (10 mg/mL) protein concentration when compared to the 50 mg/mL.

PMID- 29571470
TI  - Magnetic molecular imprinting polymers based on three-dimensional (3D) graphene
      carbon nanotube hybrid composites for analysis of melamine in milk powder.
AB  - A novel analytical method for melamine in milk powder has been developed and
      exploited with three-dimensional (3D) magnetic molecularly imprinted polymers
      (MMIPs) combining with liquid chromatography-tandem mass spectrometry. The 3D
      MMIPs were synthesized with graphene-carbon nanotube hybrid composite as carrier
      which can increase the accessible surface area. The products were characterized,
      and the binding affinity was investigated by isothermal absorption, kinetic
      adsorption and selective adsorption. The results showed that the 3D MMIPs
      exhibited high adsorption capacity with maximum adsorption capacity of 123.1 mg g
      1, fast adsorption rate (10 min) and high selectivity toward melamine. Various
      affecting extraction parameters were evaluated. The limit of detection was
      0.00045 mg kg-1 and the recoveries were ranged from 90.3% to 95.7%. The
      precisions (RSDs) were lower than 4.7%. This method was applied for analyzing six
      milk powder samples. The result was in agreement with that obtained by the state
      standard method used in China.

PMID- 29571471
TI  - Persimmon vinegar polyphenols protect against hydrogen peroxide-induced cellular
      oxidative stress via Nrf2 signalling pathway.
AB  - Since polyphenols are known to exhibit antioxidative properties, we prepared and
      characterized persimmon vinegar polyphenols (PVP) in this study. Furthermore, we
      investigated the protective effect of PVP on hydrogen peroxide (H2O2)-induced
      oxidative stress in HepG2 cells and its underlying mechanisms. Our results showed
      that flavon-3-ols were the predominant polyphenols in PVP. Pre-treatment with PVP
      significantly decreased (p < 0.05) H2O2-induced cell damage in a dose-dependent
      manner, accompanied by decrease in lactate dehydrogenase (LDH) leakage,
      aminotransferase activities, and ROS accumulation. Moreover, PVP upregulated the
      expression of antioxidative enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H:
      quinone oxidoreductase 1 (NQO1), and increased the levels of glutathione. Western
      blotting results showed that PVP induced the nuclear translocation of nuclear
      factor (erythroid-derived-2)-related factor 2 (Nrf2). Taken together, our results
      indicated that PVP effectively protected HepG2 cells against oxidative stress via
      activation of the Nrf2 antioxidative pathway.

PMID- 29571472
TI  - Determination of ppq-levels of alkylmethoxypyrazines in wine by stirbar sorptive
      extraction combined with multidimensional gas chromatography-mass spectrometry.
AB  - Alkylmethoxypyrazines are powerful odorants in many food products. A new method
      for analysing 3-isopropyl-2-methoxypyrazine, 3-s-butyl-2-methoxypyrazine and 3
      isobutyl-2-methoxypyrazine has been developed and applied to wine. The analytes
      were extracted from 5 mL of wine using stirbar sorptive extraction followed by
      thermal desorption and multidimensional gas chromatography-mass spectrometry
      analysis in a single oven. The extraction conditions were optimized in order to
      obtain a high recovery of the 3-alkyl-2-methoxypyrazines (MP). The detection
      limits of the method in all cases were under 0.08 ng/L, well below the olfactory
      thresholds of these compounds in wine. The reproducibility of the method was
      adequate (below 10%), the linearity satisfactory and the recoveries in all cases
      close to 100%. The method has been applied to the analysis of 111 Spanish and
      French wine samples. The levels found suggest that MP have a low direct impact on
      the aroma properties of wines from the regions around the Pyrenean massif.

PMID- 29571473
TI  - Heat-induced polymerization behavior variation of frozen-stored gluten.
AB  - The current study comparatively investigated the heat-induced polymerization
      behavior of fresh and frozen-stored gluten to replenish the gluten deterioration
      mechanism in frozen dough from the perspective of subsequent polymerization
      behavior during heating. The results showed that disulfide-mediated
      polymerization of frozen-stored gluten upon heating at 95  degrees C was
      suppressed. The polymerization ability of glutenin was weakened rather than
      gliadin for frozen-stored gluten. Enhanced level of beta-structures at the
      expense of alpha-helices was detected during the incipient heating of fresh
      gluten, while converse trend was noticed for the frozen-stored gluten. Frozen
      stored gluten exhibited less exposure of surface hydrophobic groups during the
      initial heating, suggesting that it was less responsive to the unfolding process.
      The weakened viscoelastic properties of frozen-stored gluten throughout heating
      protocols were mainly originated from glutenin macropolymer depolymerization as
      well as the hindered formation of glutenin-gliadin crosslinking and non-covalent
      bonds.

PMID- 29571474
TI  - Kinetic study on photostability of retinyl palmitate entrapped in policosanol
      oleogels.
AB  - Photostability of all-trans retinyl palmitate (RP) (100% bioactivity) was studied
      in policosanol oleogels (PCOs) (7-12% w/w policosanol in soybean oil) after UVA
      irradiation. RP was incorporated into PCOs at levels of 0.04%, 0.1% and 1% (w/w).
      PCOs efficiently protected RP from UVA-mediated degradation. Over 75% RP-activity
      remained in PCOs after 4 days of UVA irradiation, while 12% RP-activity remained
      in soybean oil. HPLC analysis showed that cis-RP was formed in liquid soybean oil
      after 2 days of UVA irradiation while it was absent in PCOs matrices. PCOs
      blocked the energy absorption from UVA and further dampened the UVA-mediated
      ionic photodissociation and free radical reaction due to matrix immobilization.
      For all samples, RP photodegradation followed a 2nd order reaction. From the
      reaction kinetics, it would be possible to predict the RP photodegradation rate
      in PCO matrices. PCOs were shown to be a promising matrix to protect RP from
      photodegradation.

PMID- 29571475
TI  - Gut peptidases from a specialist herbivore of latex plants are capable of milk
      protein hydrolysis: Inputs for hypoallergenic milk formulas.
AB  - Transitory allergies to cow milk proteins in infants or adults have become a
      public health problem. Although extensively or partially hydrolyzed cow milk
      protein formulas are available, these products are costly. Therefore, studies
      into innovative enzymes to digest cow milk proteins are needed. Danaus plexippus
      gut peptidases were purified and examined with regard to cow milk protein
      hydrolysis. The peptidases hydrolyzed caseins and whey proteins. However, after
      heat treatment, there was a significant improvement in beta-lactoglobulin
      hydrolysis. The hydrolyzed cow milk proteins were not recognized by anti-casein
      antibodies and only reacted slightly with antibodies against whey proteins. This
      performance was better than that of partially hydrolyzed formulas and similar to
      that of an extensively hydrolyzed formula. These results suggest that D.
      plexippus gut peptidases are suitable and innovative enzymes to produce
      hypoallergenic cow milk protein formulas.

PMID- 29571476
TI  - Annatto-entrapped casein-chitosan complexes improve whey color quality after acid
      coagulation of milk.
AB  - A fraction of annatto is often transferred to the whey fluid during Cheddar
      cheese processing, which negatively impacts the visual and sensory attributes of
      the resultant whey powder. Alternatives to reduce the color in the powder are
      still needed. In this study, casein-chitosan complexes were prepared to deliver
      annatto preferentially to the curd and reduce the amount of carryover colorant in
      whey powder. These complexes were relatively spherical, with a mean complex
      diameter of 8.3 +/- 1.9 um, zeta-potential of +39.4 +/- 1.3 mV, and entrapment
      efficiency of 38.2 +/- 3.1%. FT-IR spectroscopy confirmed the electrostatic
      interaction between casein and chitosan. Complexes and commercial annatto powder
      were incorporated into homogenized, reduced-fat, and fat-free milk, and subjected
      to acid coagulation. Whey powder produced from casein-chitosan-complex-treated
      samples exhibited better color quality than that prepared with annatto powder,
      indicating that the approach considered in this study was efficient in preventing
      the migration of colorant to the whey.

PMID- 29571477
TI  - Patulin accumulation in apples under dynamic controlled atmosphere storage.
AB  - The goal of this study was to evaluate patulin contamination in 'Galaxy' and
      'Fuji Kiku' apples subjected to controlled atmosphere (CA) and dynamic controlled
      atmosphere (DCA) conditions. Experiments were performed and fruit were stored for
      nine months under refrigeration plus 7 days shelf life at 20  degrees C. CA and
      DCA were not effective in preventing patulin production in either 'Galaxy' or
      'Fuji Kiku' apples. Healthy fruit were not contaminated with patulin, even when
      stored together with decayed apples. For 'Galaxy' apples, application of 1
      methylcyclopropene increased the percentage of fruit with decay and patulin
      contamination. Patulin concentrations were above the maximum limit (50 MUg kg-1)
      established in the Brazilian legislation, meaning the use of CA and DCA
      conditions were not advantageous in preventing patulin accumulation. In 'Fuji
      Kiku' apples, there was no significant difference in patulin concentration among
      CA, DCA-CF and DCA-RQ 1.3 treatments, and all were below the maximum.

PMID- 29571478
TI  - Identification of a precursor of 2-mercapto-3-methyl-1-butanol in beer.
AB  - 2-Mercapto-3-methyl-1-butanol (2M3MB) imparts an onion-like off-flavor to beer
      and is believed to result from the hot aeration of brewer's wort. However, little
      has been reported regarding the mechanism of formation of 2M3MB. This paper
      investigates the precursors of 2M3MB formed during the brewing process. Our study
      of a cysteine conjugate as a precursor showed its negligible contribution to the
      formation of 2M3MB. The 2M3MB precursor was found to be a volatile compound
      because 2M3MB was formed in the distillate of hop extract. The precursor was
      purified through distillation, column chromatography, and preparative gas
      chromatography, and the 2M3MB-producing potential was measured as an index for
      estimating the concentration of the precursor. The accurate mass of the precursor
      was measured using gas chromatography coupled to quadrupole-time-of-flight-mass
      spectrometry (GC/QTOF). The molecular structure was identified from the product
      ion spectra by GC/QTOF to be 2,3-epoxy-3-methylbutanal.

PMID- 29571479
TI  - Combination of sodium caseinate and succinylated alginate improved stability of
      high fat fish oil-in-water emulsions.
AB  - Sodium caseinate (CAS) and commercial sodium alginate (CA), long chain modified
      alginate (LCMA) or short chain modified alginate (SCMA) were used in combination
      for emulsifying and stabilizing high fat (50-70%) fish oil-in-water emulsions.
      Physical (creaming, droplet size, viscosity and protein determination) and
      oxidative (primary and secondary oxidation products) stabilities of the emulsions
      were studied during 12 days of storage. Creaming stability was higher for
      emulsions produced with alginates and CAS compared to emulsions prepared with
      only CAS. Combined use of CAS + LCMA performed better in terms of physical
      stability compared to emulsions produced with only CAS. However, the oxidative
      stability of this emulsion was inferior probably due to the presence of an
      unsaturated carbon chain in LCMA structure. CAS + SCMA emulsions not only showed
      better physical stability such as smaller droplet size, lower creaming and higher
      viscosity, but also had an improved oxidative stability than emulsions produced
      with only CAS.

PMID- 29571480
TI  - Phytochemical profiles, and antimicrobial and antioxidant activities of greater
      galangal [Alpinia galanga (Linn.) Swartz.] flowers.
AB  - Previous studies of galangal (Alpinia galanga) have focussed mostly on rhizomes
      but seldom on flowers. A comprehensive look at galangal flowers could reveal
      additional benefits. The chemical composition of galangal flowers was
      significantly (p < 0.05) different from that of galangal rhizome. Pentadecane and
      alpha-humulene were identified as major compounds of galangal flower essential
      oil. 1'-acetoxyeugenol acetate was identified as the highest compound in flowers
      and exhibited the strongest antimicrobial activity among all fractions, with
      MIC50 values of 34 MUg/ml against Staphylococcus aureus and 68 MUg/ml against
      Listeria monocytogenes. Galangal flowers had a 3-fold higher total phenols
      content than had rhizomes (10.5 vs. 3.33 mg GAE/g powder). The antioxidant
      activities of different flower fractions varied from 2 to 4.45 mmol  trolox/g
      phenolics. These findings suggest that antimicrobial and antioxidant agents
      extracted from galangal flowers could potentially be utilized as natural food
      preservatives or as therapeutic agents.

PMID- 29571481
TI  - Fatty acidomics: Evaluation of the effects of thermal treatments on commercial
      mussels through an extended characterization of their free fatty acids by liquid
      chromatography - Fourier transform mass spectrometry.
AB  - An unprecedented characterization of free fatty acids (FFA) in the lipid extracts
      of fresh or thermally treated mussels of sp. Mytilus galloprovincialis, including
      up to 128 saturated, mono- or poly-unsaturated and 63 oxidized (i.e., modified by
      hydroxylic, carbonylic and/or epoxylic groups) compounds, was achieved using
      reverse phase chromatography coupled to electrospray ionization-Fourier transform
      single and tandem mass spectrometry (RPC-ESI-FTMS,MS/MS). Subsequent Principal
      Components Analysis (PCA) evidenced several effects of thermal treatments on the
      mussel FFA profiles. In particular, death-inducing low temperature treatments
      (freezing at -16  degrees C or refrigeration at 4  degrees C for several days)
      induced a peculiar increase in the incidence of FFA, whereas the effect was
      absent in mussels undergoing death upon prolonged storage at room temperature (25
      degrees C, 6 h) or fast cooking (100  degrees C, 5 min). Alive mussels, either
      fresh or resulting from short term (up to 48 h) refrigeration were actually
      indistinguishable by PCA, although subtle seasonal effects were observed.

PMID- 29571482
TI  - A new method of UA_CPE coupled with spectrophotometry for the faster and cost
      effective detection of proline in fruit juice, honey, and wine.
AB  - The study developed a new method for proline detection in honey, wine and fruit
      juice using ultrasound assisted-cloud point extraction (UA-CPE) and
      spectrophotometry. Initially, a quaternary complex was built, containing proline,
      histamine, Cu(II), and fluorescein at pH 5.5. Samples were treated with ethanol
      water mixture before extraction and preconcentration, using an ultrasonic bath
      for 10 min at 40  degrees C (40 kHz, 300 W). After the optimization of variables
      affecting extraction efficiency, good linearity was obtained between 15 and 600
      ug L-1 with sensitivity enhancement factor of 105. The limits of detection and
      quantification were 5.7 and 19.0 ug L-1, respectively. The recovery percentage
      and relative standard deviations (RSD %) were between 95.3 and 103.3%, and 2.5
      and 4.2%, respectively. The accuracy of the method was verified by the analysis
      of a standard reference material (SRM 2389a).

PMID- 29571483
TI  - Coupling laser desorption with gas chromatography and ion mobility spectrometry
      for improved olive oil characterisation.
AB  - The investigation of volatile compounds in the headspace of liquid samples can
      often be used for detailed and non-destructive characterisation of the sample.
      This has great potential for process control or the characterisation of food
      samples, such as olive oil. We investigated, for the first time, the plume of
      substances released from olive oil droplets by laser desorption in a feasibility
      study and applied ion mobility spectrometry coupled to rapid GC pre-separation to
      enhance selectivity. Our investigation demonstrated that significantly more
      substances can be detected and quantified via laser desorption than in the usual
      headspace, enabling a rapid (5-10 min), sensitive (low ng/g range) and
      comprehensive analysis of the sample, with the potential for quality control and
      fraud identification. Therefore, laser desorption provides a useful sampling tool
      for characterising liquids in many applications, requiring only a few uL of
      sample.

PMID- 29571484
TI  - Nitrogen compounds in Phacelia tanacetifolia Benth. honey: First time report on
      occurrence of (-)-5-epi-lithospermoside, uridine, adenine and xanthine in honey.
AB  - Lacy phacelia (Phacelia tanacetifolia Borkh.) honey composition was screened by
      UHPLC-DAD-QqTOF-MS. The targeted analysis revealed 6 major nitrogen compounds
      including aromatic amino acids (tyrosine, phenylalanine), purine derivatives
      (adenine, xanthine), nucleoside (uridine) and rare non-cyanogenic cyanoglucoside,
      (-)-5-epi-lithospermoside ((2Z)-2-[(4R,5R,6S)-4,5-dihydroxy-6-(beta-d
      glucopyranosyl)oxycyclohex-2-en-1-ylidene]acetonitrile). Their identity was
      confirmed by different analytical tools: HRMS, co-chromatography with standard
      compound or comprehensive NMR experiments. All the compounds, except amino acids,
      were reported and determined in honey for the first time. The amount of the
      compounds was quantified in 16 unifloral phacelia samples: adenine (18.45 +/-
      4.63 mg/kg), xanthine (10.53 +/- 2.98 mg/kg), uridine (42.84 +/- 9.26 mg/kg),
      tyrosine (14.66 +/- 10.22 mg/kg), (-)-5-epi-lithospermoside (70.61 +/- 31.37
      mg/kg) and phenylalanine (20.41 +/- 11.99 mg/kg). The (-)-5-epi-lithospermoside
      content is significantly correlated with P. tanacetifolia pollen percentage (R2 =
      0.5612, p < 0.001) and it is proposed as a potential marker of botanical origin
      for phacelia honey.

PMID- 29571485
TI  - A feasible method for As speciation in several types of seafood by LC-ICP-MS/MS.
AB  - A method for arsenic speciation in shark, shrimp, squid, oyster and scallop using
      liquid chromatography coupled to inductively coupled plasma triple quadrupole
      mass spectrometry (LC-ICP-MS/MS) was proposed. Suitable sensitivity and
      selectivity by LC-ICP-MS/MS were obtained using 10 mmol L-1 (NH4)2HPO4 diluted in
      1% methanol (pH 8.65) as mobile phase. Recoveries from 90 to 104% for
      arsenobetaine (AsB), arsenite [As(III)], dimethylarsinic acid (DMA),
      monomethylarsonic acid (MMA) and arsenate [As(V)] were obtained for all samples.
      A certificated reference material was also analyzed and the sum of As species was
      in agreement with the total As concentration. Limits of quantification (LOQ) for
      AsB, As(III), DMA, MMA, and As(V) were 6, 30, 6, 12 and 26 ng g-1, respectively.
      Higher concentration of AsB was found in all seafood, while As(III) and DMA were
      found only in oyster. Arsenate was found in squid and scallops, and MMA was below
      the LOQ in all samples.

PMID- 29571486
TI  - Caramel colour and process by-products in foods and beverages: Part I -
      Development of a UPLC-MS/MS isotope dilution method for determination of 2-acetyl
      4-(1,2,3,4-tetrahydroxybutyl)imidazole (THI), 4-methylimidazole (4-MEI) and 2
      methylimidazol (2-MEI).
AB  - Caramel colours are used by the food industry in a wide range of foods and
      beverages. During their manufacturing, low molecular weight compounds such as 4
      methylimidazole (4-MEI), the structural isomer of 4-MEI, 2-methylimidazole (2
      MEI) and 2-acetyl-4-tetrahydroxy-butylimidazole (THI) are generated. The presence
      of these inevitable by-products of caramel manufacturing can be hazardous to
      human health. This publication describes an isotope dilution Ultra-High
      performance Liquid Chromatography tandem mass spectrometric method (UHPLC-MS/MS)
      that was developed and validated for the simultaneous quantification of these
      impurities in both beverages/liquids and foods. A limit of quantification of 5
      MUg/kg was obtained for 4-MEI and THI. The expanded measurement uncertainty (U; k
      = 2) for these compounds was below 51% in beverages/liquids and below 56% in
      foods. As higher measurement uncertainties were obtained for 2-MEI, the developed
      analytical procedure can only be used in a semi-quantitative way for this
      compound.

PMID- 29571487
TI  - Deep eutectic solvent-based valorization of spent coffee grounds.
AB  - Spent coffee grounds (SCGs) are viewed as a valuable resource for useful
      bioactive compounds, such as chlorogenic acids and flavonoids, and we suggest an
      eco-friendly and efficient valorization method. A series of choline chloride
      based deep eutectic solvents (DESs) were tested as green extraction solvents for
      use with ultrasound-assisted extraction. Extraction efficiency was evaluated
      based on total phenolic content (TPC), total flavonoid content, total chlorogenic
      acids, and/or anti-oxidant activity. A binary DES named HC-6, which was composed
      of 1,6-hexanediol:choline chloride (molar ratio 7:1) was designed to produce the
      highest efficiency. Experimental conditions were screened and optimized for
      maximized efficiency using a two-level fractional factorial design and a central
      composite design, respectively. As a result, the proposed method presented
      significantly enhanced TPC and anti-oxidant activity. In addition, phenolic
      compounds could be easily recovered from extracts at high recovery yields (>90%)
      by adsorption chromatography.

PMID- 29571488
TI  - Heavy metal content and element analysis of infant formula and milk powder
      samples purchased on the Tanzanian market: International branded versus black
      market products.
AB  - Milk powder is a food for malnourished African children and for healthy infants
      of women with HIV/AIDS. High demand and low purchasing power has resulted in a
      huge informal, black market in Sub-Saharan Africa. Forty-three milk powder
      batches were analyzed for 43 chemical elements using ICP-MS One sample (2.3%) was
      contaminated at a lead concentration of 240 ug/kg dry weight exceeding the
      European threshold (130 ug/kg dry weight). Macroelement contents revealed a trend
      decreasing in concentration through skimmed, full cream products to infant
      formulae. Concentration ranges by dry weight differed in respect of uncertainty
      intervals of  +/-10%. Median Ca, K and P concentrations declined from 11.14 g/kg
      to 3.21 g/kg, 14.11 g/kg to 4.95 g/kg and 9.12 g/kg to 2.75 g/kg dry mass,
      respectively. Milk powder samples obtained from the Tanzanian black market were
      comparable in respect of nutritional and chemical content to international
      branded full cream products.

PMID- 29571489
TI  - Caramel colour and process contaminants in foods and beverages: Part II -
      Occurrence data and exposure assessment of 2-acetyl-4-(1,2,3,4
      tetrahydroxybutyl)imidazole (THI) and 4-methylimidazole (4-MEI) in Belgium.
AB  - In Europe, 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) and 4
      methylimidazole (4-MEI) are - to a certain level - allowed to be present in the
      food colours ammonia caramel (E 150c) and sulphite ammonia caramel (E 150d).
      Besides their presence in food colours, exposure to these contaminants may also
      include other dietary sources. This study describes the occurrence of THI and 4
      MEI in a wide variety of food products (n = 522) purchased from the Belgian
      market and their dietary intake in Belgian consumers from 15 years old onwards.
      THI was found to be present in 22.4% of the investigated foods at a level up to
      551 ug/kg. For 4-MEI (57.7% quantifiable), concentrations up to 2,835 ug/kg were
      observed. The average dietary intake amounted to 0.02-0.36 ug kg-1 bw-1 day for
      THI and 0.4-3.7 ug kg-1 bw-1 day for 4-MEI. Coffee, cola and beer were
      contributing most to the dietary THI and 4-MEI intake in Belgium.

PMID- 29571490
TI  - Enzyme immunoassay (ELISA/immunosensor) for a sensitive detection of pork
      adulteration in meat.
AB  - ELISA/immunosensor were developed for a sensitive detection of pork adulteration
      in meat. Two formats of ELISA were performed. First, an extracted IgG was
      directly immobilized in the microplate. This assay allowed an identification of
      0.01% as level of pork adulteration in 14 h15 min. In order to decrease the time
      of the assay, a competitive ELISA was developed by immobilizing IgG standard,
      which compete with the extracted IgG. This assay allowed a detection of 0.1% of
      pork adulteration in 45 min. Furthermore, two formats of electrochemical
      immunosensors were elaborated using the electro-entrapment of IgG in polymer
      modified graphite paste electrode. First, a direct immunosensor was capable of
      identifying 0.1 and 1% in raw and cooked meat respectively in 2 h. The second
      format was based on a competitive immunosensor, which was able to detect 0.01% of
      pork adulteration within 20 min. Both competitive immunoassays revealed high
      sensitivity, good specify and reduced analysis time.

PMID- 29571491
TI  - Ethanol-induced composite hydrogel based on propylene glycol alginate and zein:
      Formation, characterization and application.
AB  - A novel ethanol-induced composite hydrogel was prepared by two edible
      biopolymers: propylene glycol alginate (PGA) and zein. The effect of pH and
      different mass ratios of PGA and zein on the properties of the composite hydrogel
      was investigated. PGA and zein could form a gel induced by ethanol at pH >= 3.5,
      the stability, springiness, hardness and water holding capacity were decreased
      from pH 3.5 to 5.0. The hydrogen-bonding association was enhanced at pH 3.5 and
      porous structure was observed. The strength and springiness of the composite
      hydrogel decreased with increasing concentration of zein until the PGA/zein mass
      ratio was 5:1. At PGA/zein mass ratio of 5:1, the composite hydrogel exhibited a
      more elastic and tougher structure than other mass ratios at pH 3.5. Meanwhile,
      compared with the PGA hydrogel, the PGA-zein composite hydrogel showed great
      ability to sustain the release of curcumin in simulated gastrointestinal tract
      conditions.

PMID- 29571492
TI  - First evaluation of drug-in-cyclodextrin-in-liposomes as an encapsulating system
      for nerolidol.
AB  - Nerolidol, a naturally occurring sesquiterpene with antimicrobial activities, is
      a promising candidate as a natural alternative for synthetic preservatives in
      food. However, its application is limited by low aqueous solubility and
      stability. In this study, conventional liposomes and drug-in-cyclodextrin-in
      liposomes (DCLs) were evaluated for the first time as encapsulating materials for
      nerolidol. The size, encapsulation efficiency (EE%), loading rate (LR%), photo-
      and storage stabilities of both systems were characterized. Moreover, the in
      vitro release of nerolidol from liposomes and DCLs was investigated over time.
      Nerolidol was efficiently entrapped in both carriers with high EE% and LR%
      values. In addition, DCLs prolonged the release of nerolidol over one week and
      enhanced the photostability more effectively than conventional liposomes.
      Finally, all formulations were stable after 12 months of storage at 4  degrees C
      (>60% incorporated nerolidol). Therefore, DCLs are promising carriers for new
      applications of sesquiterpenes in the pharmaceutical and food industries.

PMID- 29571493
TI  - A low trans margarine fat analog to beef tallow for healthier formulations:
      Optimization of enzymatic interesterification using soybean oil and fully
      hydrogenated palm oil.
AB  - The health hazard of tallow and partial hydrogenated oils is well known in
      margarine productions. For this, food manufactures are urged to develop novel
      alternatives for healthier margarine formulations. The highest
      interesterification degree acquired with lipase Lipozyme 435 standing out from
      other catalysts (solid acid, sodium hydroxide and methoxide) was applied to
      produce low trans margarine fat analogs to beef tallow (BT) with the blend of
      soybean oil (SO) and fully hydrogenated palm oil (FHPO) in a mass ratio of 4:3.
      Reaction parameters like enzyme dosage (4.2 wt%), temperature (95  degrees C) and
      time (245 min) were optimized using the Box-Behnken design. Regarding fatty acid
      profiles, triacylglycerol species, solid fat content, polymorphism, melting and
      crystallization behaviors, the resulting interesterified oil was characterized in
      comparison with BT, FHPO and the SO-FHPO blend so as to prove its potential in
      formulating low trans fat margarines because of desirable physicochemical
      properties and polymorphs.

PMID- 29571494
TI  - A new formaldehyde sensor from silver nanoclusters modified Tollens' reagent.
AB  - A selective colorimetric assay for detecting formaldehyde (FA) was proposed based
      on silver nanoclusters (AgNCs) templated by polymethacrylic acid (PMAA). The
      chemodosimeter was easily fabricated by the formation of Tollens' reagent in the
      presence of AgNCs (AgNCs@Tollens). The detection principle was based on the
      change in the color caused by the change in the particle size from nanoclusters
      (no LSPR) to nanoparticles (with LSPR) upon the reduction of Tollens' reagent by
      FA. In the presence of FA, the intensity of a new absorbance band with a maximum
      at a wavelength of 430 nm corresponding to the LSPR of the AgNPs linearly
      increased as a function of the FA concentration, exhibiting a color change that
      could be observed by the naked eye. This method provided a working range of 30-50
      uM with lower detection limit (LOD) of 27.99 uM. The proposed method exhibited
      excellent selectivity towards FA over other aldehyde-containing compounds.

PMID- 29571495
TI  - Impact of roasting on the flavan-3-ol composition, sensory-related chemistry, and
      in vitro pancreatic lipase inhibitory activity of cocoa beans.
AB  - Roasting is an important cocoa processing step, but has been reported to reduce
      the polyphenol content in the beans. We investigated the impact of whole-bean
      roasting on the polyphenol content, aroma-related chemistry, and in vitro
      pancreatic lipase (PL) inhibitory activity of cocoa under a range of roasting
      conditions. Total phenolics, (-)-epicatechin, and proanthocyanidin (PAC) dimer -
      pentamer content was reduced by roasting. By contrast, roasting at 150  degrees C
      or greater increased the levels of catechin and PAC hexamers and heptamers. These
      compounds have greater PL inhibitory potency. Consistent with these changes in
      PAC composition and this previous data, we found that roasting at 170  degrees C
      time-dependently increased PL inhibitory activity. Cocoa aroma-related compounds
      increased with roasting above 100  degrees C, whereas deleterious sensory-related
      compounds formed at more severe temperatures. Our results indicate that cocoa
      roasting can be optimized to increase the content of larger PACs and anti-PL
      activity, while maintaining a favorable aroma profile.

PMID- 29571496
TI  - Fluoroimmunoassays for the detection of zearalenone in maize using CdTe/CdS/ZnS
      quantum dots.
AB  - CdTe/CdS/ZnS quantum dots (QDs) were synthesized in aqueous phase and conjugated
      with a new anti-zearalenone (ZEN) monoclonal antibody. Using this novel
      fluorescent probe, a fluoroimmunoassay (FLISA) and a rapid immunochromatographic
      strip (ICTS) were developed for the detection of ZEN in maize. Our proposed FLISA
      allowed for ZEN determination in the range of 0.038-0.977 ng/mL with an IC50 of
      0.162 ng/mL and a limit of detection (LOD) of 0.012 ng/mL occurring in maize. The
      rapid ICTS had a visual LOD of 1.0 ng/mL in buffer solution and 1.5 ng/mL in
      maize extract. These two QDs-based immunoassays were all successfully verified by
      commercial ELISA kits. The results confirmed that: firstly, the FLISA can be used
      as a robust method for the sensitive detection of ZEN; and secondly, the ICTS is
      ideally suited for rapidly screening large numbers of samples.

PMID- 29571497
TI  - Influence of indigenous minor components on fat crystal network of fully
      hydrogenated palm kernel oil and fully hydrogenated coconut oil.
AB  - Purification of triglycerides from fully hydrogenated palm kernel oil (FHPKO) and
      fully hydrogenated coconut oil (FHCNO) was performed by a chromatographic method.
      Lipid composition, thermal properties, polymorphism, isothermal crystallization
      behaviour, nanostructure and microstructure of FHPKO, FHPKO-triacylglycerol
      (TAG), FHCNO and FHCNO-TAG were evaluated. Removal of minor components had no
      effect on triglycerides composition. However, the presence of the minor
      components did increase the slip melting point and promote onset of
      crystallization. Furthermore, the thickness of the nanoscale crystals increased,
      and polymorphic transformation from beta' to beta occurred in FHPKO after the
      removal of minor components, and from alpha to beta' in FHCNO. Sharp changes in
      the values of the Avrami constant K and exponent n suggested that the presence of
      minor components changed the crystal growth mechanism. The PLM results indicated
      that a coarser crystal structure with lower fractal dimension appeared after the
      removal of minor components from both FHPKO and FHCNO.

PMID- 29571498
TI  - Chemical, sensory, and functional properties of whey-based popsicles manufactured
      with watermelon juice concentrated at different temperatures.
AB  - The effects of the concentration of watermelon juice at different temperatures
      (45, 55, or 65  degrees C) on the physicochemical and sensory characteristics,
      antioxidant capacity, and volatile organic compounds (VOCs) of whey-based
      popsicles were investigated. Total phenolic content, lycopene, citrulline, VOCs,
      melting rate, instrumental colour, antioxidant capacity, and the sensory
      characteristics (hedonic test and free listing) were determined. The temperature
      led to a significant decrease in bioactive compounds (total phenolics, lycopene,
      and citrulline). The popsicle manufactured with reconstituted watermelon juice
      concentrated to 60  degrees Brix at 65  degrees C presented higher antioxidant
      capacity and was characterized by the presence of alcohols, aldehydes and ketones
      and presented a similar acceptance to the untreated popsicle (except for
      flavour). It is possible to combine whey and concentrated watermelon juice for
      the manufacture of bioactive-rich popsicles, using the concentration temperature
      of 65  degrees C as a suitable processing condition for potential industrial
      applications.

PMID- 29571499
TI  - Formulation and characterization of astaxanthin-enriched nanoemulsions stabilized
      using ginseng saponins as natural emulsifiers.
AB  - In this study ginseng saponins (GS) were used as natural emulsifiers to formulate
      and stabilize O/W nanoemulsions loaded with astaxanthin (AST). GS were found to
      be highly effective at reducing the interfacial tension at the soybean oil-water
      interfaces, and were capable of producing nano-scaled droplets (d4,3 ~ 125 nm)
      using a high-pressure homogenizer. The droplet size of the nanoemulsions
      decreased with increasing emulsifier concentration and homogenization pressure.
      The nanoemulsions were stable without droplet coalescence against thermal
      treatment (30-90  degrees C, 30 min), and over a narrow range of pH values (7-9).
      GS-coated droplets were unstable in acidic conditions (pH 3-6) and in the
      presence of salt (>25 mM NaCl). The formulated nanoemulsions showed slight change
      in d4,3 during 15 days of storage at 5, 25 and 40  degrees C. However, the
      chemical stability strongly depended on the storage temperature, with the lowest
      level of AST retained in nanoemulsions stored at higher temperature.

PMID- 29571500
TI  - Development of pure certified reference material of stevioside.
AB  - Pure stevioside was extracted from leaves of Stevia rebaudiana (Bertoni) to be
      used as a reference material in the instrument calibration or method validation
      process. The mass fraction was determined by comparison between the mass balance
      method and quantitative nuclear magnetic resonance (qNMR) spectroscopy. The
      impurities in the sample were analyzed by Karl Fischer titration for moisture
      content and thermogravimetric analysis for inorganic residue. Homogeneity,
      together with short term and long term stability, were also studied and the
      uncertainty was reported. The certified value of this mass fraction is 0.986 +/-
      0.0019 (k = 2) with 1 year stability.

PMID- 29571501
TI  - A study on interactions between the insoluble fractions of different coffee
      infusions and major cocoa free antioxidants and different coffee infusions and
      dark chocolate.
AB  - This study aimed to investigate the interactions between insoluble fractions of
      different coffee infusions and major cocoa free antioxidants, catechin and
      epicatechin, as well as the interactions between different coffee infusions and
      dark chocolate. Espresso, filtered coffee, French press and Turkish coffee were
      used for this purpose. Antioxidant capacity (AC) measurements were performed by
      monitoring the percentage inhibition of 2,2-Diphenyl-1-picrylhydrazil (DPPH)
      radical. Multivariate approach was adopted for experimental design and data
      analysis steps. In dry basis, the AC values of infusions (mmol Trolox/kg) were
      ranged between 953 +/- 2.6 and 1184 +/- 11.3, while the AC values for their
      insoluble fractions were ranged between 45 +/- 0.0 and 105-1.3. Interactions
      between the insoluble fractions of coffee infusions and catechins were
      synergistic for espresso and additive/antagonistic for the other infusions.
      Interactions between coffee infusions and chocolate were synergistic for French
      press and Turkish coffee and additive/antagonistic for the other infusions.

PMID- 29571502
TI  - Application of magnetic molecularly imprinted polymers for extraction of
      imidacloprid from eggplant and honey.
AB  - A magnetic molecularly imprinted polymer (MMIP) adsorbent for imidacloprid was
      prepared using non-covalent approach with functionalized nano Fe3O4 particles
      (magnetic cores), imidacloprid (template), acrylic acid (functional monomer),
      ethylene glycol dimethacrylate (cross linker) and azobisisobutyronitrile
      (initiator) and used for selective separation of imidacloprid from honey and
      vegetable samples. The polymers were characterized using FT-IR spectroscopy, SEM
      and TEM images. For analysis of imidacloprid LC-MS/MS equipment was used.
      Adsorption kinetics was best explained by pseudo-second-order kinetic model.
      Adsorption data fitted well into linearized Freundlich equation (R2 > 0.98).
      Scatchard plot analysis indicates the presence of two classes of binding sites in
      the MMIPs with the Cmax of 1889.6 ug g-1 and 65448.9 ug g-1, respectively. MMIPs
      demonstrated much higher affinity for imidacloprid over structurally similar
      analogues acetamiprid (alpha = 23.59) and thiamethoxam (alpha = 17.15). About
      87.1 +/- 5.0% and 90.6 +/- 5.6% of the added imidacloprid was recovered from
      MMIPs in case of fortified eggplant and honey samples, respectively.

PMID- 29571503
TI  - Functional attributes of a new molecule-2-hydroxymethyl-benzoic acid 2'-hydroxy
      tetradecyl ester isolated from Talaromyces purpureogenus CFRM02.
AB  - An account of antioxidant and antimicrobial characteristics displayed by ethyl
      acetate extract of Talaromyces purpureogenus CFRM-02 cultivated by submerged
      fermentation on bengal gram husk (BegH) led to the isolation of a new molecule,
      which was purified via silica gel column chromatography. The TLC and HPLC data
      revealed the purity of the isolated compound. By employing an array of
      spectroscopic techniques, structural elucidation was accomplished, and the
      molecule was identified as 2-hydroxymethyl-benzoic acid 2'-hydroxy-tetradecyl
      ester and was also designated with a familiar name pentalsamonin. The
      pentalsamonin molecule scavenged DPPH (24%), H2O2 (64%), superoxide anion (58%)
      with a reducing power (0.989 AU) at the given concentration. The MIC and MBC of
      pentalsamonin against Bacillus subtilis, Staphylococcus aureus, Escherichia coli
      and Klebsiella pneumoniae are in the range 62.5-125 and 125-250 ug/ml,
      respectively. The antioxidant and antibacterial functional attributes of
      pentalsamonin suggest useful applications in food and nutraceuticals.

PMID- 29571504
TI  - Reverse micelles as nanocarriers of nisin against foodborne pathogens.
AB  - Reverse micelles (RMs) as nanocarriers of nisin were optimized for the highest
      water and bacteriocin content. RMs formulated with either refined olive oil or
      sunflower oil, distilled monoglycerides, ethanol, and water were effectively
      designed. Structural characterization of the RMs was assessed using Electron
      Paramagnetic Resonance Spectroscopy and Small Angle X-ray Scattering in the
      presence and absence of nisin. No conformational changes occurred in the presence
      of nisin for the nanocarriers. To assess efficacy of the loaded systems, their
      antimicrobial activity against Staphylococcus aureus and Listeria monocytogenes
      was tested in lettuce leaves and minced meat, respectively. Antimicrobial
      activity was evident in both cases. Interestingly, a synergistic antimicrobial
      effect was observed in lettuce leaves and to a lesser extent in minced meat
      between nisin and some of the nanocarriers' constituents (probably ethanol). Our
      findings suggest complex interactions that take place when RMs are applied in
      different food matrices.

PMID- 29571505
TI  - Screening thresholds: one size does not fit all.

PMID- 29571506
TI  - Gout: a patrician malady no more.

PMID- 29571507
TI  - Once-daily, modified-release hydrocortisone in patients with adrenal
      insufficiency.

PMID- 29571508
TI  - Once-daily, modified-release hydrocortisone in patients with adrenal
      insufficiency.

PMID- 29571509
TI  - Once-daily, modified-release hydrocortisone in patients with adrenal
      insufficiency - Authors' reply.

PMID- 29571510
TI  - Research digest: updates on diabetes in pregnancy.

PMID- 29571511
TI  - Juleen Zierath: in pursuit of curiosity.

PMID- 29571512
TI  - Immunogenicity of PtpA secreted during Mycobacterium avium ssp. paratuberculosis
      infection in cattle.
AB  - AIMS: Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent
      of Johne's disease. To survive within host macrophages, the pathogen secretes a
      battery of proteins to interfere with the immunological response of the host. One
      of these proteins is tyrosine phosphate A (PtpA), which has been identified as a
      secreted protein critical for survival of its close relative M. tuberculosis
      within infected macrophages. METHODS AND RESULTS: In this study, the immune
      response to recombinant PtpA used as an antigen was investigated in a cohort of
      ~1000 cows infected with MAP compared to negative control animals using ELISA.
      The sera from MAP-infected cows had significantly higher levels of antibodies
      against PtpA when compared to uninfected cows. CONCLUSIONS: The data presented
      here indicate that the antibodies produced against PtpA are sensitive enough to
      detect infected animals before the appearance of the disease symptoms.
      SIGNIFICANCE AND IMPACT OF STUDY: The use of PtpA as an antigen can be developed
      as an early diagnostic test. Moreover, PtpA is a candidate antigen for detection
      of humoral immune responses in cows infected with MAP.

PMID- 29571514
TI  - Development and characterization of monoclonal antibodies against canine PD-1 and
      PD-L1.
AB  - Recent research has focused on immunotherapy, particularly with regard to cancer
      treatment. Programmed death-1 and programmed death ligand 1 (PD-1/PD-L1) pathway
      blockade is a central topic of the promising immunotherapy field. In veterinary
      medicine, observations of the PD-1/PD-L1 pathway, including the relationship
      between immune cells and diseases, have increased. In this study, monoclonal
      antibodies specific to canine PD-1 and PD-L1 were developed, and the antibodies
      against PD-1 and PD-L1 bind to PD-1 and PD-L1 overexpressing cells, respectively.
      Additionally, each antibody interfered with the interaction between PD-1 and PD
      L1. The expression of PD-1 and PD-L1 was detected on activated T cells from
      canine peripheral blood mononuclear cells (PBMC), and, remarkably, was the first
      recorded instance of PD-L1 expression on canine immature dendritic cells.
      Production of IFN-gamma by activated T cells increased significantly when
      incubated with anti-PD-1 antibody alone and with both anti-PD-1 and anti-PD-L1
      antibodies, revealing the functional effects of the antibodies. The antibodies
      will be useful for research on immune systems and may be the first passive
      immunotherapy approach in canine cancer patients.

PMID- 29571513
TI  - Seroprevalence for Brucella spp. in Baltic ringed seals (Phoca hispida) and East
      Greenland harp (Pagophilus groenlandicus) and hooded (Cystophora cristata) seals.
AB  - Zoonotic infections transmitted from marine mammals to humans in the Baltic and
      European Arctic are of unknown significance, despite given considerable potential
      for transmission due to local hunt. Here we present results of an initial
      screening for Brucella spp. in Arctic and Baltic seal species. Baltic ringed
      seals (Pusa hispida, n = 12) sampled in October 2015 and Greenland Sea harp seals
      (Pagophilus groenlandicus, n = 6) and hooded seals (Cystophora cristata, n = 3)
      sampled in March 2015 were serologically analysed for antibodies against Brucella
      spp. The serological analyses were performed using the Rose Bengal Test (RBT)
      followed by a confirmatory testing of RBT-positive samples by a competitive
      enzyme linked immunosorbent assay (C-ELISA). Two of the Baltic ringed seals (a
      juvenile male and a juvenile female) were seropositive thus indicating previous
      exposure to a Brucella spp. The findings indicate that ringed seals in the Baltic
      ecosystem may be exposed to and possibly infected by Brucella spp. No
      seropositive individuals were detected among the Greenland harp and hooded seals.
      Although our initial screening shows a zoonotic hazard to Baltic locals, a more
      in-depth epidemiological investigation is needed in order to determine the human
      risk associated with this.

PMID- 29571515
TI  - CK-2 of rainbow trout (Oncorhynchus mykiss) has two differentially regulated
      alleles that encode a functional chemokine.
AB  - Rainbow trout chemokine 2 (CK-2) is currently the only known CC chemokine to have
      a mucin stalk. Further analysis of the mucin stalk region revealed a second,
      related CC chemokine sequence, denoted here as CK-2.1. This second sequence was
      determined to be an allele of CK-2 following genomic PCR analysis on several
      outbred individuals. Furthermore, in both in vivo and in vitro trials, CK-2 and
      CK-2.1 were both present, but appeared to have differential tissue expression in
      both control and PHA stimulated samples. Upon the development of a polyclonal
      antibody to rCK-2, CK-2 was only observed in the brain, liver and head kidney of
      PHA stimulated rainbow trout tissues. In comparison, when using the rainbow trout
      monocyte/macrophage-like cell line, RTS-11, CK-2 protein was observed in both
      control and PHA stimulated conditions. When studying the function of CK-2, a
      chemotaxis assay revealed that both peripheral blood leukocytes and RTS-11 cells
      migrated towards rCK-2 significantly at all concentrations studied when compared
      to truncated beta2m. Interestingly, this migration was lowest at both the highest
      concentration and the lowest concentrations of CK-2. Thus, teleostean chemokine
      receptors may become desensitized when overstimulated as has been observed in
      mammalian models. The observed chemotactic function was indeed due to rCK-2 as
      cell migration was inhibited through pre-treatment of both the cells and the
      polyclonal antibody with rCK-2. As has been observed thus far with all other
      chemokines, CK-2 does appear to function through binding to a G-coupled protein
      receptor as chemotaxis could be inhibited through pre-treatment with pertussis
      toxin. Overall, the results of this study indicate that CK-2 is a functional
      chemokine that is encoded by two differentially expressed alleles in rainbow
      trout, CK-2 and CK-2.1.

PMID- 29571516
TI  - Low pathogenic avian influenza virus infection increases the staining intensity
      of KUL01+ cells including macrophages yet decrease of the staining intensity of
      KUL01+ cells using clodronate liposomes did not affect the viral genome loads in
      chickens.
AB  - The effect of depletion of macrophages using clodronate liposomes as well as
      macrophage response following viral infections have been studied in various mouse
      virus infection models, but they have not been extensively studied in chickens
      relevant to virus infections. When we infected day 6 chickens with H4N6 low
      pathogenic avian influenza virus (LPAIV), we observed that H4N6 LPAIV infection
      increased the staining intensity of KUL01+ cells in trachea, lungs and duodenum
      of chickens at 3 days post-infection. Then, we used clodronate liposomes intra
      abdominally in 5 day-old chickens and found significant reduction of staining
      intensity of KUL01+ cells in trachea and duodenum but not in lungs at 4 days post
      treatment. When we infected the clodronate liposome and PBS liposome treated
      chickens with H4N6 LPAIV intra-nasally at day 6, we found no effect on H4N6 LPAIV
      genome loads in trachea, lungs and duodenum of chickens. This study indicates
      that although KUL01+ cell intensity are increased in respiratory and
      gastrointestinal tissues in chickens following H4N6 LPAIV infection, the decrease
      of KUL01+ cell intensity using clodronate liposomes did not change the H4N6 LPAIV
      genome loads in any of the examined tissues suggesting that KUL01+ cells may not
      be critical during H4N6 LPAIV infection in chicken.

PMID- 29571517
TI  - Evaluation of immune responses in mice and sheep inoculated with a live
      attenuated Brucella melitensis REV1 vaccine produced in bioreactor.
AB  - The Brucella melitensis REV1 vaccine is the most widely employed vaccine for
      prophylaxis against brucellosis in sheep and goats. The objective of vaccination
      is disease control in herds or preventing infection in farms. In this study, we
      produced REV1 vaccine with a protocol, based on the use of liquid medium in a
      bioreactor, that resulted efficient, safe, relatively fast, and cost-effective.
      The live attenuated vaccine produced was tested in mice and sheep to investigate
      its immunogenicity and efficacy. Seventy-two female BALB/c mice were obtained and
      subdivided in 2 groups, one was stimulated with 1 * 106 colony-forming units
      (CFUs) of B. melitensis while the other with physiological solution alone and
      acting as control group. Furthermore, 25 sheep were subdivided into 5 groups:
      four were inoculated with a B. melitensis dose, ranging from 0.6 * 109 and 3.2 *
      109 CFUs and the other was the control group. In addition, a serological
      diagnosis was performed for sheep by rapid serum agglutination and the complement
      fixation test. Immunocompetent cells from both experiment were collected at
      different times post vaccination and immunostained to evaluate innate and
      adaptive-immune responses. In mice flow cytometry was used to detect macrophages,
      T lymphocytes, dendritic cells, memory cells, naive cells, natural killer cells,
      major histocompatibility complex type II, B lymphocytes, regulatory T
      lymphocytes, T helper lymphocytes, cytotoxic T lymphocytes and recently activated
      CD4+ and CD8+ lymphocytes. In sheep, macrophages, T helper cells, cytotoxic T
      lymphocytes, regulatory T lymphocytes, dendritic cells, memory cells and naive
      lymphocytes, by the same method, were analyzed. The results showed, both in mice
      and sheep, that the live, attenuated REV1 vaccine stimulated all immunocompetent
      cells tested, with a balanced innate and adaptive response. In the sheep
      experiment, the administered vaccine dose was very important because, at the
      lower doses, immunological tolerance tended to disappear, while, at the highest
      dose, the immunological tolerance remained active for a long period. In our
      experimental conditions, the optimal vaccine dose for sheep was 3.2 * 109 CFUs,
      although a good immune response was found using a dose of 1.6 * 109 CFUs. The
      vaccine produced in this study could be extensively employed in developing
      countries to control the brucellosis in sheep and goats.

PMID- 29571518
TI  - Matrix metalloproteinases expression in spontaneous canine histiocytic sarcomas
      and its xenograft model.
AB  - Canine histiocytic sarcoma (HS) represents a malignant neoplastic disorder often
      with a rapid and progressive clinical course. A better understanding of the
      interaction between tumor cells and the local microenvironment may provide new
      insights into mechanisms of tumor growth and metastasis. The influence of matrix
      metalloproteinases (MMPs) and their inhibitors (TIMPs) on tumor angiogenesis,
      invasion and metastasis has been detailed in previous studies. In addition,
      inflammatory cells infiltrating neoplasms especially tumor associated macrophages
      (TAM) may contribute significantly to tumor progression. Due to the high
      variability of spontaneously occurring canine HS, standardized models are highly
      required to investigate tumor progression and interaction with its
      microenvironment. Therefore, the present study comparatively characterized the
      intratumoral macrophage infiltration as well as the expression of MMP-2, MMP-9,
      MMP-14 and TIMP-1 in spontaneous canine HS and its murine model. In spontaneous
      canine HS, scattered MAC 387-positive macrophages were randomly found in tumor
      center and periphery, whereas tumor cells were negative for this marker.
      Interestingly, quantitative analysis revealed that MMPs and TIMP-1 were mainly
      expressed at the invasive front while tumor centers exhibited significantly
      reduced immunoreactivity. Similar findings were obtained in xenotransplanted HS.
      Interestingly, murine tumor associated macrophages (TAM), characterized by Mac3
      expression (CD107b/LAMP2), which was not present in xenotransplanted histiocytic
      sarcoma cells, strongly express MMPs and TIMP-1. In addition, MMPs are known to
      regulate angiogenesis and a positive correlation between MMP-14 expression and
      microvessel density was demonstrated in xenotransplanted histiocytic sarcomas.
      Summarized similar findings with respect to MMP and TIMP distribution and the
      role of macrophages in spontaneously-occurring and xenotransplanted HS indicate
      the high suitability of this murine model to further investigate HS under
      standardized conditions. Moreover results indicate that MMP expression
      contributes to tumor progression and invasion and TAMs seem to be major players
      in the interaction between neoplastic cells, the microenvironment and vessel
      formation indicating that therapeutic approaches modulating TAM associated
      molecules might represent promising future treatment options.

PMID- 29571519
TI  - Generation and validation of novel anti-bovine CD163 monoclonal antibodies ABM
      1A9 and ABM-2D6.
AB  - The scavenger receptor CD163 is widely used as a cell signature for alternatively
      active "M2" macrophages in mammals. In this study, we generated two monoclonal
      antibodies, ABM-1A9 and ABM-2D6, against the extracellular region of bovine
      CD163. Conventional Western blotting using the antibodies yielded immunoreactive
      bands of bovine CD163 at 130 and 150 kDa in non-reduced and reduced spleen
      lysates, respectively. The minimum limit of detectable concentration of both
      antibodies was relatively lower (5.0 ng/mL) than that of the anti-human CD163
      monoclonal antibody AM-3 K (>1.0 MUg/mL), which has been used previously for the
      detection of bovine CD163. An immunohistochemical study using formalin-fixed
      paraffin-embedded sections revealed that ABM-1A9 and ABM-2D6 clearly stained some
      Iba1+ macrophages in the lymph nodes of cattle with mastitis. Moreover, the CD163
      stained macrophages were frequently observed engulfing leukocytes. ELISA using
      ABM-2D6 distinguished levels of circulating soluble CD163 in healthy cattle (less
      than 16.9 pmol/mL) and cattle with mastitis (more than 33.7 pmol/mL). These new
      monoclonal antibodies can be used in the diagnosis and evaluation of inflammatory
      disease prognosis in cattle with immunohistological analyses and blood test
      applications.

PMID- 29571520
TI  - Changes in serum anti-Leishmania antibody concentrations measured by time
      resolved immunofluorometric assays in dogs with leishmaniosis after treatment.
AB  - The aim of this study was to evaluate the changes in anti-Leishmania IgG2 and IgA
      antibodies measured by two time-resolved immunofluorometric assays (TR-IFMAs)
      recently validated and by means of a commercially available ELISA test in dogs
      with leishmaniosis after treatment. Serum samples from 16 dogs with clinical
      leishmaniosis were obtained on days 0, 30 and 180 of treatment. In addition,
      these serological changes were compared with the clinical signs and selected
      analytes (total proteins, albumin, globulins and urinary protein:creatinine
      ratio). Concentrations of IgG2 and IgA by TR-IFMA were significantly lower on
      days 30 (p < 0.05) and 180 of treatment (p < 0.0001) compared to day 0 in dogs
      that showed a positive response to treatment. Magnitudes of decrease of IgG2
      (1.66 and 20.4-fold) and IgA (1.3 and 11.43-fold) concentrations on days 30 and
      180 were greater than those of the commercially available ELISA test (1.29 and
      2.06-fold), and that of other analytes (total proteins: 1.11 and 1.25-fold;
      globulins: 1.22 and 1.74-fold; and albumin: 0.93 and 0.8-fold). This study shows
      that serum IgG2 and IgA anti-Leishmania antibodies measured by TR-IFMAs were
      useful for treatment monitoring in dogs with leishmaniosis, showing a significant
      reduction in antibody concentrations earlier than the commercial ELISA assay.
      Results suggest that the method used for antibody measurements greatly influences
      the results and, consequently, the usefulness for measuring anti-Leishmania
      antibodies to monitor the treatment of canine leishmaniosis.

PMID- 29571521
TI  - Outpatient Dermatological Diagnoses in Spain: Results From the National DIADERM
      Random Sampling Project.
AB  - INTRODUCTION: Dermatologists perform most of their work in outpatient or private
      clinics. Data on the diagnoses made by dermatologists in these settings are
      lacking, however, as outpatient activity, unlike hospital activity, is difficult
      to code. The aim of this study was to analyze the diagnoses made by members of
      the Spanish Academy of Dermatology and Venereology (AEDV) at dermatology clinics
      in Spain. METHODOLOGY: We selected a random sample of AEDV dermatologists drawn
      from the AEDV list and stratified by geographic area. The selected dermatologists
      received instructions on how to collect the data required. Each participant
      recorded the diagnosis reached and other data for patients seen during 2
      specified periods: 3 days in January and 3 days in May. The diagnoses were
      subsequently coded by a dermatologist expert in applying the International
      Classification of Diseases (10th revision). In view of the complex nature of the
      sample, data were analyzed with standard error and finite population corrections.
      RESULTS: The sample consisted of 124 dermatologists. Of these, 65% participated
      in the first phase of the study and 59% in the second. An estimated 621 562
      patients (95% CI, 368 130-874 995) visit the dermatologist every month in Spain.
      This is the equivalent of 28 (25-31) patients per day per clinic. The most common
      diagnosis recorded was actinic keratosis, followed by basal cell carcinoma and
      melanocytic nevus. The vast majority of visits took place at the clinic, but 1%
      of patients (0.3%-3%) were assessed using teledermatology. CONCLUSIONS: This is
      the first study in Spain to analyze diagnoses made by AEDV members at outpatient
      dermatology clinics. Our findings show a high volume of activity and will be
      useful for guiding health care planning, resource use, and future studies.

PMID- 29571522
TI  - Inguinal Sentinel Lymph Node Biopsy: Surgical Technique.

PMID- 29571523
TI  - Congenital Aural Atresia prevalence in the Argentinian population.
AB  - INTRODUCTION: Congenital Aural Atresia (CAA) or microtia is a malformation that
      results in esthetic and functional problems. There is little information on
      prevalence, considering that Latin American is the most affected region in the
      world. OBJECTIVE: To determine the prevalence of microtia, considering the
      different ethnical structure of the population. METHODS: A retrospective analysis
      was performed of the clinical reports of newborn infants (public hospitals) in
      three different regions. RESULTS: The incidence of CAA in Argentina was 1 case
      per 7500 new births (i.e. 1.3/10,000). Marked differences were found per
      geographical area. The means were calculated per year by bilateral parametric
      estimation, according to the ethnical origins of the population. In the Caucasoid
      area: 02.47/10,000 (+/-1.2), in the Mestizo area: 03.99/10,000 (+/-0.0) and
      finally in the Amerindian area: 20.93/10,000 (+/-0.1). CONCLUSION: This study
      shows different incidences according to the demographic features of the
      population from 1.90/10,000 to 20.9/10,000. This data indicates that CAA is
      associated with a genetic problem (ethnic differences).

PMID- 29571526
TI  - Peer victimization and suicidal ideation: The role of gender and depression in a
      school-based sample.
AB  - The current study investigated the relations among traditional and cyber
      victimization, depressive symptoms, suicidal ideation, and gender in a school
      based sample of 403 9th grade (13 to 16-year-old) adolescents. Path analyses
      indicated that both traditional victimization and cyber victimization were
      associated with suicidal ideation indirectly through depressive symptoms.
      Although there was little evidence of gender differences in the associations
      among peer victimization and depressive symptoms and suicidal ideation, the
      relation between depressive symptoms and suicidal ideation was found to be
      significantly stronger for girls than boys. The current investigation confirms
      the complexity of the association between peer victimization and suicidal
      ideation and that depressive symptoms, as well as gender, may play a role in this
      complex relation. Future research should continue to explore the associations
      among victimization, depressive symptoms, and suicidal ideation within a social
      ecological framework.

PMID- 29571525
TI  - Possibilities of the three-dimensional virtual environment tridimensional Second
      Life(r) for training in radiology.
AB  - Three-dimensional virtual environments enable very realistic ludic, social,
      cultural, and educational activities to be carried out online. Second Life(r) is
      one of the most well-known virtual environments, in which numerous training
      activities have been developed for healthcare professionals, although none about
      radiology. The aim of this article is to present the technical resources and
      educational activities that Second Life(r) offers for training in radiology based
      on our experience since 2011 with diverse training activities for undergraduate
      and postgraduate students. Second Life(r) is useful for carrying out radiology
      training activities online through remote access in an attractive scenario,
      especially for current generations of students and residents. More than 800
      participants have reported in individual satisfaction surveys that their
      experiences with this approach have been interesting and useful for their
      training in radiology.

PMID- 29571524
TI  - Habits Are Negatively Regulated by Histone Deacetylase 3 in the Dorsal Striatum.
AB  - BACKGROUND: Optimal behavior and decision making result from a balance of control
      between two strategies, one cognitive/goal-directed and one habitual. These
      systems are known to rely on the anatomically distinct dorsomedial and
      dorsolateral striatum, respectively. However, the transcriptional regulatory
      mechanisms required to learn and transition between these strategies are unknown.
      Here we examined the role of one chromatin-based transcriptional regulator,
      histone modification via histone deacetylases (HDACs), in this process. METHODS:
      We combined procedures that diagnose behavioral strategy in rats with
      pharmacological and viral-mediated HDAC manipulations, chromatin
      immunoprecipitation, and messenger RNA quantification. RESULTS: The results
      indicate that dorsal striatal HDAC3 activity constrains habit formation. Systemic
      HDAC inhibition following instrumental (lever press -> reward) conditioning
      increased histone acetylation throughout the dorsal striatum and accelerated
      habitual control of behavior. HDAC3 was removed from the promoters of key
      learning-related genes in the dorsal striatum as habits formed with overtraining
      and with posttraining HDAC inhibition. Decreasing HDAC3 function, either by
      selective pharmacological inhibition or by expression of dominant-negative
      mutated HDAC3, in either the dorsolateral striatum or the dorsomedial striatum
      accelerated habit formation, while HDAC3 overexpression in either region
      prevented habit. CONCLUSIONS: These results challenge the strict dissociation
      between dorsomedial striatum and dorsolateral striatum function in goal-directed
      versus habitual behavioral control and identify dorsostriatal HDAC3 as a critical
      molecular directive of the transition to habit. Because this transition is
      disrupted in many neurodegenerative and psychiatric diseases, these data suggest
      a potential molecular mechanism for the negative behavioral symptoms of these
      conditions and a target for therapeutic intervention.

PMID- 29571527
TI  - Cognitive ability influences on written expression: Evidence for developmental
      and sex-based differences in school-age children.
AB  - Some studies have demonstrated that the Cattell-Horn-Carroll (CHC) cognitive
      abilities influence writing; however, little research has investigated whether
      CHC cognitive abilities influence writing the same way for males and females
      across grades. We used multiple group structural equation models to investigate
      whether CHC cognitive ability influences on written expression differed between
      grades or sex using the Kaufman Assessment Battery for Children, Second Edition
      and the Kaufman Tests of Educational Achievement, Second Edition co-normed
      standardization sample data (N=2117). After testing for consistent measurement of
      cognitive abilities across grades and sex, we tested whether the cognitive
      ability influences on written expression were moderated by grade level or sex. An
      important developmental shift was observed equally across sex groups: Learning
      Efficiency (Gl) influences decreased whereas Crystallized Ability (Gc) influences
      increased after fourth grade. Further, Short-Term Memory (Gsm) and Retrieval
      Fluency (Gr) influences on written expression depended on sex at grades 1-4, with
      larger Gr influences for females and larger Gsm influences for males. We
      internally replicated our main findings using two different cognitive explanatory
      models, adding further support for the developmental and sex-based differential
      cognitive ability influences on writing. Explanatory cognitive models of writing
      need to incorporate development, and possibly, sex to provide an expanded
      understanding of writing development and guard against potential generalizability
      issues characteristic of special population (i.e., male-female) studies.

PMID- 29571528
TI  - Investigating teacher and student effects of the Incredible Years Classroom
      Management Program in early elementary school.
AB  - The present paper reports on the results of a cluster randomized trial of the
      Incredible Years(r) Teacher Classroom Management Program (IY-TCM) and its effects
      on early elementary teachers' management strategies, classroom climate, and
      students' emotion regulation, attention, and academic competence. IY-TCM was
      implemented in 11 rural and semi-rural schools with K-2 teachers and a diverse
      student sample. Outcomes were compared for 45 teachers who participated in five
      full day training workshops and brief classroom consultation and 46 control
      teachers; these 91 teachers had a total of 1192 students. A high level of teacher
      satisfaction was found and specific aspects of the training considered most
      valuable for early elementary teachers were identified. Hierarchical linear
      modeling indicated a statistically significant intervention effect on Positive
      Climate in the classroom (d=0.45) that did not sustain into the next school year.
      No main effects on student outcomes were observed, although a priori moderator
      analyses indicated that students with elevated social-behavioral difficulties
      benefitted with regard to prosocial behavior (d=0.54) and inattention (d=-0.34).
      Results highlight potential benefits and limitations of a universal teacher
      training program for elementary students, and suggest strategies for future
      delivery of the IY-TCM program and areas for future research.

PMID- 29571529
TI  - Teaching in ethnically diverse classrooms: Examining individual differences in
      teacher self-efficacy.
AB  - Using data of 40 native Dutch teachers and their native majority (n=112) and
      ethnic minority students (n=180), this study examined to what extent teachers
      experience differences in self-efficacy in teaching individual majority and
      minority students. We hypothesized that teachers would feel less self-efficacious
      in relation to ethnic minority students and that the difference in self-efficacy
      would be more pronounced when ethnic group differences are more salient (i.e., in
      the context of behavioral problems, ethnically less diverse classrooms, and for
      teachers with high ethnic identification). Our results show that teachers feel
      somewhat less self-efficacious with ethnic minority versus majority students.
      And, the difference in self-efficacy with minority versus majority students was
      more pronounced in relation to internalizing problem behaviors and somewhat more
      distinct in classrooms with relatively few ethnic minority students. The findings
      indicate the importance of a student specific assessment of teacher self-efficacy
      in diverse school contexts.

PMID- 29571530
TI  - Trajectories of teacher-student warmth and conflict at the transition to middle
      school: Effects on academic engagement and achievement.
AB  - Using piece-wise longitudinal trajectory analysis, this study investigated
      trajectories of teacher-reported warmth and conflict in their relationships with
      students 4years prior to and 3years following the transition to middle school in
      a sample of 550 academically at-risk and ethnically diverse adolescents. At the
      transition to middle school, teacher reports of warmth showed a significant drop
      (shift in intercept), above age-related declines. Both warmth and conflict
      declined across the middle school years. Structural equation modeling (SEM)
      tested effects of the shifts in intercept and the post-transition slopes on
      reading and math achievement, teacher-rated engagement, and student-reported
      school belonging 3years post-transition, above pre-transition levels of the
      outcome. For warmth, a drop in intercept predicted lower math scores and
      engagement, and a more positive slope predicted higher engagement. For conflict,
      an increase in intercept and a negative slope predicted lower engagement.
      Implications of findings for reducing normative declines in academic engagement
      in middle school are discussed.

PMID- 29571531
TI  - Harsh parenting and academic achievement in Chinese adolescents: Potential
      mediating roles of effortful control and classroom engagement.
AB  - This study examined (a) the potential mediating roles of effortful control and
      classroom engagement in the association between harsh parenting and adolescent
      academic achievement, and (b) the potential moderating role of gender. Sixth
      through eighth graders in rural China (n=815, mean age=12.55years) reported on
      harsh parenting, effortful control, and classroom engagement. Parents also
      reported on each other's harsh parenting. Academic achievement was assessed by
      students' test scores and teacher-rated academic performance. Results of
      structural equation modeling revealed gender differences in patterns of
      association among the model variables. Harsh parenting was negatively and
      directly associated with academic achievement for both boys and girls. It was
      also negatively and indirectly associated with academic achievement via effortful
      control and classroom engagement sequentially, forming a common indirect "path"
      for boys and girls. The indirect negative effect of harsh parenting on boys'
      academic achievement was mainly realized through the mediator of effortful
      control, whereas this same indirect effect for girls was mainly realized through
      the mediator of classroom engagement. Jointly, effortful control and classroom
      engagement precipitates more indirect effects for boys than for girls in the
      association between harsh parenting and academic achievement. The discussion
      analyzes the potential "paths" from harsh parenting to adolescent academic
      achievement, as well as gender differences in these "paths." The current study
      has implications for teachers and parents eager to improve students' classroom
      engagement and academic achievement.

PMID- 29571532
TI  - Chronic absence, eighth-grade achievement, and high school attainment in the
      Chicago Longitudinal Study.
AB  - Although not as commonly reported as average daily attendance, chronic absence
      data may be of significant importance for understanding student success. Using
      data from 1148 participants in the Chicago Longitudinal Study, we assessed the
      associations of chronic absence in the early middle grades, grades fourth through
      sixth, with eighth-grade achievement and three measures of high school attainment
      including four-year graduation by diploma, graduation by diploma by age 21, and
      any high school completion by age 21. The rate of chronic absenteeism, defined
      here as students missing approximately 14days of school or more in a year, was
      15%. Using Ordinary Least Squares, probit regression, and inverse-probability
      weighting regression-adjustment methods (IPWRA), results indicated that chronic
      absence in the early middle grades was negatively associated (d=-0.17) with
      eighth-grade math achievement and reduced the probability of four-year graduation
      by diploma by 18 percentage points, graduation by diploma by age 21 by 17
      percentage points, and any high school completion by age 21 by 11 percentage
      points. IPWRA yielded similar estimates. Coefficients varied by subgroup with
      males and children of mothers who completed high school experiencing more
      detrimental effects. Associations of chronic absence with outcomes are important
      to understand because school interventions and practices which begin early can be
      effective in reducing the prevalence of absenteeism.

PMID- 29571533
TI  - Comparison of progress monitoring data from general outcome measures and specific
      subskill mastery measures for reading.
AB  - Interventionists often monitor the progress of students receiving supplemental
      interventions with general outcome measures (GOMs) such as curriculum-based
      measurement of reading (CBM-R). However, some researchers have suggested that
      interventionists should collect data more closely related to instructional
      targets, specific subskill mastery measures (SSMMs) because outcomes from GOMs
      such as CBM-R may not be sufficiently sensitive to gauge intervention effects. In
      turn, interventionists may prematurely terminate an effective intervention or
      continue to deliver an ineffective intervention if they do not monitor student
      progress with the appropriate measure. However, such recommendations are based
      upon expert opinion or studies with serious methodological shortcomings. We used
      multi-variate multilevel modeling to compare pre-intervention intercepts and
      intervention slopes between GOM and SSMM data collected concurrently in a sample
      of 96 first, 44 second, and 53 third grade students receiving tier 2 phonics
      interventions. Statistically significant differences were observed between slopes
      from SSMM consonant-vowel-consonant words and CBM-R data. Statistically
      significant differences in slopes were not observed for consonant blend, digraph
      or consonant-vowel-consonant-silent e (CVCe) SSMMs. Results suggest that using
      word lists to monitor student response to instruction for early struggling
      readers is beneficial but as students are exposed to more complex phonetic
      patterns, the distinction between SSMMs and CBM-R become less meaningful.

PMID- 29571534
TI  - Informant similarities, twin studies, and the assessment of externalizing
      behavior: A meta-analysis.
AB  - The purpose of this study was to examine similarity within informant ratings of
      the externalizing behavior of monozygotic (MZ) and dizygotic (DZ) twin pairs. To
      do this, we conducted a meta-analysis of correlations within ratings completed by
      mothers, fathers, teachers, and youth. We retrieved n=204 correlations for MZ
      twins and n=267 correlations for DZ twins from n=54 studies containing n=55
      samples. Results indicated that all four informants were significant negative
      predictors of within-informant correlations in their ratings of MZ, but not DZ
      twins. In the case of longitudinal studies and as the age of MZ twins increased,
      similarity within ratings by mothers was significantly greater than similarity
      within ratings by fathers. Among participant characteristics, we found that (a)
      age was a significant negative predictor of similarity within ratings for MZ
      twins; (b) race was a significant predictor of similarity within ratings for both
      MZ and DZ twins, but in the opposite direction; and (c) DZ opposite sex twins
      were a significant negative predictor of within-rating similarity. Among study
      characteristics for MZ twins, participant group and longitudinal study were
      significant negative predictors of within-rating similarity, and for both MZ and
      DZ twin pairs, non-independence in the data was a significant negative predictor
      of within-rating similarity. For DZ twins, multiple informants were significant
      positive predictors of within-rating similarity, and in longitudinal studies with
      DZ twins, similarity within ratings by mothers was significantly greater than
      similarity within ratings by fathers, and similarity within ratings by fathers
      was significantly less than similarity within ratings by teachers and youth. For
      both MZ and DZ twins, the following study characteristics were significant
      positive predictors of similarity within ratings: study group, number of time
      points, and multiple constructs. All four informants appeared equally skilled at
      predicting within-informant correlations for MZ (but not DZ) twins, with
      participant characteristics having different predictive effects for MZ compared
      to DZ twins, and study characteristics having comparable predictive effects for
      both twin types. Overall, these findings suggest effective discrimination on the
      part of four informants who rated the externalizing behavior of MZ and DZ twins.

PMID- 29571535
TI  - Associations between peer victimization, perceived teacher unfairness, and
      adolescents' adjustment and well-being.
AB  - Negative relationships within the classroom, both with peers and teachers, can be
      very stressful for adolescents and are often found to be associated with a
      variety of negative outcomes. In this study, we investigated the concurrent role
      of peer victimization and perceived teacher unfairness in explaining psychosocial
      problems in a sample of 1378 Italian students (353 middle school students,
      Mage=12.61, SD=0.69, and 1025 high school students, Mage=14.92, SD=0.81).
      Structural equation modeling showed that both peer victimization and perceived
      teacher unfairness were positively associated with reports of more frequent
      psychological and somatic problems, and negatively related to satisfaction with
      friends and sense of safety. Only perceived teacher unfairness showed a
      significant association with satisfaction with school. Results of multi-group
      modeling demonstrated measurement invariance (total scalar invariance) across
      both gender and school-level groups. Some gender and school-level differences in
      the regression coefficients were found. In general, associations between the risk
      factors and adolescents' problems were stronger for girls and for higher school
      students. Findings confirmed that both peer victimization and perceived teacher
      unfairness are significant risk factors within the classroom microsystems.
      Implications for school psychologists are discussed.

PMID- 29571536
TI  - Mentor Support Provisions Scale: Measure dimensionality, measurement invariance,
      and associations with adolescent school functioning.
AB  - Mentoring relationships can have important effects on adolescents' psychosocial
      and academic outcomes; however, the transactions within mentoring relationships
      that may account for impact on psychosocial and academic outcomes are not well
      understood. This study investigated the psychometric properties of the Mentor
      Support Provisions Scale (MSPS), a tool for assessing the types of support that
      mentors provide. Exploratory factor analyses and confirmatory factor analyses
      were used to determine measure dimensionality. Findings indicated acceptable fit
      with a three-factor structure: Academic Support, Intimacy, and Warmth. The MSPS
      was found to have scalar invariance; thus, factor loadings and intercepts are the
      same across student sex and ethnic groups (e.g., White, Hispanic, and Black). In
      structural equation modeling analyses, the three latent factors predicted
      academic engagement and reading and math achievement, above baseline scores.
      Research and practical uses of the MSPS are discussed.

PMID- 29571537
TI  - Improving outgroup attitudes in schools: A meta-analytic review.
AB  - To provide information for educators, educational psychologists, school
      psychologists, and social psychologists, we conducted a quantitative meta
      analytic test of n=50 studies dating from 1995 to 2015 that evaluated the effects
      of in-school interventions on attitudes toward outgroup members (defined as
      members of different ethnic or religious backgrounds or different age groups,
      persons with either physical or mental disabilities, or persons with other
      distinctive features). Overall, the analysis revealed a mean effect size of
      d+=0.36 with a 95% confidence interval that ranged from 0.17 to 0.55, indicating
      significant, moderate intervention effects, supporting the proposition that
      meaningful changes in outgroup attitudes can be obtained by applying anti-bias
      programs in schools. Results from our analysis did not provide evidence that
      teacher-led interventions produce positive outcomes, yet we found that
      interventions delivered by researchers promote positive attitudes toward outgroup
      members. Further, a closer examination demonstrated that one-on-one interventions
      are most effective at tackling intergroup attitudes. However, classroom-wide
      programs are more likely to be introduced into regular school activities because
      of their efficiency and the limited resources available for interventions.

PMID- 29571538
TI  - Efficacy of an exercise intervention among children with comorbid asthma and
      obesity.
AB  - OBJECTIVES: Children with comorbid asthma and obesity present with more severe
      and harder-to-control disease than asthmatic children at healthy weight. Weight
      loss has been shown to improve asthma symptoms, yet physical activity may be
      difficult due to exercise-induced bronchospasm. Children with asthma have lower
      exercise rates than non-asthmatics. The objective of this study was to
      retrospectively evaluate attrition rates and program outcome measures (Body Mass
      Index [BMI] and maximum oxygen consumption [VO2max]) among asthmatic and non
      asthmatic participants. STUDY DESIGN: Clinical data were collected from the
      Healthy Hearts Program, a 12-week nutrition and activity intervention program for
      children who are overweight, obese, or at risk for heart disease and other
      conditions, and used for the study. METHODS: Intervention data and demographics
      were obtained from medical records at the Children's Heart Center Nevada.
      Descriptive statistics, paired t-tests, Cox regression analysis, and analysis of
      covariance were conducted. RESULTS: The mean age of this population (N = 232) was
      11 years; 54% were male, 64% were Hispanic, and 37% had asthma. Median time in
      the program was 9 weeks, and 58% of the population completed the program.
      Unadjusted analyses showed significant BMI decreases in asthmatic (P = 0.002) and
      non-asthmatic (P = 0.001) participants and increases in cardiorespiratory
      function for asthmatic males and females (P = 0.003, P = 0.004) and non-asthmatic
      males and females (P < 0.001 for both). Asthmatic and non-asthmatic children both
      had improved exercise intensity (P = 0.033, P < 0.001). CONCLUSIONS: This program
      is both beneficial and practical for obese children with asthma for losing weight
      and improving cardiorespiratory function.

PMID- 29571539
TI  - Re: 'History in health: health promotion's underexplored tool for change'.

PMID- 29571540
TI  - What is the prevalence of cognitive impairment in lupus and which instruments are
      used to measure it? A systematic review and meta-analysis.
AB  - OBJECTIVES: To systematically review the literature on the prevalence of
      Cognitive Dysfunction (CD) in SLE patients in studies that used a specified
      neuropsychological instrument. METHODS: This review was prepared with a protocol
      following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis
      Protocols statement. Literature search in Ovid Medline, Embase, and Psyc INFO for
      articles on CD in adult SLE patients was conducted. Included studies were
      critically appraised (Newcastle-Ottawa Evaluation Scale) and the Pooled
      Prevalence (PP) of CD was studied for all instruments. The association between
      demographics and CD, the risk of CD in SLE compared to healthy subjects and
      patients with RA, and the course of CD over time were studied narratively
      whenever sufficient information was available. RESULT: Of 8054 references, 670
      were selected for detailed review and 78 were included in the final analysis.
      Comprehensive Battery (CB) was utilized in 35 studies in 2463 SLE patients and PP
      was 38% (95%; CI: 33-43%). The CD prevalence was higher in NPSLE [PP 39% (95% CI:
      24-55%]. Automated Neuropsychological Assessment Metric (ANAM) was utilized in 7
      studies in 438 patients (PP of CD 26% (95% CI: 12-42%). Other less frequently
      utilized tools were the Modified Mini-Mental State Exam (MMSE), Montreal
      Cognitive Assessment (MoCA), Controlled Oral Word Association Test (COWAT) and
      The Hopkins Verbal Learning Test-Revised (HVLT-R) and subjective tools and
      others. The relative risk for CD in SLE was greater when compared to RA and to
      healthy individuals; RR being 1.80 and 2.80, respectively. Information on
      demographics and its association with CD was very heterogeneous among studies.
      CONCLUSION: Patients with lupus have a high prevalence of CD. The delay in
      diagnosis of CD is complex; although caregivers and patients express concerns
      about cognitive function, testing for CD often imposes administrative and cost
      burdens. There is an unmet need to identify the best screening, diagnostic
      metrics of CD. The assessment of cognitive function over time, and the
      association of demographics with CD, will require further research.

PMID- 29571541
TI  - New concept to describe three-phase capillary pressure-degree of saturation
      relationship in porous media.
AB  - The Leverett concept is used conventionally to model the relationship between the
      capillary pressures and the degrees of saturation in the water-nonaqueous phase
      liquid (NAPL)-air three-phase system in porous media. In this paper, the
      limitation of the Leverett concept that the concept is not applicable in the case
      of nonspreading NAPLs is discussed through microscopic consideration. A new
      concept that can be applied in the case of nonspreading NAPLs as well as
      spreading NAPLs is then proposed. The validity of the proposed concept is
      confirmed by comparing with past experimental data and simulation results
      obtained using the conventional model based on the Leverett concept. It is
      confirmed that the proposed concept can correctly predict the observed
      distributions of NAPLs, including those of nonspreading ones.

PMID- 29571542
TI  - The Multidisciplinary Approach to Pediatric Aerodigestive Disorders.
AB  - Multidisciplinary programs for the care of children with upper and lower
      respiratory and gastrointestinal tract disorders have emerged across the United
      States and become known as aerodigestive centers. This model is designed to
      improve clinical outcomes and healthcare value through a coordinated approach by
      a team that appreciates the inter-relatedness of these disorders. The primary
      elements include: (1) Interdisciplinary medical and surgical team, (2) Care
      coordination, (3) Team meeting, and (4) Combined endoscopic procedures. This
      article will describe the origin and current trends in the multidisciplinary
      approach to pediatric aerodigestive disorders.

PMID- 29571543
TI  - Dysphagia in Children.
AB  - Speech-Language Pathologists (SLP) play an integral role in evaluating and
      treating pediatric patients with dysphagia related to aerodigestive disorders.
      Non-supportive anatomy, cardio-respiratory and medical status, state control,
      neurologic functioning, postural stability and control, gastrointestinal
      functioning, hunger and satiation, developmental abilities, oral-motor skills,
      oral/pharyngeal reflexes, airway protection and secretion management can create
      barriers to successful oral feeding. Swallowing is broken down into four phases
      and difficulties can occur during any phase or in combination with another phase
      of swallowing. Dysphagia is diagnosed by both clinical and instrumental
      evaluation. Objective evaluations of swallowing include the Video Fluoroscopic
      Swallow Study (VFSS) and Fiberoptic Endoscopic Evaluation of Swallowing (FEES). A
      Video Fluoroscopic Swallow Study (VFSS) is a radiographic study assessing
      oropharyngeal swallow function. The Fiberoptic Endoscopic Evaluation of
      Swallowing (FEES) is conducted by passing a laryngoscope through the nose to just
      below the soft palate for a "bird's eye view" of laryngeal anatomy and swallow
      function. Following a diagnosis of dysphagia from either a clinical or
      instrumental assessment, there are a variety of avenues that can be pursued
      including diet modifications, compensatory strategies, and use of specialized
      equipment to ensure a safe feeding plan and reduce the risk of aspiration. In
      conclusion, through numerous evaluation and intervention approaches, the
      contributions of SLPs helps provide input for well-rounded, multi-disciplinary
      plans supporting successful oral feeding.

PMID- 29571544
TI  - Chronic Pulmonary Aspiration in Children: Diagnosis and Management.
AB  - Chronic pulmonary aspiration (CPA) is a common cause of morbidity in children
      with complex aerodigestive disorders. CPA can be caused by swallowing
      dysfunction, anatomic, or dynamic abnormalities of the airways, and/or other
      circumstances that overcome the child's natural capacity to protect the airway.
      Diagnostic evaluation for suspected aspiration aims to characterize the
      swallowing function, identify the etiology of aspiration, including anatomic
      and/or dynamic abnormalities causing aspiration, and evaluate for the development
      of aspiration sequelae (e.g., bronchiectasis). CPA management approach should be
      guided by the recognized risk factors and co-morbidities, and directed to
      decrease the events of aspiration, improve clearance of aspirated material, and
      limit the development of aspiration sequelae (e.g., chronic inflammation and
      recurrent infections). This article presents a practical approach for the
      diagnosis and management of chronic pulmonary aspiration (CPA) in children.

PMID- 29571545
TI  - Diagnosis and Management of Laryngotracheoesophageal Cleft.
AB  - Laryngotracheoesophageal cleft (LTEC) is a rare anatomic cause of aspiration in
      the newborn and infant. The clinical presentation of infants with LTEC is
      variable and will usually vary with the degree of anatomic communication between
      the airway and esophagus. The diagnosis of LTEC is often challenging,
      particularly in cases where the presentation and pathology are more subtle.
      Management of LTEC depends upon the clinical presentation, degree of aspiration,
      and anatomic depth of the cleft. The goal of this review is to present the
      clinician with a practical approach to diagnosis and management of this rare but
      challenging congenital airway anomaly.

PMID- 29571546
TI  - Gastroesophageal Reflux Disease and Aerodigestive Disorders.
AB  - This relationship between gastroesophageal reflux and airway disorders is
      complex, possibly bidirectional, and not clearly defined. The tools used to
      investigate gastroesophageal reflux are mostly informative about involvement of
      gastroesophageal reflux within the gastrointestinal tract, although they are
      often utilized to study the relationship between gastroesophageal reflux and
      airway issues with are suspected to occur in relation to reflux. These modalities
      often lack specificity for reflux-related airway disorders. Co-incidence of
      gastroesophageal reflux and airway disorders does not necessarily infer
      causality. While much of our focus has been on managing acidity, controlling
      refluxate is an area that has not been traditionally aggressively pursued. Our
      management approach is based on some of the evidence presented, but also often
      from a lack of adequate study to provide further guidance.

PMID- 29571547
TI  - Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the
      esophagus that effects children and adults. Typical symptoms of EoE typically
      involve failure to thrive and vomiting in small children, and dysphagia and food
      impaction in adolescents and adults. However, throat clearing, choking, gagging,
      and hoarseness have also been observed and these issues often bring patients to
      first seek otolaryngology and pulmonary evaluation. Diagnosis is only made by
      esophogastroduodenoscopy with biopsy, so clinicians must have a low threshold for
      considering eosinophilic esophagitis even in the absence of frank
      gastrointestinal symptoms.

PMID- 29571549
TI  - Letter from the Editor: Abdominal Imaging.

PMID- 29571548
TI  - Analysis of chemosensory function in patients with chronic Eustachian tube
      dysfunction prior to and after balloon dilatation.
AB  - OBJECTIVE: Eustachian tube dysfunction (ETD) affects approximately 1% of adults
      in the general population. Non treated Eustachian tube dysfunction can result in
      chronic middle ear diseases, which have been shown to significantly affect taste
      sensitivity. A promising treatment is balloon dilatation of the Eustachian tube.
      The primary aim of the present study was to investigate whether individuals with
      ETD had impairment in chemosensory functions, and the changes of the chemosensory
      function after balloon dilatation of the Eustachian tube. METHODS: 26 patients
      (17 female, 9 male) (=56 ears) suffering from ETD with a mean age of 39+/-15years
      were included in the present study. 20 patients (76%) returned to be evaluated at
      the follow up (=40 ears) 51+/-22days after balloon dilatation. For pre- and post
      operation, gustatory function was measured with a lateralized gustatory test with
      the taste strips and olfactory function was tested by means of the Sniffin'
      Sticks test battery (threshold, discrimination and identification (ID)). RESULTS:
      Patients' baseline taste function (summed taste score 9.8+/-3.5 (mean+/-SD)) was
      significantly impaired compared to normative data (summed taste score 12.4+/-2.3;
      p=0.002). After balloon dilatation of the Eustachian tube, the taste function
      remained stable (summed taste score 9.4+/-4.3; p=0.814). Olfactory function (odor
      ID, summed score (TDI)) improved postoperatively (TDI 32.4+/-3.6) compared to pre
      operative scores (TDI 33.6+/-4.0; p=0.012), but not to a clinically relevant
      extent. CONCLUSION: This study suggests, that patients suffering from ETD exhibit
      reduced taste scores. Balloon dilatation of the Eustachian tube does not seem to
      influence gustatory function, but olfactory function showed improvement.

PMID- 29571550
TI  - CT Imaging of Emergent Renal Conditions.
AB  - The kidneys are paired intra-abdominal organs which provide essential functions
      and maintain homeostasis throughout the human body. Numerous disease processes
      affect the kidneys and cause acute renal dysfunction or other potentially
      catastrophic complications. These conditions can be broadly categorized into
      obstructive, infectious, hemorrhagic, traumatic, and vascular diseases. Imaging
      plays a vital role in the work-up and diagnosis of acute and emergent renal
      conditions. Evaluation of emergent renal conditions with a focus on CT imaging is
      discussed.

PMID- 29571551
TI  - Computed Tomography of Internal Hernias Following Laparoscopic Roux-en-Y Gastric
      Bypass Surgery.
AB  - Internal hernia in the postoperative laparoscopic Roux-en-Y patient is a
      diagnosis associated with significant morbidity and risk of death. The
      radiologist plays an instrumental role in workup of this patient group; however,
      the imaging assessment of these patients is not straightforward given their
      complex postsurgical anatomy. Multiple radiologic signs of internal hernia have
      been studied in the literature. This review article presents these signs with
      representative cases as well as a summary of their diagnostic accuracy.

PMID- 29571552
TI  - Imaging of Oncologic Emergencies.
AB  - Oncologic emergencies can be either the result of the primary tumor, its
      metastasis, a paraneoplastic syndrome or reaction to the chemotherapy. Imaging
      plays a crucial role in ensuring a prompt diagnosis as well as assisting in the
      therapeutic management. In this article, we discuss the common thoracic and
      abdominal oncological emergencies that may be encountered in an emergency
      department.

PMID- 29571553
TI  - Pneumatosis From Esophagus to Rectum: A Comprehensive Review Focusing on Clinico
      Radiological Differentiation Between Benign and Life-Threatening Causes.
AB  - Pneumatosis of the alimentary tract may occur from the esophagus to rectum as a
      result of a wide spectrum of conditions that range from benign to life
      threatening. Although distinguishing between these 2 groups is of paramount
      importance for an appropriate clinical management, it still remains a challenge
      for the radiologist in the daily practice. In the light of the current
      literature, we provide in the present article a comprehensive review focusing on
      the clinical, laboratory, and radiological findings that most consistently may
      allow such a differentiation. We also provide a pictorial essay illustrating this
      range of diagnoses, briefly discussing each one.

PMID- 29571554
TI  - Imaging Manifestations of Peptic Ulcer Disease on Computed Tomography.
AB  - Although the overall prevalence of peptic ulcer disease (PUD) has decreased in
      modern times, its actual incidence may be underestimated owing to the nonspecific
      clinical presentations patients' manifest. The potential lethal complications
      that can result from PUD include life-threatening abdominal hemorrhage and bowel
      perforation that result in significant morbidity and mortality. Computed
      tomography (CT) imaging historically lacks specificity in detecting PUD-related
      pathology in the stomach and proximal small bowel segments. Therefore, these are
      potential pitfalls in the radiologist's search pattern on abdominopelvic CT
      imaging. This article highlights imaging features of uncomplicated PUD on CT
      imaging in order to allow for early detection of this disease process on imaging
      and the prevention of potential high-grade complications by recommending
      esophagogastroduodenoscopy.

PMID- 29571555
TI  - Diffuse Liver Diseases: Role of imaging.
AB  - Nowadays, the most common imaging techniques allow to study focal liver lesions
      with high diagnostic accuracy but a relatively recent emerging field of interest
      is represented by diffuse liver disease. They include a variegated series of
      storage and metabolic pathologies (ie, iron overload disorders and steatosis)
      requiring a precise diagnosis not always possible at imaging due to the
      overlapping of findings at conventional ultrasound, CT, or MR studies. In recent
      years, several imaging tecniques and specific softwares have been developed,
      especially for ultrasound and MR imaging, in order to identify different
      parameters useful in the noninvasive recognition and follow-up of these diffuse
      processes involving the liver. The aim of this article is to describe the most
      common and useful imaging findings of the most common and uncommon diffuse liver
      diseases illustrating the newest imaging technologies and developments at our
      disposal with corresponding advantages, limitations, and pitfalls.

PMID- 29571556
TI  - Common and Uncommon Benign Pancreatic Lesions Mimicking Malignancy: Imaging
      Update and Review.
AB  - There is a broad range of inflammatory, pseudotumoral, and benign lesions that
      may masquerade as pancreatic malignancies, often representing a challenge to the
      radiologist. Unawareness of these entities can lead to inadequate differential
      diagnoses or misdiagnosis, with important prognostic and therapeutic
      consequences. The purpose of this article is to revisit a spectrum of lesions,
      varying from common to exceedingly rare nonmalignant, that may mimic malignant
      pancreatic neoplasms on imaging, identifying relevant features that may
      contribute to reaching the correct diagnosis. Representative cases include focal
      fatty replacement, intrapancreatic accessory spleen, pancreatic lobulation,
      lipoma, autoimmune pancreatitis, focal pancreatitis, eosinophilic pancreatitis,
      groove pancreatitis, hemangioma, intrapancreatic aneurysm, tuberculosis, and
      Castleman's disease.

PMID- 29571557
TI  - Computed Tomography and Magnetic Resonance Imaging Findings of Inflammatory
      Pseudotumors in the Abdomen and Pelvis: Current Concepts and Pictorial Review.
AB  - The group of inflammatory pseudotumors (IPTs) encompasses a variety of rare
      neoplastic and nonneoplastic entities described to occur in almost every location
      in the body and whose clinical features and aggressive imaging findings (varying
      from infiltrative to mass-forming lesions), frequently mimic those of malignant
      tumors. The radiologic features of IPTs are variable and nonspecific, the imaging
      findings depending on the body location and involved organ. Abdominopelvic IPTs
      are rare and the purposes of this review, therefore, are to familiarize the
      radiologist with the wide spectrum of computed tomography and magnetic resonance
      imaging findings of IPTs in various locations throughout the abdomen and pelvis,
      discussing the imaging features that allow consideration of IPTs in the
      differential diagnosis of soft-tissue masses within the pertinent clinical
      setting. Radiologists should be aware of this group of entities, as a
      preoperative histopathologic diagnosis upon radiological suspicion may help to
      differentiate IPTs from malignancy and to allow the most appropriate clinical
      work-up for these patients.

PMID- 29571558
TI  - Abdominal Wall Masses: CT Findings and Clues to Differential Diagnosis.
AB  - The abdominal wall does not comprise a distinct organ, and is often cursorily
      evaluated on CT. However, it is affected by many different pathological
      processes. These may be categorized according to their underlying etiology
      trauma, infection or inflammation, iatrogenic and neoplastic process-or according
      to the abdominal wall layer they affect. We chose instead to group these lesions
      into 6 distinct categories based on their CT characteristic density: solid,
      infiltrative, hypervascular, fluid, fat, and bone density lesions. We highlight
      throughout the article the importance of integrating pertinent clinical history
      to narrow the differential diagnosis.

PMID- 29571559
TI  - Otolaryngology in Low-Resource Settings: Practical and Ethical Considerations.
AB  - Providing otolaryngology care in low-resource settings requires careful
      preparation to ensure good outcomes. The level of care that can be provided is
      dictated by available resources and the supplementary equipment, supplies, and
      personnel brought in. Other challenges include personal health and safety risks
      as well as cultural and language differences. Studying outcomes will inform
      future missions. Educating and developing ongoing partnerships with local
      physicians can lead to sustained improvements in the local health care system.

PMID- 29571560
TI  - Otolaryngology Around the World.

PMID- 29571561
TI  - Absence of neurovascular conflict during microvascular decompression while
      treating essential trigeminal neuralgia. How to proceed? Systematic review of
      literature.
AB  - INTRODUCTION: Neurovascular conflict is the most accepted hypothesis for the
      cause for trigeminal neuralgia. Microvascular decompression of the trigeminal
      nerve is the most common surgical treatment for these patients. However, despite
      advances in diagnostic techniques, neurovascular conflict is sometimes not
      detected during surgery. The aim of this paper is to systematically review all
      the options available to best manage this scenario. RESULTS: Several techniques
      that could be used during microvascular decompression for trigeminal neuralgia in
      the absence of neurovascular conflict have been described. The success rates of
      these techniques, pain recurrence rates and rates of complications are also
      reported. Finally, we provide suggestions based on our experience. CONCLUSIONS:
      There is no gold standard, but several techniques could be successfully used in
      the absence of neurovascular conflict. The use of destructive techniques, such as
      PSR, should be held as treatments of last resort.

PMID- 29571562
TI  - [A Massive Open Oneline Course (MOOC) on pratical histology: A goal, a tool, a
      large public ! Return on a first experience].
AB  - A goal ! The MOOC entitled "Introduction to Histology, A Human Tissue
      Exploration" correspond to our vision of the practice of General Histology, which
      is based on the ability to diagnose 5 families of biological tissues. Ultimately,
      participants must be able to recognize the different types of cells and all the
      surrounding elements in order to understand how they organize themselves to form
      tissues with specific functions. A tool ! This know-how is based on reasoning
      from observations of microscopic structures. Learners are therefore invited to
      manipulate a virtual microscope to explore biological samples on histological
      slides digitized. Annotations, comments, drawings or photos are associated with
      landmarks that enrich the study of these histological sections. A target audience
      ! Two educational paths allow deepening the subject in a different way and thus
      matching the goals or motivations of each one. After a first year of experience,
      usage statistics and surveys of our learners show that the MOOC Histo has allowed
      each of them to find an interest and federate a community of motivated learners.

PMID- 29571563
TI  - [PD-L1 testing in non-small cell lung carcinoma: Guidelines from the PATTERN
      group of thoracic pathologists].
AB  - Lung cancer is the leading cause of cancer death in France with low response
      rates to conventional chemotherapy. Nevertheless, new therapies have emerged
      recently, among which PD1 immune checkpoint inhibitors (ICI), such as nivolumab
      (OPDIVO(r), Bristol-Myers Squibb) and pembrolizumab (KEYTRUDA(r), Merck & Co), or
      PD-L1 ICI, such as atezolizumab (TECENTRIQ(r), Genentech), durvalumab
      (IMFINZI(r), Astra-Zeneca), and avelumab (BAVENCIO(r), EMD Serono). The
      prescription of pembrolizumab for advanced stage non-small cell lung carcinoma
      (NSCLC) patients requires the demonstration of PD-L1 expression by tumor cells by
      immunohistochemistry (IHC) (minimum of 50% of positive tumor cells is required
      for first-line setting, and of 1% for second-line and beyond) and PD-L1 assay is
      now considered as a companion diagnostic tool for this drug. Numerous
      standardized PD-L1 assays performed on dedicated platforms have been validated in
      clinical trials, each antibody being associated to one specific PD1 or PD-L1
      inhibitor. However, not all pathologists have access to the dedicated platforms
      and the high cost of these assays is still a limitation to their implementation;
      in addition, the small size of the NSCLC tumor samples does not allow to perform
      at the same time multiple assays for multiple drugs. The use of laboratory
      developed tests seems feasible but their validation must guarantee the same
      sensitivities and specificities as standardized tests. In this context, the
      French group of thoracic pathologists PATTERN has teamed up with thoracic
      oncologists to provide recommendations on the indication, the critical technical
      steps and the interpretation of the PD-L1 IHC test to help pathologists to
      implement quickly and in the best conditions this new theranostic test.

PMID- 29571564
TI  - Balance and lower limb loads distribution after Ilizarov corticotomy.
AB  - INTRODUCTION: Normal balance and symmetric distribution of lower limb loads are
      associated with adequate muscle strength, joint mobility and proprioception. The
      aim of this study was to analyze the distribution of lower limb loads and balance
      prior to and after axis correction and lengthening with Ilizarov method.
      MATERIALS AND METHODS: The prospective analysis included 20 patients from our
      clinic, who have been subjected to distraction-corrective lower limb
      corticotomies with the Ilizarov method in 2014-2015. Balance and distribution of
      lower limb loads were determined with a pedobarographic platform. RESULTS: Prior
      to the surgery, mean loads on affected and non-affected limbs corresponded
      to42%and58%of body weight, respectively. Mean loads on affected and non-affected
      limbs during the postoperative examination did not differ significantly. Mean
      path length of the center of gravity prior to and after the surgery amounted
      to143.27 cm and 125.11 cm, respectively. Mean area of the center of gravity was
      7.81 cm2prior to the surgery and 5.81 cm2after the procedure. DISCUSSION: Our
      present study showed that distraction-corrective Ilizarov corticotomy may provide
      more symmetric distribution of lower limb loads and improvement of balance. This
      outcome should be considered satisfactory from the perspective of the locomotor
      system statics. Corticotomies with Ilizarov method provide symmetric distribution
      of loads between non-affected and operated limb.

PMID- 29571566
TI  - High intake of orange juice and cola differently affects metabolic risk in
      healthy subjects.
AB  - BACKGROUND: Higher consumption of sugar-containing beverages has been associated
      with an elevated risk of type 2 diabetes and gout. Whether this equally applies
      to cola with an unhealthy image and orange juice (OJ) having a healthy image
      remains unknown. METHODS: In order to investigate whether OJ and cola differently
      affect metabolic risk 26 healthy adults (24.7 +/- 3.2 y; BMI 23.2 +/- 3.3 kg/m2)
      participated in a 2 * 2-wk intervention and consumed either OJ or caffeine-free
      cola (20% Ereq as sugar from beverages) in-between 3 meals/d at ad libitum energy
      intake. Glycemic control, uric acid metabolism and gut microbiota were assessed
      as outcome parameters. RESULTS: Fecal microbiota, body weight, basal and OGTT
      derived insulin sensitivity remained unchanged in both intervention periods.
      Levels of uric acid were normal at baseline and did not change with 2-wk cola
      consumption (-0.03 +/- 0.67 mg/dL; p > 0.05), whereas they decreased with OJ
      intervention (-0.43 +/- 0.56 mg/dL; p < 0.01) due to increased uric acid
      excretion (+130.2 +/- 130.0 mg/d; p < 0.001). Compared to OJ, consumption of cola
      led to a higher daylong glycemia (DeltaiAUC: 36.9 +/- 83.2; p < 0.05), an
      increase in glucose variability (DeltaMAGE-Index: 0.29 +/- 0.44; p < 0.05), and a
      lower 24 h-insulin secretion (DeltaC-peptide excretion: -31.76 +/- 38.61 MUg/d; p
      < 0.001), which may be explained by a decrease in serum potassium levels (-0.11
      +/- 0.24 mmol/L; p < 0.05). CONCLUSION: Despite its sugar content, regular
      consumption of large amounts of OJ do not increase the risk of gout but may even
      contribute to lower uric acid levels. The etiology of impaired insulin secretion
      with cola consumption needs to be further investigated.

PMID- 29571565
TI  - Heritability of the timing of food intake.
AB  - BACKGROUND & AIMS: While environmental factors are presumed to be primary drivers
      of food timing, preliminary evidence suggests that genetics may be an additional
      determinant. The aim was to explore the relative contribution of genetics and
      environmental factors to variation in the timing of food intake in a Spanish twin
      population. Because chronotype, bedtime and wake time are related to food timing,
      covariance with food timing was further assessed. METHODS: In this observational
      study, 53 pairs of adult (mean (SD) = 52 (6.03) years) female twins (28
      monozygotic; 25 dizygotic) were recruited from the Murcia Twin Register. Zygosity
      was determined by DNA-testing. Timing of the three main meals of the day was
      assessed via 7-day dietary records, and the midpoint of food intake was computed
      by calculating the midpoint between breakfast and dinner times. Chronotype,
      bedtime and wake time were self-reported. Heritability of food timing and related
      traits were estimated by comparing monozygotic and dizygotic twin correlations
      and fitting genetic structural equation models to measured variables. RESULTS: We
      observed genetic influences for food timing, with highest heritability for the
      midpoint of food intake (64%) in an overweight/obese population (BMI = 26.01 +/-
      3.77). Genetic factors contributed to a higher degree to the timing of breakfast
      (56%) than the timing of lunch (38%) or dinner (n.s.). Similarly, heritability
      estimates were larger in related behavioral traits earlier on in the day (i.e.
      wake time, (55%)), than those later on in the day (i.e. bedtime, (38%)).
      Bivariate analyses revealed a significant genetic overlap between food timing and
      bedtime and chronotype (rG between 0.78 and 0.91). CONCLUSIONS: Genetic
      influences appear to account for a significant proportion of the variability in
      food timing, particularly breakfast. Thus, interventions related to food timing
      may be more effective when targeting afternoon/evening traits, such as lunch or
      dinner times. Furthermore, our data suggest shared genetic architecture
      underlying food timing and phenotypically related traits. CLINICAL TRIAL:
      NCT03059576. https://clinicaltrials.gov/ct2/show/NCT03059576.

PMID- 29571567
TI  - Palliative Care for People With Hepatocellular Carcinoma, and Specific Benefits
      for Older Adults.
AB  - PURPOSE: Hepatocellular carcinoma (HCC), the most common type of primary liver
      cancer, has a rapidly rising prevalence in the United States and a very poor
      overall rate of survival. This epidemic is driven by the cohort of aging Baby
      Boomers with hepatitis C viral infection and the increasing prevalence of
      cirrhosis as a result of nonalcoholic steatohepatitis. Because curative options
      are limited, the disease course creates, in patients and their families,
      distressing uncertainty around prognosis and treatment decisions. Older adults
      are disproportionately affected by HCC and have more comorbidities, adding to the
      complexity of the disease. This population would benefit from increased access to
      palliative care services, which can potentially complement the treatments
      throughout the disease trajectory. The purpose of this review was to use existing
      evidence to propose a new model of palliative care integration in patients with
      HCC. Thus, we focus on the HCC stage and the treatment algorithm, the ways that
      palliative care can offer support in this population at each stage, as well as
      elements that can enhance patient and family support throughout the entire
      disease trajectory, with an emphasis on the care of older adults with HCC.
      METHODS: This is a narrative review in which we identify evidence-based ways that
      palliative care can help younger and older adults with HCC and their families, at
      each stage of HCC and throughout the disease trajectory. FINDINGS: We propose
      ways to integrate HCC and palliative care based on the existing evidence in both
      fields. Palliative care offers support in symptom management, advanced care
      planning, and decision making in ways that are specific to each stage of HCC. We
      also discuss the evidence that illustrates the palliative care needs of patients
      with HCC that span the entire course of illness, including coping with the
      stigmatization of liver disease, addressing informational needs at different
      stages, and discussing quality of life longitudinally. IMPLICATIONS: Integrating
      palliative care into the treatment of patients with HCC has the potential to
      improve outcomes, although more research is needed to build this evidence base.

PMID- 29571568
TI  - Copper (II) addition to accelerate lactic acid production from co-fermentation of
      food waste and waste activated sludge: Understanding of the corresponding
      metabolisms, microbial community and predictive functional profiling.
AB  - Bio-refinery of food waste and waste activated sludge to high value-added
      chemicals, such as lactic acid, has attracted particular interest in recent
      years. In this paper, the effect of copper (II) dosing to the organic waste
      fermentation system on lactic acid production was evaluated, which proved to be a
      promising method to stimulate high yield of lactic acid (77.0% higher than blank)
      at dosage of 15 MUM-Cu2+/g VSS. As mechanism study suggested, copper addition
      enhanced the activity of alpha-glycosidase and glycolysis, which increased the
      substrate for subsequent acidification; whereas, the high dosage (70 MUM-Cu2+/g
      VSS) inhibited the conversion of lactic acid to VFA, thus stabilized lactic acid
      concentration. Microbial community study revealed that small amount of copper
      (II) at 15 MUM/g VSS resulted in the proliferation of Lactobacillus to 82.6%,
      which mainly produced lactic acid. Finally, the variation of functional
      capabilities implied that the proposed homeostatic system II was activated at
      relatively low concentration of copper. Meanwhile, membrane transport function
      and carbohydrate metabolism were also strengthened. This study provides insights
      into the effect of copper (II) on the enhancement of lactic acid production from
      co-fermentation of food waste and waste activated sludge.

PMID- 29571569
TI  - Life cycle assessment of integrated solid state anaerobic digestion and
      composting for on-farm organic residues treatment.
AB  - Driven by the gradual changes in the structure of energy consumption and
      improvements of living standards in China, the volume of on-farm organic solid
      waste is increasing. If untreated, these unutilized on-farm organic solid wastes
      can cause environmental problems. This paper presents the results of a life cycle
      assessment to compare the environmental impacts of different on-farm organic
      waste (which includes dairy manure, corn stover and tomato residue) treatment
      strategies, including anaerobic digestion (AD), composting, and AD followed by
      composting. The input life cycle inventory data are specific to China. The
      potential environmental impacts of different waste management strategies were
      assessed based on their acidification potential (AP), eutrophication potential
      (EP), global warming potential (GWP), ecotoxicity potential (ETP), and resource
      depletion (RD). The results show that the preferred treatment strategy for dairy
      manure is the one that integrated corn stover and tomato residue utilization and
      solid state AD technologies into the system. The GWP of integrated solid state AD
      and composting was the least, which is -2900 kg CO2 eq/ t of dairy manure and
      approximately 14.8 times less than that of current status (i.e., liquid AD of
      dairy manure). Solid state AD of dairy manure, corn stover and tomato residues is
      the most favorable option in terms of AP, EP and ETP, which are more than 40%
      lower than that of the current status (i.e., AP: 3.11 kg SO2, EP: -0.94 kg N, and
      ETP: -881 CTUe (Comparative Toxic Units ecotoxicity)). The results also show that
      there is a significant potential for AP, EP, ETP, and GWP reduction, if AD is
      used prior to composting. The scenario analysis for transportation distance
      showed that locating the AD plant and composting facility on the farm was
      advantageous in terms of all the life cycle impact categories.

PMID- 29571570
TI  - Inside the small-scale composting of kitchen and garden wastes: Thermal
      performance and stratification effect in vertical compost bins.
AB  - Decentralized composting has been proposed as a best available practice, with a
      highly positive impact on municipal solid wastes management plans. However, in
      cold climates, decentralized small-scale composting performance to reach
      thermophilic temperatures (required for the product sanitization) could be poor,
      due to a lack of critical mass to retain heat. In addition, in these systems the
      composting process is usually disturbed when new portions of fresh organic waste
      are combined with previous batches. This causes modifications in the well-known
      composting evolution pattern. The objective of this work was to improve the
      understanding of these technical aspects through a real-scale decentralized
      composting experience carried out under cold climate conditions, in order to
      assess sanitization performance and to study the effects of fresh feedstock
      additions in the process evolution. Kitchen and garden organic wastes were
      composted in 500 L-static compost bins (without turning) for 244 days under cold
      climate conditions (Bariloche, NW Patagonia, Argentina), using pine wood shavings
      in a ratio of 1.5:1 v: v (waste: bulking agent). Temperature profile, stability
      indicators (microbial activity, carbon and nitrogen contents and ratio) and other
      variables (pH and electrical conductivity), were monitored throughout the
      experience. Our results indicate that small-scale composting (average generation
      rate of 7 kg d-1) is viable under cold weather conditions, since thermophilic
      sanitization temperatures (> 55  degrees C) were maintained for 3 consecutive
      days in most of the composting mass, according to available USEPA regulations
      commonly used as a reference for pathogens control in sewage sludge. On the other
      hand, stability indicators showed a differentiated organic matter degradation
      process along the compost bins height. Particularly, in the bottommost composting
      mix layer the process took a longer period to achieve compost stability than the
      upper layers, suggesting that differential organic matter transformation appears
      not to be necessarily associated to the order of the waste batches incorporation
      in a time line, as it could be expected. These findings suggest the need to
      discuss new ways of studying the composting process in small-scale compost bins
      as well as their commercial design.

PMID- 29571571
TI  - Disulfiram-based disulfides as narrow-spectrum antibacterial agents.
AB  - Sixteen disulfides derived from disulfiram (AntabuseTM) were evaluated as
      antibacterial agents. Derivatives with hydrocarbon chains of seven and eight
      carbons in length exhibited antibacterial activity against Gram-positive
      Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Listeria spp. A
      comparison of the cytotoxicity and microsomal stability with disulfiram further
      revealed that the eight carbon chain analog was of lower toxicity to human
      hepatocytes and has a longer metabolic half-life. In the final analysis, this
      investigation concluded that the S-octylthio derivative is a more effective
      growth inhibitor of Gram-positive bacteria than disulfiram and exhibits more
      favorable cytotoxic and metabolic parameters over disulfiram.

PMID- 29571572
TI  - Design, synthesis, and evaluation of l-cystine diamides as l-cystine
      crystallization inhibitors for cystinuria.
AB  - To overcome the chemical and metabolic stability issues of l-cystine dimethyl
      ester (CDME) and l-cystine methyl ester (CME), a series of l-cystine diamides
      with or without Nalpha-methylation was designed, synthesized, and evaluated for
      their inhibitory activity of l-cystine crystallization. l-Cystine diamides 2a-i
      without Nalpha-methylation were found to be potent inhibitors of l-cystine
      crystallization while Nalpha-methylation of l-cystine diamides resulted in
      derivatives 3b-i devoid of any inhibitory activity of l-cystine crystallization.
      Computational modeling indicates that Nalpha-methylation leads to significant
      decrease in binding of the l-cystine diamides to l-cystine crystal surface. Among
      the l-cystine diamides 2a-i, l-cystine bismorpholide (CDMOR, LH707, 2g) and l
      cystine bis(N'-methylpiperazide) (CDNMP, LH708, 2h) are the most potent
      inhibitors of l-cystine crystallization.

PMID- 29571574
TI  - Re: Zhangqun Ye, Guohua Zeng, Huan Yang, et al. Efficacy and Safety of Tamsulosin
      in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A
      Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Eur Urol
      2018;73:385-91: Medical Expulsive Therapy for Distal Ureteral Stones: Call the
      Jury Back.

PMID- 29571573
TI  - Sulfoximines as potent RORgamma inverse agonists.
AB  - Progress in the identification of suitable RORgamma inverse agonists as clinical
      candidates has been hampered by the high lipophilicity that seems required for
      high potency on this nuclear receptor. In this context, we decided to focus on
      the replacement of the hydroxymethyl group found on known modulators to determine
      if more polarity could be tolerated in this position. SAR of the replacement of
      this moiety is presented in this article leading to the identification of
      sulfoximine derivatives as potent modulators with pharmacological activity in the
      in vivo mouse Imiquimod psoriasis model.

PMID- 29571575
TI  - [Non-ossifying fibroma].

PMID- 29571576
TI  - [Mondor's disease].

PMID- 29571577
TI  - [Thrombus or plaque?: Usefulness of ultrasound as a diagnostic tool in family
      medicine].

PMID- 29571578
TI  - Taking forward the Stop TB Partnership and World Health Organization Joint Theme
      for World TB Day March 24th 2018 - "Wanted: Leaders for a TB-Free World. You can
      make history. End TB".

PMID- 29571579
TI  - A pan-European ring trial to validate an International Standard for detection of
      Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus in seafoods.
AB  - Globally, vibrios represent an important and well-established group of bacterial
      foodborne pathogens. The European Commission (EC) mandated the Comite de European
      Normalisation (CEN) to undertake work to provide validation data for 15 methods
      in microbiology to support EC legislation. As part of this mandated work
      programme, merging of ISO/TS 21872-1:2007, which specifies a horizontal method
      for the detection of V. parahaemolyticus and V. cholerae, and ISO/TS 21872
      2:2007, a similar horizontal method for the detection of potentially pathogenic
      vibrios other than V. cholerae and V. parahaemolyticus was proposed. Both parts
      of ISO/TS 21872 utilized classical culture-based isolation techniques coupled
      with biochemical confirmation steps. The work also considered simplification of
      the biochemical confirmation steps. In addition, because of advances in molecular
      based methods for identification of human pathogenic Vibrio spp. classical and
      real-time PCR options were also included within the scope of the validation.
      These considerations formed the basis of a multi-laboratory validation study with
      the aim of improving the precision of this ISO technical specification and
      providing a single ISO standard method to enable detection of these important
      foodborne Vibrio spp.. To achieve this aim, an international validation study
      involving 13 laboratories from 9 countries in Europe was conducted in 2013. The
      results of this validation have enabled integration of the two existing technical
      specifications targeting the detection of the major foodborne Vibrio spp.,
      simplification of the suite of recommended biochemical identification tests and
      the introduction of molecular procedures that provide both species level
      identification and discrimination of putatively pathogenic strains of V.
      parahaemolyticus by the determination of the presence of theromostable direct and
      direct related haemolysins. The method performance characteristics generated in
      this have been included in revised international standard, ISO 21872:2017,
      published in July 2017.

PMID- 29571580
TI  - [Influenzae and pneumococcal vaccination rate in an internal medicine ward].
AB  - INTRODUCTION: Vaccination against influenza virus and Streptococcus pneumoniae is
      a global health priority and authorities, on the basis of recent publications,
      have recently updated French recommendations. The aim of this study was to
      describe the influenzae and pneumococcal vaccination's rate in an internal
      medicine ward. MATERIAL AND METHODS: All patients consecutively hospitalized
      during a 10 week-period in an internal medicine ward were included. The reasons
      for non-vaccination and the impact of an educational program for corrective
      measures were reported. RESULTS: Overall, 198 consecutive patients were included;
      93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal
      vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of
      them were vaccinated against these microorganisms, respectively. Prior
      pneumococcal vaccination was more frequently observed in immunocompromised
      patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but
      no significant difference was observed for influenza vaccine. Corrective measures
      were initiated in 46 patients (39%), non-immunized against S. pneumoniae.
      CONCLUSION: These results underline the very low prevalence of pneumococcal
      vaccination rate in at-risk hospitalized patients, as compared with influenza,
      despite recent recommendations.

PMID- 29571581
TI  - [Simulation-based learning development: More haste, less speed].

PMID- 29571582
TI  - Coordinated control of micro-grid based on distributed moving horizon control.
AB  - This paper proposed the distributed moving horizon coordinated control scheme for
      the power balance and economic dispatch problems of micro-grid based on
      distributed generation. We design the power coordinated controller for each
      subsystem via moving horizon control by minimizing a suitable objective function.
      The objective function of distributed moving horizon coordinated controller is
      chosen based on the principle that wind power subsystem has the priority to
      generate electricity while photovoltaic power generation coordinates with wind
      power subsystem and the battery is only activated to meet the load demand when
      necessary. The simulation results illustrate that the proposed distributed moving
      horizon coordinated controller can allocate the output power of two generation
      subsystems reasonably under varying environment conditions, which not only can
      satisfy the load demand but also limit excessive fluctuations of output power to
      protect the power generation equipment.

PMID- 29571583
TI  - Reachable set estimation for Takagi-Sugeno fuzzy systems against unknown output
      delays with application to tracking control of AUVs.
AB  - In this paper, we address the problem of reachable set estimation for continuous
      time Takagi-Sugeno (T-S) fuzzy systems subject to unknown output delays. Based on
      the reachable set concept, a new controller design method is also discussed for
      such systems. An effective method is developed to attenuate the negative impact
      from the unknown output delays, which likely degrade the performance/stability of
      systems. First, an augmented fuzzy observer is proposed to capacitate a
      synchronous estimation for the system state and the disturbance term owing to the
      unknown output delays, which ensures that the reachable set of the estimation
      error is limited via the intersection operation of ellipsoids. Then, a
      compensation technique is employed to eliminate the influence on the system
      performance stemmed from the unknown output delays. Finally, the effectiveness
      and correctness of the obtained theories are verified by the tracking control of
      autonomous underwater vehicles.

PMID- 29571585
TI  - Molecular Progression Risk Score for Prediction of Muscle Invasion in Primary T1
      High-Grade Bladder Cancer.
AB  - BACKGROUND: Pathologic T1 high-grade (pT1HG) bladder cancer (BC) is characterized
      by a high progression rate and constitutes an important clinical challenge;
      however, there is no consensus on the prediction of progression in pT1HG BC. The
      purpose of this study was to validate previously published molecular progression
      risk score (MoPRS) for predicting muscle-invasive disease in pT1HG BC. MATERIALS
      AND METHODS: The expression of an 8-gene progression-related classifier
      identified from microarray data was analyzed by real-time PCR, and the MoPRS was
      calculated in 121 newly recruited patients with pT1HG BC. Progression was defined
      as muscle invasion or metastasis. RESULTS: Overall, the disease of 28 patients
      (23.1%) progressed to muscle-invasive BC during the median follow-up of 63.7
      (interquartile range, 17.6-96.4) months. The MoPRS was significantly higher in
      1973 World Health Organization grade 3 than grade 2 tumors (P = .004). Early
      development of invasive BC was more prevalent in the highest quartile MoPRS group
      than in the lowest to 75th percentile MoPRS groups according to Kaplan-Meier
      analysis. Multivariate Cox regression analysis revealed that the MoPRS was an
      independent predictor of invasive BC, either as a continuous variable (hazard
      ratio, 1.624; 95% confidence interval, 1.266-2.082; P < .001) or as a categorical
      variable (hazard ratio, 3.089; 95% confidence interval, 1.335-7.150; P = .008).
      CONCLUSION: The MoPRS was an independent prognostic factor for identifying
      patients at high risk of invasive BC in patients with pT1HG BC. This scale may
      help identify patients who could benefit from more aggressive therapeutic
      intervention such as early cystectomy.

PMID- 29571584
TI  - Using Genetic and Epigenetic Markers to Improve Differential Diagnosis of
      Prostate Cancer and Benign Prostatic Hyperplasia by Noninvasive Methods in
      Mexican Patients.
AB  - BACKGROUND: Prostate cancer (PCa) is the most common malignancy in Mexican men.
      Serum prostate-specific antigen (PSA) is the usual noninvasive biomarker used for
      its detection. Its low specificity can increase the number of unnecessary
      prostate biopsies and the incidence of unpleasant complications for patients. The
      androgen-receptor gene (AR-CAG) repeat length and the percentage of promoter
      methylation (PPM) of genes glutathione-S-transferase P1 (GSTP1) and Ras
      association domain family 1 isoform A (RASSF1A) improve PCa detection. As an
      option for noninvasive assessment, we evaluated a combined analysis of all these
      biomarkers. PATIENTS AND METHODS: A total of 186 patients scheduled for biopsy
      were included in the present study. PSA and AR-CAG repeats were analyzed in blood
      samples. The PPM of GSTP1 and RASSF1A genes was estimated in prostate tissue and
      urinary sediment cells (USCs) and plasma DNA using quantitative methylation
      specific polymerase chain reaction. The predictive values for PCa and benign
      prostatic hyperplasia (BPH), logistic regression analysis, receiver operating
      characteristic curve, and decision curve analysis were used to assess the
      differential diagnosis. RESULTS: Statistically significant differences between
      PCa and BPH patients were observed for all biomarkers, with higher positive and
      negative predictive values when all biomarkers were included in the analysis,
      attaining USC values of 89.2% and 78.0%, respectively. The differential diagnosis
      accuracy of PSA (area under the curve, 0.59) increased to 0.70 and 0.68,
      respectively, when the combined analysis of PPM of RASSF1Aplasma or GSTP1AUSC and
      AR-CAG repeats was performed. Decision curve analysis showed the utility of the
      combined analysis to decrease the number of unnecessary biopsies. CONCLUSION: The
      results showed that combined analysis of the proposed biomarkers in plasma and
      USCs significantly increased the confidence for the differential diagnosis for
      PCa and BPH. This noninvasive practice might help in the early detection of PCa
      and patient follow-up, avoiding to some extent unnecessary prostate biopsies.

PMID- 29571586
TI  - Personalized Transcranial Magnetic Stimulation in Psychiatry.
AB  - Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation
      technique that allows for modulating the activity of local neural populations and
      related neural networks. TMS is touted as a viable intervention to normalize
      brain activity and alleviate some psychiatric symptoms. However, TMS
      interventions are known to be only moderately reliable, and the efficacy of such
      therapies remains to be proven for psychiatric disorders other than depression.
      We review new opportunities to personalize TMS interventions using neuroimaging
      and computational modeling, aiming to optimize treatment to suit particular
      individuals and clinical subgroups. Specifically, we consider the prospect of
      improving the efficacy of existing TMS interventions by parsing broad diagnostic
      categories into biologically and clinically homogeneous biotypes. Biotypes can
      provide distinct treatment targets for optimized TMS interventions. We further
      discuss the utility of computational models in refining TMS personalization and
      efficiently establishing optimal cortical targets for distinct biotypes.
      Personalizing cortical stimulation targets, treatment frequencies, and
      intensities can improve the therapeutic efficacy of TMS and potentially establish
      noninvasive brain stimulation as a viable treatment for psychiatric symptoms.

PMID- 29571587
TI  - The effects of red tide (Karenia brevis) on reflex impairment and mortality of
      sublegal Florida stone crabs, Menippe mercenaria.
AB  - The Florida stone crab, Menippe mercenaria, is a major commercial fishery that
      occurs primarily along Florida's west coast, where harmful algal blooms of
      Karenia brevis frequently develop. To determine sublethal and lethal effects of
      K. brevis on M. mercenaria, we exposed sublegal stone crabs to three seawater
      treatments in laboratory conditions: no K. brevis (control), a low-toxin K.
      brevis strain (Wilson LT), and a toxic K. brevis (New Pass strain). Total food
      consumed, reflex impairment and survivorship of each crab was monitored
      throughout the nine-day experiment. Crabs in the toxic treatment consumed 67%
      less food. The probability of an individual losing a reflex significantly
      increased with time (days), and there was a 42% decrease in survivorship in the
      toxic treatment. This is the first study to demonstrate negative effects of K.
      brevis on the stone crab, presenting the critical need of further investigation
      to fully understand how red tide may impact sustainability of the fishery.

PMID- 29571588
TI  - Settlement performance of the Mediterranean reef-builders Dendropoma cristatum
      (Biondi 1859) in response to natural bacterial films.
AB  - The gastropod Dendropoma cristatum is a biogenic engineer of the central
      Mediterranean, forming reefs along the lower rocky intertidal fringe with a
      remarkable ecological role. To understand whether reef-associated biofilm
      cultivable bacterial and biofilm ageing may trigger the settlement of the
      juvenile snails, a combination of laboratory techniques and field experiments was
      used. Reef-associated biofilm cultivable bacteria were isolated, and a settlement
      choice experiment was performed in situ on artificial biofilms composed of i) a
      mixture of six biofilm-forming selected isolates, ii) all the cultivable
      bacteria, and iii) 13-, 23-, 32-day old biofilms formed under natural conditions.
      Overall, settlement rate significantly differed among biofilm treatments (p <
      0.0001). A significant positive correlation between biofilm ageing and juvenile
      D. cristatum settlement was assessed (r = 0.69 (p < 0.001), whereas the biofilm
      bacterial composition (relatively to the cultivable fraction) did not show any
      effect on the vermetid's settlement rate.

PMID- 29571589
TI  - Impact of weight loss on epicardial fat and carotid intima media thickness after
      laparoscopic sleeve gastrectomy: A prospective study.
AB  - BACKGROUND AND AIMS: Cardiovascular disease (CVD) is one of the leading causes of
      mortality in obese patients. We aimed to investigate the influence of significant
      weight loss following laparoscopic sleeve gastrectomy (LSG) on carotid intima
      media thickness (CIMT) and epicardial fat thickness (EFT) which are the
      independent predictors of subclinical atherosclerosis. METHODS AND RESULTS:
      Patients were recruited for standard indications. A total of 105 patients (79
      women and 26 men) with the mean age of 43.61 +/- 12.42 were prospectively
      enrolled. On B-mode duplex ultrasound; the mean CIMT at the far wall of both left
      and right common carotid arteries were measured. EFT was measured on the free
      wall of the right ventricle at end-diastole from the parasternal long-axis view
      by standard transthorasic 2D echocardiography. Delta (Delta) values were obtained
      by subtracting sixth month values from the baseline values. Body mass index (BMI)
      was significantly reduced from 46.95 +/- 7.54 to 33.54 +/- 6.41 kg/m2 (p < 0.001)
      in sixth months after LSG. Both EFT and CIMT were significantly decreased after
      surgery (8.68 +/- 1.95 mm vs. 7.41 +/- 1.87 mm; p < 0.001 and 0.74 +/- 0.13 mm
      vs. 0.67 +/- 0.11 mm; p < 0.001 respectively). A significant correlation between
      DeltaEFT and DeltaBMI (r = 0.431, p < 0.001) was shown. DeltaCIMT is
      significantly correlated with DeltaEFT, DeltaBMI and Delta systolic blood
      pressure (r = 0.310, r = 0.285 and r = 0.231 respectively, p < 0.05 for all). In
      multivariate stepwise linear regression analysis; among variables only DeltaBMI
      was the independent predictor of DeltaEFT (beta = 153, p = 0.001). CONCLUSION:
      Early atherosclerotic structural changes may be reversed or improved by sustained
      weight loss after LSG in asymptomatic obese patients.

PMID- 29571590
TI  - Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal
      children: Comparison of definitions.
AB  - BACKGROUND AND AIMS: The early onset of cardio-metabolic abnormalities, known as
      metabolically unhealthy (MU) status, is highly associated with obesity and
      cardiovascular disease (CVD), as well as with increased morbidity and mortality
      later in life. Given the lack of a consensus MU classification for prepubertal
      children, we aimed to compare available MU definitions in terms of their
      association with CVD risk biomarkers. METHODS AND RESULTS: A total of 930
      prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years
      were recruited, anthropometric measures were taken and biomarkers were analyzed.
      Children were classified using eight MU definitions based on different cut-offs
      for blood pressure, triacylglycerides, high-density lipoprotein cholesterol,
      glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU
      prevalence in children with overweight/obesity ranged between 30% and 60% across
      definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and
      total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of
      adiponectin were lower, in MU compared to MH children with overweight/obesity.
      Linear regression analyses confirmed the contribution of MPO and tPAI-1
      concentrations to MU status, with most significant results derived from
      definitions that use age and sex-specific criteria and that account for HOMA-IR.
      CONCLUSION: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal
      MU children irrespective of having normal-weight or overweight/obesity. Inclusion
      of age and sex-specific cut-offs for cardio-metabolic components as well as
      insulin resistance criteria increases the quality of MU definitions as seen by
      their stronger association with CVD biomarkers concentrations.

PMID- 29571591
TI  - Corrigendum to "Sirtuin 3 rescues neurons through the stabilisation of
      mitochondrial biogenetics in the virally-expressing mutant alpha-synuclein rat
      model of parkinsonism" [Neurobiol. Dis. 106 (2018) 133-146].

PMID- 29571592
TI  - Risk of maternal mortality in women with severe anaemia during pregnancy and post
      partum: a multilevel analysis.
AB  - BACKGROUND: Anaemia affects as many as half of all pregnant women in low-income
      and middle-income countries, but the burden of disease and associated maternal
      mortality are not robustly quantified. We aimed to assess the association between
      severe anaemia and maternal death with data from the WHO Multicountry Survey on
      maternal and newborn health. METHODS: We used multilevel and propensity score
      regression analyses to establish the relation between severe anaemia and maternal
      death in 359 health facilities in 29 countries across Latin America, Africa, the
      Western Pacific, eastern Mediterranean, and southeast Asia. Severe anaemia was
      defined as antenatal or postnatal haemoglobin concentrations of less than 70 g/L
      in a blood sample obtained before death. Maternal death was defined as death any
      time after admission until the seventh day post partum or discharge. In
      regression analyses, we adjusted for post-partum haemorrhage, general
      anaesthesia, admission to intensive care, sepsis, pre-eclampsia or eclampsia,
      thrombocytopenia, shock, massive transfusion, severe oliguria, failure to form
      clots, and severe acidosis as confounding variables. These variables were used to
      develop the propensity score. FINDINGS: 312 281 women admitted in labour or with
      ectopic pregnancies were included in the adjusted multilevel logistic analysis,
      and 12 470 were included in the propensity score regression analysis. The
      adjusted odds ratio for maternal death in women with severe anaemia compared with
      those without severe anaemia was 2.36 (95% CI 1.60-3.48). In the propensity score
      analysis, severe anaemia was also associated with maternal death (adjusted odds
      ratio 1.86 [95% CI 1.39-2.49]). INTERPRETATION: Prevention and treatment of
      anaemia during pregnancy and post partum should remain a global public health and
      research priority. FUNDING: Barts and the London Charity.

PMID- 29571593
TI  - Maternal anaemia and risk of mortality: a call for action.

PMID- 29571595
TI  - "Sedation is tricky": A qualitative content analysis of nurses' perceptions of
      sedation administration in mechanically ventilated intensive care unit patients.
AB  - INTRODUCTION: Critical care nurses are responsible for administering sedative
      medications to mechanically ventilated patients. With significant advancements in
      the understanding of the impact of sedative exposure on physiological and
      psychological outcomes of ventilated patients, updated practice guidelines for
      assessment and management of pain, agitation, and delirium in the intensive care
      unit were released in 2013. The primary aim of this qualitative study was to
      identify and describe themes derived from critical care nurses' comments
      regarding sedation administration practices with mechanically ventilated
      patients. METHODS: This is a qualitative content analysis of secondary text data
      captured through a national electronic survey of members of the American
      Association of Critical-Care Nurses. A subsample (n = 67) of nurses responded to
      a single, open-ended item at the end of a survey that evaluated nurses'
      perceptions of current sedation administration practices. FINDINGS: Multiple
      factors guided sedation administration practices, including individual patient
      needs, nurses' synthesis of clinical evidence, application of best practices, and
      various personal and professional practice perspectives. Our results also
      indicated nurses desire additional resources to improve their sedation
      administration practices including more training, better communication tools, and
      adequate staffing. CONCLUSIONS: Critical care nurses endorse recommendations to
      minimise sedation administration when possible, but a variety of factors,
      including personal perspectives, impact sedation administration in the intensive
      care unit and need to be considered. Critical care nurses continue to encounter
      numerous challenges when assessing and managing sedation of mechanically
      ventilated patients.

PMID- 29571594
TI  - Occurrence of neoplasms in individuals with congenital, severe GH deficiency from
      the Itabaianinha kindred.
AB  - Growth hormone (GH) and the insulin-like growth factor I (IGF-I) have cell
      proliferative and differentiation properties. Whether these hormones have a role
      in mutagenesis is unknown. Nevertheless, severe IGF-I deficiency seems to confer
      protection against the development of neoplasms. Here, we report five cases of
      adult patients with severe and congenital isolated GH deficiency (IGHD) due to
      the c.57+1G>A mutation in the GHRH receptor gene, who developed tumors. Four GH
      naive subjects presented skin tumors: a 42-year-old man with a fibroepithelial
      polyp, a 53-year-old woman and two men (59 and 56 years old) with epidermoid skin
      cancers. One of these died from it after three surgeries and radiotherapy. The
      fifth patient was a 25-year-old woman, who had intermittently received GH
      replacement therapy (GHRT) from age 11 to 18, who developed an ependymoma
      extending from the fourth ventricle to the end of the thoracic spine. She
      underwent three surgical procedures, without obvious evidence of tumor recurrence
      during the six years follow up. These observations suggest that severe IGHD does
      not protect completely from development of tumors.

PMID- 29571596
TI  - Bereaved parents' experiences of the police in the paediatric intensive care
      unit.
AB  - BACKGROUND: A child's death in the intensive care unit is often sudden and
      unexpected, requiring the involvement of the state coroner to investigate both
      the cause and the circumstances surrounding the death. This process often
      involves the police, who arrive in intensive care to identify the body and
      collect statements from the parents. At present, very little is known about
      parents' experiences of this process. OBJECTIVES: To explore bereaved parents'
      experiences of police presence in intensive care, as part of routine coronial
      investigations. The findings arose from a larger study on bereaved parents'
      experiences of the death of a child in the intensive care unit. METHODS:
      Secondary analysis of incidental data from a larger grounded theory study. Nine
      bereaved parents from two paediatric intensive care units (PICUs) mentioned
      police presence in the PICU during their original audio-recorded, semistructured
      interviews. These data were extracted, and thematic analysis techniques were used
      to identify key themes. RESULTS: Three main concepts were identified with the
      parents' experiences: (i) timing of police interviews; (ii) the impacts of police
      presence; and (iii) the demeanour of the officers. Overall, the parents'
      experiences of police presence were negative. They felt that police arrived too
      soon after their child's death and took too long taking their statements,
      hindering their ability to say goodbye. The presence of police officers also made
      parents feel as though they were being accused of involvement in their child's
      death. Finally, several participants also experienced inappropriate or
      unsympathetic attitudes from the police officers attending their child's death.
      CONCLUSIONS: Findings from our study indicate that parents' experiences of police
      presence in the PICU as part of a coronial investigation may be negative, leaving
      lasting impressions on their experiences of their child's death. These findings
      provide areas for improvements in care delivery and the treatment of newly
      bereaved parents during the early phases of a coronial investigation.

PMID- 29571597
TI  - A cross-sectional study of predictors of pain control during the transition from
      the surgical intensive care unit to surgical ward.
AB  - BACKGROUND: The transition of patients from the intensive care unit (ICU) to the
      ward is a complicated process and patients may be at risk of increased levels of
      pain. OBJECTIVES: The primary objective was to identify predictors of pain during
      the transition from the surgical ICU to the surgical ward. The secondary
      objective was to describe the patient pain experience during this transition.
      METHODS: This was a cross-sectional study conducted at an academic medical centre
      in the United States. Patients who were discharged from the ICU were interviewed
      regarding their pain during transition from ICU to the ward using the Revised
      American Pain Society Patient Outcome Questionnaire (APS-POQ-R). The primary
      outcome measures were the total score of this validated instrument (0-180 points)
      and score of the pain severity and sleep interference subscale (0-50 points).
      Predictors of pain control during this 24-h transition period were identified
      using linear regression analysis. RESULTS: A total of 50 patients were included.
      After transition from the ICU, the median score on the APS-POQ-R was 45 (Q1 29 to
      Q3 74), and the median score on the pain severity and sleep interference subscale
      was 23 (Q1 15 to Q3 30). After adjusting for sex in a multivariate model, mean
      pain score in the preceding 24 h of ICU stay explained 31% of the variation in
      total APS-POQ-R score and 39% of variation in the pain severity and sleep
      interference subscale. Age, sex, race, type of surgery, number of surgeries, and
      opioid dose in the 24-h period before transfer were not significantly associated
      with either outcome measure. The worst pain experienced by patients during
      transfer was severe (i.e. score >=7 on 0 to 10 scale) in 90% (n = 45) of
      patients. For 70% (n = 35) of patients, severe pain persisted for more than 50%
      of the time during the transition period. CONCLUSION: Pain scores in the last 24
      h of ICU stay is a predictor of total APS-POQ-R score and pain severity and sleep
      interference subscale score.

PMID- 29571598
TI  - Behavioral Profile of Children With Vocal Fold Nodules-A Case-control Study.
AB  - OBJECTIVES: The aim of this case-control study was to evaluate the overall
      behavior of children with vocal fold nodules (VNs). METHODS: The study group
      included children with VNs between 4 and 15 years old diagnosed using fiberoptic
      video laryngoscopy with stroboscopy in a tertiary university hospital. As a
      control group, children between 4 and 13 years old without VNs, routinely
      followed up in a primary care facility, were included in the study. Parents of
      the participants completed the parent-proxy strengths and difficulties
      questionnaire (SDQ), a brief behavioral screening questionnaire designed for
      children. The SDQ evaluates emotional, conduct, and peer problems, and also
      focuses on hyperactivity and prosocial behavior. Children are classified into
      "normal," "borderline," or "abnormal" according to the total SDQ score. RESULTS:
      Twenty-seven children (24 boys and 3 girls) with VNs and 41 controls (33 boys and
      8 girls) were enrolled in the study. The two groups did not differ significantly
      in age or gender (P > 0.05). Statistical analysis revealed that 52% individuals
      of the VNs group presents borderline or abnormal overall behavioral, which is
      statistically different from the general population (P < 0.001). Total,
      hyperactivity, and prosocial SDQ subscales were statistically different between
      study groups (P < 0.05). CONCLUSIONS: Our findings suggest association between
      VNs and hyperactivity and also with poorer prosocial behaviors in children for
      the first time. We propose that every child with VNs must be evaluated from a
      behavioral point of view to detect and to treat potential underlying
      psychological conditions that may interfere with VNs treatment and prognosis.

PMID- 29571599
TI  - Similitude assessment method for comparing PMHS response data from impact loading
      across multiple test devices.
AB  - Biological tissue testing is inherently susceptible to the wide range of
      variability specimen to specimen. A primary resource for encapsulating this range
      of variability is the biofidelity response corridor or BRC. In the field of
      injury biomechanics, BRCs are often used for development and validation of both
      physical, such as anthropomorphic test devices, and computational models. For the
      purpose of generating corridors, post-mortem human surrogates were tested across
      a range of loading conditions relevant to under-body blast events. To
      sufficiently cover the wide range of input conditions, a relatively small number
      of tests were performed across a large spread of conditions. The high volume of
      required testing called for leveraging the capabilities of multiple impact test
      facilities, all with slight variations in test devices. A method for assessing
      similitude of responses between test devices was created as a metric for
      inclusion of a response in the resulting BRC. The goal of this method was to
      supply a statistically sound, objective method to assess the similitude of an
      individual response against a set of responses to ensure that the BRC created
      from the set was affected primarily by biological variability, not anomalies or
      differences stemming from test devices.

PMID- 29571600
TI  - Stability basin estimates fall risk from observed kinematics, demonstrated on the
      Sit-to-Stand task.
AB  - The ability to quantitatively measure stability is essential to ensuring the
      safety of locomoting systems. While the response to perturbation directly
      reflects the stability of a motion, this experimental method puts human subjects
      at risk. Unfortunately, existing indirect methods for estimating stability from
      unperturbed motion have been shown to have limited predictive power. This paper
      leverages recent advances in dynamical systems theory to accurately estimate the
      stability of human motion without requiring perturbation. This approach relies on
      kinematic observations of a nominal Sit-to-Stand motion to construct an
      individual-specific dynamic model, input bounds, and feedback control that are
      then used to compute the set of perturbations from which the model can recover.
      This set, referred to as the stability basin, was computed for 14 individuals,
      and was able to successfully differentiate between less and more stable Sit-to
      Stand strategies for each individual with greater accuracy than existing methods.

PMID- 29571601
TI  - High circulating CD4+CD25hiFOXP3+ T-cell sub-population early after lung
      transplantation is associated with development of bronchiolitis obliterans
      syndrome.
AB  - BACKGROUND: Chronic bronchiolitis obliterans syndrome (BOS) remains a major
      limitation for long-term survival after lung transplantation. The immune
      mechanisms involved and predictive biomarkers have yet to be identified. The
      purpose of this study was to determine whether peripheral blood T-lymphocyte
      profile could predict BOS in lung transplant recipients. METHODS: An in-depth
      profiling of CD4+ and CD8+ T cells was prospectively performed on blood cells
      from stable (STA) and BOS patients with a longitudinal follow-up. Samples were
      analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis,
      and at an intermediate time-point at 6 to 12 months before BOS diagnosis.
      RESULTS: Although no significant difference was found for T-cell compartments at
      BOS diagnosis or several months beforehand, we identified an increase in the
      CD4+CD25hiFoxP3+ T-cell sub-population in BOS patients at 1 and 6 months after
      transplantation (3.39 +/- 0.40% vs 1.67 +/- 0.22% in STA, p < 0.001). A
      CD4+CD25hiFoxP3+ T-cell threshold of 2.4% discriminated BOS and stable patients
      at 1 month post-transplantation. This was validated on a second set of patients
      at 6 months post-transplantation. Patients with a proportion of CD4+CD25hiFoxP3+
      T cells up to 2.4% in the 6 months after transplantation had a 2-fold higher risk
      of developing BOS. CONCLUSIONS: This study is the first to report an increased
      proportion of circulating CD4+CD25hiFoxP3+ T cells early post-transplantation in
      lung recipients who proceed to develop BOS within 3 years, which supports its use
      as a BOS predictive biomarker.

PMID- 29571603
TI  - Low grade parotid mucoepidermoid carcinoma with tumour associated lymphoid
      proliferation ("Warthin-like") and CRTC1-MAML2 fusion transcript: Definitive
      diagnosis with molecular investigation only.

PMID- 29571602
TI  - Heart failure after the Norwood procedure: An analysis of the Single Ventricle
      Reconstruction Trial.
AB  - BACKGROUND: Heart failure results in significant morbidity and mortality in young
      children with hypoplastic left heart syndrome (HLHS) after the Norwood procedure.
      METHODS: We studied subjects enrolled in the prospective Single Ventricle
      Reconstruction (SVR) Trial who survived to hospital discharge after a Norwood
      operation and were followed up to age 6 years. The primary outcome was heart
      failure, defined as heart transplant listing after Norwood hospitalization, death
      attributable to heart failure, or symptomatic heart failure (New York Heart
      Association [NYHA] Class IV). Multivariate modeling was undertaken using Cox
      regression methodology to determine variables associated with heart failure.
      RESULTS: Of the 461 subjects discharged home following a Norwood procedure, 66
      (14.3%) met the criteria for heart failure. Among these, 15 died from heart
      failure, 39 were listed for transplant (22 had a transplant, 12 died after
      listing, and 5 were alive and not yet transplanted), and 12 had NYHA Class IV
      heart failure but were never listed. The median age at heart failure
      identification was 1.28 (interquartile range 0.30 to 4.69) years. Factors
      associated with early heart failure included post-Norwood lower fractional area
      change, need for extracorporeal membrane oxygenation, non-Hispanic ethnicity,
      Norwood perfusion type, and total support time (p < 0.05). CONCLUSIONS: By 6
      years of age, heart failure developed in nearly 15% of children after the Norwood
      procedure. Although transplant listing was common, many patients died from heart
      failure before receiving a transplant or without being listed. Shunt type did not
      impact the risk of developing heart failure.

PMID- 29571604
TI  - A new resting metabolic rate equation for women with class III obesity.
AB  - OBJECTIVE: Resting metabolic rate (RMR) is an important parameter to guide the
      nutritional therapy of class III obese patients. The aims of the present study
      were to develop a predictive equation for RMR estimation in class III obese women
      using anthropometric indicators and to compare indirect calorimetry with other
      predictive equations. METHODS: This was a cross-sectional study on women with
      class III obesity (body mass index >40 kg/m2). Weight, height, fat-free mass, fat
      mass, and RMR of all individuals were measured. Multiple linear regression was
      used to determine the new RMR equation and the Bland-Altman plot was used to
      analyze the agreement between indirect calorimetry and the results of predictive
      equations. RESULTS: We evaluated 101 women with obesity class III and a mean age
      of 36.3 +/- 10 y. The anthropometric and body composition variables used in the
      new equation had a coefficient of determination of 0.80, and a significant
      influence on RMR (P = 0.01). Harris-Benedict and World Health Organization
      equations showed similar bias and limits (181.6, +2 SD = 765.5, -2 SD = -402.2;
      156.4, +2 SD = 799.4, -2 SD = -486.6, respectively). The Mifflin-St Jeor and Owen
      equations showed large clinical bias (mean, 239.2 and 463.9, respectively), and a
      tendency to overestimate RMR. CONCLUSION: The prediction equations tested in the
      study had low accuracy in estimating RMR of women with class III obesity.
      However, our equation was developed specifically for this population, using
      variables known to influence their energy expenditure.

PMID- 29571605
TI  - Emotional eating behavior hinders body weight loss in women after Roux-en-Y
      gastric bypass surgery.
AB  - OBJECTIVE: Successful weight loss and maintenance after Roux-en-Y gastric bypass
      (RYGB) may be related to eating behavior. The aim of this study was to assess the
      eating behavior domains that prevail in women during the RYGB postoperative
      period and their associations with surgery outcome. METHODS: This cross-sectional
      study investigated eating behavior in 95 women (47.3 +/- 9.8 y old)  >= 2 y after
      Roux-en-Y gastric bypass. Patients were grouped according to surgery outcome:
      successful group (SG; n = 67), defined as having lost >= 50% of the preoperative
      excess weight loss (EWL), and an unsuccessful group (UG; n = 28). Mean
      postoperative time was 59.5 +/- 21.2 mo (55.7 +/- 19.9 in the SG and 68.6 +/-
      21.9 in the UG). The short version of the Three-Factor Eating Questionnaire was
      used to assess cognitive restraint, emotional eating, and uncontrolled eating
      behaviors. Multivariate analysis was used to investigate associations between
      eating behavior scores and EWL. RESULTS: The highest score in both groups was for
      the cognitive restraint domain, followed by emotional and uncontrolled eating.
      Emotional eating was negatively associated with percentage of EWL (beta = -0.286;
      P = 0.033), regardless of age, educational attainment, and postoperative time.
      CONCLUSION: The cognitive restraint domain was the main type of eating behavior
      observed, and patients with higher emotional eating score were at a higher risk
      for having insufficient weight loss after RYGB. These results indicate the
      relevance of monitoring emotional components during the long-term nutritional
      follow-up of bariatric patients to achieve better surgery outcomes.

PMID- 29571606
TI  - Processed meat and selected hormone-related cancers.
AB  - OBJECTIVE: To assess and quantify the association between processed meat
      consumption and cancers of the breast, endometrium, ovary, and prostate. METHODS:
      Data were derived from an integrated network of hospital-based case-control
      studies conducted between 1982 and 2006 in various Italian areas. These studies
      included 5981 cases of cancer of the breast, 992 of the endometrium, 2002 of the
      ovary, 1582 of the prostate, and a total of 16 394 controls with data on
      processed meat. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated by unconditional multiple logistic regression models, adjusted for
      major recognized confounders for each cancer site. RESULTS: The median
      consumption of processed meat in this population was 2 portions per wk in each
      cancer-specific cases, controls, and overall, corresponding to 100 g/wk. The OR
      for the highest (>=20 g/d) compared with lowest (<10 g/d) category of processed
      meat consumption was 1.16 (95% CI 1.06-1.28) for breast, 1.31 (95% CI 1.07-1.60)
      for endometrial, 1.49 (95% CI 1.30-1.71) for ovarian, and 0.89 (95% CI 0.74-1.07)
      for prostate cancer. CONCLUSION: In this case-control study, we found some excess
      risks of high processed meat consumption with female hormone-related cancers.
      Conversely, no association with prostate cancer was found in men.

PMID- 29571607
TI  - Vitamin D deficiency and high serum IL-6 concentration as risk factors for tubal
      factor infertility in Chinese women.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between 25
      hydroxyvitamin-D [25(OH)D] and female infertility and to further explore the role
      of inflammatory cytokines. METHOD: We recruited 356 infertile women diagnosed
      with tubal factor infertility (TFI) or polycystic ovary syndrome (PCOS) or
      endometriosis, as well as 180 fertile women. Serum concentrations of 25(OH)D,
      interleukin (IL)-6, IL-1 beta, and interferon-alpha were measured. RESULTS: The
      25(OH)D concentration in TFI women was the lowest (16.9 ng/mL) and was
      significantly different from that in the fertile women (19.4 ng/mL; P <0.05)];
      whereas women with TFI had higher IL-6 concentrations. After adjusting for
      confounders, 25(OH)D deficiency presented a risk factor for TFI (odds ratio [OR],
      4.2; 95% confidence interval [CI], 1.5-11.3). There was a dose-effect relation
      between IL-6 tertiles and TFI: the higher the IL-6, the higher the risk for TFI
      (middle versus low: OR, 3.7; 95% CI, 1.5-9.5; high versus low: OR, 13.2; 95% CI,
      4.8-36.4). IL-6 showed a negative correlation with 25(OH)D (r = -0.19). Women
      with both high IL-6 and low 25(OH)D had the highest risk for TFI (OR, 10.6; 95%
      CI, 4.2-26.3). CONCLUSIONS: Both vitamin D deficiency and high serum IL-6
      concentration are risk factors for TFI. Serum 25(OH)D concentration was
      significantly and negatively correlated with serum IL-6. There was an interaction
      between IL-6 and 25(OH)D for the risk for TFI-related infertility. We
      hypothesized that vitamin D might reduce the risk for TFI through suppressing the
      production of IL-6.

PMID- 29571608
TI  - Physicochemical stable standard all-in-one parenteral nutrition admixtures for
      infants and children in accordance with the ESPGHAN/ESPEN guidelines.
AB  - OBJECTIVE: Because there are almost no standard all-in-one parenteral nutrition
      admixtures available for infants and children, the aim was to develop standard
      two-compartment parenteral nutrition bags for different weight categories based
      on the ESPGHAN/ESPEN (European Society of Paediatric Gastroenterology, Hepatology
      and Nutrition/European Society for Clinical Nutrition and Metabolism) guidelines.
      The 1 g/kg/d lipid version for the 3 to 10 kg weight category (PED1) was assessed
      for short- and long-term physicochemical stability with the ability to add
      additional electrolytes (PED1+E). METHODS: The lipid compartment A and the all-in
      one admixture of A + B + vitamins + trace elements were assessed physically by
      visual inspection, Sudan red test, pH measurement, and lipid droplet size
      distribution. Chemical stability for compartment A was evaluated by quantitative
      analyses of non-esterified fatty acids and peroxide content. The glucose-amino
      acid-electrolyte compartment B was evaluated physically by visual inspection,
      measuring particle contamination and pH. Chemical stability was assessed by
      discoloration, quantitative analyses of glucose, and the amino acids L-cysteine,
      L-tyrosine, and L-tryptophan. RESULTS: No phase separation or coalescence
      occurred, and the mean droplet size diameter did not exceed 0.5 um. Peroxide
      content and non-esterified fatty acids concentration of compartment A remained
      well below the limit of acceptation. No precipitation was detected for
      compartment B; only a slight yellow discoloration was noted at 80 d.
      Concentrations of glucose, L-tyrosine, and L-tryptophan remained stable; only L
      cysteine decreased significantly from its initial concentration. CONCLUSION: The
      two-compartment PED1 and PED1+E admixtures are stable up to 80 d 2 degrees  to 8
      degrees C + 24 h room temperature (RT) with an additional 7 d 2 degrees  to 8
      degrees C + 48 h RT after mixing and addition of vitamins and trace elements.

PMID- 29571609
TI  - Assessment of parenteral nutrition prescription in Canadian acute care settings.
AB  - BACKGROUND: Parenteral nutrition (PN) prescription can be challenging in patients
      with complex conditions and has potential complications. OBJECTIVE: To assess PN
      prescription, monitoring, and PN-related complications in a Canadian acute care
      setting. METHODS: This was a prospective cohort study in which patients receiving
      PN were assessed by an auditor for nutritional status, PN-related prescription,
      monitoring, and complications. In addition, length of stay and mortality were
      recorded. RESULTS: 147 patients (mean +/- SD 56.1 +/- 16.4 y) with complex
      diseases (Charlson comorbidity index, median [p25-p75] 2 [1-4]) were enrolled.
      Before starting PN, 18.6%, 63.9%, and 17.5% of patients were classified as
      subjective global assessment A, B, and C, respectively. Body mass index remained
      unchanged during the period on PN. On average, 89% and 73% of patients received
      <90% of their energy and protein requirements, respectively, but 65% received
      oral or enteral nutrition at some point during PN. The average daily energy
      provided by PN increased and stabilized on day 10, reaching 87.2 +/- 20.1% of the
      requirements. Line sepsis (6.8% of patients) and hyperglycemia (6.9%) were the
      most common complications. The overall mortality was 15.6%. For those alive,
      length of stay was 30 (range: 4-268) d. PN was discontinued because of
      transitioning to an oral diet (56.6%), enteral nutrition (17.6%), home PN
      (14.7%), palliative care (5.1%), death (4.4%), or other (1.5%). CONCLUSION: Most
      patients were malnourished at the start of PN. Energy and protein provided from
      PN were less than requirements, and the goals were reached with delay. Mortality
      was high, possibly as a result of complex diseases.

PMID- 29571610
TI  - Remodeling of the abdominal epithelial monolayer during the larva-pupa-adult
      transformation of Manduca.
AB  - During metamorphosis of insect epithelial monolayers, cells die, divide, and
      rearrange. In Drosophila undifferentiated diploid cells destined to form the
      adult cuticle of each abdominal segment segregate early in development from the
      surrounding polyploid larval epithelial cells of that segment as eight groups of
      diploid histoblast cells. The larval polyploid cells are programmed to die and be
      replaced by divisions and rearrangements of histoblast cells. By contrast,
      abdominal epithelial cells of Manduca larvae form a monolayer of cells
      representing different ploidy levels with no definitive segregation of diploid
      cells destined to form adult structures. These epithelial cells of mixed ploidy
      levels produce a thick smooth larval cuticle with sparsely distributed sensory
      bristles. Adult descendants of this larval monolayer produce a thinner cuticle
      with densely packed scale cells. The transition between these differentiated
      states of Manduca involves divisions of cells, changes in ploidy levels, and
      sorting of certain polyploid cells into circular rosette patches to minimize
      contacts of these polyploid cells with surrounding cells of equal or smaller
      size. Cells within the rosettes and some surrounding cells are destined to die
      and be replaced by remaining epithelial cells of uniform size and ploidy at pupa
      adult apolysis.

PMID- 29571611
TI  - JAK/STAT signaling prevents excessive apoptosis to ensure maintenance of the
      interfollicular stalk critical for Drosophila oogenesis.
AB  - Apoptosis not only eliminates cells that are damaged or dangerous but also cells
      whose function during development in patterning or organogenesis is complete. The
      successful formation of germ cells is essential for the perpetuation of a
      species. The production of an oocyte often depends on signaling between germline
      and somatic cells, but also between specialized types of somatic cells. In
      Drosophila, each developing egg chamber is separated from the next by a single
      file of interfollicular somatic cells. Little is known about the function of the
      interfollicular stalk, although its presumed role in separating egg chambers is
      to ensure that patterning cues from one egg chamber do not impact or disrupt the
      development of adjacent egg chambers. We found that cells comprising the stalk
      undergo a progressive decrease in number during oogenesis through an apoptotic
      dependent loss. The extent of programmed cell death is restricted by JAK/STAT
      signaling in a cell-autonomous manner to ensure that the stalk is maintained.
      Both a failure to undergo the normal reduction in stalk cell number, or to
      prevent excessive stalk cell apoptosis results in a decrease in fecundity. Thus,
      activation of JAK/STAT signaling in the Drosophila interfollicular stalk emerges
      as a model to study the tight regulation of signaling-dependent apoptosis.

PMID- 29571612
TI  - Kir2.1 is important for efficient BMP signaling in mammalian face development.
AB  - Mutations that disrupt the inwardly rectifying potassium channel Kir2.1 lead to
      Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmia,
      cognitive deficits, craniofacial dysmorphologies and limb defects. The molecular
      mechanism that underlies the developmental consequences of inhibition of these
      channels has remained a mystery. We show that while loss of Kir2.1 function does
      not affect expression of several early facial patterning genes, the domain in
      which Pou3f3 is expressed in the maxillary arch is reduced. Pou3f3 is important
      for development of the jugal and squamosal bones. The reduced expression domain
      of Pou3f3 is consistent with the reduction in the size of the squamosal and jugal
      bones in Kcnj2KO/KO animals, however it does not account for the diverse
      craniofacial defects observed in Kcnj2KO/KO animals. We show that Kir2.1 function
      is required in the cranial neural crest for morphogenesis of several craniofacial
      structures including palate closure. We find that while the palatal shelves of
      Kir2.1-null embryos elevate properly, they are reduced in size due to decreased
      proliferation of the palatal mesenchyme. While we find no reduction in expression
      of BMP ligands, receptors, and associated Smads in this setting, loss of Kir2.1
      reduces the efficacy of BMP signaling as shown by the reduction of phosphorylated
      Smad 1/5/8 and reduced expression of BMP targets Smad6 and Satb2.

PMID- 29571614
TI  - Coupling the roles of Hox genes to regulatory networks patterning cranial neural
      crest.
AB  - The neural crest is a transient population of cells that forms within the
      developing central nervous system and migrates away to generate a wide range of
      derivatives throughout the body during vertebrate embryogenesis. These cells are
      of evolutionary and clinical interest, constituting a key defining trait in the
      evolution of vertebrates and alterations in their development are implicated in a
      high proportion of birth defects and craniofacial abnormalities. In the hindbrain
      and the adjacent cranial neural crest cells (cNCCs), nested domains of Hox gene
      expression provide a combinatorial'Hox-code' for specifying regional properties
      in the developing head. Hox genes have been shown to play important roles at
      multiple stages in cNCC development, including specification, migration, and
      differentiation. However, relatively little is known about the underlying gene
      regulatory mechanisms involved, both upstream and downstream of Hox genes.
      Furthermore, it is still an open question as to how the genes of the neural crest
      GRN are linked to Hox-dependent pathways. In this review, we describe Hox gene
      expression, function and regulation in cNCCs with a view to integrating these
      genes within the emerging gene regulatory network for cNCC development. We
      highlight early roles for Hox1 genes in cNCC specification, proposing that this
      may be achieved, in part, by regulation of the balance between pluripotency and
      differentiation in precursor cells within the neuro-epithelium. We then describe
      what is known about the regulation of Hox gene expression in cNCCs and discuss
      this from the perspective of early vertebrate evolution.

PMID- 29571616
TI  - Laparoscopy-assisted versus open and pure laparoscopic approach for liver
      resection and living donor hepatectomy: a systematic review and meta-analysis.
AB  - BACKGROUND: Laparoscopy-assisted (hybrid) liver surgery is considered a minimally
      invasive technique, however there are doubts regarding loss of the benefits of
      laparoscopy due to the use of an auxiliary incision. The aim of this study was to
      compare perioperative results of hybrid vs. open and hybrid vs. pure laparoscopic
      approach to liver resection for focal lesions and living donation. METHODS: A
      systematic review was performed in Medline, EMBASE, Cochrane Library Central and
      LILACS databases. Perioperative outcomes were analyzed. RESULTS: 21 studies were
      included. Hybrid vs. open: operative time was lower in open group (mean
      difference [MD] = 34 min; 95%CI: 22-47; P < 0.001; N = 669). Hybrid technique was
      associated with a reduction in operative blood loss [MD = -43 ml; 95%CI: -74-(
      13); P = 0.005, N = 1738]; shorter hospital stay [MD = -1.9 days; 95%CI: -3.2-(
      0.5); P = 0.008; N = 833] and lower morbidity [risk difference (RD) = -0.05;
      95%CI: -0.10-(-0.01); P = 0.010; N = 1359]. Hybrid vs. pure laparoscopic: There
      was no difference regarding blood loss, transfusion rate, hospital stay and
      morbimortality. DISCUSSION: Hybrid technique had perioperative outcomes that were
      more in keeping with pure laparoscopic outcomes than open surgery. Hybrid liver
      surgery should be considered a minimally invasive approach.

PMID- 29571613
TI  - Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest
      level of vertebrate Hedgehog response.
AB  - Smoothened (Smo) is the essential transducer of Sonic hedgehog (Shh) signaling,
      which regulates cell fate and proliferation during embryogenesis. We identified a
      novel mouse mutant, cabbie (cbb), and found that its cause is a missense mutation
      in Smo. We showed the Smocbb mutation is insensitive to the Shh agonist SAG,
      perhaps due to the disruption of SAG binding. We characterized Smocbb for defects
      in craniofacial and skeletal development, as well as neural tube patterning, and
      revealed Smocbb affected processes that require the highest levels of Shh
      activity. Smo is normally enriched in cilia upon Shh stimulation; however, we
      detected inefficient enrichment of Smo in Smocbb mutants whether we stimulated
      with Shh or SAG. Taken together, our data suggest that the highest levels of
      vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment.

PMID- 29571615
TI  - Variation in hospital mortality after pancreatoduodenectomy is related to failure
      to rescue rather than major complications: a nationwide audit.
AB  - BACKGROUND: In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of
      major complications and Failure to Rescue (FTR) after pancreatoduodenectomy
      between low- and high-mortality hospitals are compared, and independent
      predictors for FTR investigated. METHODS: Patients undergoing
      pancreatoduodenectomy in 2014 and 2015 in The Netherlands were included.
      Hospitals were divided into quartiles based on mortality rates. The rate of major
      complications (Clavien-Dindo >=3) and death after a major complication (FTR) were
      compared between these quartiles. Independent predictors for FTR were identified
      by multivariable logistic regression analysis. RESULTS: Out of 1.342 patients,
      391 (29%) developed a major complication and in-hospital mortality was 4.2%. FTR
      occurred in 56 (14.3%) patients. Mortality was 0.9% in the first hospital
      quartile (4 hospitals, 327 patients) and 8.1% in the fourth quartile (5
      hospitals, 310 patients). The rate of major complications increased by 40% (25.7%
      vs 35.2%) between the first and fourth hospital quartile, whereas the FTR rate
      increased by 560% (3.6% vs 22.9%). Independent predictors of FTR were male sex
      (OR = 2.1, 95%CI 1.2-3.9), age >75 years (OR = 4.3, 1.8-10.2), BMI >=30 (OR =
      2.9, 1.3-6.6), histopathological diagnosis of periampullary cancer (OR = 2.0, 1.1
      3.7), and hospital volume <30 (OR = 3.9, 1.6-9.6). CONCLUSIONS: Variations in
      mortality between hospitals after pancreatoduodenectomy were explained mainly by
      differences in FTR, rather than the incidence of major complications.

PMID- 29571617
TI  - Alcohol injection into the portal vein prior to ligation increases liver
      regeneration rate.
AB  - BACKGROUND: Failure of portal vein ligation (PVL) to induce hypertrophy is not
      uncommon. The aim of the study was to evaluate the impact of intraportal alcohol
      injection prior to ligation on liver regeneration. METHOD: Forty-two patients
      with colorectal liver metastases who underwent PVL between 01/2004 and 06/2014
      were analyzed. Beginning in 09/2011, alcohol was injected prior to PVL. Patients
      treated with PVL alone (Alc- group) were compared with those treated with alcohol
      injection plus PVL (Alc+ group). Liver regeneration was assessed by volumetric
      increase (VI). RESULTS: Alc+ (23 patients) and Alc- (19 patients) groups were
      similar in terms of age, sex and pre-PVL FLRV. Alc- group had a higher risk of
      recanalization (12 vs. 1, p < 0.001) and cavernous transformation (7 vs. 2, p =
      0.055) of the occluded portal vein. Post-PVL FLRV (43.3 +/- 14.3% vs. 34.6 +/-
      6.4%, p = 0.013) and VI (0.44 +/- 0.24 vs. 0.28 +/- 0.20, p = 0.029) were higher
      in Alc+ group. On multivariate analysis male sex (B = -0.149) and alcohol
      injection (B = 0.143) significantly predicted VI. CONCLUSIONS: Alcohol injection
      prior to PVL may increase the regeneration of the FLRV by reducing the
      recanalization of the occluded portal vein.

PMID- 29571618
TI  - Insight on ALPPS - Associating Liver Partition and Portal Vein Ligation for
      Staged Hepatectomy - mechanisms: activation of mTOR pathway.
AB  - BACKGROUND: ALPPS procedure has been introduced to increase the volume of future
      liver remnant. The mechanisms underlying the accelerated regeneration observed
      with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an
      integrating pathway for metabolic signals leading to proliferation and cell
      growth. Our aim was to analyze increase in liver volume, proliferation parameters
      and expression of AMPK/mTOR pathway-related molecules in patients undergoing
      ALPPS. METHODS: A single center prospective study of patients undergoing ALPPS
      was performed from 2013 to 2015. Liver and serum samples, clinical laboratory
      results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR
      were performed in deportalized and remnant liver tissue in both stages of the
      procedure. RESULTS: 11 patients were enrolled. Remnant liver volume increased 112
      +/- 63% (p < 0.05) in 9.1 +/- 1.6 days. Proliferation-related cytokines IL-6, TNF
      alpha, HGF and EGF significantly increased, while higher Ki-67 immunostaining and
      cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E
      BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at
      second stage, while AMPK and Akt increased only in deportalized liver samples.
      CONCLUSION: Rapid liver regeneration with ALPPS might be associated with
      hepatocyte proliferation induced by mTOR pathway activation.

PMID- 29571619
TI  - Predictive factors of recurrent endovascular intervention for cephalic arch
      stenosis after percutaneous transluminal angioplasty.
AB  - OBJECTIVE: Cephalic arch stenosis (CAS) is an important and recurring problem
      arising in hemodialysis patients because of the requirement for repeated
      interventions to maintain patency. The aim of this study was to determine
      predictive factors for recurrence of CAS after successful angioplasty. METHODS: A
      retrospective, case-control study was conducted at two ambulatory vascular access
      (VA) centers. All patients with a dysfunctional VA referred for an angiographic
      procedure and with a documented CAS as evidenced during the endovascular
      intervention (EI) between January 1, 2013, and December 31, 2015, were enrolled;
      15 patients in whom an efficacious intervention was not possible were excluded.
      The study thus concerned 375 EIs using percutaneous transluminal angioplasty
      without stent placement on 241 VAs for CAS (9% of all procedures performed)
      during a 3-year period. Patients were compared regarding the absence (group 1; n
      = 181) or presence (group 2; n = 60) of recurrent CAS. We defined recurrence as
      that which occurred within 180 days of the previous successful EI for CAS. Any
      CAS diagnosed and treated >180 days after a previous one was considered a novel
      CAS and not a recurrence. Multivariate analysis was performed to determine
      variables independently associated with recurrence of CAS. Kaplan-Meier analysis
      was performed for determination of primary and assisted primary patency in this
      population. RESULTS: The recurrence rate of CAS was high (25%). Patients in both
      groups had similar demographic characteristics, time on hemodialysis, and mean
      dialysis dose and access flow rate at referral (P > .05). Multivariate analysis
      provided a significant discriminatory influence pertaining to diabetes (hazard
      ratio [HR], 2.054; 95% confidence interval [CI], 1.22-3.46; P = .007), residual
      stenosis even though it was <30% (HR, 1.86; 95% CI, 1.005-3.439; P = .048), and
      the finding of an isolated CAS lesion (HR, 0.445; 95% CI, 0.219-0.905; P = .025)
      in comparing group 1 and group 2. All other variables lost statistical
      significance on multivariate analysis. Primary patency at 6 months was 72%,
      increasing to an assisted primary patency of 89% at 6 months. The median
      durations of primary patency and assisted primary patency were 9.5 months and
      15.6 months, respectively. CONCLUSIONS: Multivariate analysis showed that
      diabetes and residual stenosis (albeit <30%) were predictive of recurrence,
      whereas the finding of an isolated CAS lesion as opposed to stenoses in multiple
      locations was shown to be negatively associated with recurrent CAS, appearing to
      be "protective".

PMID- 29571620
TI  - Regional variation in patient outcomes in carotid artery disease treatment in the
      Vascular Quality Initiative.
AB  - OBJECTIVE: Quality metrics were developed to improve outcomes after carotid
      artery revascularization; however, few studies have evaluated regional
      differences in perioperative outcomes. This study aimed to evaluate regional
      variation in mortality and perioperative outcomes after carotid endarterectomy
      (CEA) and carotid artery stenting (CAS). METHODS: We identified all patients who
      underwent CEA or CAS from 2009 to 2016 in the Vascular Quality Initiative.
      Patients were analyzed on the basis of their symptom status. We assessed
      variation in perioperative outcomes using chi2 analysis, Fisher exact test, and t
      test, where appropriate. RESULTS: A total of 78,467 carotid interventions were
      identified; 85% were CEAs, with 69% of those asymptomatic. Within CAS, 39% were
      asymptomatic. Perioperative stroke/death varied across regions within both CAS
      groups (asymptomatic, 0%-5.8% [P = .03]; symptomatic, 2.4%-8.1% [P = .1]), and
      several regions did not meet the American Heart Association (AHA) guidelines of
      3% for asymptomatic patients and 6% for symptomatic patients, which persisted
      after risk adjustment. For CEA, the stroke/death rates fell within the standards
      set by the AHA guidelines in all regions for both the unadjusted and risk
      adjusted models; however, there was significant regional variation in the cohorts
      (asymptomatic, 0.9%-3.1% [P < .01]; symptomatic, 1.3%-4.9% [P < .01]). Variation
      in 30-day mortality was significant in symptomatic patients (asymptomatic: CEA,
      0%-1.3% [P = .2], CAS, 0%-2.4% [P = .2]; symptomatic: CEA, 0%-1.8% [P < .01],
      CAS, 0%-4.6% [P = .01]). Rates of in-hospital stroke, postoperative myocardial
      infarction, prolonged length of stay (>2 days), and use of intravenous blood
      pressure medications all varied significantly across the regions. After CEA,
      there was significant variation in the rates of cranial nerve injuries
      (asymptomatic, 0.9%-4.9% [P < .01]; symptomatic, 1.5%-7.7% [P < .01]), return to
      the operating room (asymptomatic, 0.9%-3.4% [P < .01]; symptomatic, 0.6%-3.4% [P
      = .02]), and discharge on antiplatelet and statin (asymptomatic, 75%-87% [P <
      .01]; symptomatic, 78%-91% [P < .01]). After CAS, significant variation was found
      in the rates of access site complications (asymptomatic, 2.3%-18.2% [P < .01];
      symptomatic, 1.4%-16.9% [P < .01]) and discharge on dual antiplatelet therapy
      (asymptomatic, 79%-94% [P < .01]; symptomatic, 83%-93% [P < .01]). CONCLUSIONS:
      Unwarranted regional variation exists in outcomes after carotid artery
      revascularization across the regions of the VQI. Significant variation was seen
      in a number of outcomes for which quality metrics currently exist, such as length
      of stay and discharge medications. In addition, after CAS, several regions failed
      to meet the AHA guidelines for stroke and death. Given these results, quality
      improvement projects should be targeted to improve adherence to current
      guidelines to promote best practices.

PMID- 29571621
TI  - Comparing the efficacy of shunting approaches and cerebral monitoring during
      carotid endarterectomy using a national database.
AB  - OBJECTIVE: Carotid endarterectomy practice patterns, including the use of shunts
      and cerebral monitoring techniques, are typically surgeon-dependent and differ
      greatly on a national level. Prior literature evaluating these techniques is
      often underpowered for detecting variations in low-frequency outcomes. The
      purpose of this study was to evaluate current carotid endarterectomy practice
      patterns and to allow comparison across surgical approaches using a large
      national database. METHODS: We divided carotid cases entered into the Vascular
      Quality Initiative database between October 2012 and April 2015 into routine
      shunting, selective shunting, and never shunting cohorts, excluding
      endarterectomies performed with concomitant procedures and those with incomplete
      information on the use of a shunt. The selective group was subdivided into cases
      with awake, electroencephalography, and stump pressure monitoring. We evaluated
      differences in practice patterns and compared rates of stroke, death, return to
      the operating room, reperfusion injury, and re-exploration after closure across
      these groups. Multivariate logistic regression models adjusting for risk factors
      were used to identify predictors of each outcome. RESULTS: Between October 2012
      and April 2015, there were a total of 28,457 endarterectomies included in our
      analysis, of which 14,128 involved routine shunting, 1740 involved never
      shunting, and 12,489 involved selective shunting. Of the selective cases, 6144
      involved electroencephalography monitoring, 2310 involved stump pressure
      monitoring, and 2052 involved awake monitoring. Unadjusted rates of in-hospital
      death and stroke were 0.30% (95% confidence interval [CI], 0.21-0.39) and 0.78%
      (95% CI, 0.64-0.93) for routine shunting and 0.22% (95% CI, 0.14-0.31) and 0.91%
      (95% CI, 0.75-1.08) for selective shunting, respectively. The unadjusted rate of
      in-hospital death was lower in the awake monitoring group than in the routine
      shunting group (0.05% vs 0.30%; P = .037). After adjustment for patient risk
      factors, the multivariate models showed no difference in rates of any primary
      outcomes among the groups, although there was a shorter postoperative length of
      stay for the awake monitoring group compared with the routine shunting group
      (1.55 days vs 2.00 days, respectively; P < .01). CONCLUSIONS: Analysis of the
      Vascular Quality Initiative registry shows equivalent unadjusted rates of in
      hospital death and stroke across different approaches to shunting and cerebral
      monitoring with the exception of the awake monitoring group, which has lower
      unadjusted mortality compared with the routine shunting group. In the risk
      adjusted analysis, however, there are no differences across any of the groups.
      Given the clinical equivalence of approaches to shunting and cerebral monitoring,
      further work should evaluate the relative cost of these techniques.

PMID- 29571622
TI  - Comparison between activated clotting time and anti-activated factor X activity
      for the monitoring of unfractionated heparin therapy in patients with aortic
      aneurysm undergoing an endovascular procedure.
AB  - OBJECTIVE: Current guidelines recommend administration of unfractionated heparin
      (UFH) and measurement of activated clotting time (ACT) during endovascular
      procedures. The aim of this study was to compare ACT and anti-activated factor X
      (anti-Xa) measurements for monitoring of UFH therapy during an aortic endograft
      procedure and to assess the association of peak ACT and peak anti-Xa activity
      with periprocedural bleeding. METHODS: We retrospectively studied 104 patients
      with aortic aneurysm undergoing endovascular procedures with repeated coagulation
      measurements. After a UFH bolus, further UFH doses were given according to ACT
      (target range, >=250 seconds) in clinical routine, and in parallel to each ACT
      (Hemochron; Accriva Diagnostics, Newport Beach, Calif) measurement, we determined
      anti-Xa activity (HemosIL Liquid anti-Xa; Instrumentation Laboratory, Bedford,
      Mass). UFH redosing was solely based on the ACT measurements. We defined
      periprocedural bleeding as a drop in hemoglobin level >=3 g/dL or red blood cell
      transfusion within 24 hours. RESULTS: After the initial UFH bolus (median, 67
      IU/kg body weight), ACT and anti-Xa measurements showed a weak correlation (rs,
      0.46; P < .001). Median ACT was 233 seconds (range, 127-374 seconds;
      interquartile range [IQR], 204-257 seconds); median anti-Xa activity was 1.0
      IU/mL (range, 0.5-2.0 IU/mL; IQR, 0.9-1.2 IU/mL). Only 31% of the patients had an
      ACT value >=250 seconds, whereas all patients had an anti-Xa activity >=0.5
      IU/mL. Accordingly, ACT triggered redosing of UFH frequently. Consequently, we
      saw a median total UFH use of 90 IU/kg during the procedure, a median peak ACT of
      255 seconds (IQR, 234-273 seconds), and a median peak anti-Xa activity of 1.2
      IU/mL (IQR, 1.0-1.4 IU/mL). Periprocedural bleeding occurred in 40 (38%)
      patients. Peak ACT >=250 seconds was not associated with bleeding (odds ratio,
      1.05; 95% confidence interval, 0.41-2.70; P = .952), whereas peak anti-Xa
      activity >=1.2 IU/mL was independently associated with bleeding (odds ratio,
      4.95; 95% confidence interval, 1.82-13.48; P = .002). Moreover, no periprocedural
      thromboembolic event occurred. CONCLUSIONS: In this retrospective study of
      patients with aortic aneurysm undergoing an endovascular procedure, ACT and anti
      Xa measurements showed poor correlation; only increased peak anti-Xa activity was
      independently associated with periprocedural bleeding, not increased ACT. Our
      findings also suggest that monitoring of UFH therapy with anti-Xa during aortic
      endograft procedures may reduce total UFH use. We further speculate that this
      approach could reduce periprocedural bleeding.

PMID- 29571623
TI  - Real-world evidence of superiority of endovascular repair in treating ruptured
      abdominal aortic aneurysm.
AB  - OBJECTIVE: The majority of previous studies, including randomized controlled
      trials, have failed to provide sufficient evidence of superiority of endovascular
      aneurysm repair (EVAR) over open aortic repair (OAR) of ruptured abdominal aortic
      aneurysm (rAAA) while comparing mortality and complications. This is in part due
      to small study size, patient selection bias, scarce adjustment for essential
      variables, single insurance type, or selection of only older patients. This study
      aimed to provide real-world, contemporary, comprehensive, and robust evidence on
      mortality of EVAR vs OAR of rAAA. METHODS: A retrospective observational cohort
      study was performed of rAAA patients registered in the Premier Healthcare
      Database between July 2009 and March 2015. A multivariate logistic regression
      model was operated to estimate the association between procedure types (OAR vs
      EVAR) and in-hospital mortality. The final model was adjusted for demographics
      (age, sex, race, marital status, and geographic region), hospital characteristics
      (urban or rural, teaching or not), and potential confounders (hypertension,
      diabetes, hypercholesterolemia, obesity, ischemic heart disease, chronic kidney
      disease, symptoms of critical limb ischemia, chronic obstructive pulmonary
      disease, smoking, and alcoholism). Furthermore, coarsened exact matching was
      applied to substantiate the result in the matched cohort. RESULTS: There were a
      total of 3164 patients with rAAA (1550 [49.0%] OAR and 1614 [51.0%] EVAR).
      Mortality was 23.79% in the EVAR group compared with 36.26% in the OAR group (P <
      .001). The adjusted odds ratios of mortality (1.91; 95% confidence interval [CI],
      1.62-2.25; P < .001), cardiac complication (1.54; 95% CI, 1.22-1.96; P < .001),
      pulmonary failure (1.90; 95% CI, 1.60-2.24; P < .001), renal failure (1.90; 95%
      CI, 1.61-2.23; P < .001), and bowel ischemia (2.40; 95% CI, 1.70-3.35; P < .001)
      were significantly higher after OAR compared with EVAR. We further applied
      coarsened exact matching, which followed the same pattern of mortality (odds
      ratio, 1.68; 95% CI 1.41-1.99; P < .001) and all major complications.
      CONCLUSIONS: Although the choice of repair of rAAA is highly dependent on the
      experience of the operating team and the anatomic suitability of the patient,
      this contemporary analysis of a large cohort of rAAA showed significantly higher
      adjusted risk of mortality in OAR compared with EVAR and substantially higher
      complications.

PMID- 29571624
TI  - Tissue factor levels and the fibrinolytic system in thin and thick intraluminal
      thrombus and underlying walls of abdominal aortic aneurysms.
AB  - BACKGROUND: The hemostatic system cooperates with proteolytic degradation in
      processes allowing abdominal aortic aneurysm (AAA) formation. In previous
      studies, it has been suggested that aneurysm rupture depends on intraluminal
      thrombus (ILT) thickness, which varies across each individual aneurysm. We
      hypothesized that hemostatic components differentially accumulate in AAA tissue
      in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and
      aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one
      aneurysm sac were taken from 35 patients undergoing elective repair. METHODS:
      Factor levels were measured using enzyme-linked immunosorbent assay of protein
      extract. RESULTS: Tissue factor (TF) activities were significantly higher in
      thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001;
      B vs B1, P = .001). Significantly higher tissue plasminogen activator was found
      in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P <
      .001, and P < .001, respectively). Plasminogen concentrations were highest in
      ILT. Concentrations of alpha2-antiplasmin in thin ILT adjacent walls (B) were
      higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1;
      P < .001). Significant correlations between levels of different factors were
      mostly found in thick ILT (A1). However, no correlations were found at B sites,
      except for a correlation between plasmin and TF activities (r = 0.55; P = .004).
      CONCLUSIONS: These results suggest that higher TF activities are present in
      thinner AAA regions. These parameters and local fibrinolysis may be part of the
      processes leading to destruction of the aneurysm wall.

PMID- 29571625
TI  - Preoperative mapping of the aortoiliac territory with duplex ultrasound in
      patients with peripheral arterial occlusive disease.
AB  - OBJECTIVE: Duplex ultrasound (DUS) arterial mapping of the aortoiliac area is
      limited by obesity, abdominal gas, and the need to use a low-frequency probe (and
      therefore poorer resolution) in the examination. The aim of this study was to
      analyze the degree of agreement between DUS mapping of the aortoiliac area and
      angiography or contrast-enhanced computed tomography angiography (CTA). METHODS:
      This was a retrospective observational study. Between November 2006 and June
      2015, there were 173 patients with a surgical indication for aortoiliac occlusive
      disease included, with preoperative aortoiliac DUS mapping and subsequent CTA or
      intraoperative angiography. Sensitivity, specificity, positive predictive value,
      and negative predictive value of DUS as an arterial mapping test were analyzed,
      as was the degree of agreement with angiography/CTA and agreement between the
      surgical indication based on DUS and the final surgical technique performed.
      RESULTS: Of 173 DUS mapping tests, 155 were evaluated (89.6%); the remaining 18
      were not able to be evaluated because of the patient's obesity or bowel gas.
      Overall accuracy of DUS for predicting significant artery lesions was as follows:
      92% sensitivity (95% confidence interval [CI], 88%-95%), 96% specificity (95% CI,
      95%-97%), 89% positive predictive value (95% CI, 86%-93%), and 97% negative
      predictive value (95% CI, 96%-98%). Agreement with angiography/CTA had a kappa
      index of 0.81 (95% CI, 0.77-0.84), which reflects a good degree of agreement.
      Surgical indications based on DUS mapping were correct in 89% of cases (138/155).
      CONCLUSIONS: DUS mapping of the aortoiliac territory could be used as a single
      preoperative imaging test in aortoiliac occlusive disease in patients whose DUS
      examination is able to be evaluated.

PMID- 29571626
TI  - A systematic review and meta-analysis of endovascular versus open surgical
      revascularization for chronic mesenteric ischemia.
AB  - BACKGROUND: Despite the enthusiasm for endovascular revascularization for chronic
      mesenteric ischemia (CMI), it is not clear if early benefits offset long-term
      patency rates. This systematic review aimed to provide an up-to-date
      comprehensive evidence synthesis evaluating the two approaches. METHODS: We
      searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials,
      Cochrane Database of Systematic Reviews, and Scopus through July 15, 2016, for
      studies that compared the endovascular with the open surgical approach for
      revascularization in CMI patients. We conducted a random-effects meta-analysis to
      pool outcomes of interest across studies. RESULTS: We included 100 observational
      studies (22 comparative, 78 noncomparative; 18,726 patients; mean age, 69 years).
      Open surgery was associated with a statistically significant increase in the risk
      of in-hospital complications (relative risk [RR], 2.2; 95% confidence interval
      [CI], 1.8-2.6) and a nonsignificant increase in mortality at 30 days (RR, 1.57;
      95% CI, 0.84-2.93). Open surgery was associated with lower risk of 3-year
      recurrence rates (RR, 0.47; 95% CI, 0.34-0.66) and a similar 3-year survival.
      Data from noncomparative studies provided similar inferences. The quality of
      evidence was low. CONCLUSIONS: Observational evidence suggests that the
      endovascular approach for revascularization in patients with CMI may offer better
      early outcomes than open surgery, although this effect may not be durable. Long
      term mortality appears to be similar.

PMID- 29571627
TI  - Long-term decline in renal function is more significant after endovascular repair
      of infrarenal abdominal aortic aneurysms.
AB  - OBJECTIVE: It is not clear whether endovascular aneurysm repair (EVAR) of
      abdominal aortic aneurysms (AAAs) results in an increase in renal insufficiency
      during the long term compared with open repair (OR). We reviewed our experience
      with AAA repair to determine whether there was a significant difference in
      postoperative and long-term renal outcomes between OR and EVAR. METHODS: A
      retrospective cohort study was conducted of all patients who underwent AAA repair
      between January 1993 and July 2013 at a tertiary referral hospital. Demographics,
      comorbidities, preoperative and postoperative laboratory values, morbidity, and
      mortality were collected. Patients with ruptured AAAs, preoperative hemodialysis,
      juxtarenal or suprarenal aneurysm origin, and no follow-up laboratory values were
      excluded. Preoperative, postoperative, 6-month, and yearly serum creatinine
      values were collected. Glomerular filtration rate (GFR) was calculated on the
      basis of the Chronic Kidney Disease Epidemiology Collaboration equation. Acute
      kidney injury (AKI) was classified using the Kidney Disease: Improving Global
      Outcomes guidelines. Change in GFR was defined as preoperative GFR minus the GFR
      at each follow-up interval. Comparison was made between EVAR and OR groups using
      multivariate logistics for categorical data and linear regression for continuous
      variables. RESULTS: During the study period, 763 infrarenal AAA repairs were
      performed at our institution; 675 repairs fit the inclusion criteria (317 ORs and
      358 EVARs). Mean age was 73.9 years. Seventy-nine percent were male, 78% were
      hypertensive, 18% were diabetic, and 31% had preoperative renal dysfunction
      defined as GFR below 60 mL/min. Using a multivariate logistic model to control
      for all variables, OR was found to have a 1.6 times greater chance for
      development of immediate postoperative AKI compared with EVAR (P = .038).
      Hypertension and aneurysm size were independent risk factors for development of
      AKI (P = .012 and .022, respectively). Using a linear regression model to look at
      GFR decline during several years, there was a greater decline in GFR in the EVAR
      group. This became significant starting at postoperative year 4. AKI and
      preoperative renal dysfunction were independent risk factors for long-term
      decline in renal function. CONCLUSIONS: Although AKI is less likely to occur
      after EVAR, patients undergoing EVAR experience a significant but delayed decline
      in GFR over time compared with OR. This became apparent after postoperative year
      4. Studies comparing EVAR and OR may need longer follow-up to detect clinically
      significant differences in renal function.

PMID- 29571628
TI  - Differences in alpha-Crystallin isomerization reveal the activity of protein
      isoaspartyl methyltransferase (PIMT) in the nucleus and cortex of human lenses.
AB  - Although it is well-known that protein turnover essentially stops in mature lens
      fiber cells, mapping out the ensuing protein degradation and its effects on lens
      function over time remains challenging. In particular, isomerization is a common,
      spontaneous post-translational modification that occurs over long timescales and
      generates products invisible to most analytical methods. Nevertheless,
      isomerization can significantly impact protein structure, function, and
      solubility, which are all necessary to maintain clarity and proper refractive
      index within the lens. Herein, we examine the degree of isomerization occurring
      in crystallin proteins in the human eye lens as a function of both age and
      location within the lens. A novel mass spectrometric technique leveraging radical
      chemistry enables detailed characterization of proteins extracted from the cortex
      and nucleus of the lens. It is observed that the degree of isomerization
      increases significantly between the cortex and nucleus and between water-soluble
      and water-insoluble fractions. Interestingly, the abundance of L-isoAsp is low in
      the water-soluble cortex despite being the dominant product generated by
      isomerization of Asp in vitro, suggesting that Protein L-isoaspartyl
      methyltransferase (PIMT) is active in the cortex and suppresses the accumulation
      of L-isoAsp. The abundance of L-isoAsp increases dramatically in the nucleus,
      revealing that PIMT activity decreases over time in the center of the lens. In
      addition, the growth of L-isoAsp in the nuclear fraction suggests protein
      isomerization continues within the nucleus, despite the fact that most of the
      protein within the nucleus has become insoluble. Additionally, it is demonstrated
      that sequential Asp residues lead to isomerization hotspots in human crystallin
      proteins and that the isomerization profiles for alphaA and alphaB crystallin are
      notably different. Although alphaA is more prone to isomerization, alphaB loses
      solubility more rapidly upon modification. These differences are likely related
      to the distribution of Asp residues within alphaA and alphaB, which are in turn
      connected to refractive index. The high Asp content of alphaA is a hazard in
      terms of isomerization and aging, but it serves to enhance the refractive index
      of alphaA relative to alphaB, and may explain why alphaA is only found in the
      eye.

PMID- 29571629
TI  - Partial retinal photoreceptor loss in a transgenic mouse model associated with
      reduced levels of interphotoreceptor retinol binding protein (IRBP, RBP3).
AB  - Organ-specific transgenic membrane expression of hen egg lysozyme (HEL) as a "neo
      self antigen" has been used in several models to study immunological tolerance.
      In this study we report the changes which occur in the B10.BR mouse retina when
      membrane-bound HEL is expressed in photoreceptors under the control of the
      promoter for interphotoreceptor retinoid binding protein (IRBP, RBP3). On direct
      clinical examination of the single transgenic (sTg-IRBP:HEL) mouse fundus, a low
      level increase in retinal degeneration compared to non-transgenic controls was
      observed, presenting as drusenoid deposits and occasional small patches of
      atrophy. On histological examination, there was an overall shortening of outer
      segments and loss of photoreceptor nuclei in sTg-IRBP:HEL mice, which was more
      pronounced in the retinal periphery, particularly inferiorly. The fundoscopically
      observed lesions did not correlate with the photoreceptor shortening/loss but
      appeared to be located at the level of the retinal pigment
      epithelium/choriocapillaris layer and were an exaggeration in size and number of
      similar age-related changes found in wild type (WT) mice. In addition, neither
      the atrophic lesions nor the photoreceptor shortening were associated with common
      retinal degeneration genes, nor were they caused by exposure to light damage
      since mice housed at both high and low ambient light levels had similar degrees
      of retinal degeneration. Instead, sTg-IRBP:HEL mice expressed reduced levels of
      soluble retinal IRBP compared to WT mice which were present from postnatal day16
      (P16) and preceded development of photoreceptor shortening (onset P21). We
      propose that insertion of the HEL transgene in the photoreceptor membrane
      disrupted normal photoreceptor function and led to reduced levels of soluble IRBP
      and retinal thinning. A similar phenotype has been observed in IRBP deficient
      mice. Despite the retinal thinning, the amount of HEL expressed in the retina was
      sufficient to act as an autoantigenic target when the mice were crossed to the
      HEL T cell receptor Tg mouse, since double transgenic (dTg-IRBP:HEL) mice
      spontaneously developed a severe uveoretinitis with onset at weaning. We suggest
      that, although membrane expression of foreign transgene products is likely to
      modify the structure and function of tissues and cells, the technology provides
      useful models to investigate mechanisms of antigen-specific immunological
      tolerance.

PMID- 29571630
TI  - Short- and long-term freezing effects in a coastal (Lobaria virens) versus a
      widespread lichen (L. pulmonaria).
AB  - Lichens are considered freezing tolerant, although few species have been tested.
      Growth, a robust measure of fitness integrating processes in all partners of a
      lichen thallus, has not yet been used as a viability measure after freezing. We
      compared relative growth rates (RGR) after freezing with short-term viability
      measures of photo- and mycobiont functions in the coastal Lobaria virens and the
      widespread L. pulmonaria to test the hypothesis that low temperature shapes the
      coastal distribution of L. virens. Hydrated thalli from sympatric populations
      were subjected to freezing at -10, -20 and -40  degrees C for 5 h. The rate of
      cooling and subsequent warming was 5  degrees C h-1. Short-term viability
      measures of photobiont (maximal photosystem II efficiency, effective PSII yield)
      and mycobiont viability (conductivity index), as well as subsequent RGR, were
      assessed. The exotherms showed that L. virens froze at -3  degrees C; L.
      pulmonaria, at -4  degrees C. Freezing significantly impaired short-term
      viability measures of both photo- and mycobiont, particularly in the coastal
      species. Lobaria pulmonaria grew 2.1 times faster than L. virens, but the short
      term damage after one freezing event did not affect the long-term RGR in any
      species. Thereby, short-term responses were impaired by freezing, long-term
      responses were not. While the lacking RGR-responses to freezing suggest that
      freezing tolerance does not shape the coastal distribution of L. virens, the
      significant reported adverse short-term effects in L. virens may be aggravated by
      repeated freezing-thawing cycles in cold winters. In such a perspective, repeated
      freezing may eventually lead to reduced long-term fitness in L. virens.

PMID- 29571631
TI  - Vitrification of aortic valve homografts suppresses NLRP3 inflammasome activation
      and alleviates the inflammatory response after transplantation.

PMID- 29571632
TI  - Sperm kinematics and subpopulational responses during the cryopreservation
      process in caprine ejaculates.
AB  - Sperm cryopreservation in goats has been a challenge for many years due to the
      detrimental effects of seminal plasma enzymes produced by the bulbo-urethral
      glands which catalyse the hydrolysis of lecithins in egg yolk to fatty acids and
      lysolecithins which are deleterious to spermatozoa. This fact implies to carry
      out additional processing steps during sperm cryopreservation for seminal plasma
      removal triggering different sperm responses which may affect sperm
      functionality. The objective of the present study was to determine specific sperm
      subpopulation responses in different handling steps during the cryopreservation
      process by using functional sperm kinematic descriptors in caprine ejaculates.
      Buck ejaculates (n = 40) were analysed for sperm concentration, viability,
      morphology and acrosome integrity. Moreover, sperm motility was assessed using a
      computer-assisted sperm analysis (CASA) system after five different handling
      steps (fresh sperm, 1st washing, 2nd washing, cooling and frozen-thawed sperm)
      during a standard cryopreservation protocol for goat semen. The results were
      analysed using Principal Component Analysis (PCA) and multivariate clustering
      procedures to establish the relationship between the distribution of the
      subpopulations found and the functional sperm motility in each step. Except for
      the 1st and 4th steps, four sperm kinematic subpopulations were observed
      explaining more than 75% of the variance. Based on velocity and linearity
      parameters and the subpopulations disclosed, the kinematic response varies among
      processing steps modifying sperm movement trajectories in a subpopulation
      specific and handling step-dependent manner (p < 0.001). The predominant motile
      subpopulation in freshly ejaculated buck sperm had very fast velocity
      characteristics and a non-linear trajectory (41.1%). Washing buck sperm twice
      altered the subpopulation structure as well as cooling which resulted in a
      dramatic reduction in sperm velocities (p < 0.01). Frozen-thawed spermatozoa
      showed similar characteristics to cooled sperm except there was a further
      increase in linearity with a large proportion of sperm attributed to new slow,
      linear cluster (32.5%). In conclusion, this study confirms the variability and
      heterogeneity of goat sperm kinematic patterns throughout the cryopreservation
      process and suggests that the predominant motility pattern (assayed in vitro via
      CASA) of high quality spermatozoa might be typified by high speed and a non
      linear trajectory. The relationships among the number and distribution of sperm
      subpopulations and the different handling steps were particularlly relevant,
      specially after the cooling and the post-thawing steps, when effects derived from
      these critical handling steps were evident and altered drastically the sperm
      motion patterns.

PMID- 29571633
TI  - Technology-enabled population health.

PMID- 29571634
TI  - The effect of metabolic surgery on nonobese patients (BMI<30 kg/m2) with type 2
      diabetes: a systematic review.
AB  - BACKGROUND: The influence of metabolic surgery on the glucose and lipid profiles
      of nonobese body mass index<30 kg/m2 patients with type 2 diabetes, particularly
      the effect >=1 year, remains unknown. METHODS: PubMed and Ovid Embase were used.
      SETTING: University hospitals. RESULTS: In total, 21 studies including 921
      patients were examined in this systematic review, the results of which revealed
      decrease in body mass index, waist circumference, fasting plasma glucose,
      glycosylated hemoglobin A1C, fasting C-peptide, fasting insulin, homeostasis
      model of assessment for insulin resistance index, triglycerides, total
      cholesterol, and low-density lipoprotein cholesterol. An increase in high-density
      lipoprotein cholesterol was also observed. The diabetes remission rates ranged
      from 13.3% to 90.2% according to 20 studies. The incidence of gastrointestinal
      bleeding ranged from 1% to 10% according to 9 studies. Four studies reported
      anemia after Roux-en-Y gastric bypass or one-anastomosis gastric bypass, with the
      incidence ranging from 8% to 33%. CONCLUSIONS: Nonobese patients can achieve
      improvements in weight-related indices and glucose and lipid profiles in the
      short and medium term after metabolic surgery; however, the complications of
      metabolic surgery warrant further attention.

PMID- 29571635
TI  - Lack of correlation between gastroesophageal reflux disease symptoms and
      esophageal lesions after sleeve gastrectomy.
AB  - BACKGROUND: The postoperative development or worsening of gastroesophageal reflux
      disease (GERD) represents the major drawback of laparoscopic sleeve gastrectomy
      (SG). A GERD diagnosis is often based only on symptoms and proton pump inhibitors
      (PPI) intake, while objective tests like esophagogastroduodenoscopy and pH
      measurements are performed less frequently. OBJECTIVES: To evaluate the
      association between reflux symptoms and GERD-related esophageal lesions.
      SETTINGS: University hospital, Rome, Italy. METHODS: A comprehensive clinical
      control entailing GERD symptoms, PPI intake, and esophagogastroduodenoscopy was
      proposed to all patients who underwent SG between June 2007 and February 2011,
      irrespective of the presence of GERD symptoms. One hundred forty-four of 219
      patients agreed to take part in the study (follow-up rate: 65.8%). RESULTS: After
      a mean follow-up of 66 months, GERD symptoms and PPI intake were recorded in
      70.2% and 63.9% of patients, respectively. Mean visual analogue scale score was
      2.9 +/- 3.3. The overall frequency of erosive esophagitis was 59.8%, while
      nondysplastic Barrett's esophagus was detected in 13.1%. The frequency of
      esophageal biliary reflux was 68%. GERD symptoms and visual analogue scale score
      were not significantly associated with the development of erosive esophagitis and
      Barrett's esophagus and the severity of the esophageal lesions. Moreover, the
      frequency of erosive esophagitis and Barrett's esophagus in patients consuming
      PPI were similar to that of patients without PPI. CONCLUSION: Symptoms
      investigation alone is not a reliable tool to diagnose GERD after SG. The use of
      objective diagnostic tests, such as esophagogastroduodenoscopy, should be
      carefully considered in the postoperative follow-up schedule of SG patients.

PMID- 29571636
TI  - Comment on: is preoperative gastroscopy necessary prior to sleeve gastrectomy and
      Roux-en-Y gastric bypass?

PMID- 29571637
TI  - In response to: Comment on: laparoscopic sleeve gastrectomy combined with
      Rossetti fundoplication (R-sleeve) for treatment of morbid obesity and
      gastroesophageal reflux.

PMID- 29571638
TI  - Acute Onset of Severe Chest Pain Associated With Strenuous Sexual Activity.

PMID- 29571639
TI  - Lung Resection Surgery: Can We Prevent Unplanned Intubations?

PMID- 29571640
TI  - Comparison of Clinical Outcomes Between General Anesthesiologists and Cardiac
      Anesthesiologists in the Management of Left Ventricular Assist Device Patients in
      Noncardiac Surgeries and Procedures.
AB  - OBJECTIVE: To describe the authors' experience and comparative results after
      introducing noncardiac fellowship-trained anesthesiologists to a service
      previously managed by fellowship-trained cardiac anesthesiologists caring for
      left ventricular assist device (LVAD) patients undergoing low-risk noncardiac
      procedures with anesthesia. DESIGN: A retrospective chart review. SETTING: Single
      site academic medical center in the United States. INTERVENTIONS: Anesthesia and
      intraoperative therapy. MEASUREMENTS AND MAIN RESULTS: After initiating a brief
      training period for the noncardiac fellowship-trained anesthesiologists and
      blending the noncardiac anesthesiologists into the care of LVAD patients, the
      electronic medical records of 158 patients with an LVAD who underwent noncardiac
      procedures were reviewed. The cases were managed by either cardiac-trained
      anesthesiologists or noncardiac-trained anesthesiologists. Their performance was
      evaluated on the basis of technique and outcome. The parameters for technique
      were the use of intubation and mechanical ventilation, use of vasoactive
      medications, type of vasoactive medications administered, use of invasive
      monitoring, and type and amount of intravenous fluid administration. The outcomes
      examined included occurrence of intraoperative mean blood pressure <55 mmHg,
      intraoperative cardiac arrest, intraoperative device malfunction, thromboembolic
      complications, inability to complete procedure due to intraoperative nonsurgical
      complication, unplanned postoperative intensive care unit admission, unplanned
      hospital readmission within 30 days, and the 30-day postoperative mortality rate.
      This analysis demonstrated no statistically significant associations between the
      type of anesthesiologist and the use of fluid, amount of fluid given, use of
      vasopressors, or use of invasive monitoring devices. There were no significant
      differences in specific patient outcomes by anesthesia provider type.
      CONCLUSIONS: Patients with LVADs can be managed by either a noncardiac or a
      cardiac fellowship-trained anesthesiologist with similar technique and outcome
      during low-risk noncardiac procedures and surgeries.

PMID- 29571641
TI  - Clinical Study Designs and Sources of Error in Medical Research.

PMID- 29571642
TI  - One Lung Ventilation Using a Fastrach Endotracheal Tube in a Patient With
      Laryngectomy.

PMID- 29571643
TI  - Acute Kidney Injury After Total Arch Replacement Combined With Frozen Elephant
      Trunk Implantation: Incidence, Risk Factors, and Outcome.
AB  - OBJECTIVES: Acute kidney injury (AKI) is common after thoracic aortic surgery and
      is a significant predictor of morbidity and mortality. Total arch replacement
      (TAR) combined with frozen elephant trunk (FET) implantation has been reported to
      produce satisfactory clinical outcomes, whereas several features of the surgical
      procedure may induce postoperative AKI. The authors aimed to clarify the
      incidence of and risk factors for postoperative AKI and the association of AKI
      with short-term outcomes. DESIGN: This study was a retrospective analysis of a
      prospectively collected cohort. A multivariate logistic regression model was used
      to identify predictors of postoperative AKI. SETTING: Single center.
      PARTICIPANTS: Clinical data were analyzed for 553 consecutive patients who
      underwent TAR combined with FET implantation between 2013 and 2016.
      INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Postoperative AKI was defined
      using the Kidney Disease Improving Global Outcomes criteria. Postoperative AKI
      occurred in 77.6% of the whole cohort. Patients in stage 3 AKI were associated
      with a higher incidence of major adverse events and in-hospital and 90-day
      mortality (p < 0.001, p < 0.05, p < 0.01, respectively). In the multivariate
      analysis, male sex (odds ratio [OR] 1.94; 95% confidence interval [95% CI] 1.22
      3.18; p = 0.005); older age (per 10 years) (OR 1.37; 95% CI 1.14-1.67; p =
      0.001); elevated body mass index (per 5 kg/m2) (OR 1.41; 95% CI 1.08-1.87; p =
      0.01); and prolonged cardiopulmonary bypass duration (per 30 minutes) (OR 1.17;
      95% CI 1.01-1.37; p = 0.03) were identified as independent predictors of
      postoperative AKI. CONCLUSION: TAR combined with FET implantation carries a high
      risk for postoperative AKI compared with other types of thoracic aortic
      surgeries. Cardiopulmonary bypass duration was identified as the only modifiable
      predictor of AKI, and patients may benefit from moderate hypothermic circulatory
      arrest instead of deep hypothermic circulatory arrest.

PMID- 29571644
TI  - Large-Scale Implementation of Structured Reporting of Adnexal Masses on
      Ultrasound.
AB  - PURPOSE: The aim of this article is to describe the development and
      implementation of structured reporting of adnexal mass findings on pelvic
      ultrasound in a large integrated health care delivery system. METHODS: A
      structured reporting system that includes standardized terminology for describing
      adnexal masses on ultrasound was developed by a multidisciplinary team of
      radiologists, gynecologists, and gynecologic oncologists on the basis of
      literature review and internal data. The system uses a reporting template that
      requires radiologists to assign abnormal adnexal masses to one of five possible
      categories on the basis of standardized criteria: category 0, 1, 2, or 3 for
      masses <10 cm, to reflect increasing concern for malignancy, and category X for
      masses >10 cm. Unique predefined hashtags were linked to each category to enable
      electronic data extraction, and a hard stop feature was installed that prevents
      reports from being finalized without a category designation. In 2014, after a 3
      month pilot study, large-scale implementation was supported by an educational
      campaign consisting of web-based conferences, e-mail announcements, and local
      presentations. Clinical management recommendations on the basis of category and
      other clinical factors were provided in a separate practice resource for
      clinicians. RESULTS: Analysis of adherence revealed that 93% of the approximately
      12,000 reports describing abnormal adnexal masses in 2016 included category
      designations. Feedback from referring providers via an anonymous survey indicated
      high levels of satisfaction with reports. CONCLUSIONS: Multidisciplinary
      collaboration and leveraging of technology enabled large-scale implementation of
      structured reporting with high levels of adherence among radiologists and
      improved satisfaction among referring providers.

PMID- 29571645
TI  - Musculoskeletal Injuries Affecting Radiologists According to the 2017 ACR Human
      Resources Commission Workforce Survey.
AB  - Practice leaders surveyed in the 2017 ACR Human Resources Commission workforce
      survey reported that 25% of the radiologists or radiation oncologists they
      supervised had neck pain, 32% had low back pain, and 16% were dealing with a
      repetitive stress injury. The prevalence rates of these musculoskeletal ailments
      among radiologists and radiation oncologists were consistent with those reported
      in the literature in other populations. However, these prevalence rates may be
      underestimated because practice leaders, not the radiologists themselves, were
      surveyed, and the leaders may not be aware of all injuries.

PMID- 29571646
TI  - Ultrasound and Dual-Energy X-Ray Absorptiometry Report Transcription Error Rates
      and Strategies for Reduction.
AB  - PURPOSE: Radiologists play an essential role in patient care by providing
      accurate and timely results. An error-free radiology report is an expectation of
      both patients and referring physicians. Software is currently available that can
      eliminate measurement and side types of errors while saving radiologists and
      sonographers time. The objectives of this study were to evaluate the potential
      reduction in report errors, estimate the potential time savings associated with
      implementation, and conduct a cost-benefit analysis of implementing two software
      programs. METHODS: Data on the number of measurement errors and side errors in
      ultrasound and dual-energy x-ray absorptiometry reports were collected, and the
      time required for data entry that the software would reduce was measured by
      report type. Generalized estimating equations regression was used to estimate
      error rates and data entry times and corresponding 95% confidence intervals by
      report type for radiologists and sonographers. Current wages and report volumes
      were then applied to the time savings to estimate the annual wage savings.
      Projected volume increases were applied to the annual estimates to generate a 5
      year savings estimate. RESULTS: Overall, measurement errors occurred in 6% to 28%
      of ultrasound reports, depending on the report type. Side errors were rare. It
      was estimated that over 5 years, the software could save $693,777 in radiologist
      wages and $130,771 in sonographer wages, a total of $824,548 (range, $621,866
      $1,039,714). CONCLUSIONS: The use of data integration software would both
      significantly reduce errors in ultrasound and dual-energy x-ray absorptiometry
      reports and save a considerable amount of time and money.

PMID- 29571647
TI  - [LEOPARD syndrome: A variant of Noonan syndrome with lentigines].

PMID- 29571648
TI  - [Seizing opportunities and breaking barriers to ensure the transfer of knowledge
      based on better clinical evidence].

PMID- 29571650
TI  - Early assessment of response to chemotherapy in lung cancer using dynamic
      contrast-enhanced MRI: a proof-of-concept study.
AB  - AIM: To evaluate the early treatment response to chemotherapy in patients with
      lung cancer using dynamic contrast-enhanced (DCE) magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: Twenty-two patients with lung cancer underwent DCE
      MRI before chemotherapy and 1 week after the start of the first course of
      chemotherapy. Pharmacokinetic parameters (Ktrans, Kep, and Ve) derived from DCE
      MRI were generated using the post-processing platform. These parameters and
      corresponding changes were compared between responders and non-responders after
      treatment using Student's t or Mann-Whitney U-tests. Diagnostic efficiency of
      kinetic parameters in differentiating responders from non-responders after 1 week
      of chemotherapy was also investigated. RESULTS: Thirteen responders after 1 week
      of chemotherapy had a significant decrease in Ktrans and Ve compared with the
      pretreatment value (p<0.05), and had no significant changes in Kep (p>0.05). Nine
      non-responders had no significant changes in Ktrans, Kep, and Ve compared with
      the pretreatment value (p>0.05). Changes in Ktrans (DeltaKtrans) were
      significantly larger in responders than that in non-responders (p<0.05). Changes
      in Ve and Kep (DeltaVe andDeltaKep) were without statistical significance after
      treatment between responders and non-responders (p>0.05). The cut-off value of
      DeltaKtrans in best predicting tumour's chemotherapeutic response was 0.032/min
      and the corresponding AUC (area under the curve), sensitivity, specificity, and
      accuracy were 0.821, 84.62%, 77.78%, and 81.82%, respectively. CONCLUSION: DCE
      MRI may be useful for evaluating the early response to chemotherapy in patients
      with lung cancer, but larger, more definitive studies are needed.

PMID- 29571649
TI  - Prediction of tumor biological characteristics in different colorectal cancer
      liver metastasis animal models using 18F-FDG and 18F-FLT.
AB  - BACKGROUND: Positron emission tomography (PET) is a noninvasive method to
      characterize different metabolic activities of tumors, providing information for
      staging, prognosis, and therapeutic response of patients with cancer. The aim of
      this study was to evaluate the feasibility of 18F-fludeoxyglucose (18F-FDG) and
      3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET in predicting tumor biological
      characteristics of colorectal cancer liver metastasis. METHODS: The uptake rate
      of 18F-FDG and 18F-FLT in SW480 and SW620 cells was measured via an in vitro cell
      uptake assay. The region of interest was drawn over the tumor and liver to
      calculate the maximum standardized uptake value ratio (tumor/liver) from PET
      images in liver metastasis model. The correlation between tracer uptake in liver
      metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.
      RESULTS: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented
      a higher rate of liver metastases. The uptake rate of 18F-FDG in SW480 and SW620
      cells was 6.07% +/- 1.19% and 2.82% +/- 0.15%, respectively (t = 4.69, P = 0.04);
      that of 18F-FLT was 24.81% +/- 0.45% and 15.57% +/- 0.66%, respectively (t =
      19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were
      significantly higher in SW480 tumors than those in SW620 tumors. A moderate
      relationship was detected between metastases in the liver and 18F-FLT uptake in
      primary tumors (r = 0.73, P = 0.0019). 18F-FLT uptake was also positively
      correlated with the expression of CD44 in liver metastases (r = 0.81, P =
      0.0049). CONCLUSIONS: The uptake of 18F-FLT in metastatic tumor reflects
      different biological behaviors of colon cancer cells. 18F-FLT can be used to
      evaluate the metastatic potential of colorectal cancer in nude mice.

PMID- 29571651
TI  - Complete genome sequence of Bifidobacterium choerinum FMB-1, a resistant starch
      degrading bacterium.
AB  - The strain Bifidobacterium choerinum FMB-1, a bacterium with a strong ability to
      degrade resistant starch (RS), was isolated from rumen fluids of Korean native
      cattle (Bos taurus coreanae). Degradation experiments revealed that it could
      degrade approximately 80% of native granular starches within 8 h. Although B.
      choerinum has strong RS degradation abilities, a completed genomic resource has
      not yet been proposed. Here we present the complete whole genome data of B.
      choerinum FMB-1. It consists of a circular chromosome (2,257,294 bp) and one
      plasmid (11,012 bp). Genome analysis revealed that at least 11 protein-coding
      genes were related to alpha-glucan degradation. The abundance of these genes may
      affect the efficacy of granular starch degradation. We also found the existence
      of antimicrobial resistance genes in the genome, which were not reported in other
      B. choerinum genomes. The whole genome information of B. choerinum FMB-1 could
      improve the understanding of the RS degradation mechanism of bovine gut
      microorganisms.

PMID- 29571652
TI  - The complete genome sequence of the first hesperiid-infecting alphabaculovirus
      isolated from the leguminous pest Urbanus proteus (Lepidoptera: Hesperiidae).
AB  - Baculoviruses are insect viruses largely used as expression vectors and
      biopesticides. These viruses can efficiently infect the larval stage of several
      agricultural pests worldwide causing a lethal disease. In this work, we found a
      novel baculovirus isolated from the larval stage of Urbanus proteus (L.), the
      bean leafroller and characterized its complete genome. This is an important pest
      of several leguminous plants in Brazil and belongs to the butterfly family
      Hesperiidae, from where no baculovirus genome sequence has been described. This
      new virus was shown to have the smallest genome among all alphabaculoviruses
      sequenced to date, with 105,555 bp and 119 putative ORFs. We found ten unique
      genes, seven bro, and the 38 baculovirus core genes. UrprNPV was found to be
      related to the Adoxophyes-infecting baculoviruses AdorNPV and AdhoNPV with high
      genetic distance and a long branch length. Interestingly, few individual core
      gene-based phylogenies were found to support the relationship of UrprNPV to both
      AdorNPV and AdhoNPV. Importantly, the increase in number of completely sequenced
      baculovirus points to a very exciting way to understand baculovirus and its
      evolution and could potentially help the use of baculovirus as both biopesticides
      and expression vectors.

PMID- 29571653
TI  - Design, synthesis and biological evaluation of anti-pancreatic cancer activity of
      plinabulin derivatives based on the co-crystal structure.
AB  - Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a
      derivative of plinabulin), a total of 18 novel plinabulin derivatives were
      designed and synthesized. Their biological activities were evaluated against
      human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e
      exhibited potent activities with IC50 at 1.56 and 1.72 nM, respectively. The
      tubulin polymerization assay indicated that these derivatives could inhibit
      microtubule polymerization. Furthermore, the interaction between tubulin and
      these compounds were elucidated by molecular docking. The binding modes of
      Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H
      pi interaction was observed between the aromatic hydrogen of thiophene moiety
      with Phe20, which could enhance their binding affinities.

PMID- 29571655
TI  - Rapidly expanding mixed lesion of the maxilla in a 17-month-old boy.

PMID- 29571654
TI  - The anuran skin peptide bradykinin mediates its own absorption across epithelial
      barriers of the digestive tract.
AB  - When faced with a potential predator, a wide range of frog species secrete a
      mixture of peptide toxins from their skin to defend themselves. We have recently
      shown that antimicrobial peptides (AMPs) in a frog's defensive poison enhance the
      uptake of these peptides across epithelia, thereby speeding up the process of
      predator intoxication. This study provides evidence that bradykinin, a widespread
      peptide toxin in anurans (frogs), is capable to pass through epithelial barriers
      independent of this delivery system. We quantified bradykinin peptides secreted
      by Bombina orientalis during acute stress, and found that at biologically
      relevant concentrations, bradykinin passage across model epithelia occurs even in
      the absence of AMPs. Monitoring of transepithelial electric resistance showed
      that bradykinin treatment caused a subtle yet prolonged reduction in barrier
      function, indicating that the peptide itself is capable to increase the
      permeability of epithelia. Yet, bradykinin does not cause cells to leak lactate
      dehydrogenase, suggesting that it does not damage cell membranes. Moreover,
      imaging of bradykinin-treated monolayers shows no endocytosis of fluorescent
      propidium iodide, indicating that the peptide does not perforate cell membranes
      at smaller scale and therefore is unlikely to cross epithelia via a transcellular
      passage. Together, these observations suggest that bradykinin, unlike other
      amphibian neuropeptide toxins, mediates its own passage across mucosal barriers,
      possibly through a paracellular route. This "self-administering" property,
      combined with the fact that bradykinins can potently disturb multiple
      physiological processes, could explain why these peptides are one of the most
      widespread antipredator peptides in the defensive secretions of frogs.

PMID- 29571656
TI  - Detection of major histocompatibility complex molecules in processed allogeneic
      bone blocks for use in alveolar ridge reconstruction.
AB  - OBJECTIVES: Because processed allogenic bone blocks contain remnants of cells and
      other organic material, the present study examined the putative presence of major
      histocompatibility complex (MHC) molecules in protein extracts derived from
      processed allogeneic bone blocks. STUDY DESIGN: Protein content and the
      immunogenic potential of 3 different processed allografts (Osteograft, DIZG,
      Berlin, Germany; Caput femoris, DIZG, Berlin, Germany; Human Spongiosa, Charite
      Tissue Bank, Berlin, Germany) were assessed by protein extraction and analysis of
      the presence of MHC class 1 and 2 molecules prior to grafting. MHC concentration
      was measured by using enzyme-linked immunosorbent assay. RESULTS: Protein content
      in the allograft materials varied between 0.87 and 1.61 ug protein/mg. In the
      allograft Human Spongiosa, no MHC was detected, whereas in the allogeneic bone
      blocks Osteograft and Caput femoris MHC 1 (0.04-0.037 ng/mg graft material) and
      in Osteograft MHC class 2 molecules were detectable. CONCLUSIONS: The results of
      the present study suggest that despite thorough processing, a potential
      antigenicity of allografts is not eliminated. MHC molecules in allografts may
      sensitize the immune system.

PMID- 29571657
TI  - Response to Letter to the Editor re 'Urinary tract infection in children:
      Diagnosis, treatment, imaging - Comparison of current guidelines'.

PMID- 29571658
TI  - Cryopreservation of testicular tissue in pre-pubertal and adolescent boys at risk
      for infertility: A low risk procedure.
AB  - INTRODUCTION: Cryopreservation of testicular tissue (TT) has become an
      increasingly attractive option for fertility preservation (FP), particularly for
      pre-pubertal boys at risk for gonadotoxicity from cancer therapy. At our
      institution, all at-risk families undergo counseling regarding infertility risk
      and available FP strategies, including this vulnerable patient population. As the
      technology required to use the acquired tissue is, as yet, unproven, it is
      paramount to document minimal morbidity and complications from this procedure.
      Herein, we report these outcomes for all pre-pubertal patients who have undergone
      TT biopsies for FP. METHODS: We retrospectively reviewed consecutive patients who
      underwent unilateral open TT biopsies between January 2014 and December 2016.
      Patient diagnosis, age, concomitant procedures, anesthetic type, complications,
      procedure times, planned therapy, and bleeding were evaluated. RESULTS: Of a
      total of 34 patients, mean age at biopsy was 6.9 +/- 4.4years. Diagnoses
      included: leukemia/lymphoma (n = 12), solid tumors (n = 15) and non-neoplastic
      disorders (hemophagocytic lymphohistiocytosis, aplastic anemia; n = 7). Twenty
      two patients (64.7%) were scheduled for stem cell transplantation. Eleven (32.4%)
      patients had not received any chemotherapy prior to TT biopsy, while all others
      had exposure preceding the biopsy. Biopsies were performed in conjunction with
      other procedures (central line placement, bone marrow biopsy, lumbar puncture,
      lymph node biopsy) in 29 cases (85.3%), with stand-alone procedures performed in
      the remainder (n = 5). In stand-alone cases, mean anesthetic time was 22 +/- 8.7
      min. Overall, two (5.9%) patients had complications after biopsy: 1) ipsilateral
      epididymo-orchitis (resolved with antibiotics) and 2) ipsilateral torsed appendix
      testis (managed conservatively) (Table). CONCLUSION: In this series, pre-pubertal
      TT biopsy for cryopreservation was safely performed, and was most often
      coordinated concomitantly with other medically necessary procedures. The safety
      profile reported herein supports performing this procedure while technological
      advances fulfill the requirements to make it a viable option for future
      fertility.

PMID- 29571659
TI  - Urology mythbusters: Radiation and radiophobia.
AB  - In this episode of Mythbusters we critically examine the premise that there is
      strong biological and epidemiologic evidence that radiation exposure at levels
      associated with modern genitourinary diagnostic imaging increases the risk of
      subsequent malignancy, especially in children.

PMID- 29571660
TI  - Bioactive dental materials-Do they exist and what does bioactivity mean?

PMID- 29571661
TI  - Whole-Exome Sequencing Identifies Two Discrete Druggable Signaling Pathways in
      Follicular Thyroid Cancer.
AB  - BACKGROUND: Thyroid cancer is the most common endocrine malignancy, with
      continuously increasing incidence. Follicular thyroid cancer (FTC) accounts for
      approximately 10% to 15% of these cases and is known to be associated with
      several gene mutations. The purpose of this study was to identify novel
      therapeutic targets in FTC using whole-exome sequencing (WES) and bioinformatics
      analysis. STUDY DESIGN: Whole-exome sequencing was performed on 6 established FTC
      cell lines. Stringent false-proof filtering and exclusion of synonymous and known
      polymorphisms yielded novel missense, nonsense, and splice-site single nucleotide
      variants (SNV). Gene variants were analyzed for structural, functional, and
      evolutionary properties using GO (Gene Ontology), Pfam (Protein Families), and
      KEGG (Kyoto Encyclopedia of Genes and Genomes) searches by STRING (Search Tool
      for the Retrieval of Interacting Genes/Proteins) and GORILLA (Gene Ontology
      enRIchment anaLysis and visuaLizAtion tool) analyses. A false discovery rate of
      <0.5 was used to denote significantly enriched signaling pathways. RESULTS: An
      average of 657 (range 366 to 1,158) SNVs including 31 (range 12 to 53) known
      cancer driver genes were identified in FTC cell line exomes. The SNV burden,
      distribution, frequency, and signature followed the known thyroid mutation
      profiles, without chromosomal bias. Recurrently mutated cancer driver genes
      included FRG1 (6/6), CDC27, NCOR1, PRSS1 (5/6), AHCTF1, MUC20, PABPC1, and PABPC3
      (4/6). Pathway analysis using bioinformatics tools STRING and GORILLA segregated
      FTC cell lines into 2 druggable signaling groups showing dominant RAS/ERK1-2/AKT
      and CDK1/CyclinB signaling pathway targets. CONCLUSIONS: Next-generation
      sequencing tools can be used to identify druggable signaling targets for
      precision treatment of FTCs.

PMID- 29571662
TI  - Persistent Maladies: The Case of Two-Mind Syndrome.

PMID- 29571663
TI  - Pint-Sized Public Relations: The Development of Reputation Management.
AB  - Until recently, many psychologists were skeptical that young children cared about
      reputation. New evidence suggests that by age five, children begin to understand
      the broad importance of reputation and to engage in surprisingly sophisticated
      impression management. These findings prompt exciting new questions about the
      development of a fundamental social competency.

PMID- 29571664
TI  - The Mythical Number Two.
AB  - It is often said that there are two types of psychological processes: one that is
      intentional, controllable, conscious, and inefficient, and another that is
      unintentional, uncontrollable, unconscious, and efficient. Yet, there have been
      persistent and increasing objections to this widely influential dual-process
      typology. Critics point out that the 'two types' framework lacks empirical
      support, contradicts well-established findings, and is internally incoherent.
      Moreover, the untested and untenable assumption that psychological phenomena can
      be partitioned into two types, we argue, has the consequence of systematically
      thwarting scientific progress. It is time that we as a field come to terms with
      these issues. In short, the dual-process typology is a convenient and seductive
      myth, and we think cognitive science can do better.

PMID- 29571665
TI  - Is the Type 1/Type 2 Distinction Important for Behavioral Policy?
AB  - Melnikoff and Bargh provide a powerful critique of the Type 1/Type 2 distinction
      as a typology of cognitive processes. But such a distinction may, nonetheless, be
      useful in highlighting the need for behaviorally inspired public policy.

PMID- 29571666
TI  - Presence of Clostridium difficile in poultry and poultry meat in Egypt.
AB  - C. difficile has been recognized as a potential zoonotic agent encouraging
      investigations of C. difficile prevalence and ribotypes in animals. Here we
      report the prevalence and diversity of Egyptian C. difficile in I) samples from
      healthy poultry (n = 50), II) samples from diseased poultry (n = 54), and III)
      poultry meat (n = 150). Thirteen isolates were obtained from seven healthy and
      five diseased animals, but no C. difficile was cultured from poultry meat. The
      isolated C. difficile strains belonged to 3 different PCR-ribotypes (039/2, 205
      and 001/FLI01). The detection of strains related to RT 001 known for its ability
      to cause disease in humans makes poultry a potential reservoir for pathogenic C.
      difficile.

PMID- 29571667
TI  - Impella support following emergency percutaneous balloon aortic valvuloplasty in
      patients with severe aortic valve stenosis and cardiogenic shock.
AB  - BACKGROUND: To investigate the feasibility and outcomes of Impella 2.5 support in
      patients with severe aortic valve stenosis (AS) and cardiogenic shock (CS), who
      underwent emergency percutaneous balloon aortic valvuloplasty (BAV) with or
      without percutaneous coronary intervention (PCI). METHODS AND RESULTS: We
      retrospectively analyzed a consecutive series of patients with severe AS and CS
      who underwent Impella 2.5 support following emergency BAV with or without
      subsequent PCI. Outcome data included 30-day outcomes, periprocedural as well as
      throughout the circulatory support period complications. Eight patients with
      severe AS and CS were identified. Impella 2.5 implantation was successful
      following emergency BAV in all patients attempted. Additional PCI was performed
      in four patients. No periprocedural deaths or periprocedural neurologic events
      occurred. Mean procedure time was 125.9 min (range 64-210 min). Mortality at 30
      days was 50%. CONCLUSIONS: Impella 2.5 can be used as hemodynamic support in
      patients with severe AS and CS following emergency percutaneous BAV and may help
      to improve tolerability of PCI in these high-risk patients.

PMID- 29571668
TI  - Odor preference and olfactory memory are impaired in Olfaxin-deficient mice.
AB  - Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein,
      is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb
      (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in
      their glutamatergic terminal localization, kidney-type glutaminase (KGA)
      interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein
      causes human Cayman ataxia and ataxia in the mutant mouse, the function of
      Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice
      (Prune2Ex16-/-; knock out [KO] mice) using the CRISPR/Cas9 system, during which
      the exon 16 containing start codon of Olfaxin mRNA was deleted. Exon 16 has 80
      nucleotides and is contained in four of five Prune2 isoforms, including PRUNE2,
      BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels of Olfaxin mRNA and Olfaxin protein
      in the OB and piriform cortex of KO mice significantly decreased. Although Prune2
      mRNA also significantly decreased in the spinal cord, the gross anatomy of the
      spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of
      the sensory and motor system was not observed in KO mice. Therefore, in the
      current study, we examined the role of Olfaxin in the olfactory system where
      PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in
      KO mice using opposite-sex urinary scents as well as a non-social odor stimulus
      (almond). Results of the odor-aversion test demonstrated that odor-associative
      learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch
      in the piriform cortex was not observed in KO mice. These results indicated that
      Olfaxin may play a critical role in odor preference and olfactory memory.

PMID- 29571669
TI  - Chronic lymphocytic leukemia and infection risk in the era of targeted therapies:
      Linking mechanisms with infections.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the
      world. Patient with CLL are at particular risk for infections due to inherent
      disease-related immune dysfunction in addition to the effect of certain systemic
      therapies on the immune system. The advent of B-cell receptor (BCR) inhibitors
      such as ibrutinib and idelalisib has led to a practice change that utilizes these
      targeted agents in the treatment of CLL, either in place of chemoimmunotherapy
      (CIT) or in later line settings. In this paper, we review the pathophysiology of
      immune dysfunction in CLL, the spectrum of immunodeficiency with the various
      therapeutic agents along with prevention strategies with a focus on targeted
      therapies.

PMID- 29571670
TI  - Maxillary tumour-induced osteomalacia.
AB  - Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal
      phosphate wasting that results in severe hypophosphatemia, defective vitamin D
      metabolism, and osteomalacia. In the case reported here, maxillary TIO was not
      diagnosed for 6years, although initial complaints were reported when the patient
      was 12years old. Meanwhile she suffered from profound growth limitation, pain,
      weakness, and spontaneous multiple bone fractures, culminating in complete loss
      of ambulatory ability and severe limitation in daily activities. At age 18years,
      she finally received an accurate diagnosis and definitive treatment was
      administered. She underwent a partial maxillectomy with complete removal of the
      tumour, resulting in a full cure. Shortly afterwards the patient regained the
      ability to walk, no longer needing the wheelchair to which she had been confined.
      This definitive diagnosis was based on three modalities: (1) fibroblast growth
      factor 23 analysis (high levels of the secreted hormone were found on the left
      side of the maxilla in the facial vein and pterygoid plexus, pinpointing the
      tumour location), (2) octreotide scan, and (3) 68Ga-DOTA-NOC-PET/CT. TIO removal
      via partial maxillectomy led to a complete reversal of this patient's health
      condition, restoring her ability to walk and function. The importance of prompt
      employment of these diagnostic modalities and the high level of clinical
      suspicion required in such cases are clear.

PMID- 29571671
TI  - Impact of particulate deproteinized bovine bone mineral and porous titanium
      granules on early stability and osseointegration of dental implants in narrow
      marginal circumferential bone defects.
AB  - The use of two particulate bone graft substitute materials in experimental narrow
      marginal peri-implant bone defects was investigated with respect to early bone
      healing and implant stability. Porous titanium granules, oxidized white porous
      titanium granules (WPTG), and demineralized bovine bone mineral (DBBM) were
      characterized in vitro, after which the two latter materials were tested in
      experimental peri-implant bone defects in six minipigs, with empty defects as
      control. After mandibular premolar extraction, the top 5mm of the alveoli were
      widened to 6mm in diameter, followed by the placement of six implants, three on
      each side, in each pig. Six weeks of healing was allowed. The WPTG showed better
      mechanical properties. No significant differences in resonance frequency analysis
      were found directly after compacting or healing, and similar quantities of defect
      bone formation were observed on micro-computed tomography for all groups.
      Histomorphometric analysis demonstrated a more coronal bone-to-implant contact in
      the DBBM group, which also displayed more defect bone fill as compared to the
      WPTG group. The better mechanical properties observed for WPTG appear of
      negligible relevance for the early stability and osseointegration of implants.

PMID- 29571672
TI  - CDK5-mediated phosphorylation of CP190 may regulate locomotor activity in adult
      female Drosophila.

PMID- 29571673
TI  - Small peptides, big roles - RALFs regulate pollen tube growth and burst in plant
      reproduction.

PMID- 29571674
TI  - Ampullary Dieulafoy: An Unusual Cause of Obscure Gastrointestinal Bleeding.

PMID- 29571675
TI  - An Infected Aortic Aneurysm After Successful Treatment of Nontyphoidal Salmonella
      Gastroenteritis.

PMID- 29571676
TI  - Hepatitis C Virus-Related Cryoglobulinemic Vasculitis.

PMID- 29571677
TI  - Abdominal Pain Caused by a Second Gall Bladder and Separate Cystic Duct.

PMID- 29571678
TI  - Transvaginal sonographic assessment of bladder wall thickness; methodology and
      statistical issues on reproducibility and accuracy.

PMID- 29571679
TI  - Comparison of microscopic and molecular enumeration methods for insect viruses:
      Cryptophlebia leucotreta granulovirus as a case study.
AB  - Enumeration techniques were compared for quantification of the South African
      isolate of Cryptophlebia leucotreta granulovirus (CrleGV-SA), used as a
      biopesticide to control false codling moth (Thaumatotibia leucotreta), an insect
      pest of various fruits and nuts, including citrus. The routine enumeration method
      for CrleGV-SA virus particles in experimentation and production of CrleGV-SA
      biopesticides is dark field microscopy. This method was compared with
      spectrophotometry, scanning electron microscopy (SEM) and real time quantitative
      polymerase chain reaction (qPCR). The purpose was to develop an accurate and
      reliable routine enumeration method for CrleGV-SA occlusion bodies (OBs) and to
      validate the use of dark field microscopy. Purified and semi-purified CrleGV-SA
      viral stocks were used. Spectrophotometry was not a suitable or accurate
      enumeration method. Dark field microscopy and SEM were accurate and statistically
      comparable (p = 0.064), validating the use of dark field microscopy as an
      enumeration method for granulovirus (GV). However, SEM has superior resolution
      and the advantage of easily distinguishing virus particles from debris in semi
      purified viral stock preparations. A quantitative PCR technique has been
      developed based on use of specific oligonucleotide primers for the granulin gene.
      This has the advantage of not being affected by contamination with non-biological
      debris or biological material, which impact on the other methods.

PMID- 29571680
TI  - Intimate partner violence during pregnancy and behavioral problems in children
      and adolescents: a meta-analysis.
AB  - OBJECTIVE: To evaluate the association of intimate partner violence during the
      gestational period and the development of externalizing and internalizing
      behavioral problems in children and adolescents. SOURCE OF DATA: A meta-analysis
      of cohort and case-control studies was performed, using studies selected from
      electronic databases. Eligible studies included women who experienced intimate
      partner violence during pregnancy and their children's behavioral problems. These
      problems encompass two groups: externalizing problems (expressed by
      hyperactivity, aggressive and challenging behavior, and delinquency) and
      internalizing problems (represented by depressive moods, anxiety, and somatic
      symptoms). The risk of bias was assessed by the Newcastle-Ottawa Quality
      Assessment Scale (NOS) and the quality of evidence by the Grading of
      Recommendations, Assessment, Development and Evaluation (GRADE). RevMan 5.3
      software was used for the meta-analysis. DATA SYNTHESIS: Of the 687 eligible
      articles, only seven met all inclusion criteria and consisted of 12,250
      mother/child pairs. The age range of the assessed children varied from 10 months
      to 16 years. The odds of internalizing problems in children exposed to prenatal
      violence were two-fold higher (OR=2.10, 95% CI: 1.17-3.76) and that of
      externalizing problems were 1.9-fold higher (95% CI: 1.28-2.83), when compared to
      children of unexposed mothers. CONCLUSION: The results of this study are
      consistent with the hypothesis that women's exposure to intimate partner violence
      during pregnancy may be associated with behavioral problems of their children,
      emphasizing the need for greater understanding about the vulnerability of
      children to adversity in early ages.

PMID- 29571681
TI  - Randomized clinical trial to change parental practices for drug use in a
      telehealth prevention program: a pilot study.
AB  - OBJECTIVES: Programs for parents have been found to have a direct positive impact
      on reducing the consumption of psychoactive substances by adolescents, as well as
      having an indirect impact on reducing risk factors and increasing protective
      factors. The present study aimed to verify if a telehealth prevention program
      based on a brief motivational intervention helps to reduce parental risk
      practices and increase parental protective practices for drug use in comparison
      with psychoeducation. METHODS: A pilot randomized controlled trial was performed
      at the National Service of Guidance and Information on Drug Use (Ligue 132), from
      September 2014 to December 2015, with the parents of adolescents (n=26). The
      outcome measures were parental style, risk, and protective parental practices.
      RESULTS: The brief motivational intervention was found to be more effective than
      psychoeducation in reducing the negligent behavior of parents. Furthermore, when
      comparing pre- and post-intervention data, the brief motivational intervention
      helped to change parental style and the large majority of parental practices:
      increasing positive monitoring, as well as decreasing physical abuse, relaxed
      discipline, inconsistent punishment, and negative monitoring. CONCLUSIONS: These
      results demonstrate that the telehealth intervention is effective in modifying
      the parental practices known to help in preventing drug use. Studies with more
      number of subjects are required so that the results can be substantiated and
      generalized.

PMID- 29571682
TI  - Protocol to obtain targeted transcript sequence data from snake venom samples
      collected in the Colombian field.
AB  - Snake venoms are a mixture of different molecules that can be used in the design
      of drugs for various diseases. The study of these venoms has relied on strategies
      that use complete venom extracted from animals in captivity or from venom glands
      that require the sacrifice of the animals. Colombia, a country with political and
      geographical conflicts has difficult access to certain regions. A strategy that
      can prevent the sacrifice of animals and could allow the study of samples
      collected in the field is necessary. We report the use of lyophilized venom from
      Crotalus durissus cumanensis as a model to test, for the first time, a protocol
      for the amplification of complete toxins from Colombian venom samples collected
      in the field. In this protocol, primers were designed from conserved region from
      Crotalus sp. mRNA and EST regions to maximize the likelihood of coding sequence
      amplification. We obtained the sequences of Metalloproteinases II, Disintegrins,
      Disintegrin-Like, Phospholipases A2, C-type Lectins and Serine proteinases from
      Crotalus durissus cumanensis and compared them to different Crotalus sp sequences
      available on databases obtaining concordance between the toxins amplified and
      those reported. Our strategy allows the use of lyophilized venom to obtain
      complete toxin sequences from samples collected in the field and the study of
      poorly characterized venoms in challenging environments.

PMID- 29571684
TI  - Authors' Response to Letter to the Editor: Adherence in ART: A Comment on Pina et
      al. (2017).

PMID- 29571685
TI  - Emotional Support, Active Coping, and ART Adherence in Young African American Men
      who have Sex With Men: A Pilot Mediation Model.

PMID- 29571686
TI  - "I like talking to people on the computer": Outcomes of a home-based intervention
      to develop social media skills in youth with disabilities living in rural
      communities.
AB  - PURPOSE: To investigate the effectiveness of a home-based social media use
      intervention to enhance the social networks of rural youth with disabilities.
      METHOD: Participants were nine youth (mean age = 17.0 years) with disabilities
      from two rural Australian communities. The intervention consisted of providing
      appropriate assistive technology and social media training on individualised
      goals. Using mixed methods, quantitative (a single group pre-post) and
      qualitative (interviews with participants and their carers) measures were used to
      examine outcomes of training, individual experiences of the intervention, and
      changes to online social networks. RESULTS: Participants increased their
      performance and satisfaction with performance on social media problem areas post
      intervention; paired t-tests showed statistical significance at p < .001. There
      was also a significant increase in the number of online communication partners;
      Wilcoxon Signed Ranks showed statistical significance at p < .05. The interviews
      highlighted increased social participation, independence and improvements to
      literacy. Ongoing parental concerns regarding cyber safety and inappropriate
      online content were noted. CONCLUSIONS: The findings suggest that social media
      training is a feasible method for increasing social networks among rural-based
      youth with disabilities. To sustain ongoing benefits, parents need knowledge and
      training in integrating assistive technology and social media.

PMID- 29571688
TI  - Validity and Reliability of the Healthy Families Survey: A Key Component of the
      Maryland Supplemental Nutrition Assistance Program-Education (SNAP-Ed)
      Evaluation.
AB  - OBJECTIVE: This study established the validity and reliability of the Healthy
      Families Survey, a 45-item survey measuring nutrition and physical activity
      behaviors among children and parents enrolled in the Maryland Supplemental
      Nutrition Assistance Program-Education. METHODS: Analysis included 1,376 pretest
      surveys. A factor analysis was conducted to establish construct validity, item
      analyses were conducted to determine item relevance for the target population,
      and Cronbach alpha was established to assess internal reliability. RESULTS: The
      factor analysis extracted 9 factors, with 91% of variables loading appropriately
      (>+0.30 loading) onto factors. Item analyses identified 6 variables with low
      (<0.20) or high (>0.80) mean values at baseline. Seven of the 9 subscales had
      Cronbach alpha >= .60. CONCLUSIONS AND IMPLICATIONS: The Healthy Families Survey
      demonstrated both strong construct validity and internal reliability and can be
      used by Supplemental Nutrition Assistance Program-Education agencies to assess
      child and parent nutrition and physical activity behaviors.

PMID- 29571689
TI  - Reply by Authors.

PMID- 29571687
TI  - An Extended Guinier Analysis for Intrinsically Disordered Proteins.
AB  - Guinier analysis allows model-free determination of the radius of gyration (Rg)
      of a biomolecule from X-ray or neutron scattering data, in the limit of very
      small scattering angles. Its range of validity is well understood for globular
      proteins, but is known to be more restricted for unfolded or intrinsically
      disordered proteins (IDPs). We have used ensembles of disordered structures from
      molecular dynamics simulations to investigate which structural properties cause
      deviations from the Guinier approximation at small scattering angles. We find
      that the deviation from the Guinier approximation is correlated with the polymer
      scaling exponent nu describing the unfolded ensemble. We therefore introduce an
      empirical, nu-dependent, higher-order correction term, to augment the standard
      Guinier analysis. We test the new fitting scheme using all-atom simulation data
      for several IDPs and experimental data for both an IDP and a destabilized mutant
      of a folded protein. In all cases tested, we achieve an accuracy of the inferred
      Rg within ~3% of the true Rg. The method is straightforward to implement and
      extends the range of validity to a maximum qRg of ~2 versus ~1.1 for Guinier
      analysis. Compared with the Guinier or Debye approaches, our method allows data
      from wider angles with lower noise to be used to analyze scattering data
      accurately. In addition to Rg, our fitting scheme also yields estimates of the
      scaling exponent nu in excellent agreement with the reference nu determined from
      the underlying molecular ensemble.

PMID- 29571690
TI  - Revisiting Prior Studies-Is There More There?

PMID- 29571691
TI  - Editorial Comment.

PMID- 29571692
TI  - Peer Review 2017.

PMID- 29571694
TI  - Reply by Authors.

PMID- 29571693
TI  - 2017 Journal of Urology Peer Reviewers.

PMID- 29571695
TI  - Re: Effect of Prior Focal Therapy on Perioperative, Oncologic and Functional
      Outcomes of Salvage Robotic Assisted Radical Prostatectomy: I. Nunes-Silva, E.
      Barret, V. Srougi, M. Baghdadi, P. Capogrosso, S. Garcia-Barreras, S. Kanso, R.
      Tourinho-Barbosa, A. Carneiro, R. Sanchez-Salas, F. Rozet, M. Galiano and X.
      Cathelineau J Urol 2017;198:1069-1076.

PMID- 29571696
TI  - Editorial Comment.

PMID- 29571697
TI  - Efficacy of non-surgical interventions on dynamic balance in patients with ankle
      instability: A network meta-analysis.
AB  - OBJECTIVES: To identify non-surgical treatments which were deemed to be more
      effective in improving dynamic postural control in patients with chronic ankle
      instability (CAI). DESIGN: Systematic review and random-effects network meta
      analysis. METHODS: We searched Scopus, CENTRAL, and PubMed until 26 August 2017.
      We used data from randomized trials comparing the results of different non
      surgical interventions for lateral CAI. We assessed dynamic postural control in
      terms of the star-excursion balance test in the posteromedial direction. We
      evaluated this outcome at the end of the rehabilitation protocols (i.e., short
      term) and 6months after treatment (i.e., medium term). We assessed the quality of
      the included studies with the Cochrane risk of bias tool and evaluated the
      quality of evidence from the network of interventions using the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
      RESULTS: Nineteen trials were eligible for inclusion in this systematic review. A
      4-6-week supervised balance training program and a 4-6-week strengthening
      rehabilitation protocol provided significant improvements compared to control (8
      studies, standardized mean difference [SMD] was -0.75, 95% CIs [-1.28 to -0.23]);
      and 2 studies, SMD was -1.2, 95% CIs [-2.36 to -0.08], respectively). A 6-week
      combined intervention that addressed balance and strength had the highest
      probability of being among the best treatments. However, the latter
      rehabilitation intervention was included in only one trial. CONCLUSIONS: The
      network meta-analysis showed that supervised balance training protocols and
      strengthening programs significantly improved dynamic balance in patients with
      CAI. A combination of these interventions may further increase the efficacy of
      non-surgical treatment options for the first-line management of CAI.

PMID- 29571698
TI  - Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic
      necrosis rate of musculoskeletal sarcoma?
AB  - PURPOSE: To identify quantitative perfusion parameters that are best associated
      with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3
      Tesla. METHODS: MR perfusion studies of 31 patients with a musculoskeletal
      sarcoma were retrospectively evaluated by two readers. There were 18 men and 13
      women with a mean age of 34.9+/-24.4 (standard deviation [SD] years) (range: 6-87
      years). All patients underwent carcinologic tumor resection less than 3 months
      after MR imaging. For all patients six perfusion parameters (three semi
      quantitative and three permeability parameters) were analyzed. The percentage of
      tumor necrosis was estimated using MR imaging. Perfusion data were compared
      between groups of tumors with different grades and necrosis ratios. Interobserver
      variability was calculated using intraclass correlation coefficient (ICC).
      RESULTS: Interobserver variability among the perfusion parameters was good to
      excellent (ICC: 0.72-0.9). The area under the curve and maximum slope values
      showed a significant association with the degree of tumor necrosis (P=0.02-0.04).
      When tumors with low necrosis ratios were compared to those with high ratios the
      former parameter was 80% lower. In the same groups, the imaging necrosis index
      was 56.9-59.8% higher in patients with grade 2 necrosis (P=0.01). Extracellular
      space volume (Ve) was 31.4% to 55.8% lower in tumors with high grade while the
      backflow constant (Kep) was 33.6% to 40.1%% higher in tumors with high grade.
      CONCLUSION: Semi-quantitative MR perfusion parameters have an excellent
      reproducibility and are associated with the degree of histologic tumor necrosis
      in musculoskeletal sarcomas. The utility of permeability parameters for
      determining tumor grade needs further investigations.

PMID- 29571699
TI  - Diffusion-weighted magnetic resonance imaging of extraocular muscles in patients
      with Grave's ophthalmopathy using turbo field echo with diffusion-sensitized
      driven-equilibrium preparation.
AB  - PURPOSE: The purpose of this study was to correlate diffusivity of extraocular
      muscles, measured by three-dimensional turbo field echo (3DTFE) magnetic
      resonance (MR) imaging using diffusion-sensitized driven-equilibrium preparation,
      with their size and activity in patients with Grave's ophthalmopathy. MATERIALS
      AND METHODS: Twenty-three patients with Grave's ophthalmopathy were included.
      There were 17 women and 6 men with a mean age of 55.8+/-12.6 (SD) years (range:
      26-83 years). 3DTFE with diffusion-sensitized driven-equilibrium MR images were
      obtained with b-values of 0 and 500s/mm2. The apparent diffusion coefficient
      (ADC) of extraocular muscles was measured on coronal reformatted MR images.
      Signal intensities of extraocular muscles on conventional MR images were compared
      to those of normal-appearing white matter, and cross-sectional areas of the
      muscles were also measured. The clinical activity score was also evaluated.
      Statistical analyses were performed with Pearson correlation and Mann-Whitney U
      tests. RESULTS: On 3DTFE with diffusion-sensitized driven-equilibrium
      preparation, the mean ADC of the extraocular muscles was 2.23+/-0.37 (SD)*10
      3mm2/s (range: 1.70*10-3-3.11*10-3mm2/s). There was a statistically significant
      moderate correlation between ADC and the size of the muscles (r=0.61). There were
      no statistically significant correlations between ADC and signal intensity on
      conventional MR and the clinical activity score. CONCLUSION: 3DTFE with diffusion
      sensitized driven-equilibrium preparation technique allows quantifying
      diffusivity of extraocular muscles in patients with Grave's ophthalmopathy. The
      diffusivity of the extraocular muscles on 3DTFE with diffusion-sensitized driven
      equilibrium preparation MR images moderately correlates with their size.

PMID- 29571700
TI  - Effect of cannabis and tobacco on emphysema in patients with spontaneous
      pneumothorax.
AB  - PURPOSE: To compare imaging findings on thoracic computed tomography (CT)
      examination in patients with primary spontaneous pneumothorax (SP), depending on
      their tobacco and/or cannabis consumption. MATERIALS AND METHODS: A total of 83
      patients who had thoracic CT for primary SP were prospectively included. There
      were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The
      patients were further categorized into three groups according to their smoking
      habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32
      were tobacco and cannabis smokers. CT examinations were retrospectively reviewed
      for the presence of blebs, centrilobular and paraseptal emphysema and lung
      nodules in each group for comparison. RESULTS: Emphysema was detected in 43/85
      patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38
      patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the
      tobacco and cannabis smokers, with no difference between tobacco only and tobacco
      and cannabis smokers. No differences in type and location of emphysema was found
      between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis
      smokers with emphysema were significantly younger than tobacco only smokers with
      emphysema (35 vs. 46 years, respectively) (P=0.009). CONCLUSION: The prevalence
      of emphysema visible on CT is not different between tobacco and tobacco/cannabis
      smokers, however, it occurs at a younger age in tobacco and cannabis smokers.
      This result suggests that cannabis, when added to tobacco, may lead to emphysema
      at a younger age.

PMID- 29571701
TI  - Edaravone in the treatment of amyotrophic lateral sclerosis.

PMID- 29571702
TI  - Competing trends of ROS and RNS-mediated protein modifications during hypoxia as
      an alternate mechanism of NO benefits.
AB  - Hypoxia, especially altitude associated hypoxia is known to cause severe
      physiological alterations and life-threatening conditions. Impaired redox balance
      along with oxidative stress, protein carbonylation and instigation of apoptotic
      events are common sub-cellular events that follow the hypoxic insult. The role of
      nitric oxide (NO) is very dynamic and versatile in preventing the ill effects of
      hypoxia vis-a-vis reacting with oxidative species and causing protein
      nitrosylation. Although several mechanisms of NO-mediated cytoprotection are
      known during hypoxic insult, limited pieces of evidence are available to support
      the relationship between two downstream events of oxidative stress, protein
      carbonylation (caused by carbonyl; CO radical) and protein
      nitrosylation/nitration (caused by NO/peroxynitrite; ONOO radical). In this
      study, we investigated an entirely new aspect of NO protection in hypoxia
      involving crosstalk between carbonylation and nitrosylation. Using standard NO
      inhibitor l-NAME and simulated hypoxic conditions in hypoxia-sensitive cell line
      H9c2, we evaluated the levels of radicals, cell death, mitochondrial membrane
      potential, levels of protein nitrosylation, protein nitration and carbonylation
      and glutathione content. The results were then carefully analyzed in light of NO
      bioavailability. Our study shows that reducing NO during hypoxia caused cell
      death via the increased degree of carbonylation in proteins. This provides a new
      aspect of NO benefits which furthers opens new possibilities to explore potential
      mechanisms and effects of cross-talk between nitrosylation, protein nitration and
      carbonylation, especially through some common antioxidant mediators such as
      glutathione and thioredoxin.

PMID- 29571703
TI  - Isolation and molecular characterization of a relapsing fever Borrelia recovered
      from Ornithodoros rudis in Brazil.
AB  - In South America, early reports from more than 50 years ago incriminated
      Ornithodoros rudis as vector of Borrelia venezuelensis, an agent of tick-borne
      relapsing fever (TBRF). Herein we report the rediscovery of O. rudis by means of
      morphological, biological and molecular analyses, which also comprise the first
      report of this tick species in Brazil. Phylogenetic analysis using partial
      fragments of mitochondrial 16S rRNA gene suggested that O. rudis forms a
      monophyletic group with Ornithodoros erraticus. By using laboratory rodents as
      hosts, we isolated a relapsing fever Borrelia from an infected O. rudis female.
      Phylogenetic analysis inferred from the rrs, flaB, and glpQ genes of Borrelia
      spp. placed the spirochete harbored by O. rudis closely related to Borrelia
      turicatae. Until further genetic evidence is not obtained we are referring to
      this O. rudis spirochete as B. venezuelensis. This is the first in vitro
      isolation of a TBRF Borrelia from South America. The presence of O. rudis in
      Brazil should not be overlooked, since this tick has been historically implicated
      in human cases of TBRF in Colombia, Panama, and Venezuela. This study provides
      new reports of O. rudis and B. venezuelensis after decades of scientific silence
      on these agents.

PMID- 29571704
TI  - Method development and optimization for the determination of benzene, toluene,
      ethylbenzene and xylenes in water at trace levels by static headspace extraction
      coupled to gas chromatography-barrier ionization discharge detection.
AB  - Benzene, toluene, ethylbenzene, and xylenes, more commonly named BTEX, represent
      one of the most ubiquitous and hazardous groups of atmospheric pollutants. The
      goal of our research was the trace quantification of BTEX in water by using a new
      simple, low-cost, and accurate method, based on headspace (HS) extraction and gas
      chromatography (GC) coupled to barrier ionization discharge detector (BID). This
      water application dealt with simple matrices without protein, fat, or humic
      material that adsorb target analytes, thus the external standard calibration was
      suitable to quantify each compound. The validation steps included the study of
      linearity, detection and quantification limits, and accuracy. LODs and LOQs
      varied from 0.159 to 1.845 MUg/L and from 0.202 to 2.452 MUg/L, respectively. The
      recovery was between 0.74 +/- 0.13 and 1.15 +/- 0.09; relative standard
      deviations (% RDSs) were less than 12.81% (n = 5) and 14.84% (n = 10). Also, GC
      performance was evaluated in term of efficiency, peak tailing and resolution.
      Preliminary results from practical applications to analyses of real samples are
      presented. The results indicate that static HS coupled to GC-BID is a successful
      method for BTEX analysis in water samples at the MUg/L levels, provided that
      hydrocarbons interference occur at similar concentration levels. GC-BID may
      become a routine reference method alongside the official analytical techniques
      for quality control purposes of contaminated waters. Moreover, the new method is
      amenable to automation by using commercial HS units.

PMID- 29571705
TI  - Optimal human and system performance during neonatal resuscitation.
AB  - Performance in the delivery of care to sick neonates in need of resuscitation has
      long been defined primarily in terms of the extent of the knowledge possessed and
      hands-on skill demonstrated by physicians and other healthcare professionals.
      This definition of performance in neonatal resuscitation is limited by its focus
      solely on the human beings delivering care and a perceived set of the requisite
      skills to do so. This manuscript will expand the definition of performance to
      include all of the skill sets that humans must use to resuscitate newborns as
      well as the often complex systems in which those humans operate while delivering
      that care. It will also highlight how the principles of human factors and
      ergonomics can be used to enhance human and system performance during patient
      care. Finally, it will describe the role of simulation and debriefing in the
      assessment of human and system performance.

PMID- 29571706
TI  - Prophylactic and early targeted treatment of patent ductus arteriosus.
AB  - Treatment of a haemodynamically significant patent ductus arteriosus (PDA) in the
      very preterm infant has been an accepted approach for several decades. However,
      the rationale for closure of PDA has recently been challenged due to reports of
      success with conservative approaches and the lack of evidence for longer-term
      benefits from treatment. In this article, we address an approach to assess
      treatment of those babies most likely to benefit.

PMID- 29571707
TI  - Synergistic approaches unraveling regulation and aggregation of intrinsically
      disordered beta-amyloids implicated in Alzheimer's disease.
AB  - Alzheimer's disease is a severe brain illness that causes vast numbers of nerve
      cells in the brain to die, driven by the production and deposition of amyloid
      beta (Abeta) peptides. Intrinsically disordered proteins (IDPs) generally lack
      stable structures and are abundant in nature. Abeta peptide is a well-known IDP
      with a wide range of oligomeric forms. Dysfunctions in Abeta lead to
      oligomerization, formation of fibrils, and neurodegenerative disorders or other
      forms of dementia. In this study, we used replica exchange molecular dynamics
      (REMD) to elucidate the roles of different osmolytes, particularly urea and
      trimethylamine N-oxide (TMAO), to study shifts in IDP populations. REMD samples
      the conformational space efficiently and at physiologically relevant
      temperatures, compared to conventional molecular dynamics that sample at a
      constant temperature. Urea is known to minimize the aggregation process, while
      TMAO is beneficial for its stabilizing action. The two osmolytes displayed
      characteristic effects on Abeta peptides and resulted in progressive modulation
      of conformations. The present study underlines the hypothesis of "modulation of
      conformational ensembles" to explain the regulation and aggregation of IDPs.

PMID- 29571708
TI  - High dimensional random walks can appear low dimensional: Application to
      influenza H3N2 evolution.
AB  - One important feature of the mammalian immune system is the highly specific
      binding of antigens to antibodies. Antibodies generated in response to one
      infection may also provide some level of cross immunity to other infections. One
      model to describe this cross immunity is the notion of antigenic space, which
      assigns each antibody and each virus a point in Rn. Past studies using
      hemagglutination data have suggested the dimensionality of antigenic space, n, is
      low. We propose that influenza evolution may be modeled as a Gaussian random
      walk. We then show that hemagluttination data would be consistent with a walk in
      very high dimensions. The discrepancy between our result and prior studies is due
      to the fact that random walks can appear low dimensional according to a variety
      of analyses including principal component analysis (PCA) and multidimensional
      scaling (MDS). A high dimensionality of antigenic space is of importance to
      modelers, as it suggests a smaller role for pre-existing immunity within the host
      population.

PMID- 29571709
TI  - Identifying essential proteins based on sub-network partition and prioritization
      by integrating subcellular localization information.
AB  - Essential proteins are important participants in various life activities and play
      a vital role in the survival and reproduction of living organisms. Identification
      of essential proteins from protein-protein interaction (PPI) networks has great
      significance to facilitate the study of human complex diseases, the design of
      drugs and the development of bioinformatics and computational science. Studies
      have shown that highly connected proteins in a PPI network tend to be essential.
      A series of computational methods have been proposed to identify essential
      proteins by analyzing topological structures of PPI networks. However, the high
      noise in the PPI data can degrade the accuracy of essential protein prediction.
      Moreover, proteins must be located in the appropriate subcellular localization to
      perform their functions, and only when the proteins are located in the same
      subcellular localization, it is possible that they can interact with each other.
      In this paper, we propose a new network-based essential protein discovery method
      based on sub-network partition and prioritization by integrating subcellular
      localization information, named SPP. The proposed method SPP was tested on two
      different yeast PPI networks obtained from DIP database and BioGRID database. The
      experimental results show that SPP can effectively reduce the effect of false
      positives in PPI networks and predict essential proteins more accurately compared
      with other existing computational methods DC, BC, CC, SC, EC, IC, NC.

PMID- 29571710
TI  - A 1D model of leukocyte adhesion coupling bond dynamics with blood velocity.
AB  - Cell adhesion on the vascular wall is a highly coupled process where blood flow
      and adhesion dynamics are closely linked. Cell dynamics in the vicinity of the
      vascular wall is driven mechanically by the competition between the drag force of
      the blood flow and the force exerted by the bonds created between the cell and
      the wall. Bonds exert a friction force. Here, we propose a mathematical model of
      such a competitive system, namely leukocytes whose capacity to create bonds with
      the vascular wall and transmigratory ability are coupled by integrins and
      chemokines. The model predicts that this coupling gives rise to a dichotomic cell
      dynamic, whereby cells switch from sliding to firm arrest, through non linear
      effects. Cells can then transmigrate through the wall. These predicted dynamic
      regimes are compared to in-vitro trajectories of leukocytes. We expect that
      competition between friction and drag force in particle dynamics (such as shear
      stress-controlled nanoparticle capture) can lead to similar dichotomic mode.

PMID- 29571712
TI  - Frequency-specific attentional modulation in human primary auditory cortex and
      midbrain.
AB  - Paying selective attention to an audio frequency selectively enhances activity
      within primary auditory cortex (PAC) at the tonotopic site (frequency channel)
      representing that frequency. Animal PAC neurons achieve this 'frequency-specific
      attentional spotlight' by adapting their frequency tuning, yet comparable
      evidence in humans is scarce. Moreover, whether the spotlight operates in human
      midbrain is unknown. To address these issues, we studied the spectral tuning of
      frequency channels in human PAC and inferior colliculus (IC), using 7-T
      functional magnetic resonance imaging (FMRI) and frequency mapping, while
      participants focused on different frequency-specific sounds. We found that shifts
      in frequency-specific attention alter the response gain, but not tuning profile,
      of PAC frequency channels. The gain modulation was strongest in low-frequency
      channels and varied near-monotonically across the tonotopic axis, giving rise to
      the attentional spotlight. We observed less prominent, non-tonotopic spatial
      patterns of attentional modulation in IC. These results indicate that the
      frequency-specific attentional spotlight in human PAC as measured with FMRI
      arises primarily from tonotopic gain modulation, rather than adapted frequency
      tuning. Moreover, frequency-specific attentional modulation of afferent sound
      processing in human IC seems to be considerably weaker, suggesting that the
      spotlight diminishes toward this lower-order processing stage. Our study sheds
      light on how the human auditory pathway adapts to the different demands of
      selective hearing.

PMID- 29571711
TI  - Curcumin plays neuroprotective roles against traumatic brain injury partly via
      Nrf2 signaling.
AB  - Traumatic brain injury (TBI), which leads to high mortality and morbidity, is a
      prominent public health problem worldwide with no effective treatment. Curcumin
      has been shown to be beneficial for neuroprotection in vivo and in vitro, but the
      underlying mechanism remains unclear. This study determined whether the
      neuroprotective role of curcumin in mouse TBI is dependent on the NF-E2-related
      factor (Nrf2) pathway. The Feeney weight-drop contusion model was used to mimic
      TBI. Curcumin was administered intraperitoneally 15 min after TBI induction, and
      brains were collected at 24 h after TBI. The levels of Nrf2 and its downstream
      genes (Hmox-1, Nqo1, Gclm, and Gclc) were detected by Western blot and qRT-PCR at
      24 h after TBI. In addition, edema, oxidative damage, cell apoptosis and
      inflammatory reactions were evaluated in wild type (WT) and Nrf2-knockout (Nrf2
      KO) mice to explore the role of Nrf2 signaling after curcumin treatment. In wild
      type mice, curcumin treatment resulted in reduced ipsilateral cortex injury,
      neutrophil infiltration, and microglia activation, improving neuron survival
      against TBI-induced apoptosis and degeneration. These effects were accompanied by
      increased expression and nuclear translocation of Nrf2, and enhanced expression
      of antioxidant enzymes. However, Nrf2 deletion attenuated the neuroprotective
      effects of curcumin in Nrf2-KO mice after TBI. These findings demonstrated that
      curcumin effects on TBI are associated with the activation the Nrf2 pathway,
      providing novel insights into the neuroprotective role of Nrf2 and the potential
      therapeutic use of curcumin for TBI.

PMID- 29571713
TI  - Auditory prediction cues motor preparation in the absence of movements.
AB  - There is increasing evidence for integrated representation of sensory and motor
      information in the brain, and that seeing or hearing action-related stimuli may
      automatically cue the movements required to respond to or produce them. In this
      study we tested whether anticipation of tones in a known melody automatically
      activates corresponding motor representations in a predictive way, in preparation
      for potential upcoming movements. Therefore, we trained 20 non-musicians (8 men,
      12 women) to play a simple melody. Then, while they passively listened to the
      learned or unlearned melodies, we applied single pulse transcranial magnetic
      stimulation (TMS) over M1 to measure motor evoked potentials from the associated
      finger muscle either preceding or following the onset of individual tones. Our
      results show that listening to the learned melody increased corticospinal
      excitability for specific finger muscles before tone onset. This demonstrates
      that predictable auditory information can activate motor representations in an
      anticipatory muscle-specific manner, even in the absence of intention to move.
      This suggests that the motor system is involved in the prediction of sensory
      events, likely based on auditory-parietal-prefrontal feedforward/feedback loops
      that automatically prepare predictable sound-related actions independent of
      actual execution and the associated auditory feedback. Overall, we propose that
      multimodal forward models of upcoming sounds and actions support motor
      preparation, facilitate error detection and correction, and guide perception.

PMID- 29571714
TI  - The chaotic morphology of the left superior temporal sulcus is genetically
      constrained.
AB  - The asymmetry of the superior temporal sulcus (STS) has been identified as a
      species-specific feature of the human brain. The so-called superior temporal
      asymmetrical pit (STAP) area is observed from the last trimester of gestation
      onwards and is far less pronounced in the chimpanzee brain. This asymmetry is
      associated with more frequent sulcal interruptions, named plis de passage (PPs),
      leading to the irregular morphology of the left sulcus. In this paper, we aimed
      to characterize the variability, asymmetry, and heritability of these
      interruptions in the STS in comparison with the other main sulci. We developed an
      automated method to extract PPs across the cortex based on a highly reproducible
      grid of sulcal pits across individuals, which we applied to a subset of Human
      Connectome Project (HCP) subjects (N = 820). We report that only a few PPs across
      the cortex are genetically constrained, namely in the collateral, postcentral and
      superior temporal sulci and the calcarine fissure. Moreover, some PPs occur more
      often in one hemisphere than the other, namely in the precentral, postcentral,
      intraparietal sulci, as well as in both inferior and superior temporal sulci.
      Most importantly, we found that only the interruptions within the STAP region are
      both asymmetric and genetically constrained. Because this morphological pattern
      is located in an area of the left hemisphere related to speech, our results
      suggest structural constraints on the architecture of the linguistic network.

PMID- 29571715
TI  - 3D conditional generative adversarial networks for high-quality PET image
      estimation at low dose.
AB  - Positron emission tomography (PET) is a widely used imaging modality, providing
      insight into both the biochemical and physiological processes of human body.
      Usually, a full dose radioactive tracer is required to obtain high-quality PET
      images for clinical needs. This inevitably raises concerns about potential health
      hazards. On the other hand, dose reduction may cause the increased noise in the
      reconstructed PET images, which impacts the image quality to a certain extent. In
      this paper, in order to reduce the radiation exposure while maintaining the high
      quality of PET images, we propose a novel method based on 3D conditional
      generative adversarial networks (3D c-GANs) to estimate the high-quality full
      dose PET images from low-dose ones. Generative adversarial networks (GANs)
      include a generator network and a discriminator network which are trained
      simultaneously with the goal of one beating the other. Similar to GANs, in the
      proposed 3D c-GANs, we condition the model on an input low-dose PET image and
      generate a corresponding output full-dose PET image. Specifically, to render the
      same underlying information between the low-dose and full-dose PET images, a 3D U
      net-like deep architecture which can combine hierarchical features by using skip
      connection is designed as the generator network to synthesize the full-dose
      image. In order to guarantee the synthesized PET image to be close to the real
      one, we take into account of the estimation error loss in addition to the
      discriminator feedback to train the generator network. Furthermore, a
      concatenated 3D c-GANs based progressive refinement scheme is also proposed to
      further improve the quality of estimated images. Validation was done on a real
      human brain dataset including both the normal subjects and the subjects diagnosed
      as mild cognitive impairment (MCI). Experimental results show that our proposed
      3D c-GANs method outperforms the benchmark methods and achieves much better
      performance than the state-of-the-art methods in both qualitative and
      quantitative measures.

PMID- 29571716
TI  - Mapping working memory retrieval in space and in time: A combined
      electroencephalography and electrocorticography approach.
AB  - In this study, we investigated the time course and neural correlates of the
      retrieval process underlying visual working memory. We made use of a rare dataset
      in which the same task was recorded using both scalp electroencephalography (EEG)
      and Electrocorticography (ECoG), respectively. This allowed us to examine with
      great spatial and temporal detail how the retrieval process works, and in
      particular how the medial temporal lobe (MTL) is involved. In each trial,
      participants judged whether a probe face had been among a set of recently studied
      faces. With a method that combines hidden semi-Markov models and multivariate
      pattern analysis, the neural signal was decomposed into a sequence of latent
      cognitive stages with information about their durations on a trial-by-trial
      basis. Analyzed separately, EEG and ECoG data yielded converging results on
      discovered stages and their interpretation, which reflected 1) a brief pre
      attention stage, 2) encoding the stimulus, 3) retrieving the studied set, and 4)
      making a decision. Combining these stages with the high spatial resolution of
      ECoG suggested that activity in the temporal cortex reflected item familiarity in
      the retrieval stage; and that once retrieval is complete, there is active
      maintenance of the studied face set in the decision stage in the MTL. During this
      same period, the frontal cortex guides the decision by means of theta coupling
      with the MTL. These observations generalize previous findings on the role of MTL
      theta from long-term memory tasks to short-term memory tasks.

PMID- 29571717
TI  - Simultaneous scalp recorded EEG and local field potentials from monkey ventral
      premotor cortex during action observation and execution reveals the contribution
      of mirror and motor neurons to the mu-rhythm.
AB  - The desynchronization of alpha and beta oscillations (mu rhythm) in the central
      scalp EEG during action observation and action execution is thought to reflect
      neural mirroring processes. However, the extent to which mirror neurons (MNs) or
      other populations of neurons contribute to such EEG desynchronization is still
      unknown. Here, we provide the first evidence that, in the monkey, the neuronal
      activity recorded from the ventral premotor cortex (PMv) strongly contributes to
      the EEG changes occurring in the beta band over central scalp electrodes, during
      executed and observed actions. We simultaneously recorded scalp EEG and
      extracellular activity, Multi Unit Activity (MUA) and Local Field Potentials
      (LFP), from area F5 of two macaques executing and observing grasping actions. We
      found that MUA highly correlates with an increase in high gamma LFP power and,
      interestingly, such LFP power increase also correlates to EEG beta - and in part
      also to alpha - desynchronization. In terms of timing of signal changes, the
      increase in high gamma LFP power precedes the EEG desynchronization, during both
      action observation and execution, thus suggesting a causal role of PMv neuronal
      activity in the modulation of the alpha and beta mu-rhythm. Lastly, neuronal
      signals from deeper layers of PMv exert a greater contribution than superficial
      layers to the EEG beta rhythm modulation, especially during the motor task. Our
      findings have clear implications for EEG studies in that they demonstrate that
      the activity of different populations of neurons in PMv contribute to the
      generation of the mu-rhythm.

PMID- 29571718
TI  - C-reactive protein response patterns after antibiotic treatment among children
      with scalds.
AB  - BACKGROUND: Scalds are the most common cause of burns in children, yet there is
      little information available about the inflammatory response. The aim of the
      study was to investigate the response to treatment with antibiotics among scalded
      children by following the C-reactive protein (CRP) concentration, procalcitonin
      (PCT) concentration, and white blood cell count (WCC) during the first two weeks
      after injury. METHODS: All children with scalds who presented to the Burn Centre
      during 2010-2016 were included in this retrospective study. All measurements of
      CRP, PCT, and WCC from the first 14days after injury were recorded, and each
      patient's maximum values during days 0-2, 3-7, and 8-14 were used for
      calculations. Multivariable regression for panel data was used to study the
      inflammatory response after antibiotic treatment. RESULTS: A total of 216
      children were included. C-reactive protein was 45mg/L (p<0.001) higher in the
      group treated with antibiotics, and decreased with 8.8mg/L per day over the
      studied time in this group, which was more than twice as fast as among the
      children who were not given antibiotics. CONCLUSION: The CRP response, among
      children with minor scalds treated with antibiotics, shows an appreciable rise
      during the first week of injury that subsided rapidly during the second week.

PMID- 29571719
TI  - Team clinical decision making in end-of-life care.

PMID- 29571720
TI  - Prenatal exposure to modafinil alters behavioural response to methamphetamine in
      adult male mice.
AB  - Modafinil is a psychostimulant drug prescribed for treatment of narcolepsy.
      However, it is used as a "smart drug" especially by young adults to increase
      wakefulness, concentration and mental performance. Therefore, it can also be used
      by women with childbearing potential and its developmental effects can become a
      concern. The aim of this study was to assess behavioural and immune effects of
      prenatal modafinil exposure in mice and to evaluate the reaction to
      methamphetamine exposure on these animals in adult age. Pregnant female mice were
      given either saline or modafinil (50 mg/kg orally) from gestation day (GD) 3 to
      GD 10 and then a challenge dose on GD 17. The male offspring were treated
      analogously at the age of 10 weeks with methamphetamine (2.5 mg/kg orally).
      Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile
      in the open field test were assessed in naive animals, after an acute and 8th
      modafinil dose and the challenge dose following a 7-day wash-out period. One
      month after completion of the behavioural study, the leukocyte phagocytosis was
      examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro.
      The modafinil prenatally exposed mice showed basal hypolocomotion, increased
      anxiety, lower locomotor effect of acute methamphetamine and increased
      vulnerability to behavioural sensitization. The leukocyte activity did not show
      significant differences. Prenatal modafinil exposure alters basal behavioural
      profile, decreases acute effect of methamphetamine and enhances vulnerability to
      development of behavioural sensitization at adulthood. This may lead to higher
      vulnerability to development of addiction.

PMID- 29571721
TI  - Relation of Platelet Indexes to Platelet Reactivity and Periprocedural Myocardial
      Infarction in Patients Who Underwent Percutaneous Coronary Angioplasty.
AB  - No comprehensive data are available on the role of platelet indexes (PI) in the
      periprocedural risk stratification of patients who underwent percutaneous
      coronary intervention (PCI). The aim of this study was to investigate the
      relation of PI to platelet reactivity (PR) and periprocedural myocardial
      infarction (PMI) in patients receiving PCI. A total of 502 PCI patients had
      preprocedural measurement of PI and PR, the latter assessed by VerifyNow P2Y12
      assay. Study end points were incidence of PMI and high platelet reactivity (HPR)
      according to tertiles of PI and evaluation of PI in HPR patients. Incidence of
      PMI in the overall population was 6.6%. Rates of PMI were not different in PI
      tertiles: platelet count (I: 6.0%, II: 7.1%, III: 6.5%; p = 0.74), mean platelet
      volume (MPV, I: 6.6%, II: 7.3%, III: 5.8%;p = 0.86), platelet distribution width
      (I: 7.2%, II: 7.2%, III: 5.8%;p = 0.74), and MPV/P ratio (I: 6.6%, II: 6.0%, III:
      7.1%; p = 0.91). The occurrence of PMI was significantly different in PR tertiles
      (I: 3%, II: 5.4%, III: 11.4%; p = 0.006). Platelet count and MPV/P ratio were
      significantly different in patients with and without HPR (221.8 +/- 58.6 * 103/uL
      vs207 +/- 59.4 * 103/uL, p = 0.008; 51.73 +/- 15.17 vs 56.7 +/- 18.3, p =
      0.002).In conclusion, this study showed no relation between PI and PMI in PCI
      patients but confirms the association of HPR with increased incidence of PMI;
      thus, PI seem to be not able to identify patients at higher periprocedural risk,
      but monitoring PR by a bedside assay remains a useful tool for risk
      stratification.

PMID- 29571722
TI  - Stroke and Cardiovascular Events After Ablation or Antiarrhythmic Drugs for
      Treatment of Patients With Atrial Fibrillation.
AB  - Catheter ablation and antiarrhythmic drugs (AADs) are the most common rhythm
      control strategies for atrial fibrillation (AF). Data comparing the rate of
      stroke and cardiovascular events between the treatment strategies are limited.
      Therefore, this observational study uses claims data to compare rate of
      cardiovascular hospitalization and stroke for patients with AF treated with
      ablation or AADs. Patients in the MarketScan dataset with AF between January 2010
      and December 2014 were categorized in the ablation group if an atrial catheter
      ablation was performed, or in the AAD group if a relevant AAD was prescribed for
      AF but no ablation was performed. One year of history was required, and the index
      event was selected as the most recent ablation or AAD prescription closest to
      January 1, 2013. A 2:1 propensity score match was performed for age, gender, co
      morbidities, and total medical cost in the year before index event. Outcomes
      included thromboembolic event (ischemic stroke, transient ischemic attack, or
      systemic embolism) and all cardiovascular hospitalizations. Of the 164,639
      patients in the AAD group, 29,456 were matched to the 14,728 ablation patients.
      There were no significant differences in age (64 +/- 10 in both groups), gender
      (58% male), or CHA2DS2-VASc score (3.2 +/- 1.3). Risk of hospitalization with
      primary diagnosis of thromboembolic event was 41% greater in the AADs group (p <
      0.001), and cardiovascular hospitalizations were 13% more likely (p < 0.001). In
      conclusion, patients treated with catheter ablation of AF have lower risk of
      thromboembolic events and cardiovascular hospitalizations than a matched cohort
      of patients managed with AADs.

PMID- 29571723
TI  - Phytochemical profiling and antiviral activity of Ajuga bracteosa, Ajuga
      parviflora, Berberis lycium and Citrus lemon against Hepatitis C Virus.
AB  - Hepatitis C is a serious health issue and cause liver disorders in millions of
      people. Available therapeutic agents require long term administration with
      numerous side effects. Therefore, there is a dire need to find alternative
      treatment options for this disease. Since ancient times, medicinal plants are
      widely used to cure various diseases with no or less harmful effects. Therefore,
      this study was designed to find out phytochemicals and investigate antiviral
      activity of methanol extract of Ajuga bracteosa, Ajuga parviflora, Berberis
      lycium and Citrus lemon against Hepatitis C Virus (HCV infection). Phytochemical
      analysis of the plant extract was performed using various chemical tests.
      Toxicity of the plant extract was determined against using trypan blue exclusion
      method. Antiviral activity of the selected plant extract was find out against HCV
      infected HepG2 cells. For this purpose, HepG2 cells were seeded with HCV positive
      and negative serum and nontoxic doses of plant extract for 24 and 48 h. After
      this RNA was extracted and viral load was determined using Real-time PCR.
      Phytochemical analysis showed the presence of flavonoids and phenols in all plant
      extracts while amino acids, alkaloids and tannins were present in B. lycium and
      saponins were detected in C. lemon. Toxicity assay showed that all plant extracts
      were nontoxic at maximum concentration of 200 MUg/ml except B. lycium, which
      showed mild toxicity at 40 MUg/ml and were extremely toxic at 60 MUg/ml and above
      doses. Real-time PCR quantitation result revealed that after 24 h treatments A.
      parviflora showed highest antiviral activity, followed by A. bracteosa, while B.
      lycium extract had low (35%) and C. lemon has no antiviral effects. The 48 h
      treatments showed an increase antiviral activity by A. bracteosa followed by A.
      parviflora and B. lycium while C. lemon showed negative effect. Our results
      depicted that mentioned plants might be used as an alternative therapeutic regime
      or in combination with existing treatments against HCV.

PMID- 29571724
TI  - Puerarin prevents LPS-induced acute lung injury via inhibiting inflammatory
      response.
AB  - Acute lung injury (ALI) is a critical illness syndrome with high morbidity and
      mortality in patients. Inflammation has been known to be involved in the
      development of ALI. The purpose of this study was to investigate the effect of
      puerarin on lipopolysaccharide (LPS)-induced ALI in mice. The pro-inflammatory
      cytokines TNF-alpha, IL-6 and IL-1beta were determined by ELISA. Western blot
      analysis was used for detecting the expression of NF-kappaB, IkappaBalpha, and
      LXRalpha. And myeloperoxidase (MPO) activity, lung wet/dry (W/D) ratio, and
      histopathological examination were also detected in lung tissues. The results
      showed that puerarin significantly inhibited LPS-stimulated MPO activity in lung
      tissues. Meanwhile, puerarin attenuated lung histopathological changes and lung
      wet/dry (W/D) ratio. We also found that the expression of pro-inflammatory
      cytokines, TNF-alpha, IL-6 and IL-1beta were inhibited by puerarin. Puerarin also
      inhibited LPS-induced TNF-alpha in RAW264.7 cells and IL-8 in A549 cells. From
      the results of western blotting, puerarin significantly suppressed LPS-stimulated
      NF-kappaB activation. And the expression of LXRalpha was dose-dependently
      increased by treatment of puerarin. The inhibition of puerarin on TNF-alpha
      production in RAW264.7 cells and IL-8 production in A549 cells were blocked by
      LXRalpha inhibitor geranylgeranyl pyrophosphate (GGPP). These results suggested
      that puerarin attenuated ALI by activating LXRalpha, which subsequently inhibited
      LPS-induced inflammatory response.

PMID- 29571726
TI  - Dyspepsia and Wilkie syndrome, an uncommon cause, but often forgotten.

PMID- 29571725
TI  - Attenuation of quorum sensing regulated virulence and biofilm development in
      Pseudomonas aeruginosa PAO1 by Diaporthe phaseolorum SSP12.
AB  - In recent years, Pseudomonas aeruginosa PAO1 emerged as the significant
      pathogenic microorganism in majority of the hospital-acquired infections due to
      its resistance to the conventional antibiotics by virtue of its highly organized
      quorum sensing and associated biofilm formation. In the present study, quorum
      sensing attenuation potential of Diaporthe phaseolorum SSP12 extract was
      investigated against P. aeruginosa PAO1 amply supported by molecular docking
      studies. D. phaseolorum SSP12 extract significantly inhibited the production of
      LasI/R mediated LasA protease, LasB elastase and chitinase with 66.52 +/- 5.41,
      71.26 +/- 4.58 and 61.16 +/- 4.28% of inhibition respectively at a concentration
      of 750 MUg mL-1. In addition, RhlI/R mediated production of pyocyanin,
      exopolysaccharides and rhamnolipids were also down-regulated by 74.71 +/- 3.97,
      66.41 +/- 3.62 and 63.75 +/- 3.76% respectively on treatment with sub-MIC
      concentration of D. phaseolorum SSP12. The light, fluorescence and confocal laser
      scanning microscopic (CLSM) analysis confirmed the significant disruption in
      biofilm formation. The presence of bioactive constituents such as phenyl
      ethylalcohol, 2, 4-di-tert-butylphenol, fenaclon, 1, 4-phenylenediacetic acid,
      and benzyl hydrazine in D. phaseolorum SSP12 extract was evident from Gas
      chromatography-mass spectrophotometric (GC-MS) analysis. From the in silico
      molecular docking studies, fenaclon and 2, 4-di-tert-butylphenol competitively
      binds to QS receptors LasR and RhlR and alters the binding of its cognate ligands
      and modulates the expression of virulence phenotypes. The promising anti quorum
      sensing efficacy of D. phaseolorum SSP12 extract suggested new avenues for
      development of anti-infective drugs from fungal derived metabolites to counteract
      the problems associated with conventional antibiotic therapies.

PMID- 29571728
TI  - Giant left ventricular thrombus embolism into the abdominal aorta.

PMID- 29571727
TI  - Intracardiac tromboembolism during liver transplantation.
AB  - We describe a case of intraoperative cardiac trombosis during orthotopic liver
      transplant surgery that resulted in intraoperative death. By using
      transesophageal echocardiography, the cause of the descompensation of the patient
      could be determined and the mechanism of trombus migration from thrombi from the
      venous circulation to the left heart was accurately observed.

PMID- 29571729
TI  - Quality and safety in endovascular therapy for acute ischemic stroke.

PMID- 29571730
TI  - Hybrid Coronary Revascularization Versus On-Pump Coronary Artery Bypass Grafting.
AB  - BACKGROUND: Hybrid coronary revascularization (HCR) is an evolving coronary
      revascularization strategy for the treatment of multivessel coronary artery
      disease. We provide a comparative analysis to conventional on-pump coronary
      artery bypass graft surgery (CABG) with long-term follow-up. METHODS: We included
      all double on-pump CABG (n = 682) and HCR (147 robotic-assisted minimally
      invasive bypass grafts of the left internal thoracic artery to the left anterior
      descending coronary artery and percutaneous coronary intervention to one of the
      non-left anterior descending coronary artery vessels) performed in our
      institution between March 2004 and November 2015. We performed an adjusted
      analysis using inverse-probability weighting based on the propensity score of
      receiving either on-pump CABG or HCR. RESULTS: In the adjusted analysis, there
      was no statistically significant difference in the incidence of reexploration for
      bleeding, perioperative myocardial infarction, stroke, need for hemodialysis,
      blood transfusion rate, prolonged mechanical ventilation, and intensive care unit
      length of stay. Hybrid coronary revascularization was associated with lower
      inhospital mortality (CABG 1.3%, HCR 0%, p = 0.008), and shorter mean (+/- SD)
      hospital length of stay (CABG 6.7 +/- 4.7 days, HCR 4.5 +/- 2.1 days, p < 0.001).
      After a median follow-up period of 70 months (range, 37 to 106) for the CABG
      group and 96 months (range, 53 to 114) for the HCR group, there was no
      significant difference in survival (CABG 92%, HCR 97%, p = 0.13) or freedom from
      any form of revascularization (CABG 93%, HCR 91%, p = 0.27). Hybrid coronary
      revascularization was superior in freedom from angina (CABG 70%, HCR 91%, p <
      0.001). CONCLUSIONS: For selected patients, HCR is associated with a faster
      postoperative recovery as well as similar short-term and long-term outcomes when
      compared with standard on-pump CABG.

PMID- 29571731
TI  - HMGB1 mediates HAdV-7 infection-induced pulmonary inflammation in mice.
AB  - Human adenovirus (HAdV) is a common respiratory pathogen in children, with no
      safe and effective treatment currently available. HAdV type 7 (HAdV-7), in
      particular, causes severe pediatric pneumonia with a high incidence of sequelae
      and mortality. Clinical data and animal experiments suggest that HAdV-7-induced
      pneumonia promotes cell necrosis, releasing a large number of inflammatory
      mediators. In recent years, the high mobility group box-1 (HMGB1) protein,
      released by necrotic cells, has been shown to play important roles in several
      viral infections. Here, we show that HMGB1 levels gradually increased in the
      media supernatants of HAdV-7 infected A549 cells, starting at 12 h post
      infection. In vivo, HMGB1 levels in BALF and mRNA levels in lung tissues
      significantly increased after 3 days of HAdV-7 infection. Among the HMGB1
      receptor genes, TLR-4 and TLR-9 expression increased, and so did the receptor for
      advanced glycation end-products (RAGE). Interestingly, NF-kappaB levels also
      increased concomitantly. Conversely, when HMGB1 was blocked, the pathological
      scores from lung tissues, inflammatory mediator levels, and viral copy number all
      were reduced significantly; in addition, HMGB1-related signaling pathway
      molecules, namely TLR-4, TLR-9, RAGE, and NF-kappaB were also reduced. We
      conclude that HMGB1 promotes HAdV-7 replication and signals through TLR-4, TLR-9,
      and RAGE receptors to activate NF-kappaB, stimulating the release of inflammatory
      mediators and contributing to adenoviral pathology. Thus, HMGB1 could be used as
      a therapeutic target in HAdV-7 infection.

PMID- 29571732
TI  - Induction of MEK/ERK activity by AZD8055 confers acquired resistance in
      neuroblastoma.
AB  - Mammalian target of rapamycin (mTOR) complex (mTORC) is frequently activated in
      diverse cancers. Although dual mTORC1/2 inhibitors are currently under
      development to treat various malignancies, the emergence of drug resistance has
      proven to be a major complication. AZD8055 is a novel, potent ATP-competitive and
      specific inhibitor of mTOR kinase activity, which blocks both mTORC1 and mTORC2
      activation. In this study, we acquired AZD8055-resistant neuroblastoma (NB) cell
      sublines by using prolonged stepwise escalation of AZD8055 exposure (4-12 weeks).
      Here we demonstrate that the AZD8055-resistant sublines (TGW-R and SMS-KAN-R)
      exhibited marked resistance to AZD8055 compared to the parent cells (TGW and SMS
      KAN). The cell cycle G1/S transition was advanced in resistant cells. In
      addition, the resistance against AZD8055 correlated with over-activation of
      MEK/ERK signaling pathway. Furthermore, combination of AZD8055 and MEK inhibitor
      U0126 enhanced the growth inhibition of resistant cells significantly in vitro
      and in vivo. In conclusion, these data show that targeting mTOR kinase and
      MEK/ERK signaling simultaneously might help to overcome AZD8055 resistance in NB.

PMID- 29571733
TI  - The guanine nucleotide-binding protein alpha subunit protein ChGnaq positively
      regulates Hsc70 transcription in Crassostrea hongkongensis.
AB  - Gnaq, one of Guanine nucleotide-binding protein alpha subunits, was isolated from
      cellular nucleus extracts of oyster Crassostrea hongkongensis gills with biotin
      labeled ChHsc70 promoter by means of DNA-affinity purification, and preliminarily
      identified with mass spectrometry analysis. ChGnaq mRNA depletion by RNAi
      technique led to clear reduction in ChHsc70 mRNA expression of C. hongkongensis
      hemocytes. Correspondently, ChGnaq over-expression in heterologous HEK293T cells
      correlated with elevated expression activation of ChHsc70 promoter. Quantitative
      real time PCR analysis showed that both ChHsc70 and ChGnaq transcriptions were
      responsive to external physical/chemical stresses by heat, CdCl2 and NP. This
      suggested a plausible association between ChHsc70 and ChGnaq in the stress
      induced genetic regulatory pathway. This study discovered a positively regulatory
      role of ChGnaq in controlling ChHsc70 transcription of C. hongkongensis, and
      conduced to a better understanding of the regulatory mechanisms in control of
      Hsc70 transcription.

PMID- 29571734
TI  - NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing
      inflammation response.
AB  - Diabetic retinopathy (DR) is the common cause of diabetic vascular complications.
      The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known
      as NALP1, inflammasome is the first member of the NLR family to be discovered,
      playing an important role in inflammatory response. However, its effect on DR
      development has not been reported. In the study, the wild type (WT) and NLRP1-/-
      mice were injected with streptozotocin (STZ) to induce DR. The results indicated
      that NLRP1-/- significantly increased bodyweight reduction and decreased blood
      glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in
      retinas. NLRP1-/- ameliorated retinal abnormalities in DR mice using H&E
      staining. In addition, attenuated avascular areas and neovascular tufts were also
      observed in NLRP1-/-/DR mice. The levels of pro-inflammatory cytokines in serum
      and retinas were highly induced in WT/DR mice, whereas being markedly reduced by
      NLRP1-/-. In addition, vascular endothelial growth factor (VEGF) and Iba1
      expressions induced by STZ in serum or retinas were significantly down-regulated
      in NLRP1-/-/DR mice. Consistently, NLRP1-/- attenuated ASC and Caspase-1
      expressions in retinas of DR mice. Compared to WT/DR group, NLRP1-/- markedly
      decreased retina p-nuclear factor-kappaB (NF-kappaB), interleukin-1beta (IL
      1beta) and IL-18 levels. And similar results were confirmed in vitro that
      suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose
      treated retinal ganglion cells. The results above indicated that the modulation
      of NLRP1 inflammasome might be a promising strategy for DR therapy.

PMID- 29571735
TI  - Regional up-regulation of NOX2 contributes to the differential vulnerability of
      outer hair cells to neomycin.
AB  - In hearing loss induced by aminoglycoside antibiotics, the outer hair cells
      (OHCs) in the basal turn are always more susceptible than OHCs in the apical
      turn, while the underlying mechanisms remain unknown. In this study, we reported
      that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage
      preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs
      among different turns, at a relatively low level. However, after neomycin
      treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in
      vitro studies demonstrated that inhibition of NOX2 significantly alleviated
      neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL
      staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that
      NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our
      study shows that regional up-expression of NOX2 and subsequent increase of ROS in
      OHCs of the basal turn is an important factor contributing to the vulnerability
      of OHCs there, which should shed light on the prevention of hearing loss induced
      by aminoglycoside antibiotics.

PMID- 29571736
TI  - Liraglutide attenuates NLRP3 inflammasome-dependent pyroptosis via regulating
      SIRT1/NOX4/ROS pathway in H9c2 cells.
AB  - The glucagon-like peptide-1 analog liraglutide has been proved to exert
      cardioprotective role via activating prosurvival pathways and suppressing
      inflammation. The activation of NLRP3 inflammasome plays an important role in
      ischemic injury. The effect of liraglutide on NLRP3 inflammasome-dependent
      pyroptosis remains unclear. In this study, we established a double stimulation
      model with TNF-alpha and hypoxia to mimic ischemic environment and to induce
      NLRP3 inflammasome activation in H9c2 cardiomyoblasts. Pretreatment with 100 nM
      liraglutide could efficiently inhibit TNF-alpha and hypoxia-induced inflammasome
      activation, as evidenced by the decreased expression of NLRP3, caspase-1 p20 and
      Gasdermin D N-terminal fragment. Meanwhile, the pyroptosis was also demonstrated
      to be suppressed, indicated by the increased cell viability and decreased lactate
      dehydrogenase release in the cells. Mechanistically, liraglutide reversed the
      level of SIRT1 and the selective SIRT1 inhibitor EX 527 significantly abolished
      the anti-pyroptosis role of liraglutide. Furthermore, liraglutide diminished the
      levels of ROS generation and NOX4 expression, which could also be blocked by EX
      527. Our results uncovered the anti-pyroptosis role of liraglutide in TNF-alpha
      and hypoxia-stimulated H9c2 cells, which was associated with SIRT1/NOX4/ROS
      pathway.

PMID- 29571737
TI  - Characterization of a non-phosphotransferase system for cis,cis-muconic acid
      production in Corynebacterium glutamicum.
AB  - Cis,cis-muconic acid (CCM) is a biochemical material that can be used for the
      production of various plastics and polymers and is particularly gaining attention
      as an adipic acid precursor for the synthesis of nylon-6,6. In the current study,
      the production of CCM was first attempted by introducing a newly developed
      protocatechuate (PCA) decarboxylase from Corynebacterium glutamicum 13032 to
      inha103, which completed the biosynthetic pathway therein. To improve CCM
      productivity, a phosphoenol pyruvate (PEP)-dependent phosphotransferase system
      (PTS) that consumed the existing glucose was developed, in the form of a strain
      with a non-PTS that did not consume PEP. To improve glucose uptake, we developed
      P25 strain, in which iolR (a transcriptional regulator gene) was additionally
      deleted. Strain P28, a P25 derivative expressing PCA decarboxylase, produced 4.01
      g/L of CCM, which was 14% more than that produced by the parental strain.
      Moreover, strains P29 and P30, with an active pentose phosphate pathway and
      overexpressing important genes (qsuB) in the metabolic pathway, produced 4.36 and
      4.5 g/L of CCM, respectively. Particularly, the yield per glucose in strain P30
      was similar to that of the fed-batch culture of Escherichia coli, which has the
      highest reported yield of 22% (mol/mol). These results are underpinned by the
      characteristics of the non-PTS with increased PEP availability and a strain with
      deletion of the iolR gene, which greatly increased glucose uptake.

PMID- 29571738
TI  - Determination of Interaction Parameters for Reversibly Self-Associating
      Antibodies: A Comparative Analysis.
AB  - Monoclonal antibodies (mAbs) represent a major class of biotherapeutics and are
      the fastest growing category of biologic drugs on the market. However, mAb
      development and formulation are often impeded by reversible self-association
      (RSA), defined as the dynamic exchange of monomers with native-state oligomers.
      Here, we present a comparative analysis of the self-association properties for 5
      IgG mAbs, under matched conditions and using orthogonal methods. Concentration
      dependent dynamic light scattering and sedimentation velocity studies revealed
      that the majority of mAbs examined exhibited weak to moderate RSA. However,
      because these studies were carried out at mAb concentrations in the mg/mL range,
      we also observed significant nonideality. Noting that nonideality frequently
      masks RSA and vice versa, we conducted direct boundary fitting of the
      sedimentation velocity data to determine stoichiometric binding models,
      interaction affinities, and nonideality terms for each mAb. These analyses
      revealed equilibrium constants from micromolar to millimolar and stoichiometric
      models from monomer-dimer to isodesmic. Moreover, even for those mAbs described
      by identical models, we observed distinct kinetics of self-association. The
      accuracy of the models and their corresponding equilibrium constants were
      addressed using sedimentation equilibrium and simulations. Overall, these results
      serve as the starting point for the comparative dissection of RSA mechanisms in
      therapeutic mAbs.

PMID- 29571739
TI  - Translational Pharmacokinetic/Pharmacodynamic Characterization and Target
      Mediated Drug Disposition Modeling of an Anti-Tissue Factor Pathway Inhibitor
      Antibody, PF-06741086.
AB  - Tissue factor pathway inhibitor (TFPI) exhibits multiple isoforms, which are
      known to present in multiple locations such as plasma, endothelium, and
      platelets. TFPI is an endogenous negative modulator of the coagulation pathway,
      and therefore, neutralization of TFPI function can potentially increase
      coagulation activity. A human monoclonal antibody, PF-06741086, which interacts
      with all isoforms of TFPI is currently being tested in clinic for treating
      hemophilia patients with and without inhibitors. To support clinical development
      of PF-06741086, pharmacokinetics (PK) and pharmacodynamics of PF-06741086 were
      characterized in monkeys. In addition, a mechanistic model approach was used to
      estimate PK parameters in monkeys and simulate PK profiles in human. The results
      show that PF-06741086 exhibited target-mediated drug disposition and had specific
      effects on various hemostatic markers including diluted prothrombin time,
      thrombin generation, and thrombin-antithrombin complex in monkeys after
      administration. The model-predicted and observed human exposures were compared
      retrospectively, and the result indicates that the exposure prediction was
      reasonable within less than 2-fold deviation. This study demonstrated in vivo
      efficacy of PF-06741086 in monkeys and the utility of a rational mechanistic
      approach to describe PK for a monoclonal antibody with complex target binding.

PMID- 29571740
TI  - Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil
      Hydrochloride.
AB  - Literature data relevant to the decision to waive in vivo bioequivalence testing
      for the approval of generic immediate release solid oral dosage forms of
      proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics
      Classification System (BCS) classification, experimental solubility and
      dissolution studies were also carried out. The antimalarial proguanil
      hydrochloride, effective via the parent compound proguanil and the metabolite
      cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil
      hydrochloride salt was shown to be highly soluble according to the U.S. Food and
      Drug Administration, World Health Organization, and European Medicines Agency
      guidelines, but data for permeability are inconclusive. Therefore, proguanil
      hydrochloride is conservatively classified as a BCS class 3 substance. In view of
      this information and the assessment of risks associated with a false positive
      decision, a BCS-based biowaiver approval procedure can be recommended for orally
      administered solid immediate release products containing proguanil hydrochloride,
      provided well-known excipients are used in usual amounts and provided the in
      vitro dissolution of the test and reference products is very rapid (85% or more
      are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to
      the current requirements for BCS-based biowaivers.

PMID- 29571741
TI  - Immunobiologically relevant level of aflatoxin B1 alters transcription of key
      functional immune genes, phagocytosis and survival of human dendritic cells.
AB  - The effects of naturally occurring levels of aflatoxin (AF) B1 on the expression
      of key molecules and function of dendritic cells (DCs) were investigated on human
      monocyte-derived DCs (MDDCs) by cell culture, RT-qPCR, and flow cytometry. An
      environmentally relevant level of AFB1 remarkably impaired the phagocytic
      capacity of MDDCs. Furthermore, AFB1 significantly affected the transcript levels
      of some key functional genes in MDDCs. It caused an up-regulation of key
      transcripts in cytochrome P450 (CYP) family, MyD88, NF-KB, TNF-alpha, TLR2, TLR4,
      COX-2, HLA-DR, CCR7, CD209, LFA3 and CD16. AFB1 down-regulated the expression of
      AhR, TGF-beta, CD11c and CD64 within 2-12 h post-exposure. In contrast, the
      transcription of some other key genes, including IL-10, IL-1beta, AKR7A2, GSTM1,
      IL-6. IL-8 and C5aR in post-AFB1 treated MDDCs was only slightly changed. The
      results indicate that an environmentally relevant level of AFB1 impairs the
      phagocytosis capacity of MDDCs and dysregulates the key functions in these
      pivotal immune cells. This could provide a mechanistic explanation for the
      observed in vivo immunotoxicity associated with this mycotoxin, and further
      emphasize the essential need for reduction of AFB1 levels in agricultural
      commodities.

PMID- 29571742
TI  - Family Interview to Enable Donation of Organs for Transplantation: Evidence-based
      Practice.
AB  - BACKGROUND: In this study we propose a theoretical and practical basis for the
      best practices for interviewing relatives of brain-dead eligible organ donors.
      METHODS: This investigation was a reflective study of the methodologic factors of
      the family interview that affect their decision regarding the donation of a
      deceased patient's organs for transplantation. The articles that formed the
      empirical basis of the trial were obtained from PubMed, which is a free-access
      tool of the MEDLINE database of the United States National Library of Medicine.
      Published articles that allowed us to reflect on evidence-based family interview
      practice were selected. RESULTS: Thirty-six scientific articles were used to
      guide our assessment the family interview, providing evidence for its adequate
      execution in view of the following prerequisites: When should the family
      interview be performed? Where should it be done? How many and which people should
      participate in the interview? Who should perform it? How should it be done?
      CONCLUSION: Scientific studies offer evidence to donation and transplantation
      specialists that can help them in their daily work regarding their interactions
      with relatives in the process of decisionmaking and family consent.

PMID- 29571743
TI  - Acute Inflammatory Syndrome Paradoxically Induced by De Novo Purine Inhibitors
      Synthesis Before Renal Transplantation: A Case Report and Review of the
      Literature.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) and mizoribine (MZR) are increasingly
      used as immunosuppressive agents for organ transplantation and chronic
      inflammation. We report a patient with rheumatoid arthritis who had an acute
      inflammatory syndrome triggered by preoperative immunosuppression therapy with
      both MMF and MZR. CASE REPORT: A 41-year-old woman with IgA nephropathy was
      referred to our department for living donor renal transplantation. She had
      rheumatoid arthritis that was adequately treated with prednisolone 5 mg once a
      day and salazosulfapyridine 2000 mg once a day. MMF 1000 mg twice a day was
      started for desensitization therapy. Three days later, the patient developed
      arthritis in the joints of her left hand and elevated inflammatory markers. On
      day 7, MMF was switched to MZR 150 mg 3 times a day. However, the symptoms
      extended to both shoulders and the joints of the right foot; MZR was
      discontinued. The arthritis and inflammatory markers improved. Two months later,
      the patient was rechallenged with MMF followed by MZR, resulting in a similar
      clinical course as previously. Tacrolimus (TAC) 3 mg twice a day and everolimus
      (EVL) 0.5 mg twice a day were introduced as alternative immunosuppressant
      therapies. No arthritis occurred. ABO-compatible living donor renal
      transplantation was successfully performed. The patient received TAC, EVL,
      prednisolone, rituximab, and basiliximab, and her postoperative course was
      uneventful without arthritis or rejection. At 9 months postoperatively, the serum
      creatinine was 0.79 mg/dL. CONCLUSIONS: Acute inflammatory syndrome is an
      extremely rare complication triggered by preoperative immunosuppression therapy.
      If antimetabolites cannot be used in immunologically high-risk patients,
      transplantation becomes very difficult. Clinicians should keep in mind this
      paradoxical reaction.

PMID- 29571744
TI  - The NC domain of HIV-1 Gag contributes to the interaction of Gag with TSG101.
AB  - BACKGROUND: HIV-1 Gag polyprotein orchestrates the assembly of viral particles.
      Its C-terminus consists of the nucleocapsid (NC) domain that interacts with RNA,
      and the p6 domain containing the PTAP motif that binds the cellular ESCRT factor
      TSG101 and ALIX. Deletion of the NC domain of Gag (GagNC) results in defective
      Gag assembly, a decrease in virus production and, thus probably affects
      recruitment of the ESCRT machinery. To investigate the role of GagNC in this
      recruitment, we analysed its impact on TSG101 and ALIX localisations and
      interactions in cells expressing Gag. METHODS: Cells expressing mCherry-Gag or
      derivatives, alone or together with eGFP-TSG101 or eGFP-ALIX, were analysed by
      confocal microscopy and FLIM-FRET. Chemical shift mapping between TSG101-UEV
      motif and Gag C-terminus was performed by NMR. RESULTS: We show that deletion of
      NC or of its two zinc fingers decreases the amount of Gag-TSG101 interacting
      complexes in cells. These findings are supported by NMR data showing chemical
      shift perturbations in the NC domain in- and outside - of the zinc finger
      elements upon TSG101 binding. The NMR data further identify a large stretch of
      amino acids within the p6 domain directly interacting with TSG101. CONCLUSION:
      The NC zinc fingers and p6 domain of Gag participate in the formation of the Gag
      TSG101 complex and in its cellular localisation. GENERAL SIGNIFICANCE: This study
      illustrates that the NC and p6 domains cooperate in the interaction with TSG101
      during HIV-1 budding. In addition, details on the Gag-TSG101 complex were
      obtained by combining two high resolution biophysical techniques.

PMID- 29571745
TI  - Differential effects on enzyme stability and kinetic parameters of mutants
      related to human triosephosphate isomerase deficiency.
AB  - Human triosephosphate isomerase (TIM) deficiency is a very rare disease, but
      there are several mutations reported to be causing the illness. In this work, we
      produced nine recombinant human triosephosphate isomerases which have the
      mutations reported to produce TIM deficiency. These enzymes were characterized
      biophysically and biochemically to determine their kinetic and stability
      parameters, and also to substitute TIM activity in supporting the growth of an
      Escherichia coli strain lacking the tim gene. Our results allowed us to rate the
      deleteriousness of the human TIM mutants based on the type and severity of the
      alterations observed, to classify four "unknown severity mutants" with altered
      residues in positions 62, 72, 122 and 154 and to explain in structural terms the
      mutation V231M, the most affected mutant from the kinetic point of view and the
      only homozygous mutation reported besides E104D.

PMID- 29571746
TI  - Oleuropein aglycone: A polyphenol with different targets against amyloid
      toxicity.
AB  - BACKGROUND: Many data highlight the benefits of the Mediterranean diet and its
      main lipid component, extra-virgin olive oil (EVOO). EVOO contains many phenolic
      compounds that have been found effective against several aging- and lifestyle
      related diseases, including neurodegeneration. Oleuropein, a phenolic secoiroid
      glycoside, is the main polyphenol in the olive oil. It has been reported that the
      aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid
      aggregation of a number of proteins/peptides involved in amyloid, particularly
      neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying
      protection against cognitive deterioration. METHODS: In this study, we carried
      out a cellular and biophysical study on the relationships between the effects of
      OleA on the aggregation and cell interactions of the D76N beta2-microglobulin
      (D76N b2m) variant associated with a familial form of systemic amyloidosis with
      progressive bowel dysfunction and extensive visceral amyloid deposits. RESULTS:
      Our results indicate that OleA protection against D76N b2m cytotoxicity results
      from i) a modification of the conformational and biophysical properties of its
      amyloid fibrils; ii) a modification of the cell bilayer surface properties of
      exposed cells. CONCLUSIONS: This study reveals that OleA remodels not only D76N
      b2m aggregates but also the cell membrane interfering with the misfolded proteins
      cell membrane association, in most cases an early event triggering amyloid
      mediated cytotoxicity. GENERAL SIGNIFICANCE: The data provided in the present
      article focus on OleA protection, featuring this polyphenol as a promising plant
      molecule useful against amyloid diseases.

PMID- 29571748
TI  - Structural basis of the signal transduction via transmembrane domain of the human
      growth hormone receptor.
AB  - BACKGROUND: Prior studies of the human growth hormone receptor (GHR) revealed a
      distinct role of spatial rearrangements of its dimeric transmembrane domain in
      signal transduction across membrane. Detailed structural information obtained in
      the present study allowed elucidating the bases of such rearrangement and
      provided novel insights into receptor functioning. METHODS: We investigated the
      dimerization of recombinant TMD fragment GHR254-294 by means of high-resolution
      NMR in DPC micelles and molecular dynamics in explicit POPC membrane. RESULTS: We
      resolved two distinct dimeric structures of GHR TMD coexisting in membrane
      mimicking micellar environment and providing left- and right-handed helix-helix
      association via different dimerization motifs. Based on the available mutagenesis
      data, the conformations correspond to the dormant and active receptor states and
      are distinguished by cis-trans isomerization of Phe-Pro266 bond in the
      transmembrane helix entry. Molecular dynamic relaxations of the structures in
      lipid bilayer revealed the role of the proline residue in functionally
      significant rearrangements of the adjacent juxtamembrane region supporting
      alternation between protein-protein and protein-lipid interactions of this region
      that can be triggered by ligand binding. Also, the importance of juxtamembrane SS
      bonding for signal persistency, and somewhat unusual aspects of transmembrane
      region interaction with water molecules were demonstrated. CONCLUSIONS: Two
      alternative dimeric structures of GHR TMD attributed to dormant and active
      receptor states interchange via allosteric rearrangements of transmembrane
      helices and extracellular juxtamembrane regions that support coordination between
      protein-protein and protein-lipid interactions. GENERAL SIGNIFICANCE: This study
      provides a holistic vision of GHR signal transduction across the membrane
      emphasizing the role of protein-lipid interactions.

PMID- 29571749
TI  - Detecting agitation and aggression in people with dementia using sensors-A
      systematic review.
AB  - Agitation and aggression are among the most challenging symptoms of dementia.
      Agitated persons with dementia can harm themselves, their caregivers, or other
      patients in a care facility. Automatic detection of agitation would be useful to
      alert caregivers so that appropriate interventions can be performed. The building
      blocks in the automatic detection of agitation and aggression are appropriate
      sensing platforms and generalized predictive models. In this article, we perform
      a systematic review of studies that use different types of sensors to detect
      agitation and aggression in persons with dementia. We conclude that actigraphy
      shows some evidence of correlation with incidences of agitation and aggression;
      however, multimodal sensing has not been fully evaluated for this purpose. Based
      on this systematic review, we provide guidelines and recommendations for future
      research directions in this field.

PMID- 29571747
TI  - Cdk5 suppression blocks SIRT1 degradation via the ubiquitin-proteasome pathway in
      Parkinson's disease models.
AB  - The NAD+-dependent protein deacetylase sirtuin 1 (SIRT1), a member of the sirtuin
      family, may have a neuroprotective effect in multiple neurodegenerative disorders
      such as Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic
      lateral sclerosis (ALS). Many studies have suggested that overexpression-induced
      or resveratrol-treated activation of SIRT1 could significantly ameliorate several
      neurodegenerative diseases in mouse models. However, the type of SIRT1, protein
      expression levels and underlying mechanisms remain unclear, especially in PD. In
      this study, the results demonstrated that SIRT1 knockout markedly worsened the
      movement function in MPTP-lesioned animal model of PD. SIRT1 expression was found
      to be markedly decreased not only in environmental factor PD models, neurotoxin
      MPP+-treated primary culture neurons and MPTP-induced mice but also in genetic
      factor PD models, overexpressed alpha-synuclein-A30PA53T SH-SY5Y stable cell line
      and hm2alpha-SYN-39 transgenic mouse strain. Importantly, the degradation of
      SIRT1 during MPP+ treatment was mediated by the ubiquitin-proteasome pathway.
      Furthermore, the results indicated that cyclin-dependent kinase 5 (Cdk5) was also
      involved in the decrease of SIRT1 expression, which could be efficiently blocked
      by the inhibition of Cdk5. In conclusion, our findings revealed that the Cdk5
      dependent ubiquitin-proteasome pathway mediated degradation of SIRT1 plays a
      vital role in the progression of PD.

PMID- 29571750
TI  - [Presence of relatives during cardiopulmonary resuscitation: Perspectives of
      health professionals, patients and family in the Basque Country].
AB  - OBJECTIVE: To determine the perception of nurses, doctors, patients and family or
      relatives being present during cardiopulmonary resuscitation (CPR) in adult
      patients. DESIGN: A qualitative exploratory study and thematic analysis were
      developed. SITE: Primary Care, Hospital Care and Emergency Service of the Basque
      Health Service. PARTICIPANTS: The selection of the participants was made through
      intentional sampling. Four focus groups were developed: one of patients and
      family, 2 of nurses, and one of physicians. METHOD: Thematic analysis was
      performed. Triangulation techniques were used between investigators and
      investigator-participant member. The Open code 4.1 statistics software was used.
      RESULTS: Three significant categories were identified: the impact on the family;
      the weight of ethical and legal responsibility; power, place of death, and
      cultural assumptions. CONCLUSIONS: CPR is a social construct influenced by values
      which are situated in specific socio-cultural contexts. In this study, patients
      and family members describe the fear and resistance to being present during CPR.
      Health professionals consider that their decision is complex, and each case must
      be assessed independently, and patients and relatives must be integrated into
      decision-making. Future research should explore in greater depth the subjective
      experience of relatives who have witnessed CPR and the impact of contextual and
      sociocultural elements from the perspectives of relatives.

PMID- 29571751
TI  - Early sustained recovery following first episode psychosis: Evidence from the
      AESOP10 follow-up study.
AB  - OBJECTIVE: To describe the characteristics of individuals with early sustained
      recovery following first episode psychosis. METHODS: Individuals with a first
      episode psychosis were followed-up for ten years. Comparisons were made between
      those with Early Sustained Recovery and those with Other Course types. RESULTS:
      Of 345 individuals, n=43 (12.5%) had Early Sustained Recovery. They were more
      likely than those with Other Course types to be female (OR=2.45; 95% CI: 1.25
      4.81); employed (OR=2.39; 95% CI: 1.22-4.69); in a relationship (OR=2.68; 95% CI:
      1.35-5.32); have a short DUP (OR=2.86; 95% CI: 1.37-5.88); and have a diagnosis
      other than schizophrenia, particularly mania (OR=6.39; 95% CI: 2.52-16.18) or
      brief psychosis (OR=3.64; 95% CI: 1.10-12.10). CONCLUSIONS: Sustained recovery
      from first episode psychosis occurs in a minority.

PMID- 29571752
TI  - The Italian version of the 16-item prodromal questionnaire (iPQ-16): Field-test
      and psychometric features.
AB  - OBJECTIVE: Among current early screeners for psychosis-risk states, the Prodromal
      Questionnaire-16 items (PQ-16) is often used. We aimed to assess validity and
      reliability of the Italian version of the PQ-16 in a young adult help-seeking
      population. METHODS: We included 154 individuals aged 18-35years seeking help at
      the Reggio Emilia outpatient mental health services in a large semirural
      catchment area (550.000 inhabitants). Participants completed the Italian version
      of the PQ-16 (iPQ-16) and were subsequently evaluated with the Comprehensive
      Assessment of At-Risk Mental States (CAARMS). We examined diagnostic accuracy
      (i.e. specificity, sensitivity, negative and positive likelihood ratios, and
      negative and positive predictive values) and content, convergent, and concurrent
      validity between PQ-16 and CAARMS using Cronbach's alpha, Spearman's rho, and
      Cohen's kappa, respectively. We also tested the validity of the adopted PQ-16 cut
      offs through Receiver Operating Characteristic (ROC) curves plotted against
      CAARMS diagnoses and the 1-year predictive validity of the PQ-16. RESULTS: The
      iPQ-16 showed high internal consistency and acceptable diagnostic accuracy and
      concurrent validity. ROC analyses pointed to a cut-off score of >=5 as best cut
      off. After 12months of follow-up, 8.7% of participants with a PQ-16 symptom total
      score of >=5 who were below the CAARMS psychosis threshold at the baseline,
      developed a psychotic disorder. CONCLUSIONS: Psychometric properties of the iPQ
      16 were satisfactory.

PMID- 29571754
TI  - Carotid Intraplaque Hemorrhage in Patients with Embolic Stroke of Undetermined
      Source.
AB  - BACKGROUND: Many embolic strokes are of undetermined source (ESUS). Carotid
      artery intraplaque hemorrhage (IPH), an unstable component of atherosclerosis,
      may be an under-recognized etiology in patients with ESUS. We investigated the
      prevalence of carotid IPH detected noninvasively by magnetic resonance imaging
      (MRI). METHODS: This pilot study analyzed data from a prospective cohort of
      patients with a recent ESUS who underwent MRI for carotid IPH assessment. All
      patients had carotid artery stenosis of less than 50%. The primary outcome was
      the presence of carotid IPH ipsilateral to the cerebral ischemic event. RESULTS:
      The cohort comprised 35 consecutive patients with a recent carotid-territory ESUS
      who underwent carotid MRI (mean age 74.3 +/- 9.6 years). We found ipsilateral and
      contralateral IPH in 7 of 35 patients (20.0%) and in 3 of 35 patients (8.6%),
      respectively (P = .005). CONCLUSIONS: In this sample of patients with ESUS, 1 in
      5 had carotid IPH ipsilateral to their acute infarct, as detected by MRI of the
      vessel wall. Further studies are warranted to investigate carotid IPH as an
      etiology of ESUS.

PMID- 29571755
TI  - Letter to the Editor Regarding "Yield of Computed Tomography (CT) Angiography in
      Patients with Acute Headache, Normal Neurological Examination, and Normal Non
      Contrast CT: A Meta-Analysis".

PMID- 29571753
TI  - Disrupted network cross talk, hippocampal dysfunction and hallucinations in
      schizophrenia.
AB  - Hallucinations characterize schizophrenia, with approximately 59% of patients
      reporting auditory hallucinations and 27% reporting visual hallucinations. Prior
      neuroimaging studies suggest that hallucinations are linked to disrupted
      communication across distributed (sensory, salience-monitoring and subcortical)
      networks. Yet, our understanding of the neurophysiological mechanisms that
      underlie auditory and visual hallucinations in schizophrenia remains limited.
      This study integrates two resting-state functional magnetic resonance imaging
      (fMRI) analysis methods - amplitudes of low-frequency fluctuations (ALFF) and
      functional network connectivity (FNC) - to explore the hypotheses that (1)
      abnormal FNC between salience and sensory (visual/auditory) networks underlies
      hallucinations in schizophrenia, and (2) disrupted hippocampal oscillations (as
      measured by hippocampal ALFF) beget changes in FNC linked to hallucinations. Our
      first hypothesis was supported by the finding that schizophrenia patients
      reporting hallucinations have higher FNC between the salience network and an
      associative auditory network relative to healthy controls. Hippocampal ALFF was
      negatively associated with FNC between primary auditory cortex and the salience
      network in healthy subjects, but was positively associated with FNC between these
      networks in patients reporting hallucinations. These findings provide indirect
      support favoring our second hypothesis. We suggest future studies integrate fMRI
      with electroencephalogram (EEG) and/or magnetoencephalogram (MEG) methods to
      directly probe the temporal relation between altered hippocampal oscillations and
      changes in cross-network functional communication.

PMID- 29571756
TI  - A Validated Swallow Screener for Dysphagia and Aspiration in Patients with
      Stroke.
AB  - BACKGROUND: Early detection of dysphagia is critical to reducing hospital
      complications and length of stay in patients with various types of strokes. The
      aim of this study was to develop and evaluate the DePaul Hospital Swallow
      Screener (DHSS) tool to assess for dysphagia in patients with stroke. METHODS:
      This prospective observational study investigated patients admitted to a
      comprehensive stroke center. The DHSS is composed of a questionnaire containing 8
      nonswallow items and a water swallow test. All patients admitted under a standard
      stroke protocol are screened by the nursing staff using the DHSS and then
      objectively evaluated by a speech-language pathologist using the Mann Assessment
      of Swallowing Ability (MASA). Validity measures and reliability through Cohen's
      kappa-coefficient with associated 95% confidence intervals were calculated.
      RESULTS: A total of 224 patients completed the DHSS and had at least 1 MASA
      score. The overall Content Validity Index score for the DHSS was .92. Compared
      with the MASA dysphagia cutoff value, the DHSS had a specificity of 93% and a
      sensitivity of 69%, and compared with the MASA aspiration risk cutoff value, the
      DHSS had a specificity of 90% and a sensitivity of 70%. Stratified analysis for
      those with any documented stroke (ischemic or hemorrhagic) compared with those
      admitted with transient ischemic attack or no stroke yielded similar sensitivity
      and specificity in both dysphagia and aspiration risk. CONCLUSION: The DHSS is a
      valid and reliable swallow screening tool with moderate agreement, high
      specificity, and reliable predictive values when compared with the MASA.

PMID- 29571757
TI  - Memory Impairment Due to a Small Acute Infarction of the Columns of the Fornix.
AB  - BACKGROUND: Clinically infarction of the columns of the fornix is very rare. It
      is also easy to be overlooked during imaging examination due to the special
      anatomical localization and features of columns of the fornix. In the meantime,
      with memory disorder to be its most prominent manifestation, it is very easily
      false diagnosed as other diseases when the lesion focus is overlooked, causing
      unnecessary invasive examinations like cerebrospinal fluid tests. METHODS: Case
      report and Literature review. RESULTS: We presented a 66-year-old woman with
      memory impairment due to a small acute infarction of the columns of the fornix.
      Through her diagnosis and treatment, we believed that early diagnosis and
      treatment were important to these patients who were enduring the disease. In
      addition, literature review informed us that for those unwilling to undergo
      cerebral angiography or for small cerebrovascular lesions that cannot be detected
      by angiography, 7T magnetic resonance imaging (MRI) might be an ideal diagnostic
      method. CONCLUSION: This case illustrated the significance of MRI in diagnosis
      for patients with acute memory impairment. When reading MRI results, one needs to
      pay attention to identify small lesions at special locations. In addition,
      cerebral apoplexy is still the first consideration of diagnosis when acute memory
      impairment occurs in patients with cerebrovascular disease risk factors.

PMID- 29571758
TI  - S100beta Protein as a Predictor of Poststroke Functional Outcome: A Prospective
      Study.
AB  - BACKGROUND: Stroke is one of the leading causes of disability worldwide. Early
      prediction of poststroke disability using clinical models is of great interest,
      especially in the rehabilitation field. Although some biomarkers and neuroimaging
      techniques have shown potential predictive value, there are still insufficient
      data to support their clinical utility in predicting poststroke functional
      recovery. We aimed to assess the value of serum biomarkers (C-reactive protein
      [CRP], D-dimer, fibrinogen, and S100beta protein) in predicting medium-term (12
      weeks) functional outcome in patients with acute ischemic stroke. METHODS: This
      is an observational, prospective study in a sample of patients hospitalized for
      ischemic stroke (N = 131). Peripheral blood levels of biomarkers of interest were
      determined at admission (CRP, D-dimer, and fibrinogen) or at 48 hours poststroke
      (S100beta protein). Functional status was accessed at 48 hours and 12 weeks
      poststroke using the modified Rankin Scale (mRS). RESULTS: S100beta protein
      levels measured at 48 hours were significantly associated with mRS scores at 12
      weeks (odds ratio = 1.005, 95% confidence interval [CI] [1.005-1.007]; P <.001).
      This association was not seen for the remaining biomarkers of interest. The
      S100beta cutoff for poor functionality at 12 weeks was 140.5 ng/L or more
      (sensibility 83.8%; specificity 71.4%; area under the curve = .80, 95% CI [.722,
      .879]). CONCLUSIONS: S100beta levels in peripheral blood at 48 hours poststroke
      reflect acute stroke severity and predict functional outcome at 12 weeks with a
      cutoff value of 140.5 ng/dL. The value of S100beta as predictor of functional
      recovery after stroke should be emphasized in further clinical research and
      clinical practice.

PMID- 29571759
TI  - A Rare Case of Posterior Circulation Stroke Caused by Bronchial Artery
      Embolization.
AB  - Bronchial artery embolization (BAE) is an effective treatment for massive
      hemoptysis. Stroke is a rare complication of BAE, with only a few cases reported
      in the literature. We report one such case. Posterior circulation strokes after
      BAE can be caused by connections between the vertebral arteries and the bronchial
      arteries (shunting between pulmonary and systemic circulations), backflow of
      embolization material from the bronchial or intercostal arteries to the
      subclavian artery or through backflow of emblospheres into the aortic lumen
      leading to subsequent embolization of the cerebral circulation. New-onset focal
      neurologic signs, change in mental status, or delay in recovery from anesthesia
      after BAE warrants brain imaging to rule out a stroke. Our case had a poor
      outcome, unlike the majority of previously reported cases.

PMID- 29571760
TI  - The "Blush" Sign on Computed Tomography Angiography is an Independent Predictor
      of Hematoma Progression in Primary Hypertensive Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Hypertension is an important etiology of intracerebral
      hemorrhage (ICH) in neurosurgical practice. Contrast extravasation on computed
      tomography angiography, known as the "spot sign", has been described as an
      independent predictor of hematoma progression and clinical deterioration.
      However, its role in hypertensive ICH alone has not been determined and is the
      primary aim of this study. MATERIALS AND METHODS: A retrospective review was
      carried out of patients with hypertensive ICH admitted to our institution between
      May 2014 and December 2016. Evaluation of the neuroimaging studies of these
      patients revealed two distinct morphologies, "spot" and "blush" sign. These
      distinct signs and covariates were tested for association with hematoma expansion
      and mortality using multivariate logistic regression. The accuracy of the "spot"
      and "blush" signs as predictors of hematoma expansion and mortality was
      determined using receiver-operator characteristic (ROC) analysis. RESULTS: A
      total of 54 patients were identified as hypertensive ICH during the study period.
      "spot" sign was observed in 11 (20.4%) of the study population. Contrast
      extravasation (blush-sign) was seen in 7 (14.8%) patients. The "blush" was an
      independent predictor of hematoma expansion (odds ratio [OR] 6.052; confidence
      interval [CI] 1.036-15.945 [P = .012]) and mortality (OR 3.305; CI 1.240-25.414
      [P = .032]). With ROC analysis, the "blush" sign was found to have a better
      predictive value for significant hematoma expansion (area under the curve [AUC]:
      .795) than the spot sign (AUC: .432). CONCLUSION: The "blush" sign has better
      accuracy for predicting hematoma expansion in hypertensive ICH and could be used
      to risk stratify these patients for early therapeutic interventions.

PMID- 29571761
TI  - A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of
      Catheter-Based Cerebral Angiography.
AB  - BACKGROUND: Previous studies have demonstrated the value of cerebral vasodilatory
      capacity assessment for risk stratification in patients with extracranial
      arterial stenosis or occlusion. We describe a new method that assesses cerebral
      vasodilatory capacity as part of catheter-based cerebral angiography. METHODS: We
      assessed regional cerebral blood volume (rCBV) in the arterial distribution of
      interest using a controlled contrast injection through a diagnostic catheter
      placed in the common carotid or the subclavian artery. rCBV maps were created
      using predefined algorithm based on contrast distribution in the venous phase
      (voxel size 0.466 mm3) into high, intermediate, low, and no detectable rCBV
      regions. rCBV maps were acquired again after the administration of intra-arterial
      nicardipine (1.5-2.5 mg), and percentage increases of the area of various grades
      of rCBV were calculated. RESULTS: Three patients with internal carotid artery
      stenosis (32% - 64% in severity) and 1 patient with extracranial vertebral artery
      stenosis (46% in severity) were assessed. There was a variable but consistent
      increase in the area of high rCBV in the ipsilateral hemisphere in 3 patients
      with internal carotid artery flow (5.5%-24.5%) and the cerebellum (9.6%) in 1
      patient with vertebral artery flow assessments. The increase in high rCBV was
      most prominent in the patient who received 2.5 mg (24.5%) and least prominent in
      a patient who received 1.5 mg (5.5%) of intra-arterial nicardipine. There was a
      concurrent reduction in areas of intermediate and low rCBV (shift) in 3 patients,
      and there was an increase in all areas of rCBV grades (addition) in 1 patient.
      CONCLUSIONS: Selective assessment of cerebral vasodilatory response in the
      affected arterial distribution is feasible during catheter-based cerebral
      angiography.

PMID- 29571762
TI  - Bilateral Cerebral Infarctions and Intracardiac Thrombus in a Young Duchenne
      Muscular Dystrophy Patient.
AB  - A 31-year-old man with Duchenne muscular dystrophy was admitted to our center,
      having infarctions in bilateral cerebral hemispheres and an occluded right middle
      cerebral artery. His right middle cerebral artery was spontaneous recanalization
      on the next day, and thrombus in the left ventricle vanished on the eighth day
      after giving warfarin.

PMID- 29571763
TI  - Plaque Characteristics of Patients with Symptomatic Mild Carotid Artery Stenosis.
AB  - BACKGROUND: Carotid revascularization may be considered for severe stenosis, but
      its use for symptomatic mild stenosis (<50%) with vulnerable plaque or ulcer
      remains uncertain. The characteristics of patients with symptomatic mild stenosis
      who underwent revascularization are reviewed. METHODS: The subjects of this study
      were 18 patients with symptomatic mild stenosis (<50%) on angiography from among
      175 patients who underwent revascularization in our department. The plaques were
      evaluated by black-blood magnetic resonance imaging (BB-MRI) and ultrasonography
      (US) and classified into 2 types: type 1 (n = 15), a lesion with an ulcer or
      mobile plaque or thrombosis on angiography or US; and type 2 (n = 3), a lesion
      without any of the above. Fourteen patients underwent carotid endarterectomy
      (CEA), and 4 patients underwent carotid artery stenting. RESULTS: The stenosis on
      angiography was 27.2% +/- 10.7 (5%-41%), and the area carotid artery stenosis
      rate on US was 69.8 +/- 14.5% (44.5%-97%). The stenosis rate of these 2 methods
      was not at all correlated. In type 1 plaque that underwent CEA, 10 of 11 patients
      had vulnerable plaque by histopathology, and 1 patient had thrombus on the plaque
      by operative findings. In type 2 plaque that underwent CEA, all patients had
      vulnerable plaque by histopathology. During the follow-up period, none of the
      patients had restenosis or stroke. CONCLUSIONS: The findings of US and BB-MRI in
      patients with symptomatic mild stenosis (<50%) on angiography are important for
      determining treatment. If BB-MRI or US shows the findings of vulnerable plaque in
      mild stenosis, surgical treatment may be considered for these patients.

PMID- 29571764
TI  - Retinal Microvascular Abnormalities as Surrogate Markers of Cerebrovascular
      Ischemic Disease: A Meta-Analysis.
AB  - BACKGROUND: To determine the predictive value of retinal microvascular
      abnormalities for cerebrovascular ischemic diseases (CVDs), we aimed to
      investigate the quantitative association between retinal microvascular changes
      and CVD subcategories: white matter hyperintensities (WMHIs), lacunar infarcts
      (LIs), and cerebral infarctions (CIs). METHODS: Using Meta-analyses Of
      Observational Studies in Epidemiology guidelines, we searched 6 databases through
      September 2016 for studies evaluating the linkage between retinal microvascular
      abnormalities and WMHI, and LI and CI. Studies were included if they reported
      odds ratios (ORs) and 95% confidence intervals or raw patient level data (that
      were computed into ORs). Unadjusted and vascular risk-factor adjusted ORs were
      pooled into meta-analysis using DerSimonian Laird random effects model. Study
      quality and dissemination biases were assessed and integrated. RESULTS: From
      24,444 search-identified records, 28 prospective studies encompassing 56,379
      patients were eligible for the meta-analysis. After vascular risk-factor
      adjustment, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01
      1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular
      dilation was associated with LI (OR, 1.46 [1.10-1.93]), and retinal hemorrhages
      with WMHI (OR, 2.23 [1.34-3.70]). Any retinopathy exhibited significant
      association with CI (OR, 1.96 [1.65-2.50]). Heterogeneity was significant
      (I2>50%) for all syntheses except retinal hemorrhages and WMHI, and retinopathy
      and CI (I2=0 ? 0%). Associations remained significant after adjustments for
      quality and publication bias. CONCLUSIONS: We found the most significant
      association between retinal hemorrhages and WMHI. Focal arteriolar narrowing and
      retinopathy predicted CVD subtypes after risk-factor adjustment, suggesting that
      features different than traditional vascular risk factors, are involved in CVD
      pathophysiology.

PMID- 29571765
TI  - Paradoxical Brain Embolism in Elderly Subjects with Small Atrial Septal Defects.
AB  - BACKGROUND: Atrial septal defects have a low prevalence in the general
      population, and are recognized as a rare cause of paradoxical brain embolism.
      METHODS: We extensively examined stroke causes in patients with acute stroke
      admitted to a single stroke center within 1 year. RESULTS: Among 186 consecutive
      patients, transesophageal or transthoracic echocardiography revealed 5 cases of
      paradoxical brain embolism: 3 (1.6%) were related to atrial septal defects,
      whereas 2 were patent foramen ovale patients. Although right-to-left shunt may
      have occurred after the development of acute pulmonary embolism in atrial septal
      defects case #1, the Valsalva maneuver elicited right-to-left shunt in atrial
      septal defects cases #2 and #3. The 3 cases were elderly (>60 years old),
      harbored small defects with normal systemic hemodynamics, and had not experienced
      any clinical symptoms related to atrial septal defects. CONCLUSIONS: Small atrial
      septal defect may cause paradoxical embolism as its initial related event,
      particularly in elderly subjects.

PMID- 29571766
TI  - Dehydroepiandrosterone reduces accumulation of lipid droplets in primary chicken
      hepatocytes by biotransformation mediated via the cAMP/PKA-ERK1/2 signaling
      pathway.
AB  - Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to
      control fat deposition, but the mechanism of this action is poorly understood. In
      this study, we demonstrated that DHEA increased phosphorylation of AMP-activated
      protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of
      sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid
      synthase and enhanced expression of peroxisome proliferators-activated receptor
      alpha and carnitine palmitoyl transferase-I, ultimately leading to the reduction
      of lipid droplet accumulation in primary chicken hepatocytes. We found that DHEA
      activates the cyclic adenosine 3', 5'-monophosphate/protein kinase A -
      extracellular signal-regulated kinase 1/2 (cAMP/PKA-ERK1/2) signaling pathway,
      which regulates the conversion of DHEA into testosterone and estradiol by
      increasing the 17beta-hydroxysteroid dehydrogenase and aromatase protein
      expression. Importantly, the fat-reducing effects of DHEA are more closely
      associated with the conversion of DHEA into estradiol than with the action of
      DHEA itself as an active biomolecule, or to its alternative metabolite,
      testosterone. Taken together, our results indicate that DHEA is converted into
      active hormones through activation of the cAMP/PKA-ERK1/2 signaling pathway; the
      fat-reducing effects of DHEA are achieved through its conversion into estradiol,
      not testosterone, and not through direct action of DHEA itself, which led to the
      activation of the p-AMPK in primary chicken hepatocytes. These data provide novel
      insight into the mechanisms underlying the action of DHEA in preventing fat
      deposition, and suggest potential applications for DHEA treatment to control fat
      deposition or as an agent to treat disorders related to lipid metabolism in
      animals and humans.

PMID- 29571767
TI  - Phospholipase D1 downregulation by alpha-synuclein: Implications for
      neurodegeneration in Parkinson's disease.
AB  - We have previously shown that phospholipase D (PLD) pathways have a role in
      neuronal degeneration; in particular, we found that PLD activation is associated
      with synaptic injury induced by oxidative stress. In the present study, we
      investigated the effect of alpha-synuclein (alpha-syn) overexpression on PLD
      signaling. Wild Type (WT) alpha-syn was found to trigger the inhibition of PLD1
      expression as well as a decrease in ERK1/2 phosphorylation and expression levels.
      Moreover, ERK1/2 subcellular localization was shown to be modulated by WT alpha
      syn in a PLD1-dependent manner. Indeed, PLD1 inhibition was found to alter the
      neurofilament network and F-actin distribution regardless of the presence of WT
      alpha-syn. In line with this, neuroblastoma cells expressing WT alpha-syn
      exhibited a degenerative-like phenotype characterized by a marked reduction in
      neurofilament light subunit (NFL) expression and the rearrangement of the F-actin
      organization, compared with either the untransfected or the empty vector
      transfected cells. The gain of function of PLD1 through the overexpression of its
      active form had the effect of restoring NFL expression in WT alpha-syn neurons.
      Taken together, our findings reveal an unforeseen role for alpha-syn in PLD
      regulation: PLD1 downregulation may constitute an early mechanism in the initial
      stages of WT alpha-syn-triggered neurodegeneration.

PMID- 29571768
TI  - Immune-related gene expression and physiological responses in rainbow trout
      (Oncorhynchus mykiss) after intraperitoneal administration of Rhodomyrtus
      tomentosa leaf extract: A potent phytoimmunostimulant.
AB  - The immunostimulatory effects of Rhodomyrtus tomentosa leaf extract were
      evaluated in rainbow trout through changes in expression profile of genes
      involved in innate immune and antioxidant response, hematology and stress
      indicators. The concentrations of R. tomentosa at 10 and 100 MUg per fish were
      administrated by intraperitoneal injection, alone or in combination with LPS.
      After 6 h of administration, the gene expression was measured in head kidney,
      spleen, and intestine. Results indicated that R. tomentosa exerted
      immunostimulatory effects by inducing the expression of il10, saa, hepcidin, and
      sod in head kidney and the expression of il10, tgfbeta, and inos in intestine. In
      combination with LPS, the plant suppressed the expression of pro-inflammtory
      cytokine il1beta, il8 and other consisting of saa and gpx1 in head kidney and
      il1beta in spleen, pointing out its anti-inflammatory activities. Furthermore,
      the plant did not exert any impact on hematological parameters, but it was able
      to reduce cortisol levels when co-administered with LPS, indicating that R.
      tomentosa could attenuate stress response in rainbow trout. Our observations
      suggest that R. tomentosa induced the expression of genes involved in cytokine
      and innate immune response and modulated the physiological stress response as
      indicated by the suppressed cortisol in rainbow trout.

PMID- 29571769
TI  - Serum biochemistry, histology and transcriptomic profile analysis reflect liver
      inflammation and damage following dietary histamine supplementation in yellow
      catfish (Pelteobagrus fulvidraco).
AB  - Previous studies suggested that diets containing high levels of histamine
      influenced digestive system of aquatic animals. In addition, the exogenous
      histamine was first detoxified by diamine oxidase in the intestine, while the
      rest of histamine was further detoxified in the liver. Thus, based on the
      evidence from the previous studies, we hypothesized that high levels of histamine
      may lead to damage on liver of the aquatic animals. Here, in current attempt, we
      sought to investigate the toxic effect of histamine on yellow catfish
      (Pelteobagrus fulvidraco) liver physiology and pathogenesis. In the present
      study, yellow catfish were fed for 56 days on diets supplemented with 1000 mg kg
      1 histamine (His) or a basal diet as the control group (Con). A significant
      change on the morphology of the intestine and liver was observed, followed with
      an induction of serum activity of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT). Furthermore, the transcriptomic analysis was performed to
      gain an overview of the gene expression profile in liver between control and
      histamine supplemented groups. Through the bioinformatics analysis, 431
      differentially expressed genes were identified. Among these genes, Gene Ontology
      enrichment analysis (GO) suggests that immune-related genes are significantly
      dysregulated. In addition, TNF signaling pathway is enriched in Kyoto
      Encyclopedia of Genes and Genomes analysis (KEGG), and is also the dominant
      pathway in immune system, suggesting that the inflammatory response and apoptosis
      of hepatocytes are induced by exogenous histamine.

PMID- 29571770
TI  - Commentary to: Cause of Cambrian explosion - Terrestrial or cosmic? Steele, E.J.
      et al.

PMID- 29571771
TI  - Unde venis? Geographic profiling for the prevention of gastric cancer.

PMID- 29571772
TI  - Self-expandable metal stents in malignant biliary obstruction: Back to the roots
      with uncovered stents as the "new" standard?

PMID- 29571773
TI  - Endoscopic submucosal dissection for nonpolypoid colorectal dysplasia in patients
      with inflammatory bowel disease: in medias res.

PMID- 29571774
TI  - Colorectal polyp snaring: the smaller, the colder, the bigger!

PMID- 29571775
TI  - Endoscopic submucosal dissection learning curve and role in the treatment of
      Barrett's neoplasia.

PMID- 29571776
TI  - Response.

PMID- 29571777
TI  - Fine-needle biopsy sampling under EUS guidance: Is one needle tip really better
      than the other?

PMID- 29571778
TI  - Retraction notice to "Long-term outcomes of per-oral endoscopic myotomy in
      patients with achalasia with a minimum follow-up of 2 years: an international
      multicenter study": [YMGE 85 (2017) 927-933].
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This
      article has been retracted due to overlapping/duplicate material. Data from some
      patients from this study have previously been published in other journals without
      cross-referencing. Twenty patients overlap with a paper by Kumbhari et al.1
      Thirty-five patients overlap with the study by Ngamruengphong et al.2.

PMID- 29571779
TI  - The ASGE'S vision for developing clinical practice guidelines: the path forward.

PMID- 29571780
TI  - How do we assess what lies beneath in eosinophilic esophagitis?

PMID- 29571781
TI  - Influence of image reconstruction parameters on cardiovascular risk
      reclassification by Computed Tomography Coronary Artery Calcium Score.
AB  - OBJECTIVE: To investigate the influence of different CT reconstruction parameters
      on coronary artery calcium scoring (CACS) values and reclassification of
      predicted cardiovascular (CV) risk. METHODS: CACS was evaluated in 113 patients
      undergoing ECG-gated 64-slice CT. Reference CACS protocol included standard
      kernel filter (B35f) with slice thickness/increment of 3/1.5 mm, and field-of
      view (FOV) of 150-180 mm. Influence of different image reconstruction algorithms
      (reconstructed slice thickness/increment 2.0/1.0-1.5/0.8-3.0/2.0-3.0/3.0 mm;
      slice kernel B30f-B45f; FOV 200-250 mm) on Agatston score was assessed by Bland
      Altman plots and concordance correlation coefficient (CCC) analysis.
      Classification of CV risk was based on the Mayo Clinic classification. RESULTS:
      Different CACS reconstruction parameters showed overall good accuracy and
      precision when compared with reference protocol. Protocols with larger FOV,
      thinner slices and sharper kernels were associated with significant CV risk
      reclassification. Use of kernel B45f showed a moderate positive correlation with
      reference CACS protocol (Agatston CCC = 0.67), and yielded significantly higher
      CACS values (p < .05). Reconstruction parameters using B30f or B45f kernels, 250
      mm FOV, or slice thickness/increment of 2.0/1.0 mm or 1.5/0.8 mm, were associated
      with significant reclassification of CV risk (p < .05). CONCLUSIONS: Kernel, FOV,
      slice thickness and increment are major determinants of accuracy and precision of
      CACS measurement. Despite high agreement and overall good correlation of
      different reconstruction protocols, thinner slices thickness and increment, and
      sharper kernels were associated with significant upward reclassification of CV
      risk. Larger FOV determined both upward and downward reclassification of CV risk.

PMID- 29571782
TI  - Attenuation values of renal parenchyma in virtual noncontrast images acquired
      from multiphase renal dual-energy CT: Comparison with standard noncontrast CT.
AB  - OBJECTIVES: To compare the renal parenchyma attenuation of virtual noncontrast
      (VNC) images derived from multiphase renal dual-energy computed tomography (DECT)
      with standard noncontrast (SNC) images, and to determine the optimum phase for
      VNC images. MATERIALS AND METHODS: Twenty-nine men and 16 women (mean age, 61 +/-
      13 years; range, 37-89 years) underwent dynamic renal DECT (100/Sn140 kVp) were
      included in this institutional review board-approved retrospective study. There
      were four phases of the scan, which included noncontrast, corticomedullary (CMP),
      nephrographic (NP), and excretory phases (EP). The VNC images was generated from
      CMP, NP and EP. CT numbers of SNC images and VNC images of each phases were
      measured in the renal cortex and medulla. Mean standard deviation of subcutaneous
      fat was measured as image noise on SNC and VNC images. Radiation dose was
      recorded and potential radiation dose reduction was estimated. Results were
      tested for statistical significance using the unpaired t-test and agreement using
      Bland-Altman plot analysis. RESULTS: The difference in mean attenuation between
      SNC and each phase of VNC images were <=4 HU. The mean attenuation of renal
      cortex and medulla was 33.2 +/- 4.4 HU, and 34.2 +/- 4.8 HU in SNC, 33.6 +/- 7.6
      HU and 31.1 +/- 8.3 HU in VNC of CMP, 34.8 +/- 8.6 HU and 35.6 +/- 8.5 HU in VNC
      of NP, 31.5 +/- 7.6 HU and 32.4 +/- 7.5 HU in VNC of EP. In VNC of CMP, the
      attenuation of the cortex was higher than the medulla (p < 0.05), and the
      attenuation of medulla was significant lower than that of SNC (p < 0.01). In VNC
      of NP, the attenuation of renal cortex was higher than SNC (p < 0.05). In VNC of
      EP, the attenuation of cortex and medulla were lower than SNC (p < 0.05), and
      inadequate iodine subtraction in collecting system was noted. Image noise was
      significantly greater in SNC (p < 0.001). Mean radiation dose reduction
      achievable by removing the SNC was 12.3% +/- 0.9%. CONCLUSIONS: VNC images from
      multiphase renal DECT were similar to SNC images. Using the nephrographic phase
      can gives more comparable VNC images to SNC images in renal parenchyma than other
      phases.

PMID- 29571783
TI  - Beam-hardening in 70-kV Coronary CT angiography: Artifact reduction using an
      advanced post-processing algorithm.
AB  - PURPOSE: To investigate the effect of an iterative beam-hardening correction
      algorithm (iBHC) on artifact reduction and image quality in coronary CT
      angiography (cCTA) with low tube voltage. MATERIAL AND METHODS: Thirty-six
      patients (17 male, mean age, 57.3 +/- 14.5 years) were prospectively enrolled in
      this IRB-approved study and underwent 70-kV cCTA using a third-generation dual
      source CT scanner. Images were reconstructed using a standard algorithm (Bv36)
      both with and without the iBHC technique. Several region-of-interest (ROI)
      measurements were performed in the inferior wall of the left ventricle (LV), an
      area prone to beam-hardening, as well as other myocardial regions. Coronary
      contrast-to-noise (CNR) and signal-to-noise ratios (SNR) were calculated. Two
      radiologists assessed subjective image quality. RESULTS: The iBHC algorithm
      generally increased myocardial attenuation in all ROIs (P < 0.566); however, the
      increase was significantly more distinct in beam-hardening prone areas such as
      the inferior LV (increase, +13.9 HU, +18.6%, P < 0.001), compared to the
      remaining myocardium (increase, +4.4 HU, +4.5%, P < 0.003). While no significant
      difference was found for image noise (P < 0.092), greater CNR and SNR values for
      the left main coronary artery (increase, +20.7% and +17.3%, respectively) were
      found using the iBHC algorithm (both with P < 0.001). Subjective image quality
      was comparable between both image series (P = 0.217). CONCLUSION: The iBHC post
      processing algorithm leads to significantly reduced beam-hardening while
      providing improved objective and equivalent subjective image quality in 70-kV
      cCTA.

PMID- 29571784
TI  - Predictive factors for treatment response using dual-energy computed tomography
      in patients with advanced lung adenocarcinoma.
AB  - PURPOSE: This study aimed to investigate whether the quantitative parameters of
      dual-energy computed tomography (DECT) can predict the effects of chemotherapy in
      advanced adenocarcinoma based on the Response Evaluation Criteria in Solid Tumors
      (RECIST) guidelines. MATERIALS AND METHODS: A total of 90 patients (59 males, 31
      females, age 61.4 +/- 12.3 (23-85)) with unresectable lung adenocarcinoma (TNM
      stage IIIB or IV) who underwent DECT before chemotherapy were prospectively
      included in this study. By comparing baseline studies with the best response
      achieved during 1 st line chemotherapy, patients were divided into two groups
      according to RECIST (version 1.1) guidelines as follows; responders (CR or PR)
      and non-responders (SD or PD). Quantitative measurements were performed on
      baseline DECT, and a logistic regression model was used to evaluate predictive
      factors for a response to chemotherapy. RESULTS: Among 90 patients, 38 were
      categorized as responders, while 52 patients were non-responders. The mean iodine
      concentration measurements were significantly higher in responders compared with
      non-responders (1.81 +/- 0.51 vs 1.33 +/- 0.76 mg/ml, p < 0.001). On multivariate
      analysis, EGFR mutation (odds ratio (OR): 3.116, 95% confidential interval
      (CI):1.182-8.213, p = .019) and iodine concentration (OR: 1.112, 95% CI:1.034
      1.196, p = .006) were found to be significant for predicting a treatment
      response. CONCLUSIONS: Dual-energy CT using a quantitative analytic method based
      on iodine concentration measurements can be used to predict the effects of
      chemotherapy in patients with advanced adenocarcinoma.

PMID- 29571785
TI  - Low-dose chest computed tomography screening of subjects exposed to asbestos.
AB  - OBJECTIVES: The primary aim was to reveal the prevalence of lung cancer (LC) and
      malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure
      (AE). We also examined pulmonary or pleural changes correlated with the
      development of LC. MATERIALS AND METHODS: This was a prospective, multicenter,
      cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012.
      They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8%
      former or current smokers; and 21.2% never smokers. We screened subjects using
      low-dose computed tomography (CT). The CT images were taken with a CT dose Index
      of 2.7 mGy. The evaluated CT findings included subpleural curvilinear
      shadow/subpleural dots, ground glass opacity or interlobular reticular opacity,
      traction bronchiectasia, honeycombing change, parenchymal band, emphysema
      changes, pleural effusion, diffuse pleural thickening, rounded atelectasis,
      pleural plaques (PQs), and tumor formation. RESULTS: The PQs were detected in
      most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic
      changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was
      confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The
      prevalence of LC was 2.5% in patients with a smoking history, which was
      significantly higher than that in never smokers (0.7%, p = 0.027). The prevalence
      of LC was 2.8% in subjects with emphysema changes, which was higher than that of
      subjects without those findings (1.6%); although, the difference was not
      statistically significant (p = 0.056). The prevalence of LC in subjects with both
      fibrotic plus emphysema changes was 4.0%, which was significantly higher than
      that of subjects with neither of those findings (1.8%, p = 0.011). Logistic
      regression analysis revealed smoking history, fibrotic plus emphysema changes,
      and pleural effusion as significant explanatory variables. CONCLUSIONS: Smoking
      history, fibrotic plus emphysema changes, and pleural effusion were correlated
      with the prevalence of LC.

PMID- 29571786
TI  - Dynamic contrast enhanced magnetic resonance lymphangiography: Categorization of
      imaging findings and correlation with patient management.
AB  - OBJECTIVE: To review the technical aspects and categorize the imaging findings of
      dynamic contrast enhanced magnetic resonance lymphangiography (DCMRL) and
      correlate the findings with patient management options. MATERIALS AND METHODS: A
      retrospective review of patients who underwent DCMRL between June 2012 and August
      2017 at a tertiary care paediatric hospital was performed. Twenty-five DCMRL
      studies were performed in 23 patients (9 males, 13 females, 1 ambiguous gender)
      with a median age of 4 years (range: 1 month-29 years). DCMRL imaging findings
      were reviewed, categorized and the impact on patient management was studied.
      RESULTS: DCMRL was technically successful in 23/25 (92%) studies. DCMRL findings
      were categorized based on the status of central conducting lymphatics (CCL) and
      alternate lymphatic pathways as follows: Type 1 - normal CCL with no alternate
      lymphatic pathways, Type 2 - partial (2a) or complete (2b) non-visualization of
      CCL with reflux of contrast into alternate pathways and Type 3 - normal CCL with
      additional filling of alternate pathways. Type 1 DCMRL patients (n = 5) were
      reassured and conservative management was continued, Type 2 patients (n = 10) had
      evidence of CCL obstruction hence thoracic duct ligation or embolization was
      avoided and other options such as lymphatic fluid diversion using Denver(r) shunt
      or lympho-venous anastomosis were used, and Type 3 patients (n = 8) were
      evaluated for elevated central venous pressure as a cause of lymphatic backflow
      in addition to Denver(r) shunt, lympho-venous anastomosis, thoracic duct ligation
      or embolization. CONCLUSION: DCMRL is an evolving imaging technique for
      understanding abnormalities of the central conducting lymphatics. Categorization
      of imaging findings may be helpful in guiding selection of management options.

PMID- 29571787
TI  - Advantages of high b-value diffusion-weighted imaging for preoperative
      differential diagnosis between embryonal and ependymal tumors at 3 T MRI.
AB  - PURPOSE: It is often difficult to distinguish between embryonal and ependymal
      tumors using conventional MR imaging. The apparent diffusion coefficient (ADC)
      calculated from diffusion-weighted images (DWI) has been widely used for
      diagnosis, but its usefulness for differential diagnosis between embryonal and
      ependymal tumors has not been determined yet. Both DWI properties and ADC values
      of these two types of tumor at regular and high b-values on a 3 T MR scanner were
      retrospectively reviewed. MATERIALS AND METHODS: DWI at 3 T was acquired for 16
      patients with embryonal tumors (including medulloblastoma, CNS embryonal tumors
      (NOS), and atypical teratoid/rhabdoid tumor), and 7 patients with ependymal
      tumors (including ependymoma and anaplastic ependymoma). ADC was measured by
      manually placing multiple regions of interest (ROIs) on ADC maps corresponding to
      enhancing lesions on contrast-enhanced T1-weighted images, both on standard (b
      1000) and high (b-4000) b-value DWI. The minimum ADC (ADC-MIN) was calculated
      from several ROIs placed on each tumor. The relationship between tumor cell
      density and ADC-MIN was also investigated. RESULTS: Both at b-1000 and b-4000,
      ADC-MIN was significantly lower in embryonal tumors than in ependymal tumors.
      Embryonal tumors could be completely discriminated from ependymal tumors using
      both b-values, but ADC-MIN at b-4000 (t-value = -8.312, p < 0.001) was better
      than ADC-MIN at b-1000. There was a stronger negative correlation between cell
      density and ADC-MIN at b-4000 (r2 = 0.50, p < 0.001) than with ADC-MIN at b-1000
      (r2 = 0.41, p < 0.001). CONCLUSION: Evaluating ADC-MIN at b-4000 would be a
      useful tool for distinguishing embryonal from ependymal tumors.

PMID- 29571788
TI  - Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso
      lateral prefrontal cortex.
AB  - The repetitive application of transcranial magnetic stimulation (rTMS) on left
      dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be
      beneficial for treating various neuropsychiatric or neuropsychological disorders,
      but its neural mechanisms still remain unclear. The purpose of this study was to
      measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow
      (CBF) collected from 40 young healthy subjects before and after applying 20 Hz
      left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and
      after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that
      20 Hz DLPFC rTMS induced CBF redistribution in the default mode network,
      including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but
      reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn't
      produce any rCBF changes. After controlling SHAM effects, only the rCBF increase
      in MTC/hippocampus remained. Those data suggest that the beneficial effects of
      high-frequency rTMS may be through a within-network rCBF redistribution.

PMID- 29571789
TI  - Virtual single source CT using dual source acquisition: Clinical applicability in
      run-off CT-angiography for intra-individual comparison of different scan
      protocols.
AB  - PURPOSE: Virtual single source computed tomography (VSS-CT) acquisition on a dual
      source CT (DSCT) has been demonstrated to allow for dose-neutral intra-individual
      comparison of three acquisition protocols at different radiation dose levels
      (RDL) within one acquisition in a phantom. The purpose of this study was twofold:
      first to evaluate the applicability of VSS-CT in patients and second to optimize
      the task-dependent trade-off between radiation dose and image quality of lower
      extremity CT angiography (run-off CTA). MATERIAL AND METHODS: In this IRB
      approved prospective study 52 patients underwent run-off CTA between 06/2012 and
      06/2013. VSS-CT acquisition was conducted using a first generation DSCT applying
      equal X-ray tube settings (120 kVp), collimation (2 * 32 * 0.6 mm), and slice
      thickness (1.0 mm) but different effective tube current-time products (tube A: 80
      mAs, tube B: 40 mAs). Three different image datasets representing three different
      radiation dose levels (RDL40, RDL80, RDL120) were reconstructed using a soft
      kernel from the raw data of tube B, tube A or both tubes combined. Dose length
      products (DLP) of each raw data set were documented. Quantitative image quality
      (IQ) was assessed for five anatomical levels using image noise and contrast-to
      noise ratio (CNR). To investigate dose efficiency of each acquisition, the dose
      weighted CNR (CNRD) was determined. Qualitative IQ was evaluated by two blinded
      readers in consensus using a 5-point Likert scale and compared with a Friedman-
      and posthoc Wilcoxon test. RESULTS: Mean DLP was 200 +/- 40, 400 +/- 90 and 600
      +/- 130 mGy.cm for the RDL40, RDL80 and RDL120, respectively. Image noise and CNR
      were best for RDL120 and decreased significantly for RDL80 and RDL40, independent
      of the anatomic level (p < 0.001). CNRD showed no significant differences at the
      abdominal and pelvic level between the investigated radiation dose levels.
      However, for thigh to foot level a significant increase of CNRD was noted between
      RDL120, RDL80 and RDL40. Significant differences of qualitative IQ were observed
      between RDL120 and RDL40 from the abdominal to the foot level, whereas no
      difference was seen for the other dose levels. CONCLUSION: Radiation dose
      splitting with VSS-CT can be applied to run-off CTA facilitating intra-individual
      comparison of different acquisition protocols without additional radiation
      exposure. Furthermore, a radiation dose reduction potential for run-off CTA of
      approximately 1/3 as compared to the acquisition protocol recommended by the
      manufacturer could be identified in this study.

PMID- 29571790
TI  - Breast strain elastography: Observer variability in data acquisition and
      interpretation.
AB  - OBJECTIVE: To analyze the observer reproducibility of breast strain elastography
      in elasticity image acquisition and elasticity image interpretation. METHODS:
      This was an institutional ethics committee approved prospective study. One
      hundred twenty-four breast lesions in 118 women (mean age 45.39 +/- 12.97 years
      old, range 21-77 years old) were examined with strain elastography by two blinded
      radiologists in turn. Three blinded observers separately reviewed and recorded
      the elasticity score of each lesion obtained by the two performers. The
      interobserver reproducibility of elasticity image acquisition between the two
      performers, the interobserver and intraobserver reproducibility of elasticity
      image interpretation among observers were evaluated. The diagnostic performance
      of strain elastography was compared between the two performers. RESULTS: Fifty
      three lesions were malignant and 71 were benign. The interobserver kappa value
      was 0.438 for the elasticity score between the two performers. Between the three
      observers, the overall interobserver and intraobserver kappa value was 0.365 and
      0.655, respectively. There was no significant difference of the area under the
      receiver operator characteristic curve (Az) value for the elasticity score
      between performer 1 and 2 (P = 0.143). CONCLUSIONS: Our results suggested
      moderate interobserver reproducibility in breast strain elasticity image
      acquisition, poor interobserver and good intraobserver agreement in image
      interpretation.

PMID- 29571791
TI  - Utility of MRI with morphologic and diffusion weighted imaging in the detection
      of post-treatment nodal disease in head and neck squamous cell carcinoma.
AB  - PURPOSE: To determine the diagnostic performance of morphologic MRI with
      diffusion weighted imaging (DWIMRI) for the detection of post-treatment lymph
      node (LN) recurrence of head and neck squamous cell carcinoma (HNSCC). METHODS:
      This retrospective study is based on 33 HNSCC patients who underwent DWIMRI with
      apparent diffusion coefficient (ADC) measurements for suspected post-treatment
      loco-regional failure. Two radiologists, blinded to clinical/histopathological
      data, analyzed MR images according to established morphologic criteria and
      measured ADC values by drawing regions of interest on each normal/abnormal
      looking lymph node (LN). Histopathological findings in 40 neck dissections, 133
      LN-levels and 755 LNs served as gold standard. RESULTS: Malignant LNs had lower
      ADCmean values than benign LNs (1.15 +/- 0.35 * 10-3 mm2/s versus 1.28 +/- 0.28 *
      10-3 mm2/s, p = .028). The optimal ADCmean threshold to differentiate malignant
      from benign LNs was 1.1695 * 10-3 mm2/s. Sensitivity, specificity, positive (PPV)
      and negative (NPV) predictive values (95%CI in parentheses) of DWIMRI with
      morphologic criteria and ADCmean <1.1695 * 10-3 mm2/s were: (a) 100%(86.2;100),
      44.4%(15.3;77.3), 86.1%(69.7;94.7), and 100%(39.5;100) per neck dissection; (b)
      83.6%(69.7;92.2), 91.6%(83.0;96.2), 85.4%(71.6;93.4), and 90.5%(81.7;95.5) per LN
      level; (c) 53.1%(43.5;62.4), 95.5%(93.5;96.9), 67.4%(56.6;76.7), and
      92.0%(89.6;93.9) per LN, respectively. CONCLUSION: The high NPV of DWIMRI
      irrespective of analysis type (per neck dissection/per neck level/per lymph node)
      make it a useful follow-up tool after treatment.

PMID- 29571792
TI  - Diagnostic accuracy of biparametric vs multiparametric MRI in clinically
      significant prostate cancer: Comparison between readers with different
      experience.
AB  - BACKGROUND: MRI plays a crucial role to identify men with a high likelihood of
      clinically significant prostate cancer who require immediate biopsy. The added
      value of DCE MRI in combination with T2-weighted imaging and DWI is controversial
      (risks related to gadolinium administration, duration of MR exam, financial
      burden, effects on diagnostic performance). A comparison of a biparametric and a
      standard multiparametric MR imaging protocol, taking into account the different
      experience of the readers, may help to choose the best MR approach regarding
      diagnostic performance. PURPOSE: To determine the added value of dynamic
      contrasted-enhanced imaging (DCE) over T2-weighted imaging (T2-WI) and diffusion
      weighted imaging (DWI) for the detection of clinically significant prostate
      cancer, and to evaluate how it affects the diagnostic performance of three
      readers with different grade of experience in prostate imaging. MATERIALS AND
      METHODS: Eighty-five patients underwent prostate MR examination at 1.5 T MR
      scanner performed because of elevated prostate-specific antigen level and/or
      suspicion of prostate cancer at digital rectal examination. Two MR images sets
      (Set 1 = biparametric, Set 2 = multiparametric) were retrospectively and
      independently scored by three radiologists with 7, 3 and 1 years of experience in
      prostate MR imaging respectively, according to PI-RADS v2. Sensitivity,
      specificity, positive predictive value, and negative predictive value were
      calculated by dichotomizing reader scores. Receiver operating characteristic
      (ROC) analysis was performed and areas under the curve (AUCs) were calculated for
      each reader and image set. A comparison of ROC curves was performed to test the
      difference between the areas under the ROC curves among the three readers.
      RESULTS: There was no significant difference regarding the detection of
      clinically significant tumor among the three readers between the two image sets.
      The AUC for the bi-parametric and multi-parametric MR imaging protocol was
      respectively 0.68-0.72 (Reader 1), 0.72-0.70 (Reader 2) and 0.60-0.54 (Reader 3).
      ROC curve comparison revealed no statistically significant differences for each
      protocol among the most experienced (Reader 1) and the other readers (Readers 2
      3). CONCLUSION: The diagnostic accuracy of a bi-parametric MR imaging protocol
      consisting of T2-weighted imaging and DWI is comparable with that of a standard
      multi-parametric imaging protocol for the detection of clinically significant
      prostate cancer. The experience of the reader does not significantly modify the
      diagnostic performance of both MR protocols.

PMID- 29571793
TI  - Predictive quantitative sonographic features on classification of hot and cold
      thyroid nodules.
AB  - PURPOSE: This study investigated the potentiality of ultrasound imaging to
      classify hot and cold thyroid nodules on the basis of textural and morphological
      analysis. METHODS: In this research, 42 hypo (hot) and 42 hyper-function (cold)
      thyroid nodules were evaluated through the proposed method of computer aided
      diagnosis (CAD) system. To discover the difference between hot and cold nodules,
      49 sonographic features (9 morphological, 40 textural) were extracted. A support
      vector machine classifier was utilized for the classification of LNs based on
      their extracted features. RESULTS: In the training set data, a combination of
      morphological and textural features represented the best performance with area
      under the receiver operating characteristic curve (AUC) of 0.992. Upon testing
      the data set, the proposed model could classify the hot and cold thyroid nodules
      with an AUC of 0.948. CONCLUSIONS: CAD method based on textural and morphological
      features is capable of distinguishing between hot from cold nodules via 2
      Dimensional sonography. Therefore, it can be used as a supplementary technique in
      daily clinical practices to improve the radiologists' understanding of
      conventional ultrasound imaging for nodules characterization.

PMID- 29571794
TI  - Non-contrast enhanced magnetic resonance imaging detects mosaic signal intensity
      in early cystic fibrosis lung disease.
AB  - OBJECTIVES: To determine if morphological non-contrast enhanced magnetic
      resonance imaging (MRI) of the lung is sensitive to detect mosaic signal
      intensity in infants and preschool children with cystic fibrosis (CF). MATERIALS
      AND METHODS: 50 infant and preschool CF patients (mean age 3.5 +/- 1.4y, range 0
      6y) routinely underwent morphological (T2-weighted turbo-spin echo sequence with
      half-Fourier acquisition, HASTE) and contrast-enhanced 4D perfusion MRI (gradient
      echo sequence with parallel imaging and echo sharing, TWIST). MRI studies were
      independently scored by two readers blinded for patient age and clinical data
      (experienced Reader 1 = R1, inexperienced Reader 2 = R2). The extent of lung
      parenchyma signal abnormalities on HASTE was rated for each lobe from 0 (normal),
      1 (<50% of lobe affected) to 2 (>=50% of lobe affected). Perfusion MRI was rated
      according to the previously established MRI score, and served as the standard of
      reference. RESULTS: Inter-method agreement between MRI mosaic score and perfusion
      score was moderate with kappa = 0.58 (confidence interval 0.45-0.71) for R1, and
      with kappa = 0.59 (0.46-0.72) for R2. Bland-Altman analysis revealed a slight
      tendency of the mosaic score to underestimate perfusion abnormalities with a
      score bias of 0.48 for R1 and 0.46 for R2. Inter-reader agreement for mosaic
      score was substantial with kappa = 0.71 (0.62-0.79), and a low bias of 0.02.
      CONCLUSIONS: This study demonstrates that non-contrast enhanced MRI reliably
      detects mosaic signal intensity in infants and preschool children with CF,
      reflecting pulmonary blood volume distribution. It may thus be used as a
      surrogate for perfusion MRI if contrast material is contra-indicated or
      alternative techniques are not available.

PMID- 29571795
TI  - Texture analysis of apparent diffusion coefficient maps for treatment response
      assessment in prostate cancer bone metastases-A pilot study.
AB  - OBJECTIVE: To evaluate whole-lesion volumetric texture analysis of apparent
      diffusion coefficient (ADC) maps for assessing treatment response in prostate
      cancer bone metastases. MATERIALS AND METHODS: Texture analysis is performed in
      12 treatment-naive patients with 34 metastases before treatment and at one, two,
      and three months after the initiation of androgen deprivation therapy. Four first
      order and 19 second-order statistical texture features are computed on the ADC
      maps in each lesion at every time point. Repeatability, inter-patient
      variability, and changes in the feature values under therapy are investigated.
      Spearman rank's correlation coefficients are calculated across time to
      demonstrate the relationship between the texture features and the serum prostate
      specific antigen (PSA) levels. RESULTS: With few exceptions, the texture features
      exhibited moderate to high precision. At the same time, Friedman's tests revealed
      that all first-order and second-order statistical texture features changed
      significantly in response to therapy. Thereby, the majority of texture features
      showed significant changes in their values at all post-treatment time points
      relative to baseline. Bivariate analysis detected significant correlations
      between the great majority of texture features and the serum PSA levels. Thereby,
      three first-order and six second-order statistical features showed strong
      correlations with the serum PSA levels across time. CONCLUSION: The findings in
      the present work indicate that whole-tumor volumetric texture analysis may be
      utilized for response assessment in prostate cancer bone metastases. The approach
      may be used as a complementary measure for treatment monitoring in conjunction
      with averaged ADC values.

PMID- 29571796
TI  - Prognostic value of CT-derived left atrial and left ventricular measures in
      patients with acute chest pain: Methodological issue.

PMID- 29571797
TI  - Combined screening with mammography and ultrasound in a population-based
      screening program.
AB  - OBJECTIVES: To compare the performance of screening with mammography combined
      with ultrasound versus mammography alone in women at average risk for breast
      cancer. METHODS: 66,680 women underwent physician-performed ultrasound as an
      adjunct to screening mammography. Histological results and follow-up at one year
      were used as reference standard for sensitivity. Main outcome measures were
      cancer detection rate, sensitivity, recall rate, biopsy rate, and positive
      predictive value of biopsy for combined screening with mammography plus
      ultrasound versus mammography alone. RESULTS: The overall sensitivity of
      mammography only was 61.5% in women with dense breasts and 86.6% in women with
      non-dense breasts. The sensitivity of mammography plus ultrasound combined was
      81.3% in women with dense breasts and 95.0% in women with non-dense breasts.
      Adjunctive ultrasound increased the recall rate from 10.5 to 16.5 per 1000 women
      screened, and increased the biopsy rate from 6.3 to 9.3 per 1000 women screened.
      The positive predictive value of biopsy was 55.5% (95% CI 50.6%-60.3%) for
      mammography alone and 43.3 (95% CI 39.4%-47.3%) for combined mammography plus
      ultrasound. CONCLUSIONS: Supplemental ultrasound improves cancer detection in
      screening of women at average risk for breast cancer. Recall rates and biopsy
      rates can be kept within acceptable limits.

PMID- 29571798
TI  - Diagnostic performance of coronary CT angiography with ultra-high-resolution CT:
      Comparison with invasive coronary angiography.
AB  - PURPOSE: Recently, ultra-high-resolution computed tomography (U-HRCT) with a 0.25
      mm * 128-row detector was introduced. The purpose of this study was to evaluate
      the diagnostic performance of coronary CT angiography (CCTA) using U-HRCT.
      METHODS: This retrospective study included 38 consecutive patients with suspected
      coronary artery disease (CAD) who underwent CCTA with U-HRCT followed by invasive
      coronary angiography (ICA). Per-segment diameter stenosis was calculated.
      Diagnostic performance of CCTA relative to ICA as the reference standard was
      determined. For segments with >30% diameter stenosis, the correlation and
      agreement of percent diameter stenosis between CCTA and ICA were calculated.
      RESULTS: Obstructive CAD was observed in 65 segments (12%) of 51 vessels (45%) in
      32 patients (84%) during ICA. The per-patient, vessel, and segment analyses
      showed a sensitivity of 100% (95% confidence interval [CI], 95%-100%), 96% (95%
      CI: 89%-99%) and 95% (95% CI: 89%-98%), respectively, and a specificity of 67%
      (95% CI: 38%-67%), 81% (95% CI: 75%-83%) and 96% (95% CI: 96%-97%), respectively.
      The percentage of diameter stenosis, as determined by CCTA, demonstrated an
      excellent correlation with ICA (R = 0.90; 95% CI: 0.83-0.95) and a slight
      significant overestimation (mean: 4% +/- 7%, p < .01), with the agreed range of
      limits being +/- 16%. The median effective radiation dose for CCTA was 5.4 mSv
      (range: 2.9-18.0 mSv). CONCLUSIONS: CCTA with U-HRCT demonstrated an excellent
      correlation and agreement with ICA in the quantification of coronary artery
      stenosis.

PMID- 29571799
TI  - Measurement of pediatric regional cerebral blood flow from 6 months to 15 years
      of age in a clinical population.
AB  - OBJECTIVES: To investigate changes in cerebral blood flow (CBF) in gray matter
      (GM) between 6 months and 15 years of age and to provide CBF values for the
      brain, GM, white matter (WM), hemispheres and lobes. METHODS: Between 2013 and
      2016, we retrospectively included all clinical MRI examinations with arterial
      spin labeling (ASL). We excluded subjects with a condition potentially affecting
      brain perfusion. For each subject, mean values of CBF in the brain, GM, WM,
      hemispheres and lobes were calculated. GM CBF was fitted using linear, quadratic
      and cubic polynomial regression against age. Regression models were compared with
      Akaike's information criterion (AIC), and Likelihood Ratio tests. RESULTS: 84
      children were included (44 females/40 males). Mean CBF values were 64.2 +/- 13.8
      mL/100 g/min in GM, and 29.3 +/- 10.0 mL/100 g/min in WM. The best-fit model of
      brain perfusion was the cubic polynomial function (AIC = 672.7, versus
      respectively AIC = 673.9 and AIC = 674.1 with the linear negative function and
      the quadratic polynomial function). A statistically significant difference
      between the tested models demonstrating the superiority of the quadratic (p =
      0.18) or cubic polynomial model (p = 0.06), over the negative linear regression
      model was not found. No effect of general anesthesia (p = 0.34) or of gender (p =
      0.16) was found. CONCLUSION: we provided values for ASL CBF in the brain, GM, WM,
      hemispheres, and lobes over a wide pediatric age range, approximately showing
      inverted U-shaped changes in GM perfusion over the course of childhood.

PMID- 29571800
TI  - Central echogenic areas in thyroid nodules: Diagnostic performance in prediction
      of papillary cancer.
AB  - PURPOSE: To determine the diagnostic performance of the "central echogenic area"
      sonographic finding in differentiating papillary carcinomas from benign nodules
      and to how this finding may be used to improve fine needle aspiration(FNA)
      technique/utilization. MATERIALS AND METHODS: We retrospectively analyzed
      ultrasound guided FNAs of thyroid nodules between 1 and 3 cm for central
      echogenic areas. 92 patients (evenly distributed benign vs papillary carcinoma)
      were evaluated by a blinded reader for areas of non-shadowing homogenously
      echogenic centers within the nodules and correlated with FNA proven pathologic
      diagnosis. A selection of nodules with the central echogenic area finding were
      selected for further slide review to establish a pathologic basis for the
      finding. RESULTS: Diagnostic performance of the "central echogenic area" feature
      in papillary thyroid cancers was 52.2% sensitive and 91.3% specific for papillary
      thyroid carcinoma with a PPV of 85.7% and NPV of 65.6%. There was a significant
      correlation with a p < 0.01 between the central echogenic area finding and
      papillary carcinoma. On pathologic slide review, nodules with central echogenic
      areas consistently demonstrated a central scar with conglomerate fibrosis and
      very few viable cells. CONCLUSION: Despite its relatively low sensitivity, the
      central echogenic area finding is highly specific for papillary carcinoma of the
      thyroid and can be a useful sonographic finding in decisions regarding FNA.
      Additionally, due to the paucity of cells and high density of conglomerate
      fibrosis, central echogenic areas should be avoided during FNA to decrease the
      chance of an inadequate sample collection.

PMID- 29571801
TI  - Chest CT texture analysis for response assessment in systemic sclerosis.
AB  - PURPOSE: To evaluate the role of CT-textural features for monitoring lung
      involvement in subjects with systemic sclerosis(SSc) undergoing autologous stem
      cell transplantation(SCT) by comparison with semi-quantitative chest-CT,
      pulmonary function tests(PFT) and clinical parameters (modified Rodnan skin
      score[mRSS]). METHODS: In a retrospective single centre analysis, we identified
      23 consecutive subjects(11male) with SSc between 07/2005 and 11/2016 that
      underwent chest CTs before, 6 and 12 months post-SCT. Response to therapy was
      defined at 6 months after transplantation as stabilisation or improvement in FVC
      > 10% and DLCOSB > 10%. CT-texture analysis(CTTA) including mean, entropy and
      uniformity were calculated. RESULTS: PFT classified the subjects into
      responders(18/23;78%) and non-responders(5/23;22%). mRSS improved in responders
      from 28.46 +/- 9.53 to 15.70 +/- 10.07 6 months after auto-SCT(p = .001) whereas
      in non-responders no significant improvement was registered. Fibrosis score
      increased significantly(mean2.33 +/- 1.23 vs.1.41 +/- 0.78; p = .005) in non
      responders after 6 and 12months. Significant lower mean intensity and entropy of
      skewness and higher uniformity of skewness was found in responders vs. non
      responders at baseline. Significant changes in CTTA-parameters were found in both
      responders and non-responders at 6months and only in responders also at 12months
      post-SCT. CONCLUSIONS: Changes in CT-textural features after SCT are associated
      with visual CT evaluation of SSc-related lung abnormalities, but complementary
      provide information about therapy-induced, structural pulmonary changes.

PMID- 29571802
TI  - Evaluation of median nerve by shear wave elastography and diffusion tensor
      imaging in carpal tunnel syndrome.
AB  - PURPOSE: The aim of the current study is to investigate the diagnostic role of
      shear-wave elastography and diffusion tensor imaging in patients with carpal
      tunnel syndrome. MATERIAL AND METHODS: The study included a total of 77 wrists;
      18 normal, 35 wrists with mild, 9 wrists with moderate and 15 wrists with severe
      carpal tunnel syndrome. Elastography of the median nerve was performed by
      defining the boundaries of a segment of the nerve at sagittal plane at the level
      of proximal carpal row. Additionally, the cross-sectional area of the median
      nerve was evaluated. Fractional anisotropy and apparent diffusion coefficient
      measurements were carried out by placing region-of-interest at three levels: at
      pisiform bone (carpal tunnel inlet), mid carpal tunnel, and hook of hamate
      (carpal tunnel outlet). RESULTS: Patients with carpal tunnel syndrome had higher
      elasticity values of median nerve (53.0 kPa; IQR 40.8-77.0 kPa) compared to
      control subjects. (36.8 kPa; IQR 31.0-39.9 kPa) Patients with moderate-severe
      carpal tunnel syndrome had higher elasticity values (82 kPa; IQR 64.0-95.5 kPa)
      compared to patients with mild carpal tunnel syndrome. (44 kPa; IQR 32.5-59.5
      kPa) Patients with carpal tunnel syndrome had lower fractional anisotropy at mid
      carpal level (0.382; IQR 0.330-0.495) compared to the control group. (0.494; IQR
      0.434-0.537) Patients with moderate-severe carpal tunnel syndrome had lower
      fractional anisotropy values (0.366; IQR 0.331-0.407) and higher apparent
      diffusion coefficient values (1.509 mm2/s; IQR 1.374-1.733 mm2/s) compared to
      patients with mild carpal tunnel syndrome. (0,423; IQR 0.324-0.526 and 1.293
      mm2/s; IQR 0.967-1.514 mm2/s) CONCLUSION: Shear-wave elastography and diffusion
      tensor imaging are helpful imaging modalities in diagnosing carpal tunnel
      syndrome and assessing its severity.

PMID- 29571803
TI  - Tumor response to neoadjuvant chemotherapy in patients with esophageal cancer
      assessed with CT and FDG-PET/CT - RECIST 1.1 vs. PERCIST 1.0.
AB  - PURPOSE: We compared the response classification systems Response Evaluation
      Criteria in Solid Tumors (RECIST) 1.1 and Positron Emission Tomography Response
      Criteria in Solid Tumors (PERCIST) 1.0 for assessment of response to neoadjuvant
      chemotherapy in patients with esophageal cancer. MATERIALS AND METHODS: Prior to
      planned surgical resection, 62 patients with esophageal cancer underwent
      fluorodeoxyglucose (FDG)-PET/CT and contrast-enhanced CT examinations before and
      after receiving neoadjuvant chemotherapy. Primary tumor largest diameter, maximum
      standardized uptake value (SUVmax), peak lean body mass SUV (SULpeak), metabolic
      tumor volume (MTV), and total lesion glycolysis (TLG) were determined. Patients
      were divided into responders (grade 1b-3) and non-responders (grade 0-1a)
      according to pathological response. RESULTS: Concordance between RECIST 1.1 and
      PERCIST 1.0 for response classification was seen in 28 (45.2%) patients. For 18
      defined as responders, the number of metabolic responders (partial metabolic
      response + complete metabolic response) shown by PERCIST 1.0 was 17 and the
      number of anatomic responders (partial response + complete response) shown by
      RECIST 1.1 was 13. To distinguish responders from non-responders, the area under
      the receiver operating characteristics curve values for reduced primary tumor
      largest diameter, SUVmax, SULpeak, MTV, and TLG were 0.724, 0.775, 0.781, 0.756,
      and 0.759, respectively. An optimal percent decrease in largest diameter cut-off
      value of 39.2% was found to have 66.7% sensitivity and 70.5% specificity, while
      that for SULpeak of 55.8% was 77.8% and 75.0%, respectively. CONCLUSIONS: As
      compared to RECIST 1.1, PERSIST 1.0 may be more suitable for evaluation of
      neoadjuvant therapeutic response to esophageal cancer.

PMID- 29571804
TI  - Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines.
AB  - One of the key strategies to improve the prognosis of HCC, beside prevention, is
      to diagnose the tumor in early stages, when the patient is asymptomatic and the
      liver function is preserved, because in this clinical situation effective
      therapies with survival benefit can be applied. Imaging techniques are a key tool
      in the surveillance and diagnosis of HCC. Screening should be based in US every 6
      months and non-invasive diagnostic criteria of HCC based on imaging findings on
      dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical
      guidelines. The typical vascular pattern depicted by HCC on CT and or MRI
      consists on arterial enhancement, stronger than the surrounding liver (wash-in),
      and hypodensity or hyposignal intensity compared to the surrounding liver (wash
      out) in the venous phase. This has a sensitivity of around 60% with a 96-100%
      specificity. Major improvements on liver imaging have been introduced in the
      latest years, adding functional information that can be quantified: the use of
      hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted
      sequences in the standard protocols for liver MRI studies and new radiotracers
      for positron-emission tomography (PET). However, all them are still a matter of
      research prior to be incorporated in evidence based clinical decision making.
      This review summarizes the current knowledge about imaging techniques for the
      early diagnosis and staging of HCC, and it discusses the most relevant open
      questions.

PMID- 29571805
TI  - Imaging findings of hereditary renal tumors, a review of what the radiologist
      should know.
AB  - It is estimated that up to 8% of currently diagnosed renal cancers are part of a
      hereditary syndrome. The radiologist may be the first person to associate a renal
      tumor presenting during an imaging study to other manifestations of a hereditary
      syndrome. This diagnosis can have broad implications for the patient but also for
      other family members. This update reviews the current known associations and
      emerging mutations of hereditary renal cancers from a radiologist's perspective.
      Renal manifestations, as well as associated radiological findings and pitfalls
      are discussed. Additionally, screening and surveillance recommendations are also
      discussed to aid radiologists in the decision-making process for patient
      management.

PMID- 29571806
TI  - Pulmonary nodules: Assessing the imaging biomarkers of malignancy in a "coffee
      break".
AB  - INTRODUCTION: Although nodule volumetry is a recognized biomarker of malignancy
      in pulmonary nodules (PNs), caution is needed in its interpretation because of
      variables such as respiratory volume variation and inter-scan variability of up
      to 25%. CT Texture Analysis (CTTA) is a potential independent biomarker of
      malignancy but inter-scan variability and respiratory volume variation has not
      been assessed. METHODS: In this prospective cohort study, 40 patients (20 with an
      indeterminate PN and 20 with pulmonary metastases) underwent two LDCTs within a
      60-min period (the "Coffee-break") with the aim of assessing the repeatability of
      CTTA and semi-automated volume measurements. Texture features were extracted from
      each automatic contoured region surrounding the PN. Patients were also randomized
      to two inspiratory control groups: normal breath hold, and controlled lung volume
      to study the influence of inspiratory control on these measurements. RESULTS: The
      mean difference in volume between the two scans was 6.3%,SD:29.9%. The textural
      features displayed 95% CI below +/-17.8%, and were less variable than nodule
      volume (95%CI +/- 28.9%). All features had high repeatability, calculated by the
      concordance correlation coefficient, (0.84 <= CCC <= 0.99). All measurements were
      more repeatable for the controlled lung volume group than the normal breath-hold
      group. CONCLUSION: CTTA repeatability was comparable to automatic volumetric
      measurements, and appears to be improved using controlled volume breath holding.

PMID- 29571807
TI  - Cumulative effective dose and cancer risk for pediatric population in repetitive
      full spine follow-up imaging: How micro dose is the EOS microdose protocol?
AB  - OBJECTIVE: To evaluate and to obtain analytic formulation for the calculation of
      the effective dose and associated cancer risk using the EOS microdose protocol
      for scoliotic pediatric patients undergoing full spine imaging at different age
      of exposure; to demonstrate the microdose protocol capable of delivering lesser
      radiation dose and hence of further reducing cancer risk induction when compared
      with the EOS low dose protocol; to obtain cumulative effective dose and cancer
      risk for both genders scoliotic pediatrics of US and Hong Kong population using
      the microdose protocol. METHODS: Organ absorbed doses of full spine exposed
      scoliotic pediatric patients have been simulated with the use of EOS microdose
      protocol imaging parameters input to the Monte Carlo software PCXMC. Gender and
      age specific effective dose has been calculated with the simulated organ absorbed
      dose using the ICRP-103 approach. The associated radiation induced cancer risk,
      expressed as lifetime attributable risk (LAR), has been estimated according to
      the method introduced in the Biological Effects of Ionizing Radiation VII report.
      Values of LAR have been estimated for scoliotic patients exposed repetitively
      during their follow up period at different age for US and Hong Kong population.
      RESULTS: The effective doses of full spine imaging with simultaneous
      posteroanterior and lateral projection for patients exposed at the age between 5
      and 18 years using the EOS microdose protocol have been calculated within the
      range of 2.54-14.75 MUSv. The corresponding LAR for US and Hong Kong population
      was ranged between 0.04 * 10-6 and 0.84 * 10-6. Cumulative effective dose and
      cancer risk during follow-up period can be estimated using the results and are of
      information to patients and their parents. CONCLUSION: With the use of computer
      simulation and analytic formulation, we obtained the cumulative effective dose
      and cancer risk at any age of exposure for pediatric patients of US and Hong Kong
      population undergoing repetitive microdose protocol full spine imaging. Girls
      would be at a statistically significant higher cumulative cancer risk than boys
      undergoing the same microdose full spine imaging protocol and the same follow-up
      schedule.

PMID- 29571808
TI  - Comparison of the effect of radiation exposure from dual-energy CT versus single
      energy CT on double-strand breaks at CT pulmonary angiography.
AB  - PURPOSE: To compare the effect of dual-source dual-energy CT versus single-energy
      CT on DNA double-strand breaks (DSBs) in blood lymphocytes at CT pulmonary
      angiography (CTPA). METHODS AND MATERIALS: Sixty-two patients underwent either
      dual-energy CTPA (Group 1: n = 21, 80/Sn140 kVp, 89/38 mAs; Group 2: n = 20,
      100/Sn140 kVp, 89/76 mAs) or single-energy CTPA (Group 3: n = 21, 120 kVp, 110
      mAs). Blood samples were obtained before and 5 min after CTPA. DSBs were assessed
      with fluorescence microscopy and Kruskal-Walls tests were used to compare DSBs
      levels among groups. Volume CT dose index (CTDIvol), dose length product (DLP)
      and organ radiation dose were compared using ANOVA. RESULTS: There were increased
      excess DSB foci per lymphocyte 5 min after CTPA examinations in three groups
      (Group 1: P = .001; Group 2: P = .001; Group 3: P = .006). There were no
      differences among groups regarding excess DSB foci/cell and percentage of excess
      DSBs (Group 1, 23%; Group 2, 24%; Group 3, 20%; P = .932). CTDIvol, DLP and organ
      radiation dose in Group 1 were the lowest among the groups (all P < .001).
      CONCLUSION: DSB is increased following dual-source and single-source CTPA, while
      dual-source dual-energy CT protocols do not increase the estimated radiation dose
      and also do not result in a higher incidence of DNA DSBs in patients undergoing
      CTPA.

PMID- 29571809
TI  - Vessel suppressed chest Computed Tomography for semi-automated volumetric
      measurements of solid pulmonary nodules.
AB  - OBJECTIVE: To evaluate whether vessel-suppressed computed tomography (VSCT) can
      be reliably used for semi-automated volumetric measurements of solid pulmonary
      nodules, as compared to standard CT (SCT) MATERIAL AND METHODS: Ninety-three SCT
      were elaborated by dedicated software (ClearRead CT, Riverain Technologies,
      Miamisburg, OH, USA), that allows subtracting vessels from lung parenchyma. Semi
      automated volumetric measurements of 65 solid nodules were compared between SCT
      and VSCT. The measurements were repeated by two readers. For each solid nodule,
      volume measured on SCT by Reader 1 and Reader 2 was averaged and the average
      volume between readers acted as standard of reference value. Concordance between
      measurements was assessed using Lin's Concordance Correlation Coefficient (CCC).
      Limits of agreement (LoA) between readers and CT datasets were evaluated.
      RESULTS: Standard of reference nodule volume ranged from 13 to 366 mm3. The mean
      overestimation between readers was 3 mm3 and 2.9 mm3 on SCT and VSCT,
      respectively. Semi-automated volumetric measurements on VSCT showed substantial
      agreement with the standard of reference (Lin's CCC = 0.990 for Reader 1; 0.985
      for Reader 2). The upper and lower LoA between readers' measurements were (16.3, 
      22.4 mm3) and (15.5, -21.4 mm3) for SCT and VSCT, respectively. CONCLUSIONS: VSCT
      datasets are feasible for the measurements of solid nodules, showing an almost
      perfect concordance between readers and with measurements on SCT.

PMID- 29571810
TI  - The Unusual Presence of Gas From a Puncture Wound: A Case Report.
AB  - The presence of gas within soft tissues as suggested by plain film radiographs
      and magnetic resonance imaging is usually sufficient evidence for a gas-producing
      bacterial infection. A thorough clinical examination and history and tissue
      culture are necessary to better determine the source of the gas. However, despite
      the unremarkable physical examination findings, the present case of a plantar
      puncture wound rapidly developed gas in the tissues and warranted surgical
      exploration and repair. Delaying treatment in any case of potential gas gangrene
      can be limb- and life-threatening. Only later was it revealed by the patient's
      husband that the wound might have been contaminated soon after the injury from a
      source other than the puncture, which led to the early presentation of gas on the
      imaging studies.

PMID- 29571811
TI  - Spontaneous symmetry breaking of population: Stochastic Lotka-Volterra model for
      competition among two similar preys and predators.
AB  - The celebrated Lotka-Volterra (LV) model is vastly used to describe the simple
      competition between prey and predator populations. The stochastic LV model, for
      its turn, considers the competition among two similar prey and two similar
      predator populations, with each group being described by identical mathematical
      equations. However, each of these groups differs in stochastic fluctuations,
      which are interpreted as small variations in each species' specimens (Genetic
      Diversity and Phenotypic Expression Diversity) and environmental conditions. The
      relative statistical variation presented is inversely proportional to the square
      root of the amount of specimens in each population. The model begins with two
      prey and two predator groups and, after a transient time, is reduced to one
      element of each group, returning to the classic LV system. That is, the model
      ends in asymmetric states despite starting from an initial symmetric condition
      without population excess. Spontaneous population symmetry breaking without
      population excess was obtained using the stochastic method. For its turn, the
      deterministic method could be used to analyze such breaking by forcing a
      perturbative fluctuation or adding little excess to one population, but the
      stochastic method can simulate such break in symmetry naturally.

PMID- 29571812
TI  - Vitality heterogeneity in the Strehler-Mildvan theory of mortality.
AB  - In this paper the Strehler-Mildvan theory of mortality and aging is generalised
      to cover heterogeneity effects in the population. The theory is based on the
      concept of environmental shocks that cause death of an individual when exceeding
      its vitality. Heterogeneity is introduced via the value of the vitality of an
      individual at birth. The main result of the paper is an expression for the
      observed mortality rate of the heterogeneous population. This mortality rate
      grows according to Gompertz's Law at midlife-ages, then its growth declines,
      levelling off at high ages. This behaviour is qualitatively consistent with real
      mortality rates, which is illustrated for period data of Japanese females in the
      years 1947, 1967, 1987 and 2007. Finally, the duality between a continuous SM
      version and the rho - gamma - Gompertz model is discussed.

PMID- 29571813
TI  - Analysis of the peristaltic-ciliary flow of Johnson-Segalman fluid induced by
      peristalsis-cilia of the human fallopian tube.
AB  - The present prospective theoretical analysis concerns with the peristalsis-cilia
      induced transport of a developing embryo from ampulla to intramural, in the human
      fallopian tube. A model of peristalsis-cilia induced flow of the Johnson-Segalman
      fluid within fallopian tubal fluid in a finite two dimensional narrow tube is
      developed. We solved highly non-linear PDE emerging from the modeling of proposed
      model using perturbation method. The series expressions for flow variables like
      axial and radial velocities, pressure gradient, stream function, volume flow rate
      and time mean volume flow rate are derived. The numerical integration is
      performed for appropriate residue time over tube length and pressure difference
      over wavelength. The analysis delineated that, involved parameters and constants
      have vice versa effects on axial velocity and appropriate residue time over tube
      length. Striking features of the pumping characteristics and the trapping
      phenomenon are discussed in detail. Furthermore, comparison of the peristaltic
      flow with the peristaltic-ciliary flow and Johnson-Segalman fluid with the
      linearly viscous fluid is made. It is revealed that appropriate residue time of
      the Johnson-Segalman fluid in the narrow tube is 3-4 days, which agreed with the
      time taken by the developing embryo from ampulla to intramural, in the human
      fallopian tube.

PMID- 29571814
TI  - Modeling the lake eutrophication stochastic ecosystem and the research of its
      stability.
AB  - In the reality, the lake system will be disturbed by stochastic factors including
      the external and internal factors. By adding the additive noise and the
      multiplicative noise to the right-hand sides of the model equation, the additive
      stochastic model and the multiplicative stochastic model are established
      respectively in order to reduce model errors induced by the absence of some
      physical processes. For both the two kinds of stochastic ecosystems, the authors
      studied the bifurcation characteristics with the FPK equation and the Lyapunov
      exponent method based on the Stratonovich-Khasminiskii stochastic average
      principle. Results show that, for the additive stochastic model, when control
      parameter (i.e., nutrient loading rate) falls into the interval [0.388644,
      0.66003825], there exists bistability for the ecosystem and the additive noise
      intensities cannot make the bifurcation point drift. In the region of the
      bistability, the external stochastic disturbance which is one of the main
      triggers causing the lake eutrophication, may make the ecosystem unstable and
      induce a transition. When control parameter (nutrient loading rate) falls into
      the interval (0,  0.388644) and (0.66003825,  1.0), there only exists a stable
      equilibrium state and the additive noise intensity could not change it. For the
      multiplicative stochastic model, there exists more complex bifurcation
      performance and the multiplicative ecosystem will be broken by the multiplicative
      noise. Also, the multiplicative noise could reduce the extent of the bistable
      region, ultimately, the bistable region vanishes for sufficiently large noise.
      What's more, both the nutrient loading rate and the multiplicative noise will
      make the ecosystem have a regime shift. On the other hand, for the two kinds of
      stochastic ecosystems, the authors also discussed the evolution of the ecological
      variable in detail by using the Four-stage Runge-Kutta method of strong order
      gamma=1.5. The numerical method was found to be capable of effectively explaining
      the regime shift theory and agreed with the realistic analyze. These conclusions
      also confirms the two paths for the system to move from one stable state to
      another proposed by Beisner et al. [3], which may help understand the occurrence
      mechanism related to the lake eutrophication from the view point of the
      stochastic model and mathematical analysis.

PMID- 29571815
TI  - Extracorporeal lithotripsy of salivary gland stone: A 55 patients study.
AB  - Sialolithiasis are the most frequent salivary gland disease, mainly affecting the
      submandibular gland. With the advent of minimally invasive techniques, total
      salivary gland removal should not be considered as the first-line treatment
      anymore. Extracorporeal Shock Wave Lithotripsy (ESWL) is an alternative to
      surgery preserving the gland. The objective of our retrospective study was to
      evaluate the efficiency of ESWL on pain and obstructive syndrome in patients
      suffering from sialolithiasis. The global result felt by the patients was also
      considered. All patients treated between October 2009 and July 2016 for
      sialolithiasis by ESWL in our department were included. They were divided into
      two groups according to the concerned gland: a parotid gland (PG) and a
      submandibular gland (SMG) group. Our retrospective telephone questionnaire
      consisted in 4 questions about their symptomatology before and after ESWL,
      including pain self-evaluation before and after treatment. They were finally
      asked to evaluate the global result of the ESWL treatment: excellent, good, mean,
      or poor. In total, 55 patients were included in this study, 38 patients in PG
      group and 17 patients in SMG group. We observed a decrease of pain and
      obstructive syndrom after ESWL procedure in both groups. Better results were
      found on the obstructive syndrome in the PG group. Very few side-effects were
      reported by patients. Given that it has very few side effects, ESWL can easily be
      considered as first line treatment for sialolithiasis to avoid heavier treatments
      such as surgery. It should be the first-line treatment for symptomatic parotid
      sialolithiases. The treatment of symptomatic submandibular sialolithiases depends
      on the topography of the lithiasis.

PMID- 29571816
TI  - Does mandibular third molar have an impact on dental mandibular anterior
      crowding? A literature review.
AB  - Mandibular dental anterior crowding is a common multi-factorial phenomenon. The
      involvement of the lower third molar remains unclear. These pending questions led
      us to conduct a literature review to evaluate the impact of the lower third molar
      on mandibular dental anterior crowding. Twelve articles were selected, published
      from 1974 to 2014. Four studies were prospective. Sample size ranged from 30 to
      9044. The average age was 20.56 years old. Seven studies considered patient with
      orthodontic treatment. The studies compared two to four groups. Studying tools
      were radiographs, casts and clinical examinations. Little's irregularity index,
      TSALD and Ganss ratio were used. In total, 83% of articles (n=10/12) did not find
      any significant relationship between lower third molar and mandibular dental
      anterior crowding. However, methods and designs of these studies being
      questionable, a definite conclusion on the impact of mandibular third molar on
      mandibular dental anterior crowding cannot be set.

PMID- 29571817
TI  - Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for
      type 2 poliovirus outbreak response: an open-label, randomised controlled trial.
AB  - BACKGROUND: Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated
      poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We
      aimed to assess the effect of two mOPV2 doses on the type 2 immune response by
      varying the time interval between mOPV2 doses and IPV co-administration with
      mOPV2. METHODS: We did a randomised, controlled, parallel, open-label, non
      inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy
      infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1)
      to receive two mOPV2 doses (each dose consisting of two drops [0.1 mL in total]
      of about 105 50% cell culture infectious dose of type 2 Sabin strain) at
      intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks
      with IPV (0.5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D
      antigen units], and type 3 [Saukett, 32 D-antigen units]) administered
      intramuscularly with the first mOPV2 dose. We used block randomisation, randomly
      selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We
      concealed randomisation assignment from staff managing participants in opaque,
      sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked
      to assignment after the randomisation envelope was opened. Laboratory staff
      analysing sera were masked to assignment, but investigators analysing data and
      assessing outcomes were not. The primary outcome was type 2 immune response
      measured 4 weeks after mOPV2 administration. The primary modified intention-to
      treat analysis included participants with testable serum samples before and after
      vaccination. A non-inferiority margin of 10% and p=0.05 (one-tailed) was used.
      This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed
      to accrual. FINDINGS: Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned
      760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks
      (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune responses after two
      mOPV2 doses were observed in 161 (93%) of 173 infants with testable serum samples
      in the 1 week group, 169 (96%) of 177 in the 2 week group, and 176 (97%) of 181
      in the 4 week group. 1 week and 2 week intervals between two mOPV2 doses were non
      inferior to 4 week intervals because the lower bound of the absolute differences
      in the percentage of immune responses were greater than -10% (-4.2% [90% CI -7.9
      to -0.4] in the 1 week group and -1.8% [-5.0 to 1.5] in the 2 week group vs the 4
      week group). The immune response elicited by two mOPV2 doses 4 weeks apart was
      not different when IPV was added to the first dose (176 [97%] of 182 infants with
      IPV vs 176 [97%] of 181 without IPV; p=1.0). During the trial, two serious
      adverse events (pneumonia; one [1%] of 186 patients in the 1 week group and one
      [1%] of 182 in the 4 week group) and no deaths were reported; the adverse events
      were not attributed to the vaccines. INTERPRETATION: Administration of mOPV2 at
      short intervals does not interfere with its immunogenicity. The addition of IPV
      to the first mOPV2 dose did not improve poliovirus type 2 immune response.
      FUNDING: US Centers for Disease Control and Prevention.

PMID- 29571818
TI  - Eradicating polio with a vaccine we must stop using.

PMID- 29571819
TI  - Reliability evaluation of inter-eminence line, Akagi and Dalury lines for
      intraoperative tibial rotation: An osteology-based study.
AB  - BACKGROUND: This large osteology study examined the reliability, reproducibility
      and correlation between previously described tibial tray rotation alignment lines
      (including Akagi and Dalury lines). In addition, it described a novel inter
      eminence line utilising the tibial plateau inter-condylar eminences as a
      landmark. METHODS: A total of 214 post-medieval (18-19th centuries) skeletal
      tibia were examined. The inter/intra-observer variation and correlation between
      reference lines were measured. RESULTS: Inter-observer reproducibility was
      excellent and there were no differences between Akagi, Dalury, and inter-eminence
      lines. Similarly, intra-observer reliability was excellent for Akagi, Dalury, and
      inter-eminence lines. Qualitative review of tibial inter-condylar eminences
      suggested that these could be easily identifiable. When taking the medial angle
      from a medial-lateral reference line, the Akagi line showed a mean of 96.90
      degrees  (+/-10.27), inter-eminence line 94.52 degrees  (+/-12.84), and Dalury
      line 88.06 degrees  (+/-11.75). The angle produced by the Dalury line was
      significantly different from both the Akagi and inter-eminence lines (P<=0.001).
      The Akagi line and inter-eminence line showed a strong correlation (r=0.74). The
      Dalury line showed a weaker correlation with both the Akagi line (r=0.69) and
      inter-eminence line (r=0.40). CONCLUSION: This study suggested that tibial
      rotation lines showed excellent intra/inter-observer reliability and
      reproducibility. The novel and easily drawn inter-eminence line showed strong
      correlation with the Akagi line and could be used for tibial tray rotational
      alignment in total knee arthroplasty.

PMID- 29571820
TI  - Universal screening for foetal growth restriction.
AB  - Foetal growth restriction (FGR) is a major cause of morbidity and mortality.
      Clinical methods for identifying women whose pregnancies are affected by FGR do
      not perform well. Despite this, the current approach to screening includes the
      clinical assessment of risk and targeted use of ultrasound. Universal screening
      of women using ultrasound has not been shown to improve outcomes in randomised
      controlled trials and, when implemented nationally in France, appeared mostly to
      change outcomes for the worse through the effect of iatrogenic prematurity on
      false positives. Research is currently focused on the development of screening
      tests with higher sensitivity and specificity, for example, by combining
      ultrasound with placental biomarkers. The diagnostic tests employed should be
      identified through high-quality research that investigates the diagnostic
      accuracy of the tests, and this will usually involve blinding of the results.
      Therefore, future trials of screening and intervention will require careful
      planning. Moreover, if trials are to be powered for perinatal death, large sample
      sizes will be required.

PMID- 29571821
TI  - Care of the growth-restricted newborn.
AB  - With the first 1,000 days of life proving to be a critical window of opportunity
      for physical and cognitive growth and development, an optimal intrauterine
      environment is vital. If fetus needs are compromised prenatally, there is an
      increased risk of intrauterine growth restriction (IUGR), and infants being born
      premature, low birth weight (LBW), or small-for-gestational age (SGA).
      Specialized care of these high-risk infants is necessary in terms of
      preconception interventions, resuscitation, thermoregulation, nutritional support
      and kangaroo mother care. Significant evidence supports exclusive breastfeeding
      as the standard of care for feeding SGA, preterm, LBW and very low birth weight
      infants. Expressed milk or donor milk may also require fortification, to meet
      higher nutrient needs of these newborns. Future research should address the gap
      in the literature on specific care of term and preterm IUGR and or SGA infants,
      and strengthening evidence for human milk bank models and emollient care.

PMID- 29571822
TI  - Neonatal maternal separation leads to a dampening of inflammation-related
      mechanical and thermal hypersensitivity in juvenile rats.
AB  - Early life stress (ELS) constitutes a risk factor for the later development of
      psychopathological disorders partly displaying pain comorbidity. Since ELS may
      hence be expected to have an impact on pain processing the present study
      investigates whether ELS could be a factor of vulnerability or resilience against
      an enhancement of noxious sensitivity in the framework of inflammatory pain in
      later life. Rats were exposed to the maternal separation (MS) paradigm, an
      established ELS model. At adulthood, corticosterone levels and anxiety-related
      behaviors were evaluated. Subsequently, paw edema, noxious mechanical and thermal
      sensitivity were measured prior and during an inflammation induced by
      intraplantar injection of Complete Freunds Adjuvant (CFA). The open field test
      and the corticosterone measures showed no effect of MS. MS did not change
      mechanical thresholds prior to inflammation but reduced mechanical hyperalgesia
      after CFA-injection. MS animals did however present shorter latencies to display
      nocifensive behaviors compared to controls (CON). Furthermore, in CON but not MS,
      the repetitive noxious heat testing induced a decrease in reaction latencies.
      Moreover, MS dampened CFA-induced heat hyperalgesia. Altogether, our results
      suggest that ELS may have a protective impact on inflammatory pain.

PMID- 29571823
TI  - Dexmedetomidine promotes the recovery of neurogenesis in aged mouse with
      postoperative cognitive dysfunction.
AB  - Recently, growing evidence has demonstrated Dexmedetomidine (Dex) a promising
      intervene preventing postoperative cognitive decline (POCD) following surgery,
      which is associated with neuroinflammation leading to neuronal apoptosis and
      deregulated neurogenesis. Previous studies suggested the anti-inflammation and
      anti-neuroapoptosis action of Dex. Therefore we hypothesize the promoting
      neurogenesis of Dex linked to stimulating BDNF and subsequent p-MPAK production
      in a rat model of POCD. In the present study, the POCD animal model was
      established by performing an exploratory laparotomy under isoflurane anaesthesia
      in old rats, utilizing which Dex response is confirmed by behavioural tests.
      Inflammatory biomarkers as IL-1beta and TNF-alpha, mature neuron percentage
      measured by doublecortin staining (DCX), promoting factors as brain derived
      growth factor (BDNF), phosphorylated cAMP response element binding protein (CREB)
      and proteins of kinase A (PKA), MAPK production as p-P38-MAPK protein express
      were measured. Herein, we showed that surgery reduced DCX-positive neurons and
      expression of BDNF representing neurogenesis profoundly. As expected, Dex rescued
      the associated cognitive impairment and inflammatory changes, as well as up
      regulated expression of BDNF, PKA, p-CREB/CREB and following p-P38-MAPK
      regulation. Our results confirmed the protective Dex response and indicated the
      proneurogenesis role of it as well, suggesting the mechanism of beneficial
      effects of Dex to prevent POCD.

PMID- 29571825
TI  - The use of computed tomography tractography in anterior abdominal stab wounds.

PMID- 29571824
TI  - Dose-dependent reduction in cocaine-induced locomotion by Clozapine-N-Oxide in
      rats with a history of cocaine self-administration.
AB  - Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are novel
      tools for the dissection of circuitry mediating behavior and neural function.
      Designer receptors based on the muscarinic M3 and M4 subtypes were designed to be
      activated by clozapine-N-oxide (CNO), a ligand previously shown to be an inert
      metabolite of clozapine. However, recent work in rats has shown that CNO is
      reverse metabolized to its parent compound. Furthermore, CNO administration (5
      mg/kg IP) attenuates amphetamine-induced locomotion and the evoked dopamine
      response that accompanies it. As these systems are routinely used to probe the
      neurocircuitry underlying cocaine-seeking behavior, here we sought to determine
      whether CNO would have similar effects on cocaine-induced locomotion in rats with
      a history of cocaine self-administration. In order for muscarinic-based DREADDs
      to be utilized for the dissection of circuitry underlying behavioral responses to
      cocaine, the doses of CNO administered to induce DREADD signaling must themselves
      have no effect on cocaine-induced behavior. Male Sprague-Dawley rats self
      administered cocaine (0.35 mg/infusion) for 12 days, followed by 14-21 days of
      instrumental extinction training. Rats then underwent locomotor testing. CNO (0,
      3, or 5 mg/kg) was injected (utilizing a within-subjects design), followed 20 min
      later by cocaine (10 mg/kg IP). Locomotion was monitored for the following 120
      min. We found that the 5, but not the 3 mg/kg, dose of CNO reduced cocaine
      induced locomotion. Thus, studies utilizing DREAADs to probe cocaine-induced
      behavior should consider these findings when choosing a dose of CNO and include
      non-DREADD CNO controls.

PMID- 29571826
TI  - Is computed tomography tractography reliable in patients with anterior abdominal
      stab wounds?

PMID- 29571827
TI  - Adjusting D-dimer cutoffs: Brief literature summary and issues in clinical use.

PMID- 29571828
TI  - Low-dose (2-mSv) computed tomography for suspected appendicitis: Applicability in
      an emergency department.
AB  - OBJECTIVES: To document the level of interobserver agreement and compare the
      diagnostic performances of emergency physicians and radiologists at interpreting
      low radiation CT images of acute appendicitis in adolescents and young adults.
      METHODS: One hundred and seven adolescents and young adult patients (aged 15 to
      44years) that underwent 2-mSv low-dose CT for suspected acute appendicitis
      between June and December in 2013 were enrolled in this retrospective study.
      Three emergency physicians and three radiologists with different experiences of
      low-dose CT independently reviewed CT images. These six physicians rated the
      likelihood of acute appendicitis using a 5-point Likert scale. We calculated
      interobserver agreement and compared the diagnostic performances between
      emergency physicians and radiologists. And diagnostic confidence was also
      assessed using the likelihood of acute appendicitis. RESULTS: Acute appendicitis
      was pathologically confirmed in 42 patients (39%); the remaining 65 patients were
      considered not to have appendicitis. Fleiss' Kappa for reliability of agreement
      between emergency physicians and radiologists for the diagnosis of acute
      appendicitis was 0.720 (95% confidence intervals (CI), 0.685-0.726). Pooled areas
      under the receiver operating characteristics curve (AUC) for a diagnosis of
      appendicitis were 0.904 and 0.944 for emergency physicians and radiologists,
      respectively, and these AUC values were not significantly different (95%
      confidence interval, -0.087, 0.007; p=0.0855). CONCLUSION: The emergency
      physicians and radiologists showed good interobserver agreement and comparable
      diagnostic performances for appendicitis in adolescents and adults using low-dose
      CT images. Low-dose CT could be a useful tool for the diagnosis of appendicitis
      by emergency physicians.

PMID- 29571829
TI  - Corrigendum to "Shedder status-An analysis of self and non-self DNA in multiple
      handprints by the same individuals over time" [Forensic Sci. Int. Genet. 23
      (2016) 190-196].

PMID- 29571830
TI  - Impact of Incidence and Progression of Diabetic Retinopathy on Vision-Specific
      Functioning.
AB  - PURPOSE: To investigate the independent impact of the incidence and progression
      of diabetic retinopathy (DR) on visual functioning (VF). DESIGN: Population-based
      cohort study. PARTICIPANTS: A total of 518 participants aged 40 to 80 years
      (baseline visit 2007-2009 and second visit 6 years later, 2013-2015), with
      diabetes, clinical data, and VF information at both visits. MAIN OUTCOME
      MEASURES: VF-7 scores, converted to interval-level person measures (in logits)
      using Rasch analysis. METHODS: Incident DR was defined using the Modified Airlie
      House classification as "none or minimal" DR at baseline and at least mild
      nonproliferative DR at follow-up; incident vision-threatening DR (VTDR; severe
      nonproliferative DR, proliferative DR, and/or clinically significant macular
      edema) as no VTDR at baseline, and present at follow-up; and DR progression as at
      least a 1-step worsening in DR at follow-up from mild or worse status at
      baseline. The longitudinal associations between incident DR, VTDR, and DR
      progression, as well as change in composite and individual item scores of VF,
      were assessed using multivariable linear regression models. RESULTS: Of the 518
      participants (mean age +/- standard deviation [SD] 59.8+/-9.0 years; 47.7%
      female), 42 (9.8%), 14 (2.8%), and 32 (42.7%) had incident DR, incident VTDR, and
      DR progression, respectively, at follow-up. In models adjusting for traditional
      confounders, persons with incident DR and VTDR had a 13.7% (beta = -0.60; 95%
      confidence interval [CI], -0.96 to -0.24; P = 0.001) and 23% (beta = -1.00; 95%
      CI, -1.61 to -0.38; P = 0.001) reduction in mean VF scores at follow-up.
      Furthermore, individuals with incident DR had similar independent reductions in
      scores for 7 individual items of the VF-7, whereas those with incident VTDR had
      the largest reductions for activities like cooking (31%; P = 0.003), reading the
      newspaper (29.6%; P < 0.001), and seeing street signs (28%, P = 0.001) at follow
      up. Progression of DR was not independently associated with change in overall VF
      (beta = -0.18; 95% CI, -1.00, 0.64; P = 0.660). CONCLUSIONS: Incident DR,
      particularly vision-threatening stages, has a substantial negative impact on
      people's overall vision-dependent functioning and specific activities such as
      cooking, seeing street signs, and reading the newspaper. Our findings reinforce
      the need for strategies to prevent or delay the development of DR.

PMID- 29571831
TI  - Cost Evaluation of Laser versus Intravitreal Aflibercept for Proliferative
      Diabetic Retinopathy.

PMID- 29571832
TI  - Clinical Prediction Performance of Glaucoma Progression Using a 2-Dimensional
      Continuous-Time Hidden Markov Model with Structural and Functional Measurements.
AB  - PURPOSE: Previously, we introduced a state-based 2-dimensional continuous-time
      hidden Markov model (2D CT HMM) to model the pattern of detected glaucoma changes
      using structural and functional information simultaneously. The purpose of this
      study was to evaluate the detected glaucoma change prediction performance of the
      model in a real clinical setting using a retrospective longitudinal dataset.
      DESIGN: Longitudinal, retrospective study. PARTICIPANTS: One hundred thirty-four
      eyes from 134 participants diagnosed with glaucoma or as glaucoma suspects
      (average follow-up, 4.4+/-1.2 years; average number of visits, 7.1+/-1.8).
      METHODS: A 2D CT HMM model was trained using OCT (Cirrus HD-OCT; Zeiss, Dublin,
      CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and
      visual field index (VFI) or mean deviation (MD; Humphrey Field Analyzer; Zeiss).
      The model was trained using a subset of the data (107 of 134 eyes [80%])
      including all visits except for the last visit, which was used to test the
      prediction performance (training set). Additionally, the remaining 27 eyes were
      used for secondary performance testing as an independent group (validation set).
      The 2D CT HMM predicts 1 of 4 possible detected state changes based on 1 input
      state. MAIN OUTCOME MEASURES: Prediction accuracy was assessed as the percentage
      of correct prediction against the patient's actual recorded state. In addition,
      deviations of the predicted long-term detected change paths from the actual
      detected change paths were measured. RESULTS: Baseline mean +/- standard
      deviation age was 61.9+/-11.4 years, VFI was 90.7+/-17.4, MD was -3.50+/-6.04 dB,
      and cRNFL thickness was 74.9+/-12.2 MUm. The accuracy of detected glaucoma change
      prediction using the training set was comparable with the validation set (57.0%
      and 68.0%, respectively). Prediction deviation from the actual detected change
      path showed stability throughout patient follow-up. CONCLUSIONS: The 2D CT HMM
      demonstrated promising prediction performance in detecting glaucoma change
      performance in a simulated clinical setting using an independent cohort. The 2D
      CT HMM allows information from just 1 visit to predict at least 5 subsequent
      visits with similar performance.

PMID- 29571833
TI  - Coffee Consumption and Incident Kidney Disease: Results From the Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Moderate coffee consumption has been suggested to be associated with
      lower risk for chronic conditions such as diabetes, a major precursor to chronic
      kidney disease (CKD). However, the association between coffee and CKD has not
      been fully established. STUDY DESIGN: Prospective cohort study. SETTING &
      PARTICIPANTS: 14,209 participants aged 45 to 64 years from the Atherosclerosis
      Risk in Communities (ARIC) Study. PREDICTORS: Coffee consumption (cups per day)
      was assessed at visits 1 (1987-1989) and 3 (1993-1995) using food frequency
      questionnaires. OUTCOMES: Incident CKD defined as estimated glomerular filtration
      rate < 60mL/min/1.73m2 accompanied by >=25% estimated glomerular filtration rate
      decline, CKD-related hospitalization or death, or end-stage renal disease.
      RESULTS: There were 3,845 cases of incident CKD over a median of 24 years of
      follow-up. Men, whites, current smokers, and participants without comorbid
      conditions were more likely to consume higher amounts of coffee per day. After
      adjustment for demographic, clinical, and dietary factors, higher categories of
      coffee consumption were associated with lower risk for incident CKD compared with
      those who never consumed coffee (HR for <1 cup per day, 0.90 [95% CI, 0.82-0.99];
      1-<2 cups per day, 0.90 [95% CI, 0.82-0.99]; 2-<3 cups per day, 0.87 [95% CI,
      0.77-0.97]; and >=3 cups per day, 0.84 [95% CI, 0.75-0.94]). In continuous
      analysis, for each additional cup of coffee consumed per day, risk for incident
      CKD was lower by 3% (HR, 0.97; 95% CI, 0.95-0.99; P<0.001). LIMITATIONS: Self
      reported coffee consumption and observational design. CONCLUSIONS: Participants
      who drank higher amounts of coffee had lower risk for incident CKD after
      adjusting for covariates. Coffee consumers may not be at adverse risk for kidney
      disease.

PMID- 29571834
TI  - Vaccine Biomarkers: In Search of a Goldilocks Approach.

PMID- 29571835
TI  - Bedaquiline Phenotypic and Genotypic Susceptibility Testing, Work in Progress!

PMID- 29571836
TI  - Ligands Switch Model for Pollen-Tube Integrity and Burst.
AB  - In flowering plants, pollen tubes deliver and release the immotile sperms to the
      female gametes for fertilization, but mechanisms remain unclear. New results show
      that the RALF family peptides control pollen-tube integrity and burst by binding
      to CrRLK1L family receptors and cell wall leucine-rich repeat extensins.

PMID- 29571837
TI  - Increased building block access through collaboration.

PMID- 29571838
TI  - Multidrug-resistant infections in long-term care facilities: extended-spectrum
      beta-lactamase-producing Enterobacteriaceae and hypervirulent antibiotic
      resistant Clostridium difficile.
AB  - Infections due to multidrug-resistant (MDR) organisms in long-term care
      facilities (LTCFs) residents constitute a public health concern. This multicenter
      study investigated the frequency of ESBL-producing pathogens and MDR Clostridium
      difficile in clinical specimens from LTCF residents in Italy. During October 2014
      March 2015, all urine and diarrheic fecal samples from LTCF residents (>=65
      years) with suspected urinary tract infection or C. difficile infection,
      respectively, received for diagnosis by 4 hospital laboratories located in
      different cities were analyzed. Antibiotic susceptibility testing,
      characterization of resistance genes, and molecular typing of pathogens were
      performed. Of 806 urine cultures collected from 626 residents at 44 different
      LTCFs, 492 were positive for microbial infection. Of these, 158 were positive for
      at least an ESBL-producing Enterobacteriaceae species (32.1%), with Escherichia
      coli as the most frequent ESBL pathogen (23.4%) followed by Klebsiella pneumoniae
      (4.5%). Furthermore, 4 carbapenemase producers (0.8%) (1 E. coli with VIM-1and 3
      K. pneumoniae with KPC-3) were detected. The CTX-M-15 type ESBL predominated in
      both E. coli (71.3%) and K. pneumoniae (77.3%). Most E. coli isolates (82.6%)
      belonged to the ST131/H30 clone/subclone. For K. pneumoniae, ST307 and ST15 were
      frequent (31.8% and 22.7%, respectively), but isolates harboring blaKPC-3
      belonged to CC258. Of 136 diarrheic fecal samples collected from 111 residents at
      26 different LTCFs, 21 (15.4%) were positive for toxigenic C. difficile; of
      these, 13 (62%) were MDR (resistant to 3 or more antimicrobial agents of
      different classes). The predominant C. difficile polymerase chain reaction
      ribotype was 356/607 (42.9%), followed by 018, 449, and 078 (14% each). Public
      health efforts are needed to contain the diffusion of CTX-M-producing
      Enterobacteriaceae and MDR C. difficile in LTCF settings.

PMID- 29571839
TI  - Activity of omadacycline tested against Enterobacteriaceae causing urinary tract
      infections from a global surveillance program (2014).
AB  - Omadacycline is an aminomethylcycline with in vitro activity against many gram
      negative pathogens. Omadacycline and comparators were tested against
      Enterobacteriaceae from urinary tract infections (UTIs) selected from a 2014
      global surveillance program and compared to results of isolates from 2010
      surveillance. The omadacycline MIC50/90 for Enterobacteriaceae collected during
      2014 was 2/>=8 MUg/mL (1/4 MUg/mL minus Proteus, Providencia, and Morganella
      spp.). The MIC50/90 for E. coli was 1/2 MUg/mL, similar to that in 2010
      (MIC50/90, 0.5/2 MUg/mL). The MICs for 91.7% of Klebsiella spp. isolates in 2014
      (89.7%, 2010) were <=4 MUg/mL. In 2010 and 2014, a total of 100.0% and 95.8% of
      ESBL screen-positive (SP) phenotype E. coli and 73.9% and 75.0% of ESBL SP
      Klebsiella spp., respectively, exhibited MIC values at <=4 MUg/mL. Omadacycline
      was active against UTI-causing Enterobacteriaceae isolates from NA and EU.
      Further study of omadacycline to treat UTIs caused by Enterobacteriaceae may be
      indicated.

PMID- 29571840
TI  - Dissemination of carbapenem-resistant Klebsiella pneumoniae harboring KPC
      carrying plasmid pKPC_P16, a pKPC_LK30 variant, in northern Taiwan.
AB  - The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) was up to 30%
      between 2014 and 2016 in the study hospital. Of these 77 CRKP isolates, 22
      isolates with sequence type ST11 carried the new pKPC_P16 plasmid, a pKPC_LK30
      variant, and were widely disseminated between 2014 and 2015 in northern Taiwan.

PMID- 29571841
TI  - Proteus mirabilis harboring carbapenemase NDM-5 and ESBL VEB-6 detected in
      Austria.
AB  - We describe a case of carbapenemase-harboring Proteus mirabilis together with
      detection of NDM-5 in Austria accompanied by other bacterial strains with a wide
      range of beta-lactamases including OXA-181 and VEB-6. Isolates were obtained from
      a subphrenic abscess from one patient who was previously treated with broad
      spectrum antibiotics in Bangladesh.

PMID- 29571842
TI  - Comparative effects of low-dose versus standard-dose alteplase in ischemic
      patients with prior stroke and/or diabetes mellitus: The ENCHANTED trial.
AB  - BACKGROUND AND PURPOSE: History of prior stroke (PS) and diabetes mellitus (DM)
      are considered relative contraindications to the use of intravenous alteplase in
      patients with acute ischemic stroke (AIS). We aimed to assess whether a history
      of PS and DM modified the comparative effects of low- versus standard-dose
      alteplase in patients who participated in the alteplase-dose arm of the Enhanced
      Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Data
      from an international, multi-center, prospective, randomized, open-label, blinded
      endpoint trial were used to assess the benefits and risks of low (0.6mg/kg)
      versus standard-dose (0.9mg/kg) intravenous alteplase in thrombolysis-eligible
      AIS patients. Logistic regression was used for analysis of patient subgroups
      defined by history of PS and DM on efficacy and safety outcomes, adjusted for
      confounding variables. RESULTS: After adjusting for baseline characteristics and
      management variables over the first seven days in 3288 AIS patients (431 PS, 489
      DM, and 157 with both), history of PS and DM were not associated with poor
      outcome at 90-days: whether defined by modified Rankin scale (mRS) scores 2-6
      (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.55-1.32; P=0.476) or
      mortality (OR 1.25, 95%CI 0.62-2.52; P=0.533). There was no differential effect
      of low-versus standard-dose alteplase on dichotomized mRS (0-1 vs. 2-6), ordinal
      shift in mRS scores, mortality, or symptomatic intracerebral hemorrhage, by a
      history of PS and DM. CONCLUSIONS: A history of PS and DM was not an independent
      predictor of poor outcome in thrombolysis-treated AIS patients. We were not able
      to demonstrate any effect of these variables in modifying the differences in
      effects of low- versus standard-dose alteplase. CLINICAL TRIAL REGISTRATION:
      http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01422616.

PMID- 29571843
TI  - Identification of a prospective early motor progression cluster of Parkinson's
      disease: Data from the PPMI study.
AB  - AIM: The aim of our study is to phenotype PD motor progression, and to detect
      whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and
      neuropsychological measures characterize PD motor progression phenotypes.
      METHODS: We defined motor progression as a difference of at least one point in
      the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit
      04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers
      Initiative (PPMI) study. H&Y progression events were recorded at each milestone
      in order to be used as cluster analysis variables, in order to produce
      progression phenotypes. Subsequently, cross-cluster comparisons prior to and
      following (pairwise) propensity score matching were performed in order to assess
      phenotype - defining characteristics. RESULTS: Four progression clusters where
      identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and
      V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non
      Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal
      H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann
      Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and
      Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as
      statistically significant cross-cluster characteristics. Following Propensity
      Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1,
      CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line
      Orientation Test (BJLOT) were determined as statistically significant predictors
      of cluster differentiation (p < 0.05). DISCUSSION: SFT, Serum IGF1, CSF aSyn and
      DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further
      investigation as possible motor progression biomarkers.

PMID- 29571844
TI  - Cerebral infarction due to Zika virus.

PMID- 29571845
TI  - Imaging intralesional heterogeneity of sodium concentration in multiple
      sclerosis: Initial evidence from 23Na-MRI.
AB  - Sodium MRI (23Na-MRI) has been used to non-invasively quantify tissue sodium but
      has been limited by low spatial resolution. Here we demonstrate for the first
      time that high resolution 23Na-MRI reveals the spatial heterogeneity of sodium
      concentration within a multiple sclerosis (MS) lesion. A patient with treatment
      naive relapsing-remitting MS and a ring-enhancing lesion was imaged using 23Na
      MRI. The periphery of the lesion demonstrated an elevated total sodium content
      compared to the normal appearing white and grey matter (p<0.01), as well as a
      heterogeneous distribution of both the total tissue sodium concentration and the
      intracellular-weighted sodium concentration.

PMID- 29571846
TI  - Neutrophil to lymphocyte ratio and early clinical outcomes in patients with acute
      ischemic stroke.
AB  - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is closely linked to
      mortality in patients with cardiovascular disease. We investigated whether NLR is
      associated with early clinical outcomes in patients with acute ischemic stroke.
      METHODS: We collated data from a tertiary hospital's stroke registry including
      admitted patients with a first-ever acute ischemic stroke within 72 h of onset.
      White blood cell counts and peripheral differential counts were measured on
      admission. Early clinical outcomes were in-hospital mortality and disability at
      discharge assessed by the modified Rankin scale (mRS). RESULTS: Among 1131 stroke
      patients, 454 patients were included and classified into tertile groups based on
      NLR on admission. Patients in higher tertiles of NLR were likely to have severe
      neurologic deficit at discharge. Higher NLR tertiles were associated with an
      unfavourable shift of mRS score (p < .0001). This association remained
      significant after adjustment for clinical and laboratory variables including age,
      sex, hypertension, hypercholesterolemia, atrial fibrillation, stroke severity,
      and glucose level (p = .032 for trend). However, risk of death or major
      disability (score of 3-6 on mRS) and in-hospital mortality were not significantly
      different across NLR tertile groups. CONCLUSIONS: In patients with acute ischemic
      stroke, NLR was predictive of short-term functional outcome.

PMID- 29571847
TI  - Study of the placentae of patients with neuromyelitis optica spectrum disorder.
AB  - Previous studies have shown that circulating AQP4-IgG may lead to negative
      consequences during pregnancy in patients with neuromyelitis optica spectrum
      disorder (NMOSD). The objective of this study was to explore whether AQP4-IgG
      influences pregnancy by affecting AQP4 expression and inducing placental
      inflammation in patients with NMOSD. We prospectively collected clinical data
      from six pregnant AQP4-IgG-seropositive NMOSD patients and their infants, and
      investigated AQP4 expression and placental inflammatory infiltration by comparing
      hematoxylin and eosin and immunohistochemical (AQP1, AQP4, C5b-9, IgG, CD3, CD8,
      CD20, and CD68) staining results with three normal controls. Four patients were
      term pregnant and their infants were normal for development, serum AQP4-IgG was
      positive at the time of birth, and three infants were negative for AQP4-IgG after
      3 months. Two patients underwent induced abortion; one because of NMOSD relapse
      and another because of fetal malformation. Histological investigation showed
      normal structure of the chorionic villi, and no significant difference in the
      intensity of the immunohistochemical staining for AQP1, AQP4, and inflammatory
      markers in placentae of patients and the controls. Our results showed that there
      was no significant decrease in placental AQP4 expression, and no obvious
      placental inflammation or signs of damage in term placentae of NMOSD patients
      seropositive for AQP4-IgG.

PMID- 29571848
TI  - Ischemic stroke due to embolic heart diseases and associated factors in Benin
      hospital setting.
AB  - INTRODUCTION: Poor access to cardiovascular checkups is a major cause of
      ignorance of embolic heart diseases as the etiology for ischemic stroke.
      OBJECTIVE: Study ischemic strokes due to embolic heart diseases and their
      associated factors. METHOD: It was a cross-sectional, prospective, descriptive
      and analytical study conducted from November 1, 2014 to August 31, 2015 on 104
      patients with ischemic stroke confirmed through brain imaging. Embolic heart
      diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter,
      myocardial infarction (MI), heart valve diseases and atrial septal aneurysm
      (ASA). The dependent variable was embolic heart disease while independent
      variables encompassed socio-demographic factors, patients' history, and
      lifestyle. Data analysis was carried out through SAS 9.3. RESULTS: The rate of
      embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF
      accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic
      stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for
      heart valve diseases, MI and ASA. The associated factor was age (p=0.000).
      CONCLUSION: The diagnosis of a potential cardiac source of embolism is essential
      because of therapeutic and prognostic implications. Wherefore, there is need for
      cardiovascular examination particularly Holter ECG and cardiac ultrasound
      examination which are not always accessible to our populations.

PMID- 29571849
TI  - Oligoclonal bands and periventricular lesions in multiple sclerosis will not
      increase blood-brain barrier permeability.
AB  - OBJECTIVE: To elucidate the etiology and clinical significance of periventricular
      lesions (PVLs) and oligoclonal bands (OB) in multiple sclerosis (MS). METHODS: We
      enrolled a total of 97 MS patients (67 OB-positive and 30 OB-negative) who were
      negative both for anti-aquaporin-4 (AQP4) autoantibody and anti-myelin
      oligodendrocyte glycoprotein (MOG) antibody. In these patients, comprehensive
      data including clinical, laboratory, and MRI were collected to investigate the
      significance of OB and PVLs. RESULTS: Within the MS patients, OB-positivity and
      the number of PVLs were associated each other. Both of OB-positivity and PVLs did
      not affect clinical severity or relapse rate, though the patients with >=3 PVLs
      showed faster cerebral atrophy than those with <3 PVLs. The patients with OB or
      >=3 PVLs showed lower values of quotient of albumin (QAlb), a biomarker of blood
      brain barrier (BBB)-permeability and possibly reflects the ongoing disease
      activity, and lower protein levels in cerebrospinal fluid (CSF). The causal
      relationship between the decreased QAlb and OB or >=3 PVLs was not determined.
      CONCLUSIONS: OB and PVLs were associated each other, but they did not affect the
      clinical course or increased the BBB-permeability within MS patients.

PMID- 29571850
TI  - Phenotypical features of two patients diagnosed with PHARC syndrome and carriers
      of a new homozygous mutation in the ABHD12 gene.
AB  - PHARC (Polyneuropathy, Hearing loss, Ataxia, Retinitis pigmentosa and Cataracts)
      (MIM# 612674) is an autosomal recessive neurodegenerative disease caused by
      mutations in the ABHD12 gene. We evaluated two Spanish siblings affected with pes
      cavus, sensorimotor neuropathy, hearing loss, retinitis pigmentosa and juvenile
      cataracts in whom the genetic test of ABHD12 revealed a novel homozygous
      frameshift mutation, c.211_223del (p.Arg71Tyrfs*26). The earliest clinical
      manifestation in these patients was a demyelinating neuropathy manifested with a
      Charcot-Marie-Tooth phenotype over three decades. Progressive hearing loss,
      cataracts and retinitis pigmentosa appeared after the age of 30. We herein
      describe the complete clinical picture of these two patients, and focus
      particularly on neuropathy characteristics. This study supports the fact that
      although PHARC is rare, its phenotype is very characteristic and we should
      include its study in patients affected with demyelinating polyneuropathy, hearing
      loss and retinopathy.

PMID- 29571851
TI  - In a stroke cohort with incident hypertension; are more women than men likely to
      be excluded from recombinant tissue-type Plasminogen Activator (rtPA)?
AB  - BACKGROUND: The treatment outcomes in the use of rt-PA have been reported. Some
      studies reported worse outcome in women than men, while others presented opposing
      data. Using data from a hospital-based stroke registry, we investigated evidence
      of gender difference and determined exclusion criteria in a stroke population
      with incidence of hypertension. METHOD: In a stroke population of women and men
      with incident of hypertension from a stroke registry, demographics and clinical
      factors were compared. Univariate analysis was used to determine gender
      differences, while multivariable models adjusted for demographic and clinical
      variables. RESULTS: Among the 669 stroke patients with incident of hypertension
      that were excluded from rt-PA treatment, 362 were female and 307 were male.
      Female patients with increasing age (OR = 0.956-0.984, P < 0.001), diabetes
      mellitus (OR = 0.095-0.559, P = 0.001), higher NIH stroke scale score (OR = 1.019
      1.090, P = 0.002), previous stroke (OR = 0.337-0.850, P = 0.008), diabetes
      medication (OR = 1.200-7.724, P = 0.019), and INR (OR = 0.033-0.597, P = 0.008)
      are more likely to be excluded. Male patients with a history of a previous stroke
      (OR = 0.265-0.704, P = 0.001), risk of mortality (OR = 0.803-0.950, P = 0.002),
      higher NIH stroke scale score(OR = 1.101-1.276, P < 0.001), cholesterol reducing
      medication (OR = 1.191-2.910, P = 0.006), weakness at presentation(OR = 1.207
      4.421, P = 0.011), and INR (OR = 0.016-0.243, P < 0.001) are more likely to be
      excluded. CONCLUSION: Women have a worse outcome than men in an untreated acute
      ischemic stroke population, but when treated, women have a better treatment
      outcome compared to men. In a hypertensive stroke population, the clinical
      variables for the exclusion criteria for women and men are significantly
      different, even after adjustment for confounding variables.

PMID- 29571852
TI  - MRI scout images can detect the acute intracerebral hemorrhage on CT.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) has recently emerged as a first
      line tool for investigating acute stroke. However, MRI requires long scan times,
      which could be detrimental for severe stroke patients with a large intracerebral
      hemorrhage (ICH). MRI scout images, which are taken prior to a study to determine
      the range of subsequent images, can be used to rapidly screen the whole brain. We
      examined whether MRI scout imaging can detect ICHs observed by computed
      tomography (CT). METHODS: Between September 2014 and March 2016, consecutive
      acute ICH patients who underwent both MRI scout and CT imaging in the acute
      setting were studied. ICHs on MRI scout images were defined as space-occupying
      lesions. Two neurologists independently assessed the scout images. We
      investigated whether ICHs on CT scans can be detected on MRI scout images and the
      characteristics of ICHs not detected by MRI scout images. RESULTS: One hundred
      and forty-eight ICH patients (median age, 68 [interquartile range, 59-77] years;
      99 [67%] males; median National Institutes of Health Stroke Scale score, 11 [4
      17]) were enrolled. Among these, 138 (93%) patients were diagnosed as having ICH
      by MRI scout imaging (positive group), and 10 (7%) patients were not (negative
      group). The bleeding volume was 9.3 [4.5-22.4] ml in the positive group and 1.0
      [0.4-2.0] ml in the negative group (p < .001). The cut-off value of bleeding
      volume calculated from the receiver operating characteristic curve was 2.0 ml.
      Regarding ICH lesions, 4 (44%) of the 9 pontine hemorrhages were detected on MRI
      scout images, whereas 134 (96%) of the 139 other hemorrhages were diagnosed (p <
      .001). CONCLUSIONS: We diagnosed >90% of ICHs using MRI scout images. Low levels
      of ICH and pontine hemorrhaging might be difficult to detect using MRI scout
      imaging.

PMID- 29571853
TI  - Bilateral apraxia of eyelid closure following bilateral subcortical frontal
      infarcts.

PMID- 29571854
TI  - Effect of switching from glatiramer acetate 20 mg/daily to glatiramer acetate 40
      mg three times a week on gray and white matter pathology in subjects with
      relapsing multiple sclerosis: A longitudinal DTI study.
AB  - BACKGROUND: Glatiramer acetate (GA) 40 mg * 3/weekly was approved for the
      treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial
      effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been
      demonstrated, the effect of GA 40 mg * 3/weekly at the microstructural tissue
      level has yet to be explored. OBJECTIVE: To investigate the effect of switching
      from GA 20 mg/daily to GA 40 mg * 3/weekly on the evolution of microstructural
      changes in the thalamus and normal appearing white matter (NAWM), using diffusion
      tensor imaging (DTI). METHODS: In this observational, longitudinal, cross-over,
      34-month MRI study, we recruited 150 RRMS patients that underwent MRI 12-18
      months before switching (pre-index), during the switch (index) and 12-18 months
      after switching (post-index) from GA 20 mg/daily to GA 40 mg * 3/weekly. Regional
      DTI metrics and tract-based spatial statistics (TBSS) analyses were performed.
      Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and
      fractional anisotropy (FA) were measured in thalamus and NAWM. RESULTS: Regional
      DTI measures, measures of whole brain, white and gray matter, and thalamus
      volumes, as well as lesion volume, showed no significant changes. However, the
      voxel-wise TBSS analysis showed increased FA both in the NAWM and thalamus, as
      well as increased MD and AD in NAWM, and decreased RD in NAWM (p < .05). Areas of
      increased FA and MD as well as decreased RD in the NAWM, and increased AD both in
      the NAWM and thalamus were detected between index to post-index (p < .05).
      CONCLUSIONS: This study confirms a comparable effect of GA 40 mg * 3/weekly to GA
      20 mg/daily on DTI measures over 34 months.

PMID- 29571855
TI  - Quantification of whole-body bradykinesia in Parkinson's disease participants
      using multiple inertial sensors.
AB  - Bradykinesia (slowness of movement) is a common motor symptom of Parkinson's
      disease (PD) that can severely affect quality of life for those living with the
      disease. Assessment and treatment of PD motor symptoms largely depends on
      clinical scales such as the Unified Parkinson's Disease Rating Scale (UPDRS).
      However, such clinical scales rely on the visual assessment by a human observer,
      naturally resulting in inter-rater variability. Although previous studies have
      developed objective means for measuring bradykinesia in PD patients, their
      evaluation was restricted by the type of movement and number of joints assessed.
      These studies failed to provide a more comprehensive, whole-body evaluation
      capable of measuring multiple joints simultaneously. This study utilizes wearable
      inertial measurement units (IMUs) to quantify whole-body movements, providing
      novel bradykinesia indices for walking (WBI) and standing up from a chair (sit-to
      stand; SBI). The proposed bradykinesia indices include the joint angles at both
      upper and lower limbs and trunk motion to compute a complete, objective score for
      whole body bradykinesia. Thirty PD and 11 age-matched healthy control
      participants were recruited for the study. The participants performed two
      standard walking tasks that involved multiple body joints in the upper and lower
      limbs. The WBI and SBI successfully identified differences between control and PD
      participants. The indices also effectively identified differences within the PD
      population, distinguishing participants assessed with (ON) and without (OFF)
      levodopa; the gold-standard of treatment for PD. The goal of this study is to
      provide health professionals with an objective score for whole body bradykinesia
      by simultaneously measuring the upper and lower extremities along with truncal
      movement. This method demonstrates potential to be used in conjunction with
      current clinical standards for motor symptom assessment, and may also be
      promising for the remote assessment of PD patients and in cases where experienced
      clinicians may not be available. In conclusion, the intelligent use of this
      technology for the measurement of bradykinesia (among other symptoms) has vast
      implications for optimizing treatment in Parkinson's disease, ultimately leading
      to an improvement in quality of life.

PMID- 29571856
TI  - Software updates of OCT segmentation algorithms influence longitudinal assessment
      of retinal atrophy.
AB  - OBJECTIVE: To investigate whether there is a systematic difference in
      peripapillary retinal nerve fiber layer (pRNFL) thickness measurements between
      subsequent updates of pRNFL segmentation software provided by Heidelberg
      Spectralis optical coherence tomography (OCT). METHODS: In total, 838 pRNFL scans
      from 213 multiple sclerosis (MS) patients and 61 healthy controls were analyzed.
      All scans were performed on the same OCT device followed by automated
      segmentation (HRA 5.6.4.0) and data extraction. Subsequently, all scans were re
      segmented with an updated software version (HRA 6.0.7.0). To assess level of
      agreement between the two algorithms, Bland-Altman Plots were constructed. Paired
      samples t-test and linear regression analyses were used to investigate for
      differences in mean thickness and proportional bias respectively. RESULTS:
      Overall, the updated version showed an overestimation of 0.16MUm [95%CI 0.097
      0.23, p<0.001] for the global pRNFL thickness compared to the earlier version.
      The largest differences were found for the nasal inferior (mean ? 0.29MUm,
      p<0.001) and temporal inferior (mean ? 0.43MUm, p<0.001) sectors. Inspection of
      the Bland-Altman Plot revealed that the difference between the two versions could
      be up to 6MUm for the global mean. There was no proportional bias for the global
      mean (beta=0.003, p=0.245) nor for any of the separate sectors. CONCLUSION: The
      data show a significant difference in pRNFL thickness measurements between two
      subsequent versions of the same segmentation software. Although the mean
      difference was relatively small, the differences within the individual subject
      could be considerably higher than the known atrophy rate of 1MUm/year in MS.

PMID- 29571857
TI  - A novel presenilin 1 mutation (Leu418Trp) associated with spasticity,
      parkinsonism, and white matter lesion in a dominant Alzheimer's family.

PMID- 29571858
TI  - Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with optic
      neuritis and seizures.
AB  - We describe four patients who experienced optic neuritis (ON) and seizures and
      were found to have antibodies to myelin oligodendrocyte glycoprotein (MOG) in
      serum. The index case was a previously healthy 39-year-old man who developed
      steroid dependent ON and had a generalized seizure when steroids were tapered. He
      tested positive for antibodies to MOG. We have reviewed the charts of all 11 anti
      MOG antibody positive patients in our practice and found that 4 patients, all of
      whom had experienced one or more episodes of ON, also had a generalized seizure
      during the course of their illness. In 2 patients - including the index case -
      seizure occurred during steroid taper and in 2 others at the time of an episode
      of acute disseminated encephalomyelitis (ADEM). Association of anti-MOG
      antibodies and relapsing demyelinating disorders of the central nervous system is
      increasingly recognized. Testing for anti-MOG antibodies should be considered in
      patients with optic neuritis and seizures, especially in those with who also have
      a history of ADEM.

PMID- 29571859
TI  - Plasma citrulline levels are increased in patients with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disorder of the
      central nervous system (CNS). Myelin basic protein (MBP), which is one of the
      main compounds of CNS myelin, appears to be hypercitrullinated in the brain of
      patients with MS. We hypothesized that MS is associated with an increased release
      of citrulline from the brain. METHODS: Twenty-five patients with MS, 25 controls
      without neurological disease (CwND) and 25 subjects with non-MS cerebral white
      matter lesions were included in this study. Groups were matched for age and
      gender. Clinical MS disability measures were recorded by means of Expanded
      Disability Status Scale (EDSS) scores and Multiple Sclerosis Severity Scores
      (MSSS). Citrulline was assessed in plasma obtained from an antecubital peripheral
      vein (PV) in all participants. Additional internal jugular vein (IJV) samples
      were examined in 10 patients with MS and 10 CwND. Twelve patients with MS
      underwent brain magnetic resonance imaging to determine total brain and T2 fluid
      attenuated inversion recovery lesion volume. RESULTS: Median [IQR] PV citrulline
      levels were increased in patients with MS (50.47 [86.61] MUM), as compared to
      CwND (33.58 [43.65] MUM, P = 0.042) and subjects with non-MS cerebral white
      matter lesions (32.41 [28.86] MUM, P = 0.006). Citrulline IJV levels and IJV/PV
      ratios were comparable between patients with MS and CwND. No significant
      correlations were found between PV citrulline levels and any of the clinical, nor
      radiological, disease measures. CONCLUSION: PV plasma levels of citrulline are
      elevated in patients with MS but this does not seem to result from an augmented
      release from the brain. Increased plasma citrulline may be a promising new
      biomarker in MS but the origin and significance need to be further elucidated.

PMID- 29571860
TI  - Is the impact of fatigue related to walking capacity and perceived ability in
      persons with multiple sclerosis? A multicenter study.
AB  - BACKGROUND: The relationship between fatigue impact and walking capacity and
      perceived ability in patients with multiple sclerosis (MS) is inconclusive in the
      existing literature. A better understanding might guide new treatment avenues for
      fatigue and/or walking capacity in patients with MS. OBJECTIVE: To investigate
      the relationship between the subjective impact of fatigue and objective walking
      capacity as well as subjective walking ability in MS patients. METHODS: A cross
      sectional multicenter study design was applied. Ambulatory MS patients (n = 189,
      age: 47.6 +/- 10.5 years; gender: 115/74 women/men; Expanded Disability Status
      Scale (EDSS): 4.1 +/- 1.8 [range: 0-6.5]) were tested at 11 sites. Objective
      tests of walking capacity included short walking tests (Timed 25-Foot Walk
      (T25FW), 10-Metre Walk Test (10mWT) at usual and fastest speed and the timed up
      and go (TUG)), and long walking tests (2- and 6-Minute Walk Tests (MWT).
      Subjective walking ability was tested applying the Multiple Sclerosis Walking
      Scale-12 (MSWS-12). Fatigue impact was measured by the self-reported modified
      fatigue impact scale (MFIS) consisting of a total score (MFIStotal) and three
      subscales (MFISphysical, MFIScognitive and MFISpsychosocial). Uni- and
      multivariate regression analysis were performed to evaluate the relation between
      walking and fatigue impact. RESULTS: MFIStotal was negatively related with long
      (6MWT, r = -0.14, p = 0.05) and short composite (TUG, r = -0.22, p = 0.003)
      walking measures. MFISphysical showed a significant albeit weak relationship to
      walking speed in all walking capacity tests (r = -0.22 to -0.33, p < .0001),
      which persisted in the multivariate linear regression analysis. Subjective
      walking ability (MSWS-12) was related to MFIStotal (r = 0.49, p < 0.0001), as
      well as to all other subscales of MFIS (r = 0.24-0.63, p < 0.001), showing
      stronger relationships than objective measures of walking. CONCLUSIONS: The
      physical impact of fatigue is weakly related to objective walking capacity, while
      general, physical, cognitive and psychosocial fatigue impact are weakly to
      moderately related to subjective walking ability, when analysed in a large
      heterogeneous sample of MS patients.

PMID- 29571861
TI  - A diagnostic decision tree for adult cerebellar ataxia based on pontine magnetic
      resonance imaging.
AB  - Cerebellar ataxias (CAs) are heterogeneous conditions often require differential
      diagnosis. This study aimed to establish a diagnostic decision tree for
      differentiating CAs based on pontine MRI findings. Two-hundred and two
      consecutive ataxia patients were clinically classified into 4 groups: (1)
      spinocerebellar ataxia (SCA) with brainstem involvement (SCA-BSI), (2) Pure
      cerebellar SCA, (3) cerebellar dominant multiple system atrophy (MSA-c), and (4)
      Other CA. Signal intensity in pons was graded into 3 types: hot cross bun sign
      (HCBS), pontine midline linear T2-hyperintensity (PMH), or normal. The distance
      ratio of pontine base to tegmentum, named "BT-ratio", was measured. The presence
      of HCBS indicated either MSA-c with a specificity of 97.7%, or SCA2. When PMH was
      observed, a BT-ratio above 3.54 strongly indicated SCA-BSI, namely Machado-Joseph
      disease, SCA1, or dentatorubral-pallidoluysian atrophy, whereas a BT-ratio below
      3.54 indicated MSA-c or SCA2. When the signal intensity was normal, a BT-ratio
      above 3.52 indicated SCA-BSI, whereas a BT-ratio below 3.52 suggested Pure
      cerebellar SCA or Other CA with pure cerebellar type. The decision tree was
      confirmed useful in a different 30 CA patients. We propose that differential
      diagnosis of CAs can be supported by combining pontine MRI signal intensity
      changes and BT-ratio.

PMID- 29571862
TI  - Emergent carotid artery stenting in atherosclerotic disease of the internal
      carotid artery with tandem intracranial occlusion.
AB  - BACKGROUND: Several randomized clinical trials have proven the safety and
      efficacy of mechanical thrombectomy (MT) in large vessel occlusions; nonetheless,
      there is still no consensus concerning hyperacute management of tandem
      occlusions. Recent studies have suggested that emergent carotid artery stenting
      (eCAS), along with mechanical thrombectomy, is an effective and safe treatment
      option. AIMS: To characterize the safety and short-term outcome of patients
      treated with eCAS during endovascular treatment of acute ischaemic stroke.
      METHODS: Review of the prospective patient registry submitted to MT for anterior
      circulation acute ischaemic stroke in a single referral centre and selection of
      patients treated with eCAS for atherosclerotic occlusion or near-occlusion of
      cervical internal carotid artery during 22 consecutive months. Clinical data was
      collected, and assessment of procedure safety and 3-month-outcome were performed.
      RESULTS: Among 156 patients submitted to MT, 16 patients (10.3%) underwent eCAS.
      Most patients were male (15/16), median age was 64.5 years (interquartile range
      [IQR] = 57-75), median admission NIHSS was 14 (IQR = 11.5-19) and 10/16 patients
      had been submitted to intravenous thrombolysis. Successful recanalization was
      obtained in 93.8% of the patients. One patient (6.3%) experienced symptomatic
      intracranial haemorrhage, one patient experienced early intra-stent thrombosis
      and one patient developed cerebral hyperperfusion syndrome. At 3-month follow-up,
      11 patients were independent (68.8%) and 1 patient had died (6.3%). CONCLUSIONS:
      In this study, positive results were obtained using eCAS. Although an optimal
      intervention for this type of occlusions has not yet been formally established,
      eCAS has been surging has a feasible and safe treatment option.

PMID- 29571864
TI  - Radiation-induced meningiomas: A case-control study at single center institution.
AB  - BACKGROUND: Our understanding of radiation induced meningiomas (RIM) is limited.
      It has been suggested that RIM harbor more aggressive cellular pathology and must
      be observed vigilantly. However, the actual recurrence rates of RIM compared to
      the sporadic meningiomas has yet to be defined. OBJECTIVE: We employ a single
      center case-control study to retrospectively assess recurrence rates between RIM
      (n = 12) and sporadic meningiomas (n = 118). METHODS: The criteria for the RIM
      group included the following: 1) History of intracranial clinical-dose radiation
      2) Initial pathology other than meningioma, 3) Radiation administered greater
      than 5 years prior to meningioma onset. Recurrence rates, extent of resection and
      outcomes were analyzed. RESULTS: There was a significant difference in recurrence
      rates between the RIM group and sporadic meningioma: 50% vs. 5% respectively, p =
      0.004. There was no significant difference in race, preoperative tumor volume,
      extent of resection, Ki67, or age between the two groups. Multivariate analysis
      demonstrated that size (OR 0.95 95%CI (0.92-0.99)), extent of resection (OR 1.08
      95%CI (1.01-1.14)), WHO grade (OR 160.24 95% CI (6.32-74509)) and history of
      previous radiation (OR 1.28 95%CI (1.01-1.62)) were independent risk factors for
      recurrence. RIM patients had significantly higher proportion of atypical or
      malignant histology compared to sporadic patients (p < 0.0001). CONCLUSION: RIM
      patients may have a higher predisposition for tumor recurrence than patients with
      sporadic RIM. The use of Ki67 indices may help identify patients with a higher
      risk of tumor recurrence. Prospective studies focusing on newly diagnosed
      patients with RIM may help identify an optimal surveillance and treatment plan.

PMID- 29571863
TI  - The new Mobile Universal Lexicon Evaluation System (MULES): A test of rapid
      picture naming for concussion sized for the sidelines.
AB  - OBJECTIVE: Measures of rapid automatized naming (RAN) have been used for over 50
      years to capture vision-based aspects of cognition. The Mobile Universal Lexicon
      Evaluation System (MULES) is a test of rapid picture naming under investigation
      for detection of concussion and other neurological disorders. MULES was designed
      as a series of 54 grouped color photographs (fruits, random objects, animals)
      that integrates saccades, color perception and contextual object identification.
      Recent changes to the MULES test have been made to improve ease of use on the
      athletic sidelines. Originally an 11 * 17-inch single-sided paper, the test has
      been reduced to a laminated 8.5 * 11-inch double-sided version. We identified
      performance changes associated with transition to the new, MULES, now sized for
      the sidelines, and examined MULES on the sideline for sports-related concussion.
      METHODS: We administered the new laminated MULES to a group of adult office
      volunteers as well as youth and collegiate athletes during pre-season baseline
      testing. Athletes with concussion underwent sideline testing after injury. Time
      scores for the new laminated MULES were compared to those for the larger version
      (big MULES). RESULTS: Among 501 athletes and office volunteers (age 16 +/- 7
      years, range 6-59, 29% female), average test times at baseline were 44.4 +/- 14.4
      s for the new laminated MULES (n = 196) and 46.5 +/- 16.3 s for big MULES (n =
      248). Both versions were completed by 57 participants, with excellent agreement
      (p < 0.001, linear regression, accounting for age). Age was a predictor of test
      times for both MULES versions, with longer times noted for younger participants
      (p < 0.001). Among 6 athletes with concussion thus far during the fall sports
      season (median age 15 years, range 11-21) all showed worsening of MULES scores
      from pre-season baseline (median 4.0 s, range 2.1-16.4). CONCLUSION: The MULES
      test has been converted to an 11 * 8.5-inch laminated version, with excellent
      agreement between versions across age groups. Feasibly administered at pre-season
      and in an office setting, the MULES test shows preliminary evidence of capacity
      to identify athletes with sports-related concussion.

PMID- 29571865
TI  - Preoperative biomarkers in patients with idiopathic normal pressure hydrocephalus
      showing a favorable shunt surgery outcome.
AB  - INTRODUCTION: Idiopathic normal pressure hydrocephalus (INPH) is known to be a
      potentially treatable neurologic condition. The neurocognitive outcomes after
      surgery, however, have been variable. It is important to define preoperative
      characteristics of patients that predicts the shunting outcome. We aimed to
      compare baseline differences between shunt-responsive and unresponsive patients
      after 1year from surgery in order to identify preoperative predictors showing
      favorable clinical outcomes. METHODS: Among 69 candidates, 31 patients with
      probable INPH completed the study. Patients were divided into two groups,
      responsive group (n=17) and unresponsive group (n=14), according to the clinical
      outcomes on INPH grading scale and modified Rankin score (MRS). Preoperative
      cerebrospinal (CSF) Abeta, tau levels, MRI findings, and clinical characteristics
      were compared between the groups. Correlations between shunt responsiveness and
      preoperative characteristics were also assessed. RESULTS: After 1year from shunt,
      gait problem was the most likely to improve. Shunt-responsive group showed lower
      CSF p-tau/Abeta, fewer lacunes, and higher incidence of disproportionately
      enlarged subarachnoid space (DESH) signs on MRIs compared to those in
      unresponsive group. Favorable outcome was related with positive DESH sign and
      fewer lacunes. CONCLUSIONS: Our results suggest that biomarkers representing non
      INPH related pathology including Alzheimer's disease and small vessel disease
      might show less favorable clinical outcomes after 1year from surgery.

PMID- 29571866
TI  - DAPK1-ERK signal mediates oxygen glucose deprivation reperfusion induced
      apoptosis in mouse N2a cells.
AB  - AIMS: Death-associated protein kinase 1 (DAPK1) is a kinase found to promote
      neuronal apoptosis induced by ischemia. Extracellular signal-regulated kinase
      (ERK) was identified as a key molecule in DAPK1 signaling. However, the
      mechanisms of neuronal ischemia reperfusion injury remain unknown. Here, we
      investigate the influence of DAPK1-ERK signal on neuronal apoptosis following
      ischemia reperfusion. METHODS: Mouse N2a cells were used in this study and
      primary cultured neurons along with mice were adopted as supplements. Oxygen
      glucose deprivation (OGD) or administration of N-methyl-d-aspartate (NMDA) and
      glycine was performed on cells while middle cerebral artery occlusion (MCAO)
      model on mice. DAPK1 knocking down was achieved by lentiviral-delivered shRNA.
      Protein expressions were evaluated by western blots. Protein-protein binding was
      confirmed by co-immunoprecipitation and immunofluorescent assay. Apoptosis of
      cells was measured by flow cytometry and lacate dehydrogenase (LDH) leakage
      assay. RESULTS: Ischemia reperfusion resulted in increased DAPK1 and ERK
      activation as well as aggravated apoptosis in a time-dependent manner. DAPK1 was
      proved to bind to ERK during reperfusion following OGD, MCAO and excitotoxicity
      model. Interception of this binding by knocking down DAPK1 led to nuclear
      translocation of ERK and reduced apoptosis. CONCLUSION: Our study revealed the
      DAPK1-ERK signal as a potential mechanism contributing to neuronal apoptosis in
      response to ischemia reperfusion. Disruption of this signal pathway could be a
      promising therapeutic target against stroke.

PMID- 29571867
TI  - Excessive daytime sleepiness may be associated with caudate denervation in
      Parkinson disease.
AB  - Excessive daytime sleepiness (EDS) is one of the earliest and most common non
      motor symptoms of PD, substantially impacting on patient's quality of life. Using
      the Parkinson's Progression Markers Initiative database, we performed a case
      control study to investigate whether dopaminergic deficit is associated with the
      development of EDS using dopaminergic specific single photon emission computed
      tomography (SPECT) molecular imaging of dopamine transporters (DAT). We enrolled
      84 early de novo PD patients with EDS and 84 without EDS, who were matched for
      age, gender, age of diagnosis, years of education and disease duration. We
      assessed and compared semi-quantified [123I]FP-CIT SPECT, and motor and non-motor
      features among these two groups, alongside exploring the clinical and imaging
      correlates of EDS and the predictive significance of these markers in the
      development of EDS. PD patients with EDS had worse non-motor (MDS-UPDRS Part-I, P
      < 0.001) and motor (MDS-UPRDS Part-II, P = 0.005) experiences of daily living, as
      well as worse autonomic (SCOPA-AUT, P < 0.0001) and cognitive (MoCA P = 0.05)
      function, depression (GDS, P = 0.002), and reduced caudate DAT ([123I]FP-CIT, P =
      0.024) compared to PD patients without EDS. Lower caudate [123I]FP-CIT values
      correlated with higher EDS scores (r = -0.192, P = 0.013). Among patients without
      EDS, 47 PD patients (56%) developed EDS over a median follow-up of 36 months. Cox
      multivariate analysis, including all clinical and imaging data available,
      revealed that abnormal caudate [123I]FP-CIT uptake (P = 0.030) and disease
      duration (P = 0.018) were predictors for the development of EDS. Although our
      findings indicate that dopaminergic deficits in the caudate may be associated to
      EDS in patients with PD, the pathophysiological causality is debateable, given
      that dopamine caudate denervation may covary with dopaminergic involvement at
      other targets and with non-dopaminergic involvement.

PMID- 29571868
TI  - Neuromuscular diseases associated with Human Immunodeficiency Virus infection.
AB  - From the most common distal symmetric polyneuropathy (Bilgrami and O'Keefe, 2014)
      to the rare motor neuron diseases, HIV infection is associated with pathology at
      all levels of the peripheral nervous system. HIV infection can cause these
      conditions due to viral exposure itself, the resulting immune dysregulation,
      opportunistic infections found in untreated patients, and from the therapy used
      in treatment of the virus. Before the advent of antiretroviral therapy, 5
      neuromuscular diseases associated with HIV often resulted from opportunistic
      infections. With advances in antiretroviral therapy, the etiologies of
      neuromuscular complications more frequently become the result of prolonged HIV
      exposure, comorbid diseases, and side effects of medications. In this article we
      review the literature on HIV associated neuromuscular diseases, emphasizing the
      more recent studies in the post antiretroviral era, but also reviewing conditions
      more prevalent in the pre antiretroviral era which continue to be seen in
      developing countries and resource poor areas. This discussion includes the
      following conditions: distal symmetric polyneuropathy, autonomic neuropathy,
      inflammatory demyelinating polyneuropathy, mononeuropathy, mononeuropathy
      multiplex, polyradiculopathies, myelopathy, myopathy, motor neuron disease, and
      antiretroviral treatment related conditions.

PMID- 29571869
TI  - Prevalence of functional (psychogenic) parkinsonism in two Swiss movement
      disorders clinics and review of the literature.
AB  - BACKGROUND: Functional parkinsonism (FP) is considered rare but no studies have
      looked at its frequency. Case series have described high rates of comorbidity
      with Parkinson's disease (PD), suggesting a possible association between these
      conditions. OBJECTIVES: To study the prevalence, epidemiology and clinical
      features of FP and its association with PD. METHODS: We conducted a cross
      sectional population-based prevalence study as well as a chart review of cases
      who received a diagnosis of FP over a 10-year-period in two movement disorder
      clinics in Switzerland. Epidemiological data regarding FP features were
      collected. The co-occurrence of PD, psychiatric disorders and other functional
      disorders were recorded. Clinical differences between FP and FP+PD groups are
      presented and discussed in light of a literature review. RESULTS: The crude
      prevalence of FP was 0.64 per 100,000 in our population. FP represented 0.24% of
      patients with parkinsonism. Among 12 FP cases, female gender predominance (87%),
      mean age of onset of 45.5(+/-13.3 Standard deviation SD) years and prolonged
      diagnostic delay (mean 59+/-75 SD months) was found. Six patients had an
      additional diagnosis of PD, 83% of depression and 66% of other functional
      neurological disorder. In four patients with FP+PD, FP preceded PD by 6 to
      56months. CONCLUSIONS: These results suggest that FP should be considered in the
      differential diagnosis of patients presenting with parkinsonism. The high rate of
      co-occurrence with PD emphasizes the importance of long-term follow up of these
      patients. The observation that FP often precedes PD should be verified in
      prospective studies.

PMID- 29571870
TI  - Characteristics of the ischemic stroke patients whose seizures occur at stroke
      presentation at a single institution in Eastern China.
AB  - PURPOSE: We compared clinical characteristics and outcomes of the early-onset
      seizure post-stroke patients who had seizures occurring at stroke presentation
      (SSP) with other patients without SSP at a single institution in Eastern China.
      METHODS: We reviewed 20,947 ischemic stroke patients in our hospital electronic
      medical records system from January 2007 to December 2016. Among them, there were
      91 (0.43%) patients with early-onset seizure post-stroke. Among these 91
      patients, there were 35 (0.16%) SSP patients and another 56 (0.27%) were
      designated as non SSP patients because they also had early-onset seizure post
      stroke, but without SSP. We compared the clinical presentations of the SSP
      patients with those of the non SSP patients including baseline stroke risk
      factors, and 10-year Kaplan-Meier death risk after their first stroke. RESULTS:
      In the SSP patients, 25.7% of them presented with posterior circulation
      infarction, whereas only 12.5% of the non SSP patients had this condition
      (P<0.05). In contrast, 17.1% of the SSP patients were being treated with
      antiepileptic drugs at discharge whereas 37.5% of the non SSP patients received
      such treatment (P<0.05). The percentage of SSP patients with temporal lobe
      lesions was less than in non SSP patients (P<0.05). However, brain stem and
      thalamus lesions were more frequently seen in SSP patients than non in SSP
      patients (P<0.05). The risk factors for ischemic stroke including a history of
      hypertension, diabetes mellitus, hyperlipidemia and atrial fibrillation were the
      same in these two groups (P>0.05). In the SSP patients group, the 10-year risk of
      death was 36.9% after the initial seizure incident, and in the non SSP patients
      group, the 10-year death risk was 40.1%, but this difference between the two
      groups was not significant (P>0.05). CONCLUSIONS: Ischemic stroke patients with
      SSP had some unique signs that included a higher incidence of posterior
      circulation infarction than non SSP patients.

PMID- 29571871
TI  - Nivolumab-induced myositis: A case report and a literature review.

PMID- 29571872
TI  - Alterations of regional homogeneity in freezing of gait in Parkinson's disease.
AB  - INTRODUCTION: Freezing of gait (FOG) is a serious complication in patients with
      Parkinson's disease (PD), and is more common in the late state of the disease.
      The high risk of falling in patients with FOG impacts their quality of life.
      OBJECTIVE: To explore altered neuroactivity related to cognitive and executive
      function of PD patients with FOG. METHODS: Fourteen PD patients with FOG (FOG+),
      20 PD patients without FOG (FOG-), and 18 normal controls (NC) were enrolled.
      Functional MRI data of all PD patients were collected during OFF medication
      state. Data were analyzed using software of DPARSF and REST. Resting brain
      activity was measured by regional homogeneity (ReHo). ANOVA test was performed
      for ReHo among FOG, PD, and NC groups. RESULTS: ReHo alterations of left
      supplementary motor area (SMA) (Brodmann 6), left superior frontal region
      (Brodmann 9), and the right putamen (Brodmann 48) were significantly different
      among the three groups. The ReHo values within left SMA (Brodmann 6) and left
      superior frontal region (Brodmann 9) were significantly decreased in FOG+
      patients compared with FOG- patients. CONCLUSION: Changes in neural hypoactivity
      within the frontal region and SMA appear to be associated with FOG in PD
      patients, which suggests that the mechanism underlying FOG may relate to
      disruption of execution and cognition.

PMID- 29571873
TI  - Transplantation of in vitro cultured endothelial progenitor cells repairs the
      blood-brain barrier and improves cognitive function of APP/PS1 transgenic AD
      mice.
AB  - To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well
      known that excessive deposition of Abeta in the brain is a crucial part of the
      pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has
      attracted much attention. Impairment of the blood-brain barrier (BBB) leads to
      abnormal amyloid-beta (Abeta) transport, and chronic cerebral hypoperfusion
      causes Abeta deposition throughout the onset and progression of AD. Endothelial
      progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our
      previous studies have shown that a reduced number of EPCs in the peripheral blood
      results in cerebral vascular repair disorder, cerebral hypoperfusion and
      neurodegeneration, which might be related to the cognitive dysfunction of AD
      patients. This study was designed to confirm whether EPCs transplantation could
      repair the blood-brain barrier, stimulate angiogenesis and reduce Abeta
      deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated
      in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent
      with previous studies, EPC transplants also increased the microvessel density. We
      observed that Abeta senile plaque deposition was decreased and hippocampal cell
      apoptosis was reduced after EPCs transplantation. The Morris water maze test
      showed that spatial learning and memory functions were significantly improved in
      mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression
      of tight junction proteins, repair BBB tight junction function, stimulate
      angiogenesis, promote Abeta clearance, and decrease neuronal loss, ultimately
      improve cognitive function. Taken together, these data demonstrate EPCs may play
      an important role in the therapeutic implications for vascular dysfunction in AD.

PMID- 29571874
TI  - Identification and treatment of the visual processing asymmetry in MS patients
      with optic neuritis: The Pulfrich phenomenon.
AB  - BACKGROUND: The Pulfrich phenomenon (PF) is the illusory perception that an
      object moving linearly along a 2-D plane appears to instead follow an elliptical
      3-D trajectory, a consequence of inter-eye asymmetry in the timing of visual
      object identification in the visual cortex; with optic neuritis as a common
      etiology. OBJECTIVE: We have designed an objective method to identify the
      presence and magnitude of the PF, in conjunction with a cooresponding strategy by
      which to abolish the effect; with monocular application of neutral density
      filters to the less affected fellow eye, in patients with MS and a history of
      optic neuropathy (e.g. related to acute optic neuritis or subclinical optic
      neuropathy). METHODS: Twenty-three MS patients with a history of acute unilateral
      or bilateral optic neuritis, and ten healthy control subjects (HC) were recruited
      to participate in a pilot study to assess our strategy. Subjects were asked to
      indicate whether a linearly moving pendulum ball followed a linear 2-D path
      versus an illusory 3-D elliptical object-motion trajectory, by reporting the
      ball's approximation to one of nine horizontally-oriented colored wires that were
      positioned parallel to one another and horizontal to the linear pendulum path.
      Perceived motion of the bob that moved along wires behind or in front (along the
      'Z' plane) of the middle reference wire indicated an illusory elliptical
      trajectory of ball motion consistent with the PF. RESULTS: When the neutral
      density filter titration was applied to the fellow eye the severity of the PF
      decreased, eventually being fully abolished in all but one patient. The magnitude
      of neutral density filtering required correlated to the severity of the patient's
      initial PF magnitude (p < 0.001). CONCLUSIONS: We ascertained the magnitude of
      the visual illusion associated with the PF, and the corresponding magnitude of
      neutral density filtering necessary to abolish it.

PMID- 29571875
TI  - Familial and sporadic chronic progressive degenerative parietal ataxia.
AB  - BACKGROUND & OBJECTIVE: Parietal ataxia has been mainly reported as a consequence
      of acute ischemic stroke, while degenerative parietal ataxia has not been
      reported. METHODS: We investigated clinical characteristics, neuroimaging data,
      and genetic analysis of patients with cerebellar ataxia plus parietal atrophy.
      RESULTS: We identified seven patients, including five patients from two families,
      with chronic progressive cerebellar ataxia due to degenerative parietal atrophy
      but not stroke. Age at onset of ataxia was 57.6 +/- 6.9 years. All patients
      showed chronic progressive cerebellar ataxia with severity of ataxic gait > limb
      ataxia > dysarthria. Patients showed no cognitive dysfunction, muscle weakness,
      or parkinsonism, and only two patients showed mild sensory disturbances. The
      seven patients showed lateralized limb ataxia with greater contralateral parietal
      lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon
      emission computed tomography, without any abnormal cerebellar pathology (i.e.,
      crossed cerebellar diaschisis). Pathogenic mutations in the microtubule
      associated protein tau gene were not found using two single nucleotide
      polymorphisms. CONCLUSIONS: This is the first description showing unique clinical
      features of familial and sporadic chronic progressive degenerative parietal
      ataxia.

PMID- 29571876
TI  - Normal tendon reflexes despite absent sensory nerve action potentials in CANVAS:
      a neurophysiological study.
AB  - CANVAS is a recently defined progressive ataxic syndrome with impairment of
      vestibular, somatosensory and cerebellar function due to atrophic degeneration of
      dorsal root ganglia and dorsal columns, of cranial nerve somatosensory ganglia,
      of vestibular ganglia and vestibular nerves and of cerebellar Purkinje cells.
      While all patients eventually develop sensory impairment in a non-length
      dependent pattern and lose sensory nerve action potentials, some retain their
      tendon reflexes. Here we study 5 CANVAS patients with absent sensory nerve action
      potentials but intact, even brisk Achilles tendon reflexes and, in 4, preserved H
      reflexes in the upper and lower limbs. These findings imply that dorsal root
      ganglion neurons subserving cutaneous afferents more vulnerable than those
      subserving muscle afferents. Our findings have a clinical message: preservation
      of the Achilles tendon jerk does not exclude a large fibre peripheral
      neuronopathy.

PMID- 29571877
TI  - 'The shock of diagnosis': Qualitative accounts from people with Motor Neurone
      Disease reflecting the need for more person-centred care.
AB  - The diagnosis of Motor Neurone Disease (MND) is devastating for people with MND
      (PwMND) and their families. The objective of this study is to describe the
      experiences of PwMND in receiving the diagnosis in order to inform a more person
      centred approach to communicating such bad news. The design was an anonymous
      postal survey facilitated by all MND associations across Australia (2014-15).
      Survey questions centred on the SPIKES protocol for communicating bad news; each
      question contained an area for written responses, which were thematically
      analysed for content. Two hundred and forty-eight responses were received from
      people with MND (29% response rate). Four themes emerged: challenges in being
      diagnosed with MND; the emotions experienced; the good and the bad; and links to
      further information and support. Receiving such a diagnosis requires preparation,
      forethought, sensitive and individualised care on the part of the neurologist,
      including where and how the diagnosis is given; the supports required; and
      timing, amounts and sources of giving information. The emotional reactions of the
      neurologist also caused a lasting impression on those receiving the diagnosis.
      This study could form the basis for best practice programs implementing a more
      person-centred approach to caring for PwMND right from the diagnosis stage. The
      focus needs to shift on the person's values, preferences, psychosocial and
      existential concerns in the context of the underlying disease experience and the
      manner clinical practice is delivered.

PMID- 29571878
TI  - Expression analysis of protein homeostasis pathways in the peripheral blood
      mononuclear cells of sporadic amyotrophic lateral sclerosis patients.
AB  - Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis
      (ALS) which suggests involvement of protein homeostasis pathways in etiology of
      ALS. However, status of protein homeostasis in peripheral blood of ALS is not
      well established. We analyzed expression levels of key genes of proteostasis
      pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS)
      patients and healthy controls. Increased protein carbonylation was observed in
      patients reflecting oxidative damage in PBMCs. We observed increased transcript
      and protein levels of GRP78 suggesting Endoplasmic reticulum (ER) insult to
      cells. Further, significant upregulation of spliced XBP1 and two stress sensors:
      IRE1alpha/ERN1 and ATF6 indicated induction of unfolded protein response (UPR).
      Genes involved in autophagosome initiation (ULK1, ULK2, ATG13); nucleation and
      elongation (BECLIN1, ATG7, ATG16L1, ATG5, ATG10) and vesicular trafficking genes
      were significantly increased in patients. Increased lipidation of LC3 validated
      induction of autophagy. Accumulation of low molecular weight ubiquitinated
      proteins in patients suggested deregulation of proteasome (UPS) pathway. In
      addition, cytosolic chaperones (HSP70 and HSP27) and HSF1 were elevated in
      patients. Increased TDP43 indicated role of TDP43 in disease pathology. Our
      findings suggest that there is oxidative insult and upregulation of UPR,
      vesicular trafficking and autophagy in PBMCs of sALS patients.

PMID- 29571879
TI  - How can we restore cognitive deficits in patients with cerebellar damages?

PMID- 29571880
TI  - Pilot trial of a tele-rehab intervention to improve outcomes after stroke in
      Ghana: A feasibility and user satisfaction study.
AB  - BACKGROUND: Tele-rehabilitation after stroke holds promise for under-resourced
      settings, especially sub-Saharan Africa (SSA), with its immense stroke burden and
      severely limited physical therapy services. OBJECTIVE: To preliminarily assess
      the feasibility and outcomes of mobile technology-assisted physical therapy
      exercises for stroke survivors in Ghana. METHODS: We conducted a prospective,
      single arm, pre-post study involving 20 stroke survivors recruited from a
      tertiary medical center, who received a Smartphone with the 9zest Stroke App(r)
      to deliver individualized, goal-targeted 5-days-a-week exercise program that was
      remotely supervised by a tele-therapist for 12 weeks. Outcome measures included
      changes in stroke levity scale scores (SLS), Modified Rankin score (MRS),
      Montreal Cognitive Assessment (MOCA), and feasibility indicators. RESULTS: Among
      study participants, mean +/- SD age was 54.6 +/- 10.2 years, 11 (55%) were men,
      average time from stroke onset was 6 months. No participants dropped out.
      Compared with baseline status, mean +/- SD scores on SLS improved from 7.5 +/-
      3.1 to 11.8 +/- 2.2 at month 1 (p < 0.0001) and 12.2 +/- 2.4 at month 3 (p <
      0.0001), MOCA scores improved from 18.2 +/- 4.3 to 20.4 +/- 4.7 at month 1 (p =
      0.14), and 22.2 +/- 7.6 at month 3 (p = 0.047). Mean +/- SD weekly sessions
      performed by participants per month was 5.7 +/- 5.8 and duration of sessions was
      25.5 +/- 16.2 min. Erratic internet connectivity negatively affected full
      compliance with the intervention, although satisfaction ratings by study
      participants were excellent. CONCLUSION: It is feasible to administer an m-health
      delivered physical therapy intervention in SSA, with high user satisfaction.
      Randomized trials to assess the efficacy and cost-effectiveness of this
      intervention are warranted.

PMID- 29571881
TI  - Neutrophil-to-lymphocyte ratio improves outcome prediction of acute intracerebral
      hemorrhage.
AB  - BACKGROUND: The inflammatory response plays a role in determining the course of
      intra-cerebral hemorrhage (ICH) and immune parameters may have prognostic value.
      The aim of the study was to determine whether the peripheral leukocyte counts and
      neutrophil-to-lymphocyte ratio (NLR) were associated to 30-day functional status
      after ICH, and improved the accuracy of outcome prediction when added to the
      Modified ICH score. METHODS: We retrospectively identified consecutive patients
      with spontaneous ICH who underwent blood sampling and cranial CT neuroimaging
      within 24 h from onset. Total white blood cells (WBC), absolute neutrophil count
      (ANC) and absolute lymphocyte count (ALC) were collected, and the NLR computed as
      the ANC to ALC ratio. The study endpoint was 30-day functional status; poor
      outcome was defined as death or major disability (modified Rankin Scale score >=
      3). RESULTS: Two hundred and eight patients were enrolled, of which 111 (53.4%)
      had a modified Rankin Scale score >= 3 at 30 days from ICH. At multivariate
      analysis, the WBC (adjusted odd ratio [adjOR] for 1000 leukocytes increase 1.20,
      95% confidence interval [CI] 1.05-1.38), ANC (adjOR for 1000 neutrophils increase
      1.34, 95% CI 1.14-1.57), ALC (adjOR for 1000 lymphocytes increase 0.34, 95% CI
      0.20-0.59) and NLR (adjOR for 1-point increase 1.49, 95% CI 1.24-1.79) were
      independently associated with 30-day poor outcome. Predictive accuracy of the
      Modified ICH score was enhanced by adding the NLR. CONCLUSIONS: The NLR was
      associated with 30-day mortality and morbidity after ICH, and improved the
      accuracy of outcome prediction when added to the Modified ICH score.

PMID- 29571882
TI  - Coming into Focus: Mechanisms of Microtubule Minus-End Organization.
AB  - Microtubule organization has a crucial role in regulating cell architecture. The
      geometry of microtubule arrays strongly depends on the distribution of sites
      responsible for microtubule nucleation and minus-end attachment. In cycling
      animal cells, the centrosome often represents a dominant microtubule-organizing
      center (MTOC). However, even in cells with a radial microtubule system, many
      microtubules are not anchored at the centrosome, but are instead linked to the
      Golgi apparatus or other structures. Non-centrosomal microtubules predominate in
      many types of differentiated cell and in mitotic spindles. In this review, we
      discuss recent advances in understanding how the organization of centrosomal and
      non-centrosomal microtubule networks is controlled by proteins involved in
      microtubule nucleation and specific factors that recognize free microtubule minus
      ends and regulate their localization and dynamics.

PMID- 29571883
TI  - Re: Exploring the experiences and implementing strategies for physical therapy
      students who perceive they have been bullied or harassed on clinical placements:
      participatory action research.

PMID- 29571884
TI  - Nickel-titanium springs probably result in a small increase in orthodontic space
      closure rate compared with elastomeric power chains, but insufficient or no
      evidence about relative effects on other outcomes.

PMID- 29571885
TI  - Direct pulp capping with Biodentine seems to have an acceptable success rate
      after 1 to 1.5 years.

PMID- 29571886
TI  - Acupuncture seems to result in a higher reduction in pain compared with a single
      400 milligram dose of ibuprofen in patients with irreversible pulpitis.

PMID- 29571887
TI  - Combination of Gow-Gates and inferior alveolar nerve block may result in a higher
      rate of successful anesthesia than either technique alone.

PMID- 29571888
TI  - Evaluation of the quality of life in patients followed for differentiated cancer
      of the thyroid.
AB  - Thyroid cancer often has good prognosis but can impact quality of life. The
      objective of this study is to evaluate quality of life in patients treated for
      differentiated thyroid carcinoma and look for associated factors. An
      observational cross-sectional study with comparison group was conducted in the
      Endocrinology Department of the Ibn Rochd University Hospital between October
      2013 and February 2015. The patient group included 124 adult patients followed
      for differentiated thyroid carcinoma; the control group comprised 124 healthy
      subjects of the same age. Quality of life was evaluated by 3 questionnaires
      validated in Arabic: SF36, Hamilton anxiety and Hamilton depression. Patients'
      quality of life was significantly impaired compared to controls on the two
      Hamilton and all SF36 scores. Factors influencing quality of life were TNM stage,
      radioiodine therapy and dose, and the presence of metastases. The psychological
      management of patients with thyroid cancer is an essential point always to be
      considered, especially in the presence of risk factors for impaired quality of
      life.

PMID- 29571889
TI  - Nationwide questionnaire-based survey of oral immunotherapy in Japan.
AB  - BACKGROUND: Clinical trials on oral immunotherapy (OIT) have been increasing for
      nearly a decade; however, several national guidelines do not recommend OIT as a
      standardized procedure. The aim of this study was to obtain insights into the
      current use and practice of OIT in Japan. METHODS: A first questionnaire was
      mailed to 524 training and teaching facilities of the Japan Pediatric Society.
      The first survey requested information on the implementation of OIT, whereas the
      second survey aimed to gather more detailed information on OIT, such as its
      safety. RESULTS: In total, 360 facilities (69%) responded to the survey; among
      them, 102 (28%) provided OIT to 7973 patients [1544 received OIT while
      hospitalized (inpatient OIT), whereas 6429 received OIT without hospitalization
      (outpatient OIT)]. Approval for OIT was obtained from an ethics committee or
      institutional review board in 89% and 31% of facilities for inpatient and
      outpatient OIT, respectively. In inpatient OIT, immediate allergic reactions
      requiring treatment occurred in 68% of patients while hospitalized, and in
      another 56%, following discharge. In contrast, 11% of patients developed
      immediate allergic reactions in outpatient OIT. Adrenaline injections at home
      were required in 2%. Sixteen patients developed adverse reactions other than
      immediate allergic reactions, among which eosinophilic gastroenteritis was most
      common. CONCLUSIONS: OIT is widely provided not only as clinical research but
      also as general practice in Japan. However, because there is a high risk of
      developing anaphylaxis at home, OIT should be conducted carefully as in a
      clinical research setting taking safety into consideration.

PMID- 29571890
TI  - Response of humic acid formation to elevated nitrate during chicken manure
      composting.
AB  - Nitrate can stimulate microbes to degrade aromatic compounds, whereas humic acid
      (HA) as a high molecular weight aromatic compound, its formation may be affected
      by elevated nitrate during composting. Therefore, this study is conducted to
      determine the effect of elevated nitrate on HA formation. Five tests were
      executed by adding different nitrate concentrations to chicken manure composting.
      Results demonstrate that the concentration of HA in treatment group is
      significantly decreased compared with control group (p < 0.05), especially in the
      highest nitrate concentration group. RDA indicates that the microbes associated
      with HA and environmental parameters are influenced by elevated nitrate.
      Furthermore, structural equation model reveals that elevated nitrate reduces HA
      formation by mediating microbes directly, or by affecting ammonia and pH as the
      indirect drivers to regulate microbial community structure.

PMID- 29571891
TI  - New insights in photosynthetic microbial fuel cell using anoxygenic phototrophic
      bacteria.
AB  - Anoxygenic phototrophic bacteria (APB) pay a key role in biogeochemical cycles,
      and it can convert light energy to chemical energy by photosynthesis process.
      Photosynthetic microbial fuel cell (photo-MFC) is regarded as a promising energy
      harvesting technology, which is also applied to environment treatment in recent
      years. The previous studies show that photo-MFC with APB have higher power putout
      than other bioelectrochemical systems. However, photo-MFC with APB is not
      reviewed due to some limited factors in the development process. In this review,
      photo-MFC with APB is treated according to its electron transfer pathways, the
      current understanding, APB strains, application, influence of substrates, and
      economic assessment. Meanwhile, knowledge of photosynthesis components and
      electron transfer pathways of APB is crucial for developing new energy and easing
      the serious energy crisis. Moreover, some new insights (the optimization of light
      source and self-sustaining bioelectricity generation) are proposed for the future
      explorations.

PMID- 29571892
TI  - Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health: A Comprehensive
      Review.
AB  - The potential cardiovascular (CV) disease (CVD) benefits of Omega-3
      Polyunsaturated Fatty Acids (OM3) have been intensely studied and debated for
      decades. Initial trials were performed in patients with low use of maximal
      medical therapy for CVD, and reported significant mortality benefits with the use
      of 1 g/day OM3 intervention following myocardial infarction (MI). More recent
      studies, including cohorts of patients receiving modern guideline directed
      medical therapy for CVD, have often not shown similar benefits with OM3 use. We
      conducted a literature review using PubMed, professional society guidelines,
      specific journal databases including New England Journal of Medicine and Journal
      of the American College of Cardiology from January 1, 2007 to December 31, 2017.
      References from selected articles were also reviewed, as well as key articles
      outside of the selected time-frame for their important findings or historical
      perspectives. Currently, there are no Class I recommendations from the American
      Heart Association (AHA) for the use of OM3, however, considering the safety of
      this therapy and beneficial findings of some modern studies (including patients
      with current maximal medical therapy for CVD), the AHA has recently expanded
      their list of Class II recommendations, in which treatment with OM3 for CVD
      benefit is reasonable. This review discusses the current state of the evidence,
      summarizes current professional recommendations, and provides recommendations for
      future research.

PMID- 29571893
TI  - Air pollution is associated with the development of atherosclerosis via the
      cooperation of CD36 and NLRP3 inflammasome in ApoE-/- mice.
AB  - Previous studies have indicated that the main air pollutant fine particulate
      matter (<=2.5 MUm; PM2.5) exposure is associated with the development of
      atherosclerosis. Although the mechanism is not fully illustrated, the
      inflammatory responses play an important role. The present study aimed to explore
      whether PM2.5-exacerbated atherosclerosis was mediated by the cooperation of
      cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization
      domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E-/- (ApoE-/
      ) mice. Thirty-two ApoE-/- mice were randomly divided into two groups. One group
      was fed with high fat chow (HFC) for 10 weeks to establish atherosclerotic model,
      and the other was fed with normal chow (NC). From week 11, the mice were exposed
      to concentrated PM2.5 (PM) or filtered air (FA) using Shanghai Meteorological and
      Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups,
      PM2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM
      mice appeared higher lipid content in the aortic root than that in the FA mice.
      Compared with the FA mice, PM mice appeared a decrease in high density
      lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in
      apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low
      density lipoprotein (ox-LDL). Moreover, PM2.5 exposure induced increase of CD36
      in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation
      related indicators were activated or increased in the aorta of the PM mice when
      compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome
      activation may be the potential mechanisms linkixposed to concentrated PM2.5 (PM)
      or filtered air (FA) using Shanghai Meteorological and Environmental Animal
      Exposure System for 16 weeks. In both NC and HFC groups, PM2.5 exposure induced
      the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid
      content in the aortic root than that in the FA mice. Compared with the FA mice,
      PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and
      apolipoprotein A1 along with an increase in apolipoprotein B, low density
      lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL).
      Moreover, PM2.5 exposure induced increase of CD36 in serum and aorta. In both NC
      and HFC groups, NLRP3 inflammasome activation-related indicators were activated
      or increased in the aorta of the PM mice when compared with the FA mice. The
      cooperation of CD36 and NLRP3 inflammasome activation may be the potential
      mechanisms linking air pollution and HFC-induced atherosclerosis even in the mice
      with NC intake.

PMID- 29571895
TI  - Low dose cadmium upregulates the expression of von Willebrand factor in
      endothelial cells.
AB  - Cadmium (Cd) is a persistent and widespread environmental pollutant of continuing
      worldwide concern. Previous studies have suggested that Cd exposure increases the
      risk of cardiovascular diseases, such as atherosclerosis and hypertension.
      However, the underlying mechanisms are poorly understood. In this study, we
      observed that low dose Cd treatment induced von Willebrand factor (vWF)
      expression in vascular endothelial cells in mouse lung and kidney tissues. In
      vitro analysis showed that 1 MUM Cd specifically upregulated vWF mRNA and protein
      expression in human umbilical vein endothelial cells (HUVECs), indicating that Cd
      targets vascular endothelial cells even at relatively low concentrations. Further
      study demonstrated that nuclear factor kappa B (NF-kappaB) and GATA3, two
      established transcription regulators of the vWF gene, were not altered in the
      presence of Cd. However, ETS-related gene (ERG) was significantly induced by 1
      MUM Cd. When ERG was knocked down by siRNA, Cd induced upregulation of vWF was
      totally blocked. Chromatin immunoprecipitation (ChIP) assay showed that Cd
      increases the binding of ERG on the -56 ETS motif on the human vWF promoter.
      These results indicated that ERG mediated the increased expression of vWF by Cd.
      Since vWF is a key regulator for vascular homeostasis, our findings may provide a
      novel mechanism for understanding low dose Cd induced development of vascular
      diseases.

PMID- 29571894
TI  - Effects of developmental lead exposure on the hippocampal methylome: Influences
      of sex and timing and level of exposure.
AB  - Developmental lead (Pb) exposure results in persistent cognitive/behavioral
      impairments as well as an elevated risk for developing a variety of diseases in
      later life. Environmental exposures during development can result in a variety of
      epigenetic changes, including alterations in DNA methylation, that can influence
      gene expression patterns and affect the function and development of the nervous
      system. The present promoter-based methylation microarray profiling study
      explored the extent to which developmental Pb exposure may modify the methylome
      of a brain region, hippocampus, known to be sensitive to the effects of Pb
      exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375
      ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation),
      early postnatal exposures (birth through weaning), or long-term postnatal
      exposures (birth through postnatal day 55). Results showed a significant
      contribution of sex to the hippocampal methylome and effects of Pb exposure
      level, with non-linear dose response effects on methylation. Surprisingly, the
      developmental period of exposure contributed only a small amount of variance to
      the overall data and gene ontology (GO) analysis revealed the largest number of
      overrepresented GO terms in the groups with the lowest level of exposure. The
      highest number of significant differentially methylated regions was found in
      females exposed to Pb at the lowest exposure level. Our data reinforce the
      significant effect that low level Pb exposure may have on gene-specific DNA
      methylation patterns in brain and that this occurs in a sex-dependent manner.

PMID- 29571896
TI  - Validation of an automated counting procedure for phthalate-induced testicular
      multinucleated germ cells.
AB  - In utero exposure to certain phthalate esters results in testicular toxicity,
      characterized at the tissue level by induction of multinucleated germ cells
      (MNGs) in rat, mouse, and human fetal testis. Phthalate exposures also result in
      a decrease in testicular testosterone in rats. The anti-androgenic effects of
      phthalates have been more thoroughly quantified than testicular pathology due to
      the significant time requirement associated with manual counting of MNGs on
      histological sections. An automated counting method was developed in ImageJ to
      quantify MNGs in digital images of hematoxylin-stained rat fetal testis tissue
      sections. Timed pregnant Sprague Dawley rats were exposed by daily oral gavage
      from gestation day 17 to 21 with one of eight phthalate test compounds or corn
      oil vehicle. Both the manual counting method and the automated image analysis
      method identified di-n-butyl phthalate, butyl benzyl phthalate, dipentyl
      phthalate, and di-(2-ethylhexyl) phthalate as positive for induction of MNGs.
      Dimethyl phthalate, diethyl phthalate, the brominated phthalate di-(2-ethylhexyl)
      tetrabromophthalate, and dioctyl terephthalate were negative. The correlation
      between automated and manual scoring metrics was high (r = 0.923). Results of MNG
      analysis were consistent with these compounds' anti-androgenic activities, which
      were confirmed in an ex vivo testosterone production assay. In conclusion, we
      have developed a reliable image analysis method that can be used to facilitate
      dose-response studies for the reproducible induction of MNGs by in utero
      phthalate exposure.

PMID- 29571897
TI  - Complex interplay of multiple biological systems that contribute to post-stroke
      infections.
AB  - Stroke is a leading contributor of death and disability around the world. Despite
      its recognised debilitating neurological deficits, a devastating clinical
      complication of surviving stroke patients that needs more attention is infection.
      Up to half of the patients develop infections after stroke, and a high proportion
      of them will die as a direct consequence. Major clinical trials that examined
      preventive antibiotic therapy in stroke patients have demonstrated this method of
      prevention is not effective as it does not reduce incidence of post-stroke
      pneumonia or improve patient outcome. Additionally, retrospective studies
      evaluating the use of beta-blockers for the modulation of the sympathetic nervous
      system to prevent post-stroke infections have given mixed results. Therefore,
      there is an urgent need for more effective therapeutic options that target the
      underlying mechanisms of post-stroke infections. The understanding that
      infections are largely attributable to the "stroke-induced systemic
      immunosuppression" phenomenon has begun to emerge, and thus, exploring the
      pathways that trigger post-stroke immunosuppression is expected to reveal
      potential new therapeutics. As such, we will outline the impacts that stroke has
      on several biological systems in this review, and discuss how these contribute to
      host susceptibility to infection after stroke. Furthermore, the emerging role of
      the gut and its microbiota has recently come to surface and intensifies the
      complex pathways to post-stroke infection. Finally, we identify potential avenues
      to combat infection that target the pathways of stroke-induced systemic
      immunosuppression to ultimately improve stroke patient outcome.

PMID- 29571899
TI  - Corrigendum to 'Panton-Valentine Leucocidin (PVL) Staphylococcus aureus a
      position statement from the International Society of Chemotherapy' [International
      Journal of Antimicrobial Agents 51/1 (2018) 16-25].

PMID- 29571900
TI  - Invitation letter with a standardized form is a reliable tool to exclude
      increased risk patients from organized fecal immunological testing-based
      colorectal cancer screening program.
AB  - In Europe, screening guidelines for colorectal cancer (CRC) recommend colonoscopy
      for high-risk patients and fecal immunological testing (FIT) for the standard
      risk group. Currently, there is not any validated screening tool to exclude high
      risk patients. The aim of the study is to evaluate the validity of exclusion and
      evaluate the follow-up of patients identified as increased risk for CRC. In this
      retrospective study using a prospective database, patients at increased risk were
      identified using the standardized form and then excluded from the FIT screening
      invitation. A specific questionnaire was sent to all patients at increased risk
      in order to confirm the reason for the exclusion and evaluate their follow-up.
      Among 220 695 eligible individuals, 16 693 (7.5%) were excluded after being
      characterized at increased risk using the standardized form. The questionnaire
      was sent to these 16.693 excluded patients and completed by 5076 (30.7%)
      patients. Validity of exclusion was confirmed in 92% of cases. Endoscopic follow
      up was in agreement with guideline in 89% of persons at increased risk
      (inflammatory bowel disease 93%, personal history of CCR 92%, of colonic polyps
      82%, family history of CRC 77%). This study suggests that the standardized form
      is a reliable tool to correctly exclude from the screening program 92% of
      patients at increased risk for CRC.

PMID- 29571901
TI  - Disease genes prediction by HMM based PU-learning using gene expression profiles.
AB  - Predicting disease candidate genes from human genome is a crucial part of
      nowadays biomedical research. According to observations, diseases with the same
      phenotype have the similar biological characteristics and genes associated with
      these same diseases tend to share common functional properties. Therefore, by
      applying machine learning methods, new disease genes are predicted based on
      previous ones. In recent studies, some semi-supervised learning methods, called
      Positive-Unlabeled Learning (PU-Learning) are used for predicting disease
      candidate genes. In this study, a novel method is introduced to predict disease
      candidate genes through gene expression profiles by learning hidden Markov
      models. In order to evaluate the proposed method, it is applied on a mixed part
      of 398 disease genes from three disease types and 12001 unlabeled genes. Compared
      to the other methods in literature, the experimental results indicate a
      significant improvement in favor of the proposed method.

PMID- 29571898
TI  - Differential immune responses and microbiota profiles in children with autism
      spectrum disorders and co-morbid gastrointestinal symptoms.
AB  - OBJECTIVES: Many studies have reported the increased presence of gastrointestinal
      (GI) symptoms in children with autism spectrum disorders (ASD). Altered
      microbiome profiles, pro-inflammatory responses and impaired intestinal
      permeability have been observed in children with ASD and co-morbid GI symptoms,
      yet few studies have compared these findings to ASD children without GI issues or
      similarly aged typical developing children. The aim of this study was to
      determine whether there are biological signatures in terms of immune dysfunction
      and microbiota composition in children with ASD with GI symptoms. METHODS:
      Children were enrolled in one of four groups: ASD and GI symptoms of irregular
      bowel habits (ASDGI), children with ASD but without current or previous GI
      symptoms (ASDNoGI), typically developing children with GI symptoms (TDGI) and
      typically developing children without current or previous GI symptoms (TDNoGI).
      Peripheral blood mononuclear cells (PBMC) were isolated from the blood,
      stimulated and assessed for cytokine production, while stool samples were
      analyzed for microbial composition. RESULTS: Following Toll-Like receptor (TLR)-4
      stimulation, the ASDGI group produced increased levels of mucosa-relevant
      cytokines including IL-5, IL-15 and IL-17 compared to ASDNoGI. The production of
      the regulatory cytokine TGFbeta1 was decreased in the ASDGI group compared with
      both the ASDNoGI and TDNoGI groups. Analysis of the microbiome at the family
      level revealed differences in microbiome composition between ASD and TD children
      with GI symptoms; furthermore, a predictive metagenome functional content
      analysis revealed that pathways were differentially represented between ASD and
      TD subjects, independently of the presence of GI symptoms. The ASDGI also showed
      an over-representation of the gene encoding zonulin, a molecule regulating gut
      permeability, compared to the other groups. CONCLUSIONS: Overall our findings
      suggest that children with ASD who experience GI symptoms have an imbalance in
      their immune response, possibly influenced by or influencing metagenomic changes,
      and may have a propensity to impaired gut barrier function which may contribute
      to their symptoms and clinical outcome.

PMID- 29571902
TI  - Ileal conduit vs orthotopic neobladder: Which one offers the best health-related
      quality of life in patients undergoing radical cystectomy? A systematic review of
      literature and meta-analysis.
AB  - INTRODUCTION: Orthotopic neobladder (ONB) and ileal conduit (IC) are the most
      commonly practiced techniques of urinary diversion (UD) after radical cystectomy
      (RC) in bladder cancer patients. Data in the literature is still discordant
      regarding which UD technique offers the best HR-QoL. OBJECTIVE: The objective was
      to compare HR-QoL in patients undergoing ONB and IC after RC, through a
      systematic review of the literature and meta-analysis. MATERIAL AND METHODS: We
      performed a literature search of PubMed, ScienceDirect, CochraneLibrary and
      ClinicalTrials.Gov in September 2017 according to the Cochrane Handbook and the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. The studies
      were evaluated according to the "Oxford Center for Evidence-Based Medicine"
      criteria. The outcome measures evaluated were subdomains' scores of Bladder
      Cancer Index BCI: urinary function (UF), urinary bother (UB), bowel function
      (BF), bowel bother (BB), sexual function (SF) and sexual bother (SB). Continuous
      outcomes were compared using weighted means differences, with 95% confidence
      intervals. The presence of publication bias was examined by funnel plots.
      RESULTS: Four studies met the inclusion criteria. The pooled results demonstrated
      better UF and UB scores in IC patients: differences were -18.17 (95% CI: -27.49, 
      8.84, P=0.0001) and -3.72 (95% CI: -6.66, -0.79, P=0.01) respectively. There was
      no significant difference between IC and ONB patients in terms of BF and BB. SF
      was significantly better in ONB patients: the difference was 12.7 (95% CI, 6.32,
      19.08, P<0.0001). However no significant difference was observed regarding SB.
      CONCLUSION: This meta-analysis of non-randomized studies demonstrated a better HR
      QoL in urinary outcomes in IC patients compared with ONB patients.

PMID- 29571903
TI  - A state-of-the-art review on nitrous oxide control from waste treatment and
      industrial sources.
AB  - This review aims at holistically analyzing the environmental problems associated
      with nitrous oxide (N2O) emissions by evaluating the most important sources of
      N2O and its environmental impacts. Emissions from wastewater treatment processes
      and the industrial production of nitric and adipic acid represent nowadays the
      most important anthropogenic point sources of N2O. Therefore, state-of-the-art
      strategies to mitigate the generation and release to the atmosphere of this
      greenhouse and O3-depleting gas in the waste treatment and industrial sectors are
      also reviewed. An updated review of the end-of-the-pipe technologies for N2O
      abatement, both in the waste treatment and industrial sectors, is herein
      presented and critically discussed for the first time. Despite the consistent
      efforts recently conducted in the development of cost-efficient and eco-friendly
      N2O abatement technologies, physical/chemical technologies still constitute the
      most popular treatments for the control of industrial N2O emissions at commercial
      scale. The recent advances achieved on biological N2O abatement based on
      heterotrophic denitrification have opened new opportunities for the development
      of eco-friendly alternatives for the treatment of N2O emissions. Finally, the
      main limitations and challenges faced by these novel N2O abatement
      biotechnologies are identified in order to pave the way for market
      implementation.

PMID- 29571904
TI  - Assessment of dosimetric errors induced by deformable image registration methods
      in 4D pencil beam scanned proton treatment planning for liver tumours.
AB  - PURPOSE: Respiratory impacts in pencil beam scanned proton therapy (PBS-PT) are
      accounted by extensive 4D dose calculations, where deformable image registration
      (DIR) is necessary for estimating deformation vector fields (DVFs). We aim here
      to evaluate the dosimetric errors induced by different DIR algorithms in their
      resulting 4D dose calculations by using ground truth(GT)-DVFs from 4DMRI.
      MATERIALS AND METHODS: Six DIR methods: ANACONDA, Morfeus, B-splines, Demons, CT
      Deformable, and Total Variation, were respectively applied to nine 4DCT-MRI liver
      data sets. The derived DVFs were then used as input for 4D dose calculation. The
      DIR induced dosimetric error was assessed by individually comparing the resultant
      4D dose distributions to those obtained with GT-DVFs. Both single-/three-field
      plans and single/rescanned strategies were investigated. RESULTS: Differences in
      4D dose distributions among different DIR algorithms, and compared to the results
      using GT-DVFs, were pronounced. Up to 40 % of clinically relevant dose
      calculation points showed dose differences of 10 % or more between the GT.
      Differences in V95(CTV) reached up to 11.34 +/- 12.57 %. The dosimetric errors
      became in general less substantial when applying multiple-field plans or using
      rescanning. CONCLUSION: Intrinsic geometric errors by DIR can influence the
      clinical evaluation of liver 4D PBS-PT plans. We recommend the use of an error
      bar for correctly interpreting individual 4D dose distributions.

PMID- 29571905
TI  - An Ancestral Gibberellin in a Moss Physcomitrella patens.

PMID- 29571906
TI  - [Emergency eye care in French university hospitals].
AB  - INTRODUCTION: The patient's request for urgent care in ophthalmology (PRUCO) at
      health care centers is constantly growing. In France, university hospitals are
      managing 75% of these cases. We sought to quantify PRUCO referred to French
      university hospital emergency units as well as to approach the structure and the
      territorial distribution of emergency eye care provided by French university
      hospitals. METHODS: We conducted a quick cross-sectional survey sent to the 32
      metropolitan and overseas French university hospitals. It inquired for each
      hospital whether emergency eye care units were available, whether
      ophthalmologists were on duty or on call overnight and how many PRUCO were
      managed in 2016. RESULTS: The 32 university hospitals completed the survey. A
      total of 398650 PRUCO were managed in French university hospitals in 2016. The
      emergency unit was exclusively dedicated to eye care for 70% of the hospitals,
      with 47% (15/32) of them employing an ophthalmologist on duty overnight. Every
      hospital but one had at least one ophthalmologist on call. The city of Paris set
      aside, university hospitals took care of an annual mean of 9000 PRUCO (min=500;
      max=32,250). CONCLUSION: The 32 French university hospitals are actively
      responding to patient's requests for urgent care in ophthalmology with very
      heterogeneous patient volumes and organizational systems. Half of them employ
      ophthalmologists on duty.

PMID- 29571907
TI  - The Effects of Endodontic Access Cavity Preparation Design on the Fracture
      Strength of Endodontically Treated Teeth: Traditional Versus Conservative
      Preparation.
AB  - INTRODUCTION: The aim of this study was to compare the fracture strengths of
      mandibular molar teeth prepared using traditional endodontic cavity (TEC) and
      conservative endodontic cavity (CEC) methods and restored using SDR (Dentsply
      Caulk, Milford, DE) and EverX Posterior (GC Dental, Tokyo, Japan) base composite
      materials. METHODS: A hundred mandibular first molar teeth were randomly divided
      into 5 groups. In group 1 (the control group), samples were kept intact. In group
      2, TECs were prepared, and the samples were restored with EverX Posterior and
      composite resin. In group 3, CECs were prepared, and the samples were restored
      with EverX Posterior and composite resin. In group 4, TECs were prepared, and the
      samples were restored with SDR and composite resin. In group 5, CECs were
      prepared, and the samples were restored with SDR and composite resin. This load
      was applied on the samples at 1-mm/min speed using a 6-mm round-head tip until
      fracture. The forces resulting in fracture were recorded in newton units. The
      data were analyzed using Kruskal-Wallis and Pearson correlation tests at a 5%
      significance level. RESULTS: The fracture strengths of the samples in the control
      group were significantly higher than the experimental groups (P < .05). There was
      no statistically significant difference in the endodontic access cavities
      prepared used the TEC and CEC methods and restored using the same composite base
      material (P > .05). CONCLUSIONS: CEC preparation did not increase the fracture
      strength of teeth with class II cavities compared with TEC preparation. The
      fracture strength of teeth restored with the SDR bulk-fill composite was higher
      than that of teeth restored with EverX Posterior.

PMID- 29571908
TI  - Comparison of the Volume of Root Canal Irrigant Collected by 2 Negative Pressure
      Needles at Different Flow Rates of Delivery.
AB  - INTRODUCTION: A greater irrigant volume improves the effectiveness of root canal
      irrigation. The purpose of this study was to compare 2 negative pressure systems
      regarding the volume of irrigant collected from the apical area in moderately
      curved canals at 3 different flow rates of delivery in vitro. METHODS: The
      mesiobuccal canals of 30 molars with a curvature between 20 degrees  and 40
      degrees  were prepared to size #40.04 taper. A closed system was created. The
      canals were irrigated at 3, 6, and 12 mL/min for 30 seconds using EndoVac
      (SybronEndo, Orange, CA) and the INP needle (Mixnus Fine Engineering Co Ltd,
      Nagano, Japan) (both independent variables). A recovery trap was used to collect
      the irrigant aspirated by the negative pressure needles. Irrigant volume
      (dependent variable) was measured in milliliters. Data were analyzed using mixed
      analysis of variance. RESULTS: There was a statistically significant interaction
      between the negative pressure system and the irrigant volume collected (P <
      .0005). The mean irrigant volume collected by the different negative pressure
      systems was greater for INP at 3 (P < .001), 6 (P < .001), and 12 mL/min (P <
      .001) flow rate. Both negative pressure needles showed statistically significant
      differences (P < .001) between mean irrigant volume collected at different flow
      rates. CONCLUSIONS: A greater volume was collected by increasing the flow rate of
      irrigant delivery for both EndoVac and INP. The INP needle could collect a
      greater volume of irrigant from the apical third compared with EndoVac at all 3
      different flow rates.

PMID- 29571909
TI  - Inhibition of SOX9 Promotes Inflammatory and Immune Responses of Dental Pulp.
AB  - INTRODUCTION: The process of pulpitis is characterized by extracellular matrix
      imbalance and inflammatory cell infiltration. As an essential transcription
      factor, sex-determining region Y-box 9 (SOX9) is significantly inhibited by tumor
      necrosis factor alpha in inflammatory joint diseases. The aim of this study was
      to explore the role of SOX9 in extracellular matrix balance, cytokine expression,
      and the immune response in dental pulp. METHODS: The expression of SOX9 in normal
      and inflamed pulp tissue/human dental pulp cells (HDPCs) was detected by
      immunohistochemistry, Western blot, and quantitative polymerase chain reaction
      (qPCR). SOX9 small interfering RNA was used to knock down SOX9 expression of
      dental cells in vitro; extracellular matrix imbalance was analyzed by qPCR,
      Western blot, and gelatin/collagen zymography, and the secretion of cytokines was
      scanned by antibody arrays. The immune response of THP-1 was investigated by cell
      migration assay, cell attachment assay, phagocytosis assay, and enzyme-linked
      immunosorbent assay. The interaction of SOX9 with target genes was explored by
      chromatin immunoprecipitation (ChIP). RESULTS: SOX9 was strongly expressed in
      normal dental pulp tissue and HDPCs and reduced in inflamed pulp. SOX9 knockdown
      could inhibit the production of type I collagen, stimulate the enzymatic
      activities of MMP2 and MMP13, and regulate the production of interleukin (IL) 8
      of HDPCs. SOX9 knockdown also effectively suppressed the differentiation and
      functional activities of THP-1. ChIP showed that the binding of the SOX9 protein
      with matrix metalloproteinase (MMP)-1, MMP-13, and IL-8 gene promoters was
      reduced after being treated with recombinant human tumor necrosis factor alpha.
      CONCLUSIONS: SOX9 was inhibited in inflamed dental pulp and may participate in
      the regulation of extracellular matrix balance, the inflammatory process, and the
      immune response.

PMID- 29571910
TI  - Guided Endodontic Access in Maxillary Molars Using Cone-beam Computed Tomography
      and Computer-aided Design/Computer-aided Manufacturing System: A Case Report.
AB  - The aim of this study was to describe a guided endodontic technique that
      facilitates access to root canals of molars presenting with pulp calcifications.
      A 61-year-old woman presented to our service with pain in the upper left molar
      region. The second and third left molars showed signs of apical periodontitis
      confirmed by the cone-beam computed tomographic (CBCT) scans brought to us by the
      patient at the initial appointment. Conventional endodontic treatment was
      discontinued given the difficulty in locating the root canals. Intraoral scanning
      and the CBCT scans were used to plan the access to the calcified canals by means
      of implant planning software. Guides were fabricated through rapid prototyping
      and allowed for the correct orientation of a cylindrical drill used to provide
      access through the calcifications. Second to that, the root canals were prepared
      with reciprocating endodontic instruments and rested for 2 weeks with intracanal
      medication. Subsequently, canals were packed with gutta-percha cones using the
      hydraulic compression technique. Permanent restorations of the access cavities
      were performed. By comparing the tomographic images, the authors observed a
      drastic reduction of the periapical lesions as well as the absence of pain
      symptoms after 3 months. This condition was maintained at the 1-year follow-up.
      The guided endodontic technique in maxillary molars was shown to be a fast, safe,
      and predictable therapy and can be regarded as an excellent option for the
      location of calcified root canals, avoiding failures in complex cases.

PMID- 29571911
TI  - A Novel Method for Characterizing Beam Hardening Artifacts in Cone-beam Computed
      Tomographic Images.
AB  - INTRODUCTION: The beam hardening (BH) artifact produced by root filling materials
      in cone-beam computed tomographic (CBCT) images is influenced by their radiologic
      K absorption edge values. The purpose of this study was to describe a novel
      technique to characterize BH artifacts in CBCT images produced by 3 root canal
      filling materials and to evaluate the effects of a zirconium (Zr)-based root
      filling material with a lower K edge (17.99 keV) on the production of BH
      artifacts. METHODS: The palatal root canals of 3 phantom model teeth were
      prepared and root filled with gutta-percha (GP), a Zr root filling material, and
      calcium hydroxide paste. Each phantom tooth was individually imaged using the CS
      9000 CBCT unit (Carestream, Atlanta, GA). The "light" and "dark" components of
      the BH artifacts were quantified separately using ImageJ software (National
      Institutes of Health, Bethesda, MD) in 3 regions of the root. Mixed-design
      analysis of variance was used to evaluate differences in the artifact area for
      the light and dark elements of the BH artifacts. RESULTS: A statistically
      significant difference in the area of the dark portion of the BH artifact was
      found between all fill materials and in all regions of the phantom tooth root (P
      < .05). GP generated a significantly greater dark but not light artifact area
      compared with Zr (P < .05). Moreover, statistically significant differences
      between the areas of both the light and dark artifacts were observed within all
      regions of the tooth root, with the greatest artifact being generated in the
      coronal third of the root (P < .001). CONCLUSIONS: Root canal filling materials
      with lower K edge material properties reduce BH artifacts along the entire length
      of the root canal and reduce the contribution of the dark artifact.

PMID- 29571912
TI  - Mechanical Properties of Glide Path Preparation Instruments with Different Pitch
      Lengths.
AB  - INTRODUCTION: This study compared the effects of pitch length on the torsional
      resistance and cyclic fatigue resistance of glide path preparation instruments.
      METHODS: G-File (G1 and G2; Micro-Mega, Besancon, France) and new generation G
      File (NG1 and NG2, Micro-Mega) instruments were compared to evaluate the effects
      of the shorter pitch of the latter (25% shorter than G-File). G1 and NG1 have a
      #12 tip size, whereas G2 and NG2 have a #17 tip size. All the files have the same
      taper of 3%. For comparing the torsional resistances (n = 15), the file was fixed
      at 4 mm from the tip, and the clockwise rotation at a constant rotational speed
      of 2 rpm was adjusted until the file fractured. The maximum torsional load and
      distortion angle at fracture were recorded. For comparing the cyclic fatigue
      resistances (n = 15), the files were freely rotated in a simulated canal (radius,
      3 mm; curvature, 90 degrees ) at a speed of 300 rpm in a dynamic mode. When the
      file fractured, the time elapsed was recorded using a chronometer. The number of
      cycles to failure was calculated by multiplying the total time to failure by the
      rotation rate. Fractured fragments were examined under the scanning electron
      microscope. RESULTS: The NG2 instruments had significantly higher fatigue
      resistance and torsional strength than the G2 instruments (P < .05) and showed
      approximately the same fatigue resistance as the G1. Scanning electron
      microscopic examinations revealed the typical appearances of 2 failure modes.
      CONCLUSIONS: A shorter pitch design increased cyclic fatigue resistance and
      torsional strength of the glide path instruments.

PMID- 29571913
TI  - Is the Use of Dexamethasone Effective in Controlling Pain Associated with
      Symptomatic Irreversible Pulpitis? A Systematic Review.
AB  - INTRODUCTION: Endodontic pain is a symptom of pulpal and/or periapical
      inflammation. One strategy for pain reduction is using medications, such as
      dexamethasone. A definitive protocol for preventing and controlling pain caused
      by irreversible pulpitis during endodontic treatment has not yet been
      established. This is a systematic review to answer the following question: is the
      use of dexamethasone effective in controlling pain associated with symptomatic
      irreversible pulpitis? METHODS: This study was registered in the PROSPERO
      database (CRD42017058704), and Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses statement recommendations were followed. MEDLINE, Scopus,
      ScienceDirect, Web of Science, Latin American Caribbean Health Sciences
      Literature, Cochrane Library, and Google Scholar databases were used in our
      research. No restrictions were applied to dates or language of publication. All
      records identified electronically were organized and evaluated by 2 independent
      authors, and, in case of doubt, a third author made the decision. The Cochrane
      Collaboration tool was used. The data were analyzed with RevMan 5 software (The
      Cochrane Collaboration, Copenhagen, Denmark), and data from eligible studies were
      dichotomous (with and without pain). RESULTS: A total of 4825 studies were
      identified. After screening, 523 studies were selected, and, after careful
      evaluation, only 5 articles remained. All meta-analyses revealed a global effect
      (P < .05, P < .05, and P < .05), which means that 4 mg dexamethasone helps
      relieve pain, sometimes for up to 8, 12, and 24 hours. CONCLUSIONS: The pain felt
      by patients diagnosed with symptomatic irreversible pulpitis may be alleviated by
      administering 4 mg dexamethasone either by mouth or through intraligamentary and
      mainly supraperiosteal injections into the root canal for up to 24 hours.

PMID- 29571914
TI  - Diagnostic Accuracy of 5 Dental Pulp Tests: A Systematic Review and Meta
      analysis.
AB  - INTRODUCTION: The aim of this systematic review was to investigate and compare
      the diagnostic accuracy including sensitivity, specificity, adjusted accuracy,
      adjusted positive predictive value (PPV), and adjusted negative predictive value
      (NPV) of cold pulp testing (CPT), heat pulp testing (HPT), electric pulp testing
      (EPT), laser Doppler flowmetry (LDF), and pulse oximetry (PO). METHODS: Three
      electronic databases were searched from January 1964 to December 2016. True
      positive, false-positive, true-negative, and false-negative values were extracted
      from data in each study. Sensitivity, specificity, adjusted accuracy, adjusted
      PPV, and adjusted NPV were calculated from those values, if not presented. A
      random effects model was used to calculate pooled estimates of sensitivity,
      specificity, adjusted accuracy, adjusted PPV, and adjusted NPV. RESULTS: A total
      of 125 articles were identified, and 28 studies were included for the final
      review. The pooled estimates of sensitivity for CPT, EPT, HPT, LDF, and PO were
      0.87, 0.72, 0.78, 0.98, and 0.97, respectively. Those of specificity were 0.84,
      0.93, 0.67, 0.95, and 0.95, respectively. Those of adjusted accuracy were 0.84,
      0.82, 0.72, 0.97, and 0.97, respectively. For adjusted PPV, they were 0.81, 0.89,
      0.62, 0.94, and 0.94, respectively, and for adjusted NPV, they were 0.87, 0.80,
      0.79, 1.00, and 0.99, respectively. CONCLUSIONS: LDF and PO were the most
      accurate diagnostic methods, and HPT was the least accurate diagnostic method.
      EPT showed high accuracy when testing vital teeth (specificity = 0.93) but low
      accuracy when assessing nonvital teeth (sensitivity = 0.72). CPT had moderate
      accuracy when evaluating vital (specificity = 0.84) and nonvital (sensitivity =
      0.87) teeth.

PMID- 29571915
TI  - Effect of Resin-based and Bioceramic Root Canal Sealers on Postoperative Pain: A
      Split-mouth Randomized Controlled Trial.
AB  - INTRODUCTION: The aim of this study was to compare the effect of resin-based and
      bioceramic root canal sealers on the occurrence and intensity of postoperative
      pain in patients with asymptomatic apical periodontitis (AAP). METHODS: Patients
      presenting with AAP in previously endodontically treated teeth were included in
      this split-mouth blinded randomized controlled trial. For each patient, 2 single
      rooted teeth were retreated and obturated using the warm vertical condensation
      technique and different obturation materials (ie, a gutta-percha point with resin
      based sealer and a bioceramic-coated gutta-percha point with bioceramic sealer).
      Treatment of 1 root canal was performed in a single visit. Postoperative pain was
      recorded by a visual analog scale (VAS) at 24 hours, 48 hours, 72 hours, and 7
      days after obturation. RESULTS: Of the 61 included patients, 57 individuals
      presenting 114 teeth completed the study. There was no statistically significant
      difference between the tested root canal sealers regarding postoperative pain at
      any time points assessed (P > .05). In total, 20 (35%) patients perceived pain.
      Only 1 patient reported severe pain. VAS scores of 80 and 70 were reported in the
      AH Plus (Dentsply Maillefer, Ballaigues, Switzerland) and Total Fill (FKG
      Dentaire SA, La Chaux-de-Fonds, Switzerland) groups, respectively. Pain intensity
      decreased about 2-fold in both groups at 48 hours after treatment. There were no
      reports of pain since 72 hours after obturation. The odds ratio for pain
      occurrence in the lower premolars was 7.2 (95% confidence interval, 1.708-30.352)
      compared with the upper front teeth. CONCLUSIONS: AH Plus and Total Fill perform
      similarly in terms of the occurrence and intensity of postoperative pain in teeth
      with AAP with no material extrusion beyond the apex.

PMID- 29571916
TI  - Safe of plasma exchange in acute renal failure secondary to vasculitis.

PMID- 29571917
TI  - Waldenstrom macroglobulinemia presenting as cryoglobulinemic type II
      membranoproliferative glomerulonephritis.

PMID- 29571918
TI  - Curcumin intake in hemodialysis patients.

PMID- 29571919
TI  - Age-dependent expression pattern in the mammalian brain of a novel, small peptide
      encoded in the 22q11.2 deletion syndrome region.
AB  - 22q11.2 deletion syndrome (22q11.2DS) carries increased risk for both physical
      and psychiatric symptoms, including a high risk for schizophrenia. Understanding
      the genetic elements within the deletion region therefore has the potential to
      unlock the mysteries of both diseases. While most of the protein-coding genes in
      this region have been characterized, novel elements, such as non-coding RNAs and
      small Open Reading Frames (sORFs) remain unstudied. We have identified a novel,
      highly-conserved mouse sORF in a region of the mouse genome that is orthologous
      to a portion of the 22q11.2 deletion. This region was previously associated with
      age-dependent synaptic plasticity abnormalities. We refer to it as the Plasticity
      Associated Neural Transcript Short, or Pants. In developing and aging mouse
      brain, Pants expression is strongest in hippocampus, especially in areas CA3 and
      CA2, throughout the dorsoventral axis. The Pants peptide is expressed throughout
      the hippocampus, with an age-dependent increase in stratum lucidum at 16 weeks of
      age. This expression pattern suggests a potential role for Pants in many
      hippocampal behaviors, as well as a potential role in the age-dependent
      neurologic deficits displayed by 22q11.2DS model mice and patients.

PMID- 29571920
TI  - Gastric and mesenteric ischemia due to double arterial occlusion.

PMID- 29571922
TI  - Can We Finally Dispense With Ketamine's Many Myths?

PMID- 29571921
TI  - Genetic diversity and symbiotic effectiveness of Phaseolus vulgaris-nodulating
      rhizobia in Kenya.
AB  - Phaseolus vulgaris (common bean) was introduced to Kenya several centuries ago
      but the rhizobia that nodulate it in the country remain poorly characterised. To
      address this gap in knowledge, 178 isolates recovered from the root nodules of P.
      vulgaris cultivated in Kenya were genotyped stepwise by the analysis of genomic
      DNA fingerprints, PCR-RFLP and 16S rRNA, atpD, recA and nodC gene sequences.
      Results indicated that P. vulgaris in Kenya is nodulated by at least six
      Rhizobium genospecies, with most of the isolates belonging to Rhizobium phaseoli
      and a possibly novel Rhizobium species. Infrequently, isolates belonged to
      Rhizobium paranaense, Rhizobium leucaenae, Rhizobium sophoriradicis and Rhizobium
      aegyptiacum. Despite considerable core-gene heterogeneity among the isolates,
      only four nodC gene alleles were observed indicating conservation within this
      gene. Testing of the capacity of the isolates to fix nitrogen (N2) in symbiosis
      with P. vulgaris revealed wide variations in effectiveness, with ten isolates
      comparable to Rhizobium tropici CIAT 899, a commercial inoculant strain for P.
      vulgaris. In addition to unveiling effective native rhizobial strains with
      potential as inoculants in Kenya, this study demonstrated that Kenyan soils
      harbour diverse P. vulgaris-nodulating rhizobia, some of which formed
      phylogenetic clusters distinct from known lineages. The native rhizobia differed
      by site, suggesting that field inoculation of P. vulgaris may need to be locally
      optimised.

PMID- 29571923
TI  - Prevalence and long-term monitoring of humoral immunity against adeno-associated
      virus in Duchenne Muscular Dystrophy patients.
AB  - Adeno-associated virus (AAV) vectors are promising candidates for gene therapy
      and have been explored as gene delivery vehicles in the treatment of Duchenne
      Muscular Dystrophy (DMD). Recent studies showed compelling evidence of
      therapeutic efficacy in large animal models following the intravenous delivery of
      AAV vectors expressing truncated forms of dystrophin. However, to translate these
      results to humans, careful assessment of the prevalence of anti-AAV neutralizing
      antibodies (NAbs) is needed, as presence of preexisting NABs to AAV in serum have
      been associated with a drastic diminution of vector transduction. Here we
      measured binding and neutralizing antibodies against AAV serotype 1, 2, and 8 in
      serum from children and young adults with DMD (n = 130). Results were compared
      with to age-matched healthy donors (HD, n = 113). Overall, approximately 54% of
      all subjects included in the study presented IgG to AAV2, 49% to AAV1, and 41% to
      AAV8. A mean of around 80% of IgG positive sera showed neutralizing activity with
      no statistical difference between DMD and HD. NAb titers for AAV2 were higher
      than AAV1, and AAV8 in both populations studied. Older DMD patients (13-24 years
      old) presented significantly lower anti-AAV8 IgG4 subclass. Anti-AAV antibodies
      were found to be decreased in DMD patients subjected to a 6-month course of
      corticosteroids and in subjects receiving a variety of immunosuppressive drugs
      including B cell targeting drugs. Longitudinal follow up of humoral responses to
      AAV over up to 6 years showed no change in antibody titers, suggesting that in
      this patient population, seroconversion is a rare event in humans.

PMID- 29571924
TI  - High red and processed meat consumption is associated with non-alcoholic fatty
      liver disease and insulin resistance.
AB  - BACKGROUND & AIMS: High red and processed meat consumption is related to type 2
      diabetes. In addition, cooking meat at high temperatures for a long duration
      forms heterocyclic amines (HCAs), which are related to oxidative stress. However,
      the association between meat consumption and non-alcoholic fatty liver disease
      (NAFLD) is yet to be thoroughly tested. Therefore, we aimed to test the
      association of meat type and cooking method with NAFLD and insulin resistance
      (IR). METHODS: This was a cross-sectional study in individuals who were 40-70
      years old and underwent screening colonoscopy between 2013 and 2015 in a single
      center in Israel. NAFLD and IR were evaluated by ultrasonography and homeostasis
      model assessment. Meat type and cooking method were measured by a food frequency
      questionnaire (FFQ) and a detailed meat questionnaire. Unhealthy cooking methods
      were considered as frying and grilling to a level of well done and very well
      done. Dietary HCA intake was calculated. RESULTS: A total of 789 individuals had
      a valid FFQ and 357 had a valid meat questionnaire. High consumption of total
      meat (portions/day above the median) (odds ratio [OR] 1.49; 95% CI 1.05-2.13; p =
      0.028; OR 1.63; 1.12-2.37; p = 0.011), red and/or processed meat (OR1.47; 95% CI
      1.04-2.09; p = 0.031; OR1.55; 1.07-2.23; p = 0.020) was independently associated
      with higher odds of NAFLD and IR, respectively, when adjusted for: body mass
      index, physical activity, smoking, alcohol, energy, saturated fat and cholesterol
      intake. High intake of meat cooked using unhealthy methods (OR1.92; 95% CI 1.12
      3.30; p = 0.018) and HCAs (OR2.22; 95% CI 1.28-3.86; p = 0.005) were
      independently associated with higher odds of IR. CONCLUSION: High consumption of
      red and/or processed meat is associated with both NAFLD and IR. High HCA intake
      is associated with IR. If confirmed in prospective studies, limiting the
      consumption of unhealthy meat types and improving preparation methods may be
      considered as part of NAFLD lifestyle treatment. LAY SUMMARY: High red and
      processed meat consumption is related to several diseases. In addition, cooking
      meat at high temperatures for a long duration forms heterocyclic amines, which
      have harmful health effects. Non-alcoholic fatty liver disease is a significant
      public health burden and its formation is strongly related to insulin resistance.
      In this study, both were found to be more frequent in people who consume
      relatively high quantities of red and processed meat. In addition, a high intake
      of heterocyclic amines was associated with insulin resistance.

PMID- 29571925
TI  - Mortality Risk and Hospital Admission after a Brief Resolved Unexplained Event.

PMID- 29571926
TI  - Fidget Spinner Ingestions in Children-A Problem that Spun Out of Nowhere.
AB  - The Consumer Product Safety Risk Management System's injury and potential injury
      database records 13 cases of fidget spinner ingestion since 2016. In addition to
      a database query, we report 3 additional cases of fidget spinner ingestion to
      describe patient presentations and subsequent management strategies.

PMID- 29571927
TI  - Implicit Physician Biases in Periviability Counseling.
AB  - OBJECTIVE: To assess whether neonatologists show implicit racial and/or
      socioeconomic biases and whether these are predictive of recommendations at
      extreme periviability. STUDY DESIGN: A nationwide survey using a clinical
      vignette of a woman in labor at 232/7 weeks of gestation asked physicians how
      likely they were to recommend intensive vs comfort care. Participants were
      randomized to 1 of 4 versions of the vignette in which racial and socioeconomic
      stimuli were varied, followed by 2 implicit association tests (IATs). RESULTS:
      IATs revealed implicit preferences favoring white (mean IAT score = 0.48, P <
      .001) and greater socioeconomic status (mean IAT score = 0.73, P < .001).
      Multivariable linear regression analysis showed that physicians with implicit
      bias toward greater socioeconomic status were more likely than those without bias
      to recommend comfort care when presented with a patient of high socioeconomic
      status (P = .037). No significant effect was seen for implicit racial bias.
      CONCLUSIONS: Building on previous demonstrations of unconscious racial and
      socioeconomic biases among physicians and their predictive validity, our results
      suggest that unconscious socioeconomic bias influences recommendations when
      counseling at the limits of viability. Physicians who display a negative
      socioeconomic bias are less likely to recommend resuscitation when counseling
      women of high socioeconomic status. The influence of implicit socioeconomic bias
      on recommendations at periviability may influence neonatal healthcare disparities
      and should be explored in future studies.

PMID- 29571928
TI  - Hemodynamic Changes During Rewarming Phase of Whole-Body Hypothermia Therapy in
      Neonates with Hypoxic-Ischemic Encephalopathy.
AB  - OBJECTIVE: To delineate the systemic and cerebral hemodynamic response to
      incremental increases in core temperature during the rewarming phase of
      therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY
      DESIGN: Continuous hemodynamic data, including heart rate (HR), mean arterial
      blood pressure (MBP), cardiac output by electrical velocimetry (COEV), arterial
      oxygen saturation, and renal (RrSO2) and cerebral (CrSO2) regional tissue oxygen
      saturation, were collected from 4 hours before the start of rewarming to 1 hour
      after the completion of rewarming. Serial echocardiography and transcranial
      Doppler were performed at 3 hours and 1 hour before the start of rewarming (T-3
      and T-1; "baseline") and at 2, 4, and 7 hours after the start of rewarming (T+2,
      T+4, and T+7; "rewarming") to determine Cardiac output by echocardiography
      (COecho), stroke volume, fractional shortening, and middle cerebral artery (MCA)
      flow velocity indices. Repeated-measures analysis of variance was used for
      statistical analysis. RESULTS: Twenty infants with HIE were enrolled (mean
      gestational age, 38.8 +/- 2 weeks; mean birth weight, 3346 +/- 695 g). During
      rewarming, HR, COecho, and COEV increased from baseline to T+7, and MBP
      decreased. Despite an increase in fractional shortening, stroke volume remained
      unchanged. RrSO2 increased, and renal fractional oxygen extraction (FOE)
      decreased. MCA peak systolic flow velocity increased. There were no changes in
      CrSO2 or cerebral FOE. CONCLUSIONS: In neonates with HIE, CO significantly
      increases throughout rewarming. This is due to an increase in HR rather than
      stroke volume and is associated with an increase in renal blood flow. The lack of
      change in cerebral tissue oxygen saturation and extraction, in conjunction with
      an increase in MCA peak systolic velocity, suggests that cerebral flow metabolism
      coupling remained intact during rewarming.

PMID- 29571929
TI  - Pediatric Tonsil Cancer: A National and Institutional Perspective.
AB  - OBJECTIVE: To evaluate childhood and adolescent tonsil cancer incidence and to
      identify the clinical characteristics indicative of those patients who would
      benefit from urgent operative intervention. STUDY DESIGN: The Surveillance,
      Epidemiology and End Results 18 database, inclusive of national cancer statistics
      from 1973 to 2013, provided quantitative tonsil cancer incidence data. An
      institutional retrospective chart review of pediatric patients diagnosed with
      tonsil malignancy from January 2013 to January 2017 identified supplementary
      qualitative clinical presentation information. RESULTS: The Surveillance,
      Epidemiology and End Results 18 database included 138 pediatric patients with
      tonsil cancer with an age-adjusted incidence rate of 0.021/100 000 patients per
      year. The majority of cases were unilateral (79.7%), and there was both a male
      and Caucasian predominance. Non-Hodgkin lymphoma (84.1%) was the most common
      malignancy, of which Burkitt lymphoma (31.1%), diffuse large B-cell lymphoma
      (26.8%), and follicular lymphoma (10.1%) were the most common subtypes. Five
      tonsillar malignancy patients were identified upon institutional chart review.
      The majority likewise had non-Hodgkin lymphoma and all shared a history of rapid
      tonsillar enlargement over <=12 weeks. Significant tonsillar asymmetry was
      present in 4 patients. Four patients additionally exhibited prominent cervical
      lymphadenopathy. CONCLUSIONS: Pediatric tonsil cancer is rare, with non-Hodgkin
      lymphoma accounting for the majority of pediatric tonsillar malignancies. A high
      index of suspicion is appropriate in children who present with relatively rapid
      tonsil enlargement, tonsillar asymmetry characterized by a difference in
      tonsillar size of >=2 degrees on the Brodsky scale, or concurrent prominent
      cervical lymphadenopathy.

PMID- 29571931
TI  - Effectiveness of Pediatric Asthma Pathways for Hospitalized Children: A
      Multicenter, National Analysis.
AB  - OBJECTIVE: To determine if clinical pathways affect care and outcomes for
      children hospitalized with asthma using a multicenter study. STUDY DESIGN: This
      was a retrospective, multicenter cohort study using an administrative database,
      the Pediatric Health Information System. We evaluated the impact of inpatient
      pediatric asthma pathways on children age 2-17 years admitted for asthma from
      2006 to 2015 in 42 children's hospitals. Date of pathway implementation for each
      hospital was collected via survey. Using generalized estimating equations with an
      interrupted time series approach (to account for secular trends), we determined
      the association of pathway implementation with length of stay (LOS), 30-day
      readmission, chest radiograph utilization, ipratropium administration >24 hours,
      and administration of bronchodilators, systemic steroids, and antibiotics. All
      analyses were risk-adjusted for patient and hospital characteristics. RESULTS:
      Clinical pathway implementation was associated with an 8.8% decrease in LOS (95%
      CI 6.7%-10.9%), 3.1% decrease in hospital costs (95% CI 1.9%-4.3%), increased
      odds of bronchodilator administration (OR 1.53[1.21-1.95]) and decreased odds of
      antibiotic administration (OR 0.93[0.87-0.99]) (n = 189 331). We found no
      associations between pathway implementation and systemic steroid administration,
      ipratropium administration for >24 hours, chest radiograph utilization, or 30-day
      readmission. CONCLUSIONS: Clinical pathways can decrease LOS, costs, and
      unnecessary antibiotic use without increasing rates of readmissions, leading to
      higher value care.

PMID- 29571932
TI  - Optimal Target Range of Closed-Loop Inspired Oxygen Support in Preterm Infants: A
      Randomized Cross-Over Study.
AB  - OBJECTIVE: To investigate the effect of different pulse oximetry (SpO2) target
      range settings during automated fraction of inspired oxygen control (A-FiO2) on
      time spent within a clinically set SpO2 alarm range in oxygen-dependent infants
      on noninvasive respiratory support. STUDY DESIGN: Forty-one preterm infants
      (gestational age [median] 26 weeks, age [median] 21 days) on FiO2 >0.21 receiving
      noninvasive respiratory support were subjected to A-FiO2 using 3 SpO2 target
      ranges (86%-94%, 88%-92%, or 89%-91%) in random order for 24 hours each. Before
      switching to the next target range, SpO2 was manually controlled for 24 hours
      (washout period). The primary outcome was the time spent within the clinically
      set alarm limits of 86%-94%. RESULTS: The percent time within the 86%-94% SpO2
      alarm range was similar for all 3 A-FiO2 target ranges (74%). Time spent in
      hyperoxemia was not significantly different between target ranges. However, the
      time spent in severe hypoxemia (SpO2 <80%) was significantly reduced during the
      narrowed target ranges of A-FiO2 (88%-92%; 1.9%, 89%-91%; 1.7%) compared with the
      wide target range (86%-94%; 3.4%, P < .001). There were no differences between
      the 88%-92% and 89-91% target range. CONCLUSIONS: Narrowing the target range of A
      FiO2 to the desired median +/-2% is effective in reducing the time spent in
      hypoxemia, without increasing the risk of hyperoxemia. TRIAL REGISTRATION:
      www.trialregister.nl: NTR4368.

PMID- 29571933
TI  - Disparities in Access to Healthcare Transition Services for Adolescents with Down
      Syndrome.
AB  - OBJECTIVE: To compare healthcare transition planning in adolescents with Down
      syndrome with adolescents with other special healthcare needs. STUDY DESIGN: Data
      were drawn from the 2009-2010 National Survey of Children with Special Health
      Care Needs, a nationally representative sample with 17 114 adolescents aged 12-17
      years. Parents were asked whether providers and the study child had discussed
      shifting to an adult provider, changing healthcare needs, maintaining health
      insurance coverage, and taking responsibility for self-care. The transition core
      outcome was a composite measure based on the results of these 4 questions.
      Multivariable logistic regression determined the association between Down
      syndrome and the transition core outcome as well as each of the 4 individual
      component measures. RESULTS: Although 40% of adolescents with other special
      healthcare needs met the transition core outcome, 11.0% of adolescents with Down
      syndrome met this outcome. Adolescents with Down syndrome were less likely to be
      encouraged to take responsibility for their health (32.2% vs 78.4%). After
      adjustment for demographic, socioeconomic, and health-related factors,
      adolescents with Down syndrome had 4 times the odds of not meeting the transition
      core outcome. For the component measures, Down syndrome adolescents had 4 times
      the odds of not being encouraged to take responsibility for self-care. Medical
      home access increased the odds of transition preparation. CONCLUSIONS:
      Adolescents with Down syndrome experience disparities in access to transition
      services. Provider goals for adolescents with Down syndrome should encourage as
      much independence as possible in their personal care and social lives.

PMID- 29571930
TI  - HABIT, a Randomized Feasibility Trial to Increase Hydroxyurea Adherence, Suggests
      Improved Health-Related Quality of Life in Youths with Sickle Cell Disease.
AB  - OBJECTIVES: To examine the effect of a community health worker (CHW)
      intervention, augmented by tailored text messages, on adherence to hydroxyurea
      therapy in youths with sickle cell disease, as well as on generic and disease
      specific health-related quality of life (HrQL) and youth-parent self-management
      responsibility concordance. STUDY DESIGN: We conducted a 2-site randomized
      controlled feasibility study (Hydroxyurea Adherence for Personal Best in Sickle
      Cell Treatment [HABIT]) with 2:1 intervention allocation. Youths and parents
      participated as dyads. Intervention dyads received CHW visits and text message
      reminders. Data were analyzed using descriptive statistics, the Wilcoxon signed
      rank test, and growth models adjusting for group assignment, time, and multiple
      comparisons. Changes in outcomes from 0 to 6 months were compared with their
      respective minimal clinically important differences. RESULTS: A total of 28 dyads
      (mean age of youths, 14.3 +/- 2.6 years; 50% Hispanic) participated (18 in the
      intervention group, 10 in the control group), with 10.7% attrition. Accounting
      for group assignment, time, and multiple comparisons, at 6 months intervention
      youths reported improved generic HrQL total score (9.8 points; 95% CI, 0.4-19.2)
      and Emotions subscale score (15.0 points; 95% CI, 1.6-28.4); improved disease
      specific subscale scores for Worry I (30.0 points; 95% CI, 8.5-51.5), Emotions
      (37.0 points, 95% CI, 9.4-64.5), and Communication I (17.8 points; 95% CI, 0.5
      35.1); and 3-month dyad self-management responsibility concordance (3.5 points;
      95% CI, -0.2 to 7.1). There were no differences in parent proxy-reported HrQL
      measures at 6 months. CONCLUSIONS: These findings add to research examining
      effects of behavioral interventions on HrQL outcomes in youths with sickle cell
      disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02029742.

PMID- 29571934
TI  - Multi-institutional evaluation of end-to-end protocol for IMRT/VMAT treatment
      chains utilizing conventional linacs.
AB  - We conducted a multi-institutional assessment of a recently developed end-to-end
      monthly quality assurance (QA) protocol for external beam radiation therapy
      treatment chains. This protocol validates the entire treatment chain against a
      baseline to detect the presence of complex errors not easily found in standard
      component-based QA methods. Participating physicists from 3 institutions ran the
      end-to-end protocol on treatment chains that include Imaging and Radiation
      Oncology Core (IROC)-credentialed linacs. Results were analyzed in the form of
      American Association of Physicists in Medicine (AAPM) Task Group (TG)-119 so that
      they may be referenced by future test participants. Optically stimulated
      luminescent dosimeter (OSLD), EBT3 radiochromic film, and A1SL ion chamber
      readings were accumulated across 10 test runs. Confidence limits were calculated
      to determine where 95% of measurements should fall. From calculated confidence
      limits, 95% of measurements should be within 5% error for OSLDs, 4% error for
      ionization chambers, and 4% error for (96% relative gamma pass rate) radiochromic
      film at 3% agreement/3 mm distance to agreement. Data were separated by
      institution, model of linac, and treatment protocol (intensity-modulated
      radiation therapy [IMRT] vs volumetric modulated arc therapy [VMAT]). A total of
      97% of OSLDs, 98% of ion chambers, and 93% of films were within the confidence
      limits; measurements were found outside these limits by a maximum of 4%, < 1%,
      and < 1%, respectively. Data were consistent despite institutional differences in
      OSLD reading equipment and radiochromic film calibration techniques. Results from
      this test may be used by clinics for data comparison. Areas of improvement were
      identified in the end-to-end protocol that can be implemented in an updated
      version. The consistency of our data demonstrates the reproducibility and ease-of
      use of such tests and suggests a potential role for their use in broad end-to-end
      QA initiatives.

PMID- 29571935
TI  - Normal Tissue Dose Constraints for Multiple Lung Stereotactic Radiotherapy
      Treatments.

PMID- 29571936
TI  - Early Results of Extreme Hypofractionation Using Stereotactic Body Radiation
      Therapy for High-risk, Very High-risk and Node-positive Prostate Cancer.
AB  - AIMS: Stereotactic body radiotherapy (SBRT) in low- and intermediate-risk
      prostate cancer has shown encouraging results. However, its use in high-risk
      patients is limited due to lack of data regarding adequate radiotherapy dose,
      need for pelvic nodal treatment and androgen deprivation therapy. Herein we
      report our experience of SBRT in this subgroup. MATERIALS AND METHODS: Analysis
      of a prospectively maintained database of 68 consecutive patients of the National
      Comprehensive Cancer Network (NCCN) high-risk, very high-risk and node-positive
      adenocarcinoma prostate treated with SBRT was undertaken. All patients were
      treated with rotational intensity-modulated radiotherapy with daily image
      guidance. The dose delivered to the prostate and gross node was 35-37.5 Gy in 5
      alternate day fractions. Node-positive patients received 25 Gy to pelvic nodal
      regions until the common iliac nodes. Treatment was delivered in 7-10 days. All
      patients received long-term androgen deprivation therapy (79% medical and 21%
      surgical). RESULTS: Most patients (65%) had a Gleason score >= 8. The median
      prostate-specific antigen was 42. Twenty patients were high risk (30%), 11 (16%)
      very high risk and 37 (54%) node positive. No acute Radiation Therapy Oncology
      Group grade >= 3 genitourinary or gastrointestinal toxicity was noted. Acute
      grade 2 genitourinary and gastrointestinal toxicity were 12% and 3%,
      respectively. Late grade 3 genitourinary and gastrointestinal toxicity was 3% and
      0%, respectively. There was no increase in acute or late gastrointestinal
      toxicity with prophylactic pelvic nodal radiotherapy. Prior transurethral
      resection of prostate (n = 11) did not increase toxicity. At a median follow-up
      of 18 months, 97% patients were alive and 94% were biochemically controlled.
      CONCLUSION: SBRT is safe in the treatment of high-risk, very high-risk and node
      positive prostate cancer, even with prophylactic pelvic radiotherapy or prior
      transurethral resection of prostate. Longer follow-up is required to determine
      efficacy.

PMID- 29571938
TI  - Trends in childhood height and weight, and socioeconomic inequalities.

PMID- 29571937
TI  - Socioeconomic inequalities in childhood and adolescent body-mass index, weight,
      and height from 1953 to 2015: an analysis of four longitudinal, observational,
      British birth cohort studies.
AB  - BACKGROUND: Socioeconomic inequalities in childhood body-mass index (BMI) have
      been documented in high-income countries; however, uncertainty exists with regard
      to how they have changed over time, how inequalities in the composite parts (ie,
      weight and height) of BMI have changed, and whether inequalities differ in
      magnitude across the outcome distribution. Therefore, we aimed to investigate how
      socioeconomic inequalities in childhood and adolescent weight, height, and BMI
      have changed over time in Britain. METHODS: We used data from four British
      longitudinal, observational, birth cohort studies: the 1946 Medical Research
      Council National Survey of Health and Development (1946 NSHD), 1958 National
      Child Development Study (1958 NCDS), 1970 British Cohort Study (1970 BCS), and
      2001 Millennium Cohort Study (2001 MCS). BMI (kg/m2) was derived in each study
      from measured weight and height. Childhood socioeconomic position was indicated
      by the father's occupational social class, measured at the ages of 10-11 years.
      We examined associations between childhood socioeconomic position and
      anthropometric outcomes at age 7 years, 11 years, and 15 years to assess
      socioeconomic inequalities in each cohort using gender-adjusted linear regression
      models. We also used multilevel models to examine whether these inequalities
      widened or narrowed from childhood to adolescence, and quantile regression was
      used to examine whether the magnitude of inequalities differed across the outcome
      distribution. FINDINGS: In England, Scotland, and Wales, 5362 singleton births
      were enrolled in 1946, 17 202 in 1958, 17 290 in 1970, and 16 404 in 2001. Low
      socioeconomic position was associated with lower weight at childhood and
      adolescent in the earlier-born cohorts (1946-70), but with higher weight in the
      2001 MCS cohort. Weight disparities became larger from childhood to adolescence
      in the 2001 MCS but not the earlier-born cohorts (pinteraction=0.001). Low
      socioeconomic position was also associated with shorter height in all cohorts,
      yet the absolute magnitude of this difference narrowed across generations. These
      disparities widened with age in the 2001 MCS (pinteraction=0.002) but not in the
      earlier-born cohorts. There was little inequality in childhood BMI in the 1946-70
      cohorts, whereas inequalities were present in the 2001 cohort and widened from
      childhood to adolescence in the 1958-2001 cohorts (pinteraction<0.05 in the later
      three cohorts but not the 1946 NSHD). BMI and weight disparities were larger in
      the 2001 cohort than in the earlier-born cohorts, and systematically larger at
      higher quantiles-eg, in the 2001 MCS at age 11 years, a difference of 0.98 kg/m2
      (95% CI 0.63-1.33) in the 50th BMI percentile and 2.54 kg/m2 (1.85-3.22)
      difference at the 90th BMI percentile were observed. INTERPRETATION: Over the
      studied period (1953-2015), socioeconomic-associated inequalities in weight
      reversed and those in height narrowed, whereas differences in BMI and obesity
      emerged and widened. These substantial changes highlight the impact of societal
      changes on child and adolescent growth and the insufficiency of previous policies
      in preventing obesity and its socioeconomic inequality. As such, new and
      effective policies are required to reduce BMI inequalities in childhood and
      adolescence. FUNDING: UK Economic and Social Research Council, Medical Research
      Council, and Academy of Medical Sciences/the Wellcome Trust.

PMID- 29571939
TI  - Modification of apparent intracerebral hematoma volume on T2*-weighted images
      during normobaric oxygen therapy may contribute to false diagnosis.
AB  - It was previously reported that normobaric oxygen therapy (NBO) significantly
      affected T2*-weighted imaging in a mouse model of intracerebral hemorrhage (ICH).
      However, it is unclear whether a similar phenomenon exists in large volume ICH as
      seen in human pathology. We investigated the effects of NBO on T2*-weighted
      images in a pig model of ICH. Our data show that NBO makes disappear a peripheral
      crown of the hematoma, which in turn decreases the apparent volume of ICH by 18%.
      We hypothesized that this result could be translated to ICH in human, and
      subsequently could lead to inaccurate diagnostic.

PMID- 29571940
TI  - Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in
      rats.
AB  - Ultrafiltration failure is a major complication of long-term peritoneal dialysis,
      resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure
      to high glucose dialysate is the major contributor of ultrafiltration failure,
      for which there is no effective treatment. Overactivation of several signaling
      pathways, including transforming growth factor-beta1 (TGF-beta1) and platelet
      derived growth factor (PDGF) pathways, contribute to the development of
      peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling
      pathways might be a potential novel method of treating peritoneal fibrosis.
      Previously, we showed that core fucosylation, an important posttranslational
      modification of the TGF-beta1 receptors, can regulate the activation of TGF-beta1
      signaling in renal interstitial fibrosis. However, it remains unclear whether
      core fucosylation affects the progression of peritoneal fibrosis. Herein, we show
      that core fucosylation was enriched in the peritoneal membrane of rats
      accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking
      core fucosylation dramatically attenuated peritoneal fibrosis in the rat model
      achieved by simultaneously inactivating the TGF-beta1 and PDGF signaling
      pathways. Next the protective effects of blocking core fucosylation and imatinib
      (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and
      found to exhibit a greater inhibitory effect over imatinib alone, suggesting that
      blocking activation of multiple signaling pathways may have superior inhibitory
      effects on the development of peritoneal fibrosis. Thus, core fucosylation is
      essential for the development of peritoneal fibrosis by regulating the activation
      of multiple signaling pathways. This may be a potential novel target for drug
      development to treat peritoneal fibrosis.

PMID- 29571941
TI  - Suppression of Epithelial Autophagy Compromises the Homeostasis of Sweat Glands
      during Aging.

PMID- 29571942
TI  - A CARD10-Dependent Tonic Signalosome Activates MALT1 Paracaspase and Regulates IL
      17/TNF-alpha-Driven Keratinocyte Inflammation.

PMID- 29571943
TI  - Sensitivity of Transglutaminase 3 in the IgA Aggregates in Dermatitis
      Herpetiformis Skin to Potassium Iodide.

PMID- 29571944
TI  - IL-17-Mediated Immunity Controls Skin Infection and T Helper 1 Response during
      Experimental Microsporum canis Dermatophytosis.
AB  - Despite worldwide prevalence of superficial mycoses, the immune response in
      dermatophytosis has scarcely been investigated. In this study, we developed a
      model of superficial skin infection in C57BL/6 mice with Microsporum canis, a
      highly prevalent human pathogen. This model mimics mild inflammatory human
      dermatophytosis, characterized by neutrophil recruitment and fungal invasion
      limited to the epidermis and exhibits the establishment of a specific T helper
      type 17 immune response during infection. By using IL-17RA- or IL-17A/F-deficient
      mice we showed that, in the absence of a functional IL-17 pathway, M. canis
      extensively colonizes the epidermis and promotes an exaggerated skin inflammation
      and a shift to an IFN-gamma-mediated (T helper type 1) response. IL-17 signaling
      was not involved in neutrophil influx to skin or fungal invasion to deeper
      tissues. Finally, this study shows that skin langerin-expressing cells contribute
      to the antifungal T helper type 17 response in vivo. In conclusion, these data
      directly show a dual function of IL-17 cytokines in dermatophytosis by
      controlling superficial infection and down-modulating a T helper type 1
      antifungal response.

PMID- 29571945
TI  - Trophoblast CD200 expression in successful human pregancies and missed abortions.
AB  - Presence of the CD200 immune check-point inhibitor at the feto-maternal interface
      is linked to prevention of spontaneous abortion in mice and humans. In human
      missed abortions (MA), absence of Th17-driven inflammation has been attributed to
      expression of villus trophoblast CD200 quantified using immunohistochemistry.
      While rapid aneuploidy (QF-PCR) testing linked low CD200 to pregnancy failure,
      data showing normal VT CD200 in first trimester normal pregnancy and in abortion
      of chromosomally abnormal embryos has not been demonstrated. The present report
      shows normal CD200 in a 7 week gestation termination with normal male QF-PCR and
      in a 10 week male trisomy 18 MA.

PMID- 29571947
TI  - Nilotinib in locally advanced pigmented villonodular synovitis: challenges of a
      new targeted therapy.

PMID- 29571946
TI  - Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre,
      open-label, single-arm, phase 2 trial.
AB  - BACKGROUND: Pigmented villonodular synovitis (alternatively known as diffuse-type
      giant cell tumour) is a rare, locally aggressive tumour driven by a specific
      translocation resulting in the overexpression of colony-stimulating factor 1
      (CSF1). CSF1 receptor (CSF1R) inhibitors (ie, tyrosine kinase inhibitors and
      antibodies) induce a response in patients with pigmented villonodular synovitis.
      We investigated the safety and efficacy of a CSF1R tyrosine kinase inhibitor,
      nilotinib, in patients with locally advanced non-resectable pigmented
      villonodular synovitis. METHODS: In this phase 2, open-label, single-arm study,
      we enrolled patients from 11 cancer centres of hospitals in four countries
      (France, Netherlands, Italy, and Australia). Eligible patients were aged at least
      18 years with a WHO performance status of 2 or less, and histologically confirmed
      progressive or relapsing pigmented villonodular synovitis that was inoperable, or
      resectable only with mutilating surgery. Patients received oral nilotinib (400 mg
      twice per day) until disease progression, unacceptable toxicity, or completion of
      1 year of treatment. The primary endpoint was the proportion of patients who were
      progression free at 12 weeks, which was centrally assessed according to Response
      Evaluation Criteria in Solid Tumors version 1.1. Analyses were by modified
      intention to treat (ie, all patients with no major protocol violations who were
      treated with nilotinib for at least 3 weeks were included). All participants who
      received at least one dose of study drug were included in the safety analyses.
      This study is registered with ClinicalTrials.gov, number NCT01261429, and the
      results presented here are the final analysis of the trial. FINDINGS: Between Dec
      15, 2010, and Sept 28, 2012, we enrolled 56 patients with pigmented villonodular
      synovitis and treated them with nilotinib. Five (9%) patients discontinued study
      treatment before week 12; therefore, 51 patients were evaluable for the primary
      endpoint at 12 weeks. The estimated proportion of patients who were progression
      free at 12 weeks was 92.6% (95% credible interval 84.3-97.9). 54 (96%) of 56
      patients had a treatment-related adverse event. Six (11%) of 56 patients had at
      least one grade 3 treatment-related adverse event (headache, dizziness, and
      hepatic disorders [n=1], pruritus and toxidermia [n=1], diarrhoea [n=1],
      increased gamma-glutamyl transferase concentration [n=1], anorexia [n=1], and
      increased headache [n=1]). No grade 4 or 5 adverse events were reported. One
      patient had a treatment-related serious adverse event (toxidermia) and two
      patients had serious adverse events not considered to be related to the study
      drug (borderline ovarian tumour [n=1] and pilonidal cyst excision [n=1]).
      INTERPRETATION: More than 90% of patients with locally advanced unresectable
      progressive pigmented villonodular synovitis achieved disease control with 12
      weeks of nilotinib treatment. These results indicate that CSF1R tyrosine kinase
      inhibitors have anti-tumour activity with manageable toxicity in patients with
      inoperable progressive pigmented villonodular synovitis. Randomised trials
      investigating the efficacy of nilotinib for patients with unresectable pigmented
      villonodular synovitis are warranted. FUNDING: Novartis, Institut National du
      Cancer, EuroSARC, French National Cancer Institute, General Directorate of Care
      Supply, Lyon Research Innovation for Cancer, L'Agence nationale de la recherche,
      Laboratory of Excellence, Fondation ARC pour la recherche sur le cancer, Ligue
      contre le Cancer (comite de l'Ain), Info Sarcomes, and Association DAM'S.

PMID- 29571948
TI  - Neurological outcome at 6 and 12 months corrected age in hospitalised late
      preterm infants -a prospective study.
AB  - Late preterm infants (34-0/7 to 36-6/7 weeks" gestation) account for 10-20% of
      NICU admissions and are at increased risk for morbidity and mortality. Although
      they are prone to developmental delays, reports on neurological outcome during
      the first 2 years of life are scarce. The aim of the study was to assess
      neurological/neuromotor outcome in high risk late preterm infants at 6 and 12
      months corrected age and the change in neurological scores over time, and to
      identify factors associated with the neurological outcome. The Hammersmith Infant
      Neurological Examination was performed in a cohort of 157 late preterm infants
      admitted in the NICU. The infants were examined at 6 and 12 months corrected age
      respectively and scored with the optimality score system including 26 items
      assessing cranial nerve function, posture, movements, tone and reflexes. Also
      parents reported neurological milestones in the follow up visit. Infants at 6
      months had a global score of 59 (47-76) and optimal scores achieved in 25.4%. At
      12 months they had a global score of 70 (58-78) and achieved optimal scores in
      63.2%. The subscores of posture, tone and reflexes gradually increased from 6 to
      12 months corrected age. Being born small for gestational age was the only factor
      that adversely influenced HINE score at 6 and 12 months. At 12 months 58.5%
      achieved independent walking. High risk late preterm infants have suboptimal HINE
      scores at 6 and 12 months of age, suggesting a need for closer follow up and
      early intervention programs.

PMID- 29571949
TI  - Hypoxia-induced HMGB1 expression of HCC promotes tumor invasiveness and
      metastasis via regulating macrophage-derived IL-6.
AB  - Hypoxia is associated with the progression of hepatocellular carcinoma through
      promotion of spontaneous metastasis but the mechanism remains unclear. Here, we
      hypothesis that tumor cell-derived HMGB1 orchestrates macrophages infiltration
      and promotes metastasis of HCC via enhancing macrophage-secreted IL-6 under
      hypoxia. HMGB1 expression was robustly exacerbated in tumors of HCC patients with
      PVTT. Meanwhile, hypoxia exposure gave rise to HMGB1 expression in hepatoma cells
      of human and mouse in a HIF-1alpha-dependent manner and subsequently induced the
      infiltration and reprogramming of macrophages to augment the expression of Il-6.
      Further study demonstrated macrophage-derived IL-6 enhanced the invasiveness and
      metastasis of murine HCC cells. Therefore, our study provides a novel
      understanding of the relationship between tumor cells and tumor associated
      macrophages (TAMs) in the context of hypoxia.

PMID- 29571950
TI  - Aurora A regulates the architecture of the Golgi apparatus.
AB  - The Golgi apparatus plays roles in cell polarity, directional cell migration, and
      bipolar spindle assembly, as well as the secretary pathway. In addition, recent
      studies have suggested the Golgi-dependent control of mitotic entry. We studied
      the role of the centrosomal kinase Aurora A in maintaining the Golgi apparatus.
      Knockdown of Aurora A resulted in Golgi dispersal during interphase. Golgi
      dispersal was also induced by a selective Aurora A inhibitor, MLN8237.
      Conversely, overexpression of Aurora A led to tightly packed Golgi apparatus
      during interphase. Knockdown or inhibition of Aurora A had little or no effect on
      Golgi vesiculation during mitosis. By synchronizing cell division, we studied
      whether mitosis was required to induce Golgi dispersal during interphase. Aurora
      A inhibition induced aberrant mitotic spindle and Golgi dispersal only after
      mitosis. However, the cells treated with the inhibitor MLN8237 at earlier cell
      cycle stages (wherein the cells remained undivided) had a normal Golgi
      architecture. Knockdown or inhibition of Aurora A also led to aberrant integrity
      of centrosome and Golgi apparatus during interphase. These results suggest that
      Aurora A activity is involved in the maintenance of Golgi architecture and the
      relationship between the Golgi apparatus and centrosome.

PMID- 29571951
TI  - [Benign aggressive vascular anomalies in children].
AB  - Superficial vascular anomalies constitute a large group of malformative and
      tumoral conditions developed from all types of vessels. Vascular tumors are the
      result of cellular hyperplasia, whereas vascular malformations (VMs) are
      constituted of dysplastic vessels. The classification from International Society
      for the Study of Vascular Anomalies (ISSVA) is based on this pathogenic
      difference. The most common vascular tumor is infantile hemangioma, which
      treatment, when necessary, is propranolol. Congenital hemangiomas and tumors that
      might be complicated with Kasabach-Merritt phenomenon, i.e. deep
      thrombocytopenia, are much rarer. Management of Kasabach-Merritt phenomenon is
      now largely based on sirolimus. Low-flow VMs include capillary, venous and
      lymphatic malformations; arteriovenous malformations are high-flow malformations.
      These different types of VMs might be combined. Currently, there is an increasing
      work in delineating the different entities based on molecular findings. Treatment
      of VMs depends on the impairment linked to them, and is decided case by case, in
      pluridisciplinary consultations. Interventional treatments, especially surgery
      and sclerotherapy, are usually partially efficient, and management of patients
      with VMs increasingly involves medical drugs. First-line treatment of coagulation
      disorders associated with venous malformations is based on low molecular weight
      heparin; sirolimus seems efficient in hemorrhagic complications refractory to
      usual treatment. Sirolimus is about to become the standard treatment in painful
      inflammatory manifestations of mixed and/or complicated lymphatic malformations.

PMID- 29571952
TI  - An Evaluation of Trends in Patient and Public Awareness of IR.
AB  - PURPOSE: To evaluate patient and public awareness of interventional radiology
      (IR). MATERIALS AND METHODS: This single-center study prospectively administered
      voluntary paper surveys to 80 patients in an academic hospital radiology waiting
      room. Separate, Internet-based surveys were administered to the general public.
      Additionally, Internet metadata were used to evaluate relative search engine
      activity and IR-related news coverage compared with similar procedural
      specialties. RESULTS: 65% of radiology department outpatients had no prior
      knowledge of IR. Of the general population surveyed, 72% could not identify an
      interventional radiologist as a physician. Relative annual IR-related Google
      search volumes peaked in 2004 and were at their nadir in 2011. After normalizing
      for number of practicing physicians, IR was the subject of substantially fewer
      Google searches than similar specialties (15.9% of urology volumes, 27.9% of
      cardiology volumes, and 39.0% of vascular surgery volumes). Between 2006 and
      2016, IR had a similar rate of annual increase in the volume of Internet news
      results as similar medical specialties, although the volumes reached by IR in
      2016 were obtained by more established fields, such as cardiology, in 2011.
      CONCLUSIONS: These data provide metrics of current and historical awareness
      trends in IR, which demonstrate low patient and public awareness. The findings of
      this study may help guide future efforts to promote patient and public awareness
      of IR.

PMID- 29571953
TI  - Reversing the effects of 2% Lidocaine: A randomized controlled clinical trial.
AB  - OBJECTIVES: Prolonged soft tissue anesthesia following a dental appointment is a
      complaint that is frequently reported by patients. Soft tissue anesthesia
      generally exceeds the duration of pulpal anesthesia by a few hours. This can lead
      to difficulties with smiling, drinking, speaking and lip/cheek biting following
      dental appointments. Phentolamine Mesylate (PM) is a pharmacological agent
      capable of reducing the duration of soft tissue anesthesia following dental
      treatments. Many clinical trials supporting its efficacy have used sham
      injections compared to injections with PM. The present study aims to evaluate the
      effect of PM on the duration of soft tissue anesthesia compared to a control
      injection of saline water. METHODS: This randomized controlled trial recruited 40
      participants above 18 years of age. Following an inferior alveolar nerve block
      using 1.8 ml of Lidocaine 2%, 1:100 000 epinephrine, participants were randomized
      into one of 2 groups. The test group received an injection of 0.4 mg PM
      (OraVerse). Participants in the control group received an injection of sterile
      saline water. Participants were trained in self-assessing their anesthesia, which
      they did until return to normal sensation. RESULTS: Thirty-six participants
      completed the study. PM significantly reduced the duration of soft tissue
      anesthesia in the lower lip (104 vs 170 min, p = .001), and tongue (83 vs 134
      min, p = .004) compared to the control injection. No serious adverse events were
      encountered. The only adverse events observed were post-operative pain and
      discomfort. CONCLUSIONS: Phentolamine Mesylate hastens the return to normal soft
      tissue sensation and function by approximately one hour compared to a control
      injection of water. CLINICAL SIGNIFICANCE: Phentolamine Mesylate can be
      considered a safe and effective way of reducing the duration of soft tissue
      anesthesia following a dental appointment. This controlled clinical trial is
      registered at the National Institutes of Health (ClinicalTrials.gov)
      #NCT02861378.

PMID- 29571955
TI  - Eye movement parameters and cognitive functions in Parkinson's disease patients
      without dementia.
AB  - BACKGROUND: Cognitive deficits and eye movement abnormalities have been
      demonstrated to be detectable early clinical manifestations of Parkinson's
      disease. Understanding the relationship between these phenotypes may yield
      insight into the underlying anatomical pathways, assisting in the search for
      simple non-invasive markers of early neurodegeneration. OBJECTIVE: To explore the
      correlations between eye movement parameters with multi-domain cognitive
      functions in patients suffering from Parkinson's disease without dementia.
      METHOD: This is a cross-sectional case-control study of Parkinson's disease
      patients without dementia. Participants underwent global and domain-specific
      cognitive tests and an eye-tracking visual search task to characterize eye
      movement parameters. RESULTS: 62 Chinese Parkinson's disease patients without
      dementia and 62 sex-, age- and education-matched controls were recruited. The
      disease group performed worse in multiple cognitive tasks and exhibited a smaller
      saccadic amplitude. Negative correlations between the eye fixation duration and
      performance in semantic verbal fluency, verbal and visual recognition memory
      tasks were observed, though there was no moderation effect on the correlations
      due to the presence of Parkinson's disease. A common cholinergic deficit in the
      temporal and parietal regions may account for the observed correlations. The lack
      of association with predominantly frontal-executive tasks may suggest specificity
      of these correlations. CONCLUSION: Prolonged visual fixation duration is
      correlated with poorer performance in semantic verbal fluency, verbal and visual
      recognition memory tasks in Parkinson's disease patients without dementia,
      although these correlations are not specific. The clinical utility of eye
      movement parameters as an early marker for cognitive decline in Parkinson's
      disease warrants further exploration in longitudinal studies.

PMID- 29571954
TI  - Antimicrobial efficacy of an apical negative pressure root canal irrigation
      system against intracanal microorganisms.
AB  - OBJECTIVES: The effect of irrigation time on the antimicrobial efficacy of an
      apical negative pressure irrigation system was examined in vitro, followed by
      validation of the antimicrobial effect in vivo using the identified optimal
      irrigation time. METHODS: For the in vitro experiment, 44 extracted premolars
      were decoronated, instrumented, autoclaved and inoculated with Enterococcus
      faecalis (ATCC 29212) for 21 days. Four teeth were used as positive control,
      without irrigation. Each of the remaining 40 teeth was irrigated with 2.5% NaOCl,
      delivered via the EndoVac MacroCannula for 10 s, and subsequently via the EndoVac
      MicroCannula for 15, 30, 45, 60 or 90 s per canal, respectively (N = 8). After
      irrigation, microbial samples were collected, transferred to BHI broth and
      incubated for counting of bacterial colony forming units (CFUs). Based on the in
      vitro results, 8.25% NaOCl was delivered via the EndoVac MicroCannula for 60 s,
      during root canal treatment of 20 human subjects presented with apical
      periodontitis. Microbial samples retrieved in vivo prior to canal instrumentation
      (S0), after chemomechanical debridement (S1) and after irrigation with EndoVac
      (S2) were cultured in an anaerobic chamber for 7 days for CFU evaluation.
      RESULTS: Compared with the control, irrigation significantly reduced bacterial
      populations (p < .05). Irrigation delivery via the EndoVac demonstrated improved
      antibacterial efficacy with increased irrigation time (p < .05). Samples
      retrieved from canals after NaOCl delivery in vivo with the EndoVac for 60 s were
      all culture-negative. CONCLUSIONS: Microbial elimination may be achieved with
      8.25% NaOCl delivered via the EndoVac apical negative pressure irrigation device
      for 60 s. CLINICAL SIGNIFICANCE: With the use of the EndoVac apical negative
      pressure irrigant delivery system, optimal elimination of the intracanal
      bacterial load can only be achieved when sodium hypochlorite is delivered via the
      MicroCannula for at least 60 s per canal.

PMID- 29571956
TI  - The succession of the plant community on a decontaminated radioactive meadow
      site.
AB  - Long-term observation of the succession in a plant community is considered a
      fundamental unit used to investigate the expected consequences of soil
      contamination by radionuclides and to understand restoration of technogeneously
      disturbed ecosystems. The development of arboreal willow meadow under remediation
      of a radioactively contaminated site has been studied for half a century.
      Succession stages in the formation of the de novo community were noted. Changes
      in the floristic composition, soil structure as well as radionuclide activity
      concentrations in topsoil were registered on each step. Technical recultivation
      of the area including covering radioactive wastes with a mixture of sand and
      gravel led to lower the radiation levels and was suitable for decontamination
      during first 5-8 years. This allowed the community to develop with maximal
      effectiveness on the initial steps. Than the covering layer lost its barrier
      functions but no adverse effects at dose rates up to 150 MUGy/h on completion of
      the community formation were registered. Radioecological conditions and changes
      in the plant community development were registered simultaneously on the area
      studied that makes possible to follow main doseforming radionuclides migration
      and to determine main steps of the succession. The study results is a practical
      demonstration that edaphic niches, climatic conditions and soenotic relationships
      between plants play a more important role in the evolution of the studied
      community than the contamination type and radiation exposure levels.

PMID- 29571957
TI  - Commentary on Peltola et al. (2018): "Oxytocin promotes face-sensitive neural
      responses to infant and adult faces in mothers".

PMID- 29571958
TI  - Transplantation of dedifferentiated fat cell-derived micromass pellets
      contributed to cartilage repair in the rat osteochondral defect model.
AB  - BACKGROUND: Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses
      the ability to proliferate effectively and the potential to differentiate into
      multiple linages of mesenchymal tissue; similar to adipose-derived stem cells
      (ASCs). The purpose of this study is to examine the effects of DFAT cell
      transplantation on cartilage repair in a rat model of osteochondral defects.
      METHODS: Full-thickness osteochondral defects were created in the knees of
      Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared
      from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently
      transplanted into the affected right knee of these rats. Defects in the left knee
      were used as a control. Macroscopic and microscopic changes of treated and
      control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To
      observe the transplanted cells, sectioned femurs were immunostained for GFP and
      type II collagen. RESULTS: DFAT cells formed micromass pellets expressing
      characteristics of immature cartilage in vitro. In the DFAT cell-transplanted
      limbs, the defects were completely filled with white micromass pellets as early
      as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the
      defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS
      scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted
      limbs compared to those of the control limbs. The modified O'Driscol histological
      scores for the DFAT cell-transplanted limbs were significantly higher than those
      of the control limbs at corresponding time points. GFP-positive DAFT cells were
      detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post
      operation. CONCLUSIONS: Transplantation of DFAT cell-derived micromass pellets
      contribute to cartilage repair in a rat osteochondral defect model. DFAT cell
      transplantation may be a viable therapeutic strategy for the repair of
      osteochondral injuries.

PMID- 29571959
TI  - Adaptation reveals unbalanced interaction between numerosity and time.
AB  - Processing quantities such as the number of objects in a set, size, spatial
      arrangement and time is an essential means of structuring the external world and
      preparing for action. The theory of magnitude suggests that number and time,
      among other continuous magnitudes, are linked by a common cortical metric, and
      their specialization develops from a single magnitude system. In order to
      investigate potentially shared neural mechanisms underlying numerosity and time
      processing, we used visual adaptation, a method which can reveal the existence of
      a dedicated processing system. We reasoned that cross-adaptation between
      numerosity and duration would concur with the existence of a common processing
      mechanism, whereas the absence of cross-adaptation would provide evidence against
      it. We conducted four experiments using a rapid adaptation protocol where
      participants adapted to either visual numerosity or visual duration and
      subsequently performed a numerosity or duration discrimination task. We found
      that adapting to a low numerosity altered the estimation of the reference
      numerosity by an average of 5 dots, compared to adapting to a high numerosity.
      Similarly, adapting to a short duration altered the estimation of the reference
      duration by an average of 43 msec, compared to adapting to a long duration. In
      the cross-dimensional adaptation conditions, duration adaptation altered
      numerosity estimation by an average of 1 dot, whereas there was not sufficient
      evidence to either support or reject the effect of numerosity adaptation on
      duration judgments. These results highlight that there are partially overlapping
      neural mechanisms which are dedicated for processing both numerosity and time.

PMID- 29571960
TI  - Pathological collecting behavior.

PMID- 29571961
TI  - Investigating the role of personal and context-related factors in convenience
      foods consumption.
AB  - In the scenario of food consumptions, we witness the consumer's growing
      consideration for the "convenience" attribute. Our study intends to understand
      the consumer behaviour towards convenience-processed foods by analysing in a
      single model the role of beliefs, personal traits, social influence and market
      availability. We applied a Structural Equation Model (SEM) to a representative
      sample of 426 Italian consumers. The results show a correlation between intention
      to consume convenience-processed foods and social influence, market availability
      and several personal traits, suggesting strategies for the development of the
      convenience food market.

PMID- 29571962
TI  - Therapeutic plasma exchange: A prospective randomized trial to evaluate 2
      strategies in patients with liver failure.
AB  - OBJECTIVE: To compare two means of performing therapeutic plasma exchange (TPE)
      in patients with liver failure. METHOD: This open-label monocentric randomized
      trial, conducted in a single prestigious general healthcare facility, recruited
      liver failure patients with an indication to receive artificial liver support
      therapy for TPE. All patients underwent TPE procedures and were administered in a
      random sequence: heparin-free or systemic heparinization with unfractionated
      heparin. The primary endpoint was completion of TPE sessions, and the secondary
      endpoints included the safety and efficacy. RESULTS: In the period of the
      studying, there were 164 patients being recruited in and underwent total of 398
      randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In
      unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to
      uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal
      bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2
      of them (0.87%) were switched from heparin-free to unfractionated heparin
      eventually. No significant differences were found between the two groups for
      either RRs or IRs (P > 0.05). CONCLUSION: Heparin-free regimen is feasible and
      safer than systemic heparinization with unfractionated heparin in the process of
      TPEs in patients with liver failure.

PMID- 29571963
TI  - First evidence of DAAM1 localization in mouse seminal vesicles and its possible
      involvement during regulated exocytosis.
AB  - Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a protein
      belonging to the formin family, which regulates, together with the small GTPase
      RhoA, the nucleation and the assembly of actin fibres through Wnt-Dishevelled PCP
      pathway. Its role has been investigated in essential biological processes, such
      as cell polarity, movement and adhesion during morphogenesis and organogenesis.
      In this work, we studied the expression of DAAM1 mRNA and protein by PCR and
      Western blot analyses and its co-localization with actin in adult mouse seminal
      vesicles by immunofluorescence. We show that both proteins are cytoplasmic: actin
      is evident at cell-cell junctions and at cell cortex; DAAM1 had a more diffused
      localization, but is also prominent at the apical plasmatic membrane of
      epithelial cells. These findings support our hypothesis of a role of DAAM1 in
      cytoskeletal rearrangement that occurs during the exocytosis of secretory
      vesicles, and in particular concerning actin filaments. We were also able to
      detect DAAM1 and actin association in the smooth muscle cells that surround the
      epithelium too. In this case, we could only speculate the possible involvement of
      this formin in muscular cells in the maintenance and the regulation of the
      contractile structures. The present results strongly suggest that DAAM1 could
      have a pivotal role in vesicle exocytosis and in the physiology of mouse seminal
      vesicles.

PMID- 29571964
TI  - MicroRNA-21 and the Vulnerability of Atherosclerotic Plaques.

PMID- 29571965
TI  - Targeting Biological Barriers: Turning a Wall into a Therapeutic Springboard.

PMID- 29571966
TI  - Effects of the antipsychotics haloperidol, clozapine, and aripiprazole on the
      dendritic spine.
AB  - Three types of antipsychotics, typical (e.g. haloperidol), atypical (e.g.
      clozapine), and dopamine partial agonist (e.g. aripiprazole), are administered
      for treatment of schizophrenia. These antipsychotics have different efficacy and
      side-effect profiles. We investigated whether aripiprazole, clozapine, and
      haloperidol differentially regulate the dendritic spine through the AKT-GSK-3
      beta cascade. Dissociated cortical neurons from Sprague-Dawley rats were prepared
      and cultured for 28 days. Aripiprazole, clozapine, or haloperidol was
      administered to the rat cortical neurons. The levels of PSD95 protein and AKT-GSK
      3 beta cascade-related proteins were investigated by Western blot. The number of
      spines and PSD95 puncta were investigated by immunofluorescence cell staining.
      Aripiprazole (1 uM or 10 uM) and clozapine (1 uM) increased the levels of PSD95
      protein, the number of spines, phosphorylated Akt Thr308 and Ser473, and
      phosphorylated GSK-3 beta Ser9. On the other hand, haloperidol (1 uM or 10 uM) or
      an inappropriate concentration of clozapine (10 uM) decreased them. A GSK
      inhibitor also increased the levels of PSD-95 protein and caused the same
      morphology. Aripiprazole, clozapine, and haloperidol differentially regulate the
      dendritic spine, and this effect may occur through the AKT-GSK-3 beta cascade.
      Selection and appropriate dose of these antipsychotics may be important for the
      protection of dendritic spines in patients with schizophrenia.

PMID- 29571967
TI  - Functional mechanism of ASP5736, a selective serotonin 5-HT5A receptor antagonist
      with potential utility for the treatment of cognitive dysfunction in
      schizophrenia.
AB  - The 5-HT5A receptor is arguably the least understood 5-HT receptor. Despite
      widespread expression in human and rodent brains it lacks specific ligands. Our
      previous results suggest that 5-HT5A receptor antagonists may be effective
      against cognitive impairment in schizophrenia. In this study, using behavioral,
      immunohistochemical, electrophysiological and microdialysis techniques, we
      examined the mechanism by which ASP5736, a novel and selective 5-HT5A receptor
      antagonist, exerts a positive effect in animal models of cognitive impairment. We
      first confirmed the effect of ASP5736 on cognitive deficits in rats treated
      subchronically with phencyclidine hydrochloride (PCP) using an attentional set
      shifting task. Subsequently, we identified 5-HT5A receptors in dopaminergic
      (DAergic) neurons and parvalbumin (PV)-positive interneurons in the ventral
      tegmental area (VTA) and in PV-positive interneurons in the medial prefrontal
      cortex (mPFC). Burst firing of the DAergic cells in the parabrachial pigmental
      nucleus (PBP) in the VTA, which predominantly project to the mPFC, was
      significantly enhanced by treatment with ASP5736. In contrast, ASP5736 exerted no
      significant effect on either the firing rate or burst firing in the DA cells in
      the paranigral nucleus (PN), that project to the nucleus accumbens (N. Acc.).
      ASP5736 increased the release of DA and gamma-aminobutyric acid (GABA) in the
      mPFC of subchronically PCP-treated rats. These results support our hypothesis
      that ASP5736 might block the inhibitory 5-HT5A receptors on DAergic neurons in
      the VTA that project to the mPFC, and interneurons in the mPFC, and thereby
      improve cognitive impairment by preferentially enhancing DAergic and GABAergic
      neurons in the mPFC.

PMID- 29571968
TI  - Ocular treatment of choroidal melanoma in relation to the prevention of
      metastatic death - A personal view.
AB  - About 50% of patients with choroidal melanoma develop metastatic disease, despite
      successful eradication of the primary tumor. Patient care is complicated by the
      fact that we do not know whether ocular treatment ever influences survival and if
      so in whom. Some authorities believe that metastatic spread is never preventable,
      because it has always occurred by the time the ocular tumor is detected. Others
      hold the view that metastatic spread can occur late, at least in some patients,
      in whom timely and successful treatment is life-saving. Some melanomas never seem
      to metastasize, even if they reach an advanced stage. It is likely that many
      patients are undergoing futile enucleation or experiencing severe ocular
      morbidity and visual loss from excessive radiation safety margins in the hope of
      living longer. Some of these patients would do better with tumor resection, often
      rejected because of concerns about iatrogenic tumor dissemination. At the same
      time, many patients with a small melanoma are being left untreated for years
      until growth is documented, possibly missing opportunities for prolonging life.
      Metastatic disease is highly likely when genetic tumor analysis detects monosomy
      3, chromosome 8q gain, a class 2 gene expression profile, and/or BAP1 loss. Do
      these lethal genetic aberrations ever develop while the patient is under
      observation? If so, can these be predicted by genetic analysis? Do lethal
      mutations and metastasis ever occur because ocular treatment has failed to
      eradicate the tumor completely? Answers to these questions would profoundly
      change the management of patients with uveal melanoma.

PMID- 29571969
TI  - Efficacy of anterior versus posterior per-oral endoscopic myotomy for treating
      achalasia: a randomized, prospective study.
AB  - BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has been demonstrated to
      be safe and effective for treating achalasia. Two approaches-anterior myotomy and
      posterior myotomy-are used during POEM. However, little is known about the
      comparison between the 2 different approaches. The objective of the study is to
      compare the safety and short-term efficacy of the 2 approaches for treating
      achalasia. METHODS: From October 2015 to December 2016, 63 consecutive patients
      with achalasia without prior treatment or sigmoid-type esophagus were
      prospectively recruited. They were randomly assigned to an anterior or posterior
      myotomy group. Clinical data about general characteristics, operative parameters,
      pre- and postoperative Eckardt score, esophageal manometry results, 24-hour pH
      test, and adverse events were recorded and compared between the 2 groups.
      RESULTS: The anterior group included 31 patients and the posterior group 32
      patients. All patients underwent POEM successfully, and treatment success
      (defined as an Eckardt score <=3) was achieved in all patients during a mean
      follow-up of 15.5 months. Mean Eckardt score, lower esophageal sphincter
      pressure, and 4-second integrated relaxation pressure were significantly
      decreased (6.2 +/- 1.3, 37.5 +/- 6.7 mm Hg, and 27.3 +/- 4.9 mm Hg vs .70 +/-
      .70, 12.8 +/- 2.8 mm Hg, and 11.1 +/- 2.3 mm Hg, respectively; P < .01). There
      was no significant difference between the 2 groups in terms of general
      characteristics, treatment success, pre- and postoperative esophageal manometry,
      Eckardt score, and adverse events (P > .05). CONCLUSIONS: The short-term
      treatment efficacy, manometry outcomes, and adverse events were comparable
      between the anterior and posterior myotomy groups. Large-scale studies with long
      term follow-up are warranted for a more definitive conclusion. (Clinical trial
      registration number: ChiCTR-ICR-15007211.).

PMID- 29571970
TI  - Unconventional secretion of viral proteins.
AB  - Although largely less numerous and characterized than bacterial secreted
      effectors, several viral virulence factors are secreted by virus infected cells.
      However, their mode of secretion only starts to be studied at the molecular
      level. Several of these viral effectors are secreted using an unconventional
      secretion pathway, i.e. despite the lack of signal sequence. We here review
      recent results illustrating the diversity of these pathways. In the case of HIV-1
      proteins Tat and matrix (p17) proteins, secretion directly takes place at the
      plasma membrane level following binding to PI(4,5)P2. The secretion of HTLV-I Tax
      was found to partly rely on exocytic pathway intermediates. The secretion
      pathways of VP22 of Herpes simplex virus type I and VP40 of the Ebola virus are
      less well characterized but VP40 can be recruited to the plasma membrane by
      PI(4,5)P2 that thus appears as a key partner enabling the unconventional
      secretion of many viral proteins. Several studies indicated that circulating
      retroviral transactivating proteins Tat and Tax are involved in the development
      of AIDS and HTLV-I associated myelopathy/tropical spastic paraparesis,
      respectively.

PMID- 29571971
TI  - The unconventional secretion of IL-1beta: Handling a dangerous weapon to optimize
      inflammatory responses.
AB  - Interleukin 1beta (IL-1beta) is a major mediator of inflammation, with a
      causative role in many diseases. Unlike most other cytokines, however, it lacks a
      secretory signal sequence, raising intriguing mechanistic, functional and
      evolutionary questions. Despite decades of strenuous efforts in many
      laboratories, how IL-1beta is secreted is still a matter of intense debate. Here,
      we summarize the different mechanisms and pathways that have been proposed for IL
      1beta secretion. At least two of them, namely the endolysosomal vesicle-based and
      gasdermin D-dependent pathways (types III and I in the recent Rabouille's
      classification of unconventional protein secretion), can be triggered in
      monocytes, the main source of IL-1beta in humans, according to the type and
      strength of the pro-inflammatory stimuli. As during the escalation of human
      conflicts, monocytes deploy secretory mechanisms of increasing efficiency and
      dangerousness, shifting from the specific and controlled type III pathway to the
      much faster release of type I. Thus, the different mechanisms are activated
      depending on the severity of the conditions, from the self-limiting type III
      pathways in response of low pathogen load or small trauma, to the uncontrolled
      responses that underlie autoinflammatory disorders and sepsis.

PMID- 29571972
TI  - Immunoinformatics approaches to design a novel multi-epitope subunit vaccine
      against HIV infection.
AB  - The end goal of HIV vaccine designing requires novel strategies to elicit a
      strong humoral and cell-mediated immune response. The emergence of drug
      resistance and the requirement of next line treatment necessitate the finding of
      the potential and immunogenic vaccine candidate. This study employed a novel
      immunoinformatics approach to design multi-epitope subunit vaccine against HIV
      infection. Here, we designed the subunit vaccine by the combination of CTL, HTL
      and BCL epitopes along with suitable adjuvant and linkers. Physiochemical
      characterization of subunit vaccine was assessed to ensure its thermostability,
      theoretical PI, and amphipathic behavior. In further assessment, subunit vaccine
      was found to be immunogenic with the capability to generate humoral and cell
      mediated immune response. Further, homology modeling and refinement was performed
      and the refined modeled structure was used for molecular docking with the immune
      receptor (TLR-3) present on lymphocyte cells. Consequently, molecular dynamics
      simulation ensured the molecular interaction between TLR-3 and subunit vaccine
      candidate. Disulfide engineering was performed by placing the cysteine residues
      in the region of high mobility to enhance the vaccine stability. At last, in
      silico cloning was performed to warrant the translational efficiency and
      microbial expression of the designed vaccine.

PMID- 29571973
TI  - Options for design of real-world impact studies of single-dose vaccine schedules.
AB  - Based on existing evidence for efficacy, savings, and advantages in delivery,
      some countries may elect to pilot or roll out single-dose human papillomavirus
      (HPV) vaccination (instead of, or in combination with, two-dose) in advance of a
      WHO policy decision. Accelerated evidence of population-based effectiveness
      (hereafter referred to as overall effectiveness, OE) of one-dose vaccine programs
      could be gained through regular surveys of HPV prevalence in young women before
      and after vaccination introduction. In order to offer the earliest information on
      OE, one-dose HPV vaccination should target one or more birth cohorts as close as
      possible to the age when sexual activity most often starts in a given population.
      A catch-up one-dose vaccination program of girls up to 18 years of age who would
      have been too old to profit from the introduction of a routine HPV vaccination
      program in preadolescents would minimize the interval between vaccination and the
      possibility to monitor vaccination impact in young women. In addition, catch-up
      is especially desirable in low- and middle-income countries with little access to
      screening as "missed" cohorts may face high risk of cervical cancer death. HPV
      prevalence should be firstly monitored in age groups of women who may already be
      sexually active but still reluctant to admit it and to accept vaginal examination
      for the collection of cervical cells. Hence, HPV testing from urine samples, for
      which good concordance with cervical cells has been proven, offers a feasible
      approach to assess periodically vaccine OE in representative samples of 17-20
      year-old women. This type of observational study would greatly benefit from the
      presence of a population census and the creation of a vaccination registry. A
      real-world demonstration of OE of the new schedule would complement the findings
      of ongoing clinical trials and immunogenicity studies on the efficacy of single
      dose HPV vaccination.

PMID- 29571975
TI  - Asleep at the automated wheel-Sleepiness and fatigue during highly automated
      driving.
AB  - Due to the lack of active involvement in the driving situation and due to
      monotonous driving environments drivers with automation may be prone to become
      fatigued faster than manual drivers (e.g. Schomig et al., 2015). However, little
      is known about the progression of fatigue during automated driving and its
      effects on the ability to take back manual control after a take-over request. In
      this driving simulator study with No=o60 drivers we used a three factorial
      2o*o2o*o12 mixed design to analyze the progression (12o*o5omin; within subjects)
      of driver fatigue in drivers with automation compared to manual drivers (between
      subjects). Driver fatigue was induced as either mainly sleep related or mainly
      task related fatigue (between subjects). Additionally, we investigated the
      drivers' reactions to a take-over request in a critical driving scenario to gain
      insights into the ability of fatigued drivers to regain manual control and
      situation awareness after automated driving. Drivers in the automated driving
      condition exhibited facial indicators of fatigue after 15 to 35omin of driving.
      Manual drivers only showed similar indicators of fatigue if they suffered from a
      lack of sleep and then only after a longer period of driving (approx. 40omin).
      Several drivers in the automated condition closed their eyes for extended periods
      of time. In the driving with automation condition mean automation deactivation
      times after a take-over request were slower for a certain percentage (about 30%)
      of the drivers with a lack of sleep (Mo=o3.2; SDo=o2.1os) compared to the
      reaction times after a long drive (Mo=o2.4; SDo=o0.9os). Drivers with automation
      also took longer than manual drivers to first glance at the speed display after a
      take-over request and were more likely to stay behind a braking lead vehicle
      instead of overtaking it. Drivers are unable to stay alert during extended
      periods of automated driving without non-driving related tasks. Fatigued drivers
      could pose a serious hazard in complex take-over situations where situation
      awareness is required to prepare for threats. Driver fatigue monitoring or
      controllable distraction through non-driving tasks could be necessary to ensure
      alertness and availability during highly automated driving.

PMID- 29571974
TI  - An interactive contouring module improves engagement and interest in radiation
      oncology among preclinical medical students: Results of a randomized trial.
AB  - PURPOSE: Studies have shown significant gaps in knowledge of radiation therapy
      among medical students and primary care providers. The goal of this study was to
      evaluate the effect of an interactive contouring module on knowledge and interest
      in radiation oncology among preclinical medical students. METHODS AND MATERIALS:
      Second-year medical students at the University of California, San Diego were
      randomized to participate in an interactive contouring exercise or watch a
      traditional didactic lecture on radiation oncology. Participants completed
      knowledge tests and surveys at baseline, immediately following the exercise, and
      3 months later. Statistical analysis included Wilcoxon signed-rank test for pre-
      and posttest comparisons and Wilcoxon rank sum test for comparison between
      groups. RESULTS: Forty-three medical students participated in the trial (21 in
      the didactic group; 22 in the contouring group). Students completing the
      contouring module demonstrated similar overall knowledge improvement compared
      with the traditional didactic group (+8.6% vs +6.6%, not significant) but
      endorsed greater engagement on a 5-point Likert-type scale (3.10 vs 3.76, P =
      .02). At 3-month follow-up, there was a nonsignificant trend toward improved
      overall knowledge in the contouring group (43% vs 51%, P = .10), with a
      significance difference in a subset of questions on knowledge of the process of
      radiation therapy as well as side effects (51% vs 75%, P = .002). Students in the
      contouring group demonstrated more interest in pursuing a clinical radiation
      oncology rotation (2.52 vs 3.27, P = .01). CONCLUSIONS: Use of an interactive
      contouring module was an effective method to teach preclinical medical students
      about radiation oncology, with no significant difference in knowledge gained
      compared with a traditional didactic lecture; however, higher engagement among
      students completing the contouring module led to improved retention of knowledge
      of radiation side effects and greater interest in radiation oncology. These data
      suggest a potential benefit of integrating an interactive radiation oncology
      module into the preclinical medical school curriculum.

PMID- 29571976
TI  - The effect of vitamin C and/or E supplementations on type 2 diabetic adult males
      under metformin treatment: A single-blinded randomized controlled clinical trial.
AB  - BACKGROUND AND AIM: Recently, there has been an increasing interest in the
      influence of antioxidant vitamins on the efficacy of oral hypoglycemic therapy in
      type 2 diabetic patients (T2DM). This single-blinded randomized controlled
      clinical trial aimed to investigate the effect of vitamin C and/or E
      supplementation on the efficacy of oral hypoglycemic therapy in T2DM Palestinian
      male patients from the Gaza Strip. METHODS: Forty T2DM male patients aged 40-60
      years on metformin treatment were randomly divided into four groups, each group
      received an additional one of the following daily oral supplements for 90 days:
      placebo; vitamin C; vitamin E and vitamin C plus vitamin E. After overnight
      fasting, venous blood specimens were collected from all individuals into K3-EDTA
      tubes and serum tubes for measuring the biochemical and hematological parameters
      of the study at baseline and after 90 days of vitamins supplementation. RESULTS:
      The results revealed that vitamin C and/or E improve fasting blood sugar (FBS),
      HbA1c, lipid profile, insulin, homeostasis model assessment of insulin resistance
      (HOMA-IR), reduced glutathione (GSH); and Quantitative Insulin Sensitivity Check
      Index (QISCI) compared with diabetic patients group that received placebo.
      CONCLUSION: This study provided additional evidence on the beneficial effects of
      supplementing antioxidant vitamins in T2DM which could improve the clinical
      condition and attenuate or prevent diabetic pathogenesis and complications that,
      secondly to poor glycemic control, could attribute to the imbalance between the
      decline in the endogenous antioxidants and increasing production of the reactive
      oxygen species leading to the oxidant-mediated damage present in the diabetic
      context.

PMID- 29571977
TI  - Non-alcoholic fatty liver disease and associated dietary and lifestyle risk
      factors.
AB  - Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic
      liver disease worldwide with a reported prevalence ranging 20-30% depending on
      the studied populations. The high prevalence of NAFLD is probably due to the
      contemporary epidemics of obesity, unhealthy dietary pattern, and sedentary
      lifestyle. NAFLD patients are at increased risk of cardiovascular and liver
      related mortality. The cornerstone of any treatment regimen for patients with
      NAFLD is lifestyle modification focused on weight loss, exercise, and improving
      insulin sensitivity. The purpose of this review is to outline the effect of diet
      and lifestyle factors on developing NAFLD.

PMID- 29571978
TI  - Hypertension and diabetes mellitus as a predictive risk factors for stroke.
AB  - BACKGROUND: Stroke is becoming a major challenge in healthcare systems, and this
      has necessitated the study of the various risk factors. As the number of people
      with hypertension, diabetes mellitus and obesity increases, the problem is
      expected to worsen. This review paper evaluates what can be done to eliminate or
      reduce the risk of stroke. OBJECTIVE: The aim of the research is to evaluate the
      risk factors for stroke. The paper also aims to understand how these risks can be
      handled to avoid incidences of stroke. METHOD: Published clinical trials of
      stroke risk factors studies were recognised by a search of EMBASE and MEDLINE
      databases with keywords hypertension, blood pressure, diabetes mellitus, stroke
      or cardiovascular disease, or prospective study, and meta-analysis. RESULTS: The
      findings of this review are that the prevention of stroke starts with identifying
      risk factors for stroke, most of the patients diagnosed with stroke have various
      risk factors. Consequently, it is a very significant to identify all the risk
      factors for stroke as well as to teach the patient how to dominate them.
      CONCLUSION: after summarising all the studies mentioned in the paper, it can be
      established that hypertension and diabetes mellitus are a stroke risk factors and
      correlated in patients with atherosclerosis.

PMID- 29571979
TI  - Effects of patchouli and cinnamon essential oils on biofilm and hyphae formation
      by Candida species.
AB  - The prevalence and fatality rates with biofilm-associated candidal infections
      have remained a challenge to the medical fraternity despite major advances in the
      field of antifungal therapy. Traditionally, essential oils (EOs) from the
      aromatic plants have been found to be excellent therapeutic agents to treat
      fungal ailments. The present study explores the antivirulent and antibiofilm
      effects of under explored leaf EOs of Indian patchouli EO extracted from
      Pogostemon heyneanus (PH), Indian cassia from Cinnamomum tamala (CT) and camphor
      EO from C. camphora (CC) against Candida species. The EOs were investigated for
      its efficacy to disrupt the young and preformed Candida spp. biofilms and to
      inhibit the yeast to hyphal transition, a hallmark virulent trait of C. albicans.
      The ability of these EOs to inhibit metabolically active cells was assessed
      through XTT assay. Of these three EOs, CT EO showed enhanced biofilm inhibition
      than others and hence it was further selected to study its biomass inhibition
      potential and exopolysaccharide layer disruption ability. The CT EO reduced the
      biomass of the preformed biofilms of all three Candida strains, which was
      supported by confocal microscopy. It also disrupted the exopolysaccharide layer
      of the Candida strains as shown by scanning electron microscopy. The present
      findings validate the effectiveness of EOs against the virulence of Candida spp.
      and emphasize the pharmaceutical potential of several native but yet unexplored
      wild aromatic plants in the prospect of therapeutic application.

PMID- 29571980
TI  - Brought Down by a Mosquito? West Nile Virus Encephalitis.

PMID- 29571981
TI  - Giardipain-1, a protease secreted by Giardia duodenalis trophozoites, causes
      junctional, barrier and apoptotic damage in epithelial cell monolayers.
AB  - The adhesion of Giardia duodenalis trophozoites to intestinal epithelial cells
      allows the onset and maintenance of giardiasis. During these interactions,
      epithelial cells can be committed to apoptosis by enzymes secreted by the
      parasites, including cysteine proteases that are increasingly identified as
      virulence factors in parasitic protozoa. In this work, a monoclonal antibody
      (mAb1G3) raised against G. duodenalis surface components was found to react with
      a 25 kDa protein expressed in the cell surface and flagella of G. duodenalis
      trophozoites. When trophozoites expressing this protein were cultured with IEC-6
      intestinal epithelial cell monolayers, a dynamic release of this protein was
      observed with mAbIG3. Proteomic analysis identified the protein as a mature
      cathepsin B-like (gCatB) enzyme, whose proteolytic activity, detected in
      zymograms, was eliminated by CatB inhibitor E-64. This protein was named
      giardipain-1 due to its functional papain-like features and was purified by
      affinity chromatography using mAbIG3. Upon exposure to the purified, mature and
      secreted forms of giardipain-1, IEC-6 epithelial cell monolayers displayed
      membrane blebbing and phosphatidylserine exposure on the outer cell surface,
      indicating an apoptotic process. In Madin Darby Canine Kidney (MDCK) cell
      monolayers, giardipain-1 leads to the appearance of pore-like regions and of gaps
      along cell-cell junctions, to decreased transepithelial electrical resistance
      (TER), caspase-3 activation and poly-ADP-ribose polymerase (PARP) fragmentation.
      At early times during exposure, giardipain-1 co-localized at cell-cell junctions,
      associated with occludin and induced the delocalization and degradation of tight
      junction proteins occludin and claudin-1. The damage caused to epithelial
      monolayers by giardipain-1 was blocked by pre-incubation with the CatB B
      Inhibitor E-64. Furthermore, silencing the giardipain-1 gene in trophozoites
      lowered the proteolytic activity of giardipain-1 and reduced the damage in IEC-6
      monolayers. The damage observed appears to be specific to giardipain activity
      since almost no damage was observed when IEC-6 monolayers were incubated with
      papain, a non-related cysteine protease. Hence this study suggests that
      giardipain-1 triggers, in epithelial cells, degradation of cell-cell junctional
      components and apoptotic damage, supporting the notion of giardiapain-1 as a
      virulence factor of Giardia.

PMID- 29571982
TI  - Anomalous coronary arteries arising from the opposite aortic sinus: When to
      intervene?

PMID- 29571983
TI  - Coronary artery abnormalities: Current clinical issues.
AB  - INTRODUCTION AND OBJECTIVE: Patients with anomalous coronary arteries arising
      from the opposite sinus of Valsalva (ACAOS), the left coronary artery (LCA)
      arising from the right sinus or the right coronary artery (RCA) from the left
      sinus with an interarterial course, may present from complete absence of symptoms
      to sudden cardiac death. Although there are guidelines on indications for
      surgery, controversy remains. METHODS: A retrospective review was performed of
      all adult patients diagnosed with ACAOS in our hospital between 2007 and 2016.
      Demographic, clinical, perioperative and follow-up data were collected from
      clinical records and summarized. A review of the published literature was
      performed with special emphasis on clinical presentation, surgical indications
      and results. RESULTS: Seven symptomatic patients underwent surgery (mean age
      57.1+/-8.9 years, two male, five female); they recovered without complications
      and to date have had no recurrence of myocardial ischemia. One asymptomatic
      patient with an anomalous RCA has been medically followed without evidence of
      myocardial ischemia. A 75-year-old woman, diagnosed in 2008 with an anomalous
      LCA, was not referred for surgery and died suddenly six months after diagnosis.
      CONCLUSIONS: Surgery for coronary abnormalities is performed with low risk and
      all published series report full operative survival. The indications for surgery
      are well established for patients with interarterial anomalous LCA and
      symptomatic patients with interarterial anomalous RCA. However, there is some
      uncertainty concerning asymptomatic patients, particularly those with an
      anomalous interarterial RCA, for whom we propose a more assertive approach, if
      young or engaged in strenuous activities.

PMID- 29571984
TI  - A Case of Mast Cell Leukemia: A Review of the Pathophysiology of Systemic
      Mastocytosis and Associated Psychiatric Symptoms.

PMID- 29571985
TI  - Serotonin Syndrome Following Septal Myectomy in Association With Fentanyl and
      Methylene Blue: A Case Report.

PMID- 29571986
TI  - Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell
      lung cancer but retains sensitivity to afatinib.
AB  - OBJECTIVES: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) are promising targeted therapies for EGFR-mutated non-small-cell lung
      cancer (NSCLC) patients. However, acquired resistance inevitably develops.
      Comprehensive and dynamic companion genomic diagnosis can gain insights into
      underlying resistance mechanisms, thereby help oncologists and patients to make
      informed decision on the potential benefit of the treatment. MATERIALS AND
      METHODS: A 67-year-old male who was initially diagnosed of EGFR L858R-mediated
      NSCLC received multiple lines of chemotherapy and EGFR TKI therapies after
      surgery. The EGFR mutational status of individual metastatic lesion was
      determined by genetic testing of the tumor tissue biopsies using next generation
      sequencing (NGS) throughout the patient's clinical course. An acquired
      potentially drug-resistant EGFR mutation was functionally validated in vitro and
      its sensitivity to different EGFR TKIs was assessed simultaneously. RESULTS: We
      have identified distinct resistance mechanisms to EGFR blockade in different
      metastatic lung lesions. Acquired EGFR T790M was first detected that leads to the
      resistance to the gefitinib treatment. Consequently, osimertinib was
      administrated and the response lasted until disease progressed. We identified a
      newly acquired EGFR L718V mutation in one lesion in conjunction with L858R, but
      not T790M, which showed stable disease on the following erlotinib treatment,
      while EGFR C797S together with L858R/T790M was detected in the other lesion that
      continuously progressed. In vitro functional studies demonstrated that EGFR
      L858R/L718V confers resistance to osimertinib, but retains sensitivity to the
      second generation TKI afatinib. CONCLUSION: We reported that distinct resistance
      mechanisms could arise in different metastases within the same patient in
      response to EGFR blockade. We also demonstrated in vitro that EGFR L718V mutation
      mediates resistance to osimertinib, but retains sensitivity to afatinib. We
      evidenced that dynamic companion genomic diagnosis offers valuable information to
      help define the mechanisms of drug resistance and to guide the selection of
      subsequent treatment.

PMID- 29571987
TI  - Clinical analysis by next-generation sequencing for NSCLC patients with MET
      amplification resistant to osimertinib.
AB  - INTRODUCTION: The efficacy of osimertinib was compromised by the development of
      resistance mechanisms, such as MET amplification. However, cohort studies of
      osimertinib resistance mechanism, and the correlation of MET and progression-free
      survival (PFS) after osimertinib resistance have been poorly investigated.
      OBJECTIVES: This study was carried out to study the acquired MET amplification
      after osimertinib resistance in advanced lung adenocarcinoma patients, and
      interrogate the correlation of clinical prognosis and MET amplification. METHODS:
      We performed capture-based sequencing on longitudinal plasma and tissue samples
      obtained before osimertinib treatment and after resistance development from lung
      adenocarcinoma patients to investigate the underlying resistance mechanism. We
      also investigated the correlation of MET amplification and patient prognosis
      after osimertinib resistance using Kaplan-Meier analysis. RESULTS: Paired
      biopsies before osimertinib treatment and after the resistance development
      revealed underlying resistance mechanisms. In addition, a cohort of 13 patients
      who developed disease progression after osimertinib resistance was investigated.
      Patients with MET amplification after osimertinib resistance commonly had
      inferior median progression-free survival (mPFS) than patients without MET
      amplification appearance or increase (3.5 months vs. 9.9 months, p = .117).
      Patients in MET amplification group also displayed poor median overall survival
      (mOS) compared to MET amplification negative group (15.6 months vs. 30.7 months,
      p = .885). Furthermore, combinatorial treatment of first/third-generation EGFR
      TKI and crizotinib was efficaciously administrated into two patients with newly
      acquired MET amplification after osimertinib resistance. Partial responses were
      achieved by them, both clinically and radiographically. CONCLUSIONS: We
      investigated the osimertinib resistance mechanism in a small cohort of lung
      adenocarcinoma patients, and demonstrated MET amplification was correlated with
      inferior PFS/OS after osimertinib treatment. Moreover, we reported the first
      clinical evidence of efficacy generated by combination of first-generation EGFR
      TKI icotinib and crizotinib after the resistance to osimertinib.

PMID- 29571988
TI  - MiR-192 and miR-662 enhance chemoresistance and invasiveness of squamous cell
      lung carcinoma.
AB  - OBJECTIVES: Overexpression of miR-192, miR-192* and miR-662 was previously found
      to correlate with poor prognosis of early-stage squamous cell lung cancer (SCC)
      patients. In this study, we investigated the relevance of these miRNAs to cancer
      cell biology and chemoresistance. MATERIALS AND METHODS: MiRNA expression profile
      was analysed in 10 non-small cell lung cancer (NSCLC) cell lines using RT-qPCR.
      H520 and H1703 cells were transfected with miRNA inhibitors (anti-miR-192, -192*
      and -662) for functional studies. Chemoresistance to cisplatin and etoposide was
      evaluated using MTT colorimetric assay. H520 cells were subjected to 3D soft-agar
      colony formation assay and H1703 cells to wound healing assay. Whole
      transcriptome analysis was used to assess the effect of miR-192 and miR-662
      inhibition on gene expression. RESULTS: SCC cell lines, H520 and H1703, differed
      in miRNA expression and phenotypic features. MiR-192 and miR-662 inhibition
      decreased clonogenicity and motility of SCC cells. MiR-192 and miR-662 inhibition
      sensitized SCC cells to etoposide but not to cisplatin. Whole transcriptome
      analysis revealed genes regulated by miR-192 and miR-662 in SCC, relevant to
      maintaining chemoresistance, invasiveness, epithelial-mesenchymal transition
      (EMT) and immune evasion. CONCLUSIONS: We showed for the first time that miR-192
      and miR-662 have functional role in SCC cells. Our findings suggest that
      targeting these miRNAs may impact both chemoresistance and invasiveness of SCC,
      and add to the evidence linking these aspects of tumour biology. Overexpression
      of miR-192 and miR-662 might be useful as a marker of resistance to etoposide.

PMID- 29571989
TI  - Neoadjuvant treatment followed by surgery versus definitive chemoradiation in
      stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the
      oncologic group for the study of lung cancer (Spanish Radiation Oncology
      Society).
AB  - OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer
      (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in
      this patient population, we conducted a multi-institutional retrospective study
      comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to
      definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247
      patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either
      CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were
      identified. A centralized review was performed to ensure resectability. A
      propensity score matched analysis was carried out to balance patient and tumor
      characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were
      treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%)
      received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery
      consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients;
      17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log
      rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p <
      0.001) were significantly higher in the CRTS group. This survival advantage for
      CRTS was maintained in the subset comparison between the lobectomy subgroup
      versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001),
      but not in the comparison between the pneumonectomy subgroup and dCRT.
      CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or
      chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and
      PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2
      NSCLC.

PMID- 29571990
TI  - Response to crizotinib in advanced ALK-rearranged non-small cell lung cancers
      with different ALK-fusion variants.
AB  - INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements are present in
      approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK
      rearrangement can be effectively treated with crizotinib. However, magnitude and
      duration of responses are found to be heterogeneous. This study explored the
      clinical efficacy of crizotinib in different ALK variants. METHODS: Among 96 ALK
      rearrangement patients treated with crizotinib, 60 patients were identified with
      tumor specimens that could be evaluated by next-generation sequencing (NGS). We
      retrospectively evaluated the efficacy of crizotinib in different ALK variants.
      RESULTS: The median Progression-free survival (PFS) of the 96 ALK-rearrangement
      patients was 14.17 months. Among the 60 patients with NGS results, the most
      frequent variants were variant 3a/b (33.33%), variant 1 (23.33%) and variant 2
      (15.00%). The percentage of rare EML4-ALK variants and non EML4-ALK variants were
      10.00% and 18.33%. Survival analysis showed that patients with variant 2 appeared
      to have longer PFS than others (P = .021); also, patients with TP53 mutation
      seemed to have an unfavorable PFS than those with TP53 wild-type with a
      borderline p value (P = .068). After adjusting for other baseline
      characteristics, EML4-ALK variant 2 was identified as an important factor for a
      better PFS of crizotinib. We also found that patients with variant 3a/b had
      shorter duration of response to crizotinib; however, no significant difference of
      PFS was observed between the PFS of variant3a/b and non-v3 EML4-ALK variants.
      CONCLUSIONS: Our results indicate prolonged PFS in patients with EML4-ALK variant
      2.

PMID- 29571991
TI  - High expression of P-cadherin is significantly associated with poor prognosis in
      patients with non-small-cell lung cancer.
AB  - OBJECTIVES: Placental (P)-cadherin expression is associated with malignant
      phenotype of cancer cell. The loss of E-cadherin has been thought to play a key
      role in tumor progression in several cancers. In this study, we aimed to clarify
      the role of P-cadherin expression in non-small-cell lung cancer (NSCLC).
      MATERIALS AND METHODS: NSCLC patients (n = 172) were enrolled in this study;
      among them, 107 harbored adenocarcinomas, and 65 had squamous cell carcinomas. We
      examined P-cadherin and E-cadherin expression by immunohistochemical analysis and
      assessed the associations between each cadherin expression and both cadherin
      expression patterns with clinicopathological factors and prognosis. To
      investigate the pathway to acquire tumor progression associated with P-cadherin
      and E-cadherin, we examined p120 catenin localization by immunohistochemical
      analysis. RESULTS: High P-cadherin expression was significantly associated with
      lymphatic metastasis, pathological stage, and Ki-67 proliferation index (P < .05,
      respectively). Low E-cadherin expression was significantly associated with
      maximum standardized uptake value, lymphatic metastasis, and pathological stage
      (P < .05, respectively). The cytoplasmic p120 catenin localization was associated
      with the low E-cadherin and high P-cadherin expression group (P < .001). High P
      cadherin expression was associated with shorter disease-free survival (P = .044)
      and shorter overall survival (OS; P = .044). The low E-cadherin and high P
      cadherin expression group was associated with shorter OS (P = .024). CONCLUSIONS:
      High P-cadherin expression was associated with tumor progression and poor patient
      survival in NSCLC. In these patients, the low E-cadherin expression might be
      associated with tumor progression involving cytoplasmic p120 catenin.

PMID- 29571992
TI  - The eighth TNM classification system for lung cancer: A consideration based on
      the degree of pleural invasion and involved neighboring structures.
AB  - OBJECTIVES: The eighth tumor-node-metastasis (TNM) classification system for lung
      cancer has been used since January 2017 and must be applied to an individual
      institution's database. METHODS: We analyzed pathological stage data of 2756
      patients who underwent resection of non-small-cell lung cancer, particularly in
      terms of the degree of visceral pleural invasion and involved neighboring
      structures. RESULTS: Few patients had stage IIA disease (103, 4%); stratification
      between stages IB and IIA was insufficient (p = 0.129). When T2a tumors were
      divided into PL1 and PL2 subgroups based on the degree of pleural invasion, there
      was a significant prognostic difference between the subgroups (p < 0.001). By
      incorporating T2a tumors with PL2 (T2a-PL2) into the T2b category, modified
      stages IB, IIA (234, 8%), and IIB were well stratified (IB vs. IIA, p < 0.001;
      IIA vs. IIB, p = 0.011). Focusing on T3 tumors with PL3 (T3-PL3) invading
      neighboring structures, multivariate analysis for surveying pT3N0-2M0 tumors
      revealed that completeness of resection (p = 0.002), implementation of any
      postoperative therapies (p = 0.003), and subcategorization of whether only the
      pleura was infiltrated or other deeper structures were also invaded (p = 0.024)
      were significant and crucial predictors. N2 disease showed worse outcome than N0
      1 diseases, with marginal difference (p = 0.054). CONCLUSION: T2a-PL2 tumors
      could be categorized into a worse prognostic T2b category. For T3-PL3 tumors
      involving resectable neighboring organs, subcategorization of whether there is
      only pleura infiltration (T3a) or other deeper structure invasion (T3b) could be
      a practical consideration.

PMID- 29571993
TI  - Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential
      benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?
AB  - The current standard of care for the management of inoperable stage 3 non-small
      cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using
      radiotherapy dose-fractionation and chemotherapy regimens that were established 3
      decades ago. In an attempt to improve the chances of long-term control from cCRT,
      dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised
      control study comparing the standard 60 Gy in 30 fractions with a high-dose arm
      receiving 74 Gy in 37 fractions. Following the publication of this trial the
      thoracic oncology community were surprised to learn that there was worse survival
      in the dose-escalated arm and that for now the standard of care must remain with
      the lower dose. In this article we review the RTOG 0617 paper with subsequent
      analyses and studies to explore why the use of dose-escalated cCRT in stage 3
      NSCLC has not shown the benefits that were expected. The overarching theme of
      this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of
      patient, tumour, and clinical factors may obscure the potential benefits of dose
      escalation by causing imbalances in the arms of studies such as RTOG 0617. We
      also examine recent advances in the staging, management, and technological
      delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT
      trials in the future and ensure that any potential benefits of dose-escalation
      can be detected.

PMID- 29571994
TI  - Eribulin inhibits the growth of small cell lung cancer cell lines alone and with
      radiotherapy.
AB  - OBJECTIVES: Small cell lung cancer (SCLC) patients of all stages are treated with
      etoposide and cisplatin or carboplatin with or without surgery or chest
      radiotherapy. Initial response rates are >=70% however the majority of patients
      relapse and are resistant to additional therapies due to pan-resistance to these
      salvage therapies. Therefore, new treatments are urgently needed. The non-taxane
      microtubule inhibitor eribulin has produced responses in heavily pretreated
      breast cancer patients. We evaluated the efficacy of eribulin alone and in
      combination with radiation in a panel of SCLC cell lines established from
      patients prior to or after receiving chemotherapy and or radiation. MATERIAL AND
      METHODS: Growth inhibition by eribulin alone, radiation alone and the combination
      was assessed by MTS assay and clonogenic survival. Eribulin induced cell cycle
      arrest was evaluated by FACS. Apoptosis was evaluated by using the Caspase-GLO
      3/7 luminescent plate assay and by the Vybrant apoptosis assay with analysis by
      FACS. RESULTS: Eribulin mesylate inhibited the growth of all 17-SCLC lines at
      concentrations of <=10 nM which is a clinically achievable dose. Growth
      inhibition was not significantly different between cell lines established prior
      to or after chemotherapy (p = .5). Concurrent eribulin + radiation induced a
      greater G2-M arrest, an increase in apoptotic cells and increased growth
      inhibition over radiation alone. CONCLUSIONS: Eribulin was highly active alone
      and in combination with radiation in treatment naive SCLC lines and lines
      established from previously treated patients. In vivo pre-clinical studies of
      eribulin alone and in combination with radiation should be considered in SCLC
      cell lines.

PMID- 29571995
TI  - Pre-operative quantification of pulmonary function using hybrid-SPECT/low-dose
      CT: A pilot study.
AB  - RATIONALE: Pre-operative lobar function is estimated by scintigraphy in patients
      with pulmonary malignancies and compromised function. This study compared the
      lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT
      (SPECT/ldCT) analyzed manually and semi-automatic. METHODS: Retrospective
      analysis on 39 patients (m/f = 25/14; age: 72.5 [22-89] years) with indication
      for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT.
      Data was analyzed manually and by semi-automatic software. Readers' confidence in
      3D-segmentation was scored by two independent readers. Interrater agreement was
      calculated. In addition, Spearman's rank correlation and Wilcoxon's test were
      used. RESULTS: Results from PS differed significantly from SPECT/ldCT processed
      manually or semi-automatically in 4/5 lobes (total difference <=21.6%; rho
      >=0.44) and in 3/5 (total difference 21.6%; rho >=0.37), respectively. Readers'
      confidence in 3D-segmentation showed a perfect interrater agreement (kappa =
      0.98). CONCLUSION: Quantification of lobar perfusion by SPECT/ldCT differs
      significantly from planar scintigraphy (e.g., with potential influence on
      therapy). The semi-automatic software analysis provides an applicable
      methodology.

PMID- 29571996
TI  - Optimal surgical approach to thymic malignancies: New trends challenging old
      dogmas.
AB  - Until recently, the surgical approach to thymic tumors has remained basically
      unchanged. The collaborative effort led by ITMIG with the collaboration of
      regional and society-based interest groups (ESTS, JART) produced an enthusiastic
      surge of interest in testing the new technological advances in thoracic surgery
      and many historical dogmas in thymic surgery have been questioned and challenged.
      The present review addresses the new trends in the optimal surgical management of
      thymic tumors based on the review of the current literature. 1. Minimally
      invasive techniques (MIT) including video-assisted thoracic surgery (VATS) and
      robotic-assisted thoracic Surgery (RATS) are now to be considered the standard of
      care in early-stage thymic tumors. MIT are no inferior to open approaches in
      terms of postoperative complications, loco-regional recurrence rates and
      survival. MIT are associated with a shorter length of stay, reduced
      intraoperative blood loss and better cosmetic results. 2. The adoption of the
      ITMIG/IASLC TNM staging system for thymic tumors requires a paradigm shift among
      thoracic surgeons to include regional lymphadenectomy according to the
      IASLC/ITMIG nodal map in the surgical management of thymic tumors. 3. A limited
      thymectomy instead of total thymectomy along with the removal of the thymic tumor
      in nonmyasthenic Stage I-II tumors has been proposed by some authors, although
      the results are not uniform. Until more mature data is available, adherence to
      the current guidelines recommending total thymectomy in addition to thymomectomy
      is always indicated. 4. In locally-advanced Stage IVa patients with pleural
      involvement, major pleural resections, including pleurectomy/decortication or
      extrapleural pneumonectomy are indicated, provided a complete resection of the
      pleural deposits is anticipated, usually in a multidisciplinary setting, with
      excellent long-term results. The incorporation of these new concepts and
      techniques in the surgical armamentarium of the thoracic surgeons dealing with
      thymic malignancies will certainly be of help in the optimal management of these
      patients.

PMID- 29571997
TI  - Histology significantly affects recurrence and survival following SBRT for early
      stage non-small cell lung cancer.
AB  - BACKGROUND: Contrary to prevailing notions of uniform efficacy regarding
      stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung
      cancer (NSCLC), a recent report has indicated increased risk of local failure for
      squamous cell carcinoma (SCC). As those data have not been corroborated by other
      studies, we performed a multi-institutional analysis to evaluate the influence of
      histology on post-SBRT outcomes. MATERIALS AND METHODS: Records from 152
      consecutive patients who received SBRT for primary early-stage NSCLC at two
      academic medical centers were retrospectively assessed. Primary comparison was
      between SCC and adenocarcinoma. Patient outcomes including actuarial recurrences
      and overall survival were calculated using the Kaplan-Meier method. Univariable
      and multivariable logistic regression analyses addressed associated factors.
      RESULTS: At a median follow-up of 44 months, patients with SCC had an increased
      risk of local, (hazard ratio (HR) (95% confidence interval (CI)): 1.69 (1.05
      2.73), p = 0.032), regional (HR (95% CI): 2.03 (1.24-3.33), p = 0.005), and
      distant failure (HR (95% CI): 1.71 (1.06-2.77), p = 0.036). Median times to local
      (32 m vs 50m, p = 0.023), regional (26 m vs 50 m, p = 0.011), and distant (26 m
      vs 50 m, p = 0.024) failure were all significantly reduced in SCC histology. SCC
      histology was also independently associated with an increased risk for death (HR:
      1.80 (1.10-2.94), p = 0.019) and had a 5-yr overall survival of 26%, versus 41%
      for adenocarcinoma (p = 0.016). CONCLUSIONS: This multi-institutional analysis
      corroborates that SCC histology is independently predictive for local, regional,
      and distant recurrence and worse overall survival. Future data are needed to
      determine if treatment paradigms should differ by histology for early stage
      NSCLC.

PMID- 29571998
TI  - Identification of a novel KIF13A-RET fusion in lung adenocarcinoma by next
      generation sequencing.
AB  - OBJECTIVES: RET fusions have been reported in 1-2% of lung adenocarcinomas, and
      represent an actionable target. Patients whose tumors possess RET fusion are
      associated with clinical benefit from the treatment with multi-kinase inhibitors
      such as cabozantinib and vandetanib. Further molecular screening for RET fusions
      is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain
      involving exons 1-18 of KIF13A and exons 12-20 of RET was identified in a lung
      cancer specimen from an 74-year-old Asian never smoker by next-generation
      sequencing (NGS) during clinical care. The patient was negative for EGFR, ALK,
      ROS1 and other putative driver alterations. Fusion analysis is consistent with
      other described RET fusions and is predicted to result in aberrant constitutive
      activation caused by dimerization and sensitivity to RET-directed therapies. We
      describe a novel RET-fusion with molecular characteristics consistent with RET
      driven non-small cell lung cancer. Our case expands the spectrum of RET fusion
      partners and supports broad molecular profiling in non-small cell lung cancer
      optimizing patient therapeutic options. The new RET fusion has immediate clinical
      implications for cancer patients.

PMID- 29571999
TI  - The ratio of cancer cells to stroma within the invasive area is a histologic
      prognostic parameter of lung adenocarcinoma.
AB  - OBJECTIVES: This study evaluated whether the proportion of cancer cells to non
      cancerous stroma within the invasive area is associated with the prognosis of
      patients with lung adenocarcinoma. MATERIALS AND METHODS: A total of 127 patients
      with lung adenocarcinomas with tumors larger than 3 cm in total size were
      enrolled in this study. We classified the tumors according to the ratio of area
      occupied by cancer cells within the invasive area (Type A: more than 50% of the
      invasive area, Type B: 10-50%, and Type C: less than 10%) and analyzed the
      clinicopathological differences between Types A, B, and C. RESULTS: The invasive
      size of Type A tumors (n = 35) was significantly larger than those of the other
      two tumor types; however, there was no significant difference in the invasive
      size between Types B (n = 65) and C (n = 25) tumors. The recurrence-free survival
      time of patients with Type C tumors was significantly longer than those of
      patients with Type A and B (P < .001) tumors. Multivariate analysis revealed that
      Type C tumor was an independent favorable prognostic factor (P = .037) but that
      invasive size was not. The invasive area of Type C tumor was composed of a
      significantly higher proportion of collapsed elastic fibers than the invasive
      areas of Type A and B tumors (P < .001). CONCLUSION: A lower cancer cell to
      stroma ratio within the invasive area could be a significant prognostic factor in
      lung adenocarcinoma, suggesting that not only the invasive size but also the
      invasive character might be an important histologic prognostic parameter.

PMID- 29572000
TI  - PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK
      rearrangements.
AB  - OBJECTIVES: Expression of programmed cell death-ligand 1 (PD-L1) has been
      associated with clinical outcome of programmed cell death-1 (PD-1) pathway
      blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay,
      the only companion diagnostic for pembrolizumab therapy, has revealed that ~30%
      of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1
      expression in NSCLCs with known driver oncogenes has remained unclear, however.
      MATERIALS AND METHODS: We retrospectively evaluated PD-L1 expression with the
      22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with
      EGFR mutations and 9 with ALK rearrangements, all of whom were treated with
      corresponding tyrosine kinase inhibitors (TKIs). RESULTS: Of the 80 tumors
      analyzed, 26 (32.5%) had a PD-L1 tumor proportion score (TPS) of 1%-49% and 9
      (11.3%) had a PD-L1 TPS of >=50%; 35 (43.8%) thus had a PD-L1 TPS of >=1%. Of the
      71 tumors with EGFR mutations, 23 (32.4%) had a PD-L1 TPS of 1%-49% and 7 (9.9%)
      had a PD-L1 TPS of >=50%. A PD-L1 TPS of >=1% was not associated with any
      clinical characteristic examined. Progression-free survival on initial TKI
      treatment was significantly poorer for patients with a PD-L1 TPS of >=1% than for
      those with a PD-L1 TPS of <1% (p = .016). CONCLUSIONS: A subset of patients with
      EGFR mutations or ALK rearrangements had a PD-L1 TPS of >=50%. Prospective
      studies are thus warranted to examine the efficacy of PD-1/PD-L1 inhibitors in
      such patients.

PMID- 29572001
TI  - Prognostic significance of 18F-fluorodeoxyglucose uptake of bone marrow measured
      on positron emission tomography in patients with small cell lung cancer.
AB  - OBJECTIVES: We investigated whether 18F-fluorodeoxyglucse (FDG) uptake of bone
      marrow (BM) on positron emission tomography/computed tomography (PET/CT) has
      implications for predicting clinical outcomes in patients with small cell lung
      cancer (SCLC). METHODS: We retrospectively enrolled 70 SCLC patients who
      underwent FDG PET/CT prior to treatment. On PET/CT, maximum FDG uptake of all
      tumor lesions (Tmax), coefficient of variation (COV) of FDG uptake of primary
      tumor, and mean FDG uptake of BM (BM SUV) were measured. The relationships of BM
      SUV with PET/CT parameters of SCLC and serum markers were evaluated. Univariate
      and multivariate analyses were performed to assess the significance of BM SUV for
      predicting progression-free survival (PFS) and overall survival (OS). RESULTS: BM
      SUV had significant positive correlations with Tmax, COV of primary tumor, white
      blood cell count, and serum C-reactive protein level (p < .05). On univariate
      analysis, BM SUV showed significant association with only PFS (p = .006). On
      multivariate analysis, Veterans Administration Lung Cancer Study Group (VALSG)
      stage, N stage, M stage, Tmax, and BM SUV were independent prognostic factors for
      PFS (p < .05) and, for OS, VALSG stage and M stage were independent prognostic
      factors (p < .05). Among patients with limited disease, patients with high FDG
      uptake of BM had significantly worse PFS than did those with low FDG uptake of BM
      (p < .05), but, there was no significant difference in PFS between patients with
      extensive disease and patients with limited disease and high FDG uptake of BM (p
      > .05). CONCLUSION: FDG uptake of BM was an independent predictor of disease
      progression in SCLC patients. Patients with limited disease and high FDG uptake
      of BM had similar PFS to those with extensive disease.

PMID- 29572003
TI  - Clinicopathological characteristics of POLE mutation in patients with non-small
      cell lung cancer.
AB  - BACKGROUND: Mutations in polymerase epsilon (POLE), a DNA polymerase involved in
      DNA replication and repair, have been investigated in endometrial cancers and
      response to programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1)
      immunotherapy. However, the frequency of POLE gene mutation in patients with non
      small cell lung cancer (NSCLC) has not been reported. MATERIALS AND METHODS: We
      assessed POLE mutation in 319 patients with NSCLC by next-generation sequencing
      (NGS) of 416 cancer-associated genes. Expression of PD-L1, DNA mismatch repair
      proteins (MMR), and the abundance of CD8-positive tumor infiltrating lymphocytes
      (TILs) were assayed by immunohistochemistry. Progression-free survival (PFS) was
      evaluated using the Kaplan-Meier method and compared among groups using log-rank
      tests. RESULTS: Nine of the 319 patients (2.8%) harbored POLE mutation. All nine
      had adenocarcinomas. The median tumor mutational burdens (TMBs) were 12.2/Mb and
      7.8/Mb in patients with and without POLE mutation, respectively (P = 0.026). PD
      L1, MMR (including MSH2, MSH6, MLH1 and PMS2), and CD8-positive TILs were
      evaluated in all nine patients. No microsatellite instability was detected, but
      seven patients had high levels of CD8-positive TILs and five demonstrated PD-L1
      staining >25%. One patient receiving the PD-L1 antibody atezolizumab demonstrated
      a partial response, with a PFS of >8 months. CONCLUSION: POLE mutation represents
      an uncommon phenotype in NSCLC. TMB, PD-L1 expression, and CD8-positive TILs were
      all higher in patients with mutant compared with wild-type POLE. POLE mutation
      may thus represent a candidate biomarker for response to immunotherapy in
      patients with NSCLC.

PMID- 29572002
TI  - Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of
      pleural malignancy.
AB  - INTRODUCTION: Pleural Malignancy (PM) is often occult on subjective radiological
      assessment. We sought to define a novel, semi-objective Magnetic Resonance
      Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density
      (MVD) and applicable to minimal pleural thickening. MATERIALS AND METHODS: 60
      consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then
      pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in
      multiple regions of interest (ROI) at multiple time-points, generating ROI
      SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic
      performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in
      at least one ROI at or before 4.5 min) was compared with subjective MRI and
      Computed Tomography (CT) morphology results. MSIG was correlated against tumour
      MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma. RESULTS:
      71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE
      sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive
      predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE
      performance was similar or superior to subjective CT and MRI. MSIG correlated
      with MVD (r = 0.4258, p = .02). DISCUSSION: ECE is a semi-objective, perfusion
      based biomarker of PM, measurable in minimal pleural thickening. Further studies
      are warranted.

PMID- 29572004
TI  - Phase II trial of preoperative pemetrexed plus carboplatin in patients with stage
      IB-III nonsquamous non-small cell lung cancer (NSCLC).
AB  - OBJECTIVES: The combination of pemetrexed and carboplatin is a standard first
      line treatment for patients with advanced NSCLC. In this pilot phase II trial, we
      evaluated the feasibility of using pemetrexed and carboplatin as neoadjuvant
      therapy, prior to definitive surgical resection, for patients with localized
      NSCLC. PATIENTS AND METHODS: Patients with potentially resectable, previously
      untreated, clinical stage IB-III, nonsquamous NSCLC were eligible for this trial.
      All patients received 4 cycles of pemetrexed (500 mg/m2) and carboplatin (AUC
      6.0) administered at 21 day intervals. Three to 6 weeks after completion of
      chemotherapy, definitive surgical resection was attempted. The primary endpoint
      of this trial was the 3-year survival rate. RESULTS: Forty-six patients began
      protocol treatment, and 40 completed 4 courses of pemetrexed/carboplatin.
      Surgical resection was performed in 27 patients (59%); all had pathologic partial
      responses. The estimated 3-year survival rate for the entire group was 46%.
      Toxicity of neoadjuvant therapy was consistent with toxicity previously reported
      with pemetrexed/carboplatin. CONCLUSIONS: Administration of 4 courses of
      pemetrexed/carboplatin was feasible. The efficacy was similar to neoadjuvant
      regimens previously investigated. A significant number of patients 19 of 46 (41%)
      in this trial did not have surgical resection after neoadjuvant therapy. Further
      investigation of the role of neoadjuvant pemetrexed/carboplatin requires a
      larger, randomized clinical trial.

PMID- 29572005
TI  - Programmed cell death-ligand 1 (PD-L1) expression is associated with RAS/TP53
      mutations in lung adenocarcinoma.
AB  - INTRODUCTION: The systematic assessment of anti-programmed cell death ligand 1
      (PD-L1) expression by immunohistochemistry (IHC) in lung adenocarcinomas is
      becoming standard practice. However, the assessment of PD-L1 expression on small
      tissue specimens needs to be evaluated and the association with other features
      more thoroughly analyzed. METHODS: This retrospective single center study
      evaluated the immunohistochemical expression of the SP263 anti-PD-L1 antibody on
      tissue microarrays (TMA) of 152 surgically resected lung adenocarcinomas, using a
      25% positivity threshold. The positive cases and 50 randomly chosen negative
      cases in tissue microarray (TMA) were reassessed on whole tissue sections. The
      results were correlated to clinical, histopathological and to molecular data
      obtained through the screening of 214 mutations in 26 genes (LungCarta panel,
      Agena Biosciences). RESULTS: Among 152 primary lung adenocarcinomas, 19 cases
      (13%) showed PD-L1 expression. The agreement between TMA and whole tissue
      sections was 89%, specificity was 97%. PD-L1 expression was correlated to RAS
      mutations (p = .04), RAS/TP53 co-mutations (p = .01) and to the solid or acinar
      subtype (p = .048). CONCLUSIONS: With the SP263 PD-L1 antibody, small samples
      appear as a reliable means to evaluate the PD-L1 status in lung adenocarcinoma.
      The association between PD-L1 expression and RAS/TP53 mutations may have clinical
      relevance to predict the efficacy of PD-1/PD-L1 immune checkpoints inhibitors.

PMID- 29572006
TI  - Challenges and future direction of molecular research in air pollution-related
      lung cancers.
AB  - Hazardous air pollutants or chemical release into the environment by a variety of
      natural and/or anthropogenic activities may give adverse effects to human health.
      Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon
      monoxide (CO), heavy metals and particulate matter (PM) affect number of
      different human organs, especially the respiratory system. The International
      Agency for Research on Cancer (IARC) reported that ambient air pollution is a
      cause of lung cancer. Recently, the agency has classified outdoor air pollution
      as well as PM air pollution as Group 1 carcinogens. In addition, several
      epidemiological studies have shown a positive association between air pollutants
      to lung cancer risks and mortality. However, there are only a few studies
      examining the molecular effects of air pollution exposure specifically in lung
      cancer due to multiple challenges to mimic air pollution exposure in basic
      experimentation. Another major issue is the lack of adequate adjustments for
      exposure misclassification as air pollution may differ temporo-spatially and
      socioeconomically. Thus, the purpose of this paper is to review the current
      molecular understanding of air pollution-related lung cancer and potential future
      direction in this challenging yet important research field.

PMID- 29572007
TI  - PD-L1 expression in large cell neuroendocrine carcinoma of the lung.
AB  - OBJECTIVES: Large cell neuroendocrine carcinoma of the lung (LCNEC) is associated
      with an unfavorable prognosis and only few patients are eligible for surgery. In
      most patients, chemotherapy is recommended alone or in addition to resection.
      Novel immunotherapies blocking the PD-L1 pathway have been introduced into
      therapeutic regimens for NSCLC with great success. In order to evaluate a
      possible efficacy of an anti-PD-L1 therapy, we analyzed the frequency of PD-L1
      expression in LCNEC. MATERIAL AND METHODS: We retrospectively reviewed data from
      76 patients with LCNEC treated in our institution between 1998 and 2010. The
      expression of PD-L1 was examined on the tumor cells and the tumor surrounding
      tissue by immunohistochemistry. An expression of >1% was considered as positive.
      Statistical analysis was performed to determine significant predictors for
      survival. RESULTS: 56 of 76 patients with LCNEC were treated with a potentially
      therapeutic surgical approach. Tumor-specific survival (TSS) of the entire cohort
      was 29% at five years. 17 patients (22.3%) had PD-L1 positive tumors and 12 of
      these had no additional PD-L1 expression in the adjacent immune cell infiltrate.
      Tumor-flanking immune cells were found PD-L1 positive 28 patients; 16 of these
      had no additional expression on the tumor cells. The most considerable difference
      in survival was found when comparing patients with isolated PD-L1 expression on
      tumor cells and PD-L1 negative immune cell infiltrate to their counterpart
      (positive immune-cell infiltrate and PD-L1 negative tumor cell surface; 5-year
      TSS: 0% vs. 60%; p < 0.017). CONCLUSION: PD-L1 expression in LCNEC was associated
      with poorer survival whereas PD-L1 expression in the tumor microenvironment
      seemed to have a beneficial effect. Therapeutic approaches have to be evaluated
      in future.

PMID- 29572008
TI  - What CT characteristics of lepidic predominant pattern lung adenocarcinomas
      correlate with invasiveness on pathology?
AB  - OBJECTIVES: The International Association for the Study of Lung Cancer, American
      Thoracic Society and European Respiratory Society lung adenocarcinoma
      classification in 2011 defined three lepidic predominant patterns including
      adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant
      adenocarcinoma. We sought to correlate the radiology and pathology findings and
      identify any computed tomography (CT) features which can be associated with
      invasive growth. MATERIALS AND METHODS: An institutional review board approved,
      retrospective study was conducted evaluating 63 patients with resected,
      pathologically confirmed, adenocarcinomas with predominant lepidic patterns.
      Preoperative CT images of the nodules were assessed using quantitative and
      qualitative radiographic descriptors while blinded to pathologic sub
      classification and size. Maximum diameter was measured after evaluation of the
      axial, sagittal and coronal planes. Radiologic - pathologic associations were
      examined using Fisher's exact test, the Kruskal-Wallis test and the Spearman
      correlation coefficient (rho). RESULTS AND CONCLUSION: Increasing maximum
      diameter of the whole lesion (ground glass and solid component) on CT was
      significantly associated with invasiveness (p = .003), as was the maximum
      pathologic specimen diameter (p = .008). Larger diameter of the solid component
      on CT was also found in lepidic predominant adenocarcinoma compared to minimally
      invasive adenocarcinoma (median 10.5 vs 2 mm, p = .005). More invasive tumors had
      higher visual estimated percentage solid component compared to whole lesion
      measurement on CT (p = .014). CT and pathologic measurements were positively
      correlated, although only moderately (rho = .66) for the maximum whole lesion
      size and fair (rho = .49) for solid/invasive component maximum measurements.
      Larger whole lesion size and solid component size of lepidic predominant pattern
      adenocarcinomas are associated with lesion invasiveness, although radiologic and
      pathologic lesion measurements are only fair-moderately positively correlated.

PMID- 29572009
TI  - Combined effect of ERCC1 and ERCC2 polymorphisms on overall survival in non
      squamous non-small-cell lung cancer patients treated with first-line
      pemetrexed/platinum.
AB  - OBJECTIVES: Polymorphisms of DNA repair genes may affect DNA repair capacity and
      the sensitivity of platinum doublets chemotherapy in non-small-cell lung cancer
      (NSCLC). We prospectively evaluated whether single nucleotide polymorphisms
      (SNPs) of ERCC1, ERCC2, XRCC1, and XRCC3 were associated with treatment outcome
      in advanced non-squamous NSCLC patients receiving pemetrexed/platinum as their
      first-line chemotherapy. MATERIALS AND METHODS: Genotyping of six SNPs in four
      DNA repair genes in 58 patients treated with first-line pemetrexed/platinum was
      performed using TaqMan SNP Genotyping Assays. RESULTS: The wild-type ERCC1 8092
      (C/C) was significantly associated with a better objective response compared to
      the variant genotypes (C/A + A/A) (48% vs 10%, P = .005). In the multivariate Cox
      proportional hazards model, we found that individuals with a wild-type genotype
      of ERCC1 Asn118Asn, ERCC1 C8092A and ERCC2 Asp312Asn had significantly better
      overall survival (OS) than those with a heterozygous or homozygous variant
      genotype. On the other hand, the heterozygous variant genotype of ERCC2 Lys751Gln
      was associated with better OS than that of the wild-type genotype. We further
      explored the combined effect of SNPs on OS, and found a significant allele/dose
      dependent trend toward decreasing OS in patients with an increasing number of
      unfavorable alleles among four SNPs in ERCC1 and ERCC2. The median OS of patients
      with two or three unfavorable alleles (30.1 and 30.5 months, respectively) was
      significantly longer than that of patients with 4 unfavorable alleles (11.8
      months, log-rank test for trend, P = .001). CONCLUSION: A combination of ERCC1
      and ERCC2 polymorphisms may predict OS among pemetrexed/platinum treated advanced
      non-squamous NSCLC patients.

PMID- 29572010
TI  - Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly
      correlated with prognosis.
AB  - OBJECTIVES: Ceruloplasmin (CP) is a well-known copper binding protein synthesized
      mainly in the liver, but its expression is known to be elevated in the serum of
      cancer patients and in malignant tumor cells. Lung cancer is the leading cause of
      cancer-related death worldwide, and adenocarcinoma is the main histological type
      of lung cancer. However, the role of CP in lung adenocarcinoma is still unclear.
      Here we examined and compared the expression of CP in various histological
      subtypes of lung adenocarcinoma and its correlation with clinicopathological
      parameters. MATERIALS AND METHODS: We examined CP expression in lung
      adenocarcinoma samples and cell lines using quantitative real-time RT-PCR and
      Western blot analysis. Immunohistochemistry for CP was carried out using 196
      specimens of lung adenocarcinoma. RESULTS: CP expression was significantly higher
      in invasive adenocarcinoma than in adenocarcinoma in situ (AIS), and was
      significantly correlated with poorer outcome, pathological stage, pT, and pN.
      Multivariate analysis showed that CP expression was an independent prognostic
      factor for lung adenocarcinoma patients. Furthermore, Western blot analysis using
      protein extracted from lung adenocarcinoma cell lines revealed the secreted form
      of CP. CONCLUSION: CP is produced heterotopically in lung adenocarcinoma cells
      and its expression is associated with tumor progression. In view of the presence
      of the secreted form of CP in tumor cells, CP may be a useful biomarker for lung
      adenocarcinoma.

PMID- 29572012
TI  - Effects of paeoniflorin on neurobehavior, oxidative stress, brain insulin
      signaling, and synaptic alterations in intracerebroventricular streptozotocin
      induced cognitive impairment in mice.
AB  - Paeoniflorin (PF) is a natural monoterpene glycoside in Paeonia lactiflora pall
      with anti-diabetic, antioxidant, anti-inflammatory, and neuro-protective
      properties. This study was designed to investigate the neuroprotective effects of
      PF against cognitive deficits induced by intracerebroventricular (ICV) injection
      of streptozotocin (STZ) in mice. STZ was injected twice intracerebroventrically
      (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with
      PF (10 mg/kg per day, intraperitoneally) starting from the first dose of STZ for
      21 days showed an improvement in ICV-STZ induced cognitive deficits as assessed
      by novel object recognition and Morris water maze (MWM) test. PF significantly
      attenuated STZ induced mitochondrial dysfunction manifested by dramatically
      elevated cytochrome c oxidase activity and ATP synthesis, and restoration of the
      mitochondrial membrane potential (MMP), and oxidative stress in hippocampus and
      in the cortex compared to control. Moreover, PF treatment also markedly increased
      synaptic density in the CA1 region of the hippocampus compared to control.
      Furthermore, PF ameliorated defective insulin signaling by up-regulating p-PI3K
      and p-Akt protein expression while downregulating p-IRS-1 protein expression.
      Taken together, the outcomes of the current study suggest the therapeutic
      potential of PF in the cognitive deficits induced by ICV-STZ.

PMID- 29572011
TI  - Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic
      biomarker.
AB  - Despite all the advances in diagnosis and treatment of breast cancer, a large
      number of patients suffer from late diagnosis or recurrence of their disease.
      Current available imaging modalities do not reveal micrometastasis and tumor
      biopsy is an invasive method to detect early stage or recurrent cancer,
      signifying the need for an inexpensive, non-invasive diagnostic modality. Cell
      free tumor DNA (ctDNA) has been tried for early detection and targeted therapy of
      breast cancer, but its diagnostic and prognostic utility is still under
      investigation. This review summarizes the existing evidence on the use of ctDNA
      specifically in breast cancer, including detection methods, diagnostic accuracy,
      role in genetics and epigenetics evaluation of the tumor, and comparison with
      other biomarkers. Current evidence suggests that increasing levels of ctDNA in
      breast cancer can be of significant diagnostic value for early detection of
      breast cancer although the sensitivity and specificity of the methods is still
      suboptimal. Additionally, ctDNA allows for characterizing the tumor in a non
      invasive way and monitor the response to therapy, although discordance of ctDNA
      results with direct biopsy (i.e. due to tumor heterogeneity) is still considered
      a notable limitation.

PMID- 29572013
TI  - Nicotine emissions from electronic cigarettes: Individual and interactive effects
      of propylene glycol to vegetable glycerin composition and device power output.
AB  - INTRODUCTION: The power output of e-cigarettes varies considerably, as does the
      composition of liquids used with these products. Most e-cigarette liquids contain
      two primary solvents: propylene glycol (PG) and vegetable glycerin (VG). The
      primary aim of this study was to examine the extent to which PG and VG
      composition and device power interact with each other to influence e-cigarette
      nicotine emissions. METHODS: Aerosols were generated using a 2nd generation e
      cigarette and an automatic smoking machine. Nicotine was measured in aerosols,
      via gas chromatography, produced from three solutions containing pure PG, pure
      VG, or a mixture of both solvents (50:50) across three different power settings
      (4.3, 6.7, and 9.6 W). RESULTS: At the lowest power setting, nicotine yield
      increased significantly as more PG was added to the solution. However, as device
      power was increased, differences in nicotine yield across liquids became less
      pronounced. At the highest power setting (9.6 W), nicotine yields did not differ
      across the three liquids examined. CONCLUSIONS: The present study demonstrated
      that the extent to which e-cigarette liquid PG and VG composition influences
      nicotine emissions is dependent on device power. Thus, device power may influence
      e-cigarette nicotine emissions to a greater degree relative to solvent
      concentrations.

PMID- 29572014
TI  - Anticonvulsants lamotrigine and riluzole disrupt maternal behavior in postpartum
      female rats.
AB  - Maternal behavior is a highly motivated and well-organized social behavior.
      Previous studies have reported that anticonvulsants are frequently used in
      postpartum bipolar disorder. However, the maternal disruptive effect of the
      anticonvulsants has not been explored. The purpose of the present study was to
      examine the effect of anticonvulsants lamotrigine and riluzole on maternal
      behavior in postpartum female rats. On postpartum Day 3, Sprague-Dawley mother
      rats were given a single intraperitoneal injection of vehicle, lamotrigine (15,
      25, 35 mg/kg), or riluzole (2, 4, 8 mg/kg). Maternal behavior was tested 30 min
      before and after injection. Animals treated with lamotrigine or riluzole had a
      longer pup retrieval latency, retrieved fewer pups into the nest, spent less time
      on nursing pups, as well as on building the disturbed nest, and animals treated
      with riluzole spent less time on pup licking. Whereas, the drugs in the tested
      doses did not shorten the total duration of behavior unrelated to maternal
      behavior. Overall, these data indicate that lamotrigine and riluzole disrupt
      major components of maternal behavior in postpartum female rats, but do not
      inhibit the behaviors unrelated to maternal behavior, which indicates that the
      maternal disruptive effect is not due to nonspecific sedative effect.

PMID- 29572015
TI  - Differential effects of single versus repeated minocycline administration-Lack of
      significant interaction with chronic alcohol history.
AB  - Neuroimmune cytokines are increased with alcohol withdrawal and may mediate
      clinical responses associated with alcoholism. Because minocycline regulates the
      level of cytokines, it has been suggested as a therapeutic for disorders
      associated with alcohol. Male Wistar rats were exposed to chronic intermittent
      alcohol (CIA) comprising three 5-day cycles of ethanol liquid diet separated by 2
      days of withdrawal. Rats were tested on social interaction, a measure of anxiety
      like behavior, followed immediately by collection of amygdala tissue to measure
      CCL2 and TNFalpha or collection of the blood to measure corticosterone (CORT).
      One group received a single minocycline injection 3 h into the final CIA
      withdrawal and was tested 2 h later. A second group received injections during
      each of the three withdrawals and was similarly tested during the final acute
      withdrawal. A third group received a single injection at 23 h into withdrawal
      (extended withdrawal) and was tested 6 h later. Results showed that CIA
      withdrawal increased anxiety-like behavior. A single injection of minocycline
      during the final acute withdrawal increased anxiety-like behavior in rats that
      consumed liquid diet with or without alcohol, but this effect disappeared with
      repeated injections of minocycline. Differences in alcohol intake, blood alcohol
      level, and plasma CORT levels did not explain results. Only repeated injections
      of minocycline decreased TNFalpha mRNA levels in rats that consumed liquid diet
      with or without alcohol. When a single injection of minocycline was given during
      extended withdrawal, it decreased CCL2 mRNA levels, but did not reverse the
      elevation of CCL2 protein. These results suggest that minocycline has actions in
      brain and on behavior, but minocycline does not significantly impact these
      actions in relation to alcohol withdrawal.

PMID- 29572016
TI  - Outcomes of Radiofrequency Ablation Therapy for Large Benign Thyroid Nodules: A
      Mayo Clinic Case Series.
AB  - OBJECTIVE: To assess the effectiveness, tolerability, and complications of
      radiofrequency ablation (RFA) in patients with benign large thyroid nodules
      (TNs). PATIENTS AND METHODS: This is a retrospective review of 14 patients with
      predominantly solid TNs treated with RFA at Mayo Clinic in Rochester, Minnesota,
      from December 1, 2013, through October 30, 2016. All the patients declined
      surgery or were poor surgical candidates. The TNs were benign on fine-needle
      aspiration, enlarging or causing compressive symptoms, and 3 cm or larger in
      largest diameter. We evaluated TN volume, compressive symptoms, cosmetic
      concerns, and thyroid function. RESULTS: Median TN volume reduction induced by
      RFA was 44.6% (interquartile range [IQR], 42.1%-59.3%), from 24.2 mL (IQR, 17.7
      42.5 mL) to 14.4 mL (IQR, 7.1-19.2 mL) (P<.001). Median follow-up was 8.6 months
      (IQR, 3.9-13.9 months). Maximum results were achieved by 6 months. Radiofrequency
      ablation did not affect thyroid function. In 1 patient with subclinical
      hyperthyroidism due to toxic adenoma, thyroid function normalized 4 months after
      ablation of the toxic nodule. Compressive symptoms resolved in 8 of 12 patients
      (67%) and improved in the other 4 (33%). Cosmetic concerns improved in all 8
      patients. The procedure had no sustained complications. CONCLUSION: In this
      population, RFA of benign large TNs performed similarly to the reports from
      Europe and Asia. It induces a substantial volume reduction of predominantly solid
      TNs, improves compressive symptoms and cosmetic concerns, and does not affect
      normal thyroid function. Radiofrequency ablation has an acceptable safety profile
      and should be considered as a low-risk alternative to conventional treatment of
      symptomatic benign TNs.

PMID- 29572017
TI  - The view of experts on initiatives to be undertaken to promote equity in the
      access to orphan drugs and specialised care for rare diseases in Spain: A Delphi
      consensus.
AB  - OBJECTIVES: To reach a consensus amongst experts on the most feasible actions to
      be undertaken to facilitate patient access to specialised care and orphan drugs
      (OD) in the public health sector in Spain. METHODS: Two Delphi rounds were
      completed. The questionnaire was based on a literature review and 2 focus groups.
      Agreement was sought on the desire (D) and prognosis (P) for the implementation
      within the next 5 years, on a 5-point Likert scale. Consensus was reached when
      >=75% participants chose agreement (1-2) or disagreement options (4-5). RESULTS:
      82 experts on rare disease (RD) participated. Agreement on the D and P was
      reached in 66.07% statements: OD pricing review [absence of clinical
      effectiveness (D:85.37%; P:85.90%), target population increase (D:79.27%;
      P:91.03%)]; reference team definition of referral protocols and clinical practice
      guidelines (D: 97.56%; P: 89.74%); and a unified, usable, etiology-based registry
      (D:97.56%; P:84.62%). D and P assessment diverged in 32.14% items: creation of a
      specific funding system for OD (D: 97.56%; P: 60.25%); and a network of medical
      teams to coordinate the care of RD patients (D: 99%; P: 62%). CONCLUSIONS: The
      results have shown the need to promote dialogue between stakeholders, introduce
      European recommendation to national and regional Spanish policies and set up
      priorities and undertake actions to drive relevant changes in current medical
      practice in managing RD patients.

PMID- 29572018
TI  - Strategies for newborn screening for cystic fibrosis: A systematic review of
      health economic evaluations.
AB  - BACKGROUND: Early detection of cystic fibrosis through newborn screening has
      significant clinical benefits. Cost-effectiveness plays an important role in
      selecting the optimal screening strategy from the many available options.
      OBJECTIVES: The objectives of this study are (1) to summarize study estimates of
      cost-effectiveness of cystic fibrosis newborn screening (CFNBS) strategies as
      compared to other strategies, (2) to assess the quality of the studies
      identified, and (3) to identify determinants of cost-effectiveness. METHODS:
      Electronic databases were searched from 2007 to June 2017. Health economic
      evaluations describing the cost-effectiveness of two or more CFNBS strategies
      were included. RESULTS: Six health economic evaluations were found. Where
      included in the comparison, IRT/PAP consistently was the most cost-effective
      strategy in terms of cost per case detected or life years gained. However, some
      heterogeneity with respect to cut-off values used and the number of DNA mutations
      included in the screening strategies was observed, and the methodological quality
      differed considerably between studies. CONCLUSIONS: The evidence suggested that
      (i) all screening strategies are cost-effective as compared to the no-screening
      option and (ii) IRT-PAP seems to be the most cost-effective screening strategy
      towards CFNBS. Methodological and contextual differences of the individual
      studies make it difficult to derive strong conclusions from this evidence.
      Nevertheless, from a health-economic perspective, IRT-PAP should be included as
      an alternative when deciding on the screening strategy in the implementation of
      CFNBS.

PMID- 29572019
TI  - Oops, I injured the internal thoracic artery! Never mind?

PMID- 29572020
TI  - The genetics of bicuspid aortic valve disease: Shall we take it down a NOTCH?

PMID- 29572022
TI  - Early fundoplication is associated with slower decline in lung function after
      lung transplantation in patients with gastroesophageal reflux disease.
AB  - OBJECTIVES: Gastroesophageal reflux disease (GERD) is prevalent after lung
      transplantation. Fundoplication slows lung function decline in patients with
      GERD, but the optimal timing of fundoplication is unknown. METHODS: We
      retrospectively reviewed patients who underwent fundoplication after lung
      transplantion at our center from April 2007 to July 2014. Patients were divided
      into 2 groups: early fundoplication (<6 months after lung transplantation) and
      late fundoplication (>=6 months after lung transplantation). Annual decline in
      percent predicted forced expiratory volume in 1 second (FEV1) was analyzed.
      RESULTS: Of the 251 patients who underwent lung transplantation during the study
      period with available pH data, 86 (34.3%) underwent post-transplantation
      fundoplication for GERD. Thirty of 86 (34.9%) had early fundoplication and 56 of
      86 (65.1%) had late fundoplication. Median time from lung transplantation to
      fundoplication was 4.6 months (interquartile range, 2.0-5.2) and 13.8 months
      (interquartile range, 9.0-16.1) for the early and late groups, respectively. The
      median DeMeester score was comparable between groups. One-, 3-, and 5-year
      actuarial survival rates in the early group were 90%, 70%, and 70%, respectively;
      in the late group, these rates were 91%, 66%, and 66% (log rank P = .60). Three-
      and 5-year percent predicted FEV1 was lower in the late group by 8.9% (95%
      confidence interval, -30.2 to 12.38; P = .46) and 40.7% (95% confidence interval,
      -73.66 to -7.69; P = .019). A linear mixed model showed a 5.7% lower percent
      predicted FEV1 over time in the late fundoplication group (P < .001).
      CONCLUSIONS: In this study, patients with early fundoplication had a higher FEV1
      5 years after lung transplantation. Early fundoplication might protect against
      GERD-induced lung damage in lung transplant recipients with GERD.

PMID- 29572023
TI  - Life with limb instead limb for life-selective perfusion safes extremities.

PMID- 29572021
TI  - A novel tissue treatment to reduce mineralization of bovine pericardial heart
      valves.
AB  - OBJECTIVE: With the increasing use of bioprostheses worldwide, continuous efforts
      have been made to improve tissue durability. We introduce a new treatment for
      bovine pericardium combining octanediol-ethanol based phospholipid removal with
      taurine-based glutaraldehyde neutralization and storage in an aldehyde-free
      solution (FREE). METHODS: Treated tissues were evaluated by mechanical and
      biochemical characterization, phospholipid content, aldehyde levels, cell
      cultures on pericardial samples (L929 fibroblasts and human umbilical vein
      endothelial cells), rat subcutaneous implantations, and long-term juvenile sheep
      mitral valve implantations (n = 3). Comparisons were made to glutaraldehyde-fixed
      bovine pericardium or to samples from commercially available biological valves
      (ie, Trifecta [St Jude Medical, Saint Paul, Minn] and Perimount Magna Ease
      [Edwards Lifesciences, Irvine, Calif]). RESULTS: FREE-treated pericardium had
      similar mechanical strength and biochemical properties as commercially available
      valves. Compared with glutaraldehyde-only samples, FREE-treated samples showed
      lower phospholipid levels (P < .01), significantly better growth of L929
      fibroblasts, and lower calcification levels in rat subcutaneous implants (P <
      .01). Compared with samples from Linx- (Trifecta) and ThermaFix-treated
      (Perimount Magna Ease) valves, similar low levels of phospholipids were observed
      as were similar low calcification levels in subcutaneous implants, but tissue
      extractions from FREE-treated samples showed the lowest levels of extracted
      aldehydes (P < .01). Mitral implants of FREE-treated valves in juvenile sheep had
      excellent hemodynamic behavior without any sign of degeneration or calcification
      at 5 months. CONCLUSIONS: The new FREE treatment combines an adequate
      phospholipid reduction and aldehyde neutralization with storage in an aldehyde
      free solution. This combination enhances the anticalcification properties and may
      thereby improve long-term durability of the tissue.

PMID- 29572024
TI  - A unique computed tomographic finding: Dissection? Congenital structure?
      Artifact? New entity?-Significance in diagnosis of the "intra-aortic chord".

PMID- 29572025
TI  - Closure of the sternum with anchoring of the steel wires: Systematic review and
      meta-analysis.

PMID- 29572026
TI  - Going the extra mile.

PMID- 29572028
TI  - Back to the future - The integration of big data with machine learning is re
      establishing the importance of predictive correlations in ovarian cancer
      diagnostics and therapeutics.

PMID- 29572027
TI  - A novel multiple biomarker panel for the early detection of high-grade serous
      ovarian carcinoma.
AB  - INTRODUCTION: Since the majority of patients are diagnosed at an advanced stage,
      ovarian cancer remains the most lethal gynecologic malignancy. There is no single
      biomarker with the sensitivity and specificity required for effective cancer
      screening; therefore, we investigated a panel of novel biomarkers for the early
      detection of high-grade serous ovarian carcinoma. METHODS: Twelve serum
      biomarkers with high differential gene expression and validated antibodies were
      selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN,
      and OPN. They were tested using Simple PlexTM, a multi-analyte immunoassay
      platform, in samples collected from 172 patients who were either healthy, had
      benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas.
      The receiver operating characteristic (ROC) curve, ROC area under the curve
      (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses
      and multivariate ROC analyses with the combination of multiple biomarkers were
      performed. RESULTS: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6
      had the highest ROC AUC. When evaluated for the ability to distinguish early
      stage ovarian cancer from a non-cancer control, not only did this 4-marker panel
      (AUC=0.961) performed better than CA 125 alone (AUC=0.851; P=0.0150) and HE4
      alone (AUC=0.870; P=0.0220), but also performed significantly better than the 2-
      marker combination of CA125+HE4 (AUC=0.922; P=0.0278). The 4-marker panel had the
      highest average sensitivity under the region of its ROC curve corresponding to
      specificity ranging from 100% down to ~95%. CONCLUSION: The four-marker panel,
      CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer
      at earlier stages. Additional validation studies using the biomarker combination
      in ovarian cancer patients are warranted.

PMID- 29572029
TI  - Prognostic implication of programmed cell death 1 protein and its ligand
      expressions in endometrial cancer.
AB  - OBJECTIVE: Monoclonal antibodies targeting programmed cell death-1 (PD
      1)/programmed death ligand 1 (PD-L1) demonstrated promising clinical response.
      The predictive/prognostic value of PD-1/PD-L1 immunohistochemistry (IHC) has been
      evaluated in many cancer types. However, the prognostic value of PD-1/PD-L1 IHC
      has not been evaluated in endometrial cancer. METHODS: We conducted a
      retrospective study to quantify the IHC CD8, PD-1, and PD-L1 expressions in
      immune cells at center of tumor (CT), invasive margin (IM), and/or tumor cell in
      183 primary endometrial cancer samples from a single cohort, followed by their
      reciprocal combinations, including compartmental differences, and correlated them
      with overall survival (OS) and progression-free survival (PFS). RESULTS: In
      repeated Cox multivariable models adjusted by clinicoimmunopathologic factors,
      high CT-PD-L1 was an independent adverse prognostic factor for PFS in all
      patients and in the microsatellite-stable subgroup. Immune marker ratios revealed
      independently shorter PFS for high CT-PD-L1/CT-CD8 and CT-PD-L1/CT-PD-1 ratios.
      Classification of endometrial cancer into four groups based on CT-CD8 and CT-PD
      L1 revealed significantly different survival among groups. CONCLUSIONS: The high
      PD-L1/CD8 ratio and the high expression of PD-L1 on immune cells were independent
      poor prognostic factors for PFS in endometrial cancer, providing insights into
      the tumor microenvironment.

PMID- 29572030
TI  - Integrated analysis of HPV-mediated immune alterations in cervical cancer.
AB  - OBJECTIVE: Human papillomavirus (HPV) infection is the primary cause of cervical
      cancer. HPV-mediated immune alterations are known to play crucial roles in
      determining viral persistence and host cell transformation. We sought to
      thoroughly understand HPV-directed immune alterations in cervical cancer by
      exploring publically available datasets. METHODS: 130 HPV positive and 7 HPV
      negative cervical cancer cases from The Cancer Genome Atlas were compared for
      differences in gene expression levels and functional enrichment. Analyses for
      copy number variation (CNV) and genetic mutation were conducted for
      differentially expressed immune genes. Kaplan-Meier analysis was performed to
      assess survival and relapse differences across cases with or without alterations
      of the identified immune signature genes. RESULTS: Genes up-regulated in HPV
      positive cervical cancer were enriched for various gene ontology terms of immune
      processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially
      expressed immune genes identified 9 genes that displayed either CNV, genetic
      mutation and/or gene expression changes in at least 10% of the cases of HPV
      positive cervical cancer. Genomic amplification may cause elevated levels of
      these genes in some HPV positive cases. Finally, patients with alterations in at
      least one of the nine signature genes overall had earlier relapse compared to
      those without any alterations. The altered expression of either TFRC or MMP13 may
      indicate poor survival for a subset of cervical cancer patients (P=1.07E-07).
      CONCLUSIONS: We identified a novel immune gene signature for HPV positive
      cervical cancer that is potentially associated with early relapse of cervical
      cancer.

PMID- 29572031
TI  - Helicase POLQ-like (HELQ) as a novel indicator of platinum-based chemoresistance
      for epithelial ovarian cancer.
AB  - OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial
      ovarian carcinoma (EOC), which is a critical factor of patients' prognosis.
      METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and
      bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011)
      disclosed the clinical importance of HELQ expression. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of
      EOC tissue were used to confirm it. Ectopic overexpression and RNA interference
      knockdown of HELQ were carried out in OVCAR3 and A2780 cell lines, respectively,
      to determine the effect of altered HELQ expression on cellular response to
      cisplatin by CCK8 assay. The DNA repair capacity of these cells was evaluated by
      using host-cell reactivation assay. Western Blot analyses were carried out to
      determine the effect of HLEQ on the DNA repair genes by using cells with altered
      HELQ expression. RESULTS: HELQ expression associates with response of EOC
      patients to platinum-based chemotherapy and their overall survival (OS), disease
      free survival (DFS). HELQ overexpression or knockdown, respectively, increased
      and decreased the cellular resistance to cisplatin, DNA repair activity, and
      expression of DNA repair proteins of Nucleotide excision repair (NER) pathway.
      CONCLUSIONS: HELQ plays an important role in regulating the expression of DNA
      repair proteins NER pathway which, in turn, contributes to cellular response to
      cisplatin and patients' response to platinum-based chemotherapy. Our results
      demonstrated that HELQ could serve as a novel indicator for chemo-resistance of
      EOC, which can predict the prognosis of the disease.

PMID- 29572032
TI  - Chloride imbalance is involved in the pathogenesis of optic neuritis in
      neuromyelitis optica.
AB  - Chloride imbalance between the serum and the cerebrospinal fluid (CSF) has been
      recently shown to exist in the acute phase of neuromyelitis optica (NMO). In this
      report, we studied the relation between the quotient of chloride (QCl) and the
      severity of optic neuritis (ON) in NMO patients. There was a positive correlation
      (R = 0.67; p < 0.05) between QCl and the length of ON-lesion. The visual
      prognosis also showed a positive correlation with QCl in the acute phase (R =
      0.58; p < 0.05). These results support the theory that chloride imbalance between
      serum and CSF may trigger the ON in NMO spectrum disorders.

PMID- 29572033
TI  - Role of the cell membrane interface in modulating production and uptake of
      Alzheimer's beta amyloid protein.
AB  - The beta amyloid protein (Abeta) plays a central role in Alzheimer's disease (AD)
      pathogenesis and its interaction with cell membranes in known to promote mutually
      disruptive structural perturbations that contribute to amyloid deposition and
      neurodegeneration in the brain. In addition to protein aggregation at the
      membrane interface and disruption of membrane integrity, growing reports
      demonstrate an important role for the membrane in modulating Abeta production and
      uptake into cells. The aim of this review is to highlight and summarize recent
      literature that have contributed insight into the implications of altered
      membrane composition on amyloid precursor protein (APP) proteolysis, production
      of Abeta, its internalization in to cells via permeabilization and receptor
      mediated uptake. Here, we also review the various membrane model systems and
      experimental tools used for probing Abeta-membrane interactions to investigate
      the key mechanistic aspects underlying the accumulation and toxicity of Abeta in
      AD.

PMID- 29572034
TI  - Solubilization kinetics determines the pulsatory dynamics of lipid vesicles
      exposed to surfactant.
AB  - We establish a biophysical model for the dynamics of lipid vesicles exposed to
      surfactants. The solubilization of the lipid membrane due to the insertion of
      surfactant molecules induces a reduction of membrane surface area at almost
      constant vesicle volume. This results in a rate-dependent increase of membrane
      tension and leads to the opening of a micron-sized pore. We show that
      solubilization kinetics due to surfactants can determine the regime of pore
      dynamics: either the pores open and reseal within a second (short-lived pore), or
      the pore stays open up to a few minutes (long-lived pore). First, we validate our
      model with previously published experimental measurements of pore dynamics. Then,
      we investigate how the solubilization kinetics and membrane properties affect the
      dynamics of the pore and construct a phase diagram for short and long-lived
      pores. Finally, we examine the dynamics of sequential pore openings and show that
      cyclic short-lived pores occur with a period inversely proportional to the
      solubilization rate. By deriving a theoretical expression for the cycle period,
      we provide an analytical tool to estimate the solubilization rate of lipid
      vesicles by surfactants. Our findings shed light on some fundamental biophysical
      mechanisms that allow simple cell-like structures to sustain their integrity
      against environmental stresses, and have the potential to aid the design of
      vesicle-based drug delivery systems. This article is part of a Special Issue
      entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo.

PMID- 29572035
TI  - The Emerging Role of 3D Printing in Arthroplasty and Orthopedics.
AB  - This article reviews the emerging role of 3D printing in arthroplasty and
      orthopedics, a topic of growing relevancy. It discusses the evolution of the
      technology, the value offered by the technology, current trends and factors
      impacting adoption in orthopedics, and areas of current and potential future use
      in arthroplasty and orthopedics.

PMID- 29572036
TI  - Predictors of Treatment Failure After 2-Stage Reimplantation for Infected Total
      Knee Arthroplasty: A 2- to 10-Year Follow-Up.
AB  - BACKGROUND: The aim of this study is to identify risk factors which may lead to
      treatment failure following 2-stage reimplantation for chronic infected total
      knee arthroplasty (TKA). METHODS: We retrospectively reviewed 106 patients (108
      knees) who underwent consecutive 2-stage revision for chronic PJI of the knee at
      our institution between January 2005 and December 2015. A total of 31 risk
      factors, including patient characteristics, comorbidities, surgical variables,
      and microbiology data, were collected. Kaplan-Meier survival and Cox regression
      analyses were used to calculate survival rates and adjusted hazard ratios (HRs)
      of treatment failure. RESULTS: Within the cohort, 16 of the 108 2-stage
      reimplantations (14.8%) had treatment failure. The treatment success for 2-stage
      reimplantation was 91% (95% confidence interval [CI] 0.8-1.0) at 2 years and 84%
      (95% CI 0.8-0.9) at 5 and 10 years. Multivariate analysis provided the strongest
      predictors of treatment failure, including body mass index >=30 kg/m2 (adjusted
      HR 9.3, 95% CI 2.7-31.8, P < .001), operative time >4 hours (adjusted HR 11.3,
      95% CI 3.9-33.1, P < .001), gout (adjusted HR 13.8, 95% CI 2.9-66.1, P = .001),
      and the presence of Enterococcus species during resection arthroplasty (adjusted
      HR 14.1, 95% CI 2.6-76.3, P = .002). CONCLUSION: Our study identified 4 potential
      risk factors that may predict treatment failure following 2-stage revision for
      chronic knee PJI. This finding may be useful when counseling patients regarding
      the treatment success and prognosis of 2-stage reimplantation for infected TKA.

PMID- 29572037
TI  - Prognostic Factors for Success After Irrigation and Debridement With Modular
      Component Exchange for Infected Total Knee Arthroplasty.
AB  - BACKGROUND: Irrigation and debridement with modular component exchange (IDMCE)
      can treat prosthetic joint infection (PJI) after total knee arthroplasty (TKA).
      Compared to 2-stage revision, IDMCE is associated with lower morbidity but may
      carry higher infection recurrence rates. We aimed to identify prognostic factors
      associated with successful IDMCE in patients with PJI. METHODS: We identified 99
      consecutive patients who underwent IDMCE following TKA PJI at a tertiary academic
      medical center from November 2009 through January 2016. Examined variables
      included age, gender, symptom duration, body mass index, Charlson comorbidity
      index, total protein, albumin, hemoglobin A1c, erythrocyte sedimentation rate
      (ESR), C-reactive protein, white blood cell count, gram stain results, final
      cultures, and use of long-term antibiotic suppression. Success was defined as no
      further operation on the ipsilateral knee. We used t tests and chi-square
      analyses to determine whether each preoperative factor was associated with IDMCE
      reoperation. RESULTS: At mean follow-up of 2.6 years, 64 patients who underwent
      IDMCE were defined as successful. Thirty-five patients required one or more
      additional procedures for recurrent infection; of these, 20 patients underwent 2
      stage revision. Patients with symptom duration of less than 2 days avoided
      additional surgery in 88% of cases. Elevated ESR >47 mm/h was the only variable
      associated with reoperation (P = .005). There were no associations among the
      other examined variables. CONCLUSION: Using IDMCE for PJI after TKA required
      reoperation in 35% of cases. Elevated preoperative ESR laboratory values and
      duration of symptoms >2 days were associated with reoperation.

PMID- 29572038
TI  - High Efficiency Particulate Air Filters Do Not Affect Acute Infection Rates
      During Primary Total Joint Arthroplasty Using Forced Air Warmers.
AB  - BACKGROUND: Studies have suggested that forced-air warmers (FAWs) increase
      contamination of the surgical site. In response, FAWs with high efficiency
      particulate air filters (FAW-HEPA) were introduced. This study compared infection
      rates following primary total joint arthroplasty (TJA) using FAW and FAW-HEPA.
      METHODS: Primary TJA patients at a single healthcare system were retrospectively
      reviewed. A total of 5405 THA (n = 2419) and TKA (n = 2986) consecutive cases in
      2013 and 2015 were identified. Patients in 2013 (n = 2792) had procedures using
      FAW, while FAW-HEPA was used in 2015 (n = 2613). The primary outcome was overall
      infection rate within 90-days. Sub-categorization of infections as periprosthetic
      joint infection (PJI) or surgical site infection (SSI) was also conducted. PJI
      was defined as reoperation with arthrotomy or meeting Musculoskeletal Infection
      Society (MSIS) criteria. SSI was defined as wound complications requiring
      antibiotics or irrigation/debridement. RESULTS: The FAW and FAW-HEPA groups had
      similar rates of overall infection (1.65% [n = 46] vs 1.61% [n = 42], P > .99),
      SSI (1.18% [n = 33] vs 0.84% [n = 22], P = .27), and PJI (0.47% [n = 13] vs 0.77%
      [n = 20], P = .22). Regression models did not show FAW to be an independent risk
      factor for increased overall infection (odds ratio [OR] 1.00, 95% confidence
      interval [CI] 0.65-1.57, P = .97), SSI (OR 1.47, 95% CI 0.83-2.58, P = .18), or
      PJI (OR 0.53, 95% CI 0.25-1.13, P = .09). CONCLUSION: FAW were not correlated
      with a higher risk of overall infection, SSI, or PJI during TJA when compared to
      FAW-HEPA devices.

PMID- 29572039
TI  - Blood zinc levels and cognitive and functional evaluation in non-demented older
      patients.
AB  - A complete battery of geriatric and psychometric tests was used to determine
      whether plasma-borne zinc (Zn), a key ion in neuroplasticity, can be associated
      with the severity of functional, psychological and cognitive impairment in non
      demented older individuals. There was a significant positive correlation between
      plasma Zn levels and the concentration subcategory measured with the Mini-Mental
      State Examination (MMSE) test (p < 0.001), but not the total MMSE score, and the
      levels were significantly reduced in polymedicated patients (defined as
      concurrent administration of >5 drugs). No correlations were found between plasma
      Zn levels and depressive symptoms measured with the Yesavage scale for geriatric
      depression or the Barthel Index - a measurement of the ability of individuals to
      perform the activities of daily living. Depressive symptoms were associated with
      poor sleep quality and polymedication (p < 0.001 and p < 0.05, respectively). Our
      results suggest that peripheral Zn concentration may play a role in the
      physiopathology of some domain of cognitive function. No correlation to
      depressive symptoms in the geriatric population under antidepressant drug
      treatment was observed. However, further studies are needed to understand the
      relationship between circulating Zn and concentration deficits in order to
      determine whether Zn represents a candidate early biomarker for cognitive
      impairment.

PMID- 29572040
TI  - Fracture-dislocation of the proximal interphalangeal joint of the long fingers:
      Report of an unusual case requiring open surgery.
AB  - Dorsal fracture-dislocations of the proximal interphalangeal (PIP) joint of the
      long fingers are in most cases unstable. They require surgery, whose primary aim
      is to restore and maintain articular congruency. While numerous techniques exist
      to treat these injuries, none have been shown to be superior to any of the others
      in terms of outcomes and complications. The least invasive techniques should be
      used as much as possible. We report here a rare case of incarceration of the
      flexor tendons in the PIP fracture which required open surgery.

PMID- 29572041
TI  - Naloxone access for Emergency Medical Technicians: An evaluation of a training
      program in rural communities.
AB  - INTRODUCTION: Opioid-related overdose death rates in rural communities in the
      United States are much higher than their urban counterparts. However, basic life
      support (BLS) personnel, who are more common in rural areas, have much lower
      rates of naloxone administration than other levels of emergency medical services
      (EMS). Training and equipping basic level Emergency Medical Technician (EMTs) to
      administer naloxone for an opioid overdose could yield positive outcomes.
      METHODS: Following a legislative change that allowed EMTs to administer naloxone
      in one rural state, we evaluated an EMT training program by examining EMTs'
      opioid overdose knowledge and attitudes before and after the training. RESULTS:
      One-hundred-seventeen rural EMTs participated the training. They demonstrated
      statistically significant improvements on almost all of the knowledge questions
      after the training (p's = 0.0469 to <0.0001). The opioid overdose competency and
      concern scales showed statistically significant improvement (p < 0.0001) and
      reduction (p < 0.0001), respectively. Furthermore, statistically significant
      changes in knowledge and opinions of state law regarding naloxone administration
      were observed. Significantly more EMTs supported the idea of expanding naloxone
      to people at risk for overdose (p = 0.0026) after the training. CONCLUSIONS: At a
      time when states are passing legislation to expand first responders' access to
      naloxone, this study provides evidence about authorizing EMTs to administer
      naloxone.

PMID- 29572042
TI  - Population pharmacokinetics of daptomycin in critically ill patients.
AB  - Daptomycin has shown activity against a wide range of Gram-positive bacteria;
      however, the approved dosages usually seem insufficient for critically ill
      patients. The aim of this study was to develop a population pharmacokinetic model
      for daptomycin in critically ill patients and to estimate the success of the
      therapy by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. Sixteen
      intensive care unit patients were included, four of whom underwent continuous
      renal replacement therapies (CRRT). Blood and, when necessary, effluent samples
      were drawn after daptomycin administration at previously defined time points. A
      population approach using NONMEM 7.3 was performed to analyse data. Monte Carlo
      simulations were executed to evaluate the suitability of different dosage
      regimens. The probabilities of achieving the PK/PD target value associated with
      treatment success (ratio of the area under the plasma concentration-time curve
      over 24 h divided by the minimum inhibitory concentration (AUC24/MIC >= 666)) and
      to reach daptomycin concentrations linked to toxicity (minimum concentration at
      steady-state (Cminss) >= 24.3 mg/L) were calculated. The pharmacokinetics of
      daptomycin was best described by a one-compartment model. Elimination was
      conditioned by the creatinine clearance (Clcr) and also by the extra-corporeal
      clearance when patients were subjected to continuous renal replacement therapy
      (CRRT). The PK/PD analysis confirmed that 280- and 420-mg/d dosages would not be
      enough to achieve high probabilities of target attainment for MIC values >= 1
      mg/L in patients with Clcr >= 60 mL/min or in subjects with lower Clcrs but
      receiving CRRT. In these patients, higher dosages (560-840 mg/d) should be
      needed. When treating infections due to MIC values >= 4 mg/L, even the highest
      dose would be insufficient.

PMID- 29572043
TI  - Bioluminescence imaging increases in vivo screening efficiency for antifungal
      activity against device-associated Candida albicans biofilms.
AB  - Fungal infections are a major problem for a growing number of mostly
      immunocompromised patients. Candida albicans is an important human fungal
      pathogen causing mucosal and deep tissue infections, of which the majority are
      associated with biofilm formation on medical implants. Animal models that are
      currently in use to test antifungal drugs are limited to ex vivo analyses,
      requiring host sacrifice that excludes longitudinal monitoring of dynamic
      processes during biofilm formation in the live host. As a solution, we introduce
      non-invasive, dynamic imaging and quantification of C. albicans biofilm formation
      in vivo and subsequent evaluation of treatment efficacy against these biofilms
      using bioluminescent C. albicans in a catheter-associated mouse model.
      Bioluminescence imaging (BLI) allowed us to evaluate baseline biofilm load before
      the start of therapy, which is necessary for correct evaluation and
      interpretation of antibiofilm efficacy in vivo. Moreover, we demonstrate that
      this BLI approach monitors the antibiofilm activity of different antifungal
      agents efficiently in vitro and in vivo. In this study, BLI revealed superior
      antibiofilm activity for echinocandins compared with amphotericin B and
      fluconazole. In vitro, anidulafungin showed the highest antibiofilm activity,
      followed by micafungin and caspofungin. In vivo, caspofungin significantly
      decreased the biofilm fungal load, as documented by the lower BLI signal and
      confirmed by CFU counts. In conclusion, this BLI approach increases the power and
      efficiency of screening and validation of antimycotics both under in vitro and in
      vivo conditions, thereby refining pre-clinical therapy studies.

PMID- 29572044
TI  - Identification of genome regions determining semen quality in Holstein-Friesian
      bulls using information theory.
AB  - Use of information theory can be an alternative statistical approach to detect
      genome regions and candidate genes that are associated with livestock traits. The
      aim of this study was to verify the validity of the SNPs effects on some semen
      quality variables of bulls using entropy analysis. Records from 288 Holstein
      Friesian bulls from one AI station were included. The following semen quality
      variables were analyzed: CASA kinematic variables of sperm (total motility,
      average path velocity, straight line velocity, curvilinear velocity, amplitude of
      lateral head displacement, beat cross frequency, straightness, linearity), sperm
      membrane integrity (plazmolema, mitochondrial function), sperm ATP content.
      Molecular data included 48,192 SNPs. After filtering (call rate = 0.95 and MAF =
      0.05), 34,794 SNPs were included in the entropy analysis. The entropy and
      conditional entropy were estimated for each SNP. Conditional entropy quantifies
      the remaining uncertainty about values of the variable with the knowledge of SNP.
      The most informative SNPs for each variable were determined. The computations
      were performed using the R statistical package. A majority of the loci had
      relatively small contributions. The most informative SNPs for all variables were
      mainly located on chromosomes: 3, 4, 5 and 16. The results from the study
      indicate that important genome regions and candidate genes that determine semen
      quality variables in bulls are located on a number of chromosomes. Some detected
      clusters of SNPs were located in RNA (U6 and 5S_rRNA) for all the variables for
      which analysis occurred. Associations between PARK2 as well GALNT13 genes and
      some semen characteristics were also detected.

PMID- 29572045
TI  - An update on semen collection, preservation and artificial insemination in the
      dromedary camel (Camelus dromedarius).
AB  - Artificial insemination (AI) in domestic animals is an important tool to maximise
      the use of genetically superior males and thereby insure rapid genetic progress.
      However, the application of AI in camelids has been hindered by the difficulties
      involved in collecting, as well as handling the semen due to the viscous nature
      of the seminal plasma. This review describes the challenges of semen collection
      and discusses the role of seminal plasma as well as the reasons for the viscosity
      and how to liquefy it so that ejaculates can be more accurately evaluated. It
      also reports on the use of various extenders used for liquid storage of fresh and
      chilled semen and how pregnancy rates are affected by numbers of spermatozoa
      inseminated, site of insemination and timing of insemination in relation to GnRH
      injection given to induce ovulation. In addition, this paper reviews the latest
      research in cryopreservation of camel semen and addresses the various problems
      involved and possible improvements that can be made so that pregnancy rates can
      be increased with frozen semen.

PMID- 29572046
TI  - Neurotoxicity screening of new psychoactive substances (NPS): Effects on neuronal
      activity in rat cortical cultures using microelectrode arrays (MEA).
AB  - While the prevalence and the use of new psychoactive substances (NPS) is steadily
      increasing, data on pharmacological, toxicological and clinical effects is
      limited. Considering the large number of NPS available, there is a clear need for
      efficient in vitro screening techniques that capture multiple mechanisms of
      action. Neuronal cultures grown on multi-well microelectrode arrays (mwMEAs) have
      previously proven suitable for neurotoxicity screening of chemicals,
      pharmaceuticals and (illicit) drugs. We therefore used rat primary cortical
      cultures grown on mwMEA plates to investigate the effects of eight NPS (PMMA,
      alpha-PVP, methylone, MDPV, 2C-B, 25B-NBOMe, BZP and TFMPP) and two 'classic'
      illicit drugs (cocaine, methamphetamine) on spontaneous neuronal activity. All
      tested drugs rapidly and concentration-dependently decreased the weighted mean
      firing rate (wMFR) and the weighted mean burst rate (wMBR) during a 30 min acute
      exposure. Of the 'classic' drugs, cocaine most potently inhibited the wMFR (IC50
      9.8 MUM), whereas methamphetamine and the structurally-related NPS PMMA were much
      less potent (IC50 100 MUM and IC50 112 MUM, respectively). Of the cathinones,
      MDPV and alpha-PVP showed comparable IC50 values (29 MUM and 21 MUM,
      respectively), although methylone was 10-fold less potent (IC50 235 MUM).
      Comparable 10-fold differences in potency were also observed between the
      hallucinogenic phenethylamines 2C-B (IC50 27 MUM) and 25B-NBOMe (IC50 2.4 MUM),
      and between the piperazine derivatives BZP (IC50 161 MUM) and TFMPP (IC50 19
      MUM). All drugs also inhibited the wMBR and concentration-response curves for
      wMBR and wMFR were comparable. For most drugs, IC50 values are close to the
      estimated human brain concentrations following recreational doses of these drugs,
      highlighting the importance of this efficient in vitro screening approach for
      classification and prioritization of emerging NPS. Moreover, the wide range of
      IC50 values observed for these and previously tested drugs of abuse, both within
      and between different classes of NPS, indicates that additional investigation of
      structure-activity relationships could aid future risk assessment of emerging
      NPS.

PMID- 29572047
TI  - Contamination trends and factors affecting the transfer of hexabromocyclododecane
      diastereomers, tetrabromobisphenol A, and 2,4,6-tribromophenol to breast milk in
      Japan.
AB  - This study investigated contamination trends and factors affecting the levels of
      brominated flame retardants (BFRs), including hexabromocyclododecane (HBCD)
      diastereomers, tetrabromobisphenol A (TBBP-A), and 2,4,6-tribromophenol (2,4,6
      TBP), in breast milk in Japan. Breast milk samples (n = 64) were collected from
      mothers living in six prefectures in Japan. The mean concentrations were 2.2,
      0.19, 0.29, 3.0, and 0.59 ng/g lipid weight for alpha-HBCD, beta-HBCD, gamma
      HBCD, TBBP-A, and 2,4,6-TBP, respectively. Based on the previous studies, the
      levels of SigmaHBCD in Japanese women's milk appear to be increasing, and the
      levels of TBBP-A are higher than those in other Asian countries. Although
      SigmaHBCD were not correlated to phenolic BFRs, the concentration of beta-HBCD
      was significantly correlated to the concentrations of TBBP-A (r = 0.440, p <
      0.01) and 2,4,6-TBP (r = 0.320, p < 0.01). The concentration of gamma-HBCD
      increased significantly with maternal age (r = 0.378, p < 0.01), but the
      concentrations of the other analytes were not dependent on age. The concentration
      of alpha-HBCD was higher in primiparae than in multiparae (p < 0.05), while TBBP
      A was higher in multiparae. No significant correlation was found between the
      phenolic BFR levels in milk and mothers' age, working place, and drinking/smoking
      habits. These results suggest that exposure to alpha- and gamma-HBCD
      diastereomers could be affected by maternal age and parity, respectively, because
      of their different kinetics and sources. Therefore, these factors should be
      considered when conducting infant risk assessments.

PMID- 29572048
TI  - Quality and Efficiency Improvement Tools for Every Radiologist.
AB  - In an era of value-based medicine, data-driven quality improvement is more
      important than ever to ensure safe and efficient imaging services. Familiarity
      with high-value tools enables all radiologists to successfully engage in quality
      and efficiency improvement. In this article, we review the model for improvement,
      strategies for measurement, and common practical tools with real-life examples
      that include Run chart, Control chart (Shewhart chart), Fishbone (Cause-and
      Effect or Ishikawa) diagram, Pareto chart, 5 Whys, and Root Cause Analysis.

PMID- 29572049
TI  - A Radiomics Signature in Preoperative Predicting Degree of Tumor Differentiation
      in Patients with Non-small Cell Lung Cancer.
AB  - RATIONALE AND OBJECTIVES: Poorly differentiated non-small cell lung cancer
      (NSCLC) indicated a poor prognosis and well-differentiated NSCLC indicates a
      noninvasive nature and good prognosis. The purpose of this study was to build and
      validate a radiomics signature to predict the degree of tumor differentiation
      (DTD) for patients with NSCLC. MATERIALS AND METHODS: A total of 487 patients
      with pathologically diagnosed NSCLC were retrospectively included in our study.
      Five hundred ninety-one radiomics features were extracted from each tumor from
      the contrast-enhanced computed tomography images. A minimum redundancy maximum
      relevance algorithm and a logistic regression model were used for dimension
      reduction, feature selection, and radiomics signature building. The performance
      of the radiomics signature was assessed using receiver operating characteristic
      analysis, and the area under the receiver operating characteristic curve (AUC),
      sensitivity, specificity, and accuracy were calculated to quantify the
      association between a signature and DTD. An independent validation set contained
      184 consecutive patients with NSCLC. RESULTS: A nine-radiomics-feature-based
      signature was built and it could differentiate low and high DTDs in the training
      set (AUC = 0.763, sensitivity = 0.750, specificity = 0.665, and accuracy =
      0.687), and the radiomics signature had good discrimination performance in the
      validation set (AUC = 0.782, sensitivity = 0.608, specificity = 0.752, and
      accuracy = 0.712). CONCLUSIONS: A radiomics signature based on contrast-enhanced
      computed tomography imaging is a potentially useful imaging biomarker for
      differentiating low from high DTD in patients with NSCLC.

PMID- 29572050
TI  - Variability of CT Airways Measurements in COPD Patients Between Morning and
      Afternoon: Comparisons to Variability of Spirometric Measurements.
AB  - RATIONALE AND OBJECTIVES: Computed tomography (CT) airways measurements can be
      used as surrogates to spirometric measurements for assessing bronchodilation in a
      particular patient with chronic obstructive pulmonary disease. Although
      spirometric measurements show variations within the opening hours of a hospital
      department, we aimed to compare the variability of CT airways measurements
      between morning and afternoon in patients with chronic obstructive pulmonary
      disease to that of spirometric measurements. MATERIALS AND METHODS: Twenty
      patients had pulmonary function tests and CT around 8 am and 4 pm. Luminal area
      (LA) and wall thickness (WT) of third and fourth generation airways were measured
      twice by three readers. The percentage of airway area occupied by the wall (WA%)
      and the square root of wall area at an internal perimeter of 10 mm (?WAPi10) were
      calculated. The effects of examination time, reader, and measurement session on
      CT airways measurements were assessed, and the variability of these measurements
      was compared to that of spirometric measurements. RESULTS: Variability of LA3rd
      and LA4th was greater than that of spirometric measurements (P values ranging
      from <.001 to .033). There was no examination time effect on ?WAPi10, WT3rd,
      LA4th, or WA%4th (P values ranging from .102 to .712). There was a reader effect
      on all CT airways measurements (P values ranging from <.001 to .028), except in
      WT3rd (P> .999). There was no effect of measurement session on any CT airway
      measurement (P values ranging from .535 to >.999). CONCLUSION: As the variability
      of LA3rd and LA4th is greater than that of spirometric measurements, clinical
      studies should include cohorts with larger numbers of patients when considering
      LA than when considering spirometric measurements as end points.

PMID- 29572051
TI  - Botulinum toxin type A and gabapentin attenuate postoperative pain and NK1
      receptor internalization in rats.
AB  - Treatment of postoperative pain remains a challenge in clinic. Botulinum toxin
      type A (BoNT/A) and gabapentin regulate the release of neurotransmitters from
      primary afferent neurons, but their effects of on postoperative pain are not
      clear. In the current study, using pain behavioral tests, Western blot analysis,
      and immunocytochemistry, we examined whether BoNT/A, alone or in combination with
      intrathecal gabapentin, inhibited pain hypersensitivity and attenuated the
      increase in neurokinin 1 (NK1) receptor internalization in dorsal horn neurons
      after plantar incision. Our data showed that pretreatment of rats with an
      intraplantar (2 U) 24 h before plantar incision or intrathecal (0.5 U) injection
      of BoNT/A 48 h before plantar incision induced a prolonged (3-5 days) decrease in
      pain scores and mechanical hypersensitivity, as compared to those observed with
      saline pretreatment. Both intraplantar and intrathecal BoNT/A pretreatment
      reduced synaptosomal-associated protein 25 levels in the ipsilateral lumbar
      dorsal root ganglia and spinal cord dorsal horn, and attenuated the increase in
      NK1 receptor internalization in dorsal horn neurons. Intrathecal administration
      of a sub-effective dose of gabapentin (50 MUg) with BoNT/A (0.5 U) induced
      greater inhibition of pain hypersensitivity and NK1 receptor internalization than
      BoNT/A alone. These findings suggest that pretreatment with BoNT/A, alone or in
      combination with intrathecal gabapentin, may present a promising multimodal
      analgesia regimen for postoperative pain treatment.

PMID- 29572052
TI  - Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via
      activating AXL/PI3K/Akt/NF-kappaB signaling pathway.
AB  - Malignant glioma is an aggressive type of brain tumor with poor prognosis and
      mostly incurable. Although cisplatin is used for adjuvant chemotherapy against
      glioma, intrinsic and acquired resistance restricts the application of cisplatin.
      Long noncoding RNA (lncRNA) DANCR is reported to regulate the differentiation and
      progression of several cancers. However, whether DANCR participates in cisplatin
      resistance of glioma is still unknown. In this study, we found that DANCR
      expression was negatively correlated with cisplatin sensitivity in glioma cells.
      Gain-of and loss-of function assays revealed that DNACR attenuated cisplatin
      induced cell proliferation inhibition in vitro and xenograft growth suppression
      in vivo. Furthermore, DNACR also attenuated cisplatin-induced cell apoptosis in
      vitro and in vivo. Mechanistically, we found that DANCR upregulated AXL via
      competitively binding miR-33a-5p, miR-33b-5p, miR-1-3p, miR-206, and miR-613.
      Through upregulating AXL, DANCR activated PI3K/Akt/NF-kappaB signaling pathway in
      glioma cells. Inhibiting AXL/PI3K/Akt/NF-kappaB signaling pathway reversed the
      effects of DANCR on cisplatin resistance. In conclusion, we identified a
      cisplatin-resistance associated lncRNA DANCR. DANCR promotes cisplatin resistance
      via activating AXL/PI3K/Akt/NF-kappaB signaling pathway in glioma. Our data
      suggested that DANCR would be a potential biomarker for predicting cisplatin
      sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.

PMID- 29572053
TI  - Exposure to far-infrared rays attenuates methamphetamine-induced recognition
      memory impairment via modulation of the muscarinic M1 receptor, Nrf2, and PKC.
AB  - We demonstrated that activation of protein kinase Cdelta (PKCdelta) and
      inactivation of the glutathione peroxidase-1 (GPx-1)-dependent systems are
      critical for methamphetamine (MA)-induced recognition memory impairment. We also
      demonstrated that exposure to far-infrared rays (FIR) causes induction of the
      glutathione (GSH)-dependent system, including induction of the GPx-1 gene. Here,
      we investigated whether exposure to FIR rays affects MA-induced recognition
      memory impairment and whether it modulates PKC, cholinergic receptors, and the
      GSH-dependent system. Because the PKC activator bryostatin-1 mainly induces
      PKCalpha, PKCepsilon, and PKCdelta, we assessed expression of these proteins
      after MA treatment. MA treatment selectively increased PKCdelta expression and
      its phosphorylation. Exposure to FIR rays significantly attenuated MA-induced
      increases in PKCdelta phosphorylation. Importantly, bryostatin-1 potentiated MA
      induced phosphorylation of PKCdelta. MA treatment significantly decreased M1, M3,
      and M4 muscarinic acetylcholine receptors (mAChRs) and beta2 nicotinic
      acetylcholine receptor expression. Of these, the decrease was most pronounced in
      M1 mAChR. Exposure to FIR significantly attenuated MA-induced decreases in the M1
      mAChR and phospho-ERK1/2, while it facilitated Nrf2-dependent GSH induction.
      Dicyclomine, an M1 mAChR antagonist, and l-buthionine-(S, R)-sulfoximine (BSO),
      an inhibitor of GSH synthesis, counteracted against the protective potentials
      mediated by FIR. More importantly, the memory-enhancing potential of FIR rays was
      significantly counteracted by bryostatin-1, dicyclomine, and BSO. Our results
      suggest that exposure to FIR rays attenuates MA-induced impairment in recognition
      memory via up-regulation of M1 mAChR, Nrf2-dependent GSH induction, and ERK1/2
      phosphorylation by inhibiting PKCdelta phosphorylation by bryostatin-1.

PMID- 29572054
TI  - Nephron-sparing Surgery for Syndromic Wilms' Tumor: Robotic Approach.
AB  - The current standard treatment for stage I Wilms' tumor is open radical
      nephrectomy. Patients with WAGR syndrome and Wilms' tumor have risk of
      contralateral tumor and are a group of patients benefitted by nephron-sparing
      surgery (NSS). Whereas laparoscopic NSS has been attempted in such patients, due
      to the inherent technical limitations it has failed to gain popularity. Robotic
      approach for NSS overcomes limitations of movement and dexterity occurring with
      laparoscopic approach. However, the existing literature in robotic NSS in
      children is very limited. We present the first report of robotic approach for NSS
      in a child with WAGR syndrome.

PMID- 29572055
TI  - Prospective Evaluation of Predictors of Testis Atrophy After Surgery for Testis
      Torsion in Children.
AB  - OBJECTIVE: To prospectively correlate pain duration, red scrotal skin, ultrasound
      appearance of testis, and intraoperative testis color to future testis atrophy
      after acute testicular torsion. METHODS: Patients 2 months-18 years old with
      unilateral acute scrotum were consecutively enrolled in a National Institutes of
      Health transcutaneous near-infrared spectroscopy study, with a subgroup analysis
      of the true torsion group. Presence or absence of red scrotal skin, pain
      duration, testicular heterogeneity on preoperative ultrasound, and intraoperative
      testis color based on a novel visual chart 5 minutes after detorsion were
      recorded. All testes underwent orchiopexy regardless of appearance. Percent
      volume difference between normal and torsed testicles on follow-up ultrasound was
      compared between patients with and without risk factors. RESULTS: Thirty of 56
      patients who had surgical detorsion underwent scrotal ultrasound at a mean of 117
      days after surgery. A color of black or hemorrhagic 5 minutes after detorsion,
      pain duration >12 hours, and heterogeneous parenchyma on preoperative ultrasound
      were associated with significant testis volume loss in follow-up compared with
      normal testis. All patients with a black or hemorrhagic testis had >80% volume
      loss. Erythematous scrotal skin was not significantly associated with smaller
      affected testis volume in follow-up. CONCLUSION: Based on the high atrophy rate,
      orchiectomy can be considered for testes that are black or hemorrhagic 5 minutes
      after detorsion. Pain duration >12 hours and parenchymal heterogeneity on
      preoperative ultrasound were also associated with testis atrophy. Red scrotal
      skin was not a reliable predictor of atrophy and should not delay exploration.

PMID- 29572056
TI  - The Impact of the Choosing Wisely Campaign in Urology.
AB  - OBJECTIVE: To determine if 3 of the Canadian Urological Association's Choosing
      Wisely recommendations (released in 2013-2014) related to urologic care altered
      physician and patient behavior. METHODS: Administrative data from Ontario, Canada
      between 2008 and 2017 was used. We identified 3 cohorts: First, we determined how
      many men >66 years of age had a serum testosterone level before starting
      testosterone therapy. Second, we determined how many boys undergoing an
      orchiopexy underwent abdominal imaging before their surgery. Third, we determined
      how many men with low risk prostate cancer underwent a Bone Scan after diagnosis.
      Piece-wise linear regression was used to evaluate for a significant change after
      Choosing Wisely. RESULTS: We identified 13,113 men who had their initial
      prescription for testosterone filled. Serum testosterone measurement increased
      over time, from approximately 43% to 68%. There were 9319 boys who underwent an
      orchiopexy. The use of pre-orchiopexy ultrasound was generally stable
      (approximately 55%). We identified 27,174 men with low risk prostate cancer. The
      use of bone scans after diagnosis decreased over time from approximately 24% to
      20%. In all 3 of these groups, there was no significant change after Choosing
      Wisely (P = .74, P = .70, P = .72 respectively). CONCLUSION: In Ontario, there
      was no evidence of a significant change in 3 practice patterns that were featured
      in Choosing Wisely Urology recommendations. Further thought may be needed on how
      to translate these and future recommendations into behavior change.

PMID- 29572057
TI  - Reply by the Authors.

PMID- 29572058
TI  - Laparoscopic-assisted Versus Open Appendicovesicostomy Procedure in Patients With
      Prior Abdominal Surgeries: A Comparative Study.
AB  - OBJECTIVE: To determine the differences in perioperative and postoperative
      outcomes between laparoscopic-assisted approach and open approach for
      appendicovesicostomy operations without concomitant procedures, among patients
      with prior abdominal surgeries. METHODS: A Research Ethics Board-approved
      retrospective cohort study was performed to review all laparoscopic-assisted vs
      open appendicovesicostomy procedures performed without concomitant procedure in
      patient with prior abdominal surgeries from January 2000 to January 2015 in our
      institution. We evaluated the baseline characteristics, perioperative and
      postoperative outcomes such as operative time, hospital stay, estimated blood
      loss, complications, and long-term continence. Fisher exact test and Mann-Whitney
      U test were performed to compare the 2 surgical groups. RESULTS: A total of 23
      patients (11 open and 12 laparoscopic-assisted) were included. Baseline
      characteristics between the groups were not significantly different. Procedure
      time was comparable (Open median 289 [interquartile range {IQR} 230-335] vs
      laparoscopic-assisted median 231 [IQR 170.5-284]; P = .090). Significantly lower
      estimated blood loss and shorter hospital stay were noted among the laparoscopic
      assisted group (median 100 [IQR 75-200] vs 50 [IQR 25-100], P = .048; median 6
      [IQR 5-8] vs 3.5 [IQR 3-5], P = .029; respectively). Complication rates of
      Clavien-Dindo class 3 in both groups were not significantly different (6 of 11 vs
      8 of 12, P = .68). Stomal stenosis and continence rates were also not
      significantly different between the groups (36.4% vs 25%, P = .667 and 63.3% vs
      83.3%, P = .371). CONCLUSION: Laparoscopic-assisted approach to create
      catheterizable stomas among patients with prior abdominal surgeries seems to be
      comparable to the open technique with the advantage of lower blood loss and
      shorter hospital stay.

PMID- 29572059
TI  - Re: Vetterlein et al.: State-by-state Variation in Prostate-specific Antigen
      Screening Trends Following the 2011 United States Preventive Services Task Force
      Panel Update (Urology 2018;112:56-65).

PMID- 29572060
TI  - A Survey of the Current Practice Patterns of Contralateral Testis Fixation in
      Unilateral Testicular Conditions.
AB  - OBJECTIVE: To query the current contralateral testis fixation (CTF) practice
      patterns among pediatric urologists in different clinical situations that could
      result in monorchism. METHODS: An online survey was sent to members of the
      Urology Section of the American Academy of Pediatrics. The survey included
      questions addressing CTF practice patterns in 14 clinical scenarios. Responses
      were anonymously submitted, blindly reviewed, and analyzed. RESULTS: Among 53
      respondents, 62.3% had academic appointments and 73.6% had an exclusive pediatric
      urology practice. All participants agreed on CTF necessity in testicular torsion
      beyond the neonatal period. CTF was advocated by 84.9% in prenatal torsion, 96.2%
      in postnatal torsion, and 94.3% in delayed torsion presentation. Emergent
      intervention was favored by 64.4% in prenatal and 98% in postnatal torsion. Only
      1 participant (1.9%) preferred CTF with a unilateral testicular tumor and 5
      (9.4%) in trauma substantiating an orchiectomy. There was less consensus on CTF
      in torsed undescended testis (79.3% in prepubertal and 81.13% in postpubertal),
      testicular nubbin in a child (40.4%), palpable atrophic undescended testis
      (13.2%), and unilateral bell-clapper anomaly (47.2%). In situations other than
      torsion, lack of strong evidence was the commonest reason not to perform CTF.
      CONCLUSION: The majority of responding pediatric urologists currently performs
      CTF in neonatal torsion. Although there is a general consensus on CTF in
      testicular torsion outside the neonatal period, CTF remains controversial in
      other clinical situations, warranting further research. The decision for CTF
      should involve patients, parents, and treating physicians.

PMID- 29572061
TI  - Voxel-based lesion analysis of brain regions underlying reading and writing.
AB  - The neural basis of reading and writing has been a source of inquiry as well as
      controversy in the neuroscience literature. Reading has been associated with both
      left posterior ventral temporal zones (termed the "visual word form area") as
      well as more dorsal zones, primarily in left parietal cortex. Writing has also
      been associated with left parietal cortex, as well as left sensorimotor cortex
      and prefrontal regions. Typically, the neural basis of reading and writing are
      examined in separate studies and/or rely on single case studies exhibiting
      specific deficits. Functional neuroimaging studies of reading and writing
      typically identify a large number of activated regions but do not necessarily
      identify the core, critical hubs. Last, due to constraints on the functional
      imaging environment, many previous studies have been limited to measuring the
      brain activity associated with single-word reading and writing, rather than
      sentence-level processing. In the current study, the brain correlates of reading
      and writing at both the single- and sentence-level were studied in a large sample
      of 111 individuals with a history of chronic stroke using voxel-based lesion
      symptom mapping (VLSM). VLSM provides a whole-brain, voxel-by-voxel statistical
      analysis of the role of distinct regions in a particular behavior by comparing
      performance of individuals with and without a lesion at every voxel. Rather than
      comparing individual cases or small groups with particular behavioral
      dissociations in reading and writing, VLSM allowed us to analyze data from a
      large, well-characterized sample of stroke patients exhibiting a wide range of
      reading and writing impairments. The VLSM analyses revealed that reading was
      associated with a critical left inferior temporo-occipital focus, while writing
      was primarily associated with the left supramarginal gyrus. Separate VLSM
      analyses of single-word versus sentence-level reading showed that sentence-level
      reading was uniquely associated with anterior to mid-portions of the middle and
      superior temporal gyri. Both single-word and sentence-level writing overlapped to
      a great extent in the left supramarginal gyrus, but sentence-level writing was
      associated with additional underlying white matter pathways such as the internal
      capsule. These findings suggest that critical aspects of reading and writing
      processes diverge, with reading relying critically on the ventral visual
      recognition stream and writing relying on a dorsal visuo-spatial-motor stream.

PMID- 29572062
TI  - Better imagined: Neural correlates of the episodic simulation boost to
      prospective memory performance.
AB  - Episodic simulation is an adaptive process that can support goal-directed
      activity and planning success. We investigated the neural architecture associated
      with the episodic simulation improvement to the likelihood of carrying out future
      actions by isolating the brain regions associated with this facilitation in a
      prospective memory paradigm. Participants performed a lexical decision task by
      making word/non-word judgments, with rarely occurring prospective memory target
      words requiring a pre-specified manual response. Prior to scanning, participants
      were given exposure to two lists of prospective memory targets: animals and
      tools. In a fully counterbalanced design, participants generated a rhyme to one
      target list and imagined their subsequent encounter (episodic simulation) with
      target words on the other list. Replicating prior behavioral work, episodic
      simulation improved subsequent prospective memory performance. Brain activation
      was assessed in a multivariate partial least squares analysis. Relative to
      lexical decision blocks with no prospective memory demand, sustained prospective
      memory replicated prior observations of frontal polar activation. Critically,
      maintaining the intention to respond to simulated targets, over and above rhyme
      targets, engaged middle frontal and angular gyri, and medial parietal and
      prefrontal cortices. Transient activity associated with prospective memory target
      hits revealed activation for simulated targets in medial prefrontal cortex,
      posterior cingulate, lateral temporal lobe and inferior parietal lobule. In
      contrast, rhyme target hits engaged more left lateralized dorsolateral prefrontal
      cortex and anterior insula. Episodic simulation, thus effectively shifts
      executive control strategy and boosts task performance. These results are
      consistent with a growing body of evidence implicating executive control and
      default network region interactions in adaptive, goal-directed behavior.

PMID- 29572063
TI  - Agnosia for bird calls.
AB  - The cognitive organisation of nonverbal auditory knowledge remains poorly
      defined. Deficits of environmental sound as well as word and visual object
      knowledge are well-recognised in semantic dementia. However, it is unclear how
      auditory cognition breaks down in this disorder and how this relates to deficits
      in other knowledge modalities. We had the opportunity to study a patient with a
      typical syndrome of semantic dementia who had extensive premorbid knowledge of
      birds, allowing us to assess the impact of the disease on the processing of
      auditory in relation to visual and verbal attributes of this specific knowledge
      category. We designed a novel neuropsychological test to probe knowledge of
      particular avian characteristics (size, behaviour [migratory or nonmigratory],
      habitat [whether or not primarily water-dwelling]) in the nonverbal auditory,
      visual and verbal modalities, based on a uniform two-alternative-forced-choice
      procedure. The patient's performance was compared to healthy older individuals of
      similar birding experience. We further compared his performance on this test of
      bird knowledge with his knowledge of familiar human voices and faces. Relative to
      healthy birder controls, the patient showed marked deficits of bird call and bird
      name knowledge but relatively preserved knowledge of avian visual attributes and
      retained knowledge of human voices and faces. In both the auditory and visual
      modalities, his knowledge of the avian characteristics of size and behaviour was
      intact whereas his knowledge of the associated characteristic of habitat was
      deficient. This case provides further evidence that nonverbal auditory knowledge
      has a fractionated organisation that can be differentially targeted in semantic
      dementia.

PMID- 29572064
TI  - The Role of AMPK in Neuromuscular Biology and Disease.
AB  - AMP-activated protein kinase (AMPK) is a primary regulator of cellular
      metabolism. Recent studies have revealed that AMPK also mediates the maintenance
      and plasticity of alpha-motoneurons, the neuromuscular junction, and skeletal
      muscle. Furthermore, AMPK stimulation by either genetic, pharmacological, or
      physiological approaches elicits beneficial phenotypic remodeling in
      neuromuscular disorders (NMDs). Here, we review the role of AMPK as a governor of
      neuromuscular biology, and present evidence for AMPK as an effective molecular
      target for therapeutic pursuit in the context of the most prevalent NMDs,
      including Duchenne muscular dystrophy, spinal muscular atrophy, and myotonic
      dystrophy type 1. This information may be useful for engineering AMPK-targeted
      pharmacological- or lifestyle-based strategies to treat disorders of the
      neuromuscular system.

PMID- 29572065
TI  - Pericentromeric regions of homozygosity on the X chromosome: Another likely
      benign population variant.
AB  - PURPOSE: While chromosomal regions of homozygosity (ROH) may implicate genes in
      known recessive disorders, their correlation to disease pathogenicity remains
      unclear. ROH around the centromere of the X chromosome (pericentromeric, pROH) is
      regarded as benign, although this has not been empirically demonstrated. METHODS:
      We examined microarray results from 122 female individuals harboring ROH
      bordering the X centromere. RESULTS: Consecutive ROH was most frequently observed
      for regions Xp11.23 to Xp11.21 and Xq11.1 to Xq12, with an average total size of
      16.5 Mb. X chromosome pROH was unlikely related to phenotype in 41% (50/122) of
      cases due to other explanations: likely pathogenic deletion/duplication (17%,
      21/122), apparently unaffected female (7%, 8/122), other clinical explanation
      (7%, 9/122), or consanguinity (10%, 12/122). Of the remaining cases with pROH as
      the only finding, four genes were associated with recessive disorders that
      overlapped one or more clinical features reported in our probands (KDM5C, FGD1,
      ZC4H2, and LAS1L). X chromosome pROH observed in our cohort overlapped with
      previously reported regions. CONCLUSIONS: pROH on the X chromosome are commonly
      observed in both affected individuals with alternate causes of disease as well as
      in unaffected individuals, suggesting that X chromosome pROH has no clinically
      significant effect on phenotype.

PMID- 29572066
TI  - [Usefulness of local health reports to link the incidence rate of diarrhea with
      the quality of drinking water].
AB  - In this study, we analyzed the reports of the health care center located in
      Vaqueros (Salta, Argentina) over an 8-month period. Moreover, we determined the
      concentration of Escherichia coli and Giardia spp. cysts in samples from four
      different drinking water sources. A statistical relationship between water
      quality and cases of diarrhea could not be found. However, using an odds ratio
      calculation, it was possible to determine that one of the studied drinking water
      systems acts as a protection factor in cases of diarrhea. The present work
      provides useful information for planning preventive measures by the local health
      system.

PMID- 29572067
TI  - Independent roles of CGRP in cardioprotection and hemodynamic regulation in
      ischemic postconditioning.
AB  - Calcitonin gene-related peptide (CGRP) may participate in ischemic post
      conditioning (IPost) attenuating myocardial ischemia/reperfusion injury. However,
      the molecular mechanism underlying the effect of CGRP is still elusive. In this
      study, we evaluated the difference in hemodynamics, infarct size and CGRP in
      myocardium and serum of rats after acute myocardial ischemia/reperfusion with and
      without IPost. A specific antagonist of CGRP receptor, CGRP8-37 was employed to
      testify the role of endogenous CGRP in IPost. The underlying mechanism was
      investigated by evaluation of the effect of CGRP on the changes in cytosolic
      reactive oxygen species, mitochondrial membrane potential and myocyte apoptosis
      induced by hypoxia/reoxygenation in cultured cardiomyocytes of neonatal rats. The
      results showed that IPost significantly upgraded CGRP in myocardium and serum
      with reduced infarct size, independent of the reductions in blood pressures
      observed in this study. The effects were significantly reversed by CGRP8-37,
      indicating an involvement of intrinsic CGRP. It was further demonstrated that
      CGRP effectively reversed the hypoxia/reoxygenation-induced reduction of
      mitochondrial membrane potential and attenuated the increases of cytosolic
      reactive oxygen species and cardiomyocyte apoptosis. The findings may demonstrate
      that CGRP mediates the cardioprotective and vasoactive effects of IPost.
      Homeostasis of cytosolic reactive oxygen species and mitochondrial membrane
      potential may be underlying the cardioprotective effect of CGRP.

PMID- 29572069
TI  - Two-detector number and brightness analysis reveals spatio-temporal
      oligomerization of proteins in living cells.
AB  - Number and brightness analysis (N&B) is a useful tool for the simultaneous
      visualization of protein oligomers and their localization, with single-molecule
      sensitivity. N&B determines particle brightness (fluorescence intensity per
      particle) and maps the spatial distribution of fluorescently labeled proteins by
      performing statistical analyses of the image series obtained using laser scanning
      microscopy. The brightness map reveals presence of the oligomers of the targeted
      protein and their distribution in living cells. However, even when corrections
      are applied, conventional N&B is affected by afterpulsing, shot noise, thermal
      noise, dead time, and overestimation of particle brightness when the
      concentration of the fluorescent particles changes during measurement. The
      drawbacks of conventional N&B can be circumvented by using two detectors, a novel
      approach that we henceforth call two-detector number and brightness analysis (TD
      N&B), and introducing a linear regression of fluorescence intensity. This
      statistically eliminates the effect of noise from the detectors, and ensures that
      the correct particle brightness is obtained. Our method was theoretically
      assessed by numerical simulations and experimentally validated using a dilution
      series of purified enhanced green fluorescent protein (EGFP), EGFP tandem
      oligomers in cell lysate, and EGFP tandem oligomers in living cells. Furthermore,
      this method was used to characterize the complex process of ligand-induced
      glucocorticoid receptor dimerization and their translocation to the cell nucleus
      in live cells. Our method can be applied to other oligomer-forming proteins in
      cell signaling, or to aggregations of proteins such as those that cause
      neurodegenerative diseases.

PMID- 29572068
TI  - Polygodial analog induces apoptosis in LNCaP prostate cancer cells.
AB  - Prostate cancer (PCa) is the second leading cause of death in American men. The
      chemotherapeutic treatment strategies are generally not effective and can lead to
      side effects. Hence, there is an urgent need to identify novel chemotherapeutic
      agents. The aim of this study was to synthesize and evaluate the therapeutic
      effects of a synthetic analog of polygodial (PG), a pungent constituent
      abundantly present in mountain pepper, water pepper and dorrigo pepper, on LNCaP
      PCa cell line and its anti-cancer mechanisms in a preclinical study. We evaluated
      the anti-cancer potential of the PG analog namely DRP-27 using various assays
      such as cell viability by MTT assay, anchorage independent growth by soft agar
      assay, reactive oxygen species generation by 2',7'-dichlorofluorescein probe
      based fluorescence assay, and apoptosis by Annexin-V and TUNEL assays
      respectively. Western blot analysis was performed to identify the molecular
      mechanism of DRP-27-induced cell death. Our results showed that DRP-27
      significantly inhibited LNCaP cell proliferation in a dose-dependent manner at 48
      h treatment in vitro. In addition, DRP-27 potently inhibited anchorage
      independent growth of these cells. Flow cytometry, Annexin-V and TUNEL assays
      confirmed that DRP-27 induces apoptosis in LNCaP cells. DRP-27 also induced the
      activation of intracellular reactive oxygen species. Western blot analysis
      revealed that DRP-27 downregulated the expression of survivin, while activating
      Bax and DNA damage marker pH2AX in LNCaP cells. In conclusion, our study suggests
      that DRP-27 might be an effective anti-cancer agent for PCa.

PMID- 29572070
TI  - ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus
      Document on the safety of targeted and biological therapies: an infectious
      diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens
      [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4).
AB  - BACKGROUND: The present review is part of the ESCMID Study Group for Infections
      in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and
      biological therapies. AIMS: To review, from an Infectious Diseases perspective,
      the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and
      CCR4 and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE
      searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT:
      The risk and spectrum of infections in patients receiving CD22-targeted agents
      (i.e. inotuzumab ozogamicin) are similar to those observed with anti-CD20
      antibodies. Anti-Pneumocystis prophylaxis and monitoring for cytomegalovirus
      (CMV) infection is recommended for patients receiving CD30-targeted agents
      (brentuximab vedotin). Due to the scarcity of data, the risk posed by CD33
      targeted agents (gemtuzumab ozogamicin) cannot be assessed. Patients receiving
      CD38-targeted agents (i.e. daratumumab) face an increased risk of varicella
      zoster virus (VZV) infection. Therapy with CD40-targeted agents (lucatumumab or
      dacetuzumab) is associated with opportunistic infections similar to those
      observed in hyper-IgM syndrome, and prevention strategies (including anti
      Pneumocystis prophylaxis and pre-emptive therapy for CMV infection) are
      warranted. SLAMF-7 (CD319)-targeted agents (elotuzumab) induce lymphopenia and
      increase the risk of infection (particularly due to VZV). The impact of CCR4
      targeted agents (mogamulizumab) on infection susceptibility is difficult to
      distinguish from the effect of underlying diseases and concomitant therapies.
      However, anti-Pneumocystis and anti-herpesvirus prophylaxis and screening for
      chronic hepatitis B virus (HBV) infection are recommended. IMPLICATIONS: Specific
      management strategies should be put in place to reduce the risk and/or the
      severity of infectious complications associated to the reviewed agents.

PMID- 29572071
TI  - Long non-coding RNA HOTAIR and STAT3 synergistically regulate the cervical cancer
      cell migration and invasion.
AB  - Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic non-coding
      RNA (lncRNA) that has been reported to be highly upregulated in several types of
      cancers. However, the role of HOTAIR in human cervical cancer is still unclear.
      We therefore investigated the expression and probable function of HOTAIR in
      cervical cancer cells. The expression of HOTAIR was examined in (HeLa, CaSki, ME
      180, HT-3) and Human Cervical Epithelial Cells (HCerEpiC) by qRT-PCR.
      Transfection of si-NC, si-HOTAIR or si-STAT3 was carried out with the help of
      Lipofectamine 2000. The cell viability was assessed by CCK-8 assay. The cell
      migration and invasion was examined by wound healing and Boyden chamber assays.
      Protein expression was determined by western blotting. Our results showed that
      expression of HOTAIR was significantly upregulated in cervical cancer cells and
      inhibition of the expression of HOTAIR in HeLa cervical cancer cells resulted in
      suppression of cell proliferation, migration and invasion. Further, analysis of
      the promoter of HOTAIR, revealed that STAT3 could potentially regulate the
      activity of the HOTAIR in cervical cancer cells and inhibition of STAT3 had
      similar effects on the proliferation, migration and invasion of the cervical
      cancer cells as that of HOTAIR. Further, the suppression of STAT3 expression was
      associated with concomitant downregulation of IncRNA HOTAIR as indicated by the
      qRT-PCR. To unveil if STAT3 and HOTAIR have synergistic effects on the cell
      migration and invasion, si-STAT3 and si-HOTAIR were co-transformed into cervical
      HeLa cancer cells and it was observed that STAT3 and HOTAIR could synergistically
      inhibit the proliferation, migration and invasion of the cervical cancer cells.
      Taken together we conclude that HOTAIR and STAT3 synergistically regulate the
      proliferation, migration and invasion of cervical cancer cells.

PMID- 29572072
TI  - Effects of isopentyl ferulate on oxidative stress biomarkers and a possible
      GABAergic anxiolytic-like trait in Swiss mice.
AB  - This study aimed to evaluate the anxiolytic-like effect and the possible neuronal
      mechanism of action of isopentyl ferulate (IF). For this purpose, we used the
      marble burying test in Swiss albino mice. The biomarkers involved in oxidative
      stress were measured in the hippocampus homogenate of the test animals. In
      addition, the toxicity and antioxidant capacities were tested in Artemia salina
      and rat erythrocytes, respectively. The results suggest that, an acute
      administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal,
      i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals
      as compared to the vehicle group, which demonstrates a calming effect of this
      chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg,
      i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor,
      significantly reversed the marble burying behavioral activity in the animals
      treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content
      and lipid peroxidation levels, while an increased in the reduced glutathione
      (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase
      (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16
      mM) did not show toxicity in A. salina but exhibited a prominent antioxidant
      capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In
      conclusion, IF exhibited an anxiety-like effect in mice along with a potent
      antioxidant capacity, and we suppose it may have neuroprotective effects possibly
      via GABAergic transmission pathway.

PMID- 29572073
TI  - ROS-independent toxicity of Fe3O4 nanoparticles to yeast cells: Involvement of
      mitochondrial dysfunction.
AB  - Fe3O4 nanoparticles, one kind of magnetic nanomaterials (NMs), are widely used in
      drug delivery, biological imaging, sensors, catalysts and pollution management.
      However, its toxicity to biological systems and related toxicity mechanisms
      remain to be explored. In this study, we investigate the effect of as-synthesized
      Fe3O4 nanoparticles on growth of Saccharomyces cerevisiae, an important model
      fungus. Growth inhibition assays showed that Fe3O4 nanoparticles remarkably
      inhibited yeast growth. Interestingly, this inhibitory effect was not attributed
      to the well-known plasma membrane damage, cell wall damage and ROS accumulation.
      Further investigations revealed that the nanoparticles strongly impaired
      mitochondrial functions, resulting in abnormal mitochondrial morphology,
      decreased mitochondrial membrane potential (MMP) and attenuated ATP production.
      Most importantly, the respiratory chain complex IV, rather than other respiratory
      chain complexes and ATP synthases, was found to be the main target of the
      nanoparticles. This study uncovers a novel ROS-independent toxicity mechanism of
      Fe3O4 nanoparticles to eukaryotic cells.

PMID- 29572074
TI  - Advanced biotherapy for the treatment of sulfur mustard poisoning.
AB  - CONTEXT: Sulfur mustard (SM), a bifunctional alkylating agent, can react with a
      variety of biochemical molecules (DNA, RNA, proteins and other cell components)
      to cause a series of serious health issues or even death. Although a plethora of
      research has been done, the pathogenesis of SM poisoning has yet to be fully
      understood due to its high complexity. As a consequence, a specific antidote has
      not yet been developed and the treatment of SM poisoning remains a medical
      challenge. In recent years, various biological products and cell transplantation
      in the treatment of SM poisoning offered a significant clinical treatment
      progress. By highlighting these and other research studies, we hereby summarize
      the progress in this field in an effort to provide useful information on the
      clinical treatment of SM poisoning. OBJECTIVE: This review summarizes the major
      advances of SM poisoning therapy by means of biological products (peptide and
      protein drugs, polysaccharides drugs, nucleic acid drugs, etc.), and cell
      transplantation (e.g., bone marrow, limbal stem cells, mesenchymal stem cells),
      as well as other relevant biotherapeutic approaches. METHOD: We searched the
      database PubMed for published domestic and international articles using web based
      resources for information on histological, immunochemical, ultrastructural, and
      treatment features of SM-induced manifestations in both animal models and human
      tissues. To this end, we applied keywords containing mustard gas, chemical
      warfare, SM, eye, lung and skin. RESULTS AND CONCLUSION: Our review provides a
      comprehensive understanding of the advances of available biotherapies in SM
      poisoning, and its potential for the treatment of SM-induced injuries.
      Potentially, our review will provide new insights for future research studies in
      this field.

PMID- 29572075
TI  - Key design and analysis principles for quality of life and patient-reported
      outcomes in clinical trials.
AB  - Advances in early detection and therapy have increased the number of prostate
      cancer survivors, leading to a greater emphasis on examining patient-reported
      outcomes (PROs). PROs augment clinical outcomes, providing a more comprehensive
      assessment of the patient experience, including symptoms and quality of life,
      that may impact the overall evaluation of new therapies. The successful
      incorporation of PROs into clinical trials requires adherence to key design and
      analysis principles. We present these principles and argue that adherence to
      these principles is vital to ensure valid interpretation of clinical trial
      findings, identify meaningful differences among investigational strategies, and
      better translate clinical trial results to diverse stakeholders.

PMID- 29572076
TI  - Disruptions in resting state functional connectivity in euthymic bipolar patients
      with insomnia symptoms.
AB  - Insomnia is prevalent in bipolar disorder (BD) even during periods of euthymic
      mood. We compared resting state brain activity and cognitive function between
      euthymic BD with and without insomnia, and secondarily to healthy individuals. BD
      patients with insomnia symptoms showed a significantly lower functional
      connectivity within the task-positive network, compared to those without
      insomnia. They also showed significantly slower cognitive processing speed. These
      two features of BD with insomnia appeared relatively independent of each other.
      Preliminary findings suggest that exploration of the mechanisms of sleep
      disturbance in BD could lead to improved understanding and treatment of
      inattention in BD.

PMID- 29572077
TI  - Experience using the "Shetty test" for initial foot and ankle fracture screening
      in the Emergency Department.
AB  - OBJECTIVE: The indiscriminate practice of radiographs for foot and ankle injuries
      is not justified and numerous studies have corroborated the usefulness of
      clinical screening tests such as the Ottawa Ankle Rules. The aim of our study is
      to clinically validate the so-called Shetty Test in our area. MATERIAL AND
      METHOD: A cross-sectional observational study by applying the Shetty test to
      patients seen in the Emergency Department. RESULTS: We enrolled 100 patients with
      an average age of 39.25 (16-86). The Shetty test was positive on 14 occasions.
      Subsequent radiography revealed a fracture in 10 cases: 4 were false positives.
      The test was negative in the remaining 86 patients and radiography confirmed the
      absence of fracture (with sensitivity of 100% and specificity of 95.56%, positive
      predictive value of 71.40%, and negative predictive value of 100%). CONCLUSIONS:
      The Shetty test is a valid clinical screening tool to decide whether simple
      radiography is indicated for foot and ankle injuries. It is a simple, quick and
      reproducible test.

PMID- 29572078
TI  - Osteochondromas of the Proximal Humerus. Diagnostic and Therapeutic Management.
AB  - OBJECTIVE: 1) To recall the epidemiology and signs of osteochondromas of the
      proximal humerus (OPH); 2) determine treatment indications; 3) and make
      recommendations for surgical treatment. METHODS: Retrospective, observational and
      longitudinal study of 20 solitary and 12 multiple osteochondromas of the proximal
      humerus. We analyzed the epidemiological, clinical and imaging characteristics
      and treatment results with an average time of follow-up of the operated cases of
      45 months. RESULTS: Eleven (55%) males and 9(45%) females with an average age of
      21 years presented solitary osteochondromas. Twelve (60%) cases were operated on
      at a mean age of 23 years because they were symptomatic or, in one case,
      malignancy was suspected. Two solitary osteochondromas could have spontaneously
      regressed. Multiple osteochondromas were found in 11(92%) males and one (8%)
      female of whom 3required surgery. There were no complications or recurrences.
      Functional outcome was excellent in all patients. DISCUSSION: Osteochondromas of
      the proximal humerus are relatively common, although most publications are case
      reports or short series. CONCLUSIONS: Osteochondromas of the proximal humerus do
      not differ from those in other locations. Symptomatic cases and those in which
      malignancy is suspected would be operated, the former preferably at the end of
      growth. The surgical treatment is summarized in planning the approach, using CT
      and/or MRI, extraperiosteal en bloc resection, and eventual bone reconstruction,
      ideally with allograft.

PMID- 29572079
TI  - Recent Advances and Future Directions in Postmastectomy Breast Reconstruction.
AB  - Postmastectomy breast reconstruction (PMBR) has evolved dramatically since it was
      first described by Vincent Czerny in 1895. The increasing numbers of mastectomy
      procedures and improved patient survival have placed an increasing emphasis on
      the aesthetic and psychosocial outcomes, prompting surgeons to develop more
      sophisticated methods to reconstruct the breast mound. Significant improvements
      have been made to existing implant and autologous methods of PMBR in recent
      decades in an effort to reduce donor site morbidity and complication rates and
      improve cosmesis. The limitations of contemporary methods of PMBR have directed
      research toward more novel techniques such as autologous fat grafting and adipose
      tissue engineering. The present review discusses recent advances in the evolution
      of contemporary approaches to breast reconstruction and the future directions of
      PMBR using adipose tissue engineering strategies.

PMID- 29572080
TI  - Restarting oral anticoagulant therapy after major bleeding in atrial
      fibrillation: A systematic review and meta-analysis.
AB  - BACKGROUND: Use of oral anticoagulant (OAC) therapy in atrial fibrillation (AF)
      is associated with an inherited risk of bleeding. Benefits and risks of OAC
      restarting after a major bleeding are still uncertain. We aimed to assess
      effectiveness and safety of restarting OAC in AF patients after a major bleeding
      event. METHODS: We performed a systematic review and meta-analysis of all studies
      reporting data about AF patients that sustained a major bleeding, reporting data
      on restarting or not restarting OAC therapy. RESULTS: A total of seven studies
      were included, involving 5685 patients. No significant difference was found in
      "any stroke" occurrence between OAC restarters and non-restarters (odds ratio
      [OR]: 0.75, 95% confidence interval [CI]: 0.37-1.51), with a significant 46%
      relative risk reduction (RRR) (p < 0.00001) for "any thromboembolism" in OAC
      restarters, with consistent results when the index bleeding event was an
      intracranial or gastrointestinal bleeding. A significantly higher risk of
      recurrent major bleeding was seen (OR: 1.85, 95% CI: 1.48-2.30), but no
      difference in risk for recurrence of index event. OAC restarters had a 10.8%
      absolute risk reduction for all-cause death (OR: 0.38, 95% CI: 0.24-0.60); p <
      0.00001). Net clinical benefit (NCB) analysis demonstrated that restarting OAC
      therapy after a major bleeding was significantly associated with a clinical
      advantage (NCB: 0.11, 95% CI: 0.09-0.14; p < 0.001). CONCLUSIONS: Restarting OAC
      therapy after a major bleeding event in AF was associated with a positive
      clinical benefit when compared to non-restarting OAC, with a significant
      reduction in any thromboembolism and all-cause mortality.

PMID- 29572081
TI  - LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: Data
      from the Brisighella Heart Study cohort.
AB  - BACKGROUND: Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with
      arterial aging. The aim of our study was to evaluate the relationship between
      SUA, oxLDL and arterial stiffness in subjects with normal renal function and in
      patients with mild or moderate renal impairment. METHODS: From the database of
      the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker
      subjects without cardiovascular disease and with normal renal function (n = 205),
      subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with
      stage III CKD (n = 94). All subjects underwent a determination of the LDL
      oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV).
      RESULTS: By univariate analysis, PWV correlated with a large number of clinical,
      haemodynamic and metabolic parameters, including estimated glomerular filtration
      rate (eGFR) in subjects with normal renal function and in those with stage II or
      III CKD. Stepwise multiple regression analyses showed that in the presence of
      normal renal function or stage II CKD, the main predictors of PWV were age,
      systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while
      in the presence of stage III CKD only age, SBP and apolipoprotein B remained
      significant (p < 0.05). CONCLUSION: Both ox-LDL and SUA independently predicts
      PWV only in subjects with normal or mildly reduced renal function, but not in the
      subjects with more compromised eGFR. This study confirms the complex relationship
      of SUA with cardiovascular and metabolic disease in the patient with established
      renal disease.

PMID- 29572082
TI  - Correlation of tricuspid regurgitation and new pacemaker implantation in patients
      undergoing transcatheter aortic valve implantation.
AB  - AIMS: Conduction abnormalities (CA), in particular complete atrioventricular
      block (CAVB), requiring permanent pacemaker (PPM) implantation, are frequent
      complications after transcatheter aortic valve implantation (TAVI) in patients
      with severe aortic stenosis (AS). However, the potential mechanisms are still
      incompletely understood. The objective of this retrospective study was to
      determine further predictors of CAVB after TAVI in patients without the known
      predictors. METHODS AND RESULTS: This study included patients without prior
      CA/PPM who underwent TAVI of a balloon-expandable valve (Sapien or Sapien XT or
      Sapien 3). Of 563 patients (81.2 +/- 6.9 years, 245 men [43.5%], logistic
      EuroSCORE 22.2 +/- 14.1%, STS PROM 5.9 [3.4-8.0]) who were treated by TAVI at our
      institution between July 2008 and January 2016, 61 (10.8%) developed a permanent
      CAVB after the procedure. In a multivariable logistic regression analysis
      moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18-3.55; p =
      0.010) was identified as an independent predictor for new CAVB after TAVI.
      Moreover, patients with more pronounced TR presented with increased left and
      right ventricular overload (left ventricular (LV) end-diastolic diameter, LV end
      diastolic pressure), pulmonary pressures, NT-proBNP, and prevalence of mitral
      regurgitation >=II, whereas LV ejection fraction, TAPSE and cardiac output were
      decreased. CONCLUSIONS: PPM implantation is a frequent complication in patients
      undergoing TAVI. Increasing severity of TR seems to be a consequence of left and
      right ventricular overload caused by severe AS and is a significant predictor of
      new CAVB after TAVI. CONDENSED ABSTRACT: Conduction abnormalities (CA) requiring
      permanent pacemaker (PPM) implantation, are frequent complications after
      transcatheter aortic valve implantation (TAVI). This study included patients
      without prior CA/PPM who underwent TAVI. Of 563 patients 61 (10.8%) developed a
      permanent CAVB after the procedure. In a multivariable logistic regression
      analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18-3.55;
      p = 0.010) was identified as an independent predictor for new CAVB. Therefore, in
      patients with moderate/severe TR utmost care should be taken to avoid procedural
      factors conducive to mechanical irritation of the conduction system, resulting in
      pacemaker dependency.

PMID- 29572083
TI  - Atrial fibrillation and prediction of mortality by conventional clinical score
      systems according to the setting of care.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with high morbidity and
      mortality, also among anticoagulated patients. Our aim was to evaluate the
      predictive role for long-term mortality of a series of risk stratification scores
      associated with cardiovascular or thromboembolic outcomes (CHADS2, CHA2DS2-VASc,
      ATRIA, TIMI-AF), and bleeding complications (HAS-BLED) in an unselected
      population of patients with AF. METHODS: Single center, observational,
      prospective registry of consecutive patients with AF, undergoing
      clinical/echocardiographic evaluation in a University Hospital, as either in
      patients or out-patients. We assessed the role of each single score as predictors
      of long-term survival according to clinical setting. RESULTS: We enrolled 1051
      patients, mean age 72 +/- 12 years, who were followed for 797 +/- 298 days. All
      the tested scores showed a good performance in prediction of mortality, together
      with several clinical factors (older age, chronic heart failure, diabetes, renal
      impairment, previous transient ischemic attack, left ventricular ejection
      fraction). The values at C-statistics ranged between modest (0.608-0.684) of
      inpatients to good (0.708-0.751) in outpatients without any statistical
      difference between the scores, excepted a lower performance of HAD-BLED.
      CONCLUSIONS: Risk scores currently adopted for decision making on starting oral
      anticoagulation provide good prediction of long-term survival in unselected AF
      patients, especially in the outpatient setting.

PMID- 29572084
TI  - High intensity interval training versus moderate intensity continuous training on
      exercise capacity and quality of life in patients with heart failure with reduced
      ejection fraction: A systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of high intensity
      interval training (HIIT) versus moderate intensity continuous training (MICT) in
      heart failure patients with reduced ejection fraction (HFrEF). BACKGROUND:
      Despite the well-known positive effects of exercise in heart failure patients,
      the best mode of exercise is still under discussion. METHODS: We searched
      Pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base,
      and SciELO (from the earliest date available to October 2017) for randomized
      controlled trials that evaluated the effects of HIIT versus MICT in HFrEF
      patients. Weighted mean differences (WMD) with 95% confidence interval (CI) were
      calculated, and heterogeneity was assessed using the I2 test. RESULTS: 13 studies
      met the study criteria, including 411 patients. Compared to MICT, HIIT resulted
      in improvement in Peak VO2 WMD (1.35 mL.kg-1.min-1 95% CI: 0.03 to 2.64 N = 411).
      HIIT resulted in no difference in VE/VCO2 slope WMD (-1.21 95% CI: -3.0 to 0.58 N
      = 135), and quality of life measured by Minnesota Living with Heart Failure
      questionnaire WMD (1.19 95% CI: -5.81 to 8.19 N = 79). Sub-group analyses
      comparing studies with and without isocaloric exercise training protocol also
      showed a nonsignificant difference in peak VO2 for participants in the HIIT group
      compared with MICT group. CONCLUSIONS: HIIT improves peak VO2 and should be
      considered as a component of care of HFrEF patients. However, its superiority
      versus MICT disappears when isocaloric protocols are compared. An important
      caveat is uncertainty and variation of actual training intensities compared to
      program targets.

PMID- 29572085
TI  - Ablation strategies for the management of symptomatic Brugada syndrome: A
      systematic review.
AB  - BACKGROUND: Ablation approaches have been described for the management of
      symptomatic ventricular arrhythmias in patients with Brugada syndrome, but this
      treatment is still considered experimental. OBJECTIVE: We aimed to perform a
      systematic review of the current evidence on the use of catheter ablation in
      Brugada syndrome. METHODS: MEDLINE, Embase, and Scopus were searched for articles
      describing the use of catheter ablation for ventricular arrhythmia management in
      Brugada syndrome. RESULTS: We included 11 case series and 11 case reports
      including a total of 233 patients. Ablation strategies included epicardial
      mapping with substrate modification (n = 180; 77.3%), endocardial-only mapping
      with substrate modification (n = 17; 7.3%), ventricular fibrillation (VF)
      triggering premature ventricular complex ablation (n = 5; 2.1%), and mixed
      approaches (n = 31; 13.3%). During a 2.5- to 78-month follow-up period, the
      success rates in preventing ventricular tachycardia or VF (VT/VF) were 96.7%,
      70.6%, and 80% with epicardial, endocardial, and triggering premature ventricular
      complex ablation approaches, respectively. Among patients who underwent both
      epicardial and endocardial mapping, there was no identifiable endocardial
      substrate in 92.9% of cases. Elimination of type 1 Brugada-pattern
      electrocardiogram was attained in 98.3% and 34.8% of the epicardial and
      endocardial ablation groups, respectively. VT/VF occurred in 7 of 9 patients
      (77.8%) who had persistent or recurrent J-ST elevation and in none of the 24
      patients with complete resolution during follow-up. Pharmacologic provocation
      augmented the abnormal area. CONCLUSION: Epicardial substrate modification
      appears to be more effective than endocardial-only approach in preventing VT/VF.
      Persistent or recurrent J-ST elevation appears to represent a marker of failure
      of ablation. Ablation seems to be an acceptable strategy for patients with
      Brugada syndrome and VT/VF.

PMID- 29572086
TI  - Influence of contact force on voltage mapping: A combined magnetic resonance
      imaging and electroanatomic mapping study in patients with tetralogy of Fallot.
AB  - BACKGROUND: Voltage criteria for ventricular mapping have been obtained from
      small series of patients and prioritizing high specificity. OBJECTIVE: The
      purpose of this study was to analyse the potential influence of contact force
      (CF) on voltage mapping and to define voltage cutoff values for right ventricular
      (RV) scar using the tetralogy of Fallot as a model of transmural RV scar and
      magnetic resonance imaging (MRI) as reference. METHODS: Fourteen patients (age
      32.6 +/- 14.3 years; 5 female) with repaired tetralogy of Fallot underwent high
      resolution cardiac MRI (1.25 * 1.25 * 2.5 mm). Scar, defined as pixels with
      intensity >50% maximum, was mapped over the RV geometry and merged within the
      CARTO system to RV endocardial voltage maps acquired using a 3.5-mm ablation
      catheter with CF technology (SmartTouch, Biosense Webster). RESULTS: In total,
      2446 points were analyzed, 915 within scars and 1531 in healthy tissue according
      to MRI. CF correlated to unipolar (rho = 0.186; P <.001) and bipolar voltage in
      healthy tissue (rho = 0.245; P <.001) and in scar tissue. Receiver operating
      characteristic curve analysis excluding points with very low CF (<5g) identified
      optimal voltage cutoffs of 5.19 mV for unipolar voltage and 1.76 mV for bipolar
      voltage, yielding sensitivity/specificity of 0.89/0.85 and 0.9/0.9, respectively.
      CONCLUSION: CF is an important factor to be taken into account for voltage
      mapping. If good CF is applied, unipolar and bipolar voltage cutoffs of 5.19 mV
      and 1.76 mV are optimal for identifying RV scar on endocardial mapping with the
      SmartTouch catheter. Data on the diagnostic accuracy of different voltage cutoff
      values are provided.

PMID- 29572087
TI  - Utility of dual-source computed tomography in cardiac resynchronization therapy
      DIRECT study.
AB  - BACKGROUND: Dual-source computed tomography (CT) can evaluate left ventricular
      (LV) dyssynchrony, myocardial scar, and coronary venous anatomy in patients
      undergoing cardiac resynchronization therapy (CRT). OBJECTIVE: We aimed to
      determine whether dual-source CT predicts clinical CRT outcomes and reduces
      intraprocedural time. METHODS: In this prospective study, 54 patients scheduled
      for CRT (mean age 63 +/- 11 years; 74% men) underwent preprocedural CT to assess
      their venous anatomy as well as CT-derived dyssynchrony metrics and myocardial
      scar. Based on 1:1 randomization, the implanting physician had preimplant
      knowledge of the venous anatomy in half the patients. In blinded analyses, we
      measured time to maximal wall thickness and inward wall motion to determine (1)
      CT global and segmental dyssynchrony and (2) concordance of lead location to
      regional LV mechanical contraction. End points were 6-month CRT response measured
      using heart failure clinical composite score and 2-year major adverse cardiac
      events (MACE). RESULTS: There were 72% CRT responders and 17% with MACE. Two wall
      motion dyssynchrony indices-global wall motion and opposing anteroseptal
      inferolateral wall motion-predicted MACE (P < .01). Lead location concordant to
      regions of maximal wall thickness was associated with less MACE (P < .01). No CT
      dyssynchrony metrics predicted 6-month CRT response (P = NS for all). Myocardial
      scar (43%), posterolateral wall scar (28%), and total scar burden did not predict
      outcomes (P = NS for all). Preknowledge of coronary venous anatomy by CT did not
      reduce implant or fluoroscopy time (P = NS for both). CONCLUSION: Two CT
      dyssynchrony metrics predicted 2-year MACE, and LV lead location concordant to
      regions of maximal wall thickness was associated with less MACE. Other CT factors
      had little utility in CRT.

PMID- 29572088
TI  - Predictive Factors for Death After Snake Envenomation in Myanmar.
AB  - INTRODUCTION: Factors predictive for death from snake envenomation vary between
      studies, possibly due to variation in host genetic factors and venom composition.
      This study aimed to evaluate predictive factors for death from snake envenomation
      in Myanmar. METHODS: A prospective study was performed among adult patients with
      snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to
      August 2016. Data including clinical variables and laboratory parameters,
      management, and outcomes were evaluated. Multivariate regression analysis was
      performed to evaluate factors predictive for death at the time of presentation to
      the hospital. RESULTS: Of the 246 patients with snake envenomation recruited into
      the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake
      species responsible for a bite was identified in 74 (30%) of the patients; the
      majority of bites were from Russell's vipers (63 patients, 85%). The independent
      factors predictive for death included 1) duration from bite to arrival at the
      hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2;
      P=0.04); 2) white blood cell counts >20 *103 cells.MUL-1 (OR: 8.9, 95% CI: 2.3
      33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2
      11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death
      (11/21 deaths). CONCLUSIONS: Patients who present with these independent
      predictive factors should be recognized and provided with early appropriate
      intervention to reduce the mortality rate among adults with snake envenomation in
      Myanmar.

PMID- 29572089
TI  - Magnetic resonance imaging is often misleading when used as an adjunct to
      ultrasound in the management of placenta accreta spectrum disorders.
AB  - BACKGROUND: Magnetic resonance imaging is reported to have good sensitivity and
      specificity in the diagnosis of placenta accreta spectrum disorders, and is often
      used as an adjunct to ultrasound. But the additional utility of obtaining
      magnetic resonance imaging to assist in the clinical management of patients with
      placenta accreta spectrum disorders, above and beyond the information provided by
      ultrasound, is unknown. OBJECTIVE: We aimed to determine whether magnetic
      resonance imaging provides data that may inform clinical management by changing
      the sonographic diagnosis of placenta accreta spectrum disorders. STUDY DESIGN:
      In all, 78 patients with sonographic evidence or clinical suspicion of placenta
      accreta spectrum underwent magnetic resonance imaging of the abdomen and pelvis
      in orthogonal planes through the uterus utilizing T1- and T2-weighted imaging
      sequences at the University of Utah and the University of Colorado from 1997
      through 2017. The magnetic resonance imaging was interpreted by radiologists with
      expertise in diagnosis of placenta accreta spectrum who had knowledge of the
      sonographic interpretation and clinical risk factors for placenta accreta
      spectrum disorders. The primary outcome was a change in diagnosis from
      sonographic interpretation that could alter clinical management, which was
      defined a priori. Diagnostic accuracy was verified by surgical and
      histopathologic diagnosis at the time of delivery. RESULTS: A change in diagnosis
      that could potentially alter clinical management occurred in 28 (36%) cases.
      Magnetic resonance imaging correctly changed the diagnosis in 15 (19%), and
      correctly confirmed the diagnosis in 34 (44%), but resulted in an incorrect
      change in diagnosis in 13 (17%), and an incorrect confirmation of ultrasound
      diagnosis in 15 (21%). Magnetic resonance imaging was not more likely to change a
      diagnosis in the 24 cases of posterior and lateral placental location compared to
      anterior location (33% vs 37%, P = .84). Magnetic resonance imaging resulted in
      overdiagnosis in 23% and in underdiagnosis in 14% of all cases. When ultrasound
      suspected severe disease (percreta) in 14 cases, magnetic resonance imaging
      changed the diagnosis in only 2 cases. Lastly, the proportion of accurate
      diagnosis with magnetic resonance imaging did not improve over time (61-65%, P =
      .96 for trend) despite increasing volume and increasing numbers of changed
      diagnoses. CONCLUSION: Magnetic resonance imaging resulted in a change in
      diagnosis that could alter clinical management of placenta accreta spectrum
      disorders in more than one third of cases, but when changed, the diagnosis was
      often incorrect. Given its high cost and limited clinical value, magnetic
      resonance imaging should not be used routinely as an adjunct to ultrasound in the
      diagnosis of placenta accreta spectrum until evidence for utility is clearly
      demonstrated by more definitive prospective studies.

PMID- 29572090
TI  - Compatibility between weak gel and microorganisms in weak gel-assisted microbial
      enhanced oil recovery.
AB  - To investigate weak gel-assisted microbial flooding in Block Wang Long Zhuang in
      the Jiangsu Oilfield, the compatibility of weak gel and microbe was evaluated
      using laboratory experiments. Bacillus sp. W5 was isolated from the formation
      water in Block Wang Long Zhuang. The rate of oil degradation reached 178 mg/day,
      and the rate of viscosity reduction reached 75.3%. Strain W5 could produce
      lipopeptide with a yield of 1254 mg/L. Emulsified crude oil was dispersed in the
      microbial degradation system, and the average diameter of the emulsified oil
      particles was 18.54 MUm. Bacillus sp. W5 did not affect the rheological
      properties of the weak gel, and the presence of the weak gel did not
      significantly affect bacterial reproduction (as indicated by an unchanged
      microbial biomass), emulsification (surface tension is 35.56 mN/m and average oil
      particles size is 21.38 MUm), oil degradation (162 mg/day) and oil viscosity
      reduction (72.7%). Core-flooding experiments indicated oil recovery of 23.6% when
      both weak gel and Bacillus sp. W5 were injected into the system, 14.76% when only
      the weak gel was injected, and 9.78% with strain W5 was injected without the weak
      gel. The results demonstrate good compatibility between strains W5 and the weak
      gel and highlight the application potential of weak gel-assisted microbial
      flooding.

PMID- 29572092
TI  - Model for End-Stage Liver Disease Excluding INR (MELD-XI) score is associated
      with hemodynamic impairment and predicts mortality in critically ill patients.
AB  - PURPOSE: We aimed (i) to evaluate Model for End-stage Liver Disease excluding INR
      (MELD-XI) score for prediction of mortality in a cohort of critically ill
      patients and (ii) to investigate associations of MELD-XI with microcirculation
      and (iii) to evaluate microcirculation for prediction of mortality in high-risk
      patients, e.g., with high MELD-XI scores. METHODS: 308 patients were included in
      our retrospective analysis, a subgroup of the multicenter micro-SOAP-study.
      Microcirculation was evaluated by Sidestream Dark Field (SDF) imaging. Evaluation
      of associations with mortality was done by logistic regression analysis, an
      optimal cut-off was calculated by means of the Youden Index. We divided the
      cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12
      score points). RESULTS: Patients with a MELD-XI > 12 points were of similar age
      (60 +/- 1 years vs 62 +/- 2 years; p = 0.32), but clinically sicker as mirrored
      by higher APACHE II scores (20 +/- 1 vs 16 +/- 1; p < 0.001). In the MELD-XI > 12
      cohort in-hospital mortality was significantly higher compared to the MELD <= 12
      group (48% vs 24%%; HR 2.98 95%CI 1.76-5.04; p = 0.003) and MELD-XI score was
      associated with mortality even after correction for relevant clinical confounders
      (HR 1.04 95%CI 1.01-1.07; p = 0.004) There were no associations between MELD-XI
      and parameters of microvascular perfusion. CONCLUSIONS: MELD-XI is associated
      with in-hospital mortality and constitutes a useful tool for risk stratification
      in intensive care medicine. Interestingly, there were no associations between
      MELD-XI and microcirculation. Possibly parameters of the microcirculation present
      an online tool of hemodynamic assessment while MELD-XI presents an assessment of
      already established organ failure.

PMID- 29572093
TI  - You can keep your shirt on: A physician's auscultating s(k)in.

PMID- 29572094
TI  - Hepatic-targeted RNA interference provides robust and persistent knockdown of
      alpha-1 antitrypsin levels in ZZ patients.
AB  - BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder
      causing pulmonary and liver disease. The PiZ mutation in AAT (SERPINA1) results
      in mis-folded AAT protein (Z-AAT) accumulating in hepatocytes, leading to
      fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z
      AAT might benefit patients with AATD-associated liver disease. This study
      evaluated an RNAi therapeutic to silence production of AAT. METHODS: Part A of
      this double-blind first-in-human study randomized 54 healthy volunteers (HVs)
      into single dose cohorts (two placebo: four active), receiving escalating doses
      of the investigational agent ARC-AAT from 0.38 to 8.0 mg/kg or placebo. Part B
      randomized 11 patients with PiZZ (homozygous for Z-AAT) genotype AATD, who
      received up to 4.0 mg/kg of ARC-AAT or placebo. Patients with baseline
      FibroScan(r) >11 kPa or forced expiratory volume in one second (FEV1) <60% were
      excluded. Assessments included safety, pharmacokinetics, and change in serum AAT
      concentrations. RESULTS: A total of 36 HVs received ARC-AAT and 18 received
      placebo (part A). Seven PiZZ individuals received ARC-AAT and four received
      placebo (part B). A dose response in serum AAT reduction was observed at doses
      >=4 mg/kg with similar relative reductions in PiZZ patients and HVs at 4 mg/kg
      and a maximum reduction of 76.1% (HVs) vs. 78.8% (PiZZ) at this dose. The time it
      took for serum AAT to return to baseline was similar for HV and PiZZ. There were
      no notable differences between HV and PiZZ safety parameters. The study was
      terminated early because of toxicity findings related to the delivery vehicle
      (ARC-EX1) seen in a non-human primate study. CONCLUSION: PiZZ patients and HVs
      responded similarly to ARC-AAT. Deep and durable knockdown of hepatic AAT
      production based on observed reduction in serum AAT concentrations was
      demonstrated. LAY SUMMARY: Accumulation of abnormal proteins in the livers of
      patients with alpha-1 antitrypsin deficiency may lead to decreased liver function
      and potentially liver failure. Therapeutics targeting the production of these
      abnormal proteins may be used to prevent or treat liver disease in patients with
      alpha-1 antitrypsin deficiency. CLINICAL TRIAL REGISTRATION NUMBER: NCT02363946.

PMID- 29572091
TI  - Effects on short term outcome of non-invasive ventilation use in the emergency
      department to treat patients with acute heart failure: A propensity score-based
      analysis of the EAHFE Registry.
AB  - OBJECTIVE: To assess the effects of non-invasive ventilation (NIV) in emergency
      department (ED) patients with acute heart failure (AHF) on short term outcomes.
      METHODS: Patients from the EAHFE Registry (a multicenter, observational,
      multipurpose, cohort-designed database including consecutive AHF patients in 41
      Spanish EDs) were grouped based on NIV treatment (NIV+ and NIV-groups). Using
      propensity score (PS) methodology, we identified two subgroups of patients
      matched by 38 covariates and compared regarding 30-day survival (primary
      outcome). Interaction was investigated for age, sex, ischemic cardiomyopathy,
      chronic obstructive pulmonary disease, AHF precipitated by an acute coronary
      syndrome (ACS), AHF classified as hypertensive or acute pulmonary edema (APE),
      and systolic blood pressure (SBP). Secondary outcomes were intensive care unit
      (ICU) admission; mechanical ventilation; in-hospital, 3-day and 7-day mortality;
      and prolonged hospitalization (>7 days). RESULTS: Of 11,152 patients from the
      EAHFE (age (SD): 80 (10) years; 55.5% women), 718 (6.4%) were NIV+ and had a
      higher 30-day mortality (HR = 2.229; 95%CI = 1.861-2.670) (p < 0.001). PS
      matching provided 2 groups of 490 patients each with no significant differences
      in 30-day mortality (HR = 1.239; 95%CI = 0.905-1.696) (p = 0.182). Interaction
      analysis suggested a worse effect of NIV on elderly patients (>85 years, p <
      0.001), AHF associated with ACS (p = 0.045), and SBP < 100 mmHg (p < 0.001). No
      significant differences were found in the secondary endpoints except for more
      prolonged hospitalizations in NIV+ patients (OR = 1.445; 95%CI = 1.122-1.862) (p
      = 0.004). CONCLUSION: The use of NIV to treat AHF in ED is not associated with
      improved mortality outcomes and should be cautious in old patients and those with
      ACS and hypotension.

PMID- 29572095
TI  - A simple diet- and chemical-induced murine NASH model with rapid progression of
      steatohepatitis, fibrosis and liver cancer.
AB  - BACKGROUND AND AIMS: Although the majority of patients with non-alcoholic fatty
      liver disease (NAFLD) have only steatosis without progression, a sizeable
      fraction develop non-alcoholic steatohepatitis (NASH), which can lead to
      cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse
      models for NASH require 24-52 weeks, which makes testing for drug response costly
      and time consuming. METHODS: We have sought to establish a murine NASH model with
      rapid progression of extensive fibrosis and HCC by using a western diet (WD),
      which is high-fat, high-fructose and high-cholesterol, combined with low weekly
      dose of intraperitoneal carbon tetrachloride (CCl4), which serves as an
      accelerator. RESULTS: C57BL/6J mice were fed a normal chow diet +/- CCl4 or WD +/
      CCl4 for 12 and 24 weeks. Addition of CCl4 exacerbated histological features of
      NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3
      fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver
      transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl4
      mice and immunologic features were similar to those of human NASH. CONCLUSIONS:
      Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and
      mimics histological, immunological and transcriptomic features of human NASH,
      suggesting that it will be a useful experimental tool for preclinical drug
      testing. LAY SUMMARY: A carefully characterized model has been developed in mice
      that recapitulates the progressive stages of human fatty liver disease, from
      simple steatosis, to inflammation, fibrosis and cancer. The functional pathways
      of gene expression and immune abnormalities in this model closely resemble human
      disease. The ease and reproducibility of this model make it ideal to study
      disease pathogenesis and test new treatments.

PMID- 29572097
TI  - Hippocampal microvasculature changes in association with oxidative stress in
      Alzheimer's disease.
AB  - Vascular endothelial dysfunction is a primary phenotype of aging, and
      microvascular (MV) lesion is mainly associated with Alzheimer's disease (AD).
      Here we have studied the correlation of MV wall thickness and CA1 pyramidal
      neuronal pathology in autopsy-confirmed AD brains. Both hyaline (h-MV) and
      increased cell number (c-MV) associated MV wall thickening was found in age
      matched control (AC) hippocampus without significant change in Abeta level (Braak
      stages 0-III). AC neurons neighboring the h-MV showed lower levels of oxidative
      DNA/RNA damage and Abeta precursor protein (APP), while the neurons around c-MV
      showed higher oxidative DNA/RNA damage with increased APP expression. Neurons in
      AC hippocampus without MV wall thickening (thin wall) showed increased DNA/RNA
      damage and APP levels compared to AC cases with h-MV and c-MV walls. In the AD
      hippocampus neurons neighboring h-MV walls showed increased levels of Abeta and
      decreased number of dendritic spines (at Braak stages IV-VI). C-MV neighboring
      neurons in the AD cases showed higher levels of DNA/RNA damage with increased APP
      at stages II - III, followed by lower levels of oxidative DNA/RNA damage,
      decreased APP and increased Abeta levels with loss of dendritic spines at stages
      IV-VI. Prolonged treatment of primary human fetal hippocampal neurons with tert
      butyl hydroperoxide (TBHP) induced oxidative DNA damage with a sustained increase
      in APP. Abeta increased rapidly and then decreased overtime. Short-term TBHP
      treated neurons showed lower levels of superoxide (O2* -) without significant DNA
      damage. Short-term TBHP treatment induced a gradual decrease in APP but an
      increase in Abeta levels over time. In conclusion this study indicates that AD
      hippocampus at Braak stages II-III are characterized by strong oxidative DNA/RNA
      damage with increased APP in neurons associated with c-MV, while stages IV-VI are
      characterized by a slow increase in Abeta in neurons neighboring both h-MV and c
      MV.

PMID- 29572098
TI  - Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer:
      Novel iron chelating agents to target p21 expression and activity.
AB  - Iron (Fe) has become an important target for the development of anti-cancer
      therapeutics with a number of Fe chelators entering human clinical trials for
      advanced and resistant cancer. An important aspect of the activity of these
      compounds is their multiple molecular targets, including those that play roles in
      arresting the cell cycle, such as the cyclin-dependent kinase inhibitor, p21. At
      present, the exact mechanism by which Fe chelators regulate p21 expression
      remains unclear. However, recent studies indicate the ability of chelators to up
      regulate p21 at the mRNA level was dependent on the chelator and cell-type
      investigated. Analysis of the p21 promoter identified that the Sp1-3-binding site
      played a significant role in the activation of p21 transcription by Fe chelators.
      Furthermore, there was increased Sp1/ER-alpha and Sp1/c-Jun complex formation in
      melanoma cells, suggesting these complexes were involved in p21 promoter
      activation. Elucidating the mechanisms involved in the regulation of p21
      expression in response to Fe chelator treatment in neoplastic cells will further
      clarify how these agents achieve their anti-tumor activity. It will also enhance
      our understanding of the complex roles p21 may play in neoplastic cells and lead
      to the development of more effective and specific anti-cancer therapies.

PMID- 29572096
TI  - SEXUAL DIMORPHISM IN SELENIUM METABOLISM AND SELENOPROTEINS.
AB  - Sexual dimorphism, the condition in which males and females in a species differ
      beyond the morphology of sex organs, delineates critical aspects of the biology
      of higher eukaryotes, including selenium metabolism. While sex differences in
      selenium biology have been described by several laboratories, delineation of the
      effects of sex in selenium function and regulation of selenoprotein expression is
      still in its infancy. This review encompasses the available information on sex
      dependent parameters of selenium metabolism, as well as the effects of selenium
      on sex hormones. Gaps in the current knowledge of selenium and sex are identified
      and discussed.

PMID- 29572099
TI  - A ten-year analysis of the reasons for death following ambulatory surgery: Nine
      closed claims declared to the SHAM insurance.
AB  - INTRODUCTION: The constant development of ambulatory surgery (AS) raises the
      problem of monitoring patients after discharge and the risk of death in the case
      of delays in the management of a serious complication. PATIENTS AND METHODS: The
      aim of this retrospective study was to describe the deaths observed within the 30
      day period following AS declared to the SHAM insurance (Societe hospitaliere
      d'assurance mutuelle) over the last 10 years. RESULTS: During the study period
      33,962 claims were surgery-related and 11 were for deaths after AS. Two of the
      death claims were excluded from our study because they occurred after the first
      month. The surgeries concerned were tonsilectomy (3), cataract (2), inguinal
      hernia (2), varicose vein stripping (1) and laparoscopy (1). Death occurred on
      average 5.4 days after the AS, in intensive care (3), during hospitalisation (2),
      with emergency medical services (1), in an emergency department (1) or at home
      (2). Anaesthesia was directly implicated in 3 cases: anaphylactic shock (Diamox),
      pneumoperitoneum (gastric swelling) and hemoperitoneum (mismanagement of
      anticoagulants). 1 case was due to a pulmonary embolism and 5 to a surgical
      cause. DISCUSSION-CONCLUSION: There was only one case where the complication was
      aggravated due to the delay of care provision and this was because of a lack of
      information on the complications requiring an emergency return (abdominal pain
      after laparoscopy). In all the other cases, death would also probably have
      occurred during conventional hospitalisation, either because it was unavoidable
      or because the patient was too far from the surgery.

PMID- 29572100
TI  - Glycaemic control in diabetic patient: Towards a global care of glycaemia.

PMID- 29572101
TI  - Impact of connecting continuous renal replacement therapy to the extracorporeal
      membrane oxygenation circuit.
AB  - PURPOSE: Continuous veno-venous haemofiltration (CVVH) directly connected to
      extracorporeal membrane oxygenation (ECMO) may ensure better blood flow and allow
      prolonged circuit life. The objective of this study was to assess circuit life of
      CVVH connected to ECMO and to a dialysis catheter. MATERIALS AND METHODS: In this
      prospective observational study, patients receiving CVVH via ECMO were compared
      to time-matched patients receiving CVVH via a conventional dialysis catheter.
      CVVH circuit life and the safety and efficacy of the two CVVH procedures were
      analysed. Time to event was estimated using Kaplan-Meier analysis and compared
      using the log-rank test. RESULTS: Seventeen patients were included in each group,
      with 43 sessions in the ECMO group and 56 sessions in the DC group. Median CVVH
      circuit life was 48 [21-72] vs 20 [6-39] hours in the ECMO and DC groups,
      respectively (relative risk of termination of the session: 2.4, 95% CI [1.41
      3.9], log rank P=0.0009). CVVH blood flow was higher in the ECMO group. Despite
      higher anticoagulant doses in the catheter group, the circuit clotting rate was
      lower in the ECMO group. Effluent volume was slightly higher in the ECMO group
      (39ml/kg/h [33-47] vs 34ml/kg/h [32-39]), but with no biological impact. CVVH via
      ECMO was well tolerated with no major drawbacks. CONCLUSIONS: In patients
      requiring ECMO, CVVH connected to ECMO instead of DC could be proposed as an
      alternative approach, allowing more stable blood flow and prolonged CVVH circuit
      life.

PMID- 29572102
TI  - Biochemical characterization of the Helicobacter pylori Cag Type 4 Secretion
      System protein CagN and its interaction partner CagM.
AB  - Highly virulent Helicobacter pylori strains contain the cag pathogenicity island
      (cagPAI). It codes for about 30 proteins forming a type IV secretion system
      (T4SS) which translocates the pro-inflammatory protein CagA into epithelial host
      cells. While CagA and various other Cag proteins have been extensively studied,
      several cagPAI proteins are poorly characterized or of unknown function. CagN
      (HP0538) is of unknown function but highly conserved in the cagPAI suggesting an
      important role. cagM (HP0537) is the first gene of the cagMN operon and its
      product is part of the CagT4SS core complex. Both proteins do not have detectable
      homologs in other type IV secretion systems. We have characterized the
      biochemical and structural properties of CagN and CagM and their interaction. We
      demonstrate by circular dichroism, Multi-Angle Light Scattering (MALS) and small
      angle X-ray scattering (SAXS) that CagN is a folded, predominantly monomeric
      protein with an elongated shape in solution. CagM is folded and forms
      predominantly dimers that are also elongated in solution. We found by various in
      vivo and in vitro methods that CagN and CagM directly interact with each other.
      CagM self-interacts stably with a low nanomolar KD and can form stable multimers.
      Finally, in vivo experiments show that deletion of CagM reduces the amounts of
      CagN and other outer CagPAI proteins in H. pylori cells.

PMID- 29572103
TI  - Event-related potential correlates of stimulus equivalence classes: A study of
      task order of the equivalence based priming probes with respect to the stimulus
      equivalence tests, and among the distinct trial types with each other.
AB  - This study investigates the influences of: 1) the task order of two stimulus
      equivalence classes (SEC) probes, and 2) the possible differences within the
      equivalence trial types. These factors were analyzed together on both behavioral
      and event-related potentials (ERP) data. Two groups of normal subjects
      participated in two successive sessions. In the first session, all participants
      were trained in the baseline relations among visual stimuli (pseudo-words). In
      the second session, one group performed the matching-to-sample (MTS) equivalence
      tests before the equivalence-relatedness-priming (EBRP) task, while the other
      group performed both tasks in reverse order. In the EBRP task related trial types
      included trained, symmetrical and equivalence relationships while the unrelated
      trial types included the same stimuli but without relationships. Event related
      potentials were recorded separately for related and unrelated conditions during
      the EBRP task. Results showed that response times to related trials were shorter
      than those to unrelated ones. At the electrophysiological level, two late
      waveforms were sensitive to the differences among the stimulus pairs of the EBRP
      task: Both waveforms were larger for the unrelated than the related conditions.
      Conversely, there were no main influences of the task order or of the trial types
      with each other. These results provide evidence that 1) the EBRP task exhibits
      priming effects among the SEC stimuli, 2) the behavioral and electrophysiological
      effects were similar regardless of whether the EBRP task was done before or after
      the MTS tests, and 3) there were no differences within the baseline and derived
      trial types in the EBRP task.

PMID- 29572104
TI  - Towards developing a model to study alcohol drinking and craving in female mice
      housed in automated cages.
AB  - It is about half a century ago when the so-called "Wise model" to study alcohol
      drinking behavior in rats was established. The model was based on voluntary
      intermittent access to increasing concentrations of alcohol. We aimed to
      establish a model of alcohol craving and used an extinction test on withdrawal
      days 1 and 10 to study motivation for alcohol. For this purpose, the alcohol
      drinking training was paired with light cues to establish conditioning. The
      extinction test was carried out without alcohol but in the presence of light cues
      and empty bottles. The outcome measures were number of visits, nosepokes, and
      licks in the conditioned corner where the number of nosepokes represents how much
      mice "want" alcohol and number of licks shows how much mice "like" alcohol. The
      number of nosepokes during withdrawal is a measure of craving. Late withdrawal
      craving was found when intermittent alcohol access was carried out in the
      automated cages. In this case, we observed a significant increase in the number
      of nosepokes on both withdrawal days 1 and 10 as compared to water control. The
      number of nosepokes in the withdrawal days did not correlate with alcohol dose,
      but number of nosepokes on withdrawal day 1 correlated with the number of
      nosepokes on the last training day. Although we did not observe incubation of
      alcohol craving after withdrawal, the craving was increased at the late time
      point. We conclude that we have established a new tool to study alcohol drinking
      behavior and craving in female mice.

PMID- 29572105
TI  - Behavioral and psychological symptoms of dementia (BPSD) and impaired cognition
      reflect unsuccessful neuronal compensation in the pre-plaque stage and serve as
      early markers for Alzheimer's disease in the APP23 mouse model.
AB  - Recent research on Alzheimer's disease (AD) focuses on processes prior to amyloid
      beta plaque deposition accounting for the progress of the disease. However, early
      mechanisms of AD are still poorly understood and predictors of the disease in the
      pre-plaque stage essential for initiating an early therapy are lacking.
      Behavioral and psychological symptoms of dementia (BPSD) and potentially impaired
      cognition may serve as predictors and early clinical diagnostic markers for AD.
      To investigate potential BPSD and cognitive impairments in association with
      neuronal cell development as such markers for AD in the pre-plaque stage, female
      APP23 mice at eight, 19 and 31 weeks of age and corresponding control animals
      were tested for BPSD (elevated zero maze; sucrose preference test), motor
      coordination (rotarod), spatial memory and reversal learning (Morris water maze)
      and hippocampal neurogenesis as a neuronal correlate for hippocampus-dependent
      behavior. To evaluate a potential therapeutic effect of physical, cognitive and
      social stimulation, animals were exposed to environmental enrichment (EE) for
      one, twelve or 24 weeks from five weeks of age. In APP23, decreased anxiety
      accompanied increased agitation from eight weeks of age. Impairment of spatial
      memory and learning flexibility prior to plaque deposition involved an
      insufficient use of spatial search strategies associated with an unsuccessful
      compensatory increase of neurogenesis. EE had an overall beneficial effect on
      behavior and neurogenesis and thus constitutes a therapeutic tool to slow disease
      progression. BPSD, cognition and associated impaired neurogenesis complement
      clinical diagnostic markers for pre-plaque AD and contribute to an early
      detection essential to halt disease progression.

PMID- 29572106
TI  - An integrated evidence-based targeting strategy for determining combinatorial
      bioactive ingredients of a compound herbal medicine Qishen Yiqi dripping pills.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Qishen Yiqi is a widely used Chinese herbal
      medicine formula with "qi invigorating and blood activating" property. Its
      dripping pill preparation (QSYQ) is a commercial herbal medicine approved by the
      China Food and Drug Administration (CFDA) in 2003 and is extensively used
      clinically to treat cardiovascular diseases, such as ischemic heart failure and
      angina pectoris, as well as for the secondary prevention of myocardial
      infarction. However, the bioactive ingredients of QSYQ remain unclear. As QSYQ is
      a compound herbal formula, it is of great importance to elucidate its
      pharmacologically active ingredients and underlying synergetic effects. AIM OF
      THE STUDY: This experimental study was conducted to comprehensively determine the
      combinatorial bioactive ingredients (CBIs) in QSYQ and to elucidate their
      potential synergetic effects. The established strategy may shed new light on how
      to rapidly determine CBIs in complex herbal formulas with holistic properties.
      MATERIALS AND METHODS: An integrated evidence-based targeting strategy was
      introduced and validated to determine CBIs in QSYQ. The strategy included the
      following steps: (1) Chemical ingredients in QSYQ were analyzed via UPLC-Q-TOF/MS
      in the negative and positive modes and were identified by comparison with
      standard compounds and previously reported data. Their potential therapeutic
      activities were predicted based on the ChEMBL database to preliminarily search
      for candidate bioactive ingredients, and their combination was defined as the
      CBIs. (2) The CBIs were directly trapped and prepared from QSYQ with a two
      dimensional chromatographic separation system, and the remaining part was defined
      as the rest ingredients (RIs). (3) As animal and cell models, left anterior
      descending coronary artery ligation (LAD)-induced heart failure in rats and
      hypoxia-induced cardiac myocyte injury in H9c2 cells were applied to compare the
      potency of QSYQ, CBIs and RIs. (4) The synergetic effects on cardiac myocyte
      protection of multiple ingredients in CBIs were examined in this cell model.
      RESULTS: (1) Forty-three ingredients in QSYQ were identified via UPLC-Q-TOF/MS.
      Based on evidence-based screening using the ChEMBL database, 24 ingredients were
      predicted to be bioactive ingredients, and their combination was considered the
      CBIs. (2) The CBIs and RIs were successfully prepared according to a two
      dimensional chromatographic system. The CBIs were directly trapped and knocked
      out from QSYQ by hydrophilic interaction liquid chromatography coupled with
      reverse-phase liquid chromatography. The remaining part was used as RIs. (3) The
      results from pharmacological evaluation revealed that CBIs and QSYQ, but not RIs,
      significantly prevented myocardium injury; improved the ejection fraction (EF)
      and fractional shortening (FS); decreased the release of cardiac enzymes,
      including CK, CK-MB, and LDH; alleviated mitochondrial dysfunction; and protected
      the cell nucleus number and mitochondrial mass. Furthermore, QSYQ and CBIs
      possessed similar potency. (4) In hypoxia-stimulated H9c2 cells, CBIs showed far
      greater potency regarding the protection of cardiac myocyte injury than the
      individual ingredients in QSYQ, exhibiting obvious synergetic effects.
      CONCLUSIONS: An integrated evidence-based targeting strategy was successfully
      established and validated to determine CBIs from QSYQ with excellent efficiency.
      Importantly, the holistic property of QSYQ was retained in the CBIs. Hence, this
      study may shed new light on how to rapidly reveal combinatorial bioactive
      ingredients from complex prescriptions and will be greatly helpful in the
      establishment of an appropriate approach to quality control for herbal medicines.

PMID- 29572107
TI  - Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With
      Graft-versus-Host Disease.
AB  - PURPOSE: To compare the response of dry eye disease (DED) to treatment with
      topical steroid in patients with and without graft-vs-host disease (GVHD).
      DESIGN: Post hoc analysis of a double-masked, randomized clinical trial. METHODS:
      This single-center study included 42 patients with moderate-to-severe DED
      associated with (n = 21) or without (n = 21) chronic GVHD. In each group,
      patients received either loteprednol etabonate 0.5% ophthalmic suspension or
      artificial tears twice daily for 4 weeks. Clinical data, including Ocular Surface
      Disease Index (OSDI) questionnaire, corneal fluorescein staining (CFS),
      conjunctival lissamine green staining, tear break-up time (TBUT), and Schirmer
      test, were evaluated before and after treatment. RESULTS: There were no
      significant differences in signs and symptoms of DED between the groups at
      baseline. In non-GVHD patients receiving loteprednol treatment, the average OSDI
      score decreased by 34% from 49.5 +/- 5.9 to 32.6 +/- 4.8 (mean +/- standard error
      of the mean, P = .001) and the average CFS score decreased by 41% from 5.6 +/-
      0.6 to 3.3 +/- 0.9 (P = .02). On the other hand, loteprednol treatment in GVHD
      patients resulted in minimal change in OSDI (59.2 +/- 6.7 to 61.1 +/- 7.1, 3%
      increase, P = .66) and CFS (5.5 +/- 0.5 to 5.3 +/- 1.1, 4% decrease, P = .85)
      scores. Treatment with artificial tears resulted in 22% decrease of OSDI (P =
      .10) and 32% decrease of CFS (P = .02) scores in non-GVHD patients, and had
      minimal effect in patients with GVHD. CONCLUSIONS: DED patients with ocular GVHD
      have a less favorable response to a low-dose topical steroid regimen compared
      with those without ocular GVHD even with similar baseline disease severity.

PMID- 29572108
TI  - Establishment of the 1st WHO International Standard for anti-EV71 serum (Human).
AB  - Enterovirus A71 (EV71) is the major causative agent of severe and fatal hand,
      foot and mouth disease. There is plenty of evidence that EV71 has circulated
      widely in the Western Pacific Region for the last twenty years. Vaccines against
      EV71 are already available or under development. A collaborative study to
      establish the 1st WHO International Standard for anti-EV71 serum (Human) was
      conducted to ensure that methods used to measure the serum neutralizing activity
      or antibody levels against EV71 are accurate, sensitive and reproducible. Two
      candidate samples as well as a third candidate reference containing low anti-EV71
      antibody titre were produced from plasma samples donated by healthy individuals.
      All three serum samples exhibited good levels of neutralizing antibodies against
      a wide range of EV71 strains of various genotypes. The study showed that between
      laboratory variations in neutralization titres were significantly reduced when
      values were expressed relative to those of either of the two candidate sera.
      Sample 14/140 was established as the WHO 1st International Standard for anti-EV71
      serum (human), 14/138 as its potential replacement and 13/238 as a WHO Reference
      Reagent, with assigned unitage of 1,000, 1090 and 300 International Units (IU) of
      anti-EV71 neutralizing antibodies per ampoule, respectively.

PMID- 29572109
TI  - N-Docosahexaenoylethanolamine: A neurotrophic and neuroprotective metabolite of
      docosahexaenoic acid.
AB  - N-Docosahexaenoylethanolamine (synaptamide) is an endocannabinoid-like metabolite
      endogenously synthesized from docosahexaenoic acid (DHA, 22:6n-3), the major
      omega-3 polyunsaturated fatty acid present in the brain. Although its
      biosynthetic mechanism has yet to be established, there is a closely linked
      relationship between the levels of synaptamide and its precursor DHA in the
      brain. Synaptamide at nanomolar concentrations promotes neurogenesis, neurite
      outgrowth and synaptogenesis in developing neurons. Synaptamide also attenuates
      the lipopolysaccharide-induced neuroinflammatory response and reduces the
      deleterious effects of ethanol on neurogenic differentiation of neural stem cells
      (NSCs). These actions are mediated by a specific target receptor of synaptamide
      GPR110 (ADGRF1), a G-protein coupled receptor that is highly expressed in NSCs
      and the brain during development. Synaptamide binding to GPR110 induces cAMP
      production and phosphorylation of protein kinase A (PKA) and the cAMP response
      element binding protein (CREB). This signaling pathway leads to the expression of
      neurogenic and synaptogenic genes and suppresses the expression of
      proinflammatory genes. The GPR110-dependent cellular effects of synaptamide are
      recapitulated in animal models, suggesting that synaptamide-derived mechanisms
      may have translational implications. The synaptamide bioactivity transmitted by
      newly deorphanized GPR110 provides a novel target for neurodevelopmental and
      neuroprotective control as well as new insight into mechanisms for DHA's
      beneficial effects on the central nervous system.

PMID- 29572110
TI  - Biological activities of non-enzymatic oxygenated metabolites of polyunsaturated
      fatty acids (NEO-PUFAs) derived from EPA and DHA: New anti-arrhythmic compounds?
AB  - omega3 Polyunsaturated fatty acids (omega3 PUFAs) have several biological
      properties including anti-arrhythmic effects. However, there are some evidences
      that it is not solely omega3 PUFAs per se that are biologically active but the
      non-enzymatic oxygenated metabolites of polyunsaturated fatty acids (NEO-PUFAs)
      like isoprostanes and neuroprostanes. Recent question arises how these molecules
      take part in physiological homeostasis, show biological bioactivities and anti
      inflammatory properties. Furthermore, they are involved in the circulations of
      childbirth, by inducing the closure of the ductus arteriosus. In addition,
      oxidative stress which can be beneficial for the heart in given environmental
      conditions such as the presence of omega3 PUFAs on the site of the stress and the
      signaling pathways involved are also explained in this review.

PMID- 29572111
TI  - Comparative Analysis of Flow Cytometry and RQ-PCR for the Detection of Minimal
      Residual Disease in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
      after Hematopoietic Stem Cell Transplantation.
AB  - The aim of this study was to examine the value of minimal residual disease (MRD)
      detection by multiparameter flow cytometry (MFC) and real-time quantitative PCR
      (RQ-PCR) at the early stage after hematopoietic stem cell transplantation for
      predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome
      positive acute lymphoblastic leukemia (Ph+-ALL). Patients who maintained complete
      molecular remission (BCR-ABL <.01%) status at 1 and 3 months were associated with
      a lower relapse rate (P = .02 and <.001) and better LFS (P = .014 and .013) than
      were those without a complete molecular remission. Negative MFC at 1, 2, and 3
      months was associated with a lower relapse rate (P = .01, .004, and .04,
      respectively) and better LFS (P = .044, <.0001, and .013, respectively).
      Multivariate analysis showed that MRD positivity identified by MFC or RQ-PCR at 3
      months was an independent risk factor for relapse (hazard ratio [HR], 6.042 (95%
      confidence interval [CI], 2.283 to 15.988), P < .001), LFS (HR, 3.614 (95% CI,
      1.610 to 8.111), P = .002), and overall survival (HR, 2.547, 95% CI, 1.008 to
      6.443), P = .048). In summary, MRD detection by MFC and RQ-PCR detection of BCR
      ABL at the early stage were important predictors of outcome in patients with Ph+
      ALL, and these tests played complementary roles in predicting prognosis.

PMID- 29572112
TI  - An automated Monte Carlo QC system for volumetric modulated arc therapy:
      Possibilities and challenges.
AB  - PURPOSE: To develop and implement an automated Monte Carlo (MC) system for
      patient specific VMAT quality control in a patient geometry that generates
      treatment planning system (TPS) compliant DICOM objects and includes a module for
      3D analysis of dose deviations. Also, the aims were to recommend diagnose
      specific tolerance criteria and an evaluation procedure. METHODS: The EGSnrc code
      package formed the basis for development of the MC system. The workflow consists
      of a number of modules connected to a TPS by means of manual DICOM exports and
      imports which were executed sequentially without user interaction. DVH comparison
      was performed in the TPS. In addition, MC- and TPS dose distributions were
      analysed by applying the normalized dose difference (NDD) formalism. NDD failure
      maps and a pass rate for a certain threshold were obtained. 170 clinical plans
      (prostate, thorax, head-and-neck and gynecological) were selected for analysis.
      RESULTS: Agreement within 1.5% was found between clinical- and MC data for the
      mean dose to the target volumes and within 3% for parameters more sensitive to
      the shape of the DVH e.g. D98% PTV. Regarding the NDD analysis, tolerance
      criteria 2%/3 mm were established for prostate plans and 3%/3 mm for the rest of
      the cases. CONCLUSIONS: An automated MC system was developed and implemented.
      Evaluation procedure is recommended with NDD-analysis as a first step. For pass
      rate < 95%, the evaluation continues with comparison of DVH parameters. For
      deviations larger than 2%, a visual inspection of the clinical- and MC dose
      distributions is performed.

PMID- 29572113
TI  - Long-term results of hand-assisted laparoscopic gastrectomy for advanced Siewert
      type II and type III esophagogastric junction adenocarcinoma.
AB  - BACKGROUND: Hand-assisted laparoscopic surgery (HALS) combines laparoscopic
      surgery with the tactile feedback of a hand-assist device for complex
      laparoscopic operations. This study aimed to comparatively evaluate the long-term
      outcomes of patients who underwent HALS versus open surgery for the treatment of
      advanced Siewert type II and type III adenocarcinoma of the esophagogastric
      junction (AEG). METHODS: A retrospective analysis of 77 patients with advanced
      Siewert type II and IIIAEG between March 2010 and March 2011. Data concerning the
      basic characteristics of patients, pathological staging, early postoperative
      course, and long-term follow-up were collected and analyzed. RESULTS: HALS
      resulted in significantly lower mean blood loss and mean postoperative hospital
      stay in comparison to open surgery (P = 0.007 and 0.01, respectively). The mean
      number of resected lymph nodes was 23.22 +/- 9.36 in the HALS group, which was
      more than in the open surgery group (18.61 +/- 6.91, P = 0.015). The cumulative 5
      year overall survival (OS) rate was 52.8% (95% CI 43.07-60.09) for all patients
      in the HALS group (78.6% for stage II patients and 36.4% for stage III patients).
      The 5-year OS rate was not significantly different between both groups.
      CONCLUSIONS: While achieving similar oncological outcomes to open surgery, the
      HALS approach resulted in reduced blood loss, shortened postoperative hospital
      stay, and the resection of more lymph nodes. This analysis suggests that HALS may
      serve as a less invasive and as successful alternative to open surgery for the
      treatment of advanced Siewert type II and type IIIAEG.

PMID- 29572114
TI  - Renal outcomes with sodium glucose cotransporter 2 (SGLT2) inhibitor,
      dapagliflozin, in obese insulin-resistant model.
AB  - A growing body of evidence indicates that obesity and insulin resistance
      contribute to the progression of renal disease. This study was performed to
      determine the effects of dapagliflozin, a novel sodium glucose cotransporter 2
      (SGLT2) inhibitor, on renal and renal organic anion transporter 3 (Oat3)
      functions in high-fat diet fed rats, a model of obese insulin-resistance. Twenty
      four male Wistar rats were divided into two groups, and received either a normal
      diet (ND) (n = 6) or a high-fat diet (HFD) (n = 18) for 16 weeks. At week 17, the
      HFD-fed rats were subdivided into three subgroups (n = 6/subgroup) and received
      either a vehicle (HFD), dapagliflozin (HFDAP; 1.0 mg/kg/day) or metformin (HFMET;
      30 mg/kg/day), by oral gavage for four weeks. Metabolic parameters, renal
      function, renal Oat3 function, renal oxidative stress, and renal morphology were
      determined. The results showed that obese insulin-resistant rats induced by HFD
      feeding had impaired renal function and renal Oat3 function together with
      increased renal oxidative injury. Dapagliflozin or metformin treatment decreased
      insulin resistance, hypercholesterolemia, creatinine clearance and renal
      oxidative stress leading to improved renal function. However, dapagliflozin
      treatment decreased blood pressure, serum creatinine, urinary microalbumin and
      increased glucose excretions, and showed a greater ability to ameliorate impaired
      renal insulin signaling and glomerular barrier damage than metformin. These data
      suggest that dapagliflozin had greater efficacy than metformin for attenuating
      renal dysfunction and improving renal Oat3 function, at least in part by reducing
      renal oxidative stress and modulating renal insulin signaling pathways, and hence
      ameliorating renal injury.

PMID- 29572115
TI  - Low galactosylation of IgG associates with higher risk for future diagnosis of
      rheumatoid arthritis during 10 years of follow-up.
AB  - Antibodies are known to have an important role in the development of rheumatoid
      arthritis (RA), one of the most prevalent chronic inflammatory diseases which
      primarily involves the joints. Most RA patients develop autoantibodies against
      immunoglobulin G (IgG) and changes in IgG glycosylation have been associated with
      RA. We undertook this study to determine whether altered IgG glycosylation
      precedes the disease diagnosis. We studied IgG glycosylation in RA in two
      prospective cohorts (N = 14,749) by measuring 28 IgG glycan traits in 179
      subjects who developed RA within 10-years follow-up and 358 matched controls.
      Ultra-performance liquid chromatography method based on hydrophilic interactions
      (HILIC-UPLC) was used to analyse IgG glycans. Future RA diagnosis associated with
      traits related to lower galactosylation and sialylation of IgG when comparing the
      cases to the matched controls. In RA cases, these traits did not correlate with
      the time between being recruited to the study and being diagnosed with RA (median
      time 4.31 years). The difference in IgG glycosylation was relatively stable and
      present years before diagnosis. This indicates that long-acting factors affecting
      IgG glycome composition are among the underlying mechanisms of RA and that
      decreased galactosylation is a pre-existing risk factor involved in the disease
      development.

PMID- 29572116
TI  - Effect of irradiation-induced intercellular adhesion molecule-1 expression on
      natural killer cell-mediated cytotoxicity toward human cancer cells.
AB  - BACKGROUND AIMS: Irradiation enhances the adhesion between natural killer (NK)
      cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM
      1) on target cells. Therefore, we investigated the effect of irradiation-induced
      ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity.
      METHODS: Expression levels of ICAM-1 on the target cell surface before and after
      irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and
      U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human
      peripheral blood mononuclear cells was performed by co-culture with irradiated
      K562 cells. The related adhesion molecule lymphocyte function-associated antigen
      1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked
      immunosorbent assay was used to detect interferon-gamma (IFN-gamma), and WST-8
      assays were performed to check NK cell cytotoxicity. Finally, blocking assays
      were performed using monoclonal antibodies against ICAM-1 or LFA-1. RESULTS: LFA
      1 expression increased on NK cells after expansion (P <0.001). The expression of
      ICAM-1 was significantly upregulated by irradiation after 24 h in various cell
      lines, including HL60 (P <0.001), SKBR-3 (P <0.001), T47D (P <0.001) and U937 (P
      <0.001), although the level of expression depended on the cell line. ICAM-1
      expression was extremely low before and after irradiation in U251 cells. NK cell
      mediated cytotoxicity increased after irradiation of HL60 (P <0.001), SKBR-3 (P
      <0.001), T47D (P = 0.003), and U937 (P = 0.004) cells, in which ICAM-1 expression
      was significantly increased after irradiation. IFN-gamma production by NK cells
      in response to HL60 (P <0.001) and T47D (P = 0.011) cells significantly increased
      after irradiation. NK cell-mediated cytotoxicity against irradiated SKBR-3 (P
      <0.001) and irradiated T47D cells (P = 0.035) significantly decreased after
      blocking of ICAM-1. Blocking of LFA-1 on NK cells resulted in reduced
      cytotoxicity against irradiated HL60 (P <0.001) and irradiated SKBR-3 (P <0.001).
      CONCLUSIONS: Irradiation upregulates ICAM-1 expression on the surface of human
      cancer cells and enhances activated NK cell-mediated cytotoxicity. Therefore,
      irradiation combined with NK cell therapy may improve the antitumor effects of NK
      cells.

PMID- 29572117
TI  - Smad4/Fascin index is highly prognostic in patients with diffuse type EBV
      associated gastric cancer.
AB  - Gastric cancer is a heterogeneous disorder for which predicting clinical outcomes
      is challenging, although various biomarkers have been suggested. The Smad4 and
      Fascin proteins are known prognostic indicators of different types of malignancy.
      Smad4 primarily functions as a key regulator of tumor suppression, whereas Fascin
      exhibits oncogenic function by enhancing tumor infiltration. A combined marker
      based on these opposing roles may improve prognostic accuracy in gastric cancer.
      Smad4 and Fascin expression was assessed in tissue microarrays obtained from 285
      primary gastric adenocarcinoma, 201 normal tissue, and 51 metastatic
      adenocarcinoma samples. A Smad4/Fascin index based on the relative expression of
      each protein was divided into low- and high-expression groups using receiver
      operating characteristic curves. We compared normal tissue, primary
      adenocarcinoma, and metastatic adenocarcinoma in Smad4 and Fascin expression and
      the differences in clinicopathological findings between low Smad4/Fascin and high
      Smad4/Fascin expression in gastric adenocarcinoma. High Smad4/Fascin expression
      was significantly associated with worse outcomes, such as old age, advanced T and
      N category, large tumor size, high histological grade, lymphatic and vascular
      invasion, and presence of Epstein-Barr virus (EBV) (all p < 0.05). Univariate and
      multivariate analyses revealed a significant relationship between disease-free or
      overall survival and Smad4/Fascin index in diffuse-type or EBV-associated gastric
      cancer (all p < 0.05). A dual marker system using Smad4 and Fascin may be a
      reliable indicator for predicting clinical outcomes in patients with diffuse-type
      or EBV-associated gastric cancer.

PMID- 29572118
TI  - Intradepartmental consultations in surgical pathology: Review of a standardized
      process and factors influencing consultation rates and practices in an academic
      and community hospital setting.
AB  - Intradepartmental consultations (ICs) are important for quality assurance (QA)
      and ensuring diagnostic accuracy in surgical pathology. Few studies have reviewed
      pathologist factors that influence IC rates. Our study reviews IC data and
      factors that influence both formal (written) and informal (verbal) consultation
      practices among pathologists in academic and community hospital settings. Formal
      IC records from the academic hospital were collected and academic and community
      pathologists were invited to complete a survey about their IC practices. All
      centers had a formalized process for documenting ICs; however, 92% of academic
      and 90% of community pathologists also requested informal IC. The top reasons for
      selecting a particular colleague for IC was perceived level of expertise;
      however, interpersonal relationships and office proximity had a greater impact on
      informal IC practice. Top reasons for requesting a formal IC were mandatory
      (subspecialty defined) consultation and uncertainty regarding pathological
      findings. Advice on wording was a common reason for informal IC. Written
      documentation of IC aids in QA and determination of IC metrics; however,
      informal, undocumented ICs still occur. Reasons for IC and choice of consulting
      pathologist are multifactorial, and identifying these can help target quality
      improvement initiatives.

PMID- 29572119
TI  - Bex1 attenuates neuronal apoptosis in rat intracerebral hemorrhage model.
AB  - Brain expressed x-linked gene 1 (Bex1) which is at high levels in several
      populations of central nervous system (CNS) neurons, belongs to a family of small
      proteins of unknown function, playing roles as adaptors or modulators of
      intracellular signaling pathways. But its distribution and function in CNS
      remains unclear. Neuronal apoptosis is the major pathogenesis in secondary brain
      injury of intracerebral hemorrhage (ICH). In this study, the roles of Bex1 were
      explored in the pathophysiology of ICH. Western blot, immunohistochemistry, and
      immunofluorescence showed that obvious up-regulation of Bex1 in neurons adjacent
      to the hematoma after ICH. Furthermore, the increase of Bex1 expression was
      accompanied by the enhanced expression of Bax and active caspase-3, and decreased
      expression of B-cell lymphoma 2 (Bcl-2) following ICH. The in vitro study using
      Bex1 siRNA transfection in hemin-exposed PC12 cells suggested that Bex1 exerted
      anti-apoptotic function. Therefore, Bex1 may play the neuronal anti-apoptosis
      role following ICH, implying a novel molecular target for the therapy of ICH.

PMID- 29572120
TI  - VEGFR-2 as a novel predictor of survival in gastric cancer: A systematic review
      and meta-analysis?.
AB  - BACKGROUND: Expression of VEGFRs may affect cancer prognosis. The aim of this
      work is to evaluate the prognostic significance of VEGFRs of patients with
      gastric cancer. METHODS: The databases PubMed, Embase, Web of Science, and
      Cochrane Library as well as ASCO and ESMO were searched systematically for
      articles reporting the prognostic significance of tissue VEGFRs in gastric
      cancer. The statistical analyses were carried out using Stata version 12.0.
      RESULTS: A total of 8 articles comprising 950 patients were eligible for meta
      analysis. The combined HR of studies evaluating total VEGFRs overexpression was
      1.42 (95% CI 1.01-2.00, P = 0.044), suggesting that it had prognosis significance
      in overall survival of gastric cancer. Subgroup analysis showed that it was VEGFR
      2 (HR 1.81, 95% CI 1.31-2.49, P < 0.001) but not VEGFR-3 (HR 0.91, 95% CI 0.45
      1.82, P = 0.787) overexpression was associated with an increased risk of median
      overall survival (mOS) and it can be a potentially predictive biomarker for
      gastric cancer. CONCLUSIONS: VEGFR-2 overexpression is a promising negative
      prognosis predictor for patients with gastric cancer. The prognosis significance
      of VEGFR-3 still need further study.

PMID- 29572121
TI  - Prognostic significance of epithelial-mesenchymal transition phenotypes in upper
      urinary tract urothelial carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) is a process which epithelial cells gain
      mesenchymal phenotype such as motility and invasiveness. We investigated the role
      of EMT in upper urinary tract urothelial carcinoma (UTUC). The patient cohort
      included 93 cases of UTUC treated with radical nephroureterectomy. Tissue
      microarrays were constructed from formalin-fixed paraffin-embedded tissue blocks.
      Immunohistochemical staining was performed for E-cadherin, vimentin, and smooth
      muscle actin to evaluate the EMT status. Interpretation criteria were defined for
      the staining results and EMT phenotypes were assigned as wild type, incomplete
      type (loss of E-cadherin and negative for vimentin), and complete type (loss of E
      cadherin and positive for vimentin). The loss of E-cadherin and vimentin
      expression was observed in 76 (81.7%) and 10 (10.8%) cases, respectively,
      yielding EMT phenotypes comprised of 17 cases (18.3%) of wild type, 66 cases
      (71.0%) of incomplete type, and 10 cases (10.8%) of complete types. In survival
      analyses, wild type showed statistically significant association with longer
      extra-bladder recurrence free survival (p < .001) and overall survival (p <
      .001). In multivariate analyses, complete type was an independent prognostic
      factor for extra-bladder recurrence free survival and overall survival. EMT
      phenotype based on the combination of EMT-related markers may provide a useful
      prognostic marker for UTUC patients.

PMID- 29572122
TI  - HPV infection and p16INK4A and TP53 expression in rare cancers of the uterine
      cervix.
AB  - Cervix cancer remains among most commonly diagnosed cancer in developing
      countries. Except squamous cell carcinoma and adenocarcinoma, the etiopathology
      and oncogenic mechanisms of rare cancers remain largely unknown. The study was
      performed to investigate the value of HPV infection and the expression of
      p16INK4A and TP53 in rare primitive cancers of the cervix. We conducted a
      retrospective study of rare primitive cancers of the cervix. Main
      clinicopathological features were reported. HPV infection was detected by in situ
      hybridization. Expression of p16INK4A and TP53 was analyzed by
      immunohistochemistry. Overall, seven cases were identified, including basaloid
      squamous cell carcinoma (BSCC, n = 2), small cell neuroendocrine carcinoma
      (SCNEC), granulocytic sarcoma without acute myeloid leukemia, leiomyosarcoma,
      primitive neuroectodermal tumor and botryoid-type embryonic rhabdomyosarcoma. The
      mean age of patients was 53.7 years. Four cancers were diagnosed at advanced
      stages. The prognosis was unfavorable and associated with patient death in five
      cases. HPV types 16/18 were detected in BSCCs and SCNEC. Strong and diffuse
      p16INK4A overexpression was described in the nucleus and the cytoplasm of all
      tumor cells of BSCCs and SCNEC. The remaining cancers exhibited only scattered
      and focal p16INK4A staining. Mutated TP53 protein was detected in BSCC (case 1)
      and GS. Rare cancers of the cervix are aggressive and associated with poor
      prognosis. In contrast to mesenchymal tumors, BSCCs and SCNEC are etiologically
      related to high-risk HPV infection and could be identified by block positive
      p16INK4A overexpression as common cancers of the cervix. TP53 mutations are not a
      negligible genetic event in rare cervical cancers.

PMID- 29572123
TI  - Clinical and electrocardiographic presentations of transient trifascicular block
      in three cats.
AB  - This report describes transient trifascicular block in three cats presented with
      lethargy and inappetence, and elevated cardiac troponin I concentrations. The
      electrocardiogram (ECG) of cat 1 showed a sinus rhythm with pronounced first
      degree atrioventricular (AV) block, right bundle branch block, and left anterior
      fascicular block. The ECG of cat 2 showed truncular left bundle branch block
      alternating with left anterior fascicular block coupled with prolonged PR
      intervals, second-degree heart block, and paroxysmal third-degree AV block. The
      ECG of cat 3 showed first-degree AV block with concomitant right bundle branch
      block. The diagnosis of trifascicular block was made when paroxysmal third-degree
      AV block was documented. All cats recovered with medical management within weeks.
      Each cat resumed a sinus rhythm. Elevated cardiac troponin I concentrations
      suggested myocarditis that improved.

PMID- 29572124
TI  - Short-interval and long-interval intracortical inhibition of TMS-evoked EEG
      potentials.
AB  - BACKGROUND: Inhibition in the human motor cortex can be probed by means of paired
      pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2-3
      ms (short-interval intracortical inhibition, SICI) or ~100 ms (long-interval
      intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as
      motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological
      experiments indicate that they are mediated by GABAA and GABAB receptors,
      respectively. OBJECTIVE/HYPOTHESIS: SICI and LICI of TMS-evoked EEG potentials
      (TEPs) and their pharmacological properties have not been systematically studied.
      Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS
      evoked TEPs, to investigate its pharmacological manipulation and to compare SICI
      with our previous results on LICI. METHODS: PpTMS-EEG was applied to the left
      motor cortex in 16 healthy subjects in a randomized, double-blind placebo
      controlled crossover design, testing the effects of a single oral dose 20 mg of
      diazepam, a positive modulator at the GABAA receptor, vs. 50 mg of the GABAB
      receptor agonist baclofen on SICI of TEPs. RESULTS: We found significant SICI of
      the N100 and P180 TEPs prior to drug intake. Diazepam reduced SICI of the N100
      TEP, while baclofen enhanced it. Compared to our previous ppTMS-EEG results on
      LICI, the SICI effects on TEPs, including their drug modulation, were largely
      analogous. CONCLUSIONS: Findings suggest a similar interaction of paired-pulse
      effects on TEPs irrespective of the interstimulus interval. Therefore, SICI and
      LICI as measured with TEPs cannot be directly derived from SICI and LICI measured
      with MEPs, but may offer novel insight into paired-pulse responses recorded
      directly from the brain rather than muscle.

PMID- 29572125
TI  - Hemoglobin, iron, vitamin B12, and folic acid deficiencies and
      hyperhomocysteinemia in Behcet's disease patients with atrophic glossitis.
AB  - BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous
      stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study
      mainly assessed whether 30 AG-positive RAS/BD (AG+RAS/BD) patients had
      significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid
      deficiencies and of hyperhomocysteinemia than 33 AG-negative RAS/BD (AG?RAS/BD)
      patients or 126 age- and sex-matched healthy control subjects. METHODS: The blood
      hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations were
      measured and compared among 30 AG+RAS/BD patients, 33 AG?RAS/BD patients, and 126
      healthy control subjects. RESULTS: We found that 43.3%, 33.3%, 13.3%, 6.7%, and
      20.0% of 30 AG+RAS/BD patients and 18.2%, 36.4%, 0%, 6.1%, and 9.1% of 33
      AG?RAS/BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies
      and hyperhomocysteinemia, respectively. Moreover, 30 AG+RAS/BD patients had
      significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid
      deficiencies and of hyperhomocysteinemia than healthy control subjects (all P
      values < 0.05), and had a higher frequency of hemoglobin deficiency (P = 0.058,
      marginal significance) and a significantly higher frequency of vitamin B12
      deficiency (P = 0.046) than 33 AG?RAS/BD patients. In addition, the 33 AG?RAS/BD
      patients had significantly higher frequencies of hemoglobin and iron deficiencies
      than healthy control subjects (both P-values < 0.001). CONCLUSION: We conclude
      that AG+RAS/BD patients do have significantly higher frequencies of hemoglobin,
      iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than
      healthy control subjects and have significantly higher frequencies of hemoglobin
      and vitamin B12 deficiencies than AG?RAS/BD patients.

PMID- 29572126
TI  - Bone health during endocrine therapy for cancer.
AB  - Preservation of bone health remains a long-term clinical challenge in patients
      with breast and prostate cancer. Osteoporosis, defined by a loss of bone mass and
      microarchitecture, often results in fragility fractures that are typically
      associated with a high socioeconomic burden. Endocrine therapy, a mainstay
      treatment in the management of patients with hormone-sensitive breast and
      prostate cancer in the adjuvant setting, commonly exerts adverse effects on the
      musculoskeletal system and is associated with an increased risk of osteoporosis
      and fractures. Adjuvant use of gonadotropin-releasing hormone analogues, which
      can also be used in metastatic disease, in combination with tamoxifen in
      premenopausal women, and aromatase inhibitors in postmenopausal women with
      hormone-sensitive breast cancer, causes rapid bone loss and fragility fractures.
      By contrast, selective oestrogen receptor modulators, such as tamoxifen, have
      bone-protective effects in postmenopausal women. In men with castration-sensitive
      prostate cancer, androgen deprivation is achieved with drugs that lower
      gonadotropin levels, and these drugs can be combined with androgen receptor
      antagonists. These therapies induce a high bone turnover with rapid bone loss
      that is reminiscent of the changes occurring in early menopause and result in an
      increased risk of fracture. In this Review, we describe how adjuvant endocrine
      therapies of breast and prostate cancer impair bone health and outline evidence
      from randomised controlled trials of strategies to reduce risk of fracture.

PMID- 29572127
TI  - Quantification of proteins by data independent acquisition: Performance
      assessment of the Hi3 methodology.
AB  - Proteomics greatly benefited from the development of mass spectrometry. Over the
      last years, data-independent acquisitions increased in popularity in an effort to
      provide routine label free quantitative information. In this report, the
      performance of the Hi3 label free method was assessed based on the analysis of a
      plasma-derived protein mixture. The following parameters of the method (CVs) were
      determined: repeatability 13.8%, intermediate precision 27.6%, bias 32.3% and
      linearity observed over 3 orders of magnitude. Finally an accuracy of 42.5%
      corresponding to a confidence interval within 2 fold the expected protein
      abundance should be a good approximation of the method performance.

PMID- 29572128
TI  - A simple and reproducible protocol of glass surface silanization for TIRF
      microscopy imaging.
AB  - We describe a simple and reproducible protocol for the preparation of microscope
      glass slides for in vitro motility assays that use total internal reflection
      fluorescence microscopy. The developed method utilizes trimethylchlorosilane
      (TMCS) as a silanizing reagent, which in the presence of imidazole as a catalyst
      and under optimized conditions enables reproducible preparation of high-quality
      hydrophobic glass surfaces. This method presents a simplification and improvement
      in reproducibility over the commonly applied protocol utilizing
      dichlorodimethylsilane (DDS) as a silanizing agent. We demonstrate the
      applicability of the new method by performing the analysis of the interactions of
      a molecular motor, kinesin-1 with microtubules.

PMID- 29572130
TI  - "I was really sceptical...But it worked really well": a qualitative study of
      patient perceptions of telephone-delivered exercise therapy by physiotherapists
      for people with knee osteoarthritis.
AB  - OBJECTIVE: Physiotherapists typically prescribe exercise therapy for people with
      osteoarthritis (OA) via face-to-face consultations. This study aimed to explore
      peoples' perceptions of exercise therapy delivered by physiotherapists via
      telephone for their knee OA. DESIGN: A qualitative study (based on interpretivist
      methodology) embedded within a randomised controlled trial. Semi-structured
      individual interviews were conducted with 20 people with knee OA who had received
      exercise advice and support from one of eight physiotherapists via telephone over
      6 months. Interviews were audio recorded, transcribed verbatim and thematically
      analysed. RESULTS: Although people with OA were initially sceptical about
      receiving exercise therapy via telephone, they described mostly positive
      experiences, valuing the convenience and accessibility. However, some desired
      visual contact with the physiotherapist and suggested including video
      conferencing calls or an initial in-person clinic visit. Participants valued the
      sense of undivided focus and attention they received from the physiotherapist and
      believed that they were able to communicate effectively via telephone.
      Participants felt confident performing their exercise program without supervision
      and described benefits including increased muscular strength, improved pain, and
      ability to perform tasks that they had not been previously able to. CONCLUSIONS:
      People with knee OA held mostly positive perceptions about receiving exercise
      therapy from a physiotherapist via telephone, suggesting that such a service is
      broadly acceptable to consumers. Such services were generally not viewed as a
      substitute for face-to-face physiotherapy care, but rather as a new option that
      could increase accessibility of physiotherapy services, particularly for follow
      up consultations.

PMID- 29572129
TI  - Subchondral trabecular bone integrity changes following ACL injury and
      reconstruction: a cohort study with a nested, matched case-control analysis.
AB  - OBJECTIVE: There is limited information regarding changes in bone architecture
      following anterior cruciate ligament (ACL) injury. The objective of this study
      was to evaluate differences in tibial fractal signature in the medial and lateral
      compartments following ACL injury and describe how these values change following
      ACL-reconstruction and return to activity. DESIGN: This was a prospective cohort
      study with a nested case-control analysis. ACL-injured subjects and matched
      controls were evaluated at pre-surgical baseline and post ACL reconstruction
      follow-up at a mean of 46 months. Serial Fractal Dimensions (FD) of tibial
      subchondral bone architecture were calculated in medial and lateral regions of
      interest in the horizontal and vertical dimensions. RESULTS: In the medial and
      lateral compartments, there were significant differences in the vertical FD
      signature for ACL-injured subjects at final follow-up, when compared to the
      contralateral healthy tibia (medial P < 0.0001; lateral P < 0.0001) and the
      control group (medial P = 0.01; lateral P < 0.0001). Similarly, in the lateral
      compartment, there were significant differences in the horizontal FD profile for
      ACL-injured subjects at final follow-up, when compared to the contralateral
      healthy tibia (P = 0.003) and the controls (P < 0.0001). There were no
      significant side-to-side differences in FDs among healthy control subjects in the
      medial or lateral compartments at baseline or final follow-up. CONCLUSION: At 46
      month follow-up, FD profiles are significantly different, and show an overall
      lower FD signature, for ACL-injured knees when compared to the contralateral
      healthy knee and uninjured controls. Additionally, this study provided the first
      side-to-side symmetry data of medial and lateral FD values in healthy controls.

PMID- 29572131
TI  - Oxidative stress-mediated influence of plasma DPP4 activity to BDNF ratio on mild
      cognitive impairment in elderly type 2 diabetic patients: results from the GDMD
      study in China.
AB  - OBJECTIVE: Increased dipeptidyl peptidase-4 (DPP4) activity and reduced brain
      derived neurotrophic factor (BDNF) in peripheral circulation are both associated
      with a high risk of mild cognitive impairment (MCI) in the elderly. Hence, we
      aimed to investigate the association between plasma DPP4 activity to BDNF ratio
      (DBR) and MCI in elderly patients with type 2 diabetes. DESIGN AND METHODS: We
      measured plasma DPP4 activity, BDNF levels, oxidative stress parameters,
      inflammatory markers and calculated DBR in 1833 elderly type 2 diabetic patients
      aged 60 years or older. MCI was diagnosed according to the National Institute on
      Aging-Alzheimer's Association workgroups criteria. Further, mediation analysis
      was performed to estimate the mediator role of oxidative stress on the
      relationship between DPP4 activity and BDNF. RESULTS: DPP4 activity was
      negatively associated with BDNF (r = -0.408, P < 0.001). Oxidative stress,
      particularly in male participants, acted as a partial mediator in the
      relationship between DPP4 activity and BDNF. Participants in the highest quartile
      of DBR had higher nitrotyrosine, 8-isoPGF2a, interleukin-6, C-reactive protein
      and lower Montreal Cognitive Assessment score compared with those in the lowest
      quartile. The odds ratio (5.15, 95% CI 3.64-7.30) for MCI in the highest DBR
      quartile was significantly higher than in the lowest quartile. The risk for MCI
      increased with higher levels of DPP4 activity and lower levels of BDNF.
      CONCLUSIONS: Oxidative stress partially mediates the inverse relationship between
      DPP4 and BDNF. Our data provide evidence for a strong link between DBR and MCI,
      suggesting DBR to be a new biomarker for MCI in type 2 diabetic patients.

PMID- 29572132
TI  - Sleep biology updates: Hemodynamic and autonomic control in sleep disorders.
AB  - Sleep disorders like obstructive sleep apnea syndrome, periodic limb movements in
      sleep syndrome, insomnia and narcolepsy-cataplexy are all associated with an
      increased risk of cardiovascular diseases. These disorders share an impaired
      autonomic nervous system regulation that leads to increased cardiovascular
      sympathetic tone. This increased cardiovascular sympathetic tone is, in turn,
      likely to play a major role in the increased risk of cardiovascular disease.
      Different stimuli, such as intermittent hypoxia, sleep fragmentation, decrease in
      sleep duration, increased respiratory effort, and transient hypercapnia may all
      initiate the pathophysiological cascade leading to sympathetic overactivity and
      some or all of these are encountered in these different sleep disorders. In this
      manuscript, we outline the different pathways leading to sympathetic over
      activity in different sleep conditions. This augmented sympathetic tone is likely
      to play an important role in the development of cardiovascular disease in
      patients with sleep disorders, and it is further hypothesized to that
      sympathoexcitation contributes to the metabolic dysregulation associated with
      these sleep disorders.

PMID- 29572134
TI  - Replacement of the Distorted Dentition of the Cone-Beam Computed Tomography Scans
      for Orthognathic Surgery Planning.
AB  - PURPOSE: Cone-beam computed tomography (CBCT) does not record dental morphology
      accurately because of the scattering produced by metallic restorations and the
      reported magnification of the dentition. The aim of this study was the
      development and evaluation of a new method for the replacement of the distorted
      dentition of CBCT scans with a 3-dimensional (3D) dental image captured by a
      digital intraoral camera. MATERIALS AND METHODS: Six dried skulls with
      orthodontic brackets fixed on the teeth were used in this study. Three intraoral
      markers made of dental stone were constructed and attached to orthodontic
      brackets. The skulls were scanned by CBCT and the occlusal surfaces were captured
      using the TRIOS 3D intraoral scanner. The digital intraoral scan (IOS) was fused
      into the CBCT models. This produced a new composite digital model of the skull
      and the dentition. The skulls were scanned again using the commercially accurate
      Faro laser arm to produce the 3D model the skull and teeth gold standard for the
      assessment of the accuracy of the developed method. This was assessed by
      measuring the distance between the occlusal surfaces of the new composite model
      and the gold standard 3D laser produced model. RESULTS: The results showed the
      errors related to the superimposition of the intraoral image on the CBCT to
      replace the distorted dentition were 0.11 to 0.20 mm. CONCLUSION: The results of
      this novel method suggest that the dentition on the CBCT scan can be accurately
      replaced with the digital IOS image captured by an intraoral scanner to create a
      composite model that will improve the accuracy of digital orthognathic surgical
      planning and the fabrication of the guiding occlusal wafer.

PMID- 29572133
TI  - Effect of Obesity or Metabolic Syndrome and Diabetes on Osseointegration of
      Dental Implants in a Miniature Swine Model: A Pilot Study.
AB  - PURPOSE: The increasing prevalence of obesity or metabolic syndrome (O/MS) and
      type 2 diabetes mellitus (DM) remains a global health concern. Clinically
      relevant and practical translational models mimicking human characteristics of
      these conditions are lacking. This study aimed to demonstrate proof of concept of
      the induction of stable O/MS and type 2 DM in a Gottingen minipig model and
      validate both of these disease-adjusted Gottingen minipig models as impaired
      healing models for the testing of dental implants. MATERIALS AND METHODS: Nine
      minipigs were split into 3 groups-control (normal diet), obese (cafeteria diet),
      and diabetic (cafeteria diet plus low-dosage streptozotocin)-followed by
      placement of dental implants. Inflammatory markers including tumor necrosis
      factor alpha, C-reactive protein, and cortisol were recorded for each study
      group. Removal torque was measured, and histomorphometric analysis (bone-to
      implant contact and bone area fraction occupancy) was performed. RESULTS: O/MS
      pigs showed, on average, a 2-fold increase in plasma C-reactive protein (P < .05)
      and cortisol (P < .09) concentrations compared with controls; DM pigs showed, on
      average approximately, a 40-fold increase in plasma tumor necrosis factor alpha
      levels (P < .05) and a 2-fold increase in cortisol concentrations (P < .05)
      compared with controls. The impact of O/MS and DM on implants was determined. The
      torque to interface failure was highest in the control group (200 N-cm) and
      significantly lower in the O/MS (90 N-cm) and DM (60 N-cm) groups (P < .01). Bone
      formation around implants was significantly greater in the control group than in
      the O/MS and DM groups (P < .02). CONCLUSIONS: Both O/MS and DM minipigs express
      a human-like disease phenotype, and both presented bone-healing impairment around
      dental implants. Our finding of no significant difference between type 2 DM and
      O/MS in bone formation around implants provides evidence that further
      investigation of the impact of O/MS is warranted.

PMID- 29572135
TI  - First characterization of an anti-lipopolysaccharide factor (ALF) from
      hydrothermal vent shrimp: Insights into the immune function of deep-sea
      crustacean ALF.
AB  - Anti-lipopolysaccharide factor (ALF) is a type of antimicrobial peptides (AMPs)
      with a vital role in antimicrobial defense. Although a large amount of ALFs have
      been identified from neritic and fresh water crustacean species, no functional
      investigation of ALFs from deep-sea animals have been documented. In the present
      study, we characterized the immune function of an ALF molecule (named RspALF1)
      from the shrimp Rimicaris sp. residing in the deep-sea hydrothermal vent in
      Desmos, Manus Basin. RspALF1 shares 51.5%-62.4% overall sequence identities with
      known shrimp ALFs and contains the conserved LPS binding domain (LBD). Both
      recombinant RspALF1 (rRspALF1) and the LBD-derived peptide (ALF1P1) bound to the
      cell wall components of Gram-negative and Gram-positive bacteria and killed a
      wide range of bacteria, especially those from deep-sea hydrothermal field, by
      damaging bacterial cellular structures. The bactericidal activities of rRspALF1
      and ALF1P1 were optimal and stably maintained from 4  degrees C to 37  degrees C,
      which is comparable to the ambient temperature range of the habitat of Rimicaris
      sp. In addition to bacteria, rRspALF1 and ALF1P1 also exhibited anti-fungal
      activity. rRspALF1 and ALF1P1 exhibited high killing efficiencies, which, in
      terms of MIC values, were ranged between 0.25 MUM and 4 MUM for bacteria and 4
      MUM-8 MUM for fungi. When introduced in vivo, both rRspALF1 and ALF1P1
      effectively inhibited bacterial infection in shrimp and reduced the dissemination
      of bacterial and viral pathogens in fish. Together, these results provide the
      first insight into the biological property of deep-sea ALF and indicate that
      RspALF1 very likely plays a significant role in immune defense by functioning as
      a highly effective antimicrobial with a broad target range.

PMID- 29572136
TI  - Addressing Racial Disparity in Colorectal Cancer Screening With CT Colonography:
      Experience in an African-American Cohort.
AB  - BACKGROUND: Incidence and mortality from colorectal cancer (CRC) are higher among
      African Americans where CRC screening rates lag behind non-Hispanic whites. The
      purpose of this investigation was to evaluate CT colonography (CTC) performance
      and outcome measures in an African-American cohort. MATERIALS AND METHODS: This
      study is an institutional review board-approved and Health Insurance Portability
      and Accountability Act-compliant study. Retrospective evaluation of the African
      American cohort from the Atlanta VA Medical Center (Decatur, Georgia) CTC
      screening program. Colonoscopy referral rates and histologic diagnoses were
      evaluated. RESULTS: CTC studies (n = 2490; mean age, 59.5 years [range, 50-80
      years]; 85.5% male; all African American) were performed between 2007 and 2016.
      The per-patient CTC positive rate was 9.8% for polyps from 6 to 9 mm, 5.4% for
      polyps from 10 to 29 mm, and 1.3% for masses >= 30 mm. Based on CTC findings and
      patient preference, 13.9% of patients were referred to optical colonoscopy and
      2.9% were referred to CTC follow-up. Of patients recommended to undergo
      colonoscopy, 80.6% completed the procedure and colonic pathology was confirmed in
      83.2% thereof. Histologic diagnoses were 221 tubular adenomas (161 6-9 mm; 60 >=
      10 mm), 59 tubulovillous adenomas/villous adenomas (14 6-9 mm; 45 >= 10 mm), 34
      hyperplastic-serrated polyps (27 6-9 mm; 7 >= 10 mm), 18 adenocarcinomas (all >=
      10 mm), and 11 adenomas with high-grade dysplasia (all >= 10 mm). The per-patient
      positivity rate for patients who had optical colonoscopy (n = 279) was 71.3% for
      adenoma, 9.7% for hyperplastic polyp, and 6.1% for adenocarcinoma. CONCLUSIONS:
      CTC is an effective screening modality for African-American adults and could
      potentially improve rates of colorectal screening in this underserved population.

PMID- 29572138
TI  - Preparation, characterization, digestibility and antioxidant activity of
      quercetin grafted Cynanchum auriculatum starch.
AB  - In this study, a novel method was developed to conjugate quercetin with Cynanchum
      auriculatum starch. Quercetin was first succinylized and then grafted onto C.
      auriculatum starch through a N,N'-carbonyldiimidazole mediated reaction. The
      obtained water soluble quercetin grafted starch (quercetin-g-starch) was
      characterized by several instrumental methods. UV-vis spectrum of quercetin-g
      starch aqueous solution exhibited two absorption bands at around 300 and 430nm.
      Fourier-transform infrared spectrum of quercetin-g-starch showed characteristic
      bands at 1731 and 1568cm-1, assigning to CO stretching of esterified carboxyl
      group and CC stretching of aromatic ring, respectively. Proton nuclear magnetic
      resonance spectrum of quercetin-g-starch showed partial proton signals of starch
      (3.30-5.47ppm) and quercetin (6.19-7.68ppm). All above results suggested
      quercetin was successfully grafted onto C. auriculatum starch. Besides, quercetin
      g-starch particles were irregular in shape and were in an amorphous state.
      Notably, the thermal stability, resistant starch content as well as antioxidant
      activity of C. auriculatum starch was greatly enhanced by grafting with
      quercetin. This indicated the potential of quercetin-g-starch in the development
      of a novel resistant starch with antioxidant activity.

PMID- 29572137
TI  - Probing the interaction interface of the GADD45beta/MKK7 and MKK7/DTP3 complexes
      by chemical cross-linking mass spectrometry.
AB  - GADD45beta is selectively and constitutively expressed in Multiple Myeloma cells,
      and this expression correlates with an unfavourable clinical outcome. GADD45beta
      physically interacts with the JNK kinase, MKK7, inhibiting its activity to enable
      the survival of cancer cells. DTP3 is a small peptide inhibitor of the
      GADD45beta/MKK7 complex and is able to restore MKK7/JNK activation, thereby
      promoting selective cell death of GADD45beta-overexpressing cancer cells.
      Enzymatic MS foot-printing and diazirine-based chemical cross-linking MS (CX-MS)
      strategies were applied to study the interactions between GADD45beta and MKK7
      kinase domain (MKK7_KD) and between DTP3 and MKK7_KD. Our data show that the
      binding between GADD45beta and MKK7 largely occurs between GADD45beta loop 2
      (region 103-117) and the kinase enzymatic pocket. We also show that DTP3
      interferes with this GADD45beta/MKK7 interaction by contacting the MKK7 peptides,
      113-136 and 259-274. Accordingly, an MKK7_KD Delta(101-136) variant lacking
      Trp135 did not produce a fluorescence quenching effect upon the binding of DTP3.
      The assessment of the interaction between GADD45beta and MKK7 and the elucidation
      of the recognition surfaces between DTP3 and MKK7 significantly advance the
      understanding of the mechanism underlying the inhibition of the GADD45beta/MKK7
      interaction by DTP3 and pave the way to the design of small-molecule DTP3
      analogues.

PMID- 29572139
TI  - Hepatoprotective effects exerted by Poria Cocos polysaccharides against
      acetaminophen-induced liver injury in mice.
AB  - Our study was to investigate the potential pharmacological activity of Poria
      Cocos polysaccharides (PCP) against acetaminophen (APAP)-induced liver injury in
      mice. PCP-dosed mice were used to conducting biochemical assays of serological
      liver enzyme (ALT), lactate dehydrogenase (LD), inflammatory cytokines (TNF
      alpha, IL-6), and immunoassays for functional proteins in the livers.
      Consequently, APAP-exposed mice resulted in elevated levels of ALT, LD, TNF
      alpha, IL-6 in sera. Interestingly, PCP-dosed mice exhibited reduced ALT, LD and
      inflammatory cytokines in blood. Inflammatory infiltration and cell death in
      liver tissue were decreased following by PCP treatments. Furthermore,
      immunofluorescence staining showed that AKR7A, c-Jun, Bcl-2-positive cells were
      increased in PCP-dosed livers in mice, while Bax-labeled cells were decreased. In
      addition, hepatocellular down-regulated NF-kappaBp65, IkBalpha expressions were
      observed dose-dependently in PCP-dosed livers in mice. Taken together, the
      current findings indicate that Poria Cocos polysaccharides exert pharmacological
      bioeffects against APAP-induced liver injury in mice, and the underlying
      molecular mechanism is associated to suppressing inflammatory response and
      apoptosis in liver cells.

PMID- 29572140
TI  - Preparation, characterization and in vivo antidiabetic effects of polysaccharides
      from Pachyrrhizus erosus.
AB  - Polysaccharides were extracted from Pachyrrhizus erosus (PEP) and three fractions
      (PEP60, PEP80 and PEP95) were separated by ethanol precipitation. Antidiabetic
      activities of three fractions were evaluated by streptozotocin-induced diabetic
      mouse model. Three PEP fractions reduced fasting blood glucose levels in mice,
      and regulated the levels of glycated serum protein, total triglyceride and total
      cholesterol in serum. In liver, the levels of glycogen content, glutathione
      peroxidase and superoxide dismutase activities and lipid peroxidation were
      recovered by PEP fractions. The histological analysis indicated that PEP
      fractions could protect the tissue structures of pancreas, liver and kidney from
      diabetic damages. In kidney, PEP fractions decreased the mesangial matrix index
      and inhibited the expression of transforming growth factor-beta1. PEP95 showed
      stronger antidiabetic activity than PEP60 and PEP80. PEP95-DS was separated from
      PEP95 by DEAE-cellulose and Sephadex G-100 column chromatography. The chemical
      characteristics of PEP95-DS were evaluated. The average molecular weight of PEP95
      DS was 11.4kDa, and it was composed of mannose: rhamnose: glucosamine: glucose:
      galactose: xylose: arabinose was 5.4:1.7:8.5:160.7:11.8:1:2.7. Furthermore, the
      spectral characteristics of PEP95-DS were analyzed. Our results indicated PEP
      could be used as a function ingredient in foods to prevent oxidation and
      diabetes.

PMID- 29572141
TI  - Hydrogel matrices based on elastin and alginate for tissue engineering
      applications.
AB  - Hydrogels from natural polymers are widely used in tissue engineering due to
      their unique properties, especially when regarding the cell environment and their
      morphological similarity to the extracellular matrix (ECM) of native tissues. In
      this study, we describe the production and characterization of novel hybrid
      hydrogels composed of alginate blended with elastin from bovine neck ligament.
      The properties of elastin as a component of the native ECM were combined with the
      excellent chemical and mechanical stability as well as biocompatibility of
      alginate to produce two hybrid hydrogels geometries, namely 2D films obtained
      using sonication treatment and 3D microcapsules produced by pressure-driven
      extrusion. The resulting blend hydrogels were submitted to an extensive physico
      chemical characterization. Furthermore, the biological compatibility of these
      materials was assessed using normal human dermal fibroblasts, indicating the
      suitability of this blend for soft tissue engineering.

PMID- 29572142
TI  - Rheological characterizations of concentrated binary gum mixtures with xanthan
      gum and galactomannans.
AB  - The steady and dynamic shear rheological properties of binary gum mixtures with
      xanthan gum (XG) and galactomannans (guar gum (GG) and locust bean gum (LBG))
      were examined in a concentrated solution (1% w/w) as a function of gum mixing
      ratio (100/0, 75/25, 50/50, and 0/100). All samples, except for individual GG and
      LBG, showed high shear-thinning behavior with yield stress. The values of flow
      (K, etaa,50, and sigmaoc) and dynamic rheological parameters (G' and G") of XG-GG
      and XG-LBG mixtures were significantly higher compared to XG alone, indicating
      that the flow and viscoelastic properties of binary gum mixtures were greatly
      affected by the addition of GG and LBG. The maximum elasticity synergistic
      interaction for XG-galactomannans mixtures was observed at a mixing ratio of
      50/50, showing a greatly positive deviation between measured and calculated
      values of G'. These results suggest that the synergistic effect of GG and LBG
      addition on rheological properties of XG appears to be due to intermolecular
      interaction occurred between XG and galactomannans, as confirmed by dynamic
      rheological properties.

PMID- 29572143
TI  - Guar gum-crosslinked-Soya lecithin nanohydrogel sheets as effective adsorbent for
      the removal of thiophanate methyl fungicide.
AB  - Rapid increase in use of fungicides for the agricultural and industrial purposes
      has marked the deterioration of water resources which ultimately affects the
      human life. Accordingly, various attempts have been made in the removal of these
      noxious compounds. In the same context, we are presenting biopolymers based
      nanohydrogel sheets; guar gum-crosslinked-Soya lecithin nanohydrogel sheets (GG
      crosslinked-SY NHS) used for the effective removal of a fungicide; thiophanate
      methyl from aqueous solution. Guar gum and soya lecithin were employed as the
      biopolymers in the fabrication of nanohydrogel sheets due to their non- toxic
      nature, easy availability, cheapness and significant properties. Due to the
      presence of highly reactive functional groups onto the surface of GG-crosslinked
      SY NHS, good adsorption results have been obtained. Maximum adsorption capacity
      of 59.205mg/g was observed with 20mg GG-crosslinked-SY NHS and 25ppm thiophanate
      methyl solution concentration as calculated from the Langmuir isotherm. Results
      showed that neutral pH favoured the adsorption process. Kinetics results were
      indicative of the physical interactions between the thiophanate methyl and GG
      crosslinked-SY NHS surface. Thermodynamic results have shown the spontaneous and
      endothermic adsorption process.

PMID- 29572144
TI  - Locust bean gum galactomannan hydrolyzed by thermostable beta-d-mannanase may
      reduce the secretion of pro-inflammatory factors and the release of granule
      constituents.
AB  - Locust bean gum (LBG) galactomannan has been claimed to have applications in the
      biopharmaceutical field. However, the effects of LBG galactomannan on
      immunomodulatory aspects are not yet clear. The purpose of this study was to over
      express thermostable beta-d-mannanase from the thermophilic actinomycete
      Thermobifida fusca BCRC 19214 using a Pichia pastoris expression system. The
      maximum intracellular beta-d-mannanase activity obtained from the cell-free
      extract was approximately 40.0U/mL after 72h of cultivating a P. pastoris
      transformant (pPICZ-man) induced with methanol. Hydrolysis of native LBG
      galactomannan with 8U/mL beta-d-mannanase for 24h significantly decreased the
      weight-average molecular weight of LBG galactomannan from 5,580,010 to 3188.
      Native and hydrolyzed LBG galactomannan in a range of 0-0.2% did not trigger
      significant cytotoxicity after 24h of treatment compared with the control. The
      native LBG galactomannan stimulated RAW 264.7 cells to produce cytokine TNF-alpha
      dose-dependently, but there was no significant IL-1beta or nitric oxide
      production. The native LBG galactomannan also stimulated beta-hexosaminidase
      secretion in RBL-2H3 cells. After the native LBG galactomannan was hydrolyzed
      with beta-d-mannanase, all of the immunological properties disappeared. These
      results suggest the possible immunomodulatory effects of native LBG
      galactomannan.

PMID- 29572145
TI  - Fabrication of asymmetric nanostarch reinforced Chitosan/PVP membrane and its
      evaluation as an antibacterial patch for in vivo wound healing application.
AB  - Starch is an abundant, relatively inexpensive and ecofriendly materials which can
      be easily convert into nanoparticle and also as filler for the preparation of
      bionanocomposite for wound dressing application. Symmetric and asymmetric
      Chitosan(C)/PVP(P) films containing porous structure supported with nanostarch
      (NS) were prepared by salt leaching method for wound dressing application.
      Symmetric Chitosan/PVP/Nanostarch (CPNS) film with 1% and 3% wt nanostarch was
      prepared without coating of stearic acid whereas asymmetric
      Chitosan/PVP/Nanostarch-Stearic acid (CPNS-S) film was prepared by coating of
      stearic acid. The stearic acid coated surface possesses hydrophobic water
      repellent, microporous, bacterial anti adhesion property and the stearic acid
      uncoated hydrophilic surface shows superior antibacterial and noncytotoxicity
      property with highly porous character. All the symmetric and asymmetric films
      exhibit almost same mechanical, barrier, swelling and hemolytic property reveals
      that the stearic acid does not affect the physical and hemolytic property whereas
      the concentration of nanostarch greatly influence the above property. The
      reinforcement of nanostarch with chitosan and PVP was proved by TEM and SEM
      analysis. The CPNS1%-S film shows excellent S. aureus anti adhesion property.
      Furthermore, the in vivo excision-type wound healing proved that the CPNS1%-S
      film enhanced the healing effect and increased re-epithelialization and collagen
      formation.

PMID- 29572146
TI  - Catalytic characteristics and application of l-asparaginase immobilized on
      aluminum oxide pellets.
AB  - l-asparaginase from Escherichia coli (l-ASNase) was covalently immobilized on
      aluminum oxide pellets (AlOPs) using a cross-linking agent, glutaraldehyde.
      Maximum immobilization yield (85.0%) was obtained after optimizing immobilization
      parameters using response surface methodology (RSM). Both free and immobilized l
      ASNase (AlOP-ASNase) were optimally active at 37 degrees C and pH7.5. However,
      the bioconjugate exhibited enhanced activity and stability at different pH and
      temperatures. It had higher affinity (low Km) and was comparatively more stable
      in presence of some solvents (ethyl acetate, acetone, acetonitrile), metal ions
      (Ag+, Zn2+) and beta-mercaptoethanol. AlOP-ASNase was reused in a glass column
      reactor for l-asparagine hydrolysis upto nine successive cycles without any loss
      in activity. The AlOP-ASNase was effective in lowering l-asparagine level in
      blanched potato chips indicating its potential use in mitigating acrylamide
      formation in starchy foods. This cost-effective enzyme preparation had shelf-life
      of more than 30days and can be effectively used in starch based food industries.

PMID- 29572147
TI  - Chloroquine diphosphate bearing dextran nanoparticles augmented drug delivery and
      overwhelmed drug resistance in Plasmodium falciparum parasites.
AB  - Chloroquine diphosphate (CHQ) is primarily used for the treatment of Plasmodium
      falciparum malaria at the dose of 500mg orally or 10mg/kg parenterally. However,
      point mutations in Plasmodiumfalciparum chloroquine resistance transporter
      (PfCRT) protein and Plasmodium falciparum multidrug resistance protein 1 (Pfmdr1)
      localized in digestive vacuole membrane, are responsible for CHQ resistance.
      Therefore, in present investigation, dextran nanoparticles bearing chloroquine
      diphosphate (CHQ-DEX-NPs) were formulated by solvent diffusion method of size
      below 70nm with zeta-potential of -20.1+/-3.2mV. FT-IR, DSC and PXRD techniques
      confirmed the successful loading of drug in nanomatrix system with amorphous
      attributes. In vitro drug release analysis indicated the Higuchi pattern with
      diffusion controlled drug release. The IC50 of CHQ-DEX-NPs in sensitive (3D7) and
      resistant (RKL9) Plasmodium falciparum strains was estimated to be 0.031-MUg/ml
      and 0.13-MUg/ml significantly lower than 0.059-MUg/ml and 0.36-MUg/ml of CHQ. The
      augmented therapeutic efficacy of CHQ-DEX-NPs may be credited to deposition of
      tailored nanoparticles in food vacuoles of malaria parasites owing to the
      affinity of parasite towards DEX that consequently lower the drug resistance and
      improved the therapeutic index. In conclusion, CHQ-DEX-NPs must be evaluated
      under a set of stringent in vivo parameters to establish its therapeutic efficacy
      in preclinical model.

PMID- 29572148
TI  - Preparation and characterization of novel magnetic Fe3O4/chitosan/Al(OH)3 beads
      and its adsorption for fluoride.
AB  - A novel magnetic bioadsorbent beads composed of Fe3O4, chitosan, and Al(OH)3
      (Fe3O4/CS/Al(OH)3) was synthesized by a modified solvothermal and in-situ
      reaction. The composite adsorbent was characterized by Fourier-transform infrared
      spectroscopy, X-ray diffraction, scanning electron microscopy, energy dispersive
      X-ray spectroscopy, and vibrating sample magnetometer, respectively. Adsorption
      toward F- onto Fe3O4/CS/Al(OH)3 was investigated as a function of Fe3O4
      concentration, initial solution pH, adsorbent dosage, initial fluorion
      concentration, co-existing ions in water and initial temperature. The addition of
      Fe3O4 could enhance the adsorption properties of CS/Al(OH)3. The saturated
      adsorption capacity of magnetic Fe3O4/CS/Al(OH)3 calculated from the Langmuir
      isotherm model was 76.63mg/g at 298K. The adsorption isotherm of F- followed
      Langmuir isotherm model and the adsorption kinetics fitted better to the pseudo
      second order kinetic model. The influence of temperature confirmed that the
      adsorption was spontaneous and endothermic. The magnetic Fe3O4/CS/Al(OH)3 beads
      could be easily separated from water under a low magnetic field.

PMID- 29572149
TI  - Polyguluronate sulfate (PGS) attenuates immunological liver injury in vitro and
      in vivo.
AB  - Hepatocyte damage, especially immunological liver injury, is a key process in the
      pathogenesis of hepatitis virus-induced liver diseases. The aim of this study was
      to investigate the protective effects of polyguluronate sulfate (PGS) against
      immunological liver damage. The results showed that PGS significantly reduced the
      H2O2-induced oxidative stress and increased the cell viability in HepG2
      hepatocytes. PGS also suppressed the production of malondialdehyde (MDA), lactate
      dehydrogenase (LDH), TNF-alpha, and IL-6, while up-regulating the activity of SOD
      in HepG2 cells. Further, PGS (150 and 300mg/kg/day) significantly attenuated the
      elevation of serum glutamate pyruvate transaminase (ALT), aspartate
      aminotransferase (AST), total bilirubin (TBiL), in addition to liver MDA and NO
      levels in Con A-induced immunological liver injury within mice (P<0.05).
      Significant improvements of organ indexes (liver, spleen, and thymus) were
      observed in PGS-treated mice. PGS also significantly reduced the disorganization
      of hepatocytes and decreased the inflammatory cell infiltration caused by Con A
      treatment, suggesting that PGS was able to attenuate Con A-induced liver injury.
      In conclusion, PGS possesses significant hepatoprotective effects on
      immunological liver injury in vitro and in vivo, and this may be related to its
      antioxidant activities.

PMID- 29572150
TI  - Molecular dynamic of curcumin/chitosan interaction using a computational
      molecular approach: Emphasis on biofilm reduction.
AB  - Nanotechnology-based drug delivery systems have been used to enhance
      bioavailability and biological activities. Chitosan incorporating curcumin can
      serve as a biocompatible substitute for metallic nanoparticles in preventing
      biofilm formation of Streptococcus mutans and plaque on teeth. The interactions
      between chitosan nanoparticle as a carrier and curcumin, a natural antibacterial
      agent, were simulated. The binding conformation between curcumin-chitosan was
      obtained using the Lamarckian Genetic Algorithm in AutodockTM software in
      chitosan nanoparticle. The interaction stability was examined in the molecular
      dynamic stages, with isothermal-isobaric ensemble in the CHARMM Force Field. The
      results showed the root mean square deviation (RMSD) and the root mean square
      fluctuations (RMSF) for all complex's atoms were relaxed after 4ns (RMSD for the
      all-atoms was 26.81+/-0.1 (A); RMSF 1.13+/-0.02A). For each section, the
      estimation of RMSD, RMSF, radius of gyration, inter-H bond and other analysis
      confirmed that, during the first interval;10ns, there was a stable binding
      between the two sections. Although all bindings disappeared from 10 to 20ns, the
      curcumin was trapped inside the chitosan nanoparticles, and no release took place
      until 20ns, after which the curcumin began to release. This trend suggests that
      chitosan nanoparticle has ability to carry the curcumin.

PMID- 29572151
TI  - Fire resistant behaviour of cellulosic textile functionalized with wastage plant
      bio-molecules: A comparative scientific report.
AB  - Three different wastage plant based bio-molecules named banana peel powder (Musa
      acuminata) (BPP), coconut shell (Cocos nucifera) extract (CSE) and pomegranate
      rind (Punica granatum) extract (PRE) have been explored as fire resistant
      material on the cellulosic polymer (cotton fabric). To this end, extracts have
      been applied to the cotton fabric in different concentration at elevated
      temperature for specific time period. Treated cotton fabric showed 6 (BPP), 8.5
      (CSE) and 12 (PRE) times lower vertical burning rate compared to the control
      cotton fabric. Thermo-gravimetry (TG) curves and the limiting oxygen index (LOI)
      value revealed that the PRE extract (LOI: 32) treated fabric encompassed more
      thermal stability compared to the BPP (LOI:26) and the CSE (LOI: 27) treated
      fabric as it showed higher oxygen index and more weight retention (40%) at higher
      temperature 450 degrees C. Moreover, the carbonaceous samples remained after the
      burning of the extracts and the treated fabrics showed structural integration and
      more carbon content [65.6 (PRE extract) and 76.3% (PRE treated cotton)] compared
      to the fragile, net like char of the control cotton fabric, having less carbon
      content (49.8%). Gas Chromatography Mass spectroscopy (GC-MS) of the different
      extracts (CSE, PRE, BPP) used for the study showed the presence of high molecular
      weight aromatic phenolic compounds, tannin based compound and the nitrogen
      containing alkaloids, responsible for fire resistant effect of the different
      extract treated fabric. Besides fire retardancy, all the treated fabric showed
      attractive natural colour (measured by colour strength values) and there has been
      no adverse effect on the tensile strength property of the fabric after the
      treatment.

PMID- 29572152
TI  - Erratum to "Brenner, T., & Matsukawa, S. (2016). Anomalous diffusion of
      poly(ethylene oxide) in agarose gels" [Int. J. Biol. Macromolecules, 92, 1151
      1154].

PMID- 29572153
TI  - Amphiphilic polymeric micelles originating from 1,4-beta-D-glucan-g-polyphenylene
      oxide as the carriers for delivery of docetaxel and the corresponding release
      behaviors.
AB  - A novel amphiphilic polymeric drug carrier was synthesized through grafting
      polymerization of water-soluble 1,4-beta-D-glucan from cotton cellulose tailored
      and polypropylene oxide (PPO), and then use thereof to synthesize graft copolymer
      1,4-beta-D-glucan-PPO-docetaxel (DTX). The products were characterized by FTIR,
      1H NMR, and 13C NMR. The physicochemical characteristics of 1,4-beta-D-glucan-PPO
      and 1,4-beta-D-glucan-PPO-DTX such as molecular weight distribution (MWD), micro
      morphology, size, critical micelle concentration (CMC), aggregation number of
      micelle (N), in vitro stability and drug pharmacokinetic study in vivo were
      investigated. The results reveal that the degree of polymerization (DP) of the
      water-soluble 1,4-beta-D-glucan from cotton cellulose tailored is equal to 7; the
      1,4-beta-D-glucan-PPO surfactant possesses good surface activity while the adduct
      number of propylene oxide reaches appropriately to 20; the DTX is completely
      dispersed in water medium with 1,4-beta-D-glucan-PPO-DTX micelle and the drug
      conjugated percent is up to 40.3%; In vitro study confirms that 1,4-beta-D-glucan
      PPO-DTX has the capacity for sustained drug release; In plasma, 1,4-beta-D-glucan
      PPO-DTX exhibits a significantly enhanced Cmax, AUC(0-t) and T1/2 compared with
      DTX. These results demonstrate that 1,4-beta-D-glucan-PPO has the potential to be
      used as a novel biocompatible biomaterial for drug delivery.

PMID- 29572154
TI  - Mechanistic understanding of the phase behavior of supersaturated solutions of
      poorly water-soluble drugs.
AB  - Amorphous solid dispersions (ASDs) are a promising formulation strategy to
      increase both the apparent aqueous solubility and bioavailability of poorly water
      soluble drugs. Upon dissolution under nonsink conditions, ASDs can generate
      highly supersaturated drug solutions which can undergo liquid-liquid phase
      separation (LLPS) and/or crystallization. In this study, the phase behavior of
      supersaturated solutions generated by antisolvent addition and upon the
      dissolution of ASDs was evaluated using fluorescence lifetime measurements and
      several other orthogonal techniques, including steady-state fluorescence
      spectroscopy, ultraviolet (UV) extinction and concentration profiles,
      ultracentrifuge measurements and nanoparticle tracking analysis. Ritonavir and
      lopinavir were chosen as poorly water-soluble model drugs, and the polymer,
      Kollidon VA64, was selected to form the dispersions. The fluorescence lifetime of
      the environment-sensitive fluoroprobe, PRODAN, was monitored to determine the
      occurrence of LLPS and crystallization. It was found that only the 10% w/w drug
      loading ASDs dissolved to a concentration in solution higher than the LLPS
      concentration and this led to an increase in the lifetime of PRODAN due to
      partitioning of the fluoroprobe into the drug-rich phase. In contrast, the 50%
      w/w drug loading ASDs did not reach the amorphous solubility, pointing to a
      dissolution behavior controlled by the low water solubility and high
      hydrophobicity of the drug. Fluorescence lifetime measurements were demonstrated
      to be extremely useful for the characterization of the phase behavior of
      supersaturated solutions of poorly water-soluble drugs.

PMID- 29572155
TI  - N-Terminomics identifies HtrA1 cleavage of thrombospondin-1 with generation of a
      proangiogenic fragment in the polarized retinal pigment epithelial cell model of
      age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of irreversible
      blindness in the elderly population. Variants in the HTRA1-ARMS2 locus have been
      linked to increased AMD risk. In the present study we investigated the impact of
      elevated HtrA1 levels on the retina pigment epithelial (RPE) secretome using a
      polarized culture system. Upregulation of HtrA1 alters the abundance of key
      proteins involved in angiogenesis and extracellular matrix remodeling.
      Thrombospondin-1, an angiogenesis modulator, was identified as a substrate for
      HtrA1 using terminal amine isotope labeling of substrates in conjunction with
      HtrA1 specificity profiling. HtrA1 cleavage of thrombospondin-1 was further
      corroborated by in vitro cleavage assays and targeted proteomics together with
      small molecule inhibition of HtrA1. While thrombospondin-1 is anti-angiogenic,
      the proteolytically released N-terminal fragment promotes the formation of tube
      like structure by endothelial cells. Taken together, our findings suggest a
      mechanism by which increased levels of HtrA1 may contribute to AMD pathogenesis.
      The proteomic data has been deposited to the ProteomeXchange Consortium via the
      PRIDE partner repository with the data set identifier. For quantitative secretome
      analysis, project accession: PXD007691, username: reviewer45093@ebi.ac.uk,
      password: 1FUpS6Yq. For TAILS analysis, project accession: PXD007139, username:
      reviewer76731@ebi.ac.uk, password: sNbMp7xK.

PMID- 29572156
TI  - The WNT signaling pathways in wound healing and fibrosis.
AB  - The WNT signaling pathways are major regulators of organ development. Ample
      research over the past few decades revealed that these pathways are critically
      involved in adult tissue homeostasis and stem cell function as well as the
      development of chronic diseases, such as cancer and fibrosis. In this review, we
      will describe the different WNT signal pathways, summarize the current evidence
      of WNT signal involvement in wound healing and fibrosis, and highlight potential
      novel therapeutic options for fibrotic disorders targeting WNT signaling
      pathways.

PMID- 29572157
TI  - Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal
      Masses?
AB  - PURPOSE: We characterize and apply the modified Bosniak classification system to
      a cohort of children with cystic renal lesions and known surgical pathology.
      MATERIALS AND METHODS: We identified all patients at our institution with cystic
      renal masses who also underwent surgery for these lesions. Patients without
      available preoperative imaging or pathology were excluded. All radiological
      imaging was independently reviewed by a pediatric radiologist blinded to
      pathological findings. Imaging characteristics (size, border, septations,
      calcifications, solid components, vascularity) were recorded from the most recent
      preoperative ultrasounds and computerized tomograms. The modified Bosniak
      classification system was applied to these scans and then correlated with final
      pathology. RESULTS: A total of 22 patients met study criteria. Median age at
      surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%)
      underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%)
      laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%)
      laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%),
      intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were
      modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and
      8 of 9 benign lesions (89%) were modified class 1 or 2. CONCLUSIONS: Cystic renal
      lesions in children with a modified Bosniak class of 1 or 2 were most often
      benign, while class 3 or 4 lesions warranted surgical excision since more than
      90% of masses harbored intermediate or malignant pathology. The modified Bosniak
      classification system appears to allow for a reasonable clinical risk
      stratification of pediatric cystic renal masses.

PMID- 29572158
TI  - A Phase I/II Trial of the Combination of Azacitidine and Gemtuzumab Ozogamicin
      for Treatment of Relapsed Acute Myeloid Leukemia.
AB  - INTRODUCTION: Treatment with hypomethylating agent therapy might enhance anti
      CD33 monoclonal antibody-mediated cytotoxicity against acute myeloid leukemia
      (AML) blasts through epigenetic effects on Syk and SHP-1 expression. PATIENTS AND
      METHODS: In the present phase I/II study, we treated patients with relapsed or
      refractory AML with azacitidine, followed by 2 doses of gemtuzumab ozogamicin
      (GO) at 6 mg/m2, the Food and Drug Administration-approved dose and schedule at
      study initiation. We sought to determine the maximum tolerated dose and clinical
      activity of this combination therapy. Secondarily, we aimed to determine whether
      baseline Syk and SHP-1 expression can be used as predictive biomarkers of
      treatment response. RESULTS: The established maximum tolerated dose was
      azacitidine 75 mg/m2 daily for 6 consecutive days, followed by GO 6 mg/m2 on days
      7 and 21. Of the 50 evaluable patients, 12 (24%) obtained complete remission (CR)
      or CR with incomplete peripheral blood recovery (CRp). No dose-limiting
      toxicities were observed in phase I, and no patient developed hepatic sinusoidal
      obstructive syndrome. Although no significant correlation was found between Syk
      and SHP-1 expression and the clinical response to combination therapy, in vitro
      studies repeatedly demonstrated that azacitidine-treated AML cells had an
      increased response to GO treatment. CONCLUSION: Our study found that the
      combination of GO with azacitidine is relatively well tolerated, with response
      rates similar to those with GO monotherapy at higher doses. Differences in the GO
      drug schedule, dose level, and frequency might explain the discrepant response
      rates between our study and others, suggesting that the optimal GO dose remains
      unclear, especially when combined with hypomethylating agent therapy.

PMID- 29572159
TI  - Elderly Patients (Age 70 Years or Older) With Secondary Acute Myeloid Leukemia or
      Acute Myeloid Leukemia Developed Concurrently to Another Malignant Disease.
AB  - INTRODUCTION: Secondary acute myeloid leukemia (sAML) remains a therapeutic
      challenge. In elderly patients with AML, it is unclear whether sAML displays an
      inferior outcome compared with de novo AML. PATIENTS AND METHODS: We studied AML
      with an antecedent of hematologic disease, treatment-related AML, or AML
      occurring concurrently to another malignancy in a single-center cohort of
      patients aged 70 and older with AML. The study included 169 patients who were
      compared with a cohort of patients with de novo AML, without any prior history of
      malignant disorders, seen during the same period of time. RESULTS: Hematologic
      antecedents or presence of prior/concurrent solid malignancy did not impact
      complete remission rates and overall survival. In multivariate analysis, sAML
      appeared without independent prognostic value in the elderly. CONCLUSION: Our
      results support that sAML and de novo AML in elderly patients are not
      prognostically distinct entities. They should therefore not be considered
      separately when investigating outcomes and new treatment strategies.

PMID- 29572160
TI  - Biomaterials for drug delivery patches.
AB  - The limited efficiency of conventional drugs has been instigated the development
      of new and more effective drug delivery systems (DDS). Transdermal DDS, are
      associated with numerous advantages such its painless application and less
      frequent replacement and greater flexibility of dosing, features that triggered
      the research and development of such devices. Such systems have been produced
      using either biopolymer; or synthetic polymers. Although the first ones are
      safer, biocompatible and present a controlled degradation by human enzymes or
      water, the second ones are the most currently available in the market due to
      their greater mechanical resistance and flexibility, and non-degradation over
      time. This review highlights the most recent advances (mainly in the last five
      years) of patches aimed for transdermal drug delivery, focusing on the different
      materials (natural, synthetic and blends) and latest designs for the development
      of such devices, emphasizing also their combination with drug carriers that
      enable enhanced drug solubility and a more controlled release of the drug over
      the time. The benefits and limitations of different patches formulations are
      considered with reference to their appliance to transdermal drug delivery.
      Furthermore, a record of the currently available patches on the market is given,
      featuring their most relevant characteristics. Finally, a list of most
      recent/ongoing clinical trials regarding the use of patches for skin disorders is
      detailed and critical insights on the current state of patches for transdermal
      drug delivery are also provided.

PMID- 29572161
TI  - Host-pathogen dynamics through targeted secretome analysis of stimulated
      macrophages.
AB  - The pattern recognition receptors (PRRs) facilitate an organism's first line of
      defense against interlopers and shape the overall innate immune response through
      sensing and sampling pathogen-associated molecular patterns (PAMPs). The Toll
      like receptor (TLR) family is the prototypic PRR family. Upon recognition of
      PAMPs, TLRs promote MyD88 dependent and independent responses. Understanding how
      different PAMPs are recognized by their specific TLRs and how pathogen
      recognition initiates immune activation is an intense area of research.
      Previously, we have reported the discovery of the temporal changes in signaling
      cascades of macrophage proteome and secretome post-stimulation with three
      different PAMPs. To extend our global proteomics approach to targeted protein
      abundance quantification, we describe the macrophage secretome targeted
      proteomics assay. We chose three different pathogens that specifically stimulate
      diverse TLRs (TLR2, TLR4, and TLR7). Using a simple targeted proteomics approach,
      combining data-dependent acquisition with an inclusion list, an array of
      cytokines, chemokines, and transcription factors can be profiled for their
      secretome abundance. This strategy facilitates the profiling and validation of
      pathogen-specific temporal changes in the macrophage secretome.

PMID- 29572162
TI  - Integrated SWATH-based and targeted-based proteomics provide insights into the
      retinal emmetropization process in guinea pig.
AB  - : Myopia is generally regarded as a failure of normal emmetropization process,
      however, its underlying molecular mechanisms are unclear. To investigate the
      retinal protein profile changes during emmetropization, we studied differential
      protein expressions of ocular growth in young guinea pigs at 3 and 21 days old
      respectively, when significant axial elongation was detected (P < 0.001, n = 10).
      Independent pooled retinal samples of both eyes were subjected to SWATH mass
      spectrometry (MS) followed by bioinformatics analysis using cloud-based
      platforms. A comprehensive retina SWATH ion-library consisting of 3138 (22,871)
      unique proteins (peptides) at 1% FDR was constructed. 40 proteins were found to
      be significantly up-regulated and 8 proteins down-regulated during
      emmetropization (>=log2 of 0.43 with >=2 peptides matched per protein; P < 0.05).
      Using pathway analysis, the most significant pathway identifiable was
      'phototransduction' (P = 1.412e-4). Expression patterns of 7 proteins identified
      in this pathway were further validated and confirmed (P < 0.05) with high
      resolution Multiple Reaction Monitoring (MRM-HR) MS. Combining discovery and
      targeted proteomics approaches, this study for the first time comprehensively
      profiled protein changes in the guinea pig retina during normal emmetropization
      associated eye growth. The findings of this study are also relevant to the myopia
      development, which is the result of failed emmetropization. SIGNIFICANCE: Myopia
      is considered as a failure of emmetropization. However, the underlying
      biochemical mechanism of emmetropization, a visually guided process in which eye
      grows towards the optimal optical state of clear vision during early development,
      is not well understood. Retina is known as the key tissue to regulate this active
      eye growth. we studied eye growth of young guinea pigs and harvested their
      retinal tissues. A comprehensive SWATH ion library with identification of a total
      3138 unique proteins were established, in which 48 proteins exhibited significant
      differential expressions between 3 and 21 days old. After MRM-HR confirmation,
      'phototransduction' were found as the most active pathway during emmetropic eye
      growth. This study is the first in discovering key retinal protein players and
      pathways which are presumably orchestrated by biological mechanism(s) underlying
      emmetropization.

PMID- 29572163
TI  - The cardiac proteome in patients with congenital ventricular septal defect: A
      comparative study between right atria and right ventricles.
AB  - : Right ventricle (RV) remodelling occurs in neonatal patients born with
      ventricular septal defect (VSD). The presence of a defect between the two
      ventricles allows for shunting of blood from the left to right side. The
      resulting RV hypertrophy leads to molecular remodelling which has thus far been
      largely investigated using right atrial (RA) tissue. In this study we used
      proteomic and phosphoproteomic analysis in order to determine any difference
      between the proteomes for RA and RV. Samples were therefore taken from the RA and
      RV of five infants (0.34 +/- 0.05 years, mean +/- SEM) with VSD who were
      undergoing cardiac surgery to repair the defect. Significant differences in
      protein expression between RV and RA were seen. 150 protein accession numbers
      were identified which were significantly lower in the atria, whereas none were
      significantly higher in the atria compared to the ventricle. 19 phosphorylation
      sites (representing 19 phosphoproteins) were also lower in RA. This work has
      identified differences in the proteome between RA and RV which reflect
      differences in contractile activity and metabolism. As such, caution should be
      used when drawing conclusions based on analysis of the RA and extrapolating to
      the hypertrophied RV. SIGNIFICANCE: RV hypertrophy occurs in neonatal patients
      born with VSD. Very little is known about how the atria responds to RV
      hypertrophy, especially at the protein level. Access to tissue from age-matched
      groups of patients is very rare, and we are in the unique position of being able
      to get tissue from both the atria and ventricle during reparative surgery of
      these infants. Our findings will be beneficial to future research into heart
      chamber malformations in congenital heart defects.

PMID- 29572164
TI  - Surgical management of severe ocular surface injury due to Roman candle explosion
      accidents.
AB  - PURPOSE: To report the clinical features, management, and outcomes of patients
      with ocular surface damage secondary to Roman candle explosion accidents.
      METHODS: Retrospective, noncomparative, interventional case series of 11 patients
      with Roman candle explosion-related ocular surface injuries referred to the
      Cincinnati Eye Institute between 2007 and 2016. RESULTS: Eleven patients (10
      male, 1 female, mean age 22.4 years) sustained unilateral ocular surface injuries
      with presenting visual acuity ranging from count fingers to light perception. All
      patients had severe limbal stem cell deficiency with total ocular surface
      failure. Eight eyes received a conjunctival-limbal autograft (CLAU) with a
      keratolimbal allograft (KLAL), 1 eye received a living related-conjunctival
      limbal allograft (lr-CLAL) with a KLAL, and 2 eyes received a CLAU with lr-CLAL.
      Nine eyes underwent subsequent penetrating keratoplasty, and 7 eyes had
      reconstructive eyelid surgery. Nine eyes demonstrated improved visual acuity at
      last follow-up; seven eyes demonstrated a stable ocular surface at last follow
      up. Nonadherence was noted in 7 patients, either with poor adherence with post
      operative treatment or poor follow-up; this portended a worse visual result.
      CONCLUSIONS: Roman candle-related accidents can lead to severe ocular surface
      injury. Despite total ocular surface failure, these eyes can achieve good
      postoperative visual results following limbal stem cell transplantation and
      subsequent keratoplasty with appropriate compliance.

PMID- 29572165
TI  - Using Recent BCI Literature to Deepen our Understanding of Clinical
      Neurofeedback: A Short Review.
AB  - In their recent paper, Alkoby et al. (2017) provide the readership with an
      extensive and very insightful review of the factors influencing NeuroFeedback
      (NF) performance. These factors are drawn from both the NF literature and the
      Brain-Computer Interface (BCI) literature. Our short review aims to complement
      Alkoby et al.'s review by reporting recent additions to the BCI literature. The
      object of this paper is to highlight this literature and discuss its potential
      relevance and usefulness to better understand the processes underlying NF and
      further improve the design of clinical trials assessing NF efficacy. Indeed, we
      are convinced that while NF and BCI are fundamentally different in many ways,
      both the BCI and NF communities could reach compelling achievements by building
      upon one another. By reviewing the recent BCI literature, we identified three
      types of factors that influence BCI performance: task-specific,
      cognitive/motivational and technology-acceptance-related factors. Since BCIs and
      NF share a common goal (i.e., learning to modulate specific neurophysiological
      patterns), similar cognitive and neurophysiological processes are likely to be
      involved during the training process. Thus, the literature on BCI training may
      help (1) to deepen our understanding of neurofeedback training processes and (2)
      to understand the variables that influence the clinical efficacy of NF. This may
      help to properly assess and/or control the influence of these variables during
      randomized controlled trials.

PMID- 29572166
TI  - The Effects of N-terminal Mutations on beta-amyloid Peptide Aggregation and
      Toxicity.
AB  - Human amyloid beta1-42 (hAbeta1-42) peptides are known to self-aggregate into
      oligomers that contribute to the degeneration of neurons and development of
      Alzheimer's disease (AD) pathology. Unlike humans, rodents do not develop AD,
      possibly due to differences in three amino acids (R5G, Y10F and H13R) within the
      hydrophilic N-terminal domain of Abeta1-42. This is partly supported by evidence
      that hAbeta1-42 is more prone to fibrillization and has a higher cellular
      toxicity than rodent Abeta1-42 (rAbeta1-42). Mutagenesis studies, however, have
      shown that correlation between fibrillization potential and toxicity is not
      always direct. Thus, to understand better how N-terminal mutations can affect
      hAbeta1-42 toxicity through oligomerization, we evaluated fibrillization
      kinetics, oligomer sizes and toxicity profiles of double mutant (human toward
      rodent) Abeta1-42. Additionally, we tested the mutant peptides in combination
      with hAbeta1-42, to assess effects on hAbeta1-42 aggregation/toxicity. Our
      results clearly show that double mutations to humanize rAbeta1-42 result in a
      significantly reduced efficiency of fibril formation, as determined by Thioflavin
      T aggregation assays and confirmed with electron micrographic studies.
      Interestingly, the mutants are still able to aggregate into oligomers, which are
      predominantly larger than those comprised of hAbeta1-42. Our cell viability
      experiments further showed a rank order of oligomer toxicity of hAbeta1-42 >
      rAbeta1-42 ? mutant Abeta1-42, suggesting that toxicity can be influenced by N
      terminal Abeta1-42 mutations via reduction of fibril formation and/or alteration
      of oligomer size. These results, taken together, confirm that N-terminal
      mutations can affect Abeta fibril and oligomer formation with reduced toxicity
      despite lying outside the core amyloid region of Abeta peptide.

PMID- 29572167
TI  - Radiologic Analysis of Kinematic Characteristics of Modic Changes Based on Lumbar
      Disc Degeneration Grade.
AB  - OBJECTIVE: The kinematic characteristics of Modic changes (MCs) in the lumbar
      spine have rarely been reported; furthermore, the effect of disc degeneration
      (DD) on segmental motion has not been considered in analyzing the motion
      characteristics of MCs. Therefore, this study was designed to evaluate the
      kinematic characteristics of MCs based on different DD grades. METHODS: 894
      patients with 4470 lumbar segments were reviewed, and those with MCs were
      selected for segmental motion evaluation. MC type was defined as 0, I, II, and
      III, and DD grade was classified into 5 groups from grade A to grade E. Segmental
      angular and translational motion were calculated from X-ray images in positions
      of flexion and extension, and the absolute values of the differences were
      recorded. RESULTS: MCs were observed in 308 segments from 260 patients. No MC was
      found in DD grade A, and MC III was not observed in DD grade B. MC I was found to
      significantly increase angular motion in the DD grade E group, and MC II could
      enlarge translational motion in the DD grade D group (all P < 0.05); MC III had
      the lowest segmental motion in both angular and translational motion; There was
      no statistical difference in angular and translational motion between MC I and II
      in all DD grade groups (all P > 0.05). CONCLUSIONS: MC III indicates the final
      stable phase of segmental motion. MC I might increase angular motion, and MC II
      would increase certain translational motions in the segments that were believed
      to be stable.

PMID- 29572168
TI  - Lymphocytic Hypophysitis Secondary to Ruptured Rathke Cleft Cyst: Case Report and
      Literature Review.
AB  - BACKGROUND: Lymphocytic hypophysitis is a rare inflammatory lesion in the sellar
      region. Lymphocytic hypophysitis secondary to ruptured Rathke cleft cyst (RCC) is
      even more rarely seen. Clinical characteristics, treatment strategies, and
      prognosis remain elusive. CASE DESCRIPTION: A 58-year-old Chinese woman with a 3
      year history of intermittent headache and new development of polydipsia,
      polyuria, and binocular visual acuity decline over the past 4 months was admitted
      to our hospital. On admission, endocrine results were normal. Ophthalmic testing
      showed bitemporal visual field deficits and decreased visual acuity of both eyes.
      Pituitary dynamic magnetic resonance imaging showed a cystic sellar lesion
      measuring 5.6 * 5.2 * 6.2 mm with tumor shrinkage compared with initial
      neuroimaging. Transsphenoidal surgery was performed for tumor resection. An
      additional biopsy of the anterior pituitary lobe was performed because of
      intraoperative abnormal appearances of the pituitary gland. Pathology
      examinations revealed the specimen of the cystic lesion to be RCC and exhibited
      infiltration of massive lymphocytes, diffused plasmocytes, and eosinophils that
      were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe.
      During follow-up, the lesion of lymphocytic hypophysitis showed spontaneous
      shrinkage in the absence of steroid treatment after RCC resection. Final
      diagnosis was lymphocytic hypophysitis secondary to ruptured RCC. CONCLUSIONS: We
      present a rare case of lymphocytic hypophysitis secondary to ruptured RCC and
      provide clinical data of such lesions in the literature. Full understanding of
      the clinical features plays an important role in diagnosis and treatment of
      lymphocytic hypophysitis secondary to ruptured RCC.

PMID- 29572169
TI  - Surgical Management of Adverse Radiation Effects After Gamma Knife Radiosurgery
      for Cerebral Arteriovenous Malformations: A Population-Based Cohort Study.
AB  - OBJECTIVE: The goal of this study is to report our experience in the surgical
      treatment of cerebral arteriovenous malformations (cAVMs) related permanent
      symptomatic adverse radiation effects (PSAREs), to clarify an appropriate
      surgical management and to identify the risk factors related to their
      development. METHODS: We evaluated 549 patients treated with Gamma Knife
      radiosurgery (GKRS) for cAVMs with a follow-up of at least 8 years. Univariate
      and multivariate analyses were used to test different risk factors related to the
      development of PSARE. We retrospectively reviewed the records of these patients
      to analyze the clinical outcome. RESULTS: Fourteen patients (2.5%) developed
      PSARE and were submitted to surgery. Higher average treated volume represents a
      significant risk factors for the development of PSARE (P < 0.05); on the other
      hand, older age and higher average dose reduce the risk of PSARE (P < 0.05). A
      favorable clinical outcome was achieved in 13 patients (93%) after surgery; in 1
      patient, the unfavorable outcome was due to hemorrhage that occurred months after
      GKRS. Serial MRI scans following either surgical removal of the nodule or Ommaya
      reservoir positioning showed progressive reduction of brain edema in all cases.
      CONCLUSIONS: The management of PSARE is controversial, especially for cAVMs
      treated with SRS. Surgical removal is rarely needed, but-if unavoidable-it can be
      a valuable option in experienced hands. A careful preoperative planning is always
      necessary to detect pathologic blood flow through the PSARE.

PMID- 29572170
TI  - Favorable Long-Term Outcomes for Positional Vertebral Artery Occlusion with
      Treatment Strategy Prioritizing Spinal Fusion Surgery.
AB  - OBJECTIVE: Positional vertebral artery occlusion (PVAO) has a fundamental problem
      in the definition. We analyzed the long-term outcomes with a redefinition of the
      rare clinical entities as PVAO for a broader conceptualization, and discuss the
      efficacy of fusion surgery as a treatment option. METHODS: We analyzed the
      clinical and radiologic characteristics and outcomes in 8 patients with PVAO who
      experienced cerebral ischemia during a 10-year period at our institution. The
      follow-up periods ranged from 60 to 132 months (mean, 93.5 months). All patients
      were initially treated conservatively with external fixation. If spinal
      instability was observed at the initial evaluation or a second stroke occurred
      during conservative treatment, cervical spinal fusion was performed with special
      consideration for vertebral artery dominance and the presence of its collateral
      flow regardless of the type of stroke. RESULTS: Conservative therapy was
      completed for 2 patients, and spinal fusion was performed for the other 6
      patients. None of the patients experienced a recurrence of symptoms after
      discharge until the final follow-up visit, and the outcomes were excellent. Long
      term functional outcomes were dependent on the patient's condition before the
      onset of stroke and the neurologic deficits resulting from the initial or
      recurrent stroke induced by embolism. CONCLUSIONS: We report our single-center
      experience with PVAO in which 75% of patients had embolic stroke. Because embolic
      stroke may have a greater risk of recurrence affecting the long-term outcomes, it
      should be prevented. In addition, if surgical intervention is necessary, spinal
      fusion surgery may be an effective option.

PMID- 29572171
TI  - Rare Case of Cerebrospinal Fluid Proctorrhea Caused by Anterior Sacral
      Meningocele with Rectothecal Fistula.
AB  - BACKGROUND: Anterior sacral meningocele (ASM) leading to secondary rectothecal
      fistula is extremely rare, and to date only 5 such cases have been described in
      the world literature. CASE DESCRIPTION: We describe an uncomplicated case of a 52
      year-old female patient presenting with cerebrospinal fluid leak from the anus
      who was investigated and found to have an ASM with rectothecal fistula. The ASM
      and rectothecal fistula were subsequently repaired using a posterior approach.
      Pertinent literature review, clinical findings, neuroimaging, and surgical
      management are described for these rare lesions. CONCLUSION: Early diagnosis and
      surgical disconnection of the fistulous tract led to satisfactory outcome in the
      present case and avoided the catastrophic complication of meningitis.

PMID- 29572172
TI  - Double Retrotransverse Foramen of Atlas (C1).
AB  - BACKGROUND: The retrotransverse foramen is a nonmetric variant of C1 that
      consists of an abnormal accessory foramen on the posterior root of the transverse
      process. CASE DESCRIPTION: During a study on the prevalence of the
      retrotransverse foramen in 150 dry C1 vertebrae, we observed an exceptional C1
      (0.67%) with a right double retrotransverse foramen of the 14 C1 vertebrae
      (9.3%). This has not been reported previously in the literature. No osteogenic
      reaction and no degenerative signs were observed in this C1 with the double
      retrotransverse foramen. CONCLUSIONS: Neurosurgeons should be aware of the
      possible presence of the "conventional" retrotransverse foramen and the
      "exceptional" double retrotransverse foramen so that they can safely plan to
      prevent surgical complications. This will thus ensure better patient management
      by neurosurgeons.

PMID- 29572173
TI  - Life Expectancy of Brazilian Neurosurgeons.
AB  - BACKGROUND: Life expectancy (LE) refers to the number of years that an individual
      is expected to survive. Emphasis is frequently placed on the relationship between
      LE and the conditions under which a population lives, but fewer studies have
      investigated the relationship between stress factors associated with specific
      professions and their effects on LE. The aim of this study is to evaluate
      Brazilian neurosurgeons' life expectancies (BNLEs) and compare them with those of
      physicians (both Brazilian and foreign) from other fields, as well as with
      Brazilian nondoctors. METHODS: The Brazilian Society of Neurosurgery death
      registry was used to obtain data that compared LEs from non-neurosurgeon
      physicians, as described in the national and international literature. BNLEs were
      also compared with the LEs of Brazilian citizens. RESULTS: Fifty-one
      neurosurgeons died between 2009 and 2016. All were males. The mean age at death
      was 68.31 +/- 17.71 years. Among all-cause mortality, the breakdown was 20%
      cardiovascular diseases, 39% malignancies, 10% external factors, 6%
      gastrointestinal disorders, 12% neurologic illnesses, and 14% unknown causes.
      BNLE was shorter than LE of male Brazilian citizens. CONCLUSIONS: LE was similar
      among neurosurgeons and other doctors but shorter compared with Brazilian
      citizens. Further research is needed to provide data that can add to and confirm
      these results.

PMID- 29572174
TI  - Entire Orifice Blocking-Assisted Microsurgical Treatment: Clipping of
      Intracranial Giant Wide-Neck Paraclinoid Aneurysms.
AB  - OBJECTIVE: Giant wide-neck paraclinoid aneurysms remain a formidable challenge
      for neurosurgeons due to the brisk retrograde blood flow during surgical
      clipping. Theoretically, Entire orifice blockade (EOB) by placing a longitudinal
      intracarotid balloon catheter across the aneurysm neck could achieve a good
      vascular control in treating cerebral aneurysms, but related studies have been
      scarce. The aim of this study was to evaluate the safety and efficiency of the
      EOB-assisted microsurgical technique for treating giant wide-neck paraclinoid
      aneurysms. METHODS: Clinical data and treatment summaries of patients with giant
      wide-neck paraclinoid aneurysms who underwent EOB-assisted microsurgical clipping
      were retrospectively reviewed. RESULTS: A total of 26 patients were analyzed. All
      but 3 patients harbored unruptured aneurysms. The mean largest diameter of the
      aneurysms was 26.8+/-2.0 mm, and the mean neck size was 12.5+/-2.4 mm. All
      lesions were successfully clipped without residual aneurysms. Post-operative
      images revealed no major branch occlusion due to thromboembolic complications.
      Four patients presented neurologic deficits caused by vasospasm, 3 of which were
      completely resolved by postoperative treatment. At a mean follow-up time of 1.86
      +/- 0.95 years (range, 0.5-3.5 years), none of the patients died, and 96.2% (n =
      25) of the patients had favorable clinical outcomes with modified Rankin Scale
      values of 0-2. CONCLUSIONS: For patients with giant wide-neck paraclinoid
      aneurysms, EOB-assisted microsurgical clipping is a safe and useful procedure for
      obtaining vascular control, for softening and shrinking the aneurysm sac and for
      providing a wide and clean operative field that allows the clip to be effectively
      placed.

PMID- 29572175
TI  - Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An
      Experimental Rat Model.
AB  - BACKGROUND: Immediate microsurgical nerve suture remains the gold standard after
      peripheral nerve injuries. However, functional recovery is delayed, and it is
      satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation
      proximal to the lesion enhances nerve regeneration and muscle reinnervation. This
      study aims to evaluate the effects of the motor cortex electrical stimulation on
      peripheral nerve regeneration after injury. METHODS: Eighty rats underwent right
      sciatic nerve section, followed by immediate microsurgical epineural sutures.
      Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical
      stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just
      proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15
      minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed
      over the course of two weeks after nerve suture (MCSc). Assessment included
      electrophysiology and motor functional score at day 0 (baseline value before
      nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological
      study at week 12. RESULTS: Our results showed that MCS enhances functional
      recovery, nerve regeneration, and muscle reinnervation starting week 4 compared
      with the control group (P < 0.05). The MCS induces higher reinnervation rates
      even compared with peripheral stimulation, with better results in the MCSa group
      (P < 0.05), especially in terms of functional recovery. CONCLUSIONS: MCS seems to
      have a beneficial effect after peripheral nerve injury and repair in terms of
      nerve regeneration and muscle reinnervation, especially when acute mode is used.

PMID- 29572176
TI  - Perineural Spread of Nonmelanoma Skin Cancer to the Brachial Plexus: Identifying
      Anatomic Pathway(s).
AB  - BACKGROUND: Perineural spread leading to brachial plexopathy has recently been
      described in cases of melanoma. The occurrence and mechanism for nonmelanoma skin
      cancer spread to the brachial plexus is poorly understood. METHODS: A
      retrospective chart review of the Mayo Clinic database was conducted to identify
      patients with nonmelanoma skin cancer and brachial plexopathy between 2000 and
      2017. Inclusion criteria were a history of nonmelanoma skin cancer, a clinical
      diagnosis of brachial plexopathy, imaging features of perineural spread, and a
      positive result of examination of a biopsy specimen showing tumor in a skin
      nerve. RESULTS: Thirty-seven patients with a history of nonmelanoma skin cancer
      and brachial plexopathy were identified. Inclusion criteria were fulfilled in 2
      cases of cutaneous squamous cell carcinoma. One case of recurrent basal cell
      carcinoma with perineural spread confirmed in the brachial plexus by pathologic
      examination was excluded because confirmatory evidence of perineural spread from
      the skin to the brachial plexus was not available. CONCLUSIONS: Perineural spread
      of nonmelanoma skin cancer leading to brachial plexopathy is rare. Our 2 cases
      and the cases found in the literature demonstrate different entry points to the
      neural highway resulting in neurologic deficits. The cervical plexus serves as a
      hub for further spread in certain cases of perineural spread of skin cancer.

PMID- 29572177
TI  - Metastatic Spine Tumor Epidemiology: Comparison of Trends in Surgery Across Two
      Decades and Three Continents.
AB  - BACKGROUND: Indications for surgery for symptomatic spinal metastases have become
      better defined in recent years, and suitable outcome measures have been
      established against a changing backdrop of patient characteristics, tumor
      behavior, and oncologic treatments. Nonetheless, variations still exist in the
      local management of patients with spinal metastases. In this study, we aimed to
      review global trends and habits in the surgical treatment of symptomatic spinal
      metastases, and to examine how these have changed over the last 25 years.
      METHODS: In this cohort study of consecutive patients undergoing surgery for
      symptomatic spinal metastases, data were collected using a secure Internet
      database from 22 centers across 3 continents. All patients were invited to
      participate in the study, except those unable or unwilling to give consent.
      RESULTS: There was a higher incidence of colonic, liver, and lung carcinoma
      metastases in Asian countries, and more frequent presentation of breast,
      prostate, melanoma metastases in the West. Trends in surgical technique were
      broadly similar across the centers. Overall survival rates after surgery were 53%
      at 1 year, 31% at 2 years, and 10% at 5 years after surgery (standard error 0.013
      for all). Survival improved over successive time periods, with longer survival in
      patients who underwent surgery in 2011-2016 compared with those who underwent
      surgery in earlier time periods. CONCLUSIONS: Surgical habits have been fairly
      consistent among countries worldwide and over time. However, patient survival has
      improved in later years, perhaps due to medical advances in the treatment of
      cancer, improved patient selection, and operating earlier in the course of
      disease.

PMID- 29572178
TI  - Long noncoding RNA BDNF-AS is downregulated in cervical cancer and has anti
      cancer functions by negatively associating with BDNF.
AB  - PURPOSE: We investigated expression and mechanism long noncoding RNA BDNF-AS in
      human cervical cancer (CC). METHODS: BDNF-AS expressions were examined by qPCR in
      CC cell lines and human CC tumors. CC cell lines, SiHa and DoTc2-4510 were
      transduced with lentivirus to ectopically overexpress BDNF-AS. Possible anti
      cancer effects of BDNF overexpression were examined on CC in vitro proliferation
      and migration, and in vivo transplantation. Human BDNF gene expression was also
      examined in CC cell lines and tumors. In CC cells with overexpressed BDNF-AS,
      BDNF was upregulated to examine its direct effect in NDNF-AS-modulated CC
      proliferation and migration. RESULTS: BDNF was downregulated in both CC cells and
      human CC tumors. In CC cells, BDNF-AS overexpression is anti-cancer by inhibiting
      proliferation and migration in vitro, and transplantation in vivo. BDNF was
      inversely expressed as BDNF-AS in CC. Upregulation of BDNF in BDNF-AS
      overexpressed CC cells reversed the anti-cancer effects of BDNF-AS. CONCLUSION:
      BDNF-AS is downregulated in CC. Overexpressing BDNF-AS may inhibit CC, possibly
      through inverse regulation on BDNF.

PMID- 29572179
TI  - Continuous application of compressive force induces fusion of osteoclast-like
      RAW264.7 cells via upregulation of RANK and downregulation of LGR4.
AB  - AIMS: During orthodontic treatment, facilitating osteoclastic bone resorption in
      the alveolar bone exposed to the compressive force (CF) is an important factor
      for tooth movement. The present study investigated the effect of CF stimulation
      on the differentiation of RAW264.7 cells from precursors to mature osteoclasts.
      MAIN METHODS: The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm2
      CF-which was generated by increasing the volume of culture medium in the wells of
      a 96-well plate-in the presence or absence of receptor activator of nuclear
      factor kappaB (RANK) ligand (RANKL) for 4 days. KEY FINDINGS: In the presence of
      RANKL, the number of tartrate-resistant acid phosphatase (TRAP)-positive
      multinucleated cells and the mRNA levels of dendritic cell-specific transmembrane
      protein (DC-STAMP) and osteoclast-stimulatory transmembrane protein (OC-STAMP)
      were increased by application of 0.6 and 1.1 g/cm2 CF as compared to 0.3 g/cm2
      CF. The mRNA level of RANK was upregulated whereas that of leucine-rich repeat
      containing G-protein-coupled receptor (LGR)4-another RANKL receptor was
      downregulated by 0.6 and 1.1 g/cm2 CF as compared to 0.3 g/cm2 CF in the absence
      of RANKL. The proportion of cells with nuclear translocation of the nuclear
      translocation of nuclear factor of activated T cells (NFAT)c1 was increased by
      0.6 and 1.1 g/cm2 CF in the presence of RANKL. SIGNIFICANCE: Continuous
      application of CF induced the differentiation of RAW264.7 cells into TRAP
      positive multinuclear cells by enhancing the expression of DC- and OC-STAMP and
      the nuclear translocation of NFATc1. This may result from the CF-induced increase
      in RANK and decrease in LGR4 expression.

PMID- 29572180
TI  - Two tandem repeats of mHSP70407-426 enhance therapeutic antitumor effects of a
      recombined vascular endothelial growth factor (VEGF) protein vaccine.
AB  - AIMS: Active immunization with human vascular endothelial growth factor (hVEGF)
      vaccines provides a therapeutic option instead of bevacizumab therapy. However,
      the immunity to self-molecule is difficult to elicit due to immune tolerance. A
      bioactive peptide of two tandem repeats of mHSP70407-426 (M2) has exhibited
      potent adjuvant ability in our previous study, and the aim of this study was to
      explore whether M2 could assist hVEGF to display enhanced therapeutic anti-tumor
      effects. MAIN METHODS: The anti-tumor effects of hVEGF-M2 vaccine were evaluated
      in both H22 hepatocellular carcinoma and Lewis lung tumor models. CD31 analysis
      of excised tumors was used to evaluate anti-angiogenesis effects. The titers of
      anti-VEGF antibody was detected by ELISA and verified by western blot analyses,
      and the effects of immune sera on HUVEC differentiation were investigated by tube
      formation assay. KEY FINDINGS: M2 could assist hVEGF to exhibit more favorable
      therapeutic anti-tumor growth and metastasis effects than hVEGF. Meanwhile, high
      titer of anti-VEGF antibody was detected in hVEGF-M2 immunized mice sera by ELISA
      and verified by western blot analysis. Sera from hVEGF-M2 immunized mice could
      more significantly inhibit HUVEC tube formation than hVEGF immune serum. The
      hVEGF-M2-immune sera could more effectively inhibit H22 tumor growth and extend
      the survival rates of H22 tumor bearing mice than hVEGF-immune sera. CD31
      analysis of the excised tumors verified a significant reduction in vessel density
      after hVEGF-M2 vaccination. SIGNIFICANCE: M2 could assist hVEGF to display
      enhanced anti-tumor effects, which are important for the further application of
      M2 to enhance antigen-specific immune responses.

PMID- 29572182
TI  - Opening-wedge high tibial osteotomy performed with locking plate fixation
      (TomoFix) and early weight-bearing but without filling the defect. A concise
      follow-up note of 48 cases at 10 years' follow-up.
AB  - INTRODUCTION: Use of a locking plate during medial opening high tibial osteotomy
      (HTO) eliminates the need to fill the defect and its associated complications. It
      also allows early weight-bearing. Since long-term data with this type of
      construct are rare, we wanted to report the outcomes of a 51-patient cohort
      evaluated after a mean follow-up of 10.2years. The goals were to determine (1)
      the HTO survival and whether the correction was maintained between 2 and 10years
      later, (2) the stability of the functional outcomes, (3) the complication rate
      related to use of locking plates. HYPOTHESIS: The correction following medial
      opening HTO with a TomofixTM plate without void filling is maintained after
      10years' follow-up. MATERIAL AND METHODS: Fifty-one patients ranging from 37 to
      72years of age at the time of surgery between 2003 and 2005 underwent a medial
      opening HTO that was stabilized with a TomofixTM locking plate (Synthes,
      Oberdorf, Switzerland) without void filling. Forty-eight patients were reviewed
      between March and September 2014; 1 patient had died and 2 were lost to follow
      up. RESULTS: The mean HKA angle went from 172+/-3.18 degrees  (165-178 degrees )
      preoperatively to 181+/-1.18 degrees  (176-185 degrees ) postoperatively, to
      181+/-1.60 degrees  (176-185 degrees ) at 2years, and 180.8+/-2.4 degrees  (175
      184 degrees ) at 10years' follow-up. This equates to a loss of correction of
      0.71+/-1.9 degrees  (0-6 degrees ) (p=0.02) between 2 and 10years after the
      surgery. Five patients underwent total knee arthroplasty (TKA), thus the 10-year
      survival of the HTO procedure was 88% (95% CI: 81-98%). If the five TKA
      procedures are excluded, the mean IKS knee score went from 90+/-7.4 (66-98) at
      2years' follow-up to 77+/-15.3 (43-97) at 10years (p>0.05). There were four
      complications in all (8%), of which three occurred within 2years (2 cases of
      nonunion and 1 surgical site infection) and one occurred later (infection after
      118months that resolved once the hardware was removed and the patient given
      appropriate antibiotics). There were no complications related to the five
      subsequent TKA procedure and no bone grafting was required. DISCUSSION: There was
      a small (less than 1 degree) but statistically significant loss of correction and
      non-significant deterioration in the functional outcomes. Conversely, the
      complication rate did not increase over time, despite the lack of void filling,
      particularly in patients who subsequently underwent TKA. The 10-year survival was
      similar to other HTO procedures. This locking plate construct without void
      filling is reliable after 10years. LEVEL OF EVIDENCE: Level IV, prospective study
      without control group.

PMID- 29572181
TI  - Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein
      synthesis pathway.
AB  - AIMS: The present study aims to investigate the role of Akt in the regulation of
      urinary bladder organ hypertrophy caused by partial bladder outlet obstruction
      (pBOO). MAIN METHODS: Male rats were surgically induced for pBOO. Real-time PCR
      and western blot were used to examine the levels of mRNA and protein. A
      phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the
      activity of endogenous Akt. KEY FINDINGS: The urinary bladder developed
      hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I
      collagen and alpha-smooth muscle actin (alphaSMA) were increased in pBOO bladder
      when compared to sham control. The phosphorylation (activation) levels of Akt1 (p
      Ser473), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1
      were also increased in pBOO bladder. LY294002 treatment reduced the
      phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I
      collagen and alphaSMA in pBOO bladder. The mRNA and protein levels of
      proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and
      PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment
      had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002
      treatment partially reduced the bladder weight caused by pBOO. SIGNIFICANCE: pBOO
      induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle
      cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated
      protein synthesis in pBOO bladder contributes to type I collagen and alphaSMA but
      not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in
      treatment of urinary bladder hypertrophy following pBOO.

PMID- 29572183
TI  - TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a
      patient with a deletion of 13Mb on chromosome 6.
AB  - There is scarce literature about autoinflammation in syndromic patients. We
      describe a patient who, in addition to psychomotor and growth delay, presented
      with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers.
      Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb
      deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene
      (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts
      inflammation via its deubiquitinase activity. Western blotting and
      immunoprecipitation assays showed decreased A20 expression and increased
      phosphorylation of p65 and IkBa. Patient's cells displayed increased levels of
      total K63-linked ubiquitin and increased levels of ubiquitinated RIP and NEMO
      after stimulation with TNF. We describe the molecular characterization of an
      autoinflammatory disease due to a large chromosomal deletion and review the
      phenotypes of patients with A20 haploinsufficiency. CGH arrays should be the
      first diagnostic method for comprehensive analysis of patients with syndromic
      features and immune dysregulation.

PMID- 29572184
TI  - Predictive utilities of neutrophil gelatinase-associated lipocalin (NGAL) in
      severe sepsis.
AB  - BACKGROUND: We aim to investigate the predictive value of plasma neutrophil
      gelatinase-associated lipocalin (pNGAL) in patients with severe sepsis. METHODS:
      A total of 124 patients were enrolled in this observational study. Blood samples
      were obtained at admission, on day 2 and day 7. Receiver operating characteristic
      (ROC) curves were generated to assess the utility of pNGAL in prediction of 28
      day mortality and need for CRRT. Cox regression curves were built with and
      without pNGAL for 28-day mortality prediction to determine NGAL's contributive
      predictive value. RESULTS: Plasma NGAL was significantly increased in non
      survivors group on day 2 and 7 and predicted 28-day mortality with AuROC values
      of 0.675 (95% CI 0.570-0.780) and 0.752 (95% CI 0.619-0.885). Addition of day 2
      NGAL to the clinical model resulted in a net reclassification index (NRI)
      increment of 0.40 (95% CI 0.06-0.75, P = 0.028) for prediction of 28-day
      mortality. The AuROC of NGAL at admission and day 2 was greater than creatinine
      in prediction of the need for CRRT. CONCLUSION: Plasma NGAL discriminated 28-day
      survivors from non-survivors on day 2 and 7 and was a relatively robust predictor
      of 28-day mortality prediction. Plasma NGAL possibly outperformed creatinine in
      the prediction of need for CRRT.

PMID- 29572185
TI  - C-reactive protein and emergency department seven days revisit.
AB  - BACKGROUND: Emergency department (ED) revisit might be partially preventable. C
      reactive protein (CRP) is an inflammatory biomarker which is commonly used as
      screening tool in the ED. We sought to evaluate the association between CRP level
      in patients visiting emergency department and 7 days revisit after discharge.
      METHODS: A historical cohort study of all patients who visited the internal
      division of the emergency department between June 2007 and July 2017 and had a
      CRP test. New ED visit was defined when neither any emergency department visit
      nor any hospital admission was recorded in our files during the previous 90 days.
      Univariate and multivariate models were used to evaluate the association between
      CRP and 7 days ED revisit. RESULTS: The study included 135,476 patients with
      173,443 new visits. In 101,181 (58.3%) visits the patients were released and 7077
      (7%) of them were revisited in 7 days. Even mild elevated CRP (5-25 mg/L) was
      independently associated with significant risk for revisit (OR 1.27, 95% CI 1.20
      1.35). CONCLUSION: CRP is an independent predictor for 7 days ED revisit and
      should be considered at the time of discharge. Prediction models for ED revisit
      should include CRP as a potential predictor in their models.

PMID- 29572187
TI  - Joggin' the Noggin: Towards a Physiological Understanding of Exercise-Induced
      Cognitive Benefits.
AB  - This narrative review examines literature pertaining to possible physiological
      explanations for observed cognitive benefits stemming from improvements to
      cardiovascular fitness following chronic aerobic exercise. Studies regarding
      exercise and cardiovascular fitness, angiogenesis, neuroinflammation in relation
      to IGF-1 signalling, regulation of neurotrophins, neurogenesis and plasticity,
      cognitive training, are briefly described. We propose that current evidence
      points towards a mechanism by which cardiovascular fitness improvements act to
      promote long-term angiogenesis and cerebral circulation. This important
      adaptation allows for increased delivery and upregulation of neurotrophins along
      with supporting factors to the brain, particularly to the hippocampal neurogenic
      niche, following acute exercise bouts. We propose a sequential timeline and
      approximate time scale for this mechanism, describing how these stages generate
      increased support for neurogenesis and brain plasticity in combination with
      cognitive training to provide long-term cognitive benefits and protection against
      age-related cognitive decline. Influences from age, gender and other variables
      are considered, and methodological factors that could be utilised in future
      studies to further clarify the proposed model are discussed.

PMID- 29572186
TI  - Biomarker potential of IL-6 and VEGF-A in ascitic fluid of epithelial ovarian
      cancer patients.
AB  - BACKGROUND: Ovarian cancer is represented with significantly higher mortality
      rate predominately due to asymptomatic behaviour during initial disease course
      and at diagnosis majority patients already progressed to advanced stage.
      Acellular fraction of ascites in epithelial ovarian cancer (EOC) has been
      suggested to promote growth of tumor cells by providing ambient micro-environment
      for their proliferation. This acellular fraction contains multiple growth factors
      including IL-6 and VEGF-A, which were exploited to establish their bio-marker
      significance in EOC patients. METHODS: IL-6 and VEGF-A levels in ascitic fluid of
      30 EOC patients and 15 controls were measured using high sensitivity sandwich
      enzyme linked immune sorbent (ELISA) assay. Their levels were correlated with
      clinico-pathological characteristics and bio-marker potential was assessed.
      RESULTS AND CONCLUSION: EOC patients showed significantly higher levels for IL-6
      (median-5636 pg/ml) and VEGF-A (median-4556 pg/ml) in ascitic fluid compared to
      controls. Levels of IL-6 and VEGF-A significantly correlated with clinico
      pathological parameters. ROC curves of IL-6 and VEGF-A showed absolute
      combination of sensitivity and specificity. Kaplan Meier analysis demonstrated
      that higher levels of IL-6 and VEGF-A were significantly associated with shorter
      progression free survival. Thus, this study revealed that IL-6 and VEGF-A have
      great potential to be used as superior bio-markers for progression free survival
      in future after validation in larger patients' cohort.

PMID- 29572188
TI  - Long-term cognitive outcomes in male and female athletes following sport-related
      concussions.
AB  - Despite concussion being a serious public health concern and the increasing
      participation of female athletes in sport, the comparative long-term outcomes of
      male and female athletes are poorly understood, potentially limiting the
      scientific understanding and clinical management of these injuries. We examined
      whether sex influences the long-term cognitive outcomes in athletes with a
      history of concussion (HOC; 6+ months from injury). Accordingly, 196 asymptomatic
      student-athletes participated in the study (98 with a HOC; 98 matched controls).
      The sample included both male (n = 98) and female athletes (n = 98). Participants
      completed the Cogstate brief battery, to which we added a 2-Back condition to
      increase cognitive load. As predicted, the results revealed sex differences on
      the N-back Task, a measure of executive functions, with female athletes having a
      HOC responding significantly more slowly than their male counterparts on the 2
      Back condition (p = 0.02). Moreover, irrespective of sex, athletes with a HOC
      were slower and less accurate relative to controls on the N-back Task (p = 0.01).
      Analyses failed to reveal any significant sex or group difference on tasks that
      measure lower-level cognition (ps > 0.05). The current results reaffirm the
      presence of subtle, yet long-term alterations in aspects of executive functions
      following a sport-related concussion. More importantly, our results highlight
      that female athletes exhibit alterations of greater magnitude than their male
      counterparts. Therefore, the sex difference observed in the days or weeks
      following a concussion may persist well into the chronic phase of injury.

PMID- 29572189
TI  - Inflammation-restricted anti-inflammatory activities of a N-acylethanolamine acid
      amidase (NAAA) inhibitor F215.
AB  - N-Acylethanolamine acid amidase (NAAA) is a cysteine enzyme that catalyzes the
      hydrolysis of palmitoylethanolamide (PEA). Pharmacological blockage of NAAA
      elevates PEA levels and exerts powerful anti-inflammatory activities. We have
      recently identified a highly potent NAAA inhibitor F215. Here, we demonstrated
      that F215 was an unusual inflammation-restricted NAAA inhibitor. In
      lipopolysaccharides (LPS) induced acute lung injury (ALI) model, F215 markedly
      accelerated inflammation resolution, promoted clearance of neutrophils
      infiltration and alveolar repair in the lungs. F215 efficiently inhibited NAAA
      and protected endogenous PEA from degradation in ALI model, but it cannot readily
      suppress the NAAA activity in naive mice. The inflammation-restricted effect of
      F215 was further confirmed in the alveolar macrophage, F215 only increased PEA
      levels and exerted anti-inflammatory effects in activated macrophages, but not in
      unstimulated macrophages. Moreover, we also showed that the pharmacological
      effects of F215 were restricted to the local inflamed skin elicited by 12-o
      tetradecanoylphorbol-13-acetate (TPA), but not the normal tissues. We believe
      that F215 could be a useful probe to investigate the function of NAAA, as well as
      a potent anti-inflammatory agent, and its inflammation-restricted feature might
      offer a new approach to prevent potential side effects of systemic enzyme
      inhibition.

PMID- 29572191
TI  - High Right Atrial Pressure and Low Pulse Pressure Predict Gastrointestinal
      Bleeding in Patients With Left Ventricular Assist Device.
AB  - BACKGROUND: Gastrointestinal bleeding (GIB) remains a major morbid event during
      continuous flow left ventricular assist device (LVAD) support. This study
      investigated whether a common hemodynamic profile is associated with GIB in
      patients with LVADs. METHODS AND RESULTS: A single institution analysis reviewed
      all patients who underwent right heart catheterization (RHC) following LVAD
      implant between January 1, 2006, and December 31, 2013, with follow-up through
      June 2015. Kaplan-Meier and multiphase hazard statistical methods were employed.
      Among 108 patients with 341 RHC, 55 hospitalizations for GIB occurred within 1
      year of RHC. Freedom from GIB at 6 months was 92% in patients with pulse pressure
      >=35 mmHg, compared with 76% with pulse pressure <35 mmHg. By multivariable
      analysis, the significant predictors of GIB were: older age at implant, number of
      prior GIB, lower pulse pressure, lower mean arterial pressure, and higher right
      atrial pressure (all P < .05). The magnitude of effect is influenced by pulse
      pressure. CONCLUSIONS: Greater pulsatility and less venous congestion, along with
      other factors, are associated with a lower risk for GIB. It is reasonable to
      adjust therapeutic strategies to target this hemodynamic profile in patients with
      a propensity for GIB.

PMID- 29572190
TI  - Incident Hyperkalemia, Hypokalemia, and Clinical Outcomes During Spironolactone
      Treatment of Heart Failure With Preserved Ejection Fraction: Analysis of the
      TOPCAT Trial.
AB  - BACKGROUND: In patients with heart failure and preserved ejection fraction (HF
      PEF) randomized in the Americas as part of the Treatment of Preserved Cardiac
      Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, treatment
      with spironolactone enhanced the risk of hyperkalemia but reduced the risk of
      hypokalemia. We examined the clinical correlates and prognostic implications of
      incident hypo- and hyperkalemia during study follow-up. METHODS: We defined the
      region-specific incidence of hypokalemia (potassium [K+] <3.5 mmol/l) and
      hyperkalemia (K+ >=5.5 mmol/l) among both placebo- and spironolactone-assigned
      patients in TOPCAT. Factors associated with incident hypokalemia and hyperkalemia
      and the relationship between incident K+ abnormalities and the risk of subsequent
      mortality were analyzed in multivariable regression models restricted to the
      Americas. RESULTS: In the Americas, assignment to spironolactone increased risk
      for hyperkalemia (hazard ratio 3.21, 95% confidence interval 2.46-4.20, P < .001)
      and reduced risk of hypokalemia (hazard ratio 0.43, 95% confidence interval 0.34
      0.55, P < .001). Assignment to spironolactone, lower estimated glomerular
      filtration rate, higher baseline K+, diabetes, and lower hemoglobin were
      associated with incident hyperkalemia, whereas assignment to placebo, lower K+,
      younger age, lower estimated glomerular filtration rate, and use of diuretics at
      baseline were associated with hypokalemia. The combination of spironolactone and
      an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was
      associated with incremental risk for hyperkalemia and protection from
      hypokalemia. Independent of region, both hypokalemia and hyperkalemia, were
      associated with higher risk for cardiovascular and all-cause mortality in
      multivariable-adjusted Cox regression models. CONCLUSIONS: Both hyperkalemia and
      hypokalemia are associated with heightened risk for mortality in HF-PEF. Use of
      spironolactone in this population requires careful laboratory surveillance of K+
      and creatinine, particularly in high-risk groups.

PMID- 29572192
TI  - Omalizumab for the Treatment of Solar Urticaria: Case Series and Systematic
      Review of the Literature.
AB  - BACKGROUND: Solar urticaria (SU) is a rare photodermatosis causing a significant
      impact on patients' quality of life. Although the condition can be controlled
      with phototherapy and/or a combination therapy of antihistamines and leukotriene
      antagonist in most patients, a subset of patients require additional therapy with
      omalizumab; however, efficacy data are sparse. OBJECTIVE: The objective of this
      study was to determine the efficacy and safety of omalizumab for treating SU.
      METHODS: A case series of 5 patients with SU refractory to antihistamine and
      leukotriene antagonist combination who were treated with omalizumab is described.
      In addition, a systematic review of studies evaluating patients with SU treated
      with omalizumab was conducted. The primary outcome was partial/complete clinical
      response. Secondary outcomes were 10-fold decreases in the baseline minimal
      urticarial dose and adverse events. RESULTS: Our case series included 5 patients
      with SU. Monthly omalizumab doses of 150 to 600 mg resulted in clinical
      improvement in all patients and complete remission in 4. No adverse effects were
      reported. The systematic review included 22 studies (48 patients). All patients
      failed to control disease with antihistamines before omalizumab treatment.
      Patients received omalizumab at monthly doses of 150 to 750 mg over a follow-up
      period of 4 to 200 weeks. Thirty-eight patients (79%) experienced clinical
      improvement. Four patients (11%) had mild adverse effects. CONCLUSIONS:
      Omalizumab provided clinical benefits in approximately 80% of patients with SU.
      Patients failing to improve on standard omalizumab doses may benefit from higher
      monthly dosages.

PMID- 29572193
TI  - CD36 gene variants is associated with type 2 diabetes mellitus through the
      interaction of obesity in rural Chinese adults.
AB  - BACKGROUND: Evidences show that cluster determinant 36 (CD36) protein plays a
      role in lipid metabolism and insulin resistance, and the expression of CD36 is
      inducible in obesity. The present study evaluated the association of CD36
      variants and the interaction with obesity on type 2 diabetes mellitus (T2DM)
      risk. METHODS: We performed a case-control study nested in the Rural Chinese
      Cohort Study. We included 546 incident T2DM cases matched with non-T2DM controls
      in a 1:1 ratio by sex, age (within 2 years), marital status, and residence
      village. Four loci in CD36 (rs1194197, rs2151916, rs3211956, and rs7755) were
      genotyped by SNPscanTM Genotyping system. RESULTS: After adjusting for potential
      confounding, we observed no statistically significant association between the
      CD36 polymorphisms and T2DM risk. Compared to wild-type homozygous carriers with
      normal weight, overweight/obesity participants carrying the mutational allele
      rs7755 showed increased risk of T2DM, by 114% (OR = 2.14, 95% CI: 1.33-3.46;
      Pinteraction = 0.007); abdominal obesity participants carrying the mutational
      allele rs7755 showed increased risk of T2DM, by 133% (OR = 2.33, 95% CI: 1.48
      3.66; Pinteraction = 0.002). Furthermore, rs2151916 polymorphism was associated
      with triglycerides level (P = 0.019), and the rs1194197 variant was related to
      systolic blood pressure (P = 0.023) within the group of controls. CONCLUSIONS:
      CD36 genotypes were not associated with the progression to T2DM independently.
      However, our results suggested a positive interaction between the CD36 variants
      and obesity on T2DM susceptibility, which might be through a cardiometabolic
      disorder.

PMID- 29572194
TI  - Genetic differentiation and forensic efficiency evaluation for Chinese Salar
      ethnic minority based on a 5-dye multiplex insertion and deletion panel.
AB  - The present study investigated the genetic diversities of 30 autosomal insertion
      and deletion (InDel) loci of Investigator DIPplex kit (Qiagen) in Chinese Salar
      ethnic minority and explored the genetic relationships between the studied Salar
      group and other populations. The allelic frequencies of deletion alleles at the
      30 InDel loci were in the range of 0.1739 (HLD64) to 0.8478 (HLD39). The
      discrimination power, polymorphism information content and probability of
      exclusion ranged from 0.4101 (HLD39) to 0.6447 (HLD136), 0.2247 (HLD39) to 0.3750
      (HLD92) and 0.0400 (HLD39) to 0.2806 (HLD92), respectively. The observed and
      expected heterozygosity were in the range of 0.2348 (HLD39) to 0.5913 (HLD92),
      and 0.2580 (HLD39) to 0.5000 (HLD92), respectively. The cumulative discrimination
      power and probability of exclusion of the 30 loci reached 0.999999999993418 and
      0.99039, respectively. The results of population genetic differentiation
      comparisons revealed that Salar group had similar allele distributions with
      Qinghai Tibetan, Xibe and Yi groups. Population Bayesian cluster analysis showed
      that there were similar ancestry components between Salar group and most Chinese
      populations. Besides, the principal components analysis and phylogenetic
      reconstructions further indicated that Salar group had intimate genetic
      relationships with Qinghai Tibetan and Xibe groups. In short, the results of the
      current studies indicated the genetic distributions of the 30 InDel loci in Salar
      group were relatively high genetic polymorphisms, which could be used in forensic
      individual identifications and as a supplementary tool for complex paternity
      testing.

PMID- 29572195
TI  - Biallelic UNC80 mutations caused infantile hypotonia with psychomotor retardation
      and characteristic facies 2 in two Chinese patients with variable phenotypes.
AB  - Biallelic UNC80 mutations cause infantile hypotonia with psychomotor retardation
      and characteristic facies 2 (IHPRF2), which is characterized by hypotonia,
      developmental delay (DD)/intellectual disability (ID), intrauterine growth
      retardation, postnatal growth retardation and characteristic facial features. We
      report two unrelated Chinese patients with compound heterozygous UNC80 mutations
      inherited from their parents, as identified by whole-exome sequencing (WES).
      Mutations c.3719G>A (p.W1240*)/c.4926_4937del (p.N1643_L1646del) and c.4963C>T
      (p.R1655C)/c.8385C>G (p.Y2795*) were identified in patient 1 and patient 2,
      respectively. Although both patients presented with DD/ID and hypotonia,
      different manifestations also occurred. Patient 1 presented with infantile
      hypotonia, epilepsy and hyperactivity without growth retardation, whereas patient
      2 presented with persistent hypotonia, growth retardation and self-injury without
      epilepsy. Furthermore, we herein summarize the genotypes and phenotypes of
      patients with UNC80 mutations reported in the literature, revealing that IHPRF2
      is a phenotypically heterogeneous disease. Common facial dysmorphisms include a
      thin upper lip, a tented upper lip, a triangular face, strabismus and
      microcephaly. To some extent, the manifestations of IHPRF2 mimic those of
      Angelman syndrome (AS)-like syndromes.

PMID- 29572196
TI  - Familial Hypertrophic Cardiomyopathy - Identification of cause and risk
      stratification through exome sequencing.
AB  - BACKGROUND: Hypertrophic Cardiomyopathy (HCM) with variable clinical
      presentations and heterogeneity is the common cause of sudden cardiac death.
      Genetic diagnosis is challenging in these complex diseases but exome sequencing
      as a genetic diagnostic tool provides explainable results. METHODS: In a familial
      Hypertrophic Cardiomyopathy with multigenerational inheritance with apparent
      phenotype, had a history of sudden death and severe arrhythmia followed by
      implantation of Implantable cardioverter defibrillator (ICD). Exome sequencing
      (100*) trailed by effective filtering steps for exome variants on the basis of
      different parameters, segregated variants are prioritized for the disease and
      further clinical relevance are evaluated for the variants. RESULTS: A rare causal
      variant in troponin-T gene (TNNT2, NM_000364.3;c.274C > T;p.Arg92Trp) is
      identified, shared by only affected members, absent in unaffected members and
      also in 200 unrelated control chromosomes. TNNT2 mutation act as a driver
      mutation but mutations in other disease-related genes, KCNMB1, LPL, APOE and
      other biochemical factors provides risk stratification within affected family
      members. CONCLUSION: This study contributes to the role of "rare variants" in
      complex disease phenotypes and heterogeneity within family and the necessity of
      whole exome targeted approaches in complex cardiomyopathy, which are known to
      harbor private mutations.

PMID- 29572198
TI  - Hepatitis B Virus Covalently Closed Circular DNA-Selective Droplet Digital PCR: A
      Sensitive and Noninvasive Method for Hepatocellular Carcinoma Diagnosis?
AB  - This commentary highlights the article by Huang et al that reports a highly
      sensitive assay for detection of closed circular DNA of hepatitis B virus.

PMID- 29572197
TI  - NOD2 expression, DNA damage and oxido-inflammatory status in atopic bronchial
      asthma: Exploring their nexus to disease severity.
AB  - BACKGROUND: Allergic asthma is a chronically relapsing inflammatory airway
      disease with a complex pathophysiology. AIM: This study was undertaken to
      investigate the potential contribution of NOD2 signaling, proinflammatory
      cytokines, chitotriosidase (CHIT1) activity, oxidative stress and DNA damage to
      atopic asthma pathogenesis, as well as to explore their possible role as
      surrogate noninvasive biomarkers for monitoring asthma severity. METHODS: Sixty
      patients with atopic bronchial asthma who were divided according to asthma
      severity into 40 mild-moderate, 20 severe atopic asthmatics, in addition to
      thirty age-matched healthy controls were enrolled in this study. NOD2 expression
      in PBMCs was assessed by quantitative real-time RT-PCR. DNA damage indices were
      assessed by alkaline comet assay. Serum IgE, IL-17, IL-8 and 3-Nitrotyrosine
      levels were estimated by ELISA. Serum CHIT1and GST activities, as well as MDA
      levels, were measured. RESULTS: NOD2 mRNA relative expression levels were
      significantly decreased in atopic asthmatic cases relative to controls with lower
      values among severe atopic asthmatics. On the other hand, IL-17 and IL-8 serum
      levels, CHIT1 activity, DNA damage indices and oxidative stress markers were
      significantly increased in atopic asthmatic cases relative to controls with
      higher values among severe atopic asthmatics. The change in these parameters
      correlated significantly with the degree of decline in lung function. CONCLUSION:
      The interplay between NOD2 signaling, proinflammatory cytokines, CHIT1 activity,
      heightened oxidative stress and DNA damage orchestrates allergic airway
      inflammation and thus contributing to the pathogenesis of atopic asthma. These
      parameters qualified for measurement as part of new noninvasive biomarker panels
      for monitoring asthma severity.

PMID- 29572199
TI  - Assessing the Readability of Medical Documents: A Ranking Approach.
AB  - BACKGROUND: The use of electronic health record (EHR) systems with patient
      engagement capabilities, including viewing, downloading, and transmitting health
      information, has recently grown tremendously. However, using these resources to
      engage patients in managing their own health remains challenging due to the
      complex and technical nature of the EHR narratives. OBJECTIVE: Our objective was
      to develop a machine learning-based system to assess readability levels of
      complex documents such as EHR notes. METHODS: We collected difficulty ratings of
      EHR notes and Wikipedia articles using crowdsourcing from 90 readers. We built a
      supervised model to assess readability based on relative orders of text
      difficulty using both surface text features and word embeddings. We evaluated
      system performance using the Kendall coefficient of concordance against human
      ratings. RESULTS: Our system achieved significantly higher concordance (.734)
      with human annotators than did a baseline using the Flesch-Kincaid Grade Level, a
      widely adopted readability formula (.531). The improvement was also consistent
      across different disease topics. This method's concordance with an individual
      human user's ratings was also higher than the concordance between different human
      annotators (.658). CONCLUSIONS: We explored methods to automatically assess the
      readability levels of clinical narratives. Our ranking-based system using simple
      textual features and easy-to-learn word embeddings outperformed a widely used
      readability formula. Our ranking-based method can predict relative difficulties
      of medical documents. It is not constrained to a predefined set of readability
      levels, a common design in many machine learning-based systems. Furthermore, the
      feature set does not rely on complex processing of the documents. One potential
      application of our readability ranking is personalization, allowing patients to
      better accommodate their own background knowledge.

PMID- 29572201
TI  - Investigating the Impact of Hearing Aid Use and Auditory Training on Cognition,
      Depressive Symptoms, and Social Interaction in Adults With Hearing Loss: Protocol
      for a Crossover Trial.
AB  - BACKGROUND: Sensorineural hearing loss is the most common sensory deficit among
      older adults. Some of the psychosocial consequences of this condition include
      difficulty in understanding speech, depression, and social isolation. Studies
      have shown that older adults with hearing loss show some age-related cognitive
      decline. Hearing aids have been proven as successful interventions to alleviate
      sensorineural hearing loss. In addition to hearing aid use, the positive effects
      of auditory training-formal listening activities designed to optimize speech
      perception-are now being documented among adults with hearing loss who use
      hearing aids, especially new hearing aid users. Auditory training has also been
      shown to produce prolonged cognitive performance improvements. However, there is
      still little evidence to support the benefits of simultaneous hearing aid use and
      individualized face-to-face auditory training on cognitive performance in adults
      with hearing loss. OBJECTIVE: This study will investigate whether using hearing
      aids for the first time will improve the impact of individualized face-to-face
      auditory training on cognition, depression, and social interaction for adults
      with sensorineural hearing loss. The rationale for this study is based on the
      hypothesis that, in adults with sensorineural hearing loss, using hearing aids
      for the first time in combination with individualized face-to-face auditory
      training will be more effective for improving cognition, depressive symptoms, and
      social interaction rather than auditory training on its own. METHODS: This is a
      crossover trial targeting 40 men and women between 50 and 90 years of age with
      either mild or moderate symmetric sensorineural hearing loss. Consented, willing
      participants will be recruited from either an independent living accommodation or
      via a community database to undergo a 6-month intensive face-to-face auditory
      training program (active control). Participants will be assigned in random order
      to receive hearing aid (intervention) for either the first 3 or last 3 months of
      the 6-month auditory training program. Each participant will be tested at
      baseline, 3, and 6 months using a neuropsychological battery of computer-based
      cognitive assessments, together with a depression symptom instrument and a social
      interaction measure. The primary outcome will be cognitive performance with
      regard to spatial working memory. Secondary outcome measures include other
      cognition performance measures, depressive symptoms, social interaction, and
      hearing satisfaction. RESULTS: Data analysis is currently under way and the first
      results are expected to be submitted for publication in June 2018. CONCLUSIONS:
      Results from the study will inform strategies for aural rehabilitation, hearing
      aid delivery, and future hearing loss intervention trials. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03112850; https://clinicaltrials.gov/ct2/show/NCT03112850
      (Archived by WebCite at http://www.webcitation.org/6xz12fD0B).

PMID- 29572200
TI  - Evaluating the Impact of Physical Activity Apps and Wearables: Interdisciplinary
      Review.
AB  - BACKGROUND: Although many smartphone apps and wearables have been designed to
      improve physical activity, their rapidly evolving nature and complexity present
      challenges for evaluating their impact. Traditional methodologies, such as
      randomized controlled trials (RCTs), can be slow. To keep pace with rapid
      technological development, evaluations of mobile health technologies must be
      efficient. Rapid alternative research designs have been proposed, and efficient
      in-app data collection methods, including in-device sensors and device-generated
      logs, are available. Along with effectiveness, it is important to measure
      engagement (ie, users' interaction and usage behavior) and acceptability (ie,
      users' subjective perceptions and experiences) to help explain how and why apps
      and wearables work. OBJECTIVES: This study aimed to (1) explore the extent to
      which evaluations of physical activity apps and wearables: employ rapid research
      designs; assess engagement, acceptability, as well as effectiveness; use
      efficient data collection methods; and (2) describe which dimensions of
      engagement and acceptability are assessed. METHOD: An interdisciplinary scoping
      review using 8 databases from health and computing sciences. Included studies
      measured physical activity, and evaluated physical activity apps or wearables
      that provided sensor-based feedback. Results were analyzed using descriptive
      numerical summaries, chi-square testing, and qualitative thematic analysis.
      RESULTS: A total of 1829 abstracts were screened, and 858 articles read in full.
      Of 111 included studies, 61 (55.0%) were published between 2015 and 2017. Most
      (55.0%, 61/111) were RCTs, and only 2 studies (1.8%) used rapid research designs:
      1 single-case design and 1 multiphase optimization strategy. Other research
      designs included 23 (22.5%) repeated measures designs, 11 (9.9%) nonrandomized
      group designs, 10 (9.0%) case studies, and 4 (3.6%) observational studies. Less
      than one-third of the studies (32.0%, 35/111) investigated effectiveness,
      engagement, and acceptability together. To measure physical activity, most
      studies (90.1%, 101/111) employed sensors (either in-device [67.6%, 75/111] or
      external [23.4%, 26/111]). RCTs were more likely to employ external sensors
      (accelerometers: P=.005). Studies that assessed engagement (52.3%, 58/111) mostly
      used device-generated logs (91%, 53/58) to measure the frequency, depth, and
      length of engagement. Studies that assessed acceptability (57.7%, 64/111) most
      often used questionnaires (64%, 42/64) and/or qualitative methods (53%, 34/64) to
      explore appreciation, perceived effectiveness and usefulness, satisfaction,
      intention to continue use, and social acceptability. Some studies (14.4%, 16/111)
      assessed dimensions more closely related to usability (ie, burden of sensor wear
      and use, interface complexity, and perceived technical performance). CONCLUSIONS:
      The rapid increase of research into the impact of physical activity apps and
      wearables means that evaluation guidelines are urgently needed to promote
      efficiency through the use of rapid research designs, in-device sensors and user
      logs to assess effectiveness, engagement, and acceptability. Screening articles
      was time-consuming because reporting across health and computing sciences lacked
      standardization. Reporting guidelines are therefore needed to facilitate the
      synthesis of evidence across disciplines.

PMID- 29572202
TI  - Influence of Flavors on the Propagation of E-Cigarette-Related Information:
      Social Media Study.
AB  - BACKGROUND: Modeling the influence of e-cigarette flavors on information
      propagation could provide quantitative policy decision support concerning smoking
      initiation and contagion, as well as e-cigarette regulations. OBJECTIVE: The
      objective of this study was to characterize the influence of flavors on e
      cigarette-related information propagation on social media. METHODS: We collected
      a comprehensive dataset of e-cigarette-related discussions from public Pages on
      Facebook. We identified 11 categories of flavors based on commonly used
      categorizations. Each post's frequency of being shared served as a proxy measure
      of information propagation. We evaluated a set of regression models and chose the
      hurdle negative binomial model to characterize the influence of different flavors
      and nonflavor control variables on e-cigarette-related information propagation.
      RESULTS: We found that 5 flavors (sweet, dessert & bakery, fruits, herbs &
      spices, and tobacco) had significantly negative influences on e-cigarette-related
      information propagation, indicating the users' tendency not to share posts
      related to these flavors. We did not find a positive significance of any flavors,
      which is contradictory to previous research. In addition, we found that a set of
      nonflavor-related factors were associated with information propagation.
      CONCLUSIONS: Mentions of flavors in posts did not enhance the popularity of e
      cigarette-related information. Certain flavors could even have reduced the
      popularity of information, indicating users' lack of interest in flavors.
      Promoting e-cigarette-related information with mention of flavors is not an
      effective marketing approach. This study implies the potential concern of users
      about flavorings and suggests a need to regulate the use of flavorings in e
      cigarettes.

PMID- 29572203
TI  - General Practitioners' Attitudes Toward a Web-Based Mental Health Service for
      Adolescents: Implications for Service Design and Delivery.
AB  - BACKGROUND: Anxiety disorders and depression are prevalent among youth. General
      practitioners (GPs) are often the first point of professional contact for
      treating health problems in young people. A Web-based mental health service
      delivered in partnership with schools may facilitate increased access to
      psychological care among adolescents. However, for such a model to be implemented
      successfully, GPs' views need to be measured. OBJECTIVE: This study aimed to
      examine the needs and attitudes of GPs toward a Web-based mental health service
      for adolescents, and to identify the factors that may affect the provision of
      this type of service and likelihood of integration. Findings will inform the
      content and overall service design. METHODS: GPs were interviewed individually
      about the proposed Web-based service. Qualitative analysis of transcripts was
      performed using thematic coding. A short follow-up questionnaire was delivered to
      assess background characteristics, level of acceptability, and likelihood of
      integration of the Web-based mental health service. RESULTS: A total of 13 GPs
      participated in the interview and 11 completed a follow-up online questionnaire.
      Findings suggest strong support for the proposed Web-based mental health service.
      A wide range of factors were found to influence the likelihood of GPs integrating
      a Web-based service into their clinical practice. Coordinated collaboration with
      parents, students, school counselors, and other mental health care professionals
      were considered important by nearly all GPs. Confidence in Web-based care,
      noncompliance of adolescents and GPs, accessibility, privacy, and confidentiality
      were identified as potential barriers to adopting the proposed Web-based service.
      CONCLUSIONS: GPs were open to a proposed Web-based service for the monitoring and
      management of anxiety and depression in adolescents, provided that a
      collaborative approach to care is used, the feedback regarding the client is
      clear, and privacy and security provisions are assured.

PMID- 29572204
TI  - Rapid and Accurate Behavioral Health Diagnostic Screening: Initial Validation
      Study of a Web-Based, Self-Report Tool (the SAGE-SR).
AB  - BACKGROUND: The Structured Clinical Interview for DSM (SCID) is considered the
      gold standard assessment for accurate, reliable psychiatric diagnoses; however,
      because of its length, complexity, and training required, the SCID is rarely used
      outside of research. OBJECTIVE: This paper aims to describe the development and
      initial validation of a Web-based, self-report screening instrument (the
      Screening Assessment for Guiding Evaluation-Self-Report, SAGE-SR) based on the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and
      the SCID-5-Clinician Version (CV) intended to make accurate, broad-based
      behavioral health diagnostic screening more accessible within clinical care.
      METHODS: First, study staff drafted approximately 1200 self-report items
      representing individual granular symptoms in the diagnostic criteria for the 8
      primary SCID-CV modules. An expert panel iteratively reviewed, critiqued, and
      revised items. The resulting items were iteratively administered and revised
      through 3 rounds of cognitive interviewing with community mental health center
      participants. In the first 2 rounds, the SCID was also administered to
      participants to directly compare their Likert self-report and SCID responses. A
      second expert panel evaluated the final pool of items from cognitive interviewing
      and criteria in the DSM-5 to construct the SAGE-SR, a computerized adaptive
      instrument that uses branching logic from a screener section to administer
      appropriate follow-up questions to refine the differential diagnoses. The SAGE-SR
      was administered to healthy controls and outpatient mental health clinic clients
      to assess test duration and test-retest reliability. Cutoff scores for screening
      into follow-up diagnostic sections and criteria for inclusion of diagnoses in the
      differential diagnosis were evaluated. RESULTS: The expert panel reduced the
      initial 1200 test items to 664 items that panel members agreed collectively
      represented the SCID items from the 8 targeted modules and DSM criteria for the
      covered diagnoses. These 664 items were iteratively submitted to 3 rounds of
      cognitive interviewing with 50 community mental health center participants; the
      expert panel reviewed session summaries and agreed on a final set of 661 clear
      and concise self-report items representing the desired criteria in the DSM-5. The
      SAGE-SR constructed from this item pool took an average of 14 min to complete in
      a nonclinical sample versus 24 min in a clinical sample. Responses to individual
      items can be combined to generate DSM criteria endorsements and differential
      diagnoses, as well as provide indices of individual symptom severity. Preliminary
      measures of test-retest reliability in a small, nonclinical sample were
      promising, with good to excellent reliability for screener items in 11 of 13
      diagnostic screening modules (intraclass correlation coefficient [ICC] or kappa
      coefficients ranging from .60 to .90), with mania achieving fair test-retest
      reliability (ICC=.50) and other substance use endorsed too infrequently for
      analysis. CONCLUSIONS: The SAGE-SR is a computerized adaptive self-report
      instrument designed to provide rigorous differential diagnostic information to
      clinicians.

PMID- 29572205
TI  - Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a
      Prospective Cohort of US Women.
AB  - BACKGROUND: Circulating branched-chain amino acids (BCAAs; isoleucine, leucine,
      and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their
      association with cardiovascular disease (CVD) is uncertain. We hypothesized that
      plasma BCAAs are positively associated with CVD risk and evaluated whether this
      was dependent on an intermediate diagnosis of T2D. METHODS: Participants in the
      Women's Health Study prospective cohort were eligible if free of CVD at baseline
      blood collection (n=27 041). Plasma metabolites were measured via nuclear
      magnetic resonance spectroscopy. Multivariable Cox regression models estimated
      hazard ratios (HRs) and 95% confidence intervals (CIs) for BCAAs with incident
      CVD (myocardial infarction, stroke, and coronary revascularization). RESULTS: We
      confirmed 2207 CVD events over a mean 18.6 years of follow-up. Adjusting for age,
      body mass index, and other established CVD risk factors, total BCAAs were
      positively associated with CVD (per SD: HR, 1.13; 95% CI, 1.08-1.18), comparable
      to LDL-C (low-density lipoprotein cholesterol) with CVD (per SD: HR, 1.12; 95%
      CI, 1.07-1.17). BCAAs were associated with coronary events (myocardial
      infarction: HR, 1.16; 95% CI, 1.06-1.26; revascularization: HR, 1.17; 95% CI,
      1.11-1.25), and borderline significant association with stroke (HR, 1.07; 95% CI,
      0.99-1.15). The BCAA-CVD association was greater (P interaction=0.036) among
      women who developed T2D before CVD (HR, 1.20; 95% CI, 1.08-1.32) versus women
      without T2D (HR, 1.08; 95% CI, 1.03-1.14). Adjusting for LDL-C, an established
      CVD risk factor, did not attenuate these findings; however, adjusting for HbA1c
      and insulin resistance eliminated the associations of BCAAs with CVD.
      CONCLUSIONS: Circulating plasma BCAAs were positively associated with incident
      CVD in women. Impaired BCAA metabolism may capture the long-term risk of the
      common cause underlying T2D and CVD.

PMID- 29572206
TI  - Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury:
      Implications for Superficial Erosion.
AB  - RATIONALE: Neutrophils likely contribute to the thrombotic complications of human
      atheromata. In particular, neutrophil extracellular traps (NETs) could exacerbate
      local inflammation and amplify and propagate arterial intimal injury and
      thrombosis. PAD4 (peptidyl arginine deiminase 4) participates in NET formation,
      but an understanding of this enzyme's role in atherothrombosis remains scant.
      OBJECTIVE: This study tested the hypothesis that PAD4 and NETs influence
      experimental atherogenesis and in processes implicated in superficial erosion, a
      form of plaque complication we previously associated with NETs. METHODS AND
      RESULTS: Bone marrow chimeric Ldlr deficient mice reconstituted with either wild
      type or PAD4-deficient cells underwent studies that assessed atheroma formation
      or procedures designed to probe mechanisms related to superficial erosion. PAD4
      deficiency neither retarded fatty streak formation nor reduced plaque size or
      inflammation in bone marrow chimeric mice that consumed an atherogenic diet. In
      contrast, either a PAD4 deficiency in bone marrow-derived cells or administration
      of DNaseI to disrupt NETs decreased the extent of arterial intimal injury in mice
      with arterial lesions tailored to recapitulate characteristics of human atheroma
      complicated by erosion. CONCLUSIONS: These results indicate that PAD4 from bone
      marrow-derived cells and NETs do not influence chronic experimental
      atherogenesis, but participate causally in acute thrombotic complications of
      intimal lesions that recapitulate features of superficial erosion.

PMID- 29572207
TI  - Cross-talk between nitric oxide and calcium-calmodulin regulate ganoderic acid
      biosynthesis in Ganoderma lucidum under heat stress.
AB  - We previously reported that high temperature impacts ganoderic acid (GA)
      biosynthesis in Ganoderma lucidum (G. lucidum) via Ca2+ Therefore, to further
      understand the signal regulating network of the organism's response to heat
      stress (HS), we examined the role of nitric oxide (NO) under HS. After HS
      treatment, the NO level was significantly increased by 120% compared with that
      under the control conditions. The application of a NO scavenger resulted in a 25%
      increase in GA compared with that found in the sample treated only with HS.
      Additionally, application of a NO donor to increase NO resulted in a 30% lower GA
      content than that in the sample treated only with HS. These results show that the
      increase in NO alleviates HS-induced GA accumulation. Subsequently, we aimed to
      detect the effects of the interaction between NO and Ca2+ on GA biosynthesis
      under HS in G. lucidum Our pharmacological approaches revealed that the NO and
      Ca2+ signals promoted each other in response to HS. We further constructed the
      silenced strain of nitrate reductase (NR) and calmodulin (CaM), and the results
      are in good agreement with the silenced strain and pharmacological experiment.
      The cross-promotion between NO and Ca2+ signals is involved in the regulation of
      HS-induced GA biosynthesis in G. lucidum, and this finding is supported by
      studies with NRi and CaMi strains. However, Ca2+ may have a more direct and
      significant effects on the HS-induced GA increase than NO. These data indicate
      that NO functions in signaling and has a close relationship with Ca2+ in HS
      induced GA biosynthesis.IMPORTANCE HS is an important environmental stress
      affecting the growth and development of organisms. We previously reported that HS
      modulates GA biosynthesis in G. lucidum via Ca2+ However, the signal regulating
      network of the organism's response to HS has not yet been elucidated. In this
      study, we found that NO relieved HS-induced GA accumulation, and NO and Ca2+
      could exert promoting effects on each other in response to HS. Further research
      on the effect of NO and Ca2+ on the production of GAs in response to HS indicated
      that Ca2+ has a notably more direct and significant effect on the HS-induced GA
      increase than NO. Our results improve our understanding of the mechanism of HS
      signal transduction in fungi. A greater understanding of the regulation of
      secondary metabolism in response to environmental stimuli will provide clues
      regarding the role of these products in fungal biology.

PMID- 29572208
TI  - Induction of Genes Encoding Plant Cell Wall-Degrading Carbohydrate-Active Enzymes
      by Lignocellulose-Derived Monosaccharides and Cellobiose in the White-Rot Fungus
      Dichomitus squalens.
AB  - Fungi can decompose plant biomass into small oligo- and monosaccharides to be
      used as carbon sources. Some of these small molecules may induce metabolic
      pathways and the production of extracellular enzymes targeted for degradation of
      plant cell wall polymers. Despite extensive studies in ascomycete fungi, little
      is known about the nature of inducers for the lignocellulolytic systems of
      basidiomycetes. In this study, we analyzed six sugars known to induce the
      expression of lignocellulolytic genes in ascomycetes for their role as inducers
      in the basidiomycete white-rot fungus Dichomitus squalens using a transcriptomic
      approach. This identified cellobiose and l-rhamnose as the main inducers of
      cellulolytic and pectinolytic genes, respectively, of D. squalens Our results
      also identified differences in gene expression patterns between dikaryotic and
      monokaryotic strains of D. squalens cultivated on plant biomass-derived
      monosaccharides and the disaccharide cellobiose. This suggests that despite
      conservation of the induction between these two genetic forms of D. squalens, the
      fine-tuning in the gene regulation of lignocellulose conversion is differently
      organized in these strains.IMPORTANCE Wood-decomposing basidiomycete fungi have a
      major role in the global carbon cycle and are promising candidates for
      lignocellulosic biorefinery applications. However, information on which
      components trigger enzyme production is currently lacking, which is crucial for
      the efficient use of these fungi in biotechnology. In this study, transcriptomes
      of the white-rot fungus Dichomitus squalens from plant biomass-derived
      monosaccharide and cellobiose cultures were studied to identify compounds that
      induce the expression of genes involved in plant biomass degradation.

PMID- 29572209
TI  - Dynamics in copy numbers of five plasmids of a dairy Lactococcus lactis in dairy
      related conditions including near-zero growth rates.
AB  - Lactic acid bacteria can carry multiple plasmids affecting their performance in
      dairy fermentations. The expression of plasmid-encoded genes and the activity of
      the corresponding proteins is severely affected by changes in the number of
      plasmid copies. We studied the impact of growth rate on dynamics of plasmid copy
      numbers at high growth rates in chemostat cultures and down to near-zero growth
      rates in retentostat cultures. Five plasmids of the dairy strain Lactococcus
      lactis FM03-V1 were selected which varied in size (3 to 39 kb), in replication
      mechanism (theta or rolling-circle) and in putative (dairy-associated) functions.
      Copy numbers ranged from 1.5 to 40.5 and the copy number of theta-type
      replicating plasmids were negatively correlated to the plasmid size. Despite the
      extremely wide range of growth rates (0.0003 h-1 to 0.6 h-1), copy numbers of the
      five plasmids were stable and only slightly increased at near-zero growth rates
      showing that the plasmid replication rate was strictly controlled. One low-copy
      number plasmid, carrying a large exopolysaccharide gene cluster, was
      segregationally unstable during retentostat cultivations reflected in complete
      loss of the plasmid in one of the retentostat cultures. The copy number of the
      five plasmids was also hardly affected by varying the pH value, nutrient
      limitation or presence of citrate (maximum 2.2-fold) signifying the stability in
      copy number of the plasmids.ImportanceLactococcus lactis is extensively used in
      starter cultures for dairy fermentations. Important traits for growth and
      survival of L. lactis in dairy fermentations are encoded by genes located on
      plasmids, such as genes involved in lactose and citrate metabolism, protein
      degradation and oligopeptide uptake and bacteriophage resistance. Because the
      number of plasmid copies could affect the expression of plasmid-encoded genes, it
      is important to know the factors that influence the plasmid copy numbers. We
      monitored plasmid copy numbers of L. lactis at near-zero growth rates,
      characteristic for cheese ripening. Moreover, we analysed the effect of pH,
      nutrient limitation and presence of citrate. This showed that plasmid copy
      numbers were stable giving insight into plasmid copy number dynamics in dairy
      fermentations.

PMID- 29572210
TI  - A Novel Glaesserella sp. Isolated from Pigs with Severe Respiratory Infections
      Has a Mosaic Genome with Virulence Factors Putatively Acquired by Horizontal
      Transfer.
AB  - An unknown member of the family Pasteurellaceae was repeatedly isolated from 20-
      to 24-week-old pigs with severe pulmonary lesions reared on the same farm in
      Victoria, Australia. The etiological diagnosis of the disease was inconclusive.
      The complete genome sequence analysis of one strain, 15-184, revealed some
      phylogenic proximity to Glaesserella (Haemophilus) parasuis, the cause of
      Glasser's disease. However, the sequences of the 16S rRNA and housekeeping genes,
      as well as the average nucleotide identity scores, differed from those of all
      other known species in the family Pasteurellaceae The protein content of 15-184
      was composite, with 60% of coding sequences matching known G. parasuis products,
      while more than 20% had a closer relative in the genera Actinobacillus,
      Mannheimia, Pasteurella, and Bibersteinia Several putative virulence genes absent
      from G. parasuis but present in other Pasteurellaceae were also found, including
      the apxIII RTX toxin gene from Actinobacillus pleuropneumoniae, ABC transporters
      from Actinobacillus minor, and iron transporters from various species. Three
      prophages and one integrative conjugative element were present in the isolate.
      Horizontal gene transfers might explain the mosaic genomic structure and atypical
      metabolic and virulence characteristics of 15-184. This organism has not been
      assigned a taxonomic position in the family, but this study underlines the need
      for a large-scale epidemiological and clinical characterization of this novel
      pathogen in swine populations, as a genomic analysis suggests it could have a
      severe impact on pig health.IMPORTANCE Several species of Pasteurellaceae cause a
      range of significant diseases in pigs. A novel member of this family was recently
      isolated from Australian pigs suffering from severe respiratory infections.
      Comparative whole-genome analyses suggest that this bacterium represents a new
      species, which possesses a number of virulence genes horizontally acquired from a
      diverse range of other Pasteurellaceae While the possible contribution of other
      coinfecting noncultivable agents to the disease has not been ruled out in this
      study, the repertoire of virulence genes found in this organism may nevertheless
      explain some aspects of the associated pathology observed on the farm. The
      prevalence of this novel pathogen within pig populations is currently unknown.
      This finding is of particular importance for the pig industry, as this organism
      can have a serious impact on the health of these animals.

PMID- 29572211
TI  - Homologous Recombination in Core Genomes Facilitates Marine Bacterial Adaptation.
AB  - Acquisition of ecologically relevant genes is common among ocean bacteria, but
      whether it has a major impact on genome evolution in marine environments remains
      unknown. Here, we analyzed the core genomes of 16 phylogenetically diverse and
      ecologically relevant bacterioplankton lineages, each consisting of up to five
      genomes varying at the strain level. Statistical approaches identified from each
      lineage up to ~50 loci showing anomalously high divergence at synonymous sites,
      which is best explained by recombination with distantly related organisms. The
      enriched gene categories in these outlier loci match well with the
      characteristics previously identified as the key phenotypes of these lineages.
      Examples are antibiotic synthesis and detoxification in Phaeobacter inhibens,
      exopolysaccharide production in Alteromonas macleodii, hydrocarbon degradation in
      Marinobacter hydrocarbonoclasticus, and cold adaptation in Pseudoalteromonas
      haloplanktis Intriguingly, the outlier loci feature polysaccharide catabolism in
      Cellulophaga baltica but not in Cellulophaga lytica, consistent with their
      primary habitat preferences in macroalga and beach sands respectively. Likewise,
      analysis of Prochlorococcus showed that photosynthesis related genes listed in
      the outlier loci are only found in high-light adapted ecotype but not in the low
      light adapted ecotype. These observations strongly suggest that recombination
      with distant relatives is a key mechanism driving the ecological diversification
      among marine bacterial lineages.IMPORTANCE Acquisition of new metabolic genes has
      been known as an important mechanism driving bacterial evolution and adaptation
      in the ocean, but acquisition of novel alleles of existing genes and its
      potential ecological role has not been examined. Guided by population genetic
      theories, our genomic analysis showed that divergent allele acquisition is
      prevalent in phylogenetically diverse marine bacterial lineages and that the
      affected loci often encode metabolic functions that underlies the known
      ecological roles of the lineages under study.

PMID- 29572214
TI  - Questions of research misconduct follow Trump's pick for CDC director.

PMID- 29572212
TI  - The Autophagy Gene BcATG8 Regulates the Vegetative Differentiation and
      Pathogenicity of Botrytis cinerea.
AB  - Autophagy is a conserved degradation process that maintains intracellular
      homeostasis to ensure normal cell differentiation and development in eukaryotes.
      ATG8 is one of the key molecular components of the autophagy pathway. In this
      study, we identified and characterized BcATG8, a homologue of Saccharomyces
      cerevisiae (yeast) ATG8 in the necrotrophic plant pathogen Botrytis cinerea Yeast
      complementation experiments demonstrated that BcATG8 can functionally complement
      the defects of the yeast ATG8 null mutant. Direct physical interaction between
      BcAtg8 and BcAtg4 was detected in the yeast two-hybrid system. Subcellular
      localization assays showed that green fluorescent protein-tagged BcAtg8 (GFP
      BcAtg8) localized in the cytoplasm as preautophagosomal structures (PAS) under
      general conditions but mainly accumulated in the lumen of vacuoles in the case of
      autophagy induction. Deletion of BcATG8 (DeltaBcAtg8 mutant) blocked autophagy
      and significantly impaired mycelial growth, conidiation, sclerotial formation,
      and virulence. In addition, the conidia of the DeltaBcAtg8 mutant contained fewer
      lipid droplets (LDs), and quantitative real-time PCR (qRT-PCR) assays revealed
      that the basal expression levels of the LD metabolism-related genes in the mutant
      were significantly different from those in the wild-type (WT) strain. All of
      these phenotypic defects were restored by gene complementation. These results
      indicate that BcATG8 is essential for autophagy to regulate fungal development,
      pathogenesis, and lipid metabolism in B. cinereaIMPORTANCE The gray mold fungus
      Botrytis cinerea is an economically important plant pathogen with a broad host
      range. Although there are fungicides for its control, many classes of fungicides
      have failed due to its genetic plasticity. Exploring the fundamental biology of
      B. cinerea can provide the theoretical basis for sustainable and long-term
      disease management. Autophagy is an intracellular process for degradation and
      recycling of cytosolic materials in eukaryotes and is now known to be vital for
      fungal life. Here, we report studies of the biological role of the autophagy gene
      BcATG8 in B. cinerea The results suggest that autophagy plays a crucial role in
      vegetative differentiation and virulence of B. cinerea.

PMID- 29572213
TI  - Assessment of Passive Traps Combined with High-Throughput Sequencing To Study
      Airborne Fungal Communities.
AB  - Techniques based on high-throughput sequencing (HTS) of environmental DNA have
      provided a new way of studying fungal diversity. However, these techniques suffer
      from a number of methodological biases which may appear at any of the steps
      involved in a metabarcoding study. Air is one of the most important environments
      where fungi can be found, because it is the primary medium of dispersal for many
      species. Looking ahead to future developments, it was decided to test 20
      protocols, including different passive spore traps, spore recovery procedures,
      DNA extraction kits, and barcode loci. HTS was performed with the Illumina MiSeq
      platform targeting two subloci of the fungal internal transcribed spacer.
      Multivariate analysis and generalized linear models showed that the type of
      passive spore trap, the spore recovery procedure, and the barcode all impact the
      description of fungal communities in terms of richness and diversity when
      assessed by HTS metabarcoding. In contrast, DNA extraction kits did not
      significantly impact these results. Although passive traps may be used to
      describe airborne fungal communities, a study using specific real-time PCR and a
      mock community showed that these kinds of traps are affected by environmental
      conditions that may induce losses of biological material, impacting diversity and
      community composition results.IMPORTANCE The advent of high-throughput sequencing
      (HTS) methods, such as those offered by next-generation sequencing (NGS)
      techniques, has opened a new era in the study of fungal diversity in different
      environmental substrates. In this study, we show that an assessment of the
      diversity of airborne fungal communities can reliably be achieved by the use of
      simple and robust passive spore traps. However, a comparison of sample processing
      protocols showed that several methodological biases may impact the results of
      fungal diversity when assessed by metabarcoding. Our data suggest that
      identifying these biases is of paramount importance to enable a correct
      identification and relative quantification of community members.

PMID- 29572215
TI  - Health-related quality of life in congenital heart disease surgery in children
      and young adults: a systematic review and meta-analysis.
AB  - BACKGROUND: As survival improves in the congenital heart disease (CHD)
      population, health-related quality of life (HRQOL) outcomes become increasingly
      important. While surgery improves survival, poor HRQOL occurs postoperatively and
      cardiac-related HRQOL outcomes are rarely reported. OBJECTIVE: To conduct a
      systematic review and meta-analyses of general and cardiac-related HRQOL in CHD
      surgical children and young adults. METHOD: Medline, CINAHL and EMBASE were
      searched. Quantitative designs with a minimum of 80% CHD surgical patients and
      mean age <=18 years compared with healthy controls were included in the review.
      Data were analysed in RevMan V.5.3 using a random effects model. OUTCOME
      MEASURES: General and cardiac-related HRQOL. RESULTS: Studies (n=20) were
      conducted in high-income countries and included 3808 patients plus 2951 parental
      reports of patients. HRQOL was worse in postoperative patients with CHD versus
      healthy controls in all domains with the largest difference seen for physical
      function (standard mean difference (SMD) of -0.56, 95% CI -0.82 to -0.30).
      Cardiac-related HRQOL was worse in complex compared with simple CHD with the
      largest SMD (-0.60, 95% CI -0.80 to -0.40) for symptoms. Heterogeneity ranged
      from 0% to 90%. CONCLUSIONS: CHD surgical patients have substantially worse HRQOL
      compared with age-matched healthy controls. Strategies should focus on improving
      HRQOL in this subgroup. Results may not be applicable to low/middle-income
      countries given the dearth of relevant research.

PMID- 29572216
TI  - Femoral bone lesions accompanying cat-scratch disease.

PMID- 29572217
TI  - Outcomes following prolonged convulsions.

PMID- 29572218
TI  - Parry-Romberg syndrome and morphoea en coup de sabre.

PMID- 29572219
TI  - Diagnosing intralobar pulmonary sequestration.

PMID- 29572221
TI  - Are we giving too much IV fluid?

PMID- 29572220
TI  - Caregiver experiences of racism and child healthcare utilisation: cross-sectional
      analysis from New Zealand.
AB  - OBJECTIVES: Children's exposure to racism via caregiver experience (vicarious
      racism) is associated with poorer health and development. However, the
      relationship with child healthcare utilisation is unknown. We aimed to
      investigate (1) the prevalence of vicarious racism by child ethnicity; (2) the
      association between caregiver experiences of racism and child healthcare
      utilisation; and (3) the contribution of caregiver socioeconomic position and
      psychological distress to this association. DESIGN: Cross-sectional analysis of
      two instances of the New Zealand Health Survey (2006/2007: n=4535 child-primary
      caregiver dyads; 2011/2012: n=4420 dyads). MAIN OUTCOME MEASURES: Children's
      unmet need for healthcare, reporting no usual medical centre and caregiver
      reported dissatisfaction with their child's medical centre. RESULTS: The
      prevalence of reporting 'any' experience of racism was higher among caregivers of
      indigenous Maori and Asian children (30.0% for both groups in 2006/2007) compared
      with European/Other children (14.4% in 2006/2007). Vicarious racism was
      independently associated with unmet need for child's healthcare (OR=2.30, 95% CI
      1.65 to 3.20) and dissatisfaction with their child's medical centre (OR=2.00, 95%
      CI 1.26 to 3.16). Importantly, there was a dose-response relationship between the
      number of reported experiences of racism and child healthcare utilisation (eg,
      unmet need: 1 report of racism, OR=1.89, 95% CI 1.34 to 2.67; 2+ reports of
      racism, OR=3.06, 95% CI 1.27 to 7.37). Adjustment for caregiver psychological
      distress attenuated the association between caregiver experiences of racism and
      child healthcare utilisation. CONCLUSIONS: Vicarious racism is a serious health
      problem in New Zealand disproportionately affecting Maori and Asian children and
      significantly impacting children's healthcare utilisation. Tackling racism may be
      an important means of improving inequities in child healthcare utilisation.

PMID- 29572222
TI  - Neurocognitive outcomes in children following immersion: a long-term study.
AB  - OBJECTIVE: To investigate long-term neurocognitive outcomes after a near-drowning
      incident in children who were deemed neurologically intact on discharge from
      hospital. DESIGN: A prospective cohort study of near-drowning children. SETTING:
      95 drowning and near-drowning admissions, 0-16 years of age, from January 2009 to
      December 2013, to The Children's Hospital at Westmead, Sydney, NSW, Australia.
      PARTICIPANTS: 23 children both met the criteria and had parental consent for the
      study. MAIN OUTCOME MEASURES: Identification of the long-term deficits in
      behaviour, executive function, motor skills, communicative skills and well-being
      over a 5-year period. Assessment was undertaken at 3-6 months, 1 year, 3 years
      and 5 years after near-drowning at clinic visits. Physical developmental
      screening and executive function screening were done using Behavior Rating
      Inventory of Executive Function-Preschool version (BRIEF-P) and BRIEF. RESULT: 95
      drowning and near-drowning episodes occurred during the study period. 10 (11%)
      children died, 28 were admitted to the paediatric intensive care unit and 64
      directly to a ward. 3 children died in emergency department, 7 children had
      severe neurological deficit on discharge from the hospital. 23 were subsequently
      recruited into the study; 5 (22%) of these children had abnormalities in
      behaviour and/or executive function at some during their follow-up. CONCLUSION:
      Children admitted to hospital following a near-drowning event warrant long-term
      follow-up to identify any subtle sequelae which might be amenable to intervention
      to ensure optimal patient outcome.

PMID- 29572223
TI  - Journal retracts article for plagiarism after editorial board members resign in
      protest.

PMID- 29572224
TI  - IL22RA1/STAT3 Signaling Promotes Stemness and Tumorigenicity in Pancreatic
      Cancer.
AB  - Chronic inflammation is a feature of pancreatic cancer, but little is known about
      how immune cells or immune cell-related signals affect pancreatic cancer stemness
      and development. Our previous work showed that IL22/IL22RA1 plays a vital role in
      acute and chronic pancreatitis progression by mediating cross-talk between immune
      cells and acinar cells or stellate cells, respectively. Here, we find IL22RA1 is
      highly but heterogeneously expressed in pancreatic cancer cells, with high
      expression associated with poor prognosis of patients with pancreatic cancer. The
      IL22RA1hi population from pancreatic cancer harbored higher stemness potential
      and tumorigenicity. Notably, IL22 promoted pancreatic cancer stemness via
      IL22RA1/STAT3 signaling, establishing the mechanism of regulation of cancer
      stemness by microenvironmental factors. Moreover, STAT3 was indispensable for the
      maintenance of IL22RA1hi cells. Overall, these findings provide a therapeutic
      strategy for patients with PDAC with high expression of IL22RA1.Significance:
      IL22RA1/STAT3 signaling enhances stemness and tumorigenicity in pancreatic
      cancer. Cancer Res; 78(12); 3293-305. (c)2018 AACR.

PMID- 29572225
TI  - Therapeutic Targeting of Sunitinib-Induced AR Phosphorylation in Renal Cell
      Carcinoma.
AB  - Androgen receptor (AR) plays a crucial role in the development and progression of
      prostate cancer. AR expression has also been reported in other solid tumors,
      including renal cell carcinoma (RCC), but its biological role here remains
      unclear. Through integrative analysis of a reverse phase protein array, we
      discovered increased expression of AR in an RCC patient-derived xenograft model
      of acquired resistance to the receptor tyrosine kinase inhibitor (RTKi)
      sunitinib. AR expression was increased in RCC cell lines with either acquired or
      intrinsic sunitinib resistance in vitro An AR signaling gene array profiler
      indicated elevated levels of AR target genes in sunitinib-resistant cells.
      Sunitinib-induced AR transcriptional activity was associated with increased
      phosphorylation of serine 81 (pS81) on AR. Additionally, AR overexpression
      resulted in acquired sunitinib resistance and the AR antagonist enzalutamide
      induced AR degradation and attenuated AR downstream activity in sunitinib
      resistant cells, also indicated by decreased secretion of human kallikrein 2.
      Enzalutamide-induced AR degradation was rescued by either proteasome inhibition
      or by knockdown of the AR ubiquitin ligase speckle-type POZ protein (SPOP). In
      vivo treatment with enzalutamide and sunitinib demonstrated that this combination
      efficiently induced tumor regression in a RCC model following acquired sunitinib
      resistance. Overall, our results suggest the potential role of AR as a target for
      therapeutic interventions, in combination with RTKi, to overcome drug resistance
      in RCC.Significance: These findings highlight the therapeutic potential of
      targeting the androgen receptor to overcome RCC resistance to receptor tyrosine
      kinase inhibitors. Cancer Res; 78(11); 2886-96. (c)2018 AACR.

PMID- 29572226
TI  - A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three
      Novel Loci Predisposing to Breast Cancer.
AB  - Genome-wide association studies have identified more than 90 susceptibility loci
      for breast cancer. However, the missing heritability is evident, and the
      contributions of coding variants to breast cancer susceptibility have not yet
      been systematically evaluated. Here, we present a large-scale whole-exome
      association study for breast cancer consisting of 24,162 individuals (10,055
      cases and 14,107 controls). In addition to replicating known susceptibility loci
      (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in
      C21orf58 (rs13047478, Pmeta = 4.52 * 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 *
      10-9) and one new noncoding variant at 7q21.11 (P < 5 * 10-8). C21orf58 and
      ZNF526 possessed functional roles in the control of breast cancer cell growth,
      and the two coding variants were found to be the eQTL for several nearby genes.
      rs13047478 was significantly (P < 5.00 * 10-8) associated with the expression of
      genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be
      significantly associated with the expression of genes PAFAH1B3 (P = 8.39 * 10-8)
      and CNFN (P = 3.77 * 10-4) in human blood samples. C21orf58 and ZNF526, together
      with these eQTL genes, were differentially expressed in breast tumors versus
      normal breast. Our study reveals additional loci and novel genes for genetic
      predisposition to breast cancer and highlights a polygenic basis of disease
      development.Significance: Large-scale genetic screening identifies novel missense
      variants and a noncoding variant as predisposing factors for breast cancer.
      Cancer Res; 78(11); 3087-97. (c)2018 AACR.

PMID- 29572227
TI  - Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a
      Mitochondrial Translation Switch.
AB  - Mitochondria regulate cellular bioenergetics and redox states and influence
      multiple signaling pathways required for tumorigenesis. In this study, we
      determined that the mitochondrial translation elongation factor 4 (EF4) is a
      critical component of tumor progression. EF4 was ubiquitous in human tissues with
      localization to the mitochondria (mtEF4) and performed quality control on
      respiratory chain biogenesis. Knockout of mtEF4 induced respiratory chain complex
      defects and apoptosis, while its overexpression stimulated cancer development. In
      multiple cancers, expression of mtEF4 was increased in patient tumor tissues.
      These findings reveal that mtEF4 expression may promote tumorigenesis via an
      imbalance in the regulation of mitochondrial activities and subsequent variation
      of cellular redox. Thus, dysregulated mitochondrial translation may play a vital
      role in the etiology and development of diverse human cancers.Significance:
      Dysregulated mitochondrial translation drives tumor development and progression.
      Cancer Res; 78(11); 2813-24. (c)2018 AACR.

PMID- 29572228
TI  - Transition of Mesenchymal and Epithelial Cancer Cells Depends on alpha1-4
      Galactosyltransferase-Mediated Glycosphingolipids.
AB  - The reversible transitions of cancer cells between epithelial and mesenchymal
      states comprise cellular and molecular processes essential for local tumor growth
      and respective dissemination. We report here that globoside glycosphingolipid
      (GSL) glycosyltransferase-encoding genes are elevated in epithelial cells and
      correlate with characteristic EMT signatures predictive of disease outcome.
      Depletion of globosides through CRISPR-Cas9-mediated deletion of the key enzyme
      A4GALT induces EMT, enhances chemoresistance, and increased CD24low/CD44high
      cells. The cholera toxin-induced mesenchymal-to-epithelial transition occurred
      only in cells with functional A4GALT. Cells undergoing EMT lost E-cadherin
      expression through epigenetic silencing at the promoter region of CDH1 However,
      in DeltaA4GALT cells, demethylation was able to rescue E-cadherin-mediated cell
      cell adhesion only in the presence of exogenous A4GALT. Overall, our data suggest
      another class of biomolecules vital for epithelial cancer cells and for
      maintaining cell integrity and function.Significance: This study highlights the
      essential role of glycosphingolipids in the maintenance of epithelial cancer cell
      properties. Cancer Res; 78(11); 2952-65. (c)2018 AACR.

PMID- 29572230
TI  - Durvalumab May Be Effective in Patients with EGFR+/ALK+ NSCLC.
AB  - PD-L1 blockade with durvalumab achieves responses in patients with EGFR+/ALK+ and
      EGFR-/ALK- NSCLC.

PMID- 29572231
TI  - Checkpoint Inhibitors May Induce Myocarditis.
AB  - Myocarditis is a rare but serious side effect that can occur in patients
      receiving immune checkpoint inhibitors. To better understand the condition,
      researchers analyzed the symptoms, timing, demographics, and treatment outcomes
      for 101 patients who developed it following treatment.

PMID- 29572232
TI  - IL18 Promotes MDSC-Mediated Immunosuppression in Multiple Myeloma.
AB  - IL18 drives bone marrow MDSC function to suppress T-cell activity and accelerate
      multiple myeloma.

PMID- 29572229
TI  - The MDA-9/Syntenin/IGF1R/STAT3 Axis Directs Prostate Cancer Invasion.
AB  - Although prostate cancer is clinically manageable during several stages of
      progression, survival is severely compromised once cells invade and metastasize
      to distant organs. Comprehending the pathobiology of invasion is required for
      developing efficacious targeted therapies against metastasis. Based on
      bioinformatics data, we predicted an association of melanoma differentiation
      associated gene-9 [syntenin, or syndecan binding protein (SDCBP)] in prostate
      cancer progression. Using tissue samples from various Gleason stage prostate
      cancer patients with adjacent normal tissue, a series of normal prostate and
      prostate cancer cell lines (with differing tumorigenic/metastatic properties),
      mda-9/syntenin-manipulated variants (including loss-of-function and gain-of
      function cell lines), and CRISPR/Cas9 stable MDA-9/Syntenin knockout cells, we
      now confirm the relevance of and dependence on MDA-9/syntenin in prostate cancer
      invasion. MDA-9/Syntenin physically interacted with insulin-like growth factor-1
      receptor following treatment with insulin-like growth factor binding protein-2
      (IGFBP2), regulating downstream signaling processes that enabled STAT3
      phosphorylation. This activation enhanced expression of MMP2 and MMP9, two
      established enzymes that positively regulate invasion. In addition, MDA
      9/syntenin-mediated upregulation of proangiogenic factors including IGFBP2, IL6,
      IL8, and VEGFA also facilitated migration of prostate cancer cells. Collectively,
      our results draw attention to MDA-9/Syntenin as a positive regulator of prostate
      cancer metastasis, and the potential application of targeting this molecule to
      inhibit invasion and metastasis in prostate cancer and potentially other
      cancers.Significance: This study provides new mechanistic insight into the
      proinvasive role of MDA-9/Syntenin in prostate cancer and has potential for
      therapeutic application to prevent prostate cancer metastasis. Cancer Res;
      78(11); 2852-63. (c)2018 AACR.

PMID- 29572233
TI  - KDM6A Loss Induces Aggressive Pancreatic Cancer in Mice.
AB  - Loss of the X chromosome-encoded KDM6A aberrantly activates oncogenic
      superenhancers.

PMID- 29572234
TI  - ctDNA Analysis for Cancer? Not So Fast.
AB  - An expert panel has concluded that more research is needed before circulating
      tumor DNA analyses are adopted in clinical care. This finding may slow the use of
      such testing among oncologists, some of whom are already basing treatment
      decisions on the results of these assays.

PMID- 29572235
TI  - Protein Phosphatase 2A Is Essential for B-cell Tumor Redox Homeostasis.
AB  - PP2A mediates a metabolic switch from glycolysis to the PPP in B-cell
      malignancies.

PMID- 29572236
TI  - PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in
      Prostate Cancer Cells.
AB  - We report that PTEN-deficient prostate cancer cells use macropinocytosis to
      survive and proliferate under nutrient stress. PTEN loss increased
      macropinocytosis only in the context of AMPK activation, revealing a general
      requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK
      promotes survival under stress. In prostate cancer cells, albumin uptake did not
      require macropinocytosis, but necrotic cell debris proved a specific
      macropinocytic cargo. Isotopic labeling confirmed that macropinocytosed necrotic
      cell proteins fueled new protein synthesis in prostate cancer cells.
      Supplementation with necrotic debris, but not albumin, also maintained lipid
      stores, suggesting that macropinocytosis can supply nutrients other than amino
      acids. Nontransformed prostatic epithelial cells were not macropinocytic, but
      patient-derived prostate cancer organoids and xenografts and autochthonous
      prostate tumors all exhibited constitutive macropinocytosis, and blocking
      macropinocytosis limited prostate tumor growth. Macropinocytosis of extracellular
      material by prostate cancer cells is a previously unappreciated tumor
      microenvironment interaction that could be targeted therapeutically.Significance:
      As PTEN-deficient prostate cancer cells proliferate in low-nutrient environments
      by scavenging necrotic debris and extracellular protein via macropinocytosis,
      blocking macropinocytosis by inhibiting AMPK, RAC1, or PI3K may have therapeutic
      value, particularly in necrotic tumors and in combination with therapies that
      cause nutrient stress. Cancer Discov; 8(7); 866-83. (c)2018 AACR.See related
      commentary by Commisso and Debnath, p. 800This article is highlighted in the In
      This Issue feature, p. 781.

PMID- 29572237
TI  - The desA and desB genes from Clostridium scindens ATCC 35704 encode steroid-17,20
      desmolase.
AB  - Clostridium scindens is a gut microbe capable of removing the side-chain of
      cortisol, forming 11beta-hydro-xyandrostenedione. A cortisol-inducible operon
      (desABCD) was previously identified in C. scindens ATCC 35704 by RNA-Seq. The
      desC gene was shown to encode a cortisol 20alpha-hydroxysteroid dehydrogenase
      (20alpha-HSDH). The desD encodes a protein annotated as a member of the major
      facilitator family, predicted to function as a cortisol transporter. The desA and
      desB genes are annotated as N-terminal and C-terminal transketolases,
      respectively. We hypothesized that the DesAB forms a complex and has steroid
      17,20-desmolase activity. We cloned the desA and desB genes from C. scindens ATCC
      35704 in pETDuet for overexpression in Escherichia coli The purified recombinant
      DesAB was determined to be a 142 +/- 5.4 kDa heterotetramer. We developed an
      enzyme-linked continuous spectrophotometric assay to quantify steroid-17,20
      desmolase. This was achieved by coupling DesAB-dependent formation of 11beta
      hydroxyandrostenedione with the NADPH-dependent reduction of the steroid 17-keto
      group by a recombinant 17beta-HSDH from the filamentous fungus, Cochliobolus
      lunatus The pH optimum for the coupled assay was 7.0 and kinetic constants using
      cortisol as substrate were Km of 4.96 +/- 0.57 uM and kcat of 0.87 +/- 0.076 min
      1 Substrate-specificity studies revealed that rDesAB recognized substrates
      regardless of 11beta-hydroxylation, but had an absolute requirement for 17,21
      dihydroxy 20-ketosteroids.

PMID- 29572238
TI  - Suppression of diabetes by accumulation of non-islet-specific CD8+ effector T
      cells in pancreatic islets.
AB  - The inflammatory lesion at the pancreatic islet in type 1 diabetes (T1D) contains
      a heterogeneous infiltrate of T cells. In human and mouse studies, a large
      majority (98 to 99%) of the cytotoxic CD8+ T cells (CTLs) within islets are not
      specific to any islet antigen and are thought to passively add to tissue damage.
      We show by intravital confocal microscopy the opposite, immune-regulatory
      function of this cohort of CTLs. Diabetes did not develop in mice with islets
      showing high levels of infiltration of non-islet-specific CTLs not recognizing
      local antigens. Accumulation of such CTLs resulted in lower activation and
      proliferation of islet-specific CTLs, leading them to enter a state of
      unresponsiveness due to limited access to antigens at the inflammatory lesion.
      This nonspecific suppression by nonautoreactive CTLs was recapitulated in a model
      of viral meningitis, may explain viral interference in autoimmunity, and provides
      insight into the regulation of organ-specific autoimmune responses.

PMID- 29572240
TI  - Regulation of macropinocytosis in Dictyostelium.

PMID- 29572239
TI  - Identification of novel MECOM gene fusion and personalized therapeutic targets
      through integrative clinical sequencing in secondary acute myeloid leukemia in a
      patient with severe congenital neutropenia: a case report and literature review.
AB  - Severe congenital neutropenia (SCN) is a rare hematologic disorder characterized
      by defective myelopoiesis and a high incidence of malignant transformation to
      myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). SCN patients who
      develop MDS/AML have excessive toxicities to traditional chemotherapy, and safer
      therapies are needed to improve overall survival in this population. In this
      report, we outline the use of a prospective integrative clinical sequencing trial
      (PEDS-MIONCOSEQ) in a patient with SCN and AML to help identify oncogenic targets
      for less toxic agents. Integrative sequencing identified two somatic cis
      mutations in the colony stimulating factor 3 receptor (CSF3R) gene, a p.T640N
      mutation in the transmembrane region and a p.Q768* truncation mutation in the
      cytoplasmic domain. A somatic mutation p.H105Y, in the runt homology domain (RHD)
      of runt-related transcription factor 1 (RUNX1), was also identified. In addition,
      sequencing discovered a unique in-frame EIF4A2-MECOM (MDS1 and ectopic viral
      integration site 1 complex) chromosomal translocation with high MECOM expression.
      His mutations in CSF3R served as potential targets for tyrosine kinase inhibition
      and therefore provided an avenue to avoid more harmful therapy. This study
      highlights the utility of integrative clinical sequencing in SCN patients who
      develop leukemia and outlines a strategy on how to approach these patients in a
      future clinical sequencing trial to improve historically poor outcomes. A
      thorough review of leukemia in SCN and the role of CSF3R mutations in oncologic
      therapy are provided to support a new strategy on how to approach MDS/AML in SCN.

PMID- 29572242
TI  - Differentiate and switch, a tale of two heads of a lipid.

PMID- 29572241
TI  - Contact-dependent growth inhibition induces high levels of antibiotic-tolerant
      persister cells in clonal bacterial populations.
AB  - Bacterial populations can use bet-hedging strategies to cope with rapidly
      changing environments. One example is non-growing cells in clonal bacterial
      populations that are able to persist antibiotic treatment. Previous studies
      suggest that persisters arise in bacterial populations either stochastically
      through variation in levels of global signalling molecules between individual
      cells, or in response to various stresses. Here, we show that toxins used in
      contact-dependent growth inhibition (CDI) create persisters upon direct contact
      with cells lacking sufficient levels of CdiI immunity protein, which would
      otherwise bind to and neutralize toxin activity. CDI-mediated persisters form
      through a feedforward cycle where the toxic activity of the CdiA toxin increases
      cellular (p)ppGpp levels, which results in Lon-mediated degradation of the
      immunity protein and more free toxin. Thus, CDI systems mediate a population
      density-dependent bet-hedging strategy, where the fraction of non-growing cells
      is increased only when there are many cells of the same genotype. This may be one
      of the mechanisms of how CDI systems increase the fitness of their hosts.

PMID- 29572243
TI  - Fat nerves keep pain at bay.

PMID- 29572244
TI  - Endosome maturation factors Rabenosyn-5/VPS45 and caveolin-1 regulate ciliary
      membrane and polycystin-2 homeostasis.
AB  - Primary cilium structure and function relies on control of ciliary membrane
      homeostasis, regulated by membrane trafficking processes that deliver and
      retrieve ciliary components at the periciliary membrane. However, the molecular
      mechanisms controlling ciliary membrane establishment and maintenance, especially
      in relation to endocytosis, remain poorly understood. Here, using Caenorhabditis
      elegans, we describe closely linked functions for early endosome (EE) maturation
      factors RABS-5 (Rabenosyn-5) and VPS-45 (VPS45) in regulating cilium length and
      morphology, ciliary and periciliary membrane volume, and ciliary signalling
      related sensory behaviour. We demonstrate that RABS-5 and VPS-45 control
      periciliary vesicle number and levels of select EE/endocytic markers (WDFY-2, CAV
      1) and the ciliopathy membrane receptor PKD-2 (polycystin-2). Moreover, we show
      that CAV-1 (caveolin-1) also controls PKD-2 ciliary levels and associated sensory
      behaviour. These data link RABS-5 and VPS-45 ciliary functions to the processing
      of periciliary-derived endocytic vesicles and regulation of ciliary membrane
      homeostasis. Our findings also provide insight into the regulation of PKD-2
      ciliary levels via integrated endosomal sorting and CAV-1-mediated endocytosis.

PMID- 29572245
TI  - A Phase I Trial of the IGF-1R Antibody Ganitumab (AMG 479) in Combination with
      Everolimus (RAD001) and Panitumumab in Patients with Advanced Cancer.
AB  - PURPOSE: This study evaluated the maximum tolerated dose or recommended phase II
      dose (RPTD) and safety and tolerability of the ganitumab and everolimus doublet
      regimen followed by the ganitumab, everolimus, and panitumumab triplet regimen.
      MATERIALS AND METHODS: This was a standard 3 + 3 dose escalation trial. Doublet
      therapy consisted of ganitumab at 12 mg/kg every 2 weeks; doses of everolimus
      were adjusted according to dose-limiting toxicities (DLTs). Panitumumab at 4.8
      mg/kg every 2 weeks was added to the RPTD of ganitumab and everolimus. DLTs were
      assessed in cycle 1; toxicity evaluation was closely monitored throughout
      treatment. Treatment continued until disease progression or undesirable toxicity.
      Pretreatment and on-treatment skin biopsies were collected to assess insulin-like
      growth factor 1 receptor and mammalian target of rapamycin (mTOR) target
      modulation. RESULTS: Forty-three subjects were enrolled. In the doublet regimen,
      two DLTs were observed in cohort 1, no DLTs in cohort -1, and one in cohort -1B.
      The triplet combination was discontinued because of unacceptable toxicity. Common
      adverse events were thrombocytopenia/neutropenia, skin rash, mucositis, fatigue,
      and hyperglycemia. In the doublet regimen, two patients with refractory non-small
      cell lung cancer (NSCLC) achieved prolonged complete responses ranging from 18 to
      >60 months; one treatment-naive patient with chondrosarcoma achieved prolonged
      stable disease >24 months. In dermal granulation tissue, the insulin-like growth
      factor receptor and mTOR pathways were potently and specifically inhibited by
      ganitumab and everolimus, respectively. CONCLUSION: The triplet regimen of
      ganitumab, everolimus, and panitumumab was associated with unacceptable toxicity.
      However, the doublet of ganitumab at 12 mg/kg every 2 weeks and everolimus five
      times weekly had an acceptable safety profile and demonstrated notable clinical
      activity in patients with refractory NSCLC and sarcoma. IMPLICATIONS FOR
      PRACTICE: This trial evaluated the maximum tolerated dose or recommended phase II
      dose and safety and tolerability of the ganitumab and everolimus doublet regimen
      followed by the ganitumab, everolimus, and panitumumab triplet regimen. Although
      the triplet regimen of ganitumab, everolimus, and panitumumab was associated with
      unacceptable toxicity, the doublet of ganitumab at 12 mg/kg every 2 weeks and
      everolimus at five times weekly had an acceptable safety profile and demonstrated
      notable clinical activity in patients with refractory non-small cell lung cancer
      and sarcoma.

PMID- 29572247
TI  - What is the (particulate) matter with biomass fuel use? Indoor air toxicants and
      central haemodynamic burden.

PMID- 29572246
TI  - Comparative Proteomics of Dying and Surviving Cancer Cells Improves the
      Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.
AB  - Chemotherapeutics cause the detachment and death of adherent cancer cells. When
      studying the proteome changes to determine the protein target and mechanism of
      action of anticancer drugs, the still-attached cells are normally used, whereas
      the detached cells are usually ignored. To test the hypothesis that proteomes of
      detached cells contain valuable information, we separately analyzed the proteomes
      of detached and attached HCT-116, A375, and RKO cells treated for 48 h with 5
      fluorouracil, methotrexate and paclitaxel. Individually, the proteomic data on
      attached and detached cells had comparable performance in target and drug
      mechanism deconvolution, whereas the combined data significantly improved the
      target ranking for paclitaxel. Comparative analysis of attached versus detached
      proteomes provided further insight into cell life and death decision making. Six
      proteins consistently up- or downregulated in the detached versus attached cells
      regardless of the drug and cell type were discovered; their role in cell
      death/survival was tested by silencing them with siRNA. Knocking down USP11,
      CTTN, ACAA2, and EIF4H had anti-proliferative effects, affecting UHRF1
      additionally sensitized the cells to the anticancer drugs, while knocking down
      RNF-40 increased cell survival against the treatments. Therefore, adding detached
      cells to the expression proteomics analysis of drug-treated cells can
      significantly increase the analytical value of the approach. The data have been
      deposited to the ProteomeXchange with identifier PXD007686.

PMID- 29572248
TI  - Improving medication adherence in patients with cardiovascular disease: a
      systematic review.
AB  - OBJECTIVE: To evaluate and compare the effect of interventions for improving
      adherence to medications for atherosclerotic cardiovascular disease (ASCVD)
      secondary prevention. METHODS: We extracted eligible trials from a 2014 Cochrane
      systematic review on adherence for any condition. We updated the search from
      CENTRAL, Medline, Embase, PsycINFO, CINAHL, Sociological Abstracts and trial
      registers through November 2016. Study reports needed to be from a randomised
      controlled trial, incorporate participants identified as having ASCVD and
      interventions aimed at improving adherence to medicines for secondary prevention
      of ASCVD and measure both adherence and a clinical outcome. Two reviewers
      independently determined the eligibility of studies, extracted data and conducted
      a narrative synthesis. RESULTS: We identified 17 trials (n=17 448 participants).
      Most trials had high risk of bias in at least one domain. The intervention group
      adherence rates ranged from 44%to99% and the comparator group adherence rates
      ranged from 13% to 96%. Three distinct interventions reported improvements in
      both adherence and clinical outcomes: short message service (65% vs 13% of
      participants with high adherence in the intervention vs control group), a fixed
      dose combination pill (86% vs 65% adherence, risk ratio of being adherent, 1.33;
      95% CI 1.26 to 1.41) and a community health worker-based intervention (97% in the
      intervention group compared with 92% in the control group; OR=2.62, 95% CI 1.32
      to 5.19). CONCLUSIONS: We identified three interventions that demonstrated
      improvements in adherence and clinical outcomes. Ongoing, longer-term trials will
      help determine whether short-term changes in adherence can be maintained and lead
      to differences in clinical events.

PMID- 29572249
TI  - Take home messages with cases from focused update on echocardiographic assessment
      of aortic stenosis.
AB  - Echocardiography plays an important role in the assessment of valvular aortic
      stenosis. Updated recommendations focusing on a stepwise approach to evaluating
      aortic stenosis have recently been published by the European Association of
      Cardiovascular Imaging and the American Society of Echocardiography. This review
      uses illustrative cases to demonstrate technical aspects of aortic stenosis
      assessment and use of the new proposed classification scheme for aortic stenosis.
      Key points from the updated recommendations reviewed in this paper are: (1)
      technical considerations and sources of error in measurement of peak velocity,
      mean aortic valve gradient and aortic valve area by continuity equation. (2)
      Application of flow status using indexed left ventricular stroke volume to
      distinguish patients with low gradients and a low calculated aortic valve area.
      (3) Use of low-dose dobutamine stress echocardiography in patients with low
      ejection fraction. (4) Application of the new classification scheme and review of
      algorithm use for echocardiographic evaluation of severe aortic stenosis.
      Improved understanding of how to handle unmatched variables and adopting an
      integrated approach to determine severity is central to guiding the clinician's
      management of aortic stenosis.

PMID- 29572250
TI  - The role of medical manslaughter must be reconsidered, says leading lawyer.

PMID- 29572251
TI  - Managing dyslipidaemia for the primary prevention of cardiovascular disease.

PMID- 29572252
TI  - Functional and clinical relevance of novel mutations in a large cohort of
      patients with Cockayne syndrome.
AB  - BACKGROUND: Cockayne syndrome (CS) is a rare, autosomal recessive multisystem
      disorder characterised by prenatal or postnatal growth failure, progressive
      neurological dysfunction, ocular and skeletal abnormalities and premature ageing.
      About half of the patients with symptoms diagnostic for CS show cutaneous
      photosensitivity and an abnormal cellular response to UV light due to mutations
      in either the ERCC8/CSA or ERCC6/CSB gene. Studies performed thus far have failed
      to delineate clear genotype-phenotype relationships. We have carried out a four
      centre clinical, molecular and cellular analysis of 124 patients with CS. METHODS
      AND RESULTS: We assigned 39 patients to the ERCC8/CSA and 85 to the ERCC6/CSB
      genes. Most of the genetic variants were truncations. The missense variants were
      distributed non-randomly with concentrations in relatively short regions of the
      respective proteins. Our analyses revealed several hotspots and founder mutations
      in ERCC6/CSB. Although no unequivocal genotype-phenotype relationships could be
      made, patients were more likely to have severe clinical features if the mutation
      was downstream of the PiggyBac insertion in intron 5 of ERCC6/CSB than if it was
      upstream. Also a higher proportion of severely affected patients was found with
      mutations in ERCC6/CSB than in ERCC8/CSA. CONCLUSION: By identifying >70 novel
      homozygous or compound heterozygous genetic variants in 124 patients with CS with
      different disease severity and ethnic backgrounds, we considerably broaden the
      CSA and CSB mutation spectrum responsible for CS. Besides providing information
      relevant for diagnosis of and genetic counselling for this devastating disorder,
      this study improves the definition of the puzzling genotype-phenotype
      relationships in patients with CS.

PMID- 29572253
TI  - Inframe deletion of human ESPN is associated with deafness, vestibulopathy and
      vision impairment.
AB  - BACKGROUND: Usher syndrome (USH) is a neurosensory disorder characterised by
      deafness, variable vestibular areflexia and vision loss. The aim of the study was
      to identify the genetic defect in a Pakistani family (PKDF1051) segregating USH.
      METHODS: Genome-wide linkage analysis was performed by using an Illumina linkage
      array followed by Sanger and exome sequencing. Heterologous cells and mouse organ
      of Corti explant-based transfection assays were used for functional evaluations.
      Detailed clinical evaluations were performed to characterise the USH phenotype.
      RESULTS: Through homozygosity mapping, we genetically linked the USH phenotype
      segregating in family PKDF1051 to markers on chromosome 1p36.32-p36.22. The locus
      was designated USH1M. Using a combination of Sanger sequencing and exome
      sequencing, we identified a novel homozygous 18 base pair inframe deletion in
      ESPN. Variants of ESPN, encoding the actin-bundling protein espin, have been
      previously associated with deafness and vestibular areflexia in humans with no
      apparent visual deficits. Our functional studies in heterologous cells and in
      mouse organ of Corti explant cultures revealed that the six deleted residues in
      affected individuals of family PKDF1051 are essential for the actin bundling
      function of espin demonstrated by ultracentrifugation actin binding and bundling
      assays. Funduscopic examination of the affected individuals of family PKDF1051
      revealed irregular retinal contour, temporal flecks and disc pallor in both eyes.
      ERG revealed diminished rod photoreceptor function among affected individuals.
      CONCLUSION: Our study uncovers an additional USH gene, assigns the USH1 phenotype
      to a variant of ESPN and provides a 12th molecular component to the USH proteome.

PMID- 29572255
TI  - Cardiac Sympathetic Denervation Can Predict the Wearing-off Phenomenon in
      Patients with Parkinson Disease.
AB  - Recent studies have suggested that preserved cardiac sympathetic denervation may
      be associated with a small motor burden in Parkinson disease (PD) and serve as a
      good marker, which is not associated with other nonmotor symptoms. We sought to
      investigate whether cardiac sympathetic denervation increases the risk of the
      early wearing-off phenomenon in PD. Methods: This hospital-based prospective
      study enrolled 266 de novo patients with PD who underwent 123I
      metaiodobenzylguanidine (123I-MIBG) scintigraphy on initial evaluation. The
      patients visited the outpatient clinic every 2-6 mo and were followed for a
      minimum of 18 mo from the time they began taking dopaminergic medication. Each
      patient was assessed for the wearing-off phenomenon on the basis of the clinical
      assessments and symptom diaries. Clinical events were analyzed from the date of
      evaluation by 123I-MIBG scintigraphy until the date of the first occurrence of
      the wearing-off phenomenon, or until the last follow-up date without wearing-off.
      Results: During a mean follow-up period of 30.4 +/- 14.8 mo, 71 patients
      developed wearing-off. The wearing-off phenomenon occurred more in patients with
      decreased 123I-MIBG uptake. A Cox regression analysis revealed that both low 123I
      MIBG uptake and early onset age significantly predicted the development of
      wearing-off. Conclusion: Our study suggests that a reduction in myocardial 123I
      MIBG uptake in PD patients may be associated with a subsequent increased risk for
      the wearing-off phenomenon. Findings strongly support that PD patients with
      normal cardiac sympathetic innervation might have less involvement of the
      midbrain dopaminergic circuitry and a concomitant reduced risk for motor
      complications, such as wearing-off.

PMID- 29572254
TI  - PARP-1-Targeted Radiotherapy in Mouse Models of Glioblastoma.
AB  - The DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is overexpressed in
      glioblastoma, with overall low expression in healthy brain tissue. Paired with
      the availability of specific small molecule inhibitors, PARP-1 is a near-ideal
      target to develop novel radiotherapeutics to induce DNA damage and apoptosis in
      cancer cells, while sparing healthy brain tissue. Methods: We synthesized an 131I
      labeled PARP-1 therapeutic and investigated its pharmacology in vitro and in
      vivo. A subcutaneous tumor model was used to quantify retention times and
      therapeutic efficacy. A potential clinical scenario, intratumoral convection
      enhanced delivery, was mimicked using an orthotopic glioblastoma model combined
      with an implanted osmotic pump system to study local administration of 131I-PARPi
      (PARPi is PARP inhibitor). Results:131I-PARPi is a 1(2H)-phthalazinone, similar
      in structure to the Food and Drug Administration-approved PARP inhibitor AZD
      2281. In vitro studies have shown that 131I-PARPi and AZD-2281 share similar
      pharmacologic profiles. 131I-PARPi delivered 134.1 cGy/MBq intratumoral injected
      activity. Doses to nontarget tissues, including liver and kidney, were
      significantly lower. Radiation damage and cell death in treated tumors were shown
      by p53 activation in U87-MG cells transfected with a p53-bioluminescent reporter.
      Treated mice showed significantly longer survival than mice receiving vehicle (29
      vs. 22 d, P < 0.005) in a subcutaneous model. Convection-enhanced delivery
      demonstrated efficient retention of 131I-PARPi in orthotopic brain tumors, while
      quickly clearing from healthy brain tissue. Conclusion: Our results demonstrate
      131I-PARPi's high potential as a therapeutic and highlight PARP's relevance as a
      target for radionuclide therapy. Radiation plays an integral role in brain tumor
      therapy, and radiolabeled PARP therapeutics could ultimately lead to improvements
      in the standard of care.

PMID- 29572256
TI  - Preclinical Evaluation of Mesothelin-Specific Ligands for SPECT Imaging of Triple
      Negative Breast Cancer.
AB  - Mesothelin is a cell-surface glycoprotein restricted to mesothelial cells
      overexpressed in several types of cancer, including triple-negative breast cancer
      not responding to trastuzumab or hormone-based therapies. Mesothelin-targeting
      therapies are currently being developed. However, the identification of patients
      potentially eligible for such a therapeutic strategy remains challenging. The
      objective of this study was to perform the radiolabeling and preclinical
      evaluation of 99mTc-A1 and 99mTc-C6, two antimesothelin single-domain antibody
      (sdAb)-derived imaging agents. Methods: A1 and C6 were radiolabeled with 99mTc
      and evaluated in vitro on recombinant protein and cells, as well as in vivo in
      xenograft mouse models of the triple-negative breast cancer cell lines HCC70
      (mesothelin-positive) and MDA-MB-231 (mesothelin-negative). Results: Both 99mTc
      A1 and 99mTc-C6 bound mesothelin with high affinity in vitro, with 99mTc-A1
      affinity being 2.4-fold higher than that of 99mTc-C6 (dissociation constant, 43.9
      +/- 4.0 vs. 107 +/- 16 nM, P < 0.05). 99mTc-A1 and 99mTc-C6 remained stable in
      vivo in murine blood (>80% at 2 h) and ex vivo in human blood (>90% at 6 h). In
      vivo 99mTc-A1 uptake (percentage injected dose) in HCC70 tumors was 5-fold higher
      than in MDA-MB-231 tumors and 1.5-fold higher than that of 99mTc-C6 (2.34% +/-
      0.36% vs. 0.48% +/- 0.18% and 1.56% +/- 0.43%, respectively, P < 0.01) and
      resulted in elevated tumor-to-background ratios. In vivo competition experiments
      demonstrated the specificity of 99mTc-A1 uptake in HCC70 tumors. Conclusion:
      Mesothelin-positive tumors were successfully identified by SPECT using 99mTc-A1
      and 99mTc-C6. Considering its superior characteristics, 99mTc-A1 was selected as
      the most suitable tool for further clinical translation.

PMID- 29572257
TI  - SSTR-RADS Version 1.0 as a Reporting System for SSTR PET Imaging and Selection of
      Potential PRRT Candidates: A Proposed Standardization Framework.
AB  - Reliable standards and criteria for somatostatin receptor (SSTR) PET are still
      lacking. We herein propose a structured reporting system on a 5-point scale for
      SSTR PET imaging, titled SSTR-RADS version 1.0, which might serve as a
      standardized assessment for both diagnosis and treatment planning in
      neuroendocrine tumors. SSTR-RADS could guide the imaging specialist in
      interpreting SSTR PET scans, facilitate communication with the referring
      clinician so that appropriate workup for equivocal findings is pursued, and serve
      as a reliable tool for patient selection for planned peptide receptor
      radionuclide therapy.

PMID- 29572258
TI  - Direct Imaging of Drug Distribution and Target Engagement of the PARP Inhibitor
      Rucaparib.
AB  - Poly(ADP-ribose)polymerase (PARP) inhibitors have emerged as potent antitumor
      drugs. Here, we describe the intrinsic fluorescence properties of the clinically
      approved PARP inhibitor rucaparib and its potential to directly measure drug
      distribution and target engagement-a critical factor for understanding drug
      action and improving efficacy. Methods: We characterized the photophysical
      properties of rucaparib and determined its quantum yield and lifetime. Using
      confocal microscopy and flow cytometry, we imaged the intracellular distribution
      of rucaparib and measured uptake and release kinetics. Results: Rucaparib has an
      excitation/emission maximum of 355/480 nm and a quantum yield of 0.3. In vitro
      time-lapse imaging showed accumulation in cell nuclei within seconds of
      administration. Nuclear rucaparib uptake increased with higher PARP1 expression,
      and we determined an intracellular half-life of 6.4 h. Conclusion: The label
      free, intrinsic fluorescence of rucaparib can be exploited to interrogate drug
      distribution and target binding, critical factors toward improving treatment
      efficacy and outcome.

PMID- 29572259
TI  - The cross-tissue metabolic response of abalone (Haliotis midae) to functional
      hypoxia.
AB  - Functional hypoxia is a stress condition caused by the abalone itself as a result
      of increased muscle activity, which generally necessitates the employment of
      anaerobic metabolism if the activity is sustained for prolonged periods. With
      that being said, abalone are highly reliant on anaerobic metabolism to provide
      partial compensation for energy production during oxygen-deprived episodes.
      However, current knowledge on the holistic metabolic response for energy
      metabolism during functional hypoxia, and the contribution of different metabolic
      pathways and various abalone tissues towards the overall accumulation of
      anaerobic end-products in abalone are scarce. Metabolomics analysis of adductor
      muscle, foot muscle, left gill, right gill, haemolymph and epipodial tissue
      samples indicated that South African abalone (Haliotis midae) subjected to
      functional hypoxia utilises predominantly anaerobic metabolism, and depends on
      all of the main metabolite classes (proteins, carbohydrates and lipids) for
      energy supply. Functional hypoxia caused increased levels of anaerobic end
      products: lactate, alanopine, tauropine, succinate and alanine. Also, elevation
      in arginine levels was detected, confirming that abalone use phosphoarginine to
      generate energy during functional hypoxia. Different tissues showed varied
      metabolic responses to hypoxia, with functional hypoxia showing excessive changes
      in the adductor muscle and gills. From this metabolomics investigation, it
      becomes evident that abalone are metabolically able to produce sufficient amounts
      of energy when functional hypoxia is experienced. Also, tissue interplay enables
      the adjustment of H. midae energy requirements as their metabolism shifts from
      aerobic to anaerobic respiration during functional hypoxia.This article has an
      associated First Person interview with the first author of the paper.

PMID- 29572262
TI  - Doctors can take blood from Skripals for chemical weapons testing, rules judge.

PMID- 29572260
TI  - Identification and characterization of host proteins bound to dengue virus 3' UTR
      reveal an antiviral role for quaking proteins.
AB  - The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses.
      These positive-strand viral genomes contain structured 3' untranslated regions
      (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs
      are functionally important in viral replication, pathogenesis, and defense
      against host immune mechanisms. Here, we combined RNA chromatography and
      quantitative mass spectrometry to identify proteins interacting with DENV1-4 3'
      UTRs. As expected, RBPs displayed distinct binding specificity. Among them, we
      focused on quaking (QKI) because of its preference for the DENV4 3' UTR (DENV
      4/SG/06K2270DK1/2005). RNA immunoprecipitation experiments demonstrated that QKI
      interacted with DENV4 genomes in infected cells. Moreover, QKI depletion enhanced
      infectious particle production of DENV4. On the contrary, QKI did not interact
      with DENV2 3' UTR, and DENV2 replication was not affected consistently by QKI
      depletion. Next, we mapped the QKI interaction site and identified a QKI response
      element (QRE) in DENV4 3' UTR. Interestingly, removal of QRE from DENV4 3' UTR
      abolished this interaction and increased DENV4 viral particle production.
      Introduction of the QRE to DENV2 3' UTR led to QKI binding and reduced DENV2
      infectious particle production. Finally, reporter assays suggest that QKI reduced
      translation efficiency of viral RNA. Our work describes a novel function of QKI
      in restricting viral replication.

PMID- 29572261
TI  - Clock-dependent chromatin topology modulates circadian transcription and
      behavior.
AB  - The circadian clock in animals orchestrates widespread oscillatory gene
      expression programs, which underlie 24-h rhythms in behavior and physiology.
      Several studies have shown the possible roles of transcription factors and
      chromatin marks in controlling cyclic gene expression. However, how daily active
      enhancers modulate rhythmic gene transcription in mammalian tissues is not known.
      Using circular chromosome conformation capture (4C) combined with sequencing (4C
      seq), we discovered oscillatory promoter-enhancer interactions along the 24-h
      cycle in the mouse liver and kidney. Rhythms in chromatin interactions were
      abolished in arrhythmic Bmal1 knockout mice. Deleting a contacted intronic
      enhancer element in the Cryptochrome 1 (Cry1) gene was sufficient to compromise
      the rhythmic chromatin contacts in tissues. Moreover, the deletion reduced the
      daily dynamics of Cry1 transcriptional burst frequency and, remarkably, shortened
      the circadian period of locomotor activity rhythms. Our results establish
      oscillating and clock-controlled promoter-enhancer looping as a regulatory layer
      underlying circadian transcription and behavior.

PMID- 29572263
TI  - Gender differences in the associations of body mass index, physical fitness and
      tobacco use with lower extremity musculoskeletal injuries among new US Army
      soldiers.
AB  - BACKGROUND: Musculoskeletal (MSK) injuries are a leading cause of morbidity among
      US Army soldiers, especially among women and the newly enlisted. While extremes
      of body mass index (BMI), low physical fitness and tobacco use have been
      identified as risk factors, no prior studies have determined the combined effects
      of these risk factors or tested for gender differences in the associations.
      METHODS: We conducted a retrospective cohort study utilising the Stanford
      Military Data Repository to study all enlisted soldier accessions to the US Army
      between January 2011 and January 2014, with follow-up through December 2014
      (n=238 772). We used discrete-time logistic regression to test for associations
      between demographic, socioeconomic and health behaviour-related predictors and
      incident lower extremity injuries. We included interaction terms to test for
      gender differences. RESULTS: Among men, there were greater adjusted odds of
      injury among underweight (OR 1.27), overweight (OR 1.14) and obese soldiers (OR
      1.54) (all p<0.001) relative to normal-weight soldiers. No statistically
      significant differences in the odds of injury on the basis of BMI were observed
      for female soldiers. Physical fitness was a significantly stronger predictor of
      injury for female as compared with male soldiers, while the association between
      tobacco use and injury was stronger for men (OR 1.47) than for women (OR 1.30)
      (p<0.001 for both). CONCLUSION: This is the largest known study to simultaneously
      assess important, modifiable musculoskeletal injury risk factors and to test for
      gender differences in these associations. These findings provide critical gender
      related nuances for clinicians and leaders seeking to reduce the risk of these
      problems.

PMID- 29572264
TI  - Co-targeting driver pathways in prostate cancer: two birds with one stone.

PMID- 29572266
TI  - Increase in fluoroscopic radiation dose in successive sessions of multistage Onyx
      embolization of brain arteriovenous malformations compared with the first
      session.
AB  - BACKGROUND AND PURPOSE: Onyx embolization is a treatment for brain arteriovenous
      malformations (AVMs). However, multistage embolization usually involves the
      presence of radiodense Onyx cast from the previous sessions, which may influence
      the fluoroscopic radiation dose. We compared the fluoroscopic dose between the
      initial and final embolization sessions. MATERIALS AND METHOD: From January 2014
      to September 2016, 18 patients underwent multistage Onyx embolization (more than
      twice) for brain AVMs. The total fluoroscopic duration (minutes), dose-area
      product (DAP, Gy*cm2), and cumulative air kerma (CAK, mGy) of both the frontal
      and lateral planes were obtained. We compared the frontal and lateral
      fluoroscopic dose rates (dose/time) of the final embolization session with those
      of the initial session. The relationship between the injected Onyx volume and
      radiation dose was tested. RESULTS: The initial and final procedures on the
      frontal plane showed significantly different fluoroscopic dose rates (DAP:
      initial 0.668 Gy*cm2/min, final 0.848 Gy*cm2/min, P=0.02; CAK: initial 12.7
      mGy/min, final 23.1 mGy/min, P=0.007). Those on the lateral plane also showed a
      similar pattern (DAP: initial 0.365 Gy*cm2/min, final 0.519 Gy*cm2/min, P=0.03;
      CAK: initial 6.2 mGy/min, final 12.9 mGy/min, P=0.01). The correlation between
      the cumulative Onyx volume (vials) and radiation dose ratio of both planes showed
      an increasing trend (rho 0.4325-0.7053; P=0.0011-0.0730). CONCLUSION: Owing to
      the automatic exposure control function during fluoroscopy, successive Onyx
      embolization procedures increase the fluoroscopic radiation dose in multistage
      brain AVM embolization because of the presence of radiodense Onyx mass.

PMID- 29572265
TI  - The Stereotactic Intracerebral Hemorrhage Underwater Blood Aspiration (SCUBA)
      technique for minimally invasive endoscopic intracerebral hemorrhage evacuation.
AB  - BACKGROUND: Endoscopic intracerebral hemorrhage (ICH) evacuation techniques have
      gained interest as a potential therapeutic option. However, the instrumentation
      and techniques employed are still being refined to optimize hemostasis and
      evacuation efficiency. OBJECTIVE: We describe the application of a specific
      endoscopic technique in the treatment of ICH called the Stereotactic
      Intracerebral Hemorrhage Underwater Blood Aspiration (SCUBA) technique. It
      differs from previously described minimally invasive ICH interventions in that it
      combines two separate neuroendoscopic strategies in two phases, the first under
      dry-field conditions and the second using a wet-field strategy. METHODS: All
      patients who underwent endoscopic ICH evacuation with the SCUBA technique from
      December 2015 to September 2017 were included. RESULTS: The SCUBA technique was
      performed in 47 patients. The average evacuation percentage was 88.2% (SD 20.8).
      Active bleeding identified to derive from a specific source was observed in 23
      (48.9%) cases. Active bleeding was addressed with irrigation alone in five cases
      (10.6%) and required electrocautery in 18 cases (38.3%). Intraoperative bleeding
      occurred in 3 patients (6.4%) and postoperative bleeding occurred in a single
      case (2.1%). CONCLUSIONS: The SCUBA technique provides surgeons with a defined
      strategy for true endoscopic hematoma evacuation. In particular, the fluid-filled
      cavity in SCUBA Phase 2 has the potential to provide several advantages over the
      traditional air-filled strategy, including clear identification and cauterization
      of bleeding vessels and visualization of residual clot burden. Further
      investigation is necessary to compare this technique to others that are currently
      used.

PMID- 29572267
TI  - Long-term visual outcome in patients treated by flow diversion for carotid
      ophthalmic aneurysms.
AB  - BACKGROUND: Flow-diverter stents (FDSs) are an upgrade in the treatment of
      intracranial aneurysms. However, complications concerning covered branches have
      been reported, especially the ophthalmic artery (OA). The purpose of our study
      was to evaluate the long-term ophthalmic complication rate of carotid-ophthalmic
      aneurysms (COA) without visual pathways compression, treated by a FDS covering
      the OA by performing an exhaustive ophthalmic examination. MATERIAL AND METHODS:
      Retrospective analysis of a single-center database screening the patients treated
      from October 2009 to April 2015 for an intracranial aneurysm with a FDS. The
      patients treated for a non-compressive COA with coverage of the OA by the device
      were studied (n=30). Among these patients, 15 (50%) were excluded. The remaining
      15 patients underwent a systematic and extensive ophthalmic examination at least
      2 years after the stent placement by two ophthalmologists. RESULTS: Fifteen
      patients with 16 COAs treated with a FDS were included. Mean follow-up was 4.1+/
      2 years. Six patients (40%), presented ophthalmic complications, including three
      fugax amauroses (18.8%) and four significant visual field defects (25%). After
      comparing each eye's visual field's patients, we observed a significant
      difference between the eye on the FDS side compared with the contralateral eye,
      with a mean deviation of -1.58 dB versus -0.67 dB respectively (P=0.003). Visual
      acuity was preserved in all patients. CONCLUSION: Patients treated by FDS for COA
      have a good long-term clinical ophthalmic outcome. However, extensive ophthalmic
      examination shows a high percentage of minor ophthalmic modifications.
      Interventional neuroradiologists should be aware of these possible complications
      when choosing to treat these aneurysms with FDS.

PMID- 29572268
TI  - A transcription factor network represses CFTR gene expression in airway
      epithelial cells.
AB  - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
      cause the inherited disorder cystic fibrosis (CF). Lung disease is the major
      cause of CF morbidity, though CFTR expression levels are substantially lower in
      the airway epithelium than in pancreatic duct and intestinal epithelia, which
      also show compromised function in CF. Recently developed small molecule
      therapeutics for CF are highly successful for one specific CFTR mutation and have
      a positive impact on others. However, the low abundance of CFTR transcripts in
      the airway limits the opportunity for drugs to correct the defective substrate.
      Elucidation of the transcriptional mechanisms for the CFTR locus has largely
      focused on intragenic and intergenic tissue-specific enhancers and their
      activating trans-factors. Here, we investigate whether the low CFTR levels in the
      airway epithelium result from the recruitment of repressive proteins directly to
      the locus. Using an siRNA screen to deplete ~1500 transcription factors (TFs) and
      associated regulatory proteins in Calu-3 lung epithelial cells, we identified
      nearly 40 factors that upon depletion elevated CFTR mRNA levels more than 2-fold.
      A subset of these TFs was validated in primary human bronchial epithelial cells.
      Among the strongest repressors of airway expression of CFTR were Kruppel-like
      factor 5 and Ets homologous factor, both of which have pivotal roles in the
      airway epithelium. Depletion of these factors, which are both recruited to an
      airway-selective cis-regulatory element at -35 kb from the CFTR promoter,
      improved CFTR production and function, thus defining novel therapeutic targets
      for enhancement of CFTR.

PMID- 29572269
TI  - Massive haemoptysis TB or not TB.

PMID- 29572270
TI  - Cardiopulmonary rehabilitation for obese sleep-disordered breathing: a new
      treatment frontier?

PMID- 29572271
TI  - Effect and impact of mechanical ventilation in myotonic dystrophy type 1: a
      prospective cohort study.
AB  - Few studies have assessed the impact of home ventilation in patients with
      myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We
      assessed the survival associated with category of home ventilation adherence of
      patients with DM1 followed up at a home ventilation unit using a Cox proportional
      hazards model. 218 patients were included; those who refused or delayed their
      acceptance of non-invasive ventilation were at higher risk for severe events
      (invasive ventilation or death) (P=0.03). Risk of death was associated with
      orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to
      90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home
      ventilation as prescribed may be associated with increased mortality in patients
      with DM1.

PMID- 29572272
TI  - Uric acid, lung function and COPD: a causal link is unlikely.

PMID- 29572274
TI  - No place to run: Plants have evolved a dazzling array of chemical defences and
      regulatory networks that matches the mammalian immune system for complexity.

PMID- 29572273
TI  - Heterochromatin and cohesion protection at human centromeres: the final say of a
      long controversy?

PMID- 29572275
TI  - Heartbeat: Acute myocardial infarction: one test to diagnose them all?

PMID- 29572276
TI  - Reaching the wrong conclusion: residual confounding by indication.

PMID- 29572277
TI  - White matter abnormalities and cognition in patients with conflicting diagnoses
      and CSF profiles.
AB  - OBJECTIVE: To determine whether white matter changes influence progression of
      cognitive decline in individuals with clinically diagnosed Alzheimer disease (AD)
      and differing biomarker profiles. METHODS: Two hundred thirty-six individuals
      from the Alzheimer's Disease Neuroimaging Initiative database with clinical
      diagnoses of cognitively normal older adult (older controls [OCs]), mild
      cognitive impairment, and AD were studied. Support vector machine experiments
      were first performed to determine the utility of various biomarkers for
      classifying individuals by clinical diagnosis. General linear models were
      implemented to assess the relationships between CSF measures of beta-amyloid 1
      42, phosphorylated tau181p, and MRI-based white matter signal abnormality (WMSA)
      volumes and cognitive decline. Analyses were performed across all patients as
      well as within subgroups of individuals that were defined by clinical cutoff
      points for both CSF measures. RESULTS: CSF biomarkers alone classified
      individuals with AD vs OCs with 82% accuracy, and the addition of WMSA did not
      enhance this. Both CSF biomarkers as well as WMSA volume significantly
      contributed to predicting cognitive decline in executive and memory domains when
      assessed across all 236 individuals. In individuals with pathologic levels of
      both CSF biomarkers, WMSA only significantly contributed to models of future
      executive function decline. In individuals with subpathologic CSF biomarker
      levels (levels similar to those in OC individuals), WMSA significantly
      contributed to prediction of memory decline and were the sole significant
      predictor of executive function decline. CONCLUSIONS: WMSA hold additional
      predictive power regarding cognitive progression in older individuals and are
      most effective as biomarkers in individuals who are cognitively impaired but do
      not fit the expected CSF biomarker profile of AD.

PMID- 29572278
TI  - IV steroids during long episodes of Kleine-Levin syndrome.
AB  - OBJECTIVE: To retrospectively compare the benefits (episode cessation) and risks
      of IV methylprednisolone (IV-MP) vs abstention during prolonged Kleine-Levin
      syndrome (KLS) episodes. METHODS: A total of 26 patients with KLS received 1 g/d
      IV-MP for 3 days during 1 to 6 episodes each (totaling 43 IV-MP sessions). The
      change of episode duration with IV-MP (vs previous episode duration) was compared
      with the change duration between 2 consecutive episodes in 48 untreated patients
      matched for age, sex, age at KLS onset, number of episodes, and disease duration
      (more treated than untreated patients had long episodes). RESULTS: Eleven
      patients (42.3%) had an episode that was at least 1 week shorter than the
      preceding one when they received IV-MP therapy, whereas shorter episodes were
      significantly less frequent (10.4%) in the untreated group. This benefit was more
      marked (65.5% responders, 12 fewer days in an episode vs 0 days in the untreated
      patients) when IV-MP was infused before the 10th day of the episode. Mild,
      transient adverse effects (insomnia, muscle pain, nervousness/restlessness, but
      no manic switching) were reported by 61.3% of patients. No specific responder
      profile was identified. CONCLUSION: In this open-labeled, naturalistic study,
      early IV-MP (following the protocol for multiple sclerosis relapses) had a good
      benefit/risk ratio during KLS episodes in patients with long episodes (with half
      of the patients having an early cessation of episodes). CLASSIFICATION OF
      EVIDENCE: This study provides Class IV evidence that for patients with long
      episodes of KLS, IV steroids decrease the duration of KLS episodes.

PMID- 29572279
TI  - Amyloid "accumulators": The next generation of candidates for amyloid-targeted
      clinical trials?

PMID- 29572280
TI  - Beta oscillations and urinary voiding in Parkinson disease.
AB  - OBJECTIVES: To investigate the role of beta oscillations in urinary voiding and
      their association with lower urinary tract symptoms in Parkinson disease (PD).
      METHODS: We used surgically implanted deep brain stimulation electrodes to record
      local field potential signals from the subthalamic nucleus (STN) and globus
      pallidus interna (GPi) of patients with PD during urinary voiding. Five patients
      with STN electrodes and 5 patients with GPi electrodes were tested. We also
      explored correlations between beta oscillatory power and urinary symptoms
      assessed by the International Consultation on Incontinence Lower Urinary Tract
      Symptoms questionnaire. RESULTS: Beta suppression occurred during urinary voiding
      in the GPi (p < 0.05) but not the STN. Furthermore, the beta signal in the GPi
      during voiding correlated significantly with severity of incontinence and urinary
      frequency (p < 0.05). CONCLUSIONS: In this study, we have demonstrated that local
      field potentials can provide information about the neural control of the bladder.
      Our findings suggest that the GPi is implicated in the process of urinary voiding
      and that its mechanism of action is linked to signals in the beta frequency band.
      Moreover, our correlational analyses show that beta oscillations may be
      implicated more generally in the pathophysiology of lower urinary tract symptoms
      in PD.

PMID- 29572281
TI  - Biomarker-based analysis of preclinical progression in spinal and bulbar muscular
      atrophy.
AB  - OBJECTIVE: To identify a candidate biomarker reflecting biological changes during
      the preclinical progression of spinal and bulbar muscular atrophy (SBMA).
      METHODS: We analyzed longitudinal changes in biochemical parameters obtained
      during health examinations before and after the diagnosis of SBMA. We estimated
      trajectories of clinical markers across years from the onset of weakness using
      linear mixed models and compared these trajectories with those estimated for male
      healthy controls and patients with amyotrophic lateral sclerosis (ALS) and
      Parkinson disease (PD). Moreover, we examined the relationship between serum
      creatinine level and the onset of symptoms using Kaplan-Meier curves. RESULTS:
      Between October 2014 and October 2017, we enrolled 40 patients with genetically
      confirmed SBMA, 48 healthy controls, 25 patients with ALS, and 20 patients with
      PD. In patients with SBMA, we evaluated the patients' data for a period of 17.3
      +/- 7.5 years, including 11.4 +/- 7.1 years of preclinical phase. Decreases in
      serum creatinine occurred >10 years before the onset. The mean serum creatinine
      concentration was 0.56 mg/dL at the onset of weakness in patients with SBMA
      compared to 0.88 +/- 0.10 mg/dL on final evaluation in healthy controls. Serum
      levels of alanine transaminase and aspartate transaminase showed tendencies to
      increase in preclinical SBMA. These preclinical changes of biomarkers were not
      observed in either ALS or PD. CONCLUSIONS: Our findings suggest that serum
      creatinine begins to decrease before the onset of clinical symptoms and is a
      biomarker for disease progression and the efficacy of therapeutics in preclinical
      SBMA.

PMID- 29572282
TI  - Memory decline accompanies subthreshold amyloid accumulation.
AB  - OBJECTIVE: Extensive cortical beta-amyloid (Abeta positivity) has been linked to
      cognitive decline, but the clinical significance of elevations in Abeta within
      the negative range is unknown. METHODS: We examined amyloid and cognitive
      trajectories (memory, executive function) in 142 cognitively normal older
      individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative who were
      Abeta-negative at baseline and who had at least 2 [18F]-florbetapir PET scans
      over 3.9 +/- 1.4 years. We determined whether Abeta accumulation was associated
      with longitudinal changes in memory or executive function. RESULTS: Among
      baseline-negative individuals, florbetapir slope (mean annual increase 0.002 +/-
      0.008 standardized uptake value ratio units/y) was not related to age, sex,
      education, APOE4 status, baseline memory or executive function, temporoparietal
      glucose metabolism, baseline hippocampal volume, or hippocampal volume change;
      but it was related to higher baseline cortical florbetapir, indicating that Abeta
      accumulation was ongoing at baseline in those who accumulated during the study.
      Over the course of follow-up, 13 individuals converted to florbetapir+ and 14
      nearly nonoverlapping individuals converted to mild cognitive impairment or
      Alzheimer disease. Amyloid accumulation among baseline-negative individuals was
      associated with poorer longitudinal memory performance (p = 0.019), but it was
      not associated with changes in executive function. Reducing the sample to
      individuals with at least 3 timepoints to estimate the florbetapir slope
      strengthened the relationship further between florbetapir accumulation and memory
      decline (p = 0.007). CONCLUSIONS: Memory decline accompanies Abeta accumulation
      in otherwise healthy, Abeta-negative older adults. Amyloid increases within the
      negative range may represent the earliest detectable indication of pathology with
      domain-specific cognitive consequences.

PMID- 29572283
TI  - Cerebellar volume as an imaging marker of development in infants with tuberous
      sclerosis complex.
AB  - OBJECTIVE: In this cohort analysis, we studied 1-year-old infants with tuberous
      sclerosis complex (TSC), correlating volumes of cerebellar structures with
      neurodevelopmental measures. METHODS: We analyzed data from a prospective
      biomarker study in infants with TSC (ClinicalTrials.gov NCT01780441). We included
      participants aged 12 months with an identified mutation of TSC1 or TSC2. Using
      MRI segmentation performed with the PSTAPLE algorithm, we measured relative
      volumes (structure volume divided by intracranial contents volume) of the
      following structures: right/left cerebellar white matter, right/left cerebellar
      exterior, vermal lobules I-V, vermal lobules VI-VII, and vermal lobules VIII-X.
      We correlated relative volumes to Mullen Scales of Early Learning (MSEL) scores.
      RESULTS: There were 70 participants (mean age 1.03 [0.11] years): n = 11 had a
      TSC1 mutation; n = 59 had a TSC2 mutation. For patients with TSC2 mutation, for
      every percentage increase in total cerebellar volume, there was an approximate 10
      point increase in MSEL composite score (beta = 10.47 [95% confidence interval
      5.67, 15.27], p < 0.001). For patients with TSC1 mutation, the relationship
      between cerebellar volume and MSEL composite score was not statistically
      significant (beta = -10.88 [95% confidence interval -22.16, 0.41], p = 0.06). For
      patients with TSC2 mutation, there were positive slopes when regressing
      expressive language and visual reception skills with volumes of nearly all
      cerebellar structures (p <= 0.29); there were also positive slopes when
      regressing receptive language skills, gross motor skills, and fine motor skills
      with volumes of cerebellar right/left exterior (p <= 0.014). CONCLUSIONS:
      Cerebellar volume loss-perhaps reflecting Purkinje cell degeneration-may predict
      neurodevelopmental severity in patients with TSC2 mutations.

PMID- 29572284
TI  - Aminophylline for treatment of postdural puncture headache: A randomized clinical
      trial.
AB  - OBJECTIVE: To investigate the efficacy and safety of IV aminophylline for
      patients with postdural puncture headache (PDPH). METHODS: We randomly assigned
      patients to groups receiving either 250 mg IV aminophylline or a placebo within 3
      hours of symptom onset once daily for 2 consecutive days. The primary endpoint
      was headache severity 8 hours after treatment. We assessed this using visual
      analog scale (VAS) scores taken from patients in a standing position. We also
      recorded posttreatment VAS score changes, Patient Global Impression of Change
      (PGIC) scores, and adverse events. We performed an intention-to-treat analysis.
      RESULTS: We enrolled 126 patients with PDPH at 5 centers in China (62 assigned to
      the aminophylline group and 64 to the placebo group). The median age was 37
      years, and 96 (76.2%) patients were women. Compared to the placebo-treated
      patients, the aminophylline-treated patients had significantly lower mean VAS
      scores 8 hours after treatment (5.34 vs 2.98, p < 0.001) and were significantly
      more likely to report improvements on the PGIC (39.1% vs 72.6%, p < 0.01). This
      therapeutic effect was already evident at the 30-minute time point and persisted
      for 2 days. There was no significant difference in the incidence of adverse
      events (4.8% vs 1.6%, p = 0.589). CONCLUSIONS: IV aminophylline is an effective
      and safe early-stage treatment for patients with PDPH. CLINICALTRIALSGOV
      IDENTIFIER: NCT02522013. CLASSIFICATION OF EVIDENCE: This study provides Class I
      evidence that for people with PDPH, IV aminophylline reduces headache severity.

PMID- 29572285
TI  - Palatal tremor as a presenting symptom of amyotrophic lateral sclerosis.

PMID- 29572287
TI  - Allergen-Specific Immunotherapy in the Treatment of Pediatric Asthma: A
      Systematic Review.
AB  - CONTEXT: Treatment options for allergic asthma include allergen avoidance,
      pharmacotherapy, and allergen immunotherapy. OBJECTIVES: Summarize and update
      current evidence for the efficacy and safety of subcutaneous immunotherapy (SCIT)
      and sublingual immunotherapy (SLIT) in pediatric allergic asthma. DATA SOURCES:
      PubMed, Embase, Cochrane Central Register of Controlled Trials (January 1, 2005,
      through May 8, 2017), ClinicalTrials.gov, and the US Food and Drug Administration
      Adverse Event Reporting System. We reevaluated trials from our 2013 systematic
      review. STUDY SELECTION: We included studies with children <=18 years of age in
      which researchers reported on prespecified outcomes and had an intervention arm
      receiving aeroallergen SCIT or SLIT. Only randomized controlled trials (RCTs)
      were included for efficacy. RCTs and non-RCTs were included for safety outcomes.
      DATA EXTRACTION: Two reviewers extracted data. We included 40 studies (17 SCIT
      trials, 11 SLIT trials, 8 non-RCTs for SCIT safety, and 4 non-RCTs for SLIT
      safety). RESULTS: We found moderate-strength evidence that SCIT reduces long-term
      asthma medication use. We found low-strength evidence that SCIT improves asthma
      related quality of life and forced expiratory volume in 1 second. There was also
      low-strength evidence that SLIT improves medication use and forced expiratory
      volume in 1 second. There was insufficient evidence on asthma symptoms and health
      care use. LIMITATIONS: There were no trials in which researchers evaluated asthma
      symptoms using a validated tool. Study characteristics and outcomes were reported
      heterogeneously. CONCLUSIONS: In children with allergic asthma, SCIT may reduce
      long-term asthma medication use. Local and systemic allergic reactions are
      common, but anaphylaxis is reported rarely.

PMID- 29572286
TI  - Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in
      Diabetes: A Comparative Effectiveness Study.
AB  - BACKGROUND AND OBJECTIVES: In individuals with diabetes, the comparative
      effectiveness of add-on antihypertensive medications added to an angiotensin
      converting enzyme inhibitor or angiotensin II receptor blocker on the risk of
      significant kidney events is unknown. DESIGN, SETTING PARTICIPANTS, &
      MEASUREMENTS: We used an observational, multicenter cohort of 21,897 individuals
      with diabetes to compare individuals who added beta-blockers, dihydropyridine
      calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin
      converting enzyme inhibitors or angiotensin II receptor blockers. We examined the
      hazard of significant kidney events, cardiovascular events, and death using Cox
      proportional hazard models with propensity score weighting. The composite
      significant kidney event end point was defined as the first occurrence of a >=30%
      decline in eGFR to an eGFR<60 ml/min per 1.73 m2, initiation of dialysis, or
      kidney transplant. The composite cardiovascular event end point was defined as
      the first occurrence of hospitalization for acute myocardial infarction, acute
      coronary syndrome, stroke, or congestive heart failure; coronary artery bypass
      grafting; or percutaneous coronary intervention, and it was only examined in
      those free of cardiovascular disease at baseline. RESULTS: Over a maximum of 5
      years, there were 4707 significant kidney events, 1498 deaths, and 818
      cardiovascular events. Compared with thiazide diuretics, hazard ratios for
      significant kidney events for beta-blockers, calcium channel blockers, and loop
      diuretics were 0.81 (95% confidence interval, 0.74 to 0.89), 0.67 (95% confidence
      interval, 0.58 to 0.78), and 1.19 (95% confidence interval, 1.00 to 1.41),
      respectively. Compared with thiazide diuretics, hazard ratios of mortality for
      beta-blockers, calcium channel blockers, and loop diuretics were 1.19 (95%
      confidence interval, 0.97 to 1.44), 0.73 (95% confidence interval, 0.52 to 1.03),
      and 1.67 (95% confidence interval, 1.31 to 2.13), respectively. Compared with
      thiazide diuretics, hazard ratios of cardiovascular events for beta-blockers,
      calcium channel blockers, and loop diuretics compared with thiazide diuretics
      were 1.65 (95% confidence interval, 1.39 to 1.96), 1.05 (95% confidence interval,
      0.80 to 1.39), and 1.55 (95% confidence interval, 1.05 to 2.27), respectively.
      CONCLUSIONS: Compared with thiazide diuretics, calcium channel blockers were
      associated with a lower risk of significant kidney events and a similar risk of
      cardiovascular events.

PMID- 29572288
TI  - Incidence and Costs of Neonatal Abstinence Syndrome Among Infants With Medicaid:
      2004-2014.
AB  - OBJECTIVES: To describe incidence, health care use, and cost trends for infants
      with neonatal abstinence syndrome (NAS) who are covered by Medicaid compared with
      other infants. METHODS: We used 2004-2014 hospital birth data from the National
      Inpatient Sample, a nationally representative sample of hospital discharges in
      the United States (N = 13 102 793). Characteristics and trends among births
      impacted by NAS were examined by using univariate statistics and logistic
      regression. RESULTS: Medicaid covered 73.7% of NAS-related births in 2004 (95%
      confidence interval [CI], 68.9%-77.9%) and 82.0% of NAS-related births in 2014
      (95% CI, 80.5%-83.5%). Among infants covered by Medicaid, NAS incidence increased
      more than fivefold during our study period, from 2.8 per 1000 births (95% CI, 2.1
      3.6) in 2004 to 14.4 per 1000 births (95% CI, 12.9-15.8) in 2014. Infants with
      NAS who were covered by Medicaid were significantly more likely to be transferred
      to another hospital and have a longer length of stay than infants without NAS who
      were enrolled in Medicaid or infants with NAS who were covered by private
      insurance. Adjusting for inflation, total hospital costs for NAS births that were
      covered by Medicaid increased from $65.4 million in 2004 to $462 million in 2014.
      The proportion of neonatal hospital costs due to NAS increased from 1.6% in 2004
      to 6.7% in 2014 among births that were covered by Medicaid. CONCLUSIONS: The
      number of Medicaid-financed births that are impacted by NAS has risen
      substantially and totaled $462 million in hospital costs in 2014. Improving
      affordable health insurance coverage for low-income women before pregnancy would
      expand access to substance use disorder treatment and could reduce NAS-related
      morbidity and costs.

PMID- 29572289
TI  - Reduced salivary secretion contributes more to changes in the oral microbiome of
      patients with primary Sjogren's syndrome than underlying disease.

PMID- 29572290
TI  - Comment on: 'Evaluation of the impact of concomitant fibromyalgia on TNF alpha
      blockers' effectiveness in axial spondyloarthritis: results of a prospective,
      multicentre study' by Molto et al: still a long way to go in the assessment of
      patients with spondyloarthritis and concomitant fibromyalgia?

PMID- 29572292
TI  - Checkpoint inhibitors and arthritis.

PMID- 29572291
TI  - Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of
      seasonal influenza vaccination in patients with rheumatoid arthritis: a
      randomised clinical trial.
AB  - OBJECTIVE: To determine whether a 2-week methotrexate (MTX) discontinuation after
      vaccination improves the efficacy of seasonal influenza vaccination in patients
      with rheumatoid arthritis (RA). METHODS: In this prospective randomised parallel
      group multicentre study, patients with RA on stable dose of MTX were randomly
      assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016
      2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata
      and B-Victoria. The primary outcome was frequency of satisfactory vaccine
      response, defined as greater than or equal to fourfold increase of
      haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination
      against >=2 of four vaccine strains. Secondary endpoints included seroprotection
      (ie, HI titre >=1:40) rate, fold change in antibody titres. RESULTS: The modified
      intention-to-treat population included 156 patients in the MTX-continue group and
      160 patients in the MTX-hold group. More patients in MTX-hold group achieved
      satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%,
      p<0.001). Seroprotection rate was higher in the MTX-hold group than the MTX
      continue group for all four antigens (H1N1: difference 10.7%, 95% CI 2.0% to
      19.3%; H3N2: difference 15.9%, 95% CI 5.9% to 26.0%; B-Yamagata: difference13.7%,
      95% CI 5.2% to 22.4%; B-Victoria: difference 14.7%, 95% CI 4.5% to 25.0%). The
      MTX-hold group showed higher fold increase in their antibody titres against all
      four influenza antigens (all p<0.05). Change in disease activity was similar
      between groups. CONCLUSIONS: A temporary MTX discontinuation for 2 weeks after
      vaccination improves the immunogenicity of seasonal influenza vaccination in
      patients with RA without increasing RA disease activity. TRIAL REGISTRATION:
      NCT02897011.

PMID- 29572293
TI  - Prominent inter-scallop separations of the posterior leaflet of the mitral valve:
      an important cause of 'pathological' mitral regurgitation.
AB  - The 2012 World Heart Federation (WHF) criteria for echocardiographic diagnosis of
      rheumatic heart disease (RHD) identify that the finding of 'pathological' mitral
      regurgitation (MR) in a screened individual increases the likelihood of detecting
      underlying RHD. Cases of isolated "pathological MR are thus identified as
      'borderline RHD'. A large-scale echocardiographic screening program (Echo in
      Africa) in South Africa has identified that inter-scallop separations of the
      posterior mitral valve leaflet (PMVL) can give rise to 'pathological' MR. The
      authors propose that this finding when associated with isolated 'pathological' MR
      is unrelated to the rheumatic disease process. In this case report, we present
      two examples of 'pathological' MR related to inter-scallop separation from the
      Echo in Africa image database. We provide additional screening tips to accurately
      identify this entity.

PMID- 29572296
TI  - Correction to "Amlexanox Inhibits Cerebral Ischemia-Induced Delayed Astrocytic
      High-Mobility Group Box 1 Release and Subsequent Brain Damage".

PMID- 29572295
TI  - Socioeconomic adversity-an important barrier to healthy aging.

PMID- 29572294
TI  - Systematic characterization of pan-cancer mutation clusters.
AB  - Cancer genome sequencing has shown that driver genes can often be distinguished
      not only by the elevated mutation frequency but also by specific nucleotide
      positions that accumulate changes at a high rate. However, properties associated
      with a residue's potential to drive tumorigenesis when mutated have not yet been
      systematically investigated. Here, using a novel methodological approach, we
      identify and characterize a compendium of 180 hotspot residues within 160 human
      proteins which occur with a significant frequency and are likely to have
      functionally relevant impact. We find that such mutations (i) are more prominent
      in proteins that can exist in the on and off state, (ii) reflect the identity of
      a tumor of origin, and (iii) often localize within interfaces which mediate
      interactions with other proteins or ligands. Following, we further examine
      structural data for human protein complexes and identify a number of additional
      protein interfaces that accumulate cancer mutations at a high rate. Jointly,
      these analyses suggest that disruption and dysregulation of protein interactions
      can be instrumental in switching functions of cancer proteins and activating
      downstream changes.

PMID- 29572297
TI  - Overdiagnosis and overtreatment as a quality problem: insights from healthcare
      improvement research.

PMID- 29572298
TI  - Impact of a commercial order entry system on prescribing errors amenable to
      computerised decision support in the hospital setting: a prospective pre-post
      study.
AB  - BACKGROUND: In this UK study, we investigated the impact of computerised
      physician order entry (CPOE) and clinical decision support (CDS) implementation
      on the rate of 78 high-risk prescribing errors amenable to CDS. METHODS: We
      conducted a preintervention/postintervention study in three acute hospitals in
      England. A predefined list of prescribing errors was incorporated into an audit
      tool. At each site, approximately 4000 prescriptions were reviewed both pre-CPOE
      and 6 months post-CPOE implementation. The number of opportunities for error and
      the number of errors that occurred were collated. Error rates were then
      calculated and compared between periods, as well as by the level of CDS. RESULTS:
      The prescriptions of 1244 patients were audited pre-CPOE and 1178 post-CPOE
      implementation. A total of 28 526 prescriptions were reviewed, with 21 138
      opportunities for error identified based on 78 defined errors. Across the three
      sites, for those prescriptions where opportunities for error were identified, the
      error rate was found to reduce significantly post-CPOE implementation, from 5.0%
      to 4.0% (P<0.001). CDS implementation by error type was found to differ
      significantly between sites, ranging from 0% to 88% across clinical
      contraindication, dose/frequency, drug interactions and other error types
      (P<0.001). Overall, 43/78 (55%) of the errors had some degree of CDS implemented
      in at least one of the hospitals. CONCLUSIONS: Implementation of CPOE with CDS
      was associated with clinically important reductions in the rate of high-risk
      prescribing errors. Given the pre-post design, these findings however need to be
      interpreted with caution. The occurrence of errors was found to be highly
      dependent on the level of restriction of CDS presented to the prescriber, with
      the effect that different configurations of the same CPOE system can produce very
      different results.

PMID- 29572299
TI  - Perceptions of rounding checklists in the intensive care unit: a qualitative
      study.
AB  - BACKGROUND: Rounding checklists are an increasingly common quality improvement
      tool in the intensive care unit (ICU). However, effectiveness studies have shown
      conflicting results. We sought to understand ICU providers' perceptions of
      checklists, as well as barriers and facilitators to effective utilisation of
      checklists during daily rounds. OBJECTIVES: To understand how ICU providers
      perceive rounding checklists and develop a framework for more effective rounding
      checklist implementation. METHODS: We performed a qualitative study in 32 ICUs
      within 14 hospitals in a large integrated health system in the USA. We used two
      complementary data collection methods: direct observation of daily rounds and
      semistructured interviews with ICU clinicians. Observations and interviews were
      thematically coded and primary themes were identified using a combined inductive
      and deductive approach. RESULTS: We conducted 89 interviews and performed 114
      hours of observation. Among study ICUs, 12 used checklists and 20 did not.
      Participants described the purpose of rounding checklists as a daily reminder for
      evidence-based practices, a tool for increasing shared understanding of patient
      care across care providers and a way to increase the efficiency of rounds.
      Checklists were perceived as not helpful when viewed as overstandardising care
      and when they are not relevant to a particular ICU's needs. Strategies to improve
      checklist implementation include attention to the brevity and relevance of the
      checklist to the particular ICU, consistent use over time, and integration with
      daily work flow. CONCLUSION: Our results provide potential insights about why ICU
      rounding checklists frequently fail to improve outcomes and offer a framework for
      effective checklist implementation through greater feedback and accountability.

PMID- 29572301
TI  - Reports offer window on medical aid in dying.

PMID- 29572302
TI  - Pharmacists contribute to integrated health systems' approaches to opioid safety.

PMID- 29572300
TI  - Speak up-related climate and its association with healthcare workers' speaking up
      and withholding voice behaviours: a cross-sectional survey in Switzerland.
AB  - OBJECTIVES: To determine frequencies of healthcare workers (HCWs) speak up
      related behaviours and the association of speak up-related safety climate with
      speaking up and withholding voice. DESIGN: Cross-sectional survey of doctors and
      nurses. Data were analysed using multilevel logistic regression models SETTING: 4
      hospitals with a total of nine sites from the German, French and Italian speaking
      part of Switzerland. PARTICIPANTS: Survey data were collected from 979 nurses and
      doctors. MAIN OUTCOME MEASURES: Frequencies of perceived patient safety concerns,
      of withholding voice and of speaking up behaviour. Speak up-related climate
      measures included psychological safety, encouraging environment and resignation.
      RESULTS: Perceived patient safety concerns were frequent among doctors and nurses
      (between 62% and 80% reported at least one safety concern during the last 4 weeks
      depending on the single items). Withholding voice was reported by 19%-39% of
      HCWs. Speaking up was reported by more than half of HCWs (55%-76%). The frequency
      of perceived concerns during the last 4 weeks was positively associated with both
      speaking up (OR=2.7, p<0.001) and withholding voice (OR=1.6, p<0.001). An
      encouraging environment was related to higher speaking up frequency (OR=1.3,
      p=0.005) and lower withholding voice frequency (OR=0.82, p=0.006). Resignation
      was associated with withholding voice (OR=1.5, p<0.001). The variance in both
      voicing behaviours attributable to the hospital-site level was marginal.
      CONCLUSIONS: Our results strengthen the importance of a speak up-supportive
      safety climate for staff safety-related communication behaviours, specifically
      withholding voice. This study indicates that a poor climate, in particular high
      levels of resignation among HCWs, is linked to frequent 'silence' of HCWs but not
      inversely associated with frequent speaking up. Interventions addressing safety
      related voicing behaviours should discriminate between withholding voice and
      speaking up.

PMID- 29572303
TI  - Federal data indicate positive labor market for hospital pharmacists.

PMID- 29572305
TI  - Multihospital health systems: Growing complexity of pharmacy enterprise brings
      opportunities and challenges.

PMID- 29572306
TI  - Safety concerns regarding selexipag in pulmonary arterial hypertension.

PMID- 29572307
TI  - Safety concerns regarding selexipag in pulmonary arterial hypertension.

PMID- 29572308
TI  - Association between hyperinsulinemia-euglycemia therapy and hyponatremia.

PMID- 29572309
TI  - Association between hyperinsulinemia-euglycemia therapy and hyponatremia.

PMID- 29572310
TI  - Multihospital health systems: Seize the opportunity.

PMID- 29572311
TI  - Utilizing big data to provide better health at lower cost.
AB  - PURPOSE: The efficient use of big data in order to provide better health at a
      lower cost is described. SUMMARY: As data become more usable and accessible in
      healthcare, organizations need to be prepared to use this information to
      positively impact patient care. In order to be successful, organizations need
      teams with expertise in informatics and data management that can build new
      infrastructure and restructure existing infrastructure to support quality and
      process improvements in real time, such as creating discrete data fields that can
      be easily retrieved and used to analyze and monitor care delivery. Organizations
      should use data to monitor performance (e.g., process metrics) as well as the
      health of their populations (e.g., clinical parameters and health outcomes). Data
      can be used to prevent hospitalizations, combat opioid abuse and misuse, improve
      antimicrobial stewardship, and reduce pharmaceutical spending. These examples
      also serve to highlight lessons learned to better use data to improve health. For
      example, data can inform and create efficiencies in care and engage and
      communicate with stakeholders early and often, and collaboration is necessary to
      have complete data. To truly transform care so that it is delivered in a way that
      is sustainable, responsible, and patient-centered, health systems need to act on
      these opportunities, invest in big data, and routinely use big data in the
      delivery of care. CONCLUSION: Using data efficiently has the potential to improve
      the care of our patients and lower cost. Despite early successes, barriers to
      implementation remain including data acquisition, integration, and usability.

PMID- 29572312
TI  - Creating organizational value by leveraging the multihospital pharmacy
      enterprise.
AB  - PURPOSE: The results of a survey of multihospital pharmacy leaders are
      summarized, and a road map for creating organizational value with the pharmacy
      enterprise is presented. SUMMARY: A survey was designed to evaluate the level of
      integration of pharmacy services across each system's multiple hospitals,
      determine the most commonly integrated services, determine whether value was
      quantified when services were integrated, collect common barriers for finding
      value through integration, and identify strategies for successfully overcoming
      these barriers. The comprehensive, 59-question survey was distributed
      electronically in September 2016 to the top pharmacy executive at approximately
      160 multihospital systems located throughout the United States. Survey
      respondents indicated that health systems are taking a wide range of approaches
      to integrating services systemwide. Several themes emerged from the survey
      responses: (1) having a system-level pharmacy leader with solid-line reporting
      across the enterprise increased the likelihood of integrating pharmacy services
      effectively, (2) integration of pharmacy services across a multihospital system
      was unlikely to decrease the number of pharmacy full-time equivalents within the
      enterprise, and (3) significant opportunities exist for creating value for the
      multihospital health system with the pharmacy enterprise, particularly within 4
      core areas: system-level drug formulary and clinical standardization initiatives,
      supply chain initiatives, electronic health record integration, and specialty and
      retail pharmacy services. CONCLUSION: Consistently demonstrating strong
      organizational leadership, entrepreneurialism, and the ability to create value
      for the organization will lead to the system-level pharmacy leader and the
      pharmacy enterprise being well-positioned to achieve positive outcomes for
      patients, payers, and the broader health system.

PMID- 29572313
TI  - Strategies for success in creating an effective multihospital health-system
      pharmacy and therapeutics committee.
AB  - PURPOSE: Lessons learned from the creation of a multihospital health-system
      formulary management and pharmacy and therapeutics (P&T) committee are described.
      SUMMARY: A health system can create and implement a multihospital system
      formulary and P&T committee to provide evidence-based medications for ideal
      healthcare. The formulary and P&T process should be multidisciplinary and include
      adequate representation from system hospitals. The aim of a system formulary and
      P&T committee is standardization; however, the system should allow flexibility
      for differences. Key points for a successful multihospital system formulary and
      P&T committee are patience, collaboration, resilience, and communication. When
      establishing a multihospital health-system formulary and P&T committee, the needs
      of individual hospitals are crucial. A designated member of the pharmacy
      department needs to centrally coordinate and manage formulary requests,
      medication reviews and monographs, meeting agendas and minutes, and a summary of
      decisions for implementation. It is imperative to create a timeline for formulary
      reviews to set expectations, as well as a process for formulary appeals.
      Collaboration across the various hospitals is critical for successful formulary
      standardization. When implementing a health-system P&T committee or standardizing
      a formulary system, it is important to be patient and give local sites time to
      make practice changes. Evidence-based data and rationale must be provided to all
      sites to support formulary changes. Finally, there must be multidisciplinary
      collaboration. CONCLUSION: There are several options for formulary structures and
      P&T committees in a health system. Potential strengths and barriers should be
      evaluated before selecting a formulary management process.

PMID- 29572314
TI  - Pharmacy informatics in multihospital health systems: Opportunities and
      challenges.
AB  - PURPOSE: Challenges and opportunities in managing pharmacy-related technology in
      a multihospital health system are reviewed. SUMMARY: With electronic medical
      record (EMR) implementations, pharmacy technology deployments, and increased
      numbers of hospitals merging into single health systems, opportunities and
      challenges for pharmacy informatics (PI) teams have grown. Pharmacy leaders must
      consider the implications of using technology in a multihospital health-system
      environment, as well as the impact of the health system's organizational
      structures on technology implementations and dedicated support teams. Common
      challenges in achieving EMR and other technology implementation and
      standardization initiatives in multihospital health systems include harmonization
      of practices across hospitals of various sizes and types and issues of platform
      compatibility and interoperability. PI teams must collaborate with information
      technology teams at the system level to identify practical strategies for making
      the best use of available resources to implement pharmacy automation and software
      to help pharmacists continue to provide safe and effective patient care. The
      organizational structures that affect informatics teams, pharmacy integration and
      standardization initiatives, formulary management practices, data management and
      analytics, and clinical decision support systems all must be areas of focus.
      CONCLUSION: An integrated pharmacy enterprise can be well positioned to leverage
      operational efficiencies gained from appropriate use of technology to enhance
      patient care. Careful attention must be paid to the manner in which these systems
      are designed, implemented, and managed in order to make the best use of the
      technological resources used by the health system.

PMID- 29572315
TI  - Development and innovation of system resources to optimize patient care.
AB  - PURPOSE: Various incremental and disruptive healthcare innovations that are
      occurring or may occur are discussed, with insights on how multihospital health
      systems can prepare for the future and optimize the continuity of patient care
      provided. SUMMARY: Innovation in patient care is occurring at an ever-increasing
      rate, and this is especially true relative to the transition of patients through
      the care continuum. Health systems must leverage their ability to standardize and
      develop electronic health record (EHR) systems and other infrastructure necessary
      to support patient care and optimize outcomes; examples include 3D printing of
      patient-specific medication dosage forms to enhance precision medicine, the use
      of drones for medication delivery, and the expansion of telehealth capabilities
      to improve patient access to the services of pharmacists and other healthcare
      team members. Disruptive innovations in pharmacy services and delivery will alter
      how medications are prescribed and delivered to patients now and in the future.
      Further, technology may also fundamentally alter how and where pharmacists and
      pharmacy technicians care for patients. This article explores the various
      innovations that are occurring and that will likely occur in the future,
      particularly as they apply to multihospital health systems and patient continuity
      of care. CONCLUSION: Pharmacy departments that anticipate and are prepared to
      adapt to incremental and disruptive innovations can demonstrate value in the
      multihospital health system through strategies such as optimizing the EHR,
      identifying telehealth opportunities, supporting infrastructure, and integrating
      services.

PMID- 29572316
TI  - Creating a learning organization to help meet the needs of multihospital health
      systems.
AB  - PURPOSE: The considerations that leaders of multihospital health systems must
      take into account in developing and implementing initiatives to build and
      maintain an exceptional pharmacy workforce are described. SUMMARY: Significant
      changes that require constant individual and organizational learning are
      occurring throughout healthcare and within the profession of pharmacy. These
      considerations include understanding why it is important to have a succession
      plan and determining what types of education and training are important to
      support that plan. Other considerations include strategies for leveraging
      learners, dealing with a large geographic footprint, adjusting training
      opportunities to accommodate the ever-evolving demands on pharmacy staffs in
      terms of skill mix, and determining ways to either budget for or internally
      develop content for staff development. All of these methods are critically
      important to ensuring an optimized workforce. Especially for large health systems
      operating multiple sites across large distances, the use of technology-enabled
      solutions to provide effective delivery of programming to multiple sites is
      critical. Commonly used tools include live webinars, live "telepresence"
      programs, prerecorded programming that is available through an on-demand
      repository, and computer-based training modules. A learning management system is
      helpful to assign and document completion of educational requirements, especially
      those related to regulatory requirements (e.g., controlled substances management,
      sterile and nonsterile compounding, competency assessment). CONCLUSION: Creating
      and sustaining an environment where all pharmacy caregivers feel invested in and
      connected to ongoing learning is a powerful motivator for performance,
      engagement, and retention.

PMID- 29572317
TI  - Designing organizational structures: Key thoughts for development.
AB  - PURPOSE: Current strategies and concepts to consider in developing a system-level
      organizational structure for the pharmacy enterprise are discussed. SUMMARY:
      There are many different ways to design an organizational structure for the
      pharmacy enterprise within a health system. The size of the organization, the
      number of states in which it operates, and the geographic spread and complexity
      of the pharmacy business lines should be among the key considerations in
      determining the optimal organizational and decision-making structures for the
      pharmacy enterprise. The structure needs to support incorporation of the pharmacy
      leadership (both system-level executives and local leaders) into all strategic
      planning and discussions at the hospital and health-system levels so that they
      can directly represent the pharmacy enterprise instead of relying on others to
      develop strategy on their behalf. It is important that leaders of all aspects of
      the pharmacy enterprise report through the system's top pharmacy executive, who
      should be a pharmacist and have a title consistent with those of other leaders
      reporting at the same organizational level (e.g., chief pharmacy officer).
      CONCLUSION: Pharmacy leaders need to be well positioned within an organization to
      advocate for the pharmacy enterprise and use all resources to the best of their
      ability. As the scope and complexity of pharmacy services grow, it is critical to
      ensure that leadership of the pharmacy enterprise is unified under a single
      pharmacy executive team.

PMID- 29572318
TI  - Contraceptive shortages mean Venezuela's people face a sexual health emergency.

PMID- 29572319
TI  - Ossabaw Pigs With a PCSK9 Gain-of-Function Mutation Develop Accelerated Coronary
      Atherosclerotic Lesions: A Novel Model for Preclinical Studies.
AB  - BACKGROUND: Ossabaw pigs are unique miniature swine with genetic predisposition
      to develop metabolic syndrome and coronary atherosclerosis after extended periods
      receiving atherogenic diets. We have hypothesized that transgenic Ossabaw swine
      expressing chimp PCSK9 (proprotein convertase subtilisin-like/kexin type 9)
      containing the D374Y gain of function would develop familial hypercholesterolemia
      and coronary artery plaques more rapidly than Landrace swine with the same
      transgene. METHODS AND RESULTS: Ossabaw and Landrace PCSK9 gain-of-function
      founders were generated by Sleeping Beauty transposition and cloning.
      Histopathologic findings in the Ossabaw founder animal showed more advanced
      plaques and higher stenosis than in the Landrace founder, underscoring the
      Ossabaw genetic predisposition to atherosclerosis. We chose to further
      characterize the Ossabaw PCSK9 gain-of-function animals receiving standard or
      atherogenic diets in a 6-month longitudinal study using computed tomography,
      magnetic resonance (MR) imaging, intravascular ultrasound, and optical coherence
      tomography, followed by pathological analysis of atherosclerosis focused on the
      coronary arteries. The Ossabaw model was consistently hypercholesterolemic, with
      or without dietary challenge, and by 6 months had consistent and diffuse
      fibrofatty or fibroatheromatous plaques with necrosis, overlying fibrous caps,
      and calcification in up to 10% of coronary plaques. CONCLUSIONS: The Ossabaw
      PCSK9 gain-of-function model provides consistent and robust disease development
      in a time frame that is practical for use in preclinical therapeutic evaluation
      to drive innovation. Although no animal model perfectly mimics the human
      condition, this genetic large-animal model is a novel tool for testing
      therapeutic interventions in the context of developing and advanced coronary
      artery disease.

PMID- 29572320
TI  - Decreased cAMP Level and Decreased Downregulation of beta1-Adrenoceptor
      Expression in Therapeutic Hypothermia-Resuscitated Myocardium Are Associated With
      Improved Post-Resuscitation Myocardial Function.
AB  - BACKGROUND: Epinephrine administered during cardiopulmonary resuscitation (CPR)
      is associated with severe post-resuscitation myocardial dysfunction. We
      previously demonstrated that therapeutic hypothermia reduced the severity of post
      resuscitation myocardial dysfunction caused by epinephrine; however, the
      relationship between myocardial adrenoceptor expression and myocardial protective
      effects by hypothermia remains unclear. METHODS AND RESULTS: Rats weighing
      between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo,
      (2) normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic
      epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation).
      Ventricular fibrillation was induced and untreated for 8 minutes for all other
      groups. Hypothermia was initiated coincident with the start of CPR and maintained
      at 33+/-0.2 degrees C for 4 hours. Placebo or epinephrine was administered 5
      minutes after the start of CPR and 3 minutes before defibrillation. Post
      resuscitation ejection fraction was measured hourly for 4 hours then hearts were
      harvested. Epinephrine increased coronary perfusion pressure during CPR (27+/-6
      mm Hg versus 21+/-2 mm Hg P<0.05). Post-resuscitation myocardial function was
      impaired in the normothermic epinephrine group compared with other groups. The
      concentration of myocardial cAMP doubled in the normothermic epinephrine group
      (655.06+/-447.63 MUmol/L) compared with the hypothermic epinephrine group
      (302.51+/-97.98 MUmol/L; P<0.05). Myocardial beta1-adrenoceptor expression
      decreased with normothermia cardiac arrest but not with hypothermia regardless of
      epinephrine. CONCLUSIONS: Epinephrine, administered during normothermic CPR,
      increased the severity of post-resuscitation myocardial dysfunction. This adverse
      effect was inhibited by intra-arrest hypothermia resuscitation. Declined cAMP
      with more preserved beta1-adrenoceptors in hypothermia-resuscitated myocardium is
      associated with improved post-resuscitated myocardial function in vivo.

PMID- 29572321
TI  - Ablation Outcomes and Predictors of Mortality Following Catheter Ablation for
      Ventricular Tachycardia: Data From the German Multicenter Ablation Registry.
AB  - BACKGROUND: Ventricular tachycardia (VT) causes significant morbidity and
      mortality. Implantable cardioverter-defibrillator shocks terminate VT but confer
      a significant morbidity and mortality risk. Therefore, VT ablation is
      increasingly common. Patients with structural heart disease (SHD) and patients
      with structurally normal hearts as well as the subgroup with and without ischemic
      heart disease were assessed for predictors of mortality and nonfatal VT
      recurrence. We present the first multicenter, prospective German VT registry.
      METHODS AND RESULTS: In 334 patients, 118 structurally normal hearts and 216 SHD
      (74.5% ischemic heart disease), referred for VT ablation in 38 centers, long-term
      follow-up was assessed for a minimum of 12 months and analyzed for factors
      predicting VT recurrence rates and mortality. The VTs in SHD patients were more
      frequently hemodynamically unstable (34.7% versus 12.7%, P<0.0001) or incessant
      (9.7% versus 2.7%, P<0.05). More SHD patients underwent substrate modification
      than patients with structurally normal hearts who had more focal ablations.
      Ablation failure was 9% in both groups. Two-year mortality was higher in patients
      with SHD (18.7% versus 3.5%, P<0.001). Predictors of mortality include age >60
      years, incessant VT, left ventricular ejection fraction <=30%, procedural
      failure, and Class I and III anti-arrhythmic drug use at discharge. Only
      procedural failure is a predictor of nonfatal VT recurrence. CONCLUSIONS:
      Procedural failure was the sole independent predictor for nonfatal VT recurrence
      for our study cohort. This emphasizes the importance of a successful ablation
      procedure in experienced hands to reduce long-term mortality and nonfatal VT
      recurrence.

PMID- 29572322
TI  - Sp1 Plays an Important Role in Vascular Calcification Both In Vivo and In Vitro.
AB  - BACKGROUND: Vascular calcification and increased cardiovascular morbidity and
      mortality are closely related in patients with end-stage renal disease and
      diabetes mellitus. Specific protein 1 (Sp1) is a transactivation molecule that
      plays a crucial role in the regulation of apoptosis, fibrosis, angiogenesis, and
      other pathological disorders. There is evidence that specific protein 1 (Sp1)
      directly stimulates the transcription of bone morphogenetic protein 2 (BMP2) and
      that BMP2 plays a key role in the calcification process in the BMP2-expressing F9
      cell model system. Here, we investigated whether Sp1 plays an important role in
      vascular calcification and its potential regulatory mechanism in vascular
      calcification. METHODS AND RESULTS: In this study, vascular calcification was
      induced in male Wistar rats by administration of nicotine (25 mg/kg) and vitamin
      D3 (300 000 IU/kg). These rats were randomly selected for treatment with
      adenovirus harboring Sp1 knockdown gene or empty virus. The mechanism of Sp1 in
      vascular smooth muscle cells cultured in high phosphate medium was studied. Based
      on our findings, the Sp1 gene silencing or inhibition improved calcium
      deposition, which was partly achieved by inhibiting phenotype switch, apoptosis,
      and matrix vesicle release of vascular smooth muscle cells. Moreover, Sp1 can
      activate BMP2 transcription by binding to the Sp1-binding element of the BMP2
      promoter. CONCLUSIONS: Overall, elevated Sp1 exerts a pro-apoptotic effect,
      promoting BMP2 transcription and further accumulating vascular calcification.
      Proper and timely regulation of Sp1 expression may be a potential strategy for
      treatment of aging, end-stage renal disease, and diabetic-related macrovascular
      disease treatment.

PMID- 29572323
TI  - Evaluation of Collateral Source Characteristics With 3-Dimensional Analysis Using
      Micro-X-Ray Computed Tomography.
AB  - BACKGROUND: Collateral arteries provide an alternative blood supply and protect
      tissues from ischemic damage in patients with peripheral artery disease. However,
      the mechanism of collateral artery development is difficult to validate. METHODS
      AND RESULTS: Collateral arteries were visualized using micro-x-ray computed
      tomography. Developmental characteristics were assessed using confocal
      microscopy. We conducted a single-center, retrospective, observational study and
      assessed the dilatation of collateral arteries on ischemic sides. We quantified
      the vascular volume in both ischemic and nonischemic legs. A prominent increase
      in vascular volume was observed in the ischemic leg using a murine hind-limb
      ischemia model. We also performed qualitative assessment and confirmed that the
      inferior gluteal artery functioned as a major collateral source. Serial analysis
      of murine hind-limb vessel development revealed that the inferior gluteal artery
      was a remnant of the ischial artery, which emerged as a representative vessel on
      the dorsal side during hind-limb organogenesis. We retrospectively analyzed
      consecutive patients who were admitted for the diagnosis or treatment of
      peripheral artery disease. The diameter of the inferior gluteal artery on the
      ischemic side showed significant dilatation compared with that on the nonischemic
      side. CONCLUSIONS: Our findings indicate that an embryonic remnant artery can
      become a collateral source under ischemic conditions. Flow enhancement in the
      inferior gluteal artery might become a novel therapeutic approach for patients
      with peripheral artery disease.

PMID- 29572324
TI  - Left Atrial Epicardial Fat Volume Is Associated With Atrial Fibrillation: A
      Prospective Cardiovascular Magnetic Resonance 3D Dixon Study.
AB  - BACKGROUND: Recent studies demonstrated a strong association between atrial
      fibrillation (AF) and epicardial fat around the left atrium (LA). We sought to
      assess whether epicardial fat volume around the LA is associated with AF, and to
      determine the additive value of LA-epicardial fat measurements to LA structural
      remodeling for identifying patients with AF using 3-dimensional multi-echo Dixon
      fat-water separated cardiovascular magnetic resonance. METHODS AND RESULTS: A
      total of 105 subjects were studied: 53 patients with a history of AF and 52 age
      matched patients with other cardiovascular diseases but no history of AF. The 3
      dimensional multi-echo Dixon fat-water separated sequence was performed for LA
      epicardial fat measurements. AF patients had significantly greater LA-epicardial
      fat (28.9+/-12.3 and 14.2+/-7.3 mL for AF and non-AF, respectively; P<0.001) and
      LA volume (110.8+/-38.2 and 89.7+/-30.3 mL for AF and non-AF, respectively;
      P=0.002). LA-epicardial fat adjusted for LA volume was still higher in patients
      with AF compared with those without AF (P<0.001). LA-epicardial fat and
      hypertension were independently associated with the risk of AF (odds ratio, 1.17;
      95% confidence interval, 1.10%-1.25%, P<0.001, and odds ratio, 3.29; 95%
      confidence interval, 1.17%-9.27%, P=0.03, respectively). In multivariable
      logistic regression analysis adjusted for body surface area, LA-epicardial fat
      remained significant and an increase per mL was associated with a 42% increase in
      the odds of AF presence (odds ratio, 1.42; 95% confidence interval, 1.23%-1.62%,
      P<0.001). Combined assessment of LA-epicardial fat and LA volume provided greater
      discriminatory performance for detecting AF than LA volume alone (c
      statistic=0.88 and 0.74, respectively, DeLong test; P<0.001). CONCLUSIONS:
      Cardiovascular magnetic resonance 3-dimensional Dixon-based LA-epicardial fat
      volume is significantly increased in AF patients. LA-epicardial fat measured by 3
      dimensional Dixon provides greater performance for detecting AF beyond LA
      structural remodeling.

PMID- 29572325
TI  - Prevalence, Causes, and Predictors of 30-Day Readmissions Following
      Hospitalization With Acute Myocardial Infarction Complicated By Cardiogenic
      Shock: Findings From the 2013-2014 National Readmissions Database.
AB  - BACKGROUND: Prior studies have shown that survivors of acute myocardial
      infarction (AMI) complicated by cardiogenic shock are likely to have increased
      risk of readmissions in the early post-discharge period. However, the
      contemporary prevalence, reasons, and predictors of 30-day readmissions are not
      well known. METHODS AND RESULTS: Hospitalizations for a primary diagnosis of AMI
      complicated by cardiogenic shock, and discharged alive, were identified in the
      2013 and 2014 Nationwide Readmissions Databases. Prevalence and reasons for 30
      day unplanned readmissions were investigated. A hierarchical logistic regression
      model was used to identify independent predictors of 30-day readmissions. Among 1
      116 933 patient hospitalizations with AMI, 39 807 (3.6%) had cardiogenic shock
      and were discharged alive. Their 30-day readmission rate was 18.6%, with a median
      time for readmission 10 days post discharge. Predictors of readmission included:
      non-ST-segment elevation myocardial infarction, female sex, low-income status,
      nonprivate insurance, chronic renal failure, long-term ventricular assist device
      or intra-aortic balloon placement, and tachyarrhythmia. The majority of
      readmissions were attributable to cardiac-related causes (52%); heart failure
      being the most frequent cardiac cause (39% of all cardiac causes). Noncardiac
      related readmissions included infections (14.9%), bleeding (5.3%), and
      respiratory causes (4.9%). The median cost per readmission was $9473 US dollars
      ($5037-20 199). CONCLUSIONS: Among survivors of AMI complicated by cardiogenic
      shock who were discharged from hospital, almost 1 in 5 are readmitted at 30 days,
      mainly because of cardiac reasons such as heart failure and new AMI. The risk of
      readmission was associated with certain baseline patient/hospital
      characteristics.

PMID- 29572326
TI  - Fuzzy and fast nuclear transport.
AB  - Exchange of macromolecules between the cytoplasm and the nucleus of all
      eukaryotic cells is controlled by nuclear pore complexes, which form a selective
      permeability barrier. The requirement for rapid but selective transport leads to
      a "transport paradox." A new experimental study now provides a thermodynamic
      explanation.

PMID- 29572327
TI  - A new actin-binding domain glues autophagy together.
AB  - Autophagy breaks down nonessential cellular components to replenish
      macromolecular building blocks during starvation. Nevertheless, the downstream
      events regulating vesicle trafficking during this essential cellular process are
      not yet fully defined. Xu et al. combined approaches of crystallography,
      biochemistry, and cell biology to show that the guanine nucleotide exchange
      factor DENND3 contains an actin-binding site they call "PHenn domain" in a region
      previously thought to be unstructured. PHenn domain binding to microfilaments is
      necessary for DENND3's participation in autophagy, providing a new link between
      autophagic stimulation and actin microfilaments. The findings by Xu et al. shed
      important new light on how membrane trafficking participates in critical steps of
      autophagy in relationship with actin microfilaments.

PMID- 29572328
TI  - Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and
      action in pancreatic beta cells.

PMID- 29572329
TI  - Distinct differences in prion-like seeding and aggregation between Tau protein
      variants provide mechanistic insights into tauopathies.

PMID- 29572330
TI  - A novel chemical inducer of Streptococcus quorum sensing acts by inhibiting the
      pheromone-degrading endopeptidase PepO.

PMID- 29572331
TI  - A novel topology of proline-rich transmembrane protein 2 (PRRT2): Hints for an
      intracellular function at the synapse.

PMID- 29572332
TI  - Structural Studies of Multidrug Resistance Protein 1 Using "Almost" Cysless
      Template.
AB  - Multidrug resistance protein, MRP1 (ABCC1) is a broad-spectrum ATP-binding
      cassette transporter that plays a major role in defense against dietary and
      environmental toxicants, in addition to contributing toward multidrug resistance
      of certain types of malignancy. Elucidating the molecular structure of hMRP1 is
      key to determining its mechanism of substrate recognition and transport. Here, we
      report the first successful attempt using cysteine-scanning mutagenesis coupled
      with cross-linking studies to probe the structure of hMRP1 in its native
      environment of the cell membrane or in membrane vesicles. We have established
      that an active 3Cys DeltaMRP1 (MRP204-1531) mutant, described in previous studies
      from our laboratory, is a suitable template with which to generate single- and
      double-cysteine mutants for performing cysteine mutagenesis studies. We have now
      used 3Cys DeltaMRP1 to probe the arrangement of several TM segments, as well as
      the location of individual amino acids in these regions. Cysteine residues were
      introduced into TMs 8, 14, 15, and 16 of 3Cys DeltaMRP1. The mutants were then
      subjected to chemical cross-linking analyses, and cross-linking was detected
      between the following cysteine pairs: Cys388 (TM7) and I1193C (TM16); Cys388
      (TM7) and E1144C (TM15); R433C (TM8) and E1144C (TM15); and R433C (TM8) and
      T1082C (TM14). The aqueous accessibility of these residues and the possible
      implications of the differences between the open and closed states of the protein
      are also discussed. Moreover, using competition experiments involving a well
      characterized substrate and a cross-linking reagent for probing the Cys388/
      I1193C mutant, we have defined these amino acid positions as a component of the
      potential site for estrone sulfate binding.

PMID- 29572333
TI  - Risk of Clinically Relevant Pharmacokinetic-Based Drug-Drug Interactions with
      Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.
AB  - A total of 103 drugs (including 14 combination drugs) were approved by the U.S.
      Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug
      interaction profiles were analyzed using the University of Washington Drug
      Interaction Database, and the clinical relevance of these observations was
      characterized based on information from new drug application reviews. CYP3A was
      involved in approximately two-thirds of all drug-drug interactions (DDIs).
      Transporters (alone or with enzymes) participated in about half of all
      interactions, but most of these were weak-to-moderate interactions. When
      considered as victims, eight new molecular entities (NMEs; cobimetinib,
      ibrutinib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and
      venetoclax) were identified as sensitive substrates of CYP3A, two NMEs
      (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME
      (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a
      sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive
      substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when
      coadministered with a strong inhibitor). Approximately 75% of identified CYP3A
      substrates were also substrates of P-glycoprotein. As perpetrators, most clinical
      DDIs involved weak-to-moderate inhibition or induction. Only idelalisib showed
      strong inhibition of CYP3A, and lumacaftor behaved as a strong CYP3A inducer.
      Among drugs with large changes in exposure (>=5-fold), whether as victim or
      perpetrator, the most-represented therapeutic classes were antivirals and
      oncology drugs, suggesting a significant risk of clinical DDIs in these patient
      populations.

PMID- 29572334
TI  - Expert consensus regarding drivers of antimicrobial stewardship in companion
      animal veterinary practice: a Delphi study.
AB  - Antimicrobial resistance (AMR) is a global challenge facing both human and animal
      healthcare professionals; an effective response to this threat requires a 'One
      Health' approach to antimicrobial stewardship (AMS) to preserve important
      antibiotics for urgent clinical need. However, understanding of barriers and
      enablers to effective AMS behaviour in companion animal veterinary practice is
      currently limited. We conducted a Delphi study of 16 nationally recognised
      experts from UK-based veterinary policymakers, university academics and leaders
      of professional bodies. This Delphi study sought to identify veterinary
      behaviours which experts believe contribute to AMR and form vital aspects of AMS.
      Analysis of Delphi findings indicated a perceived hierarchy of behaviours, the
      most influential being antibiotic prescribing behaviours and interactions with
      clients. Other veterinary behaviours perceived as being important related to
      interactions with veterinary colleagues; infection control practices; and the use
      of diagnostic tests to confirm infection. Key barriers and enablers to AMS within
      each of these behavioural domains were identified. Specific interventions to
      address important barriers and enablers are recommended. To the authors'
      knowledge, this is the first study to establish expert consensus at a national
      level about which 'behaviours' (aspects of veterinarian practice) should be
      targeted in relation to AMR and AMS in companion animal veterinary practice.

PMID- 29572335
TI  - Effect of horse sex status on British Eventing competition performance: an
      observational study between 1998 and 2016.
AB  - To test the hypothesis that gender affects horse scores in eventing competition,
      data on the scores and points awarded to 681 horses was collected from the
      British Eventing website. Equal numbers of mares, geldings and stallions were
      used, all foaled during or after 1994 and aged 4-10 years. The study included
      five levels of competition (BE90, BE100, Novice, Intermediate and Advanced) and
      investigated differences in mean phased scores, total scores and rank in
      competition. Additionally, the mean and median 'BE points per competition' of
      each gender were compared. Significant differences in performance between genders
      were found at all levels except Advanced. Differences were highlighted in average
      phased and total scores, rank and median points per competition. There was an
      overall pattern of stallions and geldings outperforming mares, though this was
      not found to be true at all levels. The only area in which mares were found to
      perform significantly better than geldings or stallions was showjumping time
      penalties at BE90.

PMID- 29572336
TI  - GPR40-Mediated Galpha12 Activation by Allosteric Full Agonists Highly Efficacious
      at Potentiating Glucose-Stimulated Insulin Secretion in Human Islets.
AB  - GPR40 is a clinically validated molecular target for the treatment of diabetes.
      Many GPR40 agonists have been identified to date, with the partial agonist
      fasiglifam (TAK-875) reaching phase III clinical trials before its development
      was terminated due to off-target liver toxicity. Since then, attention has
      shifted toward the development of full agonists that exhibit superior efficacy in
      preclinical models. Full agonists bind to a distinct binding site, suggesting
      conformational plasticity and a potential for biased agonism. Indeed, it has been
      suggested that alternative pharmacology may be required for meaningful efficacy.
      In this study, we described the discovery and characterization of Compound A, a
      newly identified GPR40 allosteric full agonist highly efficacious in human islets
      at potentiating glucose-stimulated insulin secretion. We compared Compound A
      induced GPR40 activity to that induced by both fasiglifam and AM-1638, another
      allosteric full agonist previously reported to be highly efficacious in
      preclinical models, at a panel of G proteins. Compound A was a full agonist at
      both the Galphaq and Galphai2 pathways, and in contrast to fasiglifam Compound A
      also induced Galpha12 coupling. Compound A and AM-1638 displayed similar activity
      at all pathways tested. The Galpha12/Galpha13-mediated signaling pathway has been
      linked to protein kinase D activation as well as actin remodeling, well known to
      contribute to the release of insulin vesicles. Our data suggest that the
      pharmacology of GPR40 is complex and that Galpha12/Galpha13-mediated signaling,
      which may contribute to GPR40 agonists therapeutic efficacy, is a specific
      property of GPR40 allosteric full agonists.

PMID- 29572338
TI  - Institute of Medical Ethics Guidelines for confirmation of appointment, promotion
      and recognition of UK bioethics and medical ethics researchers.
AB  - This document is designed to give guidance on assessing researchers in
      bioethics/medical ethics. It is intended to assist members of selection,
      confirmation and promotion committees, who are required to assess those
      conducting bioethics research when they are not from a similar disciplinary
      background. It does not attempt to give guidance on the quality of bioethics
      research, as this is a matter for peer assessment. Rather it aims to give an
      indication of the type, scope and amount of research that is the expected in this
      field. It does not cover the assessment of other activities such as teaching,
      policy work, clinical ethics consultation and so on, but these will be mentioned
      for additional context. Although it mentions the UK's Research Excellence
      Framework (REF), it is not intended to be a detailed analysis of the place of
      bioethics in the REF.

PMID- 29572339
TI  - Montgomery, informed consent and causation of harm: lessons from Australia or a
      uniquely English approach to patient autonomy?
AB  - The UK Supreme Court in Montgomery v Lanarkshire Health Board adopts an approach
      to information disclosure in connection with clinical treatment that moves away
      from medical paternalism towards a more patient-centred approach. In doing so, it
      reinforces the protection afforded to informed consent and autonomous patient
      decision making under the law of negligence. However, some commentators have
      expressed a concern that the widening of the healthcare providers' duty of
      disclosure may provide impetus, in future cases, for courts to adopt a more
      rigorous approach to the application of causation principles. The aim would be to
      limit liability but, in turn, it would also limit autonomy protection. Such a
      restrictive approach has recently been adopted in Australia as a result of the
      High Court decision in Wallace v Kam This paper considers whether such an
      approach is likely under English negligence law and discusses case law from both
      jurisdictions in order to provide a point of comparison from which to scope the
      post-Montgomery future.

PMID- 29572337
TI  - Palliative radiotherapy.

PMID- 29572340
TI  - Gift of creativity with Parkinson's disease.

PMID- 29572341
TI  - In Vitro Assessment of Pharmacokinetic Drug-Drug Interactions of Direct Oral
      Anticoagulants: Type 5-Phosphodiesterase Inhibitors Are Inhibitors of Rivaroxaban
      and Apixaban Efflux by P-Glycoprotein.
AB  - Because of their lower bleeding risk and simplicity of use, direct oral
      anticoagulants (DOACs) could represent an interesting alternative to conventional
      anticoagulant treatment with vitamin K antagonists for patients with pulmonary
      arterial hypertension (PAH). P-glycoprotein (P-gp) plays a key role in DOAC
      pharmacokinetics. Type 5-phosphodiesterase inhibitors (PDE5is), a drug class
      commonly used in the treatment of PAH, have been shown to strongly inhibit P-gp.
      This work aimed to assess potential P-gp-mediated drug-drug interactions between
      PDE5is and DOACs using in vitro methods. A cellular model of drug transport
      assay, using P-gp-overexpressing Madin-Darby canine kidney cells (transfected
      with the human P-gp gene), was used to determine the bidirectional permeabilities
      of two DOACs (rivaroxaban and apixaban) in the absence and presence of increasing
      concentrations (0.5-100 uM) of three PDE5is (sildenafil, tadalafil, and
      vardenafil). Permeabilities and efflux ratios were calculated from DOAC
      concentrations, were measured with liquid chromatography coupled with mass
      spectrometry, and were subsequently used to determine the PDE5i percentage of
      inhibition and half maximal inhibitory concentration (IC50 ). Rivaroxaban efflux
      was inhibited by 99%, 66%, and 100% with 100 uM sildenafil, tadalafil, and
      vardenafil, respectively. Similarly, apixaban efflux was inhibited by 97%, 74%,
      and 100%, respectively. The IC50 values of the three PDE5is were 8, 28, and 5 uM
      for rivaroxaban and 23, 15, and 3 uM for apixaban, respectively. This study
      showed strong in vitro inhibition of DOAC efflux by PDE5is. In vivo studies are
      required to determine the clinical relevance of these interactions.

PMID- 29572342
TI  - Protectin DX Ameliorates Hepatic Steatosis by Suppression of Endoplasmic
      Reticulum Stress via AMPK-Induced ORP150 Expression.
AB  - Docosahexaenoic acid (DHA) and its bioactive compounds may have suppressive
      effects on inflammation, endoplasmic reticulum (ER) stress, and insulin
      resistance. Protectin DX (PDX), a double lipoxygenase product from DHA has shown
      a suppressive effect on inflammation and insulin resistance. However, the effects
      of PDX on ER stress and hepatic steatosis have not been elucidated yet. Herein we
      report that PDX could stimulate the AMP-activated protein kinase (AMPK)
      phosphorylation, thereby upregulating oxygen-regulated protein 150 (ORP150)
      expression in a dose-dependent manner. Treatment of HepG2 cells with PDX
      attenuated the palmitate-induced triglyceride accumulation through regulation of
      the sterol regulatory element-binding protein 1 (SREBP1)-mediated pathway. To
      deal with the pharmacological significance in the protective effects of PDX on
      hepatic steatosis, we performed in vivo experiments. In a mouse model, the PDX
      administration would alleviate the high-fat diet-induced hepatic steatosis and
      trigger the hepatic AMPK phosphorylation and ORP150 expression. PDX improved
      palmitate-induced and HFD-induced impairment of hepatic lipid metabolism and
      steatosis through suppression of ER stress via an AMPK-ORP150-dependent pathway.

PMID- 29572343
TI  - Nature-based supportive care opportunities: a conceptual framework.
AB  - OBJECTIVE: Given preliminary evidence for positive health outcomes related to
      contact with nature for cancer populations, research is warranted to ascertain
      possible strategies for incorporating nature-based care opportunities into
      oncology contexts as additional strategies for addressing multidimensional
      aspects of cancer patients' health and recovery needs. The objective of this
      study was to consolidate existing research related to nature-based supportive
      care opportunities and generate a conceptual framework for discerning relevant
      applications in the supportive care setting. METHODS: Drawing on research
      investigating nature-based engagement in oncology contexts, a two-step analytic
      process was used to construct a conceptual framework for guiding nature-based
      supportive care design and future research. Concept analysis methodology
      generated new representations of understanding by extracting and synthesising
      salient concepts. Newly formulated concepts were transposed to findings from
      related research about patient-reported and healthcare expert-developed
      recommendations for nature-based supportive care in oncology. RESULTS: Five
      theoretical concepts (themes) were formulated describing patients' reasons for
      engaging with nature and the underlying needs these interactions address. These
      included: connecting with what is genuinely valued, distancing from the cancer
      experience, meaning-making and reframing the cancer experience, finding comfort
      and safety, and vital nurturance. Eight shared patient and expert recommendations
      were compiled, which address the identified needs through nature-based
      initiatives. Eleven additional patient-reported recommendations attend to
      beneficial and adverse experiential qualities of patients' nature-based
      engagement and complete the framework. CONCLUSIONS: The framework outlines
      salient findings about helpful nature-based supportive care opportunities for
      ready access by healthcare practitioners, designers, researchers and patients
      themselves.

PMID- 29572344
TI  - Advance care planning: the impact of Ceiling of Treatment plans in patients with
      Coordinate My Care.
AB  - OBJECTIVES: The aim of this evaluation is to describe the components and results
      of urgent care planning in Coordinate My Care (CMC), a digital clinical service
      for patients with life-limiting illness, for use if a patient is unable to make
      or express choices. Ceiling of treatment (CoT) plans were created detailing where
      the patient would like to receive their care and how aggressive medical
      interventions should be. METHODS: A retrospective service evaluation was
      completed of all CMC records created between December 2015 and September 2016
      (n=6854). CMC records were divided into two cohorts: those with a CoT plan and
      those without. The factors associated with these cohorts were reviewed including
      age, diagnosis, resuscitation status and preferences for place of death (PPD).
      Analysis of the non-mandatory free text section was carried out. RESULTS: Two
      thirds of patients had recorded decisions about CoT. Regardless of which CoT
      option was chosen, for most patients, PPD was home or care home. Patients with a
      CoT plan were more likely to have a documented resuscitation status.Patients with
      a CoT were more likely to die in their PPD (82%vs71%, OR 1.79, p<0.0001). A
      higher proportion of patients with a CoT decision died outside hospital.
      CONCLUSION: This analysis demonstrates that a substantial proportion of patients
      are willing to engage in urgent care planning. Three facets of urgent care
      planning identified include PPD, CoT and resuscitation status.

PMID- 29572345
TI  - Does being overweight contribute to longer survival rates in myelodysplastic
      syndrome?

PMID- 29572346
TI  - CD83 in Hodgkin lymphoma.

PMID- 29572347
TI  - Bendamustine plus rituximab in chronic lymphocytic leukemia: is there life in the
      old dog yet?

PMID- 29572348
TI  - Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan
      Interactions Reduce Leukocyte Migration and Disease Severity in a Model of
      Rheumatoid Arthritis.
AB  - Inflammation is characterized by the infiltration of leukocytes from the
      circulation and into the inflamed area. Leukocytes are guided throughout this
      process by chemokines. These are basic proteins that interact with leukocytes to
      initiate their activation and extravasation via chemokine receptors. This is
      enabled through chemokine immobilization by glycosaminoglycans (GAGs) at the
      luminal endothelial surface of blood vessels. A specific stretch of basic amino
      acids on the chemokine, often at the C terminus, interacts with the negatively
      charged GAGs, which is considered an essential interaction for the chemokine
      function. Short-chain peptides based on this GAG-binding region of the chemokines
      CCL5, CXCL8, and CXCL12gamma were synthesized using standard Fmoc chemistry.
      These peptides were found to bind to GAGs with high affinity, which translated
      into a reduction of leukocyte migration across a cultured human endothelial
      monolayer in response to chemokines. The leukocyte migration was inhibited upon
      removal of heparan sulfate from the endothelial surface and was found to reduce
      the ability of the chemokine and peptide to bind to endothelial cells in binding
      assays and to human rheumatoid arthritis tissue. The data suggest that the
      peptide competes with the wild-type chemokine for binding to GAGs such as HS and
      thereby reduces chemokine presentation and subsequent leukocyte migration.
      Furthermore, the lead peptide based on CXCL8 could reduce the disease severity
      and serum levels of the proinflammatory cytokine TNF-alpha in a murine Ag-induced
      arthritis model. Taken together, evidence is provided for interfering with the
      chemokine-GAG interaction as a relevant therapeutic approach.

PMID- 29572349
TI  - Astrocytic glycogen metabolism in the healthy and diseased brain.
AB  - The brain contains a fairly low amount of glycogen, mostly located in astrocytes,
      a fact that has prompted the suggestion that glycogen does not have a significant
      physiological role in the brain. However, glycogen metabolism in astrocytes is
      essential for several key physiological processes and is adversely affected in
      disease. For instance, diminished ability to break down glycogen impinges on
      learning, and epilepsy, Alzheimer's disease, and type 2 diabetes are all
      associated with abnormal astrocyte glycogen metabolism. Glycogen metabolism
      supports astrocytic K+ and neurotransmitter glutamate uptake and subsequent
      glutamine synthesis-three fundamental steps in excitatory signaling at most brain
      synapses. Thus, there is abundant evidence for a key role of glycogen in brain
      function. Here, we summarize the physiological brain functions that depend on
      glycogen, discuss glycogen metabolism in disease, and investigate how glycogen
      breakdown is regulated at the cellular and molecular levels.

PMID- 29572350
TI  - Gain-of-function mutations in granulocyte colony-stimulating factor receptor
      (CSF3R) reveal distinct mechanisms of CSF3R activation.
AB  - Granulocyte colony-stimulating factor (G-CSF or CSF3) and its receptor CSF3R
      regulate granulopoiesis, neutrophil function, and hematopoietic stem cell
      mobilization. Recent studies have uncovered an oncogenic role of mutations in the
      CSF3R gene in many hematologic malignancies. To find additional CSF3R mutations
      that give rise to cell transformation, we performed a cellular transformation
      assay in which murine interleukin 3 (IL-3)-dependent Ba/F3 cells were transduced
      with WT CSF3R plasmid and screened for spontaneous growth in the absence of IL-3.
      Any outgrowth clones were sequenced to identify CSF3R mutations with
      transformation capacity. We identified several novel mutations and determined
      that they transform cells via four distinct mechanisms: 1) cysteine- and
      disulfide bond-mediated dimerization (S581C); 2) polar, noncharged amino acid
      substitution at the transmembrane helix dimer interface at residue Thr-640; 3)
      increased internalization by a Glu-524 substitution that mimics a low G-CSF dose;
      and 4) hydrophobic amino acid substitutions in the membrane-proximal residues Thr
      612, Thr-615, and Thr-618. Furthermore, the change in signaling activation was
      related to an altered CSF3R localization. We also found that CSF3R-induced STAT3
      and ERK activations require CSF3R internalization, whereas STAT5 activation
      occurred at the cell surface. Cumulatively, we have expanded the regions of the
      CSF3R extracellular and transmembrane domains in which missense mutations exhibit
      leukemogenic capacity and have further elucidated the mechanistic underpinnings
      that underlie altered CSF3R expression, dimerization, and signaling activation.

PMID- 29572352
TI  - Ictal pouting: kabuki visage or chapeau de gendarme?

PMID- 29572351
TI  - Interleukin-25 (IL-25) has a protective role in atherosclerosis development in
      the aortic arch in mice.
AB  - Atherosclerosis is a chronic inflammatory disease characterized by the entrapment
      of apolipoprotein B-containing lipoproteins in the arterial intima, leading to
      local inflammation. T helper (Th) cell 1-mediated immune responses have been
      associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL
      17E) has been reported to potentially regulate Th1 cell- and Th17 cell-related
      immune responses. In this study, we evaluated the effects of complete IL-25
      deficiency or of a temporal IL-25 blockade on atherosclerosis development in
      apolipoprotein E-deficient (Apoe-/-) mice. Mice deficient in both apolipoprotein
      E and IL-25 (Apoe-/-/IL-25-/-) had more Th1 cells in the spleen, along with
      elevated plasma levels of IL-17 and an increased release of splenic interferon
      gamma (INF-gamma). In support of this observation, a 4-week-long treatment of
      young Apoe-/- mice (at 10-14 weeks of age) with an IL-25-blocking antibody
      increased the release of Th1/Th17-associated cytokines in the spleen. In both
      mouse models, these findings were associated with increased atherosclerotic
      plaque formation in the aortic arch. We conclude that complete IL-25 deficiency
      and a temporal IL-25 blockade during early plaque development aggravate
      atherosclerosis development in the aortic arch of Apoe-/- mice, accompanied by an
      increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25
      has an atheroprotective role in the murine aortic arch has potential implications
      for atherosclerosis development and management in humans.

PMID- 29572353
TI  - Remember the retina: retinal disorders presenting to neurologists.
AB  - General neurologists and stroke specialists are regularly referred cases of
      visual disturbance by general practitioners, emergency doctors and even
      ophthalmologists. Particularly when the referral comes from ophthalmologists, our
      assessment tends to focus on the optic nerve; however, retinal conditions may
      mimic optic neuropathy and are easily missed. Their diagnosis requires specific
      investigations that are rarely available in a neurology clinic. This article
      focuses on how a general neurologist can identify retinal problems from the
      clinical assessment and how to proceed with initial investigations. The following
      cases were all referred to a consultant neurologist (GTP) from ophthalmology
      services as optic neuropathies or other neurological disorders. Part A of the
      summary describes the presentation and findings in the neurology clinic; part B
      describes the subsequent specialist assessment in the neuro-ophthalmology/eye
      clinic.

PMID- 29572354
TI  - Neurological letter from Chad.

PMID- 29572355
TI  - Vape Factor Fast Find-Adult (VF3-A): a prototype survey method for recording
      brand-specific vaping factors in adult populations.
AB  - BACKGROUND: In population studies, vaping is often treated as a dichotomous
      exposure (present/absent) without consideration of specific vaping devices and
      materials being used. A survey instrument is needed to record specific vaping
      devices and materials. METHODS: We developed a database of 613 vaping device
      models and 3196 vaping liquid products, indexed by device brand, device type,
      liquid brand, liquid name and liquid flavour type. We developed a survey
      instrument to allow participants to report their vaping device and liquid from
      the indexed lists. The survey was pilot tested with a convenience sample of 208
      adults (>=age 21). We validated the vaping device and liquid responses with a
      recontact survey. We report the proportion of respondents finding their products,
      characteristics of people finding their products and survey response times.
      RESULTS: Devices used most frequently in the past 30 days were electronic
      cigarettes (33% of respondents), vaping pens (28%) and vaping mods (16%). Fifty
      seven per cent used liquids containing nicotine most frequently in the past 30
      days, followed by liquids without nicotine (20%) and marijuana or hashish (10%).
      Most (85%) participants found their vaping device successfully (median 19.7 s)
      and 74% found their vaping liquid (median 19.8 s). Females and older adults were
      less likely to find their devices and liquids. Responses were validated for 91%
      and 76% of devices and e-liquids, respectively. CONCLUSIONS: This study
      demonstrated the feasibility of an internet-based survey instrument to record
      specific vaping factors for use in studies of vaping and health.

PMID- 29572356
TI  - MEPs devise strategy to tackle vaccine hesitancy among public.

PMID- 29572357
TI  - BMA and government reach agreement on doctors' bonus scheme.

PMID- 29572358
TI  - Genomics-an aid to diagnosis not a replacement.

PMID- 29572359
TI  - Mapping transcription factor occupancy using minimal numbers of cells in vitro
      and in vivo.
AB  - The identification of transcription factor (TF) binding sites in the genome is
      critical to understanding gene regulatory networks (GRNs). While ChIP-seq is
      commonly used to identify TF targets, it requires specific ChIP-grade antibodies
      and high cell numbers, often limiting its applicability. DNA adenine
      methyltransferase identification (DamID), developed and widely used in
      Drosophila, is a distinct technology to investigate protein-DNA interactions.
      Unlike ChIP-seq, it does not require antibodies, precipitation steps, or chemical
      protein-DNA crosslinking, but to date it has been seldom used in mammalian cells
      due to technical limitations. Here we describe an optimized DamID method coupled
      with next-generation sequencing (DamID-seq) in mouse cells and demonstrate the
      identification of the binding sites of two TFs, POU5F1 (also known as OCT4) and
      SOX2, in as few as 1000 embryonic stem cells (ESCs) and neural stem cells (NSCs),
      respectively. Furthermore, we have applied this technique in vivo for the first
      time in mammals. POU5F1 DamID-seq in the gastrulating mouse embryo at 7.5 d post
      coitum (dpc) successfully identified multiple POU5F1 binding sites proximal to
      genes involved in embryo development, neural tube formation, and mesoderm-cardiac
      tissue development, consistent with the pivotal role of this TF in post
      implantation embryo. This technology paves the way to unprecedented investigation
      of TF-DNA interactions and GRNs in specific cell types of limited availability in
      mammals, including in vivo samples.

PMID- 29572361
TI  - Systemic inflammation and suicide risk: cohort study of 419 527 Korean men and
      women.
AB  - BACKGROUND: Data from only one study have been used to examine the relationship
      between systemic inflammation and later suicide risk, and a strong positive
      association was apparent. More research is needed, particularly looking at
      gender, not least because women are seemingly more vulnerable to inflammation
      induced mood changes than men. METHODS: The Korean Cancer Prevention Study had a
      cohort of over 1 million individuals aged 30-95 years at baseline examination
      between 1992 and 1995, when white blood cell count, our marker of systemic
      inflammation, was assessed. RESULTS: A mean of 16.6 years of mortality
      surveillance gave rise to 1010 deaths from suicide in 106 643 men, and 1019
      deaths from suicide in 312 884 women. There was little evidence of an association
      between our inflammation marker and suicide mortality in men after multiple
      adjustments. In women, however, those in the second inflammation quartile and
      higher experienced around 30% increase risk of death (HR 1.35; 95% CI: 1.11
      1.64). CONCLUSIONS: Higher levels of systemic inflammation were moderately
      related to an elevated risk of suicide death in women but not in men.

PMID- 29572362
TI  - Diffusion-weighted imaging is helpful in the accurate non-invasive diagnosis of
      breast abscess: correlation with necrotic breast cancer.
AB  - Clinical differentiation of atypical breast abscesses from necrotic tumour in
      premenopausal women is challenging and may delay appropriate therapy. In this
      case report, we present a 36-year-old woman with signs, symptoms and conventional
      imaging features of malignancy who underwent breast MRI. On diffusion-weighted
      imaging (DWI), profoundly low apparent diffusion coefficient values were a
      distinguishing sign of breast abscess from necrotic breast cancer, and helped
      manage the patient conservatively. We present a companion case of necrotic breast
      tumour highlighting significant differences in DWI.

PMID- 29572360
TI  - Altered compensatory cytokine signaling underlies the discrepancy between Flt3-/-
      and Flt3l-/- mice.
AB  - The receptor Flt3 and its ligand Flt3L are both critical for dendritic cell (DC)
      development, but DC deficiency is more severe in Flt3l-/- mice than in Flt3-/-
      mice. This has led to speculation that Flt3L binds to another receptor that also
      supports DC development. However, we found that Flt3L administration does not
      generate DCs in Flt3-/- mice, arguing against a second receptor. Instead, Flt3-/-
      DC progenitors matured in response to macrophage colony-stimulating factor (M
      CSF) or stem cell factor, and deletion of Csf1r in Flt3-/- mice further reduced
      DC development, indicating that these cytokines could compensate for Flt3.
      Surprisingly, Flt3-/- DC progenitors displayed enhanced M-CSF signaling,
      suggesting that loss of Flt3 increased responsiveness to other cytokines. In
      agreement, deletion of Flt3 in Flt3l-/- mice paradoxically rescued their severe
      DC deficiency. Thus, multiple cytokines can support DC development, and the
      discrepancy between Flt3-/- and Flt3l-/- mice results from the increased
      sensitivity of Flt3-/- progenitors to these cytokines.

PMID- 29572363
TI  - Central congenital hypothyroidism caused by maternal thyrotoxicosis.
AB  - Central congenital hypothyroidism (CCH) is a rare and underdiagnosed disease that
      sometimes is caused by maternal Graves' disease. We report a case of CCH caused
      by undiagnosed, initially antibody-negative maternal thyrotoxicosis with possible
      disruption of fetal hypothalamic-pituitary-thyroid axis maturation. In CCH,
      maternal thyroid disease should be considered.

PMID- 29572364
TI  - Testicular torsion in a patient with Ehlers-Danlos syndrome.
AB  - We present a 19-year-old man with a diagnosis of Ehlers-Danlos syndrome (EDS) and
      a delayed presentation of testicular torsion. EDS is a rare and heterogeneous
      condition affecting collagen synthesis and presents multiple difficulties in a
      surgical setting. Management of this case of testicular torsion was complicated
      by impaired cognition of the patient, difficulty with intubation, a contralateral
      undescended testis and postoperative bleeding. We discuss the specific challenges
      faced in this case of testicular torsion with longstanding ischaemia and
      perioperative considerations of EDS.

PMID- 29572365
TI  - A rare presentation of haematuria: hip prosthesis in the bladder.
AB  - An 80-year-old woman presented to our department with visible haematuria and
      stage II acute kidney injury (AKI). She had stage IIB cervical cancer, for which
      she received chemotherapy and external beam radiotherapy in 2003. Four years
      later, she had a left dynamic hip screw for an extracapsular neck of femur
      fracture following a fall. In 2010, she underwent a right total hip replacement
      owing to osteoarthritis, and it was subsequently revised in 2012 owing to a right
      acetabular component failure. In this admission, her AKI improved with
      intravenous fluid administration and her haematuria settled following
      catheterisation with a three-way catheter and bladder irrigation with saline. She
      underwent a flexible cystoscopy which revealed that a part of her right hip
      prosthesis was in the bladder, having eroded through the right bony pelvis.
      However, she declined any surgical interventions.

PMID- 29572366
TI  - Importance of source images of time-of-flight magnetic resonance angiography in
      the diagnosis of low-flow dural arteriovenous fistulae after traumatic brain
      injury.
AB  - Three-dimensional time-of-flight (TOF) magnetic resonance angiography (MRA) can
      reliably detect dural arteriovenous fistula (dAVF); however, TOF source images
      should be checked in cases with low-flow dAVFs. A 69-year-old woman reported
      intractable pulsatile tinnitus after head trauma. It was difficult to diagnose
      dAVF using conventional MRA, but it was confirmed using a TOF source image.
      Cerebral angiography revealed a dAVF with a small shunted pouch draining into the
      sigmoid sinus, accompanying the arterial jet flow. Transarterial embolisation of
      the shunted pouch completely obliterated the dAVF. The patient's tinnitus
      immediately disappeared after embolisation. This case suggests that a low-flow
      Borden type I dAVF is undetectable using conventional MRA, and we emphasise the
      importance of evaluating TOF source images. Transarterial embolisation of the
      shunted pouch while preserving the normal sinus flow was safe and effective.

PMID- 29572367
TI  - Myocarditis secondary to smallpox vaccination.
AB  - The development of vaccines ushered in the most profound advancement in 20th
      century medicine, and have widely been regarded as the one of the most important
      scientific discovery in the history of mankind. However, vaccines are not without
      risk; reactions can range from injection site reactions to life-threatening
      anaphylaxis. Among the more serious vaccine-related sequela is myocarditis.
      Although myocarditis has been reported following many different vaccines, the
      smallpox vaccine has the strongest association. We report a case of a 36-year-old
      active duty service member presenting with progressive dyspnoea, substernal chest
      pain and lower extremity swelling 5 weeks after receiving the vaccinia
      vaccination. The aetiology of his acute decompensated heart failure was
      determined to be from myocarditis. Although the majority of cases of myocarditis
      resolve completely, some patients develop chronic heart failure and even death.
      Vaccine-associated myocarditis should always be on the differential for patients
      that exhibit cardiopulmonary symptoms after recent vaccinations.

PMID- 29572368
TI  - Complication of intraprosthetic dislocation of dual-mobility hip implant
      following closed reduction.
AB  - Total hip replacement is a successful operation for the management of hip pain
      but there are potential complications, of which dislocation is one of the most
      common. The management of recurrent dislocation is a challenging problem that
      requires a multimodal approach and the use of dual-mobility implants is one
      option. We present a patient who was previously revised with a dual-mobility
      implant for recurrent dislocation, who had a complication after closed reduction
      of a subsequent intraprosthetic dislocation. Following a missed radiographical
      diagnosis, the patient experienced mechanical symptoms on hip flexion caused by a
      disassociated dual-mobility implant. Subsequent surgical removal of the failed
      implant and revision was required. Careful study of radiographs revealed an
      eccentric femoral head and evidence of the disassociated implant within the
      surrounding soft tissues. Radiographs following closed reduction of
      intraprosthetic dislocations should be scrutinised closely to detect implant
      failure to prevent further complications.

PMID- 29572369
TI  - Rhinofacialentomophthoromycosis.
AB  - Entomopthoromycosis is a rare subcutaneous fungal infection caused by onidiobolus
      coronatus affecting mainly the upper respiratory mucosa in immunocompetent
      people.The manifestations of this disease masquerades other clinical
      entities.Hence, high index of suspicion is required for prompt
      diagnosis.Histopathological examination and culture are the gold standard
      diagnostic tools, however no standard treatment protocols ha been mentioned in
      literature.We present a case of rhinofacial entomopthoromycosis in a yearold ma
      with a leftsided rhinofacial swelling to highlight the presence of this unusual
      fungal infection and its treatment.

PMID- 29572370
TI  - Two cases of hypokalaemic rhabdomyolysis: same but different.
AB  - In this paper, we present two women with hypokalaemic rhabdomyolysis in the
      context of increased diuretic intake and gastroenteritis, respectively. While
      their clinical manifestations and laboratory results were strikingly similar, two
      different underlying disorders were subsequently unveiled. The first patient was
      diagnosed with Conn syndrome, and adrenalectomy led to significant improvement of
      hypertension and sustained normokalaemia. The diagnosis in the second patient was
      Gitelman syndrome. Electrolyte supplements improved long-term lassitude and the
      frequency of muscle cramps declined significantly. These case vignettes
      illustrate the importance of establishing the underlying cause of hypokalaemia.

PMID- 29572371
TI  - Tarsal buckle with conjunctival prolapse following levator plication for
      unilateral congenital ptosis.
AB  - An 8-year-old child underwent uneventful levator plication surgery for unilateral
      congenital ptosis. Postoperative course for initial few days was uneventful but
      on day 7, the patient was brought with conjunctival prolapse from the
      undersurface of upper eyelid due to tarsal kinking and eversion. Early medical
      management was initiated with frequent surface lubrication to avoid conjunctiva
      dryness. Under general anaesthesia, right-sided conjunctival repositioning was
      performed with an eyelid spatula supplemented by three forniceal stay sutures to
      retain the conjunctiva in its anatomical place. To reverse the tarsal kinking,
      continued downward traction suture was placed for a period of 2 weeks. At the end
      of 4 weeks, the conjunctival prolapse was completely resolved with a well-formed
      superior fornix. At the end of 3 months, the symmetric eyelid position was
      maintained without any additional complications.

PMID- 29572372
TI  - Parkinson's disease with hypocalcaemia: adult presentation of 22q11.2 deletion
      syndrome.
AB  - A growing amount of evidence indicates that 22q11.2 deletion syndrome (22q11.2DS)
      increases the risk of early-onset Parkinson's disease (EOPD). Here, we describe a
      36-year-old patient with EOPD. The patient presented with 22q11.2DS features,
      including associated cognitive disabilities, hypocalcaemia and facial dysmorphia
      that led us to screen for and confirm this deletion. In addition, hypocalcaemia
      and vitamin D deficiency were the main factors responsible for severe, painful
      muscle spasms that were non-levodopa (L-Dopa) responsive and remitted after
      calcium and vitamin D replacement therapy. Many patients with this deletion
      remain undiagnosed until adulthood due to the absence of 'major' phenotypic
      hallmarks, which usually present during early childhood. Later onset problems
      involving various medical subspecialties are increasingly recognised as important
      components of 22q11.2DS. Therefore, the multisystem nature and associated burden
      of morbidities demand a high degree of suspicion for this entity from all
      clinicians regardless of their medical subspecialty.

PMID- 29572373
TI  - What does vanishing bone disease look like?

PMID- 29572374
TI  - Case of a fractured human bone fragment as an endobronchial foreign body
      following a traffic incident.
AB  - Endobronchial foreign bodies (EFBs) are present in various settings, such as
      eating or dental procedure. Accidental aspiration of foreign bodies is more
      common in children; however, cases of adult foreign body aspiration exist.
      Traumatic incidents can precipitate endobronchial aspiration of foreign bodies.
      Loss of consciousness, such as in coma, can result in foreign bodies being easily
      inhaled into the airways. Teeth or vehicle parts have been reported as EFBs
      following traumatic incidents. We report on a patient with chronic, sustained
      cough following maxillofacial trauma. Chest CT revealed an abnormal calcified
      endobronchial opacity. Flexible bronchoscopy confirmed the presence of an
      endobronchial foreign body in the left main bronchus. Following removal by
      bronchial forceps, the body was identified as a human bone fragment. Successful
      removal of the endobronchial bone fragment resulted in complete symptom
      remission. We concluded that post-traumatic respiratory complaints should be
      comprehensively evaluated, even if mild.

PMID- 29572375
TI  - Klippel-Trenaunay-Weber syndrome as a cause of chronic thromboembolic pulmonary
      hypertension.

PMID- 29572376
TI  - Socioeconomic status, non-communicable disease risk factors, and walking speed in
      older adults: multi-cohort population based study.
AB  - OBJECTIVE: To assess the association of low socioeconomic status and risk factors
      for non-communicable diseases (diabetes, high alcohol intake, high blood
      pressure, obesity, physical inactivity, smoking) with loss of physical
      functioning at older ages. DESIGN: Multi-cohort population based study. SETTING:
      37 cohort studies from 24 countries in Europe, the United States, Latin America,
      Africa, and Asia, 1990-2017. PARTICIPANTS: 109 107 men and women aged 45-90
      years. MAIN OUTCOME MEASURE: Physical functioning assessed using the walking
      speed test, a valid index of overall functional capacity. Years of functioning
      lost was computed as a metric to quantify the difference in walking speed between
      those exposed and unexposed to low socioeconomic status and risk factors.
      RESULTS: According to mixed model estimations, men aged 60 and of low
      socioeconomic status had the same walking speed as men aged 66.6 of high
      socioeconomic status (years of functioning lost 6.6 years, 95% confidence
      interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to
      6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years
      of functioning were lost by age 60 due to insufficient physical activity, 5.1
      (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3
      to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to
      diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In
      analyses restricted to high income countries, the number of years of functioning
      lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for
      men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it
      was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income
      countries, the number of years of functioning lost attributable to low
      socioeconomic status by age 60 was greater in the United States than in Europe.
      Physical functioning continued to decline as a function of unfavourable risk
      factors between ages 60 and 85. Years of functioning lost were greater than years
      of life lost due to low socioeconomic status and non-communicable disease risk
      factors. CONCLUSIONS: The independent association between socioeconomic status
      and physical functioning in old age is comparable in strength and consistency
      with those for established non-communicable disease risk factors. The results of
      this study suggest that tackling all these risk factors might substantially
      increase life years spent in good physical functioning.

PMID- 29572377
TI  - Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on
      toxicity and antileukemic efficacy.
AB  - Thiopurines (eg, 6-mercaptopurine [MP]) are highly efficacious antileukemic
      agents, but they are also associated with dose-limiting toxicities. Recent
      studies by us and others have identified inherited NUDT15 deficiency as a novel
      genetic cause of thiopurine toxicity, and there is a strong rationale for NUDT15
      guided dose individualization to preemptively mitigate adverse effects of these
      drugs. Using CRISPR-Cas9 genome editing, we established a Nudt15-/- mouse model
      to evaluate the effectiveness of this strategy in vivo. Across MP dosages, Nudt15
      /- mice experienced severe leukopenia, rapid weight loss, earlier death resulting
      from toxicity, and more bone marrow hypocellularity compared with wild-type mice.
      Nudt15-/- mice also showed excessive accumulation of a thiopurine active
      metabolite (ie, DNA-incorporated thioguanine nucleotides [DNA-TG]) in an MP dose
      dependent fashion, as a plausible cause of increased toxicity. MP dose reduction
      effectively normalized systemic exposure to DNA-TG in Nudt15-/- mice and largely
      eliminated Nudt15 deficiency-mediated toxicity. In 95 children with acute
      lymphoblastic leukemia, MP dose adjustment also directly led to alteration in DNA
      TG levels, the effects of which were proportional to the degree of NUDT15
      deficiency. Using leukemia-bearing mice with concordant Nudt15 genotype in
      leukemia and host, we also confirmed that therapeutic efficacy was preserved in
      Nudt15-/- mice receiving a reduced MP dose compared with Nudt15+/+ counterparts
      exposed to a standard dose. In conclusion, we demonstrated that NUDT15 genotype
      guided MP dose individualization can preemptively mitigate toxicity without
      compromising therapeutic efficacy.

PMID- 29572379
TI  - Stable lines and clones of long-term proliferating normal, genetically unmodified
      murine common lymphoid progenitors.
AB  - Common lymphoid progenitors (CLPs) differentiate to T and B lymphocytes,
      dendritic cells, natural killer cells, and innate lymphoid cells. Here, we
      describe culture conditions that, for the first time, allow the establishment of
      lymphoid-restricted, but uncommitted, long-term proliferating CLP cell lines and
      clones from a small pool of these cells from normal mouse bone marrow, without
      any genetic manipulation. Cells from more than half of the cultured CLP clones
      could be induced to differentiate to T, B, natural killer, dendritic, and myeloid
      cells in vitro. Cultured, transplanted CLPs transiently populate the host and
      differentiate to all lymphoid subsets, and to myeloid cells in vivo. This simple
      method to obtain robust numbers of cultured noncommitted CLPs will allow studies
      of cell-intrinsic and environmentally controlled lymphoid differentiation
      programs. If this method can be applied to human CLPs, it will provide new
      opportunities for cell therapy of patients in need of myeloid-lymphoid
      reconstitution.

PMID- 29572378
TI  - Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas.
AB  - Resistance to targeted therapies has become increasingly prevalent. We noted that
      resistance to different targeted therapies occurs by largely common mechanisms.
      In this study, we used this information for identifying the mechanisms of
      resistance to enhancer of zeste homolog 2 (EZH2) inhibitors in diffuse large B
      cell lymphoma (DLBCL) harboring EZH2 mutations. We discovered that EZH2 inhibitor
      resistant DLBCL cells showed activation of the insulin-like growth factor 1
      receptor (IGF-1R), MEK, and phosphoinositide-3-kinase (PI3K) pathways.
      Constitutive activation of IGF-1R, MEK, or PI3K pathways was sufficient to confer
      resistance to EZH2 inhibitors in DLBCL. The activation of the PI3K/AKT and MAPK
      pathways decreased TNFSF10 and BAD expression through a FOXO3-dependent
      mechanism, which was required for the antitumor effects of EZH2i GSK126. We also
      identified multiple acquired mutations in EZH2 inhibitor-resistant DLBCL cell
      lines. These mutations independently conferred resistance to EZH2 inhibitors.
      Mechanistically, cellular thermal shift assays revealed that the acquired EZH2
      mutations that confer resistance to EZH2 inhibitors prevent EZH2 inhibitor
      binding to the EZH2 mutants. Notably, EZH2 inhibitor GSK126- and EPZ-6438
      resistant DLBCL cells remained sensitive to the EZH2 inhibitor UNC1999 and
      embryonic ectoderm development protein inhibitor EED226, which provides an
      opportunity to treat DLBCLs that are resistant to these drugs. Collectively, our
      results underpin the importance for developing a unified approach for
      forestalling drug resistance by prospectively considering lessons learned from
      the use of different targeted therapeutic agents.

PMID- 29572380
TI  - The identification of fibrosis-driving myofibroblast precursors reveals new
      therapeutic avenues in myelofibrosis.
AB  - Myofibroblasts are fibrosis-driving cells and are well characterized in solid
      organ fibrosis, but their role and cellular origin in bone marrow fibrosis
      remains obscure. Recent work has demonstrated that Gli1+ and LepR+ mesenchymal
      stromal cells (MSCs) are progenitors of fibrosis-causing myofibroblasts in the
      bone marrow. Genetic ablation of Gli1+ MSCs or pharmacologic targeting of
      hedgehog (Hh)-Gli signaling ameliorated fibrosis in mouse models of myelofibrosis
      (MF). Moreover, pharmacologic or genetic intervention in platelet-derived growth
      factor receptor alpha (Pdgfralpha) signaling in Lepr+ stromal cells suppressed
      their expansion and ameliorated MF. Improved understanding of cellular and
      molecular mechanisms in the hematopoietic stem cell niche that govern the
      transition of MSCs to myofibroblasts and myofibroblast expansion in MF has led to
      new paradigms in the pathogenesis and treatment of MF. Here, we highlight the
      central role of malignant hematopoietic clone-derived megakaryocytes in
      reprogramming the hematopoietic stem cell niche in MF with potential detrimental
      consequences for hematopoietic reconstitution after allogenic stem cell
      transplantation, so far the only therapeutic approach in MF considered to be
      curative. We and others have reported that targeting Hh-Gli signaling is a
      therapeutic strategy in solid organ fibrosis. Data indicate that targeting Gli
      proteins directly inhibits Gli1+ cell proliferation and myofibroblast
      differentiation, which results in reduced fibrosis severity and improved organ
      function. Although canonical Hh inhibition (eg, smoothened [Smo] inhibition)
      failed to improve pulmonary fibrosis, kidney fibrosis, or MF, the direct
      inhibition of Gli proteins ameliorated fibrosis. Therefore, targeting Gli
      proteins directly might be an interesting and novel therapeutic approach in MF.

PMID- 29572381
TI  - SIRF: Quantitative in situ analysis of protein interactions at DNA replication
      forks.

PMID- 29572383
TI  - CTRP3 attenuates high-fat diet-induced male reproductive dysfunction in mice.
AB  - Recent studies have suggested a role for abdominal obesity in male infertility.
      Previous studies have found that cell apoptosis exerts an important role in
      obesity-related male infertility. C1q/TNF-related protein 3 (CTRP3), a paralog of
      adiponectin, has been proposed to exert anti-apoptotic effects and to attenuate
      diabetes-related cardiac injuries. However, the role of CTRP3 in high-fat diet
      (HFD)-induced spermatogenic impairment remains unclear. In the present study, we
      fed male mice an HFD for 24 weeks to induce obesity. The expression of CTRP3 was
      decreased by HFD feeding. Supplementation with the recombinant human globular
      domain of CTRP3 (0.25 MUg/g/day) for 4 weeks beginning at 20 weeks of the HFD
      improved spermatogenic function in the HFD-fed mice, which were characterized by
      improved testis morphology, increased testis weight/body weight ratio, and
      increased sperm count, sperm viability, and sperm motility. We also found that
      CTRP3 infusion resulted in the attenuation of endoplasmic reticulum (ER) stress
      and the activation of silence information regulator 1 (SIRT1) in the testes of
      obese mice. Our in vitro study also suggested that CTRP3 attenuated the palmitic
      acid (PA)-induced reductions in sperm viability and motility via the inhibition
      of ER stress. Moreover, germ cell-specific Sirtuin1 knockout abolished the
      protective effects of CTRP3 in vivo and in vitro. In vitro studies of human sperm
      showed that the protective effects of CTRP3 on sperm viability and motility were
      abrogated by a specific inhibitor of SIRT1. Thus, our results demonstrated that
      CTRP3 expression protected against HFD-induced spermatogenic deficiency through
      the SIRT1/ER stress pathway.

PMID- 29572382
TI  - Correlative live and super-resolution imaging reveals the dynamic structure of
      replication domains.
AB  - Chromosome organization in higher eukaryotes controls gene expression, DNA
      replication, and DNA repair. Genome mapping has revealed the functional units of
      chromatin at the submegabase scale as self-interacting regions called
      topologically associating domains (TADs) and showed they correspond to
      replication domains (RDs). A quantitative structural and dynamic description of
      RD behavior in the nucleus is, however, missing because visualization of dynamic
      subdiffraction-sized RDs remains challenging. Using fluorescence labeling of RDs
      combined with correlative live and super-resolution microscopy in situ, we
      determined biophysical parameters to characterize the internal organization,
      spacing, and mechanical coupling of RDs. We found that RDs are typically 150 nm
      in size and contain four co-replicating regions spaced 60 nm apart. Spatially
      neighboring RDs are spaced 300 nm apart and connected by highly flexible linker
      regions that couple their motion only <550 nm. Our pipeline allows a robust
      quantitative characterization of chromosome structure in situ and provides
      important biophysical parameters to understand general principles of chromatin
      organization.

PMID- 29572384
TI  - Cardiotrophin-1 attenuates experimental colitis in mice.
AB  - Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective, and anti
      apoptotic effects in the liver, kidneys, and heart. In the present study, the
      role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in
      experimental ulcerative colitis. Colitis was induced in CT-1 knockout and wild
      type (WT) mice by administration of dextran sulphate sodium (DSS) in the drinking
      water during 7 days. CT-1 knockout mice showed higher colon damage and disease
      severity than WT mice. In addition, CT-1 (200 ug/kg/day, iv) or vehicle (as
      control) was administered during 3 days to WT, colitic mice, starting on day 4
      after initiation of DSS. Disease activity index (DAI), inflammatory markers
      (tumor necrosis factor alpha (TNF-alpha), INFgamma, IL-17, IL-10, inducible
      nitric oxide synthase (iNOS)), colon damage, apoptosis (cleaved caspase 3),
      nuclear factor kappaB (NFkappaB) and STAT-3 activation, and bacterial
      translocation were measured. Compared with mice treated with DSS, mice also
      treated with exogenous CT-1 showed lower colon damage, DAI, plasma levels of
      TNFalpha, colon expression of TNF-alpha, INFgamma, IL-17, iNOS and cleaved
      caspase 3, higher NFkappaB and signal transducer and activator of transcription 3
      (STAT3) pathways activation, and absence of bacterial translocation. We conclude
      that endogenous CT-1 plays a role in the defense and repair response of the colon
      against ulcerative lesions through an anti-inflammatory and anti-apoptotic
      effect. Supplementation with exogenous CT-1 ameliorates disease symptoms, which
      opens a potentially new therapeutic strategy for ulcerative colitis.

PMID- 29572385
TI  - MiR-27-3p regulates TLR2/4-dependent mouse alveolar macrophage activation by
      targetting PPARgamma.
AB  - Activation of alveolar macrophages (AMs) and the release of cytokines play
      critical roles in the pathogenesis of chronic obstructive pulmonary disease
      (COPD). However, little is known about the mechanisms of AM activation. miRNAs
      have recently emerged as key regulators of inflammation and as mediators of
      macrophage activation and polarization. We identified potential miRNAs related to
      AM activation using miRNA microarray analysis, which showed that miR-27-3p
      expression was up-regulated in AMs and the lung tissues of mice exposed to
      cigarette smoke (CS)/lipopolysaccharide (LPS), and found that miR-27-3p regulated
      proinflammatory cytokine production and AM polarization depending on TLR2/4
      intracellular signaling in AMs. We also found that miR-27-3p controlled TLR2/4
      signaling in AMs via targetting the 3'-UTR sequences of peroxisome proliferator
      activated receptor gamma (PPARgamma) and inhibiting PPARgamma activation.
      Moreover, we found that PPARgamma activation not only inhibited CS/LPS-induced
      TLR2/4 expression and miR-27-3p-mediated TLR2/4 signaling cascades involving the
      nuclear factor-kappaB (NF-kappaB), c-Jun NH2-terminal kinase (JNK)/p38, and Janus
      kinase-signal transducer and activator of transcription (JAK/STAT) pathways in
      AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation.
      Our study revealed that miR-27-3p mediated AM activation by the inhibition of
      PPARgamma activation and sensitization of TLR signaling.

PMID- 29572386
TI  - Marauding terrorist attack (MTA): prehospital considerations.
AB  - Terrorist attacks are increasing each year as are the number of deaths associated
      with them. Recent incidents have seen a shift in tactics with the use of multiple
      terrorists across multiple locations with firearms or knives, referred to as the
      marauding terrorist attack. These methods are becoming more prevalent alongside
      the use of vehicles deliberately aimed at pedestrians. Management of these
      incidents can be challenging. Not only it involves a large number of casualties
      but also the management of a dynamic scene in terms of both location and threat
      from attack. In order to improve response, and potentially outcomes, a system or
      response needs to have preplanned and practised procedures in place. This article
      reviews major incident management for those unfamiliar with current prehospital
      practice and details some of the findings from recent marauding terrorist firearm
      attacks, in particular the evolution of newer scene management tools such as 3
      Echo and THREAT. It highlights the importance of haemorrhage control and the
      public initiatives focusing on actions during a terrorist incident.

PMID- 29572387
TI  - Automatic classification of ovarian cancer types from cytological images using
      deep convolutional neural networks.
AB  - Ovarian cancer is one of the most common gynecologic malignancies. Accurate
      classification of ovarian cancer types (serous carcinoma, mucous carcinoma,
      endometrioid carcinoma, transparent cell carcinoma) is an essential part in the
      different diagnosis. Computer-aided diagnosis (CADx) can provide useful advice
      for pathologists to determine the diagnosis correctly. In our study, we employed
      a Deep Convolutional Neural Networks (DCNN) based on AlexNet to automatically
      classify the different types of ovarian cancers from cytological images. The DCNN
      consists of five convolutional layers, three max pooling layers, and two full
      reconnect layers. Then we trained the model by two group input data separately,
      one was original image data and the other one was augmented image data including
      image enhancement and image rotation. The testing results are obtained by the
      method of 10-fold cross-validation, showing that the accuracy of classification
      models has been improved from 72.76 to 78.20% by using augmented images as
      training data. The developed scheme was useful for classifying ovarian cancers
      from cytological images.

PMID- 29572388
TI  - Unexpected role of the L-domain of calpastatin during the autoproteolytic
      activation of human erythrocyte calpain.
AB  - Autoproteolysis of human erythrocyte calpain-1 proceeds in vitro at high [Ca2+],
      through the conversion of the 80-kDa catalytic subunit into a 75-kDa activated
      enzyme that requires lower [Ca2+] for catalysis. Importantly, here we detect a
      similar 75 kDa calpain-1 form also in vivo, in human meningiomas. Although
      calpastatin is so far considered the specific inhibitor of calpains, we have
      previously identified in rat brain a calpastatin transcript truncated at the end
      of the L-domain (cast110, L-DOM), coding for a protein lacking the inhibitory
      units. Aim of the present study was to characterize the possible biochemical role
      of the L-DOM during calpain-1 autoproteolysis in vitro, at high (100 uM) and low
      (5 uM) [Ca2+]. Here we demonstrate that the L-DOM binds the 80 kDa proenzyme in
      the absence of Ca2+ Consequently, we have explored the ability of the 75 kDa
      activated protease to catalyze at 5 uM Ca2+ the intermolecular activation of
      native calpain-1 associated with the L-DOM. Notably, this [Ca2+] is too low to
      promote the autoproteolytic activation of calpain-1 but enough to support the
      catalysis of the 75 kDa calpain. We show for the first time that the L-DOM
      preserves native calpain-1 from the degradation mediated by the 75 kDa form.
      Taken together, our data suggest that the free L-domain of calpastatin is a novel
      member of the calpain/calpastatin system endowed with a function alternative to
      calpain inhibition. For this reason, it will be crucial to define the
      intracellular relevance of the L-domain in controlling calpain
      activation/activity in physiopathological conditions having altered Ca2+
      homeostasis.

PMID- 29572389
TI  - Nicotine enhances mesangial cell proliferation and fibronectin production in high
      glucose milieu via activation of Wnt/beta-catenin pathway.
AB  - Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinic
      reports indicate cigarette smoking is an independent risk factor for chronic
      kidney disease including DN; however, the underlying molecular mechanisms are not
      clear. Recent studies have demonstrated that nicotine, one of the active
      compounds in cigarette smoke, contributes to the pathogenesis of the cigarette
      smoking-accelerated chronic kidney disease. One of the characteristics of DN is
      the expansion of mesangium, a precursor of glomerular sclerosis. In the present
      study, we examined the involvement of Wnt/beta-catenin pathway in nicotine
      mediated mesangial cell growth in high glucose milieu. Primary human renal
      mesangial cells were treated with nicotine in the presence of normal (5 mM) or
      high glucose (30 mM) followed by evaluation for cell growth. In the presence of
      normal glucose, nicotine increased both the total cell numbers and Ki-67 positive
      cell ratio, indicating that nicotine stimulated mesangial cell proliferation.
      Although high glucose itself also stimulated mesangial cell proliferation,
      nicotine further enhanced the mitogenic effect of high glucose. Similarly,
      nicotine increased the expression of Wnts, beta-catenin, and fibronectin in
      normal glucose medium, but further increased mesangial cell expression of these
      proteins in high glucose milieu. Pharmacological inhibition or genetic knockdown
      of beta-catenin activity or expression with specific inhibitor FH535 or siRNA
      significantly impaired the nicotine/glucose-stimulated cell proliferation and
      fibronectin production. We conclude that nicotine may enhance renal mesangial
      cell proliferation and fibronectin production under high glucose milieus partly
      through activating Wnt/beta-catenin pathway. Our study provides insight into
      molecular mechanisms involved in DN.

PMID- 29572390
TI  - METHIONINE ADENOSYLTRANSFERASE4 Mediates DNA and Histone Methylation.
AB  - DNA and histone methylation coregulate heterochromatin formation and gene
      silencing in animals and plants. To identify factors involved in maintaining gene
      silencing, we conducted a forward genetic screen for mutants that release the
      silenced transgene Pro35S::NEOMYCIN PHOSPHOTRANSFERASE II in the transgenic
      Arabidopsis (Arabidopsis thaliana) line L119 We identified
      MAT4/SAMS3/MTO3/AT3G17390, which encodes methionine (Met) adenosyltransferase 4
      (MAT4)/S-adenosyl-Met synthetase 3 that catalyzes the synthesis of S-adenosyl-Met
      (SAM) in the one-carbon metabolism cycle. mat4 mostly decreases CHG and CHH DNA
      methylation and histone H3K9me2 and reactivates certain silenced transposons. The
      exogenous addition of SAM partially rescues the epigenetic defects of mat4 SAM
      content and DNA methylation were reduced more in mat4 than in three other mat
      mutants. MAT4 knockout mutations generated by CRISPR/Cas9 were lethal, indicating
      that MAT4 is an essential gene in Arabidopsis. MAT1, 2, and 4 proteins exhibited
      nearly equal activity in an in vitro assay, whereas MAT3 exhibited higher
      activity. The native MAT4 promoter driving MAT1, 2, and 3 cDNA complemented the
      mat4 mutant. However, most mat4 transgenic lines carrying native MAT1, 2, and 3
      promoters driving MAT4 cDNA did not complement the mat4 mutant because of their
      lower expression in seedlings. Genetic analyses indicated that the mat1mat4
      double mutant is dwarfed and the mat2mat4 double mutant was nonviable, while
      mat1mat2 showed normal growth and fertility. These results indicate that MAT4
      plays a predominant role in SAM production, plant growth, and development. Our
      findings provide direct evidence of the cooperative actions between metabolism
      and epigenetic regulation.

PMID- 29572391
TI  - Infusion of donor-derived CD8+ memory T cells for relapse following allogeneic
      hematopoietic cell transplantation.
AB  - Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate
      malignant cells without inducing graft-versus-host disease (GVHD). We evaluated
      the feasibility and safety of infusing freshly isolated and purified donor
      derived phenotypic CD8+ TM cells into adults with disease relapse after
      allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were
      isolated after unmobilized donor apheresis using a tandem immunomagnetic
      selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen
      patients received CD8+ TM cells at escalating doses (1 * 106, 5 * 106, or 10 *
      106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion,
      and 9 had active disease at the time of infusion. Mean yield and purity of the
      CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector
      memory phenotype, cytokine expression, and secretion profile. No adverse
      infusional events or dose-limiting toxicities occurred; GVHD developed in 1
      patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7
      complete response, 1 partial response, 2 stable disease) for at least 3 months
      after infusion; 4 of the responders had active disease at the time of infusion.
      With a median follow-up from infusion of 328 days (range, 118-1328 days), median
      event-free survival and overall survival were 4.9 months (95% confidence interval
      [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached),
      respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible,
      well tolerated, and associated with a low incidence of GVHD when administered as
      a manipulated infusion of donor lymphocytes in patients who have relapsed after
      HCT. This trial was registered at www.clinicaltrials.gov as #NCT01523223.

PMID- 29572392
TI  - 'And you'll suddenly realise 'I've not washed my hands': medical students',
      junior doctors' and medical educators' narratives of hygiene behaviours.
AB  - OBJECTIVE: Compliance to hygiene behaviours has long been recognised as important
      in the prevention and control of healthcare associated infections, but medical
      doctors still display some of the lowest rates of compliance of all healthcare
      workers. We aim to understand compliance to hygiene behaviours by analysing
      medical students', junior doctors' and medical educators' narratives of these
      behaviours to identify their respective attitudes and beliefs around compliance
      and how these are learnt during training. Such an understanding can inform future
      interventions to improve compliance targeted to areas of greatest need. DESIGN: A
      qualitative study, using narrative interviews (nine focus groups and one
      individual interview). Data were analysed thematically using inductive framework
      analysis. SETTING: Teaching hospitals in the UK. PARTICIPANTS: Convenience sample
      of 25 participants: third-year medical students in their first clinical year
      (n=13), junior doctors (n=6) and medical educators (n=6). RESULTS: We identified
      four main themes: (1) knowledge, (2) constraints, (3) role models/culture and (4)
      hygiene as an added extra. Knowledge varied across participant groups and
      appeared to influence behaviours; medical students relied on what they have been
      told by seniors, while medical educators relied on their own knowledge and
      experience. There was a strong belief that evidence for the effectiveness of good
      hygiene behaviours is lacking. Furthermore, medical educators' behaviour appears
      to strongly influence others. Finally, hygiene was predominately viewed as an
      added extra rather than an integral part of the process. CONCLUSIONS: Awareness
      of the evidence around good hygiene needs to be improved at all levels. Medical
      students and junior doctors should be encouraged to consider why they are asked
      to perform certain hygiene behaviours in order to improve ownership of those
      behaviours. Medical educators need to recognise their responsibilities as role
      models for their junior counterparts, thereby understanding their role in
      developing the culture of hygiene practices within their clinical domains.

PMID- 29572393
TI  - Comparative analysis of methods for identifying multimorbidity patterns: a study
      of 'real-world' data.
AB  - OBJECTIVE: The aim was to compare multimorbidity patterns identified with the two
      most commonly used methods: hierarchical cluster analysis (HCA) and exploratory
      factor analysis (EFA) in a large primary care database. Specific objectives were:
      (1) to determine whether choice of method affects the composition of these
      patterns and (2) to consider the potential application of each method in the
      clinical setting. DESIGN: Cross-sectional study. Diagnoses were based on the 263
      corresponding blocks of the International Classification of Diseases version 10.
      Multimorbidity patterns were identified using HCA and EFA. Analysis was
      stratified by sex, and results compared for each method. SETTING AND
      PARTICIPANTS: Electronic health records for 408 994 patients with multimorbidity
      aged 45-64 years in 274 primary health care teams from 2010 in Catalonia, Spain.
      RESULTS: HCA identified 53 clusters for women, with just 12 clusters including at
      least 2 diagnoses, and 15 clusters for men, all of them including at least two
      diagnoses. EFA showed 9 factors for women and 10 factors for men. We observed
      differences by sex and method of analysis, although some patterns were
      consistent. Three combinations of diseases were observed consistently across sex
      groups and across both methods: hypertension and obesity, spondylopathies and
      deforming dorsopathies, and dermatitis eczema and mycosis. CONCLUSIONS: This
      study showed that multimorbidity patterns vary depending on the method of
      analysis used (HCA vs EFA) and provided new evidence about the known limitations
      of attempts to compare multimorbidity patterns in real-world data studies. We
      found that EFA was useful in describing comorbidity relationships and HCA could
      be useful for in-depth study of multimorbidity. Our results suggest possible
      applications for each of these methods in clinical and research settings, and add
      information about some aspects that must be considered in standardisation of
      future studies: spectrum of diseases, data usage and methods of analysis.

PMID- 29572394
TI  - Effectiveness of a chronic obstructive pulmonary disease integrated care pathway
      in a regional health system: a propensity score matched cohort study.
AB  - OBJECTIVE: The chronic obstructive pulmonary disease (COPD) integrated care
      pathway (ICP) programme was designed and implemented to ensure that the care for
      patients with COPD is comprehensive and integrated across different care settings
      from primary care to acute hospital and home. We evaluated the effectiveness of
      the ICP programme for patients with COPD. DESIGN, SETTING AND PARTICIPANTS: A
      retrospective propensity score matched cohort study was conducted comparing
      differences between programme enrolees and propensity-matched non-enrolees in a
      Regional Health System in Singapore. Data on patients diagnosed with COPD who
      enrolled in the programme (n=95) and patients who did not enrol (n=6330) were
      extracted from the COPD registry and hospital administrative databases. Enrolees
      and non-enrolees were propensity score matched. OUTCOME MEASURES: The risk of
      COPD hospitalisations and COPD hospital bed days savings were compared between
      the groups using a difference-in-difference strategy and generalised estimating
      equation approach. Adherence with recommended care elements for the COPD-ICP
      group was measured quarterly at baseline and during a 2-year follow-up period.
      RESULTS: Compared with non-enrolees, COPD hospitalisation risk for ICP programme
      enrolees was significantly lower in year 2 (incidence rate ratio (IRR): 0.73; 95%
      CI 0.54 to 1.00). Similarly, COPD hospital bed days was significantly lower for
      enrolees in year 2 (IRR: 0.78; 95% CI 0.64 to 0.95). ICP programme patients had
      sustained improvements in compliance with all recommended care elements for
      patients with COPD. The overall all-or-none care bundle compliance rate had
      improved from 28% to 54%. CONCLUSION: The study concluded that the COPD-ICP
      programme was associated with reductions in COPD hospitalisation risk and COPD
      health utilisation in a 2-year follow-up period.

PMID- 29572396
TI  - Are methodological quality and completeness of reporting associated with citation
      based measures of publication impact? A secondary analysis of a systematic review
      of dementia biomarker studies.
AB  - OBJECTIVE: To determine whether methodological and reporting quality are
      associated with surrogate measures of publication impact in the field of dementia
      biomarker studies. METHODS: We assessed dementia biomarker studies included in a
      previous systematic review in terms of methodological and reporting quality using
      the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Standards for
      Reporting of Diagnostic Accuracy (STARD), respectively. We extracted additional
      study and journal-related data from each publication to account for factors shown
      to be associated with impact in previous research. We explored associations
      between potential determinants and measures of publication impact in univariable
      and stepwise multivariable linear regression analyses. OUTCOME MEASURES: We aimed
      to collect data on four measures of publication impact: two traditional measures
      average number of citations per year and 5-year impact factor of the publishing
      journal and two alternative measures-the Altmetric Attention Score and counts of
      electronic downloads. RESULTS: The systematic review included 142 studies. Due to
      limited data, Altmetric Attention Scores and electronic downloads were excluded
      from the analysis, leaving traditional metrics as the only analysed outcome
      measures. We found no relationship between QUADAS and traditional metrics.
      Citation rates were independently associated with 5-year journal impact factor
      (beta=0.42; p<0.001), journal subject area (beta=0.39; p<0.001), number of years
      since publication (beta=-0.29; p<0.001) and STARD (beta=0.13; p<0.05).
      Independent determinants of 5-year journal impact factor were citation rates
      (beta=0.45; p<0.001), statement on conflict of interest (beta=0.22; p<0.01) and
      baseline sample size (beta=0.15; p<0.05). CONCLUSIONS: Citation rates and 5-year
      journal impact factor appear to measure different dimensions of impact. Citation
      rates were weakly associated with completeness of reporting, while neither
      traditional metric was related to methodological rigour. Our results suggest that
      high publication usage and journal outlet is not a guarantee of quality and
      readers should critically appraise all papers regardless of presumed impact.

PMID- 29572395
TI  - Opportunities for better value wound care: a multiservice, cross-sectional survey
      of complex wounds and their care in a UK community population.
AB  - BACKGROUND: Complex wounds impose a substantial health economic burden worldwide.
      As wound care is managed across multiple settings by a range of healthcare
      professionals with varying levels of expertise, the actual care delivered can
      vary considerably and result in the underuse of evidence-based interventions, the
      overuse of interventions supported by limited evidence and low value healthcare.
      OBJECTIVES: To quantify the number, type and management of complex wounds being
      treated over a two-week period and to explore variations in care by comparing
      current practices in wound assessment, prevention and treatment. DESIGN: A
      multiservice cross-sectional survey. SETTING: This survey spanned eight community
      services within five Northern England NHS Trusts. RESULTS: The point prevalence
      of complex wounds in this community-based population was 16.4 per 10 000 (95% CI
      15.9 to 17.0). Based on data from 3179 patients, antimicrobial dressings were
      being used as the primary dressing for 36% of patients with complex wounds. Forty
      per cent of people with leg ulcers either had not received the recommended
      Doppler-aided Ankle Brachial Pressure Index assessment or it was unclear whether
      a recording had been taken. Thirty-one per cent of patients whose most severe
      wound was a venous leg ulcer were not receiving compression therapy, and there
      was limited use of two-layer compression hosiery. Of patients with a pressure
      ulcer, 39% were not using a pressure-relieving cushion or mattress. CONCLUSIONS:
      Marked variations were found in care, underuse of evidence-based practices and
      overuse of practices that are not supported by robust research evidence.
      Significant opportunities for delivering better value wound care therefore exist.
      Efforts should now focus on developing strategies to identify, assess and
      disinvest from products and practices supported by little or no evidence and
      enhance the uptake of those that are.

PMID- 29572397
TI  - A systematic review of interventions to support the careers of women in academic
      medicine and other disciplines.
AB  - OBJECTIVE: To summarise quantitative evaluations of interventions designed to
      support the careers of women in academia of any discipline. METHOD: A systematic
      search of English entries in PubMed, CINAHL and Google Scholar was conducted in
      September 2017. Methodological quality of the studies was independently assessed
      by two authors using the Joanna Briggs Institute quality appraisal checklists.
      Meta-analysis was not possible due to heterogeneity in methods and outcomes;
      results were synthesised and displayed narratively. RESULTS: Eighteen eligible
      studies were identified, mostly evaluating programmes in academic medicine
      departments. The most common interventions were mentoring, education,
      professional development and/or networking programmes. All programmes took a
      'bottom-up' approach in that women were responsible for opting into and devoting
      time to participation. Study quality was low overall, but all studies reported
      positive outcomes on at least one indicator. Most often this included
      improvements in self-rated skills and capabilities, or satisfaction with the
      programme offered. Results regarding tangible outcomes were mixed; while some
      studies noted improvements in promotion, retention and remuneration, others did
      not. CONCLUSIONS: This review suggests that targeted programmes have the
      potential to improve some outcomes for women in academia. However, the studies
      provide limited high-quality evidence to provide information for academic
      institutions in terms of the best way to improve outcomes for women in academia.
      The success of an intervention appears to be undermined when it relies on the
      additional labour of those it is intending to support (ie, 'bottom-up'
      approaches). As such, academic institutions should consider and evaluate the
      efficacy of 'top-down' interventions that start with change in practice of higher
      management.

PMID- 29572398
TI  - Frequency of reporting on patient and public involvement (PPI) in research
      studies published in a general medical journal: a descriptive study.
AB  - OBJECTIVES: While documented plans for patient and public involvement (PPI) in
      research are required in many grant applications, little is known about how
      frequently PPI occurs in practice. Low levels of reported PPI may mask actual
      activity due to limited PPI reporting requirements. This research analysed the
      frequency and types of reported PPI in the presence and absence of a journal
      requirement to include this information. DESIGN AND SETTING: A before and after
      comparison of PPI reported in research papers published in The BMJ before and 1
      year after the introduction of a journal policy requiring authors to report if
      and how they involved patients and the public within their papers. RESULTS:
      Between 1 June 2013 and 31 May 2014, The BMJ published 189 research papers and 1
      (0.5%) reported PPI activity. From 1 June 2015 to 31 May 2016, following the
      introduction of the policy, The BMJ published 152 research papers of which 16
      (11%) reported PPI activity. Patients contributed to grant applications in
      addition to designing studies through to coauthorship and participation in study
      dissemination. Patient contributors were often not fully acknowledged; 6 of 17
      (35%) papers acknowledged their contributions and 2 (12%) included them as
      coauthors. CONCLUSIONS: Infrequent reporting of PPI activity does not appear to
      be purely due to a failure of documentation. Reporting of PPI activity increased
      after the introduction of The BMJ's policy, but activity both before and after
      was low and reporting was inconsistent in quality. Journals, funders and research
      institutions should collaborate to move us from the current situation where PPI
      is an optional extra to one where PPI is fully embedded in practice throughout
      the research process.

PMID- 29572399
TI  - Risks of all-cause mortality and major kidney events in patients with new-onset
      primary open-angle glaucoma: a nationwide long-term cohort study in Taiwan.
AB  - OBJECTIVE: Cardiovascular risk factors are associated with primary open-angle
      glaucoma (POAG) in the general population. However, long-term mortality and major
      kidney events in patients with new-onset POAG remain unclear. METHODS: Using the
      Taiwan National Health Insurance Research Database between 1997 and 2011, 15 185
      patients with a new diagnosis of POAG were enrolled and propensity score matched
      (1:1) with 15 185 patients without ocular disorders (WODs). All-cause mortality
      and major kidney events were analysed by a multivariate Cox proportional hazards
      regression model and a competing risk regression model. RESULTS: The risk of all
      cause mortality was significantly higher in patients with new-onset POAG than in
      those WODs (adjusted HR (aHR) 2.11, 95% CI 1.76 to 2.54; p<0.001). Patients with
      POAG had higher risks of acute renal failure (ARF) (competing risk aHR 2.58, 95%
      CI 1.88 to 3.55; p<0.001) and end-stage renal disease (ESRD) (competing risk aHR
      4.84, 95% CI 3.02 to 7.77; p<0.001) than those WODs. CONCLUSIONS: Our data
      demonstrate that POAG is a risk of all-cause mortality, ARF and ESRD, thus
      needing to notice mortality and major kidney events in patients with new-onset
      POAG.

PMID- 29572401
TI  - Correction: An electronic health records cohort study on heart failure following
      myocardial infarction in England: incidence and predictors.

PMID- 29572402
TI  - Correction: Prevalence of coronary artery calcification in a non-specific chest
      pain population in emergency and cardiology departments compared with the
      background population: a prospective cohort study in Southern Denmark with 12
      month follow-up of cardiac endpoints.

PMID- 29572400
TI  - Improving the management of pain from advanced cancer in the community: study
      protocol for a pragmatic multicentre randomised controlled trial.
AB  - INTRODUCTION: For patients with advanced cancer, research shows that pain is
      frequent, burdensome and undertreated. Evidence-based approaches to support
      cancer pain management have been developed but have not been implemented within
      the context of the UK National Health Service. This protocol is for a pragmatic
      multicentre randomised controlled trial (RCT) to assess feasibility,
      acceptability, effectiveness and cost-effectiveness for a multicomponent
      intervention for pain management in patients with advanced cancer. METHODS AND
      ANALYSIS: This trial will assess the feasibility of implementation and uptake of
      evidence-based interventions, developed and piloted as part of the Improving the
      Management of Pain from Advanced Cancer in the Community Programme grant, into
      routine clinical practice and determine whether there are potential differences
      with respect to patient-rated pain, patient pain knowledge and experience,
      healthcare use, quality of life and cost-effectiveness. 160 patients will receive
      either the intervention (usual care plus supported self-management) delivered
      within the oncology clinic and palliative care services by locally assigned
      community palliative care nurses, consisting of a self-management educational
      intervention and eHealth intervention for routine pain assessment and monitoring;
      or usual care. The primary outcomes are to assess implementation and uptake of
      the interventions, and differences in terms of pain severity. Secondary outcomes
      include pain interference, participant pain knowledge and experience, and cost
      effectiveness. Outcome assessment will be blinded and patient-reported outcome
      measures collected via post at 6 and 12 weeks following randomisation. ETHICS AND
      DISSEMINATION: This RCT has the potential to significantly influence National
      Health Service delivery to community-based patients with pain from advanced
      cancer. We aim to provide definitive evidence of whether two simple interventions
      delivered by community palliative care nurse in palliative care that support-self
      management are clinically effective and cost-effective additions to standard
      community palliative care. TRIAL REGISTRATION NUMBER: ISRCTN18281271; Pre
      results.

PMID- 29572403
TI  - Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPbeta
      in Vasopressin-Sensitive Collecting Duct Cells.
AB  - Background Renal water excretion is controlled by vasopressin, in part through
      regulation of the transcription of the aquaporin-2 gene (Aqp2).Methods To
      identify enhancer regions likely to be involved in the regulation of Aqp2 and
      other principal cell-specific genes, we used several next generation DNA
      sequencing techniques in a well characterized cultured cell model of collecting
      duct principal cells (mpkCCD). To locate enhancers, we performed the assay for
      transposase-accessible chromatin using sequencing (ATAC-Seq) to identify
      accessible regions of DNA and integrated the data with data generated by
      chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP
      Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation,
      and RNA polymerase II.Results We identified two high-probability enhancers
      centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start
      site. Motif analysis of these regions and the Aqp2 promoter identified several
      potential transcription factor binding sites, including sites for two b-ZIP
      transcription factors: CCAAT/enhancer binding protein-beta (C/EBPbeta) and cAMP
      responsive element binding protein (CREB). To identify genomic binding sites for
      both, we conducted ChIP-Seq using well characterized antibodies. In the presence
      of vasopressin, C/EBPbeta, a pioneer transcription factor critical to cell
      specific gene expression, bound strongly at the identified enhancer downstream
      from Aqp2 However, over multiple replicates, we found no detectable CREB binding
      sites within 390 kb of Aqp2 Thus, any role for CREB in the regulation of Aqp2
      gene transcription is likely to be indirect.Conclusions The analysis identified
      two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and
      showed C/EBPbeta (but not CREB) binding.

PMID- 29572404
TI  - Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct
      Models.
AB  - Background FSGS is a pattern of podocyte injury that leads to loss of glomerular
      function. Podocytes support other podocytes and glomerular capillary structure,
      oppose hemodynamic forces, form the slit diaphragm, and have mechanical
      properties that permit these functions. However, the biophysical characteristics
      of glomeruli and podocytes in disease remain unclear.Methods Using
      microindentation, atomic force microscopy, immunofluorescence microscopy,
      quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we
      studied the biophysical and structural properties of glomeruli and podocytes in
      chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration
      [cytoskeletal rearrangement]) models of podocyte injury.Results Compared with
      wild-type glomeruli, Tg26 glomeruli became progressively more deformable with
      disease progression, despite increased collagen content. Tg26 podocytes had
      disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion;
      they failed to respond to mechanical signals and exerted minimal traction force
      in three-dimensional collagen gels. Protamine treatment had similar but milder
      effects on glomeruli and podocytes.Conclusions Reduced structural integrity of
      Tg26 podocytes causes increased deformability of glomerular capillaries and
      limits the ability of capillaries to counter hemodynamic force, possibly leading
      to further podocyte injury. Loss of normal podocyte mechanical integrity could
      injure neighboring podocytes due to the absence of normal biophysical signals
      required for podocyte maintenance. The severe defects in podocyte mechanical
      behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively,
      despite increased collagen deposition, and may be the basis for the rapid course
      of glomerular diseases associated with severe podocyte injury. In milder injury
      (protamine), similar processes occur but over a longer time.

PMID- 29572406
TI  - Is routine measurement of TSH in hospitalized patients necessary?
AB  - TSH routine testing in hospitalized patients has low efficacy, but may be
      beneficial in a selected subgroup of patients. Our aim was to evaluate the
      efficacy of routine thyroid function tests among patients admitted to internal
      medicine departments. It is a retrospective study. A randomly selected cohort of
      hospitalized patients with abnormal thyroid-stimulating hormone (TSH) blood tests
      drawn as part of admission protocol. Patient data were collected from the
      electronic medical files and analyzed for its efficacy. TSH as a screening test
      was proven unnecessary in 75% (174) of the study population. Leading causes were
      non-thyroidal illness syndrome, drugs affecting the test results and subclinical
      disorders. TSH testing was found to be clinically helpful in only 9 patients;
      however, all of them had other clinical need for TSH testing. We found a
      clinically abnormal TSH in 20 patients, hypothyroidism in 11 patients and
      thyrotoxicosis in 9 patients. Low efficacy ascribed to TSH screening test by this
      study correlates with recent recommendations that indicate TSH screening in
      admitted patients only with accompanying clinical suspicion. Most probably, the
      majority of patients found by screening to have thyrotoxicosis have non-thyroidal
      illness or drug effects so the threshold for FT4 to diagnose overt thyrotoxicosis
      should be higher than that in ambulatory patients. In elderly patients,
      clinically relevant TSH disturbances are more frequent and are harder to
      diagnose, therefore, TSH screening in this group of patients might be beneficial.

PMID- 29572407
TI  - Brexit and biosecurity.

PMID- 29572409
TI  - 'Extremely concerning' deaths at Cheltenham.

PMID- 29572408
TI  - Schedule 3 'grey areas' must be cleared up.

PMID- 29572412
TI  - Gone to the dogs: greyhound figures spark new criticism.
AB  - As the Greyhound Board of Great Britain releases new figures on injuries and
      retirement, Matthew Limb explores the reaction of those who work in the industry.

PMID- 29572415
TI  - Psoroptic mange in cattle in Scotland.

PMID- 29572416
TI  - Gaining insights into the health of non-caged layer hens.

PMID- 29572418
TI  - A. C. Palmer Award.

PMID- 29572419
TI  - Badger culling and the impact on hedgehogs.

PMID- 29572420
TI  - Radiography use in small animal practice.

PMID- 29572421
TI  - Radiography use in small animal practice.

PMID- 29572422
TI  - Squirrelpox virus antibodies detected in red squirrels.

PMID- 29572405
TI  - Thyroid-disrupting chemicals and brain development: an update.
AB  - This review covers recent findings on the main categories of thyroid hormone
      disrupting chemicals and their effects on brain development. We draw mostly on
      epidemiological and experimental data published in the last decade. For each
      chemical class considered, we deal with not only the thyroid hormone-disrupting
      effects but also briefly mention the main mechanisms by which the same chemicals
      could modify estrogen and/or androgen signalling, thereby exacerbating adverse
      effects on endocrine-dependent developmental programmes. Further, we emphasize
      recent data showing how maternal thyroid hormone signalling during early
      pregnancy affects not only offspring IQ, but also neurodevelopmental disease
      risk. These recent findings add to established knowledge on the crucial
      importance of iodine and thyroid hormone for optimal brain development. We
      propose that prenatal exposure to mixtures of thyroid hormone-disrupting
      chemicals provides a plausible biological mechanism contributing to current
      increases in the incidence of neurodevelopmental disease and IQ loss.

PMID- 29572423
TI  - Recruitment challenges in the profession ... a chance to respond.
AB  - In last week's Vet Record, we published an interview with Simon Innes, chief
      executive of CVS, in which he discussed vet salaries, recruitment challenges and
      his ambitions for the future. He criticised the RCVS and organisations that
      represent vets and vet nurses for not doing enough to tackle the recruitment
      crisis. Here, we give the RCVS and BVA the opportunity to respond to these
      criticisms.

PMID- 29572424
TI  - Philip Taylor Williamson.
AB  - A practitioner who involved himself in local and national veterinary associations
      and also served in the army, as a government vet, a media vet, as well as
      teaching veterinary nurses.

PMID- 29572427
TI  - Intrinsic curvature in wool fibres is determined by the relative length of
      orthocortical and paracortical cells.
AB  - Hair curvature underpins structural diversity and function in mammalian coats,
      but what causes curl in keratin hair fibres? To obtain structural data to
      determine one aspect of this question, we used confocal microscopy to provide in
      situ measurements of the two cell types that make up the cortex of merino wool
      fibres, which was chosen as a well-characterised model system representative of
      narrow diameter hairs, such as underhairs. We measured orthocortical and
      paracortical cross-sectional areas, and cortical cell lengths, within individual
      fibre snippets of defined uniplanar curvature. This allowed a direct test of two
      long-standing theories of the mechanism of curvature in hairs. We found evidence
      contradicting the theory that curvature results from there being more cells on
      the side of the fibre closest to the outside, or convex edge, of curvature. In
      all cases, the orthocortical cells close to the outside of curvature were longer
      than paracortical cells close to the inside of the curvature, which supports the
      theory that curvature is underpinned by differences in cell type length. However,
      the latter theory also implies that, for all fibres, curvature should correlate
      with the proportions of orthocortical and paracortical cells, and we found no
      evidence for this. In merino wool, it appears that the absolute length of cells
      of each type and proportion of cells varies from fibre to fibre, and only the
      difference between the length of the two cell types is important. Implications
      for curvature in higher diameter hairs, such as guard hairs and those on the
      human scalp, are discussed.

PMID- 29572428
TI  - Structure of a monolayer of molecular rotors on aqueous subphase from grazing
      incidence X-ray diffraction.
AB  - In situ grazing-incidence X-ray scattering shows that a monolayer of artificial
      rod-shaped dipolar molecular rotors produced on the surface of an aqueous
      subphase in a Langmuir trough has a structure conducive to a 2D ferroelectric
      phase. The axes of the rotors stand an average of 0.83 nm apart in a triangular
      grid, perpendicular to the surface within experimental error. They carry 2,3
      dichlorophenylene rotators near rod centers, between two decks of interlocked
      triptycenes installed axially on the rotor axle. The analysis is based first on
      simultaneous fitting of observed Bragg rods and second on fitting the
      reflectivity curve with only three adjustable parameters and the calculated rotor
      electron density, which also revealed the presence of about seven molecules of
      water near each rotator. Dependent on preparation conditions, a minor and
      variable amount of a different crystal phase may also be present in the
      monolayer.

PMID- 29572429
TI  - Catalyst design by scanning probe block copolymer lithography.
AB  - Scanning probe block copolymer lithography (SPBCL), in combination with density
      functional theory (DFT), has been used to design and synthesize hydrogen
      evolution catalysts. DFT was used to calculate the hydrogen adsorption energy on
      a series of single-element, bimetallic, and trimetallic (Au, Pt, Ni, and Cu)
      substrates to provide leads that could be synthesized in the form of alloy or
      phase-separated particles via SPBCL. PtAuCu (18 nm, ~1:1:1 stoichiometry) has
      been identified as a homogeneous alloy phase that behaves as an effective
      hydrogen evolution catalyst in acidic aqueous media, even when it is made in bulk
      form via solution phase methods. Significantly, the bulk-prepared PtAuCu/C
      nanocatalyst discovered via this process exhibits an activity seven times higher
      than that of the state-of-the-art commercial Pt/C catalyst (based upon Pt
      content). The advantage of using SPBCL in the discovery process is that one can
      uniformly make particles, each consisting of a uniform phase combination (e.g.,
      all alloy or all phase-segregated species) at a fixed elemental ratio, an
      important consideration when working with polyelemental species where multiple
      phases may exist.

PMID- 29572432
TI  - Cell-Type-Specific Shank2 Deletion in Mice Leads to Differential Synaptic and
      Behavioral Phenotypes.
AB  - Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic
      regulation and psychiatric disorders including autism spectrum disorders.
      Conventional Shank2-mutant (Shank2-/-) mice display several autistic-like
      behaviors, including social deficits, repetitive behaviors, hyperactivity, and
      anxiety-like behaviors. However, cell-type-specific contributions to these
      behaviors have remained largely unclear. Here, we deleted Shank2 in specific cell
      types and found that male mice lacking Shank2 in excitatory neurons (CaMKII
      Cre;Shank2fl/fl) show social interaction deficits and mild social communication
      deficits, hyperactivity, and anxiety-like behaviors. In particular, male mice
      lacking Shank2 in GABAergic inhibitory neurons (Viaat-Cre;Shank2fl/fl) display
      social communication deficits, repetitive self-grooming, and mild hyperactivity.
      These behavioral changes were associated with distinct changes in hippocampal and
      striatal synaptic transmission in the two mouse lines. These results indicate
      that cell-type-specific deletions of Shank2 in mice lead to differential synaptic
      and behavioral abnormalities.SIGNIFICANCE STATEMENT Shank2 is an abundant
      excitatory postsynaptic scaffolding protein implicated in the regulation of
      excitatory synapses and diverse psychiatric disorders including autism spectrum
      disorders. Previous studies have reported in vivo functions of Shank2 mainly
      using global Shank2-null mice, but it remains largely unclear how individual cell
      types contribute to Shank2-dependent regulation of neuronal synapses and
      behaviors. Here, we have characterized conditional Shank2-mutant mice carrying
      the Shank2 deletion in excitatory and inhibitory neurons. These mouse lines
      display distinct alterations of synaptic transmission in the hippocampus and
      striatum that are associated with differential behavioral abnormalities in
      social, repetitive, locomotor, and anxiety-like domains.

PMID- 29572431
TI  - A Gain-of-Function Mutation in the alpha9 Nicotinic Acetylcholine Receptor Alters
      Medial Olivocochlear Efferent Short-Term Synaptic Plasticity.
AB  - Gain control of the auditory system operates at multiple levels. Cholinergic
      medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic
      contacts at the base of the outer hair cells (OHCs), the final targets of several
      feedback loops from the periphery and higher-processing centers. Efferent
      activation inhibits OHC active amplification within the mammalian cochlea,
      through the activation of a calcium-permeable alpha9alpha10 ionotropic
      cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated
      SK2 potassium channels. Correct operation of this feedback requires careful
      matching of acoustic input with the strength of cochlear inhibition (Galambos,
      1956; Wiederhold and Kiang, 1970; Gifford and Guinan, 1987), which is driven by
      the rate of MOC activity and short-term facilitation at the MOC-OHC synapse
      (Ballestero et al., 2011; Katz and Elgoyhen, 2014). The present work shows (in
      mice of either sex) that a mutation in the alpha9alpha10 nAChR with increased
      duration of channel gating (Taranda et al., 2009) greatly elongates hair cell
      evoked IPSCs and Ca2+ signals. Interestingly, MOC-OHC synapses of L9'T mice
      presented reduced quantum content and increased presynaptic facilitation. These
      phenotypic changes lead to enhanced and sustained synaptic responses and OHC
      hyperpolarization upon high-frequency stimulation of MOC terminals. At the
      cochlear physiology level these changes were matched by a longer time course of
      efferent MOC suppression. This indicates that the properties of the MOC-OHC
      synapse directly determine the efficacy of the MOC feedback to the cochlea being
      a main player in the "gain control" of the auditory periphery.SIGNIFICANCE
      STATEMENT Plasticity can involve reciprocal signaling across chemical synapses.
      An opportunity to study this phenomenon occurs in the mammalian cochlea whose
      sensitivity is regulated by efferent olivocochlear neurons. These release
      acetylcholine to inhibit sensory hair cells. A point mutation in the hair cell's
      acetylcholine receptor that leads to increased gating of the receptor greatly
      elongates IPSCs. Interestingly, efferent terminals from mutant mice present a
      reduced resting release probability. However, upon high-frequency stimulation
      transmitter release facilitates strongly to produce stronger and far longer
      lasting inhibition of cochlear function. Thus, central neuronal feedback on
      cochlear hair cells provides an opportunity to define plasticity mechanisms in
      cholinergic synapses other than the highly studied neuromuscular junction.

PMID- 29572430
TI  - Rlip depletion prevents spontaneous neoplasia in TP53 null mice.
AB  - TP53 (p53) is a tumor suppressor whose functions are lost or altered in most
      malignancies. p53 homozygous knockout (p53-/-) mice uniformly die of spontaneous
      malignancy, typically T-cell lymphoma. RALBP1 (RLIP76, Rlip) is a stress
      protective, mercapturic acid pathway transporter protein that also functions as a
      Ral effector involved in clathrin-dependent endocytosis. In stark contrast to p53
      /- mice, Rlip-/- mice are highly resistant to carcinogenesis. We report here that
      partial Rlip deficiency induced by weekly administration of an Rlip-specific
      phosphorothioate antisense oligonucleotide, R508, strongly inhibited spontaneous
      as well as benzo(a)pyrene-induced carcinogenesis in p53-/- mice. This treatment
      effectively prevented large-scale methylomic and transcriptomic abnormalities
      suggestive of inflammation found in cancer-bearing p53-/- mice. The remarkable
      efficiency with which Rlip deficiency suppresses spontaneous malignancy in p53-/-
      mice has not been observed with any previously reported pharmacologic or genetic
      intervention. These findings are supported by cross-breeding experiments
      demonstrating that hemizygous Rlip deficiency also reduces the spontaneous
      malignancy phenotype of p53+/- mice. Rlip is found on the cell surface, and
      antibodies directed against Rlip were found to inhibit growth and promote
      apoptosis of cell lines as effectively as Rlip siRNA. The work presented here
      investigates several features, including oxidative DNA damage of the Rlip-p53
      association in malignant transformation, and offers a paradigm for the mechanisms
      of tumor suppression by p53 and the prospects of suppressing spontaneous
      malignancy in hereditary cancer syndromes such as Li-Fraumeni.

PMID- 29572433
TI  - Cholinergic Modulation of Frontoparietal Cortical Network Dynamics Supporting
      Supramodal Attention.
AB  - A critical function of attention is to support a state of readiness to enhance
      stimulus detection, independent of stimulus modality. The nucleus basalis
      magnocellularis (NBM) is the major source of the neurochemical acetylcholine
      (ACh) for frontoparietal cortical networks thought to support attention. We
      examined a potential supramodal role of ACh in a frontoparietal cortical
      attentional network supporting target detection. We recorded local field
      potentials (LFPs) in the prelimbic frontal cortex (PFC) and the posterior
      parietal cortex (PPC) to assess whether ACh contributed to a state of readiness
      to alert rats to an impending presentation of visual or olfactory targets in one
      of five locations. Twenty male Long-Evans rats underwent training and then
      lesions of the NBM using the selective cholinergic immunotoxin 192 IgG-saporin
      (0.3 MUg/MUl; ACh-NBM-lesion) to reduce cholinergic afferentation of the cortical
      mantle. Postsurgery, ACh-NBM-lesioned rats had less correct responses and more
      omissions than sham-lesioned rats, which changed parametrically as we increased
      the attentional demands of the task with decreased target duration. This
      parametric deficit was found equally for both sensory targets. Accurate detection
      of visual and olfactory targets was associated specifically with increased LFP
      coherence, in the beta range, between the PFC and PPC, and with increased beta
      power in the PPC before the target's appearance in sham-lesioned rats. Readiness
      associated changes in brain activity and visual and olfactory target detection
      were attenuated in the ACh-NBM-lesioned group. Accordingly, ACh may support
      supramodal attention via modulating activity in a frontoparietal cortical
      network, orchestrating a state of readiness to enhance target
      detection.SIGNIFICANCE STATEMENT We examined whether the neurochemical
      acetylcholine (ACh) contributes to a state of readiness for target detection, by
      engaging frontoparietal cortical attentional networks independent of modality. We
      show that ACh supported alerting attention to an impending presentation of either
      visual or olfactory targets. Using local field potentials, enhanced stimulus
      detection was associated with an anticipatory increase in power in the beta
      oscillation range before the target's appearance within the posterior parietal
      cortex (PPC) as well as increased synchrony, also in beta, between the prefrontal
      cortex and PPC. These readiness-associated changes in brain activity and behavior
      were attenuated in rats with reduced cortical ACh. Thus, ACh may act, in a
      supramodal manner, to prepare frontoparietal cortical attentional networks for
      target detection.

PMID- 29572434
TI  - Convergence and Divergence of CRH Amacrine Cells in Mouse Retinal Circuitry.
AB  - Inhibitory interneurons sculpt the outputs of excitatory circuits to expand the
      dynamic range of information processing. In mammalian retina, >30 types of
      amacrine cells provide lateral inhibition to vertical, excitatory bipolar cell
      circuits, but functional roles for only a few amacrine cells are well
      established. Here, we elucidate the function of corticotropin-releasing hormone
      (CRH)-expressing amacrine cells labeled in Cre-transgenic mice of either sex. CRH
      cells costratify with the ON alpha ganglion cell, a neuron highly sensitive to
      positive contrast. Electrophysiological and optogenetic analyses demonstrate that
      two CRH types (CRH-1 and CRH-3) make GABAergic synapses with ON alpha cells. CRH
      1 cells signal via graded membrane potential changes, whereas CRH-3 cells fire
      action potentials. Both types show sustained ON-type responses to positive
      contrast over a range of stimulus conditions. Optogenetic control of transmission
      at CRH-1 synapses demonstrates that these synapses are tuned to low temporal
      frequencies, maintaining GABA release during fast hyperpolarizations during brief
      periods of negative contrast. CRH amacrine cell output is suppressed by prolonged
      negative contrast, when ON alpha ganglion cells continue to receive inhibitory
      input from converging OFF-pathway amacrine cells; the converging ON- and OFF
      pathway inhibition balances tonic excitatory drive to ON alpha cells. Previously,
      it was demonstrated that CRH-1 cells inhibit firing by suppressed-by-contrast
      (SbC) ganglion cells during positive contrast. Therefore, divergent outputs of
      CRH-1 cells inhibit two ganglion cell types with opposite responses to positive
      contrast. The opposing responses of ON alpha and SbC ganglion cells are explained
      by differing excitation/inhibition balance in the two circuits.SIGNIFICANCE
      STATEMENT A goal of neuroscience research is to explain the function of neural
      circuits at the level of specific cell types. Here, we studied the function of
      specific types of inhibitory interneurons, corticotropin-releasing hormone (CRH)
      amacrine cells, in the mouse retina. Genetic tools were used to identify and
      manipulate CRH cells, which make GABAergic synapses with a well studied ganglion
      cell type, the ON alpha cell. CRH cells converge with other types of amacrine
      cells to tonically inhibit ON alpha cells and balance their high level of
      excitation. CRH cells diverge to different types of ganglion cell, the unique
      properties of which depend on their balance of excitation and inhibition.

PMID- 29572435
TI  - beta-Arrestin 1/2 Aggravates Podocyte Apoptosis of Diabetic Nephropathy via
      Wnt/beta-Catenin Pathway.
AB  - BACKGROUND beta-arrestins have been shown to play a critical role in the
      progression of diabetic nephropathy. Nevertheless, the potential mechanism of
      beta-arrestins on the regulation of podocyte apoptosis has rarely been discussed.
      This study aimed to elucidate the regulation of beta-arrestin 1/2 on podocyte
      apoptosis through the Wnt/b-catenin pathway. MATERIAL AND METHODS This study
      structured beta-arrestin 1/2 down-regulated and up-regulated expression by
      plasmid transfection. The protein levels were detected with Western blotting, and
      mRNA expression was detected with RT-qPCR. The apoptotic cells were measured by
      flow cytometry. RESULTS beta-arrestin 1/2 expression levels of podocytes were up
      regulated in high-glucose-induced podocytes. beta-arrestin 1/2 overexpression
      inhibited the expression of nephrin and podocin protein. Up-regulated beta
      arrestin 1/2 promoted podocyte apoptosis and p53 pathway by increasing Bax,
      cleaved caspase-3, and p-p53 levels in high-glucose-induced podocytes. Flow
      cytometry showed that the apoptotic cells were markedly higher in the b-arrestin
      1/2 up-regulated group compared with the scramble group. Expression of beta
      catenin was increased in the beta-arrestin 1/2 up-regulated group, which
      indicated that the Wnt/b-catenin pathway was activated. Wnt/b-catenin pathway
      inhibitor (Dkk1) distinctly suppressed the apoptosis induced by beta-arrestin 1/2
      overexpression and high glucose. CONCLUSIONS These results provide a molecular
      pathomechanism of beta-arrestin 1/2 and Wnt/beta-catenin pathway on podocyte
      apoptosis and provide new ideas for the treatment of diabetic nephropathy, which
      paves the way for the future study of diabetic nephropathy and podocytes.

PMID- 29572437
TI  - Correspondence: Reply to 'Challenging a proposed role for TRPC5 in aortic
      baroreceptor pressure-sensing'.

PMID- 29572436
TI  - Pulmonary Artery Rupture Management with a Single Lumen Endotracheal Tube: Old
      Tricks that Should be Revisited.
AB  - BACKGROUND Pulmonary artery rupture can be a lethal complication of a pulmonary
      artery catheter (PAC). Different techniques have been used to manage PAC-induced
      pulmonary artery rupture, including double lumen endotracheal tube (DLT),
      bronchial blockers, pulmonary artery embolization, thoracotomy with hematoma
      evacuation, and extracorporeal life support for ventilation (ECLS). Single lumen
      endotracheal tube (ETT) is not frequently reported in the literature despite its
      advantages. CASE REPORT The authors present a case of PAC-induced pulmonary
      artery rupture successfully managed with a single lumen ETT. Although single
      lumen ETT is more labor intensive and requires constant critical care attention,
      the advantages of this technique are reported in this case in comparison to other
      well-documented therapies. CONCLUSIONS With on-going pulmonary bleeding, a single
      lumen ETT intubation offers advantages to the commonly advocated methods of
      treating a PAC-induced pulmonary artery rupture.

PMID- 29572438
TI  - Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport
      unravels direct antitumor and radiosensitizing effects.
AB  - Lactate exchange between glycolytic and oxidative cancer cells is proposed to
      optimize tumor growth. Blocking lactate uptake through monocarboxylate
      transporter 1 (MCT1) represents an attractive therapeutic strategy but may
      stimulate glucose consumption by oxidative cancer cells. We report here that
      inhibition of mitochondrial pyruvate carrier (MPC) activity fulfils the tasks of
      blocking lactate use while preventing glucose oxidative metabolism. Using in
      vitro 13C-glucose and in vivo hyperpolarized 13C-pyruvate, we identify 7ACC2 as a
      potent inhibitor of mitochondrial pyruvate transport which consecutively blocks
      extracellular lactate uptake by promoting intracellular pyruvate accumulation.
      Also, while in spheroids MCT1 inhibition leads to cytostatic effects, MPC
      activity inhibition induces cytotoxic effects together with glycolysis
      stimulation and uncompensated inhibition of mitochondrial respiration. Hypoxia
      reduction obtained with 7ACC2 is further shown to sensitize tumor xenografts to
      radiotherapy. This study positions MPC as a control point for lactate metabolism
      and expands on the anticancer potential of MPC inhibition.

PMID- 29572439
TI  - Author Correction: Myoblasts and macrophages are required for therapeutic
      morpholino antisense oligonucleotide delivery to dystrophic muscle.
AB  - The originally published version of this Article contained an error in Figure 6.
      In panel b, the top graph (BrdU 21-24d) and the bottom graph (BrdU 28-31d) were
      inadvertently swapped. This error has now been corrected in both the PDF and HTML
      versions of the Article.

PMID- 29572440
TI  - A biochemical network controlling basal myosin oscillation.
AB  - The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells,
      oscillates spontaneously in a wide variety of systems. Although much of the
      signal cascade regulating myosin activity has been characterized, the origin of
      such oscillatory behavior is still unclear. Here, we show that basal myosin II
      oscillation in Drosophila ovarian epithelium is not controlled by actomyosin
      cortical tension, but instead relies on a biochemical oscillator involving ROCK
      and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking
      junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self
      activation loop reliant on ROCK kinase activity. In response to the resulting
      myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK
      and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and
      optogenetics, we uncover an intrinsic biochemical oscillator at the core of
      myosin II regulatory network, shedding light on the spatio-temporal dynamics of
      force generation.

PMID- 29572441
TI  - A tiny Triassic saurian from Connecticut and the early evolution of the diapsid
      feeding apparatus.
AB  - Following the Permo-Triassic Extinction, large-bodied diapsid reptiles-with a
      body length >1 m-rapidly expanded their ecological roles. This diversification is
      reflected in enormous disparity in the development of the rostrum and adductor
      chamber. However, it is unclear how marked the diversity of the feeding apparatus
      was in contemporary small-bodied diapsids. Here we describe the remarkably small
      skull (2.5 cm long) of a saurian reptile, Colobops noviportensis, gen. et sp.
      nov., from the Triassic New Haven Arkose of Connecticut, USA. The taxon possesses
      an exceptionally reinforced snout and strikingly expanded supratemporal fossae
      for adductor musculature relative to any known Mesozoic or Recent diapsid of
      similar size. Our phylogenetic analyses support C. noviportensis as an early
      diverging pan-archosaur. Colobops noviportensis reveals extraordinary disparity
      of the feeding apparatus in small-bodied early Mesozoic diapsids, and a suite of
      morphologies, functionally related to a powerful bite, unknown in any small
      bodied diapsid.

PMID- 29572442
TI  - A loop region of BAFF controls B cell survival and regulates recognition by
      different inhibitors.
AB  - The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune
      diseases and is targeted in the clinic for the treatment of systemic lupus
      erythematosus. BAFF contains a loop region designated the flap, which is
      dispensable for receptor binding. Here we show that the flap of BAFF has two
      functions. In addition to facilitating the formation of a highly active BAFF 60
      mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR)
      into a signaling event via oligomerization of individual BAFF-BAFFR complexes.
      Binding and activation of BAFFR can therefore be targeted independently to
      inhibit or activate the function of BAFF. Moreover, structural analyses suggest
      that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF
      antibody (belimumab) but not of a decoy receptor (atacicept). The observed
      differences in profiles of BAFF inhibition may confer distinct biological and
      clinical efficacies to these therapeutically relevant inhibitors.

PMID- 29572443
TI  - A neuronal basis for fear discrimination in the lateral amygdala.
AB  - In the presence of new stimuli, it is crucial for survival to react with
      defensive responses in the presence of stimuli that resemble threats but also to
      not react with defensive behavior in response to new harmless stimuli. Here, we
      show that in the presence of new uncertain stimuli with sensory features that
      produce an ambiguous interpretation, discriminative processes engage a subset of
      excitatory and inhibitory neurons within the lateral amygdala (LA) that are
      partially different from those engaged by fear processes. Inducing the
      pharmacogenetic deletion of this neuronal ensemble caused fear generalization but
      left anxiety-like response, fear memory and extinction processes intact. These
      data reveal that two opposite neuronal processes account for fear discrimination
      and generalization within the LA and suggest a potential pathophysiological
      mechanism for the impaired discrimination that characterizes fear-related
      disorders.

PMID- 29572444
TI  - Designed heterogeneous palladium catalysts for reversible light-controlled
      bioorthogonal catalysis in living cells.
AB  - As a powerful tool for chemical biology, bioorthogonal chemistry broadens the
      ways to explore the mystery of life. In this field, transition metal catalysts
      (TMCs) have received much attention because TMCs can rapidly catalyze chemical
      transformations that cannot be accomplished by bio-enzymes. However, fine
      controlling chemical reactions in living systems like bio-enzymes is still a
      great challenge. Herein, we construct a versatile light-controlled bioorthogonal
      catalyst by modifying macroporous silica-Pd0 with supramolecular complex of
      azobenzene (Azo) and beta-cyclodextrin (CD). Its catalytic activity can be
      regulated by light-induced structural changes, mimicking allosteric regulation
      mechanism of bio-enzymes. The light-gated heterogeneous TMCs are important for in
      situ controlling bioorthogonal reactions and have been successfully used to
      synthesize a fluorescent probe for cell imaging and mitochondria-specific
      targeting agent by Suzuki-Miyaura cross-coupling reaction. Endowing the
      bioorthogonal catalyst with new functions is highly valuable for realizing more
      complex researches in biochemistry.

PMID- 29572445
TI  - Diatom frustules protect DNA from ultraviolet light.
AB  - The evolutionary causes for generation of nano and microstructured silica by
      photosynthetic algae are not yet deciphered. Diatoms are single photosynthetic
      algal cells populating the oceans and waters around the globe. They generate a
      considerable fraction (20-30%) of all oxygen from photosynthesis, and 45% of
      total primary production of organic material in the sea. There are more than
      100,000 species of diatoms, classified by the shape of the glass cage in which
      they live, and which they build during algal growth. These glass structures have
      accumulated for the last 100 million of years, and left rich deposits of
      nano/microstructured silicon oxide in the form of diatomaceous earth around the
      globe. Here we show that reflection of ultraviolet light by nanostructured silica
      can protect the deoxyribonucleic acid (DNA) in the algal cells, and that this may
      be an evolutionary cause for the formation of glass cages.

PMID- 29572446
TI  - Transcriptome Profiles Reveal the Crucial Roles of Hormone and Sugar in the Bud
      Dormancy of Prunus mume.
AB  - Bud dormancy transition is a vital developmental process for perennial plant
      survival. The process is precisely regulated by diverse endogenous genetic
      factors and environmental cues, but the mechanisms are not yet fully understood.
      Prunus mume is an ideal crop for bud dormancy analysis because of its early
      spring-flowering characteristics and small sequenced genome. Here, we analyzed
      the transcriptome profiles at the three endodormancy stages and natural flush
      stage using RNA sequencing combined with phytohormone and sugar content
      measurements. Significant alterations in hormone contents and carbohydrate
      metabolism have been observed, and alpha-amylases, Glucan Hydrolase Family 17 and
      diphosphate-glycosyltransferase family might play crucial roles in the
      interactions between hormones and sugars. The following hypothetical model for
      understanding the molecular mechanism of bud dormancy in Prunus mume is proposed:
      low temperatures exposure induces the significant up-regulation of eight C-repeat
      binding factor genes, which directly promotes all six dormancy-associated MADS
      box genes, resulting in dormancy establishment. The prolonged cold and/or
      subsequently increasing temperature then decreases the expression levels of these
      two gene families, which alleviates the inhibition of FLOWERING LOCUS T and
      reopens the growth-promoting pathway, resulting in dormancy release and the
      initiation of the bud break process.

PMID- 29572447
TI  - Coupling of oceanic carbon and nitrogen facilitates spatially resolved
      quantitative reconstruction of nitrate inventories.
AB  - Anthropogenic impacts are perturbing the global nitrogen cycle via warming
      effects and pollutant sources such as chemical fertilizers and burning of fossil
      fuels. Understanding controls on past nitrogen inventories might improve
      predictions for future global biogeochemical cycling. Here we show the
      quantitative reconstruction of deglacial bottom water nitrate concentrations from
      intermediate depths of the Peruvian upwelling region, using foraminiferal pore
      density. Deglacial nitrate concentrations correlate strongly with downcore
      delta13C, consistent with modern water column observations in the intermediate
      Pacific, facilitating the use of delta13C records as a paleo-nitrate-proxy at
      intermediate depths and suggesting that the carbon and nitrogen cycles were
      closely coupled throughout the last deglaciation in the Peruvian upwelling
      region. Combining the pore density and intermediate Pacific delta13C records
      shows an elevated nitrate inventory of >10% during the Last Glacial Maximum
      relative to the Holocene, consistent with a delta13C-based and delta15N-based 3D
      ocean biogeochemical model and previous box modeling studies.

PMID- 29572448
TI  - Improvement in the management of chronic obstructive pulmonary disease following
      a clinical educational program: results from a prospective cohort study in the
      Sicilian general practice setting.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder
      of the lungs associated with progressive disability. Although general
      practitioners (GPs) should play an important role in the COPD management,
      critical issues have been documented in the primary care setting. The aim of this
      study was to evaluate the effectiveness of an educational program for the
      improvement of the COPD management in a Sicilian general practice setting. The
      effectiveness of the program, was evaluated by comparing 15 quality-of-care
      indicators developed from data extracted by 33 GPs, at baseline vs. 12 and 24
      months, and compared with data from a national primary care database (HSD).
      Moreover, data on COPD-related and all-cause hospitalizations over time of COPD
      patients, was measured. Overall, 1,465 patients (3.2%) had a registered diagnosis
      of COPD at baseline vs. 1,395 (3.0%) and 1,388 (3.0%) over time (vs. 3.0% in
      HSD). COPD patients with one spirometry registered increased from 59.7% at
      baseline to 73.0% after 2 years (vs. 64.8% in HSD). Instead, some quality of care
      indicators where not modified such as proportion of COPD patients treated with
      ICS in monotherapy that was almost stable during the study period: 9.6%
      (baseline) vs. 9.9% (after 2 years), vs. 7.7% in HSD. COPD-related and all-cause
      hospitalizations of patients affected by COPD decreased during the two
      observation years (from 6.9% vs. 4.0%; from 23.0% vs. 18.9%, respectively). Our
      study showed that educational program involving specialists, clinical
      pharmacologists and GPs based on training events and clinical audit may
      contribute to partly improve both diagnostic and therapeutic management of COPD
      in primary care setting, despite this effect may vary across GPs and indicators
      of COPD quality of care.

PMID- 29572449
TI  - Genetic markers for urine haptoglobin is associated with decline in renal
      function in type 2 diabetes in East Asians.
AB  - Urine haptoglobin (uHP) level prospectively predicts diabetic kidney disease
      (DKD) progression. Here, we aim to identify genetic determinants of uHP level and
      evaluate association with renal function in East Asians (EA) with type 2 diabetes
      (T2D). Genome-wide association study (GWAS) among 805 [236 Chinese (discovery)
      and 569 (57 Malay and 512 Chinese) (validation)] found that
      rs75444904/kgp16506790 variant was robustly associated with uHP level (MetaP =
      1.21 * 10-60). rs75444904 correlates well with plasma HP protein levels and
      multimerization in EA but was not in perfect LD (r2 = 0.911 in Chinese, r2 =
      0.536 in Malay) and is monomorphic in Europeans (1000 G data). Conditional
      probability analysis indicated weakening of effects but residual significant
      associations between rs75444904 and uHP when adjusted on HP structural variant
      (MetaP = 8.22 * 10-7). The rs75444904 variant was associated with DKD progression
      (OR = 1.77, P = 0.014) independent of traditional risk factors. In an additional
      validation-cohort of EA (410 end-stage renal disease (ESRD) cases and 1308
      controls), rs75444904 was associated with ESRD (OR = 1.22, P = 0.036).
      Furthermore, increased risk of DKD progression (OR = 2.09, P = 0.007) with
      elevated uHP level through Mendelian randomisation analysis provide support for
      potential causal role of uHP in DKD progression in EA. However, further
      replication of our findings in larger study populations is warranted.

PMID- 29572450
TI  - RNA-Seq identifies genes whose proteins are transformative in the differentiation
      of cytotrophoblast to syncytiotrophoblast, in human primary villous and BeWo
      trophoblasts.
AB  - The fusion of villous cytotrophoblasts into the multinucleated
      syncytiotrophoblast is critical for the essential functions of the mammalian
      placenta. Using RNA-Seq gene expression and quantitative protein expression, we
      identified genes and their cognate proteins which are coordinately up- or down
      regulated in two cellular models of cytotrophoblast to syncytiotrophoblast
      development, human primary villous and human BeWo cytotrophoblasts. These include
      hCGbeta, TREML2, PAM, CRIP2, INHA, FLRG, SERPINF1, C17orf96, KRT17 and SAA1.
      These findings provide avenues for further understanding the mechanisms
      underlying mammalian placental synctiotrophoblast development.

PMID- 29572452
TI  - Exact results of the limited penetrable horizontal visibility graph associated to
      random time series and its application.
AB  - The limited penetrable horizontal visibility algorithm is an analysis tool that
      maps time series into complex networks and is a further development of the
      horizontal visibility algorithm. This paper presents exact results on the
      topological properties of the limited penetrable horizontal visibility graph
      associated with independent and identically distributed (i:i:d:) random series.
      We show that the i.i.d: random series maps on a limited penetrable horizontal
      visibility graph with exponential degree distribution, independent of the
      probability distribution from which the series was generated. We deduce the exact
      expressions of mean degree and clustering coefficient, demonstrate the long
      distance visibility property of the graph and perform numerical simulations to
      test the accuracy of our theoretical results. We then use the algorithm in
      several deterministic chaotic series, such as the logistic map, H'enon map,
      Lorenz system, energy price chaotic system and the real crude oil price. Our
      results show that the limited penetrable horizontal visibility algorithm is
      efficient to discriminate chaos from uncorrelated randomness and is able to
      measure the global evolution characteristics of the real time series.

PMID- 29572451
TI  - Urinary Biomarkers of Aminoglycoside-Induced Nephrotoxicity in Cystic Fibrosis:
      Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin.
AB  - Aminoglycosides are commonly used for the treatment of pulmonary exacerbations in
      patients with cystic fibrosis (CF). However, they are potentially nephrotoxic.
      This prospective observational cohort study aimed to investigate the potential
      validity of two urinary renal biomarkers, Kidney Injury Molecule-1 (KIM-1) and
      Neutrophil Gelatinase-associated Lipocalin (NGAL), in identifying aminoglycoside
      induced nephrotoxicity in children with CF. Children and young adults up to 20
      years of age with a confirmed diagnosis of CF were recruited from ten United
      Kingdom hospitals. Participants provided urine samples for measurement of KIM-1
      and NGAL concentrations, at baseline, at regular outpatient appointments, and
      before, during and after exposure to clinically-indicated treatment with the
      aminoglycoside tobramycin. 37/158 patients recruited (23.4%) received at least
      one course of IV tobramycin during the study. The median peak fold-change during
      tobramycin exposure for KIM-1 was 2.28 (IQR 2.69) and 4.02 (IQR 7.29) for NGAL,
      in the absence of serum creatinine changes. Baseline KIM-1 was positively
      associated with cumulative courses of IV aminoglycosides (R2 = 0.11; beta = 0.03;
      p < 0.0001). KIM-1, in particular, may be a useful, non-invasive, biomarker of
      acute and chronic proximal tubular injury associated with exposure to
      aminoglycosides in patients with CF, but its clinical utility needs to be further
      evaluated in prospective studies.

PMID- 29572453
TI  - Floral resource partitioning by individuals within generalised hoverfly
      pollination networks revealed by DNA metabarcoding.
AB  - Pollination is a key ecosystem service for agriculture and wider ecosystem
      function. However, most pollination studies focus on Hymenoptera, with hoverflies
      (Syrphidae) frequently treated as a single functional group. We tested this
      assumption by investigating pollen carried by eleven species of hoverfly in five
      genera, Cheilosia, Eristalis, Rhingia, Sericomyia and Volucella, using DNA
      metabarcoding. Hoverflies carried pollen from 59 plant taxa, suggesting they
      visit a wider number of plant species than previously appreciated. Most pollen
      recorded came from plant taxa frequently found at our study sites, predominantly
      Apiaceae, Cardueae, Calluna vulgaris, Rubus fruticosus agg., and Succisa
      pratensis, with hoverflies transporting pollen from 40% of entomophilous plant
      species present. Overall pollen transport network structures were generalised,
      similar to other pollination networks elsewhere. All hoverfly species were also
      generalised with few exclusive plant/hoverfly interactions. However, using the
      Jaccard Index, we found significant differences in the relative composition of
      pollen loads between hoverfly genera, except for Volucella, demonstrating some
      degree of functional complementarity. Eristalis and Sericomyia species had
      significant differences in relative pollen load composition compared to
      congeners. Our results demonstrate the range of pollens transported by hoverflies
      and the potential pollination function undertaken within this ecologically and
      morphologically diverse guild.

PMID- 29572454
TI  - First adequately-known quadrupedal sirenian from Eurasia (Eocene, Bay of Biscay,
      Huesca, northeastern Spain).
AB  - Sirenians are the only extant herbivorous mammals fully adapted to an aquatic
      lifestyle. They originated in Africa during the Paleocene from an undetermined
      clade of afrotherian mammals, and by the end of the Eocene they were widely
      distributed across the tropical latitudes. Here we introduce Sobrarbesiren
      cardieli gen. et sp. nov. It is the first adequately-known quadrupedal sirenian
      from Eurasia and the oldest record of this clade from western Europe. Fossils
      have been recovered from the middle Lutetian (SBZ15) site of Castejon de Sobrarbe
      41 (Huesca, Spain), and comprise many cranial and postcranial remains, including
      pelvic girdle and hind limb bones, from at least six sirenian individuals of
      different ontogenetic stages. Sobrarbesiren shows a suite of characters
      previously considered synapomorphies of different clades of derived sirenians,
      such as the presence of the processus retroversus of the squamosal and the
      pterygoid fossa, combined with ancestral characters such as the presence of an
      alisphenoid canal, a permanent P5, at least two sacral vertebrae, a primitive
      pelvis and functional femora and fibulae. Sobrarbesiren is recovered as the
      sister taxon of Dugongidae and represents a transitional stage of adaptation to
      aquatic life between the amphibious quadrupedal prorastomids and the aquatic
      quadrupedal protosirenids.

PMID- 29572455
TI  - Scale-up and large-scale production of Tetraselmis sp. CTP4 (Chlorophyta) for CO2
      mitigation: from an agar plate to 100-m3 industrial photobioreactors.
AB  - Industrial production of novel microalgal isolates is key to improving the
      current portfolio of available strains that are able to grow in large-scale
      production systems for different biotechnological applications, including carbon
      mitigation. In this context, Tetraselmis sp. CTP4 was successfully scaled up from
      an agar plate to 35- and 100-m3 industrial scale tubular photobioreactors (PBR).
      Growth was performed semi-continuously for 60 days in the autumn-winter season
      (17th October - 14th December). Optimisation of tubular PBR operations showed
      that improved productivities were obtained at a culture velocity of 0.65-1.35 m s
      1 and a pH set-point for CO2 injection of 8.0. Highest volumetric (0.08 +/- 0.01
      g L-1 d-1) and areal (20.3 +/- 3.2 g m-2 d-1) biomass productivities were
      attained in the 100-m3 PBR compared to those of the 35-m3 PBR (0.05 +/- 0.02 g L
      1 d-1 and 13.5 +/- 4.3 g m-2 d-1, respectively). Lipid contents were similar in
      both PBRs (9-10% of ash free dry weight). CO2 sequestration was followed in the
      100-m3 PBR, revealing a mean CO2 mitigation efficiency of 65% and a biomass to
      carbon ratio of 1.80. Tetraselmis sp. CTP4 is thus a robust candidate for
      industrial-scale production with promising biomass productivities and
      photosynthetic efficiencies up to 3.5% of total solar irradiance.

PMID- 29572456
TI  - Macular assessment of preoperative optical coherence tomography in ageing Chinese
      undergoing routine cataract surgery.
AB  - This retrospective consecutive case series aimed to evaluate spectral-domain
      optical coherence tomography (SD-OCT) for occult macular disease recognition
      preoperatively in patients scheduled for routine cataract surgery. All patients
      scheduled for cataract surgery underwent macular SD-OCT. Scans were reviewed for
      retinal, retinal pigment epithelium and vitreomacular interface abnormalities.
      For the subgroup analysis, the following information was collected: age; sex; and
      diabetes, hypertension, myopia, glaucoma, post intra-ocular surgery,
      endophotocoagulation, retinal vasculopathy and uveitis statuses. One-thousand-one
      hundred-seventy-six consecutive scans were acquired from 1,176 patients. Macular
      pathology was found in 294 eyes. The most common macular disorders were an
      epiretinal membrane (n = 130), myopia atrophy (n = 61) and a dome-shaped macular
      with pathologic myopia (n = 32). One-hundred-thirty eyes (11.05%) presented
      macular epiretinal membranes not detected by dilated fundus examination,
      accounting for 44.22% of the abnormalities in diseased eyes and was higher than
      in previous Chinese studies. Some had multiple macular disorders. The most common
      ocular history was myopia, including high myopia. The pooled prevalence rate of
      macular diseases detected by OCT was 0.24 (95% CI 0.14-0.34) using meta-analysis.
      SD-OCT should be performed for routine cataract surgery patients to evaluate
      visual outcomes, especially in myopic patients and those considering advanced
      technology intraocular lenses.

PMID- 29572457
TI  - Chitosan and cloxacillin combination improve antibiotic efficacy against
      different lifestyle of coagulase-negative Staphylococcus isolates from chronic
      bovine mastitis.
AB  - Bovine mastitis affects the health of dairy cows and the profitability of herds
      worldwide. Coagulase-negative staphylococci (CNS) are the most frequently
      isolated pathogens in bovine intramammary infection. Based on the wide range of
      antimicrobial, mucoadhesive and immunostimulant properties demonstrated by
      chitosan, we have evaluated therapy efficiency of chitosan incorporation to
      cloxacillin antibiotic as well as its effect against different bacterial
      lifestyles of seven CNS isolates from chronic intramammary infections. The
      therapeutic effects of combinations were evaluated on planktonic cultures,
      bacterial biofilms and intracellular growth in mammary epithelial cells. We found
      that biofilms and intracellular growth forms offered a strong protection against
      antibiotic therapy. On the other hand, we found that chitosan addition to
      cloxacillin efficiently reduced the antibiotic concentration necessary for
      bacterial killing in different lifestyle. Remarkably, the combined treatment was
      not only able to inhibit bacterial biofilm establishment and increase preformed
      biofilm eradication, but it also reduced intracellular bacterial viability while
      it increased IL-6 secretion by infected epithelial cells. These findings provide
      a new approach to prophylactic drying therapy that could help to improve
      conventional antimicrobial treatment against different forms of bacterial growth
      in an efficient, safer and greener manner reducing multiresistant bacteria
      generation and spread.

PMID- 29572458
TI  - Predictors of poor neonatal outcomes in prenatally diagnosed multicystic
      dysplastic kidney disease.
AB  - OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common
      anomalies detected by prenatal ultrasound. Our objective was to identify factors
      associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK
      STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009
      to 30 December 2014) from a single academic center was conducted. The primary
      outcome was death or need for dialysis among live-born infants. Associations
      between prenatal characteristics and outcome were analyzed by Fisher's exact test
      and Mann-Whitney test. RESULTS: A total of 53 cases of prenatally suspected MCDK
      were included, of which 46 cases were live-born and confirmed postnatally (38
      survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral
      MCDK, contralateral renal anomalies, and anhydramnios were significantly
      associated with death or need for dialysis (all p < 0.0001). CONCLUSIONS:
      Prenatally identified findings are associated with adverse neonatal outcome, and
      can guide counseling and management planning. In the absence of significant
      associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal
      course.

PMID- 29572459
TI  - Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824).
AB  - Pretomanid is a promising anti-tubercular drug currently at clinical phase III,
      but its mechanisms of action are currently unclear. This study aimed to: (i)
      reveal the metabolome of Mycobacterium smegmatis under pretomanid treatment; (ii)
      compare major sources of metabolite variation in bacteria treated with pretomanid
      treatment and other antibiotics; and (iii) to target metabolites responsible for
      the killing activity of pretomanid in mycobacteria. Untargeted high-resolution
      metabolite profiling was carried out using flow infusion electrospray ion high
      resolution mass spectrometry (FIE-HRMS) to identify and quantify metabolites. The
      identification of key metabolites was independently confirmed by gas
      chromatography time-of flight mass spectrometry (GC-tofMS) in comparison to
      standards. Pretomanid treatments generated a unique distinctive metabolite
      profile when compared to ampicillin, ethambutol, ethionamide, isoniazid,
      kanamycin, linezolid, rifampicin and streptomycin. Metabolites which differed
      significantly only with pretomanid treatment were identified and mapped on to
      bacterial metabolic pathways. This targeted the pentose phosphate pathway with
      significant accumulation seen with fructose-6-phosphate, ribose-5-phosphate and
      glyceraldehyde-3-phosphate. These effects were linked to the accumulation of a
      toxic metabolite methylglyoxal. This compound showed significant antimicrobial
      activity (MIC 0.65 mM) against M. smegmatis.

PMID- 29572460
TI  - Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent
      onset Type 2 Diabetes Mellitus.
AB  - We investigated the association of redox regulator Nuclear factor erythroid 2
      related factor 2 (Nrf2) and inflammatory cytokines as well as clinical remission
      in patients with recent onset type 2 diabetes (DM). Blood was collected from 180
      DM patients (105 males/75 females) and 150 control subjects (86 males/64
      females). Blood glucose, HbA1c, lipid profile and Nrf2 levels were determined
      along with circulatory cytokines in study subjects. The data were adjusted with
      confounding factors such as age and sex using multiple logistic regression
      analysis. We found that Th1/Th2 and oxidative stress markers were significantly
      elevated, whereas Nrf2 and its downstream targets were decreased in peripheral
      blood mononuclear cells (PBMCs) of DM subjects when compared with control. The
      circulatory levels of Nrf2 showed a positive correlation with Th2 cytokines and
      negative correlation to Th1 cytokines. Further, the impaired insulin secretion in
      pancreatic beta-cells observed due to cytokine stress has been restored by
      activation of Nrf2 as assessed by glucose-stimulated insulin secretion (GSIS).
      This study identifies Nrf2 plays a central role in skewing Th1 and Th2 dominance
      in the progression of diabetes.

PMID- 29572461
TI  - Dnmt3a in the dorsal dentate gyrus is a key regulator of fear renewal.
AB  - Renewal of extinguished fear memory in an altered context is widely believed to
      be a major limiting issue for exposure therapy in treating various psychiatric
      diseases. Effective prevention of fear renewal will significantly improve the
      efficacy of exposure therapy. DNA methyltransferase (DNMTs) mediated epigenetic
      processes play critical roles in long term memory, but little is known about
      their functions in fear memory extinction or renewal. Here we investigated
      whether DNMTs regulate fear renewal after extinction. We found that elevated
      Dnmt3a level in the dorsal dentate gyrus (dDG) of hippocampus was associated with
      the absence of fear renewal in an altered context after extinction training.
      Overexpression and knockdown of Dnmt3a in the dDG regulated the occurrence of
      fear renewal in a bi-directional manner. In addition, Dnmt3a overexpression was
      associated with elevated expression of c-Fos in the dDG during extinction
      training. Furthermore, we found that renewal of remote fear memory can be
      prevented, and the absence of renewal was concurrent with an elevated Dnmt3a
      level. Our results indicate that Dnmt3a in the dDG is a key regulator of fear
      renewal after extinction, and Dnmt3a may play a critical role in controlling fear
      memory return and thus has therapeutic values.

PMID- 29572462
TI  - Regulation of IL-22BP in psoriasis.
AB  - IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and in other
      inflammatory diseases. The function of IL-22 is regulated by the soluble
      scavenging receptor, IL-22 binding protein (IL-22BP or IL-22RA2). However, the
      role and regulation of IL-22BP itself in the pathogenesis of inflammatory disease
      remain unclear. We used the TLR7 agonist Imiquimod (IMQ) to induce a psoriasis
      like skin disease in mice and found a strong downregulation of IL-22BP in the
      affected skin as well as in the lymph nodes of animals treated with IMQ. We also
      analysed psoriatic skin of patients and compared this to skin of healthy donors.
      Interestingly, IL-22BP expression was similarly downregulated in skin biopsies of
      psoriasis patients compared to the skin of healthy donors. Since IL-22BP is
      expressed foremost in dendritic cells, we characterized its expression in
      monocyte-derived dendritic cells (MoDC) during maturation. In this way, we found
      Prostaglandin E2 (PGE2) to be a potent suppressor of IL-22BP expression in vitro.
      We conclude that regulation of IL-22BP by inflammatory mediators is an important
      step for the progression of inflammation in the skin and possibly also in other
      autoimmune diseases.

PMID- 29572463
TI  - Knowledge and self-reported practices of infection control among various
      occupational groups in a rural and an urban hospital in Vietnam.
AB  - Staff practice, driven by knowledge, plays a decisive role in hospital infection
      control. This study aimed to assess and compare knowledge and self-reported
      practices of infection control among various occupational groups in a rural and
      an urban hospital in Vietnam. Questionnaires consisting of items on knowledge and
      practices were collected from 339 hospital staff with varying occupations. For
      analysis, total knowledge or practice score ranged from 0-15. Mood's median test
      was performed to compare median scores. Post-hoc analysis of ordinal logistic
      regression models was applied to test differences in scores among occupational
      groups. The majority of hospital staff had good or adequate knowledge (median
      score: rural = 11.8; urban = 12), but the score range was wide (1.4-14.5). Self
      reported practices in the urban hospital were likely to be better than in the
      rural one (p = 0.003). Self-reported practices yet not completely satisfactory,
      indicating the need for continuing professional development in both settings.
      Overall, cleaners had lower scores than both physicians and nurses, highlighting
      the need for tailored education in this topic. Future infection control
      strategies within the hospitals might want to assess the difference between the
      staff's self-reported practice and their actual real practice. These findings can
      be of value in many other similar settings.

PMID- 29572464
TI  - Concurrent action of purifying selection and gene conversion results in extreme
      conservation of the major stress-inducible Hsp70 genes in mammals.
AB  - Several evolutionary mechanisms alter the fate of mutations and genes within
      populations based on their exhibited functional effects. To understand the
      underlying mechanisms involved in the evolution of the cellular stress response,
      a very conserved mechanism in the course of organismal evolution, we studied the
      patterns of natural genetic variation and functional consequences of
      polymorphisms of two stress-inducible Hsp70 genes. These genes, HSPA1A and
      HSPA1B, are major orchestrators of the cellular stress response and are
      associated with several human diseases. Our phylogenetic analyses revealed that
      the duplication of HSPA1A and HSPA1B originated in a lineage proceeding to
      placental mammals, and henceforth they remained in conserved synteny.
      Additionally, analyses of synonymous and non-synonymous changes suggest that
      purifying selection shaped the HSPA1 gene diversification, while gene conversion
      resulted in high sequence conservation within species. In the human HSPA1
      cluster, the vast majority of mutations are synonymous and specific genic regions
      are devoid of mutations. Furthermore, functional characterization of several
      human polymorphisms revealed subtle differences in HSPA1A stability and
      intracellular localization. Collectively, the observable patterns of HSPA1A-1B
      variation describe an evolutionary pattern, in which purifying selection and gene
      conversion act simultaneously and conserve a major orchestrator of the cellular
      stress response.

PMID- 29572466
TI  - Adaptive nodes enrich nonlinear cooperative learning beyond traditional
      adaptation by links.
AB  - Physical models typically assume time-independent interactions, whereas neural
      networks and machine learning incorporate interactions that function as
      adjustable parameters. Here we demonstrate a new type of abundant cooperative
      nonlinear dynamics where learning is attributed solely to the nodes, instead of
      the network links which their number is significantly larger. The nodal,
      neuronal, fast adaptation follows its relative anisotropic (dendritic) input
      timings, as indicated experimentally, similarly to the slow learning mechanism
      currently attributed to the links, synapses. It represents a non-local learning
      rule, where effectively many incoming links to a node concurrently undergo the
      same adaptation. The network dynamics is now counterintuitively governed by the
      weak links, which previously were assumed to be insignificant. This cooperative
      nonlinear dynamic adaptation presents a self-controlled mechanism to prevent
      divergence or vanishing of the learning parameters, as opposed to learning by
      links, and also supports self-oscillations of the effective learning parameters.
      It hints on a hierarchical computational complexity of nodes, following their
      number of anisotropic inputs and opens new horizons for advanced deep learning
      algorithms and artificial intelligence based applications, as well as a new
      mechanism for enhanced and fast learning by neural networks.

PMID- 29572465
TI  - Ion implantation in nanodiamonds: size effect and energy dependence.
AB  - Nanoparticles are ubiquitous in nature and are increasingly important for
      technology. They are subject to bombardment by ionizing radiation in a diverse
      range of environments. In particular, nanodiamonds represent a variety of
      nanoparticles of significant fundamental and applied interest. Here we present a
      combined experimental and computational study of the behaviour of nanodiamonds
      under irradiation by xenon ions. Unexpectedly, we observed a pronounced size
      effect on the radiation resistance of the nanodiamonds: particles larger than 8
      nm behave similarly to macroscopic diamond (i.e. characterized by high radiation
      resistance) whereas smaller particles can be completely destroyed by a single
      impact from an ion in a defined energy range. This latter observation is
      explained by extreme heating of the nanodiamonds by the penetrating ion. The
      obtained results are not limited to nanodiamonds, making them of interest for
      several fields, putting constraints on processes for the controlled modification
      of nanodiamonds, on the survival of dust in astrophysical environments, and on
      the behaviour of actinides released from nuclear waste into the environment.

PMID- 29572467
TI  - Giant thermal hysteresis in Verwey transition of single domain Fe3O4
      nanoparticles.
AB  - Most interesting phenomena of condensed matter physics originate from
      interactions among different degrees of freedom, making it a very intriguing yet
      challenging question how certain ground states emerge from only a limited number
      of atoms in assembly. This is especially the case for strongly correlated
      electron systems with overwhelming complexity. The Verwey transition of Fe3O4 is
      a classic example of this category, of which the origin is still elusive 80 years
      after the first report. Here we report, for the first time, that the Verwey
      transition of Fe3O4 nanoparticles exhibits size-dependent thermal hysteresis in
      magnetization, 57Fe NMR, and XRD measurements. The hysteresis width passes a
      maximum of 11 K when the size is 120 nm while dropping to only 1 K for the bulk
      sample. This behavior is very similar to that of magnetic coercivity and the
      critical sizes of the hysteresis and the magnetic single domain are identical. We
      interpret it as a manifestation of charge ordering and spin ordering correlation
      in a single domain. This work paves a new way of undertaking researches in the
      vibrant field of strongly correlated electron physics combined with nanoscience.

PMID- 29572468
TI  - Impact of spatial organization on a novel auxotrophic interaction among soil
      microbes.
AB  - A key prerequisite to achieve a deeper understanding of microbial communities and
      to engineer synthetic ones is to identify the individual metabolic interactions
      among key species and how these interactions are affected by different
      environmental factors. Deciphering the physiological basis of species-species and
      species-environment interactions in spatially organized environments requires
      reductionist approaches using ecologically and functionally relevant species. To
      this end, we focus here on a defined system to study the metabolic interactions
      in a spatial context among the plant-beneficial endophytic fungus Serendipita
      indica, and the soil-dwelling model bacterium Bacillus subtilis. Focusing on the
      growth dynamics of S. indica under defined conditions, we identified an
      auxotrophy in this organism for thiamine, which is a key co-factor for essential
      reactions in the central carbon metabolism. We found that S. indica growth is
      restored in thiamine-free media, when co-cultured with B. subtilis. The success
      of this auxotrophic interaction, however, was dependent on the spatial and
      temporal organization of the system; the beneficial impact of B. subtilis was
      only visible when its inoculation was separated from that of S. indica either in
      time or space. These findings describe a key auxotrophic interaction in the soil
      among organisms that are shown to be important for plant ecosystem functioning,
      and point to the potential importance of spatial and temporal organization for
      the success of auxotrophic interactions. These points can be particularly
      important for engineering of minimal functional synthetic communities as plant
      seed treatments and for vertical farming under defined conditions.

PMID- 29572469
TI  - A new hybrid approach for MHC genotyping: high-throughput NGS and long read
      MinION nanopore sequencing, with application to the non-model vertebrate Alpine
      chamois (Rupicapra rupicapra).
AB  - The major histocompatibility complex (MHC) acts as an interface between the
      immune system and infectious diseases. Accurate characterization and genotyping
      of the extremely variable MHC loci are challenging especially without a reference
      sequence. We designed a combination of long-range PCR, Illumina short-reads, and
      Oxford Nanopore MinION long-reads approaches to capture the genetic variation of
      the MHC II DRB locus in an Italian population of the Alpine chamois (Rupicapra
      rupicapra). We utilized long-range PCR to generate a 9 Kb fragment of the DRB
      locus. Amplicons from six different individuals were fragmented, tagged, and
      simultaneously sequenced with Illumina MiSeq. One of these amplicons was
      sequenced with the MinION device, which produced long reads covering the entire
      amplified fragment. A pipeline that combines short and long reads resolved
      several short tandem repeats and homopolymers and produced a de novo reference,
      which was then used to map and genotype the short reads from all individuals. The
      assembled DRB locus showed a high level of polymorphism and the presence of a
      recombination breakpoint. Our results suggest that an amplicon-based NGS approach
      coupled with single-molecule MinION nanopore sequencing can efficiently achieve
      both the assembly and the genotyping of complex genomic regions in multiple
      individuals in the absence of a reference sequence.

PMID- 29572470
TI  - Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1
      infection and increased activity post-vaccination.
AB  - Natural killer (NK) cells limit viral replication by direct recognition of
      infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing
      cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1
      infection, further knowledge of their response is necessary. Here we show that NK
      cells responding to models of direct cell recognition, ADCC, and cytokine
      activation have unique transcriptional fingerprints. Compared with healthy
      volunteers, individuals with chronic HIV-1 infection have higher expression of
      genes commonly associated with activation, and lower expression of genes
      associated with direct cell recognition and cytokine stimulation in their NK
      cells. By contrast, NK cell transcriptional profiles of individuals receiving a
      modified vaccinia Ankara (MVA) vectored HIV-1 vaccine show upregulation of genes
      associated with direct cell recognition. These findings demonstrate that targeted
      transcriptional profiling provides a sensitive assessment of NK cell activity,
      which helps understand how NK cells respond to viral infections and vaccination.

PMID- 29572471
TI  - BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy
      for treating systemic lupus erythematosus.
AB  - BAFF, a member of the TNF superfamily, has been recognized as a good target for
      autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by
      the FDA for use in treating systemic lupus erythematosus. However, the molecular
      basis of BAFF neutralization by belimumab remains unclear. Here our crystal
      structure of the BAFF-belimumab Fab complex shows the precise epitope and the
      BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic
      activity of belimumab involves not only antagonizing the BAFF-receptor
      interaction, but also disrupting the formation of the more active BAFF 60-mer to
      favor the induction of the less active BAFF trimer through interaction with the
      flap region of BAFF. In addition, the belimumab HCDR3 loop mimics the DxL(V/L)
      motif of BAFF receptors, thereby binding to BAFF in a similar manner as
      endogenous BAFF receptors. Our data thus provides insights for the design of new
      drugs targeting BAFF for the treatment of autoimmune diseases.

PMID- 29572472
TI  - Diversity of innate immune cell subsets across spatial and temporal scales in an
      EAE mouse model.
AB  - In both multiple sclerosis and its model experimental autoimmune
      encephalomyelitis (EAE), the extent of resident microglia activation and
      infiltration of monocyte-derived cells to the CNS is positively correlated to
      tissue damage. To address the phenotype characterization of different cell
      subsets, their spatio-temporal distributions and contributions to disease
      development we induced EAE in Thy1-CFP//LysM-EGFP//CD11c-EYFP reporter mice. We
      combined high content flow cytometry, immunofluorescence and two-photon imaging
      in live mice and identified a stepwise program of inflammatory cells
      accumulation. First on day 10 after induction, EGFP+ neutrophils and monocytes
      invade the spinal cord parenchyma through the meninges rather than by
      extravasion. This event occurs just before axonal losses in the white matter.
      Once in the parenchyma, monocytes mature into EGFP+/EYFP+ monocyte-derived
      dendritic cells (moDCs) whose density is maximal on day 17 when the axonal
      degradation and clinical signs stabilize. Meanwhile, microglia is progressively
      activated in the grey matter and subsequently recruited to plaques to phagocyte
      axon debris. LysM-EGFP//CD11c-EYFP mice appear as a powerful tool to
      differentiate moDCs from macrophages and to study the dynamics of immune cell
      maturation and phenotypic evolution in EAE.

PMID- 29572473
TI  - Lactobacillus paracasei CNCM I-3689 reduces vancomycin-resistant Enterococcus
      persistence and promotes Bacteroidetes resilience in the gut following antibiotic
      challenge.
AB  - Enterococci, in particular vancomycin-resistant enterococci (VRE), are a leading
      cause of hospital-acquired infections. Promoting intestinal resistance against
      enterococci could reduce the risk of VRE infections. We investigated the effects
      of two Lactobacillus strains to prevent intestinal VRE. We used an intestinal
      colonisation mouse model based on an antibiotic-induced microbiota dysbiosis to
      mimic enterococci overgrowth and VRE persistence. Each Lactobacillus spp. was
      administered daily to mice starting one week before antibiotic treatment until
      two weeks after antibiotic and VRE inoculation. Of the two strains, Lactobacillus
      paracasei CNCM I-3689 decreased significantly VRE numbers in the feces
      demonstrating an improvement of the reduction of VRE. Longitudinal microbiota
      analysis showed that supplementation with L. paracasei CNCM I-3689 was associated
      with a better recovery of members of the phylum Bacteroidetes. Bile salt analysis
      and expression analysis of selected host genes revealed increased level of
      lithocholate and of ileal expression of camp (human LL-37) upon L. paracasei CNCM
      I-3689 supplementation. Although a direct effect of L. paracasei CNCM I-3689 on
      the VRE reduction was not ruled out, our data provide clues to possible anti-VRE
      mechanisms supporting an indirect anti-VRE effect through the gut microbiota.
      This work sustains non-antibiotic strategies against opportunistic enterococci
      after antibiotic-induced dysbiosis.

PMID- 29572474
TI  - Ecological control of nitrite in the upper ocean.
AB  - Microorganisms oxidize organic nitrogen to nitrate in a series of steps. Nitrite,
      an intermediate product, accumulates at the base of the sunlit layer in the
      subtropical ocean, forming a primary nitrite maximum, but can accumulate
      throughout the sunlit layer at higher latitudes. We model nitrifying
      chemoautotrophs in a marine ecosystem and demonstrate that microbial community
      interactions can explain the nitrite distributions. Our theoretical framework
      proposes that nitrite can accumulate to a higher concentration than ammonium
      because of differences in underlying redox chemistry and cell size between
      ammonia- and nitrite-oxidizing chemoautotrophs. Using ocean circulation models,
      we demonstrate that nitrifying microorganisms are excluded in the sunlit layer
      when phytoplankton are nitrogen-limited, but thrive at depth when phytoplankton
      become light-limited, resulting in nitrite accumulation there. However,
      nitrifying microorganisms may coexist in the sunlit layer when phytoplankton are
      iron- or light-limited (often in higher latitudes). These results improve
      understanding of the controls on nitrification, and provide a framework for
      representing chemoautotrophs and their biogeochemical effects in ocean models.

PMID- 29572475
TI  - Structure and evolution of the Fam20 kinases.
AB  - The Fam20 proteins are novel kinases that phosphorylate secreted proteins and
      proteoglycans. Fam20C phosphorylates hundreds of secreted proteins and is
      activated by the pseudokinase Fam20A. Fam20B phosphorylates a xylose residue to
      regulate proteoglycan synthesis. Despite these wide-ranging and important
      functions, the molecular and structural basis for the regulation and substrate
      specificity of these kinases are unknown. Here we report molecular
      characterizations of all three Fam20 kinases, and show that Fam20C is activated
      by the formation of an evolutionarily conserved homodimer or heterodimer with
      Fam20A. Fam20B has a unique active site for recognizing Galbeta1-4Xylbeta1, the
      initiator disaccharide within the tetrasaccharide linker region of proteoglycans.
      We further show that in animals the monomeric Fam20B preceded the appearance of
      the dimeric Fam20C, and the dimerization trait of Fam20C emerged concomitantly
      with a change in substrate specificity. Our results provide comprehensive
      structural, biochemical, and evolutionary insights into the function of the Fam20
      kinases.

PMID- 29572476
TI  - Linear and inverted U-shaped dose-response functions describe estrogen effects on
      hippocampal activity in young women.
AB  - In animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose
      dependent, monotonically increasing manner, but this relationship can also
      exhibit an inverted U-shaped function. To investigate E2's dose-response function
      in the human hippocampus, we pharmacologically increased E2 levels in 125
      naturally cycling women (who were in their low-hormone menstruation phase) to
      physiological (equivalent to menstrual cycle peak) and supraphysiological
      (equivalent to levels during early pregnancy) concentrations in a placebo
      controlled design. Twenty-four hours after first E2 intake, we measured brain
      activity during encoding of neutral and negative pictures and then tested
      recognition memory 24 h after encoding. Here we report that E2 exhibits both a
      monotonically increasing relationship with hippocampal activity as well as an
      inverted U-shaped relationship, depending on the hippocampal region. Hippocampal
      activity exhibiting a U-shaped relationship inflects at supraphysiological E2
      levels, suggesting that while E2 within physiological ranges stimulates
      hippocampal activity, supraphysiological ranges show opposite effects.

PMID- 29572477
TI  - Mechanism of action of the third generation benzopyrans and evaluation of their
      broad anti-cancer activity in vitro and in vivo.
AB  - Successive rounds of chemical modification in three generations of benzopyran
      molecules have shown to select for different mechanisms of actions and
      progressive increases in anti-cancer activity. In this study, we investigated the
      mechanism of action of the third-generation benzopyran compounds, TRX-E-002-1 and
      TRX-E-009-1. High-content screening of a panel of 240 cancer cell lines treated
      with TRX-E-009-1 demonstrated it has broad anti-cancer potential. Within this
      screen, melanoma cell lines showed a range of sensitivities and subsequently a
      second independent panel of 21 melanoma 3D spheroid lines were assessed for their
      responses to both TRX-E-002-1 and TRX-E-009-1 compounds. Time-lapse microscopy
      illustrated both of these compounds caused mitotic delays in treated cells,
      resulting in either mitotic slippage or apoptosis. This finding along with
      immunostaining, in vitro polymerization assays, and animal experiments in both
      athymic and immunocompetent mice, demonstrates that these third-generation
      benzopyran compounds are potent tubulin polymerization inhibitors in vitro and in
      vivo, and this is the molecular basis of their anti-cancer activity in melanoma.
      These findings indicate these BP compounds may offer a novel anti-microtubule
      strategy for cancer intervention and provides the basis for further investigation
      into biomarkers of clinical sensitivity.

PMID- 29572478
TI  - Increased Levels of Cardiac Troponin I in Subjects with Extremely Low B-type
      Natriuretic Peptide Levels.
AB  - Because of the lack of studies focused on the biological implications of
      extremely low B-type natriuretic peptide (BNP) levels, we investigated whether
      extremely low BNP levels could be harmful to the cardiovascular system due to
      compromised cardio-protection. By using cardiac troponin I (cTnI) as an indicator
      of cardiovascular disorder, we assessed whether cTnI was inversely associated
      with BNP in populations with low BNP levels. A total of 2,001 apparently healthy
      subjects older than 38 years were included in this study. We defined subgroups
      from this population by limiting the maximum BNP level with cut-off values
      ranging from 1 through 20 pg/mL and performed covariance structure analyses by
      comparing log(BNP) with log(cTnI) in each subgroup. The beta values between
      log(BNP) and log(cTnI) sharply decreased as the BNP cut-off was reduced from 20
      pg/mL (beta = 0.04) to 1 pg/mL (beta = -0.29) and became significant when the BNP
      cut-off levels were lower than 4 pg/mL (p < 0.005). In subgroups with BNP levels
      lower than 4 pg/mL, elevation in cTnI level was inversely associated with BNP (p
      < 0.005), which suggests that insufficient BNP may play a pathogenic role in the
      occurrence of cardiovascular abnormalities.

PMID- 29572479
TI  - Cut Based Method for Comparing Complex Networks.
AB  - Revealing the underlying similarity of various complex networks has become both a
      popular and interdisciplinary topic, with a plethora of relevant application
      domains. The essence of the similarity here is that network features of the same
      network type are highly similar, while the features of different kinds of
      networks present low similarity. In this paper, we introduce and explore a new
      method for comparing various complex networks based on the cut distance. We show
      correspondence between the cut distance and the similarity of two networks. This
      correspondence allows us to consider a broad range of complex networks and
      explicitly compare various networks with high accuracy. Various machine learning
      technologies such as genetic algorithms, nearest neighbor classification, and
      model selection are employed during the comparison process. Our cut method is
      shown to be suited for comparisons of undirected networks and directed networks,
      as well as weighted networks. In the model selection process, the results
      demonstrate that our approach outperforms other state-of-the-art methods with
      respect to accuracy.

PMID- 29572480
TI  - Brain activations associated with fearful experience show common and distinct
      patterns between younger and older adults in the hippocampus and the amygdala.
AB  - Revisiting threat-related scenes elicits fear and activates a brain network
      related to cognitive-affective processing. Prior experience may contribute to the
      present fearful experience. We aimed to investigate (a) patterns of brain
      activation associated with individual differences in past fearful experiences
      (pFear) and the present fear elicited by watching videos (eFear) and (b) age
      related differences in the activation patterns. Forty healthy adults, including
      20 younger adults (YA) and 20 older adults (OA), underwent functional magnetic
      resonance imaging while watching videos containing high- and low-threat scenes of
      medical treatment. Both age subgroups showed positive correlations between pFear
      and bilateral hippocampal activation. Only YA showed threat-related activation in
      the bilateral anterior insula and activation positively correlated with pFear in
      the bilateral S1 and the amygdala. The evidence suggests that the hippocampus,
      amygdala and S1 may play key roles in bridging past fearful experiences and the
      present fear elicited by revisiting visual scenes and that the interaction
      between memory and emotional processing may be age dependent.

PMID- 29572481
TI  - Tibial Osteotomy as a Mechanical Model of Primary Osteoarthritis in Rats.
AB  - This study has presented the first purely biomechanical surgical model of
      osteoarthritis (OA) in rats, which could be more representative of the human
      primary disease than intra-articular techniques published previously. A surgical
      tibial osteotomy (TO) was used to induce degenerative cartilage changes in the
      medial knee of Sprague-Dawley rats. The presence of osteoarthritic changes in the
      medial knee compartment of the operated animals was evaluated histologically and
      through analysis of serum carboxy-terminal telepeptides of type II collagen (CTX
      II). In-vivo biomechanical analyses were carried out using a musculoskeletal
      model of the rat hindlimb to evaluate the loading conditions in the knee pre and
      post-surgically. Qualitative and quantitative medial cartilage degeneration
      consistent with OA was found in the knees of the operated animals alongside
      elevated CTX-II levels and increased tibial compressive loading. The potential
      avoidance of joint inflammation post-surgically, the maintenance of internal
      joint biomechanics and the ability to quantify the alterations in joint loading
      should make this model of OA a better candidate for modeling primary forms of the
      disease in humans.

PMID- 29572482
TI  - Bacteriophages are more virulent to bacteria with human cells than they are in
      bacterial culture; insights from HT-29 cells.
AB  - Bacteriophage therapeutic development will clearly benefit from understanding the
      fundamental dynamics of in vivo phage-bacteria interactions. Such information can
      inform animal and human trials, and much can be ascertained from human cell-line
      work. We have developed a human cell-based system using Clostridium difficile, a
      pernicious hospital pathogen with limited treatment options, and the phage
      phiCDHS1 that effectively kills this bacterium in liquid culture. The human colon
      tumorigenic cell line HT-29 was used because it simulates the colon environment
      where C. difficile infection occurs. Studies on the dynamics of phage-bacteria
      interactions revealed novel facets of phage biology, showing that phage can
      reduce C. difficile numbers more effectively in the presence of HT-29 cells than
      in vitro. Both planktonic and adhered Clostridial cell numbers were successfully
      reduced. We hypothesise and demonstrate that this observation is due to strong
      phage adsorption to the HT-29 cells, which likely promotes phage-bacteria
      interactions. The data also showed that the phage phiCDHS1 was not toxic to HT-29
      cells, and phage-mediated bacterial lysis did not cause toxin release and
      cytotoxic effects. The use of human cell lines to understand phage-bacterial
      dynamics offers valuable insights into phage biology in vivo, and can provide
      informative data for human trials.

PMID- 29572484
TI  - Phthalate metabolite exposures among immigrants living in the United States:
      findings from NHANES, 1999-2014.
AB  - Phthalates exposure has been linked to multiple health risks, and US immigrants
      may have different exposures to phthalates due to lifestyle differences. Urinary
      concentrations of eight phthalate metabolites (mono-ethyl phthalate [MEP], mono-n
      butyl phthalate [MnBP], mono-isobutyl phthalate [MiBP], mono-(3-carboxypropyl)
      phthalate [MCPP], mono-benzyl phthalate [MBzP], mono-2-ethylhexyl phthalate
      [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5
      oxohexyl) phthalate [MEOHP]) were measured in 10318 US-born and 3511 foreign-born
      individuals from NHANES 1999-2014. Using multivariate adjusted linear regression,
      we assessed whether phthalate metabolite levels differed by nativity in the whole
      population, within racial/ethnic groups, and by years in the US. We also tested
      whether immigrant demographics predicted phthalate metabolite levels. In fully
      adjusted models, MEP, MnBP, and MiBP were significantly higher, and MBzP
      significantly lower, among immigrants than US-born participants. Among
      immigrants, MnBP and MiBP significantly declined with longer time in the US
      (Ptrend = 0.029 and Ptrend = 0.039, respectively), while MCPP and MBzP
      significantly rose (Ptrend = 0.019 and Ptrend = 0.043, respectively). Results
      within each racial/ethnic group were consistent with the whole population. Among
      immigrants, women had significantly higher metabolite levels than men (all p <
      0.01), and MEP, MnBP, and MCPP differed by race/ethnicity. Due to higher
      phthalate exposures, immigrants may be especially vulnerable to phthalate
      associated health problems.

PMID- 29572483
TI  - The orphan GPR50 receptor promotes constitutive TGFbeta receptor signaling and
      protects against cancer development.
AB  - Transforming growth factor-beta (TGFbeta) signaling is initiated by the type I,
      II TGFbeta receptor (TbetaRI/TbetaRII) complex. Here we report the formation of
      an alternative complex between TbetaRI and the orphan GPR50, belonging to the G
      protein-coupled receptor super-family. The interaction of GPR50 with TbetaRI
      induces spontaneous TbetaRI-dependent Smad and non-Smad signaling by stabilizing
      the active TbetaRI conformation and competing for the binding of the negative
      regulator FKBP12 to TbetaRI. GPR50 overexpression in MDA-MB-231 cells mimics the
      anti-proliferative effect of TbetaRI and decreases tumor growth in a xenograft
      mouse model. Inversely, targeted deletion of GPR50 in the MMTV/Neu spontaneous
      mammary cancer model shows decreased survival after tumor onset and increased
      tumor growth. Low GPR50 expression is associated with poor survival prognosis in
      human breast cancer irrespective of the breast cancer subtype. This describes a
      previously unappreciated spontaneous TGFbeta-independent activation mode of
      TbetaRI and identifies GPR50 as a TbetaRI co-receptor with potential impact on
      cancer development.

PMID- 29572485
TI  - Degradation of blue-phosphorescent organic light-emitting devices involves
      exciton-induced generation of polaron pair within emitting layers.
AB  - Degradation of organic materials is responsible for the short operation lifetimes
      of organic light-emitting devices, but the mechanism by which such degradation is
      initiated has yet to be fully established. Here we report a new mechanism for
      degradation of emitting layers in blue-phosphorescent devices. We investigate
      binary mixtures of a wide bandgap host and a series of novel Ir(III) complex
      dopants having N-heterocyclocarbenic ligands. Our mechanistic study reveals the
      charge-neutral generation of polaron pairs (radical ion pairs) by electron
      transfer from the dopant to host excitons. Annihilation of the radical ion pair
      occurs by charge recombination, with such annihilation competing with bond
      scission. Device lifetime correlates linearly with the rate constant for the
      annihilation of the radical ion pair. Our findings demonstrate the importance of
      controlling exciton-induced electron transfer, and provide novel strategies to
      design materials for long-lifetime blue electrophosphorescence devices.

PMID- 29572486
TI  - SETD2 - linking stem cell survival and transformation.

PMID- 29572487
TI  - Author Correction: KRAB-type zinc-finger proteins PITA and PISA specifically
      regulate p53-dependent glycolysis and mitochondrial respiration.
AB  - We apologize for an error that we just found in the paper published online on 21
      February 2018. The 1st row/1st column of Figure 8G (PITA Normal) was
      inadvertently duplicated from 2nd row/1st column of Figure 8I (PISA Adjacent
      colonic mucosa). The 2nd row/1st column of Figure 8G (PISA Normal) was
      inadvertently duplicated from 2nd row/2nd column of Figure 8G (PISA Distal
      colonic mucosa). A corrected version of Figure 8G is provided below. No
      conclusion was affected by this error, but we apologize for not detecting it
      before publication and any inconvenience caused.

PMID- 29572488
TI  - Ubiquitin-induced phase separation of p62/SQSTM1.

PMID- 29572489
TI  - Iron regulatory protein deficiency compromises mitochondrial function in murine
      embryonic fibroblasts.
AB  - Iron is essential for growth and proliferation of mammalian cells. The
      maintenance of cellular iron homeostasis is regulated by iron regulatory proteins
      (IRPs) through binding to the cognate iron-responsive elements in target mRNAs
      and thereby regulating the expression of target genes. Irp1 or Irp2-null mutation
      is known to reduce the cellular iron level by decreasing transferrin receptor 1
      and increasing ferritin. Here, we report that Irp1 or Irp2-null mutation also
      causes downregulation of frataxin and IscU, two of the core components in the
      iron-sulfur cluster biogenesis machinery. Interestingly, while the activities of
      some of iron-sulfur cluster-containing enzymes including mitochondrial aconitase
      and cytosolic xanthine oxidase were not affected by the mutations, the activities
      of respiratory chain complexes were drastically diminished resulting in
      mitochondrial dysfunction. Overexpression of human ISCU and frataxin in Irp1 or
      Irp2-null cells was able to rescue the defects in iron-sulfur cluster biogenesis
      and mitochondrial quality. Our results strongly suggest that iron regulatory
      proteins regulate the part of iron sulfur cluster biogenesis tailored
      specifically for mitochondrial electron transport chain complexes.

PMID- 29572490
TI  - Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions
      without developing progeria.
AB  - Replication of mammalian mitochondrial DNA (mtDNA) is an essential process that
      requires high fidelity and control at multiple levels to ensure proper
      mitochondrial function. Mutations in the mitochondrial genome maintenance
      exonuclease 1 (MGME1) gene were recently reported in mitochondrial disease
      patients. Here, to study disease pathophysiology, we generated Mgme1 knockout
      mice and report that homozygous knockouts develop depletion and multiple
      deletions of mtDNA. The mtDNA replication stalling phenotypes vary dramatically
      in different tissues of Mgme1 knockout mice. Mice with MGME1 deficiency
      accumulate a long linear subgenomic mtDNA species, similar to the one found in
      mtDNA mutator mice, but do not develop progeria. This finding resolves a long
      standing debate by showing that point mutations of mtDNA are the main cause of
      progeria in mtDNA mutator mice. We also propose a role for MGME1 in the
      regulation of replication and transcription termination at the end of the control
      region of mtDNA.

PMID- 29572491
TI  - The impacts of regional transport and meteorological factors on aerosol optical
      depth over Beijing, 1980-2014.
AB  - Understanding the role of different sources that contribute to the aerosol
      extinction coefficient is an important aspect toward analyzing climate change and
      regional air quality. In Beijing specifically, the region has suffered severe air
      quality deterioration over the past three decades, but the magnitude of
      extraneous contributions to aerosol variation has remained uncertain. Therefore,
      we estimated trends of contributions to aerosol optical depth (AOD) for Beijing
      from 1980 to 2014 and built a seasonal regression model to decouple the
      extraneous contribution from the total emitted using ground-based aerosol and
      meteorological measurements, extended to the emissions of man-made and natural
      contribution. The variation of AOD over Beijing was significantly affected by the
      anthropogenic aerosol emissions, which experienced slight augmentation by 15.3%
      from 1980 to 2000, rapid inflation by 36.9% from 2000 to 2006, and a gradual
      decrease by 10.0% from 2006 to 2014. The extraneous contribution from wind and
      its associated languishing patterns explain the historical increase of regional
      AOD, which experienced about a 10% enhancement over the three stages. Other
      meteorological contributions show no significant trends over 35 years, except for
      the temperature inversion, which despite the weakened hygroscopic growth after
      2006, still experiences a significant enhancement.

PMID- 29572493
TI  - Evidence for Layered Quantized Transport in Dirac Semimetal ZrTe5.
AB  - ZrTe5 is an important semiconductor thermoelectric material and a candidate
      topological insulator. Here we report the observation of Shubnikov-de Hass (SdH)
      oscillations accompanied by quantized Hall resistance in bulk ZrTe5 crystal, with
      a mobility of 41,000 cm2V-1s-1. We have found that the quantum oscillations does
      not originate from the surface states, but from the bulk states. Each single
      layer ZrTe5 acted like an independent 2D electron system in the quantum Hall
      regime having the same carrier density and mobilities, while the bulk of the
      sample exhibits a multilayered quantum Hall effect.

PMID- 29572492
TI  - Radiomic MRI signature reveals three distinct subtypes of glioblastoma with
      different clinical and molecular characteristics, offering prognostic value
      beyond IDH1.
AB  - The remarkable heterogeneity of glioblastoma, across patients and over time, is
      one of the main challenges in precision diagnostics and treatment planning. Non
      invasive in vivo characterization of this heterogeneity using imaging could
      assist in understanding disease subtypes, as well as in risk-stratification and
      treatment planning of glioblastoma. The current study leveraged advanced imaging
      analytics and radiomic approaches applied to multi-parametric MRI of de novo
      glioblastoma patients (n = 208 discovery, n = 53 replication), and discovered
      three distinct and reproducible imaging subtypes of glioblastoma, with
      differential clinical outcome and underlying molecular characteristics, including
      isocitrate dehydrogenase-1 (IDH1), O6-methylguanine-DNA methyltransferase,
      epidermal growth factor receptor variant III (EGFRvIII), and transcriptomic
      subtype composition. The subtypes provided risk-stratification substantially
      beyond that provided by WHO classifications. Within IDH1-wildtype tumors, our
      subtypes revealed different survival (p < 0.001), thereby highlighting the
      synergistic consideration of molecular and imaging measures for prognostication.
      Moreover, the imaging characteristics suggest that subtype-specific treatment of
      peritumoral infiltrated brain tissue might be more effective than current uniform
      standard-of-care. Finally, our analysis found subtype-specific radiogenomic
      signatures of EGFRvIII-mutated tumors. The identified subtypes and their clinical
      and molecular correlates provide an in vivo portrait of phenotypic heterogeneity
      in glioblastoma, which points to the need for precision diagnostics and
      personalized treatment.

PMID- 29572494
TI  - Mechanically Reconfigurable Single-Arm Spiral Antenna Array for Generation of
      Broadband Circularly Polarized Orbital Angular Momentum Vortex Waves.
AB  - In this paper, a mechanically reconfigurable circular array with single-arm
      spiral antennas (SASAs) is designed, fabricated, and experimentally demonstrated
      to generate broadband circularly polarized orbital angular momentum (OAM) vortex
      waves in radio frequency domain. With the symmetrical and broadband properties of
      single-arm spiral antennas, the vortex waves with different OAM modes can be
      mechanically reconfigurable generated in a wide band from 3.4 GHz to 4.7 GHz. The
      prototype of the circular array is proposed, conducted, and fabricated to
      validate the theoretical analysis. The simulated and experimental results verify
      that different OAM modes can be effectively generated by rotating the spiral arms
      of single-arm spiral antennas with corresponding degrees, which greatly simplify
      the feeding network. The proposed method paves a reconfigurable way to generate
      multiple OAM vortex waves with spin angular momentum (SAM) in radio and microwave
      satellite communication applications.

PMID- 29572495
TI  - High conversion synthesis of <10 nm starch-stabilized silver nanoparticles using
      microwave technology.
AB  - A microwave reaction to convert 99 +/- 1% of Ag+ to silver nanoparticles (AgNPs)
      of size <10 nm within 4.5 min with a specific production rate and energy input of
      5.75 mg AgNP L-1 min-1 and 5.45 W mL-1 reaction volume was developed. The glucose
      reduced and food grade starch stabilized particles remained colloidally stable
      with less than a 4% change in the surface plasmon resonance band at 425-430 nm at
      t > 300 days. TEM determined the size of AgNPs, while TEM-EDS and XRD verified
      elemental composition. The conversion was determined by inductively coupled
      plasma atomic emission spectroscopy (ICP-AES) and thermal gravimetric analysis
      (TGA). Additionally, the required silver to starch input mass ratio, 1.0:1.3, to
      produce colloidally stabilized AgNPs is significantly reduced compared to
      previous studies. The antibacterial activity of freshly prepared AgNPs and AgNPs
      aged >300 days was demonstrated against E. coli as determined by agar diffusion
      assays. This result, corroborated by spectrophotometric and TEM measurements,
      indicates long-term colloidal stability of the product. Thus, this study
      sustainably produced antibacterial AgNPs from minimal inputs. In the broader
      context, the current work has quantified a sustainable platform technology to
      produce sphere-like inorganic nanoparticles with antimicrobial properties.

PMID- 29572496
TI  - Optical Detection of Degraded Therapeutic Proteins.
AB  - The quality of therapeutic proteins such as hormones, subunit and conjugate
      vaccines, and antibodies is critical to the safety and efficacy of modern
      medicine. Identifying malformed proteins at the point-of-care can prevent adverse
      immune reactions in patients; this is of special concern when there is an
      insecure supply chain resulting in the delivery of degraded, or even counterfeit,
      drug product. Identification of degraded protein, for example human growth
      hormone, is demonstrated by applying automated anomaly detection algorithms.
      Detection of the degraded protein differs from previous applications of machine
      learning and classification to spectral analysis: only example spectra of
      genuine, high-quality drug products are used to construct the classifier. The
      algorithm is tested on Raman spectra acquired on protein dilutions typical of
      formulated drug product and at sample volumes of 25 uL, below the typical
      overfill (waste) volumes present in vials of injectable drug product. The
      algorithm is demonstrated to correctly classify anomalous recombinant human
      growth hormone (rhGH) with 92% sensitivity and 98% specificity even when the
      algorithm has only previously encountered high-quality drug product.

PMID- 29572497
TI  - Use of implanted acoustic tags to assess platypus movement behaviour across
      spatial and temporal scales.
AB  - The platypus (Ornithorhynchus anatinus) is an evolutionarily distinct mammal,
      endemic to Australian freshwaters. Many aspects of its ecology and life-history,
      including detailed understanding of movements, are poorly known, hampered by its
      cryptic and mainly nocturnal habits and small numbers. We effectively trialled
      intraperitoneal implanted acoustic transmitters in nine platypuses in the Severn
      River (NSW), Australia, as a potential approach for studying movements in this
      challenging species. We tracked platypus movements over six months, at fine and
      broad spatial scales, using an array of acoustic sensors. Over six months (March
      August 2016), four of five adult platypuses (two females?three males) maintained
      localized movements (average monthly maximums 0.37 km +/- 0.03 sd), while one
      adult, one sub-adult, and one juvenile (males) moved further: average monthly
      maxima 1.2 km +/- 2.0 sd, 0.9 km +/- 0.6 sd, 4.5 km +/- 5.9 sd, respectively. The
      longest recorded movement was by a male adult, covering 11.1 km in three days and
      travelling a maximum distance of about 13 km between records. Only one implanted
      animal was not detected immediately after release, indicative of transmission
      failure rather than an adverse event. High cumulative daily movements (daily 1.9
      km +/- 0.8 sd) indicated high metabolic requirements, with implications for
      previous estimates of platypus abundances and carrying capacities, essential for
      effective conservation. This novel approach offers new avenues to investigate
      relating to mating, nesting, and intraspecific competition behaviours and their
      temporal and spatial variation.

PMID- 29572499
TI  - Correspondence: Challenging a proposed role for TRPC5 in aortic baroreceptor
      pressure-sensing.

PMID- 29572498
TI  - A single high-fat meal provokes pathological erythrocyte remodeling and increases
      myeloperoxidase levels: implications for acute coronary syndrome.
AB  - High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial
      infarction in patients with atherosclerosis, but the mechanisms are poorly
      understood. Erythrocytes (red blood cells, RBCs) intimately interact with
      inflammatory cells and blood vessels and play a complex role in regulating
      vascular function. Chronic high-fat feeding in mice induces pathological RBC
      remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction.
      However, whether acute HFM can induce RBC remodeling in humans is unknown. Ten
      healthy individuals were subjected to biochemical testing and assessment of
      endothelial-dependent flow-mediated dilation (FMD) before and after a single HFM
      or iso-caloric meal (ICM). Following the HFM, triglyceride, cholesterol, and free
      fatty acid levels were all significantly increased, in conjunction with impaired
      post-prandial FMD. Additionally, peripheral blood smears demonstrated microcytes,
      remodeled RBCs, and fatty monocytes. Increased intracellular ROS and nitration of
      protein band 3 was detected in RBCs following the HFM. The HFM elevated plasma
      and RBC-bound myeloperoxidase (MPO), which was associated with impaired FMD and
      oxidation of HDL. Monocytic cells exposed to lipid in vitro released MPO, while
      porcine coronary arteries exposed to fatty acids ex vivo took up MPO. We
      demonstrate in humans that a single HFM induces pathological RBC remodeling and
      concurrently elevates MPO, which can potentially enter the blood vessel wall to
      trigger oxidative stress and destabilize vulnerable plaques. These novel findings
      may have implications for the short-term risk of HFM consumption and alimentary
      lipemia in patients with atherosclerosis.

PMID- 29572500
TI  - Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe
      bleeding after starting therapy.
AB  - Severe hemorrhagic events occur in a significant fraction of acute promyelocytic
      leukemia patients, either at presentation and/or early after starting therapy,
      leading to treatment failure and early deaths. However, identification of
      independent predictors for high-risk of severe bleeding at diagnosis, remains a
      challenge. Here, we investigated the immunophenotype of bone marrow leukemic
      cells from 109 newly diagnosed acute promyelocytic leukemia patients,
      particularly focusing on the identification of basophil-related features, and
      their potential association with severe bleeding episodes and patient overall
      survival.From all phenotypes investigated on leukemic cells, expression of the
      CD203c and/or CD22 basophil-associated markers showed the strongest association
      with the occurrence and severity of bleeding (p <= 0.007); moreover, aberrant
      expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more
      frequently found among patients with (mild and severe) bleeding at baseline
      and/or after starting treatment (p <= 0.009). Multivariate analysis showed that
      CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio:
      5.4; p = 0.03) were the best independent predictors for cumulative incidence of
      severe bleeding after starting therapy. In addition, CD203c expression on
      leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard
      ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high
      leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative
      independent predictors for overall survival.In summary, our results show that the
      presence of basophil-associated phenotypic characteristics on leukemic cells from
      acute promyelocytic leukemia patients at diagnosis is a powerful independent
      predictor for severe bleeding and overall survival, which might contribute in the
      future to (early) risk-adapted therapy decisions.

PMID- 29572501
TI  - Array-based DNA-methylation profiling in sarcomas with small blue round cell
      histology provides valuable diagnostic information.
AB  - Undifferentiated solid tumors with small blue round cell histology and expression
      of CD99 mostly resemble Ewing sarcoma. However, they also may include other
      tumors such as mesenchymal chondrosarcoma, synovial sarcoma, or small cell
      osteosarcoma. Definitive classification usually requires detection of entity
      specific mutations. While this approach identifies the majority of Ewing
      sarcomas, a subset of lesions remains unclassified and, therefore, has been
      termed "Ewing-like sarcomas" or small blue round cell tumors not otherwise
      specified. We developed an approach for further characterization of small blue
      round cell tumors not otherwise specified using an array-based DNA-methylation
      profiling approach. Data were analyzed by unsupervised clustering and t
      distributed stochastic neighbor embedding analysis and compared with a reference
      methylation data set of 460 well-characterized prototypical sarcomas encompassing
      18 subtypes. Verification was performed by additional FISH analyses, RNA
      sequencing from formalin-fixed paraffin-embedded material or immunohistochemical
      marker analyses. In a cohort of more than 1,000 tumors assumed to represent Ewing
      sarcomas, 30 failed to exhibit the typical EWS translocation. These tumors were
      subjected to methylation profiling and could be assigned to Ewing sarcoma in 14
      (47%), to small blue round cell tumors with CIC alteration in 6 (20%), to small
      blue round cell tumors with BCOR alteration in 4 (13%), to synovial sarcoma and
      to malignant rhabdoid tumor in 2 cases each. One single case each was allotted to
      mesenchymal chondrosarcoma and adamantinoma. 12/14 tumors classified as Ewing
      sarcoma could be verified by demonstrating either a canonical EWS translocation
      evading initial testing, by identifying rare breakpoints or fusion partners. The
      methylation-based assignment of the remaining small blue round cell tumors not
      otherwise specified also could be verified by entity-specific molecular
      alterations in 13/16 cases. In conclusion, array-based DNA-methylation analysis
      of undifferentiated tumors with small blue round cell histology is a powerful
      tool for precisely classifying this diagnostically challenging tumor group.

PMID- 29572502
TI  - Interpretation of biological experiments changes with evolution of the Gene
      Ontology and its annotations.
AB  - Gene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high
      throughput molecular data and generating hypotheses about underlying biological
      phenomena of experiments. However, the two building blocks of this analysis - the
      ontology and the annotations - evolve rapidly. We used gene signatures derived
      from 104 disease analyses to systematically evaluate how enrichment analysis
      results were affected by evolution of the GO over a decade. We found low
      consistency between enrichment analyses results obtained with early and more
      recent GO versions. Furthermore, there continues to be a strong annotation bias
      in the GO annotations where 58% of the annotations are for 16% of the human
      genes. Our analysis suggests that GO evolution may have affected the
      interpretation and possibly reproducibility of experiments over time. Hence,
      researchers must exercise caution when interpreting GO enrichment analyses and
      should reexamine previous analyses with the most recent GO version.

PMID- 29572504
TI  - Timing of the Saalian- and Elsterian glacial cycles and the implications for
      Middle - Pleistocene hominin presence in central Europe.
AB  - By establishing a luminescence-based chronology for fluvial deposits preserved
      between the Elsterian- and Saalian tills in central Germany, we obtained
      information on the timing of both the Middle Pleistocene glacial cycles and early
      human appearance in central Europe. The luminescence ages illustrate different
      climatic driven fluvial aggradation periods during the Saalian glacial cycle
      spanning from 400-150 ka. The ages of sediments directly overlying the Elsterian
      till are approximately 400 ka and prove that the first extensive Fennoscandian
      ice sheet extension during the Quaternary correlates with MIS 12 and not with MIS
      10. Furthermore, the 400 ka old fluvial units contain Lower Paleolithic stone
      artefacts that document the first human appearance in the region. In addition, we
      demonstrate that early MIS 8 is a potential date for the onset of the Middle
      Paleolithic in central Germany, as Middle Paleolithic stone artefacts are
      correlated with fluvial units deposited between 300 ka and 200 ka. However, the
      bulk of Middle Paleolithic sites date to MIS 7 in the region. The fluvial units
      preserved directly under the till of the southernmost Saalian ice yield an age of
      about 150 ka, and enable a correlation of the Drenthe stage to late MIS 6.

PMID- 29572503
TI  - A genomics approach reveals insights into the importance of gene losses for
      mammalian adaptations.
AB  - Identifying the genomic changes that underlie phenotypic adaptations is a key
      challenge in evolutionary biology and genomics. Loss of protein-coding genes is
      one type of genomic change with the potential to affect phenotypic evolution.
      Here, we develop a genomics approach to accurately detect gene losses and
      investigate their importance for adaptive evolution in mammals. We discover a
      number of gene losses that likely contributed to morphological, physiological,
      and metabolic adaptations in aquatic and flying mammals. These gene losses shed
      light on possible molecular and cellular mechanisms that underlie these adaptive
      phenotypes. In addition, we show that gene loss events that occur as a
      consequence of relaxed selection following adaptation provide novel insights into
      species' biology. Our results suggest that gene loss is an evolutionary mechanism
      for adaptation that may be more widespread than previously anticipated. Hence,
      investigating gene losses has great potential to reveal the genomic basis
      underlying macroevolutionary changes.

PMID- 29572505
TI  - Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously
      treated mantle cell lymphoma from the phase 3, international, randomized, open
      label RAY study.

PMID- 29572506
TI  - Health-related quality of life in lower-risk MDS patients compared with age- and
      sex-matched reference populations: a European LeukemiaNet study.
AB  - In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL)
      represents a relevant patient-reported outcome, which is essential in
      individualized therapy planning. Prospective data on HRQoL in lower-risk MDS
      remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in
      1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet
      Registry. Impairments were compared with age- and sex-matched EuroQol Group
      norms. A significant proportion of MDS patients reported moderate/severe problems
      in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression
      (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual
      activities, pain/discomfort, and EQ-VAS were significantly more frequent in the
      old, in females, and in those with high co-morbidity burden, low haemoglobin
      levels, or red blood cells transfusion need (p < 0.001). In comparison to age-
      and sex-matched peers, the proportion of problems in usual activities and
      anxiety/depression was significantly higher in MDS patients (p < 0.001). MDS
      related restrictions in the dimension mobility were most prominent in males, and
      in older people (p < 0.001); in anxiety/depression in females and in younger
      people (p < 0.001); and in EQ-VAS in women and in persons older than 75 years (p
      < 0.05). Patients newly diagnosed with IPSS lower-risk MDS experience a
      pronounced reduction in HRQoL and a clustering of restrictions in distinct
      dimensions of HRQoL as compared with reference populations.

PMID- 29572507
TI  - Nucleolin promotes execution of the hematopoietic stem cell gene expression
      program.

PMID- 29572508
TI  - Structural basis of DUX4/IGH-driven transactivation.
AB  - Oncogenic fusions are major drivers in leukemogenesis and may serve as potent
      targets for treatment. DUX4/IGHs have been shown to trigger the abnormal
      expression of ERGalt through binding to DUX4-Responsive-Element (DRE), which
      leads to B-cell differentiation arrest and a full-fledged B-ALL. Here, we
      determined the crystal structures of Apo- and DNADRE-bound DUX4HD2 and revealed a
      clamp-like transactivation mechanism via the double homeobox domain. Biophysical
      characterization showed that mutations in the interacting interfaces
      significantly impaired the DNA binding affinity of DUX4 homeobox. These
      mutations, when introduced into DUX4/IGH, abrogated its transactivation activity
      in Reh cells. More importantly, the structure-based mutants significantly
      impaired the inhibitory effects of DUX4/IGH upon B-cell differentiation in mouse
      progenitor cells. All these results help to define a key DUX4/IGH-DRE
      recognition/step in B-ALL.

PMID- 29572509
TI  - In-vivo biomagnetic characterisation of the American cockroach.
AB  - We present a quantitative method, utilising a highly sensitive quantum sensor,
      that extends applicability of magnetorelaxometry to biological samples at
      physiological temperature. The observed magnetic fields allow for non-invasive
      determination of physical properties of magnetic materials and their surrounding
      environment inside the specimen. The method is applied to American cockroaches
      and reveals magnetic deposits with strikingly different behaviour in alive and
      dead insects. We discuss consequences of this finding to cockroach magneto
      reception. To our knowledge, this work represents the first characterisation of
      the magnetisation dynamics in live insects and helps to connect results from
      behavioural experiments on insects in magnetic fields with characterisation of
      magnetic materials in their corpses.

PMID- 29572510
TI  - Same habitat types but different use: evidence of context-dependent habitat
      selection in roe deer across populations.
AB  - With the surge of GPS-technology, many studies uncovered space use of mobile
      animals and shed light on the underlying behavioral mechanisms of habitat
      selection. Habitat selection and variation in either occurrence or strength of
      functional responses (i.e. how selection changes with availability) have given
      new insight into such mechanisms within populations in different ecosystems.
      However, linking variation in habitat selection to site-specific conditions in
      different populations facing contrasting environmental conditions but the same
      habitat type has not yet been investigated. We aimed to fill this knowledge gap
      by comparing within-home range habitat selection across 61 female roe deer
      (Capreolus capreolus) during the most critical life history stage in three study
      areas showing the same habitat types but with different environmental conditions.
      Female roe deer markedly differed in habitat selection within their home range,
      both within and among populations. Females facing poor environmental conditions
      clearly displayed a functional response, whereas females facing rich
      environmental conditions did not show any functional response. These results
      demonstrate how the use of a given habitat relative to its availability strongly
      varies in response to environmental conditions. Our findings highlight that the
      same habitat composition can lead to very different habitat selection processes
      across contrasted environments.

PMID- 29572511
TI  - Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome
      resembling accelerated aging.
AB  - Chronic obstructive pulmonary disease (COPD) has been recently characterized as a
      disease of accelerated lung aging, but the mechanism remains unclear.
      Tetraspanins have emerged as key players in malignancy and inflammatory diseases.
      Here, we found that CD9/CD81 double knockout (DKO) mice with a COPD-like
      phenotype progressively developed a syndrome resembling human aging, including
      cataracts, hair loss, and atrophy of various organs, including thymus, muscle,
      and testis, resulting in shorter survival than wild-type (WT) mice. Consistent
      with this, DNA microarray analysis of DKO mouse lungs revealed differential
      expression of genes involved in cell death, inflammation, and the sirtuin-1
      (SIRT1) pathway. Accordingly, expression of SIRT1 was reduced in DKO mouse lungs.
      Importantly, siRNA knockdown of CD9 and CD81 in lung epithelial cells additively
      decreased SIRT1 and Foxo3a expression, but reciprocally upregulated the
      expression of p21 and p53, leading to reduced cell proliferation and elevated
      apoptosis. Furthermore, deletion of these tetraspanins increased the expression
      of pro-inflammatory genes and IL-8. Hence, CD9 and CD81 might coordinately
      prevent senescence and inflammation, partly by maintaining SIRT1 expression.
      Altogether, CD9/CD81 DKO mice represent a novel model for both COPD and
      accelerated senescence.

PMID- 29572512
TI  - Cultured bloodstream Trypanosoma brucei adapt to life without mitochondrial
      translation release factor 1.
AB  - Trypanosoma brucei is an extracellular parasite that alternates between an insect
      vector (procyclic form) and the bloodstream of a mammalian host (bloodstream
      form). While it was previously reported that mitochondrial release factor 1
      (TbMrf1) is essential in cultured procyclic form cells, we demonstrate here that
      in vitro bloodstream form cells can tolerate the elimination of TbMrf1.
      Therefore, we explored if this discrepancy is due to the unique bioenergetics of
      the parasite since procyclic form cells rely on oxidative phosphorylation;
      whereas bloodstream form cells utilize glycolysis for ATP production and FoF1
      ATPase to maintain the essential mitochondrial membrane potential. The observed
      disruption of intact bloodstream form FoF1-ATPases serves as a proxy to indicate
      that the translation of its mitochondrially encoded subunit A6 is impaired
      without TbMrf1. While these null mutants have a decreased mitochondrial membrane
      potential, they have adapted by increasing their dependence on the electrogenic
      contributions of the ADP/ATP carrier to maintain the mitochondrial membrane
      potential above the minimum threshold required for T. brucei viability in vitro.
      However, this inefficient compensatory mechanism results in avirulent mutants in
      mice. Finally, the depletion of the codon-independent release factor TbPth4 in
      the TbMrf1 knockouts further exacerbates the characterized mitchondrial
      phenotypes.

PMID- 29572513
TI  - Hybrid graphene/cadmium-free ZnSe/ZnS quantum dots phototransistors for UV
      detection.
AB  - Graphene-based optoelectronic devices have attracted much attention due to their
      broadband photon responsivity and fast response time. However, the performance of
      such graphene-based photodetectors is greatly limited by weak light absorption
      and low responsivity induced by the gapless nature of graphene. Here, we achieved
      a high responsivity above 103 AW-1 for Ultraviolet (UV) light in a hybrid
      structure based phototransistor, which consists of CVD-grown monolayer graphene
      and ZnSe/ZnS core/shell quantum dots. The photodetectors exhibit a selective
      photo responsivity for the UV light with the wavelength of 405 nm, confirming the
      main light absorption from QDs. The photo-generated charges have been found to
      transfer from QDs to graphene channel, leading to a gate-tunable photo
      responsivity with the maximum value obtained at V G about 15V. A recirculate 100
      times behavior with a good stability of 21 days is demonstrated for our devices
      and another flexible graphene/QDs based photoconductors have been found to be
      functional after 1000 bending cycles. Such UV photodetectors based on graphene
      decorated with cadmium-free ZnSe/ZnS quantum dots offer a new way to build
      environmental friendly optoelectronics.

PMID- 29572514
TI  - Magnetic domain interactions of Fe3O4 nanoparticles embedded in a SiO2 matrix.
AB  - Currently, superparamagnetic functionalized systems of magnetite (Fe3O4)
      nanoparticles (NPs) are promising options for applications in hyperthermia
      therapy, drug delivery and diagnosis. Fe3O4 NPs below 20 nm have stable single
      domains (SSD), which can be oriented by magnetic field application. Dispersion of
      Fe3O4 NPs in silicon dioxide (SiO2) matrix allows local SSD response with
      uniaxial anisotropy and orientation to easy axis, 90 degrees  <001> or 180
      degrees  <111>. A successful, easy methodology to produce Fe3O4 NPs (6-17 nm) has
      been used with the Stober modification. NPs were embedded in amorphous and
      biocompatible SiO2 matrix by mechanical stirring in citrate and tetraethyl
      orthosilicate (TEOS). Fe3O4 NPs dispersion was sampled in the range of 2-12 h to
      observe the SiO2 matrix formation as time function. TEM characterization
      identified optimal conditions at 4 h stirring for separation of SSD Fe3O4 in SiO2
      matrix. Low magnetization (Ms) of 0.001 emu and a coercivity (Hc) of 24.75 Oe
      indicate that the embedded SSD Fe3O4 in amorphous SiO2 reduces the Ms by a
      diamagnetic barrier. Magnetic force microscopy (MFM) showed SSD Fe3O4 of 1.2 nm
      on average embedded in SiO2 matrix with uniaxial anisotropy response according to
      Fe3+ and Fe2+ electron spin coupling and rotation by intrinsic Neel contribution.

PMID- 29572515
TI  - Neuronal differentiation induces SNORD115 expression and is accompanied by post
      transcriptional changes of serotonin receptor 2c mRNA.
AB  - The serotonin neurotransmitter system is widespread in the brain and implicated
      in modulation of neuronal responses to other neurotransmitters. Among 14
      serotonin receptor subtypes, 5-HT2cR plays a pivotal role in controlling neuronal
      network excitability. Serotonergic activity conveyed through receptor 5-HT2cR is
      regulated post-transcriptionally via two mechanisms, alternative splicing and A
      to-I RNA editing. Brain-specific small nucleolar RNA SNORD115 harbours a
      phylogenetically conserved 18-nucleotide antisense element with perfect
      complementarity to the region of 5ht2c primary transcript that undergoes post
      transcriptional changes. Previous 5ht2c minigene studies have implicated SNORD115
      in fine-tuning of both post-transcriptional events. We monitored post
      transcriptional changes of endogenous 5ht2c transcripts during neuronal
      differentiation. Both SNORD115 and 5ht2c were upregulated upon neuronal
      commitment. We detected increased 5ht2c alternative exon Vb inclusion already at
      the stage of neuronal progenitors, and more extensive A-to-I editing of non
      targeted sites A and B compared to adjacent adenosines at sites E, C and D
      throughout differentiation. As the extent of editing is known to positively
      correlate with exon Vb usage while it reduces receptor functionality, our data
      support the model where SNORD115 directly promotes alternative exon inclusion
      without the requirement for conversion of key adenosines to inosines, thereby
      favouring production of full-length receptor isoforms with higher potency.

PMID- 29572516
TI  - Time-dependent memory transformation along the hippocampal anterior-posterior
      axis.
AB  - With time, memories undergo a neural reorganization that is linked to a
      transformation of detailed, episodic into more semantic, gist-like memory.
      Traditionally, this reorganization is thought to involve a redistribution of
      memory from the hippocampus to neocortical areas. Here we report a time-dependent
      reorganization within the hippocampus, along its anterior-posterior axis, that is
      related to the transformation of detailed memories into gist-like
      representations. We show that mnemonic representations in the anterior
      hippocampus are highly distinct and that anterior hippocampal activity is
      associated with detailed memory but decreases over time. Posterior hippocampal
      representations, however, are more gist-like at a later retention interval, and
      do not decline over time. These findings indicate that, in addition to the well
      known systems consolidation from hippocampus to neocortex, there are changes
      within the hippocampus that are crucial for the temporal dynamics of memory.

PMID- 29572517
TI  - Effect of tropical forest disturbance on the competitive interactions within a
      diverse ant community.
AB  - Understanding how anthropogenic disturbance influences patterns of community
      composition and the reinforcing interactive processes that structure communities
      is important to mitigate threats to biodiversity. Competition is considered a
      primary reinforcing process, yet little is known concerning disturbance effects
      on competitive interaction networks. We examined how differences in ant community
      composition between undisturbed and disturbed Bornean rainforest, is potentially
      reflected by changes in competitive interactions over a food resource. Comparing
      10 primary forest sites to 10 in selectively-logged forest, we found higher genus
      richness and diversity in the primary forest, with 18.5% and 13.0% of genera
      endemic to primary and logged respectively. From 180 hours of filming bait cards,
      we assessed ant-ant interactions, finding that despite considered aggression over
      food sources, the majority of ant interactions were neutral. Proportion of
      competitive interactions at bait cards did not differ between forest type,
      however, the rate and per capita number of competitive interactions was
      significantly lower in logged forest. Furthermore, the majority of genera showed
      large changes in aggression-score with often inverse relationships to their
      occupancy rank. This provides evidence of a shuffled competitive network, and
      these unexpected changes in aggressive relationships could be considered a type
      of competitive network re-wiring after disturbance.

PMID- 29572518
TI  - The properties of fibreboard based on nanolignocelluloses/CaCO3/PMMA composite
      synthesized through mechano-chemical method.
AB  - The purpose of this study was to develop a rapid and green method for the
      synthesis of lignocelluloses-based materials with superior mechanical properties.
      Samples were produced by hot-pressed method using different concentrations of
      CaCO3 and poly (methyl methacrylate) particles-filled nanolignocelluloses
      composites which was synthesized through mechano-chemical method. Poly (methyl
      methacrylate) and CaCO3 nanoparticles have been used as nanofillers. Bending
      strength, elasticity modulus, and dimensional stability, thermal properties of
      the developed lignocelluloses-based composites were determined. In view of the
      experimental results, it is found that the composites materials have good
      mechanical, dimensional stability, and thermal properties which enhanced as the
      filler loading increased. Thus, herein described lignocelluloses-based materials
      showed important characteristics to be concluded that these composites are
      suitable to be used for the design of flooring and construction systems.

PMID- 29572519
TI  - Three-dimensional variations of the slab geometry correlate with earthquake
      distributions at the Cascadia subduction system.
AB  - Significant along-strike variations of seismicity are observed at subduction
      zones, which are strongly influenced by physical properties of the plate
      interface and rheology of the crust and mantle lithosphere. However, the role of
      the oceanic side of the plate boundary on seismicity is poorly understood due to
      the lack of offshore instrumentations. Here tomographic results of the Cascadia
      subduction system, resolved with full-wave ambient noise simulation and inversion
      by integrating dense offshore and onshore seismic datasets, show significant
      variations of the oceanic lithosphere along strike and down dip from spreading
      centers to subduction. In central Cascadia, where seismicity is sparse, the slab
      is imaged as a large-scale low-velocity feature near the trench, which is
      attributed to a highly hydrated and strained oceanic lithosphere underlain by a
      layer of melts or fluids. The strong correlation suggests that the properties of
      the incoming oceanic plate play a significant role on seismicity.

PMID- 29572520
TI  - Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of
      Ischemia and beta-Amyloid Toxicity.
AB  - Ischemic stroke and diabetes are vascular risk factors for the development of
      impaired memory such as dementia and/or Alzheimer's disease. Clinical studies
      have demonstrated that minor striatal ischemic lesions in combination with beta
      amyloid (Abeta) load are critical in generating cognitive deficits. These
      cognitive deficits are likely to be associated with impaired insulin signaling.
      In this study, we examined the histological presence of insulin-like growth
      factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct
      brain circuits compared with morphological brain damage in a co-morbid rat model
      of striatal ischemia (ET1) and Abeta toxicity. The results demonstrated a rapid
      increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Abeta + ET1
      rats, mainly in the ipsilateral striatum and distant regions with synaptic links
      to the striatal lesion. These regions included subcortical white matter, motor
      cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region
      and horizontal diagonal band of Broca in the basal forebrain. The alteration in
      IGF-1 and IRS-1 presence induced by ET1 or Abeta rats alone was not severe enough
      to affect the entire brain circuit. Understanding the causal or etiologic
      interaction between insulin and IGF signaling and co-morbidity after ischemia and
      Abeta toxicity will help design more effective therapeutics.

PMID- 29572521
TI  - Thermal management and non-reciprocal control of phonon flow via optomechanics.
AB  - Engineering phonon transport in physical systems is a subject of interest in the
      study of materials, and has a crucial role in controlling energy and heat
      transfer. Of particular interest are non-reciprocal phononic systems, which in
      direct analogy to electric diodes, provide a directional flow of energy. Here, we
      propose an engineered nanostructured material, in which tunable non-reciprocal
      phonon transport is achieved through optomechanical coupling. Our scheme relies
      on breaking time-reversal symmetry by a spatially varying laser drive, which
      manipulates low-energy acoustic phonons. Furthermore, we take advantage of
      developments in the manipulation of high-energy phonons through controlled
      scattering mechanisms, such as using alloys and introducing disorder. These
      combined approaches allow us to design an acoustic isolator and a thermal diode.
      Our proposed device will have potential impact in phonon-based information
      processing, and heat management in low temperatures.

PMID- 29572523
TI  - Language lessons.

PMID- 29572522
TI  - Non-invasive quantification of human swallowing using a simple motion tracking
      system.
AB  - The number of patients with dysphagia is rapidly increasing due to the ageing of
      the population. Therefore, the importance of objectively assessing swallowing
      function has received increasing attention. Videofluoroscopy and videoendoscopy
      are the standard clinical examinations for dysphagia, but these techniques are
      not suitable for daily use because of their invasiveness. Here, we aimed to
      develop a novel, non-invasive method for measuring swallowing function using a
      motion tracking system, the Kinect v2 sensor. Five males and five females with
      normal swallowing function participated in this study. We defined three mouth
      related parameters and two larynx-related parameters and recorded data from 2.5
      seconds before to 2.5 seconds after swallowing onset. Changes in mouth-related
      parameters were observed before swallowing and reached peak values at the time of
      swallowing. In contrast, larynx-related parameters showed little change before
      swallowing and reached peak values immediately after swallowing. This simple
      swallow tracking system (SSTS) successfully quantified the swallowing process
      from the oral phase to the laryngeal phase. This SSTS is non-invasive, wireless,
      easy to set up, and simultaneously measures the dynamics of swallowing from the
      mouth to the larynx. We propose the SSTS for use as a novel and non-invasive
      swallowing assessment tool in the clinic.

PMID- 29572524
TI  - Software support for environmental evidence synthesis.

PMID- 29572525
TI  - The balance between concepts and complexity in ecology.

PMID- 29572526
TI  - Rapid and lasting gains from solving illegal fishing.
AB  - Perhaps the greatest challenge facing global fisheries is that recovery often
      requires substantial short-term reductions in fishing effort, catches and
      profits. These costs can be onerous and are borne in the present; thus, many
      countries are unwilling to undertake such socially and politically unpopular
      actions. We argue that many nations can recover their fisheries while avoiding
      these short-term costs by sharply addressing illegal, unreported and unregulated
      (IUU) fishing. This can spur fishery recovery, often at little or no cost to
      local economies or food provision. Indonesia recently implemented aggressive
      policies to curtail the high levels of IUU fishing it experiences from foreign
      flagged vessels. We show that Indonesia's policies have reduced total fishing
      effort by at least 25%, illustrating with empirical evidence the possibility of
      achieving fishery reform without short-term losses to the local fishery economy.
      Compared with using typical management reforms that would require a 15% reduction
      in catch and 16% reduction in profit, the approach of curtailing IUU has the
      potential to generate a 14% increase in catch and a 12% increase in profit.
      Applying this model globally, we find that addressing IUU fishing could
      facilitate similar rapid, long-lasting fisheries gains in many regions of the
      world.

PMID- 29572527
TI  - Effects of high pressure on the electrical resistivity and dielectric properties
      of nanocrystalline SnO 2.
AB  - The electrical transport and structural properties of tin oxide nanoparticles
      under compression have been studied by in situ impedance measurements and
      synchrotron X-ray diffraction (XRD) up to 27.9 GPa. It was found that the
      conduction of SnO2 can be improved significantly with compression. Abnormal
      variations in resistivity, relaxation frequency, and relative permittivity were
      observed at approximately 12.3 and 25.0 GPa, which can be attributed to pressure
      induced tetragonal- orthorhombic-cubic structural transitions. The dielectric
      properties of the SnO2 nanoparticles were found to be a function of pressure, and
      the dielectric response was dependent on frequency and pressure. The dielectric
      constant and loss tangent decreased with increasing frequency. Relaxation-type
      dielectric behaviour dominated at low frequencies. Whereas, modulus spectra
      indicated that charge carrier short-range motion dominated at high frequencies.

PMID- 29572529
TI  - A cross-species judgement bias task: integrating active trial initiation into a
      spatial Go/No-go task.
AB  - Judgement bias tasks are promising tools to assess emotional valence in animals,
      however current designs are often time-consuming and lack aspects of validity.
      This study aimed to establish an improved design that addresses these issues and
      can be used across species. Horses, rats, and mice were trained on a spatial
      Go/No-go task where animals could initiate each trial. The location of an open
      goal-box, at either end of a row of five goal-boxes, signalled either reward
      (positive trial) or non-reward (negative trial). Animals first learned to
      approach the goal-box in positive trials (Go) and to re-initiate/not approach in
      negative trials (No-go). Animals were then tested for responses to ambiguous
      trials where goal-boxes at intermediate locations were opened. The Go:No-go
      response ratio was used as a measure of judgement bias. Most animals quickly
      learned the Go/No-go discrimination and performed trials at a high rate compared
      to previous studies. Subjects of all species reliably discriminated between
      reference cues and ambiguous cues, demonstrating a monotonic graded response
      across the different cue locations, with no evidence of learning about the
      outcome of ambiguous trials. This novel test protocol is an important step
      towards a practical task for comparative studies on judgement biases in animals.

PMID- 29572528
TI  - Cell-free protein synthesis from genomically recoded bacteria enables multisite
      incorporation of noncanonical amino acids.
AB  - Cell-free protein synthesis has emerged as a powerful approach for expanding the
      range of genetically encoded chemistry into proteins. Unfortunately, efforts to
      site-specifically incorporate multiple non-canonical amino acids into proteins
      using crude extract-based cell-free systems have been limited by release factor 1
      competition. Here we address this limitation by establishing a bacterial cell
      free protein synthesis platform based on genomically recoded Escherichia coli
      lacking release factor 1. This platform was developed by exploiting multiplex
      genome engineering to enhance extract performance by functionally inactivating
      negative effectors. Our most productive cell extracts enabled synthesis of 1,780
      +/- 30 mg/L superfolder green fluorescent protein. Using an optimized platform,
      we demonstrated the ability to introduce 40 identical p-acetyl-L-phenylalanine
      residues site specifically into an elastin-like polypeptide with high accuracy of
      incorporation ( >= 98%) and yield (96 +/- 3 mg/L). We expect this cell-free
      platform to facilitate fundamental understanding and enable manufacturing
      paradigms for proteins with new and diverse chemistries.

PMID- 29572530
TI  - Geographical variation of diabetic emergencies attended by prehospital Emergency
      Medical Services is associated with measures of ethnicity and socioeconomic
      status.
AB  - Geographical variation of diabetic emergencies attended by prehospital emergency
      medical services (EMS) and the relationship between area-level social and
      demographic factors and risk of a diabetic emergency were examined. All cases of
      hypoglycaemia and hyperglycaemia attended by Ambulance Victoria between 1/01/2009
      and 31/12/2015 were tabulated by Local Government Area (LGA). Conditional
      autoregressive models were used to create smoothed maps of age and gender
      standardised incidence ratio (SIR) of prehospital EMS attendance for a diabetic
      emergency. Spatial regression models were used to examine the relationship
      between risk of a diabetic emergency and area-level factors. The areas with the
      greatest risk of prehospital EMS attendance for a diabetic emergency were
      disperse. Area-level factors associated with risk of a prehospital EMS-attended
      diabetic emergency were socioeconomic status (SIR 0.70 95% CrI [0.51, 0.96]),
      proportion of overseas-born residents (SIR 2.02 95% CrI [1.37, 2.91]) and motor
      vehicle access (SIR 1.47 95% CrI [1.08, 1.99]). Recognition of areas of increased
      risk of prehospital EMS-attended diabetic emergencies may be used to assist
      prehospital EMS resource planning to meet increased need. In addition,
      identification of associated factors can be used to target preventative
      interventions tailored to individual regions to reduce demand.

PMID- 29572531
TI  - Cross-platform mass spectrometry annotation in breathomics of oesophageal-gastric
      cancer.
AB  - Disease breathomics is gaining importance nowadays due to its usefulness as non
      invasive early cancer detection. Mass spectrometry (MS) technique is often used
      for analysis of volatile organic compounds (VOCs) associated with cancer in the
      exhaled breath but a long-standing challenge is the uncertainty in mass peak
      annotation for potential volatile biomarkers. This work describes a cross
      platform MS strategy employing selected-ion flow tube mass spectrometry (SIFT
      MS), high resolution gas chromatography-mass spectrometry (GC-MS) retrofitted
      with electron ionisation (EI) and GC-MS retrofitted with positive chemical
      ionisation (PCI) as orthogonal analytical approaches in order to provide facile
      identification of the oxygenated VOCs from breath of cancer patients. In
      addition, water infusion was applied as novel efficient PCI reagent in
      breathomics analysis, depicting unique diagnostic ions M+ or [M-17]+ for VOC
      identification. Identity confirmation of breath VOCs was deduced using the
      proposed multi-platform workflow, which reveals variation in breath oxygenated
      VOC composition of oesophageal-gastric (OG) cancer patients with dominantly
      ketones, followed by aldehydes, alcohols, acids and phenols in decreasing order
      of relative abundance. Accurate VOC identification provided by cross-platform
      approach would be valuable for the refinement of diagnostic VOC models and the
      understanding of molecular drivers of VOC production.

PMID- 29572532
TI  - Electrocaloric effect in cubic Hubbard nanoclusters.
AB  - In the paper a computational study of the electrocaloric effect is presented for
      a cubic nanocluster consisting of 8 sites. The system of interest is described by
      means of an extended Hubbard model in external electric field at half filling of
      the energy levels. The thermodynamic description is obtained within canonical
      ensemble formalism on the basis of exact numerical diagonalization of the system
      Hamiltonian. In particular, the entropy and the specific heat are determined as a
      function of temperature and external electric field. The electrocaloric effect is
      described quantitatively by isothermal entropy change. The behaviour of this
      quantity is thoroughly analysed as a function of extended Hubbard model
      parameters, temperature and electric field variation magnitude. The existence of
      direct and inverse electrocaloric effect is predicted for some range of model
      parameters. A high sensitivity to Hubbard model parameters is shown, what paves
      the way towards controlling and tuning the effect. A non-linear, quadratic
      dependence of isothermal entropy change on electric field variation magnitude is
      demonstrated. The potential for applications of electrocaloric effect in strongly
      correlated nanoclusters is shown.

PMID- 29572533
TI  - Nature-Inspired Hierarchical Steels.
AB  - Materials can be made strong, but as such they are often brittle and prone to
      fracture when under stress. Inspired by the exceptionally strong and ductile
      structure of byssal threads found in certain mussels, we have designed and
      manufactured a multi-hierarchical steel, based on an inexpensive austenitic
      stainless steel, which defeats this "conflict" by possessing both superior
      strength and ductility. These excellent mechanical properties are realized by
      structurally introducing sandwich structures at both the macro- and nano-scales,
      the latter via an isometric, alternating, dual-phase crystal phases comprising
      nano-band austenite and nano-lamellar martensite, without change in chemical
      composition. Our experiments (transmission and scanning electron microscopy,
      electron back-scattered diffraction, nano-indentation and tensile tests) and
      micromechanics simulation results reveal a synergy of mechanisms underlying such
      exceptional properties. This synergy is key to the development of vastly superior
      mechanical properties, and may provide a unique strategy for the future
      development of new super strong and tough (damage-tolerant), lightweight and
      inexpensive structural materials.

PMID- 29572534
TI  - The effects of hydroxyethyl starch and gelatine on pulmonary cytokine production
      and oedema formation.
AB  - Recently, side effects of plasma expanders like hydroxyethyl starch and gelatine
      gained considerable attention. Most studies have focused on the kidneys; lungs
      remain unconsidered. Isolated mouse lungs were perfused for 4 hours with buffer
      solutions based on hydroxyethyl starch (HES) 130/0.4, HES 200/0.5 or gelatine and
      ventilated with low or high pressure under physiological pH and alkalosis.
      Outcome parameters were cytokine levels and the wet-to-dry ratio. For cytokine
      release, murine and human PCLS were incubated in three different buffers and time
      points.In lungs perfused with the gelatine based buffer IL-6, MIP-2 and KC
      increased when ventilated with high pressure. Wet-to-dry ratios increased
      stronger in lungs perfused with gelatine - compared to HES 130/0.4. Alkalotic
      perfusion resulted in higher cytokine levels but normal wet-to-dry ratio. Murine
      PCLS supernatants showed increased IL-6 and KC when incubated in gelatine based
      buffer, whereas in human PCLS IL-8 was elevated. In murine IPL HES 130/0.4 has
      lung protective effects in comparison to gelatine based infusion solutions,
      especially in the presence of high-pressure ventilation. Gelatine perfusion
      resulted in increased cytokine production. Our findings suggest that gelatine
      based solutions may have side effects in patients with lung injury or lung
      oedema.

PMID- 29572535
TI  - Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients
      according to their outcomes.
AB  - Assessing the phenotypic diversity underlying tumour progression requires the
      identification of variations in the respective molecular interaction networks.
      Here we report proof-of-concept for a platform called poly-ligand profiling (PLP)
      that surveys these system states and distinguishes breast cancer patients who did
      or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast
      cancer specimens to enrich single-stranded DNA (ssDNA) libraries that
      preferentially interact with molecular components associated with the two
      clinical phenotypes. Testing of independent sample sets verifies the ability of
      PLP to classify trastuzumab-treated patients according to their clinical outcomes
      with ROC-AUC of 0.78. Standard HER2 testing of the same patients gives a ROC-AUC
      of 0.47. Kaplan-Meier analysis reveals a median increase in benefit from
      trastuzumab-containing treatments of 300 days for PLP-positive compared to PLP
      negative patients. If prospectively validated, PLP may increase success rates in
      precision oncology and clinical trials, thus improving both patient care and drug
      development.

PMID- 29572536
TI  - Dual role of YM1+ M2 macrophages in allergic lung inflammation.
AB  - Alternatively activated (M2 or YM1+) macrophages have been associated with the
      development of asthma but their contribution to disease initiation and
      progression remains unclear. To assess the therapeutic potential of modulating
      these M2 macrophages, we have studied inhibition of M2 polarisation during and
      after development of allergic lung inflammation by treating with cynaropicrin, a
      galectin-3 pathway inhibitor. Mice that were treated with this inhibitor of M2
      polarisation during induction of allergic inflammation developed less severe
      eosinophilic lung inflammation and less collagen deposition around airways, while
      the airway alpha-smooth muscle actin layer was unaffected. When we treated with
      cynaropicrin after induction of inflammation, eosinophilic lung inflammation and
      collagen deposition were also inhibited though to a lesser extent. Unexpectedly,
      both during and after induction of allergic inflammation, inhibition of M2
      polarisation resulted in a shift towards neutrophilic inflammation. Moreover,
      airway hyperresponsiveness was worse in mice treated with cynaropicrin as
      compared to allergic mice without inhibitor. These results show that M2
      macrophages are associated with remodeling and development of eosinophilic lung
      inflammation, but prevent development of neutrophilic lung inflammation and
      worsening of airway hyperresponsiveness. This study suggests that macrophages
      contribute to determining development of eosinophilic or neutrophilic lung
      inflammation in asthma.

PMID- 29572537
TI  - Intralayer and interlayer electron-phonon interactions in twisted graphene
      heterostructures.
AB  - The understanding of interactions between electrons and phonons in atomically
      thin heterostructures is crucial for the engineering of novel two-dimensional
      devices. Electron-phonon (el-ph) interactions in layered materials can occur
      involving electrons in the same layer or in different layers. Here we report on
      the possibility of distinguishing intralayer and interlayer el-ph interactions in
      samples of twisted bilayer graphene and of probing the intralayer process in
      graphene/h-BN by using Raman spectroscopy. In the intralayer process, the el-ph
      scattering occurs in a single graphene layer and the other layer (graphene or h
      BN) imposes a periodic potential that backscatters the excited electron, whereas
      for the interlayer process the el-ph scattering occurs between states in the
      Dirac cones of adjacent graphene layers. Our methodology of using Raman
      spectroscopy to probe different types of el-ph interactions can be extended to
      study any kind of graphene-based heterostructure.

PMID- 29572538
TI  - In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc
      receptor.
AB  - Lowering the total level of Immunoglobulin G (IgG) in circulation is a promising
      general treatment option for many autoimmune diseases driven by pathogenic
      autoantibodies. The half-life of IgG in circulation is unusually long as a
      consequence of its interaction with the neonatal Fc receptor (FcRn), which
      protects it from lysosomal degradation by cells in contact with blood. Blocking
      the IgG/FcRn interaction prevents FcRn-mediated rescue, which may lead to
      increased catabolism and a lowering of the total IgG level. Here, we find that an
      engineered alternative scaffold protein, an affibody molecule, interacting
      specifically with FcRn, is able to block the IgG/FcRn interaction in vitro. The
      affibody molecule (ZFcRn) was expressed alone or as a fusion to an albumin
      binding domain (ABD), to extend its half-life in circulation, in both cases with
      retained affinity and blocking potential. Repeated i.v. injections in mice of
      ZFcRn and ZFcRn-ABD were found to result in an up to 40% reduction of the IgG
      serum-level after 5 days. Potential applications of ZFcRn as a general treatment
      modality for autoimmune diseases are discussed.

PMID- 29572539
TI  - Methodology challenges in studying human gut microbiota - effects of collection,
      storage, DNA extraction and next generation sequencing technologies.
AB  - The information on microbiota composition in the human gastrointestinal tract
      predominantly originates from the analyses of human faeces by application of next
      generation sequencing (NGS). However, the detected composition of the faecal
      bacterial community can be affected by various factors including experimental
      design and procedures. This study evaluated the performance of different
      protocols for collection and storage of faecal samples (native and OMNIgene.GUT
      system) and bacterial DNA extraction (MP Biomedicals, QIAGEN and MO BIO kits),
      using two NGS platforms for 16S rRNA gene sequencing (Ilumina MiSeq and Ion
      Torrent PGM). OMNIgene.GUT proved as a reliable and convenient system for
      collection and storage of faecal samples although favouring Sutterella genus. MP
      provided superior DNA yield and quality, MO BIO depleted Gram positive organisms
      while using QIAGEN with OMNIgene.GUT resulted in greatest variability compared to
      other two kits. MiSeq and IT platforms in their supplier recommended setups
      provided comparable reproducibility of donor faecal microbiota. The differences
      included higher diversity observed with MiSeq and increased capacity of MiSeq to
      detect Akkermansia muciniphila, [Odoribacteraceae], Erysipelotrichaceae and
      Ruminococcaceae (primarily Faecalibacterium prausnitzii). The results of our
      study could assist the investigators using NGS technologies to make informed
      decisions on appropriate tools for their experimental pipelines.

PMID- 29572540
TI  - Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the
      mTOR pathway in TNF-alpha mediated inflammatory conditions: an in-vitro study.
AB  - Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment
      modality for fracture healing, however, the mechanism of their action remains
      unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast
      proliferation and differentiation. This study aimed to assess the osteogenic
      differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the
      potential involvement of mTOR signaling pathway in this process. PEMFs were
      generated by a novel miniaturized electromagnetic device. Potential changes in
      the expression of mTOR pathway components, including receptors, ligands and
      nuclear target genes, and their correlation with osteogenic markers and
      transcription factors were analyzed. Involvement of the mTOR pathway in
      osteogenesis was also studied in the presence of proinflammatory mediators. PEMF
      exposure increased cell proliferation and adhesion and the osteogenic commitment
      of MSCs even in inflammatory conditions. Osteogenic-related genes were over
      expressed following PEMF treatment. Our results confirm that PEMFs contribute to
      activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase,
      and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF
      stimulated osteogenic differentiation. Our findings provide insights into how
      PEMFs influence osteogenic differentiation in normal and inflammatory
      environments.

PMID- 29572541
TI  - Dimer Interface of the Human Serotonin Transporter and Effect of the Membrane
      Composition.
AB  - The oligomeric state of membrane proteins has recently emerged in many cases as
      having an effect on their function. However, the intrinsic dynamics of their
      spatial organization in cells and model systems makes it challenging to
      characterize. Here we use molecular dynamics (MD) simulations at multiple
      resolutions to determine the dimer conformation of the human serotonin
      transporter (hSERT). From self-assembly simulations we predict dimer candidates
      and subsequently quantify their relative strength. We use umbrella sampling (US)
      replica exchange MD simulations for which we present extensive analysis of their
      efficiency and improved sampling compared to regular US MD simulations. The data
      shows that the most stable hSERT dimer interface is symmetrical and involves
      transmembrane helix 12 (TM12), similar to the crystal structure of the bacterial
      homologue LeuT, but with a slightly different orientation. We also describe the
      supramolecular organization of hSERT from a 250 MUs self-assembly simulation.
      Finally, the effects of the presence of phosphatidylinositol bisphosphate or
      cholesterol in the membrane model has been quantified for the TM12-TM12 predicted
      interface. Collectively, the presented data bring new insight to the area of
      protein and lipid interplay in biological membranes.

PMID- 29572542
TI  - Aryl hydrocarbon receptor signaling promotes ORMDL3-dependent generation of
      sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase.
AB  - Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular
      homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of
      sphingolipid metabolism, is believed to have a role in immunity and inflammation,
      but their potential crosstalk is currently unknown. We aimed to determine whether
      there is a functional linkage between AhR signaling and sphingolipid metabolism.
      We showed that AhR ligands, including an environmental polycyclic aromatic
      hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL)
      activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs
      exposed to the AhR ligand alone or in combination with antigen challenge. The
      reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue
      317, which was reversible by the addition of an antioxidant or in cells with
      knockdown of the ORMDL3 gene encoding an ER transmembrane protein, whereas C317A
      S1PL mutant-transfected cells were resistant to the AhR-mediated effect.
      Furthermore, analysis of AhR ligand-treated cells showed a time-dependent
      increase of the ORMDL3-S1PL complex, which was confirmed by FRET analysis. This
      change increased the S1P levels, which in turn, induced mast cell degranulation
      via S1PR2 signaling. In addition, elevated levels of plasma S1P were found in
      children with asthma compared to non-asthmatic subjects. These results suggest a
      new regulatory pathway whereby the AhR-ligand axis induces ORMDL3-dependent S1P
      generation by inhibiting S1PL, which may contribute to the expression of allergic
      diseases.

PMID- 29572544
TI  - High-throughput sequencing reveals similar molecular signatures for class switch
      recombination junctions for the gamma and alpha isotypes.

PMID- 29572543
TI  - The role of natural killer cells in the uterine microenvironment during
      pregnancy.

PMID- 29572545
TI  - NETosis, complement, and coagulation: a triangular relationship.
AB  - NETosis is a regulated form of neutrophil cell death that contributes to the host
      defense against pathogens and was linked to various diseases soon after its first
      description in 2004. During NETosis, neutrophils release neutrophil extracellular
      traps (NETs), which can capture and kill bacteria and other pathogens to prevent
      them from spreading. Although substantial progress has been made in our
      understanding of NETosis, the precise mechanism underlying NETosis is still a
      matter of debate. Research continues to elucidate the molecular pathways involved
      in NETosis. In recent years, interactions with the complement and coagulation
      systems have become increasingly apparent. Activated complement proteins can
      stimulate NET formation, and NETs, in turn, can serve as a platform for
      complement activation. In addition, NETs can act as a scaffold for thrombus
      formation during coagulation. While crosstalk between the coagulation and
      complement systems has been previously described, NETosis appears to be a third
      important player in this consortium to protect the host against pathogens. This
      review summarizes our current knowledge on the mutual interactions between
      NETosis, the complement system and the coagulation system, with an emerging
      description of their complex triangular relationship.

PMID- 29572546
TI  - The role of CD6 in autoimmune diseases.

PMID- 29572547
TI  - Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response
      and promotes epithelial cell proliferation.
AB  - The intracellular pathogen Mycobacterium tuberculosis (Mtb) can survive in the
      host and cause disease by interfering with a variety of cellular functions. The
      mammalian cell entry 2 (mce2) operon of Mtb has been shown to contribute to
      tuberculosis pathogenicity. However, little is known about the regulatory roles
      of Mtb Mce2 family proteins towards host cellular functions. Here we show that
      the Mce2 family protein Mce2E suppressed the macrophage innate immune response
      and promoted epithelial cell proliferation. Mce2E inhibited activation of the
      extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK)
      mitogen-activated protein kinase (MAPK) signaling pathways in a non-canonical D
      motif (a MAPK-docking motif)-dependent manner, leading to reduced expression of
      TNF and IL-6 in macrophages. Furthermore, Mce2E promoted proliferation of human
      lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked
      polyubiquitination of eEF1A1 in a beta strand region-dependent manner. In
      summary, Mce2E is a novel multifunctional Mtb virulence factor that regulates
      host cellular functions in a niche-dependent manner. Our data suggest a potential
      novel target for TB therapy.

PMID- 29572548
TI  - T cells from induced and spontaneous models of SLE recognize a common T cell
      epitope on beta2-glycoprotein I.
AB  - Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in
      autoimmunity. Autoantibodies to numerous molecularly distinct self-antigens
      emerge in a sequential manner over several years, leading to disease
      manifestations. Among the earliest autoantibodies to appear are those targeting
      phospholipid-binding proteins, particularly beta2-glycoprotein I. Notably, mice
      immunized with beta2-glycoprotein I and lipopolysaccharide develop a strong T
      cell response to beta2-glycoprotein I that is associated with autoantibody
      production and renal disease, similar to that seen in human SLE. Here we
      hypothesized that mice with murine systemic lupus erythematosus, whether induced
      or spontaneous, should have T cells that recognize beta2-glycoprotein I. We
      evaluated the response of splenic T cells from mice with induced (C57BL/6 and
      C3H/HeN) and spontaneous (MRL/lpr) systemic lupus erythematosus to peptides
      spanning the entire sequence of human beta2GPI. We found that mice with induced
      and spontaneous systemic lupus erythematosus recognize a common T cell epitope
      (peptide 31; LYRDTAVFECLPQHAMFG) in domain III of beta2-glycoprotein I. beta2GPI
      reactive CD4+ T cells from the two models differed primarily in cytokine
      production: T cells from mice with induced SLE expressed IFN-gamma, while T cells
      from MRL/lpr mice expressed both IL-17 and IFN-gamma, indicating that IL-17
      expressing T cells are not necessary for generating a beta2GPI-reactive T cell
      response. These data suggest that the generation of a beta2-glycoprotein I
      reactive T cell response is shared by both induced and spontaneous models of
      systemic lupus erythematosus and that this T cell response may mediate epitope
      spread to autoantibodies in both models.

PMID- 29572549
TI  - Mechanistic insights into cancer immunity and immunotherapy.

PMID- 29572550
TI  - Delayed allogeneic skin graft rejection in CD26-deficient mice.
AB  - Organ transplantation is an effective therapeutic tool for treating many terminal
      diseases. However, one of the biggest challenges of transplantation is
      determining how to achieve the long-term survival of the allogeneic or xenogeneic
      transplant by, for example, preventing transplant rejection. In the current
      study, CD26 gene-knockout mice were used to investigate the potential role of
      CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail
      skin transplantation. Compared with wild-type (CD26+/+) counterparts, CD26-/-
      mice showed reduced necrosis of grafts and delayed graft rejection after skin
      transplantation. Concentrations of serum IgG, including its subclasses IgG1 and
      IgG2a, were significantly reduced in CD26-/- mice during graft rejection.
      Moreover, after allogeneic skin transplantation, the secretion levels of the
      cytokines IFN-gamma, IL-2, IL-6, IL-4, and IL-13 were significantly reduced,
      whereas the level of the cytokine IL-10 was increased in the serum of CD26-/-
      mice compared with that in the serum of CD26+/+ mice. Additionally, the
      concentration of IL-17 in serum and the percentage of cells secreting IL-17 in
      mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while
      the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of
      CD26-/- mice than in those of CD26+/+ mice. Furthermore, a lower percentage of
      CD8+ T cells in MPBLs and fewer infiltrated macrophages and T cells in graft
      tissues of CD26-/- mice were detected during graft rejection. These results
      indicate that CD26 is involved in allogeneic skin graft rejection and provides
      another hint that CD26 deficiency leads to less rejection due to lower activation
      and proliferation of host immune cells.

PMID- 29572551
TI  - Lack of evidence supporting a role of TMC4-rs641738 missense variant-MBOAT7-
      intergenic downstream variant-in the Susceptibility to Nonalcoholic Fatty Liver
      Disease.
AB  - Current knowledge on the genetic basis of nonalcoholic fatty liver disease
      (NAFLD) suggests that variants contributing not only to the disease
      predisposition but histological severity as well are located in genes that
      regulate lipid metabolism. We explored the role of rs641738 C/T located in TMC4
      (transmembrane channel-like 4) exon 1 (p.Gly17Glu) and 500 bases- downstream of
      MBOAT7 gene (TMC4/MBOAT7), in the genetic risk for developing NAFLD in a case
      control study. Our sample included 634 individuals (372 patients with NAFLD
      diagnosed by liver biopsy and 262 control subjects); genotyping was performed by
      a Taqman assay. Genotype frequencies in controls (CC: 84, CT: 137, TT: 41) and
      patients (CC: 134, CT: 178, TT: 60) were in Hardy-Weinberg equilibrium; minor
      allele frequency 40.8%. Our sample had 84-99% power if an additive genetic model
      is assumed for estimated odds ratios of 1.3-1.5, respectively. We found no
      evidence of association between rs641738 and either NAFLD (Cochran-Armitage test
      for trend, p = 0.529) or the disease severity (p = 0.61). Low levels of MBOAT7
      protein expression were found in the liver of patients with NAFLD, which were
      unrelated to the rs641738 genotypes. In conclusion, the role of rs641738 in the
      pathogenesis of NAFLD is inconclusive.

PMID- 29572552
TI  - Dietary carbohydrates: a review of international recommendations and the methods
      used to derive them.
AB  - BACKGROUND/OBJECTIVES: Renewed dietary recommendations for carbohydrates have
      recently been published by various international health authorities. The present
      work (1) reviews the methods and processes (systematic approach/review, inclusion
      of public consultation) used to identify, select and grade the evidence
      underpinning the recommendations, particularly for total carbohydrate (CHO),
      fibre and sugar consumption, and (2) examines the extent to which variation in
      the methods and processes applied relates to any differences in the final
      recommendations. SUBJECTS/METHODS: A search of WHO, US, Canada, Australia and
      European sources identified 19 documents from 13 authorities with the desired
      detailed information. Processes and methods applied to derive recommendations
      were compiled and compared. RESULTS: (1) A relatively high total CHO and fibre
      intake and limited intake of (added or free) sugars are generally recommended.
      (2) Even where recommendations are similar, the specific justifications for
      quantitative/qualitative recommendations differ across authorities. (3)
      Differences in recommendations mainly arise from differences in the underlying
      definitions of CHO exposure and classifications, the degree to which specific CHO
      providing foods and food components were considered, and the choice and number of
      health outcomes selected. (4) Differences in the selection of source material,
      time frames or data aggregation and grading methods appeared to have minor
      influence. CONCLUSIONS: Despite general consistency, apparent differences among
      the recommendations of different authorities would likely be minimized by: (1)
      More explicit quantitative justifications for numerical recommendations and
      communication of uncertainty, and (2) greater international harmonization,
      particularly in the underlying definitions of exposures and range of relevant
      nutrition-related outcomes.

PMID- 29572553
TI  - Galantamine anti-colitic effect: Role of alpha-7 nicotinic acetylcholine receptor
      in modulating Jak/STAT3, NF-kappaB/HMGB1/RAGE and p-AKT/Bcl-2 pathways.
AB  - Vagal stimulation controls systemic inflammation and modulates the immune
      response in different inflammatory conditions, including inflammatory bowel
      diseases (IBD). The released acetylcholine binds to alpha-7 nicotinic
      acetylcholine receptor (alpha7 nAChR) to suppress pro-inflammatory cytokines.
      This provides a new range of potential therapeutic approaches for controlling
      inflammatory responses. The present study aimed to assess whether galantamine
      (Galan) anti-inflammatory action involves alpha7 nAChR in a 2,4,6-trinitrobenzene
      sulfonic acid (TNBS) model of colitis and to estimate its possible molecular
      pathways. Rats were assigned into normal, TNBS, sulfasalazine (Sulfz), Galan
      treated (10 mg/kg), methyllycaconitine (MLA; 5.6 mg/kg), and MLA + Galan groups.
      Drugs were administered orally once per day (11 days) and colitis was induced on
      the 8th day. Galan reduced the TNBS-induced ulceration, colon mass index, colonic
      MDA, neutrophils adhesion and infiltration (ICAM-1/MPO), inflammatory mediators
      (NF-kappaB, TNF-alpha, HMGB1, and RAGE), while increased the anti-apoptotic
      pathway (p-Akt/Bcl-2). Mechanistic study revealed that Galan increased the anti
      inflammatory cytokine IL-10, phosphorylated Jak2, while reduced the inflammation
      controller SOCS3. However, combining MLA with Galan abrogated the beneficial anti
      inflammatory/anti-apoptotic signals. The results of the present study indicate
      that Galan anti-inflammatory/-apoptotic/ -oxidant effects originate from the
      stimulation of the peripheral alpha7 nAChR, with the involvement of the
      Jak2/SOCS3 signaling pathway.

PMID- 29572554
TI  - MultiBacMam Bimolecular Fluorescence Complementation (BiFC) tool-kit identifies
      new small-molecule inhibitors of the CDK5-p25 protein-protein interaction (PPI).
AB  - Protein-protein interactions (PPIs) are at the core of virtually all biological
      processes in cells. Consequently, targeting PPIs is emerging at the forefront of
      drug discovery. Cellular assays which closely recapitulate native conditions in
      vivo are instrumental to understand how small molecule drugs can modulate such
      interactions. We have integrated MultiBacMam, a baculovirus-based mammalian gene
      delivery tool we developed, with bimolecular fluorescence complementation (BiFC),
      giving rise to a highly efficient system for assay development, identification
      and characterization of PPI modulators. We used our system to analyze compounds
      impacting on CDK5-p25 PPI, which is implicated in numerous diseases including
      Alzheimer's. We evaluated our tool-kit with the known inhibitor p5T, and we
      established a mini-screen to identify compounds that modulate this PPI in dose
      response experiments. Finally, we discovered several compounds disrupting CDK5
      p25 PPI, which had not been identified by other screening or structure-based
      methods before.

PMID- 29572555
TI  - Ameliorating Effects of Leaf Water Extract of Three Aromatic Plant Species on
      Ozone-Polluted Snap Bean (Phaseolus vulgaris L. 'Jiangjunyoudou').
AB  - Ozone (O3) is one of the major pollutants in near-surface air. In order to
      protect sensitive plants from O3 pollution, many kinds of protectants including
      synthetic ones, were assessed in previous studies. Although they have certain
      protective effects, some of them are not environment-friendly. In the present
      study, leaf water extracts of aromatic plants [Plectranthus hadiensis var.
      tomentosus (PHT), Pelargonium hortorum (PHB), Tagetes patula (TP)] were compared
      for mitigating the damages caused by O3 (150 ppb for 3 days, 8 h day-1) on snap
      bean (Phaseolus vulgaris 'Jiangjunyoudou'). Our results showed that O3 fumigation
      impaired plasma membrane, decreased chlorophyll content, increased contents of
      malondialdehyde and superoxide anion, inhibited photosynthesis, and caused
      visible injury. Leaf water extracts of PHT, PHB or TP ameliorated the negative
      effects of O3. Among them, extract of PHT showed the greatest potential to
      alleviate the O3-caused injury, followed by PHB and TP.

PMID- 29572556
TI  - Good clinical and functional outcomes at mid-term following autologous
      osteochondral transplantation for osteochondral lesions of the talus.
AB  - PURPOSE: Autologous osteochondral transplantation is an established treatment for
      large-sized osteochondral lesions of the talus (OLT) with excellent short term
      outcomes. However, few studies assess the outcomes of autologous osteochondral
      transplantation at mid-term follow-up. The purpose of the current systematic
      review was to evaluate the clinical outcomes of the autologous osteochondral
      transplantation procedure in the treatment of OLT at mid-term and long-term
      follow-up. METHODS: A systematic search of the MEDLINE, EMBASE and Cochrane
      Library databases was performed in October 2017 based on the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included
      studies were evaluated with regard to level of evidence (LOE) and quality of
      evidence (QOE) using the Coleman Methodology Score. Clinical outcomes, and
      complications were also evaluated. RESULTS: Eleven studies, with 500 ankles were
      included at a mean 62.8 months follow-up. Seven studies used the American
      Orthopaedic Foot and Ankle Society (AOFAS) score. The weighted mean preoperative
      AOFAS score was 55.1 +/- 6.1, and the postoperative score was 86.2 +/- 4.5, with
      87.4% of patients (132 of 151) being reported as excellent or good results. In
      total, 53 of the 500 patients (10.6%) had complications. The most common
      complication was donor site morbidity with 18 patients (3.6%) at final follow-up.
      Thirty-one patients (6.2%) underwent reoperations, and 5 ankles (1.0%) were
      regarded as failed autologous osteochondral transplantation. CONCLUSION: The
      current systematic review demonstrated that good clinical and functional outcomes
      can be expected following autologous osteochondral transplantation for the
      treatment of OLT, with a low failure rate. The results from this study show
      patients can be reasonably counselled to expect good clinical outcomes in the mid
      term. MRI and radiographs showed restoration of articular surface as well as a
      minimal presence of osteoarthritis at mid-term follow-up. However, as low level
      and quality of evidence and the variability of the data may confound the data,
      further well-designed studies are necessary to determine the effectiveness of
      autologous osteochondral transplantation in the treatment for OLT. LEVEL OF
      EVIDENCE: IV.

PMID- 29572557
TI  - ?

PMID- 29572559
TI  - An Integrative Review of Empirical Research on Perceptions and Behaviors Related
      to Prescribed Burning and Wildfire in the United States.
AB  - Social science research from a variety of disciplines has generated a collective
      understanding of how individuals prepare for, and respond to, the risks
      associated with prescribed burning and wildfire. We provide a systematic
      compilation, review, and quantification of dominant trends in this literature by
      collecting all empirical research conducted within the U.S. that has addressed
      perceptions and behaviors surrounding various aspects of prescribed burning and
      wildfire. We reviewed and quantified this literature using four thematic
      categories covering: (1) the theory and methods that have been used in previous
      research; (2) the psychosocial aspects of prescribed burning and wildfire that
      have been studied; (3) the biophysical characteristics of the fires which have
      been studied; and (4) the types of fire and management approaches that have been
      examined. Our integrative review builds on previous literature reviews on the
      subject by offering new insight on the dominant trends, underutilized approaches,
      and under-studied topics within each thematic category. For example, we found
      that a select set of theories (e.g., Protection Motivation Theory, Attribution
      Theory, etc.) and approaches (e.g., mixed-methods) have only been used sparingly
      in previous research, even though these theories and approaches can produce
      insightful results that can readily be implemented by fire-management
      professionals and decision makers. By identifying trends and gaps in the
      literature across the thematic categories, we were able to answer four questions
      that address how future research can make the greatest contribution to our
      understanding of perceptions and behaviors related to prescribed burning and
      wildfire.

PMID- 29572558
TI  - Modulation of sodium channels as pharmacological tool for pain therapy-highlights
      and gaps.
AB  - Voltage-gated sodium channels are crucially involved in the transduction and
      transmission of nociceptive signals and pathological pain states. In the past
      decades, a lot of effort has been spent examining and characterizing biophysical
      properties of the different sodium channels and their role in signaling pathways.
      Several gains of function mutations of the sodium channels Nav1.7, Nav1.8, and
      Nav1.9 are associated with pain disorders. Due to their critical role in
      nociceptive pathways voltage-gated sodium channels are regarded interesting
      targets for pharmacological pain treatment. However we still need to fill the gap
      that exists in the translation of efficacy in preclinical in vitro experiments
      and in models of pain into the clinic. This review summarizes biological and
      electrophysiological properties of voltage-gated sodium channels and aims to
      discuss limitations and promising pharmacological strategies in sodium channel
      research in the context of pain therapy.

PMID- 29572560
TI  - Cell permeability and nuclear DNA staining by propidium iodide in basidiomycetous
      yeasts.
AB  - Non-model yeasts within basidiomycetes have considerable importance in
      agriculture, industry, and environment, but they are not as well studied as
      ascomycetous yeasts. Serving as a basic technique, nuclear DNA staining is widely
      used in physiology, ecology, cell biology, and genetics. However, it is unclear
      whether the classical nuclear DNA staining method for ascomycetous yeasts is
      applicable to basidiomycetous yeasts. In this study, 5 yeasts ineffectively
      stained by the classical propidium iodide (PI) staining method were identified
      from 23 representative basidiomycetous yeasts. Pretreatment of cells using
      dimethyl sulfoxide (DMSO) or snailase markedly improved cell penetration to PI
      and thus enabled DNA content determination by flow cytometry on the recalcitrant
      yeasts. The pretreatments are efficient, simple, and fast, avoiding tedious
      mutagenesis or genetic engineering used in previous reports. The heterogeneity of
      cell penetration to PI among basidiomycetous yeasts was attributed to the
      discrepancy in cell wall polysaccharides instead of capsule or plasma membrane.
      This study also indicated that care must be taken in attributing PI-negative
      staining as viable cells when studying non-model microorganisms.

PMID- 29572562
TI  - Autosomal Recessive Osteogenesis Imperfecta Caused by a Novel Homozygous COL1A2
      Mutation.
AB  - Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle
      bones and extraskeletal manifestations. The disease phenotype varies greatly.
      Most commonly, OI arises from monoallelic mutations in one of the two genes
      encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal
      dominant trait. Here, we describe a consanguineous family with autosomal
      recessive OI caused by a novel homozygous glycine substitution in COL1A2,
      NM_000089.3: c.604G>A, p.(Gly202Ser), detected by whole-genome sequencing. The
      index patient is a 31-year-old Greek woman with severe skeletal fragility. She
      had mild short stature, low bone mineral density of the lumbar spine and blue
      sclerae. She had sustained multiple long bone and vertebral fractures since
      childhood and had been treated with bisphosphonates for several years. She also
      had an affected sister with similar clinical manifestations. Interestingly, the
      parents and one sister, all carriers of the COL1A2 glycine mutation, did not have
      manifestations of OI. In summary, we report on autosomal recessive OI caused by a
      homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal
      fragility. The mutation carriers lacked OI manifestations. This family further
      expands the complex genetic spectrum of OI and underscores the importance of
      genetic evaluation for correct genetic counselling.

PMID- 29572561
TI  - Autoimmune disorders are common in myelodysplastic syndrome patients and confer
      an adverse impact on outcomes.
AB  - The coexistence of autoimmune disorders (AD) in patients with myelodysplastic
      syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely
      recognized, although with distinct results regarding their prevalence and impact
      on the outcomes of the underlying hematological process. This study was aimed to
      analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in
      a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both
      the presence of clinical symptoms or compatible serological tests. In total, 48%
      patients were diagnosed as having AD, being hypothyroidism the most commonly
      reported clinical AD (8%) and antinuclear antibodies the most frequent
      serological parameter identified (23.2%). The presence of AD was associated with
      female gender, lower hemoglobin levels, and higher IPSS-R. Overall survival for
      patients with AD was inferior to those with no AD (69 vs. 88% at 30 months; HR
      2.75, P = 0.008). Notably, clinical but not isolated immune serological
      parameters had an impact on the outcomes of patients with AD. Finally, in a
      multivariate analysis, the presence of AD (HR 2.26) along with disease risk
      categories (very low and low vs. intermediate, high, and very high IPSS-R; HR
      4.62) retained their independent prognostic value (P < 0.001). In conclusion, AD
      are prevalent in MDS and CMML patients and have prognostic implications,
      especially in lower-risk MDS patients.

PMID- 29572564
TI  - Letter to the Editor: Enhanced Recovery After Surgery for Low- and Middle-Income
      Countries.

PMID- 29572563
TI  - Assessment of inter-racial variability in CYP3A4 activity and inducibility among
      healthy adult males of Caucasian and South Asian ancestries.
AB  - PURPOSE: Cytochrome P450 (CYP) 3A4 is responsible for the metabolism of more than
      30% of clinically used drugs. Inherent between subject variability in clearance
      of CYP3A4 substrates is substantial; by way of example, midazolam clearance
      varies by > 10-fold between individuals before considering the impact of
      extrinsic factors. Relatively little is known about inter-racial variability in
      the activity of this enzyme. METHODS: This study assessed inter-racial
      variability in midazolam exposure in a cohort (n = 30) of CYP3A genotyped, age
      matched healthy males of Caucasian and South Asian ancestries. Midazolam exposure
      was assessed at baseline, following 7 days of rifampicin and following 3 days of
      clarithromycin. RESULTS: The geometric mean baseline midazolam area under the
      plasma concentration curve (AUC0-6) in Caucasians (1057 MUg/L/min) was 27%
      greater than South Asians (768 MUg/L/min). Similarly, the post-induction
      midazolam AUC0-6 in Caucasians (308 MUg/L/min) was 50% greater than South Asians
      (154 MUg/L/min), while the post-inhibition midazolam AUC0-6 in Caucasians (1834
      MUg/L/min) was 41% greater than South Asians (1079 MUg/L/min). The difference in
      baseline AUC0-6 between Caucasians and South Asians was statistically significant
      (p <= 0.05), and a trend toward significance (p = 0.067) was observed for the
      post-induction AUC0-6 ratio, in both unadjusted and genotype adjusted analyses.
      CONCLUSIONS: Significantly higher midazolam clearance was observed in healthy age
      matched males of South Asian compared to Caucasian ancestry that was not
      explained by differences in the frequency of CYP3A genotypes.

PMID- 29572565
TI  - Hospital Teaching Status and Patients' Outcomes After Colon Cancer Surgery.
AB  - BACKGROUND AND OBJECTIVES: It is increasingly accepted that quality of colon
      cancer surgery might be secured by combining volume standards with audit
      implementation. However, debate remains about other structural factors also
      influencing this quality, such as hospital teaching status. This study evaluates
      short-term outcomes after colon cancer surgery of patients treated in general,
      teaching or academic hospitals. METHODS: All patients (n = 23,593) registered in
      the Dutch Colorectal Audit undergoing colon cancer surgery between 2011 and 2014
      were included. Patients were divided into groups based on teaching status of
      their hospital. Main outcome measures were serious complications, failure to
      rescue (FTR) and 30-day or in-hospital mortality. Multivariate logistic
      regression models on these outcome measures and with hospital teaching status as
      primary determinant were used, adjusted for case-mix, year of surgery and
      hospital volume. RESULTS: Patients treated in teaching and academic hospitals
      showed higher adjusted serious complication rates, compared to patients treated
      in general hospitals (odds ratio 1.25 95% CI [1.11-1.39] and OR 1.23 [1.05
      1.46]). However, patients treated in teaching hospitals had lower adjusted FTR
      rates than patients treated in general hospitals (OR 0.63 [0.44-0.89]). However,
      for all outcomes there was considerable between-hospitals variation within each
      type of teaching status. CONCLUSION: On average, patients treated in general
      hospitals had lower serious complication rates, but patients treated in teaching
      hospitals had more favorable FTR rates. Given the hospital variation within each
      hospital teaching type, it is possible to deliver excellent care regardless of
      the hospital teaching type.

PMID- 29572566
TI  - Functional characterization of Kv11.1 (hERG) potassium channels split in the
      voltage-sensing domain.
AB  - Voltage-dependent KCNH family potassium channel functionality can be
      reconstructed using non-covalently linked voltage-sensing domain (VSD) and pore
      modules (split channels). However, the necessity of a covalent continuity for
      channel function has not been evaluated at other points within the two
      functionally independent channel modules. We find here that by cutting Kv11.1
      (hERG, KCNH2) channels at the different loops linking the transmembrane spans of
      the channel core, not only channels split at the S4-S5 linker level, but also
      those split at the intracellular S2-S3 and the extracellular S3-S4 loops, yield
      fully functional channel proteins. Our data indicate that albeit less markedly,
      channels split after residue 482 in the S2-S3 linker resemble the uncoupled
      gating phenotype of those split at the C-terminal end of the VSD S4 transmembrane
      segment. Channels split after residues 514 and 518 in the S3-S4 linker show
      gating characteristics similar to those of the continuous wild-type channel.
      However, breaking the covalent link at this level strongly accelerates the
      voltage-dependent accessibility of a membrane impermeable methanethiosulfonate
      reagent to an engineered cysteine at the N-terminal region of the S4
      transmembrane helix. Thus, besides that of the S4-S5 linker, structural integrity
      of the intracellular S2-S3 linker seems to constitute an important factor for
      proper transduction of VSD rearrangements to opening and closing the cytoplasmic
      gate. Furthermore, our data suggest that the short and probably rigid
      characteristics of the extracellular S3-S4 linker are not an essential component
      of the Kv11.1 voltage sensing machinery.

PMID- 29572568
TI  - A 2-year follow-up MRI study for the evaluation of an age estimation method based
      on knee bone development.
AB  - Age estimation is an actual topic in the area of forensic medicine with a special
      focus on the age limits of 16 and 18 years. Current research on this topic relies
      on retrospective data of inhomogeneous populations relating to sex, age range,
      and socioeconomic status. In this work, we present a 2-year follow-up study for
      the evaluation of an age estimation method on a prospective magnetic resonance
      imaging (MRI) knee data collective of a homogeneous population. The study
      includes 40 male subjects from northern Germany aged 14 to 21 years. Three MRI
      examinations were evenly acquired within 2 years for each subject. As a first
      evaluation, a three-stage system was used to assess the ossification status of
      the knee (I:"open", II:"partially ossified", III:"fully ossified"). Three raters
      assessed the growth plate of the distal femur, proximal tibia, and proximal
      fibula based on central 2D slices. A good inter-rater agreement was attained
      (kappa = 0.84). All subjects younger than 18 years were rated as stage I and had
      a cumulative knee score (SKJ) <= 5. Based on the follow-up datasets, new
      parameters quantifying the intra-individual ossification process were calculated.
      The results of this follow-up analysis show a different start, end, and speed of
      each growth plate's maturation as well as an ossification peak for individuals at
      the age of 16. The generated MRI database provides new insights into the
      ossification process over time and serves as a basis for further evaluations of
      age estimation methods.

PMID- 29572567
TI  - Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising
      alternative.
AB  - Trichomonas vaginalis is an extracellular parasite that binds to the epithelium
      of the human urogenital tract and causes the sexually transmitted infection,
      trichomoniasis. In view of increased resistance to drugs belonging to the 5
      nitroimidazole class, new treatment alternatives are urgently needed. In this
      study, eight semisynthetized triterpene derivatives were evaluated for in vitro
      anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28
      oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared
      to other derivatives, with minimum inhibitory concentration (MIC) at 25 MUM.
      Moreover, 9 was active against several T. vaginalis fresh clinical isolates.
      Hemolysis assay demonstrated that 9 presented a low hemolytic effect.
      Importantly, 25 MUM 9 was not cytotoxic against the Vero cell lineage. Finally,
      we demonstrated that compound 9 acts synergistically with metronidazole against a
      T. vaginalis metronidazole-resistant isolate. This report reveals the high
      potential of the triterpenoid derivative 9 as trichomonicidal agent.

PMID- 29572569
TI  - The unprecedented 2014 Legionnaires' disease outbreak in Portugal: atmospheric
      driving mechanisms.
AB  - A large outbreak of Legionnaires' disease occurred in November 2014 nearby
      Lisbon, Portugal. This epidemic infected 377 individuals by the Legionella
      pneumophila bacteria, resulting in 14 deaths. The primary source of transmission
      was contaminated aerosolized water which, when inhaled, lead to atypical
      pneumonia. The unseasonably warm temperatures during October 2014 may have played
      a role in the proliferation of Legionella species in cooling tower systems. The
      episode was further exacerbated by high relative humidity and a thermal inversion
      which limited the bacterial dispersion. Here, we analyze if the Legionella
      outbreak event occurred during a situation of extreme potential recirculation
      and/or stagnation characteristics. In order to achieve this goal, the Allwine and
      Whiteman approach was applied for a hindcast simulation covering the affected
      area during a near 20-year long period (1989-2007) and then for an independent
      period covering the 2014 event (15 October to 13 November 2014). The results
      regarding the average daily critical transport indices for the 1989-2007 period
      clearly indicate that the airshed is prone to stagnation as these events have a
      dominant presence through most of the study period (42%), relatively to the
      occurrence of recirculation (18%) and ventilation (17%) events. However, the year
      of 2014 represents an exceptional year when compared to the 1989-2007 period,
      with 53 and 33% of the days being classified as under stagnation and
      recirculation conditions, respectively.

PMID- 29572570
TI  - Hemi-seesaw nystagmus in a patient with acute infarction in the superior
      cerebellar artery territory.

PMID- 29572571
TI  - Exploring the relationship between motor impairment, vascular burden and
      cognition in Parkinson's disease.
AB  - OBJECTIVE: To determine frequency and type of cognitive disorders in cross
      sectional analysis of a Parkinson's disease (PD) cohort, and explore its
      relations to motor symptoms, modifiable vascular risk factors and white matter
      lesions (WML) volume. METHODS: In a group of 133 PD patients, mild cognitive
      impairment (PD-MCI) and dementia (PDD) were diagnosed according to Movement
      Disorders Society Task Force criteria (level 2 for PD-MCI). Detailed motor
      measurements were applied, including rigidity, axial, bradykinesia, tremor and
      postural instability gait disorders (PIGD) scores. Vascular risk was estimated by
      the Framingham General Cardiovascular Disease risk scoring algorithm and WML
      volume was measured for whole brain and frontal lobe. RESULTS: Sixty-one (46.9%)
      patients fulfilled criteria for PD-MCI, and 23 (17.7%) for PDD. Non-amnestic
      multiple domain MCI was most frequent (52% of PD-MCI patients). Motor scores were
      significantly higher in cognitively impaired patients, but only axial score
      discriminated between MCI and dementia. High vascular risk was related to
      impaired cognition, bradykinesia, axial, PIGD and freezing of gait (FOG) score,
      while whole brain WML volume was associated with PDD, FOG and attention deficits.
      Furthermore, high vascular risk was identified as a potential predictor of both
      MCI and dementia in PD. Additionally, age and bradykinesia score were
      independently associated with PD-MCI and age, axial score and whole brain WML
      volume with PDD. CONCLUSION: Cognitive disorders in PD are associated with more
      severe, predominantly axial motor deficits and increased, but partly modifiable
      vascular burden, thus opening a possibility for development of preventive
      strategies in PD.

PMID- 29572572
TI  - Osseointegration mechanisms: a proteomic approach.
AB  - The prime objectives in the development of biomaterials for dental applications
      are to improve the quality of osseointegration and to short the time needed to
      achieve it. Design of implants nowadays involves changes in the surface
      characteristics to obtain a good cellular response. Incorporating osteoinductive
      elements is one way to achieve the best regeneration possible post-implantation.
      This study examined the osteointegrative potential of two distinct biomaterials:
      sandblasted acid-etched titanium and a silica sol-gel hybrid coating, 70% MTMOS
      30% TEOS. In vitro, in vivo, and proteomic characterisations of the two materials
      were conducted. Enhanced expression levels of ALP and IL-6 in the MC3T3-E1 cells
      cultured with coated discs, suggest that growing cells on such surfaces may
      increase mineralisation levels. 70M30T-coated implants showed improved bone
      growth in vivo compared to uncoated titanium. Complete osseointegration was
      achieved on both. However, coated implants displayed osteoinductive properties,
      while uncoated implants demonstrated osteoconductive characteristics. Coagulation
      related proteins attached predominantly to SAE-Ti surface. Surface properties of
      the material might drive the regenerative process of the affected tissue.
      Analysis of the proteins on the coated dental implant showed that few proteins
      specifically attached to its surface, possibly indicating that its osteoinductive
      properties depend on the silicon delivery from the implant.

PMID- 29572574
TI  - Polymorphism at donkey beta-lactoglobulin II locus: identification and
      characterization of a new genetic variant with a very low expression.
AB  - In the last years, donkey milk had evidenced a renewed interest as a potential
      functional food and a breast milk substitute. In this light, the study of the
      protein composition assumes an important role. In particular, beta-lactoglobulin
      (beta-LG), which is considered as one of the main allergenic milk protein, in
      donkey species consists of two molecular forms, namely beta-LG I and beta-LG II.
      In the present research, a genetic analysis coupled with a proteomic approach
      showed the presence of a new allele, here named F, which is apparently associated
      with a null or a severely reduced expression of beta-LG II protein. The new beta
      LG II F genetic variant shows a theoretical average mass (Mav) of 18,310.64 Da, a
      value practically corresponding with that of the variant D (?mass < 0.07 Da), but
      differs from beta-LG II D for two amino acid substitutions: Thr100 (variant F) ->
      Ala100 (variant D) and Thr118 (variant F) -> Met118 (variant D). Proteomic
      investigation of the whey protein fraction of an individual milk sample,
      homozygous FF at beta-LG II locus, allowed to identify, as very minor component,
      the new beta-LG II F genetic variant. By MS/MS analysis of enzymatic digests, the
      sequence of the beta-LG II F was characterized, and the predicted genomic data
      confirmed.

PMID- 29572573
TI  - Longitudinal Evaluation of Swallowing with Videofluoroscopy in Patients with
      Locally Advanced Head and Neck Cancer After Chemoradiation.
AB  - The aim of this study was to investigate the prevalence, severity, and pattern of
      evolution of swallowing impairments encountered in head and neck cancer (HNC)
      patients before and after chemoradiation (CRT) with videofluoroscopy of
      swallowing study (VFSS), using the modified barium swallow impairment profile
      (MBSImP) protocol and scoring system, and to determine the appropriate time
      points in which these patients should undergo VFSS post-CRT. A prospective cohort
      of 69 patients with locally advanced HNC underwent VFSS with the MBSImP protocol
      at 5 evaluation points: pre-CRT, and 1, 3, 6, and 12 months post-CRT. VFSS was
      scored with MBSImP, penetration-aspiration scale (PAS), and swallowing
      performance status (SPS) scale. Statistical analysis was performed only for the
      12-month disease-free subset of patients. MBSImP, PAS, and SPS scale scores
      reached their peak at 3 months post-CRT and improved at 6-12 months, but without
      returning at pre-treatment levels. Base of tongue retraction, initiation of
      pharyngeal swallow, epiglottic movement, laryngeal vestibule closure, and
      laryngeal elevation were the most frequently observed impaired MBSImP components.
      Epiglottic movement significantly improved (p = 0.009) and laryngeal vestibule
      closure significantly deteriorated (p = 0.042) over time (Friedman test). Severe
      swallowing deficits and high aspiration rates are observed in HNC patients pre
      CRT, which further deteriorate post-CRT, peak at 3 months, and despite slight
      improvement, persist over time. We suggest that these patients, regardless of the
      presence of subjective dysphagia, should undergo VFSS both before and 3 months
      post-CRT, and also if possible, 1 month post-CRT, in order to facilitate
      implementation of early swallowing rehabilitation.

PMID- 29572575
TI  - Metastatic colonic and gastric polyps from breast cancer resembling hyperplastic
      polyps.
AB  - Breast cancer metastasis to the gastrointestinal tract is relatively rare and is
      generally found when patients complain of symptoms such as gastrointestinal
      obstruction. Herein, we report a case with metastatic colonic and gastric lesions
      from breast cancer, with the formation of mucosal polyps which resembled typical
      hyperplastic polyps.A 47-year-old woman underwent curable surgery for breast
      cancer and received standard systemic treatments. Her primary tumor was composed
      of a mix of invasive lobular and ductal carcinomas. During adjuvant endocrine
      therapy, she developed multiple colonic metastases, identified by colonoscopy
      performed as part of a general health check-up. She had no symptoms. Small
      elevated sessile polyps in the transverse colon and rectum showed histological
      features of signet-ring cell type adenocarcinoma, similar to the invasive lobular
      component of the primary breast cancer. During treatments for recurrent disease,
      she also developed multiple gastric metastases, with the same endoscopic and
      pathological features as the colonic lesions. Her treatment regimen was switched
      to oral chemotherapy, and she has since maintained stable disease for nearly 3
      years. Multiple bone metastases eventually developed, and she was again switched
      to another systemic treatment but, to date, has remained free of symptoms.We
      emphasize that the endoscopic findings of the metastatic lesions in the colon and
      stomach in this case highly resembled hyperplastic polyps. Since biopsy is not
      always performed for hyperplastic polyps in the gastrointestinal tract, we
      believe that this case report may encourage endoscopists to offer biopsies to the
      patient who has a history of breast cancer.

PMID- 29572576
TI  - Integrated Behavioral Medicine in Cancer Care: Utilizing a Training Program Model
      to Provide Psychological Services in an Urban Cancer Center.
AB  - Psycho-oncology has come of age as its own unique subspecialty under the umbrella
      of oncology, vastly refining our knowledge regarding the psychosocial impact of
      cancer and fostering acceptance of the psychological underpinnings of the cancer
      experience, in turn improving the overall quality of cancer care. The importance
      of integrating psychological practice into the comprehensive treatment of cancer
      has become readily apparent, and psychosocial support services are increasing in
      quantity and breadth. It is the aim of this article to present a cogent argument
      for the proliferation of Integrated Behavioral Medicine (IBM) programs in both
      inpatient and outpatient clinical cancer treatment centers via an in-depth
      discussion of a successful IBM program including analysis of program structure,
      service delivery model and description of clinical services provided, and a
      longitudinal review of referral trends.

PMID- 29572577
TI  - Mechanisms of vision loss in eyes with macular edema associated with retinal vein
      occlusion.
AB  - Anti-vascular endothelial growth factor agents reduce macular edema and improve
      vision in eyes with macular edema associated with retinal vein occlusion (RVO),
      including branch RVO (BRVO) and central RVO. However, not all eyes with resolved
      macular edema show satisfactory best corrected visual acuity. Photoreceptor
      impairment can mostly explain the vision loss in these cases. Photoreceptor
      damage can be caused by subretinal hemorrhage in the central fovea and hard
      exudates or their precursor derived from concentrated lipoproteins originating
      from leaky retinal vessel extravasation. The contribution of neuron impairment in
      the inner retina, including the impairment of bipolar and ganglion cells by
      ischemia, indicated by the presence of a non-perfusion area (NPA), to vision loss
      in eyes with BRVO is insignificant. This is because the papillomacular bundle
      area is usually spared from NPAs in BRVO cases.

PMID- 29572578
TI  - Crucial role of P2X7 receptor for effector T cell activation in experimental
      autoimmune uveitis.
AB  - PURPOSE: To investigate the roles of P2X7 receptors (P2RX7) in the pathogenesis
      of experimental autoimmune uveoretinitis (EAU). STUDY DESIGN: Experimental.
      METHODS: Either wild-type (P2rx7 +/+ ) or P2rx7-deficient (P2rx7 -/- ) mice were
      immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-20.
      Severity of EAU was evaluated clinically and histopathologically. The induction
      of IRBP-specific proliferation and cytokines in draining lymph nodes was assessed
      by enzyme-linked immunosorbent assays (ELISA). The frequency of activation
      markers was examined by flow cytometry. Furthermore, inhibitory roles of systemic
      administration of Brilliant Blue G (BBG), an antagonist for P2RX7, in EAU were
      also assessed in the wild-type mice. RESULTS: The severity of EAU in P2rx7 -/-
      mice was reduced as compared with that in P2rx7 +/+ mice, both clinically and
      histopathologically. IRBP-specific proliferation in P2rx7 -/- on day 16 was
      slightly decreased compared to that in P2rx7 +/+ mice. The induction of IRBP
      specific interferon (IFN)-gamma and interleukin (IL)-17 in P2rx7 -/- mice on day
      16 was lower than that in P2rx7 +/+ mice. The up-regulation of surface expression
      of activation markers such as CD25, CD44, and CD69 in response to TCR stimulation
      in P2rx7 -/- mice was decreased as compared with that in P2rx7 +/+ mice.
      Furthermore, neutralization of P2RX7 in vivo by BBG suppressed EAU clinically and
      histopathologically. IRBP-specific IFN-gamma and IL-17 induction in BBG-treated
      mice was significantly lower than that in vehicle-treated mice. CONCLUSION: The
      results suggest that P2RX7 is a novel preventative therapeutic target for uveitis
      as it suppresses the effector functions of both Th1 and Th17 cell responses.

PMID- 29572579
TI  - Surgical management of giant intrapetrous internal carotid aneurysm presenting
      with coil exposure after endovascular treatment.
AB  - Giant intrapetrous internal carotid aneurysms (petrous ICA aneurysm) are rare. A
      giant petrous ICA aneurysm presenting with otorrhagia and coil exposure to the
      external auditory meatus (EAM) after endovascular treatment has never been
      documented before. The authors report here a case of successful surgical trapping
      with bypass intervention of a giant petrous ICA aneurysm presenting with coil
      exposure after endovascular treatment. A 58-year-old man presented with
      persistent otorrhagia having been admitted to our hospital because of the
      recurrence of a giant petrous ICA aneurysm after repeated embolization treatments
      with coils. An electronic otoscope examination demonstrated that a piece of coil
      escaped into his right EAM. After multidisciplinary consultation, an extracranial
      intracranial (EC-IC) bypass with ICA occlusion and coil removal with a closed EAM
      filling were performed in stages. The patient recovered quickly without any
      neurological deficits. A digital subtraction angiography confirmed the absence of
      the aneurysm and patency of the bypass graft.

PMID- 29572580
TI  - Mere ownership of memory: motor manipulation during encoding affects memory for
      words.
AB  - Involving the body in learning increases the impact information has on memory
      (Johnson-Glenberg et al. in Front Psychol 7(1819):1-22, 2016), especially when
      that information is self-relevant (Truong et al. in J Exp Psychol Hum Percept
      Perform 42(3):375-385, 2016). Yet, prior research has only examined the effect of
      self-relevant movement (i.e., toward the self or away from the self) on memory
      through passive joystick flexion or extension (Oakes and Onyper in Cognit Process
      18:325-333, 2017). Therefore, the current research sought to replicate the
      "toward: remember" and "away: forget" motor-induced self-reference effects on
      memory with actual body movement. Participants in two experiments took notes on a
      word list and either pushed notes away, pulled notes toward them, moved notes
      laterally, or wrote the words in a list. Results showed that participants who
      pulled hand-written notes toward them had better recall than those who pushed
      notes away from them or moved them laterally. Results suggest implicitly taking
      ownership of material in an embodied manner may influence how much is recalled.

PMID- 29572581
TI  - Marginal Zone Lymphoma: Clinicopathologic Variations and Approaches to Therapy.
AB  - PURPOSE OF REVIEW: The purpose of the study is to summarize the current
      conundrums in the management of marginal zone lymphomas (MZL). RECENT FINDINGS:
      In 2017, the US Food and Drug Administration (FDA) approved ibrutinib, a first in
      class Bruton Tyrosine Kinase inhibitor, for the treatment of relapsed/refractory
      MZL based on pivotal open-label phase II trial demonstrating an overall response
      rates of 48%. Clinical trials design utilizing chemotherapy-free regimens for
      relapsed/refractory disease are gaining popularity. Recent studies have
      identified multiple genetic biomarkers that helped characterize and prognosticate
      different subtypes of MZL. MZLs are heterogeneous, mostly indolent, malignancies
      derived from B lymphocytes. Three disease subtypes are recognized, extranodal,
      nodal, and splenic. The disease characteristics, clinical picture, and treatment
      algorithms vary considerably based on subtype and site of involvement. Recent
      discoveries have enhanced our knowledge of the pathogenesis of MZLs leading to
      development of more accurate prognostic models as well as novel targeted systemic
      therapies.

PMID- 29572583
TI  - Insights into the human oral microbiome.
AB  - Human oral cavity harbors the second most abundant microbiota after the
      gastrointestinal tract. The expanded Human Oral Microbiome Database (eHOMD) that
      was last updated on November 22, 2017, contains the information of approximately
      772 prokaryotic species, where 70% is cultivable, and 30% belong to the
      uncultivable class of microorganisms along with whole genome sequences of 482
      taxa. Out of 70% culturable species, 57% have already been assigned to their
      names. The 16S rDNA profiling of the healthy oral cavity categorized the
      inhabitant bacteria into six broad phyla, viz. Firmicutes, Actinobacteria,
      Proteobacteria, Fusobacteria, Bacteroidetes and Spirochaetes constituting 96% of
      total oral bacteria. These hidden oral micro-inhabitants exhibit a direct
      influence on human health, from host's metabolism to immune responses. Altered
      oral microflora has been observed in several diseases such as diabetes,
      bacteremia, endocarditis, cancer, autoimmune disease and preterm births.
      Therefore, it becomes crucial to understand the oral microbial diversity and how
      it fluctuates under diseased/perturbed conditions. Advances in metagenomics and
      next-generation sequencing techniques generate rapid sequences and provide
      extensive information of inhabitant microorganisms of a niche. Thus, the
      retrieved information can be utilized for developing microbiome-based biomarkers
      for their use in early diagnosis of oral and associated diseases. Besides,
      several apex companies have shown keen interest in oral microbiome for its
      diagnostic and therapeutic potential indicating a vast market opportunity. This
      review gives an insight of various associated aspects of the human oral
      microbiome.

PMID- 29572582
TI  - Systemic Treatment Options for Advanced-Stage Mycosis Fungoides and Sezary
      Syndrome.
AB  - PURPOSE OF REVIEW: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin
      lymphoma. Globally, the most common subtypes of CTCL are mycosis fungoides and
      Sezary syndrome. CTCL can confer significant morbidity and even mortality in
      advanced disease. Here we review the current and potential future treatments for
      advanced-stage CTCL. RECENT FINDINGS: Heterogeneity of treatment choice has been
      demonstrated both in US and non-US centers. Systemic treatment choice is
      currently guided by prognostic features, incorporating stage, immunophenotypic
      and molecular findings, and patient-specific factors such as age and
      comorbidities. Randomized controlled studies are uncommon, and the literature is
      composed predominantly of retrospective, cohort, and early-phase studies.
      International consensus guidelines are available; however, the lack of
      comparative trials means that there is no clear algorithmic approach to
      treatment. This review article reports on the systemic treatment options in
      current use for advanced CTCL, and on the possible future therapies,
      acknowledging that an algorithmic approach is not yet forthcoming to guide
      treatment prioritization.

PMID- 29572584
TI  - Noise reduction technology reduces radiation dose in chronic total occlusions
      percutaneous coronary intervention: a propensity score-matched analysis.
AB  - Chronic total occlusions (CTO) percutaneous coronary intervention (PCI) is
      associated with high radiation dose. Our study aim was to evaluate the impact of
      the implementation of a noise reduction technology (NRT) on patient radiation
      dose during CTO PCI. A total of 187 CTO PCIs performed between February 2016 and
      May 2017 were analyzed according to the angiographic systems utilized: Standard
      (n = 60) versus NRT (n = 127). Propensity score matching (PSM) was performed to
      control for differences in baseline characteristics. Primary endpoints were
      Cumulative Air Kerma at Interventional Reference Point (AK at IRP), which
      correlates with patient's tissue reactions; and Kerma Area Product (KAP), a
      surrogate measure of patient's risk of stochastic radiation effects. An
      Efficiency Index (defined as fluoroscopy time/AK at IRP) was calculated for each
      procedure. Image quality was evaluated using a 5-grade Likert-like scale. After
      PSM, n = 55 pairs were identified. Baseline and angiographic characteristics were
      well matched between groups. Compared to the Standard system, NRT was associated
      with lower AK at IRP [2.38 (1.80-3.66) vs. 3.24 (2.04-5.09) Gy, p = 0.035], a
      trend towards reduction for KAP [161 (93-244) vs. 203 (136-363) Gycm2, p =
      0.069], and a better Efficiency Index [16.75 (12.73-26.27) vs. 13.58 (9.92-17.63)
      min/Gy, p = 0.003]. Image quality was similar between the two groups (4.39 +/-
      0.53 Standard vs. 4.34 +/- 0.47 NRT, p = 0.571). In conclusion, compared with a
      Standard system, the use of NRT in CTO PCI is associated with lower patient
      radiation dose and similar image quality.

PMID- 29572585
TI  - Comparison of silage and hay of dwarf Napier grass (Pennisetum purpureum) fed to
      Thai native beef bulls.
AB  - Both quantity and quality of forages are important in dry season feeding. Eight
      Thai native beef bulls were arranged in a Completely randomized design to
      evaluate dwarf Napier namely Sweet grass (Pennisetum purpureum cv. Mahasarakham)
      preserved as silage or hay on feed intake, digestibility, and rumen fermentation.
      The animals were fed with forage ad libitum supplemented with concentrate mixture
      at 1.0% of BW for 21 days; data were collected during the last 7 days. The
      results showed that there were differences (P < 0.05) between treatments in dry
      matter (DM) intake, DM digestibility, and ruminal pH, in which hay feeding gave
      enhanced feed intake and more favorable ruminal pH. Nevertheless, mean ruminal
      ammonia nitrogen, total volatile fatty acids (TVFAs), proportion of VFAs,
      bacterial and protozoal population, and blood urea nitrogen were similar (P >
      0.05) in animals fed silage and hay. Sweet grass is better preserved as hay
      rather than silage.

PMID- 29572586
TI  - Elevated lipocalin-2 level in aqueous humor of patients with central retinal vein
      occlusion.
AB  - PURPOSE: To assess the concentrations of lipocalin-2 (LCN2) in the serum and the
      aqueous humor of patients with central retinal vein occlusion (CRVO). METHODS:
      The concentrations of LCN2 in the serum and aqueous humor of 16 cataract patients
      and 16 patients with CRVO with macular edema were compared. Collection of aqueous
      samples was conducted in the operating theater under sterile conditions and just
      prior to intravitreal ranibizumab injection or cataract surgery. LCN2 levels in
      serum and aqueous humor samples were measured using a commercial kit (human
      lipocalin-2/NGAL PicoKine ELISA Kit, MyBioSource Inc., USA; Catalog No:
      MBS175829) based on standard sandwich enzyme-linked immunosorbent assay
      technology. RESULTS: The concentrations of LCN2 in the aqueous humors of the CRVO
      group were higher than those of the control group (p = 0.021). There was no
      significant difference in serum LCN2 level between the two groups (p = 0.463).
      CONCLUSIONS: Concentrations of LCN2 in aqueous humor are increased in CRVO. LCN2
      may be part of a pro-catabolic phenotype, and it may play an important role in
      the dreaded complications of CRVO, such as macular edema, macular ischemia, and
      neovascularization, which lead to blindness.

PMID- 29572587
TI  - Neonatal Abstinence Syndrome (NAS) in Southwestern Border States: Examining
      Trends, Population Correlates, and Implications for Policy.
AB  - Introduction Neonatal abstinence syndrome (NAS) is withdrawal syndrome in
      newborns following birth and is primarily caused by maternal drug use during
      pregnancy. This study examines trends, population correlates, and policy
      implications of NAS in two Southwest border states. Materials and Methods A cross
      sectional analysis of Hospital Inpatient Discharge Data (HIDD) was utilized to
      examine the incidence of NAS in the Southwest border states of Arizona (AZ) and
      New Mexico (NM). All inpatient hospital births in AZ and NM from January 1, 2008
      through December 31, 2013 with ICD9-CM codes for NAS (779.5), cocaine (760.72),
      or narcotics (760.75) were extracted. Results During 2008-2013 there were 1472
      NAS cases in AZ and 888 in NM. The overall NAS rate during this period was 2.83
      per 1000 births (95% CI 2.68-2.97) in AZ and 5.31 (95% CI 4.96-5.66) in NM. NAS
      rates increased 157% in AZ and 174% in NM. NAS newborns were more likely to have
      low birth weight, have respiratory distress, more likely to have feeding
      difficulties, and more likely to be on state Medicaid insurance. AZ border region
      (border with Mexico) had NAS rates significantly higher than the state rate (4.06
      per 1000 births [95% CI 3.68-4.44] vs. 2.83 [95% CI 2.68-2.97], respectively). In
      NM, the border region rate (2.09 per 1000 births [95% CI 1.48-2.69]) was
      significantly lower than the state rate (5.31 [95% CI 4.96-5.66]). Conclusions
      Despite a dramatic increase in the incidence of NAS in the U.S. and, in
      particular, the Southwest border states of AZ and NM, there is still scant
      research on the overall incidence of NAS, its assessment in the southwest border,
      and associated long-term outcomes. The Healthy Border (HB) 2020 binational
      initiative of the U.S.-Mexico Border Health Commission is an initiative that
      addresses several public health priorities that not only include chronic and
      degenerative diseases, infectious diseases, injury prevention, maternal and child
      health but also mental health and addiction. The growing opioid epidemic and rise
      in NAS cases in the Southwest border, as partially shown in this study, provides
      another opportunity to track health illnesses and outcomes in the Southwest
      border, especially because there are targeted resources through High Intensity
      Drug Trafficking Areas (HIDTA) funding.

PMID- 29572589
TI  - Low-flow anaesthesia with a fixed fresh gas flow rate.
AB  - During the wash-in period in low flow anaesthesia (LFA), high fresh gas flow is
      used to achieve the desired agent concentration. In this study, we aimed to
      evaluate the safety of fixed 1 L/min fresh gas flow desflurane anaesthesia in
      both the wash-in and maintenance periods in patients including the obese ones.
      104 patients undergoing surgery under general anaesthesia were included. After
      endotracheal intubation, fresh gas flow was reduced to 1 L/min and the desflurane
      vaporizer was set at 18%. The time from opening the vaporizer to end-tidal
      desflurane concentration reaching 0.7 MAC was recorded (MAC 0.7 time). Throughout
      the surgery, hemodynamic variables, FIO2, MAC and BIS values were observed. MAC
      0.7 time, BIS and MAC values at the start of surgery, number of adjustments in
      vaporizer settings, desflurane consumption were recorded. The average MAC 0.7
      time was 2.9 +/- 0.5 min. MAC and BIS values at the start of the surgery were 0.7
      (0.6-0.8) and 39 +/- 8.5 respectively. No individual patient had a BIS value
      above 60 throughout the surgery. Hemodynamic variables were stable and FIO2 did
      not fall below 30% in any patient. The number of adjustments in vaporizer
      settings was 56. Average desflurane consumption was 0.33 +/- 0.05 mL/min. We
      demonstrated that LFA without use of initial high fresh gas flow during the wash
      in period is an effective, safe and economic method which is easy to perform.

PMID- 29572588
TI  - The intracellular distribution of inorganic carbon fixing enzymes does not
      support the presence of a C4 pathway in the diatom Phaeodactylum tricornutum.
AB  - Diatoms are unicellular algae and important primary producers. The process of
      carbon fixation in diatoms is very efficient even though the availability of
      dissolved CO2 in sea water is very low. The operation of a carbon concentrating
      mechanism (CCM) also makes the more abundant bicarbonate accessible for
      photosynthetic carbon fixation. Diatoms possess carbonic anhydrases as well as
      metabolic enzymes potentially involved in C4 pathways; however, the question as
      to whether a C4 pathway plays a general role in diatoms is not yet solved. While
      genome analyses indicate that the diatom Phaeodactylum tricornutum possesses all
      the enzymes required to operate a C4 pathway, silencing of the pyruvate
      orthophosphate dikinase (PPDK) in a genetically transformed cell line does not
      lead to reduced photosynthetic carbon fixation. In this study, we have determined
      the intracellular location of all enzymes potentially involved in C4-like carbon
      fixing pathways in P. tricornutum by expression of the respective proteins fused
      to green fluorescent protein (GFP), followed by fluorescence microscopy.
      Furthermore, we compared the results to known pathways and locations of enzymes
      in higher plants performing C3 or C4 photosynthesis. This approach revealed that
      the intracellular distribution of the investigated enzymes is quite different
      from the one observed in higher plants. In particular, the apparent lack of a
      plastidic decarboxylase in P. tricornutum indicates that this diatom does not
      perform a C4-like CCM.

PMID- 29572590
TI  - Protein profiling as early detection biomarkers for TiO2 nanoparticle toxicity in
      Daphnia magna.
AB  - The mode of action for nanoparticle (NP) toxicity in aquatic organisms is not yet
      fully understood. In this work, a strategy other than toxicity testing was
      applied to Daphnia magna exposed to TiO2-NPs: the use of nuclear microscopy and
      the assessment of protein profile. D. magna is a keystone species broadly used as
      a model system in ecotoxicology. Titanium (Ti) was found in the D. magna
      digestive tract, mainly in the gut. The penetration of Ti into the epithelial
      region was greater at higher exposure levels and also observed in eggs in the
      brood pouch. The protein profile of individuals exposed to different
      concentrations showed that 2.8 and 5.6 mg/L TiO2-NP concentrations induced an
      over-expression of the majority of proteins, in particular proteins with
      molecular weight of ~120, 85 and 15 kDa, while 11.2 mg/L TiO2-NP had an
      inhibitory effect on protein expression. The Matrix-assisted laser desorption
      ionization with tandem time of flight mass spectrometry (MALDI-TOF/TOF MS)
      analysis of these proteins consistently identified them as vitellogenin (Vtg)
      like proteins, associated with enzymes involved in redox balance. These results
      indicate that Vtg-like proteins are up-regulated in D. magna exposed to TiO2-NPs.
      Vitellogenesis is associated with the reproduction system, suggesting that TiO2
      NP exposure can impair reproduction by affecting this process. The precise mode
      of action of TiO2-NPs is still unclear and the results from this study are a
      first attempt to identify specific proteins as potential markers of TiO2-NP
      toxicity in D. magna, providing useful information for future research.

PMID- 29572592
TI  - Green Therapy of Cancer: A Promising Grope for Anticancer Strategy by Modern
      Chinese Medicine.

PMID- 29572591
TI  - Impact of peri-operative blood transfusion on post-operative infections after
      radical gastrectomy for gastric cancer: a propensity score matching analysis
      focusing on the timing, amount of transfusion and role of leukocyte depletion.
AB  - PURPOSE: Allogeneic blood transfusions (BTF) are sometimes inevitable during
      radical gastrectomy with lymphadenectomy for advanced gastric cancer. The aim of
      this retrospective study was to investigate the association between BTF and post
      operative infections, focusing on the impact of timing, amount of transfusion and
      the role of leukocyte depletion. METHODS: The study cohort was 2064 patients who
      underwent gastrectomy for gastric cancer from November 2010 to August 2017. The
      association between BTF and post-operative infections was estimated by univariate
      and multivariate analyses after propensity score matching. Subgroup analysis was
      performed according to the timing and amount of transfusion, and leukocyte
      depletion or not. RESULTS: Out of a total 2064 patients, 426 (20.6%) received
      peri-operative BTF. After one-to-one matching, 361 pairs of patients were
      included for further analysis, of who 68 (9.4%) developed infections.
      Multivariate analysis identified that an operation time >= 240 min, combined
      multi-organ resection, BTF and BMI >= 25 kg/m2 were independent risk factors for
      post-operative infection. Patients given a high-volume (> 7.5 U), intra
      operatively of leukocyte-non-depleted BTF had the highest risk of developing
      infections clarified by subgroup analysis. CONCLUSION: Infection was the most
      common complication following gastrectomy for gastric cancer and BTF was
      identified as an independent risk factor by propensity score matching and
      multivariate analyses. The timing, amount of transfusion and leukocyte depletion
      had an impact on the incidence of infection. To decrease infection, BTF should be
      avoided where possible, particularly during operation, with a large amount and
      leukocyte-not-depleted blood.

PMID- 29572593
TI  - In response to Letter regarding "Meta-analysis of 18F-FDG PET/CT in the diagnosis
      of infective endocarditis".

PMID- 29572594
TI  - Blood pool and tissue phase patient motion effects on 82rubidium PET myocardial
      blood flow quantification.
AB  - BACKGROUND: Patient motion can lead to misalignment of left ventricular volumes
      of interest and subsequently inaccurate quantification of myocardial blood flow
      (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We
      aimed to identify the prevalence of patient motion in both blood and tissue
      phases and analyze the effects of this motion on MBF and MFR estimates. METHODS:
      We selected 225 consecutive patients that underwent dynamic stress/rest rubidium
      82 chloride (82Rb) PET imaging. Dynamic image series were iteratively
      reconstructed with 5- to 10-second frame durations over the first 2 minutes for
      the blood phase and 10 to 80 seconds for the tissue phase. Motion shifts were
      assessed by 3 physician readers from the dynamic series and analyzed for
      frequency, magnitude, time, and direction of motion. The effects of this motion
      isolated in time, direction, and magnitude on global and regional MBF and MFR
      estimates were evaluated. Flow estimates derived from the motion corrected images
      were used as the error references. RESULTS: Mild to moderate motion (5-15 mm) was
      most prominent in the blood phase in 63% and 44% of the stress and rest studies,
      respectively. This motion was observed with frequencies of 75% in the septal and
      inferior directions for stress and 44% in the septal direction for rest. Images
      with blood phase isolated motion had mean global MBF and MFR errors of 2%-5%.
      Isolating blood phase motion in the inferior direction resulted in mean MBF and
      MFR errors of 29%-44% in the RCA territory. Flow errors due to tissue phase
      isolated motion were within 1%. CONCLUSIONS: Patient motion was most prevalent in
      the blood phase and MBF and MFR errors increased most substantially with motion
      in the inferior direction. Motion correction focused on these motions is needed
      to reduce MBF and MFR errors.

PMID- 29572595
TI  - An improved indirect ELISA for specific detection of antibodies against classical
      swine fever virus based on structurally designed E2 protein expressed in
      suspension mammalian cells.
AB  - Classical swine fever (CSF), which is caused by classical swine fever virus
      (CSFV), is a highly contagious disease of pigs. CSFV is genetically and
      serologically related to bovine viral diarrhea virus (BVDV), a ruminant
      pestivirus. However, currently available ELISAs based on the full-length E2
      protein of CSFV cannot discriminate anti-CSFV from anti-BVDV antibodies. In this
      study, a truncated CSFV E2 protein (amino acids 690 to 879) covering antigenic
      domains B/C/D/A (E2B/C/D/A) was designed based on homologous modeling according
      to the crystal structure of the BVDV E2 protein. The E2B/C/D/A protein was
      expressed in CHO cells adapted to serum-free suspension culture, and an indirect
      ELISA (iELISA) was established based on the recombinant protein. No serological
      cross-reaction was observed for anti-BVDV sera in the iELISA. When testing 282
      swine serum samples, the iELISA displayed a high sensitivity (119/127, 93.7%) and
      specificity (143/155, 92.3%), with an agreement of 92.9% (262/282) and 92.2%
      (260/282) with virus neutralization test and the IDEXX CSFV blocking ELISA,
      respectively. Taken together, the newly developed iELISA is highly specific and
      sensitive and able to differentiate anti-CSFV from anti-BVDV antibodies.

PMID- 29572596
TI  - Smacoviridae: a new family of animal-associated single-stranded DNA viruses.
AB  - Smacoviruses have small (~2.3-2.9 kb), circular single-stranded DNA genomes
      encoding rolling circle replication-associated proteins (Rep) and unique capsid
      proteins. Although smacoviruses are prevalent in faecal matter of various
      vertebrates, including humans, none of these viruses have been cultured thus far.
      Smacoviruses display ~45% genome-wide sequence diversity, which is very similar
      to that found within other families of circular Rep-encoding single-stranded
      (CRESS) DNA viruses, including members of the families Geminiviridae (46%
      diversity) and Genomoviridae (47% diversity). Here, we announce the creation of a
      new family Smacoviridae and describe a sequence-based taxonomic framework which
      was used to classify 83 smacovirus genomes into 43 species within six new genera,
      Bovismacovirus (n=3), Cosmacovirus (n=1), Dragsmacovirus (n=1), Drosmacovirus
      (n=3), Huchismacovirus (n=7), and Porprismacovirus (n=28). As in the case of
      genomoviruses, the species demarcation is based on the genome-wide pairwise
      identity, whereas genera are established based on the Rep amino acid sequence
      identity coupled with strong phylogenetic support. A similar sequence-based
      taxonomic framework should guide the classification of an astonishing diversity
      of other uncultured and currently unclassified CRESS DNA viruses discovered by
      metagenomic approaches.

PMID- 29572597
TI  - Correction to: Ectopic delivery of miR-200c diminishes hepatitis C virus
      infectivity through transcriptional and translational repression of Occludin.
AB  - The author would like to correct the errors in the online published article.

PMID- 29572598
TI  - Determination of Quality Criteria that Allow Differentiation Between Honey
      Adulterated with Sugar and Pure Honey.
AB  - This study used various parameters of honey to develop a potentially more robust
      approach to the detection of adulterated honey. For this purpose, 25 multifloral,
      natural honey samples and 20 samples of adulterated honey produced by bees that
      had been fed supplementary sucrose syrup were analysed. The mean total phenolic
      content of the natural honeys was considerably higher than in the adulterated
      honeys at 157 +/- 13 and 35.2 +/- 7.3 mg GAE/100 g, respectively. Similarly,
      considerable variation was determined between natural and adulterated honeys in
      terms of total flavonoids (3.3 +/- 0.3 and 2.1 +/- 0.4 mg QE/100 g,
      respectively), antiradical activity (87.9 +/- 12 and 163 +/- 11 mg/mL,
      respectively) and proline content (202 +/- 26 and 71.1 +/- 21.6 mg/kg,
      respectively.) The potassium, phosphorus, calcium and magnesium contents of
      natural honeys were also higher than in adulterated honeys (P < 0.01). In
      conclusion, the determination of the proline level, phenolic content, antioxidant
      activity and mineral profile may collectively provide a more holistic method
      approach to the differentiation of natural and adulterated honey, and also for
      comparing their food values.

PMID- 29572599
TI  - Laparoscopic fenestration for a huge symptomatic splenic cyst in a patient with
      Gaucher's disease.
AB  - A 34-year-old woman visited our hospital for treatment of a huge splenic cyst
      with epigastric pain. She had been diagnosed with Gaucher's disease (Type 1) at 3
      years of age and had been receiving enzyme replacement therapy (ERT) from 15
      years of age. Abdominal MRI showed a low-intensity area, 30 cm in diameter, with
      a well-defined border on T1-weighted images. The patient underwent laparoscopic
      fenestration of the huge splenic cyst for relief of worsening epigastric pain
      caused by the cyst. The cyst contained 2,500 ml of brownish-red fluid. The
      patient recovered satisfactorily and was discharged on postoperative day 11.
      Gaucher's disease is an extremely rare metabolic disease; only about 6,000
      patients are registered in the International Collaborative Gaucher Group Gaucher
      Registry. An extremely rare case of a huge symptomatic splenic cyst treated by
      laparoscopic fenestration in a patient with Gaucher's disease is described.

PMID- 29572600
TI  - Decreased Cerebral Blood Flow in Mesial Thalamus and Precuneus/PCC during
      Midazolam Induced Sedation Assessed with ASL.
AB  - While some previous work suggests that midazolam-induced light sedation results
      from the functional disconnection within resting state network, little is known
      about the underlying alterations of cerebral blood flow (CBF) associated with its
      effects. A randomized, double-blind, within-subject, cross-over design was
      adopted, while 12 healthy young volunteers were scanned with arterial spin
      labeling (ASL) perfusion MRI both before and after an injection of either saline
      or midazolam. The contrast of MRI signal before and after midazolam
      administration revealed the CBF decrease in the bilateral mesial thalamus and
      precuneus/posterior cingulate cortex (PCC). These effects were confirmed after
      controlling for any effect of injection as well as head motions. These findings
      provide new evidences that midazolam-induced light sedation is related to the
      disruption of cortical functional integration, and have new implications to the
      neural basis of consciousness.

PMID- 29572601
TI  - Multi-Modality Cascaded Convolutional Neural Networks for Alzheimer's Disease
      Diagnosis.
AB  - Accurate and early diagnosis of Alzheimer's disease (AD) plays important role for
      patient care and development of future treatment. Structural and functional
      neuroimages, such as magnetic resonance images (MRI) and positron emission
      tomography (PET), are providing powerful imaging modalities to help understand
      the anatomical and functional neural changes related to AD. In recent years,
      machine learning methods have been widely studied on analysis of multi-modality
      neuroimages for quantitative evaluation and computer-aided-diagnosis (CAD) of AD.
      Most existing methods extract the hand-craft imaging features after image
      preprocessing such as registration and segmentation, and then train a classifier
      to distinguish AD subjects from other groups. This paper proposes to construct
      cascaded convolutional neural networks (CNNs) to learn the multi-level and
      multimodal features of MRI and PET brain images for AD classification. First,
      multiple deep 3D-CNNs are constructed on different local image patches to
      transform the local brain image into more compact high-level features. Then, an
      upper high-level 2D-CNN followed by softmax layer is cascaded to ensemble the
      high-level features learned from the multi-modality and generate the latent
      multimodal correlation features of the corresponding image patches for
      classification task. Finally, these learned features are combined by a fully
      connected layer followed by softmax layer for AD classification. The proposed
      method can automatically learn the generic multi-level and multimodal features
      from multiple imaging modalities for classification, which are robust to the
      scale and rotation variations to some extent. No image segmentation and rigid
      registration are required in pre-processing the brain images. Our method is
      evaluated on the baseline MRI and PET images of 397 subjects including 93 AD
      patients, 204 mild cognitive impairment (MCI, 76 pMCI +128 sMCI) and 100 normal
      controls (NC) from Alzheimer's Disease Neuroimaging Initiative (ADNI) database.
      Experimental results show that the proposed method achieves an accuracy of 93.26%
      for classification of AD vs. NC and 82.95% for classification pMCI vs. NC,
      demonstrating the promising classification performance.

PMID- 29572602
TI  - Survivorship care plans: are randomized controlled trials assessing outcomes that
      are relevant to stakeholders?
AB  - PURPOSE: The purpose of this study was to compare outcomes assessed in extant
      randomized controlled trials (RCTs) to outcomes that stakeholders expect from
      survivorship care plans (SCPs). To facilitate the transition from active
      treatment to follow-up care for the 15.5 million US cancer survivors, many
      organizations require SCP use. However, results of several RCTs of SCPs'
      effectiveness have been null, possibly because they have evaluated outcomes on
      which SCPs should be expected to have limited influence. Stakeholders (e.g.,
      survivors, oncologists) may expect outcomes that differ from RCTs' outcomes.
      METHODS: We identified RCTs' outcomes using a PubMed literature review. We
      identified outcomes that stakeholders expect from SCPs using semistructured
      interviews with stakeholders in three healthcare systems in the USA and Canada.
      Finally, we mapped RCTs' outcomes onto stakeholder-identified outcomes. RESULTS:
      RCT outcomes did not fully address outcomes that stakeholders expected from SCPs,
      and RCTs assessed outcomes that stakeholders did not expect from SCPs. RCTs often
      assessed outcomes only from survivors' perspectives. CONCLUSIONS: RCTs of SCPs'
      effectiveness have not assessed outcomes that stakeholders expect. To better
      understand SCPs' effectiveness, future RCTs should assess outcomes of SCP use
      that are relevant from the perspective of multiple stakeholders. IMPLICATIONS FOR
      CANCER SURVIVORS: SCPs' effectiveness may be optimized when used with an eye
      toward outcomes that stakeholders expect from SCPs. For survivors, this means
      using SCPs as a map to guide them with respect to what kind of follow-up care
      they should seek, when they should seek it, and from whom they should seek it.

PMID- 29572603
TI  - Risk factor analysis of recanalization and retreatment for patients with
      endovascular treatment of internal carotid artery bifurcation aneurysms.
AB  - PURPOSE: Only a few reports of internal carotid artery (ICA) bifurcation
      aneurysms using the endovascular technique have been published in the current
      literature. The purpose of this study was to assess how multiple risk factors
      including angioarchitectural features of ICA bifurcation characteristics may have
      influenced aneurysmal rupture, recanalization, and retreatment. METHODS: Fifty
      one patients with 52 ICA bifurcation aneurysms treated with endovascular coiling
      between July 2003 and July 2015 were retrospectively analyzed. The patients'
      clinical records, endovascular reports, and clinical and angiographic outcomes
      were reviewed. We also evaluated risk factors for recanalization and retreatment,
      including the angioarchitectural anatomy. RESULTS: The clinical outcomes were
      observed to be satisfactory in 49 patients (96.0%) and unfavorable in 2 patients
      (4.0%). The risk factor for aneurysmal rupture was young age (P = 0.024).
      Symptomatic complications due to thromboembolism occurred in 1.9% of cases; no
      patients suffered a fatal complication. Eleven of 52 ICA bifurcation aneurysms
      (21.2%) were recanalized within an average of 54.3 +/- 33.5 months of follow-up.
      Among the aneurysms, 4 (7.7%) underwent recoiling. Multivariate analysis showed
      that ruptured aneurysms (P = 0.006) and a lower packing density (P = 0.048) were
      risk factors for recanalization. A lower packing density was the only risk factor
      for retreatment (P = 0.019). CONCLUSION: Endovascular treatment of ICA
      bifurcation aneurysms is considered safe and acceptable. This study showed that
      the ICA bifurcation aneurysms ruptured more frequently at a younger age. A higher
      packing density has been shown to reduce major recanalization and retreatment.

PMID- 29572604
TI  - Intrathecal gadolinium-enhanced MR cisternography in patients with otorhinorrhea:
      10-year experience of a tertiary referral center.
AB  - PURPOSE: Despite a considerable amount of literature that has been published
      about the use of intrathecal gadolinium-enhanced MR cisternography (IGE-MRC),
      there is still relatively lack of evidence as to its long-term effects. Our
      purpose in this study was twofold: firstly, to assess the long-term safety of the
      IGE-MRC; secondly, to evaluate the diagnostic performance of IGE-MRC for
      detecting cerebrospinal fluid (CSF) leak in otorhinorrhea patients. METHODS: We
      retrospectively reviewed our imaging and clinical database for the patients
      admitted to our department for the evaluation of their otorhinorrhea between 2008
      and 2017. Two radiologists evaluated the imaging studies independently. Consensus
      data was used in the analysis. Medical record review and phone call were used for
      the long-term follow-up. RESULTS: The retrospective review yielded 166 patients.
      Rhinorrhea was present in 150 (90.4%) patients and otorrhea in 16 (9.6%)
      patients. Overall, 67 patients (40.5% of all patients) underwent operation for
      repair of the CSF leak site. Beta-transferrin test was available and positive in
      57 (34.3%) patients. Overall sensitivity of IGE-MRC and paranasal high-resolution
      CT (HRCT) was 89.3 and 72%, respectively. Within the first 24 h after the
      procedure, none of the patients experienced a significant complication or adverse
      reaction. Ninety-nine patients (59.6%) had medical record and telephone follow
      up. The mean follow-up duration with call was 37.1 months. Three (3%) patients
      complained about severe headache 3-4 weeks after the procedure. CONCLUSIONS: IGE
      MRC is a minimally invasive and highly sensitive imaging technique. No adverse
      side effect during our long-term follow-up might strengthen and support the
      safety of IGE-MRC.

PMID- 29572605
TI  - Inflammatory Bowel Disease Across the Age Continuum: Similarity and Disparity.
AB  - OBJECTIVES: To identify similarities and differences between the pediatric-onset
      and adult-onset Inflammatory Bowel Disease (IBD) based cohorts and further
      characterize the pediatric cohort. METHODS: A retrospective analysis of pediatric
      patients attending the tertiary referral care gastroenterology center from 2004
      to 2016 was conducted. All the patients were clinically evaluated, investigated
      and followed up at the centre. RESULTS: Sixty five patients with pediatric IBD
      were compared with 216 patients with adult-onset IBD. The Ulcerative colitis:
      Crohn's disease (UC:CD) ratio was higher in adult-onset population (2.29:1 vs.
      1.7:1). Predominant symptoms in pediatric UC were diarrhea and passage of blood
      in stools; whereas those in pediatric CD were abdominal pain and failure to gain
      weight. Ulcerative proctitis was less common (2.4% vs. 18.8%; p = 0.009) and an
      extensive disease (pancolitis) was more common in the pediatric population (73.1%
      vs. 30.2%; p < 0.00001). Adult CD had higher L3 (33.3% vs. 46.1%; p = 0.28)
      disease; whereas in pediatric CD, L1 disease (37.5% vs. 32.3%; p = 0.65) was
      predominant. There was no difference with respect to penetrating and stricturing
      complications of CD in adults vs. children (20.8% vs. 23.1%; p = 0.974). 5-ASA
      agents were used more commonly in the pediatric IBD population (96.9% vs. 79.9%;
      p = 0.0034) as compared to adults whereas corticosteroids (87.5% vs. 76.9%; p =
      0.28) and infliximab (25% vs. 9.2%; p = 0.054) were used more frequently in the
      pediatric CD subgroup as compared to adult CD subgroup. CONCLUSIONS: IBD has
      significant disease heterogeneity according to the age of onset. Pediatric IBD
      has distinctive features that set it apart from adult-onset IBD.

PMID- 29572606
TI  - Vascular liver diseases on the clinical side: definitions and diagnosis, new
      concepts.
AB  - The components of the hepatic vascular system (hepatic arteries, portal and
      hepatic veins, sinusoids, and lymphatics) can be damaged by various types of
      injury. Each of the resulting conditions is rare, which has limited knowledge and
      awareness. In the last two decades, international collaborations have allowed to
      reach critical masses of data, which has driven significant progresses in
      understanding and management of vascular disorders of the liver. The present
      paper discusses definitions, denominations, and diagnosis of such vascular
      disorders with the exception of those affecting hepatic arteries. Evolving
      pathogenic or pathophysiologic views relevant to the clinical aspects are also
      overviewed.

PMID- 29572607
TI  - Invasive forest pathogens in Europe: Cross-country variation in public awareness
      but consistency in policy acceptability.
AB  - Political action can reduce introductions of diseases caused by invasive forest
      pathogens (IPs) and public support is important for effective prevention. The
      public's awareness of IP problems and the acceptability of policies aiming to
      combat these pathogens were surveyed in nine European countries (N = 3469).
      Although awareness of specific diseases (e.g., ash dieback) varied, problem
      awareness and policy acceptability were similar across countries. The public was
      positive towards policies for informational measures and stricter standards for
      plant production, but less positive towards restricting public access to
      protected areas. Multilevel models, including individual and country level
      variables, revealed that media exposure was positively associated with awareness
      of IP problems, and strengthened the link between problem awareness and policy
      acceptability. Results suggest that learning about IPs through the media and
      recognizing the associated problems increase policy acceptability. Overall, the
      study elaborates on the anthropogenic dimension of diseases caused by IPs.

PMID- 29572608
TI  - Comment on "Safety of Human Papillomavirus Vaccines: An Updated Review".

PMID- 29572609
TI  - Comment on: "Safety of Human Papillomavirus Vaccines: An Updated Review".

PMID- 29572610
TI  - The application of the palliative prognostic index in predicting the life
      expectancy of patients in palliative care: a systematic review and meta-analysis.
AB  - BACKGROUND: The palliative prognostic index (PPI) is a commonly used tool to
      predict the life expectancy in palliative care patients. However, there is no
      universal cutoff, and the accuracy of different cutoffs varies. Therefore, we
      conducted this meta-analysis to explore the validity and accuracy of different
      PPI scores for different survival time in palliative care setting. METHODS:
      PubMed, Embase, Cochrane, Scopus and Chinese CNKI databases were searched to
      identify studies using the PPI as a prognostic tool to predict survival time in
      palliative care. We calculated pooled hazard ratios (HRs) with corresponding 95%
      confidence intervals (CIs), and subgroup analyses were also conducted by
      different cutoffs. After extracting data, we estimated the pooled sensitivity,
      specificity, positive predictive value, and negative predictive value. RESULTS:
      We identified 15 studies with 7455 assessments. Seven of these studies were
      synthesized for a combined HR. The pooled HR was 1.94 (95% CI 1.54-2.44) when
      cutoffs were 2 and 4, and 2.34 (95% CI 1.50-3.66) when cutoffs were 4 and 6. Of
      all the studies, 13 studies reported their accuracy, of which four studies were
      assessed by meta-analysis. The sensitivity of the PPI for 3-week survival ranged
      from 51 to 92% and specificity ranged from 60.0 to 94.0%, respectively. The
      sensitivity and specificity of the PPI for 6-week survival were from 46.0 to
      89.1% and from 51.7 to 84.4%, respectively. The pooled sensitivity and
      specificity of the PPI for 3-week survival were 68% (6 as cutoff) and 76% (6 as
      cutoff), respectively. As for 6-week survival prediction, the pooled sensitivity
      and specificity were 68% (4 as cutoff) and 82% (4 as cutoff), respectively.
      CONCLUSION: The PPI is a useful prognosticator of life expectancy of patients in
      palliative care, especially for patients with short survival time. However, there
      were no universal cutoff, and the predicted life span varies. Our data eliminated
      that using 4 and 6 as cutoffs can better predict the patients' survival time for
      3 or 6 weeks. Due to small number of studies and poor qualities of them, result
      may alter as more studies with better quality are enrolled in the future.

PMID- 29572611
TI  - Usefulness of a pleuroperitoneal shunt for treatment of refractory pleural
      effusion in a patient receiving maintenance hemodialysis.
AB  - Refractory pleural effusion can be a life-threatening complication in patients
      receiving maintenance hemodialysis. We report successful treatment of refractory
      pleural effusion using a Denver(r) pleuroperitoneal shunt in one such patient. A
      54-year-old Japanese man, who had previously undergone left nephrectomy, was
      admitted urgently to our department because of a high C-reactive protein (CRP)
      level, right pleural effusion, and right renal abscess. Because antibiotics
      proved ineffective and his general state was deteriorating, he underwent
      emergency insertion of a thoracic drainage tube and nephrectomy, and hemodialysis
      was started. Although his general state improved slowly thereafter, the pleural
      effusion, which was unilateral and transudative, remained refractory and
      therefore he needed to be on oxygenation. To control the massive pleural
      effusion, a pleuroperitoneal shunt was inserted. Thereafter, his respiratory
      condition became stable without oxygenation and he was discharged. His general
      condition has since been well. Although pleural effusion is a common complication
      of maintenance hemodialysis, few reports have documented the use of
      pleuroperitoneal shunt to control refractory pleural effusion. Pleuroperitoneal
      shunt has been advocated as an effective and low-morbidity treatment for
      refractory pleural effusion, and its use for some patients with recurrent pleural
      effusion has also been reported, without any severe complications. In the present
      case, pleuroperitoneal shunt improved the patient's quality of life sufficiently
      to allow him to be discharged home without oxygenation. Pleuroperitoneal shunt
      should be considered a useful treatment option for hemodialysis patients with
      refractory pleural effusion.

PMID- 29572612
TI  - Substrate selection of adenylation domains for nonribosomal peptide synthetase
      (NRPS) in bacillamide C biosynthesis by marine Bacillus atrophaeus C89.
AB  - Nonribosomal peptide synthetases (NRPSs) are multi-modular enzymes involved in
      the biosynthesis of natural products. Bacillamide C was synthesized by Bacillus
      atrophaeus C89. A nonribosomal peptide synthetase (NRPS) cluster found in the
      genome of B. atrophaeus C89 was hypothesized to be responsible for the
      biosynthesis of bacillamide C using alanine and cysteine as substrates. Here, the
      structure analysis of adenylation domains based on homologous proteins with known
      crystal structures indicated locations of the substrate-binding pockets.
      Molecular docking suggested alanine and cysteine as the potential substrates for
      the two adenylation domains in the NRPS cluster. Furthermore, biochemical
      characterization of the purified recombinant adenylation domains proved that
      alanine and cysteine were the optimum substrates for the two adenylation domains.
      The results provided the in vitro evidence for the hypothesis that the two
      adenylation domains in the NRPS of B. atrophaeus C89 preferentially select
      alanine and cysteine, respectively, as a substrate to synthesize bacillamide C.
      Furthermore, this study on substrates selectivity of adenylation domains provided
      basis for rational design of bacillamide analogs.

PMID- 29572613
TI  - Response of gastrointestinal melatonin, antioxidants, and digestive enzymes to
      altered feeding conditions in carp (Catla catla).
AB  - The purpose of present study was to ascertain whether the response of
      gastrointestinal (gut) melatonin to altered feeding conditions was related to the
      levels of different antioxidants and digestive enzymes in the same gut tissues of
      a sub-tropical carp (Catla catla). Accordingly, the fish were subjected to food
      deprivation for 4 or 8 days and separately to re-feeding for 4 or 8 or 12 days
      after deprivation of food for 8 days, and their gut tissue homogenates were used
      to measure the levels of melatonin, both enzymatic [superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST)]
      and non-enzymatic [reduced glutathione (GSH)] antioxidants, as well as different
      digestive enzymes (alpha-amylase, cellulase, protease, and lipase). Notably, the
      gut levels of melatonin, SOD, CAT, GPx, and GST underwent gradual increase with
      the progress of food deprivation, but a sudden fall after restoration of food
      supply for 4 days and a rise thereafter. Conversely, the activity of all the
      digestive enzymes significantly decreased after deprivation of food, but started
      increasing when food supply was reinforced. Gut melatonin concentrations by
      showing a positive correlation with the titers of different antioxidants (in both
      food-deprived and re-fed fish groups) and a negative (in food-deprived fish) or a
      positive (in re-fed fish) correlation with the activity of each digestive enzyme
      underlined possible physiological interplay between them. Collectively, our
      findings lend support to the hypothesis that gut melatonin response to altered
      feeding conditions in carp might be associated with the oxidative status as well
      as the digestive functions of the gastrointestinal tissues itself.

PMID- 29572614
TI  - A case of ruptured aneurysm of coronary-pulmonary artery fistula diagnosed after
      emergency thoracotomy.
AB  - BACKGROUND: Coronary fistulae are occasionally detected using echocardiography or
      coronary angiography. We report a patient with cardiac tamponade because of a
      ruptured aneurysm of a coronary artery fistula. CASE PRESENTATION: A 60-year-old
      man was referred to our hospital with sudden onset of chest pain and
      unconsciousness. He was initially diagnosed with cardiac tamponade for type A
      acute aortic dissection, and an emergency operation was performed. A large amount
      of bleeding was seen in the pericardium, but aortic dissection around the arch
      was not observed. Instead, a ruptured aneurysm of a coronary-pulmonary fistula
      was identified on the pulmonary artery root. The aneurysm was resected, and the
      fistula was closed by ligation. The patient's postoperative progress was good,
      and he was discharged on postoperative day 12 without any abnormalities on the
      coronary arteriogram. CONCLUSIONS: Preoperative diagnosis of the rupture of the
      small coronary artery aneurysm is difficult in such an emergency case, and this
      possibility should be considered in differential diagnosis when the CT image does
      not show typical aortic dissection.

PMID- 29572616
TI  - Tropheryma whipplei Infection (Whipple Disease) in the USA.
AB  - BACKGROUND: Whipple disease (WD) is an infection caused by the bacterium
      Tropheryma whipplei (TW). Few cases have been reported in the USA. AIMS: To
      report on the demographics, clinical manifestations, diagnostic findings,
      treatment, and outcomes of TW infection. METHODS: Cases of TW infection diagnosed
      from 1995 to 2010 were identified in three US referral centers and from 1995 to
      2015 in one. Definite classic WD was defined by positive periodic acid-Schiff
      (PAS) staining and probable WD by specific positive TW polymerase chain reaction
      (PCR) of intestinal specimens. Localized infections were defined by a positive TW
      PCR result from samples of other tissues/body fluids. RESULTS: Among the 33 cases
      of TW infections, 27 (82%) were male. Median age at diagnosis was 53 years (range
      11-75). Diagnosis was supported by a positive TW PCR in 29 (88%) and/or a
      positive PAS in 16 (48%) patients. Classic WD was the most frequent presentation
      (n = 18, 55%), with 14 definite and 4 probable cases. Localized infections (n =
      15, 45%) affected the central nervous system (n = 7), joints (n = 4), heart (n =
      2), eye (n = 1), and skeletal muscle (n = 1). Blood PCR was negative in 9 of 17
      (53%) cases at diagnosis. Ceftriaxone intravenously followed by trimethoprim and
      sulfamethoxazole orally was the most common regimen (n = 23, 70%). Antibiotic
      therapy resulted in clinical response in 24 (73%). CONCLUSIONS: TW infection can
      present as intestinal or localized disease. Negative small bowel PAS and PCR do
      not exclude the diagnosis of TW infection, and blood PCR is insensitive for
      active infection.

PMID- 29572617
TI  - Robotic Autotransplantation and Management of Post-transplant Anastomotic
      Strictures: the Future Is Here.
AB  - PURPOSE OF REVIEW: We set out to review the current published experience with
      robotic autotransplantation. Although the experience to date is limited, this
      surgery appears to be safe and technically feasible. We also examined the use of
      the robotic surgical platform for the management of post-transplant uretero
      vesical anastomotic strictures. RECENT FINDINGS: To date, only four reported
      cases of robotic autotransplantation have been described with two being performed
      completely intra-corporeally. An intra-corporeal approach is feasible for benign
      conditions, while malignant masses should be inspected and dissected extra
      corporeally. Ureteric strictures after renal transplantation are common. To date,
      the experience with robotic surgical management is limited but has also been
      shown to be safe and feasible. While robotic autotransplantation is still in its
      infancy, it is feasible and appears to be safe. Renal allograft function and
      surgical outcomes are favorable and provide patients the option to have a
      historically more morbid surgery performed with a minimally invasive approach.

PMID- 29572619
TI  - The Effect of Cognitive-Emotional Training on Post-traumatic Growth in Women with
      Breast Cancer in Middle East.
AB  - Overcoming distresses and negative consequences of serious crises such as cancers
      can lead to perception of positive changes in the patients. It is necessary to
      design and test the psychological interventions that can improve post-traumatic
      growth. The objective of this study was to determine the effect of cognitive
      emotional training on post-traumatic growth in women with breast cancer referred
      to the department of chemotherapy. This is a quasi-experimental study and it was
      performed on 85 patients with breast cancer who referred to an educational
      hospital in southeastern of Iran in 2017. The eligible patients were selected
      through convenience method sampling among the patients and they randomly
      allocated into intervention and control groups. The intervention group received
      five sessions of emotional-cognitive training in two sessions per week. Each
      session lasted 60-90 min. The posttest data were collected by post-traumatic
      growth inventory (PTGI) 20 weeks after the end of the last intervention session.
      Collected data were analyzed by SPSS software version 21.00 using independent t
      test, paired t test, and Chi-square tests for demographic analysis. The results
      indicated that there is no significant difference in both groups in terms of
      individual variables such as age, marriage, duration of disease, and degree
      progression of cancer. Although the mean of PTG scores in posttest and the mean
      of variations in the PTG scores in the intervention group were 77.48 +/- 11.18
      and 25.81 +/- 12.24, respectively, and it was significantly higher than the
      control group, 53.95 +/- 14.86 and 7.69 +/- 9, respectively (mean scores of PTG:
      p < .0001; mean changes of PTG: p < .001). According to the results of this
      study, cognitive-behavioral intervention had a positive and significant effect on
      post-traumatic growth in women with breast cancer. If intervention is found to be
      effective, cognitive and emotional strategies of such interventions could be
      integrated into daily clinical practice as a way to promote PTG in women who are
      being treated for breast cancer.

PMID- 29572618
TI  - The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis.
AB  - PURPOSE OF REVIEW: Statins are drugs developed to treat hypercholesterolemia. Its
      use in patients with liver disease has been limited because one of its potential
      and most feared side effects is hepatotoxicity. However, there is robust evidence
      that supports the safety of statins in this population in the absence of severe
      liver dysfunction. In this review, we will summarize the efficacy and safety of
      statins in cirrhosis. RECENT FINDINGS: Statins are effective in the treatment of
      dyslipidemia in patients with liver disease, because of their pleiotropic
      properties. These properties are independent of their effect on cholesterol
      levels, such as improving endothelial dysfunction or having antioxidant,
      antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic,
      or immunomodulation properties. Statins have been studied in other areas such as
      in treatment of portal hypertension, prevention of hepatocellular carcinoma,
      and/or protection against ischemia/reperfusion injury. Approved indications for
      statins in patients with cirrhosis are those of the general population, including
      dyslipidemia and increased cardiovascular risk. Compensated cirrhosis is not a
      contraindication. In patients with decompensated cirrhosis, statins should be
      prescribed with extreme caution at low doses, and with frequent monitoring of
      creatinine phosphokinase levels in order to detect adverse events in a timely
      fashion.

PMID- 29572615
TI  - Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art,
      Challenges and Research Directions.
AB  - Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran
      population, a fact which has focused a great deal of the attention of the VA's
      research and development efforts. A field-based meeting of CRC experts was
      convened to discuss both challenges and opportunities in precision medicine for
      CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium
      (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early
      detection and prevention. There was also a discussion of precision treatment
      involving fluorescence-guided surgery, targeted chemotherapies and
      immunotherapies, and personalized cancer treatment approaches. The overarching
      goal was to identify modalities that might ultimately lead to personalized cancer
      diagnosis and treatment. This review summarizes the findings of this VA field
      based meeting, in which much of the current knowledge on CRC prescreening and
      treatment was discussed. It was concluded that there is a need and an opportunity
      to identify new targets for both the prevention of CRC and the development of
      effective therapies for advanced disease. Also, developing methods integrating
      genomic testing with tumoroid-based clinical drug response might lead to more
      accurate diagnosis and prognostication and more effective personalized treatment
      of CRC.

PMID- 29572620
TI  - Groundwater fluoride contamination, probable release, and containment mechanisms:
      a review on Indian context.
AB  - Fluoride contamination in the groundwater has got great attention in last few
      decades due to their toxicity, persistent capacity and accumulation in human
      bodies. There are several sources of fluoride in the environment and different
      pathways to enter in the drinking water resources, which is responsible for
      potential effect on human health. Presence of high concentration of fluoride ion
      in groundwater is a major issue and it makes the water unsuitable for drinking
      purpose. Availability of fluoride in groundwater indicates various geochemical
      processes and subsurface contamination of a particular area. Fluoride-bearing
      aquifers, geological factors, rate of weathering, ion-exchange reaction,
      residence time and leaching of subsurface contaminants are major responsible
      factors for availability of fluoride in groundwater. In India, several studies
      have reported that the groundwater of several states are contaminated with high
      fluoride. The undesirable level of fluoride in groundwater is one of the most
      natural groundwater quality problem, which affects large portion of arid and
      semiarid regions of India. Rajasthan, Andhra Pradesh, Telangana, Tamil Nadu,
      Gujarat, and West Bengal are the relatively high-fluoride-contaminated states in
      India. Chronic ingestion of high doses of fluoride-rich water leads to fluorosis
      on human and animal. Over 66 million Indian populations are at risk due to excess
      fluoride-contaminated water. Therefore, groundwater contamination subject to
      undesirable level of fluoride needs urgent attention to understand the role of
      geochemistry, hydrogeology and climatic factors along with anthropogenic inputs
      in fluoride pollution.

PMID- 29572621
TI  - Blood-brain barrier leakage in relation to white matter hyperintensity volume and
      cognition in small vessel disease and normal aging.
AB  - Blood-brain barrier (BBB) leakage increases with age and is involved in the
      pathophysiology of cerebral small vessel disease (cSVD). We examined the
      relationship between BBB leakage and white matter hyperintensity (WMH) volume and
      cognition, in cSVD patients and healthy controls. Seventy-seven patients with
      clinically overt cSVD and thirty-nine age matched healthy controls underwent
      dynamic contract-enhanced and structural brain MRI and neuropsychological
      assessment. We quantified BBB leakage volume and rate in normal appearing white
      matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and
      lower leakage rate in WMH were associated with larger WMH volume in cSVD but not
      in controls. Higher leakage rate in NAWM was associated with lower scores on
      executive function and information processing speed in healthy controls, whereas
      no relation with cognition was found in cSVD patients. Our findings support the
      involvement of BBB leakage in cSVD and aging. They also suggest that the
      mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in
      cSVD compared with normal aging.

PMID- 29572622
TI  - Weight loss in men in late life and bone strength and microarchitecture: a
      prospective study.
AB  - : Weight loss in men in late life was associated with lower bone strength. In
      contrast, weight gain was not associated with a commensurate increase in bone
      strength. Future studies should measure concurrent changes in weight and
      parameters of bone strength and microarchitecture and evaluate potential causal
      pathways underlying these associations. INTRODUCTION: Our aim was to determine
      associations of weight loss with bone strength and microarchitecture. METHODS: We
      used data from 1723 community-dwelling men (mean age 84.5 years) who attended the
      MrOS study Year (Y) 14 exam and had high-resolution peripheral quantitative
      computed tomography (HR-pQCT) scans at >= 1 skeletal sites (distal tibia, distal
      radius, or diaphyseal tibia). Weight change from Y7 to Y14 exams (mean 7.3 years
      between exams) was classified as moderate weight loss (loss >= 10%), mild weight
      loss (loss 5 to < 10%), stable weight (< 5% change), or weight gain (gain >= 5%).
      Mean HR-pQCT parameters (95%CI) were calculated by weight change category using
      linear regression models adjusted for age, race, site, health status, body mass
      index, limb length, and physical activity. The primary outcome measure was
      estimated failure load. RESULTS: There was a nonlinear association of weight
      change with failure load at each skeletal site with different associations for
      weight loss vs. weight gain (p < 0.03). Failure load and total bone mineral
      density (BMD) at distal sites were lower with greater weight loss with 7.0-7.6%
      lower failure loads and 4.3-5.8% lower BMDs among men with moderate weight loss
      compared to those with stable weight (p < 0.01, both comparisons). Cortical, but
      not trabecular, BMDs at distal sites were lower with greater weight loss. Greater
      weight loss was associated with lower cortical thickness at all three skeletal
      sites. CONCLUSION: Weight loss in men in late life is associated with lower
      peripheral bone strength and total BMD with global measures reflecting cortical
      but not trabecular parameters.

PMID- 29572623
TI  - Fatal methemoglobinemia complicating alkaptonuria (ochronosis): a rare
      presentation.
AB  - A 61-year-old female died in hospital with multiple organ failure 4 weeks
      following presentation with acute kidney injury, hemolytic anemia and
      methemoglobinemia. At autopsy, brown to black discoloration of cartilages was
      observed. Histology revealed brown pigmentation of the hyaline cartilage, with
      focal full-thickness erosion of the articular hyaline cartilage, characteristic
      of alkaptonuria (ochronosis). Although alkaptonuria is rarely fatal, this case
      illustrates a rare acute fatal complication. Accumulation of circulating
      homgentisic acid secondary to acute derangement of renal function is believed to
      have overwhelmed the endogenous antioxidant processes, resulting in hemolysis and
      methemoglobinemia, which were refractory to treatment. Small numbers of cases
      have previously been reported in the literature in patients known to suffer with
      the disease, all of which were preceded by acute kidney injury. Whilst the
      clinical diagnosis of alkaptonuria may be challenging, the autopsy findings of
      this rare condition are striking and this case illustrates the utility of the
      autopsy, albeit retrospectively, in arriving at a diagnosis. To our knowledge
      this is the first reported case where previously undiagnosed alkaptonuria has
      presented with methemoglobinemia.

PMID- 29572624
TI  - Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in
      HIV and HCV: Strategies in the DAA Era.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the prevalence and
      clinical implications of the isolated anti-HBc serologic profile in HIV-infected
      individuals. We highlight the rare but important issue of HBV reactivation in the
      setting of HCV therapy and describe an approach to management. RECENT FINDINGS:
      The isolated anti-HBc pattern, a profile that most often indicates past exposure
      to HBV with waning anti-HBs immunity, is found commonly in HIV-infected
      individuals, particularly those with HCV. Some large cohort studies demonstrate
      an association with advanced liver disease, while others do not. Conversely, meta
      analyses have found an association between occult HBV infection (a component of
      the isolated anti-HBc pattern) and advanced liver disease and hepatocellular
      carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti
      HBc positivity, HBV reactivation has been reported in patients receiving HCV
      therapy. This phenomenon is likely the result of disinhibition of HBV with HCV
      eradication. In HIV-infected patients, the long-term liver outcomes associated
      with the isolated anti-HBc pattern remain to be fully elucidated, supporting the
      need for large cohort studies with longitudinal follow-up. HBV reactivation
      during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can
      inform algorithms for the screening and management of the isolated anti-HBc
      pattern in this population.

PMID- 29572626
TI  - Is visual activation associated with changes in cerebral high-energy phosphate
      levels?
AB  - Phosphorus magnetic resonance spectroscopy (31P MRS) has been employed before to
      assess phosphocreatine (PCr) and other high-energy phosphates in the visual
      cortex during visual stimulation with inconsistent results. We performed
      functional 31P MRS imaging in the visual cortex and control regions during a
      visual stimulation paradigm at an unprecedented sensitivity, exploiting a
      dedicated RF coil design at a 7 T MR system. Visual stimulation in a 3 min 24 s
      on-off paradigm in eight young healthy adults generated a clear BOLD effect with
      traditional 1H functional MRI in the visual cortex (average z score 9.9 +/- 0.2).
      However, no significant event-related changes in any of the 31P metabolite
      concentrations, linewidths (7.9 +/- 1.8 vs 7.8 +/- 1.9 Hz) or tissue pH (7.07 +/-
      0.13 vs 7.06 +/- 0.07) were detectable. Overall, our study of 31P MRSI in 15 cm3
      voxels had a detection threshold for changes in PCr, Pi and gamma-ATP between
      stimulation and rest of 5, 17 and 10%, respectively. In individual subjects, the
      mean coefficients of variance for PCr and Pi levels of control voxels were 6 +/-
      3 and 19 +/- 8% (three time point average of 3 min 24 s). Altogether this
      indicates that energy supply for neuronal activation at this temporal resolution
      does not drain global PCr resources.

PMID- 29572627
TI  - Functional impairment and risk of mortality in patients on chronic hemodialysis:
      results of the Lazio Dialysis Registry.
AB  - BACKGROUND: Functional impairment is associated with adverse outcomes in older
      people, as well as in patients on chronic hemodialysis. The aim of this study was
      to evaluate if functional impairment represents a risk factor for reduced
      survival in patients on chronic hemodialysis. METHODS: All incident chronic
      hemodialysis patients of Lazio, a large region of central Italy, registered in
      the Dialysis and Transplant Lazio Region Registry (DTLRR) in the period 2008-2013
      were considered eligible. Inclusion criteria were: age > 18 years, resident in
      Lazio, still doing dialysis after 90 days from incidence date, doing hemodialysis
      or hemodiafiltration treatment for > 9 h/week. Patients were stratified into
      three classes of functional activity: total autonomy, autonomy in some
      activities, and not self-sufficient. Functional activity was assessed for each
      patient by the referring physician for the DTLRR from the ~ 90 hemodialysis units
      of the Lazio region. Each patient was followed from date of first dialysis
      treatment to the end of the study (31/12/2015) or death or renal transplant,
      whichever occurred first. Cox proportional hazard models were performed to obtain
      mortality hazard ratios (HR), 95% confidence intervals (CI), for each class of
      functional activity adjusting for sex, age, country of birth, city of residence,
      body mass index (BMI), type of nephropathy, vascular access, previous nephrology
      counselling, weekly hours of hemodialysis, serum albumin, hemoglobin, and
      presence of comorbidities (e.g. vascular diseases, coronary disease, and
      diabetes). RESULTS: A total of 3356 patients were studied. In the whole follow-up
      period, 1622 deaths occurred (48%). Functional impairment was associated with the
      risk of mortality: compared to 'total autonomy', the HR for 'autonomy in some
      activities' was 1.30 [95% CI: 1.14-1.49] and for 'not self-sufficient' 1.71 [1.47
      1.99] (p for trend < 0.05). The number of evitable deaths attributable to reduced
      functional activity was 237. CONCLUSION: Functional impairment represents a risk
      factor for reduced survival in chronic hemodialysis patients. There is a need for
      early identification of patients who might benefit from interventions aimed at
      preventing, reversing or delaying the functional impairment.

PMID- 29572628
TI  - Correction to: Comparison between submucosal tunneling endoscopic resection and
      video-assisted thoracoscopic enucleation for esophageal submucosal tumors
      originating from the muscularis propria layer: a randomized controlled trial.
AB  - In the original article, there are two errors in Table 3: 1. There were 8
      patients undergoing VATE suffer from moderate fever, not 9. 2. In the fourth line
      of outcomes, saying "pneumothorax, moderate fever and moderate fever," "moderate
      fever" was repeated.

PMID- 29572625
TI  - Predicting personality from network-based resting-state functional connectivity.
AB  - Personality is associated with variation in all kinds of mental faculties,
      including affective, social, executive, and memory functioning. The intrinsic
      dynamics of neural networks underlying these mental functions are reflected in
      their functional connectivity at rest (RSFC). We, therefore, aimed to probe
      whether connectivity in functional networks allows predicting individual scores
      of the five-factor personality model and potential gender differences thereof. We
      assessed nine meta-analytically derived functional networks, representing social,
      affective, executive, and mnemonic systems. RSFC of all networks was computed in
      a sample of 210 males and 210 well-matched females and in a replication sample of
      155 males and 155 females. Personality scores were predicted using relevance
      vector machine in both samples. Cross-validation prediction accuracy was defined
      as the correlation between true and predicted scores. RSFC within networks
      representing social, affective, mnemonic, and executive systems significantly
      predicted self-reported levels of Extraversion, Neuroticism, Agreeableness, and
      Openness. RSFC patterns of most networks, however, predicted personality traits
      only either in males or in females. Personality traits can be predicted by
      patterns of RSFC in specific functional brain networks, providing new insights
      into the neurobiology of personality. However, as most associations were gender
      specific, RSFC-personality relations should not be considered independently of
      gender.

PMID- 29572629
TI  - A prospective randomized trial of EUS-guided tissue acquisition using a 25-gauge
      core biopsy needle with and without a stylet.
AB  - BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition has become the
      most effective method of obtaining specimens from a solid lesion adjacent to the
      gastrointestinal tract. No data exist regarding the use of a stylet in the core
      biopsy needle during EUS-guided tissue acquisition. The aims of this study were
      to evaluate the feasibility, safety, and diagnostic yield of a 25-gauge core
      biopsy needle without (S-) a stylet and to compare its performance with that of a
      25-gauge core biopsy needle with (S+) a stylet in patients with solid lesions
      adjacent to the gastrointestinal tract. METHODS: From November 2013 to January
      2016, we performed 114 EUS-guided tissue acquisitions for the diagnosis of solid
      lesions adjacent to the gastrointestinal tract in a randomized controlled trial.
      Patients were randomly assigned to the S+ group (n = 57) or the S- group (n =
      57). EUS-guided tissue acquisition was performed using a 25-gauge core biopsy
      needle without an on-site cytopathologist. RESULTS: There were no significant
      differences in technical success (100 vs. 100%, p = 1.000), the mean number of
      needle passes (7.0 +/- 1.6 vs. 6.8 +/- 1.5, p = 0.556), needle malfunction (0 vs.
      1.8%, p = 1.000), or complications (1.8 vs. 0%, p = 1.000) between the S+ and S-
      groups. Both groups exhibited comparable outcomes with respect to cytological
      diagnostic accuracy (93.0 vs. 91.2%, p = 1.000) and histological diagnostic
      accuracy (86.0 vs. 87.7%, p = 1.000) for malignancy. The procedure time was
      significantly shorter in the S- group than in the S+ group (32.4 +/- 11.7 vs.
      39.7 +/- 8.6 min, p < 0.001). CONCLUSIONS: EUS-guided tissue acquisition using a
      25-gauge core biopsy needle without a stylet did not decrease the diagnostic
      yield for malignancy and was associated with a shorter procedure time than that
      associated with a stylet.

PMID- 29572630
TI  - Effect of premedication on lesion detection rate and visualization of the mucosa
      during upper gastrointestinal endoscopy: a multicenter large sample randomized
      controlled double-blind study.
AB  - BACKGROUND: Premedication in upper gastrointestinal endoscopy for higher lesions
      detection rate has not been well studied so far. This study aimed to confirm
      whether premedication could improve the detection rate of early cancer or
      precancerous lesions and mucosal visibility. METHOD: From July 2015 to December
      2015, 7200 participants from 6 centers were screened by endoscopy with one of the
      4 following premedications randomly: (1) water (group D); (2) pronase (group A);
      (3) simethicone (group B); (4) pronase and simethicone (group C). Early cancer
      and precancerous lesions detection rates were taken as the primary endpoints, and
      mucosal visibility was taken as the secondary endpoint. They were compared among
      four groups to determine different premedication effects in terms of different
      anatomical sites. Trial was registered at Chinese Clinical Trial Registry; the
      registration number is ChiCTR-IOR-17010985. RESULTS: The upper gastrointestinal
      overall precancerous lesion detection rates among four groups were 8.7, 8.4,
      10.0, and 10.3%, the overall early cancer detection rates were 1.3, 1.4%, 1.5,
      and 1.6%, both without significant difference (p = 0.138 and 0.878). However, the
      visibility score distributions between control group (D) and premedication groups
      (A, B, and C) were all statistically significant, with all anatomical sites p
      values < 0.001. Subgroup analyses, from 2 centers without screening before, also
      showed significant difference in esophageal (3.9, 3.3, 4.5, and 8.4% with p =
      0.004) and overall (7.0, 5.5, 7.3, and 12.0% with p = 0.004) precancerous lesion
      detection rate. CONCLUSIONS: Premedication with pronase and simethicone may not
      increase lesion detection rates but could significantly increase the upper
      gastrointestinal mucosal visibility.

PMID- 29572631
TI  - Caste-Specific Expression of Na+/K+-ATPase in the Asian Weaver Ant, Oecophylla
      smaragdina (Fabricius, 1775).
AB  - Social insect colonies adopt different levels of survival strategies and exhibit
      well-defined reproductive division of labour. Oecophylla smaragdina (Fabricius,
      1775) has physiological and behavioral adaptations that enable them to forage at
      extreme environmental conditions and are lethal to most other insects. Ion
      homeostasis is the key process in an organism's survival mechanism. Among ion
      pumps, the ATP-dependent sodium-potassium ion pump is essential for maintaining
      the Na+ and K+ ionic balance and is well known as the primary consumer of energy.
      Oecophylla smaragdina plays pivotal role as a model among social insects for
      understanding ion homeostasis at the organization level of the castes. We have
      evaluated the expression and activity of Na+/K+-ATPase among various castes of O.
      smaragdina (worker subcastes, queen and male). Real-time PCR and immunoblotting
      analyses revealed the differential expression of Na+/K+-ATPase in the castes.
      Significantly higher expression of Na+/K+-ATPase mRNA and protein were observed
      in the minor workers, queen, major workers and males respectively. These results
      suggest that in the weaver ant colony, the castes might have variously adapted
      and evolved with a well-developed ion transport mechanism which allows them to
      perform allocated tasks within the nest and could be a key to their adaptive
      benefits towards division of labour.

PMID- 29572632
TI  - Assessment of the Insecticidal Potential of the Eupatorium buniifolium Essential
      Oil Against Triatoma infestans (Hemiptera: Reduviidae). A Chiral Recognition
      Approach.
AB  - In this research, bioactivities toward the Chagas' disease vector Triatoma
      infestans (Klug) (Hemiptera: Reduviidae) by the essential oil (EO) of Eupatorium
      buniifolium H. et A. (Asteraceae) are reported. The tests were designed in order
      to determine ovicidal activity as well as the response to vapor exposure
      (fumigant) and to topical application (contact toxicity) and as repellent. In the
      last three bioassays, nymphs from the 3rd and 4th instar were used. The assayed
      materials were obtained from aerial parts of plants collected during the months
      of March and December, throughout 4 years, in two locations. The EO samples were
      subjected to a qualitative analysis by GC-MS and the relative area of each
      component was reported by GC-FID. The main monoterpene detected was alpha-pinene
      and by using a chiral column through GC-MS experiments and having both
      stereoisomers as standards, we were able to determine that the enantiomer present
      was S,S-(-)-alpha-pinene. Although usually in studies of EOs changes in chemical
      composition are often observed due to the time of collection and the environment
      where the plant develops, in our case the differences were, with some exception,
      only at the level of the minor components. The best results were obtained in the
      experiments to determine ovicidal activity, fumigant action, and repellency. No
      worthy response was found as insecticide in the trials designed for contact
      toxicity. The results of the studied bioactivities were independent of the
      location, month, and year of collection of the plant material. This behavior
      provides an interesting scope in relation to the potential use of this natural
      blend for the control of this insect at the nymph stage as repellent as well as
      for decreasing the population by ovicidal effect. Notably, in the course of the
      two-choice repellency test, it was possible to demonstrate recognition of one of
      the enantiomers of the alpha-pinene, giving rise to a non-common
      chirality/response effect. In this assay, the levorotatory isomer was the most
      active as repellent. Considering the abundance of the wild plant under study and
      the fact that its EO is easy to obtain, it is suggested that it could be an
      adequate natural resource to control this vector in a sustainable way as a
      complementary approach to conventional methods.

PMID- 29572633
TI  - Discovery of bioactive compounds.

PMID- 29572634
TI  - Non-invasive radiomics approach potentially predicts non-functioning pituitary
      adenomas subtypes before surgery.
AB  - PURPOSE: To make individualised preoperative prediction of non-functioning
      pituitary adenoma (NFPAs) subtypes between null cell adenomas (NCAs) and other
      subtypes using a radiomics approach. METHODS: We enrolled 112 patients (training
      set: n = 75; test set: n = 37) with complete T1-weighted magnetic resonance
      imaging (MRI) and contrast-enhanced T1-weighted MRI (CE-T1). A total of 1482
      quantitative imaging features were extracted from T1 and CE-T1 images. Support
      vector machine trained a predictive model that was validated using a receiver
      operating characteristics (ROC) analysis on an independent test set. Moreover, a
      nomogram was constructed incorporating clinical characteristics and the radiomics
      signature for individual prediction. RESULTS: T1 image features yielded area
      under the curve (AUC) values of 0.8314 and 0.8042 for the training and test sets,
      respectively, while CE-T1 image features provided no additional contribution to
      the predictive model. The nomogram incorporating sex and the T1 radiomics
      signature yielded good calibration in the training and test sets (concordance
      index (CI) = 0.854 and 0.857, respectively). CONCLUSION: This study focused on
      the preoperative prediction of NFPA subtypes between NCAs and others using a
      radiomics approach. The developed model yielded good performance, indicating that
      radiomics had good potential for the preoperative diagnosis of NFPAs. KEY POINTS:
      * MRI may help in the pre-operative diagnosis of NFPAs subtypes * Retrospective
      study showed T1-weighted MRI more useful than CE-T1 in NCAs diagnosis * Treatment
      decision making becomes more individualised * Radiomics approach had potential
      for classification of NFPAs.

PMID- 29572635
TI  - Automated estimation of image quality for coronary computed tomographic
      angiography using machine learning.
AB  - OBJECTIVES: Our goal was to evaluate the efficacy of a fully automated method for
      assessing the image quality (IQ) of coronary computed tomography angiography
      (CCTA). METHODS: The machine learning method was trained using 75 CCTA studies by
      mapping features (noise, contrast, misregistration scores, and un
      interpretability index) to an IQ score based on manual ground truth data. The
      automated method was validated on a set of 50 CCTA studies and subsequently
      tested on a new set of 172 CCTA studies against visual IQ scores on a 5-point
      Likert scale. RESULTS: The area under the curve in the validation set was 0.96.
      In the 172 CCTA studies, our method yielded a Cohen's kappa statistic for the
      agreement between automated and visual IQ assessment of 0.67 (p < 0.01). In the
      group where good to excellent (n = 163), fair (n = 6), and poor visual IQ scores
      (n = 3) were graded, 155, 5, and 2 of the patients received an automated IQ score
      > 50 %, respectively. CONCLUSION: Fully automated assessment of the IQ of CCTA
      data sets by machine learning was reproducible and provided similar results
      compared with visual analysis within the limits of inter-operator variability.
      KEY POINTS: * The proposed method enables automated and reproducible image
      quality assessment. * Machine learning and visual assessments yielded comparable
      estimates of image quality. * Automated assessment potentially allows for more
      standardised image quality. * Image quality assessment enables standardization of
      clinical trial results across different datasets.

PMID- 29572636
TI  - Apparent diffusion coefficient for molecular subtyping of non-gadolinium
      enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional
      region of interest analysis.
AB  - OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC)
      measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas,
      comparing whole tumour against single slice analysis. METHODS: Volumetric T2
      derived masks of 44 gliomas were co-registered to ADC maps with ADC mean
      (ADCmean) calculated. For the slice analysis, two observers placed regions of
      interest in the largest tumour cross-section. The ratio (ADCratio) between
      ADCmean in the tumour and normal appearing white matter was calculated for both
      methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the
      lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact
      group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p <
      0.01). A volumetric ADCmean threshold of 1201 * 10-6 mm2/s identified IDH wild
      type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio
      cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92%
      (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1
      (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of
      91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was
      excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of
      glioma subtypes. Volumetric and two-dimensional measurements yielded similar
      results in this study. KEY POINTS: * Diffusion-weighted MRI aids the
      identification of non-gadolinium-enhancing malignant gliomas * ADC measurements
      may permit non-gadolinium-enhancing glioma molecular subtyping * IDH wild-type
      gliomas have lower ADC values than IDH-mutant tumours * Single cross-section and
      volumetric ADC measurements yielded comparable results in this study.

PMID- 29572638
TI  - Clinical outcomes following arthroscopic treatment of femoro-acetabular
      impingement using a minimal traction approach and an initial capsulotomy. Minimum
      two year follow-up.
AB  - PURPOSE: Although the arthroscopic management of femoroacetabular impingement
      (FAI) is increasing, severe complications have been reported due to traction. We
      developed an arthroscopic technique based on an initial capsulotomy and a minimal
      traction approach. The main purpose of this study was to analyze the clinical
      outcomes of FAI treatment using this technique after at least two years of follow
      up. METHODS: Forty-seven consecutive patients underwent surgery for FAI. There
      were two initial portals: a proximal anterolateral portal and a distal anterior
      instrumental portal. An anterior working space was created and a T-shaped
      incision was made in the anterior capsule to relieve joint distraction. Short
      traction (less than 20 mn) made it possible to approach the central compartment.
      Acetabuloplasty was performed in the presence of pincer impingement. Traction was
      then released. A head-neck femoral osteochondroplasty was performed in case of
      bump impingement. All patients underwent a mean 3.3 +/- one years of follow-up
      based on two self-administered questionnaires: the Harris hip score and the QOL
      Oxford score. None of the patients were lost to follow-up. RESULTS: There were
      three complications: two ossifications and one case of injury to the femoral
      cutaneous nerve with good clinical outcomes at the final follow-up. Five patients
      (10%) underwent surgical revision after a mean 1.4 years of follow-up: three
      total hip arthroplasties, one peri-acetabular osteotomy, and one repeat
      arthroscopic hip debridement. The Harris score increased significantly from 60 +/
      10 to 86 +/- 15 (p < 0.0001) and the Oxford score improved from 34 +/- 15 to 50
      +/- 11. Only 25% of patients had a "forgotten hip" at the final follow-up.
      CONCLUSION: Our clinical results were comparable to previously reported outcomes
      with other surgical techniques for the management of FAI. However, it should also
      be noted that despite these good clinical outcomes, the percentage of patients
      with a "forgotten hip" is low, and patients should be informed of this.

PMID- 29572637
TI  - Observer variability of reference tissue selection for relativecerebral blood
      volume measurements in glioma patients.
AB  - OBJECTIVES: To assess observer variability of different reference tissues used
      for relative CBV (rCBV) measurements in DSC-MRI of glioma patients. METHODS: In
      this retrospective study, three observers measured rCBV in DSC-MR images of 44
      glioma patients on two occasions. rCBV is calculated by the CBV in the tumour
      hotspot/the CBV of a reference tissue at the contralateral side for
      normalization. One observer annotated the tumour hotspot that was kept constant
      for all measurements. All observers annotated eight reference tissues of normal
      white and grey matter. Observer variability was evaluated using the intraclass
      correlation coefficient (ICC), coefficient of variation (CV) and Bland-Altman
      analyses. RESULTS: For intra-observer, the ICC ranged from 0.50-0.97 (fair
      excellent) for all reference tissues. The CV ranged from 5.1-22.1 % for all
      reference tissues and observers. For inter-observer, the ICC for all pairwise
      observer combinations ranged from 0.44-0.92 (poor-excellent). The CV ranged from
      8.1-31.1 %. Centrum semiovale was the only reference tissue that showed excellent
      intra- and inter-observer agreement (ICC>0.85) and lowest CVs (<12.5 %). Bland
      Altman analyses showed that mean differences for centrum semiovale were close to
      zero. CONCLUSION: Selecting contralateral centrum semiovale as reference tissue
      for rCBV provides the lowest observer variability. KEY POINTS: * Reference tissue
      selection for rCBV measurements adds variability to rCBV measurements. * rCBV
      measurements vary depending on the choice of reference tissue. * Observer
      variability of reference tissue selection varies between poor and excellent. *
      Centrum semiovale as reference tissue for rCBV provides the lowest observer
      variability.

PMID- 29572639
TI  - Can patients manage toileting after reverse total shoulder arthroplasty? A
      systematic review.
AB  - PURPOSE: A major concern for patients undergoing reverse total shoulder
      arthroplasty (RTSA) is managing toileting after surgery. The goals of this
      systematic review of RTSA studies were to determine the following: (1) the
      percentage of patients who can manage toileting, (2) their degree of difficulty
      with toileting, and (3) the percentage of patients who can manage toileting after
      bilateral versus unilateral RTSA. METHODS: Medline, EMBASE, Google Scholar, and
      the Cochrane Central Register of Controlled Trials were searched for studies
      reporting the ability to manage toileting after RTSA. Six studies with at least
      12 months of follow-up were included, yielding 183 patients (105 unilateral RTSA,
      78 bilateral RTSA). We pooled patient data and calculated the weighted mean
      proportion of patients able to manage toileting, those who reported difficulty,
      and those able to manage toileting after unilateral versus bilateral RTSA.
      Statistical significance was set at P < 0.05. RESULTS: Most patients (92%; 95%
      confidence interval, 87-95%) were able to manage toileting after RTSA. Some
      degree of difficulty with toileting was reported for 20% of all shoulders. Almost
      all patients with bilateral RTSA were able to manage toileting with at least one
      arm (weighted mean proportion 97%; 95% confidence interval, 88-99%). There was no
      significant difference in the proportion of patients able to manage toileting
      after unilateral versus bilateral RTSA (P = 0.08). Only 3% of all papers
      published on the clinical results of RTSA by June 2017 reported upon toileting
      after the procedure. CONCLUSIONS: With the available evidence, most patients were
      able to manage toileting after RTSA, although one-fifth reported some degree of
      difficulty. Ability to manage toileting was similar after unilateral versus
      bilateral RTSA. In the future, this variable should be a standard question after
      shoulder arthroplasty. LEVEL OF EVIDENCE: IV.

PMID- 29572641
TI  - Chronic Essex-Lopresti injury: a systematic review of current treatment options.
AB  - INTRODUCTION: Essex-Lopresti lesion (ELL) is a severe injury. Most of ELL is
      recognized in chronic phase representing a therapeutic challenge for orthopaedic
      surgeons. The aim of this systematic review is to highlight and criticize current
      concepts in the surgical treatment. MATERIALS AND METHODS: The search was
      conducted according to the Preferred Reporting Items for Systematic reviews and
      Meta-Analyses (PRISMA) guideline. A comprehensive research of Pubmed database was
      made using the following Mesh term: ((Essex-Lopresti injury) OR (Essex Lopresti)
      OR (distal radio ulnar dissociation) OR (distal radio ulnar dislocation) OR
      (longitudinal forearm instability)). Quality assessment of each article was
      performed according to Coleman score by two authors. RESULTS: Eight full articles
      were included to the systematic review. Surgical treatment was differentiated in
      five categories according to the most common procedure reported in clinical
      series. The mean Coleman Score was 51.13 +/- 9.76. DISCUSSION: Case series
      reported in the literature include a limited number of patients with chronic ELL.
      Currently, salvage procedure devoted to treat a wrong diagnosis and an incorrect
      treatment is used. Radial head replacement together with ulnar shortening
      osteotomy and interosseous membrane reconstruction are the most common treatments
      of choice, but at present, there is not yet a shared scheme of management for
      patients with chronic ELL. CONCLUSIONS: According to current literature, a case
      by-case treatment must always be considered. Further investigations, with higher
      level of evidence, quality of study design, and number of patients, are needed to
      better assess clinical results and complication of each technique. LEVEL OF
      EVIDENCE: IV.

PMID- 29572640
TI  - Quality of life of patients with osteonecrosis of the femoral head: a multicentre
      study.
AB  - PURPOSE: Quality-of-life (QOL) assessments in patients with osteonecrosis of the
      femoral head (ONFH) have rarely been reported. This multicentre study aimed to
      elucidate the relationship between disease severity, including necrotic lesion
      type and radiological staging, and QOL, as well as between patients'
      characteristics and QOL. METHODS: Two hundred seventy-four patients with ONFH
      (108 females, 166 males; median age, 46 years) were asked to complete self
      assessment QOL questionnaires including the Japanese Orthopaedic Association Hip
      Disease Evaluation Questionnaire, Oxford Hip Score, and SF-12v2. RESULTS:
      Patients with large necrotic lesion type or collapsed ONFH had low QOL scores.
      Among patients with non-collapsed lesions, patients with alcohol-associated ONFH
      had lower QOL scores than those with steroid-associated ONFH, those with
      bilateral ONFH had lower mental scores, and male patients had worse social
      condition scores. Among patients with collapsed lesions, middle-aged patients
      exhibited lower mental QOL, and a strong correlation was observed between social
      activity and mental health. CONCLUSION: Collapsed ONFH was associated with low
      QOL scores. Among patients with non-collapsed lesions, alcohol-associated ONFH,
      bilateral disease, and male sex were linked to low QOL scores.

PMID- 29572642
TI  - [Pancreaticojejunostomy: duct-to-mucosa anastomosis or invagination anastomosis?]

PMID- 29572643
TI  - Novel Mapping Strategies for Ventricular Tachycardia Ablation.
AB  - Despite advances in antiarrhythmic and device therapy, ventricular tachycardia
      (VT) continues to be a major cause of increased morbidity and mortality. During
      scar-mediated monomorphic ventricular tachycardia ablation, the search for
      critical isthmus sites continues to be the primary goal during successful
      ablative procedures. However, given the overwhelming hemodynamic instability of
      most ventricular arrhythmias (> 70%), VT ablation is increasingly performed
      during sinus rhythm. This technique requires either a greater reliance on isthmus
      surrogates, or more extensive ablation techniques and is a more probabilistic
      approach to substrate modification. We believe that a better understanding of
      scar physiology and activation during sinus rhythm has important implications for
      clinical workflow and mechanistic improvements with current ablation strategies.
      With advancements in high-density mapping and multi-electrode catheter
      technology, mapping of VT substrates is performed with higher resolution, with
      improved visualization of local abnormal ventricular activities (LAVA), and with
      a more nuanced functional understanding of late potentials. As a prerequisite,
      our practice for VT ablation starts with a high-density structural map to
      identify voltage abnormalities as well as an isochronal functional map of sinus
      rhythm activation to identify region of discontinuous wavefront propagation. As
      the era of increased automation has emerged, there continues to be vast array of
      customizable features, and we have adopted the use of multiple wavefront mapping
      to further elucidate possible arrhythmogenic substrate. Our emerging
      understanding of how scar propagation patterns relate to areas of abnormal
      signals and critical isthmuses may greatly improve the ability to identify
      surrogates during sinus rhythm and help localize the most arrhythmogenic regions
      within a given scar. In the hemodynamically unstable patients, we routinely
      integrate isochronal late activation mapping (ILAM) to identify areas of slow
      conduction to initiate our targeted ablation and substrate modification. Multi
      electrode delineation of the entire reentrant VT circuit has value in
      understanding the size of the circuit, rotational nature, and transmural extent
      of human reentry. Correlative studies between the activation of the complete VT
      circuit and sinus rhythm are likely to provide important mechanistic insights on
      where fixed and/or functional block occurs within a complex scar substrate.

PMID- 29572644
TI  - Expression of a Constitutively Active Human Insulin Receptor in Hippocampal
      Neurons Does Not Alter VGCC Currents.
AB  - Memory and cognitive decline are the product of numerous physiological changes
      within the aging brain. Multiple theories have focused on the oxidative, calcium,
      cholinergic, vascular, and inflammation hypotheses of brain aging, with recent
      evidence suggesting that reductions in insulin signaling may also contribute.
      Specifically, a reduction in insulin receptor density and mRNA levels has been
      implicated, however, overcoming these changes remains a challenge. While
      increasing insulin receptor occupation has been successful in offsetting
      cognitive decline, alternative molecular approaches should be considered as they
      could bypass the need for brain insulin delivery. Moreover, this approach may be
      favorable to test the impact of continued insulin receptor signaling on neuronal
      function. Here we used hippocampal cultures infected with lentivirus with or
      without IRbeta, a constitutively active, truncated form of the human insulin
      receptor, to characterize the impact continued insulin receptor signaling on
      voltage-gated calcium channels. Infected cultures were harvested between DIV 13
      and 17 (48 h after infection) for Western blot analysis on pAKT and AKT. These
      results were complemented with whole-cell patch-clamp recordings of individual
      pyramidal neurons starting 96 h post-infection. Results indicate that while a
      significant increase in neuronal pAKT/AKT ratio was seen at the time point
      tested, effects on voltage-gated calcium channels were not detected. These
      results suggest that there is a significant difference between constitutively
      active insulin receptors and the actions of insulin on an intact receptor,
      highlighting potential alternate mechanisms of neuronal insulin resistance and
      mode of activation.

PMID- 29572646
TI  - Knockout of Amyloid beta Protein Precursor (APP) Expression Alters
      Synaptogenesis, Neurite Branching and Axonal Morphology of Hippocampal Neurons.
AB  - The function of the beta-A4 amyloid protein precursor (APP) of Alzheimer's
      disease (AD) remains unclear. APP has a number of putative roles in neuronal
      differentiation, survival, synaptogenesis and cell adhesion. In this study, we
      examined the development of axons, dendrites and synapses in cultures of
      hippocampus neutrons derived from APP knockout (KO) mice. We report that loss of
      APP function reduces the branching of cultured hippocampal neurons, resulting in
      reduced synapse formation. Using a compartmentalised culture approach, we found
      reduced axonal outgrowth in cultured hippocampal neurons and we also identified
      abnormal growth characteristics of isolated hippocampal neuron axons. Although
      APP has previously been suggested to play an important role in promoting cell
      adhesion, we surprisingly found that APPKO hippocampal neurons adhered more
      strongly to a poly-L-lysine substrate and their neurites displayed an increased
      density of focal adhesion puncta. The findings suggest that the function of APP
      has an important role in both dendritic and axonal growth and that endogenous APP
      may regulate substrate adhesion of hippocampal neurons. The results may explain
      neuronal and synaptic morphological abnormalities in APPKO mice and the presence
      of abnormal APP expression in dystrophic neurites around amyloid deposits in AD.

PMID- 29572645
TI  - Effects of the Serotonin 5-HT1A Receptor Biased Agonists, F13714 and F15599, on
      Striatal Neurotransmitter Levels Following L-DOPA Administration in Hemi
      Parkinsonian Rats.
AB  - Peak-dose dyskinesia is associated with the dramatic increase in striatal
      dopamine levels that follows L-DOPA administration. The 'false neurotransmitter'
      hypothesis postulates that the latter is likely due to an aberrant processing of
      L-DOPA by serotonergic neurons. In keeping with this hypothesis, two highly
      selective 'biased agonists' of 5-HT1A receptors-namely F13714 and F15599 (NLX
      101)-were recently shown to exhibit exceptionally potent anti-dyskinetic activity
      without impairing L-DOPA therapeutic properties despite their differential
      targeting of 5-HT1A receptor sub-populations. In this study, we investigated
      whether these two compounds dampened peak L-DOPA-induced dopamine microdialysate
      levels in the striatum of hemi-parkinsonian rats. Acute administration of either
      F13714 (0.04 and 0.16 mg/kg i.p.) or F15599 (0.16 and 0.64 mg/kg, i.p.) blunted L
      DOPA (2 mg/kg)-induced increases in dopamine microdialysate levels in the
      denervated striatum (following unilateral injection of 6-OHDA into the medial
      forebrain bundle). No significant changes were observed on the intact side of the
      brain. Concurrently, both drugs profoundly reduced striatal serotonin levels on
      both sides of the brain. In addition, F13714 and F15599, in the presence of L
      DOPA, produced a dose-dependent increase in glutamate levels, but this effect was
      restricted to later time points. These finding support the interpretation that
      F13714 and F15599 mediate their anti-dyskinetic effects by blunting of the peak
      in dopamine levels via activation of somatodendritic serotonin 5-HT1A receptors
      and the consequent inhibition of serotonergic neurons. This study adds to the
      growing body of evidence supporting the development of a potent 5-HT1A receptor
      agonist for treatment of peak-dose dyskinesia.

PMID- 29572647
TI  - Neuroblastoma: clinical and biological approach to risk stratification and
      treatment.
AB  - Neuroblastoma is the most common extra-cranial solid tumor of childhood and the
      most common in the first year of life. It is a unique malignancy in that infants
      often present with either localized or metastatic disease that can spontaneously
      regress without intervention while older children can succumb to the disease
      after months to years of arduous therapy. Given this wide range of outcomes, the
      International Neuroblastoma Risk Group was created to stratify patients based on
      presenting characteristics and tumor biology in order to guide intensity of
      treatment strategies. The goal has been to decrease therapy for low-risk patients
      to avoid long-term complications while augmenting and targeting therapies for
      high-risk patients to improve overall survival. The international risk
      stratification depends on age, stage, histology, MYCN gene amplification status,
      tumor cell ploidy and segmental chromosomal abnormalities. Treatment for
      asymptomatic low-risk patients with an estimated survival of > 98% is often
      observation or surgical resection alone, whereas intermediate-risk patients with
      an estimated survival of > 90% require moderate doses of response-adjusted
      chemotherapy along with resection. High-risk patients undergo multiple cycles of
      combination chemotherapy before surgery, followed by consolidation with
      myeloablative autologous hematopoietic stem cell transplantation and local
      radiation and finally immunotherapy with differentiation therapy as maintenance
      phase. With this approach, outcome for patients with neuroblastoma has improved,
      as the field continues to expand efforts in more targeted therapies for high-risk
      patients.

PMID- 29572648
TI  - The approach of visual stimuli influences expectations about stimulus types for
      subsequent somatosensory stimuli.
AB  - It is known that perceiving a visual stimulus influences the processing of
      subsequent somatosensory stimuli. In particular, an emotion-laden visual stimulus
      influences the processing of types of subsequent somatosensory stimuli.
      Additionally, visual stimuli approaching the body facilitate spatial and temporal
      expectations about subsequent somatosensory stimuli even if the visual stimuli do
      not contain emotional information; however, it remains unclear whether the
      approach of non-emotional visual stimuli also influences such expectations. To
      investigate whether the approach of non-emotional visual stimuli influences
      expectations about types of subsequent somatosensory stimuli, event-related brain
      potentials (ERPs) during a simple reaction time task using somatosensory stimuli
      were recorded. Specific colors of visual stimuli and types of somatosensory
      stimuli were combined to form congruent and incongruent trials. In the congruent
      trials, specific combinations (e.g., blue color and a single pulse) were
      presented (80% of the trials), whereas in the incongruent trials, different
      combinations (e.g., blue color and a train pulse) were presented (20% of the
      trials). Under the approach condition, the visual stimuli sequentially approached
      the wrist to which the somatosensory stimulus was presented. In the neutral
      condition, the visual stimuli did not approach. The results of the ERP analysis
      showed that incongruence evoked a P3 response with larger amplitude under the
      approach condition than under the neutral condition. This result suggests that
      visual stimuli that approach the body function as clues regarding the types of
      subsequent somatosensory stimuli even if the visual stimuli do not contain
      emotional information.

PMID- 29572649
TI  - Postural responses to target jumps and background motion in a fast pointing task.
AB  - When reaching towards an object while standing, one's hand responds very quickly
      to visual perturbations such as the target being displaced or the background
      moving. Such responses require postural adjustments. When the background moves,
      its motion might be attributed to self-motion in a stable world, and thereby
      induce compensatory postural adjustments that affect the hand. The changes in
      posture associated with a given hand movement response may, therefore, be
      different for the two types of perturbations. To see whether they are, we asked
      standing participants to move their hand in the sagittal direction away from
      their body to targets displayed on a horizontal screen in front of them. The
      target displacements and background motion were in the lateral direction. We
      found hand movement responses that were in line with earlier reports, with a
      latency that was slightly shorter for target displacements than for background
      motion, and that was independent of target displacement size or background motion
      speed. The trunk responded to both perturbations with a modest lateral sway. The
      two main findings were that the upper trunk responded even before the hand did so
      and that the head responded to background motion but hardly responded to target
      displacements. These findings suggest that postural adjustments associated with
      adjusting the hand movement precede the actual adjustments to the movement of the
      hand, while at the same time, participants try to keep their head stable on the
      basis of visual information.

PMID- 29572650
TI  - Increased enslaving in elderly is associated with changes in neural control of
      the extrinsic finger muscles.
AB  - Aging has consequences for hand motor control, among others affecting finger
      force enslaving during static pressing tasks. The aim of this study was to assess
      whether the extent of finger force enslaving changes with aging during a task
      that involves both static and dynamic phases. Ten right-handed young (22-30
      years) and ten elderly subjects (67-79 years) were instructed to first exert a
      constant force (static phase) and then flex their index finger while
      counteracting constant resistance forces orthogonal to their fingertips (dynamic
      phase). The other fingers (non-instructed) were held in extension. EMG activities
      of the flexor digitorum superficialis (FDS) and extensor digitorum (ED) muscles
      in the regions corresponding to the index, middle and ring fingers together with
      their forces and position of index finger were measured. In both elderly and
      young, forces exerted by the non-instructed fingers increased (around 0.6 N for
      both young and elderly) during isotonic flexion of the index finger, but with a
      different delay of on average 100 +/- 72 ms in elderly and 334 +/- 101 ms in
      young subjects. Results also suggest different responses in activity of FDS and
      ED muscle regions of the non-instructed fingers to index finger flexion between
      elderly and young subjects. The enslaving effect was significantly higher in
      elderly than in young subjects both in the static (12% more) and dynamic (14%
      more) phases. These differences in enslaving can at least partly be explained by
      changes in neuromuscular control.

PMID- 29572651
TI  - Diazepam blocks 50 kHz ultrasonic vocalizations and stereotypies but not the
      increase in locomotor activity induced in rats by amphetamine.
AB  - RATIONALE: We have recently shown that the benzodiazepine diazepam inhibits
      dopamine release in the NAc and blocks the increased release of dopamine induced
      by DL-amphetamine. Rewarding stimuli and many drugs of abuse can induce dopamine
      release in the nucleus accumbens as well as 50-kHz ultrasonic vocalizations
      (USVs) in rats. OBJECTIVES: In the present study, we tested the hypothesis that
      diazepam can also block the increase in locomotor activity and USVs elicited by
      amphetamine. METHODS: Fifty-kilohertz USVs, stereotypy, and locomotor behavior
      were scored in adult male Wistar rats treated with i.p. injections of saline, 3
      mg/kg DL-amphetamine, 2 mg/kg diazepam, 0.2 mg/kg haloperidol, or a combination
      of these drugs. RESULTS: In agreement with previous studies, amphetamine caused
      significant increases in the number of USV calls, stereotypies, and locomotor
      activity. The D2 dopamine receptor antagonist haloperidol blocked the effects of
      amphetamine on USVs, stereotypy, and locomotor activity. Diazepam blocked the
      effect of amphetamine on USV and stereotypy, but not on horizontal locomotion.
      CONCLUSIONS: These results suggest that diazepam blocks the rewarding effect of
      amphetamine. This finding is promising for basic research regarding treatments of
      substance use disorders and evaluation of the impact of benzodiazepines on
      motivation.

PMID- 29572652
TI  - Differential regulation of alcohol taking and seeking by antagonism at
      alpha4beta2 and alpha3beta4 nAChRs.
AB  - RATIONALE: Alcoholism is a serious public health problem throughout the world.
      Current pharmacotherapies for the treatment of this disorder are poorly
      effective. Preclinical and clinical findings point to nicotinic acetylcholine
      receptors (nAChRs) as a promising target for the development of novel and
      effective medications. Assuage Pharmaceuticals, in collaboration with Torrey
      Pines Institute for Molecular Studies, has discovered a new class of potent and
      selective alpha4beta2 nAChR antagonists. OBJECTIVE: Here, it was hypothesized
      that alpha4beta2 nAChR antagonism is a viable approach for treatment of alcohol
      use disorders. RESULTS: When tested in rats, one lead compound, AP-202,
      attenuated both operant alcohol and nicotine self-administration in a paradigm in
      which the two reinforcers were concurrently available. The conotoxin TP2212-59, a
      selective alpha3beta4 nAChR antagonist, was only effective in reducing nicotine
      self-administration. AP-202 also reduced alcohol but not food responding when
      alcohol was presented as the only reinforcer, whereas the commercially available
      alpha4beta2 nAChR antagonist dihydro-beta-erythroidine failed to alter alcohol
      self-administration. AP-202 did not block relapse-like behavior induced by
      previously alcohol-associated stimuli or yohimbine stress. In a reinstatement
      paradigm, in which alcohol seeking was triggered by a nicotine challenge, a
      behavior successfully inhibited by the nonselective nAChR antagonist
      mecamylamine, AP-202 was not effective, while pretreatment with TP2212-59
      abolished nicotine-induced reinstatement of alcohol seeking. CONCLUSIONS: These
      findings suggest differential roles for alpha4beta2 and alpha3beta4 nAChR on
      alcohol taking and seeking with selective blockade of alpha4beta2 nAChR being
      more implicated in modulating alcohol taking while selective blockade of
      alpha3beta4 nAChR is involved in nicotine-induced alcohol seeking.

PMID- 29572654
TI  - The difference in visuomotor feedback velocity control during spiral drawing
      between Parkinson's disease and essential tremor.
AB  - In a spiral task, the accuracy of the spiral trajectory, which is affected by
      tracing or tracking ability, differs between patients with Parkinson's disease
      (PD) and essential tremor (ET). However, not many studies have analyzed velocity
      differences between the groups during this task. This study aimed to examine
      differences between the groups related to this characteristic using a tablet.
      Fourteen PD, 12 ET, and 12 control group participants performed two tasks:
      tracing a given spiral (T1) and following a guiding point (T2). A digitized
      tablet was used to record movements and trajectory. Effects of direct visual
      feedback on intergroup and intragroup velocity were measured. Although PD
      patients had a significantly lower T1 velocity than the control group (p < 0.05),
      they could match the velocity of the guiding point (3.0 cm/s) in T2. There was no
      significant difference in the average T1 velocity between ET and the control
      groups (p = 0.26); however, the T2 velocity of ET patients was significantly
      higher than the control group (p < 0.05). They were also unable to adjust the
      velocity to match the guiding point, indicating that ET patients have a poorer
      ability to follow dynamic guidance. When both groups of patients have similar
      action tremor severity, their ability to follow dynamic guidance was still
      significantly different. Our study combined visual feedback with spiral drawing
      and demonstrated differences in the following-velocity distribution in PD and ET.
      This method may be used to distinguish the tremor presentation of both diseases,
      and thus, provide accurate diagnosis.

PMID- 29572655
TI  - Correction to: Association of ischemic stroke with ankylosing spondylitis: a
      nationwide longitudinal cohort study.
AB  - The authors regret to state that an incorrect image was uploaded in Fig. 2.
      Please see a newly updated Fig. 2. All statements including Figure Legends are
      correct.

PMID- 29572653
TI  - Delta/mu opioid receptor interactions in operant conditioning assays of pain
      depressed responding and drug-induced rate suppression: assessment of therapeutic
      index in male Sprague Dawley rats.
AB  - RATIONALE AND OBJECTIVES: Although delta/mu receptor interactions vary as a
      function of behavioral endpoint, there have been no assessments of these
      interactions using assays of pain-depressed responding. This is the first report
      of delta/mu interactions using an assay of pain-depressed behavior. METHODS: A
      mult-cycle FR10 operant schedule was utilized in the presence of (nociception)
      and in the absence of (rate suppression) a lactic acid inflammatory pain-like
      manipulation. SNC80 and methadone were used as selective/high efficacy delta and
      mu agonists, respectively. Both SNC80 and methadone alone produced a dose
      dependent restoration of pain-depressed responding and dose-dependent response
      rate suppression. Three fixed ratio mixtures, based on the relative potencies of
      the drugs in the nociception assay, also produced dose-dependent antinociception
      and sedation. Isobolographic analysis indicated that all three mixtures produced
      supra-additive antinociceptive effects and simply additive sedation effects.
      CONCLUSIONS: The therapeutic index (TI) inversely varied as a function of amount
      of SNC80 in the mixture, such that lower amounts of SNC80 produced a higher TI,
      and larger amounts produced a lower TI. Compared to literature using standard
      pain-elicited assays, the orderly relationship between SNC80 and TI reported here
      may be a unique function of assessing pain-depressed behavior.

PMID- 29572656
TI  - The importance of endpoint selection: How effective does a drug need to be for
      success in a clinical trial of a possible Alzheimer's disease treatment?
AB  - To date, Alzheimer's disease (AD) clinical trials have been largely unsuccessful.
      Failures have been attributed to a number of factors including ineffective drugs,
      inadequate targets, and poor trial design, of which the choice of endpoint is
      crucial. Using data from the Alzheimer's Disease Neuroimaging Initiative, we have
      calculated the minimum detectable effect size (MDES) in change from baseline of a
      range of measures over time, and in different diagnostic groups along the AD
      development trajectory. The Functional Activities Questionnaire score had the
      smallest MDES for a single endpoint where an effect of 27% could be detected
      within 3 years in participants with Late Mild Cognitive Impairment (LMCI) at
      baseline, closely followed by the Clinical Dementia Rating Sum of Boxes (CDRSB)
      score at 28% after 2 years in the same group. Composite measures were even more
      successful than single endpoints with an MDES of 21% in 3 years. Using
      alternative cognitive, imaging, functional, or composite endpoints, and
      recruiting patients that have LMCI could improve the success rate of AD clinical
      trials.

PMID- 29572658
TI  - Evaluation of the dislocation and long-term sonographic detectability of a
      hydrogel-based breast biopsy site marker.
AB  - PURPOSE: To evaluate the usefulness of the HydroMARK, a hydrogel-based breast
      biopsy site marker for ultrasound localization of breast lesions, we investigated
      the tendency for dislocation and sonographic detectability of the marker placed
      in patients. MATERIALS AND METHODS: The marker was placed in lesions that were
      expected to become obscured after biopsy for a suspicious breast lesion or after
      neoadjuvant chemotherapy for breast cancer. The patients consented to return for
      a repeat ultrasound +/- mammography examination, and the degree of displacement
      of the marker was measured as the marker-to-residual lesion distance. RESULTS:
      The marker was placed after stereotactic biopsy, ultrasound-guided biopsy, and
      before/during neoadjuvant chemotherapy, in 11, 22, and 7 lesions, respectively.
      Surgical resection was performed for 22 of the 40 lesions, while remaining 18
      benign lesions were followed. The marker was sonographically detectable in 89.7%
      (35/39), 100% (35/35), and 100% (18/18) of the cases, respectively, at a median
      of 8 days, 13 weeks, and 11 months after the deployment. The degree of
      displacement was lower in the ultrasound-guided placement group than in the
      stereotactic placement group (median displacement: 0 vs. 4.3 mm; p = 0.001), it
      was also lower in the core-needle biopsy and neoadjuvent therapy cases than in
      the vacuum-assisted biopsy cases (p = 0.003). At a median interval of 2.5 months
      after deployment, the marker remained unchanged in location in all cases (n = 18,
      p = NS). CONCLUSIONS: The HydroMARK appears to be a safe and effective marker
      with the advantageous characteristics of a low tendency for dislocation with time
      and long-term sonographic detectability.

PMID- 29572657
TI  - A guanine insert in OsBBS1 leads to early leaf senescence and salt stress
      sensitivity in rice (Oryza sativa L.).
AB  - KEY MESSAGE: A rice receptor-like kinase gene OSBBS1/OsRLCK109 was identified;
      this gene played vital roles in leaf senescence and the salt stress response.
      Early leaf senescence can cause negative effects on rice yield, but the
      underlying molecular regulation is not fully understood. bilateral blade
      senescence 1 (bbs1), an early leaf senescence mutant with a premature senescence
      phenotype that occurs mainly performing at the leaf margins, was isolated from a
      rice mutant population generated by ethylmethane sulfonate (EMS) treatment. The
      mutant showed premature leaf senescence beginning at the tillering stage and
      exhibited severe symptoms at the late grain-filling stage. bbs1 showed
      accelerated dark-induced leaf senescence. The OsBBS1 gene was cloned by a map
      based cloning strategy, and a guanine (G) insertion was found in the first exon
      of LOC_Os03g24930. This gene encodes a receptor-like cytoplasmic kinase and was
      named OsRLCK109 in a previous study. Transgenic LOC_Os03g24930 knockout plants
      generated by a CRISPR/Cas9 strategy exhibited similar early leaf senescence
      phenotypes as did the bbs1 mutant, which confirmed that LOC_Os03g24930 was the
      OsBBS1 gene. OsBBS1/OsRLCK109 was expressed in all detected tissues and was
      predominantly expressed in the main vein region of mature leaves. The expression
      of OsBBS1 could be greatly induced by salt stress, and the bbs1 mutant exhibited
      hypersensitivity to salt stress. In conclusion, this is the first identification
      of OsRLCKs participating in leaf senescence and playing critical roles in the
      salt stress response in rice (Oryza sativa L.).

PMID- 29572659
TI  - Reduced oligodendrocyte density in layer 5 of the prefrontal cortex in
      schizophrenia.
AB  - Neuroimaging and post-mortem studies have implicated altered myelin integrity and
      oligodendrocyte abnormalities in the dysfunction of neuronal network in
      schizophrenia, including the prefrontal cortex, Brodmann area (BA) 10. Pyramidal
      neurons in layer 5 of BA10 are the important link of reciprocal frontal cortical
      basal ganglia-thalamic circuits altered in schizophrenia. Previously, we found
      ultrastructural dystrophic and degenerative alterations of oligodendrocytes in
      layer 5 of BA10 in schizophrenia. The aim of the study was to estimate the
      numerical density (Nv) of oligodendrocytes in layer 5 of BA10 in schizophrenia as
      compared to normal controls. 17 chronic schizophrenia subjects and 22 healthy
      matched controls were studied in Nissl-stained sections using optical disector
      method. Group differences were analyzed using ANCOVA followed by post hoc
      Duncan's test. The Nv of oligodendrocytes was significantly lower (- 32%, p <
      0.001) in the schizophrenia group as compared to the control group. Young
      controls (age < 50 years old) showed significantly higher Nv of oligodendrocytes
      as compared to elderly controls (age > 50 years old). Young and elderly
      schizophrenia subgroups did not differ significantly. Both control subgroups have
      significantly higher Nv of oligodendrocytes as compared to the schizophrenia
      subgroups. Decreased Nv of oligodendrocytes found in layer 5 of BA10 may be the
      result of dystrophic and destructive alterations and/or disrupted development of
      oligodendrocytes in schizophrenia.

PMID- 29572660
TI  - Surface morphology of the orbitofrontal cortex in individuals at risk of
      psychosis: a multicenter study.
AB  - Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a
      fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital
      sulcus, have been reported in schizophrenia, possibly reflecting abnormal
      neurodevelopment during gestation. However, whether high-risk subjects for
      developing psychosis also exhibit these gross morphologic anomalies is not well
      documented. This multicenter MRI study from four scanning sites in Japan
      investigated the distribution of the number of intermediate and posterior orbital
      sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk
      mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not
      (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a
      significantly lower number of intermediate and posterior orbital sulci compared
      with the controls, which was associated with prodromal symptomatology. However,
      there was no group difference in OFC pattern distribution. The ARMS-P and -NP
      groups did not differ in OFC surface morphology. These results suggest that gross
      morphology of the OFC in high-risk subjects may at least partly reflect
      neurodevelopmental pathology related to vulnerability to psychosis.

PMID- 29572661
TI  - Identification and functional analysis of the NLP-encoding genes from the
      phytopathogenic oomycete Phytophthora capsici.
AB  - Phytophthora capsici is a hemibiotrophic, phytopathogenic oomycete that infects a
      wide range of crops, resulting in significant economic losses worldwide. By means
      of a diverse arsenal of secreted effector proteins, hemibiotrophic pathogens may
      manipulate plant cell death to establish a successful infection and colonization.
      In this study, we described the analysis of the gene family encoding necrosis-
      and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) in P. capsici, and
      identified 39 real NLP genes and 26 NLP pseudogenes. Out of the 65 predicted NLP
      genes, 48 occur in groups with two or more genes, whereas the remainder appears
      to be singletons distributed randomly among the genome. Phylogenetic analysis of
      the 39 real NLPs delineated three groups. Key residues/motif important for the
      effector activities are degenerated in most NLPs, including the nlp24 peptide
      consisting of the conserved region I (11-aa immunogenic part) and conserved
      region II (the heptapeptide GHRHDWE motif) that is important for phytotoxic
      activity. Transcriptional profiling of eight selected NLP genes indicated that
      they were differentially expressed during the developmental and plant infection
      phases of P. capsici. Functional analysis of ten cloned NLPs demonstrated that
      Pc11951, Pc107869, Pc109174 and Pc118548 were capable of inducing cell death in
      the Solanaceae, including Nicotiana benthamiana and hot pepper. This study
      provides an overview of the P. capsici NLP gene family, laying a foundation for
      further elucidating the pathogenicity mechanism of this devastating pathogen.

PMID- 29572662
TI  - Clinical Pharmacokinetics of Amikacin in Pediatric Patients: A Comprehensive
      Review of Population Pharmacokinetic Analyses.
AB  - Amikacin plays a key role in the treatment of severe hospital-acquired infections
      with Gram-negative bacteria. Therapeutic use of amikacin is challenged by high
      inter-individual variability (IIV) combined with a narrow therapeutic spectrum.
      Pediatric patients represent a particularly fragile population where adequate
      dosing is crucial yet challenging to achieve due significant IIV associated with
      developmental processes and other factors. The current review provides an
      overview of parametric population pharmacokinetic analyses of amikacin in
      pediatric patients and associated patient-specific determinants of IIV. We
      searched PubMed for parametric population pharmacokinetic analyses of amikacin in
      pediatric patients. Information on patient population, study design,
      pharmacokinetic model characteristics, and identified patient-specific predictors
      of IIV was collected. Comparative analyses across studies were conducted to
      characterize quantitative differences reported for different studies and patient
      populations. Eight eligible publications were identified, of which six analyses
      involved neonates up to 3 months of age and two studies investigated older
      pediatric patients (age 2-17 years). Most commonly included covariates were
      current body weight for both clearance and volume of distribution, followed by
      age-related covariates on clearance in neonatal studies (four of six models).
      Quantitative comparisons of different models reported generally showed similar
      developmental effects in neonatal populations. The present review provides a
      comprehensive overview of parametric population pharmacokinetic studies for
      amikacin. Future studies could address the knowledge gap of patients between 3
      months and 2 years of age. Furthermore, systematic studies of additional
      potential predictors for IIV (e.g., sepsis, inflammatory markers, renal function
      biomarkers) could be of relevance to address the significant IIV remaining after
      inclusion of the most commonly identified covariates.

PMID- 29572663
TI  - The Influence of Normalization Weight in Population Pharmacokinetic Covariate
      Models.
AB  - In covariate (sub)models of population pharmacokinetic models, most covariates
      are normalized to the median value; however, for body weight, normalization to 70
      kg or 1 kg is often applied. In this article, we illustrate the impact of
      normalization weight on the precision of population clearance (CLpop) parameter
      estimates. The influence of normalization weight (70, 1 kg or median weight) on
      the precision of the CLpop estimate, expressed as relative standard error (RSE),
      was illustrated using data from a pharmacokinetic study in neonates with a median
      weight of 2.7 kg. In addition, a simulation study was performed to show the
      impact of normalization to 70 kg in pharmacokinetic studies with paediatric or
      obese patients. The RSE of the CLpop parameter estimate in the neonatal dataset
      was lowest with normalization to median weight (8.1%), compared with
      normalization to 1 kg (10.5%) or 70 kg (48.8%). Typical clearance (CL)
      predictions were independent of the normalization weight used. Simulations showed
      that the increase in RSE of the CLpop estimate with 70 kg normalization was
      highest in studies with a narrow weight range and a geometric mean weight away
      from 70 kg. When, instead of normalizing with median weight, a weight outside the
      observed range is used, the RSE of the CLpop estimate will be inflated, and
      should therefore not be used for model selection. Instead, established
      mathematical principles can be used to calculate the RSE of the typical CL (CLTV)
      at a relevant weight to evaluate the precision of CL predictions.

PMID- 29572664
TI  - Identification of Cytochrome P450-Mediated Drug-Drug Interactions at Risk in
      Cases of Gene Polymorphisms by Using a Quantitative Prediction Model.
AB  - BACKGROUND AND OBJECTIVE: The magnitude of drug-drug interactions mediated by
      cytochrome P450 (CYP) may depend on the genotype of polymorphic cytochromes. The
      objective of this study was to identify drug-drug interactions with greater
      magnitude in CYP variant groups than in extensive metabolizers. METHODS: The in
      vivo mechanistic static model was used to predict the area under the curve ratio
      of drug-drug interactions. Five cytochromes (CYP3A4/5, 2D6, 2C9, 2C19, 1A2) and
      five groups of genotypes for each polymorphic cytochrome (CYP2D6, 2C9, 2C19) were
      considered. The area under the curve ratios were calculated for all combinations
      and all genotypes for 196 substrates and 96 inhibitors. Among the strongest
      interactions (area under the curve ratio greater than 5), two levels of gene
      sensitivity of drug-drug interactions were defined: the intermediate sensitivity,
      with a three- to five-fold stronger interaction in genotype groups other than in
      extensive metabolizers, and the high sensitivity, with a more than five-fold
      stronger interaction than in genotype groups other than extensive metabolizers.
      RESULTS: A red list of 104 interactions with a sensitivity greater than 3,
      involving 13 substrates and 24 interactors was obtained. There were 59 and 45
      cases of high and intermediate sensitivity, respectively. The genotypes
      associated with a high sensitivity were CYP2D6 *3-8 *3-8 (sensitivity up to 24.3)
      and CYP2C19 *2-3*2-3 (sensitivity up to 37.8). CONCLUSIONS: A cytochrome
      polymorphism may lead to major drug-drug interactions in poor metabolizers, while
      these interactions may not be significant in extensive metabolizers. Among the
      104 cases studied, the interaction could be of ca. 30-fold larger magnitude in
      the worst case. Genotyping of the patient and/or therapeutic drug monitoring of
      the substrate should be carried out when an association mentioned in the red list
      is prescribed. The concept of gene sensitivity of drug-drug interactions appears
      promising for the development of precision medicine.

PMID- 29572665
TI  - Improved fermentation performance to produce bioethanol from Gelidium amansii
      using Pichia stipitis adapted to galactose.
AB  - This study employed a statistical method to obtain optimal hyper thermal acid
      hydrolysis conditions using Gelidium amansii (red seaweed) as a source of
      biomass. The optimal hyper thermal acid hydrolysis using G. amansii as biomass
      was determined as 12% (w/v) slurry content, 358.3 mM H2SO4, and temperature of
      142.6  degrees C for 11 min. After hyper thermal acid hydrolysis, enzymatic
      saccharification was carried out. The total monosaccharide concentration was 45.1
      g/L, 72.2% of the theoretical value of the total fermentable monosaccharides of
      62.4 g/L based on 120 g dry weight/L in the G. amansii slurry. To increase
      ethanol production, 3.8 g/L 5-hydroxymethylfurfural (HMF) in the hydrolysate was
      removed by treatment with 3.5% (w/v) activated carbon for 2 min and fermented
      with Pichia stipitis adapted to high galactose concentrations via separate
      hydrolysis and fermentation. With complete HMF removal and the use of P. stipitis
      adapted to high galactose concentrations, 22 g/L ethanol was produced (yield
      0.50). Fermentation with total HMF removal and yeast adapted to high galactose
      concentrations increased the fermentation performance and decreased the
      fermentation time from 96 to 36 h compared to traditional fermentation.

PMID- 29572666
TI  - Gambling and Sport: Implicit Association and Explicit Intention Among Underage
      Youth.
AB  - This study examined whether an implicit association existed between gambling and
      sport among underage youth in Australia, and whether this implicit association
      could shape their explicit intention to gamble. A sample of 14-17 year old
      Australian participants completed two phases of tasks, including an implicit
      association test based online experiment, and a post-experiment online survey.
      The results supported the existence of an implicit association between gambling
      and sport among the participants. This implicit association became stronger when
      they saw sport-relevant (vs. sport-irrelevant) gambling logos, or gambling
      relevant (vs. gambling-irrelevant) sport names. In addition, this implicit
      association was positively related to the amount of sport viewing, but only among
      those participants who had more favorable gambling attitudes. Lastly, gambling
      attitudes and advertising knowledge, rather than the implicit association, turned
      out to be significant predictors of the explicit intention to gamble.

PMID- 29572667
TI  - Use of Therapeutics in Pregnancy and Lactation.
AB  - This theme issue of Pharmaceutical Research is dedicated to drug research and
      therapy in pregnant and breastfeeding woman. Enthusiasm for studying drug safety
      and toxicity in these patients (and in their children) has risen over the past
      decade. Yet, the accumulation of data is slow. A combined effort of industry,
      regulators, academia and clinicians can promote the treatment of these
      populations, as discussed in detail in this issue.

PMID- 29572668
TI  - Impact of artificial lagoons on seawater quality: evidence from 7 years of
      physicochemical seawater monitoring.
AB  - Seven years (2010-2016) of data on the basic physicochemical properties of
      seawater, temperature, salinity, dissolved oxygen (DO), nutrients, chlorophyll a
      (Chl a), and hydrocarbons from two lagoons were used to evaluate the impact of
      the anthropogenic activities inside the lagoon on the water quality and to
      explore the relationship of any impact from the lagoons' design. Statistical
      analysis shows the modification in water quality inside the lagoon compared to
      the ambient seawater is particularly evident for nitrate, silicate, and Chl a.
      The modification is attributed to the extensive boat activities in the lagoons
      and the limited water exchange between the lagoons and ambient seawater. However,
      the impact to both lagoons is generally limited to inside the lagoons. The
      oligotrophic state of the two lagoons was evaluated and it was found that the
      most marked code violations were found in DIN inside both lagoons. In order to
      explore the design importance, the water exchange and overall water quality was
      compared between the two lagoons. This study highlights the importance of an
      environmental design study before the construction of any lagoon project. Proper
      design would maintain acceptable water quality inside the lagoons, critical for
      environmental health and supporting continued recreational activities.

PMID- 29572669
TI  - Good glycaemic control is associated with a better prognosis in breast cancer
      patients with type 2 diabetes mellitus.
AB  - Although diabetes mellitus (DM) is one of the risk factors associated with
      increased breast cancer (BC) mortality, the effects of glycaemic control on the
      prognosis of BC have not been thoroughly evaluated. This retrospective study
      aimed to evaluate the relationship between glycaemic control and BC prognosis and
      to determine an optimal target of glycaemic control for BC patients with
      diabetes. We included 2812 stage 0-3 BC women, of whom 145 were diabetic and were
      2667 non-diabetic. In those with diabetes, a mean haemoglobin A1C (HbA1C) < 7% (n
      = 77) was defined as well-controlled diabetes, while a mean HbA1C > 9% (n = 16)
      was defined as poorly controlled diabetes. All of the BC populations were
      followed from the date on which BC was diagnosed until 31 December 2015. Cox
      regression analysis was performed to estimate the adjusted hazards for all-cause
      mortality and BC-specific mortality. After controlling for the baseline and BC
      related confounders, the adjusted hazard ratio (HR) for all-cause mortality and
      the HR for BC-specific mortality were 3.65 (95% confidence interval [95% CI] 1.13
      11.82) and 8.37 (95% CI 1.90-36.91), respectively, for poorly controlled diabetic
      women and non-DM women. However, for the diabetic women with good glycaemic
      control, the HRs of all-cause mortality and BC-specific mortality were not
      significantly different (HR 0.91, 95% CI 0.42-1.01; HR 0.77, 95% CI 0.18-3.32,
      respectively) from those for both mortalities in non-DM patients. For moderate
      controlled diabetic women, the HRs for all-cause mortality and BC-specific
      mortality were 1.95 (95% CI 0.89-4.27) and 3.55 (95% CI 1.369-9.30),
      respectively. This pilot and retrospective cohort study reveals a relationship
      between glycaemic control and BC prognosis in diabetic women. In addition, well
      controlled HbA1C, with maintained mean HbA1C values under 7%, may be associated
      with a better progression outcome of BC.

PMID- 29572670
TI  - The impact of [68Ga]PSMA I&T PET/CT on radiotherapy planning in patients with
      prostate cancer.
AB  - PURPOSE: To determine the impact of Gallium-68-labled prostate-specific membrane
      antigen positron-emission tomography/computed tomography ([68Ga]PSMA PET/CT) on
      radiotherapy planning for primary disease, biochemical cancer relapse, and
      advanced disease of prostate cancer. METHODS: A total of 106 patients with
      prostate cancer scheduled for radiation therapy underwent 120 [68Ga]PSMA PET/CT
      scans prior to radiotherapy treatment. In 20 cases, patients underwent [68Ga]PSMA
      PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse
      after surgery (RL), and 25 cases were intended for palliative treatment of
      localized metastases (MD). We retrospectively compared the impact of [68Ga]PSMA
      PET/CT on lesion detection and treatment decision to CT alone. RESULTS:
      [68Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected
      86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases
      (46%) based on the higher detection rate of [68Ga]PSMA PET/CT: in 15% of cases
      with PT, in 43% of cases with RL, and in 44% of cases with MD. CONCLUSION:
      [68Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate
      cancer, thereby significantly impacting on radiotherapy planning for primary
      disease, biochemical cancer relapse, and advanced disease of prostate cancer.

PMID- 29572671
TI  - Electronic Health Information Exchange Opportunities for Self-management of Care:
      Responses from Older Adults With and Without Cancer History in the United States.
AB  - PURPOSE OF STUDY: Of 15.5 million US cancer survivors, 80% are >= 55 years.
      Supporting older patients in care self-management through electronic health
      information (EHI) exchange may enhance recovery. We assessed: (1) perceived
      importance of EHI access to adults >= 55 years (incl survivors) and (2) age
      related preferences for EHI exchange. RECENT FINDINGS: Older adults are one of
      the fastest-growing user groups for internet/technologies. Most older adults 55
      64 years are active internet users, and use among adults >= 65 years is growing
      quickly as baby boomers mature. Understanding EHI patient-provider exchange
      preferences may provide opportunities for older patients but also begin to
      address the future needs of other patient populations, including cancer
      survivors. We observed a "digital divide" for perceived importance of EHI access
      and EHI exchange interests. Engaging older adults (i.e., >= 75 years) to improve
      comfort/experience with technologies may support EHI use in self-management.
      Survivors may have distinct EHI needs/preferences than older adults without
      cancer history.

PMID- 29572672
TI  - Cerebrospinal Fluid Prion Disease Biomarkers in Pre-clinical and Clinical
      Naturally Occurring Scrapie.
AB  - The analysis of the cerebrospinal fluid (CSF) biomarkers in patients with
      suspected prion diseases became a useful tool in diagnostic routine. Prion
      diseases can only be identified at clinical stages when the disease already
      spread throughout the brain and massive neuronal damage occurs. Consequently, the
      accuracy of CSF tests detecting non-symptomatic patients is unknown. Here, we
      aimed to investigate the usefulness of CSF-based diagnostic tests in pre-clinical
      and clinical naturally occurring scrapie. While decreased total prion protein
      (PrP) levels and positive PrP seeding activity were already detectable at pre
      symptomatic stages, the surrogate markers of neuronal damage total tau (tau) and
      14-3-3 proteins were exclusively increased at clinical stages. The present
      findings confirm that alterations in PrP levels and conformation are primary
      events in the pathology of prion diseases preceding neuronal damage. Our work
      also supports the potential use of these tests in the screening of pre
      symptomatic scrapie and human prion disease cases.

PMID- 29572673
TI  - Laparoscopic anatomical liver resection after complex blunt liver trauma: a case
      report.
AB  - BACKGROUND: Various minimally invasive therapies are important adjuncts to
      management of hepatic injuries. However, there is a certain subset of patients
      who will benefit from liver resection, but there are no reports in the literature
      on laparoscopic anatomical liver resection for the management of complications
      after blunt liver trauma. CASE PRESENTATION: A 20-year-old male was admitted to
      the Emergency Unit of a tertiary referral center following a car accident. The
      patient was hemodynamically stable, and a radiologic workup demonstrated an
      isolated grade 3 injury of the left hemiliver. Initially, a nonoperative
      management was indicated, but during days following the injury, a high-volume
      biliary fistula complicated the clinical course. Despite percutaneous drainage,
      the development of devastating consequences of biliary peritonitis was imminent.
      A pure laparoscopic anatomical liver resection was performed. Left lateral
      sectionectomy eliminated the source of bile leak, and the surgery was completed
      with abdominal cavity lavage. Postoperative outcome was uneventful, and the
      patient was discharged on day 9 after injury and day 4 after surgery returning to
      his normal activity. CONCLUSIONS: In highly selected, hemodynamically stable
      patients with no other life-threatening concomitant injuries, laparoscopic liver
      resection in elective setting is feasible and safe for the management of
      complications after complex blunt trauma of the left liver. Extensive experience
      with hepatic surgery is needed, and surgeons should understand the increased risk
      they assume by taking on more complex surgical techniques.

PMID- 29572675
TI  - Cerebral Perforating Artery Disease : Characteristics on High-Resolution Magnetic
      Resonance Imaging.
AB  - PURPOSE: Our aims were to evaluate the feasibility of high-resolution magnetic
      resonance imaging (HR-MRI) for displaying the cerebral perforating arteries in
      normal subjects and to discuss the value of HR-MRI for detecting the causes of
      infarctions in the territory of the lenticulostriate artery (LSA). METHODS:
      Included in this study were 31 healthy subjects and 28 patients who had
      infarctions in the territory supplied by the LSA. The T1-weighted imaging (T1WI),
      T2WI, diffusion-weighted imaging (DWI), and HR-MRI, including 3-dimensional time
      of-flight magnetic resonance angiography (3D-TOF-MRA) and 3D fast spin-echo T1WI
      (namely CUBE T1 in GE Healthcare), were applied on a 3-Tesla scanner. The numbers
      and route of the perforating arteries on both sides were independently confirmed
      on HR-MRI by two physicians. The Wilcoxon test was used to compare the
      differences. RESULTS: The numbers of perforating arteries in healthy subjects
      observed on 3D-TOF-MRA were as follows: numbers of the bilateral recurrent artery
      of Heubner (RAH) ranged from 0-3 (median 1), numbers of the left LSA ranged from
      0-7 (median 3), numbers of the right LSA ranged from 0-5 (median 3), numbers of
      the bilateral anterior choroidal artery ranged from 1-2 (median 1) and the
      numbers of the bilateral thalamoperforating artery ranged from 1-2 (median 1). In
      the patients with lenticulostriate infarctions, the numbers of LSAs on the
      affected side were lower than on the opposite and ipsilateral sides in the
      healthy subjects. The results were statistically significant. An abnormality of
      the RAH may lead to a centrum semiovale infarct pattern, whereas an abnormality
      of the LSA is associated with a corona radiata infarct pattern. CONCLUSION: The
      use of HR 3D-TOF-MRA and CUBE T1 had unique advantages in displaying the tiny
      perforating arteries in vivo. Moreover, effective recognition of the associated
      cerebral perforating artery and infarct patterns may enhance our understanding of
      the mechanism of stroke in patients with lenticulostriate infarctions.

PMID- 29572674
TI  - Multi-institutional study of treatment patterns in Korean patients with WHO grade
      II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.
AB  - INTRODUCTION: We performed this study to identify the treatment patterns of
      patients with low-grade gliomas (LGG) in Korea. METHODS: A total of 555 patients
      diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions
      were included. The patients were divided into four adjuvant treatment groups:
      adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20),
      adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N
      = 266) groups. We examined differences among the groups and validated
      patient/tumor characteristics associated with the adjuvant treatments. RESULTS:
      Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients
      (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was
      performed in 200 patients (36%), subtotal resection in 153 (28%), partial
      resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most
      commonly applied as an adjuvant treatment. The use of chemotherapy with or
      without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic
      regimen was procarbazine, lomustine, and vincristine (PCV); however, the
      proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor
      characteristics related with RT were male gender, non-seizure, multiple lobes
      involvement, and non-gross total resection. Chemotherapy was associated with non
      gross total resection and non-astrocytoma. CONCLUSIONS: A preference for RT and
      increased use of temozolomide was evident in the treatment pattern of LGG. The
      extent of resection was associated with a decision to perform RT and
      chemotherapy. To establish a robust guideline for LGG, further studies including
      molecular information are needed.

PMID- 29572676
TI  - Winter cholecalciferol supplementation at 55 degrees N has little effect on
      markers of innate immune defense in healthy children aged 4-8 years: a secondary
      analysis from a randomized controlled trial.
AB  - PURPOSE: We explored the effect of winter cholecalciferol (vitamin D3)
      supplementation on innate immune markers in healthy Danish children (55 degrees
      N). METHODS: In the double-blind, placebo-controlled trial, ODIN Junior, 119
      healthy, white, 4-8 year-olds were randomized to 0 (placebo), 10 or 20 ug/day of
      vitamin D3 for 20 weeks (October-March). Cheek mucosal swabs, blood samples, and
      questionnaires on acute respiratory infections the previous month were collected
      at baseline and endpoint. Innate immune markers were measured as secondary
      outcomes including in vivo oral mucosal gene expression of calprotectin (S100A9),
      lipocalin-2 (LCN2), beta-defensin-4 (DEFB4), interleukin-8 (IL-8), viperin
      (RSAD2), and the cathelicidin-antimicrobial-peptide (CAMP); ex vivo whole-blood
      lipopolysaccharide (LPS)-induced cathelicidin, IL-8, and IL-6; and plasma
      cathelicidin, together with serum 25-hydroxyvitamin D [25(OH)D]. RESULTS: Serum
      25(OH)D was 56.7 +/- 12.3 nmol/L at baseline and 31.1 +/- 7.5, 61.8 +/- 10.6, and
      75.8 +/- 11.5 nmol/L at endpoint after placebo, 10 and 20 ug/day of vitamin D3 (P
      < 0.0001), respectively. A decreased oral mucosal S100A9 expression with placebo
      [- 18 (95% CI - 1; - 32)%] was marginally avoided with 20 ug/day [6 (- 13; 28)%]
      (P = 0.06). Likewise, a decreased LPS-induced IL-8 with placebo [- 438 (95% CI -
      693; - 184) ng/L] was marginally avoided with 20 ug/day [- 109 (- 374; 157) ng/L]
      (P = 0.07). All other immune markers and respiratory infection episodes were
      unaffected by vitamin D3 supplementation (all P > 0.11). CONCLUSIONS: Winter
      vitamin D3 supplementation of 10 ug/day did not affect innate immune markers,
      whereas 20 ug/day tended to maintain the capacity to produce a few markers in
      healthy children.

PMID- 29572678
TI  - Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.
AB  - Research into photobiomodulation reveals beneficial effects of light therapy for
      a rapidly expanding list of medical conditions and illnesses. Although it has
      become more widely accepted by the mainstream medicine, the effects and
      mechanisms of action appear to be poorly understood. The therapeutic benefits of
      photobiomodulation using low-energy red lasers extend far beyond superficial
      applications, with a well-described physics allowing an understanding of how red
      lasers of certain optimum intensities may cross the cranium. We now have a model
      for explaining potential therapeusis for applications in functional neurology
      that include stroke, traumatic brain injury, and neurodegenerative conditions in
      addition to the currently approved functions in lipolysis, in onychomycosis
      treatment, and in pain management.

PMID- 29572677
TI  - A qualitative transcriptional signature to reclassify estrogen receptor status of
      breast cancer patients.
AB  - PURPOSE: Immunohistochemistry (IHC) assessment of the estrogen receptor (ER)
      status has low consensus among pathologists. Quantitative transcriptional
      signatures are highly sensitive to the measurement variation and sample quality.
      Here, we developed a robust qualitative signature, based on within-sample
      relative expression orderings (REOs) of genes, to reclassify ER status. METHODS:
      From the gene pairs with significantly stable REOs in ER+ samples and reversely
      stable REOs in ER- samples, concordantly identified from four datasets, we
      extracted a signature to determine a sample's ER status through evaluating
      whether the REOs within the sample significantly match with the ER+ REOs or the
      ER- REOs. RESULTS: A signature with 112 gene pairs was extracted. It was
      validated through evaluating whether the reclassified ER+ or ER- patients could
      benefit from tamoxifen therapy or neoadjuvant chemotherapy. In three datasets for
      IHC-determined ER+ patients treated with post-operative tamoxifen therapy, 11.6
      12.4% patients were reclassified as ER- by the signature and, as expected, they
      had significantly worse recurrence-free survival than the ER+ patients confirmed
      by the signature. On another hand, in two datasets for IHC-determined ER-
      patients treated with neoadjuvant chemotherapy, 18.8 and 7.8% patients were
      reclassified as ER+ and, as expected, their pathological complete response rate
      was significantly lower than that of the other ER- patients confirmed by the
      signature. CONCLUSIONS: The REO-based signature can provide an objective
      assessment of ER status of breast cancer patients and effectively reduce
      misjudgments of ER status by IHC.

PMID- 29572679
TI  - Copeptin Blood Content as a Diagnostic Marker of Chronic Kidney Disease.
AB  - Plasma content of copeptin increases with the advancement of chronic kidney
      disease (CKD). The purpose of this study was to evaluate copeptin content as a
      potential marker of CKD, as a single pathology or with coexisting heart failure.
      Seventy-six patients were divided into the following groups: Group 1 (control),
      without CKD and heart failure; Group 2, CKD stage 3a; Group 3, CKD stage 3b;
      Group 4, CKD stage 4; Group 5, CKD stage 5; and Group 6, CKD stage 3b and heart
      failure. For all patients, plasma concentrations of copeptin, creatinine, urea,
      cystatin C, sodium, C-reactive protein (CRP), N-terminal prohormone of brain
      natriuretic peptide (NT-proBNP), and blood pH were assessed. We found that plasma
      content of creatinine, urea, CRP, cystatin, NT-proBNP, and copeptin increased
      with CKD progression. Heart failure in CKD patients was not the cause of an
      appreciable increase of copeptin level. Copeptin/creatinine, copeptin/cystatin C
      ratios, and especially copeptin/eGFR ratio enhanced copeptin prognostic
      sensitivity concerning renal failure in CKD, compared with copeptin alone. The
      copeptin*NT-proBNP ratio decreased along CKD progression, reaching a nadir in the
      accompanying heart failure. In contradistinction, copeptin*NT-proBNP/creatinine
      ratio increased along CKD progression, reaching a peak in the accompanying heart
      failure. We conclude that copeptin is an important marker in CKD, but not so
      concerning heart failure in the disease. A decrease in copeptin*NT-proBNP and an
      increase in copeptin*NT-proBNP/creatinine ratio are useful markers of cardiac
      function decline in CKD.

PMID- 29572680
TI  - SYNTAX Score and Outcomes of Coronary Revascularization in Diabetic Patients.
AB  - PURPOSE OF REVIEW: This review describes the dynamic relationship between
      diabetes mellitus (DM) and coronary artery disease (CAD) with respect to
      different revascularization strategies and how angiographic tools such as the
      Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score can supplement
      clinical decision-making. RECENT FINDINGS: The SYNTAX score characterizes the
      anatomical extent of CAD in terms of the number of lesions, functional
      importance, and complexity. Studies not limited to patients with DM suggest that
      percutaneous coronary intervention (PCI) is a reasonable alternative to coronary
      artery bypass grafting (CABG) in patients with low-medium SYNTAX scores, while
      patients with high SYNTAX scores should be revascularized with CABG if operable.
      Similar findings were also observed for diabetes patients with multivessel
      disease in retrospective pooled analysis. The SYNTAX II score combines anatomical
      and clinical risk to improve upon the decision regarding the optimal
      revascularization strategy. The SYNTAX II score can be applied to patients with
      DM. The SYNTAX scores provide guidance to clinicians faced with determining the
      optimal revascularization strategy in patients with DM and advanced CAD. Using a
      heart team approach, the information can be considered along with other factors
      that influence PCI or CABG risk.

PMID- 29572681
TI  - HIV and the Macrophage: From Cell Reservoirs to Drug Delivery to Viral
      Eradication.
AB  - Macrophages serve as host cells, inflammatory disease drivers and drug runners
      for human immunodeficiency virus infection and treatments. Low-level viral
      persistence continues in these cells in the absence of macrophage death. However,
      the cellular microenvironment changes as a consequence of viral infection with
      aberrant production of pro-inflammatory factors and promotion of oxidative
      stress. These herald viral spread from macrophages to neighboring CD4+ T cells
      and end organ damage. Virus replicates in tissue reservoir sites that include the
      nervous, pulmonary, cardiovascular, gut, and renal organs. However, each of these
      events are held in check by antiretroviral therapy. A hidden and often overlooked
      resource of the macrophage rests in its high cytoplasmic nuclear ratios that
      allow the cell to sense its environment and rid it of the cellular waste products
      and microbial pathogens it encounters. These phagocytic and intracellular killing
      sensing mechanisms can also be used in service as macrophages serve as cellular
      carriage depots for antiretroviral nanoparticles and are able to deliver
      medicines to infectious disease sites with improved therapeutic outcomes. These
      undiscovered cellular functions can lead to reductions in persistent infection
      and may potentially facilitate the eradication of residual virus to eliminate
      disease.

PMID- 29572682
TI  - The inhibitory effect of sodium baicalin on oseltamivir-resistant influenza A
      virus via reduction of neuraminidase activity.
AB  - Baicalin was identified as a neuraminidase (NA) inhibitor displaying anti
      influenza A virus (IAV) activity. However, its poor solubility in saline has
      limited its use in the clinic. We generated sodium baicalin and showed that it
      exhibited greatly increased solubility in saline. Its efficacy against
      oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) was evaluated in vitro
      and in vivo. Results showed that 10 MUM of sodium baicalin inhibited A/FM/1/47
      (H1N1), A/Beijing/32/92 (H3N2) and H1N1-H275Y in MDCK cells in a dose-dependent
      manner, with inhibitory rates of 83.9, 75.9 and 47.7%, respectively. Intravenous
      administration of sodium baicalin at 100 mg/kg/d enabled the survival of 20% of
      H1N1-H275Y-infected mice. The treatment alleviated body weight loss and lung
      injury. Moreover, sodium baicalin exerted a clear inhibitory effect on NAs. The
      IC50 values of sodium baicalin against H1N1-H275Y and cells-expressing
      A/Anhui/1/2013-R294K (H7N9-R294K) NA protein (N9-R294K) were 214.4 MUM and 216.3
      MUM. Direct interactions between sodium baicalin and NA were observed, and we
      simulated the interactions of sodium baicalin with N9-R294K and N9 near the
      active sites of OC-N9-R294K and OC-N9. The residues responsible for the sodium
      baicalin-N9-R294K and sodium baicalin-N9 interactions were the same, confirming
      that sodium baicalin exerts effects on wild-type and oseltamivir-resistant viral
      strains.

PMID- 29572683
TI  - Analysis of loxoprofen in tablets, patches, and equine urine as tert
      butyldimethylsilyl derivative by gas chromatography-mass spectrometry.
AB  - Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid
      type, which has used to treat musculoskeletal disorders in the horse racing
      industry. However, it has also used illicitly to mask clinical signs of
      inflammation and pain in racehorses. Thus, its accurate analysis has become an
      important issue in horse doping laboratories. In this study, an analytical method
      of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas
      chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15],
      [M-57], and [M-139] permitted the accurate and selective detection of loxoprofen.
      Under optimal conditions, this method showed good linearity (r >= 0.999) in the
      range of 10-500 ng/mL, repeatability (% relative standard deviation = 5.6-8.5),
      and accuracy (% relative error = - 0.3-0.9) with a detection limit of 1.0 ng.
      When applied to the analysis of loxoprofen in tablet and patch products,
      loxoprofen was positively identified as TBDMS derivative by GC-MS. The present
      method provided rapid and accurate determination of loxoprofen in patch and
      tablet products. Levels of loxoprofen were highest in equine urine at 0.5 and 1 h
      after oral administration with single dose (3 mg/kg) to three horses, and then
      rapidly reduced to below the lower limit of quantification at 24 h. Therefore,
      the present method will be useful for the pharmacokinetic study and doping tests
      for loxoprofen and other similar acidic drugs in horses.

PMID- 29572684
TI  - Preliminary assessment of groundwater hydrogeochemistry within Gilan, a northern
      province of Iran.
AB  - In four basins of Gilan province, groundwater samples were collected from 127
      piezometric wells to investigate the hydrogeochemistry of groundwater, and
      additionally its suitability for drinking and irrigation purposes. The average
      concentrations of major cations and anions follow the order of Ca2+ > Na+ > Mg2+
      > K+ and [Formula: see text], respectively. Using Piper diagram delineation,
      CaMgHCO3 was determined as the main hydrogeochemical facies of groundwater.
      According to Piper diagrams, Gibbs plots, and ionic ratios, silicate weathering
      and ion exchange are the major processes regulating the groundwater
      hydrochemistry. Furthermore, saturation indices (SIs) revealed that carbonate
      precipitation also plays an important role in aquifers. Among the processes,
      weathering of silicate minerals seems to be the dominant process. Comparing the
      analyzed major ions and physicochemical parameters with the WHO guideline values
      indicates that the potability of most groundwater samples is generally
      acceptable. Electrical conductivity (EC) and total dissolved solid (TDS)
      measurements along with sodium percentage (SP), sodium adsorption ratio (SAR),
      Kelley's index (KI), and residual sodium carbonate (RSC) calculations suggest
      that groundwater in many areas is suitable for irrigation use. Nonetheless, total
      hardness (TH) values ranging as high as 650.0 mg/l reveal many groundwater
      samples to be classified as hard and very hard, indicating a requirement for long
      term monitoring and further evaluation. The present study shows that the
      groundwater quality in Lahijan, Astaneh, and to a lesser extent Fouman drainage
      basins is lower than in Talesh. Therefore, intense monitoring programs towards
      enhanced water management practices are recommended before poorer quality
      groundwater is further utilized.

PMID- 29572685
TI  - [Statement and recommendation of the Professional Association of German
      Ophthalmologists (BVA), the German Ophthalmological Society (DOG) and the German
      Retina Society (RG) on central serous chorioretinopathy : Situation January
      2018].

PMID- 29572687
TI  - Biocompatibility and biomineralization assessment of mineral trioxide aggregate
      flow.
AB  - OBJECTIVE: Evaluate, in vivo, the biocompatibility via subcutaneous inflammatory
      tissue response and mineralization ability of the new MTA Flow compared to MTA
      Angelus and ProRoot MTA. MATERIALS AND METHODS: Forty male Wistar rats were
      assigned and received subcutaneous polyethylene tube implants containing the test
      materials and a control group with empty tube (n = 10 animals/group). After days
      7, 15, 30, and 60, the animals were euthanized and the polyethylene tubes were
      removed with the surrounding tissues. Inflammatory infiltrate and thickness of
      the fibrous capsule were histologically evaluated. Mineralization was analyzed by
      Von Kossa staining and under polarized light. Data were analyzed via Kruskal
      Wallis and Dunn's test with a significance level of 5%. RESULTS: MTA Angelus
      induced the mildest reaction after 7 (P > .05) and 15 days (P < .05) followed by
      MTA Flow, both cements achieving mild inflammatory reaction after 15 days.
      ProRoot MTA induced a severe inflammation on day 7 and was reducing after day 15
      (P > .05). No difference was observed after days 30 or 60 (P > .05). Von Kossa
      staining and birefringent structures were positive to all materials. CONCLUSIONS:
      At the end of the experiment, the novel MTA Flow showed biocompatibility and
      induced biomineralization in all time periods. CLINICAL RELEVANCE: The final
      consistence obtained in MTA Flow may facilitate several procedures, indicating
      that the MTA Flow has a promising application in endodontics.

PMID- 29572686
TI  - Anatomical locations in the oral cavity where surgical resections of oral
      squamous cell carcinomas are associated with a close or positive margin-a
      retrospective study.
AB  - OBJECTIVES: This study aimed to identify anatomical areas where resections of
      oral squamous cell carcinomas (OSCC) are significantly associated with close or
      positive margins. MATERIALS AND METHODS: This retrospective study included 330
      patients with a primary OSCC from 2010 to 2015. Patient and tumour data were
      categorised into three groups by R-status (R0 [clear], >= 5 mm, 185 patients
      [56.06%]; R1 [positive], < 1 mm, 24 patients [7.27%]; and R0 [close], 1-5 mm, 121
      patients [36.67%]). RESULTS: Areas where resections were significantly associated
      with close or positive margins were the hard palate (p < 0.001), buccal mucosa (p
      = 0.03), floor of the mouth (p = 0.004), lower alveolar ridge (p = 0.01),
      retromolar triangle (p = 0.005), and dorsal tongue (p = 0.02). CONCLUSIONS:
      Anatomical areas were identified in the oral cavity where it is challenging to
      resect OSCCs with an adequate safety margin. CLINICAL RELEVANCE: These results
      may enable surgeons to achieve a postulated safe distance during tumour
      resection, leading to a survival benefit for patients.

PMID- 29572688
TI  - Periodontal and endodontic infectious/inflammatory profile in primary periodontal
      lesions with secondary endodontic involvement after a calcium hydroxide-based
      intracanal medication.
AB  - OBJECTIVE: The aim of the present study was to investigate the effects of a
      calcium hydroxide-based intracanal medication (ICM) on periodontal and endodontic
      infectious/inflammatory contents and on periodontal clinical parameters in teeth
      with primary periodontal lesion and secondary endodontic involvement. MATERIALS
      AND METHODS: Ten patients with abnormal pulp test results and deep probing depth
      derived from primary periodontal disease with secondary endodontic involvement
      were included. Samples were collected from root canals (RC) and periodontal
      pockets (PP) in order to investigate the microbiological status, levels of
      endotoxin (LPS), cytokines, and matrix metalloproteinases (MMP), before and after
      ICM. PCR was used for microbiological assessment. The kinetic-chromogenic LAL
      assay was used for LPS quantification. Quantikine ELISA kits were used for
      measurement of IL-1 alpha, IL-1 beta, TNF-alpha, PGE2, MMP-2, MMP-3, MMP-8, MMP
      9, and MMP-13 levels. The statistical analyses were made using the Friedman and
      Wilcoxon tests (p < 0.05). T test was used to compare data on periodontal
      characteristics. RESULTS: ICM did not reduce the number of microorganisms in PP
      and RC, except for Fusobacterium nucleatum in RC. There was a significant
      reduction in LPS, MMPs, IL-1 beta, and TNF-alpha levels in PP after ICM. In RC,
      LPS, MMP13, PGE2, and IL-1beta levels remained unaltered (p > 0.05); however, the
      levels of the other MMPs and cytokines were reduced (p < 0.05). After 1 year of
      the root canal treatment, tooth mobility was significantly reduced (p <= 0.05).
      CONCLUSIONS: The use of a calcium hydroxide-based ICM showed positive effects for
      periodontal treatment prognosis, as it reduced LPS, cytokine, and MMP levels in
      periodontal pockets. CLINICAL SIGNIFICANCE: Patients presenting deep probing
      depth and undergoing periodontal treatment for at least 6 months, with no
      positive response to periodontal therapy, might benefit with the endodontic
      treatment.

PMID- 29572689
TI  - Assessing the effects of different agro-residue as substrates on growth cycle and
      yield of Grifola frondosa and statistical optimization of substrate components
      using simplex-lattice design.
AB  - Grifola frondosa is an economically important edible and medicinal mushroom
      usually produced on substrate consisting of sawdust supplemented with wheat bran.
      Cultivation of G. frondosa on crop straw (corn cob, corn straw, rice straw, and
      soybean straw) as a substrate was optimized by using the D-optimum method of the
      simplex-lattice design, and the alternative of crop straw as a substitute for
      sawdust in the substrate composition was determined by the optimized model. The
      results showed that there was a significant positive correlation existing between
      the yield and corn cob. The growth cycle was negatively correlated with sawdust,
      corn cob and soybean straw, with sawdust significantly shortening the growth
      cycle of G. frondosa. The optimized high-yielding formula included 73.125% corn
      cob, 1.875% rice straw, 23% wheat bran and 2% light calcium carbonate (CaCO3)
      (C/N = 48.40). The average yield of the first flush was 134.72 +/- 4.24 g/bag,
      which was increased by 39.97% compared with the control formula. The biological
      efficiency (BE) was 44.91 +/- 1.41%, which was increased by 38.53% compared with
      the control. Based on the results of this study, corn cob can replace sawdust as
      one of the main cultivation substrates of G. frondosa.

PMID- 29572690
TI  - Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta
      Analysis.
AB  - Low translational yield for stroke may reflect the focus of discovery science on
      rodents rather than humans. Just how little is known about human neuronal
      ischaemic responses is confirmed by systematic review and meta-analysis revealing
      that data for the most commonly used SH-SY5Y human cells comprises only 84
      papers. Oxygen-glucose deprivation, H2O2, hypoxia, glucose-deprivation and
      glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury,
      respectively, with a dose-response relationship found only for H2O2 injury (R2 =
      29.29%, p < 0.002). Heterogeneity (I2 = 99.36%, df = 132, p < 0.0001) was largely
      attributable to the methods used to detect injury (R2 = 44.77%, p < 0.000) with
      cell death assays detecting greater injury than survival assays (- 71 vs - 47%,
      R2 = 28.64%, p < 0.000). Seventy-four percent of publications provided no
      description of differentiation status, but in the 26% that did, undifferentiated
      cells were susceptible to greater injury (R2 = 4.13%, p < 0.047). One hundred and
      sixty-nine interventions improved average survival by 34.67% (p < 0.0001). Eighty
      eight comparisons using oxygen-glucose deprivation found both benefit and harm,
      but studies using glutamate and H2O2 injury reported only improvement. In studies
      using glucose deprivation, intervention generally worsened outcome. There was
      insufficient data to rank individual interventions, but of the studies reporting
      greatest improvement (> 90% effect size), 7/13 were of herbal medicine
      constituents (24.85% of the intervention dataset). We conclude that surprisingly
      little is known of the human neuronal response to ischaemic injury, and that the
      large impact of methodology on outcome indicates that further model validation is
      required. Lack of evidence for randomisation, blinding or power analysis suggests
      that the intervention data is at substantial risk of bias.

PMID- 29572692
TI  - An extension of the Marcus equation: the Marcus potential energy function.
AB  - An analytic potential function consistent with the Marcus equation for activation
      energy is formulated and used to reveal new insights into the activation process
      in chemical reactions. As for the Marcus equation, the new potential function
      depends only on two parameters, the reaction energy and the activation energy (or
      the so-called Marcus intrinsic activation energy). Combination of the Marcus
      potential with the reaction force analysis provides two-parameter analytic
      expressions for the reaction force, reaction force constant, and reaction works.
      Moreover, since the parameters necessary to define the Marcus potential energy
      function can be obtained experimentally, the present model may produce
      experimental analytic potentials allowing for new and interesting applications,
      thus emerging as a powerful tool to characterize activation processes in chemical
      reactions.

PMID- 29572691
TI  - Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship
      Intervention.
AB  - PURPOSE OF REVIEW: Fluoroquinolones are a commonly prescribed antibiotic class
      that has come under scrutiny in recent years due to mounting evidence of
      association between adverse drug events, C. difficile infection and isolation of
      antibiotic-resistant bacteria. RECENT FINDINGS: Inpatient antimicrobial
      stewardship (AMS) programs have a toolbox of potential interventions to curb
      inappropriate antibiotic use, prevent antibiotic-associated adverse drug events,
      and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the
      acute care setting have demonstrated beneficial effects, including decreased
      rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a
      simple blanket restriction policy may "squeeze the antibiotic balloon" and will
      likely be insufficient if not implemented in conjunction with other AMS
      interventions. There is a growing body of evidence to support formulary
      restriction of fluoroquinolones in the acute care setting to decrease rates of C.
      difficile infection and development of ESBL-producing organisms. Data on how to
      best implement these restrictions or how to implement outside of acute care
      settings is limited.

PMID- 29572693
TI  - Human chorionic gonadotropin serum levels following ovulation triggering and IVF
      cycle outcome.
AB  - PURPOSE: The clinical significance of serum hCG levels after ovulation triggering
      was studied previously with conflicting results. Our aim was to study the
      correlation of hCG levels on the day after ovulation triggering using recombinant
      hCG (r-hCG) with treatment outcome. METHODS: A prospective observational study of
      all fresh IVF/ICSI cycles in a single medical center, between January 2015 and
      June 2016, was performed. hCG serum levels were obtained 10-12 h following
      ovulation triggering with 250 mcg r-hCG. Clinical and laboratory outcome
      parameters were compared between cycles with serum hCG above and below median
      level. A multivariate regression analysis was performed in order to study the
      association between hCG levels and live birth rate, after controlling for
      confounders. RESULTS: Overall, 326 cycles were included. Median serum hCG level
      was 91.35 IU/L. hCG levels were lower as age and BMI were higher (p = 0.004, p <
      0.001, respectively). The study groups did not differ with regard to clinical
      pregnancy rate (p = 0.14), live birth rate (p = 0.09), fertilization rate (p =
      0.45), or metaphase II oocyte rate (p = 0.68). On multivariate regression
      analysis, hCG level was not associated with live birth (aOR 0.99, 95% CI 0.98
      1.005), after controlling for patient's age and BMI. CONCLUSIONS: hCG levels on
      the day after ovulation triggering with 250 mcg r-hCG are inversely correlated
      with patient age and BMI. However, they are not correlated with any clinical or
      laboratory outcome parameter. Therefore, testing for hCG levels after ovulation
      induction seems futile and cannot be recommended.

PMID- 29572694
TI  - Total urokinase-type plasminogen activator (uPA) levels in seminal plasma are
      associated with positive assisted reproductive technology outcomes.
AB  - PURPOSE: The plasminogen/plasmin system is an important extracellular protease
      system whose function has been implicated in male reproductive function. However,
      its clinical relevance to fertility in human assisted reproduction technologies
      has not been systematically investigated. Here, we examined whether total and
      active populations of urokinase-type plasminogen activator (uPA) in human seminal
      plasma and spermatozoa are predictive of pregnancy outcome in couples undergoing
      insemination or intracytoplasmic sperm injection (ICSI). METHODS: Seminal samples
      from 182 men, 5 donors, 21 patients attending the clinic for infertility
      screening, and 156 for assisted reproduction technology (ART) treatment
      (insemination and ICSI), were evaluated. Total uPA in seminal plasma and
      spermatozoa as well as active uPA in seminal plasma were measured by ELISA. Sperm
      quality parameters and fertility outcomes following insemination or ICSI were
      correlated with the uPA values. RESULTS: Active uPA in seminal plasma was
      positively correlated to the volume of the ejaculate, total number of spermatozoa
      in the ejaculate, and total motility. However, these values were not prognostic
      of fertility outcomes. Total uPA in spermatozoa was inversely related to sperm
      concentration, total sperm in ejaculate, morphology, and total and progressive
      motility, and this measure was not related to fertility. Importantly, however,
      higher values of total uPA in seminal plasma were detected in cases that resulted
      in pregnancy compared to those that did not follow insemination and ICSI
      treatment. CONCLUSIONS: Taken together, these findings lay the foundation for
      further understanding the mechanism by which total uPA in seminal plasma affects
      fertility and how this marker can be used as a predictor of ART outcomes.

PMID- 29572695
TI  - The effect of swim-up and gradient sperm preparation techniques on
      deoxyribonucleic acid (DNA) fragmentation in subfertile patients.
AB  - PURPOSE: To compare the effect of two different sperm preparation techniques,
      including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA)
      fragmentation status of semen samples from unexplained and mild male factor
      subfertile patients undergoing intrauterine insemination (IUI). DESIGN: A
      prospective randomized study was conducted in 65 subfertile patients, including
      34 unexplained and 31 male factor infertility to compare basal and post-procedure
      DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA
      fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in
      two portions of each sample of semen that was prepared with either swim-up or
      gradient techniques. Sperm motility and morphology were also assessed based on
      WHO 2010 criteria. RESULTS: Swim-up but not gradient method yielded a
      statistically significant reduction in the DNA fragmented sperm rate after
      preparation as compared to basal rates, in the semen samples of both unexplained
      (41.85 +/- 22.04 vs. 28.58 +/- 21.93, p < 0.001 for swim-up; and 41.85 +/- 22.04
      vs. 38.79 +/- 22.30, p = 0.160 for gradient) and mild male factor (46.61 +/-
      19.38 vs. 30.32 +/- 18.20, p < 0.001 for swim-up and 46.61 +/- 19.38 vs. 44.03 +/
      20.87, p = 0.470 for gradient) subgroups. CONCLUSIONS: Swim-up method
      significantly reduces sperm DNA fragmentation rates and may have some prognostic
      value on intrauterine insemination in patients with decreased sperm DNA
      integrity.

PMID- 29572697
TI  - Movement Patterns of Small Rodents in Lassa Fever-Endemic Villages in Guinea.
AB  - The Natal multimammate mouse (Mastomys natalensis) is the reservoir host of Lassa
      arenavirus, the etiological agent of Lassa fever in humans. Because there exists
      no vaccine for human use, rodent control and adjusting human behavior are
      currently considered to be the only options for Lassa fever control. In order to
      develop efficient rodent control programs, more information about the host's
      ecology is needed. In this study, we investigated the spatial behavior of M.
      natalensis and other small rodents in two capture-mark-recapture and four dyed
      bait (Rhodamine B) experiments in Lassa fever-endemic villages in Upper Guinea.
      During the capture-mark-recapture studies, 23% of the recaptured M. natalensis
      moved between the houses and proximate fields. While M. natalensis was found over
      the entire study grid (2 ha), other rodent species (Praomys daltoni, Praomys
      rostratus, Lemniscomys striatus, Mus spp.) were mostly trapped in the surrounding
      fields. Distances between recapture occasions never exceeded 100 m for all rodent
      species. During the dyed bait experiments, 11% of M. natalensis and 41% of P.
      daltoni moved from the fields to houses. We conclude that commensal M. natalensis
      easily moves between houses and proximate fields in Guinea. We therefore consider
      occasional domestic rodent elimination to be an unsustainable approach to reduce
      Lassa virus transmission risk to humans, as M. natalensis is likely to reinvade
      houses quickly from fields in which rodents are not controlled. A combination of
      permanent rodent elimination with other control strategies (e.g., make houses
      rodent proof or attract predators) could be more effective for Lassa fever
      control, but must be further investigated.

PMID- 29572696
TI  - Endoscopic Management of Difficult Bile Duct Stones.
AB  - PURPOSE OF REVIEW: In 10-15% of the cases, conventional methods for removing bile
      duct stones by ERCP/balloon-basket extraction fail. The purpose of this review is
      to describe endoscopic techniques in managing these "difficult bile duct stones."
      RECENT FINDINGS: Endoscopic papillary large balloon dilation with balloon
      extraction +/- mechanical lithotripsy is the initial approach used to retrieve
      large bile duct stones. With advent of digital cholangioscopy, electrohydraulic
      and laser lithotripsy are gaining popularity. Enteroscopy-assisted or
      laparoscopic-assisted approaches can be used for those with gastric bypass
      anatomy. Difficulties in removing bile duct stones can be related to stone
      related factors such as the size and location of the stone or to altered anatomy
      such as stricture in the bile duct or Roux-en-Y anatomy. Several endoscopy
      approaches and techniques have described in the recent past that have greatly
      enhanced our ability to remove these "difficult" bile duct stones.

PMID- 29572698
TI  - 2018 Letter from the Editor-in-Chief.

PMID- 29572699
TI  - Differential diagnosis of Ixodes ricinus and Ixodes persulcatus: nymphs and
      larvae.
AB  - We developed a method for differential diagnosis of nymphs and larvae of sheep
      (Ixodes ricinus (L.)) and taiga (I. persulcatus Sch.) ticks (Parasitiformes:
      Ixodidae) which allows to identify live material in the field.

PMID- 29572700
TI  - Impact of the erineum strain of Colomerus vitis (Acari: Eriophyidae) on the
      development of plants of grapevine cultivars of Iran.
AB  - The present experiment was aimed at determining the influence of the grape
      erineum strain of Colomerus vitis (GEM) (Acari: Eriophyidae) on responses of
      local grapevine cultivars. GEM was applied at five density levels to each of five
      cultivars, i.e. Shahani, Sahebi Uroomie, Khalili Bovanat, Rishbaba and Sezdang
      Ghalat (listed from early to late grape ripening). The experiment was performed
      in a full factorial design (12 replicates each) and effects of the mite on the
      relative content of leaf chlorophyll, internode and cane length, leaf area and
      weight, number and size of the erinea, and percentage of leaves with erinea were
      investigated. Also mite density on leaves and in buds was assessed. Data were
      analyzed with a two-way ANOVA followed by Tukey's test to separate means among
      treatment levels and cultivars. The relative content of chlorophyll (expressed in
      Spad units) in infested leaves was reduced along with an increase in mite density
      and it was shown to be highly significant at the two higher mite density levels
      for Khalili Bovanat, Rishbaba and Sezdang Ghalat; Shahani and Sahebi Uroomie
      leaves appeared to be less affected by mite infestation. The highest mite density
      treatment displayed a strong correlation with weight (positive correlation) and
      size (negative correlation) of the leaves of four cultivars; leaves of Sahebi
      Uroomie appeared to be less affected. The reduced internode length was weak in
      infested plants. Most infested plants produced shorter canes and their lengths
      appeared to have a strong negative correlation with the highest mite density in
      four cultivars; canes of Sahebi Uroomie did not appear affected. At the highest
      mite density, canes of Khalili Bovanat and Sahebi Uroomie displayed the most and
      the least shortening effects, respectively. The percentage of leaves with erinea,
      as well as the number of erinea per leaves and the diameter of erinea increased
      along with the mite population density. The mite densities in buds (April 2014)
      and on leaves with erinea (in November 2013) were higher at the highest treatment
      level in the medium-late (Rishbaba) and late ripening (Sezdang Ghalat) cultivars,
      than in the early and early-medium ripening ones. Almost all data collected in
      the current experiment allowed the conclusion that Sahebi Uroomie and Shahani
      were less affected than the other cultivars (Khalili Bovanat, Rishbaba and
      Sezdang Ghalat).

PMID- 29572701
TI  - Diacylglycerol kinase alpha inactivation is an integral component of the
      costimulatory pathway that amplifies TCR signals.
AB  - The arsenal of cancer therapies has evolved to target T lymphocytes and restore
      their capacity to destroy tumor cells. T cells rely on diacylglycerol (DAG) to
      carry out their functions. DAG availability and signaling are regulated by the
      enzymes diacylglycerol kinase (DGK) alpha and zeta, whose excess function drives
      T cells into hyporesponsive states. Targeting DGKalpha is a promising strategy
      for coping with cancer; its blockade could reinstate T-cell attack on tumors
      while limiting tumor growth, due to positive DGKalpha functions in several
      oncogenic pathways. Here, we made a side-by-side comparison of the effects of
      commercial pharmacological DGK inhibitors on T-cell responses with those promoted
      by DGKalpha and DGKzeta genetic deletion or silencing. We show the specificity
      for DGKalpha of DGK inhibitors I and II and the structurally similar compound
      ritanserin. Inhibitor treatment promoted Ras/ERK (extracellular signal-regulated
      kinase) signaling and AP-1 (Activator protein-1) transcription, facilitated
      DGKalpha membrane localization, reduced the requirement for costimulation, and
      cooperated with enhanced activation following DGKzeta silencing/deletion. DGKiII
      and ritanserin had similar effects on TCR proximal signaling, but ritanserin
      counteracted long-term T-cell activation, an effect that was potentiated in
      DGKalpha-/- cells. In contrast with enhanced activation triggered by
      pharmacological inhibition, DGKalpha silencing/genetic deletion led to impaired
      Lck (lymphocyte-specific protein tyrosine kinase) activation and limited
      costimulation responses. Our results demonstrate that pharmacological inhibition
      of DGKalpha downstream of the TCR provides a gain-of-function effect that
      amplifies the DAG-dependent signaling cascade, an ability that could be exploited
      therapeutically to reinvigorate T cells to attack tumors.

PMID- 29572703
TI  - Using a Small Cash Incentive to Increase Survey Response.
AB  - Surveys tend to yield low response rates among human service professionals. This
      study examined whether a randomly-assigned prepaid $2 incentive increased
      response rates over time, and was cost-effective for increasing response count,
      among social workers and volunteer mediators. The incentive was enclosed with a
      mixed-mode survey of factors related to burnout and intention-to-remain. The
      incentive increased response rates over time. The effect of the incentive did not
      differ between mediators and social workers. The $2 incentive was not cost
      effective for increasing response count. Implications are discussed for reducing
      nonresponse bias, decreasing time-to-response, and considering response rate
      versus response count.

PMID- 29572702
TI  - Depleted polymorphonuclear leukocytes in human metastatic liver reflect an
      altered immune microenvironment associated with recurrent metastasis.
AB  - BACKGROUND: Hepatic immunity, normally protective against neoplasia, is subverted
      in colorectal liver metastasis (CRLM). Here, we compare the inflammatory
      microenvironment of CRLM-bearing liver tissue to donor liver. METHODS: Twenty
      five patients undergoing resection for CRLM were recruited, 13 of whom developed
      intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and
      normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies
      were obtained during transplantation. Biopsies were cultured and conditioned
      media (CM) screened for 102 inflammatory mediators. Twelve of these were
      validated by Luminex assay. Transwell assays measured cancer cell chemotaxis.
      Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E
      sections. RESULTS: Fewer periportal tissue-resident PMN were present in
      metastatic liver compared to donor liver. Patients with the fewest PMN in liver
      tissue distal to their tumour had a shorter time to intrahepatic recurrence (P <
      0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in
      liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated
      equally towards CM of all regions of metastatic liver but not towards donor liver
      CM. CONCLUSIONS: The local inflammatory environment may affect both immune cell
      infiltration and cancer cell migration contributing to recurrence following
      resection for CRLM.

PMID- 29572704
TI  - Prognostic Impact of R0 Resection and Targeted Therapy for Colorectal Cancer with
      Synchronous Peritoneal Metastasis.
AB  - BACKGROUND: The National Comprehensive Cancer Network guidelines recommend R0
      resection and targeted therapy, a combination of cytotoxic and molecular targeted
      agents, such as bevacizumab, cetuximab, and panitumumab, for colorectal cancer
      with synchronous peritoneal metastasis (M1c). While these therapeutic strategies
      are drawing attention, their efficacy has not been fully examined. METHODS: The
      study population comprised 248 consecutive M1c patients who were treated at the
      National Cancer Center Hospital from 1997 to 2013. Multivariate analyses were
      performed to evaluate relationships between overall survival and R0 resection and
      targeted therapy using Cox proportional hazards regression models. RESULTS: The 3
      year overall survival (3 yOS) was 19.5%, and median survival time (MST) was 16.2
      months in 248 M1c patients. R0 resection was performed in 34 patients (14%),
      yielding a 3-year overall survival (OS) of 48.3% and median survival time (MST)
      of 29.9 months. Targeted therapy was performed in 54 patients (22%) at least once
      during the course of treatment, yielding a 3-yr OS of 38.2% and MST of 23.9
      months. After adjusting for other key clinical factors, such as the number of
      organs involved with metastases, performance status, primary tumor site, and
      extent of peritoneal metastasis, both R0 resection and targeted therapy were
      independent factors associated with longer OS. Targeted therapy was associated
      with a significantly longer OS compared with multiple cytotoxic agent therapy
      [hazard ratio 0.65; 95% confidence interval (0.44-0.94); p = 0.02]. CONCLUSIONS:
      If achievable, R0 resection is a desirable therapeutic strategy for patients with
      M1c colorectal cancer. Moreover, targeted therapy might be the optimal
      chemotherapy in this patient population.

PMID- 29572705
TI  - Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an
      Indication for Axillary Dissection?
AB  - BACKGROUND/OBJECTIVE: Intraoperative evaluation of sentinel lymph nodes (SLNs)
      after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the
      primary surgical setting, particularly for small tumor deposits. Additional tumor
      burden seen with isolated tumor cells (ITCs) and micrometastases following
      primary surgery is low; however, it is unknown whether the same is true after
      NAC. We examined the false-negative rate of intraoperative frozen section (FS)
      after NAC, and the association between SLN metastasis size and residual disease
      at axillary lymph node dissection (ALND). METHODS: Patients undergoing SLN biopsy
      after NAC were identified. The association between SLN metastasis size and
      residual axillary disease was examined. RESULTS: From July 2008 to July 2017, 702
      patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530
      were negative; 33 negative cases were positive on final pathology (false-negative
      rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further
      disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases.
      Fifty-nine percent of patients with micrometastases and 63% with macrometastases
      had one or more additional positive nodes at ALND. Among those with a false
      negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had
      macrometastases; 17 had ALND and 59% had one or more additional positive lymph
      nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with
      micrometastases had additional nodal metastases at ALND. CONCLUSION: Low-volume
      SLN disease after NAC is not an indicator of a low risk of additional positive
      axillary nodes and remains an indication for ALND, even when not detected on
      intraoperative FS.

PMID- 29572706
TI  - A National-Level Validation of the New American Joint Committee on Cancer 8th
      Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.
AB  - INTRODUCTION: The 8th edition of the American Joint Committee on Cancer (AJCC)
      updated the staging system of anal squamous cell cancer (ASCC) by subdividing
      stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG
      98-11 trial. We aimed to validate this new subclassification utilizing two
      nationally representative databases. MATERIALS: The National Cancer Database
      (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER)
      database [1988-2013] were queried to identify patients with stage II ASCC.
      RESULTS: A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB
      (> 5 cm) patients were identified in the NCDB and SEER databases, respectively.
      Compared with stage IIB patients, stage IIA patients within the NCDB were more
      often females with fewer comorbidities. No significant differences were observed
      between age, race, receipt of chemotherapy and radiation, and mean radiation
      dose. Demographic, clinical, and pathologic characteristics were comparable
      between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA
      versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p
      < 0.001). After adjustment for available demographic and clinical confounders,
      stage IIB was significantly associated with worse survival in both cohorts
      (hazard ratio 1.58 and 2.01, both p < 0.001). CONCLUSION: This study validates
      the new AJCC subclassification of stage II anal cancer into A and B based on size
      (2-5 cm vs. > 5 cm) in the general ASCC population. AJCC stage IIB patients
      represent a higher risk category that should be targeted with more
      aggressive/novel therapies.

PMID- 29572707
TI  - Prescription Drug Use and Cost Trends Among Medicaid-Enrolled Children with
      Disruptive Behavioral Disorders.
AB  - Disruptive behavior disorders (DBDs) are the most common mental health conditions
      in children. These conditions profoundly affect healthcare utilization and costs.
      Service use, costs, and diagnostic trends among pediatric Medicaid beneficiaries
      provide information regarding healthcare quality and potential for smarter
      spending. Using nationwide Medicaid administrative data, this study investigates
      diagnoses, prescription drug fills, and payments in 49 states and D.C. from 2006
      to 2009 in Medicaid beneficiaries age 20 and under. Psychotherapeutic drug
      prescriptions and payments were calculated as a proportion of prescription
      totals. Results were considered by age, gender, race, and state. The results show
      a trend of increasing DBD diagnosis. Among prescription claims for children with
      diagnosed DBD, psychotherapeutic drug claims represented 30-40% of prescription
      claims but over half of prescription costs. This study indicates increasing
      clinical and financial needs for Medicaid-enrolled children with DBDs. Medicaid
      could potentially foster reforms in pediatric DBD treatments, particularly
      regarding medication use.

PMID- 29572709
TI  - The antiproliferative effect of pasireotide LAR alone and in combination with
      everolimus in patients with medullary thyroid cancer: a single-center, open
      label, phase II, proof-of-concept study.
AB  - PURPOSE: Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid
      C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and
      everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine
      tumours. Aim of this study was to evaluate pasireotide alone and in combination
      with everolimus in patients with MTC. METHODS: Patients with progressive
      metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for
      at least 6 months. Patients exhibiting progressive disease received everolimus 10
      mg/d as combination therapy. Primary endpoint was progression free survival
      (PFS). Secondary endpoints included, overall survival, objective response rates,
      change in circulating markers, safety. Study registration no. NCT01625520.
      RESULTS: Nineteen consecutive patients were enrolled. Median follow-up was 31
      months. Median PFS with pasireotide was 36 months (95% CI: 19.5-52.5). Nine
      patients (47%) had tumour progression: seven of them started everolimus in
      combination with pasireotide, achieving a median PFS of 9.0 months (95% CI: 0
      21.83). Five of them (71%) had further tumour progression, one objective response
      (14.3%), one stopped treatment because of pulmonary embolism. Pasireotide alone
      and with everolimus was safe and required withdrawal only in one case. Diarrhoea
      and hyperglycaemia were the most frequent adverse events with pasireotide (grade
      3 in 5.3% each). Hyperglycaemia was the most frequent grade 3 toxicity with the
      combination therapy (28.6%). CONCLUSIONS: Pasireotide therapy shows
      antiproliferative effects in persistent postoperative MTC suggesting further
      investigation on larger series of patients. In progressive MTC lesions, the
      combination pasireotide plus everolimus may be of benefit. Both schemes were safe
      and well tolerated.

PMID- 29572708
TI  - Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes:
      review of literature and clinical perspectives.
AB  - PURPOSE: Klinefelter syndrome (KS), the most frequent chromosomic abnormality in
      males, is associated with hypergonadotropic hypogonadism and an increased risk of
      cardiovascular diseases (CVD). The mechanisms involved in increasing risk of
      cardiovascular morbidity and mortality are not completely understood. This review
      summarises the current understandings of the complex relationship between KS,
      metabolic syndrome and cardiovascular risk in order to plan future studies and
      improve current strategies to reduce mortality in this high-risk population.
      METHODS: We searched PubMed, Web of Science, and Scopus for manuscripts published
      prior to November 2017 using key words "Klinefelter syndrome" AND "insulin
      resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular
      disease" OR "testosterone". Manuscripts were collated, studied and carried
      forward for discussion where appropriate. RESULTS: Insulin resistance, metabolic
      syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the
      general population; however, the contribution of hypogonadism to metabolic
      derangement is highly controversial. Whether this dangerous combination of risk
      factors fully explains the CVD burden of KS patients remains unclear. In
      addition, testosterone replacement therapy only exerts a marginal action on the
      CVD system. CONCLUSION: Since fat accumulation and distribution seem to play a
      relevant role in triggering metabolic abnormalities, an early diagnosis and a
      tailored intervention strategy with drugs aimed at targeting excessive visceral
      fat deposition appear necessary in patients with KS.

PMID- 29572710
TI  - Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine
      replacement or suppressive therapy: a meta-analysis.
AB  - PURPOSE: To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L
      T4 in patients on L-T4 replacement or suppressive therapy. METHODS: The Cochrane
      Library, PubMed, Embase, and Web of Science databases were searched to identify
      relevant articles. All prospective or randomized controlled studies (RCTs)
      comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or
      suppressive therapy were included in the analysis. RESULTS: Overall, the initial
      search of the four databases identified 1278 published studies; of these, eight
      studies were ultimately included in the meta-analysis. TSH (thyroid stimulating
      hormone) levels were significantly suppressed in patients on liquid L-T4 compared
      with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4
      malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59,
      -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a
      statistically significant difference in patients on L-T4 suppressive therapy
      without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were
      significantly normalized in patients on liquid L-T4 compared with those on tablet
      L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = 
      3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did
      not show a statistically significant difference in patients on L-T4 replacement
      therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06).
      CONCLUSION: Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4
      replacement or suppressive therapy with malabsorption. No significant differences
      were observed in patients without malabsorption. Further studies should be
      conducted to verify these findings.

PMID- 29572713
TI  - Tree-in-bud sign.

PMID- 29572711
TI  - Low-dose Synachten test with measurement of salivary cortisol in adult patients
      with beta-thalassemia major.
AB  - PURPOSE: Beta-thalassemia major is a severe, congenital hematological disorder
      and, if untreated, leads to early mortality. Progress in therapeutical strategies
      improved clinical outcomes and life expectancy; however, increased survival led
      to the development of new disorders, including endocrinopathies. Little is known
      on the possible impairment of adrenocortical function, a potentially life
      threatening condition, in long-term thalassaemic survivors. We therefore decided
      to assess adrenal reserve and the value of salivary cortisol during ACTH
      stimulation in the diagnosis of adrenocortical insufficiency in adult patients
      with beta-thalassemia major. METHODS: Cross-sectional study including 72 adults
      with beta-thalassemia major. Patients were tested with 1 ug ACTH for serum and
      salivary cortisol. RESULTS: Subnormal serum cortisol responses to ACTH
      stimulation (i.e., <500 nmol/l) were registered in 15 out of 72 patients.
      Salivary cortisol increased in parallel with serum cortisol and a clear-cut
      positive correlation was detected at each timepoint. Moreover, peak salivary
      cortisol values after ACTH stimulation were significantly lower in patients with
      impaired adrenal reserve (513.6 +/- 52.33 vs. 914.1 +/- 44.04 nmol/l p < 0.0001).
      CONCLUSIONS: Our results attest to the need for testing for adrenal insufficiency
      among adult thalassaemic patients, as up to 20% presented impaired adrenal
      reserve. Salivary and serum cortisol levels during stimulation with ACTH were
      closely correlated and the use of salivary cortisol sampling during ACTH testing
      may represent a surrogate to serum cortisol in these patients.

PMID- 29572712
TI  - [Imaging of gastrointestinal inflammation : Characteristic patterns and signs].
AB  - CLINICAL PROBLEM: Pathological conditions of the gastrointestinal tract can
      result from various disorders, including inflammatory, infectious, neoplastic,
      and ischemic diseases. RADIOLOGICAL STANDARD PROCEDURES: Cross-sectional imaging
      techniques have largely replaced many of the conventional fluoroscopic
      examinations, such as small bowel follow-through and double-contrast barium
      enema. The former allow for time-efficient, accurate, and minimally invasive
      diagnostics. Therefore, they have become important diagnostic tools for the
      evaluation of inflammatory diseases of the gastrointestinal tract. The distension
      of the intestinal lumen with orally administered neutral contrast media improves
      not only the evaluation of the intraluminal aspect, but also of the cross
      sectional appearance. Furthermore, with cross-sectional imaging techniques, the
      additional assessment of the extraintestinal structures and organs is also
      possible. METHODICAL INNOVATIONS AND ASSESSMENT: With the ongoing development of
      scanner and software technology, pathologic conditions of the gastrointestinal
      wall can be characterized in more detail by both computed tomography and magnetic
      resonance imaging. A structured approach, based on the analysis of typical
      radiological signs and patterns, combined with the evaluation of extraintestinal
      findings may help to assign the observed imaging findings to specific disease
      groups. RECOMMENDATIONS: This article summarizes common signs and typical
      patterns frequently seen in inflammatory conditions of the gastrointestinal
      tract. A systematic approach for structured analysis of specific and nonspecific
      imaging features and common pitfalls may aid in the interpretation and help to
      narrow the spectrum of potential differential diagnoses.

PMID- 29572714
TI  - Accuracy of liver surface nodularity quantification on MDCT for staging hepatic
      fibrosis in patients with hepatitis C virus.
AB  - PURPOSE: To evaluate semi-automated measurement of liver surface nodularity (LSN)
      on MDCT in a cause-specific cohort of patients with chronic hepatitis C virus
      infection (HCV) for identification of hepatic fibrosis (stages F0-4). METHODS:
      MDCT scans in patients with known HCV were evaluated with an independently
      validated, semi-automated LSN measurement tool. Consecutive LSN measurements
      along the anterior liver surface were performed to derive mean LSN scores. Scores
      were compared with METAVIR fibrosis stage (F0-4). Fibrosis stages F0-3 were based
      on biopsy results within 1 year of CT. Most patients with cirrhosis (F4) also had
      biopsy within 1 year; the remaining cases had unequivocal clinical/imaging
      evidence of cirrhosis and biopsy was not indicated. RESULTS: 288 patients
      (79F/209M; mean age, 49.7 years) with known HCV were stratified based on METAVIR
      fibrosis stage: F0 (n = 43), F1 (n = 29), F2 (n = 53), F3 (n = 37), and F4 (n =
      126). LSN scores increased with increasing fibrosis (mean: F0 = 2.3 +/- 0.2, F1 =
      2.4 +/- 0.3, F2 = 2.6 +/- 0.5, F3 = 2.9 +/- 0.6, F4 = 3.8 +/- 1.0; p < 0.001).
      For identification of significant fibrosis (>= F2), advanced fibrosis (>= F3),
      and cirrhosis (>= F4), the ROC AUCs were 0.88, 0.89, and 0.90, respectively. The
      sensitivity and specificity for significant fibrosis (>= F2) using LSN threshold
      of 2.80 were 0.68 and 0.97; for advanced fibrosis (>= F3; threshold = 2.77) were
      0.83 and 0.85; and for cirrhosis (>= F4, LSN threshold = 2.9) were 0.90 and 0.80.
      CONCLUSION: Liver surface nodularity assessment at MDCT allows for accurate
      discrimination of intermediate stages of hepatic fibrosis in a cause-specific
      cohort of patients with HCV, particularly at more advanced levels.

PMID- 29572715
TI  - Right ventricular lead location, right-left ventricular lead interaction, and
      long-term outcomes in cardiac resynchronization therapy patients.
AB  - BACKGROUND: The effects of right ventricular (RV) lead location and the
      combination of RV and left ventricular (LV) lead locations on long-term outcomes
      in patients receiving cardiac resynchronization therapy with defibrillator (CRT
      D) are not well understood. METHODS: Our cohort consisted of 743 CRT-D patients
      from MADIT-CRT. We evaluated long-term death and combined heart failure or death
      (HF/death) in patients with non-apical RV vs. apical RV leads. We further
      assessed these long-term outcomes based on the combination of RV and LV leads,
      termed "RV-LV lead interaction." Patients with non-apical RV and apical LV leads
      and those with apical RV and non-apical LV leads were described to have
      "discordant RV and LV leads." Patients with RV and LV leads that were both non
      apical or both apical were defined to have "concordant RV and LV leads." RESULTS:
      There were no differences in death and HF/death between patients with non-apical
      RV vs. apical RV leads. However, patients with non-apical RV and apical LV leads
      had higher mortality risk, relative to those with apical RV and non-apical LV
      leads (HR = 4.06, 95% CI 1.73-9.53, p = 0.001) as well as those with both leads
      in the non-apical (HR = 3.82, 95% CI 1.33-10.98, p = 0.013) or apical (HR = 3.40,
      95% CI 1.24-9.37, p = 0.018) positions. There was no difference in HF/death by RV
      LV lead sub-groups. CONCLUSION: Among CRT-D patients, long-term outcomes were
      similar for non-apical RV and apical RV leads. However, mortality risk was
      increased with discordant RV and LV leads, when a non-apical RV lead was combined
      with an apical LV lead.

PMID- 29572716
TI  - Comparison of single-coil lead versus dual-coil lead of implantable cardioverter
      defibrillator on lead-related venous complications in a canine model.
AB  - PURPOSE: Dual- coil lead (DCL) of implantable cardioverter defibrillator (ICD) is
      preferred clinically in patients. However, it is related to higher risk of venous
      stenosis and thrombosis. The present study was done to compare the fibrosis and
      extraction of the leads between the single-coil lead (SCL) and DCL in animal
      models. METHODS: This was a chronic animal study with a follow-up duration of 6
      months. Twenty mongrel dogs were randomly divided into DCL group or SCL group.
      Venography was performed before the sacrifice to evaluate the venous stenosis in
      vivo. The maximum pulling-out tension of the ICD lead was measured by a
      tensometer. Hematoxylin-eosin stain and toluidine blue O stain were applied to
      show the pathological changes of the superior vena cava (SVC) to evaluate the
      fibrosis and the thickness of the SVC adjacent to the leads. RESULTS: The DCL
      group showed higher incidence of venous stenosis (OR = 31.5; 95% CI, 2.35-422.3;
      p = 0.005). It revealed increased tension to extract the leads in the DCL group
      (5.96 +/- 1.86 vs. 3.68 +/- 1.46 N, p = 0.027). The difference of venous wall
      thickness of SVC was 4.3 +/- 0.3 fold-changes between two groups (p = 0.007).
      Moreover, the degree of venous wall fibrosis in DCL group was more serious than
      that it in SCL group (3.61 +/- 1.26 vs. 1.08 +/- 1.35 mm2, p = 0.015).
      CONCLUSION: The DCL was proved to increase thrombosis, fibrosis, and stenosis in
      the SVC. Likewise, the DCL was mechanically harder to be extracted than the SCL.
      Our study showed that lead-related complications of the DCLs were higher than
      those of the SCLs regardless of the equal defibrillation thresholds between them.
      Results of the present study would help to choose the proper lead which could be
      removed.

PMID- 29572717
TI  - Ventricular arrhythmias originating from the cardiac crux and the basal inferior
      segment of the interventricular septum in the patients with structural heart
      diseases: characteristics, mapping, and electrophysiological properties.
AB  - PURPOSE: There are few reports describing ventricular arrhythmias (VAs) from the
      crux and the corresponding endocardial site, i.e., the basal inferior segment of
      the interventricular septum (IVS). We aimed to investigate a distinct clinical
      group of VAs arising from the endocardium at this area in patients with
      structural heart diseases (SHD). METHODS: We included 17 patients with SHD and
      clinically documented VAs. Thirteen patients underwent endocardial mapping only.
      Three patients underwent both epicardial and endocardial approaches and one had
      only epicardial mapping. Eighteen VAs were identified, 14 focal and 4 reentrant
      VAs, confirmed by entrainment. RESULTS: There were 2 VAs from the crux, 5 VAs
      from the corresponding endocardial site in the right ventricle (RV), and 11 from
      the site in the left ventricle (LV). Compared with the VAs from RV endocardium,
      VAs from LV endocardium had a higher R wave in V3 than V2 (V2R/V3R ratio, 1.83 +/
      0.84 vs. 0.86 +/- 0.38, P = 0.008) and a higher V3 transition ratio percentage
      (2.16 +/- 2.07 vs. 0.58 +/- 0.62, P = 0.008). Combining all 16 patients with
      endocardial mapping, there were also lower bipolar voltages (1.21 +/- 1.05 vs.
      3.10 +/- 2.65 mv, P < 0.0001), lower unipolar voltages (4.05 +/- 1.92 vs. 5.75 +/
      2.90 mv, P < 0.0001), and longer local electrocardiogram (EGM) lateness (157.6
      +/- 47.9 vs.140.3 +/- 52.5 ms, P = 0.0001) in the dominant chambers. CONCLUSIONS:
      In VAs from the crux and the corresponding endocardial site, the complete ECG
      V2R/V3R ratio and V3 transition ratio percentage could differentiate the VAs from
      the RV or LV endocardium. The lower unipolar, bipolar voltage mapping, and longer
      EGM lateness are helpful to identify the abnormal substrate in the endocardium in
      these patients.

PMID- 29572718
TI  - Disparities in maternal health services in sub-Saharan Africa.
AB  - OBJECTIVES: To examine the progress of and disparities in the provision of key
      maternal health services in the sub-Saharan Africa (SSA) region. METHODS: A time
      trend analysis of disparities in antenatal care (ANC) and skilled birth
      attendance (SBA) coverage in SSA over the last 25 years was conducted. The
      average values of each country's 5-year period data were used for analysis.
      Absolute and relative disparities were examined by time period, economic class,
      geographic group and clusters. Analysis of variance was used to compare
      progresses in coverage across time. RESULTS: Regional median ANC coverage and SBA
      increased by 8% points and 15% points, respectively, during the 25-year period.
      The rank score of SBA has shown significant improvement only in the recent
      period. A 33.3% disparity between ANC and SBA was observed in the most recent
      period. The relative disparity by economic class and cluster was higher for SBA
      than ANC coverage. CONCLUSIONS: The region showed improvement in both indicators
      across time. Regional disparity in ANC narrowed down while that of SBA remained
      high. These were mainly associated with economic class and cluster of countries.

PMID- 29572719
TI  - A Systematic Review of Studies Comparing the Measurement Properties of the Three
      Level and Five-Level Versions of the EQ-5D.
AB  - BACKGROUND: Since the introduction of the five-level version of the EQ-5D (5L),
      many studies have comparatively investigated the measurement properties of the
      original three-level version (3L) with the 5L version. OBJECTIVE: The aim of this
      study was to consolidate the available evidence on the performance of both
      instruments. METHODS: A systematic literature search of studies in the English
      and German languages was conducted (2007-January 2018) using the PubMed, EMBASE,
      and PsycINFO (EBSCO) databases, as well as the EuroQol Research Foundation
      website. Data were extracted and assessed on missing values, distributional
      properties, informativity indices (Shannon's H' and J'), inconsistencies,
      responsiveness, and test-retest reliability. RESULTS: Twenty-four studies were
      included in the review. Missing values and floor effects (percentage reporting
      the worst health state) were found to be negligible for both 3L and 5L (< 5%).
      From 18 studies, inconsistencies ranged from 0 to 10.6%, although they were
      generally well below 5%, with 9 studies reporting the most inconsistencies for
      Usual Activities (mean percentage 4.1%). Shannon's indices were always higher for
      5L than for 3L, and all but three studies reported lower ceiling effects
      ('11111') for 5L than for 3L. There is mixed and insufficient evidence on
      responsiveness and test-retest reliability, although results on index values
      showed better performance for 5L on test-retest reliability. CONCLUSION: Overall,
      studies showed similar or better measurement properties of the 5L compared with
      the 3L, and evidence indicated moderately better distributional parameters and
      substantial improvement in informativity for the 5L compared with the 3L.
      Insufficient evidence on responsiveness and test-retest reliability implies
      further research is needed.

PMID- 29572720
TI  - A 25-year retrospective analysis of the American Society of Anesthesiologists
      physical status classification: did we "up-code" young obese patients when
      obesity was not yet considered a disease?
AB  - PURPOSE: The influence of obesity on anesthetic risk remains controversial, and
      obesity has only recently been specifically identified as a criterion by which a
      patient can be given a higher American Society of Anesthesiologists-physical
      status (ASA-PS) score. Nevertheless, we hypothesized that clinicians had assigned
      obese patients a greater ASA-PS score before obesity became an "official"
      criterion in 2015. METHODS: Basic demographic and physical details were collected
      on patients receiving anesthetics in the Virginia Commonwealth University Health
      System between 1986 and 2010. The risk ratio (RR) of "up-coding" ASA-PS
      classification assignments was calculated for patients of varying body mass index
      (BMI). We specifically focused on the subset of patients aged 20-29 yr in whom
      the medical sequelae of obesity would not yet likely be manifest. RESULTS: Among
      a total of 194,698 patients, the percentage who were obese increased from 20% to
      39% between 1986 and 2010. Obese patients of all ages were more likely than non
      obese patients to be classified as ASA-PS II-IV rather than ASA-PS I. The RR and
      ratio of RR analyses indicated a consistent pattern of up-coding patients with
      greater BMI (contingency table Chi-square: P < 0.001). Most notably, relative to
      patients with a normal BMI, young obese patients aged 20-29 yr had an increased
      likelihood of up-coding in ASA-PS compared with obese patients in the older
      cohorts. CONCLUSIONS: These findings suggest a consistent and temporally stable
      practice of up-coding obese patients despite this lack of explicit guidance. The
      ASA House of Delegates' recent decision to specifically mention obesity
      reinforces long-existing practices regarding ASA-PS coding and will likely not
      degrade the validity of data sets collected before the change.

PMID- 29572721
TI  - Planning and navigation as active inference.
AB  - This paper introduces an active inference formulation of planning and navigation.
      It illustrates how the exploitation-exploration dilemma is dissolved by acting to
      minimise uncertainty (i.e. expected surprise or free energy). We use simulations
      of a maze problem to illustrate how agents can solve quite complicated problems
      using context sensitive prior preferences to form subgoals. Our focus is on how
      epistemic behaviour-driven by novelty and the imperative to reduce uncertainty
      about the world-contextualises pragmatic or goal-directed behaviour. Using
      simulations, we illustrate the underlying process theory with synthetic
      behavioural and electrophysiological responses during exploration of a maze and
      subsequent navigation to a target location. An interesting phenomenon that
      emerged from the simulations was a putative distinction between 'place cells'
      that fire when a subgoal is reached-and 'path cells'-that fire until a subgoal is
      reached.

PMID- 29572722
TI  - Fruit and Vegetable Intake: the Interplay of Planning, Social Support, and Sex.
AB  - PURPOSE: Intention and planning are important predictors of dietary change.
      However, little attention has been given yet to the relationship between them as
      a function of other social-cognitive factors and their interplay with socio
      demographics such as sex. METHODS: In an observational study (1520 women, 430
      men) with two measurement points in time, intention (predictor), planning
      (mediator), social support (first moderator), and sex (second moderator) were
      assessed to predict changes in diet separately for fruit and vegetable intake.
      RESULTS: All predictors had a main effect on fruit intake but no interactions
      emerged. For vegetable intake, the mediation-chain was qualified by a three-way
      interaction: for women, the lower the perceived social support, the more the
      translation of planning into behavior; for men, the higher the perceived social
      support, the more the translation of planning into behavior. CONCLUSIONS: Even
      though intention and planning are predictors of dietary change, they operate
      differently under specific conditions (level of social support), for specific
      subgroups (men vs. women), and for different target behaviors (fruit vs.
      vegetable intake). These results suggest to further examine the mechanisms by
      which intentions are translated into behavior via planning.

PMID- 29572724
TI  - Is BRCA Mutation Testing Cost Effective for Early Stage Breast Cancer Patients
      Compared to Routine Clinical Surveillance? The Case of an Upper Middle-Income
      Country in Asia.
AB  - OBJECTIVE: Previous studies showed that offering BRCA mutation testing to
      population subgroups at high risk of harbouring the mutation may be cost
      effective, yet no evidence is available for low- or middle-income countries
      (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing
      in early-stage breast cancer patients with high pre-test probability of
      harbouring the mutation in Malaysia, an LMIC in Asia. METHODS: We developed a
      decision analytic model to estimate the lifetime costs and quality-adjusted life
      years (QALYs) accrued through BRCA mutation testing or routine clinical
      surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer
      patients aged 40 years. In the model, patients would decide whether to accept
      testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen,
      combinations or neither. We calculated the incremental cost-effectiveness ratio
      (ICER) from the health system perspective. A series of sensitivity analyses were
      performed. RESULTS: In the base case, testing generated 11.2 QALYs over the
      lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost
      US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective
      thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA
      mutation testing and utility of being risk-free, but the ICERs remained below the
      thresholds. Probabilistic sensitivity analysis showed that at a threshold of
      US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.
      CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients
      identified using a locally-validated risk-assessment tool may be cost effective
      compared to RCS in Malaysia.

PMID- 29572725
TI  - Individual and Institutional Corruption in European and US Healthcare: Overview
      and Link of Various Corruption Typologies.
AB  - In recent years, the fight against healthcare corruption has intensified.
      Estimates from the European Healthcare Fraud and Corruption Network calculate an
      approximate ?56 billion annual loss to Europe as a result of corruption. To
      promote understanding of the complexity and interconnection of corrupt
      activities, we aim to present healthcare-related corruption typologies of the
      European Union and European Healthcare Fraud and Corruption Network. We
      subsequently link them to the typology of individual and institutional corruption
      introduced by Dennis Thompson in the context of investigating misconduct of US
      Congressional members. According to Thompson, individual corruption is the
      personal gain of individuals performing duties within an institution in exchange
      for nurturing private interests, while institutional corruption pertains to the
      failure of the institution in directing the individual's behaviour towards the
      achievement of the institution's primary purpose because the institutional design
      promotes the pursuit of individual goals. Effective anti-corruption activities
      not only require the enactment of anti-corruption laws but also the monitoring
      and, where appropriate, revision of institutional frameworks to prevent the
      undermining of the primary purposes of health systems or institutions. To gain
      further understanding of the similarities and differences of the three
      typologies, prime examples of corrupt activities in the health sector in the
      European Union and USA (along with their potential remedies) are provided.
      Linking corruption cases to Thompson's typology revealed that many corrupt
      activities may show elements of both individual and institutional corruption
      because they are intertwined, partly overlap and may occur jointly. Hence,
      sanctioning individual actors only does not target the problem.

PMID- 29572726
TI  - The evaluation of the effect of venous diameter measurement by ultrasonography on
      pain and withdrawal response.
AB  - PURPOSE: Rocuronium and propofol are used in the induction of anesthesia give
      discomfort to the patients. We aimed to investigate the relationship between
      venous diameter measured using ultrasonography, and pain and withdrawal movements
      after propofol and rocuronium applied with intravenous (IV). METHODS: This
      prospective-observational study was performed on 142 voluntary patients
      undergoing surgical operation under general anesthesia. An ultrasonography was
      used to measure the vein transverse diameter. Patients with a venous transverse
      diameter of <=2 mm were classified as group 1 (n = 50), while patients with a
      diameter of > 2 mm were classified as group 2 (n = 92). The propofol pain was
      assessed according to the verbal rating scale (VRS). In addition, the withdrawal
      movements of the rocuronium injection were evaluated using the four-point scale.
      RESULTS: There was no difference between the two groups in terms of the
      demographic data. The patients have pain after propofol 38.2% and withdrawal
      movements after rocuronium 42.4% were detected. The maximum number of patients
      without pain after propofol injection (78.2%) and without withdrawal movements
      after rocuronium (76%) was found to be higher in group 2 (p = 0.001). CONCLUSION:
      In this study, we found a reduction in the incidence and severity of pain and
      withdrawal movements in intravenous propofol and rocuronium administration
      through peripheral venous vessels of large diameter. We believe that the clinical
      drug injection through vessels with large venous diameter with the help of USG
      may be a non-invasive, simple, and reliable method to reduce pain and withdrawal
      movements in propofol and rocuronium injections.

PMID- 29572727
TI  - Should we rely on Doppler ultrasound for evaluation of testicular solid lesions?
AB  - PURPOSE: Colour Doppler ultrasound (CDUS) is the main radiologic tool to evaluate
      scrotal masses and intratesticular-vascularised solid lesions are mostly
      considered malign lesions. Objective of this trial is determine ratio of benign
      lesions in patients with hypervascularised solid intratesticular lesions.
      MATERIAL AND METHOD: Patients who underwent radical orchiectomy due to
      hypervascularised intratesticular solid lesions detected in CDUS are evaluated
      retrospectively. Those with previous testicular cancer history and
      inguinal/scrotal surgeries were excluded from the study. All patients are
      evaluated for age, preoperative testicular atrophy, multicentricity, echotexture
      and size of solid lesions, preoperative tumor markers (AFP, bHCG and LDH), and
      postoperative pathology results. Two tailed p value test was used to evaluate
      numeric parameters and Fisher's exact test was used to evaluate non-numeric
      parameters. RESULTS: A total of 117 patients with a mean age of 35.9 (5-86) were
      included to the study. Mean size of solid lesions was 4.39 cm. Seven patients had
      subcentimeter (subcm) lesions. 101 patients had hypoechoic, ten patients had
      isoechoic and six patients hyperechoic solid lesions. Preoperatively 60 patients
      (51.2%) had at least one tumor marker elevated. Postoperative pathology
      examination resulted to; 21 patients (17.9%) had benign lesions. Elevation of
      tumor markers, palpability, hypoechoic texture and larger size of the solid
      lesion were found to be parameters that predict malignancy. CONCLUSION: Benign
      incidence of vascular testicular solid lesions detected with scrotal ultrasound
      with colour Doppler is greater than expected. In patients with smaller, non
      palpable lesions without elevated tumor markers, treatment options other than
      radical orchiectomy such as testicular sparing surgery should be considered.

PMID- 29572728
TI  - 68Ga-labelled PSMA (prostate specific membrane antigen) expression in signet-ring
      cell gastric carcinoma.

PMID- 29572729
TI  - Decision-making for complex scapula and ipsilateral clavicle fractures: a review.
AB  - INTRODUCTION: Complex scapula with ipsilateral clavicle fracures remains a
      challange and treatment recommendations are still missing.  This review provides
      an overview of the evolution of the definition, classification and treatment
      strategies for complex scapula and ipsilateral clavicle fractures. As with other
      rare conditions, consensus has not been reached on the most suitable management
      strategies to treat these patients. The aim of this review is twofold: to compile
      and summarize the currently available literature on this topic, and to recommend
      treatment approaches. MATERIALS AND METHODS: Included in the review are the
      following topics: biomechanics of scapula and ipsilateral clavicle fractures,
      preoperative radiological evaluation, surgical treatment of the clavicle only,
      surgical treatment of both the clavicle and scapula, and nonsurgical treatment
      options. RESULTS: A decision-making algorithm is proposed for different treatment
      strategies based on pre-operative parameters, and an example of a case treated
      our institution is presented to illustrate use of the algorithm. DISCUSSION: The
      role of instability in complex scapula with ipsilateral clavicle fractures
      remains unclear. The question of stability is preoperatively less relevant than
      the question of whether the dislocated fragments lead to compromised shoulder
      function.

PMID- 29572730
TI  - Could resuscitative endovascular balloon occlusion of the aorta improve survival
      among severely injured patients with post-intubation hypotension?
AB  - Current literature shows the association of post-intubation hypotension and
      increased odds of mortality in critically ill non-trauma and trauma populations.
      However, there is a lack of research on potential interventions that can prevent
      or ameliorate the consequences of endotracheal intubation and thus improve the
      prognosis of trauma patients with post-intubation hypotension. This review paper
      hypothesizes that the deployment of REBOA among trauma patients with PIH, by its
      physiologic effects, will reduce the odds of mortality in this population. The
      objective of this paper is to review the current literature on REBOA and post
      intubation hypotension, and, furthermore, to provide a rational hypothesis on the
      potential role of REBOA in severely injured patients with post-intubation
      hypotension.

PMID- 29572731
TI  - DFT study of nano zinc/copper voltaic cells.
AB  - To facilitate the development of new materials for use in batteries, it is
      necessary to develop ab initio full-electron computational techniques for
      modeling potential new battery materials. Here, we tested density functional
      theory procedures that are accurate enough to obtain the energetics of a
      zinc/copper voltaic cell. We found the magnitude of the zero-point energy
      correction to be 0.01-0.2 kcal/mol per atom or molecule and the magnitude of the
      dispersion correction to be 0.1-0.6 kcal/mol per atom or molecule for Zn n ,
      (H2O) n , [Formula: see text], [Formula: see text], and Cu n . Counterpoise
      correction significantly affected the values of ?[Formula: see text], ?[Formula:
      see text], and ?Esolv by 1.0-3.1 kcal/mol per atom or molecule at the B3PW91/6
      31G(d) level of theory, but by only 0.04-0.4 kcal/mol per atom or molecule at the
      B3PW91/cc-pVTZ level of theory. The application of B3PW91/6-31G(d) yielded
      results that differed from macroscopic experimental values by 0.1-7.1 kcal/mol
      per atom or molecule, whereas applying B3PW91/cc-pVTZ produced results that
      differed from macroscopic experimental values by 0.1-4.8 kcal/mol per atom or
      molecule, with the smallest differences occurring for reactions with a small
      macroscopic experimental ?E and the largest differences occurring for reactions
      with a large macroscopic experimental ?E, implying size consistency.

PMID- 29572723
TI  - Thermodynamics in Neurodegenerative Diseases: Interplay Between Canonical
      WNT/Beta-Catenin Pathway-PPAR Gamma, Energy Metabolism and Circadian Rhythms.
AB  - Entropy production rate is increased by several metabolic and thermodynamics
      abnormalities in neurodegenerative diseases (NDs). Irreversible processes are
      quantified by changes in the entropy production rate. This review is focused on
      the opposing interactions observed in NDs between the canonical WNT/beta-catenin
      pathway and PPAR gamma and their metabolic and thermodynamic implications. In
      amyotrophic lateral sclerosis and Huntington's disease, WNT/beta-catenin pathway
      is upregulated, whereas PPAR gamma is downregulated. In Alzheimer's disease and
      Parkinson's disease, WNT/beta-catenin pathway is downregulated while PPAR gamma
      is upregulated. The dysregulation of the canonical WNT/beta-catenin pathway is
      responsible for the modification of thermodynamics behaviors of metabolic
      enzymes. Upregulation of WNT/beta-catenin pathway leads to aerobic glycolysis,
      named Warburg effect, through activated enzymes, such as glucose transporter
      (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1),
      monocarboxylate lactate transporter 1 (MCT-1), lactic dehydrogenase kinase-A (LDH
      A) and inactivation of pyruvate dehydrogenase complex (PDH). Downregulation of
      WNT/beta-catenin pathway leads to oxidative stress and cell death through
      inactivation of Glut, PKM2, PDK1, MCT-1, LDH-A but activation of PDH. In
      addition, in NDs, PPAR gamma is dysregulated, whereas it contributes to the
      regulation of several key circadian genes. NDs show many dysregulation in the
      mediation of circadian clock genes and so of circadian rhythms. Thermodynamics
      rhythms operate far-from-equilibrium and partly regulate interactions between
      WNT/beta-catenin pathway and PPAR gamma. In NDs, metabolism, thermodynamics and
      circadian rhythms are tightly interrelated.

PMID- 29572732
TI  - Efficacy and Safety of Sublingual Fentanyl Tablets in Breakthrough Cancer Pain
      Management According to Cancer Stage and Background Opioid Medication.
AB  - OBJECTIVE: Our objective was to assess the effect of sublingual fentanyl tablets
      (SFTs) on pain relief, quality of life, and adverse effects in patients with
      cancer pain, according to cancer stage and background opioid regimen. METHODS:
      Subgroup analyses from a recently completed study were performed according to
      cancer stage (locally advanced cancer [LAC] vs. metastatic cancer) and most
      frequent background opioid medication (fentanyl vs. oxycodone/naloxone). The
      efficacy and safety of SFTs were evaluated, recording pain intensity (PI), onset
      of pain relief, and adverse events (AEs). Health status was assessed with the
      Short Form 12, version 2 (SF-12v2) questionnaire and the Hospital Anxiety and
      Depression Scale (anxiety subscale [HADS-A] and depression subscale [HADS-D]).
      RESULTS: In total, 54 (67.5%) patients had LAC and 26 (32.5%) had metastatic
      cancer. The oxycodone/naloxone group included 39 patients (48.1%) and the
      fentanyl group 29 (35.8%). In all subgroups, pain relief was achieved within 5
      min in an increasing number of individuals over time; at the end of the study, PI
      values decreased (PI-end: 44.4% for LAC vs. 57.9% for metastatic cancer; 44.4%
      for fentanyl vs. 38.6% for oxycodone/naloxone). HADS and mental component summary
      (MCS) SF-12v2 scores significantly improved in the LAC group (HADS-A 9.44-8.04;
      HADS-D 10.46-8.15; MCS 44.69-45.94) and in the fentanyl group (HADS-A 10.05-8.33;
      HADS-D 11.95-8.76; MCS 44.38-47.19). AEs were reported in few patients and were
      mostly mild. CONCLUSIONS: Exploratory subgroup analyses show the efficacy and
      safety of SFTs for the treatment of breakthrough pain in patients with cancer,
      regardless of their cancer stage and background opioid medication.

PMID- 29572733
TI  - Williams Syndrome and Anesthesia for Non-cardiac Surgery: High Risk Can Be
      Mitigated with Appropriate Planning.
AB  - Patients with Williams syndrome are considered at high risk for anesthesia
      related adverse events. At our institution, all William syndrome patients
      undergoing cardiac surgical, cardiac catheterization/interventional procedures,
      and cardiac imaging studies are cared for by cardiac anesthesiologists. All
      William syndrome patients undergoing non-cardiac surgical, interventional, or
      imaging studies are cared for by main operating room pediatric anesthesiologists
      with consultative input from a cardiac anesthesiologist. We reviewed our
      experience with 75 patients undergoing 202 separate anesthetics for 95 non
      cardiac procedures and 107 cardiac procedures from 2012 to 2016. The mean age was
      7.5 +/- 7.0 years and the mean weight was 22.3 +/- 17.0 kg. One hundred and
      eighty-seven patients had a general anesthetic (92.6%). Medications used included
      etomidate in 26.2%, propofol in 37.6%, isoflurane in 47.5%, and sevoflurane in
      68.3%. Vasopressors and inotropes were required including calcium (22.8%),
      dopamine (10.4%), norepinephrine (17.3%), phenylephrine (35.1%), vasopressin
      (0.5%), and ephedrine (5.4%). The median length of stay after anesthesia was 2.8
      days (range 0-32). No adverse events occurred in 89.6% of anesthetics. There were
      two cases of cardiac arrest, one of which required extracorporeal life support
      for resuscitation. Of the non-cardiac surgical procedures, 95.7% did not have a
      cardiovascular adverse event. Patients with Williams syndrome are at high risk
      for anesthesia, especially when undergoing cardiac procedures. The risk can be
      mitigated with appropriate planning and adherence to the hemodynamic goals for
      non-cardiac surgical procedures.

PMID- 29572734
TI  - Health-related quality of life in adolescent and young adult cancer survivors.
AB  - PURPOSE: Today, survival rates for adolescent and young adult (AYA) cancer
      patients exceed 80%. However, cancer and treatment leave many patients suffering
      from chronic conditions. These late effects may impair their health-related
      quality of life (HRQoL). We aimed to (1) compare HRQoL of AYA cancer survivors
      with the Swiss general population and (2) investigate socio-demographic and
      cancer-related characteristics associated with poor HRQoL. METHODS: AYA cancer
      survivors (age 16-25 at diagnosis; >=5 years survival) who had been identified
      through the Cancer Registry Zurich and Zug, Switzerland, filled out a
      questionnaire. We assessed HRQoL using the Short-Form 12 (SF-12), producing two
      scores: Physical Component Summary score (PCS, physical health) and Mental
      Component Summary score (MCS, mental health). We used multivariable logistic
      regression analyses to investigate associated characteristics. RESULTS: We
      compared 155 survivors with 350 controls. Survivors had significantly lower
      physical health than controls (mean = 52.5 vs. mean = 54.7, p < 0.001). Male
      survivors reported better mental health than controls (55.2 vs.53.3, p = 0.078)
      and females slightly worse (49.8 vs. 51.8, p = 0.285). Poor physical health was
      strongly associated with having a migration background (OR = 4.63, p = 0.008) and
      unemployment (OR = 7.66, p = 0.005). Poor mental health was associated with
      female sex (OR = 2.69, p = 0.057), suffering from late effects (OR = 5.91, p <
      0.001) and a migration background (OR = 5.82, p = 0.004). CONCLUSIONS: Results
      emphasize the need for individualized support services to improve survivors'
      HRQoL in vulnerable subgroups. We recommend adapted care for women and migrants,
      in addition to educational and employment support systems.

PMID- 29572735
TI  - Correlation and differences in cervical sagittal alignment parameters between
      cervical radiographs and magnetic resonance images.
AB  - PURPOSE: Although cervical alignment is better assessed using standing
      radiography than supine magnetic resonance imaging (MRI), few studies have
      investigated this. This study aimed to investigate the difference in alignment
      between standing radiographs and supine MRI images, and assess whether neck
      position affects the cervical parameters and neurological changes. METHODS: We
      analyzed 53 patients, measuring the O-C2 angle, C2-7 angle (the distinction
      between the lordotic and kyphotic groups), T1 slope, neck tilt, thoracic inlet
      angle, and the C2-7 sagittal vertical axis. Inter- and intra-group analyses were
      conducted to identify any difference between standing radiography and supine MRI.
      Statistical differences between the cervical parameters were compared. RESULTS:
      Strong correlations were noted between the equivalent parameters in the
      radiographs and MRI images, whereas no significant difference was observed in C2
      7 angle in the kyphotic group between the radiographs and MRI images, or for neck
      tilt between the radiographs and MRI images. However, in the lordotic group, the
      C2-7 angle was significantly different between the two types of images and larger
      in the radiographs than in the MRI images (C2-7 angle in the radiographs: C2-7
      angle in the MRI images: 4.49 degrees , p < 0.001). CONCLUSIONS: Neck tilt was a
      constant parameter. The C2-7 angle in the kyphotic group was similar between the
      standing radiographs and the supine MRI images; however, the C2-7 angle in the
      lordotic group was different. Therefore, we recommend that standing cervical
      radiographs should be preoperatively obtained for all surgical patients. The
      slides can be retrieved under Electronic Supplementary Material.

PMID- 29572736
TI  - Anterior management of C2 fractures using miniplate fixation: outcome, function
      and quality of life in a case series of 15 patients.
AB  - PURPOSE: The classification systems by Anderson and D'Alonzo, Effendi, Benzel and
      others have limitations when it comes to morphologically categorising fractures
      of the second cervical vertebral body (C2) that present with or without an
      additional fracture of the dens or with or without an extension of the fracture
      line into the vertebral arch and displacement. Currently, there are no definitive
      recommendations for the treatment of fractures at the junction of the dens with
      the vertebral body of C2 on the basis of outcome and stability data. Depending on
      patient anatomy, either anterior or posterior approaches can be used to fuse C1
      and C2 and to achieve definitive surgical stabilisation. The anterior management
      of C2 fractures without C1-C2 fusion has the theoretical advantage that it
      preserves rotational motion at this motion segment and that the anterior approach
      is associated with lower morbidity. In the study presented here, we followed up a
      group of our patients who underwent anterior miniplate fixation for C2 fractures.
      METHODS: Fifteen patients underwent fixation of C2 fractures with titanium
      miniplates (Medartis Hand fixation system, 2.0 or 2.3 mm) that were placed using
      a submental approach. To our knowledge, this construct has not yet been described
      in the literature. Where necessary, this procedure was combined with screw
      fixation of the dens as described by Bohler. We retrospectively analysed
      operative reports and medical records, evaluated the patients' health status
      using the Short Form (36) Health Survey (SF-36), and performed clinical follow-up
      examinations. RESULTS: From January 2009 to June 2015, 226 traumatic lesions of
      the cervical spine were managed at our institution in the inpatient setting.
      Ninety-two patients underwent conservative treatment. Of the 134 cases that
      required surgery for fractures and instability, 67 involved the C0-C3 motion
      segments. In 15 patients, stability was achieved using an anterior miniplate or
      miniscrews alone (n = 4) or in addition to other techniques (n = 11). Anderson
      and D'Alonzo type II and III dens fractures with involvement of the body or
      lateral mass of C2 accounted for eight cases. Effendi type II body fractures with
      or without instability were seen in four cases. There was no perioperative
      mortality and morbidity in this patient group. All fractures healed and stability
      was achieved in all cases. No patient had neurological deficits or required
      revision surgery. An assessment of postoperative quality of life showed that 11
      patients (7 men, 4 women) with a mean age of 57 (+/- 5.3) years reached an SF-36
      score that was normal for their age group after a mean period of 33 (+/- 6.3)
      months following their injury. Compared to a group of healthy subjects, the
      patients had a range of motion that was limited only at the extremes.
      CONCLUSIONS: In patients with appropriate indications, anterior fixation with
      miniplates alone or additionally is a further useful treatment option in the
      management of fractures at the junction of the dens with the vertebral body of
      C2. Since this type of treatment preserves motion at the C1-C2 motion segment
      after fracture healing and since an anterior approach is associated with less
      surgical trauma than posterior instrumentation, the technique presented here
      should be included in a discussion on (surgical) treatment options. These slides
      can be retrieved under Electronic Supplementary Material.

PMID- 29572737
TI  - Letter to the Editor concerning "Primary intramedullary hydatid cyst: a case
      report and literature review" by Zhang Z, Fan J, Dang Y, Xu R, Shen C (2017) Eur
      Spine J 26(Suppl 1):107-110.

PMID- 29572738
TI  - Staged insertion of growing rods in severe scoliosis.
AB  - PURPOSE: The objective of this retrospective chart and radiographic review was to
      present the clinical outcomes and complication rate of a staged approach to
      modern dual growing-rod (GR) surgery when treating children with severe early
      onset scoliosis. METHODS: Fifteen patients received a 6-mm dual GR system. During
      Stage 1, pairs of end vertebra were exposed in a subperiosteal fashion,
      instrumented, grafted, and fused. Stage 2 was performed, on average, 5 months
      later (range 8-35 weeks) and the fused foundations were connected with two
      growing rods under skull-femoral traction. Clinical and operative notes were
      reviewed and all complications were recorded. Radiographic measurements were
      assessed at pre-index, with intraoperative traction during Stage 1, post-Stage 2
      and at most recent follow-up. Statistical analyses were performed to evaluate
      change in scoliosis and kyphosis. RESULTS: At initial surgery, the average age
      was 8.17 +/- 1.5 years. The mean Cobb angle was 88.1 degrees  +/- 14.0 degrees ,
      corrected to 60.3 degrees  +/- 8.7 degrees  (p < 0.001) with intraoperative
      traction in Stage 1, preserved after Stage 2 instrumentation (59.5 degrees  +/-
      9.6 degrees , p = 0.69), and maintained with subsequent lengthenings (60.6
      degrees  +/- 12.8 degrees , p = 0.73). Hyperkyphosis (11/15 patients) improved
      from 70.8 degrees  +/- 15.7 degrees  to 46.6 degrees  +/- 9.7 degrees  (p <
      0.001). At minimum 2-year follow-up (range 24-80 months, mean 49.5), the
      complication rate was 14 (0.93 complications/patient), including 6 rod breakages,
      6 superficial infections, and 2 deep infections. No anchor migration or pull-out
      was noted. Seven patients have undergone definitive posterior spinal fusion.
      CONCLUSIONS: Staged insertion of dual GR systems permits strong distraction, with
      acceptable correction of severe deformities and minimal complications. These
      slides can be retrieved under Electronic Supplementary Material.

PMID- 29572739
TI  - Timing of surgery in traumatic spinal cord injury: a national, multidisciplinary
      survey.
AB  - PURPOSE: The optimal surgical timeframe for neurological recovery in traumatic
      spinal cord injury (tSCI) still remains unknown. Recent guidelines have
      recommended performing surgery within 24 h for all patients with tSCI regardless
      of initial neurological deficit. It remains unclear whether patients with
      complete, incomplete tSCI, or traumatic central cord injury (TCCI) will
      experience the same degree of improvement after urgent surgical intervention. We
      investigated if the severity of initial neurological injury influenced surgeons
      on their decision-making of surgical timing in tSCI. METHODS: With a web-based
      survey, we investigated the current opinion in The Netherlands on timing of
      surgical decompression and stabilization, depending on the initial degree of
      neurological injury. RESULTS: Surgeons prefer to perform more urgent surgery for
      incomplete tSCI compared to complete tSCI. In addition, 43% of patients with
      complete tSCI are not preferably operated within the recommended 24 h. Even
      though TCCI is the most common form of incomplete tSCI, these patients are
      preferably managed less urgently than patients with other types of incomplete
      tSCI. CONCLUSION: The severity of initial neurological injury seems to play an
      important role in the urgency of surgical timing for tSCI. A substantial number
      of patients with complete tSCI are not preferably treated within the recommended
      surgical timeframe, while patients with incomplete tSCI are preferably operated
      far more urgent than recommended in the current guidelines. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29572740
TI  - National Green Tribunal of India-an observation from environmental judgements.

PMID- 29572741
TI  - Active methods of mercury removal from flue gases.
AB  - Due to its adverse impact on health, as well as its global distribution, long
      atmospheric lifetime and propensity for deposition in the aquatic environment and
      in living tissue, the US Environmental Protection Agency (US EPA) has classified
      mercury and its compounds as a severe air quality threat. Such widespread
      presence of mercury in the environment originates from both natural and
      anthropogenic sources. Global anthropogenic emission of mercury is evaluated at
      2000 Mg year-1. According to the National Centre for Emissions Management (Pol.
      KOBiZE) report for 2014, Polish annual mercury emissions amount to approximately
      10 Mg. Over 90% of mercury emissions in Poland originate from combustion of
      coal.The purpose of this paper was to understand mercury behaviour during sub
      bituminous coal and lignite combustion for flue gas purification in terms of
      reduction of emissions by active methods. The average mercury content in Polish
      sub-bituminous coal and lignite was 103.7 and 443.5 MUg kg-1. The concentration
      of mercury in flue gases emitted into the atmosphere was 5.3 MUg m-3 for sub
      bituminous coal and 17.5 MUg m-3 for lignite. The study analysed six low-cost
      sorbents with the average achieved efficiency of mercury removal from 30.6 to
      92.9% for sub-bituminous coal and 22.8 to 80.3% for lignite combustion. Also, the
      effect of coke dust grain size was examined for mercury sorptive properties. The
      fine fraction of coke dust (CD) adsorbed within 243-277 MUg Hg kg-1, while the
      largest fraction at only 95 MUg Hg kg-1. The CD fraction < 0.063 mm removed
      almost 92% of mercury during coal combustion, so the concentration of mercury in
      flue gas decreased from 5.3 to 0.4 MUg Hg m-3. The same fraction of CD had
      removed 93% of mercury from lignite flue gas by reducing the concentration of
      mercury in the flow from 17.6 to 1.2 MUg Hg m-3. The publication also presents
      the impact of photochemical oxidation of mercury on the effectiveness of Hg
      vapour removal during combustion of lignite. After physical oxidation of Hg in
      the flue gas, its effectiveness has increased twofold.

PMID- 29572742
TI  - Detection of the natural origin hydrocarbon contamination in carbonate aquifers
      (central Apennine, Italy).
AB  - The water-rock interaction is discussed in this study for some Central Apennine
      aquifers and their relative springs, where the geological and hydrogeological
      setting is potentially responsible for hydrocarbon contamination. The
      contamination is related to the presence of limestone formations with high
      organic content that are connected to the genesis of hydrocarbons in the Central
      Southern Apennines. Thanks to a multidisciplinary approach based on a seasonal
      monitoring of hydrogeological, hydrogeochemical, organic chemical, and isotopic
      variables, and to a detailed geological analysis, it was possible to demonstrate
      that the bituminous schists within the bituminous dolomite formation (a Triassic
      Formation presents in the Gran Sasso acquifer), the bituminous intercalations
      within the Bolognano Formation (an Olocenic calcareous Formation in the Majella
      acquifer), and the petroleum-saturated rocks of the Bolognano Formation (in the
      Morrone acquifer) are all able to leach hydrocarbons into groundwater. The
      results suggest that more detailed studies are required for areas where
      lithologies with fossil organic components are present. Insights should further
      investigate the interaction between groundwater and rocks in terms of organic
      compounds as well as inorganic compounds. In particular, the study also suggests
      that the supplementary quantification of hydrocarbon compounds in bituminous rock
      and the leaching tests are analyses that provide reliable results. From the
      normative point of view, the results of the study can be useful when dealing with
      hydrocarbon contamination resulting from anthropogenic activities within
      catchments where formations with high concentration of organic matter are
      present. In these cases, it will possible to assess the natural background
      concentrations and review the threshold values upwards.

PMID- 29572743
TI  - Comparing ordinary kriging and inverse distance weighting for soil as pollution
      in Beijing.
AB  - Spatial interpolation method is the basis of soil heavy metal pollution
      assessment and remediation. The existing evaluation index for interpolation
      accuracy did not combine with actual situation. The selection of interpolation
      methods needs to be based on specific research purposes and research object
      characteristics. In this paper, As pollution in soils of Beijing was taken as an
      example. The prediction accuracy of ordinary kriging (OK) and inverse distance
      weighted (IDW) were evaluated based on the cross validation results and spatial
      distribution characteristics of influencing factors. The results showed that,
      under the condition of specific spatial correlation, the cross validation results
      of OK and IDW for every soil point and the prediction accuracy of spatial
      distribution trend are similar. But the prediction accuracy of OK for the maximum
      and minimum is less than IDW, while the number of high pollution areas identified
      by OK are less than IDW. It is difficult to identify the high pollution areas
      fully by OK, which shows that the smoothing effect of OK is obvious. In addition,
      with increasing of the spatial correlation of As concentration, the cross
      validation error of OK and IDW decreases, and the high pollution area identified
      by OK is approaching the result of IDW, which can identify the high pollution
      areas more comprehensively. However, because the semivariogram constructed by OK
      interpolation method is more subjective and requires larger number of soil
      samples, IDW is more suitable for spatial prediction of heavy metal pollution in
      soils.

PMID- 29572744
TI  - Ameliorative effects of nano-elemental selenium against hexavalent chromium
      induced apoptosis in broiler liver.
AB  - The current study examined the ameliorative effects of nano-elemental selenium
      (Nano-Se) against chromium-VI (K2Cr2O7)-induced apoptosis in chickens. The
      expression of apoptosis-related genes was evaluated by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and western blot. A total of 60,
      one-day-old broiler chickens allotted to six equal groups, i.e., control group
      (standard diet), Cr(VI)-exposed group (K2Cr2O7 via drinking water), Nano-Se group
      (Nano-Se at 0.5 mg/kg via diet), protection group (K2Cr2O7 + Nano-Se), cure group
      (K2Cr2O7 for initial 2 weeks and then Nano-Se), and prevention group (opposite to
      the cure group) and were detected by the activities of pro-apoptosis (Bax,
      Caspase-3) and anti-apoptosis (Bcl-2) genes expression at day 35 of the
      experiment. Intense apoptosis was observed in liver tissues of chickens exposed
      to K2Cr2O7. The Nano-Se supplementation caused a significant decrease (P < 0.01)
      in the mRNA expression levels of Bax and Caspase-3 genes, while significantly
      elevated (P < 0.05) mRNA expression level of Bcl-2 gene was observed in Nano-Se
      experimental groups as compare to control and Cr(VI)-exposed group. The results
      quantified by the RT-qPCR were further confirmed by the western blot analysis.
      Altogether, these results suggest anti-apoptotic effects of Nano-Se in the
      chicken liver, which is interesting for further study. The present findings
      suggested that Nano-Se has protective effects against K2Cr2O7-induced apoptosis
      in broilers liver and can serve a key role as a protective agent against
      apoptosis.

PMID- 29572745
TI  - Assessment of neurohepatic DNA damage in male Sprague-Dawley rats exposed to
      organophosphates and pyrethroid insecticides.
AB  - The current work was undertaken to test the genotoxic potential of chlorpyrifos
      (CPF), dimethoate, and lambda cyhalothrin (LCT) insecticides in rat brain and
      liver using the single cell gel electrophoresis (comet assay). Three groups of
      adult male Sprague-Dawley rats were exposed orally to one third LD50of CPF,
      dimethoate, or LCT for 24 and 48 h while the control group received corn oil.
      Serum samples were collected for estimation of malondialdehyde (MDA) and
      glutathione peroxidase (GPx); the brain and liver samples were used for comet
      assay and for histopathological examination. Results showed that signs of
      neurotoxicity appeared clinically as backward stretching of hind limb and splayed
      gait in dimethoate and LCT groups, respectively. CPF, LCT, and dimethoate induced
      oxidative stress indicated by increased MDA and decreased GPx levels. CPF and LCT
      caused severe DNA damage in the brain and liver at 24 and 48 h indicated by
      increased percentage of DNA in tail, tail length, tail moment, and olive tail
      moment. Dimethoate induced mild DNA damage in the brain and liver at 48 h.
      Histopathological changes were observed in the cerebrum, cerebellum, and liver of
      exposed rats. The results concluded that CPF, LCT, and dimethoate insecticides
      induced oxidative stress and DNA damage associated with histological changes in
      the brain and liver of exposed rats.

PMID- 29572746
TI  - Computed tomography pulmonary vascular volume ratio in children and young adults
      with congenital heart disease: the effect of cardiac phase.
AB  - BACKGROUND: The effect of cardiac phase on CT pulmonary vascular volumetry is
      unknown. OBJECTIVE: To evaluate the effect of cardiac phase on CT pulmonary
      vascular volume ratio in children and young adults with congenital heart disease.
      MATERIALS AND METHODS: Thirty-one children and young adults (median age 14 years)
      with congenital heart disease underwent electrocardiography-synchronized
      cardiothoracic CT at the end-systolic and end-diastolic phases as well as lung
      perfusion scintigraphy (n=20) or cardiac MRI (n=11). The author calculated right
      and left pulmonary vascular volumes by using threshold-based CT volumetry. Right
      pulmonary vascular volume percentages measured by CT obtained at the end-systolic
      and end-diastolic phases were compared with corresponding values measured by the
      reference method (lung perfusion scintigraphy or phase-contrast MRI) by using
      paired t-test and Bland-Altman analysis. RESULTS: The right pulmonary vascular
      volume percentages measured by CT were significantly greater at the end-systolic
      phase than at the end-diastolic phase (64.0+/-14.1% vs. 61.9+/-10.7%; P<0.01).
      The end-systolic CT right pulmonary vascular volume percentages were not
      significantly different from the corresponding values measured by the reference
      method (64.0+/-14.1% vs. 65.3+/-13.6%; P>0.05), while the end-diastolic vascular
      volume percentages were significantly smaller than the corresponding values
      measured by the reference method (61.9+/-10.7% vs. 65.3+/-13.6%; P=0.01). Bland
      Altman analysis showed a mean difference of 1.4+/-7.2% for the end-systolic CT,
      which was significantly smaller than that for the end-diastolic CT (3.4+/-7.0%;
      P<0.01). CONCLUSION: The CT pulmonary vascular volume ratio is significantly
      influenced by the cardiac phase of cardiothoracic CT. The end-systolic phase
      offers more accurate CT pulmonary vascular volumes than the end-diastolic phase.

PMID- 29572747
TI  - Severe nasomaxillary hypoplasia (Binder phenotype) on prenatal US/MRI: an
      important marker for the prenatal diagnosis of chondrodysplasia punctata.
AB  - BACKGROUND: Chondrodysplasia punctata is a skeletal dysplasia caused by a diverse
      spectrum of etiologies, with outcomes ranging from antenatal demise to a normal
      life span. Prenatal detection can be challenging. OBJECTIVE: To review a series
      of cases of chondrodysplasia punctata associated with nasomaxillary hypoplasia,
      known as the Binder phenotype, and to highlight prenatal ultrasound and MRI
      findings, as well as postnatal MRI and radiographic findings. MATERIALS AND
      METHODS: We retrospectively reviewed ultrasound, MRI and radiographic imaging
      findings in postnatally confirmed cases of chondrodysplasia punctata from 2001 to
      2017. We analyzed prenatal findings and correlated them with maternal history,
      postnatal imaging, phenotype, genetics and outcome. RESULTS: We identified eight
      cases, all with prenatal US and six of eight with prenatal MRI between 18 weeks
      and 32 weeks of gestational age. Reasons for referral included midface hypoplasia
      in four cases; family history in one case; intrauterine growth restriction in one
      case; short long-bones, intrauterine growth restriction and multicystic kidney in
      one case; and multiple anomalies in one case. In six cases, postnatal radiographs
      were performed. In four cases, postnatal spine MRI imaging was performed. The
      diagnosis of chondrodysplasia punctata was suggested in prenatal reports in six
      of eight fetuses. Seven of eight fetuses had Binder phenotype with severe
      nasomaxillary hypoplasia. Limb length was mildly symmetrically short in four of
      eight cases and normal in four of eight fetuses. Two of eight fetuses had
      epiphyseal stippling identified prenatally by US; this was present postnatally in
      six neonates on radiographs. Hand and foot abnormalities of brachytelephalangy
      were not detected on the prenatal US or MRI but were present in six of eigth
      fetuses on postnatal radiographs or physical exam. Four of eight fetuses had
      prenatal spine irregularity on US from subtle stippling. Six of eight had spine
      stippling on postnatal radiographs. One fetus had cervicothoracic kyphosis on
      prenatal US and MRI, and this was postnatally present in one additional neonate.
      One case had prenatally suspected C1 spinal stenosis with possible cord
      compression, and this was confirmed postnatally by MRI. There was a maternal
      history of systemic lupus erythematosus in two and hyperemesis gravidarum in one.
      Outcomes included one termination and seven survivors. CONCLUSION:
      Chondrodysplasia punctata can be identified prenatally but findings are often
      subtle. The diagnosis should be considered when a fetus presents with a
      hypoplastic midface known as the Binder phenotype. Maternal history of lupus, or
      other autoimmune diseases or hyperemesis gravidarum can help support the
      diagnosis.

PMID- 29572748
TI  - The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of
      endometriosis.
AB  - PURPOSE: The purpose of the work was to evaluate possible associations between
      the complement components C1q, mannose-binding lectin (MBL) and C1 inhibitor
      (C1INH) with pathogenesis of endometriosis. METHODS: Concentrations of C1q, MBL
      and C1INH were measured by ELISA in peritoneal fluid (PF) in 80 women with or
      without endometriosis. RESULTS: Significantly higher PF levels of C1q, MBL and
      C1INH in women with endometriosis compared to control group were observed (p <
      0.0001). A higher concentration of the studied parameter was found in PF of women
      at the early stage of the disease, as compared to women with advanced
      endometriosis (p < 0.0001). CONCLUSIONS: Our research suggests that in the
      peritoneal cavity in women with endometriosis there are abnormal regulations of
      both the classical and lectin pathways of the complement system. This can suggest
      impairments in purification of peritoneal cavity from ectopic endometrial cells
      and augmented local inflammation in endometriosis patients.

PMID- 29572750
TI  - The size of the renal artery orifice contributes to laterality of acute renal
      infarction.
AB  - BACKGROUND: Acute renal infarction (ARI) is a rare disease with atrial
      fibrillation being its main cause. The possible laterality of ARI is
      controversial. This study aimed to evaluate the association between anatomical
      features of the renal arteries and ARI. METHODS: This was a single-center cross
      sectional study that evaluated the anatomical and clinical features of renal
      arteries. The anatomical features of the renal arteries were assessed using
      computed tomography. RESULTS: A total of 46 patients (mean age 71.3 +/- 14.0
      years; men, 59%) were enrolled. ARI involved the left kidney in 63%, right kidney
      in 28%, and both kidneys in 9% of patients. The right renal artery orifice was
      often higher than that of the left renal artery (71%). The angle of divergence
      from the abdominal aorta was similar on both sides. The left renal artery orifice
      was larger than that of the right (83 +/- 24, 72 +/- 24 mm2; p = 0.03,
      respectively). A larger left orifice was present in 72% of all cases. ARI
      involved the side with the larger orifice in 64% of patients. CONCLUSION: The
      size of the renal artery orifice may be a factor that contributes to the
      laterality of ARI. Assessment of anatomical features is important when
      considering the laterality of the disease.

PMID- 29572749
TI  - Eculizumab treatment in severe pediatric STEC-HUS: a multicenter retrospective
      study.
AB  - BACKGROUND: Hemolytic uremic syndrome related to Shiga-toxin-secreting
      Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney
      injury in young children. No specific treatment has been validated for this
      severe disease. Recently, experimental studies highlight the potential role of
      complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody
      against terminal complement complex, has been used in severe STEC-HUS patients,
      mostly during the 2011 German outbreak, with conflicting results. METHODS: On
      behalf of the French Society of Pediatric Nephrology, we retrospectively studied
      33 children from 15 centers treated with EC for severe STEC-HUS. Indication for
      EC was neurologic involvement in 20 patients, cardiac and neurologic involvement
      in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical
      status at last follow-up, patients were divided into two groups: favorable (n =
      15) and unfavorable outcomes (n = 18). RESULTS: Among patients with favorable
      outcome, 11/14 patients (79%) displayed persistent blockade of complement
      activity before each EC reinjection. Conversely, in patients with unfavorable
      outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients
      presenting neurological symptoms, 19 had favorable neurological outcome including
      17 with prompt recovery following first EC injection. Only two adverse effects
      potentially related to EC treatment were reported. CONCLUSIONS: Taken together,
      these results may support EC use in severe STEC-HUS patients, especially those
      presenting severe neurological symptoms. The study, however, is limited by
      absence of a control group and use of multiple therapeutic interventions in
      treatment groups. Thus, prospective, controlled trials should be undertaken.

PMID- 29572751
TI  - Operator Experience and Outcomes After Left Main Percutaneous Coronary
      Intervention.
AB  - PURPOSE OF REVIEW: This review was performed with the goal of summarizing the
      role of operator experience in the treatment of severe left main stenosis by
      percutaneous intervention techniques. RECENT FINDINGS: The Evaluation of XIENCE
      versus Coronary Artery Bypass Surgery for Effectiveness of Left Main
      Revascularization (EXCEL) trial demonstrated that percutaneous coronary
      intervention and coronary artery bypass grafting had similar clinical outcomes
      for severe left main disease. However, PCI of the left main coronary stenosis is
      considered to be a high-risk intervention because of the large area of myocardium
      at jeopardy that can quickly cause hemodynamic compromise. Operator experience
      and familiarity with the use of hemodynamic support devices, plaque modification
      techniques, and intravascular imaging tools is associated with better clinical
      outcomes. In patients with severe left main stenosis undergoing percutaneous
      coronary intervention by high-volume operators, the clinical outcomes are
      superior.

PMID- 29572752
TI  - Development of a Smart Mobile Data Module for Fetal Monitoring in E-Healthcare.
AB  - The fetal heart rate (FHR) is a marker of fetal well-being in utero (when
      monitoring maternal and/or fetal pathologies) and during labor. Here, we
      developed a smart mobile data module for the remote acquisition and transmission
      (via a Wi-Fi or 4G connection) of FHR recordings, together with a web-based
      viewer for displaying the FHR datasets on a computer, smartphone or tablet. In
      order to define the features required by users, we modelled the fetal monitoring
      procedure (in home and hospital settings) via semi-structured interviews with
      midwives and obstetricians. Using this information, we developed a mobile data
      transfer module based on a Raspberry Pi. When connected to a standalone fetal
      monitor, the module acquires the FHR signal and sends it (via a Wi-Fi or a 3G/4G
      mobile internet connection) to a secure server within our hospital information
      system. The archived, digitized signal data are linked to the patient's
      electronic medical records. An HTML5/JavaScript web viewer converts the digitized
      FHR data into easily readable and interpretable graphs for viewing on a computer
      (running Windows, Linux or MacOS) or a mobile device (running Android, iOS or
      Windows Phone OS). The data can be viewed in real time or offline. The
      application includes tools required for correct interpretation of the data
      (signal loss calculation, scale adjustment, and precise measurements of the
      signal's characteristics). We performed a proof-of-concept case study of the
      transmission, reception and visualization of FHR data for a pregnant woman at 30
      weeks of amenorrhea. She was hospitalized in the pregnancy assessment unit and
      FHR data were acquired three times a day with a Philips Avalon(r) FM30 fetal
      monitor. The prototype (Raspberry Pi) was connected to the fetal monitor's RS232
      port. The emission and reception of prerecorded signals were tested and the web
      server correctly received the signals, and the FHR recording was visualized in
      real time on a computer, a tablet and smartphones (running Android and iOS) via
      the web viewer. This process did not perturb the hospital's computer network.
      There was no data delay or loss during a 60-min test. The web viewer was tested
      successfully in the various usage situations. The system was as user-friendly as
      expected, and enabled rapid, secure archiving. We have developed a system for the
      acquisition, transmission, recording and visualization of RCF data. Healthcare
      professionals can view the FHR data remotely on their computer, tablet or
      smartphone. Integration of FHR data into a hospital information system enables
      optimal, secure, long-term data archiving.

PMID- 29572754
TI  - Development of Whey Protein Concentrate-Pectin-Alginate Based Delivery System to
      Improve Survival of B. longum BL-05 in Simulated Gastrointestinal Conditions.
AB  - Bifidobacterium longum BL-05 encapsulated beads were developed by using whey
      protein concentrate (WPC) and pectin (PE) as encapsulating material through
      extrusion/ionic gelation technique with the objective to improve survival of
      probiotics in harsh gastrointestinal conditions. B. longum BL-05 was grown in MRS
      (de man rogosa and sharpe) broth, centrifuged and mixed with polymeric gel
      solution. Bead formulations E4 (2.5% WPC + 1.5% PE) and E5 (2% PE) showed the
      highest value for encapsulation efficiency, size, and textural properties
      (hardness, cohesiveness, springiness) due to increasing PE concentration. The
      survivability and viability of free and encapsulated B. longum BL-05 was assessed
      through their resistance to simulated gastric juice (SGJ), tolerance to bile
      salt, release profile in simulated intestinal fluid (SIF), and storage stability
      during 28 days at 4  degrees C. The microencapsulation provided protection to B.
      longum BL-05 and encapsulated cells were exhibited significant (p < 0.05)
      resistance to SGJ and SIF as compared to free cells. Bead formulations E3 (5.0%
      WPC + 1.0% PE) and E4 (2.5% WPC + 1.5% PE) exhibited more resistance to SGJ (at
      pH 2 for 2 h) and at 2% bile salt solution but comparatively slow release as
      compared to other bead formulations. Free cells lost their viability when stored
      at 4  degrees C after 28 days but microencapsulated cells demonstrated promising
      results during storage and viable cell count was > 107 CFU/g. This study revealed
      that extrusion using WPC and PE as encapsulating material could be considered as
      one of the novel technologies for protection and effective delivery of
      probiotics.

PMID- 29572753
TI  - How Do We Approach Benign Proliferative Lesions?
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize recently published
      literature addressing atypical ductal hyperplasia (ADH), lobular neoplasia
      (atypical lobular hyperplasia [ALH] and classic lobular carcinoma in situ [C
      LCIS]), non-classic lobular carcinoma in situ (NC-LCIS), papillary lesions, and
      flat epithelial atypia (FEA). RECENT FINDINGS: While ADH, ALN, and C-LCIS are
      well-established markers of an increased risk of future breast cancers, the risk
      implications are less clear for papillary lesions and FEA. NC-LCIS is the least
      well-characterized lesion, with scant published literature on its natural history
      and surgical management when encountered on needle biopsy. Recent data suggest
      that lobular neoplasia on core biopsy of a BI-RADS <= 4 concordant lesion does
      not require an excision, while ADH, atypical papillomas, and NC-LCIS should be
      excised. Evidence on FEA and papillomas without atypia suggests a low risk of
      upgrade on excision, and prospective studies on the upgrade of these lesions are
      ongoing.

PMID- 29572755
TI  - Optimization of Nutrient Composition for Producing ACE Inhibitory Peptides from
      Goat Milk Fermented by Lactobacillus bulgaricus LB6.
AB  - Hypertension is a serious threat to human health and food-derived angiotensin
      converting enzyme (ACE; EC 3.4.15.1) inhibitory peptides can be used to regulate
      high blood pressure without side effects. The composition of the nutrient medium
      for the production of these peptides by fermenting goat milk with Lactobacillus
      bulgaricus LB6 was optimized to increase the ACE inhibitory activity by Box
      Behnken design (BBD) of response surface methodology (RSM) in the present study.
      Soybean peptone, glucose, and casein had significant effects on both ACE
      inhibition rate and viable counts of L. bulgaricus LB6 during incubation. The
      results showed that the maximum values of ACE inhibition rate and viable counts
      for L. bulgaricus LB6 were reaching to 86.37 +/- 0.53% and 8.06 * 107 under the
      optimal conditions, which were 0.35% (w/w) soybean peptone, 1.2% (w/w) glucose,
      and 0.15% (w/w) casein. The results were in close agreement with the model
      prediction. The optimal values of the medium component concentrations can be a
      good reference for obtaining ACE inhibitory peptides from goat milk.

PMID- 29572756
TI  - Contamination by lead in sediments at Toledo River, hydrographic basin of PARANA
      III.
AB  - Due to intense agricultural and industrial activities, the environment has been
      affected by increasing amounts of pollutants, such as lead, a toxic heavy metal.
      When introduced to the environment, toxic metals are distributed and incorporated
      into the liquid medium, sediments, and aquatic biota; bioaccumulating. This
      research aimed to identify and quantify the levels of toxic metals present in the
      waters and sediments of Toledo River, compare the obtained results with
      legislation and other studies, as well as to evaluate the possible pollutant
      sources of the water body. Six water and sediment samples were taken at seven
      strategic sites. The concentrations of Cu, Zn, Fe, Mn, Cd, Pb, and Cr in water
      were compared to the maximum limits established by Brazilian legislation IN
      CONAMA No. 357/05, for class II fresh waters. The sediment samples were submitted
      to nitroperchloric digestion, and then the total concentrations of the metals
      were determined by flame atomic absorption spectrometry (FAAS). The toxicological
      quality of the Toledo River has been considerably affected by the activities
      carried out in its surroundings, such as extensive areas of agriculture, pig
      farming and industrial areas, causing concentrations of Cd, Fe, and mainly Pb,
      which is observed at concentrations higher than value allowed by the legislation.

PMID- 29572757
TI  - [Pain is modality-specific : Differences in the perception and processing of
      interoceptive visceral compared to exteroceptive cutaneous heat pain stimuli].
AB  - Interoceptive visceral pain is perceived as more fear-inducing and unpleasant
      compared to cutaneous heat pain in healthy women even when stimuli are matched
      for perceived pain intensity. On a neural level, both pain stimuli induce
      comparable neural activation in areas related to processing of sensory
      discriminative pain aspects. However, enhanced neural responses are observed in
      areas associated with salience processing and descending pain inhibition for the
      visceral pain modality, even when results are controlled for intra-individual
      differences in perceived pain intensity. Moreover, immanent fear of pain is
      suggested to play a distinctive role in perception of visceral pain.

PMID- 29572758
TI  - Does freedom make a difference? : An empirical investigation of differences
      between subjective well-being and perceived capabilities amongst cancer patients.
AB  - Perceived capabilities-a subjective operationalization of Sen's concept of
      capability-and subjective well-being are increasingly regarded as relevant
      information about individual well-being to guide resources allocation in
      healthcare. Although they refer to different notions, both types of measures rely
      on self-reported information and little is known as to how they compare together
      empirically. The aim of this paper is to investigate differences between measures
      of subjective well-being and of perceived capabilities in terms of their
      correlation with dimensions of health-related quality of life using panel data
      concerning a sample of 293 breast cancer and melanoma patients. Regression
      analyses suggest that the measures capture quite different aspects of the
      patients' welfare. Differences in the correlation with dimensions of health also
      seem consistent with the underlying notions to which these measures refer.
      However, our findings also suggest that future researches should aim at
      determining how measures of perceived capabilities may be influenced by
      individual personality traits.

PMID- 29572759
TI  - Insect growth regulatory activity of carvacrol-based 1,3,4-thiadiazoles and 1,3,4
      oxadiazoles.
AB  - In designing of novel insect growth regulators (IGRs), biologically occurring
      carvacrol has been structurally modified to thiadiazole and oxadiazole moieties.
      Two series of carvacrol analogs containing 1,3,4-thiadiazole (VIIIa-e) and 1,3,4
      oxadiazole (IXa-e) derivatives are designed and synthesized. Their structures are
      confirmed by FT-IR, [Formula: see text] NMR, [Formula: see text]C NMR and LC-MS.
      IGR activity is tested against Spodoptera litura. Several analogs displayed IGR
      activity against this insect pest. Compounds VIIIe and IXe displayed relatively
      good IGR activity with [Formula: see text]values 117.43 and 108.83 ppm against
      Spodoptera litura, respectively. Synthesis, characterization and evaluation of
      carvacrol-based 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives as potent
      insect growth regulators (IGRs).

PMID- 29572760
TI  - Comparison between albino and pigmented rabbit ERGs.
AB  - BACKGROUND: Pigmented and albino rabbits are commonly used in visual research;
      however, the lack of pigment in the eyes may affect retinal responses. Here, we
      compare and describe the differences of retinal function between pigmented
      (English Butterfly) and albino (New Zealand) rabbits. METHODS: Electroretinograms
      were recorded in pigmented and albino rabbits in the dark-adapted eye, in the
      light-adapted eye and for four temporal frequencies in the light-adapted eye. The
      implicit time and amplitude of the a- and b-waves were analyzed, as well as the
      amplitude and phase of the first harmonic component of the photopic flicker
      response. RESULTS: Albino rabbits presented significantly larger amplitudes for
      both a- and b-waves at all intensities and frequencies. The intensity-response
      function of the scotopic b-wave also showed that the albino retina is more
      sensitive than the pigmented retina and the larger flicker amplitudes found in
      the albino group also revealed post-receptoral changes specifically related to
      cone pathways. CONCLUSIONS: The larger amplitude of albino receptoral and post
      receptoral activities might be attributed to greater availability of light due to
      scatter and reflection at the retinal layer, and as the differences in response
      amplitudes between the groups increase with flicker frequency, we suggest that ON
      bipolar cells recover faster in the albino group, suggesting that this might be a
      mechanism to explain the higher temporal resolution for albinos compared to the
      pigmented group.

PMID- 29572762
TI  - Association of Depressive Symptoms with Lapses in Antiretroviral Medication
      Adherence Among People Living with HIV: A Test of an Indirect Pathway.
AB  - Viral suppression, a critical component of HIV care, is more likely when
      individuals initiate antiretroviral therapy (ART) early in disease progression
      and maintain optimal levels of adherence to ART regimens. Although several
      studies have documented the negative association of depressive symptoms with ART
      adherence, less is known about how depressed mood relates to intentional versus
      unintentional lapses in adherence as well as the mechanisms underlying this
      association. The purpose of the current study was to examine the association of
      depressive symptoms with ART adherence, assessed as a multidimensional construct.
      Secondarily, this study conducted preliminary indirect path models to determine
      if medication self-efficacy could explain the depressed mood-adherence
      relationship. Depressive symptoms were not associated with 95% ART taken, self
      reported viral load, deliberate adjustments to ART regimens or skipped ART doses.
      However, the indirect association of depressive symptoms via decrements in
      medication self-efficacy was significant for 95% ART taken, self-reported viral
      load and skipped ART doses, but not deliberate changes to ART regimens. In this
      sample of HIV-positive outpatients, there is evidence to support medication self
      efficacy as a potential mechanism underlying the association between depressive
      symptoms and ART adherence. Additional longitudinal studies are needed to
      formally examine medication taking self-efficacy as a mediator.

PMID- 29572761
TI  - Efficacy of weekly administration of paclitaxel and carboplatin for advanced
      ovarian cancer patients with poor performance status.
AB  - OBJECTIVE: The aim of this study was to reveal the efficacy of weekly
      administration of paclitaxel and carboplatin for advanced ovarian cancer patients
      with poor performance status (PS). METHODS: FIGO stage III/IV ovarian cancer or
      fallopian tube cancer patients who underwent interval debulking surgery (IDS)
      followed by neoadjuvant chemotherapy (NAC) were analyzed retrospectively.
      Patients were divided into two groups based on NAC: weekly paclitaxel and
      carboplatin (W-TC) and 3 weeks of paclitaxel and carboplatin (TW-TC). Toxicity,
      efficacy of NAC, surgery outcome, and prognosis were assessed by comparing the
      two groups. RESULTS: Twenty patients treated with W-TC and 18 patients treated
      with TW-TC were analyzed. All of the W-TC patients were poor PS (PS >= 2), and
      all of the TW-TC patients were good PS (PS <= 1). The overall clinical response
      rates were 70% in W-TC and 83.4% in TW-TC. In the W-TC group, Grade 3/4 anemia
      and thrombocytopenia and greater than grade 2 neuropathy were significantly
      reduced compared to TW-TC patients. A frequency of treatment delay greater than 7
      and 14 days, G-CSF support, blood transfusion, and dose reduction or regimen
      change were also significantly reduced in the W-TC group. The rate of IDS,
      optimal debulking surgery, complications during operation, and blood transfusion
      were similar between the W-TC and TW-TC groups. Progression-free survival and
      overall survival were also similar between the two groups. CONCLUSION: Our study
      suggested that NAC with W-TC for poor PS patients with non-treated ovarian cancer
      reduced the toxicity of chemotherapy and had the same efficacy as TW-TC.

PMID- 29572763
TI  - NVVC/NHJ Durrer prizes 2017.

PMID- 29572764
TI  - Device Utilization Ratios in Infection Prevention: Process or Outcome Measure?
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the role of device
      utilization as a component of surveillance for healthcare-associated infections
      and describe its potential role as a measurement of healthcare quality. RECENT
      FINDINGS: Device utilization, while primarily a process-based measure in the
      prevention of device-associated infections can also serve as an important outcome
      in the evaluation of an infection prevention program. Device utilization can be
      an important and resource-efficient measurement when coupled with measurements of
      risk-adjusted infection rates. The measurement of the device utilization ratio
      can provide insight into the risk of device-associated harms, including non
      infectious harms, which would not be captured with currently used infection-based
      surveillance metrics. Further study and validation of standardized, risk-adjusted
      device utilization measurements is an important area for future exploration.

PMID- 29572766
TI  - CD3+ CD56+ EBER1+ atypical extraosseous plasmacytoma of the nasal cavity.
AB  - We present a case of atypical extraosseous plasmacytoma (EP) with a plasmablastic
      morphology and CD3+ CD56+ Epstein-Barr virus-encoded RNA-1 (EBER1)+ phenotypes of
      the nasal cavity. A 51-year-old male attended a local hospital with a tumor
      located in his left nasal cavity that was histologically diagnosed as extranodal
      NK/T cell lymphoma, nasal type. We reviewed the specimens and re-biopsied the
      tumor, and confirmed that the tumor was positive for CD3, CD56, and EBER1;
      however, the tumor showed a plasmablastic morphology without necrosis and
      angiocentricity, and was positive for CD138, but negative for CD20 and PAX5.
      Given a plasmablastic morphology and EBER1 positivity, but a relatively low Ki67
      index (30%), we diagnosed the case as atypical EP. The CHOP regimen was
      administered and complete remission achieved. This case indicated that EP should
      be considered as a differential diagnosis even when a tumor shows large cell
      morphology and is positive for CD3, CD56, and EBER1.

PMID- 29572765
TI  - Standardizing procedures improves and homogenizes short-term outcomes after
      minimally invasive esophagectomy.
AB  - PURPOSE: Esophageal cancer is one of the deadliest cancers worldwide.
      Esophagectomy with lymphadenectomy is regarded as the only curative option for
      resectable esophageal cancer, but it is associated with high morbidity and
      mortality. Multidisciplinary team (MDT) management was recently associated with
      improved outcomes after surgery for esophageal cancer. The aim of this study was
      to investigate the effect of standardizing procedures for minimally invasive
      esophagectomy (MIE) in the MDT setting. METHODS: This was a case-matched control
      study of 154 patients with esophageal cancer who underwent thoracoscopic
      esophagectomy in the prone position (TEP) between 2012 and 2016. Surgery was
      performed by two attending surgeons (surgeons A and B) who began working together
      in the same MDT in 2015. At that time, the following surgical procedures were
      standardized between surgeons A and B: mediastinal lymphadenectomy, abdominal
      procedures, and estimation of the blood supply of the gastric conduit. Short-term
      outcomes were compared between the following paired groups using propensity
      scores: surgeon A's pre- and post-standardization groups, surgeon B's pre- and
      post-standardization groups, and surgeon A's post-standardization group and
      surgeon B's post-standardization group. RESULTS: Concerning surgeon A, the
      estimated total blood loss in the post-standardization group (142 +/- 87 mL) was
      significantly lower than that in the pre-standardization group (376 +/- 215 mL, P
      = 0.006). The rate of left recurrent laryngeal nerve palsy in the post
      standardization group (13%) was significantly lower than that in the pre
      standardization group (47%, P = 0.046). Concerning surgeon B, the rate of
      anastomotic leakage in the post-standardization group (0%) was significantly
      lower than that in the pre-standardization group (11%, P = 0.039). Comparing the
      post-standardization groups of surgeons A and B, there were no significant
      differences in operative outcomes or morbidity. CONCLUSIONS: Standardizing
      procedures for MIE improved and homogenized surgical short-term outcomes.

PMID- 29572767
TI  - The impact of photobiomodulation on osteoblast-like cell: a review.
AB  - In this study, we present a review of the literature on the impact of
      photobiomodulation on osteoblast-like cell culture. Searches were performed in
      the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online),
      SCOPUS, and SPIE digital library databases for original articles regarding the
      effects of LLLT on osteoblast-like cells in experimental models using LLLT
      published in English from the last 20 years. The search identified 1439 studies.
      After the analysis of the abstracts, 1409 studies were excluded and 30 studies
      were then selected for the full-text analysis, 8 of which were excluded. Thus, 22
      studies were included for a critical evaluation of the impact of
      photobiomodulation on osteoblast-like cell culture. The cell lineages studied
      were primary rat, primary human, saos-2, Osteo-1, MC3T3, MG63, and OFCOL II.
      Moreover, a wide variety of experimental models were used to experimentally
      analyze the impact of photobiomodulation, the most common of which were alkaline
      phosphatase, MTT, and cell count. This review suggests that osteoblastic-like
      cells are susceptible to photobiomodulation but that most of the light parameters
      varied by different authors have little to no influence on proliferation but very
      high levels of irradiance have demonstrated deleterious effects on proliferation,
      highlighting the bi-phasic effect of photobiomodulation.

PMID- 29572769
TI  - Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy/One Anastomosis
      Duodenal Switch (SADI-S/OADS) IFSO Position Statement.
AB  - The International Federation for the Surgery of Obesity and Metabolic Disorders
      (IFSO) has played an integral role in educating both the metabolic surgical and
      the medical community at large about the role of innovative and new surgical and
      or endoscopic interventions in treating adiposity-based chronic diseases. The
      single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is also
      called the one anastomosis duodenal switch (OADS). This is a relatively new
      procedure that has been proposed as an alternative to the currently accepted
      duodenal switch (DS) procedure. The IFSO commissioned a task force (Appendix 1)
      to determine if SADI-S/OADS is an effective and safe procedure and if it should
      be considered a surgical option for the treatment of adiposity and adiposity
      based chronic diseases. The following position statement is issued by the IFSO
      SADI-S/OADS task force and approved by the IFSO Executive Board. This statement
      is based on current clinical knowledge, expert opinion and published peer
      reviewed scientific evidence. It will be reviewed in 2 years.

PMID- 29572770
TI  - Compulsive Sexual Behavior as an Impulse Control Disorder: Awaiting Field Studies
      Data.

PMID- 29572768
TI  - Candidemia in Adults at a Tertiary Hospital in China: Clinical Characteristics,
      Species Distribution, Resistance, and Outcomes.
AB  - BACKGROUND: Candidemia is one of the most common nosocomial bloodstream
      infections. Early diagnosis and antifungal treatment improve clinical outcomes in
      some studies but not all, with diverse data reported from different institutions.
      Similarly, antifungal resistance is more common in the USA than in Europe, but
      there is little data regarding the microbiology and clinical course of candidemia
      in adult patients in Asia. AIMS: (1) To capture species distribution and drug
      resistance rates among Candida bloodstream isolates, (2) to describe clinical
      features of candidemia, and (3) to identify factors associated with all-cause
      mortality, with emphasis on early initiation of antifungal treatment, at a large
      tertiary University Hospital in China. METHODS: In this single-center
      retrospective study, we identified all patients with candidemia, between 2008 and
      2014. Demographic and clinical characteristics, microbiological information,
      details of antifungal therapy and clinical outcomes were collected. RESULTS: We
      studied 166 patients. 71 (42.8%) had cancer. Candida albicans was the most
      frequent species (37.3%), followed by C. parapsilosis (24.1%), C. tropicalis
      (22.8%), and C. glabrata (14.5%). Antifungal resistance was more frequent in non
      albicans strains and especially C. glabrata. Twenty patients received
      inappropriate treatment with all-cause mortality of 35%. The remaining 146
      patients had significantly lower mortality (21.9%, P = 0.045). Among patients who
      received antifungal treatment, mortality rate increased with time to appropriate
      antifungal therapy (AAT): 13.7%, for < 24 h, 21.1% for 24-48 h, 23.1% for > 48 h,
      and 32.4% among patients who received no AT (chi2 for trend P = 0.039).
      Initiating AAT more than 24 h after blood culture collection was an independent
      risk factor for mortality, after adjustment for other confounders (OR 7.1, 95% CI
      1.3-39.4, P = 0.024). CONCLUSIONS: Candida albicans was the most frequent cause
      of candidemia at a large tertiary hospital in China, but antifungal resistance is
      a growing concern among non-albicans Candida species. The mortality rate of
      patients treated with ineffective antifungal agents based on in vitro
      susceptibilities was similar to that of patients who received no treatment at
      all, and delayed initiation of antifungal treatment was associated with increased
      risk of death.

PMID- 29572772
TI  - Hydroxyhydroquinone impairs fat utilization in mice by reducing nitric oxide
      availability.
AB  - Habitual consumption of chlorogenic acid compounds (CGAs) from coffee increases
      fat catabolism and reduces body fat; however, the contribution of roasted coffee
      remains unclear. Hydroxyhydroquinone (HHQ) impairs the vasodilatory and
      antihypertensive effects of CGAs by reducing nitric oxide (NO) bioavailability.
      Since HHQ also reduces fat catabolism, we hypothesized that HHQ does so by
      decreasing NO availability. Therefore, we investigated the effect of HHQ on
      energy metabolism in KKAy mice. In HHQ-treated mice, fat oxidation was
      significantly low and dose-dependent, serum and urinary hydrogen peroxide were
      high, and plasma NO metabolites and S-nitrosylated liver proteins were low. In
      HHQ-treated mouse hepatocytes, the palmitate-induced increase in cellular oxygen
      consumption was negatively affected, and HHQ or L-NAME reduced cellular fatty
      acid utilization. In conclusion, HHQ can impair fat utilization by reducing NO
      availability in mice. Protein S-nitrosylation reduction in liver cells after HHQ
      consumption may be associated with impaired fatty acid oxidation.

PMID- 29572771
TI  - Brain functional connectivity correlates of coping styles.
AB  - Coping abilities represent the individual set of mental and behavioral strategies
      adopted when facing stress or traumatic experiences. Coping styles related to
      avoidance have been linked to a disposition to develop psychiatric disorders such
      as PTSD, anxiety, and major depression, whereas problem-oriented coping skills
      have been positively correlated with well-being and high quality of life. Even
      though coping styles constitute an important determinant of resilience and can
      impact many aspects of everyday living, no study has investigated their brain
      functional connectivity underpinnings in humans. Here we analyzed both
      psychometric scores of coping and resting-state fMRI data from 102 healthy adult
      participants. Controlling for personality and problem-solving abilities, we
      identified significant links between the propensity to adopt different coping
      styles and the functional connectivity profiles of regions belonging to the
      default mode (DMN) and anterior salience (AS) networks-namely, the anterior
      cingulate cortex, left frontopolar cortex, and left angular gyrus. Also, a
      reduced negative correlation between AS and DMN nodes explained variability in
      one specific coping style, related to avoiding problems while focusing on the
      emotional component of the stressor at hand, instead of relying on cognitive
      resources. These results might be integrated with current neurophysiological
      models of resilience and individual responses to stress, in order to understand
      the propensity to develop clinical conditions (e.g., PTSD) and predict the
      outcomes of psychotherapeutic interventions.

PMID- 29572773
TI  - Traditions, Paradigms and Basic Concepts in Islamic Psychology.
AB  - The conceptual tools of psychology aim to explain the complexity of phenomena
      that psychotherapists observe in their patients and within themselves, as well as
      to predict the outcome of therapy. Naturally, Muslim psychologists have sought
      satisfaction in the conceptual tools of their trade and in what has been written
      in Islamic psychology-notably by Badri (The dilemma of Muslim psychologists, MWH
      London, London, 1979), who critiqued Western psychology from an Islamic
      perspective, arguing the need to filter out from Western Psychology which was
      cross-culturally invalid or was in conflict with Islamic precept. In this paper,
      I advocate an extension of Badri's (1979) approach and present a working model of
      the self derived from traditional Islamic thought. This model, though rudimentary
      and incomplete, I believe, makes better sense of my perceptions as a clinician
      than any other psychological model within my knowledge.

PMID- 29572774
TI  - Identification, Characterization, and Mapping of a Novel SNP Associated with Body
      Color Transparency in Juvenile Red Sea Bream (Pagrus major).
AB  - We previously reported a body color deformity in juvenile red sea bream, which
      shows transparency in the juvenile stage because of delayed chromatophore
      development compared with normal individuals, and this finding suggested a
      genetic cause based on parentage assessments. To conduct marker-assisted
      selection to eliminate broodstock inheriting the causative gene, developing DNA
      markers associated with the phenotype was needed. We first conducted SNP mining
      based on AFLP analysis using bulked-DNA from normal and transparent individuals.
      One SNP was identified from a transparent-specific AFLP fragment, which
      significantly associated with transparent individuals. Two alleles (A/G) were
      observed in this locus, and the genotype G/G was dominantly observed in the
      transparent groups (97.1%) collected from several production lots produced from
      different broodstock populations. A few normal individuals inherited the G/G
      genotype (5.0%), but the A/A and A/G genotypes were dominantly observed in the
      normal groups. The homologs region of the SNP was searched using a medaka genome
      database, and intron 12 of the Nell2a gene (located on chromosome 6 of the medaka
      genome) was highly matched. We also mapped the red sea bream Nell2a gene on the
      previously developed linkage maps, and this gene was mapped on a male linkage
      group, LG4-M. The newly found SNP was useful in eliminating broodstock possessing
      the causative gene of the body color transparency observed in juvenile stage of
      red sea bream.

PMID- 29572775
TI  - Development and Application of Liquid Biopsies in Metastatic Prostate Cancer.
AB  - PURPOSE OF REVIEW: Metastatic prostate cancer is a lethal and highly
      heterogeneous malignancy, associated with a broad spectrum of potentially
      actionable molecular alterations. In the past decade, disease profiling has
      expanded to include not only traditional tumor tissue, but also liquid biopsies
      of cells and genetic material circulating in the blood. These liquid biopsies
      offer a minimally invasive, repeatable source of tumor material for longitudinal
      disease profiling but also raise new technical and biological challenges. Here we
      will summarize recent advances in liquid biopsy strategies and the role they have
      played in biomarker development and disease management. RECENT FINDINGS:
      Technologies for analysis of circulating tumor cells (CTCs) continue to evolve
      rapidly, and the latest high content scanning platforms have underscored the
      phenotypic heterogeneity of CTC populations. Among liquid biopsies, CTC
      enumeration remains the most extensively validated prognostic marker to date, but
      other clinically relevant phenotypes like androgen receptor (AR) localization or
      presence of AR-V7 splice variant are important new predictors of therapy
      response. Serial genomic profiling of CTCs or circulating tumor DNA (ctDNA) is
      helping to define primary and acquired resistance mechanisms and helping to guide
      patient selection for targeted therapies such as poly(adenosine diphosphate [ADP]
      ribose) polymerase (PARP) inhibition. The era of liquid biopsy-based biomarkers
      has arrived, driven by powerful new enrichment and analysis techniques. As new
      blood-based markers are identified, their biological significance as disease
      drivers must be elucidated to advance new therapeutic strategies, and their
      clinical impact must be translated through assay standardization, followed by
      analytical and clinical validation. These efforts, already ongoing on multiple
      fronts, constitute the critical steps toward more effective precision management
      of advanced prostate cancer.

PMID- 29572776
TI  - Exome sequencing confirms molecular diagnoses in 38 Chinese families with
      hereditary spherocytosis.
AB  - Hereditary spherocytosis (HS), the most common cause of congenital hemolytic
      anemia, is caused by deficiency of the erythrocyte membrane proteins. Five
      causative genes (ANK1, SPTB, SPTA1, SLC4A1, and EPB42) have been identified. To
      date, molecular genetic studies have been performed in different populations,
      including the American, European, Brazilian, Japanese and Korean populations,
      whereas only a few studies have been described in the Chinese population. Here,
      by reanalysis of the exome data, we revealed causative mutations and established
      a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel
      mutations and four reported mutations in three known HS-causing genes-17 in ANK1,
      17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes
      in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered
      throughout the entire genes, are non-recurrent; and most of them are null
      mutations, which might cause HS via a haploinsufficiency mechanism. De novo
      mutations in ANK1 or SPTB often occur with an unexpected high frequency (87.5%
      and 64.2%, respectively). Our study updates our knowledge about the genetic
      profile of HS in Chinese and shows that family-based, especially parent-offspring
      trio, sequencing analysis can help to increase the diagnostic power and improve
      diagnostic efficiency.

PMID- 29572777
TI  - Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient
      breast cancer therapy.
AB  - Paclitaxel (PTX) is one of the most effective anticancer drugs for the treatment
      of various solid tumors, but its clinical use is limited by its poor solubility,
      low bioavailability, and severe systemic toxicity. Encapsulation of PTX in
      polymeric nanoparticles is used to overcome these problems but these micelles
      still need improvements in stability, pharmacokinetics, therapeutic efficacy, and
      safety profiles. In this study, we demonstrate a facile fabrication of a stable
      PTX-binding micelle made from poly (ethylene glycol)-block-dendritic polylysine,
      whose primary amines were reacted with phenethyl isothiocyanate (PEITC), a
      hydrophobic anticancer agent under clinical study. The amphiphilic conjugate (PEG
      Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined
      micelles whose core was composed of phenyl groups and thiourea groups binding PTX
      via pi-pi stacking and hydrogen bonding. Compared with the PTX-loaded
      poly(ethylene glycol)-block-poly(D,L-lactide) (PEGPDLLA/ PTX) micelles in
      clinical use, PTX-loaded PEG-Gx-PEITC third-generation (PEG-G3-PEITC/PTX)
      micelles showed slowed blood clearance, enhanced tumor accumulation, and thus
      much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic
      human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug
      delivery system for PTX in the treatment of breast cancer.

PMID- 29572778
TI  - The Intersection of Emotional and Sociocognitive Competencies with Civic
      Engagement in Middle Childhood and Adolescence.
AB  - Civic developmental theory anticipates connections between normative
      developmental competencies and civic engagement, but little previous research has
      directly studied such links. The current study sought to contribute to civic
      development theory by examining associations between emotional and sociocognitive
      competencies (empathy, emotion regulation, prosocial moral reasoning, future
      orientation) and civic engagement (volunteering, informal helping, political
      behaviors and beliefs, environmental behaviors, social responsibility values,
      civic skills). Data came from a geographically and racially diverse sample of
      2467 youth (Mage = 13.4, Range: 8-20 years, 56% female). The results indicated
      that empathy and future-orientation significantly predicted nearly all forms of
      civic engagement, whereas emotion regulation and prosocial moral reasoning were
      uniquely associated with specific forms of civic engagement. Exploratory multi
      group models indicated that empathy and emotion regulation were more strongly
      associated with civic engagement among younger youth and prosocial moral
      reasoning and future-orientation were more strongly related to civic engagement
      among older youth. The findings help to advance developmental theory of youth
      civic engagement.

PMID- 29572779
TI  - How Social and Mass Media Relate to Youth's Self-Sexualization: Taking a Cross
      National Perspective on Rewarded Appearance Ideals.
AB  - Although media exposure has been related to cognitive preoccupation with
      appearance, research rarely investigated adolescents' behavioral self
      sexualization. To address this gap, the present study among 12- to 16-year-olds
      (N = 1527; 50.2% girls) in Austria, Belgium, Spain, and South-Korea (1)
      investigates whether different types of media use relate to self-sexualization,
      (2) explores the explanatory value of rewarded appearance ideals, and (3)
      considers culture and gender as moderating factors. Despite cultural variation, a
      general trend of increasing self-sexualization with social media use and magazine
      reading appeared across the countries. Moreover, women's magazine reading and
      rewards were related to self-sexualization among all the girls across the
      countries, which suggests that girls may be more vulnerable to the examined
      effects. Overall, this study provides a better understanding of the unique
      contribution of specific media genres to youth's self-sexualization and points at
      the importance of social media use in girls' and boys' engagement in sexualizing
      appearance behaviors across four countries.

PMID- 29572780
TI  - Mathematical modeling of cancer-immune system, considering the role of
      antibodies.
AB  - A mathematical model for the quantitative analysis of cancer-immune interaction,
      considering the role of antibodies has been proposed in this paper. The model is
      based on the clinical evidence, which states that antibodies can directly kill
      cancerous cells (Ivano et al. in J Clin Investig 119(8):2143-2159, 2009). The
      existence of transcritical bifurcation, which has been proved using Sotomayor
      theorem, provides strong biological implications. Through numerical simulations,
      it has been illustrated that under certain therapy (like monoclonal antibody
      therapy), which is capable of altering the parameters of the system, cancer-free
      state can be obtained.

PMID- 29572782
TI  - A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with
      locally advanced non-small cell lung cancer.
AB  - Background Radiotherapy (RT) is an effective treatment for elderly patients with
      locally advanced non-small-cell lung cancer (NSCLC); however, no clinical trials
      have investigated combination RT with pemetrexed (PEM) in chemotherapy-naive
      patients >=71 years old. We conducted a phase I/II study to evaluate the
      appropriate PEM dose, efficacy, and safety of PEM plus RT in elderly patients.
      Methods Patients >=71 years with performance status (PS) scores of 0-2 who had
      pathologically confirmed stage IIIA/IIIB NSCLC received PEM (500 mg/m2 on day 1
      of a 28-day cycle, 4 courses) and RT (a single 2 Gy daily fraction on 5
      consecutive days weekly from day 1; 60 Gy total). The primary endpoint was the
      objective response rate (ORR); the secondary endpoints were progression-free
      survival (PFS), overall survival (OS), and adverse events (AEs). Results Forty
      one patients with a median age of 79 years were enrolled; 31 were men. Eighteen
      patients had squamous cell carcinoma, 27 had stage IIIA disease, and 38 had PS
      scores 0-1. The ORR was 80.5%, while the median OS and PFS rates were 24.9 and
      6.9 months, respectively. Two treatment-related deaths occurred owing to RT
      related pneumonitis and severe infection, respectively. Common hematological AEs
      were leucopenia and neutropenia; common non-hematological AEs were anorexia and
      constipation. Three patients developed PEM-induced interstitial lung disease;
      however, most AEs were RT-related. Conclusions Combination PEM and RT shows
      promising efficacy but relatively severe RT-related toxicities. Therefore, this
      treatment should be prescribed to elderly patients with caution. Trial
      registration UMIN 000005036 .

PMID- 29572784
TI  - Chemical shift assignments of RHE_RS02845, a NTF2-like domain-containing protein
      from Rhizobium etli.
AB  - The nuclear transport factor 2 (NTF2) like superfamily includes members of the
      NTF2 family, delta-5-3-ketosteroid isomerases, and the beta subunit of ring
      hydroxygenases. This family plays important roles in both eukaryotic and
      prokaryotic cells, and is taken as a classic example of divergent evolution
      because proteins in this family exhibit diverse biological functions, although
      share common structural features. We cloned the gene RHE_RS02845 encoding a
      predicted NTF2-like domain-containing protein in Rhizobium etli, and prepared U
      13C/15N-labeled protein samples for its three-dimensional NMR structural
      determination. Here, chemical shift assignments for both backbone and side-chain
      atoms are reported, which is prerequisite for further structural calculation and
      functional research using NMR spectroscopy.

PMID- 29572783
TI  - Post-progression survival following second-line chemotherapy in patients with
      advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis.
AB  - Background Post-progression survival (PPS) could be a confounding element in
      interpreting data from clinical trials of second-line chemotherapy in patients
      with advanced pancreatic cancer (PC) previously treated with gemcitabine (GEM)
      because a recent meta-analysis of oxaliplatin combination therapy showed
      statistical heterogeneity for overall survival (OS) but not for progression-free
      survival (PFS). This study aimed to improve the understanding of the impact of
      PPS on OS in this setting. Methods Databases were searched to identify randomized
      controlled trials (RCTs) in the salvage setting. We evaluated relationships
      between OS and PFS, PPS, and other variables. Results Totally, 17 RCTs with 3253
      patients were identified. Median OS was strongly and moderately associated with
      median PPS and PFS, respectively (r = 0.913; p < 0.001 and 0.780; p < 0.001,
      respectively). The proportion of patients with good performance status was
      significantly associated with both PPS and PFS (r = 0.574, p < 0.001 and 0.492, p
      < 0.001, respectively). The induction rate of subsequent chemotherapy was related
      to the duration of PPS and OS (r = 0.640, p < 0.001 and 0.647, p < 0.001,
      respectively). Median PPS and OS were significantly longer in recent trials than
      those in older trials (3.55 versus 2.78 months, p < 0.001 and 6.29 versus 5.02
      months, p < 0.001). Conclusions Median PPS was strongly correlated with median
      OS. Given the recently increased opportunity for subsequent chemotherapy and
      supportive care, PPS may serve as an important element to clarify problems in
      this setting.

PMID- 29572785
TI  - Partial solid-state NMR 1H, 13C, 15N resonance assignments of a perdeuterated
      back-exchanged seven-transmembrane helical protein Anabaena Sensory Rhodopsin.
AB  - Anabaena Sensory Rhodopsin (ASR) is a unique photochromic membrane-embedded
      photosensor which interacts with soluble transducer and is likely involved in a
      light-dependent gene regulation in the cyanobacterium Anabaena sp. PCC 7120. We
      report partial spectroscopic 1H, 13C and 15N assignments of perdeuterated and
      back-exchanged ASR reconstituted in lipids. The reported assignments are in
      general agreement with previously determined assignments of carbon and nitrogen
      resonances in fully protonated samples. Because the back-exchange was performed
      on ASR in a detergent-solubilized state, the location of detected residues
      reports on the solvent accessibility of ASR in detergent. A comparison with the
      results of previously published hydrogen/exchange data collected on the ASR
      reconstituted in lipids, suggests that the protein has larger solvent accessible
      surface in the detergent-solubilized state.

PMID- 29572781
TI  - Noradrenergic Modulation on Dopaminergic Neurons.
AB  - It is now well accepted that there is a close relationship between noradrenergic
      and dopaminergic neurons in the brain, especially referring to the modulation of
      the locus coeruleus-norepinephrine (LC-NE) system on dopamine transmission. The
      disturbance of this modulation may contribute to neurodegeneration of
      dopaminergic neurons in Parkinson's disease. In this article, we briefly review
      evidence related to such modulation. Firstly, we illustrated the noradrenergic
      innervation and functional implication for the LC-NE system and nigra-striatum
      dopaminergic system. Furthermore, we depicted neuroprotective effects of the LC
      NE on dopaminergic neurons in vivo and in vitro. Moreover, we present data
      implicating the potential mechanisms underlying the modulation of the LC-NE
      system on dopaminergic neurons, in particular the effects of NE as a neurotrophic
      factor and through its ability to stimulate the expression of other neurotrophic
      factors, such as the brain-derived neurotrophic factor. Finally, we discussed
      other mechanisms intrinsic to NE's effects. A better understanding of the
      noradrenergic modulation on dopaminergic neurons may be rewarding by significant
      advances in etiologic study and promising treatment of Parkinson's disease.

PMID- 29572787
TI  - Reasoning from an incompatibility: False dilemma fallacies and content effects.
AB  - In the present studies, we investigated inferences from an incompatibility
      statement. Starting with two propositions that cannot be true at the same time,
      these inferences consist of deducing the falsity of one from the truth of the
      other or deducing the truth of one from the falsity of the other. Inferences of
      this latter form are relevant to human reasoning since they are the formal
      equivalent of a discourse manipulation called the false dilemma fallacy, often
      used in politics and advertising in order to force a choice between two selected
      options. Based on research on content-related variability in conditional
      reasoning, we predicted that content would have an impact on how reasoners treat
      incompatibility inferences. Like conditional inferences, they present two invalid
      forms for which the logical response is one of uncertainty. We predicted that
      participants would endorse a smaller proportion of the invalid incompatibility
      inferences when more counterexamples are available. In Study 1, we found the
      predicted pattern using causal premises translated into incompatibility
      statements with many and few counterexamples. In Study 2A, we replicated the
      content effects found in Study 1, but with premises for which the incompatibility
      statement is a non-causal relation between classes. These results suggest that
      the tendency to fall into the false dilemma fallacy is modulated by the
      background knowledge of the reasoner. They also provide additional evidence on
      the link between semantic information retrieval and deduction.

PMID- 29572786
TI  - Changes in hemoglobin profile reflect autologous blood transfusion misuse in
      sports.
AB  - The changes in hemoglobin (Hb) profile following autologous blood transfusion
      (ABT) for the first time were studied for anti-doping purposes. Twenty-four
      healthy, trained male subjects (aged 18-40) were enrolled and randomized into
      either the transfusion (T) or control (C) groups. Blood samples were taken from
      the T subjects at baseline, after withdrawal and reinfusion of 450 ml of
      refrigerated or cryopreserved blood, and from C subjects at the same time points.
      Hematological variables (Complete blood count, Reticulocytes, Immature
      Reticulocytes Fraction, Red-cell Distribution Width, OFF-hr score) were measured.
      The Hb types were analyzed by high-performance liquid chromatography and the
      Hemoglobin Profile Index (HbPI) arbitrarily calculated. Between-group differences
      were observed for red blood cells and reticulocytes. Unlike C, the T group, after
      withdrawal and reinfusion, showed a significant trend analysis for both
      hematological variables (Hemoglobin concentration, reticulocytes, OFF-hr score)
      and Hb types (glycated hemoglobin-HbA1c, HbPI). The control charts highlighted
      samples with abnormal values (> 3-SD above/below the population mean) after
      reinfusion for hematological variables in one subject versus five subjects for
      HbA1c and HbPI. A significant ROC-curve analysis (area = 0.649, p = 0.015)
      identified a HbA1c cut-off value <= 2.7% associated to 100% specificity of blood
      reinfusion (sensitivity 25%). Hemoglobin profile changed in trained subjects
      after ABT, with abnormal values of HbA1c and HbPI in 42% of subjects after
      reinfusion. Future studies will confirm the usefulness of these biomarkers in the
      anti-doping field.

PMID- 29572789
TI  - 3D Sponge-Matrix Histoculture: An Overview.
AB  - Three-dimensional cell culture and tissue culture (histoculture) is much more in
      vivo-like than 2D culture on plastic. Three-dimensional culture allows
      investigation of crucial events in tumor biology such as drug response,
      proliferation and cell cycle progression, cancer cell migration, invasion,
      metastasis, immune response, and antigen expression that mimic in vivo
      conditions. Three-dimensional sponge-matrix histoculture maintains the in vivo
      phenotype, including the formation of differentiated structures of normal and
      malignant tissues, perhaps due to cells maintaining their natural shape in a
      sponge-gel matrix such as Gelfoam(r). Sponge-matrix histoculture can also support
      normal tissues and their function including antibody-producing lymphoid tissue
      that allows efficient HIV infection, hair-growing skin, excised hair follicles
      that grow hair, pluripotent stem cells that form nerves, and much more.

PMID- 29572790
TI  - In Vivo-Like Growth Patterns of Multiple Types of Tumors in Gelfoam(r)
      Histoculture.
AB  - Diverse human tumors obtained directly from surgery or biopsy can grow at high
      frequency in 3-dimensional Gelfoam(r) histoculture for long periods of time and
      still maintain many of their in vivo properties. The in vivo properties
      maintained in vitro include 3-dimensional growth; maintenance of tissue
      organization and structure, such as changes associated with oncogenic
      transformation; retention of differentiated function; tumorigenicity; and growth
      of multiple types of cells from a single tumor.

PMID- 29572791
TI  - Expression and Targeting of Tumor Markers in Gelfoam(r) Histoculture: Potential
      Individualized Assays for Immuno-Oncology.
AB  - Tumor-specific antigens are important in the study of tumor biology, tumor
      diagnosis, and prognosis and as targets for tumor therapy. This chapter reviews
      patient colon, breast, and ovarian tumors in 3-dimensional Gelfoam(r)
      histoculture maintaining in vivo-like expression of the important tumor antigens,
      for example TAG-72 and CEA. We have also reviewed that fluorescent antibodies can
      target tumors in Gelfoam(r) histoculture, thereby providing an assay for
      individual patients for sensitivity to therapeutic antibodies which have become
      so important in immuno-oncology and other cancer therapies.

PMID- 29572792
TI  - Development of the Histoculture Drug Response Assay (HDRA).
AB  - The histoculture drug response assay (HDRA) was developed using Gelfoam(r)
      histoculture of all tumor types. Twenty tumor classes, including all the major
      ones, have been histocultured on Gelfoam(r) and tested for drug response.
      Quantitative and qualitative results show increasing cell kill with rising
      cytotoxic drug concentration, differential drug sensitivities of multiple cell
      types within individual cultured tumors, differential sensitivities to a single
      drug of a series of tumors of the same histopathological classification,
      differential sensitivities of individual tumors to a series of drugs, and
      sensitivity patterns of various tumor types similar to the sensitivities found in
      vivo. Therefore, the results indicated that precise therapeutic data can be
      obtained from tumor specimens growing in Gelfoam(r) histoculture in vitro for the
      individual cancer patient as well as for rational and relevant screening for
      novel agents active against human solid tumors.

PMID- 29572793
TI  - Diagnosis and Pathological Analysis of Patient Cancers by Detection of
      Proliferating Cells in Gelfoam(r) Histoculture.
AB  - Patient tumors grew in Gelfoam(r) histoculture with maintenance of tissue
      architecture, tumor-stromal interaction, and differentiated functions. In this
      chapter, we review the use of Gelfoam(r) histoculture to demonstrate
      proliferation indices of major solid cancer types explanted directly from
      surgery. Cell proliferation was visualized by histological autoradiography within
      the cultured tissues after [3H]thymidine incorporation by the proliferating
      cells. Epilumination polarization microscopy enables high-resolution imaging of
      the autoradiography of each cell. The histological status of the cultured tissues
      can be assessed simultaneously with the proliferation status. Carcinomas were
      observed to have areas of high epithelial proliferation with quiescent stromal
      cells. Sarcomas have high proliferation of the cancer cells of mesenchymal organ.
      Normal tissues can also proliferate at high rates. Mean growth fraction index
      (GFI) was highest for patient tumors with the pure subtype of small-cell lung
      cancer than other types of lung cancer.

PMID- 29572794
TI  - Clinical Correlation of the Histoculture Drug Response Assay in Gastrointestinal
      Cancer.
AB  - The histoculture drug response assay (HDRA) with tumors histocultured on
      Gelfoam(r) was tested for clinical correlation for advanced gastric and
      colorectal cancer patients. In one study, 29 patients were treated with drugs
      shown to be ineffective in the HDRA, and all 29 cases showed clinical
      chemoresistance. In nine patients treated with drugs shown to be effective in the
      HDRA, six showed clinical chemoresponse and three showed arrest of disease
      progression. In a study of 32 patients with stage III and IV gastric cancer
      treated with mitomycin C and 5-fluorouracil (5-FU), the survival rate of 10
      patients whose tumors were sensitive to either mitomycin C and/or 5-fluorouracil
      in the HDRA was significantly better than that of 22 patients whose tumors were
      insensitive to both drugs in the HDRA. Twenty-nine patients with stage III and IV
      colorectal cancer without remaining measurable tumor lesions after surgery were
      treated with fluoropyrimidines adjuvantly. The recurrence-free survival rate of 7
      patients whose tumors were sensitive to 5-fluorouracil in the HDRA was
      significantly better than that of 22 patients whose tumors were insensitive in
      the HDRA. In a companion study of 128 gastric cancer patients whose tumors were
      evaluated in the HDRA, the overall and disease-free survival rates of the HDRA
      sensitive group were found to be significantly higher than those of the HDRA
      resistant group, treated with the same drugs.

PMID- 29572795
TI  - Prospective Clinical Correlation of the Histoculture Drug Response Assay for
      Ovarian Cancer.
AB  - The histoculture drug response assay (HDRA) has been correlated clinically to a
      number of cancer types (please see Chaps. 7 - 11 of the present volume). The
      present chapter reviews the clinical trials of the HDRA for ovarian cancer. A
      prospective clinical trial of the HDRA for advanced epithelial ovarian cancer
      (AEOC) was performed at Asan Medical Center, Seoul, Korea. The clinical trial
      compared the efficacy of first-line therapy paclitaxel and carboplatinum in the
      HDRA and the clinical response for the patients whose tumors were tested in the
      HDRA. A series of patients (104) were treated with adjuvant combination
      chemotherapy of paclitaxel and carboplatinum after primary cytoreductive surgery.
      Tumor fragments were cultured on Gelfoam(r) and tested with paclitaxel and
      carboplatinum and evaluated with the MTT endpoint. Patients were categorized into
      two groups as either sensitive to both drugs (SS) or not sensitive to one or both
      drugs (R) based on HDRA results. The recurrence rate was much lower in the SS
      group compared to the R group, 29.2% vs. 69.8%, respectively. The SS group had a
      significantly longer progression-free survival compared to the R group, 34.0
      months vs. 16.0 months, respectively. In another clinical trial, the HDRA was
      performed on 85 cases of ovarian cancer and 97% were evaluable. HDRA results were
      correlated to clinical response of 15 patients who received cisplatinum-based
      therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true
      positive rate was 88%, the true-negative rate was 86%, the sensitivity was 88%,
      the specificity was 86%, and the accurate prediction rate was 87% when HDRA
      results were compared to the response of the treated patients.

PMID- 29572796
TI  - Clinical Correlation of the Histoculture Drug Response Assay for Head and Neck
      Cancer.
AB  - Gelfoam(r) histoculture was utilized to develop the histoculture drug response
      assay (HDRA) for head and neck cancer. Specimens of head and neck tumors were
      evaluated for sensitivity to the following drugs: cisplatinum (CDDP), 5
      fluorouracil (5-FU), and the combination of CDDP and 5-FU. In the first clinical
      study at UCSD, 10 of 12 patients with tumors that were drug sensitive in
      Gelfoam(r) histoculture had either complete or partial response clinically.
      Comparisons of HDRA results, obtained with [3H]thymidine incorporation as the
      endpoint were made with clinical responses, i.e., complete response, partial
      response, or no response. The overall accuracy of the HDRA was 74% in this
      correlative clinical trial; the predictive positive value was 83%, the
      sensitivity was 71%, and the specificity was 78%. Seven of 11 patients with HDRA
      resistant tumors demonstrated no response for a predictive negative value of 64%.
      In a subsequent study at Memorial Sloan Kettering Cancer Center, tumor specimens
      from 41 to 42 patients undergoing treatment for head and neck cancer were
      successfully evaluated by the HDRA. The histocultured tumors were treated with 5
      FU and/or CDDP and a control group received no drug treatment. After completion
      of drug treatment, the relative cell survival in the tumors was determined using
      the MTT endpoint. Sensitivity was defined as a tumor inhibition rate (IR) of
      greater than 30%. Survival comparisons were performed using the generalized
      Wilcoxon test for the comparison of Kaplan-Meier survival curves. Resistance to 5
      FU was observed in 13 cases (32%), to CDDP in 13 cases (32%), and to both agents
      in 11 cases (27%). The 2-year cause-specific survival was significantly greater
      for patients sensitive to 5-FU than patients who were resistant (85% vs. 64%),
      CDDP (86% vs. 64%), or both agents (85% vs. 63%). These results demonstrate the
      clinical usefulness of the HDRA for head and neck cancer.

PMID- 29572797
TI  - Clinical Usefulness of the Histoculture Drug Response Assay for Breast Cancer.
AB  - The histoculture drug response assay (HDRA) was used to compare drug sensitivity
      of recurrent and primary breast cancer in vitro as well as in the clinic. The
      HDRA utilizes 3-dimensional culture of human tumors on Gelfoam(r). The evaluation
      rate was 98.8%. The HDRA mean inhibition rate of primary tumors vs. recurrent
      tumors was, respectively, 57.9% and 38.6% for doxorubicin (DOX); 59.9% and 42.8%
      for mitomycin C (MMC); 49.0% and 33.4% for 5-fluorouracil (5-FU); and 34.5% and
      16.0% for cisplatinum (CDDP). The recurrent cases were pretreated clinically with
      CAF (cyclophosphamide [CTX], DOX, and 5-FU), CEF (CTX, epirubicin [EPN], and 5
      FU), or CMF (CTX, methotrexate [MTX], and 5-FU). 64.7% of the recurrent cases
      were resistant to all four agents tested compared to 27% of the primary cases.
      Only 5.9% of the recurrent cases were sensitive to three or more agents as
      opposed to 18% of the primary cases. The correlation of the HDRA results to
      clinical outcome in another breast-cancer study was 80.0% with 15 cases evaluated
      consisting of five true positives, three false positives, seven true negatives,
      and no false negatives. HDRA was also performed on surgical specimens of primary
      tumor and axillary lymph node metastasis from each of 30 breast cancer patients.
      The lymph-node metastases were more resistant than the primary tumor for DOX, 5
      FU, and MMC, but not for CDDP. The data suggest that both primary tumor and
      metastases from individual patients should be tested in the HDRA to enhance
      clinical efficacy of chemotherapy. There also was a lack of correlation with
      breast cancer subtype and drug response in the HDRA, further suggesting the
      importance of individualized treatment for breast cancer patients afforded by the
      HDRA.

PMID- 29572798
TI  - Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer
      and Benign Prostate Hypertrophy (BPH).
AB  - The histoculture drug response assay (HDRA) has been adapted to determine
      androgen sensitivity in Gelfoam histoculture of human benign prostatic tissue as
      well as prostate cancer. Gelfoam histoculture was used to measure androgen
      independent and androgen-dependent growth of benign and malignant prostate
      tissue. The androgen-sensitivity index was significantly higher in 23 paired
      specimens of prostate cancer compared to benign prostate hypertrophy (BPH).
      Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in
      Gelfoam(r) histoculture in a dose-dependent manner.

PMID- 29572799
TI  - In Vivo-Like Cell-Cycle Phase Distribution of Cancer Cells in Gelfoam(r)
      Histoculture Observed in Real Time by FUCCI Imaging.
AB  - FUCCI color codes cells as they express different color fluorescent proteins as
      they go through phases of the cell cycle. The cell cycle phase distribution of
      cancer cells in Gelfoam(r) histoculture was similar to in vivo tumors, whereby
      only the surface cells proliferate and interior cells are quiescent in G0/G1. In
      contrast, in 2D cancer-cell culture, most of the cells are always cycling. The
      cancer cells responded similarly to toxic chemotherapy in Gelfoam(r) culture as
      in vivo; as such, therapy is cell cycle dependent. In 2D culture, cancer cells
      were much more chemosensitive. These results indicate why the drug response
      pattern of tumors in Gelfoam(r) histoculture reflects what is observed in vivo.

PMID- 29572800
TI  - Methionine Dependency Determination of Human Patient Tumors in Gelfoam(r)
      Histoculture.
AB  - The elevated requirement of methionine by cancer cells (methionine dependence) is
      a general metabolic abnormality in cancer. Methionine-dependent cancer cells are
      unable to proliferate and arrest in the late S/G2 phase of the cell cycle when
      methionine is restricted in vitro or in vivo. Cell-cycle arrest in late S/G2 was
      used as a biomarker of methionine dependence for patient tumors in Gelfoam(r)
      histoculture. Human cancer patient tumors, including tumors of the colon, breast,
      ovary, prostate, and a melanoma, were observed to be methionine dependent in
      Gelfoam(r) histoculture based on cell cycle analysis. This simple method can be
      used to screen patient tumors for methionine dependence and then subsequently
      apply appropriate chemotherapy for these patients to target this cancer-specific
      metabolic abnormality.

PMID- 29572801
TI  - Hair-Shaft Growth in Gelfoam(r) Histoculture of Skin and Isolated Hair Follicles.
AB  - Human scalp skin with abundant hair follicles in various stages of the hair
      growth cycle was histocultured for up to 40 days on Gelfoam(r) at the air/liquid
      interface. The anagen hair follicles within the histoculture scalp skin produced
      growing hair shafts. Hair follicles could continue their cycle in histoculture;
      for example, apparent spontaneous catagen induction was observed both
      histologically and by the actual regression of the hair follicle. In addition,
      vellus follicles were shown to be viable at day 40 after initiation of culture.
      Follicle keratinocytes continued to incorporate [3H]thymidine for up to several
      weeks after shaft elongation had ceased. Intensive hair growth was observed in
      the pieces of shaved mouse skin histocultured on Gelfoam(r). Isolated human and
      mouse hair follicles also produced growing hair shafts. By day 63 in histoculture
      of mouse hair follicles, the number of hair follicle-associated pluripotent (HAP)
      stem cells increased significantly and the follicles were intact. Gelfoam(r)
      histoculture of skin demonstrated that the hair follicle cells are the most
      sensitive to doxorubicin which prevented hair growth, thereby mimicking
      chemotherapy-induced alopecia in Gelfoam(r) histoculture.

PMID- 29572802
TI  - Hair Follicle-Associated Pluripotent (HAP) Stem Cells in Gelfoam(r) Histoculture
      for Use in Spinal Cord Repair.
AB  - The stem cell marker, nestin, is expressed in the hair follicle, both in cells in
      the bulge area (BA) and the dermal papilla (DP). Nestin-expressing hair follicle
      associated-pluripotent (HAP) stem cells of both the BA and DP have been
      previously shown to be able to form neurons, heart muscle cells, and other non
      follicle cell types. The ability of the nestin-expressing HAP stem cells from the
      BA and DP to repair spinal cord injury was compared. Nestin-expressing HAP stem
      cells from both the BA and DP grew very well on Gelfoam(r). The HAP stem cells
      attached to the Gelfoam(r) within 1 h. They grew along the grids of the
      Gelfoam(r) during the first 2 or 3 days. Later they spread into the Gelfoam(r).
      After transplantation of Gelfoam(r) cultures of nestin-expressing BA or DP HAP
      stem cells into the injured spinal cord (including the Gelfoam(r)) nestin
      expressing BA and DP cells were observed to be viable over 100 days post-surgery.
      Hematoxylin and eosin (H&E) staining showed connections between the transplanted
      cells and the host spine tissue. Immunohistochemistry showed many Tuj1-, Isl 1/2,
      and EN1-positive cells and nerve fibers in the transplanted area of the spinal
      cord after BA Gelfoam(r) or DP Gelfoam(r) cultures were transplanted to the
      spine. The spinal cord of mice was injured to effect hind-limb paralysis. Twenty
      eight days after transplantation with BA or DP HAP stem cells on Gelfoam(r) to
      the injured area of the spine, the mice recovered normal locomotion.

PMID- 29572803
TI  - Nerve Growth and Interaction in Gelfoam(r) Histoculture: A Nervous System
      Organoid.
AB  - Nestin-expressing hair follicle-associated pluripotent (HAP) stem cells reside
      mainly in the bulge area (BA) of the hair follicle but also in the dermal papilla
      (DP). The BA appears to be origin of HAP stem cells. Long-term Gelfoam(r)
      histoculture was established of whiskers isolated from transgenic mice, in which
      there is nestin-driven green fluorescent protein (ND-GFP). HAP stem cells
      trafficked from the BA toward the DP area and extensively grew out onto
      Gelfoam(r) forming nerve-like structures. These fibers express the neuron marker
      beta-III tubulin-positive fibers and consisted of ND-GFP-expressing cells and
      extended up to 500 mm from the whisker nerve stump in Gelfoam(r) histoculture.
      The growing fibers had growth cones on their tips expressing F-actin indicating
      that the fibers were growing axons. HAP stem cell proliferation resulted in
      elongation of the follicle nerve and interaction with other nerves in 3D
      Gelfoam(r) histoculture, including the sciatic nerve, trigeminal nerve, and
      trigeminal nerve ganglion.

PMID- 29572804
TI  - Histoculture and Infection with HIV of Functional Human Lymphoid Tissue on
      Gelfoam(r).
AB  - Gelfoam(r) histoculture provides a valuable tool for experimental studies of
      normal and pathological tissue physiology. It allows us to understand cell-cell
      interactions by mirroring their original spatial relationship within body
      tissues. Gelfoam(r) histoculture can be employed to model host-pathogen
      interactions mimicking in vivo conditions in vitro. In the present chapter, we
      describe a protocol to process and infect lymphoid tissue explants with HIV and
      maintain them in Gelfoam(r) histoculture at the liquid-air interface. The
      Gelfoam(r) histocultures with human immunodeficiency virus (HIV) type 1-infected
      tissues have been used to further understand the biology of early HIV-1
      pathogenesis, as well as a novel ex vivo platform to test the efficacy and
      toxicity of antiviral drugs.

PMID- 29572805
TI  - Imaging DNA Repair After UV Irradiation Damage of Cancer Cells in Gelfoam(r)
      Histoculture.
AB  - DNA damage repair in response to UVC irradiation was imaged in cancer cells
      growing in Gelfoam(r) histoculture. UVC-induced DNA damage repair was imaged with
      green fluorescent protein (GFP) fused to the DNA damage response (DDR)-related
      binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. Three
      dimensional Gelfoam(r) histocultures and confocal imaging enabled 53BP1-GFP
      nuclear foci to be observed within 1 h after UVC irradiation, indicating the
      onset of DNA damage repair response. Induction of UV-induced 53BP1-GFP focus
      formation was limited up to a depth of 40 MUm in Gelfoam(r) histoculture of
      MiaPaCa-2 cells, indicating this was the depth limit of UVC irradiation.

PMID- 29572806
TI  - Comparison of "Dimensionality" of Cancer Cell Culture in Gelfoam(r) Histoculture
      and Matrigel.
AB  - Cell and tissue culture can be performed on different substrates such as on
      plastic, in MatrigelTM, and on Gelfoam(r), a sponge matrix. Each of these
      substrates consists of a very different surface, ranging from hard and
      inflexible, a gel, and a sponge-matrix, respectively. Folkman and Moscona found
      that cell shape was tightly coupled to proper gene expression. The flexibility of
      a substrate is important for cells to maintain their optimal shape. Human
      osteosarcoma cells, stably expressing a fusion protein of av integrin, and green
      fluorescent protein (GFP), grew as a simple monolayer without any structure
      formation on the surface of a plastic dish. When the osteosarcoma cells were
      cultured within Matrigel, the cancer cells formed colonies but no other
      structures. When the cancer cells were seeded on Gelfoam(r), the cells formed 3
      dimensional tissue-like structures. These results indicate that Gelfoam(r)
      histoculture, unlike MatrigelTM culture, is true 3-dimensional.

PMID- 29572807
TI  - Imaging the Governing Step of Metastasis in Gelfoam(r) Histoculture.
AB  - Distant organ colonization by cancer cells is the governing step of metastasis.
      We review in this chapter the modeling and imaging of organ colonization by
      cancer cells in Gelfoam(r) histoculture. ANIP 973 lung cancer cells expressing
      green fluorescent protein (GFP) were injected intravenously into nude mice,
      whereby they formed brilliantly fluorescing metastatic colonies on the mouse
      lung. The seeded lung tissue was then excised and incubated in the three
      dimensional Gelfoam(r) histoculture that maintained the critical features of
      progressive in vivo organ colonization. Tumor progression was continuously
      visualized by GFP fluorescence of individual cultures over a 52-day period,
      during which tumor colonies spread throughout the lung. Organ colonization was
      selective in Gelfoam(r) histoculture for lung cancer cells to grow on lung
      tissue, since no growth occurred on histocultured mouse liver tissue. The ability
      to support selective organ colonization in Gelfoam(r) histoculture and visualize
      tumor progression by GFP fluorescence allows the in vitro study of the governing
      processes of metastasis.

PMID- 29572808
TI  - Readmission and complications within 30 days after intrathecal baclofen pump
      placement.
AB  - AIM: To describe 30-day outcomes after intrathecal baclofen (ITB) pump placement
      in children and identify risk factors for readmission, reoperation, and
      perioperative complication using the National Surgical Quality Improvement
      Program-Pediatric (NSQIP-P) database. METHOD: Patients aged 0 to 18 years who
      underwent ITB pump placement (2012-2014) comprised the study cohort defined in
      the database. Multivariate regression analysis was performed using preoperative
      and perioperative data from the American College of Surgeons' NSQIP-P database.
      Outcomes of interest within 30 days of surgery were (1) unplanned reoperation;
      (2) unplanned readmission; and (3) composite postoperative event, including
      complication, reoperation, and/or readmission. RESULTS: We identified 423
      surgeries; 246 (58.2%) patients were male, 177 (41.8%) patients were female.
      Median age was 12 years and 11 months. Median operative time was 70 minutes
      (interquartile range 56-97min). Mean length of stay was 3.8 days. The patient
      population had a high number of medical comorbidities. The overall readmission
      rate was 7.3%; mean postoperative admission date was 14.1 days after surgery. Of
      readmitted patients, 64.5% underwent reoperation. The most common indication for
      reoperation was surgical site infection. Female sex was associated with decreased
      risk of readmission (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.09
      0.65; p=0.01); American Society of Anesthesiologists Classification of greater
      than or equal to 3 was associated with decreased risk of unplanned return to
      surgery (OR 0.26, 95% CI 0.11-0.66; p=0.04); length of stay greater than or equal
      to 3 days at index surgery was associated with increased risk of composite 30-day
      perioperative event (OR 2.33, 95% CI 1.29-4.20; p=0.01). INTERPRETATION: Our data
      provide national perspectives on 30-day perioperative outcomes for ITB pump
      placement in children. Results illustrate NSQIP-P database collection methodology
      and highlight opportunities for quality improvement in clinical practice. WHAT
      THIS PAPER ADDS: Seven percent of patients who underwent intrathecal baclofen
      pump placement required readmission within 30 days. The most common indication
      for reoperation was surgical site infection.

PMID- 29572809
TI  - PLZF-expressing CD4 T cells show the characteristics of terminally differentiated
      effector memory CD4 T cells in humans.
AB  - We show the presence of lymphoid tissue-resident PLZF+ CD45RA+ RO+ CD4 T cells in
      humans. They express HLA-DR, granzyme B, and perforin and are low on CCR7 like
      terminally differentiated effector memory (Temra) cells and are likely generated
      from effector T cells (Te) or from central (Tcm) or effector (Tem) memory T (Tcm)
      cells during immune responses. Tn, Naive T cells.

PMID- 29572810
TI  - Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic
      activity.
AB  - MS and EAE are T cell-driven autoimmune diseases of the CNS where IL-17-producing
      Th17 cells promote damage and are pathogenic. Conversely, tolerogenic DCs induce
      Treg cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the
      modulation of DCs by unknown mechanisms. Here, we show that STAT 1 is necessary
      for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE. We observed
      that CQ induces phosphorylation of STAT1 in DCs in vivo and in vitro. Genetic
      blockage of STAT1 abrogated the suppressive activity of CQ-treated DCs. Opposed
      to its WT counterparts, CQ-treated STAT1-/- BMDCs were unable to suppress Th17
      cells and increased EAE severity. Our findings show that STAT1 is a major
      signaling pathway in CQ-induced tolDCs and may shed light on new therapeutic
      avenues for the induction of tolDCs in autoimmune diseases such as MS.

PMID- 29572811
TI  - Teledermatologist expert skin advice: A unique model of care for managing skin
      disorders and adverse drug reactions in hepatitis C patients.
AB  - OBJECTIVES: To conduct an audit of teledermatologist expert skin advice, a store
      and forward tele-dermatological service, to determine its effectiveness and user
      satisfaction in managing cutaneous adverse drug reactions in patients with
      hepatitis C, and to demonstrate a unique collaborative model of care for patients
      receiving specialised drug therapy. METHODS: A retrospective analysis of data on
      teledermatologist expert skin advice referrals from January 2014 to December 2015
      was performed. The primary outcomes assessed included number of referrals,
      referral locations, diagnoses, response times, quality of clinical information
      provided and user satisfaction ratings. RESULTS: Altogether 43 consultations from
      29 referring sites were received from Australian metropolitan and rural settings.
      Of the patients, 43 were diagnosed with an adverse drug reaction related to the
      use of either telaprevir or simeprevir. The average time taken for the
      dermatologist to reply electronically with a final diagnosis and management plan
      was 1 h 57 min. As many as 26% of referrals required additional photos to
      establish a diagnosis due to poor-quality images or insufficient detail.
      Altogether 18 clinicians completed the customer satisfaction survey, all of whom
      rated teledermatologist expert skin advice nine or above on a scale of one to 10.
      CONCLUSIONS: Teledermatologist expert skin advice was regarded by clinicians as a
      valuable patient care service. The platform is a novel modality that supports
      patients undergoing specialised treatments at risk of cutaneous adverse drug
      reaction.

PMID- 29572812
TI  - The risk, burden, and management of non-communicable diseases in cerebral palsy:
      a scoping review.
AB  - AIM: To examine the risk, burden, and management of non-communicable diseases
      (NCDs) among people with cerebral palsy (CP). METHOD: Databases (Ovid MEDLINE,
      Embase Ovid, CINAHL Plus) were systematically searched up to August 2017. Data on
      the prevalence of risk factors for, and the burden and management of,
      cardiovascular diseases, diabetes, cancers, and respiratory diseases were
      extracted. RESULTS: Thirty-six studies that examined the prevalence of risk
      factors among people with CP were identified. There was inconsistent evidence
      that people with CP had higher prevalence of metabolic risk factors such as
      hypertension, hyperlipidaemia, and obesity, but strong evidence that they
      participated in low levels of physical activity, compared with people without CP.
      Seven studies reported on the burden of NCDs. Adults with CP had a higher risk of
      NCDs, including stroke, chronic obstructive pulmonary disease, and other heart
      conditions, and death due to NCDs, including cancers, chronic obstructive
      pulmonary disease, stroke, and ischaemic heart disease, compared with the general
      population. Only one study reported on the management of NCD, specifically the
      uptake of breast cancer screening among females. INTERPRETATION: The burden of
      NCDs is higher among adults with CP compared with the general population. Further
      research is required to determine the prevalence of metabolic risk factors and
      management of NCDs among people with CP. WHAT THIS PAPER ADDS: Adults with
      cerebral palsy (CP) have an increased risk of non-communicable diseases (NCDs)
      and increased risk of death because of NCDs. Evidence is inconsistent about the
      elevated prevalence of metabolic risk factors for NCDs. Evidence is consistent
      that people with CP participate in reduced physical activity. Only one study
      reported on management of NCD among people with CP. Available evidence suggests
      people with CP are less likely to receive preventive medicine.

PMID- 29572813
TI  - The validity of caries risk assessment in young adults with past caries
      experience using a screening Cariogram model without saliva tests.
AB  - OBJECTIVE: To evaluate the caries-predictive validity of a screening Cariogram
      model without saliva tests in Chinese young adults with past caries experience.
      METHODS: Two-hundred and fifteen Chinese young adults seeking dental care were
      included in this observational study, with informed consent obtained. All
      participants were 18-29 years of age and with past caries experience. A caries
      risk assessment was made at baseline using a full-blown Cariogram model and a
      screening Cariogram model without saliva tests; this assessment included
      bacterial count, saliva secretion and buffer capacity. Participants were divided
      into five risk groups according to 'the chance of avoiding caries' expressed in
      Cariogram software with two models. Each participant was required to receive re
      examination after 2 years and then the actual caries increment (DeltaDMFS) was
      calculated. The correlation between DeltaDMFS and the ratings of caries risk was
      analysed using Spearman rank correlation. Differences between the full-blown and
      screening models were expressed as area under the receiver-operating
      characteristics (ROC) curve (AUC). RESULTS: One-hundred and ninety-two
      participants finished the 2-year follow-up study, after 23 dropped out. The mean
      2-year caries increment was 0.67 +/- 1.03. Both Cariogram models displayed a
      statistically significant relationship with caries development (P < 0.001): more
      new caries was found among those assessed with high risk compared with those
      assessed with low risk. No statistically significant difference of the AUC was
      found between the two Cariogram models (P > 0.05). CONCLUSIONS: The Cariogram
      model without saliva tests does not significantly decrease the caries-predictive
      ability in young adults with a history of caries. This screening model is a
      potential tool for rapid caries risk assessment for such populations.

PMID- 29572814
TI  - A Person-Centered Approach to Poststroke Care: The COMprehensive Post-Acute
      Stroke Services Model.
AB  - Many individuals who have had a stroke leave the hospital without postacute care
      services in place. Despite high risks of complications and readmission, there is
      no standard in the United States for postacute stroke care after discharge home.
      We describe the rationale and methods for the development of the COMprehensive
      Post-Acute Stroke Services (COMPASS) care model and the structure and quality
      metrics used for implementation. COMPASS, an innovative, comprehensive extension
      of the TRAnsition Coaching for Stroke (TRACS) program, is a clinician-led quality
      improvement model providing early supported discharge and transitional care for
      individuals who have had a stroke and have been discharged home. The
      effectiveness of the COMPASS model is being assessed in a cluster-randomized
      pragmatic trial in 41 sites across North Carolina, with a recruitment goal of
      6,000 participants. The COMPASS model is evidence based, person centered, and
      stakeholder driven. It involves identification and education of eligible
      individuals in the hospital; telephone follow-up 2, 30, and 60 days after
      discharge; and a clinic visit within 14 days conducted by a nurse and advanced
      practice provider. Patient and caregiver self-reported assessments of functional
      and social determinants of health are captured during the clinic visit using a
      web-based application. Embedded algorithms immediately construct an
      individualized care plan. The COMPASS model's pragmatic design and quality
      metrics may support measurable best practices for postacute stroke care.

PMID- 29572815
TI  - Single, short in-del, and copy number variations detection in monogenic
      dyslipidemia using a next-generation sequencing strategy.
AB  - Optimal molecular diagnosis of primary dyslipidemia is challenging to confirm the
      diagnosis, test and identify at risk relatives. The aim of this study was to test
      the application of a single targeted next-generation sequencing (NGS) panel for
      hypercholesterolemia, hypocholesterolemia, and hypertriglyceridemia molecular
      diagnosis. NGS workflow based on a custom AmpliSeq panel was designed for
      sequencing the most prevalent dyslipidemia-causing genes (ANGPTL3, APOA5, APOC2,
      APOB, GPIHBP1, LDLR, LMF1, LPL, PCSK9) on the Ion PGM Sequencer. One hundred and
      forty patients without molecular diagnosis were studied. In silico analyses were
      performed using the NextGENe software and homemade tools for detection of copy
      number variations (CNV). All mutations were confirmed using appropriate tools.
      Eighty seven variations and 4 CNV were identified, allowing a molecular diagnosis
      for 40/116 hypercholesterolemic patients, 5/13 hypocholesterolemic patients, and
      2/11, hypertriglyceridemic patients respectively. This workflow allowed the
      detection of CNV contrary to our previous strategy. Some variations were found in
      previously unexplored regions providing an added value for genotype-phenotype
      correlation and familial screening. In conclusion, this new NGS process is an
      effective mutation detection method and allows better understanding of phenotype.
      Consequently this assay meets the medical need for individualized diagnosis of
      dyslipidemia.

PMID- 29572816
TI  - Pseudomonas aeruginosa rhamnolipid induces fibrillation of human alpha-synuclein
      and modulates its effect on biofilm formation.
AB  - The Parkinson's disease-associated protein alpha-synuclein (alphaSN) is natively
      unfolded but its structure can be modulated by membranes and surfactants. The
      opportunistic pathogen Pseudomonas aeruginosa (PA) produces and secretes the
      biosurfactant rhamnolipid (RL) which modulates bacterial biofilm. Here, we show
      that monomeric RL enhances the ability of alphaSN to permeabilize membranes,
      while micellar RL rapidly induces protein beta-sheet structure with a worm-like
      fibrillary appearance, which cannot seed RL-free fibrillation but transforms into
      linear fibrils faster than alphaSN fibrillating on its own. Exposure to alphaSN
      reduces the degree of biofilm formation by PA unless RL is present. Our data
      suggest that RL interactions with alphaSN may affect both alphaSN aggregation and
      cell toxicity, potentially implicating microbiomic metabolites in the origin and
      propagation of Parkinson's disease.

PMID- 29572817
TI  - Tetramer-based identification of naive antigen-specific B cells within a
      polyclonal repertoire.
AB  - Detecting naive antigen-specific B cells can be challenging. Use of multiple,
      complementary tetramers with different fluorochromes enhances sensitivity and
      specificity allowing naive antigen-specific B cells to be readily distinguished
      within a polyclonal repertoire. Activated, affinity-matured B cells, however, can
      be detected effectively using a single tetramer.

PMID- 29572818
TI  - Actinic Keratosis Area Severity Index (AKASI): reproducibility study and
      comparison with total lesion count.

PMID- 29572819
TI  - Two distinct glyceraldehyde-3-phosphate dehydrogenases in glycolysis and
      gluconeogenesis in the archaeon Haloferax volcanii.
AB  - The halophilic archaeon Haloferax volcanii degrades glucose via the
      semiphosphorylative Entner-Doudoroff pathway and can also grow on gluconeogenic
      substrates. Here, the enzymes catalysing the conversion of glyceraldehyde-3
      phosphate (GAP) to 3-phosphoglycerate were analysed. The genome contains the
      genes gapI and gapII encoding two putative GAP dehydrogenases, and pgk encoding
      phosphoglycerate kinase (PGK). We show that gapI is functionally involved in
      sugar catabolism, whereas gapII is involved in gluconeogenesis. For pgk, an
      amphibolic function is indicated. This is the first report of the functional
      involvement of a phosphorylating glyceraldehyde-3-phosphate dehydrogenase and PGK
      in sugar catabolism in archaea. Phylogenetic analyses indicate that the catabolic
      gapI from H. volcanii is acquired from bacteria via lateral genetransfer, whereas
      the anabolic gapII as well as pgk are of archaeal origin.

PMID- 29572820
TI  - Semantic and Phonemic Verbal Fluency Discrepancy in Mild Cognitive Impairment:
      Potential Predictor of Progression to Alzheimer's Disease.
AB  - OBJECTIVES: To assess the utility of verbal fluency discrepancy scores in
      predicting progression to Alzheimer's disease (AD) in a cohort of individuals
      with mild cognitive impairment (MCI). DESIGN: Case control. SETTING: Cases
      identified from new referrals to a memory clinic and controls identified from The
      Irish Longitudinal Study on Ageing. PARTICIPANTS: Of 308 individuals with MCI at
      baseline identified from consecutive referrals to a memory clinic and compared at
      with age-, sex-, and education-matched controls (n=302), 161 completed 2 years of
      follow-up or progressed to AD during the study period. MEASUREMENTS: Verbal
      fluency discrepancy (semantic-phonemic fluency) scores at baseline were
      calculated for each participant. Each case was followed with repeated
      neuropsychological measurements, and multidisciplinary consensus diagnosis was
      recorded. RESULTS: Mean discrepancy score for those who progressed to AD (2.7)
      was significantly lower than for those who retained a MCI diagnosis (4.8) and
      normal controls (7.7) (p<.001). Logistic regression revealed that, for each unit
      decrease in discrepancy score at baseline, the odds of progressing to AD were 9%
      greater. (Exp(B) = 1.09, p=.02) CONCLUSION: Individuals with MCI have less of a
      semantic advantage than those without MCI. Those with MCI presenting with a
      phonemic advantage at initial assessment warrant close follow-up and a high index
      of suspicion for progression to AD.

PMID- 29572821
TI  - Perioperative neonatal brain injury is associated with worse school-age
      neurodevelopment in children with critical congenital heart disease.
AB  - AIM: To assess the impact of perioperative neonatal brain injury and brain
      volumes on neurodevelopment throughout school-age children with critical
      congenital heart disease (CHD). METHOD: Thirty-four survivors of neonatal cardiac
      surgery (seven females, 27 males) were included. Neonatal preoperative and
      postoperative cerebral magnetic resonance imaging was performed and
      neurodevelopment was assessed at 24 months (SD 0.7, n=32, using Bayley Score of
      Infant and Toddler Development, Child Behavior Checklist) and 6 years (mean age
      5y 11mo; SD 0.3, n=30, using Movement Assessment Battery for Children, Wechsler
      Preschool and Primary Scale of Intelligence, Child Behavior Checklist, Teacher
      Report Form). Brain injury, brain volumes, and cortical measures were related to
      outcome with adjustment for maternal educational level. RESULTS: Two-year
      cognitive score and 6-year Full-scale IQ were poorer in children with neonatal
      white matter injury (n=21, all p<0.05), with higher teacher-reported attention
      problems (p=0.03). Five of six children with involvement of the posterior limb of
      the internal capsule showed motor problems (p=0.03). Children with a below
      average Fulll-scale IQ (<85, n=9) showed smaller volumes of basal ganglia thalami
      (-8%, p=0.03) and brain stem (-7%, p=0.03). INTERPRETATION: Our findings provide
      evidence of unfavourable outcome in school-age children with critical CHD who
      acquire perioperative neonatal brain injury. WHAT THIS PAPER ADDS: This paper
      extends knowledge about neonatal brain injury and long-term outcome in congenital
      heart disease. Children with white matter injury show lower IQ and more attention
      problems at school age. Injury of the posterior limb of the internal capsule
      increases the risk of motor problems. This study provides evidence for worse
      outcomes in neonates acquiring brain injury around cardiac surgery.

PMID- 29572822
TI  - Methotrexate restores the function of peripheral blood regulatory T cells in
      psoriasis vulgaris via the CD73/AMPK/mTOR pathway.
AB  - BACKGROUND: Methotrexate (MTX) is used to treat psoriasis, a chronic inflammatory
      skin disease. OBJECTIVES: To investigate the molecular mechanism of MTX in the
      treatment of psoriasis. METHODS: Regulatory T cells (Tregs) and effector T (Teff)
      cells were isolated from the blood of patients with psoriasis and healthy
      controls. The proliferation of Teff cells was detected by carboxyfluorescein
      succinimidyl ester assay. The interferon (IFN)-gamma and interleukin (IL)-17
      levels were analysed by enzyme-linked immunosorbent assay. The expression of CD73
      and FoxP3 were determined by flow cytometry. The expression of proteins in the
      AMPK/mTOR pathway were detected by Western blot analysis. RESULTS: The data
      suggested that patients with psoriasis have Tregs with decreased immune
      suppression function and reduced expression of CD73 compared with healthy
      controls. Moreover, MTX could significantly restore the immunosuppressive
      function of IL-17-secreting Tregs. This, in turn, inhibits aberrant proliferation
      of Teff cells in patients with psoriasis, reverses downregulation of CD73,
      upregulates phosphorylated AMPK and inhibits phosphorylated mTOR, and
      downregulates IL-17 and IFN-gamma levels. CONCLUSIONS: We speculate that MTX can
      restore the immunosuppressive function of Tregs through upregulating CD73,
      activating AMPK and inactivating the mTOR pathway. These findings may partly
      explain the mechanism by which MTX treats psoriasis.

PMID- 29572823
TI  - A systematic review and meta-analysis of velamentous cord insertion among
      singleton pregnancies and the risk of preterm delivery.
AB  - BACKGROUND: Observational studies have reported varying results about the
      association of velamentous cord insertion (VCI) with adverse pregnancy outcomes.
      OBJECTIVES: To evaluate the risk of preterm delivery among singleton pregnancies
      complicated by VCI. SEARCH STRATEGY: Various databases were searched for English
      language articles published up to February, 28, 2017, using keywords including
      VCI; abnormal placentation; abnormal cord insertions; adverse perinatal outcomes;
      and preterm birth. Outcome measures included preterm delivery; pre-eclampsia;
      cesarean delivery; fetal demise in utero (FDIU); and small for gestational age
      (SGA). SELECTION CRITERIA: Only studies involving VCI were included in the meta
      analysis. DATA COLLECTION AND ANALYSIS: Analyses were performed using RevMan
      version 5.3.5 (The Nordic Cochrane Centre, Copenhagen, Denmark). MAIN RESULTS:
      There were six studies included in the analysis. The VCI and control groups
      comprised 16 295 and 1 366 485 women, respectively. An increased incidence of
      preterm delivery was found for the VCI group compared with the control group
      (11.8% vs 7.0%; adjusted odds ratio [aOR] 1.95, 95% confidence interval [CI] 1.85
      2.04). A diagnosis of VCI was also associated with cesarean delivery (aOR 1.17,
      95% CI 1.12-1.23), SGA (aOR 1.93, 95% CI 1.83-2.04), and FDIU (aOR 3.96, 95% CI
      3.21-4.89). CONCLUSION: The presence of VCI was associated with adverse pregnancy
      outcomes.

PMID- 29572824
TI  - Vascularized lymph node transfer for treatment of extremity lymphedema: An
      overview of current controversies regarding donor sites, recipient sites and
      outcomes.
AB  - As lymphatic microsurgery has become more common, vascularized lymph node
      transfer ascended to the forefront in many centers for the surgical management of
      advanced stages of lymphedema showing substantial clinical improvement. However,
      no consensus has been reached among experts regarding many details of the
      procedures, including patient selection criteria, type of treatment, donor, and
      recipient sites and postoperative evaluation of the outcome. Here, we will review
      these issues and provide the current results of this procedure.

PMID- 29572825
TI  - New onset non-alcoholic fatty liver disease after resection of pancreatic
      neuroendocrine tumors.
AB  - BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and non
      alcoholic steatohepatis (NASH) may occur after pancreatic resection due to
      exocrine pancreatic insufficiency (EPI). Patients with long-term survival, such
      as after pancreatic neuroendocrine tumor (pNET) resection, are at risk of
      NAFLD/NASH. We aimed to determine the incidence and risk factors for new onset
      NAFLD/NASH and EPI after pNET resection. METHODS: Retrospective monocenter cohort
      study. Patients who underwent pNET resection (1992-2016) were assessed for new
      onset NAFLD/NASH and EPI. Postoperative NAFLD/NASH was determined by a blinded
      abdominal radiologist, who compared pre- and postoperative imaging. RESULTS: Out
      of 235 patients with pNET, a total of 112 patients underwent resection and were
      included with a median follow-up of 54 months. New onset NAFLD/NASH occurred in
      20% and EPI in 49% of patients. Multivariate analysis showed that the only risk
      factor for new onset NAFLD/NASH was recurrent disease (OR 4.4, 95% CI 1.1-16.8, P
      = 0.031), but not EPI (OR 0.94, 95% CI 0.3-2.8, P = 0.911). The only risk factor
      for EPI was pancreatoduodenectomy (OR 4.3, 95% CI 1.4-13.7, P = 0.012).
      CONCLUSIONS: New onset NAFLD/NASH is occasionally found after pNET resection,
      especially in patients with recurrent disease, but is not related to EPI.

PMID- 29572826
TI  - Differential effects of vision upon the accuracy and precision of vestibular
      evoked balance responses.
AB  - KEY POINTS: Effective balance control requires the transformation of vestibular
      signals from head- to foot-centred coordinates in order to move the body in an
      appropriate direction. This transformation process has previously been studied by
      analysing the directional accuracy of the averaged sway response to multiple
      electrical vestibular stimuli (EVS). Here we studied trial-by-trial variability
      of EVS responses to measure any changes in directional precision which may be
      masked by the averaging process. We found that vision increased directional
      variability without influencing the mean sway direction, demonstrating that
      response accuracy and precision are dissociable. These results emphasise the
      importance of single trial analysis in determining the efficacy of vestibular
      control of balance. ABSTRACT: Vestibular information must be transformed from
      head- to-foot-centred coordinates for balance control. This transformation
      process has previously been investigated using electrical vestibular stimulation
      (EVS), which evokes a sway response fixed in head coordinates. The craniocentric
      nature of the response has been demonstrated by analysing average responses to
      multiple stimuli. This approach misses any trial-by-trial variability which would
      reflect poor balance control. Here we performed single-trial analysis to measure
      this directional variability (precision), and compared this to mean performance
      (accuracy). We determined the effect of vision upon both parameters. Standing
      volunteers adopted various head orientations (0, +/-30 and +/-60 deg yaw) while
      EVS-evoked response direction was determined from ground reaction force vectors.
      As previously reported, mean force direction was orientated towards the anodal
      ear, and rotated in line with head yaw. Although vision caused a ~50% reduction
      in response magnitude, it had no influence on the direction of the mean sway
      response, indicating that accuracy was unaffected. However, individual trial
      analysis revealed up to 30% increases in directional variability with the eyes
      open. This increase was inversely correlated with the size of the force response.
      The paradoxical observation that vision reduces the precision of the balance
      response may be explained by a multi-sensory integration process. As additional
      veridical sensory information becomes available, this lessens the relative
      contribution of vestibular input, causing a simultaneous reduction in both the
      magnitude and the precision of the response to EVS. Our novel approach
      demonstrates the importance of single-trial analysis in revealing the efficacy of
      vestibular reflexes.

PMID- 29572827
TI  - Activity-dependent synaptic integration and modulation of bilateral excitatory
      inputs in an auditory coincidence detection circuit.
AB  - KEY POINTS: Binaural excitatory inputs to coincidence detection neurons in
      nucleus laminaris (NL) play essential roles in interaural time difference coding
      for sound localization. Here, we show that the two excitatory inputs are
      physiologically nearly completely segregated. Synaptic integration shows linear
      summation of EPSPs, ensuring high efficiency of coincidence detection of the
      bilateral excitatory inputs. We further show that the two excitatory inputs to
      single NL neurons are symmetrical in synaptic strength, kinetics and short-term
      plasticity. Modulation of the EPSCs by metabotropic glutamate receptors (mGluRs)
      is identical between the two excitatory inputs, maintaining balanced bilateral
      excitation under neuromodulatory conditions. Unilateral hearing deprivation
      reduces synaptic excitation and paradoxically strengthens mGluR modulation of
      EPSCs, suggesting activity-dependent anti-homeostatic regulation, a novel
      synaptic plasticity in response to sensory manipulations. ABSTRACT: Neurons in
      the avian nucleus laminaris (NL) receive bilateral excitatory inputs from the
      cochlear nucleus magnocellularis, via morphologically symmetrical dorsal
      (ipsilateral) and ventral (contralateral) dendrites. Using in vitro whole-cell
      patch recordings in chicken brainstem slices, we investigated synaptic
      integration and modulation of the bilateral inputs to NL under normal and hearing
      deprivation conditions. We found that the two excitatory inputs onto single NL
      neurons were nearly completely segregated, and integration of the two inputs was
      linear for EPSPs. The two inputs had similar synaptic strength, kinetics and
      short-term plasticity. EPSCs in low but not middle and high frequency neurons
      were suppressed by activation of group I and II metabotropic glutamate receptors
      (mGluR I and II), with similar modulatory strength between the ipsilateral and
      contralateral inputs. Unilateral hearing deprivation by cochlea removal reduced
      the excitatory transmission on the deprived dendritic domain of NL.
      Interestingly, EPSCs evoked at the deprived domain were modulated more strongly
      by mGluR II than at the counterpart domain that received intact input in low
      frequency neurons, suggesting anti-homeostatic regulation. This was supported by
      a stronger expression of mGluR II protein on the deprived neuropils of NL. Under
      mGluR II modulation, EPSCs on the deprived input show transient synaptic
      facilitation, forming a striking contrast with normal hearing conditions under
      which pure synaptic depression is observed. These results demonstrate
      physiological symmetry and thus balanced bilateral excitatory inputs to NL
      neurons. The activity-dependent anti-homeostatic plasticity of mGluR modulation
      constitutes a novel mechanism regulating synaptic transmission in response to
      sensory input manipulations.

PMID- 29572828
TI  - The prognostic impact of differentiation at the invasive front of biliary tract
      cancer.
AB  - BACKGROUND: The invasive front of tumor can provide prognostic information in
      many cancers. We investigated the prognostic morphological factors at the
      invasive front including tumor differentiation (Difinv ) and tumor budding (Bud)
      in biliary tract cancer (BTC). METHODS: The resected specimen from the 299 BTC
      patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic
      cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in
      16%, 48%, 17%, and 19%, respectively. Difinv grade (G) 3 and Bud foci >=5 were
      found in 47% and 10%. Tumor with Difinv G3 showed the high frequencies of Bud,
      vascular invasion (Ve) and nodal metastasis (LN) compared to tumor with Difinv
      G1/2 (Bud: 21% vs 0%, Ve: 71% vs 50%, LN: 52% vs 36%). Multivariate analysis
      revealed that the independent predictors were Difinv G3 (HR: 1.71), Bud foci >=5
      (HR: 2.14), Ve (HR: 1.56) and LN (HR: 2.59) in overall survival and were positive
      resection margin (HR: 1.71), Difinv G3 (HR: 1.75), Ve (HR: 1.50), and LN (HR:
      2.19) in relapse free survival. CONCLUSION: Poor differentiation at the invasive
      front of tumor was associated with poor prognosis and early relapse in BTC
      patients.

PMID- 29572830
TI  - Overview on mitigation of acrylamide in starchy fried and baked foods.
AB  - Acrylamide in fried and baked foods has the potential to cause toxic effects in
      animals and humans. A major challenge lies in developing an effective strategy
      for acrylamide mitigation in foods without altering its basic properties. Food
      scientists around the world have developed various methods to mitigate the
      presence of acrylamide in fried food products. Mitigation techniques using
      additives such as salts, amino acids, cations and organic acids along with
      blanching of foods have reduced the concentration of acrylamide. The use of
      secondary metabolites such as polyphenols also reduces acrylamide concentration
      in fried food products. Other mitigation techniques such as asparaginase pre
      treatment and low-temperature air frying with chitosan have been effective in
      mitigating the concentration of acrylamide. The combined pre-treatment process
      along with the use of additives is the latest trend in acrylamide mitigation. (c)
      2018 Society of Chemical Industry.

PMID- 29572829
TI  - Time and sex dependent effects of magnesium sulphate on post-asphyxial seizures
      in preterm fetal sheep.
AB  - KEY POINTS: We evaluated the effect of magnesium sulphate (MgSO4 ) on seizures
      induced by asphyxia in preterm fetal sheep. MgSO4 did not prevent seizures, but
      significantly reduced the total duration, number of seizures, seizure amplitude
      and average seizure burden. Saline-asphyxia male fetuses had significantly more
      seizures than female fetuses, but male fetuses showed significantly greater
      reduction in seizures during MgSO4 infusion than female fetuses. A circadian
      profile of seizure activity was observed in all fetuses, with peak seizures seen
      around 04.00-06.00 h on the first and second days after the end of asphyxia. This
      study is the first to demonstrate that MgSO4 has utility as an anti-seizure agent
      after hypoxia-ischaemia. More information is needed about the mechanisms
      mediating the effect of MgSO4 on seizures and sexual dimorphism, and the
      influence of circadian rhythms on seizure expression. ABSTRACT: Seizures are
      common in newborns after asphyxia at birth and are often refractory to anti
      seizure agents. Magnesium sulphate (MgSO4 ) has anticonvulsant effects and is
      increasingly given to women in preterm labour for potential neuroprotection.
      There is limited information on its effects on perinatal seizures. We examined
      the hypothesis that MgSO4 infusion would reduce fetal seizures after asphyxia in
      utero. Preterm fetal sheep at 0.7 gestation (104 days, term = 147 days) were
      given intravenous infusions of either saline (n = 14) or MgSO4 (n = 12, 160 mg
      bolus + 48 mg h-1 infusion over 48 h). Fetuses underwent umbilical cord occlusion
      (UCO) for 25 min, 24 h after the start of infusion. The start time for seizures
      did not differ between groups, but MgSO4 significantly reduced the total number
      of seizures (P < 0.001), peak seizure amplitude (P < 0.05) and seizure burden (P
      < 0.005). Within the saline-asphyxia group, male fetuses had significantly more
      seizures than females (P < 0.05). Within the MgSO4 -asphyxia group, although both
      sexes had fewer seizures than the saline-asphyxia group, the greatest effect of
      MgSO4 was on male fetuses, with reduced numbers of seizures (P < 0.001) and
      seizure burden (P < 0.005). Only 1 out of 6 MgSO4 males had seizures on the
      second day post-UCO compared to 5 out of 6 MgSO4 female fetuses (P = 0.08).
      Finally, seizures showed a circadian profile with peak seizures between 04.00 and
      06.00 h on the first and second day post-UCO. Collectively, these results suggest
      that MgSO4 may have utility in treating perinatal seizures and has sexually
      dimorphic effects.

PMID- 29572831
TI  - The impact of proteinuria on maternal and perinatal outcomes among women with pre
      eclampsia.
AB  - OBJECTIVE: To assess the impact of proteinuria on pregnancy outcomes among women
      with pre-eclampsia. METHODS: The present retrospective cohort study included
      patients with pre-eclampsia who delivered at a referral maternity hospital in
      Brazil between January 1, 2009, and December 31, 2013. Patients were stratified
      into three groups based on 24-hour urinary protein excretion during pregnancy:
      mild (0.3-<2.0 g), severe (2.0-<5.0 g), and massive (>=5.0 g). RESULTS: There
      were 293 patients included in the study; 88, 129, and 76 had mild, severe, and
      massive proteinuria, respectively. Chronic hypertension was the most frequent pre
      existing condition among all women (86 [29.4%]). The mean pregnancy duration at
      the onset of maternal pre-eclampsia was longest in the mild group compared and
      decreased with increasing proteinuria severity (P<0.001). Preterm delivery was
      recorded among 205 of 293 (70.0%) neonates; there were 66 (22.5%) neonates that
      were preterm and in the massive proteinuria group. The incidence of severe pre
      eclampsia was lowest in the mild proteinuria group (P=0.002) and tended to occur
      at 34 weeks. Cesarean delivery rates exceeded 80.0% in all groups. Most patients
      assessed at 40-60 days postpartum remained proteinuric (40/61[66%]). CONCLUSIONS:
      Quantifying the severity of proteinuria could identify a subgroup of women with
      pre-eclampsia at increased risk of adverse outcomes.

PMID- 29572832
TI  - When muscle Ca2+ channels carry monovalent cations through gating pores: insights
      into the pathophysiology of type 1 hypokalaemic periodic paralysis.
AB  - Patients suffering from type 1 hypokalaemic periodic paralysis (HypoPP1)
      experience attacks of muscle paralysis associated with hypokalaemia. The disease
      arises from missense mutations in the gene encoding the alpha1 subunit of the
      dihydropyridine receptor (DHPR), a protein complex anchored in the tubular
      membrane of skeletal muscle fibres which controls the release of Ca2+ from
      sarcoplasmic reticulum and also functions as a Ca2+ channel. The vast majority of
      mutations consist of the replacement of one of the outer arginines in S4 segments
      of the alpha1 subunit by neutral residues. Early studies have shown that muscle
      fibres from HypoPP1 patients are abnormally depolarized at rest in low K+ to the
      point of inducing muscle inexcitability. The relationship between HypoPP1
      mutations and depolarization has long remained unknown. More recent
      investigations conducted in the closely structurally related voltage-gated Na+
      and K+ channels have shown that comparable S4 arginine substitutions gave rise to
      elevated inward currents at negative potentials called gating pore currents.
      Experiments performed in muscle fibres from different models revealed such an
      inward resting current through HypoPP1 mutated Ca2+ channels. In mouse fibres
      transfected with HypoPP1 mutated channels, the elevated resting current was found
      to carry H+ for the R1239H arginine-to-histidine mutation in a S4 segment and Na+
      for the V876E HypoPP1 mutation, which has the peculiarity of not being located in
      S4 segments. Muscle paralysis probably results from the presence of a gating pore
      current associated with hypokalaemia for both mutations, possibly aggravated by
      external acidosis for the R1239H mutation.

PMID- 29572833
TI  - New nomogram predicts the recurrence of hepatocellular carcinoma in patients with
      negative preoperative serum AFP subjected to curative resection.
AB  - BACKGROUND: There is currently no established model for predicting the recurrence
      of hepatocellular carcinoma (HCC) in patients with negative alpha-fetoprotein
      (AFP) after curative resection. Therefore, the objective of this study was to
      establish a nomogram to identify the risk of recurrence in AFP-negative (<or = 20
      ng/mL) patients with HCC. METHODS: A retrospective study was conducted to
      establish the recurrence-free survival (RFS) nomogram in a training cohort of 326
      AFP-negative HCC patients. The results were validated on a well-matched
      validation cohort in the literature. RESULTS: Macrovascular tumour invasion (P =
      0.018, HR = 1.642), macronodular cirrhosis (P < 0.001, HR = 2.128), tumor size (P
      = 0.004, HR = 1.691), and gamma-glutamyl transferase (P = 0.039, HR = 1.496) were
      found to be independent risk factors for RFS in the training cohort, and all
      these factors were included in the nomogram. The C-index for RFS in the nomogram
      was 0.661, which was higher than that of the BCLC system (0.551), the CLIP score
      (0.537), and the prediction model of Ju (0.618). The high consistency between the
      nomogram prediction and actual observation was further demonstrated by the
      calibration curve. In the subsequent study, the better net benefit and higher
      threshold probability of the nomogram were determined by decision curve analysis,
      and these advantages were confirmed in the validation cohort. CONCLUSIONS: The
      present RFS nomogram for AFP-negative HCC patients after curative resection
      provides an accurate and reliable prognostic model to facilitate recurrence
      surveillance. Once AFP-negative patients are predicted to have a high recurrence
      score, additional high-end imaging examinations, such as MRI or CT exams, should
      be considered, and the interval time of regular folow-up should be reduced.

PMID- 29572834
TI  - Impact of BRCA mutations on outcomes among patients with serous endometrial
      cancer.
AB  - OBJECTIVE: To compare the outcome of patients with uterine papillary serous
      cancer (UPSC) carrying a BRCA mutation with that of patients with UPSC who are
      BRCA wild-type. METHODS: The present retrospective, multicenter cohort study
      included women with UPSC who were diagnosed between January 1, 1993, and December
      31, 2014, and were tested for the BRCA mutation at three Israeli medical centers.
      Data were collected from the medical records, and patient and tumor
      characteristics and disease outcomes were compared between BRCA mutation carriers
      and noncarriers. The primary outcome was overall survival. RESULTS: In total, 14
      BRCA mutation carriers and 50 noncarriers were included. Both groups had similar
      treatment modalities (P=0.530). A non-significant trend toward BRCA mutation
      carriers being diagnosed more frequently at an advanced stage compared with
      noncarriers was observed (P=0.090). Median overall survival (25 vs 37 months;
      P=0.442), progression-free survival (37 vs 29 months; P=0.536), and disease
      specific survival (60 vs 39 months; P=0.316) were similar between the carrier and
      noncarrier groups. CONCLUSIONS: Although not significant, BRCA mutation carriers
      tended to have more advanced disease at diagnosis. However, the survival was
      similar irrespective of the BRCA status in this small group. Further research is
      needed to confirm these findings in a larger cohort.

PMID- 29572836
TI  - Letter to the editor: RE: Risk of periodontal disease in patients with asthma: A
      nationwide population-based retrospective cohort study.

PMID- 29572835
TI  - What happens to the pleural space affected by malignant effusion after bedside
      pleurodesis?
AB  - BACKGROUND AND OBJECTIVES: Evaluate radiological characteristics of
      postpleurodesis pleural space of patients with recurrent malignant pleural
      effusion(RMPE). METHODS: Prospective cohort study including patients with RPME
      treated with bedside pleurodesis. We used CT scans to calculate pleural cavity
      volume immediately before pleurodesis(iCT) and 30 days after(CT30). Radiological
      evolution was calculated by the difference between pleural volumes on CT30 and
      iCT(Deltavolume). We categorized initial pleural volume as small(<500 mL) or
      large space(>=500 mL) and Deltavolume as positive(>254.49 mL), unchanged(>=
      268.77-<= 254.49 mL), or negative(<-268.77 mL). Futhermore, we analyzed clinical
      effectiveness, pleural elastance, and adverse events. RESULTS: A total of 87
      patients were analyzed. Pleural volume varied from 35-2750 mL in iCT and from 0
      2995 mL in CT30(P = 0.753). A total of 54 patients had initial small pleural
      space(62.06%) and 33 large(37.93%). Clinical failure occurred in 7.4% of small
      space group and in 24.6% of large(P = 0.051, OR4.0(CI:1.098-14.570)). In small
      space group, 27.77% evolved with positive, 66.66% with unchanged and 5.55% with
      negative Deltavolume. In the large space group these numbers were respectively
      21.21%, 27.27%, and 51.51%. CONCLUSIONS: There is significant variability on
      pleural space volume. However, pleural volume remains unchanged in many cases.
      Besides that, more than half patients with initial large space coursed with
      relevant reduction. Finally, patients with initial small space presented a
      greater chance of clinical success.

PMID- 29572838
TI  - Efficacy of prophylactic probiotics in combination with antibiotics versus
      antibiotics alone for colorectal surgery: A meta-analysis of randomized
      controlled trials.
AB  - This meta-analysis aimed to determine whether prophylactic probiotics in
      combination with antibiotics are superior to antibiotics alone in the prevention
      of surgical site infection (SSI) after colorectal surgery. Fourteen trials
      involving 1524 participants were included. Compared with antibiotics alone,
      prophylactic probiotics in combination with antibiotics reduced the risk of SSI
      as well as other complications, shortened the cumulative duration of antibiotic
      therapy. Current evidence suggested that probiotics in combination with
      antibiotics could be recommended.

PMID- 29572839
TI  - Alcohol intake and periodontitis in adults aged >=30 years: NHANES 2009-2012.
AB  - BACKGROUND: Whether an association between alcohol consumption and periodontitis
      exists is still unclear. This study aimed to assess the association between
      alcohol consumption and periodontitis. METHODS: 7062 adults 30 years or older who
      participated in 2009-2010 and 2011-2012 cycles of the National Health and
      Nutrition Examination Survey (NHANES) were included. Alcohol consumption
      measurement included self-reported average number of alcoholic drinks per week
      over the previous 12 months and was categorized into four groups (0, < 1, 1- < 8,
      and >=8 drinks per week). Participants were categorized using surveillance case
      definitions for periodontitis that included both clinical attachment level (CAL)
      and periodontal probing depth (PD) measurements. The association between alcohol
      consumption and chronic periodontitis was evaluated by multivariable regression
      analyses adjusting for age, gender, race/ethnicity, education level, income-to
      poverty ratio, smoking, self-rated overall oral health, and HbA1c . RESULTS: The
      odds ratio (95% confidence interval) of having severe periodontitis was 1.9 (1.2
      3) among participants who reported alcohol consumption of >=8 drinks compared to
      participants consuming some alcohol but < 1 drink per week on average.
      Participants who consumed 1- < 8, and >=8 drinks per week, on average, also had
      higher mean PD, percentage of sites with PD >=4 mm, mean CAL, and percentage of
      sites with CAL >=3 mm compared to participants reporting consumption of < 1 drink
      per week. Meanwhile, the odds of having periodontitis, mean PD, extent PD >=4 mm,
      mean CAL, and extent CAL >=3 mm were not significantly different for nondrinkers
      than for participants who consumed some alcohol but < 1 drink per week on
      average. CONCLUSIONS: Alcohol consumption was associated with an increase in the
      likelihood of having periodontitis, particularly severe periodontitis.
      Consumption of some alcohol, < 1 drink per week on average, was associated with
      similar odds of having periodontitis compared to consumption of no alcohol.

PMID- 29572837
TI  - Cholecystokinin selectively activates short axon cells to enhance inhibition of
      olfactory bulb output neurons.
AB  - KEY POINTS: Cholecystokinin (CCK) via CCK-B receptors significantly enhances the
      GABAA receptor-mediated synaptic inhibition of principal olfactory bulb (OB)
      output neurons. This CCK action requires action potentials in presynaptic
      neurons. The enhanced inhibition of OB output neurons is a result of CCK-elevated
      inhibitory input from the glomerular circuit. CCK modulation of the glomerular
      circuit also leads to potentiated presynaptic inhibition of olfactory nerve
      terminals and postsynaptic inhibition of glomerular neurons. Selective excitation
      of short axon cells underlies the CCK-potentiated glomerular inhibition.
      ABSTRACT: Neuropeptides such as cholecystokinin (CCK) are important for many
      brain functions, including sensory processing. CCK is predominantly present in a
      subpopulation of excitatory neurons and activation of CCK receptors is implicated
      in olfactory signal processing in the olfactory bulb (OB). However, the cellular
      and circuit mechanisms underlying the actions of CCK in the OB remain elusive. In
      the present study, we characterized the effects of CCK on synaptic inhibition of
      the principal OB output neurons mitral/tufted cells (MTCs) followed by
      mechanistic analyses at both circuit and cellular levels. First, we found that
      CCK via CCK-B receptors enhances the GABAA receptor-mediated spontaneous IPSCs in
      MTCs. Second, CCK does not affect the action potential independent miniature
      IPSCs in MTCs. Third, CCK potentiates glomerular inhibition resulting in
      increased GABAB receptor-mediated presynaptic inhibition of olfactory nerve
      terminals and enhanced spontaneous IPSCs in MTCs and glomerular neurons. Fourth,
      CCK enhances miniature IPSCs in the excitatory external tufted cells, although
      neither in the inhibitory short axon cells (SACs) nor in periglomerular cells
      (PGCs). Finally, CCK excites all tested SACs and a very small minority of
      GABAergic neurons in the granule cell layer or in periglomerular cells, but not
      in deep SACs. These results demonstrate that CCK selectively activates SACs to
      engage the SAC-formed interglomerular circuit and thus elevates inhibition
      broadly in the OB glomerular layer. This modulation may prevent the system from
      saturating in response to a high concentration of odourants or facilitate the
      detection of weak stimuli by increasing signal-to-noise ratio.

PMID- 29572840
TI  - Reply from authors: RE: Risk of periodontal disease in patients with asthma: A
      nationwide population-based retrospective cohort study.

PMID- 29572841
TI  - Spinal associative plasticity in depth: evidence from animal model.

PMID- 29572842
TI  - Sucrose transport and carbon fluxes during wood formation.
AB  - Wood biosynthesis defines the chemical and structural properties of wood. The
      metabolic pathways that produce the precursors of wood cell wall polymers have a
      central role in defining wood properties. To make rational design of wood
      properties feasible, we need not only to understand the cell wall biosynthetic
      machinery, but also how sucrose transport and metabolism in developing wood
      connect to cell wall biosynthesis and how they respond to genetic and
      environmental cues. Here, we review the current understanding of the sucrose
      transport and primary metabolism pathways leading to the precursors of cell wall
      biosynthesis in woody plant tissues. We present both old, persistent questions
      and new emerging themes with a focus on wood formation in trees and draw upon
      evidence from the xylem tissues of herbaceous plants when it is relevant.

PMID- 29572844
TI  - Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of
      oxidative stress, inflammation and extracellular matrix remodeling.
AB  - Diabetic peripheral neuropathy is one of the most common microvascular
      complications that occurs with both type 1 and type 2 diabetes mellitus. It has a
      significant negative impact on patients' quality of life; as it starts with loss
      of limbs' sensation and may lead to lower limb amputation. This study aimed at
      investigating the effect of liraglutide on peripheral neuropathy in diabetic
      rats. Experimental diabetes was induced by single intraperitoneal injections of
      nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were allocated into
      five groups. Two groups were given saline or liraglutide (0.8 mg/kg, s.c.). Three
      diabetic groups were either untreated or treated with liraglutide (0.8 mg/kg,
      s.c.) or pregabalin (10 mg/kg, i.p.). After 2 weeks of treatment, behavioral,
      biochemical, histopathological, and immunohistochemical investigations were
      performed. Treatment with liraglutide-restored animals' body weight, normalized
      blood glucose, decreased glycated hemoglobin, and increased insulin levels. In
      parallel, it normalized motor coordination and the latency withdrawal time of
      both tail flick and hind paw cold allodynia tests and reversed histopathological
      alterations. Treatment with liraglutide also normalized malondialdehyde, matrix
      metalloproteinase-2 and -9 contents in sciatic nerve. Likewise, it decreased
      sciatic nerve nitric oxide and interleukin-6 contents, DNA fragmentation and
      expression of cyclooxygenase-2. Meanwhile, it increased superoxide dismutase and
      interleukin-10 contents in sciatic nerve. These findings indicate the
      neuroprotective effect of liraglutide against diabetic peripheral neuropathy
      probably via modulating oxidative stress, inflammation, and extracellular matrix
      remodeling.

PMID- 29572843
TI  - A retrospective investigation of hexavalent chromium allergy in southern Sweden.
AB  - BACKGROUND: Historically, allergic contact dermatitis caused by hexavalent
      chromium [Cr(VI)] in cement was the most common cause of invalidity attributable
      to skin disease in Sweden. Since the legislation to reduce Cr(VI) in cement was
      introduced in 1989, we rarely see allergic contact dermatitis caused by cement.
      OBJECTIVES: To examine the frequency of contact allergy to Cr(VI) in southern
      Sweden in 2005-2014. METHODS: We investigated the occurrence of positive
      reactions to potassium dichromate 0.5% pet. in consecutively tested dermatitis
      patients, and compared the occurrence of atopic dermatitis, localization of
      dermatitis and simultaneous positive reactions to cobalt chloride and nickel
      sulfate in the Cr(VI)-positive patients with those in a group of patients with a
      similar age and sex distribution. RESULTS: In total, 6482 patients were tested,
      and 233 Cr(VI)-allergic individuals were found (3.6%). A significantly higher
      proportion of atopic dermatitis was found among Cr(VI)-allergic patients, and a
      significantly higher share of foot dermatitis was found among Cr(VI)-allergic
      women, than among controls. Cr(VI) allergy was less likely when both nickel
      allergy and cobalt allergy were present. CONCLUSION: A relatively high frequency
      of contact allergy to Cr(VI) was found. The cause has shifted from cement
      exposure to other exposures, probably mainly leather.

PMID- 29572845
TI  - Magnesium promotes root nodulation through facilitation of carbohydrate
      allocation in soybean.
AB  - Magnesium (Mg) is an essential element for the growth of both plants and
      bacteria. Low availability of Mg in agriculture can limit crop productivity and
      quality. In addition to direct effects on plant growth, limited Mg supply may
      also impact biological dinitrogen (N2 ) fixation in nodules formed from symbiotic
      interactions between legumes and rhizobial bacteria. To date, the physiological
      mechanisms involved in Mg-dependent nodulation remains largely unknown. The
      objectives of this work were to assess how Mg supply affects nodule growth and
      development in symbiotic systems, and to test if any observed changes in nodule
      and soybean are correlated with Mg supply. Here, we found that external Mg supply
      enhanced nodule growth under nitrogen (N) limited conditions, and subsequently
      improved N2 fixation and soybean growth. Mg supply altered neither nodule
      structure nor Mg homeostasis, but remarkably promoted nodule enlargement,
      resulting in an increase in the number of big nodules. In addition, high Mg
      supply decreased starch and sucrose accumulation in leaves, and increased their
      concentrations in roots, which consequently enhanced carbohydrate import into the
      rhizobia infection zone of nodules. In this study, Mg was shown to promote nodule
      growth in soybean. This Mg-promoted nodule growth is derived from Mg-facilitated
      alteration of carbohydrate partitioning and transport into nodules.

PMID- 29572846
TI  - Occupational allergic contact dermatitis caused by Acticide MV, a brand name for
      the mixture methylchloroisothiazolinone/methylisothiazolinone.

PMID- 29572847
TI  - Sedative-hypnotic and anxiolytic effects and the mechanism of action of aqueous
      extracts of peanut stems and leaves in mice.
AB  - INTRODUCTION: Peanut stems and leaves (PSL) have traditionally been used as both
      a special food and a herbal medicine in Asia. The sedative-hypnotic and
      anxiolytic effects of PSL have been recorded in classical traditional Chinese
      literature, and more recently by many other researchers. In a previous study,
      four sleep-related ingredients (linalool, 5-hydroxy-4',7-dimethoxyflavanone, 2'-O
      methylisoliquiritigenin and ferulic acid), among which 5-hydroxy-4',7
      dimethoxyflavanone and 2'-O-methylisoliquiritigenin were newly found in Arachis
      species, were screened by ultrahigh-performance liquid chromatography coupled
      with quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). In the current
      study, quantitative examination of the above four ingredients was conducted.
      Serious fundamental functional studies were done in mice, including locomotor
      activity, direct sleep tests, pentobarbital-induced sleeping time tests,
      subthreshold dose of pentobarbital tests and barbital sodium sleep incubation
      period tests, to determine the material base for the sedative-hypnotic and
      anxiolytic effects of aqueous extracts of PSL. Furthermore, neurotransmitter
      levels in three brain regions (cerebrum, cerebellum and brain stem) were
      determined using UHPLC coupled with triple-quadrupole mass spectrometry
      (UHPLC/QQQ-MS) in order to elucidate the exact mechanism of action. RESULTS:
      Aqueous extract of PSL at a dose of 500 mg kg-1 (based on previous experience),
      along with different concentrations of the above four functional ingredients
      (189.86 ug kg-1 linalool, 114.75 mg kg-1 5-hydroxy-4',7-dimethoxyflavanone,
      32.4mg kg-1 2'-O-methylisoliquiritigenin and 44.44 mg kg-1 ferulic acid), had a
      sedative-hypnotic effect by affecting neurotransmitter levels in mice.
      CONCLUSION: The data demonstrate that these four ingredients are the key
      functional factors for the sedative-hypnotic and anxiolytic effects of PSL
      aqueous extracts and that these effects occur via changes in neurotransmitter
      levels and pathways. (c) 2018 Society of Chemical Industry.

PMID- 29572848
TI  - Experimental validation of absolute SPECT/CT quantification for response
      monitoring in breast cancer.
AB  - PURPOSE: Recent developments in iterative image reconstruction enable absolute
      quantification of SPECT/CT studies by incorporating compensation for collimator
      detector response, attenuation, and scatter as well as resolution recovery into
      the reconstruction process (Evolution; Q.Metrix package; GE Healthcare, Little
      Chalfont, UK). The aim of this experimental study is to assess its quantitative
      accuracy for potential clinical 99m Tc-sestamibi (MIBI)-related SPECT/CT
      application in neoadjuvant chemotherapy response studies in breast cancer.
      METHODS: Two phantoms were filled with MIBI and acquired on a SPECT/CT gamma
      camera (Discovery 670 Pro; GE Healthcare), that is, a water cylinder and a NEMA
      body phantom containing six spheres that were filled with an activity
      concentration reflecting clinical MIBI uptake. Subsequently, volumes-of-interest
      (VOI) of each sphere were drawn (semi)automatically on SPECT using various
      isocontour methods or manually on CT. Finally, prone MIBI SPECT/CT scans were
      acquired 5 and 90 min p.i. in a locally advanced breast cancer patient. RESULTS:
      Activity concentration in the four largest spheres converged after nine
      iterations of evolution. Depending on the count statistics, the accuracy of the
      reconstructed activity concentration varied between -4.7 and -0.16% (VOI covering
      the entire phantom) and from 6.9% to 10% (8.8 cm ? cylinder VOI placed in the
      center of the phantom). Recovery coefficients of SUVmax were 1.89 +/- 0.18, 1.76
      +/- 0.17, 2.00 +/- 0.38, 1.89 +/- 0.35, and 0.90 +/- 0.26 for spheres with 37,
      28, 22, 17, and 13 mm ?, respectively. Recovery coefficients of SUVmean were 1.07
      +/- 0.06, 1.03 +/- 0.09, 1.17 +/- 0.21, 1.10 +/- 0.20, and 0.52 +/- 0.14 (42%
      isocontour); 1.10 +/- 0.07, 1.02 +/- 0.09, 1.13 +/- 0.19, 1.06 +/- 0.19, and 0.51
      +/- 0.13 (36% isocontour with local background correction); and 0.96, 1.09, 1.03,
      1.03, and 0.29 (CT). Patient study results were concordant with the phantom
      validation. CONCLUSIONS: Absolute SPECT/CT quantification of breast studies using
      MIBI seems feasible (<17% deviation) when a 42% isocontour is used for
      delineation for tumors of at least 17 mm diameter. However, with tumor shrinkage,
      response evaluation should be handled with caution, especially when using SUVmax
      .

PMID- 29572849
TI  - The role of C2H2 zinc finger proteins in plant responses to abiotic stresses.
AB  - Abiotic stresses are important factors affecting plant growth and development and
      limiting agricultural production worldwide. Plants have evolved complex
      regulatory mechanisms to respond and adapt to constantly changing environmental
      conditions. C2H2 zinc finger proteins form a relatively large family of
      transcriptional regulators in plants. Recent studies have revealed that C2H2 zinc
      finger proteins function as key transcriptional regulators in plant responses to
      a wide spectrum of stress conditions, including extreme temperatures, salinity,
      drought, oxidative stress, excessive light and silique shattering. Here, we
      summarize recent functional analysis on C2H2 zinc finger proteins in plant
      responses to abiotic stresses and discuss their roles as part of a large
      regulatory network in the perception and responses by plants to different
      environmental stimuli.

PMID- 29572850
TI  - Ethnic differences in the association between maternal vitamin D status and
      offspring asthma and wheeze: Findings from the Born in Bradford cohort study.

PMID- 29572851
TI  - Mortality and Functional Outcomes After Minor Urological Surgery in Nursing Home
      Residents: A National Study.
AB  - OBJECTIVES: To determine outcomes of minor urological surgery in frail older
      adults. DESIGN: Retrospective cohort study. SETTING: U.S. nursing homes (NHs).
      PARTICIPANTS: NH residents aged 65 and older undergoing minor inpatient
      urological surgery (cystoscopy, bladder biopsy, transurethral resection of
      bladder tumor, prostate biopsy, transurethral resection of prostate, removal of
      ureteral obstruction, suprapubic tube placement) in the United States between
      2004 and 2012 (N=34,605). MEASUREMENTS: One-year mortality and changes in
      functional status before and after surgery using the Minimum Data Set Activity of
      Daily Living (MDS-ADL) summary scale. RESULTS: Overall 1-year mortality was 50%,
      and on average, residents had a 1.9-point worsening in their MDS-ADL score at 1
      year, whereas the most highly functional residents (baseline quartile of MDS-ADL
      scores (0-12)) had a 4.7-point worsening in their MDS-ADL scores at 1 year.
      Functional decline in residents 1 year after surgery was associated with decline
      in function in the 6 months before surgery (adjusted hazard ratio (aH)=2.39, 95%
      confidence interval (CI)=2.29-2.49), emergency procedures (aHR=1.37, 95% CI=1.31
      1.43), older age (>=85 vs 65-74, aHR=1.17, 95% CI=1.11-1.23), and baseline
      cognitive impairment (aHR=1.15, 95% CI=1.11-1.20). CONCLUSION: Despite the low
      complexity of minor urological procedures, NH residents experience high mortality
      and many demonstrate sustained functional decline up to 1-year postoperatively.

PMID- 29572852
TI  - Detecting violation in abstract pitch patterns with mismatch negativity.
AB  - The human brain automatically extracts regularities embedded in environmental
      auditory events. This study investigated the extraction of abstract patterns by
      measuring mismatch negativity (MMN). Participants watched a silent subtitled
      movie and ignored a sequence of auditory events comprising frequent standards and
      rare deviants presented in the background. Tone triplets with varying pitch
      (first-order property) served as the auditory events. The pitch intervals
      (interval 1 and interval 2) between the tones in a triplet and the ratio of
      interval 1 and 2 were considered second- and third-order properties,
      respectively. Both second- and third-order properties of the standards were kept
      constant in the mixed patterns block, while only the third-order property was
      kept constant in the ratio pattern block. Four sets of tone triplets violating
      the interval and ratio patterns with different deviance levels were presented as
      deviants in both blocks, and subtracted with physically identical stimuli in a
      control block to isolate the MMNs. Interval and ratio pattern deviants elicited
      MMNs in the mixed patterns block while only ratio pattern deviants elicited MMNs
      in the ratio pattern block. Larger MMNs were elicited by large deviants as
      compared to small deviants. These results suggest that the change detection
      system is sensitive to the violation of both second- and third-order abstract
      patterns. In addition to regularities in the abstract properties of auditory
      events, regularities in the relationships between abstract properties can also be
      extracted. This ability plays an important role in music and language perception.

PMID- 29572853
TI  - Plant and algal structure: from cell walls to biomechanical function.
AB  - Plant and algal cell walls are complex biomaterials composed of stiff cellulose
      microfibrils embedded in a soft matrix of polysaccharides, proteins and phenolic
      compounds. Cell wall composition differs between taxonomic groups and different
      tissue types (or even at the sub-cellular level) within a plant enabling specific
      biomechanical properties important for cell/tissue function. Moreover, cell wall
      composition changes may be induced in response to environmental conditions. Plant
      structure, habit, morphology and internal anatomy are also dependent on the
      taxonomic group as well as abiotic and biotic factors. This review aims to
      examine the complex and incompletely understood interactions of cell wall
      composition, plant form and biomechanical function.

PMID- 29572854
TI  - Acute generalized exanthematous pustulosis caused by ibuprofen-Diagnosis
      confirmed by patch testing.

PMID- 29572855
TI  - Airborne dermatitis in a child caused by isothiazolinones in a water-based paint
      in Italy: Call for better regulations.

PMID- 29572856
TI  - The relative biological effectiveness for carbon, nitrogen, and oxygen ion beams
      using passive and scanning techniques evaluated with fully 3D silicon
      microdosimeters.
AB  - BACKGROUND: The aim of this study was to measure the microdosimetric
      distributions of a carbon pencil beam scanning (PBS) and passive scattering
      system as well as to evaluate the relative biological effectiveness (RBE) of
      different ions, namely 12 C, 14 N, and 16 O, using a silicon-on-insulator (SOI)
      microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations
      were performed with the same experimental setup and results were compared to the
      experimental results for benchmarking. METHOD: Two different silicon
      microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both
      10 MUm in thickness were used in this study. The microdosimeters were connected
      to low noise electronics which allowed for the detection of lineal energies as
      low as 0.15 keV/MUm in tissue. The silicon microdosimeters provide extremely high
      spatial resolution and can be used for in-field and out-of-field measurements in
      both passive scattering and PBS deliveries. The response of the microdosimeters
      was studied in 290 MeV/u 12 C, 180 MeV/u 14 N, 400 MeV/u 16 O passive ion beams,
      and 290 MeV/u 12 C scanning carbon therapy beam at heavy ion medical accelerator
      in Chiba (HIMAC) and Gunma University Heavy Ion Medical Center (GHMC), Japan,
      respectively. The microdosimeters were placed at various depths in a water
      phantom along the central axis of the ion beam, and at the distal part of the
      Spread Out Bragg Peak (SOBP) in 0.5 mm increments. The RBE values of the pristine
      Bragg peak (BP) and SOBP were derived using the microdosimetric lineal energy
      spectra and the modified microdosimetric kinetic model (MKM), using MKM input
      parameters corresponding to human salivary gland (HSG) tumor cells. Geant4
      simulations were performed in order to verify the calculated depth-dose
      distribution from the treatment planning system (TPS) and to compare the
      simulated dose-mean lineal energy to the experimental results. RESULTS: For a 180
      MeV/u 14 N pristine BP, the dose-mean lineal energy yD- obtained with two types
      of silicon microdosimeters started from approximately 29 keV/MUm at the entrance
      to 92 keV/MUm at the BP, with a maximum value in the range of 412 to 438 keV/MUm
      at the distal edge. For 400 MeV/u 16 O ions, the dose-mean lineal energy yD-
      started from about 24 keV/MUm at the entrance to 106 keV/MUm at the BP, with a
      maximum value of approximately 381 keV/MUm at the distal edge. The maximum
      derived RBE10 values for 14 N and 16 O ions were found to be 3.10 +/- 0.47 and
      2.93 +/- 0.45, respectively. Silicon microdosimetry measurements using pencilbeam
      scanning 12 C ions were also compared to the passive scattering beam.
      CONCLUSIONS: These SOI microdosimeters with well-defined three-dimensional (3D)
      SVs have applicability in characterizing heavy ion radiation fields and measuring
      lineal energy deposition with sub-millimeter spatial resolution. It has been
      shown that the dose-mean lineal energy increased significantly at the distal part
      of the BP and SOBP due to very high LET particles. Good agreement was observed
      for the experimental and simulation results obtained with silicon microdosimeters
      in 14 N and 16 O ion beams, confirming the potential application of SOI
      microdosimeter with 3D SV for quality assurance in charged particle therapy.

PMID- 29572857
TI  - Comparison of reactivity to a metallic disc and 2% aluminium salt in 366
      children, and reproducibility over time for 241 young adults with childhood
      vaccine-related aluminium contact allergy.
AB  - BACKGROUND: An aluminium hydroxide-adsorbed pertussis toxoid vaccine was studied
      in 76 000 children in the 1990s in Gothenburg, Sweden. Long-lasting itchy
      subcutaneous nodules at the vaccination site were seen in 745 participants. Of
      495 children with itchy nodules who were patch tested for aluminium allergy, 377
      were positive. In 2007-2008, 241 of the positive children were retested. Only in
      one third were earlier positive results reproduced. OBJECTIVES: To further
      describe patch test reactions to different aluminium compounds in children with
      vaccine-induced aluminium allergy. PATIENTS/METHODS: Positive patch test results
      for metallic aluminium (empty Finn Chamber) and aluminium chloride hexahydrate 2%
      petrolatum (pet.) were analysed in 366 children with vaccine-induced persistent
      itching nodules tested in 1998-2002. Of those, 241 were tested a second time
      (2007-2008), and the patch test results of the two aluminium preparations were
      analysed. RESULTS: Patch testing with aluminium chloride hexahydrate 2% pet. is a
      more sensitive way to diagnose aluminium contact allergy than patch testing with
      metallic aluminium. A general decrease in the strength of reactions to both
      aluminium preparations in 241 children tested twice was observed. CONCLUSIONS:
      Aluminium contact allergy can be diagnosed by patch testing without using
      metallic aluminium.

PMID- 29572858
TI  - Red blood cell transfusion in perioperative pediatric anesthesia: a survey of
      current practice in Germany.
AB  - BACKGROUND: Little is known about the current practice of the perioperative
      transfusion of red blood cells (RBCs) in pediatric patients. This study was
      performed to evaluate the practice of RBC transfusion in German pediatric
      anesthesia. STUDY DESIGN AND METHODS: An online survey was conducted among
      members of the German Society of Anesthesiology and Intensive Care. Participants
      were asked to indicate the hemoglobin (Hb) thresholds for starting RBC
      transfusion in six cases of different bleeding situations in pediatric
      anesthesia. Demographics of participants, general knowledge, and application of
      transfusion rules and guidelines were assessed. RESULTS: We included 1207 of 1396
      returned questionnaires. Of the respondents, 89% were qualified specialists and
      68% had experience in anesthesia in children aged less than 6 months. The lowest
      median Hb transfusion threshold was 6 g/dL in a 16-year-old and the highest was
      10 g/dL in a premature neonate. Intraoperative Hb thresholds increased for
      clinically unstable (median difference to clinically stable children, +1 g/dL; p
      < 0.001) or neonate and premature children (median difference to older children,
      +1 and +2 g/dL; p < 0.001). The stated Hb threshold ranges were broad, especially
      in neonates or premature children (interquartile range, neonates 3, premature
      children 4 g/dL). Of the participants, only 16% had knowledge of a guideline that
      includes blood transfusion in children. CONCLUSION: Striking variability exists
      in practice of perioperative pediatric RBC transfusion. A specialized guideline
      for perioperative blood transfusion in children could be helpful to define and
      promote optimal pediatric RBC transfusion strategies.

PMID- 29572859
TI  - Blood donors' preferences for blood donation for biomedical research.
AB  - BACKGROUND: Increasing numbers of blood donors are recruited to participate in
      biomedical research. As blood services depend on voluntary donors, successful
      recruitment calls for a better understanding of donors' expectations and
      attitudes toward the use of samples in research. STUDY DESIGN AND METHODS: Sixty
      one semistructured interviews were conducted with blood donors at eight Finnish
      Red Cross Blood Service donation sites in Finland. The 10- to 30-minute
      interviews included open-ended questions about donors' views on blood donation
      for patients and for biomedical research. Central motives to donate blood for
      patients were identified against which views on research use were compared to see
      how these reflections differed. RESULTS: Six central motives for donating blood
      for patients were identified among donors. The interviewees were, in general,
      willing to donate blood for research, but considered research donation more
      likely if it could be easily integrated into their usual blood donation habits.
      Biomedical research was perceived as important but its social benefits were more
      abstract than a direct help to patients. CONCLUSIONS: Familiarity and reciprocity
      were key to the relationship between the blood service and blood donors. Donation
      for research introduces a new, more complex context to blood donation. Challenge
      to recognize concrete outcomes and benefits of donation may affect willingness to
      donate for research. Transparent communication of the role of the blood service
      in research and of the beneficiaries of the research is essential in maintaining
      trust. These results will help blood services in their planning to recruit blood
      donors for research projects.

PMID- 29572860
TI  - Organic iodine supply affects tomato plants differently than inorganic iodine.
AB  - Iodine is a beneficial element for humans but very lowly represented in our diet.
      Iodine-enriched vegetables could boost the iodine content in the food chain.
      Despite being a beneficial element for plants, little is known about the effect
      of different iodine forms on plant growth. This work analyses the effect of
      uptake of mineral (KI) and organoiodine (5-iodosalicylic acid, 5-ISA; 3,5
      diiodosalicylic acid, 3,5-di-ISA; 2-iodobenzoic acid, 2-IBeA; 4-iodobenzoic acid,
      4-IBeA) compounds on tomato plants at an early stage of vegetative growth. As
      many organoiodine compounds are derived from salicylic (SA) and benzoic acids
      (BeA), treatments with I, SA and BeA in various treatments were realized and the
      influence of tested compounds on plant growth was analyzed. Iodine content was
      measured, as well as expression of key genes involved in I and SA metabolism.
      Organoiodine compounds accumulated mainly in roots whereas iodine accumulated in
      the upper parts when given as KI. The shoot system had 5, 12 and 25 times higher
      iodine content after KI treatment than after 4-IBeA, 5-ISA and 2-IBeA, or 3,5
      diISA treatments, respectively. A toxic effect on plants was observed only for
      3,5-diISA and 4-IBeA. The expression levels of a gene related to iodine
      metabolism (HMT, halide ion methylotransferase), a gene responsible for SA
      methylation in leaves (SAMT) and a gene related to SA catabolism (S3H, salicylic
      acid 3-hydroxylase) were modified differently depending on the iodine source.
      Overall, our data point out to a difference in plant uptake, transport of iodine
      in tomato plants based on the form of iodine compound.

PMID- 29572861
TI  - Expression of tenascin-C in a rat vocal fold injury model and its regulation of
      fibroblasts.
AB  - OBJECTIVES/HYPOTHESIS: Tenascin-C (Tnc) is an extracellular matrix (ECM)
      glycoprotein that plays a vital role in wound healing and fibrotic disease. Tnc
      is highly upregulated soon after vocal fold injury, but its function in the vocal
      fold has not yet been defined. In this study, we investigated Tnc expression in a
      rat vocal fold injury model in vivo and its roles in fibroblasts in vitro. STUDY
      DESIGN: In vivo and in vitro. METHODS: Tnc mRNA and protein expression levels
      were quantified on days 3, 7, 14, 28, and 56 after vocal fold injury in Sprague
      Dawley rats. In vitro, immunocytochemistry, Western blot, and quantitative real
      time polymerase chain reaction (qRT-PCR) analyses were performed in primary rat
      vocal fold fibroblasts following Tnc or transforming growth factor (TGF)-beta1
      stimulation to investigate the phenotypic effects. RESULTS: Tnc mRNA and protein
      expression was upregulated dramatically on days 3 and 7 after injury, and
      significant differences were observed by qRT-PCR (P < .01). In vitro, Tnc
      significantly stimulated the migration of primary vocal fold fibroblasts.
      Following incubation with Tnc for 72 hours, alpha-smooth muscle actin, collagen
      I, and fibronectin expression was significantly upregulated (P < .05). TGF-beta1
      increased Tnc expression in a time-dependent manner, and a mothers against
      decapentaplegic homolog 3 (SMAD3) inhibitor attenuated this TGF-beta1-induced
      stimulation. CONCLUSIONS: Tnc was highly upregulated during the early postinjury
      period in vivo and promoted vocal fold fibroblast migration,
      transdifferentiation, and ECM protein synthesis in vitro. Tnc was induced by TGF
      beta1 in a SMAD3-dependent manner. Transient expression of Tnc is likely to
      promote regeneration, but its potential role in fibrosis requires further study.
      LEVEL OF EVIDENCE: NA Laryngoscope, 128:E316-E322, 2018.

PMID- 29572863
TI  - Enantioselective capillary electrophoresis provides insight into the phase II
      metabolism of ketamine and its metabolites in vivo and in vitro.
AB  - Glucuronidation catalyzed by uridine-5'-diphospho-glucuronosyl-transferases
      (UGTs) is the most important reaction in phase II metabolism of drugs and other
      compounds. O-glucuronidation is more common than N-glucuronidation. The
      anesthetic, analgesic and antidepressive drug ketamine is metabolized in phase I
      by cytochrome P450 enzymes to norketamine, hydroxynorketamine (HNK) diastereomers
      and dehydronorketamine (DHNK). Equine urine samples collected two hours after
      ketamine injection were treated with beta-glucuronidase and analyzed with three
      enantioselective capillary electrophoresis assays. Concentrations of HNK
      diastereomers and norketamine were significantly higher in comparison to
      untreated urine and an increase of ketamine and DHNK levels was found in selected
      but not all samples. This suggests that O-glucuronides of HNK and N-glucuronides
      of the other compounds are formed in equines. N-glucuronidation of norketamine
      was studied in vitro with liver microsomes of different species and the single
      human enzyme UGT1A4. With equine liver microsomes (ELM) a stereoselective N
      glucuronidation of norketamine was found that compares well to the results
      obtained with urines collected after ketamine administration. No reaction was
      observed with canine liver microsomes, human liver microsomes and UGT1A4.
      Incubation of ketamine and DHNK with ELM did not reveal any glucuronidation.
      Enantioselective CE is suitable to provide insight into the phase II metabolism
      of ketamine and its metabolites.

PMID- 29572862
TI  - Detection, characterization, and enrollment of donors of Ebola convalescent
      plasma in Sierra Leone.
AB  - BACKGROUND: Passive therapy with convalescent plasma provides an early
      opportunity to intervene in Ebola virus disease (EVD). Methods for field
      screening and selection of potential donors and quantifying plasma antibody are
      needed. STUDY DESIGN AND METHODS: Recombinant Ebola virus glycoprotein (EBOV GP)
      was formatted into immunoglobulin G-capture, competitive, and double-antigen
      bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone,
      were recruited as potential plasma donors and assessed locally using sera alone
      and/or paired sera and oral fluids (ORFs). Uninfected controls comprised
      unexposed Gambians and communities in Western Area, Sierra Leone. Antibody
      neutralization in selected sera was measured retrospectively in a pseudotype
      virus assay. RESULTS: A total of 115 potential donors were considered for
      enrollment: 110 plasma samples were concordantly reactive in the three EIAs;
      three were concordantly unreactive and two were reactive in two of three EIAs
      (98.2% agreement; 95% confidence interval [CI], 93.9%-99.8%). In 88 donors with
      paired ORF and plasma, G-capture EIA reactivity correlated well in the two
      analytes (R2  = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF
      samples from 338 of 339 unexposed Western Area community controls were unreactive
      (specificity, 99.7%; 95% CI, 98.4%-99.7%); ORF samples from 113 of 116 Kerry Town
      EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%-99.5%). Strong
      reactivity in G-capture and/or competitive EIAs identified donors with high
      plasma EBOV GP antibody levels in the double-antigen bridging assay, correlating
      with high levels of neutralizing antibody. CONCLUSIONS: In-field testing can
      qualify convalescent donors for providing high-titer antibody.

PMID- 29572864
TI  - Genome editing in potato via CRISPR-Cas9 ribonucleoprotein delivery.
AB  - Clustered regularly interspaced short palindromic repeats and CRISPR-associated
      protein-9 (CRISPR-Cas9) can be used as an efficient tool for genome editing in
      potato (Solanum tuberosum). From both a scientific and a regulatory perspective,
      it is beneficial if integration of DNA in the potato genome is avoided. We have
      implemented a DNA-free genome editing method, using delivery of CRISPR-Cas9
      ribonucleoproteins (RNPs) to potato protoplasts, by targeting the gene encoding a
      granule bound starch synthase (GBSS, EC 2.4.1.242). The RNP method was directly
      implemented using previously developed protoplast isolation, transfection and
      regeneration protocols without further adjustments. Cas9 protein was preassembled
      with RNA produced either synthetically or by in vitro transcription. RNP with
      synthetically produced RNA (cr-RNP) induced mutations, i.e. indels, at a
      frequency of up to 9%, with all mutated lines being transgene-free. A mutagenesis
      frequency of 25% of all regenerated shoots was found when using RNP with in vitro
      transcriptionally produced RNA (IVT-RNP). However, more than 80% of the shoots
      with confirmed mutations had unintended inserts in the cut site, which was in the
      same range as when using DNA delivery. The inserts originated both from DNA
      template remnants from the in vitro transcription, and from chromosomal potato
      DNA. In 2-3% of the regenerated shoots from the RNP-experiments, mutations were
      induced in all four alleles resulting in a complete knockout of the GBSS enzyme
      function.

PMID- 29572866
TI  - TopoMS: Comprehensive topological exploration for molecular and condensed-matter
      systems.
AB  - We introduce TopoMS, a computational tool enabling detailed topological analysis
      of molecular and condensed-matter systems, including the computation of atomic
      volumes and charges through the quantum theory of atoms in molecules, as well as
      the complete molecular graph. With roots in techniques from computational
      topology, and using a shared-memory parallel approach, TopoMS provides scalable,
      numerically robust, and topologically consistent analysis. TopoMS can be used as
      a command-line tool or with a GUI (graphical user interface), where the latter
      also enables an interactive exploration of the molecular graph. This paper
      presents algorithmic details of TopoMS and compares it with state-of-the-art
      tools: Bader charge analysis v1.0 (Arnaldsson et al., 01/11/17) and molecular
      graph extraction using Critic2 (Otero-de-la-Roza et al., Comput. Phys. Commun.
      2014, 185, 1007). TopoMS not only combines the functionality of these individual
      codes but also demonstrates up to 4* performance gain on a standard laptop,
      faster convergence to fine-grid solution, robustness against lattice bias, and
      topological consistency. TopoMS is released publicly under BSD License. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29572865
TI  - Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to
      outcomes.
AB  - OBJECTIVE: To investigate the clinical and surgical outcome correlates of
      preoperative hippocampal subfield volumes in patients with refractory temporal
      lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence
      segmentation technique. METHODS: We recruited 106 patients with TLE and
      hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI
      inversion recovery MRI. An automated hippocampal segmentation algorithm was used
      to identify twelve subfields in each hippocampus. A total of 76 patients
      underwent amygdalohippocampectomy and postoperative seizure outcome assessment
      using the standardized ILAE classification. Semiquantitative hippocampal internal
      architecture (HIA) ratings were correlated with hippocampal subfield volumes.
      RESULTS: Patients with left TLE had smaller volumes of the contralateral
      presubiculum and hippocampus-amygdala transition area compared to those with
      right TLE. Patients with right TLE had reduced contralateral hippocampal tail
      volumes and improved outcomes. In all patients, there were no significant
      relationships between hippocampal subfield volumes and clinical variables such as
      duration and age at onset of epilepsy. There were no significant differences in
      any hippocampal subfield volumes between patients who were rendered seizure free
      and those with persistent postoperative seizure symptoms. Ipsilateral but not
      contralateral HIA ratings were significantly correlated with gross hippocampal
      and subfield volumes. CONCLUSIONS: Our results suggest that ipsilateral
      hippocampal subfield volumes are not related to the chronicity/severity of TLE.
      We did not find any hippocampal subfield volume or HIA rating differences in
      patients with optimal and unfavorable outcomes. In patients with TLE and HS,
      sophisticated analysis of hippocampal architecture on MRI may have limited value
      for prediction of postoperative outcome.

PMID- 29572867
TI  - Trends over time in congenital malformations in live-born children conceived
      after assisted reproductive technology.
AB  - INTRODUCTION: Children born after assisted reproductive technology, particularly
      singletons, have been shown to have an increased risk of congenital malformations
      compared with children born after spontaneous conception. We wished to study
      whether there has been a change in the past 20 years in the risk of major
      congenital malformations in children conceived after assisted reproductive
      technology compared with children spontaneously conceived. MATERIAL AND METHODS:
      Population-based cohort study including 90 201 assisted reproductive technology
      children and 482 552 children spontaneously conceived, born in Denmark, Finland,
      Norway and Sweden. Both singletons and twins born after in vitro fertilization,
      intracytoplasmatic sperm injection and frozen embryo transfer were included. Data
      on children were taken from when the national Nordic assisted reproductive
      technology registries were established until 2007. Multiple logistic regression
      analyses were used to estimate the risks and adjusted odds ratios for congenital
      malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003
      2007. Only major malformations were included. RESULTS: The absolute risk for
      singletons of being born with a major malformation was 3.4% among assisted
      reproductive technology children vs. 2.9% among children spontaneously conceived
      during the study period. The relative risk of being born with a major congenital
      malformation between all assisted reproductive technology children and children
      spontaneously conceived remained similar through all four time periods (p =
      0.39). However, we found that over time the number of children diagnosed with a
      major malformation increased in both groups across all four time periods.
      CONCLUSION: When comparing children conceived after assisted reproductive
      technology and spontaneously conceived, the relative risk of being born with a
      major congenital malformation did not change during the study period.

PMID- 29572868
TI  - Apigenin inhibits sciatic nerve denervation-induced muscle atrophy.
AB  - INTRODUCTION: Apigenin (AP) has been reported to elicit anti-inflammatory
      effects. In this study, we investigated the effect of AP on sciatic nerve
      denervation-induced muscle atrophy. METHODS: Sciatic nerve-denervated mice were
      fed a 0.1% AP-containing diet for 2 weeks. Muscle weight and cross-sectional area
      (CSA), and the expression of atrophic genes and inflammatory cytokines in the
      gastrocnemius were analyzed. RESULTS: Denervation significantly induced muscle
      atrophy. However, values for muscle weight and CSA were greater in the denervated
      muscle of the AP mice than the controls. AP suppressed the expression of MuRF1,
      but upregulated both myosin heavy chain (MHC) and MHC type IIb. AP also
      significantly suppressed expression of tumor necrosis-alpha in the gastrocnemius
      and soleus muscles, and interleukin-6 expression in the soleus muscle.
      DISCUSSION: AP appears to inhibit denervation-induced muscle atrophy, which may
      be due in part to its inhibitory effect on inflammatory processes within muscle.
      Muscle Nerve 58: 314-318, 2018.

PMID- 29572869
TI  - A new approach to assess the effect of photodamage on corneocyte envelope
      maturity using combined hydrophobicity and mechanical fragility assays.
AB  - BACKGROUND: The maturity of the corneocyte envelope (CE) provides information
      about the barrier functionality of the stratum corneum (SC). Corneocytes are
      enclosed by the CE, a protein-lipid matrix, contributing to mechanical resistance
      and hydrophobicity of the SC. OBJECTIVES: The aim of the work was to develop a
      novel and robust approach to characterize CE maturity based on rigidity,
      hydrophobicity and surface area. This offers an alternative approach to the Nile
      red staining and antigenicity of involucrin to characterize the CE. The
      photoexposed (PE) cheek and photoprotected (PP) post-auricular sites were
      selected for investigation. METHODS: Nine tape strips were obtained from the
      cheek and post-auricular sites of healthy Caucasians. CEs on the first and last
      tape strip were subjected to sonication to assess rigidity, and Nile red staining
      to determine hydrophobicity per unit surface area. In addition, the presence of
      involucrin and lipids was assessed to determine CE maturity by examination of the
      red/green pixel ratio, percentage of involucrin expressing CEs and alternatively
      the ratio of fluorescence density. RESULTS: The CE rigidity was lower in the
      deeper SC layers of the cheek, whereas post-auricular CEs were mechanically more
      resistant. Post-auricular CEs from the superficial SC had a larger surface area
      with a stronger fluorescence signal than those from the cheek. Interestingly,
      those CEs from the deeper SC layers had similar surface areas in both anatomical
      sites but were significantly different in hydrophobicity. These three parameters
      can be summarized as a relative CE maturity index that expresses CE maturity more
      precisely with a higher sensitivity than the conventional involucrin and Nile red
      staining approach. CEs of the cheek surface are more mature than CEs in the
      deeper SC layer, whereas CEs obtained from the post-auricular surface are more
      mature than those from the cheek surface. CONCLUSION: The combined method
      developed allows characterization of CE maturity based on hydrophobicity per unit
      surface area and rigidity rather than a simple ratio of lipid to involucrin. A
      more robust and sensitive measurement has therefore been developed addressing the
      limitations of earlier protocols.

PMID- 29572870
TI  - Omics approaches for food authentication.
AB  - The development of analytical strategies to fight against food fraud is currently
      one of the most developing fields in food science as the food value chain becomes
      increasingly complex and global. Food can be certified by clear labeling but also
      by objective analytical methods. As shown recently by several groups, the omics
      technologies such as genomics, proteomics, metabolomics, and isotopolomics are
      suitable to prove the geographical origin, the production or cultivation process,
      and the biological and the overall chemical identity of food. This article
      describes different analytical approaches beginning with non-targeted strategies
      as well as the further developmental stages of transferring the methods to
      routine laboratories.

PMID- 29572871
TI  - A preliminary origin-tracking study of different densities urinary exosomes.
AB  - Based on density differences of different subpopulations of exosomes, two kinds
      of micro-vesicles with different densities were captured from urine by a modified
      sucrose density gradient ultracentrifuge separation method. Verified by
      transmission electron microscope (TEM) and western blot, the results showed these
      two kinds of micro-vesicles were all exosomes. And these two kinds of exosomes
      were analyzed by TEM, 2D electrophoresis (2DE), and capillary zone
      electrophoresis (CZE), respectively. The results of TEM showed these two exosomes
      with different densities have different morphological characteristics, and some
      tiny proteomic differences were shown in the results of 2DE of these two
      exosomes. At the same time, the CZE results displayed these two kinds of exosomes
      possessed different retention times, indicated that they may have different
      electrification property and particle weight. These results may attribute to
      their different origins. This work may provide a preliminary experience for the
      origin-tracking study for urinary exosomes, and would be more useful for future
      targeted biomarker discovery.

PMID- 29572872
TI  - Differential transcriptome analysis of zebrafish (Danio rerio) larvae challenged
      by Vibrio parahaemolyticus.
AB  - Zebrafish embryo and larva represent a useful in vivo model for identification of
      host innate immune responses to bacterial infection. Vibrio parahaemolyticus is a
      typical zoonotic pathogen worldwide that causes acute gastroenteritis in humans
      and vibriosis in fishes. However, the mechanism of the innate immune response in
      the zebrafish larvae infected by V. parahaemolyticus has not been clear. We
      analysed the transcriptomic profile of 3 days post-fertilization (dpf) zebrafish
      larvae immersed in V. parahaemolyticus 13 (Vp13) strain suspension for 2 hr. A
      total of 602 differentially expressed genes (DEGs) were identified in the
      infection group, of which 175 (29.07%) genes were upregulated and 427 (70.93%)
      genes were downregulated. These altered genes encoded complement and coagulation
      cascades, chemokine, TNF signalling pathway, NF-kappaB signalling pathway and JAK
      STAT signalling pathway. Some significant DEGs, such as mmp13, cxcr4a, ccl20,
      hsp70, gngt, serpina1l, il8, cofilin and il11, were subjected to quantitative
      gene expression analysis, and the results were consistent with those of the
      transcriptome profile. These results clearly demonstrated that exposure to V.
      parahaemolyticus for 2 hr could activate innate immune response in 3dpf larvae by
      altered expression of downstream signalling pathway genes of pattern recognition
      receptors (PRRs). Our results also provide a useful reference for future analysis
      of signal transduction pathways and pathogenesis mechanisms underlying the
      systemic innate immune response to the external bacteria of V. parahaemolyticus.

PMID- 29572873
TI  - Characterizing cardiac dysfunction in fetuses with left congenital diaphragmatic
      hernia.
AB  - OBJECTIVE: To evaluate cardiac function by conventional echocardiography and
      tissue Doppler imaging in fetuses with left congenital diaphragmatic hernia
      (CDH). METHODS: Conventional echocardiography (myocardial performance index,
      ventricular filling velocities, and E/A ratios) and tissue Doppler imaging
      (annular myocardial peak velocities, E/E' and E'/A' ratios) in mitral, septal,
      and tricuspid annulus were evaluated in a cohort of 31 left-sided CDH fetuses and
      compared with 75 controls matched for gestational age 2:1. RESULTS: In comparison
      to controls, CDH fetuses had prolonged isovolumetric time periods (isovolumetric
      contraction time 35 ms vs 28 ms, P < .001), with higher myocardial performance
      index (0.49 vs 0.42, P < .001) and tricuspid E/A ratios (0.77 vs 0.72, P = .033).
      Longitudinal function assessed by tissue Doppler showed signs of impaired
      relaxation (mitral lateral A' 8.0 vs 10.1 cm/s, P < .001 and an increased mitral
      lateral E'/A' ratio 0.93 vs 0.78, P < .001) in the CDH fetuses as compared with
      controls, with preserved systolic function. CONCLUSION: Left CDH fetuses show
      echocardiographic signs of diastolic dysfunction, probably secondary to fetal
      heart compression, maintaining a preserved systolic function.

PMID- 29572874
TI  - Determination of ellagic acid by capillary electrophoresis in Argentinian wines.
AB  - Rising interest in ellagic acid (EA) present in functional foods is supported by
      its antimutagenic, anticarcinogenic, antiviral, antibacterial and antioxidative
      effects. The present approach presents for the first time the determination of
      ellagic acid and other phenolics in wines by miniaturized solid phase extraction
      prior to capillary zone electrophoresis (CZE) with UV. The extraction was
      performed using a home-made miniaturized pipette tip column. The procedure
      allowed a significant reduction in conditioning/sample/washing/elution volumes.
      The effects of important factors affecting the extraction efficiency as well as
      electrophoretic performance were investigated to acquire optimum conditions. The
      analytes were separated within 10 min with a BGE containing 30 mmol/L sodium
      tetraborate 10% v/v MeOH pH 9.10. The optimized method was applied to the
      determination of ellagic acid in commercial and pilot-scale wines. Indeed, the
      content of EA was correlated with viticultural parameters such as grape varietal,
      production area, and aging conditions (oak wood guard and glass bottle ward). In
      order to validate the results, a comparison between the CZE and HPLC data was
      made.

PMID- 29572875
TI  - Unmasking the silent motor neuron loss in amyotrophic lateral sclerosis.

PMID- 29572877
TI  - Preparation and identification of oligosaccharides in lotus seeds and
      determination of their distribution in different parts of lotus.
AB  - Three fractions (I-III) were separated from crude oligosaccharides of lotus seeds
      by fast protein liquid chromatography with final purity of 97.6, 96.3, and 96.8%,
      respectively. The fractions were identified as sucrose, raffinose, and stachyose
      by using TLC, HPLC with charged aerosol detector (CAD), LC-MS, and methylation
      analysis. Subsequently sucrose and raffinose family oligosaccharides (RFOs) with
      degree of polymerization (DP) 3-5 (raffinose, stachyose, and verbascose) have
      been quantified by HPLC-CAD for the first time. All calibration curves for
      investigated analytes showed good linear regression (R2  > 0.9952). Their limit
      of detection and limit of quantity were in the ranges 0.14-0.28 and 0.36-0.48
      MUg/mL, respectively. The recoveries ranged from 96.6 to 103.4%. The contents of
      sucrose and RFOs DP3-DP5 were different in lotus seeds and other parts of lotus
      samples, but similar in their own variety. Additionally, the distribution of RFOs
      in different parts of lotus were also compared and the results indicated that
      RFOs might be mainly synthesized in lotus seeds. This work is helpful for
      understanding the way of biosynthesis of RFOs in lotus as well as quality control
      of plants containing RFOs.

PMID- 29572876
TI  - Research advances based on mass spectrometry for profiling of triacylglycerols in
      oils and fats and their applications.
AB  - Vegetable oils and animal fats are dietary source of lipids that play critical
      and multiple roles in biological function. Triacylglycerols (TAGs) are the
      principal component of oils and fats with significant difference in profile among
      different oils and fats. TAG profiling is essential for nutritional evaluation,
      quality control and assurance of safety in oils and fats. However, analysis of
      TAGs is a challenging task because of the complicated composition of TAGs and
      their similar physicochemical properties in oils and fats. The rapid development
      of mass spectrometry (MS) technology in recent years makes it possible to analyze
      the composition, content and structure of TAGs in the study of the physical,
      chemical and nutritional properties of oils, fats and related products. This
      review described the research advancement based on MS for profiling of TAGs in
      oil, fat and their applications in food. The application of MS, including direct
      infusion strategies, and its combination with chromatography, gas chromatography
      MS (GC-MS) and liquid chromatography-MS (LC-MS), in the analysis of TAGs were
      reviewed. The advantages and disadvantages of these analytical methods with
      relevant applications for TAGs analysis in food were also described.

PMID- 29572878
TI  - Muscle contractures in patients with cerebral palsy and acquired brain injury are
      associated with extracellular matrix expansion, pro-inflammatory gene expression,
      and reduced rRNA synthesis.
AB  - INTRODUCTION: Children with cerebral palsy (CP) and acquired brain injury (ABI)
      commonly develop muscle contractures with advancing age. An underlying growth
      defect contributing to skeletal muscle contracture formation in CP/ABI has been
      suggested. METHODS: The biceps muscles of children and adolescents with CP/ABI (n
      = 20) and typically developing controls (n = 10) were investigated. We used
      immunohistochemistry, quantitative real-time polymerase chain reaction, and
      Western blotting to assess gene expression relevant to growth and size
      homeostasis. RESULTS: Classical pro-inflammatory cytokines and genes involved in
      extracellular matrix (ECM) production were elevated in skeletal muscle of
      children with CP/ABI. Intramuscular collagen content was increased and satellite
      cell number decreased and this was associated with reduced levels of RNA
      polymerase I transcription factors, 45s pre-rRNA and 28S rRNA. DISCUSSION: The
      present study provides novel data suggesting a role for pro-inflammatory
      cytokines and reduced ribosomal production in the development/maintenance of
      muscle contractures, possibly underlying stunted growth and perimysial ECM
      expansion. Muscle Nerve 58: 277-285, 2018.

PMID- 29572879
TI  - Patient-Specific Atrial Hemodynamics of a Double Lumen Neonatal Cannula in
      Correct Caval Position.
AB  - Clinical success of pediatric veno-venous (VV) extracorporeal membrane
      oxygenation (ECMO) is associated with the double lumen cannula cardiovascular
      device design as well as its anatomic orientation in the atrium. The positions of
      cannula ports with respect to the vena cavae and the tricuspid valve are believed
      to play a significant role on device hemodynamics. Despite various improvements
      in ECMO catheters, especially for the neonatal and congenital heart patients, it
      is still challenging to select a catalogue size that would fit to most patients
      optimally. In effect, the local unfavorable blood flow characteristics of the
      cannula would translate to an overall loss of efficiency of the ECMO circuit. In
      this study, the complex flow regime of a neonatal double lumen cannula,
      positioned in a patient-specific right atrium, is presented for the first time in
      literature. A pulsatile computational fluid dynamics (CFD) solver that is
      validated for cardiovascular device flow regimes was used to perform the detailed
      flow, oxygenated blood transport, and site-specific blood damage analysis using
      an integrated cannula and right atrium model. A standard 13Fr double lumen
      cannula was scanned using micro-CT, reconstructed and simulated under physiologic
      flow conditions. User defined scalar transport equations allowed the
      quantification of the mixing and convection of oxygenated and deoxygenated blood
      as well as blood residence times and hemolysis build-up. Site-specific CFD
      analysis provided key insight into the hemodynamic challenges encountered in
      cannula design and the associated intra-atrial flow patterns. Due to neonatal
      flow conditions, an ultra high velocity infusion jet emanated from the infusion
      port and created a zone of major recirculation in the atrium. This flow regime
      influenced the delivery of the oxygenated blood to the tricuspid valve. Elevated
      velocities and complex gradients resulted in higher wall shear stresses (WSS)
      particularly at the infusion port having the highest value followed by the
      aspiration hole closest to the drainage port. Our results show that, in a cannula
      that is perfectly oriented in the atrium, almost 38% of the oxygenated blood is
      lost to the atrial circulation while only half of the blood from inferior vena
      cava (IVC) can reach to the tricuspid valve. As such, approximately 6% of venous
      blood from superior vena cava (SVC) can be delivered to tricuspid. High values of
      hemolysis index were observed with blood damage encountered around infusion hole
      (0.025%). These results warrant further improvements in the cannula design to
      achieve optimal performance of ECMO and better patient outcomes.

PMID- 29572880
TI  - Postoperative ergometry-guided programming does not prevent T-wave oversensing
      and inappropriate shocks in S-ICD patients.
AB  - BACKGROUND: T-wave oversensing (TWOS) is a feared complication after subcutaneous
      implantable cardioverter-defibrillator (S-ICD) implantation, potentially leading
      to inappropriate shocks (IS) with tremendous impact on quality of life.
      HYPOTHESIS: Postoperative ergometry facilitates primary and secondary prevention
      of TWOS or other potential causes of IS and optimizes S-ICD programming. METHODS:
      We analyze the impact of ergometry guided-programming (EMGP) on primary and
      secondary prevention of TWOS/IS in S-ICD patients, we screened 146 patients
      implanted in our center (2010-2016) for the incidence of TWOS/IS during
      postoperative ergometry. Furthermore, to evaluate the outcome in 123 eligible
      patients complete follow-up (FU) of at least 6 months up to 2 years was
      retrospectively analyzed. RESULTS: (1) Primary prevention: TWOS could only be
      provoked postoperatively in 3.7% of patients (n = 3/82). FU analyses did not
      reveal significant differences compared to our control group (Ctrl: n = 6/61,
      9.8% vs EMGP: n = 5/62, 8.1%; P = 0.731). Further subgroup analyses of patients
      with postoperative ergometry in the close postoperative period (< 7 days; n =
      3/45, 6.7%; P = 0.563) did not yield any significant difference. (2) Secondary
      prevention: We found various causes of TWOS/IS. In patients who underwent
      reprogramming due to previous TWOS/IS events we observed a 66.7% (n = 6/9)
      reduction of TWOS/IS using EMGP. CONCLUSION: TWOS/IS has various causes while not
      all cases are exercise-associated. Postoperative ergometry does not seem to be
      useful for primary prevention. Further trials need to investigate the potential
      benefit of EMGP for secondary prevention of TWOS/IS.

PMID- 29572881
TI  - Day-case device implantation-A prospective single-center experience including
      patient satisfaction data.
AB  - PURPOSE: Many centers perform day-case cardiac rhythm management (CRM) device
      implantation. However, there is a paucity of prospective data concerning this
      approach. We performed a prospective single-center study of day-case device
      implantation, including data on patient satisfaction. METHODS: All patients
      scheduled for a new elective device were considered for a day-case procedure.
      Exclusion criteria were living alone or without a suitable carer, advancing
      age/frailty, a metallic valve, and persistent complete heart block. Following
      discharge, patients were reviewed in device clinic at 6 weeks with an anonymized
      questionnaire. RESULTS: During the study period (May 2014-August 2016), 797 new
      CRM devices were implanted. Of these, 232 were elective and included in the
      analysis; 101 were planned to be day-case and 131 scheduled for overnight stay.
      Of the 101 day-case patients, 52 had a pacemaker, 28 an implantable cardioverter
      defibrillator (ICD), 16 a cardiac resynchronization therapy
      pacemaker/defibrillator, and five a subcutaneous-ICD. Complications were similar
      in the day-case (n  =  12, 12%) and overnight stay (n  =  15, 11%) groups (P  = 
      0.92). In the day-case group, 93 (92%) patients went home the same day. An
      estimated 111 overnight bed days were saved, translating to a cost saving of
      L61,912 (euro 70,767, $79,211). Note that 99% (n  =  100) of patients returned
      the questionnaire. Patient satisfaction was universally high. The majority (n  = 
      98, 98%) felt ready to go home on discharge; only a minority (n  =  5, 5%) would
      have preferred an overnight stay. CONCLUSIONS: A significant proportion of
      elective new CRM device implants can be performed as day-case procedures. With
      appropriate selection patient acceptability of same-day discharge is high.

PMID- 29572882
TI  - Failure to shock: What is the mechanism?
AB  - BACKGROUND: The Biotronik DX lead is an attractive option due to its floating
      atrial bipole and its noninferiority compared to dual-chamber defibrillators.
      METHODS: We describe the case of atrial undersensing by the DX lead resulting in
      failure of the device to appropriately treat a slow ventricular tachycardia.
      CONCLUSION: This case underlies the importance of understanding the limitations
      to each lead technology as well as the underlying assumptions inherent to
      detection enhancement algorithms.

PMID- 29572883
TI  - The effects of inactivation methods of Yersinia ruckeri on the efficacy of single
      dip vaccination in Atlantic salmon (Salmo salar).

PMID- 29572884
TI  - Transient elastography is an unreliable marker of liver fibrosis in patients with
      portal vein thrombosis.

PMID- 29572885
TI  - Health problems associated with irritable bowel syndrome: analysis of a primary
      care registry.
AB  - BACKGROUND: Associations between irritable bowel syndrome and other health
      problems have been described, but comprehensive reports are missing, especially
      in primary care. AIMS: To investigate which health problems are associated with
      irritable bowel syndrome, how they cluster together and when they are typically
      diagnosed relative to irritable bowel syndrome. METHODS: We used Intego, a
      general practice registry in Flanders, Belgium. Patients with an irritable bowel
      syndrome diagnosis (n = 13 701) were matched with controls without
      gastrointestinal diagnosis and controls with organic gastrointestinal disease.
      Long-term prevalences of 680 symptoms and diagnoses were compared between
      patients and controls. Results were summarised using functional enrichment
      analysis and visualised in a network and we calculated incidence rate ratios in
      the 10 years before and after the irritable bowel syndrome diagnosis for the
      network's key components. RESULTS: Various symptoms and infections, but not
      neoplasms, were enriched in irritable bowel syndrome patients compared to both
      control groups. We characterised the comorbidities of irritable bowel syndrome as
      psychosocial health problems, urogenital symptoms and infections, musculoskeletal
      symptoms and other somatic symptoms. These had a uniform incidence in the years
      around the irritable bowel syndrome diagnosis, and did not structurally precede
      or follow irritable bowel syndrome. CONCLUSIONS: Irritable bowel syndrome shares
      long-term associations with psychosocial health problems, urogenital symptoms and
      infections, musculoskeletal symptoms and other somatic symptoms in primary care.
      Clinicians are encouraged to take comorbidities into account when diagnosing and
      managing irritable bowel syndrome, as this may have important treatment
      implications.

PMID- 29572887
TI  - Fibromyalgia syndrome and small fiber, early or mild sensory polyneuropathy.
AB  - INTRODUCTION: Pain mechanisms in fibromyalgia syndrome (FMS) are not clearly
      understood. Growing evidence appears to suggest a role for small fiber
      polyneuropathy (SFPN) in some FMS patients, as measured by epidermal nerve fiber
      density (ENFD). We aimed to better characterize and distinguish the subset of
      patients with both fibromyalgia and small fiber, early or mild sensory
      polyneuropathy (FM-SFSPN). METHODS: 155 FMS patients with neuropathic symptoms
      completed a Short Form McGill Questionnaire and visual analog scale in addition
      to having skin biopsies, nerve conduction studies (NCS), and serologic testing.
      RESULTS: Sural and medial plantar (MP) response amplitudes correlated with ENFD,
      with markers of metabolic syndrome being more prevalent in this subset of
      patients. Pain intensity and quality did not distinguish patients. DISCUSSION:
      The FM-SFSPN subset of patients may be identified through sural and MP sensory
      NCS and/or skin biopsy but cannot be identified by pain features and intensity.
      Muscle Nerve 58: 625-630, 2018.

PMID- 29572886
TI  - Impact of culture on autobiographical life structure in depression.
AB  - OBJECTIVES: Distortions in autobiographical memory have been implicated in major
      depressive disorder (MDD). Those with MDD demonstrate a 'depressogenic'
      autobiographical life structure. Research has not examined how culture influences
      this process. We investigated whether Malay individuals (members of an
      interdependent culture) with MDD demonstrated a 'depressogenic' autobiographical
      life structure similar to that of British individuals (members of an independent
      culture) with MDD. DESIGN: A 2 (Culture; Malay, British) * 2 (Mood; depressed,
      control) cross-sectional design using a card sort task and self-report measures
      was used. METHODS: Malay individuals with MDD or no history of MDD completed the
      life-structure card-sorting task, which provided a novel method for investigating
      organizational structure of the life narrative. These data were compared to
      previously collected data in which British individuals with MDD or without MDD
      had completed the same task within the same experimental protocol. RESULTS: Pan
      culturally those with MDD had greater negativity (i.e., used more negative
      attributes), negative redundancy (i.e., used the same negative attributes
      repeatedly across life chapters) and negative emodiversity (i.e., had greater
      variety and relative abundance of negative attributes), and reduced positive
      redundancy (i.e., used the same positive attributes repeatedly across chapters)
      in their structuring relative to controls. While the British MDD group had
      greater compartmentalization (i.e., the negative and positive attributes were
      clustered separately across different chapters) than British controls, the Malay
      MDD group had lower levels of compartmentalization than Malay controls.
      CONCLUSIONS: The findings suggest culture may shape aspects of the
      autobiographical life structure in MDD. PRACTITIONER POINTS: The majority of the
      literature investigating depression pertains to individuals from European Western
      cultures, despite recognition that depression ranks as one of the most
      debilitating diseases worldwide. This raises questions as to whether current
      depression models and interventions can be applied universally or whether they
      are limited to European Western groups. The current study found that pan
      culturally those with MDD had similar structuring of their life story relative to
      controls. However, there were some cultural differences that need to be
      considered (e.g., Malay individuals provided less detailed, less elaborate and
      less emotionally diverse life stories and while the British MDD group had greater
      compartmentalization than British controls, the Malay MDD group had lower levels
      of compartmentalization than Malay controls). Limitations of the study included
      group differences in gender and mood at the time of testing. Cultural differences
      in the number of attributes used may have influenced findings. Only the Malay
      group completed the individualism-collectivism measure.

PMID- 29572888
TI  - PRDM8 exhibits antitumor activities toward hepatocellular carcinoma by targeting
      NAP1L1.
AB  - : Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality
      worldwide. PRDI-BF1 and RIZ homology domain containing 8 (PRDM8) is a key
      regulator in neural development and testis steroidogenesis; however, its role in
      liver carcinogenesis remains to be investigated. In this study, PRDM8 was found
      to be down-regulated in HCC, which was linked with shorter recurrence-free
      survival. Lentiviral-based overexpression and knockdown approaches showed that
      PRDM8 inhibited HCC cell proliferation, migration, and invasion. PRDM8 caused
      G1/S cell cycle arrest and induced apoptosis. An in vivo tumor model confirmed
      the antitumor role of PRDM8 in HCC growth and metastasis. Mechanistic study
      showed that PRDM8 suppressed the PI3K/AKT/mTOR signaling cascade through the
      regulation of nucleosome assembly protein 1-like 1 (NAP1L1). CONCLUSION: PRDM8 as
      a functional tumor suppressor is frequently down-regulated in HCC. Through
      regulating NAP1L1, PRDM8 inhibits PI3K/AKT/mTOR signaling in HCC. PRDM8 is a
      potential target for novel therapies of HCC. (Hepatology 2018).

PMID- 29572889
TI  - Risk factors for diagnostic delay in Crohn's disease and their impact on long
      term complications: how do they differ in a tuberculosis endemic region?
AB  - BACKGROUND: The diagnosis of Crohn's disease (CD) can be delayed in clinical
      practice. In tuberculosis endemic areas, empirical anti-tubercular therapy
      further delays treatment. AIM(S): To assess risk factors for diagnostic delay and
      its impact on the long-term complications of Crohn's disease in India where
      tuberculosis is endemic. METHODS: Data from a large prospectively established
      inflammatory bowel disease registry were analysed retrospectively. The time from
      onset of symptoms to diagnosis (diagnostic delay) was calculated and categorised
      into two groups based on median diagnostic delay. The risk factors for delay
      including anti-tubercular therapy were analysed. Logistic regression analysis was
      done to assess impact of diagnostic delay on development of stenotic and fistular
      complications including need for surgery. RESULTS: Seven hundred and twenty
      Crohn's disease patients (60.3% male, median: 28 years) were included. Main
      outcome measures were stenosis, fistula and need for surgery. Subjects with
      diagnostic delay >18 months (median) developed significantly higher stenotic
      complications and surgery (OR 4.12; 95% CI: 2.74-6.33, P < 0.001 and OR 2.41, 95%
      CI: 1.68-3.42, P < 0.001), respectively, compared to those <=18 months. There was
      no difference in the development of fistulous complications. 193/720 (27%)
      received anti-tubercular therapy which significantly contributed to diagnostic
      delay (OR: 2.47; 95% CI: 1.76-3.47, P < 0.001) with 47% showing initial clinical
      response (Crohn's disease activity index- CDAI decrease >100). Moreover, the
      incidence of stenotic complications was significantly higher in patients who had
      received prior anti-tubercular therapy (55/193 (28.49%) vs 78/527 (14.8%), P <
      0.001, OR: 2.60, 95% CI: 1.64-4.12). CONCLUSIONS: Diagnostic delay in Crohn's
      disease is associated with significantly higher stenotic complications and need
      for surgery. Empirical anti-tubercular therapy is the single largest contributor
      to diagnostic delay in tuberculosis endemic areas. Despite initial clinical
      response to anti-tubercular therapy, long-term stenotic complications are higher.

PMID- 29572890
TI  - A general approach to evaluating the bias of 2-stage instrumental variable
      estimators.
AB  - Unmeasured confounding is a common concern when researchers attempt to estimate a
      treatment effect using observational data or randomized studies with nonperfect
      compliance. To address this concern, instrumental variable methods, such as 2
      stage predictor substitution (2SPS) and 2-stage residual inclusion (2SRI), have
      been widely adopted. In many clinical studies of binary and survival outcomes,
      2SRI has been accepted as the method of choice over 2SPS, but a compelling
      theoretical rationale has not been postulated. We evaluate the bias and
      consistency in estimating the conditional treatment effect for both 2SPS and 2SRI
      when the outcome is binary, count, or time to event. We demonstrate analytically
      that the bias in 2SPS and 2SRI estimators can be reframed to mirror the problem
      of omitted variables in nonlinear models and that there is a direct relationship
      with the collapsibility of effect measures. In contrast to conclusions made by
      previous studies (Terza et al, 2008), we demonstrate that the consistency of 2SRI
      estimators only holds under the following conditions: (1) when the null
      hypothesis is true; (2) when the outcome model is collapsible; or (3) when
      estimating the nonnull causal effect from Cox or logistic regression models, the
      strong and unrealistic assumption that the effect of the unmeasured covariates on
      the treatment is proportional to their effect on the outcome needs to hold. We
      propose a novel dissimilarity metric to provide an intuitive explanation of the
      bias of 2SRI estimators in noncollapsible models and demonstrate that with
      increasing dissimilarity between the effects of the unmeasured covariates on the
      treatment versus outcome, the bias of 2SRI increases in magnitude.

PMID- 29572891
TI  - Link between gut-microbiome derived metabolite and shared gene-effects with
      hepatic steatosis and fibrosis in NAFLD.
AB  - : Previous studies have shown that gut-microbiome is associated with nonalcoholic
      fatty liver disease (NAFLD). We aimed to examine if serum metabolites, especially
      those derived from the gut-microbiome, have a shared gene-effect with hepatic
      steatosis and fibrosis. This is a cross-sectional analysis of a prospective
      discovery cohort including 156 well-characterized twins and families with
      untargeted metabolome profiling assessment. Hepatic steatosis was assessed using
      magnetic-resonance-imaging proton-density-fat-fraction (MRI-PDFF) and fibrosis
      using MR-elastography (MRE). A twin additive genetics and unique environment
      effects (AE) model was used to estimate the shared gene-effect between
      metabolites and hepatic steatosis and fibrosis. The findings were validated in an
      independent prospective validation cohort of 156 participants with biopsy-proven
      NAFLD including shotgun metagenomics sequencing assessment in a subgroup of the
      cohort. In the discovery cohort, 56 metabolites including 6 microbial metabolites
      had a significant shared gene-effect with both hepatic steatosis and fibrosis
      after adjustment for age, sex and ethnicity. In the validation cohort, 6
      metabolites were associated with advanced fibrosis. Among them, only one
      microbial metabolite, 3-(4-hydroxyphenyl)lactate, remained consistent and
      statistically significantly associated with liver fibrosis in the discovery and
      validation cohort (fold-change of higher-MRE versus lower-MRE: 1.78, P < 0.001
      and of advanced versus no advanced fibrosis: 1.26, P = 0.037, respectively). The
      share genetic determination of 3-(4-hydroxyphenyl)lactate with hepatic steatosis
      was RG :0.57,95%CI:0.27-0.80, P < 0.001 and with fibrosis was RG
      :0.54,95%CI:0.036-1, P = 0.036. Pathway reconstruction linked 3-(4
      hydroxyphenyl)lactate to several human gut-microbiome species. In the validation
      cohort, 3-(4-hydroxyphenyl)lactate was significantly correlated with the
      abundance of several gut-microbiome species, belonging only to Firmicutes,
      Bacteroidetes and Proteobacteria phyla, previously reported as associated with
      advanced fibrosis. CONCLUSION: This proof of concept study provides evidence of a
      link between the gut-microbiome and 3-(4-hydroxyphenyl)lactate that shares gene
      effect with hepatic steatosis and fibrosis. (Hepatology 2018).

PMID- 29572893
TI  - Subchronic cadmium exposure upregulates the mRNA level of genes associated to
      hepatic lipid metabolism in adult female CD1 mice.
AB  - Cadmium (Cd) is a persistent environmental and occupational contaminant that
      accumulates in humans and shows adverse effects on health. Accumulating evidence
      reveals that environmental Cd exposure is associated with hepatic lipid
      accumulation and metabolic alterations in adult male mice. However, whether Cd
      exposure induces hepatic lipid accumulation and metabolic alterations in female
      mice remains poorly understood. In the present study, we aimed to investigate the
      effects of Cd exposure on insulin resistance, hepatic lipid accumulation and
      associated metabolic pathways. Female CD1 mice were administrated with CdCl2 (10
      and 100 mg l-1 ) by drinking water. We found that Cd exposure did not induce
      obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in
      the Cd-100 mg l-1 group presented a significant reduction of the glucose area
      under the curve during the glucose tolerance test. However, there was a
      significant elevation in the mRNA level of Fasn and Scd-1, which were critical
      genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two
      genes for hepatic fatty acid uptake were upregulated in Cd-treated mice. Of
      interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in
      Cd-treated mice. Collectively, our results suggest that Cd exposure upregulated
      mRNA level of genes related to hepatic lipid metabolism although there was no
      insulin resistance and hepatic lipid accumulation shown in the present study.

PMID- 29572892
TI  - Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated
      inhibition of CCR2.
AB  - : Chronic liver disease mediated by activation of hepatic stellate cells (HSCs)
      and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate
      the molecular mechanism and define the cell type involved in mediating the
      sphingosine kinase (SphK)1-dependent effect on liver fibrosis. The levels of
      expression and activity of SphK1 were significantly increased in fibrotic livers
      compared with the normal livers in human. SphK1 was coexpressed with a range of
      HSC/KC markers including desmin, alpha-smooth muscle actin (alpha-SMA) and F4/80
      in fibrotic liver. Deficiency of SphK1 (SphK1-/- ) resulted in a marked
      amelioration of hepatic injury, including transaminase activities, histology,
      collagen deposition, alpha-SMA and inflammation, in CCl4 or bile duct ligation
      (BDL)-induced mice. Likewise, treatment with a specific inhibitor of SphK1, 5C,
      also significantly prevented liver injury and fibrosis in mice induced by CCl4 or
      BDL. In cellular levels, inhibition of SphK1 significantly blocked the activation
      and migration of HSCs and KCs. Moreover, SphK1 knockout in KCs reduced the
      secretion of CCL2, and SphK1 knockout in HSCs reduced C-C motif chemokine
      receptor 2 ([CCR2] CCL2 receptor) expression in HSCs. CCL2 in SphK1-/- mice was
      lower whereas microRNA-19b-3p in SphK1-/- mice was higher compared with wild-type
      (WT) mice. Furthermore, microRNA-19b-3p downregulated CCR2 in HSCs. The
      functional effect of SphK1 in HSCs on liver fibrosis was further strengthened by
      the results of animal experiments using a bone marrow transplantation (BMT)
      method. CONCLUSION: SphK1 has distinct roles in the activation of KCs and HSCs in
      liver fibrosis. Mechanistically, SphK1 in KCs mediates CCL2 secretion, and SphK1
      in HSCs upregulates CCR2 by downregulation of miR-19b-3p. (Hepatology 2018).

PMID- 29572895
TI  - NIOSH remembers James Melius, M.D., Dr.P.H.

PMID- 29572894
TI  - Regulatory gene network from a genome-wide association study for sow lifetime
      productivity traits.
AB  - Among swine reproductive traits, sow lifetime productivity (SLP) is considered a
      profitable trait in commercial pig farming. Notably, longevity and efficiency in
      SLP can be adopted as the key phenotype representing SLP. In this study, we
      conducted a co-association network analysis using results from a genome-wide
      association study for SLP-related traits. A total of 656 purebred Landrace female
      pigs were genotyped using a 60K SNP array. Significantly associated SNPs
      identified from the GWAS were annotated for the specific genes. Then, we
      constructed an association weight matrix to build a network based on the co
      associations between the genes and 10 SLP traits. The entire network consisted of
      495 nodes and 37 755 significant edges. We identified three key regulatory
      transcription factors: STAT2 (signal transducer and activator of transcription
      2), MYF6 (myogenic factor 6) and TFCP2L1 (transcription factor CP2 like 1). The
      network revealed that the STAT2 and MYF6 regulatory modules cooperate with each
      other and specifically influence the longevity and efficiency of sows, whereas
      the TFCP2L1 family specifically affects the improvement of litter size.

PMID- 29572896
TI  - Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog
      hepatocellular adenomas.
AB  - : Genetic alterations define different molecular subclasses of hepatocellular
      adenoma (HCA) linked with risk factors, histology and clinical behavior.
      Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was
      proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess
      the significance of ASS1 expression through the scope of the HCA molecular
      classification. ASS1 expression was evaluated using RNAseq, quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) and Immunohistochemistry. ASS1
      and glioma-associated oncogene 1 (GLI1) expression were analyzed in vitro after
      modulation of GLI1 expression. Using RNAseq in 27 HCA and five nontumor liver
      samples, ASS1 expression was highly correlated with GLI1 expression (P<0.0001,
      R=0.75). In the overall series of 408 HCA, ASS1 overexpression was significantly
      associated with sonic hedgehog HCA (shHCA) compared to other molecular subgroups
      (P<0.0001), suggesting that sonic hedgehog signaling controls ASS1 expression.
      GLI1 expression silencing by siRNA induced a downregulation of ASS1 in PLC/PFR5
      and SNU878 cell lines. In 390 HCA, we showed that ASS1 expression belonged to the
      periportal expression program that was maintained in shHCA but down-regulated in
      all the other HCA subtypes. In contrast, HCA with beta-catenin activation showed
      an activation of a perivenous program. Despite the significant association
      between GLI1 and ASS1 expression, ASS1 mRNA expression was not associated with
      specific clinical features. At the protein level using immunohistochemistry,
      prostaglandin D synthase (PTGDS) was strongly and specifically overexpressed in
      shHCA. CONCLUSION: ASS1 is associated with sonic hedgehog activation as part of a
      periportal program expressed in shHCA, a molecular subgroup defined by INHBE-GLI1
      gene fusion. (Hepatology 2018).

PMID- 29572898
TI  - James Melius, our colleague and friend.

PMID- 29572897
TI  - Acute hepatitis B virus infection in humanized chimeric mice has multiphasic
      viral kinetics.
AB  - : Chimeric urokinase type plasminogen activator (uPA)/severely severe combined
      immunodeficiency (SCID) mice reconstituted with humanized livers are useful for
      studying hepatitis B virus (HBV) infection in the absence of an adaptive immune
      response. However, the detailed characterization of HBV infection kinetics
      necessary to enable in-depth mechanistic studies in this in vivo HBV infection
      model is lacking. To characterize HBV kinetics post-inoculation (p.i.) to steady
      state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured
      from 1 minute to 63 days p.i. Total intrahepatic HBV DNA, HBV covalently closed
      circular DNA (cccDNA), and HBV RNA was measured in a subset of mice at 2, 4, 6,
      10, and 13 weeks p.i. HBV half-life (t1/2 ) was estimated using a linear mixed
      effects model. During the first 6 hours p.i., serum HBV declined in repopulated
      uPA/SCID mice with a t1/2 = 62 minutes (95% confidence interval [CI] = 59-67).
      Thereafter, viral decline slowed followed by a 2-day lower plateau. Subsequent
      viral amplification was multiphasic with an initial mean doubling time of t2 = 8
      +/- 3 hours followed by an interim plateau before prolonged amplification (t2 = 2
      +/- 0.5 days) to a final HBV steady state of 9.3 +/- 0.3 log copies (cps)/mL.
      Serum HBV and intrahepatic HBV DNA were positively correlated (R2 = 0.98).
      CONCLUSION: HBV infection in uPA/SCID chimeric mice is highly dynamic despite the
      absence of an adaptive immune response. Serum HBV t1/2 in humanized uPA/SCID mice
      was estimated to be ~1 hour regardless of inoculum size. The HBV acute infection
      kinetics presented here is an important step in characterizing this experimental
      model system so that it can be effectively used to elucidate the dynamics of the
      HBV life cycle and thus possibly reveal effective antiviral drug targets.
      (Hepatology 2018).

PMID- 29572899
TI  - In response to CT image navigation patient tracker on the cheek during
      osteoplastic flaps.

PMID- 29572900
TI  - High prevalence and familial aggregation of keratoconus in an Iranian rural
      population: a population-based study.
AB  - PURPOSE: The objective of this study was to determine the prevalence of
      keratoconus and the potential effect of genetic and environmental factors on its
      prevalence in households living in rural areas of Iran in a large population
      based study. METHODS: The present cross-sectional study was performed in two
      Iranian rural populations. Two rural areas were randomly selected in the
      southwest and north of Iran. All individuals over one year of age were invited to
      participate in the study. The study population underwent a thorough eye
      examination, including visual acuity measurement, refraction, slit lamp
      biomicroscopy, and Scheimpflug imaging. The diagnosis of keratoconus was made
      based on Pentacam-specific criteria, tomographic maps, and clinical findings.
      After detecting keratoconus cases, its prevalence in the study population was
      reported as a percentage with a 95% confidence interval (CI). For familial
      aggregation analysis, the odds ratios of keratoconus and its more severe types
      were calculated in different family relationships (siblings, parents-offspring,
      spouses) using second order generalised estimating equation. RESULTS: Of the 3851
      eligible individuals, 3314 subjects participated in the study. After applying the
      exclusion criteria, data from 2667 subjects was used in the analysis. The
      prevalence of keratoconus in the present population was 4% (95% CI: 3-4). The
      odds of keratoconus were significantly higher in males (OR = 2.30, p = 0.032). To
      investigate the familial aggregation of keratoconus, we only evaluated families
      from which at least two members participated in the study. So, 403 families (1452
      participants) were evaluated. Our results showed a higher odds ratio for the
      sibling pairs compare to parent-offspring pairs and as reported, the odds ratio
      of the spouses was less than 1.0. CONCLUSION: Our findings showed a relatively
      high prevalence and familial aggregation of keratoconus in rural areas of Iran,
      independent of age, sex, and place of residence. This aggregation may be due to
      heredity or the effect of undetermined shared environmental factors.

PMID- 29572901
TI  - Do hepatitis B virus surface antigens have any role in viral carcinogenesis?

PMID- 29572902
TI  - 2-fluoro-5-maleimidobenzoic acid-linked albumin drug (MAD) delivery for selective
      systemic targeting of metastatic prostate cancer.
AB  - BACKGROUND: The SH-group at Cys-34 of human serum albumin (HSA) is a unique and
      accessible functional group that can be exploited for efficient linkage of a
      maleimide containing cytotoxic drug derivative to albumin. The specific maleimide
      chemistry used for production of the maleimide-linked albumin drug (MAD) is
      critical, however, to minimize the plasma concentration of "free" cytotoxic drug
      spontaneously released from albumin carrier thus decreasing dose-limiting host
      toxicity while enhancing the plasma half-life from minutes to days (ie,
      pharmacokinetic effect) and tissue concentration of the MAD in the extracellular
      cellular fluid at sites of cancer (ie, EPR effect). METHODS: To accomplish this
      goal, a chemical synthesis was developed using 2-fluoro-5-maleimidobenzoic acid
      to stably link the potent cytotoxic chemically modified analogue of the naturally
      occurring sesquiterpene gamma-lactone, thapsigargin, 8-O-(12-aminododecanoyl)-8-O
      debutanoyl thapsigargin (12ADT), to Cys-34 of albumin to produce 12ADT-MAD.
      RESULTS: Using FITC-labeling, LC/MS analysis, and in vitro growth and clonogenic
      survival assays on a series of 6 human prostate cancer lines (LNCaP, LAPC-4,
      VCap, CWR22Rv 1, PC3, and Du145), we documented that 12ADT-MAD is endocytosed by
      prostate cancer cells where it is degraded into its amino acids liberating
      cysteinyl-maleimide-12ADT which is both chemically stable at the acidic pH of 5.5
      present in the endosome while retaining its high killing ability (IC50 50 nM) via
      SERCA inhibition. CONCLUSIONS: Based upon these positive in vitro validation
      results, the in vivo efficacy versus host toxicity of this 12-ADT-MAD approach is
      presently being evaluated against a series of patient derived androgen responsive
      and castration resistant human xenografts in immune-deficient mice.

PMID- 29572903
TI  - Quantification of metronidazole in human plasma using a highly sensitive and
      rugged LC-MS/MS method for a bioequivalence study.
AB  - A highly sensitive, selective and rugged method has been described for the
      quantification of metronidazole (MTZ) in human plasma by liquid chromatography
      tandem mass spectrometry using metronidazole-d4 as the internal standard (IS).
      The analyte and the IS were extracted from 100 MUL plasma by liquid-liquid
      extraction. The clear samples obtained were chromatographed on an ACE C18 (100 *
      4.6 mm, 5 MUm) column using acetonitrile and 10.0 mm ammonium formate in water,
      pH 4.00 (80:20, v/v) as the mobile phase. A triple quadrupole mass spectrometer
      system equipped with turbo ion spray source and operated in multiple reaction
      monitoring mode was used for the detection and quantification of MTZ. The
      calibration range was established from 0.01 to 10.0 MUg/mL. The results of
      validation testing for precision and accuracy, selectivity, matrix effects,
      recovery and stability complied with current bioanalytical guidelines. A run time
      of 3.0 min permitted analysis of more than 300 samples in a day. The method was
      applied to a bioequivalence study with 250 mg MTZ tablet formulation in 24
      healthy Indian males.

PMID- 29572904
TI  - Promoting resilience through social connection: an intern workshop.

PMID- 29572906
TI  - Epigallocatechin-3-gallate partially restored redox homeostasis in arsenite
      stressed keratinocytes.
AB  - Arsenite (AsIII) is known for inducing severe oxidative stress and skin
      carcinogenesis. Contrastingly, phytochemical, epigallocatechin-3-gallate (EGCG)
      combats toxic insults. Our study focused on the effect of EGCG on redox status of
      AsIII-stressed normal human keratinocytes, HaCaT cells. EGCG (50 MUm) increased
      the cell viability by 29% in AsIII (50 MUm) insulted HaCaT cells but exhibited
      pro-oxidant activity by elevated expression of the oxidative stress markers. EGCG
      was effective not only in reducing AsIII-induced nuclear expression of Nrf2 and
      Nrf2Ser40 but also in increasing nuclear expression of Keap1 both at protein and
      mRNA level. EGCG did not have similar effects on all Nrf2 downstream targets.
      EGCG elevated expression of HO-1 and gamma-GCL,showed no change in MRP1 but
      decreased superoxide dismutase, NAD(P)H dehydrogenase quinone 1 and glutathione S
      transferase activity in AsIII-treated HaCaT cells. EGCG along with AsIII caused
      decreased phosphorylation of Nrf2 at ser40 residue, which might have facilitated
      Keap1-mediated nuclear export and degradation of Nrf2 and paved the pro-survival
      signal for AsIII-insulted HaCaT cells. In conclusion, it might be indicated that
      EGCG in spite of inducing the pro-oxidant effect was effective in increasing the
      viability of AsIII-treated HaCaT cells by partially restoring the Nrf2/Keap1
      mediated signaling axis.

PMID- 29572905
TI  - Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA
      and the viral NS5 protein blocks type I IFN induction and signaling.
AB  - Zika virus (ZIKV) is a major public health concern in the Americas. We report
      that ZIKV infection and RNA extracted from ZIKV infected cells potently activated
      the induction of type I interferons (IFNs). This effect was fully dependent on
      the mitochondrial antiviral signaling protein (MAVS), implicating RIG-I-like
      receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG-I and the related
      RNA sensor MDA5 contributed to type I IFN induction in response to RNA from
      infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked
      type I IFN induction downstream of RLRs and also inhibited type I IFN receptor
      (IFNAR) signaling. We defined the ZIKV NS5 nuclear localization signal and report
      that NS5 nuclear localization was not required for inhibition of signaling
      downstream of IFNAR. Mechanistically, NS5 blocked IFNAR signaling by both leading
      to reduced levels of STAT2 and by blocking phosphorylation of STAT1, two
      transcription factors activated by type I IFNs. Taken together, our observations
      suggest that ZIKV infection induces a type I IFN response via RLRs and that ZIKV
      interferes with this response by blocking signaling downstream of RLRs and IFNAR.

PMID- 29572907
TI  - Climber's knuckle excoriation.

PMID- 29572908
TI  - Causal Analysis in Evaluating Complex Health Interventions: Identifying the
      Optimal Treatment for Opioid Abuse in Pregnancy.

PMID- 29572911
TI  - Peer-assisted learning in scenario-based simulation.

PMID- 29572909
TI  - Mathematical modeling of the adsorption/desorption characteristics of
      anthocyanins from muscadine (Vitis rotundifolia cv. Noble) juice pomace on
      Amberlite FPX66 resin in a fixed bed column.
AB  - BACKGROUND: Muscadine grape pomace, a by-product of juicing and wine-making,
      contains significant amounts of anthocyanin 3,5-diglucosides, known to be
      beneficial to human health. RESULTS: The objective of this research was to use
      mathematical modeling to investigate the adsorption/desorption characteristics of
      these anthocyanins from muscadine grape pomace on Amberlite FPX66 resin in a
      fixed bed column. Anthocyanins were extracted using hot water and ultrasound, and
      the extracts were loaded onto a resin column at five bed depths (5, 6, 8, 10 and
      12 cm) using three flow rates (4, 6 and 8 mL min-1 ). It was found that
      adsorption on the column fitted the bed depth service time (BDST) model and the
      empty bed residence time (EBRT) model. Desorption was achieved by eluting the
      column using ethanol at four concentrations (25, 40, 55 and 70% v/v) and could be
      described with an empirical sigmoid model. The breakthrough curves of
      anthocyanins fitted the BDST model for all three flow rates with R2 values of
      0.983, 0.992 and 0.984 respectively. The EBRT model was successfully employed to
      find the operating lines, which allow for column scale-up while still achieving
      similar results to those found in a laboratory operation. Desorption with 40%
      (v/v) ethanol achieved the highest recovery rate of anthocyanins at 79.6%.
      CONCLUSION: The mathematical models established in this study can be used in
      designing a pilot/industrial- scale column for the separation and concentration
      of anthocyanins from muscadine juice pomace. (c) 2018 Society of Chemical
      Industry.

PMID- 29572912
TI  - Guidance of spatial attention during associative learning: Contributions of
      predictability and intention to learn.
AB  - Expectations of an event can facilitate its neural processing. One of the ways we
      build expectations is through associative learning. Interestingly, the learning
      of contingencies between events can also occur without intention. Here, we study
      feature-based attention during associative learning, by asking how a learned
      association between a cue and a target outcome impacts the attention allocated to
      this outcome. Moreover, we investigate attention in learning depending on the
      intention to learn the association. We used an associative learning paradigm
      where we manipulated outcome predictability and intention to learn an association
      within streams of cue-target outcome visual stimuli, while stimulus
      characteristics and probability were held constant. In order to measure the event
      related component N2pc, widely recognized to reflect allocation of spatial
      attention, every outcome was embedded among distractors. Importantly, the
      location of the target outcome could not be anticipated. We found that
      predictable target outcomes showed an increased spatial attention as indexed by a
      greater N2pc component. A later component, the P300, was sensitive to the
      intention to learn the association between the cue and the target outcome. The
      current study confirms the remarkable ability of the brain to extract and update
      predictive information, in accordance with a predictive-coding model of brain
      function. Associative learning can guide a visual search and shape covert
      attentional selection in our rich environments.

PMID- 29572910
TI  - Na+ -taurocholate cotransporting polypeptide inhibition has hepatoprotective
      effects in cholestasis in mice.
AB  - : Accumulation of bile salts (BSs) during cholestasis leads to hepatic and
      biliary injury, driving inflammatory and fibrotic processes. The Na+ 
      Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake
      transporter of BSs, and can be specifically inhibited by myrcludex B. We
      hypothesized that inhibition of NTCP dampens cholestatic liver injury. Acute
      cholestasis was induced in mice by a 3.5-diethoxycarbonyl-1.4-dihydrocollidine
      (DDC) diet or by bile duct ligation (BDL). Chronic cholestasis was investigated
      in Atp8b1-G308V and Abcb4/Mdr2 deficient mice. Mice were injected daily with
      myrcludex B or vehicle. Myrcludex B reduced plasma alkaline phosphatase (ALP)
      levels in DDC-fed, Atp8b1-G308V and BDL mice by 39%, 27% and 48% respectively.
      Expression of genes involved in fibrosis, proliferation and inflammation was
      reduced by myrcludex B treatment in DDC-fed and Atp8b1-G308V mice. NTCP
      inhibition increased plasma BS levels from 604+/-277 to 1746+/-719 MUm in DDC-fed
      mice, 432+/-280 to 762+/-288 MUm in Atp8b1-G308V mice and from 522+/-130 to
      3625+/-378 MUm in BDL mice. NTCP-inhibition strongly aggravated weight loss in
      BDL mice, but not in other cholestatic models studied. NTCP-inhibition reduced
      biliary BS output in DDC-fed and Atp8b1-G308V mice by ~50% while phospholipid
      (PL) output was maintained, resulting in a higher PL/BS ratio. Conversely, liver
      injury in Abcb4 deficient mice, lacking biliary phospholipid output, was
      aggravated after myrcludex B treatment. CONCLUSION: NTCP-inhibition by myrcludex
      B has hepatoprotective effects, by reducing BS load in hepatocytes and increasing
      the biliary PL/BS ratio. High micromolar plasma BS levels after NTCP-inhibition
      were well tolerated. NTCP-inhibition may be beneficial in selected forms of
      cholestasis. (Hepatology 2018).

PMID- 29572913
TI  - Correlation between electromyography and perineometry in evaluating pelvic floor
      muscle function in nulligravidas: A cross-sectional study.
AB  - OBJECTIVE: To correlate the results of electromyography and perineometry in the
      assessment of PFM function in nulligravidas. METHODS: The cross-sectional
      observational study was approved by the internal review board of the Instituto de
      Medicina Integral Prof. Fernando Figueira (IMIP) and was conducted in the
      Instituto Paraibano de Pesquisa Professor Joaquim Amorim Neto (IPESQ). Thirty
      eight nulligravidas aged 18-39 years of age, who had already initiated their
      sexual life, participated in the study. Exclusion criteria consisted of the
      presence of genital prolapse, a history of pelvic or urogenital surgery and the
      presence of neurological disease producing muscle disorders. For the evaluation
      procedure, the women were submitted to a clinical evaluation of the pelvic floor
      muscles followed by electromyography. Perineometry was performed 72 h later.
      Prior to electromyography and perineometry, the women were given standardized
      training with electromyographic biofeedback to teach them to contract only their
      pelvic floor muscles. RESULTS: A highly positive, statistically significant
      correlation (r = 0.968; P < 0.001) was found between the electromyographic and
      perineometric findings. CONCLUSIONS: A strong correlation was found between
      perineometric and electromyographic findings of pelvic floor muscle function.

PMID- 29572914
TI  - Congenital peristernal dermal sinus: A case report and published work review.

PMID- 29572915
TI  - Developmental conduction aphasia after neonatal stroke.
AB  - OBJECTIVE: Impairment of speech repetition following injury to the dorsal
      language stream is a feature of conduction aphasia, a well-described
      "disconnection syndrome" in adults. The impact of similar lesions sustained in
      infancy has not been established. METHODS: We compared language outcomes in term
      born individuals with confirmed neonatal stroke (n = 30, age = 7-18 years, left
      sided lesions in 21 cases) to matched controls (n = 40). Injury to the dorsal
      and/or ventral language streams was assessed using T1 - and T2 -weighted magnetic
      resonance imaging (MRI) and diffusion tractography. Language lateralization was
      determined using functional MRI. RESULTS: At the group level, left dorsal
      language stream injury was associated with selective speech repetition impairment
      for nonwords (p = 0.021) and sentences (p < 0.0001). The majority of children
      with significant repetition impairment had retained left hemisphere language
      representation, but right hemisphere dominance was correlated with minimal or
      absent repetition deficits. Post hoc analysis of the repetition-impaired group
      revealed additional language-associated deficits, but these were more subtle and
      variable. INTERPRETATION: We conclude that (1) despite the considerable
      plasticity of the infant brain, early dorsal language stream injury can result in
      specific and long-lasting problems with speech repetition that are similar to the
      syndrome of conduction aphasia seen in adults; and (2) language reorganization to
      the contralateral hemisphere has a protective effect. Ann Neurol 2018;83:664-675
      Ann Neurol 2018;83:664-675.

PMID- 29572916
TI  - Open access: Is there a predator at the door?

PMID- 29572919
TI  - A novel, efficient, and ecologically relevant bioassay method using aquatic fungi
      and fungus-like organisms for fungicide ecological effect assessment.
AB  - Fungicides are used to control fungal plant pathogens, but they may also be
      highly toxic to aquatic fungi, which play an important role in natural aquatic
      ecosystems. However, a bioassay method using aquatic fungi has not been
      sufficiently developed. In the present study, a novel, efficient, and
      ecologically relevant bioassay method was developed for the ecological effect
      assessment of fungicides. Candidate test species were selected by considering the
      following 4 factors: 1) their ecological relevance (i.e., widely distributed and
      frequently observed) in freshwater habitats, 2) inclusion of a wide range of
      taxonomic groups, 3) availability from public culture collections, and 4)
      suitability for culture experiments using a microplate. The following 5 fungal
      species were selected: Rhizophydium brooksiaum (Chitridiomycota), Chytriomyces
      hyalinus (Chitridiomycota), Tetracladium setigerum (Ascomycota), Sporobolomyces
      roseus (Basidiomycota), and Aphanomyces stellatus (Oomycota, fungus-like
      organism). An efficient test method using the 5 species was developed based on a
      microplate assay using a 96-well white microplate and a test duration of 48 h.
      Fungal biomass was determined as adenosine 5'-triphosphate (ATP) luminescence,
      which is known to be proportional to live cell density and can be determined with
      a microplate reader. Test performance was evaluated by conducting bioassays of
      3,5-dichlorophenol and malachite green as standard test substances. Fungal
      species were clearly more sensitive than other species to the fungicide malachite
      green. Environ Toxicol Chem 2018;37:1980-1989. (c) 2018 SETAC.

PMID- 29572917
TI  - The effects of galectin-3 depletion apheresis on induced skin inflammation in a
      porcine model.
AB  - Galectin-3 (Gal-3), a beta-galactoside-binding lectin that is expressed in
      mammalian cells, is known to modulate several biological functions such as cell
      cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The
      goal of this study was to evaluate the ability of Gal-3 depletion apheresis using
      an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation
      induced by Complete Freund's Adjuvant injection in a skin inflammation porcine
      model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding
      immuno-affinity column reduces plasma Gal-3 levels to below limits of
      quantitative detection, and results in significant decrease in skin inflammation,
      including degree and duration of inflammatory lesions. Human plasma was tested ex
      vivo and found to be efficiently depleted using the anti-Gal-3 affinity column.
      This study demonstrates the potential of Gal-3 depletion apheresis as a
      therapeutic method for inflammation-mediated disease, supporting continued
      research in this area for clinical application.

PMID- 29572918
TI  - Status epilepticus: Role for etiology in determining response to benzodiazepines.
AB  - OBJECTIVE: Clinical factors contributing to benzodiazepine failure in treating
      status epilepticus (SE) include suboptimal dosing and seizure duration. As many
      benzodiazepine-refractory episodes of SE arise from acute etiologies, we sought
      to determine whether etiology impacts SE treatment. METHODS: The potency of
      diazepam to terminate SE induced by lithium-pilocarpine (LiPilo-SE) or kainic
      acid (KA-SE) in 3-week-old rats was studied by video-electroencephalography.
      Synaptic gamma-aminobutyric acid type A receptor (GABAR)-mediated currents were
      recorded from dentate granule cells using voltage-clamp electrophysiology.
      Surface expression of gamma2 subunit-containing GABARs and Kv4.2 potassium
      channels in hippocampal slices was determined using a biotinylation assay.
      Expression of phosphorylated forms of beta2/3 and gamma2 subunits was determined
      using phosphospecific antibodies and Western blotting. RESULTS: Diazepam failed
      to terminate late SE in LiPilo-SE animals but was successful in terminating KA-SE
      of 1- and 3-hour duration. One hour after SE onset, GABAR-mediated synaptic
      inhibition and gamma2 subunit-containing GABAR surface expression were reduced in
      LiPilo-SE animals. These were unchanged in KA-SE animals at 1 and 3 hours.
      Phosphorylation of gamma2 subunit residue S327 was unchanged in both models,
      although GABAR beta3 subunit S408/409 residues were dephosphorylated in the
      LiPilo-SE animals. Kv4.2 potassium channel surface expression was increased in
      LiPilo-SE animals but reduced in KA-SE animals. INTERPRETATION: SE-model
      dependent differences support a novel hypothesis that the development of
      benzodiazepine pharmacoresistance may be etiologically predetermined. Further
      studies are required to investigate the mechanisms that underlie such etiological
      differences during SE and whether etiology-dependent protocols for the treatment
      of SE need to be developed. Ann Neurol 2018;83:830-841.

PMID- 29572920
TI  - Stakes in the eye of the beholder: an international study of learners'
      perceptions within programmatic assessment.
AB  - OBJECTIVES: Within programmatic assessment, the ambition is to simultaneously
      optimise the feedback and the decision-making function of assessment. In this
      approach, individual assessments are intended to be low stakes. In practice,
      however, learners often perceive assessments designed to be low stakes as high
      stakes. In this study, we explored how learners perceive assessment stakes within
      programmatic assessment and which factors influence these perceptions. METHODS:
      Twenty-six learners were interviewed from three different countries and five
      different programmes, ranging from undergraduate to postgraduate medical
      education. The interviews explored learners' experience with and perception of
      assessment stakes. An open and qualitative approach to data gathering and
      analyses inspired by the constructivist grounded theory approach was used to
      analyse the data and reveal underlying mechanisms influencing learners'
      perceptions. RESULTS: Learners' sense of control emerged from the analysis as key
      for understanding learners' perception of assessment stakes. Several design
      factors of the assessment programme provided or hindered learners' opportunities
      to exercise control over the assessment experience, mainly the opportunities to
      influence assessment outcomes, to collect evidence and to improve. Teacher
      learner relationships that were characterised by learners' autonomy and in which
      learners feel safe were important for learners' believed ability to exercise
      control and to use assessment to support their learning. CONCLUSIONS: Knowledge
      of the factors that influence the perception of assessment stakes can help design
      effective assessment programmes in which assessment supports learning. Learners'
      opportunities for agency, a supportive programme structure and the role of the
      teacher are particularly powerful mechanisms to stimulate the learning value of
      programmatic assessment.

PMID- 29572921
TI  - Postoperative urinary retention after pelvic organ prolapse repair: Vaginal
      versus robotic transabdominal approach.
AB  - AIMS: Postoperative urinary retention has been reported in 13-32% of patients
      that undergo pelvic organ prolapse (POP) repair. The purpose of our study was to
      compare rates of urinary retention between transvaginal and robotic
      transabdominal approaches and identify risk factors for postoperative urinary
      retention following POP repair. METHODS: Medical records of patients that
      underwent POP repair were reviewed. Surgeries included transvaginal high
      uterosacral ligament suspension (HUSLS) and robotic-assisted sacral colpopexy
      (RASCP). All patients underwent a retrograde fill voiding trial (RGVT)
      postoperatively. Demographics, comorbidities, preoperative urodynamic findings,
      and surgical procedures were compared between women that passed their RGVT and
      those that did not. RESULTS: Out of 484 patients reviewed, 333 underwent POP
      repair with a transvaginal HUSLS and 151 underwent RASCP. Postoperative urinary
      retention was identified in 128 (26.4%) patients where 113 underwent transvaginal
      HUSLS and 15 underwent RASCP. The odds ratio (OR) of postoperative urinary
      retention following transvaginal HUSLS was 3.26 (CI 1.72-6.18; P < 0.001)
      compared to RASCP. Older age was also a risk factor for postoperative urinary
      retention (OR 1.03, CI 1.01-1.05; P = 0.012). While parity, preoperative post
      void residual (PVR), and rates of concomitant transvaginal anterior/posterior
      repair were significantly higher in patients that developed postoperative urinary
      retention on univariate analysis, these factors did not demonstrate significance
      on multivariate analysis. CONCLUSIONS: Transvaginal HUSLS demonstrates a 3.26 OR
      for postoperative urinary retention compared to the robotic transabdominal
      approach. Older age is also a significant risk factor whereas parity,
      preoperative PVR, and rates of concomitant transvaginal anterior/posterior repair
      were not significant risk factors on multivariate analysis.

PMID- 29572922
TI  - Prognostic role of neutrophil to lymphocyte ratio in advanced melanoma treated
      with anti-programmed death-1 therapy.

PMID- 29572924
TI  - Enhancing swallowing recovery after a stroke by harnessing its bihemispheric
      organization.

PMID- 29572923
TI  - Variation in water disappearance, daily dose, and synovial fluid concentrations
      of tylvalosin and 3-O-acetyltylosin in commerical pigs during five day water
      medication with tylvalosin under field conditions.
AB  - Tylvalosin (TVN) is a water soluble macrolide used in swine production to treat
      enteric, respiratory, and arthritic pathogens. There is limited data on its
      distribution to synovial fluid beyond gavage studies, which do not represent
      field conditions. This study measured water disappearance, TVN concentration in
      the medicated water, daily dose, and concentrations of TVN and 3-O-acetyltylosin
      (3AT) in the synovial fluid and plasma of treated pigs over the administration
      period. The study emphasized understanding variation in tissue TVN concentrations
      within the context of a field setting. Sixty finisher pigs were housed
      individually with individual waterers. Six pigs were randomly allocated to the
      following time points for sample collection: 0, 48, 60, 72, 84, 96, 102, 108,
      114, and 120 hr on medication. TVN was administered daily in the water for 5
      days. Water disappearance and medicated water concentration were measured daily.
      At each time point, six pigs were euthanized and plasma and synovial fluid were
      collected for analysis. Median TVN synovial fluid concentrations ranged between
      <1 ng/ml (hour 0) to 3.6 ng/ml (hour 84). There was substantial variation between
      individual pigs for water disappearance (mean 4.36L and range 0-7.84). Median TVN
      water concentration was 59 ppm (range 38-75 ppm).

PMID- 29572925
TI  - Correlating S100B with disease course in a case of new onset, acquired thrombotic
      thrombocytopenic purpura (TTP): Could this be a new predictive biomarker in TTP?
AB  - Acute thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic
      microangiopathy that if not treated, can have a 90% mortality rate. Clinical
      manifestations of this disease include profound thrombocytopenia, hemolytic
      anemia, and end-organ dysfunction. Neurologic symptoms can occur in 80% of
      patients and range from mild confusion to coma (Scully et al., Br J Haematol
      142:819-826). Here, we present the clinical course of a patient diagnosed with
      new onset acquired TTP who presented with neurologic changes that waxed and waned
      during her disease course. In addition to usual clinical and laboratory markers
      for TTP severity and activity, we also collected and analyzed the protein S100B,
      an astroglial protein studied as a marker for central nervous system injury and
      impairment of the blood-brain barrier. Our hypothesis here is that because TTP
      involves endovascular damage, S100B could function as a biomarker for neurologic
      dysfunction and ultimately, predict disease activity. As illustrated in this
      case, our patient's S100B levels did appear to correlate with TTP disease
      activity and the trajectory of this protein seemed a better predictor of
      cognitive function. Furthermore, increased S100B velocity seemed to be the
      earliest indicator of a refractory TTP disease process requiring more intensive
      plasma exchange (TPE) therapy regimen. Therefore, we would suggest that S100B is
      a promising predictive biomarker of disease activity in guiding the intensity of
      TPE therapy for TTP as well as cognitive function.

PMID- 29572926
TI  - Regional brain volumetry and brain function in severely brain-injured patients.
AB  - OBJECTIVE: The relationship between residual brain tissue in patients with
      disorders of consciousness (DOC) and the clinical condition is unclear. This
      observational study aimed to quantify gray (GM) and white matter (WM) atrophy in
      states of (altered) consciousness. METHODS: Structural T1-weighted magnetic
      resonance images were processed for 102 severely brain-injured and 52 healthy
      subjects. Regional brain volume was quantified for 158 (sub)cortical regions
      using Freesurfer. The relationship between regional brain volume and clinical
      characteristics of patients with DOC and conscious brain-injured patients was
      assessed using a linear mixed-effects model. Classification of patients with
      unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using
      regional volumetric information was performed and compared to classification
      using cerebral glucose uptake from fluorodeoxyglucose positron emission
      tomography. For validation, the T1-based classifier was tested on independent
      datasets. RESULTS: Patients were characterized by smaller regional brain volumes
      than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and
      conscious (GM and WM) patients. Classification was successful (misclassification
      with leave-one-out cross-validation between 2% and 13%) and generalized to the
      independent data set with an area under the receiver operator curve of 79% (95%
      confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM.
      INTERPRETATION: Brain volumetry at the single-subject level reveals that regions
      in the default mode network and subcortical gray matter regions, as well as white
      matter regions involved in long range connectivity, are most important to
      distinguish levels of consciousness. Our findings suggest that changes of brain
      structure provide information in addition to the assessment of functional
      neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853.

PMID- 29572927
TI  - Factors affecting use of word-of-mouth by dental patients.
AB  - OBJECTIVES: Word-of-mouth (WOM) refers to communication among consumers, which
      greatly influences the marketing strategies of dental clinics. This study aimed
      to explore factors that affect use of WOM by dental patients and to analyse their
      pathways. METHODS: The participants were 520 outpatients from four private dental
      clinics. Data were obtained from a survey using self-reported questionnaires,
      which included questions regarding seven latent variables: five exogenous
      variables, including medical service quality (physical environment, customer
      service, patient relationship quality) and individual characteristic variables
      (opinion leader tendency, social hub tendency); and two endogenous variables
      (intention to recommend, WOM experience). Statistical analysis was performed
      using structural equation modelling. RESULTS: Significant associations were found
      in the pathways between relationship quality and intention to recommend,
      intention to recommend and WOM, and opinion leader tendency and WOM (P < 0.001).
      Higher patient relationship quality and higher intention to recommend were
      related to positive WOM, as was higher opinion leader tendency. CONCLUSIONS:
      Improving patient relationship quality can promote positive WOM for dental
      clinics. Strategies are needed to promote a positive perception of dental clinics
      by effectively responding to the views of patients with strong opinion leader
      tendencies.

PMID- 29572928
TI  - A novel, trauma-informed physical examination curriculum.

PMID- 29572929
TI  - Multiple genetic variations in sodium channel subunits in a case of sudden infant
      death syndrome.
AB  - BACKGROUND: Dysfunction of NaV 1.5 encoded by SCN5A accounts for approximately
      half of the channelopathic SIDS cases. We investigated the functional effect of
      two gene variants identified in the same patient, one in SCN5A and one in SCN1Bb.
      The aim of the study was to risk stratify the proband's family. METHODS: The
      family was referred for cardiovascular genetic evaluation to assess familial risk
      of cardiac disease. Functional analysis of the identified variants was performed
      with patch-clamp electrophysiology in HEK293 cells. RESULTS: A 16-month-old
      healthy boy died suddenly in the context of nonspecific illness and possible
      fever. Postmortem genetic testing revealed variants in the SCN5A and SCN1Bb
      genes. The proband's father carries the same variants but is asymptomatic.
      Electrophysiological analysis of the NaV 1.5_1281X truncation revealed complete
      loss-of-function of the channel. Coexpression of NaV 1.5 with NaV beta1b
      significantly increased INa density when compared to NaV 1.5 alone. The NaV
      beta1b _V268I variant abolished this INa density increase. Moreover, it shifted
      the activation curve toward more depolarized potentials. CONCLUSIONS: Genetic
      variation of both sodium channel and its modifiers may contribute to sudden
      unexplained death in childhood. However, the asymptomatic father suggests that
      genetic variation of these genes is not sufficient to cause sudden death or
      clinically detectable SCN5A phenotypes.

PMID- 29572930
TI  - Successful treatment of extramammary Paget's disease with S-1 and docetaxel
      combination chemotherapy.

PMID- 29572931
TI  - Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis.
AB  - We performed a genome-wide association study in 1,194 controls and 150 patients
      with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n = 96) or anti-leucine-rich
      glioma-inactivated1 (anti-LGI1, n = 54) autoimmune encephalitis. Anti-LGI1
      encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs)
      in the HLA-II region (leading SNP rs2858870 p = 1.22 * 10-17 , OR = 13.66 [7.50
      24.87]). Potential associations, below genome-wide significance, were found with
      rs72961463 close to the doublecortin-like kinase 2 gene (DCLK2) and rs62110161 in
      a cluster of zinc-finger genes. HLA allele imputation identified association of
      anti-LGI1 encephalitis with HLA-II haplotypes encompassing DRB1*07:01, DQA1*02:01
      and DQB1*02:02 (p < 2.2 * 10-16 ) and anti-NMDAR encephalitis with HLA-I allele
      B*07:02 (p = 0.039). No shared genetic risk factors between encephalitides were
      identified. Ann Neurol 2018;83:863-869.

PMID- 29572932
TI  - Development of an institutional assessment framework.

PMID- 29572933
TI  - Telangiectatic osteosarcoma and renal adenocarcinoma in an Oscar (Astronotus
      ocellatus, Agassiz): Diagnostic imaging and immunohistochemical study.

PMID- 29572934
TI  - Feedforward neural control of toe walking in humans.
AB  - KEY POINTS: Activation of ankle muscles at ground contact during toe walking is
      unaltered when sensory feedback is blocked or the ground is suddenly dropped.
      Responses in the soleus muscle to transcranial magnetic stimulation, but not
      peripheral nerve stimulation, are facilitated at ground contact during toe
      walking. We argue that toe walking is supported by feedforward control at ground
      contact. ABSTRACT: Toe walking requires careful control of the ankle muscles in
      order to absorb the impact of ground contact and maintain a stable position of
      the joint. The present study aimed to clarify the peripheral and central neural
      mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h-1 ).
      Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and
      gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and
      central contributions to the EMG activity were assessed by afferent blockade, H
      reflex testing, transcranial magnetic brain stimulation (TMS) and sudden
      unloading of the planter flexor muscle-tendon complex. Sol EMG activity started
      prior to ground contact and remained high throughout stance. TA EMG activity,
      which is normally seen around ground contact during heel strike walking, was
      absent. Although stretch of the Achilles tendon-muscle complex was observed after
      ground contact, this was not associated with lengthening of the ankle plantar
      flexor muscle fascicles. Sol EMG around ground contact was not affected by
      ischaemic blockade of large-diameter sensory afferents, or the sudden removal of
      ground support shortly after toe contact. Soleus motor-evoked potentials elicited
      by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes
      were not. These findings indicate that at the crucial time of ankle stabilization
      following ground contact, toe walking is governed by centrally mediated motor
      drive rather than sensory driven reflex mechanisms. These findings have
      implications for our understanding of the control of human gait during voluntary
      toe walking.

PMID- 29572936
TI  - Long-term outcomes of posterior chamber phakic intraocular lens implantation in
      keratoconus.
AB  - BACKGROUND: In this retrospective observational case series study, the aim was to
      evaluate the long-term safety, efficacy, stability and predictability of
      posterior chamber phakic intraocular lens (pIOL) implantation to correct myopia
      and myopic astigmatism associated with keratoconus. METHODS: Uncorrected distance
      visual acuity (UDVA), best spectacle-corrected distance visual acuity (BSCDVA),
      refraction and adverse effects were evaluated in 23 keratoconic eyes of 13
      patients after five years with Visian ICMV4 pIOL (STAAR Surgical). RESULTS: The
      mean pre-operative spherical equivalent and cylinder changed from -5.35 +/- 2.82
      D and -3.14 +/- 1.58 D to -0.78 +/- 1.31 D and -1.56 +/- 1.53 D, respectively,
      five years post-operatively. Before the surgery the mean Snellen decimal BSCDVA
      was 0.60 +/- 0.20. The mean UDVA and BSCDVA changed to 0.74 +/- 0.22 and 0.88 +/-
      0.16, respectively. A total of 82.5 per cent of eyes achieved 6/12 or better UDVA
      post-operatively. The mean safety and efficacy indices were respectively, 1.47 +/
      0.32 and 1.24 +/- 0.34. No eye lost a line of visual acuity and 19 eyes gained
      one or more lines. An endothelial cell loss of 7.88 per cent occurred. No
      significant changes were seen in intraocular pressure, steep, flat and mean
      keratometry. The crystalline lens was clear. CONCLUSION: The clinical outcomes of
      the current study demonstrate the safety, efficacy and predictability of the
      implantable collamer lens (toric and non-toric) in the correction of myopia and
      myopic astigmatism associated with keratoconus. The patients' refractions
      achieved early stability and remained stable during the course of the study.

PMID- 29572935
TI  - Effect of interleukin-1beta on occludin mRNA expression in the duodenal and
      colonic mucosa of dogs with inflammatory bowel disease.
AB  - BACKGROUND: Mucosal imbalance of interleukin (IL)-1beta and IL-1 receptor
      antagonist (Ra) has been reported in the duodenal mucosa of dogs with
      inflammatory bowel disease (IBD). However, the imbalance in the colonic mucosa
      and its role in duodenitis and colitis in IBD of dogs remain unclear. OBJECTIVES:
      To measure the expression of IL-1beta and IL-1Ra proteins in the colonic mucosa
      of dogs with IBD, and to determine the effect of IL-1beta on expression of
      occludin (ocln) mRNA, a tight junction component, in the duodenal and colonic
      mucosa of dogs with IBD. ANIMALS: Twelve dogs with IBD and 6 healthy dogs.
      METHODS: IL-1beta and IL-1 Ra proteins in the colonic mucosa were quantified by
      ELISA in 7 of the 12 dogs with IBD. Expression of ocln mRNA in the duodenal and
      colonic mucosa was examined in the 12 dogs by real-time PCR. RESULTS: The ratio
      of IL-1beta to IL-1Ra in the colonic mucosa was significantly higher in dogs with
      IBD than in healthy dogs. The ex vivo experiment determined that IL-1beta
      suppressed expression of ocln mRNA in the colonic mucosa, but not in the duodenal
      mucosa, of healthy dogs. Expression of ocln mRNA in the colonic mucosa, but not
      in the duodenal mucosa, was significantly lower in dogs with IBD than in healthy
      dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: A relative increase in IL-1beta may
      attenuate ocln expression, leading to intestinal barrier dysfunction and
      promotion of intestinal inflammation in the colonic mucosa, but not in the
      duodenal mucosa, of dogs with IBD.

PMID- 29572937
TI  - Suitability of oral administration of monosodium phosphate, disodium phosphate,
      and magnesium phosphate for the rapid correction of hypophosphatemia in cattle.
AB  - BACKGROUND: Hypophosphatemia is commonly associated with disease and decreased
      productivity in dairy cows particularly in early lactation. Oral supplementation
      with phosphate salts is recognized as suitable for the rapid correction of
      hypophosphatemia. Little information is available about the differences in
      efficacy between salts used for oral phosphorus supplementation. OBJECTIVES:
      Comparison of efficacy of oral administration of NaH2 PO4 , Na2 HPO4 , and MgHPO4
      in treating hypophosphatemia in cattle. ANIMALS: 12 healthy dairy cows in the
      fourth week of lactation in their second to fifth lactation. METHODS: Randomized
      clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham
      treatment and were afterwards assigned to 1 of 3 treatments-NaH2 PO4 , Na2 HPO4 ,
      or MgHPO4 (each provided the equivalent of 60 g of phosphorus). Blood samples
      were obtained immediately before and repeatedly after treatment. RESULTS:
      Treatment with NaH2 PO4 and Na2 HPO4 resulted in rapid and sustained increases of
      plasma phosphate concentrations ([Pi]). Significant effects were apparent within
      1 hour (NaH2 PO4 : P = .0044; Na2 HPO4 : P = .0077). Peak increments of plasma
      [Pi] of 5.33 mg/dL [5.26-5.36] and 4.30 mg/dL [3.59-4.68] (median and
      interquartile range) were reached after 7 and 6 hours in animals treated with
      NaPH2 PO4 and Na2 HPO4 , respectively, whereas treatment with MgHPO4 led to peak
      increments 14 hours after treatment (3.19 mg/dL [2.11-4.04]). CONCLUSIONS AND
      CLINICAL IMPORTANCE: NaH2 PO4 and Na2 HPO4 are suitable to rapidly correct
      hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO4
      cannot be recommended for this purpose. Despite important differences in
      solubility of NaH2 PO4 and Na2 HPO4 only small plasma [Pi] differences were
      observed after treatment.

PMID- 29572938
TI  - Prognostic value of echocardiographic indices of left atrial morphology and
      function in dogs with myxomatous mitral valve disease.
AB  - BACKGROUND: The prognostic relevance of left atrial (LA) morphological and
      functional variables, including those derived from speckle tracking
      echocardiography (STE), has been little investigated in veterinary medicine.
      OBJECTIVES: To assess the prognostic value of several echocardiographic
      variables, with a focus on LA morphological and functional variables in dogs with
      myxomatous mitral valve disease (MMVD). ANIMALS: One-hundred and fifteen dogs of
      different breeds with MMVD. METHODS: Prospective cohort study. Conventional
      morphologic and echo-Doppler variables, LA areas and volumes, and STE-based LA
      strain analysis were performed in all dogs. A survival analysis was performed to
      test for the best echocardiographic predictors of cardiac-related death. RESULTS:
      Most of the tested variables, including all LA STE-derived variables were
      univariate predictors of cardiac death in Cox proportional hazard analysis.
      Because of strong correlation between many variables, only left atrium to aorta
      ratio (LA/Ao > 1.7), mitral valve E wave velocity (MV E vel > 1.3 m/s), LA
      maximal volume (LAVmax > 3.53 mL/kg), peak atrial longitudinal strain (PALS <
      30%), and contraction strain index (CSI per 1% increase) were entered in the
      univariate analysis, and all were predictors of cardiac death. However, only the
      MV E vel (hazard ratio [HR], 4.45; confidence interval [CI], 1.76-11.24; P <
      .001) and LAVmax (HR, 2.32; CI, 1.10-4.89; P = .024) remained statistically
      significant in the multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE:
      The assessment of LA dimension and function provides useful prognostic
      information in dogs with MMVD. Considering all the LA variables, LAVmax appears
      the strongest predictor of cardiac death, being superior to LA/Ao and STE-derived
      variables.

PMID- 29572939
TI  - Computed tomographic appearance of abdominal lymph nodes in healthy cats.
AB  - BACKGROUND: Computed tomography (CT) is commonly used in veterinary medicine and
      plays an important role in disease identification and cancer staging.
      Identification of abnormal abdominal lymph nodes is important for clinical,
      therapeutic, and prognostic decision making. No published study describes the CT
      appearance of abdominal lymph nodes in healthy cats. HYPOTHESIS/OBJECTIVES: All
      abdominal lymph centers will be identified on CT with the majority of lymph nodes
      being elongated and homogenously contrast enhancing. ANIMALS: Sixteen healthy
      cats without clinical or biochemical evidence of disease. METHODS: Precontrast
      and postcontrast CT images of sedated healthy cats were used to identify the
      presence and descriptive characteristics of intra-abdominal lymph nodes. These
      assessments then were compared with patient characteristics to identify possible
      correlations. RESULTS: Abdominal lymph nodes were readily identified on CT with
      caudal mesenteric, colic, hepatic, inguinal, and pancreaticoduodenal lymph nodes
      identified in 16/16 cats. Lymph node size and shape varied among lymph centers
      with nearly all lymph nodes homogeneously contrast enhancing in 515/525.
      Significant negative correlations were identified between age and length (P =
      .0166) and width (P = .0387) of abdominal lymph nodes as well as age and number
      of sacral lymph nodes (P = .0493). Intranodal fat was present in 18/525 lymph
      nodes. CONCLUSIONS AND CLINICAL IMPORTANCE: CT readily permitted identification
      and characterization of feline abdominal lymph nodes. This study provides
      subjective and objective data on the CT characteristics of abdominal lymph nodes
      in 16 healthy cats, with younger cats having larger abdominal lymph nodes and a
      higher number of sacral lymph nodes.

PMID- 29572940
TI  - Massive hemorrhage: A rare complication of rapidly involuting congenital
      hemangioma.
AB  - Rapidly involuting congenital hemangioma is a subtype of congenital hemangioma.
      Ulceration and bleeding are rarely reported in rapidly involuting congenital
      hemangioma, with only four cases reported in the literature to our knowledge. We
      describe a case of a newborn girl who presented with rapidly involuting
      congenital hemangioma complicated by ulceration and severe bleeding and discuss
      treatment.

PMID- 29572941
TI  - Detection and characterization of a rhabdovirus causing mortality in black
      bullhead catfish, Ameiurus melas.
AB  - This study fully describes a severe disease outbreak occurred in 2016 in black
      bullhead catfish farmed in Italy. Affected fish showed nervous clinical signs as
      well as emaciations and haemorrhagic petechiae on the skin at the fin bases,
      abdomen and gills. Viral isolation in cell culture allowed the subsequent
      identification of a rhabdovirus, tentatively named ictalurid rhabdovirus (IcRV),
      through electron microscopy, immunofluorescence and whole genome sequencing
      (WGS). The newly isolated virus, together with 14 additional viral strains stored
      in our repository and detected during similar mortality episodes in the period
      1993-2016, was phylogenetically analysed on the basis of the nucleoprotein and
      the glycoprotein nucleotide and amino acid sequences. The genetic distances among
      Italian IcRV strains were also estimated. Our results show that all the IcRV
      strains belong to the genus Sprivivirus and are closely related to the tench
      rhabdovirus (TenRV). Italian catfish production is constantly decreasing, mainly
      due to viral infections, which include the newly characterized IcRV. Data
      presented in this work will assist to investigate the molecular epidemiology and
      the diffusive dynamics of this virus and to develop adequate surveillance
      activities.

PMID- 29572942
TI  - Sonographic features of peritoneal lymphomatosis in 4 cats.
AB  - BACKGROUND: The metastatic spread of feline lymphoma to the peritoneum
      ("lymphomatosis") has been rarely reported in the literature. The sonographic
      features specific to this rare disease manifestation have not been described and
      have important treatment and prognostic considerations prompting definitive
      diagnosis. OBJECTIVES: To describe the ultrasonic features of feline peritoneal
      lymphomatosis. ANIMALS: Four cats with alimentary lymphoma and peritoneal
      metastasis confirmed using cytology, histology, or both. RESULTS: The sonographic
      features described include either a nonobstructive, focally diffuse, and
      circumferential intestinal mass, or an eccentric, focally diffuse, gastric mass.
      The intestinal and gastric lesions exhibited hypo-to-anechoic transmural wall
      thickening with loss of wall layering in association with discrete-to-coalescing
      plaques or sheets of thickened, hypoechoic tissue throughout the mesentery or
      omenta. All cases exhibited only small volumes of anechoic free peritoneal fluid.
      Three of the 4 cats also had multiple small hypoechoic nodular foci on the
      parietal and/or visceral peritoneal surfaces. Two cats had bilateral renomegaly
      because of lymphoma invasion (2/4) and 1 cat had local lymphadenopathy secondary
      to lymphoma invasion (1/4). CONCLUSIONS AND CLINICAL IMPORTANCE: Peritoneal
      lymphomatosis is a rare manifestation of lymphoma metastasis and to date appears
      to be associated specifically with B-cell alimentary lymphoma.

PMID- 29572943
TI  - Urogenital anomalies and urinary incontinence in an English Cocker Spaniel dog
      with XX sex reversal.
AB  - A 3-year-old dog weighing 8 kg was referred with a disorder of sexual development
      and persistent urinary incontinence before and after gonadohysterectomy performed
      at a local animal hospital. Histopathological examination disclosed hypoplasia of
      the testes, epididymis, pampiniform plexus, and uterus. On ultrasonography, an
      anomalous structure containing anechoic fluid was identified in the region dorsal
      to the urinary bladder. An anomalous communication between the proximal urethra
      and the remnant uterus and vagina was found on retrograde urethrography under
      fluoroscopy. Reflux of contrast medium into the anomalous structure, suspected to
      be the uterus and cranial vagina, from the urethra was detected. Computed
      tomography identified the anomalous structure between the rectum and urethra. The
      anomalous structure was removed via laparotomy and the urinary incontinence
      resolved. The diagnosis of XX sex reversal with a developmental anomaly of the
      genitourinary tract was made on the basis of laparotomy findings and cytogenetic
      and SRY gene analyses.

PMID- 29572944
TI  - Kinetic and kinematic follow-up gait analysis in Doberman Pinschers with cervical
      spondylomyelopathy treated medically and surgically.
AB  - BACKGROUND: The efficacy of treatment of dogs with cervical spondylomyelopathy
      (CSM) is commonly based on the owner's and clinician's perception of the gait,
      which is highly subjective and suffers from observer bias. HYPOTHESIS/OBJECTIVES:
      To compare selected kinetic and kinematic parameters before and after treatments
      and to correlate the findings of gait analysis to clinical outcome. ANIMALS:
      Eight Doberman Pinschers with CSM confirmed by magnetic resonsance imaging.
      METHODS: Patients were prospectively studied and treated with either medical
      management (n = 5) or surgery (n = 3). Force plate analysis and 3-D kinematic
      motion capture were performed at initial presentation and approximately 8 weeks
      later. Force plate parameters evaluated included peak vertical force (PVF).
      Kinematic parameters measured included number of pelvic limb strides, stifle
      flexion and extension, maximum and minimum thoracic limb distance, truncal sway,
      and thoracic limb stride duration. RESULTS: Kinematic analysis showed that
      deviation of the spine to the right (truncal sway) was significantly smaller (P <
      .001) and the degree of right stifle flexion was significantly larger (P = .029)
      after treatment. Force plate analysis indicated that PVF was significantly
      different after treatment (P = .049) and the difference of the PVF also was
      significantly larger (P = .027). However, no correlation was found with either
      method of gait analysis and clinical recovery. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Kinetic and kinematic gait analysis were able to detect differences
      in dogs with CSM before and after treatment. A correlation of gait analysis to
      clinical improvement could not be determined.

PMID- 29572945
TI  - Structural basis of noncanonical polyphenol oxidase activity in DLL-II: A lectin
      from Dolichos lablab.
AB  - Lectins known to possess an additional enzymatic function are called leczymes.
      Previous studies reported a unique polyphenol oxidase (PPO) activity in DLL-II-a
      leczyme from Dolichos lablab. DLL-II shares a high sequence and structural
      homology with DBL-another leczyme from Dolichos biflorus. Incidentally, DBL
      possesses lipoxygenase activity, but not the PPO activity. Legume lectins usually
      possess two metal-binding sites A and B. Although these sites are conserved in
      both DBL and DLL-II, site A in DLL-II is occupied by Mn2+ and site B by Ca2+ . In
      contrast, DLL-II binds Cu2+ and Ca2+ at sites A and B, respectively. Here,
      investigating the structural basis of PPO activity in DLL-II, we find that the
      PPO activity is only dependent on Cu2+ , but not Ca2+ ; and the lectin activity
      requires only Ca2+ . Further, our analysis suggests that an alternative mechanism
      of PPO reaction may be operative in DLL-II, which involves a mononuclear Cu2+
      metal center; this is in contrast to the bi-nuclear Cu2+ metal center commonly
      observed in all PPOs. Importantly, structural and computational approaches
      employed here, we hypothesize possible PPO binding sites and the corresponding
      migration channels for accessing the active site.

PMID- 29572946
TI  - Prospective long-term evaluation of parenteral hydroxocobalamin supplementation
      in juvenile beagles with selective intestinal cobalamin malabsorption (Imerslund
      Grasbeck syndrome).
AB  - BACKGROUND: Prospective studies on maintenance treatment for Beagles with
      hereditary selective cobalamin (Cbl) malabsorption (Imerslund-Grasbeck syndrome,
      IGS) are lacking. In our experience, measurement of methylmalonic acid (MMA), a
      Cbl-dependent metabolite, seems more helpful to monitor Cbl status as compared
      with serum Cbl concentrations. OBJECTIVES: To evaluate a standardized Cbl
      supplementation scheme in Beagles with IGS. We hypothesized that a single
      parenteral dose of 1 mg hydroxocobalamin (OH-Cbl) would maintain clinical and
      metabolic remission for up to 2 months. ANIMALS: Six client-owned juvenile
      Beagles with genetically confirmed IGS and 28 healthy control dogs. METHODS:
      Prospective study. Monthly IM OH-Cbl (1 mg) supplementation was done over a
      median of 9 months (range, 6-13) in 6 dogs, followed by bimonthly (every 2
      months) injections in 5 dogs over a median of 6 months (range, 3-10). Health
      status was assessed by routine clinical examinations at injection time points and
      owner observations. Voided urine samples were collected immediately before OH-Cbl
      injections for measurement of MMA-to-creatinine concentrations using a gas-liquid
      chromatography-tandem mass spectrometry (GC-MS) method. RESULTS: All dogs were
      clinically healthy while receiving monthly and bimonthly OH-Cbl supplementation.
      Urinary MMA results in healthy dogs ranged from 1.3 to 76.5 mmol/mol creatinine
      (median, 2.9). Median urinary MMA concentrations did not differ between dogs with
      IGS receiving monthly (n = 49; 5.3 mmol/mol creatinine; range, 2.3-50.4) and
      bimonthly (n = 31; 5.3 mmol/mol creatinine; range, 1.6-50) injections.
      CONCLUSIONS AND CLINICAL IMPORTANCE: A maintenance parenteral dose of 1 mg OH-Cbl
      monthly or bimonthly appears adequate in Beagles with IGS monitored by metabolic
      testing.

PMID- 29572947
TI  - Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and
      laminitis.
AB  - BACKGROUND: Metabolomics, the study of small-molecule metabolites, has increased
      understanding of human metabolic diseases, but has not been used to study equine
      metabolic syndrome (EMS). OBJECTIVES: (1) To examine the serum metabolome of
      Welsh Ponies with and without insulin dysregulation before and during an oral
      sugar test (OST). (2) To identify differences in metabolites in ponies with
      insulin dysregulation, obesity, or history of laminitis. ANIMALS: Twenty Welsh
      Ponies (mean +/- SD; 13.8 +/- 9.0 years) classified as non-insulin dysregulated
      [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin >
      60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or
      nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n
      = 11). METHODS: Case-control study. Metabolomic analysis was performed on serum
      obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were
      analyzed with multivariable mixed linear models with significance set at P <=
      .05. RESULTS: Metabolomic analysis of 646 metabolites (506 known) detected
      significant metabolite differences. At baseline, 55 metabolites (insulin
      response), 91 metabolites (obesity status), and 136 metabolites (laminitis
      history) were different. At 75 minutes, 51 metabolites (insulin response), 102
      metabolites (obesity status), and 124 metabolites (laminitis history) were
      different. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of metabolomics could have
      diagnostic utility for early detection of EMS and provide new knowledge regarding
      the pathophysiology of metabolic perturbations associated with this condition
      that might lead to improved clinical management.

PMID- 29572948
TI  - Longitudinal Change of Clinical and Biological Measures in Early Parkinson's
      Disease: Parkinson's Progression Markers Initiative Cohort.
AB  - OBJECTIVE: The objective of this study was to assess longitudinal change in
      clinical and dopamine transporter imaging outcomes in early, untreated PD.
      METHODS: We describe 5-year longitudinal change of the MDS-UPDRS and other
      clinical measures using results from the Parkinson's Progression Markers
      Initiative, a longitudinal cohort study of early Parkinson's disease (PD)
      participants untreated at baseline. We also provide data on the longitudinal
      change in dopamine transporter 123-I Ioflupane striatal binding and correlation
      between the 2 measures. RESULTS: A total of 423 PD participants were recruited,
      and 358 remain in the study at year 5. Baseline MDS-UPDRS total score was 32.4
      (standard deviation 13.1), and the average annual change (assessed medications
      OFF for the treated participants) was 7.45 (11.6), 3.11 (11.7), 4(11.9), 4.7
      (11.1), and 1.74(11.9) for years 1, 2, 3, 4, and 5, respectively (P < .0001 for
      the change over time), with a steeper change in year 1. Dopaminergic therapy had
      a significant effect on the change of MDS-UPDRS. There was a significant
      longitudinal change in dopamine transporter binding in all striatal regions (P <
      .001). There was a significant but weak correlation between MDS-UPDRS and
      dopamine transporter binding at baseline and years 1, 2, and 4, but no
      correlation between the rate of change of the 2 variables. CONCLUSIONS: We
      present 5-year longitudinal data on the change of the MDS-UPDRS and other
      clinical and dopamine transporter imaging outcome measures in early PD. These
      data can be used for sample size estimates for interventional studies in the de
      novo PD population. (c) 2018 The Authors. Movement Disorders published by Wiley
      Periodicals, Inc. on behalf of International Parkinson and Movement Disorder
      Society.

PMID- 29572950
TI  - Failure of CT angiogram to detect an ascending aortic dissection.

PMID- 29572949
TI  - Detection and seroprevalence of morbillivirus and other paramyxoviruses in
      geriatric cats with and without evidence of azotemic chronic kidney disease.
AB  - BACKGROUND: Feline morbillivirus (FeMV) is associated with the presence of tubulo
      interstitial nephritis (TIN) in cats, however the seroprevalence of FeMV in the
      UK and the association between the presence of FeMV and renal azotemia is unknown
      HYPOTHESIS/OBJECTIVES: To identify whether paramyxoviruses are present in urine
      samples of geriatric cats and to develop an assay to assess FeMV seroprevalence.
      To investigate the relationship between both urinary paramyxovirus (including
      FeMV) excretion and FeMV seroprevalence and azotemic chronic kidney disease
      (CKD). ANIMALS: Seventy-nine cats (40 for FeMV detection; 72 for seroprevalence).
      METHODS: Retrospective cross-sectional, case control study. Viral RNA was
      extracted from urine for RT-PCR. PCR products were sequenced for virus
      identification and comparison. The FeMV N protein gene was cloned and partially
      purified for use as an antigen to screen cat sera for anti-FeMV antibodies by
      Western Blot. RESULTS: Feline morbillivirus RNA from five distinct
      morbilliviruses were identified. Detection was not significantly different
      between azotemic CKD (1/16) and nonazotemic groups (4/24; P = .36). Three
      distinct, non-FeMV paramyxoviruses were present in the nonazotemic group but
      their absence from the azotemic group was not statistically significant (P =
      .15). 6/14 (43%) azotemic cats and 40/55 (73%) nonazotemic cats were seropositive
      (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: Feline morbillivirus was detected
      in cats in the UK for the First time. However, there was no association between
      virus prevalence or seropositivity and azotemic CKD. These data do not support
      the hypothesis that FeMV infection is associated with the development of azotemic
      CKD in cats in the UK.

PMID- 29572952
TI  - A Genealogy of Animal Diseases and Social Anthropology (1870-2000).
AB  - Culling, vaccinating, and monitoring animals are the three main techniques used
      in contemporary veterinary public health to manage animal diseases that can be
      transmitted to humans. Each technique is underpinned by different ontological
      understandings of how microbes figure in relations between humans and animals.
      Therefore, animal diseases are not only a question for an applied anthropology
      but also involve the theoretical core of the discipline: that is, understanding
      how social causality emerges out of physical causality. To defend this argument,
      the article describes what Herbert Spencer wrote about foot-and-mouth disease;
      what William Robertson Smith thought about sacrifice in the context of bovine
      tuberculosis; how Emile Durkheim took vaccination for smallpox as a metaphor for
      the pathologies of the social; and what Claude Levi-Strauss wrote about mad cow
      disease. The conceptions of the social in the writing of these four authors are
      analyzed through their understanding of the risk of transmission of animal
      diseases to humans, moving from prevention to precaution to preparedness.

PMID- 29572951
TI  - Effect of heat treatment on 4'-O-methylpyridoxine (MPN) content in Ginkgo biloba
      seed extract solution.
AB  - BACKGROUND: A vitamin B6 derivative, 4'-O-methylpyridoxine (MPN), is responsible
      for food poisoning by Ginkgo biloba seeds. In this study, we investigate the
      content of pyridoxine and MPN in MPN standard solution and G. biloba seed extract
      solution upon heat treatment in order to evaluate the reduction of toxic
      components in G. biloba seed by such treatment. RESULTS: Heat treatment was
      conducted at 90-150  degrees C for 0-60 min, and all samples were adjusted to the
      same concentration of 1 g L-1 . The MPN content decreased to 994.92-563.69 mg kg
      1 for MPN standard solution and to 371.56-76.84 mg kg-1 for G. biloba seed
      extract solution, and in both cases decreased even further with increasing heat
      treatment time. However, in all samples, except for the 90  degrees C heat
      treatment group, the pyridoxine content in MPN standard solution increased with
      increasing heat temperature and time; in addition, the extract solution showed a
      similar tendency. This may be the result of thermal degradation of MPN into
      pyridoxine. CONCLUSION: We can expect to improve the utilization of functional
      food materials by applying suitable heat treatment conditions and decreasing the
      MPN content of the G. biloba seed. (c) 2018 Society of Chemical Industry.

PMID- 29572953
TI  - A novel mouse model of human prostate cancer to study intraprostatic tumor growth
      and the development of lymph node metastases.
AB  - BACKGROUND: In this study, we aimed to establish a versatile in vivo model of
      prostate cancer, which adequately mimics intraprostatic tumor growth, and the
      natural routes of metastatic spread. In addition, we analyzed the capability of
      high-resolution ultrasonography (hrUS), in vivo micro-CT (MUCT), and 9.4T MRI to
      monitor tumor growth and the development of lymph node metastases. METHODS: A
      total of 5 * 105 VCaP cells or 5 * 105 cells of LuCaP136- or LuCaP147 spheroids
      were injected into the prostate of male CB17-SCID mice (n = 8 for each cell
      type). During 12 weeks of follow-up, orthotopic tumor growth, and metastatic
      spread were monitored by repetitive serum-PSA measurements and imaging studies
      including hrUS, MUCT, and 9.4T MRI. At autopsy, primary tumors and metastases
      were harvested and examined by histology and immunohistochemistry (CK5, CK8,
      AMACR, AR, Ki67, ERG, and PSA). From imaging results and PSA-measurements, tumor
      volume doubling time, tumor-specific growth rate, and PSA-density were
      calculated. RESULTS: All 24 mice developed orthotopic tumors. The tumor growth
      could be reliably monitored by a combination of hrUS, MUCT, MRI, and serum-PSA
      measurements. In most animals, lymph node metastases could be detected after 12
      weeks, which could also be well visualized by hrUS, and MRI. Immunohistochemistry
      showed positive signals for CK8, AMACR, and AR in all xenograft types. CK5 was
      negative in VCaP- and focally positive in LuCaP136- and LuCaP147-xenografts. ERG
      was positive in VCaP- and negative in LuCaP136- and LuCaP147-xenografts. Tumor
      volume doubling times and tumor-specific growth rates were 21.2 days and 3.9
      %/day for VCaP-, 27.6 days and 3.1 %/day for LuCaP136- and 16.2 days and 4.5
      %/day for LuCaP147-xenografts, respectively. PSA-densities were 433.9 ng/mL per
      milliliter tumor for VCaP-, 6.5 ng/mL per milliliter tumor for LuCaP136-, and
      11.2 ng/mL per milliliter tumor for LuCaP147-xenografts. CONCLUSIONS: By using
      different monolayer and 3D spheroid cell cultures in an orthotopic xenograft
      model, we established an innovative, versatile in vivo model of prostate cancer,
      which enables the study of both intraprostatic tumor growth as well as metastatic
      spread to regional lymph nodes. HrUS and MRI are feasible tools to monitor tumor
      growth and the development of lymph node metastases while these cannot be
      visualized by MUCT.

PMID- 29572954
TI  - Water requirements of canine athletes during multi-day exercise.
AB  - BACKGROUND: Exercise increases water requirements, but there is little
      information regarding water loss in dogs performing multi-day exercise
      OBJECTIVES: Quantify the daily water turnover of working dogs during multi-day
      exercise and establish the suitability of SC administration of tracer to
      determine water turnover. ANIMALS: Fifteen privately owned Labrador retrievers
      trained for explosive detection duties and 16 privately owned Alaskan Huskies
      conditioned for mid-distance racing. METHODS: All dogs received 0.3 g D2 O/kg
      body weight by IV infusion, gavage, or SC injection before the start of a multi
      day exercise challenge. Explosive detection dogs conducted 5 days of simulated
      off-leash explosive detection activity. Alaskan sled dogs completed a mid
      distance stage race totaling 222 km in 2 days. Total body water (TBW) and daily
      water turnover were calculated using both indicator dilution and elimination
      regression techniques. RESULTS: Total body water (% of body weight) varied from
      60% +/- 8.6% in minimally conditioned Labrador retrievers to 74% +/- 4.5% in
      highly conditioned Labrador retrievers. Daily water turnover was as high as 45%
      of TBW during exercise in cold conditions. There was no effect of sex or speed on
      daily water turnover. There was good agreement between results calculated using
      the indicator dilution approach and those calculated using a semilog linear
      regression approach when indicator isotope was administered IV or SC. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Water requirements are influenced primarily by the
      amount of work done. SC administration of isotope-labeled water offers a simple
      and accurate alternative method for metabolic studies.

PMID- 29572955
TI  - High Imminent Vertebral Fracture Risk in Subjects With COPD With a Prevalent or
      Incident Vertebral Fracture.
AB  - Subjects with chronic obstructive pulmonary disease (COPD) have an increased risk
      of vertebral fractures (VFs); however, VF incidence is largely unknown.
      Therefore, the aim of our study was to determine the incidence of new and/or
      worsening VF in subjects with COPD. Smokers and subjects with COPD (GOLD II-IV)
      from the ECLIPSE study with complete set of chest CT scans (baseline and 1- and 3
      year follow-up) to evaluate vertebrae T1 down to L1 were included. If a VF was
      diagnosed on the last scan, detailed VF assessment of the previous scans was
      performed. VFs were scored according to the method of Genant as mild, moderate,
      or severe. Main outcome measure was the cumulative incidence of new and/or
      worsening VF at subject level, within 1 and 3 years. Of 1239 subjects (mean age
      61 years, 757 males [61%], 999 subjects with COPD), 253 (20.5%) had >=1 prevalent
      VF. The cumulative incidence of VFs was 10.1% within 1 year and 24.0% within 3
      years. After adjustment for age, sex, body mass index (BMI), pack-years, and
      smoking status, prevalence and incidence were similar between smokers and COPD
      GOLD stages. Within 1 year, 29.2% of the subjects with a prevalent VF had an
      incident VF, compared with 5.1% in absence of prevalent VF (hazard ratio [HR] =
      5.1; 95% confidence interval [CI] 3.6-7.4) and 58.5% versus 15.0% within 3 years
      (HR = 3.6; 95% CI 2.9-4.6). The incidence of VF was higher with increasing number
      and severity of prevalent VFs. Among subjects having an incident VF within the
      first year, 57.3% had a subsequent VF within the next 2 years. In this study,
      more than half of the smokers and subjects with COPD with a prevalent VF or an
      incident VF within the first year sustained a subsequent VF within 3 years. The 3
      year risk was even higher in the presence of multiple or severe prevalent VFs.
      (c) 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley
      Periodicals Inc.

PMID- 29572956
TI  - Trends in time-loss injuries during the 2011-2016 South African Rugby Youth
      Weeks.
AB  - Youth rugby is a popular sport in South Africa (SA) with a high injury incidence.
      The annual SA Rugby Youth Week tournaments attract the top age-group players in
      the country providing a sample of players for reliable injury surveillance. The
      aim of the study was to analyze the changes in time-loss injury rates at the SA
      Rugby Youth Week tournaments between 2011 and 2016, differences between age
      groups, and to investigate associated injury risk factors. All confirmed time
      loss injuries at the 4 age-group tournaments (under-13, under-16, and 2 under-18)
      from 2011 to 2016 were recorded. Injury incidence densities (IID) for years,
      tournaments, and injury risk factors were calculated and Poisson regression
      analyses were performed to determine differences. Time-loss injuries (n = 494)
      were reported over 24 240 exposure hours, with an overall IID of 20.4 (18.6-22.2)
      injuries per 1000 player hours. The year 2013 had a significantly lower IID
      compared to 2011. Injury risk decreased with increasing age; under-13 and under
      16 had significantly higher IID compared to under-18 Craven Week. Tackling was
      the phase of play at highest risk, with an IID of 7.4 (6.3-8.5) injuries per 1000
      player hours. Central/peripheral nervous system (CNS/PNS) and, therefore, the
      head/neck were the most commonly occurring injuries/location injured. In
      conclusion, within the SA Rugby tournament structure, the older players had a
      decreased rate of injury. The tackle event was still the phase of play with the
      highest injury incidence regardless of age. This increase in incidence is largely
      due to an increase in CNS/PNS injuries.

PMID- 29572957
TI  - Optometric infection control guidelines assessing patients with methicillin
      resistant Staphylococcus aureus.
AB  - The purpose of this scoping review was to present the state of research regarding
      optometric infection control guidelines for the assessment of patients with
      methicillin-resistant Staphylococcus aureus (MRSA) and to identify any areas
      requiring further research. Twelve articles were carefully chosen for review.
      Data extracted included information regarding appropriate handwashing methods
      (five articles), indications for use of personal protective equipment (one
      article), management of surfaces that come in contact with an MRSA-infected
      person (three articles), recommendations for patient appointment
      scheduling/seating (three articles) and suggestions for staff training (three
      articles). The results of the review demonstrated that there exist many gaps in
      the literature regarding comprehensive optometric-specific infection control
      guidelines. Further research regarding appropriate handwashing methods, equipment
      disinfection techniques, extent and breadth of staff training and indications for
      use of personal protective equipment is required to better understand what
      precautions must be taken in an optometric setting when encountering patients
      with MRSA.

PMID- 29572958
TI  - Pharmacokinetics and efficacy of intravenous famotidine in adult cattle.
AB  - BACKGROUND: Abomasal ulceration is recognized in neonatal and adult cattle, but
      research regarding treatment is limited. Histamine-2 receptor antagonists (H2
      RA), such as famotidine, are used clinically with little evidence-based research
      about efficacy in adult cattle. HYPOTHESIS AND OBJECTIVES: Intravenous famotidine
      administered at 0.4 mg/kg will increase the pH of abomasal outflow digesta
      compared to saline control in adult cattle. The objectives were to assess the
      effect of famotidine, administered as a single dose and as multiple doses, on
      abomasal outflow fluid pH in adult cattle. A third objective was to describe the
      pharmacokinetic parameters of IV famotidine in cattle. ANIMALS: Four clinically
      healthy adult Angus-cross steers previously fitted with duodenal cannulae placed
      orad to the biliary and pancreatic ducts. METHODS: Randomized, 2-way cross-over
      clinical trial. Steers received IV famotidine (0.4 mg/kg) as a single and 3-dose
      regimen (every 8 hours) versus saline control. Blood for analysis of serum
      famotidine concentration was collected intermittently for 12 hours, and abomasal
      outflow fluid pH was measured at intervals for a 24-hour period. After a 34-hour
      washout period, the opposite treatments were administered and the sampling
      repeated. RESULTS: Abomasal outflow fluid pH was higher in steers treated with
      famotidine for up to 4 hours after a single dose but the effect decreased with
      subsequent doses. The median (range) elimination half-life was 3.33 (3.21-3.54)
      hours. CONCLUSIONS AND CLINICAL IMPORTANCE: Famotidine may be useful for
      treatment or prevention of abomasal ulceration in adult cattle, but the duration
      of effect may decrease with time.

PMID- 29572959
TI  - A highly decoupled transmit-receive array design with triangular elements at 7T.
AB  - PURPOSE: Transmit arrays are essential tools for various RF shimming or parallel
      excitation techniques at 7T. Here we present an array design with triangular
      coils to improve diversity in the B1 profiles in the longitudinal (z) direction
      and allow for next-nearest neighbor decoupling. METHODS: Two cylindrical 8
      channel arrays having the same length and diameter, 1 of triangular coils and the
      other of rectangular coils, were constructed and compared in phantom imaging
      experiments using measures of excitation distribution for a variety of RF shim
      settings and geometry factor maps for different accelerations on different
      planes. RESULTS: Coupling between elements was -20 dB or better for all
      triangular coil pairs, but worse than -12 dB for several of the rectangular coil
      pairs. Both coils could produce adequate shims on a central transverse plane, but
      the same shim produced worse results off center for the triangular coil array
      than for the rectangular coil array. Compared to the rectangular coil array, the
      maximum geometry factor for the triangular coil array was reduced by a factor of
      13.1 when using a 2-fold acceleration in the z-direction. CONCLUSION: An array
      design with triangular coils provides effective decoupling mechanisms for nearest
      and next-nearest neighboring elements, as well as diversity in B1 profiles along
      the z-direction, although this also means that individual slices must be shimmed
      separately. This design is well suited for parallel transmit applications while
      also having high receive sensitivity.

PMID- 29572960
TI  - The demosponge Halichondria (Halichondria) panicea (Pallas, 1766) as a novel
      source of biosurfactant-producing bacteria.
AB  - The Mediterranean sponge Halichondria (Halichondria) panicea was explored as a
      novel matrix for the isolation of biosurfactant-producing bacteria. A total of 38
      (out of 56) isolates gave a good response to the employed screening tests (e.g.,
      stable emulsion detection, surface tension measurement, hemolytic activity, and
      blue agar plate assay) and were selected for further analyses. The thin layer
      chromatography revealed a possible glucidic composition of biosurfactants. Most
      promising strains, i.e., those able to produce stable emulsion with percentage
      higher than 30% and yellow spots on TLC plates, were affiliated to the genera
      Pseudovibrio, Acinetobacter, and Bacillus. The biosurfactant production by two
      isolates (i.e., Acinetobacter sp. SpN134 and Pseudovibrio sp. SpE85) was
      evaluated under different culture conditions, in terms of temperature, NaCl
      concentration, and pH. Surface tension reduction ability was more stable than the
      emulsification, and resulted differently influenced by salinity, temperature, and
      pH. Acinetobacter sp. SpN134 resulted particularly efficient and competitive if
      compared with other well-known biosurfactant producers. Data suggest that sponges
      may represent a promising matrix for the isolation of biosurfactant-producing
      bacteria, reinforcing the growing interest towards filter-feeding organisms as
      underexplored sources of specialized bacteria.

PMID- 29572961
TI  - Maintenance of Serum Ionized Calcium During Exercise Attenuates Parathyroid
      Hormone and Bone Resorption Responses.
AB  - Exercise can cause a decrease in serum ionized calcium (iCa) and increases in
      parathyroid hormone (PTH) and bone resorption. We used a novel intravenous iCa
      clamp technique to determine whether preventing a decline in serum iCa during
      exercise prevents increases in PTH and carboxy-terminal collagen crosslinks
      (CTX). Eleven cycling-trained men (aged 18 to 45 years) underwent two identical
      60-min cycling bouts with infusion of Ca gluconate or saline. Blood sampling for
      iCa, total calcium (tCa), PTH, CTX, and procollagen type 1 amino-terminal
      propeptide (P1NP) occurred before, during, and for 4 hours after exercise;
      results are presented as unadjusted and adjusted for plasma volume shifts
      (denoted with subscript ADJ). iCa decreased during exercise with saline infusion
      (p = 0.01 at 60 min) and this was prevented by Ca infusion (interaction, p <
      0.007); there were abrupt decreases in Ca content (iCaADJ and tCaADJ ) in the
      first 15 min of exercise under both conditions. PTH and CTX were increased at the
      end of exercise (both p < 0.01) on the saline day, and markedly attenuated (-65%
      and -71%; both p < 0.001) by Ca. CTX remained elevated for 4 hours after exercise
      on the saline day (p < 0.001), despite the return of PTH to baseline by 1 hour
      after exercise. P1NP increased in response to exercise (p < 0.001), with no
      difference between conditions, but the increase in P1NPADJ was not significant.
      Results for PTHADJ and CTXADJ were similar to unadjusted results. These findings
      demonstrate that bone resorption is stimulated early in exercise to defend serum
      iCa. Vascular Ca content decreased early in exercise, but neither the reason why
      this occurred, nor the fate of Ca, are known. The results suggest that the
      exercise-induced increase in PTH had an acute catabolic effect on bone. Future
      research should determine whether the increase in PTH generates an anabolic
      response that occurs more than 4 hours after exercise. (c) 2018 American Society
      for Bone and Mineral Research.

PMID- 29572962
TI  - Unique Bond Breaking in Crystalline Phase Change Materials and the Quest for
      Metavalent Bonding.
AB  - Laser-assisted field evaporation is studied in a large number of compounds,
      including amorphous and crystalline phase change materials employing atom probe
      tomography. This study reveals significant differences in field evaporation
      between amorphous and crystalline phase change materials. High probabilities for
      multiple events with more than a single ion detected per laser pulse are only
      found for crystalline phase change materials. The specifics of this unusual field
      evaporation are unlike any other mechanism shown previously to lead to high
      probabilities of multiple events. On the contrary, amorphous phase change
      materials as well as other covalently bonded compounds and metals possess much
      lower probabilities for multiple events. Hence, laser-assisted field evaporation
      in amorphous and crystalline phase change materials reveals striking differences
      in bond rupture. This is indicative for pronounced differences in bonding. These
      findings imply that the bonding mechanism in crystalline phase change materials
      differs substantially from conventional bonding mechanisms such as metallic,
      ionic, and covalent bonding. Instead, the data reported here confirm a recently
      developed conjecture, namely that metavalent bonding is a novel bonding mechanism
      besides those mentioned previously.

PMID- 29572963
TI  - Local treatment for metastatic prostate cancer: A systematic review.
AB  - The potential oncological benefit for radical treatment in the setting of
      oligometastatic prostate cancer has been under investigation and is frequently
      discussed. We carried out a systematic review of English language articles using
      the Medline database (January 2000 to May 2017) to identify studies reporting
      local treatment in men with metastatic prostate cancer at diagnosis. Primary end
      points were oncological outcomes, such as cancer-specific and overall mortality.
      Secondary end-points were non-oncological outcomes, such as complications,
      operating room time, blood loss or length of hospital stay. Two independent
      authors reviewed and extracted all search results. Overall, 18 studies reporting
      on local treatment in metastatic prostate cancer patients were identified (14
      original articles, three brief correspondences and one letter to the editor). All
      of them were retrospective; one partly included prospective data. All studies
      addressed oncological outcomes, 16 compared local treatment with no-local
      treatment and 14 adjusted for confounders using multivariable regression models.
      All but one study concluded a survival benefit for local treatment in the
      metastatic setting. Due to heterogeneity of available data, a representative meta
      analysis could not be carried out. Five studies reported non-oncological
      outcomes. Although local treatment in metastatic prostate cancer appears to be
      feasible, its oncological effect remains unclear due to high susceptibility of
      available studies to significant selection bias.

PMID- 29572964
TI  - Nonnoble-Metal-Based Plasmonic Nanomaterials: Recent Advances and Future
      Perspectives.
AB  - The application scope of plasmonic nanostructures is rapidly expanding to keep
      pace with the ongoing development of various scientific findings and emerging
      technologies. However, most plasmonic nanostructures heavily depend on rare,
      expensive, and extensively studied noble metals such as Au and Ag, with the
      limited choice of elements hindering their broad and practical applications in a
      wide spectral range. Therefore, abundant and inexpensive nonnoble metals have
      attracted attention as new plasmonic nanomaterial components, allowing these
      nonnoble-metal-based materials to be used in areas such as photocatalysis,
      sensing, nanoantennas, metamaterials, and magnetoplasmonics with new
      compositions, structures, and properties. Furthermore, the use of nonnoble metal
      hybrids results in newly emerging or synergistic properties not observed from
      single-metal component systems. Here, the synthetic strategies and recent
      advances in nonnoble-metal-based plasmonic nanostructures comprising Cu, Al, Mg,
      In, Ga, Pb, Ni, Co, Fe, and related hybrids are highlighted, and a discussion and
      perspectives in their synthesis, properties, applications, and challenges are
      presented.

PMID- 29572965
TI  - Nanomaterial-Based Plasmon-Enhanced Infrared Spectroscopy.
AB  - Surface-enhanced infrared absorption (SEIRA) has attracted increasing attention
      due to the potential of infrared spectroscopy in applications such as molecular
      trace sensing of solids, polymers, and proteins, specifically fueled by recent
      substantial developments in infrared plasmonic materials and engineered
      nanostructures. Here, the significant progress achieved in the past decades is
      reviewed, along with the current state of the art of SEIRA. In particular, the
      plasmonic properties of a variety of nanomaterials are discussed (e.g., metals,
      semiconductors, and graphene) along with their use in the design of efficient
      SEIRA configurations. To conclude, perspectives on potential applications,
      including single-molecule detection and in vivo bioassays, are presented.

PMID- 29572966
TI  - Solvent polarity effects on supramolecular chirality of a polyfluorene-thiophene
      copolymer.
AB  - This study demonstrates the supramolecular chirality control of a conjugated
      polymer via solvent polarity. We designed and synthesized a chiral polyfluorene
      thiophene copolymer having two different chiral side chains at the 9-position of
      the fluorene unit. Chiral cyclic and alkyl ethers with different polarities were
      selected as the chiral side chains. The sign of the circular dichroism spectra in
      the visible wavelength region was affected by the solvent system, resulting from
      the change of supramolecular structure. The estimation of the solubility
      parameter revealed that the solubility difference of the side chains contributed
      to the change of the circular dichroism sign, which was also observed in spin
      coated films prepared from good solvents having different polarities.

PMID- 29572967
TI  - In chemico skin sensitization risk assessment of botanical ingredients.
AB  - Skin sensitization risk assessment of botanical ingredients is necessary for
      consumers' protection and occupational hazard identification. There are currently
      very few available alternative methods that can assist in the evaluation of
      complex mixtures. Chemical methods can provide essential information in a timely
      manner and thus help to reduce the need for in vivo testing, and they can
      complement and facilitate targeted in vitro assays. In the present work, the
      applicability of the high-throughput screening with dansyl cysteamine (DCYA)
      method for the systematic evaluation of skin sensitization of complex botanicals
      was explored. Botanical ingredients of four unrelated plant species were obtained
      and tested with the high-throughput fluorescence method at three concentrations.
      To illustrate the minimal matrix effects of the tested extracts on the developed
      method, the least DCYA-reactive extract (Rosa canina) was spiked with known
      sensitizers at different concentrations. The data obtained from the four plant
      extracts and the spiking experiments with known sensitizers, suggest that the
      high-throughput screening-DCYA method can be successfully applied for estimating
      the skin sensitization potential of complex botanical matrices. This is the first
      report of an attempt to develop a versatile in chemico method for the rapid
      detection of reactive skin sensitizers in complex botanical extracts, which could
      complement the battery of existing validated, non-animal methods.

PMID- 29572968
TI  - Implantable Synthetic Immune Niche for Spatiotemporal Modulation of Tumor-Derived
      Immunosuppression and Systemic Antitumor Immunity: Postoperative Immunotherapy.
AB  - The development of biomaterial-based immune niches that can modulate
      immunosuppressive factors in tumor microenvironment (TME) will be a key
      technology for improving current cancer immunotherapy. Here, implantable,
      engineered 3D porous scaffolds are designed to generate synergistic action
      between myeloid-derived suppressor cell (MDSC)-depleting agents, which can
      accommodate the establishment of a permissive immunogenic microenvironment to
      counteract tumor-induced immunosuppression, and cancer vaccines consisting of
      whole tumor lysates and nanogel-based adjuvants, which can generate tumor antigen
      specific T cell responses. The local peritumoral implantation of the synthetic
      immune niche (termed immuneCare-DISC, iCD) as a postsurgical treatment in an
      advanced-stage primary 4T1 breast tumor model generates systemic antitumor
      immunity and prevents tumor recurrence at the surgical site as well as the
      migration of residual tumor cells into the lungs, resulting in 100% survival.
      These therapeutic outcomes are achieved through the inhibition of
      immunosuppressive MDSCs in tumors and spleens by releasing gemcitabine and
      recruitment/activation of dendritic cells, enhanced population of CD4+ and CD8+ T
      cells, and increased IFN-gamma production by cancer vaccines from the iCD. This
      combined spatiotemporal modulation of tumor-derived immunosuppression and vaccine
      induced immune stimulation through the iCD is expected to provide an immune niche
      for prevention of postoperative tumor recurrence and metastasis.

PMID- 29572969
TI  - The prevalence of Achilles and patellar tendon injuries in Australian football
      players beyond a time-loss definition.
AB  - Little is known about the prevalence and associated of morbidity of tendon
      problems. With only severe cases of tendon problems missing games, players that
      have their training and performance impacted are not captured by traditional
      injury surveillance. The aim of this study was to report the prevalence of
      Achilles and patellar tendon problems in elite male Australian football players
      using the Oslo Sports Trauma Research Centre (OSTRC) overuse questionnaire,
      compared to a time-loss definition. Male athletes from 12 professional Australian
      football teams were invited to complete a monthly questionnaire over a 9-month
      period in the 2016 pre- and competitive season. The OSTRC overuse injury
      questionnaire was used to measure the prevalence and severity of Achilles and
      patellar tendon symptoms and was compared to traditional match-loss statistics. A
      total of 441 participants were included. Of all participants, 21.5% (95% CI: 17.9
      25.6) and 25.2% (95% CI 21.3-29.4) reported Achilles or patellar tendon problems
      during the season, respectively. Based on the traditional match-loss definition,
      a combined 4.1% of participants missed games due to either Achilles or patellar
      tendon injury. A greater average monthly prevalence was observed during the pre
      season compared to the competitive season. Achilles and patellar tendon problems
      are prevalent in elite male Australian football players. These injuries are not
      adequately captured using a traditional match-loss definition. Prevention of
      these injuries may be best targeted during the off- and pre-season due to higher
      prevalence of symptoms during the pre-season compared to during the competitive
      season.

PMID- 29572970
TI  - A Universal Strategy for Intimately Coupled Carbon Nanosheets/MoM Nanocrystals (M
      = P, S, C, and O) Hierarchical Hollow Nanospheres for Hydrogen Evolution
      Catalysis and Sodium-Ion Storage.
AB  - Intimately coupled carbon/transition-metal-based hierarchical nanostructures are
      one of most interesting electrode materials for boosting energy conversion and
      storage applications owing to the strong synergistic effect between the two
      components and appealing structural stability. Herein, a universal method is
      reported for making hierarchical hollow carbon nanospheres (HCSs) with intimately
      coupled ultrathin carbon nanosheets and Mo-based nanocrystals. The in situ and
      confined reaction of the synthetic strategy can not only allow the aggregation of
      the nanocrystals to be impeded, but also endows extremely intimate coupled
      interaction between the conductive carbon nanosheets and the nanocrystals MoM (M
      = P, S, C and O). As a proof of concept, the as-prepared MoP/C HCSs exhibit
      extraordinary hydrogen evolution reaction electrocatalytic activity with small
      overpotential and robust durability in both acidic and alkaline solutions. In
      addition, the unique sheet-on-sheet MoS2 /C HCSs as an anode demonstrate high
      capacity, great rate capabilities, and long-term cycles for sodium-ion batteries
      (SIBs). The capacity can be maintained at 410 mA h g-1 even after 1000 cycles
      even at a high current density of 4 A g-1 , one of the best reported values for
      MoS2 -based electrode materials for SIBs. The present work highlights the
      importance of designing and fabricating functional strongly coupled hybrid
      materials for enhancing energy conversion and storage applications.

PMID- 29572971
TI  - Droplet Microarrays: From Surface Patterning to High-Throughput Applications.
AB  - High-throughput screening of live cells and chemical reactions in isolated
      droplets is an important and growing method in areas ranging from studies of gene
      functions and the search for new drug candidates, to performing combinatorial
      chemical reactions. Compared with microfluidics and well plates, the facile
      fabrication, high density, and open structure endow droplet microarrays on planar
      surfaces with great potential in the development of next-generation miniaturized
      platforms for high-throughput applications. Surfaces with special wettability
      have served as substrates to generate and/or address droplets microarrays. Here,
      the formation of droplet microarrays with designed geometry on chemically
      prepatterned surfaces is briefly described and some of the newer and emerging
      applications of these microarrays that are currently being explored are
      highlighted. Next, some of the available technologies used to add (bio-)chemical
      libraries to each droplet in parallel are introduced. Current challenges and
      future prospects that would benefit from using such droplet microarrays are also
      discussed.

PMID- 29572972
TI  - Contact-Engineered Electrical Properties of MoS2 Field-Effect Transistors via
      Selectively Deposited Thiol-Molecules.
AB  - Although 2D molybdenum disulfide (MoS2 ) has gained much attention due to its
      unique electrical and optical properties, the limited electrical contact to 2D
      semiconductors still impedes the realization of high-performance 2D MoS2 -based
      devices. In this regard, many studies have been conducted to improve the carrier
      injection properties by inserting functional paths, such as graphene or hexagonal
      boron nitride, between the electrodes and 2D semiconductors. The reported
      strategies, however, require relatively time-consuming and low-yield transfer
      processes on sub-micrometer MoS2 flakes. Here, a simple contact-engineering
      method is suggested, introducing chemically adsorbed thiol-molecules as thin
      tunneling barriers between the metal electrodes and MoS2 channels. The
      selectively deposited thiol-molecules via the vapor-deposition process provide
      additional tunneling paths at the contact regions, improving the carrier
      injection properties with lower activation energies in MoS2 field-effect
      transistors. Additionally, by inserting thiol-molecules at the only one contact
      region, asymmetric carrier-injection is feasible depending on the temperature and
      gate bias.

PMID- 29572973
TI  - Textile Display for Electronic and Brain-Interfaced Communications.
AB  - Textile displays are poised to revolutionize current electronic devices, and
      reshape the future of electronics and related fields such as biomedicine and soft
      robotics. However, they remain unavailable due to the difficulty of directly
      constructing electroluminescent devices onto the textile-like substrate to really
      display desired programmable patterns. Here, a novel textile display is developed
      from continuous electroluminescent fibers made by a one-step extrusion process.
      The resulting displaying textile is flexible, stretchable, three-dimensionally
      twistable, conformable to arbitrarily curved skins, and breathable, and can
      dynamically display a series of desired patterns, making it useful for
      bioinspired electronics, soft robotics, and electroluminescent skins, among other
      applications. It is demonstrated that these displaying textiles can also
      communicate with a computer and mouse brain for smart display and camouflage
      applications. This work may open up a new direction for the integration of
      wearable electroluminescent devices with the human body, providing new and
      promising communication platforms.

PMID- 29572974
TI  - Impact of remnant vital tissue after locoregional treatment and liver transplant
      in hepatocellular cancer patients, a multicentre cohort study.
AB  - The role of pathological findings after locoregional treatments as predictors of
      hepatocellular cancer recurrence after liver transplantation has been poorly
      addressed. The aim of the study was to identify the role of remnant vital tissue
      (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two
      hundred and seventy-six patients firstly undergoing locoregional treatment and
      then transplanted between January 2010 and December 2015 in four European
      Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were
      enrolled in the study to investigate the role of pathological response at upfront
      locoregional treatment. At multivariable Cox regression analysis, RVT >=2 cm was
      a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001).
      Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients
      presenting a RVT >=2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan
      Criteria-IN patients were analysed, similar results were reported, with 5-year
      disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a
      RVT >=2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant
      of tumour recurrence after liver transplantation performed for hepatocellular
      cancer. Its discriminative power looks to be evident also in a Milan-IN setting,
      suggesting to more liberally use locoregional treatments also in these patients.

PMID- 29572975
TI  - Effects of oxidative stress induced by high dosage of dietary iron ingested on
      intestinal damage and caecal microbiota in Chinese Yellow broilers.
AB  - The objective of this trial was to test the effects of oxidative stress induced
      by a high dosage of dietary iron on intestinal lesion and the microbiological
      compositions in caecum in Chinese Yellow broilers. A total of 450 1-day-old male
      chicks were randomly allotted into three groups. Supplemental iron (0, 700 and
      1,400 mg/kg) was added to the basal diet resulting in three treatments containing
      245, 908 and 1,651 mg/kg Fe (measured value) in diet respectively. Each treatment
      consisted of six replicate pens with 25 birds per pen. Jejunal enterocyte
      ultrastructure was observed by transmission electron microscopy. The results
      showed that a high dosage of dietary iron induced oxidative stress in broilers.
      Dilated endoplasmic reticulum (ER), autophagosome formation of jejunal
      enterocytes and decreased villi were caused by this oxidative stress. Compared to
      the control, concentration of the malondialdehyde (MDA) in jejunal mucosa in the
      908 and 1,651 mg/kg Fe groups increased by 180% (p < .01) and 155% respectively
      (p < .01); activity of copper-zinc superoxide dismutase (Cu/ZnSOD) increased in
      jejunum (p < .01); and the concentration of plasma reduced glutathione (GSH)
      decreased by 34.9% (p < .01) in birds fed 1,651 mg/kg Fe. Gene expression of
      nuclear factor, erythroid-derived 2-like 2 (Nrf2) and zonula occludens-1 (ZO-1),
      in the higher dietary Fe groups was enhanced (p < .05). Species of microbial
      flora in caecum increased caused by oxidative stress. The PCR-DGGE (denaturing
      gradient gel electrophoresis) dendrograms revealed different microbiota (65%
      similarity coefficient) between the control and iron-supplemented groups (p <
      .05). These data suggest high dosage of iron supplement in feed diet can induce
      oxidative stress in Chinese Yellow broilers, and composition of microbiota in the
      caecum changed. It implied there should be no addition of excess iron when
      formulating diets in Chinese Yellow broilers.

PMID- 29572977
TI  - The value of grading dysplasia in appendiceal mucinous neoplasm in the absence of
      pseudomyxoma peritonei.

PMID- 29572976
TI  - The effect of Nordic hamstring exercise training volume on biceps femoris long
      head architectural adaptation.
AB  - The aim of this study was to determine the time course of architectural
      adaptations in the biceps femoris long head (BFLH ) following high or low volume
      eccentric training. Twenty recreationally active males completed a two week
      standardized period of eccentric Nordic hamstring exercise (NHE) training,
      followed by four weeks of high (n = 10) or low volume (n = 10) training.
      Eccentric strength was assessed pre- and post intervention and following
      detraining. Architecture was assessed weekly during training and after two and
      four weeks of detraining. After six weeks of training, BFLH fascicles increased
      significantly in the high (23% +/- 7%, P < .001, d = 2.87) and low volume (24% +/
      4%, P < .001, d = 3.46) groups, but reversed following two weeks of detraining
      (high volume: -17% +/- 5%, P < .001, d = -2.04; low volume: -15% +/- 3%, P <
      .001, d = -2.56) after completing the intervention. Both groups increased
      eccentric strength after six weeks of training (high volume: 28% +/- 20%, P =
      .009, d = 1.55; low volume: 34% +/- 14%, P < .001, d = 2.09) and saw no change in
      strength following a four week period of detraining (high volume: -7% +/- 7%, P =
      .97, d = -0.31; low volume: -2% +/- 5%, P = .99, d = -0.20). Both low and high
      volume NHE training stimulate increases in BFLH fascicle length and eccentric
      knee flexor strength. Architectural adaptations reverted to baseline levels
      within two weeks after ceasing training, but eccentric strength was maintained
      for at least four weeks. These observations provide novel insight into the
      effects of training volume and detraining on BFLH architecture and may provide
      guidance for the implementation of NHE programs.

PMID- 29572978
TI  - Ectopic epithelial cell clusters in salmonid intestine are associated with
      inflammation.
AB  - An epizootic incidence of intestinal adenocarcinomas was reported in brood fish
      of Atlantic salmon (Salmo salar L.) in 2009. The condition was associated with a
      specific diet inducing enteritis and morphological changes. Here, two field
      trials of fish up to slaughter size were initiated. In Trial 1, two different
      feed recipes were used. Feed I was predominantly based on marine ingredients,
      whereas plant ingredients were limited to soy protein concentrate and wheat. Feed
      II was lower in fishmeal and without soya protein, which was substituted with
      plant proteins from other sources. In Trial 2, a commercial feed (Feed III) was
      included. No macroscopic tumours were observed in 300 fish (Trial 1). At the end
      of both trials, samples from five different segments of the gastrointestinal
      tract of a total of 39 fish were investigated with morphological methods. Here,
      we show the presence of ectopic proliferating epithelial cells only occurring in
      inflamed intestine and predominantly in the second segment of the mid-intestine.
      Presence of ectopic epithelial cells in submucosal inflammatory foci may indicate
      early stages in tumorigenesis, but other possibilities such as proliferative
      enteric disorders cannot be excluded. Together with inflammation, carcinogenesis
      should be a focus of investigation in future feed trials.

PMID- 29572979
TI  - Functional, RF-Trilayer Sensors for Tooth-Mounted, Wireless Monitoring of the
      Oral Cavity and Food Consumption.
AB  - Wearable devices have emerged as powerful tools for personalized healthcare in
      spite of some challenges that limit their widespread applicability as continuous
      monitors of physiological information. Here, a materials-based strategy to add
      utility to traditional dielectric sensors by developing a conformal
      radiofrequency (RF) construct composed of an active layer encapsulated between
      two reverse-facing split ring resonators is applied. These small (down to 2 mm *
      2 mm) passive dielectric sensors possess enhanced sensitivity and can be further
      augmented by functionalization of this interlayer material. Demonstrator devices
      are shown where the interlayer is: (i) a porous silk film, and (ii) a modified
      PNIPAM hydrogel that swells with pH or temperature. In vivo use is demonstrated
      by adhesion of the device on tooth enamel to detect foods during human ingestion.
      Such sensors can be easily multiplexed and yield data-rich temporal information
      during the diffusion of analytes within the trilayer structure. This format could
      be extended to a suite of interlayer materials for sensing devices of added use
      and specificity.

PMID- 29572980
TI  - Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living
      Systems.
AB  - This concept article focuses on the rapid growth of intracellular chemistry
      dedicated to the integration of small-molecule metal catalysts with living cells
      and organisms. Although biological systems contain a plethora of biomolecules
      that can deactivate inorganic species, researchers have shown that small-molecule
      metal catalysts could be engineered to operate in heterogeneous aqueous
      environments. Synthetic intracellular reactions have recently been reported for
      olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition,
      allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation.
      Other promising targets for new biocompatible reaction discovery will also be
      discussed, with a special emphasis on how such innovations could lead to the
      development of novel technologies and chemical tools.

PMID- 29572981
TI  - Survival and mortality of adult-onset myasthenia gravis in the population of
      Belgrade, Serbia.
AB  - INTRODUCTION: The objective of this study was to estimate mortality and survival
      in a large cohort of myasthenia gravis (MG) patients from Belgrade, Serbia,
      during the period 1979-2008. METHODS: Data for all patients with MG were
      collected from hospital records and the Belgrade MG Registry. RESULTS: Within the
      30-year study period, death occurred in 107 (20%) of 562 patients with MG, with
      MG-related fatality below 2%. The average MG mortality rate was 1.76 per
      1,000,000 population (1.26/1,000,000 women, 2.45/1,000,000 men). A statistically
      significant increase was recorded for the average standardized mortality rate for
      all patients (P < 0.01). The mean survival from disease onset was 34.3 +/- 2.0
      years. Significantly shorter survival was observed in men compared with women and
      in patients older than 50 years compared with younger ones (P < 0.01).
      DISCUSSION: We observed long survival and low frequency of MG-related fatalities
      but increasing average standardized mortality rate, most notably in older men
      with MG. Muscle Nerve 58: 708-712, 2018.

PMID- 29572982
TI  - An update on the biophysical character of the human eukaryotic elongation factor
      1 beta: Perspectives from interaction with elongation factor 1 gamma.
AB  - The beta-subunit of the human eukaryotic elongation factor 1 complex (heEF1beta)
      plays a central role in the elongation step in eukaryotic protein biosynthesis,
      which essentially involves interaction with the alpha- and gamma-subunits
      (eEF1gamma). To biophysically characterize heEF1beta, we constructed 3
      Escherichia coli expression vector systems for recombinant expression of the full
      length (FL-heEF1beta), N-terminus (NT-heEF1beta), and the C-terminus (CT
      heEF1beta) regions of the protein. Our results suggest that heEF1beta is
      predominantly alpha-helical and possesses an accessible hydrophobic cavity in the
      CT-heEF1beta. Both FL-heEF1beta and NT-heEF1beta form dimers of size 62 and 30
      kDa, respectively, but the CT-heEF1beta is monomeric. FL-heEF1beta interacts with
      the N-terminus glutathione transferase-like domain of heEF1gamma (NT-heEF1gamma)
      to form a 195-kDa complex or a 230-kDa complex in the presence of oxidized
      glutathione. On the other hand, NT-heEF1beta forms a 170-kDa complex with NT
      heEF1gamma and a high molecular weight aggregate of size greater than 670 kDa.
      Surface plasmon resonance analysis confirmed that (by fitting the Langmuir 1:1
      model) FL-heEF1beta associated with monomeric or dimeric NT-heEF1gamma at a rapid
      rate and slowly dissociated, suggesting strong functional affinity (KD  = 9.6 nM
      for monomeric or 11.3 nM for dimeric NT-heEF1gamma). We postulate that the N
      terminus region of heEF1beta may be responsible for its dimerization and the C
      terminus region of heEF1beta modulates the formation of an ordered heEF1beta
      gamma oligomer, a structure that may be essential in the elongation step of
      eukaryotic protein biosynthesis.

PMID- 29572983
TI  - Halogen, Chalcogen, and Pnicogen Bonding Involving Hypervalent Atoms.
AB  - The additional substituents arising from hypervalency present a number of
      complicating issues for the formation of noncovalent bonds. The XF5 molecule
      (X=Cl, Br, I) was allowed to form a halogen bond with NH3 as the base.
      Hypervalent chalcogen bonding is examined by way of YF4 and YF6 (Y=S, Se, Te),
      and ZF5 (Z=P, As, Sb) is used to model pnicogen bonding. Pnicogen bonds are
      particularly strong, with interaction energies approaching 50 kcal mol-1 , and
      also involve wholesale rearrangement from trigonal bipyramidal in the monomer to
      square pyramidal in the complex, subject to a large deformation energy. YF4
      chalcogen bonding is also strong, and like pnicogen bonding, is enhanced by a
      heavier central atom. XF5 halogen bond energies are roughly 9 kcal mol-1 , and
      display a unique sensitivity to the identity of the X atom. The crowded
      octahedral structure of YF6 permits only very weak interactions. As the F atoms
      of SeF6 are replaced progressively by H, a chalcogen bond appears in combination
      with SeH???N and NH???F H-bonds. The strongest such chalcogen bond appears in
      SeF3 H3 ???NH3 , with a binding energy of 7 kcal mol-1 , wherein the base is
      located in the H3 face of the Lewis acid. Results are discussed in the context of
      the way in which the positions and intensities of sigma-holes are influenced by
      the locations of substituents and lone electron pairs.

PMID- 29572984
TI  - Total Synthesis of Lapidilectine B Enabled by Manganese(III)-Mediated Oxidative
      Cyclization of Indoles.
AB  - A novel manganese(III)-mediated oxidative cyclization of readily accessible 1,2,3
      trisubstituted indoles is described. This unprecedented method enabled the
      efficient construction of a complex polycyclic scaffold bearing a spiro-indoline
      motif and a lactone moiety in one step. Its synthetic utility was demonstrated in
      the total synthesis of lapidilectine B (in 18 steps) by employing a strategic
      regioselective ring-expansion and a silver-promoted allenic amine cyclization as
      the additional key elements.

PMID- 29572985
TI  - Structure of Ancient Glass by 29 Si Magic Angle Spinning NMR Spectroscopy.
AB  - 29 Si magic angle spinning (MAS) NMR spectroscopy has been applied for the first
      time to the structural analysis of ancient glass samples obtained from
      archaeological excavations. The results show that it is possible to establish the
      distribution of Si environments in ancient glass by 29 Si MAS NMR, so long as the
      concentrations of magnetic impurities, such as Mn and Fe oxides, are low. In
      general, good agreement has been obtained with compositions determined by means
      of electron probe microanalysis. In addition, the 29 Si MAS NMR data reveal
      structural differences between glasses manufactured at separate ancient sites.

PMID- 29572986
TI  - Dynamics of formation and morphological features of neutrophil extracellular
      traps formed under the influence of opsonized Staphylococcus aureus.
AB  - In the process of performing their protective functions, neutrophils can form
      neutrophil extracellular traps (NETs), consisting of DNA in combination with
      enzymes and histones. The aim of the study was to determine the dynamics of the
      formation of NETs under the influence of opsonized Staphylococcus aureus and to
      determine the morphological features of their development in real time by atomic
      force microscopy. It was found that the maximum formation of NETs was observed
      after 3 hours of co-incubation of neutrophils and opsonized S. aureus. For the
      first time, the atomic force microscopy method revealed that, at first, large
      blocks of parallel DNA helices are formed, which then spread in waves, and only
      then their bifurcation and separation can be observed. Some of the strands formed
      are covered by a shell, which subsequently completely disappears. Enzymes and
      histones become clearly visible only after 140 to 150 minutes of observation. The
      DNA helixes move toward the opsonized S. aureus. After NET formation, the cell
      remains on the substrate only in the form of traces of focal adhesion. This, and
      the fact that the maximum amount of NETs is formed after 3 hours of co-incubation
      with opsonized S. aureus, suggests that the formation of NETs follows the
      classical mechanism. The study of the dynamics of formation and the
      microstructure of NETs makes it possible to estimate the time frame for the
      implementation of this protective mechanism of the human body when performing the
      compensatory inflammatory reaction.

PMID- 29572987
TI  - Chemical and Absorption Signatures of Xiao Chai Hu Tang.
AB  - RATIONALE: Xiao Chai Hu Tang (XCHT, Sho-saiko-to in Japanese) is a well-known
      medicine formula used in Asia for centuries. However, the quality control and the
      absorption of XCHT components are the major remaining concerns.. The study was to
      develop a sensitive and robust method to characterize the chemical components in
      XCHT and evaluate their absorptions. METHODS: An ultra-high pressure liquid
      chromatography coupled with electrospray ionization quadrupole time-of-flight
      mass spectrometry (UHPLC-ESI-QTOF MS/MS) was used to identify the compounds in
      XCHT. The Caco-2 cell culture model was employed to determine the absorption of
      the identified components. RESULTS: The results showed that 109 compounds were
      identified including organic acids, flavonoids, saikosaponins, ginsenosides,
      licoricesaponins and gingerols. The absorption study showed that among those
      identified, 33 compounds have decent absorption permerbilities ranging from 1.46
      +/- 0.24*10-7 to 3.10+/-0.61*10-5 cm/sec. These compounds were classified as
      classes II and IV in the biopharmaceutical classification system (BCS).
      CONCLUSIONS: These identified compounds could be used to characterize quality of
      XCHT and those absorbed compounds with decent permreabiliteis are the potential
      active components in XCHT. Future pharmacodynamics studies should focus on these
      absorbed compounds.

PMID- 29572988
TI  - Nonvolatile Tri-State Resistive Memory Behavior of a Stable Pyrene-Fused N
      Heteroacene with Ten Linearly-Annulated Rings.
AB  - The diverse functionalities of large N-heteroacenes continue to be developed in
      terms of their strategic synthesis and application in the organic electronic
      field. Here, we report a novel large stable pyrene-containing N-heteroacene with
      ten linearly-annulated rings in one row. Remarkably, it exhibited excellent tri
      state resistive memory property, which held great promise to achieve ultrahigh
      density data storage. To the best of our knowledge, it is the first demonstration
      of organic multistate memory device based on large N-heteroacene (n>=10), which
      provides guidelines for designing more proof-of-concept larger N-heteroacene
      based memory electronics.

PMID- 29572989
TI  - Development of a multi-functional concurrent assay using weak cation-exchange
      solid-phase extraction (WCX-SPE) and reconstitution with a diluted sample aliquot
      for anti-doping analysis.
AB  - RATIONALE: In addition to the development of adequate screening methods for
      multiple compounds, the World Anti-Doping Agency (WADA) requires anti-doping
      laboratories to analyze prohibited substances and their metabolites from various
      classes. This task presents a difficult challenge for all agencies and interests
      involved in the field of doping control. METHODS: A screening method is reported
      in which hybrid sample preparation was performed using a combination of weak
      cation-exchange solid-phase extraction (WCX-SPE) and the 'Dilute and Shoot'
      strategy in order to take advantage of both the methodologies. Target substances
      were extracted using a WCX cartridge and reconstituted with a diluted sample
      aliquot that included 20% of an untreated urine sample. The target substances
      were further analyzed by high-performance liquid chromatography/triple quadrupole
      mass spectrometry (LC/MS). RESULTS: The SPE procedure was optimized using a
      cartridge-washing step, elution conditions, and elution volume. The cartridge
      washing step, which was performed using 10% methanol, improved the overall
      recovery of target substances. Since the recovery was observed to vary according
      to the pH of the eluting solution, we applied an elution step using both an acid
      and a basic organic solvent to achieve complementary recovery. Reconstitution of
      the diluted aliquot sample was performed to recover the polar substances.
      CONCLUSIONS: The method was validated and applied to real samples in accordance
      with the external quality assessment scheme of WADA and to the previously
      reported samples that had provided positive test results. This novel method using
      hybrid sample preparation and LC/MS could be useful to screen multiple classes of
      the 264 targeted substances in anti-doping analysis.

PMID- 29572990
TI  - Machine learning RF shimming: Prediction by iteratively projected ridge
      regression.
AB  - PURPOSE: To obviate online slice-by-slice RF shim optimization and reduce B1+
      mapping requirements for patient-specific RF shimming in high-field magnetic
      resonance imaging. THEORY AND METHODS: RF Shim Prediction by Iteratively
      Projected Ridge Regression (PIPRR) predicts patient-specific, SAR-efficient RF
      shims with a machine learning approach that merges learning with training shim
      design. To evaluate it, a set of B1+ maps was simulated for 100 human heads for a
      24-element coil at 7T. Features were derived from tissue masks and the DC Fourier
      coefficients of the coils' B1+ maps in each slice, which were used for kernelized
      ridge regression prediction of SAR-efficient RF shim weights. Predicted shims
      were compared to directly designed shims, circularly polarized mode, and nearest
      neighbor shims predicted using the same features. RESULTS: PIPRR predictions had
      87% and 13% lower B1+ coefficients of variation compared to circularly polarized
      mode and nearest-neighbor shims, respectively, and achieved homogeneity and SAR
      similar to that of directly designed shims. Predictions were calculated in 4.92
      ms on average. CONCLUSION: PIPRR predicted uniform, SAR-efficient RF shims, and
      could save a large amount of B1+ mapping and computation time in RF-shimmed ultra
      high field magnetic resonance imaging.

PMID- 29572991
TI  - Self-Assembled Bright Luminescent Lanthanide-Organic Polyhedra for Ratiometric
      Temperature Sensing.
AB  - Luminescent lanthanide-containing compounds have a lot of stimulating
      applications. However, the fine-tuning of the optical properties of multi-nuclear
      lanthanide edifices is still a big challenge. We report here the coordination
      self-assembly of a group of bright luminescent lanthanide organic polyhedra
      (LOPs) with record high emission quantum yields, by using two fully-conjugated
      ligands featuring the triazole-pyridine-amido (tpa) chelating moiety, easily
      accessible from the "Click" reaction. The self-assembled LOPs are characterized
      by NMR spectroscopy, high-resolution ESI-TOF-MS, and X-ray crystallography.
      Interestingly, inter-metal energy transfer (ET) is confirmed on the mixed
      lanthanide polyhedral molecules, though the metal centers are separated nearly 2
      nm apart. A feasible ratiometric luminescent thermometer, with work range from
      cryogenic to physiological temperatures, has been demonstrated with the mixed
      Eu/Tb LOPs. We envisage these molecular-level bright luminescent LOPs have great
      application potential in displaying, labelling/imaging, up-conversion materials
      etc.

PMID- 29572992
TI  - Therapeutic Nanoreactors as In Vivo Nanoplatforms for Cancer Therapy.
AB  - Therapeutic nanoreactors have been proposed as nanoplatforms to treat diseases
      through in situ production of therapeutic agents. When this treatment strategy is
      applied in cancer therapy, it can efficiently produce highly toxic anticancer
      drugs in situ from low-toxic prodrugs or some biomolecules in tumor tissues,
      which can maximize the therapeutic efficacy with a significantly low systemic
      toxicity. An ideal therapeutic nanoreactor can provide the reaction space,
      protect the loaded fragile catalysts, target the desired pathological site, and
      be selectively activated. In this minireview, we highlight the recent advances
      concerning the applications of therapeutic nanoreactors as in vivo nanoplatforms
      particularly in cancer therapy. Herein, the therapeutic nanoreactors are
      discussed on the basis of treatment strategies and various nanoparticles.
      Specifically, the treatment strategies of nanoreactors including single enzyme,
      single enzyme with chemodrugs, and multienzymes, as well as varying types of
      engineered nanoparticle-loaded active catalysts, primarily including liposomes,
      polymersomes, polymeric micelles, inorganic nanoparticles, and metal-organic
      framework (MOF) architectures, are documented and briefly discussed. Finally, we
      elucidate the current challenges to be addressed toward further development and
      translation into clinical applications of these therapeutic nanoreactors in
      cancer therapy.

PMID- 29572993
TI  - Hierarchical Mesoporous Organosilica-Silica Core-Shell Nanoparticles Capable of
      Controlled Fungicide Release.
AB  - A new class of hierarchically structured mesoporous silica core-shell
      nanoparticles (HSMSCSNs) with a periodic mesoporous organosilica (PMO) core and a
      mesoporous silica (MS) shell is reported. The applied one-pot, two-step strategy
      allows rational control over the core/shell chemical composition, topology, and
      pore/particle size, simply by adjusting the reaction conditions in the presence
      of cetyltrimethylammonium bromide (CTAB) as structure-directing agent under basic
      conditions. The spherical, ethylene- or methylene-bridged PMO cores feature
      hexagonal (p6mm) or cage-like cubic symmetry (Pm3? n) depending on the
      organosilica precursor. The hexagonal MS shell was obtained by n-hexane-induced
      controlled hydrolysis of TEOS followed by directional co-assembly/condensation of
      silicate/CTAB composites at the PMO cores. The HSMSCSNs feature a hierarchical
      pore structure with pore diameters of about 2.7 and 5.6 nm in the core and shell
      domains, respectively. The core sizes and shell thicknesses are adjustable in the
      ranges of 90-275 and 15-50 nm, respectively, and the surface areas (max. 1300 m2 
      g-1 ) and pore volumes (max. 1.83 cm3  g-1 ) are among the highest reported for
      core-shell nanoparticles. The adsorption and controlled release of the fungicide
      propiconazole by the HSMSCSNs showed a three-stage release profile.

PMID- 29572994
TI  - Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's
      Disease.
AB  - BACKGROUND: Gastrointestinal symptoms are common in Parkinson's disease and
      frequently precede the development of motor impairments. Intestinal inflammation
      has been proposed as a driver of disease pathology, and evaluation of
      inflammatory mediators in stool could possibly identify valuable early-stage
      biomarkers. We measured immune- and angiogenesis-related proteins in human stool
      to examine inflammatory profiles associated with Parkinson's disease. METHODS:
      Stool samples and subjects' self-reported metadata were obtained from 156
      individuals with Parkinson's disease and 110 without, including spouse and
      nonhousehold controls. Metadata were probed for disease-associated differences,
      and levels of 37 immune and angiogenesis factors in stool homogenates were
      measured by multiplexed immunoassay and compared across experimental groups.
      RESULTS: Parkinson's disease patients reported greater incidence of intestinal
      disease and digestive problems than controls. Direct comparison of levels of
      stool analytes in patients and controls revealed elevated vascular endothelial
      growth factor receptor 1, interleukin-1alpha, and CXCL8 in patients' stool.
      Paired comparison of patients and spouses suggested higher levels of multiple
      factors in patients, but this was complicated by sex differences. Sex, body mass
      index, a history of smoking, and use of probiotics were found to strongly
      influence levels of stool analytes. Multivariate analysis accounting for these
      and other potential confounders confirmed elevated levels of interleukin-1alpha
      and CXCL8 and also revealed increased interleukin-1beta and C-reactive protein in
      stool in Parkinson's disease. These differences were not dependent on subject age
      or disease duration. CONCLUSIONS: Levels of stool immune factors indicate that
      intestinal inflammation is present in patients with Parkinson's disease. (c) 2018
      International Parkinson and Movement Disorder Society.

PMID- 29572995
TI  - An Improved Approach to the Direct Construction of 2-Deoxy-beta-Linked Sugars:
      Applications to Oligosaccharide Synthesis.
AB  - A next-generation reagent-controlled approach for the synthesis of 2,6-dideoxy
      and 2,3,6-trideoxy sugar donors in good yield and high beta-selectivity is
      reported. The use of p-toluenesulfonyl chloride and potassium
      hexamethyldisilazide (KHMDS) greatly simplifies deoxy-sugar glycoside
      construction, and can be used for gram-scale glycosylation reactions. The
      development of this approach and its application to the construction of beta
      linked deoxy-sugar oligosaccharides are described.

PMID- 29572996
TI  - Synthesis and Characterization of Photothermal Osmium Carbolong Complexes.
AB  - Metallacycles with chelating polydentate conjugated-carbon chain ligands are
      called carbolong complexes, which are expected to have interesting properties. In
      this work, the preparation of 12-carbon carbolong complexes in which all of the
      coordinated atoms in the equatorial plane are carbon atoms was studied. With the
      help of the well-established mechanism, a new approach to prepare coplanar
      carbolong complexes bearing different organic functional groups was developed by
      adding different terminal alkynes in sequence. In the presence of HBF4 , these
      coplanar carbolong complexes were converted to eta3 -allyl osmapentalene
      derivatives, which can be produced directly from the reaction of
      cyclopropaosmapentalene 1 with terminal alkynes in the presence of AgBF4 under
      anhydrous conditions. This study offers a new route for the preparation of
      functional osmium carbolong complexes with excellent photothermal properties,
      which can be used to prepare photothermal materials.

PMID- 29572997
TI  - Microbial communities inhabiting the fairy ring of Floccularia luteovirens and
      isolation of potential mycorrhiza helper bacteria.
AB  - Floccularia luteovirens, an important edible mushroom widely distributed in the
      Qinghai-Tibet plateau, is ecologically important as an ectomycorrhizal fungus and
      can form the fairy ring. To explore the influence of F. luteovirens fairy ring on
      soil microbial communities, we compared the soil microbial communities in three
      different fairy ring zones (inside the fairy ring (IN); beneath the fairy ring
      (ON); and outside the fairy ring (OUT)). A total of 1.77 million bacterial reads
      and 1.59 million fungal reads were obtained. Moreover, sequence clustering
      yielded 519,613 (57,735 per sample) bacterial OTUs, and 513,204 (57,023 per
      sample) fungal OTUs representing. Microbial diversity was lower in samples from
      the ON zone compared with the other two zones. Mycorrhiza helper bacteria (MHB)
      such as Bradyrhizobium and Paenibacillus were more common in the ON zone, and we
      isolated four potential MHB from rhizosphere soil. Canonical correspondence
      analysis showed that the soil nutritional condition and physical changes caused
      by F. luteovirens shaped the microbial communities in the ON zone. This is the
      first report on the study of soil microbial diversity influenced by fairy ring F.
      luteovirens, and further studies need to be conducted to study the ecological
      function influenced by this species.

PMID- 29572998
TI  - Ligand-Based Storage of Protons and Electrons in Dihydrazonopyrrole Complexes of
      Nickel.
AB  - A newly developed dihydrazonopyrrole ligand and corresponding Ni complexes have
      been synthesized and thoroughly characterized. Electrochemical studies and
      chemical reactivity tests show that these complexes can reversibly store both
      electrons and protons, or equivalently H-atoms, via ligand-based events. The
      stored H-atom equivalent can be transferred to small molecules such as
      acetonitrile or oxygen. Furthermore, this series of complexes can adopt a variety
      of different coordination modes. In addition to one e- reactivity, the two e-
      electrophilic oxidation of phosphines is also demonstrated. Taken together, these
      results show that dihydrazonopyrrole complexes represent a geometrically and
      electronically flexible scaffold for controlling the flow of both electrons and
      protons.

PMID- 29572999
TI  - A Facile Synthesis of Blue Luminescent [7]Helicenocarbazoles Based on Gold
      Catalyzed Rearrangement-Iodonium Migration and Suzuki-Miyaura Benzannulation
      Reactions.
AB  - New azahelicenes having interesting photophysical properties have been prepared
      in a four-step sequence. These [7]helicenocarbazoles are efficient blue
      luminophores, demonstrating the utility of gold catalysis in the preparation of
      advanced materials.

PMID- 29573000
TI  - What is going on in underage drinking? Reflections on Finnish European school
      survey project on alcohol and other drugs data 1999-2015.
AB  - INTRODUCTION AND AIMS: As alcohol use has decreased among Finnish adolescents, we
      aim to assess: (i) time trends in alcohol use, heavy episodic drinking (HED) and
      potential explanatory variables among adolescents; (ii) the relationship between
      trends of explanatory variables and trends in alcohol use and HED; and (iii)
      which of the explanatory variables can account for the temporal change in alcohol
      use and HED. DESIGN AND METHODS: The analyses are based on European School Survey
      Project on Alcohol and Other Drugs data collected from 15- to 16-year-old Finnish
      adolescents in 1999, 2003, 2007, 2011 and 2015. RESULTS: The decline in alcohol
      use and HED among underage youth in Finland is associated with at least three
      factors: (i) obtaining alcohol has become more difficult; (ii) parents know
      better than before where their children spend their Friday nights; and (iii) the
      risk attached to going out with friends on drinking has decreased. DISCUSSION AND
      CONCLUSIONS: Formal policy measures and adults' attitudes have probably affected
      the availability of alcohol for adolescents, and thus they partly explain the
      decline in youth drinking. This decline coincides with the introduction of new
      digital technologies, new forms of interaction within families and peer groups,
      and more conscientious teenagers. All these changes are not necessarily causes of
      the decline but are part of a similar broader change in adolescents' lives.

PMID- 29573001
TI  - Cadaveric study validating in vitro monitoring techniques to measure the failure
      mechanism of glenoid implants against clinical CT.
AB  - Definite glenoid implant loosening is identifiable on radiographs, however,
      identifying early loosening still eludes clinicians. Methods to monitor glenoid
      loosening in vitro have not been validated to clinical imaging. This study
      investigates the correlation between in vitro measures and CT images. Ten
      cadaveric scapulae were implanted with a pegged glenoid implant and fatigue
      tested to failure. Each scapulae were cyclically loaded superiorly and CT scanned
      every 20,000 cycles until failure to monitor progressive radiolucent lines.
      Superior and inferior rim displacements were also measured. A finite element (FE)
      model of one scapula was used to analyze the interfacial stresses at the
      implant/cement and cement/bone interfaces. All ten implants failed inferiorly at
      the implant-cement interface, two also failed at the cement-bone interface
      inferiorly, and three showed superior failure. Failure occurred at of 80,966 +/-
      53,729 (mean +/- SD) cycles. CT scans confirmed failure of the fixation, and in
      most cases, was observed either before or with visual failure. Significant
      correlations were found between inferior rim displacement, vertical head
      displacement and failure of the glenoid implant. The FE model showed peak tensile
      stresses inferiorly and high compressive stresses superiorly, corroborating
      experimental findings. In vitro monitoring methods correlated to failure
      progression in clinical CT images possibly indicating its capacity to detect
      loosening earlier for earlier clinical intervention if needed. Its use in
      detecting failure non-destructively for implant development and testing is also
      valuable. The study highlights failure at the implant-cement interface and early
      signs of failure are identifiable in CT images. (c) 2018 The Authors. Journal of
      Orthopaedic Research(r) Published by Wiley Periodicals, Inc. on behalf of the
      Orthopaedic Research Society. J Orthop Res 36:2524-2532, 2018.

PMID- 29573002
TI  - Unusually Long-Wavelength Emissions of Cyclopropanes: New Insight into C-C Bond
      Homolysis.
AB  - Bond homolysis (BHo) is a fundamental concept in chemical-bonding phenomena. To
      date, research studies on the BHo concept have provided crucial information for
      understanding the nature of chemical bonding and reactions. Two potential-energy
      minima, a sigma-bonding isomer and a singlet-diradical isomer, have been known to
      exist in carbon-carbon BHo. Herein, a third isomer, that is, a puckered singlet
      diradical exhibiting unstructured long-wavelength fluorescence beyond 460 nm, was
      first observed in the excited states of 1,4-diarylbicyclo[2.1.0]pentane
      derivatives. The careful selection of appropriate substituents in the bicyclic
      structures enabled direct spectral detection. State-of-the-art ab initio quantum
      chemical calculations quantitatively reproduced the experimental observations.
      This new finding provides new insight into carbon-carbon bond-breaking and 
      forming processes.

PMID- 29573003
TI  - Phosphorescence Through Hindered Motion of Pure Organic Emitters.
AB  - This minireview deals with the phenomenon of room-temperature phosphorescence
      induced by aggregation or crystallisation. Recent achievements, as well as novel
      classes of these unique luminophores, are put in to focus. In this fashion,
      different compounds, which reveal delayed fluorescence or phosphorescence upon
      fixation in a crystal lattice or within aggregates are described. Furthermore,
      the photophysical properties, the origin of the long-lived triplet states, and
      the possible applications of these fascinating classes of molecules are also
      discussed. To conclude, a short overview about the state of art in the field of
      pure organic phosphors at room temperature is presented.

PMID- 29573004
TI  - RAD-seq linkage mapping and patterns of segregation distortion in sedges: meiosis
      as a driver of karyotypic evolution in organisms with holocentric chromosomes.
AB  - Meiotic drive, the class of meiotic mechanisms that drive unequal segregation of
      alleles among gametes, may be an important force in karyotype evolution. Its role
      in holocentric organisms, whose chromosomes lack localized centromeres, is poorly
      understood. We crossed two individuals of Carex scoparia (Cyperaceae) with
      different chromosome numbers (2n = 33II  = 66 * 2n = 32II  = 64) to obtain F1
      individuals, which we then self-pollinated to obtain second-generation (F2)
      crosses. RAD-seq was performed for 191 individuals (including the parents, five
      F1 individuals and 184 F2 individuals). Our F2 linkage map based on stringent
      editing of the RAD-seq data set yielded 32 linkage groups. In the final map, 865
      loci were located on a linkage map of 3966.99 cM (linkage groups ranged from
      24.39 to 193.31 cM in length and contained 5-51 loci each). Three linkage groups
      exhibit more loci under segregation distortion than expected by chance; within
      linkage groups, loci exhibiting segregation distortion are clustered. This
      finding implicates meiotic drive in the segregation of chromosome variants,
      suggesting that selection of chromosome variants in meiosis may contribute to the
      establishment and fixation of chromosome variants in Carex, which is renowned for
      high chromosomal and species diversity. This is an important finding as previous
      studies demonstrate that chromosome divergence may play a key role in
      differentiation and speciation in Carex.

PMID- 29573005
TI  - Bocca's hemipharyngo-total laryngectomy for hypopharyngeal carcinoma to avoid
      reconstruction with a pedicled flap.
AB  - BACKGROUND: Major pharyngeal defects after total pharyngolaryngectomy for
      hypopharyngeal squamous cell carcinoma (SCC) frequently demand reconstruction
      strategies that include myocutaneous pedicled flaps, such as the pectoralis major
      flap. METHODS: We retrospectively reviewed the clinical charts of 24 patients
      with hypopharyngeal SCC treated with Bocca's hemipharyngo-total laryngectomy
      (HPTL) at our Institution. RESULTS: Eighteen patients (80%) experienced no
      disease recurrence after primary surgery and were alive with no evidence of
      disease after a mean follow-up of 43 months. The 2-year overall survival (OS) and
      disease-specific survival (DSS) rates in our sample were 69% and 82%,
      respectively. CONCLUSION: Bocca's HPTL enables an immediate neopharyngeal
      reconstruction, and is indicated in selected patients with intermediate to
      advanced hypopharyngeal tumors.

PMID- 29573006
TI  - Ubiquitin-specific protease 4 is an endogenous negative regulator of metabolic
      dysfunctions in nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis,
      insulin resistance and inflammation, poses a high risk of cardiometabolic
      disorders. Ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme, is
      pivotally involved in regulating multiple inflammatory pathways; however, the
      role of USP4 in NAFLD is unknown. Here we report that USP4 expression was
      dramatically downregulated in the livers from NAFLD patients and different NAFLD
      mouse models induced by a high fat diet (HFD) or a genetic deficiency (ob/ob) as
      well as in palmitate-treated hepatocytes. Hepatocyte-specific USP4 depletion
      exacerbated hepatic steatosis, insulin resistance and inflammatory response in
      HFD-induced NAFLD mice. Conversely, hepatic USP4 overexpression notably
      alleviated the pathological alterations in two different NAFLD models.
      Mechanistically, hepatocyte USP4 directly bound to and deubiquitinated
      transforming growth factor-beta activated kinase 1 (TAK1), leading to a
      suppression of the activation of downstream NF-kappaB and JNK cascades, which in
      turn reversed the disruption of the IRS-AKT-GSK3beta signaling. In addition, USP4
      TAK1 interaction and subsequent TAK1 deubiquitination were required for the
      amelioration of metabolic dysfunctions. Collectively, the present study provides
      the first evidence that USP4 functions as a pivotal suppressor in NAFLD and
      related metabolic disorders. This article is protected by copyright. All rights
      reserved.

PMID- 29573007
TI  - Patients' readiness for discharge: Predictors and effects on unplanned
      readmissions, emergency department visits and death.
AB  - AIM: To determine the variables that affect patients' perceptions about their
      readiness for discharge and to elucidate the effects of these perceptions on
      patient outcomes such as unplanned readmission to the hospital, emergency
      department visits and death within 30 days after discharge. BACKGROUND: In recent
      years, it has become even more important to assess patients' readiness for
      discharge as patients tend to be discharged more quickly. METHODS: For the
      determination of patients' self-assessment, the Readiness for Hospital Discharge
      Scale/Short Form was utilized. This 1-year prospective cohort study included
      1,601 patients. Data were analysed using a chi-square test, Mann-Whitney U test,
      univariate logistic regression analysis and multiple logistic regression
      analysis. RESULTS: The results of multiple logistic regression analysis revealed
      that age, sex, marital status, educational status, presence of someone to help at
      home after discharge and length of stay were predictors of patients' readiness
      for hospital discharge. Furthermore, being unready for discharge increased the
      risk of 30 day unplanned readmission and 30 day death. CONCLUSIONS: Considering
      these predictors, patients' perceptions of readiness for discharge must be
      assessed before deciding to discharge them. IMPLICATIONS FOR NURSING MANAGEMENT:
      Nurse managers can consider the predictors of patients' readiness for discharge,
      thus the risk of unplanned readmission and death may be reduced.

PMID- 29573008
TI  - Naphtho[1,2-b:5,6-b']dithiophene-Based Conjugated Polymers for Fullerene-Free
      Inverted Polymer Solar Cells.
AB  - Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different
      aromatic rings as pi bridges and different core side substitutions are designed
      and synthesized (PzNDT-T-1,3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2
      ethylhexyl)benzo[1,2-c:4,5-c']-dithiophene-4,8-dione (BDD), PzNDT-TT-BDD, and
      PzNDTP-T-BDD, respectively). The 2D conjugation structure and molecular planarity
      of the polymers can be effectively altered through the modification of conjugated
      side chains and pi-bridges. These alterations contribute to the variation in
      energy levels, light absorption capacity, and morphology compatibility of the
      polymers. When blended with the nonfullerene acceptor (2,2'-[(4,4,9,9-tetrahexyl
      4,9-dihydro-sindaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis[methylidyne(3-oxo-1H
      indene-2,1(3H)-diylidene)]]bis-propanedinitrile) (IDIC), PzNDT-T-BDD exhibits the
      highest power conversion efficiency (PCE) of 9.72% among the three polymers. This
      result can be attributed to its superior crystallinity and more obvious face-on
      orientation in blending film. PzNDT-TT-BDD and PzNDTP-T-BDD present PCE values of
      8.20% and 4.62%, respectively. The alteration of polymer structure, particularly
      the modification of conjugated side chains and pi-bridges, is an effective
      strategy for designing NDT-based polymers with high photovoltaic performance and
      potential applications in fullerene-free solar cells.

PMID- 29573010
TI  - Do public expenditures on health and families relate to alcohol abstaining in
      adolescents? Multilevel study of adolescents in 24 countries.
AB  - INTRODUCTION AND AIMS: Several European countries have observed an increase in
      the proportion of adolescents that abstain from drinking alcohol in the last
      decade. The reasons for this trend remain underexplored. We hypothesised that
      more generous government expenditures on health services and benefits to families
      with children relate to a positive trend in abstainers. DESIGN AND METHODS: We
      used data on 15-year-olds in four successive cycles of the World Health
      Organization Health Behaviour in School-aged Children study (2002 to 2014) in 24
      North American and European countries (pooled n = 175 331). Generalised linear
      mixed-effects models were tested to analyse trends in alcohol abstinence and to
      investigate whether cross-country differences in these trends relate to public
      expenditures on health and families with children (in proportion to gross
      domestic product). RESULTS: Overall, we observed an increase in the proportion of
      abstainers from 21% in 2002 to 35% in 2014. An exception was Greece where
      abstaining had decreased from 20% to 15%. Similar results were found in boys and
      girls. The upward trend in abstinence related to larger government expenditures
      on health and families. DISCUSSIONS AND CONCLUSIONS: More generous expenditures
      on health services and family benefits relate to more adolescents abstaining from
      alcohol.

PMID- 29573009
TI  - A diffusion model-free framework with echo time dependence for free-water
      elimination and brain tissue microstructure characterization.
AB  - PURPOSE: The compartmental nature of brain tissue microstructure is typically
      studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI
      relies on signal representations or biophysical models, while MR relaxometry and
      correlation studies are based on regularized inverse Laplace transforms (ILTs).
      Here we introduce a general framework for characterizing microstructure that does
      not depend on diffusion modeling and replaces ill-posed ILTs with blind source
      separation (BSS). This framework yields proton density, relaxation times, volume
      fractions, and signal disentanglement, allowing for separation of the free-water
      component. THEORY AND METHODS: Diffusion experiments repeated for several
      different echo times, contain entangled diffusion and relaxation compartmental
      information. These can be disentangled by BSS using a physically constrained
      nonnegative matrix factorization. RESULTS: Computer simulations, phantom studies,
      together with repeatability and reproducibility experiments demonstrated that BSS
      is capable of estimating proton density, compartmental volume fractions and
      transversal relaxations. In vivo results proved its potential to correct for free
      water contamination and to estimate tissue parameters. CONCLUSION: Formulation of
      the diffusion-relaxation dependence as a BSS problem introduces a new framework
      for studying microstructure compartmentalization, and a novel tool for free-water
      elimination.

PMID- 29573011
TI  - Is age of menarche among school girls related to breastfeeding during infancy?
AB  - OBJECTIVES: Breastfeeding has been linked to various disease conditions in
      adulthood. Age of menarche has been proposed to be an intermediary factor on the
      life-course path to these disease conditions, but the link between breastfeeding
      and age of menarche remains under debate. This study aimed to investigate the
      association between age of menarche and breastfeeding during infancy. METHODS: A
      cross-sectional study was conducted in which 775 female high school students were
      randomly selected from private and public high schools in all provinces in
      Kuwait. Data on age of menarche were collected by self-administered
      questionnaires from the students, while data on breastfeeding were collected from
      their mothers through telephone interviews. Multiple linear regression was used
      to investigate the association between breastfeeding and age of menarche after
      adjusting for potential confounders. RESULTS: Of the study group 496 mothers
      responded to the telephone interview. Duration of breastfeeding was not
      significantly associated with age of menarche before or after adjusting for
      potential confounders (P = .279 and P = .124 for crude and fully adjusted model,
      respectively). Similarly, no significant association was found between type of
      breastfeeding during the first four months of life and age of menarche before or
      after adjusting for potential confounders (P = .949 and P = .398 for crude and
      fully adjusted model, respectively). CONCLUSION: No significant association was
      found between age of menarche and breastfeeding during infancy, which may suggest
      that the link between breastfeeding and disease conditions in adulthood is not
      necessarily mediated through age of menarche.

PMID- 29573012
TI  - Telehealth-based model of care redesign to facilitate local fitting and
      management of patients with a spinal fracture requiring a thoracic lumbar sacral
      orthosis in rural hospitals in New South Wales.
AB  - OBJECTIVE: To develop and implement a telehealth-based model of care for spinal
      fractures requiring management with thoracic lumbar sacral orthoses that
      eliminates the need for transfer to a metropolitan tertiary referral hospital.
      DESIGN: Pre-post design observational study evaluating model of care
      implementation. SETTING: Rural referral hospitals in a large NSW region covering
      metropolitan, rural and remote hospitals. PARTICIPANTS: Patients presenting with
      a thoracic or lumbar spine fracture requiring thoracic lumbar sacral orthoses
      management and rural clinicians caring for them. OUTCOME MEASURES: Number of
      patients managed in rural hospitals without transfer to a metropolitan tertiary
      referral hospital; length of stay and related cost efficiencies; clinicians'
      perceived skills, knowledge and confidence levels. RESULTS: Model of care was
      implemented with clinical and system governance processes; and educational
      workshops across eight rural hospitals. A total of 81 patients managed in rural
      hospitals under this model between July 2013 and June 2016 without transfer were
      included in this study. Mean length of stay reduced from nine to four days.
      Hospital transfers were eliminated from the patient journey, totalling 24 324 km.
      Workshops were attended by 71 clinicians from nine rural hospitals and survey
      findings indicated a significant increase in staff knowledge, skill and
      confidence post education. Cost efficiencies were gained by eliminating 162 inter
      hospital transfers and 405 patient bed days. CONCLUSION: This model has
      streamlined patient journeys and reduced transfers and travel, enabling rural
      clinicians to provide specialised services in local communities and facilitating
      timely evidence-based care in local communities without any adverse events.

PMID- 29573013
TI  - Policy to practice: Investment in transitioning new graduate nurses to the
      workplace.
AB  - AIM: To analyse nurses' perceptions of the impact of an extended transition
      programme on key dimensions of care delivery 1-6 years after graduation. The
      dimensions included decision-making, communication, care management, system
      integration and commitment. BACKGROUND: Health care employers in Ontario, Canada,
      can apply for government funding to support an extended transition programme for
      new graduate nurses that includes orientation and mentorship. METHODS: A cross
      sectional study design was used. Nurses who participated in the transition
      programme were compared with nurses who did not. A survey was administered to a
      convenience sample of 2369 nurses. RESULTS: There were statistically significant
      differences between the two groups. Nurses in the transition programme had higher
      mean scores on the key dimensions of care delivery. Results were confirmed when
      controlling for length of time since graduation. CONCLUSION: Extended transition
      benefits new graduate nurses. It has a lasting effect over time and impacts key
      dimensions of care delivery. It can also enhance workforce integration and reduce
      turnover. IMPLICATIONS FOR NURSING MANAGEMENT: Responding to the needs of new
      graduate nurses has potential long-term advantages for health care organisations
      and can influence both quality and delivery of care.

PMID- 29573014
TI  - A modified Continuous Quality Improvement approach to improve culturally and
      socially inclusive care within rural health services.
AB  - BACKGROUND: The sickest Australians are often those belonging to non-privileged
      groups, including Indigenous Australians, gay, lesbian, bisexual, transsexual,
      intersex and queer people, people from culturally and linguistically diverse
      backgrounds, socioeconomically disadvantaged groups, and people with disabilities
      and low English literacy. These consumers are not always engaged by, or included
      within, mainstream health services, particularly in rural Australia where health
      services are limited in number and tend to be generalist in nature. OBJECTIVE:
      The aim of this study was to present a new approach for improving the
      sociocultural inclusivity of mainstream, generalist, rural, health care
      organisations. DESIGN: This approach combines a modified Continuous Quality
      Improvement framework with Participatory Action Research principles and
      Foucault's concepts of power, discourse and resistance to develop a change
      process that deconstructs the power relations that currently exclude marginalised
      rural health consumers from mainstream health services. It sets up processes for
      continuous learning and consumer responsiveness. RESULTS: The approach proposed
      could provide a Continuous Quality Improvement process for creating more
      inclusive mainstream health institutions and fostering better engagement with
      many marginalised groups in rural communities to improve their access to health
      care. CONCLUSION: The approach to improving cultural inclusion in mainstream
      rural health services presented in this article builds on existing initiatives.
      This approach focuses on engaging on-the-ground staff in the need for change and
      preparing the service for genuine community consultation and responsive change.
      It is currently being trialled and evaluated.

PMID- 29573015
TI  - A balanced approach to falls prevention: Application in the real world.
AB  - BACKGROUND: Falls place a heavy burden on the health system, impacting on an
      individual's quality of life, often resulting in a fear of falling, reduction in
      independence and at times admission to residential care. This study aimed to
      determine health professionals' confidence in discussing falls prevention
      strategies, topics discussed and the barriers and enablers to falls prevention
      discussions with clients aged 60 years and over. METHOD: A cross-sectional self
      complete online survey was undertaken with a sample of health professionals (n =
      191) who had engaged in the services of the Stay On Your Feet(r) programs
      delivered by the Injury Matters in Western Australia (WA). RESULTS: The majority
      of participants were physiotherapists (25.7%), registered nurses (17.8%) and
      occupational therapists (11%) located in metropolitan (56%) and regional (44%)
      WA. Most health professionals (80.2%) were "highly" confident discussing falls
      prevention strategies. Discussion of falls prevention included the benefits of
      strength and balance exercises (83%), eating a healthy diet (78.7%), regular
      eyesight checks (64.5%), reviewing medications (54.8%) and exposure to sunlight
      (50.3%). The main enablers to falls prevention were knowledge (89.7%), skills to
      identify (77.7%) and implement (66.3%) falls prevention strategies, and access to
      printed resources (74.9%), while the main barrier was appointment times (14.6%).
      CONCLUSION: Health professionals' indicated that they are confident in discussing
      falls prevention strategies, and although a range of falls prevention strategies
      were discussed, limited attention was directed at the pharmacists' review of
      medications, eyesight checks and increasing vitamin D levels. SO WHAT?: Health
      professionals are discussing falls prevention strategies with their clients. A
      more multifaceted approach should be encouraged with an emphasis on all
      prevention strategies.

PMID- 29573016
TI  - Depressive symptoms, social anxiety, and perceived neck function in patients with
      head and neck cancer.
AB  - BACKGROUND: This study examined the relationships of depressive symptoms and
      social anxiety with perceived neck function in patients treated for head and neck
      cancer. METHODS: Depressive symptoms, social anxiety, and perceived neck-related
      function were measured at baseline, posttreatment, every 6 weeks thereafter for 1
      year after the end of treatment, and at 15 and 18 months posttreatment. Group
      based trajectory modeling was used to generate clusters of patients with similar
      baseline and trajectories of perceived neck-related function after head and neck
      cancer treatment. RESULTS: Participants included 83 subjects who had completed at
      least 1 follow-up assessment. Three clusters of longitudinal patterns in neck
      disability were identified: none/mild, moderate, and severe. Significant
      associations were found between membership in the neck disability index
      trajectories and membership in the longitudinal patterns of depressive symptoms
      and social anxiety. CONCLUSION: Impaired physical function and psychological
      distress are intertwined for patients with head and neck cancer long after
      completing treatment.

PMID- 29573017
TI  - Constructing health capital in ecological systems: A qualitative evaluation of
      community-based health workshops in the refugee community.
AB  - Refugee communities face numerous health and mental health concerns both during
      and after resettlement. Health issues, already deteriorated by chronic poverty,
      malnutrition and poor living conditions, are exacerbated by acculturative
      challenges, such as cultural and language barriers, stigma, and lack of resources
      and information. Since such needs in refugee communities affect both individual
      and collective capacity, it is important to consider policy environment and
      socioecological contexts for cultural adjustment and community resources for
      navigating systems, rather than individual health behaviours and communication
      skills only. To expand our understanding of health promotion capacity and
      resources, a broad and context-dependent concept will be necessary. Adopting a
      concept of health capital, this study aims to explore the impact of community
      based health workshops, while expanding and redefining the framework in the
      context of health promotion efforts for the refugee community in resettlement. As
      part of community-based participatory research, this qualitative study conducted
      seven focus group discussions (FGDs) with 22 Bhutanese refugees in 2014. Using a
      hybrid thematic analysis, themes emerged from the FGD data were organised and
      categorised into health capitals in ecological systems. The participants reported
      enhanced confidence and capacity for health promotion at individual, family and
      community levels. Given the interdependent coping and lifestyles of refugee
      communities, impacts on the participants' interactions and relations with family
      and community were significant, which emphasises the importance of assessment of
      interventions beyond an individualistic approach. The findings of this study
      underscore the vital role of varied forms of health capital in promoting health
      in the refugee community and connecting members to needed health resources and
      information. Health capital is an old and yet still new concept with a great
      potential to broaden our understanding of health resources by elaborating the
      impacts and interactions in individuals, family and community for health
      promotion.

PMID- 29573018
TI  - Participatory redesign of work organisation in hospital nursing: A study of the
      implementation process.
AB  - AIMS: The main goal of the study was to apply and analyse a moderated
      participatory small-group procedure with registered nurses, which aims at the
      development and implementation of measures to improve work organisation in
      hospital wards and nursing units. BACKGROUND: Participation in job redesign is an
      essential prerequisite of the successful implementation of improvement measures
      in nursing. METHODS: The study was carried out in a public hospital of maximum
      care in Germany. We selected 25 wards with the most critical reported exhaustion
      and general health and applied a series of moderated small-group sessions in
      which the registered nurses jointly identified deficits in their work
      organisation, developed improvement measures, and then implemented and assessed
      them. RESULTS: Registered nurses of 22 wards actively took part in the small
      group procedure. All nursing units jointly identified organisational deficits,
      developed possible improvement measures, and implemented them. The nursing teams
      then evaluated the implemented measures which were already assessable at the end
      of our research period; nearly all (99.0%) showed improvements, while 69.4%
      actually attained the desired goals. CONCLUSION: Participatory small-group
      activities may be successfully applied in hospital nursing in order to improve
      work organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Participatory assessment
      and redesign of nurses' work organisation should be integrated into regular team
      meetings. The nursing management should actively support the implementation
      process.

PMID- 29573019
TI  - Patient and family description of receiving care in acuity adaptable care model.
AB  - AIM: To explore patient and family perspectives of hospital care in an acuity
      adaptable care model implemented in an urban, public safety-net hospital.
      BACKGROUND: Specialty care units result in reactionary bed management. Changes in
      acuity generate costly, disruptive, intra-hospital patient transfers, which
      negatively affect clinical outcomes while increasing nurse workload. The acuity
      adaptable care model is a universal bed model structured to support patients in
      one room while providing staff, equipment and other resources across varying
      levels of acuity. METHOD: Qualitative descriptive methods were used to analyse
      the narratives of a purposive sample of patients and family members about
      receiving care in an acuity adaptable care delivery model. RESULTS: Three content
      areas emerged from the narratives and were categorized as feeling safe,
      perceiving continuity of care and valuing family, which culminated in a sense of
      comfort and healing while in the hospital. CONCLUSION: By bringing care services
      to the patient instead of taking the patient to the services, the acuity
      adaptable care model facilitated a perception of a healing environment for
      patients and family members. IMPLICATIONS FOR NURSING MANAGEMENT: The acuity
      adaptable care model should be considered when hospital facilities are undergoing
      major renovation or replacement.

PMID- 29573020
TI  - Adolescents drink less: How, who and why? A review of the recent research
      literature.
AB  - ISSUES: Today's teenagers have been described as a sober generation and we asked:
      'What is known about the recent decline in youth drinking?' APPROACH: A
      literature review (2005-2017). KEY FINDINGS: Research from wealthier parts of the
      world provides solid evidence of less alcohol use by youth since the millennium
      shift. Some studies show that this is reflected at all levels of consumption, but
      there are also indications that the heaviest drinkers have not reduced their
      drinking. The decrease is predominately seen in underage youth, and has been
      larger for boys than for girls in several countries. Teenagers across social
      strata drink less, but some disadvantaged subgroups have not followed the
      downward trend. Underage drinkers have apparently not become a more deviant group
      as the prevalence of drinking has dropped, indicating no hardening of the group.
      The major gap in the literature pertains to the issue of underlying driving
      forces. We found no evidence in support of the widespread assumption that the
      digital revolution has been of importance. A decline in parenting practices that
      are conductive to underage drinking has occurred in several countries, but
      studies examining whether these changes have contributed to less alcohol use by
      youth are almost non-existent. IMPLICATIONS: To inform alcohol policy and
      prevention, it is imperative to find out why teenage drinking has decreased in a
      fairly consistent way across numerous countries. CONCLUSION: Future research into
      the issue of falling prevalence rates of youth drinking should focus on possible
      explanatory factors at the population level rather than at the individual level.

PMID- 29573021
TI  - Manipulation of parental nutritional condition reveals competition among family
      members.
AB  - Parental care is thought to be costly, as it consumes time and energy. Such costs
      might be reduced in animal parents that raise their young on valuable food
      sources such as dung or carcasses, as parents are able to invest in self
      maintenance by feeding from the same resource. However, this might lower the
      nutritional value for other family members and, as a consequence, food
      competition might arise. To promote our understanding of the outcome of such
      competition, we manipulated the necessity of parents to feed from the resource.
      Using a full factorial design, we paired food-deprived or well-fed males with
      food-deprived or well-fed females of burying beetles, which are known to raise
      their young on vertebrate cadavers. We found that food-deprived parents consumed
      more of the carrion than those that were well-fed and this had a negative impact
      on other family members. However, the outcome of the competition depended on the
      sex of the parents, with females suffering when males fed more and offspring
      suffering when females fed more. Thus, family life involves selfish elements, as
      both parents remove resources for the purpose of self-maintenance. However,
      females show altruistic aspects, as they appear to restrict their food
      consumption for the benefit of their offspring when paired with a food-deprived
      male. Interestingly, males extend their stay with the brood when having faced
      food scarcity prior to reproduction, presumably to replenish their energy
      reserves. Our study therefore reveals that breeding on shared resources can
      promote family living, but also results in competition.

PMID- 29573022
TI  - Exploration of male urethral sphincter complex using diffusion tensor imaging
      (DTI)-based fiber-tracking.
AB  - BACKGROUND: Urinary incontinence is a major clinical problem arising primarily
      from age-related degenerative changes to the sphincter muscles. However, the
      precise anatomy of the normal male sphincter muscles has yet to be established.
      Diffusion tensor imaging (DTI) may offer a unique insight into muscle
      microstructure and fiber architecture. PURPOSE: To explore the anatomy of the
      urethral sphincter muscles pertinent to urinary continence function using DT-MRI.
      STUDY TYPE: Prospective cohort study. SUBJECTS: Eleven normal male subjects (mean
      age: 25.4 years); two subjects were scanned in three separate sessions to assess
      reproducibility. FIELD STRENGTH/SEQUENCE: 3T; using a diffusion-weighted spin
      echo planar sequence. ASSESSMENT: DT parameters including fractional anisotropy
      (FA), primary (lambda1 ), secondary (lambda2 ), and tertiary (lambda3 )
      eigenvalues, Apparent diffusion coefficient and radial diffusivity were analyzed
      statistically, while tracked muscle fibers were assessed visually. STATISTICAL
      TESTS: Regional differences (sphincters and longitudinal muscle of the urethra)
      in the DTI indices were assessed by one-way analysis of variance. A Tukey post
      hoc test was used to identify significant differences between muscle regions.
      RESULTS: Two sphincter muscles, one proximal near the base of the bladder,
      corresponding to the lisso-sphincter, and the other distal to the end of the
      prostate corresponding to the rhabdo-sphincter, surrounding a central urethral
      muscle fiber bundle, were clearly identified. FA was higher and lambda3 lower in
      the proximal sphincter muscle compared to the central urethral muscle and the
      distal sphincter (P < 0.05). The average coefficient of variation ranged from 5
      12% for the DTI indices. DATA CONCLUSION: Since DTI values are known to reflect
      underlying tissue microarchitecture, significant differences in DTI indices
      identified here between the muscles of the urethral complex may potentially arise
      from differences in tissue microarchitecture that may in turn be related to the
      specific function of the sphincter and other muscles. LEVEL OF EVIDENCE: 1
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1002-1011.

PMID- 29573023
TI  - Leadership style and organisational commitment among nursing staff in Saudi
      Arabia.
AB  - AIMS: To examine how nurse managers' leadership styles, and nurses'
      organisational commitment in Saudi Arabia relate. BACKGROUND: Effective
      leadership is influential in staff retention; however, recruiting and maintaining
      nurses is an increasing problem in Saudi Arabia. METHODS: Using a survey design,
      the Multifactor Leadership Questionnaire and the Organisational Commitment
      Questionnaire were distributed to a sample of 219 nurses and nurse managers from
      two hospitals in Saudi Arabia. RESULTS: Transformational leadership was the most
      dominant leadership style. After controlling for the influence of manager/staff
      status, nationality and hospitals, transformational leadership was the strongest
      contributor to organisational commitment. Perceptions of both transformational
      and transactional leadership styles, increased with age for nurse managers and
      nursing staff. CONCLUSION: Introducing the Full Range of Leadership model to the
      Saudi nursing workforce could help to prepare Saudi nurses for positions as nurse
      managers and leaders. IMPLICATIONS FOR NURSING MANAGEMENT: The study provides
      insight into the type of leadership that is best suited to the dynamic and
      changing health care system in Saudi Arabia. It is possible that transformational
      leaders could influence and induce positive changes in nursing.

PMID- 29573024
TI  - Barriers and facilitators to self-management of asthma in adolescents: An
      interview study to inform development of a novel intervention.
AB  - BACKGROUND AND OBJECTIVE: Despite literature that spans twenty years describing
      the barriers to asthma self-management in adolescents, successful, clinically
      based interventions to address this important issue are lacking. Given the
      limitations of some of the previous studies, we conducted a study that aimed to
      gain a broader insight into barriers and facilitators to self-management of
      asthma by adolescents, not just adherence to treatment, and triangulated their
      views with those of their parents and healthcare professionals. METHODS: Focus
      groups and interviews were conducted separately for 28 adolescents with asthma
      aged 12-18 years, 14 healthcare professionals and 12 parents. Focus groups and
      interviews were audio-recorded, and transcripts from each participant group were
      analysed separately using inductive thematic analysis. We triangulated the three
      perspectives by comparing themes that had emerged from each analysis. RESULTS:
      Adolescents', parents' and healthcare professionals' views were summarized into
      ten related themes that included forgetting and routines, knowledge,
      embarrassment and confidence, communication with healthcare professionals,
      triggers, support at school, apathy and taking responsibility. We found that
      adolescents, parents and healthcare professionals raised similar barriers and
      facilitators to self-management and our results provide further validation for
      previous studies. CONCLUSION AND CLINICAL RELEVANCE: Our study highlights that
      healthcare professionals may need to consider a range of psychological and
      contextual issues influencing adolescents' ability to effectively self-manage
      their asthma, in particular, how they implement treatment routines and the
      understanding that adolescents have of their condition and treatments. Crucially,
      healthcare professionals need to consider how this information is communicated
      and ensure they facilitate open, inclusive, two-way consultations. From this more
      comprehensive understanding, we have developed interventional strategies that
      healthcare professionals can utilize to empower adolescents to improve their
      asthma self-management.

PMID- 29573025
TI  - Should we look beyond Kt/V urea in assessing dialysis adequacy?
AB  - Since the advent of maintenance dialysis therapy, our interpretation of what
      adequate dialysis really is has broadened and become more controversial. This is
      not only due to our changing and aging dialysis population but also to our
      evolving knowledge base. As nephrologists, we strive to achieve both quality and
      (often) quantity of life for our patients and we feel reassured when we have a
      quantifiable marker to show for our efforts. However, we suggest that adequate
      dialysis reaches far beyond the realms of attaining a particular biochemical
      result. Dialysis adequacy should encompass a more comprehensive assessment of
      patient well-being. This metric could comprise quality of life and patient
      specified goals, sufficient small solute and middle molecule clearance, optimal
      blood pressure control, and effective bone-mineral balance, all in the context of
      minimizing mortality and morbidity, and a livable dialysis regimen for the
      patient.

PMID- 29573027
TI  - BRAFwild papillary thyroid carcinoma has two distinct mRNA expression patterns
      with different clinical behaviors.
AB  - BACKGROUND: Using a large set of genomic data from The Cancer Genome Atlas
      (TCGA), we classified BRAFwild papillary thyroid carcinomas (PTCs) into 2
      subtypes with distinct molecular patterns and different clinical behaviors. We
      also suggested gene signatures (RAS-score) to predict molecular subtypes and
      clinical behaviors of BRAFwild PTC. METHOD: Integrated genomic analysis was done
      using all genomic data of PTC in TCGA data portal (https://tcga-data.nci.nih.gov)
      and cancer browser (https://genome-cancer.ucsc.edu). Using Gene Ontology and a
      logistic regression test, we selected gene signatures (RAS-score) and applied
      this prediction model to the validation cohort (GSE60542). RESULT: When we
      performed multiplatform genomic analysis, BRAFwild PTCs were divided into 2
      molecular subtypes. Each subtype showed distinct molecular patterns and clinical
      behaviors. Gene signatures successfully predicted molecular subtype in another
      validation cohort. CONCLUSION: We found that BRAFwild PTCs were divided into 2
      molecular subtypes and each subtype showed distinct molecular patterns, different
      activated pathways, and different clinical behaviors.

PMID- 29573026
TI  - Neural correlates of reduced depressive symptoms following cognitive training for
      chronic traumatic brain injury.
AB  - Depression is the most frequent comorbid psychiatric condition among individuals
      with traumatic brain injury (TBI). Yet, little is known about changes in the
      brain associated with reduced depressive symptoms following rehabilitation for
      TBI. We identified whether cognitive training alleviates comorbid depressive
      symptoms in chronic TBI (>6 months post-injury) as a secondary effect. Further,
      we elucidated neural correlates of alleviated depressive symptoms following
      cognitive training. A total of seventy-nine individuals with chronic TBI (53
      depressed and 26 non-depressed individuals, measured using the Beck Depressive
      Inventory [BDI]), underwent either strategy- or information-based cognitive
      training in a small group for 8 weeks. We measured psychological functioning
      scores, cortical thickness, and resting-state functional connectivity (rsFC) for
      these individuals before training, immediately post-training, and 3 months post
      training. After confirming that changes in BDI scores were independent of
      training group affiliation, we identified that the depressive-symptoms group
      showed reductions in BDI scores over time relative to the non-depressed TBI
      controls (p < .01). Within the depressive-symptoms group, reduced BDI scores was
      associated with improvements in scores for post-traumatic stress disorder, TBI
      symptom awareness, and functional status (p < .00625), increases in cortical
      thickness in four regions within the right prefrontal cortex (pvertex  < .01,
      pcluster <.05), and decreases in rsFC with each of these four prefrontal regions
      (pvertex  < .01, pcluster  < .0125). Overall, these findings suggest that
      cognitive training can reduce depressive symptoms in TBI even when the training
      does not directly target psychiatric symptoms. Importantly, cortical thickness
      and brain connectivity may offer promising neuroimaging markers of training
      induced improvement in mental health status in TBI.

PMID- 29573028
TI  - Even when right is all that's left: There are still more options for recovery
      from aphasia.

PMID- 29573029
TI  - Place of surgery in the management of post-operative chronic pain after placement
      of prosthetic material based on a series of 107 cases.
AB  - AIMS: The objective of this study was to evaluate the efficacy of surgical
      removal of prosthetic material, possibly combined with nerve release, on chronic
      postoperative pain following placement of prosthetic material. MATERIAL AND
      METHODS: Single-tertiary-centre study on 107 patients managed between November
      2004 and April 2016 for removal of prosthetic material responsible for
      postoperative chronic pain: retropubic suburethral sling (n = 32), transobturator
      suburethral sling (n = 50), prolapse mesh (n = 16), and hernia mesh (n = 9). The
      primary endpoint was at least 50% reduction of pain evaluated by a pain numerical
      rating scale (NRS). RESULTS: The mean interval between the initial operation
      involving placement of prosthetic material and reoperation for removal of
      prosthetic material was 41.2 +/- 35.4 months. In all cases pain apperaed
      immediately following prosthetic material placement surgery. Pain presented
      neuropathic features in almost 30% of cases and was poorly systematized in more
      than one-half The mean follow-up of the study population was 8.4 +/- 10.3 months.
      The mean pain NRS score for the overall population was seven preoperatively and
      three at last follow-up. At least 50% reduction of the pain NRS score was
      observed 67% of cases at last follow-up. During follow-up, 45% of patients
      experienced relapse of the disorder for which the prosthetic material was
      initially placed with, in particular, a 62% recurrence rate of urinary
      incontinence after removal of transobturator suburethral tape. CONCLUSION:
      Surgical removal of prosthetic material to treat chronic postoperative pain,
      achieved global improvement of pain in about two-thirds of cases, but with a risk
      of recurrence of the initial disorders.

PMID- 29573030
TI  - Treatment course and its predictors in patients with somatoform disorders: A
      routine outcome monitoring study in secondary psychiatric care.
AB  - AIM: Somatoform disorders are common and often chronic. It would be helpful to
      distinguish those patients who are likely to have a positive treatment course
      from those who are likely to follow a negative course. Such studies of different
      somatoform disorders are scarce, especially in secondary psychiatric care. This
      study examined the 6-month treatment course of psychological, physical symptoms,
      and functioning, and its predictors in a naturalistic sample of secondary
      psychiatric care outpatients with somatoform disorders. METHOD: The present study
      used routine outcome monitoring data of patients with somatoform disorders
      regarding their 6-month treatment course of psychological and physical symptoms
      as well as functioning. The following patient groups were included: total group
      of somatoform disorders (N = 435), and undifferentiated somatoform disorder (N =
      242), pain disorder (N = 102), body dysmorphic disorder (N = 51), and
      hypochondriasis (N = 40). Measures were Mini-International Neuropsychiatric
      Interview plus, Brief Symptom Inventory, Montgomery-Asberg Depression Rating
      Scale, Brief Anxiety Scale, Short Form Health Survey 36, and Physical Symptom
      Checklist (PSC). RESULTS: The study population generally showed high co
      morbidity, especially with anxiety and mood disorders. The PSC total score, body
      dysmorphic disorder, and hypochondriasis were significant predictors for the
      treatment course of symptoms (Brief Symptom Inventory), whereas the PSC total
      score was the only significant predictor for the course of functioning (Short
      Form Health Survey 36). CONCLUSION: Secondary psychiatric care outpatients with
      somatoform disorders showed high co-morbidity with anxiety and mood disorders,
      and an unfavourable 6-month course of both symptoms and functioning. Clinical
      implications are discussed, such as additional treatment of co-morbidity in
      somatoform disorders.

PMID- 29573031
TI  - A systematic review of adverse events of rifapentine and isoniazid compared to
      other treatments for latent tuberculosis infection.
AB  - PURPOSE: Tuberculosis (TB) remains a common cause of death globally. A regimen of
      12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT-3) has
      recently been recommended by the World Health Organization for the treatment of
      latent TB infection (LTBI). We aimed to determine whether the INH/RPT-3 regimen
      had similar or lesser rates of adverse events compared to other LTBI regimens,
      namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and
      rifampin plus INH for 3 to 4 months. METHODS: We searched MEDLINE, Embase,
      CENTRAL, PubMed, ICTRP, clinicaltrials.gov, and Canadian Agency for Drugs and
      Technologies in Health's Gray Matters Light for randomized, postmarketing, and
      comparative nonrandomized studies of patients with confirmed LTBI that reported
      the frequency of at least 1 adverse event of relevance for a regimen of interest.
      The search included studies published until March 2017. The frequencies of
      adverse events were extracted and are presented descriptively. RESULTS: Data from
      23 randomized and 55 nonrandomized studies were included. Although inconsistent
      event reporting and high heterogeneity limited comparisons, the adverse event
      profile of INH/RPT-3 appeared generally favorable. Flu-like reactions were
      reported with an increased frequency and hepatotoxicity with a lower frequency
      than standard treatment. CONCLUSIONS: While INH/RPT-3 had an overall low
      frequency of adverse events compared to INH monotherapy, reporting of adverse
      events for many regimens was limited meaning results should be interpreted
      cautiously. Future studies of LTBI treatment would benefit from more complete
      collection and reporting of adverse events and more consistent definitions of
      hepatotoxicity.

PMID- 29573032
TI  - Visualizing the effects of metformin on tumor growth, vascularity, and metabolism
      in head and neck cancer.
AB  - BACKGROUND: The antidiabetic drug metformin (Met) is believed to inhibit tumor
      proliferation by altering the metabolism of cancer cells. In this study, we
      examined the effects of Met on tumor oxygenation, metabolism, and growth in head
      and neck squamous cell carcinoma (HNSCC) using non-invasive multimodal imaging.
      MATERIALS AND METHODS: Severe combined immunodeficient (SCID) mice bearing
      orthotopic FaDu HNSCC xenografts were treated with Met (200 mg/kg, ip) once daily
      for 5 days. Tumor oxygen saturation (%sO2 ) and hemoglobin concentration (HbT)
      were measured using photoacoustic imaging (PAI). Fluorescence imaging was
      employed to measure intratumoral uptake of 2-deoxyglucosone (2-DG) following Met
      treatment while magnetic resonance imaging (MRI) was utilized to measure tumor
      volume. Correlative immunostaining of tumor sections for markers of proliferation
      (Ki67) and vascularity (CD31) was also performed. RESULTS: At 5 days post-Met
      treatment, PAI revealed a significant increase (P < .05) in %sO2 and HbT levels
      in treated tumors compared to untreated controls. Fluorescence imaging at this
      time point revealed a 46% decrease in mean 2-DG uptake compared to controls. No
      changes in hemodynamic parameters were observed in mouse salivary gland tissue. A
      significant decrease in Ki-67 staining (P < .001) and MR-based tumor volume was
      also observed in Met-treated tumors compared to controls with no change in CD31 +
      vessel count following Met therapy. CONCLUSION: Our results provide, for the
      first time, direct in vivo evidence of Met-induced changes in tumor
      microenvironmental parameters in HNSCC xenografts. Our findings highlight the
      utility of multimodal functional imaging for non-invasive mapping of the effects
      of Met in HNSCC.

PMID- 29573034
TI  - Appropriate utilization of cardiac magnetic resonance for the assessment of heart
      failure and potential associated cost savings.
AB  - BACKGROUND: The rapid growth in cardiac imaging utilization has led to the
      development of appropriate use criteria (AUC) in an effort to control costs.
      Recently, cardiac MRI has developed into a valuable modality in the evaluation of
      cardiac disease. However, there are no studies examining the appropriate use of
      cardiac MRI in clinical practice. PURPOSE: To determine the appropriate
      utilization of cardiac MRI in a large quaternary care institution and to compare
      percentages of appropriate utilization pre- and postpublication of the AUC
      document. We hypothesized that percentages of appropriate cardiac MRI utilization
      will be similar to those of other comparable cardiac imaging modalities and that
      there would be a significant change in appropriate use pre- and post-AUC
      publication. STUDY TYPE: Retrospective cohort study. POPULATION: In all, 2032
      consecutive patients undergoing cardiac MRI for the assessment of heart failure
      between 2012-2016. FIELD STRENGTH: 1.5T. ASSESSMENT: Data were collected and an
      appropriateness category was assigned for each cardiac MRI. STATISTICAL TESTS:
      Rates of major cardiac risk factors were compared between those undergoing
      cardiac MRIs pre- and post-AUC using the chi-square and the Mann-Whitney tests
      for categorical and continuous variables, respectively. Appropriateness
      classification was compared pre- and post-AUC publication using the chi-square
      test. RESULTS: There were no significant differences in the prevalence of major
      cardiovascular risk factors before and after publication of the AUC. 95.5% of all
      cardiac MRIs were appropriate based on the AUC. Further, there was a significant
      difference when comparing the appropriateness classification before and after
      publication of the AUC (P = 0.0003), potentially associated with annual cost
      savings of ~$14.8 million. DATA CONCLUSION: We report a very high percentage of
      appropriate use of cardiac MRI and a significant increase in the proportion of
      tests classified as appropriate after AUC publication. LEVEL OF EVIDENCE: 3
      Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.

PMID- 29573033
TI  - Individualized immunoglobulin therapy in chronic immune-mediated peripheral
      neuropathies.
AB  - Despite the well-recognized importance of immunoglobulin therapy
      individualization during the treatment of chronic inflammatory demyelinating
      polyneuropathy (CIDP), the pathway to best achieve optimization is unknown. There
      are many pharmacokinetic and immunobiologic variables that can potentially
      influence the appropriateness of any individual therapy. Although identification
      of specific autoantibodies and their targets has only been accomplished in a
      minority of patients with CIDP, already the diagnostic and treatment implications
      of specific autoantibody detection are being realized. Individual variability in
      IgG pharmacokinetic properties including IgG catabolic rates and distribution, as
      well as the IgG level necessary for disease control also require consideration
      during the optimization process. For optimization to be successful there must be
      a measure of treatment response that has a clinically meaningful interpretation.
      There are currently available well-defined and validated clinical assessment
      tools and outcome measures that are well suited for this purpose. While there
      remains much to learn on how best to manipulate immunopathology and
      immunoglobulin pharmacokinetics in the most favorable way, there currently exists
      an understanding of these principles to a degree sufficient to begin to develop
      rational and evidence-based treatment optimization strategies.

PMID- 29573035
TI  - Synthesis and physicochemical studies of amyloidogenic hexapeptides derived from
      human cystatin C.
AB  - Human cystatin C (hCC) is a low molecular mass protein that belongs to the
      cystatin superfamily. It is an inhibitor of extracellular cysteine proteinases,
      present in all human body fluids. At physiological conditions, hCC is a monomer,
      but it has a tendency to dimerization. Naturally occurring hCC mutant, with
      leucine in position 68 substituted by glutamine (L68Q), is directly involved in
      the formation of amyloid deposits, independently of other proteins. This process
      is the primary cause of hereditary cerebral amyloid angiopathy, observed mainly
      in the Icelandic population. Oligomerization and fibrillization processes of hCC
      are not explained equally well, but it is proposed that domain swapping is
      involved in both of them. Research carried out on the fibrillization process led
      to new hypothesis about the existence of a steric zipper motif in amyloidogenic
      proteins. In the hCC sequence, there are 2 fragments which may play the role of a
      steric zipper: the loop L1 region and the C-terminal fragment. In this work, we
      focused on the first of these. Nine hexapeptides covering studied hCC fragment
      were synthesized, and their fibrillogenic potential was assessed using an array
      of biophysical methods. The obtained results showed that the studied hCC fragment
      has strong profibrillogenic propensities because it contains 2 fragments
      fulfilling the requirements for an effective steric zipper located next to each
      other, forming 1 super-steric zipper motif. This hCC fragment might therefore be
      responsible for the enhanced amyloidogenic properties of dimeric or partially
      unfolded hCC.

PMID- 29573037
TI  - Nonlinear resonances in linear segmented Paul trap of short central segment.

PMID- 29573036
TI  - Three-dimensional visualization of rat retina by X-ray differential phase
      contrast tomographic microscopy.
AB  - The retina is one of the most tiny and sophisticated tissues of the body. Three
      dimensional (3D) visualization of the whole retina is valuable both in clinical
      and research arenas. The tissue has been predominantly assessed by time-consuming
      histopathology and optical coherence tomography (OCT) in research and clinical
      arenas. However, none of the two methods can provide 3D imaging of the retina.
      The purpose of this study is to give a volumetric visualization of rat retina at
      submicron resolution, using an emerging imaging technique-phase-contrast X-ray
      CT. A Sprague-Dawley (SD) rat eye specimen was scanned with X-ray differential
      phase contrast tomographic microscopy (DPC-microCT) equipped at the Swiss Light
      Source synchrotron. After scanning, the specimen was subjected to routine
      histology procedures and severed as a reference. The morphological
      characteristics and signal features of the retina in the DPC-microCT images were
      evaluated. The total retina and its sublayers thicknesses were measured on the
      DPC-microCT images and compared with those obtained from the histological
      sections. The retina structures revealed by DPC-microCT were highly consistent
      with the histological section. In this study, we achieved nondestructive 3D
      visualization of SD rat retina. In addition to detailed anatomical structures,
      the objective parameters provided by DPC-microCT make it a useful tool for
      retinal research and disease diagnosis in the early stage.

PMID- 29573038
TI  - Conditioned pain modulation using painful cutaneous electrical stimulation or
      simply habituation?
AB  - BACKGROUND AND AIMS: Cold pressor test was recently reported to significantly
      reduce painful cutaneous electrical stimulation (PCES)-induced pain and
      corresponding evoked potentials (PCES-EPs), but whether this reduction is an
      effect of conditioned pain modulation (CPM) remains unknown. To what extent these
      findings are confounded by habituation is also unknown. We thus compared the
      effect of CPM and habituation on PCES-induced pain and PCES-EPs and analysed
      whether increased attention by a random change of electric stimulation would
      intensify this possible habituation effect. METHODS: Three custom-built
      concentric surface electrodes were used to induce a pain intensity of 60 on a 0
      100 numerical rating scale (NRS) among 29 healthy subjects (age 20-35y, 16
      females). PCES-EPs (including P0N1 and N1P1 amplitudes, N1 latencies) were
      assessed over Cz. Group A received 14 min of electrical stimulation with constant
      intensity followed by 14 min of electrical stimulation with variable intensities,
      group B vice versa. Afterwards, subjects perceived cold-water pain (10  degrees
      C) contralaterally as conditioning stimulus to assess CPM. Statistical analysis
      was conducted with ANOVA and t-test. RESULTS: In both groups, N1 latencies remain
      unchanged, but the intensity of PCES-induced pain (12 +/- 17%; p < 0.01) and N1P1
      amplitudes of PCES-EPs (10 +/- 16%; p < 0.05) decreased significantly during the
      14-min PCES with constant current intensity. CPM also significantly reduced pain
      ratings (36 +/- 19%; p < 0.001) and amplitudes (37.2 +/- 15.8%), p < 0.001). A
      significant decline of P0N1 amplitudes occurred only during CPM (18 +/- 61%; p <
      0.001). CONCLUSION: We found a significant effect of habituation on PCES-induced
      pain and PCES-EPs, although the effect of CPM was significantly larger and could
      not be explained by habituation alone. SIGNIFICANCE: Painful cutaneous electrical
      stimulation leads to moderate habituation of pain and evoked potential
      amplitudes, but the conditioned pain modulation effect using this method is
      significantly larger, which might indicate a different mechanism in central
      processing.

PMID- 29573039
TI  - Tubular dentin sealer penetration after different final irrigation protocols: A
      confocal laser scanning microscopy study.
AB  - The aim of this study was to evaluate tubular dentin sealer penetration,
      comparing different final irrigation protocols using a conventional needle
      (CONV), EndoActivator system (EAS), EndoVac system (EVS), and ultrasound (PUI).
      Initially, fifty-two first maxillary molars with a single canal in the palatal
      root, without abrupt curvatures, resorptive processes, or previous endodontic
      treatment were selected for this study. Then, the crowns were sectioned to obtain
      palatal roots 15 mm in length. The root canals were prepared with the ProTaper
      Universal System and irrigated with 5% NaOCl. Afterwards, the specimens were
      divided into four groups (n. 13), according to the final irrigation protocol:
      CONV, EAS, EVS, and PUI. After filling, slices at 3 mm and 5 mm from the apex
      were obtained for analysis by confocal laser scanning microscopy. Two-way
      comparisons between the groups and the levels were performed with Games Howell's
      test (p < .05). Tubular dentin sealer penetration was higher at 5 mm compared
      with 3 mm from the apex (p < .05). The EAS group showed a higher percentage of
      tubular dentin sealer penetration, compared with the CONV group, at both levels.
      At 3 mm, there was no statistically significant difference among EAS, EVS, and
      PUI; however, these groups showed better performance, compared with the CONV
      group. At 5 mm, there was no statistically significant difference between the EAS
      and EVS groups, but both showed higher sealer penetration than the PUI group (p <
      .05). The EAS and EVS groups achieved better degrees of tubular dentin sealer
      penetration, compared with the other groups.

PMID- 29573040
TI  - F463L increases the potential of dofetilide on human ether-a-go-go-related gene
      (hERG) channels.
AB  - Mutations in genes related to long QT syndrome (LQTS) is recognized as an
      independent risk of drug-induced LQTS. We previously screened a mutation F463L in
      a Chinese patient with LQT2, syncope, and epilepsy. Here, we planned to
      illustrate how F463L influences the action of dofetilide on hERG channels. F463L
      hERG plasmids were transfected into the stable Human Embryonic Kidney 293
      (HEK293) cells expressing WT-hERG to generate heterozygous mutant (WT + F463L
      hERG). Whole-cell patch clamp and laser confocal scanning microscopy were used to
      evaluate electrophysiological consequences and the membrane distribution of hERG
      protein. In comparison of WT-hERG channels exposed to dofetilide, heterozygous
      F463L-hERG channels showed a reduction in the density of tail currents when
      exposed amidarone. F463L-hERG also altered the action of dofetilide on the gating
      properties of hERG channels. Images of dofetilide-treated cells expressing
      heterozygous F463L showed a severe retention and reduction of protein expression
      on the membrane compared to WT. In conclusion, dofetilide displays a powerful
      inhibitory effect on the currents from cells expressing heterozygous F463L, thus
      showing an additive suppression of currents by F463L with dofetilide.

PMID- 29573041
TI  - APOE influences working memory in non-demented elderly through an interaction
      with SPON1 rs2618516.
AB  - Exploring how risk genes cumulatively impair brain function in preclinical phase
      (i.e., in cognitively normal elderly) could provide critical insights into the
      pathophysiology of Alzheimer's disease (AD). Working memory impairment has always
      been a considerable cognitive deficit in AD, which is likely under complex
      genetic control. Though, the APOE E4 allele could damage the working memory
      performance in normal elderly, dissociable results have been reported. This
      allele may exert specific effects in contexts with other genetic variants. The
      rs2618516 in the spondin 1 gene (SPON1) has been associated with AD risk and
      brain structure in the elderly. SPON1 may interact with APOE through processing
      the amyloid precursor protein and suppressing amyloid-beta levels. Using
      neuropsychological tasks from 710 individuals, we found significant SPON1 * APOE
      genotype interactions in working memory and executive function performances.
      Moreover, such interaction was also found in regional brain activations based on
      functional magnetic resonance imaging data with the n-back working memory task
      performed in a sub-cohort of 64 subjects. The effects of E4 allele on activation
      of right inferior frontal gyrus, triangular part (IFGtriang.R) were modulated by
      rs2618516 in a working memory task. Furthermore, lower IFGtriang.R activation was
      associated with better cognitive functions. Moreover, the IFGtriang.R activation
      could mediate the impacts of SPON1 * APOE interactions on working memory
      performance. These findings suggested the importance of weighing APOE effects on
      brain activation under the working memory task within the context of the SPON1
      genotype.

PMID- 29573042
TI  - Value of diffusion kurtosis imaging in assessing low-grade gliomas.
AB  - BACKGROUND: Diffusion kurtosis imaging (DKI) measures have been shown to provide
      increased sensitivity relative to diffusion tensor imaging (DTI) in detecting
      pathologies. PURPOSE: To compare the sensitivity of DKI-derived kurtosis and
      diffusion maps for assessment of low-grade gliomas (LGG). STUDY TYPE: Prospective
      study. POPULATION: In all, 19 LGG patients and 26 healthy control subjects were
      recruited. FIELD STRENGTH/SEQUENCE: Echo-planar-imaging diffusion-weighted MR
      images (b-values = 0, 1000, and 2000 with 30 diffusion gradient directions) were
      acquired on a 3T scanner. ASSESSMENT: Maps for mean, axial, and radial
      diffusivity (MD, AD, and RD) and kurtosis (MK, AK, and RK), and fractional
      anisotropy (FA) were evaluated in the tumor, perilesional white matter, and
      contralateral normal-appearing white matter regions. STATISTICAL TESTING: General
      linear models (GLM), Cohen's d for effect size estimates, false discovery rate
      (FDR) for multiple corrections, Cochran Q-test. RESULTS: Pairwise differences
      were observed for all diffusion and kurtosis measures between the studied regions
      (FDR P < 0.001), except an FA map that failed to show significant differences
      between the lesion and perilesional white matter (FDR P = 0.373). Effect size
      analysis showed that kurtosis metrics were found to be 18.8% (RK, P = 0.144) to
      29.1% (AK, P < 0.05) more sensitive in discriminating perilesional regions from
      the lesion than corresponding diffusion metrics, whereas AK provided a 25.0% (P <
      0.05) increase in sensitivity in discriminating perilesional and contralateral
      white matter. RK was found to be the most sensitive to contralateral white matter
      differences between low-grade gliomas and controls, with MK and RK providing a
      significantly greater sensitivity of 587.2% (P < 0.001) and 320.7% (P < 0.001)
      than MD and RD, respectively. DATA CONCLUSION: Kurtosis maps showed increased
      sensitivity, as compared to counterpart diffusion maps, for evaluation of
      microstructural changes in gliomas with a 3-6-fold increment in assessing changes
      in contralateral white matter. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3
      J. Magn. Reson. Imaging 2018;48:1551-1558.

PMID- 29573043
TI  - Compound heterozygosity for loss-of-function FARSB variants in a patient with
      classic features of recessive aminoacyl-tRNA synthetase-related disease.
AB  - Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes that ligate
      amino acids onto tRNA molecules. Genes encoding ARSs have been implicated in
      phenotypically diverse dominant and recessive human diseases. The charging of
      tRNAPHE with phenylalanine is performed by a tetrameric enzyme that contains two
      alpha (FARSA) and two beta (FARSB) subunits. To date, mutations in the genes
      encoding these subunits (FARSA and FARSB) have not been implicated in any human
      disease. Here, we describe a patient with a severe, lethal, multisystem,
      developmental phenotype who was compound heterozygous for FARSB variants:
      p.Thr256Met and p.His496Lysfs*14. Expression studies using fibroblasts isolated
      from the proband revealed a severe depletion of both FARSB and FARSA protein
      levels. These data indicate that the FARSB variants destabilize total
      phenylalanyl-tRNA synthetase levels, thus causing a loss-of-function effect.
      Importantly, our patient shows strong phenotypic overlap with patients that have
      recessive diseases associated with other ARS loci; these observations strongly
      support the pathogenicity of the identified FARSB variants and are consistent
      with the essential function of phenylalanyl-tRNA synthetase in human cells. In
      sum, our clinical, genetic, and functional analyses revealed the first FARSB
      variants associated with a human disease phenotype and expand the locus
      heterogeneity of ARS-related human disease.

PMID- 29573045
TI  - Bioinspired Design of Fe3+ -Doped Mesoporous Carbon Nanospheres for Enhanced
      Nanozyme Activity.
AB  - Nanozymes have received considerable attention as alternatives of natural
      enzymes. However, the catalytic activity of nanozymes is often lower than that of
      natural enzymes, which largely limits their applications. Current methods
      utilized to improve the catalytic efficiency and substrate selectivity of a
      nanozyme usually have some inherent drawbacks. Herein, a biomimetic strategy was
      developed to design Fe3+ -doped mesoporous carbon nanospheres (Fe3+ -MCNs) as a
      horseradish peroxidase (HRP) mimic to realize the structure and function
      mimicking of natural HRP. In this system, Fe3+ ions could act as catalytic
      centers and carboxyl-modified mesoporous carbon nanospheres (MCNs-COOH) could be
      used to bind with substrates. As a result, Fe3+ -MCNs showed higher enzymatic
      activity than that of Fe3 O4 nanoparticles. Therefore, this strategy can
      contribute to the development of nanozymes and further understanding of the
      complicated enzymatic reactions in natural and biological systems.

PMID- 29573044
TI  - Missing data in trial-based cost-effectiveness analysis: An incomplete journey.
AB  - Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide
      key evidence for informing healthcare decision making, but missing data pose
      substantive challenges. Recently, there have been a number of developments in
      methods and guidelines addressing missing data in trials. However, it is unclear
      whether these developments have permeated CEA practice. This paper critically
      reviews the extent of and methods used to address missing data in recently
      published trial-based CEA. Issues of the Health Technology Assessment journal
      from 2013 to 2015 were searched. Fifty-two eligible studies were identified.
      Missing data were very common; the median proportion of trial participants with
      complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most
      common approach for the primary analysis was to restrict analysis to those with
      complete data (43%), followed by multiple imputation (30%). Half of the studies
      conducted some sort of sensitivity analyses, but only 2 (4%) considered possible
      departures from the missing-at-random assumption. Further improvements are needed
      to address missing data in cost-effectiveness analyses conducted alongside
      randomised trials. These should focus on limiting the extent of missing data,
      choosing an appropriate method for the primary analysis that is valid under
      contextually plausible assumptions, and conducting sensitivity analyses to
      departures from the missing-at-random assumption.

PMID- 29573047
TI  - A randomized controlled trial of a group intervention for siblings of children
      with cancer: Changes in symptoms of anxiety in siblings and caregivers.
AB  - OBJECTIVE: This study assessed the effects of a group intervention-Siblings
      Coping Together (SibCT)-on siblings' and caregivers' anxiety symptoms compared to
      controls, and potential moderators. METHODS: Seventy healthy siblings of children
      on or off treatment (7-16 y old, 41 males) participated in a randomized
      controlled trial (RCT) with 2 arms/groups: SibCT (n = 41) and an attention
      control (CG) (n = 34). Both groups had eight 2-hour weekly sessions. EG followed
      SibCT's educational, social, and problem-solving activities. CG had planned games
      and crafts. Siblings and caregivers self-reported on anxiety symptoms at
      baseline, intervention end, and 3 months later. Multivariable mixed model
      analyses examined the intervention effect over time, and potential moderators
      (gender, on/off ill child's treatment). RESULTS: No main effects of group or time
      were found in sibling scores. A group * gender interaction (P < .05) indicated
      that in the intervention group female siblings reported less total anxiety
      symptoms than male siblings, with no significant gender differences in the
      control group. Caregivers' total anxiety symptoms declined over time (P < .02). A
      group * on/off treatment interaction in physiological/panic subscale (P < .03)
      indicated that when ill child was on treatment, caregivers of siblings in SibCT
      reported less anxiety compared with caregivers of CG. CONCLUSIONS: There was no
      clear SibCT intervention effect. SibCT may benefit female siblings, and
      caregivers whose ill child is on active treatment. Contextual factors (gender)
      seem to influence psychosocial intervention in this population.

PMID- 29573046
TI  - Meta-analytic evidence for altered mesolimbic responses to reward in
      schizophrenia.
AB  - Dysfunction of reward-related neural circuitry in schizophrenia (SCZ) has been
      widely reported, and may provide insight into the motivational and cognitive
      disturbances that characterize the disorder. Although previous meta-analyses of
      reward learning paradigms in SCZ have been performed, a meta-analysis of whole
      brain coordinate maps in SCZ alone has not been conducted. In this study, we
      performed an activation likelihood estimate (ALE) meta-analysis, and performed a
      follow-up analysis of functional connectivity and functional decoding of
      identified regions. We report several salient findings that extend prior work in
      this area. First, an alteration in reward-related activation was observed in the
      right ventral striatum, but this was not solely driven by hypoactivation in the
      SCZ group compared to healthy controls. Second, the region was characterized by
      functional connectivity primarily with the lateral prefrontal cortex and pre
      supplementary motor area (preSMA), as well as subcortical regions such as the
      thalamus which show structural deficits in SCZ. Finally, although the meta
      analysis showed no regions outside the ventral striatum to be significantly
      altered, regions with higher functional connectivity with the ventral striatum
      showed a greater number of subthreshold foci. Together, these findings confirm
      the alteration of ventral striatal function in SCZ, but suggest that a network
      based approach may assist future analysis of the functional underpinnings of the
      disorder.

PMID- 29573048
TI  - Rehabilitation of Edentulism and Mortality: A Systematic Review.
AB  - PURPOSE: It has been shown that tooth loss is associated with an increased risk
      of early mortality, and that prosthetic rehabilitation of edentulism improves
      quality of life and reduces morbidity. This review examines association between
      prosthetic rehabilitation of the edentulous state with a complete denture and
      mortality. METHODS: A systematic search using combinations of related keywords
      for "complete denture" and "mortality" was performed on PubMed, Web of Science,
      and Google Scholar. A reference search of included articles and author contacts
      was also performed. RESULTS: None of the studies reported results for association
      between mortality and wearing complete dentures among edentulous individuals;
      however, based on the published methods and results, a total of 15 studies were
      found to be eligible for author contacts to obtain relevant data. Overall, 5
      eligible studies were included and critically evaluated to summarize their
      findings. The follow-up period in these studies ranged from 3 to 24 years, and
      the age group of included samples ranging from 52 to 105 years. The proportion of
      individuals not wearing dentures ranged from 3.0% to 13.3%. Four of the included
      studies showed fewer individuals without complete dentures surviving over the
      follow-up years as compared to the group wearing complete dentures. One of two
      studies that could adjust for certain confounders found no significant difference
      in mortality after adjusting, but another study found a 42% reduced risk of dying
      among those wearing complete dentures, as compared to those not wearing complete
      dentures after adjusting for age, sex, educational level, smoking, alcohol
      drinking, body mass index, time spent walking daily, medical history,
      psychological distress score, energy intake, and protein intake. Due to the small
      sample size of nondenture wearers, it was not possible to analyze with
      statistical rigor the comparative risk of dying associated with wearing or not
      wearing complete dentures. CONCLUSION: Most of the included studies indicated a
      higher proportion of deceased edentulous patients not using dentures as compared
      to denture wearers. Nevertheless, small sample size prevents a definite
      conclusion being drawn regarding a relationship between prosthetic rehabilitation
      and mortality among edentulous individuals.

PMID- 29573049
TI  - Hemoglobin Seattle detection based on low capillary oxygen saturation: First
      reported case in Japan.

PMID- 29573050
TI  - MRI for solitary pulmonary nodule and mass assessment: Current state of the art.
AB  - : Since the clinical introduction of magnetic resonance imaging (MRI), the chest
      has been one of its most challenging applications, and many physicists and
      radiologists have tried since the 1980s to use MR for assessment of different
      lung diseases as well as mediastinal and pleural diseases. Since then, however,
      technical advances in sequencing, scanners, and coils, adaptation of parallel
      imaging techniques, utilization of contrast media, and development of
      postprocessing tools have been reported by many basic and clinical researchers.
      As a result, state-of-the-art thoracic MRI is now substituted for traditional
      imaging techniques and/or plays a complementary role in the management of
      patients with various chest diseases, and especially in the detection of
      pulmonary nodules and in thoracic oncology. In addition, MRI has continued to be
      developed to help overcome the limitations of computed tomography (CT) and
      nuclear medicine examinations. It can currently provide not only morphological,
      but also functional, physiological, pathophysiological, and molecular information
      at 1.5T with a gradual shift from 1.5T to 3T MR systems. In this review, we focus
      on these recent advances in MRI for pulmonary nodule detection and pulmonary
      nodule and mass evaluation by using noncontrast-enhanced and contrast-enhanced
      techniques as well as new molecular imaging methods such as chemical exchange
      saturation transfer imaging for a comparison with other modalities such as single
      or multidetector row CT, 18F-fluoro-2-deoxyglucose positron emission tomography
      (FDG-PET), and/or PET/CT. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J.
      Magn. Reson. Imaging 2018;47:1437-1458.

PMID- 29573051
TI  - Altered attentional control linked to catastrophizing in patients with irritable
      bowel syndrome.
AB  - OBJECTIVES: Our study aimed to investigate differences in attentional control
      between patients with irritable bowel syndrome (IBS) and healthy participants and
      to examine the link between attentional control and IBS catastrophizing. Previous
      research has shown that patients with chronic functional illnesses have lower
      levels of attentional control. However, no previous study has found altered
      attentional control in patients with IBS or directly investigated the link
      between attentional control and catastrophizing. We also aimed to establish
      whether anxiety is associated with attentional functions in patients with IBS.
      DESIGN AND METHODS: In this cross-sectional study, we compared 41 IBS patients
      with 39 healthy-matched control participants on attentional functions using an
      attention network task. IBS catastrophizing (Gastrointestinal Cognitions), IBS
      symptom severity (GSRS-IBS), Depression, Anxiety, and Stress (DASS-21), and
      Visceral Anxiety Sensitivity were assessed using self-report measures. RESULTS:
      Patients with IBS had lower attentional control compared to healthy participants,
      t (78) = -2.75, p = .007, d = .62. Groups did not differ in alerting or orienting
      attention. IBS patients with lower attentional control scored higher on IBS
      catastrophizing than those with higher attention control, t (38.59) = 2.19, p =
      .032, d = .66. Anxiety was related to orienting attention in the IBS group (rho =
      .38, p = .015). CONCLUSIONS: Patients with IBS displayed reduced attentional
      control. Crucially, those patients with lower attentional control also had more
      catastrophizing thoughts than patients with better attentional control. These
      findings suggest that improving attentional control could be a valid target for
      psychological interventions for IBS. Statement of contribution What is already
      known on this subject? It has been hypothesised that psychological processes play
      a role in the maintenance of irritable bowel syndrome (IBS), and altered levels
      of attentional control have been found in patients with other functional
      illnesses but not yet in patients with IBS. Pain catastrophizing, a maladaptive
      thinking pattern, has been linked with IBS symptom severity, and previous
      research has shown an association between attentional control and intrusive
      thoughts. Whether there is an association between catastrophizing thoughts and
      attentional control in patients with IBS is unknown. What does this study add?
      Patients with irritable bowel syndrome show reduced levels of attentional
      control. IBS patients with lower levels of attentional control have more
      catastrophizing thoughts. Therapies emphasizing attentional control training may
      help reduce catastrophizing.

PMID- 29573052
TI  - A homozygous variant disrupting the PIGH start-codon is associated with
      developmental delay, epilepsy, and microcephaly.
AB  - Defective glycosylphosphatidylinositol (GPI)-anchor biogenesis can cause a
      spectrum of predominantly neurological problems. For eight genes critical to this
      biological process, disease associations are not yet reported. Scanning exomes
      from 7,833 parent-child trios and 1,792 singletons from the DDD study for
      biallelic variants in this gene-set uncovered a rare PIGH variant in a boy with
      epilepsy, microcephaly, and behavioral difficulties. Although only 2/2 reads
      harbored this c.1A > T transversion, the presence of ~25 Mb autozygosity at this
      locus implied homozygosity, which was confirmed using Sanger sequencing. A
      similarly-affected sister was also homozygous. FACS analysis of PIGH-deficient
      CHO cells indicated that cDNAs with c.1A > T could not efficiently restore
      expression of GPI-APs. Truncation of PIGH protein was consistent with the
      utilization of an in-frame start-site at codon 63. In summary, we describe
      siblings harboring a homozygous c.1A > T variant resulting in defective GPI
      anchor biogenesis and highlight the importance of exploring low-coverage variants
      within autozygous regions.

PMID- 29573053
TI  - Barriers to and enablers of implementing antimicrobial stewardship programs in
      veterinary practices.
AB  - BACKGROUND: Antimicrobial stewardship (AMS) programs are yet to be widely
      implemented in veterinary practice and medical programs are unlikely to be
      directly applicable to veterinary settings. OBJECTIVE: To gain an in-depth
      understanding of the factors that influence effective AMS in veterinary practices
      in Australia. METHODS: A concurrent explanatory mixed methods design was used.
      The quantitative phase of the study consisted of an online questionnaire to
      assess veterinarians' attitudes to antimicrobial resistance (AMR) and
      antimicrobial use in animals, and the extent to which AMS currently is
      implemented (knowingly or unknowingly). The qualitative phase used semi
      structured interviews to gain an understanding of the barriers to and enablers of
      AMS in veterinary practices. Data were collected and entered into NVivo v.11,
      openly coded and analyzed according to mixed methods data analysis principles.
      RESULTS: Companion animal, equine, and bovine veterinarians participated in the
      study. Veterinary practices rarely had antimicrobial prescribing policies. The
      key barriers were a lack of AMS governance structures, client expectations and
      competition between practices, cost of microbiological testing, and lack of
      access to education, training and AMS resources. The enablers were concern for
      the role of veterinary antimicrobial use in development of AMR in humans, a sense
      of pride in the service provided, and preparedness to change prescribing
      practices. CONCLUSION AND CLINICAL IMPORTANCE: Our study can guide development
      and establishment of AMS programs in veterinary practices by defining the major
      issues that influence the prescribing behavior of veterinarians.

PMID- 29573054
TI  - Relational ethics of delirium care: Findings from a hospice ethnography.
AB  - Delirium, a common syndrome in terminally ill people, presents specific
      challenges to a good death in end-of-life care. This paper examines the
      relational engagement between hospice nurses and their patients in a context of
      end-of-life delirium. Ethnographic fieldwork spanning 15 months was conducted at
      a freestanding residential hospice in eastern Canada. A shared value system was
      apparent within the nursing community of hospice; patients' comfort and dignity
      were deemed most at stake and therefore commanded nurses' primary attention. This
      overarching commitment to comfort and dignity shaped all of nursing practice in
      this hospice, including practices related to end-of-life delirium. The findings
      of this study elaborate the ways in which hospice nurses interpreted and
      responded to the discomfort of their patients in delirium, as well as the efforts
      they made to understand their patients' subjective experiences and to connect
      with them in supportive ways. In addition to what is already known about clinical
      assessment and treatment of delirium in palliative care settings, the findings of
      this study offer points of reflection for nurses anywhere who are contending with
      the relational challenges that delirium presents in end-of-life care.

PMID- 29573056
TI  - Physicians, sick leave certificates, and patients' subsequent employment
      outcomes.
AB  - I analyze how general practitioners (GPs) indirectly affect their patients'
      employment outcomes by deciding the length of sick leaves. I use an instrumental
      variables framework where spell durations are identified through supply-side
      certification measures. I find that a day of sick leave certified only because
      the worker's GP has a high propensity to certify sick leaves decreases the
      employment probability persistently by 0.45-0.69 percentage points, but increases
      the risk of becoming unemployed by 0.28-0.44 percentage points. These effects are
      mostly driven by workers with low job tenure. Several robustness checks show that
      endogenous matching between patients and GPs does not impair identification. My
      results bear important implications for doctors: Whenever medically justifiable,
      certifying shorter sick leaves to protect the employment status of the patient
      may be beneficial.

PMID- 29573055
TI  - Effect of cross-match on packed cell volume after transfusion of packed red blood
      cells in transfusion-naive anemic cats.
AB  - BACKGROUND: Novel feline RBC antigens might contribute to decreased efficacy of
      RBC transfusion and increased incidence of acute transfusion reactions (ATR).
      OBJECTIVES: To examine the effect of major cross-match in transfusion-naive
      anemic cats on the incidence of acute immunologic transfusion reaction and
      transfusion efficacy for up to 24 hours after transfusion. ANIMALS: Forty-eight
      client owned transfusion-naive anemic cats. METHODS: Prospective, randomized,
      controlled study. All transfusion-naive cats receiving packed red blood cells
      (pRBC) transfusions from January 2016 to August 2017 were eligible for inclusion.
      Cats in the study group received cross-match and blood type compatible pRBCs and
      cats in the control group received noncross-matched blood type compatible pRBCs.
      Incidence of ATR and change in PCV after transfusion was recorded. RESULTS: No
      significant difference in incidence of transfusion reactions between cross
      matched and noncross-matched groups (CM+ 4/24; 17%, CM- 7/24; 29%, P = .16). No
      significant difference between groups in mean change in PCV after transfusion
      scaled to dose of pRBCs administered at any time point after transfusion
      (immediate: CM+ 0.62 +/- 0.59, CM- 0.75 +/- 0.48, P = .41; 1 hour: CM+ 0.60 +/-
      0.66, CM- 0.74 +/- 0.53, P = .43; 12 hours: CM+ 0.70 +/- 0.55, CM- 0.66 +/- 0.60,
      P = .81; 24 hours: CM+ 0.64 +/- 0.71, CM- 0.55 +/- 0.48, P = .70). CONCLUSIONS
      AND CLINICAL IMPORTANCE: Our results do not support use of the major cross-match
      test to increase efficacy of, and to decrease adverse events associated with, RBC
      transfusion in AB blood typed transfusion-naive cats.

PMID- 29573057
TI  - Diagnosis of citrullinemia type 1 carriage after identification of mild
      citrullinemia on neonatal screening.

PMID- 29573058
TI  - Molecular genomic landscapes of hepatobiliary cancer.
AB  - Hepatocellular carcinoma (HCC) and biliary tract cancer are more frequent in East
      Asia including Japan than in Europe or North America. A compilation of 1340 multi
      ethnic HCC genomes, the largest cohort ever reported, identified a comprehensive
      landscape of HCC driver genes, comprised of three core drivers (TP53, TERT, and
      WNT signaling) and combinations of infrequent alterations in various cancer
      pathways. In contrast, five core driver genes (TP53, ARID1A, KRAS, SMAD4, and
      BAP1) with characteristic molecular alterations including fusion transcripts
      involving fibroblast growth factor receptor 2 and the protein kinase A pathway,
      and IDH1/2 mutation constituted the biliary tract cancer genomes. Consistent with
      their heterogeneous epidemiological backgrounds, mutational signatures and
      combinations of non-core driver genes within these cancer genomes were found to
      be complex. Integrative analyses of multi-omics data identified molecular
      classifications of these tumors that are associated with clinical outcome and
      enrichments of potential therapeutic targets, including immune checkpoint
      molecules. Translating comprehensive molecular-genomic analysis together with
      further basic research and international collaborations are highly anticipated
      for developing precise and better treatments, diagnosis, and prevention of these
      tumor types.

PMID- 29573059
TI  - Community managed alcohol programs in Canada: Overview of key dimensions and
      implementation.
AB  - INTRODUCTION AND AIMS: People with severe alcohol dependence and unstable housing
      are vulnerable to multiple harms related to drinking and homelessness. Managed
      Alcohol Programs (MAP) aim to reduce harms of severe alcohol use without
      expecting cessation of use. There is promising evidence that MAPs reduce acute
      and social harms associated with alcohol dependence. The aim of this paper is to
      describe MAPs in Canada including key dimensions and implementation issues.
      DESIGN AND METHODS: Thirteen Canadian MAPs were identified through the Canadian
      Managed Alcohol Program Study. Nine key informant interviews were conducted and
      analysed alongside program documents and reports to create individual case
      reports. Inductive content analysis and cross case comparisons were employed to
      identify six key dimensions of MAPs. RESULTS: Community based MAPs have a common
      goal of preserving dignity and reducing harms of drinking while increasing access
      to housing, health and social services. MAPs are offered as both residential and
      day programs with differences in six key dimensions including program goals and
      eligibility, food and accomodation, alcohol dispensing and administration,
      funding and money management, primary care services and clinical monitoring, and
      social and cultural connections. DISCUSSION AND CONCLUSIONS: MAPs consist of four
      pillars with the alcohol intervention provided alongside housing interventions,
      primary care services, social and cultural interventions. Availability of
      permanent housing and re-establishing social and cultural connections are central
      to recovery and healing goals of MAPs. Additional research regarding Indigenous
      and gendered approaches to program development as well as outcomes related to
      chronic harms and differences in alcohol management are needed.

PMID- 29573060
TI  - An alternative approach to the current diagnostic guidelines for fibrotic
      interstitial lung disease.

PMID- 29573062
TI  - Developing Student Evidence-Based Practice Questionnaire (S-EBPQ) for
      undergraduate nursing students: Reliability and validity of a Chinese adaptation.
AB  - RATIONALE, AIMS, AND OBJECTIVES: The assessment of evaluating undergraduate
      nursing students' evidence-based practice engagement is an important issue, yet
      few tools have been developed specifically in Mainland China. The purpose of this
      study was to adapt the Student Evidence-based Practice Questionnaire (S-EBPQ) to
      Mainland China's cultural context and to evaluate the psychometric properties of
      the newly adapted Chinese S-EBPQ. METHODS: Cross-cultural adaptation, including
      translation of the original S-EBPQ into Mandarin Chinese language, was performed
      according to published guidelines. A pilot study was conducted in Mainland China
      with 25 Chinese undergraduate nursing students. A subsequent validation study was
      conducted with 400 undergraduate nursing students from Mainland China. Construct
      validity was assessed by exploratory factor analysis (n = 190) and confirmatory
      factor analysis (n = 210). Reliability was determined using internal consistency
      and test-retest reliability. RESULTS: The split-half coefficient for the overall
      Chinese S-EBPQ was 0.858. A content validity index of 0.986 was achieved.
      Principal component analysis resulted in a 4-factor structure explaining 68.285%
      of the total variance. The comparative fit index was 0.927, and the root mean
      squared error of approximation was 0.072 from the confirmatory factor analysis.
      Known-group validity was supported by the significant differences according to
      various characteristics of participants. Internal consistency was high for the
      Chinese S-EBPQ reaching a Cronbach alpha value of 0.934. Test-retest reliability
      was 0.821. CONCLUSION: The newly cross-culturally adapted S-EBPQ possesses
      adequate validity, test-retest reliability, and internal consistency and
      therefore may be utilized in nursing education to assess EBP of undergraduate
      nursing students in Mainland China.

PMID- 29573061
TI  - Circulating exosomes contain protein biomarkers of metastatic non-small-cell lung
      cancer.
AB  - The present study aimed to investigate the overall changes in exosomal proteomes
      in metastatic and non-metastatic non-small-cell lung cancers (NSCLC) and healthy
      human serum samples, and evaluate the potential of serum exosomal biomarkers to
      predict NSCLC metastasis. Tandem mass tags combined with multidimensional liquid
      chromatography and mass spectrometry analysis were used for screening the
      proteomic profiles of serum samples. Quantitative proteome, significant pathway,
      and functional categories of patients with metastatic and non-metastatic NSCLC
      and healthy donors were investigated. In total, 552 proteins of the 628 protein
      groups identified were quantified. Bioinformatics analysis indicated that
      quantifiable proteins were mainly involved in multiple biological functions,
      metastasis-related pathways. Moreover, lipopolysaccharide-binding proteins (LBP)
      in the exosomes were found to be well distinguished between patients with
      metastatic and patients with non-metastatic NSCLC. Area under the curve (AUC) was
      0.803 with a sensitivity of 83.1% and a specificity of 67% (P < .0001).
      Circulating LBP were also well distinguishable between metastatic and non
      metastatic NSCLC, the AUC was 0.683 with a sensitivity of 79.5% and a specificity
      of 47.2% (P = .005). This novel study provided a reference proteome map for
      metastatic NSCLC. Patients with metastatic and non-metastatic NSCLC differed in
      exosome-related proteins in the serum. LBP might be promising and effective
      candidates of metastatic NSCLC.

PMID- 29573063
TI  - Pattern of video game use in children with attention-deficit-hyperactivity
      disorder and typical development.
AB  - BACKGROUND: Video game playing is a favorite leisure activity among children
      worldwide. Individuals with attention-deficit-hyperactivity disorder (ADHD) often
      lack self-control, making them at risk for substance abuse and game addiction.
      There are conflicting results, however, between studies on the pattern of video
      gaming and game addiction between those with ADHD and healthy controls. We
      therefore compared the pattern of video game use and game addiction between Thai
      children with ADHD and healthy controls. METHODS: A total of 80 participants with
      ADHD (median age, 9.5 years) and 102 controls (median age, 10 years) were
      recruited in this study. ADHD was diagnosed by a developmental pediatrician. Each
      control subject's teacher completed the ADHD questionnaire to ensure that they
      did not have the diagnosis of ADHD. Pattern of video game use and Game Addiction
      Screening Test (GAST) were completed by participants' parents. RESULTS: More than
      half of the children with and without ADHD spent >2 h/day playing video games
      rather than engaging in other age-appropriate leisure activities, particularly on
      weekends. Participants with ADHD, however, had a higher rate of compulsive video
      game use than controls (37.5% vs 11.8%, P < 0.001). CONCLUSIONS: Although video
      game playing was relatively prevalent in children regardless of ADHD status,
      those with ADHD had a higher rate of problematic video game use than controls.
      The pattern of leisure activities including video game use should be assessed
      during health supervision visits. As such, those at risk for game addiction could
      be identified early, resulting in appropriate intervention.

PMID- 29573064
TI  - Prevalence, risk factors and complications of oropharyngeal dysphagia in stroke
      patients: A cohort study.
AB  - BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent poststroke condition with
      severe complications and increased mortality. Poststroke OD prevalence varies
      among studies and there is little evidence of its related risk factors and
      associated complications. OBJECTIVE: to evaluate the prevalence of OD after
      stroke and the risk factors and associated complications. METHODS: We performed a
      prospective longitudinal study of stroke patients consecutively admitted to a
      general hospital. OD was diagnosed with the volume-viscosity swallow test (V
      VST). Demographic, functional status and topographical and clinical variables of
      stroke were collected to assess risk factors for OD. We evaluated functional
      status, mortality, respiratory infections, and readmissions 3 and 12 months after
      stroke. A multivariate regression analysis determined associated risk factors for
      OD and for each outcome variable. KEY RESULTS: We included 395 stroke patients
      with a 45.06% prevalence of OD on admission. OD was independently associated with
      age (OR = 1.05; CI = 1.02-1.08), previous stroke (OR = 2.40; CI = 1.00-5.79),
      severity using the National Institute of Health Stroke Scale (OR = 3.52; CI =
      1.57-7.87) and volume of the lesion (OR = 1.02; CI = 1.01-1.03). OD after stroke
      was an independent risk factor for prolonged hospital stay (P = .049; beta =
      0.938) and institutionalization after discharge (OR = 0.47; CI = 0.24-0.92); OD
      was an independent risk factor for poorer functional capacity (OR = 3.00; CI =
      1.58-5.68) and increased mortality (HR = 6.90; CI = 1.57-30.34) 3 months after
      stroke. CONCLUSIONS & INFERENCES: Poststroke OD is prevalent and associated with
      poor short and long term prognosis. Stroke severity and patient status before
      stroke were more relevant to OD than lesion location. Systematic screening
      programs and early OD management could significantly improve poststroke patient
      outcome.

PMID- 29573065
TI  - The prevalence of second canals in the mesiobuccal root of maxillary molars: A
      cone beam computed tomography study.
AB  - The aim of this study was to determine the prevalence of MB2 canals in permanent
      maxillary molars utilising CBCT; in patients attending a university hospital. A
      total of 200 patient scans, (100 female and 100 male patients), were enrolled in
      the study. In total, 800 teeth were analysed, and teeth with additional canals in
      their MB roots (MB2) were identified. First maxillary molar teeth exhibited the
      highest prevalence of MB2 canals, 92% and 87%, for teeth 16 and 26, respectively.
      Second maxillary molar teeth showed a lower prevalence of MB2 canals, 69% and
      65%, for the 17 and 27, respectively. There were no associations of significance
      between the prevalence of MB2 canals and patient age or gender. Root morphology
      and anatomy of permanent maxillary first and second molar teeth was found to be
      highly variable. The prevalence of additional canals in the MB roots is a
      frequent finding which has previously been underreported.

PMID- 29573066
TI  - Infant colic or early symptom of autism spectrum disorder?
AB  - BACKGROUND: Gastrointestinal (GI) disorders are common in autism spectrum
      disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not
      been evaluated in this patient group. The aim of this study was therefore to
      determine the rate of IC in ASD and investigate a possible association between
      ASD and IC. METHODS: The subjects consisted of 100 ASD patients (mean age, 6.6 +/
      3.5 years) and 100 healthy controls (mean age, 5.3 +/- 2.8 years). The parents
      were questioned using the diagnostic criteria for infant colic for clinical
      research purposes defined in Rome IV to diagnose IC, retrospectively. The sample
      size was estimated using a maximum type I error probability of 5% (alpha) and a
      type II error of 20%. RESULTS: The rate of IC was 16% and 17% in the ASD group
      and control group, respectively (P ? 0.05). Excessive crying with late onset and
      long duration in infants was defined as persistent crying. The rate of persistent
      crying was significantly higher in the ASD group than in the control group (32%
      vs 9%, P < 0.001). The relative risk of persistent crying was 4.40 in ASD. The
      likelihood of being misdiagnosed with IC in this group was 78%. CONCLUSION: The
      rate of IC is not increased in patients with ASD, but infants with excessive
      crying should be very thoroughly evaluated before being diagnosed with IC. In
      particular, persistent crying in infants (i.e. excessive crying with late onset
      and long duration) may be an early symptom of ASD.

PMID- 29573067
TI  - Single-use flexible bronchoscopes compared with reusable bronchoscopes: Positive
      organizational impact but a costly solution.
AB  - RATIONALE, AIMS, AND OBJECTIVES: There is at present no standard methodology to
      analyse the organizational impacts (OIs) of medical devices (MDs), and the field
      is still in its infancy. The aim of the present study was to assess, at a
      hospital level, the organizational and economic impacts of the introduction of a
      new MD, specifically the single-use flexible bronchoscope (FB). METHODS: Both the
      organizational and economic impacts of the single-use FB were evaluated in
      comparison with the reusable FB currently used as standard practice in our
      institution. First, process maps were created for both devices (reusable and
      single use). Based on the 12 types of OI defined by Roussel et al, interviews
      were conducted with all stakeholders, and the positive and negative aspects of
      the reusable and single-use processes were analysed. In a second step,
      microcosting analysis was conducted to determine the most economical balance in
      use of the 2 technologies. RESULTS: Process maps highlighted the complexity of
      the reusable device process when compared with the single-use device process.
      Among the 12 types of OI, the single-use FB process scored better than the
      reusable FB process in 75% of cases. With the "fleet" of 15 reusable FBs
      available in our institution, using single-use FBs would represent an extra cost
      of ?154 per procedure. Single-use and reusable devices would have the same cost
      (?232 per procedure) with a theoretical annual activity of 328 bronchoscopies,
      which is much lower than our current activity (1644 procedures per year).
      CONCLUSIONS: Organizational impact should be considered when assessing MDs. We
      show in this study that from an organizational viewpoint, there are many
      advantages to using single-use bronchoscopes. However, in economic impact, it is
      more cost-effective for our institution, with more than 1500 bronchoscopies
      performed annually, to use reusable devices.

PMID- 29573068
TI  - Revealing the Formation Mechanism of CsPbBr3 Perovskite Nanocrystals Produced via
      a Slowed-Down Microwave-Assisted Synthesis.
AB  - We developed a microwave-assisted slowed-down synthesis of CsPbBr3 perovskite
      nanocrystals, which retards the reaction and allows us to gather useful insights
      into the formation mechanism of these nanoparticles, by examining the
      intermediate stages of their growth. The trends in the decay of the emission
      intensity of CsPbBr3 nanocrystals under light exposure are well correlated with
      their stability against decomposition in TEM under electron beam. The results
      show the change of the crystal structure of CsPbBr3 nanocrystals from a deficient
      and easier to be destroyed lattice to a well crystallized one. Conversely the
      shift in the ease of degradation sheds light on the formation mechanism,
      indicating first the formation of a bromoplumbate ionic scaffold, with Cs-ion
      infilling lagging a little behind. Increasing the cation to halide ratio towards
      the stoichiometric level may account for the improved radiative recombination
      rates observed in the longer reaction time materials.

PMID- 29573069
TI  - Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal
      integrity in a murine model of nonerosive reflux disease.
AB  - BACKGROUND: Microscopic inflammation and impairment of the esophageal epithelial
      barrier are considered relevant for perception of symptoms in patients with
      nonerosive reflux disease (NERD). In these patients, the receptor transient
      receptor potential vanilloid 1 (TRPV1) is overexpressed in the esophageal mucosa,
      but its role is not yet fully understood. We evaluated the role of TRPV1 in
      esophageal inflammation and mucosal barrier impairment in a murine model of NERD.
      METHODS: Nonerosive reflux disease was surgically induced in Swiss mice by
      pyloric substenosis and ligature of the gastric fundus, and the mice were killed
      7 days post surgery. The experimental groups were: I, sham surgery (negative
      control); II, NERD untreated; III and IV, NERD + SB366791 or capsazepine (TRPV1
      antagonists); and V, NERD + resiniferatoxin (for long-term desensitization of
      TRPV1). The esophagus was collected for western blotting and histopathology and
      for evaluation of wet weight, myeloperoxidase (MPO), keratinocyte-derived
      chemokine (KC), transepithelial electrical resistance (TEER), and basal
      permeability to fluorescein. KEY RESULTS: Compared to sham, NERD mice had
      increased esophageal wet weight and MPO and KC levels. The mucosa had no ulcers
      but exhibited inflammation. NERD mice showed mucosal TRPV1 overexpression, a more
      pronounced decrease in TEER at pH 0.5 (containing pepsin and taurodeoxycholic
      acid), and increased basal permeability. Pharmacological modulation of TRPV1
      prevented esophageal inflammation development, TEER changes by acidic exposure,
      and increase in esophageal permeability. CONCLUSIONS & INFERENCES: The TRPV1
      receptor has a critical role in esophageal inflammation and mucosal barrier
      impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target
      in patients with NERD.

PMID- 29573070
TI  - Geriatric Psychotropic Stewardship Team to de-escalate inappropriate psychotropic
      medications in general medicine inpatients: An evaluation.
AB  - OBJECTIVES: To assess the feasibility and effectiveness of a Geriatric
      Psychotropic Stewardship Team (GPST) and to achieve inpatient de-escalation of
      inappropriate psychotropic medications in patients aged over 65 years on a
      general medicine ward. METHODS: A multidisciplinary GPST conducted twice-weekly
      rounds on general medicine inpatients known to be taking psychotropic
      medications. A consensus recommendation was generated, with subsequent treating
      team action recorded. RESULTS: A total of 125 patients taking 180 psychotropic
      medications were identified for GPST review. Of these, 32 medications (18%) had
      been ceased by the treating team prior to GPST review. Adoption of GPST
      recommendations at 24 hours and at discharge occurred for 85 medications (57%)
      and 79 medications (53%), respectively. CONCLUSIONS: This study demonstrates the
      feasibility of a structured multidisciplinary approach in the de-escalation of
      inappropriate psychotropic medications in older hospital patients on a general
      medicine ward. Further studies are required to assess scalability and long-term
      clinical outcomes.

PMID- 29573071
TI  - Endodontic decision making for asymptomatic root-filled teeth with apical
      periodontitis - A radiographic survey.
AB  - The aim of the study was to compare decision making for asymptomatic root-filled
      teeth among dentists with differing educational backgrounds. Case scenarios based
      on 14 radiographs were created and 150 participants were asked to choose from
      five alternative treatment decisions and to state the rationale. Demographic data
      of the participants were recorded. Frequency distribution and cross-tabulation
      were performed; chi square testing was used for comparisons and logistic
      regression was performed to detect significant differences. The overall response
      rate was 87.3%. The practitioners chose intervention predominantly with non
      surgical retreatment a common choice. Poor technical quality was a driving
      factor, while the existing poor coronal restoration and the need for a crown were
      generally not taken into account by general dentists. Speciality and experience
      were significant factors. Practitioners were more inclined to retain rather than
      extract teeth. It is concluded that clear guidelines listing factors to consider
      for intervention are required.

PMID- 29573072
TI  - Prevalence and risk factors of halitosis in Japanese school children.
AB  - BACKGROUND: Little data are available regarding halitosis in Japanese children.
      The aim of the current study was to investigate the prevalence and risk factors
      associated with halitosis in Japanese elementary and junior high school children.
      METHODS: The subjects consisted of 520 elementary (1st-6th grade: boys, n = 284;
      girls, n = 236) and 248 junior high (7th-9th grade: boys, n = 136; girls, n =
      112) school children aged 6-15 years in Saitama Prefecture, Japan. A self
      administered questionnaire survey; halitosis measurement using an organoleptic
      assessment method; and clinical oral examination were conducted. RESULTS:
      Overall, 44.9% of subjects had halitosis. The proportion of boys with halitosis
      was 43.6% and that of girls was 46.6%. On logistic regression analysis, grade and
      tongue coating were significant predictors of halitosis. The 7th-9th graders were
      significantly more likely to have halitosis than 1st-3rd graders (OR, 1.83; P =
      0.007). Subjects with area of tongue coating score 2 or 3 were 5.51-fold more
      likely to present with halitosis (P < 0.001) than those with area of tongue
      coating score 0 or 1. Similarly, subjects with thickness of tongue coating score
      2 or 3 were 3.28-fold more likely to have halitosis than those with thickness of
      tongue coating score 0 or 1 (P < 0.001). CONCLUSIONS: Halitosis in the school
      children is not a rare condition; instead, its occurrence is relatively high.
      Therefore, inclusion of a halitosis prevention and management component in school
      oral health programs would lead to the promotion of overall oral health.

PMID- 29573073
TI  - Reconfigurable DNA Nanoswitches for Graphical Readout of Molecular Signals.
AB  - This study reports a DNA nanoswitch that can be used for visual display of
      outputs resulting from hybridization events of specific molecular inputs.
      Conformational changes of the DNA nanoswitch triggered by input DNA strands yield
      different "pixels" that collectively produce a graphical output on an agarose
      gel. This system has potential in molecular computation and biosensing approaches
      in which individual binding results can be translated into macromolecular visual
      readouts.

PMID- 29573074
TI  - Under-utilisation of beta-blockers in patients with acute coronary syndrome and
      comorbid chronic obstructive pulmonary disease.
AB  - BACKGROUND: beta-blockers are an established mainstay of therapy in acute
      coronary syndrome (ACS). Despite substantial evidence of their safety and
      efficacy in chronic obstructive pulmonary disease (COPD) patients, their use in
      this population remains limited internationally, likely due to fears of inducing
      bronchospasm. In Australia, little is known about the use of beta-blockers in
      COPD patients hospitalised for ACS. AIM: To determine if beta-blockers are under
      prescribed at discharge for patients with COPD hospitalised for ACS compared to
      patients without a diagnosis of COPD. METHODS: Retrospective analysis of a
      tertiary metropolitan hospital computer database was undertaken to identify the
      first 250 patients hospitalised with ACS from 1 March 2015. RESULTS: Of the 250
      patients analysed, there were five in-hospital fatalities, leaving 245 patients
      for final analysis. Patients with ACS and COPD received fewer beta-blockers at
      discharge than those with ACS alone (66.7% vs 86.2%, P < 0.05). After controlling
      for clinically meaningful confounding factors, a logistic regression analysis
      model determined that, for patients with ACS, the presence of COPD was the only
      significant predictor of receiving a beta-blocker at discharge. CONCLUSION:
      Despite strong evidence supporting the use of beta-blockers in COPD patients with
      ACS, Australian patients with COPD remain under-treated for ACS. More work is
      needed to alter prescribing attitudes.

PMID- 29573075
TI  - Plasmodium falciparum infection transmitted by transfusion: A cause of
      hemophagocytic syndrome after bone marrow tranplantation in a non-endemic
      country.
AB  - A 27-year-old man with severe aplastic anemia underwent bone marrow
      transplantation from his HLA identical brother in July 2016. Conditioning
      included ATGAM 30 mg/kg for 3 days and Cyclophosphamide 50 mg/kg for 4 days. The
      patient received several platelet and red blood cell transfusions before and
      after the conditioning. The patient received broad spectrum antibiotics and
      caspofungin because persistant febrile neutropenia without bacteriological or
      mycological documentation. Hemophagocytic syndrome was diagnosed on day +12.
      Steroids at 1 mg/kg were started on day +12. Fever resolved the same day but
      resumed 3 days later associated to intravascular hemolysis with no schizocytes on
      blood smears and negative DAT. Thick blood film smears performed on day +26
      revealed Plasmodium falciparum parasites (parasitemia = 20%). Except the level of
      parasitemia, there were no signs of gravity. Quinine was started on day 26 at a
      loading dose of 15 mg/kg followed by 8 mg/kg three times a day for 20 doses.
      Fever vanished after 2 days. Parasitemia cleared in 3 days and remained negative
      thereafter. Investigations revealed that the patient was transfused by a red cell
      unit harvested in a voluntary donor native of a malaria endemic country. PCR for
      P. falciparum performed in this donor in the frame of investigations was
      positive. The patient is alive with a normal blood count 1 year after BMT.

PMID- 29573077
TI  - Electronic Communication between two [10]cycloparaphenylenes and
      Bis(azafullerene) (C59 N)2 Induced by Cooperative Complexation.
AB  - The complex of [10]cycloparaphenylene ([10]CPP) with bis(azafullerene) (C59 N)2
      is investigated experimentally and computationally. Two [10]CPP rings are bound
      to the dimeric azafullerene giving [10]CPP?(C59 N)2 ?[10]CPP. Photophysical and
      redox properties support an electronic interaction between the components
      especially when the second [10]CPP is bound. Unlike [10]CPP?C60 , in which there
      is negligible electronic communication between the two species, upon
      photoexcitation a partial charge transfer phenomenon is revealed between [10]CPP
      and (C59 N)2 reminiscent of CPP-encapsulated metallofullerenes. Such an
      alternative electron-rich fullerene species demonstrates C60 -like ground-state
      properties and metallofullerene-like excited-state properties opening new avenues
      for construction of functional supramolecular architectures with organic
      materials.

PMID- 29573078
TI  - Characteristics of fall-related traumatic brain injury in older adults.
AB  - BACKGROUND: Older adults admitted for falls and its complications, including
      traumatic brain injury (TBI), is increasing. Recent studies have shown that those
      with falls who presented to the emergency department (ED) had an increased
      frequency of ED revisits, especially those with head trauma. AIM: To determine
      the characteristics and predictors of fall-related traumatic brain injury (FRTBI)
      in older adults. METHODS: Retrospective medical chart review of 339 patients aged
      65 years and older admitted for TBI in 2014 due to a fall. Characteristics
      analysed include demographics, fall circumstances, prior ED visits, polypharmacy,
      readmission, functional status and specialist outpatient clinic utilisation
      before and after FRTBI. RESULTS: A total of 339 (37.4%) patients admitted due to
      FRTBI was 65 years old and older; 112 (33.0%) for subdural haemorrhage (SDH); 227
      (67.0%) for head injury (HI), with a mean age of 80 years. A total of 46 (41.1%)
      patients with SDH and 107 (47.1%) with HI had a previous ED visit within the last
      year, while 22 (19.6%) of SDH and 49 (21.6%) of HI had hospitalisation 3 months
      prior to FRTBI. FRTBI was associated with significant decline in activities of
      daily living, polypharmacy and increased specialist outpatient clinic
      appointments (P < 0.001). Mortality was 11 (3.2%). Mild cognitive impairment or
      dementia was significantly associated with admissions for FRTBI, 3.31 (95%
      confidence interval 1.68-6.51, P = 0.001) using adjusted logistic regression.
      CONCLUSION: FRTBI is associated with significant functional decline and increased
      resource utilisation with almost half of the patients having had prior ED visits
      or hospitalisation. Future studies should focus on falls risk assessment and
      interventions for high-risk older adults prior to discharge from ED and hospital,
      and its impact on readmissions due to FRTBI.

PMID- 29573079
TI  - Improving the quality of life of aged care residents through the joy of food: The
      Lantern Project.
AB  - OBJECTIVE: Mealtimes directly impact the quality of life of residents in aged
      care. The objective of The Lantern Project is to improve the dining experience of
      aged care residents to reduce malnutrition risk through improving dietary intake,
      meal. METHODS: A transdisciplinary team of aged care professionals and resident
      advocates was formed as a collaboration collectively known as The Lantern
      Project. RESULTS: This paper outlines the journey and timeline of The Lantern
      Project collaboration since its inception and the interplay between the monthly
      stakeholder meetings and inter-related research projects demonstrating improved
      outcomes. CONCLUSION: Transdisciplinary collaboration offers well-grounded
      benefits and realistic strategies sensitive to the complexity of the aged care
      setting.

PMID- 29573076
TI  - Biocatalytic Oxidation Reactions: A Chemist's Perspective.
AB  - Oxidation chemistry using enzymes is approaching maturity and practical
      applicability in organic synthesis. Oxidoreductases (enzymes catalysing redox
      reactions) enable chemists to perform highly selective and efficient
      transformations ranging from simple alcohol oxidations to stereoselective
      halogenations of non-activated C-H bonds. For many of these reactions, no
      "classical" chemical counterpart is known. Hence oxidoreductases open up shorter
      synthesis routes based on a more direct access to the target products. The
      generally very mild reaction conditions may also reduce the environmental impact
      of biocatalytic reactions compared to classical counterparts. In this Review, we
      critically summarise the most important recent developments in the field of
      biocatalytic oxidation chemistry and identify the most pressing bottlenecks as
      well as promising solutions.

PMID- 29573080
TI  - Functional dimorphic enantiostyly in monomorphic enantiostylous species of the
      subtribe Cassiinae (Fabaceae-Caesalpinioideae).
AB  - Monomorphic enantiostylous species produce flowers with a displacement of the
      style to the left (L) or right (R) on the same individual, and may exhibit
      different dynamics for the production of these floral types, which may influence
      levels of selfing. We investigated the production dynamics of L and R floral
      types in seven species and a variety of monomorphic enantiostylous species of the
      genera Senna and Chamaecrista. Our hypothesis was that most species present
      similar proportions of floral morphs each day. Individuals were classified daily
      over a period of 7 days according to the functional status, i.e. the proportion
      of floral morphs as functionally L, R or reciprocal (REC, i.e. similar
      proportions of the two floral morphs), and also according to the number of
      consecutive days in which they exhibited the same functional status. All species
      presented low daily flower production. Most species had individuals classified as
      functionally R, L and REC, and tend to repeat the same functional status over a
      few days, although they may change functional status during the flowering period.
      All species exhibited individuals that were classified as functionally reciprocal
      when both the daily and total number of flowers produced over 7 days was
      considered. The occurrence of different functional status has not yet been
      reported in the literature for enantiostylous species. The distinct strategies
      observed in the dynamics of floral morph production seemed likely to minimise
      geitonogamy and to favour cross-pollination between individuals (xenogamy).

PMID- 29573081
TI  - Effect of subconjunctival Bevacizumab injection on the outcome of Ahmed glaucoma
      valve implantation: a randomized control trial.
AB  - IMPORTANCE: The effect of subconjunctival Bevacizumab injection on the outcome of
      Ahmed glaucoma valve (AGV) implantation. BACKGROUND: Evaluation of efficacy and
      safety of subconjunctival Bevacizumab injection adjunctive to AGV implantation.
      DESIGN: Prospective and randomized clinical trial. PARTICIPANTS: Fifty eyes of 50
      patients with diagnosis of glaucoma that were candidate for AGV surgery were
      included. METHODS: In 25 eyes, conventional AGV surgery (group 1) and in 25 eyes
      AGV surgery with subconjunctival Bevacizumab (group 2) was performed by block
      randomization MAIN OUTCOME MEASURES: The primary outcome measure was surgical
      success. Outcome measures were compared at postoperative month 3, 6 and 12.
      RESULTS: Mean age of patients was 58.76 +/- 12.11 and 51.36 +/- 15.44 years in
      group 1 and 2 respectively (P = 0.06). Mean intraocular pressure (IOP) at
      baseline was 24.88 +/- 7.62 mmHg in group 1 and 27.52 +/- 8.57 mmHg in group 2
      which decreased to15.4 +/- 4.4 mmHg in group 1 and 13.42 +/- 2.9 mmHg in group 2
      (P < 0.00) at last follow up. Surgical success was defined in two level:
      postoperative IOP <= 21 mmHg with at least 20% reduction in IOP (Criterion A),
      either with no medication (complete success) or with no more than two medications
      (qualified success) and criterion B with the same definition but the IOP <= 18
      mmHg The cumulative success according to criterion A and B was 77.8%, 72.2% in
      group 1 and 89.5% in group 2, respectively, at the end of follow-up. CONCLUSIONS
      AND RELEVANCE: Subconjunctival injection of Bevacizumab adjunctive to AGV
      implantation leads to higher success rate compared with AGV alone in one year
      follow-up.

PMID- 29573082
TI  - Bilateral posterior capsule injury after Nd:YAG laser vitreolysis: unintended
      consequence of floaters treatment.

PMID- 29573083
TI  - Serum albumin level and abnormal corrected QT interval in patients with coronary
      artery disease and chronic kidney disease.
AB  - BACKGROUND: Lower concentrations of serum albumin appear to be associated with an
      increased risk of all-cause and cardiovascular mortality, coronary heart disease,
      heart failure and stroke. However, little is known about the relationship between
      serum albumin level and prolonged QT interval. AIM: To investigate whether lower
      serum albumin is associated with prolonged QT interval by recording 12-lead
      electrocardiography in patients with coronary artery disease and chronic kidney
      disease. METHODS: This study included 1383 consecutive patients with coronary
      artery disease and chronic kidney disease (841 with acute coronary syndrome and
      542 with elective percutaneous coronary intervention patients) who were enrolled
      in a disease management programme. Twelve-lead electrocardiography was recorded
      in each subject. We assessed the relationship between albumin levels (both as a
      continuous variable and stratified by tertile) at admission and corrected QT
      (QTc) prolongation. RESULTS: Patients with abnormal QTc interval had lower serum
      albumin levels than those with normal and borderline QTc intervals. Statistically
      significant negative associations were observed between serum albumin levels and
      QTc interval (beta = -0.211, P < 0.0001). Using multivariate and trend analyses,
      a lower concentration of serum albumin was independently associated with QTc
      prolongation in both the patients with acute coronary syndrome and elective
      percutaneous coronary intervention patients. CONCLUSION: Concentrations of serum
      albumin were significantly lower in the patients with an abnormal QTc interval
      and were associated with QTc prolongation. Further studies are needed to clarify
      whether lower serum albumin plays a role in the pathogenesis of QTc prolongation.

PMID- 29573084
TI  - The clinician factor: Personality characteristics of clinicians and their impact
      upon clinical outcomes in the management of children and adolescents with type 1
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to estimate clinician qualities that
      influence metabolic outcomes in youth with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Data were gathered over two 3 month periods in a large tertiary diabetes
      center (1500 patients, 8 clinicians) from patients with type 1 diabetes who
      received continuous care from each clinician. Data included sex, age, diabetes
      duration, insulin regimen, body mass index (BMI), insulin dose and episodes of
      severe hypoglycemia. Clinician data included target blood glucose levels, target
      glycated hemoglobin (HbA1c), Diabetes Attitude Scale and Big 5 Personality
      Inventory Scale. Mean HbA1c per clinician was the primary outcome variable.
      RESULTS: The 8 clinicians saw a total of 464 patients during the first time
      period, and 603 in the second time period. Lowest to highest mean HbA1c per
      clinician varied by 0.7%. There were small but statistically significant
      differences between clinicians with their patients' age at diagnosis, duration of
      diabetes, age, gender, treatment type and BMI SD score. After controlling for
      these differences, the clinician characteristics that were associated with lower
      mean HbA1c were having no lower limit in target HbA1c and being self-reportedly
      "less agreeable." The impact of these clinician attitudinal traits was equivalent
      to the combined effects of patient characteristics and treatment type.
      CONCLUSIONS: There was a significant variation in metabolic outcomes between
      treating clinicians. After controlling for patient clinical differences,
      clinician mean HbA1c was associated with lower limit in target HbA1c and being
      "less agreeable." Clinicians who were more demanding and dogmatic appeared to
      have better outcomes.

PMID- 29573085
TI  - Radiomics strategy for glioma grading using texture features from multiparametric
      MRI.
AB  - BACKGROUND: Accurate glioma grading plays an important role in the clinical
      management of patients and is also the basis of molecular stratification
      nowadays. PURPOSE/HYPOTHESIS: To verify the superiority of radiomics features
      extracted from multiparametric MRI to glioma grading and evaluate the grading
      potential of different MRI sequences or parametric maps. STUDY TYPE:
      Retrospective; radiomics. POPULATION: A total of 153 patients including 42, 33,
      and 78 patients with Grades II, III, and IV gliomas, respectively. FIELD
      STRENGTH/SEQUENCE: 3.0T MRI/T1 -weighted images before and after contrast
      enhanced, T2 -weighted, multi-b-value diffusion-weighted and 3D arterial spin
      labeling images. ASSESSMENT: After multiparametric MRI preprocessing, high
      throughput features were derived from patients' volumes of interests (VOIs). The
      support vector machine-based recursive feature elimination was adopted to find
      the optimal features for low-grade glioma (LGG) vs. high-grade glioma (HGG), and
      Grade III vs. IV glioma classification tasks. Then support vector machine (SVM)
      classifiers were established using the optimal features. The accuracy and area
      under the curve (AUC) was used to assess the grading efficiency. STATISTICAL
      TESTS: Student's t-test or a chi-square test were applied on different clinical
      characteristics to confirm whether intergroup significant differences exist.
      RESULTS: Patients' ages between LGG and HGG groups were significantly different
      (P < 0.01). For each patient, 420 texture and 90 histogram parameters were
      derived from 10 VOIs of multiparametric MRI. SVM models were established using 30
      and 28 optimal features for classifying LGGs from HGGs and grades III from IV,
      respectively. The accuracies/AUCs were 96.8%/0.987 for classifying LGGs from
      HGGs, and 98.1%/0.992 for classifying grades III from IV, which were more
      promising than using histogram parameters or using the single sequence MRI. DATA
      CONCLUSION: Texture features were more effective for noninvasively grading
      gliomas than histogram parameters. The combined application of multiparametric
      MRI provided a higher grading efficiency. The proposed radiomic strategy could
      facilitate clinical decision-making for patients with varied glioma grades. LEVEL
      OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1518
      1528.

PMID- 29573087
TI  - Reaction of B2 (o-tol)4 with CO and Isocyanides: Cleavage of the C=O Triple Bond
      and Direct C-H Borylations.
AB  - The reaction of highly Lewis acidic tetra(o-tolyl)diborane(4) with CO afforded a
      mixture of boraindane and boroxine by the cleavage of the C=O triple bond. 13 C
      labeling experiments confirmed that the carbon atom in the boraindane stems from
      CO. Simultaneously, formation of boroxine 3 could be considered as borylene
      transfer to capture the oxygen atom from CO. The reaction of diborane(4) with t
      Bu-NC afforded an azaallene, while the reaction with Xyl-NC furnished cyclic
      compounds by direct C-H borylations.

PMID- 29573086
TI  - Electrochemical Measurement of Dopamine Release and Uptake in Zebrafish Following
      Treatment with Carboplatin.
AB  - Post-chemotherapy cognitive impairment, also known as 'chemobrain,' is a
      neurological condition in which cognitive function is impaired as a result of
      cancer chemotherapy treatment. In this work, we used fast-scan cyclic voltammetry
      (FSCV) to measure electrically evoked dopamine release and uptake in whole brain
      preparations from zebrafish that have been treated with carboplatin, an agent
      associated with chemobrain. We administered carboplatin by addition to the fish's
      tank water or their food. One week of treatment with 100 MUM carboplatin in the
      water was needed to significantly impair dopamine release (~40 % of control);
      however, only one day of treatment through the zebrafish's food was needed to
      cause a similar impairment. Atomic absorption spectroscopy measurements suggested
      that administration through food resulted in higher initial levels of carboplatin
      compared to water administration, but water administration resulted in an
      increase over time. Uptake, determined by modeling stimulated release plots, was
      unaffected. These results are consistent with our previous findings of diminished
      neurotransmitter release in rats and support a role for zebrafish in chemobrain
      related studies.

PMID- 29573088
TI  - Sensitivity cycling in physically dormant seeds of the Neotropical tree Senna
      multijuga (Fabaceae).
AB  - Cycling of sensitivity to physical dormancy (PY) break has been documented in
      herbaceous species. However, it has not been reported in tree seeds, nor has the
      effect of seed size on sensitivity to PY-breaking been evaluated in any species.
      Thus, the aims of this study were to investigate how PY is broken in seeds of the
      tropical legume tree Senna multijuga, if seeds exhibit sensitivity cycling and if
      seed size affects induction into sensitivity. Dormancy and germination were
      evaluated in intact and scarified seeds from two collections of S. multijuga. The
      effects of temperature, moisture and seed size on induction of sensitivity to
      dormancy-breaking were assessed, and seasonal changes in germination and
      persistence of buried seeds were determined. Reversal of sensitivity was also
      investigated. Fresh seeds were insensitive to dormancy break at wet-high
      temperatures, and an increase in sensitivity occurred in buried seeds after they
      experienced low temperatures during winter (dry season). Temperatures <=20 
      degrees C increased sensitivity, whereas temperatures >=30  degrees C decreased
      it regardless of moisture conditions. Dormancy was broken in sensitive seeds by
      incubating them at 35  degrees C. Sensitivity could be reversed, and large seeds
      were more sensitive than small seeds to sensitivity induction. Seeds of S.
      multijuga exhibit sensitivity cycling to PY-breaking. Seeds become sensitive
      during winter and can germinate with the onset of the spring-summer rainy season
      in Brazil. Small seeds are slower to become sensitive than large ones, and this
      may be a mechanism by which germination is spread over time. Sensitive seeds that
      fail to germinate become insensitive during exposure to drought during summer.
      This is the first report of sensitivity cycling in a tree species.

PMID- 29573089
TI  - How to do the 'peritoneal slit': extracting the sleeve gastrectomy made simple!

PMID- 29573090
TI  - Charge Transport between Coupling Colloidal Perovskite Quantum Dots Assisted by
      Functional Conjugated Ligands.
AB  - Long alkyl-chain capping ligands are indispensable for preparing stable colloidal
      quantum dots. However, its insulating feature blocks efficient carrier transport
      among QDs, leading to inferior performance in light-emitting diodes (LEDs). The
      trade-off between conductivity and colloidal stability of QDs has now been
      overcome. Methylamine lead bromide (MAPbBr3 ) QDs with a conjugated alkyl-amine,
      3-phenyl-2-propen-1-amine (PPA), as ligands were prepared. Owing to electron
      cloud overlapping and the delocalization effect of conjugated molecules, the
      conductivity and carrier mobility of PPA-QDs films increased almost 22 times over
      that of OA-QD films without compromising colloidal stability and
      photoluminescence. PPA-QDs LEDs exhibit a maximum current efficiency of 9.08 cd A
      1 , which is 8 times of that of OA-QDs LEDs (1.14 cd A-1 ). This work provides
      critical solution for the poor conductivity of QDs in applications of energy
      related devices.

PMID- 29573091
TI  - Novel approach to functional SNPs discovery from genome-wide data reveals
      promising variants for colon cancer risk.
AB  - In the majority of colorectal cancer (CRC) cases, the genetic basis of
      predisposition remains unexplained. The goal of the study was to assess the
      regulatory SNPs (rSNPs) in the human genome and to reveal SRC drivers based on
      the available chromatin immunoprecipitation sequencing (ChIP-Seq, ChIA-PET) and
      transcriptional profiling (RNA-Seq) data. We combined positional (locations
      within genome regulatory elements) and functional (associated with allele
      specific binding and expression) criteria followed by an analysis using genome
      wide association studies (GWAS) and minor allele frequency (MAF) datasets. DeSeq2
      analysis through 70 CRC patients reinforced the regulatory potential. rSNPs
      (1,476) that were associated with significant (P < 0.01) allele-specific events
      resulting in thirty that exhibited a link with CRC according to the MAF and 27,
      with a risk of malignancy in general according to GWAS. Selected rSNPs may modify
      the expression of genes for tumor suppressors and the regulators of signaling
      pathways, including noncoding RNAs. However, the rSNPs from the most represented
      group affect the expression of genes related to splicing. Our findings strongly
      suggest that the identified variants might contribute to CRC susceptibility,
      which indicates that aberrant splicing is one of the key mechanisms for
      unraveling disease etiopathogenesis and provides useful inputs for interpreting
      how genotypic variation corresponds to phenotypic outcome.

PMID- 29573092
TI  - Biosynthesis of the Polycyclic System in the Antifungal HSAF and Analogues from
      Lysobacter enzymogenes.
AB  - The biocontrol agent Lysobacter enzymogenes produces polycyclic tetramate
      macrolactams (PoTeMs), including the antifungal HSAF. To elucidate the
      biosynthesis of the cyclic systems, we identified eleven HSAF
      precursors/analogues with zero, one, two, or three rings through heterologous
      expression of the HSAF gene cluster. A series of combinatorial gene expression
      and deletion experiments showed that OX3 is the "gatekeeper" responsible for the
      formation of the first 5-membered ring from lysobacterene A, OX1 and OX2 are
      responsible for formation of the second ring but with different selectivity, and
      OX4 is responsible for formation of the 6-membered ring. In vitro experiments
      showed that OX4 is an NADPH-dependent enzyme that catalyzes the reductive
      cyclization of 3-dehydroxy alteramide C to form 3-dehydroxy HSAF. Thus, the
      multiplicity of OX genes is the basis for the structural diversity of the HSAF
      family, which is the only characterized PoTeM cluster that involves four redox
      enzymes in the formation of the cyclic system.

PMID- 29573093
TI  - Sorting of Arabidopsis NRAMP3 and NRAMP4 depends on adaptor protein complex AP4
      and a dileucine-based motif.
AB  - Adaptor protein complexes mediate cargo selection and vesicle trafficking to
      different cellular membranes in all eukaryotic cells. Information on the role of
      AP4 in plants is still limited. Here, we present the analyses of Arabidopsis
      thaliana mutants lacking different subunits of AP4. These mutants show
      abnormalities in their development and in protein sorting. We found that growth
      of roots and etiolated hypocotyls, as well as male fertility and trichome
      morphology are disturbed in ap4. Analyses of GFP-fusions transiently expressed in
      mesophyll protoplasts demonstrated that the tonoplast (TP) proteins MOT2, NRAMP3
      and NRAMP4, but not INT1, are partially sorted to the plasma membrane (PM) in the
      absence of a functional AP4 complex. Moreover, alanine mutagenesis revealed that
      in wild-type plants, sorting of NRAMP3 and NRAMP4 to the TP requires an N
      terminal dileucine-based motif. The NRAMP3 or NRAMP4 N-terminal domain containing
      the dileucine motif was sufficient to redirect the PM localized INT4 protein to
      the TP and to confer AP4-dependency on sorting of INT1. Our data show that
      correct sorting of NRAMP3 and NRAMP4 depends on both, an N-terminal dileucine
      based motif as well as AP4.

PMID- 29573094
TI  - Iridium-Catalyzed Aerobic Coupling of Salicylaldehydes with Alkynes: A Remarkable
      Switch of Oxacyclic Product.
AB  - The iridium(III)/copper(II)-catalyzed dehydrogenative coupling of
      salicylaldehydes with internal alkynes proceeds efficiently under atmospheric
      oxygen through aldehyde C-H bond cleavage and decarbonylation. A variety of
      benzofuran derivatives can be synthesized by the environmentally benign
      procedure. DFT calculations suggest that this unique transformation involves the
      facile deinsertion of CO in the key metallacycle intermediate, which is in marked
      contrast to the corresponding rhodium(III) catalysis that leads to CO-retentive
      chromone derivatives.

PMID- 29573095
TI  - Myoepithelial carcinoma of the nasopharynx: Rare case report with
      clinicopathologic and immunohistochemical features review of literature.
AB  - BACKGROUND: Myoepithelial carcinoma is a rare salivary carcinoma, which most
      often arises from the major salivary glands. Only a few cases of myoepithelial
      carcinoma of the nasopharynx have been reported, thus, the treatment guideline
      and prognosis remain undefined. METHODS: We reported a case of nasopharyngeal
      myoepithelial carcinoma in a 31-year-old man. The tumor cells showed specific
      cell types and arrangements histologically, which were immunoreactive with
      myoepithelial markers. The patient received surgical excision with transpalatal
      approach. A literature review of previous cases was also presented. RESULTS: The
      patient reflected residual tumor 4 weeks later. After concurrent
      chemoradiotherapy (CRT), the tumor reduced and remained stable without signs of
      progression. CONCLUSION: The nasopharyngeal mass with spindled, plasmacytoid,
      epithelioid, and clear cell types, was suggested to raise the suspicion of
      myoepithelial carcinoma in order to diagnose and treat early. The wide surgical
      excision followed by optimal adjuvant therapy might offer a mode of treatment
      with better survival results.

PMID- 29573096
TI  - Electrochemical Responsive Superhydrophilic Surfaces of Polythiophene Derivatives
      towards Cell Capture and Release.
AB  - Highly efficient cell capture and release with low background are urgently
      required for early diagnosis of diseases such as cancer. Herein, we report an
      electrochemical responsive superhydrophilic surface exhibiting specific cell
      capture and release with high yields and extremely low nonspecific adhesion.
      Through electrochemical deposition, 3-substituted thiophene derivatives are
      deposited onto indium tin oxide (ITO) nanowire arrays with 4-n
      nonylbenzeneboronic acid (BA) as dopant, fabricating the electrochemical
      responsive superhydrophilic surfaces. The molecular recognition between sialic
      acids over-expressed on the cell membrane and doped BAs endows the
      electrochemical responsive surfaces with the ability to capture and release
      targeted cancer cells. By adjusting the substituent group of thiophene
      derivatives, the surface wettability can be readily regulated and further
      utilized for reducing nonspecific cell adhesion. Significantly, the released
      cells still maintain a high proliferation ability, which indicates that the
      applied potential does not significantly harm the cells. Therefore, these results
      may provide a new strategy to achieve advanced functions of biomedical materials,
      such as low nonspecific adhesion.

PMID- 29573097
TI  - Ultrastable Imine-Based Covalent Organic Frameworks for Sulfuric Acid Recovery:
      An Effect of Interlayer Hydrogen Bonding.
AB  - A rapid and scalable synthesis of six new imine-linked highly porous and
      crystalline COFs is presented that feature exceptionally high chemical stability
      in harsh environments including conc. H2 SO4 (18 m), conc. HCl (12 m), and NaOH
      (9 m). This is because of the presence of strong interlayer C-H???N hydrogen
      bonding among the individual layers, which provides significant steric hindrance
      and a hydrophobic environment around the imine (-C=N-) bonds, thus preventing
      their hydrolysis in such an abrasive environment. These COFs were further
      converted into porous, crystalline, self-standing, and crack-free COF membranes
      (COFMs) with extremely high chemical stability for their potential applications
      for sulfuric acid recovery. The as-synthesized COFMs exhibit unprecedented
      permeance for acetonitrile (280 Lm-2  h-1  bar-1 ) and acetone (260 Lm-2  h-1 
      bar-1 ).

PMID- 29573098
TI  - Rosiglitazone lowers resting and blood pressure response to exercise in men with
      type 2 diabetes: A 1-year randomized study.
AB  - AIMS: We aimed to determine the effect of 1-year treatment with the insulin
      sensitizer peroxisome proliferator-activated receptor (PPAR)-gamma agonist
      rosiglitazone on exercise capacity and blood pressure (BP) response to exercise
      in men with coronary artery disease (CAD) and type 2 diabetes (T2D). MATERIALS
      AND METHODS: A total of 116 men (age, 64 +/- 7 years; body mass index, 30.0 +/-
      4.4 kg/m2 ) with CAD and T2D were randomized to receive rosiglitazone or placebo
      for 1 year. Exercise capacity (VO2peak ) and BP response to exercise were
      assessed with a maximal treadmill test, prior to the intervention and at 1-year
      follow-up. Exercise-induced hypertension (EIH) was defined as maximal systolic BP
      >= 220 mm Hg and/or diastolic BP >= 100 mm Hg. RESULTS: PPAR-gamma agonist
      treated patients showed improvements in fasting glucose, HbA1c and insulin
      sensitivity (Homeostasis model assessment of insulin resistance [HOMA-IR]) (all P
      < .05). Resting BPs, maximal exercise diastolic BP and resting rate-pressure
      product (RPP) were all reduced in the PPAR-gamma agonist group (P < .05). Maximal
      exercise duration was unchanged. T2D patients who displayed the greatest
      improvement in insulin sensitivity (HOMA-IR) under PPAR-gamma agonist treatment
      experienced a greater reduction in exercise BP and RPP (P < .05). The proportion
      of men with EIH decreased in the PPAR-gamma agonist group during follow-up
      (39.00% +/- 0.06% vs 21.00% +/- 0.05%). In the subgroup with EIH that was treated
      with a PPAR-gamma agonist, resting and exercise diastolic BP, as well as resting
      RPP, were all reduced at 1-year follow-up (P < .05). CONCLUSIONS: The insulin
      sensitizer rosiglitazone has a beneficial effect on resting and BP response to
      exercise in men with CAD and T2D, especially in those with an exaggerated BP
      response to exercise.

PMID- 29573099
TI  - Nursing history as philosophy-towards a critical history of nursing.
AB  - Mainstream nursing history often positions itself in opposition to philosophy and
      many nursing historians are reticent of theorizing. In the quest to illuminate
      the lives of nurses and women current historical approaches are driven by
      reformist aspirations but are based on the conception that nursing or caring is
      basically good and the timelessness of universal values. This has the effect of
      essentialising political categories of identity such as class, race and gender.
      This kind of history is about affirmation rather than friction and about the
      conservation of memory and musealization. In contrast, we will focus on how we
      imagine nursing history could be used as a philosophical, critical perspective to
      challenge the ongoing transformations of our societies. Existing reality must be
      confronted with strangeness and the historically different can assume the
      function of this counterpart, meaning present and past must continuously be set
      in relation to each other. Thus, critical history is always the history of the
      present but not merely the pre-history of the present - critique must rather
      present different realities and different certainties. In this paper, we use this
      approach to discuss the implementation of the nursing process (NP) in Germany.
      The nursing process appears to be a technology that helped to set up an
      infrastructure - or assemblage - to transform nursing interventions into a
      commodity exchangable between consumers and nurses in a free market. In our
      theoretical perspective, we argue that NP was a step in the realization of the
      German ordoliberal program, a specific variety of neoliberalism. In order to
      implement market-orientation in the healthcare system it was necessary to
      transform hospitals into calculable spaces and to make all performances in the
      hospital calculable. This radically transformed not just the systems, but the
      ways in which nurses and patients conveived of themselves.

PMID- 29573100
TI  - Trimethylsilyl-Protected Alkynes as Selective Cross-Coupling Partners in Titanium
      Catalyzed [2+2+1] Pyrrole Synthesis.
AB  - Trimethylsilyl (TMS)-protected alkynes served as selective alkyne cross-coupling
      partners in titanium-catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS
      protected alkynes with internal alkynes and azobenzene under the catalysis of
      titanium imido complexes yielded pentasubstituted 2-TMS-pyrroles with greater
      than 90 % selectivity over the other nine possible pyrrole products. The steric
      and electronic effects of the TMS group were both identified to play key roles in
      this highly selective pyrrole synthesis. This strategy provides a convenient
      method to synthesize multisubstituted pyrroles as well as an entry point for
      further pyrrole diversification through facile modification of the resulting 2
      silyl pyrrole products, as demonstrated through a short formal synthesis of the
      marine natural product lamellarin R.

PMID- 29573101
TI  - Improving life expectancy of patients with scleroderma: results from the South
      Australian Scleroderma Register.
AB  - BACKGROUND: Scleroderma is a rare connective tissue disorder characterised by
      inflammation, vasculopathy and excessive fibrosis. Patients with scleroderma are
      known to have decreased life expectancy. AIM: To investigate changes in life
      expectancy in patients with scleroderma over a 30-year period. METHODS: Utilising
      the South Australian Scleroderma Register, deceased patients were identified. We
      examined changes in age of death and duration of disease in these patients over
      three time periods: 1985-1994, 1995-2004 and 2005-2015. Analyses of scleroderma
      subtypes were performed, and comparisons were made to the general South
      Australian population. RESULTS: A total of 413 deceased patients was identified.
      Females were overrepresented 315 to 98; 265 had limited scleroderma, 90 diffuse
      and 22 overlap disease. Over 30 years, the mean age of death improved from 66.4
      to 74.5 years (P < 0.001). Duration of disease improved from 12.1 to 22.9 years
      (P < 0.001). Improvement in survival was seen in limited (P = 0.001), diffuse (P
      = 0.04) and overlap (P = 0.04) subgroups. The increase in survival was only seen
      for female (9.8 +/- 4.2 years) but not male (1.4 +/- 6.7 years) patients.
      CONCLUSION: Over the last 30 years, survival has significantly improved for
      female but not male patients. As no disease-modifying drugs have consistently
      been shown to alter disease course, this improvement is likely attributable to
      general improvements in medical care, including that of scleroderma-related
      complications. While the life expectancy for limited disease is now close to that
      of the general population, patients with diffuse and overlap disease continue to
      suffer from significant early mortality.

PMID- 29573103
TI  - Efficacy and adverse effects of topical chloramphenicol ointment use for surgical
      wounds: a systematic review.
AB  - BACKGROUND: Chloramphenicol ointment is often used in plastic and dermatologic
      surgery as a topical antibiotic for surgical wounds, but evidence regarding its
      efficacy and side effects is lacking. In addition, anecdotal fear of aplastic
      anaemia exists from the oral use of this drug. We performed a systematic review
      of the literature to assess the efficacy and side effect profile of topical
      chloramphenicol ointment on non-ocular surgical wounds. METHODS: A systematic
      search of MEDLINE, EMBASE and the Cochrane Library from inception until 4
      September 2017 was undertaken. Clinical studies of topical chloramphenicol
      ointment use on surgical wounds were included. Studies looking only at ocular use
      or those not available in full text or English were excluded. The review was
      conducted adhering to PRISMA guidelines. RESULTS: After full-text review, five
      articles were included. Two were randomized controlled trials, one was
      retrospective case control and two were case studies. There was evidence that
      chloramphenicol ointment use on surgical wounds produced a non-statistically
      significant reduction in infection rates. Delayed hypersensitivity and acute
      oesophagitis were noted as potential side effects of non-ocular topical use.
      Aplastic anaemia was not reported. CONCLUSION: There is a paucity of clinical
      data regarding the use of topical chloramphenicol ointment on surgical wounds.
      Further randomized controlled trials may be beneficial in order to support or
      refute its use in this setting.

PMID- 29573102
TI  - Day case hernia repair: weak evidence or practice gap?
AB  - BACKGROUND: Analysis of a private insurer's administrative data set revealed
      significant variation in the length of hospital stay following hernia surgery.
      OBJECTIVES: This review examined factors influencing the performance of day
      surgery for inguinal, femoral and umbilical hernia repair in adults. DATA
      SOURCES: A systematic literature search was conducted in the PubMed, Embase and
      Cochrane Library databases to identify studies and clinical practice guidelines
      (CPGs) comparing same day hernia surgery to surgery followed by an overnight
      stay. REVIEW METHODS: Screening of studies by abstract and full text was
      completed by a single researcher and checked by a second. Studies were selected
      for inclusion based on a step-wise approach across three phases. RESULTS: Limited
      evidence from one systematic review, and three case series studies including 3213
      patients found that same day hernia surgery was as safe and effective as an
      overnight stay. All identified CPGs recommended a same day procedure for most
      patients. Two case series studies reported that 3-8% of patients were ineligible
      for day procedures due to medical reasons; however, the characteristics of
      patients, in general, which are not suitable, have not been adequately
      investigated. CONCLUSIONS: Day surgery for groin hernia repair is safe and
      effective for most patients. However, evidence-based support is only one of many
      factors that may contribute to the uptake of day surgery in Australia. There is
      an opportunity for key stakeholders across the private healthcare system to
      deliver an equally effective but more sustainable and affordable hernia care by
      increasing the day surgery rates.

PMID- 29573104
TI  - Transvesical robot-assisted simple prostatectomy with 360 degrees 
      circumferential reconstruction: step-by-step technique.
AB  - OBJECTIVE: To present the step-by-step technique of a 360 degrees  mucosal
      reconstruction after transvesical robot-assisted simple prostatectomy (RASP).
      PATIENT AND METHODS: We analysed the first 23 consecutive patients who underwent
      RASP using our 360 degrees  reconstruction between December 2015 and October
      2017. After transperitoneal intravesical adenoma enucleation, a circumferential
      360 degrees  reconstruction is performed. The first suture is placed at the 9
      o'clock position and the edge of the urethra and bladder mucosa is approximated
      using 2-0 barbed suture. The reconstruction is continued counter-clockwise and
      the bladder mucosa is approximated to the urethra circumferentially. RESULTS: The
      mean (sd) operating time was 160.6 (28.1) min and the estimated blood loss was
      98.6 (99.8) mL. No patients required conversion to open surgery. No intra
      operative or postoperative transfusions were needed. No intra-operative
      complications occurred. The mean (sd) length of hospital stay was 2.1 (0.6) days.
      One postoperative complication was reported (respiratory distress in a patient
      with chronic obstructive pulmonary disease, requiring intensive care unit
      admission). CONCLUSION: Our 360 degrees  reconstruction during RASP is feasible
      and safe. The aim of the technique is to minimize use of electrocautery and
      decrease the raw surface area on the prostate capsule. This technical
      modification could potentially lessen postoperative bleeding after RASP and
      therefore the need for continuous bladder irrigation. In addition, it could
      potentially lead to mitigation of burning and irritative postoperative symptoms.
      Longer follow-up and comparative studies of different RASP techniques are still
      needed.

PMID- 29573105
TI  - What to do with the rectal stump during sphincter preserving rectal cancer
      resection with end colostomy: a collaborative snapshot study.
AB  - AIM: Low Hartmann's resection (LHR) and intersphincteric abdominoperineal
      excision (iAPR) are both feasible options in the treatment of rectal cancer when
      restoration of bowel continuity is not desired. The aim of this study was to
      compare the incidence of pelvic abscess and associated need for re-intervention
      and readmission after LHR and iAPR. METHOD: From a snapshot research project in
      which all rectal cancer resections from 71 Dutch hospitals in 2011 were
      evaluated, patients who underwent LHR or iAPR were selected. RESULTS: A total of
      185 patients were included: 139 LHR and 46 iAPR. No differences in baseline
      characteristics were found except for more multivisceral resections in the iAPR
      group (22% vs 10%; P = 0.041). Pelvic abscesses were diagnosed in 17% of the LHR
      group after a median of 21 days (interquartile range 10-151 days), compared to
      11% in the iAPR group (P = 0.352) after a median of 90 days (interquartile range
      44-269 days; P = 0.102). All 28 patients with a pelvic abscess underwent at least
      one re-intervention. Four patients (9%) in the iAPR group and nine (7%) after LHR
      were readmitted because of a pelvic abscess over a median 39 months of follow-up.
      CONCLUSION: This cross-sectional multicentre study suggests that cross-stapling
      and intersphincteric resection of the rectal stump, during non-restorative rectal
      cancer resection, are associated with an equal risk of pelvic abscess formation
      and have a similar need for re-intervention and readmission.

PMID- 29573106
TI  - The effect of low-intensity extracorporeal shockwave therapy in an obesity
      associated erectile dysfunction rat model.
AB  - OBJECTIVES: To investigate the feasibility of the Zucker fatty (ZF) rat as a
      model for research in to obesity-associated erectile dysfunction (OAED) and to
      determine the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT)
      on penile tissue and function in these rats. MATERIALS AND METHODS: Eight new
      born male Zucker lean (ZL group) rats (ZUC-Leprfa 186) and 16 new-born male ZF
      rats (ZUC-Leprfa 185) were injected with 5-ethynyl-2'-deoxyuridine (EdU) at birth
      to identify and monitor endogenous stem cells. Insulin tolerance testing was
      performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were
      kept as controls, and the remaining eight ZF rats were treated with Li-ESWT (0.02
      mJ/mm2 , 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1
      week washout period, erectile function was evaluated by measuring intracavernosal
      pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then
      harvested for histological study to assess smooth muscle/collagen content and
      endothelium content in the corpora cavernosum. LipidTOXTM staining was used to
      evaluate lipid accumulation. EdU, as a marker of cell activation, and
      phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.
      RESULTS: The ICP/MAP indicated that erectile function was severely impaired in
      the ZF group as compared with the ZL group. In the ZF + SW group, erectile
      function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF
      group, while Li-ESWT increased the muscle content in ZF + SW group. Moreover, the
      penile endothelium was damaged in the ZF group, and Li-ESWT enhanced the
      regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid
      accumulation was seen in the penile tissue of ZF rats. Li-ESWT significantly
      reduced both the amount and the distribution pattern of LipidTOX, suggesting
      decreased overall lipid infiltration. Furthermore, Li-ESWT increased EdU-positive
      cells and markedly enhanced the phosphorylation level of H3P at Ser-10 in the ZF
      + SW group. Most H3P-positive cells were located within smooth muscle cells, with
      some located in the endothelium suggesting that these tissues are the reservoirs
      of penile stem/progenitor cells. CONCLUSION: ZF rats can serve as an animal model
      in which to study OAED. This study reveals that obesity impairs erectile function
      by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation
      in the corpus cavernosum. Li-ESWT restored penile haemodynamic parameters in the
      ZF rats by restoring smooth muscle and endothelium content and reducing lipid
      accumulation. The underlying mechanism of Li-ESWT appears to be activation of
      stem/progenitor cells, which prompts cellular proliferation and accelerates
      penile tissue regeneration. Our findings are of interest, not just as a
      validation of this emerging treatment for erectile dysfunction, but also as a
      novel and potentially significant method to modulate endogenous stem/progenitor
      cells in other disease processes.

PMID- 29573107
TI  - Reply to Glancy et al.

PMID- 29573108
TI  - Metronidazole following excisional haemorrhoidectomy: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Post-operative pain is a major issue following excisional
      haemorrhoidectomy. Although metronidazole by both oral and topical administration
      routes has been shown to reduce pain after haemorrhoidectomy, its use remains a
      contentious issue. This systematic review and meta-analysis aims to investigate
      the effect of metronidazole on post-operative pain after excisional
      haemorrhoidectomy. METHODS: A systematic review of the literature was conducted
      according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Randomized controlled trials (RCTs) published in PubMed/MEDLINE,
      EMBASE, CENTRAL and CINAHL, from inception to December 2016 were retrieved. The
      primary outcome investigated was post-operative pain reported as visual analogue
      score (VAS). Secondary outcomes were analgesia use, complications and time to
      return to normal activity. Meta-analysis was performed using Review Manager
      version 5.3 software. RESULTS: Nine randomized controlled trials including 523
      patients were included in the final analysis. Five studies used oral
      administration and four used topical. Meta-analysis showed that post-operative
      VAS of patients receiving metronidazole by either route was significantly less
      than those in comparison groups. VAS means decreased at all the time points for
      both oral and topical metronidazole. Topical and oral routes of administration
      were not compared in any study. There was no increase in complication rates and
      return to normal activity was significantly earlier for patients receiving
      metronidazole (-4.49 days; 95% confidence interval [-7.70, -1.28]; P = 0.006).
      CONCLUSIONS: Both topical and oral metronidazole reduce post-operative pain
      without an increase in complication rates and result in an earlier return to
      normal activity. Further work is required to determine which the optimum route of
      administration is.

PMID- 29573109
TI  - Management of chronic pain and opioid dependence with buprenorphine/naloxone.

PMID- 29573110
TI  - SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes:
      A systematic review and meta-analysis.
AB  - To assess the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2)
      inhibitors plus a dipeptidyl peptidase-4 (DPP-4) inhibitor in patients with type
      2 diabetes mellitus (T2DM), we performed a systematic review and meta-analysis of
      14 randomized controlled trials (RCTs) involving 4828 patients. Compared with a
      DPP-4 inhibitor, SGLT2 inhibitor/DPP-4 inhibitor combination therapy was
      significantly associated with a decrease in glycaemic control (HbA1c, -0.71%;
      fasting plasma glucose [FPG], -25.62 mg/dL; postprandial plasma glucose, -44.00
      mg/dL), body weight (-2.05 kg) and systolic blood pressure (-5.90 mm Hg), but an
      increase in total cholesterol (TC) of 3.24%, high-density lipoprotein of 6.15%
      and low-density lipoprotein of 2.55%. Adding a DPP-4 inhibitor to an SGLT2
      inhibitor could reduce HbA1c by -0.31%, FPG by -8.94 mg/dL, TC by -1.48% and
      triglycerides by -3.25%. Interestingly, low doses of an SGLT2 inhibitor in the
      combination has similar or even better efficacy in some aspects than high doses.
      Similar adverse events were observed for the combination therapy, with the
      exception of genital infection vs DPP-4 inhibitor (risk ratio [RR], 5.31) and
      consistent genital infection vs an SGLT2 inhibitor (RR, 0.61). Further studies
      are warranted to confirm these results.

PMID- 29573111
TI  - A tale of two cities: prehospital intubation with or without paralysing agents
      for traumatic brain injury.
AB  - BACKGROUND: The role of prehospital endotracheal intubation (PETI) for traumatic
      brain injury is unclear. In Victoria, paramedics use rapid sequence induction
      (RSI) drugs to facilitate PETI, while in New South Wales (NSW) they do not have
      access to paralysing agents. We hypothesized that RSI would both increase PETI
      rates and improve mortality. METHODS: Retrospective comparison of adult primary
      admissions (Glasgow Coma Scale <9 and abbreviated injury scale head and neck >2)
      to either Victorian or NSW trauma centre, which were compared with univariate and
      logistic regression analysis to estimate odds ratio for mortality and intensive
      care unit (ICU) length of stay. RESULTS: One hundred and ninety-two Victorian and
      91 NSW patients did not differ in: demographics (males: 77% versus 79%; P = 0.7
      and age: 34 (18-88) versus 33 (18-85); P = 0.7), Glasgow Coma Scale (3 (3-8)
      versus 5 (3-8); P = 0.07), and injury severity score (38 (26-75) versus 35 (18
      75); P = 0.09), prehospital hypotension (15.4% versus 11.7%; P = 0.5) and
      desaturation (14.6% versus 17.5%; P = 0.5). Victorians had higher abbreviated
      injury scale head and neck (5 (4-5) versus 5 (3-6); P = 0.04) and more often
      successful PETI (85% versus 22%; P < 0.05). On logistic regression analysis,
      mortality did not differ among groups (31.7% versus 26.3%; P = 0.34; OR = 0.84;
      95% CI: 0.38-1.86; P = 0.67). Among survivors, Victorians had longer stay in ICU
      (364 (231-486) versus 144 (60-336) h), a difference that persisted on gamma
      regression (effect = 1.58; 95% CI: 1.30-1.92; P < 0.05). CONCLUSION: Paramedics
      using RSI to obtain PETI in patients with traumatic brain injury had a higher
      success rate. This increase in successful PETI rate was not associated with an
      improvement in either mortality rate or ICU length of stay.

PMID- 29573112
TI  - Isolated colonic hernia through the oesophageal hiatus causing gastric outlet
      obstruction.

PMID- 29573113
TI  - Relapse prevention in anorexia nervosa: Experiences of patients and parents.
AB  - One of the main aims of treatment after successful recovery from anorexia nervosa
      (AN) is to prevent a relapse. The Guideline Relapse Prevention (GRP) Anorexia
      Nervosa offers a structured approach to relapse prevention. This study explores
      how patients and their parents experience working with the guideline. It also
      describes the factors that support or hinder successful application of the
      guideline. A descriptive qualitative research design was chosen involving in
      depth interviews with seventeen patients with anorexia nervosa and six sets of
      parents. Patients and family members were generally satisfied with the support
      provided by the GRP. It contributed significantly to a better understanding of
      the personal process of relapse. Patients and families valued being able to keep
      in touch with their professional during the aftercare programme. The GRP supports
      the patient's use of self-management strategies for relapse prevention.

PMID- 29573114
TI  - MiR-127-3p inhibits cell growth and invasiveness by targeting ITGA6 in human
      osteosarcoma.
AB  - Osteosarcoma (OS) is one of the most universal malignant bone tumors that occur
      mostly in children and adolescents. This study aimed to investigate the roles of
      miR-127-3p and integrin subunit-alpha 6 (ITGA6) in OS proliferation, apoptosis,
      invasion and migration, and to explore the possible molecular mechanism and
      target relationship. By conducting quantitative real-time polymerase chain
      reaction (qRT-PCR) and western blot, the microRNA (miRNA) and protein expressions
      of miR-127-3p and ITGA6 in both tissues and cells were determined. The expression
      of apoptosis and migration related were also detected by western blot. The target
      relationship between miR-127-3p and ITGA6 was predicted by TargetScan and
      verified by dual-luciferase reporter assay. The biological functions of miR-127
      3p and ITGA6 in OS were investigated by following experiments: cell counting kit
      8 (CCK-8) and colony formation assays to inspect cell proliferation, flow
      cytometry, and caspase 3 activity assay to examine apoptosis, and transwell and
      wound healing assays to analyze invasion and migration. Significant down
      regulation of miR-127-3p and up-regulation of ITGA6 was found out in OS tissues
      and cells. ITGA6 was proved to be the downstream target gene of miR-127-3p and
      functioned as a tumor promotor in OS, while miR-127-3p restrained deterioration
      of OS by suppressing cell viability, reducing migration and invasion, and
      promoting apoptosis. MiR-127-3p suppressed proliferation, invasion, and migration
      while stimulated apoptosis of OS cells through knocking down ITGA6. (c) 2018
      IUBMB Life, 70(5):411-419, 2018.

PMID- 29573115
TI  - Accuracy and consistency of electronic root canal length determination with
      electrically isolating rubber stoppers.
AB  - The aim of this study was to investigate the influence of an isolating silicone
      stopper on the measuring accuracy and display consistency of three electrometric
      apex locators. The length of the canal to the major foramen was determined
      electrometrically using an ISO size 10 file in 20 extracted teeth each with
      natural crowns (Group I), amalgam fillings (Group II) or base-metal crowns (Group
      III), The measurements were performed with isolating or conventional silicone
      stoppers using three different apex locators with a four-level scale consistency
      rating. The use of isolating stoppers resulted in a more consistent display than
      with conventional stoppers, independent of the presence or type of coronal
      restoration (P = 0.017). Across all coronal restorations, the position of the
      major foramen could be determined to within +/- 0.5 mm without significant
      differences (P = 0.79) using conventional and isolating stoppers. The use of
      modified isolating stoppers provides a significant increase in display
      consistency.

PMID- 29573116
TI  - Impacts of persistent general and site-specific pain on activities of daily
      living and physical performance: A prospective analysis of the English
      Longitudinal Study of Ageing.
AB  - AIM: Pain is an increasingly common phenomenon as people age; pain over a long
      period can result in limited functioning. The present study investigated the
      impacts of general and multisite-specific pain on activities of daily living and
      physical performance among older adults. METHODS: Data were analyzed from the
      English Longitudinal Study of Ageing, a representative sample of the population
      aged >=50 years. Face-to-face interview and nurse records were used from waves 2
      6 (2004-2012) for analyses. General and site-specific pain (back, hip and knee)
      were measured biennially between 2004 and 2008 (n = 5010). Impaired activity of
      daily living and physical performance measures (chair rise and grip strength)
      between 2008 and 2012 were aggregated across assessments as outcomes. Multinomial
      logistic regressions were used for the former and linear regression for the
      latter, adjusting for potential covariates. RESULTS: General pain (moderate-to
      severe) was prevalent, with close to one-quarter of participants reporting pain
      at least twice during the follow-up period. Multisite pain reports were strong
      predictors of subsequent limited activities of daily living (adjusted odds ratio
      range 1.86-3.97 for back and hip, 2.04-4.19 for back and knee, and 2.08-5.16 for
      hip and knee). Persistent pain was also strongly associated with worse physical
      performance outcomes. CONCLUSIONS: Our data confirm the longitudinal impacts of
      persistent pain among older adults. The findings highlight the value of
      monitoring and management of both general and site-specific pain in order to
      promote sustained independence at older ages. Geriatr Gerontol Int 2018; 18: 1051
      1057.

PMID- 29573117
TI  - Taking parents seriously: The experiences of parents with a son or daughter in
      adult medium secure forensic mental health care.
AB  - Adult forensic mental health services provide care and treatment to individuals
      with complex offending and mental health histories. However, little attention has
      been paid to the parents of those receiving care within them. This research
      explored the experiences of parents with an adult son or daughter with mental
      illness in a medium secure mental health unit. Transcripts from semi-structured
      interviews were analysed using interpretative phenomenological analysis. This led
      to the identification of three superordinate themes: 'Something's not right'
      onset of mental distress; 'It's a terrible battle'-relating with professionals;
      and 'A very sad fact of life'-caring with no end in sight were identified which
      together contained nine subordinate themes. The onset of the mental distress was
      narrated as overwhelming, frightening, and confusing with experiences of
      violence. Services were seen as invalidating, and interactions with them
      characterized as a battle. Poor information and involvement were a common
      experience. Whilst diagnosis was a relief to some, the ongoing sense of loss and
      burden were clear. Staying connected and hopes for the future were also
      described. It is clear from this study that mental health services need to do
      more to engage and foster trust with parents from the outset and to offer support
      for this group. If secure services were to view parents as 'forensic carers',
      this may help improve respect and engagement between services and carers.
      Services and policymakers should strive to foster high-quality family involvement
      as part of developing social inclusion.

PMID- 29573118
TI  - SGLT2 inhibitors and risk of stroke in patients with type 2 diabetes: A
      systematic review and meta-analysis.
AB  - The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on risk of
      stroke have not been conclusively established. Therefore, we conducted a meta
      analysis to evaluate the effects of SGLT2 inhibitors on stroke risk in patients
      with type 2 diabetes mellitus (T2DM) by searching available randomized trials in
      PubMed, Embase, CENTRAL, Web of Science, Scopus and ClinicalTrials.gov databases.
      We identified 32 eligible trials involving 75 540 participants. The incidence of
      stroke in groups receiving SGLT2 inhibitor monotherapy or combination therapy did
      not differ significantly from that in control groups, with a relative risk (RR)
      of 1.01 and 1.0, respectively. Three SGLT2 inhibitors were tested, with similar
      RR values (canagliflozin [RR, 0.91], dapagliflozin [RR, 0.99] and empagliflozin
      [RR, 1.03]). Subgroup analyses showed that RR values were not affected by gender,
      age, diabetes duration, BMI or HbA1C levels, but Black patients had a lower
      incidence of stroke than White or Asian patients. This meta-analysis indicated
      that SGLT2 inhibitor therapy did not increase stroke incidence, and no
      significant differences in stroke risk were observed among 3 SGLT2 inhibitors
      (class effect). However, the small racial disparity requires further study and
      confirmation.

PMID- 29573119
TI  - Determine and compare the viewpoints of nurses, patients and their relatives to
      workplace violence against nurses.
AB  - AIM: The present study aims to assess the perception of nurses, patients and
      their relatives regarding the nature of workplace violence against nurses.
      BACKGROUND: Workplace violence adversely affects the health, well-being and
      safety of nurses and the quality of nursing care. METHODS: In the present
      descriptive comparative study, the nature of violence was assessed using a
      modified and validated International Labor Office, the International Council of
      Nurses, World Health Organization, and Public Services International
      Questionnaire. RESULTS: Nurses, patients and relatives reported verbal abuse as
      the most common and sexual violence as the least common type of violence against
      nurses. Nurses mostly blamed factors associated with patients and their relatives
      as the cause of violence, whereas patients and their relatives blamed social
      factors. CONCLUSIONS: This study shows that violence is significantly prevalent
      in clinical settings, but its nature is differently perceived by nurses, patients
      and their relatives. This phenomenon requires further studies because knowledge
      of the causes of this difference could help to reduce and control violence.
      IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary that nursing managers inform
      nurses about protocols for reporting all such cases in order to collect
      information, and based on a clear procedure, actively pursue reported cases and
      take the necessary measures to prevent violence against nurses.

PMID- 29573120
TI  - The biologically active zone in upland habitats at the Hanford Site, Washington,
      USA: Focus on plant rooting depth and biomobilization.
AB  - We challenge the suggestion by Sample et al. (2015) that a depth of 305 cm (10
      ft) exceeds the depth of biological activity in soils at the Hanford Site,
      Washington, USA, or similar sites. Instead, we support the standard point of
      compliance, identified in the Model Toxics Control Act in the state of
      Washington, which specifies a depth of 457 cm (15 ft) for the protection of both
      human and ecological receptors at the Hanford Site. Our position is based on
      additional information considered in our expanded review of the literature, the
      influence of a changing environment over time, plant community dynamics at the
      Hanford Site, and inherent uncertainty in the Sample et al. (2015) analysis.
      Integr Environ Assess Manag 2018;14:442-446. (c) 2018 SETAC.

PMID- 29573121
TI  - Head and neck cancer reirradiation with interstitial high-dose-rate
      brachytherapy.
AB  - BACKGROUND: As high-dose-rate (HDR) brachytherapy can preferentially spare normal
      anatomic structures surrounding the radiation target, we report on our experience
      using this technique in head and neck cancer reirradiation. METHODS: Twenty
      patients received HDR brachytherapy reirradiation with curative or palliative
      intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial
      outcomes were calculated using Kaplan-Meier analysis. RESULTS: For curative
      treatment, actuarial 2-year rates of local control and overall survival (OS) were
      73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was
      seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage
      resection showed a trend toward improved local control and OS (P = .069 and P =
      .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities.
      CONCLUSION: Curative-intent HDR brachytherapy reirradiation can provide excellent
      local control and encouraging OS. Given the late toxicity rates, patient
      selection is essential, with particular utility for younger patients or those
      treated with salvage resection.

PMID- 29573122
TI  - Peritoneal carcinomatosis or something else?

PMID- 29573123
TI  - The association between psychological factors and breastfeeding behaviour in
      women with a body mass index (BMI) >=30 kg m-2 : a systematic review.
AB  - Breastfeeding can play a key role in the reduction of obesity, but initiation and
      maintenance rates in women with a body mass index (BMI) of >=30 kg m-2 are low.
      Psychological factors influence breastfeeding behaviours in the general
      population, but their role is not yet understood in women with a BMI >=30 kg m-2
      . Therefore, this review aimed to systematically search and synthesize the
      literature, which has investigated the association between any psychological
      factor and breastfeeding behaviour in women with a BMI >=30 kg m-2 . The search
      identified 20 eligible papers, reporting 16 psychological factors. Five
      psychological factors were associated with breastfeeding behaviours: intentions
      to breastfeed, belief in breast milk's nutritional adequacy and sufficiency,
      belief about other's infant feeding preferences, body image and social knowledge.
      It is therefore recommended that current care should encourage women to plan to
      breastfeed, provide corrective information for particular beliefs and address
      their body image and social knowledge. Recommendations for future research
      include further exploration of several psychological factors (i.e. expecting that
      breastfeeding will enhance weight loss, depression, anxiety and stress) and
      evidence and theory-based intervention development.

PMID- 29573124
TI  - The role of lipids in host-pathogen interactions.
AB  - Innate immunity relies on the effective recognition and elimination of pathogenic
      microorganisms. This entails sequestration of pathogens into phagosomes that
      promptly acquire microbicidal and degradative properties. This complex series of
      events, which involve cytoskeletal reorganization, membrane remodeling and the
      activation of multiple enzymes, is orchestrated by lipid signaling. To overcome
      this immune response, intracellular pathogens acquired mechanisms to subvert
      phosphoinositide-mediated signaling and use host lipids, notably cholesterol, as
      nutrients. We present brief overviews of the role of phosphoinositides in
      phagosome formation and maturation as well as of cholesterol handling by host
      cells, and selected Salmonella, Shigella, Chlamydia and Mycobacterium
      tuberculosis to exemplify the mechanisms whereby intracellular pathogens co-opt
      lipid metabolism in host cells. (c) 2018 IUBMB Life, 70(5):384-392, 2018.

PMID- 29573125
TI  - Risk of dipeptidyl peptidase-4 (DPP-4) inhibitors on site-specific cancer: A
      systematic review and meta-analysis.
AB  - The long-term impact of dipeptidyl peptidase-4 (DPP-4) inhibition is unknown, and
      there are concerns about the influence of DPP-4 inhibition on carcinogenesis of
      the pancreas and thyroid. As DPP-4 is a rather unselective enzyme present in many
      tissues, we focused on all specific cancer types. PubMed and EMBASE were searched
      between January 2005 and April 2017 to identify studies comparing DPP-4
      inhibitors with either placebo or active drugs on cancer risk. Studies were
      included if they reported on at least one specific cancer outcome and had a
      follow-up of at least 1 year after start of drug use. Methodological quality of
      the studies was assessed by the Cochrane Collaboration's tool and the Newcastle
      Ottawa Scale. Twenty-five studies met the inclusion criteria (12 randomized
      controlled trials and 13 observational studies). Sample sizes of the DPP-4
      inhibitor groups ranged from 29 to 8212 patients for randomized controlled trials
      and from 2422 to 71 137 patients for observational studies. Mean age ranged from
      51 to 76 years, and mean follow-up was 1.5 years. None of the pooled
      (sensitivity) analyses, except the observational studies studying breast cancer
      (hazard ratio [95% CI]: 0.76 [0.60-0.96]), showed evidence for an association
      between DPP-4 inhibitors and site-specific cancer. Also for pancreatic and
      thyroid cancer, no statistically significant risk was found. Based on the current
      literature, it is not possible to conclude whether DPP-4 inhibitors were
      associated with an increased risk of site-specific cancer. Future studies should
      address the methodological limitations and follow patients for a longer period to
      determine the long-term cancer risk of DPP-4 inhibitors.

PMID- 29573126
TI  - The influence of thyroid function on the coagulation system and its clinical
      consequences.
AB  - Several studies indicate that low plasma levels of thyroid hormone shift the
      hemostatic system towards a hypocoagulable and hyperfibrinolytic state, whereas
      high levels of thyroid hormone lead to more coagulation and less fibrinolysis.
      Low levels of thyroid hormone thereby seem to lead to an increased bleeding risk,
      whereas high levels, by contrast, increase the risk of venous thromboembolism.
      Hypothyroidism leads to a higher incidence of acquired von Willebrand's syndrome
      and with increasing levels of free thyroxine, levels of fibrinogen, factor VIII
      and von Willebrand factor, amongst others, increase gradually, to the extent that
      they may lead to symptomatic venous thromboembolism in patients with
      hyperthyroidism. Here, we discuss the literature on the effect of thyroid hormone
      on the hemostatic system and the associated risk of bleeding and venous
      thromboembolism. Patients with hypothyroidism are at increased risk of developing
      bleeding complications, which could be relevant in patients undergoing invasive
      procedures. Furthermore, physicians should be aware of the possibility of
      hyperthyroidism as an underlying risk factor for venous thromboembolism,
      especially in unexplained cases. Clinical studies are needed to further
      investigate the significance for general practice of these findings. Besides the
      effects of hyperthyroidism on venous thromboembolism, its effects on embolism
      secondary to atrial fibrillation are described.

PMID- 29573127
TI  - Bridges of biomaterials promote nigrostriatal pathway regeneration.
AB  - Repair of central nervous system (CNS) lesions is difficulted by the lack of
      ability of central axons to regrow, and the blocking by the brain astrocytes to
      axonal entry. We hypothesized that by using bridges made of porous biomaterial
      and permissive olfactory ensheathing glia (OEG), we could provide a scaffold to
      permit restoration of white matter tracts. We implanted porous polycaprolactone
      (PCL) bridges between the substantia nigra and the striatum in rats, both with
      and without OEG. We compared the number of tyrosine-hydroxylase positive (TH+)
      fibers crossing the striatal-graft interface, and the astrocytic and microglial
      reaction around the grafts, between animals grafted with and without OEG.
      Although TH+ fibers were found inside the grafts made of PCL alone, there was a
      greater fiber density inside the graft and at the striatal-graft interface when
      OEG was cografted. Also, there was less astrocytic and microglial reaction in
      those animals. These results show that these PCL grafts are able to promote
      axonal growth along the nigrostriatal pathway, and that cografting of OEG
      markedly enhances axonal entry inside the grafts, growth within them, and re
      entry of axons into the CNS. These results may have implications in the treatment
      of diseases such as Parkinson's and others associated with lesions of central
      white matter tracts. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 2018.

PMID- 29573128
TI  - Changes in self-efficacy associated with success in quitting smoking in
      participants in Japanese smoking cessation therapy.
AB  - AIMS: To identify the strength of self-efficacy during 12-week smoking cessation
      therapy (SCT) that consisted of 5 sessions and its association with the success
      of smoking cessation at the end of SCT. BACKGROUND: Few studies showed to what
      level self-efficacy should be reinforced to facilitate success in smoking
      cessation. DESIGN: Prospective cohort study. METHODS: We enrolled 488 smokers who
      received SCT from 6 Japanese smoking cessation clinics between October 2008 and
      October 2014. In each smoker, the self-efficacy of quitting smoking was assessed
      at each session of SCT. The association of the strength of self-efficacy with the
      success of smoking cessation was investigated by logistic regression analysis
      adjusting for age, gender, having a present illness, prescription, and nicotine
      dependence score. RESULTS: The self-efficacy of the 398 abstainers was
      significantly higher than that of the 90 nonabstainers at the first to fifth
      sessions of the SCT (P < .001 each). Participants with self-efficacy scores of
      greater than 60% were significantly more likely to attain abstinence than those
      with scores of 40% and less. CONCLUSION: During SCT, nurses' counselling to
      maintain patients' self-efficacy scores of smoking cessation in the range from
      61% to 100% may be important for assisting patients in achieving smoking
      cessation.

PMID- 29573129
TI  - Effect of periodontal ligament removal with gauze prior to delayed replantation
      in rabbit incisors on rate of replacement resorption.
AB  - BACKGROUND/AIM: Delayed (dry storage > 60 minutes) replantation results in
      ankylosis and replacement resorption. It has been suggested to remove the non
      viable periodontal ligament before replantation to possibly reduce the rate of
      replacement resorption. However there has been no study on the rate of
      replacement resorption after such measures. The aim of this study was to
      investigate if there was any difference in the rate of replacement resorption by
      either removing the periodontal ligament (PDL) with gauze or not removing PDL in
      teeth subjected to delayed replantation followed by healing for 2 or 6 weeks.
      MATERIALS AND METHODS: Maxillary central incisors were extracted in 8 rabbits. In
      the right central incisors, the necrotic PDL was removed by dry gauze over the
      root surface. In the left eight extracted teeth PDL was left on the root surface.
      All extracted teeth were left to dry for 60 minutes. Extra-oral root canal
      treatment was performed before replantation. The rabbits were sacrificed after 2
      weeks and 6 weeks respectively. Histologic processing and evaluation was done.
      RESULTS: In the 2 weeks group, all teeth showed ankylosis. The cementum was
      intact, and fusion of the bone and root was generally seen without resorption of
      the root, whereas in the 6 weeks group regardless of whether PDL had been kept or
      not, ankylosis and osseous replacement of the dentin was seen. There was no
      evidence of inflammatory infiltrate in the sections examined. CONCLUSION: Removal
      of PDL prior to delayed replantation may result in some initial protection of the
      cementum during the first few weeks. However, over longer times there seems to be
      neither protection of the dentin from ankylosis and osseous replacement, nor any
      influence on the rate of replacement resorption.

PMID- 29573130
TI  - Biomimetic design of bone substitutes based on cuttlefish bone-derived
      hydroxyapatite and biodegradable polymers.
AB  - Being a major component of bone tissue, hydroxyapatite is the most investigated
      calcium phosphate in the design and development of bone implants. The high
      brittleness and poor load-bearing properties have led researchers to manipulate
      hydroxyapatite performance by applying polymer or metal materials. The present
      study focuses on biomimetic approach of the hydroxyapatite synthesis from the
      cuttlefish bone in order to preserve highly porous structure. The low stiffness
      of hydroxyapatite scaffold was altered by thin polycaprolactone/poly(lactic acid)
      coating, resulting in remarkably 18-fold increase of Young's modulus. The
      mechanical test revealed that poly(lactic acid) increases the stiffness of
      composite scaffolds which depends on the polycaprolactone/poly(lactic acid)
      volume ratio. The composite scaffolds are bioactive supporting the deposition of
      new calcium phosphates when incubated in simulated physiological medium for 21
      days. Moreover, the culture of human embryonic kidney cells indicated non
      cytotoxicity of the composite scaffolds with emphasis on the cell proliferation
      during three days of culture. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29573131
TI  - Achieving Sustained Virological Response in Liver Transplant Recipients With
      Hepatitis C Decreases Risk of Decline in Renal Function.
AB  - The effect of antiviral therapy (AVT) on kidney function in liver transplantation
      (LT) recipients has not been well described despite known association of
      hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared
      the incidence of CKD and end-stage renal disease (ESRD) in 204 LT recipients with
      HCV based on treatment response to AVT. The mean estimated glomerular filtration
      rate (eGFR) at baseline (3 months after LT) was similar in the sustained
      virological response (SVR; n = 145) and non-SVR group (n = 59; 69 +/- 21 versus
      65 +/- 33 mL/minute/1.73 m2 ; P = 0.27). In the unadjusted Cox proportional
      regression analysis, the presence of SVR was associated with an 88% lower risk of
      CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05-0.31) and 86% lower
      risk of ESRD (odds ratio, 0.14; 95% CI, 0.05-0.35). Similar results were found
      after adjusting for propensity score and time-dependent Cox regression analyses.
      The estimated slopes of eGFR based on a 2-stage mixed model of eGFR were
      calculated. Patients with SVR had a less steep slope in eGFR (-0.60
      mL/minute/1.73 m2 /year; 95% CI, -1.50 to 0.30; P = 0.190) than recipients
      without SVR (-2.53 mL/minute/1.73 m2 /year; 95% CI, -3.99 to -1.07; P = 0.001),
      and the differences in the slopes were statistically significant (P = 0.026). In
      conclusion, in LT recipients with chronic HCV infection, achieving SVR
      significantly lowers the risk of decline in renal function and progression to
      ESRD independent of the AVT therapy used.

PMID- 29573132
TI  - Effects of different etching modes on the nanoleakage of universal adhesives: A
      systematic review and meta-analysis.
AB  - PURPOSE: The aim of this systematic review was to evaluate how etching modes
      affect the nanoleakage of universal adhesive from in vitro studies. MATERIALS AND
      METHODS: PubMed/MEDLINE, Web of Science, Scopus and Science Direct electronic
      databases were searched for in vitro studies that evaluated the nanoleakage of
      universal adhesives. A total of 511 (after duplicate removal) potentially
      relevant records were identified in the literature search. The titles and
      abstracts of the retrieved studies were screened by two independent researchers
      according to the main concept. Subsequently, the full text of potentially
      relevant studies was screened using the exclusion criteria. Thirteen studies were
      subjected to qualitative analysis, and 5 of them were selected for a detailed
      meta-analysis. RESULTS: Seven universal adhesives were evaluated in this review.
      The meta-analysis demonstrated that the etch-and-rinse technique significantly
      reduced the nanoleakage of the Peak Universal and G-Bond Plus adhesives, whereas
      the self-etch mode reduced the nanoleakage of All-Bond Universal. In comparison,
      the etching technique did not significantly alter the nanoleakage of either
      Prime&Bond Elect or Scotchbond Universal which was characterized by the smallest
      nanoleakage. CONCLUSIONS: Etching modes significantly, in various ways, influence
      the nanoleakage of universal adhesives. CLINICAL SIGNIFICANCE: Contrary to the
      drive to simplify bonding technologies, an appreciation of their adhesive
      components and how these perform according to bonding technique could yield a
      knowledge-based practical approach that ultimately improves the longevity of
      direct composite restorations.

PMID- 29573134
TI  - Magnetoelastic galfenol as a stent material for wirelessly controlled degradation
      rates.
AB  - The gold standard of care for coronary artery disease, a leading cause of death
      for in the world, is balloon angioplasty in conjunction with stent deployment.
      However, implantation injuries and long-term presence of foreign material often
      promotes significant luminal tissue growth, leading to a narrowing of the artery
      and severely restricted blood flow. A promising method to mitigate this process
      is the use of biodegradable metallic stents, but thus far they have either
      degraded too slowly (iron) or disappeared prematurely (magnesium). The present
      work investigates the use of a unique type of magnetic material, galfenol (iron
      gallium), for postoperative wireless control of stent degradation rates. Due to
      its magnetoelastic property, galfenol experiences longitudinal micron-level
      elongations when exposed to applied magnetic fields, allowing generation of a
      microstirring effect that affect its degradation behavior. In vitro indirect
      cytotoxicity tests on primary rat aortic smooth muscle cells indicated that
      galfenol byproducts must be concentrated approximately seven times from collected
      60 day degradation medium to cause ~15% of death from all cells. Surface and
      cross-sectional characterization of the material indicate that galfenol (Fe80
      Ga20 ) degradation rates (~0.55% per month) are insufficient for stenting
      applications. While this material may not be ideal for comprising the entire
      stent, there is potential for use in combination with other materials.
      Furthermore, the ability to control degradation rates postimplantation opens new
      possibilities for biodegradable stents; additional magnetoelastic materials
      should be investigated for use in stenting applications. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29573133
TI  - Lipid packing defects and membrane charge control RAB GTPase recruitment.
AB  - Specific intracellular localization of RAB GTPases has been reported to be
      dependent on protein factors, but the contribution of the membrane
      physicochemical properties to this process has been poorly described. Here, we
      show that three RAB proteins (RAB1/RAB5/RAB6) preferentially bind in vitro to
      disordered and curved membranes, and that this feature is uniquely dependent on
      their prenyl group. Our results imply that the addition of a prenyl group confers
      to RAB proteins, and most probably also to other prenylated proteins, the ability
      to sense lipid packing defects induced by unsaturated conical-shaped lipids and
      curvature. Consistently, RAB recruitment increases with the amount of lipid
      packing defects, further indicating that these defects drive RAB membrane
      targeting. Membrane binding of RAB35 is also modulated by lipid packing defects
      but primarily dependent on negatively charged lipids. Our results suggest that a
      balance between hydrophobic insertion of the prenyl group into lipid packing
      defects and electrostatic interactions of the RAB C-terminal region with charged
      membranes tunes the specific intracellular localization of RAB proteins.

PMID- 29573135
TI  - Interaction of spirodiclofen with insecticides for the control of Brevipalpus
      yothersi in citrus.
AB  - BACKGROUND: The mite Brevipalpus yothersi (Acari: Tenuipalpidae) is of great
      importance in citriculture because it is a vector of the disease citrus leprosis.
      The frequency of application of a combination of pesticides has increased because
      of an increase in the occurrence of economically important pests of citrus.
      However, the combined effect of acaricide and other insecticides targeting B.
      yothersi is unknown. The objective of this study was to evaluate the effect of a
      combination of spirodiclofen and other insecticides on the control of B.
      yothersi. RESULTS: Analysis using spirodiclofen alone resulted in 97.22%
      efficiency in the control of B. yothersi on day 7 after application. A
      combination of spirodiclofen with either phosmet or imidacloprid resulted in 55%
      and 59% efficiency, respectively. A reduction in the efficiency of mite control
      by up to 42% was observed when the mites were exposed to a combination of
      acaricide with other insecticides. CONCLUSIONS: Application of a combination of
      spirodiclofen with phosmet or imidacloprid compromises the efficiency of
      acaricide in the control of B. yothersi. (c) 2018 Society of Chemical Industry.

PMID- 29573136
TI  - Adsorbed hollow fiber-based biological fingerprinting for the discovery of
      platelet aggregation inhibitors from Danshen-Honghua decoction.
AB  - For lead compound discovery from natural products, hollow fiber cell fishing with
      chromatographic analysis is a newly developed method. In this study, an adsorbed
      hollow fiber-based biological fingerprinting method was firstly developed to
      discover potential platelet aggregation inhibitors from Danshen-Honghua
      decoction. Platelets were seeded on the fiber and their survival rate was tested.
      Results indicated that more than 92% platelets survived during the whole
      operation process. Ranitidine and tirofiban were used as positive and negative
      control respectively to verify the reliability of the presented approach. The
      main variables such as amount of extract and stirring time that affect the
      adsorbed hollow fiber-based biological fingerprinting process were optimized, and
      the repeatability of this method was also investigated. Finally, 12 potential
      active compounds in Danshen-Honghua decoction were successfully detected using
      the established approach and structures for nine of them were tentatively
      identified by liquid chromatography with mass spectrometry analysis. In addition,
      the in vitro platelet aggregation inhibition test was carried out for five of the
      nine hit compounds, and three active components, namely, lithospermic acid,
      salvianolic acid A, and salvianolic acid B were confirmed. These results proved
      that the proposed method could be an effective approach for screening platelet
      inhibitors from plant extracts.

PMID- 29573137
TI  - Heterozygosity for the alpha-1-antitrypsin Z allele in cirrhosis is associated
      with more advanced disease.
AB  - Alpha-1-antitrypsin deficiency (A1ATD) due to homozygosity for the Z allele (ZZ)
      is an established risk factor for cirrhosis, but the liver disease risk in
      heterozygous Z allele carriers (MZ) is controversial. The aim of the present
      study was to determine the prevalence of the MZ genotype among patients with
      cirrhosis and the associated risk of decompensation and liver
      transplantation/mortality. An unselected cohort of 561 patients with cirrhosis
      and 248 deceased liver donors were genotyped for the A1ATD risk alleles Z and S
      using a validated allelic discrimination assay. Clinical and biochemical
      parameters were assessed in 488 genotype MM and 52 MZ patients at baseline when
      cirrhosis was diagnosed and at the last contact, before liver transplantation or
      death, as study endpoints. MZ prevalence was 2.8% among liver donors, 5.8%, 9.1%,
      10.9%, and 19.0% in patients with cirrhosis and Model for End-Stage Liver Disease
      sodium (MELD-Na) <=10, 11-20, 21-30, and >30, respectively. Among liver
      transplant recipients, MZ prevalence was 9.7%. MS prevalence was not different
      between donors, patients with cirrhosis, or transplant recipients. At the end of
      follow-up, MELD-Na scores were higher among heterozygous Z risk allele carriers
      (16 versus 19; P = 0.03). Decompensation of cirrhosis with ascites or
      encephalopathy was significantly more frequent in patients with MZ than in MM
      patients. In the subgroup with transferrin (Tf) saturation >50% or Tf <180 mg/dL,
      MZ patients had a significantly higher risk of liver transplantation or death
      than MM patients. In conclusion, the genotype MZ is a genetic risk factor for
      more advanced cirrhosis and decompensation. MZ patients with cirrhosis and
      hypotransferrinemia or increased Tf saturation are at higher risk of death and
      liver transplantation. Liver Transplantation 24 744-751 2018 AASLD.

PMID- 29573138
TI  - High Electromagnetic Field Enhancement of TiO2 Nanotube Electrodes.
AB  - We present the fabrication of TiO2 nanotube electrodes with high biocompatibility
      and extraordinary spectroscopic properties. Intense surface-enhanced resonance
      Raman signals of the heme unit of the redox enzyme Cytochrome b5 were observed
      upon covalent immobilization of the protein matrix on the TiO2 surface, revealing
      overall preserved structural integrity and redox behavior. The enhancement factor
      could be rationally controlled by varying the electrode annealing temperature,
      reaching a record maximum value of over 70 at 475  degrees C. For the first time,
      such high values are reported for non-directly surface-interacting probes, for
      which the involvement of charge-transfer processes in signal amplification can be
      excluded. The origin of the surface enhancement is exclusively attributed to
      enhanced localized electric fields resulting from the specific optical properties
      of the nanotubular geometry of the electrode.

PMID- 29573139
TI  - Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone,
      or dapagliflozin alone added to metformin monotherapy in subgroups of patients
      with type 2 diabetes in the DURATION-8 randomized controlled trial.
AB  - This analysis assessed whether responses with exenatide once weekly plus
      dapagliflozin (n = 231), exenatide once weekly alone (n = 230), or dapagliflozin
      alone (n = 233) differed in key patient subpopulations of the DURATION-8 trial.
      Potential treatment-by-subgroup interactions for changes in glycated haemoglobin
      (HbA1c) and body weight after 28 weeks were evaluated among subgroups determined
      by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race,
      ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly
      plus dapagliflozin reduced HbA1c and body weight across all subgroups: least
      squares mean reductions ranged from -8.4 to -26.1 mmol/mol (-0.77% to -2.39%) for
      HbA1c and from -2.07 to -4.55 kg for body weight. Potential treatment-by-subgroup
      interactions (P < .10) were found for HbA1c change by age (P = .016) and eGFR (P
      = .097). Age subgroup analysis findings were not consistent with expected
      mechanistic effects, with the small number of patients aged >=65 years (n = 74 vs
      n = 499 for patients aged <65 years) limiting the interpretability of the
      interaction term. In the exenatide once weekly plus dapagliflozin and
      dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions
      were greater among patients with eGFR >=90 vs >=60 to <90 mL/min/1.73 m2 (least
      squares mean reductions of -23.6 vs -19.0 mmol/mol [-2.16% vs -1.74%], -17.3 vs 
      12.0 mmol/mol [-1.58% vs -1.10%], and -17.7 vs -16.9 mmol/mol [-1.62% vs -1.55%]
      for the respective treatments); this was consistent with the mechanism of action
      of dapagliflozin. A potential treatment-by-subgroup interaction was observed for
      change in body weight by sex (P = .099), with greater weight loss for women vs
      men across all treatments (range -2.56 to -3.98 kg vs -0.56 to -2.99 kg). In
      conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c
      and body weight across all patient subgroups and was more effective than
      exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.

PMID- 29573140
TI  - Quantitative analysis of image quality for acceptance and commissioning of an MRI
      simulator with a semiautomatic method.
AB  - Magnetic Resonance Imaging (MRI) simulation differs from diagnostic MRI in
      purpose, technical requirements, and implementation. We propose a semiautomatic
      method for image acceptance and commissioning for the scanner, the radiofrequency
      (RF) coils, and pulse sequences for an MRI simulator. The ACR MRI accreditation
      large phantom was used for image quality analysis with seven parameters. Standard
      ACR sequences with a split head coil were adopted to examine the scanner's basic
      performance. The performance of simulation RF coils were measured and compared
      using the standard sequence with different clinical diagnostic coils. We used
      simulation sequences with simulation coils to test the quality of image and
      advanced performance of the scanner. Codes and procedures were developed for
      semiautomatic image quality analysis. When using standard ACR sequences with a
      split head coil, image quality passed all ACR recommended criteria. The image
      intensity uniformity with a simulation RF coil decreased about 34% compared with
      the eight-channel diagnostic head coil, while the other six image quality
      parameters were acceptable. Those two image quality parameters could be improved
      to more than 85% by built-in intensity calibration methods. In the simulation
      sequences test, the contrast resolution was sensitive to the FOV and matrix
      settings. The geometric distortion of simulation sequences such as T1-weighted
      and T2-weighted images was well-controlled in the isocenter and 10 cm off-center
      within a range of +/-1% (2 mm). We developed a semiautomatic image quality
      analysis method for quantitative evaluation of images and commissioning of an MRI
      simulator. The baseline performances of simulation RF coils and pulse sequences
      have been established for routine QA.

PMID- 29573141
TI  - A multicenter investigation of respiratory syncytial viral infection in children
      with hematopoietic cell transplantation.
AB  - BACKGROUND: Hematopoietic cell transplant (HCT) may be a risk factor for
      morbidity and mortality from respiratory syncytial virus (RSV). Previous studies
      have been limited by small sample size. We took a multicenter approach with the
      goal of better understanding the epidemiology, risk factors, treatment,
      morbidity, and mortality associated with RSV infections among children with HCT
      in the United States. METHODS: A retrospective, multicenter, cohort study of
      pediatric HCT recipients were diagnosed with RSV infection between January 2010
      and December 2014. RESULTS: Of the 1522 HCT, 47 (3%) patients were diagnosed with
      RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care
      unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died.
      Prophylactic palivizumab was uncommon. All who required critical care received
      ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were
      found in 16 patients and were not associated with the need for critical care. We
      examined potential risk factors for severity of RSV disease. In those who
      received invasive ventilation, 100% had one of the preidentified risk factors.
      Half of those requiring mechanical ventilation were diagnosed with RSV during
      their conditioning for transplant as opposed to only 2.4% of those that did not
      require invasive mechanical ventilation (P = .005). CONCLUSIONS: In this
      multicenter cohort, RSV was not common in children following HCT. Few children
      infected with RSV required critical care and mortality was low. Those diagnosed
      with RSV during conditioning for transplant were at higher risk for invasive
      mechanical ventilation.

PMID- 29573142
TI  - Development of an unbiased, semi-automated approach for classifying plasma cell
      immunophenotype following multicolor flow cytometry of bone marrow aspirates.
AB  - BACKGROUND: Despite increased usage of multiparameter flow cytometry (MFC) to
      assess diagnosis, prognosis, and therapeutic efficacy (minimal residual disease,
      MRD) in plasma cell neoplasms (PCNs), standardization of methodology and data
      analysis is suboptimal. We investigated the utility of using the mean and median
      fluorescence intensities (FI) obtained from MFC to objectively describe
      parameters that distinguish plasma cell (PC) phenotypes. METHODS: In this
      retrospective study, flow cytometry results from bone marrow aspirate specimens
      from 570 patients referred to the Myeloma Institute at UAMS were evaluated. Mean
      and median FI data were obtained from 8-color MFC of non-neoplastic, malignant,
      and mixed PC populations using antibodies to CD38, CD138, CD19, CD20, CD27, CD45,
      CD56, and CD81. RESULTS: Of 570 cases, 252 cases showed only non-neoplastic PCs,
      168 showed only malignant PCs, and 150 showed mixed PC populations. Statistical
      analysis of median FI data for each CD marker showed no difference in expression
      intensity on non-neoplastic and malignant PCs, between pure and mixed PC
      populations. ROC analysis of the median FI of CD expression in non-neoplastic and
      malignant PCs was used to develop an algorithm to convert quantitative FI values
      to qualitative assessments including "negative," "positive," "dim," and
      "heterogeneous" expression. CONCLUSIONS: FI data derived from 8-color MFC can be
      used to define marker expression on PCs. Translation of FI data from Infinicyt
      software to an Excel worksheet streamlines workflow and eliminates
      transcriptional errors when generating flow reports. (c) 2018 International
      Clinical Cytometry Society.

PMID- 29573143
TI  - The safety and efficacy of quadrivalent live attenuated influenza vaccine in
      Japanese children aged 2-18 years: Results of two phase 3 studies.
AB  - BACKGROUND: Quadrivalent live attenuated influenza vaccine (Q/LAIV) has not been
      assessed in Japanese children. OBJECTIVES: Evaluate safety and efficacy of Q/LAIV
      in Japanese children. PATIENTS/METHODS: Two phase 3 studies were conducted in the
      2014-2015 influenza season. Study 1 was an open-label, uncontrolled single arm,
      multicenter study of Q/LAIV safety in subjects aged 2-6 years. Study 2 was a
      randomized, double-blind, placebo-controlled multicenter study of Q/LAIV safety
      and efficacy; subjects aged 7-18 years were randomized 2:1 to receive Q/LAIV or
      placebo. Primary efficacy endpoint was laboratory-confirmed symptomatic influenza
      infection caused by vaccine-matched strains; secondary endpoint evaluated
      efficacy against all strains regardless of match. Both studies reported solicited
      symptoms, adverse events (AEs), and serious AEs. RESULTS: In Study 1, 100
      subjects received Q/LAIV. In Study 2, 1301 subjects received Q/LAIV (n = 868) or
      placebo (n = 433). Treatment-emergent AEs occurred in 42% of subjects in Study 1,
      and in 24.3% of subjects in the Q/LAIV arm and in 25.9% of subjects in the
      placebo arm in Study 2. In Study 2, a single infection by a vaccine-matched
      strain was reported in the placebo arm, resulting in a vaccine efficacy estimate
      of 100% (95% CI: -1875.3, 100.0); efficacy for all strains regardless of match to
      the vaccine was 27.5% (95% CI: 7.4, 43.0). CONCLUSIONS: Quadrivalent live
      attenuated influenza vaccine did not meet its primary efficacy endpoint as only a
      single infection by a vaccine-matched strain was detected; however, efficacy for
      the secondary endpoint, all strains regardless of match, was achieved. Q/LAIV was
      generally well tolerated in the Japanese pediatric population.

PMID- 29573144
TI  - Relevance of the Thought-Shape Fusion Trait Questionnaire for healthy women and
      women presenting symptoms of eating disorders and mixed mental disorders.
AB  - Thought-shape fusion (TSF) describes the experience of marked concerns about body
      weight/shape, feelings of fatness, the perception of weight gain, and the
      impression of moral wrongdoing after thinking about eating fattening/forbidden
      foods. This study sets out to evaluate the short version of the TSF trait
      questionnaire (TSF). The sample consists of 315 healthy control women, 244 women
      with clinical and subthreshold eating disorders, and 113 women with mixed mental
      disorders (mixed). The factor structure of the TSF questionnaire was examined
      using exploratory and subsequent confirmatory factor analyses. The questionnaire
      distinguishes between a Concept scale and a Clinical Impact scale. However, a
      lack of measurement invariances refers to significant differences between groups
      in terms of factor loadings, thresholds, and residuals, which questions cross
      group validity. Results indicate that the concept is understood differently in
      the 3 groups and refers to the suitability of the questionnaire primarily for
      individuals presenting with symptoms of eating disorders.

PMID- 29573146
TI  - Self-care in Preserving the Vascular Network: Old Problem, New Challenge for the
      Medical Staff.
AB  - Teaching/educating patients with end stage renal disease (ESRD) and identifying
      their self-care behaviors for vascular network preservation are very important.
      However, the self-care behaviors regularly performed by patients are still
      unknown. We compared self-care behaviors for vascular network preservation
      performed by patients who are/are not followed-up by the nephrologist. The study
      design was a prospective, observational and comparative study. Inclusion criteria
      were as follows: ESRD patients (at stages 4 or 5); at least 18 years old; in pre
      dialysis with at least a 6-month follow-up period by the nephrologist or who
      started dialysis in emergency and were not followed-up by the nephrologist; with
      no memory problems; and medically stable. Primary outcome was the frequency of
      self-care behaviors for vascular network preservation. Secondary outcome was the
      comparison between self-care behaviors by ESRD patients who were/were not
      followed-up by the nephrologist. The study involved 145 patients, 64.1% were
      female, the mean age was 69.5 years and the self-care behaviors mean score was
      36.8% (with a SD of 39.8%). The number of patients followed-up and not followed
      up by the nephrologist was 109 (group 1) and 36 (group 2), respectively. Social
      characteristics were similar in the two groups (P > 0.05). The mean self-care
      behaviors were 29.4% and 59.2% in groups 1 and 2, respectively (P = 0.000).
      Patients performed self-care behaviors for vascular network preservation with a
      relatively low frequency (the mean score was 36.8% only). Patients not followed
      by the nephrologist performed self-care behaviors more often than those who were
      followed (59.2% vs. 29.4% respectively, P = 0.000).

PMID- 29573145
TI  - Profiling of m6A RNA modifications identified an age-associated regulation of
      AGO2 mRNA stability.
AB  - Gene expression is dynamically regulated in a variety of mammalian physiologies.
      During mammalian aging, there are changes that occur in protein expression that
      are highly controlled by the regulatory steps in transcription, post
      transcription, and post-translation. Although there are global profiles of human
      transcripts during the aging processes available, the mechanism(s) by which
      transcripts are differentially expressed between young and old cohorts remains
      unclear. Here, we report on N6-methyladenosine (m6A) RNA modification profiles of
      human peripheral blood mononuclear cells (PBMCs) from young and old cohorts. An
      m6A RNA profile identified a decrease in overall RNA methylation during the aging
      process as well as the predominant modification on proteincoding mRNAs. The m6A
      modified transcripts tend to be more highly expressed than nonmodified ones.
      Among the many methylated mRNAs, those of DROSHA and AGO2 were heavily methylated
      in young PBMCs which coincided with a decreased steady-state level of AGO2 mRNA
      in the old PBMC cohort. Similarly, downregulation of AGO2 in proliferating human
      diploid fibroblasts (HDFs) also correlated with a decrease in AGO2 mRNA
      modifications and steady-state levels. In addition, the overexpression of RNA
      methyltransferases stabilized AGO2 mRNA but not DROSHA and DICER1 mRNA in HDFs.
      Moreover, the abundance of miRNAs also changed in the young and old PBMCs which
      are possibly due to a correlation with AGO2 expression as observed in AGO2
      depleted HDFs. Taken together, we uncovered the role of mRNA methylation on the
      abundance of AGO2 mRNA resulting in the repression of miRNA expression during the
      process of human aging.

PMID- 29573147
TI  - Anxiolytic effect of anacardic acids from cashew (Anacardium occidentale) nut
      shell in mice.
AB  - Antianxiety drugs currently in use are associated with a number of serious side
      effects. Present study was designed to evaluate the efficacy of anacardic acids
      (AAs) isolated from cashew nut (Anacardium occidentale L.) shell liquid (CNSL) to
      treat anxiety as well as its role in oxidative stress in mice model. Anxiolytic
      effect of AA was evaluated using rota-rod and a set of behavioral tests in male
      Swiss albino mice at the doses of 10, 25, and 50 mg/kg. Flumazenil was used to
      evaluate the possible involvement of GABAergic system in the mechanism of action
      of AA. The effect of AA on oxidative stress in mice was evaluated by determining
      the concentration of malondialdehyde (MDA), reduced glutathione, and catalase
      (CAT) activity. The detection of DNA damage of the treated animals was performed
      using alkaline comet test in the hippocampus and frontal cortex of the animals.
      The results demonstrated that AA did not produce myorelaxant and sedative
      effects, nor did it cause a decrease in locomotor activity. The anxiolytic effect
      of AA was well-evident in all tests, especially at higher dose levels (25 and 50
      mg/mg). Flumazenil reversed the anxiolytic effect of AA at all doses. In
      addition, AA reduced oxidative stress by decreasing the concentration of MDA and
      increasing the levels of reduced glutathione (GSH) and CAT activity. Statistical
      analysis by Pearson's correlation indicated a positive correlation between
      anxiolytic effect of AA to its antioxidant and lipid peroxidation inhibitory
      activity. Furthermore, increased CAT activity and GSH concentrations in the
      hippocampus and frontal cortex of mice was also complementary to the reduced
      genotoxic damage observed in the study. In comet assay, AA did not increase in
      DNA damage. In conclusion, the results supported that AA possesses GABAA receptor
      mediated anxiolytic activity with the lack of myorelaxation and genotoxicity. (c)
      2018 IUBMB Life, 70(5):420-431, 2018.

PMID- 29573148
TI  - Two New Anti-Proliferative C18 -Norditerpenes from the Roots of Podocarpus
      macrophyllus.
AB  - Activity-guided fractionation strategy was used to investigate chemical
      constituents from the roots of Podocarpus macrophyllus. Successfully, two new
      norditerpenes, 2beta-hydroxymakilactone A (1) and 3beta-hydroxymakilactone A (2),
      along with ten known analogues (3 - 12) were isolated. The structures of 1 and 2
      were elucidated by spectroscopic analysis including 1D-, 2D-NMR, and HR-ESI-MS
      data. The previously reported structure of 2,3-dihydro-2alpha-hydroxypodolide was
      revised as 2,3-dihydro-2beta-hydroxypodolide (3) by spectroscopic analysis, and
      was further confirmed by X-ray crystallographic analysis. Cytotoxic activities of
      all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA
      MB-231, HepG-2, and PANC-1) were evaluated. All of them exhibited anti
      proliferative activities (IC50  = 0.3 - 27 MUm), except for 10. Compounds 1, 4,
      5, 6, and 8 exhibited potent inhibitory activities with IC50  < 1 MUm against
      HeLa and AGS cells.

PMID- 29573149
TI  - Freeze-thaw approach: A practical sample preparation strategy for residue
      analysis of multi-class veterinary drugs in chicken muscle.
AB  - Seven drugs from different classes, namely, fluoroquinolones (enrofloxacin,
      ciprofloxacin, sarafloxacin), sulfonamides (sulfadimidine, sulfamonomethoxine),
      and macrolides (tilmicosin, tylosin), were used as test compounds in chickens by
      oral administration, a simple extraction step after cryogenic freezing might
      allow the effective extraction of multi-class veterinary drug residues from
      minced chicken muscles by mix vortexing. On basis of the optimized freeze-thaw
      approach, a convenient, selective, and reproducible liquid chromatography with
      tandem mass spectrometry method was developed. At three spiking levels in blank
      chicken and medicated chicken muscles, average recoveries of the analytes were in
      the range of 71-106 and 63-119%, respectively. All the relative standard
      deviations were <20%. The limits of quantification of analytes were 0.2-5.0 ng/g.
      Regardless of the chicken levels, there were no significant differences (P >
      0.05) in the average contents of almost any of the analytes in medicated chickens
      between this method and specific methods in the literature for the determination
      of specific analytes. Finally, the developed method was successfully extended to
      the monitoring of residues of 55 common veterinary drugs in food animal muscles.

PMID- 29573150
TI  - Determination of oxalate and citrate in urine by capillary electrophoresis using
      solid-phase extraction and capacitively coupled contactless conductivity based on
      an improved mini-cell.
AB  - A new method for the rapid determination of the metabolites oxalate and citrate
      in urine samples was based on capillary electrophoresis and capacitively coupled
      contactless conductivity detection coupled with solid-phase extraction. The
      detection cell for capacitively coupled contactless conductivity detection was
      improved with a smaller inner volume (1.5 nL), reduced noise (0.2~0.5 mV) and
      better reproducibility and durability. Under optimal conditions, oxalate and
      citrate can achieve baseline separation within 4 min and the detection limits
      (S/N = 3) for oxalate and citrate are about 44 and 244 ng/mL, respectively. The
      overall recovery is between 80.0 and 89.2%. This method offers a better choice
      for quantitative analysis of strong anions such as oxalate and citrate in
      diagnostic testing associated with human diseases.

PMID- 29573152
TI  - The benefits of being a near-peer teacher.
AB  - BACKGROUND: Near-peer teaching is used in anatomy education because of its
      benefits to the learner, teacher and faculty members. Despite the range of
      reports focusing on the learner, the advantages for the teacher, which are
      thought to include communication skills, subject knowledge and employability, are
      only beginning to be explored. METHOD: A questionnaire was distributed to the
      teachers involved in anatomy near-peer teaching at the University of Southampton
      and Brighton and Sussex Medical School (BSMS). This questionnaire was designed
      using a rating scale of 0-10 to assess teacher perspectives on their level of
      knowledge, teaching skills and enjoyment of teaching. Free-text responses
      determined the teachers' motivation and perceived benefits from the teaching.
      RESULTS: Twenty-eight questionnaires were gathered (54.9% response rate),
      including 20 from Southampton and eight from BSMS. Long-term knowledge retention
      and better understanding of the material were rated 8.1 and 7.9 out of 10,
      respectively. Eight responses were from currently practising doctors, who rated
      how much they now use their teaching skills as doctors as 8.9 out of 10. Of the
      eight doctors, seven gained points for their foundation programme applications as
      a direct result of near-peer teaching. The most common motivator for engaging in
      teaching was to improve subject matter knowledge and the most common benefit was
      improved communication skills. There are numerous advantages to being a near-peer
      teacher in medical school DISCUSSION: There are numerous advantages to being a
      near-peer teacher in medical school, which include knowledge improvement,
      transferrable professional skills and employability. These initial results
      support the hypothesised benefits to the teachers and provide a foundation for
      further longitudinal studies.

PMID- 29573153
TI  - Cognitive learning theory for clinical teaching.

PMID- 29573151
TI  - More than just sugars: Conserved oligomeric Golgi complex deficiency causes
      glycosylation-independent cellular defects.
AB  - The conserved oligomeric Golgi (COG) complex controls membrane trafficking and
      ensures Golgi homeostasis by orchestrating retrograde vesicle trafficking within
      the Golgi. Human COG defects lead to severe multisystemic diseases known as COG
      congenital disorders of glycosylation (COG-CDG). To gain better understanding of
      COG-CDGs, we compared COG knockout cells with cells deficient to 2 key enzymes,
      Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase and
      uridine diphosphate-glucose 4-epimerase (GALE), which contribute to proper N- and
      O-glycosylation. While all knockout cells share similar defects in glycosylation,
      these defects only account for a small fraction of observed COG knockout
      phenotypes. Glycosylation deficiencies were not associated with the fragmented
      Golgi, abnormal endolysosomes, defective sorting and secretion or delayed
      retrograde trafficking, indicating that these phenotypes are probably not due to
      hypoglycosylation, but to other specific interactions or roles of the COG
      complex. Importantly, these COG deficiency specific phenotypes were also apparent
      in COG7-CDG patient fibroblasts, proving the human disease relevance of our
      CRISPR knockout findings. The knowledge gained from this study has important
      implications, both for understanding the physiological role of COG complex in
      Golgi homeostasis in eukaryotic cells, and for better understanding human
      diseases associated with COG/Golgi impairment.

PMID- 29573155
TI  - Determining discharge destination in geriatric evaluation and management units:
      Is progressive goal attainment a better early indicator of discharge destination
      than improvement in functional independence measure scores?
AB  - AIM: To determine whether progress in goal attainment is a more responsive
      measure of functional improvement than the Functional Independence Measure, and
      whether it is a more accurate predictor of discharge destination in the early
      phase of a Geriatric Evaluation and Management episode. METHODS: The present
      study was a prospective audit of goal achievement, functional ability and
      discharge destination. A total of 83 patients were included in this study.
      Logistic regression was carried out with the outcome variable discharge
      destination (home vs residential care), and the predictors being goal attainment,
      age at admission and change in the Functional Independence Measure motor function
      scale from admission to 2 weeks. RESULTS: Of the predictors, goal attainment was
      the only significant predictor. The overall amount of variability in the
      discharge destination explained by the predictors was 25% (Nagelkerke pseudo R2
      ). CONCLUSIONS: Progressive goal attainment might be a better predictor of
      improvement in function and discharge destination than change in the Functional
      Independence Measure. Geriatr Gerontol Int 2018; 18: 1058-1063.

PMID- 29573154
TI  - The Influence of Dietary Habits and Meat Consumption on Plasma 3-Methylhistidine
      A Potential Marker for Muscle Protein Turnover.
AB  - SCOPE: 3-Methylhistidine (3-MH) as a potential biomarker for muscle protein
      turnover is influenced by meat intake but data on the impact of meat on plasma 3
      MH are scarce. We determined the association of plasma 3-MH, 1-methylhistidine (1
      MH), and creatinine with dietary habits and assessed the impact of a single white
      meat intervention during a meat-free period. METHODS AND RESULTS: Plasma 3-MH, 1
      MH, and creatinine concentrations of healthy young omnivores (n = 19) and
      vegetarians (n = 16) were analyzed together with data on anthropometry, body
      composition, grip strength, and nutrition. After baseline measurements omnivores
      adhered to a meat-free diet for 6 days and received a defined administration of
      chicken breast on day four. At baseline, omnivores had higher plasma 3-MH and 1
      MH concentrations than vegetarians. White meat administration led to a slight
      increase in plasma 3-MH in omnivores. The elevated 3-MH concentrations
      significantly declined within 24 h after white meat intake. CONCLUSION: 1-MH
      concentrations in plasma seem to be suitable to display (white) meat consumption
      and its influence on 3-MH plasma concentration. 3-MH in plasma may be used as a
      biomarker for muscle protein turnover if subjects have not consumed meat in the
      previous 24 h.

PMID- 29573156
TI  - Sevelamer Crystals Found in Necrotic Mucosa of a Perforated Diverticulum.

PMID- 29573157
TI  - Dynamics of influenza in tropical Africa: Temperature, humidity, and co
      circulating (sub)types.
AB  - BACKGROUND: The association of influenza with meteorological variables in
      tropical climates remains controversial. Here, we investigate the impact of
      weather conditions on influenza in the tropics and factors that may contribute to
      this uncertainty. METHODS: We computed the monthly viral positive rate for each
      of the 3 circulating influenza (sub)types (ie, A/H1N1, A/H3N2, and B) among
      patients presenting with influenza-like illness (ILI) or severe acute respiratory
      infections (SARI) in 2 Ugandan cities (Entebbe and Kampala). Using this measure
      as a proxy for influenza activity, we applied regression models to examine the
      impact of temperature, relative humidity, absolute humidity, and precipitation,
      as well as interactions among the 3 influenza viruses on the epidemic dynamics of
      each influenza (sub)type. A full analysis including all 4 weather variables was
      done for Entebbe during 2007-2015, and a partial analysis including only
      temperature and precipitation was done for both cities during 2008-2014. RESULTS:
      For Entebbe, the associations with weather variables differed by influenza
      (sub)type; with adjustment for viral interactions, the models showed that
      precipitation and temperature were negatively correlated with A/H1N1 activity,
      but not for A/H3N2 or B. A mutually negative association between A/H3N2 and B
      activity was identified in both Entebbe and Kampala. CONCLUSION: Our findings
      suggest that key interactions exist among influenza (sub)types at the population
      level in the tropics and that such interactions can modify the association of
      influenza activity with weather variables. Studies of the relationship between
      influenza and weather conditions should therefore determine and account for co
      circulating influenza (sub)types.

PMID- 29573158
TI  - Chemotherapy in patients with unresected pancreatic cancer in Australia: A
      population-based study of uptake and survival.
AB  - AIM: Palliative chemotherapy improves symptom control and prolongs survival in
      patients with unresectable pancreatic cancer, but there is a paucity of data
      describing its use and effectiveness in everyday practice. We explored patterns
      of chemotherapy use in patients with unresected pancreatic cancer in Australia
      and the impact of use on survival. METHODS: We reviewed the medical records of
      residents of New South Wales or Queensland, Australia, diagnosed with
      unresectable pancreatic adenocarcinoma between July 2009 and June 2011.
      Associations between receipt of chemotherapy and sociodemographic, clinical and
      health service factors were evaluated using logistic regression. We used Cox
      proportional hazards models to analyze associations between chemotherapy use and
      survival. RESULTS: Data were collected for 1173 eligible patients. Chemotherapy
      was received by 44% (n = 184/414) of patients with localized pancreatic cancer
      and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended
      on clinical factors, such as performance status and comorbidity burden, and
      nonclinical factors, such as age, place of residence, multidisciplinary team
      review and the type of specialist first encountered. Consultation with an
      oncologist mitigated most of the sociodemographic and service-related disparities
      in chemotherapy use. The receipt of chemotherapy was associated with prolonged
      survival in patients with inoperable pancreatic cancer, including after adjusting
      for common prognostic factors. CONCLUSIONS: These findings highlight the need to
      establish referral pathways to ensure that all patients have the opportunity to
      discuss treatment options with a medical oncologist. This is particularly
      relevant for health care systems covering areas with a geographically dispersed
      population.

PMID- 29573159
TI  - Patients' experiences and preferences for opt-in models and health professional
      involvement in biobanking consent: A cross-sectional survey of Australian cancer
      outpatients.
AB  - BACKGROUND: Many biobanks rely upon patients' willingness to donate biospecimens
      and healthcare professionals to initiate opt-in consent processes. This study
      explored if: (1) patients accept opt-in or opt-out consent models with varying
      levels of professional involvement; (2) professionals discuss participation with
      specific patient groups; and (3) this discussion is associated with patient
      knowledge of biobanking processes. METHODS: Outpatients completed surveys at a
      tertiary cancer center in New South Wales, Australia. Eligible participants were
      English-speaking adults who recently had cancer-related surgery. Participants
      completed 27 questions exploring acceptable consent models, biobanking
      experiences, knowledge, and willingness. Logistic regression and chi-square tests
      examined differences in the characteristics and knowledge of participants who
      were offered the opportunity to participate versus those who were not. RESULTS: A
      total of 113 outpatients participated (97% response). Most participants (92%)
      found opt-out, patient-initiated consent acceptable; however, high acceptability
      was reported for all models except for opt-in, patient-initiated consent (58%).
      University or technical qualifications (P  =  0.001) was associated with
      increased odds (OR = 4.5) of being offered biobanking. The majority did not know
      what occurred to samples after surgery (59.3%) or pathology review (81.4%) and
      ability to answer these questions was associated with discussion of participation
      (P < 0.001). Of the few outpatients who discussed biobanking with their doctor
      (29%), all consented. CONCLUSION: Professional-initiated, opt-in consent resulted
      in a few educated patients being approached; greater professional initiation of
      consent would be fruitful as most patients were willing to participate if asked.
      However, other consent approaches minimizing professional involvement were as
      acceptable to participants warranting further consideration.

PMID- 29573160
TI  - Intraseasonal asynchrony as a factor boosting isolation within a metapopulation:
      The case of the clouded apollo.
AB  - This article discusses the influence of phenology-related intraseasonal
      asynchrony on metapopulation dynamics and stability. As the part played by
      intraseasonal asynchrony is as yet unclear and poorly described, greater account
      of it should be taken in both metapopulation research and conservation practice.
      The subpopulations of the Parnassius mnemosyne metapopulation studied here are
      strongly isolated because of the phenological shift between them, despite the
      relatively small physical distances between them. This isolation is the result of
      a significant temporal shift in the species' flight periods in the main
      metapopulation centers: in some seasons its flight times in the different
      subpopulations did not overlap at all. The predicted results of such strong
      intraseasonal asynchrony are not altogether clear. On the one hand, they reduce
      the vulnerability of the entire metapopulation to the effects of short-term
      random disasters. On the other, the ever-greater isolation of subpopulations may
      cause the metapopulation to become a nonequilibrium one, which will have a
      serious impact on its long-term survival.

PMID- 29573161
TI  - Association between pain control and patient satisfaction outcomes in the
      emergency department setting.
AB  - OBJECTIVE: Pain management and patient satisfaction are key markers for health
      systems performance. There is a lack of consensus on the role of analgesia, its
      adequacy, and its links to patient satisfaction in the ED. The present study
      aimed to assess the relationship between adequacy of analgesia and patient
      satisfaction in the ED setting. METHODS: Consenting adult patients (n = 115)
      presenting to the ED with pain were enrolled, and their pain tracked throughout
      admission with 11 point numerical pain scores. Eleven point numerical scores were
      also utilised to measure satisfaction and compassion at the end of each ED stay.
      The primary outcome was patient satisfaction score >=7. RESULTS: Of 115 enrolled
      patients, 94 (81.7%) were eligible for analysis. Median time to physician
      evaluation was 54.0 min (inter-quartile range [IQR] 35.0-98.0) and median ED
      length of stay was 205 min (IQR 129.0-280.0). Fifty-four patients (57.5%)
      received analgesia during their stay, of whom 36 (38.3%) had a significant
      response to analgesia (>=2 change in pain score). Median time to analgesia was
      87.5 min (IQR 66.1-108.9). Patient satisfaction was inversely associated with
      male sex, and positively correlated (Spearman's rank correlation P < 0.05) with
      increasing age, significant change in pain score (+/-2) and compassion scores.
      CONCLUSION: In the present study of patients presenting to the ED with pain,
      oligoanalgesia remains a significant issue. Male sex was inversely associated
      with satisfaction, whereas compassion, and significant change in pain score were
      associated with improved patient satisfaction. Of the factors analysed, staff
      compassion demonstrated the strongest correlation with satisfaction.

PMID- 29573162
TI  - Changing environment of hyperglycemia in pregnancy: Gestational diabetes and
      diabetes mellitus in pregnancy.
AB  - The diagnosis and treatment of gestational diabetes mellitus (GDM) have been in a
      state of flux since the World Health Organization accepted and endorsed the
      International Diabetes and Pregnancy Study Group's diagnostic pathway and
      criteria in 2013. These new diagnostic criteria identify an increasing number of
      women at risk of hyperglycemia in pregnancy (HGiP). Maternal hyperglycemia
      represents a significant risk to the mother and fetus, in both the short and long
      term. Controversially, metformin use for the treatment of GDM is increasing in
      Australia. This article identifies the multiple and varied presentations of HGiP,
      of which GDM is the most commonly encountered. The degree of maternal
      hyperglycemia experienced affects the outcomes for both the mother and neonate,
      and specific diagnosis determines the appropriate treatment for the pregnancy.
      Given the increasing incidence of women with dysglycemia and those developing
      HGiP, this is an important area for research and clinical attention for all
      health professionals.

PMID- 29573163
TI  - Evaluation of the temporary effect of physical vapor deposition silver coating on
      resistance to infection in transdermal skin and bone integrated pylon with deep
      porosity.
AB  - Periprosthetic infection via skin-implant interface is a leading cause of
      failures and revisions in direct skeletal attachment of limb prostheses. Implants
      with deep porosity fabricated with skin and bone integrated pylons (SBIP)
      technology allow for skin ingrowth through the implant's structure creating
      natural barrier against infection. However, until the skin cells remodel in all
      pores of the implant, additional care is required to prevent from entering
      bacteria to the still nonoccupied pores. Temporary silver coating was evaluated
      in this work as a means to provide protection from infection immediately after
      implantation followed by dissolution of silver layer in few weeks. A sputtering
      coating with 1 um thickness was selected to be sufficient for fighting infection
      until the deep ingrowth of skin in the porous structure of the pylon is
      completed. In vitro study showed less bacterial (Staphylococcus aureus,
      Staphylococcus epidermidis, and Pseudomonas aeruginosa) growth on silver coated
      tablets compared to the control group. Analysis of cellular density of MG-63
      cells, fibroblasts, and mesenchymal stem cells (MSCs) showed that silver coating
      did not inhibit the cell growth on the implants and did not affect cellular
      functional activity. The in vivo study did not show any postoperative
      complications during the 6-month observation period in the model of above-knee
      amputation in rabbits when SBIP implants, either silver-coated or untreated were
      inserted into the bone residuum. Three-phase scintigraphy demonstrated
      angiogenesis in the pores of the pylons. The findings suggest that a silver
      coating with well-chosen specifications can increase the safety of porous
      implants for direct skeletal attachment. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29573165
TI  - A rapid review of serious games: From healthcare education to dental education.
AB  - INTRODUCTION: Games involving technology have the potential to enhance hand-eye
      coordination and decision-making skills. As a result, game characteristics have
      been applied to education and training, where they are known as serious games.
      There is an increase in the volume of literature on serious games in healthcare
      education; however, evidence on their impact is still ambiguous. AIMS: The aims
      of this study were (i) to identify high-quality evidence (systematic reviews or
      meta-analyses) regarding impacts of serious games on healthcare education; and
      (ii) to explore evidence regarding impacts of serious games in dental education.
      METHODS: A rapid review of the literature was undertaken to synthesise available
      evidence and examine serious games in healthcare education (Stage 1) and dental
      education (Stage 2). RESULTS: Nine systematic reviews were included in Stage 1,
      four of which were of high, three of moderate and two of low quality. For Stage
      2, two randomised control trials with moderate quality were included. The
      findings demonstrated that serious games are potentially effective learning tools
      in terms of knowledge and skills improvement, although outcomes of serious games
      over traditional learning approaches were not consistent. In addition, serious
      games appeared to be more engaging and satisfying for students, which could be
      considered as the most important positive impact. CONCLUSION: Serious games
      provide an option for healthcare and dental education but remain underutilised
      and researched. At best, they offer a similar experience to other methods in
      relation to educational outcome; however, they can provide a supplementary
      strategy to engage students and improve learner satisfaction.

PMID- 29573164
TI  - Patient receipt of smoking cessation care in four Australian acute psychiatric
      facilities.
AB  - This study aimed to report the receipt of smoking care, and associated clinical
      and smoking characteristics among smokers admitted to four public psychiatric
      inpatient facilities in New South Wales, Australia. Between October 2012 and July
      2014, adult smokers (N = 236) were surveyed during admission to and 1 month
      following discharge from the facilities. Measures of smoking care receipt were
      reported descriptively, and logistic regression analyses were used to explore
      characteristics associated with care receipt. The majority of participants were
      offered (78%) and used (78%) nicotine replacement therapy (NRT), with 66% of NRT
      users reporting the amount provided was sufficient to reduce cravings. A minority
      of participants (16%) received information or advice to quit smoking, and 60%
      reported smoking throughout their admission. Patients not contemplating quitting
      and those with non-psychotic disorders were more likely to receive an offer of
      NRT. The findings suggest the provision of smoking care in Australian acute
      psychiatric units is sub-optimal overall, with an indication that care may be
      provided selectively to certain patients, rather than systematically to all.
      Development and dissemination of interventions to increase smoking care provision
      in inpatient psychiatry are needed.

PMID- 29573166
TI  - Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with
      type 1 diabetes is common.
AB  - BACKGROUND: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH)
      can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia
      avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts
      clinical outcomes and may be changed by education. AIM: To develop and utilise a
      survey to evaluate patient self-management of overnight glycaemia in adults with
      T1D. METHODS: Adults with T1D attending two Australian tertiary referral diabetes
      clinics completed a survey about their diabetes self-management and glycaemic
      control, including responses to hypothetical pre-bed blood glucose (BG) levels (4
      20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA
      with significance considered at P < 0.05. RESULTS: There were 205 participants
      (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16)
      years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy
      (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of
      BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and
      overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime
      (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants
      reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then
      complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG
      scenarios, with higher rates for CSII users, P = 0.0005. Further education was
      desired by 32% of respondents, with higher rates in those with (44%) versus
      without IHA (25%), P = 0.006. CONCLUSIONS: Many adults with T1D have suboptimal
      knowledge and behaviour regarding overnight BG self-management. A survey, piloted
      herein, may facilitate the identification of patients who could benefit from
      further education.

PMID- 29573167
TI  - Effects of transcranial pulsed electromagnetic field stimulation on quality of
      life in Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Pulsed electromagnetic fields induce a protective and
      anti-inflammatory effect in the nervous system primarily due to growth factor
      upregulation that possibly abates neurodegeneration in Parkinson's disease (PD).
      This study investigated treatment effects of transcranial pulsed electromagnetic
      fields (T-PEMFs) on quality of life in PD and the feasibility and safety of this
      treatment. METHODS: In this double-blinded clinical study, 97 participants with
      idiopathic PD (Hoehn & Yahr stage I-IV), on optimal medical anti-parkinsonian
      treatment, were block randomized (3:3) to either active (n = 49) or placebo
      treatment (n = 48). Treatment with T-PEMFs entailed one daily 30-min home
      treatment for eight consecutive weeks. The 39-item Parkinson's Disease
      Questionnaire (PDQ-39) was assessed at baseline and endpoint. A special
      questionnaire was used to profile adverse events by interviewing the participants
      over the full treatment period. Treatment compliance was accounted for by daily
      treatment registration. RESULTS: The active group improved with respect to
      clinical effect size for the two dimensions, i.e. mobility and activities of
      daily living, compared with the placebo group. No between-group differences were
      found for the remaining PDQ-39 dimensions. There were no between-group difference
      in adverse events. Treatment compliance was 97.9%. CONCLUSION: Treatment with T
      PEMFs improved mobility and activities of daily living scores for clinical effect
      size only in the active group, indicating a positive treatment response for motor
      symptoms. No difference was found between the two groups for the remaining PDQ-39
      dimensions. The treatment had no or only mild adverse events and was performed
      with high compliance.

PMID- 29573168
TI  - Plant G proteins interact with endoplasmic reticulum luminal protein receptors to
      regulate endoplasmic reticulum retrieval.
AB  - Maintaining endoplasmic reticulum (ER) homeostasis is essential for the
      production of biomolecules. ER retrieval, i.e., the retrograde transport of
      compounds from the Golgi to the ER, is one of the pathways that ensures ER
      homeostasis. However, the mechanisms underlying the regulation of ER retrieval in
      plants remain largely unknown. Plant ERD2-like proteins (ERD2s) were recently
      suggested to function as ER luminal protein receptors that mediate ER retrieval.
      Here, we demonstrate that heterotrimeric G protein signaling is involved in ERD2
      mediated ER retrieval. We show that ERD2s interact with the heterotrimeric G
      protein Galpha and Ggamma subunits at the Golgi. Silencing of Galpha, Gbeta, or
      Ggamma increased the retention of ER luminal proteins. Furthermore,
      overexpression of Galpha, Gbeta, or Ggamma caused ER luminal proteins to escape
      from the ER, as did the co-silencing of ERD2a and ERD2b. These results suggest
      that G proteins interact with ER luminal protein receptors to regulate ER
      retrieval.

PMID- 29573169
TI  - Transcriptome-Based Analysis in Lactobacillus plantarum WCFS1 Reveals New
      Insights into Resveratrol Effects at System Level.
AB  - SCOPE: This study was undertaken to expand our insights into the mechanisms
      involved in the tolerance to resveratrol (RSV) that operate at system-level in
      gut microorganisms and advance knowledge on new RSV-responsive gene circuits.
      METHODS AND RESULTS: Whole genome transcriptional profiling was used to
      characterize the molecular response of Lactobacillus plantarum WCFS1 to RSV. DNA
      repair mechanisms were induced by RSV and responses were triggered to decrease
      the load of copper, a metal required for RSV-mediated DNA cleavage, and H2 S, a
      genotoxic gas. To counter the effects of RSV, L. plantarum strongly up- or
      downregulated efflux systems and ABC transporters pointing to transport control
      of RSV across the membrane as a key mechanism for RSV tolerance. L. plantarum
      also downregulated tRNAs, induced chaperones, and reprogrammed its transcriptome
      to tightly control ammonia levels. RSV induced a probiotic effector gene and a
      likely deoxycholate transporter, two functions that improve the host health
      status. CONCLUSION: Our data identify novel protective mechanisms involved in RSV
      tolerance operating at system level in a gut microbe. These insights could
      influence the way RSV is used for a better management of gut microbial ecosystems
      to obtain associated health benefits.

PMID- 29573170
TI  - Control of the Interfacial Wettability to Synthesize Highly Dispersed PtPd
      Nanocrystals for Efficient Oxygen Reduction Reaction.
AB  - Highly dispersed PtPd bimetallic nanocrystals with enhanced catalytic activity
      and stability were prepared by adjusting the interfacial wettability of the
      reaction solution on a commercial carbon support. This approach holds great
      promise for the development of high-performance and low-cost catalysts for
      practical applications.

PMID- 29573171
TI  - Advanced Technologies and Treatments for Diabetes 2018.
AB  - Ann M. Carracher, Payal H. Marathe, 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 Carracher, Marathe, and
      Close review the latest developments relevant to researchers and clinicians.

PMID- 29573172
TI  - Quantification of Urinary Protein Biomarkers of Autosomal Dominant Polycystic
      Kidney Disease by Parallel Reaction Monitoring.
AB  - PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a life-long
      disease in which the genes responsible are known, but the pathogenesis of cyst
      formation and cyst growth are not understood. Cyst growth ultimately leads to end
      stage renal failure in most patients. Analysis of the urinary proteome offers the
      potential to identify proteins that indicate the presence of cysts (and thus
      provides diagnosis) as well as the rates of cyst growth (providing prognostic
      information). EXPERIMENTAL DESIGN: A scheduled parallel reaction monitoring
      (sPRM) assay is performed on urine samples from 14 patients and 18 normal
      controls. For relative quantification, stable isotope-labeled synthetic peptides
      are spiked in the urinary protein digests prior to data collection. The data are
      subsequently normalized to creatinine and protein concentration in the respective
      urine samples to control for variations in water intake between individuals.
      RESULTS: Out of the 143 urinary proteins targeted for sPRM assay, 69 proteins are
      observed to be significantly dysregulated in ADPKD. The dysregulated proteins are
      used to cluster ADPKD patients into those who are more or less similar to normal
      controls. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that sPRM is a
      promising approach to rapidly screen large numbers of proteins in urine in order
      to provide earlier diagnosis and potentially better understand the pathogenesis
      of ADPKD development and progression.

PMID- 29573173
TI  - Chinese consensus on chronic gastritis (2017, Shanghai).

PMID- 29573174
TI  - Assessing hyperthermia-induced vasodilation in human skin in vivo using
      optoacoustic mesoscopy.
AB  - The aim of this study was to explore the unique imaging abilities of optoacoustic
      mesoscopy to visualize skin structures and microvasculature with the view of
      establishing a robust approach for monitoring heat-induced hyperemia in human
      skin in vivo. Using raster-scan optoacoustic mesoscopy (RSOM), we investigated
      whether optoacoustic (photoacoustic) mesoscopy can identify changes in skin
      response to local heating at microvasculature resolution in a cross-sectional
      fashion through skin in the human forearm. We visualized the heat-induced
      hyperemia for the first time with single-vessel resolution throughout the whole
      skin depth. We quantified changes in total blood volume in the skin and their
      correlation with local heating. In response to local heating, total blood volume
      increased 1.83- and 1.76-fold, respectively, in the volar and dorsal aspects of
      forearm skin. We demonstrate RSOM imaging of the dilation of individual vessels
      in the skin microvasculature, consistent with hyperemic response to heating at
      the skin surface. Our results demonstrate great potential of RSOM for elucidating
      the morphology, functional state and reactivity of dermal microvasculature, with
      implications for diagnostics and disease monitoring. Image: Cross-sectional view
      of skin microvasculature dilated in response to hyperthermia.

PMID- 29573175
TI  - One anastomosis gastric bypass versus Roux-en-Y gastric bypass for morbid
      obesity: a meta-analysis.
AB  - We aim to review the available literature on morbidly obese patients treated with
      one anastomosis gastric bypass (OAGB) or Roux-en-Y gastric bypass (RYGB) in order
      to compare the clinical outcomes of the two methods. A literature search was
      performed in PubMed, Cochrane library and Scopus, in accordance with the PRISMA
      guidelines. Twelve studies met the inclusion criteria (7452 patients). OAGB was
      associated with shorter mean operative time. The length of hospital stay was
      comparable between the two procedures. The incidence of leaks, marginal ulcer,
      dumping, bowel obstruction, revisions and mortality was similar between the two
      approaches. The incidence of malnutrition was increased in patients treated with
      OAGB, while the incidence of internal hernia and bowel obstruction was greater in
      the RYGB group. In addition, the percentage excess weight loss at 1, 2 and 5
      years post-operatively was greater for the OAGB group. The rate of type 2
      diabetes remission was greater in the OAGB group. The rate of hypertension and
      dyslipidemia remission was also similar between OAGB and RYGB. Randomized
      controlled trials, comparing RYGB to OAGB, are necessary to further assess their
      clinical outcomes.

PMID- 29573176
TI  - Thunderstorm Asthma - Revealing a hidden at-risk population.
AB  - BACKGROUND & AIM: To characterise the nature and extent of respiratory symptoms
      in healthcare workers during the Melbourne Thunderstorm Asthma event. METHODS: A
      survey was conducted among staff and volunteers across Eastern Health,
      distributed on the intranet homepage, by e-mail, and by word of mouth. Anonymous
      survey questions were constructed to assess prior and current diagnoses of
      relevance, symptoms, and demography. RESULTS: There were 515 participants (80%
      female, n=411) who completed the survey of approximately 9000 potential
      respondents (~6% response rate). 132 (25.6%) had symptoms suggestive of asthma
      during the ETSA event, the majority of which did not seek professional medical
      help. Notably, of those with ETSA-like symptoms, only 58 (43.9%) had a history of
      asthma while 97 (73.5%) had a history of allergic rhinitis. Specifically, a
      history of allergic rhinitis (OR 2.77, p < 0.001), a history of asthma (OR 1.67,
      p = 0.037), and being of self-identified Asian ethnicity (OR 3.24, p < 0.001)
      were all strong predictors of ETSA-like symptoms. Being predominantly indoors was
      not protective. CONCLUSIONS: Our study provides evidence for the presence of a
      large cohort of sufferers during the Melbourne Thunderstorm Asthma event of 2016
      that did not come to the attention of medical services, implying a potentially
      hidden and significant susceptible population. Further research should help
      clarify the true prevalence of vulnerability in the general population, with
      important public health implications.

PMID- 29573177
TI  - A four-season longitudinal study of enterohaemorrhagic Escherichia coli in beef
      cow-calf herds in Mississippi and Nebraska.
AB  - Our objective was to describe the probability of detecting seven serogroups of
      enterohaemorrhagic Escherichia coli (EHEC-7) of public health importance in
      faecal samples from beef cow-calf herds and to test for factors associated with
      their detection. Fresh faecal samples (n = 85) from two Mississippi and two
      Nebraska herds were collected in each of four seasons. Samples were tested for
      each EHEC-7 serogroup by a molecular screening assay. Separate management groups
      within herds were sampled, and group-level factors were recorded. To measure the
      effects of factors on faecal shedding of EHEC-7, separate multivariable logistic
      regression models were used, accounting for the random effect of clustering by
      group within farm. Statistical significance was set alpha = 0.05. Fifty-nine
      samples (4.3%) were positive for EHEC O26, and Nebraska samples were more likely
      to be positive than Mississippi samples (OR = 12.4, 95% CI: 1.1, 139.2). Forty
      four samples (3.2%) were positive for EHEC O45. Odds for detection were greater
      in the summer than all other seasons combined (OR = 4.2, 95% CI: 1.3, 14.0), and
      odds decreased if a precipitation event occurred (OR = 0.07, 95% CI: 0.006, 0.8).
      EHEC O103 was detected in 66 samples (4.9%) with increased probability to be
      detected at increased temperature. EHEC O111 was detected in 71 samples (5.2%),
      and 43 samples (3.2%) were positive for EHEC O145. Both EHEC O111 and O145 were
      associated separately with season, with greater probability for detection in the
      summer. Eighteen (1.3%) and 68 (5.0%) samples were positive for EHEC O121 and
      EHEC O157, respectively. We failed to detect significant explanatory factors
      associated with probability to detect EHEC O121 or O157. Factors that vary by
      time and place, such as precipitation, ambient temperature, region and season,
      are uniquely associated with the probability to detect EHEC-7 in fresh faeces
      collected from cow-calf herds.

PMID- 29573178
TI  - On the role of interference in laser-based mid-infrared widefield
      microspectroscopy.
AB  - A laser's high degree of coherence leads to interferences, which-in the absence
      of precautions-can cause severe image distortions such as fringes and speckles
      and which thereby strongly hamper a meaningful interpretation of hyperspectral
      images in laser-based widefield microspectroscopy. While images and spectra of
      homogenous samples may already suffer from interferences, any structured object
      such as a tissue thin section will add to these distortions due to wavelength-
      and, in particular, sample-dependent phase shifts (structure sizes, absorption
      coefficients, refractive indices). This effect is devastating for the universal
      applicability of laser-based microspectroscopy especially in the mid-infrared
      (MIR), where cell sizes are of the same dimension as the wavelength of the
      illumination source. Here, we show that the impact of interferences is strongly
      mitigated by reducing the time-averaged spatiotemporal coherence properties of
      the illumination using a moving plus a stationary scatterer. In this case, the
      illumination path provides a pseudothermal radiation source and spatially
      resolved spectra can be obtained at the quality of the reference method, that is,
      Fourier-transform infrared microspectroscopy, without compromising spectral or
      spatial resolution.

PMID- 29573179
TI  - Towards robot-assisted anchor deployment in beating-heart mitral valve surgery.
AB  - BACKGROUND: Beating-heart intracardiac surgery promises significant benefits for
      patients compared with cardiopulmonary bypass based procedures. However, the fast
      motions of the heart introduce serious challenges for surgeons. METHODS: In this
      work, a new impedance-controlled master-slave telerobotic system is developed to
      help perform anchor deployment for mitral valve annuloplasty under the guidance
      of live ultrasound images of the heart. The proposed bilateral teleoperation
      system can both reflect the non-oscillatory portion of slave-heart tissue
      interaction force on the surgeon's hand as haptic feedback and implement rapid
      compensation for the beating heart's motion. The surgical task involves
      performing anchor deployment on a simulated moving heart tissue to evaluate the
      effectiveness of the proposed strategy for safely interacting with a moving
      organ. RESULTS AND CONCLUSIONS: The results obtained show that the telerobotic
      system increases the success rate of anchor deployment by 100% and reduces the
      excess force application rate by 70% compared with manual attempts.

PMID- 29573180
TI  - A comparison of methods for meta-analysis of a small number of studies with
      binary outcomes.
AB  - Meta-analyses often include only a small number of studies (<=5). Estimating
      between-study heterogeneity is difficult in this situation. An inaccurate
      estimation of heterogeneity can result in biased effect estimates and too narrow
      confidence intervals. The beta-binominal model has shown good statistical
      properties for meta-analysis of sparse data. We compare the beta-binominal model
      with different inverse variance random (eg, DerSimonian-Laird, modified Hartung
      Knapp, and Paule-Mandel) and fixed effects methods (Mantel-Haenszel and Peto) in
      a simulation study. The underlying true parameters were obtained from empirical
      data of actually performed meta-analyses to best mirror real-life situations. We
      show that valid methods for meta-analysis of a small number of studies are
      available. In fixed effects situations, the Mantel-Haenszel and Peto methods
      performed best. In random effects situations, the beta-binominal model performed
      best for meta-analysis of few studies considering the balance between coverage
      probability and power. We recommended the beta-binominal model for practical
      application. If very strong evidence is needed, using the Paule-Mandel
      heterogeneity variance estimator combined with modified Hartung-Knapp confidence
      intervals might be useful to confirm the results. Notable most inverse variance
      random effects models showed unsatisfactory statistical properties also if more
      studies (10-50) were included in the meta-analysis.

PMID- 29573181
TI  - Recent Advances in Imidazoliumyl-Substituted Phosphorus Compounds.
AB  - This review aims to highlight the recent developments in the chemistry of
      selected imidazoliumyl-substituted phosphorus compounds. The synthetic approaches
      for their preparation with phosphorus in various oxidation states and
      coordination environments are discussed. Their intriguing properties and
      versatile chemistry strongly depends on the bonding motif at the P atoms, which
      is given special focus.

PMID- 29573182
TI  - Variations of pulmonary vein drainage critical for lung resection assessed by
      three-dimensional computed tomography angiography.
AB  - BACKGROUND: It is important to understand pulmonary vein drainage pattern
      variations and their frequency in order to perform safe anatomical pulmonary
      resection. METHODS: Variations and frequencies were assessed using three
      dimensional computed tomography angiography (3D-CT) in 194 patients. In cases
      where the tumor or lymph node caused atelectasis or compression of hilar
      structures, the involved lobes were excluded from the analyses. RESULTS: We
      confirmed variant drainage patterns in 15/189 (8.0%) patients in the right upper
      lobe (RUL), 29/189 (15.3%) in the right middle lobe (RML), 18/192 (9.5%) in the
      right lower lobe (RLL), and 5/187 (2.6%) in the left upper lobe (LUL). There was
      no variant type in the left lower lobe (LLL). There were 14 (7.4%) cases of
      anomalous superior posterior pulmonary vein of RUL (V2 ) drainage: V2 draining to
      the superior pulmonary vein (SPV) (n = 2, 1.1%), V2 to the inferior pulmonary
      vein (IPV) (n = 7, 3.7%), V2 to the left atrium (LA) (n = 2, 1.1%), and V6 to the
      apical pulmonary vein of the RLL (n = 3, 1.6%). There was a posterior pulmonary
      vein, V3 to RML pulmonary vein in one case (0.5%). The RML pulmonary vein drained
      into the IPV in 14 (7.4%) and into the LA in 15 (7.9%) cases. The right V6
      directly drained into the LA in 15 (7.9%) and V6 into the SPV in 3 (1.6%) cases.
      The lingular pulmonary vein drained into the IPV in one case (0.5%) and into the
      LA in two cases (1.1%). The inferior lingular pulmonary vein V5 drained into the
      IPV and into the LA in one case (0.5%), respectively. CONCLUSION: We describe
      anomalous pulmonary venous drainage patterns and their frequencies particular to
      anatomic surgical resection. 3D-CT is useful to find such variations.

PMID- 29573183
TI  - Label-free quantitative chemical imaging and classification analysis of
      adipogenesis using mouse embryonic stem cells.
AB  - Stem cells have received much attention recently for their potential utility in
      regenerative medicine. The identification of their differentiated progeny often
      requires complex staining procedures, and is challenging for intermediary stages
      which are a priori unknown. In this work, the ability of label-free quantitative
      coherent anti-Stokes Raman scattering (CARS) micro-spectroscopy to identify
      populations of intermediate cell states during the differentiation of murine
      embryonic stem cells into adipocytes is assessed. Cells were imaged at different
      days of differentiation by hyperspectral CARS, and images were analysed with an
      unsupervised factorization algorithm providing Raman-like spectra and spatially
      resolved maps of chemical components. Chemical decomposition combined with a
      statistical analysis of their spatial distributions provided a set of parameters
      that were used for classification analysis. The first 2 principal components of
      these parameters indicated 3 main groups, attributed to undifferentiated cells,
      cells differentiated into committed white pre-adipocytes, and differentiating
      cells exhibiting a distinct protein globular structure with adjacent lipid
      droplets. An unsupervised classification methodology was developed, separating
      undifferentiated cell from cells in other stages, using a novel method to
      estimate the optimal number of clusters. The proposed unsupervised classification
      pipeline of hyperspectral CARS data offers a promising new tool for automated
      cell sorting in lineage analysis.

PMID- 29573184
TI  - Batch effects in a multiyear sequencing study: False biological trends due to
      changes in read lengths.
AB  - High-throughput sequencing is a powerful tool, but suffers biases and errors that
      must be accounted for to prevent false biological conclusions. Such errors
      include batch effects; technical errors only present in subsets of data due to
      procedural changes within a study. If overlooked and multiple batches of data are
      combined, spurious biological signals can arise, particularly if batches of data
      are correlated with biological variables. Batch effects can be minimized through
      randomization of sample groups across batches. However, in long-term or multiyear
      studies where data are added incrementally, full randomization is impossible, and
      batch effects may be a common feature. Here, we present a case study where false
      signals of selection were detected due to a batch effect in a multiyear study of
      Alpine ibex (Capra ibex). The batch effect arose because sequencing read length
      changed over the course of the project and populations were added incrementally
      to the study, resulting in nonrandom distributions of populations across read
      lengths. The differences in read length caused small misalignments in a subset of
      the data, leading to false variant alleles and thus false SNPs. Pronounced allele
      frequency differences between populations arose at these SNPs because of the
      correlation between read length and population. This created highly statistically
      significant, but biologically spurious, signals of selection and false
      associations between allele frequencies and the environment. We highlight the
      risk of batch effects and discuss strategies to reduce the impacts of batch
      effects in multiyear high-throughput sequencing studies.

PMID- 29573185
TI  - Epigastric hernia contiguous with the laparoscopic port site after endoscopic
      robotic total prostatectomy.
AB  - Both laparoscopic and endoscopic robotic surgery are widely accepted for many
      abdominal surgeries. However, the port site for the laparoscope cannot be easily
      sutured without defect, particularly in the cranial end; this can result in a
      port-site incisional hernia and trigger the progressive thinning and stretching
      of the linea alba, leading to epigastric hernia. In the present case, we
      encountered an epigastric hernia contiguous with an incisional scar at the port
      site from a previous endoscopic robotic total prostatectomy. Abdominal ultrasound
      and CT revealed that the width of the linea alba was 30-48 mm. Previous CT images
      prepared before endoscopic robotic prostatectomy had shown a thinning of the
      linea alba. We should be aware of the possibility of epigastric hernia after
      laparoscopic and endoscopic robotic surgery. In laparoscopic and endoscopic
      robotic surgery for a high-risk patient for epigastric hernia, we should consider
      additional sutures cranial to the port-site incision to prevent of an epigastric
      hernia.

PMID- 29573186
TI  - A high-density SNP chip for genotyping great tit (Parus major) populations and
      its application to studying the genetic architecture of exploration behaviour.
AB  - High-density SNP microarrays ("SNP chips") are a rapid, accurate and efficient
      method for genotyping several hundred thousand polymorphisms in large numbers of
      individuals. While SNP chips are routinely used in human genetics and in animal
      and plant breeding, they are less widely used in evolutionary and ecological
      research. In this article, we describe the development and application of a high
      density Affymetrix Axiom chip with around 500,000 SNPs, designed to perform
      genomics studies of great tit (Parus major) populations. We demonstrate that the
      per-SNP genotype error rate is well below 1% and that the chip can also be used
      to identify structural or copy number variation. The chip is used to explore the
      genetic architecture of exploration behaviour (EB), a personality trait that has
      been widely studied in great tits and other species. No SNPs reached genomewide
      significance, including at DRD4, a candidate gene. However, EB is heritable and
      appears to have a polygenic architecture. Researchers developing similar SNP
      chips may note: (i) SNPs previously typed on alternative platforms are more
      likely to be converted to working assays; (ii) detecting SNPs by more than one
      pipeline, and in independent data sets, ensures a high proportion of working
      assays; (iii) allele frequency ascertainment bias is minimized by performing SNP
      discovery in individuals from multiple populations; and (iv) samples with the
      lowest call rates tend to also have the greatest genotyping error rates.

PMID- 29573187
TI  - Propensity-Matched Analysis of Patients with Mixed Hepatocellular
      Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation.
AB  - Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both
      hepatocellular and biliary differentiation. While liver transplantation (LT) is
      the gold standard treatment for patients with unresectable hepatocellular
      carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of
      poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC
      CCA and a matched cohort of HCC LT recipients. A retrospective, single-center
      analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched
      1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha
      fetoprotein) and explant (pathologic diameter, grade/differentiation, and
      vascular invasion) tumor characteristics. Compared with HCC patients matched on
      pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade,
      more poorly differentiated tumors, but similar T stage and vascular invasion. HCC
      CCA recipients trended toward inferior recurrence-free survival at 5 years (28%
      versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to
      recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P =
      0.07). However, when matched to a separate HCC cohort with similar explant
      pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P
      = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA
      recurrences occurred with poorly differentiated tumors (median survival 21.3
      months), without a single recurrence in 5 of the 12 HCC-CCA patients with well
      moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA
      tumors are more likely poorly differentiated tumors compared with HCC with
      similar pretransplant characteristics. However, compared with HCC with similar
      pathologic characteristics, they display similar recurrence-free survival and are
      not inherently more aggressive tumors. Low-grade, well-moderately differentiated
      HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they
      should not be excluded from LT. Improved pretransplant identification of
      pathologic characteristics in HCC-CCA may allow for successful utilization of LT
      in this subset of patients.

PMID- 29573188
TI  - Cooperative and FRET-Assisted Brightness Enhancement in Oligo(phenylene
      ethynylene): Quantum Dot Organic-Inorganic Nanohybrids.
AB  - Herein, we combine the ideas of concerted emission from fluorophore ensembles and
      its further amplification through FRET in an organic-inorganic hybrid approach.
      Spherical and highly fluorescent organic nanoparticles (FONPs, Phif =0.38),
      prepared by the self-assembly of oligo(phenylene ethynylene) (OPE) molecules,
      were selected as a potential donor material. This organic core was then decorated
      with a shell of fluorescent CdSe/ZnS core-shell quantum dots (QDs; <d>?5.5 nm,
      Phif =0.27) with the aid of a bifunctional ligand, mercaptopropionic acid. Its
      high extinction coefficient (epsilon~4.1*105  m-1  cm-1 ) and good spectral match
      with the emission of the FONPs (J(lambda)~4.08*1016  m-1  cm-1  nm4 ) made them a
      better acceptor candidate to constitute an efficient FRET pair (PhiFRET =0.8). As
      a result, the QD fluorescence intensity was enhanced by more than twofold. The
      fundamental calculations carried out indicated an improvement in all the FRET
      parameters as the number of QDs around the FONPs was increased. This, together
      with the localization of multiple QDs in a nanometric dimension (volume~1.8*106 
      nm3 ), gave highly bright reddish luminescent hybrid particles as visualized
      under a fluorescence microscope.

PMID- 29573189
TI  - Assessment of physical activity intensity and duration in the paediatric
      population: evidence to support an a priori hypothesis and sample size in the
      agreement between subjective and objective methods.
AB  - We aimed to provide evidence for an a priori hypothesis and sample size for
      subjectively assessing physical activity intensity and duration in paediatric
      population, adopting objective methods as the reference. We searched electronic
      databases, reference lists and author databases. Correlation coefficients were
      pooled as an indicator of agreement estimates. We found 183 agreement analyses
      (94.5% based on correlation coefficients) from 89 studies that met our inclusion
      criteria. We identified four physical activity parameters addressing intensity
      and two parameters addressing duration. The physical activity parameters focusing
      on intensity were measured only by questionnaires, and the best correlation was
      achieved by moderate-to-vigorous physical activity compared with a heart rate
      monitor. In addition, total physical activity duration had a stronger correlation
      with an accelerometer when measured by diaries or logs than when measured by
      questionnaires. In both cases, the correlation was moderate. Studies with sample
      sizes between 50 and 99 subjects showed measurements that were stable in both
      magnitude and interpretation. Our findings suggest that the agreement between
      subjective and objective methods for assessing physical activity intensity and
      duration is weak to moderate. Furthermore, sample sizes ranging from 50 to 99
      subjects provide stable agreement estimates between methods.

PMID- 29573190
TI  - Infective endocarditis: a Hunter New England perspective.
AB  - BACKGROUND: Infective endocarditis (IE) is a severe infection conferring
      significant morbidity and mortality. It is associated with geographical
      variation, complicating diagnosis and treatment of patients in a standardised
      manner. AIM: To evaluate the presentation, treatment and outcomes of patients
      with IE in the Hunter New England Local Health District (HNELHD). METHODS: A
      total of 112 patients with definite IE admitted to hospitals within the HNELHD
      between 2011 and 2015 was retrospectively analysed. RESULTS: The mean age of
      patients was 56.8 (standard deviation 20.3) and 62.5% were male. The most common
      valve affected was the mitral valve, in 41% of patients, and the most common
      organism was Staphylococcus aureus, in 47.7% of patients. A history of IE was
      present in 10% of patients and 19.6% presented with prosthetic valve IE. Survival
      among patients treated surgically was 100% at 30 days, 92% at 1 year and 83% at 3
      years, versus 82% at 30 days, 65% at 1 year and 51% at 3 years for those not
      operated (P = 0.004). Valve type, organism and Australian Standard Geographical
      Classification remoteness area did not have a statistically significant effect on
      mortality (P-value 0.095, 0.456 and 0.186, respectively). Factors associated with
      improved survival by univariate analysis included surgery and multidisciplinary
      team review. CONCLUSION: IE in the HNELHD affects a relatively young cohort of
      patients and is associated with a high mortality. Outcomes could be improved by
      implementation of a multidisciplinary team approach and inpatient cardiac
      surgery.

PMID- 29573191
TI  - Is fascial defect closure with intraperitoneal onlay mesh superior to standard
      intraperitoneal onlay mesh for laparoscopic repair of large incisional hernia?
AB  - INTRODUCTION: The ideal surgical technique for large incisional hernia repair has
      not yet been identified. The aim of this study was to evaluate surgical outcomes
      of standard intraperitoneal onlay mesh (sIPOM) versus fascial defect closure with
      intraperitoneal onlay mesh (IPOM-Plus) for large incisional hernia repair.
      METHODS: Of 49 patients who underwent laparoscopic incisional hernia repair
      between November 2005 and December 2016, 26 cases with large incisional hernia
      (transverse diameter >=10 cm) were examined to compare surgical outcomes between
      sIPOM (n = 12) and IPOM-Plus (n = 14). Statistical analysis was performed using
      the Mann-Whitney U-test and Fisher's exact test. P < 0.05 was considered to be
      statistically significant. RESULTS: We compared sIPOM with IPOM-Plus for similar
      hernia types during median follow-up periods of 53 and 21 months, respectively.
      The operation time was 150 min for sIPOM and 148 min for IPOM-Plus (P = 0.6220).
      Early postoperative complications including seroma formation were observed in
      four sIPOM patients (33%) and three IPOM-Plus patients (21%) (P = 0.6652).
      Significantly more mesh bulged with sIPOM than with IPOM-Plus (50% vs 0%; P =
      0.0082). Chronic pain lasting 3 months after the operation was found in two cases
      of IPOM-Plus (14%), but this was not statistically significant. Postoperative
      hospital stay was longer for sIPOM patients than for IPOM-Plus patients. Only one
      recurrence was observed in the sIPOM group (8%), but this was not statistically
      significant. CONCLUSION: For large incisional hernia repair, IPOM-Plus seems to
      be more effective than sIPOM in terms of reducing mesh bulging.

PMID- 29573192
TI  - Responses of fungal community composition to long-term chemical and organic
      fertilization strategies in Chinese Mollisols.
AB  - How fungi respond to long-term fertilization in Chinese Mollisols as sensitive
      indicators of soil fertility has received limited attention. To broaden our
      knowledge, we used high-throughput pyrosequencing and quantitative PCR to explore
      the response of soil fungal community to long-term chemical and organic
      fertilization strategies. Soils were collected in a 35-year field experiment with
      four treatments: no fertilizer, chemical phosphorus, and potassium fertilizer
      (PK), chemical phosphorus, potassium, and nitrogen fertilizer (NPK), and chemical
      phosphorus and potassium fertilizer plus manure (MPK). All fertilization
      differently changed soil properties and fungal community. The MPK application
      benefited soil acidification alleviation and organic matter accumulation, as well
      as soybean yield. Moreover, the community richness indices (Chao1 and ACE) were
      higher under the MPK regimes, indicating the resilience of microbial diversity
      and stability. With regards to fungal community composition, the phylum
      Ascomycota was dominant in all samples, followed by Zygomycota, Basidiomycota,
      Chytridiomycota, and Glomeromycota. At each taxonomic level, the community
      composition dramatically differed under different fertilization strategies,
      leading to different soil quality. The NPK application caused a loss of
      Leotiomycetes but an increase in Eurotiomycetes, which might reduce the plant
      fungal symbioses and increase nitrogen losses and greenhouse gas emissions.
      According to the linear discriminant analysis (LDA) coupled with effect size (LDA
      score > 3.0), the NPK application significantly increased the abundances of
      fungal taxa with known pathogenic traits, such as order Chaetothyriales, family
      Chaetothyriaceae and Pleosporaceae, and genera Corynespora, Bipolaris, and
      Cyphellophora. In contrast, these fungi were detected at low levels under the MPK
      regime. Soil organic matter and pH were the two most important contributors to
      fungal community composition.

PMID- 29573193
TI  - Importance of the site of positive surgical margin in salvage external beam
      radiation therapy for biochemical recurrence of prostate cancer after radical
      prostatectomy.
AB  - The aim of this study was to examine long-term outcomes in patients who received
      salvage radiotherapy (SRT) for biochemical recurrence (BRec) of prostate cancer
      after radical prostatectomy (RP). One hundred and twenty patients with prostate
      cancer who underwent SRT for BRec after RP without evidence of clinical disease
      were identified in our institution from 2002 to 2014. Prescription doses to
      prostate beds were 64.8 Gy with a fractional dose of 1.8 Gy in 96.7% of the
      patients. In three-dimensional conformal radiation therapy (3D-CRT), the seminal
      vesicle bed (SVB) was not included in the radiation fields. The prognostic
      factors for BRec-free survival (BRFS) and incidence of acute and late toxicities
      were investigated. Median follow-up duration after SRT was 64.9 months. The 5
      year rates of BRFS, overall survival (OS), cause-specific survival (CSS), and
      clinical recurrence-free survival (CRFS) were 39.2%, 98.3%, 97.0%, and 91.9%,
      respectively. Only two patients experienced late grade 3 toxicity of hematuria.
      Multivariate analysis revealed that BRFS was significantly favorable in patients
      with prostate-specific antigen (PSA) values <0.5 ng/mL at the initiation of SRT
      and pathological Gleason score not including Gleason grade 5. In patients treated
      with 3D-CRT, a positive surgical margin at the base of the prostate influenced
      BRFS unfavorably in comparison with positive surgical margins at other sites. SRT
      for patients with BRec after RP was performed very safely in our institution.
      However, to improve BRFS, adequate inclusion of the SVB appears mandatory,
      especially in cases of positive surgical margins at the base of the prostate.

PMID- 29573194
TI  - Long-term outcomes in patients with nasopharyngeal carcinoma treated with reduced
      volume conformal radiotherapy: A retrospective cohort study.
AB  - INTRODUCTION: While the optimal target volumes for primary nasopharyngeal tumour
      are still subject to debate, we evaluated primary tumour volumes in
      nasopharyngeal carcinoma (NPC) patients treated according to an institutional
      protocol with a reduced volume approach and compared them to those determined by
      Radiation Therapy Oncology Group (RTOG)-0615 guidelines. METHODS: This single
      centre retrospective analysis included 36 NPC patients treated between 2/2007 and
      3/2014. Planning target volume (PTV)-P 50 (50 Gy isodose to the primary tumour)
      included the gross tumour and the entire nasopharyngeal mucosa (clinical target
      volume [CTV]-P 50) with 5 mm margins. The PTV-P 50 volumes, as determined by our
      protocol, were compared to those obtained with RTOG-0615 PTV-P 59.4 (59.4 Gy to
      the primary tumour). Clinical outcomes were also analysed. RESULTS: Median
      (range) follow-up: 48 (21-108) months; 88.9% were males; median age was 53 (27
      86) years; 14%, 53%, and 33% had stage II, III, and IV disease at diagnosis,
      respectively. Median volume of PTV-P 50: 209.0 (92.6-568.0) cc. Median volume of
      RTOG-0615 PTV-P 59.4-P: 292.0 (123.6-425.1) cc. The PTV-P volume was
      significantly smaller than that delineated according to the RTOG-0615 protocol (p
      < 0.001). Isolated local relapse as first site of recurrence occurred in five
      patients: two with stage III, two with IVA and one with IVB disease; all had
      advanced local disease at diagnosis. All local recurrences occurred in the PTV-P
      69-70 region. CONCLUSION: A reduced volume approach for radiotherapy in primary
      NPC provided acceptable long-term local control.

PMID- 29573195
TI  - Spindle assembly in egg extracts of the Marsabit clawed frog, Xenopus borealis.
AB  - Egg extracts of the African clawed frog Xenopus laevis have provided a cell-free
      system instrumental in elucidating events of the cell cycle, including mechanisms
      of spindle assembly. Comparison with extracts from the diploid Western clawed
      frog, Xenopus tropicalis, which is smaller at the organism, cellular and
      subcellular levels, has enabled the identification of spindle size scaling
      factors. We set out to characterize the Marsabit clawed frog, Xenopus borealis,
      which is intermediate in size between the two species, but more recently diverged
      in evolution from X. laevis than X. tropicalis. X. borealis eggs were slightly
      smaller than those of X. laevis, and slightly smaller spindles were assembled in
      egg extracts. Interestingly, microtubule distribution across the length of the X.
      borealis spindles differed from both X. laevis and X. tropicalis. Extract mixing
      experiments revealed common scaling phenomena among Xenopus species, while
      characterization of spindle factors katanin, TPX2, and Ran indicate that X.
      borealis spindles possess both X. laevis and X. tropicalis features. Thus, X.
      borealis egg extract provides a third in vitro system to investigate interspecies
      scaling and spindle morphometric variation.

PMID- 29573196
TI  - Efatutazone and T0901317 exert synergistically therapeutic effects in acquired
      gefitinib-resistant lung adenocarcinoma cells.
AB  - The development of acquired EGFR-TKI therapeutic resistance is still a serious
      clinical problem in the management of lung adenocarcinoma. Peroxisome
      proliferator activated receptor gamma (PPARgamma) agonists may exhibit anti-tumor
      activity by transactivating genes which are closely associated with cell
      proliferation, apoptosis, and differentiation. However, it remains not clear
      whether efatutazone has similar roles in lung adenocarcinoma cells of gefitinib
      resistant such as HCC827-GR and PC9-GR. It has been demonstrated by us that
      efatutazone prominently increased the mRNA and protein expression of PPARgamma,
      liver X receptor alpha (LXRalpha),as well as ATP binding cassette subfamily A
      member 1 (ABCA1). In the presence of GW9662 (a specific antagonist of PPARgamma)
      or GGPP (a specific antagonist of LXRalpha), efatutazone (40 MUmol/L) restored
      the proliferation of both HCC827-GR and PC9-GR cells and obviously inhibited the
      increased protein and mRNA expression of PPAR-gamma, LXR-alpha, and ABCA1 induced
      by efatutazone. LXRalpha knockdown by siRNA (si-LXRalpha) significantly promoted
      the HCC827-GR and PC9-GR cells proliferation, whereas incubation efatutazone with
      si-LXRalpha restored the proliferation ability compared with the control group.
      In addition, combination of efatutazone and LXRalpha agonist T0901317 showed a
      synergistic therapeutic effect on lung adenocarcinoma cell proliferation and PPAR
      gamma, LXR A and ABCA1 protein expression. These results indicate that
      efatutazone could inhibit the cells proliferation of HCC827-GR and PC9-GR through
      PPARgamma/LXRalpha/ABCA1 pathway, and synergistic therapeutic effect is achieved
      when combined with T0901317.

PMID- 29573197
TI  - Describing symptoms using the Symptom Screening in Pediatrics Tool in
      hospitalized children with cancer and hematopoietic stem cell transplant
      recipients.
AB  - Objectives were to describe any bothersome symptom and severely bothersome
      symptoms in inpatient children with cancer and hematopoietic stem cell transplant
      (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT
      recipients who were receiving active treatment for cancer, admitted to hospital,
      and expected to be in hospital 3 days later. We administered the self-report
      Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified
      any degree of symptom bother (at least "a little") and those who rated the degree
      of bother as severe ("a lot" or "extremely"). Factors associated with severe
      symptoms and total SSPedi scores were examined using multiple logistic and linear
      regression. Among the 302 patients, 298 (98.7%) reported having any bothersome
      symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple
      regression, older children were significantly more likely to have at least one
      severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and
      to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were
      more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95%
      confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to
      have higher symptom scores (beta = 3.48, standard error = 1.6; P = 0.030). Almost
      all children receiving cancer therapies experience bothersome symptoms and 60%
      have at least one severely bothersome symptom. Older children experienced more
      severely bothersome symptoms and higher symptom scores. Future studies should
      follow children longitudinally to better understand the symptom trajectory and
      should institute interventions to manage symptoms.

PMID- 29573198
TI  - Formation of stromatolite lamina at the interface of oxygenic-anoxygenic
      photosynthesis.
AB  - In modern stromatolites, mineralization results from a complex interplay between
      microbial metabolisms, the organic matrix, and environmental parameters. Here, we
      combined biogeochemical, mineralogical, and microscopic analyses with
      measurements of metabolic activity to characterize the mineralization processes
      and products in an emergent (<18 months) hypersaline microbial mat. While the
      nucleation of Mg silicates is ubiquitous in the mat, the initial formation of a
      Ca-Mg carbonate lamina depends on (i) the creation of a high-pH interface
      combined with a major change in properties of the exopolymeric substances at the
      interface of the oxygenic and anoxygenic photoautotrophic layers and (ii) the
      synergy between two major players of sulfur cycle, purple sulfur bacteria, and
      sulfate-reducing bacteria. The repetition of this process over time combined with
      upward growth of the mat is a possible pathway leading to the formation of a
      stromatolite.

PMID- 29573199
TI  - NOTCH1 mutation and its prognostic significance in Chinese chronic lymphocytic
      leukemia: a retrospective study of 317 cases.
AB  - The proto-oncogene NOTCH1 is frequently mutated in around 10% of patients with
      chronic lymphocytic leukemia (CLL). This study analyzed NOTCH1 mutation status of
      317 Chinese patients with CLL by Sanger sequencing. The frequencies of NOTCH1
      mutation in the PEST (proline (P), glutamic acid (E), serine (S), threonine (T)
      rich protein sequence) domain and the 3' untranslated regions (UTR) were 8.2% and
      0.9%, with the most frequent mutation being c.7541_7542delCT and c.*371A>G,
      respectively. Clinical and biological associations were determined including
      NOTCH1 mutations with advanced stage (Binet stage, P = 0.010), unmutated
      immunoglobulin heavy-chain variable region (IGHV) gene (P < 0.001) and trisomy 12
      (+12) (P = 0.014). NOTCH1-mutated patients had lower CD20 expression intensity
      than NOTCH1-unmutated patients (P = 0.029). In addition, NOTCH1-mutated patients
      had shorter overall survival (OS) (P = 0.002) and treatment-free survival (TFS)
      (P = 0.002) than NOTCH1-unmutated patients, especially for patients with NOTCH1
      c.7541_7542delCT and/or c.*371A>G mutations. Patients with both mutated NOTCH1
      and unmutated IGHV had shorter OS (P < 0.001) and TFS (P < 0.001) than those with
      unmutated NOTCH1 or mutated IGHV. These data provide a comprehensive view of the
      clinical relevance and prognostic impact of NOTCH1 mutations on Chinese patients
      with CLL.

PMID- 29573200
TI  - Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on
      chondrosarcoma via activating peroxisome proliferator-activated receptor gamma
      and suppressing matrix metalloproteinase-2 expression.
AB  - Surgical resection is the only treatment for chondrosarcomas, because of their
      resistance to chemotherapy and radiotherapy; therefore, additional strategies are
      crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor
      gamma (PPARgamma) is a ligand-activated transcription factor, which has been
      reported as a possible therapeutic target in certain malignancies including
      chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti
      inflammatory drug, zaltoprofen, could induce PPARgamma activation and elicit anti
      tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce
      expressions of PPARgamma mRNA and protein in human chondrosarcoma SW1353 and
      OUMS27 cells, and induce PPARgamma-responsible promoter reporter activities.
      Inhibitory effects of zaltoprofen were observed on cell viability, proliferation,
      migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2);
      these effects were dependent on PPARgamma activation and evidenced by silencing
      PPARgamma. Moreover, we showed a case of a patient with cervical chondrosarcoma
      (grade 2), who was treated with zaltoprofen and has been free from disease
      progression for more than 2 years. Histopathological findings revealed enhanced
      expression of PPARgamma and reduced expression of MMP2 after administration of
      zaltoprofen. These findings demonstrate that zaltoprofen could be a promising
      drug against the malignant phenotypes in chondrosarcomas via activation of
      PPARgamma and inhibition of MMP2 activity.

PMID- 29573201
TI  - Intake of bean fiber, beans, and grains and reduced risk of hormone receptor
      negative breast cancer: the San Francisco Bay Area Breast Cancer Study.
AB  - High dietary fiber intake has been associated with reduced breast cancer risk,
      but few studies considered tumor subtypes defined by estrogen receptor (ER) and
      progesterone receptor (PR) status or included racial/ethnic minority populations
      who vary in their fiber intake. We analyzed food frequency data from a population
      based case-control study, including 2135 breast cancer cases (1070 Hispanics, 493
      African Americans, and 572 non-Hispanic Whites (NHWs)) and 2571 controls (1391
      Hispanics, 557 African Americans, and 623 NHWs). Odds ratios (OR) and 95%
      confidence intervals (CI) for breast cancer associated with fiber intake were
      calculated using unconditional logistic regression. Breast cancer risk associated
      with high intake (high vs. low quartile) of bean fiber (p-trend = 0.01), total
      beans (p-trend = 0.03), or total grains (p-trend = 0.05) was reduced by 20%.
      Inverse associations were strongest for ER-PR- breast cancer, with risk
      reductions associated with high intake ranging from 28 to 36%. For bean fiber,
      risk was reduced among foreign-born Hispanics only, who had the highest fiber
      intake, whereas for grain intake, inverse associations were found among NHWs
      only. There was no evidence of association with fiber intake from vegetables and
      fruits or total intake of vegetables and fruits. A high dietary intake of bean
      fiber and fiber-rich foods such as beans and grains may lower the risk of ER-PR-
      breast cancer, an aggressive breast cancer subtype for which few risk factors
      have been identified.

PMID- 29573203
TI  - Cruciferous Vegetables and Risk of Cancers of the Gastrointestinal Tract.
AB  - Cancers of the oropharyngeal tissues, oesophagus, stomach, and colorectum are
      amongst the most common causes of death from cancer throughout the world. Higher
      consumption of fruits and vegetables is thought to be protective, and cruciferous
      vegetables are of particular interest because of their unique role as a source of
      biologically active glucosinolate breakdown products. A literature review of
      primary studies and meta-analyses indicates that higher consumption of
      cruciferous vegetables probably reduces the risk of colorectal and gastric
      cancers by approximately 8% and 19%, respectively. Some studies support the
      hypothesis that the protective effect against colorectal cancer is modified by
      genetic polymorphisms of genes regulating the expression of enzymes of the
      glutathione S-transferase family, but due to contradictory findings the evidence
      is currently inconclusive. Despite these promising findings, future
      epidemiological research on the protective effects of cruciferous plants will
      depend critically upon accurate measurement of dietary exposure, both to the
      vegetables themselves, and to their active constituents. The development of
      sensitive chemical assays has facilitated the measurement of urinary excretion of
      isothiocyanate metabolites as an objective biomarker of intake, but sampling
      strategies need to be optimized in order to assess long-term exposures at the
      population level.

PMID- 29573202
TI  - Localization and dynamics of Wolbachia infection in Asian citrus psyllid
      Diaphorina citri, the insect vector of the causal pathogens of Huanglongbing.
AB  - Wolbachia is a group of intracellular bacteria that infect a wide range of
      arthropods including the Asian citrus psyllid (ACP), Diaphorina citri Kuwayama.
      This insect is the vector of Candidatus Liberibacter asiaticus (CLas), the causal
      pathogen of Huanglongbing or citrus greening disease. Here, we investigated the
      localization pattern and infection dynamics of Wolbachia in different
      developmental stages of ACP. Results revealed that all developmental stages of
      ACP including egg, 1st-5th instar nymphs, and adults of both gender were infected
      with Wolbachia. FISH visualization of an ACP egg showed that Wolbachia moved from
      the egg stalk of newly laid eggs to a randomly distributed pattern throughout the
      egg prior to hatching. The infection rate varied between nymphal instars. The
      titers of Wolbachia in fourth and fifth instar nymphs were significantly higher
      than those in the first and second instar nymphs. Wolbachia were scattered in all
      nymphal stages, but with highest intensity in the U-shaped bacteriome located in
      the abdomen of the nymph. Wolbachia was confined to two symmetrical organizations
      in the abdomen of newly emerged female and male adults. The potential mechanisms
      of Wolbachia infection dynamics are discussed.

PMID- 29573204
TI  - Intermediate filament protein evolution and protists.
AB  - Metazoans evolved from a single protist lineage. While all eukaryotes share a
      conserved actin and tubulin-based cytoskeleton, it is commonly perceived that
      intermediate filaments (IFs), including lamin, vimentin or keratin among many
      others, are restricted to metazoans. Actin and tubulin proteins are conserved
      enough to be detectable across all eukaryotic genomes using standard phylogenetic
      methods, but IF proteins, in contrast, are notoriously difficult to identify by
      such means. Since the 1950s, dozens of cytoskeletal proteins in protists have
      been identified that seemingly do not belong to any of the IF families described
      for metazoans, yet, from a structural and functional perspective fit criteria
      that define metazoan IF proteins. Here, we briefly review IF protein discovery in
      metazoans and the implications this had for the definition of this protein
      family. We argue that the many cytoskeletal and filament-forming proteins of
      protists should be incorporated into a more comprehensive picture of IF evolution
      by aligning it with the recent identification of lamins across the phylogenetic
      diversity of eukaryotic supergroups. This then brings forth the question of how
      the diversity of IF proteins has unfolded. The evolution of IF proteins likely
      represents an example of convergent evolution, which, in combination with the
      speed with which these cytoskeletal proteins are evolving, generated their
      current diversity. IF proteins did not first emerge in metazoa, but in protists.
      Only the emergence of cytosolic IF proteins that appear to stem from a nuclear
      lamin is unique to animals and coincided with the emergence of true animal
      multicellularity.

PMID- 29573205
TI  - Plasma miRNA can detect colorectal cancer, but how early?
AB  - Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good
      prognosis if detected early. The need for efficient, preferable non- or minimally
      invasive, inexpensive screening tools is therefore critical. We analyzed 12
      miRNAs in pre- and postdiagnostic plasma samples to evaluate their potential as
      CRC screening markers. We used a unique study design with two overlapping
      cohorts, allowing analysis of pre- and postdiagnostic samples from 58 patients
      with CRC and matched healthy controls. Plasma concentrations of miR-15b, -16, 
      18a, -19a, 21, -22, -25, -26a, -29c, -142-5p, -150, and -192 were measured by
      semi-quantitative real-time PCR. Concentrations of miR-18a, -21, -22, and -25 in
      plasma from patients with CRC were significantly altered compared to healthy
      controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93.
      Furthermore, levels of these three miRNAs also showed different levels in the
      prediagnostic case samples close to diagnosis. Only miR-21-levels were elevated
      several years before diagnosis. Plasma levels of miR-18a, -21, -22, and -25 show
      promise as screening biomarkers for CRC. However, based on our unique analysis of
      prediagnostic and postdiagnostic samples from the same patients, we conclude that
      circulating miRNAs elevated at diagnosis may not automatically be suitable for
      CRC screening, if the increase occurs too close to clinical diagnosis.

PMID- 29573206
TI  - Identification of transcriptome signature for predicting clinical response to
      bevacizumab in recurrent glioblastoma.
AB  - Glioblastomas are among the most fatal brain tumors. Although no effective
      treatment option is available for recurrent glioblastomas (GBMs), a subset of
      patients evidently derived clinical benefit from bevacizumab, a monoclonal
      antibody against vascular endothelial growth factor. We retrospectively reviewed
      patients with recurrent GBM who received bevacizumab to identify biomarkers for
      predicting clinical response to bevacizumab. Following defined criteria, the
      patients were categorized into two clinical response groups, and their genetic
      and transcriptomic results were compared. Angiogenesis-related gene sets were
      upregulated in both responders and nonresponders, whereas genes for each
      corresponding angiogenesis pathway were distinct from one another. Two gene sets
      were made, namely, the nonresponder angiogenesis gene set (NAG) and responder
      angiogenesis gene set (RAG), and then implemented in independent GBM cohort to
      validate our dataset. A similar association between the corresponding gene set
      and survival was observed. In NAG, COL4A2 was associated with a poor clinical
      outcome in bevacizumab-treated patients. This study demonstrates that
      angiogenesis-associated gene sets are composed of distinct subsets with diverse
      biological roles and they represent different clinical responses to anti
      angiogenic therapy. Enrichment of a distinct angiogenesis pathway may serve as a
      biomarker to predict patients who will derive a clinical benefit from
      bevacizumab.

PMID- 29573207
TI  - An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth
      factor, in breast cancer.
AB  - This randomized, open-label, active-controlled study investigated the safety and
      efficacy of three doses of Rolontis (eflapegrastim), a novel, long-acting myeloid
      growth factor, versus pegfilgrastim in breast cancer patients being treated with
      docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration
      of severe neutropenia (DSN) during the first cycle of treatment. Patients who
      were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for
      participation. TC was administered on Day 1, followed by 45, 135, or 270 MUg/kg
      Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored
      daily when the absolute neutrophil count (ANC) fell to <1.5 * 109 /L. Up to four
      cycles of TC were investigated. The difference in DSN (time from ANC <0.5 * 109
      /L to ANC recovery >=2.0 * 109 /L) between the Rolontis and pegfilgrastim groups
      was -0.28 days (confidence interval [CI]: -0.56, -0.06) at 270 MUg/kg, 0.14 days
      (CI: -0.28, 0.64) at 135 MUg/kg, and 0.72 days (CI: 0.19, 1.27) at 45 MUg/kg.
      Noninferiority to pegfilgrastim was demonstrated at 135 MUg/kg (P = 0.002) and
      270 MUg/kg (P < .001), with superiority demonstrated at 270 MUg/kg (0.03 days; P
      = 0.023). The most common treatment-related adverse events (AEs) were bone pain,
      myalgia, arthralgia, back pain, and elevated white blood cell counts, with
      similar incidences across groups. All doses of Rolontis were well tolerated, and
      no new or significant treatment-related toxicities were observed. In Cycle 1,
      Rolontis demonstrated noninferiority at the 135 MUg/kg dose and statistical
      superiority in DSN at the 270 MUg/kg dose when compared to pegfilgrastim.

PMID- 29573208
TI  - Correlating colorectal cancer risk with field carcinogenesis progression using
      partial wave spectroscopic microscopy.
AB  - Prior to the development of a localized cancerous tumor, diffuse molecular, and
      structural alterations occur throughout an organ due to genetic, environmental,
      and lifestyle factors. This process is known as field carcinogenesis. In this
      study, we used partial wave spectroscopic (PWS) microscopy to explore the
      progression of field carcinogenesis by measuring samples collected from 190
      patients with a range of colonic history (no history, low-risk history, and high
      risk history) and current colon health (healthy, nondiminutive adenomas (NDA; >=5
      mm and <10 mm), and advanced adenoma [AA; >=10 mm, HGD, or >25% villous
      features]). The low-risk history groups include patients with a history of NDA.
      The high-risk history groups include patients with either a history of AA or
      colorectal cancer (CRC). PWS is a nanoscale-sensitive imaging technique which
      measures the organization of intracellular structure. Previous studies have shown
      that PWS is sensitive to changes in the higher-order (20-200 nm) chromatin
      topology that occur due to field carcinogenesis within histologically normal
      cells. The results of this study show that these nanoscale structural alterations
      are correlated with a patient's colonic history, which suggests that PWS can
      detect altered field carcinogenic signatures even in patients with negative
      colonoscopies. Furthermore, we developed a model to calculate the 5-year risk of
      developing CRC for each patient group. We found that our data fit this model
      remarkably well (R2  = 0.946). This correlation suggests that PWS could
      potentially be used to monitor CRC progression less invasively and in patients
      without adenomas, which opens PWS to many potential cancer care applications.

PMID- 29573209
TI  - Regulatory role of the RstB-RstA system in adhesion, biofilm production,
      motility, and hemolysis.
AB  - For infection, initial invasion of the host is of great importance, with adhesion
      playing a critical role. We previously demonstrated rstA and rstB are remarkably
      downregulated in Vibrio alginolyticus cultured under heavy metal and acidic
      stresses, with impaired adhesion, suggesting that rstA and rstB might be involved
      in adhesion regulation. The present study showed that rstA and rstB silencing
      resulted in impaired adhesion, biofilm production, motility, hemolysis, and
      virulence. Meanwhile, changes of temperature, starvation, and pH remarkably
      affected rstA and rstB expression. These findings indicated that (1) rstA and
      rstB are critical regulators of adhesion in V. alginolyticus; (2) rstA and rstB
      have remarkable effects on biofilm production, motility, hemolysis, and virulence
      in V. alginolyticus; (3) rstA and rstB modulate adhesion in response to
      environmental changes of temperature, pH, and starvation.

PMID- 29573210
TI  - Human papillomavirus and survival of patients per histological subsite of
      tonsillar squamous cell carcinoma.
AB  - Current data advocate that oropharyngeal squamous cell carcinoma (OPSCC) should
      be divided into subsites when evaluating the presence of human papillomavirus
      (HPV) and prognosis. More specifically, tonsillar squamous cell carcinoma (TSCC)
      and base of tongue squamous cell carcinoma (BOTSCC) have much higher HPV
      prevalence compared to other OPSCC. Moreover, patients with HPV positive (HPV+)
      TSCC and BOTSCC have a better prognosis as compared to patients with HPV negative
      (HPV-) corresponding tumors, while the prognostic role of HPV in other OPSCC is
      unclear. Furthermore, in a recent report from Denmark, TSCC was further
      subclassified into specified TSCC (STSCC) and nonspecified TSCC (NSTSCC), with
      HPV significantly more prevalent in STSCC. In this study, the histopathological
      influence of HPV prevalence and survival in TSCC was analyzed in a TSCC cohort
      with known HPV status, of patients diagnosed 1970-2002 in Stockholm. In total,
      139 TSCC biopsies with both tumor and adjacent normal tissue were separated into
      STSCC and NSTSCC. HPV was significantly more commonly found in STSCC than in
      NSTSCC. Patients with HPV+ STSCC had a better disease-specific and overall
      survival as compared to patients with HPV+ NSTSCC, but no survival differences
      were observed in patients with HPV- STSCC and NSTCC. These findings confirm
      previous reports and suggest that TSCC subsite may also be of relevance for
      clinical outcome and should be further followed up in future studies.

PMID- 29573211
TI  - Tannerella forsythia-produced methylglyoxal causes accumulation of advanced
      glycation endproducts to trigger cytokine secretion in human monocytes.
AB  - The periodontal pathogen Tannerella forsythia has the unique ability to produce
      methylglyoxal (MGO), an electrophilic compound which can covalently modify amino
      acid side chains and generate inflammatory adducts known as advanced glycation
      endproducts (AGEs). In periodontitis, concentrations of MGO in gingival
      crevicular fluid are increased and are correlated with the T. forsythia load.
      However, the source of MGO and the extent to which MGO may contribute to
      periodontal inflammation has not been fully explored. In this study we identified
      a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the
      production of MGO in T. forsythia. While wild-type T.forsythia produced a
      significant amount of MGO in the medium, a mutant lacking this homolog produced
      little to no MGO. Furthermore, compared with the spent medium of the T. forsythia
      parental strain, the spent medium of the T. forsythia mgsA-deletion strain
      induced significantly lower nuclear factor-kappa B activity as well as
      proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The
      ability of T. forsythia to induce protein glycation endproducts via MGO was
      confirmed by an electrophoresis-based collagen chain mobility shift assay.
      Together these data demonstrated that T. forsythia produces MGO, which may
      contribute to inflammation via the generation of AGEs and thus act as a potential
      virulence factor of the bacterium.

PMID- 29573213
TI  - Identification of Clostridium difficile Immunoreactive Spore Proteins of the
      Epidemic Strain R20291.
AB  - PURPOSE: Clostridium difficile infections are the leading cause of diarrhea
      associated with the use of antibiotics. During infection, C. difficile initiates
      a sporulation cycle leading to the persistence of C. difficile spores in the host
      and disease dissemination. The development of vaccine and passive immunization
      therapies against C. difficile has focused on toxins A and B. In this study, an
      immunoproteome-based approach to identify immunogenic proteins located on the
      outer layers of C. difficile spores as potential candidates for the development
      of immunotherapy and/or diagnostic methods against this devastating infection is
      used. EXPERIMENTAL DESIGN: To identify potential immunogenic proteins on the
      surface of C. difficile R20291, spore coat/exosporium extracts are separated by
      2D electrophoresis (2-DE) and analyzed for reactivity against C. difficile spore
      specific goat sera. Finally, the selected spots are in-gel digested with
      chymotrypsin, peptides generated are separated by nanoUPLC followed by MS/MS
      using Quad-TOF-MS, corroborated by Ultimate 3000RS-nano-UHPLC coupled to Q
      Exactive-Plus-Orbitrap MS. RESULTS: The analysis identify five immunoreactive
      proteins: spore coat proteins CotE, CotA, and CotCB; exosporium protein CdeC; and
      a cytosolic methyltransferase. CONCLUSION: This data provides a list of spore
      surface protein candidates as antigens for vaccine development against C.
      difficile infections.

PMID- 29573212
TI  - Medication use in infants admitted with bronchiolitis.
AB  - BACKGROUND: There are no medications known that improve the outcome of infants
      with bronchiolitis. Studies have shown the management of bronchiolitis to be
      varied. OBJECTIVES: To describe medication use at the seven study hospitals from
      a recent multi-centre randomised controlled trial on hydration in bronchiolitis
      (comparative rehydration in bronchiolitis [CRIB]). METHODS: A retrospective
      analysis of extant data of infants between 2 months (corrected for prematurity)
      and 12 months of age admitted with bronchiolitis identified through the CRIB
      trial. CRIB study records, medical records, pathology and radiology databases
      were used to collect data using a standardised form and entered in a single site
      database. Medications investigated included salbutamol, adrenaline, steroids,
      ipratropium bromide, normal saline, hypertonic saline, steroids and antibiotics.
      RESULTS: There were 3456 infants available for analysis, of which 42.0% received
      at least one medication during hospitalisation. Medication use varied by site
      between 27.0 and 48.7%. The most frequently used medication was salbutamol
      (25.5%). Medication use in general, and salbutamol use in particular, increased
      by 8.2 and 9.3%, respectively, per month after 4 months of age; from 22.9 and
      3.6% at 4 months to 81.4 and 68.8% at 11 months. In infants admitted to the
      intensive care unit (ICU) compared with those not admitted to ICU 81.6 and 39.5%,
      respectively, received medication at one point during the hospital stay.
      CONCLUSIONS: Medication was used for infants with bronchiolitis frequently and
      variably in Australia and New Zealand. Medication use increased with age. Better
      strategies for translating evidence into practice are needed.

PMID- 29573215
TI  - Longitudinal medical resources and costs among type 2 diabetes patients
      participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin
      (TECOS).
AB  - AIMS: TECOS, a cardiovascular safety trial (ClinicalTrials.gov identifier:
      NCT00790205) involving 14 671 patients with type 2 diabetes and cardiovascular
      disease, demonstrated that sitagliptin was non-inferior to placebo for the
      primary composite cardiovascular outcome when added to best usual care. This
      study tested hypotheses that medical resource use and costs differed between
      these 2 treatment strategies. MATERIALS AND METHODS: Information concerning
      medical resource use was collected on case report forms throughout the trial and
      was valued using US costs for: Medicare payments for hospitalizations, medical
      procedures and outpatient visits, and wholesale acquisition costs (WAC) for
      diabetes-related medications. Hierarchical generalized linear models were used to
      compare resource use and US costs, accounting for variable intercountry practice
      patterns. Sensitivity analyses included resource valuation using English costs
      for a UK perspective. RESULTS: There were no significant differences in
      hospitalizations, inpatient days, medical procedures, or outpatient visits during
      follow-up (mean and median 3.0 years in both groups). Hospitalization rates
      appeared to diverge after 2 years, with lower rates among sitagliptin-treated vs
      placebo patients after 2.5 years (relative rate, 0.90 [95% CI, 0.83-0.97]; P =
      .01). Mean medical costs, exclusive of study medication, were 11 937 USD in the
      sitagliptin arm and 12 409 USD in the placebo arm (P = .06). Mean sitagliptin
      costs based on undiscounted WAC were 9978 USD per patient. Differential UK total
      costs including study drug costs were smaller (911 GBP), primarily because of
      lower mean costs for sitagliptin (1072 GBP). CONCLUSIONS: Lower hospitalization
      rates across time with sitagliptin slightly offset sitagliptin treatment costs
      over 3 years in type 2 diabetes patients at high risk for cardiovascular events.

PMID- 29573214
TI  - Re-irradiation of recurrent gliomas: pooled analysis and validation of an
      established prognostic score-report of the Radiation Oncology Group (ROG) of the
      German Cancer Consortium (DKTK).
AB  - The heterogeneity of high-grade glioma recurrences remains an ongoing challenge
      for the interdisciplinary neurooncology team. Response to re-irradiation (re-RT)
      is heterogeneous, and survival data depend on prognostic factors such as tumor
      volume, primary histology, age, the possibility of reresection, or time between
      primary diagnosis and initial RT and re-RT. In the present pooled analysis, we
      gathered data from radiooncology centers of the DKTK Consortium and used it to
      validate the established prognostic score by Combs et al. and its modification by
      Kessel et al. Data consisted of a large independent, multicenter cohort of 565
      high-grade glioma patients treated with re-RT from 1997 to 2016 and a median dose
      of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy.
      Median age was 54 years; median follow-up was 7.1 months. Median OS after re-RT
      was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively.
      All six prognostic factors were tested for their significance on OS. Aside from
      the time from primary RT to re-RT (P = 0.074) and the reresection status (P =
      0.101), all factors (primary histology, age, KPS, and tumor volume) were
      significant. Both the original and new score showed a highly significant
      influence on survival with P < 0.001. Both prognostic scores successfully predict
      survival after re-RT and can easily be applied in the routine clinical workflow.
      Now, further prognostic features need to be found to even improve treatment
      decisions regarding neurooncological interventions for recurrent glioma patients.

PMID- 29573216
TI  - Glucose impairments and insulin resistance in prostate cancer: the role of
      obesity, nutrition and exercise.
AB  - BACKGROUND: Hyperinsulinemia, obesity and related metabolic diseases are
      associated with prostate cancer development. Prostate cancer patients undergoing
      androgen deprivation therapy (ADT) are at increased risk for metabolic syndrome,
      cardiovascular disease and diabetes, while pre-existing metabolic conditions may
      be exacerbated. PURPOSE: An integrative approach is used to describe the
      interactions between insulin, glucose metabolism, obesity and prostate cancer.
      The potential role of nutrition and exercise will also be examined. FINDINGS:
      Hyperinsulinemia is associated with prostate cancer development, progression and
      aggressiveness. Prostate cancer patients who undergo ADT are at risk of diabetes
      in survivorship. It is unclear whether this is a direct result of treatment or
      related to pre-existing metabolic features (e.g. hyperinsulinemia and obesity).
      Obesity and metabolic syndrome are also associated with prostate cancer
      development and poorer outcomes for cancer survivors, which may be driven by
      hyperinsulinemia, pro-inflammation, hyperleptinemia and/or hypoadiponectinemia.
      CONCLUSIONS: Independently evaluating changes in glucose metabolism near the time
      of prostate cancer diagnosis and during long-term ADT treatment is important to
      distinguish their unique contributions to the development of metabolic
      disturbances. Integrative approaches, including metabolic, clinical and body
      composition measures, are needed to understand the role of adiposity and insulin
      resistance in prostate cancer and to develop effective nutrition and exercise
      interventions to improve secondary diseases in survivorship.

PMID- 29573217
TI  - The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm
      meta-analysis of noncomparative clinical studies and randomized controlled
      trials.
AB  - Nivolumab is a programmed cell death 1 (PD-1) receptor inhibitor antibody that
      enhances immune system antitumor activity. Although it is used for treating
      advanced non-small-cell lung cancer (NSCLC), its actual efficacy has not been
      determined. We searched PubMed, the Cochrane Library, Embase, MEDLINE, and Web of
      Science for related noncomparative clinical studies and randomized controlled
      trials (RCTs) to assess nivolumab benefit and risk in NSCLC. The main outcomes
      were objective response rate (ORR), 1-year overall survival rate (1-yOS rate),
      and progression-free survival rate at 24 weeks (PFS at 24 weeks rate), any-grade
      adverse effects rate (any-grade AEs%), and grade 3-4 AE rate (grade 3-4 AEs%).
      Relative risk (RR) was used to compare ORR in patients with positive and negative
      programmed cell death ligand 1 (PD-L1) expression. Random-effects models were
      used to determine pooled effect size and two-sided 95% confidence intervals (95%
      CI). We included 20 studies (17 noncomparative open-label cohort studies, three
      RCTs) involving 3404 patients in our meta-analysis. The modified nivolumab ORR
      was 18% (95% CI: 15-20%), the 1-yOS rate was 45% (95% CI: 40-50%), PFS at 24
      weeks rate was 42% (95% CI: 37-48%), any-grade AEs% was 61% (95% CI: 50-73%), and
      grade 3-4 AEs% was 12% (95% CI: 9-16%). PD-L1 expression was related with the
      nivolumab ORR. Nivolumab potentially causes ongoing response, long-term PFS, and
      reduced treatment-related AEs. PD-L1 expression predicts the outcome of nivolumab
      immunotherapy. More high-quality and well-designed RCTs with large sample sizes
      are warranted to prove our findings.

PMID- 29573218
TI  - Understanding environmental contributions to autism: Causal concepts and the
      state of science.
AB  - : The complexity of neurodevelopment, the rapidity of early neurogenesis, and
      over 100 years of research identifying environmental influences on
      neurodevelopment serve as backdrop to understanding factors that influence risk
      and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered
      at the May 2016 annual meeting of the International Society for Autism Research,
      describes concepts of causation, outlines the trajectory of research on
      nongenetic factors beginning in the 1960s, and briefly reviews the current state
      of this science. Causal concepts are introduced, including root causes; pitfalls
      in interpreting time trends as clues to etiologic factors; susceptible time
      windows for exposure; and implications of a multi-factorial model of ASD. An
      historical background presents early research into the origins of ASD. The
      epidemiologic literature from the last fifteen years is briefly but critically
      reviewed for potential roles of, for example, air pollution, pesticides,
      plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric
      and metabolic conditions during her pregnancy. Three examples from the case
      control CHildhood Autism Risks from Genes and the Environment Study are probed to
      illustrate methodological approaches to central challenges in observational
      studies: capturing environmental exposure; causal inference when a randomized
      controlled clinical trial is either unethical or infeasible; and the integration
      of genetic, epigenetic, and environmental influences on development. We conclude
      with reflections on future directions, including exposomics, new technologies,
      the microbiome, gene-by-environment interaction in the era of -omics, and
      epigenetics as the interface of those two. As the environment is malleable, this
      research advances the goal of a productive and fulfilling life for all children,
      teen-agers and adults. Autism Res 2018, 11: 554-586. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This Keynote
      Lecture, delivered at the 2016 meeting of the International Society for Autism
      Research, discusses evidence from human epidemiologic studies of prenatal factors
      contributing to autism, such as pesticides, maternal nutrition and her health.
      There is no single cause for autism. Examples highlight the features of a high
      quality epidemiology study, and what comprises a compelling case for causation.
      Emergent research directions hold promise for identifying potential interventions
      to reduce disabilities, enhance giftedness, and improve lives of those with ASD.

PMID- 29573219
TI  - Predicting loneliness with polygenic scores of social, psychological and
      psychiatric traits.
AB  - Loneliness is a heritable trait that accompanies multiple disorders. The
      association between loneliness and mental health indices may partly be due to
      inherited biological factors. We constructed polygenic scores for 27 traits
      related to behavior, cognition and mental health and tested their prediction for
      self-reported loneliness in a population-based sample of 8798 Dutch individuals.
      Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar
      disorder were significantly associated with loneliness. Of the Big Five
      personality dimensions, polygenic scores for neuroticism and conscientiousness
      also significantly predicted loneliness, as did the polygenic scores for
      subjective well-being, tiredness and self-rated health. When including all
      polygenic scores simultaneously into one model, only 2 major depression polygenic
      scores remained as significant predictors of loneliness. When controlling only
      for these 2 MDD polygenic scores, only neuroticism and schizophrenia remain
      significant. The total variation explained by all polygenic scores collectively
      was 1.7%. The association between the propensity to feel lonely and the
      susceptibility to psychiatric disorders thus pointed to a shared genetic
      etiology. The predictive power of polygenic scores will increase as the power of
      the genome-wide association studies on which they are based increases and may
      lead to clinically useful polygenic scores that can inform on the genetic
      predisposition to loneliness and mental health.

PMID- 29573220
TI  - Depleted iron stores are associated with inspiratory muscle weakness
      independently of skeletal muscle mass in men with systolic chronic heart failure.
AB  - BACKGROUND: Skeletal and respiratory muscle dysfunction constitutes an important
      pathophysiological feature of heart failure (HF). We assessed the relationships
      between respiratory muscle function, skeletal muscle mass, and physical fitness
      in men with HF with reduced left ventricular ejection fraction (HFrEF), and
      investigated the hypothesis of whether iron deficiency (ID) contributes to
      respiratory muscle dysfunction in these patients. METHODS: We examined 53 male
      outpatients with stable HFrEF without asthma or chronic obstructive pulmonary
      disease (age: 64 +/- 10 years; New York Heart Association [NYHA] class I/II/III:
      36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction
      <=40%) and 10 middle-aged healthy men (control group). We analysed respiratory
      muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP
      and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was
      measured using dual-energy X-ray absorptiometry), physical fitness (components of
      Functional Fitness Test for Older Adults), and iron status. RESULTS: MIP, MEP,
      and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs.
      healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower
      in men with HFrEF with vs. without ID. In a multivariable linear regression model
      lower serum ferritin (but not transferrin saturation) was associated with lower
      MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro
      B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In
      multivariable linear regression models, lower MIP was associated with worse
      results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical
      variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and
      haemoglobin concentration). CONCLUSIONS: In men with HFrEF, low ferritin
      reflecting depleted iron stores is associated with inspiratory muscle weakness
      independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates
      with worse physical fitness independently of either skeletal muscle mass or
      disease severity.

PMID- 29573221
TI  - Glycemic extremes are related to cognitive dysfunction in children with type 1
      diabetes: A meta-analysis.
AB  - AIMS/INTRODUCTION: To examine the magnitude and pattern of cognitive dysfunction
      in children with type 1 diabetes, and the possible effects associated with other
      disease variables, such as early onset diabetes, severe hypoglycemia and
      hyperglycemia. MATERIALS AND METHODS: We carried out a meta-analysis using the
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We
      searched MedLine, Embase and PsycINFO to identify studies on cognitive function
      in children with type 1 diabetes that were published up until 30 September 2016.
      Effect sizes understood as the standardized mean differences between groups with
      diabetes and control groups (i.e., Hedges' g) were calculated to quantify the
      extent of cognitive dysfunction in those groups consisting of children with
      diabetes. RESULTS: A total of 19 studies met our inclusion criteria, comprising
      1,355 participants with type 1 diabetes and 696 controls. Compared with non
      diabetic controls, children with type 1 diabetes showed a significantly poorer
      cognitive performance overall (g = -0.46), as well as specific deficits in full
      scale intelligence (g = -1.06), attention (g = -0.60) and psychomotor speed (g = 
      0.46). Glycemic extremes were associated with poorer overall cognition (g = 
      0.18), as well as slightly lower performance in memory (g = -0.27). CONCLUSIONS:
      We found that type 1 diabetes was associated with cognitive dysfunction
      characterized by a lowered intelligence, diminished attention and a slowing of
      psychomotor speed. Glycemic extremes, which are described as a period of high
      glucose levels and severe hypoglycemia, were related to cognitive dysfunction in
      children with type 1 diabetes.

PMID- 29573223
TI  - Mycobiota of maize seeds revealed by rDNA-ITS sequence analysis of samples with
      varying storage times.
AB  - Fungi are an integral component of the plant microbiome. However, the composition
      and variation in the fungal communities (mycobiota) associated with seeds are
      poorly understood. In this study, we investigated the mycobiota of 11 maize seed
      samples with storage times ranging from 6 months to 12 years. Mycobiota were
      characterized by a culture-based approach, and fungal species were identified
      through rDNA-ITS sequence analyses. From a total of 169 pure fungal isolates
      obtained from both the seed surface and internal tissues, we identified 16
      distinct species (belonging to 10 genera) associated with maize seeds, all but
      one of which were ascomycetes. Among these species, seven were exclusively
      isolated from internal tissues, two species were isolated only from the seed
      surface, and another six species were isolated from both the surface and internal
      tissues. Aspergillus niger was consistently found under all storage conditions
      and dominated fungal communities with a relative abundance of 36%-100%. Species
      of Fusarium (9%-40%) and Penicillium (9%-20%) were also frequently isolated, but
      other species appeared sporadically and were isolated from fewer than three seed
      stocks. According to our results, while the overall incidence of fungal infection
      generally declined with storage time, there was no consistent association between
      seed storage time and fungal species richness or relative abundance; furthermore,
      the composition of the mycobiota associated with maize seeds was highly variable
      among the samples. The detection of the four major mycotoxigenic fungal genera,
      specifically Aspergillus, Fusarium, Penicillium, and Alternaria, was alarming,
      and the isolation of a potential controlling agent as well as information about
      their temporal occurrence will contribute to the management of mycotoxins in the
      future.

PMID- 29573224
TI  - Mediterranean Diet, Glucose Homeostasis, and Inflammasome Genetic Variants: The
      CORDIOPREV Study.
AB  - SCOPE: Insulin resistance (IR) and chronic low-grade inflammation are hallmarks
      of type 2 diabetes mellitus (T2DM). The "NOD-like receptor pyrin domain
      containing-3" (NLRP3) inflammasome component of innate immunity is a metabolic
      stress sensor modulated by dietary and genetics factors. The aim of this study
      was to evaluate the effects of the consumption of two diets for 3 years,
      Mediterranean (Med) and low fat, on glucose homeostasis in the 1002 coronary
      heart disease patients of the CORDIOPREV study, according to a genetic variant of
      NLRP3 inflammasome. METHODS AND RESULTS: The study was conducted in the framework
      of the CORDIOPREV study, a randomized dietary intervention with Med and low-fat
      diets. Single nucleotide polymorphisms (SNPs) located at inflammasome NLRP3 gene
      were genotyped by OpenArray platform. Nondiabetic CT+TT carriers of the rs4612666
      SNP and AG+AA carriers of the rs10733113 SNP increased insulin sensitivity index
      (ISI) after 3 years of dietary intervention, whereas no effect was observed in
      diabetic patients. Further analysis by diet showed that the improvement of the
      ISI in nondiabetic rs10733113 AG+AA carriers was specific to the consumption of
      the Med diet. CONCLUSION: Our results show that the benefits associated with a
      Med diet regarding glucose homeostasis in non-T2DM patients depend on genetic
      variation in the inflammasome.

PMID- 29573222
TI  - Concise Review: Altered Versus Unaltered Amniotic Membrane as a Substrate for
      Limbal Epithelial Cells.
AB  - Limbal stem cell deficiency (LSCD) can result from a variety of corneal
      disorders, including chemical and thermal burns, infections, and autoimmune
      diseases. The symptoms of LSCD may include irritation, epiphora, blepharospasms,
      photophobia, pain, and decreased vision. There are a number of treatment options,
      ranging from nonsurgical treatments for mild LSCD to various forms of surgery
      that involve different cell types cultured on various substrates. Ex vivo
      expansion of limbal epithelial cells (LEC) involves the culture of LEC harvested
      either from the patient, a living relative, or a cadaver on a substrate in the
      laboratory. Following the transfer of the cultured cell sheet onto the cornea of
      patients suffering from LSCD, a successful outcome can be expected in
      approximately three out of four patients. The phenotype of the cultured cells has
      proven to be a key predictor of success. The choice of culture substrate is known
      to affect the phenotype. Several studies have shown that amniotic membrane (AM)
      can be used as a substrate for expansion of LEC for subsequent transplantation in
      the treatment of LSCD. There is currently a debate over whether AM should be
      denuded (i.e., de-epithelialized) prior to LEC culture, or whether this substrate
      should remain intact. In addition, crosslinking of the AM has been used to
      increase the thermal and mechanical stability, optical transparency, and
      resistance to collagenase digestion of AM. In the present review, we discuss the
      rationale for using altered versus unaltered AM as a culture substrate for LEC.
      Stem Cells Translational Medicine 2018;7:415-427.

PMID- 29573225
TI  - Concise Review: Stem Cell Fate Guided By Bioactive Molecules for Tendon
      Regeneration.
AB  - Tendon disorders, which are commonly presented in the clinical setting, disrupt
      the patients' normal work and life routines, and they damage the careers of
      athletes. However, there is still no effective treatment for tendon disorders. In
      the field of tissue engineering, the potential of the therapeutic application of
      exogenous stem cells to treat tendon pathology has been demonstrated to be
      promising. With the development of stem cell biology and chemical biology,
      strategies that use inductive tenogenic factors to program stem cell fate in situ
      are the most easily and readily translatable to clinical applications. In this
      review, we focus on bioactive molecules that can potentially induce tenogenesis
      in adult stem cells, and we summarize the various differentiation factors found
      in comparative studies. Moreover, we discuss the molecular regulatory mechanisms
      of tenogenesis, and we examine the various challenges in developing standardized
      protocols for achieving efficient and reproducible tenogenesis. Finally, we
      discuss and predict future directions for tendon regeneration. Stem Cells
      Translational Medicine 2018;7:404-414.

PMID- 29573226
TI  - Human papillomavirus detection with genotyping by the cobas and Aptima assays:
      Significant differences in HPV 16 detection?
AB  - BACKGROUND: The primary high-risk human papillomavirus (hrHPV) assays in the
      United States are the cobas (Roche) and the Aptima (Hologic). The cobas assay
      detects hrHPV by DNA analysis while the Aptima detects messenger RNA (mRNA)
      oncogenic transcripts. As the Aptima assay identifies oncogenic expression, it
      should have a lower rate of hrHPV and genotype detection. METHODS: The Kaiser
      Permanente Regional Reference Laboratory in Denver, Colorado changed its hrHPV
      assay from the cobas to the Aptima assay. The rates of hrHPV detection and
      genotyping were compared over successive six-month periods. RESULTS: The overall
      hrHPV detection rates by the two platforms were similar (9.5% versus 9.1%) and
      not statistically different. For genotyping, the HPV 16 rate by the cobas was
      1.6% and by the Aptima it was 1.1%. These differences were statistically
      different with the Aptima detecting nearly one-third less HPV 16 infections. With
      the HPV 18 and HPV 18/45, there was a slightly higher detection rate of HPV 18/45
      by the Aptima platform (0.5% versus 0.9%) and this was statistically significant.
      CONCLUSION: While HPV 16 represents a low percentage of hrHPV infections, it was
      detected significantly less by the Aptima assay compared to the cobas assay. This
      has been previously reported, although not highlighted. Given the test
      methodologies, one would expect the Aptima to detect less HPV 16. This difference
      appears to be mainly due to a significantly increased number of non-oncogenic HPV
      16 infections detected by the cobas test as there were no differences in HPV 16
      detection rates in the high-grade squamous intraepithelial lesions indicating
      that the two tests have similar sensitivities for oncogenic HPV 16.

PMID- 29573227
TI  - Patients' preoperative background causes gastric stasis after laparoscopy
      assisted pylorus-preserving gastrectomy.
AB  - INTRODUCTION: Despite technical improvements in laparoscopic gastrectomy, gastric
      stasis is still a serious problem in laparoscopy-assisted pylorus-preserving
      gastrectomy (LAPPG). The aim of this study was to investigate the factors that
      might cause gastric stasis in LAPPG. METHODS: From April 2004 through November
      2012, 85 patients with cT1N0 middle-third gastric cancer who underwent LAPPG at
      Kitasato University Hospital; these patients were included in the present study.
      Infra-pyloric vein (IPV)-preserving LAPPG was performed in 41 patients. We
      compared the rate of gastric stasis in the IPV-preserving and the IPV-non
      preserving groups, and analyzed the clinicopathological factors that might have
      caused gastric stasis. RESULTS: We did not demonstrate that preservation of the
      IPV could prevent gastric stasis in the early and late postoperative periods.
      Symptoms of gastric stasis were most frequently recognized 1 year after surgery.
      A significantly higher proportion of preoperative ASA class 2 patients had
      gastric stasis than did not (80.0% [12/15] vs 48.6% [34/70], P=0.02). Among the
      ASA class 2 patients, a significantly greater proportion of those with depressed
      activities of daily living than those with normal activities of daily living had
      gastric stasis (66.7% [4/6] vs 20.0% [8/40], P = 0.015). CONCLUSIONS: The
      clinical significance of the IPV preservation in LAPPG could not be demonstrated.
      LAPPG should be performed for ASA class 1 patients or those with maintained
      preoperative activities of daily living.

PMID- 29573229
TI  - Urinary tract blastomycosis diagnosed by urine cytology.
AB  - Urinary tract blastomycosis is an uncommon manifestation of disseminated
      Blastomyces infection. Here, we report a 50-year-old male with common variable
      immunodeficiency who presented with urinary symptoms and a renal mass concerning
      for a kidney neoplasm. Urine cytology revealed typical broad-based budding yeasts
      with thick-walled refractile capsules, leading to diagnosis of urinary tract
      blastomycosis. In this case, urine cultures were negative, and urine cytology was
      the main method of diagnosis of blastomycosis. Thus, urine cytology represents a
      rapid and reliable method of diagnosing blastomycosis, which in the current case
      led to prompt treatment of this potentially life threatening infection.

PMID- 29573228
TI  - A prospective study of soluble receptor for advanced glycation end products and
      adipokines in association with pancreatic cancer in postmenopausal women.
AB  - Advanced glycation end products (AGEs) dysregulate adipokines and induce
      inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE)
      prevents AGEs/RAGE signaling. We performed a nested case-control study of the
      association between sRAGE, adipokines, and incident pancreatic cancer risk in the
      prospective Women's Health Initiative Study. We individually matched controls (n
      = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum
      concentrations of sRAGE, adiponectin, leptin, monocyte chemotactic protein 1
      (MCP1), and plasminogen activator inhibitor-1 (PAI1) using immunoassay. We used
      conditional logistic regression model to estimate adjusted odds ratios (aORs) and
      95% confidence intervals (CIs) for pancreatic cancer over biomarker quartiles (Q1
      Q4). We used principal component analysis to create two composite biomarkers and
      performed a confirmatory factor analysis to examine the association between
      composite biomarker scores (CBS) and pancreatic cancer risk. Baseline serum sRAGE
      concentrations were inversely associated with pancreatic cancer risk (aORQ4 vs.
      Q1  = 0.70, 95% CI: 0.50-0.99). High MCP1 (aOR Q4 vs. Q1  = 2.55, 95% CI: 1.41
      4.61) and the higher CBS including MCP1, PAI1, and leptin (aORQ4 vs. Q1  = 1.82,
      95% CI = 1.04-3.18) were also associated with increased pancreatic cancer risk
      among women with BMI <25 kg/m2 (P values for interaction <0.05). We found an
      inverse association between prediagnostic sRAGE concentrations and risk of
      incident pancreatic cancer in postmenopausal women. A proinflammatory CBS was
      associated with increased risk only in women with normal BMI. MCP1 was not
      modulated by sRAGE.

PMID- 29573230
TI  - A case of endocervical minimal deviation adenocarcinoma with varicolored
      cytopathologic features on Pap smear.
AB  - We report a case of minimal deviation adenocarcinoma (MDA) of the uterine cervix
      showing varicolored cytopathologic features on Papanicolaou (Pap) smear, which
      may indicate features suggestive of lobular endocervical glandular hyperplasia
      (LEGH)-adenocarcinoma sequence. A 57-year-old woman presented with a profuse
      amount of watery vaginal discharge. Gynecological examination revealed a cervical
      mass with involvement of the right parametrium. Conventional Pap smear showed
      hypercellularity consisting of approximately 4 types of clusters as follows: (1)
      clusters showing a monolayered honeycomb sheet of endocervical cells with golden
      yellow mucin and bland nuclei, (2) three-dimensional clusters showing varicolored
      mucin and irregular nuclear overlapping, (3) irregularly shaped clusters showing
      distorted chicken-wire-mesh appearance with noticeable protrusions of the nuclei
      and clear or faint varicolored cytoplasm, and (4) crowded clusters showing scarce
      mucin and nuclear atypia. The surgically resected uterus revealed LEGH-mimicking
      lesion with fused papillae and a cribriform pattern in the endocervix and many
      glands exhibiting gastric differentiation that invaded deeper areas of the stroma
      with a subtle stromal reaction. Compared with histologic findings, two types of
      clusters, the crowded cluster with scarce mucin and the cluster with distorted
      chicken-wire-mesh-type appearance, were considered as adenocarcinoma, and the
      latter was interpreted as a gastric-type adenocarcinoma. Three-dimensional
      varicolored type clusters showed atypical features, but insufficient atypical
      features compared with those of adenocarcinoma. Detection of clusters with
      varicolored mucin on conventional Pap smear may provide a clue for the early
      recognition of the malignant potential of LEGH on cytology. The chicken-wire-mesh
      type clusters may be a characteristic cytologic finding of MDA.

PMID- 29573231
TI  - Caution with iceberg model for colonoscopy in mind! A large easily missed sessile
      serrated polyp surrounding seemingly diminutive protruded polyp: A case report.

PMID- 29573233
TI  - Adolescent preferences for weight terminology used by health care providers.
AB  - BACKGROUND: In light of high rates of obesity and weight stigma in youth, the
      American Academy of Paediatrics recommends that paediatric health care
      professionals use appropriate, sensitive and non-stigmatizing language in
      communication about weight with youth. For these efforts to be effective, there
      is a need to identify weight-based language preferences among youth with
      overweight and obesity, as research in this area is scarce. OBJECTIVES: The
      present study provides a systematic assessment of youth perspectives of weight
      based language used by providers. METHODS: Adolescents (ages 13-18 years; N =
      148) enrolled in a national weight loss camp were surveyed about their
      preferences for words that health providers use to refer to their body weight.
      Adolescents completed an online survey and responded to a list of 16 words
      describing excess body weight, as well as questions assessing demographics, body
      mass index, and experienced as well as internalized weight stigma. RESULTS:
      Adolescents assigned low ratings to words like 'fat', 'large', 'obese' and
      'extremely obese', indicating that they would not want providers to use these
      words when discussing their body weight. In contrast, words like 'weight
      problem', 'BMI' and 'plus size' were rated among the most preferred words for
      providers to use. Word preferences varied across gender, body mass index and
      extent of internalized weight stigma. CONCLUSIONS: These findings underscore the
      importance of acknowledging different word preferences among youth, and to avoid
      making assumptions about what words youth will feel most comfortable using in
      discussions about their body weight.

PMID- 29573232
TI  - Structural variations causing inherited peripheral neuropathies: A paradigm for
      understanding genomic organization, chromatin interactions, and gene
      dysregulation.
AB  - Inherited peripheral neuropathies (IPNs) are a clinically and genetically
      heterogeneous group of diseases affecting the motor and sensory peripheral
      nerves. IPNs have benefited from gene discovery and genetic diagnosis using next
      generation sequencing with over 80 causative genes available for testing. Despite
      this success, up to 50% of cases remain genetically unsolved. In the absence of
      protein coding mutations, noncoding DNA or structural variation (SV) mutations
      are a possible explanation. The most common IPN, Charcot-Marie-Tooth neuropathy
      type 1A (CMT1A), is caused by a 1.5 Mb duplication causing trisomy of the dosage
      sensitive gene PMP22. Using genome sequencing, we recently identified two large
      genomic rearrangements causing IPN subtypes X-linked CMT (CMTX3) and distal
      hereditary motor neuropathy (DHMN1), thereby expanding the spectrum of SV
      mutations causing IPN. Understanding how newly discovered SVs can cause IPN may
      serve as a useful paradigm to examine the role of topologically associated
      domains (TADs), chromatin interactions, and gene dysregulation in disease. This
      review will describe the growing role of SV in the pathogenesis of IPN and the
      importance of considering this type of mutation in Mendelian diseases where
      protein coding mutations cannot be identified.

PMID- 29573234
TI  - Modeling autism in non-human primates: Opportunities and challenges.
AB  - : Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized
      by social communication deficits and restricted, repetitive patterns of behavior.
      For more than a decade, genetically-modified, risk factor-induced, as well as
      naturally occurring rodent models for ASD have been used as the most predominant
      tools to dissect the molecular and circuitry mechanisms underlying ASD. However,
      the apparent evolutionary differences in terms of social behavior and brain
      anatomy between rodents and humans have become an issue of debate regarding the
      translational value of rodent models for studying ASD. More recently, genome
      manipulation of non human primates using lentivirus-based gene expression, TALEN
      and CRISPR/Cas9 mediated gene editing techniques, has been reported. Genetically
      modified non-human primate models for ASD have been produced and characterized.
      While the feasibility, value, and exciting opportunities provided by the non
      human primate models have been clearly demonstrated, many challenges still
      remain. Here, we review current progress, discuss the remaining challenges, and
      highlight the key issues in the development of non-human primate models for ASD
      research and drug development. Autism Res 2018, 11: 686-694. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      Over the last two decades, genetically modified rat and mouse models have been
      used as the most predominant tools to study mechanisms underlying autism spectrum
      disorder (ASD). However, the apparent evolutionary differences between rodents
      and humans limit the translational value of rodent models for studying ASD.
      Recently, several non-human primate models for ASD have been established and
      characterized. Here, we review current progress, discuss the challenges, and
      highlight the key issues in the development of non-human primate models for ASD
      research and drug development.

PMID- 29573235
TI  - Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of
      hepatocellular carcinoma.
AB  - Exosomal microRNAs have recently been studied as the potential diagnostic marker
      for various malignancies, including hepatocellular carcinoma (HCC). The aim of
      this study was to investigate serum exosomal microRNA profiles as HCC diagnostic
      marker. Transmission electron microscopy and Western blot were used to identify
      serum exosomes. Deep sequencing was performed to screen differentially expressed
      microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three
      upregulated and two downregulated microRNAs were selected for qPCR analysis. The
      levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39
      microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 was
      further analyzed and significantly higher in HCC than LC and normal control (NC)
      groups (P < 0.001), but not different from chronic hepatitis group (P > 0.05).
      The receiver operating characteristic curve was used to evaluate the diagnostic
      performance of candidate microRNAs. Area under the curve (AUC) of miR-148a was
      0.891 [95% confidence interval (CI), 0.809-0.947] in discriminating HCC from LC,
      remarkably higher than alpha-fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607-0.803).
      Binary logistic regression was adopted to establish the diagnostic model for
      discriminating HCC from LC. And the combination of miR-122, miR-148a, and AFP
      increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for
      distinguishing early HCC from LC. miR-122 was the best for differentiating HCC
      from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggest that serum exosomal
      microRNAs signature or their combination with traditional biomarker may be used
      as a suitable peripheral screening tool for HCC.

PMID- 29573236
TI  - Efficacy, safety and predictive indicators of apatinib after multilines treatment
      in advanced nonsquamous nonsmall cell lung cancer: Apatinib treatment in
      nonsquamous NSCLC.
AB  - AIM: Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who
      experienced progression with two or more lines chemotherapy have no treatment
      options that clearly confer a survival benefit. As a novel vascular endothelial
      growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain
      antitumor effect for various solid tumors. The present study evaluated the
      efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage
      treatment in Chinese real-world practice. METHODS: Twenty-eight patients were
      enrolled in this observational study from October 2015 to May 2017. Progression
      free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve
      and intergroup comparisons were carried out by log-rank test. Objective response
      rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also
      evaluated. RESULTS: Seven patients obtained partial response, and 18 obtained
      stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS
      were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months,
      respectively. The efficacy analysis showed that Eastern Cooperative Oncology
      Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P <
      0.05), and hypertension during apatinib treatment was correlated with prolonged
      OS (P < 0.05). Cox regression showed that ECOG performance status (P < 0.01) (RR
      = 0.231) (95% CI 0.083-0.642) and hypertension during apatinib treatment (P =
      0.05) were predictive indicators for apatinib treatment. Grade 3-4 AEs with
      incidences of 10% or greater were hypertension (21%), hand-foot syndrome (14%)
      and proteinuria (11%) which could be relieved by dose reduction. CONCLUSION: In
      conclusion, apatinib has a certain therapeutic effect in patients with advanced
      nonsquamous NSCLC. ECOG performance status and hypertension during apatinib might
      be predictive indicators for treatment efficacy.

PMID- 29573237
TI  - Vitamin D administration leads to a shift of the intestinal bacterial composition
      in Crohn's disease patients, but not in healthy controls.
AB  - OBJECTIVE: Dysbiosis is a common feature in the pathogenesis of inflammatory
      bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem
      to play a role in the intestinal inflammation of IBD. The aim of this study was
      to investigate whether vitamin D administration has an impact on the bacterial
      composition in Crohn's disease (CD) compared to healthy controls (HC). METHODS: A
      prospective, longitudinal, controlled interventional analysis was conducted in
      seven patients with CD in clinical remission and 10 HC to investigate the effect
      of orally administrated vitamin D on the intestinal bacterial composition using
      16S ribosomal RNA gene amplicon sequencing. Clinical parameters were assessed.
      RESULTS: In contrast to HC, microbial communities of CD patients changed
      significantly during early vitamin D administration. However, a further increase
      in vitamin D level was associated with a reversal of this effect and additionally
      with a decrease in the bacterial richness in the CD microbiome. Specific species
      with a high abundancy were found during vitamin D administration in CD, but not
      in HC; the abundancy of Alistipes, Barnesiella, unclassified Porphyromonadaceae
      (both Actinobacteria), Roseburia, Anaerotruncus, Subdoligranulum and an
      unclassified Ruminococaceae (all Firmicutes) increased significantly after 1-week
      vitamin D administration in CD. CONCLUSIONS: Vitamin D has a specific influence
      on the bacterial communities in CD, but not in HC. Administration of vitamin D
      may have a positive effect in CD by modulating the intestinal bacterial
      composition and also by increasing the abundance of potential beneficial
      bacterial strains.

PMID- 29573238
TI  - Trabecular Anisotropy in the Primate Mandibular Condyle Is Associated with
      Dietary Toughness.
AB  - Past attempts to establish a relationship between mandibular morphology and
      different dietary categories (e.g., frugivore, folivore, insectivore) have had
      mixed results, possibly because descriptive dietary categories are too broad and
      obscure variation within primate diets. Another potential reason is that not all
      aspects of skeletal architecture, especially trabecular anisotropy, have factored
      into functional assessments of dietary inputs into jaw form. Recent emphasis on
      quantifying food mechanical properties (FMPs) has provided an alternative to
      reliance on dietary categories. We used data on FMPs to test for correlations
      among dietary toughness and Young's modulus and the trabecular structure of the
      mandibular condyle, which is loaded during feeding and should reflect differences
      in masticatory stresses associated with different dietary FMPs. Adult primate
      mandibles from 11 species were imaged using high-resolution X-ray computed
      tomography, and trabecular structure was analyzed with BoneJ and Quant3D to
      assess common three-dimensional trabecular parameters. Results of phylogenetic
      generalized least squares analysis suggested a positive correlation between the
      degree of anisotropy (DA) and toughness, and weaker correlations between FMPs and
      various other trabecular variables. Because the DA contributes to the mechanical
      properties of bone, these results suggest a functional relationship between
      dietary toughness and trabecular anisotropy in the mandibular condyle. Such a
      perspective underscores the need to consider all aspects of skeletal morphology
      in evaluating the links between diet and jaw biomechanics. Anat Rec, 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 29573239
TI  - Thresholds of physical activity associated with obesity by level of sedentary
      behaviour in children.
AB  - BACKGROUND: It is unknown whether moderate-to-vigorous physical activity (MVPA)
      thresholds for obesity should be adapted depending on level of sedentary
      behaviour in children. OBJECTIVE: The objective of the study is to determine the
      MVPA thresholds that best discriminate between obese and non-obese children, by
      level of screen time and total sedentary time in 12 countries. METHODS: This
      multinational, cross-sectional study included 6522 children 9-11 years of age.
      MVPA and sedentary time were assessed using waist-worn accelerometry, while
      screen time was self-reported. Obesity was defined according to the World Health
      Organization reference data. RESULTS: Receiver operating characteristic curve
      analyses showed that the best thresholds of MVPA to predict obesity ranged from
      53.8 to 73.9 min d-1 in boys and from 41.7 to 58.7 min d-1 in girls, depending on
      the level of screen time. The MVPA cut-offs to predict obesity ranged from 37.9
      to 75.9 min d-1 in boys and from 32.5 to 62.7 min d-1 in girls, depending on the
      level of sedentary behaviour. The areas under the curve ranged from 0.57 to 0.73
      ('fail' to 'fair' accuracy), and most sensitivity and specificity values were
      below 85%, similar to MVPA alone. Country-specific analyses provided similar
      findings. CONCLUSIONS: The addition of sedentary behaviour levels to MVPA did not
      result in a better predictive ability to classify children as obese/non-obese
      compared with MVPA alone.

PMID- 29573240
TI  - Liquid biopsy by NGS: differential presence of exons (DPE) in cell-free DNA
      reveals different patterns in metastatic and nonmetastatic colorectal cancer.
AB  - Next-generation sequencing (NGS) has been proposed as a suitable tool for liquid
      biopsy in colorectal cancer (CRC), although most studies to date have focused
      almost exclusively on sequencing of panels of potential clinically actionable
      genes. We evaluated the clinical value of whole-exome sequencing (WES) of cell
      free DNA (cfDNA) circulating in plasma, with the goal of identifying differential
      clinical profiles in patients with CRC. To this end, we applied an original
      concept, "differential presence of exons" (DPE). We determined differences in
      levels of 379 exons in plasma cfDNA and used DPE analysis to cluster and classify
      patients with disseminated and localized disease. The resultant bioinformatics
      analysis pipeline allowed us to design a predictive DPE algorithm in a small
      subset of patients that could not be initially classified based on the selection
      criteria. This DPE suggests that these nucleic acids could be actively released
      by both tumor and nontumor cells as a means of intercellular communication and
      might thus play a role in the process of malignant transformation. DPE is a new
      technique for the study of plasma cfDNA by WES that might have predictive and
      prognostic value in patients with CRC.

PMID- 29573241
TI  - Large buoyant particles dominated by cyanobacterial colonies harbor distinct
      bacterial communities from small suspended particles and free-living bacteria in
      the water column.
AB  - Worldwide cyanobacterial blooms greatly impair ecosystems in many eutrophic lakes
      and impact the microbial environment. In particular, large cyanobacterial
      colonies that are buoyant on the water surface may provide a distinct habitat for
      bacteria from other small particles that are suspended stably in the water
      column. To test this hypothesis, bacterial communities (excluding cyanobacteria)
      attached to large particles dominated by cyanobacterial colonies (>120 MUm, LA),
      small particles (3-36 MUm, SA), and free-living bacteria (0.2-3 MUm, FL) were
      investigated monthly for a year in Lake Taihu, China. Results confirmed that the
      Shannon diversity index of LA was significantly lower than that of FL, which was
      lower than that of SA. Cytophagia and Alphaproteobacteria were specially enriched
      in LA. Although samples in each habitat collected during high- (May to November)
      and low-bloom seasons (December to April) were separated, all samples in LA were
      clustered and separated from SA and FL, which were also clustered during the same
      sampling seasons. In addition, the bacterial communities in LA were correlated
      with nitrate level, whereas FL and SA were correlated with nitrate level and
      temperature. Mantel analysis revealed that bacterial composition significantly
      correlated with the cyanobacterial composition in LA and FL but not in SA. These
      results indicate that LA provides distinct niches to bacteria, whereas the
      differentiation of bacterial communities in FL and SA is seasonally dependent.

PMID- 29573242
TI  - Associations of neonatal adiponectin and leptin with growth and body composition
      in African American infants.
AB  - BACKGROUND: Cord blood adiponectin and leptin concentrations are associated with
      birth weight and adiposity. Birth size and rate of infant weight gain are
      associated with future obesity risk. However, it is unclear whether biomarkers
      reflecting the intrauterine environment are predictive of infant prospective body
      composition change. OBJECTIVES: To examine whether cord blood adiponectin and
      leptin are predictive of neonatal adiposity and fat mass (FM) accrual to 3 months
      of age. METHODS: Participants (n = 36) were healthy African American infants.
      Leptin and adiponectin concentrations were measured in umbilical cord blood. At 2
      weeks and 3 months, infant body composition was assessed via air displacement
      plethysmography. Weight-for-length z-scores (WLZ) were calculated using World
      Health Organization standards. Multiple linear regression was used to examine
      associations of cord blood adiponectin and leptin with birth WLZ; WLZ, FM and fat
      free mass at 2 weeks, and the conditional change in these variables from 2 weeks
      to 3 months (body composition at 3 months adjusted for body composition at 2
      weeks). RESULTS: Adiponectin was positively associated with FM at 2 weeks (r =
      0.45, P < 0.01), but inversely associated with conditional FM change from 2 weeks
      to 3 months of age (r = -0.38, P < 0.05). Leptin was not significantly associated
      with infant body composition. CONCLUSIONS: Adiponectin may be a marker for FM
      accrual in African American infants, a relatively understudied population with a
      high long-term obesity risk. Mechanistic studies are needed to determine whether
      adiponectin directly influences infant growth or is simply a maker reflective of
      other ongoing biological changes after birth.

PMID- 29573243
TI  - lncRNA-NKILA/NF-kappaB feedback loop modulates laryngeal cancer cell
      proliferation, invasion, and radioresistance.
AB  - Laryngeal cancer is one of the most common head and neck malignant tumors and is
      commonly resistant to X-ray-based radiotherapy. NF-kappaB interacting lncRNA
      (NKILA) has been reported to serve as a tumor suppressor in several cancers
      through combining with NF-kappaB: IkappaB complex thereby inhibiting NF-kappaB
      activation. Herein, we demonstrated a low NKILA expression in laryngeal cancer
      and its correlation with shorter overall survival in patients with laryngeal
      cancer. NKILA serves as a tumor suppressor in laryngeal cancer by suppressing
      laryngeal cancer cell viability and migration, whereas promoting cell apoptosis;
      NKILA knockdown reverses the cytotoxicity of X-ray radiation on laryngeal cancer
      cells through combining with NF-kappaB: IkappaB complex to inhibit IkappaB
      phosphorylation, inhibit p65 nuclear translocation, and finally inhibit NF-kappaB
      activation. NF-kappaB binds to the promoter region of NKILA to activate its
      transcriptional activity, upregulated NKILA then inhibits IkappaB phosphorylation
      and NF-kappaB activation, thus forming a negative feedback loop to sensitize
      laryngeal cancer cell to X-ray radiation. In conclusion, NKILA can serve as a
      promising agent of enhancing the cytotoxicity of X-ray radiation on laryngeal
      cancer and addressing the radioresistance of laryngeal cancer.

PMID- 29573244
TI  - Dynamics of coral-associated microbiomes during a thermal bleaching event.
AB  - Coral-associated microorganisms play an important role in their host fitness and
      survival. A number of studies have demonstrated connections between thermal
      tolerance in corals and the type/relative abundance of Symbiodinium they harbor.
      More recently, the shifts in coral-associated bacterial profiles were also shown
      to be linked to the patterns of coral heat tolerance. Here, we investigated the
      dynamics of Porites lutea-associated bacterial and algal communities throughout a
      natural bleaching event, using full-length 16S rRNA and internal transcribed
      spacer sequences (ITS) obtained from PacBio circular consensus sequencing. We
      provided evidence of significant changes in the structure and diversity of coral
      associated microbiomes during thermal stress. The balance of the symbiosis
      shifted from a predominant association between corals and Gammaproteobacteria to
      a predominance of Alphaproteobacteria and to a lesser extent Betaproteobacteria
      following the bleaching event. On the contrary, the composition and diversity of
      Symbiodinium communities remained unaltered throughout the bleaching event. It
      appears that the switching and/or shuffling of Symbiodinium types may not be the
      primary mechanism used by P. lutea to cope with increasing seawater temperature.
      The shifts in the structure and diversity of associated bacterial communities may
      contribute more to the survival of the coral holobiont under heat stress.

PMID- 29573245
TI  - Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common
      Homozygous SLC4A1 Mutation in Two Lao Families.
AB  - Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1
      gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows
      marked difference in inheritance patterns and clinical features in different
      parts of the world. While the disease shows autosomal dominant inheritance
      without any red cell morphological abnormalities in the temperate countries, it
      is almost invariably recessive, and often accompanies red cell morphological
      abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia.
      Here, we report three patients with autosomal recessive (AR) dRTA, presenting
      with typical findings of failure to thrive and rickets, from two unrelated Lao
      families. The mutational analyses revealed that all three patients harbored the
      same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali
      and potassium resulted in remarkable improvement of growth retardation and
      skeletal deformities of the patients. This is the first case report of Lao
      patients with AR dRTA caused by SLC4A1 mutations.

PMID- 29573246
TI  - Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early
      Parkinson's Disease: a Quantitative Susceptibility Mapping Study.
AB  - BACKGROUND: Quantitative susceptibility mapping (QSM) has been used to measure
      iron accumulation in the deep nuclei of patients with Parkinson's disease (PD).
      This study examined the relationship between non-motor symptoms (NMSs) and iron
      accumulation in the deep nuclei of patients with PD. METHODS: The QSM data were
      acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early
      PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used
      for evaluation of NMSs in patients. The patients were divided into high NMS and
      low NMS groups. The region-of-interest analyses were performed in the following
      deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars
      reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate
      nucleus. RESULTS: Thirteen patients had high NMS scores (total K-NMSS score, mean
      = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not
      different among the patients with high NMS scores, low NMS scores, and controls.
      The QSM values were not correlated linearly with K-NMSS total score after
      adjusting the age at acquisition of brain MRI. CONCLUSION: The study demonstrated
      that the NMS burdens are not associated with iron accumulation in the deep nuclei
      of patients with PD. These results suggest that future neuroimaging studies on
      the pathology of NMSs in PD should use more specific and detailed clinical tools
      and recruit PD patients with severe NMSs.

PMID- 29573247
TI  - Safety and Immunogenicity of an Egg-Cultivated Quadrivalent Inactivated Split
      virion Influenza Vaccine (GC3110A) in Healthy Korean Children: a Randomized,
      Double-blinded, Active-controlled Phase III Study.
AB  - BACKGROUND: The frequency with which the 2 B lineages have been found to
      cocirculate in a season has been on the rise, which has spurred the need for a
      quadrivalent influenza vaccine (QIV) to protect against both B lineages. The
      World Health Organization (WHO) recommended that QIV include both B lineages
      beginning in the 2013-2014 flu season. This study was conducted to evaluate the
      immunogenicity and safety of an egg-cultivated QIV in healthy Korean children and
      adolescents aged >= 6 months to < 19 years. METHODS: A total of 528 subjects were
      randomized 4:1 to receive either a QIV (GC3110A) or a trivalent influenza
      vaccine. Hemagglutination inhibition antibody responses were assessed 28 days
      after the last dose. Safety was also evaluated. RESULTS: The proportion of
      subjects in the GC3110A group who achieved seroconversion was confirmed to exceed
      40% across all age groups. The proportion of subjects aged >= 6 months to < 3
      years in the GC3110A group who achieved seroprotection failed to meet the
      Ministry of Food and Drug Safety (MFDS) standard of 70%. Potential causes may
      include the small number of subjects, as well as the small dosage. However,
      results pertaining to the other age groups satisfied the MFDS standard. The
      safety profile was also comparable to that of the control. CONCLUSION: The new
      quadrivalent split influenza vaccine may offer broader protection to children and
      adolescents aged >= 3 years to < 19 years of age against both influenza B
      lineages than the existing trivalent influenza vaccines (Registered at the
      ClinicalTrials.gov NCT02541253).

PMID- 29573248
TI  - Comparison between Newly Developed and Commercial Inhalant Skin Prick Test
      Reagents Using In Vivo and In Vitro Methods.
AB  - BACKGROUND: We developed skin prick test (SPT) reagents for common inhalant
      allergens that reflected the real exposure in Korea. The study aim was to
      evaluate diagnostic usefulness and allergen potency of our inhalant SPT reagents
      in comparison with commercial products. METHODS: We produced eight common
      inhalant allergen SPT reagents using total extract (Prolagen): Dermatophagoides
      farinae, Dermatophagoides pteronyssinus, oak, ragweed, mugwort, Humulus japonicus
      pollens, as well as cat and dog allergens. We compared the newly developed
      reagents with three commercially available SPT reagents (Allergopharma, Hollister
      Stier, Lofarma). We measured total protein concentrations, sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), major allergen
      concentration, and biological allergen potencies measured by immunoglobulin E
      (IgE) immunoblotting and ImmunoCAP inhibition test. RESULTS: Diagnostic values of
      these SPT reagents were expressed as positivity rate and concordance rate of the
      results from ImmunoCAP allergen-specific IgE test in 94 allergic patients. In
      vitro analysis showed marked differences in protein concentrations, SDS-PAGE
      features, major allergen concentrations, and biological allergen potencies of
      four different SPT reagents. In vivo analysis showed that positive rates and
      concordance rates of Prolagen(r) SPT reagents were similar compared to the three
      commercial SPT reagents. CONCLUSION: The newly developed Prolagen(r) inhalant SPT
      reagents are not inferior to the commercially available SPT reagents in allergy
      diagnosis.

PMID- 29573250
TI  - Will a Quadrivalent Vaccine Solve the Problem of Influenza B Mismatches?

PMID- 29573249
TI  - The Risk of Spontaneous Preterm Birth according to Maternal Pre-pregnancy Body
      Mass Index in Twin Gestations.
AB  - BACKGROUND: Maternal obesity is a well-known risk factor for both total preterm
      birth (PTB) and spontaneous PTB in singleton gestation, whereas this association
      is not well determined in multiple pregnancy. The objective of this study was to
      determine the risk of spontaneous PTB according to the pre-pregnancy body mass
      index (BMI) in twin gestations. METHODS: The association between the risk of PTB
      and pre-pregnancy BMI was determined in women pregnant with twins between 2004
      and 2014. Pre-pregnancy BMI values were divided into three groups
      (underweight/normal/overweight and obese). PTB was classified as spontaneous PTB
      (following preterm premature rupture of membranes, preterm labor, or cervical
      insufficiency) or medically indicated PTB (cesarean section or induction of labor
      because of maternal/fetal indications). RESULTS: A total of 1,959 women were
      included in the analysis, and the percentages of total PTB and spontaneous PTB
      were 13.1% and 9.3%. The percentages of total PTB and spontaneous PTB in three
      groups were 14.1%, 11.9%, 16.3%, respectively, and 11.0%, 8.0%, 12.5% (P < 0.05
      between normal and overweight/obese women). The risks of total and spontaneous
      PTB in overweight/obese women were higher than those in women with normal weight,
      even after adjustment for prior history of PTB, age, maternal height, parity, in
      vitro fertilization-embryo transfer (IVF-ET) (odds ratio [OR], 1.43; 95%
      confidence interval [CI], 1.01-2.03; OR, 1.58; 95% CI, 1.05-2.36). CONCLUSION:
      The risks of both total and spontaneous PTB were significantly greater in the
      overweight/obese group than in the normal BMI group.

PMID- 29573251
TI  - Inappropriate Authorship and Kinship in Research Evaluation.

PMID- 29573254
TI  - Optical model of the murine lung to optimize pulmonary illumination.
AB  - We describe a Monte Carlo model of the mouse torso to optimize illumination of
      the mouse lung for fluorescence detection of low levels of pulmonary pathogens,
      specifically Mycobacterium tuberculosis. After validation of the simulation with
      an internally illuminated optical phantom, the entire mouse torso was simulated
      to compare external and internal illumination techniques. Measured optical
      properties of deflated mouse lungs were scaled to mimic the diffusive properties
      of inflated lungs in vivo. Using the full-torso model, a 2  *   to 3  *  
      improvement in average fluence rate in the lung was seen for dorsal compared with
      ventral positioning of the mouse with external illumination. The enhancement in
      average fluence rate in the lung using internal excitation was 40  *   to 60  *  
      over external illumination in the dorsal position. Parameters of the internal
      fiber optic source were manipulated in the model to guide optimization of the
      physical system and experimental protocol for internal illumination and whole
      body detection of fluorescent mycobacteria in a mouse model of infection.

PMID- 29573252
TI  - Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.
AB  - BACKGROUND: The aggravating factors still remained unclear in inflammatory bowel
      disease (IBD). Despite many different therapeutic approaches, many patients do
      not respond to the therapy. The anti-inflammatory effect of insulin-like growth
      factor-binding protein-3 (IGFBP-3) was suggested because of its capability of
      nuclear factor-kappaB (NF-kappaB) signaling inhibition. Therefore, we
      hypothesized that the up-regulation of IGFBP-3 would inhibit an inflammatory
      process. METHODS: Lipopolysaccharides (LPS) treated intestinal epithelial cell 6
      (IEC-6) and dextran sodium sulfate (DSS) induced colitis mice were used as
      colitis models. Exogenous IGFBP-3 expression was accomplished using the
      adenoviral vector system expressing IGFBP-3 (Ad/IGFBP-3). The inflammatory
      responses and relevant cellular responses in IEC-6 cells influenced by IGFBP-3
      expression were evaluated by western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, and reactive oxygen species (ROS)
      measurement. The severity of colitis was evaluated with the colon tissues of DSS
      induced mouse model. RESULTS: We found that the IGFBP-3 expression reduced the
      production of inflammatory cytokines (cyclooxygenase-2, interleukin-1beta, tumor
      necrosis factor-alpha) and ROS formation. IGFBP-3 expression also induced cell
      viability and inhibited NF-kappaB activation. In line with this data, the
      severity of DSS-induced mouse colitis was greatly ameliorated by the treatment of
      IGFBP-3 expressing adenoviral particles characterized with less weight loss and
      preserved colon length compared with the mice treated with DSS alone. The
      histopathology of the colon showed the reducing signs of colitis in Ad/IGFBP-3
      treated DSS-mice group. CONCLUSION: Therefore, our data suggest that Ad/IGFBP-3
      up-regulation reduces colonic inflammatory response as a novel therapeutic
      protocol for IBD.

PMID- 29573255
TI  - Internal-illumination photoacoustic computed tomography.
AB  - We report a photoacoustic computed tomography (PACT) system using a customized
      optical fiber with a cylindrical diffuser to internally illuminate deep targets.
      The traditional external light illumination in PACT usually limits the
      penetration depth to a few centimeters from the tissue surface, mainly due to
      strong optical attenuation along the light propagation path from the outside in.
      By contrast, internal light illumination, with external ultrasound detection, can
      potentially detect much deeper targets. Different from previous internal
      illumination PACT implementations using forward-looking optical fibers, our
      internal-illumination PACT system uses a customized optical fiber with a 3-cm
      long conoid needle diffuser attached to the fiber tip, which can homogeneously
      illuminate the surrounding space and substantially enlarge the field of view. We
      characterized the internal illumination distribution and PACT system performance.
      We performed tissue phantom and in vivo animal studies to further demonstrate the
      superior imaging depth using internal illumination over external illumination. We
      imaged a 7.5-cm-deep leaf target embedded in optically scattering medium and the
      beating heart of a mouse overlaid with 3.7-cm-thick chicken tissue. Our results
      have collectively demonstrated that the internal light illumination combined with
      external ultrasound detection might be a useful strategy to improve the
      penetration depth of PACT in imaging deep organs of large animals and humans.

PMID- 29573257
TI  - Bacterial Iron Homeostasis Regulation by sRNAs.
AB  - While iron is essential to sustain growth, its excess can be detrimental to the
      cell by generating highly toxic reactive oxygen species. Regulation of iron
      homeostasis thus plays a vital role in almost all living organisms. During the
      last 15 years, the small RNA (sRNA) RyhB has been shown to be a key actor of iron
      homeostasis regulation in bacteria. Through multiple molecular mechanisms, RyhB
      represses expendable iron-utilizing proteins, promotes siderophore production,
      and coordinates Fe-S cluster cofactor biogenesis, thereby establishing a so
      called iron-sparing response. In this review, we will summarize knowledge on how
      sRNAs control iron homeostasis mainly through studies on RyhB in Escherichia
      coli. The parallel roles and modes of action of other sRNAs in different bacteria
      will also be described. Finally, we will discuss what questions remain to be
      answered concerning this important stress response regulation by sRNAs.

PMID- 29573258
TI  - Carbohydrate Utilization in Bacteria: Making the Most Out of Sugars with the Help
      of Small Regulatory RNAs.
AB  - Survival of bacteria in ever-changing habitats with fluctuating nutrient supplies
      requires rapid adaptation of their metabolic capabilities. To this end,
      carbohydrate metabolism is governed by complex regulatory networks including
      posttranscriptional mechanisms that involve small regulatory RNAs (sRNAs) and RNA
      binding proteins. sRNAs limit the response to substrate availability and set the
      threshold or time required for induction and repression of carbohydrate
      utilization systems. Carbon catabolite repression (CCR) also involves sRNAs. In
      Enterobacteriaceae, sRNA Spot 42 cooperates with the transcriptional regulator
      cyclic AMP (cAMP)-receptor protein (CRP) to repress secondary carbohydrate
      utilization genes when a preferred sugar is consumed. In pseudomonads, CCR
      operates entirely at the posttranscriptional level, involving RNA-binding protein
      Hfq and decoy sRNA CrcZ. Moreover, sRNAs coordinate fluxes through central
      carbohydrate metabolic pathways with carbohydrate availability. In Gram-negative
      bacteria, the interplay between RNA-binding protein CsrA and its cognate sRNAs
      regulates glycolysis and gluconeogenesis in response to signals derived from
      metabolism. Spot 42 and cAMP-CRP jointly downregulate tricarboxylic acid cycle
      activity when glycolytic carbon sources are ample. In addition, bacteria use
      sRNAs to reprogram carbohydrate metabolism in response to anaerobiosis and iron
      limitation. Finally, sRNAs also provide homeostasis of essential anabolic
      pathways, as exemplified by the hexosamine pathway providing cell envelope
      precursors. In this review, we discuss the manifold roles of bacterial sRNAs in
      regulation of carbon source uptake and utilization, substrate prioritization, and
      metabolism.

PMID- 29573256
TI  - Global Regulation by CsrA and Its RNA Antagonists.
AB  - The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in
      the posttranscriptional regulation of gene expression. Its binding interactions
      with RNA have been documented at atomic resolution and shown to alter RNA
      secondary structure, RNA stability, translation, and/or Rho-mediated
      transcription termination through a growing number of molecular mechanisms. In
      Gammaproteobacteria, small regulatory RNAs (sRNAs) that contain multiple CsrA
      binding sites compete with mRNA for binding to CsrA, thereby sequestering and
      antagonizing this protein. Both the synthesis and turnover of these sRNAs are
      regulated, allowing CsrA activity to be rapidly and efficiently adjusted in
      response to nutritional conditions and stresses. Feedback loops between the Csr
      regulatory components improve the dynamics of signal response by the Csr system.
      The Csr system of Escherichia coli is intimately interconnected with other global
      regulatory systems, permitting it to contribute to regulation by those systems.
      In some species, a protein antagonist of CsrA functions as part of a checkpoint
      for flagellum biosynthesis. In other species, a protein antagonist participates
      in a mechanism in which a type III secretion system is used for sensing
      interactions with host cells. Recent transcriptomics studies reveal vast effects
      of CsrA on gene expression through direct binding to hundreds of mRNAs, and
      indirectly through its effects on the expression of dozens of transcription
      factors. CsrA binding to base-pairing sRNAs and novel mRNA segments, such as the
      3' untranslated region and deep within coding regions, predict its participation
      in yet-to-be-discovered regulatory mechanisms.

PMID- 29573259
TI  - Transmission, Human Population, and Pathogenicity: the Ebola Case in Point.
AB  - The 2013-2016 Ebola outbreak in West Africa has been the largest ever of a known
      disease in a new context that produced an unprecedented impact and is changing
      the international approach to responding to public health emergencies. The
      unprecedented scale of the outbreak, the use of advanced technology for detecting
      and characterizing the infectious agent, along with the opportunity to treat
      patients in modern facilities have greatly increased our knowledge of the disease
      and its transmission. Also, for the first time, an important international effort
      has been deployed to control the spread of the epidemic by providing care to
      patients and by adopting basic measures of public health control. Apart from
      supportive treatment and intensive therapy with fluids and electrolytes, no new
      compounds have been proved to be clinically effective to treat Ebola virus
      disease; however, a specific vaccine has shown significant protection in clinical
      trials in Guinea, opening an expectation for controlling future outbreaks.

PMID- 29573260
TI  - Correcting for prematurity with the Bayley Scales of Infant Development.

PMID- 29573261
TI  - Development of novel monoclonal antibodies to dog leukocyte antigen DR displaying
      direct and immune-mediated cytotoxicity toward canine lymphoma cell lines.
AB  - Spontaneous canine lymphoma (CL) has become a promising, nonrodent model for
      advancing the therapeutic strategies of human hematological malignancies. As new
      resources for veterinary and comparative studies on CL-associated antigens, we
      developed 2 novel mouse monoclonal antibodies, denoted B5 and E11, that
      recognized the canine major histocompatibility Class II DR antigens (dog
      leukocyte antigen DR). Using flow cytometry and solid phase immunoenzymatic
      assays, we showed that the antigens recognized by B5 and E11 were strongly
      expressed in several CL cell lines and the ex vivo canine neoplastic cells of B
      and mixed B/T immunophenotypes. Additionally, we evaluated a minimal cross
      reactivity of B5 and E11 with the human B-cell line, Raji. By the ectopic
      expression of the hybrid murine/canine I-E/DR dimers in the HEK293 cells, we
      demonstrated that the epitope of B5 was localized to the invariant DRalpha chain,
      whereas the epitope of E11 was collectively formed by the DRalpha and DRbeta
      chains. Both epitopes were conformational and conserved in all the tested
      unrelated individuals of different dog breeds. In vitro treatment of 2 CL B-cell
      lines (CLBL1 and CLB70) with B5 and E11 rapidly induced a direct apoptotic cell
      death. Similarily, both mouse monoclonal antibodies efficiently killed the above
      cell lines through the mechanisms of complement-dependent and antibody-mediated
      cellular phagocytosis. Collectively, our data support the further development of
      B5 and E11 as novel tools for dog leukocyte antigen DR-targeted, preclinical
      trials involving CL.

PMID- 29573262
TI  - Effect of Bronsted acidic ionic liquid 1-(1-propylsulfonic)-3-methylimidazolium
      chloride on growth and co-fermentation of glucose, xylose and arabinose by
      Zymomonas mobilis AX101.
AB  - : The potential of large-scale lignocellulosic biomass hydrolysis to fermentable
      sugars using ionic liquids has increased interest in this green chemistry route
      to fermentation for fuel-ethanol production. The ionic liquid 1-(1
      propylsulfonic)-3-methylimidazolium chloride compared to other reported ionic
      liquids has the advantage of hydrolysing lignocellulosic biomass to reducing
      sugars at catalytic concentrations (<=0.032 mol l-1 ) in a single step. However,
      effects of this ionic liquid on co-fermentation of glucose, xylose and arabinose
      to ethanol by recombinant Zymomonas mobilisAX101 has not been studied. Authentic
      glucose, xylose and arabinose were used to formulate fermentation media at
      varying catalytic 1-(1-propylsulfonic)-3-methylimidazolium chloride
      concentrations for batch co-fermentation of the sugars using Z. mobilisAX101. The
      results showed that at 0.008, 0.016 and 0.032 mol l-1 ionic liquid in the culture
      medium, cell growth decreased by 10, 27 and 67% respectively compared to the
      control. Ethanol yields were 62.6, 61.8, 50.5 and 23.1% for the control, 0.008,
      0.016 and 0.032 mol l-1 ionic liquid respectively. The results indicate that
      lignocellulosic biomass hydrolysed using 0.008 mol l-1 of 1-(1-propylsulfonic)-3
      methylimidazolium chloride would eliminate an additional separation step and
      provide a ready to use fermentation substrate. SIGNIFICANCE AND IMPACT OF STUDY:
      This is the first reported study of the effect of the Bronsted acidic ionic
      liquid 1-(1-propylsulfonic)-3-methylimidazolium chloride on growth and co
      fermentation of glucose, xylose and arabinose by Zymomonas mobilisAX101 in batch
      culture. Growth on and co-fermentation of the sugars by Z. mobilisAX 101 with no
      significant inhibition by the ionic liquid at the same catalytic amounts of 0.008
      mol l-1 used to hydrolyse lignocellulosic biomass to reducing sugars overcome two
      major hurdles that adversely affect the process economics of large-scale
      industrial cellulosic fuel ethanol production; the energy-intensive hydrolysis
      and ionic liquid separation steps.

PMID- 29573263
TI  - Effect of pre-operative methylprednisolone on orthostatic hypotension during
      early mobilization after total hip arthroplasty.
AB  - BACKGROUND: Orthostatic hypotension (OH) and intolerance (OI) are common after
      total hip arthroplasty (THA) and may delay early mobilization. The pathology of
      OH and OI includes a dysregulated post-operative vasopressor response, by a
      hitherto unknown mechanism. We hypothesized that OI could be related to the
      inflammatory stress response which is inhibited by steroid administration.
      Consequently, this study evaluated the effect of a pre-operative high-dose
      methylprednisolone on OH and OI early after THA. METHODS: Randomized, double
      blind, placebo-controlled study in 59 patients undergoing elective unilateral THA
      with spinal anesthesia and a standardized multimodal analgesic regime. Patients
      were allocated (1 : 1) to pre-operative intravenous (IV) methylprednisolone (MP)
      125 mg or isotonic saline (C). OH, OI and cardiovascular responses to sitting and
      standing were evaluated using a standardized mobilization protocol pre
      operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure
      and heart rate were measured non-invasively (Nexfin(r) ). The systemic
      inflammation was monitored by the C-reactive protein (CRP) response. RESULTS: At
      6 h post-operatively, 11 (38%) versus 11 (37%) patients had OH in group MP and
      group C, respectively (RR 1.02 (0.60 to 1.75; P = 1.00)), whereas OI was present
      in 9 (31%) versus 13 (43%) patients (RR 0.76 (0.42 to 1.36; P = 0.42)),
      respectively. At 24 h post-operatively, the prevalence of OH and OI did not
      differ between groups, though CRP levels were significantly reduced in group MP
      (P < 0.001). CONCLUSION: Pre-operative administration of 125 mg
      methylprednisolone IV did not reduce OH or OI compared with placebo despite a
      reduced inflammatory response.

PMID- 29573264
TI  - Age-related differences in sequence learning: Findings from two visuo-motor
      sequence learning tasks.
AB  - The Serial Reaction Time Task (SRTT) is thought to assess implicit learning,
      which seems to be preserved with age. However, the reaction time (RT) measures
      employed on implicit-like tasks might be too unreliable to detect individual
      differences. We investigated whether RT-based measures mask age effects by
      comparing the performance of 43 younger and 35 older adults on SRTT and an
      explicit-like Predictive Sequence Learning Task (PSLT). RT-based measures
      (difference scores and a ratio) were collected for both tasks, and accuracy was
      additionally measured for PSLT. We also measured fluid abilities. The RT
      difference scores indicated preserved SRTT and PSLT performance with age and did
      not correlate with fluid abilities, while ratio RT and the accuracy-based
      measures indicated age-related decline and correlated with fluid abilities.
      Therefore, RT-difference scores might mask individual differences, which
      compromises the interpretation of previous studies using SRTT.

PMID- 29573265
TI  - Hypohidrotic ectodermal dysplasia with strabismus.

PMID- 29573266
TI  - Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK
      cells during expansion and thereby enhances effector functions in a dose- and
      time-dependent manner.
AB  - Natural killer (NK) cells play a major role in host immunity against leukaemia
      and lymphoma. However, clinical trials applying NK cells have not been as
      efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma
      (RAF) inhibitors exhibit increased tumour infiltration by immune cells,
      suggesting that a combination of RAF inhibitors with immunotherapy might be
      beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto
      oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed
      an in-vitro investigation on the potential of clinically relevant short-acting
      tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK
      cells from healthy human blood donors were thus treated with sorafenib, sunitinib
      or the pan-RAF inhibitor ZM336372 during ex-vivo expansion. Functional outcomes
      assessed after washout of the drugs included cytokine production, degranulation,
      cytotoxicity, apoptosis induction and signal transduction with/without target
      cell contact. Paradoxically, sorafenib enhanced NK cell effector functions in a
      time- and dose-dependent manner by raising the steady-state activation level. Of
      note, this did not lead to NK cell exhaustion, but enhanced activity against
      target cells such as K562 or Daudis mediated via the RAS/RAF/extracellular
      regulated kinase (ERK) pathway, but not via protein kinase B (AKT). Our data will
      pave the path to develop a rationale for the considered use of RAF inhibitors
      such as sorafenib for pre-activation in NK cell-based adoptive immune therapy.

PMID- 29573267
TI  - Dietary Fatty Acids Differentially Regulate Secretion of Adiponectin and
      Interleukin-6 in Primary Canine Adipose Tissue Culture.
AB  - The aim of this study was to determine the effect of n3 polyunsaturated fatty
      acids (PUFA) on canine adipose tissue secretion of adiponectin, interleukin-6
      (IL6), and tumor necrosis factor-alpha (TNFalpha). Subcutaneous and omental
      visceral adipose tissue samples were collected from 16 healthy intact female
      dogs. Concentrations of adiponectin were measured in mature adipocyte cultures,
      and concentrations of IL6 and TNFalpha were measured in undifferentiated
      stromovascular cell (SVC) cultures following treatment with eicosapentaenic acid
      (EPA, 20:5n-3), arachidonic acid (ARA, 20:4n-6), or palmitic acid (PAM, 16:0) at
      25, 50, or 100 MUM. Secretion of adiponectin from mature adipocytes was higher (p
      < 0.001) following EPA treatment at 50 MUM compared to control in subcutaneous
      tissue, and higher following EPA treatment compared to PAM treatment at 25 MUM in
      both subcutaneous (p < 0.001) and visceral tissues (p = 0.010). Secretion of IL6
      from SVC derived from subcutaneous tissue was lower following EPA treatment and
      higher following PAM treatment compared to control both at 50 MUM (p = 0.001 and
      p = 0.041, respectively) and 100 MUM (p = 0.013 and p < 0.001, respectively).
      These findings of stimulation of adiponectin secretion and inhibition of IL6
      secretion by EPA, and stimulation of IL6 secretion by PAM, are consistent with
      findings of increased circulating concentrations of adiponectin and decreased
      circulating concentration of IL6 in dogs supplemented with dietary fish oil, and
      show that the effect of fish oil on circulating concentrations of adiponectin and
      IL6 is, at least partially, the result of local effects of EPA and PAM on adipose
      tissue.

PMID- 29573268
TI  - Simulations of optically switchable molecular machines for particle transport.
AB  - A promising application for design and deployment of molecular machines is
      nanoscale transport, driven by artificial cilia. In this contribution, we present
      several further steps toward this goal, beyond our first-generation artificial
      cilium (Raeker et al., J. Phys. Chem. A 2012, 116, 11241). Promising new
      azobenzene-derivatives were tested for use as cilium motors. Using a QM/MM
      partitioning in on-the-fly photodynamics, excited-state surface-hopping
      trajectories were calculated for each isomerization direction and each motor
      version. The methods used were reparametrized semiempirical quantum chemistry
      together with floating-occupation configuration interaction as the QM part and
      the OPLSAA-L forcefield as MM part. In addition, we simulated actual particle
      transport by a single cilium attached to a model surface, with varying attachment
      strengths and modes, and with transport targets ranging from single atoms to
      multi-molecule arrangements. Our results provide valuable design guidelines for
      cilia-driven nanoscale transport and emphasize the need to carefully select the
      whole setup (not just the cilium itself, but also its surface attachment and the
      dynamic cilium-target interaction) to achieve true transport. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29573269
TI  - Improved laparoscopic skills in gynaecology trainees following a simulation
      training program using take-home box trainers.
AB  - BACKGROUND: Lack of time and access to equipment are recognised barriers to
      simulation training. AIM: To investigate the effect of a take-home laparoscopic
      simulator training program on the laparoscopic skills of gynaecology trainees.
      METHOD: Participants (n = 17 in 2015, n = 16 in 2016) were supplied with a box
      trainer, associated equipment and instructions on self-directed training. A
      program was designed and implemented in 2015 comprising of ten weekly
      laparoscopic skills tasks and modified in 2016 to eight monthly tasks. Half of
      the participants were randomly allocated a supervisor. Participants performed
      baseline and post-training assessments of laparoscopic skills in a box trainer
      task (thread transfer) and virtual reality simulator tasks (laparoscopic tubal
      ligation and bilateral oophorectomy). RESULTS: Trainees in 2015 demonstrated an
      improvement in the median time to complete the laparoscopic tubal ligation task
      (baseline 124 s vs post-training 91 s, P = 0.041). There was no difference in the
      number of tubal ligation bleeding incidents, or in the time taken to complete the
      box trainer thread transfer task. In 2016 trainees demonstrated improvement in
      tubal ligation time (baseline 251 vs 71 post-training, P = 0.021) and bilateral
      oophorectomy time (baseline 891 s vs 504 post-training, P = 0.025). There was no
      significant difference in other outcome measures. There was no difference found
      in performance when groups were compared by supervisor allocation. CONCLUSION: A
      take-home box trainer simulation-training program was associated with improvement
      in laparoscopic skills. This type of program may improve trainee access to
      simulation training.

PMID- 29573270
TI  - Identifying the germ cells during embryogenesis and gametogenesis by germ-line
      gene vasa in an anadromous fish, American shad Alosa sapidissima.
AB  - American shad Alosa sapidissima, an anadromous clupeid, exhibits variation in
      reproductive strategies, including semelparity and iteroparity. It provides an
      excellent model for studying the behaviour of germ cells in anadromous fish
      during their migration from sea to river. The vasa gene was characterized in A.
      sapidissima as a germ-cell marker to elaborate the process of germ-cell
      development and differentiation in anadromous species. A complementary (c)DNA
      fragment of 819 bp, partial open reading frame (ORF), was cloned by degenerate
      PCR and named as ASvas. In adult A. sapidissima, vasa transcript was exclusively
      detected in gonads by reverse-transcription (RT)-PCR. Through chromogenic in situ
      hybridization, the vasa messenger (m)RNA was specifically detected in primordial
      germ cells (PGC) in embryos and germ cells at early stages in ovary and testis.
      Besides, the cellular distribution profile of Vasa protein also proved that vasa
      gene could be used as a germ-line marker to trace the PGCs migration during
      embryogenesis and the germ-cell differentiation during gametogenesis in A.
      sapidissima. During embryogenesis, the migrating PGCs were clearly detected at
      tail-bud stage and the PGCs reached the genital ridge at the stage of pre
      hatching stage in A. sapidissima embryos. During gametogenesis, the Vasa protein
      was dynamically expressed in differentiating germ cells at different stages in
      adult gonads. As far as we know, this is the first report to demonstrate the PGCs
      migration and germ-cell differentiation through vasa gene expression in the
      anadromous species. The findings will pave a way for investigating germ-cell
      development and maturation in the A. sapidissima and other anadromous fish.

PMID- 29573271
TI  - A study of skin disease spectrum occurring in Angola phototype V-VI population in
      Luanda.
AB  - BACKGROUND: Prevalence of skin diseases in Luanda (Angola) is unknown, and
      publications are barely found in the literature. We aim to describe, for the
      first time, the frequency of skin disease spectrum in phototype V-VI Angolan
      population in Luanda City. METHODS: We included Fitzpatrick phototype V-VI
      Angolan patients who consulted the Dermatology Unit in Luanda Medical Center
      during a 1-year period. Medical information was recovered from the electronic
      database, and diagnoses were based on ICD-10. Only the main complaint was
      registered, and the results were classified according to age and sex. Criteria
      exclusion consisted of incomplete clinical records, Fitzpatrick phototype I-IV
      Angolan, or foreign patients from the study. RESULTS: From a total of 3938
      patients, 3554 met the inclusion criteria, of which 2742 were adults 13 years or
      older. In this group, acne (23.6%), dermatophytosis (11.0%), and pityriasis
      versicolor (8.6%) were the main complaints. On the other hand, in the pediatric
      population (n = 812), atopic dermatitis (29.4%), tinea capitis (13.7%), and
      molluscum contagiosum (12.5%) were the most frequent disorders. In adult females,
      acne (31.3%) was the main condition, while in adult males, dermatophytosis
      (13.5%). In children, the frequency of atopic dermatitis was comparable: 29.1%
      and 28.6% in girls and boys, respectively. CONCLUSIONS: We published for the
      first time the frequency of the skin disease spectrum in Fitzpatrick phototype V
      VI Angolan population in Luanda City, highlighting the prevalence of acne,
      dermatophytosis, and atopic dermatitis.

PMID- 29573272
TI  - A case of disseminated follicular spicules in HIV-associated follicular syndrome
      in the absence of the seven known human polyomaviruses, suggesting that this
      disorder is distinct from trichodysplasia spinulosa.

PMID- 29573273
TI  - Patterns of topical corticosteroids prescriptions in children with asthma.
AB  - OBJECTIVES: To study topical corticosteroid use in Dutch asthmatic children using
      pharmacy dispensing data and to assess whether Dutch physicians prescribe topical
      corticosteroids in this population according to clinical guidelines. METHODS:
      Medication histories of children using asthma medication were extracted from the
      pharmacy dispensing system in 100 Dutch community pharmacies. The incidence rate
      and the potency of topical corticosteroid prescriptions per age were assessed.
      The topical corticosteroid incidence rates of the different age groups were
      compared using the Pearson chi-square test. Generalized linear models were used
      to study the prescription behavior of general practitioners and atopic dermatitis
      related specialists regarding different classes of topical corticosteroids.
      RESULTS: Thirty percent of the infants received a topical corticosteroid
      prescription, compared with 15%-18% of the children aged 4 and older. Similarly,
      the mean number of topical corticosteroid prescriptions in infants was 2.2 per
      year, compared with 1.6-1.9 in children aged 4 and older. In concordance with the
      clinical guidelines, we observed that atopic dermatitis-related specialists more
      often prescribed first prescriptions of potent and very potent topical
      corticosteroids than general practitioners (relative risk = 2.55, 95% confidence
      interval = 1.79-3.63). Statistically significant differences (P < .01) were found
      between potencies of prescribed topical corticosteroids. CONCLUSION: Younger
      children receive more topical corticosteroid prescriptions than children aged 4
      and older, and there is a statistically significantly higher prescription rate of
      topical corticosteroid for infants. Sometimes general practitioners do not follow
      guidelines and prescribe more-potent topical corticosteroids without a prior
      prescription of the same potency by a specialist.

PMID- 29573275
TI  - A role for ALF4 during gall and giant cell development in the biotic interaction
      between Arabidopsis and Meloidogyne spp.
AB  - Root-knot nematodes (RKNs; Meloidogyne spp.) are a major pest for the agriculture
      worldwide. RKNs induce specialized feeding cells (giant cells, GCs) inside galls
      which are de novo formed pseudo-organs in the roots that share similarities with
      other developmental processes as lateral root (LR) and callus formation or
      grafting involving new vascular development or pericycle proliferation. Hence, it
      is pertinent to study the molecular mechanisms directing the plant-nematode
      interaction. In this respect, ALF4 is a key gene during LR formation, vascular
      vessels reconnection in grafting, hormone-induced callus formation or de novo
      root organogenesis from leaf explants. Our results show that ALF4 is also induced
      in galls at early infection stages in an auxin-independent way. Furthermore, ALF4
      activity is necessary for the formation of proper galls and GCs, as the mutant
      alf4-1 presents aberrant galls and GCs with severe structural abnormalities
      leading to a dramatic reduction in the nematode egg production. However, a low
      reproduction rate is maintained, that might be explained by the local auxin
      maximum build by the nematodes in galls, partially rescuing alf4-1 phenotype.
      This would be similar to the partial rescue described for LR formation with
      exogenous auxins and also agrees with the LR emergence from alf4-1 galls but not
      from uninfected roots. In addition, ALF4 is also induced in syncytia formed by
      cyst nematodes. All these data support a pivotal role for ALF4 during de novo
      organogenesis processes induced by endoparasitic nematodes, in addition to its
      role in LR formation, callus development or vessel reconnection during grafting.

PMID- 29573274
TI  - Listen to the public and fulfil their information interests - translating vaccine
      communication research findings into guidance for regulators.
AB  - Regulatory authorities have a crucial role in communicating about the vaccines
      they license. In terms of content and timing, their communication to the public
      is usually driven by data on quality, safety and efficacy. However, concerns over
      safety and vaccine hesitancy have emerged in some communities in various
      countries, and this demands a new approach to communication, starting with
      listening to the public debate. Reviewing communication research findings, coming
      in particular from the cognitive, decision-making and media sciences, constitutes
      one mechanism of listening and has led the European Union (EU) regulatory network
      to developing guidance about which common concerns and information needs of the
      public to address through proactive and prepared communication. The guidance has
      been welcomed by EU and international fora. The current article summarizes the
      recommendations and shares the underlying research findings, as well as a proof
      of concept that communication research can be valuable for regulators. It is
      critical that regulators integrate the communication process with product risk
      assessment in the framework of pharmacovigilance, to ensure that public concerns
      are addressed in the assessments and that information about evidence and
      uncertainty relating to safety is provided to the public and vaccination policy
      makers in a specific, clear and accurate manner. Additionally, information from
      regulatory authorities should support healthcare professionals in their
      communication with patients. Meeting the information interests of the public is
      the principal prerequisite for informed decisions as well as safe and effective
      use of vaccines and medicines overall. This is also fundamental for trust in the
      authorities' commitment to patient and population health.

PMID- 29573277
TI  - The effects of the Union for International Cancer Control/American Joint
      Committee on Cancer Tumour, Node, Metastasis system version 8 on staging of
      differentiated thyroid cancer: a comparison to version 7.
AB  - OBJECTIVE: To assess the changes resulting from the changes from UICC/AJCC TNM
      version 7 to version 8 and to subsequently determine whether TNM version 8 is an
      improvement compared to previous iterations of the TNM system and other staging
      systems for differentiated thyroid cancer (DTC) with regard to prognostic power.
      DESIGN: Database study of DTC patients treated in our centre between 1978 up to
      and including 1 July 2014. Results were compared to our previous comparison of
      prognostic systems using the same data set. PATIENTS: 2257 DTC patients.
      MEASUREMENTS: Staging in accordance with TNM 7 and TNM 8. Thyroid cancer-specific
      mortality; comparison was based on p-values of univariate Cox regression analyses
      as well as analysis of the proportion of variance explained (PVE). RESULTS: There
      is a redistribution from stage 3 to lower stages affecting 206 (9.1%) patients.
      DTC-related mortality according to Kaplan-Meier for younger and older patients in
      TNM 7 had a slightly lower prognostic power than that in accordance with TNM 8 (P
      = 8.0 10-16 and P = 1.5 10-21 , respectively). Overall staging is lower in
      627/2257 (27.8%) patients. PVE (TNM 7: 0.29; TNM 8: 0.28) and the P-value of Cox
      regressions (TNM 7: P = 7.1*10-52 ; TNM 8: P = 3.9*10-49 ) for TNM version 8 are
      marginally lower than that for TNM version 7, but still better than for any other
      DTC staging system. CONCLUSION: TNM 8 results in a marked downstaging of patients
      compared to TNM 7. Although some changes, like the change in age boundary, appear
      to be associated with an improvement in prognostic power, the overall effect of
      the changes does not improve the predictive power compared to TNM 7.

PMID- 29573276
TI  - Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics.
AB  - KEY POINTS: Ion current kinetics are commonly represented by current-voltage
      relationships, time constant-voltage relationships and subsequently mathematical
      models fitted to these. These experiments take substantial time, which means they
      are rarely performed in the same cell. Rather than traditional square-wave
      voltage clamps, we fitted a model to the current evoked by a novel sum-of
      sinusoids voltage clamp that was only 8 s long. Short protocols that can be
      performed multiple times within a single cell will offer many new opportunities
      to measure how ion current kinetics are affected by changing conditions. The new
      model predicts the current under traditional square-wave protocols well, with
      better predictions of underlying currents than literature models. The current
      under a novel physiologically relevant series of action potential clamps is
      predicted extremely well. The short sinusoidal protocols allow a model to be
      fully fitted to individual cells, allowing us to examine cell-cell variability in
      current kinetics for the first time. ABSTRACT: Understanding the roles of ion
      currents is crucial to predict the action of pharmaceuticals and mutations in
      different scenarios, and thereby to guide clinical interventions in the heart,
      brain and other electrophysiological systems. Our ability to predict how ion
      currents contribute to cellular electrophysiology is in turn critically dependent
      on our characterisation of ion channel kinetics - the voltage-dependent rates of
      transition between open, closed and inactivated channel states. We present a new
      method for rapidly exploring and characterising ion channel kinetics, applying it
      to the hERG potassium channel as an example, with the aim of generating a
      quantitatively predictive representation of the ion current. We fitted a
      mathematical model to currents evoked by a novel 8 second sinusoidal voltage
      clamp in CHO cells overexpressing hERG1a. The model was then used to predict over
      5 minutes of recordings in the same cell in response to further protocols: a
      series of traditional square step voltage clamps, and also a novel voltage clamp
      comprising a collection of physiologically relevant action potentials. We
      demonstrate that we can make predictive cell-specific models that outperform the
      use of averaged data from a number of different cells, and thereby examine which
      changes in gating are responsible for cell-cell variability in current kinetics.
      Our technique allows rapid collection of consistent and high quality data, from
      single cells, and produces more predictive mathematical ion channel models than
      traditional approaches.

PMID- 29573278
TI  - The origin and evolution of mycorrhizal symbioses: from palaeomycology to
      phylogenomics.
AB  - Contents Summary 1012 I. Introduction 1013 II. The mycorrhizal symbiosis at the
      dawn and rise of the land flora 1014 III. From early land plants to early trees:
      the origin of roots and true mycorrhizas 1016 IV. The diversification of the AM
      symbiosis 1019 V. The ECM symbiosis 1021 VI. The recently evolved ericoid and
      orchid mycorrhizas 1023 VII. Limits of paleontological vs genetic approaches and
      perspectives 1023 Acknowledgements 1025 References 1025 SUMMARY: The ability of
      fungi to form mycorrhizas with plants is one of the most remarkable and enduring
      adaptations to life on land. The occurrence of mycorrhizas is now well
      established in c. 85% of extant plants, yet the geological record of these
      associations is sparse. Fossils preserved under exceptional conditions provide
      tantalizing glimpses into the evolutionary history of mycorrhizas, showing the
      extent of their occurrence and aspects of their evolution in extinct plants. The
      fossil record has important roles to play in establishing a chronology of when
      key fungal associations evolved and in understanding their importance in
      ecosystems through time. Together with calibrated phylogenetic trees, these
      approaches extend our understanding of when and how groups evolved in the context
      of major environmental change on a global scale. Phylogenomics furthers this
      understanding into the evolution of different types of mycorrhizal associations,
      and genomic studies of both plants and fungi are shedding light on how the
      complex set of symbiotic traits evolved. Here we present a review of the main
      phases of the evolution of mycorrhizal interactions from palaeontological,
      phylogenetic and genomic perspectives, with the aim of highlighting the potential
      of fossil material and a geological perspective in a cross-disciplinary approach.

PMID- 29573279
TI  - FDG-PET metabolic tumor parameters for the reirradiation of recurrent head and
      neck cancer.
AB  - OBJECTIVE: The utility of fluorodeoxyglucose positron emission tomography (FDG
      PET) imaging to predict outcome has been well-established for patients undergoing
      definitive radiation in the initial management of head and neck cancer. However,
      the usefulness of this modality in the recurrent setting remains uncertain. We
      sought to evaluate the prognostic value of metabolic tumor parameters measured on
      FDG-PET in patients treated by reirradiation for recurrent head and neck cancer.
      METHODS: Thirty-four tumors occurring in 29 patients were reirradiated and were
      evaluable. The most common disease sites were the oropharynx (n = 9), oral cavity
      (N = 8), and nasopharynx (n = 6). Potential correlations of FDG-PET maximum
      standardized uptake value (SUV) and metabolic tumor volume (MTV) with survival
      endpoints were explored. Multivariate analysis was performed using Cox
      proportional hazard. RESULTS: The median MTV, SUV, and gross tumor volume, as
      delineated using the 50% SUVmax threshold, were 366 cc (range, 0-3,567 cc), 8.1
      (range, 0-25), and 48.5 cc (range, 1-190 cc), respectively. On univariate
      analysis, both MTVs (as measured as a continuous variable and using the median
      value of 266 cc as cutoff) were predictive of decreased overall survival (P <
      0.05 for both). A strong trend toward decreased progression-free survival (P =
      0.05), in-field control (P = 0.06), and locoregional control (P = 0.07) was also
      observed with increasing MTV when analyzed as a continuous variable. Multi
      variate analysis confirmed MTV as an independent predictor of mortality.
      CONCLUSION: The PET-derived parameter MTV may serve as a potentially valuable
      factor for risk stratification and for guiding treatment in future reirradiation
      trials. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2345-2350, 2018.

PMID- 29573280
TI  - Invisible cobwebs in teamwork-Impediments to the care of patients with heart
      failure: A qualitative study.
AB  - AIM: This study was done to explore team member's perception regarding
      impediments to the care of patients with heart failure (HF). BACKGROUND: Complex,
      chronic HF patients require interprofessional teams to address their multiple
      health needs. Working in a team has some challenges in achieving goals.
      Sociocultural differences in Iranian therapeutic team members causes some
      impediments to provide effective care in the form of a team. METHODS: Data were
      collected through unstructured in-depth interviews with 58 team members in caring
      for the patients with HF. The interviews were transcribed verbatim and analyzed
      using content analysis. RESULTS: Twelve subcategories and 5 categories were
      formed: inefficient supportive network, inadequacy of training and treatment,
      affectability and variability challenges for the team, arduous working
      conditions, and heavy physicians shadow on nursing. The final theme emerged as
      "Invisible cobwebs in teamwork." CONCLUSION: Despite teamwork being an efficient
      way of achieving goals, several impediments like a cobweb hinder it from becoming
      fully exploited. Teamwork has a desirable output when all the members feel the
      same sense of authority and see themselves in an integrated team and managers
      have a crucial role in removing these impediments.

PMID- 29573282
TI  - Tackling parents' misperceptions about their children's weight issues needs
      careful handling.

PMID- 29573281
TI  - Surviving neoliberalism, maintaining values: Community health mergers in
      Victoria, Australia.
AB  - PURPOSE: Independent, not-for-profit community health services in the state of
      Victoria, Australia, provide one of that country's few models of comprehensive
      primary health care (PHC). Recent amalgamations among some such agencies created
      regional-sized community health organisations, in a departure from this sector's
      traditionally small local structure. This study explored the motivations, desired
      outcomes, and decision-making process behind these mergers. METHODOLOGY:
      Qualitative exploratory study was based on 26 semistructured interviews with key
      informants associated with 2 community health mergers, which took place in 2014
      in Victoria, Australia. Thematic data analysis was influenced by concepts derived
      from institutional theory. FINDINGS: Becoming bigger by merging was viewed as the
      best way to respond to mounting external pressures, such as increasingly
      neoliberal funding mechanisms, perceived as threatening survival. Desired
      outcomes were driven by comprehensive PHC values, and related to creating
      organisational capacity to continue providing quality services to disadvantaged
      communities. ORIGINALITY/VALUE: This study offers insights into decision-making
      processes geared towards protecting the comprehensiveness of PHC service delivery
      for disadvantaged communities, ensuring financial viability, and surviving
      neoliberal economic policy whilst preserving communitarian values. These are
      relevant to an international audience, within a global context of rising health
      inequities, increasingly tight fiscal environments, and growing neoliberal
      influences on health policymaking and funding.

PMID- 29573283
TI  - Thermal Conductivity of Polymers and Their Nanocomposites.
AB  - Polymers are usually considered as thermal insulators, and their applications are
      limited by their low thermal conductivity. However, recent studies have shown
      that certain polymers have surprisingly high thermal conductivity, some of which
      are comparable to that in poor metals or even silicon. Here, the experimental
      achievements and theoretical progress of thermal transport in polymers and their
      nanocomposites are outlined. The open questions and challenges of existing
      theories are discussed. Special attention is given to the mechanism of thermal
      transport, the enhancement of thermal conductivity in polymer
      nanocomposites/fibers, and their potential application as thermal interface
      materials.

PMID- 29573285
TI  - The very question of future development of extremely preterm infants.

PMID- 29573284
TI  - Materials for Neural Differentiation, Trans-Differentiation, and Modeling of
      Neurological Disease.
AB  - Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic
      cells trans-differentiation is a promising approach for cell replacement in
      neurodegenerative diseases and provides a powerful tool for investigating neural
      development, modeling neurological diseases, and uncovering the mechanisms that
      underlie diseases. Advancing the materials that are applied in neural
      differentiation and trans-differentiation promotes the safety, efficiency, and
      efficacy of neuron regeneration. In the neural differentiation process, matrix
      materials, either natural or synthetic, not only provide a structural and
      biochemical support for the monolayer or three-dimensional (3D) cultured cells
      but also assist in cell adhesion and cell-to-cell communication. They play
      important roles in directing the differentiation of PSCs into neural cells and
      modeling neurological diseases. For the trans-differentiation of neural cells,
      several materials have been used to make the conversion feasible for future
      therapy. Here, the most current applications of materials for neural
      differentiation for PSCs, neuronal trans-differentiation, and neurological
      disease modeling is summarized and discussed.

PMID- 29573286
TI  - Self-Reporting Fiber-Reinforced Composites That Mimic the Ability of Biological
      Materials to Sense and Report Damage.
AB  - Sensing of damage, deformation, and mechanical forces is of vital importance in
      many applications of fiber-reinforced polymer composites, as it allows the
      structural health and integrity of composite components to be monitored and
      microdamage to be detected before it leads to catastrophic material failure.
      Bioinspired and biomimetic approaches to self-sensing and self-reporting
      materials are reviewed. Examples include bruising coatings and bleeding
      composites based on dye-filled microcapsules, hollow fibers, and vascular
      networks. Force-induced changes in color, fluorescence, or luminescence are
      achieved by mechanochromic epoxy resins, or by mechanophores and force-responsive
      proteins located at the interface of glass/carbon fibers and polymers. Composites
      can also feel strain, stress, and damage through embedded optical and electrical
      sensors, such as fiber Bragg grating sensors, or by resistance measurements of
      dispersed carbon fibers and carbon nanotubes. Bioinspired composites with the
      ability to show autonomously if and where they have been damaged lead to a
      multitude of opportunities for aerospace, automotive, civil engineering, and wind
      turbine applications. They range from safety features for the detection of barely
      visible impact damage, to the real-time monitoring of deformation of load-bearing
      components.

PMID- 29573287
TI  - Self-Powered Wearable Electronics Based on Moisture Enabled Electricity
      Generation.
AB  - Most state-of-the-art electronic wearable sensors are powered by batteries that
      require regular charging and eventual replacement, which would cause
      environmental issues and complex management problems. Here, a device concept is
      reported that can break this paradigm in ambient moisture monitoring-a new class
      of simple sensors themselves can generate moisture-dependent voltage that can be
      used to determine the ambient humidity level directly. It is demonstrated that a
      moisture-driven electrical generator, based on the diffusive flow of water in
      titanium dioxide (TiO2 ) nanowire networks, can yield an output power density of
      up to 4 uW cm-2 when exposed to a highly moist environment. This performance is
      two orders of magnitude better than that reported for carbon-black generators.
      The output voltage is strongly dependent on humidity of ambient environment. As a
      big breakthrough, this new type of device is successfully used as self-powered
      wearable human-breathing monitors and touch pads, which is not achievable by any
      existing moisture-induced-electricity technology. The availability of high-output
      self-powered electrical generators will facilitate the design and application of
      a wide range of new innovative flexible electronic devices.

PMID- 29573288
TI  - Synaptotagmin-11 Is a novel hotspot in the pathogenesis of parkin-linked
      Parkinson's disease: New implications for clinical targeting.

PMID- 29573289
TI  - Electrocatalytic Hydroxylation of Sterols by Steroid C25 Dehydrogenase from
      Sterolibacterium denitrificans.
AB  - The electrochemically driven catalysis of the complex molybdoenzyme steroid C25
      dehydrogenase (S25DH) from the beta-Proteobacterium Sterolibacterium
      denitrificans is reported. S25DH catalyses the oxygen-independent regioselective
      hydroxylation of the tertiary C25 atom of sterols and also their derivatives.
      Cholest-4-en-3-one is a native substrate for S25DH, which produces 25
      hydroxycholest-4-en-3-one as a product of catalytic turnover. Cholecalciferol
      (vitD3 ) is also a substrate. S25DH was immobilised on a modified gold working
      electrode with the co-adsorbent chitosan. The complexes ferricyanide ([Fe(CN)6 ]3
      ) and ferrocenium methanol (FM+ ) are effective artificial electron acceptors
      from S25DH and act as mediators of electron transfer between the electrode and
      the enzyme. 2-Hydroxypropyl-beta-cyclodextrin (HPCD) was employed as a sterol
      solubiliser, in addition to 2-methoxyethanol. The catalytic activity varied,
      depending upon the concentration of solubiliser in the reaction mixture. Parallel
      studies with [Fe(CN)6 ]3- as a chemical (as opposed to electrochemical) oxidant
      coupled to HPLC analysis show that S25DH is capable of oxidising both vitD3 and
      its less stable isomer, pre-vitD3 , and that the former substrate is stabilised
      by HPCD.

PMID- 29573290
TI  - Intercalated Water and Organic Molecules for Electrode Materials of Rechargeable
      Batteries.
AB  - The intrinsic limitations of lithium-ion batteries (LIBs) with regard to safety,
      cost, and the availability of raw materials have promoted research on so-called
      "post-LIBs". The recent intense research of post-LIBs provides an invaluable
      lesson that existing electrode materials used in LIBs may not perform as well in
      post-LIBs, calling for new material designs compliant with emerging batteries
      based on new chemistries. One promising approach in this direction is the
      development of materials with intercalated water or organic molecules, as these
      materials demonstrate superior electrochemical performance in emerging battery
      systems. The enlarged ionic channel dimensions and effective shielding of the
      electrostatic interaction between carrier ions and the lattice host are the
      origins of the observed electrochemical performance. Moreover, these intercalants
      serve as interlayer pillars to sustain the framework for prolonged cycles.
      Representative examples of such intercalated materials applied to batteries based
      on Li+ , Na+ , Mg2+ , and Zn2+ ions and supercapacitors are considered, along
      with their impact in materials research.

PMID- 29573291
TI  - Digital analysis yields more reliable and accurate measures of dermal and
      epidermal thickness in histologically processed specimens compared to traditional
      methods.
AB  - Changes in the thickness of the dermis and epidermis have been described in the
      scenario of tissue expansion as well as inflammatory skin processes (psoriasis,
      contact hypersensitivity and so on). These changes have previously been
      quantified using ocular micrometers to obtain and then average a limited number
      of spot measurements, leading to suboptimal accuracy. We describe a rapid method
      of using freely available ImageJ software to analyze digitized images of fixed
      skin specimens. By determining the cross-sectional area and surface length of a
      skin layer, a simple calculation produces more accurate and reproducible
      measurements of its thickness compared to historical methods, with excellent
      inter-rater reliability.

PMID- 29573292
TI  - In vivo reflectance confocal microscopy combined with the 'spaghetti technique'
      for the identification of surgical margins of lentigo maligna: experience in 70
      patients.

PMID- 29573293
TI  - Reconfigurable Printed Liquids.
AB  - Liquids lack the spatial order required for advanced functionality. Interfacial
      assemblies of colloids, however, can be used to shape liquids into complex, 3D
      objects, simultaneously forming 2D layers with novel magnetic, plasmonic, or
      structural properties. Fully exploiting all-liquid systems that are structured by
      their interfaces would create a new class of biomimetic, reconfigurable, and
      responsive materials. Here, printed constructs of water in oil are presented.
      Both form and function are given to the system by the assembly and jamming of
      nanoparticle surfactants, formed from the interfacial interaction of
      nanoparticles and amphiphilic polymers that bear complementary functional groups.
      These yield dissipative constructs that exhibit a compartmentalized response to
      chemical cues. Potential applications include biphasic reaction vessels, liquid
      electronics, novel media for the encapsulation of cells and active matter, and
      dynamic constructs that both alter, and are altered by, their external
      environment.

PMID- 29573294
TI  - Anti-inflammatory therapy with tumour necrosis factor inhibitors is associated
      with reduced risk of major adverse cardiovascular events in psoriasis.
AB  - BACKGROUND: Psoriasis is a systemic chronic inflammatory condition associated
      with increased risk of cardiovascular disease. Data demonstrating that decreased
      skin inflammation reduces cardiovascular events in patients with psoriasis may be
      generalizable to other chronic inflammatory states with heightened cardiovascular
      risk. OBJECTIVE: To determine whether tumour necrosis factor inhibitor (TNFi)
      therapy is associated with decreased major adverse cardiovascular events (MACE)
      in patients with psoriasis. METHODS: In this retrospective cohort study using the
      KPSC health plan, patients had at least three ICD-9 codes for psoriasis and no
      antecedent MACE codes. Propensity score-adjusted multivariable Cox regression
      assessed hazard ratios (HR) of MACE associated with TNFi use. RESULTS: After
      adjusting for cardiovascular risk factors, the TNFi cohort had significantly
      lower MACE HR compared with the topical cohort (HR, 0.80; 95% CI, 0.66-0.98). The
      oral/phototherapy cohort had similar MACE HR compared with the topical cohort
      (HR, 1.19 (95% CI, 0.99-1.42)). CONCLUSIONS: We observed significantly lower MACE
      risk in patients with psoriasis receiving TNFi compared to topical or
      oral/phototherapy agents. TNFi therapy may have benefits beyond skin disease in
      mitigating cardiovascular event risk.

PMID- 29573295
TI  - Enrichment of Precious Metals from Wastewater with Core-Shell Nanoparticles of
      Iron.
AB  - Large-scale deployment of zero-valent iron nanoparticles for enrichment and
      recovery of gold from industrial wastewater is reported. Iron nanoparticles have
      a core-shell structure in which a metallic iron core is enclosed with a thin
      layer of iron oxides/hydroxides. The two nanocomponents offer synergistic
      functions for rapid separation, enrichment, and stabilization of metal ions such
      as Au, Ag, Ni, and Cu. Thanks to the advantages of small size, large surface
      area, and high reactivity, only a small amount of iron nanoparticles are needed.
      The recovered nanoparticles thus contain precious metals well above conventional
      metal ores (e.g., >100 g Au ton-1 ). Cost-effective recovery of precious metals
      from trace-level sources such as wastewater looks promising.

PMID- 29573296
TI  - Large-Scale Synthesis and Medical Applications of Uniform-Sized Metal Oxide
      Nanoparticles.
AB  - Thanks to recent advances in the synthesis of high-quality inorganic
      nanoparticles, more and more types of nanoparticles are becoming available for
      medical applications. Especially, metal oxide nanoparticles have drawn much
      attention due to their unique physicochemical properties and relatively
      inexpensive production costs. To further promote the development and clinical
      translation of these nanoparticle-based agents, however, it is highly desirable
      to reduce unwanted interbatch variations of the nanoparticles because
      characterizing and refining each batch are costly, take a lot of effort, and,
      thus, are not productive. Large-scale synthesis is a straightforward and economic
      pathway to minimize this issue. Here, the recent achievements in the large-scale
      synthesis of uniform-sized metal oxide nanoparticles and their biomedical
      applications are summarized, with a focus on nanoparticles of transition metal
      oxides and lanthanide oxides, and clarifying the underlying mechanism for the
      synthesis of uniform-sized nanoparticles. Surface modification steps to endow
      hydrophobic nanoparticles with water dispersibility and biocompatibility are also
      briefly described. Finally, various medical applications of metal oxide
      nanoparticles, such as bioimaging, drug delivery, and therapy, are presented.

PMID- 29573297
TI  - A simple and fast quantitative analysis of quinolizidine alkaloids and their
      biosynthetic precursor, lysine, in Sophora alopecuroides by hydrophilic
      interaction chromatography coupled with triple-quadrupole tandem mass
      spectroscopy.
AB  - INTRODUCTION: Different parts of Sophora alopecuroides L. (Fabaceae) have
      historically been used in traditional Chinese medicine for the treatment of
      dysentery and enteritis. This plant is also utilised as an important resource for
      industrial preparation of quinolizidine alkaloidal pharmaceuticals. OBJECTIVE:
      Establish a reliable, simple and fast analytical method for the quantitative
      determination of the quinolizidine-type alkaloids and extend understanding of the
      metabolism of quinolizidine-type alkaloids in S. alopecuroides. METHODS:
      Hydrophilic interaction chromatography coupled with triple-quadrupole tandem mass
      spectrometry (HILIC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode were
      used to determine seven quinolizidine-type alkaloids and their biosynthetic
      precursor, lysine, in S. alopecuroides. RESULTS: A good separation was obtained
      on an ultra high-performance liquid chromatography (UHPLC) amide column within 7
      min. The overall limits of detection (LODs) were between 1.13 and 2.81 ng/ml, and
      limits of quantitation (LOQs) were between 3.80 and 8.48 ng/ml. The developed
      method was successfully applied to 21 samples of S. alopecuroides. The seeds had
      the highest concentration of alkaloids among the different plant parts.
      Oxymatrine and oxysophocarpine were the two most abundant alkaloids in all of the
      different parts and at different phenological growth stages. The contents of
      quinolizidine alkaloids showed correlations with lysine. CONCLUSION: A rapid and
      sensitive analytical method was established for the simultaneous determination of
      seven quinolizidine-type alkaloids and their biosynthetic precursor, lysine, in
      S. alopecuroides; the content of lysine may be used as a marker to predict
      alkaloid production.

PMID- 29573298
TI  - Anti-ageing effect of red ginseng revealed by urinary metabonomics using RRLC-Q
      TOF-MS.
AB  - INTRODUCTION: Red ginseng (RG) is one of the main processed products of the roots
      and rhizomes of Panax ginseng C.A. Meyer and is used for anti-ageing. But how
      metabonomic influences of RG on the progress of ageing are less researched.
      OBJECTIVE: A metabonomic method was developed to study the characters of the
      ageing process and the effects of total ginsenosides of red ginseng (TGRG) on the
      progress of ageing. METHODS: Urine samples from four different ages (4, 12, 18
      and 24 months old) of rats and interference after TGRG were analysed by rapid
      resolution liquid chromatography coupled with quadruple-time-of-flight mass
      spectrometry (RRLC-Q-TOF-MS) and multivariate statistical analysis were performed
      for the pattern recognition and characteristic metabolites identification.
      RESULTS: Fourteen potential biomarkers were found and identified by MS/MS
      analysis by referring to authentic chemicals. The analysis of metabolic pathways
      indicated that the reduced energy and lipid metabolism, the decline of kidney
      function and amino acids metabolism disorders were the main features of ageing.
      After TGRG administration, lipid and amino acids metabolism of 18 and 24 month
      old rats were adjusted to restore a younger level, and nine related biomarkers in
      the ageing process reset to a younger level were recognised. CONCLUSION: These
      changes showed that TGRG may produce an anti-ageing effect by intervening in the
      lipid metabolism and correcting the amino acid metabolism disorders in ageing
      rats.

PMID- 29573300
TI  - Synthesis and Structure of a Stable Bis(methylene)-lambda4 -sulfane.
AB  - Bis(methylene)-lambda4 -sulfane 1, a >C=S=C< heterocumulene, was obtained as a
      red crystalline solid from the reaction between elemental sulfur and a carbenoid
      that contains sterically demanding silylalkyl groups. Under atmospheric
      conditions, and even at elevated temperatures, 1 exhibits extraordinary
      stability. The molecular structure and electron-density distribution of 1 were
      analyzed by single-crystal X-ray diffraction analysis, which revealed a bent
      C=S=C geometry with C=S=C pi-bonds. These results, combined with those of
      variable-temperature NMR measurements and theoretical calculations suggest a slow
      rotation of the S=C moieties in 1, the stability and structure of which were
      further examined by theoretical calculations.

PMID- 29573299
TI  - Revealing the Contribution of Individual Factors to Hydrogen Evolution Reaction
      Catalytic Activity.
AB  - For the electrochemical hydrogen evolution reaction (HER), the electrical
      properties of catalysts can play an important role in influencing the overall
      catalytic activity. This is particularly important for semiconducting HER
      catalysts such as MoS2 , which has been extensively studied over the last decade.
      Herein, on-chip microreactors on two model catalysts, semiconducting MoS2 and
      semimetallic WTe2 , are employed to extract the effects of individual factors and
      study their relations with the HER catalytic activity. It is shown that electron
      injection at the catalyst/current collector interface and intralayer and
      interlayer charge transport within the catalyst can be more important than
      thermodynamic energy considerations. For WTe2 , the site-dependent activities and
      the relations of the pure thermodynamics to the overall activity are measured and
      established, as the microreactors allow precise measurements of the type and area
      of the catalytic sites. The approach presents opportunities to study
      electrochemical reactions systematically to help establish rational design
      principles for future electrocatalysts.

PMID- 29573301
TI  - Early death and causes of death of people with Down syndrome: A systematic
      review.
AB  - BACKGROUND: It is thought that people with Down syndrome die younger than the
      general population, but that survival rates are improving. METHODS: Five
      databases were searched for keywords related to intellectual disabilities, Down
      syndrome and mortality. Strict inclusion criteria were applied. Information from
      34 selected studies was tabulated, extracted and synthesized. RESULTS: People
      with Down syndrome died about 28 years younger than the general population.
      Congenital heart anomalies, comorbidities, low birthweight, and Black and
      minority ethnicity influenced earlier age of death, as did younger maternal age
      and poorer parental education. Congenital heart anomalies and respiratory
      conditions were the leading causes of death, and more common than in the general
      population. Survival rates have improved over time, particularly for those with
      congenital heart anomalies. CONCLUSIONS: People with Down syndrome are living
      longer but still die younger of different causes than the general population.
      More robust comparative data are needed, and ethnic differences require further
      study.

PMID- 29573302
TI  - Human herpesvirus portal proteins: Structure, function, and antiviral prospects.
AB  - Herpesviruses (Herpesvirales) and tailed bacteriophages (Caudovirales) package
      their dsDNA genomes through an evolutionarily conserved mechanism. Much is known
      about the biochemistry and structural biology of phage portal proteins and the
      DNA encapsidation (viral genome cleavage and packaging) process. Although not at
      the same level of detail, studies on HSV-1, CMV, VZV, and HHV-8 have revealed
      important information on the function and structure of herpesvirus portal
      proteins. During dsDNA phage and herpesviral genome replication, concatamers of
      viral dsDNA are cleaved into single length units by a virus-encoded terminase and
      packaged into preformed procapsids through a channel located at a single capsid
      vertex (portal). Oligomeric portals are formed by the interaction of identical
      portal protein monomers. Comparing portal protein primary aa sequences between
      phage and herpesviruses reveals little to no sequence similarity. In contrast,
      the secondary and tertiary structures of known portals are remarkable. In all
      cases, function is highly conserved in that portals are essential for DNA
      packaging and also play a role in releasing viral genomic DNA during infection.
      Preclinical studies have described small molecules that target the HSV-1 and VZV
      portals and prevent viral replication by inhibiting encapsidation. This review
      summarizes what is known concerning the structure and function of herpesvirus
      portal proteins primarily based on their conserved bacteriophage counterparts and
      the potential to develop novel portal-specific DNA encapsidation inhibitors.

PMID- 29573303
TI  - Simplifying Imaging of the Abdominal Fetal Precordial Venous System.
AB  - The fetal precordial veins comprise a complex system of vessels delivering
      oxygenated blood from the placenta through the umbilical vein to the developing
      fetus. This system draws most of its nomenclature from the adult venous system.
      However, the direction of flow, as well as the relative size and prominence of
      the component vessels, differ from those in the postnatal circulation.
      Understanding the unique characteristics of the fetal circulation and its
      differences from the postnatal system can aid the sonographer in identifying
      normal1 and anomalous2 anatomy (Figure 1).

PMID- 29573304
TI  - The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.
AB  - OBJECTIVES: Discrimination between HIV-1 and HIV-2 is important to ensure
      appropriate antiretroviral treatment (ART) and epidemiological surveillance.
      However, serological tests have shown frequent mistyping when applied in the
      field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and
      ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS: Samples
      from 239 ART-naive HIV-infected patients from the Bissau HIV Cohort in Guinea
      Bissau were selected retrospectively based on the initial HIV typing performed in
      Bissau, ensuring a broad representation of HIV types. INNO-LIA results were
      interpreted by the newest software algorithm, and three independent observers
      read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for
      confirmation. RESULTS: INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV
      2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA
      and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive
      samples could be confirmed by the nucleic acid results. Overall, the observers
      found that the ImmunoComb results differed from the INNO-LIA results, with
      agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2.
      The combined kappa-score for agreement between the three observers was 0.955 (z
      score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three
      observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None
      of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS: There was
      accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb
      overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing
      is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.

PMID- 29573305
TI  - Accounting for disturbance history in models: using remote sensing to constrain
      carbon and nitrogen pool spin-up.
AB  - Disturbances such as wildfire, insect outbreaks, and forest clearing, play an
      important role in regulating carbon, nitrogen, and hydrologic fluxes in
      terrestrial watersheds. Evaluating how watersheds respond to disturbance requires
      understanding mechanisms that interact over multiple spatial and temporal scales.
      Simulation modeling is a powerful tool for bridging these scales; however, model
      projections are limited by uncertainties in the initial state of plant carbon and
      nitrogen stores. Watershed models typically use one of two methods to initialize
      these stores: spin-up to steady state or remote sensing with allometric
      relationships. Spin-up involves running a model until vegetation reaches
      equilibrium based on climate. This approach assumes that vegetation across the
      watershed has reached maturity and is of uniform age, which fails to account for
      landscape heterogeneity and non-steady-state conditions. By contrast, remote
      sensing, can provide data for initializing such conditions. However, methods for
      assimilating remote sensing into model simulations can also be problematic. They
      often rely on empirical allometric relationships between a single vegetation
      variable and modeled carbon and nitrogen stores. Because allometric relationships
      are species- and region-specific, they do not account for the effects of local
      resource limitation, which can influence carbon allocation (to leaves, stems,
      roots, etc.). To address this problem, we developed a new initialization approach
      using the catchment-scale ecohydrologic model RHESSys. The new approach merges
      the mechanistic stability of spin-up with the spatial fidelity of remote sensing.
      It uses remote sensing to define spatially explicit targets for one or several
      vegetation state variables, such as leaf area index, across a watershed. The
      model then simulates the growth of carbon and nitrogen stores until the defined
      targets are met for all locations. We evaluated this approach in a mixed pine
      dominated watershed in central Idaho, and a chaparral-dominated watershed in
      southern California. In the pine-dominated watershed, model estimates of carbon,
      nitrogen, and water fluxes varied among methods, while the target-driven method
      increased correspondence between observed and modeled streamflow. In the
      chaparral watershed, where vegetation was more homogeneously aged, there were no
      major differences among methods. Thus, in heterogeneous, disturbance-prone
      watersheds, the target-driven approach shows potential for improving
      biogeochemical projections.

PMID- 29573306
TI  - Involvement of microRNA miR-2b-3p in regulation of metabolic resistance to
      insecticides in Plutella xylostella.
AB  - The diamondback moth, Plutella xylostella, has developed extremely high levels of
      resistance to chlorantraniliprole and other classes of insecticides in the field.
      As microRNAs (miRNAs) play important roles in various biological processes
      through gene regulation, we examined the miRNA profile of P. xylostella in
      response to chlorantraniliprole exposure. RNA sequencing analysis showed that
      insecticide treatment caused significant changes in the abundance of some miRNAs.
      Increasing exposure time and insecticide concentration induced more dysregulated
      miRNAs in P. xylostella larvae. We also screened potential target genes for some
      of the differentially expressed miRNAs (such as miR-2b-3p, miR-14b-5p and let-7
      5p), which may play important roles in insecticide resistance development.
      Exposure of P. xylostella larvae to chlorantraniliprole caused considerable
      overexpression in the transcript levels of potential target genes cytochrome P450
      9f2 (CYP9F2) and 307a1 (CYP307a1). Application of miR-2b-3p and miR-14b-5p mimics
      significantly suppressed the relative transcript levels of CYP9F2 and CYP307a1,
      respectively, in a P. xylostella cell line. Furthermore, enrichment of P.
      xylostella diet with miR-2b-3p mimics significantly increased mortality in
      deltamethrin-resistant larvae when exposed to deltamethrin. The results suggest
      that miR-2b-3p may suppress CYP9F2 transcript levels in P. xylostella and
      consequently inhibit larval detoxification pathways. The findings provide an
      insight into possible role of miRNAs in regulation of metabolic resistance of
      insects to insecticides.

PMID- 29573307
TI  - Development of a cognitive behavioural therapy-based guided self-help
      intervention for adults with intellectual disability.
AB  - BACKGROUND: Despite strong evidence for cognitive behaviour therapy (CBT) in
      treating mental health, its use, thus far, has been limited for people with
      intellectual disabilities. This study describes a CBT-based guided self-help (CBT
      GSH) manual for individuals with intellectual disability, and focus groups
      explore the views of clinicians, therapists, support staff and managers. MATERIAL
      AND METHODS: Using a qualitative methodology, an expert team adapted the manual.
      Focus groups provided feedback, followed by thematic content analysis for
      modifications. RESULTS: Participants supported using the manual, with varying
      views about the delivery. Quality of relationships and competence of the
      administrator determined the best person to deliver the treatment. Heterogeneity
      in the intellectual disability population was a challenge to delivering manual
      based interventions. Participants made suggestions about language and
      organization. CONCLUSIONS: Amendments were made to the manual in line with expert
      feedback. An evaluation is warranted to test for feasibility, delivery,
      acceptability and efficacy.

PMID- 29573308
TI  - Synthesis of Non-Classical Arylated C-Saccharides through Nickel/Photoredox Dual
      Catalysis.
AB  - The development of synthetic tools to introduce saccharide derivatives into
      functionally complex molecules is of great interest, particularly in the field of
      drug discovery. Herein, we report a new route toward highly functionalized,
      arylated saccharides, which involves nickel-catalyzed cross-coupling of
      photoredox-generated saccharyl radicals with a range of aryl- and heteroaryl
      bromides, triggered by an organic photocatalyst. In contrast to existing methods,
      the mild reaction conditions achieve arylation of saccharide motifs while leaving
      the anomeric carbon available, thus providing access to a class of arylated
      glycosides that has been underexplored until now. To demonstrate the potential of
      this strategy in late-stage functionalization, a variety of structurally complex
      molecules incorporating saccharide moieties were synthesized.

PMID- 29573309
TI  - Survival of Mycobacterium avium subsp. paratuberculosis in the intermediate and
      final digestion products of biogas plants.
AB  - AIMS: To evaluate the survival of Mycobacterium avium subsp. paratuberculosis
      (MAP) during anaerobic digestion (AD), we studied two different biogas plants
      loaded with manure and slurry from paratuberculosis-infected dairy herds. METHODS
      AND RESULTS: Both plants were operating under mesophilic conditions, the first
      with a single digester and the second with a double digester. Mycobacterium avium
      subsp. paratuberculosis detection was performed by sampling each stage of the
      process, specifically the prefermenter, fermenter, liquid digestate and solid
      digestate stages, for 11 months. In both plants, MAP was isolated from the
      prefermenter stage. Only the final products, the solid and liquid digestates, of
      the one-stage plant showed viable MAP, while no viable MAP was detected in the
      digestates of the two-stage plant. CONCLUSIONS: Mycobacterium avium subsp.
      paratuberculosis showed a significant decrease during subsequent steps of the AD
      process, particularly in the two-stage plant. We suggest that the second digester
      maintained the digestate under anaerobic conditions for a longer period of time,
      thus reducing MAP survival and MAP load under the culture detection limit.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Our data are unable to exclude the presence
      of MAP in the final products of the biogas plants, particularly those products
      from the single digester; therefore, the use of digestates as fertilizers is a
      real concern related to the possible environmental contamination with MAP.

PMID- 29573310
TI  - Standing genetic diversity and selection at functional gene loci are associated
      with differential invasion success in two non-native fish species.
AB  - Invasive species are expected to experience a unique combination of high genetic
      drift due to demographic factors while also experiencing strong selective
      pressures. The paradigm that reduced genetic diversity should limit the
      evolutionary potential of invasive species, and thus, their potential for range
      expansion has received little empirical support, possibly due to the choice of
      genetic markers. Our goal was to test for effects of genetic drift and selection
      at functional genetic markers as they relate to the invasion success of two
      paired invasive goby species, one widespread (successful) and one with limited
      range expansion (less successful). We genotyped fish using two marker types:
      single nucleotide polymorphisms (SNPs) in known-function, protein-coding genes
      and microsatellites to contrast the effects of neutral genetic processes. We
      identified reduced allelic variation in the invaded range for the less successful
      tubenose goby. SNPs putatively under selection were responsible for the observed
      differences in population structure between marker types for round goby
      (successful) but not tubenose goby (less successful). A higher proportion of
      functional loci experienced divergent selection for round goby, suggesting
      increased evolutionary potential in invaded ranges may be associated with round
      goby's greater invasion success. Genes involved in thermal tolerance were
      divergent for round goby populations but not tubenose goby, consistent with the
      hypothesis that invasion success for fish in temperate regions is influenced by
      capacity for thermal tolerance. Our results highlight the need to incorporate
      functional genetic markers in studies to better assess evolutionary potential for
      the improved conservation and management of species.

PMID- 29573311
TI  - Secular trends in opportunistic infections, cancers and mortality in patients
      with AIDS during the era of modern combination antiretroviral therapy.
AB  - OBJECTIVES: The aim of the study was to estimate the incidence of, determine risk
      factors for, and investigate the consequences of opportunistic infections (OIs)
      and malignancies among patients with the acquired immune deficiency syndrome
      (AIDS) in the era of modern combination antiretroviral therapy (cART). METHODS:
      Three enrolment periods (1998-2002, 2003-2005 and 2006-2012), corresponding to
      changes in predominant cART regimens, were compared among 1889 participants
      enrolled in a prospective cohort study, the Longitudinal Study of Ocular
      Complications of AIDS (LSOCA). Incidences of AIDS-related OIs and cancers were
      estimated. Multivariate logistic and Cox regression models were used to determine
      the effect of demographic and clinical characteristics on OIs and mortality.
      RESULTS: Between participants enrolled in the 1998-2002 and 2006-2012 enrolment
      periods, the incidence of OIs decreased from 27 per 1000 person-years (PY) to 11
      per 1000 PY (P < 0.001), and mortality decreased from 41 per 1000 PY to 18 per
      1000 PY (P < 0.0001), corresponding to improvements in cART regimens.
      CONCLUSIONS: Improvements in cART regimens led to a progressive decline in the
      incidence of OIs and mortality between 1999 and 2013 among patients with AIDS in
      the era of modern cART.

PMID- 29573312
TI  - Loss to follow-up and mortality among HIV-infected adolescents receiving
      antiretroviral therapy in Pune, India.
AB  - OBJECTIVES: India has the highest number of HIV-infected adolescents in Asia, but
      little is known about their treatment outcomes. We assessed rates and factors
      associated with loss to follow-up (LTFU) and mortality among Indian adolescents.
      METHODS: The analysis included adolescents (10-19 years old) starting
      antiretroviral therapy (ART) between 2005 and 2014 at BJ Government Medical
      College, Pune, India. LTFU was defined as missing more than three consecutive
      monthly visits. The competing-risks method was used to calculate subdistribution
      hazard ratios (SHRs) of predictors for LTFU, with death as the competing risk.
      Cox proportional hazard models were used to identify predictors of mortality.
      RESULTS: Of 717 adolescents starting ART, 402 with complete data were included in
      the analysis. Of these, 61% were male and 80% were perinatally infected, and the
      median baseline CD4 count was 174 cells/MUL. LTFU and mortality rates were 4.4
      and 4.9/100-person years, respectively. Cumulative LTFU incidence increased from
      6% to 15% over 6 years. Age >= 15 years [adjusted SHR (aSHR) 2.44; 95% confidence
      interval (CI) 1.18-5.02] was a risk factor for LTFU. Cumulative mortality
      increased from 9.5% to 17.9% over 6 years. World Health Organization (WHO) stages
      III and IV [adjusted hazard ratio (aHR) 2.26; 95% CI: 1.14-4.48] and an increase
      in CD4 count by 100 cells/MUL (aHR: 0.59; 95% CI: 0.43-0.83) were associated with
      mortality. CONCLUSIONS: A third of adolescents had been lost to follow-up or died
      by follow-up year 6. Older age was a risk factor for LTFU and advanced clinical
      disease for death. Strategies to improve retention counselling for older
      adolescents and closer clinical monitoring of all adolescents must be considered.

PMID- 29573313
TI  - Combined In Situ Illumination-NMR-UV/Vis Spectroscopy: A New Mechanistic Tool in
      Photochemistry.
AB  - Synthetic applications in photochemistry are booming. Despite great progress in
      the development of new reactions, mechanistic investigations are still
      challenging. Therefore, we present a fully automated in situ combination of NMR
      spectroscopy, UV/Vis spectroscopy, and illumination to allow simultaneous and
      time-resolved detection of paramagnetic and diamagnetic species. This optical
      fiber-based setup enables the first acquisition of combined UV/Vis and NMR
      spectra in photocatalysis, as demonstrated on a conPET process. Furthermore, the
      broad applicability of combined UVNMR spectroscopy for light-induced processes is
      demonstrated on a structural and quantitative analysis of a photoswitch,
      including rate modulation and stabilization of transient species by temperature
      variation. Owing to the flexibility regarding the NMR hardware, temperature, and
      light sources, we expect wide-ranging applications of this setup in various
      research fields.

PMID- 29573314
TI  - New cytochalasin from Rosellinia sanctae-cruciana, an endophytic fungus of
      Albizia lebbeck.
AB  - AIM: To explore the potential of Rosellinia sanctae-cruciana an endophytic fungus
      associated with Albizia lebbeck for pharmaceutically important cytotoxic
      compounds. METHODS AND RESULTS: One novel cytochalasin, named jammosporin A (1)
      and four known analogues (2-5) were isolated from the culture of the endophytic
      fungus R. sanctae-cruciana, harboured from the leaves of the medicinal plant A.
      lebbeck. Their structures were elucidated by extensive spectroscopic analyses
      including one-dimensional and two-dimensional nuclear magnetic resonance data
      along with MS data and by comparison with literature reports. In preliminary
      screening the ethyl acetate extract of the fungal culture was tested for
      cytotoxic activity against a panel of four cancer cell lines (MOLT-4, A549, MIA
      PaCa-2 and MDA-MB-231), and found to be active against MOLT-4 with an IC50 value
      of 10 MUg ml-1 . Owing to the remarkable cytotoxic activity of the extract the
      isolated compounds (1-5) were evaluated for their cytototoxicity against the MOLT
      4 cell line by MTT assay. Interestingly, compounds 1-2, 4 and 5 showed
      considerable cytotoxic potential against the human leukaemia cancer cell line
      (MOLT-4) with IC50 values of 20.0, 10.0, 8.0 and 6.0 MUmol l-1 , respectively,
      while compound 3 showed an IC50 value of 25 MUmol l-1 . This is the first report
      of the existence of this class of secondary metabolites in R. sanctae-cruciana
      fungus. CONCLUSION: This study discovered a novel compound, named jammosporin A,
      isolated for the first time from R. sanctae-cruciana, an endophytic fungus of A.
      lebbeck with anticancer activity against the MOLT-4 cell line. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Rosellinia sanctae-cruciana represents an interesting source
      of a new compound with bioactive potential as a therapeutic agent against a human
      leukaemia cancer cell line (MOLT-4).

PMID- 29573315
TI  - Photochemical Formation of Cyclobutane Pyrimidine Dimers in DNA through Electron
      Transfer from a Flanking Base.
AB  - Electron transfer (ET) to a pyrimidine base from external moieties is a common
      step involved in the quenching or repair of the cyclobutane pyrimidine dimer
      (CPD). In contrast, we present a pathway that is initiated by an ET from a
      flanking guanine base to a pyrimidine base, leading to the formation of a CPD. We
      studied a T5mCG sequence with a methylated cytosine and our results demonstrate
      that the pathway involves the formation of an exciplex and intersystem crossings.
      This pathway also provides an explanation for why the mutational hot spots are
      correlated with the methylated CpG sequences, which has been a significant issue
      in cancer research.

PMID- 29573316
TI  - Risk factors of adverse events in endoscopic retrograde cholangiopancreatography
      for patients aged >=85 years.
AB  - AIM: Little is known about the factors that contribute to the occurrence of
      adverse events in endoscopic retrograde cholangiopancreatography (ERCP) for
      people aged >=85 years and safety for the super-old. Therefore, we decided to
      identify these factors and to examine whether ERCP is safe in the super-old.
      METHODS: This was a single-center retrospective study. A total of 137 patients
      aged >=85 years who underwent therapeutic ERCP at Chiba University Hospital from
      January 2012 to March 2017 were retrospectively reviewed. RESULTS: Four cases of
      Billroth II reconstruction and two cases of gastrectomy with Roux-en-Y
      reconstruction were excluded, and 131cases in total were examined in the present
      study. A total of 10 and 121 cases with and without adverse events, respectively,
      were present. Using univariate analysis, factors significantly contributing to
      the occurrence of adverse events in therapeutic ERCP were identified as aged >=90
      years (P = 0.0096), duodenal papilla cancer (P = 0.0012), gallbladder carcinoma
      (P = 0.023), and biliary metal stenting (P = 0.040). In multivariate analysis,
      only >=90 years-of-age was a significant factor (P = 0.049). In addition,
      comparison between 25 cases of the super-old and 106 cases aged 85-89 years was
      carried out. In the super-old group, the average value of the American Society of
      Anesthesiologists physical status classification and Charlson's Comorbidity Index
      were significantly better than those in 85-89-year-olds (P = 0.0035 and P <
      0.0001, respectively). CONCLUSIONS: Although the super-old group had fewer
      comorbid diseases, they had significantly increased adverse events compared with
      patients aged 85-89 years. Geriatr Gerontol Int 2018; 18: 1038-1045.

PMID- 29573317
TI  - Oxygen uptake efficiency slope during exercise in adults with Down syndrome.
AB  - BACKGROUND: Persons with Down syndrome (DS) have low aerobic exercise capacity.
      The present authors sought to compare the oxygen uptake efficiency slope (OUES)
      between adults with and without DS performing graded exercise testing (GXT) and
      to investigate its relationship with peak oxygen uptake (VO2peak ) in both groups
      of participants. METHOD: Twenty-three participants with DS and 24 non-disabled
      controls performed GXT with VO2 measurements. OUES was calculated from data of
      the first 75%, 90% and 100% GXT time. Multiple linear regression analyses were
      computed to explore associations between the independent (OUES and DS) and the
      dependent variables (VO2peak ). RESULTS: VO2peak , GXT time and OUES were lower
      in participants with DS (p < .05). OUES and DS explained 69.3% of the variance in
      VO2peak . CONCLUSIONS: Our findings show that OUES values are lower in persons
      with DS. Additionally, it was shown that OUES has predictive value for VO2peak
      estimations in DS.

PMID- 29573318
TI  - Work scheme to isolate the different micro-organisms found in hydrogen-producing
      reactors: a study of effectiveness by pyrosequencing analysis.
AB  - AIM: The aim of this research was to create a work scheme for the isolation of
      the different micro-organisms commonly found in hydrogen-producing reactors and
      to test its effectiveness. METHODS AND RESULTS: Methods were selected to isolate
      anaerobic spore-forming fermenters, anaerobic fermenters that do not form spores,
      facultative aerobic fermenters and lactic acid bacteria. The methods were tested
      in two samples taken from a hydrogen-producing reactor fed with cheese whey. 16S
      rRNA gene sequences from isolates were compared with pyrosequencing analysis from
      the same samples. The isolates represented more than 88% of the abundance
      detected by pyrosequencing. Organisms from the genera Clostridium, Rahnella,
      Megasphaera, Lactobacillus, Propionibacterium, Bifidobacterium, Chryseobacterium
      and Acetobacter were isolated. Hydrogen-producing capacity was confirmed for the
      Clostridium, Rahnella and Megasphaera isolates. Coculture experiments indicate
      that Megasphaera prevented the total inhibition of Clostridium by Lactobacillus.
      CONCLUSION: The work scheme proposed was effective to isolate most of the micro
      organisms detected by pyrosequencing analysis. Physiological studies suggested a
      key role of Megasphaera. SIGNIFICANCE AND IMPACT OF THE STUDY: We showed the high
      culturability of the microbial communities from hydrogen-producing bioreactors.
      The isolates can be used to perform physiological studies to understand the H2 
      producing process.

PMID- 29573319
TI  - The Chemistry behind Catechol-Based Adhesion.
AB  - The adhesion of some marine organisms to almost any kind of surface in wet
      conditions has aroused increasing interest in recent decades. Numerous
      fundamental studies have been performed to understand the scientific basis of
      this behaviour, with catechols having been found to play a key role. Several
      novel bio-inspired adhesives and coatings with value-added performances have been
      developed by taking advantage of the knowledge gained from these studies. To date
      there has been no detailed overview focusing exclusively on the complex mode of
      action of these materials. The aim of this Review is to present recent
      investigations that elucidate the origin of the strong and versatile adsorption
      capacities of the catechol moiety and the effects of extrinsic factors that play
      important roles in the overall adhesion process, such as pH value, solvent, and
      the presence of metal ions. The aim is to detail the chemistry behind the
      astonishing properties of natural and synthetic catechol-based adhesive
      materials.

PMID- 29573320
TI  - Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in
      a multicentre cohort of patients with suppressed HIV-1 replication.
AB  - OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine +
      dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with
      undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and
      virological failure (VF) and their predictors were assessed in a multicenter
      cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after
      reaching viral suppression. Secondary objective was the evaluation of changes in
      lipid profile, renal and immunological functions at week 48. RESULTS: We enrolled
      206 patients (72.8% male, with 51 years median age), who mainly switched their
      antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The
      estimated probability of maintaining virological suppression at 48 and 96 weeks
      was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative
      time on antiretroviral therapy. The estimated probability of remaining on
      lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively.
      A significant improvement in immunological function (CD4 count and CD4/CD8 ratio)
      was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio,
      triglycerides and estimated glomerular filtration rate. CONCLUSIONS: Lamivudine
      plus dolutegravir was effective in maintaining viral suppression in our cohort
      and led to an improvement in metabolic and immunologic functions.

PMID- 29573321
TI  - From Solute, Fluidic and Particulate Precursors to Complex Organizations of
      Matter.
AB  - The organization of matter from its constitutive units recruits intermediate
      states with distinctive degrees of self-association and molecular order. Existing
      as clusters, droplets, gels as well as amorphous and crystalline nanoparticles,
      these precursor forms have fundamental contributions towards the composition and
      structure of inorganic and organic architectures. In this personal account, we
      show that the transitions from atoms, molecules or ionic species to
      superstructures of higher order are intertwined with the interfaces and
      interactions of precursor and intermediate states. Structural organizations
      distributed across different length scales are explained by the multistep nature
      of nucleation and crystallization, which can be guided towards functional hybrid
      materials by the strategic application of additives, templates and reaction
      environments. Thus, the non-classical pathways for material formation and growth
      offer conceptual frameworks for elucidating, inducing and directing fascinating
      material organizations of biogenic and synthetic origins.

PMID- 29573322
TI  - Wearable Platform for Real-time Monitoring of Sodium in Sweat.
AB  - A fully integrated and wearable platform for harvesting and analysing sweat
      sodium concentration in real time during exercise has been developed and tested.
      The platform was largely produced using 3D printing, which greatly simplifies
      fabrication and operation compared to previous versions generated with
      traditional production techniques. The 3D printed platform doubles the capacity
      of the sample storage reservoir to about 1.3 ml, reduces the assembly time and
      provides simple and precise component alignment and contact of the integrated
      solid-state ion-selective and reference electrodes with the sorbent material. The
      sampling flowrate in the device can be controlled by introducing threads to
      enhance wicking of sweat from the skin, across the electrodes to the storage
      area. The platform was characterised in the lab and in exercise trials over a
      period of about 60 minutes continuous monitoring. Sweat sodium concentration was
      found to rise initially to approximately 17 mM and decline gradually over the
      period of the trial to about 11-12 mM.

PMID- 29573323
TI  - The interaction of the Chrna5 D398N variant with developmental nicotine exposure.
AB  - A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an
      aspartic acid [D] to asparagine [N] at position 398 of the human alpha5 nicotinic
      acetylcholine receptor subunit) has been associated with increased risk for
      nicotine dependence. Consequently, carriers of the risk variant may be at
      elevated risk for in utero nicotine exposure. To assess whether this gene
      environment interaction might impact nicotine intake in developmental nicotine
      exposed offspring, we utilized a mouse expressing this human SNP. D and N dams
      drank nicotine (100 MUg/mL) in 0.2% saccharin water or 0.2% saccharin water alone
      (vehicle) as their sole source of fluid from 30 days prior to breeding until
      weaning of offspring. The nicotine (D Nic, N Nic) or vehicle (D Veh, N Veh)
      exposed offspring underwent a 2-bottle choice test between postnatal ages of 30
      to 46 days. N Nic offspring consumed the most nicotine at the highest
      concentration (400 MUg/mL) compared with all other groups. In contrast, D Nic
      offspring drank the least amount of nicotine at all concentrations tested.
      Nicotine-stimulated dopamine (DA) release measured from striatal synaptosomes was
      increased in D Nic offspring, while decreased in N Nic offspring relative to
      their genotype-matched controls. These data suggest that the alpha5 variant
      influences the effect of developmental nicotine exposure on nicotine intake of
      exposed offspring. This gene-environment interaction on striatal DA release may
      provide motivation for increased nicotine seeking in N Nic offspring and reduced
      consumption in D Nic offspring.

PMID- 29573325
TI  - Postharvest processing decreases the richness of bacterial taxa in the
      phyllosphere of broccoli.
AB  - AIMS: Diverse bacterial communities residing on the surfaces of fresh vegetables
      are important for food quality and safety; however, knowledge of the phyllosphere
      microbiota on fresh vegetables and of how it changes during postharvest stage is
      poorly understood. METHODS AND RESULTS: We used culturing to quantify bacterial
      abundance and 16S rRNA 454 pyrosequencing to analyse the bacterial community
      composition on broccoli florets collected from farms (preharvest) and retail
      stores (postharvest). The bacterial community compositions of the preharvest and
      postharvest broccoli were significantly different. The number of non-Escherichia
      coli coliform bacteria (Hafnia sp. and Rahnella sp.) was higher in the
      postharvest broccoli than in the preharvest broccoli. Minor bacterial taxa at the
      phylum and genus levels had markedly disappeared in the postharvest broccoli,
      resulting in low bacterial species richness in the postharvest broccoli.
      CONCLUSIONS: The dominant bacterial taxa persist and prevail in the phyllosphere
      of broccoli during the postharvest stage. SIGNIFICANCE AND IMPACT OF THE STUDY: A
      popular crop of leafy vegetables, broccoli, is of great agricultural and
      nutritional importance. This study provides a detailed description of changes in
      the bacterial community of broccoli in harvest and storage. This study presents
      novel data on the impact of postharvest conditions on the bacterial populations
      on broccoli florets.

PMID- 29573326
TI  - Platelets loaded with liposome-encapsulated thrombin have increased
      coagulability.
AB  - : Essentials Platelet transfusions can have limited efficacy during hemorrhage
      associated with coagulopathy. Thrombin can be shielded by encapsulation into
      nanoliposomes and delivered to platelets ex vivo. Loading platelets with
      liposomal thrombin improved several aspects of platelet coagulability. Platelets
      loaded with liposomal thrombin can overcome some coagulopathic deficiencies in
      vitro. SUMMARY: Background Platelets are integral to clot formation and are often
      transfused to stop or prevent bleeding. However, transfusions of platelets are
      not always effective, particularly in the most severe cases of hemorrhage.
      Nanoparticle systems have been developed to mimic platelets but inherently lack
      important aspects of platelet function, which limits their potential
      effectiveness. Objectives Increasing the natural coagulability of transfusable
      platelets could increase their efficacy during treatment of severe hemorrhage.
      Thrombin is a potent platelet agonist that currently cannot be used intravenously
      because of the risk of thrombosis. We hypothesized that delivery of thrombin to
      ex vivo platelets via liposomal encapsulation would enable transfusable platelets
      to become more coagulable in response to platelet agonists. Methods Thrombin was
      encapsulated into nanoliposomes and delivered to platelets ex vivo. Platelet
      coagulability was measured by monitoring platelet activation, clot contraction,
      clot time and clot stability in several in vitro assays. These parameters were
      also measured under conditions where coagulation is compromised, including during
      acidosis, antiplatelet drugs, hemophilia A and trauma-induced coagulopathy.
      Results Liposomal thrombin was endocytosed and used by platelets ex vivo but was
      not secreted upon activation. These modified platelets became more sensitive and
      responsive to agonists and improved clotting time even under conditions that
      normally cause platelet dysfunction or have impaired coagulation. Conclusions
      Several aspects of platelet function were enhanced by ex vivo delivery of
      liposomal thrombin.

PMID- 29573324
TI  - The African turquoise killifish: A research organism to study vertebrate aging
      and diapause.
AB  - The African turquoise killifish has recently gained significant traction as a new
      research organism in the aging field. Our understanding of aging has strongly
      benefited from canonical research organisms-yeast, C. elegans, Drosophila,
      zebrafish, and mice. Many characteristics that are essential to understand aging
      for example, the adaptive immune system or the hypothalamo-pituitary axis-are
      only present in vertebrates (zebrafish and mice). However, zebrafish and mice
      live more than 3 years and their relatively long lifespans are not compatible
      with high-throughput studies. Therefore, the turquoise killifish, a vertebrate
      with a naturally compressed lifespan of only 4-6 months, fills an essential gap
      to understand aging. With a recently developed genomic and genetic toolkit, the
      turquoise killifish not only provides practical advantages for lifespan and
      longitudinal experiments, but also allows more systematic characterizations of
      the interplay between genetics and environment during vertebrate aging.
      Interestingly, the turquoise killifish can also enter a long-term dormant state
      during development called diapause. Killifish embryos in diapause already have
      some organs and tissues, and they can last in this state for years, exhibiting
      exceptional resistance to stress and to damages due to the passage of time.
      Understanding the diapause state could give new insights into strategies to
      prevent the damage caused by aging and to better preserve organs, tissues, and
      cells. Thus, the African turquoise killifish brings two interesting aspects to
      the aging field-a compressed lifespan and a long-term resistant diapause state,
      both of which should spark new discoveries in the field.

PMID- 29573327
TI  - Imaging of non-accidental injury; what is clinical best practice?
AB  - Non-accidental injury (NAI) remains the leading cause of morbidity and mortality
      in children. Fractures are the second most common findings of NAI, after
      cutaneous lesions such as bruises and contusions. Imaging in NAI remains a
      controversial issue with little agreement concerning how, when and what imaging
      modalities should be used in the investigation of suspected cases. This review
      addresses the radiological investigations and findings of NAI, and the
      differential diagnoses of these findings. Adherence to the international
      guidelines for skeletal survey imaging is recommended. This ensures the content
      and quality of the radiographic series are of an optimal standard to improve the
      detection of occult fractures, and ensuring the accurate reporting of images. The
      involvement of a paediatric radiologist is important, if not essential in the
      diagnosis of NAI. In the evaluation of suspected cases, the role of the
      radiologist includes the detection of radiological findings suggestive of NAI,
      and the differentiation of these findings from normal variants and underlying
      pathologies. The diagnosis of NAI relies not only on radiological imaging, but
      also a combination of clinical and social findings. It is mandatory that all
      physicians work in close collaboration to improve diagnostic accuracy, as failure
      to diagnose NAI carries significant risk for morbidity.

PMID- 29573328
TI  - Kidney transplant graft outcomes in 379 257 recipients on 3 continents.
AB  - Kidney transplant outcomes that vary by program or geopolitical unit may result
      from variability in practice patterns or health care delivery systems. In this
      collaborative study, we compared kidney graft outcomes among 4 countries (United
      States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed
      transplant and follow-up registry data from 1988-2014 for 379 257 recipients of
      first kidney-only transplants using Cox regression. Compared to the United
      States, 1-year adjusted graft failure risk was significantly higher in the United
      Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18-1.26, P <
      .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14
      1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84-0.96, P = .001). In
      contrast, long-term adjusted graft failure risk (conditional on 1-year function)
      was significantly higher in the United States compared to Australia, New Zealand,
      and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001).
      Thus long-term kidney graft outcomes are approximately 25% worse in the United
      States than in 3 other countries with well-developed kidney transplant systems.
      Case mix differences and residual confounding from unmeasured factors were found
      to be unlikely explanations. These findings suggest that identification of
      potentially modifiable country-specific differences in care delivery and/or
      practice patterns should be sought.

PMID- 29573329
TI  - A novel HLA class I allele: HLA-A*11:01:49.
AB  - The HLA-A*11:01:49 allele differs from A*11:01:01:01 by one synonymous nucleotide
      substitution at position 837.

PMID- 29573331
TI  - Facile Ionic Liquid-Assisted Strategy for Direct Precipitation of Eu2+ -Activated
      Nanophosphors under Ambient Conditions.
AB  - This work describes a novel ionic liquid (IL)-assisted synthesis strategy for a
      direct and easy production of Eu2+ -doped nanoparticles (NPs), where ILs are also
      used as fluoride sources to avoid the use of elemental fluorine or toxic
      hydrofluoric acid. Up to now, the direct synthesis of Eu2+ -doped nanophosphors
      consisted of an enormous challenge, due to the oxidation to Eu3+ observed in
      hydrous solution, which is commonly used for the preparation of NPs, generating
      lattice defects and undesired particle growth or agglomeration by additional
      reducing steps at high temperatures. In contrast, ILs, unless containing ClO4- or
      NO3- anions, do not present an oxidizing character, allowing the direct
      precipitation of NPs, e.g., using Eu2+ containing starting materials. Here, the
      undoped and Eu2+ -doped BaFCl NPs have been prepared under atmospheric conditions
      for the first time using ILs as solvents and also as fluoride source, applying
      sonochemical and microwave-assisted approaches. In general, this method bears an
      enormous potential for an easy synthesis of fluoride materials compared to
      inconvenient solid-state methods. In addition, the IL plays the role of a
      strongly attached protecting shell which represents ~7-8% of the total NPs
      weight.

PMID- 29573332
TI  - Epidemiology of multiple myeloma in 17 Latin American countries: an update.
AB  - The objective of this study was to describe incidence, mortality rates, and
      trends for multiple myeloma (MM) in Latin America (LA), contributing to better
      knowledge on the epidemiology of MM in this continent. Incidence data were
      extracted from the International Agency for Research on Cancer (IARC), for the
      period 1990-2007. Mortality data were obtained for 17 countries from the World
      Health Organization, for the period 1995-2013. Annual average percentage change
      (AAPC) and 95% confidence interval (95% CI) were calculated for incidence and
      mortality. The average incidence rate of MM was higher in Cali (Colombia). For
      the age-group over 60 years old, rates were 14.2 and 12.8 per 100,000 inhabitants
      for men and women, respectively. Increasing incidence trends were verified for
      Cali (Colombia). Mortality rates were higher among men; most countries presented
      increasing trends, and the highest increments were observed in Guatemala (12.5%
      [95% CI: 10.6; 14.5] in men; 8.8% [95% CI: 7.8; 9.8] in women), Ecuador (5.5%
      [95% CI: 5.0; 6.0] in men; 3.7 [95% CI: 3.1; 4.3] in women), Paraguay (2.9% [95%
      CI: 2.3; 3.5] in men; 3.2% [95% CI: 2.1; 4.3] in women), and Brazil (1.4% [95%
      CI: 1.3; 1.5] in men; 0.9% [95% CI: 0.8; 1.0] in women). Multiple myeloma
      presented heterogeneous incidence patterns in Cali (Colombia), Quito (Ecuador),
      and Costa Rica. Increasing mortality trends were verified for most Latin American
      countries and could be related to limited access to diagnosis and new therapies.

PMID- 29573333
TI  - Self-care among older people living with chronic conditions.
AB  - PURPOSE: The aim of this study was to clarify the concept of self-care among
      older people living with chronic health conditions. This concept clarification
      will assist nurses in addressing self-care among older people through research,
      policy and practice in offering an expanded conceptual model. BACKGROUND: Several
      policy influences over the past decade directly relate to the increased
      importance and economic necessity to require self-directed care for older people
      living with chronic health conditions to maintain their care at home in the
      community. METHOD: A selective review of literature on the concept of self-care
      included 31 sources. The Norris Concept Clarification method (1982) was used for
      clarification. The phenomenon is described historically according to its
      antecedents, attributes and consequences. RESULTS: A proposed definition is
      provided based on the clarification of this concept. A conceptual model is
      presented through an ecological framework. Self-care among older people living
      with chronic conditions is multidimensional and has multilevel influences
      (individual, community, system levels) and is mediated by the contexts and
      processes of ageing. Self-care originates along one's life course and is learned.
      Self-care responses are based on care needs when living with chronic health
      conditions. CONCLUSION: Self-care is an individual capacity, disposition and
      activity older people manifest in living with multiple chronic conditions. These
      features (capacity, disposition, action) influence one another and are
      hierarchical and continuous. Research, practice and policies that promote self
      care among older people can focus on these features to improve health outcomes
      and promote new models of care consistent with personal development and chronic
      care needs in older age. IMPLICATIONS FOR PRACTICE: This concept clarification
      can offer a model to support self-care among older people living with chronic
      conditions.

PMID- 29573330
TI  - Clinically relevant bleeding in cancer patients treated for venous
      thromboembolism from the CATCH study.
AB  - : Essentials Cancer patients receiving anticoagulants for venous thromboembolism
      have an elevated bleeding risk. This secondary analysis of CATCH assessed
      characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of
      cancer patients with thrombosis using therapeutic doses of anticoagulation. After
      multivariate analysis, risk factors for CRB were age >75 years and intracranial
      malignancy. SUMMARY: Background Cancer patients with acute venous thromboembolism
      (VTE) receiving anticoagulant treatment have an increased bleeding risk.
      Objectives We performed a prespecified secondary analysis of the randomized, open
      label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and
      the risk factors for clinically relevant bleeding (CRB). Patients/Methods
      Patients with active cancer and acute, symptomatic VTE received either tinzaparin
      175 IU kg-1 once daily or warfarin (target International Normalized Ratio [INR]
      of 2.0-3.0) for 6 months. Fisher's exact test was used to screen prespecified
      clinical risk factors; those identified as being significantly associated with an
      increased risk of CRB then underwent competing risk regression analysis of time
      to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB
      events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78
      patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95%
      confidence interval [CI] 0.45-0.89). Common bleeding sites were gastrointestinal
      (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In
      multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83,
      95% CI 1.14-2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07-3.62). In the
      warfarin group, 40.4% of CRB events occurred in patients with with an INR of <
      3.0. A lower time in therapeutic range was associated with a higher risk of CRB.
      Conclusions CRB is a frequent complication in cancer patients with VTE during
      anticoagulant treatment, and is associated with age > 75 years and intracranial
      malignancy.

PMID- 29573334
TI  - FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and
      colorectal cancers in vitro.
AB  - Although regorafenib has demonstrated survival benefits in patients with
      metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker
      has been identified for predicting sensitivity to regorafenib. Here, we
      investigated preclinical activity of regorafenib in gastric and colorectal cancer
      cells to identify genetic alterations associated with sensitivity to regorafenib.
      Mutation profiles and copy number assays of regorafenib target molecules
      indicated that amplification of fibroblast growth factor receptor 2 (FGFR2) was
      the only genetic alteration associated with in vitro sensitivity to regorafenib.
      Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream
      signaling molecules in a dose-dependent manner and selectively in FGFR2-amplified
      cells. Regorafenib induced G1 arrest (SNU-16, KATO-III) and apoptosis (NCI-H716);
      however, no significant changes were seen in cell lines without FGFR2
      amplification. In SNU-16 mice xenografts, regorafenib significantly inhibited
      tumor growth, proliferation, and FGFR signaling compared to treatment with
      control vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in
      FGFR2-amplified gastric and colorectal cancer and, therefore, might be considered
      for integration into treatment in patients with FGFR2-amplified gastric and
      colorectal cancers.

PMID- 29573335
TI  - Posttransplant reduction in preexisting donor-specific antibody levels after
      belatacept- versus cyclosporine-based immunosuppression: Post hoc analyses of
      BENEFIT and BENEFIT-EXT.
AB  - BENEFIT and BENEFIT-EXT were phase III studies of cytotoxic T-cell crossmatch
      negative kidney transplant recipients randomized to belatacept more intense (MI)
      based, belatacept less intense (LI)-based, or cyclosporine-based
      immunosuppression. Following study completion, presence/absence of HLA-specific
      antibodies was determined centrally via solid-phase flow cytometry screening.
      Stored sera from anti-HLA-positive patients were further tested with a single
      antigen bead assay to determine antibody specificities, presence/absence of donor
      specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs
      present. The effect of belatacept-based and cyclosporine-based immunosuppression
      on MFI was explored post hoc in patients with preexisting DSAs enrolled to
      BENEFIT and BENEFIT-EXT. In BENEFIT, preexisting DSAs were detected in 4.6%,
      4.9%, and 6.3% of belatacept MI-treated, belatacept LI-treated, and cyclosporine
      treated patients, respectively. The corresponding values in BENEFIT-EXT were
      6.0%, 5.7%, and 9.2%. In both studies, most preexisting DSAs were of class I
      specificity. Over the first 24 months posttransplant, a greater proportion of
      preexisting DSAs in belatacept-treated versus cyclosporine-treated patients
      exhibited decreases or no change in MFI. MFI decline was more apparent with
      belatacept MI-based versus belatacept LI-based immunosuppression in both studies
      and more pronounced in BENEFIT-EXT versus BENEFIT. Although derived post hoc,
      these data suggest that belatacept-based immunosuppression decreases preexisting
      DSAs more effectively than cyclosporine-based immunosuppression.

PMID- 29573336
TI  - Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases.
AB  - The 2016 Global Burden of Disease report by WHO revealed that diseases of the
      gastrointestinal tract (GIT) had one of the highest incidence rates worldwide.
      The plethora of factors that contribute to the development of GIT-related
      illnesses can be divided into genetic, environmental and lifestyle factors. Apart
      from that, the role that infectious agents play in the development of GIT
      diseases has piqued the interest of researchers worldwide. The human gut harbors
      approximately 1014 bacteria in it with increasing concentration toward the lower
      GIT. Among the various microbiota that colonize the human gut, Gram-negative
      bacteria have been most notoriously linked to GIT-related diseases such as
      inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis
      and colorectal cancer (CRC). Some of the notable culprits that have been
      attributed to these diseases are Bacteroides fragilis, Fusobacterium nucleatum,
      Escherichia coli and Helicobacter pylori. However, studies in recent years are
      beginning to recognize a new player, Klebsiella pneumoniae (K. pneumoniae) in the
      causation and progression of GIT diseases. Once synonymous with infections and
      diseases of the upper respiratory tract, K. pneumoniae has now emerged as one of
      the pathogens commonly isolated from patients with GIT diseases. However,
      extensive studies attributing K. pneumoniae to GIT diseases, particularly that of
      CRC are scanty. Therefore, this review intends to shed light on the association
      of K. pneumoniae in gastrointestinal diseases such as Crohn's disease, ulcerative
      colitis as well as CRC.

PMID- 29573337
TI  - Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests
      are better than conventional osmotic fragility tests for the diagnosis of
      hereditary spherocytosis.
AB  - INTRODUCTION: Hereditary spherocytosis (HS) is the most common inherited
      hemolytic anemia with heterogeneous clinico-laboratory manifestations. We
      evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric
      osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT)
      for the diagnosis of hereditary spherocytosis (HS). METHODS: One hundred two
      suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room
      temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA)
      were included, and performance of the above 4 tests was evaluated. For EMA and
      FOFT, 5 normal controls were assessed together with the patients and cutoffs were
      calculated using receiver-operator-characteristics curve (ROC) analysis. RESULTS:
      The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells
      (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%,
      respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow
      cytometric tests performed better. Sensitivity and specificity of EMA was 86.2%
      and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The
      combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of
      100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the
      severity of the disease while %EMA decrease and %RRC did not correlate with
      severity of the disease. CONCLUSION: Flow-cytometric osmotic fragility test is
      the best possible single test followed by EMA for diagnosis of HS. A combination
      of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to
      replace conventional OFTs in future.

PMID- 29573338
TI  - Nanodiamonds and Their Applications in Cells.
AB  - Diamonds owe their fame to a unique set of outstanding properties. They combine a
      high refractive index, hardness, great stability and inertness, and low
      electrical but high thermal conductivity. Diamond defects have recently attracted
      a lot of attention. Given this unique list of properties, it is not surprising
      that diamond nanoparticles are utilized for numerous applications. Due to their
      hardness, they are routinely used as abrasives. Their small and uniform size
      qualifies them as attractive carriers for drug delivery. The stable fluorescence
      of diamond defects allows their use as stable single photon sources or biolabels.
      The magnetic properties of the defects make them stable spin qubits in quantum
      information. This property also allows their use as a sensor for temperature,
      magnetic fields, electric fields, or strain. This Review focuses on applications
      in cells. Different diamond materials and the special requirements for the
      respective applications are discussed. Methods to chemically modify the surface
      of diamonds and the different hurdles one has to overcome when working with
      cells, such as entering the cells and biocompatibility, are described. Finally,
      the recent developments and applications in labeling, sensing, drug delivery,
      theranostics, antibiotics, and tissue engineering are critically discussed.

PMID- 29573339
TI  - Empowering education of arthroplasty patients' significant others in three
      Southern European countries.
AB  - AIMS AND OBJECTIVES: To examine the relationship between significant others'
      expected and received knowledge and their background characteristics in three
      Mediterranean countries (Cyprus, Greece, Spain), all of which deal with economic
      restrictions, have similar social support systems with the family members acting
      as family caregivers, and cultural similarities. BACKGROUND: Significant others'
      role is a key element in the older patients' postoperative recovery. However,
      people who take care of persons older than 65 years, as persons undergoing
      arthroplasty, are usually old themselves and need special support. DESIGN:
      Multicentre, descriptive, correlational study. METHODS: Data were collected
      preoperatively from 189 and postoperatively from 185 significant others using the
      Knowledge Expectations and the Received Knowledge of Significant Others Scales
      during 2010-2012. RESULTS: Approximately one-fourth of the significant others
      were older than 65 years. Their knowledge expectations were not adequately
      addressed in any of the countries; they expected to be educated more on
      biophysiological issues and received the lowest knowledge regarding financial
      issues. The highest difference between expected and received knowledge was found
      in Greece and the lowest in Cyprus. Significant others may be less prepared for
      dealing with situations at home due to the knowledge difference between expected
      and received knowledge. CONCLUSIONS: Significant others receive less education
      comparing to what they expect; therefore, they are not prepared for dealing with
      problematic situations during their old relative's recovery. This is especially
      important in Mediterranean countries, where family members often provide patient
      care. IMPLICATIONS FOR PRACTICE: As health care is changing towards active
      participation of patients and family, it is important that nurses provide the
      education needed, as lower education may lead to poor patient outcomes and higher
      education may lead to significant others' anxiety. Nurses may keep in mind that
      older significant others do not report higher knowledge difference, but may have
      lower expectations.

PMID- 29573340
TI  - The adsorption of dabigatran is as efficient as addition of idarucizumab to
      neutralize the drug in routine coagulation assays.
AB  - INTRODUCTION: The direct thrombin inhibitor dabigatran interferes with
      thrombophilia screening and with the diagnosis of hemostasis disorders that
      develop during treatment with the anticoagulant. In vitro addition of
      idarucizumab, a humanized antibody fragment that binds dabigatran, to plasma
      samples containing dabigatran fully neutralizes the drug. This study was carried
      out to determine whether binding of dabigatran on selected insoluble commercial
      adsorbent material, DOAC-STOPR , was as efficient as idarucizumab to neutralize
      the anticoagulant activity of the drug in vitro. METHODS: Coagulation assays
      sensitive to dabigatran were carried out with patient and control plasma samples
      spiked with dabigatran and supplemented with idarucizumab or incubated with
      adsorbent material. RESULTS: In samples containing upto 10 000 ng/mL dabigatran,
      the adsorption procedure was at least as efficient as the addition of
      idarucizumab to neutralize the activity of the anticoagulant drug. Neither the
      adsorption procedure nor the addition of idarucizumab did impair routine
      coagulation assays carried out with plasma devoid of dabigatran, such as the
      activated partial thromboplastin time, prothrombin time, fibrinogen Clauss, and
      the thrombophilia screening assays used to detect antiphospholipid antibodies or
      activated protein C resistance. In addition, the adsorption procedure did not
      interfere with the detection of lupus anticoagulant samples. CONCLUSIONS:
      Adsorption of dabigatran in plasma samples containing the drug neutralizes its
      activity as efficiently as the addition of idarucizumab. This method allows the
      evaluation of thrombophilia markers without interruption of anticoagulation
      therapy or the detection of hemostasis disorders in patients treated with the
      drug.

PMID- 29573341
TI  - A Modular System for the Design of Stimuli-Responsive Multifunctional
      Nanoparticle Aggregates by Use of Host-Guest Chemistry.
AB  - A self-assembly approach for the design of multifunctional nanomaterials
      consisting of different nanoparticles (gold, iron oxide, and lanthanide-doped
      LiYF4 ) is developed. This modular system takes advantage of the light-responsive
      supramolecular host-guest chemistry of beta-cyclodextrin and arylazopyrazole,
      which enables the dynamic and reversible self-assembly of particles to spherical
      nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide
      nanoparticles, the aggregates can be manipulated by an external magnetic field
      leading to the formation of linear structures. As a result of the integration of
      upconversion nanoparticles, the aggregates are additionally responsive to near
      infrared light and can be redispersed by use of the upconversion effect. By
      varying the nanoparticle and linker concentrations the composition, size, shape,
      and properties of the multifunctional nanoparticle aggregates can be fine-tuned.

PMID- 29573342
TI  - Prenatal diet and children's trajectories of hyperactivity-inattention and
      conduct problems from 3 to 8 years: the EDEN mother-child cohort.
AB  - BACKGROUND: Evidence shows that diet contributes substantially to lifelong
      physical and mental health. Although dietary exposure during gestation and early
      postnatal life is critical, human epidemiological data are limited regarding its
      link with children's subsequent externalizing issues. The aim of this study was
      to investigate the role of maternal diet during pregnancy in offspring's symptoms
      of hyperactivity-inattention and conduct problems from ages 3 to 8 years.
      METHODS: We used data of 1,242 mother-child pairs from a French cohort followed
      up from pregnancy until the children were 8 years of age. Dietary patterns (DP)
      of the mother during pregnancy were assessed with food frequency questionnaires.
      Children's externalizing behavior was assessed with the Strength and Difficulties
      Questionnaire at ages 3, 5, and 8 years, from which trajectories of hyperactivity
      inattention symptoms and conduct problems were derived. We conducted
      multivariable logistic models to study associations adjusted for a range of
      potential confounders. RESULTS: Results showed significant relationships between
      maternal 'low Healthy diet' (adjusted Odds Ratio (aOR) = 1.61; IC 95%: 1.09-2.37)
      and 'high Western diet' (aOR = 1.67; IC 95%: 1.13-2.47) during pregnancy and
      children's trajectories of high symptoms of hyperactivity-inattention. The
      associations took into account relevant confounders such as DP of the children at
      age 2 years, maternal stress and depression, gestational diabetes, and
      socioeconomic variables. CONCLUSIONS: Maternal diet during pregnancy was
      independently associated with children's hyperactivity-inattention symptoms but
      not with conduct problems. Early prevention addressing lifestyle should
      specifically target diet in pregnant women.

PMID- 29573344
TI  - Changes in inflammation and insulin pathways mediate the association between
      resistance training and breast cancer survival.

PMID- 29573343
TI  - Reference intervals for plasma cystatin C and plasma creatinine in adults using
      methods traceable to international calibrators and reference methods.
AB  - INTRODUCTION: The aim of this study was to establish reference intervals for
      plasma cystatin C and creatinine in adults using the Gentians cystatin C method
      traceable to the international calibrator standard ERM-DA471/IFCC and a
      creatinine method traceable to the IDMS (Isotope Dilution Mass Spectrometry)
      creatinine reference method. METHODS: Blood samples were collected from 304
      healthy blood donors (152 men and 152 women between 17 and 66 years old) with 30
      31 men and 30-31 women in each ten-year interval. Plasma cystatin C was analyzed
      using the Gentian Cystatin C assay on a Roche cobas c702 analyzer, and plasma
      creatinine was analyzed using the CREA Plus assay on the Roche Modular P
      analyzer. RESULTS: The nonparametric reference intervals for plasma cystatin C
      were 0.58-1.00 mg/L in women (median 0.78 mg/L, range 0.56-1.06 mg/L) and 0.62
      1.04 mg/L in men (median 0.79 mg/L, range 0.61-1.07 mg/L). The Mann-Whitney U
      test revealed no gender-related difference in plasma cystatin C (P = .21). A
      common reference interval in women and men was calculated to be 0.61-1.01 mg/L
      (median 0.79 mg/L, range 0.56-1.07 mg/L). The nonparametric reference interval
      for plasma creatinine was 52-89 MUmol/L in women (median 69 MUmol/L, range 52-92
      MUmol/L) and 61-108 MUmol/L in men (median 86 MUmol/L, range 56-118 MUmol/L). The
      Mann-Whitney U test revealed a gender-related difference in plasma creatinine (P
      < .0001). CONCLUSION: In conclusion, we have established reference intervals for
      plasma cystatin C and creatinine in adults using methods traceable to
      international standards.

PMID- 29573345
TI  - Do clinical characteristics predict the cognitive course in early-onset
      schizophrenia-spectrum disorders?
AB  - BACKGROUND: Being in a period with extensive brain maturation, adolescents with
      early-onset schizophrenia-spectrum disorders (EOS) provide unique
      neurodevelopmental data that may contribute to a better understanding of
      schizophrenia at all ages. Cognitive dysfunction is a central feature of
      schizophrenia and is more pronounced in EOS than in later onset illness. However,
      there is limited research on both the long-term course of global cognition in
      EOS, and how cognition over time is influenced by clinical characteristics during
      the early illness period. METHODS: Thirty-one EOS patients and 73 controls (age
      12-18) were assessed on clinical variables at baseline (PANSS, duration of
      untreated psychosis [DUP], hospitalizations, suicide attempts, and remission).
      Neuropsychological assessments with the MATRICS Consensus Cognitive Battery
      (MCCB) were conducted at baseline and after both 1 and 2 years, and composite
      scores of total performances were calculated. The analyses were performed with a
      linear mixed model. RESULTS: The present study found that global cognition
      followed a stable course over the first years of the disease in EOS, though at a
      significantly lower level in EOS compared with the controls. We did not detect a
      relationship between DUP, remission, positive/negative symptoms, and
      hospitalizations on one hand, and long-term cognition on the other hand, but
      PANSS-general and suicide attempt history at baseline were identified as risk
      factors of longitudinal cognitive function. CONCLUSIONS: Though at different
      levels, the EOS group and the controls had a similar cognitive course over 2
      years. Some baseline characteristics (psychotic symptoms, DUP, remission, and
      hospitalization) had no influence on cognition within the first 2 years of
      illness. In contrast, general symptoms and a history of suicide attempts at
      baseline were more potent risk factors of the cognitive course than the psychotic
      specific symptoms, and should, therefore, be subject to specific attention in the
      evaluation and treatment of patients with early-onset psychosis.

PMID- 29573346
TI  - Isolated Fallopian Tube Torsion: A Unique Ultrasound Identity or a Serial
      Copycat?
AB  - OBJECTIVES: To report the preoperative ultrasound (US) signs of isolated
      fallopian tube torsion in surgically verified cases and to estimate whether
      preoperative US detection of this condition can be improved. METHODS: The charts
      of 27 women with a surgical diagnosis of isolated fallopian tube torsion at a
      tertiary medical center from 2005 to 2016 were retrospectively reviewed. Data
      were collected from the electronic database of the US unit and compared with the
      surgical findings. RESULTS: Isolated fallopian tube torsion was correctly
      diagnosed by US before surgery in 8 of the 27 women (29.6%). In the remainder,
      the US signs were attributed to torsion of the ovary or the entire adnexa (n =
      13), or no torsion was suspected (n = 6). Fallopian tube edema was listed as a US
      finding in 7 patients, of whom 5 had a correct diagnosis of isolated fallopian
      tube torsion. The presence of a paraovarian cyst concomitant with normal
      appearing ovaries was assumed by US in 5 of the 8 cases that were accurately
      diagnosed as isolated fallopian tube torsion. The most misinterpreted US finding
      was an ovarian cyst (suspected in 10 patients and verified at surgery in 2).
      Absence of blood flow was described in 12 women, of whom 5 had an accurate
      diagnosis of isolated fallopian tube torsion. Six of the patients with a correct
      US diagnosis were adults (37.5% of total adults), and 2 were adolescents (18.2%
      of total adolescents). CONCLUSIONS: The US diagnosis of isolated fallopian tube
      torsion is challenging. A high index of suspicion is necessary to improve its
      detection, especially when there are possible US signs of torsion in the presence
      of a normal-appearing ovary.

PMID- 29573347
TI  - 5-Aza-7-deaza-2'-deoxyguanosine and 2'-Deoxycytidine Form Programmable Silver
      Mediated Base Pairs with Metal Ions in the Core of the DNA Double Helix.
AB  - 5-Aza-7-deaza-2'-deoxyguanosine (dZ) forms a silver-mediated base pair with dC.
      The metal ion pair represents a mimic of the H-bonded Watson-Crick dG-dC pair.
      The modified nucleoside displays a similar shape as the parent 2'-deoxyguanosine
      from which it can be constructed by transposition of nitrogen-7 to the bridgehead
      position-5. It lacks the major groove binding site as the positional change moves
      the dG- acceptor position from nitrogen-7 to nitrogen-1. As a shape mimic of dG,
      it fits nicely in the DNA double helix. The purine-pyrimidine dZ-dC hetero pair
      shows a relationship to the pyrimidine-pyrimidine dC-dC homo base pair. The dZ-dC
      pair forms a mismatch in the absence of silver ions and matches after addition of
      metal ions. Base-pair formation was verified on self-complementary 6-mer duplexes
      and 12-mer DNA with random composition by UV-dependent Tm measurements. Modified
      silver-mediated and hydrogen-bonded canonical base pairs can coexist. The dZ-Ag+ 
      dC base pair is slightly less stable than the dG-dC pair, shows sequence
      dependence, and consumes one or two silver ions. These properties make the dZ-Ag+
      -dC pair suitable for programmable incorporation of silver ions in DNA which
      cannot be achieved by canonical base pairs. If the silver ion content is higher
      than the total number of base pairs the duplexes turn into very stable structures
      in which all base pairs are considered to be in the silver-mediated pairing mode.

PMID- 29573348
TI  - Ephedrine-induced erythrodermia: Clinical diagnostic procedure and cross
      sensitivity.

PMID- 29573349
TI  - Influence of Filler Pore Structure and Polymer on the Performance of MOF-Based
      Mixed-Matrix Membranes for CO2 Capture.
AB  - To gain insight into the influence of metal-organic framework (MOF) fillers and
      polymers on membrane performance, eight different composites were studied by
      combining four MOFs and two polymers. MOF materials (NH2 -MIL-53(Al), MIL-69(Al),
      MIL-96(Al) and ZIF-94) with various chemical functionalities, topologies, and
      dimensionalities of porosity were employed as fillers, and two typical polymers
      with different permeability-selectivity properties (6FDA-DAM and Pebax) were
      selected as matrices. The best-performing MOF-polymer composites were prepared by
      loading 25 wt % of MIL-96(Al) as filler, which improved the permeability and
      selectivity of 6FDA-DAM to 32 and 10 %, while for Pebax they were enhanced to 25
      and 18 %, respectively. The observed differences in membrane performance in the
      separation of CO2 from N2 are explained on the basis of gas solubility,
      diffusivity properties, and compatibility between the filler and polymer phases.

PMID- 29573350
TI  - A microscale HPLC-UV method for the determination of latamoxef in plasma: An
      adapted method for therapeutic drug monitoring in neonates.
AB  - Latamoxef, a broad-spectrum anti-bacterial agent of the beta-lactam antibiotics,
      is used off-label in treatment of neonatal sepsis. Large inter-individual
      variability and uncertainty of treatment make therapeutic drug monitoring (TDM)
      useful to optimize antimicrobial therapy. The objective of this study was to
      develop and validate a simple, selective and reliable HPLC method for the
      determination of latamoxef in small volumes of plasma, which could be used in
      neonatal TDM. After a simple protein precipitation, analytes were separated with
      liquid chromatography and quantified by UV detection, with tinidazole as the
      internal standard. The calibration range was linear from 3.0 to 60.0 MUg/mL.
      Intra- and inter-day precisions were < 7.2%. The acceptance criteria of accuracy
      (between 85 and 115%, 120% for lower limit of quantification) were met in all
      cases. A plasma volume of 50 MUL was required to achieve the limit of
      quantification of 3.0 MUg/mL. The TDM results showed a large variability in
      trough concentrations. A large number of patients were underdosed, highlighting
      the unmet need for TDM to optimize latamoxef therapy in neonates.

PMID- 29573351
TI  - Client and therapist match on gender, age, and income: Does match within the
      therapeutic dyad predict early growth in the therapeutic alliance?
AB  - OBJECTIVE: Because of the importance of the therapeutic alliance across
      psychotherapeutic treatments, it is important to study variables that predict the
      development of a positive therapeutic alliance. This study investigates if
      different levels of gender, age, and income match between therapists and clients
      predict early development of the therapeutic alliance. METHOD: The sample
      consisted of 28 therapists and 547 adult clients receiving individual
      psychotherapy for depressive symptoms. There were no exclusion criteria and no
      control over treatment delivery. Session-to-session assessments of the
      therapeutic alliance were collected and a growth mixture modeling framework with
      a priori identified classes corresponding to different levels of therapist-client
      match was utilized to examine differential alliance growth trajectories. RESULTS:
      No differential effect of match on any level was found on initial ratings of the
      alliance. Across levels of attribute match, clients tend to rate the alliance
      positively. Regarding growth, a "youth effect" and an "affluence effect" was
      noted. Dyads where the therapist is younger than the client, and dyads where the
      therapist is from a higher income status than the client, show additional growth
      in the alliance beyond positive initial ratings. This is effect is not constant
      across sessions. CONCLUSIONS: Matching on gender, income, and age can be used for
      case assignment heuristic, in particular to produce additional growth in the
      alliance beyond initial positive ratings. Clinical and scientific consequences of
      the study are discussed.

PMID- 29573352
TI  - Anti-high mobility group box-1 monoclonal antibody treatment of brain edema
      induced by influenza infection and lipopolysaccharide.
AB  - Encephalopathy is a major cause of influenza-associated child death and severe
      neurological sequelae in Japan, highlighting the urgent need for new therapeutic
      strategies. In this study, we evaluated the effects of anti-high mobility group
      box-1 monoclonal antibody (alpha-HMGB1) treatment on brain edema induced by
      influenza A virus (IAV) and lipopolysaccharide in 4-week-old BALB/c female mice.
      The results showed that administration of 7.5 mg/kg alpha-HMGB1 1 h after IAV
      (A/Puerto Rico/8/34) inoculation significantly alleviated brain edema at 48 h
      after IAV inoculation, as confirmed by the suppression of Evans Blue dye leakage
      and matrix metallopeptidase-9 mRNA expression in the brain. Moreover, we also
      observed suppression of oxidative stress and different cytokines in IAV
      inoculated mice. The expression of plasminogen activator inhibitor-1 was also
      attenuated following treatment with alpha-HMGB1. Notably, alpha-HMGB1 treatment
      had no effect on virus propagation in the lung. In summary, anti-HMGB1 treatment
      may improve the prognosis in cases with influenza-associated encephalopathy by
      attenuating brain edema and reducing the inflammatory responses induced by HMGB1.

PMID- 29573353
TI  - Influence of white matter injury on gray matter reactive gliosis upon stab wound
      in the adult murine cerebral cortex.
AB  - Traumatic brain injury frequently affects the cerebral cortex, yet little is
      known about the differential effects that occur if only the gray matter (GM) is
      damaged or if the injury also involves the white matter (WM). To tackle this
      important question and directly compare similarities and differences in reactive
      gliosis, we performed stab wound injury affecting GM and WM (GM+) and one
      restricted to the GM (GM-) in the adult murine cerebral cortex. First, we
      examined glial reactivity in the regions affected (WM and GM) and determined the
      influence of WM injury on reactive gliosis in the GM comparing the same area in
      the two injury paradigms. In the GM+ injury microglia proliferation is increased
      in the WM compared with GM, while proliferating astrocytes are more abundant in
      the GM than in the WM. Interestingly, WM lesion exerted a strong influence on the
      proliferation of the GM glial cells that was most pronounced at early stages, 3
      days post lesion. While astrocyte proliferation was increased, NG2 glia
      proliferation was decreased in the GM+ compared with GM- lesion condition.
      Importantly, these differences were not observed when a lesion of the same size
      affected only the GM. Unbiased proteomic analyses further corroborate our
      findings in support of a profound difference in GM reactivity when WM is also
      injured and revealed MIF as a key regulator of NG2 glia proliferation.

PMID- 29573354
TI  - Validating screening tools for depression in Parkinson's disease.

PMID- 29573355
TI  - Association of plasma neopterin with risk of an inpatient hospital diagnosis of
      atrial fibrillation: results from two prospective cohort studies.
AB  - BACKGROUND: Link between inflammation and atrial fibrillation (AF) has been
      increasingly recognized. Neopterin, a biomarker of cellular immune activation,
      may be associated with incident AF. OBJECTIVE: To investigate the association
      between plasma neopterin levels and risk of an inpatient hospital diagnosis of
      AF, and to evaluate a joint association of neopterin and a nonspecific
      inflammatory marker C-reactive protein (CRP) in two prospective cohorts. METHODS:
      We performed a prospective analysis from a community-based cohort (the Hordaland
      Health Study (HUSK), n = 6891), and validated the findings in a cohort of
      patients with suspected stable angina pectoris (the Western Norway Coronary
      Angiography Cohort (WECAC), n = 2022). RESULTS: In both cohorts, higher plasma
      levels of neopterin were associated with an increased risk of incident AF after
      adjustment for age, sex, body mass index, current smoking, diabetes, hypertension
      and renal function. The multivariable-adjusted hazard ratio (HR) (95% CI) per one
      SD increment of log-transformed neopterin was 1.20 (1.10-1.32) in HUSK and 1.26
      (1.09-1.44) in WECAC. Additional adjustment for CRP did not materially affect the
      risk association for neopterin. The highest risk of AF was found among
      individuals with both neopterin and CRP levels above the median (HR: 1.54; 95%
      CI: 1.16-2.05 in HUSK and HR: 1.67; 95% CI: 1.11-2.52 in WECAC). CONCLUSIONS: Our
      findings indicate an association of plasma neopterin with risk of an inpatient
      hospital diagnosis of AF, which remains after adjustment for traditional risk
      factors as well as for CRP. This study highlights a role of cellular immune
      activation, in addition to inflammation, in AF pathogenesis.

PMID- 29573357
TI  - Rotavirus surveillance in Pakistan during 2015-2016 reveals high prevalence of
      G12P[6].
AB  - The G12 rotavirus genotype has emerged globally since their first detection in
      1987 from the Philippines; however it remains a rare cause of gastroenteritis in
      Pakistan. Rotavirus surveillance conducted during 2015-2016, assessed 3446
      children <5 years hospitalized for gastroenteritis and found 802 (23.2%) positive
      on ELISA. Genotyping of a subset of positive samples (n = 319) revealed G12P[6]
      (11.28%) as the third most common G/P combination following G3P[8] (28.5%) and
      G1P[8] (12.5%); G2P[4] (10.65%) and G3P[6] (8.15%) were other frequently detected
      strains. Phylogenetic analysis of G12 strains from Pakistan revealed high genetic
      similarity to G12 strains from Italy, Thailand, Korea, and Great Britain as well
      as local strains within G12 lineage III. In conclusion, G12P[6] was a major
      contributor of RVA gastroenteritis in Pakistani children. Robust surveillance
      after the introduction of rotavirus vaccines will help determine the evolution of
      G12 and other circulating genotypes in the country.

PMID- 29573356
TI  - Optimization of selective inversion recovery magnetization transfer imaging for
      macromolecular content mapping in the human brain.
AB  - PURPOSE: To optimize a selective inversion recovery (SIR) sequence for
      macromolecular content mapping in the human brain at 3.0T. THEORY AND METHODS:
      SIR is a quantitative method for measuring magnetization transfer (qMT) that uses
      a low-power, on-resonance inversion pulse. This results in a biexponential
      recovery of free water signal that can be sampled at various inversion/predelay
      times (tI/ tD ) to estimate a subset of qMT parameters, including the
      macromolecular-to-free pool-size-ratio (PSR), the R1 of free water (R1f ), and
      the rate of MT exchange (kmf ). The adoption of SIR has been limited by long
      acquisition times (~4 min/slice). Here, we use Cramer-Rao lower bound theory and
      data reduction strategies to select optimal tI /tD combinations to reduce imaging
      times. The schemes were experimentally validated in phantoms, and tested in
      healthy volunteers (N = 4) and a multiple sclerosis patient. RESULTS: Two optimal
      sampling schemes were determined: (i) a 5-point scheme (kmf estimated) and (ii) a
      4-point scheme (kmf assumed). In phantoms, the 5/4-point schemes yielded
      parameter estimates with similar SNRs as our previous 16-point scheme, but with
      4.1/6.1-fold shorter scan times. Pair-wise comparisons between schemes did not
      detect significant differences for any scheme/parameter. In humans, parameter
      values were consistent with published values, and similar levels of precision
      were obtained from all schemes. Furthermore, fixing kmf reduced the sensitivity
      of PSR to partial-volume averaging, yielding more consistent estimates throughout
      the brain. CONCLUSIONS: qMT parameters can be robustly estimated in <=1 min/slice
      (without independent measures of DeltaB0 , B1+, and T1 ) when optimized tI -tD
      combinations are selected.

PMID- 29573359
TI  - Mental health problems among clinical psychologists: Stigma and its impact on
      disclosure and help-seeking.
AB  - OBJECTIVE(S): To assess the prevalence of personal experiences of mental health
      problems among clinical psychologists, external, perceived, and self-stigma among
      them, and stigma-related concerns relating to disclosure and help-seeking.
      METHOD: Responses were collected from 678 UK-based clinical psychologists through
      an anonymous web survey consisting of the Social Distance Scale, Stig-9, Military
      Stigma Scale, Secrecy Scale, Attitudes towards Seeking Professional Psychological
      Help Scale-Short Form, alongside personal experience and socio-demographic
      questions. RESULTS: Two-thirds of participants had experienced mental health
      problems themselves. Perceived mental health stigma was higher than external and
      self-stigma. Participants were more likely to have disclosed in their social than
      work circles. Concerns about negative consequences for self and career, and shame
      prevented some from disclosing and help-seeking. CONCLUSIONS: Personal
      experiences of mental health problems among clinical psychologists may be fairly
      common. Stigma, concerns about negative consequences of disclosure and shame as
      barriers to disclosure and help-seeking merit further consideration.

PMID- 29573358
TI  - Growing Azolla to produce sustainable protein feed: the effect of differing
      species and CO2 concentrations on biomass productivity and chemical composition.
AB  - BACKGROUND: Since available arable land is limited and nitrogen fertilizers
      pollute the environment, cropping systems ought to be developed that do not rely
      on them. Here we investigate the rapidly growing, N2 -fixing Azolla/Nostoc
      symbiosis for its potential productivity and chemical composition to determine
      its potential as protein feed. RESULTS: In a small production system, cultures of
      Azolla pinnata and Azolla filiculoides were continuously harvested for over 100
      days, yielding an average productivity of 90.0-97.2 kg dry weight (DW) ha-1  d-1
      . Under ambient CO2 levels, N2 fixation by the fern's cyanobacterial symbionts
      accounted for all nitrogen in the biomass. Proteins made up 176-208 g kg-1 DW
      (4.9 * total nitrogen), depending on species and CO2 treatment, and contained
      more essential amino acids than protein from soybean. Elevated atmospheric CO2
      concentrations (800 ppm) significantly boosted biomass production by 36-47%,
      without decreasing protein content. Choice of species and CO2 concentrations
      further affected the biomass content of lipids (79-100 g kg-1 DW) and
      (poly)phenols (21-69 g kg-1 DW). CONCLUSIONS: By continuous harvesting, high
      protein yields can be obtained from Azolla cultures, without the need for
      nitrogen fertilization. High levels of (poly)phenols likely contribute to
      limitations in the inclusion rate of Azolla in animal diets and need further
      investigation. (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- 29573360
TI  - Potential amelioration of nicotine-induced toxicity by nanocurcumin.
AB  - Clinical Research Curcumin, a nontoxic bioactive agent of turmeric significantly
      reduces nicotine-induced toxicity both at cellular and genetic levels. The
      clinical implication of native curcumin is hindered in the target cells due to
      its low aqueous solubility, poor bioavailability and poor pharmacokinetics. The
      problem was tried to overcome by preparing nanocurcumin with a view to improve
      its aqueous solubility and better therapeutic efficacy against nicotine-induced
      toxicity. The prepared nanocurcumin was characterized by Ultraviolet-visible
      spectroscopy; Field emission scanning electron microscopy (FE-SEM); X-ray
      diffraction (XRD); and Fourier transform infrared spectroscopy (FTIR). Female
      albino rats of Wistar strain were daily exposed to effective dose of nicotine
      (2.5 mg/kg, injected subcutaneously) and supplemented with effective dose of
      curcumin (80 mg/kg body weight orally) or nanocurcumin (4 mg/kg body weight
      orally) for 21 days. The preventive efficacies of curcumin and nanocurcumin were
      evaluated against the changes in liver function enzymes, kidney function
      parameters, lipid profiles, lipid-peroxidation, anti-oxidant status, and tissues
      damages etc. Results revealed that nanocurcumin more effectively ameliorated the
      nicotine-induced toxicities at much lower concentration due to its higher aqueous
      solubility and more bioavailability. The nanocurcumin can be used as a potential
      therapeutic agent for better efficacy against nicotine-induced toxicities than
      native curcumin.

PMID- 29573361
TI  - RoMo: An efficient strategy for functional mosaic analysis via stochastic Cre
      recombination and gene targeting in the ROSA26 locus.
AB  - Functional mosaic analysis allows for the direct comparison of mutant cells with
      differentially marked control cells in the same organism. While this offers a
      powerful approach for elucidating the role of specific genes or signalling
      pathways in cell populations of interest, genetic strategies for generating
      functional mosaicism remain challenging. We describe a novel and streamlined
      approach for functional mosaic analysis, which combines stochastic Cre/lox
      recombination with gene targeting in the ROSA26 locus. With the RoMo strategy a
      cell population of interest is randomly split into a cyan fluorescent and red
      fluorescent subset, of which the latter overexpresses a chosen transgene. To
      integrate this approach into high-throughput gene targeting initiatives, we
      developed a procedure that utilizes Gateway cloning for the generation of new
      targeting vectors. RoMo can be used for gain-of-function experiments or for
      altering signaling pathways in a mosaic fashion. To demonstrate this, we
      developed RoMo-dnGs mice, in which Cre-recombined red fluorescent cells co
      express a dominant-negative Gs protein. RoMo-dnGs mice allowed us to inhibit G
      protein-coupled receptor activation in a fraction of cells, which could then be
      directly compared to differentially marked control cells in the same animal. We
      demonstrate how RoMo-dnGs mice can be used to obtain mosaicism in the brain and
      in peripheral organs for various cell types. RoMo offers an efficient new
      approach for functional mosaic analysis that extends the current toolbox and may
      reveal important new insights into in vivo gene function.

PMID- 29573362
TI  - Management of myringitis: Current concepts and review.
AB  - OBJECTIVES: This study reviews the proposed mechanisms underlying the development
      of myringitis and suggests optimal guidelines for the successful treatment and
      prevention of recurrence through a literature review. REVIEW METHODS: Studies
      reporting the treatment outcomes of myringitis were systematically reviewed by
      searching the MEDLINE, PubMed, and Embase databases for studies published from
      2000 to 2017. The search for myringitis yielded 57 results, and 31 were found to
      be relevant. Thirteen articles related to bullous myringitis associated with
      acute otitis media were excluded; the remaining 18 were included in this study.
      The studies were reviewed with attention to clinical characteristics, treatment
      options, and results after treatment. RESULTS: Among 18 publications, 10
      suggested therapeutic options for myringitis: 1) five studies suggested
      management using topical agents, 2) three studies suggested laser-assisted
      treatment, and 3) two studies suggested surgical treatment. Treatments using
      topical agents or a laser showed highly variable resolution rates (63.6%-100% and
      20%-85.7%, respectively). Two studies introducing surgical therapy reported good
      treatment outcomes (95.8%-100%). Five articles discussed the characteristics or
      diagnosis of myringitis; however, there was a lack of evidence for the related
      mechanism. CONCLUSIONS: No well-designed randomized studies have assessed optimal
      treatments. Although surgery showed better treatment results than topical agents
      and laser-assisted treatment, the wide range of resolution rates indicates that
      proper patient selection is needed. Further studies are needed to improve the
      current understanding and management of myringitis. Laryngoscope, 128:2157-2162,
      2018.

PMID- 29573364
TI  - Multiple gateways.

PMID- 29573363
TI  - Ruptured intracranial aneurysm in an adolescent with infective endocarditis.

PMID- 29573365
TI  - Fundamental drivers for endolithic microbial community assemblies in the
      hyperarid Atacama Desert.
AB  - In hyperarid deserts, endolithic microbial communities colonize the rocks'
      interior as a survival strategy. Yet, the composition of these communities and
      the drivers promoting their assembly are still poorly understood. We analysed the
      diversity and community composition of endoliths from four different lithic
      substrates - calcite, gypsum, ignimbrite and granite - collected in the hyperarid
      zone of the Atacama Desert, Chile. By combining microscopy, mineralogy,
      spectroscopy and high throughput sequencing, we found these communities to be
      highly specific to their lithic substrate, although they were all dominated by
      the same four main phyla, Cyanobacteria, Actinobacteria, Chloroflexi and
      Proteobacteria. Our finding indicates a fine scale diversification of the
      microbial reservoir driven by substrate properties. The data suggest that the
      overall rock chemistry and the light transmission properties of the substrates
      are not essential drivers of community structure and composition. Instead, we
      propose that the architecture of the rock, i.e., the space available for
      colonization and its physical structure, linked to water retention capabilities,
      is ultimately the driver of community diversity and composition at the dry limit
      of life.

PMID- 29573366
TI  - Inhibition in the face of emotion: Characterization of the spatial-temporal
      dynamics that facilitate automatic emotion regulation.
AB  - Emotion regulation mediates socio-cognitive functions and is essential for
      interactions with others. The capacity to automatically inhibit responses to
      emotional stimuli is an important aspect of emotion regulation; the underlying
      neural mechanisms of this ability have been rarely investigated. Forty adults
      completed a Go/No-go task during magnetoencephalographic (MEG) recordings, where
      they responded rapidly to either a blue or purple frame which contained angry or
      happy faces. Subjects responded to the target color in an inhibition (75% Go
      trials) and a vigilance condition (25% Go trials). As expected, inhibition
      processes showed early, sustained activation (200-450 ms) in the right inferior
      frontal gyrus (IFG). Emotion-related inhibition processes showed greater activity
      with angry faces bilaterally in the orbital-frontal gyri (OFG) starting at 225 ms
      and temporal poles from 250 ms, with right hemisphere dominance. The presence of
      happy faces elicited earlier activity in the right OFG. This study demonstrates
      that the timing of inhibition processes varies with the emotional context and
      that there is much greater activation in the presence of angry faces. It
      underscores the importance of the right IFG for inhibition processes, but the OFG
      in automatic emotion regulation.

PMID- 29573367
TI  - Proteome and acylome analyses of the functional interaction network between the
      carbazole-degradative plasmid pCAR1 and host Pseudomonas putida KT2440.
AB  - Understanding the interplay between a plasmid and its host system is a bottleneck
      towards prediction of the fate of plasmid-harbouring strains in the natural
      environments. Here, we studied the impact of the conjugative plasmid pCAR1,
      involved in carbazole degradation, on the proteome of Pseudomonas putida KT2440
      using SILAC method. Furthermore, we investigated two acyl lysine modifications
      (acetylation and succinylation) that respond to the metabolic status of the cell
      and are implicated in regulation of various cellular processes. The total
      proteome analysis revealed that the abundance of key proteins involved in
      metabolism, signal transduction and motility was affected by pCAR1 carriage. In
      total, we identified 1359 unique acetylation sites on 637 proteins and 567 unique
      succinylation sites on 259 proteins. Changes in the acylation status of proteins
      involved in metabolism and translation by pCAR1 carriage were detected.
      Remarkably, acylation was identified on proteins involved in important plasmid
      functions, including partitioning and carbazole degradation, and on nucleoid
      associated proteins that play a key role in the functional interaction with the
      chromosome. This study provides a novel insight on the functional consequences of
      plasmid carriage and improves our understanding of the plasmid-host cross-talk.

PMID- 29573368
TI  - Supramolecular Organization in Confined Nanospaces.
AB  - Empty spaces are abhorred by nature, which immediately rushes in to fill the
      void. Humans have learnt pretty well how to make ordered empty nanocontainers,
      and to get useful products out of them. When such an order is imparted to
      molecules, new properties may appear, often yielding advanced applications. This
      review illustrates how the organized void space inherently present in various
      materials: zeolites, clathrates, mesoporous silica/organosilica, and metal
      organic frameworks (MOF), for example, can be exploited to create confined,
      organized, and self-assembled supramolecular structures of low dimensionality.
      Features of the confining matrices relevant to organization are presented with
      special focus on molecular-level aspects. Selected examples of confined
      supramolecular assemblies - from small molecules to quantum dots or luminescent
      species - are aimed to show the complexity and potential of this approach.
      Natural confinement (minerals) and hyperconfinement (high pressure) provide
      further opportunities to understand and master the atomistic-level interactions
      governing supramolecular organization under nanospace restrictions.

PMID- 29573369
TI  - Effect of hydraulic retention time on microbial community structure in wastewater
      treatment electro-bioreactors.
AB  - The impact of hydraulic retention time (HRT) on the performance and microbial
      community structure of control and electro-bioreactors was investigated. Control
      bioreactors and electro-bioreactors were operated at HRT ranging between 6 and 75
      hr. The total bacterial counts in addition to the removal efficiency of NH4+ -N,
      sCOD, and PO43- -P was assessed in all the reactors tested. In addition, Illumina
      sequencing was performed to determine the microbial communities that developed in
      these reactors under each HRT condition. Phylogenetic analysis showed that
      Proteobacteria and Bacteroidetes were the dominant phyla in those reactors. In
      addition, Nitrospira sp. and Pseudomonas sp. were found to be present in electro
      bioreactors with higher relative abundance than in control bioreactors. The
      results presented here are the first to determine what different microbial
      communities in wastewater electro-bioreactors due to the application of an
      electric current under different HRTs.

PMID- 29573370
TI  - Nutrition-sensitive agricultural interventions and gender dynamics: A qualitative
      study in Nepal.
AB  - Undernutrition and low women's status persist as major development obstacles in
      South Asia and specifically, Nepal. Multi-sectoral approaches, including
      nutrition-sensitive agriculture, are potential avenues for further reductions in
      undernutrition. Although evidence is growing, many questions remain regarding how
      gender mediates the translation of agricultural production activities into
      nutritional benefit. In this study, we examined how gender influences the pathway
      from agricultural production to improved income and control of income, with a
      focus on five domains of empowerment: decision-making power, freedom of mobility,
      social support, workload and time, and self-efficacy. For this, we conducted a
      qualitative retrospective assessment (N = 10 FGDs) among 73 beneficiary women of
      a nutrition-sensitive agriculture programme implemented from 2008 to 2012 in two
      districts of Nepal-Baitadi and Kailali. We found that women reported increased
      decision-making power, new knowledge and skills, increased recognition by their
      family members of their new knowledge and contributions, and self-efficacy as
      farmers and sellers, whereas workload and time were the most consistent
      constraints noted. We also found that each empowerment domain operated
      differently at different stages of the pathway, sometimes representing barriers
      and at other times, opportunities and that the interconnectedness of the domains
      made them difficult to disentangle in practice. Finally, there were major
      contextual differences for some domains (e.g., freedom of mobility) between the
      two districts. Future policies and programmes need to include in-depth formative
      research to ensure that interventions address context-specific gender and social
      norms to maximise programmatic opportunities to achieve desired results.

PMID- 29573371
TI  - Effect of applied magnetic fields on motility and magnetotaxis in the uncultured
      magnetotactic multicellular prokaryote 'Candidatus Magnetoglobus
      multicellularis'.
AB  - Magnetotactic bacteria are found in the chemocline of aquatic environments
      worldwide. They produce nanoparticles of magnetic minerals arranged in chains in
      the cytoplasm, which enable these microorganisms to align to magnetic fields
      while swimming propelled by flagella. Magnetotactic bacteria are diverse
      phylogenetically and morphologically, including cocci, rods, vibria, spirilla and
      also multicellular forms, known as magnetotactic multicellular prokaryotes
      (MMPs). We used video-microscopy to study the motility of the uncultured MMP
      'Candidatus Magnetoglobus multicellularis' under applied magnetic fields ranging
      from 0.9 to 32 Oersted (Oe). The bidimensional projections of the tridimensional
      trajectories where interpreted as plane projections of cylindrical helices and
      fitted as sinusoidal curves. The results showed that 'Ca. M. multicellularis' do
      not orient efficiently to low magnetic fields, reaching an efficiency of about
      0.65 at 0.9-1.5 Oe, which are four to six times the local magnetic field. Good
      efficiency (0.95) is accomplished for magnetic fields >=10 Oe. For comparison,
      unicellular magnetotactic microorganisms reach such efficiency at the local
      magnetic field. Considering that the magnetic moment of 'Ca. M. multicellularis'
      is sufficient for efficient alignment at the Earth's magnetic field, we suggest
      that misalignments are due to flagella movements, which could be driven by photo
      , chemo- and/or other types of taxis.

PMID- 29573372
TI  - Mixotrophic metabolism by natural communities of unicellular cyanobacteria in the
      western tropical South Pacific Ocean.
AB  - Cyanobacteria are major contributors to ocean biogeochemical cycling. However,
      mixotrophic metabolism and the relative importance of inorganic and organic
      carbon assimilation within the most abundant cyanobacteria are still poorly
      understood. We explore the ability of Prochlorococcus and Synechococcus to
      assimilate organic molecules with variable C:N:P composition and its modulation
      by light availability and photosynthetic impairment. We used a combination of
      radiolabelled molecules incubations with flow cytometry cell sorting to separate
      picoplankton groups from the western tropical South Pacific Ocean.
      Prochlorococcus and Synechococcus assimilated glucose, leucine and ATP at all
      stations, but cell-specific assimilation rates of N and P containing molecules
      were significantly higher than glucose. Incubations in the dark or with an
      inhibitor of photosystem II resulted in reduced assimilation rates. Light
      enhanced cell-specific glucose uptake was generally higher for cyanobacteria
      (~50%) than for the low nucleic acid fraction of bacterioplankton (LNA, ~35%).
      Our results confirm previous findings, based mainly on cultures and genomic
      potentials, showing that Prochlorococcus and Synechococcus have a flexible
      mixotrophic metabolism, but demonstrate that natural populations remain primarily
      photoautotrophs. Our findings indicate that mixotrophy by marine cyanobacteria is
      more likely to be an adaptation to low inorganic nutrient availability rather
      than a facultative pathway for carbon acquisition.

PMID- 29573374
TI  - Silencing Arabidopsis CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-LIKE 4 induces
      cytokinin-oversensitive de novo shoot organogenesis.
AB  - De novo shoot organogenesis (DNSO) is a post-embryonic development programme that
      has been widely exploited by plant biotechnology. DNSO is a hormonally regulated
      process in which auxin and cytokinin (CK) coordinate suites of genes encoding
      transcription factors, general transcription factors, and RNA metabolism
      machinery. Here we report that silencing Arabidopsis thaliana carboxyl-terminal
      domain (CTD) phosphatase-like 4 (CPL4RNAi ) resulted in increased phosphorylation
      levels of RNA polymerase II (pol II) CTD and altered lateral root development and
      DNSO efficiency of the host plants. Under standard growth conditions, CPL4RNAi
      lines produced no or few lateral roots. When induced by high concentrations of
      auxin, CPL4RNAi lines failed to produce focused auxin maxima at the meristem of
      lateral root primordia, and produced fasciated lateral roots. In contrast, root
      explants of CPL4RNAi lines were highly competent for DNSO. Efficient DNSO of
      CPL4RNAi lines was observed even under 10 times less the CK required for the wild
      type explants. Transcriptome analysis showed that CPL4RNAi , but not wild-type
      explants, expressed high levels of shoot meristem-related genes even during
      priming on medium with a high auxin/CK ratio, and during subsequent shoot
      induction with a lower auxin/CK ratio. Conversely, CPL4RNAi enhanced the
      inhibitory phenotype of the shoot redifferentiation defective2-1 mutation, which
      affected snRNA biogenesis and formation of the auxin gradient. These results
      indicated that CPL4 functions in multiple regulatory pathways that positively and
      negatively affect DNSO.

PMID- 29573373
TI  - The role of conserved charged residues in the bidirectional rotation of the
      bacterial flagellar motor.
AB  - Many bacteria rotate their flagella both counterclockwise (CCW) and clockwise
      (CW) to achieve swimming toward attractants or away from repellents. Highly
      conserved charged residues are important for that motility, which suggests that
      electrostatic interactions are crucial for the rotor-stator function. It remains
      unclear if those residues contribute equally to rotation in the CCW and CW
      directions. To address this uncertainty, in this study, we expressed chimeric
      rotors and stators from Vibrio alginolyticus and Escherichia coli in E. coli, and
      measured the rotational speed of each motor in both directions using a tethered
      cell assay. In wild-type cells, the rotational speeds in both directions were
      equal, as demonstrated previously. Some charge-neutralizing residue replacements
      in the stator decreased the rotational speed in both directions to the same
      extent. However, mutations in two charged residues in the rotor decreased the
      rotational speed only in the CCW direction. Subsequent analysis and previous
      results suggest that these amino acid residues are involved in supporting the
      conformation of the rotor, which is important for proper torque generation in the
      CCW direction.

PMID- 29573375
TI  - Anaesthetic efficacy of 4% articaine and 2% lidocaine for extraction and
      pulpotomy of mandibular primary molars: an equivalence parallel prospective
      randomized controlled trial.
AB  - AIM: To compare the anaesthetic efficacy for pain and behaviour during treatment
      with mandibular infiltration using 4% articaine (BI) with inferior dental nerve
      clock (IDNB) using 2% lidocaine for extraction or pulp therapy in mandibular
      primary molars. DESIGN: This was equivalence parallel prospective RCT. A total of
      98 children aged 5-9 years old were randomly assigned into two groups: BI
      supplemented by buccal intrapapillary infiltration with 4% articaine; IDNB with
      2% lidocaine supplemented with long buccal infiltration. Behaviour during the
      injection and treatment procedures was assessed using Wong-Baker Facial Rating
      Scale (W-BFRS), Visual Analogue Scale (VAS), and Frankl Behaviour Rating Scale
      (FBRS). RESULTS: During the injection phase, the absolute differences in success
      rates between the two techniques were 0.06 (95% CI: -0.11 to 0.23) for VAS and 
      0.08 (95% CI: -0.19 to 0.03) for the behaviour of the child (FBRS). FBRS results
      showed the equivalence of the two, whereas the VAS results showed nonequivalence
      with the 95% confidence intervals slightly exceeding the equivalence margin (+/
      0.20). W-BFRS success rates were 63.3% for both. During the treatment, VAS
      results showed similar success rates, demonstrating equivalence between the two
      as did the results for FBRS. CONCLUSION: The results suggested equivalence in
      success rates for both anaesthetic techniques during treatment.

PMID- 29573376
TI  - Chicken or egg? Outcomes of experimental manipulations of maternally transmitted
      hormones depend on administration method - a meta-analysis.
AB  - Steroid hormones are important mediators of prenatal maternal effects in animals.
      Despite a growing number of studies involving experimental manipulation of these
      hormones, little is known about the impact of methodological differences among
      experiments on the final results expressed as offspring traits. Using a meta
      analytical approach and a representative sample of experimental studies performed
      on birds, we tested the effect of two types of direct hormonal manipulations:
      manipulation of females (either by implantation of hormone pellets or injection
      of hormonal solutions) and manipulation of eggs by injection. In both types of
      manipulation we looked at the effects of two groups of hormones: corticosterone
      and androgens in the form of testosterone and androstenedione. We found that the
      average effect on offspring traits differed between the manipulation types, with
      a well-supported positive effect of egg manipulation and lack of a significant
      effect of maternal manipulation. The observed average positive effect for egg
      manipulation was driven mainly by androgen manipulations, while corticosterone
      manipulations exerted no overall effect, regardless of manipulation type.
      Detailed analyses revealed effects of varying size and direction depending on the
      specific offspring traits; e.g., egg manipulation positively affected physiology
      and behaviour (androgens), and negatively affected future reproduction
      (corticosterone). Effect size was negatively related to the dose of androgen
      injected into the eggs, but unrelated to timing of manipulation, offspring
      developmental stage at the time of measuring their traits, solvent type, the site
      of egg injection and maternal hormone delivery method. Despite the generally
      acknowledged importance of maternal hormones for offspring development in birds,
      the overall effect of their experimental elevation is rather weak, significantly
      heterogeneous and dependent on the hormone and type of manipulation. We conclude
      by providing general recommendations as to how hormonal manipulations should be
      performed in order to standardize their impact and the results achieved. We also
      emphasize the need for research on free-living birds with a focus on fitness
      related and other long-term effects of maternal hormones.

PMID- 29573377
TI  - The two major glucokinase isoforms show conserved functionality in beta-cells
      despite different subcellular distribution.
AB  - Glucokinase (GCK) is crucial to regulating glucose metabolism in the liver and in
      pancreatic beta-cells. There are two major GCK isoforms, hepatic and pancreatic
      GCKs, which differ only in exon 1. However, the functional differences between
      the two GCK isoforms remain poorly understood. Here, we used a beta-cell-targeted
      gene transfer vector to determine the impact of isoform-specific GCK
      overexpression on beta-cells in vitro and in vivo. We showed that pancreatic GCK
      had a nuclear localization signal unique to the pancreatic isoform, facilitating
      its nuclear distribution in beta-cells. Despite the difference in subcellular
      distribution, overexpression of GCK isoforms similarly enhanced glucose uptake
      and beta-cell proliferation in vitro. Overexpression of hepatic or pancreatic GCK
      also similarly enhanced beta-cell proliferation in normal diet mice without
      affecting fasting glucose and intraperitoneal glucose tolerance tests (IPGTT).
      Our further study on human GCK sequences identified disproportional GCK amino
      acid variants in exon 1, while mutations linked to maturity onset diabetes of the
      young type 2 (MODY2) were disproportionally found in exons 2 through 10. Our
      results therefore indicate functional conservation between the two major GCK
      isoforms despite their distinct subcellular distribution.

PMID- 29573378
TI  - Why do herpes simplex encephalitis and semantic dementia show a different pattern
      of semantic impairment in spite of their main common involvement within the
      anterior temporal lobes?
AB  - A very challenging problem in the domain of the cognitive neurosciences is to
      explain why herpes simplex encephalitis and semantic dementia show, respectively,
      a category-specific semantic disorder for biological entities and an across
      categories semantic disruption, despite highly overlapping areas of anterior
      temporal lobe damage. The aim of the present review consisted in trying to make a
      separate survey of anatomo-clinical investigations (single-case studies and group
      studies) and of activation studies, in order to analyse the factors that could
      explain these different patterns of semantic disruption. Factors taken into
      account in this review were laterality of lesions, disease aetiology, kind of
      brain pathology and locus of damage within the temporal lobes. Locus of damage
      within the temporal lobes and kind of brain pathology seemed to play the most
      important role, because in patients with herpes simplex encephalitis and category
      specific semantic disorder for biological entities the lesions prevailed in the
      anteromedial temporal lobes. Furthermore, the neuropathology concerned both the
      anterior temporal cortices and the white matter pathways connecting these areas
      with the posterior visual areas, whereas in semantic dementia the inferior
      longitudinal fasciculus involvement was restricted to the rostral temporal lobe
      and did not extend into the cortically uninvolved occipital lobe.

PMID- 29573379
TI  - Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in
      major depressive disorder and schizophrenia?
AB  - Abnormalities in reward processing are crucial symptoms of major depressive
      disorder (MDD) and schizophrenia (SCH). Recent neuroscientific findings regarding
      MDD have led to conclusions about two different symptoms related to reward
      processing: motivational and consummatory anhedonia, corresponding, respectively,
      to impaired motivation to obtain rewards ('wanting'), and diminished satisfaction
      from consuming them ('liking'). One can ask: which of these is common for MDD and
      SCH. In our review of the latest neuroscientific studies, we show that MDD and
      SCH do not share consummatory anhedonia, as SCH patients usually have unaltered
      liking. Therefore, we investigated whether motivational anhedonia is the common
      symptom across MDD and SCH. With regard to the similarities and differences
      between the neural mechanisms of MDD and SCH, here we expand the current
      knowledge of motivation deficits and present the common underlying mechanism of
      motivational anhedonia - the dopamine dysregulation hypothesis - stating that any
      prolonged dysregulation in tonic dopamine signaling that exceeds the given
      equilibrium can lead to striatal dysfunction and motivational anhedonia. The
      implications for further research and treatment of MDD and SCH are also
      discussed.

PMID- 29573380
TI  - PFGE: a tool for examination of heterogeneity between the bacterial spot-causing
      xanthomonads of tomato plants in Bulgaria.
AB  - Pulsed-field gel electrophoresis (PFGE) is a highly discriminative molecular
      typing method that is used for epidemiological studies and investigation of
      outbreaks caused by different pathogens, including phytopathogenic Xanthomonas
      species. Bacterial spot (BS) is the most common and one of the most destructive
      diseases of tomato and pepper plants in Bulgaria. Several Xanthomonas species are
      known to cause BS, but the global distribution and genetic diversity of these
      species are not well understood. A collection of 100 BS-causing strains, isolated
      during the period of 1985-2012 from different tomato cultivars and weeds
      associated with tomato production areas from 11 geographic regions in Bulgaria,
      were screened for genetic diversity by genomic DNA restriction with rare-cutting
      endonucleases (XbaI and SpeI) subsequently resolved by PFGE. Two haplotypes for
      Xanthomonas vesicatoria and one haplotype for Xanthomonas gardneri strains were
      found.

PMID- 29573381
TI  - Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in
      cultured human lymphocytes.
AB  - The present study aims at assessing the efficacies of olivetoric acid (OA) and
      physodic acid (PA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae)
      in human lymphocytes (HLs) in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to
      establish cytotoxicity in HLs. Besides, oxidative stress and genotoxicity were
      monitored by estimating the changes of total oxidative stress (TOS) and 8-hydroxy
      2'-deoxyguanosine (8-OH-dG) levels, respectively, in HLs. At the same time, OA-
      and PA-induced total antioxidant capacity (TAC) levels in HLs were determined.
      Although especially low concentrations of OA (IC50=109.94 mg/L) and PA
      (IC50=665.49 mg/L) did not show cytotoxic effect at high levels in HLs, it was
      revealed that cytotoxicity was significantly (p<0.05) associated with oxidative
      stress and genotoxicity via correlation analysis. While TOS level in HLs did not
      statistically (p>0.05) increase in the presence of all treatments (0.5-100 mg/L)
      of PA, TAC level was increased by PA applications in certain concentrations (0.5
      10 mg/L). Overall, the obtained data indicate that OA and especially PA as lichen
      compounds that do not cause oxidative stress can be a new resource of
      therapeutics as recognized in the present study with their high antioxidant
      features.

PMID- 29573383
TI  - ?

PMID- 29573382
TI  - Human Adipose-Derived and Amniotic Fluid-Derived Stem Cells: A Preliminary In
      Vitro Study Comparing Myogenic Differentiation Capability.
AB  - BACKGROUND Around the world, disabilities due to musculoskeletal disorders have
      increased and are a major health problem worldwide. In recent years, stem cells
      have been considered to be powerful tools for musculoskeletal tissue engineering.
      Human adipose-derived stem cells (hADSCs) and amniotic fluid-derived stem cells
      (hAFSCs) undergo typical differentiation process into cells of mesodermal origin
      and can be used to treat muscular system diseases. The aim of the present study
      was to compare the biological characteristic of stem cells isolated from
      different human tissues (adipose tissue and amniotic fluid) with respect to
      myogenic capacity and skeletal and smooth muscle differentiation under the same
      conditions. MATERIAL AND METHODS hAFSCs and hADSCs were isolated during standard
      medical procedures and widely characterized by specific markers expression and
      differentiation potential. Both cell types were induced toward smooth and
      striated muscles differentiation, which was assessed with the use of molecular
      techniques. RESULTS For phenotypic characterization, both stem cell types were
      assessed for the expression of OCT-4, SOX2, CD34, CD44, CD45, and CD90. Muscle
      specific markers appeared in both stem cell types, but the proportion of positive
      cells showed differences depending on the experimental conditions used and the
      source from which the stem cells were isolated. CONCLUSIONS In this study, we
      demonstrated that hADSCs and hAFSCs have different capability of differentiation
      toward both muscle types. However, hADSCs seem to be a better source for myogenic
      protocols and can promote skeletal and smooth muscle regeneration through either
      direct muscle differentiation or by paracrine mechanism.

PMID- 29573384
TI  - [Employment opportunities and job satisfaction in the field of Public Health: a
      survey among recent graduates of the Hygiene and Preventive Medicine residency in
      Italy].
AB  - We conducted an on-line survey among 255 specialists in Hygiene and Preventive
      Medicine in Italy who completed their training between October 2014 and July
      2016, to assess their training experience, employment opportunities and current
      job satisfaction. Response rate was 49%. Mean age was 35 years. A high employment
      rate within two years from obtaining specialist qualification was reported by the
      125 specialists who completed the questionnaire (76% are currently employed). The
      three main work settings of the participating specialists are hospital health
      directions (37%), universities (19%) and local Prevention Departments (16%). Two
      thirds (66%) have temporary positions and only 6% permanent positions. Job, pay,
      and training satisfaction are often below expectations with geographical
      differences that would need to be further investigated.

PMID- 29573385
TI  - [Hygienic suitability of food and food-contact surfaces in a hospital canteen:
      the experience of a University Hospital in Italy].
AB  - The Authors present the results of a study performed during a time-period of two
      years, to evaluate the hygienic quality of ready-to-eat foods, prepared and
      served in a hospital catering service, and the microbiological status of food
      contact surfaces. Food hygiene was evaluated using non-pathogenic indicator
      microorganisms. The study was part of the verification activities that the
      hospital Health Department considers as a priority in order to guarantee patient
      safety. Only one of 52 food samples tested was considered unsatisfactory; the
      examined surfaces were not fully satisfactory in one of four cases. The study
      results, although encouraging as a whole, especially with respect to the hygienic
      safety of food prepared and served in the hospital, confirm the need to
      continuously verify that the appropriate environmental sanitation procedures are
      applied, even in the case of outsourcing. Considering the increased
      susceptibility of hospitalized patients, this remains a priority in the hospital
      where the study was performed.

PMID- 29573386
TI  - [Lying in dementia care].
AB  - The indiscriminate use of lying, when communicating with patients with dementia,
      is questioned in terms of ethics and acceptability. In this article we present
      the concept of "therapeutic lying", to describe those situations where a "non
      truth" is used in the patient's interest and not that of the healthcare
      professional. The debate is still open, so it is necessary to better clarify
      risks and benefits of lying in the context of care, both to safeguard patients
      and to allow healthcare professionals to respect ethical and moral standards.

PMID- 29573387
TI  - [Prevalence of Obstructive Sleep Apnea Syndrome among holders of a category B
      driver's license and among professionals in the Province of Pesaro-Urbino
      (Italy)].
AB  - Obstructive Sleep Apnea Syndrome (OSAS) is a sleeping disorder caused by repeated
      episodes of partial or complete obstruction of the upper airways during sleep.
      During 2013, a pilot project was performed in the Marche region (Italy), co
      jointly by the University "Politecnica delle Marche" and the Italian National
      Institute of Work Accident Insurance (INAIL), among holders of a category "B"
      driver's licence and among professionals undergoing screening at an Occupational
      Medicine Service covering the Province of Pesaro-Urbino (Italy). Nineteen percent
      of 553 subjects undergoing a screening examination were found to be affected by
      OSAS. The data collected is of great interest in the phase of implementation of
      new national laws.

PMID- 29573388
TI  - [The burden of informal caregivers of multiple sclerosis patients: a pilot
      study].
AB  - AIM: The main objective of the study was to measure caregiver burden among
      informal caregivers assisting people with multiple sclerosis (MS). BACKGROUND:
      Thirty percent of people with multiple sclerosis require some form of home
      assistance and 80% of such care is provided by informal caregivers. The quality
      of life of informal caregivers of patients with multiple sclerosis decreases with
      increasing physical and depressive symptoms of their loved ones. This can have
      effects on stress levels, physical and mental health, quality of life, and
      mortality of informal caregivers. DESIGN: A descriptive correlational study was
      performed in a sample of informal caregivers of MS patients. METHODS: The study
      enrolled 41 informal caregivers of MS patients at a regional reference center in
      Rome, Italy. Data collection took place in the period between May and September
      2016. A paper questionnaire was used, comprising a socio-demographic section and
      a "Caregiver Burden Inventory" section. RESULTS: The subjective burden perceived
      by informal caregivers of patients with MS is moderate. Socio-demographic
      characteristics were not found to influence burden of caregivers. CONCLUSIONS: It
      is important for nursing professionals to consider and evaluate the burden of
      informal caregivers of MS patients as they are valuable allies in the management
      of these patients.

PMID- 29573389
TI  - [Incidence of biological accidents at work and immune status for vaccine
      preventable diseases among resident physicians in specialist training at Ferrara
      University Hospital].
AB  - The hospital as a work environment is particularly characterized by various risks
      for healthcare workers (HCWs). The main risk is represented by biological
      accidents, associated with the parenteral transmission of pathogens. Biological
      injuries can occur during the care service and the manipulation of biological
      fluids. Hepatitis B (and hepatitis D), hepatitis C and HIV are the most common
      infections transmitted by biological injuries. Physicians should acquire
      awareness of the risks associated with their professional activity during their
      training as medical residents (MRs). Some infectious diseases are preventable by
      vaccination and the "National Immunization Plan 2017-2019" (PNPV) recommends HCWs
      vaccination against hepatitis B, influenza, measles -mumps -rubella, chicken pox,
      and pertussis. Besides, not only HCWs' vaccination can prevent the disease in
      healthcare professionals, but it also may reduce the transmission to patients.
      Therefore, active immunization of HCWs by recommended vaccinations plays an
      important role to prevent disease cases, complications and death in patients. An
      increased awareness of risk behaviors is the first important point to address in
      order to reduce biological accidents and infectious diseases transmission, so as
      to reduce their frequency. Besides, HCWs' vaccination is useful to reinforce
      protection and to prevent the transmission of some infectious diseases in case of
      exposure. The aim of this five-year incidence study is to investigate the MRs'
      biological accidents characteristics and to analyze the MRs' immune status at the
      University of Ferrara in the period 2011-2015. Data on MRs' biological accidents
      and immune status at Azienda Ospedaliero-Universitaria of Ferrara in 2011-2015
      were analyzed by Microsoft Excel 2007 Software. In this study, the percentage of
      MRs' biological injuries compared to the total number of MRs showed an annual
      variability, with a peak in 2011 (11.9%). During the analyzed period, there were
      190 biological injuries among the MRs: 81% were percutaneous injuries and blood
      was the biological fluid involved in 86.3% of cases. The most frequent lesion was
      puncture (62.6%), occurred in 41.1% of cases by suture needles; 46.3% of
      accidents occurred in the operating block. These data can be explained by the
      more invasive and at risk activities carried out in these Operative Units. The
      high injuries percentage in MRs may be related to less work experience and
      inadequate training or informations about personal protective equipment use.
      Among MRs, 93.7%, 93.3% and 96.6% were immune to measles, chicken pox and
      hepatitis B, respectively; only in the case of rubella, 11.9% of MRs was not
      immune. This research showed, accordingly to published data, high adhesion to
      hepatitis B vaccination. However, the healthcare workers' vaccine coverage is
      still sub-optimal; active immunization by recommended vaccines should be
      implemented for both parenteral and airborne diseases. As a matter of fact, the
      recent measles outbreak has involved healthcare workers (4689 cases of measles,
      305 in HCWs). Finally, the General Directorates of Health-care settings should
      improve healthcare personnel adhesion to vaccinations, such as influenza, by
      promotion activities in the workplace. A proposal in order to achieve coverage
      objectives could be making vaccinations mandatory, as well as already implemented
      in other countries.

PMID- 29573390
TI  - Future challenges in functional gait training for children and young adults with
      cerebral palsy.

PMID- 29573391
TI  - Interventional management of hyperhidrosis in secondary care: a systematic
      review.
AB  - BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating, which occurs at
      rest, regardless of temperature. The symptoms of hyperhidrosis can significantly
      affect quality of life. OBJECTIVES: To undertake a systematic review of the
      clinical effectiveness and safety of treatments available in secondary care for
      the management of primary hyperhidrosis. METHODS: Fifteen databases (including
      trial registers) were searched to July 2016 to identify studies of secondary-care
      treatments for primary hyperhidrosis. For each intervention randomized controlled
      trials (RCTs) were included where available; where RCT evidence was lacking,
      nonrandomized trials or large prospective case series were included. Outcomes of
      interest included disease severity, sweat rate, quality of life, patient
      satisfaction and adverse events. Trial quality was assessed using a modified
      version of the Cochrane Risk of Bias tool. Results were pooled in pairwise meta
      analyses where appropriate, otherwise a narrative synthesis was presented.
      RESULTS: Fifty studies were included in the review: 32 RCTs, 17 nonrandomized
      trials and one case series. The studies varied in terms of population,
      intervention and methods of outcome assessment. Most studies were small, at high
      risk of bias and poorly reported. The interventions assessed were iontophoresis,
      botulinum toxin (BTX) injections, anticholinergic medications, curettage and
      newer energy-based technologies that damage the sweat gland. CONCLUSIONS: The
      evidence for the effectiveness and safety of treatments for primary hyperhidrosis
      is limited overall, and few firm conclusions can be drawn. However, there is
      moderate-quality evidence to support the use of BTX for axillary hyperhidrosis. A
      trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.

PMID- 29573393
TI  - Automated scoring of vitiligo using superpixel-generated computerized digital
      image analysis of clinical photographs: a novel and consistent way to score
      vitiligo.

PMID- 29573392
TI  - Patterns of dopamine transporter imaging in subtypes of multiple system atrophy.
AB  - OBJECTIVES: To investigate the differences in the pattern of striatal (caudate
      and putamen) dopamine transporter (DAT) loss in a multiple system atrophy (MSA)
      cohort, based on the clinical variants parkinsonian subtype (MSA-P) and
      cerebellar subtype (MSA-C) via (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane
      (11 C-CFT) positron emission tomography (PET) imaging. MATERIALS AND METHODS: One
      hundred and six subjects (forty-one patients with probable MSA-P; forty patients
      with probable MSA-C; twenty-five healthy controls) underwent 11 C-CFT PET.
      Subregional 11 C-CFT uptake of bilateral caudate, anterior putamen, and posterior
      putamen was calculated respectively to measure the striatal dopaminergic
      function. RESULTS: Significant decrease in DAT binding in striatum was revealed
      in patients with MSA-C and MSA-P compared to normal controls (all regions, MSA-C
      vs controls, P < .0001; MSA-P vs controls, P < .0001). DAT reduction was more
      pronounced in MSA-P patients than that in MSA-C patients (all regions, P <
      .0001). Eleven of forty MSA-C patients displayed no DAT loss, whereas striatal
      DAT loss was evident in all MSA-P patients. MSA-P subtype showed a more obvious
      anteroposterior gradient of DAT loss and more asymmetric dopaminergic dysfunction
      compared to MSA-C patients. CONCLUSION: The subtypes of MSA studied here show
      significantly different spatial/anatomic patterns of striatonigral degeneration
      which may provide insights into their disease pathophysiology. Specifically, MSA
      P patients exhibit an uneven and much greater pronounced loss of dopamine
      innervation, while a relatively uniform pattern is revealed in patients with the
      MSA-C. Furthermore, the typical reduction in DAT 11 C-CFT binding in striatum is
      not present in all MSA-C patients, with a minority of cases showing normal DAT
      binding.

PMID- 29573394
TI  - Efficacy of oral sirolimus as salvage therapy in refractory lichen planus
      associated with immune deficiency.

PMID- 29573395
TI  - Impact of naevus association on survival for nodular and superficial spreading
      melanomas.

PMID- 29573396
TI  - Trait differences in responses to arbuscular mycorrhizal fungi are stronger and
      more consistent than fixed differences among populations of Asclepias speciosa.
AB  - PREMISE OF THE STUDY: Arbuscular mycorrhizal (AM) fungi can promote plant growth
      and reproduction, but other plant physiological traits or traits that provide
      defense against herbivores can also be affected by AM fungi. However, whether
      responses of different traits to AM fungi are correlated and whether these
      relationships vary among plants from different populations are unresolved.
      METHODS: In a common garden experiment, we grew Asclepias speciosa plants from
      seed collected from populations found along an environmental gradient with and
      without AM fungi to assess whether the responses of six growth and defense traits
      to AM fungi are correlated. KEY RESULTS: Although there was strong genetic
      differentiation in mean trait values among populations, AM fungi consistently
      increased expression of most growth and defense traits across all populations.
      Responses of biomass and root to shoot ratio to AM fungi were positively
      correlated, suggesting that plants that are more responsive to AM fungi allocated
      more biomass belowground. Responses of biomass and trichome density to AM fungi
      were negatively correlated, indicating a trade-off in responsiveness between a
      growth and defensive trait. CONCLUSIONS: Our results suggest that while there is
      substantial population differentiation in many traits of A. speciosa, populations
      respond similarly to AM fungi, and both positive and negative correlations among
      trait responses occur.

PMID- 29573397
TI  - Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies in children with
      acquired demyelinating syndromes.

PMID- 29573399
TI  - Cerebrovascular autoregulation monitoring and patient-centred outcomes after
      cardiac surgery: a systematic review.
AB  - BACKGROUND: Impaired cerebrovascular autoregulation (CVAR) is observed in up to
      20% of cardiac surgical patients. This systematic review aims to evaluate the
      association between impaired CVAR, measured by current monitoring techniques, and
      patient-centred outcomes in adults following cardiac surgery. METHODS: MEDLINE,
      EMBASE, PubMed, MEDLINE In-Process and Cochrane Library were systematically
      searched through 8 December 2017. Studies were included if they assessed
      associations between CVAR and patient-centred outcomes in the adult cardiac
      surgical population. The primary outcome of this systematic review was mortality.
      Secondary outcomes were stroke, delirium and acute kidney injury. Risk of bias
      was systematically assessed, and the GRADE methodology was used to evaluate the
      quality of evidence across outcomes. RESULTS: Eleven observational studies and no
      randomised controlled trials met the inclusion criteria. Due to methodological
      heterogeneity, meta-analysis was not possible. There was a high risk of bias
      within individual studies and low quality of evidence across outcomes. Of the
      included studies, one assessed mortality, five assessed stroke, four assessed
      delirium, and three assessed acute kidney injury. No reliable conclusions can be
      drawn from the one study assessing mortality. Interpretation of studies
      investigating CVAR and stroke, delirium and acute kidney injury was complicated
      by the lack of standardisation of monitoring techniques as well as varying
      definitions of impaired CVAR. CONCLUSIONS: There is a paucity of high quality
      evidence for CVAR monitoring and its associations with outcome measures in post
      cardiac surgical patients, highlighting the need for future studies.

PMID- 29573398
TI  - Integrated and Person-Centered Care for Community-Living Older Adults: A Cost
      Effectiveness Study.
AB  - OBJECTIVES: To assess the cost-effectiveness of Embrace, an integrated primary
      care service for older adults. DATA SOURCES: Care and support claims from health
      care insurers, long-term care administration, and municipalities for enrolled
      older adults between 2011 and 2013. STUDY DESIGN: A total of 1,456 older adults,
      listed with 15 general practitioners practices in the Netherlands, were
      stratified into risk profiles ("Robust," "Frail," and "Complex care needs") and
      randomized to Embrace or care-as-usual groups. Incremental costs were calculated
      per quality-adjusted life year, per day able to age in place, and per percentage
      point risk profile improvement. PRINCIPAL FINDINGS: Total average costs were
      higher for Embrace compared to care-as-usual. Differences in health-associated
      outcomes were small and not statistically significant. Probabilities that Embrace
      is cost-effective were below 80 percent, except for "risk profile improvements"
      within risk profile "Complex care needs." Complete case analysis resulted in
      smaller differences in total average costs across conditions and differences in
      health-associated outcomes remained small. CONCLUSIONS: According to current
      standards, Embrace is not considered cost effective after 12 months. However, it
      could be considered worthwhile in terms of "risk profile improvements" for older
      adults with "Complex care needs," if society is willing to invest substantially.

PMID- 29573400
TI  - Retrospective study of perampanel efficacy and tolerability in myoclonic
      seizures.
AB  - OBJECTIVES: Perampanel is an antiepileptic drug (AED) approved for add-on
      treatment of focal seizures (with or without generalization) and primary
      generalized tonic-clonic (GTC) seizures. Our objective was to explore the
      effectiveness and tolerability of adjunctive perampanel in patients with drug
      resistant myoclonic seizures, after failure of other AEDs. MATERIALS AND METHODS:
      Retrospective, multicenter, observational study. Data were collected from
      individual patient clinical files and analysed using appropriate descriptive
      statistics and inferential analyses. RESULTS: Data are reported for 31 patients
      with mean age 36.4 years, who had an average epilepsy duration of 18 years,
      previously taken an average of 5.03 AEDs, and were taking an average of 2.4 AEDs
      on perampanel initiation. Patients exhibited myoclonic, GTC, absence, tonic and
      focal seizures, and most had associated cognitive decline and/or ataxia. Median
      time on perampanel was 6 months, most common dose was 6 mg, and overall retention
      rate was 84%. The responder rate for myoclonic seizures was defined via reduction
      of days with myoclonic seizures per month. At 6 months, 15 (48.4%) of the 31
      patients were classed as myoclonic seizure responders, 10 (32.3%) were myoclonic
      seizure free, and 39% saw improvements in functional ability. Of 17 patients with
      GTC seizures at baseline, 9 (53%) were responders at 6 months, and 8 (47.1%) were
      seizure free. The most frequent side effects were psychiatric disorders,
      instability, dizziness and irritability, and mostly resolved with dose reduction.
      Five patients discontinued perampanel due to side effects. CONCLUSIONS:
      Perampanel caused clinically meaningful improvements in patients with drug
      resistant myoclonic seizures. It was generally well tolerated, but psychiatric
      and neurological side effects sometimes required follow-up and dose reduction.

PMID- 29573401
TI  - Towards a new generation of participation-based interventions for adolescents
      with disabilities: the impact of the environment and the need for individual
      based designs.

PMID- 29573402
TI  - Minor neurological dysfunction and associations with motor function, general
      cognitive abilities, and behaviour in children born extremely preterm.
AB  - AIM: To study the prevalence of minor neurological dysfunction (MND) at 6 years
      of age in a cohort of children born extremely preterm without cerebral palsy (CP)
      and to investigate associations with motor function, cognitive abilities, and
      behaviour. METHOD: This study assessed 80 children born at less than 27 weeks of
      gestation and 90 children born at term age between 2004 and 2007 at a mean age of
      6 years 6 months. The assessments included a simplified version of the Touwen
      Infant Neurological Examination, the Movement Assessment Battery for Children,
      Second Edition (MABC-2), Wechsler Intelligence Scale for Children, Fourth Edition
      (WISC-IV), the Strengths and Difficulties Questionnaire (SDQ), and the parent
      version of the Five to Fifteen questionnaire. RESULTS: Fifty-one of the children
      born preterm had normal neurology, 23 had simple MND, and six had complex MND
      compared with 88 who had normal neurology and two simple MND in the term-born
      group (p<0.001). There were significant differences between the children with
      normal neurology and MND in the preterm group in MABC-2-assessed motor function
      (p<0.001), general cognitive abilities with WISC-IV (p=0.005), and SDQ overall
      behavioural problems and peer problems reported by the parents (p=0.021 and
      p=0.003 respectively). SDQ teacher-reported overall behavioural and hyperactivity
      problems were significantly different between children with normal and simple MND
      (p=0.036 and p=0.019). INTERPRETATION: Children born extremely preterm, in the
      absence of CP, are at risk of MND and this is associated with motor function,
      cognitive ability, and behaviour. WHAT THIS PAPER ADDS: Extremely preterm birth
      carries a risk of minor neurological dysfunction (MND). MND in children born
      extremely preterm is associated with impaired motor function and cognitive
      abilities, and behavioural problems. Male sex is associated with MND in children
      born extremely preterm.

PMID- 29573403
TI  - The clinical outcome and neuroimaging of acute encephalopathy after status
      epilepticus in Dravet syndrome.
AB  - AIM: To analyze the clinical outcome and neuroimaging over a long duration follow
      up in the currently largest series of acute encephalopathy after status
      epilepticus in patients with Dravet syndrome. METHOD: Clinical and neuroimaging
      data of patients with Dravet syndrome with a history of acute encephalopathy
      (coma >24h) after status epilepticus from February 2005 to December 2016 at
      Peking University First Hospital were reviewed retrospectively. RESULTS: Thirty
      five patients (15 males, 20 females) with a history of acute encephalopathy were
      enrolled from a total of 624 patients with Dravet syndrome (5.6%). The median
      onset age of acute encephalopathy was 3 years 1 month. The duration of status
      epilepticus varied between 40 minutes to 12 hours. Thirty-four patients had a
      high fever when status epilepticus occurred, and only one had a normal
      temperature. Coma lasted from 2 to 20 days. Twelve patients died and 23 survived
      with massive neurological regression. The median follow-up time was 2 years 1
      month. Neuroimaging of 20 out of 23 survivors during the recovery phase showed
      diverse degrees of cortical atrophy with or without subcortical lesions.
      INTERPRETATION: Acute encephalopathy after status epilepticus is more prone to
      occur in patients with Dravet syndrome who had a high fever. The mortality rate
      is high in severe cases. Survivors are left with severe neurological sequelae but
      often with either no seizure or low seizure frequency. WHAT THIS PAPER ADDS:
      Acute encephalopathy is more prone to occur in patients with Dravet syndrome with
      a high fever. The mortality rate is high for acute encephalopathy after status
      epilepticus in patients with Dravet syndrome. Survivors have neurological
      sequelae.

PMID- 29573405
TI  - Inferring the evolutionary reduction of corm lobation in Isoetes using Bayesian
      model-averaged ancestral state reconstruction.
AB  - PREMISE OF THE STUDY: Inferring the evolution of characters in Isoetes has been
      problematic, as these plants are morphologically conservative and yet highly
      variable and homoplasious within that conserved base morphology. However,
      molecular phylogenies have given us a valuable tool for testing hypotheses of
      character evolution within the genus, such as the hypothesis of ongoing
      morphological reductions. METHODS: We examined the reduction in lobe number on
      the underground trunk, or corm, by combining the most recent molecular phylogeny
      with morphological descriptions gathered from the literature and observations of
      living specimens. Ancestral character states were inferred using nonstationary
      evolutionary models, reversible-jump MCMC, and Bayesian model averaging. KEY
      RESULTS: Our results support the hypothesis of a directional reduction in lobe
      number in Isoetes, with the best-supported model of character evolution being one
      of irreversible reduction. Furthermore, the most probable ancestral corm lobe
      number of extant Isoetes is three, and a reduction to two lobes has occurred at
      least six times. CONCLUSIONS: From our results, we can infer that corm lobation,
      like many other traits in Isoetes, shows a degree of homoplasy, and yet also
      shows ongoing evolutionary reduction.

PMID- 29573404
TI  - Correlation of natural autoantibodies and cardiovascular disease-related anti
      bacterial antibodies in pericardial fluid of cardiac surgery patients.
AB  - Our previous studies showed that anti-citrate synthase (anti-CS) immunoglobulin
      (Ig)M natural autoantibodies are present in healthy individuals without previous
      antigen stimulation, but no studies have investigated their presence in the
      pericardial fluid (PF). Therefore, we detected the natural anti-CS IgG/M
      autoantibody levels in plasma and PF of cardiac surgery patients and investigated
      their relationship with cardiovascular disease-associated bacterial pathogens. PF
      and blood samples of 22 coronary artery bypass graft (CABG) and 10 aortic valve
      replacement (AVR) patients were tested for total Ig levels, natural
      autoantibodies and infection-related antibodies using enzyme-linked immunosorbent
      assay (ELISA) and Luminex methods. The B cell subsets were measured by flow
      cytometry. The total Ig subclass levels were four to eight times lower in PF than
      in plasma, but the natural anti-CS IgM autoantibodies showed a relative increase
      in PF. The frequency of CD19+ B lymphocytes was significantly lower in PF than in
      blood (P = 0.01), with a significant relative increase of B1 cells (P = 0.005).
      Mycoplasma pneumoniae antibody-positive patients had significantly higher anti-CS
      IgM levels. In CABG patients we found a correlation between anti-CS IgG levels
      and M. pneumoniae, Chlamydia pneumoniae and Borrelia burgdorferi antibody titres.
      Our results provide the first evidence that natural autoantibodies are present in
      the PF, and they show a significant correlation with certain anti-bacterial
      antibody titres in a disease-specific manner.

PMID- 29573406
TI  - T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne
      inversa: the link to hair follicle dissection, obesity, smoking and autoimmune
      comorbidities.
AB  - BACKGROUND: Disintegration of the infundibula of terminal hair follicles (HFs) in
      intertriginous skin areas exhibits the histological hallmark of hidradenitis
      suppurativa (HS)/acne inversa, featuring a dissecting terminal hair folliculitis.
      Elevated serum levels of interleukin (IL)-17 and local increase in the ratio of
      proinflammatory T helper (Th)17 cells and anti-inflammatory regulatory T cells
      (Tregs) have been reported. Perifollicular Tregs play a key role in HF stem cell
      homeostasis and infundibular integrity. OBJECTIVES: In this review, we evaluate
      the Th17/Treg ratio in HS, its aggravating conditions and associated
      comorbidities. Furthermore, we intended to clarify whether drugs with reported
      beneficial effects in the treatment of HS readjust the deviated Th17/Treg axis.
      METHODS: PubMed-listed, peer-reviewed original research articles characterizing
      Th17/Treg regulation in HS/acne inversa and associated comorbidities were
      selected for this review. RESULTS: This review presents HS as a disease that
      exhibits an increased Th17/Treg ratio. Perifollicular deficiencies in Treg
      numbers or function may disturb HF stem cell homeostasis, initiating infundibular
      dissection of terminal HFs and perifollicular inflammation. The Th17/Treg
      imbalance is aggravated by obesity, smoking and decreased Notch signalling. In
      addition, HS-associated autoimmune diseases exhibit a disturbed Th17/Treg axis
      resulting in a Th17-dominant state. All drugs that have beneficial effects in the
      treatment of HS normalize the Th17/Treg ratio. CONCLUSIONS: HS immunopathogenesis
      is closely related to deviations of the Th17/Treg balance, which may negatively
      affect Treg-controlled HF stem cell homeostasis and infundibular integrity.
      Pharmacological intervention should not only attenuate Th17/IL-17 signalling, but
      should also improve Treg function in order to stabilize HF stem cell homeostasis
      and infundibular integrity.

PMID- 29573407
TI  - Impaired muscle growth precedes development of increased stiffness of the triceps
      surae musculotendinous unit in children with cerebral palsy.
AB  - AIM: If increased muscle stiffness and contractures in children with cerebral
      palsy (CP) are related to impaired muscle growth, reduced muscle growth should
      precede or coincide with increased muscle stiffness during development. Here, we
      compared the volume of the medial gastrocnemius muscle and the passive (non
      neural) stiffness of the triceps surae musculotendinous unit in typically
      developing children and children with CP from birth until 4 years of age. METHOD:
      Forty-one children with CP and 45 typically developing children were included.
      Freehand three-dimensional ultrasound was used to evaluate the volume of the
      medial gastrocnemius muscle. Biomechanical and electrophysiological measures were
      used to determine passive and reflex mediated stiffness of the triceps surae
      musculotendinous unit. RESULTS: Medial gastrocnemius muscle volume increased with
      the same rate in typically developing and children with CP until 12 months of
      age, when a significant smaller rate of growth was observed in children with CP.
      Passive stiffness of the triceps surae musculotendinous unit showed a linear
      increase with age in typically developing children. Children with CP older than
      27 months showed a significant increase in passive stiffness. Reflex mediated
      stiffness was only pathologically increased in four children with CP.
      INTERPRETATION: The deviation of medial gastrocnemius muscle volume, earlier than
      musculotendinous unit stiffness, is consistent with the hypothesis. The data also
      point out that muscle atrophy and muscle stiffness already develops within the
      first 1 to 2 years. This emphasizes the necessity of early interventions to
      promote lower limb muscle growth in this population. WHAT THIS PAPER ADDS: Medial
      gastrocnemius muscle growth is reduced in children with cerebral palsy (CP)
      around 12 months after birth. Triceps surae musculotendinous unit stiffness is
      increased in children with CP around 27 months after birth. Reflex excitability
      is rarely increased in children with CP. Reduced muscle growth may be involved in
      the pathophysiology of contractures.

PMID- 29573408
TI  - Classic infantile Pompe patients approaching adulthood: a cohort study on
      consequences for the brain.
AB  - AIM: To examine the long-term consequences of glycogen storage in the central
      nervous system (CNS) for classic infantile Pompe disease using enzyme replacement
      therapy. METHOD: Using neuropsychological tests and brain magnetic resonance
      imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe
      patients aged up to 17 years. RESULTS: From approximately age 2 years onwards,
      brain MRI showed involvement of the periventricular white matter and centrum
      semiovale. After 8 years of age, additional white-matter abnormalities occurred
      in the corpus callosum, internal and external capsule, and subcortical areas.
      From 11 years of age, white-matter abnormalities were also found in the
      brainstem. Although there seemed to be a characteristic pattern of involvement
      over time, there were considerable variations between patients, reflected by
      variations in neuropsychological development. Cognitive development ranged from
      stable and normal to declines that lead to intellectual disabilities.
      INTERPRETATION: As treatment enables patients with classic infantile Pompe
      disease to reach adulthood, white-matter abnormalities are becoming increasingly
      evident, affecting the neuropsychological development. Therefore, we advise
      follow-up programs are expanded to capture CNS involvement in larger,
      international patient cohorts, to incorporate our findings in the counselling of
      parents before the start of treatment, and to include the brain as an additional
      target in the development of next-generation therapeutic strategies for classic
      infantile Pompe disease. WHAT THIS PAPER ADDS: In our long-term survivors treated
      intravenously with enzyme replacement therapy, we found slowly progressive
      symmetric white-matter abnormalities. Cognitive development varied from stable
      and normal to declines towards intellectual disabilities.

PMID- 29573409
TI  - The Gait Outcomes Assessment List (GOAL): validation of a new assessment of gait
      function for children with cerebral palsy.
AB  - AIM: We investigated the validity of the Gait Outcomes Assessment List (GOAL), as
      an assessment of gait function in children with cerebral palsy (CP). METHOD: We
      studied a prospective cohort of 105 children with CP (Gross Motor Function
      Classification System [GMFCS] levels I-III; 65 males, 40 females; mean [SD] age
      11y 11mo [3y 5mo], range 6-20y), who attended gait assessment over a 10-month
      period. Parents completed the GOAL, Functional Mobility Scale (FMS), and
      Functional Assessment Questionnaire (FAQ) during their child's gait evaluation.
      Ninety children completed instrumented gait analysis (IGA). Total GOAL and domain
      scores, Gait Profile Score (GPS), and Gait Variable Scores were calculated.
      RESULTS: The total GOAL discriminated between GMFCS levels (mean [SD] GMFCS level
      I, 72.5 [12.7]; GMFCS level II, 61.4 [13.0]; GMFCS level III, 38.8 [10.6]; [F2,97
      =42.4, p<0.001]). Moderate correlations were found between total GOAL and FMS (5m
      and 50m r=0.59; 500m r=0.66) and FAQ walking (r=0.77) and activities list
      (r=0.75, p<0.01). There was a moderate negative correlation between total GOAL
      and GPS (r=-0.59) and gait appearance domain and GPS (r=-0.52, p<0.01).
      INTERPRETATION: The GOAL is a valid assessment of gait function in ambulant
      children with CP. It has the potential to improve understanding of the child's
      and parents' priorities and thus, in conjunction with IGA, provide a more
      balanced assessment across the domains of the World Health Organization's
      International Classification of Functioning, Disability and Health. WHAT THIS
      PAPER ADDS: The Gait Outcomes Assessment List (GOAL) can discriminate between
      Gross Motor Function Classification System levels. The GOAL correlates with
      standard functional assessments and gait analysis. Used with gait analysis, the
      GOAL provides comprehensive assessment across all International Classification of
      Functioning, Disability and Health domains.

PMID- 29573410
TI  - Quartz-Helium Method to Estimate Fluid Flow in Thick Aquitards, Gunnedah Basin,
      Australia.
AB  - The hydraulic integrity of aquitards is generally assumed and relies on a few
      core-scale permeability measurements, drill-stem tests, or textbook values. This
      approach is because hydraulic data across the full aquitard thickness is
      generally lacking. Proper assessment of aquitard integrity should be studied at
      the formation (spanning its entire thickness at a single point) or regional
      (formation properties at multiple locations throughout the basin) scale. One
      formation-scale approach uses environmental tracers and advection-dispersion
      modeling to constrain fluid flow rates. This study demonstrates the use of helium
      concentrations in quartz as a method of constraining the rate of fluid flow in a
      520-m thick aquitard in the Gunnedah Basin, NSW, Australia. Quartz was separated
      from existing core samples in the Watermark and Porcupine Formations at depths
      from 750 to 1200 m. The helium was released from these samples by heating and
      select samples were impregnated with helium to determine the rate of helium
      diffusion through the quartz. One-dimensional advection-dispersion modeling of
      the helium profile accounting for diffusive helium exchange between quartz and
      pore water revealed, that (1) vertical fluid velocity has been on the order of
      0.02 mm/year or less for tens to thousands of years, (2) helium is in equilibrium
      between quartz and pore water, and (3) the helium profile is transient indicating
      that helium concentrations in the underlying Maules Creek Formation has varied
      over geological time. Further modeling identified aquitard conditions (thickness
      and temperature) for which equilibrium exists, a precondition for deriving
      formation-scale permeability.

PMID- 29573411
TI  - The effects of mother-child mediated learning strategies on psychological
      resilience and cognitive modifiability of boys with learning disability.
AB  - BACKGROUND: The theoretical framework of the current study is based on mediated
      learning experience (MLE) theory, which is similar to the scaffolding concept.
      The main question of the current study was to what extent mother-child MLE
      strategies affect psychological resilience and cognitive modifiability of boys
      with learning disability (LD). Secondary questions were to what extent the home
      environment, severity of boy's LD, and mother's attitude towards her child's LD
      affect her MLE strategies and consequently the child's psychological resilience
      and cognitive modifiability. AIMS: The main objectives of this study were the
      following: (a) to investigate the effects of mother-child MLE strategies on
      psychological resilience and cognitive modifiability among 7- to 10-year-old boys
      with LD, (b) to study the causal effects of distal factors (i.e., socio-economic
      status [SES], home environment, severity of child's LD, mother's attitude towards
      LD) and proximal factors (i.e., MLE strategies) on psychological resilience and
      cognitive modifiability. METHODS: A sample of mother-child dyads (n = 100) were
      videotaped during a short teaching interaction. All children were boys diagnosed
      as children with LD. The interaction was analysed for MLE strategies by the
      Observation of Mediation Interaction scale. Children were administered
      psychological resilience tests and their cognitive modifiability was measured by
      dynamic assessment using the Analogies subtest from the Cognitive Modifiability
      Battery. Home environment was rated by the Home Observation for Measurement of
      the Environment (HOME), and mothers answered a questionnaire of attitudes towards
      child's LD. RESULTS: The findings showed that mother-child MLE strategies, HOME,
      and socio-economic level contributed significantly to prediction of psychological
      resilience (78%) and cognitive modifiability (51%). Psychological resilience was
      positively correlated with cognitive modifiability (Rc = 0.67). Structural
      equation modelling analysis supported, in general, the hypotheses about the
      causal effects of distal and proximal factors of psychological resilience and
      cognitive modifiability. CONCLUSION: The findings validate and extend the MLE
      theory by showing that mother-child MLE strategies significantly predict
      psychological resilience and cognitive modifiability among boys with LD.
      Significant correlation between psychological resilience and cognitive
      modifiability calls for further research exploring the role of MLE strategies in
      development of both.

PMID- 29573412
TI  - Improved squalene production through increasing lipid contents in Saccharomyces
      cerevisiae.
AB  - Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for
      pharmacology, flavor, and biofuel industries. Microbial production of squalene
      has been of great interest due to its limited availability, and increasing prices
      extracted from animal and plant tissues. Here we report genetic perturbations
      that synergistically improve squalene production in Saccharomyces cerevisiae. As
      reported previously, overexpression of a truncated HMG-CoA reductase 1 (tHMG1)
      led to the accumulation 20-fold higher squalene than a parental strain. In order
      to further increase squalene accumulation in the tHMG1 overexpressing yeast, we
      introduced genetic perturbations-known to increase lipid contents in yeast-to
      enhance squalene accumulation as lipid body is a potential storage of squalene.
      Specifically, DGA1 coding for diacylglycerol acyltranferase was overexpressed to
      enhance lipid biosynthesis, and POX1 and PXA2 coding for acyl-CoA oxidase and a
      subunit of peroxisomal ABC transporter were deleted to reduce lipid beta
      oxidation. Simultaneous overexpression of tHMG1 and DGA1 coding for rate-limiting
      enzymes in the mevalonate and lipid biosynthesis pathways led to over 250-fold
      higher squalene accumulation than a control strain. However, deletion of POX1 and
      PXA2 in the tHMG1 overexpressing yeast did not improve squalene accumulation
      additionally. Fed-batch fermentation of the tHMG1 and DGA1 co-overexpressing
      yeast strain resulted in the production of squalene at a titer of 445.6 mg/L in a
      nitrogen-limited minimal medium. This report demonstrates that increasing storage
      capacity for hydrophobic compounds can enhance squalene production, suggesting
      that increasing lipid content is an effective strategy to overproduce a
      hydrophobic molecule in yeast.

PMID- 29573413
TI  - Herpetiform pemphigus with characteristic transmission electron microscopic
      findings of various-sized ballooning vacuoles in keratinocytes without
      acantholysis.
AB  - We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who
      had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and
      presented characteristic transmission electron microscopic (TEM) findings of
      various-sized vacuoles in keratinocytes without acantholysis. The patient
      presented with pruritic annular oedematous erythemas with small blisters lining
      the margins on the trunk and extremities. Histopathological examinations showed
      intraepidermal blisters with prominent infiltrations of eosinophils. Direct and
      indirect immunofluorescence tests revealed the presence of in vivo bound and
      circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme
      linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1-3
      showed negative results. Immunoblotting using the full-length human Dsg1
      recombinant protein showed a positive band. TEM examination showed various-sized
      vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the
      cells. Immunoelectron microscopic examination revealed IgG deposition over the
      entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies
      were also present on the inside walls of the vacuoles around the nuclei of
      keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient
      also had marked eosinophilia and high levels of thymus and activation-regulated
      chemokine and interleukin-5 in the serum. These results indicated a novel
      autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis
      of bullous spongiotic change with inflammation in HP.

PMID- 29573414
TI  - FDI-Unilever Brush Day & Night partnership: 12 years of improving behaviour for
      better oral health.
AB  - Twelve years ago, FDI World Dental Federation and Unilever Oral Care began a
      partnership to raise awareness of oral health globally. This aim reflects FDI's
      mission to "lead the world to optimal oral health", and one of the goals set by
      the Unilever Sustainable Living Plan "to improve health and well-being for more
      than 1 billion" by 2020. This partnership has developed a series of public health
      programmes to improve the brushing habits of targeted populations through health
      promotion and educational campaigns worldwide. Building on the success of the
      first two phases of the partnership, the third phase (Phase III), named Brush Day
      & Night, aimed to educate children in brushing twice-daily with fluoride
      toothpaste via a 21 Day school programme. This article reports the main outcomes
      of the past 12 years of this partnership, in particular the key outreach and
      figures of Phase III evaluation. School programmes were implemented in 10
      countries, where local teams collected data from children aged between 2 and 12
      years to monitor their oral health behaviours using specific indicators. In
      addition to the school programme, the World Oral Health Day was used as a vehicle
      to convey oral health awareness to influential governing bodies and the public.
      As a result, over 4 million people were directly reached by the programme in
      2016.

PMID- 29573415
TI  - Is grit relevant to well-being and strengths? Evidence across the globe for
      separating perseverance of effort and consistency of interests.
AB  - OBJECTIVE: Researchers conceptualize grit as the combination of two facets:
      perseverance of effort and consistency of interests toward long-term goals. We
      tested the reliability of grit facet scores across the globe and examined how
      differently each grit facet related to well-being and personality strengths.
      METHOD: An international sample of 7,617 participants from six of the seven
      continents (excluding Antarctica) completed an online survey. RESULTS:
      Confirmatory factor analyses and omega reliability coefficients indicated that
      the 12 items from the original Grit Scale were multidimensional and reliably
      measured perseverance of effort and consistency of interests. Concurrent validity
      analyses showed that perseverance of effort was moderately to strongly related to
      subjective well-being, beliefs about well-being, and personality strengths,
      whereas consistency of interests had weak or negative correlations with these
      outcomes. The stronger relations with perseverance of effort were replicated
      across seven regions of the world. The presence of overall grit was supported in
      individualistic countries, but not collectivistic countries (i.e., those in Latin
      America and Asia). CONCLUSIONS: We discuss the multidimensionality of grit,
      including a conceptual understanding of overall grit and how it may differ across
      cultures. We suggest well-being and strengths researchers study grit facets
      separately due to their differential validity.

PMID- 29573416
TI  - Is cricothyroid muscle twitch predictive of the integrity of the EBSLN in Thyroid
      Surgery?
AB  - OBJECTIVE: Cricothyroid (CT) muscle twitch inspection with neurostimulation is a
      widely accepted method to identify the external branch of the superior laryngeal
      nerve (EBSLN) and its integrity in thyroid surgery. However, there has been no
      large-scale research to evaluate the diagnostic values of CT muscle twitch
      inspection based on postoperative electromyography (EMG) results, which are
      considered the gold standard. In this study, we aimed to demonstrate the
      diagnostic value of CT muscle twitch inspection based on postoperative EMG. STUDY
      DESIGN: Prospective cohort study. METHODS: A total of 454 patients underwent
      primary thyroid surgery. Among them, 55 patients were excluded because of
      preoperative vocal fold palsy, problems with the stimulator, or refusal to
      participate in the EMG study. Finally, 399 patients were prospectively enrolled
      in this study. Intraoperatively, CT muscle twitch was inspected with
      neurostimulation. Bilateral EMG examination of the CT muscle was performed 2 to 3
      months postoperatively in all patients. RESULTS: A total of 712 EBSLNs at risk
      were analyzed in this study. Of these, 21 (2.9%) nerves were visually identified,
      and positive CT muscle twitch by neurostimulation was observed in 694 (97.5%).
      Normal results on postoperative EMG of the CT muscle were reported in 657
      (92.3%). Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were 97.7%, 5.5%, 92.5%, and 16.7%, respectively.
      CONCLUSION: CT muscle twitch inspection could be a useful intraoperative tool to
      determine EBSLN integrity considering its high sensitivity and PPV. However, the
      test may not completely replace EMG for evaluating EBSLN integrity due to its low
      specificity and NPV. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2654-2661, 2018.

PMID- 29573417
TI  - What do anti-Toxoplasma gondii IgA and IgG subclasses in human saliva indicate?
AB  - Diagnostic tests for toxoplasmosis are based on serological techniques due to
      their high sensitivity. Some IgG subclasses are related to clinical outcome in
      the congenital form. In this work, we determined the levels of IgG, IgA, IgG1,
      IgG2, IgG3 and IgG4 anti-Toxoplasma gondii antibodies in paired saliva and serum
      samples from 91 women by indirect ELISA using a crude extract of the RH strain.
      The levels of IgA, IgG2, IgG3 and IgG4 antibodies and, to a lesser extent, IgG1
      did not correlate between saliva and serum, that is, most cases that were
      positive for one Ig class in a sample were negative or very low in the other, and
      vice versa. We also observed that most samples of saliva that were positive for
      one IgG subclass were also positive for at least 2 of the other 3; this
      contrasted with findings in serum, wherein each person was positive almost
      exclusively for one subclass, as demonstrated before by us and other researchers.
      Although these findings are disappointing for the use in diagnosis, the richer
      response in saliva might indicate local exposure to T. gondii antigens without
      systemic infection; thus, saliva might be reflecting a local (protective?)
      response against this protozoan.

PMID- 29573418
TI  - Short- and long-term outcomes of oropharyngeal cancer care in the elderly.
AB  - OBJECTIVE: To examine associations between pretreatment variables, short-term and
      long-term swallowing and airway impairment, and survival in elderly patients (age
      > 65 years) treated for oropharyngeal squamous cell cancer (SCCA). STUDY DESIGN:
      Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)
      Medicare data. METHODS: Longitudinal data from 666 patients diagnosed with
      oropharyngeal SCCA from 2004 to 2007 were evaluated using cross-tabulations,
      multivariate logistic regression, and survival analysis. RESULTS: Dysphagia (odds
      ratio [OR] = 1.3, 1.0-1.7), esophageal stricture (OR = 5.5, 2.6-11.9), and airway
      obstruction (OR = 1.6, 1.1-2.2) increased 1 year after treatment. The odds of
      airway obstruction, esophageal stricture, and pneumonia increased over subsequent
      years, with significantly increased risk at 5 years for airway obstruction (OR =
      3.0, 1.4-6.4), pneumonia (OR = 4.5, 1.8-11.2), and stricture (OR = 5.5, 1.8
      17.6). Pretreatment dysphagia was a significant predictor of long-term dysphagia,
      airway obstruction, and pneumonia. Chemoradiation, advanced stage disease, high
      volume hospital care, male sex, and salvage surgery were significant predictors
      of long-term gastrostomy use. Long-term dysphagia, gastrostomy or tracheostomy
      dependence, weight loss, airway obstruction, and pneumonia were associated with
      poorer survival, with tracheostomy dependence (hazard ratio [HR] = 2.2, 1.7-2.9)
      and pneumonia (HR = 2.0, 1.7-2.4) associated with the greatest risk of late
      mortality. CONCLUSION: Airway and swallowing impairment is common after treatment
      of oropharyngeal SCCA in elderly patients, increases over time, and is associated
      with poorer survival. Patients with pretreatment dysphagia, advanced stage
      disease, initial treatment with chemoradiation, and salvage surgery represent a
      high-risk group with an increased risk of disability and death. LEVEL OF
      EVIDENCE: 2c. Laryngoscope, 128:2084-2093, 2018.

PMID- 29573420
TI  - In reference to Computed tomography image navigation patient tracker on the cheek
      during osteoplastic flaps.

PMID- 29573419
TI  - Should surgery be part of the multimodality treatment for stage IIIB non-small
      cell lung cancer?
AB  - BACKGROUND: Traditionally, treatment for stage IIIB (T4N2M0 and T1-4N3M0) NSCLC
      consists in definitive chemoradiation. Surgery is used only anecdotally. Here, we
      studied outcome for patients treated with multimodality including surgery.
      METHODS: Patients who underwent surgery for stage IIIB between 2000 and 2015 were
      retrospectively reviewed and data analyzed. Patients were selected for surgery if
      they would tolerate multimodality treatment, the tumor was deemed upfront
      resectable, and N2-N3 involvement was limited to a non-bulky single site.
      Survival was calculated from the date of surgery until last follow-up. Univariate
      and multivariate analysis were performed to identify prognostic factors. RESULTS:
      During the study period, 5416 patients underwent resection for NSCLC in our
      center. Sixty patients (1%) had clinical stage IIIB. Thirty-two patients had T4N2
      NSCLC involving the carina and/or superior vena cava (n = 25, 78%), left atrium
      (n = 5, 16%), or other (n = 2, 6%). Half of the 28 patients with N3-disease had
      supraclavicular node involvement. Pneumonectomy was performed in 27 patients
      (45%). Twenty-nine patients (48%) had induction therapy, with chemotherapy alone.
      Adjuvant therapy was administered to 52 patients (87%), mostly chemoradiation.
      Complete resection rate was 92%. Post-operative mortality was 3%. Three- and 5
      year overall survivals were 51% and 39%, respectively. Multivariate analysis
      identified incomplete resection (P = 0.008) and absence of adjuvant treatment (P
      = 0.032) as poor survival prognostic factors. CONCLUSIONS: Surgery can be
      considered as a component of multimodality therapy in highly selected patients
      with stage IIIB NSCLC based on encouraging 5-year survival of 39%.

PMID- 29573421
TI  - Extracapsular dissection for warthin tumors despite the risk of ipsilateral
      metachronous occurrence.
AB  - OBJECTIVES/HYPOTHESIS: The ideal extent of surgical intervention for
      cystadenolymphomas of the parotid gland remains a matter of controversy. The aim
      of our study was to assess the surgical outcome after extracapsular dissection
      for cystadenolymphomas of the parotid gland. A further purpose of this study was
      to examine how the number of primary cystadenolymphomas or the size of the
      primary lesion influences the possibility of an ipsilateral metachronous tumor
      occurrence. STUDY DESIGN: Retrospective clinical study. METHODS: A retrospective
      evaluation of the records was carried out for all patients treated for
      cystadenolymphomas of the parotid gland by means of extracapsular dissection at a
      tertiary referral center between 2000 and 2012. RESULTS: Three hundred twenty
      seven patients were included in the study. Our analysis detected an overall
      occurrence rate of ipsilateral metachronous tumors of 3.1% (10/327) with a mean
      follow-up of 108.4 months. A significant difference in the rate of metachronous
      lesions between unilocular (1.7%) and multilocular (11.6%) tumors could be
      detected (chi2 (1) = 7.342, P < .001). Our analysis was not able to find any
      significant influence of the maximal tumor size on the rate of metachronous
      tumors (chi2 (1) = 0.634, P = .426). CONCLUSIONS: One of the most controversial
      issues in the treatment of cystadenolymphomas of the parotid gland concerns the
      question of which is the best therapeutic approach to be taken in such patients.
      Our analysis was able to demonstrate the benefits of extracapsular dissection in
      the management of solitary as well as carefully selected multicentric
      cystadenolymphomas with a consistently acceptable surgical outcome. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 2521-2524, 2018.

PMID- 29573422
TI  - Effects of chelating agent and acids on Biodentine.
AB  - BACKGROUND: To evaluate the effect of distilled water, ethylenediaminetetraacetic
      acid (EDTA), phosphoric acid and maleic acid on Biodentine regarding surface
      topography, microhardness and push-out bond strength (POBS). METHODS: Fifty-two
      cylindrical shaped Biodentine specimens were divided into groups: control
      (distilled water); EDTA (17% EDTA); PA (37% phosphoric acid); and MA (7% maleic
      acid). Surfaces were evaluated by topographic analysis and Vickers microhardness
      test. Topographic changes were evaluated qualitatively and microhardness was
      statistically analyzed by Kruskal-Wallis test. Forty mandibular molars were used
      to simulate clinical conditions. The crowns were removed and a perforation was
      created at the furcal floor. The Biodentine was packed into the root perforations
      and the roots were divided into four groups (DW, EDTA, PA, MA). Samples were
      stored and subjected to interfacial analysis. POBS data were analyzed by Kruskal
      Wallis and Dunn tests. RESULTS: Ethylenediaminetetraacetic acid, MA and PA
      changed the morphology of the Biodentine surface. PA showed microhardness similar
      to distilled water (P > 0.05), while MA and EDTA demonstrated reduced values when
      compared with PA (P < 0.05). PA improved the POBS of Biodentine in comparison
      with the control. CONCLUSIONS: Changes in the topography, microhardness and POBS
      of Biodentine are associated with irrigant agent used.

PMID- 29573423
TI  - Toxic money or paid altruism: the meaning of payments for identity-release gamete
      donors.
AB  - Public discourses commonly frame gamete, organ and other forms of bodily donation
      as altruistic 'gifts'. However, despite on-going debates about the ethics of
      payments to donors, few studies have examined the views of donors themselves
      regarding the meaning of payments and their compatibility (or not) with
      understandings of these practices as gifts. This article addresses this issue,
      analysing 24 in-depth interviews with UK identity-release gamete donors. It was
      crucial to all participants that their donation be viewed as fundamentally other
      oriented, motivated by the desire to help others. However, whilst egg donors
      often accommodated payment within this narrative, male participants explained
      that any money would taint the gift they had given. I argue that sperm donors
      faced particular challenges to incorporating payment within a gift narrative for
      two key reasons: first, sperm donors relied on a discourse of 'pure altruism',
      including absolute opposition between gifts and market exchange, in order to
      present their donation as other-oriented. In contrast, egg donors were also able
      to mobilise a discourse of relational giving to present their donations as a
      personal gift. Second, according to a continued stereotype of sperm donors as
      financially motivated students, their payments have already been culturally
      earmarked as side-line earnings.

PMID- 29573424
TI  - Estimating heat tolerance of plants by ion leakage: a new method based on gradual
      heating.
AB  - Heat tolerance of plants related to cell membrane thermostability is commonly
      estimated via the measurement of ion leakage from plant segments after defined
      heat treatment. To compare heat tolerance of various plants, it is crucial to
      select suitable heating conditions. This selection is time-consuming and
      optimizing the conditions for all investigated plants may even be impossible.
      Another problem of the method is its tendency to overestimate basal heat
      tolerance. Here we present an improved ion leakage method, which does not suffer
      from these drawbacks. It is based on gradual heating of plant segments in a water
      bath or algal suspensions from room temperature up to 70-75 degrees C. The
      electrical conductivity of the bath/suspension, which is measured continuously
      during heating, abruptly increases at a certain temperature TCOND (within 55-70
      degrees C). The TCOND value can be taken as a measure of cell membrane
      thermostability, representing the heat tolerance of plants/organisms. Higher
      TCOND corresponds to higher heat tolerance (basal or acquired) connected to
      higher thermostability of the cell membrane, as evidenced by the common ion
      leakage method. The new method also enables determination of the thermostability
      of photochemical reactions in photosynthetic samples via the simultaneous
      measurement of Chl fluorescence.

PMID- 29573425
TI  - Cochlear implantation and auditory brainstem implantation in neurofibromatosis
      type 2.
AB  - OBJECTIVES/HYPOTHESIS: To report a series of patients with neurofibromatosis type
      2 (NF2), where each patient underwent both cochlear implantation and auditory
      brainstem implantation for hearing rehabilitation, and to discuss factors
      influencing respective implant success. STUDY DESIGN: Retrospective case series.
      METHODS: Ten NF2 patients with both cochlear implantations and auditory brainstem
      implantations were retrospectively reviewed. Speech testing for auditory
      brainstem implants (ABIs) and cochlear implants (CIs) was performed separately.
      Scores at last follow-up were obtained for Iowa vowels and consonants,
      Northwestern University Children's Perception of Speech (NU-CHIPS), and City
      University of New York (CUNY) sentences. RESULTS: Mean age at time of implant was
      37 years for cochlear implantation and 40 years for auditory brainstem
      implantation (P = .790, t test). Nine of 10 patients had a CI and ABI on
      contralateral sides, and one had both devices on the same side. Mean duration of
      deafness in the implanted ear was 4.3 years for both cochlear implantation and
      auditory brainstem implantation (P = .491, t test). Follow-up range was 1 to 28
      years. CI performance on NU-CHIPS was 32% to 100%, and sound + lip-reading CUNY
      was 56% to 100%. Four patients experienced an eventual decline in CI function to
      unusable levels. ABI performance on NU-CHIPS was 40% to 80%, and sound + lip
      reading CUNY was 38% to 94%. There was no notable decline in ABI function over
      time. CONCLUSIONS: If the cochlear nerve is intact, cochlear implantation can be
      an effective strategy for hearing rehabilitation in NF2. However, a significant
      proportion experience a decline in CI performance related to growing vestibular
      schwannoma or tumor treatment. Auditory brainstem implantation remains the
      standard option for surgical hearing rehabilitation in NF2, but peak performance
      is generally lower than that achievable with cochlear implantation. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:2163-2169, 2018.

PMID- 29573426
TI  - Ionic Liquid-Based Liquid-Liquid Microextraction for Benzodiazepine Analysis in
      Postmortem Blood Samples.
AB  - Sample preparation is rapidly improving to fulfill the need for faster and more
      environmentally friendly alternatives. In this respect, ionic liquid-based
      dispersive liquid-liquid microextraction (IL-DLLME) is an interesting technique.
      However, it has not yet been evaluated for the analysis of postmortem samples,
      which are frequently analyzed in forensic toxicology. This study investigates the
      applicability of IL-DLLME coupled to liquid chromatography-tandem mass
      spectrometry (LC-MS/MS), for the analysis of benzodiazepines in postmortem blood
      of 11 forensic cases. The method was compared with a validated solid-phase
      extraction (SPE) method. Bland-Altman analysis was performed on 24 benzodiazepine
      measurements. Both methods gave comparable results, except for flurazepam and
      temazepam (>55% difference). A feasible explanation is high postmortem matrix
      variability that was not considered during IL-DLLME validation experiments.
      Another issue could be the use of a single nondeuterated SPE internal standard.
      Overall, IL-DLLME has proven its usability for the analysis of postmortem blood.

PMID- 29573427
TI  - Transgenerational phenotype aggravation in CAF-1 mutants reveals parent-of-origin
      specific epigenetic inheritance.
AB  - Chromatin is assembled by histone chaperones such as chromatin assembly factor
      CAF-1. We had noticed that vigor of Arabidopsis thaliana CAF-1 mutants decreased
      over several generations. Because changes in mutant phenotype severity over
      generations are unusual, we asked how repeated selfing of Arabidopsis CAF-1
      mutants affects phenotype severity. CAF-1 mutant plants of various generations
      were grown, and developmental phenotypes, transcriptomes and DNA cytosine
      methylation profiles were compared quantitatively. Shoot- and root-related growth
      phenotypes were progressively more affected in successive generations of CAF-1
      mutants. Early and late generations of the fasciata (fas)2-4 CAF-1 mutant
      displayed only limited changes in gene expression, of which increasing
      upregulation of plant defense-related genes reflects the transgenerational
      phenotype aggravation. Likewise, global DNA methylation in the sequence context
      CHG but not CG or CHH (where H = A, T or C) changed over generations in fas2-4.
      Crossing early and late generation fas2-4 plants established that the maternal
      contribution to the phenotype severity exceeds the paternal contribution.
      Together, epigenetic rather than genetic mechanisms underlie the progressive
      developmental phenotype aggravation in the Arabidopsis CAF-1 mutants and
      preferred maternal transmission reveals a more efficient reprogramming of
      epigenetic information in the male than the female germline.

PMID- 29573428
TI  - The effect of postoperative steroids on post-tonsillectomy pain and need for
      postoperative physician contact.
AB  - OBJECTIVES/HYPOTHESIS: Examine the effect of postoperative steroids on
      postoperative physician contacts and determine the hemorrhage rate for patients
      taking postoperative steroids. STUDY DESIGN: Retrospective review of medical
      records. METHODS: A retrospective review was performed of children undergoing
      tonsillectomies before and after the institution of a standard postoperative
      course of three doses of dexamethasone (0.5 mg/kg). Tylenol and ibuprofen were
      also used for all patients, with oxycodone given as a rescue medication for
      children >=6 years of age. Postoperative hemorrhage rate (all visits to the
      emergency department [ED] with concern for post-tonsillectomy hemorrhage), return
      to the ED for pain, and phone calls to the office for pain were recorded.
      RESULTS: A total of 1,200 children were included (300 without and 900 with
      steroids); there was no difference in age or weight between groups. Overall, the
      mean age was 6.6 +/- 2.1 years and the hemorrhage rate was 7%. Parental phone
      calls decreased from 23.3% prior to steroid use to 14.7% after (P < .001), and
      post-tonsillectomy hemorrhage rates decreased from 9.7% to 5.7% (P = .02). There
      was no difference in ED visit rates (P = 0.70). Regression analysis showed that
      bleeding increased by 4% (95% confidence interval [CI]: 1%-13%) for each
      increasing year of age (P < .001), whereas postoperative steroids decreased
      hemorrhage rates by 7% (95% CI: 1%-9% reduction) (P = .013). The risk of a phone
      call increased by 2% for each year of age; postoperative steroids decreased phone
      calls by 9% (P < .001). There were no steroid-related complications within 1
      month of surgery. CONCLUSIONS: A short course of postoperative steroids decreased
      the number of postoperative phone calls for pain by 9% after tonsillectomy, and
      decreased the risk of postoperative tonsillectomy hemorrhage by 7%. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:2187-2192, 2018.

PMID- 29573429
TI  - Assessing nontechnical skills in otolaryngology emergencies through simulation
      based training.
AB  - OBJECTIVE: Nontechnical skills (NTS) are essential to emergency crisis
      management. Due to the rarity of true emergencies, they are challenging to teach
      and assess within a competency-based curriculum. Our purpose is to evaluate the
      utility of the Non-Technical Skills in Surgery (NOTSS) scale in NTS assessment in
      simulated otolaryngology and head and neck surgery (OTO-HNS) emergencies and
      identify common challenges that residents encounter. METHODS: Mixed methods
      analysis of 15 junior OTO-HNS resident teams in four simulated emergency
      scenarios. Six raters rated resident NTS performance using the NOTSS score.
      Constructivist-grounded theory was used to analyze scenario video transcripts to
      identify areas of learner difficulty to guide future simulation development.
      RESULTS: Residents scored highest in situational awareness and lowest in
      leadership domains. Raters showed good consistency and reliability overall
      (Cronbach's alpha = 0.885). There was no statistical difference in ratings
      between surgical experts and nonexperts. Qualitative analysis demonstrated
      challenges with closed-loop communication and handling transitions of leadership
      with the scenarios. CONCLUSION: Simulation-based training is an effective
      modality to teach NTS in crisis resource management. The NOTSS rating scale is a
      reliable instrument for assessing NTS in simulated OTO-HNS emergencies.
      Incorporating the NOTSS scale for NTS assessment within a competency-based
      curriculum is recommended. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:2301-2306,
      2018.

PMID- 29573430
TI  - Contribution of adventitious vs initial roots to growth and physiology of black
      spruce seedlings.
AB  - Black spruce (Picea mariana [Mill.] BSP) is a boreal tree species characterized
      by the formation of an adventitious root system. Unlike initial roots from seed
      germination, adventitious roots gradually appear above the root collar, until
      they constitute most of mature black spruce root system. Little is known about
      the physiological role they play and their influence on tree growth relative to
      initial roots. We hypothesized that adventitious roots present an advantage over
      initial roots in acquiring water and nutrients. To test this hypothesis, the
      absorptive capacities of the two root systems were explored in a controlled
      environment during one growing season. Black spruce seedlings were placed in a
      double-pot system allowing irrigation (25 and 100% water container capacity) and
      fertilization (with or without fertilizer) inputs independent to initial and
      adventitious roots. After 14 weeks, growth parameters (height, diameter,
      biomass), physiology (net photosynthetic rate, stomatal conductance, shoot water
      potential) and nutrient content (N, P, K, Ca and Mg foliar content) were
      compared. Most measured parameters showed no difference for the same treatment on
      adventitious or initial roots, except for root biomass. Indeed, fertilized black
      spruce seedlings invested heavily in adventitious root production, twice as much
      as initial roots. This was also the case when adventitious roots alone were
      irrigated, while seedlings with adventitious roots subjected to low irrigation
      produced initial root biomass equivalent to that of adventitious roots. We
      conclude that black spruce seedlings perform equally well through adventitious
      and initial roots, but if resources are abundant, they strongly promote
      development of adventitious roots.

PMID- 29573431
TI  - Multiscale patterns and drivers of arbuscular mycorrhizal fungal communities in
      the roots and root-associated soil of a wild perennial herb.
AB  - Arbuscular mycorrhizal (AM) fungi form diverse communities and are known to
      influence above-ground community dynamics and biodiversity. However, the
      multiscale patterns and drivers of AM fungal composition and diversity are still
      poorly understood. We sequenced DNA markers from roots and root-associated soil
      from Plantago lanceolata plants collected across multiple spatial scales to allow
      comparison of AM fungal communities among neighbouring plants, plant
      subpopulations, nearby plant populations, and regions. We also measured soil
      nutrients, temperature, humidity, and community composition of neighbouring
      plants and nonAM root-associated fungi. AM fungal communities were already highly
      dissimilar among neighbouring plants (c. 30 cm apart), albeit with a high
      variation in the degree of similarity at this small spatial scale. AM fungal
      communities were increasingly, and more consistently, dissimilar at larger
      spatial scales. Spatial structure and environmental drivers explained a similar
      percentage of the variation, from 7% to 25%. A large fraction of the variation
      remained unexplained, which may be a result of unmeasured environmental
      variables, species interactions and stochastic processes. We conclude that AM
      fungal communities are highly variable among nearby plants. AM fungi may
      therefore play a major role in maintaining small-scale variation in community
      dynamics and biodiversity.

PMID- 29573432
TI  - Molecular characterization and polymorphisms of butyrylcholinesterase in
      cynomolgus macaques.
AB  - BACKGROUND: Butyrylcholinesterase (BChE), an enzyme essential for drug
      metabolism, has been investigated as antidotes against organophosphorus nerve
      agents, and the efficacy and safety have been studied in cynomolgus macaques.
      BChE polymorphisms partly account for variable BChE activities among individuals
      in humans, but have not been investigated in cynomolgus macaques. METHODS:
      Molecular characterization was carried out by analyzing primary sequence, gene,
      tissue expression, and genetic variants. RESULTS: In cynomolgus and human BChE,
      phylogenetically closely related, amino acid residues important for enzyme
      function were conserved, and gene and genomic structure were similar. Cynomolgus
      BChE mRNA was most abundantly expressed in liver among the 10 tissue types
      analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121
      cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic,
      although none of these variants corresponded to the null or defective alleles of
      human BChE. CONCLUSIONS: These results suggest molecular similarities of
      cynomolgus and human BChE.

PMID- 29573433
TI  - Nurses' elicitation of patient error as a practice in training end-stage renal
      patients in automated home peritoneal dialysis.
AB  - As part of a reorganisation of the delivery of health care in Denmark therapies
      for chronic medical conditions are moved out of hospitals and disease-specific
      patient education programmes instituted to train patients to assume
      responsibility for treating their disease at home, that is, perform tasks and
      functions traditionally done by healthcare professionals. Drawing on video
      recordings (90:25h) from a programme for self-management of end-stage renal
      disease through automated home peritoneal dialysis, the study employs
      conversation analysis to examine nurses' instructional practices for providing
      patients with the necessary knowledge, skill and competences. Showing training to
      rely on an error-based monitoring strategy, the study demonstrates that rather
      than solely waiting for random errors to emerge, nurses on occasion steer
      patients towards specific errors to bring about particular instructional
      opportunities. Surprising given the seriousness of the therapy, this elicitation
      of error is shown to reflect a deliberate instructional choice; nurses promote
      select errors to impart patients with an understanding of the procedural logic
      behind the therapy and medical technology. The study argues that training
      patients for chronic disease self-management and providing them with a
      proficiency level, normally associated with certified professionals, necessitates
      pushing patients beyond what is strictly accurate and exposing them to medically
      delicate events.

PMID- 29573435
TI  - Comparison of cricothyroid approximation and glottoplasty for surgical voice
      feminization in male-to-female transsexuals.
AB  - OBJECTIVE: To compare voice feminization and quality of life (QoL) of Male-to
      Female Transsexuals (MtF Ts) after cricothyroid approximation (CTA) or
      glottoplasty (GL). STUDY DESIGN: Retrospective study. METHODS: Fifty-three MtF Ts
      were studied between 2007 and 2016. Voice assessment was based on fundamental
      frequency (F0 ), perceptual rating on GBRAS Hirano scale (Grade, Breathiness,
      Roughness, Asthenia, Strain), QoL related to voice on the Voice Handicap Index-10
      Spanish validated version (VHI-10 Sv) and self-perceived femininity of the voice
      (SpFv), and overall satisfaction with the surgical technique (Sst) on a visual
      analogue scale (VAS). Demographic data and complications related to surgery were
      also recorded. RESULTS: Twenty-eight MtF Ts underwent CTA and 23 GL. The mean age
      was 35 years. The median follow-up period was 40 months. Mean F0 improved after
      surgery for both groups, but this increase was 27 Hz higher after GL than after
      CTA (P < 0.05). After CTA, F0 decreased over time but remained stable after GL.
      The GBRAS score did not change after CTA; the roughness item and total score
      increased from 0 to 1 after GL (P < 0.05). VHI-10 Sv scores decreased similarly
      in both groups. SpFv increase was higher after GL. The Sst was mild and similar
      in both groups. One case of severe dysphonia (4%) resulting from a big and
      fibrous sinequia occurred after GL. CONCLUSION: Both CTA and GL increase F0 ,
      improving QoL in MtF Ts. However, F0 increase is higher and more long-lasting
      after GL. More risk of postoperative roughness is described after GL. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:2101-2109, 2018.

PMID- 29573434
TI  - The Mediating Role of Anxiety Sensitivity in Uncontrolled Drinking: A Look at
      Gender-Specific Parental Influences.
AB  - BACKGROUND: Anxiety sensitivity (AS) reflects an individual's belief that
      experiencing anxiety will cause illness or embarrassment, and may be a reason
      individuals self-medicate with alcohol. Harsh or indulgent parenting could
      contribute to the development of AS. We examined the direct and indirect
      associations between parenting styles and alcohol-related variables through AS
      and impaired control over drinking (IC; i.e., perceived failure to adhere to
      limits on alcohol consumption in the future). METHODS: A multiple-group
      structural equation model with 614 university students (344 men; 270 women) was
      examined. Structural invariance tests were conducted to evaluate moderation by
      gender. We used a bias corrected bootstrap technique to obtain the mediated
      effects. RESULTS: Father authoritarianism and mother permissiveness were directly
      linked to AS among women, whereas father permissiveness was directly linked to AS
      among men. This suggests unique parental influences based on gender regarding AS.
      While AS was directly linked to alcohol-related problems for both men and women,
      several gender-specific associations were found. AS was directly linked to IC for
      men but not for women. For men, father permissiveness was directly related to AS,
      and AS mediated the indirect link between father permissiveness and IC along both
      the heavy episodic drinking and alcohol-related problems pathways. Similar to
      other internalizing constructs (e.g., neuroticism and depression), higher AS was
      directly associated with less heavy episodic drinking but more alcohol-related
      problems. CONCLUSIONS: Our findings highlight the dangers of AS for men as an
      important correlate of under-controlled drinking behaviors. Additionally,
      permissive parenting of the same-gender parent was associated with AS, which is
      consistent with the gender-matching hypothesis. Together, these results
      underscore the importance of measuring the independent influence of both parents.

PMID- 29573436
TI  - Effects of ethrel, 1-MCP and modified atmosphere packaging on the quality of
      'Wonderful' pomegranates during cold storage.
AB  - BACKGROUND: Pomegranate (Punica granatum) is a non-climacteric fruit susceptible
      to chilling injury (CI) at temperatures below 5  degrees C. To understand the
      influences of ethylene and modified atmosphere on CI physiological disorders of
      pomegranate, exogenous ethrel (0.5, 1 and 1.5 ug L-1 ) treatments, 1
      methylcyclopropene (1-MCP) (1 uL L-1 ) exposure, packaging in a modified
      atmosphere (MAP) (XTendTM bags; StePac, Sao Paulo, Brazil), a MAP/1-MCP
      combination, and packaging in macro-perforated bags (MPB) were applied. The
      treated fruits were cold stored (2 +/- 1  degrees C; 85% relative humidity) and
      sampled during 120 + 3 days at 20  degrees C. RESULTS: During cold storage, CI
      symptoms started at 20 days in MPB and at 60 days for all exogenous ethylene
      treatments, and were delayed to 120 days in MAP, 1-MCP and MAP/1-MCP treatments.
      MPB and ethylene treatments induced significant electrolyte leakage, oxidative
      damage, lipid peroxidation, ethylene and CO2 production, and 1-aminocyclopropane
      1-carboxylic acid oxidase activity, without any change in total soluble solids,
      titratable acidity or skin and aril colours. Conversely, MAP by itself, or in
      combination with 1-MCP application, effectively delayed CI symptoms. CONCLUSION:
      During long-term cold storage of this non-climacteric fruit, ethrel application
      induced endogenous ethylene biosynthesis, accelerating the appearance of CI
      symptoms in contrast to the observations made for MAP and 1-MCP treatments. (c)
      2018 Society of Chemical Industry.

PMID- 29573437
TI  - Detection of bacteria by 16S rRNA PCR and sequencing in culture-negative chronic
      rhinosinusitis.
AB  - OBJECTIVE: Current studies on the association between bacteria and chronic
      rhinosinusitis (CRS) have relied solely on microbiological culture, which can
      sometimes be negative due to prior antibiotic therapy or lack of transport media.
      The objective of the study was to understand whether bacteria are associated with
      culture-negative cases. METHODS: We investigated 20 cases of CRS undergoing
      functional endoscopic sinus surgery by both culture and 16S rRNA gene polymerase
      chain reaction (PCR) followed by sequencing. The disease severity was assessed
      using Sino-nasal Outcome Test-22 (SNOT-22) scoring preoperatively. RESULTS: Of
      the 20 cases studied, only five were culture-positive. Bacteria were detected in
      all 15 culture-negative cases by 16S rRNA gene PCR. Sequencing indicated that
      Staphylococcus is the dominant group, followed by Enterobacter and Pseudomonas.
      In two cases, from which Pseudomonas was detected, SNOT-22 scores were above 80,
      indicating high disease severity. CONCLUSION: 16S rRNA gene PCR, followed by
      sequencing, would help the clinician understand the association between bacteria
      and CRS. Molecular detection and identification of bacteria would help the
      clinician better predict the outcome and plan further management accordingly.
      LEVEL OF EVIDENCE: NA. Laryngoscope, 128:2223-2225, 2018.

PMID- 29573438
TI  - Clinical application of chromosomal microarray analysis for the prenatal
      diagnosis of chromosomal abnormalities and copy number variations in fetuses with
      congenital heart disease.
AB  - OBJECTIVES: This study aimed to determine chromosomal abnormalities and copy
      number variations (CNVs) in fetuses with congenital heart disease (CHD) by
      chromosomal microarray analysis (CMA). METHODS: One hundred and ten cases with
      CHD detected by prenatal echocardiography were enrolled in the study; 27 cases
      were simple CHDs, and 83 were complex CHDs. Chromosomal microarray analysis was
      performed on the Affymetrix CytoScan HD platform. All annotated CNVs were
      validated by quantitative PCR. RESULTS: Chromosomal microarray analysis
      identified 6 cases with chromosomal abnormalities, including 2 cases with trisomy
      21, 2 cases with trisomy 18, 1 case with trisomy 13, and 1 unusual case of mosaic
      trisomy 21. Pathogenic CNVs were detected in 15.5% (17/110) of the fetuses with
      CHDs, including 13 cases with CHD-associated CNVs. We further identified 10 genes
      as likely novel CHD candidate genes through gene functional enrichment analysis.
      We also found that pathogenic CMA results impacted the rate of pregnancy
      termination. CONCLUSIONS: This study shows that CMA is particularly effective for
      identifying chromosomal abnormalities and CNVs in fetuses with CHDs as well as
      having an effect on obstetrical outcomes. The elucidation of the genetic basis of
      CHDs will continue to expand our understanding of the etiology of CHDs.

PMID- 29573439
TI  - Commentary on De Genna et al. (2017): Why Should We Be Concerned About Adolescent
      Mothers and Their Risks for Long-Term Risky Alcohol Consumption Over the Life
      Course?

PMID- 29573440
TI  - Do Electronic Cigarettes Have a Role in Tobacco Cessation?
AB  - Tobacco use continues to be a major cause of morbidity and mortality. Even with
      behavioral and pharmacologic treatment, long-term tobacco cessation rates are
      low. Electronic nicotine delivery systems, commonly referred to as electronic
      cigarettes or e-cigarettes, are increasingly used for tobacco cessation. Because
      e-cigarettes are widely used in this setting, health care professionals need to
      know if they are safe and effective. The purpose of this article is to review
      literature regarding use of e-cigarettes as a tool for tobacco cessation in
      patients who are ready to quit, as well as those who are not ready to quit, along
      with some selected patient populations. The safety and clinical implications of e
      cigarette use are also reviewed. Small, short-term studies assessing smokers' use
      of e-cigarettes suggest that e-cigarettes may be well tolerated and modestly
      effective in achieving abstinence. High-quality studies are lacking to support e
      cigarettes use for cessation in patients with mental health issues. One small
      prospective cohort study concluded that patients with mental health issues
      reduced cigarette use with e-cigarette use. Although one study found that
      patients with cancer reported using e-cigarettes as a tobacco-cessation strategy,
      e-cigarettes were not effective in supporting abstinence 6 and 12 months later.
      Additional research is needed to evaluate the use of e-cigarettes for smoking
      cessation in patients with pulmonary diseases. No data exist to describe the
      efficacy of e-cigarettes for smoking cessation in pregnant women. Although study
      subjects report minimal adverse effects with e-cigarettes and the incidence of
      adverse effects decreases over time, long-term safety data are lacking. Health
      care providers should assess e-cigarette use in their patients as part of the
      tobacco cessation process.

PMID- 29573441
TI  - Contemporary microbiology and identification of Corynebacteria spp. causing
      infections in human.
AB  - : The Corynebacterium is a genus of bacteria of growing clinical importance.
      Progress in medicine results in growing population of immunocompromised patients
      and growing number of infections caused by opportunistic pathogens. A new
      infections caused by new Corynebacterium species and species previously regarded
      as commensal micro-organisms have been described. Parallel with changes in
      Corynebacteria infections, the microbiological laboratory diagnostic
      possibilities are changing. But identification of this group of bacteria to the
      species level remains difficult. In the paper, we present various manual, semi
      automated and automated assays used in clinical laboratories for Corynebacterium
      identification, such as API Coryne, RapID CB Plus, BBL Crystal Gram Positive ID
      System, MICRONAUT-RPO, VITEK 2, BD Phoenix System, Sherlock Microbial ID System,
      MicroSeq Microbial Identification System, Biolog Microbial Identification
      Systems, MALDI-TOF MS systems, polymerase chain reaction (PCR)-based and
      sequencing-based assays. The presented assays are based on various properties,
      like biochemical tests, specific DNA sequences, composition of cellular fatty
      acids, protein profiles and have specific limitations. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The number of opportunistic infections caused by Corynebacteria is
      increasing due to increase in number of immunocompromised patients. New
      Corynebacterium species and new human infections, caused by this group of
      bacteria, has been described recently. However, identification of Corynebacteria
      is still a challenge despite application of sophisticated laboratory methods. In
      the study we present possibilities and limitations of various commercial systems
      for identification of Corynebacteria.

PMID- 29573442
TI  - Asbestos standards: Impact of currently uncounted chrysotile asbestos fibers on
      lifetime lung cancer risk.
AB  - BACKGROUND: Current regulations require that asbestos fibers are collected and
      examined using a light microscope. This method fails to enumerate fibers that are
      too short or thin to reliably count using a light microscope under normal
      conditions. METHODS: A cohort of 3054 workers employed at an asbestos textile
      plant was followed to ascertain causes of death. Exposure was almost entirely
      chrysotile. Fiber counts were quantified using light microscopy and electron
      microscopy. The g-formula was used to estimate impacts on lung cancer of policies
      defined in terms of fiber counts quantified using light and electron microscopy.
      RESULTS: Given exposure at the current standard, the estimated lung cancer risk
      was 7.33%, comparable to the risk expected under a standard of 1 fiber/mL counted
      using electron microscopy (7.30%). The lifetime risk of lung cancer under a
      standard of 0.1 fiber/mL counted by electron microscopy was estimated to be
      7.10%. CONCLUSIONS: We identify policies defined in terms of electron microscopy
      based asbestos exposure metrics that yield comparable, or lower, lung cancer
      mortality than that expected under the current standard.

PMID- 29573443
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis-like cutaneous
      presentation of chikungunya fever: A case series.
AB  - Chikungunya fever is a benign, self-limiting, acute viral illness. An epidemic
      occurred in New Delhi, India, in August and September 2016. We observed many
      cases with atypical cutaneous features mimicking Stevens-Johnson syndrome and
      toxic epidermal necrolysis during this epidemic, especially in infants and
      children. Twenty-one children (13 [61.9%] boys, 8 [38%] girls) presenting with
      vesico-bullous and necrotic lesions were reviewed. Cutaneous presentation
      included vesicles and bullae with purpuric macules and necrosis, seen in 16 (76%)
      patients. Skin lesions resolved in 5-7 days, leaving behind hyperpigmentation in
      seven (33.3%) patients and hypopigmentation in three (14.2%). Minor oral erosions
      were observed in three (14.2%) patients, and palmoplantar erythema was seen in
      four (19.04%). It is essential for dermatologists to understand the Stevens
      Johnson syndrome and toxic epidermal necrolysis-like presentation of chikungunya
      and not to misinterpret it as true Stevens-Johnson syndrome and toxic epidermal
      necrolysis, which will lead to unnecessary intervention and management.

PMID- 29573444
TI  - Assessment of palliative care needs of patients/families living with cancer in a
      developing country.
AB  - PURPOSE: The study seeks to assess the care needs of oncology in-patients and
      clinic attendees or families in two tertiary health institutions. METHODS: This
      was a descriptive study which utilised a quantitative survey questionnaire of all
      cancer patients diagnosed between January 2014 and September 2016 (n = 547) with
      the return rate (n = 455) representing 82%. The questionnaire explored assessment
      of palliative care need. These instruments were used, because patients with
      cancer and their families are reluctant to talk about the disease. Using a
      questionnaire was therefore the best means of obtaining their full participation.
      The data were analysed using descriptive statistics to identify the highest need
      of patients with cancer patients. The study was approved by the two participating
      hospitals and the Human and Social Sciences Research Ethics of University of
      KwaZulu-Natal. FINDINGS: The study found that most common needs of patients were
      information on possibilities of treatment and side effects (92.8%), diagnosis
      (91.6%), testing (91.1%) and physical symptoms (90.9%). There were also other
      needs, such as psychological, spiritual and financial needs, related to factors
      causing distress to patients and their families following diagnosis of cancer.
      CONCLUSIONS: This article focused on needs as expressed by patients and families
      and offers a useful guide to develop a model for integration of palliative care
      activities. The findings reveal that patients who are undergoing follow-up care
      and cancer treatment or investigation are clearly concerned about receiving
      information on a range of cancer issues. We therefore conclude that patients are
      able to deal with the disease more effectively when hospitals set up a palliative
      care team or unit to carry out proper assessment of patients living with cancer.

PMID- 29573445
TI  - Emergence of African species of dermatophytes in tinea capitis: A 17-year
      experience in a Montreal pediatric hospital.
AB  - BACKGROUND/OBJECTIVES: An increase in dermatophyte infections caused by African
      species is reported in countries receiving African immigrants. Our goal was to
      determine the epidemiologic and clinical characteristics of tinea capitis in
      children infected with African species of dermatophytes in Montreal, Canada.
      METHODS: Demographic and clinical data from medical records of children infected
      with African species of dermatophytes were retrieved retrospectively (2000-2016)
      at Sainte-Justine University Hospital Center. RESULTS: In Montreal, the number of
      tinea capitis cases caused by African species of dermatophytes increased sixfold
      over 17 years. African immigrant children (84%), men and boys (61%), and
      preschoolers (2-5 years old) (51%) were the most frequently affected in our 315
      cases. Family contamination was frequent (45%). Referring physicians prescribed
      systemic antifungal treatment in 39% of cases and pediatric dermatologist
      consultants in 90%. Treatment failure to oral terbinafine occurred in 39% of
      Microsporum audouinii infections. CONCLUSION: In Montreal, there was a
      significant increase in tinea capitis caused by African species of dermatophytes.
      Microsporum audouinii is highly transmissible and often resistant to oral
      terbinafine. Recognizing tinea capitis trends in a given environment will improve
      patient care.

PMID- 29573446
TI  - Scoliosis vertebral growth plate histomorphometry: Comparisons to controls,
      growth rates, and compressive stresses.
AB  - Scoliosis progression in skeletally immature patients depends on remaining
      growth. Relationships between vertebral growth plate histomorphometry, growth
      rates, and mechanical stresses have been reported in several animal studies.
      Hypertrophic zone heights and chondrocyte heights have been used to assess
      treatments that aim to modulate growth. The purpose of this study was to
      determine whether human vertebral physeal hypertrophic zone and cell heights
      differed between two groups: Severe scoliosis and autopsy controls. Severity was
      defined at time of surgical planning by curve magnitude and curve stiffness.
      Physeal samples were obtained from the convex side apex, and from the concave
      side when feasible. Histologic sections were prepared, and digital images were
      used to measure hypertrophic zone height, cell height, and cell width. Thirteen
      spinal deformity patients were included, mean curve magnitude 67 degrees  (+/
      23). Etiologies were juvenile and adolescent idiopathic, congenital,
      neurofibromatosis, neuromuscular, and Marfan syndrome. Five age-matched autopsy
      specimens without scoliosis served as controls. Results were presented by
      etiology, then all convex scoliosis specimens were combined and compared to
      controls. Zone heights for scoliosis, convex side, and controls were 152 um (+/
      34) and 180 um (+/-42) (p = 0.21), cell heights 8.5 um (+/-1.1) and 12.8 um (+/
      1.2) (p < 0.0005), and cell widths 14.9 um (+/-1.5) and 15.0 um (+/-2.5),
      respectively. Human values were compared to published animal models and to a
      quantitative theory of a stress  growth curve. This quantification of vertebral
      physeal structures in scoliosis may be expected to help assess theories of
      progression and potential treatments using growth modulation. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:2450-2459, 2018.

PMID- 29573447
TI  - Localized hypertrichosis of intermammary cleft in monozygotic twins.
AB  - Hypertrichosis is a condition in which hair is longer and denser than what is
      considered normal for an individual based on age, sex, ethnicity, and location on
      the body and can be classified based on its distribution (generalized vs
      localized), age of onset (congenital vs acquired), and type of hair (lanugo or
      vellus vs terminal). We describe a rare case of monozygotic female twins who
      presented for localized hypertrichosis of the intermammary cleft that developed
      during puberty. Endocrine examination was unremarkable. Discussion of various
      treatment modalities should be considered, because localized hypertrichosis may
      have a considerable psychosocial effect.

PMID- 29573448
TI  - Speckled lentiginous nevus: A rare presentation associated with motor neuropathy
      and muscular atrophy in a child.
AB  - Speckled lentiginous nevus syndrome has been described in individuals with a
      speckled lentiginous nevus with rare associated neurologic deficits. Because
      speckled lentiginous nevus syndrome almost always affects adults, it is not
      typically considered when evaluating children. We present the first reported case
      of speckled lentiginous nevus syndrome presenting in a young child with muscle
      atrophy and motor deficits affecting muscles along the same distribution as the
      speckled lentiginous nevus.

PMID- 29573449
TI  - Monoclonal antibody 7D5 recognizes the R147 epitope on the gp91phox , phagocyte
      flavocytochrome b558 large subunit.
AB  - Human phagocyte flavocytochrome b558 (Cyt b), the catalytic center of
      nicotinamide adenine dinucleotide phosphate oxidase, consists of a heavily
      glycosylated large subunit (gp91phox ; Nox2) and a small subunit (p22phox ). Cyt
      b is a membrane-spanning complex enzyme. Chronic granulomatous disease (CGD) is
      predominantly caused by a mutation in the CYBB gene encoding gp91phox on the X
      chromosome. Because the phagocytes of patients with CGD are not able to generate
      the superoxide anion, these patients are susceptible to severe infections that
      can be fatal. It has been suggested that the extracellular region of gp91phox is
      necessary for and critical to forming the epitope of mAb 7D5 and that 7D5
      provides a useful tool for rapid screening of X-linked CGD by FACS. To further
      elucidate the mAb 7D5 epitope on human gp91phox , chimeric DNA expressed human
      and mouse gp91phox recombinant protein were constructed. The fusion proteins were
      immunostained for mAb 7D5 and analyzed by FACS and western blot analysis. The 143
      ELGDRQNES151 region was found to reside at the extracellular surface on human
      gp91phox and to be an important epitope for the interaction with mAb 7D5, as
      analyzed by FACS analysis. In particular, amino acid R147 is a unique epitope on
      the membrane-associated Cyt b for mAb 7D5. In conclusion, it is proposed that
      FACS analysis using mAb 7D5 is a valuable tool for early diagnosis of CGD.

PMID- 29573450
TI  - Usefulness of ultrasonography in the diagnosis of subcutaneous granuloma
      annulare.
AB  - Subcutaneous granuloma annulare is a benign inflammatory disorder that primarily
      affects healthy children and manifests as a rapidly growing, painless, nonmobile
      mass, most commonly located in the leg. The current case highlights the
      sonographic appearance of subcutaneous granuloma annulare. Ultrasound color
      Doppler is a helpful noninvasive imaging test that may allow physicians to
      confirm the diagnosis of subcutaneous granuloma annulare and avoid unnecessary
      medical procedures.

PMID- 29573451
TI  - Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar
      cholangiocarcinoma and hepatocellular carcinoma: recommendations from the
      International Collaboration on Cancer Reporting (ICCR).
AB  - Optimal patient management benefits from comprehensive and accurate pathology
      reports that contribute to cancer staging and prognostication. Proforma reports
      are used in many countries, but these vary in their structure and implementation.
      The International Collaboration on Cancer Reporting (ICCR) is an alliance formed
      by the Royal College of Pathologists of Australasia, the Royal College of
      Pathologists of the United Kingdom, the College of American Pathologists, the
      Canadian Partnership Against Cancer the European Society of Pathology and the
      American Society of Clinical Pathology (ASCP), with the aim of developing an
      evidence-based reporting data set for each cancer site. It is argued that this
      should reduce the global burden of cancer data set development and reduplication
      of effort by different international institutions that commission, publish and
      maintain standardised cancer reporting data sets. The resultant standardisation
      of cancer reporting will benefit not only those countries directly involved in
      the collaboration but also others not in a position to develop their own data
      sets. We describe the development of a cancer data set by the ICCR expert panel
      for the reporting of the main malignant liver tumours: intrahepatic
      cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma and
      present the 'required' and 'recommended' elements to be included in the report
      with an explanatory commentary. This data set incorporates definitions and
      classifications in the most recent World Health Organisation (WHO) publication on
      hepatic malignancies (4th edition) and the recently published tumour-node
      metastasis (TNM)8 staging system. Widespread adoption and implementation of this
      data set will enable consistent and accurate data collection, comparison of
      epidemiological and pathological parameters between different populations,
      facilitate research and ultimately result in better patient outcomes.

PMID- 29573452
TI  - In-hospital outcomes comparison of transfemoral vs transapical transcatheter
      aortic valve replacement in propensity-matched cohorts with severe aortic
      stenosis.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the preferred option
      for high-risk patients with severe aortic stenosis. The preferred access for TAVR
      is transfemoral (TF). Alternatives include the transapical (TA), trans-subclavian
      (TS), and direct aortic (TAo) approaches. HYPOTHESIS: The TF approach is
      associated with lower in-hospital outcomes as well as shorter length of stay and
      lower cost of hospitalization. METHODS: The National Inpatient Sample database
      from 2012 through 2014 was used to obtain the TAVR study population.
      International Classification of Diseases, 9th Revision, Clinical Modification
      procedure codes were utilized to identify the 2 groups. In-hospital outcomes were
      compared in propensity-score-matched (1:3) cohorts, in which we took TA-TAVR as a
      control. RESULTS: A total of 8210 (weighted N = 41 050) patients were identified.
      Of these, 1622 (weighted N = 8110) patients underwent TA-TAVR and 6588 (weighted
      N = 32 940) patients underwent TF-TAVR. In-hospital mortality was lower with TF
      TAVR (4% vs 5.4%; P = 0.0355), along with a shorter length of stay (7.7 vs 9.7
      days; P < 0.0001) and lower median hospitalization cost ($64 216 vs $74 735; P <
      0.0001). Secondary outcomes of acute renal failure, transfusion, cardiogenic
      shock, and composite of all complications were lower with TF-TAVR. CONCLUSIONS:
      TF-TAVR is safer and associated with lower in-hospital outcomes compared with TA
      TAVR and should be the preferred approach. As TAVR is gaining popularity in
      intermediate- and low-risk patients, we must not lose sight of the serious
      mortality and secondary outcomes associated with TA-TAVR access.

PMID- 29573453
TI  - Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent
      PDE4 inhibitors.
AB  - A new hybrid template was designed by combining the structural features of
      phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which
      present an integral part in the skeleton of many apoptotic agents. Thirteen
      compounds of the synthesized hybrids displayed higher inhibitory activity against
      PDE4B than the reference drug, roflumilast. Further investigation indicated that
      compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre-G1
      phase, and induced cell death by apoptosis of A549 cells in a caspase-dependent
      manner.

PMID- 29573454
TI  - Determination of the occlusal vertical dimension in edentulous patients using
      lateral cephalograms.
AB  - The determination of the occlusal vertical dimension (OVD) in edentulous patients
      is based on clinical assessment with high variability. This study tested the
      hypothesis: The average OVD in edentulous patients with conventional dentures is
      too low compared to orthodontic norms, when only clinical parameters are used for
      the determination of the OVD. Edentulous patients with conventional full dentures
      were enrolled. Clinical parameters were judged by two senior prosthodontists.
      Digital lateral cephalograms were taken and served to calculate the OVD according
      to the lower face height angle (ANS-Xi-D) taking tooth-independent facial growth
      patterns into account. The ANS-Xi-D angle was compared with reference values by
      applying one-sample mean comparison tests. Thirty-six participants (17 female, 19
      male; mean age 65.3 +/- 10.6 years) were enrolled in this study. Clinically, the
      OVD of four dentures was judged too low, in one case too high, and in the other
      31 cases as correct. The mean ANS-Xi-D angle was 48.28 degrees +/-4.86 and
      statistically not different to the norm value of 49 degrees +/-4 (n.s.). There
      was a tendency that the ANS-Xi-D angle was different between participants with
      different tooth-independent facial growth patterns (ANOVA, P = .0548).
      Predominantly, clinically sufficient prostheses show adequate ANS-Xi-D angles.
      Short-face type denture patients are often restored to comply with mesiofacial
      norms. The determination of the OVD based on lateral cephalography is not
      recommendable to be a standard diagnostic parameter. Orthodontic norms are
      derived from dentate cohorts and might not take the continuing facial growth and
      other confounding factors of edentulous subjects into account.

PMID- 29573455
TI  - Comparative in vitro and in vivo effects of chlorpyrifos oxon in the outbred CD-1
      mouse (Mus musculus) and great plains toad (Anaxyrus cognatus).
AB  - We compared biochemical, functional, and behavioral responses to the
      organophosphorus anticholinesterase chlorpyrifos oxon (CPO) in mice (Mus
      musculus, CD-1) and toads (Anaxyrus cognatus, Great Plains toad). Toads were
      substantially less sensitive to acute lethality of CPO based on the maximum
      tolerated (nonlethal) dose (toads, 77 mg/kg; mice, 5.9 mg/kg). Sublethal
      exposures led to classical signs of toxicity (increased involuntary movements,
      autonomic secretions) in mice but hypoactivity in toads. Motor performance in an
      inclined plane test was not affected by CPO in mice but was altered at the
      highest dosage in toads. Acetylcholinesterase (AChE), butyrylcholinesterase,
      monoacylglycerol lipase, and fatty acid amide hydrolase activities in brain were
      inhibited in mice but not in toads, and fatty acid amide hydrolase activity in
      the liver was inhibited in both species. Toad brain AChE was less sensitive to in
      vitro inhibition by CPO (50% inhibitory concentration [IC50; 20 min, 37  degrees
      C], 101 vs 7.8 nM; IC50 [20 min, 26  degrees C], 149 vs 6.2 nM), and studies of
      inhibitor kinetics indicated substantially lower anticholinesterase potency of
      CPO against the toad brain enzyme. Using an in vitro indirect inhibition assay,
      preincubation of CPO with toad brain homogenate was more effective than an
      equivalent mouse brain homogenate at reducing CPO potency. These data suggest
      that the relatively low sensitivity of toads to cholinergic toxicity is based on
      the low sensitivity of brain AChE, which in turn may be attributable to more
      effective target-site detoxification. Environ Toxicol Chem 2018;37:1898-1906. (c)
      2018 SETAC.

PMID- 29573456
TI  - Unilateral hypertrophy of the labia minora: A case series.
AB  - Asymmetric hypertrophy of the labia minora is a variant of normal anatomy that
      has not been described in the pediatric dermatology literature. Although often
      asymptomatic, in some cases, it can cause functional, emotional, and
      psychological problems. We report the clinical characteristics and outcomes of
      four children who presented with unilateral labium minus hypertrophy. This case
      series aims to establish awareness of this condition among pediatric
      dermatologists and provide recommendations regarding management.

PMID- 29573457
TI  - Managing sleep disturbances in children with atopic dermatitis.
AB  - Atopic dermatitis is a chronic, pruritic inflammatory disease that often disrupts
      sleep in severely affected children, but there are limited studies to guide
      clinical management of these sleep problems. Disease control is crucial in
      improving sleep, but additional sleep aids may sometimes be helpful in decreasing
      scratching during the night. This review discusses the benefits and limitations
      of potential therapeutic agents available to manage sleep disturbances in
      children with atopic dermatitis.

PMID- 29573458
TI  - Solitary pigmented lesions in oral mucosa in Latin American children: A case
      series.
AB  - BACKGROUND: A variety of local and systemic processes caused exogenous and
      endogenous pigmentation of the oral mucosa. Solitary melanotic pigmentation is
      rare, hence the scarce number of studies in children and adolescents. METHODS:
      Clinical and histopathologic features of 10 Latin American children with solitary
      pigmented lesions of the oral mucosa were reviewed. RESULTS: The area most
      affected was the gingiva, followed by the palate. All lesions were flat and <1 cm
      in diameter. A brown color was observed in oral melanocytic macules and nevi. The
      exogenously pigmented lesion was bluish gray. Histopathology showed that the
      biopsied lesions corresponded to melanotic macules, junctional nevus, blue nevus,
      and exogenous pigmentation. CONCLUSION: Solitary pigmented lesions on the oral
      mucosa of children, from melanin pigment or exogenous pigment, may have a similar
      clinical presentation, but melanotic lesions such as oral melanotic macules and
      nevi can be differentiated from one another only with histopathologic
      examination.

PMID- 29573459
TI  - Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long
      term HbA1c and HbA1c variability.
AB  - AIMS: Previous evidence has demonstrated that participation in the Dose
      Adjustment for Normal Eating (DAFNE) education programme can reduce HbA1c and
      severe hypoglycaemia in people with Type 1 diabetes. In a number of studies,
      increased HbA1c variability has been associated with higher diabetic morbidity
      and mortality. No studies have examined the impact of structured education on
      HbA1c variability in Type 1 diabetes. METHODS: People with Type 1 diabetes who
      had attended DAFNE were identified for inclusion from the Scottish Care
      Information-Diabetes dataset. HbA1c median and variability, expressed as
      coefficient of variation (CV) before and after DAFNE was calculated. RESULTS:
      Some 1061 individuals participated in DAFNE education and 687 met the inclusion
      criteria. A significant median reduction in HbA1c [-3.5 mmol/mol (-0.3%)] was
      seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen
      at 60 months of follow-up. HbA1c variability as measured by CV was significantly
      lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR
      0.05-0.10); P = 0.002. CONCLUSION: The data confirm that DAFNE participation
      improves glycaemic control in Type 1 diabetes with benefits being sustained for 5
      years. This study is the first to demonstrate reduced HbA1c variability after
      completion of structured education. This is new evidence of the beneficial impact
      of DAFNE on glycaemic profile.

PMID- 29573460
TI  - Subjective oral symptoms associated with self-rated oral health among Indigenous
      groups in Central-West Brazil.
AB  - OBJECTIVES: To determine whether subjective oral symptoms were associated with
      self-rated oral health after controlling for sociodemographic characteristics and
      dentition status in 4 different Indigenous peoples from Central-West Brazil.
      METHODS: A population-based cross-sectional study of oral health was conducted
      between 2012 and 2014. The randomly selected sample was stratified according to 4
      ethnic groups (Kaiwoa, Kadiweu, Terena and Guarani) and 2 age groups (15-19 and
      35-44 years). The outcome was poor self-rated oral health. Independent variables
      obtained by interviews were age, sex, ethnicity, schooling, family income, self
      reported toothache, difficulty chewing and difficulty speaking due to dental
      problems. Dentition status, oral morbidity and normative treatment needs were
      obtained through oral examinations. Unadjusted and adjusted prevalence ratios
      (PR) and respective 95% confidence intervals (CI) were estimated using Poisson
      regression modelling with robust variance estimation. RESULTS: Poor self-rated
      oral health was more common in the older age group and in Guarani peoples than
      their counterparts (PR = 1.06 [1.00-1.12]; PR = 1.09 [1.02-1.16], respectively).
      After adjusting for sociodemographic characteristics, fewer functional teeth (PR
      = 1.11 [1.02-1.20]), 2 or more untreated decayed teeth (PR = 1.15 [1.07-1.23]),
      normative need for extraction (PR = 1.15 [1.05-1.25]) and normative need for
      restoration of one or more surfaces (PR = 1.16 [1.05-1.27]) were positively
      associated with self-rated oral health. Toothache and difficulty speaking
      remained positively associated with the outcome after controlling for all
      previous variables (PR = 1.10 [1.05-1.18]; PR = 1.20 [1.09-1.32]). CONCLUSIONS:
      Oral symptoms such as toothache and difficulty speaking due to dental problems
      play an important role in oral health self-rating. Self-rated oral health is an
      appropriate indicator for use in diverse sociocultural contexts.

PMID- 29573461
TI  - Health system organizational reform in governing Iranian public hospitals: A
      content analysis to comprehend the barriers in Board of Trustees' hospitals.
AB  - BACKGROUND: Since the early 1990s, Iran has initiated structural and
      decentralization reforms in the hospital system. This policy led to the formation
      of a Board of Trustees (BOTs) for the governing of public educational hospitals
      and making important modifications in hospitals' financing. This study was
      conducted to identify the barriers in implementing this policy. METHODS: All the
      Iranian Medical Sciences Universities and hospitals involved in the policy
      implementation were included in this qualitative study. The data were analyzed by
      using content analysis. RESULTS: In total, 403 problems were divided into 9
      classes including problems related to implementing regulation, financial problems
      in policy implementation, problems related to faculty members, ambiguity in
      executive regulation, problems related to the BOTs, authority level, hospital
      structure, the quality and quantity of hospital human resources, and fee for
      services. CONCLUSION: It appears that "implementing regulation" and "financial
      problems" embrace over 50% of the barriers. Apparently, the new approach to
      hospitals' autonomy has not achieved the desired goals. Considering the
      contextual factor, the evidence and identification of the clear role of various
      stakeholders should be essential determinants. Partial implementation of this
      policy without paying attention to the other aspects would end in failure. The
      results showed insufficient budget to be the most influential factor that posed a
      dilemma in implementing the BOTs' policy. However, BOTs in Iranian health system
      need to strive toward a higher level of performance that will improve
      effectiveness and efficiency now more than ever.

PMID- 29573462
TI  - University of Wisconsin vs normal saline solutions for preservation of blood
      vessels of brain dead donors: A histopathological study.
AB  - OBJECTIVE: To compare the cellular changes of harvested arteries which were
      preserved in normal saline (NS) and the standard and routinely used University of
      Wisconsin (UW) solution. METHODS: This experimental study was conducted on 20
      brain dead patients. The femoral and iliac arteries were bilaterally removed and
      were placed in NS and UW solutions. The vascular change indices including
      endothelial detachment (ED), medial detachment (MD), and internal elastic
      membrane disruption (IEMD) were surveyed for each preserver in the first, 5th,
      10th, and 21st day. RESULTS: The mean age of the included patients was 32.28 +/-
      8.88 years, and there were 13 (65.0%) men and 7 (35.0%) women among the patients.
      The NS and UW preservation solutions were comparable regarding the indices of
      vascular changes at first, 5th, and 10th day of the study. Only in 21st day of
      the study, there was a significant difference between 2 group regarding MD
      changes (P = .049). CONCLUSION: The results of this in vitro study demonstrated
      that NS can be used as a worthy preserver for harvested vessels for up to 21
      days, especially in resource-limited transplantation centers.

PMID- 29573463
TI  - Decomposing inequality in financial protection situation in Iran after
      implementing the health reform plan: What does the evidence show based on
      national survey of households' budget?
AB  - BACKGROUND: Lack of well-designed healthcare financing mechanisms and high level
      of out-of-pocket payments in Iran over the last decades led to implementing
      Health Transformation Plan, in 2014. This study aims to decompose inequality in
      financial protection of Iranian households after the implementation of the Health
      Transformation Plan. METHODS: The data of Statistical Center of Iran (SCI) Survey
      on Rural and Urban Households Income-Expenditure in 2015 to 2016 were used. The
      headcount ratio of catastrophic health expenditures was calculated. The corrected
      concentration index was estimated. The role of contributors on inequality in the
      exposure to catastrophic health expenditures among poor and nonpoor households
      was calculated using Farelie's model. RESULTS: The headcount ratio of the
      exposure to catastrophic health expenditures in urban and rural households was
      2.5% (2.43% - 2.64%) and 3.6% (3.48% - 3.76%), respectively. The difference in
      households' income levels was the main contributor in explaining the inequality
      in facing catastrophic health expenditures between poor and nonpoor households.
      [Correction added on 02 June 2018, after first online publication: The "Results"
      section of the Abstract of the published article has been correctly updated on
      this version.] CONCLUSION: Even after implementing the HTP, the headcount ratios
      of catastrophic health expenditure are still considerable. The results show that
      income is the greatest determinant of inequality in facing catastrophic health
      expenditure and in urban households.

PMID- 29573464
TI  - Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal
      transition modulated by pseudopodial actin dynamic in human colorectal cancer.
AB  - Kinesin family member 20B (KIF20B) has been reported to have an oncogenic role in
      bladder and hepatocellular cancer cells, but its role in colorectal cancer (CRC)
      progression remains unclear. In this study, we assessed the mRNA and protein
      levels of KIF20B in CRC tissues using qRT-PCR and immunohistochemistry,
      respectively. KIF20B was overexpressed in CRC tissues and was associated with
      cancer invasion and metastasis. Mechanistically, KIF20B overexpression promoted
      the epithelial-mesenchymal transition (EMT) process mediated by glioma-associated
      oncogene 1 (Gli1) as well as CRC cell migration and invasion. Interestingly,
      KIF20B was localized in pseudopod protrusions of CRC cells and influenced the
      formation of cell protrusions, especially the EMT-related invadopodia. Moreover,
      intracellular actin dynamic participated in the modulation of the Gli1-mediated
      EMT and EMT-related cell pseudopod protrusion formation induced by KIF20B. We
      identified a role for KIF20B in CRC progression and revealed a correlation
      between KIF20B expression in CRC tissues and patient prognosis. The underlying
      mechanism was associated with the Gli1-mediated EMT and EMT-related cell
      protrusion formation modulated by intracellular actin dynamic. Thus, KIF20B may
      be a potential biomarker and promising treatment target for CRC.

PMID- 29573465
TI  - Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.
AB  - Irradiation exposure positive correlates with tumor formation, such as breast
      cancer and lung cancer. However, whether low dose irradiation induces
      hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the
      present study, we reported that low dose irradiation facilitated the
      proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low
      dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion
      of heightened HULC erased the cells growth accelerated following low dose
      irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by
      overexpression of HULC following low dose irradiation exposure via complementary
      base pairing, resulting in promoting cell cycle process. Thus, our findings
      provide new insights into the mechanism of low dose irradiation-induced
      hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the
      potential risk of low dose irradiation for the development of hepatocellular
      carcinoma in pre-clinical settings.

PMID- 29573466
TI  - Functional characterization of salt-tolerant microbial esterase WDEst17 and its
      use in the generation of optically pure ethyl (R)-3-hydroxybutyrate.
AB  - The two enantiomers of ethyl 3-hydroxybutyrate are important intermediates for
      the synthesis of a great variety of valuable chiral drugs. The preparation of
      chiral drug intermediates through kinetic resolution reactions catalyzed by
      esterases/lipases has been demonstrated to be an efficient and environmentally
      friendly method. We previously functionally characterized microbial esterase
      PHE21 and used PHE21 as a biocatalyst to generate optically pure ethyl (S)-3
      hydroxybutyrate. Herein, we also functionally characterized one novel salt
      tolerant microbial esterase WDEst17 from the genome of Dactylosporangium
      aurantiacum subsp. Hamdenensis NRRL 18085. Esterase WDEst17 was further developed
      as an efficient biocatalyst to generate (R)-3-hydroxybutyrate, an important
      chiral drug intermediate, with the enantiomeric excess being 99% and the
      conversion rate being 65.05%, respectively, after process optimization. Notably,
      the enantio-selectivity of esterase WDEst17 was opposite than that of esterase
      PHE21. The identification of esterases WDEst17 and PHE21 through genome mining of
      microorganisms provides useful biocatalysts for the preparation of valuable
      chiral drug intermediates.

PMID- 29573467
TI  - Electrocardiographic changes before and after successful kidney transplantation
      and associations with cardiovascular and mortality outcomes.
AB  - INTRODUCTION: Electrocardiographic (ECG) changes before and after kidney
      transplantation are not well-defined. Our aim was to describe the evolution of
      ECG in patients on dialysis before and after successful kidney transplantation
      and to explore the association between ECG findings and major cardiovascular (CV)
      events and mortality after kidney transplantation. PATIENTS AND METHODS:
      Electrocardiographics were collected retrospectively 3 times: at entry to the
      transplantation waiting list, at transplantation, and 1 year after the
      transplantation from 212 kidney transplantation recipients. Altogether 19 ECG
      variables were analyzed. RESULTS: Left ventricular hypertrophy was present in
      10.2% by the Cornell voltage-duration product criteria and 10.7% by the Sokolow
      Lyon voltage criteria before kidney transplantation. The presence of ST
      depression (OR 3.12, 95% CI 1.12 -8.7 and P = .03) at entry to the waiting list
      and Q wave at the time of transplantation (OR 3.28, 95% CI 1.06-10.10 and P =
      .04) were both independently associated with major CV events after the
      transplantation. In addition, the presence of Q wave at entry to the waiting list
      was a risk factor of premature death after the transplantation (OR 2.92, 95% CI
      1.06-8.05 and P = .04). DISCUSSION: Careful analysis of the ECG before
      transplantation can be used to estimate cardiovascular events and mortality risk
      after kidney transplantation.

PMID- 29573468
TI  - Line-assisted complete closure for a large mucosal defect after colorectal
      endoscopic submucosal dissection decreased post-electrocoagulation syndrome.
AB  - BACKGROUND AND AIM: The incidence of post-endoscopic submucosal dissection (ESD)
      coagulation syndrome (PECS) can be decreased by closing mucosal defects. However,
      large mucosal defects after colorectal ESD cannot be closed endoscopically. We
      established line-assisted complete clip closure (LACC), a novel technique for
      large mucosal defects after colorectal ESD. We evaluated the prophylactic
      efficacy of LACC for preventing PECS. METHODS: Sixty-one consecutive patients on
      whom LACC after colorectal ESD was attempted from January 2016 to August 2016
      were analyzed. After exclusion of patients with incomplete LACC and adverse
      events during ESD, 57 patients comprised the LACC group. In contrast, 495
      patients who did not undergo closure of a mucosal defect comprised the control
      group. Propensity score matching was used to adjust for patients' backgrounds.
      Treatment outcomes were evaluated between the groups. RESULTS: Median resected
      specimen size in the LACC-attempted group was 35 mm (range, 20-72 mm), and LACC
      success rate was 95% (58/61). Median procedure time of LACC was 14 min. In the
      LACC group, incidence of PECS was only 2%, and no delayed bleeding or perforation
      occurred. Propensity score matching created 51 matched pairs. Adjusted
      comparisons between the LACC and control groups showed a lower incidence of PECS
      (0% vs 12%, respectively; P = 0.03) and shorter hospitalization (5 vs 6 days,
      respectively; P < 0.001) in the LACC group. CONCLUSION: This study suggests that
      LACC can effectively reduce the incidence of PECS, although further large-scale
      studies are warranted.

PMID- 29573469
TI  - Strengths and challenges in conducting clinical trials in Parkinson's disease
      mild cognitive impairment.
AB  - Treatments to slow the progression of cognitive dysfunction to dementia and
      improve the quality of life of persons with Parkinson's disease (PD) are
      desperately needed. Because PD mild cognitive impairment is considered a
      transitional stage before dementia, it opens a window to timely intervention.
      This article critically reviews the strengths and challenges of pharmacologic and
      nonpharmacologic clinical therapeutic trials in PD mild cognitive impairment
      conducted during the past 5 years, including ongoing trials. Relatively few high
      quality trials have been conducted, and some important factors in designing
      future clinical trials are discussed. (c) 2018 International Parkinson and
      Movement Disorder Society.

PMID- 29573470
TI  - TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR
      recombination: a cause for caution.
AB  - The utility of T-cell receptor (TCR) transgenic mice in medical research has been
      considerable, with applications ranging from basic biology all the way to
      translational and clinical investigations. Crossing of TCR transgenic mice with
      either recombination-activating gene (RAG)-1 or RAG-2 knockouts is frequently
      used to generate mice with a monoclonal T-cell repertoire. However, low level
      productive TCR rearrangement has been reported in RAG-deficient mice expressing
      transgenic TCRs. Using deep sequencing, we set out to directly examine and
      quantify the presence of these endogenous TCRs. Our demonstration that functional
      nontransgenic TCRs are present in nonmanipulated mice has wide reaching
      ramifications worthy of critical consideration.

PMID- 29573471
TI  - Reward learning impairment and avoidance and rumination responses at the end of
      Engage therapy of late-life depression.
AB  - OBJECTIVES: This study examined the association between reward processing, as
      measured by performance on the probabilistic reversal learning (PRL) task and
      avoidance/rumination in depressed older adults treated with Engage, a
      psychotherapy that uses "reward exposure" to increase behavioral activation.
      METHODS: Thirty older adults with major depression received 9 weeks of Engage
      treatment. At baseline and treatment end, the 24-item Hamilton Depression Rating
      Scale (HAM-D) was used to assess depression severity and the Behavioral
      Activation for Depression Scale (BADS) to assess behavioral activation and
      avoidance/rumination. Participants completed the PRL task at baseline and at
      treatment end. The PRL requires participants to learn stimulus-reward
      contingencies through trial and error, and switch strategies when the
      contingencies unexpectedly change. RESULTS: At the end of Engage treatment, the
      severity of depression was lower (HAM-D: t(19) = -7.67, P < .001) and behavioral
      activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline.
      Response time following all switches (r(19) = -0.63, P = .003) and error switches
      (r(19) = -0.57, P = .01) at baseline was negatively associated with the BADS
      avoidance/rumination subscale score at the end of Engage treatment. CONCLUSIONS:
      Impaired reward learning, evidenced by slower response following all switches and
      error switches, contributes to avoidant, ruminative behavior at the end of Engage
      therapy even when depression improves. Understanding reward processing
      abnormalities of avoidance and rumination may improve the timing and targeting of
      interventions for these symptoms, whose persistence compromises quality of life
      and increases the risk of depression relapse.

PMID- 29573472
TI  - Cardiac pheochromocytoma encasing the left main coronary artery.

PMID- 29573473
TI  - FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab
      Leads to Continued Lower Fracture Risk After Transition to Denosumab.
AB  - Romosozumab is a bone-forming agent with a dual effect of increasing bone
      formation and decreasing bone resorption. In FRActure study in postmenopausal
      woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received
      romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by
      denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year
      of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and
      reduced vertebral and clinical fractures with persistent fracture risk reduction
      upon transition to denosumab over 24 months. Here, we further characterize the
      BMD gains with romosozumab by quantifying the percentages of patients who
      responded at varying magnitudes; report the mean T-score changes from baseline
      over the 2-year study and contrast these results with the long-term BMD gains
      seen with denosumab during Fracture REduction Evaluation of Denosumab in
      Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess
      fracture incidence rates in year 2, when all patients received denosumab. Among
      7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated
      patients experienced >=3% gains in BMD from baseline at month 12 (spine, 96%;
      hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients,
      mean absolute T-score increases at the spine and hip were 0.88 and 0.32,
      respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24
      months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating
      the effect of 7 years of continuous denosumab administration. Patients receiving
      romosozumab versus placebo in year 1 had significantly fewer vertebral fractures
      in year 2 (81% relative reduction; p < 0.001), with fewer fractures consistently
      observed across other fracture categories. The data support the clinical benefit
      of rebuilding the skeletal foundation with romosozumab before transitioning to
      antiresorptive therapy. (c) 2018 The Authors. Journal of Bone and Mineral
      Research Published by Wiley Periodicals, Inc.

PMID- 29573474
TI  - Colorimetric chiral fluorescent sensors for Eu3+ and sequential enantioselective
      sensing of malate anion.
AB  - Novel phenanthroline Schiff base fluorescent sensors L1, L2, and D1 were designed
      and synthesized. The sensing abilities of the compounds in the presence of metal
      cations (Li+ , Na+ , K+ , Ag+ , Mg2+ , Ba2+ , Ca2+ , Mn2+ , Pb2+ , Hg2+ , Ni2+ ,
      Zn2+ , Cd2+ , Co2+ , Cu2+ , Cr3+ , Fe3+ , Fe2+ , Al3+ , and Eu3+ ) were studied
      by UV-vis and fluorescent spectroscopy. The compounds L1, L2, and D1 could act as
      Eu3+ ion turn-off fluorescent sensors based on ligand-to-metal binding mechanism
      in DMSO-H2 O solution (v/v = 1:1, 10 mM Tris, pH = 7.4). Additionally, the L1
      Eu3+ and D1-Eu3+ complexes could be applied as turn-on enantioselective sensors
      sensing of malate anion isomers with color changes. Furthermore, biological
      experiments using living PC-12 cells demonstrated that L1 and D1 had excellent
      membrane permeability and could be used as effective fluorescent sensors for
      detecting Eu3+ and malate anion in living cells.

PMID- 29573475
TI  - Treatment of colon cancer with liver X receptor agonists induces immunogenic cell
      death.
AB  - Liver X receptor (LXR) agonists inhibit various types of tumor growth and have
      been applied to preclinical research. In colon cancer cells, LXR agonists induce
      pyroptotic cell death through the predominant cytoplasmic localisation of
      LXRbeta. In the present study, we determined whether tumor cell death induced by
      LXR agonists in colon cancer cells could elicit immunogenic cell death (ICD). LXR
      agonist-treated-colon cancer cells exhibited translocation of calreticulin (CRT)
      and release of HMGB1 and ATP into the medium. Expression levels of CRT and HMGB1
      were also increased in T0901317-treated Balb/c mice. Furthermore, compared with
      control mice, mice vaccinated with T0901317-treated CT26 cells showed reduced
      tumor volumes and protection against a challenge with live tumor cells.
      Inhibition of CRT or HMGB1 expression in CT26 cells abolished this protection in
      Balb/c mice. In conclusion, the LXR agonist T0901317 induces ICD in colon cancer
      cells. CRT exposure and HMGB1 release play a critical role in the immunogenicity
      of this treatment.

PMID- 29573476
TI  - The multidisciplinary support in preventing alcohol relapse after liver
      transplantation: A single-center experience.
AB  - BACKGROUND AND AIM: Alcoholic liver disease (ALD) represents a frequent
      indication for liver transplantation (LT). Since 2004, we have adopted a program
      of multidisciplinary support(MS) to assist patients undergoing LT for ALD. We
      aimed at analyzing the relapse rate and the risk factors for relapse. The relapse
      rate was also compared with that of a historical group of patients who underwent
      transplantation. Their survival rate was also analyzed. PATIENTS AND METHODS:
      Consecutive patients with ALD transplanted from 2004 were included. The most
      important demographic, psychosocial, and clinical characteristics known to be
      associated with alcohol relapse were recorded. RESULTS: Sixty-nine patients
      underwent MS: 8.7% presented alcohol relapse. At multivariate analysis female
      gender (sHR 9.02, 95% CI 1.71-47.56, P = .009), alcohol withdrawal syndrome (sHR
      5.89, 95% CI 1.42-24.46, P = .015) and a shorter time of MS program before LT
      (sHR 0.928 per month, 95% CI 0.870-0.988, P = .021) were identified as
      independent risk factors for relapse. The rate of alcohol relapse was
      significantly lower than that of the historical group who did not undergo MS (sHR
      0.21, 95% CI: 0.06-0.68; P = .009). CONCLUSION: This study shows that a MS
      program may contribute to alcohol relapse prevention after LT in ALD patients.
      However, the relevance of this support needs to be confirmed by clinical trials.

PMID- 29573477
TI  - Primary cutaneous peripheral T-cell lymphoma not otherwise specified a rare and
      aggressive lymphoma.

PMID- 29573478
TI  - Gastrointestinal: Knot the intent.

PMID- 29573479
TI  - Google search trends in psoriasis: a pilot evaluation of global population
      interests.

PMID- 29573480
TI  - The role of phototherapy in the surgical treatment of vitiligo: a systematic
      review.
AB  - Vitiligo is frequently treated with the combination of phototherapy and
      melanocyte transplantation. However, the additional benefit of phototherapy is
      unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The
      objective of this systematic review was to identify whether phototherapy improves
      the outcome of melanocyte transplantation in vitiligo. We searched and screened
      for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included
      all clinical studies investigating melanocyte transplantation combined with
      phototherapy. After screening and selection of abstracts and full-texts, we found
      39 eligible clinical studies with 1624 patients. The eligible studies
      investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n =
      19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies
      directly compared phototherapy versus no phototherapy and two studies confirmed
      the benefit of phototherapy for melanocyte transplantation. We found no
      significant differences in repigmentation in studies directly comparing
      phototherapy modalities. The overall quality of the studies was moderate to poor
      and high heterogeneity between studies was found. We found limited evidence that
      phototherapy improves the outcome of melanocyte transplantation in vitiligo.
      There is insufficient evidence to recommend a specific type or regimen of
      phototherapy. More studies should be performed investigating the additional
      benefit of different phototherapies and the preferred moment of phototherapy.

PMID- 29573481
TI  - Safety profile during initiation of propranolol for treatment of infantile
      haemangiomas in an ambulatory day-care hospitalization setting.
AB  - BACKGROUND: Propranolol is the mainstay of treatment for infantile haemangioma.
      Despite its good safety profile, it is not risk-free. Guidelines for propranolol
      initiation and monitoring have been suggested, but protocols vary among
      practitioners. OBJECTIVE: This study sought to assess the prevalence of adverse
      events and clinically significant fluctuations in haemodynamic parameters in
      children with infantile haemangioma during initiation of treatment with
      propranolol in a day-hospitalization setting. METHODS: Children with infantile
      haemangioma treated with propranolol in a day-hospitalization department of a
      tertiary paediatric medical centre in 2008-2014 were identified retrospectively.
      The pretreatment evaluation included clinical examination by a paediatric
      dermatologist and electrocardiography, echocardiography and clinical examination
      by a paediatric cardiologist. The propranolol dosage was escalated from 0.5
      mg/kg/day to 2 mg/kg/day, divided into three doses/day, over 3 days. Heart rate,
      blood pressure and blood glucose level were measured before treatment onset and
      60 min after the first two doses each day. The third dose was given at home.
      RESULTS: The cohort included 220 children aged 1 month to 5 years. No severe
      treatment-related adverse events were documented; 27 patients had minor side
      effects. There was a significant decrease in heart rate each day after the first
      two doses (P < 0.001), and in systolic blood pressure, on day 2 (1 mg/kg/day)
      after the first dose (P = 0.01). Blood glucose level remained stable. The
      haemodynamic changes were clinically asymptomatic and did not require
      intervention. CONCLUSIONS: Propranolol treatment (2 mg/kg/day in three doses) for
      infantile haemangioma is well tolerated and safe and may be administered and
      monitored in an ambulatory setting.

PMID- 29573482
TI  - Screening of bioactive components from traditional Chinese medicines using cell
      membrane chromatography coupled with mass spectrometry.
AB  - INTRODUCTION: Cell membrane chromatography (CMC), as a highly selective type of
      affinity chromatography, has been demonstrated as an effective method to screen
      bioactive components acting on specific receptor from a complicated biological
      system. OBJECTIVE: To review the recent research progress and the technical
      applications of these analytical methods using CMC combined with gas
      chromatography-mass spectrometry, (GC/MS) and liquid chromatography-mass
      spectrometry (LC/MS). METHODOLOGY: In this review, we briefly introduce the CMC
      offline GC/MS, CMC online GC/MS, CMC offline LC/MS, and CMC online LC/MS system.
      And the practical application of these technologies is also enumerated. Then the
      future of these technologies and research methods were discussed. RESULTS: Many
      bioactive components interacting with specific receptors have been screened and
      identified in traditional Chinese medicines. CONCLUSION: CMC technique has been
      combined with GC/MS and HPLC/MS and these combined systems have been successfully
      used to screen bioactive components acting on specific receptors from a
      complicated biological system.

PMID- 29573483
TI  - Circular RNA expression profile analysis of severe acne by RNA-Seq and
      bioinformatics.
AB  - BACKGROUND: Acne is a common chronic skin disease with a multifactorial aetiology
      and pathogenesis. Recently, circular RNAs (circRNAs) have been identified as a
      key factor in regulating gene expression through circRNA-miRNA-mRNA networks in
      many biological processes and human diseases. However, the circRNAs expression in
      patients with acne is still unknown. OBJECTIVE: To investigate circRNA expression
      profile in severe acne. METHODS: The expression profile of circRNAs in three
      paired lesional skin and adjacent non-lesional skin in severe acne was detected
      by high-throughput RNA sequencing technology and bioinformatics analysis. The
      candidate circRNAs were validated by PCR, Sanger sequencing and qRT-PCR in the
      separate group (n = 4). The circRNA-miRNA-mRNA interaction networks were
      predicted. RESULTS: A total of 538 circRNAs including 271 up- and 267
      downregulated circRNAs were differentially expressed in lesional skin compared
      with adjacent non-lesional skin in severe acne. Gene Ontology and KEGG pathway
      enrichment analyses revealed that the aberrantly expressed circRNAs were
      primarily involved in inflammatory, metabolism and immune responses. Five
      candidate circRNAs (circRNA_0084927, circRNA_0001073, circRNA_0005941,
      circRNA_0086376 and circRNA_0018168) were validated to have significant decrease
      in severe acne by PCR, Sanger sequencing and qRT-PCR, in agreement with the
      results from RNA-Seq data analysis. The five identified circRNAs were predicted
      to interact with 213 miRNAs and regulated target gene expression. CONCLUSION:
      This study firstly showed that circRNAs were differentially expressed in severe
      acne and suggested that circRNAs could be used as a potential biomarker for the
      drug targets of acne.

PMID- 29573484
TI  - Ferrocenyl Phthalocyanine as Donor in Non-Poly(3-hexylthiophen-2,5-diyl) Bulk
      Heterojunction Solar Cell.
AB  - Bulk heterojunction (BHJ) solar cells might one day play a vital role in
      realizing low-cost and environmentally benign photovoltaic devices. In this work,
      a BHJ solar cell was designed, based on a hexadeca-substituted phthalocyanine
      (FcPc) with ferrocenyl linked to the phthalocyanine ring. Next, we sought to
      obtain more quantitative information about the usability of this newly
      synthesized compound as a donor material in BHJ solar cells. Thus, BHJs with the
      structure of indium tin oxide/poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate)/FcPc:[6,6]-phenyl-C61-butyric acid
      methyl ester (PCBM) blend/LiF/Al were fabricated and characterized. The effect of
      blend ratio (0.5-2.0) on the BHJ solar cell parameters was also investigated.
      Interesting results were obtained in FcPc and the PCBM blend-based BHJ solar cell
      under optimized conditions. Our results presented here demonstrate that BHJ
      devices employing FcPc as a donor has great potential for the development of
      highly efficient non-poly(3-hexylthiophen-2,5-diyl) photovoltaic devices.

PMID- 29573485
TI  - High-Speed 3D Printing of Millimeter-Size Customized Aspheric Imaging Lenses with
      Sub 7 nm Surface Roughness.
AB  - Advancements in three-dimensional (3D) printing technology have the potential to
      transform the manufacture of customized optical elements, which today relies
      heavily on time-consuming and costly polishing and grinding processes. However
      the inherent speed-accuracy trade-off seriously constrains the practical
      applications of 3D-printing technology in the optical realm. In addressing this
      issue, here, a new method featuring a significantly faster fabrication speed, at
      24.54 mm3 h-1 , without compromising the fabrication accuracy required to 3D
      print customized optical components is reported. A high-speed 3D-printing process
      with subvoxel-scale precision (sub 5 um) and deep subwavelength (sub 7 nm)
      surface roughness by employing the projection micro-stereolithography process and
      the synergistic effects from grayscale photopolymerization and the meniscus
      equilibrium post-curing methods is demonstrated. Fabricating a customized
      aspheric lens 5 mm in height and 3 mm in diameter is accomplished in four hours.
      The 3D-printed singlet aspheric lens demonstrates a maximal imaging resolution of
      373.2 lp mm-1 with low field distortion less than 0.13% across a 2 mm field of
      view. This lens is attached onto a cell phone camera and the colorful fine
      details of a sunset moth's wing and the spot on a weevil's elytra are captured.
      This work demonstrates the potential of this method to rapidly prototype optical
      components or systems based on 3D printing.

PMID- 29573486
TI  - The low-molecular-mass, penicillin-binding proteins DacB and DacC combine to
      modify peptidoglycan cross-linking and allow stable Type IV pilus expression in
      Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae is the causative agent of the sexually transmitted
      infection gonorrhea and is adapted to survive in humans, its only host. The N.
      gonorrhoeae cell wall is critical for maintaining envelope integrity, resisting
      immune cell killing and production of cytotoxic peptidoglycan (PG) fragments.
      Deletion of the N. gonorrhoeae strain FA1090 genes encoding two predicted low
      molecular-mass, penicillin-binding proteins (LMM PBPs), DacB and DacC,
      substantially altered the PG cross-linking. Loss of the DacB peptidase resulted
      in global alterations to the PG composition, while loss of the DacC protein
      affected a much narrower subset of PG peptide components. A double
      DeltadacB/DeltadacC mutant resembled the DeltadacB single mutant, but had an even
      greater level of cross-linked PG. While single DeltadacB or DeltadacC mutants did
      not show any major phenotypes, the DeltadacB/DeltadacC mutant displayed an
      altered cellular morphology, decreased resistance to antibiotics and increased
      sensitivity to detergent-mediated death. Loss of the two proteins also
      drastically reduced the number of Type IV pili (Tfp), a critical virulence
      factor. The decreased piliation reduced transformation efficiency and correlated
      with increased growth rate. While these two LMM PBPs differentially alter the PG
      composition, their overlapping effects are essential to proper envelope function
      and expression of factors critical for pathogenesis.

PMID- 29573487
TI  - Iron Precatalysts with Bulky Tri(tert-butyl)cyclopentadienyl Ligands for the
      Dehydrocoupling of Dimethylamine-Borane.
AB  - In an attempt to prepare new Fe catalysts for the dehydrocoupling of amine
      boranes and to provide mechanistic insight, the paramagnetic FeII dimeric complex
      [Cp'FeI]2 (1) (Cp'=eta5 -((1,2,4-tBu)3 C5 H2 )) was used as a precursor to a
      series of cyclopentadienyl FeII and FeIII mononuclear species. The complexes
      prepared were [Cp'Fe(eta6 -Tol)][Cp'FeI2 ] (2) (Tol=C6 H5 Me), [Cp'Fe(eta6 
      Tol)][BArF4 ] (3) (BArF4 =[B(C6 H3 (m-CF3 )2 )4 ]- ), [N(nBu)4 ][Cp'FeI2 ] (4),
      Cp'FeI2 (5), and [Cp'Fe(MeCN)3 ][BArF4 ] (6). The electronic structure of the
      [Cp'FeI2 ]- anion in 2 and 4 was investigated by SQUID magnetometry, EPR
      spectroscopy and ab initio Complete Active Space Self Consistent Field-Spin Orbit
      (CASSCF-SO) calculations, and the studies revealed a strongly anisotropic S=2
      ground state. Complexes 1-6 were investigated as catalysts for the
      dehydrocoupling of Me2 NH?BH3 (I) in THF at 20  degrees C to yield the
      cyclodiborazane product [Me2 N-BH2 ]2 (IV). Complexes 1-4 and 6 were active
      dehydrocoupling catalysts towards I (5 mol % loading), however 5 was inactive,
      and ultra-violet (UV) irradiation was required for the reaction mediated by 3.
      Complex 6 was found to be the most active precatalyst, reaching 80 % conversion
      to IV after 19 h at 22  degrees C. Dehydrocoupling of I by 1-4 proceeded via
      formation of the aminoborane Me2 N=BH2 (II) as the major intermediate, whereas
      for 6 the linear diborazane Me2 NH-BH2 -NMe2 -BH3 (III) could be detected,
      together with trace amounts of II. Reactions of 1 and 6 with Me3 N?BH3 were
      investigated in an attempt to identify Fe-based intermediates in the catalytic
      reactions. The sigma-complex [Cp'Fe(MeCN)(kappa2 -H2 BH?NMe2 H][BArF4 ] was
      proposed to initially form in dehydrocoupling reactions involving 6 based on ESI
      MS (ESI=Electrospray Ionisation Mass Spectroscopy) and NMR spectroscopic
      evidence. The latter also suggests that these complexes function as precursors to
      iron hydrides which may be the true catalytic species.

PMID- 29573488
TI  - Synthesis of Benzofuranones via Malonates Desymmetrization: Yield Increase by the
      Portion-wise Addition of Quinones.
AB  - The organocatalyzed addition of several malonates to 1,4-benzoquinones affords
      benzofuranones bearing a quaternary stereocenter with good enantioselectivity.
      This reaction is an intramolecular desymmetrization since it proceeds through the
      formation of an arylated achiral malonate that cyclizes to give the reaction
      product. The addition rate of the quinone dramatically affects the reaction yield
      which was originally low. The yield was considerably increased, in some cases,
      from less than 20 % to over 95 %, by adding the quinone in portions rather than
      at once, keeping similar enantioselectivity. A possible rationalization for the
      preferential formation of the indicated enantiomer has been investigated by DFT
      calculations.

PMID- 29573489
TI  - Prenatal vaginal congenital hemangiopericytoma (HPC): a rare vaginal tumor of the
      fetus.
AB  - A 29-year old gravida 2, para 1 patient presented at 22+3 weeks' of gestation
      without abnormalities detected on the first ultrasound examination. At 24+0
      weeks' gestation however, a tumor of 3x2cm potentially originating from the
      vagina was seen. The tumor's inner structure changed over time, initially
      presenting homogeneous and from 28 weeks' gestation onward inhomogeneous with
      hypoechogenic and hyperechogenic parts (Figure 1a,c).

PMID- 29573491
TI  - Generalized pustular psoriasis: a review and update on treatment.
AB  - Generalized pustular psoriasis (GPP) is a subtype of pustular psoriasis
      characterized by painful and occasionally disfiguring cutaneous manifestations
      with sepsis-like systemic symptoms. Affecting any age and race, GPP can occur
      with other forms of psoriasis or by itself. Stimuli for flares include
      medications, infections and environmental triggers. The interleukin family and
      caspase recruitment domain family have been implicated in its pathogenesis. Other
      forms of pustular psoriasis include impetigo herpetiformis, palmoplantar pustular
      psoriasis, annular pustular psoriasis and acrodermatitis continua of Hallopeau.
      Treatment is not well established, but includes the use of retinoids,
      methotrexate, cyclosporine, corticosteroids, TNF-alpha inhibitors, topical
      therapy and phototherapy. The use of TNF-alpha inhibitors may result in the
      formation of antidrug antibodies and should be administered with methotrexate.

PMID- 29573490
TI  - Extracellular matrix internalization links nutrient signalling to invasive
      migration.
AB  - Integrins are the key mediators of cell-extracellular matrix (ECM) interaction,
      linking the ECM to the actin cytoskeleton. Besides localizing at the cell
      surface, they can be internalized and transported back to the plasma membrane
      (recycled) or delivered to the late endosomes/lysosomes for degradation. We and
      others have shown that integrin can be endocytosed together with their ECM
      ligands. In this short review, I will highlight how extracellular protein
      (including ECM) endocytosis impinges on the activation of the mechanistic target
      of rapamycin (mTOR) pathway, a master regulator of cell metabolism and growth.
      This supports the intriguing hypothesis that ECM components may be considered as
      nutrient sources, primarily under soluble nutrient-depleted conditions.

PMID- 29573492
TI  - ECOSTBio: Explicit Control Over Spin States in Technology and Biochemistry.
AB  - Within the framework of the COST program, ECOSTBio is a European network of both
      experimental and theoretical researchers that tackle a diversity of chemical
      problems in which electronic spin is a key factor. In this special issue, the
      ECOSTBio researchers, as well as the invited external guests from Europe and
      abroad, highlight the importance of spin states and reactivity.

PMID- 29573493
TI  - Magnetic Interactions through a Nonconjugated Framework Observed in Back-to-Back
      Connected Triazinyl-Nitroxyl Biradical Derivatives.
AB  - Three hetero-biradical derivatives, with the structure of a back-to-back
      connected benzotriazinyl and tetramethyl or tetraethylisoindoline N-oxyl sharing
      a common benzo ring, 3-tert-butyl-1-phenyl-1,4,6,8-tetrahydro-6,6,8,8-tetramethyl
      pyrrolo[4,5-g]-1,2,4-benzotriazin-4-yl-7-oxyl (1-tBu), 1,3-diphenyl-1,4,6,8
      tetrahydro-6,6,8,8-tetramethyl-pyrrolo[4,5-g]-1,2,4-benzotriazin-4-yl-7-oxyl (1
      Ph), and 3-tert-butyl-1-phenyl-1,4,6,8-tetrahydro-6,6,8,8-tetraethyl-pyrrolo[4,5
      g]-1,2,4-benzotriazin-4-yl-7-oxyl (2-tBu), were synthesized and characterized by
      single-crystal X-ray analyses, variable-temperature magnetic susceptibility
      studies, and DFT calculations. Temperature dependences of the magnetic
      susceptibilities of 1-tBu, 1-Ph, and 2-tBu exhibit broad maxima at 70, 71, and 43
      K, respectively. Although these radical derivatives form a columnar or chained
      assembly in the solid state, magnetic measurements of diluted samples in the
      polymer matrices and computational results imply that the magnetic properties of
      the polycrystalline sample can be explained by a two-spin system with an
      intramolecular antiferromagnetic interaction. The magnetic behavior can be
      reproduced by using the Bleaney-Bowers model, with 2J=-80.0 cm-1 for 1-tBu, 2J=
      77.1 cm-1 for 1-Ph, and 2J=-48.9 cm-1 for 2-tBu. The moderately strong
      intramolecular antiferromagnetic interactions can be interpreted by a through
      bond interaction through the nonconjugated framework and/or through-space
      interactions based on molecular orbital theory. The strong distance dependency
      between the N-O spin site and vinylic carbon atoms indicates that the orbital
      interaction plays an important role in the intramolecular magnetic interaction.
      The reduced magnetic interaction in 2-tBu relative to those of 1-tBu and 1-Ph can
      be attributed to restricted rotation of the tetraethyl group.

PMID- 29573494
TI  - Limitations of Steric Bulk: Towards Phospha-germynes and Phospha-stannynes.
AB  - The use of bulky aryl(silyl)amides (R) as substituents for the stabilisation of
      phospha-germynes and phospha-stannynes (R-Ge=P and R-Sn=P, respectively) is
      described. Such species can be transiently generated by photolysis of the
      phosphaketene precursors (RE(PCO); E=Ge, Sn). Utilisation of bulky amides R1 and
      R2 (R1 =Ar**NSi(OtBu)3 , where Ar**=2,6-bis[bis(4-tert-butylphenyl)methyl]-4
      methylphenyl; R2 =Ar***NSi(iPr)3 , where Ar***=2,6-bis[bis(3,5-di-tert
      butylphenyl)methyl]-4-methylphenyl) facilitates the formation of diphosphene-type
      dimers, [(RGe)P]2 and [(RSn)P]2 . In an effort to circumvent dimerisation, the
      bulkier R3 substituent (R3 =Ar***NSi(4-tert-butylphenyl)3 ) was employed in an
      analogous series of experiments. This affords cyclic germylenes and stannylenes
      due to insertion of the terminal phosphide into Si-C bonds of the R3 substituent,
      which in case of the stannylene could act as a trap for another R3 -Sn=P moiety.
      All attempts to isolate terminal phosphide species were unsuccessful due to the
      reactivity of such compounds towards the organic periphery of the bulky amides,
      highlighting the limitations of highly sterically demanding functionalities.

PMID- 29573495
TI  - Efficient in planta gene targeting in Arabidopsis using egg cell-specific
      expression of the Cas9 nuclease of Staphylococcus aureus.
AB  - Gene targeting (GT), the programmed change of genomic sequences by homologous
      recombination (HR), is still a major challenge in plants. We previously developed
      an in planta GT strategy by simultaneously releasing from the genome a dsDNA
      donor molecule and creating a double-stranded break (DSB) at a specific site
      within the targeted gene. Using Cas9 form Streptococcus pyogenes (SpCas9) under
      the control of a ubiquitin gene promoter, we obtained seeds harbouring GT events,
      although at a low frequency. In the present research we tested different
      developmentally controlled promotors and different kinds of DNA lesions for their
      ability to enhance GT of the acetolactate synthase (ALS) gene of Arabidopsis. For
      this purpose, we used Staphylococcus aureus Cas9 (SaCas9) nuclease and the SpCas9
      nickase in various combinations. Thus, we analysed the effect of single-stranded
      break (SSB) activation of a targeted gene and/or the HR donor region. Moreover,
      we tested whether DSBs with 5' or 3' overhangs can improve in planta GT.
      Interestingly, the use of the SaCas9 nuclease controlled by an egg cell-specific
      promoter was the most efficient: depending on the line, in the very best case 6%
      of all seeds carried GT events. In a third of all lines, the targeting occurred
      around the 1% range of the tested seeds. Molecular analysis revealed that in
      about half of the cases perfect HR of both DSB ends occurred. Thus, using the
      improved technology, it should now be feasible to introduce any directed change
      into the Arabidopsis genome at will.

PMID- 29573496
TI  - Molecular diversity and landscape genomics of the crop wild relative Triticum
      urartu across the Fertile Crescent.
AB  - Modern plant breeding can benefit from the allelic variation that exists in
      natural populations of crop wild relatives that evolved under natural selection
      in varying pedoclimatic conditions. In this study, next-generation sequencing was
      used to generate 1.3 million genome-wide single nucleotide polymorphisms (SNPs)
      on ex situ collections of Triticum urartu L., the wild donor of the Au subgenome
      of modern wheat. A set of 75 511 high-quality SNPs were retained to describe 298
      T. urartu accessions collected throughout the Fertile Crescent. Triticum urartu
      showed a complex pattern of genetic diversity, with two main genetic groups
      distributed sequentially from west to east. The incorporation of geographical
      information on sampling points showed that genetic diversity was correlated to
      the geographical distance (R2  = 0.19) separating samples from Jordan and
      Lebanon, from Syria and southern Turkey, and from eastern Turkey, Iran and Iraq.
      The wild emmer genome was used to derive the physical positions of SNPs on the
      seven chromosomes of the Au subgenome, allowing us to describe a relatively slow
      decay of linkage disequilibrium in the collection. Outlier loci were described on
      the basis of the geographic distribution of the T. urartu accessions, identifying
      a hotspot of directional selection on chromosome 4A. Bioclimatic variation was
      derived from grid data and related to allelic variation using a genome-wide
      association approach, identifying several marker-environment associations (MEAs).
      Fifty-seven MEAs were associated with altitude and temperature measures while 358
      were associated with rainfall measures. The most significant MEAs and outlier
      loci were used to identify genomic loci with adaptive potential (some already
      reported in wheat), including dormancy and frost resistance loci. We advocate the
      application of genomics and landscape genomics on ex situ collections of crop
      wild relatives to efficiently identify promising alleles and genetic materials
      for incorporation into modern crop breeding.

PMID- 29573497
TI  - Inverse association for diagnosis of Alzheimer's disease subsequent to both
      melanoma and non-melanoma skin cancers in a large, urban, single-centre,
      Midwestern US patient population.
AB  - BACKGROUND: Although literature demonstrates a decreased risk of Alzheimer's
      disease (AD) in individuals with various cancers, including squamous cell cancers
      (SCC) and basal cell cancers (BCC) comprising non-melanoma skin cancers (NMSC),
      there is a paucity of literature to substantiate an association between malignant
      melanoma (MM) and AD. OBJECTIVE: The aim of this study was to determine whether
      an association exists between MM and AD as well as for NMSC and AD. METHODS: A
      large urban, Midwestern, US, single-centre, medical record (EMR) data repository
      was searched between January 2001 and December 2015, to identify all patients at
      age >=60 and <89 years with a clinic follow-up of at least 1 year and no
      diagnosis for AD, MM or NMSC at the time of the study entry. Data collected
      included age, gender, race and duration of follow-up. MM and NMSC were detected
      by ICD-9 codes and ICD-10 codes. Incident diagnosis of AD was also detected by
      ICD-9 and ICD-10 codes. Logistic regression analysis was utilized to obtain crude
      and adjusted odds ratios (ORs). RESULTS: Data for a total of 82 925 patients with
      known race and gender and were detected. After adjusting for confounding factors
      (race, gender, age, cerebrovascular disease, peripheral vascular disease and
      diabetes), there was a significant decreased risk of subsequent AD in patients
      with MM (OR: 0.39; 95% CI: 0.16-0.96; P = 0.042) as well as in patients with BCC
      (OR: 0.18; 95% CI: 0.08-0.45; P < 0.0001) and for patients with SCC (OR: 0.08;
      95% CI: 0.01-0.56; P = 0.013). CONCLUSION: These findings add to the growing body
      of evidence for a decreased risk of AD in patients with various cancers and
      highlight the need for ongoing research to elucidate both neurologic and biologic
      mechanisms that may underlie this apparent inverse association.

PMID- 29573498
TI  - Correlation between fetoplacental Dopplers and cardiac function in term fetuses.
AB  - OBJECTIVE: Redistribution of cardiac output is responsible for the "brain
      sparing" effect seen during periods of fetal stress. Our aim was to prospectively
      investigate the correlation between feto-placental Dopplers and cardiac function.
      METHODS: This prospective, observational study included normotensive women with
      appropriately grown, non-anomalous, singleton pregnancies. Participants underwent
      fortnightly ultrasounds from 36 weeks' gestation and intrapartum and neonatal
      outcomes were recorded. The correlation between fetoplacental Dopplers and
      various indices of cardiac function were evaluated.  RESULTS: The final cohort
      included 273 women. The left ventricular cardiac output (LVCO), left to right
      ventricular cardiac output ratio (LVCO/RVCO) and global left ventricular strain
      were positively correlated with the cerebro-placental ratio (CPR) (p<0.001 and
      rho=0.29), (p<0.001, r=0.41) and (p<0.01 and rho=0.17) respectively. The CPR was
      inversely correlated with the left ventricular myocardial performance index
      (LVMPI) (p<0.01, rho=-0.18) and the RVCO, (p<0.001, rho=-0.28). The LVCO and
      global left ventricular strain were positively correlated with umbilical venous
      flow (p=0.04 and rho=0.18) and (p<0.001 and rho=0.25) respectively. There was no
      or minimal correlation between either the mean Uterine artery PulsatiIity Index
      or Umbilical artery PulsatiIity Index with any cardiac indices. CONCLUSION: The
      fetal CPR, middle cerebral artery pulsatility index and umbilical venous flow are
      positively correlated with LVCO, LVCO/RVCO and global left ventricular strain in
      term low risk women.

PMID- 29573499
TI  - Misorientation-Angle-Dependent Phase Transformation in van der Waals Multilayers
      via Electron-Beam Irradiation.
AB  - Misorientation-angle dependence on layer thickness is an intriguing feature of
      van der Waals materials, which causes stark optical gain and electrical transport
      modulation. However, the influence of misorientation angle on phase
      transformation is not determined yet. Herein, this phenomenon in a MoS2
      multilayer via in situ electron-beam irradiation is reported. An AA'-stacked MoS2
      bilayer undergoes structural transformation from the 2H semiconducting phase to
      the 1T' metallic phase, similar to a MoS2 monolayer, which is confirmed via in
      situ transmission electron microscopy. Moreover, non-AA' stacking, which has no
      local AA' stacking order in the Moire pattern, does not reveal such a phase
      transformation. While a collective sliding motion of chalcogen atoms easily
      occurs during the transformation in AA' stacking, in non-AA' stacking it is
      suppressed by the weak van der Waals strength and by the chalcogen atoms
      interlocked at different orientations, which disfavor their kinetics by the
      increased entropy of mixing.

PMID- 29573501
TI  - First-trimester and combined first- and second-trimester prediction of small-for
      gestational age and late fetal growth restriction.
AB  - OBJECTIVE: To develop a first-trimester or combined first- and second-trimester
      screening algorithm for the prediction of small-for-gestational age (SGA) and
      late fetal growth restriction (FGR). METHODS: This was a retrospective study of
      women with singleton pregnancy, who underwent routine first-, second- and third
      trimester ultrasound assessment. Late FGR was defined, at >= 32 weeks' gestation
      in the absence of congenital anomalies, as either (i) estimated fetal weight
      (EFW) or birth weight (BW) < 3rd centile, or (ii) EFW < 10th centile and either
      uterine artery mean pulsatility index (UtA-PI) > 95th centile or cerebroplacental
      ratio (CPR) < 5th centile. Neonates with BW < 10th centile, regardless of
      prenatal parameters, were defined as SGA. The predictive effectiveness of
      maternal and first- and second-trimester factors was tested using logistic
      regression and receiver-operating characteristics curve analyses. RESULTS: A
      total of 3520 fetuses were included (late FGR, n = 109 (3.1%); SGA, n = 292
      (8.3%)). Of the late FGR cases, 56 (1.6%) fulfilled the antenatal criteria (EFW <
      3rd centile or EFW < 10th centile plus abnormal UtA-PI or CPR) and were defined
      as prenatally detected late FGR. A first-trimester screening model (comprising
      conception method, smoking status, maternal height, pregnancy-associated plasma
      protein-A (PAPP-A) and UtA-PI) could predict 50.0% of the prenatally diagnosed
      and 36.7% of the overall late FGR fetuses for a 10% false-positive rate (FPR). A
      model combining first- and second-trimester screening parameters (conception
      method, smoking status, PAPP-A, second- trimester EFW, head
      circumference/abdominal circumference ratio and UtA-PI) could predict 78.6% of
      the prenatally detected, and 59.6% of the overall late FGR fetuses, for a 10% FPR
      (area under the curve 0.901 (95% CI, 0.856-0.947) and 0.855 (95% CI, 0.818
      0.891), respectively). The prediction of SGA was suboptimal for both first
      trimester and combined screening. CONCLUSIONS: A simple model combining maternal
      and first- and second-trimester predictors can detect 60% of fetuses that will
      develop late FGR, and 79% of those fetuses that will be classified prenatally as
      late FGR, for a 10% FPR. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 29573500
TI  - Effectiveness of palliative care interventions offering social support to people
      with life-limiting illness-A systematic review.
AB  - Individuals managing the challenges of life-limiting illness require adequate
      social support to maintain quality of life. Qualitative research reports that
      patients value highly the social support obtained in palliative care
      interventions such as day care and group therapies. This systematic review aims
      to summarise existing quantitative evidence on palliative care interventions that
      facilitate social support. Research literature was systematically searched using
      electronic databases and key journals. Searches returned a total of 6,247 unique
      titles of which sixteen were eligible for inclusion. Interventions include group
      therapies, group practical interventions and palliative day care. Outcome
      measures and study designs were heterogeneous. Only one study used a validated
      outcome measure of social support. Benefits were influenced by participant
      characteristics such as baseline distress. Partial economic evaluation was
      attempted by two studies. Methodological challenges include attrition and use of
      outcome measures that were insensitive to change. Statistically significant
      results were reported in psychological and physical domains. Evidence is limited
      due to methodological issues and a scarcity of quantitative research,
      particularly regarding long-term benefits and cost-effectiveness. Interventions
      may be more beneficial to some groups than others.

PMID- 29573502
TI  - Strengths promoting the recovery process in older adults with depression.
AB  - AIMS AND OBJECTIVES: To clarify strengths for promoting the recovery process
      among older adults with depression in Japan. BACKGROUND: With the ageing of the
      global population, care and treatment of older adults with depression has been
      attracting increased attention around the world. It has become clear that the
      inner strength is inversely related to depression in older adults and that the
      use of inner strength is becoming a key concept in the context of caring for
      older adults with depression. DESIGN: Qualitative descriptive design. METHODS:
      Participant observation and narrative interviews were conducted individually with
      12 older adults with depression in care-based and daily life settings. The data
      obtained were subjected to thematic analysis using the narrative method to
      extract themes and subthemes. RESULTS: A total of three themes and 12 subthemes
      were elucidated. Strengths found to promote the recovery process in older adults
      with depression were (i) a sense of emotional connection, (ii) dialogue with life
      and (iii) discovery. CONCLUSIONS: Strengths promoting the recovery process from a
      whole-person perspective were clarified by conceptualising the experiences of
      older adults with depression with a strength orientation. A sense of emotional
      connection constituted a basis for promoting the recovery process. Dialogue with
      life and discovery were thought to represent the wisdom and spirituality found in
      the experience of old age and depression. RELEVANCE TO CLINICAL PRACTICE: While
      regarding the results of this study as basic knowledge, focusing on subjects'
      individual narratives of illness and recovery will open the possibility of a
      strength-oriented nursing practice for older adults with depression and lead to
      the provision of care that promotes recovery.

PMID- 29573503
TI  - Niche similarities among introduced and native mountain ungulates.
AB  - The niche concept provides a strong foundation for theoretical and applied
      research among a broad range of disciplines. When two ecologically similar
      species are sympatric, theory predicts they will occupy distinct ecological
      niches to reduce competition. Capitalizing on the increasing availability of
      spatial data, we built from single species habitat suitability models to a
      multispecies evaluation of the niche partitioning hypothesis with sympatric
      mountain ungulates: native bighorn sheep (BHS; Ovis canadensis) and introduced
      mountain goats (MTG; Oreamnos americanus) in the northeast Greater Yellowstone
      Area. We characterized seasonal niches using two-stage resource selection
      functions with a used-available design and descriptive summaries of the niche
      attributes associated with used GPS locations. We evaluated seasonal similarity
      in niche space according to confidence interval overlap of model coefficients and
      similarity in geographic space by comparing model predicted values with
      Schoener's D metric. Our sample contained 37,962 summer locations from 53
      individuals (BHS = 31, MTG = 22), and 79,984 winter locations from 57 individuals
      (BHS = 35, MTG = 22). Slope was the most influential niche component for both
      species and seasons, and showed the strongest evidence of niche partitioning.
      Bighorn sheep occurred on steeper slopes than mountain goats in summer and
      mountain goats occurred on steeper slopes in winter. The pattern of differential
      selection among species was less prevalent for the remaining covariates,
      indicating similarity in niche space. Model predictions in geographic space
      showed broad seasonal similarity (summer D = 0.88, winter D = 0.87), as did niche
      characterizations from used GPS locations. The striking similarities in seasonal
      niches suggest that introduced mountain goats will continue to increase their
      spatial overlap with native bighorn. Our results suggest that reducing densities
      of mountain goats in hunted areas where they are sympatric with bighorn sheep and
      impeding their expansion may reduce the possibility of competition and disease
      transfer. Additional studies that specifically investigate partitioning at finer
      scales and along dietary or temporal niche axes will help to inform an adaptive
      management approach.

PMID- 29573504
TI  - Tree mycorrhizal type predicts within-site variability in the storage and
      distribution of soil organic matter.
AB  - Forest soils store large amounts of carbon (C) and nitrogen (N), yet how
      predicted shifts in forest composition will impact long-term C and N persistence
      remains poorly understood. A recent hypothesis predicts that soils under trees
      associated with arbuscular mycorrhizas (AM) store less C than soils dominated by
      trees associated with ectomycorrhizas (ECM), due to slower decomposition in ECM
      dominated forests. However, an incipient hypothesis predicts that systems with
      rapid decomposition-e.g. most AM-dominated forests-enhance soil organic matter
      (SOM) stabilization by accelerating the production of microbial residues. To
      address these contrasting predictions, we quantified soil C and N to 1 m depth
      across gradients of ECM-dominance in three temperate forests. By focusing on
      sites where AM- and ECM-plants co-occur, our analysis controls for climatic
      factors that covary with mycorrhizal dominance across broad scales. We found that
      while ECM stands contain more SOM in topsoil, AM stands contain more SOM when
      subsoil to 1 m depth is included. Biomarkers and soil fractionations reveal that
      these patterns are driven by an accumulation of microbial residues in AM
      dominated soils. Collectively, our results support emerging theory on SOM
      formation, demonstrate the importance of subsurface soils in mediating plant
      effects on soil C and N, and indicate that shifts in the mycorrhizal composition
      of temperate forests may alter the stabilization of SOM.

PMID- 29573505
TI  - Effect of Alkaline Peroxides on the Surface of Cobalt Chrome Alloy: An In Vitro
      Study.
AB  - PURPOSE: Removable denture hygiene care is very important for the longevity of
      the rehabilitation treatment; however, it is necessary to analyze the effects
      that denture cleansers can cause on the surfaces of prostheses. Thus, this study
      evaluated the effect of alkaline peroxide-effervescent tablets on the surface of
      cobalt-chromium alloys (Co-Cr) used in removable partial dentures. MATERIALS AND
      METHODS: Circular metallic specimens (12 * 3 mm) were fabricated and were
      immersed (n = 16) in: control, Polident 3 Minute (P3M), Steradent (S), Efferdent
      (E), Polident for Partials (PFP), and Corega Tabs (CT). The surface roughness
      (MUm) (n = 10) was measured before and after periods of cleanser immersion
      corresponding to 0.5, 1, 2, 3, 4, and 5 years. Ion release was analyzed (n = 5)
      for Co, Cr, and molybdenum (Mo). Scanning electron microscopy (SEM) analysis and
      an Energy-dispersive X-ray spectroscopy (EDS) were conducted in one specimen. The
      surface roughness data were statistically analyzed (alpha = 0.05) with the
      Kruskal-Wallis test to compare the solutions, and the Friedman test compared the
      immersion durations. Ion release analysis was performed using 2-way ANOVA and
      Tukey's test. RESULTS: There was no significant surface roughness difference when
      comparing the solutions (p > 0.05) and the immersion durations (p = 0.137).
      Regarding ion release (MUg/L), CT, E, and control produced a greater release of
      Co ions than S (p < 0.05). CT produced a greater release of Cr ions than control,
      S, and P3M (p < 0.05). Finally, E caused the greatest release of Mo ions (p <
      0.05). SEM confirmed that the solutions did not damage the surfaces and EDS
      confirmed that there were no signs of oxidation. CONCLUSION: The various
      solutions tested did not have any deleterious effects on the Co-Cr alloy surface.
      Steradent, however, presented the smallest ionic release.

PMID- 29573507
TI  - Chromosome microarray analysis: A soothing guide.

PMID- 29573506
TI  - Analysis of current perioperative management with Haemate(r) P/Humate P(r) in von
      Willebrand disease: Identifying the need for personalized treatment.
AB  - INTRODUCTION: Patients with Von Willebrand disease (VWD) are regularly treated
      with VWF-containing concentrates in case of acute bleeding, trauma and dental or
      surgical procedures. AIM: In this multicentre retrospective study, current
      perioperative management with a von Willebrand factor (VWF)/Factor VIII (FVIII)
      concentrate (Haemate(r) P) in patients with VWD was evaluated. PATIENTS/METHODS:
      Patients with VWD undergoing minor or major surgery between 2000 and 2015,
      requiring treatment with a VWF/FVIII concentrate (Haemate(r) P), were included.
      Achieved VWF activity (VWF:Act) and FVIII during FVIII-based treatment regimens
      were compared to predefined target levels in national guidelines. RESULTS: In
      total, 103 patients with VWD (148 surgeries) were included: 54 type 1 (73
      surgeries), 43 type 2 (67 surgeries) and 6 type 3 (8 surgeries). Overall,
      treatment resulted in high VWF:Act and FVIII levels, defined as >=0.20 IU/mL
      above predefined levels. In patients with type 1 VWD, respectively, 65% and 91%
      of trough VWF:Act and FVIII levels were higher than target levels. In patients
      with type 2 and type 3 VWD, respectively, 53% and 57% of trough VWF:Act and 72%
      and 73% of trough FVIII levels were higher than target level. Furthermore, FVIII
      accumulation over time was observed, while VWF:Act showed a declining trend,
      leading to significantly higher levels of FVIII than VWF:Act. CONCLUSION: High
      VWF:Act and accumulation of FVIII were observed after perioperative FVIII-based
      replacement therapy in patients with VWD, both underlining the necessity of
      personalization of dosing regimens to optimize perioperative treatment.

PMID- 29573508
TI  - Anthropogenic disturbance equalizes diversity levels in arbuscular mycorrhizal
      fungal communities.
AB  - The arbuscular mycorrhizal (AM) symbiosis is a key plant-microbe interaction in
      sustainable functioning ecosystems. Increasing anthropogenic disturbance poses a
      threat to AM fungal communities worldwide, but there is little empirical evidence
      about its potential negative consequences. In this global study, we sequenced AM
      fungal DNA in soil samples collected from pairs of natural (undisturbed) and
      anthropogenic (disturbed) plots in two ecosystem types (10 naturally wooded and
      six naturally unwooded ecosystems). We found that ecosystem type had stronger
      directional effects than anthropogenic disturbance on AM fungal alpha and beta
      diversity. However, disturbance increased alpha and beta diversity at sites where
      natural diversity was low and decreased diversity at sites where natural
      diversity was high. Cultured AM fungal taxa were more prevalent in anthropogenic
      than natural plots, probably due to their efficient colonization strategies and
      ability to recover from disturbance. We conclude that anthropogenic disturbance
      does not have a consistent directional effect on AM fungal diversity; rather,
      disturbance equalizes levels of diversity at large scales and causes changes in
      community functional structure.

PMID- 29573509
TI  - Multiple breath washout: A new and promising lung function test for patients with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a devastating
      progressive lung disease affecting the parenchyma. Nitrogen multiple-breath
      washout (N2 -MBW) is a lung function test that measures ventilation
      inhomogeneity, a biomarker of small airway disease. We assessed clinical
      properties of N2 -MBW in IPF. METHODS: In this prospective cohort pilot study, 25
      IPF patients and 25 healthy controls were assessed at baseline and 10 patients at
      median 6.2 months later. Outcomes included the lung clearance index (LCI) from N2
      -MBW, forced vital capacity (FVC) from spirometry, diffusion capacity of the
      lungs for carbon monoxide (DLCO ), bronchiectasis score from computed tomography
      scans, the Gender-Age-Physiology (GAP score for IPF) stage and death or lung
      transplantation (LTx). Study end points were feasibility, repeatability,
      discriminative capacity and correlation with disease severity and structural lung
      damage. RESULTS: All patients were able to perform N2 -MBW. LCI was repeatable
      and reproducible. Median (interquartile range (IQR)) LCI in IPF was 11.6 (10.1
      13.8) in IPF versus 7.3 (6.9-8.4) in controls (P < 0.0001). LCI correlated with
      DLCO corrected for haemoglobin (corrDLCO ; r = -0.49, P = 0.016), bronchiectasis
      score (r = 0.45, P = 0.024) and the GAP stage (r = 0.59, P = 0.002), but not with
      FVC. FVC was not related to bronchiectasis. During follow-up, six patients died
      and one received LTx. LCI correlated with the latter compound outcome: hazard
      ratio (95% CI) was 2.43 (1.26; 4.69) per one LCI SD from the patient population.
      CONCLUSION: N2 -MBW is a feasible, reliable and valid lung function test in IPF.
      LCI correlates with diffusion impairment, structural airway damage and clinical
      disease severity. LCI is a promising surveillance tool in IPF that may predict
      mortality.

PMID- 29573510
TI  - Arteriovenous shunts as venous access in children with haemophilia.
AB  - INTRODUCTION: Venous access is essential in patients with haemophilia for
      administration of factor concentrates. Peripheral venipuncture may be
      challenging, particularly in young children or during immune tolerance induction
      (ITI). Central venous access devices (CVADs) carry a significant risk for
      complications. An alternative for venous access is peripheral arteriovenous
      shunts (AVSs), but there is sparse documentation in the literature. The aim of
      this study was to document our experience with AVS over 12 years in 27 boys with
      severe haemophilia. METHODS: For AVS creation, a subcutaneous vein is connected
      end-to-side with an artery at the wrist (Cimino) or at the forearm (Gracz shunt).
      Factor concentrates were substituted as for intermediate size surgery. To prevent
      shunt occlusion, heparin (5 units/kg/h) was given during the first 3 days.
      RESULTS: Indications for AVS creation were prophylaxis start (n = 20) and ITI (n
      = 7). Age at shunt insertion was median 1.5 years (minimum 8 months; maximum 11.7
      years). Shunt maturation was achieved within a median of 3 weeks after surgery
      (1.5 weeks; 18 weeks). Age when home treatment was established was median 2.1
      years (9 months; 11.7 years). Four patients required AVS revisions due to
      stenosis, but 26 of 27 patients (96%) achieved good long-term shunt function.
      There were few other complications. CONCLUSION: Arteriovenous shunts provide a
      good alternative to CVAD and carry a lower risk of complications. AVSs allow
      earlier start of prophylaxis and home therapy with an improved quality of life
      for patients and families.

PMID- 29573511
TI  - Effects of flask configuration on biofilm growth and metabolites of intertidal
      Cyanobacteria isolated from a mangrove forest.
AB  - AIMS: A novel approach was employed to study the growth of three cyanobacterial
      strains namely Oscillatoria sp. (AP17), Leptolyngbya sp. (AP3b) and Chroococcus
      sp. (AP3U). Furthermore, their broad metabolite profile, production of pigments,
      exopolysaccharide (EPS) and antimicrobial activity were evaluated in response to
      contrasting cultivation modes: biofilm or planktonic. METHODS AND RESULTS: The
      biofilm culture mode was carried out in the patented conico-cylindrical flask
      (CCF) and the planktonic culture mode was carried out in an Erlenmeyer flask
      (EF). The amount of polysaccharide that was released and that remained
      capsular/bound was higher in CCF compared to EF cultivation. Amount of
      chlorophyll a produced by Oscillatoria (AP17) was higher in the CCF compared to
      the EF cultivation. Highest antimicrobial activities were exhibited by
      Leptolyngbya (AP3b) biofilm than other biofilms as well as planktonic biomass.
      Metabolite profiles of Cyanobacteria were revealed by various chromatographic
      techniques and showed clear differences among the two contrasting modes of
      cultivation. CONCLUSIONS: The results showed clear differences in the mode of
      growth for achieving maximum chlorophyll a, EPS and bioactive metabolite
      production of the Cyanobacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      present study augmented the information which can enhance wider exploration of
      the biofilm mode of cultivation of Cyanobacteria.

PMID- 29573512
TI  - Reduced solar-induced chlorophyll fluorescence from GOME-2 during Amazon drought
      caused by dataset artifacts.
AB  - Recently, Yang et al. () reported a decrease in solar-induced chlorophyll
      fluorescence (SIF) during 2015/2016 El Nino event albeit the increase in enhanced
      vegetation index (EVI). They interpreted the reduced SIF as a signal of reduced
      ecosystem photosynthesis. However, we argue that the reduced SIF during 2015/2016
      is caused by a decreasing trend of SIF due to sensor degradation and the
      satellite overpass time is critical for drought impact assessment.

PMID- 29573514
TI  - Grey correlations: A commentary on Chehadi et al.

PMID- 29573513
TI  - Filling the glass: Effects of a positive psychology intervention on executive
      task performance in chronic pain patients.
AB  - BACKGROUND: Chronic pain is associated with emotional problems as well as
      difficulties in cognitive functioning. Prior experimental studies have shown that
      optimism, the tendency to expect that good things happen in the future, and
      positive emotions can counteract pain-induced task performance deficits in
      healthy participants. More specifically, induced optimism was found to buffer
      against the negative effects of experimental pain on executive functioning. This
      clinical experiment examined whether this beneficial effect can be extended to a
      chronic pain population. METHODS: Patients (N = 122) were randomized to a
      positive psychology Internet-based intervention (PPI; n = 74) or a waiting list
      control condition (WLC; n = 48). The PPI consisted of positive psychology
      exercises that particularly target optimism, positive emotions and self
      compassion. RESULTS: Results demonstrated that patients in the PPI condition
      scored higher on happiness, optimism, positive future expectancies, positive
      affect, self-compassion and ability to live a desired life despite pain, and
      scored lower on pain catastrophizing, depression and anxiety compared to patients
      in the WLC condition. However, executive task performance did not improve
      following completion of the PPI, compared to the WLC condition. CONCLUSIONS:
      Despite the lack of evidence that positive emotions and optimism can improve
      executive task performance in chronic pain patients, this study did convincingly
      demonstrate that it is possible to increase positive emotions and optimism in
      chronic pain patients with an online positive psychology intervention. It is
      imperative to further explore amendable psychological factors that may reduce the
      negative impact of pain on executive functioning. SIGNIFICANCE: We demonstrated
      that an Internet-based positive psychology intervention strengthens optimism and
      positive emotions in chronic pain patients. These emotional improvements are not
      associated with improved executive task performance. As pain itself often cannot
      be relieved, it is imperative to have techniques to reduce the burden of living
      with chronic pain.

PMID- 29573515
TI  - Knowledge expectations of orthopaedic patients.
AB  - AIM: To describe and compare knowledge expectations and received knowledge in
      elective orthopaedic surgery patients. BACKGROUND: Population aging, increasing
      incidence of osteoarthritis, the growing number of surgical procedures, and
      reduced clinical stays underline the need for a new approach to patient
      education. DESIGN: This study has a descriptive, comparative design. METHODS:
      Data were collected from 263 patients who had total hip and knee replacement
      elective surgery during 3 years (2009-2012) in 5 public hospitals in Spain. The
      Knowledge Expectation of Hospital Patients and the Received Knowledge of Hospital
      Patients Scales were used to collect data. The questionnaires were filled before
      hospital admission, at discharge and at follow-up 6 to 7 months later. RESULTS:
      Surgical patients received less knowledge than they expected. Patients'
      expectations were only met in the functional dimension. At follow-up, patients
      reported that they perceived having acquired more knowledge during their hospital
      stay than they reported at the time of discharge. Knowledge expectations and
      knowledge received were related to employment status, gender, and previous
      contact experience with the hospital. CONCLUSION: Knowledge expectations were not
      met, and results showed the need to improve education for orthopaedic patients
      throughout the perioperative process, not only during hospitalization.

PMID- 29573516
TI  - Reagent substitutions in the Centers for Disease Control and Prevention Nijmegen
      Bethesda assay for factor VIII inhibitors.

PMID- 29573517
TI  - Medical Certificates of Cause of Death for people with intellectual disabilities:
      A systematic literature review.
AB  - BACKGROUND: Mortality studies can help reduce health inequalities by informing
      public policy through a better understanding of causes of death and
      comorbidities. Mortality studies often rely on Medical Certificates of Cause of
      Death (MCCD) for data. METHOD: A systematic review was undertaken to identify the
      extent and nature of issues in recording causes of death for people with
      intellectual disability on MCCD. RESULTS: Fifteen of the 25 articles included in
      the literature review raised concerns about the accuracy of MCCD in identifying
      the cause(s) of death of people with intellectual disability. The most frequent
      issues were the under-reporting of intellectual disability on MCCD, and listing
      intellectual disability or an associated condition as an underlying cause of
      death. CONCLUSIONS: Concerns about the accuracy and reliability of MCCD for
      people with intellectual disability raise questions about mortality data based on
      MCCD. Clear guidance is required from WHO for those completing MCCD for people
      with intellectual disability.

PMID- 29573518
TI  - Oxygen uptake rate in alginate producer (algU+) and nonproducer (algU-) strains
      of Azotobacter vinelandii under nitrogen-fixation conditions.
AB  - AIMS: The sigma E (AlgU) in Azotobacter vinelandii has been shown to control the
      expression of cydR gene, a repressor of genes of the alternative respiratory
      chain, and alginate has been considered a barrier for oxygen diffusion.
      Therefore, the aim of the present study was to compare the respiratory activity
      of an alginate nonproducing strain, lacking the sigma factor E (algU-), and
      polymer-producing strains (algU+) of A. vinelandii under diazotrophic conditions
      at different aeration conditions. METHODS AND RESULTS: Our results reveal that
      under diazotrophic and high aeration conditions, A. vinelandii strain OP (algU-)
      had a specific oxygen consumption rate higher (30 and 54%) than those observed in
      the OP algU+-complemented strain, named OPAlgU+, and the ATCC 9046 respectively.
      However, the specific growth rate and biomass yields (based on oxygen and
      sucrose) were lower for OP cultivations as compared to the algU+ strains. These
      differences were partially explained by an increase in 1.5-fold of cydA relative
      expression in the OP strain, as compared to that obtained in the isogenic OPAlgU+
      strain. CONCLUSIONS: Overall, our results confirm the important role of algU gene
      on the regulation of respiratory metabolism under diazotrophic growth when A.
      vinelandii is exposed to high aeration. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study highlights the role of AlgU to control respiration of A. vinelandii
      when exposed to diazotrophy.

PMID- 29573519
TI  - Sagittal abdominal diameter resembles waist circumference as a surrogate marker
      of insulin resistance in adolescents-Brazilian Metabolic Syndrome Study.
AB  - OBJECTIVE: To evaluate the association of the sagittal abdominal diameter (SAD)
      with insulin resistance (IR) and metabolic syndrome (MetS) components, and to
      compare SAD with waist circumference (WC). SUBJECTS/METHODS: This was a
      multicenter, cross-sectional study of 520 adolescents (10- to 18-years old). IR
      was assessed using the homeostasis model assessment of IR (HOMA-IR) and the
      hyperglycaemic clamp (n = 76). RESULTS: SAD and WC were positively correlated
      with HOMA-IR (r = 0.637 and r = 0.653) and inversely correlated with the clamp
      derived insulin sensitivity index (ISI) (r = -0.734 and r = -0.731); P < .001. In
      the multivariable linear regression analysis, SAD was positively associated with
      HOMA-IR (B = 0.046 +/- 0.003) and inversely associated with the clamp-derived ISI
      (B = -0.084 +/- 0.009) after adjusting for sex, age, and Tanner's stages (P <
      .001). When WC replaced the SAD, it was positively associated with HOMA-IR (B =
      0.011 +/- 0.001) and inversely associated with the clamp-derived ISI (B = -0.018
      +/- 0.002); P < .001. The values of the areas under the curves (AUC) were 0.823
      and 0.813 for SAD and WC, respectively. In Bland-Altman analysis, there were
      agreement between both, SAD and WC, with the clamp-derived ISI (mean = 0.00; P >
      .05). The SAD and WC were positively associated with blood pressure,
      triglycerides, and uric acid, and inversely associated with high-density
      lipoprotein (HDL)-cholesterol after adjusting for sex, age, and Tanner's stages.
      CONCLUSION: The SAD was associated with IR and MetS components, with a good
      discriminatory power for detecting IR. When compared to WC, SAD showed equivalent
      results.

PMID- 29573520
TI  - Bronchiectasis in the Kimberley region of Western Australia.
AB  - OBJECTIVE: To review the work-up and inpatient management of non-cystic fibrosis
      bronchiectasis exacerbations against best practice guidelines in the Kimberley, a
      remote region of Western Australia, with the ultimate goal of improving treatment
      in the region.^ DESIGN: Retrospective cohort study and audit of remote adult
      bronchiectasis hospital admissions between 2011 and 2016. SETTING: Remote
      hospital inpatients. PARTICIPANTS: Thirty-two patients and 110 hospital
      admissions were included. Patients were >=15 years old, had computed tomography
      confirmed bronchiectasis and at least one hospital admission for acute
      respiratory illness prior to January 2011. MAIN OUTCOMES MEASURED: The 5-year
      mortality and compliance to a Lung Foundation position statement on non-cystic
      fibrosis bronchiectasis which suggests investigating for an underlying cause at
      diagnosis and during exacerbations prolonged antibiotics (10-14 days) and
      prolonged hospital admissions (>=7 days) are required. RESULTS: The overall 5
      year mortality was 21.8%, with the median age at death of 37 years (interquartile
      range, 27-63). The median duration of hospital admission was shorter than the
      recommended 3 days (interquartile range, 2-5) with 11 of 100 (11%) patients
      admitted for >=7 days. The median duration of antibiotics was also shorter than
      the recommended 7 days (interquartile range, 4-10), with 31 of the 98 (32%)
      patients prescribed >=10 days and 6 of the 98 (6%) prescribed >=14 days of
      therapy. CONCLUSION: We found under-treatment and under-investigation of non
      cystic fibrosis bronchiectasis in the Kimberley region. Five-year mortality was
      high, consistent with other rural Australian Indigenous cohorts.S Following this
      audit, a strategy to improve awareness, as well as update and promote regional
      guidelines has been developed.

PMID- 29573521
TI  - Activation of the IGF1 receptor stimulates glycogen synthesis by mink uterine
      epithelial cells.
AB  - Glycogen synthesis by mink uterine epithelial cells is stimulated by estradiol
      (E2 ) during estrus, although the mechanism/s through which the steroid promotes
      glycogen accumulation are unknown. Our aim was to determine if insulin is
      required for E2 induced glycogen synthesis by an immortalized mink uterine
      epithelial cell line (GMMe). We show that the cells expressed the genes for
      glycogen metabolizing enzymes (hexokinase 1, glucose-6-phosphatase 3, glycogen
      synthase 1, and glycogen phosphorylase-muscle), receptors for insulin, insulin
      like growth factor 1 and E2 (Esr1). Interestingly, treatment of cells with E2
      alone failed to stimulate glycogen production, whereas supraphysiological
      concentrations of insulin (50 MUg/ml) only, significantly increased glycogen
      content. Moreover, insulin + E2 increased glycogen content when compared to
      insulin alone (p < 0.05), an affect that was blocked when cells were treated with
      the pure E2 receptor antagonist ICI 182,780. Glycogen synthesis in response to
      insulin was significantly inhibited when cells were pre-treated with
      picropodophyllotoxin, an IGF1R antagonist. Treatment of cells with LY294002, a
      phosphatidylinositol 3-kinase (PI3K) antagonist, blocked insulin's effects on
      glycogen production whereas treatment with U0126, an inhibitor of mitogen
      activated kinase-kinase (MEK1/2) was without effect. These findings suggest to us
      that the affects of E2 on glycogen synthesis by GMMe cells is mediated through
      Esr1 and increased responsiveness of the cells to insulin. Because
      picropodophylotoxin blocked the effects of insulin on glycogen production, and
      both insulin and IGF1 act through PI3K, it is possible that IGF1 plays a role in
      glycogen production by these cells.

PMID- 29573522
TI  - Liver kinase B1 suppresses growth of lung cancer cells through sonic hedgehog
      signaling pathway.
AB  - Lung cancer is one of life-threatening cancers in the worldwide. Liver kinase B1
      (LKB1) has been reported to be closely related to cancers; however, the
      underlying mechanism of LKB1 in lung cancer remains unclear. In our study, a LKB1
      specific shRNA was employed to down-regulate LKB1 levels and a LKB1 over
      expression plasmid was constructed to up-regulate LKB1 levels. Thereafter, growth
      of lung cancer cells was assessed by MTT assay and flow cytometry. Effects of
      LKB1 on the activation of sonic hedgehog (Shh) signaling pathway were detected by
      Western blot. Effects of LKB1 on lung cancer growth and Shh signaling pathway
      activation were also assessed in vivo. Our results showed that LKB1 inhibited
      proliferation of lung cancer cells and induced their apoptosis. Moreover, LKB1
      inhibited Shh signaling pathway activation. Our in vivo study also showed that
      LKB1 inhibited lung cancer growth in vivo and modulated Shh signaling pathway.
      Treatment with cyclopamine, a Shh signaling pathway inhibitor, reversed the
      effects of LKB1 silencing and enhanced the effects of LKB1 over-expression.
      Results of our study demonstrate that LKB1 inhibits lung cancer growth in vitro
      and in vivo through Shh signaling pathway.

PMID- 29573523
TI  - Presenting predictors and temporal trends of treatment-related outcomes in
      diabetic ketoacidosis.
AB  - OBJECTIVE: This study examines temporal trends in treatment-related outcomes
      surrounding a diabetic ketoacidosis (DKA) performance improvement intervention
      consisting of mandated intensive care unit admission and implementation of a
      standardized management pathway, and identifies physical and biochemical
      characteristics associated with outcomes in this population. METHODS: A
      retrospective cohort of 1225 children with DKA were identified in the electronic
      health record by international classification of diseases codes and a minimum pH
      less than 7.3 during hospitalization at a quaternary children's hospital between
      April, 2009 and May, 2016. Multivariable regression examined predictors and
      trends of hypoglycemia, central venous line placement, severe hyperchloremia,
      head computed tomography (CT) utilization, treated cerebral edema and hospital
      length of stay (LOS). RESULTS: The incidence of severe hyperchloremia and head CT
      utilization decreased during the study period. Among patients with severe DKA
      (presenting pH < 7.1), the intervention was associated with decreasing LOS and
      less variability in LOS. Lower pH at presentation was independently associated
      with increased risk for all outcomes except hypoglycemia, which was associated
      with higher pH. Patients treated for cerebral edema had a lower presenting mean
      systolic blood pressure z score (0.58 [95% confidence interval (CI) -0.02-1.17]
      vs 1.23 [1.13-1.33]) and a higher maximum mean systolic blood pressure (SBP) z
      score during hospitalization (3.75 [3.19-4.31] vs 2.48 [2.38-2.58]) compared to
      patients not receiving cerebral edema treatment. Blood pressure and cerebral
      edema remained significantly associated after covariate adjustment. CONCLUSION:
      Treatment-related outcomes improved over the entire study period and following a
      performance improvement intervention. The association of SBP with cerebral edema
      warrants further study.

PMID- 29573524
TI  - Recognition and Conformational Properties of an Alternative Antithrombin Binding
      Sequence Obtained by Chemoenzymatic Synthesis.
AB  - Heparin is a highly sulfated glycosaminoglycan (GAG) of natural origin used as an
      anticoagulant and antithrombotic drug. These properties are principally based on
      the binding and activation of antithrombin (AT) through the pentasaccharide
      sequence GlcNAc/NS,6S-GlcA-GlcNS,3,6S-IdoA2S-GlcNS,6S (AGA*IA). Literature data
      show that the population of the 2 S0 ring conformation of the 2-O-sulfo-alpha-l
      iduronic acid (IdoA2S) motif correlates with the affinity and activation of AT.
      It was recently demonstrated that two synthetic AGA*IA-containing hexasaccharides
      (one G unit added at the reducing end), differing in the degree of sulfation of
      the IdoA unit, show comparable affinity and ability to activate AT, despite a
      different conformation of the IdoA residue. In this paper, the binding of these
      two glycans to AT was studied by isothermal titration microcalorimetry (ITC),
      transferred (tr-) NOESY, saturation transfer difference (STD) NMR spectroscopy
      and molecular dynamics (MD) simulations. Results indicated that both the IdoA2S
      and the IdoA units assume a 2 S0 conformation when bound with AT, and so present
      a common binding epitope for the two glycans, centred on the AGA*IA sequence.

PMID- 29573525
TI  - Kurt M. Mislow (1923-2017).
AB  - Kurt M. Mislow, Hugh Stott Taylor Professor of Chemistry Emeritus at Princeton
      University, died peacefully on October 5th, 2017 at the age of 94. Through the
      use of non-numerical mathematical models to conceptualize molecular form and
      function, Mislow pioneered the development of a modern stereochemistry, with
      contributions including the chiroptical properties of biaryls, resolution of
      phosphine oxides, and the use of NMR spectroscopy for the study of stereodynamic
      processes.

PMID- 29573526
TI  - Catalytic Enantioselective 1,3-Alkyl Shift in Alkyl Aryl Ethers: Efficient
      Synthesis of Optically Active 3,3'-Diaryloxindoles.
AB  - Reported is the first organocatalytic asymmetric 1,3-alkyl shift in alkyl aryl
      ethers for the synthesis of chiral 3,3'-diaryloxindoles using a chiral Bronsted
      acid catalyst. Preliminary results showed that each enantiomer of the 3,3'
      diaryloxindole, and a racemic mixture, showed different antiproliferative
      activities against HeLa cell lines by using an MTT assay.

PMID- 29573527
TI  - Highly Stereoselective Synthesis of 1,3-Dienes through an Aryl to Vinyl 1,4
      Palladium Migration/Heck Sequence.
AB  - An efficient aryl to vinyl 1,4-palladium migration/Heck sequence was developed
      for the stereoselective synthesis of 1,3-dienes. High stereoselectivity was
      observed not only for 1,3-dienes bearing two similar aryl groups at terminal
      positions, but also for those with configurations shown to be unfavorable with
      previous methods.

PMID- 29573528
TI  - Reversible Magnetic Agglomeration: A Mechanism for Thermodynamic Control over
      Nanoparticle Size.
AB  - We present a method for the synthesis and precise size control of magnetic
      nanoparticles in a reversible magnetic agglomeration mechanism. In this approach,
      nanoparticles nucleate and grow until a critical susceptibility is reached, in
      which magnetic attraction overcomes dispersive forces, leading to agglomeration
      and precipitation. This phase change in the system arrests nanoparticle growth
      and gives true thermodynamic control over the size of nanoparticles. We then show
      that increasing the alkyl chain length of the surfactant, and hence increasing
      steric stabilization, allows nanoparticles to grow to larger sizes before
      agglomeration occurs. Therefore, simply by choosing the correct surfactant, the
      size and magnetic properties of iron nanoparticles can be tailored for a
      particular application. With the continuous addition of the precursor solution,
      we can repeat the steps of nucleation, growth, and magnetic agglomeration
      indefinitely, making the approach suitable for large scale syntheses.

PMID- 29573529
TI  - Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury
      markers.
AB  - The mechanisms by which SGLT-2 inhibitors lower albuminuria are incompletely
      understood. We assessed in a post-hoc analysis of a cross-over trial the effects
      of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG
      to albumin), tubular markers (urinary KIM-1, NGAL and LFABP) and inflammatory
      markers (urinary MCP-1 and IL-6) to provide more insight into kidney protective
      effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%-54.8%) and
      eGFR by 5.1 (2.0-8.1) mL/min/1.73m2 compared to placebo. Dapagliflozin did not
      change glomerular charge or size selectivity index compared to placebo.
      Dapagliflozin decreased urinary KIM-1 excretion by 22.6% (0.3%-39.8%; P = .05)
      and IL-6 excretion by 23.5% (1.4%-40.6%; P = .04) compared to placebo, whereas no
      changes in NGAL, LFABP and MCP-1 were observed. During dapagliflozin treatment,
      changes in albuminuria correlated with changes in eGFR (r = 0.36; P = .05) and
      KIM-1 (r = 0.39; P = .05). In conclusion, the albuminuria-lowering effect of 6
      weeks of dapagliflozin therapy may be the result of decreased intraglomerular
      pressure or reduced tubular cell injury.

PMID- 29573531
TI  - Otto Roelen Medal: C. K. Williams / State Natural Science Award: B. Z. Tang /
      Kurt Alder Lectureship: V. K. Aggarwal.

PMID- 29573530
TI  - Knee extensor strength assessed using a vertical squat and a simple geometric
      model to calculate joint torque: An evaluation of validity and clinical utility.
AB  - AIM: We propose a simple method to measure knee extensor muscle strength using a
      single-legged vertical squat. The purpose of the present study was to assess the
      validity of this method in comparison with standard methods of measurement.
      METHODS: A total of 30 healthy adults (mean age 22 years) and 28 healthy older
      individuals (mean age 69 years) participated in this study. Knee extensor torque
      at maximum knee flexion during a single-leg squat was calculated by a geometrical
      model using height, weight and measured leg forward lean angle. Its validity as a
      measurement of knee extensor strength was assessed by comparing the results with
      maximum isometric knee extensor strength measured using an isokinetic dynamometer
      and a handheld dynamometer. RESULTS: Knee extensor torques calculated by the
      squat model were highly correlated with those calculated by the isokinetic
      dynamometer (r = 0.835) and handheld dynamometer (r = 0.884); however, the
      difference between the squat model and the isokinetic dynamometer measurements,
      and between the squat model and the handheld dynamometer measurements increased
      proportionally with increasing muscle strength. CONCLUSION: The squat model is a
      convenient way to measure knee extensor muscle strength quantitatively. However,
      it might be more suitable for individuals with quadriceps muscle weakness than
      for those with strong muscles. Geriatr Gerontol Int 2018; 18: 1125-1131.

PMID- 29573532
TI  - Iridium-Catalyzed Sequential Silylation and Borylation of Heteroarenes Based on
      Regioselective C-H Bond Activation.
AB  - An iridium-catalyzed regioselective sequential silylation and borylation of
      heteroarenes was developed, which represents a rare example of unsymmetrical
      intermolecular C-H bond difunctionalization through the introduction of two
      different functionalities during a one-pot transformation. Although the substrate
      scope for the dehydrogenative silylation of heteroarenes has been limited mainly
      to electron-rich five-membered rings, the current reaction proceeds with both
      electron-rich and electron-deficient heteroarenes with the aid of heteroatom
      directing C-H bond activation. The regioselectivity of the second borylation was
      controlled by both steric factors and the electronic effect of the silyl group
      installed in the first step. In combination with the classic cross-coupling
      reaction, this method provides rapid access to multisubstituted heteroarenes.

PMID- 29573534
TI  - A [3]Rotaxane Host Selects Between Stereoisomers.
AB  - What has it got in its pockets? A new approach to the selective binding and
      reporting of stereoisomers using mechanical bonding to produce a well-defined
      three-dimensional binding pocket was recently reported by Beer and co-workers.
      The highly stereoselective binding of stereoisomers by the reported [3]rotaxane
      suggest that the use of the mechanical bond to engineer a binding pocket has
      great potential for the development of stereoselective hosts.

PMID- 29573533
TI  - Rapid decline of anti-hepatitis C virus (HCV) antibodies following early
      treatment of incident HCV infections in HIV-infected men who have sex with men.
AB  - OBJECTIVES: Following clearance of incident hepatitis C virus (HCV) infections,
      HCV antibody levels may decline, resulting in seroreversion. It is unclear to
      what extent HCV antibody level trajectories differ between patients with
      treatment-induced sustained virological response (SVR), those with spontaneous
      clearance and those with untreated replicating HCV infection. We investigated HCV
      antibody level dynamics in HIV-infected MSM with different clinical outcomes.
      METHODS: We investigated anti-HCV antibody level dynamics following an incident
      HCV infection in 67 HIV-infected men who have sex with men (MSM) with different
      clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated
      replicating infection (n = 22). Antibody levels were measured at the time of HCV
      diagnosis, and at yearly intervals for 3 years thereafter. RESULTS: At baseline,
      median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5
      sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection,
      respectively. Over 3 years of follow-up, SVR was associated with a more
      pronounced decrease in anti-HCV levels compared with spontaneous clearance and
      untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38%
      (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions
      occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with
      spontaneous clearance. A shorter delay between time of infection and treatment
      start correlated with higher rates of decline in antibody levels. Seven patients
      experienced a reinfection. CONCLUSIONS: Treatment-induced HCV clearance was
      associated with a more pronounced decline in anti-HCV antibody levels and with
      higher rates of seroreversion compared with spontaneous clearance or untreated
      replicating HCV infection among HIV-infected MSM with incident HCV infections.
      Rapid clearance of HCV RNA following early HCV treatment might impair the
      development of persistent antibody titres.

PMID- 29573535
TI  - Prevalence and risk factors of measles seronegativity in a cohort of HIV-positive
      subjects: a retrospective study.
AB  - OBJECTIVES: Measles infection is a vaccine-preventable disease currently
      resurging in Europe. HIV-infected subjects are at higher risk of complications
      following measles infection. We investigated the risk factors associated with
      being seronegative in a cohort of HIV-infected subjects. METHODS: All HIV
      infected subjects in our cohort who had a measles serological test performed
      between December 2005 and May 2017 were retrospectively identified. A measles
      immunoglobulin G (IgG) titre > 275 mIU/mL was considered protective. Risk factors
      were analysed using logistic regression. RESULTS: Measles serology was available
      in 273 of 3124 subjects in active follow-up (8.7%). The prevalence of measles
      seronegativity was 21.6% (59 of 273). In the univariate analysis, being born
      after 1970 and HIV infection by vertical transmission were both associated with a
      higher risk of measles seronegativity, while a nadir CD4 T-cell count < 200
      cells/MUL was associated with a lower risk of measles seronegativity. In the
      multivariate analysis, only being born after 1970 [odds ratio (OR) 4.9; 95%
      confidence interval (CI) 1.3-18.7] and vertical transmission (OR 7.7; 95% CI 3.3
      18.3) were significantly associated with seronegativity. Among the vertically
      infected subjects with measles-mumps-rubella (MMR) immunization documentation,
      the median number of doses of vaccine received before testing was 2 (range 1-3).
      CONCLUSIONS: HIV-infected subjects born after 1970 and vertically infected
      subjects should be screened for measles seropositivity.

PMID- 29573536
TI  - Outcome of surgery for recurrent anal cancer: results from a tertiary referral
      centre.
AB  - AIM: Chemoradiotherapy remains the first line of treatment for anal cancer with
      surgery reserved for cancer recurrence or persistence. The low incidence of anal
      cancer means that the numbers undergoing surgery is small with centralization for
      excision to regional cancer centres. We present our experience of abdominal
      perineal excision, with reconstruction of the perineal defect (APERR), within a
      tertiary centre. METHOD: Over a 15-year period, data were collected
      retrospectively from notes of patients who underwent an APERR. The aim was to
      look at disease-free and overall survival and complications associated with flap
      reconstruction. RESULTS: In the study period, 29 patients [median age = 62
      (range: 42-81; interquartile range: 54-68) years] underwent APERR. Median follow
      up was 77 (4-200) months. Thirteen patients died during follow-up; eight from
      their disease, with a median survival time of 16 (4-63) months. Five-year
      survival was 67%. Nine (31%) patients had recurrence during the follow up period;
      this was local (n = 2), regional (n = 4), distant (n = 2) or a combination (n =
      1). Sixteen (55%) patients developed 24 complications, including nine (31%) flap
      complications and 10 (34%) parastomal hernias. Flap complications were flap
      failure (n = 1) requiring direct closure, flap dehiscence (n = 2), necrosis of
      flap tip (n = 1), wound infection (n = 4) and a bulky flap (n = 1) requiring
      liposuction. CONCLUSION: APERR of anal cancer is a feasible technique with
      excellent oncological treatment and acceptable long-term complications, although
      a higher than expected rate of parastomal hernia was noted.

PMID- 29573537
TI  - Comparison of the planned one- and elective two-stent techniques in patients with
      coronary bifurcation lesions with or without acute coronary syndrome from the
      COBIS II Registry.
AB  - OBJECTIVES: To evaluate the impacts of stent techniques on long-term clinical
      outcomes after percutaneous coronary intervention (PCI) using drug-eluting stents
      (DES) for coronary bifurcation lesions in patients with or without acute coronary
      syndrome (ACS). BACKGROUND: Few studies have investigated the impacts of stent
      techniques for treating coronary bifurcation lesions in patients with and without
      ACS. METHODS: This multicenter registry enrolled 2,897 patients undergoing PCI
      with DES for coronary bifurcation lesions. We investigated the impacts of planned
      one-stent and elective two-stent techniques in patients with (n = 1,798) and
      those without (n = 1,099) ACS. Primary endpoint was the incidence of 3-year
      target-lesion failure (TLF), defined as a composite of cardiac death, spontaneous
      myocardial infarction, and target-lesion revascularization. RESULTS: The planned
      one-stent technique reduced TLF rate compared to elective two-stent technique in
      the ACS cohort (hazard ratio [HR] 0.49; 95% confidence interval [CI] 0.34-0.74; P
      = 0.001), and not in the non-ACS cohort (HR 0.61; 95% CI 0.35-1.06; P = 0.079).
      After propensity score matching, the planned one-stent technique had a
      significantly lower TLF rate (HR 0.47; 95% CI 0.29-0.74; P = 0.001) in patients
      with ACS, and it also showed a trend toward lower TLF rate with the planned one
      stent technique in patients without ACS (9.0 vs. 14.5%, HR 0.59; 95% CI 0.32
      1.14; P = 0.116). CONCLUSIONS: Planned one-stenting reduced TLF in patients with
      ACS and it also might be beneficial in those without ACS for the treatment of
      coronary bifurcation lesions.

PMID- 29573538
TI  - Patients with spondyloarthritis are equally satisfied with follow-up by
      physiotherapist and rheumatologist.
AB  - OBJECTIVE: International guidelines recommend that patients with
      spondyloarthritis (SpA) have lifelong physiotherapy, as physical activity and
      exercise are essential for optimizing health throughout the course of the
      disease. The aim of the present study was to investigate if a physiotherapy-led
      outpatient clinic specializing in SpA could provide satisfactory follow-up as an
      alternative to standard visits with a rheumatologist (RT). We hypothesized that
      satisfaction would be similar in patients followed by a physiotherapist (PT) or
      an RT. METHODS: A total of 68 patients were randomized to follow-up every fourth
      month by a PT or RT, for three visits in total. Patient satisfaction was
      evaluated using the Leeds Satisfaction Questionnaire (LSQ). Function, mobility
      and disease activity were rated using the Bath Ankylosing Spondylitis Functional
      Index (BASFI), Mobility Index (BASMI) and Ankylosing Spondylitis Disease Activity
      Score (ASDAS). RESULTS: Patients were equally satisfied with PT and RT follow-up
      at the first (p = 0.062) and last (p = 0.710) visit. At the second visit, the RT
      group was seen by a nurse, and was more satisfied than the PT group (p = 0.015).
      Function deteriorated in both the PT (p = 0.014) and RT (p = 0.007) groups.
      Mobility increased in the PT group (p = 0.020). Disease activity was not
      affected. CONCLUSIONS: Patients seem to be equally satisfied with either of the
      follow-up regimes. The PT-led follow-up did not seem to affect the patients'
      course of disease negatively. The results indicate that it would be safe to
      implement a PT-led clinic for patients with SpA in specialist health services,
      but longer-term follow-up is necessary to support the findings of this study.

PMID- 29573540
TI  - What the neighbors say.

PMID- 29573539
TI  - Electrochemical Biosensor Composed of Silver Ion-Mediated dsDNA on Au
      Encapsulated Bi2 Se3 Nanoparticles for the Detection of H2 O2 Released from
      Breast Cancer Cells.
AB  - A newly developed electrochemical biosensor composed of a topological insulator
      (TI) and metallic DNA (mDNA) is fabricated. The bismuth selenide nanoparticle
      (Bi2 Se3 NP) is synthesized and sandwiched between the gold electrode and another
      Au-deposited thin layer (Bi2 Se3 @Au). Then, eight-silver-ion mediated double
      stranded DNA (mDNA) is immobilized onto the substrate (Bi2 Se3 @Au-mDNA) for the
      further detection of hydrogen peroxide. The Bi2 Se3 NP acts as the
      electrochemical-signal booster, while unprecedentedly its encapsulation by the Au
      thin layer keeps the TI surface states protected, improves its electrochemical
      signal stability and provides an excellent platform for the subsequent covalent
      immobilization of the mDNA through Au-thiol interaction. Electrochemical results
      show that the fabricated biosensor represents much higher Ag+ redox current (~10
      times) than those electrodes prepared without Bi2 Se3 @Au. The characterization
      of the Bi2 Se3 @Au-mDNA film is confirmed by atomic force microscopy, scanning
      tunneling microscopy, and cyclic voltammetry. The proposed biosensor shows a
      dynamic range of 00.10 * 10-6 m to 27.30 * 10-6 m, very low detection limit (10 *
      10-9 m), unique current response (1.6 s), sound H2 O2 recovery in serum, and
      substantial capability to classify two breast cancer subtypes (MCF-7 and MDA-MB
      231) based on their difference in the H2 O2 generation, offering potential
      applications in the biomedicine and pharmacology fields.

PMID- 29573542
TI  - Pulmonary transit time derived from pulmonary angiography for the diagnosis of
      hepatopulmonary syndrome.
AB  - BACKGROUND & AIMS: Pulmonary transit time (PTT) is the transit time of blood from
      the right side of the heart to the left side of the heart. The aim of the present
      study was to evaluate the role of the PTT derived from pulmonary angiography in
      the diagnosis of hepatopulmonary syndrome (HPS). METHODS: From December 2014 to
      September 2015, all patients with chronic liver disease and/or portal
      hypertension undergoing a venous interventional radiologic procedure at our
      institution were eligible for inclusion in this prospective study. Pulmonary
      angiography was performed in all patients, and the PTT, which was defined as the
      time between opacification of the pulmonary trunk and the right border of the
      left atrium, was determined. RESULTS: A total of 53 patients were included, 20 of
      whom had a positive contrast-enhanced echocardiography result and an elevated
      alveolar-arterial oxygen gradient were considered to have HPS. PTT was
      significantly shorter in patients with HPS than in those without [median, 3.34
      (interquartile range, 3.01-3.67) seconds vs 4.0 (interquartile range, 3.67-4.17)
      seconds; P < .001]. The area under the receiver operating characteristic curve of
      PTT for diagnosing HPS was 0.83 (95% confidence interval, 0.70-0.92). The optimal
      cut-off value of PTT for diagnosing HPS, based on Youden's index, was 3.55
      seconds. The sensitivity, specificity and accuracy of PTT < 3.55 seconds for
      diagnosing HPS were 70%, 85% and 79% respectively. CONCLUSIONS: Pulmonary transit
      time derived from pulmonary angiography is useful for diagnosing HPS, especially
      for patients with intracardiac shunts and inadequate echocardiographic windows.

PMID- 29573541
TI  - Treatment of infrapopliteal post-PTA dissection with tack implants: 12-month
      results from the TOBA-BTK study.
AB  - OBJECTIVES: The Tack implant is designed for focal, minimal metal management of
      dissections. This study evaluated Tacks for treating postpercutaneous
      transluminal angioplasty (PTA) dissection in patients with below-the-knee (BTK)
      arterial occlusive disease. BACKGROUND: PTA is the most commonly used
      endovascular treatment for patients with occlusive disease of the BTK vessels.
      Post-PTA dissection is a significant clinical problem that results in poor
      outcomes, but currently there are limited treatment options for managing
      dissections. METHODS: This prospective, single-arm study evaluated patients with
      CLI and BTK lesions; 11.4% were Rutherford category (RC) 4 and 88.6% were RC 5.
      BTK occlusive disease was treated with standard PTA and post-PTA dissections were
      treated with Tack placement. The primary safety endpoint was a composite of major
      adverse limb events (MALE) and perioperative death (POD) at 30 days. Other
      endpoints included: device success; procedure success (vessel patency in the
      absence of MALE); freedom from clinically driven target lesion revascularization
      (CD-TLR); primary patency; and changes in RC. Data through 12 months are
      presented. RESULTS: Thirty-two of 35 (91.4%) patients had post-PTA dissection and
      successful deployment of Tacks. Procedural success was achieved in 34/35 (97.1%)
      patients with no MALEs at 30 days. The 12-month patency rate was 78.4% by vessel,
      77.4% by patient, and freedom from CD-TLR was 93.5%. Significant (P < .0001)
      improvement from baseline was observed in RC (75% of patients improved 4 or 5
      steps). CONCLUSION: Tack implant treatment of post-PTA dissection was safe and
      effective for treatment of BTK dissections and resulted in reasonable 12-month
      patency and low rates of CD-TLR.

PMID- 29573543
TI  - Engineering d-limonene synthase down-regulation in orange fruit induces
      resistance against the fungus Phyllosticta citricarpa through enhanced
      accumulation of monoterpene alcohols and activation of defence.
AB  - Terpene volatiles play an important role in the interactions between specialized
      pathogens and fruits. Citrus black spot (CBS), caused by the fungus Phyllosticta
      citricarpa, is associated with crop losses in different citrus-growing areas
      worldwide. The pathogen may infect the fruit for 20-24 weeks after petal fall,
      but the typical hard spot symptoms appear when the fruit have almost reached
      maturity, caused by fungal colonization and the induction of cell lysis around
      essential oil cavities. d-Limonene represents approximately 95% of the total oil
      gland content in mature orange fruit. Herein, we investigated whether orange
      fruit with reduced d-limonene content in peel oil glands via an antisense (AS)
      approach may affect fruit interaction with P. citricarpa relative to empty vector
      (EV) controls. AS fruit showed enhanced resistance to the fungus relative to EV
      fruit. Because of the reduced d-limonene content, an over-accumulation of
      linalool and other monoterpene alcohols was found in AS relative to EV fruit. A
      global gene expression analysis at 2 h and 8 days after inoculation with P.
      citricarpa revealed the activation of defence responses in AS fruit via the up
      regulation of different pathogenesis-related (PR) protein genes, probably as a
      result of enhanced constitutive accumulation of linalool and other alcohols. When
      assayed in vitro and in vivo, monoterpene alcohols at the concentrations present
      in AS fruit showed strong antifungal activity. We show here that terpene
      engineering in fruit peels could be a promising method for the development of new
      strategies to obtain resistance to fruit diseases.

PMID- 29573544
TI  - The State and Challenges of Anode Materials Based on Conversion Reactions for
      Sodium Storage.
AB  - Sodium-ion batteries (SIBs) have huge potential for applications in large-scale
      energy storage systems due to their low cost and abundant sources. It is
      essential to develop new electrode materials for SIBs with high performance in
      terms of energy density, cycle life, and cost. Metal binary compounds that
      operate through conversion reactions hold promise as advanced anode materials for
      sodium storage. This Review highlights the storage mechanisms and advantages of
      conversion-type anode materials and summarizes their recent development. Although
      conversion-type anode materials have high theoretical capacities and abundant
      varieties, they suffer from multiple challenging obstacles to realize commercial
      applications, such as low reversible capacity, large voltage hysteresis, low
      initial coulombic efficiency, large volume changes, and low cycling stability.
      These key challenges are analyzed in this Review, together with emerging
      strategies to overcome them, including nanostructure and surface engineering,
      electrolyte optimization, and battery configuration designs. This Review provides
      pertinent insights into the prospects and challenges for conversion-type anode
      materials, and will inspire their further study.

PMID- 29573545
TI  - Nanostructuring Lipophilic Dyes in Water Using Stable Vesicles, Quatsomes, as
      Scaffolds and Their Use as Probes for Bioimaging.
AB  - A new kind of fluorescent organic nanoparticles (FONs) is obtained using
      quatsomes (QSs), a family of nanovesicles proposed as scaffolds for the
      nanostructuration of commercial lipophilic carbocyanines (1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI), 1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indodicarbocyanine perchlorate (DiD), and 1,1'-dioctadecyl
      3,3,3',3'-tetramethyl-indotricarbocyanine iodide (DiR)) in aqueous media. The
      obtained FONs, prepared by a CO2 -based technology, show excellent colloidal- and
      photostability, outperforming other nanoformulations of the dyes, and improve the
      optical properties of the fluorophores in water. Molecular dynamics simulations
      provide an atomistic picture of the disposition of the dyes within the membrane.
      The potential of QSs for biological imaging is demonstrated by performing
      superresolution microscopy of the DiI-loaded vesicles in vitro and in cells.
      Therefore, fluorescent QSs constitute an appealing nanomaterial for bioimaging
      applications.

PMID- 29573546
TI  - Nanostructure and Microstructure Fabrication: From Desired Properties to Suitable
      Processes.
AB  - When designing a new nanostructure or microstructure, one can follow a processing
      based manufacturing pathway, in which the structure properties are defined based
      on the processing capabilities of the fabrication method at hand. Alternatively,
      a performance-based pathway can be followed, where the envisioned performance is
      first defined, and then suitable fabrication methods are sought. To support the
      latter pathway, fabrication methods are here reviewed based on the geometric and
      material complexity, resolution, total size, geometric and material diversity,
      and throughput they can achieve, independently from processing capabilities. Ten
      groups of fabrication methods are identified and compared in terms of these seven
      moderators. The highest resolution is obtained with electron beam lithography,
      with feature sizes below 5 nm. The highest geometric complexity is attained with
      vat photopolymerization. For high throughput, parallel methods, such as
      photolithography (~101 m2 h-1 ), are needed. This review offers a decision-making
      tool for identifying which method to use for fabricating a structure with
      predefined properties.

PMID- 29573547
TI  - Carbon-Nanosheet Based Large-Area Electrochemical Capacitor that is Flexible,
      Foldable, Twistable, and Stretchable.
AB  - With the growing demand for wearable electronics, developing new compatible
      energy systems is a prominent topic of research. Energy systems mounted on
      wearable electronics should exhibit high cost efficiency, mechanical robustness,
      and high electrochemical activity. Herein, all-carbon-based large-area
      nanocomposites for freely deformable electrochemical capacitors are suggested to
      address these requirements. The three-dimensionally integrated, self-supported
      nanocomposites consist of activated carbons (ACs) distributed in direct spinning
      derived carbon nanotube (DS-CNT) sheets without any additives, including
      conducting agents or binders. Owing to synergetic effects of the highly porous AC
      particles, high electron transport kinetics of CNTs, and facile ion accessibility
      resulting from acid treatment, the nanocomposites show a greatly improved
      specific capacitance of 128 F g-1 , compared to that of pristine ACs (62 F g-1 ),
      based on the total mass of the electrodes. The exceptional mechanical stability
      of the nanocomposites, which are attached on prestretched elastomer substrates,
      is confirmed; only a ~15% increase in the electrical resistance is observed under
      a tensile strain of 100%, and the initial resistance is fully recovered after
      releasing. Finally, the outstanding durability and electrochemical performance of
      the deformable all-carbon-based symmetric capacitors under various mechanical
      deformations of bending, folding, twisting, and stretching are successfully
      demonstrated.

PMID- 29573548
TI  - Pine-Needle-Like Cu-Co Skeleton Composited with Li4 Ti5 O12 Forming Core-Branch
      Arrays for High-Rate Lithium Ion Storage.
AB  - High-performance of lithium-ion batteries (LIBs) rely largely on the scrupulous
      design of nanoarchitectures and smart hybridization of bespoke active materials.
      In this work, the pine-needle-like Cu-Co skeleton is reported to support highly
      active Li4 Ti5 O12 (LTO) forming Cu-Co/LTO core-branch arrays via a united
      hydrothermal-atomic layer deposition (ALD) method. ALD-formed LTO layer is
      uniformly anchored on the pine-needle-like heterostructured Cu-Co backbone, which
      consists of branched Co nanowires (diameters in 20 nm) and Cu nanowires (250-300
      nm) core. The designed Cu-Co/LTO core-branch arrays show combined advantages of
      large porosity, high electrical conductivity, and good adhesion. Due to the
      unique positive features, the Cu-Co/LTO electrodes are demonstrated with enhanced
      electrochemical performance including excellent high-rate capacity (155 mAh g-1
      at 20 C) and noticeable long-term cycles (144 mAh g-1 at 20 C after 3000 cycles).
      Additionally, the full cell assembled with activated carbon positive electrode
      and Cu-Co/LTO negative electrode exhibits high power/energy densities (41.6 Wh kg
      1 at 7.5 kW kg-1 ). The design protocol combining binder-free characteristics and
      array configuration opens a new door for construction of advanced electrodes for
      application in high-rate electrochemical energy storage.

PMID- 29573549
TI  - Probing Adsorption Behaviors of BSA onto Chiral Surfaces of Nanoparticles.
AB  - Chiral properties of nanoscale materials are of importance as they dominate
      interactions with proteins in physiological environments; however, they have
      rarely been investigated. In this study, a systematic investigation is conducted
      for the adsorption behaviors of bovine serum albumin (BSA) onto the chiral
      surfaces of gold nanoparticles (AuNPs), involving multiple techniques and
      molecular dynamic (MD) simulation. The adsorption of BSA onto both L- and D
      chiral surfaces of AuNPs shows discernible differences involving thermodynamics,
      adsorption orientation, exposed charges, and affinity. As a powerful supplement,
      MD simulation provides a molecular-level understanding of protein adsorption onto
      nanochiral surfaces. Salt bridge interaction is proposed as a major driving force
      at protein-nanochiral interface interaction. The spatial distribution features of
      functional groups (?COO- , ?NH3+ , and ?CH3 ) of chiral molecules on the
      nanosurface play a key role in the formation and location of salt bridges, which
      determine the BSA adsorption orientation and binding strength to chiral surfaces.
      Sequentially, BSA corona coated on nanochiral surfaces affects their uptake by
      cells. The results enhance the understanding of protein corona, which are
      important for biological effects of nanochirality in living organisms.

PMID- 29573550
TI  - Relative quantification of beta-adrenergic receptor in peripheral blood cells
      using flow cytometry.
AB  - Beta-adrenergic receptors (beta-ARs) play a critical role in many diseases.
      Quantification of beta-AR density may have clinical implications in terms of
      assessing disease severity and identifying patients who could potentially benefit
      from beta-blocker therapy. Classical methods for beta-AR quantification are based
      on labor-intensive and time-consuming radioligand binding assays. Here, we report
      optimization of a flow cytometry-based method utilizing a biotinylated beta-AR
      ligand alprenolol as a probe and use of this method to quantify relative receptor
      expression in healthy controls (HC). QuantumTM MESF beads were used for
      quantification in absolute fluorescence units. The probe was chemically modified
      by adding a spacer moiety between biotin and alprenolol to stabilize receptor
      binding, thus preventing binding decay. Testing of three different standard cell
      fixation and permeabilization methods (formaldehyde fixation and saponin, Tween
      20, or Triton-X 100 permeabilization) showed that the formaldehyde/Triton-X 100
      method yielded the best results. beta-AR expression was significantly higher in
      granulocytes compared to mononuclear cells. These data show that flow cytometric
      quantification of relative beta-AR expression in circulating leukocytes is a
      suitable technology for large-scale clinical application. (c) 2018 International
      Society for Advancement of Cytometry.

PMID- 29573551
TI  - Case report of high-dose hydroxocobalamin in the treatment of vasoplegic syndrome
      during liver transplantation.
AB  - A 66-year-old man with cryptogenic cirrhosis secondary to nonalcoholic
      steatohepatitis presented for orthotopic liver transplantation. Following organ
      reperfusion, the patient developed vasoplegic syndrome, with arterial blood
      pressures of approximately 60-70/30-40 mm Hg (mean arterial pressure [MAP] <45 mm
      Hg) for >90 minutes. He required high-dose norepinephrine and vasopressin
      infusions, as well as i.v. bolus doses of norepinephrine and vasopressin to reach
      a goal MAP> 60 mm Hg. There was minimal response to a 2 mg/kg i.v. bolus of
      methylene blue. Following the administration of 5 g of i.v.hydroxocobalamin, the
      patient had a profound improvement in arterial blood pressure, with subsequent
      discontinuation of the vasopressin infusion and rapid reduction of norepinephrine
      infusion from 20 to 2 MUg/min. While there have been several reports of the
      efficacy of hydroxocobalamin for vasoplegia after cardiopulmonary bypass, there
      have been only limited cases of hydroxocobalamin used in liver transplantation,
      and none with high-dose administration. We present a case of vasoplegic syndrome
      during liver transplantation that was refractory to high-dose vasopressors and
      methylene blue but responsive to high-dose i.v. hydroxocobalamin.

PMID- 29573552
TI  - How to Evaluate the Quality of Toxicokinetic-Toxicodynamic Models in the Context
      of Environmental Risk Assessment.
AB  - Environmental risk assessment (ERA) of chemicals relies on the combination of
      exposure and effects assessment. Exposure concentrations are commonly estimated
      using mechanistic fate models, but the effects side is restricted to descriptive
      statistical treatment of toxicity data. Mechanistic effect models are gaining
      interest in a regulatory context, which has also sparked discussions on model
      quality and good modeling practice. Proposals for good modeling practice of
      effect models currently focus very much on population and community models,
      whereas effects models also exist at the individual level, falling into the
      category of toxicokinetic-toxicodynamic (TKTD) models. In contrast to the higher
      level models, TKTD models are usually completely parameterized by fitting them to
      experimental data. In fact, one of their explicit aims is to replace descriptive
      methods for data analysis. Furthermore, the construction of these models does not
      fit into an orderly modeling cycle, given that most TKTD models have been under
      continuous development for decades and are being applied by many different
      research groups, for many different purposes. These aspects have considerable
      consequences for the application of frameworks for model evaluation. For example,
      classical sensitivity analysis becomes rather meaningless when all model
      parameters are fitted to a data set. We illustrate these issues with the General
      Unified Threshold model for Survival (GUTS), relate them to the quality issues
      for currently used models in ERA, and provide recommendations for the evaluation
      of TKTD models and their analyses. Integr Environ Assess Manag 2018;14:604-614.
      (c)2018 SETAC.

PMID- 29573553
TI  - Osmotic Effects in Track-Etched Nanopores.
AB  - Asymmetrically etched ion-track membranes attract great interest for both
      fundamental and technical reasons because of a large variety of applications. So
      far, conductometric measurements during track etching provide only limited
      information about the complicated asymmetric etching process. In this paper,
      monitoring of osmotic phenomena is used to elucidate the initial phase of
      nanopore formation. It is shown that strong alkaline solutions generate a
      considerable osmotic flow of water through newborn conical pores. The interplay
      between diffusion and convection in the pore channel results in a substantially
      nonlinear alkali concentration gradient and a rapid change in the pore geometry
      after breakthrough. Similar phenomena are observed in experiments with
      cylindrical track-etched pores of 15-30 nm in radius. A theoretical description
      of the diffusion-convection processes in the pores is provided.

PMID- 29573554
TI  - Formation of Metal Nanoparticles Directly from Bulk Sources Using Ultrasound and
      Application to E-Waste Upcycling.
AB  - A method for creating nanoparticles directly from bulk metal by applying
      ultrasound to the surface in the presence of a two-part surfactant system is
      presented. Implosive collapse of cavitation bubbles near the bulk metal surface
      generates powerful microjets, leading to material ejection. This liberated
      material is captured and stabilized by a surfactant bilayer in the form of
      nanoparticles. The method is characterized in detail using gold, but is also
      demonstrated on other metals and alloys, and is generally applicable. It is shown
      that nanoparticles can be produced regardless of the bulk metal form factor, and
      the method is extended to an environmentally important problem, the reclamation
      of gold from an electronic waste stream.

PMID- 29573555
TI  - Directed Self-Assembly of Star-Block Copolymers by Topographic Nanopatterns
      through Nucleation and Growth Mechanism.
AB  - Exploring the ordering mechanism and dynamics of self-assembled block copolymer
      (BCP) thin films under confined conditions are highly essential in the
      application of BCP lithography. In this study, it is aimed to examine the self
      assembling mechanism and kinetics of silicon-containing 3-arm star-block
      copolymer composed of polystyrene (PS) and poly(dimethylsiloxane) blocks as
      nanostructured thin films with perpendicular cylinders and controlled lateral
      ordering by directed self-assembly using topographically patterned substrates.
      The ordering process of the star-block copolymer within fabricated topographic
      patterns with PS-functionalized sidewall can be carried out through the type of
      secondary (i.e., heterogeneous) nucleation for microphase separation initiated
      from the edge and/or corner of the topographic patterns, and directed to grow as
      well-ordered hexagonally packed perpendicular cylinders. The growth rate for the
      confined microphase separation is highly dependent upon the dimension and also
      the geometric texture of the preformed pattern. Fast self-assembly for ordering
      of BCP thin film can be achieved by lowering the confinement dimension and also
      increasing the concern number of the preformed pattern, providing a new strategy
      for the design of BCP lithography from the integration of top-down and bottom-up
      approaches.

PMID- 29573556
TI  - A Generic Self-Assembly Process in Microcompartments and Synthetic Protein
      Nanotubes.
AB  - Bacterial microcompartments enclose a biochemical pathway and reactive
      intermediate within a protein envelope formed by the shell proteins. Herein, the
      orientation of the propanediol-utilization (Pdu) microcompartment shell protein
      PduA in bacterial microcompartments and in synthetic nanotubes, and the
      orientation of PduB in synthetic nanotubes are revealed. When produced
      individually, PduA hexamers and PduB trimers, tessellate to form flat sheets in
      the crystal, or they can self-assemble to form synthetic protein nanotubes in
      solution. Modelling the orientation of PduA in the 20 nm nanotube so as to
      preserve the shape complementarity and key interactions seen in the crystal
      structure suggests that the concave surface of the PduA hexamer faces out. This
      orientation is confirmed experimentally in synthetic nanotubes and in the
      bacterial microcompartment produced in vivo. The PduB nanotubes described here
      have a larger diameter, 63 nm, with the concave surface of the trimer again
      facing out. The conserved concave surface out characteristic of these nano
      structures reveals a generic assembly process that causes the interface between
      adjacent subunits to bend in a common direction that optimizes shape
      complementarity and minimizes steric clashes. This understanding underpins
      engineering strategies for the biotechnological application of protein nanotubes.

PMID- 29573557
TI  - The correlation between the Childhood Health Assessment Questionnaire and disease
      activity in juvenile idiopathic arthritis.
AB  - BACKGROUND: The Childhood Health Assessment Questionnaire (CHAQ) has been adapted
      from the Stanford Health Assessment Questionnaire for assessing functional
      ability in children. The present study aimed to determine the correlation between
      CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active
      and inactive disease. METHODS: JIA patients in the Pediatric Department,
      Ramathibodi Hospital, between January 2011 and December 2013, were included in
      the study. The CHAQ disability index (DI) and disease activity variables,
      including active and limited joint count, erythrocyte sedimentation rate,
      patient's global assessment (PtGA), physician's global assessment (PGA) and 27
      joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from
      medical records for each patient over six visits. At each visit, each patient was
      classified as having either active or inactive disease. The correlations between
      CHAQ-DI and disease activity variables were analysed using Spearman's
      correlation. RESULTS: The classification of 139 JIA patients consisted of
      enthesitis-related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis
      (16.5%), rheumatoid factor (RF)-negative polyarthritis (15.1%), RF-positive
      polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient
      visits, 606 were in active disease and 206 were in inactive disease. RF-negative
      polyarthritis had the highest CHAQ-DI (0.39 +/- 0.66), while oligoarthritis had
      the lowest (0.20 +/- 0.32). There was a good correlation between CHAQ-DI and
      JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a
      poor correlation between CHAQ-DI and disease activity variables during inactive
      disease. CONCLUSIONS: CHAQ-DI had a good correlation with disease activity during
      active disease but a poor correlation during inactive disease. Therefore, CHAQ is
      only useful for assessing functional ability during active disease.

PMID- 29573558
TI  - Vascularization of the tumours affects the pharmacokinetics of bleomycin and the
      effectiveness of electrochemotherapy.
AB  - Pre-clinical and clinical data indicate differences in the responses of melanoma
      and carcinoma tumours to electrochemotherapy. The purpose of this study was to
      investigate the origin of this difference, whether it is due to the intrinsic
      difference in tumour cell susceptibility to the chemotherapeutic, or due to the
      tumour micro-environment. For this purpose, we performed a pre-clinical study in
      B16F1 melanoma and TS/A carcinoma tumours in mice, in which the antitumour
      effectiveness of electrochemotherapy with bleomycin, the intrinsic sensitivity of
      tumour cells in vitro, the pharmacokinetics of bleomycin in plasma and tumours,
      and the vascularization of tumours in vivo were evaluated. The results of the
      treatment show that carcinoma was significantly more responsive to
      electrochemotherapy than melanoma. This effect cannot be ascribed to the
      intrinsic sensitivity of these cells, as melanoma cells were more sensitive than
      carcinoma cells in vitro. The difference in responses could be ascribed to
      differences in the pharmacokinetics of bleomycin; at the time of electroporation
      in carcinomas, more bleomycin was accumulated. This effect could be due to
      differences in tumour vascularization, as carcinoma tumours had numerous well
      distributed, small blood vessels, while melanomas were less vascularized,
      exhibiting predominantly larger vessels. In conclusion, this study provides
      evidence on the importance of the tumour micro-environment, particularly the
      tumour vasculature, in the responses of the tumours to bleomycin
      electrochemotherapy. Vasculature is important for the pharmacokinetics of
      bleomycin, influencing drug accumulation and drug distribution in tumours, and
      might be used as a predictive factor for the tumour response to
      electrochemotherapy.

PMID- 29573559
TI  - Effectiveness of the national food supplementary program on children growth and
      nutritional status in Iran.
AB  - This study aimed to evaluate the effectiveness of the national food distribution
      program on the growth and nutritional status of malnourished or growth-retarded
      children in 2 provinces of Iran. A quasi-experimental design was used for the
      effectiveness evaluation. Qualitative data were gathered to explain the results.
      An intervention group consisted of 362 children aged 6-72 months who were under
      coverage of the program. These children received monthly food as foodstuff, food
      vouchers, or cash. A comparison group included 409 children aged 6-72 months who
      were selected from those covered by the Primary Health Care system. Children
      anthropometric indices were measured at the baseline and also 6 months later.
      Twelve focus group discussions were held with mothers who had at least 1 child
      under the coverage of the program. At the end of the study, the mean weight-for
      age Z scores, height-for-age Z scores, and weight-for-height Z scores increased
      compared with the baselines in both groups (p < .001). The differences between 2
      groups in weight-for-age Z scores, height-for-age Z scores, and weight-for-height
      Z scores were not significant at the end of the study (p = .62, p = .91, and p =
      .94, respectively). According to the mothers' reports, factors affected the
      program outcome, that is, children anthropometric indices were low income,
      intrahousehold food sharing, irregular distribution, quantity and quality of the
      distributed food, and insufficient training. Providing foods for the malnourished
      children living in low-income families helped to prevent a worsening of their
      nutritional status; however, it has not been effective in solving the problem,
      probably due to the weak implementation and lack of empowerment strategies.

PMID- 29573560
TI  - Combination of blood and biphasic calcium phosphate microparticles for the
      reconstruction of large bone defects in dog: A pilot study.
AB  - We previously reported that biphasic calcium phosphate (BCP) microparticles
      embedded in a blood clot induces ectopic bone formation in mice and repairs a
      critical femoral defect in rat. The present pilot study aimed to evaluate in dog
      and in two models of large defects the efficacy of this composite named "blood
      for reconstruction of bone" (BRB). We show here that BRB is a cohesive
      biomaterial easy to prepare from dog autologous blood and to mold to fill large
      bone defects. First in a model of cylindrical femoral condyle defect, the BRB was
      compared with BCP particles alone. After 8 weeks, this revealed that the amount
      of mature bone was slightly and significantly higher with BRB than with BCP
      particles. Second, in a model consisting in a 2 cm-long critical interruptive
      defect of the ulna, the BRB was compared with autologous bone. After 6 months, we
      observed that implantation of BRB can induce the complete reconstruction of the
      defect and that newly formed bone exhibits high regenerative potential.
      Comparison with the results obtained with autologous bone grafting strongly
      suggests that the BRB might be an efficient biomaterial to repair large bone
      defects, as an alternative or in addition to autologous bone. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1842-1850, 2018.

PMID- 29573561
TI  - New care home admission following hospitalisation: How do older people, families
      and professionals make decisions about discharge destination? A case study
      narrative analysis.
AB  - AIMS AND OBJECTIVES: To gain an in-depth understanding of the decision-making
      processes involved in the discharge of older people admitted to hospital from
      home and discharged to a care home, as described in the case records. BACKGROUND:
      The decision for an older person to move into a care home is significant and life
      changing. The discharge planning literature for older people highlights the
      integral role of nurses in supporting and facilitating effective discharge.
      However, little research has been undertaken to explore the experiences of those
      discharged from hospital to a care home or the processes involved in decision
      making. METHOD: A purposive sample of 10 cases was selected from a cohort of 100
      individuals admitted to hospital from home and discharged to a care home. Cases
      were selected to highlight important personal, relational and structural factors
      thought to affect the decision-making process. Narrative case studies were
      created and were thematically analysed to explore the perspectives of each
      stakeholder group and the conceptualisations of risk which influenced decision
      making. RESULTS: Care home discharge decision-making is a complex process
      involving stakeholders with a range of expertise, experience and perspectives.
      Decisions take time and considerable involvement of families and the
      multidisciplinary team. There were significant deficits in documentation which
      limit the understanding of the process and the patient's voice is often absent
      from case records. The experiences of older people, families and
      multidisciplinary team members making care home decisions in the hospital setting
      require further exploration to identify and define best practice. IMPLICATIONS
      FOR PRACTICE: Nurses have a critical role in the involvement of older people
      making discharge decisions in hospital, improved documentation of the patient's
      voice is essential. Health and social care systems must allow older people time
      to make significant decisions about their living arrangements, adapting to
      changing medical and social needs.

PMID- 29573562
TI  - Lived experiences of negative symptoms in first-episode psychosis: A qualitative
      secondary analysis.
AB  - AIM: Exploring how negative symptoms are experienced and understood by
      individuals with lived experience of psychosis has the potential to offer
      insights into the complex psychosocial processes underlying negative symptom
      presentations. The aim of the current study was to investigate lived experiences
      of negative symptoms through secondary analysis of interviews conducted with
      individuals recovering from first-episode psychosis. METHOD: Transcripts of in
      depth interviews with participants (n = 24) recruited from Early Intervention in
      Psychosis services were analysed thematically with a focus on participants'
      experiences and personal understandings of features corresponding to the negative
      symptoms construct. RESULTS: Descriptions of reductions in expression, motivation
      and sociability were common features of participants' accounts. Several
      participants described the experience of having difficulty interacting as like
      being a "zombie". Some participants experienced diminished capacity for emotion,
      thought or drive as underlying these experiences. However, participants typically
      attributed reductions in expression, motivation and sociability to medication
      side-effects, lack of confidence or active avoidance intended to protect them
      from rejection or ridicule, sometimes linked to internalized stigma. CONCLUSIONS:
      Personal accounts of experiences of reduced expression, motivation and
      sociability during first-episode psychosis highlight the personal meaningfulness
      and role of agency in these features, challenging the framing of negative
      symptoms as passive manifestations of diminished capacity.

PMID- 29573564
TI  - Multi-Anion Intercalated Layered Double Hydroxide Nanosheet-Assembled Hollow
      Nanoprisms with Improved Pseudocapacitive and Electrocatalytic Properties.
AB  - Electrochemically active hollow nanostructured materials hold great promise in
      diverse energy conversion and storage applications, however, intricate synthesis
      steps and poor control over compositions and morphologies have limited the
      realization of delicate hollow structures with advanced functional properties. In
      this study, we demonstrate a one-step wet-chemical strategy for co-engineering
      the hollow nanostructure and anion intercalation of nickel cobalt layered double
      hydroxide (NiCo-LDH) to attain highly electrochemical active energy conversion
      and storage functionalities. Self-templated pseudomorphic transformation of
      cobalt acetate hydroxide solid nanoprisms using nickel nitrate leads to the
      construction of well-defined NiCo-LDH hollow nanoprisms (HNPs) with multi-anion
      intercalation. The unique hierarchical nanosheet-assembled hollow structure and
      efficiently expanded interlayer spacing offer an increased surface area and
      exposure of active sites, reduced mass and charge transfer resistance, and
      enhanced stability of the materials. This leads to a significant improvement in
      the pseudocapacitive and electrocatalytic properties of NiCo-LDH HNP with respect
      to specific capacitance, rate and cycling performance, and OER overpotential,
      outperforming most of the recently reported NiCo-based materials. This work
      establishes the potential of manipulating sacrificial template transformation for
      the design and fabrication of novel classes of functional materials with well
      defined nanostructures for electrochemical applications and beyond.

PMID- 29573563
TI  - Quality-Quantity Control Culture Enhances Vasculogenesis and Wound Healing
      Efficacy of Human Diabetic Peripheral Blood CD34+ Cells.
AB  - Autologous endothelial progenitor cell (EPC) therapy is commonly used to
      stimulate angiogenesis in ischemic repair and wound healing. However, low total
      numbers and functional deficits of EPCs make autologous EPC therapy ineffective
      in diabetes. Currently, no known ex vivo culture techniques can expand and/or
      ameliorate the functional deficits of EPCs for clinical usage. Recently, we
      showed that a quality-quantity culture (QQc) system restores the vasculogenic and
      wound-healing efficacy of murine diabetic EPCs. To validate these results and
      elucidate the mechanism in a translational study, we evaluated the efficacy of
      this QQc system to restore the vasculogenic potential of diabetic human
      peripheral blood (PB) CD34+ cells. CD34+ cells purified from PB of diabetic and
      healthy patients were subjected to QQc. Gene expression, vascular regeneration,
      and expression of cytokines and paracrine mediators were analyzed. Pre- or post
      QQc diabetic human PB-CD34+ cells were transplanted into wounded BALB/c nude mice
      and streptozotocin-induced diabetic mice to assess functional efficacy. Post-QQc
      diabetic human PB-CD34+ cell therapy significantly accelerated wound closure, re
      epithelialization, and angiogenesis. The higher therapeutic efficacy of post-QQc
      diabetic human PB-CD34+ cells was attributed to increased differentiation ability
      of diabetic CD34+ cells, direct vasculogenesis, and enhanced expression of
      angiogenic factors and wound-healing genes. Thus, QQc can significantly enhance
      the therapeutic efficacy of human PB-CD34+ cells in diabetic wounds, overcoming
      the inherent limitation of autologous cell therapy in diabetic patients, and
      could be useful for treatment of not only wounds but also other ischemic
      diseases. Stem Cells Translational Medicine 2018;7:428-438.

PMID- 29573565
TI  - Providing culturally informed mental health services to Aboriginal youth: The
      YouthLink model in Western Australia.
AB  - AIM: Aboriginal young people are more likely to experience mental health issues
      and to access mental health services than other young Australians, yet there are
      few culturally informed mental health programs and services available. This study
      describes and documents the effectiveness of the culturally sensitive model
      within YouthLink, a state-wide mental health service program in Western Australia
      for young people aged 13 to 24 years of age. METHODS: A mixed-method design
      including a descriptive approach reporting on the YouthLink framework and an
      empirical research design where 40 Aboriginal clients completed client feedback
      monitoring measures between 2014 and 2016. RESULTS: The YouthLink culturally
      informed conceptual framework adheres to best practice principles relevant to
      work with Indigenous people, family and communities. Aboriginal young people
      indicated improvement across the treatment period as shown by within-group
      differences between the first and last session scores on feedback measures.
      Therapeutic alliance (together with lower baseline acuity and female gender) also
      contributed significantly to positive treatment outcomes. CONCLUSIONS: Through a
      strong role of Aboriginal practitioners, relationships with Aboriginal
      communities, and greater service flexibility that embraces cultural meaning and
      knowledge, YouthLink has sought to enhance its response to the needs of
      Aboriginal youth.

PMID- 29573566
TI  - Teaching paediatric transgender care.
AB  - BACKGROUND: We aimed to evaluate the effect of online modules - as stand-alone
      training - on paediatric transgender-related self-perceived knowledge, objective
      knowledge, and clinical self-efficacy of learners. We previously evaluated the
      online modules as part of a larger curriculum that included observation in a
      paediatric transgender clinic, and assessed change in self-perceived knowledge.
      METHODS: Paediatric interns, psychiatry interns, fourth-year medical students and
      nurse practitioner students were administered assessments before and after the
      completion of six online modules focused on medical and psychosocial
      considerations for transgender youth. The assessments queried learner
      demographics and transgender clinical exposure. Nine items tested transgender
      related objective knowledge. Twenty-four items asked learners to rate self
      perceived transgender-specific knowledge (1, not at all knowledgeable; 5,
      completely knowledgeable). Thirteen self-efficacy items asked learners to rate
      confidence in their ability to evaluate and counsel these youth (0, not at all
      confident; 10, completely confident). Overall and subscores were calculated for
      each domain. Wilcoxon signed-rank tests were used to compare the pre- and post
      module scores. RESULTS: Thirty-six learners were eligible to join the study and
      86% (n = 31) participated. Among the participants, 90% (n = 28) completed both
      assessments. The median number of transgender patients seen before the curriculum
      was one, and 10% had past experience in a transgender clinic. Comparing pre- and
      post-module scores, the overall objective knowledge scores increased from 22 to
      56% (p < 0.001), self-perceived knowledge scores increased from 1.8 to 3.8 (p <
      0.001) and self-efficacy scores increased from 3.5 to 7.0 (p < 0.001). [What is]
      the effect of online modules on paediatric transgender-related self-perceived
      knowledge [?] DISCUSSION: This study suggests that e-learning was an effective
      stand-alone intervention to enhance transgender-related knowledge and self
      efficacy in interdisciplinary learners.

PMID- 29573567
TI  - Comparison of continuous-flow ventricular assist device therapy with intensive
      medical therapy in fixed pulmonary hypertension secondary to advanced left heart
      failure.
AB  - AIMS: Both ventricular assist device (VAD) and pulmonary vasodilator therapy have
      been shown in uncontrolled studies to improve pulmonary hypertension secondary to
      advanced left heart failure (Group 2 PH). This study aimed to compare
      haemodynamic benefits and survival in patients with fixed Group 2 PH treated with
      continuous-flow VAD to intensive medical therapy. METHODS AND RESULTS: Ninety
      five patients listed for heart transplantation with sequential right heart
      catheters were studied, 24 patients having fixed Group 2 PH (as defined by
      cardiac index < 2.8 L/min/m2 , pulmonary capillary wedge pressure > 15 mmHg, and
      transpulmonary gradient >= 15 mmHg or pulmonary vascular resistance > 3.0 WU,
      unresponsive to vasodilator challenge). Ten patients received VAD therapy, and 14
      patients received standard heart failure therapy with or without sildenafil,
      nitrates, or endothelin receptor antagonists. At repeat right heart
      catheterization, patients treated with VAD therapy demonstrated significant
      improvement in both transpulmonary gradient (19 vs. 12 mmHg, P = 0.046) and
      pulmonary vascular resistance (6.5 vs. 2.9 WU, P = 0.003) compared with baseline,
      while those treated with medical therapy did not (20.9 vs. 20.3 mmHg and 6.5 vs.
      6.4 WU, P = NS for both). Patients who received VAD therapy were significantly
      more likely to achieve normalized transpulmonary gradient (8/10 vs. 4/14, P =
      0.013) and were more likely to be listed for orthotopic heart transplantation
      (7/10 vs. 4/14, P < 0.05). There were no significant differences between groups
      in terms of all-cause mortality. CONCLUSIONS: Continuous-flow VAD therapy more
      effectively reverses fixed Group 2 PH compared with medical therapy alone and may
      allow a higher rate of listing for orthotopic heart transplantation.

PMID- 29573568
TI  - Targeting LMW-PTP to sensitize melanoma cancer cells toward chemo- and
      radiotherapy.
AB  - Tumor resistance to apoptosis is one the main causes of anticancer treatment
      failure. Previous studies showed that LMW-PTP overexpression enhances resistance
      of cancer cells to traditional anticancer drugs. Today, the role of LMW-PTP in
      inducing resistance to apoptosis in melanoma cells remains to be elucidated.
      Experimental setting include MTT assay, Annexin V/Pi method, and colony assay to
      assess whether silencing of LMW-PTP improves the sensitivity of A375 to
      dacarbazine, 5-FU, and radiotherapy. Pharmacological targeting of LMW-PTP was
      obtained using Morin, a LMW-PTP inhibitor. The ability of Morin to improve the
      effectiveness of anticancer drugs and radiotherapy was also studied. Moreover,
      PC3 cells were used as an alternative cellular model to confirm the data obtained
      with melanoma cells. We found that LMW-PTP silencing improves the effectiveness
      of dacarbazine, 5-FU, and radiotherapy. Identical results were obtained in vivo
      when Morin was used to target LMW-PTP. We demonstrated that Morin synergizes with
      dacarbazine, improving its cytotoxic activity. However, we showed that the
      combined treatment, Morin-anticancer drug, does not affect the viability of
      noncancerous cells. Knockdown of LMW-PTP sensitizes also PC3 cells to docetaxel
      and radiotherapy. In conclusion, we showed that LMW-PTP targeting improves
      effectiveness of anticancer drugs used for treatment of melanoma. Moreover, our
      results suggest that Morin could be used as adjuvant to improve the outcome of
      patients affected by metastatic melanoma.

PMID- 29573569
TI  - Significant variations in the cervical cancer screening rate in China by
      individual-level and geographical measures of socioeconomic status: a multilevel
      model analysis of a nationally representative survey dataset.
AB  - Variations in cervical cancer screening rates in China have rarely been studied
      in depth. This study aimed to investigate cervical cancer screening rates in
      relation to both individual-level and geographical measures of socioeconomic
      status (SES). Data were obtained from women aged 21 years or older by face-to
      face interviews between August 2013 and July 2014 as part of the Chinese Chronic
      Diseases and Risk Factors Surveillance. The geographical variables were obtained
      from the 2010 Chinese population census. The cervical cancer screening rates and
      95% confidence interval (CI) were estimated and mapped. Multilevel logistic
      regression models were fitted. Overall, only 21.4% (95% CI: 19.6-23.1%) of 91,816
      women aged >=21 years reported having ever been screened for cervical cancer and
      significant geographical variations at both province and county levels were
      identified (P < 0.01). The cervical cancer screening rates were the lowest among
      the poor [13.9% (95% CI: 12.1-15.7%)], uninsured [14.4% (95% CI: 10.3-18.4%)],
      less-educated [16.0% (95% CI: 14.3-17.6%)], and agricultural employment [18.1%
      (95% CI: 15.8-20.4%)] women along with those residing in areas of low economic
      status [15.0% (95% CI: 11.8-18.2%)], of low urbanization [15.6% (95% CI: 13.4
      17.7%)], and of low education status [16.0% (95% CI: 14.0-18.1%)]. The multilevel
      analysis also indicated that women with lower individual-level measures of SES
      residing in areas with low geographical measures of SES were significantly less
      likely to receive cervical cancer screening (P < 0.0001). Despite the launch of
      an organized cancer screening program in China, cervical cancer screening rates
      remain alarmingly low and significant variations based on geographical regions
      and measures of SES still exist. It is therefore essential to adopt strategies to
      better direct limited available public resources to priority groups.

PMID- 29573571
TI  - MoS2 Quantum Dots@TiO2 Nanotube Arrays: An Extended-Spectrum-Driven Photocatalyst
      for Solar Hydrogen Evolution.
AB  - TiO2 nanotube arrays (TiO2 NTAs) decorated with molybdenum disulfide quantum dots
      (MoS2 QDs) were synthesized by a facile electrodeposition method and used as a
      composite photocatalyst. MoS2 QDs/TiO2 NTAs showed enhanced photocatalytic
      activity compared with pristine TiO2 NTAs for solar light-promoted H2 evolution
      without adding any sacrificial agents or cocatalysts. The photocatalytic activity
      was influenced by the amount of MoS2 QDs coated on TiO2 NTAs. The optimal
      composition showed excellent photocatalytic activity, achieving H2 evolution
      rates of 31.36, 5.29, and 1.67 MUmol cm-2  h-1 corresponding to ultraviolet (UV,
      lambda<420 nm), visible (Vis, lambda>=420 nm), and near-infrared (NIR,
      lambda>760) illumination, respectively. The improved photocatalytic activity was
      attributed to the decreased bandgap and the surface plasmonic properties of MoS2
      QDs/TiO2 NTAs, which promoted electron-hole pair separation and the absorption
      capacity for Vis and NIR light. This study presents a facile approach for
      fabricating MoS2 QDs/TiO2 NTA heterostructures for efficient photocatalytic H2
      evolution, which will facilitate the development of designing new photocatalysts
      for environment and energy applications.

PMID- 29573570
TI  - A rapid and reliable chromosome analysis method for products of conception using
      interphase nuclei.
AB  - BACKGROUND: Karyotype determination has a central role in the genetic workup of
      pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy
      and tetraploidy) are the cause in at least 50% of first trimester, 25% of second
      trimester, and 11% of third trimester miscarriages. There are several limitations
      with the current approaches of obtaining a karyotype using traditional
      cytogenetics, fluorescence in situ hybridization with a limited number of probes,
      and chromosomal microarray. These include culture failure, incomplete results,
      lower sensitivity, and longer reporting time. METHODS: To overcome current
      limitations, a novel molecular assay is developed with a Standard Resolution
      Interphase Chromosome Profiling probe set which is a variation of the recently
      developed High Resolution probe set. It generates a molecular karyotype that can
      detect all major changes commonly associated with pregnancy loss. Initial
      familiarization of signal patterns from the probe set was used, followed by
      validation of the method using 83 samples from miscarriages in a blind study from
      three different laboratories. Finally, the clinical utility of the method was
      tested on 291 clinical samples in two commercial reference laboratory settings on
      two different continents. RESULTS: The new molecular approach not only identified
      all the chromosome changes observed by current methods, but also significantly
      improved abnormality detection by characterizing derivative chromosomes and
      finding subtle subtelomeric rearrangements, balanced and unbalanced. All
      Robertsonian translocations were also detected. The abnormality rate was 54% on
      clinical samples from commercial laboratory 1 and 63% from laboratory 2.
      CONCLUSION: The attributes of this method make it an ideal choice for the genetic
      workup of miscarriages, namely (1) near 100% successful results, (2) greater
      sensitivity than conventional chromosome analysis or FISH panels, (3) rapid
      reporting time, and (4) favorable comparisons with chromosomal microarray.

PMID- 29573572
TI  - General practice tasters for foundation doctors.
AB  - BACKGROUND: General practice (GP) is currently not viewed positively as a career
      choice, compared with other specialties, with GP training programmes struggling
      to fill posts. Opportunities to change this mindset in the early years of
      training are limited. Trainees may find themselves applying for entry into GP
      specialty training just 3-4 months after completing Foundation Year 1 (FY1), yet
      there are few GP attachments during FY1 that can provide experience of primary
      care and positively inform career choice. CONTEXT: To help ameliorate the current
      crisis in GP, recruitment and retention initiatives are needed to provide
      relevant experience of GP early in medical careers so that more doctors can make
      an informed decision to choose GP as a career. INNOVATION: FY1 doctors have been
      given the opportunity to shadow final-year GP specialty trainees (GPST3) in
      clinical practice (for between 3 and 5 days). The voluntary scheme has run
      successfully since 2014. This paper describes the taster programme and its
      evaluation. The programme has been positively received by both FY1s and GPST3
      mentors. The GPST3s are enthusiastic about GP, which appeared to 'rub off' on the
      FY1s. FY1s find it helpful to have a trainee's perspective, gaining an overview
      of what to expect, including the opportunities available to them. General
      practice is currently not viewed positively as a career choice IMPLICATIONS:
      Using GPST3 trainees as mentors for FY1 doctors is educational for both groups
      and can have a positive impact on GP recruitment. The taster demonstrated how
      varied GP is, and challenged some negative perceptions of primary care. GPST3s
      gained confidence in their knowledge about GP and greater insight into
      educational roles.

PMID- 29573573
TI  - Chiral Metal-Organic Framework Hollow Nanospheres for High-Efficiency Enantiomer
      Separation.
AB  - Chiral ZIF-8 hollow nanospheres with d-histidine as part of chiral ligands
      (denoted as H-d-his-ZIF-8) were prepared for separation of (+/-)-amine acids.
      Compared to bulk d-his-ZIF-8 without a hollow cavity, the prepared H-d-his-ZIF-8
      showed 15 times higher separation capacity and higher ee values of 90.5 % for
      alanine, 95.2 % for glutamic acid and 92.6 % for lysine, respectively.

PMID- 29573574
TI  - Prognostic significance of the infiltration of CD163+ macrophages combined with
      CD66b+ neutrophils in gastric cancer.
AB  - The polarization of tumor-associated macrophages (TAMs) and tumor-associated
      neutrophils (TANs), especially from the antitumoral phenotype to the protumoral
      phenotype under certain conditions, has an important influence on the progression
      of tumors. However, the interactions and combined prognosis of these cells are
      poorly known. Here, we detected the infiltration of CD68+ TAMs, CD163+ TAMs, and
      CD66b+ TANs in the specimens from 662 patients with GC by immunohistochemistry.
      The results showed that the infiltration of each of CD163+ , CD68+ , and CD66b+
      cells in GC tissue was significantly increased and independently associated with
      GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the
      infiltration of CD163+ and CD68+ cells in GC, and multivariate Cox analysis
      confirmed the infiltration of CD163+ cells was a better predictor for prognosis
      than that of CD68+ cells. The combination of the infiltration of CD163+ and
      CD66b+ cells provided more accurate survival prediction than any individual
      marker. Patient subgroups with CD66blow CD163low (hazard ratio (HR) = 2.161; 95%
      confidence interval (CI)  = 1.266-3.688; P < 0.001), CD66bhigh CD163high (HR =
      3.575; 95% CI = 2.155-5.933; P < 0.001), and CD66blow CD163high (HR = 7.514; 95%
      CI = 4.583-12.312; P < 0.001) were gradually associated with shorter DFS when
      compared with the subgroup with CD66bhigh CD163low . The similar result was also
      for DSS among the subgroups. Moreover, the two-marker model could more
      effectively discriminate the prognosis among the patients with chemotherapy than
      that among those without chemotherapy. We concluded that CD163+ TAMs were a more
      valuable prognostic marker than CD68+ TAMs, and CD163+ TAMs combined with CD66b+
      TANs could more precisely predict the prognosis of patients with GC.

PMID- 29573575
TI  - Heart rate response and functional capacity in patients with chronic heart
      failure with preserved ejection fraction.
AB  - AIMS: The mechanisms of exercise intolerance in heart failure with preserved
      ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has
      emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR)
      response to exercise is associated to functional capacity in patients with
      symptomatic HFpEF. METHODS AND RESULTS: We prospectively studied 74 HFpEF
      patients [35.1% New York Heart Association Class III, 53% female, age (mean +/-
      standard deviation) 72.5 +/- 9.1 years, and 59.5% atrial fibrillation].
      Functional performance was assessed by peak oxygen consumption (peak VO2 ). The
      mean (standard deviation) peak VO2 was 10 +/- 2.8 mL/min/kg. The following
      chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at
      rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) 
      resting HR], and CI according to the equation developed by Keteyian et al. (CIK)
      (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at
      rest]. In a bivariate setting, peak VO2 was positively and significantly
      correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r
      = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P =
      0.055). In a multivariable linear regression analysis that included clinical,
      analytical, echocardiographic, and functional capacity covariates, the
      chronotropic parameters were positively associated with peak VO2 . We found a
      linear relationship between Delta-HR and peak VO2 (beta coefficient of 0.03; 95%
      confidence interval: 0.004-0.05; P = 0.030); conversely, the association among
      CIs and peak VO2 was exponentially shaped. CONCLUSIONS: In patients with chronic
      HFpEF, the HR response to exercise was positively associated to patient's
      functional capacity.

PMID- 29573576
TI  - Toward clinical and molecular understanding of pathogenic variants in the ZBTB18
      gene.
AB  - BACKGROUND: Patients with pathogenic variants in ZBTB18 present with Intellectual
      Disability (ID) with frequent co-occurrence of corpus callosum (CC) anomalies,
      hypotonia, microcephaly, growth problems and variable facial dysmorphologies.
      These features illustrate a key role for ZBTB18 in brain development. METHODS:
      Patients with a pathogenic variant in ZBTB18 were detected by diagnostic whole
      exome sequencing (WES) performed in our center. We reviewed the literature and
      used GeneMatcher to include other cases. YASARA and WHAT IF were used to provide
      insight into the structural effect of missense variants located in the C2H2 zinc
      finger domains of the ZBTB18 protein. RESULTS: We give a complete overview of
      pathogenic variants in ZBTB18 detected to date, showing inconsistent presence of
      clinical features, including CC anomalies. We present four new cases with a de
      novo pathogenic variant in the ZBTB18 gene, including the fourth case in which a
      de novo p.Arg464His variant was found. CONCLUSION: Homology modeling of protein
      structure points to a variable degree of impaired DNA binding caused by missense
      variants in these domains probably leading to Loss of Function (LoF). Putative
      partial LoF may present with a less distinctive phenotype than complete LoF, as
      seen in truncating variants, which presents with an extensive variability in the
      phenotypic spectrum. Our data do not support a clear genotype to phenotype
      correlation.

PMID- 29573577
TI  - Mutation profile and associated clinical features in Chinese patients with
      cytogenetically normal acute myeloid leukemia.
AB  - INTRODUCTION: Cytogenetically normal acute myeloid leukemia (CN-AML), which
      accounted for nearly half of total AML patients, is a highly heterogeneous subset
      of AML. The specific genetic profile and the ethnic features of CN-AML are worth
      to be studied. METHODS: Using deep sequencing technology, we detected the
      mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their
      clinical features. RESULTS: A total of 503 mutations of 39 genes were identified
      in 145 (95.4%) patients, with the median number of 3 mutations per case. Nine
      genes (NPM1, CEBPA, DNMT3A, GATA2, NRAS, TET2, FLT3, IDH2, and WT1) mutated in
      more than 10% patients. Function groups of myeloid transcription factors,
      activated signaling, and DNA methylation were most affected. The distribution of
      variant allele frequencies (VAF) of recurrent genes was different among
      functional groups. High mutation rates of CEBPA and GATA2 together with the low
      frequency of FLT3-ITD mutation seemed to be the distinct characteristics of
      Chinese patients. Furthermore, CEBPAbi and GATA2 were found to mutate most in M2
      subtype, while NPM1 and DNMT3A mutated more in M4 and M5. The prognostic analysis
      identified CEBPAmo mutation as an inferior factor. FLT3-ITD, TP53, DNMT3A,
      CEBPAmo, and WT1 mutations were selected as high-risk markers to identify the CN
      AML patients with poor prognosis. CONCLUSION: Our study provided the valuable
      information of ethnic genetic characteristics and the clinical relevance of
      Chinese CN-AML patients.

PMID- 29573578
TI  - Associations of sleep duration and prediabetes prevalence in a middle-aged and
      elderly Chinese population with regard to age and hypertension: The China Health
      and Retirement Longitudinal Study baseline survey.
AB  - BACKGROUND: The aim of the present study was to examine the age-specific
      associations between self-reported sleep duration and prevalent prediabetes in
      middle-aged and elderly Chinese with or without hypertension. METHODS: In all,
      2985 Chinese adults aged >=45 years from the China Health and Retirement
      Longitudinal Study (CHARLS) baseline survey were selected for analysis. Sleep
      duration was assessed by structured questionnaires and then categorized into
      three groups (<=6, 6-8, and >8 h). The prevalence of prediabetes was defined
      using fasting plasma glucose (100-125 mg/dL) and/or HbA1c (5.7%-6.4%) in
      conjunction with no previous diabetes diagnosis and no antidiabetic medication.
      Relationships between self-reported sleep duration and prevalent prediabetes were
      examined according to age (45-60 years, middle-aged; >=60 years, elderly) and
      hypertension groups using Poisson regression models to estimate prevalence ratios
      (PRs) and 95% confidence intervals (CI). RESULTS: Compared with the reference
      group of 6-8 h sleep/night, short sleep (<=6 h/night) was associated with an
      increased risk of prediabetes in the whole sample (PR 1.09, 95% CI 1.01-1.17)
      after adjusting for confounders. This association was more pronounced in elderly
      participants without hypertension (PR 1.27, 95% CI 1.07-1.51). CONCLUSION: This
      study suggests that participants with a short sleep period are at a moderately
      increased risk of prediabetes, particularly in elderly subjects without
      hypertension. Aging and hypertension may be important in the relationship between
      short sleep and impaired glucose metabolism.

PMID- 29573579
TI  - Infundibulum of the common origin of fourth lumbar arteries and median sacral
      artery.
AB  - We describe an infundibulum of a common origin of the fourth lumbar arteries and
      the median sacral artery. To the best of our knowledge there has been no such
      published case thus far and its natural course is unknown, in view of its
      novelty. Infundibular dilatations in intracranial arteries have been described to
      progress in size and potentially rupture. Therefore, we recommended follow-up
      imaging, as part of the management, to ensure stability of the infundibulum.

PMID- 29573580
TI  - Boosting ORR Catalytic Activity by Integrating Pyridine-N Dopants, a High Degree
      of Graphitization, and Hierarchical Pores into a MOF-Derived N-Doped Carbon in a
      Tandem Synthesis.
AB  - N-doped carbon materials represent promising metal-free electrocatalysts for the
      oxygen reduction reaction (ORR), the cathode reaction in fuel cells, metal-air
      batteries, and so on. A challenge for optimizing the ORR catalytic activities of
      these electrocatalysts is to tune their local structures and chemical
      compositions in a rational and controlled way that can achieve the synergistic
      function of each factor. Herein, we report a tandem synthetic strategy that
      integrates multiple contributing factors into an N-doped carbon. With an N
      containing MOF (ZIF-8) as the precursor, carbonization at higher temperatures
      leads to a higher degree of graphitization. Subsequent NH3 etching of this highly
      graphitic carbon enabled the introduction of a higher content of pyridine-N sites
      and higher porosity. By optimizing these three factors, the resultant carbon
      materials displayed ORR activity that was far superior to that of carbon derived
      from a one-step pyrolysis. The onset potential of 0.955 V versus a reversible
      hydrogen electrode (RHE) and the half-wave potential of 0.835 V versus RHE are
      among the top ranks of metal-free ORR catalysts and are comparable to commercial
      Pt/C (20 wt %) catalysts. Kinetic studies revealed lower H2 O2 yields, higher
      electron-transfer numbers, and lower Tafel slopes for these carbon materials
      compared with that derived from a one-step carbonization. These findings verify
      the effectiveness of this tandem synthetic strategy to enhance the ORR activity
      of N-doped carbon materials.

PMID- 29573581
TI  - Automatic segmentation of pigment deposits in retinal fundus images of Retinitis
      Pigmentosa.
AB  - Retinitis Pigmentosa is an eye disease that presents with a slow loss of vision
      and then evolves until blindness results. The automatic detection of the early
      signs of retinitis pigmentosa acts as a great support to ophthalmologists in the
      diagnosis and monitoring of the disease in order to slow down the degenerative
      process. A large body of literature is devoted to the analysis of Retinitis
      Pigmentosa. However, all the existing approaches work on Optical Coherence
      Tomography (OCT) data, while hardly any attempts have been made working on fundus
      images. Fundus image analysis is a suitable tool in daily practice for an early
      detection of retinal diseases and the monitoring of their progression. Moreover,
      the fundus camera represents a low-cost and easy-access diagnostic system, which
      can be employed in resource-limited regions and countries. The fundus images of a
      patient suffering from retinitis pigmentosa are characterized by an attenuation
      of the vessels, a waxy disc pallor and the presence of pigment deposits.
      Considering that several methods have been proposed for the analysis of retinal
      vessels and the optic disk, this work focuses on the automatic segmentation of
      the pigment deposits in the fundus images. The image distortions are attenuated
      by applying a local pre-processing. Next, a watershed transformation is carried
      out to produce homogeneous regions. Working on regions rather than on pixels
      makes the method very robust to the high variability of pigment deposits in terms
      of color and shape, so allowing the detection even of small pigment deposits. The
      regions undergo a feature extraction procedure, so that a region classification
      process is performed by means of an outlier detection analysis and a rule set.
      The experiments have been performed on a dataset of images of patients suffering
      from retinitis pigmentosa. Although the images present a high variability in
      terms of color and illumination, the method provides a good performance in terms
      of sensitivity, specificity, accuracy and the F-measure, whose values are 74.43,
      98.44, 97.90, 59.04, respectively.

PMID- 29573582
TI  - Deformable respiratory motion correction for hepatic rotational angiography.
AB  - Cone-beam rotational angiography enables 3D imaging of the hepatic vasculature
      and is considered beneficial for guidance of transcatheter arterial
      chemoembolization procedures. Respiratory motion during the rotational
      acquisition challenges state-of-the-art reconstruction algorithms as intra-scan
      motion leads to inconsistencies causing substantial blurring and streaking
      artifacts in uncompensated reconstructions, suggesting the need for motion
      correction. We propose an automated method for respiratory motion estimation and
      compensation based on registration of an initial 3D arterial model to vesselness
      enhanced 2D projection images. Centerline points of the arterial tree are modeled
      as B-splines over time, the control point positions of which are optimized using
      alpha-expansion moves on graph cuts. This approach naturally allows for the
      estimation of 3D rigid translations as well as non-rigid deformations. Applied to
      a pre-clinical and a clinical acquisition, the proposed methods resulted in
      notable reductions in reprojection error and increased vessel sharpness that are
      reflected in less streaking and blurring artifact compared to the uncompensated
      case, implying superior vessel contrast. As the proposed methods are generic,
      future work will investigate their applicability to related rotational
      angiography imaging protocols, such as coronary angiography.

PMID- 29573583
TI  - An application of cascaded 3D fully convolutional networks for medical image
      segmentation.
AB  - Recent advances in 3D fully convolutional networks (FCN) have made it feasible to
      produce dense voxel-wise predictions of volumetric images. In this work, we show
      that a multi-class 3D FCN trained on manually labeled CT scans of several
      anatomical structures (ranging from the large organs to thin vessels) can achieve
      competitive segmentation results, while avoiding the need for handcrafting
      features or training class-specific models. To this end, we propose a two-stage,
      coarse-to-fine approach that will first use a 3D FCN to roughly define a
      candidate region, which will then be used as input to a second 3D FCN. This
      reduces the number of voxels the second FCN has to classify to ~10% and allows it
      to focus on more detailed segmentation of the organs and vessels. We utilize
      training and validation sets consisting of 331 clinical CT images and test our
      models on a completely unseen data collection acquired at a different hospital
      that includes 150 CT scans, targeting three anatomical organs (liver, spleen, and
      pancreas). In challenging organs such as the pancreas, our cascaded approach
      improves the mean Dice score from 68.5 to 82.2%, achieving the highest reported
      average score on this dataset. We compare with a 2D FCN method on a separate
      dataset of 240 CT scans with 18 classes and achieve a significantly higher
      performance in small organs and vessels. Furthermore, we explore fine-tuning our
      models to different datasets. Our experiments illustrate the promise and
      robustness of current 3D FCN based semantic segmentation of medical images,
      achieving state-of-the-art results.1.

PMID- 29573584
TI  - Structural studies of the cell wall polysaccharide from Lactococcus lactis
      UC509.9.
AB  - Lactococcus lactis is the most widely utilised starter bacterial species in dairy
      fermentations. The L. lactis cell envelope contains polysaccharides, which, among
      other known functions, serve as bacteriophage receptors. Our previous studies
      have highlighted the structural diversity of these so-called cell wall
      polysaccharides (CWPSs) among L. lactis strains that could account for the narrow
      host range of most lactococcal bacteriophages. In the present work, we studied
      the CWPS of L. lactis strain UC509.9, an Irish dairy starter strain that is host
      to the temperate and well-characterized P335-type phage Tuc2009. The UC509.9 CWPS
      structure was analyzed by methylation, deacetylation/deamination, Smith
      degradation and 2D NMR spectroscopy. The CWPS consists of a linear backbone
      composed of a tetrasaccharide repeat unit, partially substituted with a branched
      phosphorylated oligosaccharide having a common trisaccharide and three non
      stoichiometric substitutions.

PMID- 29573585
TI  - Synthesis of bidesmosidic lupane saponins - comparison of batch and continuous
      flow methodologies.
AB  - Synthesis of lupane bidesmosides was optimized. The title compounds were obtained
      by glycosylation of 3-O- or 28-O-substituted betulin monodesmosides with Schmidt
      donors catalyzed by TMSOTf. Classical batch procedure and microreactor technique
      were used and compared in the above synthesis. Experimental results clearly
      showed that both methods are comparable, although any particular outcome strongly
      depends on the structure of the reagents. Undesired allobetulin derivatives
      formed by the Wagner-Meerwein rearrangement were usually isolated in minute
      amounts. In the case of batch reaction, shorter reaction time significantly
      decreased formation of side-products.

PMID- 29573586
TI  - Decreased interleukin-11 levels in the semen of infertile males.
AB  - The relationship between the interleukin (IL)-11 levels and semen quality of
      infertile males remains unknown. In this study, 120 semen samples from 60
      normozoospermic volunteers and 60 infertile males were examined. The semen pH of
      the normozoospermic group was not significantly different from that of the
      infertile group. The semen volume, semen density, forward movement percentage,
      activity, survival rate and normal morphology rate of the sperm of the infertile
      group were significantly lower than those of the normozoospermic group. The semen
      IL-11 levels of the infertile group were significantly lower than those of the
      normozoospermic group. In the infertile group, semen IL-11 levels were positively
      correlated with sperm motility, vitality, survival rate and normal sperm
      morphology rate and negatively correlated with IL-17 and IL-18 levels. Therefore,
      semen IL-11 levels could be used as an index of male infertility.

PMID- 29573587
TI  - The study of wood knots using acoustic nondestructive testing methods.
AB  - In the process of wood grading with the focus on detecting wood knots,
      nondestructive testing methods based on sound transmission can assist the
      traditional characterization methods to achieve a higher efficiency and better
      results. In this paper, we use two independent methods based on resonance and
      sound speed measurements to evaluate the elastic modulus of wood beams containing
      different knots. The results show that the method based on sound speed
      measurements offers a fast procedure to evaluate whether the knot is in the
      middle of the cross-section of the beam or not. In this case, both measuring
      methods are reliable in determining the knot's characteristics. In the off-center
      case, the resonance method performs better to quantify the size of the knots.

PMID- 29573588
TI  - Virtual nondestructive evaluation for anisotropic plates using Symmetry Informed
      Sequential Mapping of Anisotropic Green's function (SISMAG).
AB  - In this article, a generalized computational method to simulate virtual
      nondestructive evaluation (NDE) of anisotropic composite plates is presented. The
      ultrasonic wave fields were computed using a modified and generalized version of
      Distributed Point Source Method (DPSM), a semi-analytical mesh-free technique.
      The anisotropic Green's functions required for DPSM implementation were
      calculated using Fourier transform method and Radon transform method and
      compared. It is established that the Green's functions obtained from two
      different methods are identical. Applying generalized mathematical formulations,
      NDE of different degrees of anisotropic: transversely isotropic, orthotropic and
      monoclinic material are simulated and reported in this article. To boost the
      computational efficiency, a Symmetry Informed Sequential Mapping of Anisotropic
      Green's function (SISMAG) is introduced with DPSM and discussed in detail. To
      prove the above claims, virtual NDE experiments of anisotropic plates with normal
      and angle incidence of the ultrasonic wave are simulated using a circular
      transducer of central frequency ~1 MHz. Wave fields inside both the fluid and the
      solid media were calculated.

PMID- 29573589
TI  - Whole organism to tissue concentration ratios derived from an Australian tropical
      dataset.
AB  - Whole organism to tissue concentration ratios (CRwo-tissue) were derived for six
      wildlife groups (freshwater birds, freshwater bivalves, freshwater fishes,
      freshwater reptiles, freshwater vascular plants and terrestrial mammals). The
      wildlife groups and data represented species common to tropical northern
      Australia. Values of CRwo-tissue were derived for between 6 and 34 elements,
      depending upon wildlife group. The values were generally similar to international
      reference values. However, differences for some element-tissue combinations could
      affect radiation dose estimates for wildlife in certain environmental exposure
      situations, including uranium mining, where these data are intended to be
      applied.

PMID- 29573590
TI  - Numerical modeling of the sources and behaviors of 222Rn, 220Rn and their
      progenies in the indoor environment-A review.
AB  - 222Rn, 220Rn and their short-lived progenies are well known radioactive indoor
      pollutants, identified as the leading environmental cause of lung cancer next to
      smoking. Apart from the conventional measurement methods, numerical modeling
      methods are developed to simulate their physical and decay processes in 222Rn and
      220Rn's life cycle, estimate their levels, concentration distributions, as well
      as effects of control strategies in the indoor environment. In this article, we
      summarized the numerical models used to illustrate the physical processes of each
      source of 222Rn and 220Rn entry into the indoor environment, and the application
      of Jacobi room models and CFD (Computational Fluid Dynamic) models used to
      present the behaviors of indoor 222Rn, 220Rn and their progenies. Furthermore, we
      consider that the development of numerical modeling of 222Rn and 220Rn would have
      a bright prospect in the directions of stochastic methods based on a steady-state
      model, the fine simulation of the time-dependent model as well as the multi
      dimension model.

PMID- 29573591
TI  - Facilitation of an end-of-life care programme into practice within UK nursing
      care homes: A mixed-methods study.
AB  - BACKGROUND: The predicted demographic changes internationally have implications
      for the nature of care that older people receive and place of care as they age.
      Healthcare policy now promotes the implementation of end-of-life care
      interventions to improve care delivery within different settings. The Gold
      Standards Framework in Care Homes (GSFCH) programme is one end-of-life care
      initiative recommended by the English Department of Health. Only a small number
      of care homes that start the programme complete it, which raises questions about
      the implementation process. AIM: To identify the type, role, impact and cost of
      facilitation when implementing the GSFCH programme into nursing care home
      practice. DESIGN: A mixed-methods study. SETTING: Nursing care homes in south
      east England. PARTICIPANTS: Staff from 38 nursing care homes undertaking the
      GSFCH programme. Staff in 24 nursing care homes received high facilitation. Of
      those, 12 also received action learning. The remaining 14 nursing care homes
      received usual local facilitation of the GSFCH programme. METHODS: Study data
      were collected from staff employed within nursing care homes (home managers and
      GSFCH coordinators) and external facilitators associated with the homes. Data
      collection included interviews, surveys and facilitator activity logs. Following
      separate quantitative (descriptive statistics) and qualitative (template) data
      analysis the data sets were integrated by 'following a thread'. This paper
      reports study data in relation to facilitation. RESULTS: Three facilitation
      approaches were provided to nursing home staff when implementing the GSFCH
      programme: 'fitting it in' facilitation; 'as requested' facilitation; and 'being
      present' facilitation. 'Being present' facilitation most effectively enabled the
      completion of the programme, through to accreditation. However, it was not
      sufficient to just be present. Without mastery and commitment, from all
      participants, including the external facilitator, learning and initiation of
      change failed to occur. Implementation of the programme required an external
      facilitator who could mediate multi-layered learning at an individual,
      organisational and appreciative system level. The cost savings in the study
      outweighed the cost of providing a 'being present' approach to facilitation.
      CONCLUSIONS: Different types of facilitation are offered to support the
      implementation of end-of-life care initiatives. However, in this study 'being
      present' facilitation, when supported by multi-layered learning, was the only
      approach that initiated the change required.

PMID- 29573592
TI  - How older adults and their informal carers prevent falls: An integrative review
      of the literature.
AB  - : Falls in older persons are prevalent and costly for the individual and the
      health system. Falls prevention guidelines have been developed from best evidence
      to minimise falls in older persons. AIM: To synthesise the literature on falls
      prevention strategies used by community dwelling older persons and/or their
      informal carers and to compare the commonly adopted strategies with those
      recommended by falls prevention guidelines. DATA SOURCES: Health sciences
      databases for full text articles published in English plus reference list
      searching of included articles. REVIEW METHOD: An integrative review approach.
      Studies were included if they identified fall prevention management strategies
      used by community dwelling older adults and/or their informal carers. Quality
      appraisal was undertaken using appropriate Joanna Briggs Institute critical
      appraisal tools. Information relevant to the aim of the review were extracted and
      coded into categories then inductively sorted into sub-themes and themes.
      RESULTS: Of the seventeen studies included in the review, eleven identified older
      adults' falls prevention strategies, two investigated fall prevention strategies
      used by carers, and four explored perspectives of older persons together with
      their carers, representing the perspectives of an estimated 501 older persons and
      102 carers. Strategies used by older adults arose because of self-awareness about
      their changing physical ability, and advice and support mainly from family or
      friends. Carer fall prevention strategy was predominantly around protection of
      the older adult from falling by discouraging independence. CONCLUSIONS: The fall
      self-management strategies adopted by older adults and their carers to prevent
      falls, in the main, do not align with international best practice fall prevention
      guidelines.

PMID- 29573593
TI  - The evidence base for psychological interventions for rheumatoid arthritis: A
      systematic review of reviews.
AB  - BACKGROUND: Psychological interventions are an important but often overlooked
      adjunctive treatment option for patients with rheumatoid arthritis. Findings from
      systematic reviews of psychological interventions for this patient group are
      conflicting. A systematic review of reviews can explain inconsistencies between
      studies and provide a clearer understanding of the effects of interventions.
      OBJECTIVES: To: 1) determine the effectiveness of psychological interventions in
      improving biopsychosocial outcomes for adults with rheumatoid arthritis, 2)
      determine the relationship between the intensity of the psychological
      interventions (number of sessions, duration of sessions, duration of
      intervention) on outcomes, and 3) assess the impact of comparator group (usual
      care, education only) on outcomes. DESIGN: We conducted a systematic review of
      reviews using the following inclusion criteria: 1) randomised controlled trials
      of psychological interventions (including cognitive behavioural therapy,
      supportive counselling, psychotherapy, self-regulatory techniques, mindfulness
      based cognitive therapy and disclosure therapy) provided as an adjunct to
      medication, 2) included rheumatoid arthritis patients aged >= 18 years, 3)
      reported findings for at least 1 of the primary outcomes: pain, fatigue,
      psychological status, functional disability and disease activity and 4) were
      published in English between January 2000 and March 2015 (updated January 2018).
      DATA SOURCES: We searched in MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane
      Database of Systematic Reviews and the Database of Abstracts of Reviews of
      Effects. Reference lists were searched for additional reviews. REVIEW METHODS:
      Study selection and 50% of the quality assessments were performed by two
      independent reviewers. Methodological quality was measured using the Assessment
      of Multiple Systematic Reviews checklist. Data extraction was conducted by one
      reviewer using a predesigned data extraction form. RESULTS: Eight systematic
      reviews met inclusion criteria (one review was excluded due to its low-quality
      score). Small post intervention improvements in patient global assessment,
      functional disability, pain, fatigue, anxiety and depression were observed. The
      effect on coping, self-efficacy and physical activity was greater. Improvements
      in depression, coping and physical activity were maintained (8.5-14 months).
      Interventions delivered over a longer period with a maintenance component
      appeared more effective. Attention, education, and placebo control groups
      produced some improvements but not as large as those produced by the
      psychological interventions. CONCLUSIONS: Psychological interventions result in
      small to moderate improvements in biopsychosocial outcomes for patients with
      rheumatoid arthritis in addition to those achieved by standard care. Several
      priorities for future research were identified, including determining the cost
      effectiveness of non-psychologically trained health professionals delivering
      psychological interventions.

PMID- 29573594
TI  - Looking but not seeing: Increased eye fixations in behavioural-variant
      frontotemporal dementia.
AB  - Face processing plays a central role in human communication, with the eye region
      a particularly important cue for discriminating emotions. Indeed, reduced
      attention to the eyes has been argued to underlie social deficits in a number of
      clinical populations. Despite well-established impairments in facial affect
      recognition in behavioural-variant frontotemporal dementia, whether these
      patients also have perturbed facial scanning is yet to be investigated. The
      current study employed eye tracking to record visual scanning of faces in 20
      behavioural-variant frontotemporal dementia patients and 21 controls. Remarkably,
      behavioural-variant frontotemporal dementia patients displayed more fixations to
      the eyes of emotional faces, compared to controls. Neural regions associated with
      fixations to the eyes included the left inferior frontal gyrus, right cerebellum
      and middle temporal gyrus. Our study is the first to show such compensatory
      functions in behavioural-variant frontotemporal dementia and suggest a feedback
      style network, including anterior and posterior brain regions, is involved in
      early face processing.

PMID- 29573595
TI  - Post-traumatic stress and relationships to coping and alexithymia in patients
      with psychogenic non-epileptic seizures.
AB  - PURPOSE: There is increasing evidence that patients with PNES can form subgroups
      distinguished by emotion dysregulation and comorbid psychological symptoms. The
      purpose of this study was to determine if patients with comorbid PTSD differ from
      other patients with PNES in terms of alexithymia and stress coping strategies.
      METHODS: 156 adult patients with video-EEG confirmed PNES were assessed with the
      Trauma Symptom Inventory-2 (TSI-2) and diagnostic clinical interview, Toronto
      Alexithymia Scale (TAS-20), and the Coping Inventory for Stressful Situations
      (CISS). There were 3 groups: 48 patients with PTSD, 62 patients who had
      experienced trauma and did not have PTSD, and 46 patients who denied experiencing
      trauma. RESULTS: One-way ANCOVA revealed a significant difference between groups
      on reported levels of alexithymia [F(2, 154) = 18.21, p < .001] and use of
      emotion-focused coping [F(2, 156) = 11.12, p < .001]. Tukey HSD post-hoc
      comparisons indicated that the PNES/PTSD group had significantly higher mean
      alexithymia scores (M = 59.54, SD = 12.89) than both the no trauma (M = 49.51, SD
      = 14.92) and the trauma with no PTSD groups (M = 49.98, SD = 13.27), which did
      not differ from each other. The PNES/PTSD group was also significantly more
      likely (M = 62.44, SD = 11.56) than the no trauma (M = 52.87, SD = 13.57) and the
      trauma with no PTSD groups (M = 52.06, SD = 12.63) to utilize emotion-focused
      coping strategies. No significant differences were found between groups on use of
      task- or avoidance-focused coping. CONCLUSION: The study revealed elevated
      alexithymia and use of potentially more maladaptive emotion-focused coping
      strategies among patients with PNES and comorbid PTSD. These findings highlight
      discrete areas to target in treatment depending on comorbid symptomatology, and
      suggests that PNES, which is often regarded as a homogeneous entity, appears to
      encompass distinct subgroups.

PMID- 29573596
TI  - Lemierre's syndrome following perianal abscess: A case report.
AB  - INTRODUCTION: Lemierre's syndrome (LS) is a rare and life-threatening condition
      characterized by suppurative thrombophlebitis of the internal jugular vein (IJV),
      and a history of head and neck (H&N) sepsis. LS is usually caused by
      Fusobacterium necrophorum, which is part of the normal flora in the oro-pharynx,
      and the digestive and urogenital tracts. We here report the first case of LS
      following perianal sepsis. PRESENTATION OF CASE: A 60-year-old man with a painful
      left neck swelling, dysphagia and worsening sepsis was referred from a peripheral
      unit where he had an incision and drainage of a perianal abscess a week earlier.
      Urgent Doppler ultrasound and computed tomographic scans demonstrated suppurative
      thrombophlebitis of the left IJV, and the patient was subsequently commenced on
      intravenous Piperacillin/Tazobactam and heparin. The symptoms gradually improved,
      and the patient was eventually discharged on the 10th day. DISCUSSION: Vigilant
      examination of the H&N region searching for a primary source is paramount, but LS
      following infections in the gastrointestinal or uro-genital tracts has also been
      described. A high index of suspicion is required for diagnosis, especially in
      patients with unresolving pharyngitis with a unilateral neck swelling, and
      septicaemia. Early resuscitation and treatment with broad-spectrum parenteral
      antimicrobials are important for favourable outcome. CONCLUSION: LS is well known
      to specialists in the H&N region, but other disciplines like general surgery,
      urology, or obstetrics and gynaecology might also rarely encounter the disease.
      We present a case of LS complicating a perianal abscess that was successfully
      treated with good outcome.

PMID- 29573597
TI  - Laparoscopic Roux-en-Y gastric bypass in a patient with situs inversus totalis:
      Case report, technical tips and review of the literature.
AB  - INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has proven over the
      years to be one of the most effective bariatric procedures. It is highly
      technical, and therefore is mostly performed by bariatric and metabolic surgeons.
      Although Situs Inversus Totalis (SIT) is a very rare congenital condition,
      surgeons do occasionally have to operate intra-abdominally on those patients,
      consequently facing some challenges related to the unusual anatomy. CASE
      PRESENTATION: We describe a rare case of LRYGB for chronic morbid obesity on a 43
      year old patient with pre-operative diagnosis of situs inversus totalis without
      Kartagener's syndrome, using slight modification from the usual technique based
      on anatomical correlation without the need to change the surgeon's position or
      switching trocar placements as described in previous papers. This could help
      surgeons in general reduce the potential challenges faced when performing such
      procedure. CONCLUSION: Situs Inversus Totalis is a rare congenital condition, but
      surgeons in general do encounter those patients throughout their career. This
      rare condition should not solely be an indication for an open approach as
      minimally invasive surgery, whether laparoscopic or robotic, is safe and should
      still be considered the standard of care approach. Bariatric surgery is one of
      the most technical intra-abdominal procedures mainly due to the patients' body
      habitus, different instrumentations used, and the different anastomoses created.
      Gastric bypass and bariatric surgery in general can be safely performed on
      patients with SIT without the need for major adjustment to the surgeon's
      position, trocar placement or instruments used.

PMID- 29573598
TI  - Clinical value of 11C-methionine positron emission tomography in persistent
      primary hyperparathyroidism-A case report with a mediastinal parathyroid adenoma.
AB  - INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common endocrine disorder
      caused by pathologic growth of one or more of the parathyroid glands.
      Parathyroidectomies (PTX) in patients with PHPT are procedures with low
      morbidity, few complications, and a high cure rate. However, the parathyroid
      glands may be found at various anatomical locations and occasionally they are
      intrathoracic. CASE PRESENTATION: We present a 57-year-old patient with PHPT.
      Before the first and second operation, the preoperative imaging indicated
      pathologic parathyroid tissue in the neck. Due to postoperative persistent
      hypercalcemia we performed a 11C-methionine positron emission tomography (11C-MET
      PET/CT). The scan showed a focus with increased activity in the mediastinum. Due
      to persistent disease, an ectopic parathyroid gland in the mediastinum was
      suspected. At a third operation, the parathyroid adenoma was resected through an
      anterolateral thoracotomy. Biochemical values normalized and bone mineral density
      improved postoperatively. Hence, an ectopic localization of a parathyroid gland
      should be considered during the preoperative planning of a PTX, especially in the
      re-operative setting. A multidisciplinary effort is necessary to address an
      intrathoracic adenoma. CONCLUSION: Ectopic parathyroid glands should be suspected
      when positive sestaMIBI uptake is seen in the mediastinum and other types of
      imaging (e.g. contrast enhanced CT scan or PET-CT) may confirm the finding of an
      ectopic parathyroid adenoma. From the present case and previous studies we found
      11C-MET-PET/CT valuable in difficult PHPT cases.

PMID- 29573599
TI  - Perforation of abdominal esophagus following nasogastric feeding tube intubation:
      A case report.
AB  - INTRODUCTION: Perforation of the abdominal esophagus caused by nasogastric tube
      (NGT) intubation has been rarely reported in adults. PRESENTATION OF CASE: A 73
      year-old man was admitted to our hospital with pneumonia. He had been bedridden
      long-term and had previously undergone a gastrectomy for gastric ulcer. Since
      admission was prolonged, and he required enteral feeding because of his inability
      to swallow, a NGT was inserted blindly. The next day, he had a high fever and
      abdominal pain. Abdominal computed tomography scan revealed that the tube was
      inserted through the wall of the abdominal esophagus into the abdominal cavity.
      In the emergency surgery, we sutured the perforated site of abdominal esophagus
      and patched it with lesser omentum. The postoperative course was good.
      DISCUSSION: Abdominal esophageal perforation due to NGT insertion is very rare.
      The cause of perforation was suggested to be an abnormal deformity created by
      adhesion due to previous distal gastrectomy and long-term bedridden status. A
      chest X-ray usually is performed to confirm the position of the NGT tube. In this
      case, a frontal radiographic view apparently showed the NGT placed in the
      stomach. CONCLUSION: When NGT is inserted to such patients, frontal and lateral
      radiographic views or fluoroscopic guidance should be obtained.

PMID- 29573600
TI  - Epidural angiolipoma: A rare cause of spinal cord compression.
AB  - INTRODUCTION: Angiolipomas are benign, slow growing lesions, almost always
      located subcutaneously in the trunc or limbs. They are composed of mature
      lipocytes admixed with abnormal blood vessels. Spinal epidural angiolipoma are
      rare accounting for approximately 0.14-1.2% of all spinal axis tumors and 2-3% of
      epidural spinal tumors. PRESENTATION OF CASE: We report the case of a 65 years
      old-woman, presenting with complete paraplegia installed since 7 months. Magnetic
      resonance imaging (MRI) showed an epidural dorsal fatty mass. The patient
      recovered immediately after surgery. The pathological examination concluded to an
      angiolipoma. DISCUSSION: Angiolipoma patients most commonly have long-lasting
      pain and then develop progressive neurological symptoms secondary to spinal cord
      compression. The mean duration of symptom progression at diagnosis is 1 year. MRI
      is the most reliable examination for the diagnosis of spinal angiolipoma. Total
      resection is the treatment of choice. No adjuvant treatment is indicated. Since
      SAL are very haemorrhagic lesions, preoperative embolization is recommended.
      CONCLUSION: We think that spinal cord compression caused by angiolipoma have very
      good functional prognosis, even if tardily diagnosed.

PMID- 29573601
TI  - Measuring and assessing risk of quality of life loss following a road traffic
      injury: A proposed methodology for use of a composite score.
AB  - INTRODUCTION: Assessments of the impact of road traffic injuries (RTIs) on
      quality of life (QoL) can benefit from the use of combined characteristics of the
      injurious event. AIM: The burden of having sustained a RTI was computed using a
      composite score that comprised three elements (i.e. number of injuries sustained
      in the crash, body parts affected, and severity of the injuries) that relate to
      the probability of subsequent long-term QoL lost by individuals 1-4 years after
      the crash. METHODOLOGY: The QoL of injured victims aged 11-90 years that crashed
      in Sweden between 2007 and 2009 was compared with that of a random sample of non
      injured individuals frequency-matched by sex and age. Injury information to build
      the composite score was obtained from a national register that contains data on
      the number of injuries, their severity, and the body parts affected. The QoL was
      assessed in 2010 for both injured and non-injured individuals using the
      standardized Euro Quality of Life questionnaire. Logistic regression was used to
      investigate whether the composite score was predictive of low QoL (<90% of the
      mean of non-injured referents) adjusting for sex, age, and time elapsed since the
      injury occurrence. The composite score was grouped into five exposure categories
      (0.01-1, 1.01-1.5, 1.51-2, 2.01-3 and 3.01-9 units). RESULTS: Compared with the
      non-injured reference group, all exposure categories showed statistically
      significant increased adjusted ORs for low QoL ranging from 2.35 (95% CI 1.48
      3.72) in the 0.01-1.00 lowest injury category to 6.10 (95% CI 3.65-10.2) in the
      highest 3.01-9.00 with a slightly decreasing plateau in the intermediate
      categories (point ORs between 3.86 and 3.06). Yet, all 95% CIs across the
      exposure categories overlapped. CONCLUSION: Long-term reduction in QoL is a
      burden experienced by the victims of mild to severe RTCs. The proposed composite
      score can be an initial step in the development of more elaborated instruments
      that can be useful in policy making and regulation.

PMID- 29573602
TI  - Similarities and differences between families who have frequent and infrequent
      family meals: A qualitative investigation of low-income and minority households.
AB  - INTRODUCTION: Numerous quantitative studies have examined the association between
      family meal frequency and child/adolescent weight and weight-related behaviors.
      However, limited qualitative research has been conducted to identify mealtime
      characteristics (e.g., child behavior during meals, rules/expectations, family
      dynamics) that occur during family meals that may explain why some families
      engage in frequent family meals and others do not. This is particularly important
      within racially/ethnically diverse households, as these demographic groups are at
      higher risk for weight-related problems. The current study aimed to identify
      similarities and differences in mealtime characteristics between households that
      have frequent and infrequent family meals within a low-income and minority
      population. METHODS: This qualitative study included 118 parents who participated
      in Family Meals, LIVE!, a mixed-methods, cross-sectional study. Parents (90%
      female; mean age = 35) were racially/ethnically diverse (62% African American,
      19% White, 4% Native American, 4% Asian, 11% Mixed/Other) and from low-income
      (73% < $35,000/yr.) households. Data were analyzed using inductive content
      analysis. RESULTS: Results indicated some similar mealtime characteristics (i.e.,
      picky eating, involving family members in meal preparation) between households
      having frequent and infrequent family meals. Additionally, several differences in
      mealtime characteristics were identified between households having frequent
      (i.e., importance of family meals, flexibility in the definition of family meals,
      family meal rules, no pressure-to-eat feeding practices) versus infrequent family
      meals (i.e., pressure-to-eat parent feeding practices, family meals are dinner
      meals only, and difficult meal time behaviors). DISCUSSION: Study findings may be
      useful for developing intervention targets for low-income and racially/ethnically
      diverse households so more families can benefit from the protective nature of
      family meals.

PMID- 29573603
TI  - Metabolomic analysis of short-term sulfamethazine exposure on marine medaka
      (Oryzias melastigma) by comprehensive two-dimensional gas chromatography-time-of
      flight mass spectrometry.
AB  - Toxicological effects of sulfamethazine (SM2) have garnered increasing concern
      due to its wide applications in aquaculture and persistence in the aquatic
      environment. Most studies have main focused on freshwater fish (i.e. zebrafish),
      while information regarding effects of SM2 on marine species is still scarce.
      Here, the hepatotoxicities in marine medaka (Oryzias melastigma) with an
      increasing SM2 concentration exposures (0.01 mg/L, 0.1 mg/L and 1 mg/L) were
      assessed by comprehensive two-dimensional gas chromatography-time-of-flight mass
      spectrometry (GC * GC-TOF/MS) based metabolomics. Significant metabolites
      belonging to different metabolites classes were identified by multivariate
      statistical analysis. The increases levels of amino acids including alanine,
      asparagine, ornithine, proline, threonine, glutamic acid, lysine, tyrosine and
      phenylalanine were found in at least two exposure levels. Pathway analysis
      revealed that amino acids played important biological roles during SM2 exposure:
      up-regulation of high energy-related amino acids for energy alteration; immune
      function disorder, oxidative stress and corresponding toxicities defenses. The
      down regulations of sugar and fatty acid metabolism were observed with an
      increasing level of SM2 exposure, suggesting that extra energy for cellular
      defense and detoxification was demanded in terms of different stress request.
      This study provided an innovative perspective to explore possible SM2 induced
      hepatic damages at three exposure levels on a nontarget aquatic specie.

PMID- 29573604
TI  - Value of the combination of renal resistance index and central venous pressure in
      the early prediction of sepsis-induced acute kidney injury.
AB  - PURPOSE: Early prediction of acute kidney injury (AKI) in septic patients is
      difficult. This study aimed to assess the values of renal resistive index (RI),
      central venous pressure (CVP), and their combination in the early prediction of
      sepsis-induced AKI. METHODS: A prospective cohort study was performed in septic
      patients. The variables potentially associated with AKI were recorded at
      admission and compared between the AKI and non-AKI groups. The variables
      independently associated with sepsis-induced AKI were identified using
      multivariable logistic regression, and the area under the receiver operating
      characteristic curve (AUROC) analysis was calculated. RESULTS: A total of 124
      septic patients were included. Septic shock (OR, 3.28; P=0.002), high CVP (OR,
      1.92; P=0.012) and renal RI (OR, 2.58; P=0.009), low diastolic perfusion pressure
      (DPP) (OR, 2.15; P=0.010) at admission were independent risk factors for sepsis
      induced AKI. The AUROC value of the combination of RI and CVP was greater
      compared with either RI or CVP alone in predicting sepsis-induced AKI
      (AUROC=0.858, 0.811, and 0.780, respectively). CONCLUSIONS: The combination of RI
      and CVP was more valuable than either of the two parameters in the early
      prediction for sepsis-induced AKI.

PMID- 29573605
TI  - Expanded Croatian 12 X-STR loci database with an overview of anomalous profiles.
AB  - In order to implement X-chromosome short tandem repeat (X-STR) typing into
      routine forensic practice, reference database of a given population should be
      established. Therefore we extended already published data with additional 397
      blood samples from unrelated Croatian citizens, and analyzed the total of 995
      samples (549 male and 446 female) typed by Investigator(r) Argus X-12 Kit. To
      test genetic homogeneity of consecutively processed five historic-cultural
      regions covering the entire national territory, we calculated pairwise Fst
      genetic distances between regions based on allele and full haplotype frequencies.
      Since the comparison did not yield any statistically significant difference, we
      integrated STR profile information from all regions and used the whole data set
      to calculate forensic parameters. The most informative marker is DXS10135
      (polymorphism information content (PIC = 0.929) and the most informative linkage
      group (LG) is LG1 (PIC = 0.996). We confirmed linkage disequilibrium (LD) for
      seven marker pairs belonging to LG2, LG3 and LG4. By including LD information, we
      calculated cumulative power of discrimination that amounted to 0.999999999997 in
      females and 0.999999005 in males. We also compared Croatia with 13 European
      populations based on haplotype frequencies and detected no statistically
      significant Fst values after Bonferroni correction in any LG. Multi-dimensional
      scaling plot revealed tight grouping of four Croatian regions amongst populations
      of southern, central and northern Europe, with the exception of northern Croatia.
      In this study we gave the first extensive overview of aberrant profiles
      encountered during Investigator(r) Argus X-12 typing. We found ten profiles
      consistent with single locus duplication followed by tetranucleotide tract length
      polymorphism. Locus DXS10079 is by far the most frequently affected one,
      presumably mutated in eight samples. We also found four profiles consistent with
      X-chromosome aneuploidy (three profiles with XXX pattern and one profile with XXY
      pattern). In conclusion, we established integral forensic Croatian X-chromosome
      database, proved forensic pertinence of Investigator(r) Argus X-12 Kit for the
      entire Croatian population and identified locus DXS10079 as a potential
      duplication hotspot.

PMID- 29573606
TI  - Repair of DNA damage caused by cytosine deamination in mitochondrial DNA of
      forensic case samples.
AB  - DNA sequence damage from cytosine deamination is well documented in degraded
      samples, such as those from ancient and forensic contexts. This study examined
      the effect of a DNA repair treatment on mitochondrial DNA (mtDNA) from aged and
      degraded skeletal samples. DNA extracts from 21 non-probative, degraded skeletal
      samples (aged 50-70 years) were utilized for the analysis. A portion of each
      sample extract was subjected to DNA repair using a commercial repair kit, the New
      England BioLabs' NEBNext FFPE DNA Repair Kit (Ipswich, MA). MtDNA was enriched
      using PCR and targeted capture in a side-by-side experiment of untreated and
      repaired DNA. Sequencing was performed using both traditional (Sanger-type; STS)
      and next-generation sequencing (NGS) methods Although cytosine deamination was
      evident in the mtDNA sequence data, the observed level of damaged bases varied by
      sequencing method as well as by enrichment type. The STS PCR amplicon data did
      not show evidence of cytosine deamination that could be distinguished from
      background signal in either the untreated or repaired sample set. However, the
      same PCR amplicons showed 850 C -> T/G -> A substitutions consistent with
      cytosine deamination with variant frequencies (VFs) of up to 25% when sequenced
      using NGS methods The occurrence of base misincorporation due to cytosine
      deamination was reduced by 98% (to 10) in the NGS amplicon data after repair. The
      NGS capture data indicated low levels (1-2%) of cytosine deamination in mtDNA
      fragments that was effectively mitigated by DNA repair. The observed difference
      in the level of cytosine deamination between the PCR and capture enrichment
      methods can be attributed to the greater propensity for stochastic effects from
      the PCR enrichment technique employed (e.g., low template input, increased PCR
      cycles). Altogether these results indicate that DNA repair may be required when
      sequencing PCR-amplified DNA from degraded forensic case samples with NGS
      methods.

PMID- 29573608
TI  - Thermal decomposition and kinetics of coal and fermented cornstalk using
      thermogravimetric analysis.
AB  - The thermal behavior and kinetics of Yiluo coal (YC) and the residues of
      fermented cornstalk (FC) were investigated in this study. The Kissinger-Akahira
      Sunose (KAS) and Flynn-Wall-Ozawa (FWO) methods were used for the kinetic
      analysis of the pyrolysis process. The results showed that the activation energy
      (Ealpha) was increased with the increase of the thermal conversion rate (alpha),
      and the average values of Ealpha of YC, FC and the blend (mYC/mFC = 6/4) were
      304.26, 224.94 and 233.46 kJ/mol, respectively. The order reaction model function
      for the blend was also developed by the master-plots method. By comparing the Ea
      and the enthalpy, it was found that the blend was favored to format activated
      complex due to the lower potential energy barrier. Meanwhile, the average value
      of Gibbs free energy of the blend was 169.83 kJ/mol, and the changes of entropies
      indicated that the pyrolysis process was evolved from ordered-state to disordered
      state.

PMID- 29573607
TI  - Substrates removal and growth kinetic characteristics of a heterotrophic
      nitrifying-aerobic denitrifying bacterium, Acinetobacter harbinensis HITLi7T at 2
      degrees C.
AB  - In order to investigate the heterotrophic nitrification and aerobic
      denitrification ability of Acinetobacter harbinensis HITLi7T at 2  degrees C,
      both the growth parameters and substrates utilization characteristics were tested
      and appropriated kinetic models were obtained in this study. Under the initial
      concentration of 5 mg/L, the maximum NH4+-N and NO3--N degradation rates were
      0.076 mg NH4+-N/L/h and 0.029 mg NO3--N/L/h, respectively. At the simultaneous
      presence of 2.5 mg/L NH4+-N and NO3--N, the maximum nitrate removal rate
      increased to 0.054 mg NO3--N/L/h (1.86 folds), while a slight decrease was
      observed in NH4+-N removal. Two double-substrate models, Contois-Contois (1) for
      NH4+-N and TOC, Monod-Contois (2) for NO3--N and TOC matched well with the
      experimental data. The kinetic parameters were determined as MUmax1 = 0.095 h-1,
      BA1 = 0.012 mg/L, BT1 = 0.784 g TOC/g biomass (R12 = 0.9997), and MUmax2 = 0.032
      h-1, KN2 = 0.375 mg/L, BT2 = 1.108 g TOC/g biomass (R22 = 0.9731) by multiple
      regression equation.

PMID- 29573609
TI  - Specific enrichment of hyperthermophilic electroactive Archaea from deep-sea
      hydrothermal vent on electrically conductive support.
AB  - While more and more investigations are done to study hyperthermophilic
      exoelectrogenic communities from environments, none have been performed yet on
      deep-sea hydrothermal vent. Samples of black smoker chimney from Rainbow site on
      the Atlantic mid-oceanic ridge have been harvested for enriching exoelectrogens
      in microbial electrolysis cells under hyperthermophilic (80  degrees C)
      condition. Two enrichments were performed in a BioElectrochemical System
      specially designed: one from direct inoculation of crushed chimney and the other
      one from inoculation of a pre-cultivation on iron (III) oxide. In both
      experiments, a current production was observed from 2.4 A/m2 to 5.8 A/m2 with a
      set anode potential of -0.110 V vs Ag/AgCl. Taxonomic affiliation of the
      exoelectrogen communities obtained on the electrode exhibited a specific
      enrichment of Archaea belonging to Thermococcales and Archeoglobales orders, even
      when both inocula were dominated by Bacteria.

PMID- 29573610
TI  - A novel modification of lignin on corncob-based biochar to enhance removal of
      cadmium from water.
AB  - In order to improve the adsorption capacities of corncob-based biochars for heavy
      metal, the different pyrolysis temperature (350  degrees C, 450  degrees C and
      550  degrees C) of corncob-based biochars were modified with the acrylonitrile,
      and adsorption capacities of Cadmium from solution by biochars were studied. The
      results showed that only at 350  degrees C the biochar can be successfully
      modified. The Cd adsorption capacity (85.65 mg/g) by the biosorbent was higher
      than other methods of modifying biochars previously reported. SEM-EDS and FTIR
      confirmed that the CN group was grafted on the biochar at low pyrolysis
      temperature. Batch adsorption experiment including pH-dependence, adsorption
      kinetics, and isotherms and XPS results showed that the removal mechanism of
      Cd(II) by the modified biochar was ion exchange and adsorption-complexation. This
      research not only obtained a novel method to modify biochar but also furthered
      research into the lignin of biochar composition, and provided an efficient
      sorbent for heavy metal.

PMID- 29573611
TI  - Kinetic analysis of curdlan production by Alcaligenes faecalis with maltose,
      sucrose, glucose and fructose as carbon sources.
AB  - Curdlan has wide-ranging benefits in food and pharmaceutical industries for its
      unique rheological and thermal gelling properties. To analyze the cell growth and
      curdlan biosynthesis kinetics of Alcaligenes faecalis, the kinetic properties of
      the curdlan fermentation under different carbon sources conditions (maltose,
      sucrose, glucose and fructose) were investigated using Logistic and Luedeking
      Piret equations. The results demonstrated that curdlan fermentation is partial
      growth-associated process. With maltose as the sole carbon source, the highest
      curdlan production (Pm = 39.3 g/L), the maximum specific growth rate (MUm =
      0.44/h) and the growth-associated rate constant (alpha = 2.05 g curdlan/g cell)
      were achieved. In contrast, the fructose was the less desired carbon source in
      both the cell growth and curdlan production. Further, the results demonstrated
      that slow-releasing glucose from maltose boosted cell growth and curdlan
      production.

PMID- 29573612
TI  - Isolation of new cellulase and xylanase producing strains and application to
      lignocellulosic biomasses hydrolysis and succinic acid production.
AB  - The enzymatic extracellular mixtures of two new microorganisms - Streptomyces
      flavogriseus AE64X and AE63X - isolated from Eucalyptus camaldulensis and Populus
      nigra and producing cellulase and xylanase, were characterized and applied to
      hydrolysis of pretreated Arundo donax, Populus nigra and Panicum virgatum (10%
      w/v) replacing the commercial enzymes Accelerase 1500 and Accelerase XY (5.4 and
      145 U/g of pretreated biomass, respectively). It is worth of noting that the
      newly developed extracellular enzymatic mixtures, without any purification step
      and at the same dosage, presented saccharification yields that are higher (86%
      for S. flavogriseus AE64X) than those of commercial enzymes (81%). Moreover,
      these enzymatic mixes allowed us to hydrolyse both cellulose and xylan within the
      different lignocellulose biomasses substituting both the cellulase and xylanase
      of commercial source. The produced sugars were also fermentable by Basfia
      succiniciproducens BPP7 into succinic acid with high yield.

PMID- 29573613
TI  - Improvement of cadmium phytoremediation by Centella asiatica L. after soil
      inoculation with cadmium-resistant Enterobacter sp. FM-1.
AB  - This study examined the potential of a cadmium-resistant Enterobacter sp. FM-1 to
      promote plant growth and assist in cadmium accumulation in both mine-type C.
      asiatica L. and non-mine type C. asiatica L. tissues in highly cadmium-polluted
      soils. The results indicated that Enterobacter sp. FM-1 significantly promoted
      growth and alleviated metal toxicity in both types of C. asiatica L. Meanwhile,
      inoculation with Enterobacter sp. FM-1 in contaminated soil can increased cadmium
      bioavailability in soil. Furthermore, it will increase plant uptake and the
      accumulation of cadmium in C. asiatica L. leaves, stems and roots compared to
      that in an uninoculated plant. However, mine-type C. asiatica L. had better
      cadmium tolerance than the non mine-type C. asiatica L. Because of its native
      metal-tolerant ability, which could easily grow and proliferate, and had a better
      performance under cadmium-contamination conditions. Additionally, inoculation
      with Enterobacter sp. FM-1 significantly enhanced the bioaccumulation factor
      (BAF) and the translocation factor (TF) values in both types of C. asiatica L.
      even under high cadmium concentration soil condition. Hence, based on higher BAF
      and TF values and strong cadmium accumulation in the leaves and stems, we
      concluded that inoculation with Enterobacter sp. FM-1 is potentially useful for
      the phytoremediation of cadmium-contaminated sites by Centella asiatica L.

PMID- 29573614
TI  - Effects of glyphosate and its commercial formulation, Roundup(r) Ultramax, on
      liver histology of tadpoles of the neotropical frog, Leptodactylus latrans
      (amphibia: Anura).
AB  - In the last years, the agricultural expansion has led to an increased use of
      pesticides, with glyphosate as the most widely used worldwide. This is also the
      situation in Argentina, where glyphosate formulations are the most commercialized
      herbicides. It is known that glyphosate formulations are much more toxic than the
      active ingredient, and this difference in toxicity can be attributed to the
      adjuvants present in the formula. In this context, the aim of the present study
      was to evaluate and compare sub-lethal histological effects of the glyphosate
      formulation Roundup Ultramax and glyphosate active ingredient on Leptodactylus
      latrans tadpoles at Gosner-stage 36. Semi-static bioassays were performed using
      96 h of exposure with Roundup Ultramax formulation (RU; 0.37-5.25 mg a.e./L),
      glyphosate (GLY; 3-300 mg/L), and a control group. RU exposure showed an
      increment in the melanomacrophagic cells (MMc) and melanomacrophagic centers
      (MMCs) from 0.37 mg a.e./L. GLY exposure showed a significant increment in the
      number of MMc from 15 mg/L, and of MMCs from 3 mg/L. Also, histopathological
      lesions were observed in the liver of tadpoles exposed to both, GLY and RU. These
      lesions included: lipidosis and hepatic congestion, but only RU showed
      significant differences respect to control, with a LOEC value of 2.22 mg a.e./L
      for both effects. In sum, this study represents the first evidence of adverse
      effects of glyphosate and RU formulation on the liver of anuran larvae at
      concentrations frequently found in the environment.

PMID- 29573615
TI  - The preparation of carboxylic-functional carbon-based nanofibers for the removal
      of cationic pollutants.
AB  - A simple route is presented to fabricate carboxylic-functional carbon-coated
      polyacrylonitrile nanofibers (oPAN@C) through preoxidation and hydrothermal
      carbonization. PAN fibers were firstly preoxidized to form aromatic ladder
      structure with the resistance to hydrothermal condition, in which more carboxyl
      groups were introduced on the fiber surface at the present of chitosan and citric
      acid. The oPAN@C composites exhibit a high adsorption capacity towards methylene
      blue (MB) and lead ion (Pb2+). The adsorption data matched the pseudo-second
      order kinetic model and Langmuir model well with the maximum adsorption capacity
      (153.37 and 143.27 mg g-1) for methylene blue and Pb2+, respectively. Moreover,
      oPAN@C could be regenerated easily by hydrochloric acid, and still remained high
      removal efficiency after 5 cycles. Therefore, oPAN@C fibers should have potential
      application in sewage treatment.

PMID- 29573616
TI  - Changes in microbial communities during volatile fatty acid production from
      cyanobacterial biomass harvested from a cyanobacterial bloom in a river.
AB  - Volatile fatty acid (VFA) production, utilization of soluble organic compounds,
      and associated microbial consortia were investigated after different
      pretreatments (untreated, alkaline, and thermal-alkaline) using cyanobacterial
      biomass as a substrate. Compared to the untreated control, soluble carbohydrate
      concentrations were almost the same after alkaline and thermal-alkaline
      pretreatments, but soluble protein concentration was 1.58 times higher after
      alkaline pretreatment and 1.81 times higher after thermal-alkaline pretreatment.
      However, the highest degree of acidification was obtained after alkaline
      pretreatment (55.36 +/- 3.00%). Microbial communities in the untreated control
      differed only slightly from those after thermal-alkaline pretreatment, but were
      clearly distinct from those after alkaline pretreatment. After alkaline
      pretreatment, protein-utilizing bacteria became relatively predominant. These
      results revealed the relationships between efficiency of VFA production and the
      shift in microbial community.

PMID- 29573617
TI  - Anti-arrhythmogenic and anti-inflammatory effects of troxerutin in
      ischemia/reperfusion injury of diabetic myocardium.
AB  - INTRODUCTION: Medicinal plants are increasingly used in the treatment of
      cardiovascular diseases due to their multifaceted properties. This study was
      designed to investigate anti-arrhythmic and anti-inflammatory potentials of the
      natural bioflavonoid, troxerutin (TXR) in myocardial ischemia/reperfusion (I/R)
      injury in diabetic rats. METHODS: Male Wistar rats were randomly divided into 4
      groups (control, control + TXR [150 mg/kg, daily], diabetic, and diabetic + TXR).
      Type-1 diabetes was induced by an intraperitoneal injection of streptozotocin (50
      mg/kg) and lasted for 10 weeks. After mounting on the Langendorff apparatus,
      isolated hearts in all groups received a normal Krebs-Henseleit solution for 20
      min of stabilization period, followed by 30 min of regional ischemia through
      ligation of the left anterior descending coronary artery, and 60 min of full
      reperfusion. During the experiment, the electrocardiograms were recorded and the
      arrhythmias [number, duration and incidence of premature ventricular complexes
      (PVC), ventricular tachycardia (VT), ventricular fibrillation (VF), and
      arrhythmia score] during I/R phases were assessed based on the Lambeth
      Convention. Ischemic left ventricular samples were used to determine the
      activities of lactate dehydrogenase (LDH), interleukin-1beta (IL-1beta), and
      tumor necrosis factor (TNF-alpha). RESULTS: The arrhythmias induced by I/R were
      not significantly changed in diabetic group as compared to the control group.
      However, pretreatment with TXR significantly reduced the number of PVC and
      duration and incidence of VF in ischemic phase in comparison to the untreated
      animals (P < 0.05). In addition, the duration, and incidence of most arrhythmias
      during reperfusion phase were significantly declined by TXR administration in
      both control and diabetic groups (P < 0.05). Pretreatment of rats with TXR
      significantly reduced myocardial inflammatory cytokines TNF-alpha and IL-1beta
      levels after I/R insult in diabetic as well as control hearts (P < 0.05).
      CONCLUSION: Preconditioning with TXR could provide cardioprotection by anti
      arrhythmic and anti-inflammatory effects against I/R injury in rat hearts. This
      effect of TXR can introduce this material as a protective agent in cardiovascular
      diseases.

PMID- 29573618
TI  - Umbelliferone prevents oxidative stress, inflammation and hematological
      alterations, and modulates glutamate-nitric oxide-cGMP signaling in
      hyperammonemic rats.
AB  - Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that
      occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a
      natural product with proven hepatoprotective activity; however, nothing has yet
      been reported on its protective effect against hyperammonemia, the main culprit
      behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium
      chloride (NH4Cl)-induced hyperammonemia, oxidative stress, inflammation and
      hematological alterations in rats. We demonstrated the modulatory role of UMB on
      the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats
      received intraperitoneal injections of NH4Cl (3 times/week) for 8 weeks and
      concomitantly received 50 mg/kg UMB. NH4Cl-induced rats showed significantly
      elevated blood ammonia and liver function markers. Lipid peroxidation and NO were
      increased in the liver and cerebrum of rats while the antioxidant defenses were
      declined. UMB significantly reduced blood ammonia, liver function markers, lipid
      peroxidation and NO, and enhanced the antioxidant defenses in NH4Cl-induced rats.
      UMB significantly prevented anemia, leukocytosis, thrombocytopenia and
      prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of
      cerebral TNF-alpha, IL-1beta and glutamine as well as increased activity and
      expression of Na+/K+-ATPase, effects that were significantly reversed by UMB. In
      addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase
      in the cerebrum of hyperammonemic rats. In conclusion, this study provides
      evidence that UMB protects against hyperammonemia via attenuation of oxidative
      stress and inflammation. UMB prevents hyperammonemia associated hematological
      alterations and therefore represents a promising protective agent against the
      deleterious effects of excess ammonia.

PMID- 29573619
TI  - Estrogen: The necessary evil for human health, and ways to tame it.
AB  - Estrogen is a pivotal enzyme for survival and health in both genders, though
      their quantum, tropism, tissue-specific distribution, and receptor affinity
      varies with different phases of life. Converted from androgen via aromatase
      enzyme, this hormone is indispensable to glucose homeostasis, immune robustness,
      bone health, cardiovascular health, fertility, and neural functions. However,
      estrogen is at the center of almost all human pathologies as well-infectious,
      autoimmune, metabolic to degenerative. Both hypo and hyper level of estrogen has
      been linked to chronic and acute diseases. While normal aging is supposed to
      lower its level, leading to tissue degeneration (bone, muscle, neural etc.), and
      metabolite imbalance (glucose, lipid etc.), the increment in inflammatory agents
      in day-to-day life are enhancing the estrogen (or estrogen mimic) level, fueling
      'estrogen dominance'. The resultant excess estrogen is inducing an overexpression
      of estrogen receptors (ERalpha and ERbeta), harming tissues, leading to
      autoimmune diseases, and neoplasms. The unprecedented escalation in the
      polycystic ovary syndrome, infertility, breast cancer, ovary cancer, and
      gynecomastia cases are indicating that this sensitive hormone is getting
      exacerbated. This critical review is an effort to analyze the dual, and opposing
      facets of estrogen, via understanding its crosstalk with other hormones, enzymes,
      metabolites, and drugs. Why estrogen level correction is no trivial task, and how
      it can be restored to normalcy by a disciplined lifestyle with wise dietary and
      selective chemical usage choices has been discussed. Overall, our current state
      of knowledge does not disclose the full picture of estrogen's pleiotropic
      importance. Hence, this review should be a resource for general public as well as
      researchers to work in that direction.

PMID- 29573620
TI  - Sesquiterpenoids from the root of Panax Ginseng protect CCl4-induced acute liver
      injury by anti-inflammatory and anti-oxidative capabilities in mice.
AB  - The oxidative stress and inflammatory response play an important role in carbon
      tetracholoride (CCl4)-induced acute liver injury. In this work, sesquiterpenoids
      from the root of Panax Ginseng (SPG) were prepared, and then the hepatoprotective
      effects of SPG against CCl4-induced acute liver injury were investigated and the
      underlying mechanism was explored in mice. All mice were divided into four
      groups: the control, CCl4 and SPG (2.5 and 10 mg/kg, dissolved in soybean oil,
      i.g.) groups. All mice were given continuous administration for 7 days, and
      injected with CCl4 (0.1 mL/10 g body weight 0.2% CCl4 solution in soybean oil,
      i.p.) 1 h after the end of the administration except the control group. Mice were
      sacrificed 24 h post-CCl4 injection. The results indicated that SPG significantly
      reduced the increasement of serum AST and ALT levels induced by CCl4-treatment.
      And the histopathological analysis revealed that SPG treated mice had normal
      liver architecture and no necrosis. The decreased activities of SOD, GSH and CAT,
      and increased MDA level were inhibited by SPG treatment. At the same time, the
      levels of TNF-alpha, IL-1beta and IL-6 were significantly decreased by SPG
      treatment. SPG treatment also reduced the heptic protein expressions of NF-kappaB
      p65, COX-2, MAPK p38, ERK and JNK in the liver. These fingdings demonstrated that
      SPG exhibited strong hepatoprective effect on the CCl4-induced acute liver
      injury, which was related to anti-oxidantive and anti-inflammatory capabilities;
      and the anti-inflammatory effect of SPG might mediated by the NF-kappaB and MAPKs
      signaling pathways. Taken together, SPG might be a potential material for drug
      and functional food development against chemical hepatic injury.

PMID- 29573621
TI  - Photoelectrochemical TiO2 nanotube arrays biosensor for asulam determination
      based on in-situ generation of quantum dots.
AB  - Inspired by the photoelectrochemical (PEC) properties of TiO2 nanotubes arrays
      (TNA) and their application as a super vessel for immobilizing biomolecules, we
      constructed an inhibition-effect PEC biosensor for determination of asulam based
      on the in-situ generation of CdS quantum dots (QDs) on TNA using an enzymatic
      reaction. Horseradish peroxidase (HRP) enzyme was covalently assembled on the
      inner-wall of TNAs, which exhibited good electrochemical and catalytic
      properties. In the mixture solution containing H2O2, CdY and S2O32-, HRP enzyme
      in TNAs catalyzed H2O2 reduce S2O32- to S2-. The generated S2- reacted with CdY
      to form CdS QDs in situ on the TNAs, improving the PEC performance of TNA under
      visible light irradiation. The photocurrent would decrease after addition of
      asulam due to its inhibitory effect towards HRP enzyme activity. Under the
      optimal experimental conditions, the constructed PEC TNA/HRP biosensor exhibited
      a satisfying linear range (0.02-2.0 ng mL-1), low limit of detection (4.1 pg mL
      1) and good selectivity towards asulam determination, and has been successfully
      applied for the analysis of real environmental water samples with good accuracy
      of the recoveries ranged from 90% to 114%.

PMID- 29573622
TI  - Ageing opioid users' increased risk of methadone-specific death in the UK.
AB  - BACKGROUND: The first evidence that the hazard ratio (HR) for methadone-specific
      death rises more steeply with age-group than for all drug-related deaths (DRDs)
      came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to
      examine, for England, whether illicit opioid users' risk of methadone-specific
      death increases with age; and to pool age-related HRs for methadone-specific
      deaths with those for Scotland's methadone-prescription clients. METHODS: The
      setting is all services in England that provide publicly-funded, structured
      treatment for illicit opioid users, the methodology linkage of the English
      National Drug Treatment Monitoring System and mortality database, and key
      measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age
      group and gender, with proportional hazards adjustment for substances used,
      injecting status and periods in/out of treatment. RESULTS: Linkage was achieved
      for 129,979 adults receiving prescribing treatment modalities for opioid
      dependence during April 2005 to March 2009 and followed-up for 378,009 person
      years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys:
      irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7
      for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95%
      CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8
      21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to
      25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at
      <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at
      45+ years (95% CI: 2.99-4.70). CONCLUSION: International testing and explanation
      are needed of UK's sharp age-related increase in the risk of methadone-specific
      death. Clients should be alerted that their risk of methadone-specific death
      increases as they age.

PMID- 29573623
TI  - Social inequalities in quality of life in a cohort of women diagnosed with breast
      cancer in Barcelona (DAMA Cohort).
AB  - BACKGROUND: Breast cancer is a challenge for women's health-related quality of
      life (QoL), compromising their physical health and emotional well-being. QoL is
      equally distributed among different social groups. The aim of this study to
      analyze the impact of clinical characteristics and social determinants of health
      on the QoL of a cohort of women diagnosed and/or treated for breast cancer
      between 2003 and 2013 in one of the main hospitals in Barcelona's public health
      network. METHODS: We performed a descriptive cross-sectional study in a cohort of
      2235 women with various stages of breast cancer at different stages of their
      disease. Data were obtained using questionnaires QLQ-C30 and QLQ-BR23 from the
      European Organization for Research and Treatment of Cancer (EORTC), which include
      a set of functional and symptomatic scales. We conducted descriptive and
      bivariate analysis using the Chi-Square test and adjusted for relevant variables
      using logistic regression. The dependent variables were the functional scales of
      QoL and the independent variables were sociodemographic and clinical variables.
      RESULTS: We observed significant differences for most QoL functions. Women from
      the most disadvantaged class, those in social isolation, or those who had
      suffered relapses showed the poorest results for most of the function scales. In
      contrast, age had differential effects depending on the function studied.
      CONCLUSIONS: The QoL of women diagnosed with breast cancer is closely linked to
      both their social and economic status, and to their stage of disease progression.
      It is necessary to explore interventions that focus on the social determinants of
      health in order to mitigate their effects on breast cancer survivors' QoL.

PMID- 29573624
TI  - Ultrasonography of the airway to identify patients at risk for difficult tracheal
      intubation: Are we there yet?

PMID- 29573625
TI  - Metabolism profiling of nevadensin in vitro and in vivo by UHPLC-Q-TOF-MS/MS.
AB  - Nevadensin is major constituents of Lysionotus pauciflorus Maxim. (Chinese name:
      Shidiaolan), which has a variety of pharmacological effects such as anti
      mycobacterium tuberculosis activities, antitussive, anti-inflammatory and anti
      hypertensive. In this paper, we investigated the metabolism of nevadensin in
      vitro and in vivo. A strategy was firstly developed to identify the metabolites
      of nevadensin by using ultra-high performance liquid chromatography/quadrupole
      time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). An on-line data acquisition
      method a multiple mass defect filter (MMDF) combined with dynamic background
      subtraction (DBS) was developed to trace all probable metabolites. Furthermore,
      some assistant tools, such as key fragment ions (KFI), were employed for compound
      hunting and identification. Based on the proposed method, 23 metabolites were
      structurally characterized in vivo including 16 phase I and 7 phase II
      metabolites, and 12 metabolites were detected in vitro containing 10 phase I and
      2 phase II metabolites. The results indicated that oxidation, hydrolysis,
      demethylation, methylation, sulfate conjugation and glucuronide conjugation were
      main metabolic pathways of nevadensin. In a word, this study maybe can provide
      reference and valuable evidence for further investigation of the metabolic
      mechanism of nevadensin.

PMID- 29573626
TI  - Effects of combined oral contraception containing drospirenone on premenstrual
      exacerbation of Meniere's disease: Preliminary study.
AB  - OBJECTIVES: Meniere's disease is caused by an augmented endolymph pressure in the
      inner ear; symptoms are vertigo, fluctuating hearing loss and tinnitus.
      Exacerbations has been noted during premenstrual phase. The study aims to
      evaluate the effects of a 20 MUm Ethinylestradiol (EE) and 3 mg Drospirenone
      (DRSP) oral contraceptive (20 MUmEE/3mgDRSP) in continuous regimen, associated
      with rehabilitation therapy on Meniere's disease. STUDY DESIGN: This non
      randomized controlled study was performed from October 2015 to October 2017.
      Forty-two premenopausal women affected by MD with severe distress in the
      premenstrual phase were enrolled. Sixteen women constituted the study group
      (Group A), and twenty women constituted the control group (Group B). Group A
      underwent EE/DRSP therapy and rehabilitation and Group B underwent rehabilitation
      therapy alone. Stabilometry and the Dizziness Handicap Inventory questionnaire
      were used to measure vestibular function and distress related to the disease,
      respectively, at baseline (T0), 3 months (T1) and 6 months (T2). RESULTS: At T0,
      both groups had large, similar areas of stabilometric ellipses (p = NS) that
      reduced more in Group A than in Group B, at T1 and T2 (p < 0.001). High scores of
      the DHI (cut-off <=54) were observed at T0 in both groups (A 66.8 +/- 2.8 vs B
      65.5 +/- 3.6; p = NS). At T1, a gradual improvement in both groups was observed,
      manly in Group A (A 45.1 +/- 3.6 vs B 62.4 +/- 4.1; p < 0.001). At T2, the DHI
      scores were significantly lower in Group A (39.2 +/- 3.8) compared to Group B
      (68.8 +/- 3.6) (p < 0.001). CONCLUSIONS: DRSP could be effective in reducing the
      fluid overload typical of the premenstrual phase, improving symptoms of MD. The
      results support the efficacy of EE/DRSP usage associated with rehabilitation
      therapy on premenstrual exacerbation of MD.

PMID- 29573627
TI  - Intraoperative enhanced imaging for detection of endometriosis: A systematic
      review of the literature.
AB  - The diagnosis of peritoneal endometriosis during laparoscopy may be difficult due
      to the polymorphic aspects of the lesions. Enhanced imaging using contrast agents
      has potential to provide a better identification of peritoneal endometriosis. The
      aim of this systematic review is to provide an overview of the literature on what
      is known about the intraoperative laparoscopic visual enhancement of peritoneal
      endometriosis using contrast agents. A systematic review was done of studies
      about enhanced imaging during laparoscopy for endometriosis using contrast
      agents. Clinical studies which contained a description of imaging with a contrast
      agent and also reported visual findings of endometriosis during laparoscopy, were
      included. Nine suitable studies were identified. Intraoperative visualization of
      endometriosis was analyzed with or without histologic confirmation. Four studies
      evaluated 5-aminolevulinic acid-induced fluorescence (5-ALA), 1 study evaluated
      indigo carmine, 2 studies evaluated methylene blue (MB), 1 study evaluated
      indocyanine green (ICG) and 1 study evaluated so-called bloody peritoneal fluid
      painting. All studies, with a combined total of 171 included patients, showed
      potential of enhanced visibility of endometriosis using contrast agents. A
      combined total of 7 complications, all related to the use of 5-ALA, were
      reported. We conclude that the use of contrast-based enhanced imaging during
      laparoscopy is promising and that it can provide a better visualization of
      peritoneal endometriosis. However, based on the limited data no technique of
      preference can yet be identified.

PMID- 29573628
TI  - Removal of organic compounds from shale gas flowback water.
AB  - Ozonation, sorption to granular activated carbon and aerobic degradation were
      compared as potential treatment methods for removal of dissolved organic carbon
      (DOC) fractions and selected organic compounds from shale gas flowback water
      after pre-treatment in dissolved air flotation unit. Flowback water was
      characterised by high chemical oxygen demand and DOC. Low molecular weight (LMW)
      acids and neutral compounds were the most abundant organic fractions,
      corresponding to 47% and 35% of DOC respectively. Ozonation did not change
      distribution of organic carbon fractions and concentrations of detected
      individual organic compounds significantly. Sorption to activated carbon targeted
      removal of individual organic compounds with molecular weight >115 Da, whereas
      LMW compounds remained largely unaffected. Aerobic degradation was responsible
      for removal of LMW compounds and partial ammonium removal, whereas formation of
      intermediates with molecular weight of 200-350 Da was observed. Combination of
      aerobic degradation for LMW organics removal with adsorption to activated carbon
      for removal of non-biodegradable organics is proposed to be implemented between
      pre-treatment (dissolved air floatation) and desalination (thermal or membrane
      desalination) steps.

PMID- 29573629
TI  - Oxidation of steroid estrogens by peroxymonosulfate (PMS) and effect of bromide
      and chloride ions: Kinetics, products, and modeling.
AB  - Recently, in situ chemical oxidation (ISCO) using peroxymonosulfate (PMS) for
      environmental decontamination has received increasing interest. In this study,
      oxidation kinetics and products of four steroid estrogens (i.e., estrone, 17beta
      estradiol, estriol, and 17alpha-ethinylestradiol) by PMS under various conditions
      were investigated. PMS could fairly degrade steroid estrogens over the pH range
      of 7-10, and the degradation rate increased with the increase of solution pH.
      This pH-dependence was well described by parallel reactions between individual
      acid-base species of steroid estrogens (E and E-) and PMS (HSO5- and SO52-),
      where specific second-order rate constants for E- with HSO5- and SO52- were in
      the range of 2.11-5.58 M-1s-1 and 0.77-1.25 M-1s-1, respectively. Identification
      of oxidation products by liquid chromatography/electrospray ionization quadrupole
      time-of-flight mass spectrometer showed that PMS readily oxidized the phenolic
      group of steroid estrogens, leading to the generation of hydroxylated and ring
      opening products. The presence of bromide and chloride ions (Br- and Cl-) at
      environmentally relevant levels could greatly accelerate the degradation of
      steroid estrogens by PMS with the formation of halogenated aromatic products.
      This effect was quantitatively estimated by a kinetic model, where the formation
      of free bromine and chorine and their rapid electrophilic substitution with
      steroid estrogens were taken into consideration. Eco-toxicity of transformation
      products of 17alpha-ethinylestradiol by PMS treatment in the absence and presence
      of bromide and chloride was estimated by quantitative structure-activity
      relationship analysis using ECOSAR. These findings advance the understanding of
      ISCO using PMS.

PMID- 29573630
TI  - Removals of pesticides and pesticide transformation products during drinking
      water treatment processes and their impact on mutagen formation potential after
      chlorination.
AB  - Removal efficiencies of 28 pesticide transformation products (TPs) and 15 parent
      pesticides during steps in drinking water treatment (coagulation-sedimentation,
      activated carbon adsorption, and ozonation) were estimated via laboratory-scale
      batch experiments, and the mechanisms underlying the removal at each step were
      elucidated via regression analyses. The removal via powdered activated carbon
      (PAC) treatment was correlated positively with the log Kow at pH 7. The adjusted
      coefficient of determination (r2) increased when the energy level of the highest
      occupied molecular orbital (HOMO) was added as an explanatory variable, the
      suggestion being that adsorption onto PAC particles was largely governed by
      hydrophobic interactions. The residual error could be partly explained by pi-pi
      electron donor-acceptor interactions between the graphene surface of the PAC
      particles and the adsorbates. The removal via ozonation correlated positively
      with the energy level of the HOMO, probably because compounds with relatively
      high energy level HOMOs could more easily transfer an electron to the lowest
      unoccupied molecular orbital of ozone. Overall, the TPs tended to be more
      difficult to remove via PAC adsorption and ozonation than their parent
      pesticides. However, the TPs that were difficult to remove via PAC adsorption did
      not induce strong mutagenicity after chlorination, and the TPs that were
      associated with strong mutagenicity after chlorination could be removed via PAC
      adsorption. Therefore, PAC adsorption is hypothesized to be an effective method
      of treating drinking water to reduce the possibility of post-chlorination
      mutagenicity associated with both TPs and their parent pesticides.

PMID- 29573631
TI  - Emerging contaminants and nutrients synergistically affect the spread of class 1
      integron-integrase (intI1) and sul1 genes within stable streambed bacterial
      communities.
AB  - Wastewater effluents increase the nutrient load of receiving streams while
      introducing a myriad of anthropogenic chemical pollutants that challenge the
      resident aquatic (micro)biota. Disentangling the effects of both kind of
      stressors and their potential interaction on the dissemination of antibiotic
      resistance genes in bacterial communities requires highly controlled manipulative
      experiments. In this work, we investigated the effects of a combined regime of
      nutrients (at low, medium and high concentrations) and a mixture of emerging
      contaminants (ciprofloxacin, erythromycin, sulfamethoxazole, diclofenac, and
      methylparaben) on the bacterial composition, abundance and antibiotic resistance
      profile of biofilms grown in artificial streams. In particular, we investigated
      the effect of this combined stress on genes encoding resistance to ciprofloxacin
      (qnrS), erythromycin (ermB), sulfamethoxazole (sul1 and sul2) as well as the
      class 1 integron-integrase gene (intI1). Only genes conferring resistance to
      sulfonamides (sul1 and sul2) and intI1 gene were detected in all treatments
      during the study period. Besides, bacterial communities exposed to emerging
      contaminants showed higher copy numbers of sul1 and intI1 genes than those not
      exposed, whereas nutrient amendments did not affect their abundance. However,
      bacterial communities exposed to both emerging contaminants and a high nutrient
      concentration (1, 25 and 1 mg L-1 of phosphate, nitrate and ammonium,
      respectively) showed the highest increase on the abundance of sul1 and intI1
      genes thus suggesting a factors synergistic effect of both stressors. Since none
      of the treatments caused a significant change on the composition of bacterial
      communities, the enrichment of sul1 and intI1 genes within the community was
      caused by their dissemination under the combined pressure exerted by nutrients
      and emerging contaminants. To the best of our knowledge, this is the first study
      demonstrating the contribution of nutrients on the maintenance and spread of
      antibiotic resistance genes in streambed biofilms under controlled conditions.
      Our results also highlight that nutrients could enhance the effect of emerging
      contaminants on the dissemination of antibiotic resistance.

PMID- 29573633
TI  - Influence of laser therapy on the dynamic formation of extracellular matrix in
      standard second degree burns treated with bacterial cellulose membrane.
AB  - The present study aims to assess the influence of Aluminum-Gallium-Indium
      Phosphide laser (AlGaInP laser, lambda = 660 nm), whether or not in association
      with the application of a membrane of bacterial cellulose (NexfillTM), during
      recovery from induced second-degree burns at the dorsum of Wistar rats. (Rattus
      norvegicus, Wistar). Forty-eight animals have been distributed into four groups:
      Control (burns remained untreated), Group I (laser-treated), Group II (treated
      with Nexfill), and Group III (laser + NexfillTM). In addition to a morphological
      analysis, immunohistochemical analysis has been performed for type I collagen,
      type III collagen, fibronectin, and laminin. The Fisher's Test was used to assess
      differences among groups (p < 0,05). A larger amount of collagen type III was
      observed in Control, Group II and Group III when compared with Group I (p <
      0,05). Group I and Group III have shown a greater collagen deposition when
      compared with Group II (p < 0,05), but the amount of collagen was similar in
      Group I, Group III, and Control. Group III has shown larger fibronectin amounts
      in comparison with Group II (p < 0,05). As regards laminin, Group I has shown a
      predominant discontinuity pattern on the basal lamina in comparison with Control,
      Group II, and Group III (p < 0,05). It is concluded that in this current study
      the laser when used alone (Group I) hasn't influenced collagen deposition neither
      has it acted on fiber pattern (fibril and/or reticular). Moreover, laser
      application hasn't accelerated the repair of wounds caused by inflicted second
      degree burns.

PMID- 29573632
TI  - Assessing the origin of bacteria in tap water and distribution system in an
      unchlorinated drinking water system by SourceTracker using microbial community
      fingerprints.
AB  - The general consensus is that the abundance of tap water bacteria is greatly
      influenced by water purification and distribution. Those bacteria that are
      released from biofilm in the distribution system are especially considered as the
      major potential risk for drinking water bio-safety. For the first time, this full
      scale study has captured and identified the proportional contribution of the
      source water, treated water, and distribution system in shaping the tap water
      bacterial community based on their microbial community fingerprints using the
      Bayesian "SourceTracker" method. The bacterial community profiles and diversity
      analyses illustrated that the water purification process shaped the community of
      planktonic and suspended particle-associated bacteria in treated water. The
      bacterial communities associated with suspended particles, loose deposits, and
      biofilm were similar to each other, while the community of tap water planktonic
      bacteria varied across different locations in distribution system. The microbial
      source tracking results showed that there was not a detectable contribution of
      source water to bacterial community in the tap water and distribution system. The
      planktonic bacteria in the treated water was the major contributor to planktonic
      bacteria in the tap water (17.7-54.1%). The particle-associated bacterial
      community in the treated water seeded the bacterial community associated with
      loose deposits (24.9-32.7%) and biofilm (37.8-43.8%) in the distribution system.
      In return, the loose deposits and biofilm showed a significant influence on tap
      water planktonic and particle-associated bacteria, which were location dependent
      and influenced by hydraulic changes. This was revealed by the increased
      contribution of loose deposits to tap water planktonic bacteria (from 2.5% to
      38.0%) and an increased contribution of biofilm to tap water particle-associated
      bacteria (from 5.9% to 19.7%) caused by possible hydraulic disturbance from
      proximal to distal regions. Therefore, our findings indicate that the tap water
      bacteria could possibly be managed by selecting and operating the purification
      process properly and cleaning the distribution system effectively.

PMID- 29573634
TI  - Human serum albumin binding to the biologically active labdane diterpene
      "leoheterin": Spectroscopic and in silico analysis.
AB  - Labdane diterpenes are important substances due to their remarkable biological
      activities such as, antibacterial, antiprotozoal, antifungal and cytostatic and
      cytotoxic effects against human cancer cells. We have isolated a labdane
      diterpene named "leoheterin" from the aerial parts of the Otostegia fruticosa
      Forssk (Briq) obtained from south west Arabian mountains of Saudi Arabia. The
      isolated compound was characterized by 1HNMR, 13CNMR, IR and UV-visible
      spectroscopies. Due to the pharmaceutical importance of this class of compounds
      we have studied the interaction of HSA with leoheterin by using several
      spectroscopic methods. The change in the UV spectrum of HSA in presence of
      leoheterin gives a primary idea about the interaction between them. Congruently,
      leoheterin quenches the fluorescence of HSA with a prominent blue shift of 5 nm,
      reminiscent of involvement of hydrophobic interactions. There was 1:1 binding
      between leoheterin and albumin which was taken place via static quenching
      mechanism. From CD it was revealed that leoheterin induces the secondary
      structure of HSA which is further supported by 3-d fluorescence measurements
      which shows a decrease in the size of the HSA-leoheterin complex as compared to
      the HSA alone. Molecular docking simulations presented that among the first three
      conformers, which have been arranged according to the least binding energies and
      are also in good corroboration with the free energies of binding obtained
      experimentally, the first two conformers shown the binding in hemin binding site
      of subdomain IB while in third conformer the binding site was near to the drug
      binding site 1 located in subdomain IIA. All conformers exhibited the involvement
      of hydrogen bonding as well as hydrophobic interactions.

PMID- 29573635
TI  - Fabrication of multi-functional porous microspheres in a modular fashion for the
      detection, adsorption, and removal of pollutants in wastewater.
AB  - Water pollution control has become significant challenges in recent years because
      of their extensive species diversity. It is critical to developing general
      purpose materials for environmental rehabilitation. In this paper, a novel module
      assembly method is developed to prepare multi-functional materials for treating
      pollutants in water. Building blocks are porous nanoparticles with a different
      function. Microspheres (MS) with a diameter of 90 MUm are prepared and have a
      coefficient of variation of 6.8%. The modular fashion of self-assembly process in
      a microfluidic chip is the crucial factor in fabricating the multifunction
      material. The assembled microspheres with different building modules still have a
      specific surface area larger than 400 m2 g-1, and exhibit excellent performance
      in adsorbing various pollutants in water, such as heavy metal ions and organic
      dyes. The adsorption capacities of them to Hg2+ and orange II reach 150 mg g-1
      and 333 mg g-1, respectively. The integrated fluorescence probes in microspheres
      can detect low concentration (9.8 ppb) of Hg2+. Microspheres integrated with
      Fe3O4 nanoparticles have a magnetic susceptibility of 6.01 emu g-1 and can be
      easily removed from wastewater by applying an external magnetic. Due to the
      stability of inorganic building blocks, each function in the assembled system is
      well performed, and multi-functional "All-in-One" materials can be easily
      fabricated.

PMID- 29573636
TI  - POH1 Knockdown Induces Cancer Cell Apoptosis via p53 and Bim.
AB  - The ubiquitin-proteasome system is implicated in cell apoptosis that is
      frequently dysregulated in human cancers. POH1/rpn11/PSMD14, as a part of the 19S
      proteasomal subunit, contributes to the progression of malignancy, but its role
      in apoptosis remains unclear. Here, we showed that POH1 expression was increased
      and associated with poor outcomes in three independent cohorts of patients with
      hepatocellular carcinoma (HCC), esophageal cancer (EC), and colorectal cancer
      (CRC). The knockdown of POH1 significantly inhibited tumor cell proliferation and
      induced apoptosis mediated by the mitochondrial pathway in vitro. Intratumoral
      injection of POH1 small interfering RNA (siRNA) significantly reduced the
      progression of tumor growth and induced apoptosis in vivo. Furthermore, p53 or
      Bim siRNA markedly attenuated the apoptosis induced by POH1 depletion. POH1
      depletion resulted in cell apoptosis by increasing the stability of p53 and Bim
      and inhibiting their ubiquitination. Overall, POH1 knockdown induced cell
      apoptosis through increased expression of p53 and Bim via enhanced protein
      stability and attenuated degradation. Thus, POH1 may serve as a potential
      prognostic marker and therapeutic target in human cancers.

PMID- 29573637
TI  - Development of a New Monochrome Multiplex qPCR Method for Relative Telomere
      Length Measurement in Cancer.
AB  - Excess telomere shortening has been observed in most cancer cells. The telomere
      quantitative polymerase chain reaction (qPCR) assay has become an important tool
      for epidemiological studies examining the effects of aging, stress, and other
      factors on the length of telomeres. Current telomere qPCR methods analyze the
      relative length of telomeres by amplifying telomere sequence products and
      normalizing with single-copy gene products. However, the current telomere qPCR
      does not always reflect absolute telomere length in cancer DNA. Because of
      genomic instability in cancer cells, we hypothesized that the use of single-copy
      genes (scg) is less accurate for normalizing data in cancer DNA and that new
      primer sets are required to better represent relative telomere length in cancer
      DNA. We first confirmed that cancer cells had a different copy ratio among
      different scg, implying that DNA is aneuploid. By using the new primer sets that
      amplify multiple-copy sequences (mcs) throughout the genome, the telomere qPCR
      results showed that the mcs primers were interchangeable with the scg primers as
      reference primers in normal DNA. By comparing results from the traditional
      southern blotting method (as kilobases) and results from monochrome multiplex
      qPCR using the mcs primers (as T/M ratios), we verified that the T/M ratio is
      highly correlated with absolute telomere length from the southern blot analysis.
      Together, the mcs primers were able to represent the telomere lengths accurately
      in cancer DNA samples. These results would allow for analyses of telomeres within
      cancerous DNA and the development of new, less invasive diagnostic tools for
      cancer.

PMID- 29573638
TI  - N-linoleoylamino acids as chiral probes of substrate binding by soybean
      lipoxygenase-1.
AB  - Lipoxygenases catalyze the oxygenation of polyunsaturated fatty acids and their
      derivatives to produce conjugated diene hydroperoxides. Soybean lipoxygenase-1
      (SBLO-1) has been the subject of intensive structural and mechanistic study, but
      the manner in which this enzyme binds substrates is uncertain. Previous studies
      suggest that the fatty acyl group of the substrate binds in an internal cavity
      near the catalytic iron with the polar end at the surface of the protein or
      perhaps external to the protein. To test this model, we have investigated two
      pairs of enantiomeric N-linoleoylamino acids as substrates for SBLO-1. If the
      amino acid moiety binds external to the protein, the kinetics and product
      distribution should show little or no sensitivity to the stereochemical
      configuration of the amino acid moiety. Consistent with this expectation, N
      linoleoyl-l-valine (LLV) and N-linoleoyl-d-valine (LDV) are both good substrates
      with kcat/Km values that are equal within error and about 40% higher than kcat/Km
      for linoleic acid. Experiments with N-linoleoyl-l-tryptophan (LLT) and N
      linoleoyl-d-tryptophan (LDT) were complicated by the low critical micelle
      concentrations (CMC = 6-8 MUM) of these substances. Below the CMC, LDT is a
      better substrate by a factor of 2.7. The rates of oxygenation of LDT and LLT
      continue to rise above the CMC, with modest stereoselectivity in favor of the d
      enantiomer. With all of the substrates tested, the major product is the 13(S)
      hydroperoxide, and the distribution of minor products is not appreciably affected
      by the configuration of the amino acid moiety. The absence of stereoselectivity
      with LLV and LDV, the modest magnitude of the stereoselectivity with LLT and LDT,
      and the ability micellar forms of LLT and LDT to increase the concentration of
      available substrate are all consistent with the hypothesis that the amino acid
      moiety binds largely external to SBLO-1 and interacts with it only weakly.

PMID- 29573639
TI  - Integrin alphavbeta6 Promotes Lung Cancer Proliferation and Metastasis through
      Upregulation of IL-8-Mediated MAPK/ERK Signaling.
AB  - Lung cancer is notorious for high morbidity and mortality around the world.
      Interleukin (IL)-8, a proinflammatory chemokine with tumorigenic and
      proangiogenic effects, promotes lung cancer cells growth and migration and
      contributes to cell aggressive phenotypes. Integrin alphavbeta6 is a receptor of
      transmembrane heterodimeric cell surface adhesion, and its overexpression
      correlates with poor survival from non-small cell lung cancer. However, the cross
      talk between alphavbeta6 and IL-8 in lung cancer has not been characterized so
      far. Herein, human lung cancer samples were analyzed, and it revealed that the
      immunohistochemical and mRNA expression of integrin alphavbeta6 was significantly
      correlated with the expression of IL-8. Furthermore, in vitro, integrin
      alphavbeta6 increased cell proliferation, migration, and invasion by impairing
      the expressions of MMP-2 and MMP-9 and inhibited cell apoptosis in human lung
      cancer cells A549 and H460. In addition, integrin alphavbeta6 upregulated IL-8
      expression through activating MAPK/ERK signaling. The in vivo experiment showed
      that integrin alphavbeta6 promoted tumor growth in xenograft model mice by
      accelerating tumor volume and reducing apoptosis. Meanwhile, lung metastasis
      model experiment suggested that integrin alphavbeta6 stimulated tumor metastasis
      with the increase of lung/total weight and tumor nodules. Simultaneously,
      integrin alphavbeta6 upregulated IL-8 expression detected by both Western blots
      and immunohistochemistry, along with the activation of MAPK/ERK signaling.
      Overall, these data suggested that, in vitro and in vivo, integrin alphavbeta6
      promoted lung cancer proliferation and metastasis, at least in part, through
      upregulation of IL-8-mediated MAPK/ERK signaling. Thus, the inhibition of
      integrin alphavbeta6 and IL-8 may be the key for the treatment of lung cancer.

PMID- 29573640
TI  - Tipping microtubule dynamics, one protofilament at a time.
AB  - Microtubules are polymeric tubes that switch between phases of growth and
      shortening, and this property is essential to drive key cellular processes.
      Microtubules are composed of protofilaments formed by longitudinally arranged
      tubulin dimers. Microtubule dynamics can be affected by structural perturbations
      at the plus end, such as end tapering, and targeting only a small subset of
      protofilaments can alter the dynamics of the whole microtubule. Microtubule
      lattice plasticity, including compaction along the longitudinal axis upon GTP
      hydrolysis and tubulin dimer loss and reinsertion along microtubule shafts can
      also affect microtubule dynamics or mechanics. Microtubule behaviour can be fine
      tuned by post-translational modifications and tubulin isotypes, which together
      support the diversity of microtubule functions within and across various cell
      types or cell cycle and developmental stages.

PMID- 29573641
TI  - Impact sites representing potential bruising locations associated with bed falls
      in children.
AB  - Bruising can occur as a result of accidental or abusive trauma in children.
      Bruises are an early sign of child abuse and their locations on the body can be
      an effective delineator of abusive trauma. Since falls are often reported as
      false histories in abuse, the ability to predict potential bruising locations in
      falls could be valuable when attempting to differentiate between abuse and
      accident. In our study we used an anthropomorphic test device (ATD), a surrogate
      representing a 12 month old child, adapted with a custom developed force sensing
      skin to predict potential bruising locations during simulated bed falls. The
      sensing skin is made of custom resistive force sensors integrated into a
      conformable skin, adapted to fit the contours of the ATD. The sensing skin
      measured and displayed recorded force data on a computerized body image mapping
      system when sensors were activated. Simulated bed fall experiments were performed
      from two initial positions (FF - facing forward and FR - facing rearward) and two
      fall heights of 61cm (24 in) and 91cm (36 in) onto a padded carpet impact
      surface. Findings indicated potential bruising primarily in two planes of the ATD
      body. The majority of contact regions and greater forces were recorded in one
      plane, with fewer regions of contact and decreased force exhibited in an
      adjoining second plane. Additionally, no contact was recorded in the two planes
      opposite the impact planes. Differences in contact regions were observed for
      varying heights and initial position. Limitations of ATD biofidelity and soft
      tissue properties must be considered when interpreting these findings.

PMID- 29573642
TI  - Analytical and transfer characteristics of a fluorescent detection spray:
      Implications for subvisible and nanotrace particle transfers.
AB  - Fluorescent detection sprays are applied to objects to elucidate evidence of
      contact. Billed as an invisible powder, evidence of contact between objects may
      be visualized through illumination by ultra-violet light, which causes the
      fluorescent tracer to luminesce. While the presence of the fluorescent powder on
      a suspect or object is often used as evidence of direct contact, the fine nature
      of the powder, which is comprised of sub-visible particles that are generally
      less than 10 MUm in diameter, lends itself to higher-order transfers that do not
      necessarily involve the original object. Due to the small particle size and light
      yellow color, the particles are generally invisible to the unaided eye in white
      light. This increases the opportunity for unwanted or unanticipated transfers
      (i.e., contamination). This article provides a microanalytical characterization
      of a common fluorescent tracer and the approaches by which this powder (or
      analogous powders) may be applied, detected, and specifically identified in
      quantities that range from major to trace. This research illustrates the ease of
      higher order cross-transfers (up to the 10th order) and the considerations
      necessary to maximize the evidentiary value of sub-visible particles and
      nanotraces, while minimizing the chances of cross-contamination.

PMID- 29573643
TI  - Profiles of internalizing and externalizing symptoms associated with bullying
      victimization.
AB  - This study identified profiles of internalizing (anxiety and depression) and
      externalizing (delinquency and violence against peers) symptoms among bullying
      victims and examined associations between bullying victimization characteristics
      and profile membership. The sample consisted of 1196 bullying victims in grades 8
      10 (Mage = 14.4, SD = 1.01) who participated in The Context Study in three North
      Carolina counties in Fall 2003. Five profiles were identified using latent
      profile analysis: an asymptomatic profile and four profiles capturing
      combinations of internalizing and externalizing symptoms. Associations between
      bullying characteristics and membership in symptom profiles were tested using
      multinomial logistic regression. More frequent victimization increased odds of
      membership in the two high internalizing profiles compared to the asymptomatic
      profile. Across all multinomial logistic regression models, when the high
      internalizing, high externalizing profile was the reference category, adolescents
      who received any type of bullying (direct, indirect, or dual) were more likely to
      be in this category than any others.

PMID- 29573644
TI  - Intimacy development in late adolescence: Longitudinal associations with
      perceived parental autonomy support and adolescents' self-worth.
AB  - The present longitudinal study tested for the role of perceived parental autonomy
      support and late adolescents' self-worth in their intimacy development. A sample
      of 497 Belgian late adolescents (Mage = 17.9, 43.5% girls) participated in this
      two-wave study. Results indicated that perceived autonomy-supportive parenting
      did not relate significantly to change in adolescents' experienced intimacy (in
      terms of closeness and mutuality), but was associated with a decrease in
      unmitigated agency (an excessive focus on the self) and unmitigated communion (an
      excessive focus on the other) across time. Adolescents' self-worth predicted an
      increase in experienced intimacy and a decrease in unmitigated agency and
      communion, and the initial level of experienced intimacy predicted an increase in
      self-worth. Finally, results suggested that adolescents' self-worth may mediate
      some of the longitudinal relations between perceived parental autonomy-support
      and adolescents' intimate functioning. No evidence was found for moderation by
      romantic involvement, gender or age.

PMID- 29573645
TI  - Phonetic radicals, not phonological coding systems, support orthographic learning
      via self-teaching in Chinese.
AB  - According to the self-teaching hypothesis (Share, 1995), phonological decoding is
      fundamental to acquiring orthographic representations of novel written words.
      However, phonological decoding is not straightforward in non-alphabetic scripts
      such as Chinese, where words are presented as characters. Here, we present the
      first study investigating the role of phonological decoding in orthographic
      learning in Chinese. We examined two possible types of phonological decoding: the
      use of phonetic radicals, an internal phonological aid, andthe use of Zhuyin, an
      external phonological coding system. Seventy-three Grade 2 children were taught
      the pronunciations and meanings of twelve novel compound characters over four
      days. They were then exposed to the written characters in short stories, and were
      assessed on their reading accuracy and on their subsequent orthographic learning
      via orthographic choice and spelling tasks. The novel characters were assigned
      three different types of pronunciation in relation to its phonetic radical - (1)
      a pronunciation that is identical to the phonetic radical in isolation; (2) a
      common alternative pronunciation associated with the phonetic radical when it
      appears in other characters; and (3) a pronunciation that is unrelated to the
      phonetic radical. The presence of Zhuyin was also manipulated. The children read
      the novel characters more accurately when phonological cues from the phonetic
      radicals were available and in the presence of Zhuyin. However, only the phonetic
      radicals facilitated orthographic learning. The findings provide the first
      empirical evidence of orthographic learning via self-teaching in Chinese, and
      reveal how phonological decoding functions to support learning in non-alphabetic
      writing systems.

PMID- 29573646
TI  - Evaluation of interleukin-1beta level and oxidative status in gingival crevicular
      fluid during rapid maxillary expansion.
AB  - OBJECTIVES: The levels of interleukin-1beta (IL-1beta), nitric oxide (NO), total
      antioxidant capacity (TAC), and total oxidant status (TOS) in gingival crevicular
      fluid (GCF) were determined during rapid maxillary expansion (RME) treatment.
      MATERIALS AND METHODS: Fourteen patients (10-13 years old) were included. A
      modified hyrax appliance was used for the treatment. After periodontal parameters
      were recorded, GCF was collected from the first molars at each observation
      [T1:baseline:14 days after periodontal prophylaxis and instructions; T2:1 day
      later hyrax inserted, at passive position; T3:1 week later; after the first
      activation; T4:after 2 * 1/4 activation; T5:after 7 * 1/4 activation; T6:after 14
      * 1/4 activation; T7:retention period on the 1 st month; and T8:retention period
      on the 3rd month]. RESULTS: Although the levels of IL1-beta, NO, and PD increased
      significantly from T1 to T2, the GI, BOP%, and PI remained unchanged throughout
      treatment. GCF volume at buccal and palatal surfaces increased significantly from
      T1 to T4, T6, T7, and T8. The parameters in GCF and TAC levels were not only
      higher at palatal side in comparison with buccal, but also TOS levels increased
      at both buccal and palatal sides. CONCLUSIONS: In this study, the differences of
      oxidative status and IL-1beta levels during RME treatment could be attributable
      to orthopedic effect of the heavy forces on maxilla and minimal orthodontic
      forces on teeth applied by the RME apparatus.

PMID- 29573647
TI  - Oral spray containing plant-derived compounds is effective against common oral
      pathogens.
AB  - OBJECTIVES: Plant-derived compounds are a good source of therapeutic agents and
      inhibitors of inflammatory process. Dental caries, periodontal diseases and
      candidiasis are common oral infections caused by virulent biofilms. The
      objectives of this study were to develop oral spray containing plant-derived
      compounds; alpha-mangostin (alpha-MG) and/or lawsone methyl ether (2-methoxy-1,4
      naphthoquinone) (LME) and determine its antimicrobial, anti-biofilm, and anti
      inflammatory activities. DESIGN: Oral spray formulations were prepared containing
      alpha-MG (5 mg/ml) and/or LME (250 MUg/ml). Antimicrobial activity against
      Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis and anti
      biofilm formation activities were determined as well as cytotoxicity and anti
      inflammatory effects. RESULTS: The oral spray demonstrated antimicrobial activity
      against all three of the oral pathogens tested with stronger effects on C.
      albicans and S. mutans than P. gingivalis. The formulation containing alpha-MG
      (2.5 mg/ml) and LME (125 ug/ml) reduced growth of the microorganisms about 1-2
      Log CFU/ml at 1-3 h and the killing effects were complete at 24 h. Based on
      biofilm assay, the oral spray containing both alpha-MG and LME showed greater
      inhibitory effects than those with alpha-MG or LME. In addition, the oral spray
      containing both alpha-MG and LME demonstrated more inhibition of nitric oxide
      production than alpha-MG alone. All the formulations were safe and demonstrated
      greater anti-inflammatory activity at lower concentration (<6.25 MUg/ml) than at
      a higher concentration. CONCLUSION: Oral spray containing alpha-MG and/or LME is
      effective against common oral pathogens without significant cytotoxicity. Thus,
      it has the potential to prevent the infections and may serve as adjunctive
      treatment to conventional therapy.

PMID- 29573648
TI  - Atomoxetine for amphetamine-type stimulant dependence during buprenorphine
      treatment: A randomized controlled trial.
AB  - BACKGROUND: Amphetamine type stimulants (ATS) use is highly prevalent and
      frequently co-occurs with opioid dependence in Malaysia and Asian countries. No
      medications have established efficacy for treating ATS use disorder. This study
      evaluated the safety, tolerability, and potential efficacy of atomoxetine for
      treating ATS use disorder. METHODS: Participants with opioid and ATS dependence
      (N = 69) were enrolled in a pilot, double-blind, placebo-controlled randomized
      clinical trial; all received buprenorphine/naloxone and behavioral counseling and
      were randomized to atomoxetine 80 mg daily (n = 33) or placebo (n = 33). The
      effect size of the between-group difference on the primary outcome, proportion of
      ATS-negative urine tests, was estimated using Cohen's d for the intention-to
      treat (ITT) sample and for higher adherence subsample (>=60 days of atomoxetine
      or placebo ingestion). RESULTS: Participants were all male with mean (SD) age
      39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in
      atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67
      (0.53-0.81, d = 0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78,
      d = 0.56) in the higher adherence subsample. The proportion of days abstinent
      from ATS increased from baseline in both groups (p < 0.001) and did not differ
      significantly between atomoxetine- and placebo-treated participants (p = 0.42).
      Depressive symptoms were reduced from baseline in both groups (p < 0.02) with a
      greater reduction for atomoxetine- than placebo-treated participants (p < 0.02).
      There were no serious adverse events or adverse events leading to medication
      discontinuation. CONCLUSIONS: The findings support clinical tolerability and
      safety and suggest potential efficacy of atomoxetine for treating ATS use
      disorder in this population.

PMID- 29573649
TI  - Perceptions and practices addressing diversion among US buprenorphine
      prescribers.
AB  - BACKGROUND: While there has been a dramatic increase in prescribing of
      buprenorphine for the treatment of opioid use disorder in the US, little is known
      about prescribers' attitudes and practices regarding buprenorphine diversion and
      how they relate to prescriber characteristics. METHODS: A national random sample
      of buprenorphine prescribers (N = 1174) completed surveys from July 2014 to
      January 2017. Analyses examined relationships between prescriber and practice
      characteristics and prescriber perceptions and approaches regarding diversion.
      RESULTS: Among this sample of buprenorphine prescribers, 79.0% (N = 898) reported
      assessing all patients for risk of buprenorphine diversion and misuse. A third of
      prescribers described diversion as a significant or very significant concern in
      their community. The majority of prescribers reported seeing patients on average
      at least every other week during the first 60 days of treatment, and the majority
      reported testing urine for buprenorphine to assess for diversion. Perceptions of
      diversion being a greater problem in their community (AOR 1.212, 95% CI 1.073
      1.369) and use of medication counts (AOR 1.006, 95% CI 1.003-1.009) were
      associated with increased likelihood of terminating patients when diversion was
      suspected, while having expertise in addiction (AOR 0.526, 95% CI 0.406-0.682) or
      psychiatry (AOR 0.714, 95% CI 0.558-0.914) were associated with decreased odds of
      terminating treatment for suspected diversion. CONCLUSIONS: Buprenorphine
      prescribers report diversion is an important issue, and most prescribers report
      that they assess patients for diversion, though specific practices differ based
      on prescriber and practice characteristics.

PMID- 29573651
TI  - Near infrared-emitting persistent luminescent nanoparticles for Hepatocellular
      Carcinoma imaging and luminescence-guided surgery.
AB  - Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, is
      increasing nowadays and poses a serious threat to human health. However, if
      treated effectively and timely, it is clinically manageable or curable.
      Therefore, accurate detection and complete surgical resection remain priorities
      for HCC with a high potential of improving both survival and quality of life.
      Lacking of real-time guide technology, traditional surgery are usually relied on
      the subjective experience of surgeon, which have the limitation of high
      sensitivity detection tumor. Here, we developed a contrast agent, ZnGa2O4Cr0.004
      (ZGC), used for guided surgery during operation to accurate delineation of HCC.
      ZGC showed excellent long-lasting afterglow properties that lasted for hours,
      which can aid in real-time guided surgery. Meanwhile, ZGC display high spatial
      resolution and deep penetration during pre-operation for diagnostic computed
      tomography (CT). Interestingly, we observed reverse imaging in the tumor region,
      known as a "dark hole", which further improves the contrast for surgery. This new
      multi-modality nanoparticle has great potential for accurate liver cancer imaging
      and resection guidance.

PMID- 29573650
TI  - Does exposure to parental substance use disorders increase offspring risk for a
      substance use disorder? A longitudinal follow-up study into young adulthood.
AB  - OBJECTIVE: The main aim of this study was to examine the risk of exposure to
      parental substance use disorders (SUD; alcohol or drug abuse or dependence) on
      the risk for SUD in offspring with and without attention deficit hyperactivity
      disorder (ADHD) followed into young adult years. METHODS: Subjects were derived
      from two longitudinal case-control studies of probands of both sexes, 6-17 years,
      with and without DSM-III-R ADHD and their parents. Probands were followed for ten
      years into young adulthood. Probands with a parental history of non-nicotine SUD
      were included in this analysis. Exposure to SUD was determined by active non
      nicotine parental SUD while the parent was living with their child after birth.
      Cox proportional hazard models were used to calculate the risk of non-nicotine
      SUD in offspring. RESULTS: 171 of the 404 probands reassessed at ten-year follow
      up had a family history of parental SUD. 102 probands were exposed to active
      parental SUD. The average age of our sample was 22.2 +/- 3.5 years old. Exposure
      to maternal but not paternal SUD increased offspring risk for an alcohol use
      disorder in young adulthood independently of ADHD status (OR: 2.7; 95% CI: 1.1,
      6.9; p = 0.04). CONCLUSION: Exposure to maternal SUD increases the risk for an
      alcohol use disorder in offspring ten years later in young adult years
      irrespective of ADHD status.

PMID- 29573652
TI  - The impact of emotional labor on the severity of PTSD symptoms in firefighters.
AB  - BACKGROUND: Despite attempts to identify predictors for posttraumatic stress
      disorder (PTSD) in firefighters, it is still uncertain whether occupational
      stress factors impact PTSD symptoms. Given the emotionally taxing job environment
      of firefighters, this population has been known to suffer from emotional labor.
      In this study, we investigated whether and how emotional labor, one of the
      occupational stress factors, influences the severity of PTSD symptoms in
      firefighters. METHODS: A total of 7151 Korean firefighters (age range 21-60
      years, 6484 (90.7%) male participants) were included for analysis. PTSD symptoms
      were assessed using the PTSD Checklist-Civilian Version, and the demands of
      emotional labor and emotional damage were measured using the Korean Emotional
      Labor Scale. Hierarchical multivariate regression was performed. RESULTS:
      Hierarchical multivariate regression showed that a 2-way interaction between the
      presence of recent trauma and emotional damage was significantly associated with
      the severity of PTSD symptoms, even after adjusting for demographic factors, job
      related factors, and perceived stress. The independent main effects of emotional
      labor were not significantly associated with PTSD symptoms. CONCLUSION: These
      findings suggest that emotional labor can be a risk factor that makes
      firefighters vulnerable to PTSD symptoms by modulating the effect of traumatic
      experiences on PTSD symptoms.

PMID- 29573654
TI  - Pneumonia risk of people living close to goat and poultry farms - Taking GPS
      derived mobility patterns into account.
AB  - We previously observed an increased incidence of pneumonia in persons living near
      goat and poultry farms, using animal presence around the home to define exposure.
      However, it is unclear to what extent individual mobility and time spent outdoors
      close to home contributes to this increased risk. Therefore, the aim of the
      current study was to investigate the role of mobility patterns and time spent
      outdoors in the vicinity of goat or poultry farms in relation to pneumonia risk.
      In a rural Dutch cohort, 941 members logged their mobility using GPS trackers for
      7 days. Pneumonia was diagnosed in 83 subjects (participants reported that
      pneumonia had been diagnosed by a medical doctor, or recorded in EMR from general
      practitioners, 2011-2014). We used logistic regression to evaluate pneumonia-risk
      by presence of goat farms within 500 and 1000 m around the home and around GPS
      tracks (only non-motorised mobility), also we evaluated whether more time spent
      outdoors increased pneumonia-risks. We observed a clearly increased risk of
      pneumonia among people living in close proximity to goat farms, ORs increased
      with closer distances of homes to farms (500 m: 6.2 (95% CI 2.2-16.5) 1000 m: 2.5
      (1.4-4.3)) The risk increased for individuals who spent more time outdoors close
      to home, but only if homes were close to goat farms (within 500 m and often
      outdoors: 12.7 (3.6-45.4) less often: 2.0 (0.3-9.2), no goat farms and often
      outdoors: 1.0 (0.6-1.6)). For poultry we found no increased risks. Pneumonia
      risks increased when people lived near goat farms, especially when they spent
      more time outdoors, mobility does not seem to add to these risks.

PMID- 29573653
TI  - Maternal polymorphisms in glutathione-related genes are associated with maternal
      mercury concentrations and early child neurodevelopment in a population with a
      fish-rich diet.
AB  - INTRODUCTION: Glutathione (GSH) pathways play a key role the metabolism and
      elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that
      maternal genetic variation linked to GSH pathways could influence MeHg
      concentrations in pregnant mothers and children and thereby also affect early
      life development. METHODS: The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and
      GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective
      study of the Seychellois population with a diet rich in fish. Genotypes were
      analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord
      blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and
      PDI assessed by Bayley Scales of Infant Development at 20 months). We also
      examined whether genotypes modified the association between Hg exposure and
      developmental outcomes. RESULTS: GCLC rs761142 TT homozygotes showed
      statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73
      and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM
      rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G +
      T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1
      rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or
      cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a
      lower MDI among children (beta = -1.48, p = 0.048). We also observed some
      interactions: increasing Hg in maternal and cord blood was associated with lower
      PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated
      with lower MDI among GSTP1 rs1695 GG carriers. CONCLUSIONS: Maternal genetic
      variation in genes involved in GSH synthesis is statistically associated with Hg
      concentrations in maternal hair, but not in maternal or fetal blood. We observed
      interactions that suggest maternal GSH genetics may modify associations between
      MeHg exposure and neurodevelopmental outcomes.

PMID- 29573655
TI  - Drivers of contaminant levels in surface water of China during 2000-2030:
      Relative importance for illustrative home and personal care product chemicals.
AB  - Water pollution are among the most critical problems in China and emerging
      contaminants in surface water have attracted rising attentions in recent years.
      There is great interest in China's future environmental quality as the national
      government has committed to a major action plan to improve surface water quality.
      This study presents methodologies to rank the importance of socioeconomic and
      environmental drivers to the chemical concentration in surface water during 2000
      2030. A case study is conducted on triclosan, a home and personal care product
      (HPCP) ingredient. Different economic and discharge flow scenarios are
      considered. Urbanization and wastewater treatment connection rates in rural and
      urban areas are collected or projected for 2000-2030 for counties across China.
      The estimated usage increases from ca. 86 to 340 t. However, emissions decreases
      from 76 to 52 t during 2000-2030 under a modelled Organisation for Economic Co
      operation (OECD) economic scenario because of the urbanization, migration and
      development of wastewater treatment plants/facilities (WWTPs). The estimated
      national median concentration of triclosan ranges 1.5-8.2 ng/L during 2000-2030
      for different scenarios. It peaks in 2009 under the OECD and three of the
      Intergovernmental Panel on Climate Change (IPCC), A2, B1 and B2 economic
      scenarios, but in 2025 under A1 economic scenario. Population distribution and
      surface water discharge flow rates are ranked as the top two drivers to triclosan
      levels in surface water over the 30 years. The development of urban WWTPs was the
      most important driver during 2000-2010 and the development of rural works is
      projected to be the most important in 2011-2030. Projections suggest discharges
      of ingredients in HPCPs - controlled by economic growth - should be balanced by
      the major expenditure programme on wastewater treatment in China.

PMID- 29573656
TI  - Beck Self-Esteem Scale-Short Form: Development and psychometric evaluation of a
      scale for the assessment of self-concept in schizophrenia.
AB  - A requisite step for testing cognitive theories regarding the role of self
      concept in schizophrenia is the development of measures that follow a cognitive
      conceptualization and better capture the multifaceted nature of this construct.
      The purpose of this study was to examine the psychometric properties a new self
      concept measure, the Beck Self-Esteem Scale-Short Form (BSES-SF), based on a
      sample of 204 individuals with schizophrenia or schizoaffective disorder. We
      evaluated the BSES-SF's dimensionality, internal consistency reliability, and
      construct and divergent validity using confirmatory factor analysis, Cronbach's
      alpha, Pearson correlations, independent samples t-tests, and one-way analysis of
      variance. Findings indicate that the 10-item BSES-SF is a reliable and valid
      measure of self-concept that is appropriate for a broad group of individuals with
      schizophrenia spectrum disorders. Following cognitive theory, the scale
      demonstrated significant relationships with delusion severity, motivation, and
      depression, further signifying its utility for research and practice efforts that
      are designed to address psychopathology in schizophrenia.

PMID- 29573657
TI  - Reductions in self-blame cognitions predict PTSD improvements with cognitive
      processing therapy for military sexual trauma-related PTSD.
AB  - Reductions in trauma-related negative cognitions during Cognitive Processing
      Therapy (CPT) are theorized to precede posttraumatic stress disorder (PTSD)
      symptom reduction. This mechanism of change has not been validated for veterans
      with military sexual trauma-related PTSD. Using data from a previously published
      randomized clinical trial (n = 32), changes in trauma-related negative cognitions
      about self, self-blame, and the world were entered as predictors of change in
      PTSD symptoms for cross-lagged panel analyses. From baseline to 6-months
      posttreatment, only changes in self-blame predicted and temporally preceded
      changes in PTSD symptoms, highlighting a potential mechanism of change in CPT for
      military sexual trauma-related PTSD.

PMID- 29573658
TI  - Theory of mind in a first-episode psychosis population using the Hinting Task.
AB  - Deficiencies in theory of mind (ToM) are common in psychosis and may largely
      explain impaired social functioning. Currently, it is unclear whether impairments
      in ToM are explained by the more general cognitive deficits related to psychosis
      or whether ToM is impaired in psychosis independently of other cognitive
      deficits. This study examined ToM using the Hinting Task in young adults (n = 66)
      with first-episode psychosis and matched controls (n = 62). The participants were
      administered a broad neuropsychological assessment. Participants with psychosis
      performed worse than controls on the Hinting Task. However, 75% of the variance
      between the groups was explained by general cognitive deficits, especially
      impaired processing speed and episodic memory. Hinting Task performance of the
      best functioning patient group did not differ from that of the control group.
      When the psychosis group was divided according to diagnosis, the Hinting Task
      difference between individuals with schizophrenia and controls remained
      significant even when general cognitive performance was controlled for,
      suggesting specific verbal ToM deficits in schizophrenia. In contrast, those with
      other psychotic disorders did not differ from controls. Our results suggest that
      ToM deficits can be seen in early phases of psychotic disorders, schizophrenia in
      particular, and are partly independent of other cognitive functions.

PMID- 29573660
TI  - Development, validation and cultural-adaptation of the knowledge about psychosis
      questionnaire for African-Caribbean people in the UK.
AB  - The absence of assessment tools incorporating different cultural models of mental
      illness is a major barrier to recruiting ethnic minorities into clinical trials,
      reducing generalisability of findings and potentially increasing disparities in
      access to evidence-based care. This study aimed to develop and validate a new
      Knowledge about Psychosis (KAP) self-report measure and a culturally-adapted
      version for African-Caribbean people (CaKAP). Content and face validity were
      achieved through consultations with experts in psychosis and a focus group with
      service users, carers, and community members. Eighty-seven predominantly White
      British participants and 79 African-Caribbean participants completed the
      knowledge questionnaires (KAP and CaKAP) and measures of help-seeking and stigma.
      Overall, the measures showed good internal consistency and test re-test
      reliability. Construct validity was evidenced via significant positive
      associations between knowledge about psychosis and help-seeking and significant
      negative associations between knowledge and stigma. These measures could improve
      the delivery of psychosocial interventions and outcome measurement in research
      trials.

PMID- 29573659
TI  - Evaluating the genetic susceptibility to peer reported bullying behaviors.
AB  - Bullying is a significant public health concern with lasting impacts on youth.
      Although environmental risk factors for bullying have been well-characterized,
      genetic influences on bullying are not well understood. This study explored the
      role of genetics on early childhood bullying behavior. Participants were 561
      children who participated in a longitudinal randomized control trial of a
      preventive intervention beginning in first grade who were present for the first
      grade peer nominations used to measure early childhood bullying and who provided
      genetic data during the age 19-21 year follow-up in the form of blood or saliva.
      Measures included a polygenic risk score (PRS) derived from a conduct disorder
      genome wide association study. Latent profile analysis identified three profiles
      of bullying behaviors during early childhood. Results suggest that the PRS was
      significantly associated with class membership, with individuals in the moderate
      bully-victim profile having the highest levels of the PRS and those in the high
      bully-victim profile having the lowest levels. This line of research has
      important implications for understanding genetic vulnerability to bullying in
      early childhood.

PMID- 29573661
TI  - Expression patterns and role of SDF-1/CXCR4 axis in boar spermatogonial stem
      cells.
AB  - The signaling of chemokine stromal cell-derived factor (SDF)-1 and its receptor C
      X-C motif chemokine receptor 4 (CXCR4) is involved in the cellular proliferation,
      survival, and migration of various cell types. Although SDF-1/CXCR4 has been
      implicated in the maintenance of the spermatogonial population during mouse
      testis development, their expression patterns and functions in boar testis remain
      unclear. In the present study, the expression pattern of SDF-1 and CXCR4 was
      determined during pre-pubertal and post-pubertal stage boar testes and in vitro
      cultured porcine spermatogonial stem cells (pSSCs). The role of these proteins in
      colony formation in cultured pSSCs was also investigated. Interestingly, SDF-1
      expression was observed in PGP 9.5-positve spermatogonia in all developing stages
      of boar testis; however, CXCR4 expression was only detected in spermatogonia from
      5-day-old boar testis. In addition, SDF-1 and CXCR4 expression was observed in
      cultured pSSCs from 5-day-old boar testes, and inhibition of the CXCR4 receptor
      signaling pathway by AMD3100 significantly decreased the colony formation of
      pSSCs. These results suggest that SDF-1 and CXCR4 are useful markers for
      detecting stage-specific spermatogonia in boar testis. Our results reveal the
      role of the SDF-1/CXCR4 axis in pSSC in vitro culture.

PMID- 29573662
TI  - Interferon-tau regulates prostaglandin release in goat endometrial stromal cells
      via JAB1 - unfolded protein response pathway.
AB  - Prostaglandins (PGs) are major products of the uterine endometrium, and they are
      critical for recognition of pregnancy in ruminants. During the peri-implantation
      period of pregnancy, interferon tau (IFN-tau) plays an important role in the
      regulation of endometrial PGs synthesis, but the underlying mechanisms remain
      poorly understood. In this work, the results demonstrated that IFN-tau increased
      the PGE2/PGF2alpha ratio, up-regulated the expression of JAB1 and activated the
      unfolded protein response (UPR). Knockdown of JAB1 reduced the PGE2/PGF2alpha
      ratio and inhibited the expression of UPR markers in endometrial stromal cells
      (ESCs) under IFN-tau treatment. Pre-treatment with endoplasmic reticulum (ER)
      stress activator thapsigargin (Tg) activated UPR and restored the PGE2/PGF2alpha
      ratio in shJAB1 groups under IFN-tau treatment. In conclusion, our results
      indicated that IFN-tau regulated the PGE2/PGF2alpha ratio via cooperation between
      JAB1 and UPR, and the reduction of JAB1 led to the down-regulation of the
      PGE2/PGF2alpha ratio, which inhibits UPR, and thus is harmful to early pregnancy.
      Activation of UPR could restore JAB1 reduction, resulting in a reduced
      PGE2/PGF2alpha ratio. These findings extend our understanding and may provide new
      insights into the mechanism of IFN-tau regulation of PG secretion in ESCs and the
      biological functions of JAB1 and UPR.

PMID- 29573663
TI  - Capsaicin protects against testicular torsion injury through mTOR-dependent
      mechanism.
AB  - SCOPE: Testicular torsion and subsequent release of reactive oxygen species (ROS)
      can cause infertility in adults. Oxidative stress following testicular torsion
      plays an important role in the yonset and development of apoptotic cell death
      through dysregulation of the cellular signaling pathways. Anti-inflammatory and
      antioxidant properties of capsaicin, a bioactive composition present in red
      peppers, has already been exploited for treatment of the cancer and pain relief.
      In present work, we evaluated the role of the mammalian target of rapamycin
      (mTOR) in antioxidant effect of capsaicin against reperfusion injury following
      testicular torsion. METHODS: Male Wistar rats weighing 200-220 g were randomly
      assigned into four major groups: (i) a sham operated group, (ii) a testicular
      torsion (TT) group, (iii) three groups treated with different doses of capsaicin
      (TT + 100, 500 and 1000 MUg/ml Cap), and (iv) three groups of healthy rats
      treated with different doses of capsaicin (100, 500 and 1000 MUg/ml). Western
      blotting assay was used to examine the anti-apoptotic effects of capsaicin in
      testicular cells following torsion. H&E and TUNEL methods were used to evaluate
      testicular morphology and apoptosis activity. RESULTS: Compared to control group,
      phosphorylation of mTOR was significantly increased in the TT groups. Capsaicin
      administration remarkably decreased the phosphorylation of mTOR at the highest
      dose (P < 0.05). Capsaicin decreased apoptosis and preserved tubular morphology
      in testes. CONCLUSION: Our results showed that antioxidant properties of
      capsaicin minimizes cell death and reperfusion injury following testicular
      torsion.

PMID- 29573664
TI  - MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through
      envelope protein translocation or degradation.
AB  - MARCH2 is one of the MARCH family E3 ligases, which contains eleven members that
      play pivotal roles in controlling the turn-over of membrane proteins, such as MHC
      class I, MHC class II, and cell surface receptors. In this study, we found the
      expression of MARCH2 to be upregulated upon HIV-1 infection. MARCH2 inhibits the
      production and infection of HIV-1 through ligase activity-dependent envelope
      protein degradation and/or intracellular retention, a mechanism shared by MARCH8
      that also leads to the inhibition of HIV-1 infection. Nevertheless, unlike MARCH8
      and other MARCH proteins whose transcription levels are unrelated to viral
      infection, the expression level of MARCH2 is markedly upregulated upon HIV-1
      infection, conferring MARCH2 a unique role in monitoring and regulating the HIV-1
      infection-associated process.

PMID- 29573665
TI  - Outcomes of single versus double hormone receptor-positive breast cancer. A
      GEICAM/9906 sub-study.
AB  - BACKGROUND: Retrospective data suggest better outcomes for patients with double
      hormonal receptor (oestrogen [ER] and progesterone receptor [PgR])-positive
      (dHR+) early breast cancer, compared with single hormonal receptor-positive,
      sHR+, (ER+/PgR- or ER-/PgR+) disease. Here, we evaluate the classification
      according to intrinsic subtypes and clinical outcomes of sHR+ versus dHR+ in HER2
      negative breast cancer patients enrolled in GEICAM/9906 study (NCT00129922).
      METHODS: Archival tumours were retrieved retrospectively for the analysis of ER,
      PgR and HER2 status and classified into intrinsic subtypes using the PAM50 gene
      expression assay. Disease-free survival (DFS) and overall survival (OS) were
      explored using a Cox proportional hazard analysis. RESULTS: Data on intrinsic
      subtypes were available in 571 (50%) patients with ER+ and/or PR+, and HER2
      negative primary tumours. The incidence of luminal A and luminal B subtypes were
      52%/36% in dHR+ tumours (ER+/PgR+), and 15%/58% in ER+/PgR-tumours. ER-/PgR+
      tumours were mainly luminal A (52%). Compared with ER+/PgR+ patients, DFS was
      similar in ER-/PgR+ (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.57
      2.34, p = 0.70) but worse in ER+/PgR- patients (HR 1.60, 95% CI 1.12-2.28, p <
      0.01). Similar results were observed for OS (HR 1.50, p = 0.30 and HR 1.86, p <
      0.01, respectively). CONCLUSIONS: The ER+/PgR- group is characterised by higher
      proliferation and worse outcomes. In spite of the ER-/PgR+ subgroup resembles
      ER+/PgR+ disease in terms of molecular subtypes and outcomes, the small number of
      patients in this subgroup prevents from drawing any conclusions. TRIAL
      REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005).
      CLINICALTRIALS. GOV IDENTIFIER: NCT00129922 (retrospectively registered
      10/08/2005).

PMID- 29573666
TI  - Foot posture is associated with plantar pressure during gait: A comparison of
      normal, planus and cavus feet.
AB  - BACKGROUND: Variations in foot posture, such as pes planus (low medial
      longitudinal arch) or pes cavus (high medial longitudinal arch) are associated
      with some lower limb injuries. However, the mechanism that links foot posture to
      injury is not clear. Research question The aim of this study was to compare
      plantar pressure between healthy individuals with normal, planus or cavus feet.
      METHODS: Ninety-two healthy volunteers (aged 18 to 45) were classified as either
      normal (n = 35), pes planus (n = 31) or pes cavus (n = 26) based on the Foot
      Posture Index, Arch Index and normalised navicular height truncated. Barefoot
      walking trials were conducted using an emed(r)-x400 plantar pressure system
      (Novel GmbH, Munich, Germany). An 11 region mask was used that included the
      medial heel, lateral heel, midfoot, 1st, 2nd, 3rd, 4th and 5th
      metatarsophalangeal joints, hallux, 2nd toe, and the 3rd, 4th and 5th toes. Peak
      pressure, pressure-time integral, maximum force, force-time integral and contact
      area were calculated for each region. One way analyses of variance and effect
      sizes were used to compare the three foot posture groups. RESULTS: Overall, the
      largest differences were between the planus and cavus foot groups in forefoot
      pressure and force. In particular, peak pressures at the 4th and 5th MTPJs in the
      planus foot group were lower compared to the normal and cavus foot groups, and
      displayed the largest effect sizes. Significance This study confirms that foot
      posture does influence plantar pressures, and that each foot posture
      classification displays unique plantar pressure characteristics.

PMID- 29573667
TI  - Glycaemic variability-based classification of impaired glucose tolerance vs. type
      2 diabetes using continuous glucose monitoring data.
AB  - Many glycaemic variability (GV) indices extracted from continuous glucose
      monitoring systems data have been proposed for the characterisation of various
      aspects of glucose concentration profile dynamics in both healthy and non-healthy
      individuals. However, the inter-index correlations have made it difficult to
      reach a consensus regarding the best applications or a subset of indices for
      clinical scenarios, such as distinguishing subjects according to diabetes
      progression stage. Recently, a logistic regression-based method was used to
      address the basic problem of differentiating between healthy subjects and those
      affected by impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in a pool
      of 25 GV-based indices. Whereas healthy subjects were classified accurately, the
      distinction between patients with IGT and T2D remained critical. In the present
      work, by using a dataset of CGM time-series collected in 62 subjects, we
      developed a polynomial-kernel support vector machine-based approach and
      demonstrated the ability to distinguish between subjects affected by IGT and T2D
      based on a pool of 37 GV indices complemented by four basic parameters-age, sex,
      BMI, and waist circumference-with an accuracy of 87.1%.

PMID- 29573668
TI  - Accurate label-free 3-part leukocyte recognition with single cell lens-free
      imaging flow cytometry.
AB  - Three-part white blood cell differentials which are key to routine blood workups
      are typically performed in centralized laboratories on conventional hematology
      analyzers operated by highly trained staff. With the trend of developing
      miniaturized blood analysis tool for point-of-need in order to accelerate
      turnaround times and move routine blood testing away from centralized facilities
      on the rise, our group has developed a highly miniaturized holographic imaging
      system for generating lens-free images of white blood cells in suspension.
      Analysis and classification of its output data, constitutes the final crucial
      step ensuring appropriate accuracy of the system. In this work, we implement
      reference holographic images of single white blood cells in suspension, in order
      to establish an accurate ground truth to increase classification accuracy. We
      also automate the entire workflow for analyzing the output and demonstrate clear
      improvement in the accuracy of the 3-part classification. High-dimensional
      optical and morphological features are extracted from reconstructed digital
      holograms of single cells using the ground-truth images and advanced machine
      learning algorithms are investigated and implemented to obtain 99% classification
      accuracy. Representative features of the three white blood cell subtypes are
      selected and give comparable results, with a focus on rapid cell recognition and
      decreased computational cost.

PMID- 29573669
TI  - The effect of a tactile-to-visual shift on young children's tendency to map novel
      labels onto novel objects.
AB  - When taught a label for an object and then asked whether an exemplar of that
      object or a novel object is the referent of a novel label, children favor the
      novel object. Preschool-aged children tend not to show this so-called
      disambiguation effect, however, when the test objects are presented in a
      different sense modality than the original object. The current experiments used a
      touch-to-vision paradigm to test two explanations for this unexpected pattern.
      Experiment 1 asked whether children might fail to retrieve the original label and
      found that additional label training benefitted 3-year-olds but not 4-year-olds.
      Experiments 2 and 3 asked whether children's reaction to discovering the cross
      modal match might interfere with how they process the request for the novel label
      and found that being allowed to share their discovery of the match benefitted 4
      year-olds but not 3-year-olds. These findings support the proposal that the chief
      obstacle to cross-modal disambiguation changes during early childhood from
      difficulty in retrieving the known label to disruption caused by the discovery of
      the cross-modal match.

PMID- 29573670
TI  - Children's visual attention to emotional expressions varies with stimulus
      movement.
AB  - The majority of studies of emotion perception have relied on static isolated
      facial expressions. These expressions differ markedly from real-world expressions
      that include movement and multiple cues (e.g., bodies), leaving our understanding
      of how expression perception develops incomplete. We examined the looking
      patterns of younger children (4- and 5-year-olds), older children (8- and 9-year
      olds), and adults while watching dynamic video clips or static images of four
      different emotional expressions: happiness, sadness, anger, and fear. Expressions
      were presented in three conditions: face only, body only, and whole person (face
      and body). Children's and adults' looking patterns were affected by whether
      stimuli were static or dynamic and by which cues were available. Children looked
      to the head less for static stimuli than for dynamic stimuli, but this difference
      did not emerge for adults. Children and adults attended to different expression
      cues when presented with static images. These results demonstrate the need for
      increased use of dynamic stimuli in developmental studies of expression.

PMID- 29573671
TI  - Biofloc improves water, effluent quality and growth parameters of Penaeus
      vannamei in an intensive culture system.
AB  - Biofloc technology was evaluated with a view to analyse utilization of
      nitrogenous waste from the effluent and to improve water quality and growth
      parameters of Penaeus vannamei in intensive culture system. The experiment was
      carried out in two different treatment outdoor earthen ponds of 0.12 ha, one
      supplemented with carbon source (molasses, wheat and sugar) for biofloc formation
      and other was feed based control pond with a stocking density of 60 animals m-2
      in duplicate for 120 days. Water, sediment and P. vannamei were sampled at
      regular intervals from the both set of ponds for evaluating physico-chemical
      parameters, nitrogen content and growth parameters, respectively. A significant
      reduction in the concentration of total ammonia nitrogen (TAN) and nitrite (NO2
      N) were found in the biofloc pond than that of control pond. A significant low
      level of nitrogen was recorded in the effluents of biofloc pond in comparison to
      the control. In biofloc system, a significantly elevated heterotrophic bacterial
      count along with reduction in total Vibrio count was noticed. A significant
      improvement in the feed conversion efficiency (FCR) and growth parameters of P.
      vannamei was noticed in the biofloc pond. Growth of P. vannamei in the biofloc
      pond showed positive allometric pattern with an increased survival. The microbial
      biomass grown in biofloc consumes toxic inorganic nitrogen and converts it into
      useful protein, making it available for the cultured shrimp. This improved FCR
      and reduced the discharge of nitrogenous waste into adjacent environment, making
      intensive shrimp farming an eco-friendly enterprise.

PMID- 29573672
TI  - Degradation of 4-chlorophenol and microbial diversity in soil inoculated with
      single Pseudomonas sp. CF600 and Stenotrophomonas maltophilia KB2.
AB  - Soil contamination with chlorophenols is a serious problem all over the world due
      to their common use in different branches of industry and agriculture. The
      objective of this study was to determine whether bioaugmenting soil with single
      Pseudomonas sp. CF600 and Stenotrophomonas maltophilia KB2 and additional carbon
      sources such as phenol (P) and sodium benzoate (SB) could enhance the degradation
      of 4-chlorophenol (4-CP). During the degradation experiment, the number of
      bacteria as well as the structural and functional diversity of the soil microbial
      communities were determined. It was found that the most effective degradation of
      4-CP in the soil was observed after it was inoculated with CF600 and the addition
      of SB. The biodegradation of five doses of 4-CP in this soil proceeded within 100
      days. At the same time, the rate of the disappearance of 4-CP in the soil that
      had been bioaugmented with CF600 and contaminated with 4-CP and P was 5-6.5 times
      lower compared to its rate of disappearance in the soil that had been
      contaminated with 4-CP. The biodegradation of 4-CP in all of the treated and
      untreated soils was accompanied by a systematic decrease in the number of
      heterotrophic bacteria (THB) ranging between 13 and 40%. It was also proven that
      the tested aromatic compounds affected the soil microbial community structure
      through an increase in the marker fatty acids for Gram-negative bacteria (BG-)
      and fungi (F). The essential changes in the patterns of the fatty acid methyl
      esters (FAMEs) for the polluted soil included an increase in the fatty acid
      saturation and hydroxy fatty acid abundance. The obtained results also indicated
      that the introduction of CF600 into the soil contaminated with 4-CP and SB or P
      caused an increase in the functional diversity of the soil microorganisms. In
      contrast, in the soil that had been inoculated with KB2 and in the non-inoculated
      soil, the addition of 4-CP and P decreased the microbial activity. In conclusion,
      the inoculation of both strains into contaminated soil with aromatic compounds
      caused irreversible changes in the functional and structural diversity of the
      soil microbial communities.

PMID- 29573673
TI  - The effect of water velocity on nitrate removal in vegetated waterways.
AB  - The extended networks of canals and ditches in agricultural landscapes provide
      high buffer capacity towards nitrogen (N) excess. Their N mitigation potential
      depends on several biotic and abiotic factors, among which water velocity is
      poorly explored and generally omitted from the parameterization of this
      remarkable ecosystem service. The present work reports new insights on the role
      of flow velocity in regulating N removal via denitrification in sediments
      colonized by Phragmites australis. Denitrification was investigated in outdoor
      mesocosms in the presence and absence of P. australis and over a small range of
      flow velocity (0-6 cm s-1) typical of low-gradient water bodies. Simultaneous
      measurements of NO3- consumption and N2 production based on analyses of N2:Ar by
      Membrane Inlet Mass Spectrometry were undertaken. Vegetated sediments were found
      more efficient in converting NO3- to N2 via microbial-mediated denitrification
      (27-233 mmol N m-2 d-1) than bare sediments (18-33 mmol N m-2 d-1). Vegetation
      provides multiple interfaces, i.e. in the rhizosphere and on epiphytic biofilms,
      that support the development and activity of bacterial communities responsible
      for NO3- dissipation. NO3- removal and denitrification rates exhibited one order
      of magnitude raise when water velocity passed from 0 to 6 cm s-1 in vegetated
      sediments. Indeed, in slow-flow vegetated waterways denitrification may be
      physically limited and the increase of water velocity enhances the rate of NO3-
      supply through the diffusive boundary layer, thereby promoting its consumption
      and loss from the system. Water velocity should be taken into account as a key
      factor for management and restoration actions aimed at maximizing the NO3- buffer
      capacity of low-flow drainage networks.

PMID- 29573674
TI  - Competing actors in the climate change arena in Mexico: A network analysis.
AB  - This paper analyzes the actors in the climate change arena and their influence in
      directing Mexico toward policies that decrease greenhouse gas emissions, such as
      the carbon tax and climate change law. The network analysis of the agreement of
      these laws and public policies in Mexico is a lesson for any country that is in
      the process of designing and adopting environmental laws. The research is
      performed using a network analysis that is derived from interviews with various
      main actors and a discourse analysis of the media. Results show that actors do
      not coordinate their efforts-they meet frequently but in different inter
      ministerial commissions-and do not enforce the same policies. The actors in the
      industry have formed strong coalitions against the carbon tax and the General Law
      on Climate Change, whereas international institutions have formed coalitions that
      support these policies and laws.

PMID- 29573675
TI  - Short-term effects of nanoscale Zero-Valent Iron (nZVI) and hydraulic shock
      during high-rate anammox wastewater treatment.
AB  - The stability and resilience of an anaerobic ammonium oxidation (anammox) system
      under transient nanoscale Zero-Valent Iron (nZVI) (50, 75 and 100 mg L-1),
      hydraulic shock (2-fold increase in flow rate) and their combination were studied
      in an up-flow anaerobic sludge blanket reactor. The response to the shock loads
      can be divided into three phases i.e. shock, inertial and recovery periods. The
      effects of the shock loads were directly proportional to the shock intensity. The
      effluent quality was gradually deteriorated after exposure to high nZVI level
      (100 mg L-1) for 2 h. The higher effluent sensitivity index and response caused
      by unit intensity of shock was observed under hydraulic and combined shocks.
      Notably, the specific anammox activity and the content of heme c were
      considerably reduced during the shock phase and the maximum loss rates were about
      30.5% and 24.8%, respectively. Nevertheless, the extracellular polymeric
      substance amount in the shock phase was enhanced in varying degrees and variation
      tendency was disparate at all the tested shock loads. These results suggested
      that robustness of the anammox system was dependent on the magnitude shocks
      applied and the reactor resistance can be improved by reducing hydraulic
      retention time with the increase of nZVI concentration under these circumstances.

PMID- 29573676
TI  - Life cycle environmental impacts of advanced wastewater treatment techniques for
      removal of pharmaceuticals and personal care products (PPCPs).
AB  - Pharmaceutical and personal care products (PPCPs) are of increasing interest
      because of their ecotoxicological properties and environmental impacts.
      Wastewater treatment plants (WWTPs) are the main pathway for their release into
      freshwaters due to the inefficiency of conventional WWTPs in removing many of
      these contaminants from effluents. Therefore, different advanced effluent
      treatment techniques have been proposed for their treatment. However, it is not
      known at present how effective these treatment methods are and whether on a life
      cycle basis they cause other environmental impacts which may outweigh the
      benefits of the treatment. In an effort to provide an insight into this question,
      this paper considers life cycle environmental impacts of the following advanced
      treatment techniques aimed at reducing freshwater ecotoxicity potential of PPCPs:
      granular activated carbon (GAC), nanofiltration (NF), solar photo-Fenton (SPF)
      and ozonation. The results suggest that on average NF has the lowest impacts for
      13 out of 18 categories considered. GAC is the best alternative for five impacts,
      including metals and water depletion, but it has the highest marine
      eutrophication. SPF and ozonation are the least sustainable for eight impacts,
      including ecotoxicity and climate change. GAC and NF are also more efficient in
      treating heavy metals while avoiding generation of harmful by-products during the
      treatment, thus being more suitable for potable reuse of wastewater. However,
      releasing the effluent without advanced treatment to agricultural land achieves a
      much higher reduction of freshwater ecotoxicity than treating it by any of the
      advanced treatments and releasing to the environment. Therefore, the use of
      advanced effluent treatment for agricultural purposes is not recommended.

PMID- 29573677
TI  - Vertical air temperature gradients under the shade of two contrasting urban tree
      species during different types of summer days.
AB  - Moderation of thermal energy balance through the canopies of urban trees is well
      known. However, a more functional and quantitative view of the heterogeneous
      urban environment and their influence on the below-canopy vertical air
      temperature gradients is largely missing. Throughout the summer 2016 we
      continuously measured air temperature at three different heights (at 1.5, 3 and
      4.5m from the ground) under the canopies of two common but contrasting street
      tree species in respect of eco-physiology and morphology in Munich, Germany:
      Robinia pseudoacacia L. (ring porous) and Tilia cordata Mill. (diffuse porous).
      Along with air and surface temperature we also measured meteorological and
      edaphic variables and categorized summer time as cool, mild, summer and hot days.
      Global radiation, vapour pressure deficit and soil temperature increased as the
      days got warmer but precipitation, soil moisture and wind speed showed the
      reversed pattern. Overall, T. cordata trees with higher leaf area index and sap
      wood area provided three times more transpiration than R. pseudoacacia. On an
      average air temperature gradient of outside to inside canopy dropped from 1.8
      degrees C to 1.3 degrees C for T. cordata but from 1.5 degrees C to only 0.5
      degrees C for R. pseudoacacia as the days got warmer. Vertical decline of air
      cooling effect was around 1 degrees C from canopy to the near-ground (1.5m).
      Lower soil moisture but higher soil temperature suggested that cool air from the
      canopy mixed with a higher amount of sensible heat flux under the canopies of T.
      cordata compared to the R. pseudoacacia as the days got warmer. The study
      indicated a threshold for extreme hot days when grass surface
      evapotranspirational cooling will not be as effective and act like built surfaces
      rather deep shading from tree canopies will be important.

PMID- 29573678
TI  - Bioreceptivity index for granitic rocks used as construction material.
AB  - Bioreceptivity is a fundamental concept in the ornamental stone industry and in
      the fields of cultural heritage and civil engineering to understand the
      susceptibility of stone constructions to biological colonisation and subsequent
      biodeterioration. However, a bioreceptivity index (BI) has not yet been
      established for any construction material. The aim of the present study is
      developing a simple, robust and well-founded BI for granitic rocks. For this
      purpose, a standardised laboratory protocol was used to grow phototrophic
      biofilms on several varieties of granite. The colonisation was then assessed by
      chlorophyll fluorescence and colour measurements. Based on the results thus
      obtained, a BI including two components (BIgrowth and BIcolour) is proposed.
      BIgrowth quantifies the extent of the biological growth and BIcolour quantifies
      the colour change undergone by the stone due to the colonisation, which can be
      considered the bioreceptivity perceptible to the human eye. The values of BI,
      BIgrowth and BIcolour were fitted to a scale of 0-10, thus enabling qualitative
      classification of the lithotypes according to their primary bioreceptivity.
      Eleven varieties of granite commonly used as construction material and with a
      honed surface finish (one variety with three additional surface finishes:
      polished, sawn and sanded) were thus assigned the corresponding BI, which
      represents a new quality factor for the stone industry. The index can therefore
      be used by end-users as a decision-making tool in the selection of appropriate
      lithotypes for building and/or ornamental purposes.

PMID- 29573679
TI  - A framework to overcome barriers to green innovation in SMEs using BWM and Fuzzy
      TOPSIS.
AB  - Recent years have witnessed a significant rise in exploring the barriers which
      obstruct adoption of green practices by SMEs. There is a constant need to
      innovate in terms of products, processes, and management so that we can overcome
      these barriers to green practices adoption and implementation. This study employs
      a three-phase methodology to identify barriers and solutions to overcome these
      barriers to green innovation in SMEs. Through extensive literature review and the
      opinion of selective manager's, seven main category barriers, thirty-six sub
      category barriers, and twenty solutions to overcome these barriers were
      identified. BWM is used to rank these barriers and Fuzzy TOPSIS is used to rank
      solutions to overcome these barriers. Four Indian SMEs are taken to exemplify the
      proposed three paged model. To check the robustness of the model, a sensitivity
      analysis was also performed. The results of the analysis can act as a stepping
      stone for SME managers to eliminate and overcome barriers to green innovation in
      their firm and compete healthily in the market. The paper sets a framework for
      future studies in this area of research-work.

PMID- 29573680
TI  - Quantifying direct carbon dioxide emissions from wastewater treatment units by
      nondispersive infrared sensor (NDIR) - A pilot study.
AB  - Treatment of nutrient-rich wastewater potentially results in direct release of
      greenhouse gases (GHGs) such as CO2, N2O or CH4 - and thus affects Waste Water
      Treatment Plant's carbon footprint. Accurate CO2 quantification is challenging
      due to various chemical, physical and operational conditions. A floating chamber
      equipped with a nondispersive infrared, single beam, dual wavelength sensor has
      been evaluated for a pilot approach to quantify fugitive CO2 emissions above
      different wastewater treatment units. Total average CO2 flux was 1182gCO2.m-2.d-1
      with minimum and maximum fluxes of 829gCO2.m-2.d-1 and 1493gCO2.m-2.d-1,
      respectively. Total observed CO2 emissions were in 7 to 17kgCO2.PE-1.a-1 (average
      12kgCO2.PE-1.a-1). The nitrification tank accounted for about 94.3% of the
      emissions, followed by secondary clarification (ca. 4.3%) and denitrification
      (ca. 1.4%), based on those average annual CO2 emissions per population equivalent
      (PE).

PMID- 29573681
TI  - Understanding intricacies of clogging and its alleviation by introducing
      earthworms in soil biofilters.
AB  - With the scarcity of fresh water and rise in pollution load in the aquatic
      ecosystem over the globe, the domestic and industrial effluents need to be reused
      after suitable treatment. In an attempt to do so, soil biofilters have been
      identified as a treatment alternative that is suitable for application in
      developing countries. However, rapid development of clogging in the soil
      biofilters limits its applicability as an effective technology. This paper aims
      to understand the occurrence of clogging due to biofilms formation in and over
      the bedding of soil media. To address this, the organic loading rates (OLRs) were
      varied in the range of 2.25-11.25kgCOD/m3.day to create different degree of
      clogging. Earthworms were inoculated into the soil bedding at the earthworm
      densities (EWDs) of 0, 5000 and 10,000earthworms/m3 to study the effect of
      earthworms introduction on clogging. The degree of clogging was measured using
      clogging coefficient (CC), hydraulic conductivity and head loss. The study
      highlights the impact of earthworms on the removal performance and clogging of
      soil biofilter. For all earthworm densities, head loss and clogging coefficient
      increased and hydraulic conductivity decreased linearly with organic loading
      rate. Introduction of earthworms versus no earthworms resulted in lower head loss
      and clogging coefficient and higher hydraulic conductivity for all organic
      loading rates, while increasing EWD from 5000 to 10,000 had only marginal effects
      on all parameters. The study reveals that high organic loading rate activates
      higher number of microbial sites, in turn causing higher degree of clogging.
      However, the introduction of earthworms reduces the clogging rate significantly
      along with enhanced treatment performance. The outcome of this study indicates
      that incorporation of earthworms into the soil biofilter can reduce the degree of
      bio-clogging and might provide a highly sustainable, low cost and efficient
      treatment system for the developing countries.

PMID- 29573682
TI  - Enrichment of free-living amoebae in biofilms developed at upper water levels in
      drinking water storage towers: An inter- and intra-seasonal study.
AB  - Free-living amoebae (FLA) are ubiquitous organisms present in various natural and
      artificial environments, such as drinking water storage towers (DWST). Some FLA,
      such as Acanthamoeba sp., Naegleria fowleri, and Balamuthia mandrillaris, can
      cause severe infections at ocular or cerebral level in addition to being
      potential reservoirs of other pathogens. In this work, the abundance and
      diversity of FLA was evaluated in two sampling campaigns: one performed over five
      seasons in three DWST at three different levels (surface, middle and bottom) in
      water and biofilm using microscopy and PCR, and one based on the kinetics
      analysis in phase contrast and confocal microscopy of biofilm samples collected
      every two weeks during a 3-month period at the surface and at the bottom of a
      DWST. In the seasonal study, the FLA were detected in each DWST water in
      densities of ~20 to 25amoebaeL-1. A seasonal variation of amoeba distribution was
      observed in water samples, with maximal densities in summer at ~30amoebaeL-1 and
      minimal densities in winter at ~16amoebaeL-1. The FLA belonging to the genus
      Acanthamoeba were detected in two spring sampling campaigns, suggesting a
      possible seasonal appearance of this potentially pathogenic amoeba.
      Interestingly, a 1 log increase of amoebae density was observed in biofilm
      samples collected at the surface of all DWST compared to the middle and the
      bottom where FLA were at 0.1-0.2amoebae/cm2. In the kinetics study, an increase
      of amoebae density, total cell density, and biofilm thickness was observed as a
      function of time at the surface of the DWST, but not at the bottom. To our
      knowledge, this study describes for the first time a marked higher FLA density in
      biofilms collected at upper water levels in DWST, constituting a potential source
      of pathogenic micro-organisms.

PMID- 29573683
TI  - Inhibition of biofilm growth on polymer-MWCNTs composites and metal surfaces.
AB  - There is an increased interest in incorporating multi-wall carbon nanotubes
      (MWCNTs) into polymer matrices to control the adhesion of bacteria to surfaces
      and the subsequent formation of biofilm growth on the surface of water pipes,
      food packages, and medical devices. Microbial interactions with carbon nanotube
      polymer composites in the environment are not well understood. The growth of
      Pseudomonas fluorescens (gram-negative) and Mycobacterium smegmatis (gram
      positive) biofilms on copper, polyethylene (PE), polyvinyl chloride, and
      stainless steel was compared with growth on MWCNT-PE composites in order to gain
      insight into the effect of the surface properties of nanomaterials on the
      attachment and proliferation of microorganism which could result in the
      engineering of better, non-fouling materials. A statistical analysis of the
      biofilm growth showed a significant impact of materials for both P. fluorescens
      (p < 0.0001) and M. smegmatis (p = 0.00426). Biofilm growth after 56 days on PE
      compared to biofilm growth on copper surfaces decreased by 46.4% and 34.9% for P.
      fluorescens and M. smegmatis, respectively. Biofilm growth on PE-multiwall-carbon
      nanotubes (MWCNTs)-composites surface compared to PE decreased by 89.3% and 29%
      for P. fluorescens and M. smegmatis, respectively. Bacterial species (p < 0.0006)
      and surface roughness (p < 0.0001) were important factors in determining the
      attachment and initial biofilm growth rate. The interactions between cells and
      material surface could be attributed to the complicated and collective effect of
      electrostatic forces, hydrophobic interactions, and hydrogen/covalent bonding.
      Further study is needed to determine whether or not there is a difference between
      the cell attachment in the exponential growth phase and the stationary, or decay,
      phase cells.

PMID- 29573684
TI  - Assessing the extent and relative risk of aquatic stressors on stream
      macroinvertebrate assemblages in the neotropical savanna.

PMID- 29573685
TI  - Upgrading the Chinese biggest petrochemical wastewater treatment plant:
      Technologies research and full scale application.
AB  - The components of petrochemical wastewater (PCWW) are very complex and it is one
      of the most important sources of organic micropollutants (OMPs) in water bodies.
      To improve the effluent qualities of PCWW, the Chinese government has promulgated
      a new Emission Standard of Pollutants for Petroleum Chemistry Industry. More than
      60 types of OMPs, most of which are toxic organics, are added and strictly
      limited in the standard. Based on the bench- and pilot-scale experiments, a
      pretreatment (microaerobic hydrolysis and acidification, MOHA), biological
      (anoxic/oxic process, A/O) and advanced treatment (micro-flocculation dynasand
      filtration and catalytic ozonation, MFDF-CO) integrated process is proposed. The
      full-scale application in the Chinese biggest petrochemical wastewater treatment
      plant has demonstrated that the performance of the integrated process is stable
      and it can significantly improve the effluent qualities. The effluent COD
      decreased from 84.7 to 47.0mg/L and most of the OMPs were removed. The EC50 of
      the effluent for luminescent bacteria assay, algal growth inhibition, Daphnia
      magna inhibition test and zebrafish eggs test are all higher than 100% and the
      induction rate (IR) for genotoxicity is only 0.76. The energy demand, however,
      with the electricity consumption increase by 44.1%, is very high for OMPs
      removal, leading to high indirect carbon emission.

PMID- 29573686
TI  - Experimental and theoretical analyses on the impacts of ionic surfactants on
      sludge properties.
AB  - A large amount of excess waste activated sludge is produced in municipal
      wastewater treatment plants and should be further disposed to avoid environmental
      pollution. Ionic surfactants are being widely used for sludge conditioning, but
      how and to what extent ionic surfactants change the sludge properties remain
      unclear. In this work, the impacts of two typical ionic surfactants on the
      flocculability and stability of sludge were investigated by using experimental
      and theoretical analyses. The treatment of anionic sodium dodecyl sulfate (SDS)
      resulted in more detachment of extracellular materials and fluorophores from
      sludge compared to the treatment of cationic trimethyl ammonium bromide (DTAB).
      Fourier transform infrared spectra analysis indicates the promoted release of
      proteins and polysaccharides induced by the surfactants. Deteriorated
      flocculability of sludge was observed for the SDS-treated sludge, while treatment
      of DTAB slightly affected the overall sludge flocculability. The sludge floc
      structure became less stable after treatments of both surfactants, as confirmed
      by the elevated dispersed mass concentration of small particles in shearing
      tests. The relationship between the content of extracellular polymeric
      substances, surfactant dose and sludge properties were evaluated and the roles of
      released extracellular polymeric substances and surfactant dose in affecting
      sludge flocculability were examined. Extended DLVO approach was adopted to
      explore the stability of sludge. By using such an integrated approach, the
      impacts of ionic surfactants on sludge flocculability and stability were
      revealed, which is useful in understanding the mechanisms of sludge conditioning
      by surfactant treatment.

PMID- 29573687
TI  - Remediation techniques for heavy metal-contaminated soils: Principles and
      applicability.
AB  - Globally there are over 20millionha of land contaminated by the heavy
      metal(loid)s As, Cd, Cr, Hg, Pb, Co, Cu, Ni, Zn, and Se, with the present soil
      concentrations higher than the geo-baseline or regulatory levels. In-situ and ex
      situ remediation techniques have been developed to rectify the heavy metal
      contaminated sites, including surface capping, encapsulation, landfilling, soil
      flushing, soil washing, electrokinetic extraction, stabilization, solidification,
      vitrification, phytoremediation, and bioremediation. These remediation techniques
      employ containment, extraction/removal, and immobilization mechanisms to reduce
      the contamination effects through physical, chemical, biological, electrical, and
      thermal remedy processes. These techniques demonstrate specific advantages,
      disadvantages, and applicability. In general, in-situ soil remediation is more
      cost-effective than ex-situ treatment, and contaminant removal/extraction is more
      favorable than immobilization and containment. Among the available soil
      remediation techniques, electrokinetic extraction, chemical stabilization, and
      phytoremediation are at the development stage, while the others have been
      practiced at full, field scales. Comprehensive assessment indicates that chemical
      stabilization serves as a temporary soil remediation technique, phytoremediation
      needs improvement in efficiency, surface capping and landfilling are applicable
      to small, serious-contamination sites, while solidification and vitrification are
      the last remediation option. The cost and duration of soil remediation are
      technique-dependent and site-specific, up to $500ton-1 soil (or $1500m-3 soil or
      $100m-2 land) and 15years. Treatability studies are crucial to selecting feasible
      techniques for a soil remediation project, with considerations of the type and
      degree of contamination, remediation goals, site characteristics, cost
      effectiveness, implementation time, and public acceptability.

PMID- 29573688
TI  - Coupling hydrological modeling and support vector regression to model
      hydropeaking in alpine catchments.
AB  - Water management in the alpine region has an important impact on streamflow. In
      particular, hydropower production is known to cause hydropeaking i.e., sudden
      fluctuations in river stage caused by the release or storage of water in
      artificial reservoirs. Modeling hydropeaking with hydrological models, such as
      the Soil Water Assessment Tool (SWAT), requires knowledge of reservoir management
      rules. These data are often not available since they are sensitive information
      belonging to hydropower production companies. In this short communication, we
      propose to couple the results of a calibrated hydrological model with a machine
      learning method to reproduce hydropeaking without requiring the knowledge of the
      actual reservoir management operation. We trained a support vector machine (SVM)
      with SWAT model outputs, the day of the week and the energy price. We tested the
      model for the Upper Adige river basin in North-East Italy. A wavelet analysis
      showed that energy price has a significant influence on river discharge, and a
      wavelet coherence analysis demonstrated the improved performance of the SVM model
      in comparison to the SWAT model alone. The SVM model was also able to capture the
      fluctuations in streamflow caused by hydropeaking when both energy price and
      river discharge displayed a complex temporal dynamic.

PMID- 29573689
TI  - Source apportionment and carcinogenic risk assessment of passive air sampler
      derived PAHs and PCBs in a heavily industrialized region.
AB  - Cancer has become the primary reason of deaths in Dilovasi probably due to its
      location with unique topography under the influence of heavy industrialization
      and traffic. In this study, possible sources and carcinogenic health risks of
      PAHs and PCBs were investigated in Dilovasi region by Positive Matrix
      Factorization (PMF) and the USEPA approach, respectively. PAHs and PCBs were
      measured monthly for a whole year at 23 sampling sites using PUF disk passive
      samplers. Average ambient air concentrations were found as 285+/-431ng/m3 and
      4152+/-6072pg/m3, for Sigma15PAH and Sigma41PCB, respectively. PAH concentrations
      increased with decreasing temperature especially at urban sites, indicating the
      impact of residential heating in addition to industrial activities and traffic.
      On the other hand, PCB concentrations mostly increased with temperature probably
      due to enhanced volatilization from their sources. Possible sources of PAHs were
      found as emissions of diesel and gasoline vehicles, biomass and coal combustion,
      iron and steel industry, and unburned petroleum/petroleum products, whereas iron
      steel production, coal and biomass burning, technical PCB mixtures, and
      industrial emissions were identified for PCBs. The mean carcinogenic risk
      associated with inhalation exposure to PAHs and PCBs were estimated to be >10-6
      and >10-5, respectively, at all sampling points, while the 95th percentile was
      >10-5 at 15 of 23 and >10-4 at 8 of 23 sampling locations, respectively.
      Probabilistic assessment showed, especially for PCBs, that a majority of Dilovasi
      population face significant health risks. The higher risks due to PCBs further
      indicated that PCBs and possibly other pollutants originating from the same
      sources such as PBDEs and PCNs may be an important issue for the region.

PMID- 29573690
TI  - The Lake Urmia environmental disaster in Iran: A look at aerosol pollution.
AB  - Lake Urmia (LU) once was the second largest hypersaline lake in the world,
      covering up to 6000km2, but has undergone catastrophic desiccation in recent
      years resulting in loss of 90% of its area and extensive coverage by playas and
      marshlands that represent a source of salt and dust. This study examines daily
      Aerosol Optical Depth (AOD) data from the Moderate Resolution Imaging
      Spectroradiometer (MODIS) between 2001 and 2015 over northwestern Iran, which
      encompasses LU. Intriguingly, salt emissions from the LU surface associated with
      ongoing desiccation do not drive the study region's AOD profile, whereas
      pollution transported from other regions and emissions around LU are more
      important. Signatures of increasing local crustal emissions are most evident
      outside of the peak dust season (January, February, and October) and on the
      periphery of LU. AOD has generally increased in the latter half of the study
      period with the onset of the AOD ramp-up starting a month earlier in the spring
      season when comparing 2009-2015 versus earlier years. Results indicate that
      suppression of emissions on the LU border is critical as the combined area of
      salt and salty soil bodies around LU have increased by two orders of magnitude in
      the past two decades, and disturbing these areas via activities such as grazing
      and salt harvesting on the lake surface can have more detrimental impacts on
      regional pollution as compared to benefits. These results have important
      implications for public health, climate, the hydrological cycle, and pollution
      control efforts.

PMID- 29573691
TI  - Water quality in the tropical Andes hotspot: The Yacuambi river (southeastern
      Ecuador).
AB  - Yacuambi river waters (southeast Ecuador, Amazonian region) were assessed to
      evaluate the potential risk to populations, who use it for drinking and
      irrigation, and ecosystems, which are part of Tropical Andes hotspot and
      considered some of the most biodiverse in the world. The water quality index was
      calculated and some quality parameters were checked to comply with Ecuadorian and
      North American standards for human consumption, preservation of aquatic life and
      irrigation. Four samplings were carried out in six stations covering the entire
      length of the Yacuambi river. Several parameters were analyzed: pH, conductivity,
      dissolved oxygen, temperature, color, phosphates, nitrite, nitrate, biochemical
      oxygen demand, chemical oxygen demand, total solids, turbidity, metals (Ba, Cd,
      Cr, Pb, As and Hg), pesticides and fecal coliforms. The water quality in the
      Yacuambi river was good and medium according to the classification of the Water
      Quality Index. However, it was unsuitable for human consumption, preservation of
      aquatic life and irrigation according to Ecuadorian and North American standards.
      Arsenic, color and fecal coliforms exceeded the limits for human consumption in
      all samples tested. Thresholds of preservation of aquatic life were exceeded in
      all samples in the case of Pb and in some samples for As, pH, nitrite and
      nitrate. Arsenic and fecal coliforms made Yacuambi river waters unsuitable for
      irrigation.

PMID- 29573692
TI  - Long-term trends in submicron particle concentrations in a metropolitan area of
      the northeastern United States.
AB  - Significant changes in emission sources have occurred in the northeastern United
      States over the past decade, due in part to the implementation of emissions
      standards, the introduction and addition of abatement technologies for road
      transport, changes in fuel sulfur content for road and non-road transport, as
      well as economic impacts of a major recession and differential fuel prices. These
      changes in emission scenarios likely affected the concentrations of airborne
      submicron particles. This study investigated the characteristics of 11-500nm
      particle number concentrations and their size spectra in Rochester, NY during the
      past 15years (2002 to 2016). The modal structure, diurnal, weekly and monthly
      patterns of particle number concentrations are analyzed. Long-term trends are
      quantified using seasonal-trend decomposition procedures based on "Loess", Mann
      Kendall regression with Theil-Sen slope and piecewise regression. Particle
      concentrations underwent significant (p<0.05) downward trends. An annual decrease
      of -323particles/cm3/y (-4.6%/y) was estimated for the total particle number
      concentration using Theil-Sen analysis. The trends were driven mainly by the
      decrease in particles in the 11-50nm range (-181particles/cm3/y; -4.7%/y). Slope
      changes were investigated annually and seasonally. Piecewise regression found
      different slopes for different portions of the overall period with the strongest
      declines between 2005 and 2011/2013, followed by small upward trends between 2013
      and 2016 for most size bins, possibly representing increased vehicular traffic
      after the recovery from the 2008 recession.

PMID- 29573693
TI  - Alleviation of heavy metal phytotoxicity in sewage sludge by vermicomposting with
      additive urban plant litter.
AB  - The handling of sewage sludge (SS) and urban plant litter (UPL) has become an
      important concern. Immobilizing heavy metals (HMs) is regarded as a necessary
      process for recycling SS in agriculture and forestry. Here, HM removal and HM
      phytotoxicity in SS during vermicomposting with different additive UPLs was
      investigated. The results show that vermicomposting with additive UPL
      significantly reduced the content of HMs, and increased organic carbon content
      and the proportion of macroaggregates in SS. This process also significantly
      immobilized HMs by mainly transforming extractable and reducible HMs into
      residual products. The litters of Dracontomelon duperreanum and Bauhinia purpurea
      increased oxidizable HMs in SS and the accumulation capacity of HMs of earthworms
      during vermicomposting. The Cd content in vermicomposts with the B. purpurea
      litter addition was decreased by 31% relative to the initial SS. Maize in
      vermicomposts with UPL additions, especially with B. purpurea litter, exhibited
      significan5tly higher seed germination rates, seedling biomass, root activity,
      and a lower accumulation of HMs than in SS compost without UPL additions. These
      results suggest that vermicomposting with additive UPL can alleviate the
      phytotoxicity of HMs in SS and provides a new method for simultaneously recycling
      SS and UPL.

PMID- 29573694
TI  - Differences in N loading affect DOM dynamics during typhoon events in a forested
      mountainous catchment.
AB  - The dissolved organic matter (DOM) and nutrient dynamics in small mountainous
      rivers (SMRs) strongly depend on hydrologic conditions, and especially on extreme
      events. Here, we investigated the quantity and quality of DOM and inorganic
      nutrients during base-flow and typhoon events, in a chronically N-saturated
      mainstream and low N-loaded tributaries of a forested small mountainous reservoir
      catchment in Taiwan. Our results suggest that divergent transport mechanisms were
      triggered in the mainstream vs. tributaries during typhoons. The mainstream DON
      increased from 3.4 to 34.7% of the TDN pool with a static DOC:NO3-N ratio and
      enhanced DOM freshness, signalling a N-enriched DOM transport. Conversely, DON
      decreased from 46 to 6% of the TDN pool in the tributaries and was coupled with a
      rapid increase of the DOC:NO3-N ratio and humified DOM signals, suggesting the
      DON and DOC were passively and simultaneously transported. This study confirmed
      hydrology and spatial dimensions being the main drivers shaping the composition
      and concentration of DOM and inorganic nutrients in small mountainous catchments
      subject to hydrologic extremes. We highlighted that the dominant flow paths
      largely controlled the N-saturation status and DOM composition within each sub
      catchment, the effect of land-use could therefore be obscured. Furthermore, N
      saturation status and DOM composition are not only a result of hydrologic
      dynamics, but potential agents modifying the transport mechanism of solutes
      export from fluvial systems. We emphasize the importance of viewing elemental
      dynamics from the perspective of a terrestrial-aquatic continuum; and of taking
      hydrologic phases and individual catchment characteristics into account in water
      quality management.

PMID- 29573695
TI  - Mercury bioaccumulation and its toxic effects in rats fed with methylmercury
      polluted rice.
AB  - Recent evidence indicated that methylmercury (MeHg) contaminated rice can be a
      significant source of MeHg human exposure, but the health implications are not
      known. The objective of this study was to study the kinetics, speciation, and
      effects of MeHg contaminated rice using a rat model. Five groups of adult Sprague
      Dawley rats (n=10 in each group) were fed control rice, low (10ng/g MeHg) and
      high (25ng/g MeHg) MeHg contaminated rice. Two groups of the positive control
      were fed control rice spiked with the same levels of MeHgCl. Short-term exposure
      to low level of spiked MeHgCl stimulated the growth of male rats while long-term
      exposure to spiked MeHgCl inhibited the growth in female rats. There was no
      temporal variation of total mercury (THg) concentrations in the rat fecal samples
      from each group, and the THg concentrations significantly correlated with the
      inorganic Hg concentrations in the feeding rice. There were significant
      differences in the accumulation of THg and MeHg among different groups and
      different organs. THg and MeHg concentrations in the kidney were the highest
      among the organs examined. The blood and brain had high percentages of THg as
      MeHg, which indicates that MeHg can easily pass through the blood-brain barrier
      and has a high affinity for brain tissue. Exposure to rice containing 25ng/g MeHg
      decreased antioxidant function and damaged the nervous system in rats, but no
      significant effects were found in the group fed with rice containing 10ng/g MeHg.
      MeHgCys in rice is less toxic than spiked MeHgCl to rats. The toxicity of MeHg
      both decided by its concentration and speciation.

PMID- 29573696
TI  - Low omega-6/omega-3 ratio in a maternal protein-deficient diet promotes histone-3
      changes in progeny neural cells and favors leukemia inhibitory factor
      genetranscription.
AB  - Omega-3 (n-3) fatty acids modulate epigenetic changes critical to genesis and
      differentiation of neural cells. Conversely, maternal protein-malnutrition can
      negatively modify these changes. This study investigated whether a low n-6/n-3
      ratio in a maternal diet could favor histone-3 (H3) modifications, gene
      transcription and differentiation in the offspring neural cells even under
      protein-deficiency. Female rats fed a control (Ct), or 3 types of multideficient
      diets differing in protein levels or linoleic/alpha-linolenic fatty acid ratios
      (RBD, RBD-C, RBD-SO) from 30 days prior to mating and during pregnancy. Cerebral
      cortex tissue and cortical cultures of progeny embryonic neurons and postnatal
      astrocytes were analyzed. H3K9 acetylation and H3K27 or H3K4 di-methylation
      levels were assessed by flow cytometry and/or immunocytochemistry. In astrocyte
      cultures and cortical tissue, the GFAP protein levels were assessed. Glial
      derived neurotrophic factor (GDNF) and leukemia inhibitory factor (LIF) gene
      expression were evaluated in the cortical tissue. GFAP levels were similar in
      astrocytes of Ct, RBD and RBD-C, but 65% lower in RBD-SO group. Higher levels of
      H3K9Ac were found in the neurons and H3K4Me2 in the astrocytes of the RBD group.
      No intergroup difference in the cortical GDNF mRNA expression or the H3K27Me2
      levels in astrocytes was detected. LIF mRNA levels were higher in the RDB
      (P=.002) or RBD-C (P=.004) groups than in the control. The findings indicate the
      importance of dietary n-3 availability for the brain, even under a protein
      deficient condition, inducing Histone modifications and increasing LIF gene
      transcription, involved in neural cell differentiation and reactivity.

PMID- 29573697
TI  - Changes in total knee arthroplasty design affect in-vivo kinematics in a
      redesigned total knee system: A fluoroscopy study.
AB  - BACKGROUND: Journey II Bi-Cruciate-Stabilized knee system was designed to
      overcome the complications of Journey Bi-Cruciate-Stabilized, including ilio
      tibial band inflammation and episodes of dislocation. The purpose of this study
      was to assess differences in knee kinematics between the first and second
      generation design by means of video-fluoroscopy. Re-designed prosthesis in-vivo
      kinematics was analyzed during activities of daily living and results were
      eventually compared with those of the previous system, as reported in a
      previously published study. It was hypothesized that changes in components'
      design influences replaced knee's kinematic patterns. METHODS: Sixteen patients
      (3 males, 13 females) implanted with the redesigned prosthesis were assessed by
      video-fluoroscopy during stair-climbing, chair-rising and leg-extension at 8
      months of follow-up. Patterns of axial rotation and antero-posterior motion of
      the medial and lateral femoral condyles were obtained. Range of Motion and
      International Knee Society Score were recorded pre- and post-operatively. Student
      t-tests were applied to compare the mean of each interesting variables. FINDINGS:
      The comparison of the kinematics of the two designs revealed similar patterns of
      axial rotation, with progressive femoral external rotation in flexion and reduced
      absolute values of displacement for the new system. Reduced posterior
      displacements of the medial and lateral condyles were observed in Journey II
      patients. In terms of absolute location, the lateral condyle in the redesigned
      prosthesis showed a more anterior position on the tibial-baseplate embedded
      coordinate system at maximal flexion. INTERPRETATION: Design changes in the
      recently-introduced total knee system contributed to modify its in-vivo knee
      kinematics as demonstrated by video-fluoroscopy.

PMID- 29573698
TI  - Underdetermined blind separation of three-way fluorescence spectra of PAHs in
      water.
AB  - In this work, underdetermined blind decomposition method is developed to
      recognize individual components from the three-way fluorescent spectra of their
      mixtures by using sparse component analysis (SCA). The mixing matrix is estimated
      from the mixtures using fuzzy data clustering algorithm together with the
      scatters corresponding to local energy maximum value in the time-frequency
      domain, and the spectra of object components are recovered by pseudo inverse
      technique. As an example, using this method three and four pure components
      spectra can be blindly extracted from two samples of their mixture, with
      similarities between resolved and reference spectra all above 0.80. This work
      opens a new and effective path to realize monitoring PAHs in water by three-way
      fluorescence spectroscopy technique.

PMID- 29573699
TI  - Spectral and physicochemical properties of difluoroboranyls containing N,N
      dimethylamino group studied by solvatochromic methods.
AB  - The solvatochromism of the dyes was analyzed based on the four-parameter scale
      including: polarizability (SP), dipolarity (SdP), acidity (SA) and basicity (SB)
      parameters by method proposed by Catalan. The change of solvent to more polar
      caused the red shift of absorption and fluorescence band position. The frequency
      shifts manifest the change in the dipole moment upon excitation. The ground-state
      dipole moment of the difluoroboranyls was estimated based on changes in molecular
      polarization with temperature. Moreover, the Stokes shifts were used to calculate
      the excited state dipole moments of the dyes. For the calculation, the ground
      state dipole moments and Onsager cavity radius were also determined theoretically
      using density functional theory (DFT). The experimentally determined excited
      state dipole moments for the compounds are higher than the corresponding ground
      state values. The increase in the dipole moment is described in terms of the
      nature of the excited state.

PMID- 29573700
TI  - A facile fluorescent "turn-off" method for sensing paraquat based on pyranine
      paraquat interaction.
AB  - Development of a technically simple yet effective method for paraquat (PQ)
      detection is of great importance due to its high clinical and environmental
      relevance. In this study, we developed a pyranine-based fluorescent "turn-off"
      method for PQ sensing based on pyranine-PQ interaction. We investigated the
      dependence of analytical performance of this method on the experimental
      conditions, such as the ion strength, medium pH, and so on. Under the optimized
      conditions, the method is sensitive and selective, and could be used for PQ
      detection in real-world sample. This study essentially provides a readily
      accessible fluorescent system for PQ sensing which is cheap, robust, and
      technically simple, and it is envisaged to find more interesting clinical and
      environmental applications.

PMID- 29573701
TI  - Behavioral evidence suggestive of frontal lobe pathology in the amnesic H.M.
AB  - From the earliest published reports, Henry Gustav Molaison-who until his death in
      2008 was known simply by his initials H.M.-was characterized as having a profound
      anterograde amnesia subsequent to mid temporal lobe resection, and that this
      amnestic condition was uncomplicated by other cognitive or behavioral
      impairments. Post-mortem neuropathological examination has detected-in addition
      to the expected temporal lobe lesions-previously unreported frontal lobe and
      white matter pathology, inviting questions concerning the behavioral and
      cognitive consequences that might result from such lesions. The purpose of this
      article is to recount published descriptions of a range of anomalous behaviors by
      H.M. that can not be explained by the memory impairments typically associated
      with anterograde amnesia, to counter previous claims that these behaviors are
      attributable to amygdalar damage, and to advance the interpretation that these
      behaviors are instead consistent with well-documented effects of frontal lobe
      pathology. Transcripts of interviews with H.M. which feature disjointed, often
      contradictory, and arguably confabulatory responses are presented in support of
      this argument.

PMID- 29573702
TI  - Changes in brain connectivity following exposure to bilateral eye movements.
AB  - The present research assessed how engaging in bilateral eye movements influences
      brain activity. Participants had their resting-state brain activity recorded with
      electroencephalography (EEG) before and after they performed 30 s of bilateral
      eye movements or a center-control manipulation. We assessed differences in change
      scores for absolute power and coherence between the eye-movement and center
      control conditions. A main effect for handedness was present for EEG power in the
      theta and beta frequency bands, with inconsistent-handed participants displaying
      a greater increase than consistent-handed participants in both frequency bands.
      For theta, the increase in power for inconsistent handers was specific to
      participants in the bilateral eye-movement condition, whose increase in theta
      power exceeded the increase in theta power for consistent-handed participants
      regardless of condition. In contrast, for coherence, a main effect for condition
      was present for the delta frequency band, with participants in the control
      condition exhibiting a significant drop in posterior delta coherence pre to post.
      We suggest that the maintenance of posterior delta coherence over time may be an
      important factor in sustaining attention. Further, the malleability of EEG power
      for inconsistent-handed participants reveals the importance of individual
      differences variables in the potential for behavioral manipulations to change
      brain activity.

PMID- 29573703
TI  - N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke
      extract in lung Calu-3 cells.
AB  - Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are lethal
      pulmonary diseases. Cigarette consumption is the main cause for development of
      COPD, while CF is produced by mutations in the CFTR gene. Although these diseases
      have a different etiology, both share a CFTR activity impairment and
      proinflammatory state even under sterile conditions. The aim of this work was to
      study the extent of the protective effect of the antioxidant N-acetylcysteine
      (NAC) over the proinflammatory state (IL-6 and IL-8), oxidative stress (reactive
      oxygen species, ROS), and CFTR levels, caused by Cigarette Smoke Extract (CSE) in
      Calu-3 airway epithelial cells. CSE treatment (100 ug/ml during 24 h) decreased
      CFTR mRNA expression and activity, and increased the release of IL-6 and IL-8.
      The effect on these cytokines was inhibited by N-acetyl cysteine (NAC, 5 mM) or
      the NF-kB inhibitor, IKK-2 (10 uM). CSE treatment also increased cellular and
      mitochondrial ROS levels. The cellular ROS levels were normalized to control
      values by NAC treatment, although significant effects on mitochondrial ROS levels
      were observed only at short times (5') and effects on CFTR levels were not
      observed. In addition, CSE reduced the mitochondrial NADH-cytochrome c
      oxidoreductase (mCx I-III) activity, an effect that was not reverted by NAC. The
      reduced CFTR expression and the mitochondrial damage induced by CSE could not be
      normalized by NAC treatment, evidencing the need for a more specific reagent. In
      conclusion, CSE causes a sterile proinflammatory state and mitochondrial damage
      in Calu-3 cells that was partially recovered by NAC treatment.

PMID- 29573704
TI  - The uremic toxin hippurate promotes endothelial dysfunction via the activation of
      Drp1-mediated mitochondrial fission.
AB  - The accumulation of uremic toxins in chronic kidney disease (CKD) induces
      inflammation, oxidative stress and endothelial dysfunction, which is a key step
      in atherosclerosis. Accumulating evidence indicates increased mitochondrial
      fission is a contributing mechanism for impaired endothelial function. Hippurate,
      a uremic toxin, has been reported to be involved in cardiovascular diseases.
      Here, we assessed the endothelial toxicity of hippurate and the contribution of
      altered mitochondrial dynamics to hippurate-induced endothelial dysfunction.
      Treatment of human aortic endothelial cells with hippurate reduced the expression
      of endothelial nitric oxide synthase (eNOS) and increased the expression of
      intercellular cell adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF).
      The mechanisms of hippurate-induced endothelial dysfunction in vitro depended on
      the activation of Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission
      and overproduction of mitochondrial reactive oxygen species (mitoROS). In a rat
      model in which CKD was induced by 5/6 nephrectomy (CKD rat), we observed
      increased oxidative stress, impaired endothelium-dependent vasodilation, and
      elevated soluble biomarkers of endothelial dysfunction (ICAM-1 and vWF).
      Similarly, endothelial dysfunction was identified in healthy rats treated with
      disease-relevant concentrations of hippurate. In aortas of CKD rats and hippurate
      treated rats, we observed an increase in Drp1 protein levels and mitochondrial
      fission. Inhibition of Drp1 improved endothelial function in both rat models.
      These results indicate that hippurate, by itself, can cause endothelial
      dysfunction. Increased mitochondrial fission plays an active role in hippurate
      induced endothelial dysfunction via an increase in mitoROS.

PMID- 29573706
TI  - Versatile ruthenium(II) dye towards blue-light emitter and dye-sensitizer for
      solar cells.
AB  - A versatile Ru(II) complex bearing an anthracene moiety was synthesized in our
      search for suitable compounds towards efficient molecular devices. The new
      engineered dye, cis-[Ru(dcbH2)(NCS)2(mbpy-anth)] (dcbH2=2,2'-bipyridyl-4,4'
      dicarboxylic acid, mbpy-anth=4-[N-(2-anthryl)carbamoyl]-4'-methyl-2,2'
      bipyridine), exhibits a blueish emission in a vibronically structured spectrum
      ascribed to the fluorescence of a 1LCAnth (ligand centered) excited state in the
      anthracene and has a potential to be exploited in the fields of smart lighting
      and displays. This complex was also employed in dye-sensitized solar cells with
      fairly efficient solar energy conversion with the use of self-assembled TiO2
      compact layers beneath the TiO2 mesoporous film to prevent meso-TiO2/dye back
      reactions. Further photoelectrochemical investigations through incident photon-to
      current efficiency and electrochemical impedance spectra showed that the all-nano
      TiO2 compact layer acts as contact layers that increase the electron harvesting
      in the external circuit, enhancing efficiencies up to 50%.

PMID- 29573705
TI  - Peroxidasin-mediated crosslinking of collagen IV is independent of NADPH
      oxidases.
AB  - Collagen IV is a major component of the basement membrane in epithelial tissues.
      The NC1 domains of collagen IV protomers are covalently linked together through
      sulfilimine bonds, the formation of which is catalyzed by peroxidasin. Although
      hydrogen peroxide is essential for this reaction, the exact source of the oxidant
      remains elusive. Members of the NOX/DUOX NADPH oxidase family are specifically
      devoted to the production of superoxide and hydrogen peroxide. Our aim in this
      study was to find out if NADPH oxidases contribute in vivo to the formation of
      collagen IV sulfilimine crosslinks. We used multiple genetically modified in vivo
      model systems to provide a detailed assessment of this question. Our data
      indicate that in various peroxidasin-expressing tissues sulfilimine crosslinks
      between the NC1 domains of collagen IV can be readily detected in the absence of
      functioning NADPH oxidases. We also analyzed how subatmospheric oxygen levels
      influence the collagen IV network in collagen-producing cultured cells with rapid
      matrix turnover. We showed that collagen IV crosslinks remain intact even under
      strongly hypoxic conditions. Our hypothesis is that during collagen IV network
      formation PXDN cooperates with a NOX/DUOX-independent H2O2 source that is
      functional also at very low ambient oxygen levels.

PMID- 29573707
TI  - A novel tetrahydroisoquinoline (THIQ) analogue induces mitochondria-dependent
      apoptosis.
AB  - Lung cancer continues to be a leading cause of cancer-related death worldwide,
      with non-small cell lung cancer (NSCLC) accounting for more than 80% of lung
      cancer cases. Current therapies for NSCLC have only limited effect and treatment
      resistance develops rapidly. In a previous study, we have shown that C1
      phenylethynyl tetrahydroisoquinoline (THIQ) analogue 4 has anti-proliferative
      activity against PC3 human prostate cancer cells. However, this anticancer effect
      was achieved with relatively high IC50 in A549 lung cancer cells. To improve the
      potency of the drug, in the present study, a series of novel THIQ analogues
      (analogues 5a-d) were prepared by using an oxidative C-H functionalization
      strategy, and their potential anticancer activities on A549 lung cancer cells
      were investigated. Among these analogues, analogue 5c can markedly inhibit A549
      cell proliferation in a dose-dependent manner with a reasonable IC50 of 14.61 +/-
      1.03 MUM. This effect was mediated by analogue 5c-induced G0/G1 phase arrest and
      cell apoptosis. Treatment with analogue 5c was shown to induce reactive oxygen
      species (ROS) accumulation, disruption of mitochondrial membrane potential,
      reduction of glutathione, elevation of intracellular calcium ion (Ca2+), and
      activation of Caspase-3. Furthermore, analogue 5c can lead to DNA double-strand
      break and the activation of p53 pathway in A549 cells. In conclusion, the
      oxidative C-H functionalization strategy to generate analogue 5c could improve
      the drug anticancer efficacy by inducing mitochondria-dependent apoptosis in A549
      cells.

PMID- 29573708
TI  - Determinants of hospitalization and length of stay among people with dementia -
      An analysis of statutory health insurance claims data.
AB  - OBJECTIVE: Dementia is a crucial challenge in acute care hospitals. Using a
      retrospective claims data cohort, this paper explores dementia patients' acute
      hospitalization rates, risk factors, and length of stay. METHODS: The study used
      claims data from AOK PLUS, the largest statutory health insurance service (SHI)
      in Saxony, a federal state of Germany. The analysis included 61,239 people with
      dementia and 183,477 control subjects, all 65 years and older. Control subjects
      were age, gender, and regionally matched in a 1:3 ratio. Negative binomial hurdle
      regression was used to compare differences in hospitalization for the year 2014.
      RESULTS: People with dementia had 1.49 times higher adjusted odds of being
      hospitalized at least once (95% confidence interval [CI], 1.46-1.52). Among those
      individuals hospitalized at least once, dementia increased the number of
      readmissions by 18% (95% CI, 1.15-1.20). Dementia patients also had a 1.74 times
      higher odds for at least one emergency admission compared to individuals without
      dementia (95% CI, 1.70-1.78). Dementia patients' admission risk factors included
      having care dependency, being recently diagnosed with dementia and living outside
      a metropolitan region. The increased length of stay for people with dementia per
      year was mainly attributable to higher admission rates. CONCLUSIONS: Dementia
      patients are at higher risk for hospitalization, especially if they live outside
      the metropolitan region. Healthcare systems need to respond to the challenges
      resulting from the predicted demographic developments and increasing burden of
      dementia in the general population.

PMID- 29573709
TI  - Aquatic plants: Test species sensitivity and minimum data requirement evaluations
      for chemical risk assessments and aquatic life criteria development for the USA.
AB  - Phytotoxicity results from the publicly-available ECOTOX database were summarized
      for 20 chemicals and 188 aquatic plants to determine species sensitivities and
      the ability of a species-limited toxicity data set to serve as a surrogate for a
      larger data set. The lowest effect concentrations reducing the sublethal response
      parameter of interest by 50% relative to the controls (EC50) usually varied
      several orders of magnitude for the 119 freshwater and 69 saltwater plants
      exposed to the same test chemicals. Generally, algae were more sensitive than
      floating and benthic species but inter-specific differences for EC50 values were
      sometimes considerable within and between phyla and no consistently sensitive
      species was identified for the morphologically-diverse taxa. Consistent
      equivalencies of the phytotoxicity databases for freshwater-saltwater plants and
      floating-benthic macrophyte species were not demonstrated. Two species
      sensitivity distribution plots (SSDs) were constructed for each of the 20
      chemicals, one based on all available phytotoxicity information (range = 10-76
      test species) and another based on information for only five species recommended
      for pesticide hazard evaluations. HC5 values (hazardous concentration to 5% of
      test species) estimated from the two SSDs usually differed four-fold or less for
      the same chemical. HC5 values for the five species were often conservative
      estimates of HC5 values for the more species-populated data sets. Consequently,
      the collective response of the five test species shows promise as an interim
      aquatic plant minimum data requirement for aquatic life criteria development. In
      contrast, the lowest EC50 values for the five species usually were greater than
      HC5 values for the same test chemicals, a finding important to criteria
      supporting Final Plant Values. The conclusions may differ for comparisons based
      on other test chemicals, test species, response parameters and calculations.

PMID- 29573710
TI  - Expression of the human gene CYP1A2 enhances tolerance and detoxification of the
      phenylurea herbicide linuron in Arabidopsis thaliana plants and Escherichia coli.
AB  - The phenylurea herbicide, linuron (LIN), is used to control various types of
      weeds. Despite its efficient role in controlling weeds, it presents a persistent
      problem to the environment. In the current study, phytoremediation properties of
      transgenic CYP1A2 Arabidopsis thaliana plants to LIN were assessed. CYP1A2 gene
      was firstly cloned and expressed in bacteria before proceeding to plants. In
      presence of LIN, The growth of CYP1A2 expressing bacteria was superior compared
      to control bacteria transformed with the empty bacterial expression vector
      pET22b(+). No clear morphological changes were detected on CYP1A2 transgenic
      plants. However, significant resistance to LIN herbicide application either via
      spraying the foliar parts of the plant or via supplementation of the herbicide in
      the growth medium was observed for CYP1A2 transformants. Plant growth assays
      under LIN stress provide strong evidence for the enhanced capacity of transgenic
      lines to grow and to tolerate high concentrations of LIN compared to control
      plants. HPLC analyses showed that detoxification of LIN by bacterial extracts
      and/or transgenic plant leaves is improved as compared to the corresponding
      controls. Our data indicate that over expression of the human CYP1A2 gene
      increases the phytoremediation capacity and tolerance of Arabidopsis thaliana
      plants to the phenylurea herbicide linuron.

PMID- 29573711
TI  - Estimating the contribution of bacteriophage to the dissemination of antibiotic
      resistance genes in pig feces.
AB  - The transfer of antibiotic resistance genes (ARGs) in the environment is a threat
      to both human and animal health. However, the contribution of bacteriophages to
      the dissemination of resistance genes via transduction is rarely explored. In
      this study, we screened pig feces from three commercial farms in China for 32
      clinically relevant ARG types to assess the presence of the ARG population in
      bacteria and bacteriophage and further to estimate the contribution of
      bacteriophages to the dissemination of antibiotic resistance. We found that
      bacteriophage DNA contained 35.5% of the target ARG types and sul1, blaTEM and
      ermB were found in 100% of the phage DNA samples. The most abundant genes in the
      bacterial population were ermB and fexA whereas ermB was the most abundant in
      bacteriophage. In contrast, floR was the least abundant ARG in both populations.
      Also, the ratio index of the abundance of ARGs in bacteriophage and bacteria was
      firstly used in this study as an estimator of bacteriophage ability to transmit
      ARGs. The ratio for qnrA was the greatest (about 10-1) and differed from the most
      abundant bacteriophage ARG ermB. In addition, fexA had the lowest ratio value
      (about 10-6) and not floR. These results illustrate that ARGs abundance and
      detection rates used alone probably be not suitable for comprehensively judging
      the contribution of bacteriophage to the dissemination of antibiotic resistance.
      A more suitable model is the application of three indices; occurrence rate,
      absolute abundance in bacteriophage and the ratio value as warning and monitoring
      tools for environmental ARG assessments in bacteriophages.

PMID- 29573712
TI  - Urinary bisphenol analogues and triclosan in children from south China and
      implications for human exposure.
AB  - Bisphenols and triclosan (TCS) are widely used in consumer products. However,
      knowledge on human exposure to these anthropogenic chemicals has remained limited
      in China, especially for children. In this study, concentrations of seven
      bisphenols and TCS were determined in 283 urine samples collected from South
      China children aged between 3 and 11 years old. Bisphenol A (BPA), bisphenol S
      (BPS) and TCS were frequently detected in urine samples, with a detection rate of
      93%, 89%, and 95%, respectively. Urinary concentrations of Sigma7BPs (the sum
      concentrations of the seven bisphenols) ranged from 0.43 to 31.5 MUg/L, with a
      median value of 0.91 MUg/L, while TCS concentrations ranged from < limit of
      quantification to 21.9 MUg/L (median: 0.21 MUg/L). BPA was the predominant
      analogue (median: 0.35 MUg/L), accounting for 49.8% of Sigma7BPs. The urinary BPA
      concentrations in children from Guangzhou were significantly greater than those
      from Shenzhen. Correlation analysis suggested that multiple exposure sources to
      South China children likely existed for BPA, BPS, and TCS. Age, but not gender,
      was negatively associated with urinary residues of BPA and BPS (p < 0.05) and
      positively with TCS concentrations (p < 0.05). The estimated daily intake of
      Sigma7BPs (23.9 ng/kg bw/day) or TCS (5.63 ng/kg bw/day) was below the tolerant
      reference dose of BPA, indicating no considerable health hazard to South China
      children.

PMID- 29573713
TI  - River otters (Lontra canadensis) "trapped" in a coastal environment contaminated
      with persistent organic pollutants: Demographic and physiological consequences.
AB  - Productive coastal and estuarine habitats can be degraded by contaminants
      including persistent organic pollutants (POPs) such as PCBs, dioxins, and
      organochlorine insecticides to the extent of official designation as contaminated
      sites. Top-predatory wildlife may continue to use such sites as the habitat often
      appears suitable, and thus bioaccumulate POPs and other contaminants with
      potential consequences on their health and fitness. Victoria and Esquimalt
      harbours are located on southern Vancouver Island, British Columbia (BC) and are
      federally designated contaminated sites due mainly to past heavy industrial
      activities, such as from shipyards and sawmills. We collected scat samples from
      river otters (Lontra canadensis) throughout an annual cycle, and combined
      chemical analysis with DNA genotyping to examine whether the harbour areas
      constituted a contaminant-induced ecological trap for otters. We confirmed
      spatial habitat use by radio telemetry of a subsample of otters. Fifteen percent
      of otter scat contained PCB concentrations exceeding levels considered to have
      adverse effects on the reproduction of mink (Neovison vison), and there were
      significant positive correlations between concentrations of PCBs and of thyroid
      (T3) and sex (progesterone) hormones in fecal samples. Radio telemetry data
      revealed that otters did not show directional movement away from the harbours,
      indicating their inability to recognize the contaminated site as a degraded
      habitat. However, analysis and modeling of the DNA genotyping data provided no
      evidence that the harbour otters formed a sink population and therefore were in
      an ecological trap. Despite the highly POP-contaminated habitat, river otters did
      not appear to be adversely impacted at the population level. Our study
      demonstrates the value of combining chemical and biological technologies with
      ecological theory to investigate practical conservation problems.

PMID- 29573715
TI  - Concentrations and congener profiles of chlorinated paraffins in domestic
      polymeric products in China.
AB  - Chlorinated paraffins (CPs) are widely used in domestic polymeric products as
      plasticizers and fire retardants. In this study, concentrations and congener
      profiles of short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs)
      were investigated in domestic polymeric products, including plastics, rubber and
      food packaging in China. The average concentrations of SCCPs in polyethylene
      terephthalate (PET), polypropylene (PP), polyethylene (PE) and food packaging
      were 234, 3968, 150 and 188 ng/g, respectively and the corresponding average
      concentrations of MCCPs in these samples were 37.4, 2537, 208 and 644 ng/g,
      respectively. The concentrations of CPs in rubber and polyvinylchloride (PVC)
      were significantly higher than in other matrices. The highest concentrations of
      SCCPs and MCCPs were found in a PVC cable sheath with 191 mg/g and 145 mg/g,
      respectively. Congener group profiles analysis indicated C11- and C13-congener
      groups were predominant in carbon homologues of SCCPs, and C14-congener groups
      were predominant in MCCPs. High levels of SCCPs and MCCPs in domestic polymeric
      products implied that they might be a significant source to the environment and
      human exposure.

PMID- 29573714
TI  - Integrated assessment of persistent toxic substances in sediments from Masan Bay,
      South Korea: Comparison between 1998 and 2014.
AB  - Complexity of anthropogenic influences on coastal ecosystems necessitates use of
      an integrated assessment strategy for effective interpretation and subsequent
      management. In this study a multiple lines of evidence (LOE) approach for
      sediment assessment, that combined use of chemistry, toxicity, and benthic
      community structure in the sediment quality triad was used to assess
      spatiotemporal changes and potential risks of persistent toxic substances (PTSs)
      in sediments of Masan Bay highlighting "long-term changes" between 1998 and 2014.
      Specific target objectives encompassed sedimentary PTSs (PAHs, alkylphenols
      (APs), and styrene oligomers), potential aryl hydrocarbon receptor (AhR; H4IIE
      luc assay)- and estrogen receptor (ER; MVLN assay)-mediated activities, and
      finally several ecological quality (EcoQ) indices of benthic community structure.
      Concentrations of target PTSs in Masan Bay sediments were generally less by half
      in 2014 compared to those measured in 1998. Second, AhR-mediated potencies in
      sediments also decreased during this time interval, whereas ER-mediated potencies
      increased (+3790%), indicating that there has been substantial ongoing, input of
      ER agonists over the past 16 years. Potency balance analysis revealed that only
      3% and 22% of the AhR- and ER-mediated potencies could be explained by identified
      known chemicals, such as PAHs and APs, respectively. This result indicated that
      non-targeted AhR and ER agonists had a considerable presence in the sediments
      over time. Third, EcoQ indices tended to reflect PTSs contamination in the
      region. Finally, ratio-to-mean values obtained from the aforementioned three LOEs
      indicated that quality of sediments from the outer region of the bay had recovery
      more during the period of 16-years than did the inner region. Overall, the
      results showed that even with the progress supported by recent efforts from the
      Korean governmental pollution control, PTSs remain a threat to local ecosystem,
      especially in the inner region of Masan Bay.

PMID- 29573716
TI  - Wi-Fi is an important threat to human health.
AB  - Repeated Wi-Fi studies show that Wi-Fi causes oxidative stress, sperm/testicular
      damage, neuropsychiatric effects including EEG changes, apoptosis, cellular DNA
      damage, endocrine changes, and calcium overload. Each of these effects are also
      caused by exposures to other microwave frequency EMFs, with each such effect
      being documented in from 10 to 16 reviews. Therefore, each of these seven EMF
      effects are established effects of Wi-Fi and of other microwave frequency EMFs.
      Each of these seven is also produced by downstream effects of the main action of
      such EMFs, voltage-gated calcium channel (VGCC) activation. While VGCC activation
      via EMF interaction with the VGCC voltage sensor seems to be the predominant
      mechanism of action of EMFs, other mechanisms appear to have minor roles. Minor
      roles include activation of other voltage-gated ion channels, calcium cyclotron
      resonance and the geomagnetic magnetoreception mechanism. Five properties of non
      thermal EMF effects are discussed. These are that pulsed EMFs are, in most cases,
      more active than are non-pulsed EMFs; artificial EMFs are polarized and such
      polarized EMFs are much more active than non-polarized EMFs; dose-response curves
      are non-linear and non-monotone; EMF effects are often cumulative; and EMFs may
      impact young people more than adults. These general findings and data presented
      earlier on Wi-Fi effects were used to assess the Foster and Moulder (F&M) review
      of Wi-Fi. The F&M study claimed that there were seven important studies of Wi-Fi
      that each showed no effect. However, none of these were Wi-Fi studies, with each
      differing from genuine Wi-Fi in three distinct ways. F&M could, at most conclude
      that there was no statistically significant evidence of an effect. The tiny
      numbers studied in each of these seven F&M-linked studies show that each of them
      lack power to make any substantive conclusions. In conclusion, there are seven
      repeatedly found Wi-Fi effects which have also been shown to be caused by other
      similar EMF exposures. Each of the seven should be considered, therefore, as
      established effects of Wi-Fi.

PMID- 29573717
TI  - Soil contamination and sources of phthalates and its health risk in China: A
      review.
AB  - Phthalates (PAEs) are extensively used as plasticizers and constitute one of the
      most frequently detected organic contaminants in the environment. With the
      deterioration of eco-environment in China during the past three decades, many
      studies on PAE occurrence in soils and their risk assessments have been conducted
      which allow us to carry out a fairly comprehensive assessment of soil PAE
      contamination on a nation-wide scale. This review combines the updated
      information available associated with PAE current levels, distribution patterns
      (including urban soil, rural or agricultural soil, seasonal and vertical
      variations), potential sources, and human health exposure. The levels of PAEs in
      soils of China are generally at the high end of the global range, and higher than
      the grade II limits of the Environmental Quality Standard for soil in China. The
      most abundant compounds, di-n-butyl phthalate (DBP) and di-(2-ethylhexyl)
      phthalate (DEHP), display obvious spatial distribution in different provinces. It
      is noted that urbanization and industrialization, application of plastic film
      (especially plastic film mulching in agricultural soil) and fertilizer are the
      major sources of PAEs in soil. Uptake of PAEs by crops, and human exposure to
      PAEs via ingestion of soil and vegetables are reviewed, with scientific gaps
      highlighted.

PMID- 29573718
TI  - The influence of microplastics and halogenated contaminants in feed on
      toxicokinetics and gene expression in European seabass (Dicentrarchus labrax).
AB  - When microplastics pollute fish habitats, it may be ingested by fish, thereby
      contaminating fish with sorbed contaminants. The present study investigates how
      combinations of halogenated contaminants and microplastics associated with feed
      are able to alter toxicokinetics in European seabass and affect the fish.
      Microplastic particles (2%) were added to the feed either with sorbed
      contaminants or as a mixture of clean microplastics and chemical contaminants,
      and compared to feed containing contaminants without microplastics. For the
      contaminated microplastic diet, the accumulation of polychlorinated biphenyls
      (PCBs) and brominated flame retardants (BFRs) in fish was significantly higher,
      increasing up to 40 days of accumulation and then reversing to values comparable
      to the other diets at the end of accumulation. The significant gene expression
      results of liver (cyp1a, il1beta, gstalpha) after 40 days of exposure indicate
      that microplastics might indeed exacerbate the toxic effects (liver metabolism,
      immune system, oxidative stress) of some chemical contaminants sorbed to
      microplastics. Seabass quickly metabolised BDE99 to BDE47 by debromination,
      probably mediated by deiodinase enzymes, and unlike other contaminants, this
      metabolism was unaffected by the presence of microplastics. For the other PCBs
      and BFRs, the elimination coefficients were significantly lower in fish fed the
      diet with contaminants sorbed to microplastic compared to the other diets. The
      results indicate that microplastics affects liver detoxification and lipid
      distribution, both of which affect the concentration of contaminants.

PMID- 29573719
TI  - Anti-inflammatory activity of mulberrofuran K isolated from the bark of Morus
      bombycis.
AB  - Morus bombycis Koidzumi, commonly known as silkworm mulberry, is a plant
      belonging to family Moraceae. It has been used in Asian countries as a
      traditional medicine for treating hypertension, diabetes, and inflammatory
      disorders. In this study, we isolated eleven compounds from the cortex of M.
      bombycis and evaluated their inhibitory effects on nitric oxide (NO) production
      as an indicator of their anti-inflammatory activities using lipopolysaccharide
      (LPS)-stimulated murine macrophages. Compound 4 showed the most potent inhibitory
      activity on NO production. It was identified as mulberrofuran K (MFK). Anti
      inflammatory activity of MFK was then carried out using LPS-stimulated RAW264.7
      cells. MFK suppressed the production of NO, reactive oxygen species (ROS), and
      proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumor necrosis factor
      alpha (TNF-alpha)) in a concentration-dependent manner. Western blot analysis
      revealed that MFK treatment inhibited expression levels of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2). MFK also inhibited transcriptional
      activation of nuclear factor-kappaB (NF-kappaB) and extracellular-regulated
      kinases (ERK) 1/2 in LPS-stimulated murine macrophages. These results suggest
      that MFK, an anti-inflammatory constituents of M. bombycis cortex, has potential
      as a therapeutic candidates for preventing and treating inflammatory diseases.

PMID- 29573720
TI  - Postpartum blood transfusion and hemorrhage as independent risk factors for
      venous thromboembolism.
AB  - INTRODUCTION: Profuse postpartum hemorrhage (PPH) and red blood cell (RBC)
      transfusion have been suggested to be associated with venous thromboembolic
      events (VTE). However, it is not fully clear if they are independent major risk
      factors. METHODS: Women who gave birth in the Stockholm area between 1999 and
      2002 were those studied, i.e., before the implementation of guidelines for
      thromboprophylaxis in pregnancy. In this population-based cohort study the
      Swedish Medical Birth Registry was linked to the National Discharge Registry and
      to the transfusion database. Cases with VTE were identified as well as the
      patient's transfusion history. The main outcome was an assessment of RBC
      transfusion and PPH as independent risk factors for postpartum thrombosis,
      analyzed in logistic regression models. RESULTS: Out of the 82,376 deliveries, 56
      cases of postpartum VTE were identified (0.70/00). Compared to the control group,
      the risk of VTE increased with the number of RBC transfusions: 1 to 3 units (OR =
      3.3, 95% CI 1.2-8.9) and >3 units (OR = 5.2, 95%CI 1.7-16.1), but PPH was not
      found to be a major risk factor (OR = 1.4, 95% CI 0.5-3.5). Surprisingly, the
      small group treated with plasma in addition to RBC transfusion were not at a
      significantly increased risk (OR = 1.8, 95% CI 0.2-14.0). Preeclampsia and
      placental abruption were major risk factors. CONCLUSION: We found RBC
      transfusion, but not PPH alone, to be an independent risk factor for postpartum
      VTE and propose that it should be included in the thromboprophylaxis algorithm
      for implementation during pregnancy.

PMID- 29573721
TI  - Novel heparin mimetics reveal cooperativity between exosite 2 and sodium-binding
      site of thrombin.
AB  - INTRODUCTION: Thrombin is a primary target of most anticoagulants. Yet,
      thrombin's dual and opposing role in pro- as well as anti- coagulant processes
      imposes considerable challenges in discovering finely tuned regulators that
      maintain homeostasis, rather than disproportionately changing the equilibrium to
      one side. In this connection, we have been studying exosite 2-mediated allosteric
      modulation of thrombin activity using synthetic agents called low molecular
      weight lignins (LMWLs). Although the aromatic scaffold of LMWLs is completely
      different from the polysaccharidic scaffold of heparin, the presence of multiple
      negatively charged groups on both ligands induces binding to exosite 2 of
      thrombin. This work characterizes the nature of interactions between LMWLs and
      thrombin to understand the energetic cooperativity between exosite 2 and active
      site of thrombin. MATERIALS AND METHODS: The thermodynamics of thrombin-LMWL
      complexes was studied using spectrofluorimetric titrations as a function of ionic
      strength and temperature of the buffer. The contributions of enthalpy and entropy
      to binding were evaluated using classic thermodynamic equations. Label-free
      surface plasmon resonance was used to assess the role of sodium ion in LMWL
      binding to thrombin at a fixed ionic strength. RESULTS AND CONCLUSIONS: Exosite 2
      induced conformational change in thrombin's active site is strongly dependent on
      the structure of the ligand, which has consequences with respect to regulation of
      thrombin. The ionic and non-ionic contributions to binding affinity and the
      thermodynamic signature were highly ligand specific. Interestingly, LMWLs display
      preference for the sodium-bound form of thrombin, which supports the existence of
      an energetic coupling between exosite 2 and sodium-binding site of thrombin.

PMID- 29573722
TI  - Systematic review and meta-analysis of the association of combined oral
      contraceptives on the risk of venous thromboembolism: The role of the progestogen
      type and estrogen dose.
AB  - INTRODUCTION: Currently available combined oral contraceptives (COC) reportedly
      increase the risk of venous thromboembolism (VTE). We aimed to quantify this risk
      considering both progestogen type and estrogen dose. MATERIALS AND METHODS:
      PubMed, Embase and LIVIVO were searched for relevant publications until April
      2017. Case-control and cohort studies including healthy women taking COC and
      assessing incident VTE as outcome were selected. Adjusted relative risks (RR)
      with 95% confidence intervals (CI) derived from random effects model using a
      generic inverse-variance approach are reported. RESULTS: Overall, 1,359
      references were identified and 17 studies were included in the meta-analysis. The
      pooled RR of VTE was associated with various COC, with the association depending
      on their respective estrogen dose and progestogen type. Compared to the
      reference, levonorgestrel with 30-40 MUg ethinylestradiol, the overall risk of
      VTE was higher for all other COC. Preparations with desogestrel with 30-40 MUg
      estrogen showed the highest relative risk (RR: 1.46; 95% CI: 1.33-1.59), while
      RRs for drospirenone (30-40 MUg ethinylestradiol) and desogestrel (30-40/20 MUg
      ethinylestradiol) were lower. COC containing gestodene and cyproterone with 30-40
      MUg estrogen showed the lowest risk (RR: 1.27; 95% CI: 1.15-1.41 and RR: 1.29;
      95% CI: 1.12-1.49, respectively). CONCLUSIONS: Compared to levonorgestrel with 30
      40 MUg ethinylestradiol, all COC showed a significantly increased VTE risk. The
      association varied depending on the progestogen type and the dose of estrogen.
      Our results suggest that the prescription of COC with the lowest possible dose of
      ethinylestradiol may help to avoid VTE cases among young, healthy women.

PMID- 29573723
TI  - An integrated metabolomic and proteomic study of toxic effects of Benzo[a]pyrene
      on gills of the pearl oyster Pinctada martensii.
AB  - Benzo[a]pyrene (BaP) is one of the most important polycyclic aromatic
      hydrocarbons (PAHs), which are widely present in the marine environment. Because
      of its teratogenic, mutagenic, and carcinogenic effects on various organisms, the
      toxicity of BaP is of great concern. In this study, we focused on the toxic
      effects of BaP (1 ug/L and 10 ug/L) on gills of the pearl oyster Pinctada
      martensii using combined metabolomic and proteomic approaches. At the metabolome
      level, the high concentration of BaP mainly caused abnormal energy metabolism,
      osmotic regulation and immune response marked by significantly altered
      metabolites in gills. At the proteome level, both concentrations of BaP mainly
      induced signal transduction, transcription regulation, cell growth, stress
      response, and energy metabolism. Overall, the research demonstrated that the
      combination of proteomic and metabolomic approaches could provide a significant
      way to elucidate toxic effects of BaP on P. martensii.

PMID- 29573724
TI  - Tetracycline resistance genes are more prevalent in wet soils than in dry soils.
AB  - This study aimed to reveal the effects of water content on the spread of
      tetracycline resistance genes (TRGs) in the soil. Amendments of four samples with
      different soil water contents, namely 16% (dry soil) and 25% (wet soil), and with
      or without pig manures (PM) were conducted under laboratory conditions.
      Quantitative polymerase chain reaction (q-PCR) results showed that the relative
      abundance of TRGs (tetB, tetC, tetM, tetO, tetT, and tetZ) in the wet soils was
      significantly higher than that in the dry soils whether under fertilization or
      non-fertilization conditions. Moreover, PM application enhanced the relative
      abundance of TRGs. The absolute copies of TRGs did not decline with the decrease
      in 16S rRNA genes in wet soils, implying that most TRGs were probably located in
      facultative anaerobic bacteria. However, cultivable tetracycline-resistant
      bacteria (TRB) in the wet soils were not in line with the q-PCR results, further
      indicating that aerobes might not account for the increases in the relative
      abundance of TRGs. Diversities of aerobic TRB were significantly higher in the
      wet soils than in the dry soils, especially on days 14 and 28. The patterns of
      community structures of aerobic TRB in the wet soils or dry soils containing PM
      were different from those in the dry soils. Together, this study showed that the
      variations in bacterial communities between the wet and dry soils, especially
      reflected in the diversity of aerobic TRB and/or community structure of
      facultative anaerobic TRB, might be an important reason behind the changes in the
      abundance of TRGs.

PMID- 29573725
TI  - Pretilachlor toxicity is decided by discrete photo-acclimatizing conditions:
      Physiological and biochemical evidence from Anabaena sp. and Nostoc muscorum.
AB  - The current study was undertaken to elucidate the impact of the herbicide
      pretilachlor (3 ug ml-1 and 6 ug ml-1) on cyanobacteria, Nostoc muscorum ATCC
      27893 and Anabaena sp. PCC 7120 under three levels of photoacclimatization
      (suboptimum, 25 umol photon m-2 s-1; optimum, 75 umol photon m-2 s-1; and supra
      optimum, 225 umol photon m-2 s-1) by analyzing certain physiological (biomass
      accumulation, photosynthesis, Chl a fluorescence and respiration) and biochemical
      parameters (photosynthetic pigments- chlorophyll a, carotenoids and phycocyanin;
      reactive oxygen species- O2*-, H2O2, lipid peroxidation; antioxidant system-
      superoxide dismutase, peroxidise, catalase and glutathione-S-transferase). The
      light conditioning played the most prominent role in deciding the extent of
      herbicide toxicity on both the tested cyanobacteria as the maximum toxicity was
      observed in suboptimum light acclimatized cyanobacterial cells corroborated by
      the least growth in the same cells. The impact of pretilachlor treatment on
      photosystem II photochemistry viz. phiP0, ?0, phiE0, PIABS, ABS/RC, TR0/RC,
      ET0/RC and DI0/RC was also altered by light acclimatization. The percent rise in
      oxidative stress markers (SOR and H2O2) and consequent lipid peroxidation (MDA
      equivalents) were also highest in suboptimum light acclimatized cells exposed to
      pretilachlor which could not be prospered with compatible antioxidant
      performance. Conversely, supra-optimum light acclimatized cells of both the
      cyanobacteria was found to accelerate the activities of all the studied enzymes
      and thus able to counterbalance the pretilachlor toxicity and supported the
      healthier growth.

PMID- 29573726
TI  - Can chronic exposure to imidacloprid, clothianidin, and thiamethoxam mixtures
      exert greater than additive toxicity in Chironomus dilutus?
AB  - Widespread agricultural use of neonicotinoid insecticides has resulted in
      frequent detection of mixtures of these compounds in global surface waters.
      Recent evidence suggests that neonicotinoid mixtures can elicit synergistic
      toxicity in aquatic insects under acute exposure conditions, however this has not
      been validated for longer exposures more commonly encountered in the environment.
      Therefore, we aimed to characterize the chronic (28-day) toxicity of
      imidacloprid, clothianidin, and thiamethoxam mixtures under different doses and
      mixture ratios to determine if the assumption of synergistic toxicity would hold
      under more environmentally realistic exposure settings. The sensitive aquatic
      insect Chironomus dilutus was used as a representative test species, and
      successful emergence was used as a chronic endpoint. Applying the MIXTOX modeling
      approach, predictive parametric models were fitted using single-compound toxicity
      data and statistically compared to observed toxicity in subsequent mixture tests.
      Imidacloprid-clothianidin, clothianidin-thiamethoxam and imidacloprid
      clothianidin-thiamethoxam mixtures did not significantly deviate from
      concentration-additive toxicity. However, the cumulative toxicity of the
      imidacloprid-thiamethoxam mixture deviated from the concentration-additive
      reference model, displaying dose-ratio dependent synergism and resulting in up to
      a 10% greater reduction in emergence from that predicted by concentration
      addition. Furthermore, exposure to select neonicotinoid mixtures above 1.0 toxic
      unit tended to shift sex-ratios toward more male-dominated populations. Results
      indicate that, similar to acute exposures, the general assumption of joint
      additivity cannot adequately describe chronic cumulative toxicity of all
      neonicotinoid mixtures. Indeed, our observations of weak synergism and sex-ratio
      shifts elicited by some mixture combinations should be considered in water
      quality guideline development and environmental risk assessment practices for
      neonicotinoid insecticides, and explored in further investigations of the effects
      of neonicotinoid mixtures on aquatic communities.

PMID- 29573727
TI  - A novel electrochemical sensor based on silver/halloysite nanotube/molybdenum
      disulfide nanocomposite for efficient nitrite sensing.
AB  - In the present study, the silver/halloysite nanotube/molybdenum disulfide
      (Ag/HNT/MoS2) nanocomposite was successfully synthesized. For this purpose, the
      lumen of HNTs was firstly modified by silver to generate Ag nanorods via chemical
      process and then the MoS2 layers deposited on the Ag/HNT nanocomposite by
      hydrothermal method. The characterization of Ag/HNT/MoS2 nanocomposite were
      investigated by field emission scanning electron microscopy (FE-SEM), Fourier
      transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM),
      X-ray photoelectron spectra (XPS), energy dispersive X-ray spectroscopy (EDS) and
      X-ray diffraction (XRD) analyses. The nanocomposite modified carbon paste
      electrode (CPE) was applied for the electrocatalytic detection of nitrite in
      aqueous solutions. It was demonstrated that the treatment of HNTs with Ag and
      MoS2 materials enhanced the catalytic performance of modified CPE. At optimal
      experimental conditions, the designed sensor displayed remarkable sensing ability
      toward nitrite oxidation, offering a good linearity from 2 to 425 uM. The limit
      of detection (LOD) of the proposed strategy was estimated to be 0.7 uM based S/N
      = 3. The good reproducibility, acceptable stability, fast response time and anti
      interference performance of the proposed assay suggests that the modified CPE has
      great potential working as a nitrite electrochemical sensor for environmental
      applications.

PMID- 29573729
TI  - Contrastive study for coadsorption of copper and two dihydroxybenzene isomers by
      a multi-amine modified resin.
AB  - Coadsorption of Cu(II) and two dihydroxybenzene isomers (hydroquinone, HQ and
      catechol, CAT) onto a multi-amine modified resin (CEAD) were comparatively
      studied. The presence of Cu(II) promoted adsorption of both HQ and CAT by a
      maximum of 25.8% and 41.6%, respectively. However, two diphenols exerted a very
      different influence on Cu(II) uptake. Higher concentrations of HQ consistently
      suppressed Cu(II) adsorption while the coexistence of CAT facilitated it,
      especially at lower CAT concentrations. The interactions among solutes and
      adsorbents were revealed by means of kinetic tracking, sequential adsorption
      experiments, and characterizations/calculations (FTIR, XPS, MINTEQ and DFT).
      Cu(II) and HQ/CAT competed for amine sites with the order of adsorption affinity
      as HQ > Cu(II) > CAT. The bridging effect of Cu(II) forming ternary complexes
      (amine-Cu-CAT/HQ) on the resin phase was the dominant mechanism for the enhanced
      adsorption of diphenols. The [Cu-CAT] complex species showed a lower affinity to
      bind directly to amine sites compared with free Cu2+. Instead, the complex could
      be attracted by the polyphenyl matrix of CEAD, contributing to the increase of
      Cu(II) adsorption. Additionally, Cu(II) and diphenols were successively
      recovered, and CEAD could be stably reused. The findings will guide adsorbent
      applications and the environmental fate of concurrent heavy metals and phenolic
      compounds.

PMID- 29573730
TI  - Mussel-inspired functionalization of electrochemically exfoliated graphene: Based
      on self-polymerization of dopamine and its suppression effect on the fire hazards
      and smoke toxicity of thermoplastic polyurethane.
AB  - The suppression effect of graphene in the fire hazards and smoke toxicity of
      polymer composites has been seriously limited by both mass production and weak
      interfacial interaction. Though the electrochemical preparation provides an
      available approach for mass production, exfoliated graphene could not strongly
      bond with polar polymer chains. Herein, mussel-inspired functionalization of
      electrochemically exfoliated graphene was successfully processed and added into
      polar thermoplastic polyurethane matrix (TPU). As confirmed by SEM patterns of
      fracture surface, functionalized graphene possessing abundant hydroxyl could
      constitute a forceful chains interaction with TPU. By the incorporation of 2.0 wt
      % f-GNS, peak heat release rate (pHRR), total heat release (THR), specific
      extinction area (SEA), as well as smoke produce rate (SPR) of TPU composites were
      approximately decreased by 59.4%, 27.1%, 31.9%, and 26.7%, respectively. A
      probable mechanism of fire retardant was hypothesized: well-dispersed f-GNS
      constituted tortuous path and hindered the exchange process of degradation
      product with barrier function. Large quantities of degradation product gathered
      round f-GNS and reacted with flame retardant to produce the cross-linked and high
      degree graphited residual char. The simple functionalization for
      electrochemically exfoliated graphene impels the application of graphene in the
      fields of flame retardant composites.

PMID- 29573728
TI  - Biofunctionalization of PAMAM-montmorillonite decorated poly (E-caprolactone)
      chitosan electrospun nanofibers for cell adhesion and electrochemical
      cytosensing.
AB  - The construction and biofunctionalization of the poly (E-caprolactone) (PCL)
      chitosan (CHIT) nanofibrous mats, which included Polyamidoamine (PAMAM) dendrimer
      modified montmorillonite (Mt), for the cell adhesion and electrochemical
      cytosensing were accomplished in this report. After the intercalation of the
      PAMAM generation zero dendrimer into the Mt, PAMAM-Mt decorated PCL-CHIT
      electrospun nanofibers were formed. The addition of PAMAM caused the decrease of
      contact angle of PCL-CHIT nanofibers. The covalent immobilization of a tripeptide
      namely Arginylglycylaspartate (RGD) on both the PCL-CHIT/Mt and PCL-CHIT/PAMAM-Mt
      surface was carried out. U87-MG and HaCaT (negative control) cell lines were
      incubated on the PCL-CHIT/Mt/RGD and PCL-CHIT/PAMAM-Mt/RGD. The proliferation
      studies and imaging of the cells were carried out on these fibers. Finally,
      electrochemical measurements were performed after each modification step by
      differential pulse/cyclic voltammetry and electrochemical impedance spectroscopy.
      U87-MG cells were grown better than HaCaT cells on the PCL-CHIT/PAMAM-Mt/RGD
      surfaces. To the best of our knowledge, there is no study that developed
      electrochemical cytosensor using electrospun nanofibers as a cell adhesion
      platform.

PMID- 29573731
TI  - Sulfate-reducing mixed communities with the ability to generate bioelectricity
      and degrade textile diazo dye in microbial fuel cells.
AB  - The biotreatment of recalcitrant wastes in microbial fuel cells (MFCs) rather
      than chemical, physical, and advanced oxidation processes is a low-cost and eco
      friendly process. In this study, sulfate-reducing mixed communities in MFC anodic
      chamber were employed for simultaneous electricity generation, dye degradation,
      and sulfate reduction. A power generation of 258 +/- 10 mW/m2 was achieved under
      stable operating conditions in the presence of electroactive sulfate-reducing
      bacteria (SRB). The SRBs dominant anodic chambers result in dye, chemical oxygen
      demand (COD), and sulfate removal of greater than 85% at an initial COD (as
      lactate)/SO42- mass ratio of 2.0 and dye concentration of 100 mg/L. The effects
      of the COD/SO42- ratio (5.0:1.0-0.5:1.0) and initial diazo dye concentration (100
      1000 mg/L) were studied to evaluate and optimize the MFC performance. Illumina
      Miseq technology for bacterial community analysis showed that Proteobacteria
      (89.4%), Deltaproteobacteria (52.7%), and Desulfovibrio (48.2%) were most
      dominant at phylum, class, and genus levels, respectively, at the MFC anode.
      Integration of anaerobic SRB culture in MFC bioanode for recalcitrant chemical
      removal and bioenergy generation may lead to feasible option than the currently
      used technologies in terms of overall pollutant treatment.

PMID- 29573732
TI  - Continuous erector spinae plane block for an open pyeloplasty in an infant.

PMID- 29573733
TI  - Electroencephalographic correlates of low-frequency vagus nerve stimulation
      therapy for Crohn's disease.
AB  - OBJECTIVES: In the context of the first clinical trial of vagus nerve stimulation
      (VNS) in Crohn's disease (CD), our main objective was to quantify the acute and
      chronic effects of VNS on brain activity in CD patients. METHODS: We measured the
      electroencephalogram (EEG) in 9CD patients under VNS at 10 Hz just before VNS
      initiation, after 6 weeks and after 12 months of chronic VNS. RESULTS: Acute VNS
      induced increased spectral power in delta and theta bands on frontal, temporal
      and occipital electrodes. The main significant modulation was the 12 months'
      chronic effect of VNS which consisted mainly in a decreased power in the alpha
      frequency band which was correlated with the normalization of bowel mucosal
      inflammation, anxiety state and vagal tone. CONCLUSIONS: In addition to the
      activation of vagal efferent fibers that regulate the autonomic nervous system,
      our data suggest that chronic VNS has a regulatory action via afferent vagal
      fibers on anxio-depressive symptomatology associated to CD, which could be
      directly highlighted by the modulation of EEG alpha power known to be associated
      to depressed states. SIGNIFICANCE: This is the first report of the central
      effects of VNS in CD patients.

PMID- 29573734
TI  - A systematic data acquisition and mining strategy for chemical profiling of Aster
      tataricus rhizoma (Ziwan) by UHPLC-Q-TOF-MS and the corresponding anti-depressive
      activity screening.
AB  - In this study, a systematic data acquisition and mining strategy aimed at the
      traditional Chinese medicine (TCM) complex system based on ultra high-performance
      liquid chromatography coupled with quadrupole time of flight mass spectrometry
      (UHPLC-Q-TOF-MS) was reported. The workflow of this strategy is as follows:
      First, the high resolution mass data are acquired by both data-dependent
      acquisition mode (DDA) and data-independent acquisition mode (DIA). Then a global
      data mining that combined targeted and non-targeted compound finding is applied
      to analyze mass spectral data. Furthermore, some assistant tools, such as key
      product ions (KPIs), are employed for compound hunting and identification. The
      TCM Ziwan (ZW, Aster tataricus rhizoma) was used to illustrate this strategy for
      the first time. In this research, total 131 compounds including organic acids,
      peptides, terpenes, steroids, flavonoids, coumarins, anthraquinones and aldehydes
      were identified or tentatively characterized in ZW based on accurate mass
      measurements within +/-5 ppm error, and 50 of them were unambiguously confirmed
      by comparing standard compounds. Afterwards, based on the traditional Chinese
      medical theory and the key determinants of firing patterns of ventral tegmental
      area (VTA) dopamine (DA) neurons in the development of depression, the confirmed
      compounds were subsequently evaluated the pharmacological effect of activity of
      VTA DA neurons and anti-depressive efficacy. This research provided not only a
      chemical profiling for further in vivo study of ZW, but also an efficient data
      acquisition and mining strategy to profile the chemical constituents and find new
      bioactive substances for other TCM complex system.

PMID- 29573735
TI  - Development and validation of a rapid LC-MS/MS method for simultaneous
      quantification of arecoline and its two active metabolites in rat plasma and its
      application to a pharmacokinetic study.
AB  - Arecoline is the primary active and toxic constituent of areca nut. Arecaidine
      and arecoline N-oxide are two major active metabolites of arecoline. In this
      work, an accurate and simple high performance liquid chromatography tandem mass
      spectrometry method for simultaneous quantification of arecoline, arecaidine and
      arecoline N-oxide in rat plasma was developed and fully validated to study their
      pharmacokinetic behaviors in rats. After extracted from rat plasma by protein
      precipitation with methanol and then concentrated, the analytes were
      chromatographic separated on a Sepax Sapphire C18 analytical column. The mobile
      phase consisted of methanol and 2 mM ammonium acetate buffer solution containing
      0.2% (v/v) formic acid (8:92, v/v) under isocratic elution. The analytes were
      detected by multiple reaction monitoring (MRM) with an electrospray ionization
      source in the positive ion mode. The transitions of m/z 156.2 -> 53.2, m/z 142.2 
      > 44.2 and m/z 172.2 -> 60.2 were selected for arecoline, arecaidine and
      arecoline N-oxide, respectively. The method was linear over the concentration
      range of 0.5-100 ng/mL for arecoline, 5-5000 ng/mL for arecaidine and arecoline N
      oxide with no carry-over effect. The accuracies and intra- and inter-batch
      precisions were all within the acceptance limits. No matrix effect and potential
      interconversion between the analytes and other metabolites were observed in this
      method. The validated method was further employed to a preclinical
      pharmacokinetic study of arecoline, arecaidine and arecoline N-oxide after oral
      treatment with 20 mg/kg arecoline to rats.

PMID- 29573736
TI  - High throughput method to characterize acid-base properties of insoluble drug
      candidates in water.
AB  - In drug design experimental characterization of acidic groups in candidate
      molecules is one of the more important steps prior to the in-vivo studies.
      Potentiometry combined with Yasuda-Shedlovsky extrapolation is one of the more
      important strategy to study drug candidates with low solubility in water,
      although, it requires a large number of sequences to determine pKa values at
      different solvent-mixture compositions to, finally, obtain the pKa in water
      (pwwKa) by extrapolation. We have recently proposed a method which requires only
      two sequences of additions to study the effect of organic solvent content in
      liquid chromatography mobile phases on the acidity of the buffer compounds
      usually dissolved in it along wide ranges of compositions. In this work we
      propose to apply this method to study thermodynamic pwwKa of drug candidates with
      low solubilities in pure water. Using methanol/water solvent mixtures we study
      six pharmaceutical drugs at 25  degrees C. Four of them: ibuprofen, salicylic
      acid, atenolol and labetalol, were chosen as members of carboxylic, amine and
      phenol families, respectively. Since these compounds have known pwwKa values,
      they were used to validate the procedure, the accuracy of Yasuda-Shedlovsky and
      other empirical models to fit the behaviors, and to obtain pwwKa by
      extrapolation. Finally, the method is applied to determine unknown thermodynamic
      pwwKa values of two pharmaceutical drugs: atorvastatin calcium and the two
      dissociation constants of ethambutol. The procedure proved to be simple, very
      fast and accurate in all of the studied cases.

PMID- 29573737
TI  - Polymerization shrinkage stress of resin-based dental materials: A systematic
      review and meta-analyses of technique protocol and photo-activation strategies.
AB  - PURPOSE: A systematic review was conducted to determine whether there were any
      alternative technique or additional step strategies available to reduce and
      control polymerization shrinkage stress development in dental resin-based
      restorative materials. DATA SOURCES: This report followed the PRISMA Statement. A
      total of 36 studies were included in this review. Two reviewers performed a
      literature search up to December 2016, without restriction of the year of
      publication, in seven databases: PubMed, Web of Science, Scopus, SciELO, LILACS,
      IBECS, and BBO. STUDY SELECTION: Only in vitro studies that evaluated
      polymerization shrinkage stress by direct testing were included. Pilot studies,
      reviews and in vitro studies that evaluated polymerization shrinkage stress by
      indirect methods (e.g., microleakage or cuspal deflection measurements), finite
      elemental analysis or mathematical models were excluded. Of the 6.113 eligible
      articles, 36 studies were included in the qualitative analysis, and the meta
      analysis was performed with 25 studies. A global comparison was performed with
      random-effects models (alpha = 0.05). The strategies were subdivided as follows:
      the use of an alternative technique protocol of placing the material inside the
      tooth cavity; the modification of the irradiation intensity or total energy
      delivered to the material; the use of an alternative light-curing source; or the
      use of an alternative photo-activation mode. All alternative strategies showed
      statistically significant differences when compared with their respective
      controls (p < 0.05). CONCLUSION: The use of alternative light-curing sources
      contributed more to minimizing stress development than placing the material by
      means of an alternative technique protocol or by modifying the irradiant
      intensity or total energy delivered to the material during photo-activation.
      Moreover, the use of an alternative photo-activation mode (intermittent light,
      exponential, soft-start or pulse delay modes) was shown to be an effective
      strategy for reducing and controlling stress development in resin-based dental
      materials.

PMID- 29573738
TI  - Mind maps and network analysis to evaluate conceptualization of complex issues: A
      case example evaluating systems science workshops for childhood obesity
      prevention.
AB  - Across disciplines, it is common practice to bring together groups to solve
      complex problems. Facilitators are often asked to help groups organize
      information about and better understand the problem in order to develop and
      prioritize solutions. However, despite existence of several methods to elicit and
      characterize how individuals and groups think about and conceptualize an issue,
      many are difficult to implement in practice-based settings where resources such
      as technology and participant time are limited and research questions shift over
      time. This paper describes an easy-to-implement diagramming technique for
      eliciting conceptualization and a flexible network analysis method for
      characterizing changes in both individual and group conceptualization. We use a
      case example to illustrate how we used the methods to evaluate African American
      adolescent's conceptual understanding of obesity before and after participating
      in a series of four systems thinking workshops. The methods produced results that
      were sensitive to changes in conceptualization that were likely driven by the
      specific activities employed during the workshop sessions. The methods appear
      strong for capturing salient levels of conceptualization at both individual and
      collective levels. The paper concludes with a critical examination of strengths
      and weaknesses of the methods and implications for future practice and research.

PMID- 29573739
TI  - Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence
      score in ER-positive/HER2-negative breast cancer.
AB  - BACKGROUND: Recent studies have shown that tumors with extensive tumor
      infiltrating lymphocytes (TILs) have a higher probability of pathologic complete
      response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast
      cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen
      receptor (ER)-positive/HER2-negative breast cancer. METHODS: We evaluated the
      percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS
      was obtained by examining slides of surgical specimens by standardized
      methodology proposed by the international TIL Working Group. TIL levels were
      categorized as high (>= 60%), intermediate (11-59%), or low (<= 10%). All tumors
      were treatment-naive. RESULTS: Ninety-seven (49.0%), 88 (44.4%), and 13 patients
      (6.6%) had low, intermediate, and high TIL levels, respectively. There was a
      significant but weak correlation between continuous RS and continuous TIL levels
      (Pearson's R = 0.201, p = 0.004). The mean RS was significantly highest in high
      TIL tumors (17.8 +/- 10.7 in low TIL tumors, 19.4 +/- 8.7 in intermediate TIL
      tumors, and 26.2 +/- 8.2 in high TIL tumors; p = 0.014). However, when we
      compared categorized RS and TIL levels, we found that tumors with high TIL levels
      tended to have higher RS (>= 26) but it was not significant (p = 0.155).
      Furthermore, multivariate analysis revealed that high RS was not an independent
      factor associated with high TIL levels. Chemo-endocrine therapy was more
      frequently performed among patients with high TILs and less frequently among
      those with low or intermediate TILs (p <  0.001). CONCLUSIONS: Despite of a weak
      correlation between continuous TIL levels and RS, we found that tumors with high
      TIL levels tended to have a higher RS in ER-positive/HER2-negative breast cancer.
      Further study is warranted considering the clinical outcomes.

PMID- 29573740
TI  - Posturography and dynamic pedobarography in lame dogs with elbow dysplasia and
      cranial cruciate ligament rupture.
AB  - BACKGROUND: The usefulness of studying posture and its modifications due to
      locomotor deficiencies of multiple origins has been widely proven in humans. To
      assess its suitability in the canine species, static posturography and dynamic
      pedobarography were performed on lame dogs affected with unilateral elbow
      dysplasia and cranial cruciate ligament rupture by using a pressure platform.
      With this objective, statokinesiograms and stabilograms, the percentage of
      pressure distribution between limbs, paw area, mean pressure, and peak pressure,
      were obtained from lame and sound dogs. These data were compared with Peak
      Vertical Force values originated from a force platform in the same recording
      sessions. RESULTS: Significant differences were found in the parameters mentioned
      above between sound and lame dogs and limbs. CONCLUSIONS: Posturography and
      pedobarography are useful and reliable for the monitoring of fore and hindlimb
      lameness in dogs, providing a new set of parameters for lameness detection.

PMID- 29573741
TI  - HIV-1 Tat-induced diarrhea is improved by the PPARalpha agonist,
      palmitoylethanolamide, by suppressing the activation of enteric glia.
AB  - BACKGROUND: Diarrhea is a severe complication in HIV-1-infected patients with
      Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major
      underlying cause. Beside its direct enterotoxic effects, Tat protein has been
      recently shown to affect enteric glial cell (EGC) activity. EGCs regulate
      intestinal inflammatory responses by secreting pro-inflammatory molecules;
      nonetheless, they might also release immune-regulatory factors, as
      palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating
      PPARalpha receptors. We aimed at clarifying whether EGCs are involved in HIV-1
      Tat-induced diarrhea and if PEA exerts antidiarrheal activity. METHODS: Diarrhea
      was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1.
      PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR)
      antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF
      kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B
      and NO levels were measured in EGC submucosal plexi lysates, respectively. To
      verify whether PEA effects were PPARalpha-mediated, PPARalpha-/- mice were also
      used. After 7 days from diarrhea induction, endogenous PEA levels were measured
      in submucosal plexi homogenates deriving from rats and PPARalpha-/- mice.
      RESULTS: HIV-1 Tat protein induced rapid onset diarrhea alongside with a
      significant activation of EGCs. Tat administration significantly increased all
      hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and
      S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1
      Tat exposure in both wildtype and knockout animals. In PPARalpha-/- mice, PEA
      displayed no effects. In wildtype rats, PEA, via PPARalpha-dependent mechanism,
      resulted in a significant antidiarrheal activity in parallel with marked
      reduction of EGC-sustained neuroinflammation. CONCLUSIONS: EGCs mediate HIV-1 Tat
      induced diarrhea by sustaining the intestinal neuroinflammatory response. These
      effects are regulated by PEA through a selective PPARalpha-dependent mechanism.
      PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea.

PMID- 29573742
TI  - Systemic inflammation in dogs with advanced-stage heart failure.
AB  - BACKGROUND: Although human studies have shown that inflammation plays a role in
      the development of congestive heart failure, scarce information exists on white
      blood cell count (WBC) and differential cell counts in various stages of heart
      failure in man and dogs. A few studies demonstrated increased concentrations of C
      reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs.
      Our research aimed to investigate whether CRP concentration, WBC and neutrophil
      count (NEUT), as markers of systemic inflammation, are elevated in canine
      cardiovascular patients. We also aimed to find out whether there is an
      association between CRP concentration and WBC and NEUT, as well as associations
      between these inflammatory markers and selected echocardiographic parameters.
      Sixty-two client-owned canine cardiac patients and 12 healthy dogs were included
      in the study. The patients were classified into International Small Animal
      Cardiac Health Council classes (ISACHC I-III). The serum CRP concentration was
      determined using a canine CRP test kit. WBC and NEUT were determined using an
      automated hematology analyzer. RESULTS: Significantly higher serum CRP
      concentration, WBC and NEUT were found in the decompensated stage of heart
      failure (ISACHC III) compared with healthy dogs and with patients in ISACHC group
      II and ISACHC group I. Serum CRP concentration significantly positively
      correlated with WBC (r = 0.65, P < 0.001) and NEUT (r = 0.58, P = 0.002) in the
      ISACHC III group, while no significant correlations were found in the ISACHC I
      and II groups. A significant negative correlation between serum CRP concentration
      and the left ventricular ejection fraction (r = - 0.49, P = 0.046) and a
      significant positive correlation between CRP and the E wave velocity of the
      mitral valve inflow (r = 0.52, P = 0.046) were found in the ISACHC III group.
      CONCLUSIONS: The CRP concentration, WBC and NEUT were significantly increased in
      advanced-stage heart failure patients in comparison with compensated patients and
      healthy dogs, which indicate the presence of systemic inflammation. However,
      normal CRP concentration and normal WBC and NEUT can also be present in heart
      failure.

PMID- 29573743
TI  - Seroprevalence of Brucella suis in eastern Latvian wild boars (Sus scrofa).
AB  - Brucellosis due to Brucella suis biovar 2 is one of the most important endemic
      diseases in wild boar (Sus scrofa) populations in Europe. The aim of the present
      study was to determine the seroprevalence of brucellosis in wild boars in the
      eastern part of Latvia. Wild boars killed by hunters in the period from January
      to April 2015 (n = 877) and from March to April in 2016 (n = 167) were examined
      for antibodies against B. suis by the Rose Bengal test (RBT), a complement
      fixation test (CFT), and by enzyme-linked immunosorbent assays. In 2015, 199
      samples (22.7%) were positive by RBT and/or CFT while 36 samples (21.6%) were
      seropositive in 2016. Of the Brucella seropositive samples from 2015 and 2016 (n
      = 235), 162 (68.9%) were also seropositive to Yersinia enterocolitica.
      Considering cross-reactivity of serological tests, the seroprevalence of B. suis
      biovar 2 exposure in wild boars in the eastern part of Latvia was calculated to
      14.0% in 2015 and 9.6% in 2016. From selected seropositive samples (42 in 2015
      and 36 in 2016) total DNA was extracted and analyzed with an IS711-based nested
      polymerase chain reaction (PCR) assay. Species and biovar identification was
      conducted for bacteria isolated in monoculture from PCR positive samples by
      species specific primers and Bruce-ladder multiplex PCR. Brucella suis biovar 2
      was isolated from 12/20 samples in 2015 and 9/9 samples in 2016. The average
      seroprevalence was relatively low compared to that found in certain other
      European countries. Males and females had an equal level of seropositivity, but a
      positive age-trend was observed for both males and females.

PMID- 29573744
TI  - Optimization of treatment planning workflow and tumor coverage during daily
      adaptive magnetic resonance image guided radiation therapy (MR-IGRT) of
      pancreatic cancer.
AB  - BACKGROUND: To simplify the adaptive treatment planning workflow while achieving
      the optimal tumor-dose coverage in pancreatic cancer patients undergoing daily
      adaptive magnetic resonance image guided radiation therapy (MR-IGRT). METHODS: In
      daily adaptive MR-IGRT, the plan objective function constructed during simulation
      is used for plan re-optimization throughout the course of treatment. In this
      study, we have constructed the initial objective functions using two methods for
      16 pancreatic cancer patients treated with the ViewRayTM MR-IGRT system: 1) the
      conventional method that handles the stomach, duodenum, small bowel, and large
      bowel as separate organs at risk (OARs) and 2) the OAR grouping method. Using OAR
      grouping, a combined OAR structure that encompasses the portions of these four
      primary OARs within 3 cm of the planning target volume (PTV) is created. OAR
      grouping simulation plans were optimized such that the target coverage was
      comparable to the clinical simulation plan constructed in the conventional
      manner. In both cases, the initial objective function was then applied to each
      successive treatment fraction and the plan was re-optimized based on the
      patient's daily anatomy. OAR grouping plans were compared to conventional plans
      at each fraction in terms of coverage of the PTV and the optimized PTV (PTV OPT),
      which is the result of the subtraction of overlapping OAR volumes with an
      additional margin from the PTV. RESULTS: Plan performance was enhanced across a
      majority of fractions using OAR grouping. The percentage of the volume of the PTV
      covered by 95% of the prescribed dose (D95) was improved by an average of 3.87 +/
      4.29% while D95 coverage of the PTV OPT increased by 3.98 +/- 4.97%. Finally,
      D100 coverage of the PTV demonstrated an average increase of 6.47 +/- 7.16% and a
      maximum improvement of 20.19%. CONCLUSIONS: In this study, our proposed OAR
      grouping plans generally outperformed conventional plans, especially when the
      conventional simulation plan favored or disregarded an OAR through the assignment
      of distinct weighting parameters relative to the other critical structures. OAR
      grouping simplifies the MR-IGRT adaptive treatment planning workflow at
      simulation while demonstrating improved coverage compared to delivered pancreatic
      cancer treatment plans in daily adaptive radiation therapy.

PMID- 29573746
TI  - Effects of inter-twin vascular anastomoses of monochorionic twins with selective
      intrauterine growth restriction on the contents of placental mitochondria DNA.
AB  - BACKGROUND: Placental mitochondrial DNA (mtDNA) has been proposed to be an
      indicator for placental hypoxia. This study was designed to evaluate the effect
      of vascular anastomoses between monochorionic (MC) twins on placental mtDNA.
      METHODS: In this study, twin-twin transfusion syndrome (TTTS) treated with laser
      therapy and MC twins without TTTS (without laser therapy) resulting in two live
      babies were included in this study. The placental mtDNA fold changes (FC) between
      the small and large twins were analyzed using real-time quantitative PCR. TTTS
      twins with selective intrauterine growth restriction (sIUGR) are categorized as
      group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as
      group 3, and MC twins without both TTTS and sIUGR as group 4. RESULTS: There were
      seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases.
      The placental mtDNA FC were significantly higher in group 1 (1.57 +/- 0.9)
      compared to that of the group 3 (0.86 +/- 0.6). CONCLUSION: In MC twin
      pregnancies with sIUGR, the placental mtDNA FC between the small and large twins
      are different between cases with and without inter-twin anastomoses. These
      findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may
      provide rescue perfusion from the appropriate-for-gestational-age twin to the
      sIUGR one.

PMID- 29573745
TI  - Monocular enucleation alters retinal waves in the surviving eye.
AB  - BACKGROUND: Activity in neurons drives afferent competition that is critical for
      the refinement of nascent neural circuits. In ferrets, when an eye is lost in
      early development, surviving retinogeniculate afferents from the spared eye
      spread across the thalamus in a manner that is dependent on spontaneous retinal
      activity. However, how this spontaneous activity, also known as retinal waves,
      might dynamically regulate afferent terminal targeting remains unknown. METHODS:
      We recorded retinal waves from retinae ex vivo using multi-electrode arrays.
      Retinae came from ferrets who were binocular or who had one eye surgically
      removed at birth. Linear mixed effects models were used to investigate the
      effects of early monocular enucleation on retinal wave activity. RESULTS: When an
      eye is removed at birth, spontaneous bursts of action potentials by retinal
      ganglion cells (RGCs) in the surviving eye are shorter in duration. The
      shortening of RGC burst duration results in decreased pairwise RGC correlations
      across the retina and is associated with the retinal wave-dependent spread of
      retinogeniculate afferents previously reported in enucleates. CONCLUSION: Our
      findings show that removal of the competing eye modulates retinal waves and could
      underlie the dynamic regulation of competition-based refinement during
      retinogeniculate development.

PMID- 29573747
TI  - Implementing the Baby One Program: a qualitative evaluation of family-centred
      child health promotion in remote Australian Aboriginal communities.
AB  - BACKGROUND: A healthy start predicts better health in later life. Many remote
      living Aboriginal and Torres Strait Islander Australian families lack access to
      consistent, culturally-safe health services. This paper presents a study of
      implementation of the Baby One Program (BOP). The BOP was designed as a family
      centred, Indigenous Healthworker-led, home-visiting model of care focused on
      promoting family health to give children the best start to life. It was developed
      by Aboriginal community-controlled Apunipima Cape York Health Council and
      delivered in Queensland Cape York remote communities. We aimed to determine how
      the BOP was implemented, enablers, strategies used and formative implementation
      outcomes. METHODS: The qualitative approach utilised theoretical and purposive
      sampling to explore people's experiences of a program implementation process.
      Data were generated from semi-structured interviews with four family members
      enrolled in the BOP and 24 Apunipima staff members. In addition, twenty community
      members, including two program users, participated in a men's community focus
      group. The findings are presented according to themes arising from the data.
      RESULTS: The BOP was rolled out in nine remote Cape York communities between July
      2014 and December 2015 and there was high uptake. Indigenous Healthworkers were
      supported by midwives and maternal and child health nurses to deliver health
      education to 161 eligible families. The key to effective implementation of family
      centred care appeared to be the relationships formed between health
      practitioners, especially Indigenous Healthworkers, and families. The data
      revealed the following themes: challenging environments for new families and
      valuing cultural ways, resourcing program delivery, working towards a team
      approach, negotiating the cultural interface, engaging families, exchanging
      knowledge through 'yarning', strengthening the workforce, and seeing health
      changes in families. Healthworker education and training, and knowledge exchange
      between Healthworkers, midwives and nurses was critical to program effectiveness.
      The program continues to grow despite substantial logistic, financial and
      practical challenges. CONCLUSIONS: This study describes an evolving process and
      explores how health providers connect with families and how the program responds
      to family and cultural issues. Program development is ongoing; strengthened by
      more community-level involvement, embedded strategies for ongoing self-evaluation
      and continuous quality improvements that are responsive to family needs.

PMID- 29573748
TI  - High serum levels of caspase-cleaved cytokeratin-18 are associated with malignant
      middle cerebral artery infarction patient mortality.
AB  - BACKGROUND: There have been found apoptotic changes in brain tissue samples from
      humans after cerebral ischemia. Caspase-cleaved cytokeratin (CCCK)-18 could
      appears in blood during apoptosis. High circulating levels of CCCK-18 have been
      associated with a poor prognosis in patients with cerebral process, such as
      traumatic brain injury and spontaneous cerebral hemorrhage. However, they have
      not been explored in patients with ischemic stroke. Thus, the aim of this study
      was to determine whether there is an association between serum CCCK-18 levels and
      mortality in patients with severe malignant middle cerebral artery infarction
      (MMCAI). METHODS: This was an observational, prospective and multicentre study.
      We included patients with severe MMCAI. We considered MMCAI as severe when
      Glasgow Coma Scale (GCS) was lower than 9. We measured serum CCCK-18 levels at
      the diagnosis moment of the severe MMCAI. RESULTS: We found that non-surviving
      severe MMCAI patients (n = 33) showed lower GCS and platelet count, and higher
      serum CCCK-18 levels than survivor ones (n = 33). We found an area under the
      curve (AUC) of serum CCCK-18 levels to predict 30-day mortality of 82% (95% CI =
      71%-91%; p < 0.001). In the multiple logistic regression analysis was found that
      serum CCCK-18 levels were associated with 30-day mortality (OR = 1.023; 95% CI =
      1.010-1.037; p = 0.001) after to control for platelet count and GCS. CONCLUSIONS:
      To our knowledge, this is the first series reporting data on serum CCCK-18 levels
      in ischemic stroke patients. The novel findings of our study were that non
      surviving severe MMCAI patients had higher serum CCCK-18 levels than surviving
      patients, and that there is an association between high serum CCCK-18 levels and
      MMCAI patients mortality.

PMID- 29573749
TI  - Central blockade of NLRP3 reduces blood pressure via regulating inflammation
      microenvironment and neurohormonal excitation in salt-induced prehypertensive
      rats.
AB  - BACKGROUND: Inflammation has been implicated in the development of cardiovascular
      disease. We determined whether nod-like receptor with pyrin domain containing 3
      (NLRP3) involved in the process of prehypertension, central blockade of NLRP3
      decreased inflammation reaction, regulated neurohormonal excitation, and delayed
      the progression of prehypertension. METHODS: Prehypertensive rats were induced by
      8% salt diet. The rats on high-salt diet for 1 month were administered a specific
      NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks.
      ELISA, western blotting, immunohistochemistry, and flow cytometry were used to
      measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine
      ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion
      molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection,
      respectively. RESULTS: NLRP3 expression in PVN was increased significantly in
      prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T
      cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1
      significantly increased. The balance between 67-kDa isoform of glutamate
      decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma
      norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric
      acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure,
      reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters.
      Blood pressure and inflammatory markers were upregulated after termination of
      central blockage NLRP3. CONCLUSIONS: Salt-induced prehypertension is partly due
      to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive
      response, possibly via downregulating the cascade reaction triggered by
      inflammation and restoring the balance of neurotransmitters.

PMID- 29573750
TI  - Genome-wide association of changes in swine feeding behaviour due to heat stress.
AB  - BACKGROUND: Heat stress has a negative impact on pork production, particularly
      during the grow-finish phase. As temperature increases, feeding behaviour changes
      in order for pigs to decrease heat production. The objective of this study was to
      identify genetic markers associated with changes in feeding behaviour due to heat
      stress. Feeding data were collected on 1154 grow-finish pigs using an electronic
      feeding system from July 2011 to March 2016. In this study, days were classified
      based on the maximum temperature humidity index (THI) during the day as "Normal"
      (< 23.33  degrees C), "Alert" (23.33  degrees C <= * < 26.11  degrees C),
      "Danger" (26.11  degrees C <= * < 28.88  degrees C), and "Emergency" (>= 28.88 
      degrees C). Six hundred and eighty-one pigs that experienced more than one THI
      category were genotyped using a variety of SNP platforms, with final genotypes
      imputed to approximately 60,000 markers. RESULTS: A genome-wide association study
      (GWAS) for change in feeding behaviour between each pair of THI categories (six
      pairs) was conducted. Estimates of heritability for differences in feeding
      activity between each of the THI categories were low (0.02 +/- 0.03) to moderate
      (0.21 +/- 0.04). Sixty-six associations which explained more than 1% of the
      genomic variation for a trait were detected across the six GWAS, with the
      smallest number of associations detected in comparisons with Emergency THI. Gene
      ontology enrichment analysis showed that biological processes related to immune
      response and function were over-represented among the genes located in these
      regions. CONCLUSIONS: Genetic differences exist for changes in feeding behaviour
      induced by elevated ambient temperatures in grow-finish pigs. Selection for heat
      tolerant grow-finish pigs should improve production efficiency during warm months
      in commercial production. Genetic variation in heat shock, stress response and
      immune function genes may be responsible for the observed differences in
      performance during heat stress events.

PMID- 29573751
TI  - A hydatic cyst of the appendix mimicking a uterine lateral mass: a case report.
AB  - BACKGROUND: Hydatic cyst is a zoonotic disease caused by Echinococcus granulosus.
      It is a public health problem in Tunisia and remains endemic. It occurs in intra
      abdominal organs in 10-15% of the cases, particularly in the liver representing
      the most common affected organ. The aim of the case is to highlight the scarcity
      of this appendicle origin and to consider it among the differential diagnosis of
      any intra-abdominal cystic lesion. CASE PRESENTATION: A 45-year-old Tunisian
      woman, with no past medical history, was admitted for a pelvic cystic mass. The
      clinical manifestation as well as the imaging findings were toward a lateral
      uterine mass. Our patient underwent appendectomy and resection of the mass. The
      patient had no recurrence at 2 years of follow-up. CONCLUSIONS: An extrahepatic
      hydatid cyst should be recognized among the differential diagnosis of any intra
      abdominal cystic lesion. Treatment should be based on surgical excision. Due to
      the risk of recurrence, a close follow-up is mandatory.

PMID- 29573752
TI  - Cochrane Review Summary: Support for healthy breastfeeding mothers with healthy
      term babies.

PMID- 29573753
TI  - Therapeutic Lies in Dementia Care: Should Psychologists Teach Others to be Person
      Centred Liars?
AB  - BACKGROUND: Therapeutic lies are frequently used communication strategies, often
      employed when the person with dementia does not share the same reality as the
      carer (James and Jackman, 2017; Tuckett 2004; Blum, 1994). Their use is complex
      and controversial, and a number of protocols have been produced to guide their
      usage (Mental Health Foundation, 2016). AIMS: The study examined clinicians'
      perspective on using therapeutic lies in their daily practice and their roles in
      encouraging the proper use of such a communication strategy. METHOD: This project
      sampled the views of clinicians, mainly psychologists, before and after attending
      a workshop on communication in dementia care; they were asked whether
      psychologists should have a role in teaching others to lie more effectively.
      RESULTS: It was found that following a comprehensive discussion on the use of
      lies, the clinicians recognized they lied more than they had originally thought,
      and were also significantly more supportive of having a role in teaching others
      to lie effectively. CONCLUSIONS: Clinicians, mainly psychologists, increased
      their support in the use of therapeutic lying. They considered others would
      benefit from the psychologists giving supervision in how to lie effectively.

PMID- 29573754
TI  - Beyond the limits - ECPR in putative fatal circumstances.
AB  - The eligibility criteria for applying extracorporeal cardiopulmonary
      resuscitation (ECPR) in patients with cardiac arrest are currently unclear. For
      those patients with hypothermic cardiac arrest, the European Resuscitation
      Council (ERC) Guidelines recommend considering ECPR only for patients with
      potassium <8 mmol/L and a body temperature below 32 degrees C, whereas the
      American Heart Association Guidelines (AHA) do not express this in a specific
      manner.We report the case of an urban unwitnessed out-of-hospital cardiac arrest
      patient found with her head immersed in water at a temperature of 23 degrees C.
      The patient presented an unclear history and a dire combination of clinical and
      laboratory parameters (asystole, arterial blood gas: pH 6.8, potassium 8.3
      mmol/L, lactate 16.0 mmol/L). Despite these poor prognostic indicators, ECPR was
      initiated after 95 minutes of CPR and the patient survived with a good
      neurological outcome.This case highlights the uncertainty in ECPR eligibility and
      prognostication, especially in those with hypothermia and water immersion for
      whom aggressive therapies may be warranted. Further data and improved strategies
      are required to delineate candidacy for this resource-intensive procedure better.

PMID- 29573755
TI  - Psychometric Properties of the Spanish Version of the Panic Disorder Severity
      Scale.
AB  - The Panic Disorder Severity Scale (PDSS) is a well-established measure of panic
      symptoms but few data exist on this instrument in non north-American samples. Our
      main goal was to assess the psychometric properties (internal consistency, test
      re-test reliability, inter-rater reliability, convergent and divergent validity)
      and the factor structure of the Spanish version. Ninety-four patients with a main
      diagnosis of panic disorder were assessed with the Spanish version of PDSS, the
      Anxiety Sensitivity Index-3 (ASI-3), the Panic and Agoraphobia Scale (PAS), the
      Beck Anxiety Inventory (BAI), the Beck Depression Inventory-II (BDI-II) the PDSS
      self-rating form and the Clinical Global Impression-Severity scale (CGI). The
      Spanish PDSS showed acceptable internal consistency (alpha = .74), excellent test
      retest (total score and items 1-6: alpha > .58, p .90) and medium to large
      convergent validity (r = .68, 95% CI [.54, .79], p < .01; r = .80, 95% CI [.70,
      .87], p < .01; r = .48, 95% CI [.28, .67], p < .01; BAI, PAS and ASI-3 total
      scores respectively). Data on divergent validity (BDI-II total score: r = .52,
      95% CI [.34, .67], p < .01) suggest some need for refinement of the PDSS. The
      confirmatory factor analysis suggested a two-factor modified model for the scale
      (nested chi2 = 14.01, df = 12, p < .001). The Spanish PDSS has similar
      psychometric properties as the previous versions and is a useful instrument to
      assess panic symptoms in clinical settings in Spanish-speaking populations.

PMID- 29573756
TI  - The effect of docking length on the risk of tail biting, tail-directed behaviour,
      aggression and activity level of growing pigs kept under commercial conditions.
AB  - Tail biting in domestic pigs relates to a range of risk factors, primarily in the
      pigs' environment. Preventive tail docking is widely used, and various
      experimental approaches suggest that docking reduces the risk of tail biting.
      However, whether the docking length affects the prevalence of tail biting
      outbreaks is less studied, as is how a shortened tail will affect pigs' social
      behaviour. The aim of this study was to investigate how three different tail
      docking lengths, measured at docking, as well as retained intact tails (Short:
      2.9 cm; Medium: 5.7 cm; Long: 7.5 cm; and Undocked) affected tail biting risk and
      behaviour directed at other finisher pigs with the same docking length treatment.
      Tail lesions were scored weekly, as was behaviour at pen level after introduction
      to finisher pens and until a potential outbreak of tail biting or slaughter. Pigs
      from four commercial herds (258 litters) entered the study. Before the pigs
      entered the finisher section and data collection started, some pigs were
      excluded, mainly due to tail biting outbreaks in the weaner section. The risk of
      a tail biting outbreak differed significantly between treatments (P=0.001), with
      a lowered risk of a tail biting outbreak in Short pens compared with Undocked
      (P<0.001) and Medium (P<0.05), and was affected by herd as well (P<0.001). Pens
      in the Long and Undocked treatments were pooled for the behavioural analysis due
      to low representation, especially in the Undocked treatment. The probability of
      tail contacts, where a pig interacted with a pen mate's tail, differed between
      docking length treatments and was highest in the Long/Undocked compared with the
      Short treatment (P<0.01), but docking length did not affect aggressive behaviour.
      Docking length affected the risk of a tail biting outbreak and the frequency of
      tail-directed behaviour in our participating herds, of which three reported a
      high prevalence of tail biting problems. Only the shortest docking length
      treatment (Short) reduced the tail biting risk, but did not completely prevent
      tail biting outbreaks.

PMID- 29573757
TI  - The Metacognitive Anger Processing (MAP) Scale - Validation in a Mixed Clinical
      and a Forensic In-Patient Sample.
AB  - BACKGROUND: The metacognitive approach by Wells and colleagues has gained
      empirical support with a broad range of symptoms. The Metacognitive Anger
      Processing (MAP) scale was developed to provide a metacognitive measure on anger
      (Moeller, 2016). In the preliminary validation, three components were identified
      (positive beliefs, negative beliefs and rumination) to be positively correlated
      with the anger. AIMS: To validate the MAP in a sample of mixed clinical patients
      (n = 88) and a sample of male forensic patients (n = 54). METHOD: The MAP was
      administered together with measures of metacognition, anger, rumination, anxiety
      and depressive symptoms. RESULTS: The MAP showed acceptable scalability and
      excellent reliability. Convergent validity was evidenced using the general
      metacognitive measure (MCQ-30), and concurrent validity was supported using two
      different anger measures (STAXI-2 and NAS). CONCLUSIONS: The MAP has promising
      potential to assess anger regulation problems by providing a framework on angry
      rumination as well as the belief structures that proposedly drive the selection
      of this maladaptive processing strategy as suggested in the metacognitive model.
      These findings may have implications for clinical interventions. For example,
      conducting functional analyses on anger rumination could increase the
      understanding of dysregulated anger processing and lead to new interventions
      focused on shifting thinking style.

PMID- 29573758
TI  - Age-related and photoperiodic variation of the DAZ gene family in the testis of
      the Syrian hamster (Mesocricetus auratus).
AB  - SummaryThe Deleted in AZoospermia (DAZ) gene family regulates the development,
      maturation and maintenance of germ cells and spermatogenesis in mammals. The DAZ
      family consists of two autosomal genes, Boule and Dazl (Daz-like), and the Daz
      gene on chromosome Y. The aim of this study was to analyze the localization of
      DAZL and BOULE during testicular ontogeny of the seasonal-breeding Syrian
      hamster, Mesocricetus auratus. We also evaluated the testicular expression of DAZ
      family genes under short- or long-photoperiod conditions. In the pre-pubertal and
      adult testis, DAZL protein was found mainly in spermatogonia. BOULE was found in
      the spermatogonia from 20 days of age and during the pre-pubertal and adult
      period it was also detected in spermatocytes and round spermatids. DAZL and BOULE
      expression in spermatogonia was strictly nuclear only in 20-day-old hamsters. We
      also detected the novel mRNA and protein expression of BOULE in Leydig cells. In
      adult hamsters, Dazl expression was increased in regressed testis compared with
      non-regressed testis and DAZL protein expression was restricted to primary
      spermatocytes in regressed testis. These results show that DAZL and BOULE are
      expressed in spermatogonia at early stages in the Syrian hamster, then both
      proteins translocate to the cytoplasm when meiosis starts. In the adult regressed
      testis, the absence of DAZL in spermatogonia might be related to the decrease in
      germ cell number, suggesting that DAZ gene family expression is involved in
      changes in seminiferous epithelium during photoregression.

PMID- 29573759
TI  - Executive Dysfunction and Depression in Pediatric Temporal Lobe Epilepsy: The
      Contribution of Hippocampal Sclerosis and Psychosocial Factors.
AB  - OBJECTIVES: Temporal lobe epilepsy (TLE) has been identified as a risk factor for
      increased depression features in children and adolescents; however, less is known
      regarding specific neurocognitive predictors of depression in this population
      above and beyond seizure-specific and sociodemographic factors. METHODS: The
      study included 62 patients with TLE (64% male) aged 8 to 16 years (M=12.62;
      SD=2.26) who underwent comprehensive neuropsychological evaluation. RESULTS:
      Correlation analyses revealed significant association between patient depression
      and WCST Total Perseverations, BRIEF Behavioral Regulation Index (BRI) and family
      stress. Perseverative errors on the WCST and the BRI were found to significantly
      predict depression features in youth with TLE. Patient performance on WCST was
      also found to fully mediate the significant relationship between hippocampal
      sclerosis (HS) and depression in pediatric TLE. Finally, logistic regression
      indicated HS in the presence of TLE was associated with a four-fold risk of
      clinically significant depression ratings. CONCLUSIONS: The current findings
      offer strong support for the relationship between executive function (EF) and
      depression in pediatric TLE. Also, as HS is not modifiable, these findings
      suggest EF intervention may be a potential modality for improving health-related
      quality of life (HRQOL) in youth with TLE. (JINS, 2018, 24, 606-616).

PMID- 29573760
TI  - [Thank You, Reviewers of Acta Medica Portuguesa].

PMID- 29573761
TI  - [2018: It is Time to Move Forward].

PMID- 29573762
TI  - [Gone with the Fire: How Family Physicians in Central Portugal Experienced the
      Aftermath of the Great Fire of October 15, 2017].

PMID- 29573763
TI  - [A Perspective on the OECD Report "Health at a Glance 2017"].

PMID- 29573765
TI  - Risk Factors for the Development of Postembolization Syndrome after Transarterial
      Chemoembolization for Hepatocellular Carcinoma Treatment.
AB  - INTRODUCTION: Hepatic transarterial chemoembolization is a widely used technique
      for the treatment of hepatocellular carcinoma. The most common complication of
      this procedure is postembolization syndrome. The main objective of this study was
      to assess risk factors for the development of postembolization syndrome. MATERIAL
      AND METHODS: Single-centre retrospective analysis of 563 hepatic transarterial
      chemoembolization procedures from January 1st, 2014 - December 31st, 2015.
      Hepatic transarterial chemoembolization was performed with 1/2 - 2 vials of 100 -
      300 MUm microspheres loaded with doxorubicin. Patients who experienced
      postembolization syndrome were identified based on prolongation of
      hospitalization due to pain, fever, nausea and/or vomiting. A control group with
      the patients who did not have postembolization syndrome was randomly created
      (three controls for one case). Descriptive analysis and multivariate logistic
      regression were performed. RESULTS: The overall prevalence of postembolization
      syndrome was 6.2%. Hepatic transarterial chemoembolization with doxorubicin
      dosage above 75 mg (more than one vial), the size of the largest nodule and
      female gender had statistically significant relation with development of
      postembolization syndrome (p = 0.030, p = 0.046 and p = 0.037, respectively).
      DISCUSSION: Doxorrubicin dosage above 75 mg is associated with a higher risk of
      postembolization syndrome. This result can be helpful for decision-making in
      clinical practice, whenever it is possible to avoid a higher dose without
      compromising the efficacy of the treatment. The size of the largest nodule and
      female gender also constitute risk factors for postembolization syndrome. The
      other variables studied were not related to the development of postembolization
      syndrome. CONCLUSION: The dose of doxorrubicin, the size of the largest nodule
      treated and female gender are potential risk factors for the development of
      postembolization syndrome after hepatic transarterial chemoembolization for
      hepatocellular carcinoma.

PMID- 29573764
TI  - Clinical Guidelines and Implementation into Daily Dental Practice.
AB  - INTRODUCTION: The purpose of this study is to assess the extent of the
      familiarity, attitude and perceptions of dental professionals regarding clinical
      dental guidelines and their implementation into daily dental practice. MATERIAL
      AND METHODS: For this purpose, a questionnaire which was developed by the members
      of the World Dental Federation, European Regional Organization Working Group -
      'Relation Between Dental Practitioner and Universities', was implemented by the
      National Dental Associations of six European Regional Organization-zone countries
      (Georgian Stomatological Association - Georgia, Associazione Nazionale Dentisti
      Italiani - Italy, Portuguese Dental Association - Portugal, Russian Dental
      Association - Russia, Swiss Dental Association - Switzerland, and Turkish Dental
      Association - Turkey. The questionnaire was filled by a total of 910 dental
      professionals who are members of one of these national dental associations and
      who voluntarily wanted to participate to this survey. RESULTS: Most of the survey
      participants were familiar with clinical dental guidelines (68%), claimed that
      they implemented them into daily practice (61.7%), and generally acknowledged
      their benefits (81.8%). Many participants believed that clinical dental
      guidelines could help to improve the clinical treatment plan (50.6 %) and the
      accuracy of diagnosis (39.4%); which increased with age and years of practice (p
      < 0.05). The most frequently perceived barrier to the effective implementation of
      clinical dental guidelines was expressed as 'lack of awareness', while
      participants suggested a role for national dental associations in spreading
      clinical dental guidelines. DISCUSSION: A better understanding of the perceptions
      and attitudes of dentists towards clinical dental guidelines and the potential
      impact of factors affecting such perceptions and attitudes may be of particular
      importance for attempts aiming at overcoming the barriers for effective
      implementation of clinical dental guidelines into daily practice. CONCLUSION:
      Despite a significant familiarity and a common positive attitude, dental
      professionals are likely to have different perceptions towards clinical dental
      guidelines, especially regarding their effective implementation into daily
      practice, benefits and barriers.

PMID- 29573766
TI  - [Quality of Life of Children with Otitis Media and Impact of Insertion of
      Transtympanic Ventilation Tubes in a Portuguese Population].
AB  - INTRODUCTION: Quality of life is an important measure for health-outcome
      evaluation. Although otitis media is one of the most common childhood diseases,
      its impact on Portuguese children's quality of life is unknown. The aim of this
      study is to determine the quality of life of Portuguese children with chronic
      otitis media with effusion and/or recurrent acute otitis media and the short-term
      impact of transtympanic ventilation tubes, using the Portuguese version of the OM
      6 questionnaire, a valid, reliable and sensitive instrument to evaluate the
      health-related quality of life in children with otitis media. MATERIAL AND
      METHODS: This study was conducted in a tertiary referral center, to where
      children are referred from primary care and hospital pediatric consultations. The
      Portuguese version of the OM-6 questionnaire was applied to children with chronic
      otitis media with effusion and/or recurrent acute otitis media. The instrument
      was re-administered at two months postoperatively to a group of children who
      underwent tympanostomy tube placement, to evaluate the change in quality of life
      with the surgical procedure. RESULTS: The study involved a sample of 169
      children, aged between 6 months and 12 years (mean: 4.20 +/- 2.05 years). The
      average score in the survey was 3.3 +/- 1.47, of a maximum of 7 (worst quality of
      life). The domains 'caregiver concerns', 'hearing loss' and 'physical suffering'
      had the highest scores. The domain 'hearing loss' was correlated with the domain
      'speech impairment' (rs = 0.41; p < 0.001) and the domain 'physical suffering'
      correlated with the domain 'activity limitation' (rs = 0.47; p < 0.001). There
      was a correlation between the score on 'hearing loss' and the presence of
      conduction hearing loss (chi2 (6) = 24.662; p = 0.022). Children with chronic
      otitis media with effusion had lower scores on the domain 'physical suffering',
      while children with recurrent acute otitis media had lower scores in the domain
      'hearing loss' and higher scores in the domain 'emotional distress'. There was an
      improvement in the quality of life in all the dimensions studied by the
      questionnaire after surgery. The improvement was large in 55%, moderate in 15%
      and small in 10% of the cases. The presence of otorrhea postoperatively did not
      decrease the quality of life improvement achieved with surgery. CONCLUSION:
      Otitis media has a negative impact on Portuguese children quality of life.
      Tympanostomy tubes improve quality of life related to the middle ear in most
      children. The application of validated disease-specific questionnaires allows an
      enhanced understanding of the impact of otitis media on Portuguese children
      quality of life and of the success of therapeutic measures.

PMID- 29573767
TI  - [Mortality from Suicide in the Municipalities of Mainland Portugal: Spatio
      Temporal Evolution between 1980 and 2015].
AB  - INTRODUCTION: Suicide is considered a public health priority. It is a complex
      phenomenon resulting from the interaction of several factors, which do not depend
      solely on individual conditions. This study analyzes the spatio-temporal
      evolution of suicide mortality between 1980 and 2015, identifying areas of high
      risk, and their variation, in the 278 municipalities of Continental Portugal.
      MATERIAL AND METHODS: Based on the number of self-inflicted injuries and deaths
      from suicide and the resident population, the spatio-temporal evolution of the
      suicide mortality rate was assessed via: i) a Poisson joinpoint regression model,
      and ii) spatio-temporal clustering methods. RESULTS: The suicide mortality rate
      evolution showed statistically significant increases over three periods (1980 -
      1984; 1999 - 2002 and 2006 - 2015) and two statistically significant periods of
      decrease (1984 - 1995 and 1995 - 1999). The spatio-temporal analysis identified
      five clusters of high suicide risk (relative risk >1) and four clusters of low
      suicide risk (relative risk < 1). DISCUSSION: The periods when suicide mortality
      increases seem to overlap with times of economic and financial instability. The
      geographical pattern of suicide risk has changed: presently, the suicide rates
      from the municipalities in the Center and North are showing more similarity with
      those seen in the South, thus increasing the ruralization of the phenomenon of
      suicide. CONCLUSION: Between 1980 and 2015 the spacio-temporal pattern of
      mortality from suicide has been changing and is a phenomenon that is currently
      experiencing a growing trend (since 2006) and is of higher risk in rural areas.

PMID- 29573768
TI  - Factors Influencing the Implementation of Screening and Brief Interventions for
      Alcohol Use in Primary Care Practices: A Systematic Review Protocol.
AB  - INTRODUCTION: Alcohol is a leading risk factor contributing to the global burden
      of disease. National and international agencies recommend evidence-based
      screening and brief interventions in primary care settings in order to reduce
      alcohol consumption. However, the majority of primary care professionals do not
      routinely deliver such interventions. OBJECTIVE: To identify factors influencing
      general practitioners/family physicians' and primary care nurses' routine
      delivery of alcohol screening and brief intervention in adults. MATERIAL AND
      METHODS: A systematic literature search will be carried out in the following
      electronic databases: Medline, CINAHL, CENTRAL, and PsycINFO. Two authors will
      independently abstract data and assess study quality using the NIH National
      Heart, Lung, and Blood Institute quality assessment tools for quantitative
      studies, and the CASP checklist for qualitative studies. A narrative synthesis of
      the findings will be provided, structured around the barriers and facilitators
      identified. Identified barriers and facilitators will be further analysed using
      the Behavioural Change Wheel/Theoretical Domains Framework. DISCUSSION: This
      review will describe the barriers to, and facilitators for, the implementation of
      alcohol screening and brief interventions by general practitioners/family
      physicians and nurses at primary care practices. By mapping the barriers and
      facilitators to the domains of the Behavioural Change Wheel/Theoretical Domains
      Framework, this review will also provide implementation researchers with a useful
      tool for selecting promising practitioner-oriented behavioural interventions for
      improving alcohol screening and brief intervention delivery in primary care.
      CONCLUSION: This review will provide important information for implementing
      alcohol screening and brief intervention in primary health care.Systematic Review
      Registration: PROSPERO CRD42016052681.

PMID- 29573769
TI  - [Delirium: The 7th Vital Sign?]
AB  - INTRODUCTION: Delirium is an acute, transient and fluctuating neuropsychiatric
      syndrome that is common in medical wards, particularly in the geriatric and
      palliative care population. MATERIAL AND METHODS: We present a brief literature
      review of the definition, pathophysiology, aetiology, diagnosis, prevention and
      treatment of delirium and its social and economic impact. RESULTS AND DISCUSSION:
      Delirium is under-recognized, especially by health professionals, and is
      associated with higher morbidity, mortality and economic burden. Moreover, the
      presence of delirium interferes with the evaluation and approach to other
      symptoms. Furthermore, it causes significant distress in patient's families and
      health professionals. The best treatment for delirium is prevention which is
      based on multidisciplinary interventions that addresses the main risk factors.
      The scientific evidence for the treatment of delirium is scarce. Non
      pharmacological approaches are usually the first choice, and includes
      environmental, behavioural and social strategies. Pharmacological options, mainly
      antipsychotics, are a second-line treatment used essentially to prevent self
      harm. CONCLUSION: The recognition and prevention of delirium are crucial. Health
      professional education and training, patient clinical monitoring and families
      support are mandatory. Considering the impact of delirium on patients, relatives,
      health services and professionals we must be more aware of delirium and, why not,
      make it the 7th vital sign.

PMID- 29573770
TI  - [Hidradenitis Suppurativa: Combined Treatment with Dermal Template, Skin Graft
      and Negative Pressure Wound Therapy, a Case Study].
AB  - Hidrosadenitis supurativa is a chronic inflammatory disease with great physical
      and psychological impact. Although conservative treatments may be effective in
      mild forms of the disease, extensive surgical resection and reconstruction are
      necessary in more severe forms of the disease. The purpose of this paper is to
      describe our two-stage reconstructive procedure regarding this kind of disease.
      We present a clinical case of a patient with severe, bilateral axillary
      hidrosadenitis. In the first surgical step we excised the lesions and applied the
      artificial dermis secured with negative pressure wound therapy. In the second
      step we used a split thickness skin graft to close the wound and again applied
      negative pressure wound therapy. The graft take was very good, without
      complications. The cosmetic outcome is acceptable and shoulder mobility was not
      compromised. No recurrence was detected (nine months follow up).

PMID- 29573771
TI  - Radiofrequency for Treatment of Refractory Epistaxis in Hereditary Hemorrhagic
      Telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia is a rare multi-systemic autosomal dominant
      disorder characterized by dysplasia of the vascular connective tissue and
      recurrent bleeding tendency. Epistaxis is the most common and earliest symptom.
      It is usually mild to moderate, however, in some patients it can be severe with
      significant interference in quality of life. We report a case of a patient with
      hereditary hemorrhagic telangiectasia, in which an episode of refractory
      epistaxis was treated with radiofrequency and fibrin sealant. Control of acute
      bleeding and elimination of telangiectasia was possible with this technique.
      After six months follow-up, there was no epistaxis recurrence. Various treatments
      for epistaxis in this disease have been described in the literature, but there is
      no consensus about the gold-standard procedure. Radiofrequency ablation of
      telangiectasia is a recent technique that has shown to be safe, effective and
      well tolerated, even in patients who underwent other previous treatments.

PMID- 29573772
TI  - Pneumatocele, Pneumocephalus or Aerocele.

PMID- 29573773
TI  - Congenital Hip Dislocation: A Rare Case in Adulthood.

PMID- 29573774
TI  - Letter to the Editor: Infectious Mononucleosis and Cholestatic Hepatitis.

PMID- 29573775
TI  - [Letter to the Editor. Use of Vitamin K Antagonists in Patients on Hemodialysis:
      Is Benefit Greater than the Risk?]

PMID- 29573776
TI  - WITHDRAWN: Commentary to accompany "After motor vehicle accidents is it thoracic
      outlet syndrome or ulnar entrapment syndrome? How to make the correct diagnosis".
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- 29573777
TI  - Perioperative blood transfusion and short-term outcomes after major abdominal
      operations.

PMID- 29573778
TI  - Long-term Progression of Type 1 Neovascularization in Age-related Macular
      Degeneration Using Optical Coherence Tomography Angiography.

PMID- 29573779
TI  - Choroidal Changes After Suprachoroidal Injection of Triamcinolone in Eyes With
      Macular Edema Secondary to Retinal Vein Occlusion.

PMID- 29573780
TI  - Foreword.

PMID- 29573781
TI  - Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell
      carcinomas.
AB  - BACKGROUND AND OBJECTIVES: We have previously indicated that EGFR has a role in
      carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In
      addition, EGFR activates 2 of the most important intracellular signalling
      pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study
      was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its
      relationship with clinical-pathological parameters and follow-up of sinonasal
      squamous cell carcinoma. MATERIAL AND METHODS: The immunohistochemical expression
      of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship
      with various clinical-pathological parameters was studied in a series of 54
      patients with SNSCC. RESULTS: Loss of PTEN expression was observed in 33/54 cases
      (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%),
      8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression
      was related to intracranial invasion and development of regional metastases
      (p=0.005). Overexpression of pS6 was associated with a decrease in survival
      (p=0.008), presence of local recurrences (p=0.055), and worsening of overall
      prognosis (p=0.007). No significant relationships were observed between pAKT and
      mTOR expression and the clinicopathological parameters studied. CONCLUSIONS:
      Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are
      common in a subgroup of SNSCC. This study reveals that the absence of pS6
      overexpression is associated with better clinical outcomes. Therefore, pS6
      expression could be considered as an unfavourable prognostic marker.

PMID- 29573782
TI  - ASGE guideline for infection control during GI endoscopy.

PMID- 29573783
TI  - Development of a fast and simple gas chromatographic protocol based on the
      combined use of alkyl chloroformate and solid phase microextraction for the assay
      of polyamines in human urine.
AB  - Polyamines are aliphatic amines with low molecular weight that are widely
      recognized as one of the most important cancer biomarkers for early diagnosis and
      treatment. The goal of the work herein presented is the development of a rapid
      and simple method for the quantification of free polyamines (i.e., putrescine,
      cadaverine, spermidine, spermine) and N-monoacetylated polyamines (i.e., N1
      Acetylspermidine, N8-Acetylspermidine, and N1-Acetylspermine) in human urine. A
      preliminary derivatization with propyl chloroformate combined with the use of
      solid phase microextraction (SPME) allowed for an easy and automatable protocol
      involving minimal sample handling and no consumption of organic solvents. The
      affinity of the analytes toward five commercial SPME coatings was evaluated in
      univariate mode, and the best result in terms of analyte extraction was achieved
      using the divinylbenzene/carboxen/polydimethylsiloxane fiber. The variables
      affecting the performance of SPME analysis were optimized by the multivariate
      approach of experimental design and, in particular, using a central composite
      design (CCD). The optimal working conditions in terms of response values are the
      following: extraction temperature 40  degrees C, extraction time of 15 min and no
      addition of NaCl. Analyses were carried out by gas chromatography-triple
      quadrupole mass spectrometry (GC-QqQ-MS) in selected reaction monitoring (SRM)
      acquisition mode. The developed method was validated according to the guidelines
      issued by the Food and Drug Administration (FDA). The satisfactory performances
      reached in terms of linearity, sensitivity (LOQs between 0.01 and 0.1 MUg/mL),
      matrix effect (68-121%), accuracy, and precision (inter-day values between -24%
      and +16% and in the range 3.3-28.4%, respectively) make the proposed protocol
      suitable to be adopted for quantification of these important biomarkers in urine
      samples.

PMID- 29573784
TI  - Supercritical fluid chromatography versus high performance liquid chromatography
      for enantiomeric and diastereoisomeric separations on coated polysaccharides
      based stationary phases: Application to dihydropyridone derivatives.
AB  - For analytical applications, SFC has always remained in the shadow of LC.
      Analytical enantioseparation of eight dihydropyridone derivatives, was run in
      both High Performance Liquid Chromatography and Supercritical Fluid
      Chromatography. Four polysaccharide based chiral stationary phases namely amylose
      and cellulose tris(3, 5-dimethylphenylcarbamate), amylose tris((S)-alpha
      phenylethylcarbamate) and cellulose tris(4-methylbenzoate) with four mobile
      phases consisted of either n-hexane/ethanol or propan-2-ol (80:20 v:v) or carbon
      dioxide/ethanol or propan-2-ol (80:20 v:v) mixtures were investigated under same
      operatory conditions (temperature and flow-rate). The elution strength,
      enantioselectivity and resolution were compared in the two methodologies. For
      these compounds, for most of the conditions, HPLC afforded shorter retention
      times and a higher resolution than SFC. HPLC appears particularly suitable for
      the separation of the compounds bearing two chiral centers. For instance compound
      7 was baseline resolved on OD-H CSP under n-Hex/EtOH 80/20, with resolution
      values equal to 2.98, 1.55, 4.52, between the four stereoisomers in less than 17
      min, whereas in SFC, this latter is not fully separated in 23 min under similar
      eluting conditions. After analytical screenings, the best conditions were
      transposed to semi-preparative scale.

PMID- 29573785
TI  - Upregulation of alveolar neutrophil enzymes and long pentraxin-3 in human chronic
      lung allograft dysfunction subtypes.

PMID- 29573786
TI  - What the radiologist should know about postoperative MDCT evaluation of a patient
      treated with cytoreductive surgery with or without hyperthermic intraperitoneal
      chemotherapy.
AB  - Cytoreductive surgery (CRS), often associated with hyperthermic intraperitoneal
      chemotherapy (HIPEC), is now a well-recognised treatment for most peritoneal
      malignancies in selected patients. As imaging is frequently performed
      postoperatively, radiologists are increasingly confronted with postoperative
      multidetector-row computed tomography (MDCT) examinations in these cases. In this
      article, after briefly describing the procedures that are currently being
      performed for the treatment of peritoneal metastases, the normal postoperative
      MDCT changes that may be encountered after these procedures are described. We
      then highlight complications that may arise after CRS, depending on the surgery
      performed, and those related to HIPEC, and illustrate their MDCT features.

PMID- 29573787
TI  - Tumour motion of oesophageal squamous cell carcinoma evaluated by cine MRI:
      associated with tumour location.
AB  - AIM: To evaluate the association between oesophageal tumour motion and tumour
      location using cine magnetic resonance imaging (MRI). MATERIALS AND METHODS:
      Thirty-three consecutive patients with oesophageal squamous cell carcinoma were
      enrolled, and underwent cine MRI of oesophageal tumours. The maximum
      displacements in the anterior-posterior (A-P), superior-inferior (S-I), and left
      right (L-R) directions of the tumours were assessed statistically to show their
      associations with tumour location. RESULTS: Tumour motion in A-P and S-I
      directions increased from upper to lower oesophagus (r=0.505, p=0.003; and
      r=0.600, p<0.001, respectively). In A-P and S-I directions, tumours showed larger
      motion in the lower oesophagus than in the upper or middle oesophagus (all
      p<0.05). Motion of middle and lower oesophageal tumours in the S-I direction was
      larger than in L-R or A-P direction (all p<0.05). To provide 95% geometric
      coverage for the motion of upper oesophageal tumours, statistical analysis showed
      margins of 3.75 mm in L-R direction, 3.72 mm in A-P direction, and 5.38 mm in S-I
      direction. For the motion of tumours of the middle oesophagus, 95% coverage
      required margins of 8.50, 6.62, and 11.96 mm in L-R, A-P, and S-I directions,
      respectively, and for lower oesophageal tumours, 95% coverage required margins of
      9.17, 9.68, and 12.98 mm in L-R, A-P, and S-I direction, respectively.
      CONCLUSION: Oesophageal tumour motion in different directions can be associated
      with tumour location as shown on cine MRI, suggesting that the present findings
      could be helpful for better understanding oesophageal tumour motion and gating
      individualised radiation delivery strategies.

PMID- 29573788
TI  - Enhanced recovery after esophageal resection.
AB  - ERAS is a multimodal perioperative care program which replaces traditional
      practices concerning analgesia, intravenous fluids, nutrition, mobilization as
      well as a number of other perioperative items, whose implementation is supported
      by evidence-based best practices. According to the RICA guidelines published in
      2015, a review of the literature and the consensus established at a
      multidisciplinary meeting in 2015, we present a protocol that contains the basic
      procedures of an ERAS pathway for resective esophageal surgery. The measures
      involved in this ERAS pathway are structured into 3areas: preoperative,
      perioperative and postoperative. The consensus document integrates all the
      analyzed items in a unique time chart. ERAS programs in esophageal resection
      surgery can reduce postoperative morbidity, mortality, hospitalization and
      hospital costs.

PMID- 29573789
TI  - Alpha 1-antitrypsin inhibits microglia activation and facilitates the survival of
      iPSC grafts in hypertension mouse model.
AB  - This study was conducted to investigate the use of Alpha 1-antitrypsin (AAT) to
      inhibit microglia activation in chronic hypertension model and provide a
      permissive environment for stem cell transplantation. Chronic ocular hypertension
      of C57BL/6 mice using magnetic microbead injection was induced 3 weeks prior to
      iPSCs transplantation. The ocular hypertension model was assessed histologically
      and intraocular pressure was measured. Survival of grafted cells and microglia
      activation were examined by flow cytometry and immunofluorescence in AAT and PBS
      treated hosts. Retinal cytokines expression was also detected by real-time PCR.
      Chronic ocular hypertension resulted in persistent microglia activation and stem
      cell grafts loss. AAT treatment significantly inhibited microglia activation and
      facilitated the survival of transplant iPSCs 4w post transplantation compared to
      PBS treatment. AAT holds tremendous potential for the clinical application to
      control neuroinflammation factor in glaucoma and improve the stem cell
      replacement therapy of retinal neurodegenerative disease.

PMID- 29573790
TI  - [Market access agreements: Definition and features. Could MAA be defined as a
      solution for immunotherapy funding by French health system?]
AB  - Over the last few years, many therapeutic innovations have been approved and
      marketed in France, within a strained financial setting. Legal dispositions
      allowed manufacturers (LEEM - les enterprises du medicament) and the economic
      committee for health products (CEPS) to contract various confidential market
      access agreements to contain health product expenses. The purposes of this
      article are to define and describe these different existing market access
      agreements and to open discussion on their applicability to the problematic of
      immune-oncology drugs financing. Financial agreements, which led to major savings
      (discounts refunded to the public payer), have not responded completely to the
      therapeutic innovations financing problems. Performance agreements (funding based
      on real-life data and effectiveness of the drug) constitute a hope for health
      products financing, but major methodological challenges for their use in routine
      restrict them to rare cases only today. Even though several financial agreements
      could partly respond to this problematic, use of performance agreements could
      really constitute an interesting track to tackle this issue.

PMID- 29573791
TI  - Understanding the Molecular Mechanisms Underpinning Gene by Environment
      Interactions in Psychiatric Disorders: The FKBP5 Model.
AB  - Epidemiologic and genetic studies suggest common environmental and genetic risk
      factors for a number of psychiatric disorders, including depression, bipolar
      disorder, and schizophrenia. Genetic and environmental factors, especially
      adverse life events, not only have main effects on disease development but also
      may interact to shape risk and resilience. Such gene by adversity interactions
      have been described for FKBP5, an endogenous regulator of the stress
      neuroendocrine system, conferring risk for a number of psychiatric disorders. In
      this review, we present a molecular and cellular model of the consequences of
      FKBP5 by early adversity interactions. We illustrate how altered genetic and
      epigenetic regulation of FKBP5 may contribute to disease risk by covering
      evidence from clinical and preclinical studies of FKBP5 dysregulation, known cell
      type and tissue-type expression patterns of FKBP5 in humans and animals, and the
      role of FKBP5 as a stress-responsive molecular hub modulating many cellular
      pathways. FKBP5 presents the possibility to better understand the molecular and
      cellular factors contributing to a disease-relevant gene by environment
      interaction, with implications for the development of biomarkers and
      interventions for psychiatric disorders.

PMID- 29573792
TI  - In situ comparison of A-mode ultrasound tracking system and skin-mounted markers
      for measuring kinematics of the lower extremity.
AB  - Skin-mounted marker based motion capture systems are widely used in measuring the
      movement of human joints. Kinematic measurements associated with skin-mounted
      markers are subject to soft tissue artifacts (STA), since the markers follow skin
      movement, thus generating errors when used to represent motions of underlying
      bone segments. We present a novel ultrasound tracking system that is capable of
      directly measuring tibial and femoral bone surfaces during dynamic motions, and
      subsequently measuring six-degree-of-freedom (6-DOF) tibiofemoral kinematics. The
      aim of this study is to quantitatively compare the accuracy of tibiofemoral
      kinematics estimated by the ultrasound tracking system and by a conventional skin
      mounted marker based motion capture system in a cadaveric experimental scenario.
      Two typical tibiofemoral joint models (spherical and hinge models) were used to
      derive relevant kinematic outcomes. Intra-cortical bone pins equipped with
      optical markers were inserted in the tibial and femoral bones to serve as a
      reference to provide ground truth kinematics. The ultrasound tracking system
      resulted in lower kinematic errors than the skin-mounted markers (the ultrasound
      tracking system: maximum root-mean-square (RMS) error 3.44 degrees  for rotations
      and 4.88 mm for translations, skin-mounted markers with the spherical joint
      model: 6.32 degrees  and 6.26 mm, the hinge model: 6.38 degrees  and 6.52 mm).
      Our proposed ultrasound tracking system has the potential of measuring direct
      bone kinematics, thereby mitigating the influence and propagation of STA.
      Consequently, this technique could be considered as an alternative method for
      measuring 6-DOF tibiofemoral kinematics, which may be adopted in gait analysis
      and clinical practice.

PMID- 29573793
TI  - Effect of stable and unstable load carriage on walking gait variability, dynamic
      stability and muscle activity of older adults.
AB  - Load carriage perturbs the neuromuscular system, which can be impaired due to
      ageing. The ability to counteract perturbations is an indicator of neuromuscular
      function but if the response is insufficient the risk of falls will increase.
      However, it is unknown how load carriage affects older adults. Fourteen older
      adults (65 +/- 6 years) attended a single visit during which they performed 4 min
      of walking in 3 conditions, unloaded, stable backpack load and unstable backpack
      load. During each walking trial, 3-dimensional kinematics of the lower limb and
      trunk movements and electromyographic activity of 6 lower limb muscles were
      recorded. The local dynamic stability (local divergence exponents), joint angle
      variability and spatio-temporal variability were determined along with muscle
      activation magnitudes. Medio-lateral dynamic stability was lower (p = 0.018) and
      step width (p = 0.019) and step width variability (p = 0.015) were greater in
      unstable load walking and step width variability was greater in stable load
      walking (p = 0.009) compared to unloaded walking. However, there was no effect on
      joint angle variability. Unstable load carriage increased activity of the Rectus
      Femoris (p = 0.001) and Soleus (p = 0.043) and stable load carriage increased
      Rectus Femoris activity (p = 0.006). These results suggest that loaded walking
      alters the gait of older adults and that unstable load carriage reduces dynamic
      stability compared to unloaded walking. This can potentially increase the risk of
      falls, but also offers the potential to use unstable loads as part of fall
      prevention programmes.

PMID- 29573794
TI  - The effect of static neck flexion on mechanical and neuromuscular behaviors of
      the cervical spine.
AB  - Occupations that involve sustained or repetitive neck flexion are associated with
      a higher incidence of neck pain. Little in vivo information is available on the
      impact of static neck flexion on cervical spinal tissue. The aim of this study
      was to assess changes in mechanical and neuromuscular behaviors to sustained neck
      flexion in healthy adults. Sixty healthy subjects aged 20-35 years participated
      in this study. The participants were exposed to static neck flexion at a fixed
      angle of full flexion for 10 min. Mechanical and neuromuscular responses of the
      cervical spine to sudden perturbations were measured pre- and post-exposure.
      Magnitude of load-relaxation during flexion exposure, stiffness, peak head
      angular velocity, and reflexive activities of cervical muscles were recorded.
      Effective neck stiffness decreased significantly, especially in female
      participants (P = 0.0001). The reflexive response of the cervical erector spinae
      muscles to head perturbation delayed significantly (P = 0.0001). Peak head
      angular velocity was significantly increased after exposure to neck flexion for
      10 min, especially in female participants (P = 0.001). In the present study,
      static flexion resulted in changes in mechanical and neuromuscular behavior of
      the cervical spine, potentially leading to decreased stiffness of the cervical
      spine. The results confirm the importance of maintaining a correct head and neck
      position during work and improving the work environment to reduce the cervical
      spinal load and work-related neck pain.

PMID- 29573795
TI  - Effects of gamma radiation on microbial, physicochemical, and structural
      properties of whey protein model system.
AB  - Gamma radiation has been used in food processing for many years, though it has
      certain effects on food components. Whey protein solutions (10%/30%, wt/vol) were
      treated with gamma radiation at various dosages (10-25 kGy) and evaluated for
      microbial changes in the solutions and physicochemical and structural changes of
      whey proteins. Whey protein solutions after gamma radiation showed substantially
      lower populations of all viable microorganisms than those of controls. The 10%
      whey protein solution treated at radiation of 20 or 25 kGy remained sterile for
      up to 4 wk at room temperature. Gamma radiation increased viscosity and turbidity
      and decreased soluble nitrogen of whey protein solutions compared to nonradiated
      control samples regardless of radiation dosage. Nonreducing sodium dodecyl
      sulfate-PAGE suggested that whey proteins under gamma radiation treatment formed
      aggregates with high molecular weights. Reducing sodium dodecyl sulfate-PAGE
      showed that disulfide bonds played a role in gamma radiation-induced whey protein
      cross-linking. Scanning and transmission electron microscopy micrographs
      exhibited large aggregates of whey proteins after gamma radiation treatment.
      Results suggested that gamma radiation could be applied to whey protein solution
      for purposes of reducing microbial counts and cross-linking protein molecules.

PMID- 29573796
TI  - Evaluation of alternatives to cautery disbudding of dairy goat kids using
      physiological measures of immediate and longer-term pain.
AB  - We evaluated alternatives to cautery disbudding of goat kids using physiological
      measures of immediate and longer-term pain. Fifty Saanen doe kids were randomly
      assigned to 1 of 5 treatments (n = 10/treatment): (1) cautery disbudding (CAUT),
      (2) caustic paste disbudding (CASP), (3) liquid nitrogen disbudding (CRYO), (4)
      clove oil injected into the horn bud (CLOV), or (5) sham disbudding (SHAM). Serum
      cortisol and haptoglobin concentrations were measured from blood samples
      collected immediately before treatment (baseline) and at 15, 30, 60, and 120 min
      and then again at 6 and 24 h post-treatment. An infrared thermography camera was
      used to take images of the horn buds 24 h pre- and 24, 48, and 72 h post
      treatment to measure skin temperature. Body weight was measured daily for 1 wk to
      assess weight change post-treatment. Images of the horn buds were taken at d 1,
      2, and 7 and at 6 wk post-treatment to assess tissue damage and wound healing.
      Mean cortisol concentrations were elevated in CASP kids 1 h post-treatment
      relative to CAUT kids. Cortisol concentrations of CRYO kids were higher than
      those of CAUT kids 30 min post-treatment; concentrations for CLOV kids were
      similar to CAUT kids post-treatment. Mean haptoglobin concentrations were similar
      across treatments over time; however, CLOV kids had higher concentrations at 24 h
      post-treatment than all other treatments. Skin temperatures of CASP and CLOV kids
      were elevated relative to CAUT kids at all time points post-treatment, and all
      disbudded kids had skin temperatures above those of SHAM kids at 72 h post
      treatment. Treatment did not influence weight gain. The CAUT kids had large, open
      wounds exposing bone; small scabs were still evident 6 wk post-treatment. The
      CASP kids had red and open, raw wounds that generated large eschars, apparent for
      up to 6 wk. The CRYO kids had closed, dry wounds initially, but over time lesions
      appeared that caused open wounds; small scabs were present 6 wk post-treatment.
      The CLOV kids had closed, dry wounds with blackened skin; healed skin and minimal
      scabs were present 6 wk post-treatment. Caustic paste and cryosurgical disbudding
      appeared to cause more pain compared with cautery disbudding; thus, these methods
      may not provide good alternatives to cautery disbudding. Clove oil appeared to
      cause a similar pain response as cautery disbudding and smaller wounds with
      earlier tissue repair; this method shows promise as an alternative to cautery
      disbudding.

PMID- 29573797
TI  - Genome-wide association mapping for type and mammary health traits in French
      dairy goats identifies a pleiotropic region on chromosome 19 in the Saanen breed.
AB  - Type traits and mammary health traits are important to dairy ruminant breeding
      because they influence animal health, milking ability, and longevity, as well as
      the economic sustainability of farms. The availability of the genomic sequence
      and a single nucleotide polymorphism chip in goats has opened up new fields of
      investigation to better understand the genes and mechanisms that underlie such
      complex traits and to be able to select them. Our objective was to perform a
      genome-wide association study in dairy goats for 11 type traits and somatic cell
      count (SCC) as proxies for mastitis resistance. A genome-wide association study
      was implemented using a daughter design composed of 1,941 Alpine and Saanen goats
      sired by 20 artificial insemination bucks, genotyped with the Illumina GoatSNP50
      BeadChip (Illumina Inc., San Diego, CA). This association study was based on both
      linkage analyses and linkage disequilibrium using QTLmap software
      (http://dga7.jouy.inra.fr/qtlmap/) interval mapping was performed with the
      likelihood ratio test using linear regressions. Breeds were analyzed together and
      separately. The study highlighted 37 chromosome-wide significant quantitative
      trait loci (QTL) with linkage analyses and 222 genome-wide significant QTL for
      linkage disequilibrium, for type and SCC traits in dairy goats. Genomic control
      of those traits was mostly polygenic and breed-specific, suggesting that within
      breed selection would be favored for those traits. Of note, Capra hircus autosome
      (CHI) 19 appeared to be highly enriched in single nucleotide polymorphisms
      associated with type and SCC, with 2 highly significant regions in the Saanen
      breed. One region (33-42 Mb) was significantly associated with SCC and includes
      candidate genes associated with response to intramammary infections (RARA, STAT3,
      STAT5A, and STAT5B). Another region of the CHI 19 (24.5-27 Mb) exhibited an
      adverse pleiotropic effect on milk production (milk, fat yield, and protein
      yield) and udder traits (udder floor position and rear udder attachment) that
      agreed with the negative genetic correlations that exist between those 2 groups
      of traits. These QTL were not found in the Alpine breed. In Alpine, the 2 most
      significant regions were associated with chest depth on CHI 6 (45.8-46.0 Mb) and
      CHI 8 (80.7-81.1 Mb). These results will be helpful for goat selection in the
      future and could lead to identification of causal mutations.

PMID- 29573798
TI  - Nuclear factor erythroid 2-related factor 2 antioxidant response element pathways
      protect bovine mammary epithelial cells against H2O2-induced oxidative damage in
      vitro.
AB  - The experiment was conducted to determine the role of nuclear factor (erythroid
      derived 2)-like factor 2 (NFE2L2, formerly Nrf2) antioxidant response element
      (ARE) pathway in protecting bovine mammary epithelial cells (BMEC) against H2O2
      induced oxidative stress injury. An NFE2L2 small interfering RNA (siRNA)
      interference or a pCMV6-XL5-NFE2L2 plasmid fragment was transfected to
      independently downregulate or upregulate expression of NFE2L2. Isolated BMEC in
      triplicate were exposed to H2O2 (600 MUM) for 6 h to induce oxidative stress
      before transient transfection with scrambled siRNA, NFE2L2-siRNA, pCMV6-XL5, and
      pCMV6-XL5-NFE2L2. Cell proliferation, apoptosis and necrosis rates, antioxidant
      enzyme activities, reactive oxygen species (ROS) and malondialdehyde (MDA)
      production, protein and mRNA expression of NFE2L2 and downstream target genes,
      and fluorescence activity of ARE were measured. The results revealed that
      compared with the control, BMEC transfected with NFE2L2-siRNA3 had proliferation
      rates that were 9 or 65% lower without or with H2O2, respectively. These cells
      also had apoptosis and necrosis rates that were 27 and 3.5 times greater with
      H2O2 compared with the control group, respectively. In contrast, transfected
      pCMV6-XL5-NFE2L2 had proliferation rates that were 64.3% greater or 17% lower
      without or with H2O2 compared with the control group, respectively. Apoptosis
      rates were 1.8 times lower with H2O2 compared with the control. In addition,
      compared with the control, production of ROS and MDA and activities of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione
      S-transferase (GST) increased markedly in cells transfected with pCMV6-XL5-NFE2L2
      and without H2O2. However, compared with the control, production of ROS and MDA
      and activity of CAT and GSH-Px increased markedly, whereas activities of SOD and
      GST decreased in cells transfected with pCMV6-XL5-NFE2L2 and incubated with H2O2.
      Compared with the control, cells transfected with NFE2L2-siRNA3 with or without
      H2O2 had lower production of ROS and MDA and activity of SOD, CAT, GSH-Px, and
      GST. Cells transfected with pCMV6-XL5-NFE2L2 with or without H2O2 had markedly
      higher protein and mRNA expression of NFE2L2, heme oxygenase-1 (HMOX-1), NADH
      quinone oxidoreductase 1, glutamate cysteine ligase catalytic subunit, and
      glutamyl cystine ligase modulatory subunit compared with the control incubations.
      Cells transfected with NFE2L2-siRNA3 without or with H2O2 had markedly lower
      protein and mRNA expression of NFE2L2, HMOX-1, NADH quinone oxidoreductase 1,
      glutamyl cystine ligase modulatory subunit, and glutamate-cysteine ligase
      catalytic subunit compared with the control incubations. In addition, expression
      of HMOX-1 was 5.3-fold greater with H2O2 compared with the control. Overall,
      results indicate that NFE2L2 plays an important role in the NFE2L2-ARE pathway
      via the control of HMOX-1. The relevant mechanisms in vivo merit further study.

PMID- 29573799
TI  - Metabotypes with elevated protein and lipid catabolism and inflammation precede
      clinical mastitis in prepartal transition dairy cows.
AB  - Clinical mastitis (CM), the most prevalent and costly disease in dairy cows, is
      diagnosed most commonly shortly after calving. Current indicators do not
      satisfactorily predict CM. This study aimed to develop a robust and comprehensive
      mass spectrometry-based metabolomic and lipidomic workflow using untargeted ultra
      performance liquid chromatography high-resolution mass spectrometry for
      predictive biomarker detection. Using a nested case-control design, we measured
      weekly during the prepartal transition period differences in serum metabolites,
      lipids, inflammation markers, and minerals between clinically healthy Holstein
      dairy cows diagnosed with mastitis postcalving (CMP; n = 8; CM diagnosis d 1 = 3
      cows, d 2 = 2 cows, d 4 = 1 cow; d 25 = 1 cow, and d 43 = 1 cow that had
      subclinical mastitis since d 3) or not (control; n = 9). The largest fold
      differences between CMP and control cows during the prepartal transition period
      were observed for 3'-sialyllactose in serum. Seven metabolites (N
      methylethanolamine phosphate, choline, phosphorylcholine, free carnitine,
      trimethyl lysine, tyrosine, and proline) and 3 metabolite groups (carnitines, AA
      metabolites, and water-soluble phospholipid metabolites) could correctly classify
      cows for their future CM status at both 21 and 14 d before calving. Biochemical
      analysis using lipid and metabolite-specific commercial diagnostic kits supported
      our mass spectrometry-based omics results and additionally showed elevated
      inflammatory markers (serum amyloid A and visfatin) in CMP cows. In conclusion,
      metabolic phenotypes (i.e., metabotype) with elevated protein and lipid
      metabolism and inflammation may precede CM in prepartal transition dairy cows.
      The discovered serum metabolites and lipids may assist in predictive diagnostics,
      prevention strategies, and early treatment intervention against CM, and thereby
      improve cow health and welfare.

PMID- 29573800
TI  - Short communication: The effect of novel antiseptic compounds on umbilical cord
      healing and incidence of infection in dairy calves.
AB  - The goal of dipping the umbilical cord after birth in calves is to promote
      healing of the umbilical stump, prevent infection, and encourage the umbilical
      tissue to detach from the body. Treatment applied to the umbilical area is an
      important management step for preventing morbidity and mortality in calves. The
      objective of this study was to compare the effect of 4 umbilical dips on the
      healing rate, incidence of infection, and age at umbilical cord detachment using
      newborn Holstein heifer calves (n = 73). Calves were alternately assigned by
      birth order to 4 treatment groups: 7% iodine, a dry dip formulated using an
      antibacterial peptide (nisin) mixed with talc (3.105 g of nisin per 100 g of
      talcum powder on a weight per weight basis), liquid nisin (64 ug/mL), and 4%
      chlorhexidine mixed with alcohol in a 50:50 solution. Umbilical cords were dipped
      30 min after birth. Before initial dipping, umbilical cord diameter (as an
      indicator of the rate of cord drying and healing rate) was determined using a
      digital caliper. The caliper measurements were repeated at 24 +/- 1, 48 +/- 1,
      and 72 +/- 1 h (+/-standard deviation) of age and were continued daily until the
      umbilical cord healed and detached from the animal's body. Diagnosed umbilical
      infections were documented by veterinary staff based on a combination of clinical
      symptoms (redness, swelling, purulent discharge, painful response (flinch or
      kicking) to palpation of the umbilical stump) in addition to a lack of appetite
      and fever. Data were analyzed using MIXED model procedures with fixed effect of
      umbilical treatment. No treatment differences were noted between dips on the
      umbilical cord drying rate or days for umbilical cord to detach. Treatment
      effects were observed on incidence of umbilical infection (incidence of infection
      for calves across all treatments was 9.0%).

PMID- 29573801
TI  - Elimination of experimentally induced bovine intramammary infection assessed by
      multiplex real-time PCR and bacterial culture.
AB  - Diagnosis of bovine intramammary infection (IMI) has traditionally been based on
      bacterial culture, but currently IMI can also be detected with DNA based methods,
      such as multiplex real-time PCR. The aim of this study was to describe the
      elimination of bacteria in experimentally induced IMI on the quarter level, using
      conventional bacterial culture (BC) and multiplex real-time PCR. Two coagulase
      negative staphylococcal species, Staphylococcus epidermidis and Staphylococcus
      simulans, were experimentally inoculated into 14 healthy quarters of 8 dairy cows
      during 4 consecutive study periods. Intramammary infections were followed with 20
      milk samplings per each quarter. Milk somatic cell count was monitored to
      evaluate the inflammation process in the quarters. Four quarters cured
      spontaneously during the study period according to the culture. The PCR detected
      staphylococcal DNA from these quarters for several days after they were defined
      as cured in BC. Agreement between BC and PCR results varied from substantial to
      almost perfect agreement for the first 36 h postchallenge, decreasing to moderate
      levels toward the end of the sampling period. Based on this study, we recommend
      collecting possible follow-up samples to assess the bacteriological cure from IMI
      not until 2 to 3 wk after the onset of mastitis or after the quarter milk somatic
      cell count has normalized when PCR is used.

PMID- 29573802
TI  - Milk nutrition and childhood epilepsy: An ex vivo study on cytokines and
      oxidative stress in response to milk protein fractions.
AB  - We present a pilot study on the effects of milk protein fractions [alphaS1-casein
      (CN), alphaS2-CN, kappa-CN, beta-CN, and a mix of alpha-lactalbumin (alpha-LA)
      and beta-lactoglobulin (beta-LG)] from different animal species (bovine, ovine,
      and caprine) on pro- and anti-inflammatory cytokines and oxidative status in
      cultured peripheral blood mononuclear cells from children with generalized
      epilepsy. Peripheral blood mononuclear cells (PBMC) were obtained by density
      gradient from blood of 10 children with generalized epilepsy (5 males; mean age
      33.6 +/- 5.4 mo) and 10 controls (5 males; mean age 35.6 +/- 6.8 mo). Children
      with epilepsy were grouped according to cytokine levels as follows: children with
      epilepsy having low levels of cytokines not different from those of control
      children (LL-EC); children with epilepsy having cytokine levels at least 5-fold
      higher (medium levels) than those of control children (ML-EC); and children with
      epilepsy having cytokine levels at least 10-fold higher (high levels) than those
      of control children (HL-EC). The production of tumor necrosis factor-alpha (TNF
      alpha), IL-10, IL-6, and IL-1beta was studied in cultured PBMC incubated with
      alphaS1-CN, alphaS2-CN, kappa-CN, beta-CN, and a mix of alpha-LA and beta-LG from
      bovine, caprine, and ovine milks. The levels of reactive oxygen and nitrogen
      species (ROS/RNS) and catalase activity were assessed in cultured supernatant. In
      the HL-EC group, beta-CN from small ruminant species (ovine and caprine) induced
      the highest levels of TNF-alpha, whereas PBMC incubated with alphaS2-CN from
      ovine milk and the mix of beta-LG and alpha-LA from all tested milk species had
      the lowest levels of TNF-alpha. Within the HL-EC group, production of IL-1beta
      was higher for bovine and ovine alphaS2-CN fractions and lower for caprine and
      ovine beta-CN and kappa-CN. In the HL-EC group, IL-6 was higher in cultured PBMC
      incubated with alphaS2-CN from bovine and ovine milk than from caprine milk. The
      cytokine IL-10 did not differ among milking species. The highest levels of
      ROS/RNS were found after incubation of PBMC with the beta-CN fraction in bovine
      milk. Catalase activity was higher in PBMC cultured with beta-CN isolated from
      bovine and caprine milk and with alphaS1-CN from ovine milk.

PMID- 29573803
TI  - Comparison of effects of routine topical treatments in the milking parlor on
      digital dermatitis lesions.
AB  - Digital dermatitis (DD), an infectious bacterial disease affecting the feet of
      dairy cattle, can cause lameness and decrease milk production, fertility, and
      animal welfare. Current DD treatment typically involves routine hoof trimming and
      topical antibiotics. Several nonantibiotic commercial topical products are used
      for controlling DD lesions; however, there is limited or no evidence regarding
      their effectiveness. The objectives of this study were to evaluate 2 commercially
      available topical applications on their ability to (1) clinically cure active DD
      lesions to nonactive lesions and (2) prevent recurrence of active DD lesions. Ten
      farms were visited weekly. In the milking parlor, the hind feet of lactating
      cattle were cleaned and scored (M-stage scoring system). Cattle with DD lesions
      at the first visit were randomly allocated to 1 of 4 treatment groups: positive
      control (tetracycline solution), HealMax (AgroChem Inc., Saratoga Springs, NY),
      HoofSol (Diamond Hoof Care Ltd., Intracare BV, Veghel, the Netherlands), and a
      negative control (saline). All products were applied to lesions using a spray
      bottle. Tetracycline, HealMax, and HoofSol had a higher probability of clinical
      cure for active lesions compared with saline 1 wk after the first treatment (wk
      1), with 69, 52, and 79% clinical cure of active lesions, respectively, compared
      with 34% with saline. At wk 7, the probability of clinical cure for active
      lesions was 10, 33, 31, and 45% of lesions treated weekly with saline,
      tetracycline, HealMax, and HoofSol, respectively (no difference among
      treatments). The substantial clinical cure with saline highlighted the potential
      importance of cleaning feet. In wk 1, treatment with saline, tetracycline,
      HealMax, and HoofSol resulted in a probability of recurrence of active DD lesions
      of 9, 11, 11, and 8%, respectively, with no product being superior to saline.
      After 7 wk, the probability of recurrence of active lesions was 5, 7, 6, and 6%
      for saline, tetracycline, HealMax, and HoofSol respectively, with no difference
      among groups in wk 7. These results provide alternatives to antibiotics for
      treatment of DD lesions and highlight the potential importance of cleaning feet
      in the milking parlor.

PMID- 29573804
TI  - Effects of homolactic bacterial inoculant on the performance of lactating dairy
      cows.
AB  - The objective of this experiment was to determine the effect of applying a
      homofermentative bacterial inoculant to corn silage on the performance of dairy
      cows. After harvesting, corn forage was treated with nothing (CON) or with an
      inoculant containing a mixture of Lactococcus lactis, Lactobacillus plantarum,
      and Enterococcus faecium at 1.5 * 105 cfu/g of fresh forage (MC; SiloSolve MC,
      Chr. Hansen A/S, Horsholm, Denmark). After 186 d of storage in Ag-Bags (A Miller
      St. Nazianz Inc., St. Nazianz, WI), silages were fed as part of a total mixed
      ration containing 55% concentrates, 10% alfalfa hay, and 35% CON or MC corn
      silage. Sixty early-lactation Holstein dairy cows (30 multiparous and 30
      primiparous) housed in a freestall barn with Calan gates (American Calan Inc.,
      Northwood, NH) were assigned to the dietary treatments from 20 to 100 d in milk.
      Silage inoculated with MC had a more homofermentative pattern evidenced by
      greater lactic acid concentration (3.83 vs. 4.48% of DM) and lower concentrations
      of acetic (2.34 vs. 1.68% of DM) and propionic (0.37 vs. 0.10% of DM) acids and
      ammonia (9.11 vs. 7.82% of N) for CON and MC, respectively. Dry matter intake
      (23.1 vs. 23.2 kg/d) did not differ among treatments, but the MC silage had
      greater apparent digestibility of DM (68.8 vs. 70.8%), which led to greater
      yields of milk (37.7 vs. 38.5 kg/d), fat-corrected milk (37.6 vs. 38.4 kg/d),
      milk fat (1.30 vs. 1.33 kg/d), and lactose (1.83 vs. 1.92 kg/d) for CON and MC
      cows, respectively. Milk from cows fed MC silage had higher lactose (4.86 vs.
      4.93%), lower protein (2.93 vs. 2.83%), and similar contents of fat (3.47 vs.
      3.44%) compared with CON cows. Feed efficiency (fat-corrected milk/dry matter
      intake) was not affected by treatment (1.69 vs. 1.72 for CON and MC,
      respectively). Inoculation of corn silage with the homofermentative inoculant
      increased digestibility of the total mixed ration and increased milk yield by
      lactating dairy cows.

PMID- 29573805
TI  - Hunter versus CIE color measurement systems for analysis of milk-based beverages.
AB  - The objective of our work was to determine the differences in sensitivity of
      Hunter and International Commission on Illumination (CIE) methods at 2 different
      viewer angles (2 and 10 degrees ) for measurement of whiteness, red/green, and
      blue/yellow color of milk-based beverages over a range of composition. Sixty
      combinations of milk-based beverages were formulated (2 replicates) with a range
      of fat level from 0.2 to 2%, true protein level from 3 to 5%, and casein as a
      percent of true protein from 5 to 80% to provide a wide range of milk-based
      beverage color. In addition, commercial skim, 1 and 2% fat high-temperature,
      short-time pasteurized fluid milks were analyzed. All beverage formulations were
      HTST pasteurized and cooled to 4 degrees C before analysis. Color measurement
      viewer angle (2 vs. 10 degrees ) had very little effect on objective color
      measures of milk-based beverages with a wide range of composition for either the
      Hunter or CIE color measurement system. Temperature (4, 20, and 50 degrees C) of
      color measurement had a large effect on the results of color measurement in both
      the Hunter and CIE measurement systems. The effect of milk beverage temperature
      on color measurement results was the largest for skim milk and the least for 2%
      fat milk. This highlights the need for proper control of beverage serving
      temperature for sensory panel analysis of milk-based beverages with very low fat
      content and for control of milk temperature when doing objective color analysis
      for quality control in manufacture of milk-based beverages. The Hunter system of
      color measurement was more sensitive to differences in whiteness among milk-based
      beverages than the CIE system, whereas the CIE system was much more sensitive to
      differences in yellowness among milk-based beverages. There was little difference
      between the Hunter and CIE system in sensitivity to green/red color of milk-based
      beverages. In defining milk-based beverage product specifications for objective
      color measures for dairy product manufacturers, the viewer angle, color
      measurement system (CIE vs. Hunter), and sample measurement temperature should be
      specified along with type of illuminant.

PMID- 29573806
TI  - Differing genetic trend estimates from traditional and genomic evaluations of
      genotyped animals as evidence of preselection bias in US Holsteins.
AB  - The objective of this study was to compare genetic trends from single-step
      genomic BLUP (ssGBLUP) and traditional BLUP models for milk production traits of
      US Holsteins. Phenotypes were 305-d milk, fat, and protein yields from 21,527,040
      cows recorded between January 1990 and August 2015. The pedigree file included
      29,651,623 animals and was limited to 3 generations back from recorded or
      genotyped animals. Genotypes for 764,029 animals were used, and analyses were by
      a 3-trait repeatability model as used in the US official genetic evaluation.
      Unknown-parent groups were incorporated into the inverse of a relationship matrix
      (H-1 in ssGBLUP and A-1 in BLUP) with the QP transformation. For ssGBLUP, 18,359
      genotyped animals were randomly chosen as core animals to calculate the inverse
      of the genomic relationship matrix with the APY algorithm. Computations took 6.5
      h and 1.4 GB of memory for BLUP, and 13 h and 115 GB of memory for ssGBLUP. For
      genotyped sires with at least 10 daughters, the average genetic levels for
      predicted transmitting ability (PTA) and genomic PTA were similar up to 2008,
      with a higher level for ssGBLUP later (approximately by 36 kg for milk, 2.1 kg
      for fat, and 1.1 kg for protein for bulls born in 2010). For genotyped cows, the
      average genetic levels were similar up to 2006, with a higher level for ssGBLUP
      (approximately by 91 kg for milk, 3.6 kg for fat, and 2.7 kg for protein for cows
      born in 2012). For all cows, the average levels were slightly higher for ssGBLUP,
      with much smaller differences than for genotyped cows. Trends for BLUP indicate
      bias due to genomic preselection for genotyped sires and cows. For official
      evaluations released in December 2016, traditional PTA had the same trend as
      multiple-step genomic PTA for both genotyped bulls and cows except for the
      youngest bulls, who had traditional PTA slightly lower than genomic PTA. For
      genotyped bulls born in recent years, genetic gain for official traditional and
      genomic evaluations was similar in contrast to ssGBLUP and BLUP differences.
      Official PTA for cows were adjusted so that the Mendelian sampling variance was
      comparable with that for bulls, and those adjustments likely removed bias due to
      genomic preselection from traditional PTA, especially for genotyped cows. The
      ssGBLUP method seems to account partially for that bias and is computationally
      suitable for national evaluations.

PMID- 29573807
TI  - Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on
      gastrointestinal discomfort and symptoms in healthy adults: A double-blind,
      randomized, placebo-controlled study.
AB  - In a preliminary open-label trial by our group, Bifidobacterium bifidum YIT 10347
      (YIT10347) relieved gastric symptoms in patients with functional gastrointestinal
      disorders. Hence, in this study, we investigated the effects of YIT10347 on
      gastrointestinal symptoms in healthy adults. In this prospective double-blind,
      randomized, placebo-controlled trial (UMIN000024654), 100 healthy Japanese adults
      were randomly assigned to a YIT10347 group or placebo group and consumed 100 mL
      of YIT10347-fermented milk or placebo fermented milk, respectively, every day for
      4 wk. Gastrointestinal symptoms were evaluated by using the modified Frequency
      Scale for Symptoms of Gastroesophageal Reflux Disease (m-FSSG) and
      Gastrointestinal Symptom Rating Scale (GSRS) as primary endpoints. Mental
      symptoms, quality of life, salivary stress markers, and gastric emptying were
      evaluated as secondary endpoints. Effectiveness and safety were analyzed in a per
      protocol set (YIT10347 group, n = 39; placebo group, n = 40) and full analysis
      set (YIT10347 group, n = 50; placebo group, n = 50), respectively. In the m-FSSG
      evaluation, the YIT10347 group had a significantly higher relief rate of
      postprandial discomfort and greater changes in postprandial epigastric pain score
      from baseline than the placebo group. In the GSRS evaluation, the YIT10347 group
      had significantly higher relief rates of overall gastrointestinal symptoms, upper
      gastrointestinal symptoms, flatus, and diarrhea than the placebo group. We
      detected no significant differences in scores or relief rates of mental symptoms
      and quality of life, a salivary stress marker, or gastric emptying between the 2
      groups. No severe adverse events associated with test beverage consumption were
      observed in either group. These findings suggest that daily consumption of
      YIT10347-fermented milk exerts beneficial effects on gastrointestinal discomfort
      and symptoms such as postprandial discomfort and epigastric pain in healthy
      adults.

PMID- 29573808
TI  - Effect of temperature and pH on the properties of skim milk gels made from a
      tamarillo (Cyphomandra betacea) coagulant and rennet.
AB  - Reconstituted skim milk was gelled with a crude protease extract from tamarillo
      [Cyphomandra betacea or Solanum betacea (syn.)] fruit and compared with gels
      prepared with calf rennet. The effects of temperature and pH on the gelation of
      skim milk were investigated by small deformation oscillatory rheology. The
      tamarillo extract-induced gels had a faster rate of increase in the elastic
      modulus (G') at the early stage of gelation than rennet-induced milk gels. This
      was probably due to the broader proteolytic activity of tamarillo protease
      extracts as shown by sodium dodecyl sulfate-PAGE analysis. Confocal microscopy
      also showed that the milk gels resulting from the addition of tamarillo extracts
      had larger voids than rennet-induced milk gels. The proteolytic activity of
      tamarillo extracts was found to be optimal at pH 11. For both rennet and
      tamarillo extracts, the aggregation time was similar between pH 6.7 and 6.5, but
      the aggregation time of rennet-induced milk gels was lower than that of milk gels
      obtained by the addition of tamarillo extracts at pH lower than 6.5. An increase
      in temperature was found to have a significant effect on aggregation time,
      particularly at 20 degrees C, where rennet did not coagulate milk in 3 h but the
      tamarillo extracts coagulated milk within 2 h. The results of this study suggest
      that extracts from tamarillo fruit could be used for milk gelation, particularly
      under lower temperature or high pH conditions.

PMID- 29573809
TI  - [Development of a standardized guide for optimizing drug adherence information to
      be dispensed during a pharmaceutical counseling with a multiple myeloma patient:
      Initial validation].
AB  - The safety of the community treatment with oral anticancer therapies is a strong
      theme of the cancer plan 2014-2019. The objective of this study was to develop a
      Pharmaceutical Counseling Guide to improve medication adherence in patients
      treated for multiple myeloma with oral anticancer therapies. A multidisciplinary
      professional working group selected a list of relevant medication adherence
      related items that served as the framework for the design of the pharmaceutical
      counseling support materials in patient-accessible language. The readability,
      understanding and memorization of the information were validated in ten patients
      treated for myeloma. Twelve items were selected for treatment information (5
      items), treatment planning (5 items), and adverse drug effects (2 items). A
      pharmacist guide, a patient guide, a medication schedule, and three self
      questionnaires to evaluate medication knowledge and understanding of patients
      were developed. The patient test resulted in changes in these documents. This
      study carried out the initial validation of documents to standardize the
      pharmaceutical counseling for patients treated for myeloma so that it can be
      reproduced from one patient to another regardless of the pharmacist, by
      standardizing the information issued. This study needs to be completed by a final
      validation in myeloma patients, free from oral anticancer therapies.

PMID- 29573810
TI  - Meta-Analysis of Trials on Prophylactic Use of Levosimendan in Patients
      Undergoing Cardiac Surgery.
AB  - BACKGROUND: The role of prophylactic levosimendan in patients undergoing cardiac
      surgery is controversial. METHODS: We performed a computerized search of Medline,
      Embase, and Cochrane databases through September 2017 for randomized trials
      evaluating the prophylactic use of levosimendan in patients undergoing cardiac
      surgery (ie, patients without low cardiac output syndrome). The main study
      outcome was mortality at 30 days. RESULTS: The final analysis included 16
      randomized trials with total of 2,273 patients. There was no statistically
      significant difference in mortality at 30 days between levosimendan and control
      groups (relative risk 0.68, 95% confidence interval [CI]: 0.45 to 1.03). Subgroup
      analysis showed no statistically significant difference in mortality at 30 days
      for patients with reduced left ventricular ejection fraction compared with
      patients having preserved left ventricular ejection fraction (p for interaction =
      0.12). Further analysis suggested that levosimendan might be associated with
      improved mortality at 30 days when compared with active-control but not when
      compared with placebo (p for interaction = 0.01). The levosimendan group had a
      significant reduction in acute kidney injury (relative risk 0.59, 95% CI: 0.38 to
      0.92), intensive care unit stay (standardized mean difference = -0.21, 95% CI: 
      0.29 to -0.13), and ventilation time (standardized mean difference = -0.43, 95%
      CI: -0.61 to -0.25), whereas it had higher rates of atrial fibrillation (relative
      risk 1.11, 95% CI: 1.00 to 1.24). No statistically significant differences were
      observed between groups in mortality beyond 30 days, postoperative dialysis, or
      myocardial infarction. CONCLUSIONS: Prophylactic use of levosimendan does not
      appear to reduce the mortality at 30 days or beyond 30 days in patients
      undergoing cardiac surgery. This lack of benefit was noted irrespective of the
      LVEF.

PMID- 29573811
TI  - The discovery of deep-water seagrass meadows in a pristine Indian Ocean
      wilderness revealed by tracking green turtles.
AB  - Our understanding of global seagrass ecosystems comes largely from regions
      characterized by human impacts with limited data from habitats defined as
      notionally pristine. Seagrass assessments also largely focus on shallow-water
      coastal habitats with comparatively few studies on offshore deep-water
      seagrasses. We satellite tracked green turtles (Chelonia mydas), which are known
      to forage on seagrasses, to a remote, pristine deep-water environment in the
      Western Indian Ocean, the Great Chagos Bank, which lies in the heart of one of
      the world's largest marine protected areas (MPAs). Subsequently we used in-situ
      SCUBA and baited video surveys to survey the day-time sites occupied by turtles
      and discovered extensive monospecific seagrass meadows of Thalassodendron
      ciliatum. At three sites that extended over 128 km, mean seagrass cover was 74%
      (mean range 67-88% across the 3 sites at depths to 29 m. The mean species
      richness of fish in seagrass meadows was 11 species per site (mean range 8-14
      across the 3 sites). High fish abundance (e.g. Siganus sutor: mean MaxN.site-1 =
      38.0, SD = 53.7, n = 5) and large predatory shark (Carcharhinus amblyrhynchos)
      (mean MaxN.site-1 = 1.5, SD = 0.4, n = 5) were recorded at all sites. Such
      observations of seagrass meadows with large top predators, are limited in the
      literature. Given that the Great Chagos Bank extends over approximately 12,500
      km2 and many other large deep submerged banks exist across the world's oceans,
      our results suggest that deep-water seagrass may be far more abundant than
      previously suspected.

PMID- 29573812
TI  - Corrigendum to "Prognostic Impact of Interleukin-1 Receptor Antagonist in
      Patients with documented Coronary Artery Disease" [Int. J. Cardiol. 257 (2018) 24
      29].

PMID- 29573813
TI  - Appetite-associated responses to central neuropeptide Y injection in quail.
AB  - The appetite-associated effects of neuropeptide Y (NPY) have been extensively
      studied in mammalian models. Less knowledge exists for other vertebrate species
      including birds. The aim of this study was to determine the effects of central
      injection of NPY on feeding behavior and hypothalamic physiology in 7 day-old
      Japanese quail (Coturnix japonica). During the light cycle,
      intracerebroventricular injection of 1.9 pmol, 0.5, and 1.0 nmol doses of NPY did
      not affect food intake, 0.031 to 0.13 nmol increased food intake, and 2.0 nmol
      NPY decreased food intake, in comparison to vehicle injection. Multiple doses of
      NPY stimulated water intake, but when food was not available, water intake was
      not affected. When injected during the dark cycle, NPY did not influence food
      intake. NPY-injected chicks had more c-Fos immunoreactive cells in the arcuate
      nucleus of the hypothalamus (ARC) and greater hypothalamic agouti-related peptide
      and neuropeptide Y receptors 1 and 2 (NPYR1 and NPYR2, respectively) mRNA than
      vehicle-injected chicks. Within the ventromedial hypothalamus, NPY-treated chicks
      expressed less NPYR1 mRNA, within the dorsomedial hypothalamus less NPY mRNA, and
      in the ARC greater NPYR2 mRNA than vehicle-injected chicks. Lastly, quail
      injected with NPY increased feeding pecks, escape attempts, and time spent
      preening, while locomotion, the number of steps, and time spent perching
      decreased compared to chicks injected with the vehicle. Results demonstrate that
      NPY stimulates food intake in quail, consistent with mammals and other avian
      species, but with some unique responses at the molecular level that are not
      documented in other species.

PMID- 29573814
TI  - Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with
      Early-Stage Primary Open-Angle Glaucoma.
AB  - PURPOSE: To evaluate the ability of chromatic pupillometry to reveal abnormal
      pupillary responses to light in patients with early-stage primary open-angle
      glaucoma (POAG) and to test whether the degree of pupillometric impairment
      correlates with structural hallmarks of optic nerve damage in the disease.
      DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six patients with early-stage
      POAG (63.4+/-8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy
      controls (61.4+/-8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had
      a visual field mean deviation (VFMD) of -6 decibels or better on automated
      perimetry. METHODS: Each participant underwent a monocular 2-minute exposure to
      blue light (462 nm) followed by another 2-minute exposure to red light (638 nm)
      using a modified Ganzfeld dome equipped with a light-emitting diode lighting
      system. The light stimuli intensity was increased logarithmically to evaluate the
      combined extrinsic and intrinsic response of intrinsically photosensitive retinal
      ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were
      assessed monocularly using infrared pupillography. MAIN OUTCOME MEASURES:
      Baseline-adjusted, light-induced pupillary constriction amplitudes were
      calculated, and individual irradiance-response curves were constructed for each
      stimulus. Pupillary constriction amplitudes were compared between groups and
      across light intensities using a linear mixed model analysis. The linear
      relationship between pupillometric parameters and different structural and
      functional features of glaucoma was assessed using Pearson's correlation
      analysis. RESULTS: Light-induced pupillary constriction was reduced in patients
      with early-stage POAG compared with controls at moderate to high irradiances
      (>=11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal
      pupillary constriction amplitude was correlated with retinal nerve fiber layer
      thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002)
      in patients with POAG but not in controls. Conversely, pupillometric parameters
      were not correlated with visual field scores in patients with early-stage POAG.
      CONCLUSIONS: Patients with early-stage POAG exhibit reduced pupillary responses
      to moderate and high irradiances of blue and red lights. This wavelength
      independent functional alteration correlates with structural thinning of the RNFL
      and could be the consequence of dysfunction or loss of melanopsin expressing
      ipRGCs in the early stages of the disease.

PMID- 29573815
TI  - Safety of Lumbar Puncture Performed on Dual Antiplatelet Therapy.
AB  - Practice guidelines generally recommend delaying lumbar puncture (LP) in patients
      on dual antiplatelet therapy, with these recommendations often citing an
      increased risk of hemorrhagic complications, specifically the development of
      epidural hematomas. However, no data exist about the risks of performing an LP in
      the setting of dual antiplatelet therapy and conclusions are often based on data
      from spinal anesthesia literature. We reviewed the medical records of 100
      patients who underwent LP while taking dual antiplatelet therapy. We recorded the
      number of traumatic and bloody cerebrospinal fluid results as well as the
      presence of any complications occurring within 3 months of the procedure.
      Complications requiring imaging or hospitalization were considered serious. The
      most common complication was back pain, which was reported by 2 patients, only 1
      of which was ultimately found to be attributable to the procedure. No serious
      complications occurred. Cerebrospinal fluid analysis was consistent with a
      traumatic LP, defined as having at least 100 red blood cells per microliter, in
      8% of cases. Bloody LP, defined as having 1000 red blood cells per microliter,
      occurred in 4% of cases. The percentage of traumatic or bloody LPs was within the
      range reported previously for LPs performed in any setting. Although this is a
      small study and additional review is necessary, performing LPs in the setting of
      dual antiplatelet therapy may not pose an increased risk of serious
      complications.

PMID- 29573816
TI  - Diabetes mellitus prevalence in patients with takotsubo syndrome: the case of the
      brain-heart disconnect.
AB  - BACKGROUND: Hyperactive autonomic nervous system (ANS) is among the postulated
      pathophysiologic mechanisms of takotsubo syndrome (TTS). Diabetes mellitus (DM)
      with its associated ANS peripheral neuropathy could exert a "protective"
      influence for the emergence of TTS. METHODS: A patient-based meta-analysis of the
      data obtained from all patients presented individually was carried out, focusing
      on age, gender, and history of hypertension (HTN) and DM. RESULTS: The
      prevalences of HTN and DM for all 2,342 patients, aged 61.1 +/- 17.3, 85.1%
      female, were 37.4% and 9.5%, for patients >= 60 years old were 45.8% and 11.7%,
      and for patients >=65 years old were 48.2% and 12.3%, correspondingly. The
      prevalence of DM in patients with TTS is less than half of the world's and USA's
      elderly populations. CONCLUSIONS: Prevalence of DM in patients with TTS is lower
      than in the general population, suggesting that DM, may have a "protective"
      effect for the emergence of TTS.

PMID- 29573817
TI  - What Do You Think Makes a Good Undergraduate Laboratory Research Project?

PMID- 29573818
TI  - Understanding Alzheimer Disease at the Interface between Genetics and
      Transcriptomics.
AB  - Over 25 genes are known to affect the risk of developing Alzheimer disease (AD),
      the most common neurodegenerative dementia. However, mechanistic insights and
      improved disease management remains limited, due to difficulties in determining
      the functional consequences of genetic associations. Transcriptomics is
      increasingly being used to corroborate or enhance interpretation of genetic
      discoveries. These approaches, which include second and third generation
      sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific
      events connecting AD risk genes to expression profiles, and provide converging
      evidence of pathophysiological pathways underlying AD. Simultaneously, they
      highlight brain region- and cell-type-specific expression patterns, and
      alternative splicing events that affect the straightforward relation between a
      genetic variant and AD, re-emphasizing the need for an integrated approach of
      genetics and transcriptomics in understanding AD.

PMID- 29573819
TI  - Disease burden and challenges of chronic kidney disease in North and East Asia.

PMID- 29573820
TI  - Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with
      covalently linked small molecule imidazoquinoline TLR7/8 agonist.
AB  - Improving the immunogenicity of subunit vaccines, in particular skewing of the
      immune response towards Th1 type immunity, is crucial for the development of
      effective vaccines against intracellular infections and for the development of
      anti-cancer vaccines. Small molecule TLR7/8 agonist hold high potential for this
      purpose, but suffer from an undesirable pharmacokinetic profile, resulting in
      systemic inflammatory responses. An effective solution to this problem is
      covalent ligation to a larger carrier. Here, a degradable nanogel carrier
      containing a covalently linked imidazoquinoline (IMDQ) TLR7/8 agonist is explored
      as adjuvant for vaccination against the respiratory syncytial virus (RSV). In
      vitro and in vivo experiments in mice provide a solid rational base for
      preferring nanogels over soluble polymers as IMDQ carrier in terms of cellular
      uptake and lymph node accumulation.

PMID- 29573821
TI  - Wnt signaling and bone regeneration: Can't have one without the other.
AB  - Advances in the understanding of the complexities of the Wnt signaling pathway
      during development and tissue homeostasis have made the Wnt pathway one of the
      prime candidates for translational applications during tissue regeneration. Wnts
      are key components of the stem cell niche and are short range signaling molecules
      responsible for cellular decisions such as proliferation and differentiation.
      Systemic treatment using biologics targeting the Wnt signaling pathway have shown
      promising early results and will likely enter the clinical arena in the near
      future. This comprehensive review summarizes the intricacies how Wnts function in
      the context of the bone regeneration.

PMID- 29573822
TI  - Efficacy of soft coagulation in retroperitoneal lymphadenectomy for ovarian
      cancer.

PMID- 29573823
TI  - Determination of the proton RBE in the rat spinal cord: Is there an increase
      towards the end of the spread-out Bragg peak?
AB  - BACKGROUND AND PURPOSE: To determine the relative biological effectiveness (RBE)
      of protons in the rat spinal cord as a function of linear energy transfer (LET)
      and dose. MATERIALS AND METHODS: The rat cervical spinal cord was irradiated with
      single or two equal fractions (split doses) of protons at four positions (LET 1.4
      5.5 keV/um) along a 6 cm spread-out Bragg peak (SOBP). From dose-response
      analysis, TD50- (dose at 50% effect probability) and RBE-values were derived
      using the endpoint of radiation-induced myelopathy. RESULTS: Along the SOBP, the
      TD50-values decreased from 21.7 +/- 0.3 Gy to 19.5 +/- 0.5 Gy for single and from
      32.3 +/- 0.3 Gy to 27.9 +/- 0.5 Gy for split doses. The corresponding RBE-values
      increased from 1.13 +/- 0.04 to 1.26 +/- 0.05 (single doses) and from 1.06 +/-
      0.02 to 1.23 +/- 0.03 (split doses). CONCLUSIONS: For the relative high
      fractional doses, the experimental RBE at the distal edge of the proton SOBP is
      moderately increased. The conventionally applied RBE of 1.1 appears to be valid
      for the mid-SOBP region, but the higher values occurring more distally could be
      of clinical significance, especially if critical structures are located in this
      area. Further in vivo studies at lower fractional doses are urgently required.

PMID- 29573824
TI  - Heterogeneous MET gene copy number and EGFR mutation elicit discordant responses
      to crizotinib between primary and metastatic lesions in erlotinib-resistant lung
      adenocarcinoma.

PMID- 29573825
TI  - Inorganic fouling mitigation by salinity cycling in batch reverse osmosis.
AB  - Enhanced fouling resistance has been observed in recent variants of reverse
      osmosis (RO) desalination which use time-varying batch or semi-batch processes,
      such as closed-circuit RO (CCRO) and pulse flow RO (PFRO). However, the
      mechanisms of batch processes' fouling resistance are not well-understood, and
      models have not been developed for prediction of their fouling performance. Here,
      a framework for predicting reverse osmosis fouling is developed by comparing the
      fluid residence time in batch and continuous (conventional) reverse osmosis
      systems to the nucleation induction times for crystallization of sparingly
      soluble salts. This study considers the inorganic foulants calcium sulfate
      (gypsum), calcium carbonate (calcite), and silica, and the work predicts maximum
      recovery ratios for the treatment of typical water sources using batch reverse
      osmosis (BRO) and continuous reverse osmosis. The prediction method is validated
      through comparisons to the measured time delay for CaSO4 membrane scaling in a
      bench-scale, recirculating reverse osmosis unit. The maximum recovery ratio for
      each salt solution (CaCO3, CaSO4) is individually predicted as a function of
      inlet salinity, as shown in contour plots. Next, the maximum recovery ratios of
      batch and conventional RO are compared across several water sources, including
      seawater, brackish groundwater, and RO brine. Batch RO's shorter residence times,
      associated with cycling from low to high salinity during each batch, enable
      significantly higher recovery ratios and higher salinity than in continuous RO
      for all cases examined. Finally, representative brackish RO brine samples were
      analyzed to determine the maximum possible recovery with batch RO. Overall, the
      induction time modeling methodology provided here can be used to allow batch RO
      to operate at high salinity and high recovery, while controlling scaling. The
      results show that, in addition to its known energy efficiency improvement, batch
      RO has superior inorganic fouling resistance relative to conventional RO.

PMID- 29573826
TI  - Development of voluntary private health insurance in Nordic countries - An
      exploratory study on country-specific contextual factors.
AB  - The Nordic countries are healthcare systems with tax-based financing and
      ambitions for universal access to comprehensive services. This implies that
      distribution of healthcare resources should be based on individual needs, not on
      the ability to pay. Despite this ideological orientation, significant expansion
      in voluntary private health insurance (VPHI) contracts has occurred in recent
      decades. The development and role of VPHIs are different across the Nordic
      countries. Complementary VPHI plays a significant role in Denmark and in Finland.
      Supplementary VPHI is prominent in Norway and Sweden. The aim of this paper is to
      explore drivers behind the developments of the VPHI markets in the Nordic
      countries. We analyze the developments in terms of the following aspects: the
      performance of the statutory system (real or perceived), lack of coverage in
      certain areas of healthcare, governmental interventions or inability to reform
      the system, policy trends and the general socio-cultural environment, and policy
      responses to voting behavior or lobbying by certain interest groups. It seems
      that the early developments in VPHI markets have been an answer to the gaps in
      the national health systems created by institutional contexts, political
      decisions, and cultural interpretations on the functioning of the system.
      However, once the market is created it introduces new dynamics that have less to
      do with gaps and inflexibilities and more with cultural factors.

PMID- 29573827
TI  - The experience of being a psychiatric nurse in South Africa: A qualitative
      systematic review.
AB  - PURPOSE: The purpose of the study was to summarize the experiences of African
      psychiatric nurses in their workplace by examining the findings of existing
      qualitative studies. METHODS: Eleven studies published in English, Portuguese,
      and Spanish, between 1998 and 2016, which explored psychiatric nurses'
      experiences in Africa, were included. FINDINGS: After meta-aggregation, five key
      findings were identified: 1) organization and management, 2) perceptions of
      professional safety and insecurity, 3) relationship with the patient, 4)
      emotional experiences and 5) recommendations for improvement. DISCUSSION: The
      findings in this study highlight the stressful nature of the work climate of the
      psychiatric nurse in South Africa. More focus on improving working conditions and
      providing support is necessary to increase the quality of care for psychiatric
      mental health patients and their nurse providers.

PMID- 29573828
TI  - Systems biology for nursing in the era of big data and precision health.
AB  - BACKGROUND: The systems biology framework was previously synthesized with the
      person-environment-health-nursing metaparadigm. PURPOSE: The purpose of this
      paper is to present a nursing discipline-specific perspective of the association
      of systems biology with big data and precision health. METHOD: The fields of
      systems biology, big data, and precision health are now overviewed, from origins
      through expansions, with examples of what is being done by nurses in each area of
      science. DISCUSSION: Technological advances continue to expand omics and other
      varieties of big data that inform the person's phenotype and health outcomes for
      precision care. Meanwhile, millions of participants in the United States are
      being recruited for health-care research initiatives aimed at building the
      information commons of digital health data. CONCLUSIONS: Implications and
      opportunities abound via conceptualizing the integration of these fields through
      the nursing metaparadigm.

PMID- 29573829
TI  - Comparison of theory and experiment for NAPL dissolution in porous media.
AB  - Contamination of groundwater resources by an immiscible organic phase commonly
      called NAPL (Non Aqueous Phase Liquid) represents a major scientific challenge
      considering the residence time of such a pollutant. This contamination leads to
      the formation of NAPL blobs trapped in the soil and impact of this residual
      saturation cannot be ignored for correct predictions of the contaminant fate. In
      this paper, we present results of micromodel experiments on the dissolution of
      pure hydrocarbon phase (toluene). They were conducted for two values of the
      Peclet number. These experiments provide data for comparison and validation of a
      two-phase non-equilibrium theoretical model developed by Quintard and Whitaker
      (1994) using the volume averaging method. The model was directly upscaled from
      the averaged pore-scale mass balance equations. The effective properties of the
      macroscopic model were calculated over periodic unit cells designed from images
      of the experimental flow cell. Comparison of experimental and numerical results
      shows that the transport model predicts correctly - with no fitting parameters -
      the main mechanisms of NAPL mass transfer. The study highlights the crucial need
      of having a fair recovery of pore-scale characteristic lengths to predict the
      mass transfer coefficient with accuracy.

PMID- 29573830
TI  - Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and
      Concise Review of Literature.
AB  - Mucormycosis is an uncommonly encountered fungal infection in solid organ
      transplantation. The infection is severe and often results in a fatal outcome.
      The most common presentations are rhino-sino-orbital and pulmonary disease. We
      describe a rare case of gastric mucormycosis in a patient with a combined liver
      kidney transplant affected by glycogen storage disease type Ia. A 42-year-old
      female patient presented with gastric pain and melena 26 days after
      transplantation. Evaluation with upper endoscopy showed two bleeding gastric
      ulcers. Histological examination of gastric specimens revealed fungal hyphae with
      evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive
      therapy was reduced and antifungal therapy consisting of liposomal amphotericin B
      and posaconazole was promptly introduced. Gastrointestinal side effects of
      posaconazole and acute T-cell rejection of renal graft complicated management of
      the case. A prolonged course of daily injections of amphotericin B together with
      a slight increase of immunosuppression favored successful treatment of
      mucormycosis as well as of graft rejection. At 2-year follow-up, the woman was
      found to have maintained normal renal and liver function. We conclude that
      judicious personalization of antimicrobial and antirejection therapy should be
      considered to resolve every life-threatening case of mucormycosis in solid organ
      transplantation.

PMID- 29573831
TI  - Morphogenetic movements affect local tissue organisation during embryonic
      Drosophila morphogenesis.
AB  - Tissues and organs undergo extensive remodelling to reach their final morphology
      and physiological activity. The genetic programs underlying tissue formation are
      well studied, but less is known about how this formation is influenced by
      extrinsic forces derived from other concomitant morphogenetic events. Here we
      address this question in Drosophila melanogaster. We analyse tissue organisation
      in the embryonic epidermis at stage 10 by computational tissue segmentation
      methods to provide a quantitative description of packing. We find that the
      epidermis adopts different organisations along the dorso-ventral axis that
      correlate with differences in cell density. We analyse the contribution of three
      morphogenetic events that take place right before or concomitant to this period
      of embryogenesis, neuroblast delamination, asynchronous postblastoderm cell
      divisions and germ band extension, and we find that they all exert an influence
      on the packing of the epidermis. We previously described that the apical
      determinant Crumbs accumulates differentially in the epidermis along the dorso
      ventral axis. Here we find that this differential accumulation of Crumbs
      correlates with the differential tissue packing. Perturbation of the three
      mentioned morphogenetic events also modulate Crumbs differential accumulation,
      suggesting that Crb could act as a read-out of tissue organisation. We also
      previously showed that Crb plays a role in regulating cell architecture. Now we
      find that it is also required for proper packing of the embryonic epidermis. In
      summary, here we uncover an intimate relationship between morphogenetic events
      and cell packing within a tissue that is dependent on surrounding cell density.
      Furthermore we find that this morphogenetically-regulated tissue packing
      modulates the key cell polarity protein Crumbs, which in turn is required for
      tissue packing, suggesting that it may participate in the molecular mechanism/s
      underlying the described tissue organisation.

PMID- 29573832
TI  - Critical care nurses' knowledge of, adherence to, and barriers toward institution
      specific ventilator bundle.
AB  - BACKGROUND: Although evidence-based practices are known to improve the quality of
      care, making it cost-efficient and improving clinical results, barriers to
      transferring research into clinical practice have hindered this process. AIMS: To
      evaluate critical care nurses' knowledge of, adherence to, and barriers toward
      institution-specific ventilator bundle. MATERIAL AND METHODS: In 2015, we
      conducted an institution-specific, cross-sectional study in a 26-bed adult mixed
      medical-surgical intensive care unit (ICU) in Finland using quantitative survey
      of knowledge and self-reported adherence with qualitative gathering of barrier
      data. A pre-validated multiple-choice Ventilator Bundle Questionnaire was
      distributed to all registered nurses who were direct care providers (n = 155).
      RESULTS: The final response rate was 55.5% (n = 86), and 47.2% (n = 34) of
      respondents had more than 10 years of ICU experience. The levels of knowledge and
      self-reported adherence were 71.1% and 65.8% of the total score, respectively.
      The level of knowledge was higher among respondents who had received in-service
      education about ventilator bundle compared with respondents who had not received
      in-service education (27.0 vs 24.0 [P = .012]). Less experienced nurses reported
      significantly higher adherence than nurses with more ICU experience (29.0 vs 25.0
      [P = .034]). The correlation between knowledge and adherence scores was low (rho
      0.48 [P <.001]). The most well-known and adhered-to guidelines described patient
      positioning, daily chlorhexidine-based oral care, and strict hand hygiene. The
      least-known guidelines and those least adhered to described respiratory
      equipment, management of sedation and analgesia, and practices prior to and
      during endotracheal suctioning. The main barriers were related to the nurse
      respondents (e.g., lack of education [25.9%]), environment (e.g., role
      ambiguities [36.4%] and inadequate resources [21.1%]), and patients (e.g.,
      patient discomfort [4.8%] and fear of adverse effects [4.6%]). CONCLUSIONS: Self
      reported adherence did not correlate with knowledge and was not related to work
      experience. Most of the barriers toward evidence-based guidelines indicated a
      need for changes that are beyond the control of individual nurses.

PMID- 29573833
TI  - Erratum.

PMID- 29573834
TI  - Corrigendum to "Panaxynol, a natural Hsp90 inhibitor, effectively targets both
      lung cancer stem and non-stem cells" [Canc. Lett. 412 (2018) 297-307].

PMID- 29573835
TI  - High-intensity focused ultrasound therapy for the treatment of prostate cancer:
      Medium-term experience.
AB  - INTRODUCTION: The treatment of localised prostate cancer seeks to minimise the
      impact on sexual function and urinary continence. In this respect, therapy with
      high-intensity focused ultrasound offers important results. We present our
      experience with this technique in 2 Spanish centres. MATERIAL AND METHODS: We
      conducted a retrospective review of 75 patients with localised prostate cancer
      treated with high-intensity focused ultrasound between March 2007 and July 2016.
      The oncological results and perioperative complications were assessed, as well as
      the impact on sexual function and continence. RESULTS: A total of 67 patients
      were analysed. The mean follow-up was 7.2 years. The PSA nadir was 0.2ng/mL (0
      3), 24 patients (35.5%) presented biochemical recurrence, and 18 underwent a
      further biopsy, with 10 cases (55.5%) presenting disease recurrence. The overall
      biochemical relapse-free survival at 5 and 8 years was 93.2 and 80.5%,
      respectively. The cancer-specific survival at 5 and 8 years was 96% in both
      cases. In the postoperative period, 50 patients (74.6%) were continent, 16
      (23.9%) reported mild incontinence, and one (1.5%) reported moderate
      incontinence. The median International Index of Erectile Function-5 before and
      after the surgery was 17 (5-25) and 16 (2-23) points, respectively. Nine patients
      reported de novo erectile dysfunction (13.5%). CONCLUSION: High-intensity focused
      ultrasound appears to be a safe alternative for the treatment of localised
      prostate cancer, especially for low-risk localised prostate cancer. In our
      experience, this technique offers advantages in preserving urinary continence,
      and the medium-term oncological results are encouraging. Given the natural
      progression of prostate cancer, long-term studies with a larger number of cases
      are needed to corroborate these results.

PMID- 29573836
TI  - Choroidal metastasis of a minor salivary gland adenoid cystic carcinoma: A case
      report.
AB  - CASE REPORT: A 61-year-old man with a lower lip minor salivary gland adenoid
      cystic carcinoma, suffered from a unilateral progressive visual acuity loss due
      to choroidal metastasis. DISCUSSION: Adenoid cystic carcinoma is a rare primary
      tumour with significant metastatic potential. Our patient presented with a
      unilateral choroidal metastasis. According to the current literature, 8 cases of
      choroidal metastasis of salivary gland adenoid cystic carcinoma have been
      reported. This is the second case reported of choroidal metastasis with origin in
      a minor salivary gland, and the first one with origin in the minor salivary
      glands of the lower lip.

PMID- 29573837
TI  - Retinal toxicity due to canthaxanthin. Case series.
AB  - INTRODUCTION: Canthaxanthin is a chemical product used to tan the skin. Its most
      frequent adverse effect is canthaxanthin retinopathy. PURPOSE/ METHODS: Report,
      case series. RESULTS: Two female patients, one 42 years-old and the other 72
      years-old, with signs of retinopathy due to canthaxanthin. Complete ophthalmology
      examinations were carried out. The peripheral fovea birefringent deposits with
      internal retinal involvement were studied using multimodal imaging. CONCLUSION:
      Canthaxanthin retinopathy is rare. Multimodal imaging may provide important data
      for the differential diagnosis of crystalline retinopathy.

PMID- 29573838
TI  - Letter to the editor of "Current and future perspectives on the evaluation,
      prevention and conservative management of breast cancer related lymphoedema: A
      best practice guideline" from N. Gebruers and colleagues.

PMID- 29573839
TI  - Considerations on the effectiveness of educational strategies in outcomes related
      to workplace violence.

PMID- 29573840
TI  - Investigation of an outbreak of monkeypox in an area occupied by armed groups,
      Central African Republic.
AB  - BACKGROUND: Monkeypox is a zoonosis caused by an Orthopoxvirus of the Poxviridae
      family. Human infections are often severe and are a public health problem.
      PATIENTS AND METHOD: We conducted a monkeypox outbreak investigation of suspected
      case patients in five villages of the Alindao-Mingala Health District following
      blood sample confirmation of the virus by the Institut Pasteur in Bangui. We
      aimed to determine disease characteristics, to describe the context and the risk
      factors, and to measure the incidence and case fatality. Patients were reported
      in the villages of Rehou 4, 5, Dalakere 1, Kongbo, and Pavika from August to
      October 2016. Data was collected on individual records when interviewing patients
      or parents. RESULTS: A total of 26 patients were identified. The?10 years and 21
      30 years age groups were the most affected. The overall attack rate was 5 per
      1000 inhabitants and the case fatality was 7.7%. Young age and the absence of
      smallpox vaccination were associated with severe presentations in 87.5% of cases.
      CONCLUSION: The annual number of monkeypox outbreaks increases in the Central
      African Republic with severe presentations and a high case fatality especially in
      children. Reinforcing the surveillance and characterization of circulating
      strains will provide information on the need for vaccine production.

PMID- 29573841
TI  - Lack of effect of antibiotics on biopsy culture results in vertebral
      osteomyelitis.
AB  - We report a retrospective study of 173 patients with vertebral osteomyelitis
      evaluating the effect of antibiotics administered prior to percutaneous and open
      biopsy cultures. Antibiotics given prior to these biopsies did not have a
      significant effect on the yield of cultures.

PMID- 29573842
TI  - A case of severe Alexander disease with de novo c. 239 T > C, p.(F80S), in GFAP.
AB  - Alexander disease (AxD) is a progressive neurodegenerative disease caused by a
      mutation in the glial fibrillary acid protein (GFAP) gene. A 4-year-old boy
      presented several times with hemiclonic seizures with eye deviation for a few
      minutes at 28 days after birth. Electroencephalogram showed independent sharp
      waves in the right and left temporal area. Magnetic resonance imaging showed high
      intensity T1-weighted images in the white matter of the frontal lobe and basal
      ganglia. He showed no head control at 4 years of age, and his weight gain was
      insufficient. He did not show macrocephaly. At 4 years of age, he died of
      bacterial pneumonia and septic shock. He was diagnosed with AxD, and direct
      sequencing revealed a de novo known mutation, c. 239 T > C, p.(F80S), in GFAP.
      Hela and U2-OS cells transfected with GFAP cDNA with c. 239 T > C showed dot-like
      cytoplasmic aggregation, similar to R239C, a common mutation found in severe
      infantile AxD. Aggregation in the cytoplasm caused by a GFAP mutation is a
      hallmark of AxD. Although there is only one previous report of a patient with an
      F80S mutation, our data support that F80S can cause the severe, infantile form of
      AxD.

PMID- 29573843
TI  - Thoracic Imaging of Non-Small Cell Lung Cancer Treated With Anti-programmed Death
      Receptor-1 Therapy.
AB  - PURPOSE: Treatment with anti-programmed death receptor-1 (PD-1) therapeutics can
      lead to unconventional responses and side effect profiles due to their
      potentiating effects on the immune system. Here we evaluate the radiologic
      manifestations of anti-PD-1 therapy in the chest in patients with non-small cell
      lung cancer (NSCLC) receiving anti-PD-1 therapy. MATERIALS AND METHODS: A
      retrospective review of real-world clinical practice was conducted of all the
      patients with NSCLC receiving anti-PD-1 therapy at our institution between 2013
      and 2016. All patients without adequate clinical or radiologic follow-up data in
      the electronic medical records were excluded. Imaging examinations for all
      patients deemed by their thoracic oncologists to have radiologic
      pseudoprogression or therapy-associated pneumonitis were reviewed by experienced
      thoracic radiologists. RESULTS: A total of 166 patients with NSCLC had available
      clinical and imaging data for retrospective review. Of these patients, 4 (2%)
      were considered to have radiologic pseudoprogression, 3 of which manifested as
      increased tumor size and 1 of which manifested with new lesions. A total of 5
      patients (3%) were clinically deemed to have pneumonitis attributable to anti-PD
      1 therapy, 4 of which had radiologic manifestations on computed tomography.
      CONCLUSION: Radiologic pseudoprogression and drug-induced pneumonitis are
      uncommon but important manifestations of anti-PD-1 therapy on thoracic imaging.

PMID- 29573844
TI  - Expression of genes for enzymes synthesizing lysophosphatidic acid, its receptors
      and follicle developmental factors derived from the cumulus-oocyte complex is
      dependent on the ovarian follicle type in cows.
AB  - Cumulus-oocyte complexes (COCs) release factors potentially involved in
      follicular growth and development, such as growth and differentiation factor 9
      (GDF9), bone-morphogenetic protein 15 (BMP15), follistatin (FST) and cathepsins
      (CTSs). Moreover, the quality of the oocytes and follicles may be related to both
      the lipid composition of the follicle cells and follicular fluid. One of the
      lipids, locally regulating the reproductive functions in ovaries of cattle, is
      lysophosphatidic acid (LPA). In this study, the expression was investigated of
      the genes for LPA and other factors in COCs of follicles at different stages of
      development and regression. The relative abundances of mRNA were determined by
      real-time PCR for receptors for LPA (LPARs), enzymes synthesizing LPA (autotaxin
      (AX) and phospholipase A2 (PLA2)), BMP15, GDF9, CTSZ, CTSB and FST in COCs
      isolated from healthy, transitional and atretic follicles. The expression of
      genes for the LPARs, AX, PLA2 and the factors involved in follicular development
      in cattle COCs is follicle-type dependent. Greater expression of LPAR1-3 and AX
      genes were detected in the healthy follicles compared to the atretic and
      transitional follicles (P < 0.05). The relative abundance of GDF9, BMP15, CTSZ
      and CTSB was also greater in COCs from healthy follicles than from transitional
      and atretic follicles (P < 0.05). It is postulated that the greater expression of
      LPARs and AX genes in healthy follicles compared with atretic follicles indicates
      an enhanced role of LPA in follicular development. Results of the present study
      also suggest the regulatory role of factors derived from the COCs in the growth
      and development of follicles.

PMID- 29573845
TI  - Co-occurrence graphs for word sense disambiguation in the biomedical domain.
AB  - Word sense disambiguation is a key step for many natural language processing
      tasks (e.g. summarization, text classification, relation extraction) and presents
      a challenge to any system that aims to process documents from the biomedical
      domain. In this paper, we present a new graph-based unsupervised technique to
      address this problem. The knowledge base used in this work is a graph built with
      co-occurrence information from medical concepts found in scientific abstracts,
      and hence adapted to the specific domain. Unlike other unsupervised approaches
      based on static graphs such as UMLS, in this work the knowledge base takes the
      context of the ambiguous terms into account. Abstracts downloaded from PubMed are
      used for building the graph and disambiguation is performed using the
      personalized PageRank algorithm. Evaluation is carried out over two test datasets
      widely explored in the literature. Different parameters of the system are also
      evaluated to test robustness and scalability. Results show that the system is
      able to outperform state-of-the-art knowledge-based systems, obtaining more than
      10% of accuracy improvement in some cases, while only requiring minimal external
      resources.

PMID- 29573846
TI  - A Prospective Phase I/II Study of Docetaxel, Cisplatin and Continuous
      Capecitabine in Advanced Oesophago-Gastric Cancer (NWCOG-3).
AB  - AIMS: This open-label prospective phase I/II dose-escalation study determined the
      maximum tolerated dose (MTD) and then evaluated response, safety and feasibility
      of a novel combination of docetaxel, cisplatinum and capecitabine (DCC) in
      chemotherapy-naive patients with advanced oesophago-gastric carcinoma. MATERIALS
      AND METHODS: Patients with adenocarcinoma or squamous cell carcinoma of the
      oesophagus or stomach, of good performance status, deemed too advanced for
      curative treatment, were given systematically increasing doses of 3 weekly DCC to
      ascertain the MTD. Phase II administered up to six cycles of DCC at the MTD,
      assessing response and toxicity. RESULTS: Between November 2007 and November
      2012, 15 patients were recruited into phase I and 41 into phase II. The MDT was a
      21 day cycle of docetaxel 60 mg/m2 IV day 1, cisplatinum 60 mg/m2 IV day 1 and
      oral capecitabine 1000 mg/m2 daily in two divided doses for days 1-21. The most
      common phase II grade 3-4 toxicities were neutropenia 88% (10% febrile
      neutropenia), fatigue 15%, sensory neuropathy 10% and non-neutropenic infection
      10%. The overall response rate was 51%, median progression-free survival was 7.4
      months (confidence interval 6.7-9.4) and median overall survival was 10.9 months
      (confidence interval 7.7-13.7). CONCLUSION: DCC was tolerable and feasible with
      promising efficacy, and may be suitable for future investigation in both first
      line metastatic and neoadjuvant settings.

PMID- 29573848
TI  - Measurement properties of patient reported outcome measures for
      spondyloarthritis: A systematic review.
AB  - OBJECTIVES: This systematic review aimed to identify studies investigating
      measurement properties of patient reported outcome measures (PROMs) for
      spondyloarthritis (SpA), and to evaluate their methodological quality and level
      of evidence relating to the measurement properties of PROMs. METHODS: This
      systematic review was guided by the preferred reporting items for systematic
      review and meta-analysis (PRISMA). Articles published before 30 June 2017 were
      retrieved from PubMed(r), Embase(r), and PsychINFO(r) (Ovid). Methodological
      quality and level of evidence were evaluated according to recommendations from
      the COnsensus-based Standards for the selection of health Measurement INstruments
      (COSMIN). RESULTS: We identified 60 unique PROMs from 125 studies in 39
      countries. Twenty-one PROMs were validated for two or more SpA subtypes. The
      literature examined hypothesis testing (82.4%) most frequently followed by
      reliability (60.0%). A percentage of 77.7% and 42.7% of studies that assessed
      PROMs for hypothesis testing and reliability, respectively had "fair" or better
      methodological quality. Among the PROMs identified, 41.7% were studied in
      ankylosing spondylitis (AS) only and 23.3% were studied in psoriatic arthritis
      (PsA) only. The more extensively assessed PROMs included the ankylosing
      spondylitis quality of life (ASQoL) and bath ankylosing spondylitis functional
      index (BASFI) for ankylosing spondylitis, and the psoriatic arthritis quality of
      life questionnaire (VITACORA-19) for psoriatic arthritis. CONCLUSION: This study
      identified 60 unique PROMs through a systematic review and synthesized evidence
      of the measurement properties of the PROMs. There is a lack of validation of
      PROMs for use across SpA subtypes. Future studies may consider validating PROMs
      for use across different SpA subtypes.

PMID- 29573849
TI  - Dactylitis: A hallmark of psoriatic arthritis.
AB  - OBJECTIVE: Dactylitis-long considered a hallmark clinical feature of psoriatic
      arthritis (PsA)-occurs in 16-49% of patients with PsA. In this review, we discuss
      the pathology of dactylitis in PsA and clinical and imaging tools used to
      diagnose and monitor dactylitis. METHODS: PubMed literature searches were
      conducted using the terms psoriatic arthritis, dactylitis, pathology, imaging,
      ultrasound, magnetic resonance imaging, clinical, and indices. Articles were
      deemed relevant if they provided insight into the pathology, diagnosis, and/or
      monitoring of dactylitis in PsA, or if they discussed clinical or imaging indices
      used to assess dactylitis. RESULTS: Dactylitis in PsA often occurs
      asymmetrically, involves the feet more than the hands, and affects multiple
      digits simultaneously. Although dactylitis can be assessed clinically, imaging
      (radiography, ultrasound, magnetic resonance imaging, and bone scintigraphy) has
      provided key insights by documenting the various anatomic targets affected.
      Although inflammation can occur in most of the digital compartments, the nail has
      not been as well studied in dactylitic digits. Outcome measures for dactylitis
      range from dichotomous documentation to the Leeds dactylometer. Imaging outcome
      tools utilizing magnetic resonance imaging or ultrasound are under development.
      CONCLUSION: Dactylitis, which is associated with more erosive forms of PsA, is
      often the inaugural feature of PsA and may be the only feature for months to
      years. Early diagnosis and treatment of PsA favors better outcomes, possibly
      mitigating radiographic progression and destructive changes. Ultrasound and
      magnetic resonance imaging are useful tools that have not only shed light on the
      diverse tissues affected in dactylitis but can also be used to document ongoing
      inflammation. Ultrasound imaging dactylitis scores are being developed that will
      assist in diagnosing and documenting which compartments optimally respond to
      various treatment modalities.

PMID- 29573847
TI  - Granulocyte-macrophage colony-stimulating factor neuroprotective activities in
      Alzheimer's disease mice.
AB  - We investigated the effects of granulocyte-macrophage colony stimulating factor
      (GM-CSF) on behavioral and pathological outcomes in Alzheimer's disease (AD) and
      non-transgenic mice. GM-CSF treatment in AD mice reduced brain amyloidosis,
      increased plasma Abeta, and rescued cognitive impairment with increased
      hippocampal expression of calbindin and synaptophysin and increased levels of
      doublecortin-positive cells in the dentate gyrus. These data extend GM-CSF
      pleiotropic neuroprotection mechanisms in AD and include regulatory T cell
      mediated immunomodulation of microglial function, Abeta clearance, maintenance of
      synaptic integrity, and induction of neurogenesis. Together these data support
      further development of GM-CSF as a neuroprotective agent for AD.

PMID- 29573850
TI  - Clinical presentation of immune checkpoint inhibitor-induced inflammatory
      arthritis differs by immunotherapy regimen.
AB  - INTRODUCTION: Immune checkpoint inhibitors (ICIs) are a class of cancer
      immunotherapy, increasingly utilized to treat malignancies. Inflammatory
      arthritis (IA) is a potential consequence of ICI use, but there is limited
      information to guide evaluation and management of this immune-related adverse
      event (irAE). This study aimed to characterize clinical phenotypes, IA treatment
      and response in the largest cohort of patients with ICI-induced IA reported to
      date. METHODS: Patients with rheumatologist-confirmed IA occurring during or
      after ICI treatment with no prior history of autoimmune disease were included.
      Data were analyzed by ICI treatment regimen; treatments included combination CTLA
      4/PD-1 inhibition, anti-PD-1 or anti-PD-L1 monotherapy. Relationship to the
      development of other irAEs, management of IA, and outcomes of IA management were
      evaluated. RESULTS: Of 30 patients identified, those treated with combination ICI
      therapy were more likely to present with knee arthritis, to have higher levels of
      C-reactive protein, to have already had another irAE, and to have a reactive
      arthritis-like phenotype. In contrast, patients treated with ICI monotherapy were
      more likely to have initial small joint involvement and to have IA as their only
      irAE. Ten patients required additional immunosuppression beyond corticosteroids,
      with TNF-inhibitors and/or methotrexate. Tumor progression while on non
      corticosteroid immunosuppression was not seen in those with initial tumor
      response to ICIs. CONCLUSION: These data suggest that distinct IA phenotypes may
      emerge with exposure to different ICI regimens. The majority of patients referred
      to rheumatology required systemic immunosuppression to manage their IA symptoms.
      Tumor progression was not seen in patients requiring TNF-inhibitors.

PMID- 29573851
TI  - The Use of Multivitamin/Multimineral Supplements: A Modified Delphi Consensus
      Panel Report.
AB  - PURPOSE: Evidence supporting the use of dietary supplements, in particular,
      multivitamin/multimineral supplements (MVMS), has been mixed, complicating the
      ability of health care professionals to recommend their use. To clarify the role
      that MVMS can play in supporting human health, a series of consensus statements
      was developed based on expert opinion. METHODS: A panel of 14 international
      experts in nutritional science and health care was convened to develop consensus
      statements related to using MVMS in supporting optimal human health. The modified
      Delphi process included 2 rounds of remote voting and a final round of voting at
      a roundtable meeting where evidence summaries were presented and discussed. The
      level of agreement with each of 9 statements was rated on a 5-point Likert scale:
      agree strongly; agree with reservation; undecided; disagree; or disagree
      strongly. Consensus was predefined as >=80% of the panel agreeing strongly or
      agreeing with reservation to a given statement. FINDINGS: Consensus was reached
      for all statements. The panel determined that MVMS can broadly improve
      micronutrient intakes when they contain at least the micronutrients that are
      consumed insufficiently or have limited bioavailability within a specified
      population. MVMS formulations may also be individualized according to age, sex,
      life cycle, and/or other selected characteristics. There are specific biological
      processes and health outcomes associated with deficient, inadequate, and adequate
      micronutrient levels. Adequate intake is necessary for normal biological
      functioning required for good health; in some instances, higher than recommended
      micronutrient intakes have the potential to provide additional health benefits.
      Meeting daily intakes established by dietary reference values should be an
      explicit public health goal for individuals and populations. Use of MVMS is one
      approach to ensure that adequate micronutrient needs are met in support of
      biological functions necessary to maintain health. Long-term use of MVMS not
      exceeding the upper limit of recommended intakes has been determined to be safe
      in healthy adults. There is insufficient evidence to indicate that MVMS are
      effective for the primary prevention of chronic medical conditions, including
      cardiovascular disease and cancer. However, for certain otherwise healthy
      subpopulations (eg, pregnant women, older adults) and some individuals with
      existing medical conditions who experience inadequacies in micronutrient intake,
      addressing inadequacies by using MVMS can provide health benefits. IMPLICATIONS:
      This consensus panel has described key issues related to the use of MVMS among
      individuals at risk of or presenting with inadequacies in micronutrient intake or
      biomarker status.

PMID- 29573852
TI  - Benefits and Challenges of Lung Cancer Screening in Older Adults.
AB  - PURPOSE: Lung cancer screening with low-dose computed tomography has been shown
      to significantly reduce lung cancer-related mortality in high-risk patients.
      However, patients diagnosed with lung cancer are typically older and often have
      multiple age- and smoking-related comorbidities. As a result, cancer screening in
      older adults remains a complex decision, requiring careful consideration of
      patients' risk characteristics and life expectancy to ensure that the benefits
      outweigh the risks of screening. In this review, we evaluate the evidence
      regarding lung cancer screening, with a focus on older patients. METHODS: PubMed
      was searched to identify relevant studies evaluating the clinical outcomes of
      lung cancer screening. The key words used in our search included non-small cell
      lung cancer (NSCLC), screening, older, comorbidities, computed tomography, and
      survival. While we primarily looked for articles specific to older patients, we
      also focused on subgroup analysis in older patients in larger studies. Finally,
      we reviewed all relevant guidelines regarding lung cancer screening. FINDINGS:
      Guidelines recommend that lung cancer screening be considered in adults aged 55
      to 80 years who are at high risk based on smoking history (ie, 30-pack-year
      smoking history; having smoked within the past 15 years). Patients who fit these
      criteria have been shown to have a 20% reduction in lung cancer-related mortality
      with the use of low-dose computed tomography versus chest radiography. High rates
      of false-positive results and potential overdiagnoses were also observed.
      Therefore, screening is generally not recommended in adults with severe
      comorbidities or short life expectancy, who may experience limited benefit and
      higher risks with screening. However, several studies have shown a benefit with
      continued lung cancer screening with appropriate selection of older individuals
      at the highest risk and with the lowest comorbidities. IMPLICATIONS: Older
      patients experience the highest risk for lung cancer incidence and mortality, and
      stand to be the most likely to benefit from lung cancer screening. However,
      careful consideration must be given to higher rates of false-positives and
      overdiagnosis in this population, as well as tolerability of surgery and
      competing risks for death from other causes. The appropriate selection of older
      individuals for lung cancer screening can be greatly optimized by using validated
      risk-based targeting.

PMID- 29573853
TI  - Wildland firefighters and suicide risk: Examining the role of social
      disconnectedness.
AB  - Recent research has indicated that firefighters are at elevated suicide risk.
      Fire service organizations have called for research to examine fire service
      subgroups that might be at relatively increased suicide risk. Although anecdotal
      reports suggest that wildland firefighters represent one such group, to our
      knowledge, no study has empirically examined this conjecture. Thus, the present
      investigation examined if wildland firefighters report greater levels of suicide
      risk than non-wildland firefighters. Moreover, we sought to determine if two
      constructs proposed by the interpersonal theory of suicide to comprise suicidal
      desire-thwarted belongingness and perceived burdensomeness-statistically explain
      the link between wildland firefighter status and suicide risk. Merged data from
      two nationwide investigations of firefighter mental health were utilized (N =
      1,131; 68.2% male, 89.4% White). A total of 1.8% (n = 20) of the sample
      identified as wildland firefighters. Compared to non-wildland firefighters,
      wildland firefighters reported greater levels of suicide risk. Thwarted
      belongingness, but not perceived burdensomeness, statistically explained this
      link. Findings suggest that programs enhancing social connectedness within the
      fire service, particularly among wildland firefighters, might be one avenue for
      suicide prevention among firefighters. Results of this novel investigation should
      be interpreted in light of the relatively small subgroup of wildland
      firefighters.

PMID- 29573854
TI  - Nitric oxide involvement in additive antidepressant-like effect of agmatine and
      lithium in mice forced swim test.
AB  - Lithium is still the main agent in the management of mood disorders such as
      depression. Likewise, agmatine protects the central nervous system (CNS) against
      depression. The aim of the present study was to examine the possible additive
      antidepressant-like effect of agmatine and lithium in mice forced swim test (FST)
      as well as exploration of the probable involvement of nitric oxide (NO) pathway
      in this response. Results showed that pretreatment with a subeffective dose of
      agmatine (0.01 mg/kg) augmented the antidepressant-like effect of lithium
      subeffective dose (3 mg/kg) (P < 0.001). L-NG-nitroarginine methyl ester (L-NAME,
      nonspecific nitric oxide synthase [NOS] inhibitor) at doses of 10 and 30 mg/kg,
      and 7-nitroindazole (7-NI, neuronal NOS inhibitor) at doses of 15 and 30 mg/kg
      potentiated the antidepressant-like effect of the subeffective combination of
      lithium (3 mg/kg) and agmatine (0.001 mg/kg) (P < 0.001, P < 0.01, respectively).
      However, various doses of aminoguanidine (25 and 50 mg/kg, inducible NOS
      inhibitor) failed to alter the immobility time of the same combination (P >
      0.05). Moreover, pretreatment with subeffective doses of L-arginine (substrate
      for NOS, 300 and 750 mg/kg) reversed the augmenting antidepressant-like effect of
      agmatine (0.01 mg/kg) on lithium (3 mg/kg) (P < 0.001). Our results revealed that
      agmatine enhances the antidepressant-like effects of lithium and the NO pathway
      might mediate this phenomenon. In addition, constitutive NOS plays a dramatic
      role in this response.

PMID- 29573855
TI  - Sleep at night and association to aggressive behaviour; Patients in a Psychiatric
      Intensive Care Unit.
AB  - Evaluations of associations between sleep at night and aggressive behaviour in
      Psychiatric Intensive Care Units (PICU) are lacking. The aims were to explore if
      sleep duration or night-to-night variations in sleep duration correlated with
      aggressive behaviour and aggressive incidents the next day and through the whole
      admission. Fifty consecutive patients admitted to a PICU were included (521
      nights) and the nurses registered the time patients were sleeping, aggressive
      behaviour with The Broset Violence Checklist (BVC) and aggressive incidents with
      The Staff Observation Aggression Scale-Revised (SOAS-R). At admission, short
      sleep duration the first night correlated with aggressive behaviour the next day
      and admissions with violent incidents had a median of 4.0 h difference in sleep
      from night one to night two compared to 2.1 h for the rest of the admissions.
      During the stay, large absolute difference in sleep duration between two nights
      correlated with aggressive behaviour the next day and short sleep duration was
      associated with violent incidents. Short sleep duration and night-to-night
      variations in sleep duration are both associated with increased risk for
      aggression in PICUs. This observation might help to predict and prevent
      aggressive incidents.

PMID- 29573856
TI  - [Scleral abnormalities in high myopic posterior staphyloma on swept-source ocular
      coherence tomography].

PMID- 29573857
TI  - [Oculoplastic complications of the excision of meningiomas with orbital
      extension].
AB  - INTRODUCTION: Meningiomas with orbital extension are the most frequent benign
      orbital tumors. The few studies available on the postoperative complications of
      their excision focus on the postoperative evolution of proptosis, visual acuity
      and visual field deficits. The goal of our study was to highlight the
      oculoplastic complications secondary to their excision. MATERIAL AND METHOD: We
      identified all cases of meningiomas with orbital extension undergoing excision
      either neurosurgically or via an orbital approach in the ophthalmology and
      neurosurgery departments of Pasteur university medical center in Nice between
      February 2011 and January 2017. The data collection included the postoperative
      presence of proptosis, oculomotor disturbance, lid disorders, dry eye and
      trigeminal nerve damage. RESULTS: Twenty-nine patients were included; 89.7 % were
      women. The mean age was 55 years. Postoperative complications included 25 %
      residual proptosis; 40.7 % oculomotor disturbance, 75 % of which regressed at
      least partially; 50 % ptosis, 21 % of which did not regress; 40 % dry eye; and in
      21.4 % the trigeminal nerve was involved. CONCLUSION: The management of
      meningiomas with orbital extension is difficult due to their anatomical location
      and requires joint neurosurgical and oculoplastic management. Sufficient follow
      up is required before recommending surgery for oculomotor disturbances. The
      frequency of occurrence of ptosis with potential recommendation for surgery
      requires caution given the occurrence of trigeminal nerve involvement and dry eye
      syndrome.

PMID- 29573858
TI  - [Evaluation of the quality of life of patients fitted with scleral lenses using a
      Moroccan version of NEI-VFQ 25].
AB  - PURPOSE: To evaluate the contribution of scleral lenses in terms of improving
      quality of life and vision. METHODS: We conducted a retrospective study of the
      quality of life (QOL) of patients fitted with scleral lenses, between November
      2015 and November 2016 in the Marrakech university hospital department of
      ophthalmology. QOL was assessed before and after scleral lens (ICD) adaptation
      using a version of the National Eye Institute Visual Function Questionnaire 25
      translated into the Moroccan dialect of Arabic. RESULTS: We included 48 patients
      (68 eyes). The main indications included severe corneal ectasia followed by post
      keratoplasty eyes, post-traumatic corneas and patients with ocular surface
      disease. The average duration of scleral lens wear was 6 months, and the average
      wearing time was 12hours per day. BCVA increased from 0.8 to 0.2+/-0.5 LOGMAR.
      The average scores on the NEI-VFQ 25 of patients after scleral lens fitting were
      significantly higher, 80.5 versus 42.6 before wearing scleral lenses, thus an
      increase of 38.1. DISCUSSION: Quality of life has become a major issue in the
      healthcare field, which has seen a renewed interest in ophthalmology lately. The
      results of our study support the data from previous studies regarding the impact
      of scleral lenses on the quality of life of patients. CONCLUSION: High oxygen
      permeability scleral lenses are a satisfying therapeutic alternative, allowing a
      significant improvement in the quality of life of patients for whom the usual
      therapeutic means are limited.

PMID- 29573859
TI  - [Persistent pupillary membrane].

PMID- 29573860
TI  - ?
AB  - New anticancer therapies, immune pathway inhibitors, may cause immune-related
      adverse events (IRAE). Immune-related ocular toxicities are rare but are
      potentially serious adverse events. The purpose of this article is to report a
      case of ocular inflammatory involvement potentially related to the immune
      response and the use of nivolumab, a new immunologic agent used for the treatment
      of a solid tumor. Despite the implication of this therapy in the occurrence of
      inflammation, other causes must always be ruled out. It is possible to continue
      this therapy in consideration of the risk/benefit ratio for each patient. Close
      collaboration between oncologists and ophthalmologists is necessary in the
      diagnosis and timely management of IRAE related to these new emerging therapies.

PMID- 29573861
TI  - [Ocular toxocariasis].

PMID- 29573862
TI  - [Ocular surface aging: Pathophysiology and consequences for management].
AB  - All the components of the ocular surface and the lacrimal system are affected by
      aging. Aging induces lacrimal gland fibrosis, Meibomian gland dysfunction, loss
      of corneal sensitivity, decreased corneal cell density, impairment of immune
      defences, increased local inflammation associated with hormonal changes,
      conjunctivochalasis, lid abnormalities, etc. Furthermore, homeostasis of the
      ocular surface may be altered by various age-related systemic comorbidities and
      iatrogenic interventions. Altogether, aging is considered the most predominant
      risk factor for dry eye disease. The increasing knowledge of the pathophysiology
      of aging of the ocular surface allows for refinement of the management of ocular
      surface disease in the elderly.

PMID- 29573863
TI  - [Comparison of objective optical quality measured by double-pass aberrometry in
      patients with moderate dry eye: Normal saline vs. artificial tears: A pilot
      study].
AB  - Dry eye is defined by a tear film instability resulting in variable but
      systematic fluctuations in the quality of vision. Variability in optical quality
      can be demonstrated using a double pass aberrometer such as the OQAS (Optical
      Quality Analyzing System, Visiometrics). The goal of this work is to compare
      fluctuations in objective quality of vision measured by OQAS between treatment
      with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic
      acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye
      syndrome. Optical quality was measured by evaluating the variations in the
      Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria
      were dry eye syndrome with an Ocular Surface Disease Index (OSDI) score>23
      treated only with artificial tears. The patients were their own controls: OF in
      one eye and normal saline in the fellow eye. The choice of the subject eye and
      control eye was determined in a randomized fashion. OSI variations were measured
      in each eye before instillation, 5minutes and 2hours after instillation. The
      primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary
      endpoints were the number of blinks and patient's preference (preferred eye).
      Preliminary results were obtained on 19 patients. Average OSDI score was 36.8.
      Visual acuity was 10/10 with no significant difference between the two eyes.
      Prior to instillation, there was no significant difference between "normal
      saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In
      the normal saline eye, there was no significant variation in mean OSI, OSI
      variability, OSI slope, or number of blinks. However, in the "OF" eye, there was
      a significant variation between initial and 2-hour OSI variability (0.363 versus
      0.204; P<0.05), the average slope of OSI (0.04 versus 0.01; P<0.05) and the
      number of blinks (4.2 versus 2.8; P<0.05). Sixty-five percent of patients
      preferred the OF eye, 24% did not have a preference, and 11% preferred the normal
      saline eye. Objective quality of vision measured by OQAS is an interesting
      parameter for evaluating the effectiveness of a lacrimal substitute. The purpose
      of artificial tears is, among other things, to provide comfort and a reduction of
      dry eye symptoms such as poor quality of vision. This study demonstrates that
      0.5% carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear
      film and thus a significant improvement in the quality of vision compared to
      normal saline.

PMID- 29573864
TI  - Minimally invasive distal linear metatarsal osteotomy combined with selective
      release of lateral soft tissue for severe hallux valgus.
AB  - BACKGROUND: Minimally invasive techniques for hallux valgus have been widely used
      to treat mild to moderate hallux valgus deformities. The purpose of this study
      was to evaluate the clinical and radiographic outcomes of distal linear
      metatarsal osteotomy (DLMO), which is one of the minimally invasive techniques,
      for severe hallux valgus. METHODS: 95 patients (141 feet) with severe hallux
      valgus underwent DLMOs. Lateral soft tissue release (LSTR) was performed at the
      same time for the cases selected by an original manual test. The satisfaction
      level, the Japanese Society of Surgery of the Foot (JSSF) hallux scale score, and
      weight-bearing radiographs of the foot were assessed preoperatively and after
      more than 24 months. In addition, the clinical and radiographic outcomes were
      compared among three groups divided by the kind of LSTR: no LSTR; manual
      correction; and open release through skin incision. RESULTS: Although the first
      metatarsal bone was significantly shortened, dorsiflexed, and elevated on
      postoperative radiographs, the rate of satisfaction was 87.2% (123/141), and the
      mean JSSF hallux scale score improved significantly from 60.4 (44-73) to 90.4 (65
      100). The mean hallux valgus and intermetatarsal angles also improved
      significantly from 45.5 degrees  (40.0-60.0 degrees ) to 10.3 degrees  (-28.0
      40.9 degrees ) and from 19.9 degrees  (14.0-28.7 degrees ) to 8.3 degrees  (-1.6
      18.5 degrees ), respectively. Delayed union (18 feet), metatarsalgia (16 feet),
      recurrence (22 feet), and hallux varus (22 feet) were observed, and they were
      more obvious in DLMO combined with open release through a skin incision.
      CONCLUSIONS: DLMO combined selectively with LSTR is an effective procedure for
      correcting severe hallux valgus. However, the indication for open release with
      DLMO should be considered carefully.

PMID- 29573865
TI  - Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively
      associated with poorer prognosis.
AB  - BACKGROUND: The present study examined the clinical significance of metastasis
      associated protein 1 (MTA1) in the progression and patient survival of gastric
      cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n =
      436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for
      MTA1 protein, and scored according to the percentage of cells positively stained
      for MTA1 combined with stain intensity. Associations between MTA1 staining scores
      and clinicopathological factors, including survival time, were evaluated.
      RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer
      tissues than in matched normal tissues. MTA1 scores positively correlated with
      tumor size, depth of invasion, presence of lymph node metastasis, lymphatic
      involvement, venous invasion, distal metastasis, and advanced clinical staging.
      Patients with high MTA1 scores in gastric cancer tissues had a significantly
      lower five-year survival rate compared with patients with low MTA1 scores. The
      multivariate analysis indicated that MTA1 protein levels in resected gastric
      cancer tissues, as reflected by immunohistochemical staining, are an independent
      prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1
      immunopositivity was significantly associated with progression of gastric cancer,
      and may be helpful in gastric cancer prognosis.

PMID- 29573866
TI  - Expressional analysis of APLNR, an essential gene for cancer immunotherapy, in
      colon and prostate cancers.

PMID- 29573867
TI  - Brain-derived neurotrophic factor induces angiogenin secretion and nuclear
      translocation in human umbilical vein endothelial cells.
AB  - Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that
      induces growth of neurons. Recent studies have suggested that BDNF could act as
      an angiogenesis inducer similar to vascular endothelial growth factor (VEGF).
      Angiogenin is a strong mediator of angiogenesis. It has particular
      characteristics both as a secreted protein and a transcription factor. After
      being incorporated into the cytoplasm, angiogenin is immediately transferred to
      the nucleus and then mediates the angiogenic effects of angiogenesis inducers,
      including VEGF. The aim of this study is to determine the association between
      BDNF and angiogenin. At first, we determined the secretion of angiogenin from
      human umbilical vein endothelial cells (HUVEC) induced by BDNF with enzyme-linked
      immunosorbent assay. Next, we determined BDNF-induced nuclear translocation of
      angiogenin by immunofluorescent staining. In addition, we examined the mRNA
      expression of angiogenin in HUVEC before and after BDNF stimulation by
      quantitative reverse transcriptase-polymerase chain reaction. As a result, we
      noted that BDNF induced angiogenin secretion and nuclear translocation without an
      increase in the mRNA expression in HUVEC. Furthermore, we demonstrated that BDNF
      induced HUVEC proliferation was significantly suppressed when neomycin, a
      specific inhibitor of nuclear translocation of angiogenin, was administered.
      These findings indicate that nuclear translocation of angiogenin is critically
      involved in BDNF-induced proliferation of HUVEC. In conclusion, angiogenin
      contributes to angiogenesis induced by BDNF.

PMID- 29573868
TI  - Leo Martinez: striving to end childhood tuberculosis.

PMID- 29573869
TI  - Low back pain: a major global challenge.

PMID- 29573870
TI  - What low back pain is and why we need to pay attention.
AB  - Low back pain is a very common symptom. It occurs in high-income, middle-income,
      and low-income countries and all age groups from children to the elderly
      population. Globally, years lived with disability caused by low back pain
      increased by 54% between 1990 and 2015, mainly because of population increase and
      ageing, with the biggest increase seen in low-income and middle-income countries.
      Low back pain is now the leading cause of disability worldwide. For nearly all
      people with low back pain, it is not possible to identify a specific nociceptive
      cause. Only a small proportion of people have a well understood pathological
      cause-eg, a vertebral fracture, malignancy, or infection. People with physically
      demanding jobs, physical and mental comorbidities, smokers, and obese individuals
      are at greatest risk of reporting low back pain. Disabling low back pain is over
      represented among people with low socioeconomic status. Most people with new
      episodes of low back pain recover quickly; however, recurrence is common and in a
      small proportion of people, low back pain becomes persistent and disabling.
      Initial high pain intensity, psychological distress, and accompanying pain at
      multiple body sites increases the risk of persistent disabling low back pain.
      Increasing evidence shows that central pain-modulating mechanisms and pain
      cognitions have important roles in the development of persistent disabling low
      back pain. Cost, health-care use, and disability from low back pain vary
      substantially between countries and are influenced by local culture and social
      systems, as well as by beliefs about cause and effect. Disability and costs
      attributed to low back pain are projected to increase in coming decades, in
      particular in low-income and middle-income countries, where health and other
      systems are often fragile and not equipped to cope with this growing burden.
      Intensified research efforts and global initiatives are clearly needed to address
      the burden of low back pain as a public health problem.

PMID- 29573871
TI  - Low back pain: a call for action.
AB  - Low back pain is the leading worldwide cause of years lost to disability and its
      burden is growing alongside the increasing and ageing population.1 Because these
      population shifts are more rapid in low-income and middle-income countries, where
      adequate resources to address the problem might not exist, the effects will
      probably be more extreme in these regions. Most low back pain is unrelated to
      specific identifiable spinal abnormalities, and our Viewpoint, the third paper in
      this Lancet Series,2,3 is a call for action on this global problem of low back
      pain.

PMID- 29573873
TI  - CT-based Morphometric Analysis of Professional Opera Singers' Vocal Folds.
AB  - PURPOSE AND STUDY DESIGN: Our work aimed to study the relationship between the
      length of vocal folds and classical voice type among professional opera singers.
      Also, the present paper attempts to assess if individual features such as height
      and body mass index are associated with the vocal folds length (VFL) and the
      vocal range. Our research compared VFL and voice type by evaluation of neck
      computed tomography imaging of professional opera singers obtained between 2009
      and 2015. Vocal range was measured after scanning procedure by a speech-language
      pathologist. The results were used to compare VFL with vocal range, voice type,
      and individual features of every singer. MATERIAL AND METHODS: The group included
      93 opera singers (female: 31 sopranos, 15 mezzos, and 5 contraltos; male: 17
      tenors, 16 baritones, 6 basses, and 3 countertenors). Different values such as
      VFL, vocal range, and individuals' features (height, weight, body mass index)
      were analyzed statistically. RESULTS: Some significant differences and
      correlation were found. The VFL was diversified between classical voice types.
      VFL for soprano, mezzo-soprano, and bass was significantly different from every
      other type of voice. The vocal range has been shown to have a negative
      correlation with VFL value, which reflects the narrowest vocal range among bass
      voices. The analysis confirmed a linear correlation between VFL and individual
      features of the body such as height and body mass index. CONCLUSION: Presented
      data support the hypothesis that there are significant differences of VFL, vocal
      range, and body morphology between professional singers of different voice
      classification.

PMID- 29573872
TI  - Prevention and treatment of low back pain: evidence, challenges, and promising
      directions.
AB  - Many clinical practice guidelines recommend similar approaches for the assessment
      and management of low back pain. Recommendations include use of a biopsychosocial
      framework to guide management with initial non-pharmacological treatment,
      including education that supports self-management and resumption of normal
      activities and exercise, and psychological programmes for those with persistent
      symptoms. Guidelines recommend prudent use of medication, imaging, and surgery.
      The recommendations are based on trials almost exclusively from high-income
      countries, focused mainly on treatments rather than on prevention, with limited
      data for cost-effectiveness. However, globally, gaps between evidence and
      practice exist, with limited use of recommended first-line treatments and
      inappropriately high use of imaging, rest, opioids, spinal injections, and
      surgery. Doing more of the same will not reduce back-related disability or its
      long-term consequences. The advances with the greatest potential are arguably
      those that align practice with the evidence, reduce the focus on spinal
      abnormalities, and ensure promotion of activity and function, including work
      participation. We have identified effective, promising, or emerging solutions
      that could offer new directions, but that need greater attention and further
      research to determine if they are appropriate for large-scale implementation.
      These potential solutions include focused strategies to implement best practice,
      the redesign of clinical pathways, integrated health and occupational
      interventions to reduce work disability, changes in compensation and disability
      claims policies, and public health and prevention strategies.

PMID- 29573874
TI  - A multi-country study of dengue vaccination strategies with Dengvaxia and a
      future vaccine candidate in three dengue-endemic countries: Vietnam, Thailand,
      and Colombia.
AB  - BACKGROUND: The dengue vaccination era began when Dengvaxia (CYD-TDV) became
      available in 2016. In addition, several second-generation vaccine candidates are
      currently in phase 3 trials, suggesting that a broader availability of dengue
      vaccines may be possible in the near future. Advancing on the recent WHO-SAGE
      recommendations for the safe and effective use of CYD-TDV at the regional level
      on average, this study investigates the vaccination impacts and cost
      effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a
      country-specific manner for three endemic countries: Vietnam, Thailand, and
      Colombia. METHODS: The vaccination impacts of CYD-TDV and NVC were derived by
      fitting the empirical seroprevalence rates of 9 year olds into an individual
      based meta-population transmission model, previously used for the WHO-SAGE
      working group. The disability-adjusted life years were estimated by applying
      country-specific parametric values. The cost-effectiveness analyses of four
      intervention strategies in combination with routine and catch-up campaigns were
      compared for both vaccines to inform decision makers regarding the most suitable
      immunization program in each of the three countries. RESULTS AND CONCLUSION: Both
      CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000
      depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine
      vaccination programs and 10-29 year olds as a one-off catch-up campaign was the
      most cost-effective strategy in all three countries. With NVC, while the most
      cost-effective strategy was to vaccinate 9-29 and 9-18 year olds in Vietnam and
      Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old
      in Colombia was more cost-effective than other strategies. Given that three
      countries will soon face decisions regarding whether and how to incorporate CYD
      TDV or future dengue vaccines into their budget-constrained national immunization
      programs, the current study outcomes can be used to help decision makers
      understand the expected impacts and cost-effectiveness of such vaccines.

PMID- 29573875
TI  - Immunotherapeutic potential of Leishmania (Leishmania) donovani Th1 stimulatory
      proteins against experimental visceral leishmaniasis.
AB  - An effective therapeutic vaccination strategy is required for controlling
      visceral leishmaniasis (VL), a fatal systemic disease, through boosting the
      immunosuppressed state in Leishmania-infected individuals, as the majority of
      them living in the endemic regions exhibit either subclinical or asymptomatic
      infection which further often develops into a full-blown disease. Previously in
      our laboratory, several Th1 stimulatory recombinant proteins were successfully
      cloned, purified and assessed for their prophylactic efficacy against Leishmania
      challenge. Due to their immunostimulatory property, these proteins are needed to
      be evaluated for their immunotherapeutic potential in Leishmania-infected
      hamsters. Four proteins namely, aldolase, enolase, p45 and triose phosphate
      isomerase were taken up to immunize animals at different doses (50, 25 and 12.5
      MUg/animal). Immunization with lower doses of aldolase and enolase, i.e., 25 and
      12.5 MUg showed a significant decline (~60%) in parasitic load along with an
      enhanced cellular immune response. These findings indicate that vaccination with
      above -stated Th1 stimulatory proteins is an effective immunotherapeutic approach
      against experimental VL. However, their efficacies may further be improved in
      combination with known therapeutic regimens or immunomodulators.

PMID- 29573876
TI  - Humoral immunity 10 years after booster immunization with an adolescent and adult
      formulation combined tetanus, diphtheria, and 5-component acellular pertussis
      vaccine in the USA.
AB  - BACKGROUND: In a prospective, randomized pivotal phase III clinical trial, the
      immunogenicity and reactogenicity of a tetanus-diphtheria-acellular pertussis
      vaccine (Tdap) and a tetanus-diphtheria vaccine (Td) vaccine were studied in
      participants aged 11-64 years. Here we report antibody persistence through 10
      years after vaccination. METHODS: Participants who received Tdap or Td in the
      original phase III trial and provided pre- and post-vaccination serum samples
      were recruited to donate sera at 1, 3, 5 and 10 years post-vaccination. Antibody
      concentrations were measured using standard assay techniques. RESULTS: Initially,
      1457 Tdap and 1152 Td recipients were included; of these, 175 persons from Tdap
      group were available at the final study bleed point. Nearly all adolescents in
      both groups had diphtheria antibody levels >=0.1 IU/mL 1 month after vaccination,
      which were maintained in >=95% of vaccinees at 5 and 10 years. Among adults,
      >=94% had diphtheria antibody levels >=0.1 IU/mL 1 month after vaccination, which
      were maintained in >=80% at 5 and 10 years. Nearly all participants had tetanus
      antibodies >=0.1 IU/mL throughout the study. PT antibodies declined to pre
      vaccination levels approximately 5 years post-vaccination; FHA, PRN and FIM
      antibodies waned at 5 and 10 years but remained several-fold higher than pre
      vaccination levels. CONCLUSIONS: Tdap and Td provide long-lasting protective
      immune responses against diphtheria and tetanus. Pertussis antibodies following
      Tdap generally exceeded pre-vaccination levels throughout the study, but showed
      substantial waning. These data may inform discussion of the need for repeat Tdap
      booster vaccinations among adults. TRIAL REGISTRATION: The original phase III
      clinical trial, as well as the 1-, 3-, and 5-year serology follow-up studies were
      conducted prior to mandatory registration. The 10-year serology follow-up data
      collection was performed as part of a repeat Tdap administration clinical trial
      that was registered under clinicaltrials.gov number NCT01439165.

PMID- 29573877
TI  - T-cell responses against Malaria: Effect of parasite antigen diversity and
      relevance for vaccine development.
AB  - The on-going agenda for global malaria elimination will require the development
      of additional disease control and prevention measures since currently available
      tools are showing signs of inadequacy. Malaria vaccines are seen as one such
      important addition to the control arsenal since vaccines have proven to be highly
      effective public health tools against important human diseases. Both cell
      mediated and antibody responses are generally believed to be important for
      malaria parasite control, although the exact targets of T and B cell responses
      against malaria have not been clearly defined. However, our current understanding
      of the immune response to malaria suggests that T cell responses against multiple
      antigenic targets may potentially be key for the development of a highly
      efficacious malaria vaccine. This review takes a comprehensive look at the
      available literature on T cell-mediated immunity against all human stages of the
      malaria parasite and the effect of antigen diversity on these responses. The
      implications of these interrelationships for the development of an effective
      vaccine for malaria are also highlighted.

PMID- 29573878
TI  - Long-term immunity to hepatitis B following vaccination in infancy: Real-world
      data analysis.
AB  - BACKGROUND: Hepatitis B virus (HBV) vaccination has decreased the prevalence of
      chronic HBV infections and their sequelae. However, whether vaccination at birth
      provides lifelong protection is unclear. OBJECTIVE: To assess long-term immunity
      following neonatal HBV immunization in a large population-based cohort. METHODS:
      Using the database of a 2 million member sick fund in Israel, we identified all
      subjects born after introduction of universal HBV vaccination in Israel (January
      1992 through December 2014), that were tested for hepatitis B surface antibody
      (anti-HBs Ab's). Years since vaccination were categorized into 5-year groups and
      linear trends in the seroprevalence of HBV immunity were calculated. Anamnestic
      response and presence of Hepatitis B surface antigen (HBs Ag) were assessed.
      RESULTS: Included were 20,634 tested individuals. Mean (+/-SD) age at testing was
      14.8 (+/-5.4) years. Mean anti-HBs Ab levels declined with time to 16.39 mIU/ml
      in the 15-20 year group (P < 0.001). The proportion of negative results increased
      gradually (P < 0.001) to 66.7% after 15 years. Anamnestic response assessment
      showed that 604 of 644 seronegative subjects (93.8%, 95% CI: 91.6-95.5%) became
      seropositive after a booster dose. HBs Ag was identified in 91 of the 20,634 (4.4
      per 1000 study participants). CONCLUSIONS: Following vaccination, anti-HB's Ab's
      progressively decline, with only a third of the population retaining protective
      levels after 15 years. In adolescence, anamnestic response shows that nearly all
      revaccinated adolescents exhibit immunity. A low rate of Hepatitis B infection
      was demonstrated despite vaccination of nearly all newborns.

PMID- 29573879
TI  - Preclinical and clinical otoprotective applications of cell-penetrating peptide D
      JNKI-1 (AM-111).
AB  - There is a growing interest in the auditory community to develop novel
      prophylactic and therapeutic drugs to prevent permanent sensorineural hearing
      loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK)
      pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK
      pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has
      shown promise as both a prophylactic and therapeutic agent for acute cochlear
      injury. A number of pre-clinical and clinical studies have determined the impact
      of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective
      therapeutic profile, local route of administration, and ability to diffuse across
      cellular membranes rapidly using both active and passive transport makes D-JNK-1
      a promising oto-protective drug. In this review article, we discuss the
      application of D-JNKI-1 in various auditory disorders as well as its
      pharmacological properties and distribution in the cochlea.

PMID- 29573881
TI  - Auditory and language outcomes in children with unilateral hearing loss.
AB  - OBJECTIVES: Children with unilateral hearing loss (UHL) are being diagnosed at
      younger ages because of newborn hearing screening. Historically, they have been
      considered at risk for difficulties in listening and language development. Little
      information is available on contemporary cohorts of children identified in the
      early months of life. We examined auditory and language acquisition outcomes in a
      contemporary cohort of early-identified children with UHL and compared their
      outcomes at preschool age with peers with mild bilateral loss and with normal
      hearing. DESIGN: As part of the Mild and Unilateral Hearing Loss in Children
      Study, we collected auditory and spoken language outcomes on children with
      unilateral, bilateral hearing loss and with normal hearing over a four-year
      period. This report provides a cross-sectional analysis of results at age 48
      months. A total of 120 children (38 unilateral and 31 bilateral mild, 51 normal
      hearing) were enrolled in the study from 2010 to 2015. Children started the study
      at varying ages between 12 and 36 months of age and were followed until age 36-48
      months. The median age of identification of hearing loss was 3.4 months (IQR:
      2.0, 5.5) for unilateral and 3.6 months (IQR: 2.7, 5.9) for the mild bilateral
      group. Families completed an intake form at enrolment to provide baseline child
      and family-related characteristics. Data on amplification fitting and use were
      collected via parent questionnaires at each annual assessment interval. This
      study involved a range of auditory development and language measures. For this
      report, we focus on the end of follow-up results from two auditory development
      questionnaires and three standardized speech-language assessments. Assessments
      included in this report were completed at a median age of 47.8 months (IQR: 38.8,
      48.5). Using ANOVA, we examined auditory and language outcomes in children with
      UHL and compared their scores to children with mild bilateral hearing loss and
      those with normal hearing. RESULTS: On most measures, children with UHL performed
      poorer than those in the mild bilateral and normal hearing study groups. All
      children with hearing loss performed at lower levels compared to the normal
      hearing control group. However, mean standard scores for the normal hearing group
      in this study were above normative means for the language measures. In
      particular, children with UHL showed gaps compared to the normal hearing control
      group in functional auditory listening and in receptive and expressive language
      skills (three quarters of one standard deviation below) at age 48 months. Their
      performance in receptive vocabulary and speech production was not significantly
      different from that of their hearing peers. CONCLUSIONS: Even when identified in
      the first months of life, children with UHL show a tendency to lag behind their
      normal hearing peers in functional auditory listening and in receptive and
      expressive language development.

PMID- 29573880
TI  - Responses of neurons in the feline inferior colliculus to modulated electrical
      stimuli applied on and within the ventral cochlear nucleus; Implications for an
      advanced auditory brainstem implant.
AB  - Auditory brainstem implants (ABIs) can restore useful hearing to persons with
      deafness who cannot benefit from cochlear implants. However, the quality of
      hearing restored by ABIs rarely is comparable to that provided by cochlear
      implants in persons for whom those are appropriate. In an animal model, we
      evaluated elements of a prototype of an ABI in which the functions of
      macroelectrodes on the surface of the dorsal cochlear nucleus would be integrated
      with the function of multiple penetrating microelectrodes implanted into the
      ventral cochlear nucleus. The surface electrodes would convey most of the range
      of loudness percepts while the intranuclear microelectrodes would sharpen and
      focus pitch percepts. In the present study, stimulating electrodes were implanted
      chronically on the surface of the animal's dorsal cochlear nucleus (DCN) and also
      within their ventral cochlear nucleus (VCN). Recording microelectrodes were
      implanted into the central nucleus of the inferior colliculus (ICC). The
      electrical stimuli were sinusoidally modulated stimulus pulse trains applied on
      the DCN and within the VCN. Temporal encoding of neuronal responses was
      quantified as vector strength (VS) and as full-cycle rate of neuronal activity in
      the ICC. VS and full-cycle AP rate were measured for 4 stimulation modes;
      continuous and transient amplitude modulation of the stimulus pulse trains, each
      delivered via the macroelectrode on the surface of the DCN and then by the
      intranuclear penetrating microelectrodes. In the proposed clinical device the
      functions of the surface and intranuclear microelectrodes could best be
      integrated if there is minimal variation in the neuronal responses across the
      range of modulation depth, modulation frequencies, and across the four
      stimulation modes. In this study VS did vary as much as 34% across modulation
      frequency and modulation depth within a stimulation mode, and up to 40% between
      modulation modes. However, these intra- and inter-mode variances differed for
      different stimulation rates, and at 500 Hz the inter-mode differences in VS and
      across the range of modulation frequencies and modulation depths was<Roman> =
      </Roman>24% and the intra-modal differences were<Roman> = </Roman>15%. The
      findings were generally similar for rate encoding of modulation depth, although
      the depth of transient amplitude modulation delivered by the surface electrode
      was weakly encoded as full-cycle rate. Overall, our findings support the concept
      of a clinical ABI that employs surface stimulation and intranuclear
      microstimulation in an integrated manner.

PMID- 29573883
TI  - Sexual Violence on Campus: Differences Across Gender and Sexual Minority Status.
AB  - PURPOSE: Sexual violence is a pervasive problem on university campuses. Although
      previous work has documented greater vulnerability for sexual violence among
      sexual and gender minority students, little is known about contextual variation
      in vulnerability to this kind of violence. The goals of the current study were
      (1) to identify vulnerability among sexual and gender minority students with
      regard to sexual violence, and (2) to explore if the context of this violence
      differs across sexual and gender minority status. METHODS: Undergraduate students
      (ages 18-24) from six francophone universities in Quebec, Canada (N = 4,264)
      completed online questionnaires regarding their experience of sexual violence, as
      well as the context of these acts (e.g., the gender of the perpetrator, the
      status of the perpetrator, and the location of the violence). They also provided
      information regarding their sexual and gender minority status. Binary logistic
      regressions were conducted to assess for variation in experiencing sexual
      violence across sexual and gender minority status. RESULTS: Transgender/nonbinary
      students generally reported higher levels of sexual violence than their cisgender
      peers, while variation occurred with regard to vulnerability across sexual
      identity subgroups. Few differences in context were observed across sexual
      minority identity. Transgender/nonbinary students were significantly more likely
      to report sexual violence in athletic contexts and during volunteering activities
      compared to their cisgender peers. CONCLUSIONS: Findings highlight the higher
      levels of vulnerability for sexual violence among gender minority and some sexual
      minority university students. They also point to the contexts in which such
      violence occurs, suggesting specific strategies for prevention.

PMID- 29573882
TI  - Unraveling the Structure and Mechanism of the MST(ery) Enzymes.
AB  - The menaquinone, siderophore, and tryptophan (MST) enzymes transform chorismate
      to generate precursor molecules for the biosynthetic pathways defined in their
      name. Kinetic data, both steady-state and transient-state, and X-ray crystal
      structures indicate that these enzymes are highly conserved both in mechanism and
      in structure. Because these enzymes are found in pathogens but not in humans,
      there is considerable interest in these enzymes as drug design targets. While
      great progress has been made in defining enzyme structure and mechanism,
      inhibitor design has lagged behind. This review provides a detailed description
      of the evidence that begins to unravel the mystery of how the MST enzymes work,
      and how that information has been used in inhibitor design.

PMID- 29573884
TI  - Ten years of research with the Socially Evaluated Cold Pressor Test: Data from
      the past and guidelines for the future.
AB  - Ten years ago, the Socially Evaluated Cold Pressor Test (SECPT) was introduced as
      a standardized protocol for the efficient experimental stress induction in
      humans. In short, the 3 min SECPT, which can be conducted by only a single
      experimenter, combines a physiological challenge (hand immersion into ice water)
      with socio-evaluative elements. The purpose of this article is twofold. First, we
      aim to evaluate the subjective and physiological responses elicited by the SECPT.
      To this end, we pooled data from 21 studies from our lab and systematically
      analyzed the response profile to the SECPT. Our analyses show that the SECPT
      leads, both in men and women, to striking increases in subjective stress levels,
      autonomic arousal, and cortisol, albeit the cortisol response is typically
      somewhat less pronounced than in the Trier Social Stress Test. Second, we aim to
      provide guidelines for conducting the SECPT, in order to foster homogenization of
      the SECPT procedure across (and within) labs. In sum, we argue that the SECPT is
      a highly efficient tool to induce stress and activate major stress systems in a
      laboratory context, in particular if the guidelines that we outline here are
      followed.

PMID- 29573885
TI  - Use of bilaminar grafts as life-saving interventions for severe burns: A single
      center experience.
AB  - BACKGROUND: Skin coverage remains a significant hurdle in large-sized burns.
      Recent advances have allowed to grow Bilaminar Cultured Skin Autografts (BCSGs)
      from patients' own donor sites. The aim of this study was to report long-term
      outcomes in patients with large-sized burns having received BCSGs. METHODS: Nine
      patients received BCSGs from January 2010 to May 2015. Except one patient who
      died during hospitalization, all patients were contacted. Four agreed to partake
      in the study. Patients were tested with the Vancouver Scar Scale (VSS), QuickDASH
      questionnaire and Burn Specific Health Scale (BSHS). Incisional biopsies of BCSGs
      were compared with patients' autografts. RESULTS: From nine patients, mean age
      was 40 years and mean TBSA was 70.3%. For the four patients included, score
      averaged was 2.25 on the VSS, 29.5 on QuickDASH, 36/36 for psychosocial items and
      63/84 for functional abilities on the BSHS. Compared with autografts, BCSGs
      demonstrated better pliability VSS and functionality. Biopsies showed no evidence
      of malignancy or atypical changes, but areas of hyperpigmentation. CONCLUSION:
      This is the first report investigating the long-term outcome of a newly developed
      BCSG. BCSGs demonstrated comparable results with patients' autografts, functional
      outcomes on self-reported questionnaires and excellent psychological states.
      Precaution given the extensive unexpected hyperpigmentation must be taken and a
      randomized controlled study is underway.

PMID- 29573886
TI  - Wet in situ transesterification of spent coffee grounds with supercritical
      methanol for the production of biodiesel.
AB  - This work introduces biodiesel production from wet spent coffee grounds (SCGs)
      with supercritical methanol without any pre-drying process. Supercritical
      methanol and subcritical water effectively produced biodiesel via in situ
      transesterification by inducing more porous SCG and enhancing the efficiency of
      lipid extraction and conversion. It was also found that space loading was one of
      the critical factors for biodiesel production. An optimal biodiesel yield of
      10.17 wt% of dry SCG mass (86.33 w/w% of esterifiable lipids in SCG) was obtained
      at reaction conditions of 270  degrees C, 90 bars, methanol to wet SCG ratio 5:1,
      space loading 58.4 ml/g and reaction time 20 min. Direct use of wet SCG waste as
      feedstock for supercritical biodiesel production eliminates the conventional
      dying process and the need of catalyst and also reduces environmental problems
      caused by landfill accumulation.

PMID- 29573887
TI  - Artifacts in Shear Wave Elastography Images of Thyroid Nodules.
AB  - The purpose of the study described here was to evaluate the presence and types of
      artifacts seen in color elastograms in thyroid elastography using shear wave
      elastography. This Health Insurance Portability and Accountability Act of 1996
      (HIPAA)-compliant study was approved by the ethics committee of our institution,
      and all patients provided written informed consent. One hundred seventy-eight
      patients (40 men and 138 women; mean age, 49 y; range, 19-84 y) were enrolled for
      a total of 241 thyroid nodules. After a short ultrasound (US) examination, SWE
      images were acquired at multiple levels in the nodule in transverse and
      longitudinal orientations. A total of 1297 images were obtained from 241 nodules
      for an average of 5.4 +/-  2.7 (mean +/- standard deviation) images per nodule. A
      retrospective review of all images was performed by one reviewer experienced in
      thyroid elastography. Two hundred eighty images (21.6%) were rated as good
      quality, and 112 (8.6%) were rated as moderate quality without artifacts. A total
      of 905 (69.8%) images had some artifact present, though most of these images
      (73.4%) were still interpretable. Two hundred forty-one images (18.6% of all
      images) were considered uninterpretable because of artifact. The most common
      types of artifacts were due to operator error (44.6% of all images), primarily
      compression (36.5% of all images). Other artifacts seen were due to anatomy
      (presence of carotid pulsation or adjacent to thyroid or location in isthmus, 11%
      of all images), nodule characteristics (cystic and calcified nodules or large
      nodules with lack of penetration, 17% of all images) and other artifacts that
      could not be explained by the prior mentioned causes (13% of all images). Our
      study indicates that artifacts are common in elastography images. Operator error
      was the most common type of artifact we saw. This should be easily correctable by
      adequate knowledge and recognition with subsequent correction of the artifacts.

PMID- 29573888
TI  - Effects of Low-Intensity Pulsed Ultrasound for Preventing Joint Stiffness in
      Immobilized Knee Model in Rats.
AB  - The purpose of this study was to examine the effect of low-intensity pulsed
      ultrasound (LIPUS) in preventing joint stiffness. Unilateral knee joints were
      immobilized in two groups of rats (n = 6/period/group). Under general anesthesia,
      the immobilized knee joints were exposed to LIPUS for 20 min/d, 5 d/wk, using an
      existing LIPUS device (LIPUS group, 1.5-MHz frequency, 1.0-kHz repetition cycle,
      200-us burst width and 30-mW/cm2 power output) until endpoints (2, 4 or 6 wk). In
      the control group, general anesthesia alone was administered in the same manner
      as in the other group. The variables compared between the groups included joint
      angles; histologic, histomorphometric and immunohistochemical analyses;
      quantitative reverse transcription polymerase chain reactions; and tissue
      elasticity. LIPUS had a preventive effect on joint stiffness, resulting in
      decreased adhesion, fibrosis and inflammation and hypoxic response after joint
      immobilization.

PMID- 29573889
TI  - Effects of long-term consumption of broccoli sprouts on inflammatory markers in
      overweight subjects.
AB  - BACKGROUND & AIMS: Broccoli sprouts represent an interesting choice of healthy
      food product as they are rich in glucosinolates and their cognate bioactive
      metabolites, isothiocyanates able to counteract the negative effects of diverse
      pathologies. As obesity is linked to an inflammatory component, the aim of the
      study was to evaluate the anti-inflammatory action of broccoli sprouts in
      overweight adult subjects. METHODS: An in vivo controlled study was performed in
      40 healthy overweight subjects (ClinicalTrials.gov ID NCT 03390855). Treatment
      phase consisted on the consumption of broccoli sprouts (30 g/day) during 10 weeks
      and the follow-up phase of 10 weeks of normal diet without consumption of these
      broccoli sprouts. Anthropometric parameters as body fat mass, body weight, and
      BMI were determined. Inflammation status was assessed by measuring levels of TNF
      alpha, IL-6, IL-1beta and C-reactive protein. RESULTS: IL-6 levels significantly
      decreased (mean values from 4.76 pg/mL to 2.11 pg/mL with 70 days of broccoli
      consumption, p < 0.001) and during control phase the inflammatory levels were
      maintained at low grade (mean values from 1.20 pg/mL to 2.66 pg/mL, p < 0.001). C
      reactive protein significantly decreased as well. CONCLUSIONS: This study
      represents an advance in intervention studies as the broccoli sprouts were
      included in a daily dietary pattern in quantities that reflect a real
      consumption. Further studies are necessary to elucidate the role of this healthy
      rich and nutritious food product, but these promising results support the current
      evidence on the healthy properties of Brassica varieties.

PMID- 29573890
TI  - Corrigendum to "Mindfulness-based relapse prevention for substance craving"
      [Addictive Behaviors 38 (2013) 1563-1571].

PMID- 29573891
TI  - Adolescents' perceptions of flavored tobacco products, including E-cigarettes: A
      qualitative study to inform FDA tobacco education efforts through videogames.
AB  - INTRODUCTION: Flavored tobacco products have been shown to appeal to youth,
      however tobacco control strategies have traditionally not focused on these
      products. To inform the adaptation of an existing videogame to focus on the
      prevention of flavored tobacco product use, this study explored adolescents'
      perceptions, beliefs, and social norms surrounding these products, including
      flavored e-cigarettes. METHODS: We conducted and analyzed transcripts from seven
      focus groups with 11-17-year-old adolescents (n = 33) from after-school programs
      in CT and CA in 2016. Participants discussed flavored tobacco product beliefs and
      experiences, and how these compared to traditional cigarettes. RESULTS: Thematic
      analysis of transcripts revealed that participants could name flavors in tobacco
      products, even though few discussed first-hand experience with the products. Most
      groups perceived that flavored tobacco product and flavored e-cigarette use
      facilitated peer approval and acceptance. All groups discussed how youth could
      easily access flavored tobacco products, including e-cigarettes. Flavoring was a
      salient aspect of e-cigarette advertisements; however the groups did not recall
      exposure to other types of flavored tobacco product counter-marketing.
      CONCLUSIONS: These data can help inform the development of tobacco control
      strategies, novel interventions (such as videogames), and future FDA efforts to
      prevent adolescent tobacco product use through education and risk communication.

PMID- 29573892
TI  - Creating a conceptual model for family caregivers of older adults intervention
      research: A narrative review of learned resourcefulness, resourcefulness, and the
      transtheoretical model.
AB  - Providing and maintaining optimal care is challenging for older family caregivers
      who are caring for disabled older adults. Learned Resourcefulness can facilitate
      family caregivers' self-help strategies, and Resourcefulness can facilitate help
      seeking from others. However, little is known about how older family caregivers
      can effectively maintain and adapt self-help and help-seeking strategies over
      time, especially as the dynamic nature of caregiving for disabled older adults
      demands change. To this end, the Transtheoretical model (TTM) provides useful
      constructs that address family caregivers' readiness to change their self-help
      and help-seeking behaviors. This paper reviews relevant literature regarding
      Learned Resourcefulness, Resourcefulness, and the TTM. The proposed conceptual
      model incorporates constructs from the TTM integrated with Learned
      Resourcefulness and Resourcefulness strategies to aid in the development and
      testing of interventions that are designed to promote the quality of life and
      health of older family caregivers while they are providing care to disabled older
      adults.

PMID- 29573893
TI  - Health care providers' perceptions of family caregivers' involvement in
      consultations within a geriatric hospital setting.
AB  - This study explored health professionals' (HPs') experiences of interacting with
      family care-givers (FCs), and the strategies they employ during these
      interactions. Qualitative methods involved audio-taped and transcribed in-depth
      semi-structured interviews with 21 HPs (doctors, nurses) from the geriatric wards
      of two tertiary hospitals. Framework methods were used to analyze data. Seven
      main themes emerged: Variation in family behaviours; FCs face many challenges;
      Psychosocial factors influence FCs' behaviours; Attitudes, competing
      responsibilities and lack of resources influencing HPs' strategies and
      behaviours; Strategies employed by HPs to improve communication; HPs' self-care
      strategies; Impact of interactions on HPs and the healthcare system. Inter
      relationships between the themes were then integrated into a three-part model.
      This study offered insights into HPs' perspectives, experiences, and behaviours
      in geriatric consultations where FCs are present. Findings emphasised the need
      for HP training programs to improve communication and collaboration between HPs,
      patients, and FCs.

PMID- 29573894
TI  - The Effectiveness of Mini-C-Arm Fluoroscopy for the Closed Reduction of Distal
      Radius Fractures in Adults: A Randomized Controlled Trial.
AB  - PURPOSE: Most distal radius (DR) fractures are initially managed with closed
      reduction and orthosis application. Mini-C-arm fluoroscopy provides assessment of
      reduction quality in real time. Our null hypothesis was that there would be no
      difference in the reduction quality of DR fractures in the emergency department
      when using mini-C-arm fluoroscopy during reduction compared with standard
      reduction techniques (evaluating reduction quality with orthogonal radiographs
      taken in an orthosis). METHODS: Sixty-three consecutive patients with closed DR
      fractures requiring reduction between April 2015 and April 2017 were
      prospectively randomized to standard versus fluoroscopically aided reductions.
      Reductions were performed by orthopedic surgery residents. The primary outcome
      measurement was reduction quality (radial height, radial inclination, ulnar
      variance, and volar tilt) as measured on postreduction radiographs. RESULTS:
      Standard reductions were performed in 34 patients and fluoroscopically aided
      reductions in 29 patients. The 2 groups were similar in regards to all potential
      confounders that were analyzed. No differences in postreduction radial height,
      radial inclination, ulnar variance, or volar tilt were noted. Overall reduction
      attempts and subjective difficulty of fracture reduction were increased when
      using fluoroscopy. The rate of initial operative management did not differ
      between groups. CONCLUSIONS: The use of mini-C-arm fluoroscopy during the initial
      closed reduction of adult DR fractures results in equivalent postreduction
      radiographic parameters when compared with conventional reduction techniques.
      Additional research regarding time spent in the emergency department and overall
      cost could elucidate potential benefits of fluoroscopically aided DR fracture
      reduction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

PMID- 29573895
TI  - The Effect of Dorsally Angulated Distal Radius Deformities on Carpal Kinematics:
      An In Vitro Biomechanical Study.
AB  - PURPOSE: The purpose was to quantify the effect of distal radius dorsal
      angulation (DA) on carpal kinematics and the relative roles of the radiocarpal
      and midcarpal joints during wrist motion. METHODS: Six cadaveric specimens (69 +/
      17 y) were mounted at 90 degrees  elbow flexion in a custom wrist motion
      simulator. The wrist was guided through planar passive flexion and extension
      motion trials (~ 5 degrees /s). A custom modular distal radius implant was used
      to simulate native alignment and 3 distal radius DA deformities (10 degrees , 20
      degrees , 30 degrees ). An optical tracking system captured carpal bone motion,
      from which radiocarpal and midcarpal joint motion was determined. RESULTS: The
      radiocarpal joint made a greater contribution to wrist motion than the midcarpal
      joint in flexion, and the midcarpal joint made a greater contribution to motion
      than the radiocarpal joint in wrist extension. Increasing DA caused the
      radiocarpal joint contribution to increase throughout the motion arc, with the
      effect being more pronounced in wrist flexion. Conversely, as DA increased, the
      midcarpal joint contributed less rotation to the total wrist motion and its
      overall motion arc decreased; the magnitude of effect was greater in wrist
      extension. Dorsal angulation resulted in increased lunate flexion with respect to
      the distal radius. CONCLUSIONS: Our findings agree with current literature that
      suggests that, in an uninjured wrist, the radiocarpal joint predominates flexion,
      and the midcarpal joint predominates extension. In addition, the radiocarpal
      joint has an amplified contribution in wrist flexion with greater DA malunion.
      CLINICAL RELEVANCE: The altered contributions of the radiocarpal and midcarpal
      joints may contribute to pain, stiffness, and the development of arthritis, which
      is commonly seen at the radiocarpal joint after malunion of the distal radius.

PMID- 29573896
TI  - Kienbock Disease in the Skeletally Immature Patient.
AB  - Kienbock disease is uncommon in skeletally immature patients. Although there is
      no gold standard treatment for Kienbock disease in the skeletally immature
      patient, surgical and nonsurgical treatment options have been shown to be
      effective. Initial immobilization with a cast, protection with an orthosis, and
      avoidance of repetitive forceful activities have been shown to be effective in
      some cases. Surgery may be offered to the skeletally immature patient when
      nonsurgical treatment is ineffective. Among several surgical techniques used for
      treatment in the skeletally immature patient with Kienbock disease, distal radial
      osteotomies have been the most frequently performed surgery; however, radial
      overgrowth is a concern. There is a great potential for revascularization and
      remodeling of the lunate in the skeletally immature patients with Kienbock
      disease. Good and excellent clinical and radiological outcomes can be achieved
      with both nonsurgical and surgical treatments.

PMID- 29573897
TI  - Documenting Combined Congenital Upper Limb Anomalies Using the Oberg, Manske, and
      Tonkin Classification: Implications for Epidemiological Research and Outcome
      Comparisons.
AB  - PURPOSE: Congenital upper limb anomalies (CULAs) exhibit a wide spectrum of
      phenotypic manifestations. To help the clinician evaluating this variety of
      CULAs, the Oberg, Manske, and Tonkin (OMT) classification was recently
      introduced. The OMT classification allows for documentation of combined hand
      anomalies. However, subsequent epidemiological and validation studies using the
      OMT scheme commonly registered only the main anomaly per arm. This study
      illustrates both the deficits of single diagnosis documentation as well as the
      merits of registering every anomaly for epidemiological research, outcome
      comparison, and overall applicability of the classification. METHODS: We
      retrospectively reviewed patients visiting the Erasmus MC - Sophia Children's
      Hospital between 2012 and 2014. All congenital anomalies of both limbs were
      classified according to the OMT scheme. The frequency of combined diagnoses as
      well as recurrent combinations were analyzed. The relation to the coregistered
      syndromes was studied. RESULTS: We included 746 patients, 79.5% of whom could be
      documented with a single OMT diagnosis. In 20.5%, a combination of OMT diagnoses
      was documented. We documented 149 different combinations: 102 were documented
      once, 47 were documented repeatedly (n = 196); for example, in patients with
      Greig syndrome. The prevalence of this syndrome was significantly higher in
      patients with a combination of radial polydactyly, ulnar polydactyly, and/or
      syndactyly (2.9% vs 33.3% and 60% in patients with 1 vs 2 and 3 diagnoses).
      CONCLUSIONS: Documentation of combined OMT diagnoses is required in a fifth of
      the patients. Not doing so will cause loss of phenotypic information and can
      hamper outcome comparison and epidemiological research. Documentation of combined
      OMT diagnoses can help to identify subgroups within a population, for example,
      patients with an underlying syndrome. Last, combined documentation of diagnoses
      improves flexibility of the classification and thereby better allows universal
      application. CLINICAL RELEVANCE: Consensus on the application of the OMT
      classification is critical to achieving the universal adoption of the system by
      hand surgeons and other medical professionals.

PMID- 29573898
TI  - Efficacy of prehospital administration of tranexamic acid in trauma patients: A
      meta-analysis of the randomized controlled trials.
AB  - OBJECTIVE: Antifibrinolytic agent tranexamic acid (TXA) has a potential clinical
      benefit for in-hospital patients with severe bleeding but its effectiveness in
      pre-hospital settings remains unclear. We conducted a systematic review and meta
      analysis to evaluate whether pre-hospital administration of TXA compared to
      placebo improve patients' outcomes? METHODS: PubMed, MEDLINE, Cochrane Library,
      WHO International Clinical Trials Registry Platform, Cochrane Central Register of
      Controlled Trials (CENTRAL), Scopus, clinicaltrials.gov and Google scholar
      databases were searched for a retrospective, prospective and randomized (RCT) or
      quasi-RCT studies that assessed the effect of prehospital administration of TXA
      versus placebo on the outcomes of trauma patients with significant hemorrhage.
      The main outcomes of interest were 24hour 30-day mortality and in-hospital
      thromboembolic complications. Two authors independently abstracted the data using
      a data collection form. Results from different studies were pooled for the
      analysis, when appropriate. RESULTS: Out of 92 references identified through the
      search, two analytical studies met the inclusion criteria. The effect of TXA on
      24-hour mortality had a pooled odds ratio (OR) of 0.49 (95% CI 0.28-0.85), 30-day
      mortality OR of 0.86 (95% CI, 0.56-1.32), and thromboembolic events OR of 0.74
      (95% CI, 0.27-2.07). CONCLUSION: Prehospital TXA appears to reduce early
      mortality in trauma patients. The pooled analysis also shows a trend toward lower
      30-day mortality and reduced risk of thromboembolic events. Additional randomized
      controlled clinical trials are needed to determine the significance of these
      trends.

PMID- 29573899
TI  - National characteristics of Emergency Department visits by patients with cancer
      in the United States.
AB  - PURPOSE: The Emergency Department (ED) is an important venue for the care of
      patients with cancer. We sought to describe the national characteristics of ED
      visits by patients with cancer in the United States. METHODS: We performed an
      analysis of 2012-2014 ED visit data from the National Hospital Ambulatory Medical
      Care Survey (NHAMCS). We included adult (age>=18years) ED patients, stratified by
      history of cancer. Using the NHAMCS survey design and weighting variables, we
      estimated the annual number of adult ED visits by patients with cancer. We
      compared demographics, clinical characteristics, ED resource utilization, and
      disposition of cancer vs. non-cancer patients. RESULTS: There were an estimated
      104,836,398 annual ED visits. Patients with cancer accounted for an estimated
      3,879,665 (95% CI: 3,416,435-4,342,895) annual ED visits. Compared with other ED
      patients, those with cancer were older (mean 64.8 vs. 45.4years), more likely to
      arrive by Emergency Medical Services (28.0 vs. 16.9%), and experienced longer
      lengths of ED stay (mean 4.9 vs. 3.8h). Over 65% of ED patients with cancer
      underwent radiologic imaging. Patients with cancer almost twice as likely to
      undergo CT scanning; four times more likely to present with sepsis; twice as
      likely to present with thrombosis, and three times more likely to be admitted to
      the hospital than non-cancer patients. CONCLUSIONS: Patients with cancer comprise
      nearly 4 million ED visits annually. The findings highlight the important role of
      the ED in cancer care and need for addressing acute care conditions in patients
      with cancer.

PMID- 29573900
TI  - Usefulness of optic nerve ultrasound to predict clinical progression in multiple
      sclerosis.
AB  - INTRODUCTION: Progressive neuronal and axonal loss are considered the main causes
      of disability in patients with multiple sclerosis (MS). The disease frequently
      involves the visual system; the accessibility of the system for several
      functional and structural tests has made it a model for the in vivo study of MS
      pathogenesis. Orbital ultrasound is a non-invasive technique that enables various
      structures of the orbit, including the optic nerve, to be evaluated in real time.
      MATERIAL AND METHODS: We conducted an observational, ambispective study of MS
      patients. Disease progression data were collected. Orbital ultrasound was
      performed on all patients, with power set according to the 'as low as reasonably
      achievable' (ALARA) principle. Optical coherence tomography (OCT) data were also
      collected for those patients who underwent the procedure. Statistical analysis
      was conducted using SPSS version 22.0. RESULTS: Disease progression was
      significantly correlated with ultrasound findings (P=.041 for the right eye and
      P=.037 for the left eye) and with Expanded Disability Status Scale (EDSS) score
      at the end of the follow-up period (P=.07 for the right eye and P=.043 for the
      left eye). No statistically significant differences were found with relation to
      relapses or other clinical variables. DISCUSSION: Ultrasound measurement of optic
      nerve diameter constitutes a useful, predictive factor for the evaluation of
      patients with MS. Smaller diameters are associated with poor clinical progression
      and greater disability (measured by EDSS).

PMID- 29573901
TI  - Corrigendum to "Catheter Foam Sclerotherapy of the Great Saphenous Vein, with
      Perisaphenous Tumescence Infiltration and Saphenous Irrigation" [Eur J Vasc
      Endovasc Surg (2017) 629-635].

PMID- 29573903
TI  - Response to Effects of pre-load variations on hemodynamic parameters with a
      pulsatile autoregulated artificial heart during the early post-operative period.

PMID- 29573902
TI  - Computed tomography underestimates rotator cuff pathology in patients with
      glenohumeral osteoarthritis.
AB  - BACKGROUND: Computed tomography (CT) is the standard assessment of glenoid
      morphology before shoulder arthroplasty and is commonly used to evaluate rotator
      cuff pathology in patients with glenohumeral osteoarthritis (GHOA). Magnetic
      resonance imaging (MRI) is not routinely used in this setting but has higher
      sensitivity in diagnosing full-thickness rotator cuff tears (RCT) and is
      considered the gold standard. The purpose of this study was to determine the
      sensitivity and specificity of CT in diagnosing full-thickness RCTs and compare
      the evaluation of fatty infiltration and muscle atrophy on CT vs. MRI in the
      setting of GHOA. METHODS: In this retrospective case-controlled study, we
      identified 49 patients from a prospectively maintained 2-surgeon registry who
      received preoperative CT and MRI scans for the evaluation of GHOA between 2011
      and 2016. Three fellowship-trained shoulder surgeons assessed rotator cuff
      integrity, fatty infiltration, and muscle atrophy in the CT and MRI scans.
      RESULTS: CT sensitivity and specificity were 20% and 95.5%, respectively. Fatty
      infiltration was significantly lower on CT for the supraspinatus (P = .003),
      infraspinatus (P < .001), and subscapularis (P = .0182), whereas muscle atrophy
      was significantly lower on CT for only the supraspinatus (P = .0023).
      CONCLUSIONS: Our results suggest that CT underestimates the frequency of full
      thickness RCTs and the severity of fatty infiltration and muscle atrophy in the
      setting of GHOA before total shoulder arthroplasty.

PMID- 29573904
TI  - Causes of Emergency Department Overcrowding and Blockage of Access to Critical
      Services in Beijing: A 2-Year Study.
AB  - BACKGROUND: Emergency department (ED) overcrowding is a serious issue worldwide.
      OBJECTIVES: This study was done to evaluate the degree of overcrowding in local
      "teaching hospitals" in Beijing, and to ascertain the apparent root causes for
      the pervasive degree of overcrowding in these EDs. METHODS: This is a multicenter
      cross-sectional study. The studied population included all ED patients from 18
      metropolitan teaching hospital EDs in Beijing for calendar years 2013 and 2014.
      Patient characteristics, and the primary reasons that these patients sought care
      in these EDs, are described. RESULTS: The total numbers of annual emergency
      visits were 1,554,387 and 1,615,571 in 2013 and 2014, respectively. High acuity
      cases accounted for 4.6% and 5.5% of the total annual emergency visits in 2013
      and 2014, respectively. The percentage of patients placed into "Observation"
      beds, which were created to accommodate patients deemed to have problems too
      complex to be treated in an inpatient bed, or to accommodate patients simply
      needing chronic care, was 11.9% and 13.1% in 2013 and 2014, respectively. The ED
      boarded patients accounted for 2.71% and 2.6% of the total annual emergency
      visits in 2013 and 2014, respectively. The average waiting time to admit the ED
      boarded patients was 37.1 h and 36.2 h in 2013 and 2014, respectively.
      Respiratory symptoms were the most common presenting complaints, and an upper
      respiratory infection was the most common ED diagnosis. Patients who had
      pneumonia or various manifestations of end-stage diseases, such as advanced
      dementia or multiple organ dysfunction, were the most common characteristics of
      patients who had stays in "Observation" units. CONCLUSIONS: One principal reason
      for ED crowding in Beijing lies in the large numbers of patients who persist in
      the expectation of receiving ongoing care in the ED for minor illnesses. However,
      as is true in many nations, one of the other most important root causes of ED
      crowding is "access block," the inability to promptly move patients deemed by
      emergency physicians to need inpatient care to an inpatient bed for that care.
      However, in our system, another challenge, not widely described as a contributor
      to crowding in other nations, is that doctors assigned to inpatient services have
      been empowered to refuse to admit patients perceived to have overly "complex"
      needs. Further, patients with multisystem illnesses or end-stage status, who need
      ongoing chronic care to manage activities of daily living, have begun to populate
      Beijing EDs in increasing numbers. This is an issue with various root causes.

PMID- 29573905
TI  - Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell
      transplantation (HSCT): A retrospective analysis and a proposal of treatment on
      behalf of the Grupo Espanol De Trasplante de Medula Osea en Ninos (GETMON) and
      the Grupo Espanol de Trasplante Hematopoyetico (GETH).
AB  - Autoimmune hemolytic anemia (AIHA) is a complication of allogeneic hematopoietic
      stem cell transplantation (HSCT) associated with poor outcome. However, an
      optimal therapeutic approach is lacking. Between 2000 and 2015, 4099 allogeneic
      HSCT were performed in eight pediatric centers of the Grupo Espanol De Trasplante
      de Medula Osea en Ninos (GETMON) and six adult centers of the Grupo Espanol de
      Trasplante Hematopoyetico (GETH). Sixty cases of AIHA were registered with a
      cumulative incidence of 1.5% occurring at a median of 6 months after HSCT.
      Patients aged less than 15 years (P=.005), and patients using cord blood (P=.005)
      or an HLA mismatch donor (P=.005) were more likely to develop AIHA. Most patients
      were lymphopenic at the time of diagnosis of AIHA, including a low number of
      regulatory T lymphocytes (median 3/MUL). Median lines of treatment received for
      AIHA was 3 (range, 1-7). Almost all patients received corticosteroids (88%) and
      more than half received immunoglobulins or rituximab (63% and 67%, respectively).
      Complete resolution of AIHA was achieved in 33 of 60 cases (55%). Cumulative
      incidence of AIHA-related mortality was 17+/-6%. We found a correlation of AIHA
      outcome with age (better outcome in younger than 15 years, RR=1.87, P=.01) and
      rituximab response (higher rate of complete remission in patients responding to
      rituximab, RR=1.72, P=.025). We analyzed the factors involved in the response to
      rituximab and found a better response when there was ABO donor/receptor disparity
      (P=.014) and in those patients with B lymphocytes count above the median (38/MUL)
      (P=.05).Thirty-six of 60 patients survived yielding a disease free survival of
      52+/-8% at 40 months. In Cox analysis, age (children vs adults, HR: 8.19, CI 95%:
      2.39-28.12, P=.001) and AIHA outcome (complete remission vs partial remission/non
      response, HR: 4.18, CI 95%: 1.55-11.22, P=.005) were associated with a better
      survival. Our data suggest that patients who developed AIHA after HSCT are
      severely lymphopenic and have a high risk of mortality. Outcome is better in
      children and in patients treated with rituximab. We also propose an algorithm for
      treatment of AIHA after HSCT.

PMID- 29573906
TI  - Reply to DR. De Cassai et al.

PMID- 29573907
TI  - [Erratum to "The way forward in transfusion medicine, from a French
      perspective..." [Transfus. Clin. Biol. (25)(1) (2018)]].

PMID- 29573908
TI  - Accelerated long-term forgetting in asymptomatic APOE epsilon4 carriers.

PMID- 29573909
TI  - Multifractal characteristics of external anal sphincter based on sEMG signals.
AB  - Up to 40% of patients treated for rectal cancer suffer from therapy-related
      symptoms. Innervation injury is one of the suggested pathomechanisms of those
      symptoms hence the development of a valid, non-invasive tool for the assessment
      of neural systems is crucial. The aim of this work is to study the fractal
      properties of the surface electromyography signals obtained from patients
      suffering from rectal cancer. The anal sphincter activity was investigated for
      the group of 15 patients who underwent surgical treatment. Multifractal detrended
      fluctuation analysis was implemented to analyze the data, obtained at four
      different stages: one before treatment and three times after the surgery. The
      results from the standard detrended fluctuation analysis and empirical mode
      decomposition methods are presented and compared. The statistically significant
      differences between the stages of treatment were identified for the selected
      spectral parameters: width and maximum of the spectrum.

PMID- 29573910
TI  - Synthesis and investigations into the anticancer and antibacterial activity
      studies of beta-carboline chalcones and their bromide salts.
AB  - A series of sixteen beta-carbolines, bearing chalcone moiety at C-1 position,
      were prepared from easily accessible 1-acetyl-beta-carboline and various
      aldehydes under basic conditions followed by N2-alkylation using different alkyl
      bromides. The prepared compounds were evaluated for in vitro cytotoxicity against
      a panel of human tumor cell lines. N2-Alkylated-beta-carboline chalcones 13a-i
      represented the interesting anticancer activities compared to N2-unsubstituted
      beta-carboline chalcones 12a-g. Off the prepared beta-carbolines, 13g exhibited
      broad spectrum of activity with IC50 values lower than 22.5 uM against all the
      tested cancer cell lines. Further, the N2-alkylated-beta-carboline chalcone 13g
      markedly induced cell death in MDA-MB-231 cells by AO/EB staining assay. The most
      cytotoxic compound 13g possessed a relatively high drug score of 0.48.
      Additionally, the prepared beta-carboline chalcones displayed moderate
      antibacterial activities against tested bacterial strains.

PMID- 29573912
TI  - Trends in Periprosthetic Hip Infection and Associated Costs: A Population-Based
      Study Assessing the Impact of Hospital Factors Using National Data.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is an important cost driver in
      hip arthroplasty revisions, thus necessitating careful trend monitoring. Recent
      national trend data are lacking; we therefore assessed national PJI burden,
      trends in prevalence, and hospitalization costs. METHODS: We extracted data on
      hip arthroplasty revisions from the National Inpatient Sample (2003-2013; n =
      465,209). Trends in PJI prevalence and hospitalization costs were (1) assessed
      for the full cohort and (2) stratified by hospital teaching status, hospital bed
      size (<=299, 300-499, and >=500 beds), and hospital region (Northeast, Midwest,
      South, and West). The Cochran-Armitage trend test (PJI prevalence) and linear
      regression (hospitalization costs) determined significance of trends. Trends were
      adjusted for patient's age, gender, insurance type, race, Deyo-Charlson
      comorbidities, obesity, length of stay, and hospital characteristics. RESULTS:
      Overall, PJI prevalence was 15.0% (n = 70,011); adjusted prevalence increased
      from 13.1% in 2003 to 16.4% in 2013 (P < .0001), while adjusted median PJI
      hospitalization costs increased from $28,240 in 2003 to $31,529 in 2013 (P <
      .0001). Rural hospitals had the lowest PJI burden (12.5%; n = 4,525), while urban
      and teaching hospitals had the highest PJI burden (16.4%; n = 40,297). The
      stratified analyses, particularly in large hospitals (>500 beds), showed that PJI
      prevalence increased from 13.0% (2003) to 17.4% (2013; a 33.8% increase; P <
      .0001). Similarly, PJI revision hospitalization costs increased from a median of
      $27,490 (2003) to $31,312 (2013; a 14% increase; P < .0001). CONCLUSION: The
      burden of PJI in hip arthroplasty revision is increasing and-while additional
      research is needed-there appears to be a particular shift of revision burden to
      larger hospitals with increasing costs.

PMID- 29573911
TI  - Limonene promotes osteoblast differentiation and 2-deoxy-d-glucose uptake through
      p38MAPK and Akt signaling pathways in C2C12 skeletal muscle cells.
AB  - BACKGROUND: Limonene is a cyclic monoterpene (CTL) found in citrus fruits and
      many plant kingdoms. It has attracted attention as potential molecule due to its
      diverse biological activities. However, molecular mechanism involved in the
      osteogenic induction of CTL in C2C12 skeletal muscle cells remain unclear.
      PURPOSE: Skeletal development maintains the bone homeostasis through bone
      remodeling process. It coordinated between the osteoblast and osteoblast process.
      Osteoporosis is one of the most common bone diseases caused by a systemic
      reduction in bone mass. Recent osteoporosis treatment is based on the use of anti
      resorptive and bone forming drugs. However, long term use of these drugs is
      associated with serious side effects and strategies on the discovery of lead
      compounds from natural products for osteoblast differentiation are urgently
      needed. Therefore, we planned to find out the role of CTL on osteoblast
      differentiation and glucose uptake in C2C12 cells and its effect on signaling
      pathways. METHODS: Cell proliferation, alkaline phosphatase (ALP) activity,
      calcium deposition, genes, and proteins associated with osteoblast activation and
      glucose utilization were analysed. RESULTS: CTL did not affect the cell
      viability. CTL significantly increased ALP activity, calcium depositions and the
      expression of osteogenic specific genes such as Myogenin, Myogenic
      differentiation 1 (MyoD), ALP, Run-related transcription factor 2(RUNX2),
      osteocalcin (OCN). In addition, CTL induced the mRNA expression of bone
      morphogenetic proteins (BMP-2 BMP-4 BMP-6 BMP-7 BMP-9). CTL treatment enhanced 2
      Deoxy-d-glucose (2DG) uptake. Moreover, CTL stimulated the activation of p38
      mitogen activated protein kinase (p38MAPK), Protein kinase B (Akt), Extracellular
      signal related kinase (ERKs) by increasing phosphorylation. CTL treatment
      abolished p38 inhibitor (SB203580) mediated inhibition of osteoblast
      differentiation, but no effect was noted by ERKs specific inhibitor (PD98059).
      CONCLUSION: These results suggest that limonene induces osteoblast
      differentiation and glucose uptake through activating p38MAPK and Akt signaling
      pathways, confirming the molecular basis of the osteoblast differentiation by
      limonene in C2C12 skeletal muscle cells.

PMID- 29573913
TI  - Fresh Osteochondral Allograft Transplantation for Treatment of Large Cartilage
      Defects of the Femoral Head: A Minimum Two-Year Follow-Up Study of Twenty-Two
      Patients.
AB  - BACKGROUND: Controversy remains over the surgical management of large
      osteochondral lesions of the femoral head in young, active patients. The purpose
      of this study is to assess midterm clinical and radiographic outcomes after fresh
      osteochondral allograft transplantation (OAT) for large femoral head lesions at
      minimum 2-year follow-up. METHODS: A retrospective review of prospectively
      collected data was performed for 22 patients under the age of 50 years with
      defined femoral head osteochondral lesions who underwent fresh OAT between 2008
      and 2015. Patients were assessed clinically using the modified Harris Hip Score
      (mHHS) preoperatively and at each follow-up visit. Postoperative radiographs were
      evaluated for graft integrity and Kellgren & Lawrence Grade for osteoarthritis
      severity. Complications and reoperation were assessed by chart review. Kaplan
      Meier survivorship analyses with 95% confidence intervals were performed for the
      end point of conversion to total hip arthroplasty. RESULTS: At a mean follow-up
      of 68.8 months (26-113), the mean mHHS improved significantly (P < .001) from
      48.9 (19-84) to 77.4 (35-98). Sixteen of 22 patients (72.7%) had an mHHS >=70 at
      the latest follow-up. Arthritic progression, as indicated by an increase in the
      Kellgren & Lawrence Grade, occurred in 4 of 22 hips (18.2%). Five patients
      (22.7%) underwent conversion to total hip arthroplasty. Graft survivorship was
      86.4 +/- 7.3% at 2 years, 78.5 +/- 10.0% at 5 years, and 67.3 +/- 13.5% at 9
      years. CONCLUSION: Fresh OAT may be a viable treatment option for osteochondral
      defects of the femoral head in young, active patients with minimal preexisting
      joint deformity.

PMID- 29573914
TI  - Prior High Tibial Osteotomy Does Not Affect the Survival of Total Knee
      Arthroplasties: Results From the Danish Knee Arthroplasty Registry.
AB  - BACKGROUND: High tibial osteotomy (HTO) is a joint preserving treatment of
      unicompartmental osteoarthritis in the knee. In cases with insufficient or
      deteriorating clinical results patients may undergo a total knee arthroplasty
      (TKA). The influence of prior HTO on TKA survival is debated. METHODS: We
      conducted a population-based registry study comparing 1044 primary TKAs in
      patients with prior HTO to 63,763 de novo TKAs inserted from 1997 to 2015.
      Implant survival was estimated by Kaplan-Meier analysis with revision of any kind
      as endpoint. Patient and surgery characteristics, including choice of implant
      design, were compared and their influence on TKA survival was estimated by Cox
      regression. Finally, indications of revision were compared between the groups.
      RESULTS: TKA following HTO had an inferior survival with a 10-year estimated
      survival of 91% compared to 94% for de novo TKA, corresponding to a crude hazard
      ratio (HR) of 1.73 (P < .001). However, after adjustment for differences in
      gender and age this risk diminished (HR 1.19, P = .09). The choice of implant
      constraint was similar between the groups and in both groups posterior stabilized
      TKA was associated with inferior survival with an adjusted HR of 1.46 (P = .03)
      in post-HTO TKA when compared to cruciate-retaining TKA. CONCLUSION: TKA
      following HTO had a crude inferior survival when compared to TKA without prior
      surgery of any kind. The inferior survival was explainable by patient
      characteristics, defined by male gender and lower age, rather than the prior HTO.
      However, when the prior HTO resulted in the use of posterior stabilized TKA the
      survival decreased.

PMID- 29573915
TI  - Letter to the Editor on "Incidence, Risk Factors, and Clinical Implications of
      Pneumonia After Total Hip and Knee Arthroplasties".

PMID- 29573916
TI  - Position of the Hip in Yoga.
AB  - BACKGROUND: Yoga is growing in popularity as a form of exercise throughout the
      world. Orthopedic patients participate in yoga, yet little is known about the
      ranges-of-motion of the hip within various yoga poses. Orthopedic surgeons are
      unsure about what potential positions their patients are placing their hips
      during a yoga practice. The aim of this study is to quantify the degree of hip
      motion with common yoga poses. METHODS: Twenty healthy, regular practitioners of
      yoga performed 11 different yoga poses in a standardized fashion. Motion analysis
      was used to capture range-of-motion of the hip during each pose. RESULTS: Many
      yoga poses put the hip in extremes of motion. Poses such as downward dog, forward
      fold, seated twist, and pigeon stressed the hip in flexion. Warrior 1, warrior 2,
      crescent lunge, pigeon, and triangle stressed the hip in extension. Eagle and
      seated twist put the hip in higher adduction, while half moon, eagle, and
      triangle produced more hip internal rotation. CONCLUSION: Many poses were found
      to reach extremes of hip motion. This study may help guide the orthopedic surgeon
      in counseling hip arthroplasty and hip impingement patients about yoga-related
      activity. By knowing which poses potentially stress the hip in particular planes
      of motion, surgeons may better inform their patients who are returning to yoga
      after injury or surgery.

PMID- 29573917
TI  - Is There an Association Between Smoking Status and Prosthetic Joint Infection
      After Primary Total Joint Arthroplasty?
AB  - BACKGROUND: Recent reports highlighted the association between smoking and higher
      risk of postsurgical infections. The aim was to compare the incidence of
      prosthetic joint infection after primary total joint arthroplasty (TJA) according
      to smoking status. METHODS: A prospective hospital registry-based cohort study
      was performed including all primary knee and hip TJAs performed between March
      1996 and December 2013. Smoking status preoperatively was classified into never,
      former, and current smoker. Incidence rates and hazard ratios (HRs) for
      prosthetic joint infection according to smoking status were assessed within the
      first year and beyond. RESULTS: We included 8559 primary TJAs (mean age 69.5
      years), and median follow-up was 67 months. There were 5722 never, 1315 former,
      and 1522 current smokers. Incidence rates of infection within the first year for
      never, former, and current smokers were, respectively, 4.7, 10.1, and 10.9
      cases/1000 person-years, comparing ever vs never smokers, crude and adjusted HRs
      were 2.35 (95% confidence interval [CI] 1.39-3.98) and 1.8 (95% CI 1.04-3.2).
      Beyond the first year, crude and adjusted HRs were 1.37 (95% CI 0.78-2.39) and
      1.12 (95% CI 0.61-2.04). CONCLUSION: Smoking increased the infection risk about
      1.8 times after primary hip or knee TJA in both current and former smokers.
      Beyond the first year, the infection risk was similar to never smokers.

PMID- 29573918
TI  - Minimum 10-Year Outcome of One-Stage Total Hip Arthroplasty Without
      Subtrochanteric Osteotomy Using a Cementless Custom Stem for Crowe III and IV Hip
      Dislocation.
AB  - BACKGROUND: Options for total hip arthroplasty (THA) in high dislocated hips
      include subtrochanteric osteotomy (STO), high hip center positioning, and 2-stage
      surgery with progressive lowering using an external fixator before THA. We
      described the long-term results of 1-stage THA performed without STO, using a
      cementless customized stem associated if necessary with sequential tenotomies
      and/or greater trochanteric osteotomy. METHODS: Ninety-eight consecutive THA
      without STO were performed using this technique. Of those 98 hips, 26 hips with
      high dislocation (12 class III and 14 class IV according to the Crowe
      classification) were evaluated at an average follow-up of 16 (10-22) years.
      RESULTS: At the time of last follow-up, the mean Harris Hip Score was 86 points
      (37-100). The mean leg-length discrepancy was 7 +/- 5 mm (0-17). Two transient
      (7.7%) nerve palsies (1 sciatic and 1 femoral) were notified. A revision was
      required for 6 hips (23.1%). Kaplan-Meier survivorship analysis at 15 years
      regarding aseptic loosening of the femoral component was 87.5% (95% confidence
      interval, 76.5-99.1). During the same period, acetabular implant survivorship
      free from revision for aseptic loosening was 96.1% (95% confidence interval, 92.7
      99.9). CONCLUSION: The combination of intramedullary fit and extramedullary
      adaptation for offset and anteversion provided by the custom stem can avoid
      additional procedures associated to THA in high developmental dysplasia of the
      hip. The clinical function and long-term survival reported in this series is
      encouraging for THA performed in case of high hip dislocation.

PMID- 29573919
TI  - Deep Vein Thrombosis Prophylaxis: State of the Art.
AB  - The selection of a prophylaxis regimen to prevent symptomatic pulmonary embolism
      and deep vein thrombosis is a balance between efficacy and safety. The latest
      American Academy of Orthopaedic Surgeons guideline recommended that either
      chemoprophylaxis or mechanical prophylaxis be used after total joint arthroplasty
      but did not recommend specific agents. However, the latest evidence-based
      American College of Chest Physicians guideline recommended a variety of
      chemoprophylaxis and mechanical agents for a minimum of 10 to 14 days after total
      joint arthroplasty. Risk stratification is the key to the selection of the
      appropriate prophylaxis regimen for the individual patient, but the optimal risk
      stratification protocol still needs to be developed.

PMID- 29573920
TI  - Choices, Compromises, and Controversies in Total Knee and Total Hip Arthroplasty
      Modifiable Risk Factors: What You Need to Know.
AB  - BACKGROUND: Total joint arthroplasty has historically been very successful for
      most patients, yet some still incur a complication. In an era of value-based
      care, certain efforts need to be taken to optimize patients' risk profile before
      surgery to decrease the chances of readmission or surgical complication. METHODS:
      We reviewed 10 key medical conditions and lifestyle factors that surgeons should
      improve before pursuing total joint arthroplasty and provide a summary of the
      available literature to guide certain optimization thresholds. RESULTS: With
      careful attention to and the creation of a preoperative checklist, surgeons can
      identify key domains, including morbid obesity, malnutrition, diabetes, smoking,
      opioid use, poor dentition, cardiovascular disease, preoperative anemia,
      staphylococcus colonization, and psychological disorders and intervene based on
      an individual's areas of deficiencies. CONCLUSION: By following stringent
      protocols and rescheduling surgery until optimization has occurred, we can work
      to provide patients the best chance for a successful outcome with an elective hip
      or knee arthroplasty.

PMID- 29573921
TI  - The impact of daily bladder filling on small bowel dose for intensity modulated
      radiation therapy for cervical cancer.
AB  - Research demonstrates that instructing patients to have a full bladder for pelvic
      radiotherapy results in highly variable bladder volumes at daily treatment. We
      aimed to determine bladder volume variation in patients with intact cervical
      cancer treated with intensity-modulated radiotherapy (IMRT) on an empty bladder
      and estimate the difference in radiation dose to the small bowel compared to
      treating on a full bladder. We identified 29 patients treated with IMRT from 2010
      to 2013 who underwent 2 planning computed tomography (CT) scans, 1 with a full
      bladder followed by 1 with an empty bladder. Interfractional variation in bladder
      volume was measured using 782 daily cone beam computed tomography (CBCT) scans.
      To estimate dose to small bowel, radiation plans were created on both empty and
      full bladder CT scans using an automated knowledge-based planning modeling
      program. Mean bladder volume with empty bladder instructions was 67 +/- 26 cc
      compared to 91 +/- 43 cc for no bladder instructions and 154 +/- 54 cc for full
      bladder instructions (p < 0.001). There was a significant reduction in the
      absolute bladder volume variation in patients given empty bladder instructions
      compared to full bladder instructions (p < 0.05) The intraclass correlation
      coefficient showed low reliability of bladder filling across all groups (p =
      0.6). The average bowel V45 for the empty bladder plans was 188 cc, compared to
      139 cc for the full bladder plans (p < 0.05). More plans created on an empty
      bladder exceeded Quantitative Analyses of Normal Tissue Effects in the Clinic
      (QUANTEC) guidelines but this was not significant (31% vs 14%, p = 0.12).
      Reliability of bladder volume at the time of radiation treatment is low,
      regardless of bladder filling instructions, although an empty bladder reduces
      absolute variation in bladder volume. Radiation planning on an empty bladder
      predicts a larger volume of small bowel receiving 45 Gy compared to a full
      bladder, although bowel dose on average is still within QUANTEC guidelines (V45 <
      195 cc).

PMID- 29573922
TI  - Monaco treatment planning system tools and optimization processes.
AB  - The Monaco treatment planning system combines Monte Carlo dose calculation
      accuracy with robust optimization tools to provide high-quality radiotherapy
      treatment plans for three-dimensional conformal radiotherapy (3D CRT), intensity
      modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT),
      stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT).
      Recent technology advances have allowed for fast calculation speeds, which allow
      clinicians and patients to benefit from the accuracy of the Monte Carlo algorithm
      while reducing overall planning time. A collection of biological and physical
      dose-based planning tools and templates simplify the planning process and allow
      for consistent results across organizations. At the same time, multicriteria
      optimization (MCO) ensures critical organs are spared to the greatest possible
      degree while maintaining target coverage. Monaco encompasses a full suite of
      treatment modalities, including conventional radiotherapy and particle therapy,
      and is paving the way for real-time adaptive treatments with developments in
      magnetic resonance (MR)-guided radiation therapy.

PMID- 29573923
TI  - A comprehensive evaluation of angular range and separation on image quality,
      image registration, and imaging dose for cone beam computed tomography in
      radiotherapy.
AB  - We aimed to comprehensively evaluate the quality, dose, and registration of cone
      beam computed tomography (CBCT) images acquired with different angular range
      (theta) and angular separation (Deltatheta). Elekta XVI volumetric imaging system
      was used in this study. CBCT images of a Catphan 503 phantom were reconstructed
      with projections that were acquired under 17 * 8 different combinations of theta
      (200 degrees  to 360 degrees ) and Deltatheta (0.27 degrees  to 3.24 degrees ).
      The evaluation indices were contrast-to-noise ratio (CNR), spatial resolution
      (modulation transfer function [MTF50%]), uniformity, and registration accuracy.
      The weighted computed tomography dose index (CTDIw) of CTDI Head dosimetry
      phantom was measured for estimating radiation exposure. CNR changed little from
      theta = 200 degrees  to 260 degrees , but increased by ~ 2.0 times from theta =
      260 degrees  to 360 degrees . CNR also increased by ~ 2.5 times from Deltatheta =
      2.16 degrees  to 0.27 degrees . MTF50% increased with Deltatheta being decreased,
      but had no dependence on theta. Image uniformity became better when theta was
      smaller or larger than 260 degrees , but there was no correlation with
      Deltatheta. Registration of the overall body had a maximum error of 0.3 mm. The
      error of low-contrast objects' registration could reach as much as 1.3 mm. CTDIw
      showed a linear dependence on theta and 1/Deltatheta. Although the imaging dose
      is reduced with theta being decreased or Deltatheta being increased, the image
      quality may be degraded. Accuracy of image registration of a rigid body can be
      achieved; however, low-contrast objects' registration using images with inferior
      quality will introduce unacceptable errors for clinical use. Further, the
      benefits and extra dose received by the patients should be balanced, and scan
      protocols with theta between 210 degrees  and 260 degrees  or Deltatheta smaller
      than 0.54 degrees  should not be recommended.

PMID- 29573924
TI  - Characterization of heavy metals and PCDD/Fs from water-washing pretreatment and
      a cement kiln co-processing municipal solid waste incinerator fly ash.
AB  - A disposal method for fly ash from a municipal solid waste incinerator (MSWI-FA)
      that involved a water washing pretreatment and co-processing in a cement kiln was
      tested. The mass flows of toxic heavy metals (HMs), including volatile HM (Hg),
      semi-volatile HMs (Pb, Cd, Tl, and As), and low-volatility HMs, and
      polychlorinated dibenzo-p-dioxin/polychlorinated dibenzofuran (PCDD/Fs) in the
      input, intermediate, and output materials were characterized. The flue gas Hg
      concentrations from tests 0, 1, and 2, fed with 0, 3.1, and 1.7 t/h of dried
      washed FA (DWFA), were 28.60, 61.95, and 35.40 MUg N m-3, respectively. Co
      processing of DWFA did not significantly affect the metal concentration in
      clinker as most of the major input metals, with the exception of Cd, Pb, and Sb
      (which came from DWFA), were from raw materials and coal. Co-processing of DWFA
      did not influence on the release of PCDD/Fs; baseline and co-processing values
      ranged from 0.022 to 0.039 ng-TEQ/N m3, and from 0.01 to 0.031 ng-TEQ/N m3,
      respectively. The total destruction efficiency for PCDD/Fs in MSWI fly was 82.6%.
      This technology seems to be an environmentally sound option for the disposal of
      MSWI-FA.

PMID- 29573925
TI  - Use of solid phosphorus fractionation data to evaluate phosphorus release from
      waste activated sludge.
AB  - Waste activated sludge (WAS) can become an important source of phosphorus (P). P
      speciation was examined under anaerobic conditions, with different pH (4, 6 and
      8) and temperatures (10, 20 and 35  degrees C). Aqueous P was measured and an
      extraction protocol was used to find three solid phosphorus fractions. A pH of 4
      and a temperature of 35  degrees C gave a maximum of 51% of total P solubilized
      in 22 days with 50% of total P solubilized in 7 days. Batch tests indicate that
      little pH depression is needed to release non-apatite inorganic P (including
      microbial polyphosphate), while a pH of 4 rather than 6 will release more apatite
      inorganic P, and that organic P is relatively more difficult to release from WAS.
      Fractionation analysis of P in WAS can aid in design of more efficient methods
      for P recovery from WAS.

PMID- 29573926
TI  - Effect of the recirculation of a reverse osmosis concentrate on leachate
      generation: A case study in an Italian landfill.
AB  - "Fossetto" landfill has been operating in the municipality of Monsummano Terme
      (Pistoia Province, Italy) since 1988; the authorized volume for landfilling is
      about 1,000,000 m3; at the moment the plant is being mainly used to dispose of
      mechanically and biologically treated residual municipal solid waste. Since
      September 2006, an in-situ reverse osmosis leachate treatment plant has been
      operating to treat leachate. The treated water is being discharged into a small
      nearby stream while the concentrated leachate is being recirculated back into the
      landfill body following Italian Regulations and an authorization from the local
      authority (Pistoia Province). This paper presents monitoring results on leachate
      generation rates and composition for the past fifteen years. A moderate increase
      of the concentration of some of the monitored parameters occurred (e.g. ammonium,
      chlorides) and a decrease for most heavy metals. The increase of concentrations
      for Cl- and NH4+ was more evident in the leachate coming from the wells closer to
      reinjection area. However, the change in leachate composition did not affect the
      quality of the effluent from the leachate treatment plant. The annual volume of
      the generated leachate increased significantly right after the recirculation
      started.

PMID- 29573927
TI  - Stressing the Cardiopulmonary Vascular System: The Role of Echocardiography.
AB  - The cardiopulmonary vascular system represents a key determinant of prognosis in
      several cardiorespiratory diseases. Although right heart catheterization is
      considered the gold standard for assessing pulmonary hemodynamics, a
      comprehensive noninvasive evaluation including left and right ventricular reserve
      and function and cardiopulmonary interactions remains highly attractive. Stress
      echocardiography is crucial in the evaluation of many cardiac conditions,
      typically coronary artery disease but also heart failure and valvular heart
      disease. In stress echocardiographic applications beyond coronary artery disease,
      the assessment of the cardiopulmonary vascular system is a cornerstone. The
      possibility of coupling the left and right ventricles with the pulmonary circuit
      during stress can provide significant insight into cardiopulmonary physiology in
      healthy and diseased subjects, can support the diagnosis of the etiology of
      pulmonary hypertension and other conditions, and can offer valuable prognostic
      information. In this state-of-the-art document, the topic of stress
      echocardiography applied to the cardiopulmonary vascular system is thoroughly
      addressed, from pathophysiology to different stress modalities and
      echocardiographic parameters, from clinical applications to limitations and
      future directions.

PMID- 29573928
TI  - Left-Sided Atrial Septal Pouch is a Risk Factor for Cryptogenic Stroke.
AB  - BACKGROUND: The atrial septal pouch is an anatomic variant of the interatrial
      septum. The morphology of the left-sided septal pouch (LSSP) may favor blood
      stasis and predispose to thromboembolic events. The aim of this study was to
      determine the association between LSSP presence and cryptogenic stroke. METHODS:
      A total of 126 consecutive patients with cryptogenic stroke and 137 age-matched
      control patients without stroke were analyzed retrospectively. The presence and
      dimensions of LSSPs were assessed using transesophageal echocardiography.
      RESULTS: LSSP was present in 55.6% of patients with cryptogenic stroke and in
      40.9% of those without stroke (P = .02). In univariate analysis, patients with
      LSSP were more likely to have cryptogenic stroke (odds ratio, 1.81; 95% CI, 1.11
      2.95; P = .02). After adjusting for other risk factors using multiple logistic
      regression, the presence of an LSSP was found to be associated with an increased
      risk for cryptogenic stroke (odds ratio, 2.02; 95% CI, 1.19-3.41; P = .01). There
      were no statistically significant differences in size of the LSSP between
      patients with and those without stroke (P > .05). CONCLUSIONS: There is an
      association between the presence of an LSSP and an increased risk for cryptogenic
      stroke. More attention should be paid to clinical evaluations of LSSPs.

PMID- 29573929
TI  - Standardized Goal-Directed Valsalva Maneuver for Assessment of Inducible Left
      Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: The Valsalva maneuver is widely used to provoke left ventricular
      outflow tract obstruction in hypertrophic cardiomyopathy (HCM). Whereas early
      experiments used a standardized, goal-directed approach by maintaining an
      intraoral pressure >40 mm Hg for >10 sec, current practice depends on patients'
      understanding and effort. The aim of this study was to evaluate the clinical
      effectiveness of the goal-directed Valsalva maneuver (GDV) in HCM as a method to
      provoke left ventricular outflow tract obstruction. METHODS: In this prospective
      study, patients blew into a syringe barrel connected to a manometer with rubber
      tubing and maintained an intraoral pressure of >40 mm Hg for >10 sec (GDV). Using
      Doppler echocardiography, peak left ventricular outflow tract gradient (pLVOTG)
      was measured at rest and using the provocative maneuvers of the self-directed
      Valsalva maneuver (SDV), GDV, and exercise. RESULTS: A total of 52 patients were
      included. Mean pLVOTG with GDV was higher compared with SDV (48 vs 38 mm Hg, P =
      .001, n = 52) and was similar to exercise (GDV, 52 mm Hg; exercise, 58 mm Hg; P =
      .42; n = 43). Reclassification to obstructive HCM (pLVOTG >= 30 mm Hg) with GDV
      was significantly higher than with SDV (38% vs 16.6%, P = .016) and comparable
      with exercise (50%, P = .51). Reclassification to severe obstruction (pLVOTG >=
      50 mm Hg) was higher with GDV compared with SDV (28.3% vs 13.5%, P = .045) and
      was similar to exercise (29.7%). Furthermore, GDV identified two patients with
      occult severe obstruction in isolation. CONCLUSIONS: GDV is an objective,
      practical, and effective physiologic method of provoking left ventricular outflow
      tract obstruction. It can significantly alter patient management by reclassifying
      disease severity and should be incorporated in the routine clinical evaluation of
      patients with HCM.

PMID- 29573930
TI  - Is It Time to Revise the Guidelines and Recommendations for Digital
      Echocardiography?

PMID- 29573931
TI  - Acromioclavicular and Coracoclavicular Ligament Reconstruction for
      Acromioclavicular Joint Instability: A Systematic Review of Clinical and
      Radiographic Outcomes.
AB  - PURPOSE: To perform a systematic review of the available literature on clinical
      and radiographic outcomes after surgical treatment for acromioclavicular (AC)
      joint instability. METHODS: A systematic review was performed according to PRISMA
      guidelines. Inclusion criteria were AC joint and coracoclavicular (CC) ligament
      reconstruction outcomes, English language, human studies, more than 10 patients
      in the study and a 2-year minimum follow-up. Exclusion criteria were animal
      studies, cadaveric studies, clinical studies without reported follow-up period or
      patient-reported outcomes, clinical studies of nonoperative treatment, AC
      reconstructions with concurrent lateral clavicle fracture, editorial articles,
      abstracts, presentations, reviews, case reports, and surveys. RESULTS: The
      systematic review identified 34 studies (939 patients) after inclusion and
      exclusion criteria application. Postoperative American Shoulder and Elbow
      Surgeons (ASES) scores ranged from 93.8 to 96, 81.8 to 97.8, and 88.1 for free
      tendon graft, suspensory devices, and modified Weaver-Dunn techniques,
      respectively. Postoperative Constant scores were 76.4 to 96.0, 82.6 to 97.8, 85.9
      to 97.0, 81 to 96 and 83.0 to 94.6 for free tendon graft, suspensory devices,
      synthetic ligament devices, modified Weaver-Dunn, and hook plate/K-wires
      techniques, respectively. All treatment modalities improved patient outcomes;
      however, hook plates and K-wires had the highest rate of complications (26.3%).
      Unplanned reoperation rates were 1.2%, 2.8%, 0.9%, 5.4%, and 2.6% in free tendon
      graft, suspensory devices, synthetic ligament devices, modified Weaver-Dunn, and
      hook plate/K-wires techniques, respectively. CONCLUSIONS: Comparable subjective
      outcomes after surgical treatment of AC joint instability was reported for all
      modalities, with relatively low unplanned reoperation rates. Treatment with hook
      plate/K-wires was associated with the highest complication rates, and modified
      Weaver-Dunn had the highest unplanned reoperation rates. LEVEL OF EVIDENCE: Level
      IV, systematic review of Level I-IV studies.

PMID- 29573932
TI  - Radiologic and Histologic Evaluation of Proximal Bicep Pathology in Patients With
      Chronic Biceps Tendinopathy Undergoing Open Subpectoral Biceps Tenodesis.
AB  - PURPOSE: To correlate preoperative magnetic resonance imaging (MRI) and
      intraoperative anatomic findings within the proximal long head biceps tendon to
      histologic evaluation of 3 separate zones of the tendon in patients with chronic
      biceps tendinopathy. METHODS: Sixteen patients with chronic biceps tendinopathy
      were treated with open subpectoral biceps tenodesis. Preoperative MRI tendon
      grading was as follows: normal tendon, increased signal, tendon splitting,
      incomplete/complete tear. The removed portion of the biceps tendon was split into
      3 segments: zone 1, 0-3.5 cm from the labral insertion; zone 2, 3.5-6.5 cm; and
      zone 3, 6.5-9 cm, and was histologically evaluated using the Bonar score.
      Tenosynovium adjacent to the tendon was assessed histologically using the
      Osteoarthritis Research Society International score. CD31, CD3, and CD79a
      immunohistochemistries were conducted to determine vascularization, T-cell
      infiltrates, and B-cell infiltrates, respectively. Analysis of variance and
      Pearson correlations were performed for statistical analysis. RESULTS:
      Preoperative MRI showed no significant differences in tendon appearance between
      zones 1-3. Intraoperative findings included nonspecific degenerative SLAP tears
      or mild/moderate biceps tenosynovitis in all cases. Significantly (P < .001)
      higher Bonar scores were noted for tendon in zones 1 (7.9 +/- 1.8) and 2 (7.3 +/-
      1.5) compared with zone 3 (5.0 +/- 1.1). Cell morphology scores in zone 1 (1.9 +/
      0.4) and zone 2 (1.5 +/- 0.6) were significantly higher than that in zone 3 (0.8
      +/- 0.3) (P < .05). Inflammatory tenosynovium showed weak correlation with tendon
      changes in zone 1 (r = 0.08), zone 2 (r = 0.03), or zone 3 (r = 0.1).
      CONCLUSIONS: In patients with chronic long head biceps tendinopathy who underwent
      open subpectoral tenodesis, MRI and intraoperative assessment did not show
      significant structural abnormalities within the tendon despite significant
      histopathologic changes. Severity of tendon histopathology was more pronounced in
      the proximal and mid-portions of the tendon. CLINICAL RELEVANCE: Proximal versus
      distal biceps tenodesis is a subject of frequent debate. This study contributes
      to the ongoing evaluation of the characteristics of the proximal biceps in this
      type of pathologic condition.

PMID- 29573933
TI  - Capsulodesis Versus Bone Trough Technique in Lateral Meniscal Allograft
      Transplantation: Graft Extrusion and Functional Results.
AB  - PURPOSE: To compare the radiographic results (in terms of graft extrusion) and
      the functional results of lateral meniscus allograft transplantations (MAT)
      performed with a bony fixation technique or with a soft tissue fixation technique
      after capsulodesis. METHODS: A prospective series of 29 consecutive lateral MAT
      was analyzed. The inclusion criterion for MAT was lateral joint line pain due to
      a previous meniscectomy. Malalignment, patients who had an Ahlback grade greater
      than II, and patients with a body mass index over 30 were considered as the
      exclusion criterion to prevent confounding results. Fifteen of the grafts were
      fixed with a bony fixation technique (group A). The remaining 14 cases (group B)
      were fixed with sutures through bone tunnels after lateral capsular fixation
      (capsulodesis). All patients were studied with magnetic resonance imaging to
      determine the degree of meniscal extrusion at an average of 18 months of surgery
      (range, 12-48 months). Meniscal extrusion was measured on coronal magnetic
      resonance imaging. To standardize the results, the percentage of meniscus
      extruded for each group was also calculated and compared. The functional results
      were analyzed by means of standard knee scores (Lysholm, Tegner, and visual
      analog scale). RESULTS: If we consider the first 4 cases of group B as the
      learning curve of the new technique, we observe that group A had 8 cases (53.3%)
      of major extrusion, whereas group B had 1 case (7.1%) (P = .02). When comparing
      the degree of meniscal extrusion with the type of fixation employed, an even
      lower percentage of extruded menisci was found in group B (P = .01). The final
      follow-up Lysholm score in group A was 94.33 +/- 5.96 (P < .001) and 91.43 +/-
      6.19 (P < .001) in group B. The median follow-up Tegner score significantly
      improved from 4 (range, 2-5) to 7 (range, 6-9) in group A (P < .001) and from 4
      (range, 3-5) to 7 (range, 6-8) in group B (P < .001). The average visual analog
      scale score dropped down 5.87 and 7.29 points in groups A and B, respectively (P
      < .001). The Knee Injury and Osteoarthritis Outcome Score improved from 51.98 +/-
      2.84 to 90.88 +/- 7.53 in group A (P < .001) and from 50.44 +/- 2.32 to 92.01 +/-
      6.71 in group B (P < .001). Patient satisfaction with regard to the procedure
      stood at a mean of 3.6 +/- 0.2 points out of a maximum of 4 in group A and 3.8 +/
      0.4 in group B. There were no complications in this series. CONCLUSIONS: The
      capsulodesis technique in lateral MAT proved not to be statistically different at
      decreasing the degree of meniscal extrusion with respect to the bone-bridge
      fixation. If the first 4 cases using the new capsulodesis technique had not
      included in the results, the capsulodesis technique would have effectively
      presented better results relative to the degree of meniscal extrusion compared
      with the bone-bridge fixation technique. In addition, the functional results were
      similar. LEVEL OF EVIDENCE: Level II, prospective comparative study.

PMID- 29573934
TI  - Influence of Muscle Fatty Degeneration on Functional Outcomes After Endoscopic
      Gluteus Medius Repair.
AB  - PURPOSE: To report the early outcomes of endoscopic repair of tears of the
      gluteus medius tendon and to determine whether the fatty degeneration had an
      influence on clinical results. METHODS: Between October 2012 and June 2014, data
      were prospectively collected and retrospectively reviewed for all patients who
      underwent endoscopic gluteus medius repair. Patients were assessed pre- and
      postoperatively using the modified Harris hip score, the nonarthritic hip score,
      and visual analog scale for pain. The gluteus minimus and the 3 distinct parts of
      the gluteus medius (anterior, middle, and posterior) were assigned a grade of
      fatty degeneration on preoperative magnetic resonance imaging scans. RESULTS:
      Twenty-two hips (in 20 patients) were assessed with the mean follow-up of 31.7
      months (range: 24 to 47 months). There were 15 partial-thickness and 7 full
      thickness tears. No patient was lost to follow-up. The mean age at the time of
      surgery was 66 years (range: 45 to 82 years). Of the 20 magnetic resonance
      imaging-assessed hips included in the study, 14 had fatty degeneration of the
      gluteus medius (partial-thickness tears: n = 8, full-thickness tears: n = 6). The
      mean gluteus medius fatty degeneration index was 1.57 (range: 0.33 to 3.33).
      Postoperative improvement was seen in modified Harris hip score (33.7 points vs
      80.2 points, P = .0001), nonarthritic hip score (47.7 points vs 76.8 points, P =
      .0001), and in the visual analog scale for pain (7.2 vs 3.2, P < .05). Increasing
      preoperative fatty degeneration index of the gluteus medius correlated with
      decreased postoperative functional hip score values (regression coefficient,
      0.5839; P < .0001). Tear characteristics (partial or full-thickness) did not
      correlate with fatty degeneration or muscular atrophy and did not affect
      postoperative outcomes. CONCLUSIONS: Endoscopic surgical repair can be an
      effective treatment of gluteus medius tears in the short term. Fatty degeneration
      of the gluteus medius and minimus has a negative impact on clinical outcomes of
      endoscopic gluteus medius repair. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series (no control group).

PMID- 29573935
TI  - Diagnostic Radiology Resident Recruitment Part II: Advice to Applicants From Vice
      Chairs for Education.
AB  - Applicants to diagnostic radiology residencies often obtain advice regarding the
      process, typically from local individuals. Materials available on the Internet
      contribute to this process as well. We are a group of current and former
      Diagnostic Radiology Residency Program Directors and current Vice Chairs for
      Education who commonly advise medical students, including regarding radiology as
      a career. This work is meant to provide a "plain talk" resource for those
      considering a career in radiology via a radiology residency, written from the
      point of view of an advisor with lots of experience.

PMID- 29573936
TI  - Accuracy of Dual-Energy Virtual Monochromatic CT Numbers: Comparison between the
      Single-Source Projection-Based and Dual-Source Image-Based Methods.
AB  - RATIONALE AND OBJECTIVES: To investigate the accuracy of dual-energy virtual
      monochromatic computed tomography (CT) numbers obtained by two typical hardware
      and software implementations: the single-source projection-based method and the
      dual-source image-based method. MATERIALS AND METHODS: A phantom with different
      tissue equivalent inserts was scanned with both single-source and dual-source
      scanners. A fast kVp-switching feature was used on the single-source scanner,
      whereas a tin filter was used on the dual-source scanner. Virtual monochromatic
      CT images of the phantom at energy levels of 60, 100, and 140 keV were obtained
      by both projection-based (on the single-source scanner) and image-based (on the
      dual-source scanner) methods. The accuracy of virtual monochromatic CT numbers
      for all inserts was assessed by comparing measured values to their corresponding
      true values. Linear regression analysis was performed to evaluate the dependency
      of measured CT numbers on tissue attenuation, method, and their interaction.
      RESULTS: Root mean square values of systematic error over all inserts at 60, 100,
      and 140 keV were approximately 53, 21, and 29 Hounsfield unit (HU) with the
      single-source projection-based method, and 46, 7, and 6 HU with the dual-source
      image-based method, respectively. Linear regression analysis revealed that the
      interaction between the attenuation and the method had a statistically
      significant effect on the measured CT numbers at 100 and 140 keV. CONCLUSIONS:
      There were attenuation-, method-, and energy level-dependent systematic errors in
      the measured virtual monochromatic CT numbers. CT number reproducibility was
      comparable between the two scanners, and CT numbers had better accuracy with the
      dual-source image-based method at 100 and 140 keV.

PMID- 29573937
TI  - Comparison of Local Injection of Fresh Frozen Plasma to Traditional Methods of
      Hemostasis in Minimally Invasive Procedures.
AB  - RATIONALE AND OBJECTIVES: To evaluate different techniques for reducing
      hemorrhagic complications in coagulopathic patients with elevated international
      normalized ratio having an image-guided percutaneous invasive procedure;
      techniques included systemic transfusion of fresh frozen plasma (FFP), local
      injection of FFP, percutaneous injection of gelatin sponge, and percutaneous
      placements of angiographic coils. MATERIALS AND METHODS: Retrospective review of
      232 consecutive patients with known coagulopathy undergoing image-guided
      minimally invasive procedures were selected. Ninety-one patients had local FFP
      injected, 40 patients underwent local synthetic gelatin injection, 16 patients
      had percutaneous coil embolization, and 85 patients received systemic FFP. The
      number of bleeds, complications related to bleeds, and systemic complications
      were recorded. A 30 cc threshold was used to delineate significant bleeding.
      RESULTS: No patients experienced clinically significant or insignificant bleeding
      with local FFP injection (P value <.05). Other local hemostatic methods (Gelfoam,
      systemic FFP, and coil embolization) were associated with higher levels of
      bleeding (12.5%, 17.1%, 37.5%, respectively) and complications (7.5%, 31.4%,
      37.5%, respectively). Systemic FFP infusion was associated with respiratory,
      infectious, and mortal complications. CONCLUSIONS: Local injection of blood
      products provides a safe and efficacious hemostatic agent to reduce the incidence
      of postprocedural bleeding. The technique is associated with lower rates of
      bleeding and systemic complications when compared to other local and systemic
      techniques. Further randomized prospective studies with a larger patient cohort
      need to be performed to corroborate these initial findings.

PMID- 29573938
TI  - Teaching Radiology Trainees From the Perspective of a Millennial.
AB  - The millennial generation consists of today's medical students, radiology
      residents, fellows, and junior staff. Millennials' comfort with immersive
      technology, high expectations for success, and desire for constant feedback
      differentiate them from previous generations. Drawing from an author's
      experiences through radiology residency and fellowship as a millennial, from
      published literature, and from the mentorship of a long-time radiology educator,
      this article explores educational strategies that embrace these characteristics
      to engage today's youngest generation both in and out of the reading room.

PMID- 29573940
TI  - Is there any interest in a new BRAF-MEK inhibitor combination in melanoma?

PMID- 29573939
TI  - Differentiation of Benign and Malignant Thyroid Nodules by Using Comb-push
      Ultrasound Shear Elastography: A Preliminary Two-plane View Study.
AB  - RATIONALE AND OBJECTIVES: Low specificity of traditional ultrasound in
      differentiating benign from malignant thyroid nodules leads to a great number of
      unnecessary (ie, benign) fine-needle aspiration biopsies that causes a
      significant financial and physical burden to the patients. Ultrasound shear wave
      elastography is a technology capable of providing additional information related
      to the stiffness of tissues. In this study, quantitative stiffness values
      acquired by ultrasound shear wave elastography in two different imaging planes
      were evaluated for the prediction of malignancy in thyroid nodules. In addition,
      the association of elasticity measurements with sonographic characteristics of
      thyroid gland and nodules is presented. MATERIALS AND METHODS: A total number of
      155 patients (106 female and 49 male) (average age 57.48 +/- 14.44 years) with
      173 thyroid nodules (average size 24.89 +/- 15.41 mm, range 5-68 mm) scheduled
      for fine-needle aspiration biopsy were recruited from March 2015 to May 2017.
      Comb-push shear elastography imaging was performed at longitudinal and transverse
      anatomic planes. Mean (Emean) and maximum (Emax) elasticity values were obtained.
      RESULTS: Measurements at longitudinal view were statistically significantly
      higher than measurements at transverse view. Nodules with calcifications were
      associated with increased elasticity, and nodules with a vascular component or
      within an enlarged thyroid gland (goiter) were associated with a lower elasticity
      value. Receiver operating characteristic curve analysis was performed for Emean
      and Emax at each imaging plane and for the average of both planes. Sensitivity of
      95.45%, specificity of 86.61%, 0.58 positive predictive value, and 0.99 negative
      predictive value were achieved by the average of the two planes for each Emean
      and Emax parameters, with area under the curve of 92% and 93%, and a cutoff value
      of 49.09 kPa and 105.61 kPa, respectively. CONCLUSIONS: The elastic properties of
      thyroid nodules showed promise to be a good discriminator between malignant and
      benign nodules (P < .0001). However, probe orientation and internal features such
      as calcifications, vascular component, and goiter may influence the final
      elastography measurements. A larger number of malignant nodules need to be
      studied to further validate our results.

PMID- 29573941
TI  - Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with
      BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3
      trial.
AB  - BACKGROUND: Combined BRAF-MEK inhibitor therapy is the standard of care for
      BRAFV600-mutant advanced melanoma. We investigated encorafenib, a BRAF inhibitor
      with unique target-binding properties, alone or in combination with the MEK
      inhibitor binimetinib, versus vemurafenib in patients with advanced BRAFV600
      mutant melanoma. METHODS: COLUMBUS was conducted as a two-part, randomised, open
      label phase 3 study at 162 hospitals in 28 countries. Eligible patients were aged
      18 years or older and had histologically confirmed locally advanced (American
      Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV), unresectable or
      metastatic cutaneous melanoma, or unknown primary melanoma; a BRAFV600E or
      BRAFV600K mutation; an Eastern Cooperative Oncology Group (ECOG) performance
      status of 0 or 1; and were treatment naive or had progressed on or after previous
      first-line immunotherapy. In part 1 of the study, patients were randomly assigned
      (1:1:1) via interactive response technology to receive either oral encorafenib
      450 mg once daily plus oral binimetinib 45 mg twice daily (encorafenib plus
      binimetinib group), oral encorafenib 300 mg once daily (encorafenib group), or
      oral vemurafenib 960 mg twice daily (vemurafenib group). The primary endpoint was
      progression-free survival by blinded independent central review for encorafenib
      plus binimetinib versus vemurafenib. Efficacy analyses were by intention-to
      treat. Safety was analysed in patients who received at least one dose of study
      drug and one postbaseline safety assessment. The results of part 2 will be
      published separately. This study is registered with ClinicalTrials.gov, number
      NCT01909453, and EudraCT, number 2013-001176-38. FINDINGS: Between Dec 30, 2013,
      and April 10, 2015, 577 of 1345 screened patients were randomly assigned to
      either the encorafenib plus binimetinib group (n=192), the encorafenib group
      (n=194), or the vemurafenib group (n=191). With a median follow-up of 16.6 months
      (95% CI 14.8-16.9), median progression-free survival was 14.9 months (95% CI 11.0
      18.5) in the encorafenib plus binimetinib group and 7.3 months (5.6-8.2) in the
      vemurafenib group (hazard ratio [HR] 0.54, 95% CI 0.41-0.71; two-sided p<0.0001).
      The most common grade 3-4 adverse events seen in more than 5% of patients in the
      encorafenib plus binimetinib group were increased gamma-glutamyltransferase (18
      [9%] of 192 patients), increased creatine phosphokinase (13 [7%]), and
      hypertension (11 [6%]); in the encorafenib group they were palmoplantar
      erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and
      arthralgia (18 [9%]); and in the vemurafenib group it was arthralgia (11 [6%] of
      186 patients). There were no treatment-related deaths except for one death in the
      combination group, which was considered possibly related to treatment by the
      investigator. INTERPRETATION: Encorafenib plus binimetinib and encorafenib
      monotherapy showed favourable efficacy compared with vemurafenib. Overall,
      encorafenib plus binimetinib appears to have an improved tolerability profile
      compared with encorafenib or vemurafenib. Encorafenib plus binimetinib could
      represent a new treatment option for patients with BRAF-mutant melanoma. FUNDING:
      Array BioPharma, Novartis.

PMID- 29573942
TI  - RE: Rydzewska et al. Adding abiraterone to androgen deprivation therapy in men
      with metastatic hormone-sensitive prostate cancer: A systematic review and meta
      analysis. Eur J Cancer. 2017 Oct; 84:88-101.

PMID- 29573943
TI  - Distinguishing between immune-related pneumonitis and disease progression in
      advanced Non Small Cell Lung Cancer treated with PD-1 inhibitors: Can serum
      tumour markers have a role?

PMID- 29573944
TI  - Carmen Gerlach: (Trends in Immunology 39, 167-170, 2018).

PMID- 29573945
TI  - Quantifying and decomposing changes in outpatient utilization at medical
      institutions with different tiers in Taiwan, 2005-2015.

PMID- 29573946
TI  - Childhood exposure to green space - A novel risk-decreasing mechanism for
      schizophrenia?
AB  - Schizophrenia risk has been linked to urbanization, but the underlying mechanism
      remains unknown. Green space is hypothesized to positively influence mental
      health and might mediate risk of schizophrenia by mitigating noise and particle
      pollution exposure, stress relief, or other unknown mechanisms. The objectives
      for this study were to determine if green space are associated with schizophrenia
      risk, and if different measures of green space associate differently with risk.
      We used satellite data from the Landsat program to quantify green space in a new
      data set for Denmark at 30*30m resolution for the years 1985-2013. The effect of
      green space at different ages and within different distances from each person's
      place of residence on schizophrenia risk was estimated using Cox regression on a
      very large longitudinal population-based sample of the Danish population (943,027
      persons). Living at the lowest amount of green space was associated with a 1.52
      fold increased risk of developing schizophrenia compared to persons living at the
      highest level of green space. This association remained after adjusting for known
      risk factors for schizophrenia: urbanization, age, sex, and socioeconomic status.
      The strongest protective association was observed during the earliest childhood
      years and closest to place of residence. This is the first nationwide population
      based study to demonstrate a protective association between green space during
      childhood and schizophrenia risk; suggesting limited green space as a novel
      environmental risk factor for schizophrenia. This study supports findings from
      other studies highlighting positive effects of exposure to natural environments
      for human health.

PMID- 29573947
TI  - Blocking Bone Loss with l-BAIBA.
AB  - Osteocytes are cells nested within the mineralized bone matrix that play a key
      role in maintaining bone mass. New findings in Cell Reports show that beta
      aminoisobutyric acid (l-BAIBA), a metabolite secreted from muscle, promotes
      osteocyte survival under oxidative stress. This discovery reveals a novel
      mechanism linking muscle activity to skeletal health.

PMID- 29573948
TI  - AMPK: An Ambiguous Position for Atrial Fibrillation.

PMID- 29573949
TI  - Liver Dysfunction in Cardiac Surgery - What Causes It and Is There Anything We
      Can Do?

PMID- 29573950
TI  - Abdominal Gunshot Causing Ventricular Septal Injury Without Perforation into the
      Pericardium.

PMID- 29573951
TI  - Pro: Mechanical Ventilation Should Be Continued During Cardiopulmonary Bypass.

PMID- 29573952
TI  - A Comprehensive Review of Transesophageal Echocardiography During Orthotopic
      Liver Transplantation.
AB  - Orthotopic liver transplantation (OLT) is characterized by significant
      hemodynamic disturbances and anesthetic challenges. Intraoperative
      transesophageal echocardiography (TEE) can be used to guide management during
      these procedures. This review examines the role of echocardiography during OLT,
      presents common TEE findings during each phase of OLT, and discusses the benefits
      demonstrated with TEE use and the safety of TEE in this patient population.
      Finally, the authors propose an algorithm for the safe use of TEE during OLT.

PMID- 29573953
TI  - Functional Mitral Regurgitation After Aortic Valve Replacement for Aortic
      Insufficiency.

PMID- 29573954
TI  - A Simple Technique for Performing Transesophageal Echocardiography in Patients
      With Zenker's Diverticulum.

PMID- 29573955
TI  - Associations of Gastrointestinal Complications and Adverse Outcomes After Cardiac
      Surgery.

PMID- 29573956
TI  - The More, the Merrier? - Urinary Biomarkers for Prediction of Acute Kidney Injury
      After Cardiac Surgery.

PMID- 29573957
TI  - Vitamin D Improves Cardiac Function After Myocardial Infarction Through
      Modulation of Resident Cardiac Progenitor Cells.
AB  - BACKGROUND: Vitamin D has been implicated in the prevention of heart failure.
      However the underlying mechanism remains unclear. We hypothesised that these
      effects may be partially mediated by cardiac stem/progenitor cells (CPCs).
      Therefore, we examined the effects of 1,25-dihydroxyvitamin D3 (1,25D) on cell
      cycle activity and differentiation of a previously described CPC population
      called cardiac colony-forming unit fibroblasts (cCFU-Fs). METHODS: cCFU-Fs were
      isolated from adult male C57Bl/6 mouse hearts using fluorescence-activated cell
      sorting. The effect of 1,25D on cell proliferation and differentiation were was
      assessed by colony-forming and fibroblast differentiation assays. Cell cycle was
      analysed by flow cytometry. Mice with induced myocardial infarction (MI) were
      treated with 1,25D or vehicle controls and cardiac function assessed by
      echocardiography. RESULTS: 1,25D dose-dependently increased expression of vitamin
      D receptor (Vdr) and reduced large colony formation. Addition of 1,25D to cCFU-Fs
      slowed cell proliferation, promoted cell cycle arrest and decreased expression of
      pro-fibrotic factors during TGF-beta-induced fibroblast differentiation of cCFU
      Fs. After MI, 1,25D-treated mice had less left ventricular wall thinning and
      significant improvement in left ventricular systolic function compared to vehicle
      treated controls. Although no significant changes in myocardial fibrotic area and
      cardiomyocyte size were noted, treatment with 1,25D significantly inhibited
      cardiac interstitial cell proliferation after MI. CONCLUSIONS: Vitamin D
      signalling promotes cardioprotection after myocardial infarction. This may be
      through modulation of cCFU-F cell cycle. The role of 1,25D and VDR in regulating
      cardiac stem/progenitor cell function therefore warrants further investigation.

PMID- 29573958
TI  - Beta 2-Microglobulin and the Severity of Coronary Stenosis in Patients With Acute
      Coronary Syndrome.
AB  - BACKGROUND: Previous studies have shown that beta 2-microglobulin (B2M) could
      predict all-cause mortality and cardiovascular mortality in various groups of
      people. However, the relationship between B2M and severity of coronary stenosis
      in patients with acute coronary syndrome has not been established. METHODS: We
      enrolled 872 consecutive patients admitted with acute coronary syndrome in our
      study. All participants underwent coronary angiography examination or stent
      implantation after admission. The severity of coronary stenosis was assessed by
      Gensini score and the presentation of triple-vessel disease. B2M and other
      biochemical parameters were measured. All subjects were divided into quartiles of
      B2M. Multivariate linear regression and logistic regression were applied in the
      analysis. RESULTS: Gensini score and the prevalence of triple-vessel disease were
      elevated in accordance with increasing B2M quartiles (p=0.002 and p<0.001,
      respectively). Multivariate regression showed diabetes (p=0.031), high
      sensitivity C-reactive protein (hs-CRP, p=0.043) and B2M (p=0.006) were
      positively correlated with Gensini score. Logistic regression analysis revealed
      that the crude and fully adjusted odds ratios of triple-vessel disease were 2.34
      (95% CI: 1.58-3.46) and 1.97 (95% CI: 1.14-3.40) in the fourth quartile of B2M
      compared with the first quartile, respectively. However, no interactive
      relationships were found in subgroup analysis by estimated glomerular filtration
      rate or hs-CRP in the above associations, neither in the distribution of Gensini
      score (p for interaction>0.05 for both). CONCLUSION: Our data indicated that B2M
      was an independent risk factor of coronary stenosis in patients with acute
      coronary syndrome.

PMID- 29573959
TI  - Severe life-threatening asthma precipitated by a topical nonsteroidal anti
      inflammatory drug.

PMID- 29573960
TI  - Does the asthma visual analog scale relate to the Asthma Control Questionnaire?

PMID- 29573961
TI  - Impact of dosage timing of once-daily inhaled corticosteroids in asthma: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Once-daily inhaled corticosteroids (ICSs) are widely used as first
      line therapy in patients with asthma. OBJECTIVE: To compare the efficacy of ICSs
      administered once daily in the morning or evening as determined by lung function.
      METHODS: Medline, Embase, and the Cochrane Central Register were searched for
      relevant clinical trials. The primary outcome was lung function assessed as
      trough forced expiratory volume in 1 second and peak expiratory flow at end
      point. RESULTS: Eight randomized clinical trials involving 1,234 patients were
      analyzed. The total number of patients treated with once-daily ICS in the morning
      and evening was 628 and 606, respectively. Pooled estimates showed that ICS
      administered once daily in the evening resulted in mild improvements in trough
      forced expiratory volume in 1 second (mean difference 0.05 L; 95% confidence
      interval 0.01-0.09; P = .026; I2 = 22.5%) and morning peak expiratory flow (mean
      difference 13.92 L/min; 95% confidence interval 5.77-22.06; P = .001; I2 = 13%)
      at end point compared with morning dosing. The change in use of rescue medicine
      and the incidence of adverse events with once-daily ICS were not significantly
      different between the 2 dosing times. CONCLUSION: Compared with morning dosing,
      ICSs administered once daily in the evening seemed to provide some benefits in
      lung function for patients with asthma. However, because of methodologic
      limitations, further large-scale randomized clinical trials for dosing time of
      once-daily ICSs are needed.

PMID- 29573962
TI  - Natural history and management of splanchnic artery aneurysms in a single
      tertiary referral center.
AB  - OBJECTIVE: Splanchnic artery aneurysms (SAAs) are rare, and little is known about
      their natural history and management. We reviewed our single-center experience in
      managing this population of patients. METHODS: A retrospective review of the Yale
      radiologic database from January 1999 to December 2016 was performed. Only
      patients with an SAA and a computed tomography scan of the abdomen were selected
      for review. Demographics of the patients, aneurysm characteristics, management,
      postoperative complications, and follow-up data were collected. Our primary
      outcomes included aneurysm growth rate and risk of rupture in those patients
      managed nonoperatively and morbidity and mortality of those SAA patients who
      underwent operative intervention. RESULTS: There were 122 patients with 138 SAAs
      identified; 77 were male (62%), with a mean age of 66 years (range, 25-94 years).
      On computed tomography, 56 (45%) had previously diagnosed or concomitant
      aneurysms elsewhere. Of the patients managed nonoperatively, 101 patients (79%)
      had 108 SAAs; in the operative intervention group, 25 (21%) patients had 30 SAAs.
      The mean overall vessel diameter was 1.76 +/- 0.83 cm. The diameter of observed
      and operatively repaired SAAs was 1.58 +/- 0.56 cm and 2.41 +/- 1.23 cm,
      respectively (P = .00001). Mean follow-up was 50 +/- 42 months for nonoperative
      management without any adverse events related to SAA, including 10 patients with
      SAA >2.0 cm. The mean observed growth rate for SAA was 0.064 +/- 0.18 cm/y. All
      symptomatic patients who presented with severe abdominal pain (n = 11 [44%])
      underwent operative intervention. Five patients presented with a ruptured SAA
      (3.6%; range, 2.3-5.0 cm); all of them except one underwent operative
      intervention. Other indications for repair included large size in seven, rapid
      growth in two, other open abdominal surgical procedures in two, multiple
      aneurysms in one, and desire to pursue fertility treatment in one. Operative
      repair included 14 (56%) endovascular embolizations and 11 (44%) open abdominal
      operations. After endovascular embolization, two patients underwent abdominal
      operation for hemorrhage and splenectomy. Open repairs included bypasses in six,
      splenectomy in two, resection in two, and plication in one. Two patients had
      postoperative acute kidney injury that resolved and one died of multisystem organ
      failure. One bypass occluded without sequelae. On multivariable regression
      analysis, female sex (P = .02) was associated with faster growth rate, and a
      history of smoking (P = .04) was associated with slower growth rate. CONCLUSIONS:
      It seems reasonable to observe asymptomatic patients with an SAA <2.0 cm because
      of the slow growth rate (0.064 +/- 0.18 cm/y) and benign behavior. When
      intervention is needed, both open and endovascular options should be considered.

PMID- 29573963
TI  - High rate of over-staging of Barrett's neoplasia with endoscopic ultrasound:
      Systemic review and meta-analysis.
AB  - BACKGROUND: The use of endoscopic ultrasound (EUS) to stage patients with
      Barrett's esophagus (BE) with suspected neoplasia is controversial due to high
      rates of over-staging. However, this rate of over-staging has not been adequately
      investigated or quantified. AIM: To determine the rate of over-staging related
      EUS in this population. METHODS: Search included Medline, Embase, Web of Science,
      and Cochrane Central ending on 9/30/2016. The primary effect-estimate of interest
      was the false positive rate of advanced disease on EUS at the tumor level (T1a
      vs. T1b). Secondary outcomes included false detection rate, false negative rate,
      accuracy, sensitivity, and specificity. Study heterogeneity was assessed using
      the I2 and Cochrane's Q. RESULTS: Of 1872 studies, 11 met our inclusion criteria
      totaling 895 patients. Based on random effects models, the pooled FPR for
      advanced disease was 9.1% ([6.5-12.5%], p<0.001). Tests of heterogeneity showed
      no significant heterogeneity for this outcome. The pooled false negative rate was
      9.2% [95%CI: 4.7-17.3%], p<0.01. Overall, the pooled accuracy of EUS results in
      BE neoplasia patients was low at 74.6% [58.7-85.8%], p=0.004. CONCLUSIONS: The
      use of EUS in BE patients with dysplasia and early neoplasia results in a large
      proportion of patients falsely over-staged and under-staged.

PMID- 29573964
TI  - An Electronic Ecological Momentary Assessment Study to Examine the Consumption of
      High-Fat/High-Sugar Foods, Fruits/Vegetables, and Affective States Among Women.
AB  - OBJECTIVE: To examine the associations between high-fat/high-sugar foods (HFHS)
      and fruit and vegetable (FV) consumption and affective states in women. METHODS:
      The researchers used electronic ecological momentary assessment to capture HFHS
      and FV consumption in the past 2 hours (predictor) and current affective states
      (outcome) across 1 week among 202 women. Multilevel linear regression was
      conducted. Weight status was tested as a moderator. RESULTS: Consumption of FV in
      the past 2 hours was positively associated with feeling happy (P < .05). Women
      who consumed more HFHS or fewer FV than others in the study reported higher
      average sadness (both P < .05). Overweight or obese women who reported more
      frequent HFHS consumption than others had higher average stress than normal
      weight women (P < .05). CONCLUSIONS AND IMPLICATIONS: The association between
      HFHS consumption and stress might be stronger in overweight or obese than normal
      weight women. Future studies could further enhance the electronic ecological
      momentary assessment method to explore other time-varying moderators and
      mediators of food consumption and affect.

PMID- 29573965
TI  - The evolution of bladder cancer genomics: What have we learned and how can we use
      it?
AB  - BACKGROUND: With advancements in molecular biology techniques, great progress has
      been made in the understanding of urothelial carcinoma pathogenesis. OBJECTIVE:
      To examine the historic description of molecular alterations in bladder cancer
      and their evolution towards our current comprehension of the biology of the
      disease. RESULTS: Historically, a two-pathway model was described from
      histological and cytogenetic studies: low-grade papillary non-muscle invasive
      bladder cancers (NMIBC) were described to arise from epithelial hyperplasia with
      loss of chromosome 9 as an early event, whereas muscle-invasive bladder cancers
      (MIBC) were considered to develop from dysplasia, associated with genetic
      instability. Although there could be connections between the 2 pathways, NMIBC
      and MIBC were largely believed to develop secondary to different molecular
      alterations. Next-generation sequencing has allowed important insights into
      cancer biology and a better understanding of the pathways involved in bladder
      cancer pathogenesis and heterogeneity. Urothelial carcinoma has been found to
      have a high frequency of somatic mutations compared to other solid tumors,
      including several mutations in multiple signaling pathways, such as cell cycle
      regulators (TP53, RB1), RTK/RAS/RAF pathway, PI3K/AKT/mTOR pathway and TERT gene
      promoter. Epigenetic changes and mutations in chromatin remodeling genes are
      especially frequent in bladder cancer. Mutations in FGFR3 and KDM6A are more
      common in NMIBC than in MIBC, whereas mutations in TP53 and KMT2D are more common
      in MIBC, suggesting the previously hypothesized 2 different pathways, with a
      subset of tumors progressing from NMIBC to MIBC. Using comprehensive RNA
      expression profiling studies, at least 5 subtypes of bladder cancer have been
      identified, the most fundamental division being Basal/Squamous-like and Luminal.
      These subtypes have different prognoses, natural histories and responses to
      systemic treatments: Luminal subtypes are enriched with papillary histology and
      have a better prognosis, while Basal/Squamous-like subtypes are enriched with
      squamous features, are associated with advanced stage at presentation, and
      portend a worse prognosis. CONCLUSION: This new understanding of bladder cancer
      will optimistically translate into better understanding of this heterogeneous
      disease and lead to improvement in patient outcome and quality of life through
      better tailored treatments.

PMID- 29573966
TI  - Probing the functions of long non-coding RNAs by exploiting the topology of
      global association and interaction network.
AB  - Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as
      immune response, development, differentiation and gene imprinting and are
      associated with diseases and cancers. But the functions of the vast majority of
      lncRNAs are still unknown. Predicting the biological functions of lncRNAs is one
      of the key challenges in the post-genomic era. In our work, We first build a
      global network including a lncRNA similarity network, a lncRNA-protein
      association network and a protein-protein interaction network according to the
      expressions and interactions, then extract the topological feature vectors of the
      global network. Using these features, we present an SVM-based machine learning
      approach, PLNRGO, to annotate human lncRNAs. In PLNRGO, we construct a training
      data set according to the proteins with GO annotations and train a binary
      classifier for each GO term. We assess the performance of PLNRGO on our manually
      annotated lncRNA benchmark and a protein-coding gene benchmark with known
      functional annotations. As a result, the performance of our method is
      significantly better than that of other state-of-the-art methods in terms of
      maximum F-measure and coverage.

PMID- 29573967
TI  - Human challenge trials in vaccine development, Rockville, MD, USA, September 28
      30, 2017.
AB  - The International Alliance for Biological Standardization organized the second
      workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The
      objective of this meeting was to examine the use of HCT, in response to the
      continuing human suffering caused by infectious diseases, preventable by the
      development of new and improved vaccines. For this, the approach of HCT could be
      valuable, as HCT can provide key safety, tolerability, immunogenicity, and
      efficacy data, and can be used to study host-pathogen biology. HCT can generate
      these data with speed, efficiency and minimal expense, albeit not with the same
      level of robustness as clinical trials. Incorporated wisely into a clinical
      development plan, HCT can support optimization or down-selection of new vaccine
      candidates, assuring that only the worthiest candidates progress to field
      testing. HCT may also provide pivotal efficacy data in support of licensure,
      particularly when field efficacy studies are not feasible. Many aspects of HCT
      were discussed by the participants, including new and existing models,
      standardization and ethics. A consensus was achieved that HCT, if ethically
      justified and performed with careful attention to safety and informed consent,
      should be pursued to promote and accelerate vaccine development.

PMID- 29573968
TI  - Systematic review of care needs for older patients treated with anticancer drugs.
AB  - OBJECTIVE: When treated with anticancer therapies, a number of issues are raised
      for older patients such as physical needs (coping with symptoms and side-effects)
      or psychological needs. Geriatric tailored interventions addressing these needs
      may be effective in terms of improving quality of life of our patients. METHODS:
      A systematic review was performed in September 2017 in MEDLINE. All reports
      assessing older patients with cancer care needs in the context of anticancer
      systemic therapy were reviewed. RESULTS: A total of 357 articles were analyzed.
      From these, 35 studies were included in the analysis. Compared to younger
      patients, the elderly had less supportive care needs. While older patients asked
      for less information than their younger counterparts, they still requested
      information on diagnosis, seriousness of the disease, chances of cure, spread of
      the disease, recovery, courses of illness, possible consequences, treatment
      procedures, treatment options, possible side effects and how to deal with them,
      and what they could do in daily life. When taking into consideration the various
      needs as assessed by the "Supportive Care Needs Survey", physical and daily
      living were the most frequently reported needs with emphasis on nutrition, coping
      with physical symptoms, dealing with side effects of treatment, and performing
      usual physical tasks and activities. CONCLUSION: Information demand seemed
      moderate but a great deal of attention was paid to nutrition and well-being.

PMID- 29573969
TI  - Significance of stereotactic body radiotherapy in older patients with early stage
      non-small cell lung cancer.
AB  - OBJECTIVES: Our aim was to investigate long-term treatment outcomes in older
      patients with early stage non-small cell lung cancer (NSCLC) and the presence or
      absence of therapeutic benefits, using the G8 screening tool. METHODS: We
      retrospectively studied 43 older patients (median age 78 years, range 65-89
      years) with stage I lung tumors (T1 and T2 tumors in 34 and 9 patients,
      respectively), who underwent stereotactic body radiotherapy (SBRT). This study
      assessed outcomes in a cohort of patients who received geriatric assessments,
      performed between 2004 and 2011, before the start of their SBRT regimen. Any
      questions asked to patients before undergoing treatment were applied to the G8
      screening tool. RESULTS: G8 scores ranged from 8 to 16 (median, 12) in all
      patients (n = 43), while G8 scores in the T1 and T2 groups ranged from 9 to 16
      (median, 13) and 8 to 15 (median, 12), respectively. In patients with G8 scores
      <=12, the 2-year and 5-year survival rates were 56.1% and 28% respectively, while
      the rates were 94.1% and 68.4%, respectively, in patients with G8 scores >=13 (P
      = 0.0014). During long-term follow-up, 25.9% of the patients (n = 43) died of the
      primary disease, NSCLC, and 34.9% of patients died of other diseases or other
      types of cancer. CONCLUSION: SBRT may be effective, even in older adults.
      Regardless of age, SBRT improved the long-term survival of patients only with G8
      scores >=13. The G8 screening tool may aid in determining whether older patients
      with comorbidities would benefit from SBRT.

PMID- 29573970
TI  - Perceptual averaging of facial expressions requires visual awareness and
      attention.
AB  - Humans, as highly social animals, are regularly exposed to the faces of
      conspecifics-often more than one at a time. This feature of social living is
      important for understanding face perception, not just because it means that
      information from faces is available in bulk, but also because it changes the way
      individuals are perceived. For instance, when two faces are seen nearby one
      another, they tend to look like each other. This phenomenon of perceptual
      averaging is robust when both faces are seen and attended. But in everyday life,
      some faces may not receive the full benefit of attention, or they may not be
      visible at all. We evaluated whether perceptual averaging of relatively complex
      and simple information on faces, including facial expression and head
      orientation, can still occur even in these circumstances. In particular, we used
      object-substitution masking (OSM) and a dual-task designed to disrupt visual
      awareness and attention, respectively, during evaluations of briefly presented
      face pairs. Disruptions of awareness or attention eliminated averaging of facial
      expression, whereas orientation averaging persisted in spite of these challenges.
      These results demonstrate boundary conditions for the process of perceptual
      averaging. More generally, they provide insight into how the visual system
      processes multitudes of objects, both simple and complex, both with and without
      attention and awareness.

PMID- 29573971
TI  - Digenic variants of planar cell polarity genes in human neural tube defect
      patients.
AB  - Neural tube defects (NTDs) are considered to be a complex genetic disorder,
      although the identity of the genetic factors remains largely unknown. Mouse model
      studies suggest a multifactorial oligogenic pattern of inheritance for NTDs, yet
      evidence from published human studies is surprisingly absent. In the present
      study, targeted next-generation sequencing was performed to screen for DNA
      variants in the entire coding regions and intron-exon boundaries of targeted
      genes using DNA samples from 510 NTD cases. These candidate genes were PCP genes,
      including VANGL1, VANGL2, CELSR1, SCRIB, DVL2, DVL3 and PTK7. Candidate variants
      were validated using Sanger sequencing. A total of 397 single nucleotide
      variants(SNVs) were identified with a mean depth of approximately 570*. Of these
      identified SNVs, 74 were predicted to affect protein function and had a minor
      allele frequency of <0.01 or unknown. Among these 74 missense SNVs, 10 were
      identified from six NTD cases that carried two mutated genes. Of the six NTD
      cases, three spina bifida cases and one anencephaly case carried digenic variants
      in the CELSR1 and SCRIB gene; one anencephaly case carried variants in the CELSR1
      and DVL3 gene; and one spina bifida case carried variants in the PTK7 and SCRIB
      genes. Three cases that parental samples were available were confirmed to be
      compound heterozygous. None of the digenic variants were found in the 1000 genome
      database. The findings imply that genetic variation might interact in a digenic
      fashion to generate the visible NTD phenotypes and emphasize the importance of
      these genetic interactions in the development of NTDs in humans.

PMID- 29573973
TI  - Fatty Acid Oxidation Regulates the Activation of Endothelial-to-Mesenchymal
      Transition.
AB  - The molecular mechanisms underpinning the process of endothelial-to-mesenchymal
      transition (EndMT) are mostly unknown. Recently Xiong and colleagues explored for
      the first time the metabolic changes associated with the activation of the
      mesenchymal program in endothelial cells, and found that reprogramming of fatty
      acid oxidation pivotally regulates EndMT.

PMID- 29573972
TI  - Do Male Hearts Break Differently?

PMID- 29573974
TI  - The risk of neurodevelopmental disorders following Thimerosal-containing Hib
      vaccine in comparison to Thimerosal-free Hib vaccine administered from 1995 to
      1999 in the United States.
AB  - Investigators postulated that early-life exposure to organic mercury (Hg)
      significantly increases the risk of childhood neurodevelopmental disorders (NDs).
      The Vaccine Adverse Event Reporting System database was utilized to conduct a
      hypothesis testing case-control study by evaluating 3486 total adverse event
      reports reported following Haemophilus influenza type b (Hib) vaccination.
      Exposed subjects received a Thimerosal-containing formulation (HIBTITERTM, Wyeth
      Lederle), while unexposed subjects received a Thimerosal-free formulation
      (PEDVAXHIBTM, Merck). Subjects were included if they received either of these two
      Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse
      event reports with a reported outcome of autism, developmental delay, psychomotor
      delay, or NDs in general. Cases with reported outcomes of febrile convulsions,
      pyrexia, or injection site pain, all of which have no biologically plausible
      relation to Hg exposure, were also examined. Controls were defined as adverse
      event reports without any mention of the specific case outcome examined. Cases of
      reported autism (odds ratio (OR) = 2.75, p < 0.02), developmental delay (OR =
      5.39, p < 0.01), psychomotor disorder (OR = 2.38, p < 0.03), and
      neurodevelopmental disorder in general (OR = 2.70, p < 0.001) were each
      significantly more likely than their respective controls to receive Thimerosal
      containing Hib vaccine than Thimerosal-free Hib vaccine. Significant effects for
      neurodevelopmental disorder in general were observed for males (OR = 2.52, p <
      0.005), but not females when separated by gender. For the outcomes that had no
      biologically plausible relation to Hg exposure, the cases were no more likely
      than their respective controls to receive Thimerosal-containing Hib vaccine than
      Thimerosal-free Hib vaccine. This study provides suggestive evidence of an
      association between Thimerosal and neurodevelopmental outcomes and provides
      support for carrying out additional well-designed studies examining the
      association between Thimerosal-containing vaccines and a wide range of
      neurodevelopmental outcomes.

PMID- 29573975
TI  - Can a polypill one single tablet combat different cardiovascular risk factors?
AB  - Polypharmacy is defined as the use of two or more drugs simultaneously.
      Cardiovascular drugs and antihypertensives are commonly prescribed for treatment
      of cardiovascular disease (CVD), especially in elderly patients. Recent studies
      in patients with a history of CVD demonstrated that the fixed-dose combination of
      cardiovascular drugs in a polypill retain their individual efficacy, safety, and
      tolerability, thus have the potential to improve medication adherence and
      multiple risk factor control, thereby improving patient outcomes in secondary
      cardiovascular prevention. Since the initial conception of the fixed-dose
      polypill, just over a decade ago, only six large randomized trials assessing the
      efficacy and safety of this innovative concept have been completed (one is still
      ongoing). The results demonstrate that the polypill therapy significantly
      improved adherence, lowered systolic blood pressure, and low-density lipoprotein
      cholesterol, compared with usual care, in patients at high risk for CVD,
      especially among those who were undertreated at baseline. Correspondingly,
      further studies showed that the strengths of the polypill include better
      adherence, equivalent or better risk factor control, and improved quality of life
      among polypill users, as compared with usual care. However, the long-term outcome
      of the polypill on CVD events and mortality are unavailable and are currently
      being studied in clinical trials.

PMID- 29573976
TI  - The Immune System in Oncolytic Immunovirotherapy: Gospel, Schism and Heresy.

PMID- 29573977
TI  - Triple Negative Apocrine Carcinomas as a Distinct Subtype of Triple Negative
      Breast Cancer: A Case-control Study.
AB  - BACKGROUND: Invasive triple negative apocrine carcinoma (TNAC) of the breast is a
      rare type of triple negative breast cancer. Several studies reported
      significantly distinct prognosis for TNAC when compared with most of the non
      apocrine triple negative (NATN) tumors. This is a case-control study reporting
      onoutcomes from our long-term single-center experience. PATIENTS AND METHODS: We
      analyzed the clinicopathologic features of a series of 46 TNAC tumors treated in
      a 15-year period. Tumor characteristics and outcomes have been compared with a
      homogeneous control series of 43 NATN tumors treated during the same follow-up
      period. Local relapse-free survival (LRFS), distant metastases-free survival
      (DMFS), and overall survival (OS) have been evaluated. RESULTS: LRFS in the TNAC
      group was 85% and 78% at 5 and 10 years, respectively. LRFS in the NATN group was
      90% and 79% at 5 and 10 years, respectively (hazard ratio [HR], 1.14; 95%
      confidence interval [CI], 0.41-3.19; P = .80). DMFS in the TNAC group was 85% and
      85% at 5 and 10 years, respectively. DMFS in the NATN group was 85% and 75% at 5
      and 10 years, respectively (HR, 0.39; 95% CI, 0.14-1.08; P = .071). OS in the
      TNAC group was 86% and 83% at 5 and 10 years, respectively. OS in the NATN group
      was 86% and 63% at 5 and 10 years, respectively. OS was significantly better in
      the TNAC group (HR, 0.45; 95% CI, 0.20-0.99; P = .049). CONCLUSIONS: TNAC seems
      to represent a distinct group of triple negative breast cancer, characterized by
      a favorable long-term outcome when compared with NATN tumors.

PMID- 29573978
TI  - Pathogen clearance and immune adherence "revisited": Immuno-regulatory roles for
      CRIg.
AB  - Rapid elimination of microbes from the bloodstream, along with the ability to
      mount an adaptive immune response, are essential for optimal host-defense.
      Kupffer cells are strategically positioned in the liver sinusoids and efficiently
      capture circulating microbes from the hepatic artery and portal vein, thus
      preventing bacterial dissemination. In vivo and in vitro studies have probed how
      complement receptor of the immunoglobulin superfamily (CRIg), also referred to as
      Z39Ig and V-set and Ig domain-containing 4 (VSIG4), acts as a critical player in
      pathogen recognition and clearance. While recent data suggested that CRIg may
      bind bacterial cell wall components directly, the single transmembrane receptor
      is best known for its interaction with complement C3 opsonization products on the
      microbial surface. On Kupffer cells, CRIg must capture opsonized microbes against
      the shear forces of the blood flow. In vivo work reveals how immune adherence
      (IA), a process in which blood platelets or erythrocytes associate with
      circulating bacteria, plays a critical role in regulating pathogen capture by
      CRIg under flow conditions. In addition to its typical innate immune functions,
      CRIg was shown to directly and indirectly influence adaptive immune responses.
      Here, we review our current understanding of the diverse roles of CRIg in
      pathogen elimination, anti-microbial immunity and autoimmunity. In particular, we
      will explore how, through selective capturing by CRIg, an important balance is
      achieved between the immunological and clearance functions of liver and spleen.

PMID- 29573979
TI  - Incidentally detected atherosclerosis in the abdominal aorta or its major
      branches on computed tomography is highly associated with coronary heart disease
      in asymptomatic adults.
AB  - BACKGROUND: Atherosclerotic lesions in the abdominal aorta or its major branches
      are often incidentally detected on abdominal CT. However, clinical implications
      and optimal subsequent management are mostly left undetermined. METHODS:
      Consecutive, asymptomatic adults (age>=30) who underwent both abdominal CT and
      coronary computed tomography angiography as part of a self-referred health check
      up were investigated (n = 1494). RESULTS: Adjusted for cardiovascular risk
      factors, abdominal atherosclerotic lesions with stenosis<25% were associated with
      significant coronary stenosis, especially in the abdominal aorta (adjusted odds
      ratio [aOR] 3.37, 95% confidence interval [CI] 0.99-11.45) and any common iliac
      artery (aOR 2.99, 95% CI 1.43-6.26). The association was higher in
      atherosclerotic lesions with stenosis>=25%, respectively (aOR 16.39, 95% CI 4.00
      67.11; aOR 7.32, 95% CI 2.84-18.86). Furthermore, any major abdominal artery
      stenosis added predictive value to significant coronary stenosis (area under the
      receiver operating curve: 0.7598 vs. 0.8019, P < 0.001). The extent of arterial
      territory involvement was associated with the presence of significant coronary
      stenoses (P for trend <0.001). CONCLUSION: Stenotic atherosclerotic lesions in
      the abdominal aorta or its major branches incidentally detected on abdominal CT
      are relatively prevalent and carry high risk for asymptomatic coronary arterial
      disease.

PMID- 29573980
TI  - Systemic effects of deep brain stimulation on synergic control in Parkinson's
      disease.
AB  - OBJECTIVE: We explored effects of deep brain stimulation (DBS) in patients with
      Parkinson's disease (PD) on the synergic control of fingers in a multi-finger
      force production task and of muscles in a task involving vertical posture.
      METHODS: The finger task involved the four fingers of a hand producing accurate
      total force followed by a targeted quick force pulse. The postural task involved
      releasing a load from extended arms. The analysis of synergies was performed
      within the framework of the uncontrolled manifold hypothesis. RESULTS: DBS led to
      no significant changes in indices of stability during steady-state phases. In
      contrast, DBS improved indices of agility, quantified as anticipatory synergy
      adjustments that reduced stability of salient performance variables in
      preparation to their quick change. There were moderate-to-strong correlations
      between indices of both stability and agility measured in the multi-finger force
      production and multi-muscle whole-body action. CONCLUSIONS: Our results point at
      systemic changes in synergic control in PD. They show that DBS is effective in
      improving only one components of synergic control related to agility in
      performance being relatively ineffective for the stability component.
      SIGNIFICANCE: The results show systemic brain mechanisms of synergies and suggest
      differential effects of DBS on indices of stability and agility.

PMID- 29573981
TI  - Hypoventilation Therapy Alleviates Panic by Repeated Induction of Dyspnea.
AB  - BACKGROUND: Previous research has shown that hypoventilation therapy reduces
      panic symptoms in part by increasing basal partial pressure of carbon dioxide
      (PCO2) levels. We tested an additional pathway by which hypoventilation therapy
      could exert its therapeutic effects: through repeated interoceptive exposure to
      sensations of dyspnea. METHODS: A total of 35 patients with panic disorder were
      trained to perform exercises to raise their end-tidal PCO2 levels using a
      portable capnometry device. Anxiety, dyspnea, end-tidal PCO2, and respiratory
      rate were assessed during each exercise across 4 weeks of training. Mixed-model
      analysis examined whether within-exercise levels of dyspnea were predictive of
      reduction of panicogenic cognitions. RESULTS: As expected, within-exercise
      anxiety and respiratory rate decreased over time. Unexpectedly, PCO2 dropped
      significantly from the beginning to the end of exercise, with these drops
      becoming progressively smaller across weeks. Dyspnea increased and remained
      consistently above basal levels across weeks. As hypothesized, greater dyspnea
      was related to significantly lower panicogenic cognitions over time even after
      controlling for anxiety and PCO2. Additional exploratory analyses showed that
      within-exercise increases in dyspnea were related to within-exercise increases in
      anxiety but were not related to within-exercise increases in PCO2. CONCLUSIONS:
      In support of the interoceptive exposure model, we found that greater dyspnea
      during hypoventilation exercises resulted in lower panicogenic cognitions even
      after the effect of PCO2 was taken into account. The findings offer an additional
      important target in panic treatment.

PMID- 29573982
TI  - Site-directed saturation mutagenesis of polyhydroxylalkanoate synthase for
      efficient microbial production of poly[(R)-2-hydroxybutyrate].
AB  - In our previous study, artificial polyhydroxyalkanoate (PHA) poly[(R)-2
      hydroxybutyrate] [P(2HB)] was successfully biosynthesized from racemic 2HB in
      recombinant Escherichia coli using an engineered PHA synthase,
      PhaC1Ps(S325T/Q481K). Although P(2HB) has promising material properties, the low
      level of polymer production was a drawback. In this study, we performed directed
      evolution of PhaC1Ps towards enhanced P(2HB) accumulation in E. coli by site
      directed dual saturation mutagenesis at the positions 477 and 481, which was
      known for their potential in enhancing natural PHA accumulation. By using a
      screening on agar plates with Nile red, eight colonies were isolated which
      produced a greater amount of P(2HB) compared to a colony expressing the parent
      enzyme PhaC1Ps(S325T/Q481K). Among them, the cells expressing
      PhaC1Ps(S325T/S477R/Q481G) [ST/SR/QG] accumulated polymer at the highest level
      (up to 2.9-fold). As seen in PhaC1Ps(ST/SR/QG), glycine and basic amino acid
      residues (K or R) were frequently found at the two positions of the select
      mutated enzymes. The enzymatic activity of PhaC1Ps(ST/SR/QG) toward 2HB-CoA was
      approximately 3-fold higher than that of the parent enzyme. Additionally,
      expression levels of the select mutated enzymes were lower than the parent. These
      results indicated that PhaC1Ps mutagenesis at the positions 477 and 481 increased
      specific activity toward 2HB-CoA and it could result in the enhanced production
      of P(2HB).

PMID- 29573983
TI  - Isolation and identification of Penicillium chrysogenum strain Y5 and its copper
      extraction characterization from waste printed circuit boards.
AB  - Biohydrometallurgy is generally considered as a green technology for the
      recycling of industrial solid waste. In this study, an indigenous fungal strain
      named Y5 with the ability of high-yielding organic acids was isolated and applied
      in bioleaching of waste printed circuit boards (PCBs). The strain Y5 was
      identified as Penicillium chrysogenum by morphological and molecular
      identification. Meanwhile, we investigated that an optimal set of culturing
      conditions for the fungal growth and acids secretion was 15 g/L glucose with
      initial pH 5.0, temperature 25 degrees C and shaking speed 120 rpm in shaken
      flasks culture. Moreover, three bioleaching processes such as one-step, two-step
      and spent medium processes were conducted to extract copper from waste PCBs.
      Spent medium bioleaching showed higher copper extraction percentage and it was
      47% under 5%(w/v) pulp density. Transmission electron microscope (TEM)
      observation combining with energy dispersive analysis of X-rays (EDAX) showed
      that the leached metal ions did not obviously damage the hypha cells. All above
      results indicated that P.chrysogenum strain Y5 has the tolerance to metal ions,
      suggesting its potential in recycling of metals from waste PCBs in industry.

PMID- 29573984
TI  - Electromyographic analysis of balance exercises in single-leg stance using
      different instability modalities of the forefoot and rearfoot.
AB  - PURPOSE: To investigate the activity of lower extremity muscles in response to
      single-leg stance on a training device, destabilizing the forefoot while the
      rearfoot stands on a fixed plate and vice versa compared with a balance pad and
      the floor. DESIGN: Cross-sectional study. SETTING: University's laboratory.
      PARTICIPANTS: Twenty-seven healthy adults. METHODS: Surface electromyography and
      2D video analysis were used to record the activity of lower extremity muscles and
      to control sagittal knee joint angle during single-leg stance trials under one
      stable control condition and five unstable conditions. RESULTS: The majority of
      lower extremity muscles were significantly more active when the forefoot was
      destabilized while the rearfoot remained stable compared with the stable
      condition and the conditions where the forefoot was stable and the rearfoot
      unstable (p <0 .001). Mean change of knee joint angle was significantly increased
      under the conditions rearfoot stable/forefoot unstable (p = 0.001). The soleus
      muscle activation was significantly increased when balancing on the balance pad
      (p < 0.001). CONCLUSIONS: Increased activity in the majority of lower extremity
      muscles and sagittal knee joint angles indicate that destabilizing the forefoot
      while the rearfoot remains stable is the most challenging balance task. Soleus
      muscle activation increased when performing ankle plantarflexion on the soft
      balance pad.

PMID- 29573985
TI  - Accommodation and age-dependent eye model based on in vivo measurements.
AB  - PURPOSE: To develop a flexible model of the average eye that incorporates changes
      with age and accommodation in all optical parameters, including entrance pupil
      diameter, under photopic, natural, environmental conditions. METHODS: We collated
      retrospective in vivo measurements of all optical parameters, including entrance
      pupil diameter. Ray-tracing was used to calculate the wavefront aberrations of
      the eye model as a function of age, stimulus vergence and pupil diameter. These
      aberrations were used to calculate objective refraction using paraxial curvature
      matching. This was also done for several stimulus positions to calculate the
      accommodation response/stimulus curve. RESULTS: The model predicts a hyperopic
      change in distance refraction as the eye ages (+0.22D every 10 years) between 20
      and 65 years. The slope of the accommodation response/stimulus curve was 0.72 for
      a 25 years-old subject, with little change between 20 and 45 years. A trend to a
      more negative value of primary spherical aberration as the eye accommodates is
      predicted for all ages (20-50 years). When accommodation is relaxed, a slight
      increase in primary spherical aberration (0.008MUm every 10 years) between 20 and
      65 years is predicted, for an age-dependent entrance pupil diameter ranging
      between 3.58mm (20 years) and 3.05mm (65 years). Results match reasonably well
      with studies performed in real eyes, except that spherical aberration is
      systematically slightly negative as compared with the practical data.
      CONCLUSIONS: The proposed eye model is able to predict changes in objective
      refraction and accommodation response. It has the potential to be a useful design
      and testing tool for devices (e.g. intraocular lenses or contact lenses) designed
      to correct the eye's optical errors.

PMID- 29573986
TI  - Can a collaborative healthcare network improve the care of people with epilepsy?
AB  - New opportunities are now available to improve care in ways not possible
      previously. Information contained in electronic medical records can now be shared
      without identifying patients. With network collaboration, large numbers of
      medical records can be searched to identify patients most like the one whose
      complex medical situation challenges the physician. The clinical effectiveness of
      different treatment strategies can be assessed rapidly to help the clinician
      decide on the best treatment for this patient. Other capabilities from different
      components of the network can prompt the recognition of what is the best
      available option and encourage the sharing of information about programs and
      electronic tools. Difficulties related to privacy, harmonization, integration,
      and costs are expected, but these are currently being addressed successfully by
      groups of organizations led by those who recognize the benefits.

PMID- 29573987
TI  - Utilizing Coarse-Grained Modeling and Monte Carlo Simulations to Evaluate the
      Conformational Ensemble of Intrinsically Disordered Proteins and Regions.
AB  - In this study, we have used the coarse-grained model developed for the
      intrinsically disordered saliva protein (IDP) Histatin 5, on an experimental
      selection of monomeric IDPs, and we show that the model is generally applicable
      when electrostatic interactions dominate the intra-molecular interactions.
      Experimental and theoretically calculated small-angle X-ray scattering data are
      presented in the form of Kratky plots, and discussions are made with respect to
      polymer theory and the self-avoiding walk model. Furthermore, the impact of
      electrostatic interactions is shown and related to estimations of the
      conformational ensembles obtained from computer simulations and "Flexible
      meccano." Special attention is given to the form factor and how it is affected by
      the salt concentration, as well as the approximation of using the form factor
      obtained under physiological conditions to obtain the structure factor.

PMID- 29573988
TI  - Structural Insights into the Induced-fit Inhibition of Fascin by a Small-Molecule
      Inhibitor.
AB  - Tumor metastasis is responsible for ~90% of all cancer deaths. One of the key
      steps of tumor metastasis is tumor cell migration and invasion. Filopodia are
      cell surface extensions that are critical for tumor cell migration. Fascin
      protein is the main actin-bundling protein in filopodia. Small-molecule fascin
      inhibitors block tumor cell migration, invasion, and metastasis. Here we present
      the structural basis for the mechanism of action of these small-molecule fascin
      inhibitors. X-ray crystal structural analysis of a complex of fascin and a fascin
      inhibitor shows that binding of the fascin inhibitor to the hydrophobic cleft
      between the domains 1 and 2 of fascin induces a ~35o rotation of domain 1,
      leading to the distortion of both the actin-binding sites 1 and 2 on fascin.
      Furthermore, the crystal structures of an inhibitor alone indicate that the
      conformations of the small-molecule inhibitors are dynamic. Mutations of the
      inhibitor-interacting residues decrease the sensitivity of fascin to the
      inhibitors. Our studies provide structural insights into the molecular mechanism
      of fascin protein function as well as the action of small-molecule fascin
      inhibitors.

PMID- 29573990
TI  - Apoptosis and eryptosis: Striking differences on biomembrane level.
AB  - The cell plasma membrane plays an essential role in programmed cell death of
      nucleated cells (apoptosis) and erythrocytes (eryptosis), and its changes due to
      loss of transmembrane asymmetry are quite similar. However, nucleated cells
      possess the network of intracellular membranes, which are missing in
      erythrocytes. Providing comparative studies with series of molecular probes, we
      observe dramatic differences in membrane lipid order in the course of apoptosis
      and eryptosis. In contrast to nucleated cells, in which a significant drop of the
      lipid order in the plasma membrane is observed, the erythrocyte membrane retains
      the relatively high level of the lipid order. Observation in nucleated cells of
      significant differences between inner and plasma membranes and detection of
      apoptotic bodies with different organization suggest that the decrease in the
      lipid order of their plasma membrane could be at least partially explained by the
      phospholipid and/or cholesterol exchange between membranes. Such features are
      absent in erythrocytes.

PMID- 29573989
TI  - Short-interval intracortical inhibition: Comparison between conventional and
      threshold-tracking techniques.
AB  - BACKGROUND: Short-interval intracortical inhibition (SICI) is conventionally
      measured as the relative amplitude reduction of motor evoked potentials (MEPs) by
      subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus
      intensity is instead adjusted repeatedly to maintain a constant MEP and
      inhibition is measured as the relative threshold increase. T-SICI is emerging as
      a useful diagnostic test, but its relationship to conventional amplitude SICI (A
      SICI) is unclear. OBJECTIVE: To compare T-SICI and its reliability with
      conventional A-SICI measurements. METHODS: In twelve healthy volunteers (6 men,
      median age 30 years), conventional and T-SICI were recorded at conditioning
      stimuli (CS) of 50-80% resting motor threshold (RMT) and interstimulus interval
      of 2.5 ms. Measurements were repeated on the same day and at least a week later
      by a single operator. RESULTS: Across the CS range, mean group T-SICI showed a
      strong linear relationship to the mean group values measured by conventional
      technique (y = 29.7-0.3x, R2 = 0.99), but there was considerable interindividual
      variability. At CS 60-80% RMT, T-SICI had excellent intraday (intraclass
      correlation coefficient, ICC, 0.81-0.92) and adequate-to-excellent interday (ICC
      0.61-0.88) reproducibility. Conventional SICI took longer to complete (median of
      5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17
      0.42 intraday, 0.37-0.51 interday). With T-SICI, smaller sample sizes were
      calculated for equally powered interventional studies. CONCLUSION: The close
      relationship between conventional and T-SICI suggests that both techniques
      reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements
      of SICI may be able to improve reproducibility, to shorten acquisition time and
      to reduce sample sizes for interventional studies compared with the conventional
      technique.

PMID- 29573992
TI  - Corrigendum to 'Comparative study between duct to mucosa and invagination
      pancreaticojejunostomy after pancreaticoduodenectomy: A prospective randomized
      study'International Journal of Surgery 16 (2015) 1-6.

PMID- 29573991
TI  - Biophysical characterization and stabilization of detergent-solubilized
      lipoprotein N-acyl transferase from P. aeruginosa and E. coli.
AB  - Lipoproteins are important for bacterial growth and virulence and interest in
      them as targets for antibiotic development is growing. Lipoprotein N-acyl
      transferase (Lnt) catalyzes the final step in the lipoprotein posttranslational
      processing pathway. The mature lipoprotein can remain in the inner membrane or be
      trafficked to the outer membrane in the case of diderm prokaryotes. With a view
      to obtaining high-resolution crystal structures of membrane integral Lnt for use
      in drug discovery a program was undertaken to generate milligram quantities of
      stable, homogenous and functional protein. This involved screening across
      bacterial species for suitable orthologues and optimization at the level of
      protein expression, solubilization and stability. Combining biophysical and
      functional characterization, orthologous Lnt from Escherichia coli and the
      opportunistic human pathogen Pseudomonas aeruginosa was identified as suitable
      for the proposed structure determination campaign that ultimately yielded crystal
      structures. The rational approaches taken that eventually provided structure
      quality protein are presented in this report.

PMID- 29573993
TI  - Pathology of tail fan necrosis in the spiny lobster, Jasus edwardsii.
AB  - Tail fan necrosis (TFN) is the bacterial infection of the tail fan of spiny
      lobsters which leads to melanosis and erosion of the tail fan tissues. The
      condition is commonly found among spiny lobsters in aquaculture and commercial
      fisheries, and greatly reduces their commercial value. This study describes the
      pathology of TFN by examining the tail fans (telson, uropods) and internal organs
      (mid-gut, hepatopancreas, heart and gill) of 29 affected wild spiny lobsters
      (Jasus edwardsii) and 14 unaffected in New Zealand. Initial signs of TFN were
      observed around the margins of lacerations to the tail fan, with more extensive
      signs extending from these presumptive sites of initiation. The establishment of
      the condition at points of injury is consistent with the penetration of TFN
      through the cuticle and tissue layers of the affected tail fans, which is rarely
      seen in other forms of shell disease. Entry into these tissues was characterised
      initially by caseous necrosis and haemocyte accumulation, followed by the spread
      of these responses together with melanisation. Additional pathological changes to
      the tail fans included pseudomembrane formation, detachment of epidermis or
      cuticle, clotted haemolymph and fibrosis. Among internal organs, pathological
      changes were found in a total of two mid-gut, four heart and two gill samples
      from eight lobsters with TFN, while no suspected changes were found in the organs
      of lobsters without TFN. The causes of internal organ pathology associated with
      TFN in spiny lobsters warrants more detailed research.

PMID- 29573994
TI  - Vectors and reservoir hosts of covert mortality nodavirus (CMNV) in shrimp ponds.
AB  - Covert mortality nodavirus (CMNV) is the pathogen that has been identified as the
      cause of viral covert mortality disease (VCMD) in marine and brackish water
      shrimp. Recent outbreaks of this disease have resulted, and continue to result,
      in substantial production and economic losses to shrimp aquaculture producers in
      China and elsewhere. To explore potential vectors and reservoir hosts of CMNV, we
      collected fifteen species of invertebrates from shrimp ponds affected by VCMD.
      Samples were tested through the use of: reverse transcription loop-mediated
      isothermal amplification (RT-LAMP), reverse transcription nested PCR (RT-nPCR)
      followed by gene sequencing, histopathology, and in situ RNA hybridization (ISH).
      The results of RT-LAMP and RT-nPCR assay indicated that CMNV positive samples
      were identified in eleven species including brine shrimp Artemia sinica, a
      barnacle Balanus sp., the rotifer Brachionus urceus, the amphipod Corophium
      sinense Zhang, the Pacific oyster Crassostrea gigas, a hermit crab Diogenes
      edwardsii, the common clam Meretrix lusoria, a ghost crab Ocypode cordimundus,
      the hyperiid amphipod Parathemisto gaudichaudi, a fiddler crab Tubuca arcuata,
      and an unidentified gammarid amphipod. The alignment of CMNV RNA-dependent RNA
      polymerase gene sequences from eight of the species demonstrated high identities
      (97-100% in nucleotide sequence) with that from the original CMNV isolates of
      Penaeus vannamei, which suggests that these species could either be infected
      with, or acting as mechanical vectors of, CMNV. The CMNV infection in C. sinense,
      D. edwardsii, O. cordimanus Zhang, P. gaudichalldi, and T. arcuata results, to
      varying degrees, in vacuolation and necrosis of targeted tissues, as was verified
      by ISH. The infection of CMNV in these five species suggests that they might act
      as reservoir hosts of CMNV. The results indicate that the common species of
      invertebrates inhabiting shrimp ponds may constitute biological risk factors for
      CMNV outbreaks.

PMID- 29573995
TI  - Investigation of ventricular pre-excitation electrocardiographic pattern in two
      horses: clinical presentation and potential causes.
AB  - Two horses referred to the Unitat Equina, Fundacio Hospital Clinic Veterinari,
      Universitat Autonoma de Barcelona, for unrelated clinical problems, and with no
      previous history of cardiac disease exhibited an intermittent ventricular pre
      excitation electrocardiographic pattern during hospitalization. Both animals
      showed decreased plasma total and ionized magnesium concentrations, but no other
      relevant electrolyte disturbances were detected. Altered interventricular septal
      motion associated with ventricular pre-excitation beats (VPBs) was detected on M
      mode echocardiography in both horses. The likely localization of an accessory
      pathway (AP) was identified in case 2 using pulsed-wave tissue Doppler imaging in
      the left anterior paraseptal location. Decreased frequency of the VPB was
      observed with long-term magnesium supplementation and restoration of plasma
      magnesium concentrations. The presence of ventricular pre-excitation
      electrocardiographic pattern was attributed to higher sensitivity of the AP to
      hypomagnesemia in both cases.

PMID- 29573996
TI  - From melody to words: The role of sex hormones in early language development.
AB  - Contribution to Special Issue on Fast effects of steroids. Human infants are the
      most proficient of the few vocal learner species. Sharing similar principles in
      terms of the generation and modification of complex sounds, cross-vocal learner
      comparisons are a suitable strategy when it comes to better understanding the
      evolution and mechanisms of auditory-vocal learning in human infants. This
      approach will also help us to understand sex differences in relation to vocal
      development towards language, the underlying brain mechanisms thereof and sex
      specific hormonal effects. Although we are still far from being capable of
      discovering the "fast effects of steroids" in human infants, we have identified
      that peripheral hormones (blood serum) are important regulators of vocal
      behaviour towards language during a transitory hormone surge ("mini-puberty")
      that is comparable in its extent to puberty. This new area of research in human
      infants provides a promising opportunity to not only better understand early
      language acquisition from an ontogenetic and phylogenetic perspective, but to
      also identify reliable clinical risk-markers in infants for the development of
      later language disorders.

PMID- 29573997
TI  - The use of tDCS as a therapeutic option for tinnitus: a systematic review.
AB  - INTRODUCTION: Due to the subjectivity of the tinnitus diagnosis and its diverse
      etiologies, establishing an effective treatment is complex. In this context,
      transcranial direct current stimulation, a noninvasive option, is available for
      most patients and has shown good results in the treatment of other symptoms such
      as chronic pain. OBJECTIVE: To evaluate the therapeutic response of tinnitus to
      transcranial direct current stimulation. METHODS: A systematic review of the
      literature was performed using the following descriptors: tinnitus, transcranial
      direct current stimulation and randomized clinical trial. The research was
      carried out in the MEDLINE/PUBMED, Lilacs, and Scielo databases. The inclusion
      criteria were: patients over 18 years of age with no associated comorbidities,
      who had a diagnosis established by a specialist or through the application of
      previously validated scales and criteria applied by a non-specialist physician.
      RESULTS: A total of 4165 studies were found, and a total of six were selected
      after the inclusion criteria were applied, obtaining a sample of 602 patients.
      Based on the defined criteria, there was a positive response to transcranial
      direct current stimulation in 14.86% of the participants. CONCLUSION: Based on
      literature studied, there is no therapeutic response of tinnitus to transcranial
      direct current stimulation.

PMID- 29573998
TI  - Painless bilateral bullous keratopathy.
AB  - Bullous keratopathy is a pathological corneal condition that arises due to
      irreversible oedema associated with endothelial cell loss or dysfunction.
      Symptoms may vary from mild (transient blurred vision and increased glare from
      epithelial oedema) to severe (an acute and significant loss of vision associated
      with frank endothelial decompensation, and pain due to ruptured epithelial
      bullae). Possible treatments to restore vision and minimise pain include topical
      hypertonic agents, bandage contact lenses, superficial anterior corneal surgical
      procedures or penetrating full thickness or endothelial keratoplasty. This case
      report describes a rare presentation of painless, bilateral, asymmetric bullous
      keratopathy with severe vision loss in an elderly male with non-insulin dependent
      diabetes mellitus.

PMID- 29573999
TI  - Toxocara spp. infection and risk of childhood asthma: A systematic review and
      meta-analysis.
AB  - Asthma is one of the most common chronic respiratory disease worldwide, with a
      negative impact on quality of life and socio-economic status of patients. There
      are some evidences to suggest that Toxocara infection is a neglected risk factor
      for childhood asthma. We performed a systematic review and meta-analysis to
      further understanding of this relationship. Five databases include PubMed,
      Science Direct, Scopus, Web of Science (ISI), and Google scholar were searched
      (up to October 2017) to identify the relevant studies. We used random-effects
      meta-analysis model to estimate the pooled odds ratio (OR) and 95% confidence
      intervals (CI). Heterogeneity was assessed with the Q-test and I2 statistic. A
      total of 17 studies including 11 studies with case-control design (1139 patients
      and 1023 controls) and six studies with cross-sectional design (a total of 5469
      participants, 872 asthmatics, and 4597 non-asthmatics children) met the
      eligibility criteria. An increased risk for asthma was observed in children with
      Toxocara infection seropositivity (OR, 1.91; 95% CI, 1.47-2.47). In sub-group
      analysis, the pooled ORs were (OR, 2.13; 95% CI, 1.43-3.15) and (OR, 1.73; 95%
      CI, 1.23-2.44) for case-control and cross-sectional studies, respectively.
      Moreover, considering to specific IgE seropositivity, a pooled OR of 2.36 (95%
      CI, 0.93-5.98) was observed. In conclusion, this meta-analysis revealed that
      children infected with Toxocara spp. are more likely to have asthma compared to
      non-infected children. More studies (especially longitudinal studies) are needed
      to further investigate the impact of Toxocara spp. infection on the onset or
      development of asthma.

PMID- 29574000
TI  - Invasive Pomacea snails as important intermediate hosts of Angiostrongylus
      cantonensis in Laos, Cambodia and Vietnam: Implications for outbreaks of
      eosinophilic meningitis.
AB  - The rat lungworm Angiostrongylus cantonensis causes human eosinophilic meningitis
      and it is endemic in Southeast Asia, but little is known about its distribution
      in Laos, Cambodia and Vietnam. We conducted a multi-country survey for A.
      cantonensis in these countries to estimate its prevalence in snails along the
      Mekong River and the east coast of Vietnam. We identified Angiostrongylus species
      by morphological and molecular analysis. We found A. cantonensis in the invasive
      snail, Pomacea spp. The wide accessibility of Pomacea snails, along with their
      infection by A. cantonensis, indicates that this snail species could be used in
      surveillance for preventing outbreaks of eosinophilic meningitis.

PMID- 29574001
TI  - Expression and biochemical characterization of alpha-ketoglutarate decarboxylase
      from cyanobacterium Synechococcus sp. PCC7002.
AB  - alpha-Ketoglutarate decarboxylase (alpha-KGD), one member of alpha-keto acid
      decarboxylases, catalyzing non-oxidative decarboxylation of alpha-ketoglutarate
      to form succinic semialdehyde, was proposed to play critical role in completing
      tricarboxylic acid (TCA) cycle of cyanobacteria. Although the catalytic function
      of alpha-KGD from Synechococcus sp. PCC7002 was demonstrated previously, there
      was no detailed biochemical characterization of alpha-KGD from Synechococcus sp.
      PCC7002 yet. In this study, the gene encoding alpha-KGD from Synechococcus sp.
      PCC7002 was amplified and soluble expression of recombinant alpha-KGD was
      achieved by coexpressing with pTf16 chaperone plasmid in E. coli BL21 (DE3).
      Kinetic analysis showed that the activity of alpha-KGD was dependent on cofactors
      of thiamine pyrophosphate and divalent cation. Meanwhile this alpha-KGD was
      specific for alpha-ketoglutarate with respect to the decarboxylation activity
      despite of the pretty low activity of acetolactate synthase. The catalytic
      efficiency of alpha-KGD (the values of kcat and kcat/Km for alpha-ketoglutarate
      were 1.2s-1 and 6.3*103M-1s-1, respectively) might provide evidence for its
      physiological role in TCA cycle of Synechococcus sp. PCC7002.

PMID- 29574002
TI  - Treatment With JAK Inhibitors in Myelofibrosis Patients Nullifies the Prognostic
      Impact of Unfavorable Cytogenetics.
AB  - INTRODUCTION: In the era before Janus kinase (JAK) inhibitors, cytogenetic
      information was used to predict survival in myelofibrosis patients. However, the
      prognostic value of cytogenetics in the setting of JAK inhibitor therapy remains
      unknown. PATIENTS AND METHODS: We performed a retrospective analysis of 180
      patients with bone marrow biopsy-proven myelofibrosis from 3 US academic medical
      centers. We fit Cox proportional hazards models for overall survival and
      transformation-free survival on the bases of 3 factors: JAK inhibitor therapy as
      a time-dependent covariate, dichotomized cytogenetic status (favorable vs.
      unfavorable), and statistical interaction between the two. The median follow-up
      time was 37.1 months. RESULTS: Among patients treated with best available
      therapy, unfavorable cytogenetic status was associated with decreased survival
      (hazard ratio = 2.31; P = .025). At initiation of JAK inhibitor therapy,
      unfavorable cytogenetics was (nonsignificantly) associated with increased
      survival compared to favorable cytogenetics (hazard ratio = 0.292; P = .172). The
      ratio of hazard ratios was 0.126 (P = .034). These findings were similar after
      adjusting for standard clinical prognostic factors as well as when measured
      against transformation-free survival. CONCLUSION: The initiation of JAK inhibitor
      therapy appears to change the association between cytogenetics and overall
      survival. There was little difference in survival between treatment types in
      patients with favorable cytogenetics. However, the use of JAK inhibitor therapy
      among patients with unfavorable cytogenetics was not associated with worse
      survival compared to favorable cytogenetics. Our analyses suggest that initiation
      of JAK inhibitor therapy nullifies the negative prognostic implication of
      unfavorable cytogenetics established in the pre-JAK inhibitor therapy era.

PMID- 29574003
TI  - CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2
      signaling.
AB  - Beige adipocytes are thermogenic adipocytes with developmental and anatomical
      properties distinct from those of classical brown adipocytes. Recent studies have
      revealed several key molecular regulators of beige adipocyte development. CD105,
      also called endoglin, is a membrane protein composed of TGF-beta receptor
      complex. It regulates TGF-beta-family signal transduction and vascular formation
      in vivo. We report here that CD105 maintains the thermogenic gene program of
      beige adipocytes by regulating Smad2 signaling. Cd105-/- adipocyte precursors
      showed augmented Smad2 activation and decreased expression of thermogenic genes
      such as Ucp1 and Prdm16-which encodes a transcriptional regulatory protein for
      thermogenesis-after adipogenic differentiation. Smad2 signaling augmentation by
      the constitutively active form of Smad2 decreased the expression of thermogenic
      genes in beige adipocytes. Loss of thermogenic activity in Cd105-/- beige
      adipocytes was rescued by Prdm16 expression. These data reveal a novel function
      of CD105 in beige adipocytes: maintaining their thermogenic program by regulating
      Smad2 signaling.

PMID- 29574004
TI  - A multi-screening Fast qPCR approach to the identification of abortive agents in
      ruminants.
AB  - Abortion in ruminants represents an important economic concern for farmers.
      Microbial agents, such as Brucella spp., Chlamydia spp., Coxiella burnetii,
      Leptospira spp., Neospora caninum, Salmonella spp. and Toxoplasma gondii, are
      among the main infectious causes of abortion and require rapid and reliable
      diagnosis. This study describes the development of a multi-screening assay using
      Fast Real-Time PCR (Fast qPCR) that allows, in a single test, the simultaneous
      identification of the above-mentioned abortive agents. This multi-screening
      approach is characterized by a mean diagnostic sensitivity and specificity of
      100% and 97%, respectively; it has a limit of detection (LOD) ranging from 5 *
      103 to 4 * 104 genomic copies/g of tissue and a very good concordance with
      traditional end-point PCR assays used in routine diagnostic activity. The
      proposed method represents a rapid approach to the simultaneous detection of the
      main abortive agents in ruminants that allows to make an accurate diagnosis and
      to set up appropriate control measures in a short period of time.

PMID- 29574005
TI  - Prevalence and risk factors associated with chronic kidney disease in adults
      living in 3 different altitude regions in the Tibetan Plateau.
AB  - BACKGROUND: Living at high altitude may have undesirable effects on the kidney.
      We explored the chronic kidney disease (CKD) prevalence and risk factors among
      the residents living at different altitude in Tibetan Plateau. METHODS: A cross
      sectional study was carried out in 2014 to 2016 in Linzhi (2900 m altitude),
      Lhasa (3650 m) and Anduo (4700 m). Information on the cardiovascular risk factors
      was collected and blood and urine samples were measured. RESULTS: The data of
      1707 subjects aged >=35 y were analyzed. The age-standardized prevalence of CKD
      in Linzhi, Lhasa and Anduo was 27.7% (95% CI: 22.1-33.3%), 18.3% (12.7-24.0%) and
      30.4% (23.5-37.3%) in men and 37.7% (31.8-43.6%), 29.5% (24.6-34.4%) and 36.7%
      (29.0-44.4%) in women, respectively. Multivariable logistic regression showed
      that age, female gender, systolic blood pressure, fasting serum glucose, with
      primary school education or lower were associated with higher risk of CKD and
      living in Lhasa was associated with lower risk of CKD. CONCLUSION: A higher
      prevalence of CKD was found in the residents living in the Tibetan Plateau.
      However, for the highlanders living at higher altitude does not mean higher risk.
      The CKD risk factors found in this study are similar to those in other studies.

PMID- 29574006
TI  - A rapid screening of a recurrent CYP24A1 pathogenic variant opens the way to
      molecular testing for Idiopathic Infantile Hypercalcemia (IIH).
AB  - INTRODUCTION: Loss-of-function mutations in cytochrome P450 family 24 subfamily A
      member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia
      (IIH) and adult kidney stone disease. The enzyme deficiency leads to an impaired
      vitamin D catabolism pathway, resulting in a syndrome characterized by recurrent
      hypercalcemia, hypercalciuria and suppressed parathyroid hormone (PTH) levels. In
      these patients, the genetic evaluation of CYP24A1 is an important diagnostic
      tool, allowing the definitive diagnosis of IIH. METHODS: A rapid CYP24A1 gene
      testing based on High Resolution Melting Analysis (HRMA) was designed in order to
      detect the CYP24A1 c.428_430delAAG (p.Glu143del), a recurrent IIH-associated
      variant. RESULTS: HRMA method was able to identify c.428_430delAAG genotypes
      evaluating melting curve shape and melting temperature (Tm). Heterozygous samples
      exhibited a typical melting profile while homozygous samples showed a specific Tm
      shift. CONCLUSIONS: We provide evidence about application of HRMA in unambiguous
      genotyping of the CYP24A1 c.428_430delAAG variant, making this method useful in
      clinical molecular diagnostics. This approach opens the way to a helpful
      molecular analysis of CYP24A1 gene in IIH diagnosis, to an improved
      pharmacological treatment strategy and to a reduced risk of recurrent stones and
      worsening nephrocalcinosis.

PMID- 29574007
TI  - A systematic review on risk factors associated with sepsis in patients admitted
      to intensive care units.
AB  - OBJECTIVE: We sought to systematically review data on the risk factors
      influencing the incidence of sepsis in patients admitted to intensive care units
      (ICUs). REVIEW METHODS: An electronic search was undertaken in PubMed, MEDLINE,
      Scopus, and the Cochrane Library for studies reporting the risk factors of sepsis
      from the earliest available date up to December 30, 2016. RESULTS: Among the 2978
      articles, 14 studies met the inclusion criteria with a total of 56 164
      participants from nine countries. The extracted risk factors were from the
      following categories: demographic, critical care interventions, surgery-related
      factors, pre-existing comorbidities, severity of organ injury, and biomarkers and
      biochemical and molecular indicators. From demographic factors, older age and
      male gender were associated with an increased risk of sepsis among ICU-admitted
      patients. CONCLUSION: Our analysis comprehensively summarised the risk factors of
      sepsis in patients admitted to medical, surgical, neurologic, trauma, and general
      ICUs. Age, sex, and comorbidities were non-modifiable risk factors; however,
      critical care interventions and surgery-related factors were modifiable factors
      and suggest that improving the care of surgical patients and effective management
      of critical care interventions may play a key role in decreasing the development
      of sepsis in patients admitted to the ICUs.

PMID- 29574008
TI  - [Prostate cancer screening using prostate-specific antigen: The views of general
      and laboratory physicians].
AB  - INTRODUCTION: It is currently recommended to provide individualised information
      on benefit-risk balance and shared decision-making in prostate cancer screening
      using prostate-specific antigen (PSA). AIM: To determine the usual practice and
      the views of general and laboratory practitioners in the screening of prostate
      cancer using PSA. MATERIAL AND METHODS: A cross-sectional study based on a
      questionnaire and on PSA screening requests from Primary Health Care (PHC) in men
      older than 49 years with no prostatic symptoms. RESULTS: In 2015, PHC in
      Catalonia requested PSA on 15.2% of males. A total of 114 general practitioners
      and 227 laboratory practitioners participated in the questionnaire. The mean age
      of those who responded was 43 years with a mean of 17 years' experience, and
      included 64% women. According to general practitioners, 61% of PSA was performed
      at the patient's request. The uncertainty score when requesting PSA was 5 points
      for general practitioners and 5.7 for laboratory professionals. Interest in
      having clinical recommendations received 7.2 points in PHC, and 8.8 in the
      laboratory. Knowledge about the different clinical practice guidelines received
      was less than 5 points overall. CONCLUSIONS: General practitioners requested PSA
      screening in almost one-sixth of men over the age of 49 without prostate disease,
      often at the patient's request, and after informing them of the benefits and
      risks. PHC and laboratory physicians were interested in having recommendations
      and information, although they did not usually consult clinical practice
      guidelines immediately.

PMID- 29574009
TI  - [Epidemiology and management of community acquired pneumonia: more than 10 years
      experience].
AB  - OBJECTIVE: To describe the characteristics of patients diagnosed with Community
      Acquired Pneumonia in this basic health area, their management, outcomes, and use
      of prognostic scales driven by the few studies carried out from Primary Care on
      these aspects. MATERIAL AND METHODS: Descriptive cross-sectional study on a
      population diagnosed with Community Acquired Pneumonia if three urban health
      centres, during the period January 2000 to 31 July 2103. RESULTS: Out of a sample
      of 1,290 patients obtained, 56.1% were men, and the mean age of the population
      was 61.9 years. There were 22.7% smokers. More than half (59.9%) had a disease in
      the prognostic scales, with Diabetes Mellitus present in 20%, and 36.1% with
      pulmonary disease (17.6% COPD, 11.8% asthma). Just under half (43.2%) of the
      total patients were diagnosed in Primary Care. There was a diagnostic X-ray in
      92.7% of the cases, and a follow-up X-ray in 59.4%. Prognostic scales were
      recorded in 2% of the cases. The most commonly used antibiotics were amoxicillin
      clavulanic (30.7%) and levofloxacin (30.4%). Having prior disease increases the
      risk of re-treatment by 1.6 (95% CI; 1.1-2.2)]. The mortality risk is multiplied
      by 5.3 on having a previous disease (95% CI; 1.3-19.2). CONCLUSIONS: In the
      Primary Care setting, Community Acquired Pneumonia is a common and potentially
      serious disease which, in half the cases, occurs in patients with associated
      comorbidity. As regards treatment and management, is highlighted the wide use
      made of amoxicillin-clavulanic, compared to the low use of amoxicillin, combined
      therapy, and prognostic scales.

PMID- 29574010
TI  - Noradrenergic effects on olfactory perception and learning.
AB  - We here review modulation of olfactory guided behavioral tasks by noradrenaline.
      In this review we focus on modulation of the main olfactory system in adult
      rodents. We detail behavioral paradigms commonly used and discuss how sensory
      perception and learning can be measured using these paradigms. We then describe
      neuromodulatory effects on several aspects of olfactory processing, including
      detection and encoding. We describe how memory duration, specificity and duration
      are affected by noradrenergic modulation.

PMID- 29574011
TI  - Residue of insecticides in foodstuff and dietary exposure assessment of Brazilian
      citizens.
AB  - The goal of this work is to study the presence of 17 different pyrethroids and
      chlorpyrifos in animal origin food samples, including chicken, beef, fish, eggs
      and milk. The samples were analyzed by GC/NCI-MS/MS in order to determine their
      insecticide concentration levels, the relation between the amount of insecticides
      and the lipid content, as well as their isomeric composition. Bifenthrin,
      cypermethrin, cyhalothrin, permethrin, deltamethrin and chlorpyrifos have been
      detected in real samples. The highest levels find were verified for chlorpyrifos
      (45.7 MUg L-1, 17.5 MUg kg-1 ww) and cypermethrin (2.75 MUg L-1, 14.7 MUg kg-1
      ww) in milk and beef, respectively. The estimate of daily intake showed that none
      of these insecticides exceeded the safety limits of the acceptable daily intake
      values. A strong correlation between the amount of pesticides and lipid content
      was found for beef, fish and chicken samples. Regarding the isomers, a
      predominance of cis isomers in samples contaminated with cypermethrin was
      verified.

PMID- 29574012
TI  - Protection of cyanidin-3-O-glucoside against acrylamide- and glycidamide-induced
      reproductive toxicity in leydig cells.
AB  - Acrylamide (AA) occurs in many cooked carbohydrate-rich foods and has caused
      widespread concern as a possible carcinogen. Glycidamide (GA) is the ultimate
      genotoxic metabolite of AA. The present study was to investigate the protective
      effect of Cyanidin-3-O-glucoside (C3G) against AA- and GA-induced reproductive
      toxicity in R2C Leydig cells. The results demonstrated that C3G inhibited AA- and
      GA-induced cytotoxicity and mitochondria-mediated cell apoptosis, the effective
      doses of C3G were ranging from 10 to 50 MUM. Besides, AA (1.925 mM) and GA (0.872
      mM) exposure increased ROS level and decreased mitochondrial membrane potential,
      which led to a decrease in progesterone production, while C3G ranging from 10 to
      50 MUM reduced ROS immediately, and increased progesterone production after 24 h
      treatment. Furthermore, C3G up-regulated expression of Bcl-2 protein and down
      regulated pro-apoptotic protein Bax and cleaved Caspase-3 after 24 h treatment in
      1.925 mM AA- and 0.872 mM GA-treated R2C cells. Moreover, C3G intervention
      increased the protein expression of steroidogenic acute regulatory (StAR). It was
      concluded that C3G is effective in reducing AA- and GA-induced reproductive
      toxicity via inhibition of ROS generation, mitochondrial membrane depolarization
      and apoptosis, as well as activating steroidogenic enzymes.

PMID- 29574013
TI  - Functional constipation in children.

PMID- 29574015
TI  - Effects of platelet-rich plasma on tissue-engineered vascularized flaps in an in
      vivo chamber.
AB  - AIMS: We investigated the reproducibility of creating a vascularized tissue flap
      in an in vivo tissue engineering chamber by incubating a vascular pedicle
      imbedded in a collagen sponge with activated platelet-rich plasma (aPRP) and
      basic fibroblast growth factor (bFGF). METHODS: Collagen sponge soaked with
      saline (control group), bFGF (Group 1), aPRP (Group 2), and aPRP/controlled
      release bFGF (Group 3) was implanted with a saphenous arteriovenous pedicle into
      a tissue engineering chamber, located subcutaneously in the groin of rabbits.
      After 4 weeks of implantation, the contents in the chamber were harvested for
      volumetric and histological analyses. RESULTS: The total volume of generated
      tissue in Group 3 was the largest among the Groups (control group vs. Group 3, p
      < 0.01). The volume of the pedicle vascular bundle/adipose tissue component was
      larger in Groups 1 and 3 than that in the control group (p < 0.05 and p < 0.01,
      respectively). The inflammatory tissue volume was larger in Groups 2 and 3
      (control group vs. Group 3, p < 0.05). In a smaller long-term study, inflammatory
      tissue at 4 weeks was gradually replaced by the adipose tissue within 8 weeks.
      CONCLUSION: PRP-induced inflammatory reactions were considered to be necessary to
      stimulate cell migration into the chamber, leading to more tissue regeneration
      with abundant cell components. We conclude that PRP contributes to the
      reproducibility of preparing vascularized flaps in an in vivo chamber.

PMID- 29574016
TI  - International Journal of Antimicrobial Agents Themed Section Issue: "Therapeutics
      of hepatitis viruses".

PMID- 29574017
TI  - What Makes a Good Endoscopic Teacher: A Qualitative Analysis.
AB  - OBJECTIVE: Teaching learners to perform endoscopic procedures is challenging, yet
      effective endoscopy teaching practices are not well-described in the literature,
      and prior studies have focused on perspectives of supervising physicians rather
      than learners. We sought to characterize, from the perspective of endoscopy
      learners, endoscopic teaching behaviors perceived as beneficial and detrimental
      to learning using qualitative methods. DESIGN: This is a prospective qualitative
      content analysis. Gastroenterology fellows from 2 tertiary care centers
      anonymously provided feedback regarding supervising physicians' teaching
      behaviors during endoscopic training between March 2016 and December 2016.
      Preprinted cards were completed at the conclusion of procedures to document
      behaviors that fellows perceived as enhancing or hampering their learning. Two
      investigators performed content analysis of written comments; each identified
      behavior was assigned positive or negative valence. SETTING: Mount Sinai Hospital
      in New York, New York and University of California San Francisco in San
      Francisco, California. Both institutions are academic tertiary care centers.
      PARTICIPANTS: A total of 19 gastroenterology fellows at 2 training institutions
      participated. RESULTS: A total of 239 teaching behaviors were identified by 19
      fellows who worked with 31 supervising physicians; 29 unique behaviors were
      identified and organized into 7 themes: teaching, learning environment, autonomy,
      communication, coaching, feedback, and professionalism. Of all, 185 (77.4%)
      behaviors were reported as beneficial, and 54 (22.6%) as detrimental to the
      learning experience. Behaviors related to teaching were most often perceived as
      beneficial, while behaviors related to professionalism and communication were
      most often perceived as detrimental to learning. CONCLUSIONS: Specific teaching
      behaviors may help or hinder learning of endoscopic skills. These behaviors may
      be useful for efforts related to teaching evaluation, faculty development, and
      direct teaching.

PMID- 29574014
TI  - Notch signaling and neuronal death in stroke.
AB  - Ischemic stroke is a leading cause of morbidity and death, with the outcome
      largely determined by the amount of hypoxia-related neuronal death in the
      affected brain regions. Cerebral ischemia and hypoxia activate the Notch1
      signaling pathway and four prominent interacting pathways (NF-kappaB, p53, HIF
      1alpha and Pin1) that converge on a conserved DNA-associated nuclear multi
      protein complex, which controls the expression of genes that can determine the
      fate of neurons. When neurons experience a moderate level of ischemic insult, the
      nuclear multi-protein complex up-regulates adaptive stress response genes
      encoding proteins that promote neuronal survival, but when ischemia is more
      severe the nuclear multi-protein complex induces genes encoding proteins that
      trigger and execute a neuronal death program. We propose that the nuclear multi
      protein transcriptional complex is a molecular mediator of neuronal hormesis and
      a target for therapeutic intervention in stroke.

PMID- 29574018
TI  - Does Orthopaedic Training Compromise the Outcome in Knee Joint Arthroplasty?
AB  - OBJECTIVE: This study investigates knee joint arthroplasty and compares the
      outcomes between attending (consultant) orthopedic surgeons and resident
      (trainee) surgeons. DESIGN: Retrospective review and comparison of knee joint
      arthroplasty outcomes between 4 surgeon groups (attending, supervised senior and
      junior residents, and unsupervised senior residents). Measured outcomes were
      implant survival (revision rate) and patient reported functional outcomes,
      measured by Oxford knee score (OKS). SETTING: New Zealand arthroplasty service.
      PARTICIPANTS: Seventeen years of knee joint arthroplasty data from the New
      Zealand Joint Registry (NZJR) was reviewed. RESULTS: The New Zealand Joint
      Registry (NZJR) data showed 79,671 total knee arthroplasties (TKA) and 8854
      unicompartmental knee arthroplasties (UKA) performed between 1999 and 2016.
      Attending surgeons performed 90% and 97% of TKA and UKA, respectively. The number
      and proportion of resident performed knee joint arthroplasty has decreased.
      Faster operation times was observed in the attending surgeon group. Attending
      surgeon revision rate was 0.49 and 1.19/100 component years for TKA and UKA,
      respectively, this was not significantly increased in resident surgeon groups.
      Postoperative OKS was 37.7 and 39.7 for attending surgeon performed TKA and UKA,
      respectively. Mean OKS were less than 2 points worse in resident groups (resident
      range: 36.3-36.9) compared to attending colleagues for TKA, but for UKA scores
      were up to 11 points worse (resident range: 28.9-38.8). CONCLUSIONS: New Zealand
      has a high rate of attending surgeon performed TKA and UKA. Revision rates were
      not increased in resident surgeon groups. Postoperative function was not reduced
      by a clinically significant amount in TKA in any of the resident surgeon groups
      but was reduced in supervised junior resident and unsupervised senior resident
      surgeon groups for UKA.

PMID- 29574019
TI  - Investigating the Effect of Simulator Functional Fidelity and Personalized
      Feedback on Central Venous Catheterization Training.
AB  - OBJECTIVE: To compare the effect of simulator functional fidelity (manikin vs a
      Dynamic Haptic Robotic Trainer [DHRT]) and personalized feedback on surgical
      resident self-efficacy and self-ratings of performance during ultrasound-guided
      internal jugular central venous catheterization (IJ CVC) training. In addition,
      we seek to explore how self-ratings of performance compare to objective
      performance scores generated by the DHRT system. DESIGN: Participants were
      randomly assigned to either manikin or DHRT IJ CVC training over a 6-month
      period. Self-efficacy surveys were distributed before and following training.
      Training consisted of a pretest, 22 practice IJ CVC needle insertion attempts, 2
      full-line practice attempts, and a posttest. Participants provided self-ratings
      of performance for each needle insertion and were presented with feedback from
      either an upper level resident (manikin) or a personalized learning system
      (DHRT). SETTING: A study was conducted from July 2016 to February 2017 through a
      surgical skills training program at Hershey Medical Center in Hershey,
      Pennsylvania. PARTICIPANTS: Twenty-six first-year surgical residents were
      recruited for the study. Individuals were informed that IJ CVC training
      procedures would be consistent regardless of participation in the study and that
      participation was optional. All recruited residents opted to participate in the
      study. RESULTS: Residents in both groups significantly improved their self
      efficacy scores from pretest to posttest (p < 0.01). Residents in the manikin
      group consistently provided higher self-ratings of performance (p < 0.001).
      Residents in the DHRT group recorded more feedback on errors (228 instances) than
      the manikin group (144 instances). Self-ratings of performance on the DHRT system
      were able to significantly predict the objective score of the DHRT system (R2 =
      0.223, p < 0.001). CONCLUSION: Simulation training with the DHRT system and the
      personalized learning feedback can improve resident self-efficacy with IJ CVC
      procedures and provide sufficient feedback to allow residents to accurately
      assess their own performance.

PMID- 29574020
TI  - SIRT1 and microRNAs: The role in breast, lung and prostate cancers.
AB  - Breast cancer and prostate cancer are the most common malignant tumors in female
      and men, respectively. Furthermore, lung cancer is the leading cause of cancer
      deaths worldwide. It is an emergency to develop a powerful strategy to treat
      these threatening cancers more effectively, because of low efficacy and high
      rates of chemotherapy effects. MicroRNAs (miRNAs), a class of small non-coding
      RNAs, are key regulators of gene expression via induction of translational
      repression or mRNA degradation. MiRNA deregulation has been linked to cancer
      initiation and progression. Silent Inflammation Regulator 2 (SIR2) proteins
      sirtuins- are a family of histone deacetylases (HDACs) that catalyze
      deacetylation of both histone and non- histone lysine residues. SIRT1 can act as
      an oncogene. It plays a role in tumorigenesis by anti-apoptotic activity and is
      implicated in diverse cellular process including autophagy, senescence,
      apoptosis, proliferation, and aging. MicroRNAs and SIRT1 serve as tumor
      suppressors or tumor promotors depending on the oncogenic pathway specific to
      particular tumors. MicroRNAs modulate cancer development by targeting SIRT1. In
      this review, we underlie the specific mechanisms involved in these threatening
      cancers by microRNAs/SIRT1 pathways.

PMID- 29574021
TI  - HIF-dependent and reversible nucleosome disassembly in hypoxia-inducible gene
      promoters.
AB  - Hypoxia causes dramatic changes in gene expression profiles, and the mechanism of
      hypoxia-inducible transcription has been analyzed for use as a model system of
      stress-inducible gene regulation. In this study, changes in chromatin
      organization in promoters of hypoxia-inducible genes were investigated during
      hypoxia-reoxygenation conditions. Most of the hypoxia-inducible gene promoters
      were hypersensitive to DNase I under both normal and hypoxic conditions, and our
      data indicate an immediate recruitment of transcription factors under hypoxic
      conditions. In some of the hypoxia-inducible promoters, nucleosome-free DNA
      regions (NFRs) were established in parallel with hypoxia-induced transcription.
      We also show that the hypoxia-inducible formation of NFRs requires that hypoxia
      inducible transcription factors (HIFs) bind to the promoters together with the
      transcriptional coactivator CBP. Within 1 h after the hypoxia exposure was ended
      (reoxygenation), HIF complexes were dissociated from the promoter regions. Within
      24 h of reoxygenation, the hypoxia-induced transcription returned to basal levels
      and the nucleosome structure was reassembled in the hypoxia-inducible NFRs.
      Nucleosome reassembly required the function of the transcriptional coregulator
      SIN3A. Thus, reversible changes in nucleosome organization mediated by
      transcription factors are notable features of stress-inducible gene regulation.

PMID- 29574022
TI  - Analysis of TCRbeta and TCRgamma genes in Chinese alligator provides insights
      into the evolution of TCR genes in jawed vertebrates.
AB  - All jawed vertebrates have four T cell receptor (TCR) chains that are expressed
      by thymus-derived lymphocytes and play a major role in animal immune defence.
      However, few studies have investigated the TCR chains of crocodilians compared
      with those of birds and mammals, despite their key evolutionary position linking
      amphibians, reptiles, birds and mammals. Here, employing an Alligator sinensis
      genomic bacterial artificial chromosome (BAC) library and available genome data,
      we characterized the genomic organization, evolution and expression of TRB and
      TRG loci in Alligator sinensis. According to the sequencing data, the Alligator
      sinensis TRB locus spans approximately 500 Kb of genomic DNA containing two D-J-C
      clusters and 43 V gene segments and is organized as Vbeta(39)-pJbeta1-pCbeta1
      pDbeta1-Dbeta2- Jbeta2(12)-Cbeta2-Vbeta(4), whereas the TRG locus spans 115 Kb of
      DNA genomic sequence consisting of 18 V gene segments, nine J gene segments and
      one C gene segment and is organized in a classical translocon pattern as
      Vgamma(18)-Jgamma(9)-Cgamma. Moreover, syntenic analysis of TRB and TRG chain
      loci suggested a high degree of conserved synteny in the genomic regions across
      mammals, birds and Alligator sinensis. By analysing the cloned TRB/TRG cDNA, we
      identified the usage pattern of V families in the expressed TRB and TRG. An
      analysis of the junctions of the recombined VJ revealed the presence of N and P
      nucleotides in both expressed TRB and TRG sequences. Phylogenetic analysis
      revealed that TRB and TRG loci possess distinct evolutionary patterns. Most
      Alligator sinensis V subgroups have closely related orthologues in chicken and
      duck, and a small number of Alligator sinensis V subgroups have orthologues in
      mammals, which supports the hypothesis that crocodiles are the closest relatives
      of birds and mammals. Collectively, these data provide insights into TCR gene
      evolution in vertebrates and improve our understanding of the Alligator sinensis
      immune system.

PMID- 29574023
TI  - Progression of Treated versus Untreated Liver Imaging Reporting and Data System
      Category 4 Masses after Transcatheter Arterial Embolization Therapy.
AB  - PURPOSE: To compare outcomes of treated vs untreated Liver Imaging Reporting and
      Data System category 4 (LR-4) masses after transcatheter arterial embolization.
      MATERIALS AND METHODS: In 167 patients undergoing embolization for HCC from
      January 2005 to December 2012, LR-4 masses were retrospectively identified on CT
      and MR imaging examinations performed before embolization. In 149 patients
      undergoing embolization from January 2013 to December 2016, masses prospectively
      classified as LR-4 were identified. In total, there were 81 LR-4 masses in 62
      patients (16 women; mean age 62 y; range 29-83 y). Procedures were reviewed to
      determine whether LR-4 masses were within or outside the liver volume that
      received embolization during treatment of dominant masses. Time to progression to
      LR-5 and by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was
      estimated for treated vs untreated LR-4 masses using the Kaplan-Meier method and
      compared using the log rank test. RESULTS: LR-4 masses averaged 1.8 cm; 88%, 60%,
      14%, and 14% demonstrated arterial phase hyperenhancement, washout, a capsule,
      and growth. Of LR-4 masses, 62 were within the liver volume that received
      embolization and considered treated, and 19 were outside and considered
      untreated. Response rates according to mRECIST were 37% vs 21% for treated vs
      untreated masses (P = .27). The 6- and 12-month rates of progression to LR-5 were
      7% and 26% for treated masses vs 27% and 75% for untreated masses (P = .001).
      According to mRECIST, 7% and 27% of treated masses progressed vs 30% and 65% of
      untreated masses (P = .001). CONCLUSIONS: LR-4 masses that receive embolization
      in the setting of dominant masses elsewhere show lower rates of progression
      compared with untreated masses.

PMID- 29574025
TI  - Effects of Multi-Electrode Renal Denervation on Insulin Sensitivity and Glucose
      Metabolism in a Canine Model of Type 2 Diabetes Mellitus.
AB  - PURPOSE: To evaluate the effects of multi-electrode catheter-based renal
      denervation (RDN) on insulin sensitivity and glucose metabolism in a type 2
      diabetes mellitus (T2DM) canine model. MATERIALS AND METHODS: Thirty-three dogs
      were divided equally into 3 groups: bilateral renal denervation (BRDN) group,
      left renal denervation (LRDN) group, and sham operation (SHAM) group. Body weight
      and blood biochemistry were measured at baseline, 20 weeks, and 32 weeks, and
      renal angiography and computerized tomographic (CT) angiography were determined
      before the procedure and 1 month, 2 months, and 3 months after the procedure.
      Western blot was used to identify the activities of gluconeogenic enzymes and
      insulin-signaling proteins. RESULTS: Fasting plasma glucose (9.64 +/- 1.57 mmol/L
      vs 5.12 +/- 1.08 mmol/L; P < .0001), fasting insulin (16.19 +/- 1.43 mIU/mL vs
      5.07 +/- 1.13 mIU/mL; P < .0001), and homeostasis-model assessment of insulin
      resistance (HOMA-IR; 6.95 +/- 1.33 vs 1.15 +/- 0.33; P < .0001) in the BRDN group
      had significantly decreased at the 3-month follow-up compared with the SHAM
      group. Western blot analyses showed that RDN suppressed the gluconeogenetic
      genes, modulated insulin action, and activated insulin receptors-AKT signaling
      cascade in the liver. CT angiography and histopathologic analyses did not show
      any dissection, aneurysm, thrombus, or rupture in any of the renal arteries.
      CONCLUSIONS: These findings identified that multi-electrode catheter-based RDN
      could effectively decrease gluconeogenesis and glycogenolysis, resulting in
      improvements in insulin sensitivity and glucose metabolism in a T2DM canine
      model.

PMID- 29574024
TI  - Quality Improvement Guidelines for Mesenteric Angioplasty and Stent Placement for
      the Treatment of Chronic Mesenteric Ischemia.

PMID- 29574026
TI  - In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and
      1,3,4-thiadiazole.
AB  - The initial steps in preclinical drug developing research concern the synthesis
      of new compounds for specific therapeutic use which needs to be confirmed by in
      vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically
      labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4
      thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2
      adamantylthiazol[3,2-b][1,2,4]triazol-6(5H)ones (5-8); and an ethylaminothiazole
      based chalcone (9), were tested for antioxidant activity (AOA) by using three in
      vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP
      (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive
      substances test). Compounds 1-4 and 9 in particular are newly synthesized
      compounds. Also, traditional antioxidants Vitamins E and C and alpha-lipoic acid
      (alpha-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E
      2.99% and alpha-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3
      4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO
      inhibition): Vitamin C 62.32%; Vitamin E 36.29%; alpha-LA 51.36%; compounds: 1
      62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated ~50%; 3 and 8 displayed ~38%;
      2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, ~100%, unlike alpha
      LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA
      of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox
      reaction principles between these assays dictate different AOA outcomes for a
      single compound. Vitamin C appeared to be the superior antioxidant out of the
      traditional antioxidants; and compound 4 was superior to other tested
      thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out
      of the traditional antioxidants; and compound 4 was superior to other tested
      thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbonyl
      functional domains and chelating ligand properties of the thiazolidinone
      derivatives correlated with AOA.

PMID- 29574028
TI  - An Alarming but Benign Appearance, A Case of Pseudomelanosis Duodeni.

PMID- 29574027
TI  - Lymphoepithelioma-Like Gastric Carcinoma Misdiagnosed as a Submucosal Tumor.

PMID- 29574029
TI  - Jejunogastric Intussusception With Jejunojejunal Intussusception (Double
      Telescoping).

PMID- 29574030
TI  - An Unusual Aspirate and Microbiopsy of a Pancreas Cyst Diagnostic for Pancreatic
      Lymphangioma.

PMID- 29574031
TI  - Gastric Metastasis of Hepatocellular Carcinoma Mimicking Early Gastric Cancer.

PMID- 29574032
TI  - Nonhealing Gastric Ulcer Due to Mesh Eroding Through Gastric Wall.

PMID- 29574035
TI  - Effects of short term lead exposure on gut microbiota and hepatic metabolism in
      adult zebrafish.
AB  - Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that has
      been associated with a wide range of toxic effects in humans and environmental
      animals. Here, effects of short time exposure to 10 and 30 MUg/L Pb on gut
      microbiota and hepatic metabolism were analyzed in adult male zebrafish. We
      observed that both 10 and 30 MUg/L Pb increased the volume of mucus in the gut.
      At phylum level, the abundance of alpha-Proteobacteria decreased significantly
      and the abundance of Firmicutes increased significantly in the gut when treated
      with 30 MUg/L Pb for 7 days. In addition, the 16S rRNA gene sequencing for V3-V4
      region revealed a significant change in the richness and diversity of gut
      microbiota in 30 MUg/L Pb exposed group. A more depth analysis, at the genus
      level, discovered that 52 gut microbes identified by operational taxonomic unit
      analysis were changed significantly in 30 MUg/L Pb treated group. Based on GC/MS
      metabolomics analysis, a total of 41 metabolites were significantly altered in 30
      MUg/L Pb treatment group. These changed metabolites were mainly associated with
      the pathways of glucose and lipid metabolism, amino acid metabolism, nucleotide
      metabolism. In addition, we also confirmed that the transcription of some genes
      related to glycolysis and lipid metabolism, including Gk, Aco, Acc1, Fas, Apo and
      Dgat, decreased significantly in the liver of zebrafish when exposed to 30 MUg/L
      Pb for 7 days. Our results observed that Pb could cause gut microbiota dysbiosis
      and hepatic metabolic disorder in zebrafish.

PMID- 29574033
TI  - Computational neuroanatomy of baby brains: A review.
AB  - The first postnatal years are an exceptionally dynamic and critical period of
      structural, functional and connectivity development of the human brain. The
      increasing availability of non-invasive infant brain MR images provides
      unprecedented opportunities for accurate and reliable charting of dynamic early
      brain developmental trajectories in understanding normative and aberrant growth.
      However, infant brain MR images typically exhibit reduced tissue contrast
      (especially around 6 months of age), large within-tissue intensity variations,
      and regionally-heterogeneous, dynamic changes, in comparison with adult brain MR
      images. Consequently, the existing computational tools developed typically for
      adult brains are not suitable for infant brain MR image processing. To address
      these challenges, many infant-tailored computational methods have been proposed
      for computational neuroanatomy of infant brains. In this review paper, we provide
      a comprehensive review of the state-of-the-art computational methods for infant
      brain MRI processing and analysis, which have advanced our understanding of early
      postnatal brain development. We also summarize publically available infant
      dedicated resources, including MRI datasets, computational tools, grand
      challenges, and brain atlases. Finally, we discuss the limitations in current
      research and suggest potential future research directions.

PMID- 29574034
TI  - Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review.
AB  - Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular reserve and
      provides important information about vascular health in a range of brain
      conditions and diseases. Unlike steady-state vascular parameters, such as
      cerebral blood flow (CBF) and cerebral blood volume (CBV), CVR measures the
      ability of cerebral vessels to dilate or constrict in response to challenges or
      maneuvers. Therefore, CVR mapping requires a physiological challenge while
      monitoring the corresponding hemodynamic changes in the brain. The present review
      primarily focuses on methods that use CO2 inhalation as a physiological challenge
      while monitoring changes in hemodynamic MRI signals. CO2 inhalation has been
      increasingly used in CVR mapping in recent literature due to its potency in
      causing vasodilation, rapid onset and cessation of the effect, as well as
      advances in MRI-compatible gas delivery apparatus. In this review, we first
      discuss the physiological basis of CVR mapping using CO2 inhalation. We then
      review the methodological aspects of CVR mapping, including gas delivery
      apparatus, the timing paradigm of the breathing challenge, the MRI imaging
      sequence, and data analysis. In addition, we review alternative approaches for
      CVR mapping that do not require CO2 inhalation.

PMID- 29574036
TI  - Prognostic Scoring System for Patients Undergoing Reconstructive Foot and Ankle
      Surgery for Charcot Neuroarthropathy: The Charcot Reconstruction Preoperative
      Prognostic Score.
AB  - Charcot neuroarthropathy is a destructive process that occurs in patients with
      peripheral neuropathy, often due to poorly controlled diabetes mellitus. Surgical
      reconstruction can be necessary to provide a plantigrade foot that is wound free.
      A risk of major amputation exists after a Charcot event and after attempted
      reconstruction. We retrospectively reviewed the data from 34 patients (36
      reconstructions) who had undergone reconstructive surgery for Charcot
      neuroarthropathy. The mean patient age was 56.44 years. The mean follow-up period
      was 56 months. We collected patient age, body mass index, presence of wound or
      osteomyelitis, anatomic location, activity of disease, and hemoglobin A1c. Using
      these data, each patient was given a score using our novel prognostic scoring
      system, the Charcot Reconstruction Preoperative Prognostic Score (CRPPS). Our
      primary outcome measure was no wound and no major amputation at the final follow
      up visit. The limb salvage rate was 89% (32 of 36), and 78% (28 of 36) had no
      wound at the final follow-up examination. For patients without a wound or major
      amputation at the final follow-up visit, the mean CRPPS was 2.96 +/- 1.23. The
      mean CRPPS for those with a wound or major amputation at the final follow-up
      visit was 4.33 +/- 1.07 (p = .0024). Univariate logistic regression revealed 2
      statistically significant predictors of wound and/or amputation: anatomic
      location (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.051 to 23.789; p =
      .043) and CRPPS (OR 2.724, 95% CI 1.274 to 5.823, p = .01). A CRPPS of >=4 was
      also predictive of a negative outcome (OR 7.286, 95% CI 1.508 to 35.211; p =
      .013). This scoring system, with a sensitivity of 75%, specificity of 71%, and
      negative predictive value of 85%, is a potential starting point when educating
      patients and making treatment decisions in this exceptionally challenging group.

PMID- 29574037
TI  - Microsurgical Replantation of the Posterior Heel Skin and Subcutaneous Tissue.
AB  - A 45-year-old male presented with amputation of posterior heel soft tissue after
      an accident involving broken glass panes. The defect measured 4 * 6.5 cm, and the
      composite amputated tissue consisted of skin and subcutaneous layers.
      Intraoperative exploration of the amputated tissue revealed 2 perforator arteries
      (diameter <=0.4 mm) in the central portion of the subcutaneous tissue and 4
      superficial veins (diameter ~0.6 mm) in the wound margin. These vessels were
      anastomosed end-to-end to the corresponding vessels from the wound bed using 11-0
      nylon sutures. The replanted tissue survived completely. The patient retained
      excellent aesthetic and functional outcomes at the 13-month follow-up visit. The
      present case serves to demonstrate the feasibility of microsurgical replantation
      for the posterior heel. Although such isolated amputations are far less common
      than digital amputations, our experience suggests that microsurgical replantation
      is indicated beyond the current spectrum of clinical repertoire.

PMID- 29574038
TI  - Reply.

PMID- 29574040
TI  - Epigenetics as biomarkers in autoimmune diseases.
AB  - Autoimmune diseases are immune system disorders in which immune cells cannot
      distinguish self-antigens from foreign ones. The current criteria for autoimmune
      disease diagnosis are based on clinical manifestations and laboratory tests.
      However, none of these markers shows both high sensitivity and specificity. In
      addition, some autoimmune diseases, for example, systemic lupus erythematosus
      (SLE), are highly heterogeneous and often exhibit various manifestations. On the
      other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE,
      share similar symptoms and autoantibodies, which also causes difficulties in
      diagnosis. Therefore, biomarkers that have both high sensitivity and high
      specificity for diagnosis, reflect disease activity and predict drug response are
      necessary. An increasing number of publications have proposed the abnormal
      epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this
      review will comprehensively summarize the epigenetic progress in the pathogenesis
      of autoimmune disorders and unearth potential biomarkers that might be
      appropriate for disease diagnosis and prediction.

PMID- 29574039
TI  - Phase Ib trial of folate binding protein (FBP)-derived peptide vaccines, E39 and
      an attenuated version, E39': An analysis of safety and immune response.
AB  - : In this randomized phase Ib trial, we tested combining the E39 peptide vaccine
      with a vaccine created from E39', an attenuated version of E39. Patients with
      breast or ovarian cancer, who were disease-free after standard of care therapy,
      were enrolled and randomized to one of three arms. Arm EE received six E39
      inoculations; arm EE' received three E39 inoculations followed by three E39'; and
      arm E'E received three E39' inoculations, followed by three E39. Within each arm,
      the first five patients received 500 MUg of peptide and the remainder received
      1000 MUg. Patients were followed for toxicity, and immune responses were
      measured. This initial analysis after completion of the primary vaccination
      series has confirmed the safety of both vaccines. Immune analyses suggest
      incorporating the attenuated version of the peptide improves immune responses and
      that sequencing of E39 followed by E39' might produce the optimal immune
      response. TRIAL REGISTRATION: NCT02019524.

PMID- 29574041
TI  - In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for
      exenatide.
AB  - BACKGROUND: The aim of the study was to develop an oral self-emulsifying drug
      delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy.
      METHODS: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate
      (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil
      1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized
      in terms of lipophilicity evaluating the octanol/water phase distribution (logP).
      Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release
      characteristics (log DSEDDS/release medium determination) and mucus permeation
      studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on
      blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats.
      RESULTS: Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC)
      increased the effective logP of exenatide from -1.1 to 2.1. SEDDS with a payload
      of 1% exenatide/DOC had a mean droplet size of 45.87 +/- 2.9 nm and a Log
      DSEDDS/release medium of 1.9 +/- 0.05. Permeation experiments revealed 2.7-fold
      improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in
      solution. Orally administered exenatide/DOC SEDDS showed a relative
      bioavailability (versus s.c.) of 14.62% +/- 3.07% and caused a significant (p <
      .05) 20.6% decrease in AUC values of blood glucose levels. CONCLUSION: According
      to these results, hydrophobic ion pairing in combination with SEDDS represents a
      promising tool for oral peptide delivery.

PMID- 29574042
TI  - Modeling the performance of carrier-based dry powder inhalation formulations:
      Where are we, and how to get there?
AB  - Development of carrier-based dry powder inhalation formulations follows till date
      empirical approaches. This is mainly underlain by numerousness of interplaying
      determinants of performance and complexity of involved interactions. Mathematical
      modeling helps elucidate such interactions and aids rational development of
      formulations. This article provides a critical overview of attempts made to model
      the performance of carrier-based dry powder inhalation formulations. The complex
      dependence of the performance on formulation properties is comprehensively
      discussed. A potential microstructure-based model is ultimately introduced.

PMID- 29574043
TI  - Eating patterns of US adults: Meals, snacks, and time of eating.
AB  - The objective of this paper is to update knowledge of eating patterns of US
      adults with sex and ethnicity specific estimates and discuss the implications of
      reported patterns with respect to current resurgence of interest in the topic.
      The eating patterns data were from the NHANES 2009-2014 (n = 15,341 adults).
      Overall, American adults reported 4.96 +/- 0.03 eating episodes in the recall.
      Women were more likely to report each of the three main meals and all three meals
      plus one or more snacks relative to men (P < 0.0001). Relative to other ethnic
      groups, non-Hispanic blacks were less likely to report each meal or a snack or
      all three meals, and the foods reported for meals and snacks were higher in
      energy density (P = 0.0001). Of the three meals, the dinner meal, and among
      snacks, the after-dinner snack, were reported by the highest percentage of
      Americans; these two eating episodes provided nearly 45% of the 24-h energy
      intake. The average dinnertime was 6:24 pm, and the average time of the last
      eating episode of the 24-h ingestive period was 8:18 pm. Given these findings,
      adoption of eating patterns that advocate less frequent eating and shift in the
      time of eating are likely to present a challenge. We know little about the
      validity of eating patterns determined from 24-h recalls or questionnaire
      instruments. The extent of within person variability and reporting errors in
      different eating pattern components also need further research.

PMID- 29574044
TI  - Ultrasonic vocalization in juvenile and adult male rats: A comparison among
      stocks.
AB  - Ultrasonic vocalizations (USV) are widely studied in mice and rats, and in case
      of rats, the bulk of empirical evidence is based on outbred rats, which in most
      studies belong to either Long Evans, Sprague-Dawley or Wistar stocks. It is known
      that these stocks can differ in terms of specific brain variables and also
      behaviorally, but there is only few evidence so far showing whether these stocks
      behave in similar or substantially different ways in paradigms which are often
      used to study USV. Therefore, we have started a larger series of comparative
      studies, where we analyzed different classes of USV in rats from these three
      stocks spanning from pups to adults. Here, we report our findings in juvenile and
      adult male Long Evans, Sprague-Dawley and Wistar rats, which we tested as
      juveniles for appetitive 50-kHz calls during a so-called cage test or when being
      tickled by an experimenter, and later as adults for 22-kHz calls in a fear
      conditioning paradigm. In general, all three stocks showed the expected USV
      responses, indicating that they are all feasible for this kind of research. In
      detail, however, there were various quantitative differences between stocks both,
      in terms of specific USV features (like call rates, call durations etc.) as well
      as visible behavior, like spontaneous locomotor activity and shock-induced
      immobility. These findings are discussed in the context of the relevant, but
      somewhat equivocal literature on these stocks, including factors which might
      contribute to such variability, like breeding, housing, or details of the given
      test.

PMID- 29574045
TI  - SOX2 expression diminishes with ageing in several tissues in mice and humans.
AB  - SOX2 (Sex-determining region Y box 2) is a transcription factor expressed in
      several foetal and adult tissues and its deregulated activity has been linked to
      chronic diseases associated with ageing. Nevertheless, the level of SOX2
      expression in aged individuals at the tissue level has not previously been
      examined. In this work, we show that SOX2 expression decreases significantly in
      the brain with ageing, in both humans and rodents. The administration of
      resveratrol for 6 months in mice partly attenuated this reduction. We also
      identified an age-related decline in SOX2 mRNA and protein expression in several
      other organs, namely, the lung, heart, kidney, spleen and liver. Moreover,
      peripheral blood mononuclear cells (PBMCs) from elderly expressed lower levels of
      SOX2 than those from young individuals. Mechanistically, SOX2 expression
      inversely correlates with p16Ink4a levels. Together, these data show a widespread
      decrease in SOX2 with age, suggesting that the decline in SOX2 expression might
      be used as a biomarker of ageing.

PMID- 29574046
TI  - Editorial commentary: Preserving myocardium in muscular dystrophy patients using
      ACE inhibition.

PMID- 29574047
TI  - Psychoanalysis in modern mental health practice.
AB  - Like any discipline, psychoanalysis has evolved considerably since its inception
      by Freud over a century ago, and a multitude of different psychoanalytic
      traditions and schools of theory and practice now exist. However, some of Freud's
      original ideas, such as the dynamic unconscious, a developmental approach,
      defence mechanisms, and transference and countertransference remain essential
      tenets of psychoanalytic thinking to this day. This Review outlines several areas
      within modern mental health practice in which contemporary adaptations and
      applications of these psychoanalytic concepts might offer helpful insights and
      improvements in patient care and management, and concludes with an overview of
      evidence-based psychoanalytically informed treatments and the links between
      psychoanalysis, attachment research, and neuroscience.

PMID- 29574048
TI  - Facing fentanyl: should the USA consider trialling prescription heroin?

PMID- 29574049
TI  - Pain Sensitivity and Thermal Detection Thresholds in Young Adults Born Preterm
      With Very Low Birth Weight or Small for Gestational Age at Term Compared With
      Controls.
AB  - : The objective of this prospective long-term follow-up study was to investigate
      whether somatosensory function is altered among young adults born preterm with
      very low birth weight (VLBW; <=1,500 g) or small for gestational age (SGA; <10th
      percentile) at term. In a blinded quantitative sensory testing protocol, we
      determined thermal detection, thermal pain, and pressure pain thresholds and the
      response to prolonged supra-threshold heat among 51 VLBW, 66 term SGA, and 86
      term-born controls (birth weight >=10th percentile) at 28 years. Self-reported
      chronic pain was also investigated. Except for increased sensitivity to cool in
      the term SGA group versus controls, we found no significant group differences
      regarding thermal or pain thresholds. Overall, male participants had higher pain
      thresholds, and no significant interactions of group and sex were observed (P >
      .14). Within the VLBW group, neonatal mechanical ventilation was associated with
      reduced sensitivity to cool, and length of mechanical ventilation correlated with
      lower pressure pain thresholds. The response to prolonged supra-threshold heat
      was similar between the groups, and the prevalence of self-reported chronic pain
      was not reliably different. In conclusion, low birth weight young adults were as
      sensitive to thermal and pain stimuli as term-born, normal birth weight controls,
      with the same sex differences. PERSPECTIVE: To our knowledge, this is the first
      report on thermal and pain sensitivity among young adults born preterm with VLBW
      or SGA at term. The negative results from a comprehensive quantitative sensory
      testing protocol oppose previous findings of altered sensory perception among
      children and adolescents born preterm.

PMID- 29574050
TI  - Inference from the stationary distribution of allele frequencies in a family of
      Wright-Fisher models with two levels of genetic variability.
AB  - The distribution of allele frequencies obtained from diffusion approximations to
      Wright-Fisher models is useful in developing intuition about the population level
      effects of evolutionary processes. The statistical properties of the stationary
      distributions of K-allele models have been extensively studied under neutrality
      or under selection. Here, we introduce a new family of Wright-Fisher models in
      which there are two hierarchical levels of genetic variability. The genotypes
      composed of alleles differing from each other at the selected level have fitness
      differences with respect to each other and evolve under selection. The genotypes
      composed of alleles differing from each other only at the neutral level have the
      same fitness and evolve under neutrality. We show that with an appropriate
      scaling of the mutation parameter with respect to the number of alleles at each
      level, the frequencies of alleles at the selected and the neutral level are
      conditionally independent of each other, conditional on knowing the number of
      alleles at all levels. This conditional independence allows us to simulate from
      the joint stationary distribution of the allele frequencies. We use these
      simulated frequencies to perform inference on parameters of the model with two
      levels of genetic variability using Approximate Bayesian Computation.

PMID- 29574051
TI  - Dimethylsulfoniopropionate biosynthesis in a diatom Thalassiosira pseudonana:
      Identification of a gene encoding MTHB-methyltransferase.
AB  - Dimethylsulfoniopropionate (DMSP) is one of the most abundant molecules on earth
      and plays a pivotal role in the marine sulfur cycle. DMSP is believed to be
      synthesized from methionine by a four-step reaction pathway in marine algae. The
      genes responsible for biosynthesis of DMSP remain unidentified. A diatom
      Thalassiosira pseudonana CCMP1335 is an important component of marine ecosystems
      and contributes greatly to the world's primary production. In this study, through
      genome search, in vivo activity and functional studies of cDNA products, a gene
      encoding Thalassiosira methyltransferase (TpMMT) which catalyzes the key step of
      DMSP synthesis formation of 4-methylthio-2-hydroxybutyrate (DMSHB) from 4
      methylthio-2-oxobutyrate (MTHB), was identified. The amino acid sequence of TpMMT
      was homologous to the methyltransferase from Phaeodactylum tricornutum CCAP
      1055/1, but not the recently identified bacterium gene. High salinity and
      nitrogen limitation stresses caused the increase of DMSP content and TpMMT
      protein in Thalassiosira. In addition to TpMMT, the enzyme activities for the
      first three steps could be detected and enhanced under high salinity, suggesting
      the importance of four-step DMSP synthetic pathway in Thalassiosira.

PMID- 29574052
TI  - Lymphatic metabolites of quercetin after intestinal administration of quercetin-3
      glucoside and its aglycone in rats.
AB  - Quercetin is a major flavonoid, present as its glycosidic forms in plant foods.
      In this study, quercetin-3-glucoside (Q3G) was administered intraduodenally to
      thoracic lymph-cannulated rats, and its lymphatic transport was investigated. The
      resulting lymphatic and plasma metabolites were identified with LC-MS/MS and
      compared with those after administration of quercetin aglycone. The total
      concentration of quercetin metabolites in the lymph was about four times lower
      than that in the plasma, and quercetin and its methylated form isorhamnetin were
      detected as their glucuronides, sulfates and diglucuronides both in the lymph and
      the plasma after Q3G and quercetin administrations. The lymph levels of the
      glucuronides after Q3G administration were lower than those after quercetin
      administration, whereas those in the plasma showed the opposite pattern. Both the
      lymph and plasma levels of the sulfates after Q3G administration were lower than
      those after quercetin administration. Some of the intestinal metabolites like
      quercetin monoglucuronides were transported directly into the lymph and the
      hepatic metabolites like the diglucuronides were eventually transferred from the
      plasma into the lymph. These results indicate that the absorbed Q3G is partly
      transported into the intestinal lymph as quercetin metabolites. Deglycosylation
      in the enterocyte is also suggested to affect the subsequent metabolic pathways.

PMID- 29574053
TI  - About a case of traumatic separation of the cervix from the uterine corpus,
      diagnosed in a context of infertility.
AB  - This article reports a case of cervico-isthmic disjunction unnoticed during
      childhood, diagnosed in a context of primary infertility and endometriosis, and
      surgically treated. It is an uncommon condition. The diagnosis is most often made
      as part of an assessment of primary amenorrhea in a young woman with a history of
      severe pelvic trauma. It is suspected after imaging assessment and confirmed
      intraoperatively. The treatment consists in an anastomosis between the cervix and
      the uterine body, after individualizing these two structures, around a drain
      guiding healing. After this surgery, multiple pregnancies have been successfully
      carried out.

PMID- 29574054
TI  - Uterine transplantation: Review in human research.
AB  - Uterine transplantation is the solution to treat absolute uterine fertility. In
      this review, we present the historical, medical, technical, psychological and
      ethical perspectives in human uterine transplantation research. We reviewed the
      PubMed database following PRISMA guidelines and added data presented by several
      research teams during the first international congress on uterine
      transplantation.

PMID- 29574055
TI  - Tuning Transcriptional Regulation through Signaling: A Predictive Theory of
      Allosteric Induction.
AB  - Allosteric regulation is found across all domains of life, yet we still lack
      simple, predictive theories that directly link the experimentally tunable
      parameters of a system to its input-output response. To that end, we present a
      general theory of allosteric transcriptional regulation using the Monod-Wyman
      Changeux model. We rigorously test this model using the ubiquitous simple
      repression motif in bacteria by first predicting the behavior of strains that
      span a large range of repressor copy numbers and DNA binding strengths and then
      constructing and measuring their response. Our model not only accurately captures
      the induction profiles of these strains, but also enables us to derive analytic
      expressions for key properties such as the dynamic range and [EC50]. Finally, we
      derive an expression for the free energy of allosteric repressors that enables us
      to collapse our experimental data onto a single master curve that captures the
      diverse phenomenology of the induction profiles.

PMID- 29574057
TI  - A nomogram for classification of temporomandibular joint disk perforation based
      on magnetic resonance imaging.
AB  - OBJECTIVE: The aim of this study was to analyze risk factors and establish a
      prediction model for temporomandibular joint (TMJ) disk perforation by
      constructing a nomogram. STUDY DESIGN: The study included a total of 282 joints
      in 274 patients. All patients underwent open TMJ surgery after obtaining magnetic
      resonance imaging (MRI), from 2005 to 2015. The presence or absence of disk
      perforation was confirmed during the operation. Patients were classified into 2
      groups: perforation and nonperforation groups. We investigated demographic data
      and the characteristics of the disk, joint space, and bone on MRI. A logistic
      regression analysis was performed to analyze risk factors. A nomogram was
      constructed and validated internally and externally. RESULTS: Risk factors for
      disk perforation were increased age, disk shape (eyeglass or amorphous), low bone
      marrow signal, abnormal joint space, and 2 or more bony changes in the condyle
      and fossa. The area under the receiver operating characteristic curve of the
      nomogram was 0.908 (95% confidence interval [CI] 0.869-0.946) in the internal
      validation and 0.889 (95% CI 0.804-0.973) in the external validation with good
      suitability. CONCLUSIONS: We were able to predict the probability of disk
      perforation with analyzed risk factors and constructed a nomogram, which may be
      helpful in proper diagnosis and treatment.

PMID- 29574056
TI  - Combining a Toggle Switch and a Repressilator within the AC-DC Circuit Generates
      Distinct Dynamical Behaviors.
AB  - Although the structure of a genetically encoded regulatory circuit is an
      important determinant of its function, the relationship between circuit topology
      and the dynamical behaviors it can exhibit is not well understood. Here, we
      explore the range of behaviors available to the AC-DC circuit. This circuit
      consists of three genes connected as a combination of a toggle switch and a
      repressilator. Using dynamical systems theory, we show that the AC-DC circuit
      exhibits both oscillations and bistability within the same region of parameter
      space; this generates emergent behaviors not available to either the toggle
      switch or the repressilator alone. The AC-DC circuit can switch on oscillations
      via two distinct mechanisms, one of which induces coherence into ensembles of
      oscillators. In addition, we show that in the presence of noise, the AC-DC
      circuit can behave as an excitable system capable of spatial signal propagation
      or coherence resonance. Together, these results demonstrate how combinations of
      simple motifs can exhibit multiple complex behaviors.

PMID- 29574058
TI  - Replacing zoledronic acid with denosumab is a risk factor for developing
      osteonecrosis of the jaw.
AB  - OBJECTIVE: Intravenous zoledronic acid (ZA) is often replaced with subcutaneous
      denosumab in patients with bone metastatic cancer. Despite their different
      pharmacologic mechanisms of action, both denosumab and ZA are effective in bone
      metastasis but cause osteonecrosis of the jaw (ONJ) as a side effect. ZA persists
      in the body almost indefinitely, whereas denosumab does not persist for long
      periods. This study evaluated the risks of developing ONJ when replacing ZA with
      denosumab. STUDY DESIGN: In total, 161 Japanese patients administered ZA for bone
      metastatic cancer were enrolled in this single-center, retrospective,
      observational study. The risk of developing ONJ was evaluated by logistic
      regression analysis using the following factors: age, gender, cancer type,
      angiogenesis inhibitors, steroids, and replacement of ZA with denosumab. RESULTS:
      Seventeen patients (10.6%) developed ONJ. Multiple regression analysis indicated
      a significant difference in rate of ONJ associated with replacement of ZA with
      denosumab (odds ratio = 3.81; 95% confidence interval 1.04-13.97; P = .043).
      CONCLUSIONS: Replacing ZA with denosumab is a risk factor for the development of
      ONJ. Both binding of bisphosphonate to bone and receptor activator of nuclear
      factor-kappa B ligand inhibition could additively increase the risk of ONJ. We
      bring the replacement of ZA with denosumab to the attention of clinical
      oncologists.

PMID- 29574059
TI  - "Tricyclic antidepressants and appropriate and inappropriate medications in the
      geriatric population"-comments.

PMID- 29574060
TI  - Radiculomegaly: a case report of this rare dental finding with review of the
      associated oculo-facio-cardio-dental syndrome.
AB  - BACKGROUND: Radiculomegaly, or root gigantism, is a rare dental abnormality with
      important clinical implications. It is highly specific for oculo-facio-cardio
      dental (OFCD) syndrome, which places dentists at the forefront of diagnosis of
      this syndrome. Only 1 case of nonsyndromic radiculomegaly has been reported in
      the literature since the description of OFCD syndrome in 1996. We present the
      second confirmed, nonsyndromic/nonfamilial case and review the literature for
      dental treatments in patients with this dental finding. STUDY DESIGN: A review of
      the English language literature was performed in PubMed for patients with
      radiculomegaly or OFCD syndrome. Teeth affected by radiculomegaly, gender,
      orodental findings, presence of OFCD syndrome, and dental treatment methods were
      recorded. RESULTS: Sixty-seven cases of radiculomegaly and 92 cases of OFCD
      syndrome were found in the literature. Only 1 confirmed case of
      nonsyndromic/nonfamilial radiculomegaly had been reported previously. Ten reports
      described dental treatment or treatment plan details, and even fewer included
      specific methods. CONCLUSIONS: Because dental anomalies, especially
      radiculomegaly, are a primary feature of OFCD syndrome, dentists should be aware
      of the clinical and radiographic features. Radiculomegaly poses a distinct
      challenge to dentists, and reports of dental therapy provided to these patients
      are sparse. Early diagnosis of the syndrome may prevent dental challenges and
      improve prognosis.

PMID- 29574061
TI  - Identification and characterization of two novel superantigens among
      Staphylococcus aureus complex.
AB  - Staphylococcal enterotoxins (SEs), also known as superantigens, play a very
      important role in infections and food poisoning caused by Staphylococcus aureus.
      Recently, S. argenteus and S. schweitzeri were recognized as novel species
      closely related to S. aureus. In this study of these three species, it was found
      that two putative SE genes were located upstream of some vSabeta pathogenicity
      islands and the deduced amino acid sequences showed < 65.3% identity with those
      of known SEs. The related proteins, designated staphylococcal enterotoxin-like
      toxin 26 (SEl26) and 27 (SEl27), were identified and characterized among the
      three species. The mRNAs encoding SEl26 and SEl27 were expressed during all the
      growth phases. Recombinant SEl26 and SEl27 exhibited superantigenic activity in
      human peripheral blood mononuclear cells and mouse splenocytes by examining cell
      proliferation and cytokine production. Interestingly, these two genes were
      present universally in S. argenteus sequence type 2250 with clinical importance.
      Meanwhile, SEl27 variants from different species showed differential sensitivity
      to human peripheral blood mononuclear cells, which corresponded to the primary
      bacterial species hosts. It was demonstrated from these results that SEl26 and
      SEl27 were characterized to be two novel SE toxins and some SEs evolved along
      with the bacteria when the organisms adapted the hosts' immune systems.

PMID- 29574063
TI  - Connective tissue growth factor (CTGF) from basics to clinics.
AB  - Connective tissue growth factor, also known as CCN2, is a cysteine-rich
      matricellular protein involved in the control of biological processes, such as
      cell proliferation, differentiation, adhesion and angiogenesis, as well as
      multiple pathologies, such as tumor development and tissue fibrosis. Here, we
      describe the molecular and biological characteristics of CTGF, its regulation and
      various functions in the spectrum of development and regeneration to fibrosis. We
      further outline the preclinical and clinical studies concerning compounds
      targeting CTGF in various pathologies with the focus on heart, lung, liver,
      kidney and solid organ transplantation. Finally, we address the advances and
      pitfalls of translational fibrosis research and provide suggestions to move
      towards a better management of fibrosis.

PMID- 29574062
TI  - Hyaluronan in inflammatory bowel disease: Cross-linking inflammation and
      coagulation.
AB  - Hyaluronan, a major extracellular matrix component, is an active participant in
      many disease states, including inflammatory bowel disease (IBD). The synthesis of
      this dynamic polymer is increased at sites of inflammation. Hyaluronan together
      with the enzymes responsible for its synthesis, degradation, and its binding
      proteins, directly modulates the promotion and resolution of disease by
      controlling recruitment of immune cells, by release of inflammatory cytokines,
      and by balancing hemostasis. This review discusses the functional significance of
      hyaluronan in the cells and tissues involved in inflammatory bowel disease
      pathobiology.

PMID- 29574064
TI  - Population monitoring for drug-resistant tuberculosis: is genomics the answer?

PMID- 29574066
TI  - Impaired Ca2+ handling in resistance arteries from genetically obese Zucker rats:
      Role of the PI3K, ERK1/2 and PKC signaling pathways.
AB  - The impact of obesity on vascular smooth muscle (VSM) Ca2+ handling and
      vasoconstriction, and its regulation by the phosphatidylinositol 3-kinase (PI3K),
      mitogen activated protein kinase (MAPK) and protein kinase C (PKC) were assessed
      in mesenteric arteries (MA) from obese Zucker rats (OZR). Simultaneous
      measurements of intracellular Ca2+ ([Ca2+]i) and tension were performed in MA
      from OZR and compared to lean Zucker rats (LZR), and the effects of selective
      inhibitors of PI3K, ERK-MAPK kinase and PKC were assessed on the functional
      responses of VSM voltage-dependent L-type Ca2+ channels (CaV1.2). Increases in
      [Ca2+]i induced by alpha1-adrenoceptor activation and high K+ depolarization were
      not different in arteries from LZR and OZR although vasoconstriction was enhanced
      in OZR. Blockade of the ryanodine receptor (RyR) and of Ca2+ release from the
      sarcoplasmic reticulum (SR) markedly reduced depolarization-induced Ca2+
      responses in arteries from lean but not obese rats, suggesting impaired Ca2+
      induced Ca2+ release (CICR) from SR in arteries from OZR. Enhanced Ca2+ influx
      after treatment with ryanodine was abolished by nifedipine and coupled to up
      regulation of CaV1.2 channels in arteries from OZR. Increased activation of ERK
      MAPK and up-regulation of PI3Kdelta, PKCbeta and delta isoforms were associated
      to larger inhibitory effects of PI3K, MAPK and PKC blockers on VSM L-type channel
      Ca2+ entry in OZR. Changes in arterial Ca2+ handling in obesity involve SR Ca2+
      store dysfunction and enhanced VSM Ca2+ entry through L-type channels, linked to
      a compensatory up-regulation of CaV1.2 proteins and increased activity of the ERK
      MAPK, PI3Kdelta and PKCbeta and delta, signaling pathways.

PMID- 29574067
TI  - Structure-kinetic relationship studies of cannabinoid CB2 receptor agonists
      reveal substituent-specific lipophilic effects on residence time.
AB  - A decade ago, the drug-target residence time model has been (re-)introduced,
      which describes the importance of binding kinetics of ligands on their protein
      targets. Since then, it has been applied successfully for multiple protein
      targets, including GPCRs, for the development of lead compounds with slow
      dissociation kinetics (i.e. long target residence time) to increase in vivo
      efficacy or with short residence time to prevent on-target associated side
      effects. To date, this model has not been applied in the design and
      pharmacological evaluation of novel selective ligands for the cannabinoid CB2
      receptor (CB2R), a GPCR with therapeutic potential in the treatment of tissue
      injury and inflammatory diseases. Here, we have investigated the relationships
      between physicochemical properties, binding kinetics and functional activity in
      two different signal transduction pathways, G protein activation and beta
      arrestin recruitment. We synthesized 24 analogues of 3-cyclopropyl-1-(4-(6-((1,1
      dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazoleidine-2,4
      dione (LEI101), our previously reported in vivo active and CB2R-selective
      agonist, with varying basicity and lipophilicity. We identified a positive
      correlation between target residence time and functional potency due to an
      increase in lipophilicity on the alkyl substituents, which was not the case for
      the amine substituents. Basicity of the agonists did not show a relationship with
      affinity, residence time or functional activity. Our findings provide important
      insights about the effects of physicochemical properties of the specific
      substituents of this scaffold on the binding kinetics of agonists and their CB2R
      pharmacology. This work therefore shows how CB2R agonists can be designed to have
      optimal kinetic profiles, which could aid the lead optimization process in drug
      discovery for the study or treatment of inflammatory diseases.

PMID- 29574065
TI  - Genetic sequencing for surveillance of drug resistance in tuberculosis in highly
      endemic countries: a multi-country population-based surveillance study.
AB  - BACKGROUND: In many countries, regular monitoring of the emergence of resistance
      to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing
      for drug susceptibility. We therefore evaluated the use of genetic sequencing for
      surveillance of drug resistance in tuberculosis. METHODS: Population-level
      surveys were done in hospitals and clinics in seven countries (Azerbaijan,
      Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to
      evaluate the use of genetic sequencing to estimate the resistance of
      Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin,
      moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug,
      we assessed the accuracy of genetic sequencing by a comparison of the adjusted
      prevalence of resistance, measured by genetic sequencing, with the true
      prevalence of resistance, determined by phenotypic testing. FINDINGS: Isolates
      were taken from 7094 patients with tuberculosis who were enrolled in the study
      between November, 2009, and May, 2014. In all tuberculosis cases, the overall
      pooled sensitivity values for predicting resistance by genetic sequencing were
      91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA,
      and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA
      (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin
      resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin
      resistance). For nearly all drugs and in most settings, there was a large overlap
      in the estimated prevalence of drug resistance by genetic sequencing and the
      estimated prevalence by phenotypic testing. INTERPRETATION: Genetic sequencing
      can be a valuable tool for surveillance of drug resistance, providing new
      opportunities to monitor drug resistance in tuberculosis in resource-poor
      countries. Before its widespread adoption for surveillance purposes, there is a
      need to standardise DNA extraction methods, recording and reporting nomenclature,
      and data interpretation. FUNDING: Bill & Melinda Gates Foundation, United States
      Agency for International Development, Global Alliance for Tuberculosis Drug
      Development.

PMID- 29574068
TI  - Natural product toosendanin reverses the resistance of human breast cancer cells
      to adriamycin as a novel PI3K inhibitor.
AB  - Adriamycin (ADM) is a commonly used drug in clinical breast cancer treatment.
      However, some breast cancer types or breast cancers subjected to repeated ADM
      exposure develop strong resistance to ADM thus limiting its clinical efficacy. In
      this study, we found for the first time that toosendanin (TSN), a triterpenoid
      extracted from the traditional Chinese medicine Melia toosendan Sieb et Zucc,
      could successfully reverse adriamycin resistance in human breast cancer cells.
      Immunofluorescence and HPLC analysis demonstrated that TSN promoted adriamycin
      accumulation in breast cancer cells, especially in the nucleus. Furthermore, TSN
      could significantly reduce ABCB1 expression. We then found that TSN was capable
      of suppressing adriamycin-induced Akt phosphorylation, probably due to
      downregulation of the PI3K catalytic subunits P110alpha and P110beta, and
      inhibition of DNA-PKcs. Importantly, the inhibitory effect of TSN on PI3K
      P110alpha and P110beta expression was specifically observed in breast cancer
      cells but not in normal human cells. Moreover, TSN significantly potentiated the
      anti-cancer effect of ADM in the 4T1 breast cancer model and its inhibition rate
      was nearly 90%. Thus, TSN could be used as a novel PI3K inhibitor to reverse
      breast cancer resistance. The combination of ADM and TSN may represent a useful
      strategy for human breast cancer therapy.

PMID- 29574069
TI  - Forskolin improves sensitivity to doxorubicin of triple negative breast cancer
      cells via Protein Kinase A-mediated ERK1/2 inhibition.
AB  - Triple negative breast cancer (TNBC) is an invasive, metastatic, highly
      aggressive tumor. Cytotoxic chemotherapy represents the current treatment for
      TNBC. However, relapse and chemo-resistance are very frequent. Therefore, new
      therapeutic approaches that are able to increase the sensitivity to cytotoxic
      drugs are needed. Forskolin, a natural cAMP elevating agent, has been used for
      several centuries in medicine and its safeness has also been demonstrated in
      modern studies. Recently, forskolin is emerging as a possible novel molecule for
      cancer therapy. Here, we investigate the effects of forskolin on the sensitivity
      of MDA-MB-231 and MDA-MB-468 TNBC cells to doxorubicin through MTT assay, flow
      cytometry-based assays (cell-cycle progression and cell death), cell number
      counting and immunoblotting experiments. We demonstrate that forskolin strongly
      enhances doxorubicin-induced antiproliferative effects by cell death induction.
      Similar effects are observed with IBMX and isoproterenol cAMP elevating agents
      and 8-Br-cAMP analog, but not by using 8-pCPT-2'-O-Me-cAMP Epac activator. It is
      important to note that the forskolin-induced potentiation of sensitivity to
      doxorubicin is accompanied by a strong inhibition of ERK1/2 phosphorylation, is
      mimicked by ERK inhibitor PD98059 and is prevented by pre-treatment with Protein
      Kinase A (PKA) and adenylate cyclase inhibitors. Altogether, our data indicate
      that forskolin sensitizes TNBC cells to doxorubicin via a mechanism depending on
      the cAMP/PKA-mediated ERK inhibition. Our findings sustain the evidence of
      anticancer activity mediated by forskolin and encourage the design of future in
      vivo/clinical studies in order to explore forskolin as a doxorubicin sensitizer
      for possible use in TNBC patients.

PMID- 29574070
TI  - Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia
      of metabolic syndrome: Quantity vs quality over time and implication of CETP.
AB  - BACKGROUND: Statins impact the metabolism, concentrations, composition, and
      function of circulating lipoproteins. OBJECTIVE: We evaluated time course
      relationships between statin-mediated reduction in atherogenic apolipoprotein B
      (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI
      containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic
      syndrome. METHODS: Insulin-resistant, hypertriglyceridemic, hypercholesterolemic,
      obese males (n = 12) were treated with pitavastatin (4 mg/d) and response
      evaluated at 6, 42, and 180 days. RESULTS: Reduction in low-density lipoprotein
      (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42
      days (-38%, -32%, and -35%, respectively); rapid reduction equally occurred in
      remnant cholesterol, ApoCII, CIII, and E levels (day 6; -35%, -50%, -23%, and 
      26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated
      at baseline and were markedly reduced on treatment (-29% vs total LDL mass).
      Cholesteryl ester (CE) transfer protein activity and mass decreased progressively
      (-18% and -16%, respectively); concomitantly, TG depletion (up to -49%) and CE
      enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations
      with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from
      LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was
      preferentially depleted from LpAI:AII-rich particles on treatment. CONCLUSION:
      Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer
      protein-mediated normalization of the HDL CE/TG core lags markedly behind
      subacute reduction in elevated levels of atherogenic ApoB-containing
      lipoproteins. Normalization of the HDL neutral lipid core is consistent with
      enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic
      marker of perturbed HDL metabolism in insulin-resistant states, equally allowing
      monitoring of statin impact on HDL metabolism, structure, and function.

PMID- 29574071
TI  - Poor attainment of lipid targets in patients with symptomatic peripheral artery
      disease.
AB  - BACKGROUND: Patients with peripheral artery disease (PAD) are at very high risk
      of future cardiovascular (CV) events. Strict lipid-lowering therapy is
      recommended. However, data on target level attainment are scarce. OBJECTIVE: The
      objective of the study was to investigate guideline equitable lipid lowering in a
      large observational study of symptomatic PAD patients. METHODS: Single-center
      observational study including 1109 patients with symptomatic PAD planned for
      revascularization at a tertiary university center. Between 2010 and 2017,
      guideline target level attainment trends over time and the association of statin
      therapy with CV mortality were analyzed. RESULTS: Atorvastatin (52.3%) and
      rosuvastatin (23.5%) were the most frequently prescribed statins and amounted to
      an average simvastatin equivalent of 52 mg/d. Attainment rates of low-density
      lipoprotein cholesterol (LDL-C) and of non-high-density lipoprotein cholesterol
      goals were as low as 27% and 33%, respectively. Although there was a significant
      improvement of LDL-C from 2010 to 2017 (mean LDL-C 110 vs 80 mg/dL, P < .0001 for
      trend), attainment remained poor, that is, only 42% in 2016 and 45% in 2017
      achieved the <70 mg/dL goal. CV mortality was significantly lower (4% vs 11%, P <
      .01) in statin-treated patients over a median follow-up period of 50 +/- 26
      months. CONCLUSION: There is a remarkable undertreatment of LDL-C and non-high
      density lipoprotein cholesterol in patients with symptomatic PAD, although LDL-C
      decreased significantly from 2010 to 2017. As statin treatment was associated
      with a reduced CV mortality rate, our findings call for an increased awareness in
      clinical lipidology regarding symptomatic PAD patients.

PMID- 29574072
TI  - Recovery of lipid metabolic alterations in hepatitis C patients after viral
      clearance: Incomplete restoration with accelerated omega-oxidation.
AB  - BACKGROUND: How hepatitis C virus (HCV)-associated lipid metabolic alterations
      recover after sustained virological response (SVR) remains elusive. OBJECTIVE:
      The aforementioned recovery pattern was investigated. METHODS: In a prospective
      cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV
      therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent
      paired-serum liquid chromatography-tandem mass spectrometry analyses before and
      24 weeks after therapy. Subjects without CHC served as controls (n = 100).
      RESULTS: CHC patients had lower baseline lipid levels than controls. Among CHC
      patients, pre-therapy total cholesterol levels were positively associated with
      HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2
      patients. Repeated measures analysis of variance of CHC patients showed that
      lathosterol, lanosterol, total hydroxysphingomyelin, and total
      phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine
      (indicators of omega-oxidation) and pre-beta-lipoprotein ratios elevated 24 weeks
      after therapy compared with the levels before therapy. Levels of total
      lysophosphatidylcholines and alpha- and beta-lipoprotein ratios decreased.
      Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels,
      particularly in G2 and male patients, who had broader spectra of altered
      phosphatidylcholines and acylcarnitines than G1 and female patients,
      respectively. Compared with controls, CHC patients had higher post-therapy levels
      of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total
      dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels.
      CONCLUSIONS: At 24 weeks after therapy, accelerated cholesterol biosynthesis,
      hepatic lipid export, omega-oxidation, and decreased systemic inflammation were
      noted in CHC patients with SVR, with greater efficiency in G2 and male patients.
      Regardless, HCV-associated lipid metabolic alterations required >24 weeks for
      restoration or were incompletely reversible after SVR.

PMID- 29574073
TI  - Selective prescribing of statins and the risk of mortality, hospitalizations, and
      falls in aged care services.
AB  - BACKGROUND: Compared to randomized controlled trials, nonexperimental studies
      often report larger survival benefits but higher rates of adverse events for
      statin use vs nonuse. OBJECTIVE: We compared characteristics of statin users and
      nonusers living in aged care services and evaluated the relationships between
      statin use and all-cause mortality, all-cause and fall-related hospitalizations,
      and number of falls during a 12-month follow-up. METHODS: A prospective cohort
      study of 383 residents aged >=65 years was conducted in six Australian aged care
      services. Data were obtained from electronic medical records and medication
      charts and through a series of validated assessments. RESULTS: The greatest
      differences between statin users and nonusers were observed in activities of
      daily living, frailty, and medication use (absolute standardized difference
      >0.40), with users being less dependent and less frail but using a higher number
      of medications. Statin use was associated with a decreased risk of all-cause
      mortality (adjusted hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.37
      0.93) and hospitalizations (HR 0.67, 95% CI 0.46-0.98). After exclusion of
      residents unable to sit or stand, statin use was associated with a nonsignificant
      increase in the risk of fall-related hospitalizations (HR 1.47, 95% CI 0.80-2.68)
      but with a lower incidence of falls (incidence rate ratio 0.67, 95% CI 0.47
      0.96). CONCLUSIONS: The observed associations between statin use and the outcomes
      may be largely explained by selective prescribing and deprescribing of statins
      and variation in likelihood of hospitalization based on consideration of each
      resident's clinical and frailty status. Randomized deprescribing trials are
      needed to guide statin prescribing in this setting.

PMID- 29574074
TI  - Prevalence, management, and outcomes of familial hypercholesterolemia in patients
      with acute coronary syndromes in the Arabian Gulf.
AB  - BACKGROUND: Information on the epidemiology of familial hypercholesterolemia (FH)
      in the Arabian Gulf region, which has an elevated rate of consanguinity and type
      II diabetes, is scarce. OBJECTIVES: To assess the prevalence of FH, its
      management, and impact on atherosclerotic cardiovascular disease (ASCVD) outcomes
      in a multicenter cohort of Arabian Gulf patients with acute coronary syndrome
      (ACS). METHODS: Patients (N = 3224) hospitalized with ACS were studied. FH was
      diagnosed using the Dutch Lipid Clinic Network criteria. A composite endpoint of
      nonfatal myocardial infarction, stroke, transient ischemic attack, and mortality
      between the "probable/definite" and the "unlikely" FH patients was assessed after
      1 year. Analyses were performed using univariate and multivariate statistical
      techniques. RESULTS: At admission, the proportion of "probable/definite",
      "possible", and "unlikely" FH in ACS patients was 3.7% (n = 119), 28% (n = 911),
      and 68% (n = 2194), respectively. Overall, 54% (n = 1730) of patients had
      diabetes, whereas 24% (n = 783) were current smokers. The "probable/definite" FH
      group was younger (50 vs 63 years; P < .001), had a greater prevalence of early
      coronary disease (38% vs 8.8%; P < .001), and previous statin use (87% vs 57%; P
      < .001) when compared with the "unlikely" FH group. After 1 year, the
      "probable/definite" FH cohort had worse lipid control (13% vs 23%; P < .001) and
      presented with a greater association with the composite ASCVD endpoint when
      compared with the "unlikely" FH group (odds ratio: 1.85; 95% confidence interval:
      1.01-3.38; P = .047) after multivariable adjustment. CONCLUSIONS: In Arabian Gulf
      citizens, FH was common in ACS patients, was undertreated, and was associated
      with a worse 1-year prognosis.

PMID- 29574076
TI  - Detection and quantitation of irisin in human cerebrospinal fluid by tandem mass
      spectrometry.
AB  - The myokine irisin can cross the blood brain barrier and act as a neurokine to
      protect brain function during endurance exercise. However, the mechanism of
      transport from the blood to cerebrospinal fluid is unknown. Irisin has been
      detected in rodent and human brain and human cerebrospinal fluid by using
      commercial antibodies and enzyme linked immunosorbent assay kits. However, as
      human FNDC5 has an atypical translation start codon, some studies have questioned
      the specificity of commercial antibodies. Recently, human irisin was identified
      and quantitated in plasma by using mass spectrometry. We investigated whether
      there was irisin in human cerebrospinal fluid and an irisin concentration
      gradient between in human cerebrospinal fluid and paired plasma. An irisin
      peptide was identified and quantitated by using mass spectrometry with control
      peptides enriched with heavy stable isotopes as internal standards. Quantitative
      mass spectrometry identified the presence of irisin in human cerebrospinal fluid.
      The internal irisin peptides were modified to the deamidated asparagine form
      after deglycosylation. The unmodified internal irisin peptides were not found in
      CSF and irisin concentration was approximately 0.26-1.86 ng/ml in men over 80
      years of age with various diseases. However, the parallel reaction monitoring
      (PRM) elution profiles of both modified and unmodified internal irisin peptides
      were not found in paired plasma samples. These data unequivocally demonstrated
      the presence of the glycosylated form of irisin in human cerebrospinal fluid.
      There were significant individual differences in men over 80 years of age with
      diseases. However, irisin was not detected in plasma samples by using mass
      spectrometry.

PMID- 29574075
TI  - Relationship between "LDL-C", estimated true LDL-C, apolipoprotein B-100, and
      PCSK9 levels following lipoprotein(a) lowering with an antisense oligonucleotide.
AB  - BACKGROUND: The laboratory measurement of "low-density lipoprotein cholesterol
      (LDL-C)" includes the cholesterol content of lipoprotein(a) (Lp(a)-C). OBJECTIVE:
      To estimate the "true" LDL-C in relation to changes in apolipoprotein B-100 (apoB
      100) and assess changes in proprotein convertase subtilisin/kexin 9 (PCSK9)
      levels in patients with elevated Lp(a) treated with IONIS-APO(a)Rx. METHODS: A
      pooled placebo group (n = 29), and cohort A (n = 24, baseline Lp(a) 50-175 mg/dL)
      and cohort B (n = 8, baseline Lp(a) > 175 mg/dL) treated with IONIS-APO(a)Rx were
      studied. Lp(a) particle number, ultracentrifugation-measured "LDL-C", apoB-100,
      total PCSK9, and lipoprotein-associated PCSK9 (PCSK9-Lp(a), PCSK9-apoB, PCSK9
      apoAI) were measured. Lp(a)-cholesterol (Lp(a)-C) and LDL-C corrected for Lp(a)-C
      (LDL-Ccorr) were calculated. RESULTS: Baseline mean (standard deviation) "LDL-C"
      was 120 (42), 128 (45), and 112 (39) mg/dL in placebo, cohorts A and B,
      respectively, whereas LDL-Ccorr was 86 (48), 96 (43), and 57 (37) mg/dL (P < .001
      compared with placebo), representing 28%, 25%, and 50% lower levels than "LDL-C".
      Following IONIS-APO(a)Rx treatment at day 85/99, Lp(a) particle number and Lp(a)
      C decreased -66.8% and -71.6%, apoB-100 -10.3% and -17.5%, "LDL-C" -11.8% and 
      22.7%, (P < .001 for all vs placebo), whereas LDL-Ccorr increased +10.4% (P =
      .66) and +49.9% (P < .001) in cohorts A and B, respectively. Total PCSK9 did not
      change but PCSK9-Lp(a) decreased with IONIS-APO(a)Rx vs placebo (-39.0% vs +8.4%,
      P < .001). CONCLUSION: LDL-Ccorr is lower than laboratory "LDL-C" in patients
      with elevated Lp(a). Following apolipoprotein(a) inhibition and decline in Lp(a)
      and Lp(a)-C, the decline in apoB-100 is consistent with the notion that LDL
      devoid of apo(a) is cleared faster than Lp(a). These types of analyses may
      provide insights into the mechanisms of drugs affecting Lp(a) levels in clinical
      trials.

PMID- 29574077
TI  - Wheat amylase-trypsin inhibitors exacerbate intestinal and airway allergic immune
      responses in humanized mice.
AB  - BACKGROUND: Amylase-trypsin inhibitors (ATIs) in wheat and related cereals are
      potent activators of myeloid innate immune cells via engagement of TLR4.
      Furthermore, ATIs have been shown to serve as adjuvants in experimental
      intestinal inflammatory diseases. OBJECTIVE: The aim of this study was to analyze
      whether ATIs are also modifiers of allergic inflammation. METHODS: Therefore,
      CD4+ T cells from donors sensitized to grass or birch pollen were stimulated with
      autologous allergen-pulsed dendritic cells in the presence or absence of ATIs or
      the control storage protein zein from corn. To analyze allergen-induced gut and
      lung inflammation, immunodeficient mice were engrafted with PBMCs from these
      allergic donors plus the respective allergen, and fed with selected diets. Three
      weeks later, inflammation was induced by rectal or intranasal allergen challenge
      and monitored by mini endoscopy or airway hyperreactivity, respectively. RESULTS:
      Allergen-specific T-cell proliferation and cytokine production was significantly
      exacerbated by ATIs and not by zein. In vivo, allergen-specific human IgE level
      was strongly elevated in sera of mice receiving an ATI-containing diet compared
      with mice that were fed gluten-free and thus ATI-free diet. Importantly, allergen
      induced IgE-dependent colitis and airway hyperreactivity were also enhanced in
      ATI-fed mice. Gut inflammation was further increased in mice receiving an
      additional ATI injection and even detectable in the absence of the aeroallergen,
      whereas zein had no such effect. Injection of anti-human TLR4 mAbs or the anti
      human IgE mAb omalizumab completely abolished ATI-induced allergic inflammation.
      CONCLUSIONS: These results underline that wheat ATIs are important nutritional
      activators and adjuvants of allergy, which might be exploited for nutritional
      therapeutic strategies.

PMID- 29574078
TI  - A novel dressing for the combined delivery of platelet lysate and vancomycin
      hydrochloride to chronic skin ulcers: Hyaluronic acid particles in alginate
      matrices.
AB  - The aim of the present work was to develop a medication allowing for the combined
      delivery of platelet lysate (PL) and an anti-infective model drug, vancomycin
      hydrochloride (VCM), to chronic skin ulcers. A simple method was set up for the
      preparation of hyaluronic acid (HA) core-shell particles, loaded with PL and
      coated with calcium alginate, embedded in a VCM containing alginate matrix. Two
      different CaCl2 concentrations were investigated to allow for HA/PL core-shell
      particle formation. The resulting dressings were characterized for mechanical and
      hydration properties and tested in vitro (on fibroblasts) and ex-vivo (on skin
      biopsies) for biological activity. They were found of sufficient mechanical
      strength to withstand packaging and handling stress and able to absorb a high
      amount of wound exudate and to form a protective gel on the lesion area. The
      CaCl2 concentration used for shell formation did not affect VCM release from the
      alginate matrix, but strongly modified the release of PGFAB (chosen as
      representative of growth factors present in PL) from HA particles. In vitro and
      ex vivo tests provided sufficient proof of concept of the ability of dressings to
      improve skin ulcers healing.

PMID- 29574079
TI  - New fluorescence-based high-throughput screening assay for small molecule
      inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2).
AB  - Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated
      DNA damages and causes resistance to TOP2-targeted cancer therapy. Inhibiting
      TDP2 could sensitize cancer cells toward TOP2 inhibitors. However, potent TDP2
      inhibitors with favorable physicochemical properties are not yet reported.
      Therefore, there is a need to search for novel molecular scaffolds capable of
      inhibiting TDP2. We report herein a new simple, robust, homogenous mix-and-read
      fluorescence biochemical assay based using humanized zebrafish TDP2 (14M_zTDP2),
      which provides biochemical and molecular structure basis for TDP2 inhibitor
      discovery. The assay was validated by screening a preselected library of 1600
      compounds (Z' >= 0.72) in a 384-well format, and by running in parallel gel-based
      assays with fluorescent DNA substrates. This library was curated via virtual high
      throughput screening (vHTS) of 460,000 compounds from Chembridge Library, using
      the crystal structure of the novel surrogate protein 14M_zTDP2. From this primary
      screening, we selected the best 32 compounds (2% of the library) to further
      assess their TDP2 inhibition potential, leading to the IC50 determination of 10
      compounds. Based on the dose-response curve profile, pan-assay interference
      compounds (PAINS) structure identification, physicochemical properties and
      efficiency parameters, two hit compounds, 11a and 19a, were tested using a novel
      secondary fluorescence gel-based assay. Preliminary structure-activity
      relationship (SAR) studies identified guanidine derivative 12a as an improved hit
      with a 6.4-fold increase in potency over the original HTS hit 11a. This study
      highlights the importance of the development of combination approaches
      (biochemistry, crystallography and high throughput screening) for the discovery
      of TDP2 inhibitors.

PMID- 29574080
TI  - Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.
AB  - Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key
      polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora)
      possesses various health-promoting activities. To optimize its medicinal
      application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with
      emphases to identify the impacts from dose and repeated dosing on its major
      pharmacokinetic parameters. Plasma ATE levels were monitored by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single
      intravenous administration (2 mg/kg), plasma levels of ATE declined through an
      apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its
      non-linear disposition, which could be described by the Michaelis-Menten model.
      Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose
      was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT0
      >last), higher dose-normalized maximal plasma concentration (Cmax/Dose) and
      exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral
      administration of ATE at 15 mg/kg caused its accelerated elimination and the
      plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15
      mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time
      dependent pharmacokinetics, caution is needed in the medicinal applications of
      ATE and/or black ginger.

PMID- 29574081
TI  - Effects of enzymatic degradation on dynamic mechanical properties of the vitreous
      and intravitreal nanoparticle mobility.
AB  - Intravitreal mobility of nanocarriers may have implications on the efficacy of
      the encapsulated drug in the treatment of vitreo-retinal diseases, with any
      changes in the integrity of the vitreous microstructure influencing nanoparticle
      biodistribution. This study investigated enzymatically digested vitreous models
      to mimic the aging eye. Collagenase, hyaluronidase, or trypsin was employed to
      selectively digest the structural components of the vitreous. Physical properties
      of digested bovine vitreous were initially assessed via texture analysis and
      oscillatory shear testing. Morphological changes in bovine vitreous
      microstructure were visualized by scanning electron microscopy and diffusion
      dynamics of hyaluronic acid coated nanoparticles through degraded porcine and
      bovine vitreous were examined using fluorescence spectroscopy and multiple
      particle tracking microscopy, respectively. After enzymatic treatment, the
      vitreous liquefied and its dynamic mechanical properties significantly changed
      with a decrease in stiffness and an increase in damping capacity. Micrographs
      confirmed specific digestion of each of the structural vitreous components.
      Furthermore, enzymatic degradation reduced steric hindrance and enhanced
      convective flow within the vitreous, resulting in increased intravitreal
      nanoparticle mobility which could alter the drug pharmacokinetics.

PMID- 29574083
TI  - An in vitro and in silico identification of antibiofilm small molecules from
      seawater metaclone SWMC166 against Vibrio cholerae O1.
AB  - This study aimed to determine the antibiofilm activity of seawater microbes
      against Vibrio cholerae (VCO1) through functional metagenomics approach. A
      metagenomic library was constructed from Palk Bay seawater and the library was
      screened to identify the biofilm inhibitory metaclone. Metaclone SWMC166
      (harbouring ~30 kb metagenomic insert) was found to exhibit antibiofilm activity
      against VCO1. The biofilm inhibitory potential of partially purified ethyl
      acetate extract of SWMC166 (EA166) was further evaluated through microscopic
      studies and biochemical assays. Further, EA166 treated VCO1 divulged up
      regulation of genes involved in high cell density-mediated quorum sensing (QS)
      pathway which was analysed by real-time PCR. In order to identify the genes of
      interest (within ~30 kb insert), subcloning was performed through shotgun
      approach. Small molecules from positive subclones SC5 and SC8 were identified
      through HRLC-MS analysis. Resulted small molecules were docked against QS
      receptors of V. cholerae to identify the bioactive metabolites. Docking studies
      revealed that totally seven metabolites were able to interact with QS receptors
      that can possibly trigger the QS cascade and sequentially inhibit the biofilm
      formation and virulence factors of VCO1.

PMID- 29574084
TI  - Oculogyric crises in PLA2G6 associated neurodegeneration.

PMID- 29574085
TI  - Combined measurement of plasma cystatin C and low-density lipoprotein
      cholesterol: A valuable tool for evaluating progressive supranuclear palsy.
AB  - INTRODUCTION: Progressive supranuclear palsy (PSP) was previously thought as a
      cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density
      cholesterol lipoprotein-C (LDL-C) are known to play critical roles in
      Parkinsonism, it is unknown whether they can be used as markers to distinguish
      PSP patients from healthy subjects and to determine disease severity. METHODS: We
      conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of
      40 patients with PSP and 40 healthy age-matched controls. An extended battery of
      motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the
      Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental
      State Examination (MMSE), was used to evaluate the disease severity. Receiver
      operating characteristic (ROC) curves were adopted to assess the prognostic
      accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects.
      RESULTS: Patients with PSP exhibited significantly higher plasma levels of Cys C
      and lower LDL-C. The levels of plasma Cys C were positively and inversely
      correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C
      ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for
      the combination of Cys C and LDL-C yielded a better accuracy for distinguishing
      PSP from healthy subjects than the separate curves for each parameter.
      CONCLUSIONS: Plasma Cys C and LDL-C may be valuable screening tools for
      differentiating PSP from healthy subjects; while they could be useful for the PSP
      intensifies and severity evaluation. A better understanding of Cys C and LDL-C
      may yield insights into the pathogenesis of PSP.

PMID- 29574087
TI  - Factors associated with advanced-stage Merkel cell carcinoma at initial diagnosis
      and the use of radiation therapy: Results from the National Cancer Database.
AB  - BACKGROUND: The stage of disease at initial diagnosis and the use of radiation
      therapy (RT) are important determinants of survival in patients with Merkel cell
      carcinoma (MCC). OBJECTIVE: To define factors that are associated with advanced
      stage MCC at the time of initial diagnosis and the use of RT. METHODS: Cross
      sectional, retrospective analysis of patients with MCC registered in the National
      Cancer Database during the period from 2004 to 2013. RESULTS: A total of 11,917
      patients were identified; 3152 and 4586 patients were excluded from the staging
      and RT analyses, respectively, because of lack of available data. African
      American ethnicity (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.06
      2.10; P = .023), lack of medical insurance (OR, 2.15; 95% CI, 1.40-3.30; P <
      .001), Charlson-Deyo comorbidity score of at least 1 (OR, 1.21; 95% CI, 1.09
      1.34; P < .001), residence more than 26 miles from a treatment facility (OR,
      1.18; 95% CI, 1.03-1.35; P = .015), tumor located on the lower limb/hip (OR,
      1.59; 95% CI, 1.42-1.78; P < .001) or trunk (OR, 2.05; 95% CI, 1.81-2.33; P <
      .001), and poorly (OR, 2.57; 95% CI, 1.13-5.82; P = .024) or undifferentiated
      (OR, 3.11; 95% CI, 1.36-7.15; P = .007) tumor histology predicted advanced-stage
      MCC at the time of initial diagnosis. The use of RT was associated with Native
      American ethnicity (OR, 5.04; 95% CI, 1.10-22.99; P = .037), tumor size between
      1.5 and 2.7 cm (OR, 1.27; 95% CI, 1.10-1.47; P = .001), electing not to have
      surgery (OR, 2.77; 95% CI, 1.90-4.03; P < .001), positive postsurgical margins
      (OR, 1.39; 95% CI, 1.18-1.63; P < .001), and receiving treatment at a
      comprehensive cancer program (OR, 1.25; 95% CI, 1.03-1.50; P = .020).
      LIMITATIONS: Retrospective design limits generalizability of the results, and
      precise details of RT regimens utilized were not available. CONCLUSIONS: A number
      of factors are associated with advanced-stage MCC at initial diagnosis and the
      use of RT. Health care models should account for these factors, and efforts
      should be directed toward improving those that are modifiable.

PMID- 29574082
TI  - Impact of sex steroids and reproductive stage on sleep-dependent memory
      consolidation in women.
AB  - Age and sex are two of the three major risk factors for Alzheimer's disease (ApoE
      e4 allele is the third), with women having a twofold greater risk for Alzheimer's
      disease after the age of 75 years. Sex differences have been shown across a wide
      range of cognitive skills in young and older adults, and evidence supports a role
      for sex steroids, especially estradiol, in protecting against the development of
      cognitive decline in women. Sleep may also be a protective factor against age
      related cognitive decline, since specific electrophysiological sleep events (e.g.
      sleep spindle/slow oscillation coupling) are critical for offline memory
      consolidation. Furthermore, studies in young women have shown fluctuations in
      sleep events and sleep-dependent memory consolidation during different phases of
      the menstrual cycle that are associated with the levels of sex steroids. An under
      appreciated possibility is that there may be an important interaction between
      these two protective factors (sex steroids and sleep) that may play a role in
      daily fluctuations in cognitive processing, in particular memory, across a
      woman's lifespan. Here, we summarize the current knowledge of sex steroid
      dependent influences on sleep and cognition across the lifespan in women, with
      special emphasis on sleep-dependent memory processing. We further indicate gaps
      in knowledge that require further experimental examination in order to fully
      appreciate the complex and changing landscape of sex steroids and cognition.
      Lastly, we propose a series of testable predictions for how sex steroids impact
      sleep events and sleep-dependent cognition across the three major reproductive
      stages in women (reproductive years, menopause transition, and post-menopause).

PMID- 29574086
TI  - Cerebral gray matter volume losses in essential tremor: A case-control study
      using high resolution tissue probability maps.
AB  - INTRODUCTION: Essential tremor (ET) is increasingly recognized as a multi
      dimensional disorder with both motor and non-motor features. For this reason,
      imaging studies are more broadly examining regions outside the cerebellar motor
      loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized
      processing, adapted to high-resolution magnetic resonance imaging (MRI). We
      investigated cerebral GM volume loss in ET cases using automated segmentation of
      MRI T1-weighted images. METHODS: MRI was acquired on 47 ET cases and 36 controls.
      Automated segmentation and voxel-wise comparisons of volume were performed using
      Statistical Parametric Mapping (SPM) software. To improve upon standard
      protocols, the high-resolution International Consortium for Brain Mapping (ICBM)
      2009a atlas and tissue probability maps were used to process each subject image.
      Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH)
      vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was
      performed between ET with and without head tremor and controls. Age, sex, and
      Montreal Cognitive Assessment (MoCA) score were regressed out from each
      comparison. RESULTS: We were able to consistently identify regions of cerebral GM
      volume loss in ET and in ET subgroups in the posterior insula, superior temporal
      gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal
      regions. There were no significant increases in GM volume in ET in any
      comparisons with controls. CONCLUSION: This study, which uses improved
      methodologies, provides evidence that GM volume loss in ET is present beyond the
      cerebellum, and in fact, is widespread throughout the cerebrum as well.

PMID- 29574088
TI  - A 10-point plan to demonstrate the value of dermatology in the health care
      system.
AB  - In May 2017, the American Academy of Dermatology convened a Dermatology Specialty
      Summit, with representatives from 15 dermatology specialty societies, the
      American Board of Dermatology, and the Coalition of Skin Diseases in attendance.
      The Summit's goal was to identify opportunities to address and enhance the
      perception of dermatology in the House of Medicine, the role of data in the
      changing health care environment, and access to dermatologic care. Summit
      participants collectively identified a list of 10 action items that address
      opportunities in these areas of concern. These include active participation in
      the House of Medicine, increased interaction with and education of our primary
      care colleagues, efforts to support DataDerm, and creative ways to improve
      access.

PMID- 29574089
TI  - Trends in phototherapy utilization among Medicare beneficiaries in the United
      States, 2000 to 2015.
AB  - BACKGROUND: Phototherapy is a cost-effective treatment for many dermatoses, yet
      the emergence of alternative therapies such as biologics led many to think that
      phototherapy utilization was declining. OBJECTIVE: To characterize national,
      historical phototherapy utilization and costs among Medicare beneficiaries.
      METHODS: Longitudinal analysis of the Medicare Part B National Summary Data File
      from 2000 to 2015 for phototherapy billing codes. Geographic distribution of
      clinics and provider type obtained from the Medicare Provider Utilization and
      Payment Data for 2012 to 2015. RESULTS: The overall volume of phototherapy
      services billed to Medicare from 2000 to 2015 increased by 5% annually, from
      334,670 to 692,093. Ultraviolet B therapy comprised 77% of phototherapy volume,
      utilization of psoralen plus ultraviolet A therapy declined by 9% annually, and
      excimer laser services grew by 29% annually. The number of phototherapy clinics
      is increasing but remains concentrated in only 11% of US counties. Between 2012
      and 2015, dermatologists accounted for 92% of phototherapy volume. LIMITATIONS:
      Commercial payers and institutional claims (hospital-based physicians) are
      excluded. Clinical indications for phototherapy use are not reported in this
      database. CONCLUSION: Phototherapy utilization has grown, though the service mix
      has shifted toward ultraviolet B and laser excimer therapy and away from psoralen
      plus ultraviolet A therapy. Dermatologists manage most phototherapy. Uneven
      geographic distribution of phototherapy clinics limits access in nonurban areas,
      and further evaluation is needed to determine its impact on rural communities.

PMID- 29574090
TI  - How data can deliver for dermatology.

PMID- 29574091
TI  - Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a
      Colorectal Cancer Screening Population.
AB  - BACKGROUND & AIMS: The presence of specific single nucleotide polymorphisms
      (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC),
      called a genetic risk score (GRS). We investigated whether GRS can identify
      individuals with clinically relevant neoplasms in a screening colonoscopy
      population. METHODS: We derived a GRS based on 48 SNPs associated with CRC,
      identified in a comprehensive literature search. We obtained genetic data from
      1043 participants (50-79 years old) in a screening colonoscopy study in Germany,
      recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non
      advanced adenoma (NAAs), and 500 without neoplasms). Each participant was
      assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced
      neoplasms and NAA according to GRS was calculated by multiple logistic
      regression. Risk advancement periods were calculated. We replicated our findings
      using data from a subset of the Tennessee Colorectal Polyp Study. RESULTS: An
      increased GRS was associated with higher prevalence of advanced neoplasms, but
      not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and
      2.7-fold increase in risk, respectively, of advanced neoplasms compared to those
      in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence
      interval [CI], 0.76-1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70
      1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced
      neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and
      the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for
      medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was
      17.5 years (95% CI, 7.8-27.3). CONCLUSIONS: In a genetic analysis of participants
      in a CRC screening study in Germany, an increased GRS (based on CRC-associated
      SNPs) was associated with increased prevalence of advanced neoplasms. These
      findings might be used in defining risk-adapted screening ages.

PMID- 29574092
TI  - Plectin-1 Targeted Dual-modality Nanoparticles for Pancreatic Cancer Imaging.
AB  - BACKGROUND: Biomarker-targeted molecular imaging holds promise for early
      detection of pancreatic cancer. The aim of this study was to design and evaluate
      a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer
      imaging. METHODS: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N
      amino(polyethylene glycol) (DSPE-PEG-NH2)-modified superparamagnetic iron oxide
      (Fe3O4) nanoparticles (SPION) were conjugated with plectin-1 antibody and/or Cy7
      to create the multi-functional targeted nanoparticle targeted probe (Plectin
      SPION-Cy7) or non-targeted probe (SPION-Cy7). Pancreatic carcinoma cell lines
      expressing plectin-1 were cultured with the targeted or control probes and then
      were imaged using confocal laser scanning microscopy and magnetic resonance
      imaging (MRI). Accumulations of the nanoparticles in pancreatic tumor xenografted
      mice were determined by MRI and fluorescence imaging. RESULTS: In vitro optical
      imaging and MRI showed that the targeted nanoparticles were highly accumulated in
      MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells, which was
      further confirmed by Prussian blue staining. In vivo MRI showed a significant T2
      signal reduction. Prussian blue staining further confirmed that the plectin-1
      targeted nanoparticles were highly accumulated in the tumor mass but not in
      normal pancreatic tissues, or in the liver and kidney, and few nanoparticles were
      observed in the tumors of mice injected with SPION-Cy7. CONCLUSIONS: Our data
      demonstrate that plectin-1 targeted fluorescence and MR dual-functional
      nanoparticle can visualize pancreatic cancer, and it has great potential to be
      used with various imaging devices for pancreatic cancer detection.

PMID- 29574093
TI  - Alisma canaliculatum ethanol extract suppresses inflammatory responses in LPS
      stimulated macrophages, HCl/EtOH-induced gastritis, and DSS-triggered colitis by
      targeting Src/Syk and TAK1 activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alisma canaliculatum A.Braun & C.D.Bouche,
      distributed in Korea, Japan, China, and Taiwan, is a traditional medicine. In
      particular, the stem and root of Alisma canaliculatum A.Braun & C.D.Bouche are
      prescribed to relieve various inflammatory symptoms resulting from nephritis,
      cystitis, urethritis, and dropsy. AIM OF STUDY: However, the curative mechanism
      of Alisma canaliculatum A.Braun & C.D.Bouche with respect to inflammatory
      symptoms is poorly understood. In this study, the curative roles of this plant in
      various inflammatory conditions as well as its inhibitory mechanism were aimed to
      examine using an ethanol extract (Ac-EE). MATERIALS AND METHODS: Anti
      inflammatory effects of Ac-EE were evaluated in lipopolysaccharide (LPS)-induced
      macrophages in vitro and HCl/EtOH-stimulated mouse model of gastritis and DSS
      treated mouse model of colitis. To determine the potentially active anti
      inflammatory components in this extracts, we employed HPLC. We also used kinase
      assays, reporter gene assay, immunoprecipitation analysis and target enzyme
      overexpressing cell analysis to analyze the molecular mechanisms and the target
      molecules. RESULTS: This extract dose-dependently inhibited the production of
      nitric oxide (NO) and prostaglandin E2 (PGE2) from RAW264.7 cells and peritoneal
      macrophages activated by lipopolysaccharide (LPS). Additionally, Ac-EE
      ameliorated inflammatory symptoms resulting from gastritis and colitis. Ac-EE
      down-regulated the mRNA levels of inducible NO synthase (iNOS), tumor necrosis
      factor (TNF)-alpha, and cyclooxygenase-2 (COX-2). Ac-EE also blocked the nuclear
      translocation of nuclear factor (NF)-kappaB and activator protein (AP)- 1 in LPS
      stimulated RAW264.7 cells. By analyzing the target signaling molecules activating
      these transcription factors, we found that Src and Syk, as well as molecular
      association between TAK1 and mitogen-activated protein kinase kinase 4/7
      (MKK4/7), were targeted by Ac-EE. CONCLUSIONS: Our data suggest that the Ac-EE NF
      kappaB/AP-1-targeted anti-inflammatory potential is mediated by suppression of
      Src and Syk as well as the complex formation between TAK1 and its substrate
      proteins MKK4/7.

PMID- 29574094
TI  - Regulation of human dendritic cell immune functions by ion channels.
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells (APCs) able
      to induce both specific immunity and immune tolerance. Using information gathered
      from the tissue where they reside, DCs adjust their functional activity to ensure
      that protective immunity is favoured while unwanted or exaggerated immune
      responses are prevented. The remarkable ability of these cells to induce, enhance
      and orient the immune response, while at the same time maintaining self
      tolerance, makes them key players in the immune system. Despite the fact that the
      role of Ca2+ has been clearly established in human DC functions, the link between
      ion homeostasis, mainly Ca2+, and DC functions is not fully understood. After
      all, a growing number of works clearly show the role of SOCE and associated
      channels in the maturation step, and those of K+ channels in migration. This
      review highlights the key papers published over the past few years and summarizes
      prospects for the near future.

PMID- 29574095
TI  - Changes in uptake and cost of long-acting reversible contraceptive devices
      following the introduction of a new low-cost levonorgestrel IUD in Utah's Title X
      clinics: a retrospective review.
AB  - OBJECTIVE: The objective was to assess changes in long-acting reversible
      contraceptive (LARC) method uptake at Utah's Title X clinics before and after
      introduction of a new, low-cost levonorgestrel (LNG) 52mg IUD (Liletta(r)). STUDY
      DESIGN: We conducted a retrospective medical record review of LARC visits
      occurring at seven Title-X family planning clinics in Utah before the
      introduction of the low-cost LNG IUD (preintroduction period: 01/01/2014
      04/30/2015) and after (postintroduction period: 05/01/2015-03/31/2016). We ran
      segmented, interrupted time series ordinary least squares regression models using
      Newey-West standard errors to assess both the change in numbers of women
      initiating any LARC method and the average payment amount per LARC method. We
      evaluated both the low-cost LNG IUD and all LARC methods. RESULTS: At the outset
      of preintroduction period, there were 29.2 [95% confidence interval (CI): 20.1
      38.4] monthly LNG IUD insertions. Immediately postintroduction, there was a
      significant level of increase of 14.4 LNG IUD insertions the first month (95% CI:
      2.0-26.8) followed by a significant trend increase each month of 2.4 additional
      LNG IUD insertions (95% CI: 0.32-4.47). Postintroduction, there was a significant
      level of remitted-payment decrease from all sources of -$240.43 per LNG IUD (95%
      CI: -311.02 to 168.87) followed by a significant monthly trend decrease of 
      $23.01 per LNG IUD (95% CI: -32.02 to -13.98). There were minimal changes in
      uptake and payment of other LARC methods following the introduction of the low
      cost LNG IUD. CONCLUSIONS: Following introduction of a low-cost LNG IUD at Title
      X clinics, LNG IUD initiation increased and average payment for the method
      decreased. IMPLICATIONS: Reducing the cost of LARC methods, both to clinics and
      to patients, is essential to expanding access. Additional efforts to develop and
      provide access to low-cost copper IUDs and subdermal implants as well as novel
      LARC methods should be continued.

PMID- 29574096
TI  - Measurement of indicator genes using global complementary DNA (cDNA)
      amplification, by polyadenylic acid reverse transcriptase polymerase chain
      reaction (poly A RT-PCR): A feasibility study using paired samples from tissue
      and ductal juice in patients undergoing pancreatoduodenectomy.
AB  - OBJECTIVES: The aim of this study is to compare gene expression profiles in RNA
      isolated from pancreatic ductal juice with the RNA expression profiles of the
      same genes from matched intra-operative tissue samples from pancreatic tumours.
      METHODS: Intra-operative sampling of pancreatic juice and collection of matched
      tissue samples was undertaken in patients undergoing pancreatoduodenectomy for
      clinically suspected pancreatic cancer and a precursor lesion, main-duct
      intraductal papillary mucinous neoplasm. RNA was isolated and Poly A PCR was used
      to globally amplify the RNA. Real-time polymerase chain reaction (RT-PCR) was
      used to measure expression levels of 17 genes selected from microarray studies.
      Spearman's rank correlation test was used to examine the relationship of gene
      expression between pancreatic juice and tissue. The study was approved by
      Regional Ethics Committee. RESULTS: Mesothelin (MSLN) showed significant
      correlation (p < 0.008) in expression levels between paired pancreatic juice and
      tissue samples in pancreas cancer. In intraductal papillary mucinous neoplasms
      (IPMN), Matrix Metalloproteinase 7 (MMP7), showed significant correlation (p <
      0.01) in the expression levels between paired pancreatic juice and tissue
      samples. CONCLUSION: This study confirms that RNA analysis of paired pancreatic
      juice and tissue samples and establishment of cDNA using poly A PCR is
      technically feasible. Application of the technique to non-invasively obtained
      pancreatic juice during endoscopic assessment of tumours and the use of gene
      arrays of cancer indicator genes are the next steps in development of this
      technique.

PMID- 29574097
TI  - Dynamic changes in hippocampal microglia contribute to depressive-like behavior
      induced by early social isolation.
AB  - Depression triggered by early-life stress has begun to attract wide attention due
      to its severe symptoms and poor treatment outcomes. However, the
      pathophysiological mechanism for this type of depression remains unclear.
      Recently, we and others reported that different types of chronic stress induce a
      significant loss of hippocampal microglia, which is mediated by an initial
      activation of these microglia. Since early-life stress also promotes microglial
      activation, we investigated the dynamic changes in hippocampal microglia in mice
      suffering from depression induced by early social isolation (ESI). Results showed
      that 8 days of ESI induced depressive-like behaviors in a tail suspension test,
      forced swim test, sucrose preference test, and open field test, and it also
      induced a loss and dystrophy of hippocampal microglia. We found that this ESI
      induced loss of hippocampal microglia was mediated by both microglial activation
      and apoptosis. This was demonstrated by the following results: (i) 1 day of ESI
      induced an obvious activation of hippocampal microglia followed by their
      apoptosis, and (ii) the blockade of the initial activation of hippocampal
      microglia by minocycline pretreatment suppressed the ESI-induced apoptosis and
      loss as well as ESI-induced depressive-like behavior. Lipopolysaccharide (LPS)
      and macrophage colony-stimulating factor (M-CSF), two activators of microglia,
      almost completely reversed ESI-induced depressive-like behavior by promoting
      microglial proliferation in the hippocampus. These results reveal an etiological
      role of hippocampal microglial loss in ESI-induced depression and demonstrate
      that the restoration of microglial homeostasis in the hippocampus may serve as a
      therapeutic strategy for depression induced by early-life stress.

PMID- 29574098
TI  - Inhibition of mitochondrial permeability transition pore opening contributes to
      cannabinoid type 1 receptor agonist ACEA-induced neuroprotection.
AB  - Cannabinoid type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA)
      induces neuroprotection against brain ischemia, and the mechanism, however, is
      still elusive. In this study, we used bilateral common carotid artery occlusion
      (BCCAO) in mice and oxygen-glucose deprivation (OGD) in primary cultured neurons
      to mimic brain ischemic injury, and hypothesized that cannabinoid CB1 receptor
      agonist ACEA protects ischemic neurons via inhibiting the opening of
      mitochondrial permeability transition pore (MPTP). In vivo, we found that BCCAO
      treatment reduced the neurological functions, increased the number of apoptotic
      neuronal cells and deteriorated the mitochondrial morphology in the ischemic
      brain tissue. And in vitro, we observed that OGD injury reduced cell viability,
      mitochondrial function and anti-oxidant SOD2 expression, increased lactate
      dehydrogenase (LDH), mitochondrial cytochrome C (Cyto C) and apoptosis-inducing
      factor (AIF) releases, elevated the cell apoptosis and mitochondrial superoxide
      level. And the CB1 receptor agonist ACEA significantly abolished the BCCAO and
      OGD-induced neuronal injury above. However, the MPTP opener atractyloside (Atr)
      markedly reversed the ACEA-induced neuroprotective effects, inhibited the
      mitochondrial Cyto C and AIF releases and relieved the mitochondrial swelling,
      but the MPTP inhibitor cyclosporin A (CsA) did not cause significant effects on
      the ACEA-induced neuroprotection above. These findings indicated that inhibition
      of MPTP opening may be involved in the cannabinoid CB1 receptor agonist ACEA
      induced neuroprotection.

PMID- 29574099
TI  - The Role of Laparoscopic Mini-Gastric Bypass in Management of Metabolic Syndrome.
AB  - OBJECTIVE: The study was performed to evaluate the technique of laproscopic
      minigastric bypass for metabolic syndrome patients. STUDY DESIGN: The patients
      were enrolled in a combined prospective study and had a retrospectively gathered
      outcome analysis. PATIENT AND METHODS: The study includes thirty patients; 24
      females and 6 males suffering from metabolic syndrome with a mean age of 33.15 +/
      10.17 years (range, 20-59), who fulfilled the criteria for bariatric surgery
      with BMI >35 with associated co-morbidities, all patients underwent laparoscopic
      mini-gastric bypass. RESULTS: BMI and WC were significantly reduced post
      operatively; also co-morbidities as DM, hypertension and dyslipidemia were
      resolved or controlled. The mean operative time was 90 +/- 12.6 min (range, 80
      120). No mortality was reported within 30 days of surgery. CONCLUSION:
      Laparoscopic mini gastric bypass is an effective procedure for the treatment of
      obesity, HTN, type 2 DM and dyslipidemia, technically feasible, safe operation
      with a low rate of major postoperative complications.

PMID- 29574100
TI  - Inhibitory role of the Bm8 protein in the propagation of Bombyx mori
      nucleopolyhedrovirus.
AB  - Lepidopteran nucleopolyhedroviruses have distinct viral tissue tropisms in host
      larvae. We previously identified the Bm8 gene of Bombyx mori nucleopolyhedrovirus
      (BmNPV), the product of which inhibits viral propagation in the middle silk gland
      (MSG). However, it is unknown whether this inhibitory function of the Bm8 protein
      is specific to MSGs. Here we generated a Bm8-disrupted recombinant BmNPV
      expressing green fluorescent protein (GFP) and examined viral propagation in B.
      mori cultured cells and larvae. We found that Bm8-disrupted BmNPV produced fewer
      budded viruses and more occlusion bodies (OBs) than the wild-type virus in both
      cultured cells and larvae. Microscopic observation of OB production and GFP
      expression revealed that Bm8 disruption accelerated the progression of viral
      infection in various larval tissues. Furthermore, quantitative reverse
      transcription-polymerase chain reaction experiments showed that the loss of Bm8
      enhanced viral gene expression in BmNPV-infected larval tissues. These results
      indicate that the Bm8 protein suppresses viral propagation to varying degrees in
      each larval tissue, which may establish BmNPV tissue tropisms in B. mori larvae.

PMID- 29574101
TI  - A novel virus (order Bunyavirales) from stressed redclaw crayfish (Cherax
      quadricarinatus) from farms in northern Australia.
AB  - Athtabvirus, a bunya-like virus and chequa iflavirus infect redclaw crayfish
      (Cherax quadricarinatus) and they may cause mortality reaching 20-40% after about
      three weeks following transportation stress. Lesions were seen in the muscles of
      broodstock and juveniles and nerve cords of craylings. Using NextGen sequencing,
      the whole transcriptomes of a farmed case crayfish and a tank-reared, unaffected
      crayfish were assembled producing over 500,000 contigs. The average depth of
      reads was 18 replicates with a range from 15 to 44. The near complete sequences
      of the large and middle genome segments of a bunya-like virus were detected along
      with chequa iflavirus. The internal bunya-like motifs; RNA-dependent RNA
      polymerase on the L segment, and glycoprotein n (Gn) on the M segment were easily
      identified. In the opposite, positive-sense direction on the M segment, another
      presumed glycoprotein (glycoprotein c) with a low-density lipoprotein receptor
      (cysteine-rich) motif was identified by position specific iterated (psi)-BLASTp.
      The athtabvirus was related to Whenzhou Shrimp Virus 2 (E = 0.0, 43% amino acid
      identity), an unassigned, -ve sense ssRNA virus, and to peribunyaviruses (E = 10
      50-20). In descending order of the number of RNA copies/0.2 mg of tissue, the
      organs most heavily infected were muscle (9.4 * 106), nerve cord (5.24 * 106),
      heart (4.07 * 106), gills (3.96 * 106), hepatopancreas (1.58 * 106) and antennal
      gland (6.6 * 105). Given the tissue tropism (muscle and nerves) of athtabvirus
      and the original lesions, this virus is implicated in being involved in the
      mortalities in crayfish after transportation.

PMID- 29574102
TI  - STATSLAB: An open-source EEG toolbox for computing single-subject effects using
      robust statistics.
AB  - Research on robust statistics during the past half century provides concrete
      evidence that classical hypothesis tests that rely on the sample mean and
      variance are problematic. Even seemingly minor departures from normality are now
      known to create major problems in terms of increased error rates and decreased
      power. Fortunately, numerous robust estimation techniques have been developed
      that circumvent the need for strict assumptions of normality and equal variances,
      leading to increased power and accuracy when testing hypotheses. Two robust
      methods that have been shown to have practical value across a wide range of
      applied situations are the trimmed mean and percentile bootstrap test. To
      facilitate the uptake of robust methods into the behavioural sciences, especially
      when dealing with trial-based data such as EEG, we introduce STATSLAB: An open
      source EEG toolbox for computing single-subject effects using robust statistics.
      With the STATSLAB toolbox users can apply the percentile bootstrap test, with
      trimmed means, to a variety of neural signals including voltages, global field
      amplitude, and spectral features for both scalp channels and independent
      components. The toolbox offers a range of analytical strategies and is packaged
      with a fully functional graphical user interface that includes documentation.

PMID- 29574103
TI  - Sevoflurane exaggerates cognitive decline in a rat model of chronic intermittent
      hypoxia by aggravating microglia-mediated neuroinflammation via downregulation of
      PPAR-gamma in the hippocampus.
AB  - Postoperative cognitive dysfunction is a common complication associated with
      anesthesia and surgery. Sevoflurane is a widely used volatile anesthetic in the
      clinical setting. Preclinical studies show that sevoflurane alone does not appear
      to cause cognitive dysfunction. Here, we examined whether sevoflurane induces
      cognitive decline under chronic intermittent hypoxia (CIH) conditions. Rats were
      exposed to CIH or control for 4 weeks. Two weeks after starting intermittent
      hypoxia, these animals underwent either 2.6% sevoflurane or vehicle exposure for
      4 h. Four weeks after CIH, Morris Water Maze task showed that both groups of CIH
      rats exhibited significantly longer latency to locate the hidden platform and had
      shorter dwell-time in the goal quadrant compared with respective controls.
      Notably, CIH + sevoflurane rats had much higher latency and less dwell-time than
      CIH + vehicle rats. Molecular studies revealed that pro-inflammatory cytokine
      expression and activated microglia in the hippocampus were increased in both
      groups of CIH rats, with greater increases in CIH + sevoflurane rats. No
      differences in above measured parameters were observed between two control
      groups. Sevoflurane reduced PPAR-gamma expression and activity in both control
      and CIH rats. Moreover, activated microglia was positively correlated with
      proinflammatory cytokine expression and negatively correlated with PPAR-gamma
      expression and activity in CIH groups. The results suggest that microglia
      mediated neuroinflammation in the hippocampus plays an important role in the
      pathogenesis of CIH-associated cognitive dysfunction, and that a moderate
      duration of sevoflurane exaggerates cognitive decline under CIH conditions by
      aggravating microglia-mediated neuroinflammation via downregulation of PPAR-gamma
      in the hippocampus.

PMID- 29574104
TI  - The Escherichia coli effluxome.
AB  - Multidrug transporters function in a coordinated mode to provide an essential
      first-line defense mechanism that prevents antibiotics from reaching lethal
      concentrations, until a number of stable efficient adaptations occur that allow
      survival. Single-component efflux transporters remove the toxic compounds from
      the cytoplasm to the periplasmic space where TolC-dependent transporters expel
      them from the cell. The close interaction between the two types of transporters
      ensures handling of a wide range of xenobiotics and prevents rapid leak of the
      hydrophobic substrates back into the cell. In this review, we discuss the concept
      of the bacterial effluxome of the Gram-negative Escherichia coli that is the
      entire set of transporters expressed at a given time, under defined conditions.
      The process of identification of its members and the elucidation of the nature of
      the interactions throw a novel light on the roles of transporters in bacterial
      physiology and drug resistance development. We anticipate that the concept of an
      effluxome where each member contributes to the removal of noxious chemicals from
      the cell should contribute to improving the present strategy of searching for
      transport inhibitors as adjuvants of existing antibiotics and provide novel
      targets for this urgent undertaking.

PMID- 29574105
TI  - Increased risk of diabetes development in individuals with weight cycling over 4
      years: The Kangbuk Samsung Health study.
AB  - AIMS: Weight cycling is defined as cyclical loss and gain of weight and recent
      studies suggest deleterious effects of weight cycling on cardiometabolic health.
      We aimed to analyze the risk for diabetes development in association with weight
      cycling over 4 years of follow-up. METHODS: A retrospective study performed in
      4,818 non-diabetic participants (mean age 43 years, 78.3% men) in a health
      screening program in whom serial health examinations were performed in 5
      consecutive years from 2010 to 2014. Average successive variability of weight
      (ASVW) was defined by the amount of body weight change in absolute value between
      the successive years over 5 years summed and divided by four. The subjects were
      divided into two groups according to body mass index (BMI), normal weight (<23
      kg/m2) and overweight (>=23 kg/m2). RESULTS: Over 4 years, 3.2% developed
      diabetes. When the subjects were divided into 3 groups according to tertile
      groups of ASVW, those in the highest tertile showed significantly increased risk
      for diabetes development compared to those with the lowest tertile {odds ratio
      (OR) 1.860; 95% CI 1.130-3.063}. When similar analyses were performed according
      to the 4 groups divided by baseline body weight and ASVW over four years, those
      who were more than overweight at baseline with high ASVW showed significantly
      increased risk of diabetes development compared to those had normal weight and
      low ASVW (OR 2.266; 95% 1.123-4.572). When the subjects were divided into six
      group according to weight change and ASVW, those with increased weight over 4
      years and high ASVW showed the highest risk for diabetes development among the
      groups compared to those with stable weight and low ASVW over four years (OR
      3.660; 95% CI 1.402-9.553). CONCLUSIONS: Those with high ASVW showed
      significantly increased risk for diabetes development over four years compared
      with those who had low ASVW. Weight cycling was significantly associated with
      increased risk for diabetes.

PMID- 29574106
TI  - Self-reported color-race and genomic ancestry in an admixed population: A
      contribution of a nationwide survey in patients with type 1 diabetes in Brazil.
AB  - AIMS: The development of type 1 diabetes (T1D) and its chronic complications may
      have a genetic background. The primary objective of our study was to characterize
      the relationship between self-reported color-race and genomic ancestry (GA) in
      patients with T1D. As secondary objective, we aimed to characterize GA of
      patients with T1D from different urban geographical regions of Brazil, compared
      to healthy Brazilian controls from the same regions. METHODS: This was a cross
      sectional, nationwide survey conducted in 14 public clinics from 10 Brazilian
      cities. Global and individual GA were inferred using a panel of 46 ancestry
      informative markers (AIMs) in 1698 T1D patients. Ancestry percentage was compared
      with published data of Brazilian healthy controls (n = 936) for the same AIMs.
      RESULTS: A higher median individual European ancestry was observed in T1D
      patients in comparison to controls 67.8 [31.2] vs. 56.3 [25.7]%, respectively
      (median [IQR]; p < 0.001). As for self-reported color-race in T1D group, 923
      (54.3%) participants reported to be White, 610 (35.9%) Brown, 132 (7.8%) Black,
      18 (1.1%) Asian and 15 (0.9%) Indigenous. European GA prevailed in those who self
      reported as White (74.6%) and Brown (61.1%) and constituted 39.1% in Black self
      reported patients. CONCLUSIONS: Our study showed that T1D patients presented a
      higher percentage of European GA than the healthy population. Additionally,
      European GA was found in a considerable percentage of T1D patients who self
      reported as non-White. Further studies are necessary to establish the influence
      of GA in the development of T1D as well its related chronic complications in
      admixed populations.

PMID- 29574107
TI  - Evaluation of the impact of a diabetes education eLearning program for school
      personnel on diabetes knowledge, knowledge retention and confidence in caring for
      students with diabetes.
AB  - AIMS: To study the impact of a novel comprehensive eLearning approach in
      delivering diabetes related education program that includes knowledge and sets of
      practices to the school personnel in Kuwait to enable them to provide a
      supportive environment for students with diabetes. METHODS: The program was
      designed with three components namely; knowledge, skills and recommendations. The
      diabetes knowledge was delivered through an interactive eLearning program, the
      effectiveness of which was assessed using diabetes knowledge questionnaires which
      were deployed pre- and post-course delivery. Additionally, the participants'
      knowledge retention and confidence in caring for a student with diabetes were
      evaluated at 6 or 12 months post-intervention. RESULTS: A total of 124 public
      schools' personnel participated in the program. Post e-Learning delivery,
      diabetes knowledge increased significantly from baseline (p < 0.0001) and
      knowledge was retained over 6 and 12 months. Average of overall confidence scores
      in caring for students with diabetes was 61.86% in all items of care.
      CONCLUSIONS: Offering eLearning diabetes education for school personnel increases
      their knowledge which can be retained for up to 12 months and imparts confidence
      in caring for students with diabetes. This novel approach of delivering diabetes
      education will help school personnel in managing students with diabetes.

PMID- 29574108
TI  - Diabetes is associated with increased prevalence of latent tuberculosis
      infection: Findings from the National Health and Nutrition Examination Survey,
      2011-2012.
AB  - AIMS: We aim to determine the association between prediabetes and diabetes with
      latent TB using National Health and Nutrition Examination Survey data. METHODS:
      We performed a cross-sectional analysis of 2011-2012 National Health and
      Nutrition Examination Survey data. Participants >=20 years were eligible.
      Diabetes was defined by glycated hemoglobin (HbA1c) as no diabetes (<=5.6% [38
      mmol/mol]), prediabetes (5.7-6.4% [39-46 mmol/mol]), and diabetes (>=6.5% [48
      mmol/mol]) combined with self-reported diabetes. Latent TB infection was defined
      by the QuantiFERON(r)-TB Gold In Tube (QFT-GIT) test. Adjusted odds ratios (aOR)
      of latent TB infection by diabetes status were calculated using logistic
      regression and accounted for the stratified probability sample. RESULTS: Diabetes
      and QFT-GIT measurements were available for 4958 (89.2%) included participants.
      Prevalence of diabetes was 11.4% (95%CI 9.8-13.0%) and 22.1% (95%CI 20.5-23.8%)
      had prediabetes. Prevalence of latent TB infection was 5.9% (95%CI 4.9-7.0%).
      After adjusting for age, sex, smoking status, history of active TB, and foreign
      born status, the odds of latent TB infection were greater among adults with
      diabetes (aOR 1.90, 95%CI 1.15-3.14) compared to those without diabetes. The odds
      of latent TB in adults with prediabetes (aOR 1.15, 95%CI 0.90-1.47) was similar
      to those without diabetes. CONCLUSIONS: Diabetes is associated with latent TB
      infection among adults in the United States, even after adjusting for confounding
      factors. Given diabetes increases the risk of active TB, patients with co
      prevalent diabetes and latent TB may be targeted for latent TB treatment.

PMID- 29574109
TI  - Comparative Survival following Initial Cytoreductive Nephrectomy versus Initial
      Targeted Therapy for Metastatic Renal Cell Carcinoma.
AB  - PURPOSE: The optimal sequence of cytoreductive nephrectomy and targeted therapy
      of metastatic renal cell carcinoma is unclear. We compared overall survival
      between patients with metastatic renal cell carcinoma treated with initial
      cytoreductive nephrectomy with or without subsequent targeted therapy vs initial
      targeted therapy with or without subsequent cytoreductive nephrectomy. MATERIALS
      AND METHODS: We evaluated the records of cases in the National Cancer Database
      diagnosed with metastatic renal cell carcinoma between 2006 and 2013 who were
      treated with cytoreductive nephrectomy and/or targeted therapy. Receipt of
      targeted therapy after initial cytoreductive nephrectomy and cytoreductive
      nephrectomy after initial targeted therapy were evaluated on competing risks
      analyses. To account for treatment selection bias, inverse probability of
      treatment weighting was performed based on the propensity to receive initial
      cytoreductive nephrectomy or initial targeted therapy. Overall survival was
      compared between the groups by Kaplan-Meier analysis and Cox proportional hazards
      regression. RESULTS: Of the 15,068 patients included in study 6,731 underwent
      initial cytoreductive nephrectomy and 8,337 received initial targeted therapy.
      Six months after initial cytoreductive nephrectomy 48.0% of patients received
      targeted therapy, of whom 15.3% died after initial cytoreductive nephrectomy
      prior to targeted therapy. Six months after initial targeted therapy 4.7% of
      patients underwent cytoreductive nephrectomy, of whom 44.9% died after initial
      targeted therapy prior to cytoreductive nephrectomy. Initial cytoreductive
      nephrectomy (OR 2.02, 95% CI 1.69-2.43, p <0.001) and cytoreductive nephrectomy
      after initial targeted therapy (HR 2.6, 95% CI 1.69-4.01, p <0.001) were more
      likely to be performed at academic vs community institutions. On inverse
      probability of treatment weighting analysis initial cytoreductive nephrectomy was
      associated with improved overall survival compared to initial targeted therapy
      (median 16.5 vs 9.2 months, HR 0.61, 95% CI 0.59-0.64, p <0.001). CONCLUSIONS:
      Given the greater likelihood of receiving multimodal therapy and the associated
      overall survival benefit, these data support cytoreductive nephrectomy as the
      initial approach to metastatic renal cell carcinoma in appropriate surgical
      candidates. Continued efforts are warranted to establish the optimal multimodal
      approach in these patients.

PMID- 29574110
TI  - Targeted Antimicrobial Prophylaxis Does Not Always Prevent Sepsis after
      Transrectal Prostate Biopsy.
AB  - PURPOSE: We compared the effectiveness of targeted prophylaxis to augmented
      empirical prophylaxis and single agent empirical prophylaxis to prevent sepsis
      after transrectal prostate biopsy. MATERIALS AND METHODS: We retrospectively
      reviewed the records of transrectal prostate biopsies performed during 3 years at
      13 Southern California Kaiser Permanente(r) departments of urology. Targeted
      prophylaxis was guided by rectal culture bacterial susceptibility for use of a
      single prophylactic antibiotic while for empirical prophylaxis 1 antibiotic
      (single agent empirical prophylaxis) or multiple antibiotics (augmented empirical
      prophylaxis) were given according to the usual practice of the urologist. Sepsis
      was the primary outcome analyzed. RESULTS: We reviewed 15,236 transrectal
      prostate biopsy cases. Targeted prophylaxis, single agent empirical prophylaxis
      and augmented empirical prophylaxis were administered in 26%, 58% and 16% of
      cases, respectively. The overall incidence of post-biopsy sepsis was 0.64%. On
      multivariable analysis there was no significant difference in the rate of post
      biopsy sepsis after targeted prophylaxis compared to empirical prophylaxis
      (single agent and augmented empirical prophylaxis together) (OR 0.86, 95% CI 0.53
      1.41, p = 0.561). However, on subanalysis augmented empirical prophylaxis showed
      a significantly lower incidence of sepsis than single agent empirical or targeted
      prophylaxis (OR 0.35, 95% CI 0.16-0.76, p = 0.008). Based on blood and urine
      cultures 38% of the patients with sepsis after transrectal prostate biopsy had
      been given the correct prophylactic antibiotic prior to biopsy. On multivariable
      analysis Asian/Pacific Islander or Hispanic/Latino ethnicity was associated with
      a higher incidence of harboring fluoroquinolone resistant bacteria on rectal swab
      cultures. CONCLUSIONS: This large retrospective study showed that augmented
      empirical prophylaxis was statistically superior to single agent empirical and
      targeted prophylaxis. Sepsis developed in a significant number of patients
      despite being given a prophylactic antibiotic to which the sepsis causing
      bacteria were sensitive.

PMID- 29574111
TI  - Isolated lateral cervical swelling in a adolescent.

PMID- 29574112
TI  - Ameloblastic fibrodentinosarcoma and ameloblastic fibro-odontosarcoma: A
      systematic review.
AB  - The purpose of the present review was to integrate the available data published
      on ameloblastic fibrodentinosarcoma (AFDS) and ameloblastic fibro-odontosarcoma
      (AFOS) into a comprehensive analysis of their clinical/radiologic features. An
      electronic search was undertaken in July/2017. Eligibility criteria included
      publications having enough clinical/radiological/histological information to
      confirm the diagnosis. Seventeen publications (8 AFDS, 9 AFOS) were included. The
      patients with the two different lesions had a similar mean age. The lesions were
      both more prevalent in mandibles than in maxillae, all showed bone expansion and
      similar rates of cortical bone perforation, tooth displacement, and locular
      appearance at radiological exams. Mean follow-up time was higher for AFDS, and
      the mean size of the lesions were larger for AFDS, although without a
      statistically significant difference. None of AFDS recurred, while 2 AFOS
      recurred. As only few cases of AFDS and AFOS have been reported, additional
      reports are necessary to add evidence to the study of clinical and radiologic
      features of these lesions.

PMID- 29574113
TI  - Transgenerational analysis of H3K4me3 and H3K27me3 by ChIP-Seq links epigenetic
      inheritance to metabolism.

PMID- 29574114
TI  - Hepatocytes in a normal adult liver are derived solely from the embryonic
      hepatocytes.

PMID- 29574115
TI  - Fifty years of stress and more to come: A tribute to Bruce S. McEwen.

PMID- 29574116
TI  - Predicting the oxygen cost of walking in hemiparetic stroke patients.
AB  - OBJECTIVE: To verify the relation between spontaneous walking speed (Sfree) and
      oxygen cost of walking at Sfree (Cwfree) in post-stroke hemiparetic patients and
      to test the validity of a prediction model to estimate Cwfree based on Sfree.
      DESIGN: We included 26 participants (mean age 65.1 years [SD 15.7]) with mild to
      moderate disability after stroke who walked at Sfree using mobility aids if
      necessary for 6min. The Cwfree was measured at a stabilized metabolic rate by
      indirect calorimetry with the Metamax 3B spiroergometry device. The relation
      between Sfree and Cwfree was analyzed by the correlation coefficient (r) and
      coefficient of determination (R2). The Cwfree prediction model was developed from
      a regression equation, then tested on a second population of 29 patients (mean
      age 62.1 years [SD 13.4]) with the same inclusion and exclusion criteria.
      RESULTS: For the 26 participants, the Sfree and Cwfree were highly correlated (r=
      0.94 and R2=0.97), which allowed for formulating a regression equation and
      developing the Cwfree prediction model based on Sfree. The prediction model tests
      yielded accurate results (mean bias -0.02mL.kg-1.m-1; 95% limits of agreement 
      0.31 to 0.26mL.kg-1.m-1). The relation between Cwfree estimated by the model and
      measured by Metamax was high (R2=0.98). CONCLUSION: Cwfree was strongly
      correlated with Sfree, which allowed for the development of a valid Cwfree
      prediction model. A practitioner could estimate the energy expenditure of walking
      for a patient without using an indirect calorimeter.

PMID- 29574117
TI  - GAPDH as a model non-canonical AU-rich RNA binding protein.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a key role in glycolysis
      but is also known for its involvement in a myriad of extra-glycolytic functions.
      While GAPDH is not the only enzyme with established moonlighting roles, it shows
      great diversity in terms of its functions, cellular localizations, protein
      partners, and post-translational modifications. This review focuses on GAPDH's
      role as a non-canonical RNA binding protein to regulate the stability and
      translation of cellular mRNAs. Despite the clear involvement of GAPDH in gene
      expression regulation, how and where GAPDH binds to its RNA targets is still
      unknown. In addition, the mechanism by which GAPDH switches among its various
      cellular functions is also unknown. This review will summarize our current
      understanding of GAPDH-mediated regulation of RNA function.

PMID- 29574118
TI  - Selection of specific aptamer against enrofloxacin and fabrication of graphene
      oxide based label-free fluorescent assay.
AB  - Specific ssDNA aptamers for the antibiotic enrofloxacin (ENR) were isolated from
      an enriched nucleotide library by SELEX (Systematic Evolution of Ligands by
      EXponential enrichment) method with high binding affinity. After seven rounds,
      five aptamers were selected and identified. Apt58 with highest affinity and
      sensitivity (Kd = 14.19 nM) was employed to develop a label-free fluorescent
      biosensing approach based on aptamer, graphene oxide (GO) and native fluorescence
      of ENR for determination of ENR residue in raw milk samples. Under optimized
      experimental conditions, the linear range was from 5 nM to 250 nM and LOD was
      calculated to be 3.7 nM, and the recovery rate was between 94.1% and 108.5%. The
      integration of aptamer and GO in this bioassay provides a promising way for
      rapid, sensitive and cost-effective detection of ENR in real samples like raw
      milk.

PMID- 29574119
TI  - Scrubbing technique for needleless connectors to minimize contamination risk.
AB  - This study aimed to investigate the appropriate scrubbing technique for
      needleless connectors to minimize contamination risk. To demonstrate a highly
      effective scrubbing technique to physically eliminate bacteria, needleless
      connectors were contaminated with Geobacillus stearothermophilus spores and then
      scrubbed. The study showed that the highest bacterial elimination rate was
      achieved by scrubbing an access port in a straight line with an alcohol cotton
      swab, applying a force that was almost equal to an arterial compression
      haemostasis to the access port, and repeating this procedure once using a new
      alcohol cotton swab.

PMID- 29574120
TI  - Response to Kaier et al. regarding 'Estimating the additional costs of surgical
      site infections'.

PMID- 29574121
TI  - Sacral Neuromodulation and Twiddler's Syndrome.
AB  - Twiddler's syndrome is the deliberate, inadvertent, or subconscious manipulation
      of an implantable generator within its subcutaneous pocket that can lead to
      malposition and fracture of the associated lead. The syndrome is well recognized
      in patients with pacemakers, implantable cardioverter defibrillators, deep brain
      stimulators, and more recently in intrathecal drug delivery devices. Here we
      present an instance of Twiddler's syndrome after sacral neuromodulation.

PMID- 29574122
TI  - Autologous Rectus Fascia Graft Interposition Repair of Urethrocutaneous Fistulae
      in Female-to-Male Metoidioplasty Patients.
AB  - OBJECTIVE: To describe our technique and outcomes using an autologous rectus
      fascia interposition graft for repair of recurrent urethrocutaneous fistulae
      (UCF) following metoidioplasty. MATERIALS AND METHODS: A circumferential incision
      is made to the skin surrounding the UCF and carried to the level of the
      underlying subcutaneous tissues. The inner fistula skin edges are closed with a
      running 5-0 monofilament absorbable suture to obliterate the urethral side. The
      length of the urethral wound is measured and an appropriate sized rectus fascia
      graft harvested from a small transverse lower abdominal incision that is also
      used for concomitant percutaneous suprapubic tube placement. Prior to outer skin
      closure with a running 5-0 monofilament absorbable suture, the fascial graft is
      spread-fixed between the urethra and skin to avoid overlapping suture lines. A 10
      French urethral catheter is removed after 10 days and the suprapubic catheter
      removed after 2-3 weeks. RESULTS: Three patients have undergone repair of
      recurrent UCF with this technique since February 2017. All patients had undergone
      metoidioplasty with a mean time to fistula occurrence of 3.2 months. Mean number
      of prior UCF repairs was 3.0. With a median follow-up since repair of 7.0 months
      (range 4-8), no patient has reported UCF recurrence. CONCLUSION: UCF following
      metoidioplasty is a difficult surgical complication. Fistula closure with
      interposition of autologous rectus fascia allows for separation of suture lines
      and encourages healing without extensive reconstruction.

PMID- 29574123
TI  - Decisional Quality in Patients With Small Renal Masses.
AB  - OBJECTIVE: To measure decisional quality in patients being counseled on treatment
      for small renal masses and identify potential areas of improvement. MATERIALS AND
      METHODS: A total of 73 patients diagnosed with small renal masses at the
      University of California, Los Angeles Health completed an instrument measuring
      decisional conflict, patient satisfaction with care, disease-specific knowledge,
      and patient impression that shared decision-making occurred in the visit after
      counseling by a specialist. Participant characteristics were compared between
      those with high and low decisional conflict using chi-square or Student t test
      (or Wilcoxon rank-sum test). RESULTS: Participants were mostly older (mean age
      63.5), white (84%), in a relationship (61%), and unemployed or retired (63%).
      Mean knowledge score was 59% correct. The mean (standard deviation) decisional
      conflict score was 16.4 (18.4) indicating low levels of decisional conflict but
      with a wide range of scores. Comparing participants with high decisional conflict
      with those with low decisional conflict, there were significant differences in
      knowledge scores (Wilcoxon P = .0069), patient satisfaction with care (P =
      .0011), and perceived shared decision-making (P <.0001). CONCLUSION: Patients
      with small renal masses generally have low levels of decisional conflict and can
      identify a preferred treatment after a physician visit. However, both groups lack
      overall knowledge about their disease even after counseling, and thus may be
      heavily influenced by paternalistic care. Those patients with decisional
      conflicts are less likely to perceive their care as satisfactory and are less
      likely to be involved in decision-making.

PMID- 29574124
TI  - Providing Level-of-Match Information to Perfectly Matched Unrelated Stem Cell
      Donors: Evaluating Acceptability and Potential Changes in Donor Availability.
AB  - Patients with blood-related diseases often cannot identify a matched related
      donor and must seek donors in unrelated donor registries. These registries face
      the challenge of ensuring that potential donors are available when contacted.
      Donor attrition is especially problematic when there is only a single perfectly
      matched potential donor. One way to improve donor availability might be to
      present perfectly matched donors (high-priority donors [HPDs]) with more precise
      information about their match status. This project evaluated the impact of
      providing such information to HPDs at the National Marrow Donor Program (NMDP)/Be
      The Match. Objectives were to determine the acceptability of the new messaging to
      both HPDs and the donor contact representatives (DCRs) who delivered the message,
      consistency of message delivery, and whether the new messaging was associated
      with improved donor availability. Mixed methods were used to collect telephone
      interview data from HPDs, matched samples of non-HPDs, and DCRs. Donor
      availability data came from NMDP records. Key findings were as follows: (1) the
      HPD message was acceptable to potential donors and did not seem to produce undue
      pressure, (2) the message was acceptable to DCRs who became more comfortable and
      consistent in delivering the message over time, but (3) the new messaging did not
      significantly increase availability. Despite the lack of evidence for increased
      availability, there may be ethical benefits and little harm to providing well
      matched donors with more information about their degree of matching. Research
      should examine stronger match status messages and delivery of new messaging to
      additional highly-matched donor groups.

PMID- 29574125
TI  - Higher incidence of metachronous advanced neoplasia in patients with synchronous
      advanced neoplasia and left-sided colorectal resection for colorectal cancer.
AB  - BACKGROUND AND AIMS: There is an increased risk of developing metachronous
      colorectal cancer (CRC) in the remnant colorectum after surgical resection of
      CRC. We evaluated the incidence of metachronous advanced neoplasia (AN) after
      surgery for CRC according to resection type and synchronous AN. METHODS: This
      cohort study included patients who underwent surgical resection for initial CRC
      at a tertiary cancer center in Japan between September 2002 and December 2012.
      The cumulative probability of metachronous AN was calculated using the Kaplan
      Meier method and was evaluated by the log-rank test. RESULTS: Metachronous AN was
      detected in 145 of 1731 included patients, and the 5-year cumulative probability
      of metachronous AN was 13.1%. There was no significant difference in the
      incidence of metachronous AN in the right-sided colorectal resection versus left
      sided colorectal resection (LCR) groups (log-rank test P = .151), whereas the
      incidence of metachronous AN was significantly higher in patients with
      synchronous AN (log-rank test P < .001). In subgroup analysis of patients
      according to resection type and synchronous AN, the LCR group with synchronous AN
      showed a significantly higher incidence of metachronous AN than the other groups
      (log-rank test P < .001). CONCLUSIONS: We found that synchronous AN, but not
      resection type, was independently associated with the incidence of metachronous
      AN in patients who underwent surgical resection of CRC. In addition, subjects
      with synchronous AN after LCR had a potentially increased risk for metachronous
      AN. Thus, it may be useful to perform risk stratification according to
      synchronous AN and resection type.

PMID- 29574126
TI  - Stent placement by EUS or ERCP for primary biliary decompression in pancreatic
      cancer: a randomized trial (with videos).
AB  - BACKGROUND AND AIMS: Studies on EUS-guided transmural biliary drainage (EUS-BD)
      have evaluated its efficacy as a rescue technique after failed ERCP. We performed
      a single-center, single-blind, randomized trial to compare EUS-BD and ERCP as
      primary treatment for distal biliary obstruction in pancreatic cancer. METHODS:
      Patients underwent EUS-BD (n = 33) or ERCP (n = 34). The primary endpoint was the
      rate of adverse events. Secondary endpoints were technical success, treatment
      success (defined as decline in serum bilirubin by 50% at a 2-week follow-up),
      reinterventions, and intraoperative technical outcome, when applicable. Follow-up
      was until death or a minimum of 6 months. RESULTS: The rates of adverse events
      were 21.2% (6.1% moderate severity; others mild severity) in the EUS-BD group and
      14.7% (5.9% moderate severity; others mild severity) in the ERCP group (risk
      ratio, .69; 95% confidence interval, .24-1.97; P = .49). There were no procedure
      related deaths. There was no significant difference in the rates of technical
      success (90.9% vs 94.1%, P = .67), treatment success (97% vs 91.2%, P = .61), or
      reinterventions (3.0% vs 2.9%, P = .99) between EUS-BD and ERCP cohorts,
      respectively. The endoscopic interventions did not impede subsequent
      pancreaticoduodenectomy that was performed in 5 of 33 patients (15.2%) in the EUS
      BD and 5 of 34 patients (14.7%) in the ERCP group (P = .99). CONCLUSIONS: Given
      the similar rates of adverse events and treatment outcomes in this randomized
      trial, EUS-BD is a practical alternative to ERCP for primary biliary
      decompression in pancreatic cancer. (Clinical trial registration number:
      NCT03054987.).

PMID- 29574127
TI  - Unusual Clinical Manifestation of Laryngeal Edema in a Case of DRESS Syndrome.

PMID- 29574128
TI  - Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for
      anticancer applications.
AB  - Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell
      proliferation, survival, migration and differentiation. Area of intense research
      is searching for effective anticancer therapies targeting these receptors and, to
      date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors
      have entered the clinic. However, some of these drugs show limited efficacy and
      give rise to acquired resistance. Emerging highly selective compounds for
      anticancer therapy are oligonucleotide aptamers that interact with their targets
      by recognizing a specific three-dimensional structure. Because of their nucleic
      acid nature, the rational design of advanced strategies to manipulate aptamers
      for both diagnostic and therapeutic applications is greatly simplified over
      antibodies. In this manuscript, we will provide a comprehensive overview of
      oligonucleotide aptamers as next generation strategies to efficiently target RTKs
      in human cancers.

PMID- 29574129
TI  - Activity dependent internalization of the glutamate transporter GLT-1 requires
      calcium entry through the NCX sodium/calcium exchanger.
AB  - GLT-1 is the main glutamate transporter in the brain and its trafficking controls
      its availability at the cell surface, thereby shaping glutamatergic
      neurotransmission under physiological and pathological conditions. Extracellular
      glutamate is known to trigger ubiquitin-dependent GLT-1 internalization from the
      surface of the cell to the intracellular compartment, yet here we show that
      internalization also requires the participation of calcium ions. Consistent with
      previous studies, the addition of glutamate (1 mM) to mixed primary cultures
      (containing neurons and astrocytes) promotes GLT-1 internalization, an effect
      that was suppressed in the absence of extracellular Ca2+. The pathways of Ca2+
      mobilization by astrocytes were analyzed in these mixed cultures using the
      genetically encoded calcium sensor GCaMP6f. A complex pattern of calcium entry
      was activated by glutamate, with a dramatic and rapid rise in the intracellular
      Ca2+ concentration partially driven by glutamate transporters, especially in the
      initial stages after exposure to glutamate. The Na+/Ca2+ exchanger (NCX) plays a
      dominant role in this Ca2+ mobilization and its blockade suppresses the glutamate
      induced internalization of GLT-1, both in astrocytes and in a more
      straightforward experimental system like HEK293 cells transiently transfected
      with GLT-1. This regulatory mechanism might be relevant to control the amount of
      GLT-1 transporter at the cell surface in conditions like ischemia or traumatic
      brain injury, where extracellular concentrations of glutamate are persistently
      elevated and they promote rapid Ca2+ mobilization.

PMID- 29574130
TI  - Gut microbiota analysis of juvenile genetically improved farmed tilapia
      (Oreochromis niloticus) by dietary supplementation of different resveratrol
      concentrations.
AB  - The genetically improved farmed tilapia (GIFT, Oreochromis niloticus) is cultured
      widely for production of freshwater fish in China, while streptococcosis, likely
      related to pathogenic infections, occurs frequently in juvenile, mother, and
      operated GIFT. The gut microbiota plays an important role in nutrient
      digestibility in animals, and resveratrol (RES) has been used in feed for
      different freshwater fish species. Therefore, understanding changes in the
      tilapia gut microbiota across different concentrations of dietary RES
      supplementation is extremely important. The gut microbiota population in tilapia
      at 45 d after supplementation with different concentrations (0, 0.025, 0.05, 0.1
      g/kg) of dietary RES was assessed by 16S rDNA gene sequencing. A total of 5445
      operational taxonomic units were identified from all samples, and 14 phyla and 81
      families were identified from all fecal samples. The bacteria of the phylum
      Firmicutes were significantly enriched in the 0.025 g/kg RES group when compared
      with the controls. Proteobacteria, Firmicutes and Cyanobacteria were the most
      dominant three phyla in all samples. With the increasing concentrations, the
      proportion of beneficial microbial taxa (Acetobacteraceae and
      Methylobacteriaceae) increased, whereas the proportion of harmful microbial taxa
      decreased, eg. Streptococcaceae except for 0.1 g/kg RES groups. RES did not
      affect the richness and diversity in tilapia gut microbiota. These findings
      provide information on the diversity and differences in GIFT gut microbiota
      database, and may contribute to developing strategies for management of diseases
      and long-term sustainability of O. niloticus culture.

PMID- 29574131
TI  - A tumor-activatable particle with antimetastatic potential in breast cancer via
      inhibiting the autophagy-dependent disassembly of focal adhesion.
AB  - In attempts to explore the role of autophagy in breast cancer metastasis, we here
      report a tumor-activatable particle (named as "D/PSP@CQ/CaP") with the ability of
      efficient autophagy inhibition. D/PSP@CQ/CaP was prepared by coprecipitating
      chloroquine phosphate (CQ) with calcium chloride, in the form of chloroquine
      calcium phosphate coprecipitate (CQ/CaP), onto the surface of a deep-tumor
      penetrating doxorubicine (DOX)-loading core particle (named as "D/PSP"). CQ/CaP
      could partly disintegrate and release CQ within tumor microenvironment and
      totally be dissolved within lysosomes. Paxillin is a key component of focal
      adhesion which functions to anchor tumors cells within the primary tumor for
      limiting cancer cells' detachment from the primary tumor. We tested that
      autophagy inhibition caused by CQ released from CQ/CaP could reduce the
      degradation of paxillin by 2.9 folds in vitro and 2.5 folds in vivo (vs.
      Control), respectively. Thus metastasis could be influenced by exploiting
      autophagy-dependent paxillin degradation. Data analysis together proved that
      D/PSP@CQ/CaP decreased the cancer metastatic extent by 7.5 folds (vs. Control) on
      mice model via inhibiting the autophagy-dependent disassembly of focal adhesion.
      At the same time, the growth rate of tumors treated by D/PSP@CQ/CaP was inhibited
      by 9.1 folds (vs. Control), which could be attributed to its effective tumor drug
      delivery.

PMID- 29574132
TI  - Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection
      against cisplatin-induced nephrotoxicity.
AB  - Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the
      use of CP was hampered by its serious side effects especially nephrotoxicity.
      This study aims to investigate the effect of resveratrol (RES) on CP-induced
      nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs).
      Male white albino rats were divided to four group's six rats each. The first
      group received (1%) tween 80 in normal saline and served as control. The second
      group received RES (30 mg kg-1) per day for 14 consecutive day's i.p. The third
      and fourth groups were given a single i.p. injection of CP (6 mg kg-1) with or
      without pre-treatment of RES (30 mg kg-1per day for 14 consecutive days),
      respectively. Following administration of CP, plasma, urine and kidney platinum
      concentration were monitored to study PKs of CP. Five days after the CP
      injection, rats were killed; blood samples were collected; kidneys were
      dissected; and biochemical, immunohistochemical, and histological examinations
      were performed. Our results revealed that CP treatment significantly deteriorated
      kidney functions with subsequent alteration in redox balance of the kidney. On
      the other hand, RES successfully ameliorated CP-induced kidney injury and
      recovered normal kidney tissue redox status. Importantly, while RES pre-treatment
      did not significantly alter the plasma CP level, it dramatically decreased the
      urine concentration of CP and lowered its accumulation into the kidneys.
      Moreover, it increased CP plasma half-life (t1/2) with subsequent decrease in its
      elimination rate constant, indicating an important role of PKs modulation in RES
      protection against CP-induced renal damage. Taken together, RES may protect the
      kidney tissue from the deleterious effects of CP through constringe of CP renal
      accumulation and enhancement of CP-induced oxidative stress.

PMID- 29574133
TI  - Kaempferol protects against propacetamol-induced acute liver injury through
      CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress,
      inflammation and apoptosis in mice.
AB  - Acetaminophen (APAP) overdose can induce acute liver injury (ALI) with
      significant morbidity and mortality. Propacetamol is an APAP prodrug, which is
      clinically bioequivalent to APAP. Kaempferol, a dietary flavonoid, has
      antioxidant, anti-inflammatory, and anti-apoptotic effects. In this study, we
      investigated the protective effect of kaempferol on propacetamol-induced ALI and
      its underlying mechanism in mice. Kaempferol pretreatment (125 mg/kg) before
      propacetamol injection significantly decreased propacetamol-induced serum ALT and
      AST activities, and DNA fragmentation. Kaempferol administration also reduced
      propacetamol-induced oxidative stress by inhibiting thiobarbituric acid reactive
      substances (TBARS) and 3-nitrotyrosine (3-NT) formation partly through
      downregulation of cytochrome P450 2E1 (CYP2E1) expression, upregulation of UDP
      glucuronosyltransferase family 1 member A1 (UGT1A1) expression, restoration of
      the activities of antioxidant enzymes including SOD, GPx and catalase toward
      normal, recovery of propacetamol-suppressed Nrf2 and GCLC expressions, and
      maintenance of normal glutathione level. Furthermore, kaempferol markedly
      attenuated APAP-induced serum TNF-alpha and IL-6 productions, downregulated APAP
      induced phosphorylations of JNK and ERK, and decreased early hepatic apoptosis
      via decreasing Bax/Bcl-2 ratio and caspase 3 activation. Furthermore,
      administration of N-acetylcysteine (NAC) and kaempferol significantly rescued
      more mice than a low dose of NAC only did when a lethal dose of propacetamol
      injected and therapized at a delayed time point. These data suggested that
      kaempferol protects the liver against propacetamol-induced injury through anti
      oxidative, anti-inflammatory and anti-apoptotic activities.

PMID- 29574134
TI  - Assessment of N-acetylcysteine as a therapy for phosgene-induced acute lung
      injury.
AB  - The toxic industrial chemical (TIC1) phosgene remains an important chemical
      intermediate in many industrial processes. Inhalation of phosgene can cause an
      acute lung injury (ALI) which, in severe cases may result in death. There are
      currently no effective pharmacological therapies or evidence-based treatment
      guidelines for managing exposed individuals. N-acetylcysteine (NAC) is a
      commercially available drug licensed in the UK and elsewhere for the treatment of
      paracetamol (acetaminophen) overdose. It has a number of mechanisms of action
      which may provide therapeutic benefit for the treatment of phosgene-induced ALI.
      It has previously been shown to provide therapeutic efficacy against the lung
      damaging effects of sulfur mustard vapour exposure, when given by the inhaled
      route, in the pig (Jugg et al., 2013). Our research objective was to determine
      whether inhaled NAC might also be therapeutic for other chemicals, in this case,
      phosgene. This study has demonstrated that multiple nebulised doses, administered
      from 30 min after exposure of terminally anaesthetised pigs to phosgene, is not
      an effective therapy when administered at the times and doses employed in this
      study. There remains no pharmacological treatment for phosgene-induced lung
      injury.

PMID- 29574135
TI  - Cryopreservation and in vitro culture of white-tailed deer ovarian tissue.
AB  - The aims of this study were to evaluate (1) the survivability of white-tailed
      deer ovarian tissue after cryopreservation by slow-freezing (SF) and
      vitrification (VIT) techniques and in vitro culture (IVC) for up to 7 days, and
      (2) the effects of cryopreservation techniques on protein expression of
      proliferative and apoptotic markers of ovarian tissue pre- and post-in vitro
      culture. Ovaries (n = 14) of seven white-tailed deer fawns (<1.5 years old) were
      used. Ovarian cortexes were cut into fragments (2 * 2 * 0.5 mm) and split into
      nine treatment groups: (1) fresh noncultured control, (2) fresh-IVC 1 day, (3)
      fresh-IVC 7 days, (4) SF noncultured, (5) SF-IVC 1 day, (6) SF-IVC 7 days, (7)
      VIT noncultured, (8) VIT-IVC 1 day, and (9) VIT-IVC 7 days. Preantral follicle
      morphology, class distribution, and density; stromal cell density; EGFR, Ki-67,
      Bax, and Bcl-2 protein expression; and DNA fragmentation were assessed. Results
      showed that: (i) white-tailed deer fresh ovarian tissue can be cultured for up to
      7 days, preserving the tissue integrity and 50% of morphologically normal
      preantral follicles; (ii) cryopreservation of white-tailed deer ovarian tissue by
      either slow-freezing or vitrification does not disrupt markers of proliferation
      and apoptosis after thawing; (iii) ovarian fragments cryopreserved by the
      vitrification method had greater follicle viability during in vitro culture than
      the slow-freezing method; and (iv) fragments cryopreserved by slow-freezing
      suffered apoptosis earlier than those preserved by vitrification. The findings
      herein reported advance knowledge towards development of adequate
      cryopreservation protocols for long-term banking programs for Cervidae species.

PMID- 29574136
TI  - Reply.

PMID- 29574137
TI  - A paired comparison study on refractive changes after strabismus surgery.

PMID- 29574138
TI  - Pediatric ocular injury secondary to a Burmese python bite.
AB  - We report the case of a 6-year-old girl with a penetrating ocular injury caused
      by a Burmese python. She received intravenous cefazolin before presenting and was
      treated thereafter with daily topical antibiotics and atropine. Six weeks after
      injury, she underwent cataract extraction and sulcus implantation of an
      intraocular lens and iris synechiolysis, with postoperative patching. Final
      visual outcome was excellent despite no globe repair was performed.

PMID- 29574139
TI  - Wuho/WDR4 deficiency inhibits cell proliferation and induces apoptosis via DNA
      damage in mouse embryonic fibroblasts.
AB  - Wuho known as WDR4 encodes a highly conserved WD40-repeat protein, which has
      known homologues of WDR4 in human and mouse. Wuho-FEN1 interaction may have a
      critical role in the growth and development, and in the maintenance of genome
      stability. However, how Wuho gene deletion contributes to cell growth inhibition
      and apoptosis is still unknown. We utilized CAGGCre-ER transgenic mice have a
      tamoxifen-inducible cre-mediated recombination cassette to prepare primary mouse
      embryonic fibroblasts (MEFs) with Wuho deficiency. We have demonstrated that Wuho
      deficiency would induces gammaH2AX protein level elevation, heterochromatin
      relaxation and DNA damage down-stream sequences, including p53 activation,
      caspase-mediated apoptotic pathway, and p21-mediated G2/M cell cycle arrest.

PMID- 29574141
TI  - Mathematical model of immune response to hepatitis B.
AB  - A new detailed mathematical model for dynamics of immune response to hepatitis B
      is proposed, which takes into account contributions from innate and adaptive
      immune responses, as well as cytokines. Stability analysis of different steady
      states is performed to identify parameter regions where the model exhibits
      clearance of infection, maintenance of a chronic infection, or periodic
      oscillations. Effects of nucleoside analogues and interferon treatments are
      analysed, and the critical drug efficiency is determined.

PMID- 29574140
TI  - Copy number variations of SCN5A in Brugada syndrome.
AB  - BACKGROUND: Loss-of-function mutations in SCN5A are associated in ~20% of Brugada
      syndrome (BrS) patients. Copy number variations (CNVs) have been shown to be
      associated with several inherited arrhythmia syndromes. OBJECTIVE: The purpose of
      this study was to investigate SCN5A CNVs among BrS probands. METHODS: The study
      cohort consisted of 151 BrS probands who were symptomatic or had a family history
      of BrS, sudden death, syncope, or arrhythmic diseases. We performed sequence
      analysis of SCN5A by the Sanger method. For detecting CNVs in SCN5A, we performed
      multiplex ligation-dependent probe amplification analysis of the 151 BrS
      probands. RESULTS: We identified pathogenic SCN5A mutations in 20 probands by the
      Sanger method. In 140 probands in whom multiplex ligation-dependent probe
      amplification was successfully performed, 4 probands were found to present
      different CNVs (deletion in 3 and duplication in 1). Three of them had fatal
      arrhythmia events; the remaining 1 was asymptomatic but had a family history.
      Mean age at diagnosis was 23 +/- 14 years. All of the baseline 12-lead
      electrocardiograms showed PQ-interval prolongation. The characteristics of these
      4 probands with CNVs were similar to those of the probands with mutations leading
      to premature truncation of the protein or missense mutations causing peak INa
      reduction >90%. CONCLUSION: We identified SCN5A CNVs in 2.9% of BrS probands who
      were symptomatic or had a family history.

PMID- 29574142
TI  - Exploring the interactions of EGFR with phosphorylated Mig6 by molecular dynamics
      simulations and MM-PBSA calculations.
AB  - Mig6, a negative regulator, directly binds to epidermal growth factor receptor
      (EGFR), including Mig6-segment1 and Mig6-segment2. Mig6 requires phosphorylation
      of Y394 on Mig6-segment2 in order to inhibit EGFR. Two phosphorylation pathways
      for Y394 have been previously reported and the first way may phosphorylate Y394
      primed by Y395 phosphorylation. Besides, the binding mechanism of phosphorylated
      Mig6-segment2 with EGFR has not been elucidated clearly. Focused on EGFR complex
      with phosphorylated Mig6-segment2, molecular dynamics (MD) simulations were
      performed to explore the interactions of Mig6-segment2 with EGFR. Our results
      indicate a probable phosphorylation pathway on Y394 and some key residues of EGFR
      play important roles in binding to phosphorylated Mig6-segment2. In addition, a
      special L-shaped structure was found to be possibly associated with irreversible
      inhibition of EGFR by Mig6. Our work can give meaningful information to better
      understand the phosphorylation pathways for Y394 and the interactions of EGFR
      binding to phosphorylated Mig6-segment2.

PMID- 29574143
TI  - Biosimilars: An opportunity. Position statement of the French Rheumatology
      Society (SFR) and Inflammatory Rheumatic Disease Club (CRI).

PMID- 29574144
TI  - Consensus paper on the "executive summary of the international conference on
      Mediterranean diet and health: a lifelong approach" an Italian initiative
      supported by the Mediterranean Diet Foundation and the Menarini Foundation.
AB  - The Mediterranean Diet Foundation, in collaboration with the International
      Menarini Foundation, organized the "International Conference on Mediterranean
      Diet and Health: A Lifelong Approach." The Conference was held in Ostuni (Puglia,
      Italy) from March 30 to April 1, 2017. The event received the endorsement of the
      American Federation for Aging Research, the Research Consortium "Luigi Amaducci,"
      the European Nutrition for Health Alliance, the European Union Geriatric Medicine
      Society, the Clinical Section of the International Association of Gerontology and
      Geriatrics-European Region, the National Research Council Research Project on
      Aging, the Italian Society of Gerontology and Geriatrics, and the Italian Society
      of Clinical Nutrition and Metabolism. During the conference, results were
      presented from major studies on dietary interventions aiming to assess the
      efficacy of the Mediterranean diet in the prevention of chronic diseases and the
      potential underlying mechanisms. Twenty-six international speakers, in seven
      different sessions, discussed the biological basis, clinical impact, health
      policy, and behavioral implications of the Mediterranean diet, and its use in
      potential interventions for health promotion.

PMID- 29574145
TI  - Identification of Indonesian clade 2.1 highly pathogenic influenza A(H5N1)
      viruses with N294S and S246N neuraminidase substitutions which further reduce
      oseltamivir susceptibility.
AB  - We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors
      of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated
      between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus
      Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility
      to oseltamivir and zanamivir. The NAs of four viruses were identified as extreme
      outliers to oseltamivir, based on statistical analysis by box plots, with IC50
      values ranging from 46 to 62 nM. The NAs of two of these viruses from Sumatra and
      Aceh, had an N294S substitution, while one virus from Sulawesi had an S246N NA
      substitution. The NAs of all four viruses showed a specific loss of slow binding
      to oseltamivir in an IC50 kinetics assay. As observed in our previous
      surveillance, there was only a minimal effect on the sensitivity to zanamivir or
      peramivir for these mutants or any of the other isolates tested. The continued
      circulation of subtype H5N1 viruses in avian species poses an on-going zoonotic
      threat. The fact that we continue to identify avian isolates with naturally
      occurring mutations conferring reduced oseltamivir susceptibility remains a
      concern, given oseltamivir will be a key antiviral in the event of a new pandemic
      emerging.

PMID- 29574146
TI  - A mathematical analysis of Prx2-STAT3 disulfide exchange rate constants for a
      bimolecular reaction mechanism.
AB  - Appreciation of peroxiredoxins as the major regulators of H2O2 concentrations in
      human cells has led to a new understanding of redox signaling. In addition to
      their status as the primary reducers of H2O2 to water, the oxidized peroxiredoxin
      byproduct of this reaction has recently been shown capable of participation in
      H2O2-mediated signaling pathways through disulfide exchange reactions with the
      transcription factor STAT3. The dynamics of peroxidase-transcription factor
      disulfide exchange reactions have not yet been considered in detail with respect
      to how these reactions fit into the larger network of competing reactions in
      human cells. In this study, we used a kinetic model of oxidation and reduction
      reactions related to H2O2 metabolism in the cytosol of human cells to study the
      dynamics of peroxiredoxin-2 mediated oxidation of the redox-regulated
      transcription factor STAT3. In combination with previously reported experimental
      data, the model was used to estimate the rate coefficient of a biomolecular
      reaction between Prx2 and STAT3 for two sets of assumptions that constitute lower
      and upper bound cases. Using these estimates, we calculated the relative rates of
      the reaction of oxidized peroxiredoxin-2 and STAT3 and other competing reactions
      in the cytosol. These calculations revealed that peroxiredoxin-2-mediated
      oxidation of STAT3 likely occurs at a much slower rate than competing reactions
      in the cytosol. This analysis suggests the existence of more complex mechanisms,
      potentially involving currently unknown protein-protein recognition partners,
      which facilitate disulfide exchange reactions between peroxiredoxin-2 and STAT3.

PMID- 29574147
TI  - Revisiting available knowledge on teleostean thyroid hormone receptors.
AB  - Teleosts are the most numerous class of living vertebrates. They exhibit great
      diversity in terms of morphology, developmental strategies, ecology and
      adaptation. In spite of this diversity, teleosts conserve similarities at
      molecular, cellular and endocrine levels. In the context of thyroidal systems,
      and as in the rest of vertebrates, thyroid hormones in fish regulate development,
      growth and metabolism by actively entering the nucleus and interacting with
      thyroid hormone receptors, the final sensors of this endocrine signal, to
      regulate gene expression. In general terms, vertebrates express the functional
      thyroid hormone receptors alpha and beta, encoded by two distinct genes (thra and
      thrb, respectively). However, different species of teleosts express thyroid
      hormone receptor isoforms with particular structural characteristics that confer
      singular functional traits to these receptors. For example, teleosts contain two
      thra genes and in some species also two thrb; some of the expressed isoforms can
      bind alternative ligands. Also, some identified isoforms contain deletions or
      large insertions that have not been described in other vertebrates and that have
      not yet been functionally characterized. As in amphibians, the regulation of some
      of these teleost isoforms coincides with the climax of metamorphosis and/or life
      transitions during development and growth. In this review, we aimed to gain
      further insights into thyroid signaling from a comparative perspective by
      proposing a systematic nomenclature for teleost thyroid hormone receptor isoforms
      and summarize their particular functional features when the information was
      available.

PMID- 29574148
TI  - alpha-Melanocyte-stimulating hormone promotes bone resorption resulting from
      increased osteoblastic and osteoclastic activities in goldfish.
AB  - We examined the effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on
      bone metabolism using regenerating goldfish scales. Normally developed scales on
      the bodies of goldfish were removed to allow the regeneration of scales under
      anesthesia. Thereafter, the influence of alpha-MSH on the regeneration of
      goldfish scales was investigated in vivo. In brief, alpha-MSH was injected at a
      low dose (0.1 MUg/g body weight) or a high dose (1 MUg/g body weight) into
      goldfish every other day. Ten days after removing the scales, we collected
      regenerating scales and analyzed osteoblastic and osteoclastic activities as
      respective marker enzyme (alkaline phosphatase for osteoblasts, tartrate
      resistant acid phosphatase for osteoclasts) activity in the regenerating scales
      as well as plasma calcium levels. At both doses, osteoblastic and osteoclastic
      activities in the regenerating scales increased significantly. Plasma calcium
      concentrations in the alpha-MSH-treated group (high doses) were significantly
      higher than those in the control group. Next, in vitro experiments were performed
      to confirm the results of in vivo experiments. In the cultured regenerating
      scales, osteoblastic and osteoclastic activities significantly increased with
      alpha-MSH (10-7 and 10-6 M) treatment. In addition, real-time PCR analysis
      indicated that osteoclastogenesis in alpha-MSH-treated scales was induced by the
      receptor activator of the NF-kappaB/receptor activator of the NF-kappaB
      ligand/osteoprotegerin pathway. Furthermore, we found that alpha-MSH receptors
      (melanocortin receptors 4 and 5) were detected in the regenerating scales. Thus,
      in teleosts, we are the first to demonstrate that alpha-MSH functions in bone
      metabolism and promotes bone resorption via melatonin receptors 4 and/or 5.

PMID- 29574149
TI  - Left-right pigmentation pattern of Japanese flounder corresponds to expression
      levels of melanocortin receptors (MC1R and MC5R), but not to agouti signaling
      protein 1 (ASIP1) expression.
AB  - Body coloration in flatfish is one of the most distinctive asymmetries in the
      animal kingdom, although the fundamental molecular mechanism of the pigmentation
      is unclear. In the dorso-ventral coloration (countershading) of other teleost
      fishes, ventral-specific expression of agouti signaling protein 1 (ASIP1), an
      endogenous antagonist of melanocortin 1 receptor (MC1R), has been reported to
      play a pivotal role. Contribution of ASIP1 is also suggested in the asymmetrical
      pigmentation of flatfish. In order to confirm the contribution of ASIP1 and
      further examine receptor function in the body coloration of Japanese flounder,
      expression levels of asip1, mc1r, melanocortin 5 receptor (mc5r), and melanin
      concentrating hormone receptor 2 (mchr2) were measured in the normally pigmented
      area of the left side, the normally non-pigmented area of the right side, and the
      abnormally pigmented (exhibiting hypermelanosis) area of the right side.
      Measurement was also carried out under conditions of hypermelanosis stimulated by
      cortisol and during the transition from non-pigmentation to pigmentation in areas
      of hypermelanosis. Contrary to our expectations, no difference was detected in
      asip1 expression between pigmented and non-pigmented areas. There was also no
      difference between normal and hormonally stimulated pigmented conditions in areas
      of hypermelanosis or during the transition process. Instead, the expression
      levels of mc1r, mc5r, and mchr2 were consistently higher in pigmented areas, and
      were especially increased under hormonally stimulated conditions. In addition,
      expressions of these receptor genes increased prior to pigmentation in areas of
      future hypermelanosis. Our results suggest that MC1Rand MC5R, but not necessarily
      ASIP1, contribute to pigmentation and hypermelanosis in Japanese flounder. We
      propose a yet unknown molecular mechanism for asymmetrical pigmentation in
      flatfish that is distinct from that of countershading in other vertebrates.

PMID- 29574150
TI  - Role of natriuretic peptide receptor 2-mediated signaling in meiotic arrest of
      zebrafish oocytes and its estrogen regulation through G protein-coupled estrogen
      receptor (Gper).
AB  - Natriuretic peptide type C (NPPC) and its receptor, natriuretic peptide receptor
      2 (NPR2), have essential roles in maintaining meiotic arrest of oocytes in
      several mammalian species. However, it is not known if a similar mechanism exists
      in non-mammalian vertebrates. Using zebrafish as a model, we show that Nppc is
      expressed in ovarian follicle cells, whereas Npr2 is mainly detected in oocytes.
      Treatment of intact and defolliculated oocytes with 100 nM NPPC for 6 h caused a
      large increase in cGMP concentrations, and a significant decrease in oocyte
      maturation (OM), an effect that was mimicked by treatment with 8-Br-cGMP.
      Treatment with E2 and G-1, the specific GPER agonist, also increased cGMP levels.
      Cyclic AMP levels were also increased by treatments with 8-Br-cGMP, E2 and G1.
      The estrogen upregulation of cAMP levels was blocked by co-treatment with AG1478,
      an inhibitor of EGFR activation. Gene expression of npr2, but not nppc, was
      significantly upregulated in intact oocytes by 6 h treatments with 20 nM E2 and G
      1. Both cilostamide, a phosphodiesterase 3 (PDE3) inhibitor, and rolipram, a PDE4
      inhibitor, significantly decreased OM of intact and defolliculated oocytes, and
      enhanced the inhibitory effects of E2 and G-1 on OM. These findings indicate the
      presence of a Nppc/Npr2/cGMP pathway maintaining meiotic arrest in zebrafish
      oocytes that is upregulated by estrogen activation of Gper. Collectively, the
      results suggest that Nppc through Npr2 cooperates with E2 through Gper in
      upregulation of cGMP levels to inhibit phosphodiesterase activity resulting in
      maintenance of oocyte meiotic arrest in zebrafish.

PMID- 29574151
TI  - Oviduct morphology and estrogen receptors ERalpha and ERbeta expression in
      captive Chinchilla lanigera (Hystricomorpha: Chinchillidae).
AB  - Chinchilla lanigera is a hystricomorph rodent from South America whose
      reproductive biology presents particular characteristics that distinguishes it
      from other Rodentia species, such as low reproductive rate, seasonal breeding
      pattern, and long estrous cycle. Nevertheless, reproductive features in female
      chinchillas are still poorly investigated, with a scarce knowledge concerning the
      estrous cycle and the histology of reproductive organs. In this study, we
      investigate the morphology, histomorphometry, secretory activity, and
      immunolocalization of estrogen receptors ERalpha and ERbeta in oviducts of
      nulliparous chinchillas, euthanized at fall season in Brazil. Follicular phase of
      estrous cycle of all studied animals was characterized by ovary and uterine
      morphology inspection, as well as vaginal cytology. Similar to other mammals, the
      oviduct wall of infundibulum, ampulla and isthmus was composed of mucosa, muscle,
      and serosa layers. Morphometric data of oviduct layers were used for identifying
      each oviduct segment. In the follicular phase, the oviduct was characterized by
      intense secretory activity, mainly in the ampulla, and expression of ERalpha and
      ERbeta throughout the oviduct epithelium. Both ERalpha and ERbeta were also
      detected in the connective tissue and smooth muscle cells. Our findings point out
      to the important role of estrogen in this female organ. Similar wide distribution
      of both ER proteins has been described for human Fallopian tube. Taken together,
      our data add to the understanding of the reproductive biology of female
      chinchillas, and may assist in the intensive breeding of this species and any
      eventual endeavor for conservation of chinchillas in the wild.

PMID- 29574152
TI  - The advantages of introducing aripiprazole once-monthly 300 mg in the bipolar
      disorder-II maintenance treatment regime for 2 patients.

PMID- 29574153
TI  - Inhibition of KLHL21 prevents cholangiocarcinoma progression through regulating
      cell proliferation and motility, arresting cell cycle and reducing Erk
      activation.
AB  - Kelch-like family member 21 (KLHL21) is involved in cell mitosis and motility.
      Nevertheless, the clinical significance and biological function of KLHL21 in
      cholangiocarcinoma (CCA) are elusive. This is the first study to describe a
      pivotal role for KLHL21 in the progression of CCA. The expression of KLHL21 was
      elevated in CCA tissues compared with paired normal bile duct tissues. In
      addition, immunohistochemical and statistical analyses demonstrated that the
      expression of KLHL21 correlated inversely with tumor histological grade (p <
      0.05) and the overall survival of patients (p < 0.01). In CCA cells, we found
      that the inhibition of KLHL21 significantly reduced proliferation, migration and
      invasion. Further results indicated that inhibition of KLHL21 triggered G0/G1
      cell cycle arrest, leading to the increased expression of P21 and P27 and
      decreased expression of Cyclin E1, which eventually resulted in proliferation
      suppression in CCA cells. Furthermore, KLHL21 knockdown alleviated the activation
      of the Erk signaling pathway via decreasing the expression of phospho-Erk1/2. Our
      data demonstrated that KLHL21 plays an essential role in the tumorigenesis and
      progression of CCA, implying that it might serve as a potential therapeutic
      target for CCA treatment.

PMID- 29574154
TI  - PDLIM5 identified by label-free quantitative proteomics as a potential novel
      biomarker of papillary thyroid carcinoma.
AB  - In order to better understand the mechanisms underlying the development of
      papillary thyroid carcinoma (PTC), and to identify new potential biomarkers, high
      resolution label-free mass spectrometry was performed on PTC tissues and adjacent
      normal thyroid tissues from six patients. In this process, 2788 proteins were
      identified, out of which 49 proteins presented significant differences between
      PTC tissues and adjacent normal thyroid tissues. Gene ontology revealed that the
      majority of these proteins are involved in the catalytic activity and binding. We
      selected three proteins with differential expressions: PDZ and LIM domain 5
      (PDLIM5), PDLIM1 and ALDH1A1; Protein expressions were further verified by RT-PCR
      and western blot. Among these, expression of PDLIM5 and PDLIM1 was up-regulated,
      while that of ALDH1A1 was down-regulated in PTC tissues. Next, we confirmed their
      expression through quantitative dot blot (QDB) technique. We found that knockdown
      of PDLIM5 expression in the B-CPAP cell line could inhibit the migration,
      invasion and proliferation of PTC cells. In addition, PDLIM5 knockdown reduced
      Ras and Phospho-ERK1/2 expression. Thus, we suggested that PDLIM5 promotes PTC
      via activation of the Ras-ERK pathway. Our research provides new molecular
      insight into the function of PDLIM5, which may assist in studying the mechanism
      of PTC. In addition, PDLIM5 could be further explored as a potential candidate
      for PTC treatment.

PMID- 29574155
TI  - Autophagy is involved in the protective effect of endophilin A2 on H2O2-induced
      apoptosis in H9C2 cardiomyocytes.
AB  - Apoptosis plays a critical role in normal embryonic development and tissue
      homeostasis regulation. EndophilinA2 (EndoA2) is widely reported to regulate
      endocytosis. Additionally, EndoA2 has been demonstrated to be involved in tumor
      metastasis, neuroregulation and vascular function. In this study, we used siRNA
      and Ad-EndoA2 transfection strategy to investigate whether EndoA2 provides a
      protective effect against apoptosis induced by H2O2 in H9C2 cardiomyocytes and
      the underlying mechanisms. We found that EndoA2 siRNA knockdown promoted H2O2
      induced apoptosis in H9C2 cardiomyocytes, evidenced by decreased cell number,
      increased apoptotic cells, and activation of caspase-3. In contrast, EndoA2
      overexpression showed the opposite effects and inhibited H2O2-induced apoptosis
      in H9C2 cardiomyocytes. Further studies revealed that EndoA2 overexpression
      strengthened autophagy, evidenced by the increased LC3 II/I ratio and P62
      degradation, whereas EndoA2 siRNA knockdown produced the opposite effects.
      Furthermore, we revealed that there was an interaction between Bif-1 and Beclin
      1. Upon H2O2 treatment, the association of Bif-1 and Beclin-1 remarkably
      increased. EndoA2 overexpression further promoted the binding of Bif-1 with
      Beclin-1, whereas EndoA2 siRNA knockdown reduced this association. These data
      strongly suggested that EndoA2 inhibited H2O2-induced apoptosis in H9C2
      cardiomyocytes, possibly by promoting Bif-1 to form a complex with Beclin-1 and
      strengthening autophagy. This study provides a novel target for heart diseases.

PMID- 29574156
TI  - Serum extracellular vesicles promote proliferation of H9C2 cardiomyocytes by
      increasing miR-17-3p.
AB  - Emerging evidence showed that cardiac proliferation played a significant role in
      the cardiac rehabilitation and repair. Extracellular vesicles (EVs) are known to
      regulate multiple cell functions, whereas the role of EVs in cardiac
      proliferation still remains unclear. In this study, we found that serum EVs
      promoted cell proliferation in rat heart myoblastic H9C2 cells with significantly
      increased expression level of miR-17-3p. Inhibition of miR-17-3p could decrease
      H9C2 cells proliferation induced by serum EVs. Additionally, we found that TIMP3
      was a target of miR-17-3p in H9C2 cells proliferation and the expression of TIMP3
      was downregulated by serum EVs. Meanwhile, inhibition of TIMP3 increased cardiac
      proliferation. In conclusion, results of our study indicated that serum EVs could
      promote the proliferation of H9C2 cells via regulating miR-17-3p/TIMP3, which may
      be a potential therapeutic target for treatment of cardiac injury.

PMID- 29574157
TI  - Interleukin-23 promotes the migration and invasion of gastric cancer cells by
      inducing epithelial-to-mesenchymal transition via the STAT3 pathway.
AB  - Chronic inflammation is associated with all stages of cancer development.
      Moreover, a proinflammatory microenvironment resulted from chronic inflammation
      is considered to be an essential component of cancer. Interleukin-23 (IL-23) is a
      general proinflammatory factor; and is involved in tumor-associated inflammation
      in gastric cancer (GC). However, the direct effect of IL-23 on GC cells has been
      rarely reported. The aim of the study was to clarify the direct role of IL-23 in
      regulating GC progression, and to identify the underlying mechanism. In this
      study, Positive expression of IL-23R was observed in GC tissues and cell lines by
      using immunohistochemistry or immunofluorescence. In western blots, the
      expression of IL-23R was higher in GC tissues compared with adjacent normal
      tissues. Furthermore, IL-23R positive GC tissues were closely related with larger
      tumor size and worse T stage and clinical stage. By performing in vitro
      experiments, we found that IL-23 binding to its receptor promoted the migration
      and invasion of BGC-823 cells in vitro. Moreover, IL-23 induced the activation of
      STAT3 and epithelial-to-mesenchymal transition (EMT) in BGC-823 cells. Knocking
      down STAT3 in BGC-823 cells attenuated the effect of IL-23 on EMT and cell
      migration and invasion. Taken together, our study has firstly demonstrated the
      positive expression of IL-23R in human GC tissues and cell lines. IL-23 binding
      to its receptor promotes the migration and invasion of GC cells by inducing EMT
      through the STAT3 signaling pathway. This work provides a new mechanism for the
      oncogenic role of IL-23 on GC progression.

PMID- 29574158
TI  - CsTFL1b may regulate the flowering time and inflorescence architecture in
      cucumber (Cucumis sativus L.).
AB  - Cucumber is an important vegetable with indeterminate growth habit which is
      beneficial to its yield. In this study, we cloned the TFL1 homolog CsTFL1b in
      cucumber. CsTFL1b shares highly sequence similarity to TFL1 from Arabidopsis and
      has conservative histidine amino acid residue which is necessary for TFL1
      function. However, phylogenetic analysis suggested that cucurbits TFL1s (CsTFL1b
      of cucumber and CmTFL1 of melon) formed a subclade which is far from the AtTFL1
      in Arabidopsis or CEN in Antirrhinum. CsTFL1b was highest expressed in male
      flower but barely expressed in SAM which was different from TFL1 in Arabidopsis
      with highly transcription accumulation in SAM and CsTFL1b was located in nucleus
      and cytoplasm. Upon ectopic expression of CsTFL1b in Arabidopsis, the flowering
      time of transgenic plants was significantly delayed in both wild type and tfl1-11
      mutant background but the terminal flower phenotype of tfl1-11 mutant was
      partially rescued. These results may underlie the discrepant function of CsTFL1b
      in cucumber from that in Arabidopsis.

PMID- 29574159
TI  - miR-126-5p targets Malate Dehydrogenase 1 in non-small cell lung carcinomas.
AB  - Malate Dehydrogenase (MDH) 1 has recently been shown to be highly expressed and
      display prognostic value in non-small cell lung carcinomas (NSCLCs). However, it
      is not known how MDH1 expression is regulated and there is no current molecular
      or chemical strategy that specifically targets MDH1. This may be due to
      structural and enzymatic similarities with its isoenzyme, malate dehydrogenase 2
      (MDH2). However, MDH1 and MDH2 are encoded by distinct genes and this opens up
      the possibility for modulation at the expression level. Here, we screened in
      silico for microRNAs (miRs) that selectively targets the 3'UTR region of MDH1.
      These analyses revealed that mir-126-5p has three binding sites in the 3'UTR
      region of MDH1. Additionally, we show that expression of miR-126-5p suppresses
      the enzymatic activity of MDH1, mitochondrial respiration and caused cell death
      in NSCLC cell lines.

PMID- 29574160
TI  - Reactive oxygen species participate in liver function recovery during
      compensatory growth in zebrafish (Danio rerio).
AB  - Compensatory growth (CG) is defined as a phase of accelerated growth when the
      disadvantageous environment is improved, accompanied by metabolic adjustment.
      Here, we report that hepatic oxidative phosphorylation (OXPHOS) activity was
      enhanced during compensatory growth in zebrafish. Mitochondrial metabolism
      enabled the generation of reactive oxygen species (ROS), which activated the nrf2
      (nuclear factor-erythroid 2-related factor 2) signaling pathway, as well as the
      mTOR signaling pathway. Tempol (a superoxide dismutase mimetic) treatment blocked
      ROS signaling in the liver as well as CG in zebrafish. These results demonstrated
      that mitochondrial ROS signaling are essential for the occurrence of compensatory
      growth in zebrafish.

PMID- 29574162
TI  - Surgical treatment in bone metastases in the appendicular skeleton.
AB  - INTRODUCTION: Metastatic bone disease is the most common neoplastic process that
      affects the skeletal system. Eighty percent of bone metastases come from
      carcinomas of the breast, lung, kidney, thyroid and prostate. The Katagiri scale
      enables an estimation of the survival of patients based on the presence or
      absence of visceral metastases, multiple bone metastases and functional status
      according to the ECOG scale. MATERIAL AND METHODS: A retrospective, descriptive
      and observational study conducted between March 1, 2013 and June 30, 2015. Thirty
      two patients were studied with a diagnosis of metastatic bone disease and who had
      undergone some type of orthopaedic surgical treatment for pathological fracture
      or impending fracture. RESULTS: 28 cases (87.5%) presented pathological fracture
      and 4 cases (12.5%) impending fracture according to the Mirels score. Fifteen
      cases (46.875%) were treated by placing a central medullary nail + spacer in the
      long bone diaphysis, 15 cases (46.875%) with modular arthroplasties and 2
      patients (6.25%) with forequarter amputation. Eleven patients (34.375%) died
      during the course of this study, all with a Katagiri greater than or equal to 4.
      DISCUSSION: The presence of a fracture in previously damaged territory is a
      catastrophic complication for most cancer patients. A clear understanding of the
      life expectancy of patients with bone metastases is of great help to prevent
      errors and failures in treatment.

PMID- 29574161
TI  - Comparison of functional results of two fixation systems using single-row
      suturing of rotator cuff.
AB  - INTRODUCTION: Arthroscopic repair of rotator cuff disorders is a technically
      demanding but successful procedure. Many anchor and suture alternatives are now
      available. The choice of the implant by the surgeon is less important than the
      configuration of the suture used to fix the tendon, however it is necessary to
      know if there are differences in the results, using each one of them. The aim of
      the study is to evaluate if there are differences between the knotted and non
      knotted implant in terms of functional and satisfaction results. MATERIAL AND
      METHODS: A retrospective study was carried out on 83 patients operated between
      2010 and 2014 in our center using 2anchoring systems with and without knotting
      (39 versus 44 patients respectively), with single row in complete rupture of the
      rotator cuff. RESULTS: At the end of the follow-up, an average score was obtained
      on the Constant scale of 74.6 points. 98% of the patients considered the result
      of the surgery satisfactory. Statistically, there were no significant differences
      between the 2groups in terms of functionality, satisfaction or reincorporation to
      activities. DISCUSSION AND CONCLUSIONS: The functional results of the single-row
      cuff suture are satisfactory, although biomechanical studies show advantages in
      favor of sutures that reproduce a transoseo system. It our series of patients the
      presence of knotting does not show per se a significant functional difference
      being both superimposable techniques in absolute values of functionality and
      patient satisfaction.

PMID- 29574163
TI  - Tibial tunnel widening associated with anterior cruciate ligament reconstruction
      using autogenous hamstrings: A comparison between antero-medial portal and
      transtibial techniques.
AB  - OBJECTIVE: Evaluate the enlargement effect of the tibial tunnel emergence of 2
      different of anterior cruciate ligament reconstruction techniques: antero-medial
      portal (AMP) vs. transtibial (TT) technique. METHODS: A prospective, randomized
      controlled study was performed in 36 consecutive patients who underwent anterior
      cruciate ligament reconstruction with autologous hamstring tendon grafts
      employing the AMP and conventional TT techniques. Lateral and antero-posterior
      radiographs were obtained for each patient at 6 weeks and 12 months
      postoperatively. The sclerotic margins of the tibial tunnels were measured at the
      widest dimension of the tunnel as well as the diameter of the tibial emergence
      and were compared with the initially drilled tunnel size after correction for
      radiographic magnification. Statistical analysis was performed to compare the 2
      groups by use of the independent-samples t test, with significance set at .05.
      RESULTS: The mean percentage increase in the diameter of tibial tunnel emergence
      at 6 weeks after surgery was 8.1%+/-2.9 for the PAM technique and 21.20%+/-11.87
      for the TT technique on the anteroposterior x-ray view. However, the mean
      percentage increase in the diameter of the tibial tunnel emergence on the lateral
      view was 7.1%+/-4.72 for the medial portal technique and 17.64%+/-11.48 for the
      transtibial technique. This difference was statistically significant on both
      anteroposterior and lateral views. CONCLUSIONS: The diameter of the tibial tunnel
      emergence for hamstring autologous anterior cruciate ligament reconstructions was
      significantly lower for the medial portal technique when compared with the
      conventional TT technique.

PMID- 29574164
TI  - Phylodynamic analysis and molecular diversity of the avian infectious bronchitis
      virus of chickens in Brazil.
AB  - Avian infectious bronchitis virus (IBV) is the etiological agent of a highly
      contagious disease, which results in severe economic losses to the poultry
      industry. The spike protein (S1 subunit) is responsible for the molecular
      diversity of the virus and many sero/genotypes are described around the world.
      Recently a new standardized classification of the IBV molecular diversity was
      conducted, based on phylogenetic analysis of the S1 gene sequences sampled
      worldwide. Brazil is one of the biggest poultry producers in the world and the
      present study aimed to review the molecular diversity and reconstruct the
      evolutionary history of IBV in the country. All IBV S1 gene sequences, with local
      and year of collection information available on GenBank, were retrieved.
      Phylogenetic analyses were carried out based on a maximum likelihood method for
      the classification of genotypes occurring in Brazil, according to the new
      classification. Bayesian phylogenetic analyses were performed with the Brazilian
      clade and related international sequences to determine the evolutionary history
      of IBV in Brazil. A total of 143 Brazilian sequences were classified as GI-11 and
      46 as GI-1 (Mass). Within the GI-11 clade, we have identified a potential
      recombinant strain circulating in Brazil. Phylodynamic analysis demonstrated that
      IBV GI-11 lineage was introduced in Brazil in the 1950s (1951, 1917-1975 95% HPD)
      and population dynamics was mostly constant throughout the time. Despite the
      national vaccination protocols, our results show the widespread dissemination and
      maintenance of the IBV GI-11 lineage in Brazil and highlight the importance of
      continuous surveillance to evaluate the impact of currently used vaccine strains
      on the observed viral diversity of the country.

PMID- 29574165
TI  - Acupuncture for the Treatment of Paraneoplastic Night Sweats.
AB  - This case report describes acupuncture treatment to manage paraneoplastic night
      sweating secondary to pancreatic cancer. A 56-year-old gentleman with a 2-month
      history of night sweating responded well over a 10-week course of acupuncture
      treatment. Acupuncture was selected for symptom management after no success was
      achieved with pharmacological and conventional managements. The severity of night
      sweating had reduced from 9/10 to 1/10 on visual analog scale at the end of
      treatment. This case report suggests that acupuncture has a favorable effect on
      paraneoplastic night sweating in patients with advanced pancreatic cancer and
      recommends further research.

PMID- 29574166
TI  - Stem cells from apical papilla promote differentiation of human pluripotent stem
      cells towards retinal cells.
AB  - Recently, we have found that human stem cells from apical papilla (SCAP) show a
      stromal cell-derived inducing activity (SDIA). To examine SDIA competence for
      retinal cells differentiation, we co-cultured SCAP with human pluripotent stem
      cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly
      induces hPSCs to differentiate into rostral neural cells as demonstrated by
      upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8.
      Furthermore, the differentiated cells on SCAP significantly expressed eye-field
      markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies. The
      generated hPSC-retinal pigmented epithelium (RPE) was hexagonal and highly
      expressed related markers, ZO-1, RPE65, BEST, CRALBP and MITF. They were able to
      phagocytose latex beads. Moreover, the assessment of the isolated neural tube
      like structures on SCAP showed the expression of retinal progenitor cells (RPCs) 
      SIX3, RAX, and PAX6. SCAP highly expressed DKK3 and SFRP2, Wnt inhibitor factors
      and their target genes, Cyclin D1 and c-Myc were down-regulated significantly on
      SCAP. These results showed SCAP promoted the differentiation of hPSCs into
      retinal cells (RPE and RPCs) possibly through inhibition of Wnt signaling
      pathway. This simple and efficient approach provides human RPE generation for
      developing therapies for diseases such as age-related macular degeneration.

PMID- 29574167
TI  - People with low back pain perceive needs for non-biomedical services in
      workplace, financial, social and household domains: a systematic review.
AB  - QUESTION: What needs of non-biomedical services are perceived by people with low
      back pain? DESIGN: Systematic review of qualitative and quantitative studies
      examining perceived needs of non-biomedical services for low back pain,
      identified through searching of MEDLINE, EMBASE, CINAHL and PsycINFO (1990 to
      2016). PARTICIPANTS: Adults with low back pain of any duration. DATA EXTRACTION
      AND ANALYSIS: Descriptive data regarding study design and methodology were
      extracted. The preferences, expectations and satisfaction with non-biomedical
      services reported by people with low back pain were identified and categorised
      within areas of perceived need. RESULTS: Twenty studies (19 qualitative and one
      quantitative) involving 522 unique participants (total pool of 590) were included
      in this systematic review. Four areas emerged. Workplace: people with low back
      pain experience pressure to return to work despite difficulties with the demands
      of their occupation. They want their employers to be informed about low back pain
      and they desire workplace accommodations. Financial: people with low back pain
      want financial support, but have concerns about the inefficiencies of
      compensation systems and the stigma associated with financial remuneration.
      Social: people with low back pain report feeling disconnected from social
      networks and want back-specific social support. Household: people with low back
      pain report difficulties with household duties; however, there are few data
      regarding their need for auxiliary devices and domestic help. CONCLUSION: People
      with low back pain identified work place, financial and social pressures, and
      difficulties with household duties as areas of need beyond their healthcare
      requirements that affect their ability to comply with management of their
      condition. Consideration of such needs may inform physiotherapists, the wider
      health system, social networks and the workplace to provide more relevant and
      effective services. [Chou L, Cicuttini FM, Urquhart DM, Anthony SN, Sullivan K,
      Seneviwickrama M, Briggs AM, Wluka AE (2018) People with low back pain perceive
      needs for non-biomedical services in workplace, financial, social and household
      domains: a systematic review. Journal of Physiotherapy 64: 74-83].

PMID- 29574168
TI  - Low leisure-based sitting time and being physically active were associated with
      reduced odds of death and diabetes in people with chronic obstructive pulmonary
      disease: a cohort study.
AB  - QUESTIONS: In people with chronic obstructive pulmonary disease (COPD), are
      activity phenotypes (based on physical activity and recreational screen time)
      associated with mortality and cardiometabolic risk factors? DESIGN: Cohort study.
      PARTICIPANTS: People with COPD aged>=40years and who were current or ex-smokers
      were identified from the 2003 Scottish Health Survey. OUTCOME MEASURES: Data were
      collected regarding demographics, anthropometric measurements, medical history,
      physical activity, sedentary behaviour, health outcomes, and mortality. ANALYSIS:
      Participants were categorised into one of the following activity phenotypes:
      'couch potatoes' were those who were insufficiently active with high leisure
      based sitting time and/or no domestic physical activity; 'light movers' were
      insufficiently active with some domestic physical activity; 'sedentary
      exercisers' were sufficiently active with high leisure-based sitting time; and
      'busy bees' were sufficiently active with low leisure-based sitting time.
      'Sufficiently active' was defined as adhering to physical activity (PA)
      recommendations of>=7.5 metabolic equivalent (MET) hours/week. 'Low leisure-based
      sitting time' was defined as<=200minutes of recreational screen time/day.
      RESULTS: The 584 participants had a mean age of 64 years (SD 12) and 52% were
      male. Over 5.5 years (SD 1.3) of follow-up, there were 81 all-cause deaths from
      433 COPD participants with available data. Compared to the 'couch potatoes',
      there was a reduced risk of all-cause mortality in the 'busy bees' (Hazard Ratio
      0.26, 95% CI 0.11 to 0.65) with a trend towards a reduction in mortality risk in
      the other phenotypes. The odds of diabetes were lower in the 'busy bees' compared
      to the 'couch potatoes' (OR 0.14, 95% CI 0.03 to 0.67). CONCLUSIONS: Adhering to
      physical activity guidelines and keeping leisure-based sitting time low had a
      mortality benefit and lowered the odds of diabetes in people with COPD. [McKeough
      Z, Cheng SWM, Alison J, Jenkins C, Hamer M, Stamatakis E (2018) Low leisure-based
      sitting time and being physically active were associated with reduced odds of
      death and diabetes in people with chronic obstructive pulmonary disease: a cohort
      study. Journal of Physiotherapy 64: 114-120].

PMID- 29574169
TI  - Appraisal of Clinical Practice Guideline: Management of neck pain.

PMID- 29574170
TI  - An education program about pelvic floor muscles improved women's knowledge but
      not pelvic floor muscle function, urinary incontinence or sexual function: a
      randomised trial.
AB  - QUESTION: Does an educational program with instructions for performing 'the
      Knack' improve voluntary contraction of the pelvic floor muscles, reduce reports
      of urinary incontinence, improve sexual function, and promote women's knowledge
      of the pelvic floor muscles? DESIGN: Randomised, controlled trial with concealed
      allocation, intention-to-treat analysis and blinded assessors. PARTICIPANTS:
      Ninety-nine women from the local community. INTERVENTION: The experimental group
      (n=50) received one lecture per week for 4 weeks, and instructions for performing
      'the Knack'. The control group (n=49) received no intervention. OUTCOME MEASURES:
      The primary outcome was maximum voluntary contraction of the pelvic floor muscles
      measured using manometry. Secondary outcomes were: ability to contract the pelvic
      floor muscles measured using vaginal palpation; severity of urinary incontinence
      measured by the International Consultation on Incontinence Questionnaire-Short
      Form (ICIQ-SF) scored from 0 to 21; self-reported sexual function; and knowledge
      related to the pelvic floor. Outcomes were measured at baseline and after 4
      weeks. RESULTS: The intervention did not significantly improve: maximum voluntary
      contraction (MD 2.7 cmH2O higher in the experimental group, 95% CI -0.5 to 5.9);
      ability to contract the pelvic floor muscles (RR 2.18, 95% CI 0.49 to 9.65); or
      self-reported severity of urinary incontinence (MD 1 point greater reduction in
      the experimental group, 95% CI -3 to 1). Sexual function did not significantly
      differ between groups, but very few of the women engaged in sexual activity
      during the study period. The educational program did, however, significantly
      increase women's knowledge related to the location, functions and dysfunctions of
      the pelvic floor muscles, and treatment options. CONCLUSION: Education and
      teaching women to perform 'the Knack' had no significant effect on voluntary
      contraction of the pelvic floor muscles, urinary incontinence or sexual function,
      but it promoted women's knowledge about the pelvic floor. TRIAL REGISTRATION:
      Brazilian Registry of Clinical Trials, RBR-95sxqv. [de Andrade RL, Bo K, Antonio
      FI, Driusso P, Mateus-Vasconcelos ECL, Ramos S, Julio MP, Ferreira CHJ (2018) An
      education program about pelvic floor muscles improved women's knowledge but not
      pelvic floor muscle function, urinary incontinence or sexual function: a
      randomised trial. Journal of Physiotherapy 64: 91-96].

PMID- 29574171
TI  - The impact of tumor cell metabolism on T cell-mediated immune responses and
      immuno-metabolic biomarkers in cancer.
AB  - The role of adaptive immunity is increasingly recognized as an important element
      both in the process of tumorigenesis and in the patient's response to treatment.
      While this understanding has led to new therapeutic strategies that potentiate
      the activities of tumor infiltrating lymphocytes, only a minority of patients
      attain durable responses. Metabolic activities in the tumor microenvironment,
      including hypoxia and acidity, can adversely affect immune responses, making the
      identification of metabolic biomarkers critically important for understanding and
      employing immunotherapies.

PMID- 29574172
TI  - Concentration of the CDCP1 protein in human cord plasma may serve as a predictor
      of hematopoietic stem and progenitor cell content.
AB  - Successful hematopoietic stem and progenitor cell (HSPC) transplantation rests
      upon reliable methods for their enumeration in sources such as cord blood (CB).
      Methods used today are costly, time consuming and exhaust the limited number of
      cells needed for transplantation. The aim of this study was to analyze if surplus
      plasma from CB contains biomarkers that can predict HSPC content in CB. Frozen,
      surplus plasma from 95 CB units was divided into two groups based on CD34+ cell
      concentration. Birth weight, gestation age, gender, mode of delivery, collection
      volume, nucleated cell count and colony forming unit assay results were
      available. Samples were analyzed with a proximity ligation assay covering 92
      different proteins. Two-group t-test with p-values adjusted for false discovery
      rate (FDR) identified 5 proteins that significantly differed between the two
      groups. CDCP1 was the most significant (FDR adjusted p-value 0.006). Correlation
      with CDCP1 concentration was most significant for CD34+ concentration and
      nucleated cell count. Multivariate analysis showed that CD34 and gender seemed to
      influence the level of CDCP1. In conclusion, CDCP1 was identified as a potential
      biomarker of HSPC content in CB. The finding also warrants further investigation
      for a possible role of CDCP1 in regulating HSPC presence in CB.

PMID- 29574173
TI  - Generation of induced pluripotent stem cell line (ZZUi011-A) from urine sample of
      a normal human.
AB  - Urine cells collected from 200mL clean midsection urine of a 25-year-old healthy
      man were reprogrammed into pluripotent stem cells via Sendai virus delivery
      system. The induced pluripotent stem cells showed a normal karyotype and
      exhibited the potential to differentiate into three germ layers in a teratoma
      assay. This cell line may serve as a useful control for comparison with other
      pluripotent stem cell lines induced from somatic cells of patients with genetic
      neurodegenerative disorders.

PMID- 29574174
TI  - Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate
      the CD8+ T cell response.
AB  - Myeloid-derived suppressor cells (MDSCs) are markedly increased in cancer
      patients and tumor-bearing mice and promote tumor growth and survival by
      inhibiting host innate and adaptive immunity. In this study, we generated and
      characterized MDSCs from murine-induced pluripotent stem cells (iPSCs). The iPSCs
      were co-cultured with OP9 cells, stimulated with GM-CSF, and became
      morphologically heterologous under co-culturing with hepatic stellate cells.
      Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have
      a T-cell regulatory function. Furthermore, a popliteal lymph node assay and
      autoimmune hepatitis model showed that iPS-MDSCs also regulate immune
      responsiveness in vivo and have a therapeutic effect against hepatitis. Taken
      together, our results demonstrated a method of generating functional MDSCs from
      iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource
      for transplantation and autoimmune diseases.

PMID- 29574175
TI  - Developing Process Maps as a Tool for a Surgical Infection Prevention Quality
      Improvement Initiative in Resource-Constrained Settings.
AB  - BACKGROUND: Surgical infections cause substantial morbidity and mortality in low
      and middle-income countries (LMICs). To improve adherence to critical
      perioperative infection prevention standards, we developed Clean Cut, a checklist
      based quality improvement program to improve compliance with best practices. We
      hypothesized that process mapping infection prevention activities can help
      clinicians identify strategies for improving surgical safety. STUDY DESIGN: We
      introduced Clean Cut at a tertiary hospital in Ethiopia. Infection prevention
      standards included skin antisepsis, ensuring a sterile field, instrument
      decontamination/sterilization, prophylactic antibiotic administration, routine
      swab/gauze counting, and use of a surgical safety checklist. Processes were
      mapped by a visiting surgical fellow and local operating theater staff to
      facilitate the development of contextually relevant solutions; processes were
      reassessed for improvements. RESULTS: Process mapping helped identify barriers to
      using alcohol-based hand solution due to skin irritation, inconsistent
      administration of prophylactic antibiotics due to variable delivery outside of
      the operating theater, inefficiencies in assuring sterility of surgical
      instruments through lack of confirmatory measures, and occurrences of retained
      surgical items through inappropriate guidelines, staffing, and training in proper
      routine gauze counting. Compliance with most processes improved significantly
      following organizational changes to align tasks with specific process goals.
      CONCLUSIONS: Enumerating the steps involved in surgical infection prevention
      using a process mapping technique helped identify opportunities for improving
      adherence and plotting contextually relevant solutions, resulting in superior
      compliance with antiseptic standards. Simplifying these process maps into an
      adaptable tool could be a powerful strategy for improving safe surgery delivery
      in LMICs.

PMID- 29574176
TI  - Incidental Hypercalcemia and the Parathyroid.

PMID- 29574177
TI  - Robotic-Assisted Lobectomies in the National Cancer Database.
AB  - BACKGROUND: Robotic-assisted thoracoscopic surgery (RobATS) lobectomy is becoming
      more common for the treatment of lung cancer. As with any relatively new
      technology, there is the assumption that greater experience leads to greater
      proficiency. The objective of this study was to analyze outcomes of patients
      undergoing RobATS lobectomy as hospitals gain experience, and to describe
      outcomes after conversion to open procedures. STUDY DESIGN: The National Cancer
      Database (NCDB) was used to analyze robotic lobectomies for lung cancer from 2010
      to 2014. Individual hospitals were categorized by the year they began reporting
      robotic lobectomies to the NCDB. Primary outcomes were perioperative morbidity
      and mortality and rate of conversion to open lobectomy. RESULTS: There were 7,645
      robotic lobectomies identified from 465 hospitals. The overall conversion rate
      was 9.2% (n = 702). A propensity-matched analysis showed no significant
      difference between experienced and inexperienced hospitals with respect to 30-day
      mortality (1.07% vs 2.03%, p = 0.092) or 90-day mortality (2.35% vs 3.63%, p =
      0.104). Conversion to open was a predictor of 30-day mortality (odds ratio [OR]
      2.54, CI 1.56 to 4.14) and 90-day mortality (OR 2.68, CI 1.83 to 3.91). Patients
      who underwent conversion had higher 90-day mortality compared with patients not
      undergoing conversion, in years of experience: 2 (p = 0.043), 3 (p = 0.002), and
      4 (p = 0.003). CONCLUSIONS: Mortality after RobATS lobectomy at experienced
      hospitals is not significantly different than at inexperienced hospitals. Though
      conversion rates decrease with experience, patients who undergo conversion have
      higher mortality than those who do not, particularly in hospitals with more
      experience. This suggests that a deliberate effort to increase experience with
      and improve patient selection for RobATS lobectomies may ameliorate the
      conversions and their attendant sequelae.

PMID- 29574178
TI  - Proposal of Prognostic Survival Models before and after Liver Resection for
      Hepatocellular Carcinoma in Potentially Transplantable Patients.
AB  - BACKGROUND: Transplantable hepatocellular carcinoma (HCC) represents a highly
      debated issue due to the overlap between indications for liver resection (LR) and
      transplantation (LT) in patients suitable for both. STUDY DESIGN: Between January
      2000 and December 2012, five hundred and twenty-four transplantable patients
      affected by HCC were identified among resected patients. Two regression models
      were constructed to classify patients into 2 groups pre-low and pre-high risk
      based on preoperative variables and then to reclassify pre-low-risk patients
      according to postoperative variables into either post-low or post-high-risk.
      Additionally, a cohort of patients with comparable baseline characteristics who
      underwent LT were similarly classified into pre-low and pre-high-risk groups and
      compared with the resected patients in terms of survival. RESULTS: Cirrhosis,
      aspartate transaminase, alpha-fetoprotein, Model for End-Stage Liver Disease
      score, number of nodules, and diameter of the largest nodule were preoperatively
      found to be significantly related to overall survival post-LR. Microvascular
      invasion and satellites were selected to reclassify prognosis in the resulting
      preoperative low-risk group into post-high risk. The converted group (post-high)
      demonstrated the same 5-year survival as the pre-high group. Patients undergoing
      LT had better survival overall than those undergoing LR, with the exception of
      pre-low LT and post-low LR (confirmed low-risk LR) who had similar outcomes.
      CONCLUSIONS: The new models were strongly predictive of patients' likelihood of
      survival after LR for HCC on liver cirrhosis. Liver transplantation offers a
      survival advantage over LR, except in low-risk groups where both modalities might
      be comparable.

PMID- 29574179
TI  - External Validation and Optimization of the French Association of
      Hepatopancreatobiliary Surgery and Transplantation's Score to Predict Severe
      Postoperative Biliary Leakage after Open or Laparoscopic Liver Resection.
AB  - BACKGROUND: Biliary leakage is a major contributor to morbidity after
      hepatectomy. A score to predict severe posthepatectomy biliary leakage (PHBL) was
      recently developed by the French Association of Hepatopancreatobiliary Surgery
      and Transplantation (ACHBT). The aim of the study was to validate and optimize
      the score on an external cohort. STUDY DESIGN: The ACHBT score uses 5 factors
      (blood loss, remnant ischemia, anatomic resection of segment 8, transection along
      right aspect of the left intersectional plane and associating liver partition and
      portal vein ligation for staged hepatectomy) to predict severe PHBL. The score
      was tested on an external cohort of patients undergoing hepatectomy without
      hepaticojejunostomy between 1994 and 2016 at a single center. Association between
      the score, pre- and intraoperative variables, and severe PHBL was assessed in an
      attempt to improve the score. RESULTS: Among 778 procedures performed (including
      679 [87.3%] laparoscopic and 260 [34.3%] major hepatectomies), 31 (4.0%) were
      complicated with severe PHBL. The ACHBT score showed good discrimination (AUROC
      [area under the receiver operating characteristic curve] 0.747, 95% CI 0.652 to
      0.841), calibration and accuracy (diagnostic odds ratio for a score >=1: 6.217
      [95% CI 2.642 to 14.627], for a score >=2: 6.059 [95% CI 2.858 to 12.846],and for
      a score >=3: 9.589 [95% CI 2.868 to 32.066]). On multivariable analysis, the
      ACHBT score was the only predictor of severe PHBL. A model combining the ACHBT
      score and conversion to open surgery was significantly more discriminating than
      the ACHBT score alone (AUROC 0.790 [95% CI 0.711 to 0.870], Delong's test p =
      0.002). CONCLUSIONS: The ACHBT score represents an externally validated tool to
      predict severe PHBL. Inclusion of conversion to open surgery as an additional
      factor to the score allowed it to improve its performance to predict severe PHBL
      after laparoscopic hepatectomy.

PMID- 29574180
TI  - Venous Thromboembolism-Related Readmission in Emergency General Surgery Patients:
      A Role for Prophylaxis on Discharge?
AB  - BACKGROUND: Patients undergoing emergency general surgery (EGS) operations
      experience high rates of venous thromboembolism (VTE). The rates at which
      thrombus formation occurs after discharge, and whether VTE prophylaxis at
      discharge might be warranted to prevent readmission, are unknown. This analysis
      aimed to determine risk factors associated with VTE formation after discharge for
      EGS operations. STUDY DESIGN: An analysis of the American College of Surgeons
      NSQIP database from 2013 and 2014 of patients undergoing 10 common EGS operations
      in an emergent fashion. Multivariable logistic regression modeling was used to
      determine factors that predicted VTE after discharge. RESULTS: A total of 130,036
      patients were included. The 30-day VTE rate was 1.30%, with 35% of all VTEs
      occurring after discharge. Of those who had VTE develop after discharge, 69.4%
      required readmission. Predictive factors for post-discharge VTE included
      prolonged length of stay (odds ratio [OR] 5.25; p < 0.001), presence of
      metastatic cancer (OR 2.23; p < 0.001), urinary tract infection (OR 1.91; p <
      0.001), and postoperative sepsis (OR 1.55; p < 0.001). Identified high-risk
      groups had a rate of readmission with thrombus 6 times greater than that of
      average-risk EGS patients. CONCLUSIONS: More than 30% of VTEs in the EGS
      population occur after discharge; of these, a vast majority require readmission.
      Select high-risk EGS subgroups might benefit from prophylactic anticoagulation at
      discharge.

PMID- 29574181
TI  - Diversity and Distribution of Free-living Ciliates from High-Arctic Kara Sea
      Sediments.
AB  - For the first time, free-living ciliates were studied in sediments from a variety
      of habitats in the Kara Sea (the Arctic Ocean). Ciliates were found in a wide
      range of environmental conditions (from the intertidal zone up to depths of 554m,
      from salinities ranging from 0 to 34psu, and from coarse sands and gravel to
      muddy sediments), with total abundances varying from 1 to 127ind/cm3. Altogether,
      114 species were identified, most of which were widely distributed and were
      previously reported from other Arctic regions. An unsaturated species
      accumulation curve and the presence of many rare species indicated that the Kara
      Sea is potentially as rich in ciliates as other regions. Fine- and medium-grained
      sands exhibited the richest and most abundant ciliate fauna, with many
      interstitial forms occurring up to depths of 200m; whereas both the coarse sands
      of the exposed intertidal beaches and the sublittoral muds were poorly inhabited
      by non-specific euryoecious species. The granulometric composition of sediments
      was suggested to be the main driver controlling the diversity and composition of
      ciliate communities, while the other factors, such as salinity, water
      productivity and depth, were of secondary importance.

PMID- 29574182
TI  - Tmem30a Plays Critical Roles in Ensuring the Survival of Hematopoietic Cells and
      Leukemia Cells in Mice.
AB  - The fundamental structure of eukaryotic cell plasma membrane is the phospholipid
      bilayer, which contains four major phospholipids. These phospholipids are
      asymmetrically distributed between the outer and inner leaflets. P4-ATPase
      flippase complexes play essential roles in ensuring this asymmetry. We found that
      conditional deletion of Tmem30a, the beta subunit of P4-ATPase flippase complex,
      caused pancytopenia in mice. Tmem30a deficiency resulted in depletion of lineage
      committed blood cells in the peripheral blood, spleen, and bone marrow. Ablation
      of Tmem30a also caused the depletion of hematopoietic stem cells (HSCs). HSC RNA
      sequencing results revealed that multiple biological processes and signal
      pathways were involved in the event, including mammalian target of rapamycin
      signaling, genes for HSC stemness, and genes responding to interferons. Our
      results also revealed that targeting Tmem30a signaling had therapeutic utility in
      BCR/ABL1-induced chronic myeloid leukemia.

PMID- 29574183
TI  - Random and oriented electrospun fibers based on a multicomponent, in situ
      clickable elastin-like recombinamer system for dermal tissue engineering.
AB  - : Herein we present a system to obtain fibers from clickable elastin-like
      recombinamers (ELRs) that crosslink in situ during the electrospinning process
      itself, with no need for any further treatment to stabilize them. These ELR-click
      fibers are completely stable under in vitro conditions. A wrinkled fiber
      morphology is obtained. In addition to a random fiber orientation, oriented
      fibers with a high degree of alignment and coherence can also be obtained by
      using a rotational electrode. The production of multicomponent fibers means that
      different functionalities, such as cell-adhesion domains (RGD peptides), can be
      incorporated into them. In a subsequent study, two main cell lines present in the
      dermis and epidermis, namely keratinocytes and fibroblasts, were cultured on top
      of the ELR-click fibers. Adhesion, proliferation, fluorescence, immunostaining
      and histology studies showed the cytocompatibility of these scaffolds, thus
      suggesting their possible use for wound dressings in skin tissue engineering
      applications. STATEMENT OF SIGNIFICANCE: For the first time stable electrospun
      bioactive fibers are obtained by the in situ mixing of two "clickable" ELR
      components previously described by Gonzalez et al (Acta Biomaterialia 2014). This
      work describes an efficient system to prepare fibrous scaffolds based on peptidic
      polymers by electrospinning without the need of crosslinking agents that could be
      harmful for cells or living tissues. These bioactive fibers support cell growth
      due to the inclusion of RGD motifs (Staubli et al. Biomaterials 2017). Finally,
      the in vitro biocompatibility of the two main cell types found in the outer
      layers of skin, fibroblasts and keratinocytes, indicates that this system is of
      great interest to prepare elastic artificial skin substitutes for wound healing
      applications.

PMID- 29574184
TI  - Engineering interfacial migration by collective tuning of adhesion anisotropy and
      stiffness.
AB  - : Interfacial migration is central to multiple processes including morphogenesis
      and wound healing. However, the sensitivity of interfacial migration to
      properties of the interfacial microenvironment has not been adequately explored.
      Here, we address this question by tracking motility of 3T3 fibroblasts at the
      interface of two hydrogels. By sandwiching cells between two adhesive gels
      (composed of methacrylated gelatin) or between an adhesive and a non-adhesive gel
      (composed of gellan), we show that cells are more motile in case of the latter.
      By tuning the bulk stiffness of the gellan gel, we then show that motility is
      tuned in a stiffness-dependent manner. Fastest motility observed in case of the
      stiffest gel was associated with increased cell height, suggestive of stiffness
      mediated cytoskeletal assembly. Inhibition of cell motility by contractile
      agonists and actin depolymerizing drugs is indicative of a mode of migration
      wherein cells combine contractile tractions exerted at their base and actin-based
      pushing forces on the top surface to propel themselves forward. Together, our
      results suggest that dorso-ventral adhesion anisotropy and stiffness can be
      collectively tuned to engineer interfacial migration. STATEMENT OF SIGNIFICANCE:
      It is increasingly understood that cells migrate in vivo through confining spaces
      which typically occur as pores in the matrix and through naturally occurring
      interfaces that exist between neighbouring ECM fibers, or between the stroma and
      the vasculature. Such interfaces are also created when treating wounds on the
      skin surface by covering the wounds with adhesives. How multiple cues impact
      interfacial migration has not been adequately addressed. By studying cell
      migratory behaviour at the interface of two hydrogel substrates, we identify
      adhesivity and stiffness as two critical factors that can be tuned to maximize
      cell migration. We foresee a potential use of this knowledge in the design of
      tissue adhesives for wound healing applications.

PMID- 29574185
TI  - Collagen fiber recruitment: A microstructural basis for the nonlinear response of
      the posterior pole of the eye to increases in intraocular pressure.
AB  - : Our goal was to quantify and characterize how the collagen fiber crimp waviness
      of the lamina cribrosa (LC) and peripapillary sclera (PPS) changes with
      intraocular pressure (IOP). Thirteen sheep (ovine) eyes were immersion and
      perfusion fixed while maintaining IOP at 0, 10, 15, 20, or 50 mmHg. Coronal optic
      nerve head (ONH) sections (30 um) were imaged with polarized light microscopy
      (PLM) and analyzed for collagen fiber orientation and waviness (SD of fiber
      orientation). In the LC, the waviness of every LC beam was measured. In the PPS,
      at least 900 collagen bundles were measured per eye. Using the waviness at 50
      mmHg IOP, we defined tissue-specific thresholds to determine the fraction of
      loaded or recruited fibers. We found that fiber waviness decreased with IOP (P <
      0.001). At every IOP, the waviness of the collagen fibers, and the fraction of
      fibers recruited in the LC were smaller or equal than those of the PPS (P <
      0.001). At 15 mmHg IOP, both LC and PPS had 3/4 recruited fibers and 1/4 left in
      reserve. The decreased waviness with IOP and associated fiber recruitment is
      experimental evidence of fiber-based nonlinear biomechanical behavior of the ONH.
      At all IOPs the PPS had an equal or larger fraction of fibers recruited than the
      LC. That both LC and PPS had the same fraction of recruited and reserve fibers at
      normal IOP suggests that this may be an optimal fraction of recruitment for
      healthy eyes. Whether this extends to human eyes remains unknown. STATEMENT OF
      SIGNIFICANCE: Collagen fibers exhibit a natural waviness or crimp that largely
      determine the nonlinear biomechanics of soft tissue. Experimental measurements of
      crimp morphology in the sheep eye, and how it changes with intraocular pressure
      (IOP), however, are exceedingly sparse. We quantified how posterior eye crimp
      changes with increasing IOP. We found that the lamina cribrosa and peripapillary
      sclera have fundamentally different crimp, and with increasing IOP, have
      different proportions of fibers that straighten, or get recruited, versus
      remaining wavy, or in reserve. Interestingly, at physiologic IOP of 15 mmHg, both
      tissues had about 3/4 fibers recruited and 1/4 fibers in reserve, indicating
      there may be an optimal fraction of fibers.

PMID- 29574186
TI  - miR-205-5p negatively regulates hepatic acetyl-CoA carboxylase beta mRNA in lipid
      metabolism of Oreochromis niloticus.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional gene
      regulators and that play vital roles controlling lipid metabolism. miR-205 is an
      important miRNA related to adipogenesis and lipid metabolism. However, little is
      known about the potential role of miR-205-5p in genetically improved farmed
      tilapia (GIFT, Oreochromis niloticus). In this study, we used miRanda software to
      search for potential miR-205-5p target genes and found a lipid-metabolism-related
      gene called acetyl-CoA carboxylase beta (ACACbeta). Quantitative real-time
      polymerase chain reaction data indicated that there may be a negative regulation
      relationship between miR-205-5p and ACACbeta gene expression under HFD rearing.
      Using luciferase reporter assays, we verified the binding site of miR-205-5p in
      the 3'-untranslated region of the ACACbeta mRNA. Furthermore, an in vivo
      functional analysis of miR-205-5p was performed by injecting GIFT juveniles with
      a miR-205-5p antagomir. Reduced levels of miR-205-5p in GIFT liver increased
      ACACbeta mRNA expression 12 h post-injection. miR-205-5p suppression also
      increased fatty acid synthase and peroxisome proliferator-activated receptor
      alpha mRNA levels 48 h and 120 h post-injection, respectively. Taken together,
      our results indicate that miR-205-5p negative regulates hepatic ACACbeta mRNA
      expression, and may serve as an important regulator in controlling hepatic lipid
      metabolism in GIFT.

PMID- 29574187
TI  - The analyses of relationships among nucleotide, synonymous codon and amino acid
      usages for E2 gene of bovine viral diarrhea virus.
AB  - In this study, the systemic analyses of nucleotide, codon and amino acid usages
      for E2 gene of bovine viral diarrhea virus (BVDV) were carried out for estimating
      its genetic features. The nucleotide usage pattern at the first codon position
      was strongly influenced by the overall nucleotide composition, while the
      nucleotide usage patterns at the second and third codon positions seemed to have
      little link to the overall nucleotide composition. The result indicated that the
      mutation pressure from nucleotide composition constraint was not the single
      evolutionary force for genetic features of BVDV E2 gene. Just 18 out of 59
      synonymous codons were similar with synonymous codon usage patterns for E2 gene
      between BVDV1 and BVDV2, while all synonymous codons which contain CpG
      dinucleotides were selected at the low level by E2 gene, suggesting that this
      gene suppressed the usages of codons containing CpG dinucleotides to regulate E2
      gene replicate and transcript efficiently and avoid immune response from infected
      hosts. Amino acid usage patterns of E2 protein were generally different between
      BVDV1 and BVDV2. The patterns of synonymous codon and amino acid usages for E2
      gene might be caused by the equilibrium of evolutionary forces from virus and
      host. Our work gave new investigations into the role of host origin in the
      formations of synonymous codon/amino acid usages and the evolutionary trend of
      BVDV E2 gene. The genetic characteristics that codon/amino acid usages of E2 gene
      adapted to the internal environment of individual animals might assist in
      understanding the changes of genetics and antigenicity for newly emerging BVDV.

PMID- 29574188
TI  - New bifunctional restriction-modification enzyme AloI isoschizomer (PcoI):
      Bioinformatics analysis, purification and activity confirmation.
AB  - Type II restriction endonucleases and modification DNA-methyltransferases are key
      instruments of genetic engineering. Recently the number of proteins assigned to
      this group exceeds 8500. Subtype IIC organizes bifunctional endonuclease
      methyltransferase enzymes and currently consists of 16 described members. Here we
      present phylogenetic tree of 22 new potential bifunctional endonucleases. The
      majority of them are thought to be fusions of a restriction nuclease with a DNA
      methyltransferase and a target recognition subunit of type I restriction
      modification systems (R-M-S structure). A RM.AloI isoschizomer from Prevotella
      copri DSM-18205, PcoI, has been cloned, purified and its REase activity
      demonstrated. It cuts DNA in magnesium-dependent manner and demonstrates high
      affinity to DNA, which probably reflects its mechanism of action. This work
      provides additional proves that gene fusion might play an important role in
      evolution of restriction-modification systems and other DNA-modifying proteins.

PMID- 29574189
TI  - Comparative antennal transcriptome of Apis cerana cerana from four developmental
      stages.
AB  - Apis cerana cerana, an important endemic honey bee species in China, possesses
      valuable characteristics such as a sensitive olfactory system, good foraging
      ability, and strong resistance to parasitic mites. Here, we performed
      transcriptome sequencing of the antenna, the major chemosensory organ of the bee,
      using an Illumina sequencer, to identify typical differentially expressed genes
      (DEGs) in adult worker bees of different ages, namely, T1 (1 day); T2 (10 days);
      T3 (15 days); and T4 (25 days). Surprisingly, the expression levels of DEGs
      changed significantly between the T1 period and the other three periods. All the
      DEGs were classified into 26 expression profiles by trend analysis. Selected
      trend clusters were analyzed, and valuable information on gene expression
      patterns was obtained. We found that the expression levels of genes encoding
      cuticle proteins declined after eclosion, while those of immunity-related genes
      increased. In addition, genes encoding venom proteins and major royal jelly
      proteins were enriched at the T2 stage; small heat shock proteins showed
      significantly higher expression at the T3 stage; and some metabolism-related
      genes were more highly expressed at the T4 stage. The DEGs identified in this
      study may serve as a valuable resource for the characterization of expression
      patterns of antennal genes in A. cerana cerana. Furthermore, this study provides
      insights into the relationship between labor division in social bees and gene
      function.

PMID- 29574190
TI  - The transcriptome analyses of Tagetes erecta provides novel insights into
      secondary metabolite biosynthesis during flower development.
AB  - Genomic and transcriptomic sequences of Tagetes erecta are very limited in public
      databases, despite its nutritional and economical value. In this study, nine cDNA
      libraries were constructed from leaves, immature and mature flowers and sequenced
      using Illumina Hiseq 2000. Over 45.66 Gb nucleotides were generated and a total
      of 72,499 unigenes were assembled, 34,892 (48.13%) of which were annotated in NR,
      Swiss-prot, COG, GO, KOG, KEGG and Pfam. 11,721 differentially expressed genes
      were identified in leaves, immature flowers and mature flowers. The
      differentially expressed genes between immature flowers and mature flowers were
      mainly involved in photosynthesis and secondary metabolite biosynthesis.
      Additionally, the catalysis-related unigenes and their expression involved in
      carotenoids biosynthesis were determined. Using our newly identified reference
      genes as internal control, the expression profiles of carotenoids biosynthetic
      genes were verified by real-time qRT-PCR, and four of the unigenes were cloned
      for full length sequences confirmation. Furthermore, gene expansions occurred
      among the catalytic gene families in carotenoids biosynthesis pathway, which
      might explain the high pigment content in T. erecta.

PMID- 29574191
TI  - The acroframosome-acroplaxome-manchette axis may function in sperm head shaping
      and male fertility.
AB  - Sperm malformation is one of the main reasons for male infertility, but the
      precise mechanisms of this process remain undiscovered. The major process of
      spermiogenesis is sperm head shaping. Cytoskeleton is a crucial unit in this
      process, as the acroplaxome and manchette are two kinds of momentous structures
      cooperated with various functional proteins to insure the formation of acrosome
      and nucleus. One is primarily formed by filamentous actin (F-actin) and
      responsible for transverse acrosome extension and concentration, another plays as
      the mainstay of nuclear deformation through circular arrangement of microtubules
      (MTs). We suspect that the acroplaxome alone cannot maintain such a spatial
      framework of the acrosome. Previous studies have also revealed that a nucleus
      without acrosome could not induce the formation of ectoplasmic specialization. In
      this review, we integrated most of the key proteins that have been proven to
      participate in the essential developmental steps of post-meiosis. We also propose
      that the ambient MTs of the acrosome might be emanated from the Golgi apparatus.
      They form a novel cytoskeleton termed acroframosome (AFS) to transport vesicles
      and proteins during acrosome biogenesis. The hypothesis of the acroframosome
      acroplaxome-manchette (AAM) cytoskeletal system is likely to be the axis of head
      to-tail spermiogenesis.

PMID- 29574192
TI  - Comprehensive analysis of differentially expressed genes reveals the molecular
      response to elevated CO2 levels in two sea buckthorn cultivars.
AB  - Atmospheric carbon dioxide (CO2) concentration increases every year. It is
      critical to understand the elevated CO2 response molecular mechanisms of plants
      using genomic techniques. Hippophae rhamnoides L. is a high stress resistance
      plant species widely distributed in Europe and Asia. However, the molecular
      mechanism of elevated CO2 response in H. rhamnoides has been limited. In this
      study, transcriptomic analysis of two sea buckthorn cultivars under different CO2
      concentrations was performed, based on the next-generation illumina sequencing
      platform and de novo assembly. We identified 4740 differentially expressed genes
      in sea buckthorn response to elevated CO2 concentrations. According to the gene
      ontology (GO) results, photosystem I, photosynthesis and chloroplast thylakoid
      membrane were the main enriched terms in 'xiangyang' sea buckthorn. In 'zhongguo'
      sea buckthorn, photosynthesis was also the main significantly enriched term.
      However, the number of photosynthesis related differentially expressed genes were
      different between two sea buckthorn cultivars. Our GO and pathway analyses
      indicated that the expression levels of the transcription factors WRKY, MYB and
      NAC were significantly different between the two sea buckthorn cultivars. This
      study provides a reliable transcriptome sequence resource and is a valuable
      resource for genetic and genomic researches for plants under high CO2
      concentration in the future.

PMID- 29574193
TI  - Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab.
AB  - Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular
      endothelial growth factor (VEGF), is approved for treatment of metastatic
      colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney
      cancer, and glioblastoma. To support clinical development of the potential
      bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural,
      functional, toxicological, and toxicokinetic similarity to bevacizumab sourced
      from the European Union (bevacizumab-EU) and United States (bevacizumab-US).
      Peptide mapping demonstrated the amino acid sequence of PF-06439535 was identical
      to bevacizumab-EU and bevacizumab-US. Biologic activity, measured via inhibition
      of VEGF-induced cell proliferation in human umbilical vein endothelial cells and
      binding to VEGF isoforms, was similar across the three drugs. In vivo similarity
      was demonstrated in cynomolgus monkeys administered intravenous PF-06439535 or
      bevacizumab-EU (0 or 10 mg/kg/dose twice weekly for 1 month; total of nine
      doses). Systemic exposure appeared similar and test article-related effects were
      limited to physeal dysplasia of the distal femur. The potential for non-target
      mediated toxicity of PF-06439535 was evaluated in rats administered intravenous
      PF-06439535 (15 or 150 mg/kg/dose twice weekly for 15 days; total of five doses).
      Nonadverse higher liver weights and minimal sinusoidal cell hyperplasia were
      observed. Collectively, these studies demonstrated similarity of PF-06439535 to
      bevacizumab, supporting entry into clinical development.

PMID- 29574194
TI  - Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of
      new criterion for toxicity determination to test article-induced changes.
AB  - G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated
      from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have
      immunotoxicity, the need to ensure safety for long-term administration has been
      raised. In this study, a 90-day repeated oral dose toxicity test was performed in
      rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A
      toxicity determination criterion based on the significant change caused by the
      administration of the substancewas developed for estimating NOEL, NOAEL and
      LOAELapplied to this study. When analyzing the immunological markers, no
      significant changes were observed, even if other significant changes were
      observed in the high dose group. In accordance with the toxicity determination
      criterion developed, the NOEL in male and female has been determined as 2500
      mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The
      toxicity determination criterion, applied for the first time in the repeated dose
      toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more
      clearly; nevertheless, the toxicity determination criterion needs to be
      supplemented by adding differentiating adverse effects and non-adverse effects
      based on more experiences of the repeated dose toxicity tests.

PMID- 29574196
TI  - Imaging and Laparoscopic Findings in a Patient with Congenital Uterine
      Arteriovenous Malformation.

PMID- 29574197
TI  - Working memory training mostly engages general-purpose large-scale networks for
      learning.
AB  - The present meta-analytic study examined brain activation changes following
      working memory (WM) training, a form of cognitive training that has attracted
      considerable interest. Comparisons with perceptual-motor (PM) learning revealed
      that WM training engages domain-general large-scale networks for learning
      encompassing the dorsal attention and salience networks, sensory areas, and
      striatum. Also the dynamics of the training-induced brain activation changes
      within these networks showed a high overlap between WM and PM training. The
      distinguishing feature for WM training was the consistent modulation of the dorso
      and ventrolateral prefrontal cortex (DLPFC/VLPFC) activity. The strongest
      candidate for mediating transfer to similar untrained WM tasks was the
      frontostriatal system, showing higher striatal and VLPFC activations, and lower
      DLPFC activations after training. Modulation of transfer-related areas occurred
      mostly with longer training periods. Overall, our findings place WM training
      effects into a general perception-action cycle, where some modulations may depend
      on the specific cognitive demands of a training task.

PMID- 29574195
TI  - Characterizing risk assessments for the development of occupational exposure
      limits for engineered nanomaterials.
AB  - The commercialization of engineered nanomaterials (ENMs) began in the early
      2000's. Since then the number of commercial products and the number of workers
      potentially exposed to ENMs is growing, as is the need to evaluate and manage the
      potential health risks. Occupational exposure limits (OELs) have been developed
      for some of the first generation of ENMs. These OELs have been based on risk
      assessments that progressed from qualitative to quantitative as nanotoxicology
      data became available. In this paper, that progression is characterized. It
      traces OEL development through the qualitative approach of general groups of ENMs
      based primarily on read-across with other materials to quantitative risk
      assessments for nanoscale particles including titanium dioxide, carbon nanotubes
      and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent
      prototypic approaches to risk assessment and OEL development for ENMs. Such
      substance-by-substance efforts are not practical given the insufficient data for
      many ENMs that are currently being used or potentially entering commerce.
      Consequently, categorical approaches are emerging to group and rank ENMs by
      hazard and potential health risk. The strengths and limitations of these
      approaches are described, and future derivations and research needs are
      discussed. Critical needs in moving forward with understanding the health effects
      of the numerous EMNs include more standardized and accessible quantitative data
      on the toxicity and physicochemical properties of ENMs.

PMID- 29574198
TI  - Pilot-scale evaluation of micropollutant abatements by conventional ozonation,
      UV/O3, and an electro-peroxone process.
AB  - The electro-peroxone (E-peroxone) process is an emerging ozone-based advanced
      oxidation process (AOP) that has shown large potential for micropollutant
      abatement in water treatment. To evaluate its performance under more realistic
      conditions of water treatment, a continuous-flow pilot E-peroxone system was
      developed and compared with conventional ozonation and a UV/O3 process for
      micropollutant abatements in various water matrices (groundwater, surface water,
      and secondary wastewater effluent) in this study. With a specific ozone dose of
      1.5 mg O3/mg DOC, micropollutants that have high and moderate reactivity with
      ozone (O3) (diclofenac, naproxen, gemfibrozil, and bezafibrate) could be
      sufficiently abated (>90% abatement) in the various waters by all three
      processes. However, ozone-resistant micropollutants (ibuprofen, clofibric acid,
      and chloramphenicol) were abated only by ~32-68%, 68-91%, and 73-90% during
      conventional ozonation of the selected groundwater, surface water, and secondary
      wastewater effluent, respectively. By electro-generating H2O2 or applying UV
      irradiation to enhance O3 transformation to *OH during ozonation, the E-peroxone
      and UV/O3 processes similarly enhanced the abatement efficiencies of ozone
      resistant micropollutants by ~15-43%, ~5-15%, and ~5-10% in the groundwater,
      surface water, and secondary wastewater effluent, respectively. In addition, the
      E-peroxone and UV/O3 processes significantly reduced bromate formation during the
      treatment of the three waters compared to conventional ozonation. Due to its
      higher efficiency, the E-peroxone process reduced ~10-53% of the energy
      consumption required to abate the concentration of chloramphenicol (the most
      ozone-resistant micropollutant spiked in the waters) by 1 order of magnitude in
      the three waters compared to conventional ozonation. In contrast, the UV/O3
      process consumed approximately 4-10 times higher energy than conventional
      ozonation. This pilot-scale study demonstrates that the E-peroxone process can
      provide a feasible, effective, and energy-efficient alternative for
      micropollutant abatement and bromate control in water and wastewater treatment.

PMID- 29574199
TI  - Successful aerobic bioremediation of groundwater contaminated with higher
      chlorinated phenols by indigenous degrader bacteria.
AB  - The xenobiotic priority pollutant pentachlorophenol has been used as a timber
      preservative in a polychlorophenol bulk synthesis product containing also
      tetrachlorophenol and trichlorophenol. Highly soluble chlorophenol salts have
      leaked into groundwater, causing severe contamination of large aquifers. Natural
      attenuation of higher-chlorinated phenols (HCPs: pentachlorophenol +
      tetrachlorophenol) at historically polluted sites has been inefficient, but a 4
      year full scale in situ biostimulation of a chlorophenol-contaminated aquifer by
      circulation and re-infiltration of aerated groundwater was remarkably successful:
      pentachlorophenol decreased from 400 MUg L-1 to <1 MUg L-1 and tetrachlorophenols
      from 4000 MUg L-1 to <10 MUg L-1. The pcpB gene, the gene encoding
      pentachlorophenol hydroxylase - the first and rate-limiting enzyme in the only
      fully characterised aerobic HCP degradation pathway - was present in up to 10% of
      the indigenous bacteria already 4 months after the start of aeration. The novel
      quantitative PCR assay detected the pcpB gene in situ also in the chlorophenol
      plume of another historically polluted aquifer with no remediation history.
      Hotspot groundwater HCPs from this site were degraded efficiently during a 3-week
      microcosm incubation with one-time aeration but no other additives: from 5400 MUg
      L-1 to 1200 MUg L-1 and to 200 MUg L-1 in lightly and fully aerated microcosms,
      respectively, coupled with up to 2400% enrichment of the pcpB gene. Accumulation
      of lower-chlorinated metabolites was observed in neither in situ remediation nor
      microcosms, supporting the assumption that HCP removal was due to the aerobic
      degradation pathway where the first step limits the mineralisation rate. Our
      results demonstrate that bacteria capable of aerobic mineralisation of xenobiotic
      pentachlorophenol and tetrachlorophenol can be present at long-term polluted
      groundwater sites, making bioremediation by simple aeration a viable and
      economically attractive alternative.

PMID- 29574200
TI  - Effective phosphate removal for advanced water treatment using low energy,
      migration electric-field assisted electrocoagulation.
AB  - A migration electric-field assisted electrocoagulation (MEAEC) system was
      developed to increase phosphate removal from domestic wastewater, with reduced
      energy consumption, using a titanium charging (inert) electrode and a sacrificial
      iron anode. In the MEAEC, an electric field was applied between the inert
      electrode (titanium) and an air cathode to drive migration of phosphate anions
      towards the sacrificial anode. Current was then applied between the sacrificial
      anode (Fe or Al mesh) and the air cathode to drive electrocoagulation of
      phosphate. A MEAEC with the Fe electrode using primary clarifier effluent
      achieved 98% phosphate removal, producing water with a total phosphorus of 0.3
      mg/L with <6 min total treatment time (five cycles; each 10 s inert electrode
      charging, and 1 min electrocoagulation), at a constant current density of 1
      mA/cm2. In the absence of the 10 s charging time, electrocoagulation required 15
      min for the same removal. With an aluminum anode and the same phosphorus removal,
      the MEAEC required 7 cycles (7 min total treatment, 1 min 10 s total charging),
      while conventional electrocoagulation required 20 min. The energy demand of Fe
      MEAEC was only 0.039 kWh/m3 for 98% phosphate removal, which was 35% less than
      with the Al-MEAEC of 0.06 kWh/m3, and 28% less than that previously obtained
      using an inert graphite electrode. Analysis of the precipitate showed that a less
      porous precipitate was obtained with the Al anode than with the Fe anode. The
      phosphorus in precipitate of Fe-MEAEC was identified as PO43- and HPO42-, while
      the Fe was present as both Fe2+ and Fe3+. Only HPO42- and Al3+ were identified in
      the precipitate of the Al-MEAEC. These results indicated that the MEAEC with a
      titanium inert charging electrode and iron anode could achieve the most efficient
      phosphate removal with very low energy demands, compared to previous
      electrochemical approaches.

PMID- 29574201
TI  - Enhanced pharmaceutical removal from water in a three step bio-ozone-bio process.
AB  - Individual treatment processes like biological treatment or ozonation have their
      limitations for the removal of pharmaceuticals from secondary clarified effluents
      with high organic matter concentrations (i.e. 17 mg TOC/L). These limitations can
      be overcome by combining these two processes for a cost-effective pharmaceutical
      removal. A three-step biological-ozone-biological (BO3B) treatment process was
      therefore designed for the enhanced pharmaceutical removal from wastewater
      effluent. The first biological step removed 38% of ozone scavenging TOC, thus
      proportionally reducing the absolute ozone input for the subsequent ozonation.
      Complementariness between biological and ozone treatment, i.e. targeting
      different pharmaceuticals, resulted in cost-effective pharmaceutical removal by
      the overall BO3B process. At a low ozone dose of 0.2 g O3/g TOC and an HRT of
      1.46 h in the biological reactors, the removal of 8 out of 9 pharmaceuticals
      exceeded 85%, except for metoprolol (60%). Testing various ozone doses and HRTs
      revealed that pharmaceuticals were ineffectively removed at 0.1 g O3/g TOC and an
      HRT of 0.3 h. At HRTs of 0.47 and 1.46 h easily and moderately biodegradable
      pharmaceuticals such as caffeine, gemfibrozil, ibuprofen, naproxen and
      sulfamethoxazole were over 95% removed by biological treatment. The
      biorecalcitrant carbamazepine was completely ozonated at a dose of 0.4 g O3/g
      TOC. Ozonation products are likely biodegraded in the last biological reactor as
      a 17% TOC removal was found. No appreciable acute toxicity towards D. magna, P.
      subcapitata and V. fischeri was found after exposure to the influents and
      effluents of the individual BO3B reactors. The BO3B process is estimated to
      increase the yearly wastewater treatment tariff per population equivalent in the
      Netherlands by less than 10%. Overall, the BO3B process is a cost-effective
      treatment process for the removal of pharmaceuticals from secondary clarified
      effluents.

PMID- 29574202
TI  - Structure-based design of bacterial transglycosylase inhibitors incorporating
      biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties.
AB  - Transglycosylase (TGase) is essential to biosynthesis of peptidoglycan for
      formation of bacterial cell wall. Moenomycin is a potent TGase inhibitor, but not
      used in clinic treatment due to its poor pharmacokinetics. The E-F disaccharide,
      phosphoglycerate and lipid tail in moenomycin are crucial elements for TGase
      inhibition and antibacterial activity. Based on this scaffold, a series of
      truncated mimics comprising biphenyl, amine linker and 2-alkoxy-3
      phosphorylpropanoate moieties were designed to test their TGase inhibitory
      activity. In this design, the phosphorylpropanoate group is a surrogate of
      phosphoglycerate with improved stability. A library of lipid tails can be
      constructed by a straightforward approach using Cu(I)-catalyzed (3 + 2)
      cycloaddition reactions, and the as-synthesized triazole ring can provide
      additional hydrogen bonds in the TGase active site. Our molecular docking
      experiments reveal that the biphenyl group provides pi-pi and pi-cation
      interactions to act as a simplified alternative of the C-E disaccharide in
      moenomycin. To play the role of the oxonium transition state in
      transglycosylation, the amine linker exists as a positively charged species in
      physiological condition to attain electrostatic interactions with acidic
      residues. In this study, two biphenyl-linked 2-alkoxy-3-phosphorylpropanoate
      compounds (8 and 10) are found to exhibit modest inhibitory activity (IC50 ~ 150
      MUM) against the TGase of Acinetobacter baumannii and good antibacterial activity
      against Staphylococcus aureus (MIC = 6.3 MUM).

PMID- 29574203
TI  - Inhibitors of phosphodiesterase as cancer therapeutics.
AB  - Phosphodiesterases (PDEs) are a class of enzymes that hydrolyze cyclic adenosine
      monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which is involved
      in many physiological processes including visual transduction, cell proliferation
      and differentiation, cell-cycle regulation, gene expression, inflammation,
      apoptosis, and metabolic function. PDEs are composed of 11 different families and
      each family contains different subtypes. The distribution, expression, regulation
      mode and sensitivity to inhibitors of each subtype are different, and they are
      involved in cancer, inflammation, asthma, depression, erectile dysfunction and
      other pathological processes of development. A large number of studies have shown
      that PDEs play an important role in the development of tumors by affecting the
      intracellular level of cAMP and/or cGMP and PDEs could become diagnostic markers
      or therapeutic targets. This review will give a brief overview of the expression
      and regulation of PDE families in the process of tumorigenesis and their anti
      tumor inhibitors, which may guide the design of novel therapeutic drugs targeting
      PDEs for anticancer agent.

PMID- 29574204
TI  - Design and synthesis of aryloxypropanolamine as beta3-adrenergic receptor
      antagonist in cancer and lipolysis.
AB  - beta-adrenergic receptors (beta-ARs) are broadly distributed in various tissues
      and regulate a panel of important physiological functions and disease states
      including cancer. Above all, beta3-adrenergic receptor (beta3-AR) plays a
      significant role in regulating lipolysis and thermogenesis in adipose tissue. In
      this study, we designed and synthesized a series of novel L-748,337 derivatives
      as selective human beta3-AR antagonists. Among all the tested L-748,337 analogs,
      compound 23d was found to display 23-fold more potent beta3-AR antagonist
      activity (EC50 = 0.5117 nM) than L-748,337 (EC50 = 11.91 nM). In vivo, compound
      23d could alleviate weight loss and inhibit tumor growth in C26 tumor cachexia
      animal model.

PMID- 29574205
TI  - DSM-flux: A new technology for reliable Combined Sewer Overflow discharge
      monitoring with low uncertainties.
AB  - In the past ten years, governments from the European Union have been encouraged
      to collect volume and quality data for all the effluent overflows from separated
      stormwater and combined sewer systems that result in a significant environmental
      impact on receiving water bodies. Methods to monitor and control these flows
      require improvements, particularly for complex Combined Sewer Overflow (CSO)
      structures. The DSM-flux (Device for Stormwater and combined sewer flows
      Monitoring and the control of pollutant fluxes) is a new pre-designed and pre
      calibrated channel that provides appropriate hydraulic conditions suitable for
      measurement of overflow rates and volumes by means of one water level gauge. In
      this paper, a stage-discharge relation for the DSM-flux is obtained
      experimentally and validated for multiple inflow hydraulic configurations.
      Uncertainties in CSO discharges and volumes are estimated within the Guide to the
      expression of Uncertainty in Measurement (GUM) framework. Whatever the upstream
      hydraulic conditions are, relative uncertainties are lower than 15% and 2% for
      the investigated discharges and volumes, respectively.

PMID- 29574206
TI  - Full-scale effects of addition of sludge from water treatment stations into
      processes of sewage treatment by conventional activated sludge.
AB  - An emerging practice for water treatment plant (WTP) sludge is its disposal in
      wastewater treatment plants (WWTP), an alternative that does not require the
      installation of sludge treatment facilities in the WTP. This practice can cause
      both positive and negative impacts in the WWTP processes since the WTP sludge
      does not have the same characteristics as domestic wastewater. This issue gives
      plenty of information in laboratory and pilot scales, but lacks data from full
      scale studies. The main purpose of this paper is to study the impact of disposing
      sludge from the Rio Grande conventional WTP into the ABC WWTP, an activated
      sludge process facility. Both plants are located in Sao Paulo, Brazil, and are
      full-scale facilities. The WTP volumetric flow rate (4.5 m3/s) is almost three
      times that of WWTP (1.6 m3/s). The data used in this study came from monitoring
      the processes at both plants. The WWTP liquid phase treatment analysis included
      the variables BOD, COD, TSS, VSS, ammonia, total nitrogen, phosphorus and iron,
      measured at the inlet, primary effluent, mixed liquor, and effluent. For the WWTP
      solids treatment, the parameters tested were total and volatile solids. The
      performance of the WWTP process was analyzed with and without sludge addition:
      'without sludge' in years 2005 and 2006 and 'with sludge' from January 2007 to
      March 2008. During the second period, the WTP sludge addition increased the WWTP
      removal efficiencies for solids (93%-96%), organic matter (92%-94% for BOD) and
      phosphorus (52%-88%), when compared to the period 'without sludge'. These
      improvements can be explained by higher feed concentrations combined to same or
      lower effluent concentrations in the 'with sludge' period. No critical negative
      impacts occurred in the sludge treatment facilities, since the treatment units
      absorbed the extra solids load from the WTP sludge.

PMID- 29574207
TI  - Making the best use of experts' estimates to prioritise monitoring and management
      actions: A freshwater case study.
AB  - Under limited time and resources, ecological managers are under increasing
      pressure to demonstrate tangible impact of monitoring activities. Value of
      Information (VOI) has been advocated as an ideal tool to evaluate whether more
      data is required to improve expected management outcomes. Yet, despite several
      recent works explaining its value, VOI remains seldom used in practice. Here we
      provide an example of a successful ecological application of VOI. We apply VOI to
      a novel multi-objective freshwater management problem and show how to make the
      best use of expert data through a robust sensitivity analysis. Unlike previous
      VOI approaches, our analysis provides statistical confidence to our
      recommendations. We apply our approach to the recovery of Moira grass
      (Pseudoraphis spinescens) plains, a threatened vegetation community at the Ramsar
      listed Barmah Forest on the Murray River, Australia. Working closely with
      managers, we discovered that although many threats may impede Moira grass
      recovery, reducing grazing pressure and applying ideal depth and duration of
      flooding were most likely to lead to recovery. We found that learning from
      monitoring can significantly increase the existing extent of Moira grass,
      although these gains are modest compared to immediate management action. Our
      study shows how VOI can be used to demonstrate efficient use of limited
      environmental water to maximise ecological impact and increase transparency when
      making monitoring or management decisions. More broadly, the study methods will
      be of interest to any environmental manager who needs to prioritise monitoring
      and evaluation activities subject to a limited research budget. At a time where
      researchers and managers are asked to be more accountable for their decision
      making, VOI provides a very accessible tool that can speed up the decision of
      whether to wait and collect more data or act immediately despite uncertainty.

PMID- 29574208
TI  - An optimization model for carbon capture & storage/utilization vs. carbon
      trading: A case study of fossil-fired power plants in Turkey.
AB  - We consider fossil-fired power plants that operate in an environment where a cap
      and trade system is in operation. These plants need to choose between carbon
      capture and storage (CCS), carbon capture and utilization (CCU), or carbon
      trading in order to obey emissions limits enforced by the government. We develop
      a mixed-integer programming model that decides on the capacities of carbon
      capture units, if it is optimal to install them, the transportation network that
      needs to be built for transporting the carbon captured, and the locations of
      storage sites, if they are decided to be built. Main restrictions on the system
      are the minimum and maximum capacities of the different parts of the pipeline
      network, the amount of carbon that can be sold to companies for utilization, and
      the capacities on the storage sites. Under these restrictions, the model aims to
      minimize the net present value of the sum of the costs associated with
      installation and operation of the carbon capture unit and the transportation of
      carbon, the storage cost in case of CCS, the cost (or revenue) that results from
      the emissions trading system, and finally the negative revenue of selling the
      carbon to other entities for utilization. We implement the model on General
      Algebraic Modeling System (GAMS) by using data associated with two coal-fired
      power plants located in different regions of Turkey. We choose enhanced oil
      recovery (EOR) as the process in which carbon would be utilized. The results show
      that CCU is preferable to CCS as long as there is sufficient demand in the EOR
      market. The distance between the location of emission and location of
      utilization/storage, and the capacity limits on the pipes are an important factor
      in deciding between carbon capture and carbon trading. At carbon prices over
      $15/ton, carbon capture becomes preferable to carbon trading. These results show
      that as far as Turkey is concerned, CCU should be prioritized as a means of
      reducing nation-wide carbon emissions in an environmentally and economically
      rewarding manner. The model developed in this study is generic, and it can be
      applied to any industry at any location, as long as the required inputs are
      available.

PMID- 29574209
TI  - Degradation of Penicillin G by heat activated persulfate in aqueous solution.
AB  - We used Heat Activated of Persulfate (HAP) to decompose Penicillin G (PEN G) in
      aqueous solution. The effect of pH (3-11), temperature (313-353 K), and initial
      concentration of Sodium Persulfate (SPS) (0.05-0.5 mM) on the decomposition level
      of PEN G were investigated. The residue of PEN G was determined by
      spectrophotometry at the wavelength of 290 nm. Also, the Chemical Oxygen Demand
      (COD) was measured in each experiment. The Total Organic Carbon (TOC) analysis
      was utilized for surveying the mineralization of PEN G. In addition, based on
      Arrhenius equation, the activation energy of PEN G decomposition was calculated.
      The results indicated that the maximum PEN G removal rate was obtained at pH 5
      and by increasing the doses of SPS from 0.05 to 0.5 mM, the PEN G decomposition
      was enhanced. It was found that an increase in temperature is accompanied by an
      increase in removal efficiency of PEN G. The activation energy of the studied
      process was determined to be 94.8 kJ mol-1, suggesting that a moderate activation
      energy is required for PEN G decomposition. The TOC measurements indicate that
      the HAP can efficiently mineralize PEN G. Besides, the presence of the scavengers
      significantly suppressed the HAP process to remove the PEN G. Overall, the
      results of this study demonstrate that using HAP process can be a suitable method
      for decomposing of PEN G in aqueous solutions.

PMID- 29574210
TI  - TAT-mediated intracellular delivery of carboxypeptidase G2 protects against
      methotrexate-induced cell death in HepG2 cells.
AB  - Side effects of methotrexate (MTX) especially hepatotoxicity limits clinical
      applications of this anticancer agent. Carboxypeptidase G2 (CPG2) is
      administrated for the treatment of elevated plasma concentrations of MTX. In this
      study, we have investigated the intracellular delivery of CPG2 fused to the
      transactivator transduction domain (TAT) and its protective effects against MTX
      induced cell death of HepG2 cells. We have observed that both native and
      denatured forms of the enzyme transduced into the HepG2 cells efficiently in a
      concentration and time-dependent manner. The denatured protein transduced with
      higher efficiency than the native form and was functional inside the cells. MTX
      exposure significantly decreased HepG2 cell viability in a dose- and time
      dependent manner. The cell viability after 24 and 48 h of incubation with 100 MUM
      MTX was reduced to 44.37% and 17.69%, respectively. In cells pretreated with
      native and denatured TAT-CPG2 protein the cell viability was 98.63% and 86.31%
      after 24 and 48 h, respectively. Treatment with MTX increased the number of
      apoptotic HepG2 cells to 90.23% after 48 h. However, the apoptosis percentage in
      cells pretreated with native and denatured TAT-CPG2 was 21.49% and 22.28%,
      respectively. Our results showed that TAT-CPG2 significantly prevents MTX-induced
      oxidative stress by decreasing the formation of ROS and increasing the content of
      glutathione (GSH) and catalase activity. Our finding indicates that both native
      and denatured TAT-CPG2 strongly protect HepG2 cells against MTX-induced oxidative
      stress and apoptosis. Hence, intracellular delivery of CPG2 might provide a new
      therapeutic strategy for protecting against MTX mediated cytotoxicity.

PMID- 29574211
TI  - EU decision-making for marketing authorization of advanced therapy medicinal
      products: a case study.
AB  - A comparative analysis of assessment procedures for authorization of all European
      Union (EU) applications for advanced therapy medicinal products (ATMPs) shows
      that negative opinions were associated with a lack of clinical efficacy and
      identified severe safety risks. Unmet medical need was often considered in
      positive opinions and outweighed scientific uncertainties. Numerous quality
      issues illustrate the difficulties in this domain for ATMP development.
      Altogether, it suggests that setting appropriate standards for ATMP authorization
      in Europe, similar to elsewhere, is a learning experience. The experimental
      characteristics of authorized ATMPs urge regulators, industry, and clinical
      practice to pay accurate attention to post-marketing risk management to limit
      patient risk. Methodologies for ATMP development and regulatory evaluations need
      to be continuously evaluated for the field to flourish.

PMID- 29574212
TI  - Computational modeling approaches to quantitative structure-binding kinetics
      relationships in drug discovery.
AB  - Simple comparative correlation analyses and quantitative structure-kinetics
      relationship (QSKR) models highlight the interplay of kinetic rates and binding
      affinity as an essential feature in drug design and discovery. The choice of the
      molecular series, and their structural variations, used in QSKR modeling is
      fundamental to understanding the mechanistic implications of ligand and/or drug
      target binding and/or unbinding processes. Here, we discuss the implications of
      linear correlations between kinetic rates and binding affinity constants and the
      relevance of the computational approaches to QSKR modeling.

PMID- 29574213
TI  - Strategic R&D transactions in personalized drug development.
AB  - Although external collaboration capability influences the development of
      personalized medicine, key transactions in the pharmaceutical industry have not
      been addressed. To explore specific trends in interorganizational transactions
      and key players, we longitudinally surveyed strategic transactions, comparing
      them with other advanced medical developments, such as antibody therapy, as
      controls. We found that the financing deals of start-ups have surged over the
      past decade, accelerating intellectual property (IP) creation. Our correlation
      and regression analyses identified determinants of financing deals among alliance
      deals, acquisition deals, patents, research and development (R&D) licenses,
      market licenses, and scientific papers. They showed that patents positively
      correlated with transactions, and that the number of R&D licenses significantly
      predicted financing deals. This indicates, for the first time, that start-ups and
      investors lead progress in personalized medicine.

PMID- 29574214
TI  - Mechanistic insights into functional characteristics of native crotamine.
AB  - The chemical composition of snake venoms is a complex mixture of proteins and
      peptides that can be pharmacologically active. Crotamine, a cell-penetrating
      peptide, has been described to have antimicrobial properties and it exerts its
      effects by interacting selectively with different structures, inducing changes in
      the ion flow pattern and cellular responses. However, its real therapeutic
      potential is not yet fully known. Bearing in mind that crotamine is a promising
      molecule in therapeutics, this study investigated the action of purified molecule
      in three aspects: I) antibacterial action on different species of clinical
      interest, II) the effect of two different concentrations of the molecule on
      platelet aggregation, and III) its effects on isolated mitochondria. Crotamine
      was purified to homogeneity in a single step procedure using Heparin Sepharose.
      The molecular mass of the purified enzyme was 4881.4 Da, as determined by mass
      spectrometry. To assess antibacterial action, changes in the parameters of
      bacterial oxidative stress were determined. The peptide showed antibacterial
      activity on Escherichia coli (MIC: 2.0 MUg/MUL), Staphylococcus aureus (MIC: 8-16
      MUg/MUL) and methicillin-resistant Staphylococcus aureus (MIC: 4.0-8.0 MUg/MUL),
      inducing bacterial death by lipid peroxidation and oxidation of target proteins,
      determined by thiobarbituric acid reactive substances and sulfhydryl groups,
      respectively. Crotamine induced increased platelet aggregation (IPA) at the two
      concentrations analyzed (0.1 and 1.4 MUg/MUL) compared to ADP-induced aggregation
      of PRP. Mitochondrial respiratory parameters and organelle structure assays were
      used to elucidate the action of the compound in this organelle. The exposure of
      mitochondria to crotamine caused a decrease in oxidative phosphorylation and
      changes in mitochondrial permeability, without causing damage in the
      mitochondrial redox state. Together, these results support the hypothesis that,
      besides the antimicrobial potential, crotamine acts on different molecular
      targets, inducing platelet aggregation and mitochondrial dysfunction.

PMID- 29574215
TI  - Lactobacillus plantarum alleviate aflatoxins (B1 and M1) induced disturbances in
      the intestinal genes expression and DNA fragmentation in mice.
AB  - This study aimed to assess the disturbances in intestinal genes expression and
      DNA fragmentation in mice treated orally with aflatoxin B1 (AFB1) or aflatoxin M1
      (AFM1) and the protective activity of Lactobacillus plantarum (LP). Male Balb/c
      mice were divided into 6 groups including the control group, the group treated
      with 2 mg/kg b.w of LP (2 * 109 cfu/mL), the groups treated with AFB1 or AFM1
      (100 MUg/kg b.w), and the groups treated with AFB1 or AFM1 during, after or
      before LP. Small intestines were collected for the determination of DNA
      fragmentation, gene expression and target protein content. The results showed
      that AFB1 or AFM1 increased DNA fragmentation, down regulated the expressions of
      caspase-3, caspase-9, CYP3A13, Bax and p53 as well as up-regulated the expression
      of TNF-alpha and Bcl-2 and their target proteins. LP succeeded to alleviate the
      disturbances in DNA fragmentation and the expression of these genes. The
      improvement was more pronounced in the group co-administered with the toxins plus
      LP. It could be concluded that AFB1 and AFM1 induced disturbances in intestinal
      function via the disturbances in DNA fragmentation and genes expression. LP
      induced a potential protective effect and is considered a promising agent against
      the genotoxicity induced by these mycotoxins.

PMID- 29574216
TI  - Activity-based anorexia activates CRF immunoreactive neurons in female rats.
AB  - Activity-based anorexia (ABA) is a well-established animal model mimicking the
      eating disorder anorexia nervosa (AN). Since the pathophysiology of AN is yet
      poorly understood and specific drug treatments are lacking so far, animal models
      might be useful to further understand this disease. ABA consists of time
      restricted access to food for 1.5 h/day and the possibility to exercise in a
      running wheel for 24 h/day. This combination leads to robust body weight loss as
      observed in AN. Here, we investigated the activation of brain corticotropin
      releasing factor (CRF) neurons, a transmitter involved in the response to stress,
      emotional processes and also food intake. After development of ABA, rat brains
      were processed for c-Fos and CRF double immunohistochemistry. ABA increased the
      number of c-Fos/CRF double labeled neurons in the paraventricular nucleus (PVN)
      and the dorsomedial hypothalamic nucleus (DMH) compared to the ad libitum (AL, ad
      libitum fed, no running wheel) and activity (AC, ad libitum fed, running wheel, p
      < 0.05) but not to the restricted feeding (RF, food for 1.5 h/day, no running
      wheel, p > 0.05) group. Also the number of CRF neurons was increased in the DMH
      of ABA rats compared to AL and AC (p < 0.05). In the Edinger-Westphal nucleus
      (EW) the number of c-Fos positive neurons was increased in ABA and RF compared to
      AC (p < 0.05), while the number of double labeled neurons was not different (p >
      0.05). Taken together, brain CRF activated under conditions of ABA might play a
      role in the development and maintenance of this animal model and possibly also in
      human AN.

PMID- 29574217
TI  - The impact of ALDH2 activation by Alda-1 on the expression of VEGF in the
      hippocampus of a rat model of post-MI depression.
AB  - Post-MI depression is a critical clinical problem, the comorbidity of which
      complicates depression treatment and worsens cardiovascular outcomes. However,
      which antidepressant is the best to lower the risk of cardiovascular events in
      persons with depression was still unknown. Recently, it has been proposed that
      the activation of ALDH2 by Alda-1 can effectively reduce depressive-like
      behaviors and improve the prognosis of coronary heart disease. In the present
      study, we investigated the effect of Alda-1 on the expression of VEGF in the
      hippocampus of a rat model with post-MI depression, as well as the potential
      treatment mechanism. Alda-1 administration significantly decreased the immobility
      time and increased the swimming time of the post-MI depression rats in the forced
      swim test. Moreover, treatment of post-MI depression rats with Alda-1
      significantly increased the sucrose preference ratio, as assessed by a sucrose
      preference test. These behaviors were associated with an increase 5-HT and DA
      neurotransmitter content, as well as an increase of VEGF levels in the
      hippocampus of the post-MI depression rats. These results suggest that Alda-1
      improves depressive-like behavior in rats after MI by increasing VEGF expression
      in the hippocampus of rats.

PMID- 29574218
TI  - Central irisin administration suppresses thyroid hormone production but increases
      energy consumption in rats.
AB  - Irisin, which is secreted from the skeletal muscle in response to physical
      exercise and defined as a thermogenic peptide, may play an important role in
      energy metabolism. Thyroid hormones, which are one of the other influential
      factors on the metabolic status, increase heat production and are the main
      regulators of energy metabolism. This study was conducted to determine the
      possible effects of irisin administration on thyroid hormones. Forty adult male
      Wistar albino rats were used in the study. The rats were equally divided into 4
      groups (n = 10). The brain infusion kit was implanted in the groups, and irisin
      (or solvent as control) was centrally administered to the rats via osmotic mini
      pumps for 7 days. During the experiment, food consumption, body weights, and body
      temperatures of the animals were recorded. Food intake was significantly
      increased in the groups treated with irisin (p < 0.05), but their body weights
      were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4
      levels were significantly lower in the groups treated with irisin as compared to
      the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA
      expression in white and brown adipose tissue and UCP3 mRNA expression in muscle
      tissue in rats and also raised their body temperature (p < 0.05). Consequently,
      although central irisin administration has inhibitory effects on the hypothalamic
      pituitary-thyroid axis, it seems to be an important agent in the regulation of
      food intake and energy metabolism.

PMID- 29574219
TI  - Shaping neurodevelopment: distinct contributions of cytoskeletal proteins.
AB  - Development of a neuron critically depends on the organization of its
      cytoskeleton. Cytoskeletal components, such as tubulins and actins, have the
      remarkable ability to organize themselves into filaments and networks to support
      specialized and compartmentalized functions. Alterations in cytoskeletal proteins
      have long been associated with a variety of neurodevelopmental disorders. This
      review focuses on recent findings, primarily from forward genetic screens in
      Caenorhabditis elegans that illustrate how different tubulin protein isotypes can
      play distinct roles in neuronal development and function. Additionally, we
      discuss studies revealing new regulators of the actin cytoskeleton, and highlight
      recent technological advances in in vivo imaging and functional dissection of the
      neuronal cytoskeleton.

PMID- 29574220
TI  - Long-Term Outcome of Nonfunctioning and Hormonal Active Pituitary Adenoma After
      Gamma Knife Radiosurgery.
AB  - INTRODUCTION: Stereotactic radiosurgery (SRS), particularly Gamma Knife
      radiosurgery (GKRS) is an established treatment option for residual and recurrent
      pituitary adenoma tumors. It helps in the preservation of surrounding normal
      neuronal, vascular, and hormone-producing structures and causes fewer neurologic
      deficits. The aim of this research was to evaluate the efficacy and define the
      role of GKRS in the treatment of nonfunctioning (NFA) and hormonal active (HAA)
      pituitary adenoma. METHODS: A retrospective analysis of 111 patients with
      histologically proven pituitary adenoma who underwent GKRS treatment at Louisiana
      State University Health Sciences Center, Shreveport, Louisiana, USA, over a 17
      year period was conducted presented. The clinical and radiologic data were
      collected from the database. The tumors were categorized into NFA and HAA based
      on the endocrinology profile. The relevant statistical analysis was conducted
      with SPSS software, version 22.0. RESULTS: The median age of the patients was 58
      years. The study comprised 87 patients with NFA and 24 patients with HAA tumors.
      Thirty-eight patients (34.2%) had hypopituitarism symptoms, and 8 patients (7%)
      had panhypopituitarism symptoms. The mean tumor volume before to GKRS was 3.8
      cm3. Suprasellar and cavernous extension of the tumor was noted in 28 patients
      (25.2%) and 34 (30.6%) patients, respectively. We observed >70% reduction in the
      size of tumors in the shrinkage cohort after GKRS; the median time for shrinkage
      was 48.4 months. However, increase in tumor size was noted in the progression
      cohort (pre-GKRS 3.8 cm3 vs. post-GKRS 6.5 cm3). Seventy patients (63.1%) had
      neurologic improvement, and 26 patients (23.4%) had endocrinologic worsening
      after GKRS. CONCLUSIONS: GKRS plays a significant role in the treatment of NFA
      and HAA. It affords a high rate of tumor control and offers a low risk of
      collateral neurologic or endocrine axis injury. Our study shows that control of
      tumor growth was achieved in 90% of patients, shrinkage of tumor in 54%, and
      arrest of progression in 36% after GKRS treatment. The biochemical remission rate
      in growth hormone secreting adenoma was 57%, in adrenocorticotropic hormone
      adenoma 67%, and prolactinoma 40%. Age below 50 years and tumor volume less than
      5 cm3 were associated with a favorable radiosurgical outcome.

PMID- 29574221
TI  - Endoscopic Endonasal Clipping of Anterior Circulation Aneurysm: Surgical
      Techniques and Results.
AB  - BACKGROUND: Endoscopic endonasal clipping of intracranial aneurysms may use
      microsurgical techniques as an alternative to the transcranial approach. Here we
      report a series of patients who underwent microsurgical clipping of anterior
      circulation aneurysms via an endoscopic endonasal approach (EEA). METHODS: This
      retrospective chart review included all the patients who underwent standard
      binostril EEA for aneurysm clipping. Surgical outcomes and complications are
      noted. The rationality and limitations of this procedure are discussed. RESULTS:
      Seven patients with 12 aneurysms of the anterior circulation underwent EEA for
      clipping. These 12 aneurysms consisted of 5 anterior communicating artery (AComA)
      aneurysms, 4 paraclinoid aneurysms, 1 ophthalmic artery aneurysm, and 2 aneurysm
      located in the cavernous segment of internal carotid artery (ICA). Nine of the 12
      aneurysms were successfully clipped. One giant paraclinoid aneurysm could not be
      clipped during operation and was coiled in second endovascular stage. The 2
      aneurysms located in the cavernous segment of ICA were not clipped intentionally
      in a single-stage procedure, after weighing the surgical benefit against the
      difficulty of surgical exposure and feasibility. The proximal control of ICA was
      achieved in all cases. There was no death, no cerebrospinal fluid leak, or other
      complications. All patients recovered completely. CONCLUSIONS: EEA can provide
      direct access for microsurgical clipping of strictly selected anterior
      circulation aneurysms. All the principles of cerebrovascular surgery must be
      followed. These procedures require a long learning curve. Only teams with
      adequate experience in microvascular and endoscopic skull base surgeries should
      attempt this approach for treating aneurysms.

PMID- 29574222
TI  - The Dilemma of Anticoagulating Patients with Cerebral Venous Thrombosis Who
      Underwent Decompressive Craniectomy.
AB  - BACKGROUND: Cerebral venous thrombosis is an uncommon subtype of cerebrovascular
      accident. The appropriate time interval between decompressive craniectomy and the
      onset of anticoagulation in patients with cerebral venous thrombosis is a
      controversial topic among neurosurgeons, neurologists, and intensivists. CASE
      DESCRIPTION: We present a brief clinical case report of a female patient who
      underwent decompressive craniectomy. Cerebral venous thrombosis was subsequently
      diagnosed, and anticoagulation was initiated 24 hours postoperatively.
      CONCLUSIONS: Early onset of anticoagulation is important for a favorable outcome.
      Clinical decision making should rely on the following: 1) postoperative imaging
      studies with no evidence of increase in hematoma, 2) intracranial pressure
      monitoring for patients on mechanical ventilation, and 3) protocols for immediate
      suspension of anticoagulants and use of antagonistic drugs in case of an increase
      in a pre-existing intracranial hemorrhage.

PMID- 29574223
TI  - Spinal Sclerosing Epithelioid Fibrosarcoma at the Cervicothoracic Junction.
AB  - BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is an unusual variant of
      fibrosarcoma that was previously considered to be a low-grade tumor with an
      indolent course. To our knowledge, the spine is a rare primary site for SEF, with
      only a few cases reported to date. CASE DESCRIPTION: We report a case of SEF
      occurring in the cervicothoracic spine of a 64-year-old man with complaints of
      neck pain and right hand tingling for 6 months before clinical presentation.
      Imaging revealed a large mass that extended from C5 to T1 in the right posterior
      paraspinal soft tissues, with involvement of the posterior elements from C6 to T1
      and infiltration of the T1 vertebral body. We performed an en bloc spondylectomy
      and gross total resection of the tumor. Pathologic and immunohistochemical
      characteristics confirmed the diagnosis of SEF. CONCLUSIONS: Because of the
      anatomic nature of the cervicothoracic spine and critical neurovascular
      structures that the tumor involves, a true en bloc resection might not be
      possible, but an oncologically sound excision is ideal.

PMID- 29574224
TI  - The Incidence and Impact of Secondary Cerebral Insults on Outcome After
      Aneurysmal Subarachnoid Hemorrhage.
AB  - INTRODUCTION: Secondary cerebral insults can adversely affect patients with
      traumatic brain injury. By contrast, the incidence of secondary cerebral insults
      after aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have
      been less well studied. METHODS: Four hundred and twenty-one patients with SAH
      who underwent surgical occlusion of their ruptured aneurysm and who received
      intensive care unit care for >=48 hours were retrospectively identified from a
      prospective observational database. Patients were managed according to standard
      recommendations for SAH. Three secondary cerebral insults were examined:
      hypotension (<90 mmHg systolic), hypoxia (Pao2 <60 mm Hg), and hyperglycemia
      (>200 mg/dL). RESULTS: A secondary cerebral insult was observed in 309 (73.4%)
      patients including 135 (32.1%) who had multiple insults. There was an association
      between worse clinical grade and development of secondary insults (P = 0.0002),
      particularly multiple insults (P < 0.0001). When stratified by clinical grade,
      single (adjusted odds ratio [OR], 2.23; 95% confidence interval [CI], 1.10-4.51;
      P = 0.026) and multiple (adjusted OR, 4.37; 95% CI, 2.14-8.93; P < 0.0001)
      secondary cerebral insults were associated with worse outcome. In multivariate
      analysis and controlling for age, admission clinical grade, severity of SAH on
      computed tomography, intracerebral hematoma, increased intracranial pressure (>20
      mm Hg), rebleed, intraoperative rupture, and hydrocephalus, secondary cerebral
      insults were independently associated with poor outcome (adjusted OR, 2.45; 95%
      CI, 1.20-5.02; P = 0.014). CONCLUSIONS: Secondary cerebral insults (hypoxia,
      hypotension, and hyperglycemia) are common after SAH, including among patients
      with a good clinical grade. These insults after SAH are associated with worse
      outcome. These data suggest that prevention of secondary cerebral insults may
      provide an opportunity to improve patient outcome after SAH.

PMID- 29574225
TI  - Dioscin alleviates non-alcoholic fatty liver disease through adjusting lipid
      metabolism via SIRT1/AMPK signaling pathway.
AB  - Dioscin, one natural product, has active effect against non-alcoholic fatty liver
      disease (NAFLD) in our previous work. However, the pharmacological data are
      insufficient and the mechanisms have not been reported. Thus, this study aims to
      comprehensively investigate the effects and molecular mechanisms of dioscin
      against NAFLD. The primary cultured hepatocytes, AML-12 and HepG-2 cells were
      treated with palmic acid (PA) after dioscin treatment. The mice and rats were
      induced by high fat diet to establish the in vivo models of NAFLD. Dioscin
      obviously alleviated liver lipid accumulation symptoms and improved the levels of
      serum and hepatic biochemical parameters in vitro and in vivo. Further
      investigations revealed that dioscin significantly attenuated lipid metabolism
      via adjusting SIRT1/AMPK signal pathway to regulate the expression levels of
      SREBP-1c, CPT, FAS, SCD, FoxO1 and ATGL. In addition, suppression of SIRT1 by
      Nicotinamide or abrogation of AMPK by Compound C eliminated the inhibitory
      effects of dioscin on lipid metabolism. Therefore, our findings further
      demonstrated that dioscin markedly prevented NAFLD through adjusting lipid
      metabolism via SIRT1/AMPK signal pathway, which should be developed as a new
      candidate for NAFLD.

PMID- 29574226
TI  - Role of ASIC1a in Abeta-induced synaptic alterations in the hippocampus.
AB  - Acid-sensing ion channels (ASICs) are widely expressed in the mammalian central
      nervous system where they play a key role in synaptic transmission and in
      specific forms of memory. On the other hand, ASICs can be persistently active
      under pathological conditions contributing to neuronal damage in ischemic stroke,
      brain trauma, epilepsy and Parkinson's disease. However, to date no experimental
      evidence has linked ASICs to Alzheimer's disease (AD). Aim of the present work
      was to investigate, in CA1 pyramidal neurons, the possible involvement of ASIC1a
      in the Abeta-mediated effect on metabotropic glutamate (mGlu) receptor dependent
      transmission. We found that, in slices pretreated with Abeta, the pharmacological
      blockade of ASIC1a restored the increased intrinsic excitability following group
      I mGlu receptor activation. This suggests that, under certain conditions, ASIC1a
      might further contribute to the Abeta-related depolarizing response. We have
      recently demonstrated that ASIC1a is also involved long-term depression (LTD)
      induced either by low-frequency stimulation or by application of the group I mGlu
      receptor agonist DHPG. Here, we have shown that psalmotoxin-1, a selective
      blocker of ASIC1a, rescued the DHPG-LTD facilitation associated with genetic and
      non-genetic models of AD. Overall, these results suggest that a functional
      coupling between ASIC1a and mGlu receptors occurs and might contribute to the
      synaptic alterations associated with AD.

PMID- 29574227
TI  - mTOR signaling in the nucleus accumbens mediates behavioral sensitization to
      methamphetamine.
AB  - Chronic psychostimulant treatment in rodents readily produces behavioral
      sensitization, which reflects altered brain function in response to repeated drug
      exposure. Numerous morphological and biochemical investigations implicate altered
      neural plasticity in striatal medium spiny neurons (MSNs) as an essential
      component in behavioral sensitization. The mammalian target of the rapamycin
      (mTOR) signaling pathway, a key regulator of synaptic neuroplasticity, in the
      ventral striatum of methamphetamine (METH) -sensitized mice was investigated to
      determine if a link exists with the development of METH sensitization.
      Behaviorally, METH-sensitized mice possessed increased levels of phosphorylated
      mTOR/S2448 and its down-stream regulator p70S6K and pS6 in the ventral striatum.
      Systemic treatment with rapamycin, a specific mTOR inhibitor, coincident with a
      daily METH injection suppressed the induction of METH sensitization and reduced
      the number of dendritic spines in the shell and core of the nucleus accumbens.
      The infusion of lentivirus-expressing mTOR-shRNA into the shell region of the
      nucleus accumbens inhibited the induction of behavioral sensitization to METH,
      which was comparable to the effect of rapamycin. These results suggest that
      mTORC1-mediated signaling in the nucleus accumbens mediates the development of
      behavioral sensitization to METH.

PMID- 29574228
TI  - A Platform for Preparing Homogeneous Proteinaceous Subvisible Particles With
      Distinct Morphologies.
AB  - Regulatory authorities and scientific communities are increasingly attentive to
      the known and universal presence of small particulates in biological drug
      products. The underlying concern is that these particulates may cause unwanted
      formation of antidrug antibodies in patients. Pharmacological studies, however,
      have to date not succeeded in unambiguously identifying risk-prone particle
      properties. This lack of success may be partly due to a lack of available, well
      defined, homogenous particle material. Protein particles arising from stress of
      protein drug products are by nature often highly heterogeneous in size,
      morphology, and structure of the constituent protein in the particles. Here, we
      present simple and pharmaceutically relevant stress conditions to produce 8
      different highly homogenous micrometer-sized protein particles from human
      insulin, representing very different morphologies and conformation of the
      constituent protein molecules in the particles generated. Insulin's self
      association patterns were varied by formulation approaches to create diverse
      starting materials. The resulting collection of homogenous particles underlines
      that the particle formation is not necessarily a random process but a consequence
      of formulation and specific stress condition. Owing to the inherent homogenicity
      of these populations, the particle materials can act as a standard platform for
      further studies on insulin subvisible particles in drug products.

PMID- 29574229
TI  - Simple and Robust N-Glycan Analysis Based on Improved 2-Aminobenzoic Acid
      Labeling for Recombinant Therapeutic Glycoproteins.
AB  - N-glycans of therapeutic glycoproteins are critical quality attributes that
      should be monitored throughout all stages of biopharmaceutical development. To
      reduce both the time for sample preparation and the variations in analytical
      results, we have developed an N-glycan analysis method that includes improved 2
      aminobenzoic acid (2-AA) labeling to easily remove deglycosylated proteins. Using
      this analytical method, 15 major 2-AA-labeled N-glycans of Enbrel(r) were
      separated into single peaks in hydrophilic interaction chromatography mode and
      therefore could be quantitated. 2-AA-labeled N-glycans were also highly
      compatible with in-line quadrupole time-of-flight mass spectrometry (MS) for
      structural identification. The structures of 15 major and 18 minor N-glycans were
      identified from their mass values determined by quadrupole time-of-flight MS.
      Furthermore, the structures of 14 major N-glycans were confirmed by interpreting
      the MS/MS data of each N-glycan. This analytical method was also successfully
      applied to neutral N-glycans of Humira(r) and highly sialylated N-glycans of
      NESP(r). Furthermore, the analysis data of Enbrel(r) that were accumulated for
      2.5 years demonstrated the high-level consistency of this analytical method.
      Taken together, the results show that a wide repertoire of N-glycans of
      therapeutic glycoproteins can be analyzed with high efficiency and consistency
      using the improved 2-AA labeling-based N-glycan analysis method.

PMID- 29574230
TI  - Exploring a Kinetic Model Approach in Biopharmaceutics: Estimating the Fraction
      Absorbed of Orally Administered Drugs in Humans.
AB  - Increasing costs of research and development in the pharmaceutical industry has
      necessitated a growing interest in the early prediction of human pharmacokinetics
      of drug candidates. Of growing interest is the need to understand oral
      absorption, the most common route of small molecule drug administration. The
      fraction of dose absorbed (%Fa) is considered a critical yet challenging
      parameter to predict. A kinetic model has been developed and tested to provide an
      early prediction of the fraction dose absorbed in humans. Unlike the traditional
      plug-flow model, this model assumes first-order kinetics to estimate the amount
      of drug present in the stomach and small intestine as a function of time and
      calculates the amount of drug released and absorbed during the transit. Other
      variables can be included in calculation as a function of time to better mimic
      the physiological condition with this approach. Absorption efficiency is assigned
      along with %Fa to give a quantitative estimate of the limiting factor for oral
      absorption. The model was tested with literature and in-house compounds. It was
      found that this model gives a good prediction of human %Fa with a correction
      coefficient (R2) of 0.8 and greater between predicted and reported %Fa for all
      compounds.

PMID- 29574231
TI  - Reduced pupil dilation during action preparation in schizophrenia.
AB  - Impairments in cognitive control-the ability to exert control over thoughts and
      actions and respond flexibly to the environment-are well-documented in
      schizophrenia. However, the degree to which experimental task performance
      reflects true cognitive control impairments or more general alterations in
      effort, arousal and/or task preparedness is unclear. Pupillary responses can
      provide insight into these latter factors, as the pupil dilates with degree of
      cognitive effort and response preparation. In the current study, 16 medicated
      outpatients with schizophrenia (SZP) and 18 healthy controls performed a task
      that measures the ability to reactively inhibit and modify a planned action-the
      double-step task. In this task, participants were required to make a saccade to a
      visual target. Infrequently, the target jumped to a new location and participants
      were instructed to rapidly inhibit and change their eye movement plan. Applying a
      race model of performance, we have previously shown that SZP require more time to
      inhibit a planned action. In the current analysis, we measured pupil dilation
      associated with task preparation and found that SZP had a shallower increase in
      pupil size prior to the onset of the trial. Additionally, reduced magnitude of
      the pupil response was associated with negative symptom severity in patients.
      Based on primate neurophysiology and cognitive neuroscience work, we suggest that
      this blunted pupillary response may reflect abnormalities in a general orienting
      response or reduced motivational significance of a cue signifying the onset of a
      preparatory period and that these abnormalities might share an autonomic basis
      with negative symptoms.

PMID- 29574232
TI  - Individual differences in self-reported reward-approach tendencies relate to
      resting-state and reward-task-based fMRI measures.
AB  - In this study, we investigated neural responses during resting-state and reward
      task-based fMRI and how these related to individual differences in self-reported
      reward sensitivity. Resting-state fMRI data were collected from 191 college
      students, and 60 of these individuals further finished a reward-related fMRI
      task. Self-reported reward-approach tendencies were assessed using the behavioral
      activation scale. Behavioral activation scale scores were positively correlated
      with brain activations in the striatum bilaterally during reward processing.
      During rest, behavioral activation scale scores were positively correlated with
      functional connectivity between the left and right striatum and with functional
      connectivity between the right striatum and right middle frontal gyrus. Positive
      correlations were found between task-based striatal activations and the
      functional connectivity between the left and right striatum at rest. These
      results suggest a relationship between striatal task-based reward-related
      activations and resting connectivity strengths that relate to individual
      differences in reward-approach tendencies.

PMID- 29574234
TI  - Reduced distractor interference during vagus nerve stimulation.
AB  - Suppressing irrelevant information in decision making is an essential everyday
      skill. We studied whether this ability could be improved in epileptic patients
      during vagus nerve stimulation (VNS). VNS is known to increase norepinephrine
      (NE) in the brain. NE is thought to improve several aspects of cognitive control,
      including the suppression of irrelevant information. Nineteen epileptic VNS
      patients executed the Eriksen flanker task twice, both during on and off
      stimulation. Distractor interference was indexed by the congruency effect, a
      standard empirical marker of cognitive control. We found a reduced congruency
      effect during stimulation, which indicates an improved ability to suppress
      distractor interference. This effect was only found in patients that are
      clinically determined VNS-responders (n = 10). As VNS increases NE in VNS
      responders, our finding suggests a beneficial role of NE in cognitive control. At
      the same time, it suggests that VNS does not only reduce seizure frequency in
      epileptic patients, but also improves cognitive control.

PMID- 29574233
TI  - Independent contributions of theta and delta time-frequency activity to the
      visual oddball P3b.
AB  - A growing body of work suggests that the P300 (P3) event-related potential (ERP)
      component is better understood as a mixture of task-relevant processes (Polich,
      2007). This converges with earlier time-frequency work suggesting that the P3b is
      primarily composed of centroparietal delta (0.5-3 Hz) and frontocentral theta (3
      7 Hz) activity. Within this study (N = 229), we hope to re-affirm these prior
      ideas and expand upon them in several crucial ways, reassessing how delta and
      theta contribute to the visual oddball P3b through the lens of several recent
      decades of additional P3b research. We provide a comprehensive assessment of how
      theta and delta time-frequency activity contribute to several common variants of
      the time-domain P3b, specifically measuring the target and non-target P3b, as
      well as differences between targets and non-targets, target-to-target interval
      (TTI), and target habituation. Results replicate and extend earlier work
      indicating that delta and theta account for a majority of variance in both the
      target and non-target P3b as well as their respective amplitude differences. They
      also newly indicate that theta and delta activity can have unique contributions
      to TTI differences and target habituation effects. Results in target habituation
      particularly demonstrate how time-frequency analyses can disentangle nuanced
      changes in P3b activity, shedding new light on these complicated phenomena.
      Findings suggest that delta and theta measures index separable processes
      occurring during the P3b, and provide additional support for the idea that they
      index theoretical frontocentral and centroparietal P3 subcomponents.

PMID- 29574235
TI  - Just rewards: 17-Month-old infants expect agents to take resources according to
      the principles of distributive justice.
AB  - Adults expect distributive justice-that rewards are distributed according to the
      principles of equality and equity. Previous research has demonstrated that
      preschool-aged children are sensitive to distributive justice, yet the age at
      which these sensitivities emerge remains unknown. The current research
      demonstrates that 17-month-old infants (N = 84) expect individuals to distribute
      shared resources based on the amount of work each partner contributed to attain
      the resources. These findings provide evidence that sensitivity to two principles
      of distributive justice, equity and equality, emerges much earlier than has
      previously been suggested.

PMID- 29574236
TI  - Equivalent auditory distraction in children and adults.
AB  - There is an ongoing debate about whether children have more problems ignoring
      auditory distractors than adults. This is an important empirical question with
      direct implications for theories making predictions about the development of
      selective attention. In two experiments, the disruptive effect of to-be-ignored
      speech on short-term memory performance of third graders, fourth graders, fifth
      graders, younger adults, and older adults was examined. Three auditory conditions
      were compared: (a) steady state sequences in which the same distractor was
      repeated, (b) changing state sequences in which different distractors were
      presented, and (c) auditory deviant sequences in which a deviant distractor was
      presented in a sequence of repeated distractors. According to the attentional
      resource view, children should exhibit larger disruption by changing and deviant
      sounds due to their poorer attentional control abilities compared with adults.
      The duplex-mechanism account proposes that the auditory deviant effect is under
      attentional control, whereas the changing state effect is not, and thus predicts
      that children should be more susceptible to auditory deviants than adults but
      equally disrupted by changing state sequences. According to the renewed view of
      age-related distraction, there should be no age differences in cross-modal
      auditory distraction because some of the irrelevant auditory information can be
      filtered out early in the processing stream. Children and adults were equally
      disrupted by changing and deviant speech sounds regardless of whether task
      difficulty was equated between age groups or not. These results are consistent
      with the renewed view of age-related distraction.

PMID- 29574237
TI  - Ethical considerations in the uptake of influenza vaccination by healthcare
      workers.
AB  - OBJECTIVES: The World Health Organization (WHO) recommends annual seasonal
      influenza vaccination of healthcare workers (HCWs). Under the current voluntary
      scheme in England, uptake of vaccine in this group remains well below the 75%
      target. A mandatory scheme may improve rates, but raises the ethical issue of
      imposed vaccination. However, the existing voluntary scheme could also
      potentially infringe autonomy if those not wanting to join feel pressured or
      coerced into vaccination. The aim of this study was to explore HCW views and
      experiences with the current influenza vaccination programme. STUDY DESIGN:
      Questionnaire survey. METHODS: Between March 2015 and April 2016, a total of 140
      questionnaires were completed across seven HCW groups, with the demographic,
      vaccination and opinion data statistically analysed using the chi-squared test,
      Kruskal-Wallis test and Mann-Whitney U-test as appropriate. RESULTS: No staff
      group met the national influenza vaccination target of 75% and vaccination rates
      varied between HCW groups. All groups reported some degree of external pressure
      to be vaccinated and there were mixed views on the concept of mandatory
      vaccination, with a lack of certainty over the vaccine's efficacy and/or a lack
      of information the most common reasons for not supporting it. CONCLUSION: The
      current voluntary influenza vaccination scheme has a number of flaws.
      Improvements in the quality and availability of information provided to employees
      may help Trusts increase vaccination rates, or achieve acceptance of any proposed
      mandatory programme.

PMID- 29574238
TI  - Chilaiditi Syndrome Is a Rare Disease With Features That Resemble
      Pneumoperitoneum.

PMID- 29574239
TI  - Anticancer potential of benzothiazolic derivative (E)-2-((2-(benzo[d]thiazol-2
      yl)hydrazono)methyl)-4-nitrophenol against melanoma cells.
AB  - Malignant melanoma is an important type of cancer worldwide due to its
      aggressiveness and poor survival rate. Significant efforts to understand the
      biology of melanoma and approaches to treat the advanced disease are focused on
      targeted gene inhibitors. Frequently mutated genes, such as NRAS, B-RAF and TP53,
      significantly exceed the frequency of mutations of other genes, emphasizing their
      importance for future targeted therapies. Considering the antitumor activity of
      benzothiazolic derivatives, this study aimed to demonstrate the action of
      benzothiazolic (E)-2-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol
      (AFN01) against three established human melanoma cell lines that recapitulate the
      molecular landscape of the disease in terms of its genetic alterations and
      mutations, such as the TP53, NRAS and B-RAF genes. The results presented here
      indicate that AFN01, as a significant cytostatic and cytotoxic drug due to its
      induction of DNA fragmentation, causes single and double DNA strand breaks,
      consequently inhibiting cell proliferation, migration and invasion by promoting
      apoptosis. Our data suggest that AFN01 might be considered as a future
      therapeutic option for managing melanoma.

PMID- 29574240
TI  - Heterocyclic organobismuth (III) compounds containing an eight-membered ring:
      Inhibitory effects on cell cycle progression.
AB  - We previously showed that heterocyclic organobismuth compounds have excellent
      antimicrobial and antitumor potential. These compounds structurally consist of
      either six- or eight-membered rings. Previous research has shown that bi
      chlorodibenzo[c,f][1,5]thiabismocine (Compound 3), an eight-membered ring,
      induced G2/M arrest via inhibition of tubulin polymerization in HeLa cells.
      Additionally, N-tert-butyl-bi-chlorodi-benzo[c,f][1,5]azabismocine (Compound 1),
      another eight-membered ring, exhibited higher cytotoxicity than Compound 3
      against several cancer cell lines, including HeLa and K562. Finally, bi
      chlorophenothiabismin-S,S-dioxide (Compound 5), a six-membered ring, exhibited
      lower antitumor activity than eight-membered ring compounds. In this study, we
      investigated the antimitotic activity of Compounds 1 and 5 in HeLa cells. At low
      concentrations, (0.1 and 0.25 MUM), Compound 1 inhibited cell growth and arrested
      the cell cycle in mitosis. However, 0.5 MUM Compound 1 exhibited no antimitotic
      activity. Conversely, Compound 5 weakly inhibited cell growth and did not
      markedly arrest the cell cycle. Flow cytometry showed that Compound 1 arrested
      the cell cycle at G2/M, resulting in apoptosis. Compound 1 inhibited tubulin
      polymerization as revealed by a cell-free assay, and both Compounds 1 and 3
      inhibited microtubule spindle formation and chromosome alignment during
      prometaphase. These results suggest that eight-membered ring-containing
      organobismuth compounds can induce mitotic arrest by perturbing spindle dynamics.

PMID- 29574241
TI  - Acute disseminated encephalomyelitis, a rare post-malaria neurological
      complication: Case report and review of the literature.
AB  - There are four neurological complications that can occur after malaria treatment
      at a time when the patient is aparasitaemic: delayed cerebellar ataxia, acute
      inflammatory demyelinating polyneuropathy, post-malaria neurological syndrome and
      acute disseminated encephalomyelitis (ADEM). The authors describe a case of a 54
      year-old male who presented with encephalopathy and generalized seizures forty
      three days after complete recovery from acute malaria by Plasmodium falciparum.
      Diagnosis of post-malaria ADEM was made based on the acute onset of the
      neurological symptoms, characteristic findings in magnetic resonance imaging of
      the brain and prompt response to steroid therapy. ADEM is an autoimmune
      demyelinating disease of the central nervous system that usually arises after an
      infection or vaccination. Its occurrence after malaria infection is relatively
      rare, and to the best of our knowledge there are only thirteen cases described in
      the literature.

PMID- 29574242
TI  - Comparative analysis of core genome MLST and SNP typing within a European
      Salmonella serovar Enteritidis outbreak.
AB  - Multi-country outbreaks of foodborne bacterial disease present challenges in
      their detection, tracking, and notification. As food is increasingly distributed
      across borders, such outbreaks are becoming more common. This increases the need
      for high-resolution, accessible, and replicable isolate typing schemes. Here we
      evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution
      reproducible typing of Salmonella enterica (S. enterica) isolates, by its
      application to a large European outbreak of S. enterica serovar Enteritidis. This
      outbreak had been extensively characterised using single nucleotide polymorphism
      (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP
      based analysis, the epidemiological data, and whole genome MLST (wgMLST)
      analysis. Combination of the cgMLST and epidemiological data confirmed that the
      genetic diversity among the isolates predated the outbreak, and was likely
      present at the infection source. There was consequently no link between country
      of isolation and genetic diversity, but the cgMLST clusters were congruent with
      date of isolation. Furthermore, comparison with publicly available Enteritidis
      isolate data demonstrated that the cgMLST scheme presented is highly scalable,
      enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST
      scheme is therefore shown to be a standardised and scalable typing method, which
      allows Salmonella outbreaks to be analysed and compared across laboratories and
      jurisdictions.

PMID- 29574243
TI  - A comparison of the performance of natural hybrids Saccharomyces cerevisiae *
      Saccharomyces kudriavzevii at low temperatures reveals the crucial role of their
      S. kudriavzevii genomic contribution.
AB  - Fermentation performance at low temperature is a common approach to obtain wines
      with better aroma, and is critical in industrial applications. Natural hybrids S.
      cerevisiae * S. kudriavzevii, isolated from fermentations in cold-climate
      European countries, have provided an understanding of the mechanisms of
      adaptation to grow at low temperature. In this work, we studied the performance
      of 23 S. cerevisiae * S. kudriavzevii hybrids at low temperature (8, 12 and 24 
      degrees C) to characterize their phenotypes. Kinetic parameters and spot tests
      revealed a different ability to grow at low temperature. Interestingly, the
      genome content of the S. kudriavzevii in hybrids was moderately correlated with a
      shorter lag phase, and the genetic origin of hybrids influenced their performance
      at low temperature (8  degrees C). The parental expression of cold marker genes
      (NSR1, GUT2 and GPD1) showed that the relative expression of the S. kudriavzevii
      alleles was higher than the expression of the S. cerevisiae alleles in hybrids
      with a better growth at low-temperatures. These results suggest that the genomic
      contribution of S. kudriavzevii to hybrids is important for improving the fitness
      of these strains at low temperature.

PMID- 29574244
TI  - Alpha-momorcharin enhances Tobacco mosaic virus resistance in tobaccoNN by
      manipulating jasmonic acid-salicylic acid crosstalk.
AB  - Alpha-momorcharin (alpha-MMC) is a type-I ribosome inactivating protein (RIP)
      with a molecular weight of 29 kDa found in plants. This protein has been shown to
      be effective against a broad range of human viruses and also has anti-tumor
      activities. However, the mechanism by which alpha-MMC induces plant defense
      responses and regulates the N gene to promote resistance to the Tobacco mosaic
      virus (TMV) is still not clear. By using pharmacological and infection
      experiments, we found that alpha-MMC enhances TMV resistance of tobacco plants
      containing the N gene (tobaccoNN). Our results showed that plants pretreated with
      0.5 mg/ml alpha-MMC could relieve TMV-induced oxidative damage, had enhanced the
      expression of the N gene and increased biosynthesis of jasmonic acid (JA) and
      salicylic acid (SA). Moreover, transcription of JA and SA signaling pathway genes
      were increased, and their expression persisted for a longer period of time in
      plants pretreated with alpha-MMC compared with those pretreated with water.
      Importantly, exogenous application of 1-Aminobenzotriazole (ABT, SA inhibitor)
      and ibuprofen (JA inhibitor) reduced alpha-MMC induced plant resistance under
      viral infection. Thus, our results revealed that alpha-MMC enhances TMV
      resistance of tobaccoNN plants by manipulating JA-SA crosstalk.

PMID- 29574245
TI  - Seeing is believing: Insights from synchrotron infrared mapping for membrane
      fouling in osmotic membrane bioreactors.
AB  - We employed synchrotron infrared (IR) mapping to resolve forward osmosis (FO)
      membrane fouling in osmotic membrane bioreactor (OMBR). Synchrotron IR mapping
      offers a unique perspective to elucidate the fouling mechanisms and associated
      consequences in OMBR operation. We demonstrated the spatial distribution and
      relative intensity of carbohydrate and protein longitudinally along of the fouled
      FO membrane at the conclusion of OMBR operation. Both transmission and attenuated
      total reflection (ATR) modes were used to map the cross-section and surface of
      the fouled FO membrane. Micro X-ray computed tomography revealed patchy, "sand
      dune" features on the membrane surface at the conclusion of OMBR operation.
      Synchrotron IR-ATR mapping demonstrated that the development of membrane fouling
      layer in OMBR operation was initiated by polysaccharide-like carbohydrate,
      followed by layering with protein-like substance, resulting in a characteristic
      "sand-dune" three dimensional feature. Synchrotron FTIR mapping shed light on
      foulant occurrence and accumulation in the draw solution. Strong penetration of
      protein-like substance into membrane matrix was visualised, resulting the
      detection of protein adsorption in the region of membrane supporting layer.

PMID- 29574246
TI  - Cell proliferation influenced by matrix compliance of gelatin grafted poly(d,l
      Lactide) three dimensional scaffolds.
AB  - Surface and mechanical properties of the biomaterials are determinants of
      cellular responses. In our previous study, star-shaped poly(d,l-Lactide)-b
      gelatin (ss-pLG) was reported for possessing improved cellular adhesion and
      proliferation. Here, we extended our investigation to establish the cellular
      compatibility of gelatin-grafted PDLLA with respect to mechanical properties of
      biological tissues. In this view, linear PDLLA-b-gelatin (l-pLG) was synthesized
      and tissue-level compatibility of 1-pLG and ss-pLG against fibroblasts (L929),
      myoblasts (C2C12) and preosteoblasts (MG-63) was examined. The cell proliferation
      of C2C12 was significantly higher within l-pLG scaffolds, whereas L929 showed
      intensified growth within ss-pLG scaffolds. The difference in cell proliferation
      may be attributed to the varying mechanical properties of scaffolds; where the
      stiffness of l-pLG scaffolds was notably higher than ss-pLG scaffolds, most
      likely due to the variable levels of gelatin grafting on the backbone of PDLLA.
      Therefore, gelatin grafting can be used to modulate mechanical property of the
      scaffolds and this study reveals the significance of the matrix stiffness to
      produce the successful 3D scaffolds for tissue engineering applications.

PMID- 29574247
TI  - Comparison of intra-articular hyaluronic acid and methylprednisolone for pain
      management in knee osteoarthritis: A meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVE: We performed a meta-analysis of randomized controlled trials (RCTs) to
      compare the efficacy and safety of intra-articular methylprednisolone and
      hyaluronic acid (HA) in term of pain reduction and improvements of knee function
      in patients with knee osteoarthritis (OA). MATERIALS AND METHODS: The PubMed,
      EMBASE, ScienceDirect, and Cochrane Library databases were systematically
      searched for literature up to January 2018. RCTs involving HA and
      methylprednisolone in knee OA were included. Two independent reviewers performed
      independent data abstraction. The I2 statistic was used to assess heterogeneity.
      A fixed or random effects model was adopted for meta-analysis. All meta-analyses
      were performed by using STATA 14.0. RESULTS: Five RCTs with 1004 patients were
      included in the meta-analysis. The present meta-analysis indicated that there
      were no significant differences in terms of WOMAC pain, physical function and
      stiffness at 4 week, 12 weeks and 26 weeks between HA and methylprednisolone
      groups. No increased risk of adverse events were identified in both groups.
      CONCLUSION: Both HA and methylprednisolone injections were effective therapies
      for patients with knee OA. Methylprednisolone showed comparable efficacy in
      reducing pain and improving functional recovery to HA. And no significant
      difference was found in long-term of follow-up in terms of adverse effects.

PMID- 29574248
TI  - Embryonic-only arsenic exposure alters skeletal muscle satellite cell function in
      killifish (Fundulus heteroclitus).
AB  - Arsenic is a contaminant found worldwide in drinking water and food.
      Epidemiological studies have correlated arsenic exposure with reduced weight gain
      and improper muscular development, while in vitro studies show that arsenic
      exposure impairs myogenic differentiation. The purpose of this study was to use
      Fundulus heteroclitus or killifish as a model organism to determine if embryonic
      only arsenic exposure permanently reduces the number or function of muscle
      satellite cells. Killifish embryos were exposed to 0, 50, 200, or 800 ppb
      arsenite (AsIII) until hatching, and then juvenile fish were raised in clean
      water. At 28, 40, and 52 weeks after hatching, skeletal muscle injuries were
      induced by injecting cardiotoxin into the trunk of the fish just posterior to the
      dorsal fin. Muscle sections were collected at 0, 3 and 10 days post-injury.
      Collagen levels were used to assess muscle tissue damage and recovery, while
      levels of proliferating cell nuclear antigen (PCNA) and myogenin were quantified
      to compare proliferating cells and newly formed myoblasts. At 28 weeks of age,
      baseline collagen levels were 105% and 112% greater in 200 and 800 ppb groups,
      respectively, and at 52 weeks of age, were 58% higher than controls in the 200
      ppb fish. After cardiotoxin injury, collagen levels tend to increase to a greater
      extent and take longer to resolve in the arsenic exposed fish. The number of
      baseline PCNA(+) cells were 48-216% greater in 800 ppb exposed fish compared to
      controls, depending on the week examined. However, following cardiotoxin injury,
      PCNA is reduced at 28 weeks in 200 and 800 ppb fish at day 3 during the recovery
      period. By 52 weeks, there are significant reductions in PCNA in all exposure
      groups at day 3 of the recovery period. Based on these results, embryonic arsenic
      exposure increases baseline collagen levels and PCNA(+) cells in skeletal muscle.
      However, when these fish are challenged with a muscle injury, the proliferation
      and differentiation of satellite cells into myogenic precursors is impaired and
      instead, the fish appear to be favoring a fibrotic resolution to the injury.

PMID- 29574249
TI  - Nanostructured silver fabric as a free-standing NanoZyme for colorimetric
      detection of glucose in urine.
AB  - Enzyme-mimicking catalytic nanoparticles, more commonly known as NanoZymes, have
      been at the forefront for the development of new sensing platforms for the
      detection of a range of molecules. Although solution-based NanoZymes have shown
      promise in glucose detection, the ability to immobilize NanoZymes on highly
      absorbent surfaces, particularly on free-standing substrates that can be feasibly
      exposed and removed from the reaction medium, can offer significant benefits for
      a range of biosensing and catalysis applications. This work, for the first time,
      shows the ability of Ag nanoparticles embedded within the 3D matrix of a cotton
      fabric to act as a free-standing peroxidase-mimic NanoZyme for the rapid
      detection of glucose in complex biological fluids such as urine. The use of
      cotton fabric as a template not only allows high number of catalytically active
      sites to participate in the enzyme-mimic catalytic reaction, the absorbent
      property of the cotton fibres also helps in rapid absorption of biological
      molecules such as glucose during the sensing event. This, in turn, brings the
      target molecule of interest in close proximity of the NanoZyme catalyst enabling
      accurate detection of glucose in urine. Additionally, the ability to extract the
      free-standing cotton fabric-supported NanoZyme following the reaction overcomes
      the issue of potential interference from colloidal nanoparticles during the
      assay. Based on these unique characteristics, nanostructured silver fabrics offer
      remarkable promise for the detection of glucose and other biomolecules in complex
      biological and environmental fluids.

PMID- 29574250
TI  - A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and
      Adult Brain Tumors.
AB  - Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect
      children, are aggressive brain tumors. The survival for patients with
      glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%,
      this figure has stagnated over the past few decades and survivors still contend
      with significant long-term debilitating side effects. The prognosis for
      pineoblastoma is age-dependent, with little chance of a cure for children younger
      than three years. More effective molecularly targeted strategies are urgently
      required to treat these cancers. Hyper-activation of epidermal growth factor
      receptor (EGFR) signaling is characteristic of several different classes of human
      cancers, including a subset of glioblastoma and medulloblastoma. This has
      provided the impetus for the development of a suite of EGFR pathway blockers,
      including second generation irreversible inhibitors, such as dacomitinib. We have
      developed a comprehensive drug evaluation pipeline, including in vitro
      interaction analyses and orthotopic xenograft mouse models, to address the
      efficacy of drugs for brain tumor treatment, enabling the exclusion of
      potentially ineffective treatments and prioritization of truly beneficial novel
      treatments for clinical trial. We used this system to examine the effects of
      dacomitinib as a single agent, or in combination with conventional
      chemotherapeutics, on the growth of human adult and pediatric brain tumor cell
      lines. Dacomitinib inhibited EGFR or EGFRvIII activity in vitro in all three
      tumor types tested, and as a single agent induced a modest increase in survival
      time for mice bearing glioblastoma, which accurately predicted human clinical
      trial data. For pediatric medulloblastoma, dacomitinib blocked EGFR/HER
      signalling in orthotopic xenografts and extended median survival as a single
      agent, however was antagonistic when used in combination with standard frontline
      medulloblastoma chemotherapies. The findings caution against the use of
      dacomitinib for pediatric brain tumor clinical trials.

PMID- 29574251
TI  - Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived
      Xenografts.
AB  - Patient-Derived Xenografts (PDXs), entailing implantation of cancer specimens in
      immunocompromised mice, are emerging as a valuable translational model that could
      help validate biologically relevant targets and assist the clinical development
      of novel therapeutic strategies for gastric cancer. More than 30% of PDXs
      generated from gastric carcinoma samples developed human B-cell lymphomas instead
      of gastric cancer. These lymphomas were monoclonal, Epstein Barr Virus (EBV)
      positive, originated tumorigenic cell cultures and displayed a mutational burden
      and an expression profile distinct from gastric adenocarcinomas. The ability of
      grafted samples to develop lymphomas did not correlate with patient outcome, nor
      with the histotype, the lymphocyte infiltration level, or the EBV status of the
      original gastric tumor, impeding from foreseeing lymphoma onset. Interestingly,
      lymphoma development was significantly more frequent when primary rather than
      metastatic samples were grafted. Notably, the development of such lympho
      proliferative disease could be prevented by a short rituximab treatment upon mice
      implant, without negatively affecting gastric carcinoma engraftment. Due to the
      high frequency of human lymphoma onset, our data show that a careful histologic
      analysis is mandatory when generating gastric cancer PDXs. Such care would avoid
      misleading results that could occur if testing of putative gastric cancer
      therapies is performed in lymphoma PDXs. We propose rituximab treatment of mice
      to prevent lymphoma development in PDX models, averting the loss of human-derived
      samples.

PMID- 29574252
TI  - Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes
      Glioblastoma.
AB  - Emergent evidences revealed that long noncoding RNAs (lncRNAs) participate in
      neoplastic progression. HMMR is an oncogene that is highly expressed in
      glioblastoma (GBM) and supports GBM growth. Whether lncRNAs regulate HMMR in GBM
      remains unknown. Herein, we identify that an HMMR antisense lncRNA, HMMR-AS1, is
      hyperexpressed in GBM cell lines and stabilizes HMMR mRNA. Knockdown of HMMR-AS1
      reduces HMMR expression; inhibits cell migration, invasion, and mesenchymal
      phenotypes; and suppresses GBM cell growth both in vitro and in vivo. Moreover,
      knockdown of HMMR-AS1 radiosensitizes GBM by reducing DNA repair proteins ATM,
      RAD51, and BMI1. Our data demonstrate a mechanism of sense-antisense interference
      between HMMR and HMMR-AS1 in GBM and suggest that targeting HMMR-AS1 is a
      potential strategy for GBM treatment.

PMID- 29574254
TI  - Adverse pregnancy outcomes in women with changing patterns of exposure to the
      emissions of a municipal waste incinerator.
AB  - Municipal solid waste incinerators emissions contain pollutants that, despite
      their low concentration, might adversely affect reproductive health. In the
      present study, we examined rates of miscarriage and birth defects among women who
      resided or were employed in the vicinity of a municipal solid waste incinerator
      plant from 2003 to 2013. In 2009, a progressive shutdown of the old incineration
      lines and operation of a new line caused considerably higher atmospheric release
      of polycyclic aromatic hydrocarbons, particularly of dioxins, due to these
      irregular operating conditions, technological renovation, and increased capacity.
      We used dioxin emission levels, based on a dispersion model, to define exposure
      status of the residing population to air pollutants emitted by the waste
      incinerator. In women who resided in areas characterized by higher emission
      exposures compared with a referent area, the relative risk (RR) of miscarriage
      was 1.04 (95% confidence interval (CI) 0.80-1.32) based on 62 cases overall, with
      little evidence of a dose-response relation. RRs were similarly null for both
      2003-2008 and 2010-2013 periods (RR 1.12 (95% CI 0.80-1.53) and 0.98 (95% CI 0.63
      1.48), respectively). Concerning birth defects in the offspring of women residing
      in the exposed area, no evidence of increased risk emerged, since the prevalence
      ratio at birth was 0.64 (95% CI 0.29-1.26), with comparable results in the 2003
      2008 and 2010-2013 period. Corresponding analyses carried out in municipal
      residents who worked in the exposed area confirmed these findings. We also did
      not detect abnormally high rates of miscarriage and birth defects in the exposed
      cohorts in the single year 2009. Overall, these results do not suggest an effect
      of exposure to the emissions of the municipal solid waste incinerator we
      investigated on two indicators of reproductive health. However, the limited
      statistical stability of the estimates and the absence of individual-based
      information on some potential confounders suggest caution in the interpretation
      of study findings.

PMID- 29574256
TI  - Residential mobility and childhood leukemia.
AB  - AIMS: Studies of environmental exposures and childhood leukemia studies do not
      usually account for residential mobility. Yet, in addition to being a potential
      risk factor, mobility can induce selection bias, confounding, or measurement
      error in such studies. Using data collected for California Powerline Study
      (CAPS), we attempt to disentangle the effect of mobility. METHODS: We analyzed
      data from a population-based case-control study of childhood leukemia using cases
      who were born in California and diagnosed between 1988 and 2008 and birth
      certificate controls. We used stratified logistic regression, case-only analysis,
      and propensity-score adjustments to assess predictors of residential mobility
      between birth and diagnosis, and account for potential confounding due to
      residential mobility. RESULTS: Children who moved tended to be older, lived in
      housing other than single-family homes, had younger mothers and fewer siblings,
      and were of lower socioeconomic status. Odds ratios for leukemia among non-movers
      living <50 meters (m) from a 200+ kilovolt line (OR: 1.62; 95% CI: 0.72-3.65) and
      for calculated fields >= 0.4 microTesla (OR: 1.71; 95% CI: 0.65-4.52) were
      slightly higher than previously reported overall results. Adjustments for
      propensity scores based on all variables predictive of mobility, including
      dwelling type, increased odds ratios for leukemia to 2.61 (95% CI: 1.76-3.86) for
      living < 50 m from a 200 + kilovolt line and to 1.98 (1.11-3.52) for calculated
      fields. Individual or propensity-score adjustments for all variables, except
      dwelling type, did not materially change the estimates of power line exposures on
      childhood leukemia. CONCLUSION: The residential mobility of childhood leukemia
      cases varied by several sociodemographic characteristics, but not by the distance
      to the nearest power line or calculated magnetic fields. Mobility appears to be
      an unlikely explanation for the associations observed between power lines
      exposure and childhood leukemia.

PMID- 29574255
TI  - Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to
      16HBE14o- human bronchial epithelial cells.
AB  - The production and application of engineered nanoparticles (NPs) are increasing
      in demand with the rapid development of nanotechnology. However, there are
      concerns that some of these novel materials could lead to emerging environmental
      and health problems. Some NPs are able to facilitate the transport of
      contaminants into cells/organisms via a "Trojan Horse" effect which enhances the
      toxicity of the adsorbed materials. In this work, we evaluated the toxicity of
      arsenite (As(III)) adsorbed onto cerium dioxide (CeO2) NPs to human bronchial
      epithelial cells (16HBE14o-) using the xCELLigence real time cell analyzing
      system (RTCA). Application of 0.5 mg/L As(III) resulted in 81.3% reduction of
      cell index (CI, an RTCA measure of cell toxicity) over 48 h when compared to
      control cells exposed to medium lacking As(III). However, when the cells were
      exposed to 0.5 mg/L As(III) in the presence of CeO2 NPs (250 mg/L), the CI was
      only reduced by 12.9% compared to the control. The CeO2 NPs had a high capacity
      for As(III) adsorption (20.2 mg/g CeO2) in the bioassay medium, effectively
      reducing dissolved As(III) in the aqueous solution and resulting in reduced
      toxicity. Transmission electron microscopy was used to study the transport of
      CeO2 NPs into 16HBE14o- cells. NP uptake via engulfment was observed and the
      internalized NPs accumulated in vesicles. The results demonstrate that dissolved
      As(III) in the aqueous solution was the decisive factor controlling As(III)
      toxicity of 16HBE14o- cells, and that CeO2 NPs effectively reduced available
      As(III) through adsorption. These data emphasize the evaluation of mixtures when
      assaying toxicity.

PMID- 29574253
TI  - Probing the role of the vestibular system in motivation and reward-based
      attention.
AB  - The vestibular system has widespread connections in the central nervous system.
      Several activation loci following vestibular stimulations have been notably
      reported in deep, limbic areas that are otherwise difficult to reach and modulate
      in healthy subjects. Following preliminary evidence, suggesting that such
      stimulations might affect mood and affective processing, we wondered whether the
      vestibular system is also involved in motivation. Evolutionary accounts suggest
      that visuo-vestibular mismatches might have a role in preventing the search for
      and exploitation of goods that previously resulted in aversive reactions, as they
      would be a fine warning signal which follows the contact with or ingestion of
      noxious neurotoxins. The first question was thus whether vestibular stimulation
      alters sensitivity to reward. Secondly, we sought to assess whether attention is
      allocated in space differently when cued by highly motivational stimuli, and if
      this interplay is further modulated by the vestibular system. In order to
      evaluate both motivational and attentional assets, we administered a Posner-like
      cueing task to 30 healthy subjects concurrently receiving sham or galvanic
      vestibular stimulation (GVS; Left-Anodal and Right-Anodal configurations). The
      participants had to discriminate targets appearing in either exogenously cued or
      uncued locations (50% validity); cues predicted the amount of points (0, 2, or
      10) and thus money that they could earn for a correct response. The results
      highlight a robust inhibition of return (IOR) (faster responses for invalidly
      cued targets) which was not modulated by different levels of reward or GVS.
      Across all stimulation sessions, rewards exerted a powerful beneficial effect
      over performance: reaction times were faster when rewards were at stake. However,
      this effect was largest in sham, but greatly reduced in GVS conditions, most
      notably with the Right-Anodal configuration. This is the first evidence for a
      decreased sensitivity to rewards causally induced by a perturbation of the
      vestibular system. While future studies will shed light on its neural
      underpinnings and clinical implications, here we argue that GVS could be a safe
      and promising way to enrich our understanding of reward processes and eventually
      tackle the management of patients with aberrant sensitivity to rewards.

PMID- 29574257
TI  - Mechanisms underlying weight status and healthcare avoidance in women: A study of
      weight stigma, body-related shame and guilt, and healthcare stress.
AB  - Studies show that women with high BMI are less likely than thinner women to seek
      healthcare. We aimed to determine the mechanisms linking women's weight status to
      their healthcare avoidance. Women (N = 313) were surveyed from a U.S. health
      panel database. We tested a theory-driven model containing multiple stigma and
      body-related constructs linking BMI to healthcare avoidance. The model had a good
      fit to the data. Higher BMI was related to greater experienced and internalized
      weight stigma, which were linked to greater body-related shame. Internalized
      weight stigma was also related to greater body-related guilt, which was
      associated with higher body-related shame. Body-related shame was associated with
      healthcare stress which ultimately contributed to healthcare avoidance. We
      discuss recommendations for a Weight Inclusive Approach to healthcare and the
      importance of enhancing education for health professionals in weight bias in
      order to increase appropriate use of preventive healthcare in higher weight
      women.

PMID- 29574258
TI  - Water relation, leaf gas exchange and chlorophyll a fluorescence imaging of
      soybean leaves infected with Colletotrichum truncatum.
AB  - Considering the potential of anthracnose to decrease soybean yield and the need
      to gain more information regarding its effect on soybean physiology, the present
      study performed an in-depth analysis of the photosynthetic performance of soybean
      leaflets challenged with Colletotrichum truncatum by combining chlorophyll a
      fluorescence images with gas-exchange measurements and photosynthetic pigment
      pools. There were no significant differences between non-inoculated and
      inoculated plants in leaf water potential, apparent hydraulic conductance, net
      CO2 assimilation rate, stomatal conductance to water vapor and transpiration
      rate. For internal CO2 concentration, significant difference between non
      inoculated and inoculated plants occurred only at 36 h after inoculation.
      Reductions in the values of the chlorophyll a fluorescence parameters [initial
      fluorescence (F0), maximal fluorescence (Fm), maximal photosystem II quantum
      yield (Fv/Fm), quantum yield of regulated energy dissipation (Y(NPQ))] and
      increases in effective PS II quantum yield (Y(II)), quantum yield of non
      regulated energy dissipation Y(NO) and photochemical quenching coefficient (qP)
      were noticed on the necrotic vein tissue in contrast to the surrounding leaf
      tissue. It appears that the impact of the infection by C. truncatum on the
      photosynthetic performance of the leaflets was minimal considering the preference
      of the fungus to colonize the veins.

PMID- 29574259
TI  - Dorsal root ganglia pulsed radiofrequency treatment alters the spinal immune
      environment.

PMID- 29574260
TI  - HLA typing using genome wide data reveals susceptibility types for infections in
      a psychiatric disease enriched sample.
AB  - BACKGROUND: The infections Toxoplasma gondii (T. gondii), cytomegalovirus, and
      Herpes Simplex Virus Type 1 (HSV1) are common persistent infections that have
      been associated with schizophrenia and bipolar disorder. The major
      histocompatibility complex (MHC, termed HLA in humans) region has been implicated
      in these infections and these mental illnesses. The interplay of MHC genetics,
      mental illness, and infection has not been systematically examined in previous
      research. METHODS: In a cohort of 1636 individuals, we used genome-wide
      association data to impute 7 HLA types (A, B, C, DRB1, DQA1, DQB1, DPB1), and
      combined this data with serology data for these infections. We used regression
      analysis to assess the association between HLA alleles, infections (individually
      and collectively), and mental disorder status (schizophrenia, bipolar disorder,
      controls). RESULTS: After Bonferroni correction for multiple comparisons, HLA
      C*07:01 was associated with increased HSV1 infection among mentally healthy
      controls (OR 3.4, p = 0.0007) but not in the schizophrenia or bipolar groups (P >
      0.05). For the multiple infection outcome, HLA B* 38:01 and HLA C*12:03 were
      protective in the healthy controls (OR ~ 0.4) but did not have a statistically
      significant effect in the schizophrenia or bipolar groups. T. gondii had several
      nominally-significant positive associations, including the haplotypes HLA
      DRB*03:01 ~ HLA DQA*05:01 ~ HLA DQB*02:01 and HLA B*08:01 ~ HLA C*07:01.
      CONCLUSIONS: We identified HLA types that showed strong and significant
      associations with neurotropic infections. Since some of these associations
      depended on mental illness status, the engagement of HLA-related pathways may be
      altered in schizophrenia due to immunogenetic differences or exposure history.

PMID- 29574261
TI  - The expression of TRPV channels, prostaglandin E2 and pro-inflammatory cytokines
      during behavioural fever in fish.
AB  - A fever, or increased body temperature, is a symptom of inflammation, which is a
      complex defence reaction of the organism to pathogenic infections. After
      pathogens enter the body, immune cells secrete a number of agents, the functions
      of which stimulate the body to develop a functional immune and fever response. In
      mammals it is known that PGE2 is the principal mediator of fever. The extent to
      which PGE2 and other pro-inflammatory cytokines such as TNF-alpha, IL-6, or IL
      1beta could be involved in the induction of behavioural fever in fish remains to
      be clarified. Several members of the transient receptor potential (TRP) family of
      ion channels have been implicated as transducers of thermal stimuli, including
      TRPV1 and TRPV2, which are activated by heat. Here we show that members of the
      TRP family, TRPV1 and TRPV4, may participate in the coordination of temperature
      sensing during the behavioural fever. To examine the behavioral fever mechanism
      in Salmo salar an infection with IPNV, infectious pancreatic necrosis virus, was
      carried out by an immersion challenge with 10 * 105 PFU/mL-1 of IPNV. Behavioural
      fever impacted upon the expression levels of both TRPV1 and TRPV4 mRNAs after the
      viral challenge and revealed a juxtaposed regulation of TRPV channels. Our
      results suggest that an increase in the mRNA abundance of TRPV1 is tightly
      correlated with a significant elevation in the expression of pro-inflammatory
      cytokines (IL-1beta, IL-6, TNF-alpha and PGE2) in the Pre-Optic Area (POA) and
      cytokine release in plasma. Together, these data indicate that the reduction of
      TRPV4 expression during behavioural fever may contribute to the onset of
      behavioural fever influencing movement toward higher water temperatures. Our data
      also suggest an effect of TRPV channels in the regulation of behavioural fever
      through activation of EP3 receptors in the central nervous system by PGE2 induced
      by plasma-borne cytokines. These results highlight for first time in mobile
      ectotherms the key role of pro-inflammatory cytokines and TRPV channels in
      behavioural fever that likely involves a complex integration of prostaglandin
      induction, cytokine recognition and temperature sensing.

PMID- 29574262
TI  - Enacted stigma and felt stigma experienced by adults who stutter.
AB  - PURPOSE: The aim of this study was to (1) document the experiences of enacted
      stigma (external stigma, experienced discrimination) and felt stigma
      (anticipation and expectation of discrimination or negative treatment by others)
      in adults who stutter, (2) investigate their relationships to each other, and (3)
      investigate their relationships to global mental health. METHOD: Participants
      were 324 adults who stutter recruited from clinicians and self-help group leaders
      in the United States. Participants completed an anonymous web survey consisting
      of measures of enacted stigma, felt stigma, and global mental health. Data
      analysis focused on obtaining descriptive statistics for enacted stigma and felt
      stigma, and performing correlational analysis between these variables, and also
      between these variables and global mental health. RESULTS: Most participants
      reported experiencing several different forms of social devaluation and negative
      treatment from other people at some point in their lives (i.e., enacted stigma),
      although they rarely experienced these events during the past year. Most
      participants agreed that they anticipate future stigmatizing experiences (i.e.,
      felt stigma). Enacted stigma in the past year demonstrated a significant positive
      relationship to felt stigma. Both enacted stigma in the past year and felt stigma
      demonstrated significant negative relationships with global mental health.
      Enacted stigma in the past year and felt stigma were unique predictors of
      participants' global mental health. CONCLUSIONS: People who stutter experience
      discrimination and social devaluation, and they anticipate future stigmatizing
      experiences. Both of these types of stigma, enacted and felt, are associated with
      reduced mental health in adults who stutter. Assessment and therapy with adults
      who stutter should address these aspects of stuttering.

PMID- 29574263
TI  - Evaluation of joint effects of cyprodinil and kresoxim-methyl on zebrafish, Danio
      rerio.
AB  - Aquatic organisms are usually exposed to a mixture of pesticides instead of
      individual chemicals. However, risk assessment of pesticides is traditionally
      based on toxicity data of individual compounds. In this study, we aimed to
      examine the joint toxicity of two fungicides cyprodinil (CYP) and kresoxim-methyl
      (KRM) to zebrafish (Danio rerio) using a systematic experimental approach.
      Results from 96-h semi-static test indicated that the LC50 values of KRM to D.
      rerio at multiple life stages (embryonic, larval, juvenile and adult stages)
      ranged from 0.034 (0.015-0.073) to 0.61 (0.39-0.83) mg a.i. L-1, which were
      higher than those of CYP ranging from 1.05 (0.88-1.52) to 4.42 (3.24-6.02) mg
      a.i. L-1. Pesticide mixtures of CYP and KRM exhibited synergistic effect on
      embryonic zebrafish. The activities of carboxylesterase (CarE) and cytochrome
      P450 (Cyp450) were significantly altered in most of the individual and combined
      exposures compared with the control group. The expressions of seven genes (Mnsod,
      cyp17, crhr 2, crh, gnrhr 4, gnrhr 1 and hmgrb) were significantly altered upon
      exposure to combined pesticides compared with their individual pesticides.
      Collectively, these findings suggested joint effects should be considered in the
      risk assessment of pesticides and development of water quality criteria for the
      protection of aquatic environment.

PMID- 29574264
TI  - CO2 switchable hollow nanospheres.
AB  - HYPOTHESIS: Hollow nanospheres, characterized by a cavity inside a solid shell,
      have potential applications due to their unique structure, but the unchangeable
      morphology and permeability of the shell restrain their further practical
      utilization. While several smart hollow nanospheres that can respond to pH, ion
      strength, and temperature have been developed, they are inclined to suffer from
      problems associated with high energy consumption or the difficult removal of
      residual stimulants. Thus, it is desirable to develop a novel and free-of
      residual trigger stimulating mode. EXPERIMENTS: In this work, CO2 is used to
      fabricate smart hollow nanospheres composed of crosslinked poly(diethylamino
      ethyl methacrylate) (PDEAEMA) network from polystyrene (PS)/PDEAEMA core-shell
      nanospheres by a template-removal technique. The morphology evolution of the
      resultant nanospheres during the fabrication process was characterized by X-ray
      photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR),
      thermogravimetry analysis (TGA) and dynamic light scattering (DLS) and was
      visualized by transmission electron microscopy (TEM) and scanning electron
      microscopy (SEM). FINDINGS: Hollow nanospheres can be generated by experiencing a
      morphology change from a core nanosphere, core-shell, yolk-shell to a final
      hollow structure. The increase in shell-stiffness can restrain the collapse of
      hollow spheres. It is demonstrated that CO2 is easy to introduce and remove (via
      N2 input) without stimulation residues in this system. In addition, mild CO2/N2
      purging can only reversibly change the swelling/collapse of hollow particles;
      violent CO2/N2 bubbling can reversibly regulate both the size and aggregation/re
      dispersion state of the hollow nanospheres, which can be intuitively observed by
      atomic force microscopy (AFM).

PMID- 29574265
TI  - Synthesis of raspberry-like polymer/SiO2 hybrid colloidal spheres grafted by
      block-copolymer poly(MPC-b-MPS) for underwater superoleophobic anti-biofouling
      coatings.
AB  - Raspberry-like polymer/inorganic compound hybrid colloidal spheres have attracted
      tremendous interest owing to their many potential applications, but most of them
      are concentrated on synthesis methods, controlling structures and morphologies.
      Herein, we synthesize raspberry-like poly(ethyl methacrylate)/SiO2 colloidal
      spheres and further graft a hydrophilic diblock copolymer on the SiO2
      nanoparticles. The obtained copolymer-grafted hybrid sphere-based coatings are
      robust and display excellent underwater superoleophobic and anti-biofouling
      performances as well as self-repairing ability.

PMID- 29574266
TI  - Novel Ag-Cu bimetallic alloy decorated near-infrared responsive three-dimensional
      rod-like architectures for efficient photocatalytic water purification.
AB  - In this paper, novel silver-copper bimetallic alloy (Ag-Cu) nanoparticles (NPs)
      decorated beta-NaYF4: Yb3+, Tm3+@TiO2 ("@" means TiO2 supported on NaYF4: Yb3+,
      Tm3+, marked as NYFT) micro-rods were successfully synthesized through a
      surfactant-assistant sol-gel method and H2 reduction process for the first time.
      In NYFT@Ag-Cu composite, efficient energy transfer from beta-NaYF4: Yb3+, Tm3+
      (NYF) to TiO2 and metal NPs was confirmed. Under near-infrared (NIR) light
      irradiation, Ag-Cu alloy supported NYFT exhibited significantly enhanced
      photocatalytic activity in comparison with other samples, and water disinfection
      involving 100% inactivation of bacteria was realized within 8 h. The strengthened
      photocatalytic activity was assigned to the synergistic effect of up-conversion
      (UC) material and alloy NPs. Some reasons for the improved photocatalytic
      activity were systematically investigated and a probable mechanism for NIR
      responsive photocatalysis was elucidated.

PMID- 29574267
TI  - Carbon nanofibers wrapped with zinc oxide nano-flakes as promising electrode
      material for supercapacitors.
AB  - A combination of electrospinning technique and hydrothermal process was carried
      out to fabricate zinc oxide nano-flakes wrapped carbon nanofibers (ZnO/CNFs)
      composite as an effective electrode material for supercapacitor. The morphology
      of the as-synthesized composite clearly revealed that the carbon nanofibers were
      successfully wrapped with ZnO nano-flakes. The electrochemical performance of the
      as-synthesized nanocomposite electrode was evaluated by the cyclic voltammetry
      (CV), galvanostatic charge-discharge (GDC), and electrochemical impedance
      spectroscopy (EIS), and compared with the pristine ZnO nanofibers. It was found
      that the composite exhibited a higher specific capacitance (260 F/g) as compared
      to pristine ZnO NFs (118 F/g) at the scan rate of 5 mV/s. Furthermore, the
      ZnO/CNFs composite also exhibited good capacity retention (73.33%). The obtained
      results indicated great potential applications of ZnO/CNFs composite in
      developing energy storage devices with high energy and power densities. The
      present work might provide a new route for utilizing ZnO based composites for
      energy storage applications.

PMID- 29574268
TI  - Fluid flow simulations meet high-speed video: Computer vision comparison of
      droplet dynamics.
AB  - HYPOTHESIS: While multiphase flows, particularly droplet dynamics, are ordinary
      in nature as well as in industrial processes, their mathematical and
      computational modelling continue to pose challenging research tasks - patent
      approaches for tackling them are yet to be found. The lack of analytical flow
      field solutions for non-trivial droplet dynamics hinders validation of computer
      simulations and, hence, their application in research problems. High-speed videos
      and computer vision algorithms can provide a viable approach to validate
      simulations directly against experiments. EXPERIMENTS: Droplets of water (or
      glycerol-water mixtures) impacting on both hydrophobic and superhydrophobic
      surfaces were imaged with a high-speed camera. The corresponding configurations
      were simulated using a lattice-Boltzmann multiphase scheme. Video frames from
      experiments and simulations were compared, by means of computer vision, over
      entire droplet impact events. FINDINGS: The proposed experimental validation
      procedure provides a detailed, dynamic one-on-one comparison of a droplet impact.
      The procedure relies on high-speed video recording of the experiments, computer
      vision, and on a software package for the analyzation routines. The procedure is
      able to quantitatively validate computer simulations against experiments and it
      is widely applicable to multiphase flow systems in general.

PMID- 29574269
TI  - A simple way to an ultra-robust superhydrophobic fabric with mechanical
      stability, UV durability, and UV shielding property.
AB  - HYPOTHESIS: Development of an ultra-robust superhydrophobic fabric with
      mechanical stability, UV durability, and UV shielding by a simple method is
      highly desirable, yet it remains a challenge that current technologies have been
      unable to fully address. EXPERIMENTS: Herein, the original fabric is immersed
      into the solution containing ZnO nanoparticle and PDMS (polydimethylsiloxane),
      and the fiber surfaces are uniformly covered by a ZnO-PDMS layer after thermal
      treatment at 110  degrees C for 30 min. FINDINGS: Droplets of water and corrosive
      liquids including strong acid, strong alkali, and saturated salt solution display
      sphere shape on the ZnO-PDMS coated fabric surface. The stable binding of ZnO
      PDMS layer onto the fibers allows for the fabric coating with robust
      superhydrophobicity, and the coated fabric still displays superhydrophobicity
      after hand twisting, knife scratching, finger touching, and even cycles of
      sandpaper abrasion. The ZnO-PDMS coated fabric can also keep its superhydrophobic
      property when exposed to long term UV illumination, demonstrating its UV
      resistance. Moreover, the uniformly distribution of ZnO nanoparticles on fibers
      allows the ZnO-PDMS coated fabric to display UV shielding property.

PMID- 29574270
TI  - Self-assembling behavior of pyrimidine analogues: Unveiling the factors behind
      morphological diversity.
AB  - Studying the self-assembly of uracil derivatives has great importance in
      biochemistry and nanotechnology. Now, in order to architect unique and
      interesting nucleobase nanostructures, herein, we report a simple, yet robust
      uracil moiety based platform which is potentially capable to self-assemble into
      fibrils. The system is validated using eight uracil moiety derivatives and the
      effect is examined via fluorescence lifetime imaging microscopy (FLIM), field
      emission scanning electron microscopy (FESEM), steady state DCM fluorescence and
      fluorescence correlation spectroscopy (FCS). FLIM and FESEM give qualitative
      information regarding the fibril formation of different morphologies including
      string, rod, flower, needles etc. Steady state DCM fluorescence and FCS establish
      a quantitative estimation of the extent of fibril formation. The involvement of
      hydrogen bonding interaction between NH and CO groups in the fibrillar growth of
      5-IU is evoked from the crystallographic study. Again, the key role of different
      functional groups behind the formation of fibrillar network is investigated
      through blocking the COO- group of orotic acid with lanthanides. Finally,
      esterification and N,N'-dimethylation exquisitely explore the role and priority
      of different groups in the fibril formation of pyrimidine analogues. The results
      may be useful for understanding the processes of self-assembly of the uracil
      derivatives and the rationalized design of the uracil based supramolecular
      structures with specific properties.

PMID- 29574271
TI  - Recent radiation and dispersal of an ancient lineage: The case of Fouquieria
      (Fouquiericeae, Ericales) in North American deserts.
AB  - Arid biomes are particularly prominent in the Neotropics providing some of its
      most emblematic landscapes and a substantial part of its species diversity. To
      understand some of the evolutionary processes underlying the speciation of
      lineages in the Mexican Deserts, the diversification of Fouquieria is
      investigated, which includes eleven species, all endemic to the warm deserts and
      dry subtropical regions of North America. Using a phylogeny from plastid DNA
      sequences with samples of individuals from populations of all the species
      recognized in Fouquieria, we estimate divergence times, test for temporal
      diversification heterogeneity, test for geographical structure, and conduct
      ancestral area reconstruction. Fouquieria is an ancient lineage that diverged
      from Polemoniaceae ca. 75.54 Ma. A Mio-Pliocene diversification of Fouquieria
      with vicariance, associated with Neogene orogenesis underlying the early
      development of regional deserts is strongly supported. Test for temporal
      diversification heterogeneity indicates that during its evolutionary history,
      Fouquieria had a drastic diversification rate shift at ca.12.72 Ma, agreeing with
      hypotheses that some of the lineages in North American deserts diversified as
      early as the late Miocene to Pliocene, and not during the Pleistocene. Long-term
      diversification dynamics analyses suggest that extinction also played a
      significant role in Fouquieria's evolution, with a very high rate at the onset of
      the process. From the late Miocene onwards, Fouquieria underwent substantial
      diversification change, involving high speciation decreasing to the present and
      negligible extinction, which is congruent with its scant fossil record during
      this period. Geographic phylogenetic structure and the pattern of most sister
      species inhabiting different desert nucleus support that isolation by distance
      could be the main driver of speciation.

PMID- 29574272
TI  - The Microtus voles: Resolving the phylogeny of one of the most speciose mammalian
      genera using genomics.
AB  - Sequential rapid radiations pose some of the greatest difficulties in
      phylogenetics, especially when analysing only a small number of genetic markers.
      Given that most of the speciation events occur in quick succession at various
      points in time, this creates particular challenges in determining phylogenetic
      relationships, i.e. branching order and divergence times. With the development of
      high throughput sequencing, thousands of markers can now readily be used to
      tackle these issues. Microtus is a speciose genus currently composed of 65
      species that evolved over the last 2 million years. Although it is a well-studied
      group, there is still phylogenetic uncertainty at various divergence levels.
      Building upon previous studies that generally used small numbers of mitochondrial
      and/or nuclear loci, in this genomic-scale study we used both mitochondrial and
      nuclear data to study the rapid radiation within Microtus, using partial
      mitogenomes and genotyping-by-sequencing (GBS) on seven species representing five
      Microtus subgenera and the main biogeographic ranges where this group occurs.
      Both types of genome (mitochondrial and nuclear) generated similar tree
      topologies, with a basal split of the Nearctic (M. ochrogaster) and Holarctic (M.
      oeconomus) species, and then a subdivision of the five Palearctic species into
      two subgroups. These data support the occurrence of two European radiations, one
      North American radiation, and a later expansion of M. oeconomus from Asia to both
      Europe and North America. We further resolved the positioning of M. cabrerae as
      sister group of M. agrestis and refute the claim that M. cabrerae should be
      elevated to its own genus (Iberomys). Finally, the data support ongoing
      speciation events, especially within M. agrestis, with high levels of genetic
      divergence between the three Evolutionarily Significant Units (ESUs) previously
      identified. Similar high levels of divergence were also found among ESUs within
      M. oeconomus and M. arvalis.

PMID- 29574273
TI  - Resolving complex phylogeographic patterns in the Balkan Peninsula using closely
      related wall-lizard species as a model system.
AB  - The Balkan Peninsula constitutes a biodiversity hotspot with high levels of
      species richness and endemism. The complex geological history of the Balkans in
      conjunction with the climate evolution are hypothesized as the main drivers
      generating this biodiversity. We investigated the phylogeography, historical
      demography, and population structure of closely related wall-lizard species from
      the Balkan Peninsula and southeastern Europe to better understand diversification
      processes of species with limited dispersal ability, from Late Miocene to the
      Holocene. We used several analytical methods integrating genome-wide SNPs
      (ddRADseq), microsatellites, mitochondrial and nuclear DNA data, as well as
      species distribution modelling. Phylogenomic analysis resulted in a completely
      resolved species level phylogeny, population level analyses confirmed the
      existence of at least two cryptic evolutionary lineages and extensive within
      species genetic structuring. Divergence time estimations indicated that the
      Messinian Salinity Crisis played a key role in shaping patterns of species
      divergence, whereas intraspecific genetic structuring was mainly driven by
      Pliocene tectonic events and Quaternary climatic oscillations. The present work
      highlights the effectiveness of utilizing multiple methods and data types coupled
      with extensive geographic sampling to uncover the evolutionary processes that
      shaped the species over space and time.

PMID- 29574274
TI  - Pharmacokinetics of radiolabeled dimeric sdAbs constructs targeting human CD20.
AB  - Single-domain antibody fragments (sdAbs) are the smallest functional antigen
      binding fragments, derived from heavy chain-only camelid antibodies. When
      designed as radiolabeled monomeric probes for imaging and therapy of cancer,
      their fast and specific targeting results in high tumor-to-background ratios
      early after injection. However, their moderate absolute uptake into tumors might
      not always be sufficient to treat cancerous lesions. We have evaluated the
      pharmacokinetics of seven constructs derived from a CD20-targeting monomeric sdAb
      (alphaCD20). The constructs differed in affinity or avidity towards CD20 (dimeric
      alphaCD20-alphaCD20 and alphaCD20 fused to a non-targeting control sdAb, referred
      to as alphaCD20-ctrl) and blood half-lives (alphaCD20 fused to an albumin
      targeting sdAb (alphaAlb) = alphaCD20-alphaAlb). The constructs were radiolabeled
      with 111In (imaging) and 177Lu (therapy) using the bifunctional chelator CHX-A"
      DTPA and evaluated in vitro and in vivo. In mice, tumor uptake of 177Lu-DTPA
      alphaCD20 decreased from 4.82 +/- 1.80 to 0.13 +/- 0.05% IA/g over 72 h. Due to
      its rapid blood clearance, tumor-to-blood (T/B) ratios of >100 were obtained
      within 24 h. Although in vitro internalization indicated that dimeric 177Lu-DTPA
      alphaCD20-alphaCD20 was superior in terms of total cell-associated radioactivity,
      this was not confirmed in vivo. Blood clearance was slower and absolute tumor
      uptake became significantly higher for alphaCD20-alphaAlb. Blood levels of 177Lu
      DTPA-alphaCD20-alphaAlb decreased from 68.30 +/- 10.53 to 3.58 +/- 0.66% IA/g
      over 120 h, while tumor uptake increased from 6.21 +/- 0.94 to 24.90 +/- 2.83%
      IA/g, resulting in lower T/B ratios. Taken together, these results indicate that
      the increased size of dimeric alphaCD20-alphaCD20 or the fusion of monomeric
      alphaCD20 to an albumin-targeting moiety (alphaAlb) counterbalance their improved
      tumor targeting capacity compared to monomeric alphaCD20.

PMID- 29574275
TI  - Anti-CD73 and anti-OX40 immunotherapy coupled with a novel biocompatible enzyme
      prodrug system for the treatment of recurrent, metastatic ovarian cancer.
AB  - Approximately 75% of ovarian cancer is diagnosed once metastasis to the
      peritoneal cavity has occurred. A large proportion of patients eventually develop
      platinum-resistive tumors, which are considered terminal. In order to provide an
      alternative a novel fusion protein, mCTH-ANXA5, has been developed for the
      treatment of recurrent, metastatic ovarian cancer. The fusion protein combines
      annexin V (ANXA5), an ovarian tumor and tumor vasculature targeting protein, with
      mutated cystathionine gamma-lyase (mCTH), an enzyme that converts
      selenomethionine (SeMet) into toxic methylselenol, which generates reactive
      oxygen species and eventual tumor cell death. In order to further enhance the
      therapeutic efficacy, anti-CD73 and anti-OX40 immunostimulants were combined with
      mCTH-ANXA5, resulting in an increase of survival by 100% from 12 to 24 days post
      therapy and decrease tumor burden in mice with orthotopic metastatic ovarian
      cancer. Further evaluation of the combination therapy revealed a strong antibody
      mediated immune response, and an increased infiltration of cytotoxic T-cells
      along with a decrease in tumor promoting immune cells. This study demonstrates
      the efficacy of a synergistic, multi-drug system by attacking the tumor as well
      as enlisting the body's own defense system to treat the patient.

PMID- 29574276
TI  - CXCR4-mediated signaling regulates autophagy and influences acute myeloid
      leukemia cell survival and drug resistance.
AB  - CXCR4 surface expression is considered an independent prognostic factor for
      disease relapse and survival in acute myeloid leukemia (AML) patients. Herein, we
      investigated targetable autophagy-related mechanisms of CXCR4 for AML therapy.
      Our experiments show that activation of CXCR4 signaling in AML cells increases
      autophagic activity and decreases cytarabine-induced apoptosis. Accordingly,
      combined use of autophagy inhibitors significantly increased the sensitivity of
      AML cells to cytarabine in vitro and in vivo. Moreover, expression of autophagy
      related protein SIRT1 was correlated with SDF-1alpha-CXCR4 signaling, which
      interacts with autophagy proteins, such as ATG5 and LC3. Furthermore, in primary
      human AML samples, high CXCR4 expression was associated with elevated expression
      levels of SIRT1 and other autophagy-related proteins. Collectively, our data
      suggest new roles of SDF-1alpha-CXCR4 signaling on autophagy induction in AML
      cells, which further promoted their survival under stress. Targeting the SDF
      1alpha-CXCR4-autophagy signaling may contribute to an enhanced efficacy of active
      treatments.

PMID- 29574277
TI  - XRCC3 contributes to temozolomide resistance of glioblastoma cells by promoting
      DNA double-strand break repair.
AB  - Glioblastoma is the most frequent and aggressive form of high-grade malignant
      glioma. Due to the dismal prognosis faced by patients suffering from this
      disease, there is a need for identifying new targets that might improve therapy.
      The aim of this study was to determine the contribution of the DNA double-strand
      break (DSB) repair protein X-ray repair cross-complementing 3 (XRCC3) to the
      resistance of glioma cells to the chemotherapeutic drug temozolomide. Analysis of
      a publicly available database, E-GEOD-4290, showed that gliomas overexpress XRCC3
      (NM_005432) compared to normal brain tissue. Using an isogenic glioma cell
      system, in which XRCC3 was downregulated by interference RNA, we demonstrate that
      XRCC3 protects glioma cells against temozolomide-induced reproductive cell death,
      apoptosis and cell cycle inhibition. Furthermore, XRCC3 knockdown significantly
      reduced the rate of repair of DSBs following TMZ treatment, which results in
      increased drug sensitivity. This study confirms the importance of homologous
      recombination in the resistance of glioma cells to the methylating drug
      temozolomide and adds XRCC3 to the list of homology-directed DNA repair proteins
      as possible targets for therapeutic intervention.

PMID- 29574278
TI  - sjTREC quantification using SYBR quantitative PCR for age estimation of
      bloodstains in a Japanese population.
AB  - Individual age is a phenotypic trait that provides useful information in forensic
      investigations. Levels of signal joint T-cell receptor rearrangement excision
      circle (sjTREC) in human peripheral blood are known to decline with increasing
      age. The advantages of sjTREC quantification are the simple procedures and highly
      accurate age estimation results. Whereas TaqMan quantification PCR (qPCR) is
      widely used for sjTREC quantification, SYBR qPCR assay is not routinely used for
      evaluating ethnic data. Therefore, we focused on the advantages of the SYBR qPCR
      assay, which is cheaper and simpler to set up than the TaqMan probe assay. In
      this study, we developed a SYBR qPCR assay for sjTREC quantification from
      bloodstains from a Japanese population and evaluated the strength of correlation
      between sjTREC levels and actual age. The results were obtained from 194
      individuals ranging from 18 to 81 years old, and showed a negative correlation
      between sjTREC level and individual age (r =  -0.786). The equation for age
      estimation was Age =  -6.27 dCt (CtTBP - CtsjTREC) - 25.841 with standard error
      +/-8.0 years. Furthermore, this formula for the SYBR assay can be applied to not
      only fresh bloodstains, but also whole blood and bloodstains up to 1 month old.
      These results indicate that SYBR qPCR is an effective method for age estimation
      from bloodstains, and its practicality and affordability make it an attractive
      sjTREC quantification technique.

PMID- 29574279
TI  - Study on biocompatibility, tribological property and wear debris characterization
      of ultra-low-wear polyethylene as artificial joint materials.
AB  - Ultra-low-wear polyethylene (ULWPE) is a new type polyethylene made by experts
      who are from China petrochemical research institute, which is easy to process and
      implant. Preliminary test showed it was more resistant to wear than that of Ultra
      high-molecular weight polyethylene (UHMWPE). The purpose of the research is to
      study biocompatibility, bio-tribological properties and debris characterization
      of ULWPE. Cytotoxicity test, hemolysis test, acute/chronic toxicity and muscular
      implantation test were conducted according to national standard GB/T-16886/ISO
      10993 for evaluation requirements of medical surgical implants. We obtained that
      this novel material had good biocompatibility and biological safety. The wear
      performance of ULWPE and UHMWPE was evaluated in a pin-on-disc (POD) wear tester
      within two million cycles and a knee wear simulator within six million cycles. We
      found that the ULWPE was higher abrasion resistance than the UHMWPE, the wear
      rate of ULWPE by POD test and knee wear simulator was 0.4 mg/106cycles and (16.9
      +/- 1.8)mg/106cycles respectively, while that of UHMWPE was 1.8 mg/106cycles and
      (24.6 +/- 2.4)mg/106cycles. The morphology of wear debris is also an important
      factor to evaluate artificial joint materials, this study showed that the ULWPE
      wear debris gotten from the simulator had various different shapes, including
      spherical, block, tear, etc. The morphology of worn surface and wear debris
      analysis showed that wear mechanisms of ULWPE were adhesion wear, abrasive wear
      and fatigue wear and other wear forms, which were consistent with that of UHMWPE.
      Thus we conclude that ULWPE is expected to be a lifetime implantation of
      artificial joint.

PMID- 29574280
TI  - Glycerol-dimethacrylate as alternative hydrophilic monomer for HEMA replacement
      in simplified adhesives.
AB  - OBJECTIVES: Hydroxyethyl-methacrylate (HEMA) is still widely used in simplified
      adhesives. Indeed, several shortcomings occur with this monomer, such as water
      uptake and formation of linear polymers. This study aimed to compare the effects
      of HEMA replacement by glycerol-dimethacrylate (GDMA) on selected physicochemical
      properties and bonding performance of simplified model adhesives. MATERIALS AND
      METHODS: Experimental simplified etch-and-rinse and self-etch adhesives were
      formulated containing 20 wt% HEMA or GDMA. Three-point bending test was used to
      obtain the elastic modulus of bar-shaped specimens, and water sorption and
      solubility were attained by ISO-4049 (ISO, 2009) method. Degree of conversion was
      surveyed by Micro-Raman spectroscopy, and microtensile bond strength was tested
      after 24 h or 6 months simulated pulpal pressure aging. Statistical analysis was
      realized with two-way ANOVA and Tukey's test (p < 0.05). RESULTS: GDMA promoted
      higher elastic modulus to the self-etch adhesive, and GDMA-containing etch-and
      rinse adhesive achieved overall lower water sorption and solubility. The degree
      of conversion was statistically higher for GDMA adhesives than for HEMA etch-and
      rinse one. All bond strengths dropped significantly after aging, except that of
      GDMA self-etch adhesive. The nanoleakage was higher and gaps were found in the
      interface of HEMA-containing adhesives, which were less present in GDMA
      equivalents. CONCLUSIONS: GDMA is a feasible hydrophilic dimethacrylate monomer
      to replace HEMA in simplified adhesives, thereby providing better polymerization,
      mechanical properties and dentin adhesion as well as lower water uptake and
      solubility.

PMID- 29574281
TI  - The significance of meibomian gland changes in asymptomatic children.
AB  - PURPOSE: To evaluate meibomian gland morphology and function in children without
      ocular discomfort. METHOD: A total of 266 eyes of 266 children without signs or
      symptoms of ocular surface dysfunction were enrolled. Morphology of meibomian
      glands (MG) and non-invasive break-up time (BUT) was assessed by noncontact
      meibography. Based on lipid layer thickness (LLT) of the tear film measurements,
      66 children were chosen to be assessed by meibomian glands yielding liquid
      secretion (MGYLS). RESULTS: Based on the presence of physiologic conjunctival
      follicles (PCF), participants were divided into normal or PCF groups. The
      distortion and deficiency of MG function was significantly higher in PCF group (P
      = 0.002, 0.007, respectively). Five different gland duct shapes (vertical,
      tortuous, overriding, hooked, U-shaped) were observed. MG deficiency was
      positively correlated with age (R = 0.362, P < 0.001). Distortion and the number
      of MG showed no correlation with age (P > 0.05). However, distortion and
      deficiency of MG were negatively correlated with LLT (P < 0.001, P < 0.01).
      CONCLUSION: Children with PCF had significantly more MG distortion and deficiency
      which was associated with LLT. These results prompt future studies to determine
      if changes in MG morphology are congenital or acquired.

PMID- 29574282
TI  - The anti-inflammatory NHE-06 restores antitumor immunity by targeting NF
      kappaB/IL-6/STAT3 signaling in hepatocellular carcinoma.
AB  - The NF-kappaB/IL-6/STAT3 inflammatory axis is highly activated in a variety of
      inflammation-related cancers and contributes to suppression of antitumor
      immunity. In this study, we generated a novel herbal formula NHE-06, a water
      decocting extract from six natural herbals, Ficus carica, Taraxacum mongolicum,
      Angelica sinensis, Lonicera japonica, Pseudo-ginseng and Folium ginkgo. We
      investigated the anti-inflammatory properties of NHE-06 and its antitumor
      efficacy in hepatocellular carcinoma, a typical inflammation-related cancer. We
      found that NHE-06 effectively suppressed NF-kappaB/IL-6/STAT3 signaling and
      enhanced antitumor immunity both in vitro and in HCC-bearing mice. In a
      subcutaneous HCC mouse model, we found that NHE-06 possessed both preventive and
      therapeutic functions. Moreover, rather than the cytotoxic effects, the antitumor
      efficacy of NHE-06 was indispensable of intact immunity, since the therapeutic
      effect was only achieved in immunocompetent mice whereas failed in
      immunocompromised mice. Taken together, the novel formula of the anti
      inflammatory NHE-06 effectively restores antitumor immunosurveillance and can be
      applied for prevention and/or treatment of inflammation-related cancers.

PMID- 29574283
TI  - VS-5584 as a PI3K/mTOR inhibitor enhances apoptotic effects of subtoxic dose
      arsenic trioxide via inhibition of NF-kappaB activity in B cell precursor-acute
      lymphoblastic leukemia.
AB  - Activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway as a survival
      signaling cascade is a prominent feature of cancers such as acute lymphoblastic
      leukemia (ALL). In patients with B-cell precursor-ALL (BCP-ALL), the high
      activity of the pathway correlates with the weak response to anti-leukemic drugs
      and relapse as a result of downstream prosurvival pathway activation, such as
      nuclear factor kappa B (NF-kappaB). Recent targeted therapy (PI3K/mTOR
      inhibitors) in combination with a multifunctional conventional chemotherapeutic
      drug may be useful for treatment of BCP-ALL patients. In the current study, the
      potential of a subtoxic dose (0.2 MUM) of arsenic trioxide (ATO) in combination
      with VS-5584 (a highly potent PI3K/mTOR dual inhibitor) was tested for blocking
      of the PI3K/Akt/mTOR pathway, inhibition of NF-kappaB activation and induction of
      apoptosis and cell-cycle arrest. The data indicate that VS-5584 as a PI3K/mTOR
      inhibitor inhibited cell proliferation and induced apoptosis in NALM-6 cells by
      means of NF-kappaB transcriptional activity suppression. This apoptotic process
      markedly increased 72 h after administration of the subtoxic dose of ATO. We also
      showed that concomitant treatment of VS-5584 and the subtoxic dose of ATO
      significantly inhibited phosphorylation of NF-kappaB inhibitor alpha
      (IkappaBalpha) and S6 ribosomal protein (S6) as the downstream proteins of the
      PI3K/Akt/mTOR pathway. Combining VS-5584 and a subtoxic dose of ATO also resulted
      in down expression of the NF-kappaB target genes involved in cell proliferation
      and survival. These results indicate that incorporation of VS-5584/ATO
      combination into BCP-ALL therapeutic protocols can improve treatment and the
      survival of patients.

PMID- 29574284
TI  - Morphology, biology and phylogeny of Phalansterium arcticum sp. n. (Amoebozoa,
      Variosea), isolated from ancient Arctic permafrost.
AB  - A new species, Phalansterium arcticum sp. n., was isolated from an 8580-year-old
      Arctic permafrost layer. This organism typically lives as a sedentary
      uniflagellated cell enclosed in a thin flexible mucilaginous sheath, but can form
      naked swimming cells and amoeboid cells with eruptive pseudopodia accompanied
      with the formation of short, filopodia-like projections. In an SSU rDNA
      phylogenetic tree, it robustly groups with other species of this genus. Along
      with a description of the species, we also add new details to the description of
      the cell division of Phalansterium and the feeding process in this organism.

PMID- 29574285
TI  - Time course of reversal of valproate-mediated inhibition of lamotrigine.
AB  - PURPOSE: Conversion to lamotrigine (LTG) monotherapy from sodium valproate (VPA)
      is complicated by the robust pharmacokinetic interaction between the two AEDs.
      This study examined changes in LTG serum concentrations immediately following VPA
      discontinuation. METHODS: Ten healthy female and male adult subjects were
      initiated on LTG (Lamictal) 10 mg orally every morning for 30 days and VPA
      (Depakote ER) 500 mg orally every morning for 14 days. Morning trough (pre-dose)
      venous blood samples were obtained for determination of LTG and VPA
      concentrations on study days 14, 15, 16, 18, 20, 22, 24, 26, 28, and 30.
      Following the collection of the blood sample on day 15, VPA was discontinued.
      RESULTS: Despite stable LTG dosage serum concentrations on study day 20, 22, 24,
      26, and 28, all were significantly lower compared to baseline (p < 0.05).
      CONCLUSIONS: These observations demonstrate that the pharmacokinetic interaction
      between LTG and VPA is reversible, and that de-inhibition appears to follow a
      predictable time course. Complete offset, or reversal of this interaction takes
      place 10-14 days after VPA discontinuation. Our data also confirms the
      observation that LTG oral clearance may be inhibited by very low concentrations
      of VPA. These data support the conversion algorithm suggested by the
      manufacturer, and provide guidance to the clinician. These data provide
      clinically useful information in developing a dosing algorithm for converting
      patients to LTG monotherapy.

PMID- 29574286
TI  - Awake mastectomy under ultrasound guided thoracic paravertebral block in elderly
      patients.

PMID- 29574287
TI  - Sinus venous thrombosis following central neuraxial block: A difficult and often
      late differential diagnosis of postpartum headache.

PMID- 29574288
TI  - Comparison between ultrasound guided technique and digital palpation technique
      for radial artery cannulation in adult patients: An updated meta-analysis of
      randomized controlled trials.
AB  - STUDY OBJECTIVE: Possible advantages and risks associated with ultrasound guided
      radial artery cannulation in-comparison to digital palpation guided method in
      adult patients are not fully known. We have compared ultrasound guided radial
      artery cannulation with digital palpation technique in this meta-analysis.
      DESIGN: Meta-analysis of randomized controlled trials. SETTING: Trials conducted
      in operating room, emergency department, cardiac catheterization laboratory.
      PATIENTS: PubMed and Cochrane Central Register of Controlled Trials (CENTRAL)
      were searched (from 1946 to 20th November 2017) to identify prospective
      randomized controlled trials in adult patients. INTERVENTION: Two-dimensional
      ultrasound guided radial artery catheterization versus digital palpation guided
      radial artery cannulation. MEASUREMENTS: Overall cannulation success rate, first
      attempt success rate, time to cannulation and mean number of attempts to
      successful cannulation. Odds ratio (OR) and standardized mean difference (SMD) or
      mean difference (MD) with 95% confidence interval (CI) were calculated for
      categorical and continuous variables respectively. RESULTS: Data of 1895 patients
      from 10 studies have been included in this meta- analysis. Overall cannulation
      success rate was similar between ultrasound guided technique and digital
      palpation [OR (95% CI) 2.01 (1.00, 4.06); p = 0.05]. Ultrasound guided radial
      artery cannulation is associated with higher first attempt success rate of radial
      artery cannulation in comparison to digital palpation [OR (95% CI) 2.76 (186,
      4.10); p < 0.001]. No difference was seen in time to cannulate [SMD (95% CI) 
      0.31 (-0.65, 0.04); p = 0.30] and mean number of attempt [MD (95% CI) -0.65 (
      1.32, 0.02); p = 0.06] between USG guided technique with palpation technique.
      CONCLUSION: Radial artery cannulation by ultrasound guidance may increase the
      first attempt success rate but not the overall cannulation success when compared
      to digital palpation technique. However, results of this meta-analysis should be
      interpreted with caution due presence of heterogeneity.

PMID- 29574289
TI  - Anaesthetic challenges of Ellis-van Creveld syndrome.

PMID- 29574290
TI  - Evaluation of in-situ fatty acid extraction protocols for the analysis of
      staphylococcal cell membrane associated fatty acids by gas chromatography.
AB  - The composition and integrity of the bacterial cytoplasmic membrane is critical
      to the survival of staphylococci in dynamic environments and it is important to
      investigate how the cell membrane responds to changes in the environmental
      conditions. The staphylococcal membrane differs from eukaryotic and many other
      bacterial cell membranes by having a high abundance of branch fatty acids and
      relatively few unsaturated fatty acids. The range of available methods for
      extraction and efficient analyses of staphylococcal fatty acids was initially
      appraised to identify the best potential procedures for appraisal. Staphylococcus
      aureus subsp. aureus Rosenbach (ATCC(r) 29213) was grown under optimal conditions
      to generate a cell biomass to compare the efficiencies of three approaches to
      extract and prepare methyl esters of the membrane fatty acids: (1) acidic direct
      transesterification of lipids, (2) modified basic direct transesterification of
      membrane lipids with adjusted reaction times and temperatures, and (3) base
      catalysed hydrolysis followed by acid catalysed esterification in two separate
      chemical reactions (MIDI process). All methods were able to extract fatty acids
      from the cell mass effectively where these lipids represented approximately 5% of
      the cellular dry mass. The acidic transesterification method had the least number
      of steps, the lowest coefficient of variation at 6.7% and good resistance to
      tolerating water. Basic transesterification was the least accurate method showing
      the highest coefficient of variation (26%). The MIDI method showed good
      recoveries, but had twice the number of steps and a coefficient of variation of
      16%. It was also found that there was no need to use an anti-oxidant such as BHT
      for the protection of polyunsaturated fatty acids when the GC-MS injection liner
      was clean. It was concluded that the acidic transesterification procedures formed
      the most efficient and reproducible method for the analyses of staphylococcal
      membrane fatty acids.

PMID- 29574291
TI  - Five chambered heart: case of a huge left atrial appendage aneurysm.
AB  - Aneurysmal enlargement of the left atrial appendage is an extremely rare
      pathology and can predispose to adverse events, including cardiac arrest,
      respiratory distress, arrhythmia, heart failure, systemic thromboembolism, or
      rupture. It is usually diagnosed incidentally or after the occurrence of atrial
      tachyarrhythmias or thrombotic events in the second to fourth decades of life. We
      describe a rare case of a symptomatic giant congenital left atrial appendage
      aneurysm (LAAA) in a 26-year-old man presenting with neurologic event, in whom
      surgical resection of the aneurysm was successfully performed. This is the
      largest LAAA reported in the literature so far.

PMID- 29574292
TI  - Does health insurance coverage or improved quality protect better against out-of
      pocket payments? Experimental evidence from the Philippines.
AB  - This paper explores whether health insurance coverage or improved quality at the
      hospital level protect better against out-of-pocket payments. Using data from a
      randomized policy experiment in the Philippines, we found that interventions to
      expand insurance coverage and improve provider quality both had an impact on out
      of-pocket payments. The sample consists of 3121 child-patient patient
      observations across 30 hospitals either at baseline in 2003/04 or at the follow
      up in 2007/08. Compared to controls, interventions that expanded insurance and
      provided performance-based provider payments to improve quality both resulted in
      a decline in out-of-pocket spending (21% decline, p-value = 0.061; and 24%
      decline, p-value = 0.017, respectively). With lower out-of-pocket payments for
      hospital care, monthly household spending on personal hygiene rose by 0.9 (p
      value = 0.026) and 0.6 US$ (p-value = 0.098) under the expanded insurance and
      provider payment interventions, respectively, amounting to roughly a 40-60%
      increase relative to the controls. With the current surge for health insurance
      expansion in developing countries, our study suggests paying increased and
      possibly, equal attention to supply-side interventions will have similar impacts
      with operational simplicity and greater provider accountability.

PMID- 29574293
TI  - Inositol to aromatics -benzene free synthesis of poly oxygenated aromatics.
AB  - A method for the preparation of benzene derivatives from myo-inositol, an
      abundantly available phyto chemical is described. 1,3-Bridged acetals of inososes
      undergo step-wise elimination leading to the formation of polyoxygenated benzene
      derivatives. This aromatization reaction proceeds through the intermediacy of a
      beta-alkoxyenone, which could be isolated. This sequence of reactions starting
      from myo-inositol, provides a novel route for the preparation of polyoxygenated
      benzene derivatives including polyoxygenated biphenyl. This scheme of synthesis
      demonstrates the potential of myo-inositol as a sustainable non-petrochemical
      resource for aromatic compounds.

PMID- 29574294
TI  - Examining the utility of a train-the-trainer model for dissemination of sexual
      violence prevention in schools.
AB  - Rates of childhood sexual abuse are unacceptably high, with potentially long
      lasting consequences for those who have been victimized. Currently, there are a
      number of sexual violence prevention programs that have been developed to lower
      rates of victimization, increase awareness, and connect victims with resources.
      Within this area of research, there has been less focus on effective methods of
      program dissemination. For example, school-based sexual violence prevention
      programs have had positive outcomes; however, little is known about how these
      programs are disseminated. The train-the-trainer model of dissemination utilizes
      master trainers to equip others to implement programs, thereby allowing more
      adults to teach and subsequently more children to receive the program. This study
      used survey data from teachers and other school personnel (n = 127) to analyze
      the utility of a train-the-trainer model of dissemination for a sexual violence
      prevention program in the state of Hawai'i. Through responses of people who were
      trained to implement the program (59.8% of whom did implement), aspects of the
      training, the program itself, and factors affecting whether a person implemented
      the program were explored. Results suggest that time spent in training, job
      position, and time in that position predicted whether a person trained to
      implement the sexual violence prevention program followed through with teaching
      the program to students. Additionally, 54.7% of people who did implement the
      program had at least one student disclose sexual violence to them, indicating the
      importance of sexual violence prevention programming and dissemination of these
      programs.

PMID- 29574296
TI  - Novel prodrug PRX-P4-003, selectively activated by gut enzymes, may reduce the
      risk of iatrogenic addiction and abuse.
AB  - OBJECTIVES: Prescription stimulants are vulnerable to oral and parenteral abuse.
      Intravenous forms of abuse may be most detrimental due to an enhanced risk of
      dependence, overdose, and infectious diseases. Our objective was to discover an
      orally active prodrug of a stimulant that would not be easily converted to its
      parent when injected, thus hindering intravenous abuse. METHODS: Following an
      initial analysis of stimulant structures, the fencamfamine isomer [(-)-FCF; (N
      ethyl-3-phenylbicyclo[2.2.1]heptan-2-amine)] was chosen as a parent drug due to
      its favorable biochemical properties. Subsequently, PRX-P4-003 {(-)-N
      (Octadecanoyloxymethoxycarbonyl)-N-ethyl-3-phenylbicyclo[2.2.1]heptan-2-amine}
      qualified for further development. Experimental testing of PRX-P4-003 included
      radioligand binding assays, stability studies, and rodent pharmacokinetic and
      locomotor assays. RESULTS: Prodrug PRX-P4-003 is a pharmacologically inactive,
      hydrophobic compound, whereas its parent (-)-FCF is a dopamine reuptake inhibitor
      with weaker effects on norepinephrine reuptake (Ki = 0.07 and 0.80 MUM,
      respectively). PRX-P4-003 is metabolized to (-)-FCF in simulated intestinal fluid
      (with pancreatin) but not in simulated gastric fluid (with pepsin). Finally, PRX
      P4-003 shows a significant oral but no intravenous increase in locomotion,
      correlating with its pharmacokinetics by these different routes of
      administration. CONCLUSIONS: PRX-P4-003 is a novel prodrug stimulant
      enzymatically activated in the gut. Our data suggest a pancreatic, lipase-based
      mechanism of activation and as only 1% of this enzyme is found in the systemic
      circulation, PRX-P4-003 is unlikely to be bioactive if injected intravenously.
      Enzymatic release of (-)-FCF is needed prior to its systemic absorption, which
      may discourage oral abuse (e.g., by chewing). PRX-P4-003 is being developed for
      apathy in Alzheimer's disease and binge eating disorder.

PMID- 29574295
TI  - Self-reported neglect, amygdala volume, and symptoms of anxiety in adolescent
      boys.
AB  - Experiences of psychosocial neglect affect the developing brain and may place
      individuals at increased risk for anxiety. The majority of research in this area
      has focused on children who have experienced severe psychosocial deprivation; it
      is not clear whether typical variation in neglect experienced in community
      samples would have the same neurobiological consequences as those documented in
      extreme samples. The present study examined the associations among self-reported
      childhood neglect, amygdala volume, and anxiety symptoms in a community sample of
      138 adolescents ages 9-15 years (43% male). Linear mixed modeling yielded a three
      way interaction of neglect, sex, and brain hemisphere, reflecting a significant
      positive association between neglect and right amygdala volume in boys.
      Additional analyses indicated that right amygdala volume significantly mediated
      the association between neglect and anxiety symptoms in boys. These findings are
      consistent with previous reports of larger amygdala volumes in previously
      institutionalized children, and with documented associations between caregiving
      deprivation and anxiety symptoms. The results suggest that the effects of
      childhood neglect on limbic structures are sex-specific and lateralized, and
      provide support for a neural mechanism relating childhood neglect to later
      difficulties in emotional functioning.

PMID- 29574297
TI  - Gender differences in prevalence of psychiatric disorders, levels of alexithymia,
      and coping strategies in patients with refractory mesial temporal epilepsy and
      comorbid psychogenic nonepileptic seizures.
AB  - OBJECTIVE: The objective of this study was to investigate the psychological
      aspects and psychiatric disorders (PDs) in patients dually diagnosed with
      refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) with
      psychogenic nonepileptic seizures (PNES) treated in a tertiary center in order to
      find any gender differences in psychiatric, clinical, and sociodemographic
      characteristics. METHOD: Psychiatric assessment was performed through the
      Diagnostic and Statistical Manual for Psychiatric Disorders - 5th edition (DSM
      5). The Brazilian versions of the Medical Outcomes Study 36 (SF-36), Toronto
      Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAM-D), Hamilton Anxiety
      Scale (HAM-A), and Ways of Coping Checklist (WCC) were applied. RESULTS: Of the
      47 patients enrolled (25 females; 53.2%), females were significantly more likely
      to have a history of previous psychiatric treatment (P=0.02), family history of
      epilepsy (P=0.01), and family history of PD (P=0.03). They also presented earlier
      onset of PNES (P=0.01) and higher PNES duration (P=0.02) compared with males.
      Major depressive disorder (MDD) was the most frequent PD (24; 51.0%). Females
      presented more psychiatric diagnoses (P<0.001), more diagnoses of MDD (P<0.001),
      and posttraumatic stress disorder (PTSD) (P<0.001). Several differences regarding
      quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping
      strategies were observed between groups. CONCLUSIONS: There are significant
      gender differences in psychiatric, clinical, and sociodemographic aspects in a
      group of patients with TLE-MTS and PNES, as well as in quality of life, levels of
      alexithymia, anxiety/depressive symptoms, and coping strategies. These gender
      differences suggest that specific approaches might be adopted depending on the
      patient's gender and, consequently, their distinct psychological/psychiatric
      profile.

PMID- 29574298
TI  - The relevance of timing in nonconvulsive status epilepticus: A series of 38
      cases.
AB  - BACKGROUND: Timing in the management of nonconvulsive status epilepticus (NCSE)
      seems to be one of the most important modifiable prognostic factors. We aimed to
      determine the precise relationship between timing in NCSE management and its
      outcome. METHODS: We performed a cross-sectional study in which clinical data
      were prospectively obtained from all consecutive adults with NCSE admitted to our
      hospital from 2014 to 2016. Univariate and multivariable regression analyses were
      performed to identify clinical and timing variables associated with NCSE
      prognosis. RESULTS: Among 38 NCSE cases, 59.9% were women, and 39.5% had prior
      epilepsy history. The median time to treatment (TTT) initiation and the median
      time to assessment by a neurologist (TTN) were 5h, and the median time to first
      electroencephalography assessment was 18.5h; in the cases with out-of-hospital
      onset (n=24), the median time to hospital (TTH) arrival was 2.8h. The median time
      to NCSE control (TTC) was 16.5h, and it positively correlated with both the TTH
      (Spearman's rho: 0.439) and the TTT (Spearman's rho: 0.683). In the multivariable
      regression analyses, the TTC was extended 1.7h for each hour of hospital arrival
      delay (p=0.01) and 2.7h for each hour of treatment delay (p<0.001). Recognition
      delay was more common in the episodes with in-hospital onset, which also had
      longer TTN and TTC, and increased morbidity. CONCLUSIONS: There were pervasive
      delays in all phases of NCSE management. Delays in hospital arrival or treatment
      initiation may result in prolonged TTC. Recognition of in-hospital episodes may
      be more delayed, which may lead to poorer prognosis in these cases.

PMID- 29574299
TI  - Deep facial analysis: A new phase I epilepsy evaluation using computer vision.
AB  - Semiology observation and characterization play a major role in the presurgical
      evaluation of epilepsy. However, the interpretation of patient movements has
      subjective and intrinsic challenges. In this paper, we develop approaches to
      attempt to automatically extract and classify semiological patterns from facial
      expressions. We address limitations of existing computer-based analytical
      approaches of epilepsy monitoring, where facial movements have largely been
      ignored. This is an area that has seen limited advances in the literature.
      Inspired by recent advances in deep learning, we propose two deep learning
      models, landmark-based and region-based, to quantitatively identify changes in
      facial semiology in patients with mesial temporal lobe epilepsy (MTLE) from
      spontaneous expressions during phase I monitoring. A dataset has been collected
      from the Mater Advanced Epilepsy Unit (Brisbane, Australia) and is used to
      evaluate our proposed approach. Our experiments show that a landmark-based
      approach achieves promising results in analyzing facial semiology, where
      movements can be effectively marked and tracked when there is a frontal face on
      visualization. However, the region-based counterpart with spatiotemporal features
      achieves more accurate results when confronted with extreme head positions. A
      multifold cross-validation of the region-based approach exhibited an average test
      accuracy of 95.19% and an average AUC of 0.98 of the ROC curve. Conversely, a
      leave-one-subject-out cross-validation scheme for the same approach reveals a
      reduction in accuracy for the model as it is affected by data limitations and
      achieves an average test accuracy of 50.85%. Overall, the proposed deep learning
      models have shown promise in quantifying ictal facial movements in patients with
      MTLE. In turn, this may serve to enhance the automated presurgical epilepsy
      evaluation by allowing for standardization, mitigating bias, and assessing key
      features. The computer-aided diagnosis may help to support clinical decision
      making and prevent erroneous localization and surgery.

PMID- 29574300
TI  - People with epilepsy and their relatives want more information about risks of
      injuries and premature death.
AB  - For most people with chronic diseases such as epilepsy, thorough knowledge of the
      disease is important in order to reduce feelings of insecurity and to enable
      better management of everyday life. Whether and when to inform patients and their
      families about all the risks associated with epilepsy is a matter of controversy.
      Using a web-based survey, patients with epilepsy (PWE) (n=1183) and carers,
      family members, or guardians of PWE, who could either answer on behalf of the
      patients (CBP) (n=676) or on their own behalf (CAR) (n=231) were asked whether
      they wanted information about the risk of epilepsy-related injuries and premature
      death and also whether they had received such information. Ninety percent or more
      of PWE, CBP, and CAR reported that they wanted such information, and 50% of CAR,
      81% of CBP, and 70% of PWE had received some information about seizure-related
      injuries. Regarding risk of unexpected death, 31% of PWE, 35% of CBP, and 28% of
      CAR had received information on this issue. Those with tonic-clonic seizures were
      most eager to obtain information on these matters, and those best informed about
      epilepsy-related risks were males and the youngest part of the cohort. The wish
      for more information or the likelihood of having already received information was
      independent of the individual's seizure situation. This study demonstrates that
      there is a considerable gap between what the patients want regarding information
      and what they are actually given by healthcare providers.

PMID- 29574301
TI  - A systematic review and meta-synthesis of the impact of becoming parents on the
      couple relationship.
AB  - BACKGROUND: the transition to parenthood (TTP) is associated with changes to a
      couple's relationship. Quantitative evidence shows the TTP is associated with
      reduced satisfaction and quality of a couples' relationships. Qualitative
      research provides information on the lived experience of couples in the TTP so
      can provide a more in-depth understanding of the impact. This review therefore
      aimed to synthesise qualitative research of the perceived impact of the TTP on a
      couple's relationship in contemporary Western society. DESIGN: a systematic
      search was conducted of nine databases and grey literature. Key author, citation
      and reference searches were also undertaken. Papers were included if they
      presented qualitative data of romantic partner relationships during the TTP with
      parents aged 18 or over. Studies were restricted to those conducted from 1996 in
      Western societies. Analysis was conducted using meta-ethnography. FINDINGS:
      searches identified 5256 papers. After applying inclusion criteria 12 papers were
      included in the meta-synthesis. Six main themes were identified: (1) Adjustment
      Phase (a period of change in the relationship), (2) Focus on the Baby (with a sub
      theme of feeling unprepared for the relationship impact), (3) Communication
      (shifts in communication patterns and importance), (4) Intimacy (changes to
      sexual relations, romance and closeness), (5) Strain on the Relationship (short
      term or prolonged), and (6) Strengthened Relationships (deepening of connection
      and new affinity). Except for the themes of Strain on the Relationship and
      Strengthened Relationships, the findings showed the TTP had positive and negative
      impacts on couples' relationships. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      the review highlights a range of TTP relationship issues that couples experience
      and may require help with. Health care professionals working with parents in the
      TTP may be able to provide support through antenatal education that includes
      preparation for relationship changes, and provision of postnatal support to
      identify and overcome problems.

PMID- 29574302
TI  - Application of alpha- and beta-naphthoflavones as monooxygenase inhibitors of
      Absidia coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium sp. KCh
      6651 in transformation of 17alpha-methyltestosterone.
AB  - In this work, 17alpha-methyltestosterone was effectively hydroxylated by Absidia
      coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium sp. KCh 6651.
      A. coerulea KCh 93 afforded 6beta-, 12beta-, 7alpha-, 11alpha-, 15alpha-hydroxy
      derivatives with 44%, 29%, 6%, 5% and 9% yields, respectively. S. racemosum KCh
      105 afforded 7alpha-, 15alpha- and 11alpha-hydroxy derivatives with yields of
      45%, 19% and 17%, respectively. Chaetomium sp. KCh 6651 afforded 15alpha-,
      11alpha-, 7alpha-, 6beta-, 9alpha-, 14alpha-hydroxy and 6beta,14alpha-dihydroxy
      derivatives with yields of 31%, 20%, 16%, 7%, 5%, 7% and 4%, respectively.
      14alpha-Hydroxy and 6beta,14alpha-dihydroxy derivatives were determined as new
      compounds. Effect of various sources of nitrogen and carbon in the media on
      biotransformations were tested, however did not affect the degree of substrate
      conversion or the composition of the products formed. The addition of alpha- or
      beta-naphthoflavones inhibited 17alpha-methyltestosterone hydroxylation but did
      not change the percentage composition of the resulting products.

PMID- 29574303
TI  - Prevalence and correlates of antipsychotic polypharmacy in Hong Kong.
AB  - BACKGROUND: Antipsychotic polypharmacy (APP) remains a common practice despite
      inconclusive empirical evidence of additional efficacy and potential exacerbation
      of side effects. Previous studies suggest APP rate is notably high in East Asia.
      This paper aims to investigate the prevalence and correlates of APP in Hong Kong.
      METHOD: This was a cross-sectional study of 728 patients with psychosis. The
      demographics and clinical information, including age, gender, diagnosis,
      hospitalization history, and medication were collected. Chi-square tests and
      logistic regression analyses were used to study correlates of APP. RESULTS: The
      APP rate for psychosis was 24.2% (n = 728) and that for schizophrenia was 26.0%
      (n = 611), both considerably lower than our previous local data and that from
      East Asian regions. The most widely used APP prescription fell within the
      atypical/atypical combination (i.e., Amisulpride/Clozapine and
      Paliperidone/Olanzapine), and Olanzapine was the most commonly prescribed
      antipsychotic. At least 75% of APP patients with psychosis took at least one type
      of atypical antipsychotics in their medical regimen. Typical/typical polypharmacy
      was associated with older age and use of antiparkinson drugs. Typical/atypical
      polypharmacy was associated with the use of antiparkinson drugs and anxiolytics,
      as well as inpatient status. Atypical/atypical polypharmacy was associated with
      younger age, inpatient status, and the use of mood stabilizers. CONCLUSION:
      Overall, our study highlights a relatively low APP rate in Hong Kong when
      compared to other countries in East Asia. Age, inpatient status and use of
      antiparkinson drugs, anxiolytics and mood stabilizers were associated with use of
      APP.

PMID- 29574304
TI  - An in vitro study on noradrenergic modulation of final oocyte maturation in the
      catfish Heteropneustes fossilis.
AB  - This study was aimed to elucidate in vitro the effects of endogenous
      catecholamines: dopamine (DA), noradrenaline (NA) and adrenaline (A), and the
      beta-adrenergic blocker propranolol on induction of final oocyte maturation (FOM)
      in the catfish Heteropneustes fossilis. With this aim, post vitellogenic
      follicles from sexually mature gravid female catfish were incubated with each of
      DA, NA and A in a concentration range of 5-250 MUM, and propranolol in a
      concentration range of 1-200 MUg/mL at time points varying from 0 to 30 h).
      Translucent follicles without germinal vesicle (GV) and opaque follicles with GV
      were scored separately for the calculation of percentage germinal vesicle
      breakdown (GVBD), an index of FOM. Data were analyzed by one-way ANOVA and were
      considered statistically significant when P values were less than 0.05. The
      analysis of the data showed that the incubation with NA only stimulated GVBD in a
      concentration - and time-dependent manner. Though the incubation with propranolol
      decreased total follicular cAMP level significantly at and above 10 MUg/mL
      concentrations, a significant effect of the GVBD increase was noticed at 50
      MUg/mL or higher. However, the 10 MUg/mL concentration of propranolol was
      effective to inhibit the NA-induced GVBD significantly albeit at a low level
      (39%). The present study suggests that final oocyte maturation is modulated by NA
      through a beta-adrenergic mechanism, implicating a neural control of oocyte
      maturation and ovulation in teleosts.

PMID- 29574305
TI  - Proliferative and apoptotic changes in the healthy canine endometrium and in
      cystic endometrial hyperplasia.
AB  - Proliferation and apoptosis play an important role in cyclic changes in the
      healthy canine endometrium. Proteins of the Bcl-2-family are known to be involved
      in the regulation of apoptosis. However, only few reports mention their
      expression patterns during cystic endometrial hyperplasia (CEH). In order to
      correlate proliferative and apoptotic processes, expression of the apoptosis
      regulatory proteins Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) in healthy and
      cystic hyperplastic endometrial tissue as well as in pyometra was investigated.
      Uteri from 33 bitches were assigned to three groups: group 1 - healthy
      endometrium (n = 12), group 2 - CEH (n = 17) and group 3 - pyometra (n = 4).
      Markers for proliferation (Ki-67) and apoptosis (activated caspase-3 and TUNEL
      method) as well as expression of Bcl-2 and Bax were determined in all endometrial
      layers. For groups 1 and 2 this was done during endometrial gland secretion in
      mid and late luteal phase (mLP, lLP), endometrial reparation in early anestrus
      (eAE) and in the regenerated endometrium in late anestrus (lAE). For group 3 only
      the late luteal phase was investigated. In group 1, cyclic proliferation patterns
      were found predominantly in superficial glands (SG) and stroma, whereas
      progesterone-mediated low expression levels coincided with high apoptosis rates
      in the basal glands (BG). In eAE, higher apoptotic activity was detected compared
      to lLP and lAE. Bcl-2 and Bax expression levels showed an inverse cyclic
      relationship in all tissue layers. In the stroma, in eAE, a rise in proliferative
      activity and concomitant increase in anti-apoptotic Bcl-2 expression levels was
      found, indicating that this layer serves as a source for endometrial
      regeneration. In CEH, no or limited cyclic patterns of proliferation, apoptosis,
      Bcl-2 and Bax were found. Increased proliferation rates coincided with
      deregulated apoptosis. Besides the glandular compartments, the stroma played an
      important role in the pathogenesis of canine CEH. In case of pyometra, both
      proliferation and apoptosis increased, indicating irreversible damage of the
      inflamed canine endometrium. In conclusion Bcl-2 and Bax play a role both in the
      physiological regenerative processes of the cyclic canine endometrium and in
      deregulating proliferation and apoptosis in CEH and pyometra.

PMID- 29574306
TI  - Quantifying known and emerging uterine pathogens, and evaluating their
      association with metritis and fever in dairy cows.
AB  - Metritis is caused by polymicrobial infection; however, recent metagenomic work
      challenges the importance of known pathogens such as Escherichia coli and
      Trueperella pyogenes while identifying potential new pathogens such as
      Bacteroides pyogenes, Porphyromonas levii and Helcococcus ovis. This study aims
      to quantify known and emerging uterine pathogens, and to evaluate their
      association with metritis and fever in dairy cows. Metritis was diagnosed at 6 +/
      2 days postpartum, a uterine swab was collected and rectal temperature was
      measured. 39 cows were classified into three groups: Healthy (n = 14), Metritis
      without fever (MNoFever; n = 12), and Metritis with fever (MFever; n = 13).
      Absolute copy number was determined for total bacteria and for 8 potentially
      pathogenic bacteria using droplet digital PCR. Both MNoFever and MFever cows had
      higher copy number of total bacteria, Fusobacterium necrophorum, Prevotella
      melaninogenica, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis
      than Healthy cows. MNoFever and MFever groups were similar. There was no
      difference among groups in copy number of Escherichia coli, Trueperella pyogenes,
      and Bacteroides heparinolyticus, and they all had low copy numbers. Our work
      confirms the importance of some bacteria identified by culture-based studies in
      the pathogenesis of metritis such as Fusobacterium necrophorum and Prevotella
      melaninogenica; however, it challenges the importance of others such as
      Escherichia coli and Trueperella pyogenes at the time of metritis diagnosis.
      Additionally, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis
      were recognized as emerging pathogens involved in the etiology of metritis.
      Furthermore, fever was not associated with the total bacterial load or specific
      bacteria.

PMID- 29574307
TI  - Immunocastration of goats using anti-gonadotrophin releasing hormone vaccine.
AB  - The aim of this study was to evaluate the immuno-sterilizing action of anti
      gonadotrophin-releasing hormone (anti-GnRH) vaccine in goats. Eighteen male goats
      were randomly distributed to receive three treatments: T1 (control) - whole
      animals, and T2 and T3 - application of 0.5 and 1.0 mL of anti-GnRH vaccine,
      respectively, with six replicates and one goat per experimental unit. Vaccine was
      administered at 8 months of age and 30 days after the first immunization.
      Testicular biometry was evaluated monthly, along with seminal collections, for
      the physical and morphological evaluation of semen. At the time of slaughter, the
      testicle were collected, and fragments were measured and removed for histological
      evaluation. The data were evaluated for normality by the Shapiro-Wilk test,
      followed by appropriate statistical tests for each variable. A reduction in width
      and length of the right and left testicles was observed and, consequently, the
      scrotal circumference of the immunized animals reduced after the second vaccine
      application (P < 0.05). Thirty-days after the first vaccine application, there
      was a negative effect on seminal production and quality; and 60 days after the
      second application, a pronounced reduction was observed in all seminal parameters
      in the vaccinated animals, including azoospermia (83.33% of animals; P < 0.05).
      Vaccine application reduced testicular weight, seminiferous tubule diameter, and
      gonadosomatic and tubulosomatic index (P < 0.05), but did not influence the
      proportion of testicular parenchyma components (P > 0.05). Two applications of
      the anti-GnRH conjugate are effective for the immunological castration of goats,
      and the 0.5 mL dose is recommended for use in crossbred goats.

PMID- 29574308
TI  - The influence of hypoxia and IFN-gamma on the proteome and metabolome of
      therapeutic mesenchymal stem cells.
AB  - Over the past 15 years, mesenchymal stem cells (MSCs) have been assessed for
      their capacity to suppress inflammation and promote tissue repair. Regardless of
      whether the cells are primed (exposed to instructive cues) before administration,
      their phenotype will respond to environmental signals present in the
      pathophysiological setting being treated. Since hypoxia and inflammation coexist
      in the settings of acute injury and chronic disease we sought to explore how the
      proteome and metabolome of MSCs changes when cells were exposed to 48 h of 1%
      oxygen, interferon gamma (IFN-gamma), or both cues together. We specifically
      focused on changes in cell metabolism, immune modulation, extracellular matrix
      secretion and modification, and survival capacity. IFN-gamma promoted expression
      of anti-pathogenic proteins and induced MSCs to limit inflammation and fibrosis
      while promoting their own survival. Hypoxia instead led to cell adaptation to low
      oxygen, including upregulation of proteins involved in anaerobic metabolism,
      autophagy, angiogenesis, and cell migration. While dual priming resulted in
      additive effects, we also found many instances of synergy. These data lend
      insight to how MSCs may behave after administration to a patient and suggest how
      priming cells beforehand could improve their therapeutic capacity.

PMID- 29574309
TI  - Vehicle manoeuvers as surrogate safety measures: Extracting data from the gps
      enabled smartphones of regular drivers.
AB  - Network screening is a key element in identifying and prioritizing hazardous
      sites for engineering treatment. Traditional screening methods have used observed
      crash frequency or severity ranking criteria and statistical modelling
      approaches, despite the fact that crash-based methods are reactive.
      Alternatively, surrogate safety measures (SSMs) have become popular, making use
      of new data sources including video and, more rarely, GPS data. The purpose of
      this study is to examine vehicle manoeuvres of braking and accelerating extracted
      from a large quantity of GPS data collected using the smartphones of regular
      drivers, and to explore their potential as SSMs through correlation with
      historical collision frequency and severity across different facility types. GPS
      travel data was collected in Quebec City, Canada in 2014. The sample for this
      study contained over 4000 drivers and 21,000 trips. Hard braking (HBEs) and
      accelerating events (HAEs) were extracted and compared to historical crash data
      using Spearman's correlation coefficient and pairwise Kolmogorov-Smirnov tests.
      Both manoeuvres were shown to be positively correlated with crash frequency at
      the link and intersection levels, though correlations were much stronger when
      considering intersections. Locations with more braking and accelerating also tend
      to have more collisions. Concerning severity, higher numbers of vehicle
      manoeuvres were also related to increased collision severity, though this
      relationship was not always statistically significant. The inclusion of severity
      testing, which is an independent dimension of safety, represents a substantial
      contribution to the existing literature. Future work will focus on developing a
      network screening model that incorporates these SSMs.

PMID- 29574310
TI  - High serum IGF-1 levels are associated with pregnancy loss following frozen
      thawed euploid embryo transfer cycles.
AB  - An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been
      shown to exert detrimental effects of embryo development possibly leading to an
      increase in pregnancy loss. Interestingly, the administration of somatostatin to
      rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and
      thus reversed its deleterious effects on embryo development and increased the
      number of normal embryos. Therefore, we investigated whether serum levels of IGF
      1 correlate with the incidence of pregnancy loss following IVF. To account for
      aneuploidy and the effect of hormonal supplementation on serum IGF levels, we
      only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera
      collected in the follicular phase (cycle day 10) were tested for levels of IGF-1,
      IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of
      156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a
      first trimester pregnancy loss. Women with a pregnancy loss had significantly
      higher serum IGF-1 levels compared to those who achieved a live birth (18.0 +/-
      1.1 vs. 14.6 +/- 0.7 ng/mL, respectively). The two groups had comparable serum
      IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age,
      body mass index, gravidity, parity, number of prior miscarriages, peak
      endometrial thickness, or infertility diagnosis between the two groups. In
      conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF
      1 concentrations may be at increased risk of pregnancy loss. This may constitute
      a novel molecular explanation of pregnancy loss of euploid conceptus.

PMID- 29574311
TI  - Fabrication of CDs/CdS-TiO2 ternary nano-composites for photocatalytic
      degradation of benzene and toluene under visible light irradiation.
AB  - An efficient cadmium sulfide quantum-dots (CdS QDs) and carbon dots (CDs)
      modified TiO2 photocatalyst (CdS/CDs-TiO2) was successfully fabricated. The as
      prepared ternary nano-composites simultaneously improved the photo-corrosion of
      CdS and amplified its photocatalytic activity. The introduction of CdS QDs and
      CDs could enhance more absorbance of light, prevent the undesirable electron/hole
      recombination, and promote charge separation, which was important for the
      continuous formation of OH and O2- radicals. When the optimal mass ratio of CdS
      QDs to CDs was 3:1, above 90% degradation efficiencies were achieved for benzene
      within 1h and toluene in 2h, while that of pure TiO2 (P25), CdS QDs-TiO2, CDs
      TiO2 nano-composites was around 15%. Owing to the symmetric structure and
      conjugation of methyl with benzene ring, the degradation of toluene was more
      difficult than benzene to carry on. The new fabricated nano-composites showed
      good prospective application of cleaning up refractory pollutants and the
      resource utilization.

PMID- 29574312
TI  - Solvo-thermal synthesis of a unique alkaline earth-transition Ba-Cd micro-porous
      coordination framework as hetero-metallic luminescent sensor for Cu2+ and real
      time detection of benzaldehyde.
AB  - In this work a unique hetero-metallic alkaline earth-transition Ba-Cd luminescent
      micro-porous metal-organic framework {[BaCd(MU6-tp)1.5(MU2-Cl)(H2O)
      (DMF)2].0.75H2O}n (H2tp=terephthalic acid) (1) has been prepared under solvo
      thermal conditions. In 1 infinite 1D {Ba-X-Cd} (X=O, Cl) inorganic chains are
      linked via these full de-pronated tp2- ligands forming a unique 3D I1O2 type
      micro-porous coordination framework. PXRD patterns of 1 have been determined
      confirming pure phases of 1. Luminescence investigations suggested that 1
      exhibits highly selective and sensitive sensing for trace amounts of benzaldehyde
      in ethanol, which provides a facile method for real-time detection of
      benzaldehyde. Meanwhile 1 also exhibits highly selective and sensitive sensing
      for Cu2+ over other cations with high quenching efficiency Ksv value
      1.15*104L.mol-1. As far as we know, 1 represents the first example of alkaline
      earth-transition hetero-metallic Ba-Cd micro-porous coordination framework as bi
      functional luminescent probes for Cu2+ and benzaldehyde.

PMID- 29574313
TI  - Comparison between coagulation-flocculation and ozone-flotation for Scenedesmus
      microalgal biomolecule recovery and nutrient removal from wastewater in a high
      rate algal pond.
AB  - The removal of nutrients by Scenedesmus sp. in a high-rate algal pond, and
      subsequent algal separation by coagulation-flocculation or flotation with ozone
      to recover biomolecules, were evaluated. Cultivation of Scenedesmus sp. in
      wastewater resulted in complete NH3-H removal, plus 93% total nitrogen and 61%
      orthophosphate removals. Ozone-flotation obtained better water quality results
      than coagulation-flocculation for most parameters (NH3-N, NTK, nitrate and
      nitrite) except orthophosphate. Ozone-flotation, also produced the highest
      recovery of lipids, carbohydrates and proteins which were 0.32 +/- 0.03, 0.33 +/-
      0.025 and 0.58 +/- 0.014 mg/mg of biomass, respectively. In contrast, there was a
      low lipid extraction of 0.21 mg of lipids/mg of biomass and 0.12-0.23 mg of
      protein/mg of biomass in the coagulation-flocculation process. In terms of
      biomolecule recovery and water quality, ozone showed better results than
      coagulation-flocculation.

PMID- 29574314
TI  - Correlation between pyrolysis behaviors of the components and the overall
      pyrolysates from pulping spent liquor.
AB  - The pyrolysis behaviors of the three major organic components of eucalyptus
      alkaline peroxide mechanical pulping (APMP) spent liquor including alkali lignin
      (AL), lignin-carbohydrate complexes (LCC), and polysaccharide (PLS) were studied
      with emphasis on the effect and contributions of components on the overall
      pyrolysates of APMP spent liquor solid (ASLS). Profound differences on product
      properties from each component pyrolysis were illustrated. The results indicated
      that the bio-oil during ASLS pyrolysis was mainly attributed to AL, while the bio
      gas and char were mostly affected by PLS. Small molecule hydrocarbons released
      during ASLS pyrolysis mainly came from AL and LCC, and CO and CO2 mainly produced
      from PLS. As for bio-oils, AL generated the largest proportion of monomeric
      phenols and aromatic hydrocarbons (AHs), while PLS and LCC mainly contributed to
      the production of ketones, furans and acids. The correlation shown here is of
      interest for further studies on pulping spent liquor grading utilization.

PMID- 29574315
TI  - Application of alpha-amylase as a novel biodemulsifier for destabilizing
      amphiphilic polymer-flooding produced liquid treatment.
AB  - The performance and de-emulsification mechanism of alpha-amylase, a novel
      environmental friendly biodemulsifier in petroleum industry, was investigated at
      room temperature. The effects of alpha-amylase on the viscosity of amphiphilic
      polymer solution and de-emulsification rate were studied by changing the
      concentration of alpha-amylase, temperature and salinity. Polymer molecular
      weight, Zeta potential, interfacial film strength and interfacial tension were
      measured to investigate the de-emulsification mechanism of alpha-amylase. The
      results show that alpha-amylase is an efficient biodemulsifier to increase the de
      emulsification rate of amphiphilic polymer emulsions. Hydrolysis of alpha-amylase
      to amphiphilic polymers destroys the structure of the amphiphilic polymer,
      thereby reduces the viscosity and the interfacial film strength of the system.
      Once de-emulsification is completed, the lower layer, i.e. the emulsified layer,
      will be clear. Thus, alpha-amylase can be applied as an effective de-emulsifier
      for amphiphilic polymer-stabilized O/W emulsion.

PMID- 29574316
TI  - Enhancing the robustness of microbial fuel cell sensor for continuous copper(II)
      detection against organic strength fluctuations by acetate and glucose addition.
AB  - Microbial fuel cell sensors have shown great promise for continuous monitoring of
      toxic substances in wastewater, but a persistent problem is the signal
      interferences due to fluctuations in organic strength. An approach to eliminate
      the interferences is to saturate the sensor with an added organic substrate. In
      this study, signal stabilization using acetate and glucose addition (150, 300 and
      500 mg COD/L) to domestic wastewater was examined. Addition of acetate (500 mg
      COD/L) gave the best performance, increasing the robustness of the sensor by
      reducing signal interference (decrease in baseline current) from 65% to 15% for a
      sudden 75% decrease in organic strength. The sensor sensitivity remained
      unchanged at current drop of 0.16%/(mg/L Cu(II)) for a toxicity event (300 mg/L
      Cu(II)). Addition of acetate (300 mg COD/L) and glucose (150, 300 and 500 mg
      COD/L) also resulted in increased robustness but led to a reduced sensitivity to
      Cu(II).

PMID- 29574317
TI  - Enhancement of TCE removal by a static magnetic field in a fungal biotrickling
      filter.
AB  - A fungal biotrickling filter (BTF) was employed to treat trichloroethylene (TCE)
      gas under different magnetic field intensities (MFIs). When the TCE inlet
      concentrations were approximately 370, 500-900, and 1000 mg/m3, the removal
      performances followed the order: MFI 20.0 mT > MFI 60.0 mT > MFI 80.0 mT > MFI 0
      mT. In particular, at a TCE inlet concentration of 1000 mg/m3, MFI 20.0 mT was
      significantly better than MFI 0 mT performance. The corresponding removal
      efficiencies and maximum elimination capacities were 52.9%, 4854.1 mg/m3 h and
      39.4%, 3594.8 mg/m3 h, respectively. BTF was shut down completely for 7 days and
      rapidly recovered in 6-10 days. High-throughput sequencing indicated that MF
      significantly affected the fungal community and significantly improved the
      relative abundance of the phylum Ascomycota, achieving the highest abundance of
      Ascomycota at MFI 20.0. These results indicated that a lower MFI can efficiently
      improve TCE removal performance in a fungal BTF.

PMID- 29574318
TI  - R1 dispersion contrast at high field with fast field-cycling MRI.
AB  - Contrast agents with a strong R1 dispersion have been shown to be effective in
      generating target-specific contrast in MRI. The utilization of this R1 field
      dependence requires the adaptation of an MRI scanner for fast field-cycling
      (FFC). Here, we present the first implementation and validation of FFC-MRI at a
      clinical field strength of 3 T. A field-cycling range of +/-100 mT around the
      nominal B0 field was realized by inserting an additional insert coil into an
      otherwise conventional MRI system. System validation was successfully performed
      with selected iron oxide magnetic nanoparticles and comparison to FFC-NMR
      relaxometry measurements. Furthermore, we show proof-of-principle R1 dispersion
      imaging and demonstrate the capability of generating R1 dispersion contrast at
      high field with suppressed background signal. With the presented ready-to-use
      hardware setup it is possible to investigate MRI contrast agents with a strong R1
      dispersion at a field strength of 3 T.

PMID- 29574319
TI  - Nutrient enrichment during shrimp cultivation alters bacterioplankton assemblies
      and destroys community stability.
AB  - Intensive shrimp farming is generally accompanied by nutrient enrichment and
      gradual eutrophication, which impose major threats to shrimp culture ecosystems.
      However, little is known about how the bacterioplankton community in a rearing
      environment responds to increased eutrophication during shrimp culture processes.
      In this study, we used the MiSeq sequencing technique to explore the impacts of
      nutrient enrichment on the assembly and stability of the bacterioplankton
      community. Our results showed that magnitudes of the changes in the
      bacterioplankton community compositions (BCCs) and diversity were closely
      associated with eutrophication level. Moreover, a phylogenetic-based mean nearest
      taxon distance (MNTD) analysis revealed that increased eutrophication
      significantly (P < 0.01) changed the bacterioplankton ecological processes from
      deterministic to stochastic. A structural equation model showed that
      eutrophication indicators affected the BCCs either directly by controlling
      resources or indirectly by modifying other environmental variables of the shrimp
      ponds in complex pathways. Furthermore, association network comparisons revealed
      that nutrient enrichment increased the complexity of interspecies interactions
      and the proportion of cooperative interactions and decreased the proportion of
      generalists, which suggest that nutrient enrichment destroyed the community
      stability. These findings suggest that minimizing nutrient pollution, especially
      at the end of cultivation, could be an important management tool for establishing
      a microbially mature water system.

PMID- 29574320
TI  - Sulfate facilitates cadmium accumulation in leaves of Vicia faba L. at flowering
      stage.
AB  - Cadmium (Cd) is a toxic element, and is prevalent all over the world because of
      industrialization, mining, sewage sludge, or pesticide supply. Sulfur deficiency
      is also a frequent problem faced in agriculture. To date, information relating to
      effects of sulfate on Cd toxicity is still limited. To elucidate how sulfate
      affects Cd accumulation in faba bean, subcellular accumulation of Cd in leaves
      consisting of apoplastic washing fluid, symplastic fluid and the cell wall under
      deficient, sufficient and excess sulfate treatments were investigated in the
      present study. By using stable isotope of Cd (106Cd), we also traced Cd
      accumulation in young leaves at flowering stage from early and newly uptake of Cd
      in the same plants as affected by sulfate. We found that excess sulfate supply
      significantly increased newly uptake of Cd without affecting early uptake of Cd
      when compared with sufficient sulfate treatment, which resulted in enhanced total
      Cd in leaves by excess sulfate. Since newly uptake of Cd in leaves was from root
      uptake directly, we conclude that excess sulfate supply enhanced Cd originated
      from root uptake directly rather than re-translocation from old leaves, which is
      related to increased Cd accumulation in young leaves of faba bean. Subcellular
      analysis showed that the enhanced Cd by excess sulfate addition was a consequence
      of enhanced Cd in cell walls, while Cd accumulation in the apoplastic washing
      fluid and symplastic fluid were unchanged. The increased Cd by excess sulfate
      supply might be related to increased proportion of Cd speciation CdSO40 in the
      growth medium because of faster diffusion of CdSO40 than Cd2+. To test whether
      macronutrients, micronutrients, sulfate and non-protein thiol involved in cell
      wall-Cd accumulation as affected by sulfate, correlations of subcellular Cd with
      subcellular macronutrients, micronutrients, sulfate, and non-protein thiol were
      analyzed. We found that cell wall-Cd was negatively correlated with K and Ca
      concentrations, whereas cell wall-Cd was positively correlated with Cu and
      symplastic non-protein thiol concentrations. However, when compared with
      sufficient sulfate, excess sulfate decreased K concentration and increased
      symplastic non-protein thiol concentration without changing Ca and Cu
      concentrations. Based on those results, reduction of K concentration and
      enhancement of symplastic non-protein thiol concentration by sulfate supply might
      be a reason for increase of cell wall-Cd concentration. Taken together, increased
      Cd in cell walls of leaves by sulfate supply contributes to enhance Cd
      accumulation.

PMID- 29574321
TI  - Gold nanoparticles/4-aminothiophenol interfaces for direct electron transfer of
      horseradish peroxidase: Enzymatic orientation and modulation of sensitivity
      towards hydrogen peroxide detection.
AB  - Hydrogen peroxide electrochemical detection by horseradish peroxidase has been
      widely studied. The use of gold nanoparticles to prepare electrode/enzyme
      bioconjugates has attracted attention due to their catalytic properties. In this
      work, it is reported the use of gold nanoparticles and 4-aminothiophenol as a
      scaffold to obtain a suitable matrix for enzyme bioconjugation with horseradish
      peroxidase. A critical factor in biosensors design and development is the
      enzymatic electrochemical activity understanding. Comparison of voltammetric
      studies of the heme prosthetic group showed a reversible electrochemical behavior
      when the enzymes were immobilized in a well-dispersed gold deposit; on the other
      hand, a discrete redox response was observed on a randomly deposited gold
      electrode. These results show that the distance between enzymes is essential.
      Hydrogen peroxide catalysis and the enzymatic behavior were analyzed considering
      two types of nanoparticles dispositions. The catalytic behavior observed in the
      well-dispersed nanoparticles configuration suggests a preserved enzyme folding, a
      decrease of steric impediments, and appears to be a better immobilization
      strategy. In contrast, the randomly electrodeposited gold electrode decreased the
      enzyme orientation and the electrochemical activity. The advantages of this
      methodology are the electrode fabrication affordable cost and the enzymatic
      direct electron transfer response improvement.

PMID- 29574322
TI  - Expressional changes in stemness markers post electrochemotherapy in pancreatic
      cancer cells.
AB  - Pancreatic cancer is one of the most lethal cancers with high metastatic
      potential and strong chemoresistance. The capability of a tumor to grow and
      propagate is dependent on a small subset of cells within a tumor, termed cancer
      stem cells. Cancer stem cells exhibit great tumorigenicity and are closely
      correlated with drug resistance and tumor recurrence. The aim of our study was to
      illustrate electrochemotherapy as an effective treatment for pancreatic cancer
      along with the expression change in stemness genes (Nanog, Sox2 and Oct3/4) in
      pancreatic cancer cells post electrochemotherapy with bleomycin, cisplatin and
      oxaliplatin. Our results showed the enhanced expression of Nanog and decreased
      expression level of Oct3/4 after electrochemotherpy. We thus propose that these
      stemness markerS may have important roles in the initiation and/or recurrence of
      pancreatic cancer, and consequently may serve as important molecular diagnostics
      and/or therapeutic targets for the development of novel treatment strategies in
      pancreatic cancer patients. In conclusion, targeting these stemness factors could
      potentially improve electrochemotherapy as a treatment and preventing recurrence.

PMID- 29574323
TI  - Deep insights into the mode of ATP-binding mechanism in Zebrafish cyclin
      dependent protein kinase-like 1 (zCDKL1): A molecular dynamics approach.
AB  - In eukaryotes, the serine/threonine kinases (STKs) belonging to cyclin-dependent
      protein kinases (CDKs) play significant role in control of cell division and curb
      transcription in response to several extra and intra-cellular signals
      indispensable for enzymatic activity. The zebrafish cyclin-dependent protein
      kinase-like 1 protein (zCDKL1) shares a high degree of sequence and structural
      similarity with mammalian orthologs and express in brain, ovary, testis, and low
      levels in other tissues. Regardless of its importance in the developmental
      process, the structure, function and mode of ATP recognition have not been
      investigated yet due to lack of experimental data. Henceforth, to gain atomistic
      insights in to the structural dynamics and mode of ATP binding, a series of
      computational techniques involving theoretical modeling, docking, molecular
      dynamics (MD) simulations and MM/PBSA binding free energies were employed. The
      modeled bi-lobed zCDKL1 shares a high degree of secondary structure topology with
      human orthologs where ATP prefers to lie in the central cavity of the bi-lobed
      catalytic domain enclosed by strong hydrogen bonding, electrostatic and
      hydrophobic contacts. Long range MD simulation portrayed that catalytic domain of
      zCDKL1 to be highly rigid in nature as compared to the complex (zCDKL1-ATP) form.
      Comparative analysis with its orthologs revealed that conserved amino acids i.e.,
      Ile10, Gly11, Glu12, Val18, Arg31, Phe80, Glu 130, Cys143 and Asp144 were crucial
      for ATP binding mechanism, which needs further investigation for legitimacy.
      MM/PBSA method revealed that van der Waals, electrostatic and polar solvation
      energy mostly contributes towards negative free energy. The implications of ATP
      binding mechanism inferred through these structural bioinformatics approaches
      will help in understanding the catalytic mechanisms of important STKs in
      eukaryotic system.

PMID- 29574324
TI  - Transcript analyses of ethylene pathway genes during ripening of Chinese jujube
      fruit.
AB  - The fruit of Chinese jujube (Ziziphus jujuba Mill.) is immensely popular
      worldwide, while its fleshy fruit has a very short shelf life and suffers serious
      postharvest damage. The fruit has been controversially classified as non
      climacteric, though the mechanisms underlying its ripening behavior, particularly
      the role of ethylene, have remained unclear. In this study, low and stable
      ethylene production was detected during ripening of Z. jujuba 'Dongzao' fruit,
      with production increasing at the full maturity stage. To determine potential
      ripening behavior, the fruit of five cultivars were harvested at the white mature
      stage, and all exhibited a first decreasing and then moderately increasing
      respiration rate without concomitant climacteric-like ethylene production during
      shelf storage. Treatment with 1.0 MUL L-1 1-methylcyclopropene (1-MCP) inhibited
      respiration and ethylene production in white mature fruit, though the effects of
      100 MUL L-1 exogenous ethylene were not significant. The transcript levels of
      genes involved in ethylene biosynthesis, perception, and signal transduction were
      not elevated during fruit-ripening onset but substantially increased at the full
      red ripening stage. Moreover, expression of genes controlling ethylene
      biosynthesis and perception mainly occurred in an auto-inhibited System-1-like
      manner, but signaling pathway genes were minimally affected by exogenous ethylene
      or 1-MCP. These results show that the ripening of Chinese jujube is non
      climacteric. The basal level of ethylene likely plays a minor role in ripening
      regulation but is necessary to maintain normal ripening. This study elucidates
      the effects of ethylene on jujube fruit ripening, characterizing the ripening of
      this fruit as non-climacteric, and also provides strategies for the improvement
      and maintenance of fruit quality and the extension of shelf life during
      postharvest storage.

PMID- 29574325
TI  - A disturbed auxin signaling affects adventitious root outgrowth in Solanum
      dulcamara under complete submergence.
AB  - Flooding negatively affects the growth and even survival of most terrestrial
      plants. Upon flooding, the excess water quickly decreases the gas exchange
      between atmosphere and the submerged plant tissues, which leads to oxygen
      deficiency resulting in a plant cell energy crisis, and eventually plant death.
      Solanum dulcamara survives flooding by producing aerenchymatous adventitious
      roots (ARs) from pre-formed primordia on the stem, which replace the original
      flood-sensitive root system. However, we found that under complete submergence,
      AR outgrowth was impaired in S. dulcamara. In the present work, we tried to
      elucidate the mechanisms behind this phenomenon in particular the involvement of
      the phytohormones auxin, abscisic acid and jasmonic acid. Abscisic acid (ABA) is
      a negative regulator of AR outgrowth, but surprisingly the ABA content and
      signaling were decreased to a similar extent under both partial and complete
      submergence, suggesting that ABA might not be responsible for the difference in
      AR outgrowth. Auxin, which is necessary for AR outgrowth, was at similar
      concentrations in either partially or completely submerged primordia, but
      complete submergence resulted in a decrease of auxin signaling in the primordia.
      Application of 1-naphthaleneacetic acid (NAA) to completely submerged plants
      restored AR outgrowth, implying that auxin response in the rooting tissues of
      completely submerged plants was reduced. Furthermore, jasmonic acid (JA)
      concentrations did not differ between partial and complete submergence. To
      conclude, a disruption in the auxin signaling within S. dulcamara AR primordia
      may result in the abortion of AR outgrowth under complete submergence.

PMID- 29574326
TI  - Promoter analysis and functional implications of the selenium binding protein
      (SBP) gene family in Arabidopsis thaliana.
AB  - Selenium Betainding Protein (SBP, originally termed SBP56) was identified in
      mouse liver as a cytosolic protein that could bind radioactive selenium. SBPs are
      highly conserved proteins present in a wide array of species across all kingdoms
      and are likely to be involved in selenium metabolism. In Arabidopsis, the
      selenium binding protein (SBP) gene family comprises three genes (AtSBP1, AtSBP2
      and AtSBP3). AtSBP1 and AtSBP2 are clustered in a head-to-tail arrangement on
      chromosome IV, while AtSBP3 is located on chromosome III. In this work, we
      studied the promoter activity of the Arabidopsis SBP genes, determined their
      tissue specificity and showed that they are differentially regulated by sodium
      selenite and sodium selenate. All three SBP genes are upregulated in response to
      externally applied selenium compounds and the antioxidant NAC selectively
      downregulates SBP2. Although the effect on SBP2 levels was the most prominent, in
      all cases, the concurrent exposure of plants to selenite and the antioxidant
      supressed the expression of the SBP genes. We provide evidence that (at least)
      SBP1 expression is tightly linked to detoxification processes related to
      oxidative stress, since it is downregulated in the presence of NAC in selenium
      treated plants. Furthermore, our results suggest that SBP genes may participate
      in the mechanisms that sense redox imbalance.

PMID- 29574327
TI  - Clinical Significance of Peripheral Blood PCA3 Gene Expression in Early Diagnosis
      of Prostate Cancer.
AB  - Prostate cancer antigen 3 (PCA3) is one of the most promising genes currently
      investigated as a specific tumor biomarker for the diagnosis of prostate cancer.
      The purpose of this study was to investigate PCA3 gene expression in peripheral
      blood of prostate cancer (PCa) and benign prostate hyperplasia (BPH), and further
      to assess its clinical significance. We determined the copies of PCA3 mRNA in
      peripheral blood of PCa and BPH from 115 samples (PCa, n=78; BPH, n=37) using a
      quantitative reverse transcriptase-quantitative polymerase chain reaction (RT
      qPCR) with TaqMan assay. The sensitivity and specificity of PCA3 for the
      diagnosis of prostate cancer was compared with that of prostate-specific antigen
      (PSA) by receiver operating characteristic (ROC) curve analysis. To evaluate the
      association between PCA mRNA and disease progression, we analyzed PCA3 levels in
      connection with Gleason score and TNM stage of PCa. The clinical data revealed
      that expression of PCA3 gene was significantly higher in PCa than in BPH.
      Moreover, PCA3 mRNA was significantly higher in PCa patients with a Gleason score
      >=8 than in those with a Gleason score <=7 (P<.01). The results showed that the
      area under the curve (AUC) was 0.790, 0.606, and 0.620 for the copy number of
      PCA3, PSA level, and significantly free PSA (fPSA) level, respectively. Increased
      PCA3 in peripheral blood is correlated with PCa, and the detection of PCA3 may
      significantly reduce adverse screening outcomes. PCA3 gene expression in
      peripheral blood had a promising clinical application in the early diagnosis of
      PCa.

PMID- 29574328
TI  - The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1
      Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.
AB  - Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1
      pathway. A polymorphism in the 3' UTR of E2F1 gene may disrupt a binding site for
      miRNA and may affect its transcription level, thus modifying the susceptibility
      to radiotherapy and outcomes through this pathway. We evaluated the association
      of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with
      risk of recurrence of SCCOP in a cohort of 1008 patients. Log-rank test and
      univariate and multivariable Cox models were used to evaluate the associations.
      Compared with patients with E2F1-rs3213180 GG homozygous genotype, the patients
      with E2F1-rs3213180GC+CC variant genotypes had significantly better disease-free
      survival (log-rank P<.001) and decreased risk of SCCOP recurrence (HR, 0.4, 95%
      CI, 0.3-0.5) after multivariable adjustment. Furthermore, among patients with
      HPV16-positive tumors, the patients with E2F1-rs3213180 GC+CC variant genotypes
      had significantly better disease-free survival rates (log-rank P<.001) and lower
      recurrence risk than those with E2F1-rs3213180 GG homozygous genotype (HR, 0.2,
      95% CI, 0.1-0.4). Our findings suggest that E2F1-rs3213180 polymorphism may
      modulate the risk of recurrence in SCCOP patients, particularly for patients with
      HPV16-positive tumors of SCCOP. However, future larger population and functional
      studies are warranted to validate these results.

PMID- 29574329
TI  - In silico modelling of azole derivatives with tyrosinase inhibition ability:
      Application of the models for activity prediction of new compounds.
AB  - Tyrosinase is a metal containing multifunctional enzymes found in animals, fruits
      and vegetables and constitutes the primary cause for diseases resulting from
      overproduction of melanin as well as for browning of fruits. Inhibitors of the
      enzyme have thus gained increased importance in food and cosmetic industry. In
      the present work, a group of azole derivatives with tyrosinase inhibitory
      activity were explored to analyse the prime structural attributes of the potent
      inhibitors. In silico models have been developed in order to have a close insight
      regarding features of the molecular fragments that may affect the activity of the
      molecules conducively. The biological pharmacophore of the inhibitors that
      accounts for their interaction with the tyrosinase enzyme has been ascertained
      based on the development of a 3D pharmacophore model. The models thus developed
      were subsequently utilised for screening a set of compounds that were previously
      synthesised in-house and were reported to possess antioxidant activity. The final
      selection of active molecules in the screening process was done based on the
      docking interactions of the molecules with the tyrosinase enzyme and assessment
      of their degree of binding to the protein. Thus the developed models have been
      successfully utilised for identifying active compounds from a series of untested
      molecules.

PMID- 29574331
TI  - Butyrate from pectin fermentation inhibits intestinal cholesterol absorption and
      attenuates atherosclerosis in apolipoprotein E-deficient mice.
AB  - Short-chain fatty acids (SCFAs), the major products of dietary fiber fermentation
      by intestinal microflora, exert beneficial effects on pathogenesis of multiple
      metabolic diseases. The aim of this study was to determine whether SCFAs from
      fermentation of pectin (PE), a soluble dietary fiber, prevent the development of
      atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Male apoE-/- mice
      (8-week-old) were fed a high-fat, high-cholesterol diet (HCD; 21% wt/wt fat,
      0.15% wt/wt cholesterol) or HCD supplemented with 20% wt/wt PE (HCD+PE) alone or
      with antibiotics (HCD+PE + A) in drinking water for 12 weeks. Serum lipids and
      SCFAs concentrations, atherosclerotic lesion area, and intestinal morphology and
      function were measured. Caco-2 cells were treated with SCFAs to determine whether
      they affected the expression of genes involved in cholesterol absorption. HCD+PE
      treated mice exhibited decreased serum total and low-density lipoprotein
      cholesterol, and reduced atherosclerotic lesion area compared with HCD mice.
      These beneficial effects of PE were not observed in the HCD+PE+A group.
      Incubation of Caco-2 cells with butyrate, but not acetate and propionate, down
      regulated the expression of Niemann-Pick C1-Like 1 but up-regulated the ATP
      binding cassette transporters G5 and G8 (ABCG5 and G8) at the mRNA level.
      Butyrate treatment also increased transcriptional activity of liver X receptor in
      Caco-2 cells. Our data suggest that butyrate from PE intestinal fermentation
      protects mice from the progression of diet-induced atherosclerosis in apoE-/-
      mice. These findings suggest a novel mechanism by which dietary fiber may prevent
      the development of atherosclerosis.

PMID- 29574330
TI  - Rational engineering of synthetic microbial systems: from single cells to
      consortia.
AB  - One promise of synthetic biology is to provide solutions for biomedical and
      industrial problems by rational design of added functionality in living systems.
      Microbes are at the forefront of this biological engineering endeavor due to
      their general ease of handling and their relevance in many potential applications
      from fermentation to therapeutics. In recent years, the field has witnessed an
      explosion of novel regulatory tools, from synthetic orthogonal transcription
      factors to posttranslational mechanisms for increased control over the behavior
      of synthetic circuits. Tool development has been paralleled by the discovery of
      principles that enable increased modularity and the management of host-circuit
      interactions. Engineered cell-to-cell communication bridges the scales from
      intracellular to population-level coordination. These developments facilitate the
      translation of more than a decade of circuit design into applications.

PMID- 29574332
TI  - Fungal community, Fusarium head blight complex and secondary metabolites
      associated with malting barley grains harvested in Umbria, central Italy.
AB  - In recent years, due to the negative impact of toxigenic mycobiota and of the
      accumulation of their secondary metabolites in malting barley grains, monitoring
      the evolution of fungal communities in a certain cultivation area as well as
      detecting the different mycotoxins present in the raw material prior to malting
      and brewing processes have become increasingly important. In this study, a survey
      was carried out on malting barley samples collected after their harvest in the
      Umbria region (central Italy). Samples were analyzed to determine the composition
      of the fungal community, to identify the isolated Fusarium species, to quantify
      fungal secondary metabolites in the grains and to characterize the in vitro
      mycotoxigenic profile of a subset of the isolated Fusarium strains. The fungal
      community of barley grains was mainly composed of microorganisms belonging to the
      genus Alternaria (77%), followed by those belonging to the genus Fusarium (27%).
      The Fusarium head blight (FHB) complex was represented by nine species with the
      predominance of Fusarium poae (37%), followed by Fusarium avenaceum (23%),
      Fusarium graminearum (22%) and Fusarium tricinctum (7%). Secondary metabolites
      biosynthesized by Alternaria and Fusarium species were present in the analyzed
      grains. Among those biosynthesized by Fusarium species, nivalenol and enniatins
      were the most prevalent ones. Type A trichothecenes (T-2 and HT-2 toxins) as well
      as beauvericin were also present with a high incidence. Conversely, the number of
      samples contaminated with deoxynivalenol was low. Conjugated forms, such as
      deoxynivalenol-3-glucoside and HT-2-glucoside, were detected for the first time
      in malting barley grains cultivated in the surveyed area. In addition, strains of
      F. avenaceum and F. tricinctum showed the ability to biosynthesize in vitro high
      concentrations of enniatins. The analysis of fungal secondary metabolites, both
      in the grains and in vitro, revealed also the presence of other compounds, for
      which further investigations will be required. The combination of microbiological
      analyses, of molecular biology assays and of multi-mycotoxin screening shed light
      on the complexity of the fungal community and its secondary metabolites released
      in malting barley.

PMID- 29574333
TI  - Isolation and characterization of microorganisms and volatiles associated with
      Moroccan saffron during different processing treatments.
AB  - Saffron may be spoiled by a variety of microorganisms during cultivation,
      harvesting, and post harvesting. As saffron can be dried and stored in different
      ways, this preliminary study explored the natural microbiota present in Moroccan
      saffron when subjected to different drying techniques. An analysis of the
      carotenoid-derived volatiles present in the saffron was also carried out. The
      culturable microbiota of the saffron samples dried using different methods,
      namely in the shade (also called natural), in the sun, or in the oven, were
      studied using classical and molecular approaches. The effect of the drying
      methods on head-space chemical volatiles was also determined. Eighty-two isolates
      grown in the different culture media were chosen from the colonies, and genotype
      analysis grouped the microorganisms into 58 clusters, revealing a wide diversity.
      Out of the 82 isolates, 75 belonged to the Bacillaceae family. The other isolates
      were distributed within the Dietziaceae, Paenibacillaceae and Carnobacteriaceae
      families. The dominant species was Bacillus simplex, which was detected in all
      samples, regardless of the drying method used. Lysinibacillus macroides was
      dominant in the sun-dried saffron. No pathogens were isolated, but an isolate
      belonging to Dietzia maris, a potential human pathogenic species, was detected.
      The biodiversity indexes were linked to the drying method and generally decreased
      as the intensity of the treatment increased. The results of this preliminary work
      show that the different drying methods strongly influenced the microbiota and
      affect the saffron volatile profile. Further analysis will be needed to determine
      possible effects of selected microbiota on saffron volatiles.

PMID- 29574334
TI  - Immuno-oncology in head and neck squamous cell cancers: News from clinical
      trials, emerging predictive factors and unmet needs.
AB  - According to the new determinants of cancer immunity, head and neck squamous cell
      cancer (HNSCC) has to be considered as an immunogenic tumor for the relatively
      high number of somatic mutations giving rise to neoantigens recognized by T cell.
      HNSCC develop at a significant rate despite the antitumoral immune response
      indicating the existence of effective escape mechanisms. The lack of antigen
      presentation or co-stimulatory molecules required and immunosuppressive phenomena
      established by the tumor or the host microenvironment impair immune-mediated
      recognition and cancer control. Echoing the success in melanoma and NSCLC,
      strategies aimed to reverse this process and enhance the antitumor immunity are
      rapidly developing in HNSCC, as monotherapies, multidrug immunotherapies or
      associations with well-recognized treatments, like radiation and systemic
      therapies. According to the first published data, immunotherapy has shown
      promising results in the management of recurrent and metastatic (r/m) HNSCC. Anti
      PD-1 blockers have been recently approved by US and EU regulatory agencies in
      this setting. The encouraging results in r/m HNSCC prompted the incorporation of
      this approach also in the treatment of locally advanced disease. However, the
      strategies for the rational and evidence-based combinations to maximize clinical
      benefit are only starting to emerge. In this view, knowing in depth the specific
      properties of HNSCC and the underlying immunological conditions of the bearing
      hosts is an essential step. The role of immune system in the development and the
      management of HNSCC, the main mechanisms of tumor escape and the most recent
      results from clinical trials will be discussed herein.

PMID- 29574335
TI  - Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and
      low pH.
AB  - The recent Zika virus (ZIKV) outbreak in Brazil has suggested associations of
      this virus infection with neurological disorders, including microcephaly in
      newborn infants and Guillian-Barre syndrome in adults. Previous reports have
      shown that AXL, a transmembrane receptor tyrosine kinase protein, is essential
      for ZIKV infection of mammalian cells, but this remains controversial. Here, we
      have assessed the involvement of AXL in the ability of ZIKV to infect mammalian
      cells, and also the requirement for endocytosis and acidic pH. We demonstrated
      that AXL is essential for ZIKV infection of human fibroblast cell line HT1080 as
      the targeted deletion of the gene for AXL in HT1080 cells made them no longer
      susceptible to ZIKV infection. Our results also showed that infection was
      prevented by lysosomotropic agents such as ammonium chloride, chloroquine and
      bafilomycin A1, which neutralize the normally acidic pH of endosomal
      compartments. Infection by ZIKV was also blocked by chlorpromazine, indicating a
      requirement for clathrin-mediated endocytosis. Taken together, our findings
      suggest that AXL most likely serves as an attachment factor for ZIKV on the cell
      surface, and that productive infection requires endocytosis and delivery of the
      virus to acidified intracellular compartments.

PMID- 29574336
TI  - Broadly protective anti-hemagglutinin stalk antibodies induced by live attenuated
      influenza vaccine expressing chimeric hemagglutinin.
AB  - The development of influenza vaccines that can provide broad protection against
      all drifted seasonal virus variants, zoonotic infections and emerging pandemic
      strains, has been a priority for two decades. Here we propose a strategy of
      inducing broadly-reactive anti-stalk antibody by sequential immunizations with
      live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These
      vaccines are designed to contain identical hemagglutinin stalk domains from H1N1
      virus but antigenically unrelated globular head domains from avian influenza
      virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross
      protection of cHA-containing LAIVs compared to the relevant vaccine viruses
      expressing natural HAs, and this enhanced protection was driven by stalk-HA
      reactive IgG antibodies. The establishment of fully functional cross-protective
      immunity after two doses of cHA LAIV vaccination in naive animals suggests that a
      similar effect might be expected after a single cHA LAIV dose in primed
      individuals, or after two to three doses in naive children.

PMID- 29574337
TI  - Socioeconomic and ethnic inequalities in exposure to air and noise pollution in
      London.
AB  - BACKGROUND: Transport-related air and noise pollution, exposures linked to
      adverse health outcomes, varies within cities potentially resulting in exposure
      inequalities. Relatively little is known regarding inequalities in personal
      exposure to air pollution or transport-related noise. OBJECTIVES: Our objectives
      were to quantify socioeconomic and ethnic inequalities in London in 1) air
      pollution exposure at residence compared to personal exposure; and 2) transport
      related noise at residence from different sources. METHODS: We used individual
      level data from the London Travel Demand Survey (n = 45,079) between 2006 and
      2010. We modeled residential (CMAQ-urban) and personal (London Hybrid Exposure
      Model) particulate matter <2.5 MUm and nitrogen dioxide (NO2), road-traffic noise
      at residence (TRANEX) and identified those within 50 dB noise contours of
      railways and Heathrow airport. We analyzed relationships between household
      income, area-level income deprivation and ethnicity with air and noise pollution
      using quantile and logistic regression. RESULTS: We observed inverse patterns in
      inequalities in air pollution when estimated at residence versus personal
      exposure with respect to household income (categorical, 8 groups). Compared to
      the lowest income group (<L10,000), the highest group (>L75,000) had lower
      residential NO2 (-1.3 (95% CI -2.1, -0.6) MUg/m3 in the 95th exposure quantile)
      but higher personal NO2 exposure (1.9 (95% CI 1.6, 2.3) MUg/m3 in the 95th
      quantile), which was driven largely by transport mode and duration. Inequalities
      in residential exposure to NO2 with respect to area-level deprivation were larger
      at lower exposure quantiles (e.g. estimate for NO2 5.1 (95% CI 4.6, 5.5) at
      quantile 0.15 versus 1.9 (95% CI 1.1, 2.6) at quantile 0.95), reflecting low
      deprivation, high residential NO2 areas in the city centre. Air pollution
      exposure at residence consistently overestimated personal exposure; this
      overestimation varied with age, household income, and area-level income
      deprivation. Inequalities in road traffic noise were generally small. In logistic
      regression models, the odds of living within a 50 dB contour of aircraft noise
      were highest in individuals with the highest household income, white ethnicity,
      and with the lowest area-level income deprivation. Odds of living within a 50 dB
      contour of rail noise were 19% (95% CI 3, 37) higher for black compared to white
      individuals. CONCLUSIONS: Socioeconomic inequalities in air pollution exposure
      were different for modeled residential versus personal exposure, which has
      important implications for environmental justice and confounding in epidemiology
      studies. Exposure misclassification was dependent on several factors related to
      health, a potential source of bias in epidemiological studies. Quantile
      regression revealed that socioeconomic and ethnic inequalities in air pollution
      are often not uniform across the exposure distribution.

PMID- 29574338
TI  - Physiologically based pharmacokinetic (PBPK) modeling of human lactational
      transfer of methylmercury in China.
AB  - Methylmercury can readily cross the human placental barrier and the blood-brain
      barrier and cause damage to the vulnerable developing brains of the fetus and
      infants. Most of the previous studies on the maternal transfer of methylmercury
      to the next generation have focused on the prenatal period. In this study, human
      physiologically based pharmacokinetic (PBPK) models of methylmercury were
      established for breastfeeding mothers and suckling infants based on the existing
      model prototypes of previous studies. Relevant parameters of the models were
      modified, and the validation was conducted based on measured data in North China.
      The models could effectively describe the human lactational transfer of
      methylmercury, including the time-dependent methylmercury levels in different
      tissues and organs of the breastfeeding mothers and suckling infants. The results
      indicated that 77.2% and 14.9% of methylmercury were excreted via hair and breast
      milk, respectively, from breastfeeding mothers during the first year after
      delivery. Meanwhile, 79.2% was excreted from the suckling infants during the
      first year after delivery via hair. Lactational transfer of methylmercury was
      considered an important pathway of methylmercury exposure for the breastfeeding
      infants, which accounted for approximately 80% of the accumulated adverse impacts
      at the early stages of human development.

PMID- 29574340
TI  - Assessing frailty in the intensive care unit: A reliability and validity study.
AB  - PURPOSE: To describe pre-ICU frailty in critically ill patients using the
      Clinical Frailty Scale (CFS). METHODS: We included patients >=18years admitted to
      2 ICUs in Hamilton, Canada. The ICU Research Coordinator (RC) generated 3 CFS
      scores using: 1) chart review, 2) family interview, 3) patient interview.
      Subsequently, an overall impression was captured in a final score. Mean
      differences were calculated to assess the RC intra-rater reliability and inter
      rater reliability of chart reviews by the RC, Occupational Therapist (OT), and
      Geriatrics Resident (GR). Scores were also compared between younger and older
      patients. We also analyzed the relationship between CFS scores and mortality.
      RESULTS: We prospectively enrolled 150 patients (mean age 63.8 [SD 15.3] years,
      APACHE II score 21 [SD 7.3]). CFS were similar between RC, OT, and GR chart
      reviews (p>0.05 for all comparisons). There was no difference between RC chart
      review and RC final score, or between RC patient interview and RC final score.
      Scores following the RC family interview and the RC final score were
      significantly different (-0.24, 95% CI -0.38, -0.09, p<0.01). Each 1-point
      increase in the final CFS scored by the RC was weakly associated with ICU
      mortality (odds ratio 1.18, 95% CI 0.84-1.66, p=0.33), and hospital mortality (OR
      1.19, 95% CI 0.89, -1.59, p=0.24). CONCLUSIONS: CFS scores can be generated using
      medical chart review and can be reliably completed by ICU clinicians and research
      staff.

PMID- 29574339
TI  - Indoor black carbon of outdoor origin and oxidative stress biomarkers in patients
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: We assessed relationships between indoor black carbon (BC) exposure
      and urinary oxidative stress biomarkers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and
      malondialdehyde (MDA), in participants with chronic obstructive pulmonary disease
      (COPD). METHODS: Eighty-two participants completed in-home air sampling for one
      week prior to providing urine samples up to four times in a year. Weekly indoor
      and daily outdoor concentrations were used to estimate indoor daily lags and
      moving averages. There were no reported in-home BC sources, thus indoor levels
      closely represented outdoor BC infiltration. Mixed effects regression models with
      a random intercept for each participant were used to assess relationships between
      indoor BC and 8-OHdG and MDA, adjusting for age, race, BMI, diabetes, heart
      disease, season, time of urine collection, urine creatinine, and outdoor humidity
      and temperature. RESULTS: There were positive effects of BC on 8-OHdG and MDA,
      with the greatest effect the day before urine collection (6.9% increase; 95% CI
      0.9-13.3%, per interquartile range: 0.22 MUg/m3) for 8-OHdG and 1 to 4 days
      before collection (8.3% increase; 95% CI 0.03-17.3% per IQR) for MDA. Results
      were similar in models adjusting for PM2.5 not associated with BC and NO2 (10.4%
      increase, 95% CI: 3.5-17.9 for 8-OHdG; 8.1% increase, 95% CI: -1.1-18.1 for MDA).
      Effects on 8-OHdG were greater in obese participants. CONCLUSIONS: We found
      positive associations between BC exposure and 8-OHdG and MDA, in which
      associations with 8-OHdG were stronger in obese participants. These results
      suggest that exposure to low levels of traffic-related pollution results in lipid
      peroxidation and oxidative DNA damage in individuals with COPD.

PMID- 29574341
TI  - Postural reconfiguration and cycle-to-cycle variability in patients with work
      related musculoskeletal disorders compared to healthy controls and in relation to
      pain emerging during a repetitive movement task.
AB  - BACKGROUND: Movement variability in sustained repetitive tasks is an important
      factor in the context of work-related musculoskeletal disorders. While a popular
      hypothesis suggests that movement variability can prevent overuse injuries, pain
      evolving during task execution may also cause variability. The aim of the current
      study was to investigate, first, differences in movement behavior between
      volunteers with and without work-related pain and, second, the influence of
      emerging pain on movement variability. METHODS: Upper-body 3D kinematics were
      collected as 22 subjects with musculoskeletal disorders and 19 healthy volunteers
      performed a bimanual repetitive tapping task with a self-chosen and a given
      rhythm. Three subgroups were formed within the patient group according to the
      level of pain the participants experienced during the task. Principal component
      analysis was applied to 30 joint angle coordinates to characterize in a combined
      analysis the movement variability associated with reconfigurations of the
      volunteers' postures and the cycle-to-cycle variability that occurred during the
      execution of the task. FINDINGS: Patients with no task-related pain showed lower
      cycle-to-cycle variability compared to healthy controls. Findings also indicated
      an increase in movement variability as pain emerged, manifesting both as frequent
      postural changes and large cycle-to-cycle variability. INTERPRETATION: The
      findings suggested a relationship between work-related musculoskeletal disorders
      and movement variability but further investigation is needed on this issue.
      Additionally, the findings provided clear evidence that pain increased motor
      variability. Postural reconfigurations and cycle-to-cycle variability should be
      considered jointly when investigating movement variability and musculoskeletal
      disorders.

PMID- 29574342
TI  - Three-dimensional kinematics of the cervical spine using an electromagnetic
      tracking device. Differences between healthy subjects and subjects with non
      specific neck pain and the effect of age.
AB  - BACKGROUND: A cross-sectional observational study of three-dimensional cervical
      kinematics in 35 non-specific neck pain patients and 100 asymptomatic controls.
      To compare qualitative and quantitative aspects of cervical kinematics between
      healthy subjects and subjects with non-specific neck pain and to determine the
      effect of age on cervical kinematics in healthy subjects. METHODS: Three
      dimensional kinematics of active lateral bending and flexion-extension of 35
      patients and 100 controls were registered by means of an electromagnetic tracking
      system. The means of several kinematic parameters were compared using t-tests. In
      addition, we assessed the age-dependency of the three-dimensional kinematic
      parameters by stratifying the 100 control subjects in 6 age categories. FINDINGS:
      Comparison of the patient group with the control group reveals no statistically
      significant differences in qualitative and quantitative parameters. Analysis of
      the effect of age showed that the range of motion decreases significantly (p <
      0.01) with increasing age. In lateral bending, the ratio between axial rotation
      and lateral bending increases significantly (p < 0.01) among older subjects.
      Differences in acceleration, jerk and polynomial fit are seen between the age
      categories, but are not significant. INTERPRETATION: This study demonstrates no
      significant differences in kinematic parameters between healthy subjects and
      subjects with non-specific neck pain. Healthy subjects in higher age categories
      demonstrate higher ratios of coupled movements and lower ranges of motion. Future
      research should focus on classifying patients with non-specific neck pain in
      order to gain a better insight on possible subgroup specific differences in
      kinematics. More studies on this subject are warranted. LEVEL OF EVIDENCE: 4.

PMID- 29574344
TI  - Current and future modalities of dynamic control in metabolic engineering.
AB  - Metabolic engineering aims to maximize production of valuable compounds using
      cells as biological catalysts. When incorporating engineered pathways into host
      organisms, an inherent conflict is presented between maintenance of cellular
      health and generation of products. This challenge has been addressed through two
      main modalities of dynamic control: decoupling growth from production via two
      phase fermentations and autoregulation of pathways to optimize product formation.
      However, dynamic control can offer even greater potential for metabolic
      engineering through open-loop and closed-loop control modalities of the
      production phase. Here we review recent applications of dynamic control
      strategies in metabolic engineering. We then explore the potential of integrating
      biosensors and computer-assisted feedback control as a promising future modality
      of dynamic control.

PMID- 29574343
TI  - Enhanced colloidal stability and protein resistance of layered double hydroxide
      nanoparticles with phosphonic acid-terminated PEG coating for drug delivery.
AB  - Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to
      improve the colloidal and biological stability of nanoparticles. However, studies
      on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are
      very limited. The present work reported two functionalization approaches to
      synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid
      terminated PEG before and after LDH aging. The successful PEGylation was
      confirmed and suggested to be via electrostatic interaction and a ligand exchange
      process. Different functionalization approaches resulted in different binding
      types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity
      of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1.
      Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated
      LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar
      weight of PEG and anions intercalated in the LDHs. In a test to determine the
      extent of non-specific protein adsorption, the PEGylation was effective at
      resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with
      both functionalization methods investigated. Moreover, PEGylated LDH
      nanoparticles had no effect on cell viability up to 500 ug/mL, and demonstrated
      enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work
      indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is
      a promising strategy to improve the colloidal and biological stability of LDHs
      for biomedical applications.

PMID- 29574345
TI  - Range of therapeutic metformin concentrations in clinical blood samples and
      comparison to a forensic case with death due to lactic acidosis.
AB  - Due to a lack of reference values for blood concentration of metformin in the
      literature, the forensic evaluation of metformin findings in blood samples is
      difficult. Interpretations with regard to the assessment of blood concentrations
      as well as an estimation of the ingested metformin amounts are often vague.
      Furthermore, post mortem evaluation of death due to lactic acidosis because of
      metformin is difficult since renal performance or lactate concentrations can not
      always reliably be determined after death. To describe a concentration range in
      clinical samples after chronic use of metformin, metformin serum concentrations
      were determined in serum samples of 95 diabetic patients receiving daily doses of
      500mg-3000mg of metformin. The analyses of metformin was carried out using a
      validated high performance liquid chromatograph coupled to triple quadrupole mass
      spectrometry (LC-QQQ-MS). On average, metformin concentrations were 1846ng/mL
      (<LoQ-5560ng/mL) and independent of the prescribed daily dose. There was no
      correlation between plasma concentration and glomerular filtration rate except
      for the 1700mg daily dose collective (R2=0.707). Results of the herein presented
      study are useful for the interpretation of analytical metformin findings in
      forensic toxicology. The utility of the described concentration range is
      demonstrated by discussing a death case involving a fatal lactate acidosis after
      metformin intake and renal failure. Usefulness of the parameters metformin blood
      concentration, lactate concentration and glomerular filtration rate in post
      mortem cases of lactic acidosis due to metformin intoxication are discussed.

PMID- 29574346
TI  - Evaluation of three rapid oral fluid test devices on the screening of multiple
      drugs of abuse including ketamine.
AB  - Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their
      ability to detect common drugs of abuse; however, the performance of such devices
      on simultaneous screening for ketamine has been scarcely investigated. The
      present study evaluated three ROFT devices (DrugWipe(r) 6S, Ora-Check(r) and
      SalivaScreen(r)) on the detection of ketamine, opiates, methamphetamine,
      cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry
      (LCMS) assay was firstly established and validated for confirmation analysis of
      the six types of drugs and/or their metabolites. In the field test, the three
      ROFT devices were tested on subjects recruited from substance abuse
      clinics/rehabilitation centre. Oral fluid was also collected using Quantisal(r)
      for confirmation analysis. A total of 549 samples were collected in the study.
      LCMS analysis on 491 samples revealed the following drugs: codeine (55%),
      morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and
      cocaine (2%). No MDMA-positive cases were observed. Results showed that the
      overall specificity and accuracy were satisfactory and met the DRUID standard of
      >80% for all 3 devices. Ora-Check(r) had poor sensitivities (ketamine 36%,
      methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe(r) 6S showed
      good sensitivities in the methamphetamine (83%) and opiates (93%) tests but
      performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%).
      SalivaScreen(r) also demonstrated good sensitivities in the methamphetamine (83%)
      and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and
      cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The
      test completion rate (proportion of tests completed with quality control passed)
      were: 52% (Ora-Check(r)), 78% (SalivaScreen(r)) and 99% (DrugWipe(r) 6S).

PMID- 29574347
TI  - Authenticity assessment of banknotes using portable near infrared spectrometer
      and chemometrics.
AB  - Spectra recorded using a portable near infrared (NIR) spectrometer, Soft
      Independent Modeling of Class Analogy (SIMCA) and Linear Discriminant Analysis
      (LDA) associated to Successive Projections Algorithm (SPA) models were applied to
      identify counterfeit and authentic Brazilian Real (R$20, R$50 and R$100)
      banknotes, enabling a simple field analysis. NIR spectra (950-1650nm) were
      recorded from seven different areas of the banknotes (two with fluorescent ink,
      one over watermark, three with intaglio printing process and one over the serial
      numbers with typography printing). SIMCA and SPA-LDA models were built using 1st
      derivative preprocessed spectral data from one of the intaglio areas. For the
      SIMCA models, all authentic (300) banknotes were correctly classified and the
      counterfeits (227) were not classified. For the two classes SPA-LDA models
      (authentic and counterfeit currencies), all the test samples were correctly
      classified into their respective class. The number of selected variables by SPA
      varied from two to nineteen for R$20, R$50 and R$100 currencies. These results
      show that the use of the portable near-infrared with SIMCA or SPA-LDA models can
      be a completely effective, fast, and non-destructive way to identify authenticity
      of banknotes as well as permitting field analysis.

PMID- 29574348
TI  - Facial soft tissue thickness (FSTT) estimation models-And the strength of
      correlations between craniometric dimensions and FSTTs.
AB  - It has been speculated that craniometric dimensions can be used to improve
      estimations of facial soft tissue thickness (FSTT) in craniofacial
      identification. Subsequently, linear regression (LR) models have been published,
      but the practical utility of these models (lower errors than means) has never
      been tested/demonstrated. Using 71 living subjects measured by B-mode ultrasound,
      this study calculates and compares standard errors for previously published LR
      models and untrimmed FSTT means. Correlations between craniometric dimensions and
      FSTTs were calculated and regression model reproducibility examined by:
      generating new models using a 61 subject training set; and three-fold cross
      validation. Published regression models, applied to the above mentioned new
      individuals of this study, provided substantially worse estimates of ground truth
      FSTTs than untrimmed arithmetic means (mean Sest=4.0mm compared to 2.8mm, n=61
      71). Correlations between craniometrics and FSTTs were generally small (mean of
      absolute values=0.17, raw interval=-0.24 to 0.48) and only two of 15 previously
      published LR models were reproducible (mr-mr' and g-g')-i.e., contained the same
      independent variable with no more than one other different independent variable
      entering the model. Under three-fold cross-validation (training sets of 40-41
      individuals), no LR equation was reproduced across all three validation test
      runs. Basic craniometric dimensions do not appear to generally improve FSTT
      estimations and relationships between craniometric dimensions and FSTTs are much
      weaker and less reliable than previously thought. B-mode ultrasound data for
      adult Australians were pooled herein to provide larger sampled and updated FSTT
      statistics for this cohort (n=118-123).

PMID- 29574349
TI  - Fingermarks in blood: Mechanical models and the color of ridges.
AB  - This article treats fingermarks in blood on non-porous surfaces and addresses the
      question of "which came first": the fingermark or the blood. Three mechanical
      models were systematically examined: (1) A blood-contaminated finger pressed
      against a clean surface; (2) blood contaminates a latent print that had been
      placed on a clean surface; (3) A clean finger pressed against a blood
      contaminated surface. The questions of reliability and limits of all three models
      were discussed. The relevancy of the approach to "which came first", based solely
      on the color of ridges was questioned. The first mechanical model most simulated
      a real situation, when previously cleaned, a blood contaminated finger touched a
      clean Formica or glass surface with pressure of 100-500g. Concerning the second
      model, it was observed that in the case of a greasy latent print, placed on an
      inclined surface and contaminated with appropriate amount of blood, the color of
      ridges were normally darker than the color of its valleys. As for the third
      model, it was concluded that it works only in about 25% of cases. While
      investigating this model, two phenomena were observed: ridge color inversion and
      valley color inversion. In conclusion the color of ridges can not be the only and
      ultimate indicator to the question of "which came first", the fingermark or the
      blood stain.

PMID- 29574350
TI  - Pilot study of feature-based algorithm for breech face comparison.
AB  - A novel feature-based method, which is scale invariant feature transform (SIFT)
      and RANdom SAmple Consensus (RANSAC) integration algorithm, is introduced to
      promote the automated identification of the breech face impression, the most
      common mark left on the cartridge used for firearm evidence. SIFT algorithm is
      employed to extract the local extrema from examined impression as keypoints
      representing its invariant features, and to build the feature descriptor for each
      keypoint based on its local gradients in neighborhood. RANSAC is used to improve
      the matching performance among these keypoints and feature descriptors. With
      hypothesize-and-verify methods, RANSAC is able to construct the best model
      fitting initial matching pairs of keypoints and to guarantee the robust
      comparison result. Validation tests using 40 cartridge cases fired from pistols
      with 10 consecutively manufactured slides yielded a clear separation result,
      which strongly supports the effectiveness of the ensemble algorithm of SIFT and
      RANSAC. This application indicates the practical feasibility of feature-based
      algorithm and image processing technique in forensic science.

PMID- 29574351
TI  - Soil chemistry changes beneath decomposing cadavers over a one-year period.
AB  - Decomposing vertebrate cadavers release large, localized inputs of nutrients.
      These temporally limited resource patches affect nutrient cycling and soil
      organisms. The impact of decomposing cadavers on soil chemistry is relevant to
      soil biology, as a natural disturbance, and forensic science, to estimate the
      postmortem interval. However, cadaver impacts on soils are rarely studied, making
      it difficult to identify common patterns. We investigated the effects of
      decomposing pig cadavers (Sus scrofa domesticus) on soil chemistry (pH, ammonium,
      nitrate, nitrogen, phosphorous, potassium and carbon) over a one-year period in a
      spruce-dominant forest. Four treatments were applied, each with five replicates:
      two treatments including pig cadavers (placed on the ground and hung one metre
      above ground) and two controls (bare soil and bags filled with soil placed on the
      ground i.e. "fake pig" treatment). In the first two months (15-59 days after the
      start of the experiment), cadavers caused significant increases of ammonium,
      nitrogen, phosphorous and potassium (p<0.05) whereas nitrate significantly
      increased towards the end of the study (263-367 days; p<0.05). Soil pH increased
      significantly at first and then decreased significantly at the end of the
      experiment. After one year, some markers returned to basal levels (i.e. not
      significantly different from control plots), whereas others were still
      significantly different. Based on these response patterns and in comparison with
      previous studies, we define three categories of chemical markers that may have
      the potential to date the time since death: early peak markers (EPM), late peak
      markers (LPM) and late decrease markers (LDM). The marker categories will enhance
      our understanding of soil processes and can be highly useful when changes in soil
      chemistry are related to changes in the composition of soil organism communities.
      For actual casework further studies and more data are necessary to refine the
      marker categories along a more precise timeline and to develop a method that can
      be used in court.

PMID- 29574352
TI  - Visual characteristics for sequencing of overlapping bloodstain patterns.
AB  - The deposition sequence of overlapping bloodstain patterns can be valuable
      reconstructive information. A formal method for sequencing overlapping bloodstain
      patterns has yet to be published. We present a method for sequencing overlapping
      transfer and drip stains using visual characteristics. A survey was held amongst
      educated bloodstain pattern analysts to determine whether the newly acquired
      method will assist them in correctly sequencing these overlapping bloodstain
      patterns. Results showed a significant improvement of expert decisions: the
      percentage of overlapping stains correctly sequenced by participants increased
      from 57 to 79% using the visual characteristics defined in this study. These
      results suggest that a decision support system can be built, which helps
      investigators at the crime scene to sequence overlapping bloodstain patterns.

PMID- 29574353
TI  - Preliminary investigation of cognitive function in aged multiple sclerosis
      patients: Challenges in detecting comorbid Alzheimer's disease.
AB  - BACKGROUND: Cognitive impairment can be seen in patients of all ages with
      multiple sclerosis (MS). However, there is limited research on neurocognitive
      disorder in older adults with MS and how to detect Alzheimer's disease (AD) or
      its prodromal stage, amnestic mild cognitive impairment (aMCI). Thus, the MS
      clinician is challenged to discriminate between signs of MS-related cognitive
      decline versus a secondary neurodegenerative process. OBJECTIVE: Compare
      cognition in older MS patients to patients with AD and aMCI. METHODS: We
      evaluated cognitively impaired and unimpaired MS patients, AD patients, aMCI
      patients, and healthy controls (HCs), all elderly (n = 20 per group). AD and aMCI
      diagnoses were derived by consensus conference independent of the MS research
      project. Neuropsychological measures assessed domains commonly affected in AD,
      including verbal memory and expressive language. RESULTS: Cognitively impaired
      and unimpaired MS groups did not differ on any measures sensitive to AD.
      Unimpaired MS patients were comparable to HCs. Impaired MS patients showed
      decreased semantic fluency, similar to aMCI patients. Lastly, while both AD and
      aMCI groups had deficient memory retention, there was no evidence of a retention
      deficit in either MS group. CONCLUSION: Our findings suggest that the cognitive
      profiles of MS and AD are distinct. In contrast to AD, MS is not associated with
      impairment of memory consolidation. However, there may be overlap between
      cognitive deficits related to MS and aMCI. Thus, evidence of poor memory
      retention, in an older MS patient may merit comprehensive dementia evaluation.
      The study is preliminary and includes no AD biomarkers (e.g., amyloid imaging) to
      confirm or rule out AD pathology.

PMID- 29574354
TI  - Letter to the editor to the paper: "Acute and long-term effects of fingolimod on
      heart rhythm and heart rate variability in patients with multiple sclerosis".

PMID- 29574355
TI  - Early prediction of olanzapine-induced weight gain for schizophrenia patients.
AB  - The aim of this study was to determine whether weight changes at week 2 or other
      factors predicted weight gain at week 6 for schizophrenia patients receiving
      olanzapine. This study was the secondary analysis of a six-week trial for 94
      patients receiving olanzapine (5 mg/d) plus trifluoperazine (5 mg/d), or
      olanzapine (10 mg/d) alone. Patients were included in analysis only if they had
      completed the 6-week trial (per protocol analysis). Weight gain was defined as a
      7% or greater increase of the patient's baseline weight. The receiver operating
      characteristic curve was employed to determine the optimal cutoff points of
      statistically significant predictors. Eleven of the 67 patients completing the 6
      week trial were classified as weight gainers. Weight change at week 2 was the
      statistically significant predictor for ultimate weight gain at week 6. A weight
      change of 1.0 kg at week 2 appeared to be the optimal cutoff point, with a
      sensitivity of 0.92, a specificity of 0.75, and an AUC of 0.85. Using weight
      change at week 2 to predict weight gain at week 6 is favorable in terms of both
      specificity and sensitivity. Weight change of 1.0 kg or more at 2 weeks is a
      reliable predictor.

PMID- 29574356
TI  - Use of Ecological Momentary Assessment (EMA) in Non-Suicidal Self-Injury (NSSI):
      A systematic review.
AB  - Conceptualization and assessment of non-suicidal self-injury (NSSI) has evolved
      substantially in recent years. In both cross-sectional and longitudinal studies,
      NSSI and its related variables have traditionally been assessed retrospectively,
      leading to less precise studies of the mechanisms involved in the maintenance,
      cessation, or aggravation of this behavior. Ecological momentary assessment (EMA)
      enables real-time collection of patient states, which can be very useful in the
      study of the mechanisms implied in this behavior. This systematic review aims to
      elucidate the current status of EMA use in NSSI investigation. An exhaustive
      search in PubMed and PsycINFO was conducted up to September 2017. All papers
      included were focused on the study of NSSI using EMA. Studies with methodological
      diversity were included, which were afterwards organized according to main topic
      of studies. There were no ineligibility criteria based on age or diagnosis.
      Twenty-three papers were studied, the majority of which are short-term studies
      focused on the study of affect dynamics and the emotion-regulation function of
      NSSI. Implications of these results and recommendations for future research are
      discussed.

PMID- 29574358
TI  - Hormonal changes and folliculogenesis in female offspring of rats exposed to
      cadmium during gestation and lactation.
AB  - It has been suggested that the toxic effects of cadmium (Cd) may disrupt ovarian
      and uterine functions in adults. However, Cd exposure during gestation and
      lactation and its effects on the reproductive development in female offspring is
      still not clear, and the mechanisms underlying exposure toxicology remain mostly
      unexplored. To investigate how Cd exposure of female rats (F0) during gestation
      and lactation affects the reproductive development of their female offspring, we
      studied the steroidogenesis, folliculogenesis, puberty onset, and litter size of
      the first (F1) and second (F2) filial generations following F0 female rats which
      had been exposed to CdCl2. The mechanisms related to the early onset of puberty
      induced by such exposure in female offspring were explored. Maternal exposure to
      Cd dramatically increased the biosynthesis of steroid hormones in F1 female
      offspring by the activation of cAMP/PKA pathway and up-regulated expression of
      steroidogenesis related proteins such as StAR, CYP11A1, 3beta-HSD and CYP19A1.
      The high levels of steroid hormones contributed to an early puberty onset,
      promoted the differentiation and maturation of follicles, and led to the
      proliferation of endometrium that resulted in a uterus weight gain. The increased
      number of antral follicles eventually caused a big litter size. Despite of being
      free from additional Cd exposure, the levels of CYP11A1 and CYP19A1 in the
      ovaries of F2 female rats were also high, which resulted in a high concentration
      of serum progesterone. These results suggested that hormonal changes induced by
      exposure to Cd in utero might have a lasting effect beyond the first generation.
      These findings may help to better understand the origin of female sexual
      dysfunction in the developmental stages in general.

PMID- 29574357
TI  - Repression of adenosine triphosphate-binding cassette transporter ABCG2 by
      estrogen increases intracellular glutathione in brain endothelial cells following
      ischemic reperfusion injury.
AB  - The adenosine triphosphate-binding cassette efflux transporter ABCG2, which is
      located in the blood-brain barrier limits the entry of endogenous compounds and
      xenobiotics into the brain, and its expression and activity are regulated by
      estrogen. This study was aimed to define the role of ABCG2 in estrogen-mediated
      neuroprotection against ischemic injury. ABCG2 protein levels before and after
      ischemic stroke were increased in the brain of female mice by ovariectomy, which
      were reversed by estrogen replacement. In brain endothelial cell line bEnd.3,
      estrogen reduced the basal ABCG2 protein level and efflux activity and protected
      cells from ischemic injury without inducing ABCG2 expression. When bEnd.3 cells
      were transfected with ABCG2 small interfering RNA, ischemia-induced cell death
      was reduced, and the intracellular concentration of glutathione, an antioxidant
      that is transported by ABCG2, was increased. In addition, after ischemic stroke
      in ovariectomized mice, estrogen prevented the reduction of intracellular
      glutathione level in brain microvessels. These data suggested that the
      suppression of ABCG2 by estrogen is involved in neuroprotection against ischemic
      injury by increasing intracellular glutathione, and that the modulation of ABCG2
      activity offers a therapeutic target for brain diseases in estrogen-deficient
      aged women.

PMID- 29574359
TI  - Bioavailability and uptake of smelter emissions in freshwater zooplankton in
      northeastern Washington, USA lakes using Pb isotope analysis and trace metal
      concentrations.
AB  - The upper Columbia River and associated valley systems are highly contaminated
      with metal wastes from nearby smelting operations in Trail, British Columbia,
      Canada (Teck smelter), and to a lesser extent, Northport, Washington, USA (Le Roi
      smelter). Previous studies have investigated depositional patterns of airborne
      emissions from these smelters, and documented the Teck smelter as the primary
      metal contamination source. However, there is limited research directed at
      whether these contaminants are bioavailable to aquatic organisms. This study
      investigates whether smelter derived contaminants are bioavailable to freshwater
      zooplankton. Trace metal (Zn, Cd, As, Sb, Pb and Hg) concentrations and Pb
      isotope compositions of zooplankton and sediment were measured in lakes ranging
      from 17 to 144 km downwind of the Teck smelter. Pb isotopic compositions of
      historic ores used by both smelters are uniquely less radiogenic than local
      geologic formations, so when zooplankton assimilate substantial amounts of
      smelter derived metals their compositions deviate from local baseline
      compositions toward ore compositions. Sediment metal concentrations and Pb
      isotope compositions in sediment follow significant (p < 0.001) negative
      exponential and sigmoidal patterns, respectively, as distance from the Teck
      smelting operation increases. Zooplankton As, Cd, and Sb contents were related to
      distance from the Teck smelter (p < 0.05), and zooplankton Pb isotope
      compositions suggest As, Cd, Sb and Pb from historic and current smelter
      emissions are biologically available to zooplankton. Zooplankton from lakes
      within 86 km of the Teck facility display isotopic evidence that legacy ore
      pollution is biologically available for assimilation. However, without water
      column data our study is unable to determine if legacy contaminants are
      remobilized from lake sediments, or erosional pathways from the watershed.

PMID- 29574360
TI  - Acidic leaching of potentially toxic metals cadmium, cobalt, chromium, copper,
      nickel, lead, and zinc from two Zn smelting slag materials incubated in an acidic
      soil.
AB  - A column leaching study, coupled with acid deposition simulation, was conducted
      to investigate the leaching of potentially toxic metals (PTM) from zinc smelting
      slag materials (SSM) after being incubated in an acid Alfisol for 120 days at
      room temperature. Two SSMs (SSM-A: acidic, 10 yrs exposure with moderate high PTM
      concentrations versus SSM-B: alkaline, 2 yrs exposure with extremely high PTM
      concentrations), were used for the incubation at 0.5, 1, 2.5, 5 wt% amendment
      ratios in triplicate. Five leaching events were conducted at day 1, 3, 7, 14, and
      28, and the leaching of PTMs mainly occurred in the first three leaching events,
      with the highest PTM concentrations in leachate measured from 5 wt% SSM
      amendments. After leaching, 2.5, 12, 5.5, 14, 11, and 9 wt% of M3 extractable Pb,
      Zn, Cd, Co, Cr, and Ni could be released from 5 wt% SSM-A amended soils, being
      respectively 25, 12, 4, 2, 2, and 2 times more than those from 5 wt% SSM-B
      amended soils. In the leachates, the concentrations of PTMs were mostly affected
      by leachant pH and were closely correlated to the concentrations of Fe, Al, Ca,
      Mg and P with Cd, Pb, and Zn showing the most environmental concern. Visual
      MINTEQ 3.1 modeling suggested metallic ions and sulfate forms as the common
      chemical species of PTMs in the leachates; whereas, organic bound species showed
      importance for Cd, Pb, Cu, and Ni, and CdCl+ was observed for Cd. Aluminum
      hydroxy, phosphate, and sulfate minerals prevailed as the saturated minerals,
      followed by chloropyromorphite (Pb5(PO4)3Cl) and plumbogummite
      (PbAl3(PO4)2(OH)5.H2O) in the leachates. This study suggested that incubation of
      SSMs in acidic soil for a long term can enhance the release of PTMs as the forms
      of metallic ions and sulfate when subjected to acid deposition leaching.

PMID- 29574361
TI  - Diatom responses to sewage inputs and hydrological alteration in Mediterranean
      streams.
AB  - We analyzed the conjoint effects of sewage inputs and hydrological alteration on
      the occurrence of teratological forms and on the assemblage composition of stream
      benthic diatoms. The study was performed in 11 Mediterranean streams which
      received treated or untreated urban sewage (Impact sites, I), whose composition
      and morphological anomalies were compared to upstream unaffected (Control, C)
      sites. The impact sites had high concentrations of ammonium, phosphorus, and
      pharmaceutical compounds (antibiotics, analgesics, and anti-inflammatories),
      particularly in those receiving untreated sewage. Impact sites had a higher
      proportion of teratological forms as well as a prevalence of diatom taxa tolerant
      to pollution. The differences in the diatom assemblage composition between the
      paired C and I sites were the largest in the impacted sites that received
      untreated sewage inputs as well as in the systems with lower dilution capacity.
      In these sites, the diatom assemblage was composed by a few pollution-tolerant
      species. Mediterranean river systems facing hydrological stress are highly
      sensitive to chemical contamination, leading to the homogenization of their
      diatom assemblages.

PMID- 29574362
TI  - Effects of land use on the concentration and emission of nitrous oxide in
      nitrogen-enriched rivers.
AB  - Nitrous oxide (N2O) is a potent greenhouse gas that contributes to climate change
      and stratospheric ozone destruction. Nitrogen-enriched rivers are significant
      sources of atmospheric N2O. This study conducted a one-year field campaign in
      seven N-enriched rivers draining urban, rural, and agricultural land to determine
      the link between the production, concentrations, and emissions of N2O and land
      use. Estimated N2O fluxes varied between 1.30 and 1164.38 MUg N2O-N m-2 h-1 with
      a mean value of 154.90 MUg N2O-N m-2 h-1, indicating that rivers were the net
      sources of atmospheric N2O. Concentrations of N2O ranged between 0.23 and 29.21
      MUg N2O-N L-1 with an overall mean value of 3.81 MUg N2O-N L-1. Concentrations of
      ammonium and nitrate in urban and rural rivers were high in the cold season. The
      concentrations were also high in agricultural rivers in the wet season. N2O
      concentrations and emissions in rural and urban rivers followed a similar pattern
      to ammonium and a similar pattern to nitrate in agricultural rivers. A strong
      link between the concentrations and emissions of N2O and land use was observed.
      N2O concentrations in and emissions from the rivers draining the urban and rural
      areas were significantly higher than the rivers draining the agricultural areas
      (P < 0.01). Stepwise regression analysis indicated that dissolved N2O were
      primarily influenced by NH4+ in agricultural rivers and by NO3- in rural rivers;
      while dissolved N2O in urban rivers was primarily predicted by temperature and
      reflected the integrated impact of sewage input and river hydrology. Nitrate-N
      and NO3--O isotope data and linear regression of N2O and river water variables
      strongly indicated that dissolved N2O was mainly derived from nitrification in
      agricultural rivers and denitrification in rural and urban rivers.

PMID- 29574363
TI  - Effect of static foot posture on the dynamic stiffness of foot joints during
      walking.
AB  - BACKGROUND: The static foot posture has been related to the development of lower
      limb injuries. RESEARCH QUESTION: This study aimed to investigate the dynamic
      stiffness of foot joints during gait in the sagittal plane to understand the role
      of the static foot posture in the development of injuries. METHODS: Seventy
      healthy adult male subjects with different static postures, assessed by the Foot
      Posture Index (FPI) (30 normal, 20 highly pronated and 20 highly supinated), were
      recruited. Kinematic and kinetic data were recorded using an optical motion
      capture system and a pressure platform, and dynamic stiffness at the different
      stages of the stance was calculated from the slopes of the linear regression on
      the flexion moment-angle curves. The effect of foot type on dynamic stiffness and
      on ranges of motion and moments was analysed using ANOVAs and post-hoc tests, and
      linear correlation between dynamic stiffness and FPI was also tested. RESULTS:
      Highly pronated feet showed a significantly smaller range of motion at the ankle
      and metatarsophalangeal joints and also a larger range of moments at the
      metatarsophalangeal joint than highly supinated feet. Dynamic stiffness during
      propulsion was significantly greater at all foot joints for highly pronated feet,
      with positive significant correlations with the squared FPI. Highly supinated
      feet showed greater dynamic stiffness than normal feet, although to a lesser
      extent. Highly pronated feet during normal gait experienced the greatest decrease
      in the dorsiflexor moments during propulsion, normal feet being the most balanced
      regarding work generated and absorbed. SIGNIFICANCE: Extreme static foot postures
      show greater dynamic stiffness during propulsion and greater absorbed work, which
      increases the risk of developing injuries. The data presented may be used when
      designing orthotics or prostheses, and also when planning surgery that modifies
      joint stiffness.

PMID- 29574364
TI  - Prognostic relevance of distant metastases versus locally advanced disease in
      soft tissue sarcomas: An EORTC-STBSG database study.
AB  - INTRODUCTION: In patients with advanced soft tissue sarcoma (STS) treated with
      chemotherapy, WHO performance status, histologic subtype and histologic grade are
      known prognostic factors. Although the difference between the subgroups: locally
      advanced disease only, metastatic disease only and both local and metastatic
      disease is easily made, its prognostic relevance is thus far unknown. The aim of
      this EORTC database study was to study the difference in prognosis between these
      subgroups in patients receiving first-line chemotherapy for advanced STS.
      METHODS: A retrospective database analysis was performed on 2473 patients
      receiving first-line chemotherapy for advanced STS from 12 EORTC sarcoma trials
      to establish the difference in prognosis for the three subgroups. End-points were
      overall survival, progression-free survival and overall response rate. Factors
      studied were age, sex, histologic subtype, histologic grade, WHO performance
      status, treatment and time since initial diagnosis. RESULTS: Overall survival
      differed significantly between patients with locally advanced disease only, with
      metastatic disease only and with both locally advanced and metastatic disease
      with a median overall survival of 15.4, 12.9 and 10.6 months, respectively.
      Similar differences were seen for progression-free survival (5.8, 4.3 and 3.2
      months, respectively). CONCLUSION: This large retrospective database study shows
      that patients with advanced STSs treated with first-line chemotherapy with
      locally advanced disease, metastatic disease and both local and metastatic
      disease have different outcomes. This should be accounted for in future study
      design, interpretation and comparison of study results and daily practice.

PMID- 29574365
TI  - Health-related quality of life from the FALCON phase III randomised trial of
      fulvestrant 500 mg versus anastrozole for hormone receptor-positive advanced
      breast cancer.
AB  - BACKGROUND: The phase III randomised FALCON trial (NCT01602380) demonstrated
      improved progression-free survival with fulvestrant 500 mg versus anastrozole 1
      mg in endocrine therapy-naive postmenopausal women with hormone receptor-positive
      (HR+) locally advanced or metastatic breast cancer (LA/MBC). Furthermore, overall
      health-related quality of life (HRQoL) was maintained and comparable for
      fulvestrant and anastrozole. Here, we present additional analyses of patient
      reported HRQoL outcomes from FALCON. METHODS: Women with endocrine therapy-naive
      HR+ LA/MBC were randomised 1:1 to fulvestrant (days 0, 14, 28, then every 28 d)
      or anastrozole (daily) until disease progression or discontinuation. HRQoL was
      assessed by FACT-B questionnaire (TOI and FACT-B total score) at randomisation
      and every 12 weeks during treatment. HRQoL data post-treatment (with or without
      progression) were also collected. RESULTS: In total, 462 patients were randomised
      (fulvestrant, n = 230; anastrozole, n = 232). Compliance to FACT-B overall ranged
      from 60.0 to 97.4%. Mean change from baseline in TOI and FACT-B total score
      remained broadly stable (approximately +/- 3 points to week 132) and was similar
      between arms during treatment. HRQoL was also maintained in FACT-B subscales.
      Approximately one-third of patients had improved TOI (>=+6 points) and FACT-B
      (>=+8 points) total scores from baseline up to week 120 and 132, respectively, of
      treatment with fulvestrant (ranges 26.4-45.0% and 22.4-35.8%, respectively) and
      anastrozole (ranges 18.6-32.9%, and 22.7-37.9%, respectively). CONCLUSIONS: Mean
      change from baseline in TOI and FACT-B total score was maintained for fulvestrant
      and anastrozole; similar proportions of patients in both arms had improved TOI
      and FACT-B total scores. CLINICALTRIALS. GOV IDENTIFIER: NCT01602380.

PMID- 29574366
TI  - Long-term manure application increased greenhouse gas emissions but had no effect
      on ammonia volatilization in a Northern China upland field.
AB  - The impacts of manure application on soil ammonia (NH3) volatilization and
      greenhouse gas (GHG) emissions are of interest for both agronomic and
      environmental reasons. However, how the swine manure addition affects greenhouse
      gas and N emissions in North China Plain wheat fields is still unknown. A long
      term fertilization experiment was carried out on a maize-wheat rotation system in
      Northern China (Zea mays L-Triticum aestivum L.) from 1990 to 2017. The
      experiment included four treatments: (1) No fertilizer (CK), (2) single
      application of chemical fertilizers (NPK), (3) NPK plus 22.5t/ha swine manure
      (NPKM), (4) NPK plus 33.7t/ha swine manure (NPKM+). A short-term fertilization
      experiment was conducted from 2016 to 2017 using the same treatments in a field
      that had been abandoned for decades. The emissions of NH3 and GHGs were measured
      during the wheat season from 2016 to 2017. Results showed that after long-term
      fertilization the wheat yields for NPKM treatment were 7105kg/ha, which were
      higher than NPK (3880kg/ha) and NPKM+ treatments (5518kg/ha). The wheat yields
      were similar after short-term fertilization (6098-6887kg/ha). The NH3-N emission
      factors (EFamm) for NPKM and NPKM+ treatments (1.1 and 1.1-1.4%, respectively)
      were lower than NPK treatment (2.2%) in both the long and short-term
      fertilization treatments. In the long- and short-term experiments the nitrous
      oxide (N2O) emission factors (EFnit) for NPKM+ treatment were 4.2% and 3.7%,
      respectively, which were higher than for the NPK treatment (3.5% and 2.5%,
      respectively) and the NPKM treatment (3.6% and 2.2%, respectively). In addition,
      under long and short-term fertilization, the greenhouse gas intensities for the
      NPKM+ treatment were 33.7 and 27.0kg CO2-eq/kg yield, respectively, which were
      higher than for the NPKM treatment (22.8 and 21.1kg CO2-eq/kg yield,
      respectively). These results imply that excessive swine manure application does
      not increase yield but increases GHG emissions.

PMID- 29574367
TI  - Effects of topography and soil properties on soil selenium distribution and
      bioavailability (phosphate extraction): A case study in Yongjia County, China.
AB  - Selenium (Se) is an essential trace element for humans. In order to investigate
      how soil Se is influenced by topography and soil properties, we selected Yongjia
      County, an area with mountainous topography, as a study area. This study used
      cultivated soil data to comprehensively analyze the effects of topography and
      soil properties on Se mobility and bioavailability and to identify the key
      factors influencing Se distribution in the environment. Factors considered in
      this study were elevation, slope, topographic wetness index, the coefficient of
      weathering and eluviation, pH, organic matter, and Fe2O3. The concentration of
      total soil Se (0.382+/-0.123mgkg-1) was far higher than the background value of
      soil in China, and 98% of the soil samples were classified as having moderate Se
      levels (>0.175mgkg-1), indicating Yongjia County is a Se-rich region in China.
      Phosphate extracted Se accounted for an average of 9% of the total Se and was
      significantly associated with soil total Se, Fe2O3, pH, and the coefficient of
      weathering and eluviation. Fe2O3 primarily controlled Se adsorption, fixation,
      and availability in soil. Under the geo-environmental conditions in the study
      area, the total Se in the soil increased first and then decreased with increases
      in elevation, slope, and the topographic wetness index, and the phosphate
      extracted Se showed similar patterns except for the elevation. The findings
      showed that topographical attributes and soil physicochemical properties
      synthetically influenced the distribution and bioavailability of Se in soil.

PMID- 29574369
TI  - Seagrass Halophila stipulacea: Capacity of accumulation and biomonitoring of
      trace elements.
AB  - This study aimed to shed further light on the capacity of the seagrass Halophila
      stipulacea to accumulate and biomonitor the elements As, Cd, Cr, Cu, Hg, Mn, Ni,
      Pb, and Zn, present in water and sediments. Results showed that the organs of H.
      stipulacea accumulate different levels of trace elements, whose concentrations
      decrease mainly in the order of roots>rhizomes>leaves. The seagrass H. stipulacea
      showed levels of trace elements similar to those found in other Mediterranean
      seagrasses, e.g. Posidonia oceanica and Cymodocea nodosa. This study showed that
      H. stipulacea could act as a promising bioindicator of several elements, present
      in sediments, including As, Cd, Cu, Mn, Ni and Zn.

PMID- 29574368
TI  - Estimation of the consumption of illicit drugs during special events in two
      communities in Western Kentucky, USA using sewage epidemiology.
AB  - Sewage epidemiology is a cost-effective, comprehensive, and non-invasive
      technique capable of determining semi-real-time community usage of drugs
      utilizing the concentration of drug residues in wastewater, wastewater inflow,
      and the population size served by a wastewater treatment plant. In this study,
      semi-real-time consumption rates of ten illicit drugs were determined using
      sewage epidemiology during special events including Independence Day, the 2017
      solar eclipse, and the first week of an academic semester in the Midwestern
      United States. The average per-capita consumption rate of amphetamine,
      methamphetamine, cocaine, and THC were significantly different between two
      similar-sized communities during Independence Day observation week (p<0.046) and
      a typical week (p<0.001). Compared to a typical day, the consumption rate of
      amphetamine, methamphetamine, cocaine, morphine, and methadone was significantly
      higher on Independence Day (p<0.021) and during solar eclipse observation
      (p=0.020). The estimated percentage of the population that consumed cocaine in a
      community is similar to the conventionally estimated consumption of cocaine;
      however, the combined estimated population that consumed amphetamine and
      methamphetamine based on sewage epidemiology was ~2 to 4 fold higher than the
      conventional estimates. This study is the first to compare community use of drugs
      during special events in the USA using sewage epidemiology.

PMID- 29574370
TI  - Experimental study on the heat transfer characteristics of waste printed circuit
      boards pyrolysis.
AB  - In order to study the appropriate and advanced technology for recycling waste
      printed circuit boards (PCBs), a fixed bed pyrolysis device with stirring
      function has been designed and developed. The effect of rotating speed on the
      temperature distribution and mass change in the pyrolysis process of FR-4 PCB has
      been analyzed. The heat transfer and pyrolysis characteristics of different
      granular layers with and without stirring have been investigated. The results
      indicate that the stirring can change the main way of heat transfer from
      conduction to convection in the PCB layers. As the increase of rotating speed,
      the temperature rising rate of material at the bottom of the pyrolysis furnace
      gradually decreases, while the heating rate is increasing at the upper layer, and
      the temperature difference between the upper and bottom layers is gradually
      reduced. When the rotating speed varies from 0r/min to 18r/min, the weight loss
      of the material increases from 3.97% to 6.76%, and the overall pyrolysis degree
      is improved. During the pyrolysis process, the material layer can be divided into
      three zones along the vertical direction, namely complete pyrolysis zone, partial
      pyrolysis zone and non-pyrolysis zone. As the rotating speed is 0r/min, the
      thickness of each zones is 6cm, 6cm and 3cm, respectively. However, when the
      rotating speed is increased to 18r/min, the non-pyrolysis zone disappears, and
      the thickness of complete pyrolysis zone and partial pyrolysis zone increase to
      9cm and 6cm, respectively.

PMID- 29574371
TI  - Identifying efficient agricultural irrigation strategies in Crete.
AB  - Water scarcity and droughts are a major concern in most Mediterranean countries.
      Agriculture is a major user of water in the region and releases significant
      amounts of surface and ground waters, endangering the sustainable use of the
      available resources. Best Management Practices (BMPs) can mitigate the
      agriculture impacts on quantity of surface waters in agricultural catchments.
      However, identification of efficient BMPs strategies is a complex task, because
      BMPs costs and effectiveness can vary significantly within a basin. In this
      study, sustainable agricultural practices were studied based on optimal
      allocation of irrigation water use for dominant irrigated crops in the island of
      Crete, Greece. A decision support tool that integrates the Soil and Water
      Assessment Tool (SWAT) watershed model, an economic model, and multi-objective
      optimization routines, was used to identify and locate optimal irrigation
      strategies by considering crop water requirements, impact of irrigation changes
      on crop productivity, management strategies costs, and crop market prices. Three
      spatial scales (crop type, fields, and administrative regions) were considered to
      point out different approaches of efficient management. According to the
      analysis, depending on the spatial scale and complexity of spatial optimization,
      water irrigation volumes could be reduced by 32%-70% while preserving current
      agricultural benefit. Specific management strategies also looked at ways to
      relocate water between administrative regions (4 prefectures in the case of
      Crete) to optimize crop benefit while reducing global water use. It was estimated
      that an optimal reallocation of water could reduce irrigation water volumes by
      52% (148 Mm3/y) at the cost of a 7% (48 M?) loss of agricultural income, but
      maintaining the current agricultural benefit (626.9 M?). The study showed how the
      identification of optimal, cost-effective irrigation management strategies can
      potentially address the water scarcity issue that is becoming crucial for the
      viability of agriculture in the Mediterranean region.

PMID- 29574372
TI  - Post-wildfire management effects on short-term evolution of soil properties
      (Catalonia, Spain, SW-Europe).
AB  - Post-fire management practices after wildfires have an important impact on soil
      properties. Nevertheless, little research has been carried out. The aim of this
      study is to examine the impact of different post-wildfire forest management
      practices in a 10-month period immediately after a severe wildfire on soil
      properties. Two months after a wildfire, three experimental areas were designed,
      each one with different post-fire management: Cut and Remove (CR) where burned
      trunks were cut after fire and removed manually from the area; No Treatment (NT)
      where no intervention was carried out; and, Cut and Leave (CL) where burned
      trunks were cut and left randomly on topsoil. In each treatment, we collected
      nine samples (0-5cm deep). In total, we sampled 27 samples in each sampling date,
      two and ten months after the wildfire. The properties analyzed were aggregate
      stability (AS), total nitrogen (TN), soil organic matter (SOM), inorganic carbon
      (IC), C/N ratio, pH, electrical conductivity (EC), extractable calcium (Ca),
      magnesium (Mg), sodium (Na) and potassium (K). Soil C/N ratio was significantly
      higher in CR and CL treatments 10months after fire comparing to 2months after. On
      the other hand, pH, extractable Ca, Mg and K were significantly higher in all the
      treatments 2months after fire than 10months after. Aggregate stability, TN and
      SOM were significantly higher in CR comparing to CL, 10months after the fire. IC
      was significantly higher in CL than in NT treatment, also, 10months after the
      fire. Electrical conductivity was significantly higher in CR and CL treatments
      2months after fire comparing to 10months after. According to the results, CR and
      CL post-fire management did not differ importantly from the NT scenario, showing
      that manual wood management does not have detrimental impacts on soil properties
      compared to mechanical operations.

PMID- 29574373
TI  - Assessment of lead exposure among automobile technicians in Khyber Pakhtunkhwa,
      Pakistan.
AB  - Exposure to Pb among automobile technicians in selected towns of Khyber
      Pakhtunkhwa Province, Pakistan, was studied using a questionnaire, biological
      sampling (blood, hair, nails), and analysis of Pb biomonitoring data across
      various subgroups of occupation, age, and years of exposure. The study population
      included exposed automobile technicians (n=50) and a control group (n=50). The
      automobile technicians were further stratified into 4 groups: mechanics, auto
      body technicians, electricians, and painters. Mean Pb levels in biological
      samples of the automobile technicians were significantly higher than in the
      control group (P<0.01). The Pb concentrations (mean+/-standard deviation) in
      whole blood, hair, and nails of automobile technicians were 65.3+/-41.9MUgdL-1,
      23.6+/-11.2mgkg-1 and 29.7+/-14.5mgkg-1, respectively, whereas concentrations in
      the control group were 21.7+/-17.6MUgdL-1, 4.8+/-3.4mgkg-1 and 7.2+/-3.9mgkg-1.
      Fifty two percent of the automobile technicians had blood levels >50MUgdL-1, but
      only 14% of the control group exceeded this level. Considering that Pb blood
      levels of 50MUgdL-1 exceed maximum concentrations recommended by leading public
      health organizations, appropriate measures should be taken to protect the welfare
      of the exposed automobile technicians and their families.

PMID- 29574374
TI  - Changes in heavy metal bioavailability and speciation from a Pb-Zn mining soil
      amended with biochars from co-pyrolysis of rice straw and swine manure.
AB  - Biochar has been utilized as a good amendment to immobilize heavy metals in
      contaminated soils. However, the effectiveness of biochar in metal immobilization
      depends on biochar properties and metal species. In this study, the biochars
      produced from co-pyrolysis of rice straw with swine manure at 400 degrees C were
      investigated to evaluate their effects on bioavailability and chemical speciation
      of four heavy metals (Cd, Cu, Pb and Zn) in a Pb-Zn contaminated soil through
      incubation experiment. Results showed that co-pyrolysis process significantly
      change the yield, ash content, pH, and electrical conductivity (EC) of the
      blended biochars compared with the single straw/manure biochar. The addition of
      these biochars significantly increased the soil pH, EC, and dissolved organic
      carbon (DOC) concentrations. The addition of biochars at a rate of 3%
      significantly reduced the CaCl2-extractable metal concentrations in the order of
      Pb>Cu>Zn>Cd. The exchangeable heavy metals decreased in all the biochar-amended
      soils whereas the carbonate-bound metal speciation increased. The increase in
      soil pH and the decrease in the CaCl2 extractable metals indicated that these
      amendments can directly transform the highly availability metal speciation to the
      stable speciation in soils. In conclusion, biochar derived from co-pyrolysis of
      rice straw with swine manure at a mass ratio of 3:1 could most effectively
      immobilize the heavy metals in the soil.

PMID- 29574375
TI  - Characterization and health risk assessment of airborne pollutants in commercial
      restaurants in northwestern China: Under a low ventilation condition in
      wintertime.
AB  - Impacts on indoor air quality of dining areas from cooking activities were
      investigated in eight categories of commercial restaurants including Szechwan
      Hotpot, Hunan, Shaanxi Noodle, Chinese Barbecue, Chinese Vegetarian, Korean
      Barbecue, Italian, and Indian, in Northwestern China during December 2011 to
      January 2012. Chemical characterization and health risk assessment for airborne
      carbonyls, and particulate-bound polycyclic aromatic hydrocarbons (PAHs) and
      heavy metals were conducted under low ventilation conditions in wintertime. The
      highest total quantified carbonyls (Sigmacarbonyls) concentration of 313.6MUgm-3
      was found in the Chinese Barbecue, followed by the Szechwan Hotpot (222.6MUgm-3)
      and Indian (221.9MUgm-3) restaurants. However, the highest Sigmacarbonyls per
      capita was found at the Indian restaurant (4500MUgcapita-1), suggesting that
      cooking methods such as stir-fly and bake for spices ingredients released more
      carbonyls from thermal cooking processes. Formaldehyde, acetaldehyde, and acetone
      were the three most abundant species, totally accounting for >60% of mass
      concentrations of the Sigmacarbonyls. Phenanthrene, chrysene, and
      benzo[a]anthracene were the three most abundant PAHs. Low molecular weight
      fraction (SigmaPAHs<=178) had the highest contributions accounting for 40.6%
      65.7%, much greater than their heaver counterparts. Diagnostic PAHs ratios
      suggest that cooking fuel and environmental tobacco smoke (ETS) contribute to the
      indoor PAHs profiles. Lead was the most abundant heavy metal in all sampled
      restaurants. High quantity of nickel was also found in samples due to the
      emissions from stainless-steel made kitchen utensils and cookware and ETS. Cancer
      risk assessments on the toxic substances demonstrate that the working environment
      of dining areas were hazard to health. Formation of reactive organic species
      (ROS) from the cooking activities was evidenced by measurement of hydroxyl
      radical (OH) formed from simulating particulate matter (PM) react with surrogate
      lung fluid. The highest OH concentration of 294.4ngm-3 was detected in Chinese
      Barbecue. In addition, the elevation of the concentrations of PM and OH after non
      dining periods implies that the significance of formation of oxidizing-active
      species indoor at poor ventilation environments.

PMID- 29574376
TI  - April 2008 Saharan dust event: Its contribution to PM10 concentrations over the
      Anatolian Peninsula and relation with synoptic conditions.
AB  - An online-coupled regional Weather Research and Forecasting model with chemistry
      (WRF-Chem) is utilized incorporating 0.1 degrees *0.1 degrees  spatial resolution
      HTAP (Hemispheric Transport of Air Pollution) anthropogenic emissions to
      investigate the spatial and temporal distribution of a Saharan dust outbreak,
      which contributed to high levels (>50MUg/m3) of daily PM10 concentrations over
      Turkey in April 2008. Aerosol optical depth and cloud optical thickness
      retrievals from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor
      on board of Aqua satellite are used to better analyze the synoptic conditions
      that generated the dust outbreak in April 2008. A "Sharav" low pressure system,
      which transports the dust from Saharan source region over Turkey along the cold
      front, tends to move faster in WRF-Chem simulations than observed. This causes
      the predicted dust event to arrive earlier than observed leading to an
      overestimation of surface PM10 concentrations in WRF-Chem simulation at the
      beginning of the event.

PMID- 29574377
TI  - Atmospheric nitrate export in streams along a montane to urban gradient.
AB  - Nitrogen (N) emissions associated with urbanization exacerbate the atmospheric N
      influx to remote ecosystems - like mountains -, leading to well-documented
      detrimental effects on ecosystems (e.g., soil acidification, pollution of
      freshwaters). Here, the importance and fate of N deposition in a watershed was
      evaluated along a montane to urban gradient, using a multi-isotopic tracers
      approach (Delta17O, delta15N, delta18O of nitrate, delta2H and delta18O of
      water). In this setting, the montane streams had higher proportions of
      atmospheric nitrate compared to urban streams, and exported more atmospheric
      nitrate on a yearly basis (0.35 vs 0.10 kg-Nha-1yr-1). In urban areas, nitrate
      exports were driven by groundwater, whereas in the catchment head nitrate exports
      were dominated by surface runoff. The main sources of nitrate to the montane
      streams were microbial nitrification and atmospheric deposition, whereas
      microbial nitrification and sewage leakage contributed most to urban streams.
      Based on the measurement of delta15N and delta18O-NO3-, biological processes such
      as denitrification or N assimilation were not predominant in any streams in this
      study. The observed low delta15N and delta18O range of terrestrial nitrate (i.e.,
      nitrate not coming from atmospheric deposition) in surface water compared to
      literature suggests that atmospheric deposition may be underestimated as a direct
      source of N.

PMID- 29574378
TI  - Exploring synergistic benefits of Water-Food-Energy Nexus through multi-objective
      reservoir optimization schemes.
AB  - This study proposed a holistic three-fold scheme that synergistically optimizes
      the benefits of the Water-Food-Energy (WFE) Nexus by integrating the short/long
      term joint operation of a multi-objective reservoir with irrigation ponds in
      response to urbanization. The three-fold scheme was implemented step by step: (1)
      optimizing short-term (daily scale) reservoir operation for maximizing hydropower
      output and final reservoir storage during typhoon seasons; (2) simulating long
      term (ten-day scale) water shortage rates in consideration of the availability of
      irrigation ponds for both agricultural and public sectors during non-typhoon
      seasons; and (3) promoting the synergistic benefits of the WFE Nexus in a year
      round perspective by integrating the short-term optimization and long-term
      simulation of reservoir operations. The pivotal Shihmen Reservoir and 745
      irrigation ponds located in Taoyuan City of Taiwan together with the surrounding
      urban areas formed the study case. The results indicated that the optimal short
      term reservoir operation obtained from the non-dominated sorting genetic
      algorithm II (NSGA-II) could largely increase hydropower output but just slightly
      affected water supply. The simulation results of the reservoir coupled with
      irrigation ponds indicated that such joint operation could significantly reduce
      agricultural and public water shortage rates by 22.2% and 23.7% in average,
      respectively, as compared to those of reservoir operation excluding irrigation
      ponds. The results of year-round short/long-term joint operation showed that
      water shortage rates could be reduced by 10% at most, the food production rate
      could be increased by up to 47%, and the hydropower benefit could increase up to
      9.33 million USD per year, respectively, in a wet year. Consequently, the
      proposed methodology could be a viable approach to promoting the synergistic
      benefits of the WFE Nexus, and the results provided unique insights for
      stakeholders and policymakers to pursue sustainable urban development plans.

PMID- 29574379
TI  - Use of an improved high-throughput absolute abundance quantification method to
      characterize soil bacterial community and dynamics.
AB  - High-throughput sequencing has dramatically expanded our understanding of
      bacterial communities based on the information of the species types and their
      relative abundances. Recently, researchers have also become aware of a deficiency
      in not considering the absolute abundance in this technique. Combining two or
      more different methods has typically been used to achieve absolute quantification
      of microbial communities. However, making a combination of different methods not
      only is time-consuming but also involves potential uncertainty due to variations
      in the experimental conditions. To simplify the experimental procedure and
      improve the high-throughput absolute abundance quantification (HAAQ) of a soil
      bacterial community, we propose an HAAQ method that uses an internal standard
      strain (ISS) HAAQ-GFP to simultaneously obtain both the relative and absolute
      abundances in the soil bacterial community. The results showed that a soil
      bacterial community and its dynamics can be better characterized by the HAAQ
      method when the optimal concentrations of ISS HAAQ-GFP (105 to 107cellsg-1) were
      used, and a 16S rRNA gene copy number adjustment was applied. Based on the HAAQ
      method, we first found that soil bacterial absolute abundances at the genus level
      fitted well to the partial log-normal distribution function, and most genera
      concentrations were in the range of 103.5 to 106.5cellsg-1 in the test soils. Our
      case studies also indicated that more comprehensive descriptions of soil
      bacterial communities and their dynamics can be achieved by both the relative and
      absolute abundances than by the relative abundance alone. The improved HAAQ
      method can be potentially applied to other microbial ecological studies and to
      stimulating the development of quantitative bacterial ecology studies.

PMID- 29574380
TI  - Comparisons of the pharmacokinetic and tissue distribution profiles of
      withanolide B after intragastric administration of the effective part of Datura
      metel L. in normal and psoriasis guinea pigs.
AB  - A simple, highly sensitive ultra-performance liquid chromatography- electrospray
      ionization-mass spectrometry (LC-ESI-MS) method has been developed to quantify of
      withanolide B and obakunone (IS) in guinea pig plasma and tissues, and to compare
      the pharmacokinetics and tissue distribution of withanolide B in normal and
      psoriasis guinea pigs. After mixing with IS, plasma and tissues were pretreated
      by protein precipitation with methanol. Chromatographic separation was performed
      on a C18 column using aqueous (0.1% formic acid) and acetonitrile (0.1% formic
      acid) solutions at 0.4 mL/min as the mobile phase. The gradient program was
      selected (0-4.0 min, 2-98% B; 4.0-4.5 min, 98-2% B; and 4.5-5 min, 2% B).
      Detection was performed on a 4000 QTRAP UPLC-ESI-MS/MS system from AB Sciex in
      the multiple reaction monitoring (MRM) mode. Withanolide B and obakunone (IS)
      were monitored under positive ionization conditions. The optimized mass
      transition ion-pairs (m/z) for quantitation were 455.1/109.4 for withanolide B
      and 455.1/161.1 for obakunone.

PMID- 29574381
TI  - Tracheobronchial foreign body aspiration in laryngectomized patient with
      tracheoesophageal voice prosthesis.
AB  - A patient with a total laryngectomy and tracheoesophageal voice prosthesis
      presented with tracheobronchial aspiration of a Phillips-head screw that was
      swallowed inadvertently and aspirated around a loose-fitting prosthesis. A
      modified esophagram showed a screw in the right lung and free leakage of barium
      from the cervical esophagus around the prosthesis into the tracheobronchial tree.
      Chest radiographs and CT confirmed a screw in a right lower lobe bronchus with
      postobstructive pneumonia. When this complication occurs, it is important to
      extract the foreign body and, if necessary, to adjust or remove the prosthesis to
      prevent future aspiration pneumonias or foreign body aspiration.

PMID- 29574382
TI  - Design for an aberration corrected scanning electron microscope using miniature
      electron mirrors.
AB  - Resolution of scanning electron microscopes (SEMs) is determined by aberrations
      of the objective lens. It is well known that both spherical and chromatic
      aberrations can be compensated by placing a 90-degree bending magnet and an
      electron mirror in the beam path before the objective lens. Nevertheless, this
      approach has not led to wide use of these aberration correctors, partly because
      aberrations of the bending magnet can be a serious problem. A mirror corrector
      with two mirrors placed perpendicularly to the optic axis of an SEM and facing
      each other is proposed. As a result, only small-angle magnetic deflection is
      necessary to guide the electron beam around the top mirror to the bottom mirror
      and around the bottom mirror to the objective lens. The deflection angle, in the
      order of 50 mrad, is sufficiently small to avoid deflection aberrations. In
      addition, lateral dispersion at the sample plane can be avoided by making the
      deflection fields symmetric. Such a corrector system is only possible if the
      incoming beam can pass the top mirror at a distance in the order of millimeters,
      without being disturbed by the electric fields of electrodes of the mirror. It is
      proposed that condition can be satisfied with micro-scale electron optical
      elements fabricated by using MEMS technology. In the proposed corrector system,
      the micro-mirrors have to provide the exact negative spherical and chromatic
      aberrations for correcting the aberration of the objective lens. This exact
      tuning is accomplished by variable magnification between the micro-mirrors and
      the objective lens using an additional transfer lens. Extensive optical
      calculations are reported. Aberrations of the micro-mirrors were analyzed by
      numerical calculation. Dispersion and aberrations of the deflectors were
      calculated by using an analytical field model. Combination aberrations caused by
      the off-axis position of dispersive rays in the mirrors and objective lens were
      also analyzed. It is concluded that the proposed corrector system will be a
      promising candidate for simple and low-cost aberration correction in low-voltage
      SEMs.

PMID- 29574383
TI  - Interplay between COMT Val158Met, childhood adversities and sex in predicting
      panic pathology: Findings from a general population sample.
AB  - BACKGROUND: The single nucleotide polymorphism rs4680 of the catechol-O
      methyltransferase (COMT) gene has been implicated to be involved in the
      etiopathogenesis of panic. However, it remains unresolved whether rs4680 modifies
      the risk-association between early life stress and subsequent development of
      panic pathology. METHODS: The genotype of rs4680 was determined for n = 2242
      adults with European ancestry from the Study of Health in Pomerania (SHIP, a
      regional longitudinal cohort study from northeastern Germany). Lifetime fearful
      spells, panic attacks and panic disorder were assessed according to DSM-IV in
      2007-2010 (when participants were aged 29-89) using the Munich Composite
      International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were
      assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: Logistic
      regressions with interaction terms (adjusted for sex and age) revealed that
      rs4680 interacted with total childhood adversity, emotional abuse and physical
      abuse in predicting panic disorder: Respective childhood adversities predicted
      panic disorder in carriers of the Val/Met or Met/Met genotype, but not Val/Val
      genotype. Moreover, a 3-way interaction was found between rs4680, emotional abuse
      and sex in predicting panic attacks: Emotional abuse predicted panic attacks
      among male carriers of the Val/Val genotype and female carriers of the Val/Met or
      Met/Met genotype, but not among male carriers of the Val/Met or Met/Met genotype
      or female carriers of the Val/Val genotype. LIMITATIONS: Genotype data were
      derived by imputation. Childhood adversities and panic were assessed
      retrospectively. CONCLUSIONS: Especially (female) carriers of the Val/Met or
      Met/Met genotype of rs4680 might profit from targeted early interventions to
      prevent the onset of panic after childhood adversities.

PMID- 29574384
TI  - Combined effects of temperature and salinity on the demographic response of
      Proales similis (Beauchamp, 1907) and Brachionus plicatilis (Muller, 1786)
      (Rotifera) to mercury.
AB  - The demographic response of the brackish-water rotifers Proales similis and
      Brachionus plicatilis to mercury (0.5, 2, 8 and 32 MUg L-1 of HgCl2) at different
      salinity levels (10 and 200/00) and two temperature (25  degrees C and 32 
      degrees C) regimes were evaluated. Median lethal concentration (LC50) for P.
      similis and B. plicatilis was 10 and 16 MUg L-1, respectively, showing that
      Proales similis was more sensitive to mercury than B. plicatilis. The rate of
      population increase (r) for both species was greater at 100/00 salinity and 32 
      degrees C (ranged from 0.6 to 0.95 d-1). The r-value decreased as the
      concentration of mercury in the medium increased. Regardless of the temperature,
      at lower salinity and higher mercury concentration (32 MUg L-1), P. similis died
      within six days. The survivorship of P. similis and B. plicatilis was higher at
      25  degrees C than at 32  degrees C (ranged from 5 to 8 and 7-13 d,
      respectively). Fecundity was higher at 32  degrees C than at 25  degrees C for
      both rotifers species. There was a significant effect of the interaction among
      salinity, temperature, and mercury in both species on the reproductive variables
      such as net and gross reproductive rates, generation time and the rate of
      population increase. Considering the sensitivity of P. similis, we suggest that
      this species be included in the list of marine bioassay organisms.

PMID- 29574385
TI  - Effect of reducing agent on catalytic hydrodechlorination of aqueous-phase
      OCDD/F.
AB  - Removal/destruction of aqueous-phase octachlorodibenzo-p-dioxin (OCDD) and
      octachlorodibenzofuran (OCDF) via hydrodechlorination process (HDC) is
      experimentally evaluated over palladium/activated carbon (Pd/AC) catalyst. Pd
      catalyst is mainly used as active component for effectiveness in removing dioxin
      from wastewater. Studies on the removal of PCDD/Fs accomplished with HDC reaction
      in aqueous phase are limited and the influencing factors have not been clarified.
      In this study, high-concentration OCDD/F are selected as targets, and the effects
      of solvent and operating temperature on dechlorination efficiency are
      investigated via experimental tests. The results indicate that the highest
      hydrodechlorination efficiency is achieved with isopropanol as solvent. The
      OCDD/F removal efficiency achieved with the solution of 80% isopropanol is higher
      than that of 50% isopropanol, whereas the destruction efficiency of OCDD/F
      reveals the opposite trend. Generally, the removal and destruction efficiencies
      of PCDFs are higher than those of PCDDs. In addition, the activation energies of
      OCDD and OCDF are calculated with the Arrhenius equation as 24.8 and 23.1 kJ/mol,
      respectively. Stability tests are conducted with three cycles. Overall, the
      results indicate that a high performance (>=99%) can be achieved by combining
      hydrodechlorination with Pd/AC at a temperature range of 303-353 K, demonstrating
      that Pd/AC has good potential for removing PCDD/Fs from wastewater.

PMID- 29574386
TI  - Gender differences in mercury-induced hepatotoxicity: Potential mechanisms.
AB  - The accumulation of mercury in the liver causes hepatotoxicity. The organic anion
      transporter 3 (Oat3) and the multidrug-resistance associated protein 2 (Mrp2) are
      involved in the hepatic excretion of toxins and drugs and in the hepatic handling
      of mercury. The aim of this work was to study if there are gender-related
      differences in mercuric chloride (HgCl2)-induced hepatotoxicity in rats. Total
      mercury levels and protein expressions of Oat3 and Mrp2 in liver samples were
      also assessed to clarify the mechanisms underlying mercury-induced liver damage
      in male and female rats. Control and HgCl2-treated male and female Wistar rats
      were used. Hepatotoxicity was evaluated by plasma activity of transaminases and
      alkaline phosphatase, as well as by histopathological analysis. Oat3 and Mrp2
      expression was assessed by immunoblotting. Female rats displayed a higher HgCl2
      induced hepatotoxicity than male rats as demonstrated by the higher alterations
      in the plasma markers of liver damage and in the histopathology. The sex-related
      differences observed in the hepatic damage can be explained by the higher
      accumulation of mercury in liver from female rats. In this connection, after
      mercury treatment the expression of Mrp2 decreased in both sexes and the
      expression of Oat3 decreased only in males. The decreased in Oat3 abundance in
      the hepatocytes membranes in mercury-treated males would limit the uptake of
      mercuric ions into the liver protecting them from mercury hepatotoxicity.

PMID- 29574387
TI  - Towards "Precision Mining" of wastewater: Selective recovery of Cu from acid mine
      drainage onto diatomite supported nanoscale zerovalent iron particles.
AB  - This paper introduces the concept of 'Precision Mining' of metals which can be
      defined as a process for the selective in situ uptake of a metal from a material
      or media, with subsequent retrieval and recovery of the target metal. In order to
      demonstrate this concept nanoscale zerovalent iron (nZVI) was loaded onto
      diatomaceous earth (DE) and tested for the selective uptake of Cu from acid mine
      drainage (AMD) and subsequent release. Batch experiments were conducted using the
      AMD and nZVI-DE at 4.0-16.0 g/L. Results demonstrate nZVI-DE as highly selective
      for Cu removal with >99% uptake recorded after 0.25 h when using nZVI-DE
      concentrations >=12.0 g/L, despite appreciable concentrations of numerous other
      metals in the AMD, namely: Co, Ni, Mn and Zn. Cu uptake was maintained in excess
      of 4 and 24 h when using nZVI-DE concentrations of 12.0 and 16.0 g/L
      respectively. Near-total Cu release from the nZVI-DE was then recorded and
      attributed to the depletion of the nZVI component and the subsequent Eh, DO and
      pH recovery. This novel Cu uptake and release mechanism, once appropriately
      engineered, holds great promise as a novel 'Precision Mining' process for the
      rapid and selective Cu recovery from acidic wastewater, process effluents and
      leach liquors.

PMID- 29574388
TI  - Formation of DBPs and halogen-specific TOX in the presence of iopamidol and
      chlorinated oxidants.
AB  - Iopamidol is a known direct precursor to iodinated and chlorinated DBP formation;
      however, the influence of iopamidol on both iodo/chloro-DBP formation has yet to
      be fully investigated. This study investigated the effect of iopamidol on the
      formation and speciation of halogen-specific total organic halogen (TOX), as well
      as iodo/chloro-DBPs, in the presence of 3 source waters (SWs) from Northeast Ohio
      and chlorinated oxidants. Chlorination and chloramination of SWs were carried out
      at pH 6.5-9.0 and, different iopamidol and dissolved organic carbon (DOC)
      concentrations. Total organic iodine (TOI) loss was approximately equal (22-35%)
      regardless of SW. Total organic chlorine (TOCl) increased in all SWs and was
      substantially higher in the higher SUVA254 SWs. Iopamidol was a direct precursor
      to chloroform (CHCl3), trichloroacetic acid (TCAA), and dichloroiodomethane
      (CHCl2I) formation. While CHCl3 and TCAA exhibited different formation trends
      with varying iopamidol concentrations, CHCl2I increased with increasing iopamidol
      and DOC concentrations. Low concentrations of iodo-acids were detected without
      discernible trends. Total trihalomethanes (THMs), total haloacetic acids (HAAs),
      TOCl, and unknown TOCl (UTOCl) were correlated with fluorescence regional volumes
      and SUVA254. The yields of all these species showed a strong positive correlation
      with fulvic, humic, and combined humic and fulvic regions, as well as SUVA254.
      Iopamidol was then compared to the 3 SWs with respect to DBP yield. Although the
      SUVA254 of iopamidol was relatively high, it did not produce high yields of THMs
      and HAAs compared to the 3 SWs. However, chlorination of iopamidol did result in
      high yields of TOCl and UTOCl.

PMID- 29574389
TI  - Investigation of mercury adsorption and cyclic mercury retention over MnOx/gamma
      Al2O3 sorbent.
AB  - In this study mercury sorbent based on manganese oxides impregnated gamma-alumina
      was synthesized. Mercury retention characteristics were investigated by mercury
      speciation and thermal desorption experiments. No gaseous mercuric oxide was
      observed in mercury speciation experiments with a mercury mass balance ratio of
      89.11%. Maximum mercury desorption peak at 480  degrees C indicated that mercury
      was adsorbed in the form of mercuric oxide. Three cycles of mercury retention
      were tested with different thermal treatment in-between to evaluate the cyclic
      performance. Changes in surface phase and manganese chemistry before and after
      thermal treatment were characterized by XRD and XPS. Deterioration in mercury
      retention capacity was observed after thermal desorption at 500  degrees C, which
      was interpreted with reduced initial adsorption rate calculated by Pseudo-second
      order kinetic model. XPS studies suggested that atomic ratios of Mn4+/(Mn4++Mn3+)
      decreased from 73.2% to 32.3% and 33.9% after thermal desorption in N2 and air,
      respectively. The reduction of MnO2 to Mn2O3 was irreversible thus the mercury
      retention capacity could not be restored by thermal desorption at high
      temperatures. Spent sorbents that were reactivated at 200  degrees C in air
      without thermal desorption at 500  degrees C possessed considerable cycling
      performance for mercury retention due to the preserved Mn4+.

PMID- 29574390
TI  - PAHs in Indian diet: Assessing the cancer risk.
AB  - Food products such as bread, biscuits, tea, coffee, oils, chocolates, grapes,
      pepper and fishes belonging to different categories represent a significant part
      of everyday diet in India and other countries having variable cooking techniques.
      In this study, we evaluated cancer risks of long term exposure to polycyclic
      aromatic hydrocarbons (PAHs) through consumption of these products for eight
      societal groups in India. Total concentrations of PAHs in these products from
      India ranged from 0.18 to 61967 MUg kg-1 and the cancer risk values for the eight
      sections of Indian population ranged between 7.63E-10 to 5.05E+00, indicating
      product specific distribution of risk from non-significant to significant levels.
      Cereals, vegetables and decoctions contributed majorly to cancer risk and the
      most susceptible group identified was children. The spread of risk estimates
      followed Burr and Exponential distributions. To the best of our knowledge, this
      is the first study to develop information on the health risk faced by Indian
      population through dietary PAHs.

PMID- 29574391
TI  - A novel evaluation of the effect of lanthanum exposure on plant populations.
AB  - : The accumulation of rare earth elements (REEs) in the environment has recently
      become a new environmental problem. There have been many studies about the
      effects of REEs on plant at the individual, organ, cellular and genetic levels.
      Plants exist in populations under natural conditions, but little is known about
      the effects of REEs on plant populations. In this study, the effects of lanthanum
      (III) [La(III)] on the root module growth of soybean (Glycine max L) populations
      at different densities were investigated by simulating La(III) pollution. Results
      showed that at La(III) concentrations of 0.40 and 1.20 mM, both the root module
      growth parameters and leaf photosynthesis parameters were decreased, with 1.20 mM
      of La(III) causing a more significant decrease. In addition, the above parameters
      in low-density soybean populations decreased more significantly than those in
      high-density soybean populations. The above results show that the inhibitory
      effects of 0.40 and 1.20 mM of La(III) on the growth of root modules are closely
      related to the inhibition of photosynthesis in soybean population. Moreover, the
      inhibitory effect of La(III) on the growth of root modules of soybean population
      is enhanced as the La(III) concentration increases, while is weakened as plant
      population density increases. This study would provide a reference for the
      further research on the ecotoxicology of REEs, and show a new perspective and
      basis for the objective assessment of the environmental risks of REEs. ONE
      SENTENCE SUMMARY: La(III) pollution affects the root module growth and
      photosynthesis in soybean populations, and the effects vary depending on soybean
      population densities.

PMID- 29574392
TI  - The influence of carbon-encapsulated iron nanoparticles on elastic modulus of
      living human mesenchymal stem cells examined by atomic force microscopy.
AB  - Nanomaterials and nanoparticles are regarded as promising candidates for various
      biomedical applications due to their unique physicochemical properties. In this
      study, three types of carbon-encapsulated iron nanoparticles (CEINs) were
      synthesized and their impact on cellular changes was investigated by atomic force
      microscopy (AFM). The AFM experiment was additionally compared with conventional
      methods, such as colorimetric assay and other microscopic techniques. A
      significant difference of reduced Young's modulus of the cells was revealed, even
      at low concentration of nanoparticles in the culture medium. The AFM measurement
      proved to be a useful tool not only for visualization, but also for
      identification of local cellular changes at the nanoscale after exposure to
      carbon-encapsulated iron nanoparticles.

PMID- 29574393
TI  - The performance of one-step nucleic acid amplification assay for intraoperative
      detection of sentinel lymph node macrometastasis in breast cancer: An updated
      meta-analysis.
AB  - BACKGROUND: One-step nucleic acid amplification (OSNA) assay is a molecular
      diagnostic method for intraoperative detection of lymph node metastasis by
      amplifying cytokeratin 19 mRNA. We aim to further evaluate the performance of
      OSNA assay for the intraoperative diagnosis of sentinel lymph node metastasis in
      breast cancer. METHODS: PubMed, Cochrane Library, Web of Science databases were
      searched to retrieve related literature published up until December 2017. This
      meta-analysis was performed using a random-effects model. Risks of bias and
      quality assessments of included studies were evaluated and subgroup analysis was
      performed. RESULTS: Nineteen studies were included in this meta-analysis. For
      overall metastasis, the pooled sensitivity, specificity and area under the
      summary receiver-operating characteristic curve (AUC) were 0.90, 0.96 and 0.98,
      respectively. For macrometastasis, the pooled sensitivity, specificity and AUC
      were 0.85, 0.98 and 0.94, respectively. CONCLUSION: OSNA assay is an accurate
      molecular diagnosis for intraoperative detection of sentinel lymph node
      macrometastasis in breast cancer.

PMID- 29574394
TI  - Online learning versus blended learning of clinical supervisee skills with pre
      registration nursing students: A randomised controlled trial.
AB  - BACKGROUND: The World Health Organisation amongst others recognises the need for
      the introduction of clinical supervision education in health professional
      education as a central strategy for improving patient safety and patient care.
      Online and blended learning methods are growing exponentially in use in higher
      education and the systematic evaluation of these methods will aid understanding
      of how best to teach clinical supervision. OBJECTIVE: The purpose of this study
      was to test whether undergraduate nursing students who received clinical
      supervisee skills training via a blended learning approach would score higher in
      terms of motivation and attitudes towards clinical supervision, knowledge of
      clinical supervision and satisfaction of learning method, when compared to those
      students who received an online only teaching approach. DESIGN: A post-test-only
      randomised controlled trial. METHODS: Participants were a total of 122 pre
      registration nurses enrolled at one United Kingdom university, randomly assigned
      to the online learning control group (n = 60) or the blended learning
      intervention group (n = 62). The blended learning intervention group participated
      in a face-to-face tutorial and the online clinical supervisee skills training
      app. The online learning control group participated in an online discussion forum
      and the same online clinical supervisee skills training app. The outcome measures
      were motivation and attitudes using the modified Manchester Clinical Supervision
      Scale, knowledge using a 10 point Multiple Choice Questionnaire and satisfaction
      using a university training evaluation tool. Statistical analysis was performed
      using independent t-tests to compare the differences between the means of the
      control group and the intervention group. Thematic analysis was used to analyse
      responses to open-ended questions. RESULTS: All three of our study hypotheses
      were confirmed. Participants who received clinical supervisee skills training via
      a blended learning approach scored higher in terms of motivation and attitudes -
      mean (m) = 85.5, standard deviation (sd) = 9.78, number of participants (n) = 62 
      compared to the online group (m = 79.5, sd = 9.69, n = 60) (p = .001). The
      blended learning group also scored higher in terms of knowledge (m = 4.2, sd =
      1.43, n = 56) compared to the online group (m = 3.51, sd = 1.51, n = 57) (p =
      .015); and in terms of satisfaction (m = 30.89, sd = 6.54, n = 57) compared to
      the online group (m = 26.49, sd = 6.93, n = 55) (p = .001). Qualitative data
      supported results. CONCLUSION: Blended learning provides added pedagogical value
      when compared to online learning in terms of teaching undergraduate nurses
      clinical supervision skills. The evidence is timely given worldwide calls for
      expanding clinical skills supervision in undergraduate health professional
      education to improve quality of care and patient safety.

PMID- 29574395
TI  - Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia
      risk.
AB  - Acute myeloid leukemia (AML) induction traditionally includes seven days of
      cytarabine and three days of an anthracycline (7 + 3). Because of evidence of
      increased efficacy of cladribine combined with this regimen, we conducted a
      retrospective analysis of 107 AML patients treated with idarubicin, cytarabine
      and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%,
      with overall response of 79%. One-year survival overall was 59%, with 47% (27/57)
      among patients >=60 years old and 72% (36/50) in those <60 (Relative Risk [RR]
      1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and
      Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age
      >=60 years compared to <60 years. One year survival was 100% among favorable NCCN
      risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p <
      0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk
      (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that
      associated with age >=60 years (HR 2.2). We conclude that IAC is an effective AML
      induction regimen, NCCN leukemia risk predicts survival better than age in our
      population, and high intensity regimens can be justified in selected older
      patients.

PMID- 29574396
TI  - Comparison of intensive, pediatric-inspired therapy with non-intensive therapy in
      older adults aged 55-65 years with Philadelphia chromosome-negative acute
      lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVE: The standardization of treatment of older adults with
      Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is
      challenging, especially in the age range of 55-65 years. This study aimed to
      compare intensive, pediatric-inspired therapy with non-intensive therapy in this
      population of patients. PATIENTS AND METHODS: The outcomes of 67 patients
      prospectively included in two consecutive pediatric-inspired intensive protocols
      (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those
      from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07).
      RESULTS: Baseline patient and ALL characteristics were similar in both groups,
      except for a younger median age in the intensive group (medians: 58 vs. 62
      years). Patients treated intensively had a higher complete remission rate (85%
      vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to
      52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of
      treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%])
      and superior event-free survival at 2 years (37% [95%CI, 25%-49%) vs. 21% [8%
      34%], p = 0.002). On multivariable analysis the type of protocol was the only
      variable with independent significance for event-free survival (HR [95% CI]: 2
      [1.3, 3], p = .002). CONCLUSIONS: Compared with less intensive chemotherapy,
      pediatric-inspired intensive chemotherapy significantly improves the outcome of
      older adults with Ph-negative ALL in the age range of 55-65 years.

PMID- 29574397
TI  - High frequency of dicentric chromosomes detected by multi-centromeric FISH in
      patients with acute myeloid leukemia and complex karyotype.
AB  - Dicentric chromosomes (DCs) are considered markers of cancer in various
      malignancies. However, they can be overlooked when conventional analysis or
      multicolor fluorescence in situ hybridization (mFISH) is used to detect complex
      karyotypes. We analyzed the karyotypes of 114 patients with acute myeloid
      leukemia (AML) and complex karyotypes and verified the presence of monosomies by
      FISH using multi-centromeric probes. Monosomy was detected in 63% of patients by
      G-banding/mFISH and confirmed in 55% of patients by centromeric FISH. FISH
      analysis indicated a high frequency of DCs that were previously considered
      monosomies. In some cases, it was apparent that the derivative monocentric
      chromosome was a primary DC. DCs were formed mostly by chromosomes 17 and 20. In
      conclusion, chromosome loss and unbalanced translocation suggest the presence of
      a hidden DC or its previous existence. DCs undergo several stabilizing changes
      and can induce other chromosomal aberrations and/or the formation of new DCs.
      This can result in the clonal evolution of abnormal cells, which is considered an
      independent prognostic marker of an unfavorable disease course and short
      survival.

PMID- 29574398
TI  - Heterogeneous Multifrequency Direct Inversion (HMDI) for magnetic resonance
      elastography with application to a clinical brain exam.
AB  - A new viscoelastic wave inversion method for MRE, called Heterogeneous
      Multifrequency Direct Inversion (HMDI), was developed which accommodates
      heterogeneous elasticity within a direct inversion (DI) by incorporating first
      order gradients and combining results from a narrow band of multiple frequencies.
      The method is compared with a Helmholtz-type DI, Multifrequency Dual Elasto-Visco
      inversion (MDEV), both on ground-truth Finite Element Method simulations at
      varied noise levels and a prospective in vivo brain cohort of 48 subjects ages 18
      65. In simulated data, MDEV recovered background material within 5% and HMDI
      within 1% of prescribed up to SNR of 20 dB. In vivo HMDI and MDEV were then
      combined with segmentation from SPM to create a fully automated "brain palpation"
      exam for both whole brain (WB), and brain white matter (WM), measuring two
      parameters, the complex modulus magnitude |G*| , which measures tissue
      "stiffness", and the slope of |G*| values across frequencies, a measure of
      viscous dispersion. |G*| values for MDEV and HMDI were comparable to the
      literature (for a 3-frequency set centered at 50 Hz, WB means were 2.17 and 2.15
      kPa respectively, and WM means were 2.47 and 2.49 kPa respectively). Both methods
      showed moderate correlation to age in both WB and WM, for both |G*| and |G*|
      slope, with Pearson's r >= 0.4 in the most sensitive frequency sets. In
      comparison to MDEV, HMDI showed better preservation of recovered target shapes,
      more noise-robustness, and stabler recovery values in regions with rapid property
      change, however summary statistics for both methods were quite similar. By
      eliminating homogeneity assumptions within a fast, fully automatic,
      regularization-free direct inversion, HMDI appears to be a worthwhile addition to
      the MRE image reconstruction repertoire. In addition to supporting the literature
      showing decrease in brain viscoelasticity with age, our work supports a wide
      range of inter-individual variation in brain MRE results.

PMID- 29574400
TI  - Ultrasound-guided lumbar multifidus block provides effective postoperative
      analgesia for lumbar spine surgery.

PMID- 29574399
TI  - Riemannian metric optimization on surfaces (RMOS) for intrinsic brain mapping in
      the Laplace-Beltrami embedding space.
AB  - Surface mapping methods play an important role in various brain imaging studies
      from tracking the maturation of adolescent brains to mapping gray matter atrophy
      patterns in Alzheimer's disease. Popular surface mapping approaches based on
      spherical registration, however, have inherent numerical limitations when severe
      metric distortions are present during the spherical parameterization step. In
      this paper, we propose a novel computational framework for intrinsic surface
      mapping in the Laplace-Beltrami (LB) embedding space based on Riemannian metric
      optimization on surfaces (RMOS). Given a diffeomorphism between two surfaces, an
      isometry can be defined using the pullback metric, which in turn results in
      identical LB embeddings from the two surfaces. The proposed RMOS approach builds
      upon this mathematical foundation and achieves general feature-driven surface
      mapping in the LB embedding space by iteratively optimizing the Riemannian metric
      defined on the edges of triangular meshes. At the core of our framework is an
      optimization engine that converts an energy function for surface mapping into a
      distance measure in the LB embedding space, which can be effectively optimized
      using gradients of the LB eigen-system with respect to the Riemannian metrics. In
      the experimental results, we compare the RMOS algorithm with spherical
      registration using large-scale brain imaging data, and show that RMOS achieves
      superior performance in the prediction of hippocampal subfields and cortical
      gyral labels, and the holistic mapping of striatal surfaces for the construction
      of a striatal connectivity atlas from substantia nigra.

PMID- 29574401
TI  - A case report of incidental ectopic pancreatic tissue during laparoscopic
      appendicectomy.
AB  - INTRODUCTION: Ectopic or heterotopic pancreas is a congenital disorder defined as
      abnormally located pancreatic tissue found outside the pancreatic frame. It is a
      rare entity that occasionally causes symptoms depending on its location.
      PRESENTATION OF CASE: We present the case of an incidental finding of proximal
      jejunal ectopic pancreas in a middle-aged woman presenting with appendicitis.
      DISCUSSION AND CONCLUSION: Although rare it is necessary to be aware that jejunal
      ectopic pancreas can lead to jejunojejunal intussusception. Although diagnostic
      tools are emerging, pre operative diagnosis is difficult and resection is the
      management of choice of the incidentally found lesion.

PMID- 29574402
TI  - Oxidative stress markers imbalance in late-life depression.
AB  - BACKGROUND: Oxidative stress has been implicated in the pathophysiology of mood
      disorders in young adults. However, there is few data to support its role in the
      elderly. The primary aim of this study was to evaluate whether subjects with late
      life depression (LLD) presented with changes in oxidative stress response in
      comparison with the non-depressed control group. We then explored how oxidative
      stress markers associated with specific features of LLD, in particular cognitive
      performance and age of onset of major depressive disorder in these individuals.
      METHODS: We included a convenience sample of 124 individuals, 77 with LLD and 47
      non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative
      stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil
      content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity,
      glutathione reductase (GR) activity, and glutathione S-transferase (GST)
      activity. RESULTS: We found that participants with LLD had significantly higher
      free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity
      (p = 0.006) compared to controls. Free 8-isoprostane levels were also
      significantly correlated with worse scores in the initiation/perseverance (r = 
      0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the
      total scores (r = -0.21, p = 0.04) on the DRS. CONCLUSIONS: Our study provides
      robust evidence of the imbalance between oxidative stress damage, in particular
      lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD,
      and cognitive impairment in this population. Interventions aiming to reduce
      oxidative stress damage can have a potential neuroprotective effect for LLD
      subjects.

PMID- 29574403
TI  - Response to: 'Artificial stone-associated silicosis in the UK' by Barber et al.

PMID- 29574404
TI  - Response to: 'Reanalysis of non-occupational exposure to asbestos and the risk of
      pleural mesothelioma' by Finkelstein.

PMID- 29574405
TI  - Meta-analyses in environmental and occupational health.
AB  - OBJECTIVES: Meta-analyses are considered generally as the highest level of
      evidence, but concerns have been voiced about their massive, low-quality
      production. This paper aimed to evaluate the landscape of meta-analyses in the
      field of occupational and environmental health and medicine. METHODS: Using
      relevant search terms, all meta-analyses were searched for, but those published
      in 2015 were assessed for their origin, whether they included randomised trials
      and individual-level data and whether they had authors from the industry or
      consultancy firms. RESULTS: PubMed searches (last update February 2017)
      identified 1251 eligible meta-analyses in this field. There was a rapid increase
      over time (n=16 published in 1995 vs n=163 published in 2015). Of the 163
      eligible meta-analyses published in 2015, 49 were from China, followed at a
      distance by the USA (n=19). Only 16 considered randomised (intervention) trials
      and 13 included individual-level data. Only 1 of the 150 meta-analyses had
      industry authors and none had consultancy firm authors. As an example of
      conflicting findings, 12 overlapping meta-analyses addressed mobile phones and
      brain cancer risk and they differed substantially in number of studies included,
      eligibility criteria and conclusions. CONCLUSIONS: There has been a major
      increase in the publication of meta-analyses in occupational and environmental
      health over time, with the majority of these studies focusing on observational
      data, while a commendable fraction used individual-level data. Authorship is
      still limited largely to academic and non-profit authors. With massive production
      of meta-analyses, redundancy needs to be anticipated and efforts should be made
      to safeguard quality and protect from bias.

PMID- 29574406
TI  - Free PDA Membership To Be Included with Amazon Prime?

PMID- 29574407
TI  - Assessing the ProMCol classifier as a prognostic marker for non-metastatic
      colorectal cancer within the Melbourne Collaborative Cohort Study.

PMID- 29574409
TI  - A cohort study reporting normal oximetry values in healthy infants under 4 months
      of age using Masimo technology.
AB  - OBJECTIVE: To determine sleeping saturation indices in healthy infants using a
      modern pulse oximeter with motion artefact extraction technology. DESIGN:
      Prospective cohort. SETTING: Home. SUBJECTS: Healthy term infants. INTERVENTION:
      Nocturnal pulse oximetry at home at 1 month of age (Recording 1) and repeated at
      age 3-4 months (Recording 2). Parents documented sleep times. Visi-Download
      software (Stowood Scientific) analysed data with artefact and wake periods
      removed. MAIN OUTCOME MEASURES: Saturations (SAT50), desaturation index >4% (DI4)
      and >3% (DI3) from baseline/hour, delta index 12 s (DI12s), minimum saturations
      (SATmin), percentage time with saturations below 90% and 92%. RESULTS: Forty-five
      babies were studied at 1 month and 38 babies at 3-4 months. Mean (CI) SAT50, DI4,
      DI3, DI12s and SATmin (CI) were 97.05 (96.59 to 97.52), 16.16 (13.72 to 18.59),
      25.41 (22.00 to 28.82), 0.96 (0.88 to 1.04) and 80.4% (78.8% to 82.0%) at 1
      month, respectively, and 97.65 (97.19 to 98.12), 8.12 (6.46 to 9.77), 13.92
      (11.38 to 16.47), 0.72 (0.65 to 0.78) and 84.7% (83.3% to 86.1%) at 3-4 months.
      Median (CI) percentage times with saturations below 90% and 92% were 0.39 (0.26
      to 0.55) and 0.82 (0.60 to 1.23), respectively, at 1 month and 0.11 (0.06 to
      0.20) and 0.25 (0.17 to 0.44) at 3-4 months. For paired samples (n=32) DI4
      (P=0.006), DI3 (P=0.03), DI12s (P=0.001), percentage time with saturations below
      90% (P=0.001) and 92% (P=0.000) all fell significantly and SATmin (P=0.004) rose
      between the two recordings. CONCLUSION: Desaturation indices are substantially
      higher in young infants than older children where a DI4 over 4 is considered
      abnormal. These decrease by 3-4 months of age but still remain elevated compared
      with older children.

PMID- 29574410
TI  - Genomics for paediatricians: promises and pitfalls.
AB  - In recent years, there have been significant advances in genetic technologies,
      evolving the field of genomics from genetics. This has huge diagnostic potential,
      as genomic testing increasingly becomes part of mainstream medicine. However,
      there are numerous potential pitfalls in the interpretation of genomic data. It
      is therefore essential that we educate clinicians more widely about the
      appropriate interpretation and utilisation of genomic testing.

PMID- 29574412
TI  - Atrial fibrillation is target organ damage caused by an impaired haemodynamic
      state.

PMID- 29574411
TI  - Dual antiplatelet therapy in the 'real world'.

PMID- 29574413
TI  - Outcomes in patients treated with ticagrelor versus clopidogrel after acute
      myocardial infarction stratified by renal function.
AB  - OBJECTIVES: We aimed to analyse outcomes of ticagrelor and clopidogrel stratified
      by estimated glomerular filtration rate (eGFR) in a large unselected cohort of
      patients with acute myocardial infarction (MI). METHODS: We used follow-up data
      in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish
      Web-System for Enhancement and Development of Evidence-Based Care in Heart
      Disease Evaluated According to Recommended Therapies registry. The association
      between ticagrelor versus clopidogrel and the primary composite outcome of death,
      MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis
      at 1 year, was studied using adjusted Cox proportional hazards models,
      stratifying after eGFR levels. RESULTS: In total, 45 206 patients with MI
      discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The
      unadjusted 1-year event rate for the composite endpoint of death, MI or stroke
      was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for
      clopidogrel treatment in patients with eGFR>60 (n=33 668), eGFR30-60 (n=9803) and
      eGFR<30 (n=1735), respectively. After adjustment, ticagrelor as compared with
      clopidogrel was associated with a lower 1-year risk of the composite outcome
      (eGFR>60: HR 0.87, 95% CI 0.76 to 99, eGFR30-60: 0.82 (0.70 to 0.97), eGFR<30:
      0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding
      (eGFR>60: HR 1.10, 95% CI 0.90 to 1.35, eGFR30-60: 1.13 (0.84 to 1.51), eGFR<30:
      1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata. CONCLUSIONS:
      Treatment with ticagrelor as compared with clopidogrel in patients with MI was
      associated with lower risk for the composite of death, MI or stroke and a higher
      bleeding risk across all strata of eGFR. Of caution, bleeding events were more
      abundant in patients with eGFR<30.

PMID- 29574414
TI  - Lack of standardisation of ANA and implications for drug development and
      precision medicine.

PMID- 29574415
TI  - Response to: 'A20 haploinsufficiency (HA20): clinical phenotypes and disease
      course of patients with a newly recognised NF-kB-mediated autoinflammatory
      disease' by Aeschlimann et al.

PMID- 29574408
TI  - European evidence-based guidelines on pancreatic cystic neoplasms.
AB  - Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN)
      are lacking. This guideline is a joint initiative of the European Study Group on
      Cystic Tumours of the Pancreas, United European Gastroenterology, European
      Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European
      Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It
      replaces the 2013 European consensus statement guidelines on PCN. European and
      non-European experts performed systematic reviews and used GRADE methodology to
      answer relevant clinical questions on nine topics (biomarkers, radiology,
      endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic
      neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and
      pathology). Recommendations include conservative management, relative and
      absolute indications for surgery. A conservative approach is recommended for
      asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative
      indications for surgery in IPMN include a main pancreatic duct (MPD) diameter
      between 5 and 9.9 mm or a cyst diameter >=40 mm. Absolute indications for surgery
      in IPMN, due to the high-risk of malignant transformation, include jaundice, an
      enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN
      is recommended in patients who are fit for surgery. The European evidence-based
      guidelines on PCN aim to improve the diagnosis and management of PCN.

PMID- 29574417
TI  - Pulmonary arteriovenous malformation presenting as spontaneous haemothorax on
      transthoracic ultrasound.

PMID- 29574418
TI  - Endobronchial coil penetration into the pleural space.

PMID- 29574416
TI  - Occupational exposures and 20-year incidence of COPD: the European Community
      Respiratory Health Survey.
AB  - BACKGROUND: Occupational exposures have been associated with an increased risk of
      COPD. However, few studies have related objectively assessed occupational
      exposures to prospectively assessed incidence of COPD, using postbronchodilator
      lung function tests. Our objective was to examine the effect of occupational
      exposures on COPD incidence in the European Community Respiratory Health Survey.
      METHODS: General population samples aged 20-44 were randomly selected in 1991
      1993 and followed up 20 years later (2010-2012). Spirometry was performed at
      baseline and at follow-up, with incident COPD defined using a lower limit of
      normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD
      and without current asthma at baseline were included. Coded job histories during
      follow-up were linked to a Job-Exposure Matrix, generating occupational exposure
      estimates to 12 categories of agents. Their association with COPD incidence was
      examined in log-binomial models fitted in a Bayesian framework. FINDINGS: 3343
      participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up
      (1.4 cases/1000 person-years). Participants exposed to biological dust had a
      higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6,
      95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0
      to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population
      attributable fraction for these exposures was 21.0%. INTERPRETATION: These
      results substantially strengthen the evidence base for occupational exposures as
      an important risk factor for COPD.

PMID- 29574419
TI  - Facilitation of IL-22 production from innate lymphoid cells by prostaglandin E2
      prevents experimental lung neutrophilic inflammation.
AB  - Acute lung injury is a neutrophil-dominant, life-threatening disease without
      effective therapies and better understanding of the pathophysiological mechanisms
      involved is an urgent need. Here we show that interleukin (IL)-22 is produced
      from innate lymphoid cells (ILC) and is responsible for suppression of
      experimental lung neutrophilic inflammation. Blocking prostaglandin E2 (PGE2)
      synthesis reduces lung ILCs and IL-22 production, resulting in exacerbation of
      lung neutrophilic inflammation. In contrast, activation of the PGE2 receptor EP4
      prevents acute lung inflammation. We thus demonstrate a mechanism for production
      of innate IL-22 in the lung during acute injury, highlighting potential
      therapeutic strategies for control of lung neutrophilic inflammation by targeting
      the PGE2/ILC/IL-22 axis.

PMID- 29574420
TI  - Fifteen-minute consultation: Developing an advance care plan in partnership with
      the child and family.
AB  - An advance care plan (ACP) is the record of a discussion between an individual
      (where possible), their professional care givers and those close to them about
      their future care. When performed well, the process provides all those involved
      with the opportunity to talk honestly about the future allowing children and
      their families to retain autonomy and to influence how they are looked after.
      While this may represent a difficult area of practice for healthcare
      professionals, both staff and families appear to benefit when the process is
      fully informed and the child and family are actively involved. This article is
      enriched by the insight of two bereaved parents, who have engaged actively with
      the process of advance care planning. As a multidisciplinary writing team, we aim
      to share our experiences, in the context of recent national guidance, on the use
      of ACPs.

PMID- 29574421
TI  - Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201
      consecutive patients in a real-world setting.
AB  - BACKGROUND: We studied patients treated with the EmboTrap revascularization
      device in a prospective registry which is core laboratory evaluated by physicians
      from external centers. The goal was to determine how the EmboTrap would perform
      under the everyday conditions of a high-volume stroke center. METHODS: We
      examined all patients with acute stroke treated with the Embotrap device from
      October 2013 to March 2017 in our center. Imaging parameters and times were
      adjudicated by core laboratory personnel blinded to clinical information,
      treating physician, and clinical outcomes. Clinical evaluation was performed by
      independent neurologists and entered in a national registry. Evaluated endpoints
      were: successful revascularization (modified Thrombolysis in Cerebral Infarction
      (mTICI) 2b-3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS)
      0-2). RESULTS: 201 consecutive patients with a median NIH Stroke Scale (NIHSS)
      score of 15 (range 2-30) were included. 170 patients (84.6%) achieved mTICI 2b-3
      reperfusion. The median number of attempts was 2 (range 1-10) with 52.8% of the
      population achieving good functional outcomes (mRS 0-2) at 3 months. On
      univariate analysis, good functional outcome was associated with the number of
      attempts, puncture-to-reperfusion time, anterior circulation occlusion, and NIHSS
      score. On multivariate analysis, pre-treatment NIHSS (OR 0.845 per point, 95% CI
      0.793 to 0.908, P<0.001) and puncture-to-reperfusion time (OR 0.9952 per min, 95%
      CI 0.9914 to 0.9975, P=0.023) were associated with good functional outcomes at 3
      months. CONCLUSION: The Embotrap device has a high rate of successful
      reperfusion. Our core laboratory-audited single-center experience suggests the
      technical feasibility and safety of the Embotrap for first-line use in a real
      world setting.

PMID- 29574423
TI  - Palliative stenting for oesophagogastric cancer: tumour and host factors and
      prognosis.
AB  - OBJECTIVES: Palliative self-expandable metallic stent (SEMS) insertion is common
      in patients not suitable for resection of oesophagogastric (OG) cancer. Factors
      which may determine survival, however, are not clear. The present study examined
      the relationship between tumour and host factors, including the systemic
      inflammatory response and survival of patients undergoing palliative SEMS
      insertion. METHODS: Patients with a diagnosis of OG cancer who were considered
      suitable for palliative SEMS only without systemic therapy were identified.
      Patient characteristics including Eastern Cooperative Oncology Group performance
      status, radiological stage and modified Glasgow Prognostic Score (mGPS: 0-C
      reactive protein (CRP) <=10 mg/L; 1-CRP >10 mg/L; 2-CRP >10 mg/L; albumin <35
      g/L) were recorded prospectively. The relationship between such characteristics
      and 3-month survival was examined. RESULTS: 203 patients were included in the
      final analysis. All patients died during follow-up, with median survival from
      diagnosis 75 days (IQR 47-157). 78% of patients were systemically inflamed (mGPS
      >1). On multivariate analysis, only poor performance status (HR 1.23, p=0.025),
      metastatic disease (HR 2.27, p<0.001) and mGPS (HR 1.25, p=0.021) were associated
      with shorter survival. The combination of performance status and mGPS stratified
      3-month survival of patients without metastatic disease from 88% to 20% (p<0.001)
      and patients with metastases from 43% to 6% (p=0.059). Similar results were
      observed when analysis was restricted to patients with oesophageal and junctional
      cancer (M0: 83%-20%, p=0.008; M1: 33%-8%, p=0.082). CONCLUSION: Performance
      status, metastatic disease and mGPS are independent predictors of survival in
      patients with OG cancer undergoing palliative SEMS insertion. These routinely
      available markers provide a rational system on which to base decisions regarding
      prognosis and treatment.

PMID- 29574422
TI  - Maternal variants in NLRP and other maternal effect proteins are associated with
      multilocus imprinting disturbance in offspring.
AB  - BACKGROUND: Genomic imprinting results from the resistance of germline epigenetic
      marks to reprogramming in the early embryo for a small number of mammalian genes.
      Genetic, epigenetic or environmental insults that prevent imprints from evading
      reprogramming may result in imprinting disorders, which impact growth,
      development, behaviour and metabolism. We aimed to identify genetic defects
      causing imprinting disorders by whole-exome sequencing in families with one or
      more members affected by multilocus imprinting disturbance. METHODS: Whole-exome
      sequencing was performed in 38 pedigrees where probands had multilocus imprinting
      disturbance, in five of whom maternal variants in NLRP5 have previously been
      found. RESULTS: We now report 15 further pedigrees in which offspring had
      disturbance of imprinting, while their mothers had rare, predicted-deleterious
      variants in maternal effect genes, including NLRP2, NLRP7 and PADI6. As well as
      clinical features of well-recognised imprinting disorders, some offspring had
      additional features including developmental delay, behavioural problems and
      discordant monozygotic twinning, while some mothers had reproductive problems
      including pregnancy loss. CONCLUSION: The identification of 20 putative maternal
      effect variants in 38 families affected by multilocus imprinting disorders adds
      to the evidence that maternal genetic factors affect oocyte fitness and thus
      offspring development. Testing for maternal-effect genetic variants should be
      considered in families affected by atypical imprinting disorders.

PMID- 29574424
TI  - Why we need more poetry in palliative care.
AB  - OBJECTIVES: Although many well-known poems consider illness, loss and
      bereavement, medicine tends to view poetry more as an extracurricular than as a
      mainstream pursuit. Within palliative care, however, there has been a long
      standing interest in how poetry may help patients and health professionals find
      meaning, solace and enjoyment. The objective of this paper is to identify the
      different ways in which poetry has been used in palliative care and reflect on
      their further potential for education, practice and research. METHODS: A
      narrative review approach was used, drawing on searches of the academic
      literature through Medline and on professional, policy and poetry websites to
      identify themes for using poetry in palliative care. RESULTS: I identified four
      themes for using poetry in palliative care. These concerned (1) leadership, (2)
      developing organisational culture, (3) the training of health professionals and
      (4) the support of people with serious illness or nearing the end of life. The
      academic literature was mostly made up of practitioner perspectives, case
      examples or conceptual pieces on poetry therapy. Patients' accounts were rare but
      suggested poetry can help some people express powerful thoughts and emotions,
      create something new and feel part of a community. CONCLUSION: Poetry is one way
      in which many people, including patients and palliative care professionals, may
      seek meaning from and make sense of serious illnesses and losses towards the end
      of life. It may have untapped potential for developing person-centred
      organisations, training health professionals, supporting patients and for
      promoting public engagement in palliative care.

PMID- 29574425
TI  - Blood transfusion practice in the UK and Ireland: a survey of palliative care
      physicians.
AB  - OBJECTIVES: Red cell (blood) transfusions are used in palliative care to manage
      patients with symptomatic anaemia or when patients have lost blood. We aimed to
      understand current blood transfusion practice among palliative medicine doctors
      and compare this with National Institute for Health and Care Excellence (NICE)
      guidance. NICE guidance advocates more restrictive transfusion practice but is
      based on clinical trials in non-palliative care contexts; the extent to which
      these findings should be applied to palliative care remains unclear. METHODS:
      Four clinical vignettes of common clinical palliative care scenarios were
      developed. Members of the Association for Palliative Medicine were invited to
      complete the survey. Results were compared with acceptable responses based on
      current NICE recommendations and analysed to determine the influence of
      respondents' gender, experience or work setting. RESULTS: 27% of 1070 members
      responded. Overall, ideal or acceptable responses were selected by less than half
      of doctors to all four vignettes. Doctors were more liberal in prescribing blood
      transfusions than NICE guidance would advocate. Senior doctors were less likely
      to choose an acceptable response than junior colleagues. CONCLUSION: Palliative
      care practice is varied and not consistent with a restrictive blood transfusion
      policy. More recently trained doctors follow less liberal practices than senior
      colleagues. More direct evidence of benefits and harms of blood transfusion is
      needed in palliative care to inform practice.

PMID- 29574426
TI  - Delayed neurological deficits after endovascular placement of a pipeline
      embolisation device: clinical manifestation and treatment.
AB  - Endovascular treatment has been the mainstay of therapy for repair of both
      ruptured and unruptured cerebral aneurysms. Flow diverter devices offer a new
      option for the treatment of complex aneurysms that were previously not amenable
      to coiling. Procedural adverse effects include intracranial haemorrhage and
      ischaemic stroke, which usually occur on the same day. Delayed complications are
      rare. We report a case of a patient who underwent placement of a pipeline
      embolisation device and developed delayed neurological deficits, which were
      thought to be an inflammatory reaction to the hydrophilic coating used in
      guidewires and microcatheters. Our patient was treated with a course of steroids,
      with improvement of her neurological deficits and resolution of MRI findings. As
      the use of flow diverter devices has increased, variable and delayed
      complications of such therapy are increasingly being reported in the literature.

PMID- 29574427
TI  - Septic presentation of a giant fibroepithelial polyp of the vulva.
AB  - Fibroepithelial stromal polyps are mesenchymal lesions occurring typically in
      reproductive age women with a predilection for the vulvo-vaginal region.
      Malignancy may mimic this polyp in morphology, rendering further investigations
      including detailed histopathology mandatory. Histologically its characteristic
      features are stellate and multinucleate stromal cells identified near the
      epithelial-stromal interface. This case report discusses incidental finding of
      largest fibroepithelial polyp presented in a 31-year-old nulliparous woman. She
      was initially admitted with sepsis and detailed physical examination revealed a
      right-sided infected pedunculated labial mass measuring 20*21 cm. After initial
      resuscitation for sepsis, she was further investigated for the mass.
      Transabdominal ultrasound was essentially normal apart from a small fibroid 3*2
      cm in the anterior wall of the uterus. The vulval mass was removed under local
      and regional anaesthesia and was confirmed to be a giant fibroepithelial stromal
      polyp on histopathology. The woman recovered well and was followed up until 1
      year.

PMID- 29574428
TI  - Thyrotoxic crisis as an acute clinical presentation in a child.
AB  - A previously well, 4-year-old girl presented with a 4-6 weeks' history of
      increased appetite, weight loss, tiredness, sleep difficulty, excessive sweating,
      swelling in the neck and new-onset 'prominent, protruding eyes.' Family history
      revealed paternal grandmother receiving treatment for hyperthyroidism. Clinical
      assessment demonstrated features of thyrotoxicosis (tachycardia, warm
      peripheries, small smooth goitre with no nodules, exophthalmos). TFT (Free T4=101
      pmol/L, thyroid-stimulating hormone <0.05 mIU/L) with raised thyroid peroxidase
      antibody levels (TPO=541 IU/mL) confirmed autoimmune hyperthyroidism. Observation
      on the ward showed features of thyrotoxic crisis with persistent severe
      tachycardia on ECG (sinus tachycardia with left ventricular hypertrophy (LVH))
      and hypertension. Ultrasound thyroid showed diffuse thyroiditis with no focal
      lesion. Echocardiogram confirmed the above findings. A diagnosis of Graves'
      disease with thyrotoxic crisis was made. Antithyroid treatment (carbimazole) and
      beta-blocker (propranolol) was commenced. Thyrotoxic crisis resolved over 2 weeks
      and the child has continued to respond to carbimazole treatment at 1-year follow
      up.

PMID- 29574429
TI  - Placenta accreta complicated with peripartum cardiomyopathy.
AB  - A 33-year-old G2P1 was referred to our hospital due to placenta accreta. During
      perioperative preparations, the patient was diagnosed with having a peripartum
      cardiomyopathy. The patient underwent caesarean hysterectomy at 36 weeks with an
      associated 2 L blood loss. Haemodynamic maintenance and stabilisation during the
      operation were challenging, with the combinations of fluid therapy, blood
      transfusions as well as vasoactive, antifibrinolytic and haemostatic drug.
      Postoperatively, the patient was managed in the intensive care unit and was
      subsequently transferred to intermediate care after less than 24 hours'
      observation. She was stable enough to be moved to the obstetrics ward the next
      day.

PMID- 29574430
TI  - Rapidly expanding venous intracerebral haemorrhage with spot sign.
AB  - A 79-year-old woman was brought to the hospital with an acute-onset left
      haemiparesis. On initial examination, she had a pure sensorimotor syndrome with
      left-sided weakness and sensory disturbance. Her mental status was normal. She
      had normal visual fields to confrontation and no neglect. Her initial CT and CT
      angiogram revealed cerebral venous thrombosis with associated haemorrhage. A
      'spot sign' was visible on CT angiogram. Immediately following the CT scan, the
      patient had a rapidly progressive decline in level of consciousness, requiring
      endotracheal intubation. A follow-up CT scan 70 min later showed the haemorrhage
      had expanded dramatically, with mass effect, midline shift and herniation. After
      a discussion with the family, the patient was extubated and died the following
      day. This is the first case of a cerebral venous thrombosis with associated spot
      sign-positive haemorrhage and published clinical details that the authors are
      aware of.

PMID- 29574431
TI  - Worm in anterior chamber of the eye.
AB  - We report a case of a 42-year-old female patient who presented to the
      ophthalmology outpatient department with painful red eye for 1 month. Slit-lamp
      microscopy showed a live worm in the anterior chamber of left eye. The worm was
      surgically removed under topical anaesthesia. It was sent to the microbiology
      department for further identification and was found to be adult female Loaloa.

PMID- 29574432
TI  - Primary male factor infertility due to asthenospermia in maturity-onset diabetes
      of the young type 5 (MODY 5): uncommon presentation of an uncommon disease.
AB  - Mutations in hepatocyte nuclear factor-1beta gene result in a multisystemic
      syndrome where a monogenic form of diabetes (maturity-onset diabetes of young
      type 5; MODY 5) and renal anomalies, usually bilateral multiple cysts are the
      most characteristic findings. Many of them have pancreatic structural
      abnormalities as well. A plethora of extrapancreatic manifestations like altered
      liver function tests, hypomagnesaemia, hyperuricaemia with/without gout and
      urogenital malformations, particularly in females are also components of the
      syndrome. Structural malformation of male urogenital tract is rare in MODY 5,
      even rarer is asthenospermia. We encountered a young non-obese individual having
      insulin-requiring diabetes following secondary oral agent failure with primary
      male factor infertility secondary to asthenospermia. A suggestive family history,
      lack of acanthosis, negative pancreatic autoimmunity, hypomagnesaemia, bilateral
      renal and epididymal cysts, and absence of body and tail of pancreas pointed
      towards underlying MODY 5.

PMID- 29574433
TI  - Concurrent Sweet's syndrome and myopericarditis following mesalamine therapy.
AB  - Mesalamine, or 5-aminosalicylic acid, is a frequently used medication for the
      treatment of inflammatory bowel disease (IBD). We report the case of a 40-year
      old woman recently diagnosed with IBD and started on mesalamine, who presented
      with new onset tender skin lesions 3 days following medication administration.
      One day following the onset of skin lesions, the patient developed acute chest
      pain, shortness of breath, ECG changes, troponemia, C-reactive protein elevation
      and pericardial enhancement on cardiac MRI consistent with myopericarditis.
      Subsequent skin biopsy confirmed the diagnosis of Sweet's syndrome. On cessation
      of the drug, both the skin lesions and the cardiac symptoms resolved in
      combination with anti-inflammatory therapy. While mesalamine has been previously
      associated with myocarditis and pericarditis, to our knowledge this is the first
      case of coexisting Sweet's syndrome with myopericarditis in the context of
      mesalamine therapy.

PMID- 29574434
TI  - Herpes zoster ophthalmicus evolving into headache characterised as hemicrania
      continua.
AB  - Postherpetic neuralgia (PHN) is the most common chronic complication of herpes
      zoster infection. However, a few patients may develop different types of pain
      after herpetic lesions. We are reporting two patients who developed postherpetic
      hemicrania continua (HC). Case 1: a 54-year-old woman had a 10-month history of
      continuous left-sided pain with superimposed exacerbations. The pain started with
      the onset of herpetic lesions in the ophthalmic division. The lesions subsided in
      a few weeks. However, the pain persisted and it responded exclusively to
      indomethacin. Case 2: a 61-year-old woman developed clinical features pertinent
      to PHN. However, later on, the pattern and associated clinical features changed.
      The patient fulfilled the criteria of HC and showed a complete response to
      indomethacin. We suggest that every patient with PHN should be asked for cranial
      autonomic features and a trial of indomethacin should be given in refractory
      herpes zoster neuropathy.

PMID- 29574435
TI  - Autoimmune pancreatitis with concomitant autoimmune haemolytic anaemia.
AB  - Autoimmune pancreatitis (AIP) is an infrequent cause of acute pancreatitis, being
      more commonly associated with chronic pancreatitis. AIP can be associated with
      other autoimmune manifestations, including Sjogren's, inflammatory bowel disease,
      primary biliary cirrhosis, rheumatoid arthritis, hypothyroidism and sarcoidosis.
      Rarely, concurrent autoimmune haemolytic anaemia (AIHA) is observed, as seen in
      our case report of a 33-year-old postpartum woman.

PMID- 29574436
TI  - Superficial temporal artery pseudoaneurysm following facial trauma.
AB  - A 68-year-old man presented with rapid swelling of the right forehead 11 days
      after sustaining a laceration secondary to a fall. Presumed to be an abscess due
      to retained foreign body, needle aspiration was performed and arterial blood
      obtained. Doppler ultrasound revealed a 3 cm mixed echogenicity lesion with 'see
      sawing' internal Doppler flow arising from the superficial temporal artery (STA),
      in keeping with a pseudoaneurysm. Treatment options including interventional
      radiology and open surgery were considered. Open operative intervention with
      direct surgical ligation provided an excellent outcome. Delayed pseudoaneurysm of
      the STA is a rare complication of trauma but should be considered in the
      differential of a traumatic lateral forehead swelling to prevent complications
      and inappropriate investigations and management.

PMID- 29574437
TI  - Pneumatosis intestinalis in small bowel obstruction.

PMID- 29574438
TI  - A cluster randomised controlled trial to determine the effect of community
      mobilisation and advocacy on men's use of violence in periurban South Africa:
      study protocol.
AB  - OBJECTIVE: This paper describes the design and methods of a cluster randomised
      controlled trial (C-RCT) to determine the effectiveness of a community
      mobilisation intervention that is designed to reduce the perpetration of violence
      against women (VAW). METHODS AND ANALYSIS: A C-RCT of nine intervention and nine
      control clusters is being carried out in a periurban, semiformal settlement near
      Johannesburg, South Africa, between 2016 and 2018. A community mobilisation and
      advocacy intervention, called Sonke CHANGE is being implemented over 18 months.
      It comprises local advocacy and group activities to engage community members to
      challenge harmful gender norms and reduce VAW. The intervention is hypothesised
      to improve equitable masculinities, reduce alcohol use and ultimately, to reduce
      VAW. Intervention effectiveness will be determined through an audio computer
      assisted self-interview questionnaire with behavioural measures among 2600 men
      aged between 18 and 40 years at baseline, 12 months and 24 months. The primary
      trial outcome is men's use of physical and/or sexual VAW. Secondary outcomes
      include harmful alcohol use, gender attitudes, controlling behaviours,
      transactional sex and social cohesion. The main analysis will be intention-to
      treat based on the randomisation of clusters. A qualitative process evaluation is
      being conducted alongside the C-RCT. Implementers and men participating in the
      intervention will be interviewed longitudinally over the period of intervention
      implementation and observations of the workshops and other intervention
      activities are being carried out. ETHICS AND DISSEMINATION: Ethical approval was
      obtained from the University of the Witwatersrand Human Research Ethics Committee
      and procedures comply with ethical recommendations of the United Nations Multi
      Country Study on Men and Violence. Dissemination of research findings will take
      place with local stakeholders and through peer-reviewed publications, with data
      available on request or after 5 years of trial completion. TRIAL REGISTRATION
      NUMBER: NCT02823288; Pre-result.

PMID- 29574439
TI  - Randomised controlled trial of exercise to prevent shoulder problems in women
      undergoing breast cancer treatment: study protocol for the prevention of shoulder
      problems trial (UK PROSPER).
AB  - : Musculoskeletal shoulder problems are common after breast cancer treatment.
      Early postoperative exercises targeting the upper limb may improve shoulder
      function. This protocol describes a National Institute for Health Research-funded
      randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness
      of an early supervised structured exercise programme compared with usual care,
      for women at high risk of developing shoulder problems after breast cancer
      surgery. METHODS: This pragmatic two-armed, multicentre RCT is underway within
      secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to
      recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6
      and 12 months after randomisation. Recruitment processes and intervention
      development were optimised through qualitative research during a 6-month internal
      pilot phase. Participants are randomised to the PROSPER intervention or best
      practice usual care only. The PROSPER intervention is delivered by
      physiotherapists and incorporates three main components: shoulder-specific
      exercises targeting range of movement and strength; general physical activity and
      behavioural strategies to encourage adherence and support exercise behaviour. The
      primary outcome is upper arm function assessed using the Disabilities of the Arm,
      Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary
      outcomes include DASH subscales, acute and chronic pain, complications, health
      related quality of life and healthcare resource use. We will interview a
      subsample of 20 participants to explore their experiences of the trial
      interventions. DISCUSSION: The PROSPER study is the first multicentre UK clinical
      trial to investigate the clinical and cost-effectiveness of supported exercise in
      the prevention of shoulder problems in high-risk women undergoing breast cancer
      surgery. The findings will inform future clinical practice and provide valuable
      insight into the role of physiotherapy-supported exercise in breast cancer
      rehabilitation. PROTOCOL VERSION: Version 2.1; dated 11 January 2017 TRIAL
      REGISTRATION NUMBER: ISRCTN35358984; Pre-results.

PMID- 29574440
TI  - Projecting the effects of tobacco control policies in the USA through
      microsimulation: a study protocol.
AB  - INTRODUCTION: Smoking remains the leading cause of preventable death in the USA
      but can be reduced through policy interventions. Computational models of smoking
      can provide estimates of the projected impact of tobacco control policies and can
      be used to inform public health decision making. We outline a protocol for
      simulating the effects of tobacco policies on population health outcomes. METHODS
      AND ANALYSIS: We extend the Smoking History Generator (SHG), a microsimulation
      model based on data from the National Health Interview Surveys, to evaluate the
      effects of tobacco control policies on projections of smoking prevalence and
      mortality in the USA. The SHG simulates individual life trajectories including
      smoking initiation, cessation and mortality. We illustrate the application of the
      SHG policy module for four types of tobacco control policies at the national and
      state levels: smoke-free air laws, cigarette taxes, increasing tobacco control
      programme expenditures and raising the minimum age of legal access to tobacco.
      Smoking initiation and cessation rates are modified by age, birth cohort, gender
      and years since policy implementation. Initiation and cessation rate modifiers
      are adjusted for differences across age groups and the level of existing policy
      coverage. Smoking prevalence, the number of population deaths avoided, and life
      years gained are calculated for each policy scenario at the national and state
      levels. The model only considers direct individual benefits through reduced
      smoking and does not consider benefits through reduced exposure to secondhand
      smoke. ETHICS AND DISSEMINATION: A web-based interface is being developed to
      integrate the results of the simulations into a format that allows the user to
      explore the projected effects of tobacco control policies in the USA. Usability
      testing is being conducted in which experts provide feedback on the interface.
      Development of this tool is under way, and a publicly accessible website is
      available at http://www.tobaccopolicyeffects.org.

PMID- 29574441
TI  - Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's
      disease: a cross-sectional study of middle-aged adults from the broader New York
      City area.
AB  - OBJECTIVE: To investigate the effects of lifestyle and vascular-related risk
      factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in
      asymptomatic young to middle-aged adults. DESIGN: Cross-sectional, observational.
      SETTING: Broader New York City area. Two research centres affiliated with the
      Alzheimer's disease Core Center at New York University School of Medicine.
      PARTICIPANTS: We studied 116 cognitively normal healthy research participants
      aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI
      and had lifestyle (diet, physical activity and intellectual enrichment), vascular
      risk (overweight, hypertension, insulin resistance, elevated cholesterol and
      homocysteine) and cognition (memory, executive function, language) data.
      Estimates of cortical thickness for entorhinal (EC), posterior cingulate,
      orbitofrontal, inferior and middle temporal cortex were obtained by use of
      automated segmentation tools. We applied confirmatory factor analysis and
      structural equation modelling to evaluate the associations between lifestyle,
      vascular risk, brain and cognition. RESULTS: Adherence to a Mediterranean-style
      diet (MeDi) and insulin sensitivity were both positively associated with MRI
      based cortical thickness (diet: betas>=0.26, insulin sensitivity betas>=0.58,
      P<=0.008). After accounting for vascular risk, EC in turn explained variance in
      memory (P<=0.001). None of the other lifestyle and vascular risk variables were
      associated with brain thickness. In addition, the path associations between
      intellectual enrichment and better cognition were significant (betas>=0.25
      P<=0.001), as were those between overweight and lower cognition (betas>=-0.22,
      P<=0.01). CONCLUSIONS: In cognitively normal middle-aged adults, MeDi and insulin
      sensitivity explained cortical thickness in key brain regions for AD, and EC
      thickness predicted memory performance in turn. Intellectual activity and
      overweight were associated with cognitive performance through different pathways.
      Our findings support further investigation of lifestyle and vascular risk factor
      modification against brain ageing and AD. More studies with larger samples are
      needed to replicate these research findings in more diverse, community-based
      settings.

PMID- 29574442
TI  - Development of the Combined Assessment of Risk Encountered in Surgery (CARES)
      surgical risk calculator for prediction of postsurgical mortality and need for
      intensive care unit admission risk: a single-center retrospective study.
AB  - INTRODUCTION: Accurate surgical risk prediction is paramount in clinical shared
      decision making. Existing risk calculators have limited value in local practice
      due to lack of validation, complexities and inclusion of non-routine variables.
      OBJECTIVE: We aim to develop a simple, locally derived and validated surgical
      risk calculator predicting 30-day postsurgical mortality and need for intensive
      care unit (ICU) stay (>24 hours) based on routinely collected preoperative
      variables. We postulate that accuracy of a clinical history-based scoring tool
      could be improved by including readily available investigations, such as
      haemoglobin level and red cell distribution width. METHODOLOGY: Electronic
      medical records of 90 785 patients, who underwent non-cardiac and non-neuro
      surgery between 1 January 2012 and 31 October 2016 in Singapore General Hospital,
      were retrospectively analysed. Patient demographics, comorbidities, laboratory
      results, surgical priority and surgical risk were collected. Outcome measures
      were death within 30 days after surgery and ICU admission. After excluding
      patients with missing data, the final data set consisted of 79 914 cases, which
      was divided randomly into derivation (70%) and validation cohort (30%).
      Multivariable logistic regression analysis was used to construct a single model
      predicting both outcomes using Odds Ratio (OR) of the risk variables. The ORs
      were then assigned ranks, which were subsequently used to construct the
      calculator. RESULTS: Observed mortality was 0.6%. The Combined Assessment of Risk
      Encountered in Surgery (CARES) surgical risk calculator, consisting of nine
      variables, was constructed. The area under the receiver operating curve (AUROC)
      in the derivation and validation cohorts for mortality were 0.934 (0.917-0.950)
      and 0.934 (0.912-0.956), respectively, while the AUROC for ICU admission was
      0.863 (0.848-0.878) and 0.837 (0.808-0.868), respectively. CARES also performed
      better than the American Society of Anaesthesiologists-Physical Status
      classification in terms of AUROC comparison. CONCLUSION: The development of the
      CARES surgical risk calculator allows for a simplified yet accurate prediction of
      both postoperative mortality and need for ICU admission after surgery.

PMID- 29574443
TI  - Early initiation of post-sternotomy cardiac rehabilitation exercise training
      (SCAR): study protocol for a randomised controlled trial and economic evaluation.
AB  - INTRODUCTION: Current guidelines recommend abstinence from supervised cardiac
      rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice
      is not based on empirical evidence, thus imposing potentially unnecessary
      activity restrictions. Delayed participation in CR exercise training promotes
      muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited
      data suggest no detrimental effect of beginning CR exercise training as early as
      2 weeks post-surgery, but randomised controlled trials are yet to confirm this.
      The purpose of this trial is to compare CR exercise training commenced early (2
      weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to
      informing future CR guidelines for patients recovering from sternotomy. METHODS
      AND ANALYSIS: In this assessor-blind randomised controlled trial, 140 cardiac
      surgery patients, recovering from sternotomy, will be assigned to 8 weeks of
      twice-weekly supervised CR exercise training commencing at either 2 weeks (early
      CR) or 6 weeks (usual care CR) post-surgery. Usual care exercise training will
      adhere to current UK recommendations. Participants in the early CR group will
      undertake a highly individualised 2-3 week programme of functional mobility,
      strength and cardiovascular exercise before progressing to a usual care CR
      programme. Outcomes will be assessed at baseline (inpatient), pre-CR (2 or 6
      weeks post-surgery), post-CR (10 or 14 weeks post-surgery) and 12 months. The
      primary outcome will be change in 6 min walk distance. Secondary outcomes will
      include measures of functional fitness, quality of life and cost-effectiveness.
      ETHICS AND DISSEMINATION: Recruitment commenced on July 2017 and will complete by
      December 2019. Results will be disseminated via national governing bodies,
      scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER:
      NCT03223558; Pre-results.

PMID- 29574444
TI  - Opioid use and harms associated with a sustained-release tapentadol formulation:
      a postmarketing study protocol.
AB  - INTRODUCTION: It has been argued that tapentadol may pharmacologically have lower
      abuse potential than other pharmaceutical opioids currently available. However,
      there has been no comprehensive triangulation of data regarding use and harms
      associated with this formulation. A sustained-release formulation (SRF) of
      tapentadol (Palexia) was released in Australia in 2011 and listed for public
      subsidy in 2013. We summarise here the methods of a postmarketing study which
      will measure postintroduction: (1) population level availability, (2)
      extramedical use and diversion, (3) attractiveness for extramedical use and (4)
      associated harms, of tapentadol compared against other pharmaceutical opioids.
      METHODS AND ANALYSIS: We evaluated key sources on pharmaceutical use and harms in
      Australia. This review indicateddata from four sources that disaggregate
      pharmaceutical opioid formulations and capture tapentadol SRF could be
      triangulated. These data sources comprised: (1) national pharmaceutical opioid
      community sales data from 2011 to 2017, (2) national pharmaceutical opioid
      poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3)
      number of vendors on online marketplaces listing pharmaceutical opioids for sale
      and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms
      from interviews with people who regularly inject drugs in Australia. ETHICS AND
      DISSEMINATION: Ethics approval is not required for use of pharmaceutical sales
      data. Ethics approval has been obtained for use of national pharmaceutical opioid
      poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace
      data and interview data from people who inject drugs (HC12086). Key findings will
      be published mid-2018 in a peer-reviewed academic journal, and presented at
      various conferences and professional meetings.

PMID- 29574445
TI  - Health outcomes of patients with chronic disease managed with a healthcare kiosk
      in primary care: protocol for a pilot randomised controlled trial.
AB  - INTRODUCTION: The rising prevalence of chronic disease is leading to an increase
      in the demand for primary care services and a shortage of primary care physicians
      globally. Addressing these challenges calls for innovations in the healthcare
      delivery model with greater use of healthcare technology tools. We previously
      examined the feasibility of using an automated healthcare kiosk for the
      management of patients with stable chronic disease in the primary care setting.
      The aim of this follow-up study is to evaluate the health outcomes of patients
      with chronic disease who are on kiosk management compared with patients who are
      on routine management by nurse clinicians. METHODS AND ANALYSIS: The pilot study
      will be a two-armed randomised controlled trial of 120 patients with well
      controlled chronic disease on 4-monthly follow-up visits over a 12-month period.
      Patients with prior diagnoses of hypertension, hyperlipidaemia and/or diabetes
      will be included in the study and will be randomly assigned to intervention or
      control groups to receive kiosk or nurse management, respectively. The main
      primary outcome measure is the overall chronic disease control of the patients.
      Other primary outcome measures are the blood pressure and low-density lipoprotein
      cholesterol levels for patients without diabetes, and blood pressure, low-density
      lipoprotein cholesterol and haemoglobin A1c levels for patients with diabetes.
      Secondary outcome measures are visit duration, patient satisfaction with the
      management process, health-related quality of life and the occurrence of any
      adverse event. Data will be captured longitudinally at baseline, 4 months, 8
      months and 12 months, and will be analysed using multiple regression models.
      ETHICS AND DISSEMINATION: The study has been approved by the Singapore Health
      Services (SingHealth) Centralised Institutional Review Board (2017/2715).
      Findings of the study will be submitted for publication in peer-reviewed journals
      and presented at national and international conferences. TRIAL REGISTRATION
      NUMBER: NCT03274089; Pre-results.

PMID- 29574447
TI  - Correction: Evaluation of the district health management fellowship training
      programme: a case study in Iran.

PMID- 29574448
TI  - E-cigarette initiation and associated changes in smoking cessation and reduction:
      the Population Assessment of Tobacco and Health Study, 2013-2015.
AB  - BACKGROUND: The role of electronic cigarettes (e-cigarettes) in product
      transitions has been debated. METHODS: We used nationally representative data
      from the Population Assessment of Tobacco and Health Study waves 1 (2013-2014)
      and 2 (2014-2015) to investigate the associations between e-cigarette initiation
      and cigarette cessation/reduction in the USA. We limited the sample to current
      cigarette smokers aged 25+ years who were not current e-cigarette users at wave
      1. We modelled 30-day cigarette cessation and substantial reduction in cigarette
      consumption as a function of e-cigarette initiation between surveys using
      multivariable logistic regression. RESULTS: Between waves 1 and 2, 6.9% of
      cigarette smokers who were not current e-cigarette users transitioned to former
      smokers. After adjusting for covariates, cigarette smokers who initiated e
      cigarette use between waves and reported they used e-cigarettes daily at wave 2
      had 7.88 (95% CI 4.45 to 13.95) times the odds of 30-day cigarette cessation
      compared with non-users of e-cigarettes at wave 2. Cigarette smokers who began
      using e-cigarettes every day and did not achieve cessation had 5.70 (95% CI 3.47
      to 9.35) times the odds of reducing their average daily cigarette use by at least
      50% between waves 1 and 2 compared with e-cigarette non-users. CONCLUSIONS: Daily
      e-cigarette initiators were more likely to have quit smoking cigarettes or
      reduced use compared with non-users. However, less frequent e-cigarette use was
      not associated with cigarette cessation/reduction. These results suggest
      incorporating frequency of e-cigarette use is important for developing a more
      thorough understanding of the association between e-cigarette use and cigarette
      cessation.

PMID- 29574449
TI  - Price, tax and tobacco product substitution in Zambia.
AB  - BACKGROUND: In Zambia, the number of cigarette users is growing, and the lack of
      strong tax policies is likely an important cause. When adjusted for inflation,
      levels of tobacco tax have not changed since 2007. Moreover, roll-your-own (RYO)
      tobacco, a less-costly alternative to factory-made (FM) cigarettes, is highly
      prevalent. DATA AND METHODS: We modelled the probability of FM and RYO cigarette
      smoking using individual-level data obtained from the 2012 and 2014 waves of the
      International Tobacco Control (ITC) Zambia Survey. We used two estimation
      methods: the standard estimation method involving separate random effects probit
      models and a method involving a system of equations (incorporating bivariate
      seemingly unrelated random effects probit) to estimate price elasticities of FM
      and RYO cigarettes and their cross-price elasticities. RESULTS: The estimated
      price elasticities of smoking prevalence are -0.20 and -0.03 for FM and RYO
      cigarettes, respectively. FM and RYO are substitutes; that is, when the price of
      one of the products goes up, some smokers switch to the other product. The
      effects are stronger for substitution from FM to RYO than vice versa.
      CONCLUSIONS: This study affirms that increasing cigarette tax with corresponding
      price increases could significantly reduce cigarette use in Zambia. Furthermore,
      reducing between-product price differences would reduce substitution from FM to
      RYO. Since RYO use is associated with lower socioeconomic status, efforts to
      decrease RYO use, including through tax/price approaches and cessation
      assistance, would decrease health inequalities in Zambian society and reduce the
      negative economic consequences of tobacco use experienced by the poor.

PMID- 29574450
TI  - Put out to pasture: what is our duty of care to the retiring professional
      footballer? Promoting the concept of the 'exit health examination' (EHE).

PMID- 29574446
TI  - Comparison of incidence, rate and length of all-cause hospital admissions between
      adults with normoglycaemia, impaired fasting glucose and diabetes: a
      retrospective cohort study in Geelong, Australia.
AB  - OBJECTIVE: To determine whether adults with normoglycaemia, impaired fasting
      glucose (IFG) and diabetes differed according to the incidence, rate, length and
      primary reasons for hospital admission. DESIGN: Retrospective cohort study.
      SETTING: Barwon Statistical Division, Geelong, Australia. PARTICIPANTS: Cohort
      included 971 men and 924 women, aged 20+ years, participating in the Geelong
      Osteoporosis Study. Glycaemic status was assessed at cohort entry using fasting
      plasma glucose, use of antihyperglycaemic medication and/or self-report. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Primary outcome measure was any admission to the
      major tertiary public hospital in the study region over the follow-up period.
      Secondary outcome measures were admission rate and length (days). RESULTS: Over a
      median follow-up of 7.4 years (IQR 5.3-9.6), participants with diabetes, compared
      with those with normoglycaemia, were two times as likely to be hospitalised (OR
      2.07, 95% CI 1.42 to 3.02), had a higher admission rate (incidence rate ratio
      1.61, 95% CI 1.17 to 2.23) and longer hospital stay (third quartile difference
      7.7, 95% CI 1.3 to 14.1 and ninth decile difference 16.2, 95% CI 4.2 to 28.3).
      IFG group was similar to normoglycaemia for the incidence, rate and length of
      admission. Cardiovascular disease-related diagnoses were the most common primary
      reasons for hospitalisation across all glycaemic categories. CONCLUSIONS: Our
      results show increased incidence, rate and length of all-cause hospital admission
      in adults with diabetes as compared with normoglycaemia; however, we did not
      detect any associations for IFG. Interventions should focus on preventing IFG-to
      diabetes progression and reducing cardiovascular risk in IFG and diabetes.

PMID- 29574452
TI  - Correction: Persistent effects of playing football and associated (subconcussive)
      head trauma on brain structure and function: a systematic review of the
      literature.

PMID- 29574451
TI  - Patient demographic and surgical characteristics in anterior cruciate ligament
      reconstruction: a description of registries from six countries.
AB  - OBJECTIVE: Findings from individual anterior cruciate ligament reconstruction
      (ACLR) registry studies are impactful, but how various registries from different
      countries compare with different patient populations and surgical techniques has
      not been described. We sought to describe six ACLR registry cohorts to understand
      variation across countries. METHODS: Five European registries and one US registry
      participated. For each registry, all primary ACLR registered between registry
      establishment through 31December 2014 were identified. Descriptive statistics
      included frequencies, proportions, medians and IQRs. Revision incidence rates
      following primary ACLR were computed. RESULTS: 101 125 ACLR were included: 21 820
      in Denmark, 300 in Luxembourg, 17 556 in Norway, 30 422 in Sweden, 2972 in the UK
      and 28 055 in the US. In all six cohorts, males (range: 56.8%-72.4%) and soccer
      injuries (range: 14.1%-42.3%) were most common. European countries mostly used
      autografts (range: 93.7%-99.7%); allograft was most common in the US (39.9%).
      Interference screw was the most frequent femoral fixation in Luxembourg and the
      US (84.8% and 42.9%), and suspensory fixation was more frequent in the other
      countries (range: 43.9%-75.5%). Interference was the most frequent tibial
      fixation type in all six cohorts (range: 64.8%-98.2%). Three-year cumulative
      revision probabilities ranged from 2.8% to 3.7%. CONCLUSIONS: Similarities in
      patient demographics and injury activity were observed between all cohorts of
      ACLR. However, graft and fixation choices differed. Revision rates were low. This
      work, including >100 000 ACLR, is the most comprehensive international
      description of contemporary practice to date.

PMID- 29574453
TI  - Infographic. Achilles and patellar tendinopathy rehabilitation: strive to
      implement loading principles not recipes.

PMID- 29574454
TI  - Medial tibial stress syndrome: diagnosis, treatment and outcome assessment (PhD
      Academy Award).

PMID- 29574455
TI  - Meniscal root tears: a silent epidemic.

PMID- 29574456
TI  - Modeling Short QT Syndrome Using Human-Induced Pluripotent Stem Cell-Derived
      Cardiomyocytes.
AB  - BACKGROUND: Short QT syndrome (SQTS), a disorder associated with characteristic
      ECG QT-segment abbreviation, predisposes affected patients to sudden cardiac
      death. Despite some progress in assessing the organ-level pathophysiology and
      genetic changes of the disorder, the understanding of the human cellular
      phenotype and discovering of an optimal therapy has lagged because of a lack of
      appropriate human cellular models of the disorder. The objective of this study
      was to establish a cellular model of SQTS using human-induced pluripotent stem
      cell-derived cardiomyocytes (hiPSC-CMs). METHODS AND RESULTS: This study
      recruited 1 patient with short QT syndrome type 1 carrying a mutation (N588K) in
      KCNH2 as well as 2 healthy control subjects. We generated hiPSCs from their skin
      fibroblasts, and differentiated hiPSCs into cardiomyocytes (hiPSC-CMs) for
      physiological and pharmacological studies. The hiPSC-CMs from the patient showed
      increased rapidly activating delayed rectifier potassium channel current (IKr)
      density and shortened action potential duration compared with healthy control
      hiPSC-CMs. Furthermore, they demonstrated abnormal calcium transients and
      rhythmic activities. Carbachol increased the arrhythmic events in SQTS but not in
      control cells. Gene and protein expression profiling showed increased KCNH2
      expression in SQTS cells. Quinidine but not sotalol or metoprolol prolonged the
      action potential duration and abolished arrhythmic activity induced by carbachol.
      CONCLUSIONS: Patient-specific hiPSC-CMs are able to recapitulate single-cell
      phenotype features of SQTS and provide novel opportunities to further elucidate
      the cellular disease mechanism and test drug effects.

PMID- 29574457
TI  - Characteristics of Phrenic Nerve Injury During Pulmonary Vein Isolation Using a
      28-mm Second-Generation Cryoballoon and Short Freeze Strategy.
AB  - BACKGROUND: The reported incidence of phrenic nerve injury (PNI) varies owing to
      different definitions, balloon generations, balloon size, freezing regimen, and
      protective maneuvers. We evaluated the incidence, predictors, and outcome of PNI
      during cryoballoon pulmonary vein isolation in a large population. METHODS AND
      RESULTS: Five hundred fifty atrial fibrillation patients underwent pulmonary vein
      isolation using one 28-mm second-generation cryoballoon and single 3-minute
      freeze strategy under diaphragmatic compound motor action potential (CMAP)
      monitoring. A total of 34 (6.2%) patients experienced PNI during the right
      superior and inferior pulmonary vein ablation in 30 and 4 patients, respectively.
      Applications were interrupted using double-stop techniques after 136 [104-158]
      second applications, and a pulmonary vein isolation was already achieved in all
      but one case. The baseline CMAP amplitude and timing of deflation (CMAPdef) were
      0.75+/-0.30 and 0.17+/-0.17 mV, respectively. Persistent atrial fibrillation,
      larger right superior pulmonary vein ostia, and deeper balloon positions were
      associated with higher incidences of PNI. The CMAPdef predicted a PNI recovery
      delay, and the best cutoff value for predicting PNI recovery by the next day was
      0.20 mV (sensitivity 57.1%, specificity 100%). Among 6 patients undergoing second
      procedures 8.5 (6.7-15.0) months later, the right superior pulmonary vein was
      durable in 3 with >120 second applications. Despite active balloon deflation, no
      significant pulmonary vein stenosis was observed in 15 right superior pulmonary
      veins evaluated 6 (5-9) months later. No patients had symptoms, and the PNI
      recovered 1 day and 1 month postprocedure in 21 and 4 patients, respectively.
      CONCLUSIONS: PNI resulting from cryoballoon ablation was reversible. The double
      stop technique is safe, and immediate active deflation following a CMAP decrease
      appears to be essential for faster PNI recovery.

PMID- 29574458
TI  - Coffee Consumption and Coronary Artery Calcium Score: Cross-Sectional Results of
      ELSA-Brasil (Brazilian Longitudinal Study of Adult Health).
AB  - BACKGROUND: Available evidence for the relationship between coffee intake and
      subclinical atherosclerosis is limited and inconsistent. This study aimed to
      evaluate the association between coffee consumption and coronary artery calcium
      (CAC) in ELSA-Brasil (Brazilian Longitudinal Study of Adult Health). METHODS AND
      RESULTS: This cross-sectional study is based on baseline data from participants
      of the ELSA-Brasil cohort. Only participants living in Sao Paulo, Brazil, who
      underwent a CAC measurement (n=4426) were included. Coffee consumption was
      collected using a food frequency questionnaire. CAC was detected with computed
      tomography and expressed as Agatston units. CAC was further categorized as an
      Agatson score >=100 (CAC >=100). In multiple logistic regression analysis
      considering intake of coffee and smoking status interaction, significant inverse
      associations were observed between coffee consumption (>3 cups/d) and CAC>=100
      (odds ratio [OR]: 0.85 [95% confidence interval, 0.58-1.24] for <=1 cup/d; OR:
      0.73 [95% confidence interval, 0.51-1.05] for 1-3 cups/d; OR: 0.33 [95%
      confidence interval, 0.17-0.65] for >3 cups/d). Moreover, there was a
      statistically significant interaction effect for coffee consumption and smoking
      status (P=0.028 for interaction). After stratification by smoking status, the
      analysis revealed a lower OR of coronary calcification in never smokers drinking
      >3 cups/d (OR: 0.37 [95% confidence interval, 0.15-0.91]), whereas among current
      and former smokers, the intake of coffee was not significantly associated with
      coronary calcification. CONCLUSIONS: Habitual consumption of >3 cups/d of coffee
      decreased odds of subclinical atherosclerosis among never smokers. The
      consumption of coffee could exert a potential beneficial effect against coronary
      calcification, particularly in nonsmokers.

PMID- 29574459
TI  - Relation of Insulin Resistance to Longitudinal Changes in Left Ventricular
      Structure and Function in a General Population.
AB  - BACKGROUND: Population data on the longitudinal changes of left ventricular (LV)
      structure and function in relation to insulin resistance are sparse. Therefore,
      we assessed in a general population whether hyperinsulinemia predicts
      longitudinal changes in LV and arterial characteristics. METHODS AND RESULTS: In
      627 participants (mean age 50.7 years, 51.4% women), we assessed
      echocardiographic indexes of LV structure and function and carotid-femoral pulse
      wave velocity by applanation tonometry at baseline and after 4.7 years. We
      regressed longitudinal changes in these indexes on baseline insulin and its
      change during follow-up, and reported standardized effect sizes as a percentage
      of the SD of LV changes associated with a doubling of insulin. After adjustment,
      higher baseline insulin predicted a greater temporal increase in LV mass index
      (effect size: +15.1%) and E/e' ratio (+22.1%), and a greater decrease in e' peak
      and longitudinal strain (-11.2% to -17.1%). A greater increase in insulin during
      follow-up related to a greater increase in LV mass index (+10.7%) and decline in
      ejection fraction and longitudinal strain (-11.4% to -15.7%). Participants who
      became or remained insulin resistant during follow-up experienced worse changes
      in longitudinal strain, E/e', and LV mass index as compared with participants who
      did not develop or had improved insulin resistance over time (P<=0.033).
      Moreover, multivariable-adjusted increase in pulse wave velocity was higher in
      participants with diabetes mellitus than in participants without diabetes
      mellitus (+1.46 m/s versus +0.71 m/s; P=0.039). CONCLUSIONS: Hyperinsulinemia at
      baseline and during follow-up predicted worsening of LV function and remodeling
      over time. Our findings underline the importance of management of insulin
      resistance.

PMID- 29574460
TI  - The Unexpected Role of Calcium-Activated Potassium Channels: Limitation of NO
      Induced Arterial Relaxation.
AB  - BACKGROUND: Multiple studies have shown that an NO-induced activation of vascular
      smooth muscle BK channels contributes to the NO-evoked dilation in many blood
      vessels. In vivo, NO is released continuously. NO attenuates vessel constrictions
      and, therefore, exerts an anticontractile effect. It is unknown whether the
      anticontractile effect of continuously present NO is mediated by BK channels.
      METHODS AND RESULTS: This study tested the hypothesis that BK channels mediate
      the vasodilatory effect of continuously present NO. Experiments were performed on
      rat and mouse tail and rat saphenous arteries using isometric myography and FURA
      2 fluorimetry. Continuously present NO donors, as well as endogenous NO,
      attenuated methoxamine-induced vasoconstrictions. This effect was augmented in
      the presence of the BK channel blocker iberiotoxin. Moreover, the contractile
      effect of iberiotoxin was reduced in the presence of NO donors. The effect of the
      NO donor sodium nitroprusside was abolished by an NO scavenger and by a guanylyl
      cyclase inhibitor. In addition, the effect of sodium nitroprusside was reduced
      considerably by a protein kinase G inhibitor, but was not altered by inhibition
      of H2S generation. Sodium nitroprusside attenuated the intracellular calcium
      concentration response to methoxamine. Furthermore, sodium nitroprusside strongly
      reduced methoxamine-induced calcium influx, which depends entirely on L-type
      calcium channels. It did not affect methoxamine-induced calcium release.
      CONCLUSIONS: In summary, this study demonstrates the following: (1) continuously
      present NO evokes a strong anticontractile effect on rat and mouse arteries; (2)
      the iberiotoxin-induced augmentation of the effect of NO is associated with an NO
      induced reduction of the effect of iberiotoxin; and (3) NO evoked a reduction of
      calcium influx via L-type calcium channels.

PMID- 29574461
TI  - Police-Recorded Crime and Disparities in Obesity and Blood Pressure Status in
      Chicago.
AB  - BACKGROUND: The purpose of this study was to examine associations between several
      types of police-recorded crime (violent, nonviolent, and homicide) and
      cardiometabolic health (obesity and elevated blood pressure [BP]), and to
      determine if associations were modified by age and sex. METHODS AND RESULTS: We
      analyzed cross-sectional data (N=14 799 patients) from 3 primary care clinics at
      an academic medical center in Chicago, IL. Patient-level health data were
      obtained from the electronic health record (June 1, 2014-May 31, 2015), including
      body mass index and BP, and linked to the City of Chicago Police Data Portal.
      Geocoded crime counts were aggregated to census tract and calculated as the
      annual crime rate per 1000 population. Generalized linear mixed models were used
      to assess obesity and BP status as a function of crime rate quartile, controlling
      for patient, clinic, and neighborhood characteristics. Median violent crime rates
      in each quartile ranged from 15 to 84 per 1000 population. Median age was 56
      years (interquartile range, 38-72 years); 42% of patients were obese and 33% had
      elevated BP. Compared with patients living in the lowest quartile, patients
      living in the highest quartile for violent crime had 53% higher adjusted odds of
      obesity (95% confidence interval, 1.15-2.03) and 25% higher adjusted odds of
      elevated BP (95% confidence interval, 1.01-1.56). In subanalyses examining
      homicide, a relatively rare event, exposure was not associated with obesity and
      was inconsistently associated with elevated BP. CONCLUSIONS: In a densely
      populated, high-poverty region in Chicago, recurrent exposure to high rates of
      violent crime was consistently associated with obesity and elevated BP, but rare
      exposure to homicide was not.

PMID- 29574462
TI  - Remote Limb Ischemic Preconditioning Attenuates Cerebrovascular Depression During
      Sinusoidal Galvanic Vestibular Stimulation via alpha1-Adrenoceptor-Protein Kinase
      Cepsilon-Endothelial NO Synthase Pathway in Rats.
AB  - BACKGROUND: Vasovagal syncope (VVS) is characterized by hypotension and
      bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic
      preconditioning (RIPC) is well documented to provide cardio- and neuroprotection
      as well as to improve cerebral blood flow. We hypothesized that RIPC will provide
      protection against VVS-induced hypotension, bradycardia, and cerebral
      hypoperfusion. Second, because endothelial nitric oxide synthase has been
      reported as a mediator of cerebral blood flow control, we hypothesized that the
      mechanism by which RIPC primes the vasculature against VVS is via the alpha1
      adrenoceptor-protein kinase Cepsilon-endothelial nitric oxide synthase pathway.
      METHODS AND RESULTS: We utilized sinusoidal galvanic vestibular stimulation in
      rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure,
      heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular
      stimulation, as well as improving behavior during, and recovery after,
      stimulation. RIPC induced elevated serum norepinephrine, increased expression of
      brain alpha1-adrenoceptors, and reduced brain expression of norepinephrine
      transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1
      prevented RIPC protection of cerebral perfusion during sinusoidal galvanic
      vestibular stimulation. CONCLUSIONS: Taken together, this study indicates that
      RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease
      syncopal episodes, and reduce the injuries associated with syncopal falls.
      Furthermore, the alpha1-adrenoceptor-protein kinase Cepsilon-endothelial nitric
      oxide synthase pathway may be a therapeutic target for regulating changes in
      cerebral blood flow.

PMID- 29574463
TI  - Thoughtless design of the electronic health record drives overuse, but purposeful
      design can nudge improved patient care.

PMID- 29574464
TI  - Weekly variations in feelings of trust predict incident STI within a prospective
      cohort of adolescent women from a US city.
AB  - OBJECTIVES: Feelings of intimacy, perceptions of partner concurrency (PPC) and
      perceptions of risk for an STD (PRSTD) are meaningful and dynamic attributes of
      adolescent sexual relationships. Our objective was to examine whether variations
      in these STI-associated feelings and perceptions predicted incident Chlamydia
      trachomatis and/or Neisseriagonorrhoeae infection within a prospective cohort of
      urban adolescent women. METHODS: A cohort of clinic-recruited women aged 16-19
      completed daily surveys on feelings and risk perceptions about each current sex
      partner on a smartphone continuously for up to 18 months. Urine was tested for C.
      trachomatis and N. gonorrhoeae every 3 months. Daily responses were averaged
      across the week. As overall means for trust, closeness and commitment were high,
      data were coded to indicate any decrease in feelings from the previous week.
      PRSTD and PPC were reverse coded to indicate any increase from the previous week.
      An index was created to examine the cumulative effect of variation in these
      feelings and perceptions. Generalised linear models were used to account for
      correlation among repeated measures within relationships. RESULTS: For each week
      that there was a decrease in trust, there was a 45% increase in the risk of being
      infected with an STI at follow-up (relative risk (RR) 1.45, 95% CI 1.18 to 1.78,
      P=0.004). Neither a decrease in closeness or commitment, nor an increase in PRSTD
      or PPC was associated with an STI outcome. Cumulatively, the index measure
      indicated that a change in an additional feeling or perception over the week
      increased the odds of an STI by 14% (RR 1.14, 95% CI 1.02 to 1.29, P=0.026).
      CONCLUSIONS: A decrease in feelings of trust towards a main partner may be a more
      sensitive indicator of STI risk than PRSTD, PPC or commitment. The next
      generation of behavioural interventions for youth will need strategies to address
      feelings of intimacy within adolescent romantic relationships.

PMID- 29574465
TI  - Individual-level characteristics associated with oral HIV test acceptability
      among Peruvian men who have sex with men and transgender women: a cross-sectional
      study.
AB  - OBJECTIVES: Peruvian men who have sex with men (MSM) and transgender women (TGW)
      are highly vulnerable to HIV infection (HIV), but stigma, access issues and fear
      of venipuncture hamper testing. The oral HIV test-which uses oral fluids and
      provides results in 20 minutes-could reduce these barriers. The objective of this
      study was to determine the acceptability of the oral HIV test and the individual
      level factors associated with its acceptability among MSM and TGW. METHODS: We
      conducted a cross-sectional secondary analysis among Peruvian MSM and TGW
      attending a community-based health centre between February 2012 and February 2013
      to determine the individual-level factors associated with oral HIV test
      acceptability. RESULTS: Of 334 participants, 88% were MSM and 12% TGW. Overall,
      85% of participants indicated their acceptability of the oral HIV test.
      Acceptability was higher in MSM than TGW (85.7% vs 80.0%) but this difference was
      not significant. Factors associated with acceptability in MSM were: tertiary or
      higher education (prevalence ratio (PR)=1.18, 95% CI 1.06 to 1.32 and PR=1.16,
      95% CI 1.03 to 1.30, respectively); sex with drug use (PR=1.19, 95% CI 1.05 to
      1.36); believing that HIV is transmitted by saliva (PR=1.20, 95% CI 1.08 to
      1.33); and potential use of the oral test at home (PR=1.56, 95% CI 1.32 to 1.85).
      The only factor associated with lower acceptability was having had first anal
      intercourse between 14 and 19 years of age (PR=0.89, 95% CI 0.80 to 0.98).
      CONCLUSIONS: We identified the individual factors associated with oral HIV test
      acceptability among Peruvian MSM and TGW. Expanded use of the oral HIV test to
      increase testing rates among Peruvian MSM and TGW is recommended. TRIAL
      REGISTRATION NUMBER: NCT01387412, post-results.

PMID- 29574466
TI  - Clinical Significance of Ubiquitin Specific Protease 7 (USP7) in Predicting
      Prognosis of Hepatocellular Carcinoma and its Functional Mechanisms.
AB  - BACKGROUND Hepatocellular carcinoma (HCC) accounts for one of the most prevalent
      cancer types in the world. The ubiquitin specific protease 7 (USP7), a kind of
      deubiquitylating enzyme, has been reported to play multifaceted roles in
      different tumor types. The aim of this study was to investigate the expression
      and function of USP7 in HCC. MATERIAL AND METHODS Immunohistochemical staining
      and quantitative PCR were performed to explore the expression of USP7 in both HCC
      tissues and adjacent normal liver tissues. Chi-square test, univariate analysis,
      and multivariate analysis were conducted to statistically evaluate the clinical
      significance of USP7 in HCC. Proliferation, migration, and invasion capacities of
      HCC cells were assessed after overexpressing or silencing USP7. RESULTS Both the
      RNA and protein levels of USP7 were upregulated in HCC tissues compared to normal
      liver tissues. High expression of USP7 was correlated with advanced tumor stage
      and poor overall survival. Moreover, USP7 was identified as a novel independent
      prognostic factor for HCC patients. Cellular studies showed that USP7 could
      enhance the proliferation, migration, and invasion capacities of HCC cells,
      thereby promoting tumor progression. CONCLUSIONS High expression of USP7 is
      frequent in HCC tissues, which promotes tumor proliferation and invasion, and is
      correlated with a poor overall survival. Targeting USP7 may be a novel direction
      for the drug development of HCC therapy.

PMID- 29574467
TI  - Correlation Between Pigment Epithelium-Derived Factor (PEDF) level and Degree of
      Coronary Angiography and Severity of Coronary Artery Disease in a Chinese
      Population.
AB  - BACKGROUND The role of pigment epithelium-derived factor (PEDF) in protection of
      coronary artery disease (CAD) remains controversial. The aim of this study was to
      reassess the value of PEDF in predicting the severity and prognosis of newly
      diagnosed stable CAD in a Chinese population. MATERIAL AND METHODS Plasma PEDF
      levels were measured in 259 stable CAD patients undergoing coronary angiography
      and 116 age- and sex-matched healthy controls. The severity of coronary
      atherosclerosis was assessed using Gensini score. RESULTS PEDF levels were
      significantly lower in CAD patients than in healthy subjects (5.856+/-0.790 vs.
      6.658+/-1.070 MUg/ml, respectively, p<0.01). Stepwise regression analysis showed
      a negative correlation between PEDF levels and severity of CAD as quantified by
      Gensini score value (beta=-0.626, p<0.01). CONCLUSIONS Our study showed that
      plasma PEDF levels were significantly lower in CAD patients than in controls, and
      the plasma PEDF levels may be used as a potential predicator for coronary
      severity.

PMID- 29574468
TI  - Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati
      Syndrome.
AB  - BACKGROUND Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic
      condition that was first described in 1983. Since its original description,
      approximately 50 cases have been reported with various clinical signs and
      symptoms. Characteristics include progressive neurologic deterioration with
      extrapyramidal involvement and polyendocrinopathy most notable for hypogonadism
      starting in early adolescence. Clinical presentation is variable, and a subset of
      patients may have additional features, such as premature aging, alopecia,
      distinctive facial features, cognitive impairment, or deafness. CASE REPORT We
      illustrate the phenotypic variability of 5 patients with WSS due to the
      previously reported homozygous single nucleotide deletion c.436delC in the DCAF17
      gene, identified in 2008. Despite identical genetic alteration, our 5 patients
      had various clinical features among them and compared with previously reported
      cases with the same pathogenic mutation. CONCLUSIONS The phenotypic variability
      of WSS due to c.436delC founder mutation may have a wider range than previously
      recognized.

PMID- 29574469
TI  - Adverse effect of the disturbances of glycemia and insulimemia on model PC12
      cells - preliminary report.
AB  - BACKGROUND: One of the most important worldwide health problems of the 21st
      century is an increasing incidence of diabetes and insulin resistance. Morover,
      it is indicated that both these disturbances are connected with an increased
      incidence of Alzheimer's Disease. The literature data indicate that not only
      disturbed glucose concentration, especially hyperglycemia, is a crucial factor of
      the development of dementia but those data also emphasize that hyperphysiological
      concentrations of insulin and insulin resistance of brain tissue is an
      increasingly significant factor. The aim of this study was to evaluate the
      influence of glucose and insulin concentration reached in human carbohydrate
      metabolism disorders such as i.e. impaired fasting glucose, impaired glucose
      tolerance and diabetes state as well as averageand high degree hyperinsulinemia,
      on the survival of PC12 cell line. MATERIAL AND METHODS: Because of the close
      association indicated between diabetes and neurodegenerative diseases, in the
      experiment we used PC12 cell line derived from a transplantable rat
      pheochromocytoma, commonly used as an neurotoxicity and neuroprotection model.
      These cells were incubated in RPMI 1640 with addition of fetal bovine serum,
      horse serum, antibiotics and appropriate concentrations of glucose(from 84 to 240
      mg/mL) and insulin(0.5 to 7 mg/mL) at 37 degrees C in a humidified atmosphere
      containing 5% of CO2for 24 h and 48 h. Cell viability was expressed as a
      percentage of survival (PS [%]) against the negative control after MTT assay
      execution. RESULTS: The highest mortality was demonstrated for PC12 lines
      incubated for 24 h with the glucose level reflecting the condition of diabetes
      mellitus (DM), while after an incubation period of 48 h, the highest mortality
      was demonstrated for the incubation with insulin concentration corresponding to
      high levels of hyperinsulinemia (HH). Conclutions. The results suggest the
      greater susceptibility of PC12 cells to extended hyperinsulinaemia incubation
      than hyperglycemia,which indicates the increasing importance of insulin disorders
      in the induction of cell death.The results demonstrated in our experiment are
      particularly important for the development of a study model for testing the
      substances with hypoglycaemic, hypoinsulinemic and neuroprotective action.

PMID- 29574470
TI  - Epidemiological aspects of obesity and systemic hypertension amongschool children
      of Western Ukraine.
AB  - INTRODUCTION: Systemic hypertension (SH) is a major long-term health condition
      and is the leading cause of premature death among adults throughout the world,
      including developed, developing, and lesser developed countries.In recent years
      there has been a progressive increase in SH among children and adolescents.
      Epidemiological studies demonstrated an overall increase in the prevalence of
      hypertension. SH is rarely recorded isolated and is often combined with obesity
      or the metabolic syndrome. AIM OF THE STUDY: The aim of our research was to study
      the prevalence of overweight, obesity, and systemic hypertension in Ukrainian
      school children aged 10-16 years. MATERIAL AND METHODS: 540 pupils of two
      secondary schools in the city of Ternopil, aged 10-16 years, were involved. Blood
      pressure was measured under standard conditions using the standard technique. To
      assess the physical development of each child, indicators of body weight, height,
      waist circumferences and body mass index were compared with percentile tables.
      RESULTS: The study has demonstrated that the prevalence of overweight is 11.1%
      and obesity 4.8% among pupils of Ternopil. The elevated blood pressure was found
      in 50 % of overweight or obese pupils. SH was found in 13.3% of children (11.8%
      of girls and 15.1% of boys), where pre-hypertension (p<0,01) and SH 1st (p<0,01)
      stages were observed twice as often in boys than in girls, and normal BP was
      recorded less frequently (p<0,01). CONCLUSIONS: The boys are three times more
      often obese than girls and 1.4 times more often overweight. The blood pressure is
      directly correlated with increased BMI, waist and hip circumference in the
      examined children. The abdominal obesity is a predictor of hypertension in
      adolescents. The result of the present study has demonstrated the real
      epidemiology of obesity and systemic hypertension in children and adolescents,
      and should motivate family doctors and paediatricians to prevent this pathology
      in Ukraine.

PMID- 29574471
TI  - Assessing the knowledge of the consequences of uncontrolled diabetesin pregnancy
      and its effects on fetal development, among femaleadolescents with type 1
      diabetes.
AB  - INTRODUCTION: Two forms of diabetes can be distinguished during pregnancy:
      gestational diabetes and pregestational diabetes, which exists prior to
      pregnancy. In young women, the most common form of pregestational diabetes is
      type 1 diabetes (T1D). Regarding the decreasing age of sexual initiation and
      health risks for the mother and child related to hyperglycemia, it is essential
      that adolescents with T1D possess proper knowledge of pregnancy planning and
      diabetes management in case of pregnancy. Preconception counseling in adolescent
      patients with T1D remains a challenge for the whole therapeutic team. AIM OF THE
      STUDY: Assessing the awareness of consequences of uncontrolled diabetes on the
      course of pregnancy and fetal development among patients with T1D. MATERIAL AND
      METHODS: The study was carried out in the group of 70 patients with T1D, aaged 15
      18 years. The survey was consisted of 25 questions regarding health status,
      lifestyle, the knowledge of self-management of diabetes and the impact of
      diabetes on pregnancy and fetal development. Respondents were asked to indicate
      the sources of information from which they had gianed knowledge about the
      aforesaid issues. The data obtained were statistically analyzed. RESULTS: 20%
      (n=14) of respondents declared sexual activity. In the group of sexually active
      patients, in 50% (n=7) last HbA1c level, reported by subjects, was between 7.5
      9%, and in 21.4% (n=3) >9%. The patients were aware of the consequences of
      uncontrolled diabetes on fetal development, however their knowledge was
      unsatisfactory. Surveyed adolescents indicated metabolic disorders (61.4 %,
      n=43), central nervous system malformations (55.7%, n=39) and heart defects
      (47.1%, n=33) as the most frequent complications. The respondents gathered
      knowledge mainly from a diabetologist (40%, n=28) and the Internet (40%, n=28).
      The majority of patients stated that preconception care should be provided by a
      diabetologist (88.6%, n=62) or a gynecologist (70%, n=49). CONCLUSION: In spite
      of continuous diabetes care, adolescents with T1D do not possess sufficient
      knowledge regarding the consequences of hyperglycemia during pregnancy. This
      study has emphasized the need for including reproductive health issues in
      diabetes education addressed to adolescent patients.

PMID- 29574472
TI  - [Effects of oncological therapy on bone disorders].
AB  - Due to increasing incidence of cancer disease and the searching for new,
      aggressive methods of therapy, more attention is focusing on applied treatment
      consequences. The specificity of oncological drugs allows to destroy cancer
      cells, simultaneously destroying and disrupting the functioning of healthy
      tissues. Side effects concern infertility, urolotoxicity, nephrotoxicity,
      neurotoxicity or bone marrow suppression. Chemotherapy can also be affected on
      physiological function of movement system and the skeleton construction. Mineral
      status disorders and skeletal changes lead to secondary forms of osteopenia and
      osteoporosis and refer oncological patients of any age. The main cause of these
      conditions is an imbalance between osteoclast and osteoblast activity, occurring
      as a result of drug interactions, parathyroid hormone-like proteins or
      interleukins. In addition to the direct effect on bone tissue, disorders in its
      construction and metabolism are also manifested as a consequence of hypogonadism.
      The sexual hormones at normal level can inhibit process of bone destruction,
      increase parathormone level, stimulate active vitamin D3 formation and intestinal
      calcium absorption. The deficiency of estrogens and androgens indirectly leads to
      disorder of bone metabolism and homeostasis. Symptoms such as musculoskeletal
      pain and fractures appear in the late stage of degeneration. Moreover, the
      appropriate selection of therapy and dosage, compatible with the patient's age
      and condition are crucial for treatment. Early bone loss should be prevented by
      supplementing with calcium, vitamin D3, hormone replacement therapy or
      bisphosphonates. The physical activity and proper diet are important as well. The
      aim of the study was to characterize the most common oncological treatment
      regimens, considering the long-term side effect of applied therapy and its
      influence on the skeletal mineralization and trace element profile. Based on the
      mechanism of drug action, the disorders observed after pharmacotherapy were
      described. The processes leading to bone's composition changes were discussed and
      prevention of their occurrence were estimated.

PMID- 29574473
TI  - Metabolic disorders in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex disease. Depending on the used
      criteria the prevalence of PCOS ranges from 6 to 20%. It is necessary to exclude
      diseases leading to androgen excess. The participation of genetic and
      environmental factors is considered in the etiology of PCOS development. The
      highest rate of incidence of PCOS is assessed in girls who were born SGA and
      developed premature adrenarche later in life.The free androgen index (FAI) is
      concerned as the most sensitive marker of hyperandrogenaemia in PCOS although
      insulin resistance, anti-Mullerian hormone (AMH),and deficiency of vitamin D may
      intensify metabolic disturbances. The ultrasound criteria used in adolescent
      patients prefer the estimation of the ovarian volume or the ratio of ovarian
      stroma to total ovary, rather than the number of ovarian follicles. PCOS is
      connected with different metabolic disorders. Post-binding defect in signal
      transduction is responsible for insulin resistance. This defect results from an
      impaired activity of the kinase receptor. Moreover, the adipose tissue of PCOS
      women differs substantially from the tissue of the others according to morphology
      and function. The adipocytes produce lower amounts of adiponectin, which is an
      insulin-sensitizing agent. Dyspidemia with high triglycerides and low high
      density lipoprotein cholesterol concentrations is frequently noticed. Cardio
      metabolic risk factors, insulin resistance, and endothelial dysfunction accompany
      PCOS from the very beginning. Oxidative stress plays a role as a link among
      systemic inflammation and dysfunction of endothelial cells and abnormal thecal
      cell action. The treatment efforts in PCOS depend on the patient's main problems.
      Modification of diet and lifestyle is the most important recommended advice to
      each woman independent of age and weight.

PMID- 29574474
TI  - Thyroid hormone resistance syndrome - own experiences.
AB  - Thyroid hormone resistance syndrome, also known as Refetoff syndrome, is a rare
      disease associated with decreased reaction of body tissues to thyroid hormones
      (TH). Patients with Refetoff syndrome tend to have elevated free TH
      concentrations and normal or inadequately elevated TSH (caused by thyrotropic
      cells in the pituitary gland insensitivity to TH). The cause of the disease is
      the mutation in TR-beta receptor gene. Depending on the clinical presentation
      generalised and pituitary resistance to TH are described. The syndrome is often
      misdiagnosed as hyperthyroidism and unnecessarily treated with anti-thyroid
      drugs. Some patients receive l-thyroxine treatment for apparent hypothyroidism.
      In this report, three patients are presented with a long history in our Clinic
      and Outpatient Clinic.

PMID- 29574475
TI  - Is growth without IGF1 possible? A case report.
AB  - According to the growth hormone - insulin-like growth factor 1 axis (GH/IGF1
      axis) theory, the actions of GH on promoting growth are mediated by IGF1. In the
      blood, IGF1, insulin-like growth factor 1 binding protein 3 (IGFBP3) and acid
      labile subunit (ALS) form ternary complexes, hence the accumulation of IGF1. We
      report a case of 10-year-old male with short stature due to GH deficiency
      diagnosed with hypopituitarism. Therapy with recombinant human GH (rhGH) was
      initiated at 11 years and 4 months. After twenty three months on treatment
      clinical effects were as follows: increase in the patient's height by 19.2 cm
      (initial height 12.4 cm vs. 140.6 cm; hSDS -4.35 vs. -2.7; predicted adult height
      176 cm vs. 182 cm, respectively). Despite good clinical response to the therapy,
      serum levels of IGF1 and IGFBP3 remained diminished: IGF1 - 28 ng/ml initially,
      vs. 23 ng/ml 19 months on therapy and IGFBP3 - 1116 ng/ml initially, vs. 1888
      ng/ml after 11 months on therapy. We attempt to justify this phenomenon by
      reconsidering the IGF1-independent GH actions, assessing the endocrine role of
      hepatic IGF1 in comparison to the autocrine/paracrine role of its bone tissue
      fraction, and evaluating the functions of ALS. The exact explanation for the
      positive response to rhGH treatment without the expected increase in IGF1 in our
      patient remains unknown. Serum levels of IGF1 and IGFBP3 seem not always to be
      reliable markers of the response to rhGH treatment in GH-deficient patients.

PMID- 29574476
TI  - Exposure to traffic noise and air pollution and risk for febrile seizure: a
      cohort study.
AB  - Objectives Exposure to traffic noise and air pollution is suspected to increase
      susceptibility to viral infections - the main triggering factor for febrile
      seizures. No studies have examined these two exposures in relation to febrile
      seizures. We aimed to investigate whether exposure to road traffic noise and air
      pollution are associated with risk of febrile seizures in childhood. Methods From
      our study base of 51 465 singletons from a national birth cohort, we identified
      2175 cases with febrile seizures using a nationwide registry. Residential address
      history from conception to six years of age were found in national registers, and
      road traffic noise (L den) and air pollution (NO 2) were modeled for all
      addresses. Analyses were done using Cox proportional hazard model with adjustment
      for potential confounders, including mutual exposure adjustment. Results An
      interquartile range (IQR) increase in childhood exposure to road traffic noise
      and air pollution was associated with an 11% [incidence rate ratio (IRR) 1.11,
      95% confidence interval (CI) 1.04-1.19) and 5% (IRR 1.05, 95% CI 1.02-1.07)
      higher risk for febrile seizures, respectively, after adjustment for potential
      confounders. Weaker tendencies were seen for pregnancy exposure. In models with
      mutual exposure adjustment, the estimates were slightly lower, with IRR of 1.08
      (95% CI 1.00-1.16) and 1.03 (95% CI 0.99-1.06) per IQR increase in childhood
      exposure to road traffic noise and air pollution, respectively. Conclusions This
      study suggests that residential exposure to road traffic noise and air pollution
      is associated with higher risk for febrile seizures.

PMID- 29574477
TI  - Is perception of safety climate a relevant predictor for occupational accidents?
      Prospective cohort study among blue-collar workers.
AB  - Objectives The capability of safety climate to predict accidents has been the
      target of widespread debate in occupational health and safety research. The
      objective of this prospective cohort study was to employ a shortened five-item
      safety climate survey to investigate whether safety climate reports in 2012 are
      predictive for accidents reported within the last 12 months in 2014. Methods In
      both 2012 and 2014, 3864 blue-collar workers answered the Danish Working
      Environment and Health Cohort Study. Logistic regression was used to study the
      association [odds ratio (OR)] of reporting a work-related accident (yes/no) with
      more than one day of sickness absence (outcome) within the last 12 months in 2014
      with the number of safety climate problems (predictor). The analyses were
      cumulatively adjusted for age, gender (model 1), socioeconomic class,
      occupational group, lifestyle (model 2), and previous accidents in 2012 (model
      3). Results Of the safety climate problems reported in 2012, 1017 (28%)
      participants reported one problem, 357 (10%) reported two and 614 (17%) reported
      three or more problems. Using the number of safety climate problems as a
      continuous variable, all models showed a dose-response relationship between
      number of safety climate problems in 2012 and at least one accident in 2014
      (trend-test, P<0.001). Compared to participants with no safety climate problems,
      participants reporting two safety climate problems in 2012 had a higher risk for
      reporting an accident in 2014 [OR 1.84, 95% confidence interval (CI) 1.22-2.77],
      and the risk was higher for participants reporting three or more safety problems
      (OR 2.22, 95% CI 1.60-3.09). Conclusions A higher number of safety climate
      problems progressively increased the OR for reporting at least one accident
      within the last 12 months at the two-year follow-up. The five-item safety climate
      survey is a simple and important tool that can be used as part of risk assessment
      in blue-collar workplaces.

PMID- 29574478
TI  - Correction to: Draft Genome Sequence of Cyclohexylamine-Degrading Strain
      Acinetobacter sp. YT-02 Isolated.
AB  - The original version of this article unfortunately contained a mistake in the
      Fig. S1 of supplementary material. It is corrected with this erratum.

PMID- 29574479
TI  - Correction to: Coordination of muscles to control the footpath during over-ground
      walking in neurologically intact individuals and stroke survivors.
AB  - In the original publication of the article, the corrections for the typographical
      errors in the equations for variance that affects the footpath (VORT) and the
      total variance (VTOT) should be as following.

PMID- 29574480
TI  - Author Correction: PKC-dependent phosphorylation of Munc18a at Ser313 in
      activated RBL-2H3 cells.
AB  - Acknowledgements This work was supported by the University of Southern
      Mississippi Development Grant DE01475, the National Institute of Allergy and
      Infectious Diseases Grant 1R15AI133430-01, and by the Mississippi INBRE, which
      was funded by an Institutional Development Award (IDeA) from NIGMS under Grant
      no. P20GM103476.

PMID- 29574481
TI  - Commentary on: Comparison of inflammatory urine markers in patients with
      interstitial cystitis and overactive bladder.

PMID- 29574482
TI  - The effect of pelvic floor muscle training and intravaginal electrical
      stimulation on urinary incontinence in women with incomplete spinal cord injury:
      an investigator-blinded parallel randomized clinical trial.
AB  - INTRODUCTION AND HYPOTHESIS: Urinary incontinence is a prevalent problem in women
      with spinal cord injury. The aim of this study was to examine the effect of
      pelvic floor muscle training (PFMT) alone and combined with intravaginal
      electrical stimulation (IVES) on urinary incontinence in women with incomplete
      spinal cord injury. METHODS: In this investigator-blinded randomized clinical
      trial, we recruited women aged 18-75 with incomplete spinal cord injury and
      urinary incontinence from a single spinal cord injury clinic in Denmark. Women
      were randomly assigned to either PFMT or PFMT combined with IVES daily at home
      for 12 weeks. All women were trained by a physiotherapist using vaginal palpation
      and electromyography biofeedback. Outcome measures were recorded at baseline
      (week 0), post-intervention (week 12) and follow-up (week 24) and included change
      in the total score on the International Consultation on Incontinence
      Questionnaire urinary incontinence short form (ICIQ-UI-SF) and daily episodes of
      urinary incontinence. RESULTS: From 27 April 2015-9 September 2016, we randomly
      assigned 36 women (17 in the PFMT group and 19 in the PFMT+IVES group); 27
      completed the interventions (13 in the PFMT group and 14 in the PFMT+IVES group).
      The results showed no difference between the groups on ICIQ-UI-SF or episodes of
      urinary incontinence at 12 and 24 weeks. Only the PFMT group had a significant
      change from baseline on ICIQ-UI-SF [-2.4 (95% CI -4.3--0.5), p = 0.018] and daily
      episodes of urinary incontinence [-0.4 (95% CI -0.8--0.1), p = 0.026] at 12
      weeks. CONCLUSIONS: PFMT+IVES is not superior to PFMT alone in reducing urinary
      incontinence in women with incomplete spinal cord injury.

PMID- 29574483
TI  - Prevalence of lower urinary tract symptoms and social determinants in primary
      care users in Brazil.
AB  - INTRODUCTION AND HYPOTHESIS: Although lower urinary tract symptoms (LUTS) have
      considerable clinical relevance, few propose evaluating its association with
      social conditions. Our study aimed to evaluate LUTS prevalence in primary care
      and its association with the social determinants of health (SDH). METHODS: This
      is a cross-sectional study conducted with 322 females in the period of June to
      October 2016 that carried out consultations and screening to prevent
      gynecological cancer in a primary care unit. RESULTS: The ages ranged from 18 to
      85 years (M = 40.53). Storage symptoms had a higher overall prevalence (64.6%),
      highlighting nocturia (n = 186, 57.8%) and urinary incontinence (n = 120, 37.3%).
      Storage symptoms were associated with three layers of SDH. The voiding and
      postmicturition symptoms were only related to operative vaginal delivery.
      CONCLUSIONS: The findings of this study suggest a relationship between SDH and
      LUTS. It is important to emphasize that the results not only imply a causal
      relationship, but also point to the social inequalities existing at a population
      level.

PMID- 29574484
TI  - The effect of solifenacin on postvoid dribbling in women: results of a
      randomized, double-blind placebo-controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: To determine the effectiveness of the muscarinic
      receptor antagonist solifenacin (VESIcare(r)) in the treatment of postvoid
      dribbling (PVD). METHODS: We carried out a multicenter, 12-week, double-blind,
      randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a
      total of 118 women (age 18-89 years) with PVD at least twice/weekly, were
      randomized to receive solifenacin (5 mg; n = 58) or placebo (n = 60) once daily.
      The primary outcome was the percentage reduction in PVD episodes. Secondary
      outcomes included the percentage of patients with >=50% reduction in PVD episodes
      and changes in quality of life. RESULTS: There were no differences in either the
      primary or secondary outcome variables. Subgroup analysis, based on those with
      more severe disease (>10 PVD episodes/week), showed a greater and significant
      percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p
      = 0.035) and a higher percentage of patients showing >=50% reduction in the
      frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p = 0.0476). A
      significant solifenacin effect occurred at week 2 and continued through week 12
      for the subgroup. For solifenacin, PVD reduction was the same for the entire
      cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup,
      declining from 42% to 32%. CONCLUSION: There were no differences in PVD outcomes
      between the solifenacin and placebo groups. Solifenacin may play a role in
      treating women with the most severe symptoms. Because of the powerful placebo
      response seen in this study, behavior-based interventions may be useful for
      treating PVD.

PMID- 29574485
TI  - Vaginal hysterectomy with apical fixation and anterior vaginal wall repair for
      prolapse: surgical technique and medium-term results.
AB  - INTRODUCTION AND HYPOTHESIS: Stabilization of the vaginal apex (level 1) is an
      important component of operations to correct pelvic organ prolapse (POP). We
      report functional and anatomical results and patient-reported outcomes of our
      technique of vaginal vault fixation at the time of vaginal hysterectomy. METHODS:
      One hundred and nine patients-mean 69 years, range 50.4-83.8; body mass index
      (BMI) 26.3, range 17.7-39.5-with symptomatic stage 2-3 uterine prolapse combined
      with stage 3-4 cystocele underwent vaginal hysterectomy with anterior vaginal
      wall repair; the apex was formed with high closure of the peritoneum and
      incorporation of the uterosacral and round ligaments. Only absorbable sutures
      were used. Follow-up included clinical examination with Pelvic Organ Prolapse
      Quantification system (POP-Q) scoring, introital ultrasonography, quality of life
      (QoL) Likert scale, and the German Pelvic Floor Questionnaire. RESULTS: Seventy
      patients (64%) were available for a follow-up after a mean of 2.8 years (range,
      1.6-4.2). At follow-up, point C was stage 0 in 55 (78.6%) women and stage 1 in 15
      (21.4%). The anterior vaginal wall was stage 0 or 1 in 35 (50%), stage 2 (no
      cystocele beyond the hymen) in 34 (49%), and stage 3 in 1 (1.4%). Vaginal length
      (VL) was 9 cm. Four women (4%) were reoperated for prolapse: two for recurrent
      anterior compartment prolapse and two for de novo rectocele. Postvoid residuals
      >150 ml were seen in 21(30%) patients preoperatively and resolved postoperatively
      in 20. Urgency occurred in nine (13%), stress urinary incontinence (SUI) in ten
      (14%), and nocturia in 19 (27%). No patient had discomfort at the vaginal vault
      and 62 patients (87%) reported improved QoL, which did not correlate with
      anatomical results. Cystocele >= 2 degrees  at follow-up was associated with BMI
      >25 (p = 0.03). CONCLUSIONS: Our surgical technique without permanent material
      offers good apical support and functional and subjective results. Anatomical
      improvement was achieved in all cases of cystocele repair. Recurrent cystoceles
      are often asymptomatic.

PMID- 29574486
TI  - DELLA proteins negatively regulate dark-induced senescence and chlorophyll
      degradation in Arabidopsis through interaction with the transcription factor
      WRKY6.
AB  - KEY MESSAGE: DELLA proteins' negative regulation of dark-induced senescence and
      chlorophyll degradation in Arabidopsis is through interaction with WRKY6 and thus
      repression of its transcriptional activities on senescence-related genes.
      Senescence is an intricate and highly orchestrated process regulated by numerous
      endogenous and environmental signals. Gibberellins (GAs) and their signaling
      components DELLA proteins have been known to participate in the regulation of
      senescence. However, the mechanism of the GA-DELLA system involved in the
      senescence process remains largely unclear. Darkness is a known environmental
      factor that induces plant senescence. In this study, exogenous GA3 (an active
      form of GA) accelerated but paclobutrazol (a specific GA biosynthesis inhibitor)
      retarded dark-induced leaf yellowing in Arabidopsis. Moreover, the dark-triggered
      decrease in chlorophyll content, increase in cell membrane leakage, and
      upregulation of senescence-associated genes were notably impaired in both
      endogenous GA-decreased mutants ga3ox1/ga3ox2 and ga20ox1/ga20ox2 compared with
      those in wild-type Col-0. These effects of darkness were enhanced in the
      quintuple mutant of DELLA genes gai-t6/rga-t2/rgl1-1/rgl2-1/rgl3-1 and conversely
      attenuated in the gain-of-function mutant gai and transgenic plant 35S::TAP
      RGAd17 compared with wild-type Ler. Subsequently, RGA interacted with the
      transcription factor WRKY6 in a yeast two-hybrid assay, as confirmed by
      bimolecular fluorescence complementation and pull-down analyses. In addition,
      mutation and overexpression of WRKY6 retarded and accelerated dark-induced
      senescence, respectively. Furthermore, transient expression assays in Arabidopsis
      protoplasts indicated that RGA and GAI weakened the transcriptional activities of
      WRKY6 on its downstream senescence-related genes, including SAG13 and SGR. Taken
      together, these results suggest that GAs positively and DELLAs negatively
      regulate dark-induced senescence and chlorophyll degradation in Arabidopsis.
      DELLAs function in this process, at least in part, by interacting with WRKY6.

PMID- 29574487
TI  - Isolation, expression, and functional analysis of developmentally regulated
      plasma membrane polypeptide 1 (DREPP1) in Sporobolus virginicus grown under
      alkali salt stress.
AB  - The plant specific DREPP proteins have been shown to bind Ca2+ and regulate the N
      myristoylation signaling and microtubule polymerization in Arabidopsis thaliana.
      The information about DREPP proteins in other plants is, however, scarce. In the
      present study, we isolated the DREPP gene from a halophytic grass, Sporobolus
      virginicus, and tested whether the gene was involved in alkaline salt stress
      responses. The SvDREPP1 was cloned from S. virginicus by RACE methods. The
      isolated gene showed high homology to DREPP homologs from C4 grasses, Setaria
      italica, and Panicum hallii as well as rice (OsDREPP1). The encoded protein
      contained 202 amino acid residues. It was expressed in E. coli, and its
      biochemical properties were studied. It was observed that SvDREPP1 was not only
      Ca2+-binding protein, but also bind to calmodulin and microtubules. The SvDREPP1
      mRNA expression in plants grown under alkaline salt stress was upregulated by 3.5
      times over the control in leaf tissues after 48-h treatment, whereas it was
      increased for 6.0 times in the root tissues at 36 h. The data suggests the
      importance of SvDREPP1 in regulating alkali salt stress responses in the leaf
      tissues.

PMID- 29574488
TI  - Simpson-Golabi-Behmel syndrome human adipocytes reveal a changing phenotype
      throughout differentiation.
AB  - The Simpson-Golabi-Behmel syndrome (SGBS) cell strain is widely considered to be
      a representative in vitro model of human subcutaneous white pre-adipocytes. These
      cells achieve a transient expression of classical brown markers, such as
      uncoupling protein 1, peaking at day 14 of differentiation and decreasing
      thereafter. Adipocyte browning process involves dynamic changes in lipid droplet
      (LD) dimension, in mitochondria morphology, and in the expression of brown
      specific marker genes. This study analyzes SGBS transient phenotypic
      transformation by quantifying the heterogeneity of LDs, mitochondrial dynamics,
      and a panel of genes involved in adipocyte differentiation and browning. LDs at
      21 days of differentiation were larger than in the previous stages, without any
      change in the number per cell. The expression of genes such as peroxisome
      peroxisome proliferator-activated receptor gamma, leptin, and lipase E
      significantly raised from 0 to 21 days. Adiponectin was significantly upregulated
      at 14 days of differentiation. Brown-specific marker PR domain containing 16 was
      highly expressed at D0. The variability of mitochondrial shape and
      interconnectivity reflects differences in the relative rates of fusion and
      fission, resulting in a significant shift from a networked shape at D7 to a
      fragmented and swollen one at D14 and D21. The transient phenotype experienced by
      this cellular model should be considered whether used in studies involving the
      stimulation of adipocyte browning and could be an interesting human model to
      further elucidate the browning process in the absence of any stimulation.

PMID- 29574489
TI  - Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers:
      an observational cohort study.
AB  - BACKGROUND: Ongoing discussion about the safety of renin-angiotensin inhibitors
      in the first trimester and limited data on pregnancy outcomes after exposure to
      angiotensin AT1 receptor blockers (ARBs). METHODS: Observational cohort study
      compares outcomes of 215 prospectively ascertained pregnancies with first
      trimester exposure to ARBs with 642 non-hypertensive pregnancies. RESULTS: The
      rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in
      the comparison group (17/570, 3%), but not significantly increased (ORadj 1.9,
      95% CI 0.7-4.9). There was no distinct pattern of anomalies among infants with
      birth defects. The risk of spontaneous abortions was not increased (HRadj 0.9,
      95% CI 0.5-1.6), although the cumulative incidence was in the upper normal range
      (0.22, 95% CI 0.15-0.32). Higher rates of prematurity (ORadj 3.0; 95% CI 1.7-5.1)
      and a reduced birth weight after adjustment for sex and gestational age were
      observed. There was no evidence for an increased risk for major birth defects,
      spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB
      exposed hypertensive women to hypertensive women without ARB exposure during the
      first trimester. CONCLUSION: Our study supports the hypothesis that ARBs are not
      major teratogens. Patients inadvertently exposed to ARBs during the early
      pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid
      ARBs. In selected cases, ARBs might be continued under careful monitoring of
      menstrual cycle and discontinued as soon as pregnancy is recognized.

PMID- 29574490
TI  - Kinetic and thermodynamic studies on the enzymatic synthesis of wax ester
      catalyzed by lipase immobilized on glutaraldehyde-activated rice husk particles.
AB  - Commercial lipase from Thermomyces lanuginosus has been immobilized on
      glutaraldehyde-activated rice husk particles via covalent attachment. It was
      reached maximum immobilized protein concentration of 27.5 +/- 1.8 mg g-1 of dry
      support using the initial protein loading of 40 mg g-1 of support. The
      immobilized biocatalyst was used to synthesize cetyl oleate (wax ester) via
      direct esterification of oleic acid and cetyl alcohol. The influence of relevant
      factors on ester synthesis, such as reaction temperature, biocatalyst
      concentration, presence or lack of hydrophobic organic solvents, acid:alcohol
      molar ratio, and reaction time has been evaluated. The experimental data were
      well fitted to a second-order reversible kinetic model to determine apparent
      kinetic constants. Thermodynamic studies have revealed that the reaction was a
      spontaneous and endothermic process. Under optimal experimental conditions, it
      was observed maximum ester conversion of 90.2 +/- 0.6% in 9 h of reaction time in
      hexane medium using 1 M of each reactant (cetyl alcohol and oleic acid), at 50 
      degrees C and biocatalyst concentration of 15% m/v of reaction mixture. Similar
      conversion (91.5 +/- 0.8%) in a solvent-free system was also obtained within 24 h
      of reaction. The biocatalyst retained 85% of its initial activity after 12 cycles
      within 9 h of reaction in hexane medium. The physicochemical properties of
      purified ester have been determined in accordance with ASTM standards. The
      results indicate that the prepared biocatalyst has great potential for wax ester
      synthesis due to its satisfactory catalytic activity and operational stability.

PMID- 29574491
TI  - The role of myeloid derived suppressor cells in mycosis fungoides.

PMID- 29574492
TI  - The anterior knee: normal variants, common pathologies, and diagnostic pitfalls
      on MRI.
AB  - The anterior aspect of the knee is host to an array of normal variants and
      potential pathology. These normal anatomic variants are often encountered and may
      mimic pathologies, leading to unnecessary work-up and treatments. On the other
      hand, there are several subtle abnormalities that may be easily overlooked or
      mistaken for variants or other injuries or diseases. Recognition of these
      diagnostic challenges is essential for radiologists to make an accurate
      diagnosis. This article reviews normal anatomical variants of ligaments, tendons,
      bones, and other important structures of the anterior knee, focusing on magnetic
      resonance imaging features. Commonly encountered injuries and abnormalities of
      the anterior knee and their diagnostic pitfalls are also discussed, highlighting
      findings on magnetic resonance imaging.

PMID- 29574493
TI  - Immigrant Respiratory Health: a Diverse Perspective in Environmental Influences
      on Respiratory Health.
AB  - PURPOSE OF REVIEW: The aim of this review is to examine the prevalence of and
      impact of environmental exposures in the workplace and home on immigrant
      respiratory health in the USA. RECENT FINDINGS: Few studies report levels of
      workplace and home environmental exposures for immigrant children and adults, and
      documenting these findings is an important first step to addressing their
      respiratory health concerns. Rates of respiratory disease are lowest upon first
      arrival and increase with duration of residency in the USA. Community Health
      Workers may be an efficacious intervention to reducing exposures and improving
      lung health among immigrant populations. Immigrant children and adults have a
      high risk of occupational and home environmental exposures that can negatively
      affect their respiratory health. While limited studies exist, more documentation
      of these exposures and their impact on immigrant person's respiratory health are
      needed to begin to tackle these disparities.

PMID- 29574494
TI  - Motion Correction and Its Impact on Absolute Myocardial Blood Flow Measures with
      PET.
AB  - PURPOSE OF REVIEW: Motion artifacts, due to cardiac and respiratory cycles,
      myocardial cardiac creep, or gross patient movements, have been extensively
      investigated in the context of relative myocardial perfusion imaging with SPECT
      and PET. These movements have been identified as a major source of errors in
      image quantification and diagnosis. Recently, as dynamic PET quantification for
      myocardial blood flow assessment has entered clinical practice, similar questions
      have arisen on the impact of motion on final blood flow values. RECENT FINDINGS:
      While preliminary investigations have underlined the potential impact of these
      motions on MBF quantification, their correction on dynamic acquisition remains
      challenging and limited to research studies. Gross patient's body movements occur
      in a consistent number of cases, particularly during stress acquisition,
      typically involving a limited number of image frames. If undetected, these
      movements can lead to great differences in flow values and consequently
      misdiagnosis. Quality control routines can be applied to automatically inspect
      the shape of time activity curves and to help identify motion artifacts. Cyclic
      cardiac and respiratory motion may have a considerable impact on final flow
      values. Correction of gross body motion represents a priority in the context of
      optimizing absolute flow clinical routine utilization and protocol
      standardization.

PMID- 29574495
TI  - Divergence of Funneliformis mosseae populations over 20 years of laboratory
      cultivation, as revealed by vegetative incompatibility and molecular analysis.
AB  - Arbuscular mycorrhizal fungi (AMF) are widespread, important plant symbionts.
      They absorb and translocate mineral nutrients from the soil to host plants
      through an extensive extraradical mycelium, consisting of indefinitely large
      networks of nonseptate, multinucleated hyphae which may be interconnected by
      hyphal fusions (anastomoses). This work investigated whether different lineages
      of the same isolate may lose the ability to establish successful anastomoses,
      becoming vegetatively incompatible, when grown separately. The occurrence of
      hyphal incompatibility among five lineages of Funneliformis mosseae, originated
      from the same ancestor isolate and grown in vivo for more than 20 years in
      different European locations, was assessed by systematic detection of anastomosis
      frequency and cytological studies. Anastomosis frequencies ranged from 60 to 80%
      within the same lineage and from 17 to 44% among different lineages. The
      consistent detection of protoplasm continuity and nuclei in perfect fusions
      showed active protoplasm flow both within and between lineages. In pairings
      between different lineages, post-fusion incompatible reactions occurred in 6-48%
      of hyphal contacts and pre-fusion incompatibility in 2-17%. Molecular
      fingerprinting profiles showed genetic divergence among lineages, with overall
      Jaccard similarity indices ranging from 0.85 to 0.95. Here, phenotypic divergence
      among the five F. mosseae lineages was demonstrated by the reduction of their
      ability to form anastomosis and the detection of high levels of vegetative
      incompatibility. Our data suggest that potential genetic divergence may occur in
      AMF over only 20 years and represent the basis for detailed studies on the
      relationship between genes regulating anastomosis formation and hyphal
      compatibility in AMF.

PMID- 29574496
TI  - Impact of soil pedogenesis on the diversity and composition of fungal communities
      across the California soil chronosequence of Mendocino.
AB  - Understanding how soil pedogenesis affects microbial communities and their in
      situ activities according to ecosystem functioning is a central issue in soil
      microbial ecology, as soils represent essential nutrient reservoirs and habitats
      for the biosphere. To address this question, soil chronosequences developed from
      a single, shared mineralogical parent material and having the same climate
      conditions are particularly useful, as they isolate the factor of time from other
      factors controlling the character of soils. In our study, we considered a natural
      succession of uplifted marine terraces in Mendocino, CA, ranging from highly
      fertile in the younger terrace (about 100,000 years old) to infertile in the
      older terraces (about 300,000 years old). Using ITS amplicon pyrosequencing, we
      analysed and compared the diversity and composition of the soil fungal
      communities across the first terraces (T1 to T3), with a specific focus in the
      forested terraces (T2 and T3) on soil samples collected below trees of the same
      species (Pinus muricata) and of the same age. While diversity and richness
      indices were highest in the grassland (youngest) terrace (T1), they were higher
      in the older forested terrace (T3) compared to the younger forested terrace (T2).
      Interestingly, the most abundant ectomycorrhizal (ECM) taxa that we found within
      these fungal communities showed high homology with ITS Sanger sequences obtained
      previously directly from ECM root tips from trees in the same study site,
      revealing a relative conservation of ECM diversity over time. Altogether, our
      results provide new information about the diversity and composition of the fungal
      communities as well as on the dominant ECM species in the soil chronosequence of
      Mendocino in relation to soil age and ecosystem development.

PMID- 29574497
TI  - Defining the contribution of chronic kidney disease to all-cause mortality in
      patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events
      (RIACE) Italian Multicenter Study.
AB  - AIMS: To define the contribution of chronic kidney disease (CKD) to excess
      mortality in patients with type 2 diabetes and identify the baseline variables
      associated with all-cause death in those with and without CKD using the RECursive
      Partitioning and Amalgamation (RECPAM) method. METHODS: This observational,
      longitudinal, cohort study enrolled 15,773 consecutive non-dialytic patients with
      type 2 diabetes in 19 Diabetes Clinics throughout Italy in 2006-2008. Based on
      the presence of albuminuria >= 30 mg day-1 and/or estimated glomerular filtration
      rate (eGFR) < 60 mL min-1.1.73 m-2 at baseline, patients were classified as
      having or not CKD. Vital status was verified on October 31, 2015 for 99.26% of
      patients. RESULTS: Mortality increased with increasing albuminuria and eGFR
      category. Excess risk versus the general population was maximal in patients aged
      < 55 years in the worse albuminuria or eGFR category. Conversely, in subjects
      aged >= 75 years with albuminuria < 10 mg day-1 or eGFR >= 75 mL min-1.1.73 m-2,
      excess mortality was no longer detectable. At RECPAM analysis, the main
      correlates of death in the whole cohort were albuminuria > 44 mg day-1, prevalent
      CVD, and eGFR < ~ 75 mL min-1.1.73 m-2; gender, prevalent CVD, and higher
      albuminuria in the normoalbuminuric range, in patients without CKD; and CVD, eGFR
      ~ < 50 mL min-1.1.73 m-2, and albuminuria > 53 mg day-1, in those with CKD.
      CONCLUSIONS: CKD is a major contributor to excess mortality in type 2 diabetes,
      conferring a very high risk in younger patients and fully accounting for excess
      risk in the older ones. Higher albuminuria and lower eGFR, even in the normal
      range, identify individuals with increased mortality risk. Trial registration
      ClinicalTrials.gov (NCT00715481; https://clinicaltrials.gov/ct2/show/NCT00715481
      ).

PMID- 29574498
TI  - Pond bank access as an approach for managing toxic cyanobacteria in beef cattle
      pasture drinking water ponds.
AB  - Forty-one livestock drinking water ponds in Alabama beef cattle pastures during
      were surveyed during the late summer to generally understand water quality
      patterns in these important water resources. Since livestock drinking water ponds
      are prone to excess nutrients that typically lead to eutrophication, which can
      promote blooms of toxigenic phytoplankton such as cyanobacteria, we also assessed
      the threat of exposure to the hepatotoxin, microcystin. Eighty percent of the
      ponds studied contained measurable microcystin, while three of these ponds had
      concentrations above human drinking water thresholds set by the US Environmental
      Protection Agency (i.e., 0.3 MUg/L). Water quality patterns in the livestock
      drinking water ponds contrasted sharply with patterns typically observed for
      temperate freshwater lakes and reservoirs. Namely, we found several non-linear
      relationships between phytoplankton abundance (measured as chlorophyll) and
      nutrients or total suspended solids. Livestock had direct access to all the study
      ponds. Consequently, the proportion of inorganic suspended solids (e.g.,
      sediment) increased with higher concentrations of total suspended solids, which
      underlies these patterns. Unimodal relationships were also observed between
      microcystin and phytoplankton abundance or nutrients. Euglenoids were abundant in
      the four ponds with chlorophyll concentrations > 250 MUg/L (and dominated three
      of these ponds), which could explain why ponds with high chlorophyll
      concentrations would have low microcystin concentrations. Based on observations
      made during sampling events and available water quality data, livestock-mediated
      bioturbation is causing elevated total suspended solids that lead to reduced
      phytoplankton abundance and microcystin despite high concentrations of nutrients,
      such as phosphorus and nitrogen. Thus, livestock could be used to manage algal
      blooms, including toxic secondary metabolites, in their drinking water ponds by
      allowing them to walk in the ponds to increase turbidity.

PMID- 29574499
TI  - The correlation between the quality of oral hygiene and oral HPV infection in
      adults: a prospective cross-sectional study.
AB  - OBJECTIVES: Various risk factors for oral human papillomavirus (HPV) infections
      have been described, including tobacco smoking and sexual behavior. However, less
      is known about the influence of oral health on such infections. The present study
      aimed to determine a possible association between the quality of oral hygiene and
      the presence of oral HPV. METHODS: In a prospective analysis, the approximal
      plaque index (API), the gingival bleeding index (GBI), and the lifetime number of
      extracted teeth was determined in 187 patients. Additionally, the presence of
      oral low-risk and/or high-risk HPV was investigated by brush smear testing in all
      participants. RESULTS: Seventy-four patients had an API < 20%, 84 participants
      showed an API of 20-40%, and in 29 cases, an API > 40% was recorded. Ninety-six
      patients presented a GBI < 20%, 75 had a GBI of 20-40%, and 16 showed a GBI >
      40%. One hundred four patients had experienced one to three extractions, and 36
      had lost more than three teeth. Thirty-nine participants had a positive oral HPV
      testing (27 high-risk HPV, 26 low-risk HPV, 14 low- and high-risk HPV). A higher
      API respectively GBI and a greater number of extracted teeth were significantly
      correlated with the presence of high-risk HPV. The presence of low-risk HPV was
      significantly higher in patients with API > 40% and GBI > 40% (OR 7.89). Similar
      results were found regarding the number of extracted teeth. CONCLUSION: The
      present analysis confirms a relationship between the quality of oral hygiene,
      determined by objective markers. Thus, improvement of oral health may reduce the
      incidence of oral HPV infection. CLINICAL SIGNIFICANCE: The present article
      investigates the relationship between oral hygiene and the presence of oral HPV.
      As a significant correlation between these two factors could be recorded,
      improvement of oral hygiene may reduce actively the incidence of oral HPV.
      Thereby, good oral hygiene may contribute oral cancer prevention.

PMID- 29574500
TI  - Meaningful Assessment of Robotic Surgical Style using the Wisdom of Crowds.
AB  - OBJECTIVE: Quantitative assessment of surgical skills is an important aspect of
      surgical training; however, the proposed metrics are sometimes difficult to
      interpret and may not capture the stylistic characteristics that define
      expertise. This study proposes a methodology for evaluating the surgical skill,
      based on metrics associated with stylistic adjectives, and evaluates the ability
      of this method to differentiate expertise levels. METHODS: We recruited subjects
      from different expertise levels to perform training tasks on a surgical
      simulator. A lexicon of contrasting adjective pairs, based on important skills
      for robotic surgery, inspired by the global evaluative assessment of robotic
      skills tool, was developed. To validate the use of stylistic adjectives for
      surgical skill assessment, posture videos of the subjects performing the task, as
      well as videos of the task were rated by crowd-workers. Metrics associated with
      each adjective were found using kinematic and physiological measurements through
      correlation with the crowd-sourced adjective assignment ratings. To evaluate the
      chosen metrics' ability in distinguishing expertise levels, two classifiers were
      trained and tested using these metrics. RESULTS: Crowd-assignment ratings for all
      adjectives were significantly correlated with expertise levels. The results
      indicate that naive Bayes classifier performs the best, with an accuracy of
      [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see
      text] when classifying into four, three, and two levels of expertise,
      respectively. CONCLUSION: The proposed method is effective at mapping
      understandable adjectives of expertise to the stylistic movements and
      physiological response of trainees.

PMID- 29574501
TI  - Analytical Expressions for the Mixed-Order Kinetics Parameters of TL Glow Peaks
      Based on the two Heating Rates Method.
AB  - The two heating rates method (originally developed for first-order glow peaks)
      was used for the first time to evaluate the activation energy (E) from glow peaks
      obeying mixed-order (MO) kinetics. The derived expression for E has an
      insignificant additional term (on the scale of a few meV) when compared with the
      first-order case. Hence, the original expression for E using the two heating
      rates method can be used with excellent accuracy in the case of MO glow peaks. In
      addition, we derived a simple analytical expression for the MO parameter. The
      present procedure has the advantage that the MO parameter can now be evaluated
      using analytical expression instead of using the graphical representation between
      the geometrical factor and the MO parameter as given by the existing peak shape
      methods. The applicability of the derived expressions for real samples was
      demonstrated for the glow curve of Li2B4O7:Mn single crystal. The obtained
      parameters compare very well with those obtained by glow curve fitting and with
      the available published data.

PMID- 29574502
TI  - Synthesis and antimicrobial evaluation of novel 1,2,4-triazole thioether
      derivatives bearing a quinazoline moiety.
AB  - A series of structurally novel 3-thioether-1-(quinazolin-4-yl)-1H-1,2,4-triazol-5
      amine derivatives (7a-7r) were designed and synthesized based on a pharmacophore
      hybrid approach, and screened for their antibacterial and antifungal activities
      in vitro. All the target compounds were fully characterized through [Formula: see
      text]H NMR, [Formula: see text]C NMR and HRMS spectra. Among them, the structure
      of compound 7b was further confirmed via single-crystal X-ray diffraction
      analysis. The obtained results indicated that several target compounds
      demonstrated notable inhibition activities against tested phytopathogenic
      bacteria, using a turbidimetric method. For example, compounds 7d, 7g and 7i
      exhibited EC[Formula: see text] (half-maximal effective concentration) values of
      46.9, 47.8 and 43.2 ug/mL, respectively, against the bacterium Xanthomonas
      axonopodis pv. citri (Xac), which were more potent than commercial
      agrobactericide Bismerthiazol (56.9 ug/mL). Moreover, EC[Formula: see text]
      values of compounds 7a and 7h were found to be 81.6 and 93.1 ug/mL, respectively,
      against the bacterium Ralstonia solanacearum (Rs), being over twofold more active
      than commercial agrobactericide Thiodiazole-copper (189.6 ug/mL). Finally, some
      compounds displayed a certain degree of inhibition activity against tested
      phytopathogenic fungi at 50 ug/mL.

PMID- 29574503
TI  - Evidence, Emotion and Eminence: A Qualitative and Evaluative Analysis of Doctors'
      Skills in Macroallocation.
AB  - In this analysis of the ethical dimensions of doctors' participation in
      macroallocation we set out to understand the skills they use, how they are
      acquired, and how they influence performance of the role. Using the principles of
      grounded moral analysis, we conducted a semi-structured interview study with
      Australian doctors engaged in macroallocation. We found that they performed
      expertise as argument, bringing together phronetic and rhetorical skills founded
      on communication, strategic thinking, finance, and health data. They had made
      significant, purposeful efforts to gain skills for the role. Our findings
      challenge common assumptions about doctors' preferences in argumentation, and
      reveal an unexpected commitment to practical reason. Using the ethics of Paul
      Ricoeur in our analysis enabled us to identify the moral meaning of doctors'
      skills and learning. We concluded that Ricoeur's ethics offers an empirically
      grounded matrix for ethical analysis of the doctor's role in macroallocation that
      may help to establish norms for procedure.

PMID- 29574505
TI  - Hymenobacter agri sp. nov., a novel bacterium isolated from soil.
AB  - A bacterial isolate was recovered from a soil sample collected in Jeollabuk-do
      Province, South Korea, and subjected to polyphasic taxonomic assessment. Cells of
      the isolate, designated strain S1-2-1-2-1T, were observed to be rod-shaped, pink
      in color, and Gram-stain negative. The strain was able to grow at temperature
      range from 10 to 30  degrees C, with an optimum of 25  degrees C, and growth
      occurred at pH 6-8. Comparative 16S rRNA gene sequence analysis showed that
      strain S1-2-1-2-1T belongs to the genus Hymenobacter, with closely related type
      strains being Hymenobacter daeguensis 16F3Y-2T (95.8% similarity), Hymenobacter
      rubidus DG7BT (95.8%), Hymenobacter soli PBT (95.7%), Hymenobacter terrenus
      MIMtkLc17T (95.6%), Hymenobacter terrae DG7AT (95.3%), and Hymenobacter
      saemangeumensis GSR0100T (95.2%). The genomic DNA G+C content of strain S1-2-1-2
      1T was 63.0 mol%. The main polar lipid of this strain was
      phosphatidylethanolamine, the predominant respiratory quinone was menaquinone-7,
      and the major fatty acids were C15:0 iso (27.3%), summed feature 3 (C16:1
      omega7c/C16:1 omega6c) (16.5%), C15:0 anteiso (15.3%), and C16:0 (14.7%),
      supporting the affiliation of this strain with the genus Hymenobacter. The
      results of this polyphasic analysis allowed for the genotypic and phenotypic
      differentiation of strain S1-2-1-2-1T from recognized Hymenobacter species. On
      the basis of its phenotypic properties, genotypic distinctiveness, and
      chemotaxonomic features, strain S1-2-1-2-1T is considered to represent a novel
      species of the genus Hymenobacter, for which the name Hymenobacter agri sp. nov.
      is proposed. The type strain is S1-2-1-2-1T (=KCTC 52739T = JCM 32194T).

PMID- 29574504
TI  - Ventilatory and cerebrovascular regulation and integration at high-altitude.
AB  - Ascent to high-altitude elicits compensatory physiological adaptations in order
      to improve oxygenation throughout the body. The brain is particularly vulnerable
      to the hypoxemia of terrestrial altitude exposure. Herein we review the
      ventilatory and cerebrovascular changes at altitude and how they are both
      implicated in the maintenance of oxygen delivery to the brain. Further, the
      interdependence of ventilation and cerebral blood flow at altitude is discussed.
      Following the acute hypoxic ventilatory response, acclimatization leads to
      progressive increases in ventilation, and a partial mitigation of hypoxemia.
      Simultaneously, cerebral blood flow increases during initial exposure to altitude
      when hypoxemia is the greatest. Following ventilatory acclimatization to
      altitude, and an increase in hemoglobin concentration-which both underscore
      improvements in arterial oxygen content over time at altitude-cerebral blood flow
      progressively decreases back to sea-level values. The complimentary nature of
      these responses (ventilatory, hematological and cerebral) lead to a tightly
      maintained cerebral oxygen delivery while at altitude. Despite this general
      maintenance of global cerebral oxygen delivery, the manner in which this occurs
      reflects integration of these physiological responses. Indeed, ventilation
      directly influences cerebral blood flow by determining the prevailing blood gas
      and acid/base stimuli at altitude, but cerebral blood flow may also influence
      ventilation by altering central chemoreceptor stimulation via central CO2
      washout. The causes and consequences of the integration of ventilatory and
      cerebral blood flow regulation at high altitude are outlined.

PMID- 29574506
TI  - Time from colorectal cancer diagnosis to laparoscopic curative surgery-is there a
      safe window for prehabilitation?
AB  - BACKGROUND: There is a growing interest in the adoption of formal prehabilitation
      programmes prior to elective surgery but regulatory targets mandate prompt
      treatment following cancer diagnosis. We aimed to investigate if time from
      diagnosis to surgery is linked to short- and long-term outcomes. METHODS: An
      exploratory analysis was performed utilising a dedicated, prospectively populated
      database. Inclusion criteria were biopsy-proven colorectal adenocarcinoma
      undergoing elective laparoscopic surgery with curative intent. Demographics, date
      of diagnosis and surgery was captured with patients dichotomised using 4-, 8- and
      12-week time points. All patients were followed in a standardised pathway for 5
      years. Overall survival was assessed with the Kaplan-Meier log-rank method.
      RESULTS: Six hundred sixty-eight consecutive patients met inclusion criteria.
      Mean time from diagnosis to surgery was 53 days (95% CI 48.3-57.8). Identified
      risk factors for longer time to surgery were males (OR 1.92 [1.2-3.1], p =
      0.008), age <= 65 (OR 1.9 [1.2-3], p = 0.01), higher ASA scores (p = 0.01) stoma
      formation (OR 6.9 [4.1-11], p < 0.001) and neoadjuvant treatment (OR 5.06 [3.1
      8.3], p < 0.001). There was no association between time to surgery and BMI (p =
      0.36), conversion (16.3%, p = 0.5), length of stay (p = 0.33) and readmission or
      reoperation (p = 0.3). No differences in five-year survival were seen in those
      operated within 4, 8 and 12 weeks (p = 0.397, p = 0.962 and p = 0.611,
      respectively). Multivariate analysis showed time from diagnosis to surgery was
      not associated with five-year overall survival (HR 0.99, p = 0.52). CONCLUSION:
      Time from colorectal cancer diagnosis to curative laparoscopic surgery did not
      impact on overall survival. This finding may allow preoperative pathway
      alteration without compromising safety.

PMID- 29574508
TI  - Scopoletin intervention in pancreatic endoplasmic reticulum stress induced by
      lipotoxicity.
AB  - Endoplasmic reticulum (ER), a dynamic organelle, plays an essential role in
      organizing the signaling pathways involved in cellular adaptation, resilience,
      and survival. Impairment in the functions of ER occurs in a variety of nutritive
      disorders including obesity and type 2 diabetes. Here, we hypothesize that
      (scopoletin) SPL, a coumarin, has the potential to alleviate ER stress induced in
      vitro and in vivo models by lipotoxicity. To test this hypothesis, the ability of
      SPL to restore the levels of proteins of ER stress was analyzed. Rat insulinoma
      5f (RIN5f) cells and Sprague Dawley rats were the models used for this study.
      Groups of control and high-fat, high-fructose diet (HFFD)-fed rats were treated
      with either SPL or 4-phenylbutyric acid. Status of ER stress was enumerated by
      quantitative RT-PCR, Western blot, electron microscopic, and immunohistochemical
      studies. Proximal proteins of ER stress inositol requiring enzyme 1 (IRE1),
      protein kinase like endoplasmic reticulum kinase (PERK), and activating
      transcription factor 6 (ATF6) were reduced in the beta-cells by SPL. The
      subsequent signaling proteins X-box binding protein 1, eukaryotic initiation
      factor2alpha, activating transcription factor 4, and C/EBP homologous protein
      were also suppressed in their expression levels when treated with SPL. IRE1, PERK
      signaling leads to c-Jun-N-terminal kinases phosphorylation, a kinase that
      interrupts insulin signaling, which was also reverted upon scopoletin treatment.
      Finally, we confirm that SPL has the ability to suppress the stress proteins and
      limit pancreatic ER stress which might help in delaying the progression of
      insulin resistance.

PMID- 29574507
TI  - New steps for treating alcohol use disorder.
AB  - Alcohol use disorder is a complex syndrome with multiple treatment points
      including drug-induced pathology, withdrawal management, behavioral/cognitive
      strategies, and relapse prevention. These different components may be complicated
      by genotype and phenotype. A huge milestone for the treatment of alcohol use
      disorder across several countries in the last 10 years was the introduction of
      practice guidelines integrating clinical expertise and research evidence. These
      provide a summary of interventions that have been shown to be effective following
      rigorous and replicated clinical trials. Inspection of these guidelines reveals
      good consistency, but little evidence of progress in treatment approaches for
      alcohol use disorder over the past decade. In this mini-review, we discuss
      emerging treatments for alcohol use disorder that may supplement or improve the
      evidence-based treatments that are currently recommended. New medications, the
      emergence of digital technology, and other novel approaches such as transcranial
      magnetic stimulation are all discussed with reference to treatments already in
      practice. We also consider how individual differences in genotype and phenotype
      may affect outcomes. Together with improvements in technology, this knowledge
      offers a powerful tool for designing personalized approaches to treatment, and
      hence improving prognosis for rehabilitation programs.

PMID- 29574509
TI  - Linkage disequilibrium and functional analysis of PRE1 insertion together with
      SNPs in the promoter region of IGFBP7 gene in different pig breeds.
AB  - Polymorphisms in regions upstream of transcription initiation site may modify the
      transcriptional activity of target genes by changing promoter activity. This
      study aims to determine whether or not polymorphisms at porcine IGFBP7 promoter
      region affect gene expression. In this study, eight SNPs and one PRE1 insertion
      in this region were first confirmed. The PRE1 insertion was widespread in 20
      Chinese indigenous breeds, but was not observed in three commercial breeds. A
      perfect linkage disequilibrium, consisting of six of those SNPs and a PRE1, was
      observed with two haplotypes (h1 and h2) in five pig breeds. The h1 haplotype had
      an overwhelming superiority distribution in Large White, Landrace, and Bama mini
      pig; in turn, the h2 only existed in the PRE1 presence breeds. As the haplotypes
      and PRE1 were located at gene promoter regions, we further investigated the
      transfection of plasmids with three different fragments of IGFBP-7 promoter
      region (H1, H2, RF). The CMV promoter of the pEGFP-N1 was substituted by these
      three different fragments, respectively. Different transcriptional and
      translational activities of EGFP in PK-15 cells were observed in these three
      recombinant plasmids by quantitative real-time PCR and flow cytometric analysis.
      The results indicated that H1 had the higher transcriptional and translational
      activities of EGFP as compared to the H2 (P < 0.05, P < 0.05). As compared to the
      RF group, EGFP mRNA expression level was significantly higher in H1 groups (P <
      0.05). The IGFBP-7 promoter polymorphisms detected in this study may be important
      functional variants and potential genetic markers for pig population genetic
      study.

PMID- 29574510
TI  - MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived
      Mesenchymal Stem Cells to Cardiomyocytes.
AB  - Since the adult mammalian heart has limited regenerative capacity, cardiac
      trauma, disease, and aging cause permanent loss of contractile tissue. This has
      fueled the development of stem cell-based strategies to provide the damaged heart
      with new cardiomyocytes. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are
      capable of self-renewal and differentiation into cardiomyocytes, albeit
      inefficiently. MicroRNAs (miRNAs, miRs) are non-coding RNAs that have the
      potential to control stem cell fate decisions and are employed in cardiac
      regeneration and repair. In this study, we tested the hypothesis that
      overexpression of miR-499a induces cardiomyogenic differentiation in BM-MSCs.
      Human BM-MSCs (hBM-MSCs) were transduced with lentiviral vectors encoding miR
      499a-3p or miR-499a-5p and analyzed by immunostaining and western blotting
      methods 14 days post-transduction. MiR-499a-5p-transduced cells adopted a
      polygonal/rod-shaped (myocyte-like) phenotype and showed an increase in the
      expression of the cardiomyocyte markers alpha-actinin and cTnI, as cardiogenic
      differentiation markers. These results indicate that miR-499a-5p overexpression
      promotes the cardiomyogenic differentiation of hBM-MSCs and may thereby increase
      their therapeutic efficiency in cardiac regeneration.

PMID- 29574511
TI  - Small Ubiquitin-Like Modifier Protein 3 Enhances the Solubilization of Human Bone
      Morphogenetic Protein 2 in E. coli.
AB  - Small ubiquitin-like modifier (SUMO) fusion technology is widely used in the
      production of heterologous proteins from prokaryotic system to aid in protein
      solubilization and refolding. Due to an extensive clinical application of human
      bone morphogenetic protein 2 (hBMP2) in bone augmentation, total RNA was isolated
      from human gingival tissue and mature gene was amplified through RT-PCR, cloned
      (pET21a), sequence analyzed, and submitted to GenBank (Accession no. KF250425).
      To obtain soluble expression, SUMO3 was tagged at the N-terminus of hBMP2 gene
      (pET21a/SUMO3-hBMP2), transferred in BL21 codon+, and ~ 40% soluble expression
      was obtained on induction with IPTG. The dimerized hBMP2 was confirmed with
      Western blot, native PAGE analysis, and purified by fast protein liquid
      chromatography with 0.5 M NaCl elution. The cleavage of SUMO3 tag from hBMP2
      converted it to an insoluble form. Computational 3D structural analysis of the
      SUMO3-hBMP2 was performed and optimized by molecular dynamic simulation. Protein
      protein interaction of SUMO3-hBMP2 with BMP2 receptor was carried out using
      HADDOCK and inferred stable interaction. The alkaline phosphatase assay of SUMO3
      hBMP2 on C2C12 cells showed maximum 200-ng/ml dose-dependent activity. We
      conclude that SUMO3-tagged hBMP2 is more suited for generation of soluble form of
      the protein and addition of SUMO3 tag does not affect the functional activity of
      hBMP2.

PMID- 29574512
TI  - Minimally invasive plate osteosynthesis in humerus nonunion after intramedullary
      nailing.
AB  - INTRODUCTION: The purpose of this study was to evaluate the results achieved
      after the use of lateral minimally invasive plate osteosynthesis (MIPO) in
      oligotrophic humerus nonunions resulting from failed intramedullary nailing (IM).
      METHOD: We evaluated nine patients with humerus nonunion after failed locked
      intramedullary nailing, all treated using 3.5-mm locked compression plates (LCP)
      placed through lateral minimally invasive approaches, between 2010 and 2016.
      Patient's age averaged 39.7 years. All nonunions were diaphyseal and
      oligotrophic. All nonunions had previous surgical treatment with static locked
      nails (seven antegrade and two retrograde). The IM nails were all well inserted
      in the humerus (none of them protruded or had rotator cuff lesions associated).
      Pre-operative Disabilities of the Arm, Shoulder and Hand (DASH) score averaged
      25.5 points. Pre-operative Constant's score averaged 80.2. Pre-operative visual
      analog scale of pain averaged 2.4 points. RESULTS: Follow-up averaged 17.7
      months. Time between initial surgery and revision procedure averaged 11.7 months.
      Union was achieved in all cases, after an average of 4.8 months. DASH score at
      last follow-up averaged 5.1 points, and final Constant's score averaged 93.7
      points. The analog scale of pain averaged 0.7 points. Time from definitive
      surgery to work return averaged 3.9 months. Long 3.5-mm LCPs were used (plate
      length averaged 16.9 screw holes). In two cases, a third 4-cm incision at the
      nonunion site was performed and cancellous autologous iliac crest bone graft was
      associated. CONCLUSION: In our series of nine patients, we achieved union and
      good objective and subjective results, with high patient satisfaction, using a
      lateral MIPO technique and placing long 3.5-mm LCPs in selected oligotrophic
      humerus nonunions after failed IM nailing.

PMID- 29574513
TI  - Insights into phytase-containing transgenic Lemna minor (L.) as a novel feed
      additive.
AB  - This study assessed the effect of supplementation of novel transgenic phytase on
      growth performance and bone mineralization in Korean native broiler chickens. The
      experiment was designed using four dietary groups: those with a diet supplemented
      with (A) recombinant phytase, (B) transgenic phytase from the plant Lemna minor,
      (C) or wild-type L. minor as well as (D) a control group that was supplemented
      with commercially available feed. Three hundred 1-day-old Korean native broiler
      chicks were used and divided into these four dietary treatment groups having
      three replicates of 25 birds each (n = 75). The results showed increases in
      growth performance and bone mineralization in Groups B and C; compared with
      Groups A and D. Hematological analyses revealed notable contrasts in erythrocyte
      sedimentation rate, red blood cell count, and hemoglobin levels among the
      experimental groups, whereas no impacts of dietary treatment were observed on
      total eosinophil, lymphocyte, heterophil, monocyte, and basophil levels. The
      relative expression profiling of candidate genes showed that the genes involved
      in growth response, meat quality, and P-Ca metabolism were significantly highly
      expressed in the phytase-supplemented groups. Hence, it is suggested that dietary
      supplementation with transgenic phytase plant L. minor for enhancing growth
      performance is a promising new approach in the broiler feed industry. To the best
      of our knowledge, we report here the most comprehensive analysis using a broiler
      model that provides a workable platform for further research on the cost
      effective production of feed with different compositions that might be beneficial
      in the livestock feed industry.

PMID- 29574514
TI  - Longitudinal study for anthelmintic efficacy against intestinal helminths in
      naturally exposed Lithuanian village dogs: critical analysis of feasibility and
      limitations.
AB  - The efficacy of anthelmintic treatment at 1, 3, and 6 month intervals was
      evaluated in a prospective controlled field study with naturally exposed
      Lithuanian village dogs by monthly coproscopy during 1 year. A placebo-treated
      control group (C) (n = 202) and groups treated with two broad-spectrum
      anthelmintics, febantel/pyrantel-embonate/praziquantel (Drontal(r) Plus, Bayer)
      (D1, D3, D6; n = 113-117) and emodepside/praziquantel (Profender(r), Bayer) (P1,
      P3, P6; n = 114-119), were included. At the beginning of the study, eggs of
      Toxocara canis (4.02%) and T. cati (0.44%) identified morphometrically and/or
      molecularly and eggs of taeniid- (0.78%) and Capillaria-like eggs (5.03%) were
      present in the feces without significant differences in prevalence between
      groups. Significant decreases in excretion of T. canis eggs was found 1 month
      after the treatment with Drontal(r) Plus in February (D1) and with Profender(r)
      in October (P1), November (P1), December (P3), February (P1), and March (P1, P3),
      as compared to controls in the same months. The incidence of egg excretion per
      dog at least once a year was significantly lower in group P1 for T. canis (4.24%;
      p < 0.01) and in groups D1, P1 for taeniid eggs (0%; p < 0.01 and p < 0.001),
      when compared to controls (16.96 and 6.70%, respectively). A critical analyses of
      factors possibly responsible for intestinal passage of canine helminth eggs
      revealed that chained dogs excreted T. canis eggs more frequently 1 month after
      treatment compared to dogs in pens, particularly from November to March (p =
      0.01). The incidence of single detection of T. cati eggs was significantly
      increased in chained dogs (12.46%) as compared to fenced dogs (1.08%; p =
      0.0001).

PMID- 29574515
TI  - A regional algorithm to model mesozooplankton biomass along the southwestern Bay
      of Bengal.
AB  - A three-dimensional regression analysis attempted to model mesozooplankton (MSP)
      biomass using sea surface temperature (SST) and chlorophyll-a (Chl-a). The study
      was carried out from January 2014 to July 2015 in the southwestern Bay of Bengal
      (BoB) and sampling was carried out on board Sagar Manjusha and Sagar Purvi. SST
      ranged from 26.2 to 33.1  degrees C while Chl-a varied from 0.04 to 6.09 MUg L-1.
      During the course of the study period, there was a weak correlation (r = 0.32)
      between SST and Chl-a statistically. MSP biomass varied from 0.42 to 9.63 mg C m
      3 and inversely related with SST. Two kinds of approaches were adopted to develop
      the model by grouping seasonal datasets (four seasonal algorithms) and comprising
      all datasets (one annual algorithm). Among the four functions used (linear,
      paraboloid, the Lorentzian and the Gaussian functions), paraboloid model was best
      suited. The best seasonal and annual algorithms were applied in the synchronous
      MODIS-derived SST and Chl-a data to estimate the MSP biomass in the southwestern
      BoB. The modelled MSP biomass was validated with field MSP biomass and the result
      was statistically significant, showing maximum regression coefficient for the
      seasonal algorithms (R2 = 0.60; p = 0.627; alpha = 0.05), than the annual
      algorithm (R2 = 0.52; p = 0.015, alpha = 0.05).

PMID- 29574517
TI  - Impact of switching oral bisphosphonates to denosumab or daily teriparatide on
      the progression of radiographic joint destruction in patients with biologic-naive
      rheumatoid arthritis.
AB  - : In biologic-naive female RA patients, switching oral BPs to DMAb significantly
      reduced radiographic joint destruction compared to continuing oral BPs or
      switching to TPTD at 12 months, which were significantly associated with a
      decrease of a bone resorption marker at 6 months. INTRODUCTION: The aim of this
      study was to clarify the effects of switching oral bisphosphonates (BPs) to
      denosumab (DMAb) or daily teriparatide (TPTD) on the progression of radiographic
      joint destruction in patients with biologic-naive rheumatoid arthritis (RA).
      METHODS: A retrospective, case-controlled study involving 90 female RA patients
      (mean age 68.2 years, 96.7% postmenopausal, disease activity score assessing 28
      joints with CRP (DAS28-CRP) 2.4, methotrexate treatment 81.1%, prednisolone
      treatment 68.9%, and prior BP treatment 44.8 months), who were allocated
      depending on each patient's and physician's wishes, to (1) the BP-continue group
      (n = 30), (2) the switch-to-DMAb group (n = 30), or (3) the switch-to-TPTD group
      (n = 30), was conducted. Patients were retrospectively selected to minimize the
      difference of possible clinical backgrounds that may affect the joint destruction
      of RA. The primary endpoint was to clarify the change of the modified total Sharp
      score (mTSS) from baseline to 12 months. RESULTS: After 12 months, the mean
      changes of the modified Sharp erosion score were significantly lower in the
      switch-to-DMAb group (0.2 +/- 0.1; mean +/- standard error) than in the switch-to
      TPTD group (1.3 +/- 0.5; P < 0.05), and mTSS was significantly lower in the
      switch-to-DMAb group (0.3 +/- 0.2) than in the BP-continue group (1.0 +/- 0.3; P
      < 0.05) and the switch-to-TPTD group (1.7 +/- 0.6; P < 0.05). The logistic
      regression analysis showed that mTSS changes were significantly associated with
      the percent changes of TRACP-5b at 6 months (beta = 0.30, 95% CI = 0.002-0.016; P
      < 0.01). CONCLUSIONS: Changes of systemic bone turnover induced by switching BPs
      to DMAb or TPTD may affect not only systemic bone mass, but also local joint
      destruction, and its clinical relevance should be considered comprehensively.

PMID- 29574516
TI  - Risk of fragility fracture among patients with late-onset psoriasis: a UK
      population-based study.
AB  - : This study aimed to examine fracture risk in patients with late-onset
      psoriasis. A cohort study was conducted using primary care records from the
      Clinical Practice Research Datalink. Psoriasis patients had a 10% increased risk
      of fracture compared to matched controls (hazard ratio (HR) = 1.10; 95%
      confidence interval (CI) 1.04, 1.16). INTRODUCTION: This study aimed to examine
      fracture risk in patients with late-onset psoriasis and investigate the effect of
      methotrexate on fracture risk. METHODS: A cohort study was conducted using
      primary care records from the UK-based Clinical Practice Research Datalink.
      Individuals aged 40 years and over, with incident (new onset) diagnoses of
      psoriasis, were identified from 1990 to 2004 and followed up until 2015. For each
      exposed individual, up to four age-, gender-, and practice-matched controls were
      randomly selected. Incidence rates of fragility fracture (hip, vertebral, spine,
      radius or unspecified site) per 10,000 person-years were calculated and hazard
      rates were compared to the unexposed using Cox regression models. The risk of
      fracture was also estimated, within the exposed group for patients receiving/not
      receiving methotrexate. RESULTS: Twenty-four thousand two hundred nineteen
      patients with psoriasis and 94,820 controls were identified. The absolute rate of
      fracture in psoriasis patients was 58 per 10,000 person-years (95% CI 55, 61) and
      53 per 10,000 person-years in the matched controls (CI 52, 54). Psoriasis
      patients had a 10% increased risk of fracture compared to their matched controls
      (HR = 1.10; 95% CI 1.04, 1.16). Methotrexate use was not associated with
      increased risk (HR = 0.91; 95% CI 0.72, 1.15). CONCLUSIONS: Identifying
      additional clinical factors associated with increased fracture risk is important
      in improving fracture risk stratification. Further work is needed to determine
      the relationship between age of onset of psoriasis and fracture risk, explore
      causative explanations, and identify if existing fracture risk stratification
      tools underestimate fracture risk in patients with psoriasis.

PMID- 29574518
TI  - Effects of once-monthly minodronate versus risedronate in osteoporosis patients
      with rheumatoid arthritis: a 12-month randomized head-to-head comparison.
AB  - : A head-to-head comparison of once-monthly oral bisphosphonates minodronate
      (MIN) and risedronate (RIS) in patients with rheumatoid arthritis (RA)
      demonstrated that MIN has the same effect as RIS on increase in bone mineral
      density (BMD) and a stronger effect on inhibition of bone resorption than RIS,
      suggesting that MIN is a promising treatment option for osteoporosis patients
      with RA. INTRODUCTION: To evaluate the effect of once-monthly oral MIN in
      patients with RA, a prospective, randomized, open-label, head-to-head comparison
      with once-monthly oral RIS was conducted. METHODS: A total of 83 patients with RA
      were randomly assigned to either once-monthly oral MIN 50 mg (n = 42) or once
      monthly oral RIS 75 mg (n = 41). Serial BMD and bone turnover markers were
      measured and compared between the treatment groups. RESULTS: BMD (lumbar spine,
      total hip, femoral neck) increased significantly after 12 months of treatment
      with MIN (3.8, 2.0, and 2.2%, respectively, P < 0.05) and RIS (3.6, 1.9, and
      1.9%, respectively, P < 0.05). There were no significant differences between the
      treatment groups. Percent changes of bone turnover markers from baseline to 12
      months in the MIN group were significantly greater than those in the RIS group
      (TRACP-5b: - 36.3 vs - 19.3%, P < 0.05; NTX: - 27.1 vs - 17.3%, P < 0.05; BAP: 
      30.2 vs -19.4%, P < 0.05). CONCLUSIONS: The present study of RA patients
      demonstrated that MIN has the same effect as RIS on increase in BMD and a
      stronger effect on inhibition of bone resorption than RIS. The results suggest
      that MIN is a promising treatment option for osteoporosis patients with RA.

PMID- 29574519
TI  - Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies.
AB  - : Inconsistent findings in regard to association between thiazide diuretic use
      and the risk of fracture have been reported during the past decade. This updated
      meta-analysis, which pooled data from 11 qualified prospective designed studies,
      found that thiazides have a significant protective effect on fracture risk.
      INTRODUCTION: An updated comprehensive meta-analysis examine the association
      between thiazide diuretic use and therisk of fracture is needed. METHODS: Cohort
      studies regarding thiazide diuretic exposure and the risk of fracture, published
      from inception to May 1 2017, were identified through MEDLINE, EMBASE, SCOPUS,
      and the Cochrane Database of Systematic Reviews. The literature search, study
      selection, study appraisal, and data extraction were pre-defined in the protocol
      and were independently conducted by two investigators. Due to the heterogeneity
      of the original studies, a random effects model was used to pool the confounder
      adjusted relative risk (RR). RESULTS: Eleven eligible cohort studies involving
      2,193,160 participants were included for analysis. Overall, thiazide diuretic
      users, as compared with non-users, had a significant 14% reduction in the risk of
      all fractures (relative risk [RR], 0.86; 95% confidence interval [CI], 0.80-0.93;
      p = 0.009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95%CI,
      0.80-0.93; p = 0.009). However, the effect size associated with thiazide use
      became slightly weaker when the analysis was limited to only high-quality
      original studies (quality score > 8) (RR, 0.89; 95%CI, 0.80-0.99; p = 0.005),
      studies with a larger sample size (> 10,000) (RR, 0.90; 95%CI, 0.80-1.00; p =
      0.002), and studies published after 2007 (RR, 0.92; 95%CI, 0.82-1.02; p = 0.001).
      CONCLUSION: Our findings indicate that thiazide diuretic use may convey a
      decreased risk of fracture and as such, the protective effect of this class of
      medicine should be considered when prescribing thiazide diuretics in clinical
      practice.

PMID- 29574520
TI  - Sleep duration and the risk of osteoporosis among middle-aged and elderly adults:
      a dose-response meta-analysis.
AB  - It remains unclear how many hours of sleep are associated with the lowest risk of
      osteoporosis. This meta-analysis was performed to assess the dose-response
      relationship between sleep duration and risk of osteoporosis. PubMed and Web of
      Science were searched from inception to December 3, 2017, supplemented by manual
      searches of the bibliographies of retrieved articles. Data were pooled using
      fixed- and random-effects models. Restricted cubic spline analysis with four
      knots was used to model the sleep duration and osteoporosis association. Four
      cross-sectional studies with eight records were eligible for inclusion in the
      meta-analysis. A U-shaped dose-response relationship was observed between sleep
      duration and risk of osteoporosis, with the lowest risk observed at a sleep
      duration category of 8-9 h per day. Compared with 8-h sleep duration per day, the
      pooled odds ratio for osteoporosis were 1.03 (95% CI 1.01-1.06) for each 1-h
      reduction among individuals with shorter sleep duration and 1.01 (95% CI 1.00
      1.02) for each 1-h increment among individuals with longer sleep duration. Our
      dose-response meta-analysis shows a U-shaped relationship between sleep duration
      and risk of osteoporosis, with the lowest osteoporosis risk at about 8 h per day
      of sleep duration. Both short and long sleep duration is associated with a
      significantly increased risk of osteoporosis in the middle-aged and elderly
      adults, appropriate sleep duration could help for delay or prevention of
      osteoporosis.

PMID- 29574521
TI  - Could bioelectric impedance spectroscopy (BIS) measured appendicular
      intracellular water serve as a lean mass measurement in sarcopenia definitions? A
      pilot study.
AB  - : DXA lean mass measurement for sarcopenia diagnosis is not always possible.
      Bioelectric impedance spectroscopy (BIS), a portable technology, is a potential
      alternative to DXA-measured lean mass. This pilot study explores the possibility
      and proposes an arbitrarily chosen potential cut-point for appendicular
      intracellular water corrected by height (aICW/ht2). INTRODUCTION: Sarcopenia
      definitions often include DXA lean mass measurement. However, DXA is not always
      available. We explored the potential of a less-expensive mobile method,
      bioelectric impedance spectroscopy (BIS), to assess lean mass for sarcopenia
      determination. We hypothesized that BIS-measured appendicular intracellular water
      (aICW/ht2) would correlate with DXA-measured appendicular lean mass (ALM)/ht2 and
      with functional parameters. If so, establishing an aICW/ht2 cut-point in
      sarcopenia definitions may be feasible. METHODS: Sixty-one community-dwelling
      women, mean age 79.9, had BIS and DXA lean mass, grip strength, gait speed, and
      jumping mechanography assessments. BIS aICW was calculated using limb length and
      intracellular water resistance. aICW/ht2 was compared to DXA-measured ALM/ht2 by
      linear regression. The European Working Group ALM/ht2 and an exploratory aICW/ht2
      cut-point were utilized. RESULTS: In this cohort, ALM/ht2 and aICW/ht2 were
      moderately correlated, R2 = 0.55, p < 0.0001. Lean mass was low in 7 and normal
      in 44 by BIS and DXA. Those with low aICW/ht2 had lower grip strength (p = 0.04)
      and jump power (p = 0.0002) than those with normal aICW/ht2 and ALM/ht2. Subjects
      with low ALM/ht2 had lower jump power (p = 0.0006) but were not different in gait
      speed or grip strength. CONCLUSIONS: BIS aICW is correlated with DXA-measured ALM
      directly, and when height adjusted. An aICW/ht2 cut-point of 6.5 L/m2 identified
      70% of women with low ALM/ht2. Women with low lean mass by DXA and BIS had poorer
      function measured by jump power. These pilot data support further evaluation of
      BIS measurement inclusion into sarcopenia definitions.

PMID- 29574522
TI  - Number of acinar cells at the pancreatic stump predicts pancreatic fistula after
      pancreaticoduodenectomy.
AB  - PURPOSE: To establish if the number of pancreatic acinar cells at the pancreatic
      cut end is a predictor of postoperative pancreatic fistula (POPF). METHODS: The
      number of acinar cells was assessed histologically in 121 consecutive patients
      who underwent pancreaticoduodenectomy (PD) between April, 2012 and July, 2016.
      RESULTS: POPF developed in 23 of the 121 patients. Univariate analysis revealed
      that male sex, long operating time, high volume of blood loss, soft remnant
      pancreas, large pancreatic duct, and the number of pancreatic acinar cells were
      significantly associated with POPF. Multivariate analysis revealed that male sex
      (p = 0.022) and the number of pancreatic acinar cells (p < 0.0001) were
      independently associated with POPF. In the receiver operating characteristic
      (ROC) curve analysis, the area under curve was 0.83895 when the cut off value of
      the number of pancreatic acinar cells to predict POPF was 890. Sensitivity and
      specificity of the number of pancreatic acinar cells were 82.6 and 77.6%,
      respectively. CONCLUSIONS: A large number of pancreatic acinar cells at the cut
      end of the stump is predictive of POPF after PD. Although POPF is associated with
      multiple factors and the number of acinar cells is only one of these, our study
      is the first to confirm this common intuition of surgeons, which has not been
      assessed definitively before.

PMID- 29574523
TI  - Alcohol consumption and early-onset risk of colorectal cancer in Japanese
      patients with Lynch syndrome: a cross-sectional study conducted by the Japanese
      Society for Cancer of the Colon and Rectum.
AB  - We conducted this study to establish whether drinking alcohol alters the risk of
      early-onset colorectal cancer (CRC) in Japanese patients with Lynch syndrome
      (LS). The subjects were 66 LS patients with pathogenic mutation of mismatch
      repair genes (MLH1, MSH2, and MSH6) from the nationwide Japanese retrospective
      multicenter study. Cox proportional hazards modeling was used to investigate the
      factors correlating with early-onset CRC diagnosis, using clinical data such as
      gender, tobacco use, alcohol consumption, body mass index, gene mutation (MLH1,
      MSH2 vs MSH6), and family cancer history. Alcohol was significantly correlated
      with an increased risk of early-onset CRC [HR 2.44, 95% CI 1.13-5.16 (p = 0.02)],
      but tobacco use was not [HR 0.8, 95%CI 0.38-1.62 (p = 0.53)]. These findings
      suggest that alcohol consumption is correlated with an earlier onset of CRC in
      Japanese patients with LS.

PMID- 29574524
TI  - Addressing Multimorbidity and Polypharmacy in Individuals With Atrial
      Fibrillation.
AB  - PURPOSE OF REVIEW: The objectives of this review were to (1) discuss how
      multimorbidity and polypharmacy contributes to the complexity of management among
      individuals with AF and (2) identify any interventions to manage polypharmacy in
      relation to AF. RECENT FINDINGS: Based on the four landmark clinical trials of
      novel anticoagulants, the most common comorbidities with AF are hypertension,
      heart failure, diabetes, stroke and myocardial infarction. Polypharmacy was also
      found prevalent in 76.5% of patients with AF, with a median of six drugs per
      patient. Despite the consequences of polypharmacy in AF, there is very little
      evidence-based intervention designed to manage it. Hence, there is a need for
      further research to examine interventions to manage polypharmacy in relation to
      AF. Atrial fibrillation (AF) is the most common type of cardiac arrhythmia
      requiring treatment in adults. Due to the structural and/or electrophysiological
      abnormalities that occur in AF, patients are managed through the use of
      prophylactic anticoagulant and rate and/or rhythm control medications. However,
      these medications are considered high risk and can increase the chances of
      medication misadventure. Additionally, AF rarely occurs in isolation and is known
      to coexist with multiple other medical comorbidities, i.e. multimorbidity. This
      also increases the number of medications, i.e. polypharmacy and pill burden which
      results in treatment non-compliance to prescribed therapy.

PMID- 29574525
TI  - The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance
      exercise but not protein ingestion in human skeletal muscle.
AB  - PURPOSE: Dietary protein and resistance exercise (RE) are both potent stimuli of
      the mammalian target of rapamycin complex 1 (mTORC1). Sestrins1, 2, 3 are
      multifunctional proteins that regulate mTORC1, stimulate autophagy and alleviate
      oxidative stress. Of this family, Sestrin2 is a putative leucine sensor
      implicated in mTORC1 and AMP-dependent protein kinase (AMPK) regulation. There is
      currently no data examining the responsiveness of Sestrin2 to dietary protein
      ingestion, with or without RE. METHODS: In Study 1, 16 males ingested either 10
      or 20 g of milk protein concentrate (MPC) with muscle biopsies collected pre, 90
      and 210 min post-beverage consumption. In Study 2, 20 males performed a bout of
      RE immediately followed by the consumption of 9 g of MPC or carbohydrate placebo.
      Analysis of Sestrins, AMPK and antioxidant responses was examined. RESULTS:
      Dietary protein ingestion did not result in Sestrin2 mobility shift. After RE,
      Sestrin2 phosphorylation state was significantly altered and was not further
      modified by post-exercise protein or carbohydrate ingestion. With RE, AMPK
      phosphorylation remained stable, while the mRNA expressions of several
      antioxidants were upregulated. CONCLUSIONS: Dietary protein ingestion did not
      affect the signalling by the family of Sestrins. With RE, Sestrin2 was
      hyperphosphorylated, with no further evidence of a relationship to AMPK
      signalling.

PMID- 29574526
TI  - Differential item functioning for items in Berger's HIV Stigma Scale: an analysis
      of cohorts from the Indian, Swedish, and US contexts.
AB  - PURPOSE: To examine whether items in Berger's HIV Stigma Scale function
      differently with persons of different age, gender, and cultural backgrounds.
      METHODS: Secondary data from cohorts, collected in South India (n = 250), Sweden
      (n = 193), and the US (n = 603) were reanalyzed to evaluate DIF within, between,
      and across these cohorts. All participants had answered the revised version of
      the HIV stigma scale consisting of 32 items forming the subscales Personalized
      stigma, Disclosure concerns, Concerns about public attitudes, and Negative self
      image. Differential Item Functioning (DIF) for these items was assessed using
      hybrid ordinal regression-IRT technique. When DIF was detected, the cumulative
      impact of DIF on individual subscale scores was evaluated. RESULTS: DIF was
      detected for 9 items within, between, or across cohorts, but the DIF was
      negligible in general. Detected DIF between the Swedish and Indian cohorts had a
      cumulative salient impact on individual scores for the subscale Disclosure
      Concerns; Disclosure concerns were overestimated in the Swedish cohort and both
      over- and underestimated in the Indian cohort. CONCLUSIONS: The items in the 32
      item version of the HIV stigma scale did not seem to be particularly prone to
      present DIF. The DIF between the Indian and Swedish cohort for items in the
      subscale Disclosure Concerns could, however, result in both type I and type II
      errors if scores should be compared between the Indian and Swedish cohort.

PMID- 29574528
TI  - MicroRNA expression profile of thyroid nodules in fine-needle aspiration
      cytology: a confirmatory series.
AB  - INTRODUCTION: MiRNAs are small endogenous non-coding RNAs implicated with gene
      expression regulation. Changes in miRNA levels have been reported in thyroid
      cancer. Fine-needle aspiration cytology (FNAC) is the most reliable tool for
      differential diagnosis of thyroid nodules. METHODS: We have analyzed 174 FNAC
      from 168 patients with thyroid nodules for expression levels of 11 miRNAs
      (miRNA197; -187; -181b-3p; -181b-5p; -224; -181a; 146b; -221; -222; -155 and
      miRNA183) known to be up-regulated in cancer tissues compared to benign lesions.
      Expression of miRNAs was analyzed in FNA samples calculating the fold change of
      miRNA expression relative to normal thyroid tissue after normalization to an
      endogenous control. RESULTS: In FNAC, miRNA expression was confirmed to be higher
      in malignant or suspicious for malignancy nodules compared to benign, only for
      miRNA146b, -222 and -221 (fold change expression >= 5). CONCLUSION: In this
      study, we confirmed that a limited set of miRNAs can be used for the differential
      diagnosis of thyroid nodules.

PMID- 29574527
TI  - Treatment of Allergic Rhinitis as a Strategy for Preventing Asthma.
AB  - PURPOSE OF REVIEW: To evaluate the impact of allergic rhinitis (AR) on the
      development of asthma and to update readers on recent literature suggesting that
      early treatment of allergic subjects with immunotherapy may prevent asthma onset.
      RECENT FINDINGS: AR is frequently associated with asthma, leading to the concept
      that these two conditions are different aspects of the same disease. There is
      increasing evidence that AR precedes the onset of asthmatic symptoms and current
      treatment strategies are beneficial in symptom control with no impact prevention.
      There is limited knowledge about the risk factors responsible for the progression
      of AR to asthma, though recent data supports the notion that it is possible to
      prevent asthma onset by allergen immunotherapy. Despite significant advances in
      specific immunotherapy (SIT) therapy strengthening its efficacy in AR and
      possible prevention of progression to asthma, the adoption of this therapeutic
      strategy is still restricted in comparison to therapies directed towards
      treatment of AR symptoms. Unlike corticosteroids and other symptomatic therapies,
      the benefit of SIT treatment in allergic individuals has been shown to prevent
      the development of allergic conditions. Hence, large well-conducted randomized
      clinical trials with long-term efficacy of SIT are required to confirm or refute
      the concept that SIT may abrogate the progression of AR to asthma in patients.

PMID- 29574530
TI  - Cutaneous metastases of infantile choriocarcinoma can mimic infantile hemangioma
      both clinically and radiographically.
AB  - Infantile metastatic choriocarcinoma is a rare tumor of placental origin that can
      be observed with or without maternal metastases. A single cutaneous mass may be
      the only clinically observed sign. Reports of imaging findings are scarce given
      the extreme rarity of the tumor, and the disease can be rapidly fatal in the
      absence of prompt diagnosis. In order to promote timely consideration for this
      malignancy as a differential consideration in the approach to skin lesions in
      infancy, we present the findings of this neoplasm in an infant. While imaging and
      clinical characteristics similar to infantile hemangioma were demonstrated at
      presentation, biopsy and further radiologic investigation revealed multifocal
      metastatic choriocarcinoma. This case also highlights important differences
      between these entities, as the T2 hyperintensity and contrast enhancement
      observed with this choriocarcinoma were predominantly peripheral in location.

PMID- 29574529
TI  - Predictors of fat-free mass loss 1 year after laparoscopic sleeve gastrectomy.
AB  - PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is one of the most frequently
      performed bariatric surgery interventions because of its safety and efficacy.
      Nevertheless, concerns have been raised on its detrimental effect on patient
      nutritional state that can ultimately lead to the loss of fat-free mass (FFM).
      There is interest in identifying predictors for the early identification of
      patients at risk of this highly unwanted adverse because they could benefit of
      nutritional preventive interventions. Therefore, we investigated whether
      anthropometric parameters, body composition or resting energy expenditure (REE)
      measured before surgery could predict FFM loss 1 year after LSG. METHODS: Study
      design was retrospective observational. We retrieved data on body weight, BMI,
      body composition and REE before and 1 year after LSG from the medical files of 36
      patients operated on by LSG at our institutions. Simple regression, the Oldham's
      method and multilevel analysis were used to identify predictors of FFM loss.
      RESULTS: Averaged percentage FFM loss 1 year after LSG was 17.0 +/- 7.7% with
      significant differences between sexes (20.8 +/- 6.6 in males and 12.2 +/- 6.1% in
      females, p < 0.001). FFM loss was strongly predicted by pre-surgery FFM and this
      effect persisted also after correcting for the contribution of sex. CONCLUSIONS:
      High FFM values before surgery predict a more severe FFM loss after LSG. This
      factor could also account for the higher FFM loss in men than in women. Our
      finding could help in the early identification of patient requiring a nutritional
      support after LSG.

PMID- 29574531
TI  - Trauma, Discrimination, and Psychological Distress Across Vietnamese Refugees and
      Immigrants: A Life Course Perspective.
AB  - Vietnamese Americans are a heterogeneous group with varied migration histories.
      The life course perspective (LCP) suggests that different migration histories
      (immigrant vs. refugee) may affect their psychological health. Using Vietnamese
      refugee (n = 291) and immigrant (n = 211) subsamples from the National Latino and
      Asian American Study, selected LCP factors relevant to foreign-born Vietnamese
      were examined for their associations with psychological distress. Two separate
      regressions were conducted to examine differential factors across the subgroups.
      Results showed that sex, age at immigration, and pre- and post-migration traumas
      were significant factors for refugees. Among immigrants, only racial
      discrimination was significant factor. The results suggest that applying LCP
      among Vietnamese Americans helps to discern factors associated with their
      psychological distress outcomes depending on their initial immigration status.
      The results also indicate that healthcare professionals should consider the
      migration background of foreign-born Vietnamese in screening for potential
      psychological issues, particularly around their trauma history and discriminatory
      experiences.

PMID- 29574532
TI  - An Examination of Peer-Delivered Parenting Skills Programs Across New York State.
AB  - Peers are an important adjunct to the public mental health service system, and
      are being increasingly utilized across the country as a cost-effective solution
      to workforce shortages. Despite the tremendous growth of peer-delivered support
      over the past two decades, it has only been within the past few years that peer
      programs have been the subject of empirical inquiry. The purpose of this study
      was to examine the prevalence and characteristics of peer-delivered parenting
      programs across the New York State public mental health service system. We
      surveyed 46 family peer organizations across New York State regarding their
      delivery of structured peer-delivered parenting programs. Thirty-four (76%)
      completed the questionnaire, and of them, 18 (53%) delivered a parenting program.
      Subsequent interviews with seven of the 18 organizations revealed peer
      organizations had been delivering eight unique parenting programs for upwards of
      two decades. Additionally, organizations offered multiple supports to families to
      participate. Training, supervision, and issues around fidelity are discussed, as
      well as the implications of this study for states utilizing a peer workforce.

PMID- 29574533
TI  - Correction to: Oxford House Residents' Attitudes Toward Medication Assisted
      Treatment Use in Fellow Residents.
AB  - The original version of this article unfortunately contained a mistake in the
      author group, where co-authors Isabel Dovale, Noah Gelfman and Sarah Callahan
      were missed to include and Brandon Isler should be removed from the author group.

PMID- 29574534
TI  - To die or not to die: death signaling in nonalcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an emerging liver disease worldwide.
      In subset of patients, NAFLD progresses to its advanced form, nonalcoholic
      steatohepatitis (NASH), which is accompanied with inflammation and fibrosis.
      Saturated free fatty acid-induced hepatocyte apoptosis is a feature of NASH.
      Death signaling in NASH does not always result in apoptosis, but can
      alternatively lead to the survival of cells presenting signs of pro-inflammatory
      and pro-fibrotic signals. With the current lack of established treatments for
      NASH, it is important to understand the molecular mechanisms responsible for
      disease development and progression. This review focuses on the latest findings
      in hepatocyte death signaling and discusses possible targets for intervention,
      including caspases, death receptor and c-Jun N-terminal kinase 1 signaling,
      oxidative stress, and endoplasmic reticulum stress, as well as epigenomic
      factors.

PMID- 29574535
TI  - Epigenetics of Skeletal Diseases.
AB  - PURPOSE OF REVIEW: Epigenetic mechanisms modify gene activity in a stable manner
      without altering DNA sequence. They participate in the adaptation to the
      environment, as well as in the pathogenesis of common complex disorders. We
      provide an overview of the role of epigenetic mechanisms in bone biology and
      pathology. RECENT FINDINGS: Extensive evidence supports the involvement of
      epigenetic mechanisms (DNA methylation, post-translational modifications of
      histone tails, and non-coding RNAs) in the differentiation of bone cells and
      mechanotransduction. A variety of epigenetic abnormalities have been described in
      patients with osteoporosis, osteoarthritis, and skeletal cancers, but their
      actual pathogenetic roles are still unclear. A few drugs targeting epigenetic
      marks have been approved for neoplastic disorders, and many more are being
      actively investigated. Advances in the field of epigenetics underscore the
      complex interactions between genetic and environmental factors as determinants of
      osteoporosis and other common disorders. Likewise, they help to explain the
      mechanisms by which prenatal and post-natal external factors, from nutrition to
      psychological stress, impact our body and influence the risk of later disease.

PMID- 29574536
TI  - Does Maternal Exposure to Secondhand Tobacco Smoke During Pregnancy Increase the
      Risk for Preterm or Small-for-Gestational Age Birth?
AB  - Introduction While associations between active smoking and various adverse birth
      outcomes (ABOs) have been reported in the literature, less is known about the
      impact of secondhand smoke (SHS) on many pregnancy outcomes. Methods We examined
      the relationship between maternal exposure to SHS during pregnancy and preterm (<
      37 weeks gestation) and small-for-gestational age (SGA; assessed using sex-,
      race/ethnic-, and parity-specific growth curves) singleton births using non
      smoking controls from the National Birth Defects Prevention Study (1997-2011).
      Multivariable logistic regression models for household, workplace/school, and
      combined SHS exposure-controlled for maternal education, race/ethnicity, pre
      pregnancy body mass index, and high blood pressure-were used to estimate adjusted
      odds ratios (aORs) and 95% confidence intervals (CIs). Interaction was assessed
      for maternal folic acid supplementation, alcohol use, age at delivery, and infant
      sex. Results Infants of 8855 mothers were examined in the preterm birth analysis
      with 666 (7.5%) categorized as preterm, 574 moderately preterm (32-36 weeks), and
      92 very preterm (< 32 weeks). For the SGA analysis, infants of 8684 mothers were
      examined with 670 (7.7%) categorized as SGA. The aORs for mothers reporting both
      household and workplace/school SHS were elevated for preterm (aOR 1.99; 95% CI
      1.13-3.50) and moderately preterm birth (32-36 weeks) (aOR 2.17; 95% CI 1.22
      3.88). No results for the SGA analysis achieved significance, nor was evidence of
      interaction evident. Conclusion The findings suggest an association between SHS
      from multiple exposure sources and preterm birth, but no evidence for association
      with SGA births. Continued study of SHS and ABOs is needed to best inform public
      health prevention programs.

PMID- 29574537
TI  - Percutaneous Needle Aspiration of a Partially Deflated Intragastric Balloon: a
      Forgotten Modality? Review of the Literature.

PMID- 29574539
TI  - Cervical Cancer Patients' Willingness and Ability to Serve as Health Care
      Educators to Advocate for Human Papillomavirus Vaccine Uptake.
AB  - Human papillomavirus (HPV) causes nearly all cervical cancer. Only half of
      females and less than half of males receive the recommended HPV vaccine dose.
      This study explores whether cervical cancer patients may serve as health
      advocates to adolescents and their parents in encouraging the uptake of the HPV
      vaccine. The study targeted an opportunity sample of women seen in the gynecology
      oncology clinic with a diagnosis of cervical cancer. During interviews, patients
      were asked about the following: provider conversations regarding cervical cancer,
      knowledge of HPV and the vaccine, discussions with family or friends about the
      causes or prevention of cervical cancer, and whether they would be willing to
      talk with others about the HPV vaccine. Twenty-three interviews were conducted in
      2016-2017. Patients ranged from 28 to 61 years of age. Four team members
      developed a coding list, then used these themes to code the interviews. Six
      themes resulted from the analysis of the transcripts: (1) Expressions of fears,
      questioning effectiveness of vaccine; (2) Low level of health literacy; (3)
      Acquiring health information from television, internet; (4) Provider
      conversations (with patients regarding HPV and the vaccine); (5) Patient stigma
      surrounding cervical cancer; (6) Patients' willingness to serve as a health care
      educator. While cervical cancer patients overall expressed a willingness to serve
      as health care educators, barriers remain. Low health literacy and a lack of
      understanding of the causes of cervical cancer persist. These issues will need to
      be addressed in order for cervical cancer patients to be effective advocates.

PMID- 29574538
TI  - Identifying Factors Underlying the Decision for Sickle Cell Carrier Screening
      Among African Americans Within Middle Reproductive Age.
AB  - Guidelines recommend that African Americans know their sickle cell trait status
      to inform reproductive health decisions. Few studies have applied a behavioral
      theory to identify factors associated with sickle cell trait screening to inform
      intervention targets to increase this behavior. We applied a Sickle Cell Trait
      Screening Framework to identify factors associated with African Americans'
      intention to ask for sickle cell trait screening. Participants (N = 300), ages 18
      to 35, completed a cross-sectional survey. A three-step sequential ordinary least
      squares regression analysis identified factors influencing intention. Results
      indicated socio-demographic factors (age, education), knowledge and fear beliefs
      (screening knowledge, perceived threat), and reasoned action approach (RAA)
      constructs were associated with intention. RAA constructs influenced intention
      over knowledge and fear beliefs with an increase in R2 of .468. Perceived
      behavioral control was more predictive of intention (beta = .576, p < .001).
      Attitude and perceived norm also had significant weights (beta = .325 and beta =
      .192, both p < .001, respectively). Findings from this study can inform
      strategies (e.g., eliminating costs associated with screening, reducing fear of
      painful tests) to increase sickle cell trait screening among African Americans.
      Ultimately, more sickle cell carriers will become aware of their trait status and
      be able to make informed reproductive health decisions.

PMID- 29574540
TI  - Supporting Latina Breast Health with Community-based Navigation.
AB  - Latina women continue to face disproportionate breast cancer risk and well
      documented breast health care barriers in Philadelphia. In response to breast
      health needs among Latinas in Philadelphia, a health-focused community-based
      organization, in partnership with a network of social and health service
      providers, began offering community-based navigation in 2005. Later, through
      funding from a federal agency, the organization launched the Naveguemos con Salud
      (NCS) Breast Health Partnership Project from 2010 to 2013. NCS offered breast
      health awareness and education to a broad audience of Latinas in Philadelphia and
      community-based navigation services to all interested in accessing a clinical
      breast exam (CBE) and/or mammogram. A 2017 survey revisited breast health needs
      among the same core population to inform next steps. Here, we explore how
      findings and lessons learned from a past program and an assessment of current
      needs can inform future community-clinical linkage and community-based navigation
      to improve access to breast cancer screening and a continuum of care for Latinas.

PMID- 29574541
TI  - Speech Therapy as Treatment for Supragastric Belching.
AB  - The purpose of this study was to describe a newly developed speech therapy
      program as an innovating therapeutic approach and to assess the results of this
      intervention in patients with supragastric belching. This is a retrospective
      analysis of prospectively gathered data from 73 patients with supragastric
      belching who were treated with speech therapy between 2007 and 2017. Of these, 48
      were included for evaluation of therapy. Thirty patients had supragastric
      belching proven by 24-h impedance measurements. Eighteen patients were diagnosed
      by an experienced speech language pathologist as having supragastric belching
      according to precise criteria. Speech therapy consists of explanation, creating
      awareness of esophageal air influx and exercises to discontinue the supragastric
      belching mechanism. Therapy effect was measured by comparing visual analogue
      scale (VAS) scores on belching and related symptoms. The median symptom duration
      at the start of therapy was 2 years. Supragastric belching symptoms decreased
      significantly with a total median VAS score of 406 (291-463) prior to treatment
      and a median VAS score of 125 (17-197) following treatment. Forty patients (83%)
      had a sufficient to major result with a median therapy duration of 3 months and
      ten sessions. Speech therapy was an effective treatment in the majority of
      patients with supragastric belching.

PMID- 29574542
TI  - Factors Associated with Assignment of Therapeutic Homework in a Large Public
      Children's Mental Health System.
AB  - Therapeutic homework is a fundamental skill-building component of the majority of
      evidence-based therapies and is associated with better treatment outcomes.
      However, it is rarely utilized in public mental health settings. To determine
      barriers to homework use and identify predictors of clinicians' assignment of
      homework, an online survey was administered to 267 clinicians in a large diverse
      public mental health system. Clinicians who were younger, licensed, whose
      supervisors asked about homework and whose clients completed their homework more
      frequently were predictors of greater homework utilization. The survey results
      are discussed and a novel idea to increase the use of homework is introduced.

PMID- 29574543
TI  - Examining Mechanisms and Moderators of the Relationship Between Discriminatory
      Health Care Encounters and Attempted Suicide Among U.S. Transgender Help-Seekers.
AB  - This study examined how experiences of service denial and discrimination in three
      health care settings-doctors' offices, emergency rooms, and mental health clinics
      might contribute to attempted suicide among transgender adults. Mechanisms of
      this relationship were examined, including treatment receipt and the use of
      substances to cope with mistreatment. Perceived emotional social support was also
      tested as a potential protective factor against the deleterious effects of
      service denial and discrimination on treatment receipt, substance use, and
      attempted suicide. The analysis included 4190 respondents from the National
      Transgender Discrimination Survey. Structural equation modeling was employed to
      test hypothesized relationships. Being denied a greater number of services and
      discriminated against in more settings were associated with lower levels of
      treatment receipt. Service denial was also correlated with increased rates of
      coping-motivated substance use and elevated rates of attempted suicide. Treatment
      receipt mediated the relationships between service denial/discrimination and
      substance use. Substance use mediated the relationship between treatment receipt
      and attempted suicide. Higher levels of support were protective to treatment
      receipt when denied services in one setting, but no longer retained protective
      effects when denied in two or three settings. Results have critical implications
      for service access and delivery and policies that protect transgender help
      seekers in the health care system.

PMID- 29574544
TI  - Preservation of renal function in chronic diabetes by enhancing glomerular
      glucose metabolism.
AB  - Diabetic nephropathy (DN) affects approximately 30-40% of patients with type 1
      (T1DM) and type 2 diabetes (T2DM). It is a major cause of end-stage renal disease
      (ESRD) for the developed world. Hyperglycemia and genetics are major causal
      factors for the initiation and progression of DN. Multiple abnormalities in
      glucose and mitochondrial metabolism induced by diabetes likely contribute to the
      severity of DN. Recent clinical studies in people with extreme duration of T1DM
      (> 50 years, Joslin Medalist Study) have supported the importance of endogenous
      protective factors to neutralize the toxic effects of hyperglycemia on renal and
      other vascular tissues. Using renal glomeruli from these patients (namely
      Medalists) with and without DN, we have shown the importance of increased
      glycolytic flux in decreasing the accumulation of glucose toxic metabolites,
      improving mitochondrial function, survival of glomerular podocytes, and reducing
      glomerular pathology. Activation of a key glycolytic enzyme, pyruvate kinase M2
      (PKM2), resulted in the normalization of renal hemodynamics and mitochondrial and
      glomerular dysfunction, leading to the mitigation of glomerular pathologies in
      several mouse models of DN.

PMID- 29574545
TI  - Central sensitization is a risk factor for wound complications after primary
      total knee arthroplasty.
AB  - PURPOSE: Postoperative wound complication is a significant risk factor for
      subsequent deep periprosthetic joint infection after total knee arthroplasty
      (TKA). Central sensitization is an abnormal enhancement of pain mechanism
      involving the central nervous system. Although psychological disorder is widely
      considered as a risk factor, the relationship between central sensitization and
      wound complication is currently unclear. Therefore, the purpose of this study was
      to investigate whether central sensitization was associated with high wound
      complication rate after primary TKA. MATERIALS AND METHODS: Between January and
      June 2016, 161 patients undergoing unilateral TKA were prospectively divided into
      two groups based on central sensitization inventory score of 40 points after
      excluding cases with known risk factors such as physical comorbidities, health
      related behaviors, and psychological disorders. Group 1 consisted of 112 patients
      (112 knees) whose central sensitization inventory score was < 40 points and group
      2 consisted of 49 patients (49 knees) whose central sensitization inventory score
      was >= 40 points. Wound complications were defined as wound dehiscence, suture
      granuloma, prolonged wound oozing after postoperative day 5, significant hematoma
      formation, or surgical site infection recorded during the initial 90-day
      postoperative period. Demographic data, visual analog scale (VAS), central
      sensitization inventory score, and wound complications were compared between the
      two groups. RESULTS: Wound complications developed in 3 (2.7%) knees in group 1
      and 14 (28.6%) knees in group 2 (p < 0.001). Multivariate logistic regression
      analysis showed that the odds of postoperative wound complications were increased
      15.7 times in patients with central sensitization inventory score >= 40 (95% CI
      4.1-60.0, p < 0.001). CONCLUSION: Central sensitization is a risk factor for the
      development of postoperative wound complication after primary TKA. LEVEL OF
      EVIDENCE: II.

PMID- 29574546
TI  - Graft bending angle affects allograft tendon maturity early after anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: The aim of this study was to clarify the association of the anterior
      cruciate ligament (ACL) graft bending angle and graft maturity of autograft and
      allograft tendons using high-resolution MRI. METHODS: Patients with unilateral
      ACL reconstruction were invited to participate in this study, and they were
      examined using a 3.0-T MRI scan at 3, 6 and 12 months after the operation.
      Anatomic single-bundle ACL reconstruction was performed on 48 patients using the
      trans-portal technique, including 28 with autograft hamstring tendons and 20 with
      allograft tendons. To evaluate graft healing, the signal/noise quotient (SNQ) was
      measured in four regions of interest (ROIs) of the femoral tunnel, proximal,
      midsubstance and distal ACL grafts. The graft bending angle was defined as the
      angle between the femoral bone tunnel and the line connecting the femoral and
      tibial tunnel apertures. Graft SNQ and graft bending angle were assessed at 3, 6
      and 12 months postoperatively, and the association between SNQ and the average
      graft bending angle was analyzed. RESULTS: Generally, the mean graft bending
      angle of this cohort increased gradually with time. The SNQ value of each graft
      region increased from 3 to 6 months and then decreased from 6 to 12 months. In
      the whole cohort, the graft bending angle had a significant positive association
      with graft SNQ in the femoral tunnel or proximal site. In the allograft subgroup,
      the graft bending angle had a significant positive association with the graft SNQ
      in the femoral tunnel or proximal site at 6 months after surgery, while there was
      no association between the graft bending angle and SNQ at 12 months. In the
      autograft subgroup, the graft bending angle had a significant positive
      association with graft SNQ in the femoral tunnel or proximal site at 12 months
      after surgery. CONCLUSION: Generally, the graft bending angle was correlated with
      a high signal intensity of the proximal graft in the early postoperative period
      for allograft tendons and in the late postoperative period for allograft tendons.
      This suggests that the biomechanical effect from the graft bending angle on graft
      healing may be different for allografts and autografts after ACL reconstruction.
      LEVEL OF EVIDENCE: III.

PMID- 29574547
TI  - Hip capsular thickness correlates with range of motion limitations in
      femoroacetabular impingement.
AB  - PURPOSE: Femoroacetabular impingement (FAI) is a clinical entity of the hip
      causing derangements in range of motion, pain, gait, and function. Computer
      assisted modeling and clinical studies suggest that patients with FAI have
      increased capsular thickness compared to those without.A retrospective chart
      review was performed to assess relationships between capsular thickness, hip
      range of motion, and demographic factors in patients with FAI. METHODS: Local
      Research Ethics Board approval was obtained to extract electronic medical records
      for 188 patients at a single institution who had undergone hip arthroscopy.
      Procedures were performed from 2009 to 2017 by a single, fellowship-trained,
      board-certified sports medicine orthopaedic surgeon. Inclusion criteria were
      preoperative hip range of motion testing, positive clinical impingement testing,
      and magnetic resonance imaging (MRI) of the affected hip. Patient demographics,
      hip range of motion, and time to surgery were recorded. MRIs were reviewed by a
      board-certified musculoskeletal radiologist blinded to clinical data. Maximum
      thickness of the anterior hip capsule was measured in axial, axial oblique, and
      sagittal oblique sequences. Anterior capsular thickness was also measured at the
      level of the femoral head-neck junction in axial sequences (axial midline).
      RESULTS: Axial midline capsular thickness was negatively correlated with hip
      flexion (r = - 0.196, p = 0.0042) and internal rotation (r = - 0.143, p =
      0.0278). Significant differences were seen between genders in axial midline
      thickness (5.3 +/- 1.4 mm males/4.8 +/- 1.3 mm females, p = 0.0079), flexion (113
      degrees  +/- 18 degrees  males/120 degrees  +/- 17 degrees  females, p = 0.0029),
      and internal rotation (23 degrees  +/- 13 degrees  males/29 degrees  +/- 12
      degrees  females, p = 0.0155). Significant differences also existed between side
      affected in flexion (116 degrees  +/- 17 degrees  right/119 degrees  +/- 17
      degrees  left, p = 0.0396) and internal rotation (26 degrees  +/- 12 degrees 
      right/29 degrees  +/- 13 degrees  left, p = 0.0029). Positive correlation was
      observed between axial oblique capsular thickness and flexion (r = 0.2345) (p =
      0.0229). CONCLUSIONS: Increased anterior hip capsular thickness at the femoral
      head-neck correlates with limitations in hip range of motion in FAI. The strength
      of this relationship may be affected between pathologies, genders, and affected
      side. Pathologic thickening of the hip capsule may contribute to restricted hip
      mobility on clinical examination, and elucidation of this relationship may
      provide guidance into capsular management during hip arthroscopy. LEVEL OF
      EVIDENCE: 4, retrospective case series.

PMID- 29574548
TI  - Low rates of patients meeting return to sport criteria 9 months after anterior
      cruciate ligament reconstruction: a prospective longitudinal study.
AB  - PURPOSE: The purpose of the current prospective study was to assess the changes
      over time in patients tested at 6 months and 9 months after anterior cruciate
      ligament reconstruction (ACLR) with a return to sport (RTS) test battery. It was
      hypothesized that more patients passed RTS criteria at 9 months compared to 6
      months. METHODS: Sixty-two ACLR patients performed a test battery at an average
      of 6.5 +/- 0.7 and 9.5 +/- 0.9 months after ACLR. All patients underwent a
      standardized rehabilitation protocol. The test battery consisted of the following
      tests: a jump-landing task assessed with the Landing Error Scoring System (LESS),
      three single-leg hop tasks (single-leg hop test, triple-leg hop test, side hop
      test), isokinetic quadriceps and hamstring strength at 60, 180 and 300 degrees /s
      and two questionnaires (IKDC and ACL-RSI). Cut off criteria were set as Limb
      Symmetry Index (LSI) > 90% (for isokinetic strength and for single-leg hop
      tasks), LESS < 5, IKDC score within 15th percentage of healthy subjects and ACL
      RSI > 56 respectively. RESULTS: At 6 months, two patients (3.2%) passed all
      criteria. At 9 months, seven patients (11.3%) passed all criteria. Patients
      improved in all RTS criteria over time except for the IKDC score. Twenty-nine
      patients (46.8%) did not pass the strength criterion at 60 degrees /s at 9 months
      after ACLR. CONCLUSIONS: The percentages of patients passing all RTS criteria
      were low at both 6 and 9 months after ACLR. Quadriceps strength revealed
      persistent deficits and the lack of improvement in the IKDC score questionnaires
      shows insufficient self-reported knee function for RTS. LEVEL OF EVIDENCE: III.

PMID- 29574549
TI  - Simultaneous, same-anaesthetic bilateral total knee arthroplasty has low
      mortality and complication rates.
AB  - PURPOSE: The benefits of simultaneous bilateral total knee arthroplasty (SBTKR)
      include reduced hospital costs, single anaesthetic exposure and in many cases is
      also the patient's preference. Despite these potential benefits, risk-adversity
      with respect to assumed complications and mortality make it difficult for the
      orthopaedic surgeon and patient to make an informed decision. This study aimed to
      address the inconsistencies and lack of consensus in previous literature
      regarding the short-term complications and clinical safety of SBTKR in patients
      with end-stage knee osteoarthritis (OA). METHODS: A cohort of 950 knees (475
      patients) undergoing surgery between 2008 and 2013 was extracted from a
      prospectively collected clinical database and retrospectively linked to the
      Australian Joint Replacement Registry and hospital records. Patients underwent
      sequential SBTKR by their treating surgeon under one anaesthetic. Basic
      demographic data and outcome data including complications and mortality were
      collected. All data were analyzed using descriptive statistics only. RESULTS: A
      total of 413 patients and 826 knees were included. The average age of the cohort
      was 70 years with range between 46 and 88 years. 50% of patients were female. The
      overall mortality rate during the study follow-up period was 1.9%, with an
      average time to death postoperatively of 23.8 months. There were no cases of
      acute postoperative mortality (< 6 weeks). Medical complication rates were low.
      CONCLUSIONS: In contrast to the higher mortality and complication rates suggested
      in previous literature, this study has demonstrated that SBTKR is safe, with low
      mortality and complication rates under the current surgical protocol. LEVEL OF
      EVIDENCE: IV.

PMID- 29574550
TI  - Light-Sheet Imaging to Elucidate Cardiovascular Injury and Repair.
AB  - PURPOSE OF REVIEW: Real-time 3-dimensional (3-D) imaging of cardiovascular injury
      and regeneration remains challenging. We introduced a multi-scale imaging
      strategy that uses light-sheet illumination to enable applications of
      cardiovascular injury and repair in models ranging from zebrafish to rodent
      hearts. RECENT FINDINGS: Light-sheet imaging enables rapid data acquisition with
      high spatiotemporal resolution and with minimal photo-bleaching or photo
      toxicity. We demonstrated the capacity of this novel light-sheet approach for
      scanning a region of interest with specific fluorescence contrast, thereby
      providing axial and temporal resolution at the cellular level without stitching
      image columns or pivoting illumination beams during one-time imaging. This
      cutting-edge imaging technique allows for elucidating the differentiation of stem
      cells in cardiac regeneration, providing an entry point to discover novel micro
      circulation phenomenon with clinical significance for injury and repair. These
      findings demonstrate the multi-scale applications of this novel light-sheet
      imaging strategy to advance research in cardiovascular development and
      regeneration.

PMID- 29574552
TI  - Production systems of Japanese quail (Coturnix coturnix japonica) in the urban
      communities of southwestern Nigeria.
AB  - The study was conducted to examine the management practices and constraints
      associated with quail production in southwestern Nigeria. Data were collected
      through a survey of 113 quail bird farmers selected by multi-stage sampling
      technique from three states of southwestern Nigeria. Data were analyzed mainly by
      descriptive statistics with values compared across states using relevant
      statistics at certain instances. The results show that quail farming is a
      relatively new enterprise with farmers' average year of experience estimated as
      4.52 years. Production was predominantly for the sale of eggs and table birds
      (46.90%). They were reared under intensive system (87.61%) and in deep litters
      (53.10%). Birds were commonly reared with chicken (71.03% of the farmers).
      Foundation stocks were sourced from commercial farms (33.63%) and hatcheries
      (25.66%), while birds were fed on compounded feed by 73.45% of the farmers in the
      morning and evening (55.75%). Veterinary support services were sought
      occasionally by 76.99% of the farmers while 55.7 and 40.71% of the farmers
      vaccinated and dewormed their birds, respectively. Disease incidence was
      generally low across the states with incidence in 13.27% of the farms with
      associated mortality of 2.05%. Quail eggs and birds were predominantly sold at
      farm gate (81.42%) at average prices of N632.94 per crate and N584.09 per bird
      respectively. Notable constraints were inadequate technical knowledge on feed
      formulation, difficulty in meat processing and marketing, which need to be
      addressed for upscaling the technology.

PMID- 29574553
TI  - Time of feeding and predictability of dry matter and water intake of grasscutters
      fed on grass and supplements containing varying levels of dietary fiber.
AB  - The study evaluated the feeding behavior of growing male grasscutters (Thryonomys
      swinderianus) fed freshly cut Panicum maximum, supplemented with pelletized
      concentrates containing varying levels of dietary fiber. In a two-stage 4 * 4
      Latin square arrangement, the relationships between water and dry matter intakes
      as influenced by dietary characteristics were investigated by offering
      supplements either at 09:00 h (morning) during the first stage or at 17:00 h
      (evening) during the second. Each test period lasted for 14 days with a 1-week
      rest period between changeovers. Time of feeding significantly (P < 0.05)
      affected total dry matter intake (DMI) and intake of the supplements, with the
      total DMI increasing by 21% when the diets were offered in the evening relative
      to when offered in the morning. Regression analyses showed significant (P < 0.05)
      correlations between dry matter (DM) and water intakes against some dietary
      characteristics. The current study has shown that crude fiber (CF) inclusion of
      up to 14% in pelletized supplements for growing grasscutters consuming a basal
      diet with CF up to 31% may not affect feed and water intake, as well as
      acceptability of the feed. However, feeding such supplements in the evening could
      stimulate higher feed intake. Also, dietary DM better predicted DMI compared to
      the other dietary characteristics.

PMID- 29574554
TI  - Chimpanzees prioritise social information over pre-existing behaviours in a group
      context but not in dyads.
AB  - How animal communities arrive at homogeneous behavioural preferences is a central
      question for studies of cultural evolution. Here, we investigated whether
      chimpanzees (Pan troglodytes) would relinquish a pre-existing behaviour to adopt
      an alternative demonstrated by an overwhelming majority of group mates; in other
      words, whether chimpanzees behave in a conformist manner. In each of five groups
      of chimpanzees (N = 37), one individual was trained on one method of opening a
      two-action puzzle box to obtain food, while the remaining individuals learned the
      alternative method. Over 5 h of open access to the apparatus in a group context,
      it was found that 4/5 'minority' individuals explored the majority method and
      three of these used this new method in the majority of trials. Those that
      switched did so after observing only a small subset of their group, thereby not
      matching conventional definitions of conformity. In a further 'Dyad' condition,
      six pairs of chimpanzees were trained on alternative methods and then given
      access to the task together. Only one of these individuals ever switched method.
      The number of observations that individuals in the minority and Dyad individuals
      made of their untrained method was not found to influence whether or not they
      themselves switched to use it. In a final 'Asocial' condition, individuals (N =
      10) did not receive social information and did not deviate from their first
      learned method. We argue that these results demonstrate an important influence of
      social context upon prioritisation of social information over pre-existing
      methods, which can result in group homogeneity of behaviour.

PMID- 29574551
TI  - The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in
      Chronic Spontaneous Urticaria.
AB  - Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its
      prevalence, the neuropathology of CSU is uncertain. In this study, we explored
      resting state functional connectivity (rs-FC) changes in CSU, as well as how the
      symptom changes following intervention can modulate rs-FC. Forty patients and 40
      healthy controls (HCs) were recruited. Following an intervention, 32 patients
      participated in a second scan approximately 6 weeks after the first scan.
      Compared with healthy controls, CSU subjects exhibited higher regional
      homogeneity (ReHo) values in the cerebellum, which were positively associated
      with urticaria activity scores over 7 days (UAS7) at baseline. After an
      intervention accompanied with clinical improvement, we found that ReHo values
      decreased at the cerebellum and increased at the bilateral primary somatosensory
      cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the
      cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions
      when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal
      cortex and right sensorimotor region following the intervention. The improvement
      rate values were positively associated with reduced rs-FC values in the two
      regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited
      decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following
      the intervention. These results demonstrate the altered cerebellar activity and
      cerebellum-reward-sensorimotor loops in CSU.

PMID- 29574555
TI  - Paediatric lateral condyle fractures: a systematic review.
AB  - INTRODUCTION: Lateral condyle fractures of the humerus are common paediatric
      fractures. However, no conclusive statement has been made about their risk of
      complications, the management and epidemiology. MATERIALS AND METHODS: A
      systematic review was conducted according to PRISMA guidelines. All studies with
      paediatric lateral condyle fracture were included, with 2440 children. RESULTS:
      Most fractures had union, with 0.9% delayed union, 1.6% non-union and 1.5%
      malunion. Complications included valgus deformities (6.1%), varus deformities
      (7.8%), flexion loss (9.7%), extension loss (11.5%), prominent lateral condyle
      (27.3%), fishtail deformity (14.3%), avascular necrosis (1.7%), premature
      epiphyseal closure (5.4%) and neurological deficits (10.6%). Risk factors of
      complications include concomitant ipsilateral upper limb fractures,
      classification by Milch or Jakob, fracture displacement, fixation device, and
      inappropriate diagnosis and management. CONCLUSIONS: It is recommended for
      fractures that are non-displaced on all radiographic views to be managed
      conservatively, while displaced fractures of > 2 mm requires surgical
      intervention. Minimally displaced fractures could be treated conservatively,
      though follow-up is recommended to detect displacement. Radiographs are also
      recommended at 1-week follow-up, with serial radiographs having no clinical
      significance. Kirschner wires or lag screws could be employed, and it is
      recommended that the Kirschner wires be left exposed and removed when there is
      clinical and radiographic evidence of fracture consolidation, typically at the 6
      week interval. These fractures need close follow-up.

PMID- 29574556
TI  - Fatigue, as measured using the Modified Fatigue Impact Scale, is a predictor of
      processing speed improvement induced by exercise in patients with multiple
      sclerosis: data from a randomized controlled trial.
AB  - BACKGROUND: Few studies have evaluated the impact of physical activity (PA) on
      cognition and fatigue, and none have considered the effects of PA on the
      relationship between cognition and fatigue. OBJECTIVES: We evaluated the effect
      of PA in people with multiple sclerosis (pwMS) in a 6-month-long single-blind
      randomized controlled trial. We focused on the impact of exercise on cognition,
      fatigue, and the relationship between cognition and fatigue. METHODS: We
      recruited pwMS, who were then randomly assigned 1:1 to either a PA protocol group
      or a control group (CG). All patients underwent assessments using the Brief
      International Cognitive Assessment for Multiple Sclerosis including symbol digit
      modality test (SDMT), Berg Balance Scale (BBS), gait analysis, 6-Minute Walk
      Test, Timed Up and Go (TUG) test, and the Modified Fatigue Impact Scale (MFIS) at
      the beginning of the study (T0), at the end of the study (EOS) 24 weeks after T0,
      and at 24 weeks following the EOS (FU). RESULTS: A Wilcoxon test revealed a
      significant effect of exercise in the PA group, but not in the CG. Significant
      differences between T0 and EOS were found in the spatiotemporal parameters of
      gait, and performance on the SDMT, TUG, BBS, and MFIS. These differences were
      also present during the FU period. A regression model revealed that the baseline
      MFIS score predicted processing speed improvement (R2 = 0.65, p < 0.01), as the
      SDMT T score increased by 0.3 for each one-unit increase in the MFIS score at T0.
      CONCLUSION: PA affects multiple aspects of the pathology in pwMS. Patients with
      greater fatigue must not be discouraged from exercise, as they may greatly
      benefit from PA. Specifically, PA was shown to improve information processing
      speed.

PMID- 29574558
TI  - Defining the abdominal radiologist based on the current U.S. job market.
AB  - PURPOSE: The purpose of the study is to characterize current practice patterns of
      abdominal radiologists based on work descriptions within job postings on numerous
      national radiology specialty websites. METHODS: Job postings for either
      "abdominal" or "body" radiologists were searched weekly on five society websites
      (SAR, SCBT-MR, ARRS, ACR, RSNA) over a 1-year period. Postings were reviewed for
      various characteristics. RESULTS: Nine hundred and sixteen total ads for 341
      unique abdominal radiologist positions were reviewed (34.6% academic, 64.2%
      private practice, 1.2% other). Postings occurred most commonly in March (12.3%)
      and least commonly in November (4.8%). States with most positions were Florida
      (27), California (26), and New York (24). Of postings delineating expectations of
      specific abdominal modalities, 67.4% mentioned MRI, 58.5% ultrasound, 41.1%
      fluoroscopy, 14.3% PET, and 54.0% interventions. Additional non-abdominal
      expectations included general radiology (28.7%), breast imaging (21.1%), and
      general nuclear medicine (9.7%). Additional skills included prostate MRI (7.0%),
      OBGYN ultrasound (5.0%), and CT colonoscopy (2.6%). 79.2% required an abdominal
      imaging fellowship (specifically a body MRI fellowship in 4.1%). CONCLUSION: By
      using job postings for abdominal radiologists, we have taken a practical approach
      to characterizing the current status of this subspecialty, reflecting recent job
      expectations and requirements. The large majority of positions required a body
      fellowship, and the positions commonly entailed a variety of skills beyond non
      invasive diagnostic abdominal imaging. Of note, expectations of considerable
      minorities of positions included abdominal interventions, general radiology, and
      breast imaging. These insights may guide the development of abdominal radiology
      fellowships and mini-fellowships, as well as assist radiologists entering or
      returning to the job market.

PMID- 29574557
TI  - miRNAs control HAM1 functions at the single-cell-layer level and are essential
      for normal embryogenesis in Arabidopsis.
AB  - KEY MESSAGE: miR171a controls HAM1 functions within the protodermal cells of the
      embryo, and these controls are essential for normal embryogenesis in Arabidopsis.
      Arabidopsis thaliana miR171a is known to bind to and cleave mRNAs of three HAIRY
      MERISTEM (HAM) genes that encode members of the GRAS family transcriptional
      regulators. The molecular functions of the HAM genes are still being elucidated
      in Arabidopsis. However, detailed expression patterns of miR171a and the effects
      of the failure of miR171a to suppress HAM genes were unknown till now. Here, we
      show the detailed expression patterns of miR171a and HAM1 using green fluorescent
      protein and confocal scanning microscopy. Our observations revealed that miR171a
      was expressed in the surface cell layer of the embryo and shoot apical meristem,
      and it controlled HAM1 functions. To determine the impact of the failure of
      miR171a to suppress of HAM1, we introduced seven synonymous mutations into the
      miR171a target site of the HAM1 gene (modified HAM1, mHAM1) and generated
      transgenic plants that had mHAM1 driven by HAM1 native promoter. The mHAM1
      transgenic plants showed organogenic defects. These results indicate that the
      control of HAM1 functions at the single-cell-layer level by miR171a is essential
      for proper organ formation in Arabidopsis.

PMID- 29574559
TI  - How Do Storms Affect Asthma?
AB  - PURPOSE OF REVIEW: There are observations in various geographical areas that
      thunderstorms occurring during pollen seasons can induce severe asthma attacks in
      pollinosis patients. RECENT FINDINGS: An accredited hypothesis explaining the
      association between thunderstorms and asthma suggests that storms can concentrate
      pollen grains at ground level, which may then release allergenic particles of
      respirable size in the atmosphere after their imbibition of water and rupture by
      osmotic shock. During the first 20-30 min of a thunderstorm, patients affected by
      pollen allergy may inhale a high quantity of the allergenic material that is
      dispersed into the atmosphere as a bioaerosol of allergenic particles, which can
      induce asthmatic reactions, often severe. Subjects without asthma symptoms, but
      affected by seasonal rhinitis can also experience an asthma attack. A key message
      is that all subjects affected by pollen allergy should be alerted to the danger
      of being outdoors during a thunderstorm in the pollen season, as such events may
      be an important cause of severe asthma exacerbations. In light of these
      observations, it is useful to predict thunderstorms and thus minimize
      thunderstorm-related events. Patients with respiratory allergy induced by pollens
      and molds need to be informed about a correct therapeutic approach of bronchial
      asthma by inhalation, including the use of bronchodilators and inhaled
      corticosteroids. The purpose of this review is to focalize epidemiological,
      etiopathogenetic, and clinical aspects of thunderstorm-related asthma.

PMID- 29574560
TI  - In-house validation of a rapid and efficient procedure for simultaneous
      determination of ergot alkaloids and other mycotoxins in wheat and maize.
AB  - A fundamental step in addressing the global problem of mycotoxins is the
      development of highly sensitive, multi-class extraction and detection methods.
      This constitutes a field of research that has in recent years enjoyed a steady
      advance. Such methods, generally based on liquid chromatography coupled to mass
      spectrometry, are widely reported successfully detecting various mycotoxins in
      different food and feed samples. In this work, an innovative approach to multi
      class mycotoxin control is proposed, offering specific advantages: a broader
      inclusion of more mycotoxin classes, robust and thorough extraction for all
      target compounds despite their varied chemical properties, and determination of
      all analytes from a single injection. The method involved the extraction and
      quantification of the main mycotoxins produced by Aspergillus, Fusarium, and
      Penicillium fungi, as well as their reported derivatives, together with 12 other
      compounds most commonly produced by Claviceps purpurea. The popularly reported
      QuEChERS technique has been reduced to a simple "salting-out liquid-liquid
      extraction" (SO-LLE) to obtain the most efficient extraction of the
      aforementioned mycotoxin classes in a very short time. This is in particular
      extremely important in ensuring correct determination of individual ergot
      alkaloids, for which short and robust sample preparation as well as short
      analytical sequences were key for minimizing the epimerization during analysis.
      The analyses of wheat and maize samples were performed using ultra-high
      performance liquid chromatography coupled with tandem mass spectrometry. Matrix
      matched calibration curves were established and limits of quantification were
      below the maximum levels established by the EU regulation. The precision
      (repeatability and intermediate precision) was lower than 13% in all cases and
      recoveries ranged between 60 and 98% in maize and between 62 and 103% in wheat,
      fulfilling the current legislation. The method was applied to study the co
      occurrence of these mycotoxins in wheat (n = 13) and maize (n = 15) samples from
      six European countries. A successful quantification of 23 different mycotoxins,
      from all major classes, in 85% of wheat and 93% of maize samples was achieved.

PMID- 29574561
TI  - Critical assessment of digital PCR for the detection and quantification of
      genetically modified organisms.
AB  - The number of genetically modified organisms (GMOs) on the market is steadily
      increasing. Because of regulation of cultivation and trade of GMOs in several
      countries, there is pressure for their accurate detection and quantification.
      Today, DNA-based approaches are more popular for this purpose than protein-based
      methods, and real-time quantitative PCR (qPCR) is still the gold standard in GMO
      analytics. However, digital PCR (dPCR) offers several advantages over qPCR,
      making this new technique appealing also for GMO analysis. This critical review
      focuses on the use of dPCR for the purpose of GMO quantification and addresses
      parameters which are important for achieving accurate and reliable results, such
      as the quality and purity of DNA and reaction optimization. Three critical
      factors are explored and discussed in more depth: correct classification of
      partitions as positive, correctly determined partition volume, and dilution
      factor. This review could serve as a guide for all laboratories implementing
      dPCR. Most of the parameters discussed are applicable to fields other than purely
      GMO testing. Graphical abstract There are generally three different options for
      absolute quantification of genetically modified organisms (GMOs) using digital
      PCR: droplet- or chamber-based and droplets in chambers. All have in common the
      distribution of reaction mixture into several partitions, which are all subjected
      to PCR and scored at the end-point as positive or negative. Based on these
      results GMO content can be calculated.

PMID- 29574563
TI  - Change in Health Insurance Coverage After Liver Transplantation Can Be Associated
      with Worse Outcomes.
AB  - BACKGROUND: Health insurance coverage changes for many patients after liver
      transplantation, but the implications of this change on long-term outcomes are
      unclear. AIMS: To assess post-transplant patient and graft survival according to
      change in insurance coverage within 1 year of transplantation. METHODS: We
      queried the United Network for Organ Sharing for patients between ages 18-64
      years undergoing liver transplantation in 2002-2016. Patients surviving > 1 year
      were categorized by insurance coverage at transplantation and the 1-year
      transplant anniversary. Multivariable Cox regression characterized the
      association between coverage pattern and long-term patient or graft survival.
      RESULTS: Among 34,487 patients in the analysis, insurance coverage patterns
      included continuous private coverage (58%), continuous public coverage (29%),
      private to public transition (8%) and public to private transition (4%). In
      multivariable analysis of patient survival, continuous public insurance (HR 1.29,
      CI 1.22, 1.37, p < 0.001), private to public transition (HR 1.17, CI 1.07, 1.28,
      p < 0.001), and public to private transition (HR 1.14, CI 1.00, 1.29, p = 0.044),
      were associated with greater mortality hazard, compared to continuous private
      coverage. After disaggregating public coverage by source, mortality hazard was
      highest for patients transitioning from private insurance to Medicaid (HR vs.
      continuous private coverage = 1.32; 95% CI 1.14, 1.52; p < 0.001). Similar
      differences by insurance category were found for death-censored graft failure.
      CONCLUSION: Post-transplant transition to public insurance coverage is associated
      with higher risk of adverse outcomes when compared to retaining private coverage.

PMID- 29574565
TI  - Atorvastatin decreases steroid production in H295R cells and in major endocrine
      tissues of male rats.
AB  - Obesity is increasing worldwide, and since obesity is associated with
      dyslipidemia, the consumption of cholesterol-lowering pharmaceuticals has
      increased. The aim of this study was therefore to study potential endocrine
      disrupting effects of one of the world's most frequently prescribed drugs, the
      cholesterol-lowering drug, atorvastatin (ATO) in vitro using the H295R
      steroidogenesis assay and in vivo using male Sprague-Dawley rats. We analyzed all
      major steroids in the mammalian steroidogenesis using liquid chromatography
      tandem mass spectrometry (LC-MS/MS). In vitro, ATO significantly decreased all
      steroids in the H295R steroidogenesis at concentrations close to human plasma
      Cmax values, with an IC50 value for testosterone of 0.093 +/- 0.033 uM.
      Additionally, we determined steroid hormone levels in testis, adrenals, brain and
      plasma from rats after 14 days of exposure to three therapeutically relevant
      doses of ATO and observed pronounced decreasing steroid levels in particular in
      testis and adrenals but also in brain and plasma. In testis, all major
      steroidogenic enzymes were up-regulated, indicating autocrine and/or paracrine
      compensation for the decrease in steroid production by this tissue. In adrenals,
      StAR and CYP11A1 gene expression were decreased, whereas little effects were
      observed in the brain. Furthermore, we analyzed plasma LH and ACTH levels to
      investigate feedback via the PT and HPA axes. No effects were observed on LH
      levels, indicating little compensation via the PT axis. In contrast, ACTH levels
      increased during ATO exposure, indicating that the HPA axis to some extend
      compensated for the decrease in adrenal steroid production. Overall, ATO exerted
      pronounced effects on steroid production both in vitro and in vivo at
      therapeutically relevant doses. This clearly demonstrates the high potency of ATO
      to affect steroid homeostasis during therapeutic treatment. Further clinical and
      epidemiological studies should be conducted to investigate the relevance of these
      observations in patients treated with cholesterol-lowering pharmaceuticals.

PMID- 29574564
TI  - In vitro prediction of drug-induced cholestatic liver injury: a challenge for the
      toxicologist.

PMID- 29574562
TI  - Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and
      Management.
AB  - PURPOSE OF STUDY: Immune-mediated adverse drug reactions occur commonly in
      clinical practice and include mild, self-limited cutaneous eruptions, IgE
      mediated hypersensitivity, and severe cutaneous adverse drug reactions (SCAR).
      SCARs represent an uncommon but potentially life-threatening form of delayed T
      cell-mediated reaction. The spectrum of illness ranges from acute generalized
      exanthematous pustulosis (AGEP) to drug reaction with eosinophilia with systemic
      symptoms (DRESS), to the most severe form of illness, Stevens-Johnson syndrome
      (SJS) and toxic epidermal necrolysis (TEN). RECENT FINDINGS: There is emerging
      literature on the efficacy of cyclosporine in decreasing mortality in SJS/TEN.
      The purpose of our review is to discuss the typical presentations of these
      conditions, with a special focus on identifying the culprit medication. We review
      risk factors for developing SCAR, including HLA alleles strongly associated with
      drug hypersensitivity. We conclude by discussing current strategies for the
      management of these conditions.

PMID- 29574567
TI  - Two-port robotic hysterectomy: a novel approach.
AB  - The objective of the study was to demonstrate a novel technique for two-port
      robotic hysterectomy with a particular focus on the challenging portions of the
      procedure. The study is designed as a technical video, showing step-by-step a two
      port robotic hysterectomy approach (Canadian Task Force classification level
      III). IRB approval was not required for this study. The benefits of minimally
      invasive surgery for gynecological pathology have been clearly documented in
      multiple studies. Patients had fewer medical and surgical complications
      postoperatively, better cosmesis and quality of life. Most gynecological surgeons
      require 3-5 ports for the standard gynecological procedure. Even though the
      minimally invasive multiport system provides an excellent safety profile,
      multiple incisions are associated with a greater risk for morbidity including
      infection, pain, and hernia. In the past decade, various new methods have emerged
      to minimize the number of ports used in gynecological surgery. The interventions
      employed were a two-port robotic hysterectomy, using a camera port plus one
      robotic arm, with a focus on salpingectomy and cuff closure. We describe a
      transvaginal and a transabdominal approach for salpingectomy and a novel method
      for cuff closure. The transvaginal and transabdominal techniques for
      salpingectomy for two-port robotic-assisted hysterectomy provide excellent
      tension and exposure for a safe procedure without the need for an extra port. We
      also describe a transvaginal technique to place the vaginal cuff on tension
      during closure. With the necessary set of skills on a carefully chosen patient,
      two-port robotic-assisted total laparoscopic hysterectomy is a feasible
      procedure.

PMID- 29574566
TI  - Diagnostic performance of apparent diffusion coefficient parameters for glioma
      grading.
AB  - This study was to evaluate the diagnostic performance of fractional anisotropy
      (FA) and apparent diffusion coefficient (ADC) parameters derived from diffusion
      tensor imaging in the differentiation between grade II and III gliomas. The
      records of 60 patients (30 women, 30 men; mean age, 45.4 years) suspected of
      having gliomas who underwent an ADC image-guided stereotactic biopsy were
      retrospectively reviewed. The values of FA and ADC were measured, and the
      sensitivity, specificity, accuracy and area under the curve (AUC) of those
      parameters were calculated based on the receiver operating characteristic curve
      analysis. A predictive diagnostic equation was also constructed and evaluated.
      Significant differences in minimum ADC values were found in the quantitative
      analysis between the grade III and II glioma groups. The sensitivity,
      specificity, positive predictive values (PPV), negative predictive values (NPV),
      accuracy and AUC for identifying grade III and II gliomas at the optimum cut-off
      value of 0.895 * 10-3 mm2/s of minimum ADC were 81.0, 89.1, 77.3, 91.1, 86.6 and
      0.87, respectively. The predictive diagnostic equation was superior to the single
      minimum ADC indicator with a sensitivity of 90.5%, a specificity of 84.8%, a PPV
      of 73.1%, an NPV of 95.1%, and an accuracy of 86.6%, respectively. The study
      provides evidence that minimum ADC values have a superior diagnostic performance
      in differentiating grade III and II gliomas, and the predictive diagnostic
      equation may be helpful in the differentiation.

PMID- 29574568
TI  - Diffuse large B cell lymphoma (DLBCL): bilateral vanishing tibiae.

PMID- 29574569
TI  - Internal biliary stenting in liver transplantation.
AB  - PURPOSE: Internal biliary stenting (IBS) was reported to decrease biliary
      complications after liver transplantation (LT) but data in literature is scarce.
      The aim of the present study was to evaluate our experience with end-to-end
      choledoco-choledocostomy during liver transplantation with special focus on the
      influence of IBS on patient and biliary outcomes. METHODS: Between 2009 and 2013,
      175 patients underwent deceased donor LT with end-to-end choledoco-choledocostomy
      and were included in the study. Supra-papillary silastic stent was inserted in 67
      patients (38%) with small-size (< 5 mm) bile ducts (recipient or donor).
      Endoscopic retrograde cholangiopancreatography (ERCP) was scheduled for IBS
      removal, 6 months after LT. Operative outcomes and survival of patients who
      received internal stenting (IBS group) were compared with those of patients who
      did not (no-IBS group). Risk factors for biliary anastomotic complications were
      identified. RESULTS: Ten patients died (6%) and 104 (59%) experienced
      postoperative complications. Five-year patient and graft survival rates were 77
      and 74%, respectively. Biliary complications were recorded in 61 patients (35%)
      and were significantly decreased by IBS insertion (p = 0.0003). Anastomotic
      fistulas occurred in 23 patients (13%) and stenoses in 44 patients (25%). On
      multivariate analysis, high preoperative MELD scores (p = 0.02) and hepatic
      artery thrombosis (p < 0.0001) were predictors of fistula; absence of IBS was
      associated with both fistula (p = 0.014) and stricture (p = 0.003) formation.
      CONCLUSIONS: IBS insertion during LT decreases anastomotic complication.

PMID- 29574571
TI  - A bony defect of the sphenoid air sinus found in male cadaver: a case report.
AB  - The sphenoid sinus one of the posterior group of sinus, considered one of the
      most difficult sinuses due to its deep location in the skull. The interest in the
      understanding of the anatomy of the sphenoid sinus increased markedly during the
      last decades due to the development of endoscopic transsphenoidal approaches to
      the intracranial structures. The important anatomical relations of the sphenoid
      sinus make it one of the difficult and challenging structures for the surgeons.
      In this case report, we present one of the anatomical variations that was found
      during cadaveric dissection of the head. In this case we found abnormal bony
      defect in the lateral wall of the sinus, the defect closed just by the lining
      mucosa of the sinus and the dura from its intracranial side. A point may be of
      clinical importance to the related nearby structures.

PMID- 29574570
TI  - Identification and validation of genomic regions influencing kernel zinc and iron
      in maize.
AB  - KEY MESSAGE: Genome-wide association study (GWAS) on 923 maize lines and
      validation in bi-parental populations identified significant genomic regions for
      kernel-Zinc and-Iron in maize. Bio-fortification of maize with elevated Zinc (Zn)
      and Iron (Fe) holds considerable promise for alleviating under-nutrition among
      the world's poor. Bio-fortification through molecular breeding could be an
      economical strategy for developing nutritious maize, and hence in this study, we
      adopted GWAS to identify markers associated with high kernel-Zn and Fe in maize
      and subsequently validated marker-trait associations in independent bi-parental
      populations. For GWAS, we evaluated a diverse maize association mapping panel of
      923 inbred lines across three environments and detected trait associations using
      high-density Single nucleotide polymorphism (SNPs) obtained through genotyping-by
      sequencing. Phenotyping trials of the GWAS panel showed high heritability and
      moderate correlation between kernel-Zn and Fe concentrations. GWAS revealed a
      total of 46 SNPs (Zn-20 and Fe-26) significantly associated (P <= 5.03 * 10-05)
      with kernel-Zn and Fe concentrations with some of these associated SNPs located
      within previously reported QTL intervals for these traits. Three double-haploid
      (DH) populations were developed using lines identified from the panel that were
      contrasting for these micronutrients. The DH populations were phenotyped at two
      environments and were used for validating significant SNPs (P <= 1 * 10-03) based
      on single marker QTL analysis. Based on this analysis, 11 (Zn) and 11 (Fe) SNPs
      were found to have significant effect on the trait variance (P <= 0.01, R2 >=
      0.05) in at least one bi-parental population. These findings are being pursued in
      the kernel-Zn and Fe breeding program, and could hold great value in functional
      analysis and possible cloning of high-value genes for these traits in maize.

PMID- 29574572
TI  - Drug Treatment for Androgenetic Alopecia: First Italian Questionnaire Survey on
      What Dermatologists Think about Finasteride.
AB  - INTRODUCTION: Treatment with finasteride 1 mg/day represents the therapy of
      choice for androgenetic alopecia (AGA). We investigated how Italian
      dermatologists approach use of finasteride for treatment of AGA and common side
      effects reported by patients. METHODS: A tablet-based survey was conducted from
      February 2017 to January 2018 in Italy to investigating use of 1 mg/day
      finasteride in the treatment of AGA. Approximately 1153 Italian dermatologists
      were surveyed about prescription frequency, therapy duration, treatment
      practices, and side effects eventually reported. RESULTS: Dermatologists
      considered treatment with 1 mg/day finasteride to be the most efficacious
      treatment for AGA, as reflecting by its long-term (5 years) prescription. Data on
      sexual side effects from our survey are in line with previous scientific
      evidence, especially regarding loss of libido, erectile dysfunction, and problems
      with ejaculation, but also in the psychological sphere and regarding physical
      impairments such as myalgia and loss of muscle tone. CONCLUSIONS: This is the
      first preliminary observational study on how Italian dermatologists approach use
      of finasteride to treat AGA. Although side effects have been reported, especially
      in the sexual sphere, lack of alternative treatments with the same efficacy leads
      dermatologists to prescribe 1 mg/day finasteride with a tendency to prolong
      therapy in the long term. FUNDING: Giuliani S.p.A.

PMID- 29574573
TI  - More than the tip of the iceberg: association between disabilities and inability
      to attend a clinic-based post-ICU follow-up and how it may impact on health
      inequalities.

PMID- 29574574
TI  - Understanding spontaneous vs. ventilator breaths: impact and monitoring.

PMID- 29574576
TI  - Correction to: Comment on "Efficacy of a single intra-articular injection of
      ultra-high molecular weight hyaluronic acid for hip osteoarthritis: a randomized
      controlled study".
AB  - The original version of this article unfortunately contained a mistake. The first
      and last names of the authors were interchanged. The correct author names are
      given below.

PMID- 29574575
TI  - Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of
      plaque psoriasis: a review of clinical data.
AB  - Fumarates (fumaric acid esters, FAEs) are orally administered systemic agents
      used for the treatment of psoriasis and multiple sclerosis. In 1994, a
      proprietary combination of FAEs was licensed for psoriasis by the German Drug
      Administration for use within Germany. Since then, fumarates have been
      established as one of the most commonly used treatments for moderate-to-severe
      psoriasis in Germany and other countries. The licensed FAE formulation contains
      dimethyl fumarate (DMF), as well as calcium, zinc, and magnesium salts of
      monoethyl fumarate (MEF). While the clinical efficacy of this FAE mixture is well
      established, the combination of esters on which it is based, and its dosing
      regimen, was determined empirically. Since the mid-1990s, the modes of action and
      contribution of the different FAEs to their overall therapeutic effect in
      psoriasis, as well as their adverse event profile, have been investigated in more
      detail. In this article, the available clinical data for DMF are reviewed and
      compared with data for the other FAEs. The current evidence substantiates that
      DMF is the main active compound, via its metabolic transformation to monomethyl
      fumarate (MMF). A recent phase III randomized and placebo-controlled trial
      including more than 700 patients demonstrated therapeutic equivalence when
      comparing the licensed FAE combination with DMF alone, in terms of psoriasis
      clearance according to the Psoriasis Area and Severity Index (PASI) and
      Physician's Global Assessment (PGA). Thus, DMF as monotherapy for the treatment
      of psoriasis is as efficacious as in combination with MEF, making the addition of
      such fumarate derivatives unnecessary.

PMID- 29574577
TI  - Minimally invasive and percutaneous surgery of the forefoot current techniques in
      2018.
AB  - Minimally invasive and percutaneous techniques used to repair deformities of the
      forefoot have considerably developed recently. Like standard osteotomies, these
      techniques must take advantage of the mechanical advances made in the restoration
      of the foot's architecture. Instead of an endpoint, these techniques represent an
      additional tool implemented towards a rapid functional, post-operative recovery.
      This review describes the power of this surgery, details its techniques and lists
      its indications. We also report our own experience and review the recent
      literature.

PMID- 29574578
TI  - Bleaching and mortality of a photosymbiotic bioeroding sponge under future carbon
      dioxide emission scenarios.
AB  - The bioeroding sponge Cliona orientalis is photosymbiotic with dinoflagellates of
      the genus Symbiodinium and is pervasive on the Great Barrier Reef. We
      investigated how C. orientalis responded to past and future ocean conditions in a
      simulated community setting. The experiment lasted over an Austral summer under
      four carbon dioxide emission scenarios: a pre-industrial scenario (PI), a present
      day scenario (PD; control), and two future scenarios of combined ocean
      acidification and ocean warming, i.e., B1 (intermediate) and A1FI (extreme). The
      four scenarios also simulated natural variability of carbon dioxide partial
      pressure and temperature in seawater. Responses of C. orientalis generally
      remained similar between the PI and PD treatments. C. orientalis under B1
      displayed a dramatic increase in lateral tissue extension, but bleached and
      displayed reduced rates of respiration and photosynthesis. Some B1 sponge
      replicates died by the end of the experiment. Under A1FI, strong bleaching and
      subsequent mortality of all C. orientalis replicates occurred at an early stage
      of the experiment. Mortality arrested bioerosion by C. orientalis under B1 and
      A1FI. Overall, the absolute amount of calcium carbonate eroded by C. orientalis
      under B1 or A1FI was similar to that under PI or PD at the end of the experiment.
      Although bioerosion rates were raised by short-term experimental acidification in
      previous studies, our findings from the photosymbiotic C. orientalis imply that
      the effects of bioerosion on reef carbonate budgets may only be temporary if the
      bioeroders cannot survive long-term in the future oceans.

PMID- 29574579
TI  - Competition along productivity gradients: news from heathlands.
AB  - The importance of competition in low productive habitats is still debated.
      Studies which simultaneously evaluate preemption of resources and consequences
      for population dynamics are needed for a comprehensive view of competitive
      outcomes. We cultivated two emblematic species of European heathlands (Calluna
      vulgaris and Molinia caerulea) in a nursery for 2 years at two fertility levels,
      reproducing the productivity gradient found in phosphorus (P)-depleted heathlands
      in southwest France. The second year, we planted Ulex europaeus seedlings, a
      ubiquitous heathland species, under the cover of the two species to evaluate its
      ability to regenerate. Half of the seedlings were placed in tubes for exclusion
      of competitor roots. We measured the development of the competitors aboveground
      and belowground and their interception of resources (light, water, inorganic P).
      Ulex seedlings' growth and survival were also measured. Our results on resources
      interception were consistent with species distribution in heathlands. Molinia,
      which dominates rich heathlands, was the strongest competitor for light and water
      in the rich soil. Calluna, which dominates poor heathlands, increased its root
      allocation in the poor soil, decreasing water and inorganic P availability.
      However, the impact of total competition and root competition on Ulex seedlings
      decreased in the poor soil. Other mechanisms, especially decrease of water stress
      under neighbouring plant cover, appeared to have more influence on the seedlings'
      response. We found no formal contradiction between Tilman and Grime's theories.
      Root competition has a primary role in acquisition of soil resources in poor
      habitats. However, the importance of competition decreases with decreasing
      fertility.

PMID- 29574580
TI  - Simulated drought regimes reveal community resilience and hydrological thresholds
      for altered decomposition.
AB  - Future climate scenarios forecast a 10-50% decline in rainfall in Eastern
      Amazonia. Altered precipitation patterns may change important ecosystem functions
      like decomposition through either changes in physical and chemical processes or
      shifts in the activity and/or composition of species. We experimentally
      manipulated hydroperiods (length of wet:dry cycles) in a tank bromeliad ecosystem
      to examine impacts on leaf litter decomposition. Gross loss of litter mass over
      112 days was greatest in continuously submersed litter, lowest in continuously
      dry litter, and intermediate over a range of hydroperiods ranging from eight
      cycles of 7 wet:7 dry days to one cycle of 56 wet:56 dry days. The resilience of
      litter mass loss to hydroperiod length is due to a shift from biologically
      assisted decomposition (mostly microbial) at short wet:dry hydroperiods to
      physicochemical release of dissolved organic matter at longer wet:dry
      hydroperiods. Biologically assisted decomposition was maximized at wet:dry
      hydroperiods falling within the range of ambient conditions (12-22 consecutive
      dry days) but then declined under prolonged wet:dry hydroperiods (28 and 56 dry
      days. Fungal:bacterial ratios showed a similar pattern as biologically assisted
      decomposition to hydroperiod length. Our results suggest that microbial
      communities confer functional resilience to altered hydroperiod in tank bromeliad
      ecosystems. We predict a substantial decrease in biological activity relevant to
      decomposition under climate scenarios that increase consecutive dry days by 1.6-
      to 3.2-fold in our study area, whereas decreased frequency of dry periods will
      tend to increase the physicochemical component of decomposition.

PMID- 29574581
TI  - New Algorithm for the Prediction of Cardiovascular Risk in Symptomatic Adults
      with Stable Chest Pain.
AB  - PURPOSE OF REVIEW: To review the landmark studies in predicting obstructive
      coronary artery disease (CAD) in symptomatic patients with stable chest pain and
      identify better prediction tools and propose a simplified algorithm to guide the
      health care providers in identifying low risk patients to defer further testing.
      RECENT FINDINGS: There are a few risk prediction models described for stable
      chest pain patients including Diamond-Forrester (DF), Duke Clinical Score (DCS),
      CAD Consortium Basic, Clinical, and Extended models. The CAD Consortium models
      demonstrated that DF and DCS models overestimate the probability of CAD. All CAD
      Consortium models performed well in the contemporary population. PROMISE trial
      secondary data results showed that a clinical tool using readily available ten
      very low-risk pre-test variables could discriminate low-risk patients to defer
      further testing safely. In the contemporary population, CAD Consortium Basic or
      Clinical model could be used with more confidence. Our proposed simple algorithm
      would guide the physicians in selecting low risk patients who can be managed
      conservatively with deferred testing strategy. Future research is needed to
      validate our proposed algorithm to identify the low-risk patients with stable
      chest pain for whom further testing may not be warranted.

PMID- 29574583
TI  - The Broader Autism Phenotype and Visual Perception in Children.
AB  - Atypical visual perception has increasingly been described in individuals with
      autism spectrum disorders (ASD) and linked to quantitative, autism-like features
      that are present in children and adults without ASD. We investigated whether
      individual differences in visual processing skills were related to quantitative
      measures of autism traits in a pediatric sample with a range of clinical
      features. Visual processing was comprehensively characterized using the test of
      visual perceptual skills (TVPS), a standardized test of visual perception with
      seven subtests that capture a range of visual processing abilities. The TVPS
      Figure Ground (TVPS-FG) subtest requires an individual to disembed a smaller
      figure from a larger scene. TVPS-FG subtest scores were positively correlated
      with children's autism features as measured by a parental report of the Broader
      Autism Phenotype Questionnaire (BAP-Q). The correlation with BAP-Q was specific
      to the TVPS-FG subtest, as the other TVPS subtest scores were not significantly
      related to the BAP-Q. This adds to the growing body of research documenting that
      atypical visual processing is associated with the autism phenotype and highlights
      the importance of capturing quantitative traits in heterogeneous developmental
      brain disorders.

PMID- 29574582
TI  - Prion protein cleavage fragments regulate adult neural stem cell quiescence
      through redox modulation of mitochondrial fission and SOD2 expression.
AB  - Neurogenesis continues in the post-developmental brain throughout life. The
      ability to stimulate the production of new neurones requires both quiescent and
      actively proliferating pools of neural stem cells (NSCs). Actively proliferating
      NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes
      certain NSC reserves do not become depleted. The processes preserving the NSC
      quiescent pool are only just beginning to be defined. Herein, we identify a
      switch between NSC proliferation and quiescence through changing intracellular
      redox signalling. We show that N-terminal post-translational cleavage products of
      the prion protein (PrP) induce a quiescent state, halting NSC cellular growth,
      migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage
      products through reducing intracellular levels of reactive oxygen species. First,
      inhibition of redox signalling results in increased mitochondrial fission, which
      rapidly signals quiescence. Thereafter, quiescence is maintained through
      downstream increases in the expression and activity of superoxide dismutase-2
      that reduces mitochondrial superoxide. We further observe that PrP is
      predominantly cleaved in quiescent NSCs indicating a homeostatic role for this
      cascade. Our findings provide new insight into the regulation of NSC quiescence,
      which potentially could influence brain health throughout adult life.

PMID- 29574584
TI  - Phase I study of combined indomethacin and platinum-based chemotherapy to reduce
      platinum-induced fatty acids.
AB  - PURPOSE: Chemotherapy-resistance remains a major obstacle to effective anti
      cancer treatment. We previously showed that platinum analogs cause the release of
      two fatty acids. These platinum-induced fatty acids (PIFAs) induced complete
      chemoresistance in mice, whereas co-administration of a COX-1 inhibitor,
      indomethacin, prevented PIFA release and significantly enhanced chemosensitivity.
      To assess the safety of combining indomethacin with platinum-based chemotherapy,
      and to explore its efficacy and associated PIFA levels, a multi-center phase I
      trial was conducted. METHODS: The study was comprised of two arms: oxaliplatin
      plus capecitabine (CAPOX, arm I) and cisplatin plus gemcitabine, capecitabine or
      5FU (arm II) in patients for whom these regimens were indicated as standard care.
      Indomethacin was escalated from 25 to 75 mg TID, using a standard 3 * 3 design
      per arm, and was administered orally 8 days around chemo-infusion from cycle two
      onwards. PIFA levels were measured before and after treatment initiation, with
      and without indomethacin. RESULTS: Thirteen patients were enrolled, of which ten
      were evaluable for safety analyses. In arm I, no dose-limiting toxicities were
      observed, and all indomethacin dose levels were well-tolerated. Partial responses
      were observed in three patients (30%). Indomethacin lowered plasma levels of 12-S
      hydroxy-5,8,10-heptadecatrienoic acid (12-S-HHT), whereas 4,7,10,13
      hexadecatetraenoic acid (16:4(n-3)) levels were not affected. Only one patient
      was included in arm II; renal toxicity led to closure of this cohort.
      CONCLUSIONS: Combined indomethacin and CAPOX treatment is safe and reduces the
      concentrations of 12-S-HHT, which may be associated with improved
      chemosensitivity. The recommended phase II dose is 75 mg indomethacin TID given 8
      days surrounding standard dosed CAPOX.

PMID- 29574585
TI  - Direct and indirect nigrofugal projections to the nucleus reticularis pontis
      caudalis mediate in the motor execution of the acoustic startle reflex.
AB  - The acoustic startle reflex (ASR) is a short and intense defensive reaction in
      response to a loud and unexpected acoustic stimulus. In the rat, a primary
      startle pathway encompasses three serially connected central structures: the
      cochlear root neurons, the giant neurons of the nucleus reticularis pontis
      caudalis (PnC), and the spinal motoneurons. As a sensorimotor interface, the PnC
      has a central role in the ASR circuitry, especially the integration of different
      sensory stimuli and brain states into initiation of motor responses. Since the
      basal ganglia circuits control movement and action selection, we hypothesize that
      their output via the substantia nigra (SN) may interplay with the ASR primary
      circuit by providing inputs to PnC. Moreover, the pedunculopontine tegmental
      nucleus (PPTg) has been proposed as a functional and neural extension of the SN,
      so it is another goal of this study to describe possible anatomical connections
      from the PPTg to PnC. Here, we made 6-OHDA neurotoxic lesions of the SN pars
      compacta (SNc) and submitted the rats to a custom-built ASR measurement session
      to assess amplitude and latency of motor responses. We found that following
      lesion of the SNc, ASR amplitude decreased and latency increased compared to
      those values from the sham-surgery and control groups. The number of dopamine
      neurons remaining in the SNc after lesion was also estimated using a
      stereological approach, and it correlated with our behavioral results. Moreover,
      we employed neural tract-tracing techniques to highlight direct projections from
      the SN to PnC, and indirect projections through the PPTg. Finally, we also
      measured levels of excitatory amino acid neurotransmitters in the PnC following
      lesion of the SN, and found that they change following an ipsi/contralateral
      pattern. Taken together, our results identify nigrofugal efferents onto the
      primary ASR circuit that may modulate motor responses.

PMID- 29574587
TI  - Can Nuclear Imaging Techniques Predict Patient Outcome and Guide Medical
      Management in Hereditary Transthyretin Cardiac Amyloidosis?
AB  - PURPOSE OF REVIEW: Nuclear imaging recently gained a key role in the diagnosis
      and prognostic assessment of transthyretin (TTR)-related cardiac amyloidosis.
      This review aims at summarizing the state-of-the art regarding the implementation
      of nuclear imaging in the management of hereditary mutated TTR-cardiac
      amyloidosis (mTTR-CA). RECENT FINDINGS: Although cardiac uptake of bone tracers
      is acknowledged as a specific marker of TTR amyloid cardiac burden, recent
      studies validated the implementation of bone scan in the flow chart for non
      invasive diagnosis and follow-up of CA in multicenter trials. Simultaneously,
      cardiac denervation evidenced by MIBG scintigraphy proved to be a strong and
      independent prognostic marker of poor outcome in mTTR-CA. By its unique ability
      to assess both amyloid burden and cardiac denervation, nuclear imaging may prove
      useful as part of multimodality imaging tools to trigger treatment initiation and
      monitoring in patients with mTTR-CA.

PMID- 29574586
TI  - Precision Medicine in Chronic Rhinosinusitis with Nasal Polyps.
AB  - PURPOSE OF REVIEW: Chronic rhinosinusitis is a disease with high prevalence,
      significant impact on health-related quality of life (HRQoL) and it is associated
      with substantial healthcare and productivity costs. We face an urgent need to
      improve the level of disease control and achieve higher patient satisfaction and
      disease prevention. Precision medicine is increasingly recognized as the way
      forward in optimal patient care. The combination of personalized care, prevention
      of disease, prediction of success of treatment, and participation of the patient
      in the elaboration of the treatment plan is expected to guarantee the best
      possible therapeutic approach for individuals suffering from a chronic disabling
      condition. RECENT FINDINGS: This is a narrative review on the current state of
      endotypes, biomarkers, and targeted treatments in chronic inflammatory conditions
      of the nose and paranasal sinuses. Different phenotypes of rhinitis and chronic
      rhinosinusitis (CRS) have been described based on symptom severity and duration,
      atopy status, level of control, comorbidities, and presence or absence of nasal
      polyps in CRS. The underlying pathophysiological mechanisms are diverse, with
      different endotypes being recognized. Novel emerging therapies are targeting
      specific pathophysiological pathways or endotypes. This endotype-driven treatment
      approach requires careful selection of the patient population who might benefit
      from a specific treatment. This review provides a comprehensive overview of the
      current state of endotypes, biomarkers and targeted treatments in chronic
      inflammatory conditions of the nose and paranasal sinuses.

PMID- 29574588
TI  - Should Primary Prevention ICDs Still Be Placed in Patients with Non-ischemic
      Cardiomyopathy? A Review of the Evidence.
AB  - PURPOSE OF REVIEW: Recent evidence has suggested that implantable defibrillator
      (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit in
      the presence of guideline-directed medical therapy (GDMT) and cardiac
      resynchronization therapy (CRT). RECENT FINDINGS: Despite significant benefits of
      GDMT and CRT, current evidence is derived from ICD trials that rely predominantly
      on reduced left ventricular ejection fraction alone (LVEF). The majority of
      patients with sudden cardiac death (SCD) have LVEF > 30% indicating that LVEF by
      itself is an inadequate predictor of SCD. The Danish study to assess the efficacy
      of ICD in patients with non-ischemic systolic heart failure on mortality (DANISH)
      highlights the importance of better risk stratifying NICM patients for ICD
      implantation. Assessment of life expectancy, comorbidities, presence of advanced
      heart failure, etiology of NICM, and the presence of myocardial fibrosis can help
      risk stratify ICD beyond LVEF. Genetics and biomarkers can be of further
      assistance in risk stratification.

PMID- 29574589
TI  - Complete genome sequence analysis of PS2, a novel T4-like bacteriophage that
      infects Serratia marcescens clinical isolates.
AB  - In this study, we isolated and characterized a lytic phage, named vB_SmaM_PS2
      (abbreviated as PS2), which can infect Serratia marcescens clinical isolates.
      Morphologically, phage PS2 can be classified within the Myoviridae family. The
      167,276 bp double-stranded DNA genome of PS2 possesses 41.7% GC content. A total
      of 276 protein-coding genes and 4 tRNA genes were predicted in the PS2 genome. Of
      the 276 genes, 131 (47%) encoded T4-like genes, most of which are DNA replication
      and virion structural genes. Therefore, phage PS2 should be a new member of the
      T4-like Serratia phage.

PMID- 29574590
TI  - Sequence analysis and genomic organization of a new insect iflavirus, Sogatella
      furcifera honeydew virus 1.
AB  - A novel iflavirus, tentatively named "Sogatella furcifera honeydew virus 1"
      (SFHV1), discovered through transcriptome sequencing analysis of white-backed
      planthoppers (Sogatella furcifera) collected in southern China, is described
      here. The full genome of SFHV1 is 10,837 nucleotides (nt) long, including the
      polyA tail, and shares 65.5% and 64.5% genomic identity with Laodelphax
      striatellus picorna-like virus 2 and Laodelphax striatella honeydew virus 1,
      respectively. On the basis of the phylogenetic analysis of the complete genomic
      sequence and the deduced RdRp amino acid sequence of SFHV1 with other
      iflaviruses, we suggest that it is a member of a new species in the genus
      Iflavirus, family Iflaviridae.

PMID- 29574591
TI  - Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with
      allocortical/hippocampal microinfarcts and cognitive decline.
AB  - Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid beta
      protein (Abeta) in the wall of cerebral and leptomeningeal blood vessels and is
      related to Alzheimer's disease (AD). Capillary Abeta deposition is observed in a
      subset of CAA cases and represents a distinct type of CAA named capillary CAA or
      CAA type 1. This type of CAA is strongly associated with the presence of the
      apolipoprotein E epsilon4 allele. CAA type 1-associated AD cases often exhibit a
      more severe Abeta plaque pathology but less widespread neurofibrillary tangle
      (NFT) pathology. The objective of this study was to analyze whether capillary CAA
      and its effects on cerebral blood flow have an impact on dementia. To address
      this objective, we performed neuropathological evaluation of 284 autopsy cases of
      demented and non-demented individuals. We assessed the presence of CAA and its
      subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA
      severity were associated with allocortical microinfarcts, comprising the CA1
      region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA
      severity were, thereby, associated with cognitive decline. In conclusion,
      allocortical microinfarcts, CAA severity, and the capillary type of CAA were
      associated with one another and with the development of cognitive decline. Thus,
      AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not
      only due to AD-related Abeta plaque and NFT pathology but also due to hippocampal
      microinfarcts that are associated with CAA type 1 and CAA severity, and that
      damage a brain region important for memory function.

PMID- 29574593
TI  - Longitudinal brain activation changes related to electrophysiological findings in
      patients with cervical spondylotic myelopathy before and after spinal cord
      decompression: an fMRI study.
AB  - BACKGROUND: Cervical spondylotic myelopathy (CSM) is the most common cause of
      spinal cord dysfunction, potentially leading to severe disability. Abnormal
      cervical spine magnetic resonance imaging (MRI) and motor evoked potentials
      (MEPs) are independent predictors of disease progression. Abnormal MRI is
      accompanied by various activation changes in functional brain MRI (fMRI), whereas
      preoperative and postoperative fMRI adaptations associated with abnormal
      preoperative MEP remain unknown. METHODS: Twenty patients (9 males, average age
      56.6) with evidence of spinal cord compression on MRI and clinical signs of mild
      CSM were included. Participants were classified according to their preoperative
      MEP and underwent three brain fMRI examinations: before surgery, 6, and 12 months
      after surgery while performing repeated extension-flexion of each wrist. RESULTS:
      Functional MRI activation was compared between two subsets of patients, with
      normal and clearly abnormal MEP (right wrist: 8 vs. 8; left wrist: 7 vs. 9). At
      baseline, abnormal MEPs were associated with hyperactivation in the cerebellum.
      At the first follow-up, further hyperactivations emerged in the contralateral
      sensorimotor cortices and persisted for 1 year. In normal baseline MEP,
      activation mostly decreased in the ipsilateral sensorimotor cortex
      postoperatively. The ipsilateral sensorimotor activation after 1-year follow-up
      correlated with baseline MEP. CONCLUSIONS: Abnormal corticospinal MEP findings in
      cervical spondylotic myelopathy were associated with differences in brain
      activation, which further increased after spinal cord decompression and did not
      resolve within 12-month follow-up. In summary, surgery may come too late for
      those patients with abnormal MEP to recover completely despite their mild
      clinical signs and symptoms.

PMID- 29574592
TI  - Ectopic Expression of Rice PYL3 Enhances Cold and Drought Tolerance in
      Arabidopsis thaliana.
AB  - Abscisic acid (ABA) plays an important role in plant development and adaptation
      to abiotic stresses. The pyrabactin resistance-like (PYL) gene family has been
      characterized as intracellular ABA receptors in Arabidopsis. We describe here the
      functional characterization of PYL3 ABA receptor from a drought-tolerant rice
      landrace Nagina 22 (N22). The induced expression level of the PYL3 transcript was
      observed in the N22 under different stress treatments, including cold, drought,
      high temperature, salt and ABA. In contrast, the expression of PYL3 was down
      regulated in drought-susceptible rice cv. IR64 in response to above stresses. C
      terminal GFP translational fusion of OsPYL3 was localized to both cytosol and
      nucleus explaining in part functional conservation of PYL protein as ABA
      receptor. Arabidopsis transgenic lines overexpressing OsPYL3 were hypersensitive
      to ABA suggesting ABA signaling pathway-dependent molecular response of the
      OsPYL3. Further, constitutive overexpression of OsPYL3 in Arabidopsis led to
      improved cold and drought stress tolerance. Thus, OsPYL3 identified in this study
      could be a good candidate for genetic improvement of cold and drought stress
      tolerance of rice and other crop plants.

PMID- 29574594
TI  - Endomyocardial biopsy at the time of ablation or device implantation.
AB  - PURPOSE: Cardiomyopathies frequently lead to conduction system disease and/or
      arrhythmias necessitating device therapy, catheter ablation, or both.
      Endomyocardial biopsy (EMB) is avoided with recent right ventricle (RV) lead
      implants and optimal timing is uncertain. We determined outcomes of EMB at the
      time of ablation or device implantation procedures. METHODS: We retrospectively
      analyzed patients undergoing EMB during their electrophysiological procedure
      between January 2014 and July 2016. EMB was obtained using cephalic/subclavian
      access prior to device implants or femoral venous/arterial access after ablation
      procedures. Sites of electrogram (EGM) abnormality and/or scar on imaging were
      targeted when possible. RESULTS: Twenty-five patients (23 male, 59.7 +/- 15.1
      years) were included. Sixteen had reduced ejection fraction. EMB was performed
      during device implants in 9, during ablation in 13, and during combined
      procedures in 3 patients. RV and left ventricle (LV) EMB were obtained in 19 and
      6 patients, respectively. 3.9 +/- 1.8 samples/patient (median 4) were obtained.
      EMB yielded a diagnosis in 7 (28%, all RV) patients (4 cardiac implantable
      electronic device implantation, 2 ablation, and 1 both): cardiac amyloid in 4,
      lymphocytic myocarditis in 2, and cardiac sarcoid in 1. All 7 patients had
      imaging or voltage abnormalities in the chamber biopsied. Abnormal but non
      diagnostic findings, most commonly fibrotic change, were found in 14 patients. At
      mean follow-up of 1.1 +/- 0.9 years, 5 other patients received a clinical
      diagnosis (3 cardiac sarcoid, 1 arrhythmogenic cardiomyopathy, and 1 Brugada
      syndrome/arrhythmogenic cardiomyopathy overlap syndrome). Two patients developed
      minor device pocket hematomas and one developed pericardial effusion (underwent
      concomitant epicardial mapping and ablation for VT). CONCLUSIONS: RV or LV EMB
      can be performed safely during EP procedures and can assist with diagnosis,
      influencing management. EGM-guided EMB in patients presenting with scar-related
      VT was low yield for specific pathologies.

PMID- 29574595
TI  - High rate of persistent iatrogenic atrial septal defect after single transseptal
      puncture for cryoballoon pulmonary vein isolation.
AB  - PURPOSE: Congenital atrial septal defect (ASD) is associated with increased
      morbidity, whereas little is known about the rate of spontaneous closure,
      associated clinical and echocardiographic parameters, or complications of
      iatrogenic atrial septal defect (iASD) beyond 1 year of follow-up. Persistent
      iASD after transseptal puncture for PVI has been described in up to 38% of small
      cohorts of patients in short-term follow-up after transseptal puncture. We sought
      to investigate the course of iASD after single transseptal puncture for first
      pulmonary vein isolation (PVI) with cryoballoon, along with possible risk factors
      for persistent iASD. METHODS: After a first PVI with cryoballoon, 102 patients
      (64 +/- 10 years, 64% male) underwent long-term clinical follow-up and
      comprehensive transthoracic and transesophageal echocardiographic study. RESULTS:
      Prevalence of iASD after PVI was 37% after 2.9 (1.6-4.9) years. No clinical
      complications or deterioration of echocardiographic parameters were associated
      with iASD. Lower left atrial appendage flow velocity was associated with higher
      risk of persistence of iASD (3.5% for every 1 cm/s decrease, p = 0.002).
      CONCLUSIONS: Despite a high rate of iASD after cryoballoon PVI in long-term
      follow-up, this was not associated with increased clinical complications. Lower
      LAA velocity was associated with higher risk of persistent iASD. Repeated routine
      echocardiographic follow-up may not be necessary in these patients.

PMID- 29574596
TI  - Characterization and modelling of looming-sensitive neurons in the crab
      Neohelice.
AB  - Looming-sensitive neurons (LSNs) are motion-sensitive neurons tuned for detecting
      imminent collision. Their main characteristic is the selectivity to looming (a 2D
      representation of an object approach), rather than to receding stimuli. We
      studied a set of LSNs by performing surface extracellular recordings in the optic
      nerve of Neohelice granulata crabs, and characterized their response against
      computer-generated visual stimuli with different combinations of moving edges,
      highlighting different components of the optical flow. In addition to their
      selectivity to looming stimuli, we characterized other properties of these
      neurons, such as low directionality; reduced response to sustained excitement;
      and an inhibition phenomenon in response to visual stimuli with dense optical
      flow of expansion, contraction, and translation. To analyze the spatio-temporal
      processing of these LSNs, we proposed a biologically plausible computational
      model which was inspired by previous computational models of the locust lobula
      giant motion detector (LGMD) neuron. The videos seen by the animal during
      electrophysiological experiments were applied as an input to the model which
      produced a satisfactory fit to the measured responses, suggesting that the
      computation performed by LSNs in a decapod crustacean appears to be based on
      similar physiological processing previously described for the LGMD in insects.

PMID- 29574597
TI  - Reducing post-tonsillectomy haemorrhage rates through a quality improvement
      project using a Swedish National quality register: a case study.
AB  - PURPOSE: Tonsillectomy (TE) is one of the most frequently performed ENT surgical
      procedures. Post-tonsillectomy haemorrhage (PTH) is a potentially life
      threatening complication of TE. The National Tonsil Surgery Register in Sweden
      (NTSRS) has revealed wide variations in PTH rates among Swedish ENT centres. In
      2013, the steering committee of the NTSRS, therefore, initiated a quality
      improvement project (QIP) to decrease the PTH incidence. The aim of the present
      study was to describe and evaluate the multicentre QIP initiated to decrease PTH
      rates. METHODS: Six ENT centres, all with PTH rates above the Swedish average,
      participated in the 7-month quality improvement project. Each centre developed
      improvement plans describing the intended changes in clinical practice. The
      project's primary outcome variable was the PTH rate. Process indicators, such as
      surgical technique, were also documented. Data from the QIP centres were compared
      with a control group of 15 surgical centres in Sweden with similarly high PTH
      rates. Data from both groups for the 12 months prior to the start of the QIP were
      compared with data for the 12 months after the QIP. RESULTS: The QIP centres
      reduced the PTH rate from 12.7 to 7.1% from pre-QIP to follow-up; in the control
      group, the PTH rate remained unchanged. The QIP centres also exhibited positive
      changes in related key process indicators, i.e., increasing the use of cold
      techniques for dissection and haemostasis. CONCLUSIONS: The rates of PTH can be
      reduced with a QIP. A national quality register can be used not only to identify
      areas for improvement but also to evaluate the impact of subsequent improvement
      efforts and thereby guide professional development and enhance patient outcomes.

PMID- 29574598
TI  - Synchronized roles of pannexin and connexin in nasal mucosal epithelia.
AB  - BACKGROUND: Nasal mucosal epithelial cells express connexins, the prototypical
      gap junction proteins, and pannexins, a new family of channel proteins homologous
      to the invertebrate gap junction proteins. The physiological and
      pathophysiological roles of these transmembrane proteins in nasal mucosa are
      largely still unknown. PURPOSE: Pannexins participate in ATP release into the
      extracellular space in various tissues, and ATP plays important roles in
      mucociliary clearance, especially by regulating ciliary beat activity. Therefore,
      we focused on the functional relationship between connexins, pannexin-1, ATP
      release, and mucociliary clearance in nasal epithelia. RESULTS AND CONCLUSIONS:
      Connexins participate in the generation of intercellular calcium waves, in which
      calcium-mediated signaling responses spread to contiguous cells through the gap
      junction formed by connexins to transmit calcium signaling throughout the airway
      epithelium. Pannexins in the nasal mucosa may contribute to not only ciliary beat
      modulation via ATP release, but also regulation of mucus blanket components via
      H2O efflux. The synchronized roles of pannexin and connexin may provide a new
      insight into effective mucociliary clearance systems in nasal mucosa.

PMID- 29574599
TI  - Pharyngeal fistulas after total laryngectomy with and without tracheostoma plasty
      according to Herrmann.
AB  - PURPOSE: Pharyngeal fistula (PF) is one of the most common complications after
      total laryngectomy (TL). The tracheostoma plasty technique according to Herrmann
      (TPH) represents an alternative surgical technique to shape the tracheostoma. The
      aim of this study was to determine whether the performance of a TPH affects the
      incidence of PF after TL. A secondary aim was to identify potential risk factors
      for the development of PF with regard to TPH. METHODS: Retrospective evaluation
      of records of 151 consecutive patients at two tertiary care centers with regard
      to the occurrence and risk factors of PF after TL with and without TPH. RESULTS:
      60 patients with TPH and 91 patients without TPH contributed to the results. The
      overall incidence of PF was 21.2% (32 out of 151). 23.3% (14 out of 60) of
      patients with TPH and 19.8% (18 of 91) of patients without TPH developed a PF (p
      = 0.91). Binary logistic regression analysis revealed significant influence of
      salvage surgery on the risk to develop PF (odds ratio = 2.9; 95% CI 1.16-7.23; p
      = 0.026). The occurrence of PF was not significantly influenced by any other
      investigated factors including performance of TPH. CONCLUSIONS: Performance of
      TPH after TL does not increase the incidence of PF. Thus, TPH can be considered
      as a safe alternative surgical technique for the shaping of the tracheostoma
      following TL.

PMID- 29574600
TI  - Rates and predictors of futile recanalization in patients undergoing endovascular
      treatment in a multicenter clinical trial.
AB  - PURPOSE: The phenomenon of futile recanalization, defined as lack of clinical
      benefit despite angiographic recanalization, is an important limitation of
      endovascular treatment for acute ischemic stroke. We aim to characterize the
      occurrence and predictors of futile recanalization in the endovascular arm of the
      Interventional Management of Stroke (IMS) III trial. METHODS: Patients with near
      complete or complete recanalization (TICI grades 2b and 3) were divided according
      to functional outcome at 3 months into "meaningful recanalization," defined as
      mRS score 0-2, and "futile recanalization," mRS score 3-6. Multivariate analysis
      was performed to identify predictors of futile recanalization. RESULTS: Futile
      recanalization was observed in 61 (47%) of 130. Compared to meaningful
      recanalization group, the futile recanalization group had higher proportion of
      women (62.3 vs. 43.5%; p = 0.032), higher incidence of diabetes mellitus (29.5
      vs. 8.7%; p = 0.004) and coronary artery disease (27.9 vs. 13%; p = 0.05), higher
      baseline National Institutes of Health Stroke Scale (NIHSS) scores (median
      [range] 19 [11-31] vs. 15 [8-26], p < 0.001), higher baseline serum glucose (7.6
      +/- 2.6 vs. 6.7 +/- 1.7 mmol/L; p = 0.039), and longer onset-to-start of
      endovascular treatment time (265.8 +/- 48.3 vs. 239.2 +/- 47.7 min; p = 0.007).
      In multivariate analysis, NIHSS (OR 1.3; 95% CI 1.1-1.4), female gender (OR 3.0;
      95% CI 1.1-8.2), and onset-to-start of endovascular treatment time (OR 1.2; 95%
      CI 1.1-1.3) were independent predictors of futile recanalization. CONCLUSION: In
      IMS III, futile recanalization was common. Delay in endovascular treatment is the
      only modifiable risk factor. Additional strategies for non-modifiable risk
      factors-female gender and high NIHSS-need to be identified.

PMID- 29574601
TI  - Headache and Its Management in Patients With Multiple Sclerosis.
AB  - PURPOSE OF REVIEW: The purpose of this review was to discuss the prevalence,
      impact, pathophysiology, and treatment of headaches (H/As) in patients with
      multiple sclerosis (MS). RECENT FINDINGS: Headaches and multiple sclerosis are
      more common in women than in men with the ratio of female to male being 3:1. It
      is not entirely clear if there is a correlation or an incidental comorbidity of
      two neurological conditions. A review of the literature shows a variable
      prevalence of H/As in MS patients. Using the International Classification of
      Headache Disorders (ICHD) criteria, the primary type of H/As, especially
      migraine, is the most common type seen in patients with MS. One of the theories
      of the pathophysiologic mechanisms of migraine in MS patients is inflammation
      leading to demyelinating lesions in the pain-producing centers in the midbrain.
      Secondary H/As due to MS medications such as interferons are also frequently
      present. H/As can be a cause for significant comorbidity in patients with MS. The
      treatment of H/As in patients with MS should be addressed in the same fashion as
      in the non-MS population, which is a combination of pharmacological and non
      pharmacological methods. Preventive medicines for the H/As should be carefully
      selected because of their side effect profiles. Acute attacks of migraines can be
      treated with medications such as triptans. Patients with MS who have migraine
      H/As should be educated about the phenomenon of overuse H/As, keeping headache
      journals, avoiding stress, and monitoring sleeping habits. The presence of
      depression in patients with MS and migraine affects quality of life (QOL) and
      should also be addressed for better outcomes.

PMID- 29574602
TI  - Enhanced lincomycin production by co-overexpression of metK1 and metK2 in
      Streptomyces lincolnensis.
AB  - Streptomyces lincolnensis is generally utilized for the production of lincomycin
      A (Lin-A), a clinically useful antibiotic to treat Gram-positive bacterial
      infections. Three methylation steps, catalyzed by three different S
      adenosylmethionine (SAM)-dependent methyltransferases, are required in the
      biosynthesis of Lin-A, and thus highlight the significance of methyl group supply
      in lincomycin production. In this study, we demonstrate that externally
      supplemented SAM cannot be taken in by cells and therefore does not enhance Lin-A
      production. Furthermore, bioinformatics and in vitro enzymatic assays revealed
      there exist two SAM synthetase homologs, MetK1 (SLCG_1651) and MetK2 (SLCG_3830)
      in S. lincolnensis that could convert L-methionine into SAM in the presence of
      ATP. Even though we attempted to inactivate metK1 and metK2, only metK2 was
      deleted in S. lincolnensis LCGL, named as DeltametK2. Following a reduction of
      the intracellular SAM concentration, DeltametK2 mutant exhibited a significant
      decrease of Lin-A in comparison to its parental strain. Individual overexpression
      of metK1 or metK2 in S. lincolnensis LCGL either elevated the amount of
      intracellular SAM, concomitant with 15% and 22% increase in Lin-A production,
      respectively. qRT-PCR assays showed that overexpression of either metK1 or metK2
      increased the transcription of lincomycin biosynthetic genes lmbA and lmbR, and
      regulatory gene lmbU, indicating SAM may also function as a transcriptional
      activator. When metK1 and metK2 were co-expressed, Lin-A production was increased
      by 27% in LCGL, while by 17% in a high-yield strain LA219X.

PMID- 29574603
TI  - Nationwide survey of therapy-related leukemia in childhood in Japan.
AB  - Therapy-related leukemia (t-leukemia) is associated with dismal prognosis.
      Published pediatric t-leukemia data are somewhat outdated and may not reflect
      recent advances in treatment. We report a retrospective nationwide survey of
      patients diagnosed between 2000 and 2013 in Japan. We identified 43 patients with
      pediatric t-leukemia; 33 had t-acute myeloid leukemia (t-AML), eight had t-acute
      lymphoblastic leukemia (t-ALL) and two had t-acute undifferentiated leukemia.
      Median age at onset and latency were 12 years and 3.8 years, respectively,
      consistent with previous reports. Of t-AML patients, 63.6% harbored topoisomerase
      II inhibitor (topo II)-related genetic abnormalities, while only 12.5% of t-ALL
      patients had such alterations, suggesting that topo II is not key to t-ALL
      leukemogenesis. The 7-year overall survival (OS) for all 43 patients was 39.2 +/-
      11.6%. The 5-year OS was 50 +/- 20.4% in t-ALL, and 55.2 +/- 11.0% in t-AML.
      Allogeneic hematopoietic cell transplantation (allo-HCT) was associated with
      superior 5-year OS (HCT(+) vs. HCT(-), 78.8 vs. 12.1%; p < 0.001), and 26 of 32
      patients received allo-HCT in complete remission (CR). Only allo-HCT was
      associated with superior OS on multivariate analysis (HR 0.003, 95% CI 0.0001
      0.098; p < 0.001). These findings suggest that allo-HCT in CR improves pediatric
      t-leukemia outcomes.

PMID- 29574604
TI  - Evolution of Melanoma Antigen-A11 (MAGEA11) During Primate Phylogeny.
AB  - Melanoma antigen-A11 (MAGE-A11) is an X-linked and primate-specific steroid
      hormone receptor transcriptional coregulator and proto-oncogenic protein whose
      increased expression promotes the growth of prostate cancer. The MAGEA11 gene is
      expressed at low levels in normal human testis, ovary, and endometrium, and at
      highest levels in castration-resistant prostate cancer. Annotated genome
      predictions throughout the surviving primate lineage show that MAGEA11 acquired
      three 5' coding exons unique within the MAGEA subfamily during the evolution of
      New World monkeys (NWM), Old World monkeys (OWM), and apes. MAGE-A11 in all
      primates has a conserved FXXIF coactivator-binding motif that suggests
      interaction with p160 coactivators contributed to its early evolution as a
      transcriptional coregulator. An ancestral form of MAGE-A11 in the more distantly
      related lemur has significant amino acid sequence identity with human MAGE-A11,
      but lacks coregulator activity based on the absence of the three 5' coding exons
      that include a nuclear localization signal (NLS). NWM MAGE-A11 has greater amino
      acid sequence identity than lemur to human MAGE-A11, but inframe premature stop
      codons suggest that MAGEA11 is a pseudogene in NWM. MAGE-A11 in OWM and apes has
      nearly identical 5' coding exon amino acid sequence and conserved interaction
      sites for p300 acetyltransferase and cyclin A. We conclude that the evolution of
      MAGEA11 within the lineage leading to OWM and apes resulted in steroid hormone
      receptor transcriptional coregulator activity through the acquisition of three 5'
      coding exons that include a NLS sequence and nonsynonymous substitutions required
      to interact with cell cycle regulatory proteins and transcription factors.

PMID- 29574605
TI  - Climate Change and the Impact on Respiratory and Allergic Disease: 2018.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review allergic respiratory
      disease related to indoor and outdoor exposures and to examine the impact of
      known and projected changes in climate. The global burden of disease directly
      attributed to climate change is very difficult to measure and becomes more
      challenging when the capacity of humans to adapt to these changes is taken into
      consideration. Allergic respiratory disease, such as asthma, is quite
      heterogenous, though closely associated with environmental and consequently
      immunologic interaction. Where is the tipping point? RECENT FINDINGS: Our climate
      has been measurably changing for the past 100 years. It may indeed be the most
      significant health threat of the twenty-first century, and consequently tackling
      climate change may be the greatest health opportunity. The impacts of climate
      change on human health are varied and coming more into focus. Direct effects,
      such as heatwaves, severe weather, drought, and flooding, are apparent and
      frequently in the news. Indirect or secondary effects, such as changes in
      ecosystems and the impact on health, are less obvious. It is these changes in
      ecosystems that may have the greatest impact on allergic and respiratory
      diseases. This review will explore some ways that climate change, current and
      predicted, influences respiratory disease. Discussion will focus on changing
      pollen patterns, damp buildings with increased mold exposure, air pollution, and
      heat stress.

PMID- 29574607
TI  - The effect of bovine colostrum supplementation on intestinal injury and
      circulating intestinal bacterial DNA following exercise in the heat.
AB  - PURPOSE: Exercise-induced changes in intestinal permeability are exacerbated in
      the heat. The aim of this study was to determine the effect of 14 days of bovine
      colostrum (Col) supplementation on intestinal cell damage (plasma intestinal
      fatty acid-binding protein, I-FABP) and bacterial translocation (plasma bacterial
      DNA) following exercise in the heat. METHODS: In a double-blind, placebo
      controlled, crossover design, 12 males completed two experimental arms (14 days
      of 20 g/day supplementation with Col or placebo, Plac) consisting of 60 min
      treadmill running at 70% maximal aerobic capacity (30  degrees C, 60% relative
      humidity). Blood samples were collected pre-exercise (Pre-Ex), post-exercise
      (Post-Ex) and 1 h post-exercise (1 h Post-Ex) to determine plasma I-FABP
      concentration, and bacterial DNA (for an abundant gut species, Bacteroides).
      RESULTS: Two-way repeated measures ANOVA revealed an arm * time interaction for I
      FABP (P = 0.005, with greater Post-Ex increase in Plac than Col, P = 0.01: Plac
      407 +/- 194% of Pre-Ex vs Col, 311 +/- 134%) and 1 h Post-Ex (P = 0.036: Plac 265
      +/- 80% of Pre-Ex vs Col, 229 +/- 56%). There was no interaction (P = 0.904) but
      there was a main effect of arm (P = 0.046) for plasma Bacteroides/total bacterial
      DNA, with lower overall levels evident in Col. CONCLUSION: This is the first
      investigation to demonstrate that Col can be effective at reducing intestinal
      injury following exercise in the heat, but exercise responses (temporal pattern)
      of bacterial DNA were not influenced by Col (although overall levels may be
      lower).

PMID- 29574606
TI  - Effectiveness of Psycho-Physiological Portable Devices to Analyse Effect of
      Ergogenic Aids in Military Population.
AB  - Caffeine is one of the ergogenic substances most used by warfighters in current
      operation areas, but the effect on the organic response and operational performed
      is already poor knowledge. This research aimed to study the acute effect of 400
      mg of caffeine monohydrate on the psycho-physiological response and rifle
      marksmanship of warfighters during a close quarter combat simulation. We analysed
      parameter of heart rate, blood lactate, cortical arousal, state anxiety and
      marksmanship of 20 Spanish Army veteran warfighters before and after a close
      quarter combat simulation in a double-blind procedure, also a correlation
      analysis was conducted between all the study variables. Marksmanship of
      warfighters did not improve with the caffeine ingestion, but it produced an
      increase in blood lactate concentration (caffeine: 1.9 +/- 0.5 vs. 9.2 +/- 1.1
      mmol.l-1; placebo: 1.8 +/- 0.7 vs. 6.9 +/- 2.2 mmol.l-1), cortical arousal (% of
      change: caffeine: 2.51; placebo: -1.96) and heart rate (caffeine: 80.0 +/- 7.2
      vs. 172.9 +/- 28.2 bpm; placebo: 79.3 +/- 6.4 vs. 154.0 +/- 26.8 bpm). In
      addition, higher heart rate values correlated negatively with marksmanship in
      close quarter combat. We concluded that caffeine intake did not improve the
      warfighters rifle marksmanship in close quarter combat possibly due to the
      increase in the physiological response.

PMID- 29574608
TI  - Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a
      case-control study.
AB  - PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a complex disease,
      resulting from a variety of genetic and environmental factors. The aim of this
      case-control study was to evaluate the effect of selected genetic polymorphisms,
      nutrition aspects and their interaction on the risk of NAFLD. METHODS: The sample
      consisted of 134 patients with NAFLD and 217 controls. Disease was diagnosed by
      liver ultrasound and volunteers were clinically and nutritionally assessed. Food
      groups were extracted from a 172 food-item FFQ questionnaire. Three genetic
      polymorphisms were assessed: PNPLA3 rs738409, TM6SF2 rs58542926 and GCKR
      rs780094. RESULTS: We replicated the effect of previously reported risk factors
      for NAFLD, such as elevated liver enzymes, obesity and metabolic syndrome. Food
      groups rich in simple sugars, fat and especially saturated fat were positively
      associated with NAFLD risk, whereas food groups rich in polyunsaturated fatty
      acids were reversely associated with the possibility of developing the disease (p
      < 0.05). Only the PNPLA3 genetic variant was statistically significantly
      associated with the disease (padditive = 0.015). However, it was found that a one
      portion increase in fish intake increased the risk of NAFLD in carriers of the
      risk allele of TM6SF2 rs58542926 polymorphism compared to non-carriers, after
      adjusting for age, gender, energy intake, pack-years, PAL, TM6SF2 genotype and
      fish consumption (ORdominant = 1.503, 95% CI 1.094-2.064). CONCLUSIONS: Fish
      intake exerts an additive effect on NAFLD risk for carriers of the TM6SF2
      polymorphism. This novel finding provides further rationale on the need for
      personalized nutritional advice, based on the genetic background of NAFLD
      patients.

PMID- 29574609
TI  - Outcome of immature oocytes collection of 119 cancer patients during ovarian
      tissue harvesting for fertility preservation.
AB  - PURPOSE: Few clinical options for fertility preservation are available to females
      with cancer, and data about clinical outcomes is limited. Potential supplementary
      approaches to fertility preservation include retrieval of immature oocytes
      followed by in vitro maturation (IVM) and storage. The aim of this study was to
      evaluate post-thawing outcomes of immature oocytes collected both by transvaginal
      aspiration and from excised ovarian tissue. METHODS: We conducted a retrospective
      cohort study of patients treated in a single tertiary center. We reviewed the
      records of 119 cancer patients who underwent ovarian tissue cryopreservation and
      immature oocyte harvesting for fertility preservation. All embryos and oocytes
      that were frozen and thawed were included in the study. Post-thawing outcomes
      were evaluated. RESULTS: Thirty-five stored embryos from eight patients were
      thawed. Twenty-nine embryos survived (82% survival rate) and were transferred.
      Six oocytes were thawed, two oocytes survived, and no oocytes were fertilized.
      Only one PCOS patient became pregnant, resulting in the normal delivery of a
      healthy baby. CONCLUSIONS: Although a relatively high number of mature oocytes
      and embryos can be stored with the combined procedure, the limited rate of
      pregnancies represents a poor reproductive outcome. Therefore, this approach
      should be reserved for special groups with limited options.

PMID- 29574610
TI  - Platelet response to direct thrombin inhibitor or fondaparinux treatment in
      patients with suspected heparin-induced thrombocytopenia.
AB  - Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be
      problematic. A prompt platelet rise following treatment has been proposed as a
      "post-test" criterion for diagnosis. However, the platelet response following
      discontinuation of heparin and initiation of a recommended alternative
      anticoagulant remains largely undefined and unstudied. This study aimed to
      characterize platelet response to initial treatment in patients with a low,
      intermediate, or high likelihood of having HIT. This was a multicenter
      retrospective cohort study. Patients were over 18 years in age, underwent
      serologic testing for HIT, and received alternative anticoagulation treatment for
      HIT. Classification of each patient's likelihood of having HIT was based on an
      empiric, pre-hoc combination of the 4T score and serology results. The primary
      outcome for this study was a platelet count response after initiation of direct
      thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were
      analyzed. The sensitivity and specificity of having an immediate platelet rise of
      at least 10,000/uL by day 2 after starting treatment among high-likelihood for
      HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76),
      respectively. The negative predictive value of no platelet rise was 75.5% (95% CI
      0.61-0.86). A prompt platelet count rise may be appropriate to consider along
      with other known criteria for the clinical diagnosis of HIT. The rise should be
      immediate following discontinuation of heparin and initiation of recommended
      treatment, with an upward rise within 48 h.

PMID- 29574611
TI  - Betting on Life: Associations Between Significant Life Events and Gambling
      Trajectories Among Gamblers with the Intent to Quit.
AB  - Considerable evidence has suggested that problem gambling may be transitory and
      episodic, with gamblers routinely moving in and out of clinical thresholds.
      Findings in qualitative and quantitative studies have converged on identifying
      preliminary evidence for the role of life events as motivators and contributing
      factors for gambling changes over time. The aim of this study was to conduct an
      exploratory analysis of the relationship between life events, their respective
      experience as positive or negative, and gambling trajectories among problem
      gamblers intending to quit. Life event occurrence and ratings as positive or
      negative, and changes in gambling severity were analyzed over a 12-month period
      for 204 adult problem gamblers intending to reduce or quit their gambling.
      Overall, mixed effects models revealed several relationships between life events
      and both the magnitude and direction of gambling change over time. In particular,
      gamblers who experienced a greater number of positive events or specific events
      such as legal events, the adoption/loss of a child, or negative changes to their
      social relationships, finances, work environments or social/health activities
      were more likely to exhibit greater gambling reductions over time. Conversely,
      gamblers who experienced a greater number of negative events, such as family
      bereavement, the dissolution of a marriage, or negative changes to their
      residence exhibited smaller gambling reductions or increases in gambling
      severity. Possible mechanisms which may explain the findings and the importance
      of examining the subjective experience of life events are discussed.
      Recommendations for future studies examining associations between life events and
      gambling trajectories are provided.

PMID- 29574612
TI  - Effect of BMI on allograft function and survival in pediatric renal transplant
      recipients.
AB  - OBJECTIVE: To determine whether pre-transplant body mass index (BMI) affects
      renal allograft function and survival in pediatric renal transplant recipients.
      STUDY DESIGN: This is a retrospective cohort study using the Organ Procurement
      and Transplantation Network data from 2000 to 2013 to compare time to total
      allograft loss (allograft failure or death), prevalence of delayed graft
      function, prevalence of acute rejection, and estimated glomerular filtration rate
      (eGFR) post-transplant in pediatric renal transplant recipients categorized by
      BMI z-score. RESULTS: A total of 8804 kidney transplant recipients met our
      inclusion criteria, and of those, 6% were underweight, 14% were overweight, and
      17% were obese pre-transplant. The adjusted hazard ratio (HR) for allograft
      failure was significantly higher for obese recipients compared to normal weight
      recipients (HR 1.25, 95% CI 1.1, 1.42); for every 1 point increase in BMI z
      score, there was a 7% increased hazard of allograft failure (HR 1.07; 95% CI 1.03
      1.1, p < 0.001). The prevalence of delayed graft function and acute rejection
      increased with higher BMI z-score category; however, this difference did not
      reach statistical significance. eGFR at 1 and 5 years post-transplant decreased
      with higher BMI z-score although it was only statistically significant at 1 year.
      CONCLUSIONS: Obesity is prevalent in pediatric renal transplant recipients, and
      obese, but not overweight or underweight, pediatric renal transplant recipients
      have an increased risk of allograft failure. Implementation of effective obesity
      interventions in pediatric renal transplant recipients is of critical importance
      to improve longevity of the renal allograft.

PMID- 29574613
TI  - Expanding tryptophan-containing cyclodipeptide synthase spectrum by
      identification of nine members from Streptomyces strains.
AB  - Cyclodipeptide synthases (CDPSs) comprise normally 200-300 amino acid residues
      and are mainly found in bacteria. They hijack aminoacyl-tRNAs from the ribosomal
      machinery for cyclodipeptide formation. In this study, nine new CDPS genes from
      eight Streptomyces strains were cloned into pET28a vector and expressed in
      Escherichia coli. Structural elucidation of the isolated products led to the
      identification of one cyclo-L-Trp-L-Leu, two cyclo-L-Trp-L-Pro, and three cyclo-L
      Trp-L-Trp synthases. Other three CDPSs produce cyclo-L-Trp-L-Ala or cyclo-L-Trp-L
      Tyr as the major cyclodipeptide. Total product yields of 46 to 211 mg/L E. coli
      culture were obtained. Our findings represent rare examples of CDPS family
      derived from actinobacteria that form various tryptophan-containing
      cyclodipeptides. Furthermore, this study highlights the potential of the
      microbial machinery for tryptophan-containing cyclodipeptide biosynthesis and
      provides valid experimental basis for further combination of these CDPS genes
      with other modification genes in synthetic biology.

PMID- 29574614
TI  - Two trehalose-hydrolyzing enzymes from Crenarchaeon Sulfolobus acidocaldarius
      exhibit distinct activities and affinities toward trehalose.
AB  - Two archaeal trehalase-like genes, Saci1250 and Saci1816, belonging to glycoside
      hydrolase family 15 (GH15) from the acidophilic Crenarchaeon Sulfolobus
      acidocaldarius were expressed in Escherichia coli. The gene products showed
      trehalose-hydrolyzing activities, and the names SaTreH1 and SaTreH2 were assigned
      to Saci1816 and Saci1250 gene products, respectively. These newly identified
      enzymes functioned within a narrow range of acidic pH values at elevated
      temperatures, which is similar to the behavior of Euryarchaeota Thermoplasma
      trehalases. SaTreH1 displayed high KM and kcat values, whereas SaTreH2 had lower
      KM and kcat values despite a high degree of identity in their primary structures.
      A mutation analysis indicated that two glutamic acid residues in SaTreH1, E374
      and E574, may be involved in trehalase catalysis because SaTreH1 E374Q and E574Q
      showed greatly reduced trehalose-hydrolyzing activities. Additional mutations
      substituting G573 and H575 residues with serine and glutamic acid residues,
      respectively, to mimic the TVN1315 sequence resulted in a decrease in trehalase
      activity and thermal stability. Taken together, the results indicated that
      Crenarchaea trehalases adopt active site structures that are similar to
      Euryarchaeota enzymes but have distinct molecular features. The identification of
      these trehalases could extend our understanding of the relationships between the
      structure and function of GH15 trehalases as well as other family enzymes and
      will provide insights into archaeal trehalose metabolism.

PMID- 29574615
TI  - Enhancement of HIV-1 VLP production using gene inhibition strategies.
AB  - Gag polyprotein from HIV-1 is able to generate virus-like particles (VLPs) when
      recombinantly expressed in animal cell platforms. HIV-1 VLP production in HEK293
      cells can be improved by the use of different strategies for increasing product
      titers. One of them is the so-called extended gene expression (EGE), based on
      repeated medium exchanges and retransfections of the cell culture to prolong the
      production phase. Another approach is the media supplementation with gene
      expression enhancers such as valproic acid and caffeine, despite their
      detrimental effect on cell viability. Valproic acid is a histone deacetylase
      inhibitor while caffeine has a phosphodiesterase inhibition effect. Here, the
      combination of the EGE protocol with additive supplementation to maximize VLP
      production is first tested. As an alternative to the direct additive
      supplementation, the replacement of these chemical additives by iRNA for
      obtaining the same inhibition action is also tested. The combination of the EGE
      protocol with caffeine and valproic acid supplementation resulted in a 1.5-fold
      improvement in HIV-1 VLP production compared with the EGE protocol alone,
      representing an overall 18-fold improvement over conventional batch cultivation.
      shRNAs encoded in the expression vector were tested to substitute valproic acid
      and caffeine. This novel strategy enhanced VLP production by 2.3 fold without any
      detrimental effect on cell viability (91.7%) compared with the batch cultivation
      (92.0%). Finally, the combination of shRNA with EGE resulted in more than 15.6
      fold improvement compared with the batch standard protocol traditionally used.
      The methodology developed enables the production of high titers of HIV-1 VLPs
      avoiding the toxic effects of additives.

PMID- 29574616
TI  - Transformation techniques for metabolic engineering of diatoms and haptophytes:
      current state and prospects.
AB  - Diatoms and haptophytes represent a key segment of the dominant phytoplankton
      communities that frequently form massive blooms in the photic zone of the ocean
      and are considered indicators of global climate changes. Diatoms and haptophytes
      also play a vital role in the biological carbon fixation in the carbon cycles.
      Carbon partitioning within diatoms and haptophytes possesses a wide range of
      chemical compounds and storage materials, such as lipids, carbohydrates, and
      chlorophyll. Among the marine microorganisms, diatoms and haptophytes have been
      recognized as promising sources of long- and very long-chain polyunsaturated
      fatty acids (PUFA). So far, a variety of approaches have been employed for
      genetic modification in the nuclei of diatoms and haptophytes. Studies on
      transformation and metabolic engineering in various intracellular genomes, such
      as chloroplast and mitochondria, are scarce. Particle bombardment, Agrobacterium
      and PEG-mediated gene transfer, and electroporation have been reported for
      foreign gene transformation into the diatoms and haptophytes. Antibiotics (G418
      and chloramphenicol) and herbicides (zeocin, hygromycin, and norflurazon) have
      been successfully demonstrated as the best selection markers. Despite the
      availability of a wide range of molecular tools for foreign gene expression in
      microalgae, very few promoters (lhcf1, nr, h4, ef2, fcp, and pds) have been
      reported for diatoms and haptophytes. Therefore, in this review, we first
      summarize the significant progress that has been achieved in transgene expression
      in diatoms and haptophytes and highlight the importance and availability of
      recently developed novel tools that are suitable for transgenic expression in
      diatoms and haptophytes.

PMID- 29574617
TI  - Mechanical properties of bio self-healing concrete containing immobilized
      bacteria with iron oxide nanoparticles.
AB  - Concrete is arguably one of the most important and widely used materials in the
      world, responsible for the majority of the industrial revolution due to its
      unique properties. However, it is susceptible to cracking under internal and
      external stresses. The generated cracks result in a significant reduction in the
      concrete lifespan and an increase in maintenance and repair costs. In recent
      years, the implementation of bacterial-based healing agent in the concrete matrix
      has emerged as one of the most promising approaches to address the concrete
      cracking issue. However, the bacterial cells need to be protected from the high
      pH content of concrete as well as the exerted shear forces during preparation and
      hardening stages. To address these issues, we propose the magnetic immobilization
      of bacteria with iron oxide nanoparticles (IONs). In the present study, the
      effect of the designed bio-agent on mechanical properties of concrete
      (compressive strength and drying shrinkage) is investigated. The results indicate
      that the addition of immobilized Bacillus species with IONs in concrete matrix
      contributes to increasing the compressive strength. Moreover, the precipitates in
      the bio-concrete specimen were characterized using scanning electron microscope
      (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS).
      The characterization studies confirm that the precipitated crystals in bio
      concrete specimen were CaCO3, while no precipitation was observed in the control
      sample.

PMID- 29574618
TI  - Safety and comfort of domestic bortezomib injection in real-life experience.
AB  - Despite novel agents, multiple myeloma is still an incurable disease, especially
      for elderly and frail patients, who are difficult to manage for concomitant
      comorbidities as the therapeutic options are limited and the response to
      chemotherapy is often short. We report our evaluations upon safety and efficacy
      of domestic subcutaneous bortezomib in elderly and frail patients candidate to
      bortezomib-melphalan-prednisone (VMP) regimen. We confirmed that overall
      incidence of adverse events, including peripheral neuropathy, was low, and in no
      case required admission to emergency service, contributing to reduce the rate of
      therapy discontinuation. These results confirm the effectiveness and safety of
      subcutaneous bortezomib, in a real-life-experience, and define a new possibility
      of safe auto-administration in a comfortable domestic setting. We suggest that
      domestic treatment can significantly improve the quality of life of the patients,
      avoiding unnecessary transfer to the hospital without reducing treatment
      efficacy.

PMID- 29574619
TI  - A qualitative analysis of oncology clinicians' perceptions and barriers for
      physical activity counseling in breast cancer survivors.
AB  - BACKGROUND: Few breast cancer survivors (BCS) engage in sufficient physical
      activity (PA) to gain physical and mental health benefits. This may be due to a
      lack of appropriate PA information and support. While key messengers of PA
      information could be oncology clinicians, many do not consistently counsel their
      patients on PA. PURPOSE: To examine factors affecting PA counseling in clinicians
      and inform future strategies. METHODS: Focus groups were conducted with
      clinicians (N = 27) at four cancer hospitals to better understand factors that
      affect PA counseling. Focus group discussions were transcribed verbatim and
      analyzed using inductive thematic analysis. RESULTS: Clinicians perceived a lack
      of training and knowledge related to PA and BCS. Clinicians also discussed being
      unsure of when to integrate PA counseling into different phases of survivorship.
      Similarly, clinicians experienced barriers from hospital administration to
      maintain patient flow in-clinic, which decreased opportunities for PA counseling.
      Additionally, lack of awareness of community-based programs within large areas
      served by hospitals also decreased clinicians' self-efficacy for counseling. In
      order to facilitate PA counseling, clinicians wanted resources that promote
      patient-managed PA, available on multiple platforms (e.g., printed and online).
      Continued education, highlighting recent research and effective implementation of
      PA, was noted as an important facilitator. CONCLUSIONS: Researchers are
      encouraged to develop research agendas and test educational strategies that are
      integrated into current practice, empirically test barriers that developed from
      this study with a larger, representative sample to determine salient barriers and
      develop PA counseling strategies that are clinician-initiated but not dependent
      on clinicians.

PMID- 29574620
TI  - Spatial modeling of rat bites and prediction of rat infestation in Peshawar
      valley using binomial kriging with logistic regression.
AB  - In this study, we propose to develop a geostatistical computational framework to
      model the distribution of rat bite infestation of epidemic proportion in Peshawar
      valley, Pakistan. Two species Rattus norvegicus and Rattus rattus are suspected
      to spread the infestation. The framework combines strengths of maximum entropy
      algorithm and binomial kriging with logistic regression to spatially model the
      distribution of infestation and to determine the individual role of environmental
      predictors in modeling the distribution trends. Our results demonstrate the
      significance of a number of social and environmental factors in rat infestations
      such as (I) high human population density; (II) greater dispersal ability of
      rodents due to the availability of better connectivity routes such as roads, and
      (III) temperature and precipitation influencing rodent fecundity and life cycle.

PMID- 29574622
TI  - Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis
      Patients Treated with Two Different Doses of Methotrexate in Combination with
      Adalimumab: Results From the MUSICA Trial.
AB  - INTRODUCTION: In patients with rheumatoid arthritis (RA), combination treatment
      with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy.
      From the patients' perspective, the impact of reduced MTX doses upon initiating
      adalimumab is not known. The objective was to evaluate the effects of low and
      high MTX doses in combination with adalimumab initiation on patient-reported
      outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe
      RA. METHODS: MUSICA was a randomized, double-blind, controlled trial evaluating
      the efficacy of 7.5 or 20 mg/week MTX, in combination with adalimumab for 24
      weeks in MTX-IR RA patients receiving prior MTX >= 15 mg/week for >= 12 weeks.
      PROs were recorded at each visit, including physical function, health-related
      quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment
      medication, sexual impairment due to RA, patient global assessment of disease
      activity (PGA), and patient pain. Last observation carried forward was used to
      account for missing values. RESULTS: At baseline, patients in both MTX dosage
      groups had similar demographics, disease characteristics, and PRO scores.
      Overall, initiation of adalimumab led to significant improvements from baseline
      in the PROs assessed for both MTX dosage groups. Improvements in presenteeism
      from baseline were strongly correlated with corresponding improvements in SF-36
      (vitality), pain, and physical function. Physical and mental well-being had a
      good correlation with improvement in sleep. Overall, improvements in disease
      activity from baseline were correlated with improvements in several PROs.
      CONCLUSIONS: The addition of adalimumab to MTX in MTX-IR patients with moderate
      to-severe RA led to improvements in physical function, quality-of-life, work
      productivity, quality of sleep, satisfaction with treatment medication, and
      sexual impairment due to RA, regardless of the concomitant MTX dosage. FUNDING:
      AbbVie. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01185288.

PMID- 29574621
TI  - Relating the multi-functionality of cytochrome c to membrane binding and
      structural conversion.
AB  - Cytochrome c is known as an electron-carrying protein in the respiratory chain of
      mitochondria. Over the last 20 years, however, alternative functions of this very
      versatile protein have become the focus of research interests. Upon binding to
      anionic lipids such as cardiolipin, the protein acquires peroxidase activity.
      Multiple lines of evidence suggest that this requires a conformational change of
      the protein which involves partial unfolding of its tertiary structure. This
      review summarizes the current state of knowledge of how cytochrome c interacts
      with cardiolipin-containing surfaces and how this affects its structure and
      function. In this context, we delineate partially conflicting results regarding
      the affinity of cytochrome c binding to cardiolipin-containing liposomes of
      different size and its influence on the structure of the protein and the
      morphology of the membrane.

PMID- 29574623
TI  - Genetic Risk Prediction for Primary and Secondary Prevention of Atherosclerotic
      Cardiovascular Disease: an Update.
AB  - PURPOSE OF REVIEW: This review aims to summarize the research on genetic risk
      scores and their ability to improve risk prediction in both a primary and a
      secondary prevention population. RECENT FINDINGS: Several groups have examined
      the role of genetic scores in different patient populations. Recent studies have
      capitalized on the growing number of identified genetic variants to construct
      polygenic risk scores that include hundreds and sometimes thousands of SNPs.
      Also, recent studies have demonstrated that individuals with high genetic risk
      scores can attenuate their risk with lifestyle modifications and with statins,
      for which the benefit of treatment may be greater in those at highest genetic
      risk. Genetic risk scores when added to existing clinical models appear to
      improve risk prediction, particularly in the setting of incident cardiovascular
      disease and may provide actionable information to optimize prevention early in
      life. Future research will need to establish how to best use this genetic risk
      information either as a means to further individualize treatment decisions or to
      better identify high-risk populations.

PMID- 29574624
TI  - Mitochondrial POLG related disorder presenting prenatally with fetal cerebellar
      growth arrest.
AB  - We report the prenatal findings of severe cerebellar growth arrest in two
      siblings with POLG1 mutations. The first presented with seizures and lactic
      acidosis immediately after premature birth and was diagnosed with mitochondrial
      disease on muscle biopsy. Molecular DNA analysis confirmed homozygous missense
      mutation in the POLG1 gene. The pregnancy of the second sibling was monitored
      closely by repeat fetal ultrasounds since the parents declined invasive testing.
      A detailed fetal ultrasound at 19 weeks gestation showed a small cerebellum with
      transcerebellar diameter (TCD) on axial cranial imaging, measuring below the 5th
      centile for gestational age. Molecular analysis confirmed the same homozygous
      familial mutation in the POLG1gene. This report further delineates the phenotypic
      features of the POLG related disorders and expands it to the prenatal era.
      Subsequent pregnancies were monitored by molecular analysis, using chorionic
      villus sampling (CVS).

PMID- 29574625
TI  - The cluster [Re6Se8I6]3- penetrates biological membranes: drug-like properties
      for CNS tumor treatment and diagnosis.
AB  - Tumorigenic cell lines are more susceptible to [Re6Se8I6]3- cluster-induced death
      than normal cells, becoming a novel candidate for cancer treatment. Still, the
      feasibility of using this type of molecules in human patients remains unclear and
      further pharmacokinetics analysis is needed. Using coupled plasma optical
      emission spectroscopy, we determined the Re-cluster tissue content in injected
      mice, as a biodistribution measurement. Our results show that the Re-cluster
      successfully reaches different tissues, accumulating mainly in heart and liver.
      In order to dissect the mechanism underlying cluster biodistribution, we used
      three different experimental approaches. First, we evaluate the degree of
      lipophilicity by determining the octanol/water partition coefficient. The cluster
      mostly remained in the octanol fraction, with a coefficient of 1.86 +/- 0.02,
      which indicates it could potentially cross cell membranes. Then, we measured the
      biological membrane penetration through a parallel artificial membrane
      permeability assays (PAMPA) assay. The Re-cluster crosses the artificial
      membrane, with a coefficient of 122 nm/s that is considered highly permeable. To
      evaluate a potential application of the Re-cluster in central nervous system
      (CNS) tumors, we analyzed the cluster's brain penetration by exposing cultured
      blood-brain-barrier (BBB) cells to increasing concentrations of the cluster. The
      Re-cluster effectively penetrates the BBB, reaching nearly 30% of the brain side
      after 24 h. Thus, our results indicate that the Re-cluster penetrates biological
      membranes reaching different target organs-most probably due to its lipophilic
      properties-becoming a promising anti-cancer drug with high potential for CNS
      cancer's diagnosis and treatment.

PMID- 29574626
TI  - Cardiac computed tomography compared with two-dimensional transesophageal
      echocardiography for the detection and assessment of atrial septal pouches.
AB  - The aim of this study is to compare the two-dimensional transesophageal
      echocardiography (2D-TEE) with multi-slice computed tomography (MSCT) and with
      autopsied material to evaluate the ability and precision of the imaging methods
      for the detection and assessment of septal pouch (SP). One hundred and fifty
      patients that underwent both 2D-TEE and MSCT and 50 autopsied human hearts were
      investigated. In MSCT, the interatrial septum was classified as a left SP in
      37.3%, right SP in 3.3%, and patent foramen ovale (PFO) channel in 3.3%. In 2D
      TEE, the interatrial septum was classified as a left SP in 39.3%, right SP in
      11.3%, double SP in 4.7%, and PFO channel in 2.0%. The weighted kappa coefficient
      between MSCT and 2D-TEE in assessing the septum morphology was 0.59. The
      prevalence of the left SP is lower when it is evaluated by MSCT or 2D-TEE than by
      anatomical study, but this difference is insignificant (37.3% vs. 44.0%, p =
      0.40, and 39.3% vs. 44.0%, p = 0.56, respectively). The prevalence of left SPs is
      lower when detected by MSCT or 2D-TEE than during autopsy, but the difference is
      statistically insignificant (37.3% vs. 44.0%, p = 0.40, and 39.3% vs. 44.0%, p =
      0.56, respectively). Both 2D-TEE and MSCT are comparable techniques for detecting
      left-sided SPs with the insignificant lower prevalence of detecting left-sided
      SPs compared to autopsied material. However, TEE with the contrast seems to be
      superior over MSCT due to the possibility of unambiguous PFO channel detection.
      Therefore, TEE with contrast should be preferred over MSCT in the identification
      of left-sided SPs.

PMID- 29574627
TI  - Comparison of Vela and holmium laser enucleation of the prostate: a retrospective
      clinical trial with a 12-month follow-up.
AB  - PURPOSE: This study aimed to estimate the validity and applicability of Vela
      laser enucleation of the prostate (VoLEP) in the management of benign prostatic
      hyperplasia (BPH). METHODS: A retrospective chart review of 112 patients with BPH
      who underwent VoLEP (n = 60) or holmium laser enucleation of the prostate (HoLEP)
      (n = 56) was conducted at our institution from January 2015 to June 2015. The
      general and perioperative characteristics of the patients were collected. The 12
      month follow-up data, including the lower urinary tract symptom (LUTS) indexes
      (International Prostate Symptom Score [I-PSS], quality-of-life [QoL] score and
      maximum flow rate [Qmax]), as well as rates of perioperative and late
      complications, were analyzed. RESULTS: No significant differences were observed
      in pre- and perioperative parameters, including operation time (58.05 +/- 10.14
      vs. 60.14 +/- 12.30 min, P = 0.44), serum sodium decrease (3.49 +/- 0.83 vs. 3.48
      +/- 0.84 mmol/L, P = 0.97), hemoglobin decrease (1.28 +/- 0.38 vs. 1.24 +/- 0.77
      g/dL, P = 0.71), catheterization time (3.63 +/- 1.10 vs. 3.89 +/- 1.11 days, P =
      0.21) and hospital stay (4.57 +/- 1.25 vs. 4.68 +/- 1.18 days, P = 0.63) between
      the two groups of patients. Compared with the HoLEP group, the noise during
      operation was lower in VoLEP group (47.22 +/- 10.31 vs. 59.45 +/- 9.65 db, P <
      0.05). During 1, 6 and 12 months of follow-up visits, the LUTS indexes (I-PSS,
      QoL score and Qmax) were remarkably improved in both groups when comparing with
      the baseline values. Furthermore, LUTS indexes were comparable in both groups (P
      > 0.05). CONCLUSION: Similarly as the holmium laser, the Vela laser is a potent,
      safe, efficient durable and surgical treatment option for minimally invasive
      surgery in patients with BPH-induced LUTS.

PMID- 29574628
TI  - Amyloid-beta Increases Tau by Mediating Sirtuin 3 in Alzheimer's Disease.
AB  - Increasing evidence indicates that sirtuin 3 (Sirt3) has neuroprotective effects
      in regulating oxidative stress and energy metabolism, both of which are involved
      in the pathogenesis of Alzheimer's disease (AD). However, it is unclear whether
      Sirt3 is associated with cognitive performance and pathological changes in AD. We
      conducted a case-control study of the postmortem brains of AD (n = 16), mild
      cognitive impairment (n = 13), and age- and education-matched cognitively normal
      (CN, n = 11) subjects. We measured the mRNA and protein levels of Sirt3 and
      assessed their association with cognitive performance and AD pathology. In an ex
      vivo model of cortical neurons from transgenic mice that carry human tau protein,
      we modified Sirt3 expression by genetic knockdown and knock-in to investigate the
      cause-effect relationship between Sirt3 and tau. Sirt3 levels were reduced in the
      entorhinal cortex, the middle temporal gyrus, and the superior frontal gyrus of
      AD subjects compared to those of CN. This reduction was associated with poorer
      test scores of neuropsychological evaluation and the severity of tau pathology.
      Further study with genetic manipulation of Sirt3 revealed that amyloid-beta
      increased levels of total tau acetylated tau through its modulation of Sirt3.
      These data suggest that reduction of Sirt3 is critically involved in pathogenesis
      of AD.

PMID- 29574629
TI  - Exercise Rehabilitation Attenuates Cognitive Deficits in Rats with Traumatic
      Brain Injury by Stimulating the Cerebral HSP20/BDNF/TrkB Signalling Axis.
AB  - Physical exercise (PE) is an effective method for improving cognitive function
      among patients with traumatic brain injury (TBI). We previously demonstrated that
      PE with an infrared-sensing running wheel (ISRW) system provides strong
      neuroprotection in an experimental animal model of stroke. In this study, we used
      fluid percussion injury in rats to simulate mild TBI. For rats, we used both
      passive avoidance learning and the Y-maze tests to evaluate cognitive function.
      We investigated whether PE rehabilitation attenuated cognitive deficits in rats
      with TBI and determined the contribution of hippocampal and cortical expression
      of heat shock protein 20 (HSP20) to PE-mediated cognitive recovery. In addition
      to increasing hippocampal and cortical expression of HSP20, brain-derived
      neurotrophic factor (BDNF), and the tropomyosin receptor kinase B (TrkB) ratio,
      PE rehabilitation significantly attenuated brain contusion and improved cognitive
      deficits in the rat model. Furthermore, reducing hippocampal and cortical
      expression of HSP20 with an intracerebral injection of pSUPER hsp20 small
      interfering RNA significantly diminished the PE-induced overexpression of
      hippocampal and cortical BDNF and the TrkB ratio and also reversed the beneficial
      effect of PE in reducing neurotrauma and the cognitive deficits. A positive
      Pearson correlation was found between HSP20 and BDNF, as well as between HSP20
      and TrkB, in the hippocampal and cortical tissues. We thus conclude that post
      ischaemic ISRW exercise rehabilitation attenuates cognitive deficits, as well as
      brain contusions, in TBI rats by stimulating the cerebral HSP20/BDNF/TrkB
      signalling axis.

PMID- 29574630
TI  - P2Y12 but not P2Y13 Purinergic Receptor Controls Postnatal Rat Retinogenesis In
      Vivo.
AB  - Adenine nucleotides through P2Y1 receptor stimulation are known to control
      retinal progenitor cell (RPC) proliferation by modulating expression of the
      p57KIP2, a cell cycle regulator. However, the role of Gi protein-coupled P2Y12
      and P2Y13 receptors also activated by adenine nucleotides in RPC proliferation is
      still unknown. Gene expression of the purinergic P2Y12 subtype was detected in
      rat retina during early postnatal days (P0 to P5), while expression levels of
      P2Y13 were low. Immunohistochemistry assays performed with rat retina on P3
      revealed P2Y12 receptor expression in both Ki-67-positive cells in the
      neuroblastic layer and Ki-67-negative cells in the ganglion cell layer and inner
      nuclear layer. Nonetheless, P2Y13 receptor expression could not be detected in
      any stratum of rat retina. Intravitreal injection of PSB 0739 or clopidogrel,
      both selective P2Y12 receptor antagonists, increased by 20 and 15%, respectively,
      the number of Ki-67-positive cells following 24 h of exposure. Moreover, the
      P2Y12 receptor inhibition increased cyclin D1 and decreased p57KIP2 expression.
      However, there were no changes in the S phase of the cell cycle (BrdU-positive
      cells) or in mitosis (phospho-histone-H3-positive cells). Interestingly, an
      increase in the number of cyclin D1/TUNEL-positive cells after treatment with PSB
      0739 was observed. These data suggest that activation of P2Y12 receptors is
      required for the successful exit of RPCs from cell cycle in the postnatal rat
      retina.

PMID- 29574632
TI  - An integrate-and-fire model to generate spike trains with long-range dependence.
AB  - Long-range dependence (LRD) has been observed in a variety of phenomena in
      nature, and for several years also in the spiking activity of neurons. Often,
      this is interpreted as originating from a non-Markovian system. Here we show that
      a purely Markovian integrate-and-fire (IF) model, with a noisy slow adaptation
      term, can generate interspike intervals (ISIs) that appear as having LRD. However
      a proper analysis shows that this is not the case asymptotically. For comparison,
      we also consider a new model of individual IF neuron with fractional (non
      Markovian) noise. The correlations of its spike trains are studied and proven to
      have LRD, unlike classical IF models. On the other hand, to correctly measure
      long-range dependence, it is usually necessary to know if the data are
      stationary. Thus, a methodology to evaluate stationarity of the ISIs is presented
      and applied to the various IF models. We explain that Markovian IF models may
      seem to have LRD because of non-stationarities.

PMID- 29574631
TI  - Oxidative stress as a possible mechanism of statin-induced myopathy.
AB  - Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase,
      are the most widely used drugs for treating hypercholesterolemia. However,
      statins can cause disabling myopathy as their main adverse effect. Several
      molecular mechanisms underlie the statin-induced myopathy including the decrease
      in the levels of essential mevalonate and cholesterol derivatives. This review
      discusses a further mechanism involving the loss of other anti-oxidant defenses
      besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount
      of reactive oxygen species (ROS). Therefore, to maintain their function, skeletal
      muscles need a high level of anti-oxidants.

PMID- 29574633
TI  - A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1
      Receptor Agonists in Japanese Patients with Type 2 Diabetes.
AB  - INTRODUCTION: Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1
      (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to
      head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs)
      in a Japanese population, a network meta-analysis (NMA) was performed. The
      objective was to assess the relative efficacy and safety of semaglutide QW vs GLP
      1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on
      the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. METHODS:
      A systematic review (SR) and supplementary Japanese searches were conducted to
      identify trials of GLP-1 RAs in Japanese patients on diet and exercise, who have
      previously received 0-1 oral antidiabetic drugs (OADs). Data at 52-56 weeks were
      extracted for the following outcomes (feasible for analysis in an NMA): glycated
      hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, systolic blood pressure
      (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a
      Bayesian framework. RESULTS: Four trials, identified from the SR and Japanese
      specific searches, were relevant for inclusion in the NMA. When compared to
      dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant
      reductions in HbA1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03
      mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of
      patients achieving a HbA1c level < 7% (53 mmol/mol) or the risk of overall
      hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg
      QW. CONCLUSION: Overall, semaglutide 0.5 mg QW was associated with significant
      reductions from baseline in HbA1c, weight, SBP, and FPG compared with dulaglutide
      0.75 mg QW in Japanese patients with T2DM. These data may provide valuable
      evidence for clinical decision-making, cost-effectiveness analyses, and health
      technology appraisal (HTA) requirements. FUNDING: Novo Nordisk Pharma Ltd.

PMID- 29574634
TI  - Basal Insulin Intensification in Patients with Type 2 Diabetes: A Review.
AB  - : As the number of people living with type 2 diabetes (T2D) continues to rise,
      managing their complex needs presents an increasing challenge to physicians.
      While treatment guidelines provide evidence-based guidance, they are not
      prescriptive-rather they emphasize individualization of management based on a
      patient's clinical needs and preferences. Physicians, therefore, need to be fully
      aware of the advantages and disadvantages of the multiple and increasing
      treatment options available to them at each stage of the disease. The progressive
      nature of T2D means that treatment with basal insulin will become inevitable for
      many patients, while for some patients basal insulin alone will eventually be
      insufficient for maintaining glycemic targets. Recent guidelines recommend two
      basic approaches for intensifying basal insulin: the use of rapid-acting insulin,
      either as additional prandial injections or as part of premix (biphasic) insulin;
      and the addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to the
      insulin therapy, which can be administered via subcutaneous injection once or
      twice daily, or weekly depending on formulation. More recently, two fixed-ratio
      combinations of basal insulin and a GLP-1 RA that allow for once-daily dosing
      have been approved. Each of these approaches has potential benefits and
      drawbacks, particularly in terms of risk for hypoglycemia, weight change,
      convenience, and side effects. Understanding these differences is central to
      guiding patient and physician choice. This article discusses the rationale,
      advantages, disadvantages, and implementation of currently available strategies
      for basal insulin treatment intensification in patients with T2D. FUNDING: Sanofi
      US, Inc.

PMID- 29574635
TI  - Relative Contribution of Fasting and Postprandial Blood Glucose in Overall
      Glycemic Control: Post Hoc Analysis of a Phase IV Randomized Trial.
AB  - INTRODUCTION: Few prospective clinical trials have investigated the role of
      fasting blood glucose (FBG) and/or postprandial glucose (PPG) in assessing
      overall glycemic control by using different insulin regimens. In the present post
      hoc analysis, we assessed the contribution of FBG and/or PPG in overall glycemic
      control in Chinese patients under insulin treatment. METHODS: CLASSIFY is a phase
      IV, randomized, open-label, 26-week, parallel-arm, treat-to-target,
      multinational, controlled study in patients with type 2 diabetes mellitus to
      compare the efficacy and safety of insulin lispro mix 25 (LM25) and insulin
      lispro mix 50 (LM50) as starter insulins. Insulin was titrated with an aim to
      target pre-meal blood glucose (BG) levels at > 3.9 and <= 6.1 mmol/L before
      breakfast and dinner. The primary outcome assessed was the change in HbA1c from
      baseline. RESULTS: Chinese patients contributed 38.7% (N = 156) of the total
      population. The majority of patients were male (52.6%). The mean (SD) body mass
      index was 24.54 (3.04) kg/m2 and mean (SD) HbA1c was 8.54 (1.10) % at baseline.
      At week 26, LM50 showed a significantly greater reduction from baseline in HbA1c
      (- 2.03% vs - 1.55%, P < 0.001), average daily BG (- 3.21 vs - 2.34 mmol/L, P <
      0.001), average post-meal BG (- 3.58 vs - 2.39 mmol/L, P < 0.001), and average
      prandial BG excursion (- 1.01 vs - 0.22 mmol/L, P = 0.006) than the LM25 group.
      The reductions in average pre-meal BG (- 2.59 vs - 2.28 mmol/L, P = 0.137) were
      not significantly different between the groups. The proportion of patients
      achieving HbA1c targets (< 7% or <= 6.5%) without nocturnal hypoglycemia or
      weight gain was greater (P < 0.05) with LM50 compared with LM25. CONCLUSION: LM50
      achieved better overall glycemic control than LM25 as a starter insulin in
      Chinese patients, which may be due to greater improvement in PPG levels. TRIAL
      REGISTRATION: Clinicaltrials.gov identification number: NCT01773473. FUNDING: Eli
      Lilly and Company, Shanghai, China.

PMID- 29574636
TI  - GPCRs profiling and identification of GPR110 as a potential new target in HER2+
      breast cancer.
AB  - PURPOSE: G protein-coupled receptors (GPCRs) represent the largest family of
      druggable targets in human genome. Although several GPCRs can cross-talk with the
      human epidermal growth factor receptors (HERs), the expression and function of
      most GPCRs remain unknown in HER2+ breast cancer (BC). In this study, we aimed to
      evaluate gene expression of GPCRs in tumorigenic or anti-HER2 drug-resistant
      cells and to understand the potential role of candidate GPCRs in HER2+ BC.
      METHODS: Gene expression of 352 GPCRs was profiled in Aldeflur+ tumorigenic
      versus Aldeflur- population and anti-HER2 therapy-resistant derivatives versus
      parental cells of HER2+ BT474 cells. The GPCR candidates were confirmed in 7
      additional HER2+ BC cell line models and publicly available patient dataset.
      Anchorage-dependent and anchorage-independent cell growth, mammosphere formation,
      and migration/invasion were evaluated upon GPR110 knockdown by siRNA in BT474 and
      SKBR3 parental and lapatinib+ trastuzumab-resistant (LTR) cells. RESULTS:
      Adhesion and class A GPCRs were overexpressed in Aldeflur+ and anti-HER2 therapy
      resistant population of BT474 cells, respectively. GPR110 was the only GPCR
      overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population in BT474,
      SKBR3, HCC1569, MDA-MB-361, AU565, and/or HCC202 cells and in HER2+ BC subtype in
      patient tumors. Using BT474 and SKBR3 parental and LTR cells, we found that
      GPR110 knockdown significantly reduced anchorage-dependent/independent cell
      growth as well as migration/invasion of parental and LTR cells and mammosphere
      formation in LTR derivatives and not in parental cells. CONCLUSION: Our data
      suggest a potential role of GPR110 in tumorigenicity and in tumor cell
      dissemination in HER2+ BC.

PMID- 29574637
TI  - Validation of a personalized risk prediction model for contralateral breast
      cancer.
AB  - PURPOSE: Women diagnosed with unilateral breast cancer are increasingly choosing
      to remove their other unaffected breast through contralateral prophylactic
      mastectomy (CPM) to reduce the risk of contralateral breast cancer (CBC). Yet a
      large proportion of CPMs are believed to be medically unnecessary. Thus, there is
      a pressing need to educate patients effectively on their CBC risk. We had earlier
      developed a CBC risk prediction model called CBCRisk based on eight personal risk
      factors. METHODS: In this study, we validate CBCRisk on independent clinical data
      from the Johns Hopkins University (JH) and MD Anderson Cancer Center (MDA). Women
      whose first breast cancer diagnosis was either invasive and/or ductal carcinoma
      in situ and whose age at first diagnosis was between 18 and 88 years were
      included in the cohorts because CBCRisk was developed specifically for these
      women. A woman who develops CBC is called a case whereas a woman who does not is
      called a control. The cohort sizes are 6035 (with 117 CBC cases) for JH and 5185
      (with 111 CBC cases) for MDA. We computed the relevant calibration and validation
      measures for 3- and 5-year risk predictions. RESULTS: We found that the model
      performs reasonably well for both cohorts. In particular, area under the receiver
      operating characteristic curve for the two cohorts range from 0.61 to 0.65.
      CONCLUSIONS: With this independent validation, CBCRisk can be used confidently in
      clinical settings for counseling BC patients by providing their individualized
      CBC risk. In turn, this may potentially help alleviate the rate of medically
      unnecessary CPMs.

PMID- 29574638
TI  - Long-Chain Omega-3 Polyunsaturated Fatty Acids Modulate Mammary Gland Composition
      and Inflammation.
AB  - Studies in rodents have shown that dietary modifications as mammary glands (MG)
      develop, regulates susceptibility to mammary tumor initiation. However, the
      effects of dietary PUFA composition on MGs in adult life, remains poorly
      understood. This study investigated morphological alterations and inflammatory
      microenvironments in the MGs of adult mice fed isocaloric and isolipidic liquid
      diets with varying compositions of omega (omega)-6 and long-chain (Lc)-omega3FA
      that were pair-fed. Despite similar consumption levels of the diets, mice fed the
      omega-3 diet had significantly lower body-weight gains, and abdominal-fat and
      mammary fat pad (MFP) weights. Fatty acid analysis showed significantly higher
      levels of Lc-omega-3FAs in the MFPs of mice on the omega-3 diet, while in the
      MFPs from the omega-6 group, Lc-omega-3FAs were undetectable. Our study revealed
      that MGs from omega-3 group had a significantly lower ductal end-point density,
      branching density, an absence of ductal sprouts, a thinner ductal stroma, fewer
      proliferating epithelial cells and a lower transcription levels of estrogen
      receptor 1 and amphiregulin. An analysis of the MFP and abdominal-fat showed
      significantly smaller adipocytes in the omega-3 group, which was accompanied by
      lower transcription levels of leptin, IGF1, and IGF1R. Further, MFPs from the
      omega-3 group had significantly decreased numbers and sizes of crown-like
      structures (CLS), F4/80+ macrophages and decreased expression of proinflammatory
      mediators including Ptgs2, IL6, CCL2, TNFalpha, NFkappaB, and IFNgamma. Together,
      these results support dietary Lc-omega-3FA regulation of MG structure and density
      and adipose tissue inflammation with the potential for dietary Lc-omega-3FA to
      decrease the risk of mammary gland tumor formation.

PMID- 29574639
TI  - Toxicity evaluation of 4,4'-di-CDPS and 4,4'-di-CDE on green algae Scenedesmus
      obliquus: growth inhibition, change in pigment content, and oxidative stress.
AB  - Polychlorinated diphenyl sulfides and polychlorinated diphenyl ethers are two
      types of dioxin-like pollutants, which are prevalent in aquatic environments.
      However, to date, limited information is available regarding their toxicity to
      green algae. In this study, growth inhibition, effect on pigment content, and
      oxidative stress potentials of 4,4'-di-CDPS and 4,4'-di-CDE on green algae
      Scenedesmus obliquus were investigated. The results indicate that the EC50 values
      of 4,4'-di-CDPS after 24, 48, 72, and 96 h of exposure were 1.736, 1.172, 0.994,
      and 0.820 mg/L, while the corresponding values for 4,4'-di-CDE were 0.697, 1.087,
      0.833, and 0.327 mg/L. As compared to the control group, most of the measured
      pigment content in algal cells significantly decreased after 96-h exposure to
      these two chemicals, suggesting their suppressive capability on the
      photosynthesis process in algal cells. Additionally, oxidative stress occurred as
      demonstrated by the significantly inhibited activities of the antioxidant enzymes
      (total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase
      (GPx)), and high increases in malondialdehyde (MDA) content in all 4,4'-di-CDE
      treated groups and some moderate-dose and high-dose treatments with 4,4'-di-CDPS.
      Acute toxicity tests and biochemical analysis showed that 4,4'-di-CDE was more
      toxic than 4,4'-di-CDPS on S. obliquus.

PMID- 29574640
TI  - Quantitative structure-activity relationship for the partition coefficient of
      hydrophobic compounds between silicone oil and air.
AB  - The silicon oil-air partition coefficients (KSiO/A) of hydrophobic compounds are
      vital parameters for applying silicone oil as non-aqueous-phase liquid in
      partitioning bioreactors. Due to the limited number of KSiO/A values determined
      by experiment for hydrophobic compounds, there is an urgent need to model the
      KSiO/A values for unknown chemicals. In the present study, we developed a
      universal quantitative structure-activity relationship (QSAR) model using a
      sequential approach with macro-constitutional and micromolecular descriptors for
      silicone oil-air partition coefficients (KSiO/A) of hydrophobic compounds with
      large structural variance. The geometry optimization and vibrational frequencies
      of each chemical were calculated using the hybrid density functional theory at
      the B3LYP/6-311G** level. Several quantum chemical parameters that reflect
      various intermolecular interactions as well as hydrophobicity were selected to
      develop QSAR model. The result indicates that a regression model derived from
      logKSiO/A, the number of non-hydrogen atoms (#nonHatoms) and energy gap of ELUMO
      and EHOMO (ELUMO-EHOMO) could explain the partitioning mechanism of hydrophobic
      compounds between silicone oil and air. The correlation coefficient R2 of the
      model is 0.922, and the internal and external validation coefficient, Q2LOO and
      Q2ext , are 0.91 and 0.89 respectively, implying that the model has satisfactory
      goodness-of-fit, robustness, and predictive ability and thus provides a robust
      predictive tool to estimate the logKSiO/A values for chemicals in application
      domain. The applicability domain of the model was visualized by the Williams
      plot.

PMID- 29574641
TI  - High performance of 3D porous graphene/lignin/sodium alginate composite for
      adsorption of Cd(II) and Pb(II).
AB  - A novel adsorbent, three-dimensional porous graphene/lignin/sodium alginate
      nanocomposite (denoted as 3D PG/L/SA) was fabricated by hydrothermal
      polymerization of lignin and sodium alginate in the presence of graphene oxide
      (GO) in an aqueous system. Fourier transform infrared spectra, thermo-gravimetric
      analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy were
      employed to characterize the morphology and structure of this novel functional
      PG/L/SA nanocomposite. A series of adsorption experiments for cleanup of Cd(II)
      and Pb(II) were conducted to investigate the effects of lignin and sodium
      alginate on the graphene structure. It was found that PG/L/SA showed a
      significant increase in adsorption capacity contrast to porous graphene (PG). The
      as-prepared material achieved the adsorption capacity for Cd(II) and Pb(II) of
      79.88 and 226.24 mg/g, respectively. Meanwhile, the adsorption process matched
      well with the Langmuir isotherm model and the pseudo-second-order kinetic model.
      Studies were also conducted to demonstrate the applicability of the sorbent to
      the removal of heavy metal ions from metal smelting wastewater.

PMID- 29574642
TI  - Crystallization of microporous TiO2 through photochemical deposition of Pt for
      photocatalytic degradation of volatile organic compounds.
AB  - The photocatalytic mineralization efficiency of volatile organic compounds (VOCs)
      is determined by adsorption of reactants, separation of charge carriers, and
      reaction activity of catalyst surface. Herein, we provide a strategy to
      synthesize a novel catalyst, namely, PhPt-Micro, which is characterized by high
      adsorption ability, charge separation efficiency, and surface reaction activity.
      Toluene was chosen as the model VOC. The effects of photochemical deposition of
      Pt on the physical properties of microporous amorphous TiO2 (Micro) and toluene
      mineralization were studied using N2 adsorption/desorption, transmission electron
      microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, GC-flame
      ionization detection, and surface photovoltage spectroscopy (SPS) analyses. After
      photochemical treatment, the structure of Micro was optimized, and Pt
      nanoparticles were successfully deposited at the outlet of electrons on the
      catalyst surface. SPS result proved that the optimized structure enhanced the
      separation efficiency of charge carriers and the migration of photo-generated
      electrons to the PhPt-Micro surface. The quasi-equilibrium adsorption amount of
      toluene over PhPt-Micro was two times higher than that with commercial nano TiO2
      (P25). The micropores concentrated toluene on the catalyst surface and hindered
      intermediate desorption. The mineralization efficiency of toluene over PhPt-Micro
      was 2.4 and 5.9 times higher than those over Micro and P25, respectively.

PMID- 29574643
TI  - Effects of monoterpenes on mortality, growth, fecundity, and ovarian development
      of Bactrocera zonata (Saunders) (Diptera: Tephritidae).
AB  - The peach fruit fly (PFF), Bactrocera zonata, is a serious insect pest infesting
      fruits and vegetables. The insecticidal activity of three monoterpenes, namely,
      (R)-camphor, (R)-carvone, and (1R,2S,5R)-menthol, was evaluated on the second
      instar larvae of B. zonata. In addition, the latent effects of monoterpenes on
      pupation, adult emergence, deformation, oviposition, adult longevity, and ovarian
      development were also examined. The three tested monoterpenes showed pronounced
      insecticidal activity against B. zonata larvae with (R)-carvone being the most
      potent toxicant. When the second-instar larvae of B. zonata were treated with
      monoterpenes at concentrations of 20, 50, and 70 mg/kg for 72 h, significant
      reduction in pupation and adult emergence was observed. The three monoterpenes
      caused complete suppression of adult emergence at 100 mg/kg. Moreover,
      monoterpenes induced complete inhibition of egg deposition at all tested
      concentrations. Some adult deformations were also noticed at 20, 50, and 70
      mg/kg. However, (R)-carvone was more effective than (1R,2S,5R)-menthol and (R)
      camphor on the examined biological parameters. On the other hand, histological
      examination of the ovaries of emerged females from larvae that fed on diet
      treated with (R)-carvone, (1R,2S,5R)-menthol, and (R)-camphor at 20 and 50 mg/L
      indicated that both concentrations caused retardation in the development of
      ovarioles. It is clear that all the egg chambers are empty; the germarium region
      is constricted at base due to the failure of oocyte formation. Many vacant spaces
      were present between ovarioles.

PMID- 29574644
TI  - Characteristics of arsenic in humic substances extracted from natural organic
      sediments.
AB  - The stability and dispersion of naturally occurring As have been receiving
      increasing attention, because As is toxic and its contamination is a widespread
      problem in many countries. This study investigated As fractionation and
      speciation in organic sediments collected from different depositional settings to
      elucidate the existence of stable As in humic substances. Eleven organic sediment
      samples were collected from marine and terrestrial alluvial regions in Hokkaido
      prefecture, Japan, and the chemical fraction of As and species of humic
      substances were identified by sequential extraction. In addition, stable As bound
      in organic matter was evaluated by FT-IR spectroscopy. The As fraction mainly
      comprised inorganic substances, especially sulfur, iron, and manganese, and
      terrestrial sediments (lacustrine and inland deposits) were rich in sulfides and
      Fe and Al (hydr)oxides. When the residual fraction was excluded, the organic
      fraction of As was higher in seawater sediments than in terrestrial sediments.
      Among humic substances, cellulose, humic acid, and hydrophilic fulvic acid were
      clearly associated with As accumulation, and As speciation showed that the As was
      of organic origin. Cellulose, an organic compound of plant origin, was abundant
      in As=S and As (III)=O bonds, and As accumulation was higher in sulfur-rich peat
      sediments, corresponding with the physiological activities of As in plants.
      Hydrophilic fulvic acid and humic acid in these sediments, originating from small
      animals and microorganisms in addition to plants, denote higher As contents and
      abound in As (III, V)=C and C-H, CH3 bonds even in sulfur-rich sediments. The
      methylated As bonds reflect the ecological transition of organisms.

PMID- 29574645
TI  - Environmental asbestos exposure and mesothelioma cases in Bari, Apulia region,
      southern Italy: a national interest site for land reclamation.
AB  - Asbestos is an environmental carcinogen, and asbestos-related diseases are a
      global-scale public health issue. We report three cases (one male and two
      females) of pleural malignant mesothelioma (PMM) caused by environmental asbestos
      exposure reported by the Apulia Regional Operating Centre (COR) to the National
      Mesothelioma Registry (ReNaM). The patients revealed no history of asbestos
      exposure even after detailed assessment. The environmental (neighborhood)
      asbestos exposure for each of the three cases was due to both the residential
      history of the subjects and their workplace, close to a military barracks, at a
      distance of between 45 and 100 m. Moreover, in addition to this new source of
      pollution, an asbestos cement factory was located in the urban area of Bari
      municipality, in the Apulia region, southern Italy. Environmental
      residential/neighborhood asbestos exposure in the city of Bari, a contaminated
      area classified as a site of national concern for land reclamation, is discussed
      also with reference to the military barracks.

PMID- 29574646
TI  - Aliphatic and aromatic biomarkers for fingerprinting of weathered chemically
      dispersed oil.
AB  - This study evaluated the applicability of eight types of biomarkers namely,
      adamantanes, diamantanes, sesquiterpanes, steranes, terpanes, TA-steranes, MA
      steranes, and alkylated PAHs, to characterize chemically dispersed oil (CDO)
      after the 60-day weathering. The stability of diagnostic ratios of the selected
      biomarkers was evaluated and summarized. The results indicated that the
      concentrations of biomarkers with low molecular weight, such as adamantanes,
      diamantanes, and sesquiterpanes, in CDO were markedly affected by weathering and
      the associated diagnostic ratios were changed extensively. Most of the alkylated
      PAHs were degraded during weathering as well. These biomarkers thus were not
      recommended for characterizing CDO. The majority of the terpanes, steranes, TA
      steranes, and MA-steranes could be used for weathered CDO fingerprinting due to
      the relatively stable diagnostic ratios. The findings could help to identify
      applicable biomarkers for fingerprinting of weathered dispersed oil.

PMID- 29574647
TI  - Fine particulate matter (PM2.5) in a compost facility: heavy metal contaminations
      and health risk assessment, Tehran, Iran.
AB  - The aim of this study was to evaluate the concentration of PM2.5 particles,
      potential sources, and determination of health risk assessment of heavy metals in
      various parts of composting facilities of Tehran's Kahrizak. A total of 60 PM2.5
      particle samples were collected every 3 days from January to March 2016. To
      analyze the heavy metals, inductively coupled plasma atomic emission spectroscopy
      (ICP-AES) was applied. SEM-EDX analysis indicated that metals of Al, Si, Mg, Na,
      Au, S, Ca, K, and Co were dominant in the structure of particles. The
      concentration of PM2.5 was found to be the highest in the final processing site
      (c), followed by primary processing site (a) and the aerated site (b). The mean
      concentrations of Al and Fe in all sampling sites of a, b, and c were 7.46 +/-
      2.73, 1.48 +/- 0.59, 24.30 +/- 8.23 MUg/m3 and 4.97 +/- 2.83, 1.33 +/- 0.48,
      16.48 +/- 7.36, respectively. The enrichment factor order of the trace elements
      was as follows: Cd > As > Pb > Zn > Cu > V > Cr > Ni > Mn > Fe > Al, with the
      highest EF value exceeding 10,000 for Cd at the a site. For all sampling sites in
      composting facilities, the cancer risk was more than > 1 * 10-4 as posed by the
      total of five carcinogenic metals (Pb, Cr, As, Ni, and Cd), indicating that risk
      factors were not negligible.

PMID- 29574648
TI  - Aqueous multivariate phototransformation kinetics of dissociated tetracycline:
      implications for the photochemical fate in surface waters.
AB  - Antibiotics are ubiquitous pollutants in aquatic systems and can exist as
      different dissociated species depending on the water pH. New knowledge of their
      multivariate photochemical behavior (i.e., the photobehavior of different ionized
      forms) is needed to improve our understanding on the fate and possible
      remediation of these pharmaceuticals in surface and waste waters. In this study,
      the photochemical degradation of aqueous tetracycline (TC) and its dissociated
      forms (TCH20, TCH-, and TC2-) was investigated. Simulated sunlight experiments
      and matrix calculations indicated that the three dissociated species had
      dissimilar photolytic kinetics and photooxidation reactivities. TC2-
      photodegraded the fastest due to apparent photolysis with a kinetic constant of
      0.938 +/- 0.021 min-1, followed by TCH- (0.020 +/- 0.005 min-1) and TCH20 (0.012
      +/- 0.001 min-1), whereas TCH- was found to be the most highly reactive toward
      *OH (105.78 +/- 3.40 M-1 s-1), and TC2- reacted the fastest with 1O2 (344.96 +/-
      45.07 M-1 s-1). Water with relatively high pH (e.g., ~ 8-9) favors the
      dissociated forms of TCH- and TC2- which are most susceptible to photochemical
      loss processes compared to neutral TC. The calculated corresponding environmental
      half-lives (t1/2,E) in sunlit surface waters ranged from 0.05 h for pH = 9 in
      midsummer to 3.68 h for pH = 6 in midwinter at 45 degrees  N latitude. The
      process was dominated by apparent photolysis (especially in summer, 62-91%),
      followed by 1O2 and *OH oxidation. Adjusting the pH to slightly alkaline
      conditions prior to UV or solar UV light treatment may be an effective way of
      enhancing the photochemical removal of TC from contaminated water. Graphical
      abstract Aqueous multiple photochemical behavior of dissociated tetracycline
      (TCH20, TCH-, and TC2-) is first comprehensively reported on revealing the
      phototransformation kinetics and implications for the fate in surface waters.

PMID- 29574649
TI  - Enhanced effect of EDDS and hydroxylamine on Fe(II)-catalyzed SPC system for
      trichloroethylene degradation.
AB  - This study presents a performance comparison of Fe(II)-catalyzed sodium
      percarbonate (SPC), Fe(II)-EDDS-catalyzed SPC, and of the innovative
      hydroxylamine hydrochloride (HA)-Fe(II)-EDDS-catalyzed SPC for the degradation of
      trichloroethylene (TCE) in water. TCE degradation was greater in the Fe(II)-EDDS
      catalyzed SPC system compared to the Fe(II)-catalyzed SPC system, indicating the
      effectiveness of adding EDDS as an enhancement factor for the removal of TCE.
      Moreover, TCE degradation was faster in the HA-Fe(II)-EDDS-catalyzed SPC system
      compared to the Fe(II)-EDDS-catalyzed SPC system, illustrating that HA can play a
      synergistic role in TCE degradation. Analysis of iron distribution in the three
      systems demonstrated that EDDS addition maintained iron in soluble form, and that
      the generation of soluble ferrous from ferric iron was expedited with addition of
      HA. Studies using nitrobenzene and carbon tetrachloride probes provided insights
      on the generation of hydroxyl radical (HO*) and superoxide anion radical (O2*-)
      in the three systems. A gradual increasing contribution of O2*- to TCE removal in
      Fe(II)-catalyzed SPC, Fe(II)-EDDS-catalyzed SPC, and HA-Fe(II)-EDDS-catalyzed SPC
      systems was verified through free-radical scavenger tests. Finally, monitoring of
      Cl- concentrations manifested the complete dechlorination of TCE. A possible
      mechanism of TCE degradation involving two pathways of HO* oxidation and O2*-
      reaction was proposed.

PMID- 29574650
TI  - Suitable flow pattern increases the removal efficiency of nitrogen in gravity
      sewers: a suitable anoxic and aerobic environment in biofilms.
AB  - The sewers have the function of carbon removal, which has been proven. But if the
      effect of nitrogen removal can be enhanced at the same time of carbon removal, it
      can lay a foundation for the realization of "sewer's working as a reactor." This
      paper investigated the effects of shear stress and C/N ratio on nitrogen removal
      through biofilms on the sewer inner wall and nitrogen transfer. The main
      conclusions are as follows: (1) nitrogen could be partially removed in sewers
      after a series of reactions; (2) the anaerobic, anoxic, aerobic environment and
      some bacteria related to nitrogen metabolism, which exist in the biofilm, promote
      the nitrification and denitrification; (3) a total of 722 functional genes
      involved in nitrogen metabolism were detected in the biofilm (C/N ratio of 10,
      shear stress of 1.4 Pa), accounting for 0.67% of all genes, and the functional
      genes related to denitrification were dominant. Graphical abstract ?.

PMID- 29574652
TI  - Extracorporeal life support for immune reconstitution inflammatory syndrome in
      HIV patients with Pneumocystis jirovecii pneumonia.
AB  - Patients with immunosuppression from human immunodeficiency virus (HIV) have been
      traditionally considered poor candidates for extracorporeal membrane oxygenation
      (ECMO) because of high in-hospital mortality and poor long-term survival. Highly
      active antiretroviral therapy (HAART) has improved survival rates in compliant
      HIV patients and reversible severe respiratory failure may warrant ECMO in this
      group. Immune reconstitution inflammatory syndrome (IRIS) involves excessive
      inflammatory response to a pathogen with paradoxical clinical deterioration
      following HAART initiation and may present as severe respiratory failure.
      Patients with IRIS supported on ECMO have been infrequently reported in
      literature. We report two HIV-positive patients who developed acute respiratory
      distress syndrome from IRIS necessitating successful veno-venous ECMO as salvage
      therapy.

PMID- 29574651
TI  - D-dimer predicts postoperative recurrence and prognosis in patients with liver
      metastasis of colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is common, and its incidence is increasing
      throughout the world. The liver is a major metastatic site, and colorectal liver
      metastasis (CRLM) has a poor prognosis. Although liver resection is the most
      effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic
      markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been
      shown to be related to colorectal tumor progression, and is also associated with
      malignant progression and recurrence in various cancers. Therefore, we evaluated
      the value of D-dimer in predicting the prognosis in CRLM. METHODS: We
      retrospectively evaluated 90 cases of resected CRLM to determine the correlation
      between D-dimer and patient survival. The cut-off value for D-dimer levels was
      determined using receiver operating characteristic curve analysis. RESULTS:
      Significant differences occurred in the recurrence group with higher D-dimer
      levels (P = 0.00736*), while the optimal cut-off value was 0.6 ug/mL. High D
      dimer levels (>= 0.6 ug/mL) were associated with poor recurrence-free survival
      (RFS; P = 0.0000841*) and cancer-specific survival (CSS; P = 0.00615*). In the
      multivariate analysis, D-dimer correlated with CRLM prognosis and independently
      predicted RFS (P = 0.0179*). CONCLUSION: High D-dimer levels were associated with
      poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore,
      D-dimer may help predict recurrence and prognosis in patients with CRLM.

PMID- 29574653
TI  - Effect of Soluble Epoxide Hydrolase in Hyperoxic Acute Lung Injury in Mice.
AB  - Hyperoxic acute lung injury is a serious complication of oxygen therapy that
      causes high mortality. Inhibition of soluble epoxide hydrolase (sEH) has been
      reported to have protective effect on lipopolysaccharide-induced acute lung
      injury (ALI). This study investigates whether sEH plays any role in the
      pathogenesis of hyperoxic ALI. Wild-type and sEH gene knockout (sEH-/-) mice were
      exposed to 100% O2 for 72 h to induce hyperoxic ALI. Hyperoxia caused
      infiltration of inflammatory cells, elevation of interleukin-1beta and
      interleukin-6 levels, and deterioration of alveolar capillary protein leak as
      well as wet/dry weight ratio in the lung. The hyperoxia-induced pulmonary
      inflammation and edema were markedly improved in sEH-/- mice. Survival rate was
      significantly improved in sEH-/- mice compared with that in wild-type mice.
      Moreover, the levels of epoxyeicosatrienoic acids and heme oxygenase-1 activity
      were notably elevated in sEH-/- mice compared with those in wild-type mice after
      exposure to 100% O2 for 72 h. The nucleotide-binding domains and leucine-rich
      repeat pyrin domains containing 3 (NLRP3) inflammasome activation and caspase-1
      activity induced by hyperoxia were inhibited in sEH-/- mice compared with those
      in wild-type mice. Inhibition of sEH by an inhibitor, AUDA, dampened hyperoxia
      induced ALI. sEH plays a vital role in hyperoxic ALI and is a potential
      therapeutic target for ALI.

PMID- 29574654
TI  - SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.
AB  - Signaling via estrogen receptors (ER) is recognized as an essential part of the
      immune regulation, and ER-mediated signaling is involved in autoimmune reactions.
      Especially ERalpha activation in immune cells has been suggested to skew cytokine
      production toward Th2/M2-type mediators, which can have protective effect on
      inflammatory diseases and reduce Th1 and Th17 responses. These effects are caused
      by increased alternative activation of macrophages and changes in the activation
      of different T cell populations. In humans, hormonal status has been shown to
      have a major impact on several inflammatory diseases. Selective estrogen receptor
      modulators (SERMs) are ER ligands that regulate ER actions in a tissue-specific
      manner mostly lacking the adverse effects of steroid hormones. The impact of
      SERMs on the immune system is less studied, but it is suggested that certain
      SERMs may also produce immunoprotective effects. Here, we show that two novel
      SERMs and raloxifene affect immune cells by promoting M2 macrophage phenotype,
      alleviating NFkappaB activity, inhibiting T cell proliferation, and stimulating
      the production of anti-inflammatory compounds such as IL10 and IL1 receptor
      antagonist. Thus, these compounds have high potency as drug candidates against
      autoimmune diseases.

PMID- 29574655
TI  - Musculoskeletal infections caused by Aerococcus urinae: a case-based review.
AB  - Aerococcus are Gram-positive bacteria that have been historically misidentified
      using standard techniques. We report a case of a 63-year-old man with septic
      oligoarthritis caused by Aerococcus urinae (isolated in two ankle synovial fluid
      cultures and in two blood cultures). Due to the lack of evidence found in a
      search performed to identify similar cases, a systematic review was conducted
      with the objective to identify and analyze all documented cases of
      musculoskeletal infections caused by Aerococcus urinae. A total of 8 cases were
      selected: 6 spondylodiscitis, 1 periarticular hip abscess, and 1 prosthetic hip
      infection. Similarly, as in other Aerococcus urinae invasive infections, these
      were presented predominantly in older males with history of urinary tract
      disease, being identified mostly by sequencing of the 16S rRNA or by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS), with an increasing incidence in the last years and generally with good
      sensitivity to beta-lactams (aminoglycosides were associated in some cases due to
      its synergistic effect). Additionally, 4 cases of musculoskeletal infections
      caused by Aerococcus viridans and 4 cases of Aerococcus urinae with ammoniacal
      and pervasive malodorous urine were identified; the last was a symptom also
      present in our case. In this review, we identify a recent increase of
      musculoskeletal infections caused by Aerococcus urinae, which as well as in
      series of other invasive infections could be well correlated with an increasing
      use of more sensible diagnosis methods in clinical laboratories. Therefore, we
      suggest that these probably will be more frequently diagnosed in the future.

PMID- 29574656
TI  - Differences in Type I interferon response in human lung epithelial cells infected
      by highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses.
AB  - Influenza A virus infection induces type I interferons (IFNs alpha/beta) which
      activate host antiviral responses through a cascade of IFN signaling events.
      Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian
      influenza viruses isolated from India, for their replication kinetics and ability
      to induce IFN-beta and interferon-stimulating genes (ISGs). The H5N1 virus showed
      a higher replication rate and induced less IFN-beta and ISGs compared to the
      H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the
      generation of differential innate immune responses during infection by these
      viruses. The non-structural 1 (NS1) protein, a major IFN-antagonist, known to
      help the virus in evading host innate immune response was compared from both the
      strains using bioinformatics tools. Analyses revealed differences in the
      composition of the NS1 proteins from the two strains that may have an impact on
      the modulation of the innate immune response. Intriguingly, H5N1 virus attenuated
      IFN-beta response in a non-NS1 manner, suggesting the possible involvement of
      other viral proteins (PB2, PA, PB1/PB1-F2) of H5N1 in synergy with NS1.
      Preliminary analyses of the above proteins of the two strains by sequence
      comparison show differences in charged residues. The insight gained will be
      useful in designing experimental studies to elucidate a probable role of the
      polymerase protein(s) in association with NS1 in inhibiting the IFN signaling and
      understanding the molecular mechanism governing the difference.

PMID- 29574657
TI  - Shallow groundwater quality and associated non-cancer health risk in agricultural
      areas (Poyang Lake basin, China).
AB  - Owing to their accessibility, shallow groundwater is an essential source of
      drinking water in rural areas while usually being used without control by
      authorities. At the same time, this type of water resource is one of the most
      vulnerable to pollution, especially in regions with extensive agricultural
      activity. These factors increase the probability of adverse health effects in the
      population as a result of the consumption of shallow groundwater. In the present
      research, shallow groundwater quality in the agricultural areas of Poyang Lake
      basin was assessed according to world and national standards for drinking water
      quality. To evaluate non-cancer health risk from drinking groundwater, the hazard
      quotient from exposure to individual chemicals and hazard index from exposure to
      multiple chemicals were applied. It was found that, in shallow groundwater, the
      concentrations of 11 components (NO3-, NH4+, Fe, Mn, As, Al, rare NO2-, Se, Hg,
      Tl and Pb) exceed the limits referenced in the standards for drinking water.
      According to the health risk assessment, only five components (NO3-, Fe, As, rare
      NO2- and Mn) likely provoke non-cancer effects. The attempt to evaluate the
      spatial distribution of human health risk from exposure to multiple chemicals
      shows that the most vulnerable area is associated with territory characterised by
      low altitude where reducing or near-neutral conditions are formed (lower reaches
      of Xiushui and Ganjiang Rivers). The largest health risk is associated with the
      immune system and adverse dermal effects.

PMID- 29574658
TI  - Colloid mobilization and heavy metal transport in the sampling of soil solution
      from Duckum soil in South Korea.
AB  - Colloid mobilization is a significant process governing colloid-associated
      transport of heavy metals in subsurface environments. It has been studied for the
      last three decades to understand this process. However, colloid mobilization and
      heavy metal transport in soil solutions have rarely been studied using soils in
      South Korea. We investigated the colloid mobilization in a variety of flow rates
      during sampling soil solutions in sand columns. The colloid concentrations were
      increased at low flow rates and in saturated regimes. Colloid concentrations
      increased 1000-fold higher at pH 9.2 than at pH 7.3 in the absence of 10 mM NaCl
      solution. In addition, those were fourfold higher in the absence than in the
      presence of the NaCl solution at pH 9.2. It was suggested that the mobility of
      colloids should be enhanced in porous media under the basic conditions and the
      low ionic strength. In real field soils, the concentrations of As, Cr, and Pb in
      soil solutions increased with the increase in colloid concentrations at initial
      momentarily changed soil water pressure, whereas the concentrations of Cd, Cu,
      Fe, Ni, Al, and Co lagged behind the colloid release. Therefore, physicochemical
      changes and heavy metal characteristics have important implications for colloid
      facilitated transport during sampling soil solutions.

PMID- 29574659
TI  - The 5alpha-Reductase Inhibitor Finasteride Exerts Neuroprotection Against
      Ischemic Brain Injury in Aged Male Rats.
AB  - Progesterone (P4) exerts potent neuroprotection both in young and aged animal
      models of stroke. The neuroprotection is likely to be mediated by
      allopregnanolone (ALLO) metabolized from P4 by 5alpha-reductase, since the
      neuroprotection is attenuated by the 5alpha-reductase inhibitor finasteride,
      which was done only with young animals though. Thus, we do not know the
      contribution of ALLO to the P4-induced neuroprotection in aged animals. We
      examined effects of finasteride on the P4-induced neuroprotection in aged (16-18
      month-old) male rats subjected to transient focal cerebral ischemia. Transient
      focal cerebral ischemia was induced by left middle cerebral artery occlusion
      (MCAO) and occlusion of the bilateral common carotid arteries. MCAO rats were
      given an 8 mg/kg P4 6 h after MCAO followed by the same treatment once a day for
      successive 3 days. Finasteride, a 5alpha-reductase inhibitor, at 20 mg/kg was
      intraperitoneally injected 30 min prior to the P4-injections. P4 markedly reduced
      neuronal damage 72 h after MCAO, and the P4-induced neuroprotection was
      apparently suppressed by finasteride in the aged animals. However, post-ischemic
      administration of finasteride alone (20 mg/kg) significantly prevented neuronal
      damage and the impairment of Rotarod performance after MCAO in aged male rats,
      but not in young ones. The androgen receptor antagonist flutamide markedly
      suppressed the neuroprotection of finasteride in the cerebral cortex, but not in
      the striatum, suggesting the androgen receptor-dependent mechanism of the
      finasteride-induced neuroprotection in the cerebral cortex. Our findings
      suggested, for the first time, the potential of finasteride as a therapeutic
      agent in post-ischemic treatment of strokes in aged population.

PMID- 29574661
TI  - A meta-analysis of consanguinity and breast cancer.
AB  - BACKGROUND: There have been various publications stating that consanguinity both
      increases and decreases the risk of breast cancer. AIMS: The objective of this
      study was to determine the impact of consanguinity upon breast cancer. We
      conducted a systematic review of the literature and meta-analysis. METHODS:
      Eligible studies were identified on Medline and EMBASE updated to the 19 of
      September 2017. Studies with sufficient comparative data were included in a meta
      analysis. Analyses were carried out using RevMan software. RESULTS: Three
      comparative studies with a total of 317 individuals with breast cancer and 1459
      controls. Reviewing the literature demonstrated conflicting conclusions of the
      influence of consanguinity upon breast cancer. The meta-analysis showed that
      there were no statistically significant associations between consanguinity and
      breast cancer though there was a trend protection from a history of
      consanguinity. CONCLUSION: Though there is limited literature published on the
      effects of parental consanguinity, the available data does not demonstrate that
      it is a risk factor for breast cancer.

PMID- 29574660
TI  - Site, trigger, quenching mechanism and recovery of non-photochemical quenching in
      cyanobacteria: recent updates.
AB  - Cyanobacteria exhibit a novel form of non-photochemical quenching (NPQ) at the
      level of the phycobilisome. NPQ is a process that protects photosystem II (PSII)
      from possible highlight-induced photo-damage. Although significant advancement
      has been made in understanding the NPQ, there are still some missing details.
      This critical review focuses on how the orange carotenoid protein (OCP) and its
      partner fluorescence recovery protein (FRP) control the extent of quenching. What
      is and what is not known about the NPQ is discussed under four subtitles; where
      does exactly the site of quenching lie? (site), how is the quenching being
      triggered? (trigger), molecular mechanism of quenching (quenching) and recovery
      from quenching. Finally, a recent working model of NPQ, consistent with recent
      findings, is been described.

PMID- 29574662
TI  - Evaluation of regulatory T lymphocytes and IL2Ra and FOXP3 gene expression in
      peripheral mononuclear cells from patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND: Loss of neuroprotective role of CD4+ helper T cells, regulatory T
      cells, and M2 microglia constitutively results in the rapid neural death in the
      "rapidly progressive phase" of amyotrophic lateral sclerosis (ALS). AIM: We aimed
      to investigate relative count of CD4+ and regulatory T lymphocytes and expression
      level of IL2Ra and FOXP3 genes in peripheral blood mononuclear cells (PBMCs) from
      patients with ALS. METHOD: We performed a flow cytometric analysis on PBMC from
      38 patients with ALS and 32 controls to determine the count of CD4+ and CD4+CD25+
      cells. Quantitative real-time PCR analyses were implemented to determine the
      level of expression of FOXP3 and IL-2Ralpha (CD25) genes in the peripheral blood
      mononucleated cells. RESULTS: We found a significant higher proportion of CD4+ T
      cells (p value < 0.001), along with a significantly reduced proportion of
      CD4+CD25+ Treg cells (p value = 0.001, p value = 0.02), in the peripheral blood
      of patient's with ALS. CONCLUSION: The results of our study are in line with the
      hypothesis that in the early phase of ALS, neuroprotective helper T cells
      infiltrate in the affected areas in the lumbar spinal cord. This was reflected in
      higher peripheral percentage of CD4+ helper T cells and higher expression of
      FOXP3 and IL-2Ralpha. The observed demise in the number of active CD4+CD25+
      regulatory T cells might indicate early signs of progression to later stages of
      ALS in our study group. Interestingly, disease duration was the sole independent
      significant determining factor that predicted CD4+CD25+ regulatory T cell counts
      in the peripheral blood of patients at various stages of ALS, according to a
      logistic regression model.

PMID- 29574663
TI  - Assessment of Protein Prenylation Pathway in Multiple Sclerosis Patients.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disorder with several genetic
      and environmental factors being implicated in its pathogenesis. Protein
      prenylation as one of the important posttranslational modifications of proteins
      has crucial role in immune system regulation. In the current case-control study,
      we compared expression of five genes coding for the different subunits of
      proteins implicated in protein prenylation in 50 Iranian MS patients with those
      of healthy subjects. No significant difference has been found in FNTA and PGGT1B
      expressions between cases and controls. Spearman correlation analysis between
      FNTA relative expression and disease duration showed significant correlation in
      male patients (r = - 0.671, P = 0.024) but not female patients (r = 0.253, P =
      0.12). FNTB expression was significantly higher in MS patients compared with
      healthy subjects. Spearman correlation analysis between FNTB relative expression
      and disease duration showed significant correlation in male patients (r = -0.876,
      P = 0.004) but not female patients (r = 0.296, P = 0.06). RABGGTA was
      significantly upregulated in total MS patients, total male patients, female
      patients aged between 30 and 40 and male patients aged >40 compared with
      corresponding control groups. RABGGTB was significantly downregulated in total MS
      patients, total female patients, and female patients aged > 40 compared with
      corresponding control groups. Totally, we demonstrated dysregulation of protein
      prenylation pathway in MS patients compared with healthy subjects. Future studies
      are needed to find the clinical implication of this pathway in MS patients.

PMID- 29574664
TI  - Wnt3a Ectopic Expression Interferes Axonal Projection and Motor Neuron
      Positioning During the Chicken Spinal Cord Development.
AB  - The formation of dorsal-ventral axis of the spinal cord is controlled largely by
      dorsal signals such as Wnts (which are members of the wingless + MMTV integrants,
      Int family), besides ventral signals such as sonic hedgehog (Shh). Wnt3a, one of
      the Wnt family members, is involved in multiple cellular functions, including
      self-renewal, proliferation, differentiation, and motility. Here, we aim to study
      the mechanism of the regulation of chicken spinal cord patterning by Wnt3a. In
      this study, Wnt3a was ectopically expressed in the spinal cord of developing
      chicken embryos by in ovo electroporation. The results of immunofluorescent
      staining revealed that Wnt3a ectopic expression caused the abnormality of
      commissural axonal projection and the formation of nerve fibers was interrupted.
      It is worth noting that neurons in the ventricular zone, especially motor
      neurons, could not migrate laterally after the Wnt3a overexpression, which led to
      the malformation of motor column. In addition, we found that neurons could not
      protrude axons outwardly after overexpression of Wnt3a in the spinal cord. It was
      also found that Wnt3a overexpression inhibited the outgrowth of processes in
      culturing SH-SY5Y cells. In conclusion, we proposed that Wnt3a regulates neuronal
      morphology, which subsequently disrupts axonal projection and motor neuron
      positioning during spinal cord development.

PMID- 29574665
TI  - Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and
      Exaggerated?
AB  - Blood pressure responses to graded exercise testing can provide important
      diagnostic and prognostic information. While published guidelines outline what
      constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response
      to exercise testing, the widespread use of exaggerated blood pressure responses
      as a clinical tool is limited due to sparse and inconsistent data. A review of
      the original sources from these guidelines reveals an overall lack of empirical
      evidence to support both the normal blood pressure responses and their upper
      limits. In this current opinion, we critically evaluate the current exercise
      blood pressure guidelines including (1) the normal blood pressure responses to
      graded exercise testing; (2) the upper limits of this normal response; (3) the
      blood pressure criteria for test termination; and (4) the thresholds for
      exaggerated blood pressure responses. We provide evidence that exercise blood
      pressure responses vary according to subject characteristics, and subsequently a
      re-evaluation of what constitutes normal and abnormal responses is necessary to
      strengthen the clinical utility of this assessment.

PMID- 29574666
TI  - Impact of increasing treatment rates on cost-effectiveness of subcutaneous
      immunotherapy (SCIT) in respiratory allergy: a decision analytic modelling
      approach.
AB  - BACKGROUND: Specific immunotherapy is the only causal treatment in respiratory
      allergy. Due to high treatment cost and possible severe side effects subcutaneous
      immunotherapy (SCIT) is not indicated in all patients. Nevertheless, reported
      treatment rates seem to be low. This study aims to analyze the effects of
      increasing treatment rates of SCIT in respiratory allergy in terms of costs and
      quality-adjusted life years (QALYs). METHODS: A state-transition Markov model
      simulates the course of disease of patients with allergic rhinitis, allergic
      asthma and both diseases over 10 years including a symptom-free state and death.
      Treatment comprises symptomatic pharmacotherapy alone or combined with SCIT. The
      model compares two strategies of increased and status quo treatment rates.
      Transition probabilities are based on routine data. Costs are calculated from the
      societal perspective applying German unit costs to literature-derived resource
      consumption. QALYs are determined by translating the mean change in non
      preference-based quality of life scores to a change in utility. Key parameters
      are subjected to deterministic sensitivity analyses. RESULTS: Increasing
      treatment rates is a cost-effective strategy with an incremental cost
      effectiveness ratio (ICER) of 3484?/QALY compared to the status quo. The most
      influential parameters are SCIT discontinuation rates, treatment effects on the
      transition probabilities and cost of SCIT. Across all parameter variations, the
      best case leads to dominance of increased treatment rates while the worst case
      ICER is 34,315?/QALY. Excluding indirect cost leads to a twofold increase in the
      ICER. CONCLUSIONS: Measures to increase SCIT initiation rates should be
      implemented and also address improving adherence.

PMID- 29574668
TI  - Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer's
      Disease.
AB  - Here we demonstrate for the first time that cannabidiol (CBD) acts to protect
      synaptic plasticity in an in vitro model of Alzheimer's disease (AD). The non
      psycho active component of Cannabis sativa, CBD has previously been shown to
      protect against the neurotoxic effects of beta amyloid peptide (Abeta) in cell
      culture and cognitive behavioural models of neurodegeneration. Hippocampal long
      term potentiation (LTP) is an activity dependent increase in synaptic efficacy
      often used to study cellular mechanisms related to memory. Here we show that
      acute application of soluble oligomeric beta amyloid peptide (Abeta1-42)
      associated with AD, attenuates LTP in the CA1 region of hippocampal slices from
      C57Bl/6 mice. Application of CBD alone did not alter LTP, however pre-treatment
      of slices with CBD rescued the Abeta1-42 mediated deficit in LTP. We found that
      the neuroprotective effects of CBD were not reversed by WAY100635, ZM241385 or
      AM251, demonstrating a lack of involvement of 5HT1A, adenosine (A2A) or
      Cannabinoid type 1 (CB1) receptors respectively. However in the presence of the
      PPARgamma antagonist GW9662 the neuroprotective effect of CBD was prevented. Our
      data suggests that this major component of Cannabis sativa, which lacks
      psychoactivity may have therapeutic potential for the treatment of AD.

PMID- 29574667
TI  - Chronic Swimming Exercise Ameliorates Low-Soybean-Oil Diet-Induced Spatial Memory
      Impairment by Enhancing BDNF-Mediated Synaptic Potentiation in Developing
      Spontaneously Hypertensive Rats.
AB  - Exercise and low-fat diets are common lifestyle modifications used for the
      treatment of hypertension besides drug therapy. However, unrestrained low-fat
      diets may result in deficiencies of low-unsaturated fatty acids and carry
      contingent risks of delaying neurodevelopment. While aerobic exercise shows
      positive neuroprotective effects, it is still unclear whether exercise could
      alleviate the impairment of neurodevelopment that may be induced by certain low
      fat diets. In this research, developing spontaneously hypertensive rats (SHR)
      were treated with chronic swimming exercise and/or a low-soybean-oil diet for 6
      weeks. We found that performance in the Morris water maze was reduced and long
      term potentiation in the hippocampus was suppressed by the diet, while a
      combination treatment of exercise and diet alleviated the impairment induced by
      the specific low-fat diet. Moreover, the combination treatment effectively
      increased the expression of brain-derived neurotrophic factor (BDNF) and N-methyl
      D-aspartic acid receptor (NMDAR), which were both down-regulated by the low
      soybean-oil diet in the hippocampus of developing SHR. These findings suggest
      that chronic swimming exercise can ameliorate the low-soybean-oil diet-induced
      learning and memory impairment in developing SHR through the up-regulation of
      BDNF and NMDAR expression.

PMID- 29574669
TI  - Microglia Polarization and Endoplasmic Reticulum Stress in Chronic Social Defeat
      Stress Induced Depression Mouse.
AB  - Inflammation recently has been considered to be participated in the pathogenesis
      of major depressive disorder (MDD). However, the detailed mechanism of
      inflammation in depression has not been completely understood yet. In the present
      study, depression mice model was established by chronic social defeat stress
      (CSDS) method and confirmed by behavior examinations including forced swimming
      test and sucrose preference test. The decrease of spine density and postsynaptic
      density protein 95 (PSD95) in hippocampus further verified the depression model.
      Then, the microglia polarization state and endoplasmic reticulum (ER) stress were
      investigated. At transcriptional level, M1 marker (inducible nitric oxide
      synthase (iNOS), CD16, CD86, CXCL10) in CSDS mice was higher than that in control
      group while there was no difference in M2 marker (Arginase and CD206) between two
      groups. And it was observed in the hippocampus of CSDS induced depression mice
      that increased activated microglia was merged with iNOS instead of arginase by
      immunofluorescence staining. Furthermore, the M1 marker Interleukin (IL)-1beta
      and tumor necrosis factor (TNF)-alpha were increased in depression mice while the
      M1 marker IL-6 and M2 marker IL-10 remained unchanged. The expression of ER
      stress signaling factors, including protein kinase RNA-like ER kinase (PERK),
      Phosphorylated alpha-subunit of eukaryotic translation initiation factor 2(p
      eIF2alpha), C/EBP homologous protein (CHOP), and X-box binding protein 1(XBP1)
      were significantly higher in CSDS-induced depression mice than in control mice.
      In all, our results suggest that M1 polarization and ER stress play a vital role
      in MDD pathogenesis.

PMID- 29574671
TI  - Impact of Prenatal and Postnatal Treatment of Sodium Fluoride and Aluminum
      Chloride on Some Hormonal and Sensorimotor Aspects in Rats.
AB  - In most communities, there is a constant exposure to environmental pollutants
      with probable negative impact on the development of the nervous system. Among
      these pollutants are the sodium fluoride (NaF) and aluminum chloride (AlCl3)
      which may represent a real threat to the proper functioning of the brain. This
      study comprises two fundamentally different strategies; in the first one,
      pregnant rats were administered a daily dose of NaF (0.15 g /L) or AlCl3 (500
      mg/L) in the drinking water either separately or in combination with each other
      from day 6 of gestation until just after weaning. In the second approach, the
      male rats born to mothers exposed to the pollutants were divided into two groups.
      In the first, rats were continued to be treated with the same pollutants
      administered to them in the drinking water at the same dose level until the age
      of 70 days. The rats of the second group were supplied with drinking water
      without either one of the pollutants for a similar period of time. The rats
      exposed to NaF separately or in combination with AlCl3 during the prenatal life
      and subsequently through the postnatal stages exhibited disturbance in the
      locomotor activities. This was concomitant with alterations in plasma, PTH, ACTH,
      and estradiol levels. Additionally, the serum levels of LH and testosterone were
      altered in the two groups treated with sodium fluoride during the prenatal and up
      to the weaning periods or in the group which continued to have the NaF until day
      70 after birth.

PMID- 29574670
TI  - Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in
      Experimental Autoimmune Encephalomyelitis.
AB  - Kv1.3 is a voltage gated potassium channel that has been implicated in
      pathophysiology of multiple sclerosis (MS). In the present study we investigated
      temporal and cellular expression pattern of this channel in the lumbar part of
      spinal cords of animals with experimental autoimmune encephalomyelitis (EAE),
      animal model of MS. EAE was actively induced in female Dark Agouti rats.
      Expression of Kv1.3 was analyzed at different time points of disease progression,
      at the onset, peak and end of EAE. We here show that Kv1.3 increased by several
      folds at the peak of EAE at both gene and protein level. Double
      immunofluorescence analyses demonstrated localization of Kv1.3 on activated
      microglia, macrophages, and reactive astrocytes around inflammatory lesions. In
      vitro experiments showed that pharmacological block of Kv1.3 in activated
      astrocytes suppresses the expression of proinflammatory mediators, suggesting a
      role of this channel in inflammation. Our results support the hypothesis that
      Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the
      list of cells whose activation would be suppressed by inhibiting Kv1.3 in
      inflammatory conditions.

PMID- 29574672
TI  - Speciation Analysis of Trace Mercury in Sea Cucumber Species of Apostichopus
      japonicus Using High-Performance Liquid Chromatography Conjunction With
      Inductively Coupled Plasma Mass Spectrometry.
AB  - In this paper, a simple and cost-effective method using high-performance liquid
      chromatography in conjunction with inductively coupled plasma mass spectrometry
      with a rapid ultrasound-assisted extraction was used for analysis speciation of
      trace mercury in sea cucumber species of Apostichopus japonicus. The effective
      separation of inorganic mercury, methylmercury, and ethylmercury was achieved
      within 10 min using Agilent ZORBAX SB-C18 analytical and guard columns with an
      isocratic mobile phase consisting of 8% methanol and 92% H2O containing 0.12% L
      cysteine (m/v) and 0.01 mol/L ammonium acetate. Mercury species were extracted
      from A. japonicus samples using a solution containing 2-mercaptoethanol, L
      cysteine, and hydrochloric acid and sonicating for 0.5 h. The limits of detection
      of inorganic mercury, methylmercury, and ethylmercury were 0.12, 0.08, and 0.20
      MUg/L, and the minimum detectable concentrations (measured at 0.500 g sample
      volume in 10.00 mL) were 2.4, 1.6, and 4.0 MUg/kg, respectively. Analysis of a
      scallop certified reference material (GBW 10024) revealed accordance between the
      experimental and certified values. This study provides a reference for the
      evaluation of mercury speciation in sea cucumber and other seafood.

PMID- 29574673
TI  - The Association Between Renal Tubular Dysfunction and Zinc Level in a Chinese
      Population Environmentally Exposed to Cadmium.
AB  - Studies in vivo and in vitro have shown a protective effect of zinc against renal
      dysfunction caused by cadmium exposure. However, limited human data is available.
      In this study, we evaluated the association between renal tubular dysfunction and
      body zinc burden in a Chinese population exposed to cadmium. A total of 331
      subjects (170 women and 161 men) living in control and cadmium-polluted area were
      included. Blood cadmium (BCd), urinary cadmium (UCd), serum zinc (SZn), zinc in
      hair (HZn), Zn/Cd ratio, and urinary beta2Microglobulin (UBMG) were measured. The
      median UCd, BCd, SZn, and HZn were 2.8 and 13.6 MUg/g cr, 1.3 and 12.2 MUg/L,
      1.31 and 1.12 mg/L, and 0.14 and 0.12 mg/g in subjects living in control and
      polluted areas. The UBMG level of subjects living in the polluted area was
      significantly higher than that of the control (0.27 vs 0.11 mg/g cr, p < 0.01).
      SZn, HZn, and Zn/Cd ratios were negatively correlated with UBMG (p < 0.05 or
      0.01). Subjects with high SZn concentrations (>= 1.62 mg/L) had reduced risks of
      elevated UBMG [(odds ratio (OR) = 0.26, 95% confidence interval (CI) 0.07-0.99)]
      after controlling for multiple covariates compared with those with lower zinc
      levels. A similar result was observed in subjects with high HZn (OR = 0.09, 95%
      CI 0.02-0.48). The ORs of the second, third, and fourth quartiles of Zn/Cd ratio
      were 0.40 (95% CI 0.19-0.84), 0.14 (95% CI 0.06-0.37), and 0.01 (95% CI 0.02
      0.18) for renal dysfunction compared with those of the first quartile,
      respectively. For those subjects with high level of UCd, high level of SZn and
      HZn also had reduced risks of elevated UBMG. The results of the present study
      show that high zinc body burden is associated with a decrease risk of renal
      tubular dysfunction induced by cadmium. Zinc nutritional status should be
      considered in evaluating cadmium-induced renal damage.

PMID- 29574674
TI  - Preventive Parenting Interventions: Advancing Conceptualizations of Participation
      and Enhancing Reach.

PMID- 29574675
TI  - Warfarin-related nephropathy with acute kidney injury in a patient with
      immunoglobulin A nephropathy.
AB  - A 55-year-old man with Marfan syndrome taking warfarin for anticoagulant therapy
      after aortic valve replacement developed acute kidney injury (serum creatinine
      level of 9.01 mg/dL) and gross macrohematuria. Renal biopsy showed red cell casts
      in the renal tubules, glomerular crescent formation in the glomeruli with
      immunoglobulin A deposition, and global sclerosis. Based on these findings, the
      patient was diagnosed with warfarin-related nephropathy with acute kidney injury
      characterized by immunoglobulin A nephropathy with crescents. The warfarin was
      withdrawn, and his hematuria and renal function improved without
      immunosuppressive agents.

PMID- 29574676
TI  - Ischemic Stroke Risk in Medicare Beneficiaries with Central Retinal Artery
      Occlusion: A Retrospective Cohort Study.
AB  - INTRODUCTION: To determine the incidence of ischemic cerebral stroke in the 6
      month periods preceding and following acute central retinal artery occlusion
      (CRAO) among Medicare beneficiaries. METHODS: A retrospective cohort study with
      comparison group conducted for calendar year 2013. Patients with CRAO were
      identified through National Medicare limited inpatient and institutional
      outpatient datasets for emergency services using ICD-9-CM code for CRAO (362.31).
      Patients with hip fractures (ICD-9-CM 820-820.9) during the same time period
      served as controls. Interval incident rates of ischemic stroke were determined
      from time-coded diagnoses of CRAO and hip fracture (index date zero) to date of
      principal discharge diagnosis of ischemic stroke (ICD-9-CM 434) recorded in the
      Medicare inpatient dataset. Risk of stroke was examined by comparing incidence
      among the two cohorts preceding and following the sentinel events. RESULTS: There
      were 3338 patients with CRAOs during 2013. The incidence of ischemic stroke
      peaked the second week following CRAO relative to patients with hip fracture
      (relative incidence = 33.1 [95% confidence interval 9.8-84.6]). CONCLUSIONS:
      Medicare beneficiaries who present to emergency rooms with CRAO or are
      hospitalized directly for this condition were at highest risk of ischemic stroke
      in the first 2 weeks following the ocular diagnosis. Patients with acute CRAO
      should be promptly evaluated for stroke and stroke prevention.

PMID- 29574678
TI  - Obstetric synthetic oxytocin use and subsequent hyperactivity/inattention
      problems in Danish children.
AB  - INTRODUCTION: The objective was to examine the association between obstetric
      synthetic oxytocin use and hyperactivity/inattention problems in offspring.
      MATERIAL AND METHODS: We identified children born in 2000-2003, enrolled in the
      Danish National Birth Cohort, with data on the Strengths and Difficulties
      Questionnaire (SDQ) reported by parents at age seven (n = 33 896) and age 11 (n =
      27 561) and the children themselves around age 11 (n = 27 251). Information on
      oxytocin administration was provided in the Medical Birth Register. We estimated
      mean differences and odds ratios for childhood hyperactivity/inattention problems
      according to oxytocin exposure. RESULTS: Synthetic oxytocin was administered in
      26% of the deliveries. We did not find the use of synthetic oxytocin during birth
      to be associated with childhood hyperactivity/inattention problems, whether
      analyzed in linear or logistic regression models. CONCLUSIONS: Our findings do
      not support any effects of obstetric use of synthetic oxytocin on
      hyperactivity/inattention problems in children when measured with the SDQ
      subscale at 7 or 11 years of age.

PMID- 29574677
TI  - An Integrated Socio-Environmental Model of Health and Well-Being: a Conceptual
      Framework Exploring the Joint Contribution of Environmental and Social Exposures
      to Health and Disease Over the Life Span.
AB  - PURPOSE OF THE REVIEW: Environmental and social determinants of health often co
      occur, particularly among socially disadvantaged populations, yet because they
      are usually studied separately, their joint effects on health are likely
      underestimated. Building on converging bodies of literature, we delineate a
      conceptual framework to address these issues. RECENT FINDINGS: Previous models
      provided a foundation for study in this area, and generated research pointing to
      additional important issues. These include a stronger focus on biobehavioral
      pathways, both positive and adverse health outcomes, and intergenerational
      effects. To accommodate the expanded set of issues, we put forward the Integrated
      Socio-Environmental Model of Health and Well-Being (ISEM), which examines how
      social and environmental factors combine and potentially interact, via multi
      factorial pathways, to affect health and well-being over the life span. We then
      provide applied examples including the study of how food environments affect
      dietary behavior. The ISEM provides a comprehensive, theoretically informed
      framework to guide future research on the joint contribution of social and
      environmental factors to health and well-being across the life span.

PMID- 29574679
TI  - In silico characterization of functional single nucleotide polymorphisms of
      folate pathway genes.
AB  - Folate metabolism genes are pivotal to critical biological processes and are
      related to several conditions, including developmental, cognitive, and
      cardiovascular anomalies. A systematic catalog of genetic polymorphisms in
      protein coding regions, regulatory transcription factor binding sites, and miRNA
      binding sites associated with folate pathway genes may contribute to personalized
      medicine. We performed a comprehensive computational survey of single nucleotide
      polymorphisms (SNPs) of folate pathway genes to highlight functional
      polymorphisms in the coding region, transcription factor binding sites, and
      miRNAs binding sites. Folate pathway genes were searched through PubMed and Kyoto
      Encyclopedia of Genes and Genomes pathway databases. SNPs were identified and
      characterized using the University of California, Santa Cruz genome browser and
      SNPnexus tool. Functional characterization of nonsynonymous SNPs (nsSNPS) was
      performed using bioinformatics tools, and common deleterious nsSNPs were
      identified. We identified 48 genes of folate pathway containing 287 SNPs in the
      coding regions. Out of these SNPs, rs5742905, rs45511401, and rs1801133 were
      predicted to be deleterious through four different bioinformatics tools. Three
      dimensional structures of two proteins with and without deleterious nsSNPs were
      predicted by SWISSPDB viewer and SuperPose. Besides, a total of 237 SNPs was
      identified in transcription factor binding sites using the Genomatix software
      suite and six miRNA target site SNPs using miRNASNP. This systematic and
      extensive in silico analysis of functional SNPs of folate pathway may provide a
      foundation for future targeted mechanistic, structure-function, and genetic
      epidemiological studies.

PMID- 29574680
TI  - Quality of both parents' cognitive guidance and quantity of early childhood
      education: Influences on pre-mathematical development.
AB  - BACKGROUND: Only a handful of longitudinal studies have explored the effects of
      both parents in early parenthood on children's cognitive development, and no
      study has controlled for simultaneous early childhood education and care (ECEC)
      experiences. AIMS: To examine the similarity of each parent's cognitive guidance
      and contribution to children's pre-mathematical outcomes across parent gender
      while controlling for amount of ECEC. SAMPLE: A longitudinal study on 66 Finnish
      two-parent families and their children. METHODS: Both parents' autonomy support
      and scaffolding behaviour were observed during play interactions with the child
      at 2;0. Children's numerical and spatial skills were tested at 3;0 and 4;0.
      Parental reports on amount of ECEC in months were collected at 2;0, 3;0, and 4;0.
      RESULTS: The two parenting constructs were conceptually similar across parent
      gender as demonstrated by fairly strong measurement equivalence. While mothers on
      average showed more scaffolding and equal amounts of autonomy support compared to
      fathers during play interaction, they displayed less variability in the former
      and more variability in the latter behaviour. The contribution of mothers' and
      fathers' cognitive guidance was more similar for children's numerical than
      spatial development. Both parents' education positively predicted autonomy
      support but not amount of ECEC exposure, which was positively related to
      numerical development. As expected, parents' education did not predict ECEC
      exposure, and child gender was not related to child outcomes. CONCLUSIONS: The
      findings are discussed in relation to measurement invariance and gender-neutral
      parenting in the context of early childhood.

PMID- 29574681
TI  - Effect of goal-directed haemodynamic therapy in free flap reconstruction for head
      and neck cancer.
AB  - BACKGROUND: In free flap reconstruction for head and neck cancer, achieving a
      haemodynamic target using excessive fluid infusion is associated with decreased
      flap survival rates and extended hospital stays. We hypothesized that goal
      directed haemodynamic therapy would improve flap survival rates and shorten
      hospitalization periods. METHODS: Patients scheduled for free flap reconstruction
      were randomly assigned to a goal-directed haemodynamic therapy group (n = 31) or
      a conventional haemodynamic therapy control group (n = 31). The control group
      received extra bolus fluid and ephedrine or norepinephrine to maintain a mean
      arterial pressure >= 65 mmHg. The goal-directed haemodynamic therapy group
      received a colloid solution as the extra bolus fluid to maintain a stroke volume
      variation < 12%; dobutamine, ephedrine, or norepinephrine was administered to
      maintain a cardiac index >= 2.5 l/min/m2 and mean arterial pressure >= 65 mmHg.
      Enhanced recovery after surgery protocols were not used except for fluid therapy.
      An otolaryngologist blinded to group assignments assessed flap outcomes and
      classified them as 'survival,' 'at risk' or 'failure.' RESULTS: The
      hospitalization period was not significantly different between the groups. The
      goal-directed haemodynamic therapy group had significantly shorter intensive care
      unit stays and a higher flap survival rate. The crystalloid volume was
      significantly lower in goal-directed haemodynamic therapy group. Reoperation
      rates, post-operative complications, and laboratory data including inflammatory
      markers were similar between the groups. CONCLUSION: Compared to conventional
      haemodynamic therapy, goal-directed haemodynamic therapy does not reduce
      hospitalization periods; it may, however, reduce the length of intensive care
      unit stays and increase flap survival rates. Further studies including multi
      centre trials with larger sample sizes are warranted.

PMID- 29574682
TI  - Human hepatocytes and cytochrome P450-selective inhibitors predict variability in
      human drug exposure more accurately than human recombinant P450s.
AB  - BACKGROUND AND PURPOSE: Drugs metabolically eliminated by several enzymes are
      less vulnerable to variable compound exposure in patients due to drug-drug
      interactions (DDI) or if a polymorphic enzyme is involved in their elimination.
      Therefore, it is vital in drug discovery to accurately and efficiently estimate
      and optimize the metabolic elimination profile. EXPERIMENTAL APPROACH: CYP3A
      and/or CYP2D6 substrates with well described variability in vivo in humans due to
      CYP3A DDI and CYP2D6 polymorphism were selected for assessment of fraction
      metabolized by each enzyme (fmCYP ) in two in vitro systems: (i) human
      recombinant P450s (hrP450s) and (ii) human hepatocytes combined with selective
      P450 inhibitors. Increases in compound exposure in poor versus extensive CYP2D6
      metabolizers and by the strong CYP3A inhibitor ketoconazole were mathematically
      modelled and predicted changes in exposure were compared with in vivo data. KEY
      RESULTS: Predicted changes in exposure were within twofold of reported in vivo
      values using fmCYP estimated in human hepatocytes and there was a strong linear
      correlation between predicted and observed changes in exposure (r2  = 0.83 for
      CYP3A, r2  = 0.82 for CYP2D6). Predictions using fmCYP in hrP450s were not as
      accurate (r2  = 0.55 for CYP3A, r2  = 0.20 for CYP2D6). CONCLUSIONS AND
      IMPLICATIONS: The results suggest that variability in human drug exposure due to
      DDI and enzyme polymorphism can be accurately predicted using fmCYP from human
      hepatocytes and CYP-selective inhibitors. This approach can be efficiently
      applied in drug discovery to aid optimization of candidate drugs with a
      favourable metabolic elimination profile and limited variability in patients.

PMID- 29574683
TI  - Topical application of corticosteroids to tracheal tubes to prevent postoperative
      sore throat in adults undergoing tracheal intubation: a systematic review and
      meta-analysis.
AB  - Postoperative sore throat negatively affects patient satisfaction and recovery.
      Numerous randomised trials have tested the efficacy of corticosteroids applied to
      tracheal tubes to prevent postoperative sore throat. We searched PubMed, EMBASE,
      the Cochrane Central Register of Controlled Trials, Wanfang Database, and the
      China Academic Journal Network Publishing Database from inception to 7 December
      2017. We included randomised controlled trials that assessed the efficacy and
      safety of corticosteroids applied to tracheal tubes, compared either with non
      analgesic controls and analgesic agents, in adults undergoing elective surgery
      under general anaesthesia. We pooled the data using a random-effects model and
      assessed the risk of random error by applying trial sequential analysis. Our
      primary outcomes were postoperative sore throat 24 h after surgery/extubation,
      and adverse events. The evidence was assessed using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) criteria. We
      included 20 randomised controlled trials involving 2200 patients. Compared with
      non-analgesic controls, corticosteroids applied to tracheal tubes were associated
      with a reduced incidence of postoperative sore throat, risk ratio (95%CI) 0.39
      (0.32-0.49) (18 trials, 1506 patients). Two randomised trials reported no adverse
      events. Compared with lidocaine, corticosteroids applied to tracheal tubes were
      associated with reduced incidence of postoperative sore throat, risk ratio
      (95%CI) 0.42 (0.35-0.51) (nine trials, 706 patients). Trial sequential analyses
      suggested the presence of firm evidence that corticosteroids applied to tracheal
      tubes were superior both to non-analgesic controls and lidocaine, in preventing
      postoperative sore throat. Evidence for postoperative sore throat for both
      comparisons was assessed as high quality. Only two trials sought adverse events;
      none were recorded.

PMID- 29574685
TI  - A prospective study of the hypertriglyceridemic waist phenotype and risk of
      incident ischemic stroke in a Chinese rural population.
AB  - OBJECTIVES: The hypertriglyceridemic waist phenotype has been reported as a
      practical tool to screen people with an increased risk of coronary artery disease
      and type 2 diabetes. The aim of this study was to investigate the relationship
      between the phenotype and ischemic stroke in a rural population in south China.
      MATERIALS AND METHODS: A total of 4081 participants aged over 35 years old
      without a stroke history were surveyed in 2009 and followed up from May 2014 to
      January 2016. The hypertriglyceridemic waist phenotype was defined as a waist
      circumference >=90 cm and a triglyceride level >=2.0 mmol/L in males, and a waist
      circumference >=85 cm and a triglyceride level >=1.5 mmol/L in females. A Cox
      regression model was used to estimate the association of the phenotype and
      ischemic stroke. RESULTS: After a mean of 5.16 years of follow-up, 138
      individuals developed ischemic stroke. The hypertriglyceridemic waist phenotype
      was significantly associated with an increased risk of ischemic stroke before and
      after adjustment for confounding factors; the hazard ratios and 95% confidence
      intervals were 1.94 (1.27-2.96) and 1.71 (1.05-2.78), respectively. Further
      stratified analysis confirmed the associations in females (2.37 [1.09-5.14]) and
      smokers (3.20 [1.30-7.92]). A significant association of the phenotype and
      ischemic stroke risk was observed in subjects with normal glucose levels (2.94
      [1.58-5.47]) but not in subjects with impaired fasting glucose and diabetes.
      CONCLUSIONS: The hypertriglyceridemic waist phenotype is associated with an
      increased risk of ischemic stroke and might be a simple tool to screen
      individuals with a high risk for ischemic stroke.

PMID- 29574684
TI  - Associations Between Polypharmacy and Cognitive and Physical Capability: A
      British Birth Cohort Study.
AB  - OBJECTIVES: To investigate longitudinal associations between polypharmacy and
      cognitive and physical capability and to determine whether these associations
      differ with cumulative exposure to polypharmacy. DESIGN: Prospective birth cohort
      study. SETTING: England, Scotland, and Wales. PARTICIPANTS: An eligible sample of
      men and women from the Medical Research Council National Survey of Health and
      Development with medication data at age 69 (N=2,122, 79%). MEASUREMENTS:
      Cognitive capability was assessed using a word learning test, visual search speed
      task, and the Addenbrooke's Cognitive Examination, Third Edition (ACE-III).
      Physical capability was measured using chair rise speed, standing balance time,
      walking speed, and grip strength. RESULTS: Polypharmacy (5-8 prescribed
      medications) was present in 18.2% of participants at age 69 and excessive
      polypharmacy (>=9 prescribed medications) in 4.7%. Both were associated with
      poorer cognitive and physical capability in models adjusted for sex, education,
      and disease burden. Stronger associations were found for excessive polypharmacy
      (e.g., difference in mean ACE-III scores comparing polypharmacy=-2.0, 95% CI=-2.8
      to -1.1 and excessive polypharmacy=-2.9, 95% CI=-4.4 to -1.4 with no
      polypharmacy). Participants with polypharmacy at age 60 to 64 and at age 69
      showed stronger Negative associations with cognitive and physical capability were
      stronger still in participants with polypharmacy at both age 60 to 64 and at age
      69 (e.g. difference in mean chair rise speed, comparing polypharmacy with no
      polypharmacy at both ages=-3.9, 95% CI=-5.2 to -2.6 and at age 60-64 only=-2.5,
      95% CI=-4.1 to -0.9). CONCLUSION: Polypharmacy at age 60 to 64 and age 69 was
      associated with poorer physical and cognitive capability, even after adjusting
      for disease burden. Stronger negative associations were seen in participants with
      longstanding polypharmacy, suggesting a cumulative, dose-dependent relationship
      (where dose is the number of prescribed medications). Future research aiming to
      improve cognitive and physical capability should consider interventions to reduce
      the duration and level of polypharmacy at younger ages, in addition to optimizing
      disease control with appropriate medications.

PMID- 29574686
TI  - Brassicales phylogeny inferred from 72 plastid genes: A reanalysis of the
      phylogenetic localization of two paleopolyploid events and origin of novel
      chemical defenses.
AB  - PREMISE OF THE STUDY: Previous phylogenetic studies employing molecular markers
      have yielded various insights into the evolutionary history across Brassicales,
      but many relationships between families remain poorly supported or unresolved. A
      recent phylotranscriptomic approach utilizing 1155 nuclear markers obtained
      robust estimates for relationships among 14 of 17 families. Here we report a
      complete family-level phylogeny estimated using the plastid genome. METHODS: We
      conducted phylogenetic analyses on a concatenated data set comprising 44,926 bp
      from 72 plastid genes for species distributed across all 17 families. Our
      analysis includes three additional families, Tovariaceae, Salvadoraceae, and
      Setchellanthaceae, that were omitted in the previous phylotranscriptomic study.
      KEY RESULTS: Our phylogenetic analyses obtained fully resolved and strongly
      supported estimates for all nodes across Brassicales. Importantly, these findings
      are congruent with the topology reported in the phylotranscriptomic study. This
      consistency suggests that future studies could utilize plastid genomes as markers
      for resolving relationships within some notoriously difficult clades across
      Brassicales. We used this new phylogenetic framework to verify the placement of
      the At-alpha event near the origin of Brassicaceae, with median date estimates of
      31.8 to 42.8 million years ago and restrict the At-beta event to one of two nodes
      with median date estimates between 85 to 92.2 million years ago. These events
      ultimately gave rise to novel chemical defenses and are associated with
      subsequent shifts in net diversification rates. CONCLUSIONS: We anticipate that
      these findings will aid future comparative evolutionary studies across
      Brassicales, including selecting candidates for whole-genome sequencing projects.

PMID- 29574687
TI  - Effect of low-dose bortezomib on bone formation in smouldering multiple myeloma.

PMID- 29574688
TI  - Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute
      Malnutrition.
AB  - Infants and young children with severe acute malnutrition (SAM) are treated with
      empiric broad-spectrum antimicrobials. Parenteral ceftriaxone is currently a
      second-line agent for invasive infection. Oral metronidazole principally targets
      small intestinal bacterial overgrowth. Children with SAM may have altered drug
      absorption, distribution, metabolism, and elimination. Population
      pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of
      recommending optimal dosing. Eighty-one patients with SAM (aged 2-45 months)
      provided 234 postdose pharmacokinetic samples for total ceftriaxone,
      metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also
      measured in 190 of these samples. A three-compartment model adequately described
      free ceftriaxone, with a Michaelis-Menten model for concentration and albumin
      dependent protein binding. A one-compartment model was used for both
      metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole
      predicted to be formed during first-pass. Simulations showed 80 mg/kg once daily
      of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to
      reach therapeutic targets.

PMID- 29574689
TI  - Targeting glial cannabinoid CB2 receptors to delay the progression of the
      pathological phenotype in TDP-43 (A315T) transgenic mice, a model of amyotrophic
      lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: Cannabinoid CB2 receptors are up-regulated in reactive
      microglia in the spinal cord of TDP-43 (A315T) transgenic mice, an experimental
      model of amyotrophic lateral sclerosis. To determine whether this up-regulation
      can be exploited pharmacologically, we investigated the effects of different
      treatments that affect CB2 receptor function. EXPERIMENTAL APPROACH: We treated
      TDP-43 (A315T) transgenic mice with the non-selective agonist WIN55,212-2, alone
      or combined with selective CB1 or CB2 antagonists, as well as with the selective
      CB2 agonist HU-308, and evaluated their effects on the pathological phenotype.
      KEY RESULTS: WIN55,212-2 had modest beneficial effects in the rotarod test, Nissl
      staining of motor neurons, and GFAP and Iba-1 immunostainings in the spinal cord,
      which were mediated in part by CB2 receptor activation. HU-308 significantly
      improved the rotarod performance of the transgenic mice, with complete
      preservation of Nissl-stained motor neurons in the ventral horn. Reactive
      astrogliosis labelled with GFAP was also attenuated by HU-308 in the dorsal and
      ventral horns, in which CB2 receptors colocalize with this astroglial marker.
      Furthermore, HU-308 reduced the elevated Iba-1 immunostaining in the ventral horn
      of TDP-43 transgenic mice, but did not affect this immunoreactivity in white
      matter, in which CB2 receptors also colocalize with this microglial marker.
      CONCLUSIONS AND IMPLICATIONS: Our study shows an important role for glial CB2
      receptors in limiting the progression of the pathological phenotype in TDP-43
      (A315T) transgenic mice. Such benefits appear to derive from the activation of
      CB2 receptors concentrated in astrocytes and reactive microglia located in spinal
      dorsal and ventral horns.

PMID- 29574690
TI  - Our Buddies, Ourselves: The Role of Sexual Homophily in Adolescent Friendship
      Networks.
AB  - The present study tests the assumption that peers wield sufficient influence to
      induce sexual homophily (i.e., similarities in sexual experiences). Because girls
      face greater stigma for their sexual experiences than do boys, sexual homophily
      may be greater in girls' friendship networks than in boys'. Stochastic actor
      based models were used to analyze network data (n = 2,566; ages 14-18) from two
      high schools in the National Longitudinal Study of Adolescent to Adult Health.
      Sexual homophily was present in friendship networks. Girls and boys were equally
      susceptible to their friends' influence, but the former exhibited a stronger
      preference for befriending same sexual debut status peers than the latter. The
      findings suggest that adolescents-particularly girls-"curate" their networks to
      minimize peer ostracism.

PMID- 29574691
TI  - Rapid plasticity attenuation soon after birth revealed by habituation in newborn
      chicks.
AB  - Habituation reflects a form of experience-dependent plasticity whereby the
      organism progressively learns to ignore the irrelevant information repeatedly
      encountered. Here, we measured the freezing response to a repeated loud noise in
      three groups of newborn chicks (Gallus gallus) of different ages (1-2 Day old, 2
      3 Day old, and 3-4 Day old) to investigate the ontogeny of habituation in this
      avian species. Habituation was already present 1 Day after hatching, revealing
      that the neural mechanisms underlying this form of plasticity are immediately
      active. Unexpectedly, however, we also found that in the second Day of
      stimulation the amount of learning was significantly attenuated in chicks of 3-4
      days of age as compared to the younger animals, thus showing that 24-48 hr of
      maturation were sufficient to reduce plasticity. While previous findings in other
      animal species have proved the existence of a precocious critical period of
      plasticity in early cortical areas by means of sensory deprivation, our results
      demonstrate that during the initial development of an intact avian brain also the
      degree of plasticity underlying a learning process like habituation is maximal
      soon after birth, and then is subject to a rapid attenuation.

PMID- 29574692
TI  - P2Y12 receptor modulation of ADP-evoked intracellular Ca2+ signalling in THP-1
      human monocytic cells.
AB  - BACKGROUND AND PURPOSE: The Gi -coupled, ADP-activated P2Y12 receptor is well
      characterized as playing a key role in platelet activation via crosstalk with the
      P2Y1 receptor in ADP-evoked intracellular Ca2+ responses. However, there is
      limited knowledge on the role of P2Y12 receptors in ADP-evoked Ca2+ responses in
      other blood cells. Here, we investigated the role of P2Y12 receptor activation in
      the modulation of ADP-evoked Ca2+ responses in human THP-1 monocytic cells.
      EXPERIMENTAL APPROACH: A combination of intracellular Ca2+ measurements, RT-PCR,
      immunocytochemistry, leukocyte isolation and siRNA-mediated gene knockdown were
      used to identify the role of P2Y12 receptor activation. KEY RESULTS: ADP-evoked
      intracellular Ca2+ responses (EC50 2.7 MUM) in THP-1 cells were abolished by
      inhibition of PLC (U73122) or sarco/endoplasmic reticulum Ca2+ -ATPase
      (thapsigargin). Loss of ADP-evoked Ca2+ responses following treatment with
      MRS2578 (IC50 200 nM) revealed a major role for P2Y6 receptors in mediating ADP
      evoked Ca2+ responses. ADP-evoked responses were attenuated either with pertussis
      toxin treatment, or P2Y12 receptor inhibition with two chemically distinct
      antagonists (ticagrelor, IC50 5.3 MUM; PSB-0739, IC50 5.6 MUM). ADP-evoked
      responses were suppressed following siRNA-mediated P2Y12 gene knockdown. The
      inhibitory effects of P2Y12 antagonists were fully reversed following adenylate
      cyclase inhibition (SQ22536). P2Y12 receptor expression was confirmed in freshly
      isolated human CD14+ monocytes. CONCLUSIONS AND IMPLICATIONS: Taken together,
      these data suggest that P2Y12 receptor activation positively regulates P2Y6
      receptor-mediated intracellular Ca2+ signalling through suppression of adenylate
      cyclase activity in human monocytic cells.

PMID- 29574693
TI  - Physiologically Based Pharmacokinetic Modeling to Identify Physiological and
      Molecular Characteristics Driving Variability in Drug Exposure.
AB  - Prospectively defining the physiological and molecular characteristics most
      likely driving between-subject variability (BSV) in drug exposure provides the
      opportunity to inform the assessment of biomarkers to account for this
      variability. A physiologically based pharmacokinetic (PBPK) model was constructed
      and verified for dabrafenib. This model was then used to evaluate the
      physiological and molecular characteristics driving BSV in dabrafenib exposure.
      The capacity to discriminate a steady-state dabrafenib trough concentration >48
      ng/mL was also evaluated. The mean simulated/observed ratios for the parameters
      describing dabrafenib exposure in single-dose, multiple-dose, and drug-drug
      interaction studies were between 0.78 and 1.23. Multivariable analysis indicated
      that consideration of baseline weight, body mass index, and CYP2C8, CYP3A4, and P
      gp abundance strongly predicts steady-state dabrafenib trough concentration above
      48 ng/mL (ROC AUC = 0.94; accuracy = 86%). This is the first study to use a
      verified PBPK model to identify baseline physiological and molecular
      characteristics driving BSV in drug exposure.

PMID- 29574694
TI  - Comparing Meta-analysis and Individual Person Data Analysis Using Raw Data on
      Children's Understanding of Equivalence.
AB  - A prevailing theory of mathematical problem solving predicts that children will
      be less accurate solving a + b = c + __ problems versus a + b = __ + c. However,
      this has never been tested directly. Because of low base rates, information
      combined from multiple studies can help improve estimation accuracy and
      precision. This study compared meta-analysis and individual person data (IPD)
      analysis using raw data from 14 studies (N = 1,414; ns = 30-232; Mage reported =
      8;7). Substantive results challenge the prevailing theory. Methodological results
      demonstrate the advantages of using meta-analysis and IPD over single-study
      analysis. Moreover, IPD can be more powerful than meta-regression for detecting
      between-study moderation effects.

PMID- 29574695
TI  - Children and young people's understanding of inherited conditions and their
      attitudes towards genetic testing: A systematic review.
AB  - Children and young people are increasingly likely to receive information
      regarding inherited health risks relevant to their genetic relatives and
      themselves. We reviewed the literature to determine what children and young
      people (21 years and younger) understand about inherited conditions and their
      attitudes towards genetic testing. We screened 1815 abstracts to identify 20
      studies representing the perspectives of 1811 children and young people between
      the ages of 6 and 21 years (1498 children or young people at general population
      level risk from 9 studies, 313 affected/at risk from 15 studies). Children and
      young people at general population-level risk demonstrated a basic understanding
      that disease predisposition can be inherited within families. Those affected by
      or at risk of genetic conditions inferred their genetic status from observable,
      relational characteristics within their family and the results of personal
      genetic testing if it had occurred, but some misunderstandings of important
      genetic concepts were evident. Children and young people expressed interest in
      and a willingness to undertake personal genetic testing, but also articulated
      concerns about the limitations and risks of testing. Paediatric patients require
      developmentally-sensitive genetic counselling and support in navigating the
      unique landscape of their condition.

PMID- 29574696
TI  - The Gait Outcomes Assessment List (GOAL): a new tool to assess cerebral palsy.

PMID- 29574697
TI  - Parallel fabrication of macroporous scaffolds.
AB  - Scaffolds generated from naturally occurring and synthetic polymers have been
      investigated in several applications because of their biocompatibility and
      tunable chemo-mechanical properties. Existing methods for generation of 3D
      polymeric scaffolds typically cannot be parallelized, suffer from low
      throughputs, and do not allow for quick and easy removal of the fragile
      structures that are formed. Current molds used in hydrogel and scaffold
      fabrication using solvent casting and porogen leaching are often single-use and
      do not facilitate 3D scaffold formation in parallel. Here, we describe a simple
      device and related approaches for the parallel fabrication of macroporous
      scaffolds. This approach was employed for the generation of macroporous and non
      macroporous materials in parallel, in higher throughput and allowed for easy
      retrieval of these 3D scaffolds once formed. In addition, macroporous scaffolds
      with interconnected as well as non-interconnected pores were generated, and the
      versatility of this approach was employed for the generation of 3D scaffolds from
      diverse materials including an aminoglycoside-derived cationic hydrogel
      ("Amikagel"), poly(lactic-co-glycolic acid) or PLGA, and collagen. Macroporous
      scaffolds generated using the device were investigated for plasmid DNA binding
      and cell loading, indicating the use of this approach for developing materials
      for different applications in biotechnology. Our results demonstrate that the
      device-based approach is a simple technology for generating scaffolds in
      parallel, which can enhance the toolbox of current fabrication techniques.

PMID- 29574698
TI  - Biphasic effects of THC in memory and cognition.
AB  - A generally undesired effect of cannabis smoking is a reversible disruption of
      short-term memory induced by delta-9-tetrahydrocannabinol (THC), the primary
      psychoactive component of cannabis. However, this paradigm has been recently
      challenged by a group of scientists who have shown that THC is also able to
      improve neurological function in old animals when chronically administered at low
      concentrations. Moreover, recent studies demonstrated that THC paradoxically
      promotes hippocampal neurogenesis, prevents neurodegenerative processes occurring
      in animal models of Alzheimer's disease, protects from inflammation-induced
      cognitive damage and restores memory and cognitive function in old mice. With the
      aim to reconcile these seemingly contradictory facts, this work will show that
      such paradox can be explained within the framework of hormesis, defined as a
      biphasic dose-response.

PMID- 29574699
TI  - Editorial.

PMID- 29574700
TI  - Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori-
      and cancer-associated DNA methylome changes.
AB  - The large geographic variations in the incidence of gastric cancer (GC) are
      likely due to differential environmental exposures, in particular to Helicobacter
      pylori (H. pylori) infection. We aimed to investigate the impact of H. pylori on
      the epigenome in normal gastric mucosa and methylation changes associated with
      cancer risk independent of H. pylori. A discovery set of normal gastric mucosa
      from GC cases (n = 42) and controls (n = 42), nested in a large case-control
      study and stratified by H. pylori status, were subjected to genome-wide
      methylation profiling. Single-nucleotide polymorphism arrays from peripheral
      blood leukocytes were used to conduct methylation quantitative trait loci (mQTL)
      analysis. A validation set of gastric mucosa samples (n = 180) was used in the
      replication phase. We found 1,924 differentially methylated positions (DMPs) and
      438 differentially methylated regions (DMRs) associated with H. pylori infection,
      most of which were hypermethylated. Significant methylation alterations
      identified in the initial set were successfully replicated. Furthermore, the H.
      pylori-associated DMP/Rs showed marked stability ('epigenetic memory') after H.
      pylori clearance. Interestingly, we found 152 DMRs associated with cancer risk
      independent of the H. pylori status in normal gastric mucosa. The methylation
      score derived from three biomarkers was a strong predictor of GC. Finally, the
      mQTL analysis indicated that the H. pylori- and cancer-specific methylation
      signatures were minimally affected by genetic variation. The comprehensively
      characterized methylome changes associated with H. pylori infection and GC risk
      in our study might serve as potential biomarkers for early cancer progression in
      tumour-free gastric mucosa.

PMID- 29574701
TI  - Final safety, tolerability, and seizure outcomes in patients with focal epilepsy
      treated with adjunctive perampanel for up to 4 years in an open-label extension
      of phase III randomized trials: Study 307.
AB  - OBJECTIVE: To evaluate long-term safety/tolerability and seizure outcomes in
      patients with focal seizures treated with adjunctive perampanel in the open-label
      extension (OLEx) Study 307 (ClinicalTrials.gov identifier: NCT00735397). METHODS:
      Patients could enter the OLEx after completing one of the double-blind, phase III
      studies. Safety/tolerability and seizure outcomes (median percent reduction in
      seizure frequency per 28 days, and 50% responder and seizure freedom rates) were
      analyzed during the OLEx in cohorts with the same minimum perampanel exposure for
      all focal seizures and secondarily generalized seizures (SGS). An additional
      sensitivity analysis accounted for early dropouts from the OLEx. RESULTS: Of 1480
      patients randomized across the double-blind studies, 1218 enrolled in the OLEx.
      The majority of patients (65.4%-80.9%) received a last daily dose of perampanel
      12 mg and completed long-term assessment on the same, or one fewer, concomitant
      antiepileptic drug compared with baseline. The long-term safety/tolerability
      profile was consistent with the double-blind studies. Treatment-emergent adverse
      events (TEAEs) leading to discontinuation in >1% of patients were dizziness,
      irritability, and fatigue; TEAEs of clinical interest were stable for 4 years. In
      all cohorts, seizure outcome improvements were sustained over time. Median
      percent seizure reductions per 28 days reached 62.0% and 70.6% for patients with
      >=3 (n = 436) or >=4 (n = 78) years of exposure, respectively; corresponding 50%
      responder rates were 59.6% and 67.9%. The largest median percent seizure
      reduction per 28 days occurred in SGS for patients with SGS at baseline: 88.0%
      and 100.0% for patients with >=3 (n = 190) or >=4 (n = 28) years of exposure,
      respectively; in these cohorts 40.0% and 53.6% of patients, respectively,
      attained freedom from SGS. Median percent seizure reductions per 28 days were
      similar when early dropouts were accounted for. SIGNIFICANCE: Long-term (<=4
      years) adjunctive perampanel treatment did not raise new safety/tolerability
      signals and was associated with markedly improved seizure control, particularly
      in patients with SGS at baseline.

PMID- 29574702
TI  - Achlorophyllous orchid can utilize fungi not only for nutritional demands but
      also pollinator attraction.

PMID- 29574704
TI  - A non-canonical tumor suppressive role for the long non-coding RNA MALAT1 in
      colon and breast cancers.
AB  - Long noncoding RNAs (lncRNAs) constitute one of the largest classes of
      transcripts and have been widely implicated in various diseases such as cancer.
      Increasing evidence suggests that several lncRNAs are dysregulated and play
      critical roles in tumorigenesis. LncRNAs can be regulated by key oncogenes and
      tumor suppressors, adding complexity to the intricate crosstalk between protein
      coding genes and the noncoding transcriptome. In our study, we investigated the
      effect that dysregulation of the key tumor suppressor PTEN has on the noncoding
      transcriptome. We identified the lncRNA metastasis associated lung adenocarcinoma
      transcript 1 (MALAT1) as a target of PTEN and find that this regulation is
      conserved in both human and mouse as well as with both chronic and acute PTEN
      dysregulation. We show that this regulation is at least in part microRNA (miRNA)
      dependent, and characterize the miRNAs that may be mediating this crosstalk. In
      summary, we establish and characterize a non-canonical PTEN-microRNA-MALAT1 axis
      that regulates tumorigenesis and describe for the first time that the MALAT1
      lncRNA possesses novel tumor suppressive properties in colon and breast cancers.

PMID- 29574703
TI  - Genomic alterations in plasma DNA from patients with metastasized prostate cancer
      receiving abiraterone or enzalutamide.
AB  - In patients with metastatic castrate-resistant prostate cancer (mCRPC),
      circulating tumor DNA (ctDNA) analysis offers novel opportunities for the
      development of non-invasive biomarkers informative of treatment response with
      novel agents targeting the androgen-receptor (AR) pathway, such as abiraterone or
      enzalutamide. However, the relationship between ctDNA abundance, detectable
      somatic genomic alterations and clinical progression of mCRPC remains unexplored.
      Our study aimed to investigate changes in plasma DNA during disease progression
      and their associations with clinical variables in mCRPC patients. We analyzed
      ctDNA in two cohorts including 94 plasma samples from 25 treatment courses (23
      patients) and 334 plasma samples from 125 patients, respectively. We conducted
      whole-genome sequencing (plasma-Seq) for genome-wide profiling of somatic copy
      number alterations and targeted sequencing of 31 prostate cancer-associated
      genes. The combination of plasma-Seq with targeted AR analyses identified
      prostate cancer-related genomic alterations in 16 of 25 (64%) treatment courses
      in the first cohort, in which we demonstrated that AR amplification does not
      always correlate with poor abiraterone and enzalutamide therapy outcome. As we
      observed a wide variability of ctDNA levels, we evaluated ctDNA levels and their
      association with clinical parameters and included the second, larger cohort for
      these analyses. Employing altogether 428 longitudinal plasma samples from 148
      patients, we identified the presence of bone metastases, increased lactate
      dehydrogenase and prostate-specific antigen (PSA) as having the strongest
      association with high ctDNA levels. In summary, ctDNA alterations are observable
      in the majority of patients with mCRPC and may eventually be useful to guide
      clinical decision-making in this setting.

PMID- 29574705
TI  - A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.
AB  - OBJECTIVE: Many previous studies of drug repurposing have relied on literature
      review followed by evaluation of a limited number of candidate compounds. Here,
      we demonstrate the feasibility of a more comprehensive approach using high
      throughput screening to identify inhibitors of a gain-of-function mutation in the
      SCN8A gene associated with severe pediatric epilepsy. METHODS: We developed
      cellular models expressing wild-type or an R1872Q mutation in the Nav 1.6 sodium
      channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing
      the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel
      activation as well as delayed inactivation; both changes are consistent with a
      gain-of-function mutation. We next developed a fluorescence-based, sodium flux
      assay and used it to assess an extensive library of approved drugs, including a
      panel of antiepileptic drugs, for inhibitory activity in the mutated cell line.
      Lead candidates were evaluated in follow-on studies to generate concentration
      response curves for inhibiting sodium influx. Select compounds of clinical
      interest were evaluated by electrophysiology to further characterize drug effects
      on wild-type and mutant sodium channel functions. RESULTS: The screen identified
      90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four
      drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and
      carbamazepine-were further investigated and demonstrated concentration-dependent
      inhibition of sodium channel currents. SIGNIFICANCE: A comprehensive drug
      repurposing screen identified potential new candidates for the treatment of
      epilepsy caused by the R1872Q mutation in the SCN8A gene.

PMID- 29574706
TI  - FDA launches public education effort to prevent youth e-cigarette use: Advocacy
      group wants agency to speed up new requirements.

PMID- 29574707
TI  - Errata.

PMID- 29574708
TI  - Lung cancer screening based on personal risk may save more lives.

PMID- 29574709
TI  - Errata.

PMID- 29574710
TI  - Author response to Dickison, P. et al. 2018 Letter to the Editor re McGillis
      Hall, L. et al. 2018. Changing nurse licensing examinations: media analysis and
      implications of the Canadian experience. International Nursing Review 65, 13-23.

PMID- 29574711
TI  - An evaluation of the agreement between the conservative dual-criterion method and
      expert visual analysis.
AB  - The conservative dual-criterion (CDC) method was developed to standardize the
      analysis of single-subject experimental designs data, but to date its accuracy
      has been evaluated only by comparing results to the statistical parameters of
      graphs. Our study investigated agreement between expert visual analysts and the
      CDC method on 66 AB tiers from published multiple baseline graphs. We found
      strong agreement between the two methods for certain types of graphs and discuss
      implications of the findings and areas for future research.

PMID- 29574712
TI  - A common language of seizures and epilepsies: International League Against
      Epilepsy 2017 classifications.

PMID- 29574713
TI  - Selective percutaneous muscle lengthening in cerebral palsy: when there is little
      or no evidence.

PMID- 29574714
TI  - Paediatric convulsive status epilepticus, epilepsy, and behavioural outcomes.

PMID- 29574715
TI  - Treatment and outcome of adult-onset neuroblastoma.
AB  - Adult-onset neuroblastoma is rare and little is known about its biology and
      clinical course. There is no established therapy for adult-onset neuroblastoma.
      Anti-GD2 immunotherapy is now standard therapy in children with high-risk
      neuroblastoma; however, its use has not been reported in adults. Forty-four
      adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were
      treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had
      INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included
      somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11
      patients with locoregional disease, 10-year progression-free (PFS) and overall
      survival (OS) was 35.4 +/- 16.1% and 61.4 +/- 15.3%, respectively. Among 33
      adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after
      induction chemotherapy and/or surgery. Seven patients with primary refractory
      neuroblastoma (all with osteomedullary but no soft tissue disease) received anti
      GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were
      similar to those in children, response rate being 71.4%. In patients with stage 4
      disease at diagnosis, 5-year PFS was 9.7+/- 5.3% and most patients who were alive
      with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS
      being only 19.0 +/- 8.2%. Patients who achieved CR after induction had superior
      PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma
      appeared to have different biology from pediatric or adolescent NB, and poorer
      outcome. Complete disease control appeared to improve long-term survival. Anti
      GD2 immunotherapy was well tolerated and might be beneficial.

PMID- 29574716
TI  - Acceptability of a text message-based fertility awareness application for family
      planning in Lucknow, India.
AB  - OBJECTIVE: To assess user satisfaction and acceptability toward a cell phone
      based short message system (SMS) application for fertility awareness. METHODS:
      Between July 1 and September 30, 2013, the present observational study recruited
      women of reproductive age who were presenting for family planning services in
      Lucknow, India, who were not pregnant, agreed to use the application, and
      understood basic English. The application collected information on an
      individual's menstrual cycle and, using the calendar days approach, predicted
      fertility. Based on an algorithm, the application sent a daily SMS text
      indicating the participant's fertility status. Participants completed an
      acceptability survey at the end of the 60-day pilot period. RESULTS: There were
      21 participants enrolled. All reported that the application was highly
      acceptable, and found it to be private, secure, and convenient. All participants
      were interested in receiving future SMS reminders for tracking fertility. Most
      participants (20 [95%]) reported being likely or very likely to recommend the
      family planning application to friends. CONCLUSION: The application, with the
      aims of helping participants to identify their most fertile days once a month
      during ovulation and make informed decisions regarding fertility and
      contraception, was highly acceptable and might be useful in low-resource settings
      worldwide. Larger studies are needed for software optimization and determination
      of long-term effectiveness.

PMID- 29574717
TI  - Dynamic SAP102 expression in the hippocampal subregions of rats and APP/PS1 mice
      of various ages.
AB  - The hippocampus is a structurally and functionally complex brain area that plays
      important and diverse roles in higher brain functions, such as learning and
      memory, and mounting evidence indicates that different hippocampal subregions
      play distinctive roles. The hippocampus is also one of the first regions in the
      brain to suffer damage in Alzheimer's disease (AD). Synaptic dysfunction in the
      hippocampus, rather than neuronal loss per se, is paralleled by behavioural and
      functional deficits in AD. The membrane-associated guanylate kinase (MAGUK)
      family of proteins, including SAP102, PSD-95, PSD-93 and SAP97, have long been
      recognized as essential components of the postsynaptic density (PSD) at
      excitatory synapses. Hippocampal spines are the predominant synaptic transmission
      sites of excitatory glutamatergic synapses. During postnatal brain development,
      individual MAGUK members show distinct expression patterns. Although SAP102 has
      been confirmed as the dominant scaffold protein in neonatal synapses, its
      expression profiles in adult and ageing rodent hippocampi are discrepant.
      Furthermore, in AD brains, significantly reduced SAP102 protein levels have been
      found, suggesting that SAP102 may be related to AD progression; however, the
      precise mechanism underlying this result remains unclear. Herein, we observed
      distinct SAP102 expression profiles in the hippocampal CA1, CA3 and DG subregions
      of rats and APPswe/PS1dE9 (APP/PS1) mice at various ages using
      immunofluorescence. In Wistar rats, SAP102 was not only highly expressed in the
      hippocampal subregions of neonatal rats but also maintained relatively high
      expression levels in adult hippocampi and displayed no obvious decreases in the
      CA1 and DG subregions of aged rats. Surprisingly, we observed abnormally high
      SAP102 expression levels in the CA1 stratum moleculare and CA3 stratum
      polymorphum subregions of 2-month-old APP/PS1 mice, but low SAP102 levels in the
      DG and CA3 subregions of 7-month-old APP/PS1 mice, reflecting the subregion
      specific reactivity and vulnerability of AD mouse models in different disease
      stages. Our findings provide fundamental data to support the functional
      differences of SAP102 in different hippocampal subregions during postnatal
      periods and may serve as the basis for additional functional studies on SAP102 in
      normal physiological conditions and different stages of AD.

PMID- 29574718
TI  - Compromised regulation of the collecting duct ENaC activity in mice lacking AT1a
      receptor.
AB  - ENaC-mediated sodium reabsorption in the collecting duct (CD) is a critical
      determinant of urinary sodium excretion. Existing evidence suggest direct
      stimulatory actions of Angiotensin II (Ang II) on ENaC in the CD, independently
      of the aldosterone-mineralocorticoid receptor (MR) signaling. Deletion of the
      major renal AT1 receptor isoform, AT1a R, decreases blood pressure and reduces
      ENaC abundance despite elevated aldosterone levels. The mechanism of this
      insufficient compensation is not known. Here, we used patch clamp
      electrophysiology in freshly isolated split-opened CDs to investigate how AT1a R
      dysfunction compromises functional ENaC activity and its regulation by dietary
      salt intake. Ang II had no effect on ENaC activity in CDs from AT1a R -/- mice
      suggesting no complementary contribution of AT2 receptors. We next found that
      AT1a R deficient mice had lower ENaC activity when fed with low (<0.01% Na+ ) and
      regular (0.32% Na+ ) but not with high (~2% Na+ ) salt diet, when compared to the
      respective values obtained in Wild type (WT) animals. Inhibition of AT1 R with
      losartan in wild-type animals reproduces the effects of genetic ablation of AT1a
      R on ENaC activity arguing against contribution of developmental factors.
      Interestingly, manipulation with aldosterone-MR signaling via deoxycosterone
      acetate (DOCA) and spironolactone had much reduced influence on ENaC activity
      upon AT1a R deletion. Consistently, AT1a R -/- mice have a markedly diminished MR
      abundance in cytosol. Overall, we conclude that AT1a R deficiency elicits a
      complex inhibitory effect on ENaC activity by attenuating ENaC Po and precluding
      adequate compensation via aldosterone cascade due to decreased MR availability.

PMID- 29574719
TI  - IL-35, a hallmark of immune-regulation in cancer progression, chronic infections
      and inflammatory diseases.
AB  - Cytokine members of the IL-12 family have attracted enormous attention in the
      last few years, with IL-35 being the one of the most attractive-suppressive
      cytokine. IL-35 is an important mediator of regulatory T cell function.
      Regulatory T cells play key roles in restoring immune homeostasis after facing
      challenges such as infection by specific pathogens. Moreover, a crucial role for
      regulatory T cell populations has been demonstrated in several physiological
      processes, including establishment of fetal-maternal tolerance, maintenance of
      self-tolerance and prevention of autoimmune diseases. However, a deleterious
      involvement of immune regulatory T cells has been documented in specific
      inhibition of immune responses against tumor cells, promotion of chronic
      infections and establishment of chronic inflammatory disorders. In this review,
      we attempt to shed light on the concept of immune-homoeostasis on the
      aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The
      dilemma between immune-mediated cancer treatment and inflammation is discussed.
      Histopathological indications of chronic vs. acute infections are elaborated.
      Moreover, the evidence that IL-35 requires additional immune-regulatory
      cytokines, such as IL-10 and TGF-beta, to induce effective and maximal anti
      inflammatory effects suggest that immune-regulation requires multi-factorial
      analysis of many immune playmakers rather than a specific immune target.

PMID- 29574720
TI  - Joint problems arising from lack of repair mechanisms: can cannabinoids help?
AB  - Osteoarthritis (OA) is the most common disease of joints, which are complex
      organs where cartilage, bone and synovium cooperate to allow a range of
      movements. During progression of the disease, the function of all three main
      components is jeopardized. Nevertheless, the involvement of each tissue in OA
      development is still not established and is the topic of the present review. The
      OA therapies available are symptomatic, largely targeting pain management rather
      than disease progression. The strong need to develop a treatment for cartilage
      degeneration, bone deformation and synovial inflammation has led to research on
      the involvement of the endocannabinoid system in the development of OA. The
      current review discusses the research on this topic to date and notes the
      advantages of exploiting endocannabinoid system modulation for cartilage, bone
      and synovium homeostasis, which could prevent the further progression of OA.

PMID- 29574721
TI  - Folate deficiency inhibits the PCP pathway and alters genomic methylation levels
      during embryonic development.
AB  - Folate deficiency results in abnormal embryonic development, but the underlying
      mechanisms remain to be comprehensively investigated. Mutation of Vangl genes
      belonging to the planar cell polarity (PCP) pathway is associated with abnormal
      embryonic development, but the effect of folate deficiency on the PCP pathway is
      unclear. In this study, we found that folate deficiency inhibited Vangl gene
      expression and Vangl protein binding to the ligand Dvl. As a methyl donor, folate
      can chemically alter the DNA methylation levels of genomic sequences. Here,
      reduced representation bisulfite sequencing (RRBS) was employed to detect the
      methylation profiles of mouse embryos. The results confirmed that folate
      deficiency affected the genomic methylation levels of mouse embryos, which
      resulted in down-regulation of key genes involved in embryonic development. Gene
      ontology (GO) analysis suggested that the genes located in the differentially
      methylated regions (DMRs) are primarily involved in biological regulation,
      cellular processes, development, metabolism, and signaling pathways. The data
      revealed that folate deficiency inhibits the PCP pathway and alters genomic
      methylation profiles, which may be the underlying mechanisms through which folate
      deficiency impairs embryonic development.

PMID- 29574722
TI  - TUSC7: A novel tumor suppressor long non-coding RNA in human cancers.
AB  - Accumulating evidences has shown that tumor suppressor candidate 7 (TUSC7) as a
      putatively tumor suppressor gene in various tumors. The low-expression of TUSC7
      is related to poor prognosis, and increased the proliferation rate of tumor
      cells. Over-expression of TUSC7 could suppress tumor cell proliferation,
      migration, invasion, and colony formation, suggesting that TUSC7 might be a
      diagnostic and prognostic biomarker, as well as therapeutic target. In this
      review, we summarized the molecular mechanism and clinical significance of TUSC7
      in tumorigenesis, tumor progression, and prognosis.

PMID- 29574724
TI  - Extremely thin layer plastification for focused-ion beam scanning electron
      microscopy: an improved method to study cell surfaces and organelles of cultured
      cells.
AB  - Since the recent boost in the usage of electron microscopy in life-science
      research, there is a great need for new methods. Recently minimal resin embedding
      methods have been successfully introduced in the sample preparation for focused
      ion beam scanning electron microscopy (FIB-SEM). In these methods several
      possibilities are given to remove as much resin as possible from the surface of
      cultured cells or multicellular organisms. Here we introduce an alternative way
      in the minimal resin embedding method to remove excess of resin from two widely
      different cell types by the use of Mascotte filter paper. Our goal in correlative
      light and electron microscopic studies of immunogold-labelled breast cancer SKBR3
      cells was to visualise gold-labelled HER2 plasma membrane proteins as well as the
      intracellular structures of flat and round cells. We found a significant
      difference (p < 0.001) in the number of gold particles of selected cells per 0.6
      MUm2 cell surface: on average a flat cell contained 2.46 +/- 1.98 gold particles,
      and a round cell 5.66 +/- 2.92 gold particles. Moreover, there was a clear
      difference in the subcellular organisation of these two cells. The round SKBR3
      cell contained many organelles, such as mitochondria, Golgi and endoplasmic
      reticulum, when compared with flat SKBR3 cells. Our next goal was to visualise
      crosswall associated organelles, septal pore caps, of Rhizoctonia solani fungal
      cells by the combined use of a heavy metal staining and our extremely thin layer
      plastification (ETLP) method. At low magnifications this resulted into easily
      finding septa which appeared as bright crosswalls in the back-scattered electron
      mode in the scanning electron microscope. Then, a septum was selected for FIB
      SEM. Cross-sectioned views clearly revealed the perforate septal pore cap of R.
      solani next to other structures, such as mitochondria, endoplasmic reticulum,
      lipid bodies, dolipore septum, and the pore channel. As the ETLP method was
      applied on two widely different cell types, the use of the ETLP method will be
      beneficial to correlative studies of other cell model systems and multicellular
      organisms.

PMID- 29574725
TI  - Personal risk factors associated with burnout among psychotherapists: A
      systematic review of the literature.
AB  - OBJECTIVES: Emotionally taxing job demands place psychotherapists at risk for
      burnout, often to the detriment of the therapist, clients, and the profession of
      psychotherapy (Maslach, 2007). The aim of the present systematic review was to
      (a) explore the levels of both burnout and job stress in psychotherapists, (b)
      identify tools used to measure work-related stress and burnout, and (c) identify
      personal risk factors for developing burnout among psychotherapists. METHOD:
      Databases PsycINFO, Medline, EMBASE, ASSIA, and CINHAL were searched. Forty
      articles met inclusion criteria. RESULTS: Over half of sampled psychotherapists
      reported moderate-high levels of burnout, with the majority of results based on
      quantitative cross-sectional self-report surveys. Younger age, having less work
      experience, and being overinvolved in client problems were the most common
      personal risk factors for moderate-high levels of stress and burnout among
      psychotherapists. CONCLUSION: It appears that psychotherapists commonly
      experience some burnout, and personal factors influence burnout development.

PMID- 29574723
TI  - Calcium-dependent potassium channels control proliferation of cardiac progenitor
      cells and bone marrow-derived mesenchymal stem cells.
AB  - KEY POINTS: Ex vivo proliferated c-Kit+ endogenous cardiac progenitor cells
      (eCPCs) obtained from mouse and human cardiac tissues have been reported to
      express a wide range of functional ion channels. In contrast to previous reports
      in cultured c-Kit+ eCPCs, we found that ion currents were minimal in freshly
      isolated cells. However, inclusion of free Ca2+ intracellularly revealed a
      prominent inwardly rectifying current identified as the intermediate conductance
      Ca2+ -activated K+ current (KCa3.1) Electrical function of both c-Kit+ eCPCs and
      bone marrow-derived mesenchymal stem cells is critically governed by KCa3.1
      calcium-dependent potassium channels. Ca2+ -induced increases in KCa3.1
      conductance are necessary to optimize membrane potential during Ca2+ entry.
      Membrane hyperpolarization due to KCa3.1 activation maintains the driving force
      for Ca2+ entry that activates stem cell proliferation. Cardiac disease
      downregulates KCa3.1 channels in resident cardiac progenitor cells. Alterations
      in KCa3.1 may have pathophysiological and therapeutic significance in
      regenerative medicine. ABSTRACT: Endogenous c-Kit+ cardiac progenitor cells
      (eCPCs) and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are being
      developed for cardiac regenerative therapy, but a better understanding of their
      physiology is needed. Here, we addressed the unknown functional role of ion
      channels in freshly isolated eCPCs and expanded BM-MSCs using patch-clamp,
      microfluorometry and confocal microscopy. Isolated c-Kit+ eCPCs were purified
      from dog hearts by immunomagnetic selection. Ion currents were barely detectable
      in freshly isolated c-Kit+ eCPCs with buffering of intracellular calcium (Ca2+i
      ). Under conditions allowing free intracellular Ca2+ , freshly isolated c-Kit+
      eCPCs and ex vivo proliferated BM-MSCs showed prominent voltage-independent
      conductances that were sensitive to intermediate-conductance K+ -channel (KCa3.1
      current, IKCa3.1 ) blockers and corresponding gene (KCNN4)-expression knockdown.
      Depletion of Ca2+i induced membrane-potential (Vmem ) depolarization, while store
      operated Ca2+ entry (SOCE) hyperpolarized Vmem in both cell types. The
      hyperpolarizing SOCE effect was substantially reduced by IKCa3.1 or SOCE blockade
      (TRAM-34, 2-APB), and IKCa3.1 blockade (TRAM-34) or KCNN4-knockdown decreased the
      Ca2+ entry resulting from SOCE. IKCa3.1 suppression reduced c-Kit+ eCPC and BM
      MSC proliferation, while significantly altering the profile of cyclin expression.
      IKCa3.1 was reduced in c-Kit+ eCPCs isolated from dogs with congestive heart
      failure (CHF), along with corresponding KCNN4 mRNA. Under perforated-patch
      conditions to maintain physiological [Ca2+ ]i , c-Kit+ eCPCs from CHF dogs had
      less negative resting membrane potentials (-58 +/- 7 mV) versus c-Kit+ eCPCs from
      control dogs (-73 +/- 3 mV, P < 0.05), along with slower proliferation. Our study
      suggests that Ca2+ -induced increases in IKCa3.1 are necessary to optimize
      membrane potential during the Ca2+ entry that activates progenitor cell
      proliferation, and that alterations in KCa3.1 may have pathophysiological and
      therapeutic significance in regenerative medicine.

PMID- 29574726
TI  - Browning Index of Anthocyanin-Rich Fruit Juice Depends on pH and Anthocyanin Loss
      More Than the Gain of Soluble Polymeric Pigments.
AB  - : Browning index (BI, ABS520 nm /ABS420 nm ) is a measure of anthocyanin-rich
      fruit juice pigmentation quality. This study sought to determine the extent to
      which BI describes anthocyanin quality and degradation in fruit juices.
      Commercial fruit juices were assayed for monomeric anthocyanin (MA) content,
      percent polymeric color (%PC), pH, and BI. BI varied, 0.29 to 1.72, among
      cranberry, cherry, grape, aronia, and pomegranate juices. Principal component
      analysis (PCA) revealed that BI was strongly inversely associated with %PC, and
      positively correlated with MAs to a lesser extent. The BI of grape and cherry
      juices varied linearly with pH from 2.0 to 4.0 in pH-adjusted juices. Cherry and
      grape juices at pH approximately 2.0 to 4.0 were incubated at 50  degrees C to
      induce juice browning. BI and MA decreased, and %PC increased, but the amount of
      MA degradation was not explained by %PC. In the aged juices, BI and MA were
      strongly correlated using PCA. In aged grape juice, chromatographic analysis was
      used characterize anthocyanins, proanthocyanidins, and anthocyanin scission
      products. Anthocyanin loss and a gain of unresolved components absorbing at 420
      nm decreased BI. Proanthocyanidins and co-eluting pigments with varying BI
      decreased during aging. Scission products did not account for anthocyanin loss.
      Thus, MA loss more so than the gain in pigments associated with juice
      proanthocyanidins contribute to the increase in %PC and decline of the BI during
      accelerated aging of grape juice. Thus, BI is a useful marker of fruit juice
      quality within juices of the same pH and anthocyanin composition. PRACTICAL
      APPLICATION: Fruit juice pigmentation depends on anthocyanins, pH, and other
      matrix components. Spectrophotometric methods to determine pigmentation include
      the browning index (ABS520 nm /ABS420 nm ), pH differential method for monomeric
      anthocyanin (MA) content, and bisulfite bleaching to determine percent polymeric
      color (%PC). In this study, anthocyanin-rich fruit juice browning index was
      strongly dependent on pH and MA content. MA loss, and to a lesser extent, a gain
      in newly-formed pigments at 420 nm contributed to the browning index change
      during aging. Therefore, browning index is strongly associated with MA content
      and is useful for assessing fruit juice quality.

PMID- 29574727
TI  - Distribution of cytochrome oxidase-rich patches in human primary visual cortex.
AB  - We studied the tangential distribution of cytochrome oxidase (CytOx)-rich patches
      (blobs) in the striate cortex (V1) of normally sighted Homo sapiens. We analyzed
      the spatial density and cross-sectional area of patches in CytOx-reacted
      tangential sections of flat-mounted preparations of V1 and surrounding areas.
      CytOx-rich patches were most clearly defined in the supragranular cortical layers
      of V1, particularly at middle levels of layer III. Variations in patch spatial
      density were subtle across different visual eccentricity representations. Within
      the binocular representation of V1, the average patch spatial density decreased
      slightly with increasing cortical eccentricity, from around 1.0 patch/mm2 in the
      foveal representation to 0.6 patch/mm2 at the representation of ~60 degrees 
      eccentricity, but seemed to increase again at the representation of the monocular
      crescent. Across the entire sample, the cross-sectional area of patches (i.e.,
      patch size) varied from approximately 0.2-0.8 mm2 , with a mean value of 0.32 mm2
      . Notably, there was no significant variation in the mean patch size across
      eccentricity representations. Human patches are on average larger than those
      reported for nonhuman primate brains, and analysis of species with different
      brain sizes suggests an approximately linear relationship between V1 area and
      patch size. The relative constancy of patch metrics across eccentricities is in
      stark contrast with the exponential variation in V1 cortical magnification,
      suggesting a nearly invariant modular organization throughout human V1.

PMID- 29574728
TI  - Cross-validation of PAI scales for the detection of suspected ADHD in adults.
AB  - The purpose of this study was to cross-validate scales and subscales of the
      Personality Assessment Inventory (PAI) identified in previously published
      research against criterion variables for the identification of Attention
      Deficit/Hyperactivity Disorder (ADHD) in adults. Performance-based indicators of
      attention deficits from the Wechsler Adult Intelligence Scale-Fourth Edition were
      used as criterion variables. In a hierarchical logistic regression analysis, the
      addition of the PAI scales to the criterion variables did significantly improve
      the fit of the model, with an overall classification accuracy of 75%. Limitations
      of this study and implications for future research are discussed.

PMID- 29574730
TI  - Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap
      formation and inflammatory response-related gene expression.
AB  - BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for
      periodontitis, and smoking perturbs neutrophil reactive oxygen species
      production. This study tested the hypothesis that cigarette smoke extract (CSE)
      and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may
      influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in
      neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil
      extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as
      well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre
      treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence
      based assays. The impact of CSE and SCN- treatment on neutrophil respiratory
      burst- and inflammation-related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1,
      NCF2, CYBB) was determined by real-time polymerase chain reaction. RESULTS: Both
      CSE and SCN- pre-treatment inhibited phorbol 12-myristate-13-acetate-stimulated
      NET release. Additionally, SCN- inhibited hypochlorous acid-stimulated NET
      formation, while SCN- alone stimulated NET release. Overall, neutrophils pre
      treated with CSE exhibited reduced speed, velocity and directionality relative to
      untreated neutrophils. Although CSE and SCN- promoted DNAJB1 expression,
      increased redox-related gene expression was only detected in response to SCN-.
      CONCLUSION: These results suggest that CSE can alter ex vivo neutrophil
      activation by mechanisms independent of SCN- and nicotine, and SCN- may
      contribute to the perturbed innate immune responses observed in smokers.

PMID- 29574729
TI  - Minimally invasive versus open pancreatic enucleation. Systematic review and meta
      analysis of surgical outcomes.
AB  - Parenchymal sparing procedures are gaining interest in pancreatic surgery and
      recent studies have reported that minimally invasive pancreatic enucleation may
      be associated with enhanced outcomes when compared with traditional surgery. By
      meta-analyzing the available data from the literature, minimally invasive surgery
      is not at higher risk of pancreatic fistula and offers a number of advantages
      over conventional surgery for pancreatic enucleation.

PMID- 29574731
TI  - Commentary: A time to reap and a time to sow: reducing the adolescent suicide
      rate now and in the future: commentary on Cha et al. (2018).
AB  - Cha and colleagues have provided an erudite, lucid, and comprehensive survey of
      where research on adolescent suicide has been, and where it should go. Their
      paper provides a broad global picture of the descriptive epidemiology of
      adolescent suicide, describes environmental, psychological, social, and
      biological processes likely to be associated with suicidal risk, reviews extant
      approaches to the management of adolescent suicidal behavior, and makes
      recommendations for future research. This editorial will expand on some of their
      recommendations, and also remind readers, that, regardless of how much we still
      need to learn, we do possess knowledge that, if applied now, could help to reduce
      the adolescent suicide rate in the near term.

PMID- 29574733
TI  - Commentary: Understanding the impact of domestic violence on children,
      recognizing strengths, and promoting resilience: reflections on Harold and
      Sellers (2018).
AB  - Violence and abuse in families occurs frequently with significant impact on
      children of all ages. However, this type of interpersonal violence is often the
      least disclosed or discussed. Therefore, the Harold and Sellers paper is
      important to bring attention to the broad range of both behavioral and
      neuroscience research in this area and the clinical implications for children and
      adolescents including risk for later psychopathology. The commentary also expands
      an understanding of the impact and outcomes for very young children exposed to
      domestic violence. The authors provide a thorough description of the many
      prevention and intervention programs and approaches to help children exposed to
      domestic violence. In conclusion, it is essential to recognize that even at times
      of adversity for children and families, such as when domestic violence occurs, it
      is important to recognize strengths and support resilience.

PMID- 29574732
TI  - Commentary: Biological embedding of childhood adversity: where do we go from
      here? A reflection on Koss and Gunnar (2018).
AB  - The review by Koss & Gunna provides a scholarly overview of the role of the
      hypothalamic-pituitary-adrenal (HPA) axis in mediating the association between
      childhood adversity and psychopathology. Through their insightful observations,
      the authors craft a rich framework to critically appraise the current evidence
      and inform future research in this area. Overall, the review calls for a new
      generation of studies testing biological embedding hypotheses with greater
      attention to design, measurement, statistical models, and translational
      approaches. These new studies are much needed. By uncovering the causal pathways
      underlying the biological embedding of childhood adversity, we can gain important
      new tools to prevent the most impairing forms of psychopathology among the most
      vulnerable individuals in society.

PMID- 29574734
TI  - Commentary: The neonatal brain and the challenge of imaging biomarkers,
      reflections on Batalle et al. (2018).
AB  - This review by Batalle et al. comes at an important time in the field as neonatal
      imaging has matured to a point that important questions can now be asked in a
      more definitive way. Identifying imaging biosmarkers that reflect the prenatal
      and early childhood origins of cognitive ability, behavior, and risk for
      neuropsychiatric disorders is now possible, and this commentary offers
      suggestions for addressing some of the challenges that lie ahead.

PMID- 29574735
TI  - Commentary: Whither the epigenetics of child psychopathology? Some reflections
      provoked by Barker et al. (2018).
AB  - Barker et al.'s. () review addresses one of the most fundamental questions in the
      fields of child psychology and psychiatry - How can adverse experiences shape
      development to a sufficient degree and in profound and enduring ways to create
      long term risk for later mental disorder and disability? In particular they
      discuss the plausibility of differential methylation as an epigenetic mechanism
      by which such exposures can become neuro-biologically embedded. Our commentary
      rises six question relating to key issues that need to be addressed as we search
      for definitive evidence from human studies that such mechanisms actually do make
      an important causal contribution to abnormal trajectories of development to
      disorder.

PMID- 29574736
TI  - Commentary: Randomized controlled trials in autism spectrum disorder: state of
      the field and challenges for the future.
AB  - This issue of the Journal includes two articles summarizing the evidence from
      clinical trials aimed at improving symptoms of autism. French and Kennedy
      (Journal of Child Psychology and Psychiatry, 2018, xx, xxxx) systematically
      review randomized controlled trials (RCTs) aimed at an "early intervention" and
      focus on trials including children with or at risk of autism under age 6 years.
      Although no type of intervention were excluded from their review, none of the
      included 48 RCTs employed pharmacological modalities and the overwhelming
      majority tested psychological/behavioural interventions aimed at modifying
      aspects of observed behaviours that are abnormal in children with autism. Using
      the standard Cochrane tool for evaluating risk of bias, French and Kennedy
      conclude that many RCTs are of low quality, which throws into question the
      reliance that should be placed on the findings.

PMID- 29574737
TI  - Annual Research Review: Interparental conflict and youth psychopathology: an
      evidence review and practice focused update.
AB  - The quality of the interparental relationship is recognized as an important
      influence on child and adolescent psychopathology. Historically, clinically
      oriented research on this topic has focused on the impacts of parental divorce
      and domestic violence as primary interparental relationship influences on child
      outcomes, to the relative neglect of dimensional or qualitative features of the
      couple/interparental relationship for youth (child and adolescent)
      psychopathology. Recent research has highlighted that children are affected by
      attributes of interparental conflict, specifically how parents express and manage
      conflicts in their relationship, across a continuum of expressed severity and
      negativity - ranging from silence to violence. Furthermore, new evidence
      highlights that children's emotional, behavioral, social, academic outcomes, and
      future interpersonal relationships are adversely affected by conflict between
      parents/carers whether adults are living together or not (i.e. married or
      separated), or where children are or are not genetically related to their rearing
      parents (e.g. adoption). We review evidence and present an integrated theoretical
      model, highlighting how children are affected by interparental conflict and what
      this evidence base means for effective intervention and prevention program
      development, as well as the development of possible cost-benefit models.
      Additionally, we review policy implications of this research and highlight some
      very recent examples of UK-based policy focusing on addressing the interparental
      relationship and its impact on youth psychopathology.

PMID- 29574738
TI  - Commentary: Types of bullying, types of intervention: reflections on Arseneault
      (2018).
AB  - Arseneault's review is a timely reminder of the strong evidence for the negative
      impact of school bullying, especially although not only on the victims of it. It
      is particularly important in dealing with the evidence for causal links,
      mechanisms and possible moderating factors. In this Commentary, I raise some
      issues about the definition of bullying; the importance of separating out the
      bully/victim category; differing impacts of types of victimisation, and notably
      cyber victimization, perhaps interacting with gender; and evidence on school
      antibullying policies and impact of interventions.

PMID- 29574739
TI  - Reimagining the environment in developmental psychopathology: from molecules to
      effective interventions.
AB  - The Journal of Child Psychology and Psychiatry's Annual Research Review (ARR) is
      a must-read special issue of the journal that presents a series of major reviews
      of key topics in the field. This year the ARR consists of eight reviews, each
      accompanied by a commentary from a leading expert in the field, on a diverse
      range of topics addressing, in complementary ways, the key role of the
      environment in child psychopathology and in leveraging change in the service of
      prevention and intervention. Topics include epigenetics, stress physiology,
      neonatal imaging, interparental conflict, bullying, autism treatments and
      suicide. The papers considered together represent the very best of contemporary
      child psychology and psychiatry research.

PMID- 29574740
TI  - Annual Research Review: The state of autism intervention science: progress,
      target psychological and biological mechanisms and future prospects.
AB  - BACKGROUND: There has been recent systematic review of key evidence in
      psychosocial intervention in autism but little review of biological treatments.
      METHODS: We analyse the current literature from the perspective of intervention
      and mechanism targets across social and biological development. RESULTS: The
      overall quality of trials evidence in autism intervention remains relatively low,
      despite some recent progress. Many treatments in common use have little or no
      evidence base. This is very concerning in such an important disorder. A variety
      of psychosocial interventions can show effect to improve some short-term effects
      on children's immediate dyadic social interactions, for instance with caregivers.
      But showing true effectiveness in this developmental disorder requires
      generalisation of such effects into wider social contexts, on autism symptoms and
      in long-term progress in development. Only a few interventions so far have begun
      to show this. A number of early phase interventions on biological targets have
      shown real promise, but none has yet progressed to larger scale effectiveness
      trials on behavioural or symptom outcomes. CONCLUSIONS: There has been enough
      progress in psychosocial intervention research now to be able to begin to
      identify some evidence-based practice in autism treatment. To consolidate and
      improve outcomes, the next phase of intervention research needs improved trial
      design, and an iterative approach building on success. It may also include the
      testing of potential synergies between promising biological and psychosocial
      interventions.

PMID- 29574741
TI  - Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase
      to switch the nucleotide-cofactor specificity for increasing l-lysine production.
AB  - l-lysine is an important amino acid in animals and humans and NADPH is a vital
      cofactor for maximizing the efficiency of l-lysine fermentation.
      Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a
      variance in nucleotide-cofactor affinity in bacteria. In this study, we
      rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its
      nucleotide-cofactor specificity resulting in an increase in final titer (from
      82.6 to 117.3 g L-1 ), carbon yield (from 0.35 to 0.44 g [g glucose]-1 ) and
      productivity (from 2.07 to 2.93 g L-1  hr-1 ) of l-lysine in JL-6 DeltadapB::Ec
      dapBC115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed
      the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating
      that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production.
      Subsequently, we rationally modified the conserved structure of cofactor-binding
      motif, and results indicated that introducing the mutation K11A or R13A in
      CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the
      nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated
      DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in
      l-lysine production was observed for JL-6 DeltadapB::Ec-dapBC115G,G116C ,
      followed by JL-6 Cg-dapBC37G,G38C (21.4%) and JL-6 DeltadapB::Ec-dapBC46G,G47C
      (15.2%). This is the first report of a rational modification of DHDPR that
      enhances the l-lysine production and yield through the modulation of nucleotide
      cofactor specificity.

PMID- 29574742
TI  - Editorial: Step-Families in Family Therapy and Family Science.

PMID- 29574743
TI  - Morphological evidence for novel enteric neuronal circuitry in guinea pig distal
      colon.
AB  - The gastrointestinal (GI) tract is unique compared to all other internal organs;
      it is the only organ with its own nervous system and its own population of
      intrinsic sensory neurons, known as intrinsic primary afferent neurons (IPANs).
      How these IPANs form neuronal circuits with other functional classes of neurons
      in the enteric nervous system (ENS) is incompletely understood. We used a
      combination of light microscopy, immunohistochemistry and confocal microscopy to
      examine the topographical distribution of specific classes of neurons in the
      myenteric plexus of guinea-pig colon, including putative IPANs, with other
      classes of enteric neurons. These findings were based on immunoreactivity to the
      neuronal markers, calbindin, calretinin and nitric oxide synthase. We then
      correlated the varicose outputs formed by putative IPANs with subclasses of
      excitatory interneurons and motor neurons. We revealed that calbindin
      immunoreactive varicosities form specialized structures resembling 'baskets'
      within the majority of myenteric ganglia, which were arranged in clusters around
      calretinin-immunoreactive neurons. These calbindin baskets directly arose from
      projections of putative IPANs and represent morphological evidence of
      preferential input from sensory neurons directly to a select group of calretinin
      neurons. Our findings uncovered that these neurons are likely to be ascending
      excitatory interneurons and excitatory motor neurons. Our study reveals for the
      first time in the colon, a novel enteric neural circuit, whereby calbindin
      immunoreactive putative sensory neurons form specialized varicose structures that
      likely direct synaptic outputs to excitatory interneurons and motor neurons. This
      circuit likely forms the basis of polarized neuronal pathways underlying
      motility.

PMID- 29574745
TI  - A new method for selecting auricle positions in skull base reconstruction for
      temporal bone cancer.
AB  - OBJECTIVE: In advanced temporal bone carcinoma cases, we attempted to preserve as
      much of the auricle as possible from a cosmetic and functional perspective.
      Difficulties are associated with selecting an adequate position for reconstructed
      auricles intraoperatively. We improved the surgical procedure to achieve a good
      postoperative auricle position. METHODS: Nine patients were included in this
      study. All patients underwent subtotal removal of the temporal bone and resection
      of the external auditory canal while preserving most of the external ear, and
      lateral skull base reconstruction was performed with anterolateral thigh flaps.
      We invented a new device, the auricle localizer, to select the correct position
      for the replaced external ear. The head skin incision line and two points of
      three-point pin fixation were used as criteria, and a Kirschner wire was shaped
      as a basic line to match these criteria. Another Kirschner wire was shaped by
      wrapping it around the inferior edge of the external ear as the positioning line,
      and these two lines were then combined. To evaluate the postoperative auricle
      position, the auricle inclination angle was measured using head frontal
      cephalogram imaging. RESULTS: The external ear on the affected side clearly
      drooped postoperatively in nonlocalizer cases, whereas this was not obvious in
      localizer cases. Auricle inclination angles 1 year after surgery significantly
      differed between these two cases (P = 0.018). CONCLUSION: The surgical device,
      the auricle localizer, is useful for selecting intraoperative accurate auricle
      positions. The assessment index, the auricle inclination angle, is useful for
      quantitatively evaluating postoperative results. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2605-2610, 2018.

PMID- 29574744
TI  - Peptidoglycan induces bradykinin receptor 1 expression through Toll-like receptor
      2 and NF-kappaB signaling pathway in human nasal mucosa-derived fibroblasts of
      chronic rhinosinusitis patients.
AB  - Numerous studies have demonstrated that Gram-positive microbiomes play an
      important role in the pathogenesis and in the way of treatment of chronic
      rhinosinusitis (CRS). Kinins are inflammatory mediators and one of their
      receptors, namely bradykinin receptor 1 (BKR1 or B1R), is believed to be induced
      and involved in inflammation in pathophysiological conditions. In the present
      study, we investigated the effect of peptidoglycan (PGN), a major cell wall
      component of G(+) bacteria, on BKR expression and its signaling pathway in nasal
      fibroblasts from CRS without nasal polyp (CRSsNP). The PGN induced increases in
      B1R mRNA and protein production. The induction was abolished by the NF-kappaB and
      protein kinase A inhibitor. In parallel, the PGN treatment directly activated
      IkappaB/NF-kappaB signaling and CREB phosphorylation. Interestingly, a further
      analysis suggested no involvement of cAMP/PKA/CREB pathway in this induction. The
      B1R expression and IkappaB/NF-kappaB signaling pathway could be attenuated by
      Toll-like receptor-2 (TLR2) blocking/neutralizing Ab. In a functional assay, the
      addition of B1R selective agonist (Des-Arg10 -kallidin) to the fibroblasts after
      PGN stimulation led to an increase in CXCL8 release and p38 MAPK and ERK1/2
      phosphorylation, which could be inhibited by the B1R antagonist. Taken together,
      our results revealed for the first time that PGN can increase B1R expression in
      human nasal mucosa-derived fibroblasts through TLR2 activation and NF-kappaB
      signaling pathway. This induction functionally leads to MAPKs activation and
      CXCL8 release upon B1R stimulation. Our results also suggest that a major
      component of G(+) bacteria can participate in B1R upregulation in nasal mucosa
      during CRSsNP progression.

PMID- 29574746
TI  - Concentrates of triterpenic acids obtained from crude olive pomace oils:
      characterization and evaluation of their potential antioxidant activity.
AB  - BACKGROUND: Pentacyclic triterpenic acids (TA) are phytochemicals of increasing
      nutritional interest owing to their bioactive properties, such as anti
      inflammatory, antitumoral, antihyperglycemic and hepatoprotective. Crude olive
      pomace oils constitute a non-exploited significant source of these compounds. In
      the present study, concentrates of TA were extracted and characterized from crude
      olive pomace oils that were obtained by centrifugation and subsequent solvent
      extraction, respectively. Specifically, the concentrates were obtained from the
      byproduct generated in the filtration of the oils. The solids were subjected to
      Soxhlet extractions with hexane to remove the residual oil and then with ethanol
      for the TA extraction. RESULTS: Concentrates containing 850-980 g kg-1 TA were
      isolated from the oils obtained by centrifugation, whereas those isolated from
      oils obtained by hexane extraction presented levels of TA that ranged from 510 to
      900 g kg-1 . Oleanolic (OA) and maslinic (MA) acids were the TA found in the
      concentrates. The relative contents of OA and MA were, respectively, 30:70 (w/w)
      and 77:23 (w/w). All concentrates also presented phenolic compounds at levels of
      g kg-1 and displayed slight antioxidant properties. CONCLUSION: Concentrates of
      TA, containing MA and OA, can be readily obtained from a byproduct generated by
      filtration of crude olive pomace oils. Concentrates isolated from oils obtained
      by centrifugation were rich in MA, whereas those from oils extracted with hexane
      were rich in OA. The concentrates showed slight antioxidant properties that can
      be mainly attributed to the presence of phenolic compounds and not to TA. (c)
      2018 Society of Chemical Industry.

PMID- 29574747
TI  - Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability:
      A study of 33 French cases.
AB  - Wiedemann-Steiner syndrome (WSS) is a rare syndromic condition in which
      intellectual disability (ID) is associated with hypertrichosis cubiti, short
      stature, and characteristic facies. Following the identification of the causative
      gene (KMT2A) in 2012, only 31 cases of WSS have been described precisely in the
      literature. We report on 33 French individuals with a KMT2A mutation confirmed by
      targeted gene sequencing, high-throughput sequencing or exome sequencing.
      Patients' molecular and clinical features were recorded and compared with the
      literature data. On the molecular level, we found 29 novel mutations. We observed
      autosomal dominant transmission of WSS in 3 families and mosaicism in one family.
      Clinically, we observed a broad phenotypic spectrum with regard to ID (mild to
      severe), the facies (typical or not of WSS) and associated malformations (bone,
      cerebral, renal, cardiac and ophthalmological anomalies). Hypertrichosis cubiti
      that was supposed to be pathognomonic in the literature was found only in 61% of
      our cases. This is the largest series of WSS cases yet described to date. A
      majority of patients exhibited suggestive features, but others were less
      characteristic, only identified by molecular diagnosis. The prevalence of WSS was
      higher than expected in patients with ID, suggesting than KMT2A is a major gene
      in ID.

PMID- 29574748
TI  - SIRT1 regulates nuclear number and domain size in skeletal muscle fibers.
AB  - Skeletal muscle fibers are giant multinucleated cells wherein individual nuclei
      govern the protein synthesis in a finite volume of cytoplasm; this is termed the
      myonuclear domain (MND). The factors that control MND size remain to be defined.
      In the present study, we studied the contribution of the NAD+ -dependent
      deacetylase, sirtuin 1 (SIRT1), to the regulation of nuclear number and MND size.
      For this, we isolated myofibers from mice with tissue-specific inactivation (mKO)
      or inducible overexpression (imOX) of SIRT1 and analyzed the 3D organisation of
      myonuclei. In imOX mice, the number of nuclei was increased whilst the average
      MND size was decreased as compared to littermate controls. Our findings were the
      opposite in mKO mice. Muscle stem cell (satellite cell) numbers were reduced in
      mKO muscles, a possible explanation for the lower density of myonuclei in these
      mice; however, no change was observed in imOX mice, suggesting that other factors
      might also be involved, such as the functional regulation of stem cells/muscle
      precursors. Interestingly, however, the changes in the MND volume did not impact
      the force-generating capacity of muscle fibers. Taken together, our results
      demonstrate that SIRT1 is a key regulator of MND sizes, although the underlying
      molecular mechanisms and the cause-effect relationship between MND and muscle
      function remain to be fully defined.

PMID- 29574749
TI  - Targeting EGFR-mediated autophagy as a potential strategy for cancer therapy.
AB  - Autophagy is a naturally occurring programed cellular catabolic process
      stimulated by cellular stress for energy homeostasis maintenance and elimination
      of harmful substances. It mostly works as pro-survival mechanism but on the other
      hand deregulation of autophagy has been linked to non-apoptotic cell death known
      as "type II programed cell death." Emerging evidences indicate that EGFR
      (epidermal growth factor receptor)-mediated RAS/RAF/MEK/ERK signaling pathway
      plays a critical role in the induction of autophagy in various tumors. It has
      further been established that this signaling pathway is also involved in several
      other anti-proliferative events such as apoptosis and senescence. However, the
      signaling pathway activity and effects are highly dependent on the cell type and
      the stimulus. It is currently being evident that autophagy induction by
      RAS/RAF/MEK/ERK pathway through small molecules may be a potential therapeutic
      strategy for cancer. However, to our best knowledge, the role of EGFR-mediated
      RAS/RAF/MEK/ERK signaling pathway in autophagy-mediated cell death and survival
      have not previously been reviewed. In this review, we discuss the current state
      of knowledge on how RAS/RAF/MEK/ERK signaling pathway regulates autophagy and the
      role of this EGFR-mediated autophagy in diseases. We further examine the cross
      talk between this EGFR-mediated autophagy and apoptosis as well as how this
      process is currently being utilized for cancer treatment and suggest promoting
      autophagy-related cell death by small molecules may be exploited to design better
      therapeutic strategies for early stage and locally advanced tumors.

PMID- 29574750
TI  - Impact of delayed umbilical cord clamping on public cord blood donations: can we
      help future patients and benefit infant donors?
AB  - BACKGROUND: Cord blood (CB) is a widely accepted stem cell source and its
      clinical utilization depends, to a great extent, on its cell content. Birth-to
      clamping (BTC) time of umbilical cord determines placental transfusion to the
      newborn, and the remaining blood that can be collected and banked. The 2017
      Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG)
      recommends a delay of "at least 30-60 seconds" before clamping the cord for all
      newborns to ensure adequate iron stores. The impact of delayed cord clamping
      (DCC) on public CB banking can be substantial. STUDY DESIGN AND METHODS: Cord
      blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for
      total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank
      staff recorded BTC time in seconds as reported by obstetricians; collections were
      performed ex utero. Immediate clamping was defined as BTC of less than 30
      seconds, whereas DCC was defined as BTC of 30 seconds or more. RESULTS: Cord
      clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries.
      Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60
      seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60
      seconds had significantly lower TNC counts than those after DCC of less than 60
      seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60
      seconds had volume of less than 40 mL. CONCLUSION: Our study indicates that DCC
      of 30 to 60 seconds has a small negative impact on collection of high-TNC-count
      CBUs. However, increasing BTC to more than 60 seconds decreases significantly
      both TNC content and volume, reducing drastically the chances of obtaining
      clinically useful CBUs.

PMID- 29574751
TI  - Surgical site infection in immediate breast reconstruction: Does chemotherapy
      timing make a difference?
AB  - BACKGROUND AND OBJECTIVES: We aim to analyze the impact of chemotherapy timing on
      surgical site infections (SSI) after immediate breast reconstruction (IBR).
      METHODS: A retrospective review of patients undergoing IBR between 2010 and 2015
      was performed. Patients were divided into four groups: those with neoadjuvant
      chemotherapy only, adjuvant chemotherapy only, both adjuvant and neoadjuvant, and
      those with no chemotherapy. Outcomes of interest included SSI and timing of post
      operative SSI. RESULTS: A total of 949 reconstructions were performed over the
      study period. Subgroup breakdown was as follows: A total of 56 (5.9%) neoadjuvant
      only, 173 (18.2%) adjuvant only, 18 (1.9%) both, and 702 (74.0%) none. Overall
      infection rates were 10.7%, 10.4%, 22.2%, and 6.1% in the four groups,
      respectively (P = 0.015). On multivariate analysis, no significant differences
      were observed when comparing presence or absence of chemotherapy in the overall
      reconstruction cohort or when subgrouped by reconstruction modality-autologous or
      alloplastic. There were no significant differences in time from neoadjuvant
      chemotherapy to surgery date noted between patients who developed a post
      operative SSI and those who did not (4.40 +/- 1.58 vs 4.72 +/- 1.39 weeks; P =
      0.517). CONCLUSION: Chemotherapy timing did not increase the odds of surgical
      site infections in patients undergoing immediate breast reconstruction.

PMID- 29574752
TI  - Whole body ARHGAP21 reduction improves glucose homeostasis in high-fat diet obese
      mice.
AB  - GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in
      cellular adhesion and membrane traffic processes have been well described.
      TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle
      cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4
      translocation, and consequently glucose uptake in adipocytes. Here, we assessed
      the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis.
      For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene
      deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21)
      were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD). Het
      HFD mice showed a reduction in white fat storage, reflected in a lower body
      weight gain. These mice also displayed an improvement in insulin sensitivity and
      glucose tolerance, which likely contributed to reduced insulin secretion and
      pancreatic beta cell area. The reduction of body weight was also observed in Het
      mice and this phenomenon was associated with an increase in brown adipose tissue
      and reduced muscle weight, without alteration in glucose-insulin homeostasis. In
      conclusion, the whole body ARHGAP21 reduction improved glucose homeostasis and
      protected against diet-induced obesity specifically in Het-HFD mice. However, the
      mechanism by which ARHGAP21 leads to these outcomes requires further
      investigation.

PMID- 29574753
TI  - Peeking at a plant through the holes in the wall - exploring the roles of
      plasmodesmata.
AB  - Plasmodesmata (PD) are membrane-lined pores that connect neighbouring plant cells
      and allow molecular exchange via the symplast. Past studies have revealed the
      basic structure of PD, some of the transport mechanisms for molecules through PD,
      and a variety of physiological processes in which they function. Recently, with
      the help of newly developed technologies, several exciting new features of PD
      have been revealed. New PD structures were observed during early formation of PD
      and between phloem sieve elements and phloem pole pericycle cells in roots. Both
      observations challenge our current understanding of PD structure and function.
      Research into novel physiological responses, which are regulated by PD, indicates
      that we have not yet fully explored the potential contribution of PD to overall
      plant function. In this Viewpoint article, we summarize some of the recent
      advances in understanding the structure and function of PD and propose the
      challenges ahead for the community.

PMID- 29574754
TI  - MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle.
AB  - Diabetes is a major risk factor for cardiovascular disease and this is in part
      due to the effects of hyperglycemia on vascular smooth muscle cells. Small non
      coding microRNAs are known to control smooth muscle phenotype and arterial
      contractility and are dysregulated in diabetes. The effect of microRNAs on smooth
      muscle differentiation is in part mediated by the transcription factor KLF4 but
      the role of this mechanism in diabetic vascular disease is not fully understood.
      Herein, we have investigated the importance of hyperglycemia and diabetes for the
      expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in
      this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle
      cells and similar results were found in arteries of diabetic mice and patients.
      This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted
      KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation
      of KLF4, the induction of smooth muscle contractile protein markers by glucose
      was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic
      conditions contributes to increased expression of contractile markers in vascular
      smooth muscle cells. Further studies are warranted to determine the therapeutic
      implications of miR-29 inhibition in diabetic vascular disease.

PMID- 29574755
TI  - Community health needs assessment: a nurses' global health project in Vietnam.
AB  - BACKGROUND: Global health has been directed to providing solutions to various
      health issues cross-nations, and nurses have received wide recognition as a key
      health workforce to reduce health disparities globally. Nurses involved in global
      health research are required to implement evidence-based global nursing practices
      based on the assessments of local health needs. AIM: To assess health needs and
      to suggest future interventions in rural communities of Vietnam. METHODS: A
      multifaceted rapid participatory appraisal with information pyramid was used
      applying mixed methods from six sources: existing record review, surveys of
      community residents, surveys of healthcare providers, focus group discussions
      with community leaders, informal discussions with governmental health
      administrators and observations of community health station (CHS) facilities.
      RESULTS: The majority used the CHSs as primary health facilities with high
      satisfaction for services currently provided. However, there were needs for the
      stations to provide more comprehensive services including chronic diseases, and
      for healthcare providers to improve their competences. Community leaders showed
      high interest in health information for chronic diseases and strong commitment to
      involvement in the activities for health of their communities. The findings
      suggest future interventions in the areas of the enhancement of CHS' functions,
      human resources and the self-care capacity of community residents. CONCLUSION AND
      POLICY IMPLICATIONS: The rapid participatory appraisal approach emphasizing
      community participation and partnership was a useful tool to compile accurate
      information about the current needs of the community on health, the preparedness
      of healthcare services to meet community's demands and about community capacity.
      This process is fundamental to nurses, who initiate global health projects in
      resource-limited international countries, to generate evidences regarding
      practice, research and policy for taking responsibilities in promoting the
      sustainable development goals.

PMID- 29574756
TI  - Oxycodone-induced tolerance to respiratory depression: reversal by ethanol,
      pregabalin and protein kinase C inhibition.
AB  - BACKGROUND AND PURPOSE: Oxycodone, a prescription opioid, is a major drug of
      abuse, especially in the USA, and contributes significantly to opioid overdose
      deaths each year. Overdose deaths result primarily from respiratory depression.
      We have studied respiratory depression by oxycodone and have characterized how
      tolerance develops on prolonged exposure to the drug. We have investigated the
      role of PKC in maintaining tolerance and have examined whether ethanol or
      pregabalin reverses oxycodone-induced tolerance. EXPERIMENTAL APPROACH:
      Respiration was measured in male CD-1 mice by whole-body plethysmography. Mice
      were preinjected with oxycodone then implanted with mini-pumps (s.c.) delivering
      20, 45 or 120 mg.kg-1 .day-1 oxycodone for 6 days and subsequently challenged
      with oxycodone (3 mg.kg-1 , i.p.) or morphine (10 mg.kg-1 , i.p.) to assess the
      level of tolerance. KEY RESULTS: Oxycodone-treated mice developed tolerance to
      oxycodone and cross tolerance to morphine-induced respiratory depression.
      Tolerance was less with 20 mg.kg-1 .day-1 than with 45 or 120 mg.kg-1 .day-1
      oxycodone treatment. At doses that do not depress respiration, ethanol (0.3 g.kg
      1 ), pregabalin (20 mg.kg-1 ) and calphostin C (45 MUg.kg-1 ) all reversed
      oxycodone-induced tolerance resulting in significant respiratory depression.
      Reversal of tolerance was less in mice treated with oxycodone (120 mg.kg-1 .day-1
      ). In mice receiving ethanol and calphostin C or ethanol and pregabalin, there
      was no greater reversal of tolerance than seen with either drug alone. CONCLUSION
      AND IMPLICATIONS: These data suggest that oxycodone-induced tolerance is mediated
      by PKC and that reversal of tolerance by ethanol or pregabalin may be a
      contributory factor in oxycodone overdose deaths.

PMID- 29574757
TI  - Residue investigation of some phenylureas and tebuthiuron herbicides in
      vegetables by ultra-performance liquid chromatography coupled with integrated
      selective accelerated solvent extraction-clean up in situ.
AB  - BACKGROUND: Some trace amounts of urea herbicide residues can be transferred to
      humans via the food chain, thereby being potentially harmful to human health. The
      development of a robust analytical methodology for effective sample preparation
      and simultaneous determination of herbicide residues in vegetable samples is
      required for achieving food safety. RESULTS: The diuron-molecularly imprinted
      polymers (MIPs) synthesized have excellent affinity and high selectivity to
      phenylureas (monolinuron, isoproturon, diuron and linuron) and tebuthiuron. A
      novel automated procedure with better selectivity for vegetable sample treatment
      was developed by integrated matrix solid-phase dispersion-accelerated solvent
      extraction clean-up in situ. Five herbicides can be baseline separated with
      runtime down to 5 min by ultra-performance liquid chromatography, and good
      linearity was obtained with a correlation coefficient (r) of 0.9999. The limit of
      quantification of the method was in the range of 0.8-2.3 ug kg-1 . Diuron residue
      in cherry tomato sample was found to be 40 ug kg-1 . CONCLUSION: The developed
      method has satisfactory selectivity, good linearity, high sensitivity and
      accuracy as well as speediness, and can ensure rapid selective extraction and
      sensitive multi-residue analysis at low microgram per kilogram levels of the
      herbicides in vegetable food. (c) 2018 Society of Chemical Industry.

PMID- 29574758
TI  - Childhood asthma clusters reveal neutrophil-predominant phenotype with distinct
      gene expression.
AB  - BACKGROUND: Childhood asthma comprises different phenotypes with complex
      pathophysiology. Different asthma phenotypes evoke various clinical symptoms and
      vary in their responses to treatments. METHODS: We applied k-means clustering
      algorithm of twelve objective laboratory tests among 351 asthmatic children
      enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We
      constructed gene expression profiles of peripheral blood mononuclear cells (PBMC)
      from children with different asthma phenotypes. RESULTS: Five distinct phenotypes
      of childhood asthma were identified and can be characterized by either eosinophil
      predominant or neutrophil-predominant inflammatory characteristics. In the gene
      expression profile analysis, significant differences were noted for neutrophil
      predominant asthma, compared with samples from all the other asthma phenotypes.
      The vast majority of the differentially expressed genes in neutrophil-predominant
      asthma was associated with corticosteroid response. From an independent inhaled
      corticosteroid (ICS) response cohort, we also found neutrophils could be
      activated in this severe asthma phenotype and neutrophil-predominant asthma may
      be associated with corticosteroid nonresponsiveness. CONCLUSION: Phenotype
      clustering of childhood asthma can be helpful to identify clinically relevant
      patients and reveal different inflammatory characteristics in asthmatic children.
      Neutrophil-predominant asthma is the most severe asthma phenotype with poor
      corticosteroid response. Gene expression profile of different asthma phenotypes
      not only improve our knowledge of childhood asthma, but also can guide asthma
      precision medicine.

PMID- 29574759
TI  - Humanizing the mouse immune system to study splanchnic organ inflammation.
AB  - It is well known that alterations in splanchnic organ perfusion and/or immune
      regulation may produce inflammatory tissue injury similar to that observed in
      several human disorders such as ischaemia and reperfusion injury, food allergies,
      diabetes, inflammatory bowel disease and graft-versus-host disease. Mouse models
      have been tremendously important in defining the roles of the circulation,
      leukocyte trafficking, inflammatory mediator generation, immune regulation and
      the intestinal microbiota in the pathogenesis of acute and chronic inflammation.
      However, few of the promising interventions or therapeutics reported in mouse
      models of inflammatory diseases have been translated to clinically effective
      treatments in patients. There is growing concern that because of the significant
      differences that exist between the murine and human immune systems, mouse models
      may not adequately recapitulate the immuno-pathogenesis of inflammatory diseases.
      This inconvenient reality has prompted a number of investigators to undertake a
      series of studies to humanize the murine immune system via adoptive transfer of
      human lymphoid or progenitor cells into a new generation of immuno-deficient
      recipients. In this review, we summarize the recent advances that have been made
      in the development of humanized mice and describe how these mouse models are
      being used to study the pathophysiology of splanchnic organ inflammation. In
      addition, we discuss the limitations of the different approaches and present
      potential solutions for the continued improvement of these important animal
      models.

PMID- 29574761
TI  - Effectiveness of calcium and vitamin D supplementation in osteoporosis.

PMID- 29574760
TI  - Dynamic probability of reinforcement for cooperation: Random game termination in
      the centipede game.
AB  - Experimental games have previously been used to study principles of human
      interaction. Many such games are characterized by iterated or repeated designs
      that model dynamic relationships, including reciprocal cooperation. To enable the
      study of infinite game repetitions and to avoid endgame effects of lower
      cooperation toward the final game round, investigators have introduced random
      termination rules. This study extends previous research that has focused narrowly
      on repeated Prisoner's Dilemma games by conducting a controlled experiment of two
      player, random termination Centipede games involving probabilistic reinforcement
      and characterized by the longest decision sequences reported in the empirical
      literature to date (24 decision nodes). Specifically, we assessed mean exit
      points and cooperation rates, and compared the effects of four different
      termination rules: no random game termination, random game termination with
      constant termination probability, random game termination with increasing
      termination probability, and random game termination with decreasing termination
      probability. We found that although mean exit points were lower for games with
      shorter expected game lengths, the subjects' cooperativeness was significantly
      reduced only in the most extreme condition with decreasing computer termination
      probability and an expected game length of two decision nodes.

PMID- 29574763
TI  - Subgingival glycine powder air-polishing as an additional approach to nonsurgical
      periodontal therapy in subjects with untreated chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Glycine powder air-polishing (GPAP) is an alternative
      approach to removing subgingival plaque biofilms for effective periodontal
      therapy. This study aimed to investigate the effect of subgingival GPAP as an
      additional approach to nonsurgical periodontal treatment in subjects with chronic
      periodontitis. MATERIAL AND METHODS: Twenty-seven nonsmoking subjects were
      recruited. Two quadrants in each subject were randomly assigned, according to a
      split-mouth design, to receive scaling and root planing (SRP) and GPAP (Test
      group) or SRP and air flushing with water (Control group) at sites with probing
      depth >=5 mm. Clinical parameters, gingival crevicular fluid volumes and the
      concentrations of interleukin-1beta and interleukin-1ra in gingival crevicular
      fluid were measured at baseline and 1, 3 and 6 months after the treatments.
      RESULTS: At baseline, no statistically significant difference in periodontal and
      gingival crevicular fluid parameters was found between the Test and Control
      groups. Overall, the periodontal conditions of all subjects showed significant
      improvement after the treatments. Notably, the Test group showed greater
      reduction in gingival crevicular fluid volume (0.37 +/- 0.26 MUL) than the
      Control group (0.23 +/- 0.30 MUL) at 3 months (P < .05). The gingival crevicular
      fluid levels of interleukin-1beta and interleukin-1ra showed a significant
      decrease in both groups at 6 months, and no significant difference was found
      between the groups. CONCLUSION: These preliminary results suggest that GPAP, as
      an additional approach to nonsurgical periodontal treatment, may be beneficial
      for the short-term improvement of subclinical inflammation when measured by
      gingival crevicular fluid volume. Further longitudinal studies with larger sample
      sizes are required to clarify the exact benefits of GPAP treatment for
      controlling inflammation and maintaining long-term periodontal health.

PMID- 29574762
TI  - Deficient arginase II expression without alteration in arginase I expression
      attenuated experimental autoimmune encephalomyelitis in mice.
AB  - In the past there have been a multitude of studies that ardently support the role
      of arginase II (Arg II) in vascular and endothelial disorders; however, the
      regulation and function of Arg II in autoimmune diseases has thus far remained
      unclear. Here we report that a global Arg II null mutation in mice suppressed
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis. During EAE, both Arg I and Arg II were induced in spinal cords, but
      only Arg II was induced in spleens and splenic dendritic cells (DCs). DC
      activation by lipopolysaccharide (LPS), CD40L or TLR8 agonist significantly
      enhanced Arg II expression without affecting Arg I expression. Conversely, DC
      differentiating cytokines [IL-4 and granulocyte macrophage-colony-stimulating
      factor (GM-CSF)] yielded opposite effects. In addition, Arg I and Arg II were
      regulated differentially during Th1 and Th17 cell polarization. Arg II deficiency
      in mice delayed EAE onset, ameliorated clinical symptoms and reduced myelin loss,
      accompanied by a remarkable reduction in the EAE-induced spinal cord expression
      of Th17 cell markers (IL-17 and RORgammat). The abundance of Th17 cells and IL
      23+ cells in relevant draining lymph nodes was significantly reduced in Arg II
      knockout mice. In activated DCs, Arg II deficiency significantly suppressed the
      expression of Th17-differentiating cytokines IL-23 and IL-6. Interestingly, Arg
      II deficiency did not lead to any compensatory increase in Arg I expression in
      vivo and in vitro. In conclusion, Arg II was identified as a factor promoting EAE
      likely via an Arg I-independent mechanism. Arg II may promote EAE by enhancing DC
      production of Th17-differentiating cytokines. Specific inhibition of Arg II could
      be a potential therapy for multiple sclerosis.

PMID- 29574764
TI  - Comparison of tear proteome in allergic rhinoconjunctivitis patients and controls
      with respect to pollen season.

PMID- 29574766
TI  - In vitro evaluation of di(2-ethylhexyl)terephthalate-plasticized polyvinyl
      chloride blood bags for red blood cell storage in AS-1 and PAGGSM additive
      solutions.
AB  - BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) makes polyvinyl chloride flexible
      for use in blood bags and stabilizes the red blood cell (RBC) membrane preventing
      excessive hemolysis. DEHP migrates into the blood product and rodent studies have
      suggested that DEHP exposure may be associated with adverse health effects albeit
      at high dosages. Although structurally and functionally similar to DEHP, di(2
      ethylhexyl)terephthalate (DEHT; or Eastman 168 SG [Eastman Chemical Company]) is
      metabolically distinct with a comprehensive and benign toxicology profile. This
      study evaluated RBC stability in DEHT-plasticized bags with AS-1 and PAGGSM
      compared to conventional DEHP-plasticized bags with AS-1. STUDY DESIGN AND
      METHODS: Thirty-six whole blood units were collected into CPD solution,
      leukoreduced, centrifuged, and divided into RBCs and plasma. To limit donor
      related variability, three ABO-identical RBCs were mixed together and then
      divided equally and stored among the three different plasticizer and additive
      solution combinations. RBCs from 12 trios were analyzed for a standard panel of
      in vitro variables on Day 0 and after storage. RESULTS: No individual bag on Day
      42 exceeded the US 1.0% hemolysis criteria. While hemolysis during storage was
      higher in the DEHT bags, the PAGGSM RBCs were close to the control RBCs (0.38%
      vs. 0.32%, respectively). ATP retention was higher than 70% and potassium levels
      were similar regardless of plasticizer. Additional RBC variables exhibited some
      significant differences but were not viewed as clinically important. CONCLUSION:
      DEHT/PAGGSM provides similar hemolysis protection to that of DEHP/AS-1. Although
      hemolysis values with DEHT and AS-1 are higher than that of DEHP, DEHT is a
      potential DEHP alternative.

PMID- 29574765
TI  - Direct solid-state evidence of H2 -induced partial U(VI) reduction concomitant
      with adsorption by extracellular polymeric substances (EPS).
AB  - Adsorption of hexavalent uranium (U(VI)) by extracellular polymeric substances
      (EPS) has been studied, but the possibility of simultaneous U(VI) reduction
      mediated by EPS has not had experimental confirmation, as the reduction products
      have not yet been directly proven. Here, we reported the first direct evidence of
      lower-valent products of U(VI) immobilization by loosely associated EPS (laEPS)
      isolated from a fermenter strain of Klebsiella sp. J1 when the laEPS was exposed
      to H2 . During the 120-min tests for similarly 86% adsorption under O2 , N2 , and
      H2 , 8% more U was immobilized through a non-adsorptive pathway by the EPS for H2
      than for N2 and O2 . A set of solid-state characterization tools (FT-IR, XPS,
      EELS, and TEM-EDX) confirmed partial reduction of U(VI) to lower-valence U, with
      the main reduced form being uraninite (UIV O2 ) nanoparticles, and the results
      reinforced the role of the reduction in accelerating U immobilization and shaping
      the characteristics of immobilized U in terms of valency, size, and
      crystallization. The laEPS, mostly comprised of carbohydrate and protein,
      contained non-cytochrome enzymes and electron carriers that could be responsible
      for electron transfer to U(VI). Taken together, our results directly confirm that
      EPS was able to mediate partial U(VI) reduction in the presence of H2 through non
      cytochrome catalysis and that reduction enhanced overall U immobilization. Our
      study fills in some gaps of the microbe-mediated U cycle and will be useful to
      understand and control U removal in engineered reactors and in-situ
      bioremediation.

PMID- 29574767
TI  - Patient-specific estimation of spatially variant image noise for a pinhole
      cardiac SPECT camera.
AB  - PURPOSE: New single photon emission computed tomography (SPECT) cameras using
      fixed pinhole collimation are increasingly popular. Pinhole collimators are known
      to have variable sensitivity with distance and angle from the pinhole aperture.
      It follows that pinhole SPECT systems will also have spatially variant
      sensitivity and hence spatially variant image noise. The objective of this study
      was to develop and validate a rapid method for analytically estimating a map of
      the noise magnitude in a reconstructed image using data from a single clinical
      acquisition. METHODS: The projected voxel (PV) noise estimation method uses a
      modified forward projector with attenuation effects to estimate the number of
      photons detected from each voxel in the field-of-view. We approximate the noise
      for each voxel as the standard deviation of a Poisson distribution with a mean
      equal to the number of detected photons. An empirical formula is used to address
      scaling discrepancies caused by image reconstruction. Calibration coefficients
      are determined for the PV method by comparing it with noise measured from a
      nonparametrically bootstrapped set of images of a spherical uniformly filled Tc
      99m water phantom. Validation studies compare PV noise estimates with
      bootstrapped measured noise for 31 patient images (5 min, 340 MBq, 99m Tc
      tetrofosmin rest study). RESULTS: Bland-Altman analysis shows R2 correlations
      >=70% between the PV-estimated and -measured image noise. For the 31 patient
      cardiac images, the PV noise estimate has an average bias of 0.1% compared to
      bootstrapped noise and have a coefficient of variation (CV) <= 17%. The bootstrap
      approach to noise measurement requires 5 h of computation for each image, whereas
      the PV noise estimate requires only 64 s. In cardiac images, image noise due to
      attenuation and camera sensitivity varies on average from 4% at the apex to 9% in
      the basal posterior region of the heart. The standard deviation between 15
      healthy patient study images (including physiological variability in the
      population) ranges from 6% to 16.5% over the length of the heart. CONCLUSIONS:
      The PV method provides a rapid estimate for spatially variant patient-specific
      image noise magnitude in a pinhole-collimated dedicated cardiac SPECT camera with
      a bias of -0.3% and better than 83% precision.

PMID- 29574768
TI  - Histone methylation and acetylation in macrophages as a mechanism for regulation
      of inflammatory responses.
AB  - Macrophages respond to noxious stimuli and contribute to inflammatory responses
      by eliminating pathogens or damaged tissue and maintaining homeostasis. Response
      to activation signals and maintenance of homeostasis require tight regulation of
      genes involved in macrophage activation and inactivation processes, as well as
      genes involved in determining their polarization state. Recent evidence has
      revealed that such regulation occurs through histone modifications that render
      inflammatory or polarizing gene promoters accessible to transcriptional
      complexes. Thus, inflammatory and anti-inflammatory genes are regulated by
      histone acetylation and methylation, determining their activation state. Herein,
      we review the current knowledge on the role of histone modifying enzymes
      (acetyltransferases, deacetylases, methyltransferases, and demethylases) in
      determining the responsiveness and M1 or M2 polarization of macrophages. The
      contribution of these enzymes in the development of inflammatory diseases is also
      presented.

PMID- 29574769
TI  - Crystal structure of exo-rhamnogalacturonan lyase from Penicillium chrysogenum as
      a member of polysaccharide lyase family 26.
AB  - Exo-rhamnogalacturonan lyase from Penicillium chrysogenum 31B (PcRGLX) was
      recently classified as a member of polysaccharide lyase (PL) family 26 along with
      hypothetical proteins derived from various organisms. In this study, we
      determined the crystal structure of PcRGLX as the first structure of a member of
      this family. Based on the substrate-binding orientation and substrate
      specificity, PcRGLX is an exo-type PL that cleaves rhamnogalacturonan from the
      reducing end. Analysis of PcRGLX-complex structures with reaction products
      indicate that the active site possesses an L-shaped cleft that can accommodate
      galactosyl side chains, suggesting side-chain-bypassing activity in PcRGLX.
      Furthermore, we determined the residues critical for catalysis by analyzing the
      enzyme activities of inactive variants.

PMID- 29574770
TI  - The origin of aliphatic hydrocarbons in olive oil.

PMID- 29574771
TI  - Monoclonal antibody-based therapeutics, targeting the epidermal growth factor
      receptor family: from herceptin to Pan HER.
AB  - OBJECTIVES: Monoclonal antibody-based of cancer therapy has been considered as
      one of the most successful therapeutic strategies for both haematologic
      malignancies and solid tumours in the last two decades. Epidermal growth factor
      receptor (EGFR) family signalling pathways play a key role in the regulation of
      cell proliferation, survival and differentiation. Hence, anti-EGFR family mAbs is
      one of the most promising approaches in cancer therapy. KEY FINDINGS: Here,
      recent advances in anti-EGFR mAb including approved or successfully tested in
      preclinical and clinical studies have been reviewed. Although we focus on
      monoclonal antibodies against the EGF receptor, but the mechanisms underlying the
      effects of EGFR-specific mAb in cancer therapy, to some extend the resistance to
      existing anti-EGFR therapies and some therapeutic strategies to overcome
      resistance such as combination of mAbs on different pathways are briefly
      discussed as well. SUMMARY: The EGFR family receptors, is considered as an
      attractive target for mAb development to inhibit their consecutive activities in
      tumour growth and resistance. However, due to resistance mechanisms, the
      combination therapies may become a good candidate for targeting EGFR family
      receptors.

PMID- 29574772
TI  - Omental calcification, necrotizing enterocolitis, and undescended testes after
      fetal abdomino-amniotic shunting performed for the management of meconium
      peritonitis: A case report.
AB  - Prenatal ultrasonography (US) in a 39 year-old woman revealed massive fetal
      ascites. A fetal abdomino-amniotic shunting procedure was performed.
      Subsequently, plain radiographs demonstrated diffuse gaseous distention of the
      bowel and multiple punctate calcifications in the left upper abdomen. Postnatal
      US examination showed multiple echogenic foci in the liver and the left upper
      abdomen, bowel wall thickening in the right-sided abdomen, and undescended
      testes. There was no intra-abdominal free air or loculated fluid collections.
      Medical management was instituted secondary to the clinical suspicion of omental
      calcification, necrotizing enterocolitis, and undescended testes. Follow-up US
      examination showed resolution of portal vein gas and bowel wall thickening. The
      neonate recovered fully.

PMID- 29574773
TI  - Omega-3 fatty acids modulate the lipid profile, membrane architecture, and gene
      expression of leiomyoma cells.
AB  - Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of
      premenopausal women and new medical treatments are needed. This study aimed to
      determine the effects of omega-3 fatty acids on the lipid profile, membrane
      architecture and gene expression patterns of extracellular matrix components
      (collagen1A1, fibronectin, versican, or activin A), mechanical signaling
      (integrin beta1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1,
      CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma
      cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma
      tissues while leiomyoma tissues had a higher level of linoleic acid than
      myometrial tissues. Treatment of primary myometrial and leiomyoma cells with
      eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the
      monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty
      acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes
      were in the liquid-crystalline phase, but EPA- and DHA-treated cells had
      decreased membrane fluidity. While we found no changes in the mRNA expression of
      ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13
      in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in
      myometrial cells. The ability of omega-3 fatty acids to remodel membrane
      architecture and downregulate the expression of genes involved in mechanical
      signaling and lipid accumulation in leiomyoma cells offers to further investigate
      this compound as preventive and/or therapeutic option.

PMID- 29574774
TI  - Surging HIV-1 CRF07_BC epidemic among recently infected men who have sex with men
      in Fujian, China.
AB  - A rapidly increasing number of HIV-1 infections have been identified among men
      who have sex with men (MSM) in Fujian province of China since 2010. We aimed to
      investigate the causative factors underlying this surging epidemic. Using
      immunoassays for HIV-1 diagnosis and phylogenetic analysis for viral genotyping,
      we found that the number of MSM infections doubled from 171 in 2011 to 340 in
      2013 with a significantly increased prevalent rate from 4.1% to 5.2%. Majority of
      these increased infections took place in Fuzhou, Xiamen, and Quanzhou, three
      large cities in Fujian, mainly among youth, unemployed, business, and well
      educated MSMs. Phylogenetic analysis revealed three major HIV-1 genotypes
      including CRF01_AE, CRF07_BC, and B/B' yet the surging MSM infections were
      primarily associated with the rapid sexual spread of CRF07_BC in addition to
      CRF01_AE. In particular, there was a significant proportional expansion of
      CRF07_BC infections among recently infected MSMs from 19% in 2012 to 41.9% in
      2013. This increase was accompanied by emergence of complex patterns of viral
      recombination including multiple hybrid variants derived from CRF01_AE and
      CRF07_BC. Full-genome analysis indicated that CRF07_BC in Fujian was likely
      originated from similar strains previously found among IDUs in Yunnan province
      but with unique recombination break points. Our findings indicated that HIV-1
      CRF07_BC has adapted for rapid sexual transmission, resulting in the surging HIV
      1 epidemic and the emergence of new recombinant strains among MSMs in Fujian. Our
      findings have implications to vaccine and passive immunization trials in Fujian
      with emphasis on the induction of cross-subtype protective immunity.

PMID- 29574775
TI  - Internet interventions help patients newly diagnosed with cancer improve their
      quality of life.

PMID- 29574776
TI  - Brain Monitoring Devices in Neuroscience Clinical Research: The Potential of
      Remote Monitoring Using Sensors, Wearables, and Mobile Devices.
AB  - The increasing miniaturization and affordability of sensors and circuitry has led
      to the current level of innovation in the area of wearable and microsensor
      solutions for health monitoring. This facilitates the development of solutions
      that can be used to measure complex health outcomes in nonspecialist and remote
      settings. In this article, we review a number of innovations related to brain
      monitoring including portable and wearable solutions to directly measure brain
      electrical activity, and solutions measuring aspects related to brain function
      such as sleep patterns, gait, cognition, voice acoustics, and gaze analysis.
      Despite the need for more scientific validation work, we conclude that there is
      enough understanding of how to implement these approaches as exploratory tools
      that may provide additional valuable insights due to the rich and frequent data
      they produce, to justify their inclusion in clinical study protocols.

PMID- 29574777
TI  - Doppler Renal Resistance Index for the Prediction of Response to Passive Leg
      Raising Following Cardiac Surgery.
AB  - PURPOSE: Doppler-based renal resistance index (RI) can be measured at the bedside
      of critically ill patients. This study was designed to assess if the RI predicted
      an increase in cardiac output (CO) following passive leg-raising (PLR) in
      patients admitted to the intensive care unit after cardiac surgery. METHODS:
      During this single center prospective study, Doppler assessment of RI and
      measurements of CO using the thermodilution method were performed, after surgery,
      in the intensive care unit before and after PLR. A positive response to PLR was
      defined as a >=10% increase in CO. RESULTS: We included 30 patients. The mean RI
      was higher before (0.694 +/-0.069) than after PLR (0.679 +/- 0.069) (P = .02)
      with a median change of -0.012 (IQR: -0.042;0.000). Following PLR, 9 patients
      (30%) had a >10% increase in CO. In patients with a positive PLR response, the
      decrease in the RI during PLR was more pronounced than in patients who did not
      respond to PLR (PLR +/- 0.042 (IQR: -0.051; -0.040) vs PLR +/- -0.008 (IQR: 
      0.032; 0.015) (P = .004). There was a significant negative association between RI
      change in response to PLR and a 10% increase in CO following PLR (OR: 1.63
      (CI:1.07-2.47) (P = .02) per -0.01 change). CONCLUSION: An increase in CO
      following PLR was associated with a significant decrease in RI. Variations of RI
      in response to PLR should be further studied as a tool to predict fluid
      responsiveness. However, their clinical utility could be limited by the small
      magnitude of the variations.

PMID- 29574778
TI  - Arabidopsis DORN1 extracellular ATP receptor; activation of plasma membrane K+ 
      and Ca2+ -permeable conductances.

PMID- 29574779
TI  - A DEAD-box RNA helicase, RH8, is critical for regulation of ABA signalling and
      the drought stress response via inhibition of PP2CA activity.
AB  - Abscisic acid (ABA) is major plant hormone involved in regulating abiotic stress
      responses. Several studies have established that an ABA-signalling transduction
      pathway-from ABA perception to response-functions in plant cells. The group A
      PP2Cs constitute core components of ABA signalling, and they negatively regulate
      ABA signalling and stress responses. Recent studies have identified and
      functionally analysed regulators of PP2C activity; however, the precise
      regulatory mechanisms remain unclear. In the present study, we used a yeast 2
      hybrid (Y2H) screening analysis to identify the DEAD-box RNA helicase RH8, which
      interacted with PP2CA in the nucleus. rh8 knockout mutants exhibited ABA
      hyposensitivity and drought-susceptible phenotypes characterized by high levels
      of transpirational water loss via reduced stomatal closure and decreased leaf
      temperatures. However, rh8/pp2ca double mutants showed ABA hypersensitivity and
      drought-tolerant phenotypes, indicating that RH8 and PP2CA function in the same
      ABA-signalling pathway in the drought stress response; moreover, RH8 functions
      upstream of PP2CA. In vitro phosphatase and kinase assays revealed that RH8
      inhibits PP2CA phosphatase activity. Our data indicate that RH8 and its
      interacting partner PP2CA modulate the drought stress response via ABA-dependent
      signalling.

PMID- 29574780
TI  - Prevalence of depressive symptoms in older nursing home residents with intact
      cognitive function in Taiwan.
AB  - The investigators aimed to explore the prevalence of depressive symptoms and
      associated factors among older residents with intact cognitive function in
      nursing homes in Taiwan. A cross-sectional descriptive and correlational research
      design was used. A convenience sample of 178 older residents without cognitive
      impairment was recruited from 36 nursing homes in Southern Taiwan. The
      questionnaires included demographic data; the Barthel Index, which assesses the
      ability to perform activities of daily living; and the Geriatric Depression Scale
      Short Form. Among older residents in nursing homes with intact cognitive
      function, 39.3% had depressive symptoms. Age, religion, previous living status,
      previous working status, being totally dependent in physical function, and being
      severely dependent in physical function were significant predictors of depressive
      symptoms among cognitively intact older residents. The findings highlight the
      critical mental healthcare issues among older residents with intact cognitive
      function in nursing homes. Practical strategies for preventing the occurrence of
      depressive symptoms and caring for those who have depressive symptoms should be
      developed, especially for younger or dependent older residents or residents who
      have never been employed, have no religious beliefs, or have lived alone before
      they moved into an institution.

PMID- 29574782
TI  - Rab9-dependent autophagy is required for the IGF-IIR triggering mitophagy to
      eliminate damaged mitochondria.
AB  - Mitochondria dysfunction is the major characteristic of mitophagy, which is
      essential in mitochondrial quality control. However, excessive mitophagy
      contributes to cell death in a number of diseases, including ischemic stroke and
      hepatotoxicity. Insulin-like growth factor II (IGF-II) and its receptor (IGF-IIR)
      play vital roles in the development of heart failure during hypertension. We
      found that IGF-II triggers IGF-IIR receptor activation, causing mitochondria
      dysfunction, resulting in mitophagy, and cardiomyocyte cell death. These results
      indicated that IGF-IIR activation triggers mitochondria fragmentation, leading to
      autophagosome formation, and loss of mitochondria content. These results are
      associated with Parkin-dependent mitophagy. Additionally, autophagic proteins
      Atg5, and Atg7 deficiency did not suppress IGF-IIR-induced mitophagy. However,
      Rab9 knockdown reduced mitophagy and maintained mitochondrial function. These
      constitutive mitophagies through IGF-IIR activation trigger mitochondria loss and
      mitochondrial ROS accumulation for cardiomyocyte viability decrease. Together,
      our results indicate that IGF-IIR predominantly induces mitophagy through the
      Rab9-dependent alternative autophagy.

PMID- 29574781
TI  - Time course of cytochrome oxidase blob plasticity in the primary visual cortex of
      adult monkeys after retinal laser lesions.
AB  - We studied the time course of changes of cytochrome oxidase (CytOx) blob spatial
      density and blob cross-sectional area of deprived (D) and nondeprived (ND)
      portions of V1 in four capuchin monkeys after massive and restricted retinal
      laser lesions. Laser shots at the border of the optic disc produced massive
      retinal lesions, while low power laser shots in the retina produced restricted
      retinal lesions. These massive and restricted retinal lesions were intended to
      simulate glaucoma and diabetic retinopathy, respectively. We used a Neodymium-YAG
      dual frequency laser to make the lesions. We measured Layer III blobs in CytOx
      reacted tangential sections of flat-mounted preparations of V1. The plasticity of
      the blob system and that of the ocular dominance columns (ODC) varied with the
      degree of retinal lesions. We found that changes in the blob system were
      different from that of the ODC. Blob sizes changed drastically in the region
      corresponding to the retinal lesion. Blobs were larger and subjectively darker
      above and below the non deprived ODC than in the deprived columns. With
      restricted lesions, blobs corresponding to the ND columns had sizes similar to
      those from non-lesioned areas. In contrast, blobs corresponding to the deprived
      columns were smaller than those from nonlesioned areas. With massive lesions, ND
      blobs were larger than the deprived blobs. Plastic changes in blobs described
      here occur much earlier than previously described.

PMID- 29574783
TI  - Management of unrecognized bladder perforation following suburethral tape
      procedure.

PMID- 29574784
TI  - New thermomechanically treated NiTi alloys - a review.
AB  - In the past 10 years, several proprietary processing procedures for nickel
      titanium (NiTi) alloy were developed to improve the mechanical properties of NiTi
      endodontic instruments. Beside specific thermal and mechanical treatments,
      manufacturers introduced several machining procedures (e.g. twisting, electrical
      discharge machining), as well as techniques for final surface finishing. NiTi
      alloys used for endodontic instruments can be subdivided into instruments that
      mainly contain the austenite phase (austenitic: conventional NiTi, M-Wire, R
      Phase) and those mainly containing the martensite phase (martensitic: CM Wire,
      Gold and Blue heat-treated NiTi). Thermomechanically treated NiTi alloys have
      been reported to be more flexible with improved cyclic fatigue resistance and
      greater angle of deflection at failure when compared to conventional NiTi. These
      enhanced properties may be attributed to a modified phase composition containing
      varying amounts of R-phase and martensite. Endodontic instruments made of
      austenitic alloys possess superelastic properties because of stress-induced
      martensite transformation and consequently tend to spring-back to their original
      form after deformation. In contrast, the martensitic instruments can easily be
      deformed due to the reorientation of the martensite variants and show a shape
      memory effect when heated. The use of martensitic alloy results in more flexible
      instruments, with an increased cyclic fatigue resistance compared with austenitic
      alloy.

PMID- 29574785
TI  - Resident alveolar macrophages are master regulators of arrested alveolarization
      in experimental bronchopulmonary dysplasia.
AB  - Trophic functions for macrophages are emerging as key mediators of developmental
      processes, including bone, vessel, and mammary gland development. Yolk sac
      derived macrophages mature in the distal lung shortly after birth. Myeloid
      lineage macrophages are recruited to the lung and are activated under
      pathological conditions. These pathological conditions include bronchopulmonary
      dysplasia (BPD), a common complication of preterm birth characterized by stunted
      lung development, where the formation of alveoli is blocked. No study has
      addressed causal roles for immune cells in lung alveolarization. We employed
      antibody-based and transgenic death receptor-based depletion approaches to
      deplete or prevent lung recruitment of immune cell populations in a hyperoxia
      based mouse model of BPD. Neither neutrophils nor exudate macrophages (which
      might include lung interstitial macrophages) contributed to structural
      perturbations to the lung that were provoked by hyperoxia; however, cells of the
      Csf1r-expressing monocyte/macrophage lineage were implicated as causal mediators
      of stunted lung development. We propose that resident alveolar macrophages
      differentiate into a population of CD45+ CD11c+ SiglecF+ CD11b+ CD68+ MHCII+
      cells, which are activated by hyperoxia, and contribute to disturbances to the
      structural development of the immature lung. This is the first report that
      causally implicates immune cells in pathological disturbances to postnatal lung
      organogenesis. Copyright (c) 2018 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29574786
TI  - Immune checkpoint inhibitors are superior to docetaxel as second-line therapy for
      patients with non-small cell lung carcinoma.

PMID- 29574787
TI  - Multiple drug intolerance syndrome and multiple drug allergy syndrome:
      Epidemiology and associations with anxiety and depression.
AB  - BACKGROUND: The epidemiology of multiple drug intolerance syndrome (MDIS) and
      multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic
      health record (EHR) data to describe prevalences of MDIS and MDAS and to examine
      associations with anxiety and depression. METHODS: Patients with >=3 outpatient
      encounters at Partners HealthCare System from 2008 to 2015 were included.
      Patients with MDIS had intolerances to >=3 drug classes, and patients with MDAS
      had hypersensitivities to >=2 drug classes. Psychiatric conditions and
      comorbidities were defined from the EHR and used in multivariable logistic
      regression models to assess the relation between anxiety/depression and
      MDIS/MDAS. RESULTS: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%)
      had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65,
      1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR
      1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was
      associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no
      clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and
      anxiety (aOR 1.13 [0.92, 1.38]). CONCLUSION: While 6% of patients had MDIS, only
      1% had MDAS. MDIS was associated with both anxiety and depression; patients with
      both anxiety and depression had an almost twofold increased odds of MDIS. MDAS
      was associated with a 40% increased odds of depression, but there was no
      significant association with anxiety. Psychological assessments may be useful in
      the evaluation and treatment of patients with MDIS and MDAS; physiologic causes
      for MDAS warrant further investigation.

PMID- 29574789
TI  - American Society for Laser Medicine and Surgery Abstracts.

PMID- 29574788
TI  - Mechanisms underlying lesion development and lesion distribution in CNS
      autoimmunity.
AB  - It is widely accepted that development of autoimmunity in the central nervous
      system (CNS) is triggered by autoreactive T cells, that are activated in the
      periphery and gain the capacity to migrate through endothelial cells at the blood
      brain barrier (BBB) into the CNS. Upon local reactivation, an inflammatory
      cascade is initiated, that subsequently leads to a recruitment of additional
      immune cells ultimately causing demyelination and axonal damage. Even though the
      interaction of immune cells with the BBB has been in the focus of research for
      many years, the exact mechanisms of how immune cells enter and exit the CNS
      remains poorly understood. In this line, the factors deciding immune cell entry
      routes, lesion formation, cellular composition as well as distribution within the
      CNS have also not been elucidated. The following factors have been proposed to
      represent key determinants for lesion evaluation and distribution: (i) presence
      and density of (auto) antigens in the CNS, (ii) local immune milieu at sites of
      lesion development and resolution, (iii) trafficking routes and specific
      trafficking requirements, especially at the BBB and (iv) characteristics and
      phenotypes of CNS infiltrating cells and cell subsets (e.g. features of T helper
      subtypes or CD8 cells). The heterogeneity of lesion development within
      inflammatory demyelinating diseases remains poorly understood until today, but
      here especially orphan inflammatory CNS disorders such as neuromyelitis optica
      spectrum disorder (NMOSD), Rasmussen encephalitis or SUSAC syndrome might give
      important insights in critical determinants of lesion topography. Finally,
      investigating the interaction of T cells with the BBB using in vitro approaches
      or tracking of T cells in vivo in animals or even human patients, as well as the
      discovery of lymphatic vasculature in the CNS are teaching us new aspects during
      the development of CNS autoimmunity. In this review, we discuss recent findings
      which help to unravel mechanisms underlying lesion topography and might lead to
      new diagnostic or therapeutic approaches in neuroinflammatory disorders including
      multiple sclerosis (MS).

PMID- 29574790
TI  - The role of enhancer of zeste homolog 2: From viral epigenetics to the
      carcinogenesis of hepatocellular carcinoma.
AB  - Nowadays, epigenetics covers a crucial role in different fields of science. The
      enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb
      Repressive Complex 2 (PRC2), is a big proponent of how epigenetic changes can
      affect the initiation and progression of several diseases. Through its catalytic
      activity, responsible for the tri-methylation of lysine 27 of the histone H3
      (H3K27me3), EZH2 is a good target for both diagnosis and therapy of different
      pathologies. A large number of studies have demonstrated its crucial role in
      cancer initiation and progression. Nevertheless, only recently its function in
      virus diseases has been uncovered; therefore, EZH2 can be an important promoter
      of viral carcinogenesis. This review explores the role of EZH2 in viral
      epigenetics based on recent progress that demonstrated the role of this protein
      in virus environment. In particular, the review focuses on EZH2 behavior in
      Hepatitis B Virus, analyzing its role in the rise of Hepatocellular Carcinoma.

PMID- 29574791
TI  - Inhibition of human prostate smooth muscle contraction by the LIM kinase
      inhibitors, SR7826 and LIMKi3.
AB  - BACKGROUND AND PURPOSE: In men with benign prostatic hyperplasia, increased
      smooth muscle tone in the prostate may lead to bladder outlet obstruction and
      subsequent lower urinary tract symptoms. Consequently, medical treatment aims to
      inhibit prostate smooth muscle contraction. However, the efficacy of the
      treatment options available is limited, and improved understanding of mechanisms
      of prostate smooth muscle contraction and identification of new targets for
      medical intervention are mandatory. Several studies suggest that LIM kinases
      (LIMKs) promote smooth muscle contraction; however, this has not yet been
      examined. Here, we studied effects of the LIMK inhibitors on prostate smooth
      muscle contraction. EXPERIMENTAL APPROACH: Human prostate tissues were obtained
      from radical prostatectomy. Phosphorylation of cofilin, a LIMK substrate, was
      examined using a phospho-specific antibody. Smooth muscle contractions were
      studied in organ bath experiments. KEY RESULTS: Real-time PCR, Western blot and
      immunofluorescence suggested LIMKs are expressed in smooth muscle cells of
      prostate tissues. Two different LIMK inhibitors, SR7826 (1 MUM) and LIMKi3 (1
      MUM), inhibited contractions of prostate strips, which were induced by electrical
      field stimulation, alpha1 -adrenoceptor agonists phenylephrine and methoxamine
      and the TXA2 analogue, U46619. LIMK inhibition in prostate tissues and cultured
      stromal cells (WPMY-1) was confirmed by cofilin phosphorylation, which was
      reduced by SR7826 and LIMKi3. In WPMY-1 cells, SR7826 and LIMKi3 caused breakdown
      of actin filaments and reduced viability. CONCLUSIONS AND IMPLICATIONS: Smooth
      muscle tone in the hyperplastic human prostate may underlie the effects of LIMKs,
      which promote contraction. Contraction of prostate strips can be inhibited by
      small molecule LIMK inhibitors.

PMID- 29574792
TI  - Reduced Variability to Aspirin Antiplatelet Effect by the Coadministration of
      Statins in High-Risk Patients for Cardiovascular Disease.
AB  - We studied the influence of cardiovascular (CV) risk factors, previous CV events,
      and cotreatments with preventive medicines, on residual platelet thromboxane
      (TX)B2 production in 182 patients chronically treated with enteric coated (EC)
      aspirin (100 mg/day). The response to aspirin was also verified by assessing
      arachidonic acid-induced platelet aggregation and urinary 11-dehydro-TXB2 levels.
      Residual serum TXB2 levels exceeded the upper limit value for an adequate aspirin
      response in 14% of individuals. This phenomenon was detected at 12 hours after
      dosing with aspirin. The coadministration of statins (mostly atorvastatin) was an
      independent predictor of residual serum TXB2 levels, and the percentage of
      patients with enhanced values was significantly lower in statin users vs.
      nonusers. We provide evidence in vitro that atorvastatin reduced residual TXB2
      generation by increasing the extent of acetylation of platelet COX-1 by aspirin.
      In conclusion, the coadministration of statins may counter the mechanisms
      associated with reduced bioavailability of aspirin detected in some individuals
      with CV disease.

PMID- 29574793
TI  - Identifying Human Naive Pluripotent Stem Cells - Evaluating State-Specific
      Reporter Lines and Cell-Surface Markers.
AB  - Recent reports that human pluripotent stem cells can be captured in a spectrum of
      states with variable properties has prompted a re-evaluation of how pluripotency
      is acquired and stabilised. The latest additions to the stem cell hierarchy open
      up opportunities for understanding human development, reprogramming, and cell
      state transitions more generally. Many of the new cell lines have been
      collectively termed 'naive' human pluripotent stem cells to distinguish them from
      the conventional 'primed' cells. Here, several transcriptional and epigenetic
      hallmarks of human pluripotent states in the recently described cell lines are
      reviewed and evaluated. Methods to derive and identify human naive pluripotent
      stem cells are also discussed, with a focus on the uses and future developments
      of state-specific reporter cell lines and cell-surface proteins. Finally,
      opportunities and uncertainties in naive stem cell biology are highlighted, and
      the current limitations of human naive pluripotent stem cells considered,
      particularly in the context of differentiation.

PMID- 29574794
TI  - Acromegalic cardiomyopathy: Epidemiology, diagnosis, and management.
AB  - Acromegalic cardiomyopathy is the leading cause of morbidity and all-cause
      mortality in patients with acromegaly. Though acromegaly is a rare condition, the
      associated derangements are vast and severe. Stemming from an increase in
      circulating growth hormone (GH) and insulin-like growth factor-1 levels (IGF-1),
      acromegalic cardiomyopathy results in pathological changes in myocyte growth and
      structure, cardiac contractility, and vascular function. These molecular changes
      manifest commonly as biventricular hypertrophy, diastolic and systolic
      dysfunction, and valvular regurgitation. Early recognition of the condition is
      paramount, though the insidious progression of the disease commonly results in a
      late diagnosis. Biochemical testing, based on IGF-1 measurements, is the gold
      standard of diagnosis. Management should be centered on normalizing serum levels
      of both IGF-1 and GH. Transsphenoidal resection remains the most cost-effective
      and permanent treatment for acromegaly, though medical therapy possesses benefit
      for those who are not surgical candidates. Ultimately, achieving control of
      hormone levels results in a severe reduction in mortality rate, underscoring the
      importance of early recognition and treatment.

PMID- 29574795
TI  - In-vitro evaluation of accuracy of dynamic contrast-enhanced ultrasound (DCEUS)
      based parametric perfusion imaging with respiratory motion-compensation.
AB  - PURPOSE: The accuracy of multi-parametric perfusion imaging (PPI) based on
      dynamic contrast-enhanced ultrasound is disturbed by the respiratory motion in
      some cases, especially during characterizing hemodynamic features of abdominal
      tumor angiogenesis. This study aimed to effectively remove those disturbances on
      PPI and evaluate its accuracy. METHOD: The respiratory motion-compensation
      (rMoCo) strategy in PPI was modified by employing non-negative matrix
      factorization combined with phase-by-phase compensation. According to the known
      and controllable ground truths in in-vitro perfusion experiments, the accuracy of
      the modified rMoCo strategy was further evaluated from multiple perspectives in a
      simulated dual-vessel flow phantom. RESULTS: Compared with that of PPIs without
      rMoCo, the mean correlation coefficient between six PPIs with rMoCo and the
      corresponding static PPIs was up to 0.98 +/- 0.01 and improved by 0.17 +/- 0.04
      (P < 0.05). The estimated error of vascular diameter decreased from 87.85% (P <
      0.05) to 7.25% (P < 0.05) after rMoCo. PPIs with rMoCo were significantly
      consistent with static PPIs without respiratory motion disturbances. CONCLUSIONS:
      These quantitative results illustrated the disturbances induced by respiratory
      motion were effectively removed and the accuracy of PPIs was significantly
      improved. The partial parabolic and bimodal hemodynamic characteristics and the
      anatomical structures and sizes were accurately quantified and depicted by PPIs
      with rMoCo. The modified method can benefit physicians in providing accurate
      diagnoses and in developing appropriate therapeutic strategies for abdominal
      diseases.

PMID- 29574796
TI  - Low-cost biotransformation of glycerol to 1,3-dihydroxyacetone through
      Gluconobacter frateurii in medium with inorganic salts only.
AB  - : Existing dihydroxyacetone (DHA) production practices require the use of yeast
      extracts, leading to relatively high production costs. This study explores the
      use of low-cost media comprising glycerol, inorganic salts and Gluconobacter
      frateurii BCC 36199 in the production of DHA. The medium components are also
      quantitatively optimized. Regression models describing the linear correlations
      between the nutrient concentrations and the generated DHA concentration (p), and
      between the nutrient concentrations and the yield (ysp ) are developed. Under the
      optimal conditions according to our regression models, the highest values for p
      and ysp are 29.36 g l-1 and 97.86% g g-1 respectively. Quantitatively, this study
      shows positive effects of inorganic salts and adverse effects of excessive
      amounts of glycerol on DHA production. In particular, the results suggest that
      low levels of biomass production lead to high levels of DHA production.
      Consequently, the media containing inorganic nitrogen source from (NH4 )2 SO4
      lead to higher yields than organic media containing yeast extract. This study has
      identified an optimal, low-cost, minimal medium that can effectively enhance DHA
      production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study illustrates the
      advantages of inorganic nutrients supplementation over organic nutrient
      supplementation for a lower media cost and a higher dihydroxyacetone (DHA)
      production yield through Gluconobacter frateurii BCC 36199 cultivation. The study
      found that the use of media that contain only glycerol and inorganic salts
      enhanced DHA production (DHA-Prod) while keeping the production of bacterial
      biomass at a sufficient level. Most of the starting material, that is, glycerol,
      is converted into DHA, which is the target of the production process. The cost of
      the nitrogen supplement in the DHA-Prod process may be reduced by up to 80%
      through the use of the inorganic culture medium that has been developed in this
      study.

PMID- 29574797
TI  - The antimalarial compound ELQ-400 is an unusual inhibitor of the bc1 complex,
      targeting both Qo and Qi sites.
AB  - Inhibitors of the mitochondrial respiratory chain cytochrome bc1 complex, such as
      the antimalarial atovaquone and ELQ-300, and many well-studied compounds, are
      classified as either Qo or Qi site inhibitors based on their site of action.
      Here, we investigated the site of action of ELQ-400 that showed an unusual
      behaviour, being effective against parasites resistant to the Qo  site inhibitor
      atovaquone or to the Qi site inhibitor ELQ-300. Analysis of yeast mutants and
      comparison with atovaquone and other ELQs strongly suggest that ELQ-400 targets
      both Qo  and Qi  sites. Dual site inhibition would be particularly efficient as
      it would lower the risk of acquired resistance. However, such compounds are
      seldom found, which could be explained by structural and mechanistic differences
      between the sites.

PMID- 29574798
TI  - Modulation of human dendritic cell activity by Giardia and helminth antigens.
AB  - Giardia duodenalis is a common intestinal protozoan parasite known to modulate
      host immune responses, including dendritic cell (DC) function. Coinfections of
      intestinal pathogens are common, and thus, DCs may be concurrently exposed to
      antigens from multiple parasites. Here, we investigated the effects of G.
      duodenalis products on human monocyte-derived DC function independently and in
      combination with helminth antigens (Ascaris suum and Trichuris suis). All
      antigens individually induced an anti-inflammatory phenotype in DCs, reducing
      lipopolysaccharide (LPS)-induced interleukin (IL)-6, IL-12p70 and tumour necrosis
      factor (TNF)-alpha secretion. G. duodenalis and T. suis products also
      consistently upregulated IL-10 production. Despite a similar modulation of
      cytokine secretion, additive effects between Giardia and helminth products were
      not observed, indicating a dominant effect of a single parasite stimulus and
      limited interactive effects on DC function. G. duodenalis trophozoites induced
      rapid apoptosis in DCs, which was not observed with the helminth antigens
      suggesting that the modulatory effects of G. duodenalis may override that of A.
      suum and T. suis. Thus, G. duodenalis modulates DC activity by modulating
      cytokine secretion and/or inducing apoptosis, which may be a parasite-driven
      mechanism to dampen host immunity and establish chronic infections. The
      differential mechanisms of DC modulation by intestinal parasites warrant further
      attention.

PMID- 29574799
TI  - Eyebrow allergic contact dermatitis caused by m-aminophenol and toluene-2,5
      diamine secondary to a temporary black henna tattoo.

PMID- 29574800
TI  - High salt-induced excess reactive oxygen species production resulted in heart
      tube malformation during gastrulation.
AB  - An association has been proved between high salt consumption and cardiovascular
      mortality. In vertebrates, the heart is the first functional organ to be formed.
      However, it is not clear whether high-salt exposure has an adverse impact on
      cardiogenesis. Here we report high-salt exposure inhibited basement membrane
      breakdown by affecting RhoA, thus disturbing the expression of Slug/E-cadherin/N
      cadherin/Laminin and interfering with mesoderm formation during the epithelial
      mesenchymal transition(EMT). Furthermore, the DiI+ cell migration trajectory in
      vivo and scratch wound assays in vitro indicated that high-salt exposure
      restricted cell migration of cardiac progenitors, which was caused by the weaker
      cytoskeleton structure and unaltered corresponding adhesion junctions at HH7.
      Besides, down-regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up-regulation
      of Wnt3a/beta-catenin caused aberrant cardiomyocyte differentiation at HH7 and
      HH10. High-salt exposure also inhibited cell proliferation and promoted
      apoptosis. Most importantly, our study revealed that excessive reactive oxygen
      species(ROS)generated by high salt disturbed the expression of cardiac-related
      genes, detrimentally affecting the above process including EMT, cell migration,
      differentiation, cell proliferation and apoptosis, which is the major cause of
      malformation of heart tubes.

PMID- 29574801
TI  - Prevalence and characteristics of hair plucking in captive bonobos (Pan paniscus)
      in North American zoos.
AB  - When primates exhibit hair loss and are observed to engage in self or social hair
      plucking (a rapid jerking away of the hair shaft and follicle by the hand or
      mouth, often accompanied by inspection, and consumption) the altered appearance,
      and behavior patterns are thought to reflect individual physiological, and
      psychological well-being. Hair loss and hair plucking occur in many captive
      primate species, including all of the great apes. We present the first survey of
      this behavior among captive bonobos (N = 88; 50 females and 38 males) in seven
      zoos in the United States. We found that 43% of the population engaged in this
      behavior pattern and discounting youngsters (who are not observed to hair pluck
      until the age of five), 58% of individuals hair plucked. Of the individuals who
      hair plucked, 97% engaged in social plucking, whereas 46% engaged in self
      directed plucking. We regressed the occurrence of hair plucking with multiple
      predictor variables using binary logistic regression and multimodel inference to
      determine which predictors best explained the prevalence of self-directed and
      social plucking. We also analyzed publicly available data on hair plucking in
      captive chimpanzees. We found that the occurrence of another abnormal behavior,
      age, origin, and pelage condition best explained self-directed plucking in
      bonobos. Social plucking was explained by age, origin, pelage, and sex. Our
      analysis of chimpanzee hair plucking revealed that plucking is strongly
      influenced by rearing and sex. This study demonstrates that hair plucking is more
      prevalent in captive bonobos compared to captive chimpanzees and gorillas,
      however, the covariates associated with hair plucking for each species are
      different. Our data suggest a potential link between self-directed plucking and
      well-being. However, the higher prevalence and etiology of social hair plucking
      is more difficult to explain.

PMID- 29574802
TI  - Plant stem cells and de novo organogenesis.
AB  - Contents Summary 1334 I. Introduction 1334 II. Regeneration-initial cell: the
      origin of regeneration 1335 III. Acquiring regeneration competency: the essential
      intermediate step for hormone-induced regeneration 1335 IV. Hormonal induction of
      stem cell regulators: the program for de novo establishment of apical meristems
      1337 V. Conclusions and perspectives 1337 Acknowledgements 1338 Author
      contributions 1338 References 1338 SUMMARY: High cellular plasticity confers
      remarkable regeneration capacity to plants. Based on the activity of stem cells
      and their regulators, higher plants are capable of regenerating new individuals.
      De novo organogenesis exemplifies the regeneration of the whole plant body and is
      exploited widely in agriculture and biotechnology. In this Tansley insight
      article, we summarize recent advances that facilitate our understanding of the
      molecular mechanisms underlying de novo organogenesis. According to our current
      knowledge, this process can be divided into three steps, including activation of
      regeneration-initial cells, acquisition of competency and de novo establishment
      of apical meristems. The functions of stem cells and their regulators are
      critical to de novo organogenesis, whereas auxin and cytokinin act as triggers
      and linkers between different steps.

PMID- 29574803
TI  - Preventive effect of polynucleotide on post-thyroidectomy scars: A randomized,
      double-blinded, controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Polynucleotide (PN) provides a structural scaffold to
      induce anti-inflammatory and enhanced wound healing properties, and this study
      aimed to assess the efficacy of PN administration in the prevention of post
      operative scars after conventional open total thyroidectomy. STUDY DESIGN
      MATERIALS AND METHODS: Forty-two patients with thyroid carcinoma who underwent
      total thyroidectomy were randomly assigned to the study (PN administration) or
      control (normal saline) group. All patients underwent a single session of
      combined ablative and non-ablative fractional laser. The Vancouver Scar Scale
      (VSS), global photographic assessment, and objective scar were assessed using
      three-dimensional (3D) camera at baseline and at 2, 4, 8, and 16 weeks after
      surgery. RESULTS: Patients who underwent PN injection demonstrated better
      surgical scar quality outcome. Participants in the PN administration group had
      lower VSS scores than the control group (2.09 +/- 0.47 vs. 4.01 +/- 0.55,
      respectively) and lower scar height (0.23 +/- 0.03 vs. 0.29 +/- 0.03,
      respectively), as measured using 3D imaging. Furthermore, in the PN injected
      group, the degree of erythema, and pigmentation of the scar were less prominent.
      No patient developed hypertrophic scar or keloids on the surgical site. No other
      adverse events, including post-inflammatory hyperpigmentation, scarring, or
      infection, were observed. CONCLUSION: Adjuvant administration of PN along with
      conventional fractional laser treatment led to more favorable effect in wound
      healing and post-operative scar prevention after thyroidectomy. Lasers Surg. Med.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29574804
TI  - Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers
      and pulmonary function tests in patients with sulphur mustard-induced lung
      disorders: A randomized double-blind clinical trial.
AB  - WHAT IS KNOWN AND OBJECTIVE: In this study, the effect of carvacrol (CAR) on
      pulmonary function tests (PFT), haematological indices and oxidant/antioxidant
      biomarkers in patients with sulphur mustard (SM)-induced lung disorders was
      examined. METHODS: Twenty patients exposed to SM 27-30 years ago were divided
      into two groups and treated with either placebo (P) or CAR (1.2 mg/kg per day) (n
      = 10 for each group). Forced vital capacity (FVC), peak expiratory flow (PEF),
      total and different white blood cell (WBC), haematological parameters and
      oxidant/antioxidant biomarkers were measured at the baseline (step 0), one and
      two months (steps I and II, respectively) after starting the treatment. RESULTS
      AND DISCUSSION: PEF was significantly increased in the CAR-treated group in step
      II compared to step 0 (P < .01). Total WBC (P < .01) and neutrophil (P < .05)
      count in the CAR-treated group were significantly decreased in the group in steps
      I and II (P < .01 for both cases) compared to step 0. The levels of thiol,
      superoxide dismutase and catalase in the CAR-treated group were significantly
      increased (P < .05 to P < .001) in steps I and II, but malondialdehyde
      significantly decreased in step II compared to step 0 (P < .01). The percentage
      of total and differential WBC, oxidant/antioxidant biomarkers, FVC and PEF values
      following a two-month treatment period were significantly improved in the CAR
      treated group compared to the placebo group (P < .05 to P < .001). WHAT IS NEW
      AND CONCLUSION: Two-month treatment with CAR reduced inflammatory cells and
      oxidant biomarkers, whereas increased antioxidant biomarkers and improved PFT
      tests in SM-exposed patients.

PMID- 29574805
TI  - Investigation of the Relationship Between Electrical Stimulation Frequency and
      Muscle Frequency Response Under Submaximal Contractions.
AB  - Neuromuscular electrical stimulation (NMES) is a common tool that is used in
      clinical and laboratory experiments and can be combined with mechanomyography
      (MMG) for biofeedback in neuroprostheses. However, it is not clear if the
      electrical current applied to neuromuscular tissues influences the MMG signal in
      submaximal contractions. The objective of this study is to investigate whether
      the electrical stimulation frequency influences the mechanomyographic frequency
      response of the rectus femoris muscle during submaximal contractions. Thirteen
      male participants performed three maximal voluntary isometric contractions (MVIC)
      recorded in isometric conditions to determine the maximal force of knee
      extensors. This was followed by the application of nine modulated NMES
      frequencies (20, 25, 30, 35, 40, 45, 50, 75, and 100 Hz) to evoke 5% MVIC. Muscle
      behavior was monitored by the analysis of MMG signals, which were decomposed into
      frequency bands by using a Cauchy wavelet transform. For each applied electrical
      stimulus frequency, the mean MMG spectral/frequency response was estimated for
      each axis (X, Y, and Z axes) of the MMG sensor with the values of the frequency
      bands used as weights (weighted mean). Only with respect to the Z (perpendicular)
      axis of the MMG signal, the stimulus frequency of 20 Hz did not exhibit any
      difference with the weighted mean (P = 0.666). For the frequencies of 20 and 25
      Hz, the MMG signal displayed the bands between 12 and 16 Hz in the three axes (P
      < 0.050). In the frequencies from 30 to 100 Hz, the muscle presented a higher
      concentration of the MMG signal between the 22 and 29 Hz bands for the X and Z
      axes, and between 16 and 34 Hz bands for the Y axis (P < 0.050 for all cases). We
      observed that MMG signals are not dependent on the applied NMES frequency,
      because their frequency contents tend to mainly remain between the 20- and 25-Hz
      bands. Hence, NMES does not interfere with the use of MMG in neuroprosthesis.

PMID- 29574806
TI  - Intercountry master's degree in nursing: policy implications for the Mozambican
      health system.
AB  - PURPOSE: Within an overarching evaluation framework, this study explored the
      experiences of course participants and administrators of an intercountry master's
      degree in nursing between South Africa and Mozambique. The lessons learnt were
      used to inform nursing and health policy for the Mozambican health system.
      METHODS: Kirkpatrick's four levels of training evaluation and a results-oriented
      approach to capacity change were integrated to form a hybrid evaluation framework
      to capture information about course implementation and the context/environment
      within which it was delivered. The study used quantitative and qualitative
      methods including a self-administered survey of course participants, document
      review, in-depth, semi-structured interviews with course administrators and two
      focus group discussions with course participants. FINDINGS: Participants enrolled
      in the course primarily to gain new knowledge and to improve health outcomes;
      course participants and administrators responded positively to the course design,
      course implementation and the quality of teaching. Knowledge and skills gained
      help to build graduates' confidence and boost their attitude towards nursing.
      Paradoxically, graduates felt powerless to transfer knowledge and effect change
      in practice. CONCLUSION: This collaborative, capacity development project
      produced postgraduate nurses in two areas of specialization, namely, critical
      care and trauma nursing and maternal and neonatal health. While course
      participants gained significant benefits in new skills and knowledge and a higher
      degree qualification, the rewards available to them in the public health system
      remain unclear. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Lessons learnt may
      serve to influence policy decisions about the role of the Ministry of Health and
      other stakeholders in sustaining the output and quality of postgraduate nurses
      for the Mozambican health system. A strategic approach informed by multilevel
      policies at government, organizational and managerial levels should be adopted to
      systematically minimize and remove barriers to the transfer and utilization of
      knowledge and skills in the workplace.

PMID- 29574808
TI  - Oral Cancer.
AB  - The management of oral cancer is a multidisciplinary endeavour, as each patient
      presents the treating clinicians with a unique set of challenges the management
      of which impacts on both survival and quality of life. This article focuses on
      the management of oral cancer. We highlight the epidemiology and risk factors for
      oral cancer in Australia, the various clinical presentations that occur and the
      staging of oral cancer. In the vast majority of cases surgery remains the
      mainstay of treatment. Radiation and medical oncology is usually used in an
      adjuvant context. Dental professionals play a critical role in many stages of
      management from the initial detection, to optimising pre treatment dental health
      and managing the short and long term sequelae of treatment. Monitouring for
      recurrence and the development of second primary tumours is a key role.

PMID- 29574807
TI  - A glycosyl transferase family 43 protein involved in xylan biosynthesis is
      associated with straw digestibility in Brachypodium distachyon.
AB  - The recalcitrance of secondary plant cell walls to digestion constrains biomass
      use for the production of sustainable bioproducts and for animal feed. We
      screened a population of Brachypodium recombinant inbred lines (RILs) for cell
      wall digestibility using commercial cellulases and detected a quantitative trait
      locus (QTL) associated with this trait. Examination of the chromosomal region
      associated with this QTL revealed a candidate gene that encodes a putative
      glycosyl transferase family (GT) 43 protein, orthologue of IRX14 in Arabidopsis,
      and hence predicted to be involved in the biosynthesis of xylan. Arabinoxylans
      form the major matrix polysaccharides in cell walls of grasses, such as
      Brachypodium. The parental lines of the RIL population carry alternative
      nonsynonymous polymorphisms in the BdGT43A gene, which were inherited in the RIL
      progeny in a manner compatible with a causative role in the variation in straw
      digestibility. In order to validate the implied role of our candidate gene in
      affecting straw digestibility, we used RNA interference to lower the expression
      levels of the BdGT43A gene in Brachypodium. The biomass of the silenced lines
      showed higher digestibility supporting a causative role of the BdGT43A gene,
      suggesting that it might form a good target for improving straw digestibility in
      crops.

PMID- 29574809
TI  - The contemporary management of third molars.
AB  - The management of third molars requires a significant assessment and decision
      process both for the patient and the clinician. The clinician must always
      identify the indication for third molar surgery, assess the risks of the proposed
      procedure, and then modify their plan to account for the patient's current and
      future health, their social and financial setting, and the patient's tolerance of
      risk. In doing this, the clinician can tailor a solution to meet the individual
      patient's needs. This decision to remove a third molar is made in the fluid
      setting of the patient's quality of life and requires regular review. This
      article gives the clinician the tools, the matrix, and the confidence to guide
      patients through this process, and outlines some of the pitfalls and common
      points of bias within the process.

PMID- 29574810
TI  - Management of temporomandibular joint disorders: A surgeon's perspective.
AB  - Disorders of the Temporomandibular joint (TMJ) may clinically present with jaw
      pain and restricted mouth opening that may limit a patient's access to
      comprehensive dental care. The aim of this article is to provide a general
      overview of the current treatment strategies available in the management of
      disorders of the TMJ. Both conservative and surgical treatment options will be
      discussed as there is no one treatment for temporomandibular disorders (TMD)
      which encompasses a wide range of diagnoses. A multidisciplinary team approach to
      management is essential in the fundamental care of all TMD patients so that
      treatment can be specifically tailored to individual patient needs.

PMID- 29574811
TI  - Contemporary exodontia.
AB  - Exodontia is a cardinal skill of all dentists. Patients expect extractions to be
      skillfully and painlessly accomplished every time. It's not necessarily so simple
      and can be challenging. In this paper we explore contemporary issues of the full
      process of exodontia including diagnosis, technique, complication minimization as
      well as management of medically compromised patients with appropriate post
      operative care, including pharmacotherapy.

PMID- 29574812
TI  - The teaching of oral & maxillofacial surgery to dental students in Australia &
      New Zealand.
AB  - The teaching of OMS to dental students in Australia & New Zealand was surveyed.
      Generally the established schools had well developed curricula with good didactic
      and clinical experience conducted by specialist OMS educators. There was a much
      greater array of teaching in some of the newer schools with some appearing to
      barely meet the current minimalist professional competencies of the ADC. The
      critical element was whether or not the school was associated with a speciality
      OMS Unit at a Teaching Hospital. Proposals addressing these deficiencies are
      presented.

PMID- 29574813
TI  - Paediatric oral & maxillofacial surgery.
AB  - Children have differences in their physiology, anatomy and they are continuing to
      grow and develop. The management of pathology, trauma, deformity and upper airway
      obstruction in the young growing patient has to take into account these factors
      in the treatment planning for these conditions. It is important for Oral &
      Maxillofacial Surgeons to understand the potential impact of disease or injury on
      the developing facial skeleton and dentition. This chapter will provide an
      overview of the some of the major components of paediatric maxillofacial surgery
      and their management.

PMID- 29574815
TI  - Reconstruction of major defects of the jaws.
AB  - Prosthetic replacements in the 19th and early 20th century were superseded by
      pedicled flaps and obturators. These have subsequently been superseded by free
      tissue transfer which currently is the mainstay of reconstructive jaw surgery.
      Although malignant and benign processes of the jaws are the predominant cause of
      segmental defects, a significant proportion still occurs due to trauma, or even
      iatrogenic causes such as radiotherapy. The varied aetiologies demand a nuanced
      approach to reconstruction and although the techniques remain similar the timing
      can be quite different. The maxilla and the mandible are both amenable to
      composite reconstruction with bone. The fibula, iliac crest, scapula, distal
      radius and medial femoral condyle are the most commonly utilised donor sites for
      vascularised reconstruction. Each has strengths and weaknesses and the
      requirements of the defect, and patient preference should outweigh surgeon
      preference. Osseointegrated implants allow reliable rehabilitation of the
      dentition by anchoring facial prostheses. Their integration into composite flaps
      is highly reliable although soft tissue management can be challenging. Virtual
      surgical planning and 3D printing have already impacted on the surgical workflow
      and improved the reliability and accuracy of results. If this technology can be
      applied to tissue typing and human tissue (instead of just plastic and metal) a
      fully prefabricated and vascularised jaw without donor site morbidity would be
      the ultimate aim.

PMID- 29574814
TI  - Extractions to reconstruction: The Development of Oral & Maxillofacial Surgery in
      Australian and New Zealand.
AB  - Oral and Maxillofacial Surgery developed initially from Dentistry as exodontia.
      It then expanded into the surgical management of jaw disorders. As the specialty
      evolved, it came into increasing conflict with related surgical disciplines. In
      the 1960s and 1970s these external criticisms were well-founded as training in
      oral surgery was individual, solely University-based and highly variable. In the
      1980s the speciality developed a plan which involved hospital-based surgical
      training, a mandatory high level college surgical examination and detailed
      workforce and training studies. These were progressively implemented over the
      next twenty years with a dual degree (medicine and dentistry) and a final
      fellowship (FRACDS (OMS)). This resulted in accreditation by the Australian
      Medical Council and the Australian Dental Council and recognition as a Principal
      Surgical Speciality by the Commonwealth Department of Health. This development
      was monitored by published workforce studies over three decades that are
      important yardsticks to inform the credentialing of dental specialists.

PMID- 29574816
TI  - Current and evolving trends in the management of facial fractures.
AB  - The oral and maxillofacial region has a complex regional anatomy including hard
      and soft tissues. Trauma in this region may affect the airway, cause potentially
      life threatening bleeding and head injuries. The senses of olfaction, sight and
      hearing can also be disrupted as well as a profound psychological impact
      following disfigurement. This oral and maxillofacial trauma update provides
      information on demographics, incidence, pathophysiology, diagnosis, fracture
      patterns and management of facial trauma. It also discusses the role of new
      advancements in the management of facial trauma.

PMID- 29574817
TI  - Craniofacial disorders.
AB  - The complexity of the craniofacial patient mandates the cooperation of a
      multidisciplinary team that can systematically evaluate each individual and
      ensure that a protocol-driven pathway is undertaken for the best patient care.
      Oral and maxillofacial surgeons contribute to surgical care in this setting with
      specific knowledge of growth and development of the face. This enables optimum
      timing for early skeletal correction where appropriate, and definitive surgery
      following the cessation of growth to maximize function and aesthetics. This
      chapter will describe the major principles in managing patients with specific
      craniofacial anomalies and provide examples of the outcomes possible.

PMID- 29574818
TI  - Guest Editorial Contemporary Oral & Maxillofacial Surgery.

PMID- 29574819
TI  - Implant based rehabilitation options for the atrophic edentulous jaw.
AB  - The atrophic and edentulous jaw can pose a number of challenges for the implant
      clinician. In simple terms, the amount of bone that remains is insufficient for
      the conventional placement of a dental implant. A variety of treatment strategies
      can be employed to enable implants to be placed despite the paucity of bone stock
      in either the mandible or the maxilla. Conceptually these strategies follow one
      of two pathways: either augmentation of the bone, or the novel utilization of the
      remaining bone. This article will discuss patient assessment, treatment planning,
      and the range of contemporary options available to enable fixed implant based
      rehabilitation of each jaw. "The edentulous patient is an amputee, an oral
      invalid, to whom we should pay total respect and rehabilitation ambitions" (P-I
      Branemark, September 2005).

PMID- 29574820
TI  - Implantology in oral & maxillofacial surgery. The complexity of 'simple' cases.
AB  - Dental implants have been a routine part of dental practice for many years and
      are performed by a variety of practitioners with different backgrounds and
      training. This paper will outline the principles and practical surgical aspects
      of 'simple' implant placement against a background of our current understanding
      of the literature that informs our surgical procedures. Implants need to be
      placed in a restoratively suitable position surrounded by sufficient bone, draped
      in adequate keratinised soft tissue and sufficiently separated from one another
      and the adjacent teeth. Practically, while the above principles apply, there are
      nuances based on the local situation, adjacent teeth and restorative needs which
      will be considered in this paper. Surgery for the placement of implants needs a
      practitioner with adequate surgical training and experience and who understands
      the biological aspects and restorative needs of each clinical situation.

PMID- 29574821
TI  - Versatile facial osteotomies.
AB  - Facial Osteotomy techniques have evolved enormously over the past 20 years
      providing significant and often life-changing benefits to our dental patients
      with skeletal malocclusions. Advancements in technology and refined surgical
      techniques have resulted in improvements in surgical outcomes, a reduction in
      post-operative complications and a quicker recovery for today's patients
      undergoing orthognathic surgery. This paper aims to an update on the contemporary
      approach to the correction of skeletal malocclusions with facial osteotomies.

PMID- 29574822
TI  - Balancing the benefits of intrathecal baclofen pump surgery with potential
      postoperative complications.

PMID- 29574823
TI  - Active matrix metalloproteinase-8 and periodontal bacteria-interlink between
      periodontitis and inflammatory bowel disease?
AB  - BACKGROUND: The aim of this study was the investigation of concentration and
      prevalence of selected periodontal pathogenic bacteria and concentration of
      active matrix metalloproteinase-8 (aMMP-8) within a group of patients with
      inflammatory bowel diseases (IBD) and to compare the results with a group of
      healthy control subjects (HC). METHODS: Fifty-nine IBD patients with Crohn's
      disease (CD, n = 30) or ulcerative colitis (UC, n = 29) and 59 HC were included
      in this cross-sectional study. Based on periodontal probing depth (PD) and
      clinical attachment level (CAL), periodontitis was classified as healthy/mild,
      moderate, or severe. aMMP-8 was analyzed from gingival crevicular fluid using
      enzyme linked immunosorbent assay. Eleven selected periodontal pathogenic
      bacteria were analyzed in subgingival plaque samples using polymerase chain
      reaction. RESULTS: IBD patients showed higher CAL (P < 0.01), more severe
      periodontitis (P = 0.04), gingival bleeding (P < 0.01) and aMMP-8 concentration
      (P < 0.01) than HC. Only in CD, increasing severity of periodontitis was
      associated with an increase in aMMP-8 concentration (P = 0.02). The prevalences
      of Eubacterium nodatum and Eikenella corrodens were significantly lower in IBD
      compared to HC (P = 0.01). Additionally, the prevalence of Eikenella corrodens
      was significantly higher in CD compared to the UC group (P = 0.04). Further
      statistically significant differences in selected bacteria between IBD and HC or
      CD and UC groups could not be found (P > 0.05). CONCLUSIONS: The results reveal
      changes in host immune response of IBD patients in terms of aMMP-8. Only in CD
      increasing aMMP-8 was associated with severity of periodontal disease. The role
      of periodontal pathogenic bacteria in the interrelationship between IBD and
      periodontitis remains unclear.

PMID- 29574824
TI  - An LC-MS/MS method for quantification of demethylzeylasteral, a novel
      immunosuppressive agent in rat plasma and the application to a pharmacokinetic
      study.
AB  - In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was developed and validated for the quantification of
      demethylzeylasteral in rat plasma. Electrospray ionization was operated in the
      negative ion mode while demethylzeylasteral and oleanolic acid (internal
      standard) were measured by selected reaction monitoring (demethylzeylasteral: m/z
      479.2 -> 436.0; oleanolic acid: m/z 454.9 -> 407.2). This LC-MS/MS method had
      good selectivity, sensitivity, accuracy and precision. The pharmacokinetic
      profiles of demethylzeylasteral were subsequently examined in Wistar rats after
      oral or intravenous administration.

PMID- 29574825
TI  - Risk factors associated with allergic sensitization and asthma phenotypes among
      poultry farm workers.
AB  - BACKGROUND: This study investigated the risk factors for occupational allergic
      sensitization and various asthma phenotypes in poultry-workers. METHODS: A cross
      sectional study of 230 workers used a modified ECRHS questionnaire, spirometry,
      FeNO, Phadiatop, and sIgE to poultry farming related allergens. RESULTS: Worker's
      mean age was 37 +/- 9 years, 68% male, 43% current-smokers, 34% atopic, and 5%
      casual-workers. The prevalence of non-atopic asthma (NAA = 7%) was higher than
      atopic-asthma (AA = 5%) and probable allergic occupational-asthma (OA = 3%).
      Sensitization to at least one poultry farming related allergen was 24%. Workers
      sensitized to chicken-specific-allergens were more likely to be atopic (ORunadj 
      = 20.9, 95%CI: 4.7-93.2) or employed as casual-workers (ORunadj  = 6.0, 95%CI:
      1.1-35.9). Work-related chest symptoms were associated the rearing-department
      (ORadj  = 3.2, 95%CI: 1.2-8.4) and exposure to high gas/dust/fumes (ORadj  = 4.8,
      95%CI: 2.4-9.5). Airflow reversibility (ORadj  = 10.9, 95%CI: 2.0-60.3) was
      significantly associated with casual-work status. CONCLUSION: Allergic and non
      allergic mechanisms play a role in asthma development among poultry-workers with
      casual workers demonstrating increased risk.

PMID- 29574827
TI  - Addressing the estimation of standard errors in fixed effects meta-analysis.
AB  - Standard methods for fixed effects meta-analysis assume that standard errors for
      study-specific estimates are known, not estimated. While the impact of this
      simplifying assumption has been shown in a few special cases, its general impact
      is not well understood, nor are general-purpose tools available for inference
      under more realistic assumptions. In this paper, we aim to elucidate the impact
      of using estimated standard errors in fixed effects meta-analysis, showing why it
      does not go away in large samples and quantifying how badly miscalibrated
      standard inference will be if it is ignored. We also show the important role of a
      particular measure of heterogeneity in this miscalibration. These developments
      lead to confidence intervals for fixed effects meta-analysis with improved
      performance for both location and scale parameters.

PMID- 29574828
TI  - Functional morphology in the pages of the AJPA.

PMID- 29574826
TI  - Antibody repertoire analysis in polygenic autoimmune diseases.
AB  - High-throughput sequencing of the DNA/RNA encoding antibody heavy- and light
      chains is rapidly transforming the field of adaptive immunity. It can address key
      questions, including: (i) how the B-cell repertoire differs in health and
      disease; and (ii) if it does differ, the point(s) in B-cell development at which
      this occurs. The advent of technologies, such as whole-genome sequencing, offers
      the chance to link abnormalities in the B-cell antibody repertoire to specific
      genomic variants and polymorphisms. Here, we discuss the current research using B
      cell antibody repertoire sequencing in three polygenic autoimmune diseases where
      there is good evidence for a pathological role for B-cells, namely systemic lupus
      erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune
      diseases exhibit significantly skewed B-cell receptor repertoires compared with
      healthy controls. Interestingly, some common repertoire defects are shared
      between diseases, such as elevated IGHV4-34 gene usage. B-cell clones have
      effectively been characterized and tracked between different tissues and blood in
      autoimmune disease. It has been hypothesized that these differences may signify
      differences in B-cell tolerance; however, the mechanisms and implications of
      these defects are not clear.

PMID- 29574829
TI  - A sort of revolution: Systematics and physical anthropology in the 20th century.
AB  - During the first four decades of the 20th century, a system of ideas about the
      evolution and systematics of humans and other primates coalesced around the work
      of George Gaylord Simpson and W. E. Le Gros Clark. Buttressed by the "new
      physical anthropology" of the 1950s, that system provided an authoritative model
      a disciplinary matrix or paradigm-for the practice of that aspect of biological
      anthropology. The Simpson-Le Gros Clark synthesis began to unravel in the 1960s
      and collapsed in the 1970s under the onslaught of cladistic systematics. The
      cladistic "revolution" resembles a paradigm shift of the sort proposed by Thomas
      Kuhn because it was driven, not by new biological discoveries or theories, but by
      a change in aesthetics.

PMID- 29574830
TI  - Exceeding Hrdlicka's aims: 100 Years of genetics in anthropology.

PMID- 29574831
TI  - Race, then and now: 1918 revisited.

PMID- 29574832
TI  - Physical anthropology in 1918 and the founding of the U.S. journal.
AB  - In 1918, the first issue of the American Journal of Physical Anthropology was
      prepared and distributed by Ales Hrdlicka, the Curator of Physical Anthropology
      at the Smithsonian Institution. This was a singular act, both in the general and
      specific sense. It was the first journal of physical anthropology published in
      the United States, and it was a sole effort by Hrdlicka, who was committed to
      promoting and recognizing physical anthropology as a new science in America. On
      this 100th anniversary of the founding of the journal, Hrdlicka's efforts were
      successful: physical/biological anthropology is a strong and timely discipline
      that represents a major area of scientific research today.

PMID- 29574833
TI  - Primate social behavior.

PMID- 29574834
TI  - Centennial perspective on human adaptability.

PMID- 29574835
TI  - A history of forensic anthropology.
AB  - Forensic anthropology represents a dynamic and rapidly evolving complex
      discipline within anthropology and forensic science. Academic roots extend back
      to early European anatomists but development coalesced in the Americas through
      high-profile court testimony, assemblage of documented collections and focused
      research. Formation of the anthropology section of the American Academy of
      Forensic Sciences in 1972, the American Board of Forensic Anthropology in
      1977/1978 and other organizational advances provided important stimuli for
      progress. While early pioneers concentrated on analysis of skeletonized human
      remains, applications today have expanded to include complex methods of search
      and recovery, the biomechanics of trauma interpretation, isotopic analysis
      related to diet and region of origin, age estimation of the living and issues
      related to humanitarian and human rights investigations.

PMID- 29574836
TI  - Demographic anthropology.

PMID- 29574837
TI  - Human life course biology: A centennial perspective of scholarship on the human
      pattern of physical growth and its place in human biocultural evolution.

PMID- 29574838
TI  - Nonhuman Primate Locomotion.

PMID- 29574840
TI  - One hundred years of paleoanthropology: An American perspective.

PMID- 29574841
TI  - Reflections on nutrition in biological anthropology.

PMID- 29574842
TI  - Dental anthropology in the AJPA: Its roots and heights.

PMID- 29574839
TI  - A century of development.

PMID- 29574843
TI  - The evolution of physical anthropology.

PMID- 29574844
TI  - Ethics in biological anthropology.

PMID- 29574846
TI  - Bioarchaeology in perspective: From classifications of the dead to conditions of
      the living.

PMID- 29574845
TI  - Hunter-gatherer studies and human evolution: A very selective review.
AB  - The century long publication of this journal overlapped major changes in the
      sciences it covers. We have been eyewitnesses to vast changes during the final
      third of the last century and beginning of this one, momentous enough to
      fundamentally alter our work separately and collectively. One (NBJ) from animal
      ethology, another from western North American archaeology (JOC), and a third (KH)
      from cultural anthropology came to longtime collaboration as evolutionary
      ecologists with shared focus on studying modern hunter-gatherers to guide
      hypotheses about human evolution. Our findings have radically revised hypotheses
      each of us took for granted when we began. Our (provisional) conclusions are not
      the consensus among hunter-gatherer specialists; but grateful that personal
      reflections are invited, we aim to explain how and why we continue to bet on
      them.

PMID- 29574847
TI  - The tales genes tell (or not): A century of exploration.

PMID- 29574848
TI  - 100 years of primate paleontology.

PMID- 29574849
TI  - A century of paleopathology.

PMID- 29574850
TI  - Genetic diagnosis of familial hypercholesterolemia is associated with a premature
      and high coronary heart disease risk.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant
      disease associated with premature coronary heart disease (CHD). Studies tend to
      show that patients with FH associated with an identified mutation (mutation+ FH)
      are at higher risk than patients without an identified mutation (mutation- FH).
      We compared the clinical and biological profile and the risk of CHD in patients
      with mutation+ FH and mutation- FH. HYPOTHESIS: In addition to LDL-C, a
      pathogenic mutation predicts premature CHD in FH. METHODS: We successively
      included all patients with suspected FH (LDL-C > 190 mg/dL if age > 18 years; LDL
      C > 160 mg/dL if age < 18 years) and compared patients with a pathogenic mutation
      with those without an identified pathogenic mutation. RESULTS: We studied 179
      patients with mutation+ FH and 147 with mutation- FH. The mean age was 44 (+/-
      18) years. The lipid profile was more atherogenic in those with mutation+ FH, who
      had higher LDL-C (254 +/- 69 mg/dL vs 218 +/- 35 mg/dL; P < 0.01) and lower HDL-C
      (53 +/- 14 mg/dL vs 58 +/- 17 mg/dL; P < 0.01). Despite the more atherogenic
      nonlipid cardiovascular profile of patients with mutation- FH, the age of CHD
      onset was earlier in patients with mutation+ FH (48 vs 56 years; P = 0.026).
      After multiple adjustment, the presence of a positive mutation was significantly
      associated with premature CHD (OR: 3.0, 95% CI: 1.38-6.55, P < 0.01).
      CONCLUSIONS: Patients with mutation+ FH have a more atherogenic lipid profile and
      a 3-fold higher risk of premature CHD, as well as earlier onset of CHD, than
      patients with mutation- FH.

PMID- 29574851
TI  - Dexmedetomidine-induced fever and delirium: A case report.
AB  - WHAT IS KNOWN AND OBJECTIVE: Dexmedetomidine is a selective alpha-2 agonist used
      for sedation in the intensive care unit (ICU). CASE DESCRIPTION: A 41-year-old
      woman intubated in the ICU and being treated for acute respiratory distress
      syndrome (ARDS) received dexmedetomidine following successful extubation to treat
      increasing agitation thought to be secondary to a history of polysubstance abuse.
      Following initiation of the dexmedetomidine, the patient became febrile as well
      as increasingly more agitated and delirious. All potential fever or delirium
      causes were evaluated. Following discontinuation of dexmedetomidine, her fever,
      agitation and delirium ceased. WHAT IS NEW AND CONCLUSION: We depict the first
      known case of dexmedetomidine causing high fevers and delirium.

PMID- 29574852
TI  - Early and late implant failure of submerged versus non-submerged implant healing:
      A systematic review, meta-analysis and trial sequential analysis.
AB  - INTRODUCTION: The aim of this systematic review was to analyse current evidence
      regarding differences in early and late implant failure as well as in marginal
      bone level (MBL) changes between submerged and non-submerged healed dental
      implants. METHODS: PUBMED, SCOPUS, EMBASE and Web of Science databases were
      searched for prospective randomized and non-randomized controlled studies
      addressing direct comparison between submerged and non-submerged implant healing,
      without performing immediate loading. Early and late implant failure (before or
      after 6 months from implant placement, respectively) together with MBL were the
      investigated outcomes. Risk of bias assessment was performed using the Cochrane
      Collaboration Tool for Randomized clinical trials. Meta-analysis was performed
      and the power of the meta-analytic findings determined by trial sequential
      analysis (TSA). RESULTS: Eleven studies met the inclusion criteria and were
      included in the review. Results of this systematic review revealed a small higher
      rate (2%) of early implant failure when a non-submerged healing approach is
      performed. Late implant failure appears not to be different in submerged or non
      submerged healing, but the power of evidence, as determined by TSA, is not high.
      If we consider MBL changes at 1 year from implant load, it seems that non
      submerged healing may better preserve marginal bone, although with a small effect
      size (0.13 mm). CONCLUSIONS: Implants placed with a non-submerged technique have
      a higher risk (2%) of early failure. The power of the evidence about the effects
      on MBL is low, but present results seem to favour non-submerged healing, although
      with a very small effect size.

PMID- 29574853
TI  - Prevalence and predictive factors of early postpartum diabetes among women with
      gestational diabetes in a single-center cohort.
AB  - OBJECTIVE: To determine the prevalence of diabetes at 6-12 weeks postpartum among
      women with gestational diabetes mellitus (GDM), and to identify prenatal
      postpartum diabetes predictors. METHODS: In the present prospective cohort study,
      glucose statuses of consecutive women newly diagnosed with hyperglycemia during
      pregnancy were evaluated at 6-12 weeks postpartum between November 1, 2015, and
      November 1, 2016, at Tygerberg Hospital, Cape Town, South Africa. Women with
      known diabetes were excluded. RESULTS: There were 78 patients included; 36 (46%)
      patients had abnormal postpartum glucose values (21 [27%] diabetes; 15 [19%] pre
      diabetes) and 29 (37%) had overt diabetes in pregnancy. In univariate analyses,
      GDM diagnosis before 24 weeks of pregnancy (P<0.001), degree of hyperglycemia at
      diagnosis (P=0.001), need for insulin (P=0.001), glycosylated hemoglobin (HbA1c)
      in the month preceding delivery (P=0.006), older than 36 years (P=0.039), family
      history of diabetes (P=0.048), and preterm labor (P=0.039) were risk factors for
      postpartum diabetes. Multivariate analyses confirmed family history of diabetes
      (OR 7.45, 95% CI 1.05-52.76; P=0.044), HbA1c at diagnosis (OR 5.33, 95% CI 2.25
      12.60; P<0.001), and age (OR 8.8, 95% CI 1.35-58.45; P=0.023), as robust
      predictors of diabetes after GDM. CONCLUSION: The high prevalence of diabetes
      supports early postpartum oral glucose tolerance testing. Several women had
      undiagnosed diabetes. The risk factors identified could be useful for prenatal
      risk stratification.

PMID- 29574854
TI  - Rheological characterization of thickened protein-based beverages under different
      food thickeners and setting times.
AB  - : The effects of different setting times (15-120 min) on the rheological
      properties of cold thickened protein-based beverage (PBB) samples prepared with
      different xanthan gum (XG)-based food thickeners were examined. In this study,
      four commercial XG-based food thickeners (coded A-D) and three commercial PBB
      products (whole milk, skim milk, and soybean milk) were used to prepare thickened
      PBB samples at a 3% thickener concentration. The fastest increases in etaa,50
      values of thickened PBB samples were observed at 15 min, and at longer time
      periods their etaa,50 values gradually increased or remained constant with an
      increase in setting time (15-120 min). The magnitudes of the rheological
      parameters (etaa,50 , K, G', and G") of thickened PBB samples with thickener A
      were significantly higher compared with those with other thickeners (coded B, C,
      and D). The flow and dynamic rheological properties of thickened PBB samples
      prepared with different XG-based thickeners were significantly different (p <
      .05), demonstrating that their rheological properties were greatly affected by
      the type of PBB and thickener as well as the setting time. PRACTICAL STATEMENTS:
      Food thickeners have been commonly used in the preparation of various thickened
      fluids with desirable rheological properties for dysphagic patients to elicit an
      optimal swallow response. However, among various thickened fluids, there is
      limited rheological information on cold thickened protein-based beverage (PBB)
      (e.g., whole milk, skim milk, and soybean milk) prepared with various xanthan gum
      (XG)-based thickeners. Our flow and dynamic rheological results showed that the
      flow and viscoelastic properties of the thickened PBB samples prepared with
      different food thickeners were dependent on the PBB type, thickener type, and
      setting time. These rheological results presented in this study will provide both
      thickener manufacturers and clinicians with valuable information for thickened
      PBB products with desirable rheological properties for safe and easy swallowing.
      New knowledge of the different rheological characterizations of thickened PBB can
      be practically applied to develop the commercial dysphagia thickeners suitable
      for PBB in food industry.

PMID- 29574855
TI  - Pathotyping of Escherichia coli isolated from community toilet wastewater and
      stored drinking water in a slum in Bangladesh.
AB  - : This study investigated the occurrence of Escherichia coli pathotypes in
      sanitary wastewater and drinking water in a Bangladeshi urban slum and the
      potential associations between these sources. We examined 621 E. coli isolates
      from sanitary wastewater and stored drinking water by multiplex PCR and dual
      index sequencing, classifying them into eight pathotypes based on 14 virulence
      genes and additionally evaluating the possession of the human-specific E. coli
      genetic biomarker H8. The proportions of pathogenic E. coli were significantly
      different (P < 0.001) between wastewater (18.6%) and drinking water (1.7%). StIb
      positive enterotoxigenic E. coli (ETEC) were predominant in wastewater,
      indicating that people in the site carried ETEC. In contrast, no ETEC was present
      in drinking water and the proportion of H8-positive isolates was significantly
      smaller (7.8%) than that in wastewater (16.3%) (P = 0.001). Our findings indicate
      that sanitary wastewater from the slum was heavily contaminated with pathogenic
      E. coli, posing a great health risk. Furthermore, E. coli contamination of
      drinking water could be derived from not only human but also other sources.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Sanitary wastewater from an urban slum was
      heavily contaminated with pathogenic Escherichia coli. It is worth noting a great
      health risk of accidental exposure to pathogenically contaminated wastewater
      improperly discharged in and around urban slums. The distinct difference in
      pathotypes between wastewater and drinking water and the significantly smaller
      positive proportion of the human-specific E. coli genetic biomarker (H8) in
      drinking water indicate that drinking water contamination could be derived from
      not only human but also other sources. This highlights that pathotyping in
      association with the H8 marker provides an indication of pathogen contamination
      sources of environmental transmission media.

PMID- 29574856
TI  - HU deviation in lung and bone tissues: Characterization and a corrective
      strategy.
AB  - INTRODUCTION: In the era of precision medicine, quantitative applications of x
      ray Computed Tomography (CT) are on the rise. These require accurate measurement
      of the CT number, also known as the Hounsfield Unit. In this study, we evaluated
      the effect of patient attenuation-induced beam hardening of the x-ray spectrum on
      the accuracy of the HU values and a strategy to correct for the resulting
      deviations in the measured HU values. MATERIALS AND METHODS: A CIRS electron
      density phantom was scanned on a Siemens Biograph mCT Flow CT scanner and a GE
      Discovery 710 CT scanner using standard techniques that are employed in the
      clinic to assess the HU deviation caused by beam hardening in different tissue
      types. In addition, an anthropomorphic ATOM adult male upper torso phantom was
      scanned on the GE Discovery 710 scanner. Various amounts of Superflab bolus
      material were wrapped around the phantoms to simulate different patient sizes.
      The mean HU values that were measured in the phantoms were evaluated as a
      function of the water-equivalent area (Aw ), a parameter that is described in the
      report of AAPM Task Group 220. A strategy by which to correct the HU values was
      developed and tested. The variation in the HU values in the anthropomorphic ATOM
      phantom under different simulated body sizes, both before and after correction,
      were compared, with a focus on the lung and bone tissues. RESULTS: Significant HU
      deviations that depended on the simulated patient size were observed. A positive
      correlation between HU and Aw was observed for tissue types that have an HU of
      less than zero, while a negative correlation was observed for tissue types with
      HU values that are greater than zero. The magnitude of the difference increases
      as the underlying attenuation property deviates further away from that of water.
      In the electron density phantom study, the maximum observed HU differences
      between the measured and reference values in the cortical bone and lung materials
      were 426 and 94 HU, respectively. In the anthropomorphic phantom study, the HU
      difference was as much as -136.7 +/- 8.2 HU (or -7.6% +/- 0.5% of the attenuation
      coefficient, AC) in the spine region, and up to 37.6 +/- 1.6 HU (or 17.3% +/-
      0.8% of AC) in the lung region between scenarios that simulated normal and obese
      patients. Our HU correction method reduced the HU deviations to 8.5 +/- 9.1 HU
      (or 0.5% +/- 0.5%) for bone and to -6.4 +/- 1.7 HU (or -3.0% +/- 0.8%) for lung.
      The HU differences in the soft tissue materials before and after the correction
      were insignificant. Visual improvement of the tissue contrast was also achieved
      in the data of the simulated obese patient. CONCLUSIONS: The effect of a
      patient's size on the HU values of lung and bone tissues can be significant. The
      accuracy of those HU values was substantially improved by the correction method
      that was developed for and employed in this study.

PMID- 29574857
TI  - Accuracy of Medical Students in Detecting Pleural Effusion Using Lung Ultrasound
      as an Adjunct to the Physical Examination.
AB  - OBJECTIVES: This study compared the accuracy of medical students in identifying
      pleural effusion in hospitalized patients using the physical examination versus
      lung ultrasound (US). METHODS: Fourth-year medical students (n = 14) received 20
      hours of general practical US training (including 2 hours of specialized lung US
      training) plus theoretical and video documentation. The students used the
      physical examination alone versus the physical examination plus lung US to
      document the presence or absence of pleural effusion in the right and left
      hemithoraces of hospitalized patients (n = 11 patients; 22 hemithoraces examined
      544 times in total). The reference standard for identification of pleural
      effusion was a lung US examination by 2 expert point-of-care sonographers.
      RESULTS: The odds of correctly identifying the presence versus absence of pleural
      effusion was 5 times greater with lung US as an adjunct to the physical
      examination compared to the physical examination alone (odds ratio [OR], 5.1 from
      multivariate logistic regression; 95% confidence interval, 3.3-8.0). The addition
      of lung US to the physical examination resulted in an increase in sensitivity
      from 48% to 90%, in specificity from 73% to 86%, and in accuracy from 60% to 88%.
      The benefits of using US were greater when pleural effusion was present versus
      absent (OR, 10.8 versus 2.4) and when examining older versus younger patients
      (OR, 10.2 versus 2.8). CONCLUSIONS: These results demonstrate that medical
      students' ability to detect the presence or absence of pleural effusion is
      superior when using lung US as an adjunct to the physical examination than when
      using the physical examination alone.

PMID- 29574858
TI  - Acute deep vein thrombosis suppresses peripheral T cell effector function.

PMID- 29574859
TI  - Potential improvements of lung and prostate MLC tracking investigated by
      treatment simulations.
AB  - PURPOSE/OBJECTIVES: Intrafraction tumor motion during external radiotherapy is a
      challenge for the treatment accuracy. A novel technique to mitigate the impact of
      tumor motion is real-time adaptation of the multileaf collimator (MLC) aperture
      to the motion, also known as MLC tracking. Although MLC tracking improves the
      dosimetric accuracy, there are still residual errors. Here, we investigate and
      rank the performance of five prediction algorithms and seven improvements of an
      MLC tracking system by extensive tracking treatment simulations. MATERIALS AND
      METHODS: An in-house-developed MLC tracking simulator that has been
      experimentally validated against an electromagnetic-guided MLC tracking system
      was used to test the prediction algorithms and tracking system improvements. The
      simulator requires a Dicom treatment plan and a motion trajectory as input and
      outputs all motion of the accelerator during MLC tracking treatment delivery. For
      lung tumors, MLC tracking treatments were simulated with a low and a high
      modulation VMAT plan using 99 patient-measured lung tumor trajectories. For
      prostate, tracking was also simulated with a low and a high modulation VMAT plan,
      but with 695 prostate trajectories. For each simulated treatment, the tracking
      error was quantified as the mean MLC exposure error, which is the sum of the
      overexposed area (irradiated area that should have been shielded according to the
      treatment plan) and the underexposed area (shielded area that should have been
      irradiated). First, MLC tracking was simulated with the current MLC tracking
      system without prediction, with perfect prediction (Perfect), and with the
      following five prediction algorithms: linear Kalman filter (Kalman), kernel
      density estimation (KDE), linear adaptive filtering (LAF), wavelet-based
      multiscale autoregression (wLMS), and time variant seasonal autoregression
      (TVSAR). Next, MLC tracking was simulated using the best prediction algorithm and
      seven different tracking system improvements: no localization signal latency (a),
      doubled maximum MLC leaf speed (b), halved MLC leaf width (c), use of Y backup
      jaws to track motion perpendicular to the MLC leaves (d), dynamic collimator
      rotation for alignment of the MLC leaves with the dominant target motion
      direction (e), improvements 4 and 5 combined (f), and all improvements combined
      (g). RESULTS: All results are presented as the mean residual MLC exposure error
      compared to no tracking. In the prediction study, the residual MLC exposure error
      was 47.0% (no prediction), 45.1% (Kalman), 43.8% (KDE), 43.7% (LAF), 42.1%
      (wLMS), 40.1% (TVSAR), and 36.5% (Perfect) for lung MLC tracking. For prostate
      MLC tracking, it was 66.0% (no prediction), 66.9% (Kalman), and 63.4% (Perfect).
      For lung with TVSAR prediction, the residual MLC exposure error for the seven
      tracking system improvements was 37.2%(1), 38.3%(2), 37.4%(3), 34.2%(4),
      30.6%(5), 27.7%(6), and 20.7%(7). For prostate with no prediction, the residual
      MLC exposure error was 61.7%(1), 61.4%(2), 55.4%(3), 57.2%(4), 47.5%(5),
      43.7%(6), and 38.7%(7). CONCLUSION: For prostate, MLC tracking was slightly
      better without prediction than with linear Kalman filter prediction. For lung,
      the TVSAR prediction algorithm performed best. Dynamic alignment of the
      collimator with the dominant motion axis was the most efficient MLC tracking
      improvement except for lung tracking with the low modulation VMAT plan, where jaw
      tracking was slightly better.

PMID- 29574860
TI  - A dietary pattern based on estrogen metabolism is associated with breast cancer
      risk in a prospective cohort of postmenopausal women.
AB  - Increased exposure to estrogen is a risk factor for postmenopausal breast cancer,
      and dietary factors can influence estrogen metabolism. However, studies of diet
      and breast cancer have been inconclusive. We developed a dietary pattern
      associated with levels of unconjugated estradiol and the ratio of 2- and 16
      hydroxylated estrogen metabolites in a subsample of Prostate, Lung, Colorectal
      and Ovarian Screening Trial (PLCO) participants (n = 653) using reduced rank
      regression, and examined its association with postmenopausal breast cancer
      prospectively in the larger PLCO cohort (n = 27,488). The estrogen-related
      dietary pattern (ERDP) was comprised of foods with positively-weighted intakes
      (non-whole/refined grains, tomatoes, cruciferous vegetables, cheese,
      fish/shellfish high in omega-3 fatty acids, franks/luncheon meats) and negatively
      weighted intakes (nuts/seeds, other vegetables, fish/shellfish low in omega-3
      fatty acids, yogurt, coffee). A 1-unit increase in the ERDP score was associated
      with an increase in total (HR: 1.09, 95% CI: 1.01-1.18), invasive (HR: 1.13; 95%
      CI: 1.04-1.24) and estrogen receptor (ER)-positive (HR: 1.13, 95% CI: 1.02-1.24)
      breast cancer risk after adjustment for confounders. Associations were observed
      for the fourth quartile of ERDP compared with the first quartile for overall
      breast cancer (HR: 1.14; 95% CI: 0.98-1.32), invasive cases (HR: 1.20, 95% CI:
      1.02-1.42) and ER-positive cases (HR: 1.19; 95% CI: 0.99-1.41). The increased
      risk associated with increasing ERDP score was more apparent in strata of some
      effect modifiers (postmenopausal hormone therapy non-users and non-obese
      participants) where the relative estrogen exposure due to that factor was lowest,
      although the p values for interaction were not statistically significant. Results
      suggest a dietary pattern based on estrogen metabolism is positively associated
      with postmenopausal breast cancer risk, possibly through an estrogenic influence.

PMID- 29574861
TI  - Updated Retrospective Single-Center Comparative Analysis of Peripheral Nerve
      Block Complications Using Landmark Peripheral Nerve Stimulation Versus Ultrasound
      Guidance as a Primary Means of Nerve Localization.
AB  - OBJECTIVES: The purpose of this study was to perform an updated analysis of
      complications associated with upper and lower extremity peripheral nerve blocks
      (PNBs) performed with ultrasound (US) guidance versus the landmark approach.
      METHODS: We conducted a single-center retrospective cohort analysis to compare
      the incidence of PNB complications between the techniques. The primary outcome
      was local anesthetic systemic toxicity (LAST), whereas the secondary outcomes
      included short- and long-term nerve injuries. The current query included cases
      performed between 2012 and 2015. A combined analysis included data extending to
      2006. The Statistical examination relied on the chi2 test. RESULTS: During this 4
      year period, we performed 7789 US-guided and 498 landmark-guided blocks with no
      statistically significant difference in the incidence of nerve injury or LAST
      between the groups. Our 10-year analysis, however, revealed a significant
      increase (P < .01) in the rate of LAST with the landmark technique: 7 of 5932
      versus 0 of 16,858 cases. The combined data also revealed a significant increase
      (P < .01) in short-term injuries associated with the landmark approach (30 of
      5932 versus 33 of 16,858) but no significant difference in the incidence of long
      term injuries. CONCLUSIONS: Our analysis supports a conclusion that the use of US
      guidance during PNBs leads to a significant reduction in the incidence of LAST,
      adding to growing evidence from similar investigations. The impact of US on the
      incidence of nerve injuries remains unclear, considering that the nature of
      transient deficits is thought to be multifactorial, and the frequency of lasting
      injuries did not differ significantly in this study.

PMID- 29574862
TI  - High amplitude and low frequency cyclic mechanical strain promotes degeneration
      of human nucleus pulposus cells via the NF-kappaB p65 pathway.
AB  - Disc degeneration alters the structure and function of intervertebral discs and
      is the basis of spinal degenerative diseases. To establish the molecular
      mechanism of intervertebral disc degeneration caused by mechanical strain, this
      study examined the effects of different amplitude (3%, 9%, 19%) cyclic mechanical
      strain (CMS) at a low frequency (0.01 Hz) on the secretion of cartilage
      extracellular matrix, expression of inflammatory cytokines and catabolic
      proteases, and activation of NF-kappaB signaling pathway in human nucleus
      pulposus cells. We also investigated effects of low frequency and high amplitude
      (19%) CMS on degeneration of human nucleus pulposus cells in the presence or
      absence of p65 inhibitor, p65 silencing shRNA, or p65 overexpression. While 3%
      CMS did not significantly decrease aggrecan or type II collagen expression, or
      increase TNF-alpha, IL-1beta, IL-6 expression, 9% and 19% CMS showed the
      significant effects. Low frequency and high amplitude (19%) CMS was found to
      promote p65 activation in human nucleus pulposus cells, and IL-1beta was found to
      promote p65 nuclear translocation though IkappaB kinase phosphorylation.
      Furthermore, degeneration process of nucleus pulposus cells was found attenuated
      in the presence of p65 inhibitor or p65 silencing shRNA, but promoted with p65
      overexpression. These data suggest that high amplitude and low frequency CMS
      could promote degeneration of human nucleus pulposus cells significantly via the
      NF-kappaB p65 pathway. Our findings have uncovered the effect of CMS on human
      nucleus pulposus cell degeneration and have identified a previously unknown
      intrinsic underlying mechanism.

PMID- 29574864
TI  - Erratum for Peng, Zhou, Xie, et al. (2017) DOI: 10.1002/pd.5169.

PMID- 29574863
TI  - Deciphering the molecular mechanism and apoptosis underlying the in-vitro and in
      vivo chemotherapeutic efficacy of vanadium luteolin complex in colon cancer.
AB  - : The present study is carried out to reveal the chemotherapeutic effects of
      vanadium luteolin complex against HT-29 human colon carcinoma cell line and
      chemically induced rat colon carcinoma. Our investigation revealed that the
      vanadium luteolin complex induces apoptosis in HT-29 cells in a dose-dependent
      manner. Furthermore, the study also confirmed that the vanadium luteolin complex
      increased caspase-3 and p53 expression whereas reduced the VEGF, mTOR, Akt
      expression, and induced DNA fragmentation in HT-29 cells. The oral acute and sub
      acute toxicity and the DNA binding efficacy of the complex with CT-DNA were
      investigated. The vanadium luteolin complex showed mortality at a dose of 120
      mg/kg dose. The sub-acute toxicity of the complex at the dose of 90 mg/kg
      presented an increased level of WBC count, total bilirubin, ALT, AST, ALP,
      creatinine, blood urea nitrogen, and decreased level of total protein compared
      with the control group. Histopathological alterations in kidney, liver, stomach,
      and lungs was observed at a dose of 90 mg/kg of the complex. The dose of 45 mg/kg
      of the complex was found to have better chemotherapeutic activity by
      significantly reducing the incidences of aberrant crypt foci formation,
      upregulation in the expression of p53 and Bax, and downregulation of the
      expression of Bcl2, and cell proliferation was found in the complex at a dose of
      45 mg/kg. Our findings from the study support that the complex possesses a
      potential chemotherapeutic activity against colon cancer and was efficient in
      reducing aberrant crypt foci formation multiplicity, hyperplastic lesions in the
      colon tissues of rats by inducing apoptosis. SIGNIFICANCE: The present study
      demonstrates that the effect of vanadium-luteolin complex in HT-29 cells and
      dimethylhydrazine challenged rats, curtail cell proliferation through induction
      of apoptosis mediated via activation of the key proteins involved in the
      intrinsic pathway like p53, Bax, caspase-3 and downregulating Bcl2, mTOR/Akt,
      angiogenic factor VEGF along with aberrant crypt foci formation multiplicity, and
      PCNA in the colon mucosa. Our combinatorial approach shows higher efficacy at
      considerably lower doses minimizing side effects. Insights into in-vitro and in
      vivo results provide strong proof that low dose chemotherapeutic regimens can
      suppress, reverse, or delay the progression of colon cancer by modulating
      intrinsic apoptotic as well as antiangiogenic pathways.

PMID- 29574866
TI  - Surgical treatment of peri-implantitis using enamel matrix derivative, an RCT: 3-
      and 5-year follow-up.
AB  - OBJECTIVE: To assess the clinical and radiographic outcomes 3 and 5 years after
      the surgical treatment of peri-implantitis per se or in combination with an
      enamel matrix derivative (EMD). MATERIALS AND METHODS: At baseline, 29 patients
      were randomized to surgical treatment with adjunctive EMD or no EMD. One year
      after the surgical treatment of peri-implantitis, 25 patients remained eligible
      for survival analyses at the 3- and 5-year follow-up. The primary outcomes were
      implant loss and bone level (BL) change measured on radiographs, and the
      secondary outcomes, bleeding on probing, pus and plaque at each implant were
      analysed in 18 and 14 patients at the 3- and 5-year follow-up, respectively.
      RESULTS: After exclusion of four patients who discontinued the study, at the 3
      year follow-up, 13 (100%) implants survived in the EMD group, and 10 of 12 (83%)
      in the non-EMD group. At the 5-year follow-up, 11 of 13 (85%) implants in the EMD
      group and nine of 12 (75%) in the non-EMD group survived. In multivariate
      modelling, BL changes and EMD treatment were positively associated with implant
      survival. Similarly, the same trend was seen in univariate analysis. CONCLUSIONS:
      An exploratory analysis suggests that adjunctive EMD is positively associated
      with implant survival up to 5 years, but larger studies are needed.

PMID- 29574865
TI  - Rheumatologic complications in a cohort of 227 patients with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is the most prevalent symptomatic type of
      human primary immunodeficiency diseases (PID). Clinically, CVID is characterized
      by increased susceptibility to infections and a wide variety of autoimmune and
      rheumatologic disorders. All patients with CVID registered in Iranian PID
      Registry (IPIDR) were enrolled in this retrospective cohort study. We
      investigated the frequency of rheumatologic diseases and its association with
      immunological and clinical phenotypes in patients with CVID. A total of 227
      patients with CVID were enrolled in this study. The prevalence of rheumatologic
      disorders was 10.1% with a higher frequency in women than men. Most common
      rheumatologic manifestations were juvenile idiopathic arthritis (JIA) and adult
      rheumatoid arthritis (RA) followed by juvenile spondyloarthritis (JSpA) and
      undifferentiated inflammatory arthritis (UIA). Septic arthritis in patients with
      CVID with a history of RA and JIA was higher than patients without rheumatologic
      complication. Patients with CVID with a history of autoimmunity (both
      rheumatologic and non-rheumatologic autoimmunity) had lower regulatory T cells
      counts in comparison with patients without autoimmune disorders. There was an
      association between defect in specific antibody responses and negative serologic
      test results in patients with rheumatologic manifestations. JIA, RA, JSpA and UIA
      are the most frequent rheumatologic disorders in patients with CVID. Due to
      antibody deficiency, serologic tests may be negative in these patients.
      Therefore, these conditions pose significant diagnostic and therapeutic
      challenges for immunologists and rheumatologists in charge of the care for these
      patients.

PMID- 29574868
TI  - Corrigendum.

PMID- 29574867
TI  - Editorial: is proton pump inhibitor use associated with worse outcomes in
      patients with liver abscesses? Authors' reply.

PMID- 29574869
TI  - Letter: the role of direct-acting anti-virals in determining the risk of
      hepatocellular carcinoma development in patients with hepatitis C virus-induced
      cirrhosis.

PMID- 29574870
TI  - Editorial: diabetes, obesity and clinical inertia-the recipe for advanced NASH.

PMID- 29574871
TI  - Letter: the role of direct-acting anti-virals in determining the risk of
      hepatocellular carcinoma development in patients with hepatitis C virus-induced
      cirrhosis-Authors' reply.

PMID- 29574872
TI  - Editorial: use of beta-blockers and of band ligation in preventing first and
      recurrent variceal bleeding-"real life" vs evidence-based decisions.

PMID- 29574873
TI  - Editorial: is proton pump inhibitor use associated with worse outcomes in
      patients with liver abscesses?

PMID- 29574874
TI  - Editorial: use of beta-blockers and band ligation in preventing first and
      recurrent variceal bleeding-"real life" vs evidence-based decisions. Authors'
      reply.

PMID- 29574875
TI  - Editorial: diabetes, obesity and clinical inertia-the recipe for advanced NASH.
      Authors' reply.

PMID- 29574876
TI  - Editorial: first among Equals-not for either infliximab or adalimumab in Crohn's
      disease-yet.

PMID- 29574877
TI  - Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan
      resistant colorectal cancer cells in vitro and in vivo.
AB  - Irinotecan (CPT11) and Oxaliplatin have been used in combination with
      fluorouracil and leucovorin for treating colorectal cancer. However, the efficacy
      of these drugs is reduced due to various side effects and drug resistance.
      Fisetin, a hydroxyflavone possess anti-proliferative, anti-cancer, anti
      inflammatory, and antioxidant activity against various types of cancers. Apart
      from that, fisetin has been shown to induce cytotoxic effects when combined with
      other known chemotherapeutic drugs. In this study, we aimed to investigate
      whether Fisetin was capable of sensitizing both Irinotecan and Oxaliplatin
      resistance colon cancer cells and explored the possible signaling pathways
      involved using In vitro and In vivo models. The results showed that Fisetin
      treatment effectively inhibited cell viability and apoptosis of CPT11-LoVo cells
      than Oxaliplatin (OR) and parental LoVo cancer cells. Western blot assays
      suggested that apoptosis was induced by fisetin administration, promoting Caspase
      8, and Cytochrome-C expressions possibly by inhibiting aberrant activation of
      IGF1R and AKT proteins. Furthermore, fisetin inhibited tumor growth in athymic
      nude mouse xenograft model. Overall, our results provided a basis for Fisetin as
      a promising agent to treat parental as well as chemoresistance colon cancer.

PMID- 29574878
TI  - Effect of Emergency Physician-Performed Point-of-Care Ultrasound and Radiology
      Department-Performed Ultrasound Examinations on the Emergency Department Length
      of Stay Among Pregnant Women at Less Than 20 Weeks' Gestation.
AB  - OBJECTIVES: We sought to confirm retrospective studies that measured an
      approximately 20% reduction in emergency department (ED) length of stay (LOS) in
      early-gestation pregnant women who receive emergency physician-performed point-of
      care ultrasound (US) examinations rather than radiology department-performed US
      examinations for evaluation of intrauterine pregnancy (IUP). METHODS: A
      randomized controlled clinical trial was performed at an urban academic safety
      net hospital and 2 Naval medical centers in the United States. The allocation was
      concealed before enrollment. Clinically stable adult pregnant women at less than
      20 weeks' gestation who presented to the ED with abdominal pain or vaginal
      bleeding were randomized to receive a point-of-care or radiology US to assess for
      IUP. The primary outcome measure was the ED LOS. RESULTS: A total of 224 patients
      (point-of-care US, n = 118; radiology US, n = 106) were included for the
      analysis. The ED LOS was 20 minutes shorter in the point-of-care US arm (95%
      confidence interval [CI], -54 to 7 minutes). Adjusting for variability due to the
      location, the ED LOS was calculated to be 31 minutes shorter (95% CI, -64 to 1
      minute) than for patients in the radiology US arm. Excluding patients in the
      point-of-care US arm who crossed over to radiology US after an inconclusive point
      of-care US examination, the ED LOS was 75 minutes shorter than in the radiology
      US arm (95% CI, -97 to -53 minutes). CONCLUSIONS: Early-gestation pregnant ED
      patients requiring pelvic US were discharged earlier when point-of-care US was
      used rather than radiology US; however, this trial did not achieve our target of
      30 minutes. Nevertheless, our data support the routine use of ED point-of-care US
      for IUP, saving the most time if a conclusive IUP is identified.

PMID- 29574879
TI  - Class C ARFs evolved before the origin of land plants and antagonize
      differentiation and developmental transitions in Marchantia polymorpha.
AB  - A plethora of developmental and physiological processes in land plants is
      influenced by auxin, to a large extent via alterations in gene expression by
      AUXIN RESPONSE FACTORs (ARFs). The canonical auxin transcriptional response
      system is a land plant innovation, however, charophycean algae possess
      orthologues of at least some classes of ARF and AUXIN/INDOLE-3-ACETIC ACID
      (AUX/IAA) genes, suggesting that elements of the canonical land plant system
      existed in an ancestral alga. We reconstructed the phylogenetic relationships
      between streptophyte ARF and AUX/IAA genes and functionally characterized the
      solitary class C ARF, MpARF3, in Marchantia polymorpha. Phylogenetic analyses
      indicate that multiple ARF classes, including class C ARFs, existed in an
      ancestral alga. Loss- and gain-of-function MpARF3 alleles result in pleiotropic
      effects in the gametophyte, with MpARF3 inhibiting differentiation and
      developmental transitions in multiple stages of the life cycle. Although loss-of
      function Mparf3 and Mpmir160 alleles respond to exogenous auxin treatments,
      strong miR-resistant MpARF3 alleles are auxin-insensitive, suggesting that class
      C ARFs act in a context-dependent fashion. We conclude that two modules
      independently evolved to regulate a pre-existing ARF transcriptional network.
      Whereas the auxin-TIR1-AUX/IAA pathway evolved to repress class A/B ARF activity,
      miR160 evolved to repress class C ARFs in a dynamic fashion.

PMID- 29574880
TI  - Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron
      functions in a temporal lobe epilepsy model.
AB  - BACKGROUND AND PURPOSE: A non-psychoactive phytocannabinoid, cannabidiol (CBD),
      shows promising results as an effective potential antiepileptic drug in some
      forms of refractory epilepsy. To elucidate the mechanisms by which CBD exerts its
      anti-seizure effects, we investigated its effects at synaptic connections and on
      the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two
      major inhibitory interneurons: fast spiking, parvalbumin (PV)-expressing and
      adapting, cholecystokinin (CCK)-expressing interneurons. We also investigated
      whether in vivo treatment with CBD altered the fate of CCK and PV interneurons
      using immunohistochemistry. EXPERIMENTAL APPROACH: Electrophysiological
      intracellular whole-cell recordings combined with neuroanatomy were performed in
      acute brain slices of rat temporal lobe epilepsy in in vivo (induced by kainic
      acid) and in vitro (induced by Mg2+ -free solution) epileptic seizure models. For
      immunohistochemistry experiments, CBD was administered in vivo (100 mg.kg-1 ) at
      zero time and 90 min post status epilepticus, induced with kainic acid. KEY
      RESULTS: Bath application of CBD (10 MUM) dampened excitability at unitary
      synapses between pyramidal cells but enhanced inhibitory synaptic potentials
      elicited by fast spiking and adapting interneurons at postsynaptic pyramidal
      cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK and
      pyramidal cells in a cell type-specific manner. These neuroprotective effects of
      CBD were corroborated by immunohistochemistry experiments that revealed a
      significant reduction in atrophy and death of PV- and CCK-expressing interneurons
      after CBD treatment. CONCLUSIONS AND IMPLICATIONS: Our data suggest that CBD
      restores excitability and morphological impairments in epileptic models to pre
      epilepsy control levels through multiple mechanisms to reinstate normal network
      function.

PMID- 29574881
TI  - Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic
      change: a newly described variant.
AB  - AIMS: Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant
      tumour of the salivary glands. Because of its rarity, the histological variants
      of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases
      with prominent oncocytic change in the major salivary glands. METHODS AND
      RESULTS: We examined five cases, three males and two females (mean age = 63
      years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the
      parotid and submandibular glands. The lesions were macroscopically unilocular or
      multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour
      cell nests were also observed. As with classic LG-IDC, the cyst wall was
      surrounded by myoepithelial cells with no invasive component. The tumour cells
      had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or
      cribriform pattern. Immunohistochemically, the tumour cells were diffusely
      positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody,
      and were negative for androgen receptor and gross cystic disease fluid protein
      15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of
      myoepithelial cells in the intraductal tumour. CONCLUSION: Oncocytic LG-IDC
      should be recognised as a histologically unique variant of LG-IDC. Awareness of
      this entity is important to avoid erroneous diagnosis and inappropriate treatment
      for histological mimics.

PMID- 29574882
TI  - Prevalence and risk factors for myopia and other refractive errors in an adult
      population in southern India.
AB  - PURPOSE: To investigate prevalence and risk factors for myopia, hyperopia and
      astigmatism in southern India. METHODS: Randomly sampled villages were enumerated
      to identify people aged >=40 years. Participants were interviewed for
      socioeconomic and lifestyle factors and attended a hospital-based ophthalmic
      examination including visual acuity measurement and objective and subjective
      measurement of refractive status. Myopia was defined as spherical equivalent (SE)
      worse than -0.75 dioptres (D), hyperopia as SE >=+1D and astigmatism as cylinder
      <-0.5. RESULTS: The age-standardised prevalences of myopia, hyperopia and
      astigmatism were 35.6% (95% CI: 34.7-36.6), 17.0% (95% CI: 16.3-17.8) and 32.6
      (29.3-36.1), respectively. Of those with myopia (n = 1490), 70% had advanced
      cataract. Of these, 79% had presenting visual acuity (VA) less than 6/18 and
      after best correction, 44% of these improved to 6/12 or better and 27% remained
      with VA less than 6/18. In multivariable analyses (excluding patients with
      advanced cataract), increasing nuclear opacity score, current tobacco use, and
      increasing height were associated with higher odds of myopia. Higher levels of
      education were associated with increased odds of myopia in younger people and
      decreased odds in older people. Increasing time outdoors was associated with
      myopia only in older people. Increasing age and female gender were associated
      with hyperopia, and nuclear opacity score, increasing time outdoors, rural
      residence and current tobacco use with lower odds of hyperopia. After controlling
      for myopia, factors associated with higher odds of astigmatism were age, rural
      residence, and increasing nuclear opacity score and increasing education with
      lower odds. CONCLUSIONS: In contrast to high-income settings and in agreement
      with studies from low-income settings, we found a rise in myopia with increasing
      age reflecting the high prevalence of advanced cataract.

PMID- 29574883
TI  - Physiological stress response patterns during a blood donation.
AB  - BACKGROUND: Donating blood is associated with increased psychological stress.
      This study investigates whether a blood donation induces physiological stress and
      if response patterns differ by gender, donation experience and non-acute stress.
      STUDY DESIGN AND METHODS: In 372 donors, physiological stress [blood pressure,
      pulse rate, pulse rate variability (PRV)] was measured at seven moments during
      routine donation. PRV was assessed using time domain [root mean square of
      successive differences (RMSSD)] and frequency domain [high frequency (HF) and low
      frequency (LF) power] parameters. Non-acute stress was assessed by questionnaire.
      Shape and significance of time course patterns were assessed by fitting
      multilevel models for each stress measure and comparing men and women, first-time
      and experienced donors, and donors with high and low levels of non-acute stress.
      RESULTS: Significant response patterns were found for all stress measures, where
      levels of systolic blood pressure (F(1,1315) = 24.2, P < 0.001), RMSSD (F(1,1315)
      = 24.2, P < 0.001), LF (F(1,1627) = 14.1, P < 0.001) and HF (F(1,1624) = 34.0, P
      < 0.001) increased towards needle insertion and then decreased to values lower
      than when arriving at the donation centre. Diastolic blood pressure (F(1,1326) =
      50.9, P < 0.001) increased and pulse rate (F(1,1393) = 507.4, P < 0.001) showed a
      U-shaped curve. Significant group effects were found, that is, higher systolic
      blood pressure/pulse rate in women; higher pulse rate in first-time donors;
      higher RMSSD at arrival and from screening until leaving in first-time donors;
      and higher LF and HF in first-time donors. CONCLUSION: This study shows an
      increase in physiological stress related to needle insertion, followed by a
      decrease when leaving the donation centre. Some group effects were also found.

PMID- 29574884
TI  - Progress in the genetics of autism spectrum disorder.
AB  - : A genetic basis for autism spectrum disorder (ASD) is now well established, and
      with the availability of high-throughput microarray and sequencing platforms,
      major advances have been made in our understanding of genetic risk factors. Rare,
      often de novo, copy number and single nucleotide variants are both implicated,
      with many ASD-implicated genes showing pleiotropy and variable penetrance.
      Additionally, common variants are also known to play a role in ASD's genetic
      etiology. These new insights into the architecture of ASD's genetic etiology
      offer opportunities for the identification of molecular targets for novel
      interventions, and provide new insight for families seeking genetic counselling.
      WHAT THE PAPER ADDS: A number of rare genetic variants are implicated in autism
      spectrum disorder (ASD), with some showing recurrence. Common genetic variants
      are also important and a number of loci are now being uncovered. Genetic testing
      for individuals with ASD offers the opportunity to identify relevant genetic
      etiology.

PMID- 29574885
TI  - Cholinergic innervation of principal neurons in the cochlear nucleus of the
      Mongolian gerbil.
AB  - Principal neurons in the ventral cochlear nucleus (VCN) receive powerful
      ascending excitation and pass on the auditory information with exquisite temporal
      fidelity. Despite being dominated by ascending inputs, the VCN also receives
      descending cholinergic connections from olivocochlear neurons and from higher
      regions in the pontomesencephalic tegmentum. In Mongolian gerbils, acetylcholine
      acts as an excitatory and modulatory neurotransmitter on VCN neurons, but the
      anatomical structure of cholinergic innervation of gerbil VCN is not well
      described. We applied fluorescent immunohistochemical staining to elucidate the
      development and the cellular localization of presynaptic and postsynaptic
      components of the cholinergic system in the VCN of the Mongolian gerbil. We found
      that cholinergic fibers (stained with antibodies against the vesicular
      acetylcholine transporter) were present before hearing onset at P5, but
      innervation density increased in animals after P10. Early in development
      cholinergic fibers invaded the VCN from the medial side, spread along the
      perimeter and finally innervated all parts of the nucleus only after the onset of
      hearing. Cholinergic fibers ran in a rostro-caudal direction within the nucleus
      and formed en-passant swellings in the neuropil between principal neurons.
      Nicotinic and muscarinic receptors were expressed differentially in the VCN, with
      nicotinic receptors being mostly expressed in dendritic areas while muscarinic
      receptors were located predominantly in somatic membranes. These anatomical data
      support physiological indications that cholinergic innervation plays a role in
      modulating information processing in the cochlear nucleus.

PMID- 29574886
TI  - Patient characteristics associated with peglyated interferon alfa-2a induced
      neutropenia in chronic hepatitis C patients.
AB  - Neutropenia is a haematologic disorder commonly reported in patients with chronic
      hepatitis C virus (HCV) infection treated with pegylated interferon alfa-2a (PEG
      IFN alpha-2a). The objective of the present project is to identify patient
      characteristics associated with neutropenia in hepatitis C patients. Demographic,
      clinical, and genetic data from 715 patients with chronic HCV infection treated
      with PEG-IFN alpha-2a and ribavirin. The outcome variable was the development of
      grade 3 or 4 neutropenia, defined as the decrease in neutrophil counts below 1
      109 /L anytime during study. Predictors of neutropenia were identified using a 2
      stage approach. First, univariate analysis was performed to identify possible
      predictors of neutropenia. T test was used for continuous variables and Fisher's
      exact test was used for categorical variables. Second, multiple logistic
      regression with stepwise addition was then performed using predictors identified
      in the univariate analysis step to produce final model containing independent
      predictors at P < .05. Logistic regression identified female gender, absolute
      neutrophils counts, and cholesterol level as the main predictors of neutropenia.
      Female gender increases the odds of experiencing neutropenia by 86% compared to
      male gender. A 1 unit (mmol/L) increase in cholesterol level decreases the odds
      of developing neutropenia by 13%. A 55% reduction in the likelihood of developing
      neutropenia for a 1 unit (109 /L) increase in the absolute neutrophils counts.
      Patients with high risk of developing neutropenia can be identified.
      Identification of this cohort allows early intervention to prevent neutropenia.
      Possible intervention is to administer drugs that raise neutrophil count such as
      filgrastim before neutropenia occurs.

PMID- 29574887
TI  - Is exercise stress echocardiography useful in patients with suspected obstructive
      coronary artery disease who have resting left bundle branch block?
AB  - BACKGROUND: Current guidelines support exercise stress echocardiography (ESE) for
      evaluation of suspected obstructive coronary artery disease (OCAD) in ambulant
      patients with left bundle branch block (LBBB). Data regarding the diagnostic
      utility of ESE in patients with LBBB are limited. HYPOTHESIS: We hypothesized
      that the diagnostic performance of ESE for the assessment of suspected OCAD is
      reduced in the context of LBBB. METHODS: We studied 191 consecutive patients with
      resting LBBB undergoing ESE for the investigation of suspected OCAD between 2008
      and 2015 at our center. The studies were categorized as inconclusive, normal, or
      abnormal. Patients with an abnormal response were subcategorized as regional
      ischemic response or globally abnormal. RESULTS: Eighty-two patients (43%)
      demonstrated a normal left ventricular contractile response (LVCR) to exercise;
      92 (48%) developed an abnormal LVCR to exercise, including 70 patients with
      globally abnormal and 22 patients with regional ischemic responses. Of the
      patients with abnormal responses, 62 patients had anatomic imaging, only 29 of
      whom had significant OCAD, conferring an overall specificity of ESE for
      significant OCAD of 21% and accuracy of 52%. Of patients who developed a
      regionally abnormal response, 89% had significant OCAD. CONCLUSIONS: For patients
      with LBBB who develop a globally abnormal LVCR during ESE, the specificity of ESE
      for reliably excluding significant OCAD is significantly reduced. ESE appears to
      be a suboptimal test for the evaluation of OCAD in patients with resting LBBB, as
      about 50% of patients will have an abnormal response, the majority due to
      globally abnormal contraction where OCAD cannot be reliably diagnosed.
      Alternative testing should be considered for the investigation of suspected OCAD
      in patients with resting LBBB.

PMID- 29574888
TI  - Corticosteroid therapy in pneumonia from swine-origin influenza A (H1N1) in
      China.
AB  - The first three cases of confirmed infection with the virus in China were
      documented between May 10 and May 15, 2009. Although the clinical characteristics
      of the H1N1 pneumonia were described in clinical reports, the therapy has few
      been described. Therefore, we report our experiences of 53 cases of the H1N1
      pneumonia with treatment. We describe clinical characteristic of 53 patients who
      were hospitalized for laboratory-confirmed H1N1 pneumonia at the 2nd Clinical
      College of Harbin Medical University. In addition, we measure the role of
      corticosteroid, mechanical ventilation, and non-corticosteroid antiviral therapy
      in the management of pneumonia patients with novel H1N1 infection. Real-time
      reverse-transcriptase-polymerase chain (RT-PCR) testing was used to confirm
      infection. The outcome of therapy was compared in scores of PaO2 and CT. The data
      was statistical analyzed by the Shapiro-Wilk, anova, Student-Newman-Keuls Test,
      and Kruskal-Wallis Test. The most common symptoms were dyspnea. In moderate ill
      patients, the changes in the increased PaO2 were lower in the non-corticosteroid
      antiviral therapy group than in the combination of corticosteroid and non
      corticosteroid antiviral therapy after 5 days' therapy. The therapy protocol of
      non-corticosteriod + mechanical ventilation played important role in the recovery
      of severe ill patients.

PMID- 29574889
TI  - System for image-guided resection of nonpalpable breast lesions: Proof of
      concept.
AB  - PURPOSE: In breast-conserving surgery (BCS), the cancer is sometimes incompletely
      excised, leading to reduced patient survival. To pursue complete excisions,
      radioactive seed localization (RSL) may be used to insert an iodine-125 seed into
      the tumor. The seed is used as a marker for the location of the tumor during
      surgery. RSL does not, however, show the extent of the tumor. Based on RSL, we
      pursue to visualize the seed location together with the extent from diagnostic
      images. METHODS: A system with two gamma-camera heads and two parallel-hole
      collimators was recently proposed to triangulate the location of an iodine-125
      seed during BCS. In the present study, this system was extended with a range
      camera to visualize a sphere centered on the seed in relation to the breast. This
      sphere contains the entire tumor and thus defines the target volume for BCS.
      Physical experiments with acrylic block phantoms (thickness ranging from 3.5 to
      6.5 cm) were performed to assess the absolute bias and the precision with which
      this sphere can be visualized. RESULTS: When a 6.5 cm thick phantom was used,
      along the horizontal plane, the target volume was visualized with an absolute
      bias and a precision of 2.1 and 0.8 mm, respectively. Along the vertical axis
      (i.e., z-axis), these values were 4.2 and 2.8 mm, respectively. CONCLUSIONS: The
      proposed system visualizes the target volume with an absolute bias that may be
      acceptable for BCS.

PMID- 29574890
TI  - Revision of Corallinaceae (Corallinales, Rhodophyta): recognizing Dawsoniolithon
      gen. nov., Parvicellularium gen. nov. and Chamberlainoideae subfam. nov.
      containing Chamberlainium gen. nov. and Pneophyllum.
AB  - A multi-gene (SSU, LSU, psbA, and COI) molecular phylogeny of the family
      Corallinaceae (excluding the subfamilies Lithophylloideae and Corallinoideae)
      showed a paraphyletic grouping of six monophyletic clades. Pneophyllum and
      Spongites were reassessed and recircumscribed using DNA sequence data integrated
      with morpho-anatomical comparisons of type material and recently collected
      specimens. We propose Chamberlainoideae subfam. nov., including the type genus
      Chamberlainium gen. nov., with C. tumidum comb. nov. as the generitype, and
      Pneophyllum. Chamberlainium is established to include several taxa previously
      ascribed to Spongites, the generitype of which currently resides in
      Neogoniolithoideae. Additionally we propose two new genera, Dawsoniolithon gen.
      nov. (Metagoniolithoideae), with D. conicum comb. nov. as the generitype and
      Parvicellularium gen. nov. (subfamily incertae sedis), with P. leonardi sp. nov.
      as the generitype. Chamberlainoideae has no diagnostic morpho-anatomical features
      that enable one to assign specimens to it without DNA sequence data, and it is
      the first subfamily to possess both Type 1 (Chamberlainium) and Type 2
      (Pneophyllum) tetra/bisporangial conceptacle roof development. Two characters
      distinguish Chamberlainium from Spongites: tetra/biasporangial conceptacle
      chamber diameter (<300 MUm in Chamberlainium vs. >300 MUm in Spongites) and
      tetra/bisporangial conceptacle roof thickness (<8 cells in Chamberlainium vs. >8
      cells in Spongites). Two characters also distinguish Pneophyllum from
      Dawsoniolithon: tetra/bisporangial conceptacle roof thickness (<8 cells in
      Pneophyllum vs. >8 cells in Dawsoniolithon) and thallus construction (dimerous in
      Pneophyllum vs. monomerous in Dawsoniolithon).

PMID- 29574891
TI  - Spotlight on small molecules in cardiovascular diseases.
AB  - LINKED ARTICLES: This article is part of a themed section on Spotlight on Small
      Molecules in Cardiovascular Diseases. To view the other articles in this section
      visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

PMID- 29574892
TI  - Codability of industry and occupation information from cancer registry records:
      Differences by patient demographics, casefinding source, payor, and cancer type.
AB  - INTRODUCTION: Industry and occupation (I&O) information collected by cancer
      registries is useful for assessing associations among jobs and malignancies.
      However, systematic differences in I&O availability can bias findings. METHODS:
      Codability by patient demographics, payor, identifying (casefinding) source, and
      cancer site was assessed using I&O text from first primaries diagnosed 2011-2012
      and reported to California Cancer Registry. I&O were coded to a U.S. Census code
      or classified as blank/inadequate/unknown, retired, or not working for pay.
      RESULTS: Industry was codable for 37% of cases; 50% had "unknown" and 9%
      "retired" instead of usual industry. Cases initially reported by hospitals,
      covered by preferred providers, or with known occupational etiology had highest
      codable industry; cases from private pathology laboratories, with Medicaid, or
      diagnosed in outpatient settings had least. Occupation results were similar.
      CONCLUSIONS: Recording usual I&O for retirees and improving linkages for
      reporting entities without patient access would improve I&O codability and
      research validity.

PMID- 29574893
TI  - Adverse drug event profile associated with pregabalin among patients with and
      without cancer: analysis of a spontaneous reporting database.
AB  - WHAT IS KNOWN AND OBJECTIVE: Pregabalin is used for the relief of neuropathic
      pain in patients with and without cancer. However, no report has examined whether
      there is a difference in the adverse drug event (ADE) profile of pregabalin in
      each context. We aimed to establish whether pregabalin's ADE profile was
      different between patients with and without cancer. This study was based on the
      Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous
      reporting database. METHOD: Reports obtained from the JADER database were
      analysed from April 2004 to December 2016 for ADEs, using reporting odds ratios
      (RORs), a method of disproportionality analysis. We evaluated the association
      between the RORs and ADEs of pregabalin and compared the age, dosage and time at
      which ADEs occurred in patients with and without cancer. The primary outcome was
      RORs. Secondary outcomes were expression age and time-to-onset of ADE among
      patients with and without cancer. RESULTS AND DISCUSSION: In total, 426 216
      reports from the JADER database were analysed. The major side effects associated
      with pregabalin among both patient groups were interstitial pneumonia, renal
      failure, liver failure, altered consciousness, heart failure and rhabdomyolysis.
      The pregabalin dose was significantly higher in patients with cancer than in
      those without cancer. Furthermore, the times to reporting of interstitial
      pneumonia, altered consciousness and liver failure were significantly shorter in
      patients with cancer than in those without cancer. WHAT IS NEW AND CONCLUSION:
      The ADE profiles of pregabalin were broadly similar among patients with and
      without cancer, but time-to-onset and type of some ADEs may be different.

PMID- 29574894
TI  - Irreproducible text-book "knowledge": The effects of color bands on zebra finch
      fitness.
AB  - Many fields of science-including behavioral ecology-currently experience a heated
      debate about the extent to which publication bias against null findings results
      in a misrepresentative scientific literature. Here, we show a case of an extreme
      mismatch between strong positive support for an effect in the literature and a
      failure to detect this effect across multiple attempts at replication. For
      decades, researchers working with birds have individually marked their study
      species with colored leg bands. For the zebra finch Taeniopygia guttata, a model
      organism in behavioral ecology, many studies over the past 35 years have reported
      effects of bands of certain colors on male or female attractiveness and further
      on behavior, physiology, life history, and fitness. Only eight of 39 publications
      presented exclusively null findings. Here, we analyze the results of eight
      experiments in which we quantified the fitness of a total of 730 color-banded
      individuals from four captive populations (two domesticated and two recently wild
      derived). This sample size exceeds the combined sample size of all 23
      publications that clearly support the "color-band effect" hypothesis. We found
      that band color explains no variance in either male or female fitness. We also
      found no heterogeneity in color-band effects, arguing against both context and
      population specificity. Analysis of unpublished data from three other
      laboratories strengthens the generality of our null finding. Finally, a meta
      analysis of previously published results is indicative of selective reporting and
      suggests that the effect size approaches zero when sample size is large. We argue
      that our field-and science in general-would benefit from more effective means to
      counter confirmation bias and publication bias.

PMID- 29574895
TI  - "Not such a kid thing anymore": Young adults' perspectives on transfer from
      paediatric to adult cardiology care.
AB  - BACKGROUND: Transfer of adolescents with congenital heart disease from paediatric
      cardiology providers to specialized adult congenital heart disease (ACHD) care
      providers is becoming a standard practice. However, some paediatric cardiologists
      continue to provide care for their patients into adult life. Little is known
      about the perspectives of young adult patients who have been transferred to ACHD
      clinics versus those who continue to receive their cardiology care in paediatric
      settings. METHODS: Content and thematic analysis of structured telephone
      interviews with 21 young adults age 18-25 (13 transferred to ACHD clinic and 8
      who had not transferred) was conducted to identify similarities and differences
      in patient characteristics of those in ACHD versus paediatric settings. RESULTS:
      There were no appreciable differences in gender, age, heart disease type, and
      independence between those transferred to ACHD care versus those not transferred.
      Participants in both groups were aware of differences between the paediatric and
      ACHD care settings and providers, with some favouring the familiarity offered by
      the paediatric setting and providers. Participants had varying views on parental
      involvement in their care; most of them had attended clinic appointments on their
      own. Those who had transferred to ACHD care acknowledged that it would take time
      to adjust to new relationships. Positive perspectives on actual or anticipated
      transfer to ACHD care included a growing sense of autonomy and responsibility, as
      well as access to reproductive information relevant to ACHD patients.
      CONCLUSIONS: The absence of patient characteristics distinguishing those in ACHD
      care versus those still followed in paediatric care suggests that system,
      provider, and parent factors, rather than patient factors, may account for
      patients' perspectives on transfer to ACHD care.

PMID- 29574896
TI  - Resident hesitation in the operating room: does uncertainty equal incompetence?
AB  - CONTEXT: In postgraduate medical programmes, the progressive development of
      autonomy places residents in situations in which they must cope with uncertainty.
      We explored the phenomenon of hesitation, triggered by uncertainty, in the
      context of the operating room in order to understand the social behaviours
      surrounding supervision and progressive autonomy. METHODS: Nine surgical
      residents and their supervising surgeons at a Canadian medical school were
      selected. Each resident-supervisor pair was observed during a surgical procedure
      and subsequently participated in separate post-observation, semi-structured
      interviews. Constructivist grounded theory was used to guide the collection and
      analysis of data. RESULTS: Three hesitation-related themes were identified: the
      principle of progress; the meaning of hesitation, and the judgement of
      competence. Supervisors and residents understood hesitation in the context of a
      core surgical principle we termed the 'principle of progress'. This principle
      reflects the supervisors' and residents' shared norm that maintaining progress
      throughout a surgical procedure is of utmost importance. Resident hesitation was
      perceived as the first indication of a disruption to this principle and was
      therefore interpreted by supervisors and residents alike as a sign of
      incompetence. This interpretation influenced the teaching-learning process during
      these moments when residents were working at the edge of their abilities.
      CONCLUSIONS: The principle of progress influences the meaning of hesitation
      which, in turn, shapes judgements of competence. This has important implications
      for teaching and learning in direct supervision settings such as surgery. Without
      efforts to change the perception that hesitation represents incompetence, these
      potential teaching-learning moments will not fully support progressive autonomy.

PMID- 29574897
TI  - IL-6 increases podocyte motility via MLC-mediated focal adhesion impairment and
      cytoskeleton disassembly.
AB  - The disturbance of podocyte motility is an essential pathogenic mechanisms of
      foot process effacement during proteinuric diseases, and myosin light chain (MLC)
      is a pivotal component in regulating the motility of podocytes. Inflammatory
      cytokine interleukin-6 (IL-6) has been reported to induce podocyte abnormalities
      by various mechanisms, however, whether aberrant cell motility contributes to the
      IL-6-induced podocyte injury remains unknown. Here, by wound healing, transwell,
      and cell migration assays, we confirmed that IL-6 accelerates the motility of
      podocyte. Simultaneously, the phosphorylation of MLC is elevated along with
      perturbed focal adhesion (FAs) and cytoskeleton. Next, via genetic and
      pharmacologic interruption of MLC or its phosphorylation we revealed that the
      activation of MLC is implicated in IL-6-mediated podocyte hypermotility as well
      as the disassembly of FAs and F-actin. By using stattic, an inhibitor for STAT3
      phosphorylation, we uncovered that STAT3 activation is the upstream event for MLC
      phosphorylation and the following aberrant motility of podocytes. Additionally,
      we found that calcitriol markedly attenuates podocyte hypermotility via blocking
      STAT3-MLC. In conclusion, our study demonstrated that IL-6 interrupts FAs
      dynamic, cytoskeleton organization, and eventually leads to podocyte
      hypermotility via STAT3/MLC, whereas calcitriol exerts its protective role by
      inhibiting this pathway. These findings enrich the mechanisms accounting for IL-6
      mediated podocyte injury from the standpoint of cell motility and provide a novel
      therapeutic target for podocyte disorders.

PMID- 29574898
TI  - The frequency and management of seizures during psychological treatment among
      patients with psychogenic nonepileptic seizures and epilepsy.
AB  - OBJECTIVE: Growing evidence suggests that psychological treatments are effective
      for improving outcomes in both epilepsy and psychogenic nonepileptic seizures
      (PNES). However, the risk of in-session seizures may cause concerns about safety
      and about seizures disrupting treatment. This study explores the risk of in
      session seizures in patients with epilepsy and those with PNES, the timings of
      seizures during psychological therapy, and the responses of therapists to
      seizures. METHODS: Consecutive patients with epilepsy or PNES attending 2
      neurology centers in the United Kingdom for psychological treatment to help with
      their seizure disorders were studied. Information about seizures during
      outpatient psychological therapy sessions was gathered using a 12-item pro forma.
      RESULTS: Ninety-seven patients with epilepsy and 195 with PNES were evaluated.
      One in 32 patients with epilepsy and 1 in 8 with PNES had at least 1 in-session
      seizure. A seizure occurred in 1 in 136 treatment sessions provided to patients
      with epilepsy, and 1 in 36 sessions provided to those with PNES. The risk of in
      session seizures was significantly greater in patients with PNES than in patients
      with epilepsy (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.3-15.2).
      Seizures tended to occur in the first half of treatment programs and individual
      sessions and only disrupted sessions briefly. Only one patient with PNES required
      in-patient observation not involving overnight admission. SIGNIFICANCE: In
      session seizures do occur and are much more common in patients with PNES than in
      those with epilepsy. Seizures rarely caused major disruption to psychological
      treatment, and could almost invariably be managed by the treating therapist
      without help from additional medical staff. Nonetheless, this research suggests
      that psychological therapy providers should anticipate the occurrence of in
      session seizures and have safe management plans in place. The greater frequency
      of in-session seizures in PNES may add to our understanding of the mechanisms
      triggering these seizures.

PMID- 29574899
TI  - Ruxolitinib for steroid-refractory graft-versus-host disease: A case series.

PMID- 29574900
TI  - A Reliable Method for Quantification of Tendon Structure Using B-Mode Ultrasound.
AB  - Structure is an important clinical marker of tendon health; however, current
      standards use qualitative scores that are not strongly reliable. Therefore, the
      purpose of this study was to establish the reliability of an image-processing
      technique that quantifies tendon collagen structure using B-mode ultrasound
      images. Longitudinal images of the Achilles tendon were collected in 12 healthy
      young adults, and intra- and inter-rater reliability was assessed over multiple
      image selections and multiple days. Intraclass correlation coefficients were
      strong (r >= 0.71) for all comparisons. These findings demonstrate that
      quantitative assessments of tendon structure using B-mode ultrasound are
      reliable.

PMID- 29574901
TI  - Effects of organ motion on proton prostate treatments, as determined from
      analysis of daily CT imaging for patient positioning.
AB  - PURPOSE: We quantified interfractional movements of the prostate, seminal
      vesicles (SVs), and rectum during computed tomography (CT) image-guided proton
      therapy for prostate cancer and studied the range variation in opposed lateral
      proton beams. MATERIALS/METHODS: We analyzed 375 sets of daily CT images acquired
      throughout the proton therapy treatment of ten patients. We analyzed daily
      movements of the prostate, SVs, and rectum by simulating three image-matching
      strategies: bone matching, prostate center (PC) matching, and prostate-rectum
      boundary (PRB) matching. In the PC matching, translational movements of the
      prostate center were corrected after bone matching. In the PRB matching, we
      performed PC matching and correction along the anterior-posterior direction to
      match the boundary between the prostate and the rectum's anterior region. In each
      strategy, we evaluated systematic errors (Sigma) and random errors (sigma) by
      measuring the daily movements of certain points on each anatomic structure. The
      average positional deviations in millimeter of each point were determined by the
      Van Herk formula of 2.5Sigma + 0.7sigma. Using these positional deviations, we
      created planning target volumes of the prostate and SVs and analyzed the daily
      variation in the water equivalent length (WEL) from the skin surface to the
      target along the lateral beam directions using the density converted from the
      daily CT number. Based on this analysis, we designed prostate cancer treatment
      planning and evaluated the dose volume histograms (DVHs) for these strategies.
      RESULTS: The SVs' daily movements showed large variations over the superior
      inferior direction, as did the rectum's anterior region. The average positional
      deviations of the prostate in the anterior, posterior, superior, inferior, and
      lateral sides (mm) in bone matching, PC matching, and PRB matching were (8.9,
      9.8, 7.5, 3.6, 1.6), (5.6, 6.1, 3.5, 4.5, 1.9), and (8.6, 3.2, 3.5, 4.5, 1.9)
      (mm), respectively. Moreover, the ones of the SV tip were similarly (22.5, 15.5,
      11.0, 7.6, 6.0), (11.8, 8.4, 7.8, 5.2, 6.3), and (9.9, 7.5, 7.8, 5.2, 6.3). PRB
      matching showed the smallest positional deviations at all portions except for the
      anterior portion of the prostate and was able to markedly reduce the positional
      deviations at the posterior portion. The averaged WEL variations at the distal
      and proximal sides of planning target volumes were estimated 7-9 mm and 4-6 mm,
      respectively, and showed the increasing of a few millimeters in PC and PRB
      matching compared to bone matching. In the treatment planning simulation, the DVH
      values of the rectum in PRB matching were reduced compared to those obtained with
      other matching strategies. CONCLUSION: The positional deviations for the prostate
      on the posterior side and the SVs were smaller by PRB matching than the other
      strategies and effectively reduced the rectal dose. 3D dose calculations indicate
      that PRB matching with CT image guidance may do a better job relative to other
      positioning methods to effectively reduce the rectal complications. The WEL
      variation was quite large, and the appropriate margin (approx. 10 mm) must be
      adapted to the proton range in an initial planning to maintain the coverage of
      target volumes throughout entire treatment.

PMID- 29574902
TI  - FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.
AB  - Angiogenesis is a critical aspect of wound healing. We investigated the role of
      keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of
      the transcription factor FOXO1. The results indicate that keratinocyte-specific
      deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads
      to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re
      epithelialization and granulation tissue formation. In vitro FOXO1 was needed for
      VEGFA transcription and expression. In a porcine dermal wound-healing model that
      closely resembles healing in humans, local application of a FOXO1 inhibitor
      reduced angiogenesis. This is the first report that FOXO1 directly regulates
      VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound
      healing. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd.

PMID- 29574903
TI  - James Melius, MD, DrPH, 1948-1918.

PMID- 29574904
TI  - Respiratory disease and sero-epidemiology of respiratory pathogens in the working
      horses of Ethiopia.
AB  - BACKGROUND: Pathogens are frequently implicated in equine respiratory disease. In
      Ethiopia, respiratory disease is a frequent cause for presentation at veterinary
      clinics and a priority concern for users of working horses. However, there is
      little existing literature on possible aetiologies. OBJECTIVES: Determine
      prevalence of respiratory signs and exposure to major respiratory pathogens
      through a serological survey. STUDY DESIGN: Cross-sectional. METHODS:
      Systematically selected horses from 19 sites in central Ethiopia were examined
      clinically and sampled once (August-December 2013). A face-to-face interview
      collected data on horses' management and history. Serological testing targeted
      equine influenza virus (EIV), equine herpesviruses-1 (EHV-1) and -4 (EHV-4),
      equine rhinitis viruses A (ERAV) and B (ERBV), equine arteritis virus (EAV) and
      Streptococcus equi subspecies equi (S. equi). RESULTS: Owners reported a recent
      history of coughing in 38% of horses and nasal discharge in 7%. No animals were
      observed coughing during examination but 6% had a nasal discharge. Antibodies
      towards S. equi, were most prevalent (8%, 33/350). Antibodies to EAV were
      confirmed in one animal (0.3%). Low antibody titres to EHV-1/4 and ERA/BV
      suggested prior exposure but antibodies to EIV were not detected. Multivariable,
      multilevel logistic regression analysis for risk factors associated with S. equi
      serostatus showed higher odds of seropositivity in younger animals and those
      working less frequently. MAIN LIMITATIONS: A single serological sample cannot
      describe dynamic changes in antibodies. Sampling horses at the place of work may
      result in healthy-worker bias. CONCLUSIONS: S. equi may be endemic in this
      population and contributing, in part, to the occurrence of respiratory disease.
      Low prevalence of antibodies to viruses, with the exception of EIV, indicates
      these pathogens are present, but unlikely a predominant cause of respiratory
      signs and noninfectious causes of disease should also be investigated. Working
      horses in this region would be vulnerable to incursion of equine influenza.

PMID- 29574905
TI  - Parents' perceptions of the long-term appropriateness of a psychosocial
      intervention for children with attention deficit hyperactivity disorder.
AB  - BACKGROUND/AIM: Designing psychosocial interventions that parents perceive as
      appropriate is essential to enhancing their engagement with the intervention and
      their long-term use of the intervention strategies. The aim of this study was to
      explore the long-term appropriateness of a play-based psychosocial intervention
      for children with Attention Deficit Hyperactivity Disorder (ADHD) from the
      perspectives of parents. METHODS: Semi-structured phone interviews were conducted
      with 14 parents of children with ADHD who participated in a randomised controlled
      trial of the play-based intervention 1 year earlier. RESULTS: Thematic analysis
      led to the development of three core-themes: (i) Everybody needs a parenting
      handbook, (ii) No one thing you are dealing with, and (iii) A different approach:
      Reframing. DISCUSSION: The core-themes related back to a definition of
      intervention appropriateness that acknowledges the intervention as
      important/relevant, beneficial, socially and ecologically valid and promotes
      sustainable change, indicating parents perceived the intervention as appropriate.
      The core-themes also resembled aspects of the process of family adaptation.
      Findings highlight the importance of designing interventions that are appropriate
      from parents' perspectives to enhance their long-term engagement and use of the
      intervention strategies as well as outcomes for their child in the long term.

PMID- 29574906
TI  - The in vitro antimicrobial evaluation of commercially essential oils and their
      combinations against acne.
AB  - OBJECTIVE: The study investigated the efficacy of commercial essential oil
      combinations against the two pathogens responsible for acne with the aim to
      identify synergy and favourable oils to possibly use in a blend. MATERIALS AND
      METHODS: Antimicrobial activity was assessed using the minimum inhibitory
      concentration (MIC) assay against Staphylococcus epidermidis (ATCC 2223) and
      Propionibacterium acnes (ATCC 11827), and the fractional inhibitory concentration
      index (SigmaFIC) was calculated. Combinations displaying synergistic interactions
      were further investigated at varied ratios and the results plotted on
      isobolograms. RESULTS: From the 408 combinations investigated, 167 combinations
      were identified as displaying noteworthy antimicrobial activity (MIC value <=1.00
      mg mL-1 ). Thirteen synergistic interactions were observed against S.
      epidermidis, and three synergistic combinations were observed against P. acnes.
      It was found that not one of the synergistic interactions identified were based
      on the combinations recommended in the layman's aroma-therapeutic literature.
      Synergy was evident rather from leads based on antimicrobial activity from
      previous studies, thus emphasizing the importance of scientific validation.
      Leptospermum scoparium J.R.Forst. and G.Forst (manuka) was the essential oil
      mostly involved in synergistic interactions (four) against S. epidermidis.
      Cananga odorata (Lam.) Hook.f. and Thomson (ylang ylang) essential oil was also
      frequently involved in synergy where synergistic interactions could be observed
      against both pathogens. The combination with the lowest MIC value against both
      acne pathogens was Vetiveria zizanioides Stapf (vetiver) with Cinnamomum verum
      J.Presl (cinnamon bark) (MIC values 0.19-0.25 mg mL-1 ). Pogostemon patchouli
      Benth. (patchouli), V. zizanioides, C. verum and Santalum spp. (sandalwood) could
      be identified as the oils that contributed the most noteworthy antimicrobial
      activity towards the combinations. The different chemotypes of the essential oils
      used in the combinations predominantly resulted in similar antimicrobial
      activity. CONCLUSIONS: The investigated essential oil combinations resulted in at
      least 50% of the combinations displaying noteworthy antimicrobial activity. Most
      of the synergistic interactions do not necessarily correspond to the recommended
      layman's aroma-therapeutic literature, which highlights a need for scientific
      validation of essential oil antimicrobial activity. No antagonism was observed.

PMID- 29574907
TI  - Inventing a new measurement for inhibitory control in preschoolers.
AB  - One of the most prominent tasks to measure spatial-conflict inhibitory control in
      preschoolers is the windows task (Russell et al., 1991, Br. J. Dev. Psychol., 9,
      331). However, this task has been criticized given its high demands on abilities
      other than inhibition. The aim of the current set of studies was to establish the
      'car task' as a novel instrument to assess conflict inhibition in children. In
      this task, children are asked to point at the current location of an occluded
      object. To do so, they have to inhibit a misleading colour cue in front of the
      locations in critical trials. In Study 1, we demonstrated that 3- to 6-year-old
      children's (N = 88) performance in the car task correlated positively with that
      in the windows task (even after controlling for age). Study 2 investigated
      whether children's failure in the car task might be caused by their inability to
      master the basic processes involved in the task rather than a lack of inhibition.
      We presented a new group of preschoolers (N = 85) with a modified version of the
      task without any misleading colour cues. Performance significantly improved,
      indicating that the difficulty of the car task lies in the necessity to inhibit
      the misleading colour cue leading towards the incorrect location. These findings
      suggest that the car task is a valid measurement of spatial-conflict inhibition
      in children. Statement of contribution What is already known on this subject?
      Inhibitory control (IC) is important for action planning and execution. One of
      the most prominent measurements of spatial-conflict IC is the windows task. This
      task has been criticized for additionally requiring rule inference to succeed.
      What does this study adds? Performance in the novel car task correlates with that
      in the windows task. Study 2 controls for demands other than IC such as memory or
      task difficulty. This task can thus be used to measure IC more purely without
      demanding rule inference.

PMID- 29574908
TI  - Peroxisome proliferator-activated receptor gamma plays dual roles on experimental
      periodontitis in rats.
AB  - AIM: To investigate the effects of peroxisome proliferator-activated receptor
      gamma (PPARgamma) on inflammation control and bone remodelling in experimental
      periodontitis in rats. MATERIALS AND METHODS: Experimental periodontitis was
      induced in rats by thread ligation around cervixes of mandibular first molars.
      PPARgamma agonist, antagonist and vehicle were intraperitoneally administrated,
      respectively, into rats. Ninety-six male SD rats were randomly divided into
      control, ligation + vehicle, ligation + agonist and ligation + antagonist groups.
      After 1, 4 and 8 weeks, alveolar bone loss was assessed by Micro-CT and HE
      staining. Inflammation and bone metabolism factors were evaluated by ELISA and
      immunohistochemical examination. Osteoclasts were quantified by tartrate
      resistant acid phosphatase (TRAP) staining. RESULTS: Alveolar bone loss was
      significantly reduced after 1 week, while significantly increased after 8 weeks
      in agonist group, but antagonist group showed the opposite trend. Agonist
      decreased some inflammatory cytokines expression after 1 and 4 weeks,
      downregulated OPG, RUNX2, BMP-2 and upregulated RANKL after 8 weeks, but
      antagonist brought the opposite effect. PPARgamma agonist significantly reduced
      osteoclast counting after 1 week, while increased it after 8 weeks. CONCLUSIONS:
      During periodontitis progression, PPARgamma could inhibit inflammation, prevent
      bone resorption within a short time, while the long-term PPARgamma activation
      would lead to increased bone resorption, and PPARgamma repression by antagonist
      would enhance alveolar bone formation.

PMID- 29574909
TI  - Iron status in relation to cancer risk and mortality: Findings from a population
      based prospective study.
AB  - While experimental evidence suggests potential carcinogenic effects of increased
      iron load, there is a lack of data on iron status and cancer risk from
      epidemiological studies. Here, we evaluated prediagnostic serum concentrations of
      ferritin, iron and transferrin as well as transferrin saturation (TSAT) in
      relation to cancer risk and mortality in a prospective study by multivariable Cox
      regression analyses. A case-cohort sample of the population-based EPIC-Heidelberg
      Study including a random subcohort (n = 2738) and incident cases of breast cancer
      (n = 627), prostate cancer (n = 554), lung cancer (n = 195), colorectal cancer (n
      = 256) and cancer death (n = 759) was used. Ferritin levels were inversely
      associated with breast cancer risk in the multivariable Cox regression model,
      with a hazard ratio (HR) of 0.67 [95% confidence interval: 0.49, 0.92] for women
      in the highest quartile compared to those in the lowest quartile. Neither
      ferritin nor the other markers of iron status were significantly associated with
      colorectal, prostate or lung cancer risk. An inverse association was observed
      between ferritin and total cancer mortality (HR: 0.70 [0.53, 0.92]). There were
      no significant overall associations between serum iron, transferrin or TSAT and
      cancer mortality. The present findings do not support the notion of increased
      iron load constituting a cancer risk factor in the general population. By
      contrast, our analyses revealed inverse associations between ferritin levels and
      breast cancer risk as well as cancer mortality.

PMID- 29574910
TI  - Contemporary Definitions of Suicidal Behavior: A Systematic Literature Review.
AB  - To address the lack of comparability around the world, we conducted a systematic
      review of existing definitions of suicide and suicidal behaviors. In the
      literature, four key features appear to cover the vast majority of concepts
      underpinning definitions: agency, knowledge of a potential fatal outcome, intent,
      and outcome. Intent and outcome appear to be the most consensual features of
      definitions of suicide, albeit revealing interesting conceptual variations. The
      four key features could be used to devise a research tool able to explore the
      meanings of suicide across different countries and different cultures.

PMID- 29574911
TI  - Long noncoding RNAs in cancer-immunity cycle.
AB  - The imbalance of immune status in cancer microenvironment plays an important role
      in the development and progression of cancer. Immunotherapy based on this has
      become an important field of cancer research in recent years. Many studies on
      long noncoding RNA (lncRNA) in cancer have focus on its regulation in cancer
      development and metastasis. Recent studies have suggested that lncRNAs play
      crucial roles in different phases of cancer immunity, including antigen
      releasing, antigen presentation, immune activation, immune cells migration,
      infiltrating into cancer tissues, and killing cancer cells. The functional
      studies of lncRNAs in cancer immuntity revealed the complicated molecular
      mechanisms in cancer immunity from a new point of view, which may provide novel
      potential targets for cancer immunotherapies. Based on the classical cancer
      immunity cycle theory, we review the recent studies on the functions and
      mechanisms of immune-related lncRNAs in different stages of cancer immunity, to
      summarize the relationship between lncRNAs, and cancer immunity and to provide a
      framework for further research.

PMID- 29574912
TI  - Evaluation of the fetal palate at 11 to 13 (+6) weeks of gestation based on an
      analysis of static ultrasound images using modern IT techniques.
AB  - OBJECTIVE: To describe a new computer-based technique to isolate the shape of the
      fetal palate visible in the midsagittal plane from static ultrasound images
      routinely used to measure nuchal translucency. METHOD: This is a retrospective
      interpretation of images of the midsagittal view of the fetal face at 11 to 13
      (+6) weeks of gestation in 7 cases of cleft lip and palate (CLP) and 7 normal
      controls. The images were subjected to pattern analysis. RESULTS: Proprietary
      software was applied and for each CLP case, and palatine bones with different
      forms from those of fetuses in the control group were recorded. In 4 cases, an
      image of a continuous palatine bone was observed at a threshold of 180, whereas
      the remaining 3 images were obtained at 128. A continuous palatine bone structure
      was not observed in any fetus from the CLP group, even at a level of 128, when
      the surrounding structures were visible. CONCLUSION: The application of pattern
      analysis to a 2D frozen image is a new approach for prenatal diagnostics. This
      technique may be a helpful tool for physicians and could assist in the diagnosis
      of cleft palate.

PMID- 29574913
TI  - Shear Wave Elastography to Assess False Vocal Folds in Healthy Adults: A
      Feasibility Study.
AB  - OBJECTIVES: The aim of the study was to investigate the feasibility of using
      ultrasound shear wave elastography to quantify mechanical properties and movement
      symmetry of false vocal folds positioned in adduction and abduction. METHODS: We
      prospectively measured the shear wave velocity (SWV) within the bilateral false
      vocal folds in 10 healthy adults using acoustic radiation force impulse imaging.
      From a transcutaneous approach at the level of thyroid cartilage, 5 SWV
      measurements were obtained within each side of the false vocal folds twice in
      adduction and again in abduction for each participant. Configuration-related
      differences in the SWV within false vocal folds were compared between adduction
      and abduction, in addition to differences between the right and left false vocal
      folds and between men and women, by a paired t test. We developed an SWV index
      [(SWVgreater - SWVlesser )/SWVgreater ] to assess movement symmetry between the
      right and left false vocal folds. Intraobserver agreement on repeated measures
      was examined by the intraclass correlation coefficient. RESULTS: The 10
      participants included 5 men and 5 women. We observed that the SWV within false
      vocal folds was significantly higher in adduction than in abduction (P < .001).
      The SWV within false vocal folds in adduction was also significantly higher in
      women compared to men (P < .001). There was no significant difference in the SWV
      between the right and left false vocal folds in adduction or in abduction or
      between men and women in abduction (P > .05). The mean SWV index was 0.05 (range,
      0.03-0.07). The intraclass correlation coefficient for intraobserver agreement
      was 0.89 (P < .001). CONCLUSIONS: Shear wave elastography seems to be feasible to
      quantify mechanical properties and evaluate the symmetry of false vocal folds in
      healthy adults.

PMID- 29574914
TI  - Case of renal metastasis of melanoma successfully controlled by a combination
      therapy of nivolumab and radiation.

PMID- 29574915
TI  - Cyclophosphamide versus etoposide in combination with total body irradiation as
      conditioning regimen for adult patients with Ph-negative acute lymphoblastic
      leukemia undergoing allogeneic stem cell transplant: On behalf of the ALWP of the
      European Society for Blood and Marrow Transplantation.
AB  - Allogeneic hematopoietic cell transplantation (alloHCT) with myeloablative
      conditioning based on total body irradiation (TBI) is widely used for the
      treatment of adults with acute lymphoblastic leukemia (ALL). TBI is most
      frequently administered in combination with either cyclophosphamide (Cy/TBI) or
      etoposide (Vp/TBI). The goal of this study was to retrospectively compare these
      two regimens. Adult patients with Ph-negative ALL treated with alloHCT in first
      or second complete remission who received Cy/TBI (n = 1346) or Vp/TBI (n = 152)
      conditioning were included in the analysis. In a univariate analysis, as compared
      to Cy/TBI, the use of Vp/TBI was associated with reduced incidence of relapse
      (17% vs. 30% at 5 years, P = .007), increased rate of leukemia-free survival (60%
      vs. 50%, P = .04), and improved "graft versus host disease (GVHD) and relapse
      free survival" (GRFS, 43% vs. 33%, P = .04). No significant effect could be
      observed in terms of the incidence of nonrelapse mortality or acute or chronic
      GVHD. In a multivariate model, the use of Vp/TBI was associated with reduced risk
      of relapse (HR = 0.62, P = .04) while the effect on other study end-points was
      not significant. In conclusion, conditioning regimen based on Vp combined with
      TBI appears more effective for disease control than the combination of Cy with
      TBI for adult patients with Ph-negative ALL treated with alloHCT.

PMID- 29574916
TI  - Determinants of change in home participation among critically ill children.
AB  - AIM: To estimate changes in home participation among critically ill children in
      the first 6 months after discharge from a pediatric intensive care unit (PICU),
      and to explore the effect of child, service, and environmental factors on change
      in home participation. METHOD: This was a prospective bi-center, longitudinal
      cohort study. Caregivers of 180 children, aged 1 to 17 years, who were admitted
      into the PICU for at least 48 hours were included. Patient-reported outcomes were
      used to capture caregivers' perspectives of their child's participation and
      environmental supports for participation in home activities. Data were collected
      at enrollment, and 3 and 6 months after discharge. RESULTS: There were no
      significant changes in home participation frequency or involvement, but
      involvement rates across time were moderated by functional status. Age
      significantly predicted participation frequency. Pre-PICU functional status and
      capabilities were significant predictors of participation frequency and
      involvement, and home environmental support significantly predicted home
      involvement. INTERPRETATION: Results suggest relatively stable participation
      trajectories in the 6 months after PICU admission. Children with abnormal
      baseline function experienced a greater increase in home involvement after PICU.
      Rehabilitation interventions targeting functional capabilities and home
      environment may be viable approaches during the early phase of recovery.
      Environmental interventions may be more time-efficient after PICU stay and merit
      further study. WHAT THIS PAPER ADDS: Children's pre-pediatric intensive care unit
      (PICU) functional status and capabilities impact their participation after
      critical illness. Children's trajectories of home involvement may differ over
      time based on their pre-PICU functional status. Caregiver perceptions of
      environmental support impact a child's home involvement after discharge from a
      PICU.

PMID- 29574917
TI  - The tracheal system in post-embryonic development of holometabolous insects: a
      case study using the mealworm beetle.
AB  - The tracheal (respiratory) system is regarded as one of the key elements which
      enabled insects to conquer terrestrial habitats and, as a result, achieve extreme
      species diversity. Despite this fact, anatomical data concerning this biological
      system is relatively scarce, especially in an ontogenetic context. The purpose of
      this study is to provide novel and reliable information on the post-embryonic
      development of the tracheal system of holometabolous insects using micro-computed
      tomography methods. Data concerning the structure of the respiratory system
      acquired from different developmental stages (larvae, pupae and adults) of a
      single insect species (Tenebrio molitor) are co-analysed in detail. Anatomy of
      the tracheal system is presented. Sample sizes used (29 individuals) enabled
      statistical analysis of the results obtained. The following aspects have been
      investigated (among others): the spiracle arrangement, the number of tracheal
      ramifications originating from particular spiracles, the diameter of longitudinal
      trunks, tracheal system volumes, tracheae diameter distribution and fractal
      dimension analysis. Based on the data acquired, the modularity of the tracheal
      system is postulated. Using anatomical and functional factors, the following
      respiratory module types have been distinguished: cephalo-prothoracic,
      metathoracic and abdominal. These modules can be unambiguously identified in all
      of the studied developmental stages. A cephalo-prothoracic module aerates organs
      located in the head capsule, prothorax and additionally prolegs. It is
      characterised by relatively thick longitudinal trunks and originates in the first
      thoracic spiracle pair. Thoracic modules support the flight muscles, wings,
      elytra, meso- and metalegs. The unique feature of this module is the presence of
      additional longitudinal connections between the neighbouring spiracles. These
      modules are concentrated around the second prothoracic and the first abdominal
      spiracle pairs. An abdominal module is characterised by relatively thin ventral
      longitudinal trunks. Its main role is to support systems located in the abdomen;
      however, its long visceral tracheae aerate organs situated medially from the
      flight muscles. Analysis of changes of the tracheal system volume enabled the
      calculation of growth scaling among body tissues and the volume of the tracheal
      system. The data presented show that the development of the body volume and
      tracheal system is not linear in holometabola due to the occurrence of the pupal
      stage causing a decrease in body volume in the imago and at the same time
      influencing high growth rates of the tracheal system during metamorphosis,
      exceeding that ones observed for hemimetabola.

PMID- 29574918
TI  - Ginsenoside Rb1 inhibits autophagy through regulation of Rho/ROCK and PI3K/mTOR
      pathways in a pressure-overload heart failure rat model.
AB  - OBJECTIVE: This study was designed to explore the relationship between
      ginsenoside Rb1 (Grb1) and high-load heart failure (HF) in rats. METHODS: The
      parameters of cardiac systolic function (left ventricular posterior wall
      thickness (LVPWT), left ventricular internal diastolic diameter (LVID), fraction
      shortening (FS) and mitral valves (MVs)) of rat hearts in each group were
      inspected by echocardiogram. The expressions of rat myocardial contractile
      proteins, autophagy-related proteins and the activation of Rho/ROCK and PI3K/mTOR
      pathways were detected by Western blot. KEY FINDINGS: LVPWT, FS, MVs and the
      expression of myocardial contractile proteins alpha-MHC, apoptosis-related
      proteins Bcl-2 and signalling pathway involved proteins pAkt and mTOR were
      significantly reduced in the HF, HF+5 mg/kg Grb1 (HF+Grb1-5) and
      HF+Grb1+arachidonic acid (AA) groups with LVID, beta-MHC, cell apoptosis, cell
      autophagy and Rho/ROCK significantly increased compared with the control group,
      of which the tendency was contrary to the HF+20 mg/kg Grb1 (HF+Grb1-20) group
      compared with the HF group (P < 0.05). In the HF+Grb1+AA group, there was no
      significant change in the above indexes compared with the HF group. CONCLUSIONS:
      The results indicated that Grb1 can exert anti-HF function by inhibiting
      cardiomyocyte autophagy of rats through regulation of Rho/ROCK and PI3K/mTOR
      pathways.

PMID- 29574919
TI  - Determining the evolutionary forces shaping G * E.
AB  - Contents Summary 31 I. Introduction 31 II. The maintenance of genetic variation
      for plasticity 32 III. Why is there environmental variation for genetic effects?
      33 IV. Conclusions 35 Acknowledgements 35 References 35 SUMMARY: Phenotypic
      plasticity is common in nature, yet we lack a comprehensive understanding of the
      evolutionary forces that shape genetic variation for plasticity. This endeavor is
      especially important because variation for plasticity will result in genotype-by
      environment interactions (G * E), a crucial component of variation in
      quantitative traits. Here, I review our understanding of the evolutionary forces
      shaping G * E, focusing specifically on: what evolutionary forces maintain
      variation for plasticity; and what forces maintain different genetic
      architectures across environments. My specific goal is to show that genomic data
      can be leveraged to explain the maintenance of G * E by contrasting patterns of
      genetic variation for plasticity with neutral expectations.

PMID- 29574920
TI  - Transcutaneous electrical stimulation on the anterior neck region: The impact of
      pulse duration and frequency on maximum amplitude tolerance and perceived
      discomfort.
AB  - Maximum amplitude tolerance (MAT) has been known as a primary factor determining
      the depth of electrical current penetration. However, the effect of varying
      transcutaneous electrical stimulation (TES) parameters on MAT and discomfort
      level is poorly understood. Furthermore, limited information exists regarding the
      biopsychological factors that may impact MAT and discomfort. The primary aims of
      this study were to compare the effects TES protocol with varying levels of pulse
      duration (300 MUs vs 700 MUs) and frequency (30 Hz vs 80 Hz) on the MAT and
      discomfort in healthy older adults. The exploratory aim of this study was to
      examine relationships between submental adipose tissue thickness, pain
      sensitivity and gender with MAT and discomfort. Twenty-four healthy older adults
      participated in this study. Transcutaneous electrical stimulation was delivered
      to the submental region. Maximum amplitude tolerance and discomfort were measured
      for each condition. Furthermore, submental adipose tissue thickness and pain
      sensitivity were measured for each subject. Maximum amplitude tolerance was
      significantly increased for the TES protocols with short-pulse duration [F (3,
      69) = 38.695, P < .0001]. Discomfort was similar across different TES protocols.
      Submental adipose tissue thickness (r = .30, P < .003) and pain sensitivity (r = 
      .43, P < .0001) were related to MAT. Pain sensitivity rating was also related to
      discomfort (r = .45, P < .0001). In conclusion, using TES protocols with short
      pulse duration may increase the MAT. Higher amplitude stimulation may increase
      the impact on deep swallowing muscles. In addition, submental adipose tissue
      thickness and pain sensitivity are potential biopsychological factors that may
      affect MAT and discomfort.

PMID- 29574921
TI  - Naturally occurring antiviral drug resistance in HIV patients who are mono
      infected or co-infected with HBV or HCV in China.
AB  - Drug resistance mutations (DRMs) may reduce the efficacy of antiviral therapy.
      However, the studies focused on naturally occurring, pre-existing DRMs among co
      infected patients in China are limited. To investigate DRMs prevalence in
      treatment-naive human immunodeficiency virus (HIV), hepatitis B virus (HBV), and
      hepatitis C virus (HCV) mono- and co-infected patients in China, a total of 570
      patients were recruited for this study. DRMs sequences were amplified and
      successfully sequenced in 481 of these patients, who were grouped into three
      cohorts: (i) The HBV cohort included 100 HIV/HBV co-infected and 110 HBV mono
      infected patients who were sequenced for HBV; (ii) The HCV cohort included 91
      patients who were HIV/HCV co-infected and 72 who were HCV mono-infected for HCV
      sequencing; and (iii) The HIV cohort included 39 HIV mono-infected, 22 HIV/HCV,
      and 47 HIV/HBV co-infected patients for HIV sequencing. Next-generation
      sequencing and Sanger sequencing were used in this study. The results showed that
      in the HCV cohort, HCV genotypes 6a (P < 0.001) and 3b (P = 0.004) were more
      prevalent in HIV/HCV co-infected patients, however, the prevalence of HBV and HIV
      genotypes were similar within the HBV and HIV cohorts. HBV DRMs prevalence was
      significantly higher in HIV/HBV co-infected than HBV mono-infected patients (8.0%
      vs 0.9%, P = 0.015), whereas HCV and HIV DRMs did not differ within the HCV and
      HIV cohort (P > 0.05). This study revealed that HBV DRMs were more prevalent in
      HIV/HBV co-infected patients in China, while DRMs in HCV and HIV patients did not
      differ. Further dynamic surveillance of DRMs may be needed.

PMID- 29574923
TI  - DNA methylation level of spermatozoa from subfertile and proven fertile and its
      relation to standard sperm parameters.
AB  - The epigenetic mechanism plays an important role in spermatogenesis such as DNA
      methylation where this episode is represented by either switching genes on or
      off. Twenty-eight samples (14 case and 14 controls) were subjected to Infinium
      450K BeadChip arrays to identify genomic regions that differ in sperm DNA
      methylation patterns in the subfertile compared to the proven fertile group. Then
      two CpGs were validated by deep bisulphite sequencing on 82 sperm samples. The
      results screening study revealed eight CpGs were significantly different in their
      sperm DNA methylation levels between cases and control group. The results of the
      validation study for the two CpGs (cg19779893 and cg19406113) showed that a
      significant variation in the methylation level at 2 CpGs of 3 CpGs related to
      cg19779893 site amplicon in cases compared to the controls. Moreover, six CpGs
      related to the cg19406113 site amplicon showed significant differences in sperm
      DNA methylation between the cases and the control group. Furthermore, there was a
      significant decrease in the sperm parameters in the cases compared to the control
      group. This study found two CpGs altered in their sperm DNA methylation levels.
      In addition, a strong association was found between changes in the sperm DNA
      methylation levels in these CpGs sites and sperm parameters.

PMID- 29574922
TI  - Transitioning patients with immune thrombocytopenia to second-line therapy:
      Challenges and best practices.
AB  - In patients with immune thrombocytopenia who do not adequately respond to first
      line therapy, there is no clear consensus on which second-line therapy to
      initiate and when. This situation leads to suboptimal approaches, including
      prolonged exposure to treatments that are not intended for long-term use (eg,
      corticosteroids) and overuse of off-label therapies (eg, rituximab) while
      approved, more efficacious options exist. These approaches may not only fail to
      address symptoms and burden of disease, but may also worsen health-related
      quality of life. A better understanding of available second-line treatments may
      ensure best use of therapeutic options and thereby optimize patient outcomes.

PMID- 29574924
TI  - The effects of transient receptor potential channel (TRPC) on airway smooth
      muscle cell isolated from asthma model mice.
AB  - This study aimed to validate whether transient receptor potential channel1
      (TRPC1) and TRPC3 participate in the regulation the proliferation of airway
      smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+ ) influx in
      vitro. Chronic model of murine asthma was induced and ASMCs isolated from
      asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in
      asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration
      and the cell viability of asthmatic mouse ASMCs were significantly higher than
      that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated
      these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca2+
      concentration and significantly induced the viability of ASMCs; whereas TRPC1 or
      TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of
      TRPC1 and TRPC3 also exerted different effects on the protein expression of
      growth-related proteins p-p38, p-JNK, cleaved caspase-3 and Bcl-2, as well as on
      cell cycle. Finally, we found Ca2+ chelator EGTA or BAPTA-AM significantly
      diminished the effects of si-TRPC1 and si-TRPC3 on the cell viability, cell
      cycle, and the protein expression of p-p38, p-JNK, cleaved caspase-3, and Bcl-2
      in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and
      TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially,
      through regulating Ca2+ influx.

PMID- 29574926
TI  - Recurrent GNA14 mutations in anastomosing haemangiomas.

PMID- 29574925
TI  - Low-density lipoprotein-cholesterol lowering in individuals at intermediate
      cardiovascular risk: Percent reduction or target level?
AB  - BACKGROUND: Recommendations for blood cholesterol management differ across
      different guidelines. HYPOTHESIS: Lipid-lowering strategies based on low-density
      lipoprotein-cholesterol (LDL-c) percent reduction or target concentration may
      have different effects on the expected cardiovascular benefit in intermediate
      risk individuals. METHODS: We selected individuals between 40 and 75 years of age
      with 10-year risk for atherosclerotic cardiovascular disease (ASCVD) between 5.0%
      and <7.5% who underwent a routine health screening. For every subject, we
      simulated a strategy based on a 40% LDL-c reduction (S40% ) and another strategy
      based on achieving LDL-c target <=100 mg/dL (Starget-100 ). The cardiovascular
      benefit was estimated assuming a 22% relative risk reduction in major
      cardiovascular events for each 39 mg/dL of LDL-c lowered. RESULTS: The study
      comprised 1756 individuals (94% men, 52 +/- 5 years old). LDL-c and predicted 10
      year ASCVD risk would be slightly lower in S40% compared to Starget-100 . The
      number needed to treat to prevent 1 major cardiovascular event in 10 years (NNT10
      ) would be 56 with S40% and 66 with Starget-100 . S40% would prevent more events
      in individuals with lower baseline LDL-c, whereas Starget-100 would be more
      protective in those with higher LDL-c. A dual-target strategy (40% minimum LDL-c
      reduction and achievement of LDL-c <=100 mg/dL) would be associated with outcomes
      similar to those expected with the S40% (NNT10 = 55). CONCLUSIONS: In an
      intermediate-risk population, cardiovascular benefit from LDL-c lowering may be
      optimized by tailoring the treatment according to the baseline LDL-c or by
      setting a dual-target strategy (fixed dose statin plus achievement of target LDL
      c concentration).

PMID- 29574927
TI  - Parental posttraumatic stress and child behavioral problems in world trade center
      responders.
AB  - BACKGROUND: We investigated trans-generational associations between Post
      Traumatic Stress Disorder (PTSD) symptoms in World Trade Center (WTC) responders
      and behavioral problems in their children. METHODS: Participants were WTC
      responders-8034 police and 8352 non-traditional (eg, construction workers)-with
      one or more children at the time of their first visit to the World Trade Center
      Health Program (WTC-HP). Self-report questionnaires were administered
      approximately 4 years after the 9/11 WTC attack. RESULTS: A total of 31.4% of non
      traditional and 20.0% of police responders reported behavioral problems in their
      children. Non-traditional responder status, female sex, Hispanic ethnicity, more
      life stressors, more WTC-related PTSD symptoms, and dysphoric arousal symptoms
      were significant correlates of behavioral problems in responders' children.
      CONCLUSIONS: Specific parental sociodemographic, psychosocial and clinical
      characteristics, as well as PTSD symptom severity, were significant correlates of
      child behavior problems. Findings encourage monitoring and early intervention for
      children of disaster responders, particularly those at highest risk.

PMID- 29574928
TI  - Cell type-dependent functions of microRNA-92a.
AB  - The role of miR-17/92 family in development and progression of various cancers
      has been established. The members of this miRNA family have been shown to be over
      expressed and target various genes within proliferation, metastasis and
      angiogenesis pathways. Although all members might be overexpressed in a certain
      cancer type, only certain members of the family may have roles in progression of
      that cancer. In this study, we have chosen miR-92a, a member of the miR-17/92
      family to compare its function in three different cancer cell lines. HL60, MCF7,
      and Jurkat cell lines were transduced with miR-92a and proliferation and
      apoptosis was measured in these cells by cell count, MTT, and caspase assays.
      Although in comparison to pre-miR-17/92, the level of miR-92a is higher in Jurkat
      cells compared to MCF7 and HL60 cells, here we have shown that increasing miR-92a
      levels results in apoptosis in Jurkat cells and proliferation in MCF7 and HL60
      cells. miR-92a was also microinjected into mice fertilized eggs and after
      dissection, apoptosis was only observed in white pulp of spleen that is mainly
      made up of white blood cells. Our results show that miR-92a possesses a cell-type
      dependent function.

PMID- 29574929
TI  - Impact of histological subtype on the prognosis of patients undergoing surgery
      for colon cancer.
AB  - BACKGROUND: The effect of the histological subtype on the prognosis of patients
      undergoing surgery for colon cancer (CC) is not completely understood. METHODS:
      The Surveillance, Epidemiology, and End Results (SEER) 2004-2014 database was
      used to compare the long-term outcomes of patients undergoing colon resection for
      classical adenocarcinoma (CA), mucinous adenocarcinoma (MUC), and signet-cell
      adenocarcinoma (SC). RESULTS: A total of 153 317 (89%) patients had CA, 16 660
      (10%) MUC while 1810 (1%) patients had SC subtype. Patients with MUC and SC more
      frequently had a poorly differentiated CC and were more likely to present with
      advanced disease compared with CA patients (P < 0.001). Patients with CA had a 5
      year OS of 62% versus 55% and 34% for patients with MUC and SC subtypes,
      respectively (P = 0.001). On multivariable analysis, site of cancer, tumor grade,
      and TNM stage were associated with prognosis (all P < 0.001). After controlling
      for these risk factors, patients with MUC (HR, 1.09, P < 0.001) and SC (HR, 1.47,
      P < 0.001) had a roughly 10% and 50% increased hazard of death, respectively,
      compared with CA patients. CONCLUSIONS: MUC and SC are distinct subtypes of CC
      associated with a worse prognosis. These data can help inform discussion about
      prognosis and possibly direct adjuvant management.

PMID- 29574930
TI  - Multicentric cutaneous keratoacanthomas in a free-living marmoset (Callithrix
      sp.).
AB  - Cutaneous neoplasia is common in non-human primates. We describe the gross and
      microscopic features of multicentric cutaneous keratoacanthomas in a free-living
      marmoset (Callithrix sp.). Immunohistochemistry for human papillomavirus and
      herpes simplex virus type I and simplex virus type II was negative.
      Keratoacanthomas should be included in the differential diagnosis for cutaneous
      masses in non-human primates.

PMID- 29574931
TI  - An Emerging Group of Membrane Property Sensors Controls the Physical State of
      Organellar Membranes to Maintain Their Identity.
AB  - The biological membranes of eukaryotic cells harbor sensitive surveillance
      systems to establish, sense, and maintain characteristic physicochemical
      properties that ultimately define organelle identity. They are fundamentally
      important for membrane homeostasis and play active roles in cellular signaling,
      protein sorting, and the formation of vesicular carriers. Here, we compare the
      molecular mechanisms of Mga2 and Ire1, two sensors involved in the regulation of
      fatty acid desaturation and the response to unfolded proteins and lipid bilayer
      stress in order to identify their commonalities and specializations. We will
      speculate on the cellular significance of membrane property sensors in other
      organelles and discuss their putative mechanisms. Based on these findings, we
      propose membrane property sensors as an emerging class of proteins with wide
      implications for organelle communication and function.

PMID- 29574932
TI  - High-Frame Rate Vector Flow Imaging of the Carotid Bifurcation in Healthy Adults:
      Comparison With Color Doppler Imaging.
AB  - OBJECTIVES: To evaluate the carotid bifurcation in healthy adults using a
      commercial system equipped with high-frame rate vector flow imaging (VFI) based
      on the plane wave and to compare VFI with color Doppler imaging. METHODS: Carotid
      bifurcation diameters and flow characteristics of 60 vessels in 60 healthy
      volunteers were evaluated quantitatively and qualitatively to assess complex flow
      patterns and their extension and duration. RESULTS: Complex flow in the internal
      carotid artery (ICA) was associated with a statistically significant difference
      in the DeltaICA sinus-to-common carotid artery (CCA) diameter ratio (the relative
      change in diameter between the CCA and ICA sinus.) Vector flow imaging and color
      Doppler imaging were in accordance when detecting complex flow in 96.7% of cases;
      in 3.3% of cases, only VFI identified small recirculation areas of short
      duration. Vector flow imaging highlighted a larger extension of the complex flow
      (mean +/- SD, 47.7 +/- 28.5 mm2 ; median, 45.5 mm2 ) compared with color Doppler
      imaging (mean, 29.2 +/- 19.9 mm2 ; median, 29.5 mm2 ) and better depicted
      different complex flow patterns; a strong correlation (r = 0.84) was found
      between the DeltaICA sinus-to-CCA diameter ratio and the complex flow extension.
      Vector flow imaging showed a longer duration of the flow disturbances (mean, 380
      +/- 218 milliseconds; median, 352.5 milliseconds) compared with color Doppler
      imaging (mean, 325 +/- 206 milliseconds; median, 333 milliseconds), and there was
      a strong correlation (r = 0.92). CONCLUSIONS: Vector flow imaging is as effective
      as color Doppler imaging in the detection of flow disturbances, but it is more
      powerful in the assessment of complex flow patterns.

PMID- 29574933
TI  - The association of serum FGF23 and non-alcoholic fatty liver disease is
      independent of vitamin D in type 2 diabetes patients.
AB  - Recent studies have shown that circulating fibroblast growth factor (FGF) 23 and
      vitamin D levels are closely correlated with insulin resistance. The aim of this
      study was to investigate the relationship among serum FGF 23 levels, serum 25
      hydroxyvitamin D [25(OH)D] levels, and non-alcoholic fatty liver disease (NAFLD)
      in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331
      hospitalized T2DM patients (209 patients with NAFLD and 122 patients without
      NAFLD). Serum FGF23 levels were measured using a sandwich enzyme-linked
      immunosorbent assay. Serum 25(OH)D levels were determined by an
      electrochemiluminescence immunoassay. NAFLD was diagnosed by hepatic ultrasound,
      and the fatty liver index (FLI) was calculated to quantify hepatic steatosis.
      Results showed that T2DM patients with NAFLD had significantly higher serum FGF23
      levels (44.17 [37.92-51.30] pg/mL vs 40.21 [34.07-48.33] pg/mL, P = .002), but
      lower serum 25(OH)D levels (16.43 [12.70-21.37] ng/mL vs 19.59 [13.78-26.26]
      ng/mL, P = .002) than those without NAFLD. Moreover, the incidence rate of NAFLD
      increased with increasing serum FGF23 levels and decreased with increasing
      25(OH)D levels (both P < .05). Logistic regression analysis showed that both
      serum FGF23 and 25(OH)D levels were independent factors for NAFLD (both P < .05).
      Furthermore, a multiple stepwise regression analysis also revealed that both
      serum FGF23 and 25(OH)D levels were independently correlated with FLI (both P <
      .01). In conclusion, both high FGF23 and low vitamin D levels showed an
      independent relationship with NAFLD in Chinese T2DM patients, indicating that
      FGF23 and vitamin D function via different regulatory pathways in the liver.

PMID- 29574935
TI  - Investigating the role of articulatory organs and perceptual assimilation of
      native and non-native fricative place contrasts.

PMID- 29574934
TI  - The power of precise bioinformatics prediction of miRNA:mRNA interactions:miR
      4699 as a potential inducer of Wnt signaling pathway.
AB  - microRNAs have attracted interest because of their regulatory effects on gene
      expression. Experimental detection of potential targets of miRNAs is a laborious
      task. Considering the expensive techniques of detection, computational approaches
      for miRNA target prediction can be used as the first step in miRNA research. A
      large number of tools and algorithms have been developed during the last two
      decades, led to problems such as confusion in selecting an appropriate tool and
      false positive or negative results. Therefore, one of the most frequent problems
      and critical issues of miRNA research is finding a reliable miRNA target
      prediction tool. In this study, we have proposed a research direction and
      introduced user-friendly and current databases and tools with the highest
      accuracy. To verify whether our proposed research direction is practical, we have
      provided a case example of predicting a miRNA which can target negative
      regulators of osteogenesis and experimentally evaluated the accuracy of the
      prediction results by Real-Time PCR and Luciferase assay. The results of RT-qPCR
      and Luciferase assay indicated a significant decline in expression of Dickkopf
      related protein 1 (DKK1) and tumor necrosis factor ligand superfamily member 11
      (TNFSF11) as the key negative regulators of osteogenesis upon overexpression of
      miR-4699-3p. The results emphasize the validity and importance of accurate in
      silico investigation as the first step in experimental studies. This is the first
      report detailing the prediction and validation of miR-4699-3p target genes. We
      suggest hsa-miR-4699 for further investigation as an osteogenic miRNA for
      therapeutics purposes.

PMID- 29574936
TI  - Analysis of tumoral spheres growing in a multichamber microfluidic device.
AB  - Lab on a Chip (LOC) farming systems have emerged as a powerful tool for single
      cell studies combined with a non-adherent cell culture substrate and single cell
      capture chips for the study of single cell derived tumor spheres. Cancer is
      characterized by its cellular heterogeneity where only a small population of
      cancer stem cells (CSCs) are responsible for tumor metastases and recurrences.
      Thus, the in vitro strategy to the formation of a single cell-derived sphere is
      an attractive alternative to identify CSCs. In this study, we test the
      effectiveness of microdevices for analysis of heterogeneity within CSC
      populations and its interaction with different components of the extracellular
      matrix. CSC could be identify using specific markers related to its pluripotency
      and self-renewal characteristics such as the transcription factor Oct-4 or the
      surface protein CD44. The results confirm the usefulness of LOC as an effective
      method for quantification of CSC, through the formation of spheres under
      conditions of low adhesion or growing on components of the extracellular matrix.
      The device used is also a good alternative for evaluating the individual growth
      of each sphere and further identification of these CSC markers by
      immunofluorescence. In conclusion, LOC devices have not only the already known
      advantages, but they are also a promising tool since they use small amounts of
      reagents and are under specific culture parameters. LOC devices could be
      considered as a novel technology to be used as a complement or replacement of
      traditional studies on culture plates.

PMID- 29574937
TI  - Serologic markers of viral infection and risk of non-Hodgkin lymphoma: A pooled
      study of three prospective cohorts in China and Singapore.
AB  - Incidence rates of non-Hodgkin lymphoma (NHL) and distributions of certain
      viruses differ between East Asian and Western populations. There are limited data
      on associations between serologic markers of multiple viral infections in pre
      diagnostic blood and NHL risk in East Asians. We conducted a nested case-control
      study of 214 NHL cases and 214 matched controls from three population-based
      prospective cohorts in Shanghai and Singapore. Antibodies against antigens from
      herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were
      measured in plasma or serum using fluorescent bead-based multiplex assays.
      Conditional logistic regression was used to evaluate associations between
      antibody levels and NHL risk. An increased risk of NHL was observed for higher
      compared to lower EA-D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) =
      1.10-3.81; ptrend  = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96-4.89; ptrend  =
      0.008) Epstein-Barr Virus (EBV) antibodies, as well as for antibody
      seropositivity against the IE1A human herpesvirus-6 (HHV-6) antigen (OR = 1.85,
      95% CI = 1.04-3.29). An increased NHL risk was also observed for higher compared
      to lower antibodies against the HBV-HBc and HBe antigens. An increased risk of
      NHL in relation to EBV and HBV infection in East Asians is consistent with
      findings in several studies of Western populations, suggesting similar viral risk
      factors for NHL in these diverse populations with distinct patterns of NHL. The
      association between HHV-6 antibodies and NHL has not previously been reported in
      a prospective study in this population and will require replication.

PMID- 29574938
TI  - Resolvin E1 (Rv E1 ) attenuates LPS induced inflammation and subsequent atrophy
      in C2C12 myotubes.
AB  - Resolution of inflammation is now known to be an active process which in part is
      instigated and controlled by specialized pro-resolving lipid mediators (SPM's)
      derived from dietary omega-3 fatty acids. Resolvin E1 (Rv E1 ) is one of these
      SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both
      molecular and phenotypic functional measures we report that in a model of
      Lipopolysaccharide (LPS) induced inflammation, Rv E1 attenuated mRNA levels of
      both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect
      on tumor necrosis factor-alpha or interlukin-1beta in C2C12 skeletal muscle
      myotubes. Findings at the molecular level were transferred into similar changes
      in extracellular protein levels of the corresponding genes with the greatest
      attenuation being noted in IL-6 protein concentrations. Rv E1 instigated
      beneficial morphological changes through the prevention of LPS induced skeletal
      muscle atrophy, in tandem with attenuation of the LPS induced reduction in
      contractile force in tissue engineered skeletal muscle. These findings
      demonstrate, in our model of endotoxin induced inflammation in skeletal muscle,
      that Rv E1 has pro-resolving properties in this cell type. Our data provides
      rationale for further investigation into the mechanistic action of Rv E1 in
      skeletal muscle, with the vision of having potential benefits for the
      prevention/resolution of in-vivo skeletal muscle atrophy.

PMID- 29574939
TI  - Reconstruction of undersampled radial free-breathing 3D abdominal MRI using
      stacked convolutional auto-encoders.
AB  - PURPOSE: Free-breathing three-dimensional (3D) abdominal imaging is a challenging
      task for MRI, as respiratory motion severely degrades image quality. One of the
      most promising self-navigation techniques is the 3D golden-angle radial stack-of
      stars (SOS) sequence, which has advantages in terms of speed, resolution, and
      allowing free breathing. However, streaking artifacts are still clearly observed
      in reconstructed images when undersampling is applied. This work presents a novel
      reconstruction approach based on a stacked convolutional auto-encoder (SCAE)
      network to solve this problem. METHODS: Thirty healthy volunteers participated in
      our experiment. To build the dataset, reference and artifact-affected images were
      reconstructed using 451 golden-angle spokes and the first 20, 40, or 90 golden
      angle spokes corresponding to acceleration rates of 31.4, 15.7, and 6.98,
      respectively. In the training step, we trained the SCAE by feeding it with
      patches from artifact-affected images. The SCAE outputs patches in the
      corresponding reference images. In the testing step, we applied the trained SCAE
      to map each input artifact-affected patch to the corresponding reference image
      patch. RESULT: The SCAE-based reconstruction images with acceleration rates of
      6.98 and 15.7 show nearly similar quality as the reference images. Additionally,
      the calculation time is below 1 s. Moreover, the proposed approach preserves
      important features, such as lesions not presented in the training set.
      CONCLUSION: The preliminary results demonstrate the feasibility of the proposed
      SCAE-based strategy for correcting the streaking artifacts of undersampled free
      breathing 3D abdominal MRI with a negligible reconstruction time.

PMID- 29574940
TI  - Prenatal diagnosis of a fetus with Proteus syndrome.

PMID- 29574941
TI  - A systematic review and meta-analysis of randomized controlled trials: Skin-patch
      of Chinese herbal medicine for patients with acute gouty arthritis.
AB  - AIMS: To evaluate the evidence of the effectiveness and safety of Chinese herbal
      medicine skin-patches for patients with acute gouty arthritis. BACKGROUND: Acute
      gouty arthritis is a problem that can limit the level of activity and impair the
      quality of life. In China, many clinical studies have demonstrated that skin
      patches of Chinese herbal medicines benefit patients with acute gouty arthritis.
      However, the reported clinical effects vary. DESIGN: A systematic review and meta
      analysis of randomized controlled trials. DATA SOURCES: Three English databases
      including CENTRAL (1993 to February 2017), PubMed (1966 to February 2017) and
      EMBASE (1974 to February 2017) and four Chinese databases including Chinese
      National Knowledge Infrastructure, Chinese VIP Information, SinoMed and Wanfang
      (all, 1949 - February 2017) were searched. Randomized controlled trials that
      compared skin-patches of Chinese herbal medicine with or without conventional
      treatments to conventional treatments, no treatment or a placebo treatment for
      patients with acute gouty arthritis were included. REVIEW METHODS: We conducted a
      systematic review and meta-analysis following the Cochrane process. Two authors
      selected the studies, extracted the data and evaluated the risk of bias of the
      included trials. RESULTS: Nineteen studies met our inclusion criteria. After
      synthesizing the data, the results showed that skin-patches of CHM combined with
      Western medicine seemed to be more effective than Western medicine alone for pain
      relief in patients with acute gouty arthritis and had fewer adverse events.
      CONCLUSION: Due to the quality of the data, larger and more rigorously designed
      clinical trials with proper outcome measures are necessary.

PMID- 29574942
TI  - The contribution of occupation to children's experience of resilience: A
      qualitative descriptive study.
AB  - BACKGROUND: This qualitative descriptive study explored what occupations children
      aged 10-13 years participate in and how participation in occupation contributes
      to resilience from their perspective. Little is known about how occupations
      contribute to resilience, and less is known from children's perspectives.
      Exploring how participation in occupation contributes to resilience is important
      as children continue to face adverse situations; resilience may help protect
      their development against uncertainty. METHODS: Following ethics approval eight
      participants were recruited through schools in a large New Zealand city. Data
      were collected through semi-structured interviews and one focus group, these were
      audio recorded and transcribed. The six-phase process of thematic analysis,
      developed by Braun and Clarke (), was utilised to analyse the data. FINDINGS:
      Three main themes emerged from the data: what resilience is, occupations children
      do and how those occupations contribute to resilience and thirdly; building
      participation and resilience. The study revealed sophisticated descriptions of
      what resilience meant to the participants from their experience, which included
      the ideas of bouncing back and staying strong. The participants described what
      occupations they participate in and how these occupations connect to resilience.
      The participants also described their experience of how participation in their
      occupations helped build resilience by fostering support, letting go,
      experiencing distraction, and experiencing fun and happiness. CONCLUSION: The
      findings suggest that health professionals, policy makers and educators have much
      to learn from children. Specifically, the need for children to participate in
      occupations as a way to build resilience. This indicates that a child-focussed
      approach is needed to incorporate children's perspectives in practice and policy
      development. The findings suggest that practitioners working with children should
      incorporate participation in occupation in social, health and education
      intervention plans with children, as well as use occupation based coping
      strategies when teaching children skills to manage challenges in life.

PMID- 29574943
TI  - Celebrating diversity to promote and create inclusive curricula.

PMID- 29574944
TI  - Brain-themed self-help and the healthcare provider in the United States.
AB  - People commonly use the Internet to search for health information and tend to use
      the information they find without regard to source or credibility. Although
      regulation plays some role in minimizing false claims made by manufacturers of
      self-help products, effective communication with health professionals likely
      offers greater protection to the patient or consumer accessing self-help
      materials. In order to best serve patients (or healthcare consumers), providers
      should educate them about their healthcare needs, inquire about self-help product
      use, understand appropriate use, discuss the risks and benefits of use, monitor
      the patients' condition during use, and document these conversations. Although
      some people fear that patient use of brain-themed self-help will undermine the
      doctor-patient relationship, it is more likely to open another avenue of
      communication if providers are knowledgeable about self-help products. Given the
      rise in importance of the Internet as a source of information for people, opting
      out of these discussions is realistically not an option.

PMID- 29574945
TI  - Exogenous Cushing syndrome from an unexpected source of systemic steroids.
AB  - A 12-year-old Hispanic boy with chronic atopic dermatitis and cushingoid features
      presented to our institution. He was being treated with an unknown quantity of
      oral prednisolone 15 mg/5 mL, equivalent to 70 mg/m2 /d of oral prednisone,
      purchased over the counter in El Salvador. Systemic corticosteroids are not
      recommended for chronic therapy of atopic dermatitis because of their significant
      adverse effects. Foreign-sourced pharmaceuticals account for almost half of the
      drugs consumed in the United States, which means that, to protect our patients,
      medical providers must inquire about and report unsafe medications deemed legal
      outside the United States to the Food and Drug Administration.

PMID- 29574946
TI  - Cyclic AMP and glycogen synthase kinase 3 form a regulatory loop in spermatozoa.
AB  - The multifaceted glycogen synthase kinase (GSK3) has an essential role in sperm
      and male fertility. Since cyclic AMP (cAMP) plays an important role in sperm
      function, we investigated whether GSK3 and cAMP pathways may be interrelated. We
      used GSK3 and soluble adenylyl cyclase (sAC) knockout mice and pharmacological
      modulators to examine this relationship. Intracellular cAMP levels were found to
      be significantly lower in sperm lacking GSK3alpha or GSK3beta. A similar outcome
      was observed when sperm cells were treated with SB216763, a GSK3 inhibitor. This
      reduction of cAMP levels was not due to an effect on sperm adenylyl cyclase but
      was caused by elevated phosphodiesterase (PDE) activity. The PDE4 inhibitor
      RS25344 or the general PDE inhibitor IBMX could restore cAMP levels in sperm
      lacking GSK3alpha or beta-isoform. PDE activity assay also showed that
      hyperactivated PDE4 contributes in lowering of cAMP levels in GSK3alpha null
      sperm suggesting that in wild-type sperm PDE4 activity is kept in check by GSK3.
      Conversely, PKA being triggered by cAMP, affected GSK3 activity through
      increasing its phosphorylation. Increased GSK3 phosphorylation also occurred by
      inhibition of sperm specific protein phosphatase type 1, PP1gamma2. The
      relationship between cAMP, GSK3, and PP1gamma2 activities was also confirmed in
      sperm from sAC null mice. Pull-down assay using recombinant PP1gamma2 indicated
      that PKA, GSK3, and PP1gamma2 could exist as a complex. Pharmacological
      inhibition of GSK3 in mature spermatozoa resulted in significantly reduced
      fertilization of eggs in vitro. Our results show that cAMP, PKA, and GSK3 are
      interrelated in regulation of sperm function.

PMID- 29574947
TI  - Corrigendum.

PMID- 29574948
TI  - Editorial: Beyond behavior? Institutions, interactions and inequalities in the
      response to antimicrobial resistance.

PMID- 29574949
TI  - Biological effects of interleukin-6 on Gingival Fibroblasts: Cytokine regulation
      in periodontitis.
AB  - Periodontitis is a bacterial infectious disease, and many inflammatory cytokines
      regulate periodontitis pathophysiology through a crosstalk between tissue cells
      and immune cells. Interleukin (IL)-6 is an important cytokine involved in the
      regulation of host response to bacterial infection. Human Gingival Fibroblasts
      (HGFs) are the most abundant cells in gingival connective tissues. Various HGF
      responses to periodontal pathogens or inflammatory cytokines contribute to the
      development of periodontitis. Lipopolysaccharide derived from Porphyromonas
      gingivalis (Pg LPS) and IL-1beta significantly increase IL-6 production in HGFs.
      However, IL-6 cannot function in HGFs without the soluble form of the IL-6
      receptor (sIL-6R), because HGFs do not express sufficient cell surface IL-6R to
      bind appreciable levels of IL-6. Importantly, sIL-6R is essential for IL-6
      signaling in HGFs, and the sIL-6R is produced by differentiated THP-1 cells
      treated with IL-6. Calprotectin, a heterodimer of S100A8 and S100A9, is released
      during inflammation and significantly induces IL-6 production in HGFs via toll
      like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappaB) signals. Calprotectin
      also induces sIL-6R production in differentiated THP-1 cells. IL-6 induces
      vascular endothelial growth factor (VEGF), matrix-metalloproteinase-1 (MMP-1),
      and cathepsin L production in HGFs in the presence of sIL-6R. Taken together,
      calprotectin-induced IL-6 production in HGFs may cause periodontitis progression
      through a crosstalk of fibroblasts and macrophages. There are many reports that
      examine how cytokines are released from HGFs to cause beneficial or harmful
      effects in inflamed periodontal lesions. This review explores the pathophysiology
      of periodontitis by focusing IL-6-mediated crosstalk of HGFs and macrophages.

PMID- 29574950
TI  - Automated RBC exchange compared to manual exchange transfusion for children with
      sickle cell disease is cost-effective and reduces iron overload.
AB  - BACKGROUND: Chronic transfusion in sickle cell disease (SCD) remains the gold
      standard therapy for stroke prevention and for patients with severe disease
      despite adequate hydroxyurea treatment. The aim of our study was to assess the
      safety and efficacy of automated red blood cell exchange (aRBX) in patients with
      SCD previously treated with manual exchange transfusion (MET). Costs related to
      transfusion and chelation overtime were evaluated. STUDY DESIGN AND METHODS:
      Beginning in January 2012, children with SCD who weighed 30 kg or more on MET
      could switch to aRBX. Clinical, biological, and procedures' data, including
      costs, were recorded for the last 6 months on MET and compared to those after the
      first and the second year on aRBX. RESULTS: Ten patients switched from MET to
      aRBX at a median age of 11.8 years. After the switch, median hemoglobin S (HbS)
      increased significantly (33.5% on MET compared to 45% on aRBX; p < 0.001) but
      remained in the target values for all patients. Median ferritin decreased
      significantly (663.3 ug/L on MET compared to 126.8 ug/L on aRBX; p < 0.001) and
      intervals between procedures were significantly longer. The requirements of red
      blood cells (RBCs)/kg/year were not different on MET (0.88 unit/kg/year) than
      during the second year on aRBX (1.07 unit/kg/year; p = NS). MET costs were
      similar compared to aRBX since chelation was stopped in previously treated
      patients. CONCLUSION: Erythrocytapheresis reduces iron overload and allows a
      longer interval between procedures without a higher RBC requirement from the
      second year on aRBX. The cost did not increase as estimated in our Belgian Health
      Care System.

PMID- 29574951
TI  - In vitro water resistance testing using SPF simulation based on spectroscopic
      analysis of rinsed sunscreens.
AB  - OBJECTIVE: Water resistance retention (WRR) is the third performance attribute of
      sunscreens. Today, the standardized method for testing WRR is performed in vivo.
      For screening purposes, an in vitro method is highly preferable. Up to now,
      however, available methods have failed in accurately predicting in vivo WRR. In
      this study, we examine a novel in vitro approach aimed at enhancing in vivo
      prediction of WRR. METHODS: We investigated two approaches, including a
      traditional procedure referred to as the 'plate method', which involves measuring
      in vitro sun-protection factor (SPF) before and after water immersion, and a new
      approach termed the 'solution method'. The latter employed a computational method
      to calculate the SPF using UV transmittance measurements of a sunscreen solution,
      obtained by rinsing the substrate without water immersion and with water
      immersion. It also had a model function for describing film irregularity. The aim
      was to avoid the effect of substrate-to-product affinity on the film
      distribution, which impacts the measured absolute value of the in vitro SPF
      occurring in the conventional approach. For both methodologies, we assessed two
      substrates for the sunscreen application based on different polymers, the widely
      used polymethylmethacrylate (PMMA) and the ethylene methacrylate acid copolymer
      (EMA). RESULTS: The agreement between in vivo and in vitro WRR values obtained
      from each of the four test conditions was analysed using different sunscreens. No
      correlation was found between in vivo and in vitro WRR using the plate method,
      independently of the plate type. In contrast, the solution method, using EMA
      plates, revealed a significant correlation between in vivo and in vitro results,
      with an especially high correlation for in vivo non-water-resistant sunscreens.
      The results of two operators were comparable. The solution method was unsuitable
      for PMMA plates. CONCLUSION: Despite the small discrepancy remaining between WRR
      values obtained from the in vitro solution method and in vivo method, which
      itself shows variability in results, this work provided a new insight into the in
      vitro testing of water resistance of sunscreens.

PMID- 29574952
TI  - Introduction to biomedical optical imaging issue.

PMID- 29574953
TI  - News & Announcements: American Society for Laser Medicine and Surgery, Inc.

PMID- 29574954
TI  - Clinical and laboratory factors contributing to uninterpretable beryllium
      lymphocyte proliferation tests (BeLPT).
AB  - BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT), has become the
      principal clinical test for detecting beryllium sensitization and chronic
      beryllium disease. Uninterpretable BeLPT results can occur in a small but
      significant proportion of tests from poor lymphocyte growth (PG) or over
      proliferation of lymphocytes (OP). The clinical and laboratory causes of
      uninterpretable results are not known. METHODS: BeLPT data from the US Department
      of Energy-supported Former Worker Screening Program were analyzed for a 10-year
      period. Drivers of uninterpretable BeLPTs were investigated using multivariable
      models and classification techniques. RESULTS: Three participant attributes were
      significantly associated with PG, while OP showed no significant associations.
      Serum lot for the lymphocyte growth medium accounted for 21% of the variation in
      PG and 16% in OP. CONCLUSION: Serum lots influence the likelihood of having
      uninterpretable BeLPT. To better understand uninterpretable results and possibly
      reduce their occurrence, additional laboratory-related factors should be
      addressed.

PMID- 29574955
TI  - Hepatology Highlights.

PMID- 29574956
TI  - Change in empathy in medical school.

PMID- 29574958
TI  - Physicians actively engaging in seeking feedback for learning through patient
      outcomes.

PMID- 29574959
TI  - Discrimination, harassment and non-reporting in UK medical education.
AB  - CONTEXT: Discrimination and harassment create a hostile environment with
      deleterious effects on student well-being and education. In this study, we aimed
      to: (i) measure prevalences and types of discrimination and harassment in one UK
      medical school, and (ii) understand how and why students report them. METHODS:
      The study used a mixed-methods design. A medical school population survey of 1318
      students was carried out in March 2014. Students were asked whether they had
      experienced, witnessed or reported discrimination or harassment and were given
      space for free-text comments. Two focus group sessions were conducted to elicit
      information on types of harassment and the factors that influenced reporting.
      Proportions were analysed using the Wilson score method and associations tested
      using chi-squared and regression analyses. Qualitative data were subjected to
      framework analysis. Degrees of convergence between data were analysed. RESULTS: A
      total of 259 (19.7%) students responded to the survey. Most participants had
      experienced (63.3%, 95% confidence interval [CI]: 57.3-69.0) or witnessed (56.4%,
      95% CI: 50.3-62.3) at least one type of discrimination or harassment.
      Stereotyping was the form most commonly witnessed (43.2%, 95% CI: 37.4-49.3). In
      the qualitative data, reports of inappropriate joking and invasion of personal
      space were common. Black and minority ethnic students had witnessed and religious
      students had experienced a greater lack of provision (chi2  = 4.73, p = 0.03 and
      chi2  = 4.38, p = 0.04, respectively). Non-heterosexual students had experienced
      greater joking (chi2  = 3.99, p = 0.04). Students with disabilities had
      experienced more stereotyping (chi2  = 13.5, p < 0.01). Female students and
      students in clinical years had 2.6 (95% CI: 1.3-5.3) and 3.6 (95% CI: 1.9-7.0)
      greater odds, respectively, of experiencing or witnessing any type of
      discrimination or harassment. Seven of 140 survey respondents had reported
      incidents (5.0%, 95% CI: 2.4-10.0). Reporting was perceived as ineffective and as
      potentially victimising of the reporter. CONCLUSIONS: Harassment and
      discrimination are prevalent in this sample and associated with gender,
      ethnicity, sexuality, disability and year group. Reporting is rare and perceived
      as ineffective. These findings have informed local developments, future
      strategies and the development of a national prevention policy.

PMID- 29574960
TI  - It's happening sooner than you think: spotlighting the pre-medical realm.

PMID- 29574961
TI  - What else is happening? A more holistic view of programme evaluation.

PMID- 29574962
TI  - Predictive utility cannot substitute for construct validity.

PMID- 29574963
TI  - Conceptualising discrimination in medical education: the hierarchy, the power.

PMID- 29574964
TI  - Frequency of awake bruxism behaviours in the natural environment. A 7-day,
      multiple-point observation of real-time report in healthy young adults.
AB  - The aim of this study was to assess awake bruxism (AB) behaviours in a sample of
      healthy young adults using a smartphone-based application for a real-time report
      (ie, ecological momentary assessment [EMA], also called experience sampling
      method [ESM]). Forty-six dental students used a smartphone application that sent
      15 alerts at random intervals during the day for 1 week to collect AB self
      reports. They had to answer on time by tapping on the display icon that refers to
      their current condition of jaw muscles: relaxed; teeth contact; teeth clenching;
      teeth grinding; jaw clenching without teeth contact (ie, bracing). The average
      frequency of relaxed jaw muscles, as a percentage of answers over the 7 days, was
      71.7%. Teeth contact (14.5%) and jaw clenching (10.0%) were the most frequent AB
      behaviours. No significant gender differences were detected. Interindividual
      differences were quite relevant, but the overall frequency was in general only
      moderately variable from day-to-day. Coefficient of variation (CV) was low for
      the condition "relaxed jaw muscles" (0.44). At the individual level, teeth
      contact was the most prevalent behaviour, with a 39.1%-52.2% proportion of
      subjects reporting it at least once a day. During a 7-day observation period, the
      frequency of real-time report of AB behaviours in a sample of healthy young
      adults was 28.3%. The low daily variability in the average frequency value for
      the relaxed jaw muscles condition suggests that EMA may be a reliable strategy to
      get deeper into the epidemiology of oral behaviours. This investigation
      introduced EMA principles to the study of AB and provided data on the frequency
      of AB behaviours in young adults that could be compared to populations with
      risk/associated factors and possible clinical consequences.

PMID- 29574965
TI  - Predicting Suicide Attempts for Racial and Ethnic Groups of Patients During
      Routine Clinical Care.
AB  - The aim of this study was to examine variation in suicide ideation and its
      relationship to risk of suicide attempt in the subsequent 90 days by race and
      ethnicity. Participants were adults who completed the Patient Health
      Questionnaire depression module (PHQ9) during an outpatient encounter between
      January 10, 2010, and December 12, 2012 (N = 509,945 patients; N = 1,228,308
      completed PHQ9). Data came from the Virtual Data Warehouse from four health care
      systems in the Mental Health Research Network. The sample was majority female
      (73.7%), primarily 30-64 years old (60.1%), healthy (64.5% comorbidity index =
      0), and over half were non-Hispanic White (52.9%). Only Asian patients (OR: 1.31;
      95% CI: 1.24, 1.39) had higher odds of reporting suicide ideation when compared
      to non-Hispanic White people. All racial and ethnic groups had increased risk for
      suicide attempt with increased frequency of suicide ideation. The PHQ9 item 9 can
      be used as an indicator of suicide ideation and risk for suicide attempt up to 90
      days after the reported ideation in racial and ethnic minority patients during
      routine clinical care.

PMID- 29574966
TI  - Burnlike scars: A sign suggestive of KLHL24-related epidermolysis bullosa
      simplex.
AB  - Epidermolysis bullosa simplex is a group of inherited disorders with allelic and
      locus heterogeneity in which skin fragility and blistering within the skin occur.
      Mutations in KRT5 and KRT14 underlie the majority of reported cases. Mutations in
      KLHL24, a gene that encodes KLHL24 protein, have been reported recently to cause
      a generalized subtype of epidermolysis bullosa simplex, presumably by increasing
      the degradation of keratin 14. We describe a case of KLHL24-related epidermolysis
      bullosa simplex and highlight the burn-like pattern of scars.

PMID- 29574967
TI  - Is the incidence of advanced-stage breast cancer affected by whether women attend
      a steady-state screening program?
AB  - In this cross-sectional population-based study, we assessed the incidence of
      advanced breast cancer based on screening attendance. Women from the Netherlands
      Cancer Registry were included if aged >=49 years and diagnosed with breast cancer
      between 2006 and 2011, and data were linked with the screening program. Cancers
      were defined as screen-related (diagnosed <24 months after screening) or
      nonscreened (all other breast cancers). Two cut-offs were used to define advanced
      breast cancer: TNM-stage (III-IV vs 0-I-II) and T-stage alone (>=15 mm vs <15 mm
      or DCIS). The incidence rates were adjusted for age and logistic regression was
      used to compare groups. Of the 72,612 included women diagnosed with breast
      cancer, 44,246 (61%) had screen-related breast cancer. By TNM stage, advanced
      cancer was almost three times as likely to be at an advanced TNM stage in the
      nonscreened group compared with the screen-related group (38 and 94 per 100,000,
      respectively; OR: 2.86, 95%CI: 2.72-3.00). By T-stage, the incidence of advanced
      cancer was higher overall, and in nonscreened women was significantly higher than
      in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78-1.93). Data on
      actual screening attendance showed that the incidence of advanced breast cancer
      was significantly higher in nonscreened women than in screened women, supporting
      the expectation that screening would cause a stage shift to early detection.
      Despite critical evaluations of breast cancer screening programs, our data show
      that breast cancer screening is a valuable tool that can reduce the disease
      burden in women.

PMID- 29574968
TI  - Predictors of childhood trajectories of overt and indirect aggression: An
      interdisciplinary approach.
AB  - The aim of this study was to advance our understanding of the development of
      aggression in boys and girls by testing a model combining insights from both
      evolutionary theory and developmental psychology. A sample of 744 children (348
      girls) between six and 13 years old was recruited in schools with high
      deprivation indices. Half of the sample (N = 372; 40.1% girls) had received
      special educational services for behavioral and/or socio-emotional problems. Two
      trajectories for overt aggression and two trajectories for indirect aggression
      were identified and binomial logistic regressions were used to identify
      environmental predictors and sex-specific patterns of these trajectories. Results
      indicated that peer rejection predicted overt aggression and indirect aggression
      and that extraversion and male sex predicted overt aggression. The results also
      showed that interaction between parental practices and some child temperament
      traits predicted overt aggression (coercion and lack of supervision associated
      with extraversion or low effortful control) or indirect aggression (coercion and
      neglect associated with negative affect or low effortful control), and the
      absence of a father figure predicted high indirect aggression in girls.

PMID- 29574969
TI  - Neutrophilic urticarial dermatosis as a presenting feature of systemic juvenile
      idiopathic arthritis.
AB  - This report describes a case of chronic neutrophilic urticarial dermatosis as a
      presenting feature of systemic juvenile idiopathic arthritis. When encountered in
      children, neutrophilic urticarial dermatosis should raise suspicion of autoimmune
      or autoinflammatory disease.

PMID- 29574970
TI  - Migration Study of Butylated Hydroxytoluene and Irganox 1010 from Polypropylene
      Treated with Severe Processing Conditions.
AB  - : Safety concerns have emerged over the increased use of polypropylene (PP) in
      food-packaging markets. Some antioxidants in PP can migrate to foods and cause
      undesirable effects in humans. In this study, migration behaviors of butylated
      hydroxytoluene (BHT) and Irganox 1010 (I-1010) in PP sheets were determined
      according to the US FDA migration test conditions. In particular, we tested the
      effects of severe conditions of food processing and storage, such as autoclave
      heating (sterilization at about 121  degrees C), microwave radiation (700 W), and
      deep freezing (-30  degrees C) on migration of antioxidants. Migrant
      concentrations were higher in 95% ethanol as lipid food simulant, because of the
      hydrophobic nature of both PP and antioxidants. Autoclave heating treatment
      increased migrant concentrations compared with other processing conditions.
      Moreover, increased migrant concentrations by deep freezing condition were
      attributed to the brittleness of PP at freezing temperature. Regardless of
      processing conditions, BHT which has a lower molecular weight, migrated faster
      than I-1010. PRACTICAL APPLICATION: The antioxidants with hydrophobic nature such
      as butylated hydroxytoluene (BHT) and Irganox 1010 (I-1010) in polypropylene
      sheets would be migrated to foods, which is an important issue for industrial
      production food packaging materials. Migration behavior was promoted by severe
      processing conditions such as autoclave heating, microwave radiation, freezing,
      and especially autoclave heating treatment led the highest migration among them.
      Therefore, control of chemical additive migration from polypropylene food
      packaging is needed for safe food processing.

PMID- 29574971
TI  - Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for
      which there is no effective therapy. Interest has grown in developing treatments
      for this condition, with several agents proposed as potential therapies. However,
      there is a lack of clarity about how to measure clinical benefit in trials
      involving patients with this complex and rare disease. This article reviews
      regulatory information, the available literature on natural history, as well as
      potential candidate clinical and surrogate endpoints for PSC. (Hepatology 2018;
      00:000-000).

PMID- 29574972
TI  - Development of a new patient-reported outcome (PRO) measure on the Impact of
      Nighttime Urination (INTU) in patients with nocturia-Psychometric validation.
AB  - AIMS: To psychometrically evaluate the Impact of Nighttime Urination (INTU)
      questionnaire, a new patient-reported outcome measure developed to assess the
      impact of nocturia on health and functioning in a multicenter, behavioral
      modification (fluid restriction) study. METHODS: Participants aged 50-95 years
      with at least two voiding episodes/night for >=6 months completed voiding diaries
      and the INTU on 3 consecutive days during weeks 1 and 2 (same day recall) and
      completed the Pittsburgh Sleep Quality Index (PSQI) and Nocturia Quality of Life
      Questionnaire (N-QOL) at baseline and days 8 and 15. Psychometric evaluations of
      the INTU were conducted. RESULTS: Rasch analysis showed the INTU to be a
      unidimensional construct, with most items located on the severe end of the
      symptom severity continuum. In addition to an Overall Impact Score (10 items),
      exploratory factor analysis affirmed by confirmatory factor analysis identified
      two domains: Daytime (six items) and Nighttime (four items) Impact Scores
      (comparative fit index = 0.968; root mean square error of approximation = 0.08).
      Concurrent validity met prespecified hypotheses, indicating similarity of
      concepts with the PSQI (correlation [r] = 0.627) and N-QOL (r = -0.784) total
      scores. The INTU differentiated among patients with different nocturic episode
      frequencies (P < 0.05 for all three summary scores). Statistically significant
      decreases were observed in mean Overall and Nighttime Impact Scores at week 2
      versus week 1 in responders, indicating that the instrument can detect changes in
      response to symptom improvements. CONCLUSIONS: The INTU questionnaire
      demonstrated robust measurement properties and is a suitable tool for assessing
      the patient-reported impact of nocturia on health and functioning.

PMID- 29574973
TI  - Adenosine-loaded dissolving microneedle patches to improve skin wrinkles, dermal
      density, elasticity and hydration.
AB  - OBJECTIVE: Although dissolving microneedle patches have been widely studied in
      the cosmetics field, no comparisons have been drawn with the topical applications
      available for routine use. In this study, two wrinkle-improving products,
      adenosine-loaded dissolving microneedle patches and an adenosine cream, were
      evaluated for efficacy, with respect to skin wrinkling, dermal density,
      elasticity, and hydration, and safety in a clinical test on the crow's feet area.
      METHODS: Clinical efficacy and safety tests were performed for 10 weeks on 22
      female subjects with wrinkles around their eyes. The adenosine-loaded dissolving
      microneedle patch was applied once every 3 days, in the evening, for 8 weeks to
      the designated crow's feet area. The adenosine cream was applied two times per
      day, in the morning and evening, for 8 weeks to the other crow's feet area. Skin
      wrinkling, dermal density, elasticity, and hydration were measured by using
      PRIMOS(r) premium, Dermascan(r) C, Cutometer(r) MPA580, and Corneometer(r) CM
      825, respectively. In addition, subjective skin irritation was evaluated by self
      observation, and objective skin irritation was assessed through expert
      interviews. RESULTS: The adenosine-loaded dissolving microneedle patches had a
      similar or better efficacy than the adenosine cream. Both groups showed
      statistically significant efficacy for almost all parameters (P < 0.05). The
      dissolving microneedle patches had a long-lasting effect on the average wrinkle
      depth (P < 0.05), only showed efficacy in dermal density (P < 0.05), had an early
      improving effect on elasticity (P < 0.05), and demonstrated better hydration
      efficacy (P < 0.001). No adverse effects were observed in either group during the
      test period. CONCLUSIONS: In the clinical efficacy test of four skin-improvement
      parameters, adenosine-loaded dissolving microneedle patches showed the same or
      better effect than the adenosine cream, although the weekly adenosine dose was
      140 times lower. The dissolving microneedle patches caused no adverse reactions.
      These adenosine-loaded dissolving microneedle patches are expected to be safe,
      effective, and novel cosmetics for skin improvement.

PMID- 29574974
TI  - A pharmacological rationale for improved everolimus dosing in oncology and
      transplant patients.
AB  - AIMS: Everolimus is a drug from the class of mammalian target of rapamycin
      inhibitors used for both immunosuppressant and oncological indications. We
      postulate that there is room for improvement of dosing, as the optimal
      immunosuppressive dose in calcineurin-free regimens is unknown and since the once
      daily dosing regimen for oncological indications is often associated with
      treatment-limiting toxicity. METHODS: We developed a mechanistic population
      pharmacokinetic model for everolimus in cancer and transplant patients and
      explored alternative dosing regimens. RESULTS: We found that formulation did not
      influence bioavailability and that use of >20 mg prednisolone daily increased
      everolimus clearance. In transplant patients, the approved dose of 0.75-1 mg
      twice daily (BID) results in subtherapeutic trough levels (<6 MUg l-1 ) and that
      a higher starting dose of 2.25-3 mg BID is required. CONCLUSION: For oncological
      indications, our results encourage the investigation of dosing everolimus 3.75 mg
      BID in terms of superiority in safety and noninferiority in efficacy.

PMID- 29574975
TI  - LncRNA FLVCR1-AS1 acts as miR-513c sponge to modulate cancer cell proliferation,
      migration, and invasion in hepatocellular carcinoma.
AB  - In the present study, we aimed to search for dysregulated lnRNAs in
      Hepatocellular carcinoma (HCC) tissues, and analyze the relationship of its
      expression level with the clinicopathological feature and patient prognosis. The
      biological function of FLVCR1-AS1, the identified lncRNA, in the process of HCC
      development, and progression was investigated in vitro and in vivo. The
      underlying molecular mechanism was further explored. We determined FLVCR1-AS1
      expression in HCC tissues and peri-tumor tissues by bioinformatic analysis, qRT
      PCR, Northern blot and in situ hybridization. The relationship between FLVCR1-AS1
      expression level and prognosis was determined by analyzing clinical samples. The
      effects of FLVCR1-AS1 knockdown on HCC cell proliferation, apoptosis, migration,
      and invasion were investigated by CCK8, FACS, and tanswell assay, respectively.
      Tumor xenograft model was used to determine the influence of down-regulated
      FLVCR1-AS1 on tumor growth and metastasis. lncRNA FLVCR1-AS1 was extremely up
      regulated in HCC tissues and cell lines. FLVCR1-AS1 expression level was
      positively correlated with tumor severity. FLVCR1-AS1 knockdown remarkably
      inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo
      while induced cell apoptosis. In mechanism, FLVCR1-AS1 acted as a competitive
      endogenous RNAs to sponge miR-513c which targeted the mRNA of MET for
      degradation. By directly sponging miR-513c, FLVCR1-AS1 increased MET expression
      in HCC, and then promoted HCC progression. It was demonstrated that FLVCR1-AS1
      played a positive role in HCC development and progression according to the study
      in its mechanism, function and clinical manifestation, so that it could be
      expected to become a new target in HCC prevention and treatment.

PMID- 29574977
TI  - A systematic review and meta-analysis: Effectiveness of internet empowerment
      based self-management interventions on adults with metabolic diseases.
AB  - AIM: To synthesize the effects of Internet empowerment-based self-management
      interventions on adults with metabolic diseases. BACKGROUND: Metabolic diseases
      are prevalent and burden healthcare systems; they have become a major health
      problem worldwide. The effects of IESMIs on lifestyle changes have been shown to
      improve adults' physiological and psychological conditions. However, we found no
      systematic review evaluating these effects. DESIGN: Systematic review and meta
      analysis of randomized and non-randomized controlled trials, conducted according
      to the Cochrane handbook. DATA RESOURCES: A literature search was conducted using
      the Airiti Library, Association for Computing Machinery, CINAHL, Cochrane
      Library, Embase, ProQuest, PubMed/MEDLINE and Index of the Taiwan Periodical
      Literature System databases (earliest-June 2016). REVIEW METHODS: Two reviewers
      used the Cochrane Collaboration bias assessment tool to assess the methodological
      quality of included studies. Extracted data were entered and analysed using
      RevMan 5.3.5 software. Inverse variance was used to estimate effect sizes.
      Weighted and standardized mean differences with 95% confidence intervals were
      calculated using a random effects model. Subgroup and sensitivity analyses were
      performed. RESULTS: Twenty-one randomized controlled trials were reviewed. Meta
      analysis showed that the intervention significantly improved adults' exercise
      habits, glycated haemoglobin (HbA1c) levels, body weight, empowerment levels and
      quality of life. CONCLUSION: The intervention significantly improve the health
      status of adults with metabolic diseases, in particular their exercise habits,
      HbA1c levels, body weight, empowerment and quality of life. The intervention
      provides more convenient and faster access to healthcare for busy individuals
      with time constraints. These results suggest that healthcare professionals could
      develop accessible and friendly interactive online interfaces for patients to
      expand the use of these interventions in the clinical setting.

PMID- 29574976
TI  - Database for High Throughput Screening Hits (dHITS): a simple tool to retrieve
      gene specific phenotypes from systematic screens done in yeast.
AB  - In the last decade several collections of Saccharomyces cerevisiae yeast strains
      have been created. In these collections every gene is modified in a similar
      manner such as by a deletion or the addition of a protein tag. Such libraries
      have enabled a diversity of systematic screens, giving rise to large amounts of
      information regarding gene functions. However, often papers describing such
      screens focus on a single gene or a small set of genes and all other loci
      affecting the phenotype of choice ('hits') are only mentioned in tables that are
      provided as supplementary material and are often hard to retrieve or search. To
      help unify and make such data accessible, we have created a Database of High
      Throughput Screening Hits (dHITS). The dHITS database enables information to be
      obtained about screens in which genes of interest were found as well as the other
      genes that came up in that screen - all in a readily accessible and downloadable
      format. The ability to query large lists of genes at the same time provides a
      platform to easily analyse hits obtained from transcriptional analyses or other
      screens. We hope that this platform will serve as a tool to facilitate
      investigation of protein functions to the yeast community.

PMID- 29574978
TI  - Canine total hip replacement using a cementless threaded cup and stem: a review
      of 55 cases.
AB  - OBJECTIVES: To determine the long-term results and complications associated with
      the Helica(r) cementless hip endoprosthesis system. MATERIALS AND METHODS:
      Retrospective study of 55 consecutive Helica total hip replacements performed
      between January 2010 and February 2015. RESULTS: A total of 55 total hip
      replacements were performed in 50 dogs; 45 dogs had unilateral hip replacements,
      and five had staged bilateral replacements. A total of 23 first-generation short
      femoral stems were implanted in 22 dogs, of which nine cases (39%) experienced
      complications and 19 (86%) recovered satisfactorily when revisions were included;
      31 second-generation femoral stems were implanted in 28 dogs, of which 10 cases
      (32%) experienced complications, and 26 (93%) made satisfactory recoveries,
      including revisions. In 36 dogs for which data were available, postoperative
      Liverpool Osteoarthritis in Dogs scores were significantly reduced compared to
      preoperative scores. Complications occurred in a total of 19 cases (34.5%; 95%
      confidence interval: 22 to 47.1%); the most common was aseptic loosening of the
      femoral stem [11 cases (20%; 95% confidence interval: 9.4 to 30.6%)]. Following
      multivariable analysis, no risk factors were identified for overall
      complications, but there was a significant association of implant type (first
      generation short stem) with loosening (odds ratio 4.9, 95% confidence interval:
      1.1 to 22.1, P=0.034). CLINICAL SIGNIFICANCE: This study found the Helica hip
      endoprosthesis system to be effective in the management of hip dysplasia and
      osteoarthritis in dogs. Aseptic loosening of the femoral stem remains the most
      common complication but appears to have been significantly reduced with the
      introduction of the second-generation stem.

PMID- 29574979
TI  - Allergic contact dermatitis caused by 1-naphthol, a red coupler, in a purple
      permanent oxidative hair dye.

PMID- 29574980
TI  - Blockade of the renin-angiotensin-aldosterone system in patients with
      arrhythmogenic right ventricular dysplasia: A double-blind, multicenter,
      prospective, randomized, genotype-driven study (BRAVE study).
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy
      characterized by the progressive replacement of cardiomyocytes by fatty and
      fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac
      electrical instability and ventricular arrhythmia. Current treatment for ARVD is
      empirical and essentially based on treatment of arrhythmia. Thus, there is no
      validated treatment that will prevent the deterioration of RV function in
      patients with ARVD. The aim of the BRAVE study is to evaluate the effect of
      ramipril, an angiotensin-converting enzyme inhibitor, on ventricular myocardial
      remodeling and arrhythmia burden in patients with ARVD. Despite the fact that
      myocardial fibrosis is one of the structural hallmarks of ARVD, no study has
      tested an antifibrotic drug in ARVD patients. The trial is a double-blind,
      parallel, multicenter, prospective, randomized, phase 4 drug study. Patients will
      be randomized into 2 groups, ramipril or placebo. The 120 patients (60 per group)
      will be enrolled by 26 centers in France. Patients will be followed up every 6
      months for 3 years. The 2 co-primary endpoints are defined as the difference of
      telediastolic RV volume measured by magnetic resonance imaging between baseline
      and 3 years of follow-up, and the change in arrhythmia burden during the 3 years
      of follow-up. A decrease in RV and/or left ventricular deterioration and in
      arrhythmia burden are expected in ARVD patients treated with ramipril. This
      reduction will improve quality of life of patients and will reduce the number of
      hospitalizations and the risk of terminal heart failure.

PMID- 29574981
TI  - Phosphatidylcholine 36:1 concentration decreases along with demyelination in the
      cuprizone animal model and in post-mortem multiple sclerosis brain tissue.
AB  - Multiple sclerosis is a demyelinating and inflammatory disease. Myelin is
      enriched in lipids, and more specifically, oleic acid. The goal of this study was
      to evaluate the concentration of oleic acid following demyelination and
      remyelination in the cuprizone model, test if these changes occurred in specific
      lipid species, and whether differences in the cuprizone model correlate with
      changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were
      fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11
      days. Demyelination, inflammation, and lipid concentrations were measured in the
      corpus callosum. Standard fatty acid techniques and liquid chromatography
      combined with tandem mass spectrometry were performed to measure concentrations
      of fatty acids in total brain lipids and a panel of lipid species within the
      phosphatidylcholine (PC). Similar measurements were conducted in post-mortem
      brain tissues of multiple sclerosis patients and were compared to healthy
      controls. Five weeks of cuprizone administration resulted in demyelination
      followed by significant remyelination after 11 days of recovery. Compared to
      control, oleic acid was decreased after 5 weeks of cuprizone treatment and
      increased during the recovery phase. This decrease in oleic acid was associated
      with a specific decrease in the PC 36:1 pool. Similar results were observed in
      human post-mortem brains. Decreases in myelin content in the cuprizone model were
      accompanied by decreases in oleic acid concentration and is associated with PC
      36:1 suggesting that specific lipids could be a potential biomarker for myelin
      degeneration. The biological relevance of oleic acid for disease progression
      remains to be verified.

PMID- 29574982
TI  - Reduced root cortical burden improves growth and grain yield under low phosphorus
      availability in maize.
AB  - Root phenes and phene states that reduce the metabolic cost of soil exploration
      may improve plant growth under low phosphorus availability. We tested the
      hypothesis that under low phosphorus, reduced living cortical area (LCA) would
      increase soil exploration, phosphorus capture, biomass, and grain yield. Maize
      genotypes contrasting in LCA were grown in the field and in greenhouse mesocosms
      under optimal and suboptimal phosphorus regimes. Percent LCA in nodal roots
      ranged from 25% to 67%. Plants with 0.2 mm2 less LCA under low phosphorus had 75%
      less root segment respiration, 54% less root phosphorus content, rooted 20 cm
      deeper, allocated up to four times more roots between 60 and 120 cm depth, had
      between 20% and 150% more biomass, 35-40% greater leaf phosphorus content, and
      60% greater grain yield compared with plants with high LCA. Low-LCA plants had up
      to 55% less arbuscular mycorrhizal colonization in axial roots, but this decrease
      was not correlated with biomass or phosphorus content. The LCA components
      cortical cell file number and cortical cell size were important for biomass and
      phosphorus content under low phosphorus. These results are consistent with the
      hypothesis that root phenes that decrease the metabolic cost of soil exploration
      are adaptive under phosphorus stress.

PMID- 29574983
TI  - The 2017 high blood pressure clinical practice guideline: The old and the new.

PMID- 29574985
TI  - A robust LC-MS/MS method for the simultaneous determination of docetaxel and
      voriconazole in rat plasma and its application to pharmacokinetic studies.
AB  - Opportunistic fungal infections are common in immunocompromised cancer patients,
      especially patients undergoing chemotherapy. Because antitumor agents are
      possible to combine with antifungal agents in clinical, it is necessary to study
      drug-drug interaction between antitumor agents and antifungal agents. The aim of
      the study was to explore a method for the simultaneous determination of
      voriconazole and docetaxel in plasma and investigate pharmacokinetic interaction
      of voriconazole and docetaxel in rats. A precise and reliable method using liquid
      chromatography tandem mass spectrometry (LC-MS/MS) was established for the
      simultaneous measure of docetaxel and voriconazole in rat plasma after liquid
      liquid extraction with ethyl acetate. The method was fully validated and
      successfully applied to a pharmacokinetic interaction study of docetaxel and
      voriconazole in rats after single or combined administration. We found that the
      AUC of each drug after coadministration increased compared with that after the
      single administration, which might be caused by interaction at the absorption
      stage or the competitive inhibition on the metabolic enzymes. This established
      method can be utilized to study the detailed mechanism of the drug-drug
      interaction and guide rational drug use in the clinic.

PMID- 29574984
TI  - Endopeptidase inhibition attenuates the contraction induced by big endothelin-1
      of isolated human penile erectile tissue.
AB  - Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal
      polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile
      erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and
      VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in
      an enhancement of CC smooth muscle relaxation. Using the tissue bath technique,
      responses of isolated CC, challenged by noradrenaline (NA, 1 MUm), to increasing
      concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 MUm), CNP and
      VIP (0.1 nm - 1 MUm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm
      - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10
      MUm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force
      generation of 1,200 mg. The contraction was attenuated in the presence of KC
      12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP
      and CNP to 38.7% +/- 15.8% and 61% +/- 13%, respectively, of the initial force.
      The findings might be of significance with regard to future pharmacological
      treatment options for male ED, where an endothelial dysfunction exists.

PMID- 29574986
TI  - Outcome of pregnancies in a large cohort of women with acromegaly.
AB  - OBJECTIVE: To assess the outcome of pregnancies in a large cohort of women with
      acromegaly. DESIGN AND METHODS: This is a retrospective analysis of 31
      pregnancies in 20 patients with acromegaly. RESULTS: Twenty-seven pregnancies
      resulted in healthy offspring, and 4 resulted in abortion. Three patients
      underwent transsphenoidal surgery during pregnancy. IGF-1 levels remained
      elevated during pregnancy in 4 pregnancies and normalized in 23 cases. Fifteen
      cases were followed during pregnancy without any medical or surgical treatment,
      and 13 of these exhibited normal IGF-1 levels. Before or during pregnancy,
      somatostatin receptor ligands usage was not associated with higher risk for
      adverse outcomes. Arterial hypertension worsening (45%) and impairment of glucose
      levels (32%) were the most common complications during pregnancies. There were no
      maternal or neonatal deaths. One woman delivered twins. Two cases of congenital
      malformations and one with foetal macrosomia were observed. Caesarean delivery
      was performed in sixteen cases. CONCLUSION: Our study confirms the impact of
      gestation on IGF-1 levels. However, it also indicates that acromegaly still holds
      an increased risk for worsening of comorbidities, especially in uncontrolled
      patients.

PMID- 29574987
TI  - Novel COL7A1 mutation in a family with bullous dermolysis of the newborn:
      Phenotypic variability associated with a COL7A1 mutation within the same family.

PMID- 29574989
TI  - Editorial.

PMID- 29574988
TI  - Effects of postoperative pain management educational interventions on the
      outcomes of parents and their children who underwent an inpatient elective
      surgery: A randomized controlled trial.
AB  - AIM: To examine the effects of a postoperative pain management educational
      intervention on the outcomes of parents and their children who underwent
      inpatient elective surgery. BACKGROUND: Equipping parents with knowledge and
      skills to manage their children's postoperative pains is essential. Very limited
      studies have examined the effects of educational interventions on parents'
      knowledge, attitudes and use of pharmacological and non-pharmacological pain
      relief methods. DESIGN: Three-group pre- and post-test randomized controlled
      trial. METHODS: Parent-child pairs (N = 152) were recruited from September 2013
      January 2015 and randomly assigned to either the control group or one of the two
      intervention groups. Valid and reliable instruments and diary entries were used
      to collect data at the baseline, 6, 12 and 24 hr and 2 weeks after the surgery.
      IBM SPSS 23.0 was used to analyse the data. RESULTS: Parents reported moderate
      levels of knowledge, attitudes, pain relief methods used and children's
      postoperative pain. Except for parents' knowledge, types and frequencies of non
      pharmacological methods used, there were no statistically significant differences
      among the three groups in parents' attitudes on pain management and pain
      medication, their uses of pain relief strategies (questionnaire data),
      satisfaction with postoperative pain management and children's worst
      postoperative pain in 2 weeks after surgery. CONCLUSION: Education seemed
      effective in improving parents' knowledge and use of non-pharmacological methods,
      but not attitudes, satisfaction with pain management and children's postoperative
      pain. Future studies are needed to develop modern digitalized ways for educating
      and supporting parents to optimize their children's postoperative pain
      management. TRIAL REGISTRATION: This study has been registered with BioMed
      Central Ltd. (Registration No.: ISRCTN24910957).

PMID- 29574990
TI  - The effect of combined pulsed wave low-level laser therapy and mesenchymal stem
      cell-conditioned medium on the healing of an infected wound with methicillin
      resistant Staphylococcal aureus in diabetic rats.
AB  - This study aims to investigate the combined effects of Pulsed wave low-level
      laser therapy (PW LLLT) and human bone marrow mesenchymal stem cell-conditioned
      medium (hBM-MSC-CM) on the microbial flora and tensiometrical properties of an
      infected wound model with methicillin-resistant staphylococcal aureus (MRSA) in
      an experimental model for Type 1 diabetes mellitus (TIDM). TIDM was induced in
      rats by streptozotocin (STZ). One full-thickness excision was made on the backs
      of the rats. Next, the rats were divided into the following groups: Group 1 was
      the control (placebo) group; Group 2 received hBM-MSCs-CM four times; Group 3
      were laser PWLLLT (890 nm, 80 Hz, 0.2 J/cm2 ); and Group 4 received hBM-MSCs-CM
      +LASER. Wounds were infected with MRSA. Microbiological examinations were
      performed on days 4, 7, and 15. Tensiometerical examinations were carried out on
      the 15th day. One-way analysis of variance showed that laser and CM alone and/or
      in combination significantly increases the tensiomerical properties of the
      repaired wounds compared with control wounds. A combination of PW laser and CM
      was statistically more effective than other treated groups. Two-way analysis of
      variance showed that laser and CM alone and/or in combination significantly
      decreases the colony-forming units (CFUs) compared with the control group. The
      application of hBM-MSC-CM and PWlaser alone and/or together significantly
      accelerates the wound-healing process in MRSA-infected cutaneous wounds in TI DM
      in rats. Additionally, a combined application of hBM-MSC-CM and PWlaser
      demonstrates a synergistic effect on the wound-healing process in MRSA-infected
      cutaneous wounds in Type I DM rats.

PMID- 29574991
TI  - Aqueous leaves extract of Madhuca longifolia attenuate diclofenac-induced
      hepatotoxicity: Impact on oxidative stress, inflammation, and cytokines.
AB  - Diclofenac is a Non-Steroidal Anti-inflammatory drug which is used as an
      analgesic. It is known to cause heptotoxicity on over dose and long term usage.
      Madhuca longifolia is an evergreen tree found widely in India that is known to
      have several ethnomedical uses. The aim of our study is to evaluate the
      beneficial effect of the aqueous leaf extract of M. longifolia against diclofenac
      induced toxicity. Rats were dived into five groups of six rats each. Group-I was
      normal control. Group-II was administered with diclofenac (50 mg/kg. b.w./day,
      i.p) on 4th and 5th day. Group-III rats were treated with aqueous leaf extract of
      M. longifolia (500 mg/kg b.w./day, oral) for 5 consecutive days and diclofenac
      (50 mg/kg. b.w./day, i.p) was given on 4th and 5th day. Silymarin (25 mg/kg.
      b.w./day, oral) was used as standard drug which was given to the rats of group-IV
      along with diclofenac on 4th and 5th day. Aqueous leaf extract of M. longifolia
      (500 mg/kg b.w./day, oral) alone was administered in group-V. After the study
      period, the rats were evaluated for liver enzyme markers, antioxidant parameters,
      histopathological changes, and cytokines levels. The hepatic proinflammatory
      mediator cytokines like TNF-alpha, IL-6, and IL-1beta were evaluated through
      ELISA. The protein expression of Caspase-3, COX-2, and NF-kappaB were analysed
      through Western blotting techniques. Aqueous leaves extract of M. longifolia was
      able to normalize the changes caused by diclofenac. Current study indicatesthe
      protective effect of the aqueous leaves extract of M. longifolia against
      diclofenac-induced toxicity.

PMID- 29574992
TI  - Altered DNA methyltransferases promoter methylation and mRNA expression are
      associated with tamoxifen response in breast tumors.
AB  - Tamoxifen is a standard anti-hormone treatment in estrogen receptor positive
      breast carcinoma patients. Unfortunately, about 50% of patients relapse during
      treatment. Promoter hypermethylation contributes to the epigenetic modulation of
      tamoxifen resistance-related genes. To evaluate the contribution of DNMTs
      expression and their promoter methylation as diagnostic biomarkers in development
      of breast malignancy and tamoxifen resistance, the present study was designed and
      107 breast tumors and normal breast tissues were recruited. Methylation-specific
      high-resolution melt curve analysis and quantitative RT-PCR were performed to
      evaluate DNMTs promoter methylation and mRNA expression, respectively. Our
      results indicated that DNMT3A and DNMT3B promoters were demethylated in breast
      tumors as compared to control tissues. The mRNA expression levels of all three
      DNMTs were significantly increased in tumor specimens in comparison to control
      tissues (p < 0.05). Among tumor tissues, DNMT3A promoter methylation was
      significantly higher in tamoxifen sensitive patients (p = 0.001). Overexpression
      of DNMT3A (p = 0.037) and DNMT3B (p < 0.001) mRNA were observed in tamoxifen
      resistance group. Multivariate logistic regression analysis indicated that low
      methylation status of DNMT3A and overexpression of DNMT3B could be as independent
      predictors of disease recurrence. Multivariate Cox regression analysis, revealed
      that high methylation status of DNMT3A could be an independent and favorable
      predictor for disease free survival (p = 0.002) and overall survival (p = 0.026);
      high expression of DNMT1 (p = 0.03) remained significant and unfavorable
      predictive factor for overall survival. In conclusion, our data for the first
      time indicated that low methylation status of DNMT3A promoter and overexpression
      of DNMT3B could contribute to disease recurrence in tamoxifen-treated breast
      cancer patients.

PMID- 29574993
TI  - Marital status and outcomes after myocardial infarction: Observations from the
      Canadian Observational Antiplatelet Study (COAPT).
AB  - While divorced or living alone, patients with stable cardiovascular disease are
      at increased risk for adverse cardiovascular events. The importance of marital
      status following a myocardial infarction (MI) is less clear. We hypothesized that
      marital status may affect cardiovascular outcomes following MI. We analyzed
      outcomes among patients with MI who underwent percutaneous coronary intervention
      from the Canadian Observational Antiplatelet Study (COAPT). Marital status was
      categorized into 3 groups: married/common-law patients living together; never
      married; and divorced, separated, or widowed patients. Patients were followed for
      15 months and our primary outcome was the occurrence of a major adverse
      cardiovascular event (MACE), defined as a composite of mortality, repeat acute
      MI, stroke, or urgent coronary revascularization. Multivariable logistic
      regression models were performed, with married/common-law patients living
      together considered the reference group. Among 2100 patients included in
      analyses, 1519 (72.3%) were married/common-law patients living together, 358
      (17.1%) were separated/divorced/widowed, and 223 (10.6%) patients were never
      married. Dual antiplatelet therapy use after 15 months was similar across groups
      (75.4%, 77.8%, and 73.6%, respectively). The risk of MACE after 15 months was
      similar among married patients living together (12.7%; referent) compared with
      patients who were never married (13.9%; adjusted odds ratio: 1.09, 95% confidence
      interval: 0.58-2.07, P = 0.79) and patients separated/divorced/widowed (14.3%;
      adjusted odds ratio: 0.71, 95% confidence interval: 0.40-1.25, P = 0.23).
      Similarly, the risk of individual endpoints, including mortality, was similar
      across the 3 groups. Among patients stabilized following an MI, we found no
      association between marital status and 15-month outcomes.

PMID- 29574994
TI  - Worse Health-Related Quality of Life at long-term follow-up in patients with
      Cushing's disease than patients with cortisol producing adenoma. Data from the
      ERCUSYN.
AB  - OBJECTIVE: Hypercortisolism in Cushing's syndrome (CS) is associated with
      impaired health-related quality of life (HRQoL), which may persist despite
      remission. We used the data entered into the European Registry on Cushing's
      syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS)
      have worse HRQoL, both before and after treatment than patients with adrenal
      causes (ADR-CS). METHODS: Data from 595 patients (492 women; 83%) who completed
      the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment
      were analysed. RESULTS: At baseline, HRQoL did not differ between PIT-CS (n =
      293) and ADR-CS (n = 120) on both EuroQoL and CushingQoL. Total CushingQoL score
      in PIT-CS and ADR-CS was 41 +/- 18 and 44 +/- 20, respectively (P = .7). At long
      time follow-up (>1 year after treatment) total CushingQoL score was however lower
      in PIT-CS than ADR-CS (56 +/- 20 vs 62 +/- 23; P = .045). In a regression
      analysis, after adjustment for baseline age, gender, remission status, duration
      of active CS, glucocorticoid dependency and follow-up time, no association was
      observed between aetiology and HRQoL. Remission was associated with better total
      CushingQoL score (P < .001), and older age at diagnosis with worse total score (P
      = .01). Depression at diagnosis was associated with worse total CushingQoL score
      at the last follow-up (P < .001). CONCLUSION: PIT-CS patients had poorer HRQoL
      than ADR-CS at long-term follow-up, despite similar baseline scoring. After
      adjusting for remission status, no interaetiology differences in HRQoL scoring
      were found. Age and presence of depression at diagnosis of CS may be potential
      predictors of worse HRQoL regardless of CS aetiology.

PMID- 29574996
TI  - Effect of NaHCO3 treatments on the activity of cell-wall-degrading enzymes
      produced by Penicillium digitatum during the pathogenesis process on grapefruit.
AB  - BACKGROUND: This study was performed to clarify the strategies of Penicillium
      digitatum during pathogenesis on citrus, assessing, on albedo plugs, the effects
      of treatment with sodium bicarbonate (NaHCO3 ), at two different pH values (5 and
      8.3), on cell-wall-degrading enzyme activity over a period of 72 h. RESULTS:
      Treatment with NaHCO3 , under alkaline pH, delayed the polygalacturonase activity
      for 72 h, or 48 h in the case of the pectin lyase, compared with the control or
      the same treatment at pH 5. In contrast, pectin methyl esterase activity rapidly
      increased after 24 h, in plugs dipped in the same solution. In this case, the
      activity remained higher than untreated or pH 5-treated plugs up to 72 h.
      CONCLUSION: The rapid increase in pectin methyl esterase activity under alkaline
      conditions is presumably the strategy of the pathogen to lower the pH, soon after
      the initiation of infection, in order to restore an optimal environment for the
      subsequent polygalacturonase and pectin lyase action. In fact, at the same time,
      a low pH delayed the enzymatic activity of polygalacturonase and pectin lyase,
      the two enzymes that actually cleave the alpha-1,4-linkages between the
      galacturonic acid residues. (c) 2018 Society of Chemical Industry.

PMID- 29574995
TI  - Effect of peer support on diabetes distress: a cluster randomized controlled
      trial.
AB  - AIM: To investigate whether peer support would reduce diabetes distress and
      improve glycaemic control when added to usual diabetes education among adults
      with Type 2 diabetes in China. METHODS: We conducted a cluster randomized trial
      involving 400 adults with Type 2 diabetes from eight communities in Nanjing. All
      participants received usual education for an average of 2 h each month from
      physicians, certified diabetes educators, dieticians, psychologists and podiatric
      nurses. Peer support was led by trained peer leaders and included diabetes
      knowledge- and skills-sharing at least once a month, as well as peer-to-peer
      communication. The primary outcome was diabetes distress measured using the
      Diabetes Distress Scale at 12 months. Secondary outcomes included fasting plasma
      glucose, 2-h postprandial glucose and HbA1c concentration. Outcome data were
      collected from all participants at baseline, 6 months and 12 months. RESULTS:
      From 2012 to 2013, there were 200 participants in each study arm at baseline.
      Compared with the usual education arm, the peer support with usual education arm
      had greater reductions in regimen-related distress (1.4 +/- 0.6 vs 1.2 +/- 0.4;
      P=0.004) and total distress (1.3 +/- 0.4 vs 1.2 +/- 0.3; P=0.038) at 6 months. At
      12 months, the scores for emotional burden (1.2 +/- 0.3 vs 1.4 +/- 0.6; P=0.002),
      physician-related distress (1.1 +/- 0.3 vs 1.3 +/- 0.4; P=0.001) and total scores
      (1.2 +/- 0.3 vs 1.3 +/- 0.4; P=0.002) were significantly lower in the peer
      support with usual education arm than in the usual education arm. Fasting plasma
      glucose levels were lower in the peer support with usual education arm than in
      the usual education arm at 6 months (7.5 +/- 1.95 vs 8.0 +/- 2.2; P=0.044) and 12
      months (7.0 +/- 2.3 vs 7.6 +/- 1.5; P=0.008). CONCLUSIONS: Beyond the benefits of
      usual education, peer support was effective in reducing diabetes distress for
      Type 2 diabetes mellitus. (Clinical Trials Registry no: NCT02119572).

PMID- 29574997
TI  - Fractional ablative carbon dioxide laser followed by topical sodium
      stibogluconate application: A treatment option for pediatric cutaneous
      leishmaniasis.
AB  - BACKGROUND: Leishmaniasis is a protozoan zoonotic parasitic infection with
      cutaneous, mucocutaneous, and visceral manifestations. Israel is endemic for
      cutaneous leishmaniasis, which is a self-limited disease but is associated with
      scarring, which is often a source of psychological and social burden for
      patients. Scars can be especially devastating for children and teenagers. A wide
      range of physical and medical approaches is used to treat cutaneous
      leishmaniasis, among which intralesional injections of sodium stibogluconate rank
      among the most frequently used. Unfortunately, despite being effective, this
      therapeutic modality can be very painful. Fractional ablative laser creates a
      controlled mesh-like pattern of tissue ablation in the skin that promotes dermal
      remodeling and collagen production while at the same time facilitating enhanced
      delivery of topically applied medications. METHODS: Patients were treated with
      fractional ablative carbon dioxide laser followed by immediate topical
      application of sodium stibogluconate. All children were diagnosed with cutaneous
      leishmaniasis prior to treatment initiation.. RESULTS: Ten children were treated.
      One leishmania tropica-positive girl failed to respond. The other nine patients
      achieved clinical cure and demonstrated good to excellent final cosmesis. Self
      rated patient satisfaction and tolerance were high No adverse effects were
      observed or reported during treatment. CONCLUSION: Fractional ablative carbon
      dioxide laser followed by topical sodium stibogluconate application appears to be
      a safe and promising treatment for cutaneous leishmaniasis infection in children.
      Future controlled studies are required to validate these findings and compare
      this technique with traditional approaches.

PMID- 29574998
TI  - Safety and efficacy of enhanced recovery after surgery (ERAS) programs in
      patients undergoing hepatectomy: A prospective randomized controlled trial.
AB  - BACKGROUND AND AIM: Enhanced recovery after surgery (ERAS) programs, following a
      variety of perioperative treatments with evidence-based medical evidence, has
      indicated its validity to accelerate rehabilitation in a wide variety of surgical
      procedures. This randomized controlled trial (RCT) study was implemented to
      verify the safety and efficacy of the perioperative effects in patients
      undergoing hepatectomy with ERAS or with conventional surgery (CS). METHODS: From
      August 2016 to November 2017, according to the inclusion criteria, 160 patients
      with liver diseases were suitable for participating in this experiment. Patients
      before liver resection were randomized into ERAS group (n = 80) and CS group (n =
      80), and then the outcome measures were compared between the two groups. RESULTS:
      Enhanced recovery after surgery group had significantly less complications than
      CS group (P = .009). Compared with CS group, patients in ERAS group had low peak
      of WBCs in postoperative day (POD1), ALT in POD1 and POD3 (P < .05), high value
      of ALB in POD3 and POD5 (P < .05), less pain and higher patient satisfaction (P <
      .001), earlier exhaust, oral feeding, ambulation and extubation time (P <
      .05),and also had less hospital stay and cost (P < .001). There were no
      significant differences in readmission rate (<30 days) between two groups (P =
      .772). CONCLUSIONS: Enhanced recovery after surgery programs applied to patients
      undergoing hepatectomy can safely and effectively relieve stress response, reduce
      the incidence of complications, improve patient satisfaction, accelerate patient
      recovery, reduce financial burden, and bring economic benefits.

PMID- 29574999
TI  - Epidemiological and clinical features of rosacea in Korea: A multicenter cross
      sectional study.
AB  - Rosacea is a common chronic inflammatory skin condition. Although several
      epidemiological and etiologic studies with large sample sizes have been conducted
      on Caucasians, such data regarding Asian populations are lacking. A total of 580
      patients diagnosed with rosacea were enrolled from October 2014 to February 2015
      at 14 general hospitals. Questionnaires, including the standard classification
      and grading system, were used for evaluation. The average age of the patients was
      47.9 years. While 83.8% of patients revealed a single subtype, 16.2% of patients
      revealed mixed subtypes showing two or more subtypes simultaneously.
      Erythematotelangiectatic rosacea (ETR) was the most prevalent subtype. ETR
      combined with papulopustular rosacea showed the highest proportion in the mixed
      subtype group. Mild severity was revealed in 71.9% of patients. The most common
      aggravating factor was emotional changes (51.7%), followed by stress (48.4%).
      Approximately half of the patients (47.4%) showed relatively low awareness of
      rosacea. By identifying the epidemiological and etiologic features in Korea, we
      can suggest valuable clinical avenues for research, education and awareness among
      rosacea patients.

PMID- 29575000
TI  - Validated LC-MS/MS method for the quantification of sciadopitysin in rat plasma
      and its application to pharmacokinetic and bioavailability studies in vivo.
AB  - A sensitive and rapid LC-MS/MS method was developed and validated for
      quantitation of sciadopitysin in rat plasma using amentoflavone as an internal
      standard. Sample processing was accomplished after deproteinization with 150 MUL
      aliquot of acetonitrile. Chromatographic separation was achieved using an Agela
      C18 column with an isocratic mobile phase comprising 2 mm ammonium acetate
      acetonitrile (35:65, v/v) at a flow rate of 0.4 mL/min. Detection was performed
      by selection reaction monitoring on a triple-quadrupole mass spectrometer
      following the transitions m/z 579 -> 547 and 537 -> 375 for sciadopitysin and
      internal standard, respectively, in the negative ionization mode. The calibration
      curve was linear from 2.90 to 1160 ng/mL for sciadopitysin. Intra- and inter-day
      precisions were in the ranges 4.1-11.4 and 5.7-9.1% for sciadopitysin.
      Sciadopitysin was stable under different stability conditions. The validated
      assay was applied to pharmacokinetic and bioavailability studies in rats.

PMID- 29575001
TI  - Aphid (Myzus persicae) feeding on the parasitic plant dodder (Cuscuta australis)
      activates defense responses in both the parasite and soybean host.
AB  - Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host
      tissues to enable fusion between the parasite and host vascular systems, allowing
      Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are
      piercing-sucking herbivores that use specialized stylets to feed on phloem sap.
      Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond
      to aphids attacking the parasite was unknown. Phytohormone quantification,
      transcriptomic analysis and bioassays were performed to determine the responses
      of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green
      peach aphid (GPA; Myzus persicae) on C. australis. Decreased salicylic acid
      levels and 172 differentially expressed genes (DEGs) were found in GPA-attacked
      C. australis, and the soybean hosts exhibited increased jasmonic acid contents
      and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA
      feeding on C. australis increased the resistance of the soybean host to
      subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis
      glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival
      rate. These data strongly suggest that GPA feeding on Cuscuta induces a systemic
      signal, which is translocated to hosts and activates defense against herbivores.

PMID- 29575002
TI  - A defined, plant-based diet utilized in an outpatient cardiovascular clinic
      effectively treats hypercholesterolemia and hypertension and reduces medications.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a major economic burden in the United
      States. CVD risk factors, particularly hypertension and hypercholesterolemia, are
      typically treated with drug therapy. Five-year efficacy of such drugs to prevent
      CVD is estimated to be 5%. Plant-based diets have emerged as effective mitigators
      of these risk factors. HYPOTHESIS: The implementation of a defined, plant-based
      diet for 4 weeks in an outpatient clinical setting may mitigate CVD risk factors
      and reduce patient drug burden. METHODS: Participants consumed a plant-based diet
      consisting of foods prepared in a defined method in accordance with a food
      classification system. Participants consumed raw fruits, vegetables, seeds, and
      avocado. All animal products were excluded from the diet. Participant
      anthropometric and hemodynamic data were obtained weekly for 4 weeks. Laboratory
      biomarkers were collected at baseline and at 4 weeks. Medication needs were
      assessed weekly. Data were analyzed using paired-samples t tests and 1-way
      repeated-measures ANOVA. RESULTS: Significant reductions were observed for
      systolic (-16.6 mmHg) and diastolic (-9.1 mmHg) blood pressure (P < 0.0005),
      serum lipids (P <= 0.008), and total medication usage (P < 0.0005). Other CVD
      risk factors, including weight (P < 0.0005), waist circumference (P < 0.0005),
      heart rate (P = 0.018), insulin (P < 0.0005), glycated hemoglobin (P = 0.002),
      and high-sensitivity C-reactive protein (P = 0.001) were also reduced.
      CONCLUSION: A defined, plant-based diet can be used as an effective therapeutic
      strategy in the clinical setting to mitigate cardiovascular risk factors and
      reduce patient drug burden.

PMID- 29575003
TI  - D-CAST: enhancing communication skills among dental students.

PMID- 29575004
TI  - A simple and selective LC-MS/MS method for quantification of ikarisoside A in rat
      plasma and its application to a pharmacokinetic study.
AB  - Ikarisoside A is a natural flavonoid isolated from Epimedium plants. To further
      evaluate its medicinal potential, a sensitive and robust LC-MS/MS method was
      developed and validated for the assay of ikarisoside A in rat plasma. Orientin
      was used as an internal standard. The electrospray ionization was operated in its
      negative ion mode while ikarisoside A and IS were measured by selected reaction
      monitoring using precursor-to-product ion transitions of m/z 499.1 -> 353.0 and
      m/z 446.9 -> 327.6, respectively. This LC-MS/MS method had good sensitivity (LLOQ
      = 1.5 ng/mL), accuracy (both intra- and inter-day RE <= +/-11.9%) and precision
      (both intra- and inter-day RSD <=8.5%). The pharmacokinetics of ikarisoside A was
      subsequently profiled in Sprague-Dawley rats. Following oral administration (35
      mg/kg), ikarisoside A reached maximum plasma concentration (Cmax , 207.6 +/- 96.7
      ng/mL) attained at 1.10 +/- 0.42 h. Following oral administration, the clearance
      and terminal half-life were 42.9 +/- 26.5 L/h/kg and 3.15 +/- 0.80 h by oral
      route, respectively.

PMID- 29575005
TI  - Axillary Sonography of the Shoulder: An Adjunctive Approach.
AB  - Sonography of the shoulder is widely used to assess various disorders, including
      tendinous diseases of the rotator cuff and the long head of the biceps brachii
      muscle. The shoulder is commonly explored through anterior, superior, and
      posterior approaches, but the inferior axillary approach is rarely considered in
      the literature. However, this technique allows the direct visualization of
      relevant anatomic structures. The aim of this pictorial essay is, first, to
      technically describe this approach and the normal musculoskeletal sonographic
      anatomy of the region and, second, to present the sonographic findings of
      shoulder disorders that may be helpfully explored this technique.

PMID- 29575006
TI  - First-in-man-proof of concept study with molidustat: a novel selective oral HIF
      prolyl hydroxylase inhibitor for the treatment of renal anaemia.
AB  - AIMS: Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal
      anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia
      inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO
      levels dose dependently in preclinical models. We examined the pharmacokinetics,
      safety, tolerability and effect on EPO levels of single oral doses of molidustat
      in healthy male volunteers. METHODS: This was a single-centre, randomized, single
      blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat
      was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol
      based solution. RESULTS: In total, 45 volunteers received molidustat and 14
      received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma
      concentration and area under the concentration-time curve increased dose
      dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase
      in endogenous EPO was observed following single oral doses of molidustat of 12.5
      mg and above. Geometric mean peak EPO levels were 14.8 IU l-1 (90% confidence
      interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l-1 (90%
      confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The
      time course of EPO levels resembled the normal diurnal variation in EPO. Maximum
      EPO levels were observed approximately 12 h postdose and returned to baseline
      after approximately 24-48 h. All doses of molidustat were well tolerated and
      there were no significant changes in vital signs or laboratory safety parameters.
      CONCLUSIONS: Oral administration of molidustat to healthy volunteers elicited a
      dose-dependent increase in endogenous EPO. These results support the ongoing
      development of molidustat as a potential new treatment for patients with renal
      anaemia.

PMID- 29575007
TI  - Novel organometallic chloroquine derivative inhibits tumor growth.
AB  - Autophagy has emerged as a mechanism critical to both tumorigenesis and
      development of resistance to multiple lines of anti-cancer therapy. Therefore,
      targeting autophagy and alternative cell death pathways has arisen as a viable
      strategy for refractory tumors. The anti-malarial 4-aminoquinoline compounds
      chloroquine and hydroxychloroquine are currently being considered for re
      purposing as anti-cancer therapies intended to sensitize different tumors by
      targeting the lysosomal cell death pathway. Here, we describe a novel
      organometallic chloroquine derivative, cymanquine, that exhibits enhanced
      bioactivity compared to chloroquine in both normal, and reduced pH tumor
      microenvironments, thus overcoming a defined limitation of traditional 4
      aminoquinolines. In vitro, cymanquine exhibits greater potency than CQ in a
      diverse panel of human cancer cell lines, including melanoma, in both normal pH
      and in reduced pH conditions that mimic the tumor microenvironment. Cymanquine
      treatment results in greater lysosomal accumulation than chloroquine and induces
      lysosomal dysfunction leading to autophagy blockade. Using a mouse model of
      vemurafenib-resistant melanoma, cymanquine slowed tumor growth greater than
      hydroxychloroquine, and when used in combination with vemurafenib, cymanquine
      partially restored sensitivity to vemurafenib. Overall, we show that cymanquine
      exhibits superior lysosomal accumulation and autophagy blockade than either
      chloroquine or hydroxychloroquine in vitro; and in addition to its high level of
      tolerability in mice, exhibits superior in vivo efficacy in a model of human
      melanoma.

PMID- 29575008
TI  - Drought and increased CO2 alter floral visual and olfactory traits with context
      dependent effects on pollinator visitation.
AB  - Climate change can alter species interactions essential for maintaining
      biodiversity and ecosystem function, such as pollination. Understanding the
      interactive effects of multiple abiotic conditions on floral traits and
      pollinator visitation are important to anticipate the implications of climate
      change on pollinator services. Floral visual and olfactory traits were measured
      from individuals of four forb species subjected to drought or normal water
      availability, and elevated or ambient concentrations of CO2 in a factorial
      design. Pollinator visitation rates and community composition were observed in
      single-species and multi-species forb assemblages. Drought decreased floral
      visual traits and pollinator visitation rates but increased volatile organic
      compound (VOC) emissions, whereas elevated CO2 positively affected floral visual
      traits, VOC emissions and pollinator visitation rates. There was little evidence
      of interactive effects of drought and CO2 on floral traits and pollinator
      visitation. Interestingly, the effects of climate treatments on pollinator
      visitation depended on whether plants were in single- or multi-species
      assemblages. Components of climate change altered floral traits and pollinator
      visitation, but effects were modulated by plant community context. Investigating
      the response of floral traits, including VOCs, and context-dependency of
      pollinator attraction provides additional insights and may aid in understanding
      the overall effects of climate change on plant-pollinator interactions.

PMID- 29575009
TI  - The efficacy of fluoxetine in BMS-A cross-over study.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is an intraoral burning or dysaesthetic
      sensation, recurring daily for more than two hours during the period longer than
      3 months. The objective was to evaluate and analyse the efficacy of serotonin
      reuptake inhibitor fluoxetine on psychological factors, as well as on pain in
      participants with BMS. METHODS: In a 6-month study, 100 participants with primary
      and secondary BMS were divided into two groups-fluoxetine and control (placebo)
      and examined by the dentist and the neurologist. Depression and anxiety were
      estimated by Hamilton Scale for Depression (HAM-D) and Anxiety (HAM-A) and Beck
      Depression Inventory (BDI) and the pain intensity by visual analogue scale (VAS).
      RESULTS: Mean age of the participants was 60.33 in fluoxetine group and 67.4 in
      control group. Most of the participants were female-74% in the fluoxetine and 78%
      in the control group. Statistical difference between the fluoxetine and the
      control group was found in HAM-D results (P < .05). Values of other scales and
      VAS decreased significantly after the therapy in both groups (P < .05).
      CONCLUSIONS: Our trial results indicate that fluoxetine therapy not only improves
      the psychological status of participants with BMS but also fluoxetine decreases
      the intensity of pain in these patients.

PMID- 29575010
TI  - Impact of peer support on inpatient and outpatient payments among people with
      Type 2 diabetes: a prospective cohort study.
AB  - AIM: To investigate the impact of a low-cost diabetes peer-support intervention,
      aimed at reducing inpatient and outpatient care utilization and healthcare
      payments, by conducting a cohort study that followed up a randomized controlled
      trial. METHODS: A total of 1121 adults with Type 2 diabetes were recruited
      through general practices in Cambridgeshire and Hertfordshire, UK, and were
      followed up for 3.25 financial years after 8-12 months of one-to-one, group or
      combined diabetes peer support and usual care. Use of, and payments for inpatient
      and outpatient services were fully recorded in the follow-up. Adjusted mean
      inpatient and outpatient payments per person were estimated using a two-part
      model after adjusting for baseline characteristics. RESULTS: The mean age of the
      recruited adults was 65.6+/-11.4 years, 60.4% were male, and 16.8% were insulin
      treated. Compared with the control group, less healthcare utilization (especially
      non-elective inpatient care and outpatient consultations) was observed in each of
      the intervention groups, particularly the combined intervention group. Over the
      course of 3.25 financial years, significant reductions of 41% (L909.20 per head)
      were observed for overall inpatient payments (P<0.0001), 51% (L514.67 per head)
      for non-elective inpatient payments (P=0.005) in the combined intervention group,
      and 34% (L413.30 per head) and 32% (L388.99 per head) for elective inpatient
      payments in the one-to-one (P=0.029) and combined intervention (P=0.048) groups,
      respectively. CONCLUSIONS: Type 2 diabetes peer support, whether delivered using
      a one-to-one, group or combined approach was associated with reduced inpatient
      care utilization (particularly non-elective admissions) and payments over 3.25
      years.

PMID- 29575011
TI  - Stroke localization and classification using microwave tomography with k-means
      clustering and support vector machine.
AB  - For any chance for stroke patients to survive, the stroke type should be
      classified to enable giving medication within a few hours of the onset of
      symptoms. In this paper, a microwave-based stroke localization and classification
      framework is proposed. It is based on microwave tomography, k-means clustering,
      and a support vector machine (SVM) method. The dielectric profile of the brain is
      first calculated using the Born iterative method, whereas the amplitude of the
      dielectric profile is then taken as the input to k-means clustering. The cluster
      is selected as the feature vector for constructing and testing the SVM. A
      database of MRI-derived realistic head phantoms at different signal-to-noise
      ratios is used in the classification procedure. The performance of the proposed
      framework is evaluated using the receiver operating characteristic (ROC) curve.
      The results based on a two-dimensional framework show that 88% classification
      accuracy, with a sensitivity of 91% and a specificity of 87%, can be achieved.
      Bioelectromagnetics. 39:312-324, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29575012
TI  - High expression of glutamate-ammonia ligase is associated with unfavorable
      prognosis in patients with ovarian cancer.
AB  - Glutamate-ammonia ligase (GLUL), which is also called GS (glutamine synthetase),
      is the enzyme that catalyzes the synthesis of glutamine from glutamate and
      ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in
      the ovarian cancer patients was associated with worse disease-free survival (DFS)
      and overall survival (OS). In addition, GLUL was heterogeneously expressed in
      various ovarian cancer cells. The mRNA and protein expression levels of GLUL in
      NIH:OVCAR-3 and ES-2 cells were obviously higher than that in the other types of
      ovarian cancer cells. Knockdown of GLUL in NIH:OVCAR-3 or ES-2 cells could
      significantly decrease the proliferation ability. Furthermore, GLUL knockdown
      markedly inhibited the p38 MAPK signaling pathway in NIH:OVCAR-3 or ES-2 cells.
      Our findings suggest that decreasing expression of GLUL may be a new approach
      that can be used for ovarian cancer treatment.

PMID- 29575013
TI  - MicroRNA-374b inhibits cervical cancer cell proliferation and induces apoptosis
      through the p38/ERK signaling pathway by binding to JAM-2.
AB  - Cervical cancer (CC) remains a highly prevalent cancer and mortality globally
      among women globally. The aim of the present study was to assess the ability of
      miR-374b to regulate CC cells through JAM-2, whilst exploring whether the
      underlying mechanism and its relation to the p38/ERK signaling pathway. During
      the study, microRNA-374b (miR-374b) was observed to have been expressed at a low
      level among CC tissues. Hence, a series of miR-374b mimics, miR-374b inhibitors,
      siRNA against JAM-2, SB202190 (an inhibitor for p38), and PD98059 (an inhibitor
      for ERK) were introduced to treat CC Siha cells and normal cervical Ect1/E6E7
      cells. MTT, flow cytometry, scratch test, and transwell assays were applied to
      determine cell viability, apoptosis, migration, and invasion. The inhibitory role
      of the p38/ERK signaling pathway was observed in the CC cells treated with miR
      374b mimics or siRNA against JAM-2. miR-374b mimic exposure was found to reduce
      cell viability, migration, and invasion, but induce apoptosis. MiR-374b inhibitor
      exposure was observed to have induced effects on the CC cells in a contrary
      manner to those induced by that of the miR-374b mimics. The key findings of the
      study demonstrated that miR-374b significantly inhibits cell proliferation,
      migration, and invasion through the blockade of the p38/ERK signaling pathway
      activation, as well as negatively binding to JAM-2, highlighting its potential as
      a therapeutic target for CC.

PMID- 29575014
TI  - Vision testing in microsurgery subspecialties: Does it matter?

PMID- 29575015
TI  - Duct-to-mucosa versus dunking techniques of pancreaticojejunostomy after
      pancreaticoduodenectomy: Do we need more trials? A systematic review and meta
      analysis with trial sequential analysis.
AB  - BACKGROUND: Pancreaticojejunostomy (PJ is the most widely used reconstruction
      technique after pancreaticoduodenectomy. Despite several randomized trials, the
      ideal technique of pancreaticojejunostomy remains debatable. We planned a meta
      analysis of randomized trials comparing the two most common techniques of PJ
      (duct-to-mucosa and dunking) to identify the best available evidence in the
      current literature. METHODS: We searched the Pubmed/Medline, Web of science,
      Science citation index, Google scholar and Cochrane Central Register of
      Controlled Trials electronic databases till October 2017 for all English language
      randomized trials comparing the two approaches. Statistical analysis was
      performed using Review Manager (RevMan), Version 5.3. Copenhagen: The Nordic
      Cochrane Center, The Cochrane Collaboration, 2014 and results were expressed as
      odds ratio for dichotomous and mean difference for continuous variables. P-value
      <= 0.05 was considered significant. Trial sequential analysis was performed using
      TSA version 0.9.5.5 (Copenhagen: The Copenhagen Trial Unit, Center for Clinical
      Intervention Research, 2016). RESULTS: A total of 8 trials were included, with a
      total of 1043 patients (DTM: 518; Dunking: 525). There was no significant
      difference between the two groups in terms of overall as well as clinically
      relevant POPF rate. Similarly, both groups were comparable for the secondary
      outcomes. Trial sequential analysis revealed that the required information size
      had been crossed without achieving a clinically significant difference for
      overall POPF; and though the required information size had not been achieved for
      CR-POPF, the current data has already crossed the futility line for CR-POPF with
      a 10% risk difference, 80% power and 5% alpha error. CONCLUSION: This meta
      analysis found no significant difference between the two techniques in terms of
      overall and CR-POPF rates. Further, the existing evidence is sufficient to
      conclude lack of difference and further trials are unlikely to result in any
      change in the outcome. (CRD42017074886).

PMID- 29575016
TI  - Simultaneous determination of twelve polar pteridines including dihydro- and
      tetrahydropteridine in human urine by hydrophilic interaction liquid
      chromatography with tandem mass spectrometry.
AB  - Pteridines and their derivatives are important cofactors in the process of cell
      metabolism, and the level of urinary excretion of these compounds is considered
      as an important clinical criterion. In this work, a new separation method
      involving hydrophilic interaction chromatography (HILIC) with tandem mass
      spectrometric detection has been developed for the simultaneous analysis of 12
      pteridines including oxidized, di- and tetrahydroforms, namely neopterin, 7,8
      dihydroneopterin, biopterin, 7,8-dihydrobiopterin, 5,6,7,8-tetrahydrobiopterin,
      dimethylpterin, dimethyltetrahydropterin, pterin, isoxanthopterin, xanthopterin,
      sepiapterin and pterin-6-carboxylic acid, in human urine without oxidative
      pretreatments. The stabilizing agent (dithiothreitol) at various concentrations
      and the stability of oxidized, di- and tetrahydroforms during the sample's short
      term storage and processing and of the extracts were tested. In the developed
      method, 12 pteridines were chromatographically separated on an ZIC-HILIC column
      by gradient elution, and the run time was 20 min. Matrix effect was evaluated and
      several dilutions of urine were tested in order to study the evolution of signal
      suppression. Spiked recovery studies demonstrated that the technique was both
      accurate (83.1-116.7%) and precise (RSD 1.4-15.6%). Finally, several clinical
      urine specimens without oxidative pretreatments were examined with the new
      technique and compared with previous reports.

PMID- 29575018
TI  - The Diversification of Early Emerging Metazoans: A Window into the Evolution of
      Animal Multicellularity.
AB  - The biannual international workshop entitled "The diversification of early
      emerging metazoans: A window into animal evolution?" took place at the
      Evangelische Akademie Tutzing, Germany, 11-14. September 2017. It was organized
      by Thomas Bosch (Kiel), Thomas Holstein (Heidelberg), and Ulrich Technau
      (Vienna), and it was sponsored by the Deutsche Forschungsgemeinschaft (DFG). The
      meeting gathered over 140 researchers to discuss the contribution of non
      bilaterian metazoan models (Porifera, Ctenophora, Placozoa, and Cnidaria) to our
      understanding of: a. The evolution of metazoan developmental processes; b.
      Fundamental molecular mechanisms underlying metazoan features; and c. The complex
      interactions that animals establish with their environment.

PMID- 29575017
TI  - An update on the clinical evidence that supports biosimilar approvals in Europe.
AB  - AIM: Sponsors and regulators have more than 10 years of experience with the
      development of biosimilars in Europe. However, the regulatory pathway is still
      evolving. The present article provides an update on biosimilar development in
      practice by reviewing the clinical development programmes of recently approved
      biosimilars in Europe. METHODS: We used the European public assessment reports
      (EPARs) which are published by the European Medicines Agency (EMA) for a
      comparison of the clinical development programmes of the 37 approved biosimilars
      in Europe. Here, we present novel strategies in the development of biosimilars by
      focusing specifically on the 17 biosimilars that have gained approval in the last
      year, but we also compare additional key characteristics for all approved
      biosimilars. RESULTS: The high variability of the clinical development strategies
      that we found previously was confirmed in the present analysis. Compared with
      earlier biosimilar applications, more nonstandard development strategies have
      been used recently. This includes, for example, applications without any studies
      in patients, and more complex study designs. During this study, we found that the
      EPARs for biosimilars seem to be improving; however, we identified important
      details which were still often missing. We provide a proposal for a checklist of
      the minimum information that should be included in biosimilar EPARs for giving
      the general public insights into the rationale for the approval of biosimilars.
      CONCLUSIONS: European regulators still seem to be open to consider approaches
      that differ from the guidelines or previous applications, as long as
      justification is provided.

PMID- 29575019
TI  - Reduced vision, refractive errors and health-related quality of life among
      adolescents in rural China.
AB  - BACKGROUND: To determine the associations of reduced presenting visual acuity
      (VA), refractive errors and health-related quality of life (HRQoL) in healthy
      adolescents in rural China. METHODS: A total of 2,235 grade 7 students without
      systemic medical problems from 10 middle schools aged 13-14 years in Mojiang, a
      small county located in southwestern China, were included in the analysis.
      Reduced VA was defined as presenting VA of worse than 6/12 in the presence of an
      ophthalmic aetiology which could be identified. The refractive status of each
      participant was measured after cycloplegia using an autorefractor. The Pediatric
      Quality of Life Inventory Version 4.0 Generic Core Scales was used for measuring
      HRQoL of the participants. RESULTS: Among all the participants included in the
      data analysis, 279 (12.5 per cent) individuals were affected by reduced VA based
      on the better-seeing eye data. After adjusting for the effect of gender, body
      mass index, the education level of the father, and the use of a corrective
      device, the total (adjusted mean difference: -3.27; 95 per cent confidence
      interval [CI] -4.95 to -1.59; p = 0.01), social functioning (adjusted mean
      difference: -3.44; 95 per cent CI -5.87 to -1.01; p = 0.02) and school
      functioning scores (adjusted mean difference: -3.12; 95 per cent CI -5.89 to 
      0.35; p = 0.04) of the adolescents with reduced presenting VA were significantly
      lower compared with those with normal vision. The associations between corrected
      refractive errors and HRQoL were not significant. CONCLUSIONS: Healthy
      adolescents with reduced VA reported lower HRQoL scores including total, social
      functioning and school functioning scores, compared with those with normal
      vision.

PMID- 29575020
TI  - The VFH1 (YLL056C) promoter is vanillin-inducible and enables mRNA translation
      despite pronounced translation repression caused by severe vanillin stress in
      Saccharomyces cerevisiae.
AB  - Vanillin, furfural and 5-hydroxymethylfurfural (HMF) are representative
      fermentation inhibitors generated during the pretreatment process of
      lignocellulosic biomass in bioethanol production. These biomass conversion
      inhibitors, particularly vanillin, are known to repress translation activity in
      Saccharomyces cerevisiae. We have reported that the mRNAs of ADH7 and BDH2 were
      efficiently translated under severe vanillin stress despite marked repression of
      overall protein synthesis. In this study, we found that expression of VFH1
      (YLL056C) was also significantly induced at the protein level by severe vanillin
      stress. Additionally, we demonstrated that the VFH1 promoter enabled the protein
      synthesis of other genes including GFP and ALD6 under severe vanillin stress. It
      is known that transcriptional activation of VFH1 is induced by furfural and HMF,
      and we verified that Vfh1 protein synthesis was also induced by furfural and HMF.
      The null mutant of VFH1 delayed growth in the presence of vanillin, furfural and
      HMF, indicating the importance of Vfh1 for sufficient tolerance against these
      inhibitors. The protein levels of Vfh1 induced by the inhibitors tested were
      markedly higher than those of Adh7 and Bdh2, suggesting the superior utility of
      the VFH1 promoter over the ADH7 or BDH2 promoter for breeding optimized yeast
      strains for bioethanol production from lignocellulosic biomass.

PMID- 29575021
TI  - Low frequency of soya allergy in peanut-allergic children: Relevance to allergen
      labelling on medicines.

PMID- 29575022
TI  - Prevalence and sonographic features of ectopic thyroidal thymus in children: A
      retrospective analysis.
AB  - PURPOSE: To assess the prevalence of ectopic thyroidal thymus tissue detected by
      sonography (US) in children and to analyze the US features. METHODS: We
      retrospectively reviewed images of 216 children who had undergone a thyroid or
      neck US examination from February 2015 to June 2015. Lesions within or adjacent
      to the thyroid gland that showed echopatterns consistent with thymic tissue were
      diagnosed as ectopic thyroidal thymus tissue. Lesions were reviewed according to
      their side, location, level, size, shape, echo pattern, internal content, and
      vascularization. RESULTS: A total of 216 children (119 girls, 97 boys) with a
      mean +/- SD age of 8.6 +/- 5.2 years were enrolled the study.Thirty children
      (13girls, 17 boys) (13.9%) had 35 lesions compatible with ectopic thyroidal
      thymus tissue.Nine children had intrathyroidal (4.2%) and 21 children had
      extrathyroidal (9.7%) ectopic thymus tissue.The mean +/- SD ages of the children
      with and without ectopic thyroidal thymus tissue were 6.0 +/- 3.6 years and 9.1
      +/- 5.2 years, respectively (P = .002). Twenty-five of the lesions were
      extrathyroidal and 10 were intrathyroidal. All extrathyroidal and most (8/9)
      intrathyroidal ectopic thymuses had fusiform shape with well demarcated contours.
      Ectopic thymuses were located either in the midportion (n = 23) or lower portion
      of the neck (n = 12). Both extrathyroidal and intrathyroidal ectopic thymuses
      showed typical hypoechoic (n = 22/25, n = 9/10, respectively) or hyperechoic (n =
      3/25, n = 1/10, respectively) echo patterns with internal linear and punctate
      echoes. CONCLUSIONS: Ectopic thyroidal thymic tissue is common in children.
      Radiologists should be vigilant about the unique US features of ectopic thyroidal
      thymus, including a hypo- and hyper-echoic echo pattern with multiple linear and
      punctate echoes, a fusiform shape, well-demarcated contours, and middle or low
      lying location to differentiate it from other neck or thyroid lesions.

PMID- 29575023
TI  - Progression and new onset of nonalcoholic fatty liver disease in living kidney
      donors compared to healthy controls.
AB  - BACKGROUND: There is growing evidence linking nonalcoholic fatty liver disease
      (NAFLD) with reduced glomerular filtration rate (GFR). Living kidney donors do
      not have underlying kidney disease, but have reduced GFR as a result of
      nephrectomy. Whether kidney donation is associated with a higher risk for
      development or progression of NAFLD is currently unknown. METHODS: Retrospective
      evaluation of metabolic parameters and sonographic evidence of NAFLD were
      performed in 232 living kidney donors and 162 healthy controls. RESULTS: A total
      of 25 donors and 44 controls had NAFLD at baseline. During a mean follow-up of
      6.8 years, 6 donors (24%) and 17 controls (38.6%) (P = .29) had a remission of
      NAFLD, related with decreased body mass index (BMI). The progression of NAFLD
      fibrosis score was similar in both groups. New onset of NAFLD was observed in 14
      (6.8%) donors and 13 (11.01%) controls (P = .211), and was related to increased
      BMI and a higher baseline Fatty Liver Index score. Neither eGFR nor urine albumin
      excretion in the donors were related to new onset or progression of NAFLD.
      CONCLUSIONS: Reduced kidney function secondary to kidney donation is not
      associated with increased incidence or progression of NAFLD.

PMID- 29575024
TI  - Toxicity of silver nanoparticles to Lumbriculus variegatus is a function of
      dissolved silver and promoted by low sediment pH.
AB  - Toxicity of silver nanoparticles (AgNPs) to benthic organisms is a major concern.
      The use of AgNPs in industry and consumer products leads to increasing release of
      AgNPs into the aquatic environment-sediments being the major sink. Effects of
      sediment pH on the toxicity of AgNPs to benthic oligochaeta Lumbriculus
      variegatus were studied in a 23-d toxicity test. Artificially prepared sediments
      (pH 5 and 7) were spiked with varying concentrations of uncoated AgNP,
      polyvinylpyrrolidone (PVP)-coated AgNP, and silver nitrate (AgNO3 ) as dissolved
      Ag reference. Number of individuals and biomass change were used as endpoints for
      the toxicity. The toxic effects were related to the bioaccessible concentration
      of dissolved Ag in the sediments, assessed with a 2-step extraction procedure.
      The toxicity of 2 AgNPs was similar and greatly enhanced in the acidic sediment.
      Because the toxic effects were well related to the bioaccessible concentration of
      dissolved Ag in the sediments, the toxicity of sediment-associated AgNPs to L.
      variegatus is suggested to be a function of dissolved Ag rather than a result
      from NP-specific modes of toxicity. Environ Toxicol Chem 2018;37:1889-1897. (c)
      2018 SETAC.

PMID- 29575025
TI  - Long-term outcome of surgical treatment of peri-implantitis. A 2-11-year
      retrospective study.
AB  - OBJECTIVE: To assess long-term clinical and radiological outcomes of surgical
      treatment of peri-implantitis. MATERIAL AND METHODS: Files and radiographs from
      50 patients who had received surgical treatment for peri-implantitis were
      analyzed. Data on clinical characteristics prior to surgical therapy and at
      latest follow-up were obtained. In each radiograph, the marginal bone level was
      assessed at the mesial and distal aspects of the affected implants. The treatment
      included oral hygiene instruction, professional supra-mucosal instrumentation,
      and surgical therapy aiming at pocket elimination. Following flap elevation and
      removal of inflamed tissue, the affected implant was cleaned using gauze soaked
      in saline. Calculus was removed. When indicated, osseous re-contouring was
      carried out to facilitate pocket elimination. Flaps were adjusted, sutured, and
      compressed to the crestal bone. Supportive therapy including oral hygiene control
      was provided with 4-month intervals. RESULTS: Treatment was effective in
      resolving the inflammatory condition as documented by marked reduction in peri
      implant probing depth and bleeding on probing scores together with crestal bone
      level preservation. Treatment outcome was significantly better at implants with
      non-modified surfaces than at implants with modified surfaces. The probability of
      an implant to exhibit no further bone loss or bone gain after treatment was high
      if the peri-implant mucosa at the site presented with shallow pockets and the
      absence of bleeding on probing at follow-up. CONCLUSIONS: The results of the
      study revealed that (i) surgical treatment of peri-implantitis was effective in
      the long-term, (ii) outcome was better at implants with non-modified than with
      modified surfaces, and (iii) preservation of crestal bone support was consistent
      with healthy peri-implant tissue conditions.

PMID- 29575026
TI  - AG-1031 induced autophagic cell death and apoptosis in C6 glioma cells associated
      with Notch-1 signaling pathway.
AB  - Glioma is the most common primary brain tumor with high morbidity and poor
      prognosis. The effect of AG-1031, which is developed as an antineoplastic drug,
      on C6 glioma cells is still not clear. The aim of this research was to explore
      the effect of AG-1031 on C6 cells, and tried to find out its potential mechanism
      on cytotoxicity of C6 cells. The 3-(4,5-dimethylthiazol -2-yl) -2,5-
      diphenyltetrazolium bromide (MTT) assay showed that AG-1031 inhibited cell
      viability in a concentration-dependent manner, whereas 3-methyadenine (3-MA)
      reduced this effect. Results from hoechst 33342 staining and Western blot assay
      indicated that AG-1031 induced C6 cell apoptosis. Western blot assay presented
      that AG-1031 notably increased the LC3-II/LC3-I ratio and decreased the
      expression of P62. Besides, our results showed that bafilomycin A1 increased the
      expression of LC3-II in cells treated with AG-1031, which indicated that AG-1031
      can increase autophagy in C6 cells. Meanwhile, Western blot assay showed that AG
      1031 can inhibit Notch-1 signaling by testing relative protein expressions. The
      expression of the intracellular domain of Notch (NICD) also decreased according
      to immunofluorescence assay. Additionally, the activation of Notch-1 signaling
      alleviated AG-1031-induced autophagic cell death and apoptosis. Furthermore,
      phosphorylated Akt and its downstream effector mechanistic target of rapamycin
      (mTOR) were reduced with AG-1031. These results suggest that AG-1031 may induce
      autophagic cell death through the inhibition of Akt-mTOR signaling pathway by
      down-regulating Notch-1 signaling pathway and activating apoptosis in C6 cells
      via Notch-1 signaling, which develops a new target spot to treat glioma in the
      future.

PMID- 29575027
TI  - Literature Review.

PMID- 29575028
TI  - Ultrasound and the Evaluation of Pediatric Thyroid Malignancy: Current
      Recommendations for Diagnosis and Follow-up.
AB  - Ultrasound (US) plays a critical role in the evaluation, treatment, screening,
      and surveillance of thyroid malignancy in pediatric patients. This review aims to
      summarize recent advances in this topic. Improvements in imaging technology have
      amplified the advantage of US and US-guided fine-needle aspiration biopsy for
      thyroid nodule evaluation, cancer diagnosis, and surgical planning. Ultrasound
      has a definitive screening role for early cancer detection in high-risk patients,
      including those with a history of radiation exposure from childhood treatments,
      environmental radiation disasters, or hereditary/familial cancer syndromes.
      Finally, US is a key component of lifelong surveillance for recurrence among
      pediatric thyroid cancer survivors.

PMID- 29575029
TI  - A Practical Approach to Quantitative Grayscale Ultrasound Analysis of Hepatic
      Steatosis in Pediatric Patients Using a Picture Archiving and Communication
      System-Based Tool.
AB  - OBJECTIVES: To evaluate the efficacy of a picture archiving and communication
      system (PACS)-based ultrasound (US) quantification technique for diagnosis of
      hepatic steatosis in a pediatric population. METHODS: Abdominal US images of 49
      pediatric patients (<=18 years) with histopathologically proven diagnoses of
      hepatic steatosis (n = 17), nonsteatotic liver disease (n = 19), and a normal
      liver (n = 13) were retrospectively reviewed. Patient demographics, the fibrosis
      stage, and the steatosis grade were obtained from the database. Quantitative
      grayscale measurements of the echo intensity level of the liver and kidneys were
      performed on the US images using the PACS measuring tool. The hepatorenal ratio
      was obtained by dividing mean liver by mean kidney values. The heterogeneity
      index for the liver was calculated by dividing the liver standard deviation by
      mean liver values. Hepatorenal ratio and heterogeneity index values of the 3
      groups were correlated with pathologic results and compared by a 1-way analysis
      of variance. A receiver operating characteristic curve analysis was performed,
      and cutoff values were determined. RESULTS: The hepatorenal ratio of the hepatic
      steatosis group was significantly greater than those of the control and
      nonsteatotic liver disease groups (P < .001). The heterogeneity index of the
      hepatic steatosis group was significantly greater than that of the control group
      (P = .046). For a hepatorenal ratio cutoff value of 1.5, 88.2% sensitivity, 91.4%
      specificity, 88.3% positive predictive value, and 94.1% negative predictive value
      were obtained for predicting hepatic steatosis. CONCLUSIONS: PACS-based
      quantitative grayscale US quantification is a safe, accurate, and easily
      applicable objective method for the diagnosis of hepatic steatosis in children. A
      hepatorenal ratio of greater than 1.5 can be used as a conservative parameter,
      permitting increased confidence in discriminating hepatic steatosis from other
      conditions.

PMID- 29575030
TI  - Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of
      Alzheimer's disease during lifespan.
AB  - : Alzheimer's disease (AD) is the most common form of dementia and one of the
      major causes of disability and dependency in older people. Accumulating evidences
      link gut microbiota with different diseases and its relationship with
      neurodegenerative diseases is becoming most intriguing. This study was aimed to
      compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well-established
      deterministic mouse model of AD, with their C57BL/6 wild-type (WT) littermates.
      Faecal samples were collected from 3-, 6- and 24-month-old mice and analysed by
      pyrosequencing of the V1-V3 region of the bacterial 16S rRNA genes. Bacterial
      profiles were similar in all young mice (3 months old), and started to diverge so
      that 6-month-old WT and TG mice had different and more diverse microbiota. During
      ageing, Turicibacteriaceae (typical mice bacterial group) and Rikenellaceae
      increased in all groups, although total Bacteroidetes remained stable. TG mice
      were characterized by an increase in Proteobacteria after 6 months, particularly
      the genus Sutterella (Betaproteobacteria), interestingly also increased in autism
      disorder. Also, the inflammation related family Erysipelotrichaceae was more
      abundant in TG mice at 24 months compared to wild-type control. In summary, AD
      pathology in mice shifts the gut microbiota towards profiles that share features
      with autism and inflammatory disorders. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Alzheimer's disease is a neurodegenerative disease and neuroinflammation in the
      central nervous system appears to have a pivotal role. Using the transgenic
      APP/PS1 (TG) mouse model, we successfully characterized how AD pathology shifted
      gut microbiota composition during ageing towards an inflammation related
      bacterial profile related to Proteobacteria and Erysipelotrichaceae and suggest
      that these changes could contribute to disease progression and severity.
      Microbiota-targeted interventions could therefore represent a strategy to
      postpone disease symptoms.

PMID- 29575032
TI  - Non-surgical treatment with basic fibroblast growth factor for atrophic scars in
      acne vulgaris.

PMID- 29575031
TI  - Parenting style impacts cognitive and behavioural outcomes of former preterm
      infants: A systematic review.
AB  - We sought to evaluate published evidence in aggregate regarding the impact of
      parenting style on the cognitive and behavioural outcomes of former preterm
      infants. We searched 5 databases using germane MeSH terms. Parenting style was
      defined as any descriptor of parenting using >=2 dimensions on published
      parenting axes. We evaluated studies for quality of evidence and strength of
      recommendations using standardized tools and categorized summative
      recommendations by parenting axis and child outcome. Twenty-seven articles met
      our inclusion criteria. Parental responsivity is the only parenting axis strongly
      associated with both improved child cognition and behaviour. Parental
      demandingness is associated only with improved child cognition, and parental
      warmth and rejection are associated only with child behaviour. Parental coercion
      is not associated with subsequent child outcomes. Parental responsivity may be
      essential in optimizing neurodevelopment in former preterm infants. More targeted
      studies are needed to inform this relationship and identify opportunities for
      intervention.

PMID- 29575034
TI  - Accommodative accuracy by retinoscopy versus autorefraction spherical equivalent
      or horizontal meridian power.
AB  - BACKGROUND: To assess agreement between accommodative lag by monocular estimation
      method (MEM) retinoscopy and Nott retinoscopy compared to open-field
      autorefraction using spherical equivalent versus power in the 180 meridian for
      both children and adults. METHODS: Twenty-six children aged 7-16 years (mean: 9.9
      +/- 2.3) and 27 adults aged 22-29 years (mean: 24.2 +/- 1.7) participated.
      Accommodative lag was measured by examiners with autorefraction and separate
      examiners using MEM and Nott retinoscopy while subjects viewed 6/18 letters at 33
      cm. Five measures of autorefraction were averaged with vector analysis and both
      power in the 180 meridian and spherical equivalent was determined. Two-factor
      repeated measures analysis of variance and the mean difference and 95 per cent
      limits of agreement were calculated. RESULTS: Mean (standard deviation) lag for
      each technique was: MEM = 0.69 (0.52) D, Nott = 0.62 (0.51) D, autorefraction in
      180 = 0.66 (0.50) D and autorefraction spherical equivalent = 0.60 (0.46) D. Lag
      did not vary across techniques (p = 0.48), but children did have smaller lags
      than adults (p < 0.001) and greater amounts of uncorrected astigmatism (0.61 +/-
      0.09 D versus 0.42 +/- 0.08 D, p = 0.02). There was no significant interaction
      between age group and technique (p = 0.74). Mean differences between techniques
      were small, ranging from -0.14 to +0.06 D. Ninety-five per cent limits of
      agreement ranged from +/-0.80 to +/-1.33 around the mean with the narrowest
      ranges found for comparisons made to autorefraction in 180. Limits of agreement
      were also narrowest in children as compared to adults with similar mean
      differences between age groups. CONCLUSIONS: This study demonstrates the mean
      agreement between autorefraction and retinoscopic techniques is centred on zero
      (no bias) in both children and adults. The range of agreement becomes narrower
      when autorefraction power in the 180 is calculated, even for a sample of subjects
      with moderately small amounts of uncorrected astigmatism.

PMID- 29575033
TI  - Neurochemical abnormalities in premanifest and early spinocerebellar ataxias.
AB  - OBJECTIVE: To investigate whether early neurochemical abnormalities are
      detectable by high-field magnetic resonance spectroscopy (MRS) in individuals
      with spinocerebellar ataxias (SCAs) 1, 2, 3, and 6, including patients without
      manifestation of ataxia. METHODS: A cohort of 100 subjects (N = 18-21 in each SCA
      group, including premanifest mutation carriers; mean score on the Scale for the
      Assessment and Rating of Ataxia [SARA] <10 for all genotypes, and 22 matched
      controls) was scanned at 7 Tesla to obtain neurochemical profiles of the
      cerebellum and brainstem. A novel multivariate approach (distance-weighted
      discrimination) was used to combine regional profiles into an "MRS score."
      RESULTS: MRS scores robustly distinguished individuals with SCA from controls,
      with misclassification rates of 0% (SCA2), 2% (SCA3), 5% (SCA1), and 17% (SCA6).
      Premanifest mutation carriers with estimated disease onset within 10 years had
      MRS scores in the range of early-manifest SCA subjects. Levels of neuronal and
      glial markers significantly correlated with SARA and an Activities of Daily
      Living score in subjects with SCA. Regional neurochemical alterations were
      different between SCAs at comparable disease severity, with SCA2 displaying the
      most extensive neurochemical abnormalities, followed by SCA1, SCA3, and SCA6.
      INTERPRETATION: Neurochemical abnormalities are detectable in individuals before
      manifest disease, which may allow premanifest enrollment in future SCA trials.
      Correlations with ataxia and quality-of-life scores show that neurochemical
      levels can serve as clinically meaningful endpoints in trials. Ranking of SCA
      types by degree of neurochemical abnormalities indicates that the neurochemistry
      may reflect synaptic function or density. Ann Neurol 2018;83:816-829.

PMID- 29575035
TI  - MicroRNA expression profiles of neural stem cells following valproate inducement.
AB  - Neural stem cells (NSCs) possess self-renewal and multilineage differentiation
      ability, thus are considered to be a potential source for cell replacement
      therapy of many nervous system diseases, such as neurodegenerative diseases.
      Valproate (VPA), a member of histone deacetylase inhibitor family, is an
      epigenetic regulator and can promote NSCs to differentiate into neurons,
      nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs
      (miRNAs) exert a crucial part in the posttranscriptional regulation of gene
      expression. Epigenetic mechanisms involve in the regulation of miRNAs expression.
      Therefore we speculated that miRNAs may be important factors during the promotion
      of neuronal differentiation by VPA. Here, after selecting appropriate
      concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on
      the treatment of 1 mM VPA or vehicle. After validation, we obtained 5
      significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p,
      and miR-210-3p) in VPA group compared with control. We predicted the target genes
      of these miRNAs on the website. Through gene ontology (GO) and pathway analyses,
      we obtained preliminary comprehension of the function of these genes. The
      bioinformatics analyses indicated the involvement of them during neurogenesis. In
      addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p
      in central nervous system, which suggested that they were likely to play crucial
      roles in neuronal differentiation. We then defined the upregulation of Map2 by
      transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on
      NSCs differentiation. The present study explored the miRNAs potentially mediated
      the function of VPA on promoting NSCs to differentiate into neurons.

PMID- 29575036
TI  - The psychological distress and care needs of mesothelioma patients and asbestos
      exposed subjects: A systematic review of published studies.
AB  - BACKGROUND: The purpose of this study is to present the results of a systematic
      review of published research that focuses on psychological aspects of malignant
      mesothelioma patients and asbestos-exposed people. METHODS: Our research includes
      primary studies published between 1980 and 2016, using information from the
      Cochrane Library, the Psychology Behavioral Sciences Collection, PsychINFO,
      PubMed, PubGet, PubPsych, and Scopus, in compliance with PRISMA guidelines.
      RESULTS: We identified 12 papers that investigated the psychological distress and
      care needs of mesothelioma patients, and nine papers for asbestos-exposed
      subjects. CONCLUSIONS: This paper highlights the paucity of studies on the
      psychological distress and care needs of mesothelioma patients and asbestos
      exposed subjects. It confirms that malignant mesothelioma is associated with the
      physical, emotional, and social functioning of patients, while also suggesting
      that the risk of developing asbestos-related diseases among asbestos-exposed
      subjects is associated with high levels of psychological distress, despair, and
      mental health difficulties.

PMID- 29575037
TI  - Mechanical bacterial lysate administration prevents exacerbation in allergic
      asthmatic children-The EOLIA study.
AB  - BACKGROUND: Despite progress in asthma management, prevention of asthma
      exacerbation remains challenging in school-aged children with allergic asthma.
      New therapeutic approaches are needed. Previously, a chemical bacterial lysate
      has been successfully used in preschool children to reduce wheezing attacks. We
      assessed the effect of Polyvalent Mechanical Bacterial Lysate (PMBL(r) ) Tablet
      on asthma clinical course and control in 6- to 16-year-old children with partly
      controlled or uncontrolled allergic asthma. METHODS: A randomized, double-blind,
      placebo-controlled, parallel-group study was performed in 152 patients exhibiting
      allergic asthma assigned to receive Placebo or PMBL(r) . Eligible patients
      underwent four visits during the 9-month study. Asthma control level was assessed
      by ACT/C-ACT score. RESULTS: The main criterion was not achieved as ACT/C-ACT
      changes were similar in both groups at the end of the 3-month treatment period.
      However, the mean number (+/-SD) of asthma exacerbations was significantly lower
      with PMBL(r) Tablet than with Placebo at Week 12 (0.3 +/- 0.6 vs 0.8 +/- 1.1, P =
      .009) and over the total study period (1.1 +/- 1.3 vs 1.9 +/- 2.0, P = .01).
      Consistently, the mean number of days with exacerbation per patient was
      significantly lower with PMBL(r) Tablet (13.3 +/- 11.2 vs 19.8 +/- 15.7 over the
      whole study, P = .009). Treatment with PMBL(r) Tablet prolonged the time to
      second exacerbation by 55% (Hazard Ratio [HR]=0.45; 95% Confidence Interval [CI]
      0.27 to 0.77, P = .002) and to third exacerbation by 74% (HR=0.26; 95% CI 0.12 to
      0.58, P < .001). No serious adverse event related to PMBL(r) Tablet
      administration was recorded. CONCLUSION: Administration of PMBL(r) Tablet
      represents a safe and effective means for significantly reducing the rate of
      exacerbations in school-aged allergic asthmatic children. (EudraCT 2013-000737-12
      and NCT02541331).

PMID- 29575038
TI  - Hospital volume and short-term outcomes after cytoreductive nephrectomy.
AB  - PURPOSE: To investigate the impact of hospital volume on short-term outcomes
      after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC).
      METHODS: We identified mRCC patients who underwent CN from 2006 to 2013 in the
      National Cancer Database. Annual hospital CN volume was categorized as high (top
      20th percentile) and low. Multivariable logistic regressions were used to compare
      30-day mortality, 90-day mortality, prolonged length of stay (PLOS, >=7 days),
      and 30-day readmission rates. Sensitivity analyses were performed with hospital
      volume considered as a continuous variable. RESULTS: A total of 9789 patients
      were included with high-volume (n = 1916) defined as >=8 cases and low-volume (n
      = 7873) as 1-7 cases annually. Multivariable logistic regression showed that high
      volume was associated with lower odds of 30-day mortality (OR = 0.69, P = 0.013),
      90-day mortality (OR = 0.65, P < 0.001), PLOS (OR = 0.82, P = 0.002), and 30-day
      readmission (OR = 0.78, P = 0.028). Sensitivity analyses showed that increasing
      hospital volume (per case) was associated with lower odds of 30-day mortality (OR
      = 0.965, P = 0.008), 90-day mortality (OR = 0.966, P < 0.001), PLOS (OR = 0.982,
      P = 0.001), and 30-day readmission (OR = 0.975, P = 0.012). CONCLUSION: Higher
      hospital volume was associated with better short-term outcomes after CN. Future
      studies are needed to validate our findings and explore the potential components
      leading to better outcomes in the higher volume hospitals.

PMID- 29575039
TI  - Alopecia areata treated with hydroxychloroquine: A retrospective study of nine
      pediatric cases.
AB  - BACKGROUND/OBJECTIVES: Alopecia areata is a common hair loss condition that is
      often emotionally devastating for patients. There is a paucity of effective
      treatments available. Hydroxychloroquine has been reported as variably effective
      in inducing significant hair regrowth in adults with alopecia areata. The
      objective of this retrospective study was to assess the benefit and tolerability
      of hydroxychloroquine in pediatric alopecia areata. METHODS: We conducted a
      retrospective review of nine children with a history of alopecia areata treated
      with hydroxychloroquine. Clinical data were obtained from patients treated at two
      tertiary care centers in the United States between July 1, 2013, and July 1,
      2015. RESULTS: Alopecia scores of five patients improved by 6 months of
      treatment. Four patients experienced no improvement from baseline evaluation. The
      most common side effect associated with treatment was gastrointestinal
      intolerance and headache. CONCLUSION: This retrospective series suggests that
      hydroxychloroquine can be considered as a treatment option for alopecia areata in
      children.

PMID- 29575041
TI  - Remembering Jim Melius.

PMID- 29575040
TI  - Changes in the mitochondrial proteome of developing maize seed embryos.
AB  - Mitochondria are required for seed development, but little information is
      available about their function and role during this process. We isolated the
      mitochondria from developing maize (Zea mays L. cv. Nongda 108) embryos and
      investigated the mitochondrial membrane integrity and respiration as well as the
      mitochondrial proteome using two proteomic methods, the two-dimensional gel
      electrophoresis (2-DE) and sequential windowed acquisition of all theoretical
      fragment ion mass spectra (SWATH). Mitochondrial membrane integrity and
      respiration were maintained at a high level up to 21 days after pollination (DAP)
      and decreased thereafter, while total mitochondrial number, cytochrome c oxidase
      activity and respiration per embryo exhibited a bell-shaped change with peaks at
      35-45 DAP. A total of 286 mitochondrial proteins changed in abundance during
      embryo development. During early stages of seed development (up to 21 DAP),
      proteins involved in energy production, basic metabolism, protein import and
      folding as well as removal of reactive oxygen species dominated, while during mid
      or late stages (35-70 DAP), some stress- and detoxification-related proteins
      increased in abundance. Our study, for the first time, depicted a relatively
      comprehensive map of energy production by mitochondria during embryo development.
      The results revealed that mitochondria were very active during the early stages
      of maize embryo development, while at the late stages of development, the
      mitochondria became more quiescent, but well-protected, presumably to ensure that
      the embryo passes through maturation, drying and long-term storage. These results
      advance our understanding of seed development at the organelle level.

PMID- 29575042
TI  - Monitoring Morphologic Changes in Male Rowers Using Limited Portable
      Echocardiography Performed by a Frontline Physician.
AB  - Athletes' hearts have been studied for adaptive changes in response to exercise.
      Physiologic changes are normal responses to intense athletic training regimens,
      whereas pathologic changes predispose athletes to sudden cardiac death. The two
      alterations overlap in clinical presentation. Research continues to investigate
      the upper limits of cardiac remodeling to aid clinical decision making. Studying
      normal changes that occur in response to exercise will advance physicians'
      understanding of physiologic responses to exercise and potentially improve
      clinical distinction. To expand this body of knowledge, we present an
      observational case series that describes morphologic changes in athlete's hearts
      concurrent with performance measurements.

PMID- 29575043
TI  - Preventing family transmission of anxiety: Feasibility RCT of a brief
      intervention for parents.
AB  - OBJECTIVES: Children of anxious parents are at high risk of anxiety disorders
      themselves. The evidence suggests that this is due to environmental rather than
      genetic factors. However, we currently do little to reduce this risk of
      transmission. There is evidence that supporting parenting in those with mental
      health difficulties can ameliorate this risk. Therefore, the objective of this
      study was to test the feasibility of a new one-session, group-based, preventive
      parenting intervention for parents with anxiety disorders. DESIGN: Feasibility
      Randomized Controlled Trial. METHODS: A total of 100 parents with anxiety
      disorders, recruited from adult mental health services in England (and child aged
      3-9 years), were randomized to receive the new intervention (a 1-day, group
      workshop), or to treatment as usual. Children's anxiety disorder and anxiety
      symptoms were assessed to 12 months by outcome assessors who were blind to group
      allocation. Exploratory analyses were conducted on an intention to treat basis,
      as far as possible. RESULTS: A total of 51 participants were randomized to the
      intervention condition and 49 to the control condition (82% and 80% followed to
      12 months, respectively). The attendance rate was 59%, and the intervention was
      highly acceptable to parents who received it. The RCT was feasible, and 12-month
      follow-up attrition rates were low. Children whose parents were in the control
      condition were 16.5% more likely to have an anxiety disorder at follow-up than
      those in the intervention group. No adverse events were reported. CONCLUSIONS: An
      inexpensive, light-touch, psycho-educational intervention may be useful in
      breaking the intergenerational cycle of transmission of anxiety disorders. A
      substantive trial is warranted. PRACTITIONER POINTS: Anxiety disorders run in
      families, but we currently do little to help anxious parents to raise confident
      children. A brief group workshop was highly acceptable to such parents and was
      very inexpensive to run. Children of parents who took part in the brief
      intervention were 16.5% less likely to have an anxiety disorder, 1 year later,
      than children whose parents were in the control group. This was a feasibility
      study, and while it showed that both the intervention and the research were
      feasible, the study needs replicating with a much larger sample. Many parents
      faced barriers to attending the workshop, and future efforts should focus on
      widening accessibility. We were unable to obtain sufficient self-report data from
      children, so the outcomes are based on parent report only.

PMID- 29575044
TI  - Correlation between neutrophil/lymphocyte ratio and Ranson score in acute
      pancreatitis.
AB  - BACKGROUND: Acute pancreatitis (AP) is characterized by inflammation of the
      pancreas, elevated pancreatic enzymes, and abdominal pain. The neutrophil to
      lymphocyte ratio (NLR) is used as a marker of inflammation. In this retrospective
      study, we aimed to investigate novel early prognostic predictors of AP, such as
      NLR and its correlation with the Ranson score. METHODS: A total 435 patients
      (Male: 152; 34.9%, Age: 63.53 +/- 17.22 years) were included in the study. Data
      were collected by two clinicians scanning the registered hospital records.
      RESULTS: Classification of the patients according to the aetiologies revealed
      gallstone(s) 58.6% (n = 255), hyperlipidaemia 2.2% (n = 9), viruses 0.7% (n = 3),
      malignancies 0.5% (n = 2), and alcohol 0.2% (n = 1). No reason was discovered in
      37.9% (n = 165) of patients. Age, duration in the intensive care unit, serum
      aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT), alkaline
      phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, direct
      bilirubin, lactate dehydrogenase (LDH), white blood cell (WBC) count, neutrophil
      count, lymphocyte count, and the NLR were greater in the group with a Ranson
      score >=3 than the group with a Ranson score <3. DISCUSSION: Quick diagnosis is
      essential in AP. Current scoring systems for AP diagnosis are complicated,
      whereas NLP is a simple, practical, and effective marker.

PMID- 29575045
TI  - Synthesis, anticancer activity, and molecular modeling of etodolac-thioether
      derivatives as potent methionine aminopeptidase (type II) inhibitors.
AB  - A series of (R,S)-1-{[5-(substituted)sulfanyl-4-substituted-4H-1,2,4-triazole-3
      yl]methyl}-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indoles (5a-v) were
      designed and synthesized using a five-step synthetic protocol that involves
      substituted benzyl chlorides and (R,S)-5-[(1,8-diethyl-1,3,4,9
      tetrahydropyrano[3,4-b]indole-1-yl)methyl]-4-substituted-2,4-dihydro-3H-1,2,4
      triazole-3-thiones in the final step. The synthesized derivatives were evaluated
      for cytotoxicity and anticancer activity in vitro using the MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric method
      against VERO, HEPG2 (human hepatocellular liver carcinoma), SKOV3 (ovarian
      carcinoma), MCF7 (human breast adenocarcinoma), PC3 and DU145 (prostate
      carcinoma) cells at 10-5  M (10 MUM) for 24 h. Compounds 5d and 5h showed the
      best biological potency against the SKOV3 cancer cell line (IC50  = 7.22 and 5.10
      MUM, respectively) and did not display cytotoxicity toward VERO cells compared to
      etodolac. Compounds 5k, 5s, and 5v showed the most potent biological activity
      against the PC3 cancer cell line (IC50  = 8.18, 3.10, and 4.00 MUM, respectively)
      and did not display cytotoxicity. Moreover, these compounds were evaluated for
      caspase-3, -9, and -8 protein expression and activation in the apoptosis pathway
      for 6, 12, and 24 h, which play a key role in the treatment of cancer. In this
      study, we also investigated the apoptotic mechanism and molecular modeling of
      compounds 5k and 5v on the methionine aminopeptidase (type II) enzyme active site
      in order to get insights into the binding mode and energy.

PMID- 29575046
TI  - Enhancing integration of articular cartilage grafts via photochemical bonding.
AB  - The integration of osteochondral grafts to native articular cartilage is critical
      as the lack of graft integration may lead to continued tissue degradation, poor
      load transfer and inadequate nutrient transport. Photochemical bonding promotes
      graft integration by activating a photosensitizer at the interface via a light
      source and avoids negative effects associated with other bonding techniques. We
      hypothesized that the bond strength depends on photosensitizer type and
      concentration in addition to light exposure. Photochemical bonding was evaluated
      using methylene blue (MB), a cationic phenothiazine photosensitizer, and two
      phthalocyanine photosensitizers, Al(III) phthalocyanine chloride tetrasulfonic
      acid (CASPc) and aluminum phthalocyanine chloride (AlPc). Exposure was altered by
      varying irradiation time for a fixed irradiance or by varying irradiance with a
      fixed irradiation time. MB was ineffective at producing bonding at the range of
      concentrations tested while CASPc produced a peak twofold bond strength increase
      over controls. AlPc produced substantial bonding at all concentrations with a
      peak 3.9-fold bond strength increase over controls. Parametric tests revealed
      that bond strength depended primarily on the total energy delivered to the
      bonding site rather than the rate of light delivery or light irradiance. Bond
      strength persisted for 1 week of in-vitro culture, which warrants further
      exploration for clinical applications. These studies indicate that photochemical
      bonding is a viable strategy for enhancing articular cartilage graft integration.
      (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res 36:2406-2415, 2018.

PMID- 29575048
TI  - Advancing the Science of Self-Management in Adults With Long-Term Left
      Ventricular Assist Devices.
AB  - This study tested the applicability of the individual and family self-management
      theory (IFSMT) to self-management (SM) in patients with left ventricular assist
      devices (LVADs). From an existing data set, we extracted the following variables
      that correspond to IFSMT's conceptual dimensions: anxiety, depression, and
      cognition (context dimension); self-efficacy (SM process dimension); adherence
      and quality of life (QOL; outcome dimensions). Descriptive statistics and partial
      least squares path modeling procedures were used for data analyses. A total of
      100 patients (mean age 52 +/- 13.4 years) with continuous flow LVAD designs
      comprised the present study. Most patients were White (78%), married (69%),
      college-educated (72%), and on disability (53%). Their mean anxiety and
      depression scores were slightly above normal, while their cognitive function
      scores were slightly lower than normal. LVAD care self-efficacy, adherence, and
      QOL were within normal ranges. Factor loadings ranged from 0.50 to 1.0, and there
      were significant forward path relationships among the context, process, and
      outcome dimensions (beta ranges from 0.02 to 0.60, all P values < 0.05). In
      conclusion, the IFSMT provides a good fit for SM in LVAD. Further research is
      needed to clarify how best to improve LVAD SM practice and treatment outcomes.

PMID- 29575047
TI  - Assessment of MR-based R2* and quantitative susceptibility mapping for the
      quantification of liver iron concentration in a mouse model at 7T.
AB  - PURPOSE: To assess the feasibility of quantifying liver iron concentration (LIC)
      using R2* and quantitative susceptibility mapping (QSM) at a high field strength
      of 7 Tesla (T). METHODS: Five different concentrations of Fe-dextran were
      injected into 12 mice to produce various degrees of liver iron overload. After
      mice were sacrificed, blood and liver samples were harvested. Ferritin enzyme
      linked immunosorbent assay (ELISA) and inductively coupled plasma mass
      spectrometry were performed to quantify serum ferritin concentration and LIC.
      Multiecho gradient echo MRI was conducted to estimate R2* and the magnetic
      susceptibility of each liver sample through complex nonlinear least squares
      fitting and a morphology enabled dipole inversion method, respectively. RESULTS:
      Average estimates of serum ferritin concentration, LIC, R2*, and susceptibility
      all show good linear correlations with injected Fe-dextran concentration;
      however, the standard deviations in the estimates of R2* and susceptibility
      increase with injected Fe-dextran concentration. Both R2* and susceptibility
      measurements also show good linear correlations with LIC (R2  = 0.78 and R2  =
      0.91, respectively), and a susceptibility-to-LIC conversion factor of 0.829
      ppm/(mg/g wet) is derived. CONCLUSION: The feasibility of quantifying LIC using
      MR-based  R2* and QSM at a high field strength of 7T is demonstrated.
      Susceptibility quantification, which is an intrinsic property of tissues and
      benefits from being field-strength independent, is more robust than R2*
      quantification in this ex vivo study. A susceptibility-to-LIC conversion factor
      is presented that agrees relatively well with previously published QSM derived
      results obtained at 1.5T and 3T.

PMID- 29575049
TI  - Molecular detection of fungi of public health importance in wild animals from
      Southern Brazil.
AB  - Some animals have an important relationship with fungal infections, and searching
      for pathogens in animal samples may be an opportunity for eco-epidemiological
      research. Since studies involving wildlife are generally restricted, using
      samples from road kills is an alternative. The aim of this study was to verify
      whether pathogenic fungi of public health importance occur in wildlife road kills
      from Santa Catarina State, Brazil. Organ samples (n = 1063) from 297 animals were
      analysed according to Polymerase Chain Reaction (PCR) using universal primers to
      detect fungi in general and, subsequently, using primers specific to
      Paracoccidioides brasiliensis, Histoplasma capsulatum and Cryptococcus spp. There
      were 102 samples positive for fungal species. Eight samples were positive for P.
      brasiliensis, three samples were positive for Cryptococcus spp. and one sample
      had coinfection by these two fungi. No sample was positive for Histoplasma spp.
      according to the molecular detection. Genetic sequencing allowed the
      identification of Fungal sp. in 89 samples, Cryptococcus neoformans in two
      samples and Aspergillus penicillioides in three samples. This study shows the
      importance of wild animals in the epidemiology of fungal infections and assists
      in the mapping of pathogen occurrence in a region that was not previously
      evaluated.

PMID- 29575050
TI  - Impact of HIV infection and highly active antiretroviral therapy (HAART) on B
      cell subpopulations in children.
AB  - B-cells play an important role in defending children against various infections.
      In view of scare data, we undertook this prospective cohort study to describe B
      cell compartment in HIV infected children (<5 years of age) and the effect of
      HAART on B cell subpopulations. HIV infected children (<5 years) from Pediatric
      HIV services of the Department of Pediatrics, All India Institute of Medical
      Sciences, New Delhi, were recruited (April 2012-December 2015). The enrolled HIV
      1 infected children (n = 59) were followed up regularly for 12 months; healthy
      controls (n = 51) included HIV uninfected children with no major illness. Flow
      cytometry was performed on fresh EDTA-treated blood samples to characterize B
      cell subpopulations. In HIV-infected children, marked depletion of naive (P =
      0.003), non-switched memory (P = 0.02), mature (P = 0.0005), resting memory (P <
      0.0001) B cells, and expansion of double negative memory (P < 0.0001), activated
      memory (P < 0.0001) and tissue like memory (P < 0.0001) B cells were observed as
      compared to healthy controls. In children started on HAART, at the end of 12
      months of therapy, frequencies of non-switched memory (P = 0.04), switched memory
      (P = 0.01), and resting memory (P = 0.003) B cells were lower; activated memory
      (P = 0.04), and tissue-like memory (P = 0.0001) B cells were still higher than
      healthy controls. HIV infection resulted in reduced memory B cells in HIV
      infected children. Following HAART, there was normalization of some B cell
      subpopulations. The study emphasizes the need of re-vaccination in HIV infected
      children to maintain the memory B cell pool and adequate humoral immune response
      against infections.

PMID- 29575051
TI  - Relationships between dysphagia and tongue pressure during swallowing in
      Parkinson's disease patients.
AB  - Although dysphagia is a life-threatening problem in patients with Parkinson's
      disease (PD), the pathophysiology of oropharyngeal dysphagia is yet to be
      understood. This study investigated the tongue motor function during swallowing
      in relation to dysphagia and the severity of PD. Thirty patients with PD (14
      males and 16 females; average age, 69.4 years), Hoehn and Yahr stage II-IV, in
      Osaka University Hospital are participated in this study. During swallowing 5 ml
      of water, tongue pressure on the hard palate was measured using a sensor sheet
      with 5 measuring points. The maximal tongue pressure at each measuring point
      during swallowing was compared between patients with PD and healthy controls.
      Subjective assessment of oropharyngeal dysphagia was performed using Swallowing
      Disturbance Questionnaire-Japanese. The maximal tongue pressure at each measuring
      point was significantly lower in patients with PD than in healthy controls (8
      males and 12 females; average age, 71.6 years). Furthermore, the maximal tongue
      pressure was significantly lower in dysphagic PD patients than non-dysphagic PD
      patients. Loss of tongue pressure production at the anterior part of the hard
      palate was strongly related to dysphagia in the oral phase as well as in the
      pharyngeal phase. An abnormal pattern of tongue pressure production was more
      frequently observed in dysphagic PD patients than in non-dysphagic PD patients.
      The results suggest that tongue pressure measurement might be useful for early
      and quantitative detection of tongue motor disability during swallowing in
      patients with PD.

PMID- 29575052
TI  - Expression profile of pattern recognition receptors in skeletal muscle of
      SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.
AB  - AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of
      motoneurons and progressive muscle wasting. Inflammatory processes, mediated by
      non-neuronal cells, such as glial cells, are known to contribute to disease
      progression. Inflammasomes consist of pattern recognition receptors (PRRs),
      apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for
      interleukin (IL) processing and a rapid immune response after tissue damage.
      Recently, we described inflammasome activation in the spinal cord of ALS patients
      and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are
      early events in ALS, we hypothesized that PRRs might be abnormally expressed in
      muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and
      immunohistochemistry were performed with muscle tissue from presymptomatic and
      early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and
      sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding
      oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3
      (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2.
      Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1beta)
      and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was
      detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1beta were
      significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients.
      Furthermore, levels of caspase 1 and IL1beta were already increased in
      presymptomatic animals. CONCLUSION: Our findings suggest that increased
      inflammasome activation may be involved in skeletal muscle pathology in ALS.
      Furthermore, elevated levels of NLRC4, caspase 1 and IL1beta reflect early
      changes in the skeletal muscle and may contribute to the denervation process.

PMID- 29575053
TI  - Captive chimpanzee (Pan troglodytes) behavior as a function of space per animal
      and enclosure type.
AB  - Space per animal, or animal density, and enclosure type are important elements of
      functionally appropriate captive environments (FACEs) for chimpanzees. The
      National Institutes of Health (NIH) recommends that captive chimpanzees be
      maintained in areas of >250 ft2 /animal. Several studies have investigated
      chimpanzee behavior in relation to space per animal, but only two studies have
      examined these variables while attempting to hold environmental complexity
      constant. Both have found few, if any, significant differences in behavior
      associated with increased space per animal. The NIH does not provide
      recommendations pertaining to enclosure type. Although PrimadomesTM and corrals
      are considered acceptable FACE housing, no studies have investigated chimpanzee
      behavior in relation to these two common types of enclosures. We examined the NIH
      space per animal recommendation, and the effects of enclosure type, while
      maintaining similar levels of environmental complexity. We used focal animal
      observations to record the behavior of 22 chimpanzees in three social groups
      following within-facility housing transfers. Chimpanzees that were moved from an
      area with space below the NIH recommendation to the same type of enclosure with
      space above the recommendation (dome to double dome) exhibited significantly more
      locomotion and behavioral diversity post-transfer. Chimpanzees that were moved
      from an area with space below the recommendation to a different type of enclosure
      with space above the recommendation (dome to corral) exhibited significant
      increases in foraging and behavioral diversity, and a decrease in rough
      scratching. Lastly, chimpanzees that were moved from an area above the
      recommendation to a different enclosure type with space equal to the
      recommendation (corral to double dome) exhibited an increase in behavioral
      diversity. These results add to the body of literature that addresses the concept
      of specific minimum space requirements per chimpanzee, and highlight the need for
      more empirical investigation of the relationship between space per chimpanzee,
      behavior, and welfare.

PMID- 29575054
TI  - Living together: Malaria and filaria.

PMID- 29575055
TI  - MicroRNA-190b regulates lipid metabolism and insulin sensitivity by targeting IGF
      1 and ADAMTS9 in non-alcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by ectopic lipid
      accumulation and insulin resistance, yet the underlying molecular mechanisms are
      poorly understood. MiR-190b is thought to play a role in hepatocellular carcinoma
      by modulating insulin resistance; however, its role in NAFLD remains unknown.
      Here, we found that miR-190b expression was significantly increased in the liver
      tissues of patients with NAFLD, compared to normal tissues. Moreover, miR-190b
      was upregulated in a high-fat diet NAFLD mouse model and a free fatty acid
      induced NAFLD cellular model. Knockdown of miR-190b decreased aspartate
      transaminase (AST), alanine transaminase (ALT), triglyceride (TG), and total
      cholesterol (TC). It also reduced expression of the lipogenic genes fatty acid
      synthase (FAS) and 3-hydroxy-3-methylglutarylCoA reductase (HMGCR), alleviated
      hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and
      activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in
      vitro. Furthermore, we confirmed that miR-190b directly targeted IGF-1 and
      ADAMTS9. MiR-190b overexpression suppressed expression of IGF-1 and ADAMTS9,
      which were increased by miR-190b inhibition. Expression of IGF-1 and ADAMTS9 was
      inversely correlated with miR-190b in liver tissues of patients with NAFLD,
      respectively. We also found that IGF-1 or ADAMTS9 inhibition partially reversed
      the effects of miR-190b on lipid metabolism and insulin signaling in vitro. Taken
      together, the data reveal that miR-190b inhibition suppressed lipid accumulation
      and improved insulin sensitivity by targeting IGF-1 and ADAMTS9, suggesting that
      miR-190b inhibition may be a therapeutic strategy against NAFLD.

PMID- 29575056
TI  - Subgroup analysis with semiparametric models toward precision medicine.
AB  - In analyzing clinical trials, one important objective is to classify the patients
      into treatment-favorable and nonfavorable subgroups. Existing parametric methods
      are not robust, and the commonly used classification rules ignore the fact that
      the implications of treatment-favorable and nonfavorable subgroups can be
      different. To address these issues, we propose a semiparametric model,
      incorporating both our knowledge and uncertainty about the true model. The Wald
      statistics is used to test the existence of subgroups, while the Neyman-Pearson
      rule to classify each subject. Asymptotic properties are derived, simulation
      studies are conducted to evaluate the performance of the method, and then method
      is used to analyze a real-world trial data.

PMID- 29575057
TI  - Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired
      during obesity by endoplasmic reticulum stress.
AB  - Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as
      triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation
      and lipotoxicity. During obesity, an impairment in the capacity of SAT to store
      triglycerides and synthesize adiponectin is associated with increased free fatty
      acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle
      lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response
      (UPR) may be involved in SAT dysfunction during obesity. The objectives of this
      study were to assess UPR activation and adiponectin synthesis in: 1) SAT and VAT
      from mice exposed to acute pharmacologic or chronic obesity-induced ER stress and
      in 2) cultured mice primary mature adipocytes or adipocytes differentiated in
      vitro from SAT and VAT exposed to tunicamycin or thapsigargin. Mice fed a high
      fat diet developed obesity, increased FFA and lower circulating adiponectin in
      association with lower adiponectin synthesis and increased UPR markers in SAT.
      Mice subjected to acute ER stress by pioglitazone administration and a low-dose
      tunicamycin injection presented a maladaptive UPR activation in SAT along with
      reduced adiponectin synthesis and secretion and increased lipolysis with respect
      to VAT, associated with lipid accumulation in skeletal muscle and liver. Primary
      adipocytes and adipocytes differentiated from SAT exposed to pharmacologic ER
      stress also developed maladaptive UPR, along with reduced adiponectin synthesis
      and increased lipolysis with respect to those from VAT. Our results indicate that
      compared to VAT, SAT is more susceptible to ER stress, leading to increased
      lipolysis and reduced adiponectin synthesis and secretion.

PMID- 29575058
TI  - Amino acids as chiral derivatizing agents for antiproliferative substituted N
      benzyl isoindolinones.
AB  - The absolute configurations of the diastereomers of novel amino acid ester
      derivatives of 2,3-substituted isoindolinones, which are known as apoptosis
      activators due to their ability to inhibit the MDM2-p53 PPI, were assigned using
      NMR and computational methods. Procedures for diastereomer separation and
      determining the absolute configuration were developed to perform the study. The
      high significance of N-benzyl fragment for the determination of the diastereomer
      absolute configuration by NMR methods was established; it is determined by a
      number of factors inherent in this fragment and the structural features of the
      studied substrates. Analysis of the individual isomer activity showed that the
      target inhibitory effect of S- and R-isoindolinone L-valinates differs by less
      than 20%. It can be explained by the presence of a flexible linker between the
      isoindolinone core and amino acid fragment, which provides the optimal
      arrangement of the molecule in the hydrophobic cavity of MDM2 for both isomers.

PMID- 29575059
TI  - Simultaneous measurement of glutamate, glutamine, GABA, and glutathione by
      spectral editing without subtraction.
AB  - PURPOSE: To simultaneously measure glutamate, glutamine, gamma-aminobutyric acid
      (GABA), and glutathione using spectral editing without subtraction at 7T.
      METHODS: A novel spectral editing approach was proposed to simultaneously measure
      glutamate, glutamine, GABA, and glutathione using a TE of 56 ms at 7T. By
      numerical optimization of sequence timing in the presence of an editing pulse,
      the 4 metabolites all form relatively intense pseudo singlets with maximized peak
      amplitudes and minimized peak linewidths in 1 of the 3 interleaved spectra. For
      measuring glutamate, glutamine, and glutathione, the editing pulse targets the H3
      protons of these metabolites near 2.12 parts per million. Both GABA H2 and H4
      resonances are fully utilized in spectral fitting. RESULTS: Concentration levels
      (/[total creatine]) of glutamate, glutamine, GABA, and glutathione from an 8 mL
      voxel in the pregenual anterior cingulate cortex of 5 healthy volunteers were
      found to be 1.26 +/- 0.13, 0.33 +/- 0.06, 0.13 +/- 0.03, and 0.27 +/- 0.03,
      respectively, with within-subject coefficient of variation at 3.2%, 8.2%, 7.1%,
      and 10.2%, respectively. The total scan time was less than 4.5 min. CONCLUSIONS:
      The proposed new technique does not require data subtraction. The 3 major
      metabolites of the glutamatergic and GABAergic systems and the oxidative stress
      marker glutathione were all measured in 1 short scan with high precision.

PMID- 29575060
TI  - Real-life 3D therapy failure: Analysis of NS5A 93H RAS plus 108 K polymorphism in
      complex with ombitasvir by molecular modeling.
AB  - We report a real-life 3D therapy failure in a patient treated with ombitasvir
      (OMV)/paritaprevir/ritonavir and dasabuvir without ribavirin (3D-R). He had
      therapy failure at week 12 after the end of treatment. We detected resistance
      associated substitutions (RASs) plus polymorphisms on NS3, NS5A, and NS5B target
      regions by population sequencing (15% cut-off) at baseline, at relapse and during
      follow-up. About this, NS5A RASs generally persist longer than resistances in the
      other target genes and may impact treatment outcome. Therefore, to evaluate OMV
      drug-resistance mechanism, we studied the acquired RAS plus polymorphisms on NS5A
      phosphoprotein by computational studies. OMV showed a higher affinity towards
      baseline and 93H/108 K mutant structure (follow-up) with respect to 93H/R108
      mutant structure (relapse) on phosphoprotein. By Molecular Dynamics simulations
      (MDs), structural information about the protein stability in presence of OMV were
      observed. According to our data, molecular modeling approach has proved to be a
      powerful method to evaluate the impact of these RASs plus specific amino acid
      (AA) changes on phosphoprotein.

PMID- 29575062
TI  - Restored response to ADP downstream of purinergic P2Y12 receptor in apheresis
      platelets after pathogen-reducing xenon flash treatment.
AB  - BACKGROUND: Our previous study revealed that pathogen-reducing filtered xenon
      flash-treated platelets (fXe-PLTs) showed sustained aggregation in response to
      adenosine diphosphate (ADP), but apheresis-collected PLTs (Aph-PLTs) showed
      reversible aggregation. STUDY DESIGN AND METHODS: Aph-PLTs, fXe-PLTs, and freshly
      prepared PLTs (PRP-PLTs) from whole blood were used to investigate the following
      responses to ADP: concentration response and effects of ADP receptor antagonists
      on aggregation, the cytosolic calcium (Ca2+ ) flux downstream of P2Y1 receptor
      signaling, and phosphorylation of vasodilator-stimulated phosphoprotein (VASP)
      and signaling intermediate protein Akt downstream of the P2Y12 receptor. RESULTS:
      The aggregation of Aph-PLTs by ADP (10 uM) changed from reversible to sustained
      in an fXe flash dose-dependent manner. The concentration-response curve of Aph
      PLTs showed a fivefold higher 50% effective concentration compared with PRP-PLTs,
      and fXe treatment decreased it to threefold. While the basal Ca2+ level was
      higher both in Aph- and fXe-PLTs than in PRP-PLTs, the increase of cytosolic Ca2+
      by ADP remained unchanged in Aph- and PRP-PLTs, but was slightly reduced in fXe
      PLTs. Although the forskolin-induced VASP phosphorylation was significantly
      reduced in Aph-PLTs, and partially restored by the fXe treatment, ADP stimulation
      attenuated this phosphorylation to an equivalent extent among the three PLT
      types. The ADP-stimulated time-dependent Akt phosphorylation was weak in Aph
      PLTs, whereas fXe-PLTs and PRP-PLTs showed a marked increase. CONCLUSION: These
      results indicate that the reversible aggregation of Aph-PLTs is the consequence
      of insufficient Akt phosphorylation. The fXe treatment restores the increase of
      phosphorylated Akt, resulting in the sustained aggregation of fXe-PLTs similar to
      those of PRP-PLTs.

PMID- 29575061
TI  - Association between site-specific bone mineral density and glucose homeostasis
      and anthropometric traits in healthy men and women.
AB  - OBJECTIVE: Patients with type 2 diabetes mellitus have an increased risk of
      fracture despite normal or increased bone mineral density (BMD). Studies on the
      relationship of glucose homeostasis with BMD phenotypes have been inconclusive
      because distinguishing the roles of insulin resistance and hyperglycaemia in bone
      remodelling is challenging. In this study, we sought to define the relationship
      of site-specific BMD with glucose homeostasis traits and anthropometric traits.
      DESIGN/PATIENTS/MEASUREMENTS: In a cross-sectional study, we examined 787
      subjects from the Mexican-American Coronary Artery Disease (MACAD) cohort who had
      undergone euglycaemic-hyperinsulinaemic clamps, oral glucose tolerance testing
      and dual X-ray absorptiometry. Glucose homeostasis traits included insulinogenic
      index (IGI30), insulin sensitivity (M value), insulin clearance (MCRI), fasting
      insulin, fasting glucose and 2-hour glucose. Univariate and multivariate analyses
      were performed to assess the association of glucose homeostasis and
      anthropometric traits with site-specific BMD. RESULTS: Two-hour glucose was
      negatively associated with arm BMD in women, which remained significant in
      multivariate analysis (beta = -.15, P = .0015). Positive correlations between
      fasting insulin and BMD at weight-bearing sites, including pelvis (beta = .22, P
      < .0001) and legs (beta = .17, P = .001) in women and pelvis (beta = .33, P <
      .0001) in men, lost significance after multivariate adjustment. Lean mass
      exhibited strong independent positive associations with BMD at multiple sites in
      both sexes. CONCLUSION: Our findings suggest that (i) anabolic effects of insulin
      might work via mechanical loading from lean mass; (ii) a direct negative effect
      of increasing glucose might be more prominent at cortical-bone-rich sites in
      women; and (iii) lean mass is a strong positive predictor of bone mass.

PMID- 29575063
TI  - A predominantly glial origin of axonal ribosomes after nerve injury.
AB  - Axonal mRNA transport and local protein synthesis are crucial for peripheral axon
      regeneration. To date, it remains unclear how ribosomes localize to axons. They
      may be co-transported with mRNAs or, as suggested by recent studies, transferred
      from Schwann cells (SC). Here, we generated transgenic "RiboTracker" mice
      expressing tdTomato-tagged ribosomal protein L4 in specific cell types when
      crossed with Cre lines. Two neuronal RiboTracker-Cre lines displayed extremely
      low levels of axonal L4-tdTomato-positive ribosomes. In contrast, two glial
      RiboTracker-Cre lines revealed tagged ribosomes in sciatic nerve (SN) axons with
      increasing amounts after injury. Furthermore, non-RiboTracker dorsal root ganglia
      co-cultured with L4-tdTomato-expressing SCs displayed tagged ribosomes in axons.
      These data provide unequivocal evidence that SN axons receive ribosomes from SCs
      upon injury and indicate that glial cells are the main source of axonal
      ribosomes.

PMID- 29575064
TI  - Continuing medical education activities for improved management of allergy
      patients.

PMID- 29575065
TI  - Evidence for the role of INSL3 on sperm production in boars by passive
      immunisation.
AB  - Insulin-like factor 3 (INSL3), previously called relaxin-like factor, is
      essential for foetal testis descent and has been implicated in sperm production
      in adult males. This study investigated the role of INSL3 in sperm production by
      examining the effect of neutralising INSL3 by passive immunisation on testicular
      function and sperm output in boars. Six male Duroc boars were randomly assigned
      to passive immunisation and control groups (n = 3 each). The immunisation group
      was intravenously injected with an IgG fraction of anti-INSL3 antibody developed
      against the B domain of INSL3 at 2-week intervals from 21-40 weeks of age. The
      control group was treated with normal IgG in the same manner. Antibody
      administration reduced testis weight and caused a fourfold increase in the
      frequency of apoptotic germ cells, which was associated with upregulation of the
      pro-apoptotic caspase 3 and BAX, and downregulation of the anti-apoptotic XIAP
      and BCL2, and a substantial marked reduction in sperm concentration. Neutralising
      INSL3 delivered by passive immunisation reduced testis weight and sperm
      concentration by inducing germ cell apoptosis, suggesting that INSL3 acts as a
      germ cell survival/anti-apoptotic factor in the maintenance of sperm production.

PMID- 29575066
TI  - High speed ink aggregates are ejected from tattoos during Q-switched Nd:YAG laser
      treatments.
AB  - INTRODUCTION: Dark material has been observed embedded within glass slides
      following Q-switched Nd:YAG laser treatment of tattoos. It appears that these
      fragments are ejected at high speed from the skin during the treatment. METHOD:
      Light microscopic analysis of the slides reveals aggregates of dark fragmented
      material, presumably tattoo ink, with evidence of fractured/melted glass.
      Photomicrographs reveal that the sizes of these aggregates are in the range 12
      MUm to 0.5 mm. RESULTS: Tattoo ink fragments were clearly observed on the surface
      and embedded within glass slides. Surface aggregates were observed as a fine dust
      and were easily washed off while deeper fragments remained in situ. The embedded
      fragments were not visible to the unaided eye. Some fragments appeared to have
      melted yielding an "insect-like" appearance. These were found to be located
      between approximately 0.2 and 1 mm deep in the glass. CONCLUSION: Given the
      particle masses and kinetic energies attained by some of these aggregates their
      velocities, when leaving the skin, may be hundreds to thousands of metres per
      second. However, the masses of the aggregates are minuscule meaning that laser
      operators may be subjected to these high-speed aggregates without their
      knowledge. These high-speed fragments of ink may pose a contamination risk to
      laser operators. Lasers Surg. Med. 9999:1-7, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29575067
TI  - White spiky papules on face of a 6 year old child.

PMID- 29575068
TI  - Imiquimod cream for molluscum contagiosum: Neither safe nor effective.

PMID- 29575069
TI  - Diffuse pityriasiform eruption in a pediatric patient after bone marrow
      transplantation.

PMID- 29575070
TI  - Pruritic reticulated eruption.

PMID- 29575071
TI  - Skin lesions and constitutional syndrome in a female adolescent.

PMID- 29575072
TI  - Comment on "Molluscum contagiosum: Review and update on management".

PMID- 29575073
TI  - Patient Perspectives: What is a pyogenic granuloma?

PMID- 29575074
TI  - Comment on "Bumps in the Road: Panniculitis in Children and Adolescents Treated
      with Vemurafenib".

PMID- 29575075
TI  - Adverse events reported to the Food and Drug Administration from 2004 to 2016 for
      cosmetics and personal care products marketed to newborns and infants.
AB  - BACKGROUND/OBJECTIVES: Despite their ubiquitous use and several recent health
      controversies involving cosmetics and personal care products for children, the
      Food and Drug Administration has little oversight of these products and relies on
      consumer-submitted adverse event reports. We assessed the recently released
      Center for Food Safety and Applied Nutrition's Adverse Event Reporting System
      database for adverse event reports submitted to the Food and Drug Administration
      for baby personal care products and to determine whether useful insights can be
      derived. METHODS: We extracted the Center for Food Safety and Applied Nutrition's
      Adverse Event Reporting System data file from 2004 to 2016 and examined the
      subset classified according to the Food and Drug Administration-designated
      product class as a baby product. Events were manually categorized into product
      type and symptom type to assess for trends. RESULTS: Only 166 total adverse
      events were reported to the Food and Drug Administration for baby products from
      2004 to 2016. The majority of reports indicated rash or other skin reaction; 46%
      of reported events led to a health care visit. CONCLUSION: Pediatric
      dermatologists should consider submitting cosmetics and personal care product
      adverse event reports and encouraging consumers to do so likewise in situations
      in which a product adversely affects a child's health.

PMID- 29575076
TI  - White scarlike lesions in a female infant with bilious emesis and sixth nerve
      palsy.

PMID- 29575077
TI  - Interferon-alpha induced psoriasis in a teenager.
AB  - Exacerbation of preexisting and development of new-onset psoriasis have been
      reported secondary to interferon treatment and, more recently, with newer
      biologic agents. We report a case of interferon-induced psoriasis in an
      adolescent with hepatitis C, a rarely reported medication reaction in children.
      This case highlights the importance of reviewing a patient's medication list when
      evaluating cutaneous disorders.

PMID- 29575078
TI  - Comment on "Congenital Lupus with Multiorgan Involvement: A Case Report and
      Review of Literature".

PMID- 29575079
TI  - Curvilinear, erythematous plantar patch in a toddler.

PMID- 29575080
TI  - Comment on "Scabies in babies".

PMID- 29575081
TI  - Expression profiling of planarians shed light on a dual role of programmed cell
      death during the regeneration.
AB  - Most animals hold the ability to regenerate damaged cells, tissues, and even any
      lost part of their bodies. To date, there is little known about the precise
      regulatory mechanism of regeneration and many fundamental questions remain
      unanswered. To further understand the precise regulatory mechanism of
      regeneration, we used planarian Dugesia japonica as a model and sequenced the
      transcriptomes of their regenerated tissues at different regeneration stages.
      Through de novo assembly and expression profiling, we found that Heat shock
      protein and MAPK pathway were involved into early response of regeneration in D.
      japonica. In addition, immune response, cell proliferation, and migration were
      activated during regeneration. Of notes, our results revealed a specific
      functional role of programmed cell death (PCD) in regeneration of D. japonica.
      PCD may not only remove the damaged and superfluous tissues for further
      patterning with regenerated tissues, but also provide signals to trigger
      neoblasts proliferation and differentiation directly. Together, our results
      revealed Heat shock protein and MAPK pathway mediated early response of
      regeneration and found a dual role of PCD in regeneration D. japonica. Meanwhile,
      we constructed regulatory networks of apoptosis, autophagy, and related signaling
      pathways and proposed a schematic model, which provided a global landscape of
      regeneration.

PMID- 29575082
TI  - Somatic sprouts of the Purkinje cells in a patient with multiple system atrophy.
AB  - We describe the post mortem case of a 71-year-old Japanese woman diagnosed as
      having multiple system atrophy (MSA), showing somatic sprouting formation of
      Purkinje cells. The patient had suffered from frequent falling episodes and
      clumsiness of the left hand since the age of 67 years. Orthostatic hypotension
      and parkinsonism subsequently emerged. Typical neuropathological features of MSA,
      including degeneration of the striatum, pontine base and cerebellum with
      abundance of phosphorylated alpha-synuclein-positive neuronal and glial
      cytoplasmic and nuclear inclusions in the brain, were observed. In addition to
      gliosis of the cerebellar white matter and notable loss of Purkinje cells,
      several Purkinje cells showed somatic sprouting. Somatic sprouting of Purkinje
      cells has been demonstrated in several specific conditions, such as developing
      brains and several neurodegenerative disorders, including Menkes kinky hair
      disease, familial spinocerebellar ataxia, acute encephalopathy linked to familial
      hemiplegic migraine, and Huntington's disease; however, no MSA cases have been
      reported with sprouting from the soma of Purkinje cells. Axonal damage caused by
      oligodendroglial dysfunction could be crucial in the development of Purkinje cell
      loss in MSA. Moreover, no apparent alpha-synuclein accumulation has been
      described in the Purkinje cells of MSA. We propose that MSA is another
      degenerative disorder associated with somatic sprouts of Purkinje cells.

PMID- 29575083
TI  - Survival of Cronobacter in powdered infant formula and their variation in biofilm
      formation.
AB  - : Cronobacter is a ubiquitous Gram-negative pathogen bacterium capable of
      surviving in low water activity environments, in particular powdered infant
      formula (PIF). Seven Cronobacter strains representing four different species (C.
      sakazakii, n = 4; C. malonaticus, n = 1; C. muytjensii, n = 1; C. turicensis, n =
      1) were subjected to dry stress and stored in PIF at room temperature. The
      resulting survivor curves showed that Cronobacter sp. can survive for extended
      periods of at least 3 months with a significant, but moderate, variability
      regarding the level of resistance between species; however, no correlation was
      evident regarding the origin of strains. These results are evaluated with regard
      to other key characteristics, including genomic profiles and biofilm formation
      capacities of the strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Cronobacter can
      survive extended periods of at least 3 months in PIF, with moderately significant
      interspecific variability in desiccation resistance. Results are evaluated with
      regard to genomic profiles and biofilm formation capacities of the strains, and
      contribute to an improved understanding of the environmental persistence of
      Cronobacter in contaminated PIF, and subsequent risk to infant exposure.

PMID- 29575084
TI  - Inhibition of PSMD4 alters ZP1 ubiquitination state and sperm-oocyte-binding
      ability in pigs.
AB  - The aim of this study was to determine how the duration of culture affects the
      ubiquitination of zona pellucida (ZP) proteins (ZP1, ZP2 and ZP3) during porcine
      oocyte maturation in vitro. We analysed the changes in ZP protein ubiquitination
      under three conditions: (i) during oocyte maturation from stage GV to MII; (ii)
      in oocytes cultured for different periods of time; and (iii) in oocytes treated
      with an antibody against PSMD4. Our results show that ZP1 and ZP2 are
      ubiquitinated at the GV stage, while ZP1, ZP2 and ZP3 are ubiquitinated at the
      MII stage, and band intensities for these proteins were significantly different
      between the GV and MII stages (p < .05). We also found that ubiquitination occurs
      in ZP1, ZP2 and ZP3 after cultured for 46, 52, 58 and 64 hr, and that the level
      of ubiquitinated ZP1 was significantly different in oocytes that were cultured
      for different time periods. Finally, treatment with an antibody against PSMD4
      resulted in a significant decrease in ZP1 ubiquitination (p < .05), without
      affecting ZP2 or ZP3. The number of attached sperms per oocyte was also
      significantly different between control and anti-PSMD4-treated groups. Thus, we
      concluded that ZP1 and ZP2 are ubiquitinated at the GV stage, and ZP1, ZP2 and
      ZP3 are ubiquitinated at the MII stage. As the duration of culture increases, the
      ubiquitination levels of ZP proteins decrease. We also found that PSMD4 improves
      ZP1 ubiquitination during in vitro culture of porcine oocytes and effectively
      inhibits sperm-oocyte binding.

PMID- 29575085
TI  - Associations of eHealth literacy with health-promoting behaviours among hospital
      nurses: A descriptive cross-sectional study.
AB  - AIMS: To investigate the associations of eHealth Literacy with health-promoting
      behaviours among hospital nurses in South Korea. BACKGROUND: Health-promoting
      behaviours of nurses are crucial for their own improved health and health-related
      behaviours of patients. eHealth literacy refers to the ability to search,
      understand and evaluate health information available online. With the growing use
      of the Internet, eHealth literacy is emerging as an important factor enhancing
      health-promoting behaviours. DESIGN: Descriptive cross-sectional design with self
      reported questionnaires. METHODS: Data were collected between March-May 2016 from
      five hospitals in South Korea. Health-promoting behaviours and eHealth literacy
      were assessed using Health Promoting Lifestyle Profile-II and K-eHEALS,
      respectively. Multiple linear regression models were used to examine the
      associations of eHealth literacy and health-promoting behaviours. RESULTS: Nurses
      with high level of eHealth literacy had significantly positive overall health
      promoting behaviours, stress management, interpersonal relations, self
      actualization and health responsibility, but not for nutrition and physical
      activity. CONCLUSION: Improving eHealth literacy through various strategies could
      be an effective way to boost health-promoting behaviours among nurses. However,
      improvement of actual health-promoting behaviours such as nutrition and physical
      activity will require systematic and organizational changes.

PMID- 29575086
TI  - Application of noninvasive prenatal testing in pregnancies with fetal double
      bubble sign: Is it feasible?
AB  - OBJECTIVE: To evaluate the application of noninvasive prenatal testing as an
      alternative to invasive diagnostic testing in pregnancies with the double bubble
      sign. METHODS: This was a retrospective analysis of 92 pregnancies with fetal
      double bubble identified by prenatal ultrasound, in which invasive diagnostic
      testing was performed for genetic investigations using quantitative fluorescence
      PCR and chromosomal microarray. Noninvasive prenatal testing was assumed to
      provide to patients for screening for the common aneuploidies. RESULTS: Fetal
      trisomy 21 was detected in 8 of the 92 patients with prenatal double bubble. No
      other chromosomal anomalies or microscopic pathogenic copy-number variations
      (CNV) were found. Noninvasive prenatal testing could theoretically identified the
      affected pregnancies with trisomy 21 in this group with decreased number of
      invasive diagnostic testing. CONCLUSIONS: Noninvasive prenatal testing could be
      recommended for genetic evaluation of the etiology of prenatal double bubble
      after thorough pretest counseling.

PMID- 29575087
TI  - Addressing sexual issues in palliative care: A qualitative study on nurses'
      attitudes, roles and experiences.
AB  - AIM: To explore palliative care nurses' attitudes, roles and concrete experience
      with regard to addressing sexual issues in their daily practice. BACKGROUND:
      Patients and their partners in palliative care might experience dramatic changes
      in their sexuality and want nurses to provide the opportunity to address them.
      Moreover, it is argued that the holistic philosophy of palliative care encourages
      nurses working in this area to include sexual issues in their daily care. It is,
      however, unknown how palliative care nurses address sexual issues. DESIGN: A
      generic qualitative study was performed. METHODS: In total, 21 in-depth
      interviews were done with nurses from different facilities of palliative care
      networks in Flanders. Data were collected between September 2014 - September 2016
      and thematic analysis was used to analyse the data. RESULTS: It was found that
      the way palliative care nurses addressed sexual issues was clearly influenced by
      their own interpretation of the philosophical principles underlying palliative
      care. The different interpretations of these basic principles create tensions for
      nurses about how to address sexual issues in the daily practice of palliative
      care and nurses vary in their reactions to these tensions. The present findings
      show that palliative care nurses - when they were able to overcome these tensions
      - use a "sex-positive approach" that fits with their tendency to focus on quality
      of life. CONCLUSION: Out of the results of this study, we made a list of good
      practices for palliative care nurses addressing sexual issues. This list can be
      used in nursing educational programs.

PMID- 29575088
TI  - Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone
      marrow molecular profile in myelodysplastic syndromes.

PMID- 29575089
TI  - Skin toxicology and 3Rs-Current challenges for public health protection.
AB  - Driven by the fast paced development of complex test systems in vitro, mass
      spectrometry and omics, we finally have the tools to unravel the molecular events
      that underlie toxicological adversity. Yet, timely regulatory adaptation of these
      new tools continues to pose major challenges even for organs readily accessible
      such as skin. The reasons for this encompass a need for conservatism as well as
      the need of tests to serve an existing regulatory framework rather than to
      produce scientific knowledge. It is important to be aware of this in order to
      align regulatory skin toxicity with the 3R principles more readily. While most
      chemical safety testing is still based on animal data, regulatory frameworks have
      seen a strong push towards non-animal approaches. The endpoints corrosion,
      irritation, sensitisation, absorption and phototoxicity, for example, can now be
      covered in vitro with the corresponding test guidelines (TGs) being made
      available by the OECD. However, in vitro approaches tend to be more reductionist.
      Hence, a combination of several tests is usually preferable to achieve satisfying
      predictivity. Moreover, the test systems and their combined use need to be
      standardised and are therefore subject not only to validation but also to the
      ongoing development of so-called integrated approaches to testing and assessment
      (IATAs). Concomitantly, skin models are being refined to deliver the complexity
      required for increased applicability and predictivity. Given the importance of
      regulatory applicability for 3R-derived approaches to have a long-lasting impact,
      this review examines the state of regulatory implementation and perspectives,
      respectively.

PMID- 29575090
TI  - Gait mechanics and tibiofemoral loading in men of the ACL-SPORTS randomized
      control trial.
AB  - The risk for post-traumatic osteoarthritis is elevated after anterior cruciate
      ligament reconstruction (ACLR), and may be especially high among individuals with
      aberrant walking mechanics, such as medial tibiofemoral joint underloading 6
      months postoperatively. Rehabilitation training programs have been proposed as
      one strategy to address aberrant gait mechanics. We developed the anterior
      cruciate ligament specialized post-operative return-to-sports (ACL-SPORTS)
      randomized control trial to test the effect of 10 post-operative training
      sessions consisting of strength, agility, plyometric, and secondary prevention
      exercises (SAPP) or SAPP plus perturbation (SAPP + PERT) training on gait
      mechanics after ACLR. A total of 40 male athletes (age 23 +/- 7 years) after
      primary ACLR were randomized to SAPP or SAPP + PERT training and tested at three
      distinct, post-operative time points: 1) after impairment resolution (Pre
      training); 2) following 10 training sessions (Post-training); and 3) 2 years
      after ACLR. Knee kinematic and kinetic variables as well as muscle and joint
      contact forces were calculated via inverse dynamics and a validated
      electromyography-informed musculoskeletal model. There were no significant
      improvements from Pre-training to Post-training in either intervention group.
      Smaller peak knee flexion angles, extension moments, extensor muscle forces,
      medial compartment contact forces, and tibiofemoral contact forces were present
      across group and time, however the magnitude of interlimb differences were
      generally smaller and likely not meaningful 2 years postoperatively. Neither SAPP
      nor SAPP + PERT training appears effective at altering gait mechanics in men in
      the short-term; however, meaningful gait asymmetries mostly resolved between post
      training and 2 years after ACLR regardless of intervention group. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:2364-2372, 2018.

PMID- 29575091
TI  - Transgender adolescents and acne: A cases series.
AB  - We describe the difficulties of treating acne in a series of female-to-male
      transgender adolescents, including concerns about potential hepatotoxicity with
      concomitant use of testosterone with isotretinoin or tetracyclines. Acne is a
      foreseeable adverse effect of testosterone treatment in transgender adolescents,
      so monitoring for acne is advised. The treatment of acne in transgender
      adolescents is important given that severe acne and transgenderism are associated
      with higher rates of depression and suicide.

PMID- 29575092
TI  - Novel biomarker, phosphorylated T-LAK cell-originated protein kinase (p-TOPK) can
      predict outcome in primary central nervous system lymphoma.
AB  - This study aimed to assess whether T-lymphokine-activated killer cell-originated
      protein kinase (TOPK) can be a potent novel biomarker to predict the outcome in
      patients with primary central nervous system lymphoma (PCNSL). This study
      enrolled 20 patients who were histologically diagnosed as having diffuse large B
      cell type PCNSL between 2005 and 2015. Using surgical specimens, the expression
      of TOPK and phosphorylated TOPK (p-TOPK) was analyzed on immunohistochemistry.
      Clinical features such as age, sex, Karnofsky performance status (KPS), ocular
      involvement, deep brain structure involvement, the number of lesions,
      chemotherapy and radiation therapy were also collected. Impacts of TOPK/p-TOPK
      expression on their progression-free survival (PFS) and overall survival (OS)
      were examined with multivariate analysis. Median PFS/OS were 24.2 and 39.0
      months, respectively. On immunostaining, the mean percentage of TOPK-positive
      cells was 35.5 +/- 20.8%, and the mean number of p-TOPK-positive cells was 13.7
      +/- 15.7 cells/mm2 . The higher expression of p-TOPK was significantly related to
      multiple lesions (P = 0.003). Multivariate analysis demonstrated that only the
      higher expression of p-TOPK was an independent predictor to shorten both PFS (P =
      0.029; hazard ratio (HR), 5.5; 95% confidential interval (CI), 1.2-25.3) and OS
      (P = 0.014; HR, 7.7; 95% CI, 1.5-41.3). These findings strongly suggest that p
      TOPK may be a potent biomarker to determine the outcome of patients with PCNSL
      and to develop novel drugs to treat PCNSL.

PMID- 29575093
TI  - Arabidopsis thaliana Raf22 protein kinase maintains growth capacity during
      postgerminative growth arrest under stress.
AB  - When seeds are exposed to drought and salinity during germination, newly
      germinated embryos stop growth and enter a quiescent state called postgerminative
      growth (PGG) arrest. PGG arrest protects embryos from the stress, but it is not
      known how PGG is restored from the arrest when stress is eased. In this study, we
      show that under stress- or abscisic acid-induced PGG arrest conditions,
      Arabidopsis thaliana Raf-type protein kinase 22 (AtRaf22) overexpression
      accelerated photoautotrophic seedling establishment, whereas atraf22 knockout
      mutations enhanced the arrest. Furthermore, when the stress intensity was reduced
      subsequently, AtRaf22 overexpression plants resumed growth and accomplished
      photoautotrophic transition much faster than the knockout or wild-type plants.
      These results suggest that AtRaf22 activity is important for maintaining growth
      capacity during stress-induced PGG arrest, which is most likely critical for
      competitive growth when the stress subsides and plants resume growth. Such a
      factor has not been reported before.

PMID- 29575095
TI  - Spinal muscular atrophy with respiratory distress type 1 associated with novel
      compound heterozygous mutations in IGHMBP2: Differential diagnosis in a case with
      congenital diaphragm eventration.

PMID- 29575096
TI  - Clinical application of endothelial injury marker in hypertensive patients.
AB  - PURPOSE: Endothelial damages are one of the most important causes of persistent
      hypertensive complications. The aim of our study was to discuss the relationship
      between the molecular markers of endothelial damage, thrombomodulin, and
      complications in hypertension. METHODS: A total 132 cases of hypertensive
      patients, including 13 patients with damage of target organs, were selected as
      research subjects. And grouping was based on different levels of blood pressure.
      The blood pressure and thrombomodulin levels were detected among all cases, and
      their drinking, smoking, and other medical records were tracked. RESULTS: Higher
      plasma concentration of thrombomodulin was demonstrated in subjects with
      hypertensive complications compared with without complications [24.5 (18.1,37.55)
      vs 12.1 (9.1,22.3) TU/mL, P = .001, respectively]. The optimum thrombomodulin
      cutoff value was determined to be more than 15.5 TU/mL, with a sensitivity of
      92.3% and a specificity of 63%. With the increase in blood pressure level,
      thrombomodulin levels in three groups gradually raised [6.15(5.475,12.75) vs
      9.75(7.725,13.35) vs 16.45 (10.125,23.725) TU/mL, P = .007, respectively].
      CONCLUSION: With the increase in blood pressure and the occurrence of
      complications, thrombomodulin showed an increasing trend, which was caused by an
      increase in the degree of endothelial injury. So, thrombomodulin may serve as a
      clinically meaningful marker of the progression of hypertension.

PMID- 29575097
TI  - Evaluation and Comparison of Hemodynamic Performance of Three ECLS Systems in a
      Simulated Adult Cardiogenic Shock Model.
AB  - The objective of this study was to evaluate three commercially available ECLS
      systems with rotary pumps in terms of circuit pressure, pressure drop, perfusion
      modes, and hemodynamic energy transmission in a simulated adult cardiogenic shock
      model. One circuit consisted of a Cardiohelp system, which included a Cardiohelp
      console and HLS Module Advanced 7.0 tubing set with integrated centrifugal pump
      and oxygenator. The alternative circuit was composed of a Quadrox-D Adult
      oxygenator connected in series with either an i-cor diagonal pump and console or
      a Rotaflow centrifugal pump and console. The circuit was primed with lactated
      Ringer's solution and packed red blood cells (hematocrit 40%). The trials were
      conducted at flow rates of 1-5 L/min with pseudo patient pressures of 60 mm Hg
      and 80 mm Hg. Pulsatile flow was tested when using the i-cor system. Mean pre
      oxygenator pressure and pressure drop across ECLS circuit (including oxygenator
      and arterial tubing) were lower when using the Cardiohelp system as compared to
      the Rotaflow and i-cor systems (P < 0.01). The i-cor system was able to deliver
      more hemodynamic energy to the pseudo patient because of its ability to produce
      pulsatile flow (P < 0.01). The Cardiohelp HLS Module Advanced 7.0 integrated
      oxygenator had a lower resistance than the Quadrox-D oxygenator. Although the
      compact Cardiohelp system had a better hemodynamic performance when compared to
      Rotaflow and i-cor systems, the pulsatile flow of the i-cor system delivered more
      hemodynamic energy to the pseudo patient. This may render more physiological
      benefits in high-risk patients on ECLS.

PMID- 29575094
TI  - The relationship between frailty and polypharmacy in older people: A systematic
      review.
AB  - AIMS: Frailty is a complex geriatric syndrome resulting in decreased
      physiological reserves. Frailty and polypharmacy are common in older adults and
      the focus of extensive studies, although little is known about the impact they
      may have on each other. This is the first systematic review analysing the
      available evidence on the relationship between frailty and polypharmacy in older
      adults. METHODS: Systematic review of quantitative studies. A comprehensive
      literature search for publications in English or Spanish was performed on
      MEDLINE, CINAHL, the Cochrane Database and PsycINFO in September 2017 without
      applying restrictions on the date of publication. Studies reporting any
      relationship between frailty and polypharmacy in older adults were considered.
      RESULTS: A total of 25 publications were included, all of them observational
      studies. Evaluation of Fried's frailty criteria was the most common approach,
      followed by the Edmonton Frail Scale and FRAIL scale. Sixteen of 18 cross
      sectional analyses and five of seven longitudinal analyses demonstrated a
      significant association between an increased number of medications and frailty.
      The causal relationship is unclear and appears to be bidirectional. Our analysis
      of published data suggests that polypharmacy could be a major contributor to the
      development of frailty. CONCLUSIONS: A reduction of polypharmacy could be a
      cautious strategy to prevent and manage frailty. Further research is needed to
      confirm the possible benefits of reducing polypharmacy in the development,
      reversion or delay of frailty.

PMID- 29575098
TI  - Virtual learning communities for faculty members: does WhatsApp work?

PMID- 29575099
TI  - Lack of association between SLCO1B1 polymorphisms and lipid-lowering response to
      simvastatin therapy in Thai hypercholesterolaemic patients.
AB  - WHAT IS KNOWN: SLCO1B1 polymorphisms have been reported to affect the responses
      to statin therapy. However, the association of these polymorphisms and lipid
      lowering responses has been inconsistent. OBJECTIVE: To investigate the effect of
      SLCO1B1 c.388A>G, c.521T>C and g.89595T>C polymorphisms on the lipid-lowering
      response to simvastatin therapy in Thai hypercholesterolaemic patients. METHODS:
      Three hundred and 91 hypercholesterolaemic patients in Southern Thailand were
      enrolled and treated with simvastatin 20 or 40 mg per day. Among them, 191 and
      200 patients were treated for 3 and 12 months, respectively. Serum lipids were
      measured before and after the treatment. SLCO1B1 c.388A>G, c.521T>C and
      g.89595T>C polymorphisms were analysed using polymerase chain reaction-high
      resolution melting (PCR-HRM). RESULTS: The allele frequencies of the SLCO1B1
      c.388A>G, c.521T>C and g.89595T>C polymorphisms in Thai hypercholesterolaemic
      patients were 74.9%, 11.8% and 37.2%, respectively. After treatment with 20-40 mg
      simvastatin daily for 3 and 12 months, TC, TG and LDL-C concentrations were
      significantly lower than at baseline (P < .05). However, there was no a
      significant change in serum HDL-C after simvastatin treatment for 3 and 12 months
      (P > .05). Moreover, there was no association between SLCO1B1 c.388A>G, c.521T>C
      and g.89595T>C polymorphisms and lipid-lowering response to 3 and 12 months of
      either 20 or 40 mg/day simvastatin treatment. WHAT IS NEW AND CONCLUSION: SLCO1B1
      c.388A>G, c.521T>C and g.89595T>C polymorphisms may not be useful as genetic
      markers of lipid-lowering response to simvastatin therapy in Thai
      hypercholesterolaemic patients.

PMID- 29575100
TI  - Hemoglobin response to ferric citrate in patients with nondialysis-dependent
      chronic kidney disease and iron deficiency anemia.

PMID- 29575101
TI  - Adherent agarose mold cultures: An in vitro platform for multi-factorial
      assessment of passaged chondrocyte redifferentiation.
AB  - Generating the best possible bioengineered cartilage from passaged chondrocytes
      requires culture condition optimization. In this study, the use of adherent
      agarose mold (adAM) cultures to support redifferentiation of passaged twice (P2)
      chondrocytes and serve as a scalable platform to assess the effect of growth
      factor combinations on proteoglycan accumulation by cells was examined. By 2 days
      in adAM culture, bovine P2 cells were partially redifferentiated as demonstrated
      by regression of actin-based dedifferentiation signalling and fibroblast matrix
      and contractile gene expression. By day 10, aggrecan and type II collagen gene
      expression were significantly increased in adAM cultured cells. At day 20, a
      continuous layer of cartilage tissue was observed. There was no evidence of
      tissue contraction by P2 cells in adAM cultures. The matrix properties of the
      resultant tissue as well as proteoglycan 4 (PRG4) secreted by the cells were
      dependent on the initial cell seeding density. AdAM cultures were scalable and
      culture within small 3 mm diameter adAM allowed for multi-factorial assessment of
      growth factors on proteoglycan accumulation by human P2 chondrocytes. Although
      there was a patient specific response in proteoglycan accumulation to the various
      cocktail combinations, the cocktail consisting of 2 ng/ml TGFbeta1, 10 ng/ml
      FGF2, and 250 ng/ml FGF18 resulted in a consistent increase in alcian blue tissue
      staining. Additional studies will be required to identify the optimal conditions
      to bioengineer articular cartilage tissue for clinical use. However, the results
      to date suggest that adAM cultures may be suitable to use for high throughput
      assessment. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 36:2392-2405, 2018.

PMID- 29575102
TI  - Necessary changes to improve animal models.
AB  - Animal models evolved from sire models and inherited some issues that affected
      sire models. Those issues include definition and treatment of contemporary
      groups, accounting for time trends and dealing with animals having unknown
      parents. The assumptions and limitations of the animal model need to be kept in
      mind. This review of the animal model will discuss the issues and will recommend
      enhancements to animal models for future applications.

PMID- 29575103
TI  - Contributions to quantitative genetic models by Yule and by Weinberg prior to
      Fisher 1918.

PMID- 29575104
TI  - Genomic selection-the final step or another step in an endless race?

PMID- 29575105
TI  - Method for the estimation of genetic merit of animals with uncertain paternity
      under Bayesian inference.
AB  - The use of controlled mating or artificial insemination is impracticable in the
      case of large herds, mainly because of labour costs and the need to delimit areas
      during the breeding period. However, the exclusion of information from animals
      with uncertain paternity reduces genetic progress. The objectives of this study
      were as follows: (i) propose an iterative empirical Bayesian procedure to
      implement the hierarchical animal model (ITER); (ii) calculate the posterior
      probabilities of paternity by the maximum likelihood method following the
      concepts; (iii) compare an average numerator relationship matrix (ANRM), Bayesian
      hierarchical (HIER) models and ITER. Records of Nellore animals born between 1984
      and 2006 from the zootechnical archive of Agropecuaria Jacarezinho Ltda were
      used. For data consistency, records of contemporary groups (CGs) with fewer than
      three animals and animals whose records were 3.5 standard deviations above or
      below the mean of their CG were eliminated. After editing the data, 62,212
      animals in the file and 12,876 animals in pedigree file were maintained,
      respectively. Spearman and Pearson correlations between the posterior mean of the
      genetic effects of animals were calculated to compare the ranking of animals for
      selection. Simulated data were used to confirm the veracity of the model. The
      correlations between ITER and HIER and between ITER and ANRM were similar
      evaluating different files, which decreased at the same proportion when only high
      ranked animals were evaluated. In conclusion, the model proposed herein is a
      suitable computational alternative to improve the prediction of breeding values
      of animals in genetic evaluations using large databases, including animals with
      uncertain paternity.

PMID- 29575106
TI  - Antifungal treatment in haematological and oncological patients: Need for quality
      assessment in routine care.
AB  - Invasive fungal infections in haematological and oncological patients have a
      major impact on morbidity, mortality and treatment costs. Therefore, rational use
      of antifungal agents is important for optimal patient care and resource use. The
      study's objective was to analyse antifungal usage in a German tertiary teaching
      hospital, department of haematology and oncology, to evaluate quality of
      antifungal treatment and to assess the need for an antifungal stewardship
      programme. This retrospective observational study included patients >=18 years
      receiving systemic antifungals for prophylaxis or therapy of invasive fungal
      infection between January and June 2016. Appropriateness of antifungal
      prescriptions was evaluated in accordance with guidelines of the German Society
      of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%)
      patients received antifungals. One hundred seventy-one antifungals were
      prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In
      127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice
      of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty
      four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to
      moderate, 29 severe interactions). Results of this analysis demonstrate that use
      of systemic antifungals in routine care differs in a substantial number of
      patients from guideline and labelling recommendations. To optimise antifungal
      use, the implementation of antifungal stewardship programmes seems to be
      justified.

PMID- 29575107
TI  - Nonfullerene Tandem Organic Solar Cells with High Performance of 14.11.
AB  - Fabricating solar cells with tandem structure is an efficient way to broaden the
      photon response range without further increasing the thermalization loss in the
      system. In this work, a tandem organic solar cell (TOSC) based on highly
      efficient nonfullerene acceptors (NFAs) with series connection type is
      demonstrated. To meet the different demands of front and rear sub-cells, two NFAs
      named F-M and NOBDT with a whole absorption range from 300 to 900 nm are
      designed, when blended with 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) and narrow bandgap polymer PTB7-Th, respectively, the PBDB-T: F-M system
      exhibits a high Voc of 0.98 V and the PTB7-Th: NOBDT system shows a remarkable
      Jsc of 19.16 mA cm-2 , which demonstrate their potential in the TOSCs. With the
      guidance of optical simulation, by systematically optimizing the thickness of
      each layer in the TOSC, an outstanding power conversion efficiency of 14.11%,
      with a Voc of 1.71 V, a Jsc of 11.72 mA cm-2 , and a satisfactory fill factor of
      0.70 is achieved; this result is one of the top efficiencies reported to date in
      the field of organic solar cells.

PMID- 29575108
TI  - Coumarin/BODIPY Hybridisation for Ratiometric Sensing of Intracellular Polarity
      Oscillation.
AB  - With different polarity responses, coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (BODIPY) were hybridised to construct polarity fluorescent sensors, CBDP
      and iso-CBDP, to overcome the disadvantages of solvatochromic sensors in
      ratiometric polarity sensing. Only CBDP displayed an emission ratio (ICou /IBDP ,
      coumarin to BODIPY emissions) that increased with an exponential dependence on
      medium relative permittivity over a wide polarity range (epsilonr <57.9). This
      sensing ability of CBDP was not affected by medium pH; viscosity; and most
      intracellular species, especially reactive oxygen, nitrogen, and sulfur species.
      Apart from local cytoplasmic polarity quantification through lambda imaging, CBDP
      enables real-time ratiometric imaging for intracellular polarity oscillation
      induced by oxidative stimulation. Ratiometric polarity flow cytometry was
      developed, for the first time, with CBDP, which demonstrated that a high
      concentration H2 O2 induced cytoplasmic polarity enhancement, whereas pre
      incubation with N-acetyl-l-cysteine inhibited this effect.

PMID- 29575109
TI  - Patterns of carer distress over time in mild dementia.
AB  - OBJECTIVE: To study the level of carer reported distress in mild dementia, over a
      3-year period. METHODS: This study is part of the Norwegian DemVest-study and
      utilises data from carers of people with mild dementia (n = 223). Those diagnosed
      with dementia with Lewy bodies (DLB, n = 63) and Alzheimer's disease (AD, n = 97)
      were included together with other dementia types (n = 63). The Relatives' Stress
      Scale was used to assess the level of reported distress in carers. Descriptive
      and a linear mixed effects models including diagnosis, time, and the interaction
      between time and diagnosis were performed. RESULTS: Carer distress in mild
      dementia increased significantly over time (P = 0.011), particularly from
      baseline until 2 (P = 0.001) years follow-up. Carer distress in people caring for
      those with AD increased significantly, from baseline until 2 (P = 0.047) and 3 (P
      = 0.019) years follow-up. Distress in carers of people with DLB was high at
      baseline and remained relatively stable across the 3-year period. However,
      admission to a nursing home during the first year of follow-up was associated
      with a significantly lower reported carer distress in those caring for a person
      with DLB (P = 0.002), compared with those caring for a person with DLB living at
      home. CONCLUSION: Being a carer to a person with mild dementia is associated with
      increasing distress. However, the burden of distress changes with the diagnosis,
      time, and situation, which highlights the dynamic nature of the caring role.
      Findings have important implications for health services for people diagnosed
      with mild dementia and their carers.

PMID- 29575110
TI  - Percutaneous coronary intervention: 2017 in review.
AB  - In an effort to keep the interventional community up-to-date with the abundant
      amount of new data, we have selected what we believe to be the most important
      publications in percutaneous coronary intervention from January 1, 2017 to
      December 2017.

PMID- 29575111
TI  - Epilobium spp: Pharmacology and Phytochemistry.
AB  - The Epilobium species and their extracts are very popular in folk medicine, for a
      wide range of applications. The purpose of this review is the analysis of the
      pharmacological properties of Epilobium spp, considering whether their effects
      (e.g., anti-inflammatory, antioxidant, antitumor, antimicrobial, analgesic, and
      antiandrogenic) could rationally justify the use of Epilobium as a treatment of
      numerous diseases. Even if numerous preclinical studies have been reported,
      randomized controlled clinical trials (for the evaluation of safety and
      efficacy), and eventually cost-effectiveness studies (to estimate the long-term
      cumulative costs), are still needed to confirm the usefulness of these medicinal
      plants in human diseases.

PMID- 29575112
TI  - The what, when, and why of human prostate cancer xenografts.
AB  - BACKGROUND: Presently, ~85 serially transplantable human prostate cancer
      xenografts spanning the phenotypic, epigenetic, and genetic heterogeneity seen
      clinically are available in a variety of laboratories throughout the world. If
      distributed to the prostate cancer research community, these can provide an
      experimental platform for resolving the specificity versus generalizability of
      basic cancer biology principles (eg, credentialing of therapeutic molecular
      targets) and for validating translational approaches for prevention, diagnosis,
      and therapy. Thus, there is an urgent need to distribute the already established
      serially transplantable human prostate cancer xenografts and to develop robust
      methods for establishing new ones. METHODS: To accelerate the development of such
      additional xenografts, particularly from patients treated with the newer standard
      of care agents (ie, abiraterone, enzalutamide, cabazitaxel, alpharadin, etc), a
      historic review of the field will be presented. RESULTS: Over the last 50 years,
      multiple groups throughout the world have developed methods for the successful
      establishment of serially transplantable human prostate cancer xenografts using a
      variety of immune deficient mice. These are summarized chronologically.
      CONCLUSIONS AND FUTURE: With the ever growing appreciation of the value of
      personalized medicine (aka precision medicine), methods need to be developed that
      allow efficient and timely growth of primary patient derived prostate cancer
      xenografts (PDXs), which can be used as "avatars" for defining optimal therapy
      for that specific patient. Such development should be based upon the leads
      obtained from the successful establishment of serially transplantable prostate
      cancer xenografts described in this review.

PMID- 29575113
TI  - Renal volume assessed by magnetic resonance imaging volumetry correlates with
      renal function in living kidney donors pre- and postdonation: a retrospective
      cohort study.
AB  - Renal function of potential living kidney donors is routinely assessed with
      scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic
      resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good
      predictor of kidney function pre- and postdonation. We retrospectively analyzed
      the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated
      with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine
      clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by
      Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD)
      formula pre- and postdonation during a follow-up of 3 years. RV correlated
      significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between
      RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in
      comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly
      correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after
      donation. MRI renal volumetry might be an alternative technique for the
      evaluation of split renal function and prediction of renal function postdonation
      in living kidney donors.

PMID- 29575114
TI  - American council on ECP (ACE): Why now?
AB  - Stimulated by the scientific progress in deciphering the principal elements
      contributing to the clinical efficacy of extracorporeal photochemotherapy (ECP),
      the American Council on ECP (ACE) was formed, under the auspices of the American
      Society for Apheresis (ASFA), to develop a field-guiding Consensus Report. ACE is
      composed of thirty nationally recognized ECP experts, clinically spanning cancer,
      transplantation, and autoimmunity and scientifically bridging immunology,
      bioengineering, and hematology. The two-day meeting took place in Manhattan,
      April 13-14, 2017, and unanimous consensus on nine pivotal points is herein
      reported. (1) ECP's clinical evolution must now enter a scientifically driven
      phase. (2) ECP is currently a bidirectional therapy, both immunizing and
      tolerizing simultaneously, via a single one-size-fits-all inflexible medical
      device. (3) To preclude inadvertent tolerization in the cancer setting, or
      immunization in the transplant rejection setting, polarization of ECP to either
      immunization or tolerization mode to match the clinical need is now possible and
      necessary. (4) Cutaneous T cell lymphoma (CTCL) is a genetically driven cancer,
      whose response to ECP is due to enhanced anti-cancer immunity. (5) ECP is a
      dendritic antigen-presenting cell (DC) based therapy. (6) ECP's efficacy can now
      be tested in a broad array of cancers. (7) ECP's capacity to tolerize to
      allotransplants via processing of donor leukocytes merits expedited human
      investigation. (8) UVA-8-MOP-impacted ECP-induced DC are potent antigen-specific
      tolerizing agents, while UVA-8-MOP(8-Methoxypsoralen)-spared ECP-induced DC are
      potent antigen-specific immunizing agents. (9) Six pilot clinical trial areas
      (CTCL, graft-vs.-host disease, ovarian carcinoma, anti-graft cytotoxic
      antibodies, pemphigus vulgaris, and haplotype mismatched stem cell transplants)
      are advised. ACE will be an ongoing advisory group for the field, with the goal
      of overseeing coordinated clinical and fundamental research efforts.

PMID- 29575115
TI  - Lipid profile and incidence of atrial fibrillation: A prospective cohort study in
      China.
AB  - BACKGROUND: The association between dyslipidemia, a major risk factor for
      cardiovascular diseases, and atrial fibrillation (AF) is not clear because of
      limited evidence. HYPOTHESIS: Dyslipidemia may be associated with increased risk
      of AF in a Chinese population. METHODS: A total of 88 785 participants free from
      AF at baseline (2006-2007) were identified from the Kailuan Study. Fasting levels
      of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured at
      baseline using standard procedures. The study population was stratified based on
      quartiles of lipid profile. Incident AF was ascertained from electrocardiograms
      at biennial follow-up visits (2008-2015). The associations between incident AF
      and the different lipid parameters (TC, LDL-C, HDL-C, and TG) were assessed by
      Cox proportional hazards regression analysis. RESULTS: Over a mean follow-up
      period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]:
      0.60, 95% confidence interval [CI]: 0.43-0.84) and LDL-C (HR: 0.60, 95% CI: 0.43
      0.83) levels were inversely associated with incident AF after multivariable
      adjustment. HDL-C and TG levels showed no association with newly developed AF.
      The results remained consistent after exclusion of individuals with myocardial
      infarction or cerebral infarction, or those on lipid-lowering therapy. Both
      TC/HDL-C and LDL-C/HDL-C ratios were inversely associated with risk of AF (per
      unit increment, HR: 0.88, 95% CI: 0.79-0.98 and HR: 0.77, 95% CI: 0.66-0.91,
      respectively). CONCLUSIONS: TC and LDL-C levels were inversely associated with
      incident AF, whereas no significant association of AF with HDL-C or TG levels was
      observed.

PMID- 29575116
TI  - Making the best use of data not created for research.

PMID- 29575117
TI  - Postnatal maturation of microglia is associated with alternative activation and
      activated TGFbeta signaling.
AB  - Microglia are involved in a widespread set of physiological and pathological
      processes and further play important roles during neurodevelopmental events.
      Postnatal maturation of microglia has been associated with the establishment of
      microglia-specific gene expression patterns. The mechanisms governing microglia
      maturation are only partially understood but Tgfbeta1 has been suggested to be
      one important mediator. In the present study, we demonstrate that early postnatal
      microglia maturation is associated with alternative microglia activation,
      increased engulfment of apoptotic cells as well as activated microglial Tgfbeta
      signaling. Interestingly, microglial Tgfbeta signaling preceded the induction of
      the microglia-specific gene expression indicating the importance of Tgfbeta1 for
      postnatal microglia maturation. Moreover, we provide evidence that Tgfbeta1 is
      expressed by neurons in postnatal and adult brains defining neuron-microglia
      communication via Tgfbeta1 as an important event. Finally, we introduce the
      recently identified microglia marker Tmem119 as a direct Tgfbeta1-Smad2 target
      gene. Taken together, the data presented here further increase the understanding
      of Tgfbeta1-mediated effects in microglia and place emphasis on the importance of
      Tgfbeta1 for microglia maturation and maintenance.

PMID- 29575118
TI  - Novel PSTPIP1 gene mutation in pyoderma gangrenosum, acne and suppurative
      hidradenitis syndrome.

PMID- 29575119
TI  - In Situ Activation of 3D Porous Bi/Carbon Architectures: Toward High-Energy and
      Stable Nickel-Bismuth Batteries.
AB  - To achieve high-energy and stable aqueous rechargeable batteries, state-of-the
      art of anode materials are needed. Bismuth (Bi) has recently emerged as an
      attractive anode material due to its highly reversible redox reaction and
      suitable negative operating working window. However, the capacity and durability
      of currently reported Bi anodes are still far from satisfactory. Here, an in situ
      activation strategy is reported to prepare a 3D porous high-density Bi
      nanoparticles/carbon architecture (P-Bi-C) as an efficient anode for nickel
      bismuth batteries. Taking advantages of the fast channels for charge transfer and
      ion diffusion, enhanced wettability, and accessible surface area, the highly
      loaded P-Bi-C electrode delivers a remarkable capacity of 2.11 mA h cm-2 as well
      as high rate capability (1.19 mA h cm-2 at 120 mA cm-2 ). To highlight, a robust
      aqueous rechargeable Ni//Bi battery based on the P-Bi-C anode is first
      constructed, achieving decent capacity (141 mA h g-1 ), impressive durability
      (94% capacity retention after 5000 cycles), and admirable energy density (16.9 mW
      h cm-3 ). This work paves the way for designing superfast nickel-bismuth
      batteries with high energy and long-life and may inspire new development for
      aqueous rechargeable batteries.

PMID- 29575120
TI  - Determination of Normal Skin Elasticity by Using Real-time Shear Wave
      Elastography.
AB  - OBJECTIVES: To define the reference ranges of normal skin elasticity measurements
      associated with shear wave elastography (SWE) in healthy volunteers and analyze
      the factors that may affect SWE. METHODS: Mean skin thickness and elastic modulus
      values from 90 healthy volunteers were evaluated with B-mode ultrasonography and
      SWE in the right fingers and forearms, anterior chest, and abdominal walls.
      Reference ranges of normal skin elasticity were calculated by using lower and
      upper limits at the 2.5th and 97.5th percentiles. To investigate the effects of
      potential factors (site, sex, age, body mass index, and skin thickness) on skin
      elasticity measurements, a 1-way analysis of variance, the Student t test, and
      the Pearson correlation test were performed. RESULTS: Skin elasticity was
      significantly different at different sites (P < .05). Mean elastic modulus values
      were 30.3 kPa for the finger, 14.8 kPa for the forearm, 17.8 kPa for the chest
      wall, and 9.5 kPa for the abdominal wall, and reference ranges of normal skin
      elasticity were 12.1 to 48.4kPa for the finger, 3.5 to 26.0 kPa for the forearm,
      6.6 to 28.9 kPa for the chest wall, and 3.5 to 15.5 kPa for the abdominal wall.
      Our study revealed that men had higher skin elasticity measurements than women (P
      < .05), and they were more elevated in participants aged 20 to 50 years than in
      the other groups at the finger (P < .05). The body mass index and skin thickness
      had a negligible impact on skin elasticity measurements (P > .05). CONCLUSIONS:
      This study revealed that the site, sex, and age should be taken into account when
      determining the reference ranges of normal skin elasticity by skin elasticity
      measurements.

PMID- 29575121
TI  - Manuka honey and methylglyoxal increase the sensitivity of Staphylococcus aureus
      to linezolid.
AB  - : The continued emergence and global spread of bacterial antibiotic resistance
      has fuelled the search for novel antimicrobial agents and resistance-modifying
      compounds. Manuka honey has both antimicrobial properties and the ability to
      increase the efficacy of FDA-approved antibiotic drugs. Compared to other types
      of honey, manuka honey contains elevated levels of methylglyoxal (MGO), a small
      molecule that contributes to its antibacterial activity. Manuka honey has shown
      particular promise for the treatment of antibiotic-resistant Gram-positive
      organisms such as methicillin-resistant Staphylococcus aureus. Linezolid is an
      oxazolidinone antibiotic used in the treatment of infections caused by a range of
      Gram-positive pathogens. Here, we demonstrate that manuka honey, as well as MGO
      in isolation, increases the sensitivity of S. aureus to linezolid in both agar
      diffusion and broth microdilution assays. This synergistic interaction is
      mediated in part by increased intracellular accumulation of linezolid in the
      presence of MGO. SIGNIFICANCE AND IMPACT OF THE STUDY: Manuka honey is widely
      recognized for its antimicrobial activity. Our study adds to the growing body of
      evidence that manuka honey and its active ingredient, methylglyoxal (MGO), can
      also function as antibiotic adjuvants. In this study, we provide the first report
      of synergy between MGO and linezolid against Staphylococcus aureus. Both manuka
      honey and purified MGO significantly increased the sensitivity of S. aureus to
      linezolid.

PMID- 29575123
TI  - First Japanese case of atypical Spitz tumor exhibiting ROS1 rearrangement.

PMID- 29575124
TI  - Asymmetric Synthesis of Diarylmethyl Sulfones by Palladium-Catalyzed
      Enantioselective Benzylic Substitution: A Remarkable Effect of Water.
AB  - A Pd/(R)-BINAP-catalyzed enantioselective benzylic sulfonation of diarylmethyl
      carbonates with sodium sulfinates proceeds to deliver the corresponding chiral
      diarylmethyl sulfones in good yields with high enantioselectivity. The reaction
      occurs in a dynamic kinetic asymmetric transformation (DYKAT) manner and thus
      provides convergent access to optically active benzylic sulfones from racemic
      secondary benzylic carbonates. Additionally, the addition of H2 O is found to be
      critical for high enantioselectivity.

PMID- 29575122
TI  - Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through
      SIRT1-PGC1alpha pathway.
AB  - Myocardial contractile dysfunction is associated with an increase in
      mitochondrial fission in patients with diabetes. However, whether mitochondrial
      fission directly promotes diabetes-induced cardiac dysfunction is still unknown.
      Melatonin exerts a substantial influence on the regulation of mitochondrial
      fission/fusion. This study investigated whether melatonin protects against
      diabetes-induced cardiac dysfunction via regulation of mitochondrial
      fission/fusion and explored its underlying mechanisms. Here, we show that
      melatonin prevented diabetes-induced cardiac dysfunction by inhibiting dynamin
      related protein 1 (Drp1)-mediated mitochondrial fission. Melatonin treatment
      decreased Drp1 expression, inhibited mitochondrial fragmentation, suppressed
      oxidative stress, reduced cardiomyocyte apoptosis, improved mitochondrial
      function and cardiac function in streptozotocin (STZ)-induced diabetic mice, but
      not in SIRT1-/- diabetic mice. In high glucose-exposed H9c2 cells, melatonin
      treatment increased the expression of SIRT1 and PGC-1alpha and inhibited Drp1
      mediated mitochondrial fission and mitochondria-derived superoxide production. In
      contrast, SIRT1 or PGC-1alpha siRNA knockdown blunted the inhibitory effects of
      melatonin on Drp1 expression and mitochondrial fission. These data indicated that
      melatonin exerted its cardioprotective effects by reducing Drp1-mediated
      mitochondrial fission in a SIRT1/PGC-1alpha-dependent manner. Moreover, chromatin
      immunoprecipitation analysis revealed that PGC-1alpha directly regulated the
      expression of Drp1 by binding to its promoter. Inhibition of mitochondrial
      fission with Drp1 inhibitor mdivi-1 suppressed oxidative stress, alleviated
      mitochondrial dysfunction and cardiac dysfunction in diabetic mice. These
      findings show that melatonin attenuates the development of diabetes-induced
      cardiac dysfunction by preventing mitochondrial fission through SIRT1-PGC1alpha
      pathway, which negatively regulates the expression of Drp1 directly. Inhibition
      of mitochondrial fission may be a potential target for delaying cardiac
      complications in patients with diabetes.

PMID- 29575125
TI  - A unified hierarchical oscillatory network model of head direction cells,
      spatially periodic cells, and place cells.
AB  - Spatial cells in the hippocampal complex play a pivotal role in the navigation of
      an animal. Exact neural principles behind these spatial cell responses have not
      been completely unraveled yet. Here we present two models for spatial cells,
      namely the Velocity Driven Oscillatory Network (VDON) and Locomotor Driven
      Oscillatory Network. Both models have basically three stages in common such as
      direction encoding stage, path integration (PI) stage, and a stage of
      unsupervised learning of PI values. In the first model, the following three
      stages are implemented: head direction layer, frequency modulation by a layer of
      oscillatory neurons, and an unsupervised stage that extracts the principal
      components from the oscillator outputs. In the second model, a refined version of
      the first model, the stages are extraction of velocity representation from the
      locomotor input, frequency modulation by a layer of oscillators, and two cascaded
      unsupervised stages consisting of the lateral anti-hebbian network. The principal
      component stage of VDON exhibits grid cell-like spatially periodic responses
      including hexagonal firing fields. Locomotor Driven Oscillatory Network shows the
      emergence of spatially periodic grid cells and periodically active border-like
      cells in its lower layer; place cell responses are found in its higher layer.
      This model shows the inheritance of phase precession from grid cell to place cell
      in both one- and two-dimensional spaces. It also shows a novel result on the
      influence of locomotion rhythms on the grid cell activity. The study thus
      presents a comprehensive, unifying hierarchical model for hippocampal spatial
      cells.

PMID- 29575126
TI  - Complete response of extramammary Paget's disease with imiquimod and PDT: Report
      of two cases.

PMID- 29575128
TI  - Synchronous mantle cell lymphoma and lung adenocarcinoma presenting in a pleural
      effusion: A rare tumour combination and a potential pitfall of cytodiagnosis.

PMID- 29575127
TI  - Assessing the release of copper from nanocopper-treated and conventional copper
      treated lumber into marine waters II: Forms and bioavailability.
AB  - One application of nanocopper is as a wood-preserving pesticide in pressure
      treated lumber. Recent research has shown that pressure-treated lumber amended
      with micronized copper azole (MCA), which contains nanosized copper, releases
      copper under estuarine and marine conditions. The form of copper released (i.e.,
      ionic, nanocopper [1-100 nm in size]) is not fully understood but will affect the
      bioavailability and toxicity of the metal. In the present study, multiple lines
      of evidence, including size fractionation, ion-selective electrode
      electrochemistry, comparative toxicity, and copper speciation were used to
      determine the form of copper released from lumber blocks and sawdust. The results
      of all lines of evidence supported the hypothesis that ionic copper was released
      from MCA lumber and sawdust, with little evidence that nanocopper was released.
      For example, copper concentrations in size fractionations of lumber block aqueous
      leachates including unfiltered, 0.1 MUm, and 3 kDa were not significantly
      different, suggesting that the form of copper released was in the size range
      operationally defined as dissolved. These results correlated with the ion
      selective electrode data which detects only ionic copper. In addition,
      comparative toxicity testing resulted in a narrow range of median lethal
      concentrations (221-257 MUg/L) for MCA lumber blocks and CuSO4 . We conclude that
      ionic copper was released from the nanocopper pressure-treated lumber under
      estuarine and marine conditions. Environ Toxicol Chem 2018;37:1969-1979.
      Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US
      government work and, as such, is in the public domain in the United States of
      America.

PMID- 29575129
TI  - The Generation of Diazo Compounds in Continuous-Flow.
AB  - Toxic, cancerogenic and explosive-these attributes are typically associated with
      diazo compounds. Nonetheless, diazo compounds are nowadays a highly demanded
      class of reagents for organic synthesis, yet the concerns with regards to safe
      and scalable transformations of these compounds are still exceptionally high.
      Lately, the research area of the continuous-flow synthesis of diazo compounds
      attracted significant interest and a whole variety of protocols for their "on
      demand" preparation have been realized to date. This concept article focuses on
      the recent developments using continuous-flow technologies to access diazo
      compounds; thus minimizing risks and hazards when working with this particular
      class of compounds. In this article we discuss these concepts and highlight
      different pre-requisites to access and to perform downstream functionalization
      reaction.

PMID- 29575130
TI  - Mitochondrial inhibitory factor protein 1 attenuates coupling factor 6-induced
      aging signal.
AB  - Coupling factor 6 (CF6) forces a counter-clockwise rotation of plasma membrane F1
      Fo complex, resulting in proton import and accelerated aging. Inhibitory factor
      peptide 1 (IF1) suppresses a unidirectional counter-clockwise rotation of F1 Fo
      complex without affecting ATP synthesis. We tested the hypothesis that IF1 may
      attenuate CF6-induced aging signaling in CF6-overexpressing transgenic (TG)
      cells. In IF1-GFP overexpressing wild type (WT) cells, the diffuse peripheral
      staining of tubular mitochondria was observed with a dense widely distributed
      network around the nucleus. In TG cells, however, the only peri-nuclear network
      of fragmented mitochondria was observed at 24 h, but it was developed to a widely
      distributed mitochondrial network of tubular mitochondria at 72 h. TG cells
      displayed aging hallmarks of telomere attrition, epigenetic alterations,
      defective proteostasis, and genomic instability with a decrease in emerin and
      lamin and loss of heterochromatin. IF1 induction rescued TG cells from telomere
      attrition, expression of genomic instability with the increase in emerin and
      lamin, and that of epigenetic alterations with recovery of heterochromatin. In
      defective proteostasis, IF1 induction restored a potent peri-nuclear staining of
      autolysosomes compared with the baseline weak staining. The decrease in Atg7 was
      restored, whereas the increase in P62 was abolished. We conclude that genetic
      disruption of proton signals by IF1 induction suppressed CF6-induced expression
      of aging hallmarks such as telomere attrition, epigenetic alterations, defective
      proteostasis, and genomic instability. Given the widespread biological actions of
      CF6, the physiological and pathological actions of IF1 may be complex.

PMID- 29575131
TI  - Anticoagulation, bleeding, and clotting at donor plasmapheresis.
AB  - This article is based on a question of a colleague from North America how
      coagulation could be triggered between a donor's arm and a fistula needle during
      plasma donation (synonymous with donor plasmapheresis). The technique of
      venipuncture and citrate anticoagulation are described. Uncommon and rare
      problems such as prolonged bleeding, scarring, and thrombosis in plasma donors
      are discussed. If venous puncture and citrate: blood flow ratio at 1:16 are
      correctly performed, however, there will be no anticoagulation abnormalities due
      to plasma donation.

PMID- 29575132
TI  - Complex formation dynamics of native and mutated pyrin's B30.2 domain with
      caspase-1.
AB  - Pyrin protein is the product of the MEFV gene, mutations in which cause
      manifestation of familial Mediterranean fever (FMF). Functions of pyrin are not
      completely clear. The secondary structure of the pyrin is represented with four
      domains and two motifs. Mutations p.M680I, p.M694V, p.M694I, p.K695R, p.V726A,
      and p.A744S, which are located in the B30.2 domain of pyrin protein, are
      responsible for manifestation of the most common and severe forms of FMF. All the
      domains and the motifs of pyrin, are directly or indirectly, involved in the
      protein-protein interaction with proteins of apoptosis and regulate the cascade
      of inflammatory reactions, which is impaired due to pyrin mutations. It is well
      known, that malfunction of the pyrin-caspase-1 complex is the main reason of
      inflammation during FMF. Complete tertiary structure of pyrin and the effects of
      mutations in it are experimentally not studied yet. The aim of this study was to
      identify possible effects of the abovementioned mutations in the B30.2 domain
      tertiary structure and to determine their potential consequences in formation of
      the B30.2-caspase-1 complex. Using in silico methods, it was found, that these
      mutations led to structural rearrangements in B30.2 domain tertiary structure,
      causing shifts of binding sites and altering the interaction energy between B30.2
      and caspase-1.

PMID- 29575133
TI  - Gemcitabine induces apoptosis and autophagy via the AMPK/mTOR signaling pathway
      in pancreatic cancer cells.
AB  - Gemcitabine (GEM)-based chemotherapy is a commonly used treatment for pancreatic
      cancer. However, acquired drug resistance, a major problem in pancreatic cancer
      treatment, causes a reduction in the survival rate of patients with cancer. In
      this study, we attempted to reveal the molecular mechanism of GEM resistance. Our
      data showed that GEM treatment inhibits cell growth, induces apoptosis, and
      activates autophagy via the AMP-activated protein kinase (AMPK) pathway. The
      combination of GEM treatment and AMPK knockdown resulted in a dramatic increase
      of apoptosis and inhibition of autophagy. Additionally, inhibition of mammalian
      target of Rapamycin induced autophagy. Our findings show the potential
      therapeutic implications of the combined treatment with GEM and AMPK inhibitors
      for pancreatic cancer.

PMID- 29575134
TI  - Glucose alert system improves health professional responses to adverse glycaemia
      and reduces the number of hyperglycaemic episodes in non-critical care
      inpatients.
AB  - AIM: To investigate the effect of a novel glucose alert system, comprising the
      Melbourne Glucose Alert Pathway and glucose-alert-capable networked blood glucose
      meters, on nursing and hospital medical officer responses to adverse glycaemia.
      METHODS: A prospective, pre- and post-observational study was undertaken in non
      critical care wards of a tertiary hospital over 4 months (n=148 or 660 patient
      days). The intervention consisted of two components designed to promote a
      consistent staff response to blood glucose measurements: (1) a clinical
      escalation pathway, the Melbourne Glucose Alert Pathway, and (2) networked blood
      glucose meters, which provide a visual alert for out-of-range blood glucose
      measurement. All consecutive inpatients with diabetes were assessed for diabetes
      management and capillary blood glucose. The primary outcome was documented
      nursing and medical staff action in response to episodes of adverse glycaemia
      (blood glucose >15 mmol/l or <4 mmol/l). Secondary outcomes consisted of
      glycaemic measures. RESULTS: In response to episodes of adverse glycaemia,
      nursing action increased (proportion with nursing action: 45% to 73%; P<0.001),
      and medical action increased (proportion with medical action: 49% to 67%;
      P=0.011) with the glucose alert system in place. Patient-days with hyperglycaemia
      (any blood glucose value >15 mmol/l: 24% vs 16%; P=0.012) and patient-days with
      mean blood glucose >15 mmol/l (7.4% vs 2.6%; P=0.005) decreased. There was no
      difference in hypoglycaemia incidence. CONCLUSIONS: Use of a novel glucose alert
      system improved health professional responses to adverse glycaemia and decreased
      hyperglycaemia in the hospital setting.

PMID- 29575135
TI  - Comparison of the Diagnostic Efficacy of Ultrasound-Guided Core Needle Biopsy
      With 18- Versus 20-Gauge Needles for Thyroid Nodules.
AB  - OBJECTIVES: To compare the diagnostic efficacy, complication rate, and core
      needle biopsy (CNB) specimen yield in 18- versus 20-gauge ultrasound (US)-guided
      CNB for diagnosis of thyroid nodules. METHODS: We included 81 consecutive thyroid
      nodules with US-guided biopsy by a 20-gauge core needle and 86 consecutive
      thyroid nodules with US-guided biopsy by an 18-gauge core needle during 2 years.
      The rate of inconclusive results, including nondiagnostic or atypia/follicular
      lesion of undetermined significance, was compared. The diagnostic performance for
      malignancy was assessed in nodules with a final diagnosis. The complication rate
      and CNB specimen yield were also compared. RESULTS: Eighteen-gauge CNB showed a
      lower rate of nondiagnostic results (1.2% versus 8.6%; P = .024) than 20-gauge
      CNB; however, the rates of atypia/follicular lesion of undetermined significance
      and inconclusive results were not significantly different between the groups (P >
      .05). In addition, 18-gauge CNB showed higher sensitivity (75.0% versus 66.7%), a
      higher negative predictive value (83.9% versus 75.9%), and higher accuracy (78.3%
      versus 74.4%) for detecting malignancy than 20-gauge CNB, although the results
      did not achieve statistical significance. No major complications occurred in
      either of the CNB groups. The 18-gauge needle group had significantly fewer CNBs
      and larger specimen diameters (P < .001). CONCLUSIONS: Core needle biopsy with an
      18-gauge needle could be more effective for the diagnosis of thyroid nodules than
      CNB with a 20-gauge needle.

PMID- 29575136
TI  - Diagnosis of pneumocystis pneumonia in a 2-year-old King Charles Cavalier Spaniel
      using the polymerase chain reaction.
AB  - A 2-year-old, female spayed, King Charles Cavalier Spaniel was presented for
      evaluation of dyspnea, inappetence, and lethargy. Thoracic radiographs revealed a
      moderate diffuse interstitial lung pattern affecting the perihilar and
      caudodorsal lung fields, and an echocardiogram revealed severe pulmonary
      hypertension. A bronchoalveolar lavage (BAL) was performed, and cytology revealed
      mixed inflammation with cysts and trophozoites consistent with Pneumocystis.
      Pneumocystis infection was later confirmed with PCR. To the author's knowledge,
      this report represents the first case of canine pneumocystis pneumonia diagnosed
      antemortem with PCR from a BAL sample. Pneumocystis represents an important, but
      uncommon cause of afebrile pneumonia in immunosuppressed dogs.

PMID- 29575137
TI  - Preparation of canine C-reactive protein serum reference material: A feasibility
      study.
AB  - BACKGROUND: The availability of a species-specific reference material is
      essential for the harmonization of results obtained in different laboratories by
      different methods. OBJECTIVES: We describe the preparation of a canine C-reactive
      protein (cCRP) serum reference material containing purified cCRP stabilized in a
      serum matrix. The material can be used by manufacturers to assign values to their
      calibrator and control materials. METHODS: The serum matrix was obtained using
      blood collected from healthy dogs, stabilized and submitted for a delipidation
      process. The reference material was prepared by diluting purified cCRP in the
      serum matrix containing 1.0 mol/L HEPES buffer, 3.0 mmol/L calcium chloride,
      80,000 kUI/L aprotinin, and 1.0 mmol/L benzamidine hydrochloride monohydrate at a
      pH of 7.2, and dispensing (0.5 mL) the matrix into vials that were then frozen.
      RESULTS: The pilot batch of 200 vials was shown to be homogeneous and stable
      after a stability study at various temperatures and over a total time of 110
      days. The prepared material was submitted to an assignment value study. Eight
      laboratories from different European countries participated by using the same
      reagents for an immunoturbidimetric method adapted for different analyzers. The
      obtained cCRP concentration in the reference material was 78.5 mg/L with an
      expanded uncertainty (k = 2) of 4.2 mg/L. CONCLUSIONS: Canine C-reactive protein
      serum reference material has been produced that allows harmonization of results
      obtained by different methods and different laboratories, thus reducing the
      possibility of errors and misunderstandings.

PMID- 29575138
TI  - Letter to the Editor: what is implied by the term biopsy?

PMID- 29575139
TI  - Erratum.

PMID- 29575140
TI  - Validation of a paraoxon-based method for measurement of paraoxonase (PON-1)
      activity and establishment of RIs in horses.
AB  - BACKGROUND: Paraoxonase-1 (PON-1) is an antioxidant compound that is considered a
      negative acute phase protein. No information on the analytic performance of the
      paraoxon method for measuring PON-1 in horse serum is available. OBJECTIVES: The
      aim of this study was to validate a paraoxon-based method to measure PON-1 in
      horses and to establish RIs in healthy horses and foals. METHODS: Horses and
      foals classified as healthy after physical examination and routine biochemistry
      were used in the study. Serum PON-1 activity was measured with an automated
      spectrophotometer and an enzymatic method validated in other species. After the
      analytic validation (precision, accuracy, interference studies), RIs were
      determined using the Reference Value Advisor software. The possible sex-, age-,
      and breed-related differences were statistically investigated. RESULTS: The
      healthy study population included 120 horses and 55 foals. The paraoxon-based
      method was precise (CVs < 4.0%) and accurate (P < .001 in linearity under
      dilution and spike-recovery testing) but was affected by interference from mild
      bilirubinemia, severe lipemia, and hemoglobinemia. The RIs recorded in the whole
      population were 38.1-80.8 U/mL. According to the Harris and Boyd test, it would
      be advisable to use separate RIs only for adult females and for Warmblood and
      Trotter adults. CONCLUSIONS: This study demonstrated that the analytic
      performances of the paraoxon-based method for measurement of PON-1 in horses are
      acceptable. The PON-1 activity is lower in horses than in other domestic species.
      These results may provide a basis for further studies designed to establish
      whether healthy and sick horses can be correctly classified by using the PON-1
      assay.

PMID- 29575142
TI  - Plasma biochemistry RIs and age effect in European Strigiformes.
AB  - BACKGROUND: Blood biochemistry and hematology are essential in the laboratory
      diagnosis of disease. In Strigiformes, little information regarding reference
      values and influence of different preanalytic factors is available, while age is
      known to have an effect on some biochemistry analytes, especially in early life
      characterized by a rapid growth rate and increase in body mass. OBJECTIVE: The
      objective of this study was to determine baseline data for 29 blood biochemistry
      variables in 5 species of Iberian Strigiformes assigned to different age classes.
      METHODS: Healthy nocturnal birds living in wildlife health centers of Catalonia,
      Northeastern Spain were assigned to different age classes (chicks, juveniles,
      adults where possible and available) and their blood was collected and analyzed
      for different standard biochemistry variables. Species included Tawny owls,
      Little owls, Long-eared owls, Scop owls, and Barn owls. RESULTS: A total of 276
      clinically healthy animals were sampled, including between 179 chicks, 52
      juveniles, and 45 adults. The RIs of cholesterol, albumin, and osmolality were
      the only variables that did not show interspecific variability. Common trends
      between age class groups were observed in 4 species. Phosphorus and calcium
      concentrations and ALP activities decreased with increasing age, while
      concentrations of sodium and gamma-globulins tended to increase in the Strigidae
      family. Differences were concentrated in chicks and no differences were observed
      between juveniles and adults in any variable. CONCLUSIONS: Our results
      demonstrate the importance of defining biochemical RIs specific for certain age
      classes.

PMID- 29575143
TI  - Blood gas and serum biochemical RIs for healthy newborn Murrah buffaloes (Bubalus
      bubalis).
AB  - BACKGROUND: There is a lack of published work on RIs for newborn buffaloes.
      Establishing blood gas and serum biochemical RIs for newborn buffaloes is
      important for monitoring health. OBJECTIVES: This study establishes blood gas and
      serum biochemical RIs of newborn buffaloes. METHODS: Twenty-eight newborn
      buffaloes, 10-30 days old, were selected. Thirty blood biochemical variables were
      analyzed. The Anderson-Darling test was used to assess the normality of the
      distribution. The Dixon test and the Tukey test were used to identify outliers.
      The RI and 90% CI were determined using standard and robust methods and the Box
      Cox transformation. RESULTS: A total of 30 RIs for healthy buffalo calves have
      been reported in this study. RIs for blood gas variables were reported for pH,
      partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ),
      saturation of O2 (SO2 ), bicarbonate (cHCO3- ), base excess (BE), total carbon
      dioxide (ctCO2 ), and anion gap (AG). RIs for serum biochemical variables were
      reported for glucose (GLU), direct bilirubin (DB), total bilirubin (TB), AST,
      ALP, GGT, CK, LDH, creatinine (CREA), urea, cholesterol (CHOL), triglycerides
      (TG), Ca, P, Mg, Na, K, iCa, Cl, iron, total protein (TP), and albumin (ALB).
      CONCLUSIONS: This is the first reported study covering complete serum chemistry
      and blood gas RIs for healthy 1-month-old Murrah buffaloes.

PMID- 29575144
TI  - Combined and breed-specific RIs for hematologic, biochemical, and hormonal
      analytes in Chios and Florina adult rams.
AB  - BACKGROUND: Clinical pathology investigations are essential to evaluate the
      health status and practice management of ruminants. Appropriate and accurate RIs
      are required for the interpretation of laboratory results. Despite substantial
      phenotypic differences and management-related disparities between male and female
      sheep, RIs in rams are sparse and limited by small reference populations and
      outdated methods. OBJECTIVES: The purpose of this study was to establish RIs for
      hematologic, biochemical, and hormonal analytes in adult rams using controlled
      preanalytic and analytic procedures, and to investigate whether breed-dependent
      partitioning of RIs is required. METHODS: Reference individuals were selected by
      a direct a priori method. Blood was collected from 128 healthy adult rams
      representing 2 Greek breeds (64 Chios and 64 Florina). Hematologic analysis was
      performed on the Advia 120, while differential WBC counts were manually performed
      on Giemsa-stained blood smears. Flexor E, AVL 9180 Electrolyte Analyzer, and
      Immulite 1000 were used for biochemical and hormonal analyses, respectively.
      Combined and breed-specific RIs were calculated using nonparametric and robust
      methods, respectively. RESULTS: Five outliers were detected based on laboratory
      results. Partitioning of RIs, based on both statistical and nonstatistical
      criteria, was recommended for some of the analytes. CONCLUSIONS: The RIs are in
      some agreement with those in the literature. The observed differences may be
      attributed to preanalytic and analytic factors. The RIs determined in this study
      can be used as a guide for the interpretation of laboratory results in rams and
      can potentially be adopted by veterinary laboratories, provided that similar
      equipment and reagents are used.

PMID- 29575145
TI  - A neoplasm artfully unveils its origin in cytology: Karkinos emerging from the
      deep.

PMID- 29575146
TI  - Evaluation of inhibitors for development of a selective medium for isolation of
      Leptospira spp. from clinical samples.
AB  - : This study was conducted to develop a selective medium for the detection of
      Leptospira spp. in clinical samples. Serovars of Leptospira spp., environmental
      bacteria and the fungus from contaminated cultures of patients with suspected
      leptospirosis were inoculated into EMJH medium containing amphotericin B, 5
      fluorouracil (5-FU), furazolidone and neomycin used singly or combined. Medium
      with 5-FU at the concentration of 200 MUg ml-1 did not show any inhibitory effect
      against the fungus, Gram-negative bacilli and any of the leptospira strains
      except serovar Pyrogenes. The highest concentration of neomycin and furazolidone
      that did not inhibit the growth of leptospires was 4 MUg ml-1 . All strains of
      Leptospira spp. grew on 5-FU (100 MUg ml-1 ) in combination with neomycin (4 MUg
      ml-1 ) and on 5-FU (100 MUg ml-1 ) in combination with furazolidone (4 MUg ml-1
      ). The highest concentration of amphotericin B (500 MUg ml-1 ) that inhibited the
      growth of the fungus also inhibited the bacteria and most of serovars of
      Leptospira spp. The most effective antibiotic combinations that inhibited the
      majority of environmental bacteria growth without affecting leptospiral growth
      were EMJH with 5-FU (100 MUg ml-1 ) in combination with neomycin (4 MUg ml-1 ).
      In conclusion, these findings will help the development of new selective media to
      isolate leptospires. SIGNIFICANCE AND IMPACT OF THE STUDY: Leptospirosis is one
      of the most widespread zoonotic diseases in the world. Since certain serovars are
      often associated with the symptoms and severity of the disease, the isolation and
      identification of the leptospires usually permits the prediction of sources of
      infection. Attempts to isolate Leptospira spp. from clinical specimens are often
      frustrated by overgrowth of the slow-growing bacteria by more rapidly growing
      contaminants. In this study, we evaluated selective agents to develop a new
      selective medium to isolate leptospires. The results demonstrated that the
      association of drugs in concentrations that allowed the growth of leptospires is
      to be more effective in inhibiting bacterial contaminants.

PMID- 29575147
TI  - The Expanding Utility of Rhodium-Iminocarbenes: Recent Advances in the Synthesis
      of Natural Products and Related Scaffolds.
AB  - Rhodium-iminocarbenes that are derived from N-sulfonyl-1,2,3-triazoles have
      become an important class of reactive species and useful intermediates in organic
      synthesis. Over the last several years, many practical and versatile approaches
      involving rhodium-iminocarbene intermediates to synthetically challenging
      molecules (scaffolds) have been developed. This Minireview mainly summarizes the
      recent advance of rhodium-iminocarbene involved reactions in the synthesis of
      natural products and their related scaffolds by the end of 2017. Several
      applications in important pharmaceuticals are documented as well.

PMID- 29575148
TI  - Charge-Trapping-Induced Non-Ideal Behaviors in Organic Field-Effect Transistors.
AB  - Organic field-effect transistors (OFETs) with impressively high hole mobilities
      over 10 cm2 V-1 s-1 and electron mobilities over 1 cm2 V-1 s-1 have been reported
      in the past few years. However, significant non-ideal electrical characteristics,
      e.g., voltage-dependent mobilities, have been widely observed in both small
      molecule and polymer systems. This issue makes the accurate evaluation of the
      electrical performance impossible and also limits the practical applications of
      OFETs. Here, a semiconductor-unrelated, charge-trapping-induced non-ideality in
      OFETs is reported, and a revised model for the non-ideal transfer characteristics
      is provided. The trapping process can be directly observed using scanning Kelvin
      probe microscopy. It is found that such trapping-induced non-ideality exists in
      OFETs with different types of charge carriers (p-type or n-type), different types
      of dielectric materials (inorganic and organic) that contain different functional
      groups (?OH, ?NH2 , ?COOH, etc.). As fas as it is known, this is the first report
      for the non-ideal transport behaviors in OFETs caused by semiconductor
      independent charge trapping. This work reveals the significant role of dielectric
      charge trapping in the non-ideal transistor characteristics and also provides
      guidelines for device engineering toward ideal OFETs.

PMID- 29575149
TI  - Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat
      accumulation.
AB  - The accumulation of fatty acids in the liver associated with obesity condition is
      also known as nonalcoholic fatty liver disease (NAFLD). The impaired fat
      oxidation in obesity condition leads to increased hepatic fat accumulation and
      increased metabolic syndrome risk. On the other hand, physical exercise has been
      demonstrated as a potent strategy in the prevention of NAFLD. Also, these
      beneficial effects of exercise occur through different mechanisms. Recently, the
      Cdc2-like kinase (CLK2) protein was associated with the suppression of fatty acid
      oxidation and hepatic ketogenesis. Thus, obese animals demonstrated elevated
      levels of hepatic CLK2 and decreased fat acid oxidation. Here, we explored the
      effects of chronic physical exercise in the hepatic metabolism of obese mice.
      Swiss mice were distributed in Lean, Obese (fed with high-fat diet during 16
      weeks) and Trained Obese group (fed with high-fat diet during 16 weeks and
      exercised (at 60% exhaustion velocity during 1 h/5 days/week) during 8 weeks. In
      our results, the obese animals showed insulin resistance, increased hepatic CLK2
      content and increased hepatic fat accumulation compared to the Lean group.
      Otherwise, the chronic physical exercise improved insulin resistance state,
      prevented the increased CLK2 in the liver and attenuated hepatic fat
      accumulation. In summary, these data reveal a new protein involved in the
      prevention of hepatic fat accumulation after chronic physical exercise. More
      studies can evidence the negative role of CLK2 in the control of liver
      metabolism, contributing to the improvement of insulin resistance, obesity, and
      type 2 diabetes.

PMID- 29575151
TI  - Long non-coding RNA NEAT1 mediates the toxic of Parkinson's disease induced by
      MPTP/MPP+ via regulation of gene expression.
AB  - Parkinson's disease (PD) is a result of the loss of dopaminergic neurons in the
      substantia nigra and is expected to increase the economic burden on patients'
      families and societies. NEAT1, a long non-coding RNA, is known as a cancer
      related gene, however, the role of it in PD remains unclear. The aims of this
      study are to detect the NEAT1-mediated effects in PD and explore the mechanism of
      NEAT1 in PD. One group (n = 6) of C57BL/6 model mice were intraperitoneal
      injected with 1-Methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP), while another
      group (n = 6) was treated with saline and served as control. Human neuroblastoma
      cell line SH-SY5Y was pretreated with 1-Methyl-4-phenylpyridinium (MPP+). Cell
      viability and apoptosis, as well as gene expression with different treatments
      were examined. Up-regulated NEAT1 was found in MPTP-induced PD mice. Moreover,
      the NEAT1 expression was positively correlated with the concentration of MPP+. In
      SH-SY5Y cells stimulated by MPP+, NEAT1 knockdown dramatically promoted cell
      viability and suppressed cell apoptosis. Additionally, down-regulation of NEAT1
      also decreased the ratio of Bax/Bcl-2, the activity of caspase-3, as well as the
      expression of alpha-synuclein. Moreover, alpha-synuclein overexpression could
      significantly reverse the increase in cell viability and the decrease in cell
      apoptosis induced by NEAT1 knockdown. The results suggested that the knockdown of
      NEAT1 will have a protective effect on MPTP-induced PD mice. The mechanism may be
      related to the dysregulation of alpha-synuclein.

PMID- 29575150
TI  - Diagnostic value of serum galactomannan, (1,3)-beta-d-glucan, and Aspergillus
      fumigatus-specific IgA and IgG assays for invasive pulmonary aspergillosis in non
      neutropenic patients.
AB  - Detection of serum galactomannan (GM) and (1,3)-beta-d-glucan (BG) is considered
      useful for non-culture diagnosis of invasive pulmonary aspergillosis (IPA) in
      neutropenic patients. Only few studies evaluated these seromarkers in non
      neutropenic patients suspected of having IPA. The aim of this study was to
      evaluate both tests together with the Aspergillus fumigatus-specific serum IgG
      and IgA (IgAG) test for serological IPA diagnosis in non-neutropenic patients.
      Sera from 87 patients suspected of having IPA were retrospectively analysed.
      Patients were categorised into groups of proven IPA (n = 10), putative IPA (n =
      31) and non-IPA colonisation (n = 46). When the GM, BG and IgAG assays were used
      for patients included in the study, the sensitivity/specificity/positive
      predictive value (PPV)/negative predictive value (NPV) were
      48.8%/91.3%/83.3%/66.7%, 82.9%/73.9%/73.9%/82.9% and 75.6%/95.7%/93.9%/81.5%,
      respectively. Thus, the highest specificity and PPV were confirmed for the IgAG
      assay. Improvements in the sensitivity and NPV were achieved by "at least one
      positive" analysis with the GM and BG assays, with the
      sensitivity/specificity/PPV/NPV values being 85.0%/69.6%/71.4%/84.2%.
      Nevertheless, the highest sensitivity and NPV were achieved by the "at least one
      positive" analysis combining the GM, BG and IgAG tests (97.6% and 96.8%,
      respectively). The involvement of the IgAG assay could improve IPA diagnosis in
      non-neutropenic patients by increasing the sensitivity and NPV when combined with
      the GM or BG assays. Furthermore, improvement was achieved by combining the GM,
      BG and IgAG assays using the "at least one positive test" strategy, especially if
      doubt exists.

PMID- 29575152
TI  - Assessing the release of copper from nanocopper-treated and conventional copper
      treated lumber into marine waters I: Concentrations and rates.
AB  - Little is known about the release of metal engineered nanomaterials (ENMs) from
      consumer goods, including lumber treated with micronized copper. Micronized
      copper is a recent form of antifouling wood preservative containing nanosized
      copper particles for use in pressure-treated lumber. The present study
      investigated the concentrations released and the release rate of total copper
      over the course of 133 d under freshwater, estuarine, and marine salinity
      conditions (0, 1, 10, and 300/00) for several commercially available pressure
      treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m3 , alkaline
      copper quaternary (ACQ) at 0.30 and 9.6 kg/m3 , and chromated copper arsenate
      (CCA) at 40 kg/m3 . Lumber was tested as blocks and as sawdust. Overall, copper
      was released from all treated lumber samples. Under leaching conditions, total
      release ranged from 2 to 55% of the measured copper originally in the lumber,
      with release rate constants from the blocks of 0.03 to 2.71 (units per day).
      Generally, measured release and modeled equilibrium concentrations were
      significantly higher in the estuarine conditions compared with freshwater or
      marine salinities, whereas rate constants showed very limited differences between
      salinities. Furthermore, organic carbon was released during the leaching and
      demonstrated a significant relationship with released copper concentrations as a
      function of salinity. The results indicate that copper is released into
      estuarine/marine waters from multiple wood treatments including lumber amended
      with nanoparticle-sized copper. Environ Toxicol Chem 2018;37:1956-1968. Published
      2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government
      work and, as such, is in the public domain in the United States of America.

PMID- 29575153
TI  - Validation of the systematic scoring of immunohistochemically stained tumour
      tissue microarrays using QuPath digital image analysis.
AB  - AIMS: Output from biomarker studies involving immunohistochemistry applied to
      tissue microarrays (TMA) is limited by the lack of an efficient and reproducible
      scoring methodology. In this study, we examine the functionality and
      reproducibility of biomarker scoring using the new, open-source, digital image
      analysis software, QuPath. METHODS AND RESULTS: Three different reviewers, with
      varying experience of digital pathology and image analysis, applied an agreed
      QuPath scoring methodology to CD3 and p53 immunohistochemically stained TMAs from
      a colon cancer cohort (n = 661). Manual assessment was conducted by one reviewer
      for CD3. Survival analyses were conducted and intra- and interobserver
      reproducibility assessed. Median raw scores differed significantly between
      reviewers, but this had little impact on subsequent analyses. Lower CD3 scores
      were detected in cases who died from colorectal cancer compared to control cases,
      and this finding was significant for all three reviewers (P-value range = 0.002
      0.02). Higher median p53 scores were generated among cases who died from
      colorectal cancer compared with controls (P-value range = 0.04-0.12). The ability
      to dichomotise cases into high versus low expression of CD3 and p53 showed
      excellent agreement between all three reviewers (kappa score range = 0.82-0.93).
      All three reviewers produced dichotomised expression scores that resulted in very
      similar hazard ratios for colorectal cancer-specific survival for each biomarker.
      Results from manual and QuPath methods of CD3 scoring were comparable, but QuPath
      scoring revealed stronger prognostic stratification. CONCLUSIONS: Scoring of
      immunohistochemically stained tumour TMAs using QuPath is functional and
      reproducible, even among users of limited experience of digital pathology images,
      and more accurate than manual scoring.

PMID- 29575154
TI  - Escherichia coli transcription factor NusG binds to 70S ribosomes.
AB  - Transcription and translation are coupled processes in bacteria. A role of
      transcription elongation cofactor NusG in coupling has been suggested by in vitro
      structural studies. NMR revealed association of the NusG carboxy-terminal domain
      with S10 (NusE), implying a direct role for NusG as a bridge linking RNAP and the
      lead ribosome. Here we present the first in vitro and in vivo evidence of full
      length NusG association with mature 70S ribosomes. Binding did not require
      accessory factors in vitro. Mutating the NusG:S10 binding interface at NusG F165
      or NusE M88 and D97 residues weakened NusG:S10 association in vivo and completely
      abolished it in vitro, supporting the specificity of this interaction. Mutations
      in the binding interface increased sensitivity to chloramphenicol. This phenotype
      was suppressed by rpoB*35, an RNAP mutation that reduces replisome-RNAP clashes.
      We propose that weakened NusG:S10 interaction leads to uncoupling when
      translation is inhibited, with resulting RNAP backtracking, replication blocks
      and formation of lethal DNA double-strand breaks.

PMID- 29575156
TI  - The overexpression of TcAP1 endonuclease confers resistance to infective
      Trypanosoma cruzi trypomastigotes against oxidative DNA damage.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease survives to DNA damage
      generated by ROS/RNS inside to their different hosts. In recent eukaryotes,
      oxidative DNA damage is repaired mainly by the Base Excision Repair (BER)
      pathway, being essential the apurinic/apyrimidinic endonuclease activity. Using a
      pTREX-gfp vector, the nucleotide sequence that encodes T. cruzi AP endonuclease
      TcAP1 (orthologue of human APE1) and a putative TcAP1 dominant negative
      (TcAP1DN), were transfectedand expressed in T. cruzi epimastigotes. TcAP1-GFP and
      TcAP1DN-GFP were expressed in those modified epimastigotes and found in the
      parasite nucleus. The endonucleases were purified under native conditions and the
      AP endonuclease activity was evaluated. While TcAP1 presents the expected AP
      endonuclease activity TcAP1DN does not. Moreover, TcAP1DN partially inhibits in
      vitro TcAP1 enzymatic activity. Transfected epimastigotes expressing TcAP1-GFP
      and TcAP1DN-GFP were differentiated to infective trypomastigotes. The infective
      parasites maintained both proteins (TcAP1-GFP and TcAP1DN-GFP) in the nucleus.
      The overexpression of TcAP1-GFP in epimastigotes and trypomastigotes increases
      the viability of both parasite forms when exposed to oxidative stress while the
      expression of TcAP1DN-GFP did not show any in vivo inhibitory effect, suggesting
      that endogenous TcAP1 constitutive expression overcomes the TcAP1DN inhibitory
      activity. Our results show that TcAP1 is important for trypomastigote survival
      under oxidative conditions similar to those found in infected mammalian cells,
      then increasing its permanence in the infected cells and the possibility of
      development of Chagas disease.

PMID- 29575155
TI  - Atypical audiovisual temporal function in autism and schizophrenia: similar
      phenotype, different cause.
AB  - Binding across sensory modalities yields substantial perceptual benefits,
      including enhanced speech intelligibility. The coincidence of sensory inputs
      across time is a fundamental cue for this integration process. Recent work has
      suggested that individuals with diagnoses of schizophrenia (SZ) and autism
      spectrum disorder (ASD) will characterize auditory and visual events as
      synchronous over larger temporal disparities than their neurotypical
      counterparts. Namely, these clinical populations possess an enlarged temporal
      binding window (TBW). Although patients with SZ and ASD share aspects of their
      symptomatology, phenotypic similarities may result from distinct etiologies. To
      examine similarities and variances in audiovisual temporal function in these two
      populations, individuals diagnosed with ASD (n = 46; controls n = 40) and SZ (n =
      16, controls = 16) completed an audiovisual simultaneity judgment task. In
      addition to standard psychometric analyses, synchrony judgments were assessed
      using Bayesian causal inference modeling. This approach permits distinguishing
      between distinct causes of an enlarged TBW: an a priori bias to bind sensory
      information and poor fidelity in the sensory representation. Findings indicate
      that both ASD and SZ populations show deficits in multisensory temporal acuity.
      Importantly, results suggest that while the wider TBWs in ASD most prominently
      results from atypical priors, the wider TBWs in SZ results from a trend toward
      changes in prior and weaknesses in the sensory representations. Results are
      discussed in light of current ASD and SZ theories and highlight that different
      perceptual training paradigms focused on improving multisensory integration may
      be most effective in these two clinical populations and emphasize that similar
      phenotypes may emanate from distinct mechanistic causes.

PMID- 29575157
TI  - Finding meaning in suffering?-Meaning making and psychological adjustment over
      the course of a breast cancer disease.
AB  - This study aimed to explore individual meaning systems in the course of a breast
      cancer disease to test the assumed positive relation between meaning and well
      being and to investigate the relationship between post-traumatic growth and well
      being. A total of 65 patients with breast cancer were examined 1 year after
      initial treatment and another year follow-up. Questionnaires addressed meaning in
      life (MLQ), anxiety and depression (HADS), satisfaction with life (SWLS), health
      related quality of life (EQ-5D, EORTC) and post-traumatic growth (PTGI). Personal
      meaning systems were assessed using a qualitative method. In the personal meaning
      systems with well-being and relationships as the most frequently named meaning
      categories, the experienced gains far outweigh the losses sustained as a result
      of the disease. A stronger sense of meaning was related to lower levels of
      anxiety and depression, a higher level of satisfaction with life and better
      health-related functioning. Well-being and post-traumatic growth were mostly
      independent. Reported losses were strongly related to a poorer well-being. Cancer
      can induce a process of personal growth, and a strong sense of purpose could
      facilitate psychological adjustment. The often claimed correlation of post
      traumatic growth and a better psychological adjustment is still lacking clear
      evidence, whereas losses proofed to be crucial.

PMID- 29575158
TI  - Isolated caseous calcification of the mitral valve.

PMID- 29575159
TI  - Mapping the tandem mass spectrometric characteristics of citrulline-containing
      peptides.
AB  - RATIONALE: Protein citrullination (deimination) is a post-translational
      modification of proteins converting arginine(s) into citrulline(s).
      "Overcitrullination" could be associated with severe pathological conditions.
      Mass spectrometric analysis of modified proteins is hindered by several problems.
      A comprehensive study of the fragmentation of deiminated peptides is not yet
      available. In this paper we have made an attempt to describe the characteristics
      of these processes, based on the studies of epitope model oligopeptides derived
      from clinically relevant proteins. METHODS: Solutions of purified model peptides
      containing either one or two citrulline residues as well as their native variants
      were injected directly into the electrospray source of a high accuracy and
      resolution quadrupole-time-of-flight instrument and were analysed by tandem mass
      spectrometry using low-energy collision-induced dissociation. RESULTS: Loss of
      isocyanic acid from citrulline residues is a preferred fragmentation route for
      deiminated peptides, which yields ornithine residues in the sequence. However,
      simultaneous detection of both the isocyanic acid loss and sequence fragments is
      often compromised. A preferential cleavage site was observed between citrulline
      and any other following amino acids yielding intensive complementary b- and y
      type ions. Also, citrulline positioned at the C-termini displays a preferential
      cleavage N-terminal to this residue yielding characteristic y1 ions. These
      phenomena are described here for the first time and are referred to as the
      "citrulline effect". CONCLUSIONS: We found that the citrulline effect is very
      pronounced and could be used as a complementary tool for the confirmation of
      modification sites in addition to losses of isocyanic acids from the protonated
      molecules or from fragment ions. Low collision energy applied to peptide ions
      having partially mobile protons reveals the site of modification by generating
      specific and intensive fragments of the sequence. On the other hand, fragmenting
      precursor ions with mobile protons usually allows full sequence coverage,
      although citrulline-specific fragments may exhibit lower intensities compared to
      other fragments.

PMID- 29575160
TI  - Association of serious infections with pemphigus and pemphigoid: analysis of the
      Nationwide Inpatient Sample.
AB  - BACKGROUND: Pemphigus and pemphigoid are blistering disorders associated with
      barrier disruption, immune dysregulation and use of immunosuppressing systemic
      therapy, all of which may predispose towards serious infections. OBJECTIVES: To
      determine whether pemphigus and pemphigoid are associated with increased
      likelihood of serious infections and the impact of such infections on mortality
      and cost of care. METHODS: We analysed data from the 2002 to 2012 Nationwide
      Inpatient Sample, including a representative 20% sample of all hospitalizations
      in the US (total n = 72 108 077 adults). RESULTS: Overall, 54.6% (95% CI: 53.6
      55.6%) and 50.4% (49.0-51.8%) of inpatients with either pemphigoid or pemphigus
      had a diagnosis of serious infection, respectively, compared with 25.4% (25.2
      25.6%) in those without either diagnosis. In multivariable logistic regression
      models controlling for gender, age, race/ethnicity and insurance status,
      pemphigoid or pemphigus was associated with 26 or 21 of 48 infections examined,
      respectively. In particular, both pemphigoid and pemphigus were associated with
      higher odds of infections of the skin, bones, respiratory, gastrointestinal,
      genitourinary and central nervous system, septicaemia and antibiotic-resistant
      infections. Pemphigus was also associated with aspergillus, pharyngitis and
      Pneumocystis Carinii pneumonia. Associations of any serious infection in both
      pemphigoid and pemphigus patients were older age, non-White race, lower median
      household income, government or no insurance, higher number of chronic
      conditions, and those with a diagnosis of Cushing's syndrome, diabetes, cancer or
      autoimmune disease. The diagnosis of any serious infection vs. no infection was
      associated with increased inpatient mortality and costs in both pemphigoid
      (mortality: 7.85% vs. 2.84%; cost: $16 115 vs. $10 653) and pemphigus (mortality:
      6.78% vs. 1.88%; cost: $17 707 vs. $11 545) inpatients (P < 0.0001 for all).
      CONCLUSIONS: Adults with pemphigus or pemphigoid had increased cutaneous,
      respiratory, multi-organ and systemic infections, which were associated with
      considerable inpatient mortality and cost burden. Moreover, there were
      significant clinical and healthcare disparities with respect to infections in
      patients with pemphigus or pemphigoid.

PMID- 29575161
TI  - Single-shot spiral imaging at 7 T.
AB  - PURPOSE: The purpose of this work is to explore the feasibility and performance
      of single-shot spiral MRI at 7 T, using an expanded signal model for
      reconstruction. METHODS: Gradient-echo brain imaging is performed on a 7 T system
      using high-resolution single-shot spiral readouts and half-shot spirals that
      perform dual-image acquisition after a single excitation. Image reconstruction is
      based on an expanded signal model including the encoding effects of coil
      sensitivity, static off-resonance, and magnetic field dynamics. The latter are
      recorded concurrently with image acquisition, using NMR field probes. The
      resulting image resolution is assessed by point spread function analysis.
      RESULTS: Single-shot spiral imaging is achieved at a nominal resolution of 0.8
      mm, using spiral-out readouts of 53-ms duration. High depiction fidelity is
      achieved without conspicuous blurring or distortion. Effective resolutions are
      assessed as 0.8, 0.94, and 0.98 mm in CSF, gray matter and white matter,
      respectively. High image quality is also achieved with half-shot acquisition
      yielding image pairs at 1.5-mm resolution. CONCLUSION: Use of an expanded signal
      model enables single-shot spiral imaging at 7 T with unprecedented image quality.
      Single-shot and half-shot spiral readouts deploy the sensitivity benefit of high
      field for rapid high-resolution imaging, particularly for functional MRI and
      arterial spin labeling.

PMID- 29575162
TI  - On-line capillary electrophoresis/laser-induced fluorescence/mass spectrometry
      analysis of glycans labeled with TealTM fluorescent dye using an electrokinetic
      sheath liquid pump-based nanospray ion source.
AB  - RATIONALE: N-linked glycan analysis of recombinant therapeutic proteins, such as
      monoclonal antibodies, Fc-fusion proteins, and antibody-drug conjugates, provides
      valuable information regarding protein therapeutics glycosylation profile. Both
      qualitative identification and quantitative analysis of N-linked glycans on
      recombinant therapeutic proteins are critical analytical tasks in the biopharma
      industry during the development of a biotherapeutic. METHODS: Currently, such
      analyses are mainly carried out using capillary electrophoresis/laser-induced
      fluorescence (CE/LIF), liquid chromatography/fluorescence (LC/FLR), and liquid
      chromatography/fluorescence/mass spectrometry (LC/FLR/MS) technologies. N-linked
      glycans are first released from glycoproteins by enzymatic digestion, then
      labeled with fluorescence dyes for subsequent CE or LC separation, and LIF or MS
      detection. Here we present an on-line CE/LIF/MS N-glycan analysis workflow that
      incorporates the fluorescent TealTM dye and an electrokinetic pump-based
      nanospray sheath liquid capillary electrophoresis/mass spectrometry (CE/MS) ion
      source. RESULTS: Electrophoresis running buffer systems using ammonium acetate
      and ammonium hydroxide were developed for the negative ion mode CE/MS analysis of
      fluorescence-labeled N-linked glycans. Results show that on-line CE/LIF/MS
      analysis can be readily achieved using this versatile CE/MS ion source on common
      CE/MS instrument platforms. CONCLUSIONS: This on-line CE/LIF/MS method using
      TealTM fluorescent dye and electrokinetic pump-based nanospray sheath liquid
      CE/MS coupling technology holds promise for on-line quantitation and
      identification of N-linked glycans on recombinant therapeutic proteins.

PMID- 29575163
TI  - High-Voltage Lithium-Metal Batteries Enabled by Localized High-Concentration
      Electrolytes.
AB  - Rechargeable lithium-metal batteries (LMBs) are regarded as the "holy grail" of
      energy-storage systems, but the electrolytes that are highly stable with both a
      lithium-metal anode and high-voltage cathodes still remain a great challenge.
      Here a novel "localized high-concentration electrolyte" (HCE; 1.2 m lithium
      bis(fluorosulfonyl)imide in a mixture of dimethyl carbonate/bis(2,2,2
      trifluoroethyl) ether (1:2 by mol)) is reported that enables dendrite-free
      cycling of lithium-metal anodes with high Coulombic efficiency (99.5%) and
      excellent capacity retention (>80% after 700 cycles) of Li||LiNi1/3 Mn1/3 Co1/3
      O2 batteries. Unlike the HCEs reported before, the electrolyte reported in this
      work exhibits low concentration, low cost, low viscosity, improved conductivity,
      and good wettability that make LMBs closer to practical applications. The
      fundamental concept of "localized HCEs" developed in this work can also be
      applied to other battery systems, sensors, supercapacitors, and other
      electrochemical systems.

PMID- 29575164
TI  - Increasing specific immunoglobulin E levels correlate with the risk of
      anaphylaxis during an oral food challenge.
AB  - BACKGROUND: Oral food challenges (OFCs) are necessary to diagnose food allergies;
      however, these tests can cause anaphylaxis. Higher specific immunoglobulin E
      (sIgE) levels to causative food have been associated with a positive OFC. To
      date, no data have been found to indicate the factors associated with severe
      symptoms or anaphylaxis among challenge-positive patients. This study aimed to
      clarify the association of sIgE with causative foods and anaphylaxis during OFC
      among the whole study population and challenge-positive patients. METHODS: This
      cross-sectional study collected symptom and severity data between June 2012 and
      December 2016 during an open OFC to diagnose food allergy or confirm tolerance
      acquisition. We analyzed the risk factors for anaphylaxis during OFC. RESULTS: A
      total of 2272 cases were analyzed (median age: 3.5 years; egg: 1166 cases; milk:
      589 cases; wheat: 388 cases; and peanut: 129 cases). Among 979 challenge-positive
      patients, anaphylactic reactions were observed in 334 cases. A statistically
      significant association was observed between anaphylaxis during OFC and higher
      sIgE levels to causative foods (odds ratio: 2.71, 95% confidence interval: 1.94
      3.78, for the third compared to the first tertile, P-value for trend <.001). Only
      gastrointestinal, respiratory, cardiovascular, and neurological symptoms were
      also statistically significantly associated with higher sIgE levels to causative
      foods. CONCLUSIONS: The risk of all symptoms, except skin symptoms, during OFCs
      increased with increasing sIgE levels, and this consequently increased
      anaphylaxis during OFCs. The mechanism of how sIgE affects the prevalence of
      gastrointestinal, respiratory, cardiovascular, and neurological symptoms or
      anaphylaxis is unknown; thus, further study is required.

PMID- 29575165
TI  - Integrating the fundamentals of care framework in baccalaureate nursing
      education: An example from a nursing school in Denmark.
AB  - AIMS AND OBJECTIVES: To describe and discuss the process of integrating the
      Fundamentals of Care framework in a baccalaureate nursing education at a School
      of Nursing in Denmark. BACKGROUND: Nursing education plays an essential role in
      educating nurses to work within healthcare systems in which a demanding workload
      on nurses results in fundamental nursing care being left undone. Newly graduated
      nurses often lack knowledge and skills to meet the challenges of delivering
      fundamental care in clinical practice. To develop nursing students' understanding
      of fundamental nursing, the conceptual Fundamentals of Care framework has been
      integrated in nursing education at a School of Nursing in Denmark. DESIGN AND
      METHODS: Discursive paper using an adjusted descriptive case study design for
      describing and discussing the process of integrating the conceptual Fundamentals
      of Care Framework in nursing education. RESULTS: The process of integrating the
      Fundamentals of Care framework is illuminated through a description of the
      context, in which the process occurs including the faculty members, lectures,
      case-based work and simulation laboratory in nursing education. Based on this
      description, opportunities such as supporting a holistic approach to an evidence
      based integrative patient care and challenges such as scepticism among the
      faculty are discussed. CONCLUSION: It is suggested how integration of
      Fundamentals of Care Framework in lectures, case-based work and simulation
      laboratory can make fundamental nursing care more explicit in nursing education,
      support critical thinking and underline the relevance of evidence-based practice.
      The process relies on a supportive context, a well-informed and engaged faculty,
      and continuous reflections on how the conceptual framework can be integrated.
      RELEVANCE TO CLINICAL PRACTICE: Integrating the Fundamentals of Care framework
      can support nursing students' critical thinking and reflection on what
      fundamental nursing care is and requires and eventually educate nurses in
      providing evidence-based fundamental nursing care.

PMID- 29575166
TI  - Anatomy of medial plantar superficial branch artery perforators: Facilitation of
      medial plantar superficial branch artery perforator (MPAP) flap harvesting and
      design for finger pulp reconstruction.
AB  - BACKGROUND: Medial plantar artery perforator (MPAP) flap was proposed as proper
      option for finger pulp reconstruction. To provide the previously unavailable
      vessel information required for this small flap design, this study aimed to
      gather all necessary anatomy of MPA, MPAP, and their territories of blood supply
      to apply in clinical MPAP flap reconstruction minimizing perforator injury.
      METHODS: Dissection of 30 Thai cadaveric feet for visualizing superficial branch
      of MPA and its perforators (MPAP) using acrylic dye cannulation were performed.
      Diameter, length, number of branches, course, distributing areas of these
      vessels, and also their areas of blood supply were recorded in relation to
      specified landmarks, eg, C-MTH line; medial calcaneal tuberosity to plantar side
      of the first metatarsal head and S point; emerging point of superficial branch of
      MPA from deep fasciae into subcutaneous layer. RESULTS: Average diameter of MPA
      at its origin and total length are 1.63 +/- 0.3 and 52.8 +/- 16.1 mm,
      respectively. It provides 1-3 perforators, with an average size and length of
      0.36 +/- 0.11 and 23.2 +/- 5.47 mm, respectively. Its distribution is mostly in
      the posteromedial quadrant within 50 and 30 mm from the midpoint of C-MTH line
      and the S point, respectively. The estimated perforator flap area is 2.5 cm * 1.5
      cm and 4.5 cm * 2.5 cm for single and double perforators, respectively.
      CONCLUSIONS: MPAP flap was proved as another ideal option for finger pulp
      reconstruction. Its limitation is small size of perforators but this can be
      overcome by using MPA for microsurgical anastomosis instead.

PMID- 29575167
TI  - Empirical treatment of outpatients with gastroesophageal reflux disease with
      proton pump inhibitors: A survey of Chinese patients (the ENLIGHT Study).
AB  - BACKGROUND AND AIM: Empirical proton pump inhibitor (PPI) treatment is
      recommended as a diagnostic indicator for gastroesophageal reflux disease (GERD)
      and as a therapy for symptomatic control, with responses generally seen within 4
      weeks. However, there are no real-world data assessing the effectiveness of short
      term empirical treatment with PPIs in patients with GERD in China. METHODS: The
      ENLIGHT study was a multicenter, prospective, observational study conducted in
      China. The primary outcome was the overall response rate after 4 weeks' empirical
      treatment with PPIs. Adult patients aged between 18 and 65 years of age, with a
      gastroesophageal reflux disease questionnaire score of >= 8, prescribed empirical
      PPI treatment by their physicians and with no planned endoscopy were eligible to
      participate. Statistical analyses were primarily descriptive. RESULTS: Overall,
      987 patients were eligible to participate and were included in the full analysis
      set (FAS); 707 patients were included in the per protocol set. In the FAS,
      esomeprazole was received by 57.1% of patients and was the most commonly used
      PPI. After 4-week treatment, 71.1% (95% confidence interval [CI], 67.9% to 74.2%)
      of patients were considered responders to PPI. The response rate at the end of 2
      week PPI treatment reached 57.0% (95% CI, 52.5% to 61.7%). The median time to
      response was 13 days (95% CI, 12 to 15). Response rates at 2 and 4 weeks of the
      per protocol set were similar to those of the FAS. CONCLUSIONS: Short-term
      empirical PPI treatment can provide an effective relief of GERD symptoms in most
      Chinese patients in real-world practice.

PMID- 29575168
TI  - Site-level risk predictors of peri-implantitis: A retrospective analysis.
AB  - AIM: The goal of the present investigation was to identify site-level factors
      that might allow prognostication of individual implants in partially dentate
      patients with multiple non-splinted restorations. METHODS: We analysed clinical
      and radiographic characteristics of 222 non-splinted single implants in function
      for at least 5 years in 86 partially dentate individuals at the time of
      functional loading and at follow-up, with the outcome variable being peri
      implantitis. Principal component analysis identified factors contributing to
      greatest variability and linear discriminant analysis coupled with Random Forest
      Classifier used to identify risk predictors. RESULTS: After controlling for
      patient-level factors, the following characteristics were associated with
      significantly increased risk for peri-implantitis: Periodontal disease on
      adjoining teeth at the time of restoration (Odds Ratio (OR): 8.0), implant
      placement at a depth of 6 mm or more in relation to the CEJ of adjacent tooth
      (OR: 8.5), asymmetric prosthesis (OR: 4.3), history of tooth loss due to
      periodontitis (OR: 2.4) and a mean baseline plaque index of 1.6 or more (OR:
      7.9). CONCLUSIONS: Our findings suggest that a system that incorporates both
      subject level and implant-level factors is required to effectively prognosticate
      the success of individual implants.

PMID- 29575169
TI  - Laser capture microdissection for detecting the expression of epithelial
      mesenchymal transition-related genes in epithelial and spindle cells of paraffin
      embedded formalin-fixed biphasic synovial sarcoma.
AB  - Synovial sarcoma (SS) is a mesenchymal malignant neoplasm showing characteristics
      of epithelial-mesenchymal biphasic differentiation. SS is of uncertain cellular
      origin; however, studies have suggested that SS originates from a somatic stem
      cell population. In this study, we aim to determine whether differential
      morphological features of the epithelial-mesenchymal transition (EMT) contributed
      to the tumourigenesis of SS invasion and metastasis. Twelve paraffin-embedded
      formalin-fixed tissue (FFPE) SS tissue specimens were obtained, and laser capture
      microdissection (LCM) with the ArcturusXT system and small chip method (SCM) were
      used to isolate and purify spindle and epithelial cells from SS specimens. The
      TRIzol method was used to extract RNA, and the mRNA levels of EMT-related genes
      in epithelial and spindle cells of SS specimens were measured using real-time
      fluorescent quantitative reverse transcription polymerase chain reaction (qRT
      PCR). The results show that collection of about 2 * 104 cells from FFPE samples
      using LCM was sufficient for qRT-PCR, with an efficiency of 75%. Compared with
      LCM, 72.2% (13 of 18) RNA samples were successfully extracted using SCM to
      isolate cells from FFPE SS tissues. In the 16 samples (11 spindle cell samples
      and 5 epithelial cell samples), Snail mRNA was significantly upregulated in
      spindle cell areas compared with that in epithelial cell areas (P = .001).
      Expression levels of the epithelial marker E-cadherin and the mesenchymal marker
      N-cadherin were not significantly different between epithelial and spindle cell
      areas. In spindle cells of recurrent SS samples, the mRNA levels of E-cadherin, N
      cadherin, Snail, and Slug were higher in primary SS samples than in recurrent
      samples. Taken together, our results indicated that in SS samples, Snail mRNA was
      upregulated in spindle cell areas compared with that in epithelial cell areas and
      that the expression of EMT-related genes was increased in primary SS. LCM could
      be used to isolate and purify RNA from FFPE samples.

PMID- 29575170
TI  - Random-effects meta-analysis of the clinical utility of tests and prediction
      models.
AB  - The use of data from multiple studies or centers for the validation of a clinical
      test or a multivariable prediction model allows researchers to investigate the
      test's/model's performance in multiple settings and populations. Recently, meta
      analytic techniques have been proposed to summarize discrimination and
      calibration across study populations. Here, we rather consider performance in
      terms of net benefit, which is a measure of clinical utility that weighs the
      benefits of true positive classifications against the harms of false positives.
      We posit that it is important to examine clinical utility across multiple
      settings of interest. This requires a suitable meta-analysis method, and we
      propose a Bayesian trivariate random-effects meta-analysis of sensitivity,
      specificity, and prevalence. Across a range of chosen harm-to-benefit ratios,
      this provides a summary measure of net benefit, a prediction interval, and an
      estimate of the probability that the test/model is clinically useful in a new
      setting. In addition, the prediction interval and probability of usefulness can
      be calculated conditional on the known prevalence in a new setting. The proposed
      methods are illustrated by 2 case studies: one on the meta-analysis of published
      studies on ear thermometry to diagnose fever in children and one on the
      validation of a multivariable clinical risk prediction model for the diagnosis of
      ovarian cancer in a multicenter dataset. Crucially, in both case studies the
      clinical utility of the test/model was heterogeneous across settings, limiting
      its usefulness in practice. This emphasizes that heterogeneity in clinical
      utility should be assessed before a test/model is routinely implemented.

PMID- 29575172
TI  - Pharmacotherapy Rounds: Can We Improve the Fate of Unused Drugs?

PMID- 29575171
TI  - Nonlinear Optics with 2D Layered Materials.
AB  - 2D layered materials (2DLMs) are a subject of intense research for a wide variety
      of applications (e.g., electronics, photonics, and optoelectronics) due to their
      unique physical properties. Most recently, increasing research efforts on 2DLMs
      are projected toward the nonlinear optical properties of 2DLMs, which are not
      only fascinating from the fundamental science point of view but also intriguing
      for various potential applications. Here, the current state of the art in the
      field of nonlinear optics based on 2DLMs and their hybrid structures (e.g., mixed
      dimensional heterostructures, plasmonic structures, and silicon/fiber integrated
      structures) is reviewed. Several potential perspectives and possible future
      research directions of these promising nanomaterials for nonlinear optics are
      also presented.

PMID- 29575173
TI  - Vascular supply of the femoral head in sheep-Implications for the ovine
      femoroacetabular impingement model.
AB  - Sheep hips have a natural non-spherical head similar to a cam-type deformity in
      human beings. By performing an intertrochanteric varus osteotomy, cam-type
      femoroacetabular impingement can be induced experimentally. In sheep, the
      aspherical portion is located superiorly-exactly matching the region where the
      superior retinacular vessels enter the femoral head-neck junction in human
      beings. In order to fully exploit the potential of this experimental FAI model, a
      safe osteochondroplasty of the superior asphericity would need to be done without
      the risk of avascular necrosis. The aim of this study was to describe the
      vascular anatomy of the femoral head in sheep from the aorta to the retinacular
      vessels in order to perform safe femoral osteochondroplasty of the superior
      femoral asphericity in sheep. Sixty-two ovine hips were analyzed using CT
      angiography (30 hips), post mortem intravascular latex injection (6 hips),
      vascular corrosion casting (6 hips), and analysis of the distribution of vascular
      foramina around the femoral head-neck junction in macerated ovine femora (20
      hips). The ovine femoral head receives its blood supply from anterior retinacular
      arteries from the lateral femoral circumflex artery, and from posterior
      retinacular arteries from the medial femoral circumflex artery. The superior
      aspherical portion is free of vessels. Detailed knowledge about vascular anatomy
      of sheep hips is of clinical significance since it allows to perform
      osteochondroplasty of the superior aspherical portion in the experimental ovine
      FAI model safely without the risk of osteonecrosis. (c) 2018 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2340-2348, 2018.

PMID- 29575174
TI  - Sr[BeSi2 N4 ]:Eu2+ /Ce3+ and Eu[BeSi2 N4 ]: Nontypical Luminescence in Highly
      Condensed Nitridoberyllosilicates.
AB  - M[BeSi2 N4 ] (M=Sr,Eu), crystallizing in the hexagonal space group P6? 2c, was
      synthesized from Sr(NH2 )2 , Be3 N2 , and "Si(NH)2 " in W crucibles under a N2
      atmosphere in a radio-frequency furnace. The crystal structure was solved from
      powder X-ray diffraction data by the charge-flipping method (Sr[BeSi2 N4 ]:
      a=4.86082(2), c=9.42264(4) A, Z=2; Eu[BeSi2 N4 ]: a=4.85848(1), c=9.41615(4) A).
      M[BeSi2 N4 ] contains a highly condensed rigid network of trigonal planar [BeN3 ]
      units that are connected to Si2 N7 double tetrahedra by common vertices. M[BeSi2
      N4 ] (M=Sr,Eu) are the first examples of nitridoberyllosilicates and are isotypic
      to the oxoberyllate Sr[Be3 O4 ]. Eu2+ -doped Sr[BeSi2 N4 ] and Eu[BeSi2 N4 ] show
      orange-trapped exciton emission (lambdaem =605 nm, fwhm ~126 nm), whereas Ce3+ 
      doped samples of Sr[BeSi2 N4 ] show nontypical yellowish-orange luminescence.
      Sr[BeSi2 N4 ] has a large band gap of ~4.4 eV and shows high chemical and thermal
      stability. Eu2+ -doped beryllates with regular 4f6 5d1 ->4f7 -emission could be
      interesting for future application in LEDs upon doping with Eu2+ or Ce3+ due to
      large band gaps, rigid networks, and chemical and thermal stability.

PMID- 29575175
TI  - Cucurbitacin I induces pro-death autophagy in A549 cells via the ERK-mTOR-STAT3
      signaling pathway.
AB  - Natural products are a great source of cancer chemotherapeutic agents. In the
      present study, the anticancer effects of cucurbitacin I on A549 cells were
      investigated. Cucurbitacin I decreased cell viability, inhibited colony
      formation, and induced apoptosis in A549 cells. Cucurbitacin I caused
      accumulation of autophagosome and dose-dependent expression of LC3II protein.
      Autophagy inhibitors 3-methyladenine (3-MA) inhibited autophagy induced by
      cucurbitacin I and relieved cucurbitacin I-triggered cell death and apoptosis in
      A549 Cells. Cucurbitacin I treatment inhibits the ERK activation and the
      downstream phosphorylation level of mTOR and STAT3, but not the PI3K/Akt pathway.
      Furthermore, treatment with the mTOR activator MHY-1485, which also suppressed
      cucurbitacin I-induced LC3II expression, and also reversed cucurbitacin I-induced
      cell death and apoptosis. Taken together, these results suggest that cucurbitacin
      I induced pro-death autophagy through ERK/mTOR/STAT3 signaling cascade in A549
      cells.

PMID- 29575176
TI  - Rapid synthesis of maleimide functionalized fluorine-18 labeled prosthetic group
      using "radio-fluorination on the Sep-Pak" method.
AB  - Following our recently published fluorine-18 labeling method, "Radio-fluorination
      on the Sep-Pak", we have successfully synthesized 6-[18 F]fluoronicotinaldehyde
      by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium
      salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate
      (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO3 ). Over
      80% radiochemical conversion was observed using 10 mg of precursor within 1
      minute. The [18 F]fluoronicotinaldehyde ([18 F]5) was then conjugated with 1-(6
      (aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled
      maleimide functionalized prosthetic group, 6-[18 F]fluoronicotinaldehyde O-(6
      (2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[18 F]FPyMHO ([18 F]6). The
      current Sep-Pak method not only improves the overall radiochemical yield (50 +/-
      9%, decay-corrected, n = 9) but also significantly reduces the synthesis time
      (from 60-90 minutes to 30 minutes) when compared with literature methods for the
      synthesis of similar prosthetic groups.

PMID- 29575177
TI  - A longitudinal study of fractures in 1488 Thoroughbred racehorses receiving
      intrasynovial medication: 2006-2011.
AB  - BACKGROUND: There is a need for investigation of associations between
      intrasynovial medication and fracture risk in racehorses. OBJECTIVES: To document
      the proportion and type of fracture occurring following intrasynovial medication.
      STUDY DESIGN: Retrospective longitudinal study. METHODS: Review of clinical
      records from all Thoroughbred flat racehorses receiving intrasynovial medication
      under the care of a first-opinion veterinary practice between 2006 and 2011.
      Fractures pre- and post-medication were categorised by location, type, and
      severity; analysis of fractures sustained within 56-days of medication was
      undertaken. Survival analyses using Cox proportional hazards models were
      conducted for associations between medication used (corticosteroid vs. non
      corticosteroid), age at first medication, sex and total number of medications and
      fracture. RESULTS: A total of 1488 horses received intrasynovial medication
      during the period of study; 8692 synovial spaces were medicated in 3925 sessions.
      There were 96 fractures that occurred within 56-days of medication, of which 44
      were classified as 'serious' (44/1488; 3.0% total population, 95% CI 2.1, 3.8%)
      and 11 (11/1488, 0.7%, 95% CI 0.3, 1.2%) were euthanased due to severity of
      injury. Fifty-four of 96 cases (56.4%, 95% CI 46.3, 66.2%) returned to racing.
      Targeted imaging of the subsequent injury site was undertaken prior to injury in
      only 7 (7/96, 7.3%) horses that injured post-medication. Horses that had received
      >=3 previous intrasynovial medication sessions had an increased hazard of
      sustaining a fracture within 56 days (HR 2.31, 95% CI 1.51, 3.54, P<0.001)
      compared with those receiving <=3 medication sessions, adjusted for each
      increasing year of age (HR 0.67, 95% CI 0.53, 0.86, P = 0.001). MAIN LIMITATIONS:
      Absence of an unexposed cohort of nonmedicated racehorses. CONCLUSIONS: Serious
      musculoskeletal injury following intrasynovial medication occurred in 3%
      (44/1488) horses. Reduction in injury rates may be possible through greater use
      of premedication diagnostic imaging.

PMID- 29575179
TI  - Sensitization to minor cat allergen components is associated with type-2
      biomarkers in young asthmatics.
AB  - BACKGROUND: Cat allergy is a major trigger of asthma world-wide. Molecular
      patterns of cat sensitization vary between individuals, but their relationship to
      inflammation in asthmatics has not been extensively studied. OBJECTIVE: To
      investigate the prevalence and levels of IgE antibodies against different cat
      allergen components and their relationship to type-2 inflammation and total IgE
      among young asthmatic subjects sensitized to furry animals. METHODS: Patients
      with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse
      extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1
      (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins).
      Independent associations between IgE-antibody concentrations, and fraction of
      exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were
      analysed by multiple linear regression after adjustment for possible confounders.
      RESULTS: The level of IgE against Fel d 2 was independently related to FeNO (P =
      .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Beta-Eos
      count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat
      extract did not independently relate to these inflammatory markers (P = .23-.51).
      CONCLUSIONS: Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2),
      but not to secretoglobin (Fel d 1) or cat extract, were independently associated
      with type-2 biomarkers and total IgE in young asthmatics. CLINICAL RELEVANCE: We
      suggest that measurement of IgE to minor cat allergen components may be useful
      when investigating asthma morbidity in cat allergic subjects.

PMID- 29575180
TI  - Sonographic assessment of the anal sphincter after obstetric anal sphincter
      injury (OASI) using transperineal ultrasound (TPUS).
AB  - Obstetric anal sphincter injury (OASI) is the most common cause of anal
      incontinence and ano-rectal symptoms in women1 . Reported rates of anal
      incontinence following primary repair of OASI range between 15-61%, with a mean
      of 39%2, 3 . Other possible complications of OASI include perineal pain,
      dyspareunia, and less commonly, abscess formation, wound breakdown, and
      rectovaginal fistulae. Symptom onset may occur immediately, several years
      postpartum, or only late in life when aging of tissues adds to the delivery
      insult. Having sustained an OASI may impact significantly on women's physical and
      emotional health. Missed OASI, inadequate repair or lack of follow up are
      potential sources of litigation4 . The reported incidence of OASI may be as high
      as 4-6.6%4 , averaging 2.9% in the UK3 . The incidence is higher in primiparae
      (6.1%) than in multiparae (1.7%) 3 . Recent years are seeing an increased
      awareness and structured training programs, which appear to have resulted in an
      increase in the detection rate of OASI3 . The following risk factors have been
      identified with varying risk rates reported3 : Asian ethnicity (OR 2.27, 95% CI
      2.14-2.41), nulliparity (relative risk [RR] 6.97, 95% CI 5.40-8.99), birth weight
      greater than 4 kg (OR 2.27, 95% CI 2.18-2.36), shoulder dystocia (OR 1.90, 95% CI
      1.72-2.08), occipito-posterior position (RR 2.44, 95% CI 2.07-2.89), prolonged
      second stage of labor (up to RR 2.02, 95% CI 1.62-2.51 after four hours
      duration). Instrumental deliveries and episiotomy use have been extensively
      studied resulting in the following evidence: Vacuum delivery without episiotomy
      (OR 1.89, 95% CI 1.74-2.05); vacuum delivery with episiotomy is protective (OR
      0.57, 95% CI 0.51-0.63); forceps delivery without episiotomy carries the highest
      potential risk (OR 6.53, 95% CI 5.57-7.64); and forceps delivery with episiotomy
      (OR 1.34, 95% CI 1.21-1.49). Other potential risk factors have been suggested
      with varying evidence such as advanced maternal age at first birth, Asian race, a
      vaginal birth after cesarean, and type of obstetrical care provider4 . Possible
      protective factors include obesity, perineal massage (RR 0.91, 95% CI 0.86-0.96)5
      , perineal protection at crowning3 , warm compression during the second stage of
      labor (RR 0.48, 95% CI 0.28-0.84)3 , mediolateral episiotomy in instrumental
      deliveries6 , a wide angle of the mediolateral episiotomy (at least 60 degrees
      away from the midline when the perineum is distended) 7 , and pre-labor cesarean
      section4 . However, clinicians and patients alike should be aware that risk
      factors do not allow the accurate prediction of OASI3 . OASI is usually diagnosed
      in the immediate postpartum period. The classification is based on the extent of
      lacerations to the external and internal anal sphincter (EAS and IAS,
      respectively) and epithelium as devised by Sultan 2,3,8 (Figure 1) and adopted by
      the World Health Organization (WHO). The degree of damage impacts on the
      development of symptoms, with 3C and 4th degree tears carrying a graver prognosis
      than 3A and 3B tears9 . It is not unusual for a tear to be missed in the labor
      ward: the reported rates of missed OASI range from 26-87%10 . Since all women
      having a vaginal delivery are at risk of sustaining OASI, they should be examined
      systematically, including a digital rectal examination, to assess the severity of
      damage, prior to suturing3 .

PMID- 29575178
TI  - Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR
      molecular imaging of human prostate cancer.
AB  - PURPOSE: The purpose of this study was to develop a new 3D dynamic carbon-13
      compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test
      it in phantoms, animal models, and then in prostate cancer patients to image the
      metabolic conversion of hyperpolarized [1-13 C]pyruvate to [1-13 C]lactate with
      whole gland coverage at high spatial and temporal resolution. METHODS: A 3D
      dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation
      was designed to meet the required spatial coverage, time and spatial resolution,
      and RF limitations of the 3T MR scanner for its clinical translation for prostate
      cancer patient imaging. After phantom testing, animal studies were performed in
      rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab
      polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized
      sterile GMP [1-13 C]pyruvate. 3D dynamic 13 C CS-EPSI data were acquired starting
      5 s after injection throughout the gland with a spatial resolution of 0.5 cm3 ,
      18 time frames, 2-s temporal resolution, and 36 s total acquisition time.
      RESULTS: Through preclinical testing, the 3D CS-EPSI sequence developed in this
      project was shown to provide the desired spectral, temporal, and spatial 5D HP 13
      C MR data. In human studies, the 3D dynamic HP CS-EPSI approach provided first
      ever simultaneously volumetric and dynamic images of the LDH-catalyzed conversion
      of [1-13 C]pyruvate to [1-13 C]lactate in a biopsy-proven prostate cancer patient
      with full gland coverage. CONCLUSION: The results demonstrate the feasibility to
      characterize prostate cancer metabolism in animals, and now patients using this
      new 3D dynamic HP MR technique to measure kPL , the kinetic rate constant of [1
      13 C]pyruvate to [1-13 C]lactate conversion.

PMID- 29575181
TI  - Familial papular epidermal nevus with "skyline" basal cell layer.
AB  - Papular epidermal nevus with "skyline" basal cell layer is a variant of
      keratinocytic nevus that usually occurs sporadically but may affect different
      family members. We report on the fourth family with papular epidermal nevus with
      "skyline" basal cell layer affecting a 3-month-old girl and her father.

PMID- 29575182
TI  - Comparison of pre- and post-transplant sun-safe behavior of kidney transplant
      recipients: What is needed to improve?
AB  - BACKGROUND: The role of sun exposure in the development of melanoma and
      nonmelanoma skin cancers is known; however, there are limited data on the
      contribution of pretransplantation total sun burden (TSB) to the increased skin
      cancer risk in organ transplant recipients (OTRs). The importance of patient
      education about sun-safe behaviors is understood, but educations are often
      unsuccessful in OTRs. METHODS: A questionnaire-based cross-sectional study was
      performed with kidney transplant patients at a single academic center to assess
      the pre- and post-transplant sun exposure, sun protection habits, and skin
      cancers. RESULTS: Two hundred and twenty-one patients participated in the study.
      13.1% developed at least one skin cancer. High total sun burden before
      transplantation was reported by 58.4%, and 65.2% reported education about
      increased skin cancer risk at the time of transplantation. However, that
      education did not lead to less sun exposure or better sun protection methods
      after transplantation. Overall, OTR related but not sun protection-guided
      lifestyle changes affecting OTRs after transplantation led to reduction in sun
      exposure. CONCLUSION: Our findings highlight the need for more tailored,
      population-specific education programmes, even for patients who expect to receive
      a transplant in the future, and suggest the importance of pretransplantation TSB
      in determining the post-transplant skin cancer risk.

PMID- 29575183
TI  - Giant cell tumour of tendon sheath: A 10-year study from a tertiary care centre.
AB  - INTRODUCTION: Cytology of giant cell tumour of tendon sheath (GCTTS) is often
      sufficient to diagnose this lesion and has been previously described in small
      series. The present study was undertaken to evaluate detailed cytomorphological
      features and differential diagnostic entities and pitfalls in the diagnosis.
      METHODS: All the cases of GCTTS reported on FNAC were retrieved from July 2007 to
      June 2017. The cases were reviewed for various cytomorphological features, which
      were correlated with follow-up histopathology wherever available. RESULTS: A
      total of 72 cases of GCTTS were retrieved, follow-up histopathology was available
      in 20 cases. The common sites of involvement were fingers and palm followed by
      wrists, elbow, knee, ankle and shoulder. The characteristic cytomorphology
      consisted of mononuclear cells, multinucleated giant cells and pigment laden
      macrophages in variable numbers. There were four discordant cases that were
      confirmed on histopathology as sarcoidosis, melanoma, fibrous histiocytoma and
      eumycetoma. CONCLUSIONS: GCTTS can be confused cytologically with giant cell rich
      lesions of bone and soft tissue and pigment containing lesions including
      melanoma. Ladybird cell is a characteristic feature seen in this lesion. Proper
      clinicoradiological correlation is essential before offering a diagnosis of GCTTS
      on cytology.

PMID- 29575184
TI  - A Multifaceted Study of Methane Adsorption in Metal-Organic Frameworks by Using
      Three Complementary Techniques.
AB  - Methane is a promising clean and inexpensive energy alternative to traditional
      fossil fuels, however, its low volumetric energy density at ambient conditions
      has made devising viable, efficient methane storage systems very challenging.
      Metal-organic frameworks (MOFs) are promising candidates for methane storage. In
      order to improve the methane storage capacity of MOFs, a better understanding of
      the methane adsorption, mobility, and host-guest interactions within MOFs must be
      realized. In this study, methane adsorption within alpha-Mg3 (HCO2 )6 , alpha-Zn3
      (HCO2 )6 , SIFSIX-3-Zn, and M-MOF-74 (M=Mg, Zn, Ni, Co) has been comprehensively
      examined. Single-crystal X-ray diffraction (SCXRD) experiments and DFT
      calculations of the methane adsorption locations were performed for alpha-Mg3
      (HCO2 )6 , alpha-Zn3 (HCO2 )6 , and SIFSIX-3-Zn. The SCXRD thermal ellipsoids
      indicate that methane possesses significant mobility at the adsorption sites in
      each system. 2 H solid-state NMR (SSNMR) experiments targeting deuterated CH3 D
      guests in alpha-Mg3 (HCO2 )6 , alpha-Zn3 (HCO2 )6 , SIFSIX-3-Zn, and MOF-74 yield
      an interesting finding: the 2 H SSNMR spectra of methane adsorbed in these MOFs
      are significantly influenced by the chemical shielding anisotropy in addition to
      the quadrupolar interaction. The chemical shielding anisotropy contribution is
      likely due mainly to the nuclear independent chemical shift effect on the MOF
      surfaces. In addition, the 2 H SSNMR results and DFT calculations strongly
      indicate that the methane adsorption strength is linked to the MOF pore size and
      that dispersive forces are responsible for the methane adsorption in these
      systems. This work lays a very promising foundation for future studies of methane
      adsorption locations and dynamics within adsorbent MOF materials.

PMID- 29575185
TI  - Identification of VIM-2 metallo-beta-lactamase-producing Pseudomonas aeruginosa
      isolated from dogs with pyoderma and otitis in Korea.
AB  - BACKGROUND: Pseudomonas aeruginosa is a challenging pathogen cultured from cases
      of acute and chronic canine otitis and sometimes in cases of deep pyoderma. The
      spread of antimicrobial resistance, especially carbapenem resistance, is a
      serious therapeutic challenge worldwide. HYPOTHESIS/OBJECTIVES: To investigate
      the identification and characterization of resistant P. aeruginosa clinical
      canine isolates. MATERIALS: Clinical isolates (n = 80) were collected from dogs
      with pyoderma (n = 18) and otitis (n = 62) in Korea. METHODS: Antimicrobial
      susceptibility was determined using agar dilution and using Clinical and
      Laboratory Standards Institute guidelines for recording susceptibility for human
      Pseudomonas isolates; genetic relatedness of isolates was investigated by
      multilocus sequence typing (MLST) and SpeI macrorestriction analysis. The class 1
      integrons were amplified and sequenced using primer walking. RESULTS: Most
      isolates were susceptible to colistin (97.5%), polymyxin B (96.3%), ciprofloxacin
      (81.3%) and meropenem (80.0%); whereas resistance to aztreonam (80%),
      piperacillin (52.5%), piperacillin/tazobactam (41.3%) and cefepime (37.5%) was
      high; 12 carbapenem-nonsusceptible isolates (15%) were detected. MLST revealed 45
      different sequence types (STs) and macrorestriction analysis detected 55 distinct
      pulsotypes (PTs), which were divided into 25 clonal groups. Among carbapenem
      nonsusceptible isolates, 10 (83.3%) were VIM-2-producing strains. Nine VIM-2
      producing isolates were identified as ST1047 and harboured the same 2.8 kb class
      1 integron. One remaining isolate was ST1203 with 2.1 kb class 1 integron.
      CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated the diversity of the
      phenotype and genotype of clinical P. aeruginosa isolates from dogs with pyoderma
      and otitis. The identification of VIM-2-producing P. aeruginosa in dogs is
      alarming and warrants further surveillance.

PMID- 29575187
TI  - Culex pipiens sperm motility is initiated by a trypsin-like protease from male
      accessory glands.
AB  - In most animals, sperm are stored in a quiescent state in the male reproductive
      tract and only initiate motility when released into either the female
      reproductive tract, or, in the case of broadcast spawners, the external
      environment. Male accessory gland secretions transferred into the female
      reproductive tract may provide factors that modulate sperm viability and storage,
      or aid in sperm competition, as well as activate sperm motility. In several
      insects, serine proteases have been implicated in activating sperm motility. Our
      previous studies have shown that, in Culex quinquefasciatus, either a male
      accessory gland extract or purified trypsin is sufficient to initiate sperm
      motility in vitro. The objective of this study was to identify and characterize
      trypsin-like enzymes produced in the Culex male accessory glands. Mass
      spectrometry was used to analyze accessory gland proteins and this preliminary
      proteomic analysis identified 4 trypsin-like proteases (trypsin, trypsin4, and
      two trypsin7 isoforms). When measured with the chromogenic trypsin substrate Na 
      benzoyl-L-arginine-ethyl-ester-hydrochloride (BAEE), trypsin-like protease
      activity in the accessory glands was robust, with a pH optimum of 8. The pH range
      for the Culex trypsin activity was substantially narrower than a mammalian
      homologue (porcine pancreatic trypsin). A soybean trypsin inhibitor (SBTI) 
      agarose affinity column was used to independently identify trypsin-like accessory
      gland proteins. Several proteins were enriched in the eluate, as detected by
      silver staining of SDS-PAGE gels. Taken together, these data demonstrate the
      presence of trypsin-like activity and several trypsin-like proteins in the Culex
      male accessory glands.

PMID- 29575186
TI  - Nitrogen-Functionalized Hydrothermal Carbon Materials by Using Urotropine as the
      Nitrogen Precursor.
AB  - Nitrogen-containing hydrothermal carbon (N-HTC) materials of spherical particle
      morphology were prepared by means of hydrothermal synthesis with glucose and
      urotropine as precursors. The molar ratio of glucose to urotropine has been
      varied to achieve a continuous increase in nitrogen content. By raising the ratio
      of urotropine to glucose, a maximal nitrogen fraction of about 19 wt % could be
      obtained. Decomposition products of both glucose and urotropine react with each
      other; this opens up a variety of possible reaction pathways. The pH has a
      pronounced effect on the reaction pathway of the corresponding reaction steps.
      For the first time, a comprehensive analytical investigation, comprising a
      multitude of analytical tools and instruments, of a series of nitrogen-containing
      HTC materials was applied. Functional groups and structural motifs identified
      were analyzed by means of FTIR spectroscopy, thermogravimetric MS, and solid
      state NMR spectroscopy. Information on reaction mechanisms and structural details
      were obtained by electronic structure calculations that were compared with
      vibrational spectra of polyfuran or polypyrrole-like groups, which represent
      structural motifs occurring in the present samples.

PMID- 29575188
TI  - Hand fasciae innervation: The palmar aponeurosis.
AB  - There are few data in the scientific literature about the innervation of fasciae
      of the hand. The present study first elucidates the density and location of
      nervous structures in the palmar aponeurosis and, for comparison, in the flexor
      retinaculum (both can be considered specializations of the deep fascia of the
      upper limbs). Second, it compares nonpathological with pathological palmar
      aponeurosis. Samples of nonpathological fascia were taken from the flexor
      retinaculum and palmar aponeurosis of 16 upper limbs of unembalmed cadavers.
      Samples of pathological palmar aponeurosis were taken from seven patients with
      Dupuytren's disease. All samples were stained immunohistochemically with anti
      S100 and anti-tubulin antibodies, and analyzed quantitatively and qualitatively
      by microscopy. The palmar aponeurosis showed higher median density than the
      retinacula of free nerve endings (22 and 20 elements/cm2 , respectively),
      Pacinian corpuscles (2 and 0 elements/cm2 ) and Golgi-Mazzoni corpuscles (1.0 and
      0.5 element/cm2 ). Some corpuscles were located at the intersections of the
      fibers in the three directions. Free nerve endings were denser in pathological
      palmar aponeurosis (38 elements/cm2 ). The results indicate that the palmar
      aponeurosis is central to proprioception of the hand and that surgery should
      therefore avoid injuring it. The higher density of free nerve endings in
      pathological samples indicates that the nervous structures are implicated in the
      amplified fibrosis of Dupuytren's disease. Clin. Anat. 31:677-683, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29575189
TI  - Appraisal of systematic reviews on the management of peri-implant diseases with
      two methodological tools.
AB  - AIM: This study aimed to evaluate and compare the performance of two
      methodological instruments to appraise systematic reviews and to identify
      potential disagreements of systematic review authors regarding risk of bias (RoB)
      evaluation of randomized controlled trials (RCTs) included in systematic reviews
      on peri-implant diseases. MATERIAL/METHODS: We searched Medline, Web of Science,
      Cochrane Library, PubMed Central, and Google Scholar for systematic reviews on
      peri-implant diseases published before July 11, 2017. Two authors independently
      evaluated the RoB and methodological quality of the systematic reviews by
      applying the Risk of Bias in Systematic Reviews (ROBIS) tool and Assessing the
      Methodological Quality of Systematic Reviews (AMSTAR) checklist, respectively. We
      assessed the RoB scores of the same RCTs published in different systematic
      reviews. RESULTS: Of the 32 systematic reviews identified, 23 reviews addressed
      the clinical topic of peri-implantitis. A high RoB was detected for most
      systematic reviews (n=25) using ROBIS, whilst five systematic reviews displayed
      low methodological quality by AMSTAR. Almost 30% of the RoB comparisons (for the
      same RCTs) had different RoB ratings across systematic reviews. CONCLUSIONS: The
      ROBIS tool appears to provide more conservative results than AMSTAR checklist.
      Considerable disagreement was found among systematic review authors rating the
      same RCT included in different systematic reviews.

PMID- 29575190
TI  - Photocatalysis with Quantum Dots and Visible Light for Effective Organic
      Synthesis.
AB  - Colloidal semiconductor quantum dots (QDs) have recently attracted widespread
      interest for diverse applications. Owing to their quantum confinement effects,
      rich surface binding properties, high surface-to-volume ratios, broad and intense
      absorption spectra in the visible region, and low cost as well, QDs offer new and
      versatile ways to serve as photocatalysts for organic synthesis. Most recently,
      the use of QDs photocatalysts is springing up in organic synthesis. Herein, we
      highlight the recent advances of QDs used for smart and clean organic
      transformations.

PMID- 29575191
TI  - Synergistic anti-oomycete effect of melatonin with a biofungicide against
      oomycetic black shank disease.
AB  - Human health, food safety, and agriculture have been threatened by oomycetic
      diseases caused by notorious pathogenic oomycetes. Chemical oomyceticides are the
      main approaches in control of pathogenic oomycetes. However, the overused
      chemical oomyceticides have resulted in serious environmental pollution and drug
      resistance. The eco-friendly bio-oomyceticides are required for sustainable
      development through screening synergistic drug combinations. In this study,
      Phytophthora nicotianae (P. nicotianae), as one of the most destructive oomycetic
      diseases in agriculture, was used as a model system to screen the novel bio
      oomyceticides based on drug combination. The results showed that treatment of
      melatonin or ethylicin (IUPAC Name: 1-ethylsulfonylsulfanylethane) alone
      displayed similar phenotypes such as the inhibition of the hyphal growth,
      reduction of the cell viability, and suppression of the virulence of P.
      nicotianae. Importantly, melatonin and ethylicin shared the same targets of
      interfering with the amino acid metabolism, overexpressing apoptosis-inducing
      factor, and dysregulating the virulence-related genes. Furthermore, strong
      synergism against P. nicotianae was induced by combining melatonin with
      ethylicin. Under treatment of the combination of melatonin and ethylicin, the
      expression of genes associated with amino acid, the apoptosis-inducing factor,
      and the virulence-related genes was much more significantly dysregulated than
      that of single drug treatment. Thus, the tobacco black shank caused by P.
      nicotianae can be successfully controlled using the combination of melatonin and
      ethylicin. These observations suggest that the synergistic effect based on the
      combination of melatonin and ethylicin is an eco-friendly alternative for the
      control of the destructive oomycetic diseases.

PMID- 29575194
TI  - Hidradenitis suppurativa in children: The Henry Ford experience.
AB  - BACKGROUND: Although recent hidradenitis suppurativa studies have shown that
      early-onset disease is associated with a positive family history and more
      widespread disease, research in pediatric hidradenitis suppurativa is limited.
      METHODS: Thirty-three children diagnosed with hidradenitis suppurativa during an
      18-month period were included in this institutional review board-approved,
      retrospective chart review. Information on demographic characteristic, family
      history, and timing of onset (prepubescent vs postpubescent) was extracted. The
      Fisher exact test, Cochran-Armitage exact trend test, and chi-square test were
      used to examine the association between prepubescent or postpubescent onset of
      hidradenitis suppurativa and sex, disease severity, and family history. RESULTS:
      A significantly higher percentage of patients with postpubescent onset were
      female (85.7%) than male (14.3%), whereas those with prepubescent onset were more
      likely to be male (58.3%) than female (41.7%; P = .02). Associations between
      disease onset and positive family history of hidradenitis suppurativa (P = .47)
      or higher Hurley stage of disease (P = .15) were not statistically significant.
      CONCLUSION: Boys are more likely to have prepubescent onset of hidradenitis
      suppurativa and girls to have postpubescent onset. This shift in sex distribution
      is unexplained, but we hypothesize that, whereas the role of ovarian hormones in
      the pathogenesis of HS may underlie much of adult-onset disease, it is less
      important in prepubescent disease.

PMID- 29575193
TI  - Synaptic organization of the dorsal lateral geniculate nucleus.
AB  - A half century after Ray Guillery's classic descriptions of cell types, axon
      types, and synaptic architecture of the dorsal lateral geniculate nucleus, the
      functional organization of this nucleus, as well as all other thalamic nuclei, is
      still of enormous interest. This review will focus on two classic papers written
      by Ray Guillery: 'A study of Golgi preparations from the dorsal lateral
      geniculate nucleus of the adult cat', and 'The organization of synaptic
      interconnections in the laminae of the dorsal lateral geniculate nucleus of the
      cat', as well as the studies that most directly followed from the insights these
      landmark manuscripts provided. It is hoped that this review will honor Ray
      Guillery by encouraging further investigations of the synaptic organization of
      the dorsal thalamus.

PMID- 29575195
TI  - Ethnopharmacology, phytochemistry, and biotechnological advances of family
      Apocynaceae: A review.
AB  - The family Apocynaceae is one of the largest and important families in
      angiosperm. Several members of this family have medicinal properties and have
      been in the treatment of various ailments. Most of them are consumed as food by
      tribal people whereas a few plants are used as source of poison. Members of
      family Apocynaceae are rich in alkaloids, terpenoids, steroids, flavonoids,
      glycosides, simple phenols, lactones, and hydrocarbons. Other compounds such as
      sterols, lignans, sugars, lignans, and lactones have been isolated and
      systematically studied. Few studies have reported antioxidant, anti-inflammatory,
      antimicrobial, and cytotoxic activities of crude extracts as well as single
      compound(s) isolated from various members of the family Apocynaceae. Holarrhena
      antidysenterica, Rauvolfia serpentina, Carissa carandas, and Tabernaemontana
      divaricata are the extensively studied plants in this family. The present review
      provides a detailed outlook on ethnopharmacology, phytochemistry, and biological
      activities of selected members of this family. Moreover, it also covers the
      biotechnological advances used for large-scale production of bioactive compounds
      of therapeutic interest along with plant tissue culture-based approaches for
      conservation of this medicinally valuable family.

PMID- 29575196
TI  - Granulocyte and monocyte CD11b expression during plasma separation is dependent
      on complement factor 5 (C5) - an ex vivo study with blood from a C5-deficient
      individual.
AB  - The aim of the study was to investigate the role of complement factor 5 (C5) in
      reactions elicited by plasma separation using blood from a C5-deficient (C5D)
      individual, comparing it to C5-deficient blood reconstituted with C5 (C5DR) and
      blood from healthy donors. Blood was circulated through an ex vivo plasma
      separation model. Leukocyte CD11b expression and leukocyte-platelet conjugates
      were measured by flow cytometry during a 30-min period. Other markers were
      assessed during a 240-min period. Granulocyte and monocyte CD11b expression did
      not increase in C5D blood during plasma separation. In C5DR samples granulocytes
      CD11b expression, measured by mean fluorescence intensity (MFI), increased from
      10481 +/- 6022 (SD) to 62703 +/- 4936, and monocytes CD11b expression changed
      from 13837 +/- 7047 to 40063 +/- 713. Granulocyte-platelet conjugates showed a
      2.5-fold increase in the C5DR sample compared to the C5D sample. Monocyte
      platelet conjugates increased independently of C5. In the C5D samples, platelet
      count decreased from 210 * 109 /L (201-219) (median and range) to 51 * 109 /L (50
      51), and C3bc increased from 14 CAU/mL (21-7) to 198 CAU/mL (127-269), whereas
      TCC formation was blocked during plasma separation. In conclusion, up-regulation
      of granulocyte and monocyte CD11b during plasma separation was C5-dependent. The
      results also indicate C5 dependency in granulocyte-platelet conjugates formation.

PMID- 29575198
TI  - Down-regulation of microRNA-19b in hormone receptor-positive/HER2-negative breast
      cancer.
AB  - miR-19b (miR-19b-3p) has been reported to be correlated with either favorable or
      unfavorable events in several cancers. However, no study has been conducted to
      evaluate the expression level of miR-19b in patients with breast cancer (BC).
      This study was aimed to investigate the expression level of miR-19b in human
      malignant and healthy breast tissues with histopathology of ER+/PR+/HER2-. We
      performed a miRNA real-time PCR to detect differential expression of miR-19b in
      40 BC, including 17 BC with familial background and 23 BC without familial
      background, and 12 non-tumoral tissues. Moreover, a bioinformatics prediction
      upon miR-19b functionality in BC cells was performed. The miR-19b expression
      level was significantly down-regulated in BC, BC with familial background, and BC
      without familial background compared with its expression in normal tissue (p
      value, <0.0001; fold change, -7.45; p value, 0.0003; fold change, -6.45; and p
      value, 0.0005; fold change, -8.41, respectively). Moreover, according to the AUCs
      (area under curve) of receiver operating characteristic (ROC) curves, miR-19b can
      significantly distinguish all defined categories. Last, in agreement with our
      experimental findings, proteoglycans in cancer, pathways in cancer, FoxO
      signaling pathway, central carbon metabolism in cancer, p53 signaling pathway,
      transcriptional misregulation in cancer, and prolactin signaling pathway were
      predicted as miR-19b-related signaling pathways. In summary, down-regulation of
      miR-19b in BC vs healthy tissue suggests that mir-19b can function as a tumor
      suppressor. Our results shed additional information on controversial expression
      pattern of miR-19b depending on different cancer types.

PMID- 29575197
TI  - PTTG-1 (Securin) immunoexpression in meningiomas correlates with tumor grade and
      proliferation rate: potential use as a diagnostic marker of malignancy.
AB  - This study essentially aims to contribute to the immunohistochemical
      investigation of the use of pituitary tumor transforming gene (PTTG) as a marker
      of cell proliferation or advanced tumor grade in meningiomas of various WHO
      grades. In all, 51 cases were recovered in total, 21 Grade-I, 23 Grade-II and 7
      Grade-III meningiomas. Mitotic index (MI), Ki-67/MiB-1 positivity percentage and
      PTTG expression were analyzed in correlation to each other as well as to the
      tumor WHO grades. All three biomarkers showed a high diagnostic significance and
      a strong association with WHO grades. In comparison, PTTG expression was on a par
      with the other two indices, and performed very well regarding identification of
      advanced grade tumors. PTTG may be considered an important diagnostic tool and
      serve in the future as a novel prognosticator of the biological behavior of all
      grade meningiomas as well as a useful high-risk patient selection tool.

PMID- 29575199
TI  - Effect of matrix metalloproteinase-21 (572C/T) polymorphism on HIV-associated
      neurocognitive disorder.
AB  - Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a
      presumed reason for the development of HIV-associated neurocognitive disorders
      (HAND). The coding region polymorphism in MMP-21 572C/T gene may have a potential
      functional effect on ECM remodeling. Hence, we aimed to examine the association
      of MMP-21 polymorphism with the modulation of HAND severity and its prevalence in
      HIV-infected and healthy individuals. Genotyping of MMP-21 572C/T polymorphism
      was performed by PCR-RFLP in total 150 HIV-infected individuals, 50 with HAND,
      100 without HAND and 150 healthy controls. MMP-21 572TT genotype was
      predominantly higher in HAND patients compared with no HAND (OR = 1.63, p =
      0.57). MMP-21 572T allele was associated with reduce risk for HAND severity (OR =
      0.50, p = 0.04). Similarly, MMP-21 572TT genotype underrepresented in HIV
      infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p =
      0.08). MMP-21 572CT genotype and early HIV disease stage showed a higher risk for
      the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07).
      MMP-21 572CT genotype increased the risk for the modulation of HAND severity in
      tobacco users (OR = 1.98, p = 0.43). MMP-21 572CT genotype among tobacco and
      alcohol users showed elevated risk for the development of HAND in HIV-infected
      individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP-21 572TT
      genotype enhanced the risk for the development of HAND in tobacco users (OR =
      3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may
      have protection for HAND severity. MMP-21 572C/T polymorphism and tobacco and
      alcohol usage may facilitate the development of HAND.

PMID- 29575200
TI  - Oxidative stress in normal hematopoietic stem cells and leukemia.
AB  - Leukemia is developed following the abnormal proliferation of immature
      hematopoietic cells in the blood when hematopoietic stem cells lose the ability
      to turn into mature cells at different stages of maturation and differentiation.
      Leukemia initiating cells are specifically dependent upon the suppression of
      oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to
      start their activities. Relevant literature was identified by a PubMed search
      (2000-2017) of English-language literature using the terms 'oxidative stress,'
      'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The
      generation and degradation of free radicals is a main component of the metabolism
      in aerobic organisms. A certain level of ROS is required for proper cellular
      function, but values outside this range will result in oxidative stress (OS).
      Long-term overactivity of reactive oxygen species (ROS) has harmful effects on
      the function of cells and their vital macromolecules, including the
      transformation of proteins into autoantigens and increased degradation of
      protein/DNA, which eventually leads to the change in pathways involved in the
      development of cancer and several other disorders. According to the metabolic
      disorders of cancer, the relationship between OS changes, the viability of cancer
      cells, and their response to chemotherapeutic agents affecting this pathway are
      undeniable. Recently, studies have been conducted to determine the effect of
      herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By
      emphasizing the role of oxidative stress on stem cells in the incidence of
      leukemia, this paper attempts to state and summarize this subject.

PMID- 29575201
TI  - Sebaceous carcinoma of the breast in a patient with a pathogenic BRCA2 (886delGT)
      mutation - focus on histopathologic and immunohistochemical features.
AB  - Sebaceous carcinoma of the breast (SCB) is a rare variant of ductal carcinoma
      arising within the mammary gland and containing at least 50% of malignant cells
      with sebaceous differentiation. Only 11 cases that adjust to the criteria
      delineated in the WHO classification have been published in the English
      literature, to the best of our knowledge. Here, we present the first SCB arising
      in the context of a deleterious BRCA2 mutation, focusing on the histopathologic
      and immunohistochemical features of this exceedingly rare tumor.

PMID- 29575202
TI  - Sliding sign in third-trimester sonographic evaluation of intra-abdominal
      adhesions in women undergoing repeat Cesarean section: a novel technique.
AB  - OBJECTIVE: Intra-abdominal adhesions are associated with an increased risk of
      complications during repeat Cesarean section (CS), such as bladder and bowel
      injury, hemorrhage, infection and hysterectomy. We present a simple sonographic
      marker, the 'sliding sign' of the uterus, for the prediction of intra-abdominal
      adhesions in the third trimester of pregnancy in women undergoing repeat CS.
      METHODS: This was a prospective observational study of pregnant women with a
      history of at least one Cesarean delivery evaluated by transabdominal ultrasound
      during the third trimester of an ongoing pregnancy. In order to diagnose intra
      abdominal adhesions, we assessed a sonographic sign, the sliding of the uterus
      under the inner part of the fascia of the abdominal muscles during deep
      breathing. Women were considered to be at high risk for severe adhesions if
      uterine sliding was absent and at low risk in the presence of obvious or moderate
      uterine sliding. A comparison between sonographic findings and intra-abdominal
      adhesions observed during surgery was performed. RESULTS: Of the 63 patients with
      one or more previous CS examined, 59 completed the study and underwent CS at our
      institution. In 16 of the 19 cases assigned to the high-risk group for severe
      adhesions due to absence of sliding of the uterus, the suspicion was confirmed at
      surgery. The prediction of low risk for adhesions was confirmed in 35 out of 40
      patients. The sensitivity and specificity of the sliding sign in predicting
      presence of intra-abdominal adhesions in women undergoing repeat CS were 76.2%
      and 92.1%, respectively. Inter- and intraobserver correlation using Cohen's kappa
      coefficient were 0.52 and 0.77, respectively. CONCLUSION: Our data show that a
      simple sonographic sign might be able to discriminate between high and low risk
      for intra-abdominal adhesions in patients with a history of Cesarean delivery.
      This technique may aid clinical decisions in patients undergoing repeat CS.
      Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29575203
TI  - Glucocorticoids inhibit notch target gene expression in osteoblasts.
AB  - Glucocorticoids in excess suppress osteoblast function and cause osteoporosis. We
      demonstrated that cortisol induces the expression of selected Notch receptors in
      osteoblasts, revealing a potential mechanism for the skeletal effects of
      glucocorticoids. However, it remains to be determined whether increased
      expression of Notch receptors results into enhanced signaling. Following
      activation of Notch, its intracellular domain (NICD) binds to the DNA-associated
      protein recombination signal binding protein for immunoglobulin kappa-J region
      (RBPJ) and induces the expression of target genes such as Hey1, Hey2, and HeyL.
      To determine whether glucocorticoids modulate Notch signaling in the skeleton, 1
      month old wild-type mice were administered prednisolone or placebo and sacrificed
      after 72 h, and gene expression was analyzed in femoral bone. Prednisolone
      induced Tsc22d3, a glucocorticoid target gene, and suppressed Hey1 and HeyL
      expression, which is indicative of inhibited Notch receptor activity or direct
      Hey downregulation. To determine the mechanisms of Hey suppression, wild-type
      osteoblast-enriched cells were seeded on the Notch cognate ligand Delta-like
      (DLL)1 or transfected with constructs expressing the NOTCH1 NICD fragment and
      exposed to either cortisol or vehicle. Cortisol opposed the induction of mRNA and
      heterogeneous nuclear RNA for Hey1, Hey2, and HeyL by DLL1, but had no effect on
      mRNA stability, indicating that glucocorticoids inhibit Hey expression by
      transcriptional mechanisms. Transactivation studies and electrophoretic mobility
      shift assays revealed that cortisol did not oppose RBPJ-mediated transcription or
      RBPJ/DNA interactions, respectively. In conclusion, glucocorticoids suppress
      expression of Hey1, Hey2, and HeyL in osteoblasts by RBPJ-independent
      transcriptional mechanisms.

PMID- 29575204
TI  - The adoption of care robots in home care-A survey on the attitudes of Finnish
      home care personnel.
AB  - AIMS AND OBJECTIVES: This article examines the attitudes of Finnish home care
      registered nurses, licensed vocational nurses and other health and social care
      personnel towards the introduction and use of care robots in home care.
      BACKGROUND: The significance of care robotics has been highlighted in recent
      years. However, personnel-related social psychological barriers to the
      introduction of care robots have been given very little study. DESIGN: Cross
      sectional study conducted by questionnaire. The theoretical framework of the
      study is based on Ajzen's theory of planned behaviour and the research discussion
      about attitudes towards robots. METHODS: The research data were collected in five
      municipalities in different parts of Finland in 2016, and the questionnaire was
      answered by a total of 200 home care workers. The research data were analysed
      using exploratory factor analysis, Pearson product-moment correlation, one-way
      analysis of variance and linear regression analysis. RESULTS: The results are
      consistent with Ajzen's theory and previous studies on the acceptance of
      information systems in health care. Personnel behavioural intentions related to
      the introduction of robot applications in home care are influenced by their
      personal appreciation of the usefulness of robots, the expectations of their
      colleagues and supervisors, as well as by their own perceptions of their capacity
      to learn to use care robots. In particular, personnel emphasised the value of
      care robots in providing reminders and guidance, as well as promoting the safety
      of the older people. CONCLUSIONS: The study shows that an intimate human-robot
      relationship can pose a challenge from the perspective of the acceptance of care
      robots. RELEVANCE TO CLINICAL PRACTICE: From the perspective of the introduction
      of care robots in home care, personnel training and the construction of a
      positive working atmosphere play a key role. In addition, the introduction of
      robots requires further consideration of a number of ethical issues.

PMID- 29575205
TI  - Estimate of choline nutritional requirements for chicks from 1 to 21 days of age.
AB  - Choline is an essential nutrient in poultry diets because it performs various
      important metabolic functions. The objective of this study was to re-evaluate the
      choline requirements of male broiler chickens from 1 to 21 days of age at two
      levels of methionine. Two assays using 2,160 Cobb(r) chickens (1,080 in each
      assay) were conducted. The study design was completely randomized and consisted
      of six treatments and six replicates, with 30 animals per experimental unit. The
      semipurified basal diet was formulated with corn, soya bean meal, soya protein
      concentrate, starch and sugar, providing 390 mg/kg choline and 0.593% digestible
      methionine (requirement level) in Assay 1 and a reduction of about one-quarter in
      the requirement level of digestible methionine (0.440%) in Assay 2. Choline
      chloride (62.5%) was added by a supplementation technique to both basal diets to
      compose crescent levels of choline supplementation (715, 1,040, 1,365, 1,690 and
      2,015 mg/kg). The weight gain responses were fitted using quadratic polynomial
      (QP) and broken-line (BL) models. The ideal intake of choline (mg/bird.day) was
      estimated from the first intercept of the QP with the BL plateau (BL + QP). The
      results showed that the diet with the 25% reduction in digestible methionine
      limited the maximum weight gain by approximately 10%. The choline requirements of
      broilers from 1 to 7, 1 to 14 and 1 to 21 days of age were 27,013, 44,458 and
      62,535 mg/bird.day, respectively, for the requirement level of digestible
      methionine and 26,796, 41,820 and 56,578 mg/bird.day for the broilers receiving
      the diet with the 25% reduction in digestible methionine.

PMID- 29575206
TI  - The fasciacytes: A new cell devoted to fascial gliding regulation.
AB  - Hyaluronan occurs between deep fascia and muscle, facilitating gliding between
      these two structures, and also within the loose connective tissue of the fascia,
      guaranteeing the smooth sliding of adjacent fibrous fascial layers. It also
      promotes the functions of the deep fascia. In this study a new class of cells in
      fasciae is identified, which we have termed fasciacytes, devoted to producing the
      hyaluronan-rich extracellular matrix. Synthesis of the hyaluronan-rich matrix by
      these new cells was demonstrated by Alcian Blue staining, anti-HABP (hyaluronic
      acid binding protein) immunohistochemistry, and transmission electron microscopy.
      Expression of HAS2 (hyaluronan synthase 2) mRNA by these cells was detected and
      quantified using real time RT-PCR. This new cell type has some features similar
      to fibroblasts: they are positive for the fibroblast marker vimentin and negative
      for CD68, a marker for the monocyte-macrophage lineage. However, they have
      morphological features distinct from classical fibroblasts and they express the
      marker for chondroid metaplasia, S-100A4. The authors suggest that these cells
      represent a new cell type devoted to the production of hyaluronan. Since
      hyaluronan is essential for fascial gliding, regulation of these cells could
      affect the functions of fasciae so they could be implicated in myofascial pain.
      Clin. Anat. 31:667-676, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29575207
TI  - Ruthenium-Catalyzed Selective C-C Coupling of Allylic Alcohols with Free Indoles:
      Influence of the Metal Catalyst.
AB  - Versatile reactive activities of allyl alcohols with free indoles in C-H
      functionalization reactions were investigated. Direct alkylation or cascade
      cyclization reactions could be selectively controlled based on the catalyst
      system: Ru(PPh3 )3 Cl2 provided C3-substituted beta-ketone indoles whereas [Ru(p
      cymene)Cl2 ]2 yielded cyclized indoles.

PMID- 29575208
TI  - The rural mother's experience of caring for a child with a chronic health
      condition: An integrative review.
AB  - AIMS AND OBJECTIVES: To identify and review the literature on rural mothers'
      experiences in caring for a child with a chronic health condition. BACKGROUND:
      Families living with a child who has a chronic health condition experience many
      challenges; these are often amplified for families living in rural areas, where
      issues such as the distance from services add further challenges the family must
      manage. Like many children, rural children with chronic health conditions are
      primarily cared for by their mothers. The additional strain of geography creates
      its own unique experiences for mothers who need to access the high-quality care
      that their child requires. DESIGN: Integrative literature review using the
      Equator PRISMA guidelines. METHODS: A search of databases; Cochrane, CINAHL,
      Ovid, PubMed, ProQuest Health and Medicine, Informit and Scopus for studies
      published between 2005-2016 using an integrative review approach. A total of
      1,484 studies were identified with an additional six studies found through
      snowballing. The search resulted in seven studies being meeting the inclusion
      criteria after using the Critical Appraisal Skills Programme. RESULTS: Data from
      the seven articles were analysed, and the mothers' experiences were synthesised
      into five themes: "struggling for resources," "barriers in accessing services,"
      "strain of decision-making," "mother's physical and emotional breakdown" and "the
      daily management of family activities". These five themes formed the basis of
      this article. CONCLUSIONS: The findings indicate that mothers from rural areas
      face additional barriers related to their rurality, including transportation
      difficulties, socioeconomic status and social isolation, and are challenged by
      limited access to specialty medical services, educators and allied health
      professionals. The literature review outcome will assist in informing nursing
      practice through identifying and allocating resources to reduce these barriers;
      rural mother experience will assist in enabling the child to reach their full
      developmental potential. RELEVANCE TO CLINICAL PRACTICE: There is a need for
      health professionals to understand the challenges and barriers rural mothers face
      in accessing services. Nurses can assist rural mothers to navigate and access the
      appropriate services in order to reduce health inequity, increase accessibility
      to services and reduce rural disadvantage for their child. Nurses and health
      professionals are in an ideal position to develop future models of care that
      optimise health outcomes and enable equity and access to services for rural
      children with chronic conditions similar to those experienced by their urban
      counterparts.

PMID- 29575209
TI  - Rapid Oligonucleotide Drug Impurity Determination by Direct Spectral Comparison
      of Ion Pair-Reversed Phase HPLC ESI MS Data.
AB  - RATIONALE: Quantitative Ion-Pair (IP)-HPLC MS methods are employed to determine
      the complex impurity profiles of oligonucleotide therapeutics. While impurities
      that co-elute with the main product are routinely monitored, the large number of
      early and late eluting impurities makes their individual measurements tedious and
      time-consuming. An improved method is needed for routine analyses. METHODS: A
      Combined Ranking (CR) index is developed to provide a composite value for both
      qualitative and quantitative impurity changes. Positive and Negative Impurity
      Change (PIC/NIC) indices are developed to determine the degree and direction of
      change. Optimized experimental conditions are determined for the characterization
      of trace levels of impurities. Replicate analysis, blank subtraction, and signal
      processing approaches are used to enhance the S/N. Dot-product and Euclidean
      distance equations monitor spectral changes. RESULTS: Spiking experiments with
      individual and complex impurity mixtures show the method can distinguish among
      samples differing in impurity content by 0.2% wt. The method has been applied to
      monitor changes in impurity profile among different batches of the same
      oligonucleotide and changes in the same batch over time (stability analysis). The
      method permits rapid determination of changes in the types and amounts (increases
      and decreases) of impurities present. CONCLUSIONS: A novel approach for the rapid
      determination of changes in the impurity profile of oligonucleotide therapeutics
      has been developed. The straightforward data treatment and the speed and
      simplicity of the approach make the method easy to implement and use. Possible
      quality control applications include drug substance and drug product stability
      studies, and the assessment of batch-to-batch variability.

PMID- 29575210
TI  - Delivering cognitive behavioural therapy to advanced cancer patients: A
      qualitative exploration into therapists' experiences within a UK psychological
      service.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) is commonly used to treat cancer
      patients with psychological disorders such as depression. There has been little
      qualitative research exploring the experience of therapists delivering CBT to
      patients with advanced cancer and long-term health conditions generally.
      Therapists' views may help identify difficulties in delivering therapy and how
      these may be overcome. The aim of this study was to inform practice by
      qualitatively exploring the experiences of therapists delivering CBT to patients
      with advanced cancer. DESIGN: Sixteen semi-structured interviews were conducted
      with therapists from Increasing Access to Psychological Therapy (IAPT) services
      in London, UK, who had delivered CBT to patients enrolled on the CanTalk trial.
      Interviews were recorded, transcribed, and analysed using framework analysis.
      RESULTS: Therapists reported positive experiences when working with the target
      population. Flexibility, adaptability, and a consideration of individual needs
      were identified as important when delivering CBT, but the rigidity of IAPT
      policies and demand for services were perceived as problematic. Although
      therapists reported adequate training, specialist supervision was desired when
      delivering therapy to this complex population. CONCLUSION: IAPT therapists can
      deliver CBT to advanced cancer patients, given therapists positive experiences
      evident in the present study. However, it was concluded that additional service
      and modifications of therapy may be needed before positive outcomes for both
      therapists and patients can be achieved.

PMID- 29575211
TI  - GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in
      astrocytes.
AB  - The prevalent view in neuroenergetics is that glucose is the main brain fuel,
      with neurons being mostly oxidative and astrocytes glycolytic. Evidence
      supporting that astrocyte mitochondria are functional has been overlooked. Here
      we sought to determine what is unique about astrocyte mitochondria by performing
      unbiased statistical comparisons of the mitochondriome in astrocytes and neurons.
      Using MitoCarta, a compendium of mitochondrial proteins, together with
      transcriptomes of mouse neurons and astrocytes, we generated cell-specific
      databases of nuclear genes encoding for mitochondrion proteins, ranked according
      to relative expression. Standard and in-house Gene Set Enrichment Analyses (GSEA)
      of five mouse transcriptomes revealed that genes encoding for enzymes involved in
      fatty acid oxidation (FAO) and amino acid catabolism are consistently more
      expressed in astrocytes than in neurons. FAO and oxidative-metabolism-related
      genes are also up-regulated in human cortical astrocytes versus the whole cortex,
      and in adult astrocytes versus fetal astrocytes. We thus present the first
      evidence of FAO in human astrocytes. Further, as shown in vitro, FAO coexists
      with glycolysis in astrocytes and is inhibited by glutamate. Altogether, these
      analyses provide arguments against the glucose-centered view of energy metabolism
      in astrocytes and reveal mitochondria as specialized organelles in these cells.

PMID- 29575212
TI  - Association between cervical lordotic curvature and cervical muscle cross
      sectional area in patients with loss of cervical lordosis.
AB  - Disruption of the cervical lordotic curve can cause undesirable symptoms such as
      neck pain, and cord compression. The purpose of this study was to investigate the
      biomechanics of loss of cervical lordosis by measuring the cross-sectional area
      (CSA) of the cervical muscles using magnetic resonance imaging (MRI), and to
      determine the relationship between cervical lordosis angle and cervical muscle
      status. The cervical lordosis angle was measured on standing lateral plain
      radiography using the posterior tangent technique in patients who complained of
      neck pain. The CSAs of the cervical flexor muscles including the longus cervicis
      and longus capitis, the cervical extensor muscles including the splenius capitis
      and semispinalis capitis, and the sternocleidomastoid muscle, were measured at
      the maximum levels by axial T1-weighted MRI. We compared neck muscle CSAs between
      the two groups, the correlation with cervical lordosis angle, and muscle status
      including CSA and imbalance. The CSA of the semispinalis capitis was
      significantly lower in the loss of cervical lordosis group, and the ratio of
      cervical flexor to extensor was significantly different between the two groups (P
      < 0.05). Partial correlation analysis revealed that the cervical lordotic angle
      was significantly positively correlated with the ratio of flexor to extensor
      muscle CSAs (P < 0.05). There is a significant relationship between cervical
      muscle imbalance, including extensor muscle weakness, and loss of cervical
      lordosis. An exercise program focusing on cervical extensor muscle strengthening
      and restoring the balance of flexor and extensor muscles is recommended for
      patients with loss of cervical lordosis. Clin. Anat. 31:710-715, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29575213
TI  - Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small
      pancreatic neuroendocrine tumors.
AB  - BACKGROUND AND AIM: Little is known about the standard care of small (<2 cm in
      diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study
      was to determine the clinical outcomes of small PNET after endoscopic ultrasound
      (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). METHODS: In this prospective
      cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled
      and were followed for >=3 years. Treatment efficacy was the primary outcome
      measure. RESULTS: In total, 33 patients who had 40 pathologically confirmed PNET
      (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA
      sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6
      sessions per tumor), which included 40 initial sessions and 23 repeated sessions
      owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture
      injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved
      in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%)
      sessions of EUS-ELA. Lipiodol retention within tumor had better treatment
      outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No
      malignancy or lymph node metastasis was discovered during a median follow up of
      42 months (IQR 39-46 months). CONCLUSIONS: We found that EUS-ELA was a safe and
      effective alternative option in the management of PNET <2.0 cm in diameter; 60%
      of patients achieved complete ablation. Lipiodol retention within tumor may be a
      useful early predictor of treatment effectiveness. Trial registered at
      ClinicalTrials.gov (NCT 01902238).

PMID- 29575214
TI  - The relationship between process use and stage of change for sugary drinks.
AB  - BACKGROUND: Decreasing sugar-sweetened beverage consumption may reduce obesity
      and obesity-related diseases. To better understand what processes could
      facilitate a reduction in sugary beverage intake, we examined the relationship
      between stage-of-change and use of 10 processes of change. Secondarily,
      reliability of the measure was assessed. METHODS: A cross-sectional study was
      conducted, using a newly developed stage-of-change and process of change
      questionnaire. Participants (n = 105; male, n = 28) were aged between 18 and 60
      years. A one-way analysis of variance, with Tukey's and Benjamini-Hochberg post
      hoc tests, was used to compare process use by stages. Paired t-tests were used to
      compare total cognitive and total behavioural process use within each stage.
      Cronbach's alpha coefficient and mean inter-item correlation was used to assess
      internal consistency. Reliability of repeated items was examined using kappa.
      RESULTS: Cognitive and behavioural processes were used more in the
      contemplation/preparation and maintenance stages than in precontemplation (all P
      < 0.05). Compared to precontemplation, process use was significantly higher in
      contemplation/preparation for five individual processes, action for four
      processes and maintenance for five processes. The use of dramatic relief and self
      liberation was lower in maintenance than contemplation/preparation. Across the
      stages, the use of eight of the 10 processes differed. The use of consciousness
      raising, self re-evaluation and self liberation differed between stages more
      frequently than other processes. CONCLUSIONS: The use of many processes differed
      by stage and could be incorporated into programmes aiming to assist adults in
      reducing their consumption of sugary drinks.

PMID- 29575215
TI  - Screening an elderly hearing impaired population for mild cognitive impairment
      using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment
      (MoCA).
AB  - OBJECTIVES: To determine if there is an association between hearing loss and
      poorer cognitive scores on Mini-Mental State Examination (MMSE) and Montreal
      Cognitive Assessment (MoCA) and to determine if poor hearing acuity affects
      scoring on the cognitive screening tests of MMSE and MoCA. METHODS: One hundred
      fourteen elderly patients (Singapore residents) aged between 55 and 86 years were
      sampled. Participants completed a brief history questionnaire, pure tone
      audiometry, and 2 cognitive screening tests-the MMSE and MoCA. Average hearing
      thresholds of the better ear in the frequencies of 0.5, 1, 2, and 4 kHz were used
      for data analysis. RESULTS: Hearing loss was significantly associated with poorer
      cognitive scores in Poisson regression models adjusted for age. Mini-Mental State
      Examination scores were shown to decrease by 2.8% (P = .029), and MoCA scores by
      3.5% (P = .013) for every 10 dB of hearing loss. Analysis of hearing-sensitive
      components of "Registration" and "Recall" in MMSE and MoCA using chi-square tests
      showed significantly poorer performance in the hearing loss group as compared to
      the normal hearing group. Phonetic analysis of target words with high error rates
      shows that the poor performance was likely contributed by decreased hearing
      acuity, on top of a possible true deficit in cognition in the hearing impaired.
      CONCLUSIONS: Hearing loss is associated with poorer cognitive scores on MMSE and
      MoCA, and cognitive scoring is likely confounded by poor hearing ability. This
      highlights an important, often overlooked aspect of sensory impairment during
      cognitive screening. Provisions should be made when testing for cognition in the
      hearing-impaired population to avoid over-referral and subsequent misdiagnoses of
      cognitive impairment.

PMID- 29575216
TI  - Variation in the association of Der p 1 and Der f 1 with asthma and rhinitis in 9
      11-year-old schoolchildren: The French six cities study.

PMID- 29575217
TI  - Association analysis of the genetic polymorphisms with leprosy subtypes in
      Chinese Han population from Northern China.

PMID- 29575218
TI  - Denise Kandel's classic work on the gateway sequence of drug acquisition.
AB  - During the early 1970s Denise Kandel and her colleagues documented an 'invariant
      sequence' in initiation of drug use: starting with alcohol and tobacco,
      progressing to cannabis and then to other illicit, or 'harder' drugs. This
      observation, which became known as the 'gateway sequence' of drug use, has been
      influential in policy debates but remains highly contentious, with the area of
      greatest controversy focusing upon whether cannabis use increases risk causally
      for initiation of other illicit drugs. While numerous studies have replicated
      Kandel's initial findings (sequence of onset) and reported that associations
      between cannabis use and the use of other illicit drugs remain after controlling
      for potentially confounding factors, the mechanisms underlying these observed
      associations remain hotly debated. In particular, it is possible that the
      observed associations are non-causal but reflect the influence of confounding
      factors which influence both early-onset drug use and subsequent progressions.
      However, research employing a range of techniques to address this issue has been
      unable to discount the possibility that associations between earlier and
      subsequent drug use reflect causal processes. This paper reviews Kandel's ongoing
      contributions to this field, which span 45 years, and discusses both the
      influence of her work and the controversy that it has aroused.

PMID- 29575219
TI  - The history of the Society of Urodynamics, Female Pelvic Medicine, and Urogenital
      Reconstruction.
AB  - AIMS: To review the history of the Society of Urodynamics, Female Pelvic Medicine
      and Urogenital Reconstruction (SUFU). METHODS: We reviewed Society meeting
      minutes, contacted all living former Society presidents, searched the William P.
      Didusch Center for Urology History records, and asked Society members to share
      their important Society experiences in order to gather important historical
      information about the Society. RESULTS: The Society initially formed as the
      Urodynamics Society in 1969 in the backdrop of a growing passion for scientific
      research in the country after World War II ended. Since then, Society meetings
      have provided a pivotal forum for the advancement of science in lower urinary
      tract dysfunction. Meetings occurred annually until 2004, when the meeting
      schedule increased to biannual. The journal, Neurourology and Urodynamics, became
      the official journal of the Society in 2005. SUFU has authored important
      guidelines on urodynamics (2012), non-neurogenic overactive bladder (2012), and
      stress urinary incontinence (2017) and has shared important collaborations with
      other societies, including the American Urological Association (AUA), the
      International Continence Society (ICS), and the International Society of Pelvic
      Neuromodulation (ISPiN). SUFU has also been instrumental in trainee education and
      helped to establish formal fellowship training in the field in addition to
      holding a yearly educational meeting for urology residents. The Society has been
      led by 21 presidents throughout its history. CONCLUSION: Throughout the Society's
      near half-century long existence, the Society has fostered research, published
      guidelines, and educated trainees in order to improve the care of individuals
      suffering from lower urinary tract dysfunction.

PMID- 29575220
TI  - Lumbosacral plexus root thickening: Establishing normal root dimensions using
      magnetic resonance neurography.
AB  - Disorders affecting the lumbosacral plexus (LSP) can alter root diameter. Our aim
      was to determine normal LSP nerve root dimensions using magnetic resonance
      neurography (MRN). Eleven asymptomatic patients (ages: 18-53, mean: 34 years)
      underwent MRN of the LSP on a 3 T scanner with an 8-channel torso-PA coil. IDEAL
      T2-weighted images were acquired and nerve root dimensions were measured from the
      second lumbar (L2) to the first sacral (S1) vertebrae on the coronal plane, 5 mm
      from the dorsal root ganglion (DRG). Root size was recorded by three separate
      groups of radiologists with different levels of expertise. Additional LSP-MRN
      images were acquired from a fresh-frozen cadaver specimen using the same scanner
      and parameters identical to those described above. Subsequently, two experienced
      anatomists dissected and measured the LSP roots at exactly the same distance from
      the DRG, using an electronic caliper. Mean root size values recorded (+/-
      standard deviation) in the asymptomatic patients were as follows: L2: 3.12 mm (+/
      0.92), L3: 4.29 mm (+/-0.95), L4: 5.13 mm (+/-0.79), L5: 5.29 mm (+/-0.9), and
      S1: 5.38 mm (+/-0.7). The correlation coefficients were 0.72 between the patient
      and cadaver MRN results and 0.79 between the patient and dissected cadaver MRN
      results. Inter-observer agreements were 0.73 among the radiologist groups and
      0.87 between the anatomists conducting dissections. We believe MRN provides
      reliable assessments of LSP root thickness. More extensive studies should be
      conducted to confirm the results described here. Clin. Anat. 31:782-787, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29575221
TI  - Arginine side chain stacking with peptide plane stabilizes the protein helix
      conformation in a cooperative way.
AB  - A combined experimental and computational study is performed for arginine side
      chain stacking with the protein alpha-helix. Theremostability measurements of
      Aristaless homeodomain, a helical protein, suggest that mutating the arginine
      residue R106, R137 or R141, which has the guanidino side chain stacking with the
      peptide plane, to alanine, destabilizes the protein. The R-PP stacking has an
      energy of ~0.2-0.4 kcal/mol. This stacking interaction mainly comes from
      dispersion and electrostatics, based on MP2 calculations with the energy
      decomposition analysis. The calculations also suggest that the stacking
      stabilizes 2 backbone-backbone h-bonds (i->i-4 and i-3->i-7) in a cooperative
      way. Desolvation and electrostatic polarization are responsible for cooperativity
      with the i->i-4 and i-3->i-7 h-bonds, respectively. This cooperativity is
      supported by a protein alpha-helices h-bond survey in the pdb databank where
      stacking shortens the corresponding h-bond distances.

PMID- 29575222
TI  - Use of a disposable ear speculum: An alternative technique for molluscum
      contagiosum curettage.
AB  - Molluscum contagiosum is a common contagious disease in children characterized by
      small skin-colored umbilicated papules. Although spontaneous resolution is
      common, many parents and patients seek treatment. Multiple therapeutic modalities
      have been described. We present an easy, safe, caregiver-friendly, modified
      curettage technique using an ear speculum.

PMID- 29575223
TI  - Novel side reaction accompanying cyclization of Glu(R1)-Glu(R2) dipeptides via
      lactamization of the Glu(R1) residue.
AB  - A series of linear peptides with the general formula H-Glu(R1)-Glu(R2)-OH was
      subjected to cyclization under standard conditions. Formation of respective 2,5
      diketopiperazines was accompanied by transformation of the N-terminal Glu(R1) to
      pyroglutamic acid residue. Even in the case R1 is an amino acid residue attached
      to the N-terminal gamma-carboxyl group, lactamization leads to its elimination.
      The observed reaction has not been reported so far in the literature.
      Correspondingly, an alternative route to Glu(R1)-Glu(R2)-containing 2,5
      diketopiperazines was applied to improve the overall yields.

PMID- 29575224
TI  - Oral psoriasis and SIBO: is there a link?

PMID- 29575225
TI  - Peanut agglutinin specifically binds to a sperm region between the nucleus and
      mitochondria in tunicates and sea urchins.
AB  - Peanut agglutinin (PNA) is an established marker of the mammalian acrosome.
      However, we observed that PNA specifically binds to a unique intracellular
      structure alongside the nucleus in ascidian sperm. Here, we characterize the PNA
      binding structure in sperm of marine invertebrates. PNA bound to the region
      between the mitochondrion and nucleus in spermatozoa of ascidians, sea urchins,
      and an appendicularian. However, PNA-binding substances were not exposed by the
      calcium ionophore ionomycin in three ascidian species, indicating that it is a
      distinct structure from the acrosome. Instead, the ascidian PNA-binding region
      was shed with the mitochondrion from the sperm head via an ionomycin-induced
      sperm reaction. The ascidian PNA-binding substance appeared to be solubilized
      with SDS, but not Triton X-100, describing its detergent resistance. Lectins, PHA
      L4 , SSA, and MAL-I were detected at an area similar to the PNA-binding region,
      suggesting that it contains a variety of glycans. The location and some of the
      components of the PNA-binding region were similar to known endoplasmic reticulum
      (ER)-derived structures, although the ER marker concanavalin A accumulated at an
      area adjacent to but not overlapping the PNA-binding region. Therefore, we
      conclude that ascidian sperm possess a non-acrosomal, Triton-resistant, glycan
      rich intracellular structure that may play a general role in reproduction of
      tunicates and sea urchins given its presence across a wide taxonomic range.

PMID- 29575227
TI  - Peroral cholangioscopy-guided laser lithotripsy to treat regional hepatolithiasis
      without stricture.

PMID- 29575226
TI  - Discontinuation and dose adjustment of metoprolol after metoprolol
      paroxetine/fluoxetine co-prescription in Dutch elderly.
AB  - PURPOSE: Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in
      metoprolol (a CYP2D6 substrate) users is common, but data on the clinical
      consequences of this drug-drug interaction are limited and inconclusive.
      Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the
      existing treatment with metoprolol on the discontinuation and dose adjustment of
      metoprolol among elderly. METHODS: We performed a cohort study using the
      University of Groningen IADB.nl prescription database (www.IADB.nl). We selected
      all elderly (>=60 years) who had ever been prescribed metoprolol and had a first
      co-prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or
      mirtazapine (negative control) from 1994 to 2015. The exposure group was
      metoprolol and paroxetine/fluoxetine co-prescription, and the other groups acted
      as controls. The outcomes were early discontinuation and dose adjustment of
      metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR)
      and 95% confidence intervals (CI). RESULTS: Combinations of metoprolol
      paroxetine/fluoxetine, metoprolol-citalopram, and metoprolol-mirtazapine were
      started in 528, 673, and 625 patients, respectively. Compared with metoprolol
      citalopram, metoprolol-paroxetine/fluoxetine was not significantly associated
      with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95%
      CI:0.77-1.48; OR = 0.87, 95% CI:0.57-1.33, respectively). In comparison with
      metoprolol-mirtazapine, metoprolol-paroxetine/fluoxetine was associated with a
      significant 43% relative increase in early discontinuation of metoprolol (OR =
      1.43, 95% CI:1.01-2.02) but no difference in the risk of dose adjustment.
      Stratified analysis by gender showed that women have a significantly high risk of
      metoprolol early discontinuation (OR = 1.62, 95% CI:1.03-2.53). CONCLUSION:
      Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for
      female older patients, is associated with the risk of early discontinuation of
      metoprolol.

PMID- 29575228
TI  - Herbal medicines in the treatment of psychiatric disorders: 10-year updated
      review.
AB  - This paper provides a 10-year update of the 2007 systematic review of herbal
      medicines studied in a broad range of psychiatric disorders, including
      depression, anxiety, obsessive-compulsive, seasonal affective, bipolar,
      psychotic, phobic, somatoform, and attention-deficit hyperactivity disorders.
      Ovid Medline, PubMed, and the Cochrane Library were searched for herbal medicines
      with both pharmacological and clinical evidence of psychotropic activity. This
      updated review now covers clinical trial evidence for 24 herbal medicines in 11
      psychiatric disorders. High-quality evidence was found to exist for the use of
      Piper methysticum (Kava), Passiflora spp. (passionflower) and Galphimia glauca
      (galphimia) for anxiety disorders; and Hypericum perforatum (St John's wort) and
      Crocus sativus (saffron) for major depressive disorder. Other encouraging herbal
      medicines with preliminary evidence include Curcuma longa (turmeric) in
      depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo
      biloba (ginkgo) as an adjunctive treatment in Schizophrenia. Although depression
      and anxiety are commonly researched, many other mental disorders still require
      further prospective investigation. Although the previous review suggested
      increasing the adjunctive study of select herbal medicines with pharmaceuticals,
      this was still only found to sparingly occur in research designs. Aside from
      this, future focus should involve the incorporation of more biomarker analysis,
      in particular pharmacogenomics, to determine genetic factors moderating response
      to herbal medicines.

PMID- 29575229
TI  - Differential expression and prognostic value of long non-coding RNA in HPV
      negative head and neck squamous cell carcinoma.
AB  - BACKGROUND: Long non-coding RNA (lncRNA) has emerged as a new avenue of interest
      due to its various biological functions in cancer. Abnormal expression of lncRNA
      has been reported in other malignancies but has been understudied in head and
      neck squamous cell carcinoma (HNSCC). METHODS: The lncRNA expression was
      interrogated via quantitative real-time polymerase chain reaction (qRT-PCR) array
      for 19 human papillomavirus (HPV)-negative HNSCC tumor-normal pairs. The Cancer
      Genome Atlas (TCGA) was used to validate these results. The association between
      differentially expressed lncRNA and survival outcomes was analyzed. RESULTS:
      Differential expression was validated for 5 lncRNA (SPRY4-IT1, HEIH, LUCAT1,
      LINC00152, and HAND2-AS1). There was also an inverse association between MEG3
      expression (not significantly differentially expressed in TCGA tumors but highly
      variable expression) and 3-year recurrence-free survival (RFS). CONCLUSION: We
      identified and validated differential expression of 5 lncRNA in HPV-negative
      HNSCC. Low MEG3 expression was associated with favorable 3-year RFS, although the
      significance of this finding remains unclear.

PMID- 29575230
TI  - Explorations and perspectives on the neurobiological bases of autism spectrum
      disorder.

PMID- 29575231
TI  - Phosphoproteomic profiling reveals ABA-responsive phosphosignaling pathways in
      Physcomitrella patens.
AB  - Abscisic acid (ABA) and its signaling system are important for land plants to
      survive in terrestrial conditions. Here, we took a phosphoproteomic approach to
      elucidate the ABA signaling network in Physcomitrella patens, a model species of
      basal land plants. Our phosphoproteomic analysis detected 4630 phosphopeptides
      from wild-type P. patens and two ABA-responsive mutants, a disruptant of group-A
      type-2C protein phosphatase (PP2C; ppabi1a/b) and AR7, a defective mutant in ARK,
      identified as an upstream regulator of SnRK2. Quantitative analysis detected 143
      ABA-responsive phosphopeptides in P. patens. The analysis indicated that SnRK2
      mediated phosphorylation and target motifs were partially conserved in
      bryophytes. Our data demonstrate that the PpSnRK2B and AREB/ABF-type
      transcription factors are phosphorylated in vivo in response to ABA under the
      control of ARK. On the other hand, our data also revealed the following: (i) the
      entire ABA-responsive phosphoproteome in P. patens is quite diverse; (ii) P.
      patens PP2C affects additional pathways other than the known ABA signaling
      pathway; and (iii) ARK is mainly involved in ABA signaling. Taken together, we
      propose that the core ABA signaling pathway is essential in all land plants;
      however, some ABA-responsive phosphosignaling uniquely developed in bryophytes
      during the evolutionary process.

PMID- 29575232
TI  - The impact of NarcotrendTM EEG-guided propofol administration on the speed of
      recovery from pediatric procedural sedation-A randomized controlled trial.
AB  - BACKGROUND: Propofol is often used for procedural sedation in children undergoing
      gastrointestinal endoscopy. Reliable assessment of the depth of hypnosis during
      the endoscopic procedure is challenging. Processed electroencephalography using
      the Narcotrend Index can help titrating propofol to a predefined sedation level.
      AIMS: The aim of this trial was to investigate the impact of Narcotrend Index
      guided titration of propofol delivery on the speed of recovery. METHODS:
      Children, aged 12-17 years, undergoing gastrointestinal endoscopy under
      procedural sedation, had propofol delivered via target controlled infusion either
      based on Narcotrend Index guidance (group NI) or standard clinical parameters
      (group C). Sedation was augmented with remifentanil in both study groups. The
      primary endpoint of this study was to compare the speed of fulfilling discharge
      criteria from the operating room between study groups. Major secondary endpoints
      were propofol consumption, discharge readiness from the recovery room, hypnotic
      depth as measured by the Narcotrend Index, and adverse events. RESULTS: Of the 40
      children included, data were obtainable from 37. The time until discharge
      readiness from the operating room was shorter in group NI than in group C, with a
      difference between medians of 4.76 minutes [95%CI 2.6 to 7.4 minutes]. The same
      accounts for recovery room discharge times; difference between medians 4.03
      minutes [95%CI 0.81 to 7.61 minutes]. Propofol consumption and the percentage of
      EEG traces indicating oversedation were higher in group C than in group NI. There
      were no significant adverse events in either study group. CONCLUSION: Narcotrend
      Index guidance of propofol delivery for deep sedation in children aged 12-17
      years, underdoing gastrointestinal endoscopy results in faster recovery, less
      drug consumption, and fewer episodes of oversedation than dosing propofol
      according to clinical surrogate parameters of depth of hypnosis. The results of
      this study provide additional evidence in favor of the safety profile of
      propofol/remifentanil for procedural sedation in adequately selected pediatric
      patients.

PMID- 29575233
TI  - Usefulness of a novel device (Nelaton Attachment) for the two-fingers method
      during colorectal endoscopic submucosal dissection.

PMID- 29575234
TI  - 3D-Printing Electrolytes for Solid-State Batteries.
AB  - Solid-state batteries have many enticing advantages in terms of safety and
      stability, but the solid electrolytes upon which these batteries are based
      typically lead to high cell resistance. Both components of the resistance
      (interfacial, due to poor contact with electrolytes, and bulk, due to a thick
      electrolyte) are a result of the rudimentary manufacturing capabilities that
      exist for solid-state electrolytes. In general, solid electrolytes are studied as
      flat pellets with planar interfaces, which minimizes interfacial contact area.
      Here, multiple ink formulations are developed that enable 3D printing of unique
      solid electrolyte microstructures with varying properties. These inks are used to
      3D-print a variety of patterns, which are then sintered to reveal thin,
      nonplanar, intricate architectures composed only of Li7 La3 Zr2 O12 solid
      electrolyte. Using these 3D-printing ink formulations to further study and
      optimize electrolyte structure could lead to solid-state batteries with
      dramatically lower full cell resistance and higher energy and power density. In
      addition, the reported ink compositions could be used as a model recipe for other
      solid electrolyte or ceramic inks, perhaps enabling 3D printing in related
      fields.

PMID- 29575235
TI  - Bone marrow or adipose tissue mesenchymal stem cells: Comparison of the
      therapeutic potentials in mice model of acute liver failure.
AB  - Acute liver failure (ALF) is a lethal disease with limited life-saving therapy.
      Because lack of whole organ donors for liver transplantation, a substitute
      treatment strategy is needed for these patients. Preclinical and clinical
      findings have proved that treatment with mesenchymal stem cells (MSCs) is
      beneficial for recovery from ALF. In this approach, however, the appropriate
      sources of these cells are unclear. In the present study, we investigated and
      compared the therapeutic potentials of bone marrow-mesenchymal stem cells (BM
      MSC) with those of adipose tissue (AT-MSC) in carbon tetrachloride (CCL4)-induced
      acute liver failure in mice. Murine BM- and AT-MSCs obtained from normal mice
      were cultured and labelled. The cells were transplanted to CCL4-induced ALF mice
      models intravenously. After cell transplantation, blood samples and liver tissues
      were collected daily for 72 h to analyze liver enzymes and liver histopathology,
      respectively. We found that survival rate of AT-MSC transplanted (AT-TR) mice was
      significantly higher than that of control (ALF) group. Liver histopathology was
      superior in the AT-TR mice, but not significantly, compared to that in BM-MSC
      transplanted (BM-TR) ones. Furthermore, in the AT-TR mice the level of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT), in some time points
      were significantly less than those of BM-TR. Taken together, these data suggest
      that in comparison to BM-MSC, AT-MSCs is an appropriate choice for cell therapy
      in the case of acute liver failure.

PMID- 29575236
TI  - DMC is not better than TMZ on intracranial anti-glioma effects.
AB  - Previous studies showed Demethoxycurcumin (DMC) has stronger anti-glioma and anti
      GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower
      toxicity than TMZ on nude mice. However, this conclusion was confirmed to be
      wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ
      treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected
      with U87MG-luc cells in the caudate nucleus of the brain and treated with DMC (30
      mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection. Bioluminescence
      imaging (BLI) was used to monitoring tumor growth and response to therapy.
      Western blot was used to detect the expression of p-Akt, cleaved-caspase-3 and
      Bax. The average value of BLI showed TMZ determined a significant tumor
      regression while DMC had a mild regression effect on tumor growth compared with
      control group. Immunohistochemistry for Ki67, proliferating cell nuclear antigen
      (PCNA), and TUNEL demonstrated that TMZ more effectively inhibited the expression
      of Ki67 and PCNA, and increased the ratio of TUNEL-positive cells in in situ
      tumor tissue. Western blot analysis also indicated that TMZ but not DMC more
      significantly decreased p-Akt and increased cleaved-caspase-3 and Bax
      expression.These findings suggested a fact that TMZ appear to be more effective
      in controlling the growth of glioblastoma than DMC in an orthotopic glioblastoma
      xenograft model.

PMID- 29575237
TI  - Improving Nelumbo nucifera genome assemblies using high-resolution genetic maps
      and BioNano genome mapping reveals ancient chromosome rearrangements.
AB  - Genetic and physical maps are powerful tools to anchor fragmented draft genome
      assemblies generated from next-generation sequencing. Currently, two draft
      assemblies of Nelumbo nucifera, the genomes of 'China Antique' and 'Chinese Tai
      zi', have been released. However, there is presently no information on how the
      sequences are assembled into chromosomes in N. nucifera. The lack of physical
      maps and inadequate resolution of available genetic maps hindered the assembly of
      N. nucifera chromosomes. Here, a linkage map of N. nucifera containing 2371 bin
      markers [217 577 single nucleotide polymorphisms (SNPs)] was constructed using
      restriction-site associated DNA sequencing data of 181 F2 individuals and
      validated by adding 197 simple sequence repeat (SSR) markers. Additionally, a
      BioNano optical map covering 86.20% of the 'Chinese Tai-zi' genome was
      constructed. The draft assembly of 'Chinese Tai-zi' was improved based on the
      BioNano optical map, showing an increase of the scaffold N50 from 0.989 to 1.48
      Mb. Using a combination of multiple maps, 97.9% of the scaffolds in the 'Chinese
      Tai-zi' draft assembly and 97.6% of the scaffolds in the 'China Antique' draft
      assembly were anchored into pseudo-chromosomes, and the centromere regions along
      the pseudo-chromosomes were identified. An evolutionary scenario was proposed to
      reach the modern N. nucifera karyotype from the seven ancestral eudicot
      chromosomes. The present study provides the highest-resolution linkage map, the
      optical map and chromosome level genome assemblies for N. nucifera, which are
      valuable for the breeding and cultivation of N. nucifera and future studies of
      comparative and evolutionary genomics in angiosperms.

PMID- 29575238
TI  - Additive and synergistic inhibition of mantle cell lymphoma cell growth by
      combining olaparib with ibrutinib.
AB  - Mantle cell lymphoma (MCL) presents a therapeutic challenge. The B cell targeting
      agent, ibrutinib, is currently one of the most effective second-line therapies
      for MCL, but frequently leads to development of drug resistance, and short
      overall survival time upon relapse. Olaparib targets tumor cells with
      deficiencies in single-strand DNA break repair and thus may slow the development
      of genetic drug resistance. We found that the olaparib-ibrutinib combination
      significantly inhibits cell culture growth compared to either drug alone in two
      genetically distinct MCL cell lines. Moreover, these inhibitory effects are
      either additive or synergistic, depending on genetic background. Culture growth
      is inhibited due to increases in apoptosis, cell death, and cell cycle arrest,
      and the magnitude of each is cell line dependent. The additive and synergistic
      inhibition of this combination additionally supports a therapeutic strategy
      involving lower dosing of each drug to reduce potential side effects.

PMID- 29575239
TI  - An evaluation of serum gentamicin concentrations and bacterial susceptibility to
      gentamicin in equine practice.
AB  - BACKGROUND: Therapeutic drug monitoring and minimum inhibitory concentration
      (MIC) data allow more informed use of gentamicin. HYPOTHESIS/OBJECTIVES: To
      measure peak and trough serum gentamicin concentrations in horses after a 6.6
      mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which
      gentamicin might be selected. METHODS: Retrospective analysis of hospital
      records. Peak and trough plasma gentamicin concentrations were measured after 6.6
      mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was
      measured for 503 isolates from ambulatory practice and 33 from hospital practice.
      The distribution of gentamicin concentrations and MIC results were compared to
      current recommendations for MIC breakpoints. RESULTS: The median serum gentamicin
      concentration at 60 minutes after administration (C60min ) was 21.4 MUg/mL with a
      distribution indicating that bacteria with MIC >=2 MUg/mL were unlikely to be
      exposed to sufficient gentamicin for effective killing. Approximately 90% of
      isolates from ambulatory practice and 36% of hospital isolates had MICs at or
      below breakpoints for susceptibility with most of the remainder unlikely to be
      responsive, even to higher IV doses. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Gentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the
      majority of infections encountered in ambulatory practice, but less effective in
      an equine hospital. Because there was a dichotomy of most bacteria as being
      clearly susceptible or clearly resistant to gentamicin, it appears unlikely that
      higher doses would have been more efficacious, especially in the hospitalized
      population in our study.

PMID- 29575240
TI  - Role of p38 MAPK in disease relapse and therapeutic resistance by maintenance of
      cancer stem cells in head and neck squamous cell carcinoma.
AB  - AIM: This study aimed to investigate the role of p38 MAPK in maintenance of
      cancer stem cell (CSC) phenotype, therapy resistance, and DNA damage repair and
      response in head and neck squamous cell carcinoma (HNSCC). METHODS: In this
      study, 104 HNSCC patients were included. Western blot, immunohistochemistry, and
      qPCR analysis were performed to investigate the expression level of p-p38 and CSC
      markers in cut margin and tumor area of HNSCC patients. The expression level of p
      p38 and CSC markers was also evaluated in HNSCC cells with or without p38
      inhibitor. Chemoresistance, wound healing capacity, and multicellular tumor
      spheroids (MCTS) formation capacity were evaluated in HNSCC-derived cell lines
      with or without p38 inhibitor. In addition, DNA damage response and repair
      capacities were also evaluated in HNSCC cells after p38 inhibition using alkaline
      comet assay and gamma-H2 AX immunostaining. RESULT: We observed that recurrence
      could be associated with upregulated status of p-p38 and p38alpha gene in cut
      margin area of HNSCC patients as compared to tumor region. p38-inhibited cells
      showed significantly reduced expression of CSC markers, chemosensitivity toward
      cisplatin, reduced migration potential, and sphere-forming ability along with
      increased apoptotic population after treatment with increasing concentration of
      cisplatin. p38-inhibited cells also exhibited significantly increased comet olive
      tail moment and accumulation of gamma-H2 AX, demonstrating increased DNA damage.
      CONCLUSION: This study demonstrated that p38 MAPK activation may play a role in
      therapeutic resistance and disease relapse in HNSCC by maintenance of CSCs
      phenotype.

PMID- 29575241
TI  - Randomized controlled feasibility trial of supported self-management in adults
      with Type 2 diabetes mellitus and an intellectual disability: OK Diabetes.
AB  - AIMS: To undertake a feasibility randomized controlled trial of supported self
      management vs treatment as usual in a population of adults with obesity, Type 2
      diabetes and an intellectual disability. METHODS: We conducted an individually
      randomized feasibility trial. Participants were adults aged >18 years with a mild
      or moderate intellectual disability, living in the community with Type 2
      diabetes, on any therapy other than insulin. Participants had mental capacity to
      consent to research and the intervention. Inclusion criteria included HbA1c > 48
      mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below
      national guideline levels. The experimental intervention was standardized
      supported self-management delivered by diabetes specialist nurses plus treatment
      as usual, compared with treatment as usual alone. Feasibility outcomes included:
      recruitment and retention; intervention acceptability and feasibility; data
      collection and completeness for physiological state and values for candidate
      primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of
      those contacted and eligible) were randomized. All supported self-management
      sessions were completed by 35/41 participants (85%); only four completed no
      sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were
      obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean
      baseline HbA1c was 56+/-16.5 mmol/mol (7.3+/-1.5%) and the mean BMI was 34+/-7.6
      kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to
      have blood taken for outcome measurement was good. A definitive randomized
      controlled trial is feasible in this population. (Trial registration: Current
      Controlled Trials ISRCTN41897033).

PMID- 29575243
TI  - Direct cholangioscopic perspective on cholecystitis.

PMID- 29575242
TI  - Methodology for computing the burden of disease of adverse events following
      immunization.
AB  - PURPOSE: Composite disease burden measures such as disability-adjusted life-years
      (DALY) have been widely used to quantify the population-level health impact of
      disease or injury, but application has been limited for the estimation of the
      burden of adverse events following immunization. Our objective was to assess the
      feasibility of adapting the DALY approach for estimating adverse event burden.
      METHODS: We developed a practical methodological framework, explicitly describing
      all steps involved: acquisition of relative or absolute risks and background
      event incidence rates, selection of disability weights and durations, and
      computation of the years lived with disability (YLD) measure, with appropriate
      estimation of uncertainty. We present a worked example, in which YLD is computed
      for 3 recognized adverse reactions following 3 childhood vaccination types, based
      on background incidence rates and relative/absolute risks retrieved from the
      literature. RESULTS: YLD provided extra insight into the health impact of an
      adverse event over presentation of incidence rates only, as severity and duration
      are additionally incorporated. As well as providing guidance for the deployment
      of DALY methodology in the context of adverse events associated with vaccination,
      we also identified where data limitations potentially occur. CONCLUSIONS: Burden
      of disease methodology can be applied to estimate the health burden of adverse
      events following vaccination in a systematic way. As with all burden of disease
      studies, interpretation of the estimates must consider the quality and accuracy
      of the data sources contributing to the DALY computation.

PMID- 29575244
TI  - Attachment and alexithymia in adolescents with food allergy: A developmental
      hypothesis.

PMID- 29575246
TI  - Semantically defined subdomains of functional neuroimaging literature and their
      corresponding brain regions.
AB  - The functional neuroimaging literature has become increasingly complex and thus
      difficult to navigate. This complexity arises from the rate at which new studies
      are published and from the terminology that varies widely from study-to-study and
      even more so from discipline-to-discipline. One way to investigate and manage
      this problem is to build a "semantic space" that maps the different vocabulary
      used in functional neuroimaging literature. Such a semantic space will also help
      identify the primary research domains of neuroimaging and their most commonly
      reported brain regions. In this work, we analyzed the multivariate semantic
      structure of abstracts in Neurosynth and found that there are six primary domains
      of the functional neuroimaging literature, each with their own preferred reported
      brain regions. Our analyses also highlight possible semantic sources of reported
      brain regions within and across domains because some research topics (e.g.,
      memory disorders, substance use disorder) use heterogeneous terminology.
      Furthermore, we highlight the growth and decline of the primary domains over
      time. Finally, we note that our techniques and results form the basis of a
      "recommendation engine" that could help readers better navigate the neuroimaging
      literature.

PMID- 29575245
TI  - Long-term renal tubular damage in intrauterine growth-restricted rats.
AB  - BACKGROUND: Intrauterine growth restriction (IUGR) has been shown to be
      associated with increased risk of renal disease or hypertension in later life.
      Glomerular dysfunction, however, has mainly been reported, and limited
      information is available to link IUGR with renal tubular damage. The aim of this
      study was therefore to investigate urinary markers of tubular damage in a rat
      model of IUGR induced by bilateral uterine artery ligation. METHODS: Pregnant
      Sprague-Dawley rats underwent bilateral uterine artery ligation, while the
      control group underwent sham surgery. RESULTS: Birthweight was reduced, and
      urinary beta2-microglobulin (beta2-MG)-, cystatin C (Cys-C)-, and calbindin-to
      creatinine ratios were significantly higher at weeks 4 and 8 in the IUGR group
      compared with the control group. These urinary markers were not significantly
      different at week 16 between the two groups. Increased excretion of urinary beta2
      MG, Cys-C, and calbindin was observed in IUGR rats at >=8 weeks of age.
      CONCLUSION: Children born with IUGR are at increased risk for renal tubular
      damage.

PMID- 29575247
TI  - RbpA and sigmaB association regulates polyphosphate levels to modulate
      mycobacterial isoniazid-tolerance.
AB  - To facilitate survival under drug stresses, a small population of Mycobacterium
      tuberculosis can tolerate bactericidal concentrations of drugs without genetic
      mutations. These drug-tolerant mycobacteria can be induced by environmental
      stresses and contribute to recalcitrant infections. However, mechanisms
      underlying the development of drug-tolerant mycobacteria remain obscure. Herein,
      we characterized a regulatory pathway which is important for the tolerance to
      isoniazid (INH) in Mycobacterium smegmatis. We found that the RNA polymerase
      binding protein RbpA associates with the stress response sigma factor sigmaB , to
      activate the transcription of ppk1, the gene encoding polyphosphate kinase.
      Subsequently, intracellular levels of inorganic polyphosphate increase to promote
      INH-tolerant mycobacteria. Interestingly, sigmaB and ppk1 expression varied
      proportionately in mycobacterial populations and positively correlated with
      tolerance to INH in individual mycobacteria. Moreover, sigB and ppk1
      transcription are both induced upon nutrient depletion, a condition that
      stimulates the formation of INH-tolerant mycobacteria. Over-expression of ppk1 in
      rbpA knockdown or sigB deleted strains successfully restored the number of INH
      tolerant mycobacteria under both normal growth and nutrient starved conditions.
      These data suggest that RbpA and sigmaB regulate ppk1 expression to control drug
      tolerance both during the logarithmic growth phase and under the nutrition
      starved conditions.

PMID- 29575248
TI  - A High-yield Fall Risk and Adverse Events Screening Questions From the Stopping
      Elderly Accidents, Death, and Injuries (STEADI) Guideline for Older Emergency
      Department Fall Patients.
AB  - OBJECTIVES: The objectives were to examine whether responses to the Stopping
      Elderly Accidents, Death, and Injuries (STEADI) questions responses predicted
      adverse events after an older adult emergency department (ED) fall visits and to
      identify factors associated with such recurrent fall. METHODS: We conducted a
      prospective study at two urban, teaching hospitals. We included patients aged >=
      65 years who presented to the ED for an accidental fall. Data were gathered for
      fall-relevant comorbidities, high-risk medications for falls, and the responses
      to 12 questions from the STEADI guideline recommendation. Our outcomes were the
      number of 6-month adverse events that were defined as mortality, ED revisit,
      subsequent hospitalization, recurrent falls, and a composite outcome. RESULTS:
      There were 548 (86.3%) patients who completed follow-up and 243 (44.3%) patients
      experienced an adverse event after a fall within 6 months. In multivariate
      analysis, seven questions from the STEADI guideline predicted various outcomes.
      The question "Had previous fall" predicted recurrent falls (odds ratio [OR] =
      2.45, 95% confidence interval [CI] = 1.52 to 3.97), the question "Feels unsteady
      when walking sometimes" (OR = 2.34, 95% CI = 1.44 to 3.81), and "Lost some
      feeling in their feet" predicted recurrent falls. In addition to recurrent falls
      risk, the supplemental questions "Use or have been advised to use a cane or
      walker," "Take medication that sometimes makes them feel light-headed or more
      tired than usual," "Take medication to help sleep or improve mood," and "Have to
      rush to a toilet" predicted other outcomes. CONCLUSION: A STEADI score of >=4 did
      not predict adverse outcomes although seven individual questions from the STEADI
      guidelines were associated with increased adverse outcomes within 6 months. These
      may be organized into three categories (previous falls, physical activity, and
      high-risk medications) and may assist emergency physicians to evaluate and refer
      high-risk fall patients for a comprehensive falls evaluation.

PMID- 29575249
TI  - Separate neural representations of prediction error valence and surprise:
      Evidence from an fMRI meta-analysis.
AB  - Learning occurs when an outcome differs from expectations, generating a reward
      prediction error signal (RPE). The RPE signal has been hypothesized to
      simultaneously embody the valence of an outcome (better or worse than expected)
      and its surprise (how far from expectations). Nonetheless, growing evidence
      suggests that separate representations of the two RPE components exist in the
      human brain. Meta-analyses provide an opportunity to test this hypothesis and
      directly probe the extent to which the valence and surprise of the error signal
      are encoded in separate or overlapping networks. We carried out several meta
      analyses on a large set of fMRI studies investigating the neural basis of RPE,
      locked at decision outcome. We identified two valence learning systems by pooling
      studies searching for differential neural activity in response to categorical
      positive-versus-negative outcomes. The first valence network (negative >
      positive) involved areas regulating alertness and switching behaviours such as
      the midcingulate cortex, the thalamus and the dorsolateral prefrontal cortex
      whereas the second valence network (positive > negative) encompassed regions of
      the human reward circuitry such as the ventral striatum and the ventromedial
      prefrontal cortex. We also found evidence of a largely distinct surprise-encoding
      network including the anterior cingulate cortex, anterior insula and dorsal
      striatum. Together with recent animal and electrophysiological evidence this meta
      analysis points to a sequential and distributed encoding of different components
      of the RPE signal, with potentially distinct functional roles.

PMID- 29575250
TI  - Reducing Architecture Limitations for Efficient Blue Perovskite Light-Emitting
      Diodes.
AB  - Light-emitting diodes utilizing perovskite nanocrystals have generated strong
      interest in the past several years, with green and red devices showing high
      efficiencies. Blue devices, however, have lagged significantly behind. Here, it
      is shown that the device architecture plays a key role in this lag and that NiOx
      , a transport layer in one of the highest efficiency devices to date, causes a
      significant reduction in perovskite luminescence lifetime. An alternate transport
      layer structure which maintains robust nanocrystal emission is proposed. Devices
      with this architecture show external quantum efficiencies of 0.50% at 469 nm,
      seven times higher than state-of-the-art devices at that wavelength. Finally, it
      is demonstrated that this architecture enables efficient devices across the
      entire blue-green portion of the spectrum. The improvements demonstrated here
      open the door to efficient blue perovskite light-emitting diodes.

PMID- 29575251
TI  - Treatment for moderate to severe atopic dermatitis in alpine and moderate
      maritime climates differentially affects helper T cells and memory B cells in
      children.
AB  - BACKGROUND: Treatment of atopic dermatitis (AD) is focused on topical anti
      inflammatory therapy, epidermal barrier repair and trigger avoidance.
      Multidisciplinary treatment in both moderate maritime and alpine climates can
      successfully reduce disease activity in children with AD. However, it remains
      unclear whether abnormalities in B cell and T cell memory normalize and whether
      this differs between treatment strategies. OBJECTIVE: To determine whether
      successful treatment in maritime and alpine climates normalizes B- and T
      lymphocytes in children with moderate to severe AD. METHODS: The study was
      performed in the context of a trial (DAVOS trial, registered at Current
      Controlled Trials ISCRTN88136485) in which eighty-eight children with moderate to
      severe AD were randomized to 6 weeks of treatment in moderate maritime climate
      (outpatient setting) or in the alpine climate (inpatient setting). Before and
      directly after treatment, disease activity was determined with SA-EASI and serum
      TARC, and T cell and B cell subsets were quantified in blood. RESULTS: Both
      treatment protocols achieved a significant decrease in disease activity, which
      was accompanied by a reduction in circulating memory Treg, transitional B cell
      and plasmablast numbers. Alpine climate treatment had a significantly greater
      effect on disease activity and was accompanied by a reduction in blood
      eosinophils and increases in memory B cells, CD8+ TemRO, CD4+ Tcm and CCR7+ Th2
      subsets. CONCLUSIONS AND CLINICAL RELEVANCE: Clinically successful treatment of
      AD induces changes in blood B- and T cell subsets reflecting reduced chronic
      inflammation. In addition, multidisciplinary inpatient treatment in the alpine
      climate specifically affects memory B cells, CD8+ T cells and Th2 cells. These
      cell types could represent good markers for treatment efficacy.

PMID- 29575252
TI  - Decomposition of cyanobacterial light harvesting complexes: NblA-dependent role
      of the bilin lyase homolog NblB.
AB  - Phycobilisomes, the macromolecular light harvesting complexes of cyanobacteria
      are degraded under nutrient-limiting conditions. This crucial response is
      required to adjust light excitation to the metabolic status and avoid damage by
      excess excitation. Phycobilisomes are comprised of phycobiliproteins, apo
      proteins that covalently bind bilin chromophores. In the cyanobacterium
      Synechococcus elongatus, the phycobiliproteins allophycocyanin and phycocyanin
      comprise the core and the rods of the phycobilisome, respectively. Previously,
      NblB was identified as an essential component required for phycocyanin
      degradation under nutrient starvation. This protein is homologous to bilin
      lyases, enzymes that catalyze the covalent attachment of bilins to apo-proteins.
      However, the nblB-inactivated strain is not impaired in phycobiliprotein
      synthesis, but rather is characterized by aberrant phycocyanin degradation. Here,
      using a phycocyanin-deficient strain, we demonstrate that NblB is required for
      degradation of the core pigment, allophycocyanin. Furthermore, we show that the
      protein NblB is expressed under nutrient sufficient conditions, but during
      nitrogen starvation its level decreases about two-fold. This finding is in
      contrast to an additional component essential for degradation, NblA, the
      expression of which is highly induced under starvation. We further identified
      NblB residues required for phycocyanin degradation in vivo. Finally, we
      demonstrate phycocyanin degradation in a cell-free system, thereby providing
      support for the suggestion that NblB directly mediates pigment degradation by
      chromophore detachment. The dependence of NblB function on NblA revealed using
      this system, together with the results indicating presence of NblB under nutrient
      sufficient conditions, suggests a rapid mechanism for induction of pigment
      degradation, which requires only the expression of NblA.

PMID- 29575253
TI  - Conservation of a domestic metapopulation structured into related and partly
      admixed strains.
AB  - Preservation of genetic diversity is one of the most pressing challenges in the
      planetary boundaries concept. Within this context, we focused on genetic
      diversity in a native, unselected and highly admixed domesticated metapopulation.
      A set of 1,828 individuals from 60 different cattle breeds was analysed using a
      medium density SNP chip. Among these breeds, 14 Busa strains formed a
      metapopulation represented by 350 individuals, while the remaining 46 breeds
      represented the global cattle population. Genetic analyses showed that the
      scarcely selected and less differentiated Busa metapopulation contributed a
      substantial proportion (52.6%) of the neutral allelic diversity to this global
      taurine population. Consequently, there is an urgent need for synchronized
      maintenance of this highly fragmented domestic metapopulation, which is
      distributed over several countries without sophisticated infrastructure and
      highly endangered by continuous replacement crossing as part of the global
      genetic homogenization process. This study collected and evaluated samples, data
      and genomewide information and developed genome-assisted cross-border
      conservation concepts. To detect and maintain genetic integrity of the
      metapopulation strains, we designed and applied a composite test that combines
      six metrics based on additive genetic relationships, a nearest neighbour graph
      and the distribution of semiprivate alleles. Each metric provides distinct
      information components about past admixture events and offers an objective and
      powerful tool for the detection of admixed outliers. The here developed
      conservation methods and presented experiences could easily be adapted to
      comparable conservation programmes of domesticated or other metapopulations bred
      and kept in captivity or under some other sort of human control.

PMID- 29575254
TI  - Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for
      uterine cervical cancer with lymph node metastasis.
AB  - The purpose of this phase II trial was to assess the efficacy and toxicity of
      paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy
      for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO
      stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled.
      Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175
      mg/m2 and nedaplatin at 80 mg/m2 were administered every 28-day cycle, of which
      there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled
      in the study from November 2011 to July 2015. Their median age was 48.5 years
      (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients
      (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%)
      had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months
      (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival
      rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%),
      respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse
      events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were
      neutropenia (60.7%) and infection (6.6%). The proportion of patients who
      completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy
      with TN for cervical cancer with LNM was demonstrated to be an effective and
      feasible treatment. A phase III trial is warranted to compare this with
      concurrent chemoradiotherapy.

PMID- 29575255
TI  - Multidimensional Synergistic Nanoarchitecture Exhibiting Highly Stable and
      Ultrafast Sodium-Ion Storage.
AB  - Conversion-type anodes with multielectron reactions are beneficial for achieving
      a high capacity in sodium-ion batteries. Enhancing the electron/ion conductivity
      and structural stability are two key challenges in the development of high
      performance sodium storage. Herein, a novel multidimensionally assembled
      nanoarchitecture is presented, which consists of V2 O3 nanoparticles embedded in
      amorphous carbon nanotubes that are then coassembled within a reduced graphene
      oxide (rGO) network, this materials is denoted V2 O3 ?C-NTs?rGO. The selective
      insertion and multiphase conversion mechanism of V2 O3 in sodium-ion storage is
      systematically demonstrated for the first time. Importantly, the naturally
      integrated advantages of each subunit synergistically provide a robust structure
      and rapid electron/ion transport, as confirmed by in situ and ex situ
      transmission electron microscopy experiments and kinetic analysis. Benefiting
      from the synergistic effects, the V2 O3 ?C-NTs?rGO anode delivers an ultralong
      cycle life (72.3% at 5 A g-1 after 15 000 cycles) and an ultrahigh rate
      capability (165 mAh g-1 at 20 A g-1 , ~30 s per charge/discharge). The
      synergistic design of the multidimensionally assembled nanoarchitecture produces
      superior advantages in energy storage.

PMID- 29575256
TI  - Towards Useful Boronates through Atom-Economical Catalyzed Cascade Reactions.
AB  - Metal-catalyzed borylative cyclization reactions of polyunsaturated compounds
      allow concomitant formation of C-C and C-B bonds to provide cyclic boronates,
      which constitute synthetically useful intermediates. Recent developments using
      first-row transition metals as catalysts provide fully atom-economical reactions
      that follow mechanisms involving sigma-bond metathesis.

PMID- 29575257
TI  - Variation in proteomics and metabolomics of chicken hepatocytes exposed to medium
      with or without folic acid.
AB  - Hepatocytes are suitable models for metabolism study. Combined proteomics and
      metabolomics approaches should provide a comprehensive understanding for the
      effect of folic acid on hepatic metabolism in vitro. Primary chicken liver cells
      were exposed to medium with or without folic acid. The combined analyses
      uncovered 61 differential proteins and 43 differential metabolites between groups
      with or without folic acid in culture medium. Further pathway annotations
      revealed that RNA transport, protein processing, TCA cycle, glycolysis, pyruvate
      metabolism, and so on were significantly enriched. Meanwhile, lipid metabolism
      was enhanced in no folic acid group along with higher adipose triglyceride
      lipase, and 2-hydroxybutyric acid level. Concomitantly, amino acid, and
      carbohydrates metabolism were disturbed. Some amino acids level were changed as
      well as sugar-acids and sugar-alcohols. In addition, antioxidant function was
      altered resulting from perturbation of glutathione metabolism, glutamate, and
      cysteine metabolism. In conclusion, our results indicated that folic acid might
      affect antioxidant function and metabolism of lipid, amino acid, and
      carbohydrates in primary chicken hepatocytes via integrating proteomics, and
      metabolomics analyses method. These results may provide an insight into the
      effect of folic acid on hepatic metabolism in future research direction.

PMID- 29575258
TI  - Excitonic Properties of Chemically Synthesized 2D Organic-Inorganic Hybrid
      Perovskite Nanosheets.
AB  - 2D organic-inorganic hybrid perovskites (OIHPs) represent a unique class of
      materials with a natural quantum-well structure and quasi-2D electronic
      properties. Here, a versatile direct solution-based synthesis of mono- and few
      layer OIHP nanosheets and a systematic study of their electronic structure as a
      function of the number of monolayers by photoluminescence and absorption
      spectroscopy are reported. The monolayers of various OIHPs are found to exhibit
      high electronic quality as evidenced by high quantum yield and negligible Stokes
      shift. It is shown that the ground exciton peak blueshifts by ~40 meV when the
      layer thickness reduces from bulk to monolayer. It is also shown that the exciton
      binding energy remains effectively unchanged for (C6 H5 (CH2 )2 NH3 )2 PbI4 with
      the number of layers. Similar trends are observed for (C4 H9 NH3 )2 PbI4 in
      contrast to the previous report. Further, the photoluminescence lifetime is found
      to decrease with the number of monolayers, indicating the dominant role of
      surface trap states in nonradiative recombination of the electron-hole pairs.

PMID- 29575259
TI  - Crocin improves renal function by declining Nox-4, IL-18, and p53 expression
      levels in an experimental model of diabetic nephropathy.
AB  - Oxidative damage, inflammation and apoptosis play significant roles in diabetic
      nephropathy. Previous studies demonstrated anti-inflammatory and anti-oxidative
      effects of crocin, but there is no evidence about its effects on IL-18, NOX-4,
      and p53 expression in diabetic kidneys. The aim of this study was to evaluate
      possible effects of crocin on improving main mechanisms underlying diabetic
      nephropathy. Male Wistar rats were randomly divided into four separate groups as
      normal (C), normal treated (CC), diabetic (D), and diabetic treated (DC) (n = 6).
      Diabetes was induced by a single dose of streptozotocin (40 mg/kg/intravenous).
      Treated groups received crocin (40 mg/kg, intraperitoneal) for 8 weeks. At the
      end of the 8th week of the study, all rats were sacrificed and urine, blood and
      tissue were collected. Levels of urea, uric acid, creatinine and glucose were
      determined collected sera, and proteinuria was measured in urine samples.
      Moreover, the contents of malondialdehyde (MDA), nitrate, and glutathione (GLT)
      as well as catalase (CAT) and superoxide dismutase (SOD) enzymes activities were
      measured. The expression of NOX-4, IL-18, and p53 at both mRNA and protein levels
      were also assessed. Hyperglycemia significantly increased proteinuria in diabetic
      rats (D). Also, depressed antioxidant defense system potency, but increased NOX-4
      expression and free radicals production resulting in oxidative stress, were
      observed. Moreover, expressions of IL-18 (as a marker of inflammation) and p53
      (as a marker of apoptosis) were increased. These outcomes were accompanied by
      enhanced histological damages and renal failure but, treatment with crocin
      improved these deteriorations, and ameliorated renal function. It potentiated
      renal cells antioxidant defense system and declined inflammation. Also, crocin
      lowered apoptosis and improved histological damages in renal cells. Oxidative
      stress, inflammation and apoptosis are considered three main mechanisms
      underlying diabetic nephropathy. Treatment with crocin prevented these
      deleterious effects and improved renal function under diabetic conditions.

PMID- 29575260
TI  - The joint evolution of the Myxozoa and their alternate hosts: A cnidarian recipe
      for success and vast biodiversity.
AB  - The relationships between parasites and their hosts are intimate, dynamic and
      complex; the evolution of one is inevitably linked to the other. Despite multiple
      origins of parasitism in the Cnidaria, only parasites belonging to the Myxozoa
      are characterized by a complex life cycle, alternating between fish and
      invertebrate hosts, as well as by high species diversity. This inspired us to
      examine the history of adaptive radiations in myxozoans and their hosts by
      determining the degree of congruence between their phylogenies and by timing the
      emergence of myxozoan lineages in relation to their hosts. Recent genomic
      analyses suggested a common origin of Polypodium hydriforme, a cnidarian parasite
      of acipenseriform fishes, and the Myxozoa, and proposed fish as original hosts
      for both sister lineages. We demonstrate that the Myxozoa emerged long before
      fish populated Earth and that phylogenetic congruence with their invertebrate
      hosts is evident down to the most basal branches of the tree, indicating
      bryozoans and annelids as original hosts and challenging previous evolutionary
      hypotheses. We provide evidence that, following invertebrate invasion, fish hosts
      were acquired multiple times, leading to parallel cospeciation patterns in all
      major phylogenetic lineages. We identify the acquisition of vertebrate hosts that
      facilitate alternative transmission and dispersion strategies as reason for the
      distinct success of the Myxozoa, and identify massive host specification-linked
      parasite diversification events. The results of this study transform our
      understanding of the origins and evolution of parasitism in the most basal
      metazoan parasites known.

PMID- 29575261
TI  - Using the Internet for collateral information in forensic mental health
      evaluations.
AB  - There is a burgeoning literature regarding using Internet-based data in
      employment, university admissions, and healthcare settings, but such pertaining
      to forensic mental health assessment (FMHA) contexts is only beginning to develop
      and professional ethics codes have yet to address these issues in depth. We
      present the first empirical investigation of mental health and related
      professionals' (n = 139) attitudes and practices regarding using Internet data in
      forensic and therapeutic contexts. Respondents reported their experiences and
      levels of agreement with items measuring beliefs and attitudes toward using
      Internet-based data in various professional situations (e.g., 23% have searched
      the Internet for information about a therapy client, 39% for a forensic examinee,
      and only 26% opposed the practice for forensic evaluators). They also reported
      high levels of collective agreement, including feeling that there is a lack of
      guidance available from professional resources regarding Internet-related issues.
      Implications for forensic practice and research are presented.

PMID- 29575262
TI  - Structural basis for tumor necrosis factor blockade with the therapeutic antibody
      golimumab.
AB  - Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine, and
      elevated levels of TNFalpha in serum are associated with various autoimmune
      diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS),
      Crohn's disease (CD), psoriasis, and systemic lupus erythaematosus. TNFalpha
      performs its pleiotropic functions by binding to two structurally distinct
      transmembrane receptors, TNF receptor (TNFR) 1 and TNFR2. Antibody-based
      therapeutic strategies that block excessive TNFalpha signaling have been shown to
      be effective in suppressing such harmful inflammatory conditions. Golimumab
      (Simponi(r)) is an FDA-approved fully human monoclonal antibody targeting
      TNFalpha that has been widely used for the treatment of RA, AS, and CD. However,
      the structural basis underlying the inhibitory action of golimumab remains
      unclear. Here, we report the crystal structure of the Fv fragment of golimumab in
      complex with TNFalpha at a resolution of 2.73 A. The resolved structure reveals
      that golimumab binds to a distinct epitope on TNFalpha that does not overlap with
      the binding residues of TNFR2. Golimumab exerts its inhibitory effect by
      preventing binding of TNFR1 and TNFR2 to TNFalpha by steric hindrance. Golimumab
      does not induce conformational changes in TNFalpha that could affect receptor
      binding. This mode of action is specific to golimumab among the four anti
      TNFalpha therapeutic antibodies currently approved for clinical use.

PMID- 29575263
TI  - Mohs micrographic surgery for cutaneous malignancies: A focus review of its
      indications in pediatric age groups.
AB  - Mohs micrographic surgery (MMS) is a highly specialized technique that has been
      successful in the treatment of a variety of skin tumors. The technique can be
      performed as an outpatient procedure and encompasses surgical excision and
      intraoperative assessment of tumor margins in one setting by the same physician.
      The process ensures precise margin control with maximal preservation of healthy
      tissues. Mohs micrographic surgery has been practiced worldwide, including in the
      United States, Europe (United Kingdom, Germany, Spain, Netherlands, Switzerland),
      and Australia. Although it is commonly performed in adults with greater success,
      it has been discussed less frequently in children. In this article, we describe
      several cutaneous tumors in children and the role of Mohs micrographic surgery in
      their management. A PubMed search was conducted to review the most common
      cutaneous tumors in children treated using Mohs micrographic surgery. In this
      review, we discuss indications for Mohs micrographic surgery and pertinent
      studies examining success rates in children. Mohs micrographic surgery has been
      used to treat several tumors in children and offers the advantage of high cure
      rates and tissue conservation. This report emphasizes the benefits of Mohs
      micrographic surgery in children and highlights several cutaneous tumors for
      which it has been used to treat successfully.

PMID- 29575264
TI  - Attachment and adaptation to breast cancer: The mediating role of avoidant
      emotion processes.
AB  - Attachment insecurity is associated with difficulties in adapting to cancer.
      Accumulating evidence points to the influence of avoidant emotion processes in
      this association. This study explored this pathway by examining the association
      between attachment insecurity and quality of life in women with breast cancer,
      and by exploring the mediating role of two avoidant emotion processes in this
      association. Women with breast cancer (N = 155) completed measures of attachment,
      emotional suppression, emotional awareness and quality of life. Avoidance of
      attachment was positively associated with emotional suppression (beta = .29, p <
      .01) and lack of emotional awareness (beta = .27, p < .01), and negatively
      associated with quality of life (beta = -.22, p < .05). Lack of emotional
      awareness partially mediated the relationship between attachment avoidance and
      quality of life (indirect effect beta = -.12, p = .008). Attachment anxiety was
      not associated with any variable. Attachment avoidance may hinder the process of
      adaptation to breast cancer and difficulties in identifying and describing
      emotions may be partly responsible for this influence. Access to and ability to
      benefit from social and medical supports is likely to depend on being able to
      engage with others and recognise and process emotions effectively. Research and
      clinical implications are discussed.

PMID- 29575265
TI  - RE: "Cost-effectiveness analysis of fulvestrant versus anastrozole as first-line
      treatment for hormone receptor-positive advanced breast cancer," by Ding H., et
      al.

PMID- 29575266
TI  - "Yes, I have cancer, but I'm also lonely"; tackling a common problem in cancer
      care.

PMID- 29575267
TI  - Update of the recommendations of the Italian Society of Medical Oncology on
      vaccination for seasonal influenza and pneumococcal infection in patients with
      cancer: Focus on prevention of pneumonia.

PMID- 29575268
TI  - Revitalized and synovialized allograft for intrasynovial flexor tendon
      reconstruction in an in vivo canine model.
AB  - This study was to test our hypothesis that flexor tendon reconstruction with an
      allograft revitalized with bone marrow stromal cells (BMSCs) and synovialized
      with carbodiimide derivatized autologous synovial fluid (cd-SYN) would result in
      better digit functional restoration than the conventional allograft tendon. A
      total of 32 flexor digital profundus tendons from the second and fifth digit of
      16 dogs were created a repair failure model first. Then, failed-repaired tendons
      were reconstructed with either a revitalized-synovialized allograft tendon or a
      clinical standard autograft tendon (control group). The allograft tendon was
      seeded with autologous BMSCs in multiple slits and the graft surface was coated
      with cd-SYN. A 6 weeks after tendon reconstruction, the digits were harvested and
      evaluated for digit function, adhesion status, tendon gliding resistance,
      attachment strength, cell viability, and histologic factors. The allograft group
      had significantly improved digit function compared with the control group through
      decreased work of flexion, increased digit range of motion under 2-Newton force,
      and less adhesion score (p < .05). However, the distal attachment-site strength
      and stiffness in the allograft tendon were significantly weaker than the
      autografts (p < .05). No significant difference was found for gliding resistance.
      Histologically, allograft tendons coated with allograft had smoother surfaces and
      showed tendon-to-bone and tendon-to-tendon incorporation. Viable BMSCs were found
      in the tendon slits 6 weeks after the graft. In conclusion, cellular lubricant
      based modification of allograft tendons improved digit function and reduced the
      adhesions compared with autograft for flexor tendon reconstruction. However,
      improvement of graft-to-host tendon healing is still challenging. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 29575270
TI  - The immunomodulatory role of tumor-derived extracellular vesicles in colorectal
      cancer.
AB  - Colorectal cancer (CRC) is one of the most prevalent cancers worldwide with
      rising mortality rates predicted in the coming decades. In light of this, there
      is a continued need for improvement in our understanding of CRC biology and the
      development of novel treatment options. Tumor-derived extracellular vesicles
      (tEVs) have emerged as both novel cancer biomarkers and functional mediators of
      carcinogenesis. tEVs are released by tumor cells in abundance and play an
      important role in mediating tumor cell-immune cell interactions in the tumor
      microenvironment. Furthermore, tEVs are released into the circulation in humans
      where they could also interact with circulating immune cells. This review aims to
      describe CRC-specific tEVs and what is currently known about their role in
      immunomodulation. In particular, we discuss the ability of CRC-derived tEVs to
      affect monocyte differentiation into macrophages and dendritic cells, and their
      effects on T-cell viability and activity. Finally, the potential for tEVs in the
      development of immunotherapies will be discussed.

PMID- 29575269
TI  - Reversible Adsorption of Methylene Blue as Cationic Model Cargo onto
      Polyzwitterionic Magnetic Nanoparticles.
AB  - The reversible electrostatic adsorption of the cationic dye methylene blue (MB)
      as a model compound to polydehydroalanine (PDha)-coated magnetic multicore
      nanoparticles (MCNP) is presented. The pH responsiveness of the zwitterionic
      coating material enables reversible switching of the net surface charge of the
      PDha@MCNP hybrid particles by changes in pH and thus allows reversible adsorption
      of MB at neutral pH and desorption at low pH values. The resulting hybrid
      materials can be very interesting systems in the context of water purification,
      and the reversible adsorption is studied using UV-vis spectroscopy under varying
      surrounding conditions. The particles are characterized using dynamic light
      scattering, zeta potential measurements, transmission electron microscopy, and
      thermogravimetric analysis.

PMID- 29575271
TI  - OCT image atlas of healthy skin on sun-exposed areas.
AB  - BACKGROUND: Skin cancer represents the most prevalent type of cancer in the
      United States. Excision of these lesions can leave significant scarring, and a
      delay in the diagnosis of malignant melanoma could result in metastasis or death.
      Therefore, developing technology and criteria to accurately diagnose these
      cancers is of particular importance to the medical community. While biopsy can
      lead to scarring and infections, dermoscopy and confocal microscopy offer
      noninvasive imaging methods but are also limited in their ability to determine
      tumor depth and margins. Optical coherence tomography (OCT) is a promising
      imaging method that uses near-infrared light backscattering to image structures
      underneath the surface of the skin. The purpose of this study is to provide
      examples of variations across different skin locations and to identify common
      themes that occur with aging and sun exposure, most notably thinning of the
      epidermis and loss of a distinct dermal-epidermal junction. METHODS: Optical
      coherence tomography images were taken using the VivoSight swept-source OCT.
      Images were taken from a 23-year-old man (Subject 1) and an 89-year-old man
      (Subject 2), both with Fitzpatrick Skin Type I, who did not have any prior skin
      conditions. We investigated the regions of the body that represent sun-exposed
      areas. RESULTS: Results including OCT images taken from 19 predominately sun
      exposed areas are shown in Figure 2-Figure 20. CONCLUSION: The 2 sets of images
      demonstrate the variety that exists within OCT imaging of healthy skin, and thus,
      a comprehensive understanding of the variation in normal skin imaging using OCT
      is critical to be able to distinguish and diagnose skin cancers when present.

PMID- 29575272
TI  - Going Beyond Zip Code: Can a Person's Address Help Us Improve Their Acute Care?

PMID- 29575273
TI  - Who will treat inflammatory skin diseases in the year 2020?

PMID- 29575275
TI  - Analysis-aware microscopy video compression.
AB  - This article introduces an analysis-aware microscopy video compression method
      designed for microscopy videos that are consumed by analysis algorithms rather
      than by the human visual system. We define the quality of a microscopy video
      based on the level of preservation of analysis results. We evaluated our method
      with a bead tracking analysis program. For the same error level in the analysis
      result, our method can achieve 1,000* compression on certain test microscopy
      videos. Compared with a previous technique that yields exactly the exact same
      results by analysis algorithms, our method gives more flexibility for a user to
      control the quality. A modification to the new method also provides faster
      compression speed.

PMID- 29575274
TI  - Surface Immobilization of Transition Metal Ions on Nitrogen-Doped Graphene
      Realizing High-Efficient and Selective CO2 Reduction.
AB  - Electrochemical conversion of CO2 to value-added chemicals using renewable
      electricity provides a promising way to mitigate both global warming and the
      energy crisis. Here, a facile ion-adsorption strategy is reported to construct
      highly active graphene-based catalysts for CO2 reduction to CO. The isolated
      transition metal cyclam-like moieties formed upon ion adsorption are found to
      contribute to the observed improvements. Free from the conventional harsh
      pyrolysis and acid-leaching procedures, this solution-chemistry strategy is easy
      to scale up and of general applicability, thus paving a rational avenue for the
      design of high-efficiency catalysts for CO2 reduction and beyond.

PMID- 29575276
TI  - Falsely elevated human epididymis protein 4 results and Risk of Ovarian
      Malignancy Algorithm in polymorbid women after solid organ transplantation: A
      pilot and case-control study.
AB  - BACKGROUND: Cancer prevention is essential after transplantation (Tx). The use of
      HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) is recommended as a tool for
      selective ovarian cancer screening; however, creatinine is a known confounder.
      This study assessed the reliability of HE4, CA125, and ROMA after Tx. METHODS: We
      matched a total of 202 women without gynecological malignancies and 236 men by
      age and serum creatinine. Each pair consisted of a patient after Tx (kidney,
      liver, heart, and pancreas) and a diseased but non-Tx consecutive patient. Serum
      HE4, CA125 (Roche Cobas 6000), and creatinine (enzymatic, Abbott Architect) were
      measured in all patients. RESULTS: Creatinine correlated with HE4 (women: r =
      .864, P < .0001; men: r = .848, P < .0001). Age correlated slightly with HE4 in
      women (r = .250, P < .005) and men (r = .240, P < .0005). HE4 in women after Tx
      (median of 84.8 pmol/L) was significantly higher than non-Tx women (53.7 pmol/L,
      P < .0001) in the reference range of serum creatinine. Neither HE4 nor CA125
      correlated with tacrolimus concentration, but anemia, hyperparathyroidism,
      kidney, liver, and lung diseases were possible confounders for HE4 after
      transplantation (P < .05). CONCLUSION: Human epididymis protein 4 (HE4) was
      significantly increased in women after solid organ transplantation compared to
      levels without transplants matched by age and serum creatinine. HE4 results may
      be misleading in these patients.

PMID- 29575277
TI  - Association study of functional polymorphisms of dopaminergic pathway in epilepsy
      related factors of temporal lobe epilepsy in Brazilian population.
AB  - BACKGROUND AND PURPOSE: There are few data about the role of neurotransmission
      modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This
      is the first study that aimed to analyze the dopaminergic polymorphisms in an
      etiologically homogeneous group of patients with TLE with hippocampal sclerosis.
      Selected polymorphisms were: (i) the most expressed D2-like receptors in the
      limbic system (DRD2/ANKK1 TAQ-1A, D4_VNTR and D4_rs1800955); (ii) the dopamine
      transporter (DAT) 3'-untranslated region and intron 8; and (iii) two degrading
      enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine,
      catechol-O-methyltransferase, and monoamine oxidase A. METHODS: We assessed 119
      patients with unequivocal TLE with hippocampal sclerosis and 112 healthy
      volunteers. Individuals were genotyped for the polymorphisms of the gene encoding
      dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol
      O-methyltransferase and monoamine oxidase A. We also evaluated epilepsy-related
      factors (e.g. seizure frequency, age of onset, duration and status epilepticus).
      RESULTS: There was no difference between the groups for the studied
      polymorphisms. The polymorphism DRD4_VNTR was associated with family history of
      epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P =
      0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019)
      and family history of epilepsy (P = 0.011). CONCLUSIONS: Our findings
      demonstrated that polymorphisms of the dopaminergic pathway are associated with
      significant clinical features of this form of epilepsy, such as seizure
      frequency, family history of epilepsy and status epilepticus.

PMID- 29575278
TI  - Severe postintubation tracheobronchial rupture.
AB  - Tracheal injury is a rare complication after pediatric intubation. The choice of
      treatment depends on the size of the lesion and on the underlying disease. We
      present a complex case of severe tracheal injury treated with success with
      tracheal stent positioning.

PMID- 29575279
TI  - Enantioselective Catalyst Systems from Copper(II) Triflate and BINOL-Silanediol.
AB  - Silanediol and copper catalysis are merged, for the first time, to create an
      enhanced Lewis acid catalyst system for enantioselective heterocycle
      functionalization. The promise of this silanediol and copper catalyst combination
      is demonstrated in the enantioselective addition of indoles to alkylidene
      malonates to give rise to the desirable adducts in excellent yield and high
      enantiomeric excess. From these studies, 1,1'-bi-2-naphthol (BINOL)-based
      silanediols emerge as one-of-a-kind cocatalysts. Their potential role in the
      reaction pathway is also discussed.

PMID- 29575280
TI  - Renal regeneration after acute kidney injury.
AB  - Acute kidney injury is common and associated with negative renal and patient
      outcomes. The human kidney has a real but limited regeneration capacity.
      Understanding renal regeneration may allow us to manipulate this process and thus
      develop therapeutic weapons to improve patients' outcome. In the first part of
      this paper we discuss the clinical factors associated with renal recovery:
      baseline patient particularities, acute kidney injury characteristics and the
      medical approach taken in the short and long-term. In the second part, the
      cellular and molecular mechanisms underlying renal regeneration are explored. The
      immune system seems to have an important role, first promoting inflammation and
      then tissue healing. Other players, such as cellular senescence, mitochondrial
      dysfunction, renal haemodynamics and metabolic reprogramming also have a role in
      renal regeneration. We aim to develop a short review of renal regeneration,
      offering a holistic view of this process.

PMID- 29575281
TI  - Enantioselective Synthesis of 5,5-Disubstituted Hydantoins by Bronsted Base/H
      Bond Catalyst Assisted Michael Reactions of a Design Template.
AB  - A new method for the enantioselective synthesis of 5,5-disubstituted (quaternary)
      hydantoins was developed on the basis of an organocatalytic Michael reaction
      approach involving the use of 2-benzylthio-3,5-dihydroimidazol-4-ones as key
      hydantoin surrogates. The method is general with respect to the substitution
      pattern at the hydantoin N1 (alkyl, aryl, acyl), N3 (aryl), and C5
      (linear/branched alkyl, aryl) positions and affords essentially single
      diastereomeric products with enantioselectivities higher than 95 % ee in most
      cases. Among the bifunctional Bronsted base/H-bond catalysts examined, a known
      squaramide-tertiary amine catalyst and a newly prepared squaramide-tertiary amine
      catalyst provide the highest selectivity so far with either nitroolefins or vinyl
      ketones as the acceptor components. Kinetic measurements support a first-order
      rate dependence on both reaction partners, the donor template and the Michael
      acceptor, whereas competitive 1 H NMR spectroscopy experiments reveal the high
      ability of the template for catalyst binding.

PMID- 29575282
TI  - Genetic signatures through space, time and multiple disturbances in a ubiquitous
      brooding coral.
AB  - The predominance of self-recruitment in many reef-building corals has fundamental
      and complex consequences for their genetic diversity, population persistence and
      responses to climate change. Knowledge of genetic structure over local scales
      needs to be placed within a broad spatial context, and also integrated with
      genetic monitoring through time to disentangle these consequences. Here, we
      examined patterns of genetic diversity over multiple spatio-temporal scales
      across tropical Australia in the ubiquitous brooding coral, Seriatopora hystrix.
      We also analysed complimentary environmental and demographic data to elucidate
      the seascape drivers of these patterns. Large genetic differences were detected
      between the east vs. west coasts of Australia. In northwest Australia, geographic
      differentiation dominated genetic structure over multiple scales. However, three
      sympatric lineages were detected at the largest offshore reef system (Scott
      Reef). Similar to the differences observed among putative species in eastern
      Australia, these lineages were associated with different levels of wave exposure.
      Local genetic structure within the Scott Reef system was relatively stable over
      10 years, but temporal differences were observed that reflected small but
      important genetic changes over a few generations during recovery after severe
      bleaching. These results highlight the importance of self-recruitment together
      with occasional longer distance connectivity for the persistence of a
      metapopulation across spatially and temporally variable environments. Our
      multidimensional research provides a foundation for further long-term genetic
      monitoring to inform conservation strategies and highlights that sampling scales,
      ecological effects and cryptic diversity are important considerations to develop
      realistic understanding of the evolutionary resilience of corals.

PMID- 29575283
TI  - Polyacrylonitrile-Derived Sponge-Like Micro/Macroporous Carbon for Selective CO2
      Separation.
AB  - CO2 capture under a dynamical flow situation requires adsorbents possessing
      balanced proportion of macropores as diffusion path and micropores as adsorption
      reservoir. However, the construction of interconnected micro-/macropores
      structure coupled with abundant nitrogen species into one carbon skeleton remains
      a challenge. Here, we report a new approach to prepare sponge-like carbon with a
      well-developed micro-/macroporous structure and enriched nitrogen species through
      aqueous phase polymerization of acrylonitrile in the presence of graphene oxide.
      The tension stress caused by the uniform thermal shrinkage of polyacrylonitrile
      during the pyrolysis together with the favorable flexibility of graphene oxide
      sheets are responsible for the formation of the sponge-like morphology. The
      synergistic effect of micro-/macroporous framework and rich CO2 -philic site
      enables such carbon to decrease resistance to mass transfer and show high CO2
      dynamic selectivity over N2 (454) and CH4 (11), as well as good CO2 capacity at
      298 K under low CO2 partial pressure (0.17 bar, a typical CO2 partial pressure in
      flue gas). The above attributes make this porous carbon a promising candidate for
      CO2 capture from flue gas, methane sources and other relevant applications.

PMID- 29575284
TI  - Nitrogen fertilization raises CO2 efflux from inorganic carbon: A global
      assessment.
AB  - Nitrogen (N) fertilization is an indispensable agricultural practice worldwide,
      serving the survival of half of the global population. Nitrogen transformation
      (e.g., nitrification) in soil as well as plant N uptake releases protons and
      increases soil acidification. Neutralizing this acidity in carbonate-containing
      soils (7.49 * 109  ha; ca. 54% of the global land surface area) leads to a CO2
      release corresponding to 0.21 kg C per kg of applied N. We here for the first
      time raise this problem of acidification of carbonate-containing soils and assess
      the global CO2 release from pedogenic and geogenic carbonates in the upper 1 m
      soil depth. Based on a global N-fertilization map and the distribution of soils
      containing CaCO3 , we calculated the CO2 amount released annually from the
      acidification of such soils to be 7.48 * 1012  g C/year. This level of continuous
      CO2 release will remain constant at least until soils are fertilized by N.
      Moreover, we estimated that about 273 * 1012  g CO2 -C are released annually in
      the same process of CaCO3 neutralization but involving liming of acid soils.
      These two CO2 sources correspond to 3% of global CO2 emissions by fossil fuel
      combustion or 30% of CO2 by land-use changes. Importantly, the duration of CO2
      release after land-use changes usually lasts only 1-3 decades before a new C
      equilibrium is reached in soil. In contrast, the CO2 released by CaCO3
      acidification cannot reach equilibrium, as long as N fertilizer is applied until
      it becomes completely neutralized. As the CaCO3 amounts in soils, if present, are
      nearly unlimited, their complete dissolution and CO2 release will take centuries
      or even millennia. This emphasizes the necessity of preventing soil acidification
      in N-fertilized soils as an effective strategy to inhibit millennia of CO2 efflux
      to the atmosphere. Hence, N fertilization should be strictly calculated based on
      plant-demand, and overfertilization should be avoided not only because N is a
      source of local and regional eutrophication, but also because of the continuous
      CO2 release by global acidification.

PMID- 29575285
TI  - Diquats with Robust Chirality: Facile Resolution, Synthesis of Chiral Dyes, and
      Application as Selectors in Chiral Analysis.
AB  - Diquats with extremely high racemization barriers with DeltaG?theor of 233 kJ mol
      1 at 180  degrees C are described. Reported configurational robustness is due to
      a combination of two structural features: the rigid o-xylylene tether connecting
      the nitrogen atoms and the presence of two substituents in the bay region of the
      bipyridinium scaffold. The straightforward synthesis of diquats, plus facile
      resolution and derivatization make them attractive for chiral application
      studies. This is demonstrated by: 1) synthesis of the first non-racemic diquat
      dyes with pronounced chiroptical properties, and 2) capability of diquats to
      interact stereospecifically with chiral molecules. This suggests potential for
      diquat derivatives to be used as chiral selectors in separation methods.

PMID- 29575286
TI  - Planar xanthomas secondary to post-transplantation cholangiopathy in a 16-month
      old boy.
AB  - Planar xanthomas in children represent rare dermatologic findings associated with
      abnormalities in lipid metabolism. While planar xanthomas in Alagille's syndrome
      have been well described in the literature, there have been no cases reported of
      eruptive xanthomas in pediatric liver transplant patients. Herein we report a
      case of a 16-month-old boy status post-liver transplantation who presents with
      planar xanthomas secondary to cholangiopathy. A brief review of xanthomas and the
      related literature is also provided.

PMID- 29575287
TI  - The health of working nurses: Hypertension prevalence, awareness, treatment and
      control by medication.
AB  - AIMS: To investigate hypertension awareness, prevalence and treatment in nurses.
      BACKGROUND: Nurses are the largest health workforce group, currently facing an
      ageing demographic and the risk of chronic disease such as hypertension. Little
      is known about hypertension in nurses despite the potential impact on work
      productivity. METHODS: A cross-sectional online survey was distributed to nurses
      and midwives via the professional association and nursing directors. Questions
      were taken from published longitudinal health studies for blood pressure,
      hypertension and key sociodemographic and health factors. RESULTS: The
      participants' (n = 5,041) mean age was 47.99 (SD 11.46) years. The majority knew
      their blood pressure, more so if they were female, of higher body mass index and
      aged 45-64 years, but less so if they were smokers. Hypertension prevalence
      increased with age, peaking at the oldest ages and the majority were treated
      (anti-hypertensive medication), less so if aged <55 years. Many nurses treated
      for hypertension had poor blood pressure control, were most often aged 45-54
      years and were smokers. CONCLUSIONS: Hypertension prevalence is less in nurses
      than in the general population, however, once diagnosed treatment is not
      optimized. IMPLICATIONS FOR NURSING MANAGEMENT: The potential impact of
      hypertension on older nurses' work productivity justifies work-based support for
      risk reduction behaviours.

PMID- 29575289
TI  - Women-only treatment? Epistemologies of ignorance, intersectionality and the need
      for a feminist embodiment approach.

PMID- 29575290
TI  - The influence of psychosocial factors in veteran adjustment to civilian life.
AB  - AIM: Although most veterans have a successful transition to civilian life when
      they leave the military, some struggle to cope and adjust to the demands and
      challenges of civilian life. This study explores how a variety of psychosocial
      factors influence veteran adjustment to civilian life in Scotland, UK, and which
      of these factors predict a poor adjustment. METHODS: One hundred and fifty-four
      veterans across Scotland completed a set of questionnaires that measured veteran
      adjustment difficulty, quality of life, mental health, stigma, self-stigma,
      attitude towards help-seeking, likelihood of help-seeking, experiential
      avoidance, reappraisal and suppression. RESULTS: Veteran adjustment difficulty
      and quality of life were significantly correlated to a number of psychosocial
      factors. Mental health, experiential avoidance and cognitive reappraisal were
      found to be predictors of veteran adjustment difficulty, and experiential
      avoidance and cognitive reappraisal partially mediated the relationship between
      mental health and veteran adjustment, with experiential avoidance being the
      stronger mediator. DISCUSSION: Our findings suggest that early assessment of
      experiential avoidance and cognitive reappraisal and the provision of relevant
      emotion regulation skills training could potentially reduce the veteran's need
      for more complex (and costly) psychological interventions in the future.
      Implications for veterans, as well as the services and professionals involved
      with veteran transition and health care are discussed.

PMID- 29575288
TI  - Shifting patterns of polyribosome accumulation at synapses over the course of
      hippocampal long-term potentiation.
AB  - Hippocampal long-term potentiation (LTP) is a cellular memory mechanism. For LTP
      to endure, new protein synthesis is required immediately after induction and some
      of these proteins must be delivered to specific, presumably potentiated,
      synapses. Local synthesis in dendrites could rapidly provide new proteins to
      synapses, but the spatial distribution of translation following induction of LTP
      is not known. Here, we quantified polyribosomes, the sites of local protein
      synthesis, in CA1 stratum radiatum dendrites and spines from postnatal day 15
      rats. Hippocampal slices were rapidly fixed at 5, 30, or 120 min after LTP
      induction by theta-burst stimulation (TBS). Dendrites were reconstructed through
      serial section electron microscopy from comparable regions near the TBS or
      control electrodes in the same slice, and in unstimulated hippocampus that was
      perfusion-fixed in vivo. At 5 min after induction of LTP, polyribosomes were
      elevated in dendritic shafts and spines, especially near spine bases and in spine
      heads. At 30 min, polyribosomes remained elevated only in spine bases. At 120
      min, both spine bases and spine necks had elevated polyribosomes. Polyribosomes
      accumulated in spines with larger synapses at 5 and 30 min, but not at 120 min.
      Small spines, meanwhile, proliferated dramatically by 120 min, but these largely
      lacked polyribosomes. The number of ribosomes per polyribosome is variable and
      may reflect differences in translation regulation. In dendritic spines, but not
      shafts, there were fewer ribosomes per polyribosome in the slice conditions
      relative to in vivo, but this recovered transiently in the 5 min LTP condition.
      Overall, our data show that LTP induces a rapid, transient upregulation of large
      polyribosomes in larger spines, and a persistent upregulation of small
      polyribosomes in the bases and necks of small spines. This is consistent with
      local translation supporting enlargement of potentiated synapses within minutes
      of LTP induction.

PMID- 29575291
TI  - Moving forward: Bronchiectasis and chronic suppurative lung disease in children
      and adults in the 21st century.

PMID- 29575292
TI  - Pregnancy After Heart Transplant: Not For the Faint of Heart.
AB  - Solid organ transplantation has evolved significantly in the last 50 years. When
      heart transplantation began, patient survival was scarcely past a year[1], and
      the question of pregnancy for female heart transplant patients was not a
      significant consideration. Now, since the era of cyclosporine and conventional
      triple drug therapy, is important to anticipate that women of childbearing age
      may desire to become pregnant. Since the survival post-transplant for heart
      patients is an average of 10-12 years (with some surviving 20 years), this is not
      an unreasonable notion. This article is protected by copyright. All rights
      reserved.

PMID- 29575293
TI  - Usage and impacts of the Envirofit HM-5000 cookstove.
AB  - Burning solid fuels to fulfill daily household energy needs results in chronic
      exposure to household air pollution (HAP), which is among the world's greatest
      health risks. This paper presents the results of a cross-sectional study of
      cookstove usage, fuel consumption, and indoor PM2.5 concentrations in rural and
      urban Honduran homes cooking with the Envirofit HM-5000 metal plancha stove (n =
      32) as compared to control households using baseline cooking technologies (n =
      33). Temperature-based stove usage measurements showed high HM-5000 acceptance,
      with significant displacement of the traditional cookstoves at both the urban
      (99%, P < .05) and rural study sites (75%, P < .05). However, longer-term usage
      data collected in peri-urban households showed that participants cooked on the HM
      5000 more frequently during the 3-day monitoring period than during the following
      3 weeks. Average indoor PM2.5 was 66% lower in HM-5000 households as compared to
      control households (P < .05). Lower indoor PM2.5 concentrations observed in
      participant homes as compared to control households, supported by high usage and
      traditional stove displacement, suggest the potential for the HM-5000 to yield
      health improvements in adopting Honduran households.

PMID- 29575294
TI  - How Mycobacterium tuberculosis Galactofuranosyl Transferase 2 (GlfT2) Generates
      Alternating beta-(1-6) and beta-(1-5) Linkages: A QM/MM Molecular Dynamics Study
      of the Chemical Steps.
AB  - Mycobacterium tuberculosis features a unique cell wall that protects the
      bacterium from the external environment. Disruption of the cell wall assembly is
      a promising direction for novel anti-tuberculotic drugs. A key component of the
      cell wall is galactan, a polysaccharide chain composed of galactofuranose (Galf)
      units connected by alternating beta-(1-5) and beta-(1-6) linkages. The majority
      of the galactan chain is biosynthesized by a bifunctional enzyme-galactofuranosyl
      transferase 2 (GlfT2). GlfT2 catalyzes two reactions: the formation of beta-(1-5)
      and beta-(1-6) linkages. It was suggested that the enzyme acts through a
      processive mechanism until it adds 30-35 Galf units in a single active site. We
      applied a QM/MM string method coupled with ab initio molecular dynamics
      simulations to study the two reactions catalyzed by GlfT2. We showed that both
      reactions proceed very similarly and feature similar transition-state structures.
      We also present novel information about the ring puckering behavior of the five
      membered furanose ring during the glycosyltransferase reaction and a calculated
      transition-state structure with galactose in a furanose form that may be used as
      a guide for the rational design of very specific and extremely potent inhibitors,
      that is, transition-state analogues, for GlfT2. Due to the absence of a furanose
      form of galactose in humans, transition-state-analogous inhibitors represent an
      attractive scaffold for the development of novel antibacterial drugs.

PMID- 29575295
TI  - Physical activity experiences in children post-liver transplant: Developing a
      foundation for rehabilitation interventions.
AB  - Physical Activity (PA) plays an important role in the physical and psychosocial
      health of children and is beneficial in the treatment and prevention of
      comorbidities associated with transplantation. Despite this, PA participation in
      pediatric liver transplant recipients remains low compared to healthy peers. This
      qualitative-focused mixed-methods study explored the PA experiences and parental
      perception of these experiences, including perceived facilitators and barriers to
      PA in children post-liver transplant. Eighteen participants (9 children [median
      age 10.8 years] and 9 parents) took part in semi-structured interviews and
      completed the PedsQL Multidimensional Fatigue Scale and PAQ. Most children
      reported they were physically active (PAQ median 3.08 [IQR] 2.60-3.51),
      participating in PA for its enjoyment, regardless of their level of motor
      proficiency. Levels of fatigue (median 65.28 [IQR] 56.25-90.97) were higher than
      healthy norms and impacted PA participation in some children. Children and
      parents perceived PA as central to post-transplant recovery and valued its social
      and mental health benefits; however, parents struggled with ongoing uncertainty
      and perceived physical vulnerability of their child. This study indicates the
      need for continuing PA support and education and provides valuable information
      for family-centered interventions to increase PA and improve health outcomes in
      children post-transplant.

PMID- 29575298
TI  - Hierarchical Self-Assembly Induced by Dilution-Enhanced Hydrophobic Hydration.
AB  - Hydrophobic hydration (HH) is crucial in protein chemistry. Its role in the
      organization of molecules in water, however, remains elusive and difficult to
      investigate without appropriate model systems. Metal carbonyl vesicles (MCsomes),
      assembled from hydrophobic Fp(CH2 )6 Azobenzenetrans (Fp head=(PPh3
      )(Cp)Fe(CO)(CO-); hydrocarbon tail=(CH2 )6 Azobenzenetrans ; trans:trans
      configuration) is dispersible in water via HH of the Fp heads. We examined the
      dependence of this HH on solution conditions by taking advantage of redox
      activity and fluorescence quenching ability of hydrated Fe elements. A subtle
      variation in the HH substantially varied the solution behaviour of the MCsomes
      for hierarchical structural evolutions. This scrutiny resolved a long-standing
      challenge to explicate the role of HH in self-assembly at molecular levels, an
      imperative step to understand the biological systems.

PMID- 29575296
TI  - Modifications generated by fast photochemical oxidation of proteins reflect the
      native conformations of proteins.
AB  - Hydroxyl radical footprinting (HRF) is a nonspecific protein footprinting method
      that has been increasingly used in recent years to analyze protein structure. The
      method oxidatively modifies solvent accessible sites in proteins, which changes
      upon alterations in the protein, such as ligand binding or a change in
      conformation. For HRF to provide accurate structural information, the method must
      probe the native structure of proteins. This requires careful experimental
      controls since an abundance of oxidative modifications can induce protein
      unfolding. Fast photochemical oxidation of proteins (FPOP) is a HRF method that
      generates hydroxyl radicals via photo-dissociation of hydrogen peroxide using an
      excimer laser. The addition of a radical scavenger to the FPOP reaction reduces
      the lifetime of the radical, limiting the levels of protein oxidation. A direct
      assay is needed to ensure FPOP is probing the native conformation of the protein.
      Here, we report using enzymatic activity as a direct assay to validate that FPOP
      is probing the native structure of proteins. By measuring the catalytic activity
      of lysozyme and invertase after FPOP modification, we demonstrate that FPOP does
      not induce protein unfolding.

PMID- 29575297
TI  - Sonodynamic therapy-assisted immunotherapy: A novel modality for cancer
      treatment.
AB  - Sonodynamic therapy (SDT), which is based on photodynamic therapy (PDT), is a new
      cancer treatment modality. Unlike PDT, which has poor tissue penetration,
      ultrasound can penetrate deeply into tissues and largely target tumor tissue to
      mediate the cytotoxicity of sonosensitizers. We hypothesize that, similar to PDT,
      SDT may perform effectively as a cancer vaccine. Thus, we developed a therapeutic
      strategy to explore whether SDT can eliminate primary tumors, inhibit metastases,
      and prevent tumor relapse. In the present study, we found that HiPorfin (HPD)
      induced SDT killed tumor cells, promoted calreticulin expression on the cell
      surface and elicited immune responses. Meanwhile, we observed that SDT induced
      functional antitumor vaccination and abscopal effects in H22 tumor-bearing mice.
      Furthermore, this strategy conferred an immunological memory, which could protect
      against tumor recurrence after the elimination of the initial tumor. These
      results showed important effects of SDT on immune responses.

PMID- 29575300
TI  - The costs and benefits of pollinator dependence: empirically based simulations
      predict raspberry fruit quality.
AB  - Globally, agriculture increasingly depends on pollinators to produce many seed
      and fruit crops. However, what constitutes optimal pollination service for
      pollinator-dependent crops remains unanswered. We developed a simulation model to
      identify the optimal pollination service that maximizes fruit quality in crops.
      The model depicts the pollination (i.e., autonomous self-fertilization, pollen
      deposition) and post-pollination (i.e., pollen germination, and time from
      germination to ovule fertilization) processes leading to fruit and seed set and
      allows for negative flower-pollinator interactions, specifically pistil damage.
      We parameterized and validated the model based on empirical observations of
      commercial raspberry in western Argentina. To assess the effects of pollination
      intensity for fruit production, we conducted simulations over a range of visit
      number per flower by the two primary managed pollinators worldwide, Apis
      mellifera and Bombus terrestris. Simulations identified that ~15-35 visits per
      flower by A. mellifera or ~10-20 visits by B. terrestris provide adequate
      pollination and maximize raspberry fruit quality (i.e., estimated as the
      proportion of ovules that develop into drupelets). Visits in excess of these
      optima reduce simulated fruit quality, and flowers receiving >670 honey bee
      visits or >470 bumble bee visits would produce fruits of poorer quality than
      those receiving no bee visits. The simulations generated consistent, unbiased
      predictions of fruit quality for 12 raspberry fields. This model could be adapted
      easily to other animal-pollinated crops and used to guide efficient pollinator
      management in any agro-ecosystem.

PMID- 29575299
TI  - The PLGF/c-MYC/miR-19a axis promotes metastasis and stemness in gallbladder
      cancer.
AB  - Gallbladder cancer (GBC) is the most common malignant tumor of the biliary tract
      system. Epithelial-mesenchymal transition (EMT) plays a vital role in the process
      of tumor metastasis. Mesenchymal-like cells can serve as a source of cancer stem
      cells, which can confer the EMT phenotype. Placental growth factor (PLGF) belongs
      to the vascular endothelial growth factor family and plays a vital role in
      cancer. However, the underlying molecular mechanisms about the influence of PLGF
      on EMT in GBC remain unknown. Here we show that PLGF expression levels were
      higher in GBC tissues than in normal adjacent tissues and were associated with
      poor prognosis in GBC patients. Exogenous PLGF enhanced the migration, invasion,
      and tumorsphere formation of GBC cells. Conversely, knockdown of PLGF decreased
      the aggressive phenotype of GBC cells. Mechanistically, exogenous PLGF
      upregulated microRNA-19a (miR-19a) expression through the activation of c-MYC.
      Moreover, Spearman's correlation analysis showed a positive pairwise correlation
      among PLGF, c-MYC, and miR-19a expression in GBC tissues. Taken together, these
      results suggest that PLGF promotes EMT and tumorsphere formation through inducing
      miR-19a expression by upregulating c-MYC. Thus, PLGF could be a promising
      molecular therapeutic target for GBC.

PMID- 29575301
TI  - Position-specific 13 C/12 C analysis of amino acid carboxyl groups - automated
      flow-injection analysis based on reaction with ninhydrin.
AB  - RATIONALE: The fundamental level of stable isotopic knowledge lies at specific
      atomic positions within molecules but existing methods of analysis require
      lengthy off-line preparation to reveal this information. An automated position
      specific isotope analysis (PSIA) method is presented to determine the stable
      carbon isotopic compositions of the carboxyl groups of amino acids (delta13
      CCARBOXYL values). This automation makes PSIA measurements easier and routine.
      METHODS: An existing high-performance liquid chromatography (HPLC) gas handling
      interface/stable isotope ratio mass spectrometry system was modified by the
      addition of a post-column derivatisation unit between the HPLC system and the
      interface. The post-column reaction was optimised to yield CO2 from the carboxyl
      groups of amino acids by reaction with ninhydrin. RESULTS: The methodology
      described produced delta13 CCARBOXYL values with typical standard deviations
      below +/-0.1 0/00 and consistent differences (Delta13 CCARBOXYL values) between
      amino acids over a 1-year period. First estimates are presented for the delta13
      CCARBOXYL values of a number of internationally available amino acid reference
      materials. CONCLUSIONS: The PSIA methodology described provides a further
      dimension to the stable isotopic characterisation of amino acids at a more
      detailed level than the bulk or averaged whole-molecule level. When combined with
      on-line chromatographic separation or off-line fraction collection of protein
      hydrolysates the technique will offer an automated and routine way to study
      position-specific carboxyl carbon isotope information for amino acids, enabling
      more refined isotopic studies of carbon uptake and metabolism.

PMID- 29575302
TI  - Underlying maternal and pregnancy-related conditions account for a substantial
      proportion of neonatal morbidity in late preterm infants.
AB  - AIM: We studied the impact of maternal and pregnancy-related conditions and the
      effect of gestational age itself, on the health of infants born late preterm.
      METHODS: Singletons born in gestational weeks 34 + 0 to 41 + 6 in 1995-2013 in
      the southern region of Sweden were identified from a perinatal register. We found
      14 030 infants born late preterm and 294 814 born at term. A hierarchical system
      was developed to examine the impact of pregnancy complications. The outcomes
      studied were as follows: neonatal death, central nervous system (CNS) or
      respiratory disease, infection, neonatal admission and respiratory support. Odds
      ratios (OR) and 95% confidence intervals (95% CI) were obtained using logistic
      regression analyses. RESULTS: Late preterm infants were at increased risk for all
      outcomes compared to term infants, with adjusted ORs from 13.1 (95% CI: 12.7
      13.6) for neonatal admission to 2.3 (95% CI: 1.8-2.9) for infections. Late
      preterm birth after preterm prelabour rupture of membranes was associated with an
      overall lower risk compared to late preterm births due to other causes. Exposure
      to antepartum haemorrhage or maternal diabetes increased the risk for CNS and
      respiratory morbidity. CONCLUSION: Morbidity decreased in late preterm infants
      with increasing gestational age. Underlying conditions accounted for a
      substantial part of the morbidity.

PMID- 29575304
TI  - Comparison of three commercially available placental growth factor-based tests in
      women with suspected preterm pre-eclampsia: the COMPARE study.
AB  - OBJECTIVE: To compare the performance of three placental growth factor (PlGF)
      based tests in predicting delivery within 14 days from testing in women with
      suspected preterm pre-eclampsia before 35 weeks' gestation. METHODS: This was a
      retrospective analysis of samples collected from three prospective pregnancy
      cohort studies. Participants were pregnant women with suspected preterm pre
      eclampsia recruited in tertiary maternity units in the UK and Ireland. Samples
      were analyzed simultaneously according to the manufacturers' directions. The
      tests compared were the DELFIA Xpress PlGF 1-2-3 test, the Triage PlGF test and
      the Elecsys immunoassay soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio.
      Areas under receiver-operating characteristics curves (AUCs) were compared. The
      main outcome measure was detection of a difference of 0.05 in AUC between tests
      for delivery within 14 days of testing. RESULTS: Plasma samples from 396 women
      and serum samples from 244 women were assayed. In predicting delivery within 14
      days secondary to suspected pre-eclampsia prior to 35 weeks' gestation, no
      significant differences were observed in AUCs (P = 0.795), sensitivities (P =
      0.249), positive predictive values (P = 0.765) or negative predictive values (P =
      0.920) between the three tests. The specificity of the Elecsys sFlt-1/PlGF ratio
      test was higher than that of the other two tests (P < 0.001). CONCLUSIONS: The
      tests perform similarly in their prediction of need for delivery within 14 days
      in women with suspected pre-eclampsia. The high negative predictive values
      support the role of PlGF-based tests as 'rule-out' tests for pre-eclampsia. (c)
      2018 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley &
      Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and
      Gynecology.

PMID- 29575303
TI  - A Proposed Circuit Computation in Basal Ganglia: History-Dependent Gain.
AB  - In this Scientific Perspectives we first review the recent advances in our
      understanding of the functional architecture of basal ganglia circuits. Then we
      argue that these data can best be explained by a model in which basal ganglia act
      to control the gain of movement kinematics to shape performance based on prior
      experience, which we refer to as a history-dependent gain computation. Finally,
      we discuss how insights from the history-dependent gain model might translate
      from the bench to the bedside, primarily the implications for the design of
      adaptive deep brain stimulation. Thus, we explicate the key empirical and
      conceptual support for a normative, computational model with substantial
      explanatory power for the broad role of basal ganglia circuits in health and
      disease. (c) 2018 The Authors. Movement Disorders published by Wiley Periodicals,
      Inc. on behalf of International Parkinson and Movement Disorder Society.

PMID- 29575305
TI  - Forkhead Box M1 Transcriptionally Regulates the Expression of Long Noncoding RNAs
      Snhg8 and Gm26917 to Promote Proliferation and Survival of Muscle Satellite
      Cells.
AB  - Multiple functions have been proposed for transcription factor FoxM1, including
      the regulation of cell proliferation, differentiation, senescence, apoptosis, and
      tissue homeostasis. However, the role of FoxM1 in muscle satellite cells (SCs)
      remains unclear. In the present study, we demonstrated that FoxM1 was essential
      for the proliferation and survival of SCs. Crucially, we found that long
      noncoding RNAs (lncRNAs) Snhg8 and Gm26917 significantly regulated the
      proliferation and apoptosis of SCs, respectively, and these lncRNAs were directly
      regulated by FoxM1 in SCs. Mechanistically, Snhg8 sustained SCs proliferation by
      promoting the transcription of ribosomal proteins, while Gm26917 acted as a
      competing endogenous RNA for microRNA-29b, which accelerated apoptosis of SCs. In
      mice, conditional knockout of FoxM1 in skeletal muscle resulted in decreased
      proliferation and increased apoptosis of SCs. Thus, our studies revealed a
      previously unrecognized role of FoxM1 in SCs and uncovered two lncRNAs, Snhg8 and
      Gm26917, which function as novel targets of FoxM1 in the regulation of SCs
      proliferation and survival. Stem Cells 2018;36:1097-1108.

PMID- 29575306
TI  - 6-n-propylthiouracil taste disruption and TAS2R38 nontasting form in Parkinson's
      disease.
AB  - BACKGROUND: The few studies that evaluated taste function in Parkinson's disease
      (PD) showed inconsistent results. The inherited ability to taste the bitter
      compound of 6-n-propylthiouracil has been considered to be a paradigm of general
      taste perception. 6-n-propylthiouracil taste perception is mediated by the
      TAS2R38 receptor, and reduced 6-n-propylthiouracil sensitivity has been
      associated with several diseases not typically related to taste function.
      OBJECTIVES: We evaluated the 6-n-propylthiouracil taste perception and the
      TAS2R38 gene as genetic risk factors for the development of idiopathic PD in PD
      patients and healthy controls (HC). METHODS: The 6-n-propylthiouracil taste
      perception was assessed by testing the responsiveness, and the ability to
      recognize, 6-n-propylthiouracil and sodium chloride. The participants were
      classified for 6-n-propylthiouracil taster status and genotyped for the TAS2R38
      gene. RESULTS: A significant increase in the frequency of participants classified
      as 6-n-propylthiouracil nontasters and a reduced ability to recognize bitter
      taste quality of 6-n-propylthiouracil were found in PD patients when compared
      with healthy controls. The results also showed that only 5% of PD patients had
      the homozygous genotype for the dominant tasting variant of TAS2R38, whereas most
      of them carried the recessive nontaster form and a high number had a rare
      variant. CONCLUSIONS: Our results show that 6-n-propylthiouracil taster status
      and TAS2R38 locus are associated with PD. The 6-n-propylthiouracil test may
      therefore represent a novel, simple way to identify increased vulnerability to
      PD. Moreover, the presence of the nontasting form of TAS2R38 in PD may further
      substantiate that disease-associated taste disruption may represent a risk factor
      associated with the disease. (c) 2018 International Parkinson and Movement
      Disorder Society.

PMID- 29575307
TI  - Great East Japan Earthquake: Proactive sharing of lessons learned.

PMID- 29575309
TI  - Erratum.

PMID- 29575308
TI  - Neutropenia, hypogammaglobulinemia, and pneumonia: A case of WHIM syndrome.

PMID- 29575310
TI  - Severe form of neuroblastoma amplified sequence deficiency in an infant with
      recurrent acute liver failure.

PMID- 29575311
TI  - Bubble trouble: Cutaneous mastocytosis mistaken as non-accidental injury.

PMID- 29575312
TI  - Lung ultrasound reclassification of chest X-ray data after pediatric cardiac
      surgery.
AB  - INTRODUCTION: Lung ultrasound is gaining consensus for the diagnosis of some
      pulmonary conditions. Pulmonary complications are common in pediatric cardiac
      surgery. However, its use remains limited in this setting. Our aim was to test
      the feasibility of lung ultrasound following pediatric cardiac surgery and to
      compare lung ultrasound and chest X-ray findings, assessing whether lung
      ultrasound may provide additional information. METHODS: One hundred and thirty
      eight lung ultrasound examinations were performed in 79 children (median age 9.3
      months) at different time points after surgery. For each hemithorax, 3 areas
      (anterior/lateral/posterior) have been evaluated in the upper and lower halves of
      the chest (for a total of 6 scanning sites per side). Pleural effusion,
      atelectasis, and the number of B-lines were investigated. RESULTS: Lung
      ultrasound was feasible in all cases in at least 1 of the 3 areas. Feasibility
      was different for the lateral, posterior, and anterior areas (100%, 90%, and 78%,
      respectively). The posterior areas were more sensitive than anterior and lateral
      ones in the diagnosis of effusion/atelectasis. In 81 cases, lung ultrasound
      allowed reclassification of chest X-ray findings, including 40 new diagnoses
      (diagnosis of effusion/atelectasis with negative chest X-ray reports) and 41
      changes in diagnosis (effusions reclassified as atelectasis/severe congestion or
      vice versa). Although new diagnosis of small-to-moderate effusion/atelectasis was
      of limited clinical value, in 29 cases the new diagnosis changed the therapeutic
      approach. CONCLUSION: Lung ultrasound is feasible and accurate for the diagnosis
      of common pulmonary conditions after pediatric cardiac surgery, allowing
      reclassification of chest X-ray findings in a significant number of patients.

PMID- 29575313
TI  - Catalytic Hydrodefluorination of C-F Bonds by an Air-Stable PIII Lewis Acid.
AB  - Catalytic hydrodefluorination (HDF) of unactivated fluoroalkanes or CF3 
      substituted aryl species is performed using the PIII Lewis acids, [(bipy)PPh]2+
      (12+ ) and [(terpy)PPh]2+ (22+ ) under mild conditions (25 or 50  degrees C).
      Mechanistic studies indicate that activation of C-F bond by the PIII center is
      key. Particularly noteworthy is that the catalyst 2[B(C6 F5 )4 ]2 is air-stable
      and readily accessible from bench-stable, commercially available reagents in one
      step and can be used without isolation.

PMID- 29575314
TI  - 3 D Porous CoS2 Hexadecahedron Derived from MOC toward Ultrafast and Long
      Lifespan Lithium Storage.
AB  - A new hexadecahedron assembled by core-shell CoS2 particles@N-doped carbon (CoS2
      @NCH) is prepared successfully through the self-templating method. The CoS2 @NCH
      hybrid electrode delivers a high lithium-storage capacity of 778 mA h g-1 after
      1000 cycles at a high current density of 1 A g-1 , which is the longest cycle
      lifespan among the reported CoS2 anode materials in lithium-ion batteries.
      Furthermore, the CoS2 @NCH hybrid electrode shows excellent rate capability with
      a discharge capacity of 220 mA h g-1 at an extremely high current density of 20 A
      g-1 , and a charge capacity of 649 mA h g-1 is restored upon returning the
      current density back to 2 A g-1 . The superior performance is attributed to the
      unique construction of CoS2 @NCH. The N-doped interconnected porous carbon shells
      form highly conductive skeletons for quick electron transfer and prevent the
      electrode from collapsing. Moreover, the porous characteristic of the materials
      plays a key role: as some effective channels, the mesopores on the porous carbon
      shells provide greater access for lithium, and the mesopores derived from the
      particle interspace enables the complete immersion of the electrodes in
      electrolyte, which alleviates the volume expansion and ensures the integrity of
      the electrode. In addition, the nanosized CoS2 particles, which shorten the ion
      transport path and provide extra electroactive sites, also improve the reaction
      kinetics.

PMID- 29575315
TI  - Candida utilis fungaemia following endoscopic intervention on ureteral stent in a
      kidney transplant recipient: Case report and a review of the literature.
AB  - Infection due to species other than Candida albicans is increasing among solid
      organ transplant recipients. Candida utilis, commonly used in the food industry,
      is considered as a low-virulence yeast. We report the first case of C. utilis
      fungaemia involving a solid organ transplant recipient. The infection was
      triggered by the withdrawal of a ureteral stent and was successfully treated with
      intravenous micafungin. We also propose a review of all reported cases of
      infection caused by C. utilis.

PMID- 29575316
TI  - Toxicological effects of Camellia sinensis (green tea): A review.
AB  - Many scientific articles proved that green tea (GT), Camellia sinensis, has a
      great potential to manage central nervous system, cardiovascular, and metabolic
      diseases and treat cancer and inflammatory disorders. However, it is important to
      consider that "natural" is not always "safe." Some relevant articles reported
      side effects of GT, detrimental effects on health. The aim of this study is to
      provide a classified report about the toxicity of GT and its main constituents in
      acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the
      cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental
      toxicity of GT and its main constituents. The most important side effects have
      been reported hepatotoxicity and gastrointestinal disorders specially while
      consumed on an empty stomach. GT and its main components are not major teratogen,
      mutagen, or carcinogen substances. However, there is limited data in using them
      during pregnancy, and they should be used with caution in pregnancy, breast
      feeding, and susceptible people. Because GT and its main components have a wide
      variety of drug interactions, consideration should be taken in coadministration
      of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective
      cytotoxicity on cancerous cells that could engage them as an adjuvant substance
      in cancer therapy.

PMID- 29575317
TI  - Measuring Spin Relaxation Rates Using Satellite Exchange NMR Spectroscopy.
AB  - An approach to the indirect measurement of nuclear spin relaxation rates of low
      magnetogyric ratio (gamma) nuclei using the process of satellite exchange is
      described. The method does not require the observation of, or even the ability to
      provide radio-frequency pulses to, the low-gamma nucleus, but requires this to be
      scalar coupled to an NMR observable nucleus, such as 31 P or 1 H, making it
      especially attractive for the study of diamagnetic transition metals. In
      situations where spin relaxation is dominated by chemical shift anisotropy (CSA),
      the determination of the longitudinal spin relaxation time constant (T1 ) of the
      metal becomes possible, as illustrated for 195 Pt and 107/109 Ag.

PMID- 29575318
TI  - c-Src inhibitor selectively inhibits triple-negative breast cancer overexpressed
      Vimentin in vitro and in vivo.
AB  - Oncogene c-Src has been found to be a potential target for the treatment of
      triple-negative breast cancer (TNBC). However, the therapeutic effects of the c
      Src inhibitor on TNBC patients are controversial compared to those on cell lines.
      The molecular mechanisms of the inhibitory effects of the c-Src inhibitor on TNBC
      remain unclear. Herein, we showed that a specific c-Src inhibitor, PP2, was
      effective in inhibiting phosphorylation of c-Src in 4 cell lines: T-47D, SK-BR-3,
      SUM1315MO2, and MDA-MB-231, regardless of hormone receptors and human epidermal
      growth factor receptor 2 (HER2) expression levels. Giving PP2 preferentially
      reduced the S phase of cell cycles and inhibited colony formation in SUM1315MO2
      and MDA-MB-231, but not in SK-BR-3 and T-47D cells. Furthermore, PP2 effectively
      blocked cell migration/invasion and epithelial-mesenchymal transition (EMT) in
      TNBC cell lines, SUM1315MO2 and MDA-MB-231. An EMT biomarker, vimentin, was
      highly expressed in 2 TNBC cell lines when they were compared with SK-BR-3 and T
      47D cells. Further depletion of vimentin by shRNA remarkably attenuated the
      inhibitory effects of the c-Src inhibitor on TNBC cells in vitro and in vivo,
      indicating a crucial action of vimentin to affect the function of c-Src in TNBC.
      This study provides an important rationale for the clinic to precisely select
      TNBC patients who would benefit from c-Src inhibitor treatment. This finding
      suggests that traditional markers for TNBC are not sufficient to precisely define
      this aggressive type of cancer. Vimentin is identified as an important biomarker
      to enable categorization of TNBC.

PMID- 29575319
TI  - WHO's Service Availability and Readiness Assessment of primary health care
      services of commune health centers in a rural district of Northern Vietnam.
AB  - The objective of this study was to assess the availability and readiness of the
      primary health care (PHC) services of commune health centers (CHCs) in Quoc Oai,
      a rural district of Northern Vietnam based on the World Health Organization's
      Service Availability and Readiness Assessment (SARA) tool. The study was done in
      2 steps. First, the heads of the 21 CHCs of Quoc Oai district were interviewed
      using SARA, a quantitative survey, and the responses were then validated by
      direct observations of each facility. The results showed that although the
      average number of health staffs in each CHC met the national standards (at least
      5 staffs per CHC), its allocation within each CHC was not properly met because
      some CHCs had only 2 health staffs. Several health equipment and facilities were
      not fully available in many CHCs, and although the majority of the PHC services
      were available at the CHCs, their readiness remained limited. Several significant
      correlates between the availability of health care workers and the availability
      of the facilities and the PHC services were observed, suggesting that they depend
      upon and affect one another in the health system. Using the SARA-based inventory,
      the study helps health managers and policy makers to prioritize efforts and
      allocate resources more appropriately. To be effective, attention should be given
      to how to make facilities, services, and human resources for health ready for PHC
      activities-more investment and support from the system (from higher to lower
      level) and the government.

PMID- 29575320
TI  - List of contributors for HPM 33:1.

PMID- 29575321
TI  - Editorial.

PMID- 29575322
TI  - DNA is hypomethylated in circadian manifestations of bruxism.
AB  - OBJECTIVE: The aim of this study was to compare the global DNA methylation levels
      in patients under bruxism treatment and a control group. METHODS: Subjects
      undergoing bruxism treatment were classified in awake bruxism (42 patients),
      sleep bruxism (32 patients) and both conditions (42 patients). The control group
      included 42 individuals. A colorimetric assay (MethylFlash Methylated DNA 5-mC
      Quantification Kit, Epigenetic Group Inc., NY, USA) was used to determine the
      global DNA methylation levels. RESULTS: Statistically significant differences
      were found in amounts of methylated DNA in all circadian manifestations of
      bruxism compared with a control group (sleep bruxism = 0.95% +/- 2.02%; awake
      bruxism = 0.87% +/- 2.1%; sleep and awake bruxism = 0.17% +/- 0.25%; Control =
      1.69% +/- 1.6%; Kruskal-Wallis test [p = .0001] followed by Dunn's test [p <
      .05]). CONCLUSION: Patients undergoing bruxism treatment exhibited hypomethylated
      DNA levels when compared to control group. Our results suggest that DNA
      hypomethylation might be a novel aetiologic factor in bruxism aetiology. Further
      researches must be performed exploring the role of epigenetics modifications in
      circadian manifestations of bruxism.

PMID- 29575323
TI  - Clozapine reduces nicotine self-administration, blunts reinstatement of nicotine
      seeking but increases responding for food.
AB  - People with schizophrenia display significantly higher rates of smoking than the
      general population, which may be due to an interaction between nicotine and
      antipsychotic medication. While the conventional antipsychotic drug haloperidol
      sometimes increases cigarette smoking in patients with schizophrenia, there is
      some evidence suggesting that clozapine, an atypical antipsychotic drug, may
      reduce nicotine use in these patients. However, the effects of antipsychotic
      drugs like clozapine on aspects of nicotine self-administration and reinstatement
      have not been systematically examined. In the current study, we assessed the
      effect of clozapine on nicotine self-administration under fixed ratio and
      progressive ratio schedules of reinforcement, as well as reinstatement of
      nicotine-seeking following a period of abstinence. To determine the specificity
      of its effect on nicotine reward, we also tested the effect of clozapine on
      responding for food reinforcement under fixed ratio and progressive ratio
      schedules. For comparison, we also examined the effects of haloperidol, a first
      generation antipsychotic drug, under some of the same behavioral conditions as
      clozapine. We show that clozapine inhibits nicotine self-administration and
      reinstatement of nicotine-seeking but also increases the amount of effort that
      rats will exert for food reward. In contrast, haloperidol at a wide range of
      doses attenuated responding for nicotine and food reward, suggestive of a non
      specific reduction in reinforcer efficacy. These results show the potential
      utility of clozapine as a smoking cessation treatment for patients with
      schizophrenia, in addition to its antipsychotic properties.

PMID- 29575325
TI  - Neural Stem Cell Grafts Promote Astroglia-Driven Neurorestoration in the Aged
      Parkinsonian Brain via Wnt/beta-Catenin Signaling.
AB  - During aging-one the most potent risk factors for Parkinson's disease (PD)-both
      astrocytes and microglia undergo functional changes that ultimately hamper
      homoeostasis, defense, and repair of substantia nigra pars compacta (SNpc)
      midbrain dopaminergic (mDA) neurons. We tested the possibility of rejuvenating
      the host microenvironment and boosting SNpc DA neuronal plasticity via the
      unilateral transplantation of syngeneic neural stem/progenitor cells (NSCs) in
      the SNpc of aged mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
      experimental PD. Transplanted NSCs within the aged SNpc engrafted and migrated in
      large proportions to the tegmental aqueduct mDA niche, with 30% acquiring an
      astroglial phenotype. Both graft-derived exogenous (ex-Astro) and endogenous
      astrocytes (en-Astro) expressed Wnt1. Both ex-Astro and en-Astro were key
      triggers of Wnt/beta-catenin signaling in SNpc-mDA neurons and microglia, which
      was associated with mDA neurorescue and immunomodulation. At the aqueduct-ventral
      tegmental area level, NSC grafts recapitulated a genetic Wnt1-dependent mDA
      developmental program, inciting the acquisition of a mature Nurr1+ TH+ neuronal
      phenotype. Wnt/beta-catenin signaling antagonism abolished mDA neurorestoration
      and immune modulatory effects of NSC grafts. Our work implicates an unprecedented
      therapeutic potential for somatic NSC grafts in the restoration of mDA neuronal
      function in the aged Parkinsonian brain. Stem Cells 2018;36:1179-1197.

PMID- 29575326
TI  - The CRISPR/Cas revolution reaches the RNA world: Cas13, a new Swiss Army knife
      for plant biologists.
AB  - Application of the bacterial CRISPR/Cas systems to eukaryotes is revolutionizing
      biology. Cas9 and Cas12 (previously called Cpf1) are widely used as DNA nucleases
      for inducing site-specific DNA breaks for different kinds of genome engineering
      applications, and in their mutated forms as DNA-binding proteins to modify gene
      expression. Moreover, histone modifications, as well as cytosine methylation or
      base editing, were achieved with these systems in plants. Recently, with the
      discovery of the nuclease Cas13a (previously called C2c2), molecular biologists
      have obtained a system that enables sequence-specific cleavage of single-stranded
      RNA molecules. The latest experiments with this and also the alternative Cas13b
      system demonstrate that these proteins can be used in a similar manner in
      eukaryotes for RNA manipulation as Cas9 and Cas12 for DNA manipulations. The
      first application of Cas13a for post-transcriptional regulation of gene
      expression in plants has been reported. Recent results show that the system is
      also applicable for combating viral infection in plants. As single-stranded RNA
      viruses are by far the most abundant class of viruses in plants, the application
      of this system is of special promise for crops. More interesting applications are
      imminent for plant biologists, with nuclease dead versions of Cas13 enabling the
      ability to visualize RNA molecules in vivo, as well as to edit different kinds of
      RNA molecules at specific bases by deamination or to modify them by conjugation.
      Moreover, by combining DNA- and RNA-directed systems, the most complex of changes
      in plant metabolism might be achievable.

PMID- 29575324
TI  - Cortical microstructure in young onset Alzheimer's disease using neurite
      orientation dispersion and density imaging.
AB  - Alzheimer's disease (AD) is associated with extensive alterations in grey matter
      microstructure, but our ability to quantify this in vivo is limited. Neurite
      orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI
      technique that estimates neuritic microstructure in the form of orientation
      dispersion and neurite density indices (ODI/NDI). Mean values for cortical
      thickness, ODI, and NDI were extracted from predefined regions of interest in the
      cortical grey matter of 38 patients with young onset AD and 22 healthy controls.
      Five cortical regions associated with early atrophy in AD (entorhinal cortex,
      inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus)
      and one region relatively spared from atrophy in AD (precentral gyrus) were
      investigated. ODI, NDI, and cortical thickness values were compared between
      controls and patients for each region, and their associations with MMSE score
      were assessed. NDI values of all regions were significantly lower in patients.
      Cortical thickness measurements were significantly lower in patients in regions
      associated with early atrophy in AD, but not in the precentral gyrus. Decreased
      ODI was evident in patients in the inferior and middle temporal gyri, fusiform
      gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and
      NDI persisted following adjustment for cortical thickness, as well as each other.
      There was evidence in the patient group that cortical NDI was associated with
      MMSE performance. These data suggest distinct differences in cortical NDI and ODI
      occur in AD and these metrics provide pathologically relevant information beyond
      that of cortical thinning.

PMID- 29575328
TI  - Polycarboxylate-Templated Coordination Polymers: Role of Templates for
      Superprotonic Conductivities of up to 10-1  S cm-1.
AB  - Three coordination polymers (CPs) have been synthesized based on a [Co(bpy)(H2
      O)4 ]2+ chain (bpy=4,4'-bipyridine) by a template approach. The frameworks are
      neutralized by different templated polycarboxylate anions (furan di-carboxylate
      (fdc) in Co-fdc, benzene tri-carboxylate (btc) in Co-tri and benzene tetra
      carboxylate (btec) in Co-tetra). These templates with different degrees of
      protonation and ionic carrier concentration played significant role on crystal
      packing as well as formation of well-directed H-bonded networks which made these
      CPs perform well in proton conduction (PC). The PC value reaches to 1.49*10-1  S
      cm-1 under 80  degrees C and 98 % relative humidity (R.H.) for Co-tri, which is
      the highest among CPs/MOFs/COFs and is an example of conductivity in the order of
      10-1  S cm-1 . Co-tri and Co-tetra are excellent proton conductors at mild
      temperature (40  degrees C) and 98 % R.H. (conductivities up to 2.92*10-2 and
      1.38*10-2  S cm-1 , respectively).

PMID- 29575327
TI  - Changes in the proteome of the problem weed blackgrass correlating with multiple
      herbicide resistance.
AB  - Herbicide resistance in grass weeds is now one of the greatest threats to
      sustainable cereal production in Northern Europe. Multiple-herbicide resistance
      (MHR), a poorly understood multigenic and quantitative trait, is particularly
      problematic as it provides tolerance to most classes of chemistries currently
      used for post-emergence weed control. Using a combination of transcriptomics and
      proteomics, the evolution of MHR in populations of the weed blackgrass
      (Alopecurus myosuroides) has been investigated. While over 4500 genes showed
      perturbation in their expression in MHR versus herbicide sensitive (HS) plants,
      only a small group of proteins showed >2-fold changes in abundance, with a mere
      eight proteins consistently associated with this class of resistance. Of the
      eight, orthologues of three of these proteins are also known to be associated
      with multiple drug resistance (MDR) in humans, suggesting a cross-phyla
      conservation in evolved tolerance to chemical agents. Proteomics revealed that
      MHR could be classified into three sub-types based on the association with
      resistance to herbicides with differing modes of action (MoA), being either
      global, specific to diverse chemistries acting on one MoA, or herbicide specific.
      Furthermore, the proteome of MHR plants were distinct from that of HS plants
      exposed to a range of biotic (insect feeding, plant-microbe interaction) and
      abiotic (N-limitation, osmotic, heat, herbicide safening) challenges commonly
      encountered in the field. It was concluded that MHR in blackgrass is a uniquely
      evolving trait(s), associated with changes in the proteome that are distinct from
      responses to conventional plant stresses, but sharing common features with MDR in
      humans.

PMID- 29575329
TI  - Hunting the main player enabling Chlamydomonas reinhardtii growth under
      fluctuating light.
AB  - Photosynthetic organisms have evolved numerous photoprotective mechanisms and
      alternative electron sinks/pathways to fine-tune the photosynthetic apparatus
      under dynamic environmental conditions, such as varying carbon supply or
      fluctuations in light intensity. In cyanobacteria flavodiiron proteins (FDPs)
      protect the photosynthetic apparatus from photodamage under fluctuating light
      (FL). In Arabidopsis thaliana, which does not possess FDPs, the PGR5-related
      pathway enables FL photoprotection. The direct comparison of the pgr5, pgrl1 and
      flv knockout mutants of Chlamydomonas reinhardtii grown under ambient air
      demonstrates that all three proteins contribute to the survival of cells under
      FL, but to varying extents. The FDPs are crucial in providing a rapid electron
      sink, with flv mutant lines unable to survive even mild FL conditions. In
      contrast, the PGRL1 and PGR5-related pathways operate over relatively slower and
      longer time-scales. Whilst deletion of PGR5 inhibits growth under mild FL, the
      pgrl1 mutant line is only impacted under severe FL conditions. This suggests
      distinct roles, yet a close relationship, between the function of PGR5, PGRL1 and
      FDP proteins in photoprotection.

PMID- 29575330
TI  - Clinician researcher career pathway for registered nurses and midwives: A
      proposal.
AB  - AIM: To consider clinician researcher career frameworks and propose a new
      pathway, integrating university and health service components to support research
      career progression within nursing and midwifery practice. BACKGROUND: Hospitals
      with research-active clinicians report fewer adverse events and better patient
      outcomes. Nursing clinician researcher career development is therefore an
      international priority, yet positions and expectations associated with this are
      not always well articulated, with nurses and midwives challenged to accommodate
      research and clinical careers. DESIGN: This discussion paper describes
      nurse/midwife clinician researcher career frameworks and a new pathway that
      aligns academic and nursing role descriptions. DATA SOURCES: The new framework
      was informed by a brief literature search for international framework documents,
      three Australian state-based Nurses and Midwives Awards: the Australian
      Qualifications Framework, publically available University Academic (Research)
      Award schedules and academic staff descriptions, and state health department and
      health services publications. IMPLICATIONS FOR NURSING: The implementation of
      research-based practice is a key element of nursing and midwifery roles and
      "advanced practice" position descriptions have well-defined research
      expectations. This paper considers structures to support their achievement.
      CONCLUSION: This paper provides a blueprint for clinician researcher career
      development. It elevates the research domain as an equal alongside clinical,
      managerial and educational clinical career development.

PMID- 29575331
TI  - Retrospective Case Series on the Treatment of Painful Diabetic Peripheral
      Neuropathy With Dorsal Root Ganglion Stimulation.
AB  - BACKGROUND: The dorsal root ganglion (DRG) has been identified as an important
      neural structure in the development and maintenance of chronic pain. We present a
      retrospective case series of patients with refractory painful diabetic peripheral
      neuropathy (PDPN) that underwent electrical stimulation of the DRG and report on
      changes in their overall perceived pain and complication rates. METHODS: Ten
      diabetic males (mean age 65.2 [SD 8.8] years) with painful symptoms of the lower
      limbs were enrolled and trialed with up to four quadripolar percutaneous DRG
      stimulation leads between L2 and L5 spinal levels. Patients received a fully
      implantable neurostimulation system (Abbott Laboratories, Sunnyvale, CA, USA)
      immediately or after a successful trial period (>50% reduction in pain). Overall
      perceived pain was measured by visual analogue scale (VAS) at baseline, one-week
      postimplantation and one-, three-, six-, and twelve-month follow-up (n = 5).
      RESULTS: Ten patients were included in this retrospective study. Seven of these
      subjects received permanent stimulator implants after successful externalized or
      intraoperative trials. Two of those patients subsequently required explantation,
      due to failure to capture primary pain area (n = 1) and personal reasons (n = 1).
      For the five subjects that proceeded to clinical follow-ups, baseline VAS was
      reduced by an average of 63.90% (SD 21.39; p < 0.001) postimplantation. For four
      patients with available 12-month follow-up data, mean relative reduction in
      overall perceived pain averaged 64.16% (SD 35.8; p< 0.001). CONCLUSION: Early
      findings from this small retrospective case series, suggest DRG is a safe and
      effective neuromodulation modality to improve painful symptoms in PDPN patients.
      Future prospective trials are required to further investigate the use of DRG
      stimulation for this clinical indication.

PMID- 29575332
TI  - Outcome after high-dose chemotherapy and autologous stem cell transplantation in
      patients with aggressive B-cell non-Hodgkin's lymphoma.
AB  - OBJECTIVE: For more than two decades, high-dose chemotherapy (HDT) and autologous
      blood stem cell transplantation (ABSCT) were treatment options for patients with
      aggressive B-cell non-Hodgkin's lymphoma (B-NHL). However, the ideal timing and
      the collective patient benefits are still being debated. METHOD: We
      retrospectively analyzed the data of 163 patients with B-NHL who received an HDT
      protocol followed by ABSCT between 2001 and 2007. Patients were analyzed
      according to the time point of HDT/ABSCT to compare upfront (directly after
      induction, n = 72, 44%) versus secondary transplantation (at first relapse, n =
      91, 56%). RESULTS: The overall response rate was 100% and 94% after upfront and
      secondary HDT/ABSCT, respectively. No significant differences were found for
      hematopoietic recovery and toxicity profile. The progression-free survival (PFS)
      and overall survival (OS) probability were found to be significantly higher in
      the upfront HDT/ABSCT treatment group (P = .018 and P = .004). In multivariate
      analysis, upfront HDT/ABSCT and low IPI risk score had a significant beneficial
      effect on OS (P = .031 and P = .019). CONCLUSION: HDT and ABSCT directly after
      induction chemotherapy were confirmed to be feasible with high PFS and OS rates.
      In addition, for patients with relapse after first-line therapy and consecutively
      poor prognosis, HDT/ABSCT also offers an effective treatment strategy.

PMID- 29575333
TI  - Gene expression profiles of glucose toxicity-exposed islet microvascular
      endothelial cells.
AB  - OBJECTIVE: Islet microcirculation is mainly composed by IMECs. The aim of the
      study was to investigate the differences in gene expression profiles of IMECs
      upon glucose toxicity exposure and insulin treatment. METHODS: IMECs were treated
      with 5.6 mmol L-1 glucose, 35 mmol L-1 glucose, and 35 mmol L-1 glucose plus 10-8
      mol L-1 insulin, respectively. Gene expression profiles were determined by
      microarray and verified by qPCR. GO terms and KEGG analysis were performed to
      assess the potential roles of differentially expressed genes. The interaction and
      expression tendency of differentially expressed genes were analyzed by Path-Net
      algorithm. RESULTS: Compared with glucose toxicity-exposed IMECs, 1574 mRNAs in
      control group and 2870 mRNAs in insulin-treated IMECs were identified with
      differential expression, respectively. GO and KEGG pathway analysis revealed that
      these genes conferred roles in regulation of apoptosis, proliferation, migration,
      adhesion, and metabolic process etc. Additionally, MAPK signaling pathway and
      apoptosis were the dominant nodes in Path-Net. IMECs survival and function
      pathways were significantly changed, and the expression tendency of genes from
      euglycemia and glucose toxicity exposure to insulin treatment was revealed and
      enriched in 7 patterns. CONCLUSIONS: Our study provides a microcirculatory
      framework for gene expression profiles of glucose toxicity-exposed IMECs.

PMID- 29575335
TI  - Three-dimensional Kendrick mass plots as a tool for graphical lipid
      identification.
AB  - RATIONALE: The rising field of lipidomics strongly relies on the identification
      of lipids in complex matrices. Recent technical advances regarding liquid
      chromatography (LC) and high-resolution mass spectrometry (HRMS) enable the
      mapping of the lipidome of an organism with short data acquisition times.
      However, interpretation and evaluation of resulting multidimensional datasets are
      challenging and this is still the bottleneck regarding overall analysis times.
      METHODS: A novel adaption of Kendrick mass plot analysis is presented for a rapid
      and accurate analysis of lipids in complex matrices. Separation of lipids by
      their respective head group was achieved via hydrophilic interaction liquid
      chromatography (HILIC) coupled to HRMS. The resulting LC/HRMS datasets are
      processed to a list of chromatographically separated features by applying an
      optimized MZmine 2 workflow. All features are plotted in a three-dimensional
      Kendrick mass plot, which allows a fast identification of present lipid classes,
      based on equidistant features with fitting retention times and the same Kendrick
      mass defect. Suspected lipid classes are used for exact mass database matching to
      annotate features. A second three-dimensional Kendrick mass plot of annotated
      features of a single lipid class helps to reveal potential database mismatches,
      resulting in a curated list of identified lipid species. RESULTS: The use of the
      novel adaption of the Kendrick mass plot has accelerated the identification of
      the relevant lipid species in the green alga Chlamydomonas reinhardtii. A total
      of 106 species were identified within the lipid classes: phosphatidylserine,
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol,
      monogalactosyldiacylglycerol, digalactosyldiacylglycerol, and
      sulfoquinovosyldiacylglycerol. CONCLUSIONS: This work shows how the addition of
      chromatographic information, i.e. the retention time, to a classical two
      dimensional Kendrick mass plot enables rapid and accurate analysis of LC/HRMS
      datasets, exemplified on a green alga (C. reinhardtii) sample. Three-dimensional
      Kendrick mass plots have improved lipid class identification and fast spotting of
      falsely annotated lipid species.

PMID- 29575336
TI  - Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in
      asthmatics from NHANES 2007-12.
AB  - BACKGROUND: Fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos)
      count are biomarkers for type 2 inflammation. However, they signal different
      inflammatory pathways. Simultaneously elevated, they are related to more asthma
      events in a general population and among younger asthmatics. OBJECTIVE: To
      investigate if simultaneously elevated FeNO and B-Eos relate to asthma outcomes
      and lung function among subjects with asthma at a wide age span, and how
      different cut-offs for the markers affect these relations. METHOD: FeNO, B-Eos
      and forced expiratory volume in 1 second (FEV1 ) were assessed in 1419 subjects
      with asthma, aged 6-79 years old, from the National Health and Nutrition
      Examination Survey (NHANES) 2007-12. Elevated levels were defined as FeNO >=20
      p.p.b. for children <12 years and >=25 p.p.b. for subjects >=12 years and B-Eos
      count >=300 cells/MUL. Additional analyses were performed for the cut-offs FeNO
      >35/30 and >50/35 p.p.b., and for B-Eos >=400 and >= 500 cells/MUL, as well as
      for different age subgroups (6-17, 18-44, >44 years old). Asthma events during
      the past year were self-reported. RESULTS: Subjects with simultaneously elevated
      FeNO and B-Eos compared with normal levels of both markers had a higher adjusted
      odds ratio (aOR (95%CI)) for having FEV1 <80% of predicted (2.15 (1.28-3.59),
      wheeze disturbing sleep (1.88 (1.27, 2.78)) but did not differ regarding asthma
      attacks past year. Elevated B-Eos, but not FeNO, was related to higher aOR for
      asthma attack (1.57 (1.14, 2.18) or emergency room (ER) visit due to asthma (1.88
      (1.33, 2.64) when elevated FeNO and elevated B-Eos were studied as independent
      predictors. CONCLUSION: Simultaneously elevated FeNO and B-Eos related to reduced
      lung function in asthmatics, wheezing symptoms, but not to a history of asthma
      attacks. Asthma attacks and ER-visit due to asthma were related to increased B
      Eos levels.

PMID- 29575334
TI  - Hispidulin suppresses cell growth and metastasis by targeting PIM1 through
      JAK2/STAT3 signaling in colorectal cancer.
AB  - Colorectal cancer (CRC) accounts for over 600 000 deaths annually worldwide. The
      current study aims to evaluate the value of proto-oncogene PIM1 as a therapeutic
      target in CRC and investigate the anticancer activity of hispidulin, a naturally
      occurring phenolic flavonoid compound, against CRC. Immunohistochemistry analysis
      showed that PIM1 was upregulated in CRC tissue. The role of PIM1 as an oncogene
      was evidenced by the fact that PIM1 knockdown inhibits cell growth, induces
      apoptosis, and suppresses invasion. Our results showed that hispidulin exerts
      antitumor activity in CRC through inhibiting the expression of PIM1. Moreover,
      our findings revealed that hispidulin downregulated the expression of PIM1 by
      inhibiting JAK2/STAT3 signaling by generating reactive oxygen species.
      Furthermore, our in vivo studies showed that hispidulin can significantly inhibit
      tumor growth and metastasis in CRC. Collectively, our results provide an
      experimental basis for trialing hispidulin in CRC treatment. PIM1 can be
      considered a potential therapeutic target in CRC.

PMID- 29575337
TI  - Diurnal periodicity of assimilate transport shapes resource allocation and whole
      plant carbon balance.
AB  - Whole-plant carbon balance comprises diurnal fluctuations of photosynthetic
      carbon gain and respiratory losses, as well as partitioning of assimilates
      between phototrophic and heterotrophic organs. Because it is difficult to access,
      the root system is frequently neglected in growth models, or its metabolism is
      rated based on generalizations from other organs. Here, whole-plant cuvettes were
      used for investigating total-plant carbon exchange with the environment over full
      diurnal cycles. Dynamics of primary metabolism and diurnally resolved phloem
      exudation profiles, as proxy of assimilate transport, were combined to obtain a
      full picture of resource allocation. This uncovered a strong impact of
      periodicity of inter-organ transport on the efficiency of carbon gain. While a
      sinusoidal fluctuation of the transport rate, with minor diel deflections,
      minimized respiratory losses in Arabidopsis wild-type plants, triangular or
      rectangular patterns of transport, found in mutants defective in either starch or
      sucrose metabolism, increased root respiration at the end or beginning of the
      day, respectively. Power spectral density and cross-correlation analysis revealed
      that only the rate of starch synthesis was strictly correlated to the rate of net
      photosynthesis in wild-type, while in a sucrose-phosphate synthase mutant
      (spsa1), this applied also to carboxylate synthesis, serving as an alternative
      carbon pool. In the starchless mutant of plastidial phospho-gluco mutase (pgm),
      none of these rates, but concentrations of sucrose and glucose in the root,
      followed the pattern of photosynthesis, indicating direct transduction of shoot
      sugar levels to the root. The results demonstrate that starch metabolism alone is
      insufficient to buffer diurnal fluctuations of carbon exchange.

PMID- 29575338
TI  - Polymer-Brush-Grafted Mesoporous Silica Nanoparticles for Triggered Drug
      Delivery.
AB  - Mesoporous silica nanoparticles (MSNs) have been demonstrated to be one of the
      most promising drug-delivery systems (DDSs) to transport a variety of
      drugs/biomolecules. Functionalization of MSN surfaces with responsive polymer
      brushes leads to intelligent and controllable drug-delivery properties, that is,
      the encapsulated drugs/biomolecules will only be released upon certain stimuli
      including pH, temperature, light, enzyme, ultrasound, or redox, thus maximizing
      their therapeutic efficiency and minimizing side effects. These polymer brushes
      can also increase the stability and extend the release period of the loaded
      cargoes. This Minireview presents an overview of recent research progress on
      stimuli-responsive controlled DDSs based on polymer-brush-grafted MSNs. Utilizing
      the switching abilities of the grafted responsive polymer brushes, the smart DDSs
      show great potential for biomedical applications, especially for cancer therapy.

PMID- 29575340
TI  - Soil properties and sediment accretion modulate methane fluxes from restored
      wetlands.
AB  - Wetlands are the largest source of methane (CH4 ) globally, yet our understanding
      of how process-level controls scale to ecosystem fluxes remains limited. It is
      particularly uncertain how variable soil properties influence ecosystem CH4
      emissions on annual time scales. We measured ecosystem carbon dioxide (CO2 ) and
      CH4 fluxes by eddy covariance from two wetlands recently restored on peat and
      alluvium soils within the Sacramento-San Joaquin Delta of California. Annual CH4
      fluxes from the alluvium wetland were significantly lower than the peat site for
      multiple years following restoration, but these differences were not explained by
      variation in dominant climate drivers or productivity across wetlands. Soil iron
      (Fe) concentrations were significantly higher in alluvium soils, and alluvium CH4
      fluxes were decoupled from plant processes compared with the peat site, as
      expected when Fe reduction inhibits CH4 production in the rhizosphere. Soil
      carbon content and CO2 uptake rates did not vary across wetlands and, thus, could
      also be ruled out as drivers of initial CH4 flux differences. Differences in
      wetland CH4 fluxes across soil types were transient; alluvium wetland fluxes were
      similar to peat wetland fluxes 3 years after restoration. Changing alluvium CH4
      emissions with time could not be explained by an empirical model based on
      dominant CH4 flux biophysical drivers, suggesting that other factors, not
      measured by our eddy covariance towers, were responsible for these changes.
      Recently accreted alluvium soils were less acidic and contained more reduced Fe
      compared with the pre-restoration parent soils, suggesting that CH4 emissions
      increased as conditions became more favorable to methanogenesis within wetland
      sediments. This study suggests that alluvium soil properties, likely Fe content,
      are capable of inhibiting ecosystem-scale wetland CH4 flux, but these effects
      appear to be transient without continued input of alluvium to wetland sediments.

PMID- 29575339
TI  - Treatment response and non-response in CBT and Network Support for alcohol
      disorders: targeted mechanisms and common factors.
AB  - AIMS: To determine whether mechanisms of drinking behavior change that are
      targeted by specific treatments mediate the effects of Packaged Cognitive
      Behavior Therapy (PCBT) and Network Support (NS) on abstinence rates throughout
      27 months. DESIGN: Secondary analysis of data from two Network Support Project
      randomized clinical trials, in which participants were assigned to either a case
      management control treatment (control) or NS treatment in trial 1, or to PCBT or
      NS treatment in trial 2. SETTING: An out-patient substance abuse treatment site
      at a university medical center in the United States. PARTICIPANTS: A total of 249
      men and 154 women (n = 403) with alcohol use disorder. MEASUREMENTS: The primary
      outcome was membership in a treatment responder class determined by growth
      mixture modeling (GMM) of monthly proportion days abstinent (PDA) to 27 months.
      Key predictors of responder class membership included network change variables,
      and changes in coping scores and self-efficacy. FINDINGS: GMM analyses indicated
      that a three-class solution provided the best fit to the data: a treatment
      responder class comprising almost 55% of patients, a late relapsing class that
      showed post-treatment gains followed by a return to baseline drinking (12.7% of
      patients) and a non-responder class (32% of patients). Analyses indicated that
      treatment effects on responder class membership were moderated by baseline
      drinking (P < 0.001). PCBT effects were mediated by changes in coping scores (P <
      0.05). NS treatment effects were also mediated by coping change, as well as by
      increases in self-efficacy and in number of abstinent friends (P < 0.05).
      CONCLUSIONS: Long-term success in Packaged Cognitive Behavior Therapy and Network
      Support treatments for alcohol use disorder appears to be mediated by both
      general mechanisms (developing coping skills and self-efficacy) and treatment
      targeted mechanisms (developing network strategies that emphasize social support
      and avoiding friends who drink).

PMID- 29575342
TI  - Actinic keratoses seldom occur alone.

PMID- 29575343
TI  - Predatory journals abuse the flood of publishable material.

PMID- 29575341
TI  - Coexistence of gastrointestinal stromal tumor and leiomyosarcoma of the stomach
      presenting as a collision tumor: A case report and review of literature.
AB  - Collision tumor of the stomach is rare. We report a rare case of a gastric
      collision tumor consisting of gastrointestinal stromal tumors (GISTs) and
      leiomyosarcoma (LMS). Computed tomography scan revealed a 15 cm sized mass in the
      posterior wall of the body of the stomach. Gross examination of the wedge
      resection specimen showed the tumor located in the muscularis propria with
      extramural protrusion into the peritoneal cavity and the gastric cavity with
      geographic necrosis, hemorrhage, and mucosal ulceration. Histologically, the
      majority of the tumor consisted of the GIST component and the minor area in the
      submucosal region consisted of the LMS component. The tumor showed an abrupt
      transition between GIST and LMS by histologically and immunohistochemically,
      suggesting a collision tumor. Furthermore, the GIST components exhibited a c-kit
      exon 11 mutation. On the other hand, LMS component exhibited neither c-kit nor
      platelet-derived growth factor receptor-alpha (PDGFRA) mutation. Here we describe
      a case of the collision tumor consisting of GIST and LMS and its literature
      review.

PMID- 29575344
TI  - Laser- and RF-based treatments for acne vulgaris: new interesting options a
      commentary.

PMID- 29575346
TI  - The association between gait and physical fitness in adults with intellectual
      disabilities.
AB  - BACKGROUND: Gait deviations are often seen in adults with intellectual
      disabilities (ID). Their low physical fitness levels may be associated with these
      deviations. Understanding the impact of fitness on gait in this population is
      important for developing interventions to improve gait. In a cross-sectional
      study, we assessed the association between multiple physical fitness components
      and spatiotemporal gait parameters in adults with ID. METHOD: Gait
      characteristics of 31 adults (42.77 +/- 16.70 years) with ID without Down
      syndrome were assessed with the GAITRite at comfortable (CS) and fast speed (FS),
      along with fitness assessments (body composition, muscular endurance, strength,
      balance, Short Physical Performance Battery). RESULTS: At CS, adults with ID with
      higher BMI and/or waist circumference spent more time in double support. At FS,
      those with better muscular endurance took steps faster, those with better balance
      took bigger steps and strides and those with better Short Physical Performance
      Battery scores took bigger steps and strides at higher velocity. CONCLUSIONS:
      Body composition was mostly associated with gait at CS, while the other physical
      fitness components were mostly associated with gait at FS. Better fitness may
      therefore be more important in more challenging conditions. These insights are
      useful for developing interventions to improve gait in adults with ID.

PMID- 29575345
TI  - Risk factors for multidrug-resistant Gram-negative bacteria infection in
      intensive care units: A meta-analysis.
AB  - AIMS: To identify the risk factors for multidrug-resistant Gram-negative bacteria
      systematically and provide suggestions and an evidence-base for clinical
      measures. BACKGROUND: With the increase in the social population, changes in
      human behaviour and ecosystems, as well as economic development, bacteria have
      gradually produced drug resistance genes. These have swept through intensive care
      units causing high mortality. METHODS: Relevant literature which included case
      control and cohort studies published from January 1999 to March 2017 were
      searched in the Cochrane Library, PubMed, Web of Science, and Medline. Meta
      analysis was performed by using StataSE version 12.0 software. RESULTS: Eighteen
      studies of 235 publications were eligible. Male gender (OR 1.40, 95%CI 1.09,
      1.80), having an operative procedure (OR 1.31, 95%CI 1.10, 1.56), a central
      venous catheter (OR 1.22, 95%CI 1.01, 1.48), mechanical ventilation (OR 1.25,
      95%CI 1.07, 1.46), previous antibiotic therapy (OR 1.66, 95%CI 1.41, 1.96),
      length of ICU stay (weighted mean difference 8.18, 95%CI 0.27, 16.10), and types
      of health-associated infections were the identified risk factors for multidrug
      resistant Gram-negative bacterial infection in intensive care units; moreover,
      diabetes mellitus was not. CONCLUSION: Six risk factors were associated with
      multidrug-resistant Gram-negative bacterial infection in intensive care units.
      Antimicrobial stewardship, infection control, and medical staff prevention care
      are needed.

PMID- 29575347
TI  - Predictive power of food web models based on body size decreases with trophic
      complexity.
AB  - Food web models parameterised using body size show promise to predict trophic
      interaction strengths (IS) and abundance dynamics. However, this remains to be
      rigorously tested in food webs beyond simple trophic modules, where indirect and
      intraguild interactions could be important and driven by traits other than body
      size. We systematically varied predator body size, guild composition and richness
      in microcosm insect webs and compared experimental outcomes with predictions of
      IS from models with allometrically scaled parameters. Body size was a strong
      predictor of IS in simple modules (r2  = 0.92), but with increasing complexity
      the predictive power decreased, with model IS being consistently overestimated.
      We quantify the strength of observed trophic interaction modifications, partition
      this into density-mediated vs. behaviour-mediated indirect effects and show that
      model shortcomings in predicting IS is related to the size of behaviour-mediated
      effects. Our findings encourage development of dynamical food web models
      explicitly including and exploring indirect mechanisms.

PMID- 29575349
TI  - Rapid divergence of mussel populations despite incomplete barriers to dispersal.
AB  - Striking genetic structure among marine populations at small spatial scales is
      becoming evident with extensive molecular studies. Such observations suggest
      isolation at small scales may play an important role in forming patterns of
      genetic diversity within species. Isolation-by-distance, isolation-by-environment
      and historical priority effects are umbrella terms for a suite of processes that
      underlie genetic structure, but their relative importance at different spatial
      and temporal scales remains elusive. Here, we use marine lakes in Indonesia to
      assess genetic structure and assess the relative roles of the processes in
      shaping genetic differentiation in populations of a bivalve mussel (Brachidontes
      sp.). Marine lakes are landlocked waterbodies of similar age (6,000-10,000
      years), but with heterogeneous environments and varying degrees of connection to
      the sea. Using a population genomic approach (double-digest restriction-site
      associated DNA sequencing), we show strong genetic structuring across populations
      (range FST : 0.07-0.24) and find limited gene flow through admixture plots. At
      large spatial scales (>1,400 km), a clear isolation-by-distance pattern was
      detected. At smaller spatial scales (<200 km), this pattern is maintained, but
      accompanied by an association of genetic divergence with degree of connection. We
      hypothesize that (incomplete) dispersal barriers can cause initial isolation,
      allowing priority effects to give the numerical advantage necessary to initiate
      strong genetic structure. Priority effects may be strengthened by local
      adaptation, which the data may corroborate by showing a high correlation between
      mussel genotypes and temperature. Our study indicates an often-neglected role of
      (evolution-mediated) priority effects in shaping population divergence.

PMID- 29575350
TI  - Regulatory T cells in autoimmune skin diseases.
AB  - CD4+ Foxp3+ regulatory T cells (Tregs) are suppressors of immune activation and
      play a crucial role in the maintenance of peripheral tolerance. Mutations of
      Foxp3 result in fatal autoimmunity in multiple organs, including the skin, in
      both humans and mice. Many studies have demonstrated the altered frequency and
      functions of Tregs, changes in cytokine and chemokine levels related to Tregs and
      the differences in genetic background regarding Tregs in autoimmune skin
      disorders. Recent studies have extended our knowledge of certain properties of
      Tregs, especially skin-resident Tregs. In addition, some novel therapies have
      been performed by modulating the number and the function of Tregs. This review
      focuses on the role of Tregs in some autoimmune skin disorders, including
      alopecia areata, vitiligo, pemphigoid and pemphigus, and systemic sclerosis, and
      discusses questions that remain to be addressed.

PMID- 29575348
TI  - The tempo of human childhood: a maternal foot on the accelerator, a paternal foot
      on the brake.
AB  - Relative to the life history of other great apes, that of humans is characterized
      by early weaning and short interbirth intervals (IBIs). We propose that in modern
      humans, birth until adrenarche, or the rise in adrenal androgens, developmentally
      corresponds to the period from birth until weaning in great apes and ancestral
      hominins. According to this hypothesis, humans achieved short IBIs by subdividing
      ancestral infancy into a nurseling phase, during which offspring fed at the
      breast, and a weanling phase, during which offspring fed specially prepared
      foods. Imprinted genes influence the timing of human weaning and adrenarche, with
      paternally expressed genes promoting delays in childhood maturation and
      maternally expressed genes promoting accelerated maturation. These observations
      suggest that the tempo of human development has been shaped by consequences for
      the fitness of kin, with faster development increasing maternal fitness at a cost
      to child fitness. The effects of imprinted genes suggest that the duration of the
      juvenile period (adrenarche until puberty) has also been shaped by evolutionary
      conflicts within the family.

PMID- 29575351
TI  - Measuring the impact of pharmacoepidemiologic research using altmetrics: A case
      study of a CNODES drug-safety article.
AB  - PURPOSE: To provide an overview of altmetrics, including their potential benefits
      and limitations, how they may be obtained, and their role in assessing
      pharmacoepidemiologic research impact. METHODS: Our review was informed by
      compiling relevant literature identified through searching multiple health
      research databases (PubMed, Embase, and CIHNAHL) and grey literature sources
      (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in
      particular, may use altmetrics to understand scholarly impact and knowledge
      translation by providing a case study of a drug-safety study conducted by the
      Canadian Network of Observational Drug Effect Studies. RESULTS: A common approach
      to measuring research impact is the use of citation-based metrics, such as an
      article's citation count or a journal's impact factor. "Alternative" metrics, or
      altmetrics, are increasingly supported as a complementary measure of research
      uptake in the age of social media. Altmetrics are nontraditional indicators that
      capture a diverse set of traceable, online research-related artifacts including
      peer-reviewed publications and other research outputs (software, datasets, blogs,
      videos, posters, policy documents, presentations, social media posts, wiki
      entries, etc). CONCLUSION: Compared with traditional citation-based metrics,
      altmetrics take a more holistic view of research impact, attempting to capture
      the activity and engagement of both scholarly and nonscholarly communities.
      Despite the limited theoretical underpinnings, possible commercial influence,
      potential for gaming and manipulation, and numerous data quality-related issues,
      altmetrics are promising as a supplement to more traditional citation-based
      metrics because they can ingest and process a larger set of data points related
      to the flow and reach of scholarly communication from an expanded pool of
      stakeholders. Unlike citation-based metrics, altmetrics are not inherently rooted
      in the research publication process, which includes peer review; it is unclear to
      what extent they should be used for research evaluation.

PMID- 29575352
TI  - Heart rate variability characteristics of patients with irritable bowel syndrome
      and associations with symptoms.
AB  - BACKGROUND: Disturbed brain-gut interactions are assumed to be of importance for
      symptom generation in patients with irritable bowel syndrome (IBS). The autonomic
      nervous system (ANS) is part of the bidirectional brain-gut communication, but
      previous studies in IBS show diverging results. We aimed to identify subgroups of
      IBS patients with distinct ANS characteristics differentiating them from healthy
      controls (HC), and to study associations between ANS status and symptoms.
      METHODS: Heart rate variability (HRV) was measured in IBS patients and HC (Holter
      monitoring: supine and standing positions with controlled respiration and
      ambulatory 24-hour period). Frequency (5 minutes, supine, standing) and time
      domains (24 hours, day, night) were analyzed. Validated questionnaires were used
      to measure gastrointestinal and psychological symptoms in patients. Patients and
      HC were compared on a univariate and multivariate level (principal component
      analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS
      DA)). KEY RESULTS: We analyzed 158 IBS patients (Rome III) and 39 HC. Patients
      differed significantly from HC in HRV parameters during daytime and in standing
      position. In the PCA, a majority of patients overlapped with HC, but the weighted
      means differed (P < .01). A subset of patients (n = 30; 19%) with an aberrant
      global HRV profile was identified through PCA and OPLS-DA; these patients
      reported more severe symptoms of frequent (P < .05) and loose stools (P = .03),
      as well as urgency (P = .01). CONCLUSIONS AND INFERENCES: Altered ANS function
      was demonstrated in patients with IBS, and this might be of particular relevance
      for symptoms in a subset of the patients.

PMID- 29575353
TI  - Scale and direction of adaptive introgression between black cottonwood (Populus
      trichocarpa) and balsam poplar (P. balsamifera).
AB  - Introgression can introduce novel genetic variation at a faster rate than
      mutation alone and result in adaptive introgression when adaptive alleles are
      maintained in the recipient genome over time by natural selection. A previous
      study from our group demonstrated adaptive introgression from Populus balsamifera
      into P. trichocarpa in a target genomic region. Here we expand our local ancestry
      analysis to the whole genome of both parents to provide a comprehensive view of
      introgression patterns and to identify additional candidate regions for adaptive
      introgression genomewide. Populus trichocarpa is a large, fast-growing tree of
      mild coastal regions of the Pacific Northwest, whereas P. balsamifera is a
      smaller stature tree of continental and boreal regions with intense winter cold.
      The species hybridize where they are parapatric. We detected asymmetric patterns
      of introgression across the whole genome of these two poplar species adapted to
      contrasting environments, with stronger introgression from P. balsamifera to P.
      trichocarpa than vice versa. Admixed P. trichocarpa individuals contained more
      genomic regions with unusually high levels of introgression (19 regions) and also
      the largest introgressed genome fragment (1.02 Mb) compared with admixed P.
      balsamifera (nine regions). Our analysis also revealed numerous candidate regions
      for adaptive introgression with strong signals of selection, notably related to
      disease resistance, and enriched for genes that may play crucial roles in
      survival and adaptation. Furthermore, we detected a potential overrepresentation
      of subtelomeric regions in P. balsamifera introgressed into P. trichocarpa and
      possible protection of sex-determining regions from interspecific gene flow.

PMID- 29575354
TI  - Prolonged T-wave peak-end interval in Down syndrome patients with congenitally
      normal hearts.
AB  - BACKGROUND: Heterogeneity of ventricular repolarization has been assessed using
      the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts.
      Novel repolarization indexes, that is, T-wave peak-end (Tp-e) interval and Tp
      e/QT ratio, however, have not previously been evaluated in these patients. The
      aim of this study was therefore to evaluate the Tp-e interval and Tp-e/QT ratio
      in DS patients without congenital heart defects. METHODS: Tp-e interval, Tp-e
      dispersion, and Tp-e/QT ratio were compared between 160 DS patients and 110 age-
      and sex-matched healthy controls on 12-lead surface electrocardiogram. RESULTS:
      Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were
      significantly higher in the DS group than the control group. CONCLUSION:
      Myocardial repolarization indexes in DS patients with congenitally normal hearts
      were found to be prolonged compared with those in normal controls. Further
      evaluation is warranted to elucidate the relationship between prolonged
      repolarization indexes and arrhythmic events in these patients.

PMID- 29575355
TI  - Family aggregation of language impairment in an isolated Chilean population from
      Robinson Crusoe Island.
AB  - BACKGROUND: It has been reported that the inhabitants of the Chilean Robinson
      Crusoe Island have an increased frequency of specific language impairment (SLI)
      or developmental language disorder (DLD). AIMS: To explore the familial
      aggregation of DLD in this community. METHODS & PROCEDURES: We assessed the
      frequency of DLD amongst colonial children between the ages of 3 and 8;11 years
      (50 individuals from 45 nuclear families). Familial aggregation rates of language
      disorder were calculated by assessing all available first-degree relatives (n =
      107, 77 parents, 25 siblings, five half-siblings) of the probands. OUTCOMES &
      RESULTS: We found that 71% of the child population performed significantly below
      expected in measures of phonological production or expressive and receptive
      morphology. The majority of these children presented with severe expressive
      and/or receptive language difficulties. One-quarter of language-disordered
      probands primarily had phonological difficulties. Family members of affected
      probands experienced a higher risk of language disorder than those of typically
      developing probands. This increased risk was apparent regardless of non-verbal
      IQ. CONCLUSIONS & IMPLICATIONS: The study substantiates the existence of a
      familial form of speech and language disorder on Robinson Crusoe Island.
      Furthermore, we find that the familiarity is stable regardless of non-verbal IQ,
      supporting the recent movement to reduce the importance of non-verbal IQ
      criterion in DLD diagnoses.

PMID- 29575356
TI  - Emerging threat of the 21st century lightscape to global biodiversity.
AB  - Over the last century the temporal and spatial distribution of light on Earth has
      been drastically altered by human activity. Despite mounting evidence of
      detrimental effects of light pollution on organisms and their trophic
      interactions, the extent to which light pollution threatens biodiversity on a
      global scale remains unclear. We assessed the spatial extent and magnitude of
      light encroachment by measuring change in the extent of light using satellite
      imagery from 1992 to 2012 relative to species richness for terrestrial and
      freshwater mammals, birds, reptiles, and amphibians. The encroachment of light
      into previously dark areas was consistently high, often doubling, in areas of
      high species richness for all four groups. This pattern persisted for nocturnal
      groups (e.g., bats, owls, and geckos) and species considered vulnerable to
      extinction. Areas with high species richness and large increases in light extent
      were clustered within newly industrialized regions where expansion of light is
      likely to continue unabated unless we act to conserve remaining darkness.
      Implementing change at a global scale requires global public, and therefore
      scientific, support. Here, we offer substantial evidence that light extent is
      increasing where biodiversity is high, representing an emerging threat to global
      biodiversity requiring immediate attention.

PMID- 29575357
TI  - RASopathic comedo-like or cystic lesions induced by Vemurafenib: A model of skin
      lesions similar but not identical to those induced by dioxins (MADISH).
AB  - BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often
      develop skin lesions similar to those observed after exposure to dioxin-like
      compounds. We previously called these lesions MADISH (metabolizing acquired
      dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning.
      OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions
      observed under vemurafenib treatment with MADISH in order to bring to light a
      possible cross-talk between vemurafenib and dioxin pathways. METHODS: In this
      case-series study we explored the histological aspect of skin lesions in 10 cases
      treated with vemurafenib for malignant melanoma. We also analysed the ability of
      vemurafenib and tyrosine kinase inhibitors to induce dioxin-AhR pathway. RESULTS:
      All patients had skin lesions diagnosed as "non-inflammatory acneiform eruption"
      by dermatologists. These were predominantly facial with notable retro-auricular
      involvement and clinically compatible with chloracne/MADISH when assessed by
      dioxin expert. Histological analysis showed mostly comedo-like lesions and dermal
      cysts containing epithelial wall with basal or lateral epithelial projections and
      lamellar keratinization, and alterations of remaining sebaceous glands. The
      expression of CYP1A1, a gene highly induced following dioxin exposure, was not
      observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors
      erlotinib and gefitinib did not induce CYP1A1 activity. DISCUSSION: Although the
      skin lesions under vemurafenib treatment were morphologically similar to MADISH,
      the absence of CYP1A1 expression in dermal cysts of patients and the absence of
      CYP1A1 activation by vemurafenib led us consider that these skin lesions were
      different from true MADISH and not mediated by a cross-talk of AhR signalling,
      but rather to a hyperactivation of PI3K-Akt pathway as a consequence of
      vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of
      dermal cysts must be required, parallel to the morphology of the lesions, to make
      the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen
      compounds. This article is protected by copyright. All rights reserved.

PMID- 29575358
TI  - ProtaBank: A repository for protein design and engineering data.
AB  - We present ProtaBank, a repository for storing, querying, analyzing, and sharing
      protein design and engineering data in an actively maintained and updated
      database. ProtaBank provides a format to describe and compare all types of
      protein mutational data, spanning a wide range of properties and techniques. It
      features a user-friendly web interface and programming layer that streamlines
      data deposition and allows for batch input and queries. The database schema
      design incorporates a standard format for reporting protein sequences and
      experimental data that facilitates comparison of results across different data
      sets. A suite of analysis and visualization tools are provided to facilitate
      discovery, to guide future designs, and to benchmark and train new predictive
      tools and algorithms. ProtaBank will provide a valuable resource to the protein
      engineering community by storing and safeguarding newly generated data, allowing
      for fast searching and identification of relevant data from the existing
      literature, and exploring correlations between disparate data sets. ProtaBank
      invites researchers to contribute data to the database to make it accessible for
      search and analysis. ProtaBank is available at https://protabank.org.

PMID- 29575359
TI  - A retrospective histopathological, immunohistochemical and molecular study of the
      presence of Leishmania spp. in the skin of cats with head and neck ulcerative
      dermatitis.
AB  - BACKGROUND: Head and neck ulcers in cats can arise from allergic and nonallergic
      disorders, including feline leishmaniosis (FeL). It is important to rule out this
      aetiological agent in regions that are endemic for canine leishmaniosis, because
      the drugs used to treat immune-mediated disorders of cats can be contraindicated
      in the setting of infection. HYPOTHESIS/OBJECTIVES: The aim of this study was to
      evaluate the skin of cats with ulcerative dermatitis of the head or neck for
      evidence of Leishmania infection using combined immunohistochemistry (IHC) and
      Polymerase Chain Reaction (PCR). An IHC for tissue histiocytes was also utilized
      because leishmaniosis may provoke a histiocytic inflammatory response. ANIMALS:
      Twenty seven cats with head and/or neck ulcers. METHODS: Skin biopsy specimens
      were examined for the presence of Leishmania spp. by routine histopathological
      evaluation and IHC using a polyclonal anti-Leishmania antibody, and by
      quantitative PCR (qPCR). The ionized calcium-binding adapter molecule-1 (IBA-1)
      antibody was used to immunolocalize histiocytes. Selected history and clinical
      data were recorded. RESULTS: All specimens showed a superficial mid-perivascular
      mixed inflammatory infiltrate. The presence of histiocytes was confirmed in 23 of
      27 cases with the IBA-1 antibody. Immunohistochemistry and qPCR techniques
      confirmed the absence of Leishmania in all cases. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Leishmania did not seem to play a role in the pathogenesis of feline
      ulcerative dermatitis of the head and neck in the subjects studied, despite a
      lifestyle potentially associated with infection. Histiocytic infiltration of
      tissue is not a specific marker for Leishmania infection in this population.

PMID- 29575360
TI  - Effects of fenoldopam on kidney function parameters and its therapeutic efficacy
      in the management of acute kidney injury in dogs with heatstroke.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in dogs, but evidence of efficacy
      of its treatment is lacking. OBJECTIVE: To evaluate the efficacy of fenoldopam in
      the management of AKI. ANIMALS: Forty dogs with naturally occurring heatstroke.
      METHODS: Dogs were prospectively enrolled and divided into treatment and the
      placebo groups (fenoldopam, constant rate infusion [CRI] of 0.1 ug/kg/min or
      saline, respectively). Urine production (UP) was measured using a closed system.
      Urinary clearances were performed at 4, 12, and 24 hours after presentation to
      estimate the effect of fenoldopam on UP, glomerular filtration rate (GFR) and
      sodium fractional excretion (NaFE). RESULTS: At presentation, severity of
      heatstroke, based on a previously developed scoring system, was similar between
      the study groups, but was significantly worse in nonsurvivors compared with
      survivors. Fenoldopam administration was not associated with hypotension. Overt
      AKI was diagnosed, based on the International Renal Interest Society guidelines
      in 22/40 (55%) of the dogs. Overall, 14/40 dogs (35%) died, with no significant
      (P = .507) mortality rate difference between the fenoldopam (6/20 dogs; 30%) and
      placebo (8/20; 40%) groups. The proportion of dogs with AKI did not differ
      between the fenoldopam and the placebo groups (9/20; 45% versus 13/20; 65%,
      respectively; P = .204). There were no differences in UP, GFR, and NaFE between
      the fenoldopam and the placebo groups. CONCLUSION AND CLINICAL IMPORTANCE:
      Fenoldopam CRI at 0.1 ug/kg/min did not have a clinically relevant effect on
      kidney function parameters in dogs with severe heatstroke-associated AKI.

PMID- 29575361
TI  - Effects of alkaloids from Sophora flavescens on osteoblasts infected with
      Staphylococcus aureus and osteoclasts.
AB  - Chronic osteomyelitis is primarily caused by infection with Staphylococcus aureus
      (S. aureus). Antibiotics are commonly administered; however, it is a challenge to
      promote bone healing. The aim of this study was to investigate the in vitro
      effects of alkaloids from the herbal remedy Sophora flavescens (ASF) on rat
      calvarial osteoblasts (ROBs) infected with S. aureus and healthy osteoclasts.
      Cell proliferation and alkaline phosphatase, interleukin-6, and tumour necrosis
      factor-alpha activity was measured in infected ROBs; tartrate-resistant acid
      phosphatase was evaluated in osteoclasts via enzyme-linked immunosorbent assay.
      The mRNA and protein expression levels of bone morphogenetic protein 2, runt
      related transcription factor 2, osteoprotegerin, and receptor activator of
      nuclear factor kappa-B ligand were assessed in infected ROBs through reverse
      transcription-polymerase chain reaction and western blotting analysis,
      respectively. Results indicated that ASF increased the viability of uninfected
      ROBs and infected ROBs treated with vancomycin via regulation of bone
      morphogenetic protein 2, runt-related transcription factor, osteoprotegerin, and
      receptor activator of nuclear factor kappa-B ligand mRNA and protein expression
      levels. In addition, the secretion of the inflammatory factor tumour necrosis
      factor-alpha was decreased and alkaline phosphatase activity was increased,
      inhibiting the viability of osteoclasts and tartrate-resistant acid phosphatase
      activity. Therefore, the herbal remedy ASF has potential as a new treatment for
      chronic osteomyelitis.

PMID- 29575362
TI  - IgLON5 antibodies are infrequent in patients with isolated sleep apnea.

PMID- 29575364
TI  - Unilateral pain and shorter duration of chronic migraine are significant
      predictors of response to onabotulinumtoxin A.

PMID- 29575365
TI  - Smoking is a cause of ischaemic stroke, not a risk factor!

PMID- 29575366
TI  - Mitonuclear discordance in wolf spiders: Genomic evidence for species integrity
      and introgression.
AB  - Systematists and taxonomists have benefited greatly from the emergence of
      molecular methods. Species identification has become straightforward through DNA
      barcoding and the rapid build-up of massive DNA barcode reference libraries. In
      animals, mitonuclear discordance can significantly complicate the process of
      species identification and delimitation. The causes of mitonuclear discordance
      are either biological (e.g., introgression, incomplete lineage sorting,
      horizontal gene transfer androgenesis) or induced by operational factors (e.g.,
      human error with specimen misidentification or incorrect species delimitation).
      Moreover, endosymbionts may play an important role in promoting fixation of
      mitochondrial genomes. Here, we study the mitonuclear discordance of wolf spiders
      species (Lycosidae) (independent cases from Alopecosa aculeata and Pardosa
      pullata groups) that share identical COI DNA barcodes. We approached the case
      utilizing double-digest restriction site-associated DNA sequencing (ddRADseq) to
      obtain and analyse genomic-scale data. Our results suggest that the observed
      cases of mitonuclear discordance are not due to operational reasons but result
      from biological processes. Further analysis indicated introgression and that
      incomplete lineage sorting is unlikely to have been responsible for the observed
      discrepancy. Additional survey of endosymbionts provided ideas on further
      research and their role in shaping mitochondrial DNA distribution patterns. Thus,
      ddRADseq grants an efficient way to study the taxonomy of problematic groups with
      insight into underlying evolutionary processes.

PMID- 29575367
TI  - Transition-Metal-Like Behavior of Monovalent Boron Compounds: Reduction,
      Migration, and Complete Cleavage of CO at a Boron Center.
AB  - The borylene-carbonyl moiety in [bis(silylene)B(CO)][WBr(CO)5 ] shows diverse
      reactivity. Reduction, migration, and complete cleavage of CO have been observed
      at the boron center, leading to the formation of new types of borylenes. These
      reactions not only serve as new methods for the synthesis of various stable
      borylenes, but also demonstrate that main-group-element compounds can mimic the
      behavior of transition-metal complexes.

PMID- 29575369
TI  - Drink Less Enjoy More: effects of a multi-component intervention on improving
      adherence to, and knowledge of, alcohol legislation in a UK nightlife setting.
AB  - AIMS: To estimate the association between implementation of a community-based
      multi-component intervention (Drink Less Enjoy More) and sales of alcohol to
      pseudo-intoxicated patrons and nightlife patron awareness of associated
      legislation. DESIGN: Cross-sectional pre-intervention and follow-up measurements,
      including alcohol test purchases (using pseudo-intoxicated patrons) in licensed
      premises (stratified random sample; 2013, 2015) and a survey with nightlife
      patrons (convenience sample; 2014, 2015). SETTING: One UK municipality with a
      large night-time economy. PARTICIPANTS: Licensed premises (pre = 73; follow-up =
      100); nightlife patrons (pre = 214; follow-up = 202). INTERVENTION: The Drink
      Less Enjoy More intervention included three interacting components: community
      mobilization and awareness-raising; responsible bar server training; and active
      law enforcement of existing legislation prohibiting sales of alcohol to, and
      purchasing of alcohol for, a person who appears to be alcohol intoxicated:
      'intoxicated', herein for economy. MEASUREMENTS: The primary outcomes were
      alcohol service refusal to pseudo-intoxicated patrons and nightlife patron
      knowledge of alcohol legislation (illegal to sell alcohol to, and purchase
      alcohol for, intoxicated people), adjusted for potential confounders including
      characteristics of the area, venue, test purchase and nightlife patron. FINDINGS:
      Pre-intervention, 16.4% of alcohol sales were refused, compared with 74.0% at
      follow-up (P < 0.001). In adjusted analyses, the odds of service refusal were
      higher at follow-up [adjusted odds ratio (aOR) = 14.63, P < 0.001]. Service
      refusal was also associated with server gender and patron drunkenness within the
      venue. Among drinkers, accurate awareness of alcohol legislation was higher at
      follow-up (sales: pre = 44.5%; follow-up = 66.0%; P < 0.001/purchase: pre =
      32.5%; follow-up = 56.0%; P < 0.001). In adjusted analyses, knowledge of
      legislation was higher at follow-up (sales: aOR = 2.73, P < 0.001; purchasing:
      aOR = 2.73, P < 0.001). Knowledge of legislation was also associated with
      participant age (purchasing) and expectations of intoxication (sales).
      CONCLUSION: A community-based multi-component intervention concerning alcohol
      sales legislation in the United Kingdom (UK) was associated with a reduction in
      sales of alcohol to pseudo-intoxicated patrons in on-licensed premises in a UK
      nightlife setting and an improvement in nightlife patron awareness of associated
      legislation.

PMID- 29575368
TI  - MicroRNA-708-3p mediates metastasis and chemoresistance through inhibition of
      epithelial-to-mesenchymal transition in breast cancer.
AB  - Metastasis and chemoresistance remain major challenges in the clinical treatment
      of breast cancer. Recent studies show that dysregulated microRNAs (miRNAs) play
      an important role in metastasis and chemoresistance development in breast cancer.
      Herein, we identified downregulated expression of miR-708-3p in breast cancers.
      In particular, miR-708-3p expression was significantly decreased in specimens
      from breast cancer patients with metastasis compared to that in specimens from
      patients with no metastasis. Consistent with clinical data, our in vitro data
      show that miR-708-3p was more significantly decreased in invasive breast cancer
      cell lines. In addition, our data show that inhibition of miR-708-3p
      significantly stimulated breast cancer cell metastasis and induced
      chemoresistance both in vitro and in vivo. In contrast, overexpression of miR-708
      3p dramatically inhibited breast cancer cell metastasis and enhanced the
      sensitivity of breast cancer cells to chemotherapy both in vitro and in vivo.
      Furthermore, we identified that miR-708-3p inhibits breast cancer cell epithelial
      to-mesenchymal transition (EMT) by directly targeting EMT activators, including
      ZEB1, CDH2 and vimentin. Taken together, our findings suggest that miR-708-3p
      acts as a cancer suppressor miRNA and carries out its anticancer function by
      inhibiting EMT in breast cancer. In addition, our findings suggest that
      restoration of miR-708-3p may be a novel strategy for inhibiting breast cancer
      metastasis and overcoming the chemoresistance of breast cancer cells.

PMID- 29575370
TI  - Atomic Iridium Incorporated in Cobalt Hydroxide for Efficient Oxygen Evolution
      Catalysis in Neutral Electrolyte.
AB  - Developing highly efficient catalysts for oxygen evolution reaction (OER) in
      neutral media is extremely crucial for microbial electrolysis cells and
      electrochemical CO2 reduction. Herein, a facile one-step approach is developed to
      synthesize a new type of well-dispersed iridium (Ir) incorporated cobalt-based
      hydroxide nanosheets (nominated as CoIr) for OER. The Ir species as clusters and
      single atoms are incorporated into the defect-rich hydroxide nanosheets through
      the formation of rich Co-Ir species, as revealed by systematic synchrotron
      radiation based X-ray spectroscopic characterizations combining with high-angle
      annular dark-field scanning transmission electron microscopy measurement. The
      optimized CoIr with 9.7 wt% Ir content displays highly efficient OER catalytic
      performance with an overpotential of 373 mV to achieve the current density of 10
      mA cm-2 in 1.0 m phosphate buffer solution, significantly outperforming the
      commercial IrO2 catalysts. Further characterizations toward the catalyst after
      undergoing OER process indicate that unique Co oxyhydroxide and high valence Ir
      species with low-coordination structure are formed due to the high oxidation
      potentials, which authentically contributes to superior OER performance. This
      work not only provides a state-of-the-art OER catalyst in neutral media but also
      unravels the root of the excellent performance based on efficient structural
      identifications.

PMID- 29575371
TI  - Practical guide to dynamic pelvic floor MRI.
AB  - : Pelvic floor dysfunction encompasses a spectrum of functional disorders that
      result from impairment of the ligaments, fasciae, and muscles supporting the
      pelvic organs. It is a prevalent disorder that carries a lifetime risk over 10%
      for undergoing a surgical repair. Pelvic floor weakness presents as a wide range
      of symptoms, including pain, pelvic pressure or bulging, urinary and fecal
      incontinence, constipation, and sexual dysfunction. A correct diagnosis by
      clinical examination alone can be challenging, particularly in cases involving
      multiple compartments. Magnetic resonance imaging (MRI) allows noninvasive,
      radiation-free, high soft-tissue resolution evaluation of all three pelvic
      compartments, and has proved a reliable technique for accurate diagnosis of
      pelvic floor dysfunction. MR defecography with steady-state sequences allows
      detailed anatomic and functional evaluation of the pelvic floor. This article
      provides an overview of normal anatomy and function of the pelvic floor and
      discusses a practical approach to the evaluation of imaging findings of pelvic
      floor relaxation, pelvic organ prolapse, fecal incontinence, and obstructed
      defecation. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018;47:1155-1170.

PMID- 29575372
TI  - Radar plots: A novel modality for displaying disparate data on the efficacy of
      eluxadoline for the treatment of irritable bowel syndrome with diarrhea.
AB  - BACKGROUND: Patients with irritable bowel syndrome with diarrhea (IBS-D)
      experience a range of abdominal and bowel symptoms; successful management
      requires alleviation of this constellation of symptoms. Eluxadoline, a locally
      active mixed MU- and kappa-opioid receptor agonist and delta-opioid receptor
      antagonist, is approved for the treatment of IBS-D in adults based on the results
      of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation
      of diverse but interrelated efficacy endpoints. METHODS: Two double-blind,
      placebo-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomized patients
      meeting Rome III criteria for IBS-D to twice-daily eluxadoline 75 or 100 mg or
      placebo. Radar plots were prepared showing pooled Weeks 1-26 response rates for
      the primary efficacy composite endpoint (simultaneous improvement in abdominal
      pain and stool consistency), stool consistency, abdominal pain, urgency-free
      days, and adequate relief, and change from baseline to Week 26 in IBS-D global
      symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and
      daily number of bowel movements. KEY RESULTS: The studies enrolled 2428 patients.
      Eluxadoline increased Weeks 1-26 responder proportions vs placebo for the
      composite endpoint, stool consistency, abdominal pain, urgency-free days, and
      adequate relief. Changes from baseline to Week 26 in IBS-D global symptom score,
      abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel
      movements were greater with eluxadoline vs placebo. CONCLUSIONS AND INFERENCES:
      Data presentation in radar plot format facilitates interpretation across multiple
      domains, demonstrating that eluxadoline treatment led to improvements vs placebo
      across 13 endpoints representing the range of symptoms experienced by patients
      with IBS-D.

PMID- 29575374
TI  - Gene therapy clinical trials worldwide to 2017: An update.
AB  - To date, almost 2600 gene therapy clinical trials have been completed, are
      ongoing or have been approved worldwide. Our database brings together global
      information on gene therapy clinical activity from trial databases, official
      agency sources, published literature, conference presentations and posters kindly
      provided to us by individual investigators or trial sponsors. This review
      presents our analysis of clinical trials that, to the best of our knowledge, have
      been or are being performed worldwide. As of our November 2017 update, we have
      entries on 2597 trials undertaken in 38 countries. We have analysed the
      geographical distribution of trials, the disease indications (or other reasons)
      for trials, the proportions to which different vector types are used, and the
      genes that have been transferred. Details of the analyses presented, and our
      searchable database are available via The Journal of Gene Medicine Gene Therapy
      Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We
      also provide an overview of the progress being made in gene therapy clinical
      trials around the world, and discuss key trends since the previous review, namely
      the use of chimeric antigen receptor T cells for the treatment of cancer and
      advancements in genome editing technologies, which have the potential to
      transform the field moving forward.

PMID- 29575373
TI  - The anatomical components of the cardiac outflow tract of chondrichthyans and
      actinopterygians.
AB  - The outflow tract of the fish heart is the segment interposed between the
      ventricle and the ventral aorta. It holds the valves that prevent blood backflow
      from the gill vasculature to the ventricle. The anatomical composition,
      histological structure and evolutionary changes in the fish cardiac outflow tract
      have been under discussion for nearly two centuries and are still subject to
      debate. This paper offers a brief historical review of the main conceptions about
      the cardiac outflow tract components of chondrichthyans (cartilaginous fish) and
      actinopterygians (ray-finned fish) which have been put forward since the
      beginning of the nineteenth century up to the current day. We focus on the
      evolutionary origin of the outflow tract components and the changes to which they
      have been subject in the major extant groups of chondrichthyans and
      actinopterygians. In addition, an attempt is made to infer the primitive
      anatomical design of the heart of the gnathostomes (jawed vertebrates). Finally,
      several areas of further investigation are suggested. Recent work on fish heart
      morphology has shown that the cardiac outflow tract of chondrichthyans does not
      consist exclusively of the myocardial conus arteriosus as classically thought. A
      conus arteriosus and a bulbus arteriosus, devoid of myocardium and mainly
      composed of elastin and smooth muscle, are usually present in cartilaginous and
      ray-finned fish. This is consistent with the suggestion that both components
      coexisted from the onset of the gnathostome radiation. There is evidence that the
      conus arteriosus appeared in the agnathans. By contrast, the evolutionary origin
      of the bulbus is still unclear. It is almost certain that in all fish, both the
      conus and bulbus develop from the embryonic second heart field. We suggest herein
      that the primitive anatomical heart of the jawed vertebrates consisted of a sinus
      venosus containing the pacemaker tissue, an atrium possessing trabeculated
      myocardium, an atrioventricular region with compact myocardium which supported
      the atrioventricular valves, a ventricle composed of mixed myocardium, and an
      outflow tract consisting of a conus arteriosus, with compact myocardium in its
      wall and valves at its luminal side, and a non-myocardial bulbus arteriosus that
      connected the conus with the ventral aorta. Chondrichthyans have retained this
      basic anatomical design of the heart. In actinopterygians, the heart has been
      subject to notable changes during evolution. Among them, the following two should
      be highlighted: (i) a decrease in size of the conus in combination with a
      remarkable development of the bulbus, especially in teleosts; and (ii) loss of
      the myocardial compact layer of the ventricle in many teleost species.

PMID- 29575375
TI  - A re-examination of the BIS/BAS scales: Evidence for BIS and BAS as
      unidimensional scales.
AB  - OBJECTIVES: Carver and White's behavioral inhibition system and behavioral
      activation system (BIS/BAS) scales are the most widely used to assess constructs
      of the revised reinforcement sensitivity theory. This study provides a re
      examination of the latent structure of the original BIS/BAS scales. METHODS: The
      interpretability of the three purported BAS subfactors relative to a "general
      behavioral activation" factor was assessed using Schmid-Leiman and standard
      confirmatory factor analysis. Regarding the BIS scale, comparisons were made
      between (a) Carver and White's unidimensional BIS model, (b) Johnson, Turner, and
      Iwata's 2-factor BIS model, (c) Heym, Ferguson, and Lawrence's alternative 2
      factor BIS model, and (d) a modified Heym et al. model (unidimensional)
      controlling for method effects of reverse-scored items. RESULTS: Results revealed
      the majority of variance of individual BAS items was accounted for by a common,
      general BAS dimension. Additionally, for the BIS scale, results of the chi2
      difference statistical test supporting the 1-factor model, as well as the noted
      theoretical and psychometric difficulties in interpreting a multifactor BIS
      scale, provide converging support that BIS items actually represent a single,
      unidimensional factor. CONCLUSIONS: The collective results suggested that the BIS
      and BAS scales should be conceptualized as separate unidimensional measures,
      which is consistent with theory behind the original development.

PMID- 29575376
TI  - Incomplete Hippocampal Inversion and Its Relationship to Hippocampal Subfield
      Volumes and Aging.
AB  - BACKGROUND AND PURPOSE: Incomplete hippocampal inversion (IHI) is an atypical
      anatomical pattern presented by the hippocampus. It is associated with several
      neuropathological conditions and is thought to be a factor of susceptibility to
      hippocampal sclerosis and loss of volume. The volume loss of hippocampus is an
      inevitable consequence of aging, and when accelerated it is commonly considered
      an imaging biomarker of Alzheimer's disease dementia. METHODS: We have studied
      the relationship between IHI and hippocampal subfield volumes in a cohort of 60
      healthy participants of 49-87 years of age. The presence and severity of IHI and
      hippocampal subfield volumes were quantified from T2 magnetic resonance (MR)
      images acquired at 3T. RESULTS: It was found that IHI presented in 23.3% of
      participants. Right unilateral IHI was rare (two cases, 3.3%) in comparison to
      left unilateral IHI (nine cases, 15%), with three (5%) of participants showing
      bilateral IHI. No significant relationships between the whole hippocampal volumes
      and IHI were observed. Instead, significant relationships between the volumes of
      the left and right cornu ammonis subfield-1 (CA1) and IHI scores were evident.
      CONCLUSIONS: The rates of IHI prevalence in the current cohort are similar to
      those previously reported in healthy cohorts. The IHI severity is related to
      hippocampal subfield volumes, most notably the CA1, which is a novel finding with
      potential implications in research on aging and dementia.

PMID- 29575377
TI  - Site-Selective Cysteine-Cyclooctyne Conjugation.
AB  - We report a site-selective cysteine-cyclooctyne conjugation reaction between a
      seven-residue peptide tag (DBCO-tag, Leu-Cys-Tyr-Pro-Trp-Val-Tyr) at the N or C
      terminus of a peptide or protein and various aza-dibenzocyclooctyne (DBCO)
      reagents. Compared to a cysteine peptide control, the DBCO-tag increases the rate
      of the thiol-yne reaction 220-fold, thereby enabling selective conjugation of
      DBCO-tag to DBCO-linked fluorescent probes, affinity tags, and cytotoxic drug
      molecules. Fusion of DBCO-tag with the protein of interest enables regioselective
      cysteine modification on proteins that contain multiple endogenous cysteines;
      these examples include green fluorescent protein and the antibody trastuzumab.
      This study demonstrates that short peptide tags can aid in accelerating bond
      forming reactions that are often slow to non-existent in water.

PMID- 29575378
TI  - Recent use of medical infrared thermography in skin neoplasms.
AB  - BACKGROUND: Infrared thermal imaging captures the infrared radiation emitted by
      the skin surface. The thermograms contain valuable information, since the
      temperature distribution can be used to characterize physiological anomalies.
      Thus, the use of infrared thermal imaging (IRT) has been studied as a possible
      medical tool to aid in the diagnosis of skin oncological lesions. The aim of this
      review is to assess the current state of the applications of IRT in skin neoplasm
      identification and characterization. METHODS: A literature survey was conducted
      using the reference bibliographic databases: Scopus, PubMed and ISI Web of
      Science. Keywords (thermography, infrared imaging, thermal imaging and skin
      cancer) were combined and its presence was verified at the title and abstract of
      the article or as a main topic. Only articles published after 2013 were
      considered during this search. RESULTS: In total, 55 articles were encountered,
      resulting in 14 publications for revision after applying the exclusion criteria.
      It was denoted that IRT have been used to characterize and distinguish between
      malignant and benign neoplasms and different skin cancer types. IRT has also been
      successfully applied in the treatment evaluation of these types of lesions.
      CONCLUSION: Trends and future challenges have been established to improve the
      application of IRT in this field, disclosing that dynamic thermography is a
      promising tool for early identification of oncological skin conditions.

PMID- 29575380
TI  - Polyelectrolyte-Graphene Oxide Multilayer Composites for Array of Microchambers
      which are Mechanically Robust and Responsive to NIR Light.
AB  - Development of composite polymer/graphene oxide (GO) materials attracts
      significant attention due to their unique properties. In this work, highly
      ordered arrays of hollow microchambers made of composite polyelectrolyte/GO
      multilayers (PEGOMs) are successfully fabricated via layer-by-layer assembly on
      sacrificial or sustainable templates having imprinted patterns of microwells on
      their surface. Mechanical and optical properties of PEGOMs are studied by
      nanoindentation and near-infrared (NIR) absorption spectroscopy. Incorporation of
      three GO layers in between the polyelectrolyte multilayer stacks increases
      Young's modulus and critical stress of the microchambers by a factor of 5.6 and
      2.6, respectively. Optical density of this PEGOM film is found to decrease
      gradually from 0.14 at lambda = 800 nm to 0.06 at lambda = 1500 nm. Remote
      opening of PEGOM microchambers with NIR laser beam is also demonstrated. One of
      the possible applications of the developed structures includes micropackaging and
      delivery systems in biological tissues with remote triggering.

PMID- 29575379
TI  - Identification of ectopic ovotestis in a dog with XX ovotesticular, SRY-negative,
      disorder of sexual development.
AB  - A 1-year-old, previously spayed phenotypic female Poodle/Soft-coated Wheaten
      Terrier (Whoodle) cross was presented for a suspected ovarian remnant. Serum
      luteinizing hormone (LH) concentration was below the detection limit (<1 ng/ml
      Witness(r) LH), and serum progesterone concentration was elevated in the
      chemiluminescence immunoassay (CLIA; 20 ng/ml), consistent with dioestrus and
      presence of ovarian tissue. Transabdominal ultrasound revealed a retroperitoneal
      soft tissue structure suspected to be a gonad. On exploratory laparotomy, a gonad
      was removed from the cranial retroperitoneum, cranial to the right kidney, after
      ligation of its primary blood supply. Histological examination proved the gonad
      to be an ovotestis. Subsequent cytogenetics revealed a 78 XX karyotype, thus
      confirming the diagnosis of ectopic ovotestis in a XX ovotesticular, SRY
      negative, disorder of sexual development in a dog.

PMID- 29575381
TI  - Comprehension and face validity of the Exercise Adherence Rating Scale in
      patients with persistent musculoskeletal pain.

PMID- 29575382
TI  - Between older adults' needs and the law: The Israeli Long Term Care Insurance Law
      from the Perspectives of Service Users and Providers.
AB  - The Israeli Long Term Care Insurance Law (LTCIL) was one of the first long term
      care insurances in the world to support older adults and their family members and
      allow them to stay in their homes for as long as possible. The present study
      aimed to evaluate the perspectives of older adults, their family members and home
      care workers regarding the LTCIL. Views of workers of the National Insurance
      Institute (NII), which is directly responsible for the enactment of the law, are
      also integrated. Interviews were conducted between June 2016 and June 2017.
      Thematic qualitative analysis is based on interviews with 15 NII workers, 31
      older adults, 31 family members, and 6 paid home care workers. The present study
      stresses the tension between the LTCIL and older adults' perceived rights and
      needs. It also demonstrates how even though the NII workers are engaged with
      various stakeholders, they often lack direct contact with older adults, their
      family members and paid home care workers: those most directly influenced by the
      LTCIL. Policy considerations are discussed.

PMID- 29575383
TI  - Phaeohyphomycosis due to Pleurostomophora richardsiae: an uncommon cutaneous
      fungal infection.

PMID- 29575385
TI  - Transcranial Sonography to Differentiate Primary Intracerebral Hemorrhage from
      Cerebral Infarction with Hemorrhagic Transformation.
AB  - BACKGROUND AND PURPOSE: The differentiation of primary intracerebral hemorrhage
      (ICH) from parenchymal hemorrhagic transformation within an ischemic infarction
      (PHI) is crucial in order to adapt therapeutic measures. We hypothesized that a
      distinction of ICH and PHI can be made at bedside via transcranial gray-scale and
      perfusion sonography. METHODS: We prospectively included 14 patients with
      intracranial hemorrhage on admission imaging in this pilot study. Differentiation
      between ICH and PHI was made either by cerebral magnetic resonance imaging or
      follow-up computed tomography scan. All patients were examined via gray-scale and
      perfusion sonography. RESULTS: Eight patients were diagnosed with ICH, and 6
      patients with PHI. Volumes of ICH did not differ between the two groups. However,
      PHI patients showed a significantly larger perfusion deficit compared to ICH
      patients (P < .01). At a cutoff value of 1.41 of the mismatch index of perfusion
      deficit and hyperechogenic lesion, the PHI diagnosis can be made with a 100%
      sensitivity and 100%-specificity. CONCLUSION: Differentiation of ICH and PHI via
      multimodal transcranial sonography with mismatch imaging is possible. Since
      sonographic imaging as a bedside-method is cost- as well as time-efficient, it
      may be a helpful tool for differentiation between these two entities particularly
      in critically ill patients with unclear ICH.

PMID- 29575384
TI  - Drivers of vegetative dormancy across herbaceous perennial plant species.
AB  - Vegetative dormancy, that is the temporary absence of aboveground growth for >= 1
      year, is paradoxical, because plants cannot photosynthesise or flower during
      dormant periods. We test ecological and evolutionary hypotheses for its
      widespread persistence. We show that dormancy has evolved numerous times. Most
      species displaying dormancy exhibit life-history costs of sprouting, and of
      dormancy. Short-lived and mycoheterotrophic species have higher proportions of
      dormant plants than long-lived species and species with other nutritional modes.
      Foliage loss is associated with higher future dormancy levels, suggesting that
      carbon limitation promotes dormancy. Maximum dormancy duration is shorter under
      higher precipitation and at higher latitudes, the latter suggesting an important
      role for competition or herbivory. Study length affects estimates of some
      demographic parameters. Our results identify life historical and environmental
      drivers of dormancy. We also highlight the evolutionary importance of the little
      understood costs of sprouting and growth, latitudinal stress gradients and mixed
      nutritional modes.

PMID- 29575386
TI  - Involving private practitioners in the Indian tuberculosis programme: a
      randomised trial.
AB  - OBJECTIVES: To assess a multicomponent intervention to improve private
      practitioners (PPs) involvement in referral of presumptive pulmonary TB (PTB)
      cases to the Revised National TB Control Programme (RNTCP) for sputum
      examination. METHODS: Randomised controlled trial. We randomly allocated all 189
      eligible PPs in Tumkur city, South India, to intervention or control arm. The
      intervention, implemented between December 2014 and January 2016, included two
      sets of activities, one targeted at health system strengthening (building RNTCP
      staff capacity to collaborate with PPs, provision of feedback on referrals
      through SMS) and one targeted at intervention PPs (training in RNTCP, provision
      of referral pads and education materials and monthly visits to PPs by RNTCP
      staff). Crude and adjusted referral and PTB case-finding rate ratios were
      calculated with negative binomial regression. RESULTS: PPs referred 836
      individuals (548 from intervention and 169 from control arm PPs) of whom 176 were
      diagnosed with bacteriologically confirmed PTB. The proportion (95% confidence
      interval) of referring PPs [0.59 (0.49, 0.68) vs. 0.42 (0.32, 0.52) in the
      intervention and control arm, respectively], mean referral rate per PP-year [(5.7
      (3.8, 8.7) vs. 1.8 (1.2, 2.8)] and smear-positive PTB case-finding rate per PP
      year [(1.5 (0.9, 2.2) vs. 0.6 (0.3, 0.9)] were significantly higher in the
      intervention than the control arm. Stratifying by qualification, a statistically
      significant difference in the above indicators remained only among GPs and
      internists. Overall, surgeons, paediatricians and gynaecologists referred few
      patients. PP referrals contributed to 20% of the sputum smear positive PTB cases
      detected by RNTCP in Tumkur city (14% were from intervention arm PPs).
      CONCLUSIONS: We demonstrated the effectiveness of a health system-oriented
      intervention to improve PP's referrals of presumptive PTB cases to RNTCP.

PMID- 29575387
TI  - Indicators to facilitate the early identification of patients with major
      depressive disorder in need of highly specialized care: A concept mapping study.
AB  - BACKGROUND: Early identification of the subgroup of patients with major
      depressive disorder (MDD) in need of highly specialized care could enhance
      personalized intervention. This, in turn, may reduce the number of treatment
      steps needed to achieve and sustain an adequate treatment response. The aim of
      this study was to identify patient-related indicators that could facilitate the
      early identification of the subgroup of patients with MDD in need of highly
      specialized care. METHODS: Initial patient indicators were derived from a
      systematic review. Subsequently, a structured conceptualization methodology known
      as concept mapping was employed to complement the initial list of indicators by
      clinical expertise and develop a consensus-based conceptual framework. Subject
      matter experts were invited to participate in the subsequent steps
      (brainstorming, sorting, and rating) of the concept mapping process. A final
      concept map solution was generated using nonmetric multidimensional scaling and
      agglomerative hierarchical cluster analyses. RESULTS: In total, 67 subject-matter
      experts participated in the concept mapping process. The final concept map
      revealed the following 10 major clusters of indicators: 1-depression severity, 2
      onset and (treatment) course, 3-comorbid personality disorder, 4-comorbid
      substance use disorder, 5-other psychiatric comorbidity, 6-somatic comorbidity, 7
      maladaptive coping, 8-childhood trauma, 9-social factors, and 10-psychosocial
      dysfunction. CONCLUSIONS: The study findings highlight the need for a
      comprehensive assessment of patient indicators in determining the need for highly
      specialized care, and suggest that the treatment allocation of patients with MDD
      to highly specialized mental healthcare settings should be guided by the
      assessment of clinical and nonclinical patient factors.

PMID- 29575389
TI  - Optical Sensing of Aromatic Amino Acids and Dipeptides by a Crown-Ether
      Functionalized Perylene Bisimide Fluorophore.
AB  - The host-guest binding properties of a fluorescent perylene bisimide (PBI)
      receptor equipped with crown ether were studied in detail with a series of
      aromatic amino acids and dipeptides by UV/Vis, fluorescence and NMR spectroscopy.
      Fluorescence titration experiments showed that electron-rich aromatic amino acids
      and dipeptides strongly quench the fluorescence of the electron-poor PBI host
      molecule. Benesi-Hildebrand plots of fluorescence titration data confirmed the
      formation of host-guest complexes with 1:2 stoichiometry. Binding constants
      determined by global analysis of UV/Vis and fluorescence titration experiments
      revealed values between 103  m-1 and 105  m-1 in acetonitrile/methanol (9:1) at
      23  degrees C. These data showed that amino acid l-Trp having an indole group and
      dipeptides containing this amino acid bind to the PBI receptor more strongly than
      other amino acids and dipeptides investigated here. For dipeptides containing l
      Trp or l-Tyr, the binding strength is dependent on the distance between the
      ammonium group and the aromatic unit of the amino acids and dipeptides leading to
      a strong sensitivity for Ala-Trp dipeptide. 1D and 2D NMR experiments also
      corroborated 1:2 host-guest complexation and indicated formation of two
      diastereomeric species of host-guest complexes. The studies have shown that a
      properly functionalized PBI fluorophore functions as a molecular probe for the
      optical sensing of aromatic amino acids and dipeptides.

PMID- 29575388
TI  - The ecology of patient and caregiver participation in consultations involving
      advanced cancer.
AB  - OBJECTIVE: To identify predictors of participation of patients with advanced
      cancer in clinical encounters with oncologists and to assess the impact of
      patient and caregiver participation on perceptions of physician support. METHODS:
      This is a secondary data analysis from the Values and Options in Cancer Care
      study, a cluster randomized clinical trial of a patient-centered communication
      intervention. Patients and caregivers completed pre-visit and post-visit health
      and communication measures. Audio recorded patient-caregiver (when present)
      physician encounters were coded for active patient/caregiver participation
      behaviors (eg, question asking, expressing concern) and for physicians'
      facilitative communication (eg, partnership-building, support). Mixed linear
      regression models were used to identify patient, physician, and situational
      factors predicting patient and patient plus caregiver communication behaviors and
      post-visit outcomes. RESULTS: Physician partnership building predicted greater
      expressions of concern and more assertive responses from patients and patient
      caregiver pairs. Patients' perceptions of greater connectedness with their
      physician predicted fewer patient expressions of concern. Patient perceptions of
      physician respect for their autonomy were lower among patients accompanied by
      caregivers. Caregiver perceptions of physician respect for patient autonomy
      decreased with increasing patient age and varied by site. CONCLUSIONS: In
      advanced cancer care, patient and caregiver communication is affected by
      ecological factors within their consultations. Physicians can support greater
      patient participation in clinical encounters through facilitative communication
      such as partnership-building and supportive talk. The presence of a caregiver
      complicates this environment, but partnership building techniques may help
      promote patient and caregiver participation during these visits.

PMID- 29575391
TI  - Surface-Doped Polystyrene Microsensors Containing Lipophilic Solvatochromic Dye
      Transducers.
AB  - Ion-selective optical microsensors based on surface-modified polystyrene (PS)
      beads with positively charged lipophilic solvatochromic dye (SD) on the surface
      were studied with K+ as model ion. Water-soluble SDs are expelled into the
      aqueous phase by ion exchange with the cationic analyte of interest, resulting in
      a detectable color change. In contrast, lipophilic SDs are more attractive, as
      they appear to remain anchored to the surface after expulsion from the sensing
      phase. This transfers just the ionic chromophore functionality into the aqueous
      phase and allows the system to act as a reversible, truly self-contained sensor.
      In this work this mechanism was evaluated with zeta-potential measurements on
      microsensor suspensions. It indeed provides experimental evidence for the
      mechanism of SD transfer, as a reversal of the zeta-potential of the PS
      microsensors was observed for higher potassium concentrations with valinomycin
      doped microspheres. For a discriminated ion such as sodium, the zeta-potential
      change occurs at much higher electrolyte concentrations, in agreement with sensor
      selectivity. Undoped microspheres showed no apparent dependence of zeta-potential
      on electrolyte concentration. The study also shows that the effective range of
      microsensor surface charge is tunable and depends on the concentration of the SD
      on the coating phase.

PMID- 29575390
TI  - Metabolome analysis for pancreatic cancer risk in nested case-control study:
      Japan Public Health Center-based prospective Study.
AB  - Discovery of a high-risk group for pancreatic cancer is important for prevention
      of pancreatic cancer. The present study was conducted as a nested case-control
      study including 170 pancreatic cancer cases and 340 matched controls of our
      population-based cohort study involving 30 239 subjects who answered a baseline
      questionnaire and supplied blood samples. Twelve targeted metabolites were
      quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds
      ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated
      using conditional logistic regression models. Statistically significant P-value
      was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were
      associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4
      [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also
      associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79;
      95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders
      attenuated the observed associations of 1,5-AG and methionine (P for trend = .06
      and .07, respectively). Comparing subjects diagnosed in the first 0-6 years,
      higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing
      trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02,
      respectively), even after adjustment for potential confounders. We found that the
      12 target metabolites were not associated with pancreatic cancer risk. However,
      metabolic changes in the subjects diagnosed in the first 0-6 years showed a
      similar tendency to our previous reports. These results might suggest that these
      metabolites are useful for early detection but not for prediction of pancreatic
      cancer.

PMID- 29575392
TI  - Enhancement of teaching outcome through neural prediction of the students'
      knowledge state.
AB  - The neural mechanism for the dyadic process of teaching is poorly understood.
      Although theories about teaching have proposed that before any teaching takes
      place, the teacher will predict the knowledge state of the student(s) to enhance
      the teaching outcome, this theoretical Prediction-Transmission hypothesis has not
      been tested with any neuroimaging studies. Using functional near-infrared
      spectroscopy-based hyperscanning, this study measured brain activities of the
      teacher-student pairs simultaneously. Results showed that better teaching outcome
      was associated with higher time-lagged interpersonal neural synchronization (INS)
      between right temporal-parietal junction (TPJ) of the teacher and anterior
      superior temporal cortex (aSTC) of the student, when the teacher's brain activity
      preceded that of the student. Moreover, time course analyses suggested that such
      INS could mark the quality of the teaching outcome at an early stage of the
      teaching process. These results provided key neural evidence for the Prediction
      Transmission hypothesis about teaching, and suggested that the INS plays an
      important role in the successful teaching.

PMID- 29575393
TI  - Photodynamic inactivation of foodborne bacteria by eosin Y.
AB  - AIMS: The aim of this study was evaluate the effect of photodynamic inactivation
      mediated by eosin Y in Salmonella enterica serotype Typhimurium ATCC 14028,
      Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus
      aureus ATCC 25923 and Bacillus cereus ATCC 11778. METHODS AND RESULTS: Bacteria
      (107 CFU per ml) were incubated with eosin Y at concentrations ranging from 0.1
      to 10 MUmol l-1 , irradiated by green LED (lambdamax 490-570 nm) for 5, 10 and 15
      min and the cellular viability was determined. Pseudomonas aeruginosa was
      completely inactivated when treated with 10 MUmol l-1 eosin Y for 10 min.
      Treatments reduced B. cereus and Salm. Typhimurium counts to 2.7 log CFU per ml
      and 1.7 log CFU per ml, respectively. Escherichia coli counts were slightly
      reduced. Staphylococcus aureus presented the highest sensitivity, being
      completely inactivated by eosin Y at 5 MUmol l-1 and 5 min of illumination. The
      reduction of cellular viability of photoinactivated Staph. aureus was also
      demonstrated by flow cytometry and morphological changes were observed by
      scanning electron microscopy. CONCLUSIONS: Eosin Y in combination with LED
      produced bacterial inactivation, being a potential candidate for photodynamic
      inactivation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evidenced the
      efficacy of photodynamic inactivation as a novel and promising alternative to
      bacterial control.

PMID- 29575394
TI  - Islandinium minutum subsp. barbatum subsp. nov. (Dinoflagellata), a New Organic
      Walled Dinoflagellate Cyst from the Western Arctic: Morphology, Phylogenetic
      Position Based on SSU rDNA and LSU rDNA, and Distribution.
AB  - A study of modern sediment from the Western Arctic has revealed the presence of a
      distinctive brown-colored cyst with a spherical central body bearing unbranched
      processes that are usually solid with a small basal pericoel. Distinctive barbs
      project from some processes, and process tips are usually minutely expanded into
      conjoined barbs. The archeopyle is apical and saphopylic. This cyst corresponds
      to Islandinium? cezare morphotype 2 of Head et al. (2001, J. Quat. Sci., 16:621).
      Phylogenetic analyses based on the small and large subunit rRNA genes infer close
      relationship with Islandinium minutum, the type of which is that of the genus. Re
      examination of specimens of I. minutum reveals the presence of minute barbs on
      its processes, but differences with Islandinium? cezare morphotype 2 remain based
      on size, process distribution, and barb development. Furthermore, the internal
      transcribed spacer shows I. minutum to be distinct from this morphotype. On the
      basis of these small but discrete differences, we propose the new subspecies
      Islandinium minutum subsp. barbatum subsp. nov. Molecular sequencing of other
      cysts encountered, namely Echinidinium karaense, an unidentified flattened cyst,
      and "Polykrikos quadratus", places them in the Monovela clade, the latter showing
      greater morphological variability than previously thought.

PMID- 29575395
TI  - Cost-effectiveness of endobronchial valve treatment in patients with severe
      emphysema compared to standard medical care.
AB  - BACKGROUND AND OBJECTIVE: Bronchoscopic lung volume reduction using endobronchial
      valves (EBV) is an effective new treatment option for severe emphysema patients
      without interlobar collateral ventilation. The objective of this study was to
      perform an economic evaluation including the costs and cost-effectiveness of EBV
      treatment compared with standard medical care (SoC) from the hospital perspective
      in the short term and long term. METHODS: For the short-term evaluation,
      incremental cost-effectiveness ratios (ICER) were calculated based on the 6-month
      end point data from the STELVIO randomized trial. For the long-term evaluation, a
      Markov simulation model was constructed based on STELVIO and literature. The
      clinical outcome data were quality-adjusted life-years (QALY) based on the
      EuroQol5-Dimensions (EQ5D) questionnaire, the 6-min walking distance (6MWD) and
      the St George's Respiratory Questionnaire (SGRQ). RESULTS: The mean difference
      between the EBV group and controls was ?16 721/patient. In the short-term (6
      months), costs per additional QALY was ?205 129, the ICER for 6MWD was ?160 and
      for SGRQ was ?1241. In the long term, the resulting cost-effectiveness ratios
      indicate additional costs of ?39 000 per QALY gained with a 5-year time horizon
      and ?21 500 per QALY gained at 10 years. In comparison, historical costs per
      additional QALY 1 year after the coil treatment are ?738 400, 5 years after lung
      volume reduction surgery are ?48 415 and 15 years after double-lung
      transplantation are ?29 410. CONCLUSION: The positive clinical effects of EBV
      treatment are associated with increased costs compared with SoC. Our results
      suggest that the EBV treatment has a favourable cost-effectiveness profile, also
      when compared with other treatment modalities for this patient group.

PMID- 29575397
TI  - Localizing Antifungal Drugs to the Correct Organelle Can Markedly Enhance their
      Efficacy.
AB  - A critical aspect of drug design is optimal target inhibition by specifically
      delivering the drug molecule not only to the target tissue or cell but also to
      its therapeutically active site within the cell. This study demonstrates, as a
      proof of principle, that drug efficacy can be increased considerably by a
      structural modification that targets it to the relevant organelle. Specifically,
      by varying the fluorescent dye segment an antifungal azole was directed from the
      fungal cell mitochondria to the endoplasmic reticulum (ER), the organelle that
      harbors the drug target. The ER-localized azole displayed up to two orders of
      magnitude improved antifungal activity and also dramatically reduced the growth
      of drug-tolerant fungal subpopulations in a panel of Candida species, which are
      the most prevalent causes of serious human fungal infections. The principle
      underlying the "target organelle localization" approach provides a new paradigm
      to improve drug potency and replenish the limited pipeline of antifungal drugs.

PMID- 29575396
TI  - Changes in left ventricular strain parameters following pediatric heart
      transplantation.
AB  - STE is increasingly utilized to assess strain in a variety of pathologies. Strain
      measurements have demonstrated utility following HTx and may aid in the detection
      of rejection and CAV. Strain parameters have not been well defined in the
      pediatric HTx population. This study aimed to describe strain in pediatric HTx
      recipients compared to controls and assess changes over time. All pediatric HTx
      recipients with available echocardiograms (2004-2015) without rejection or CAV
      were identified. Longitudinal and circumferential strain was measured at <1
      month, 1 year, 3 years, and 5 years post-transplant and compared to controls. A
      total of 218 echocardiograms were analyzed in 79 HTx recipients. At <1 month post
      transplant, there was a significant decrement in longitudinal strain (GLS -14.6
      vs -19.2, P < .001) with concurrent augmentation of circumferential strain (GCS 
      27.3 vs -24.3, P = .005). By 1 year post-HTx, all strain parameters normalized
      and were not significantly different from the control population. In the absence
      of graft complications, strain parameters did not change up to 5 years post
      transplant. Abnormal longitudinal strain parameters are present in the early post
      HTx period with a compensatory increase in circumferential strain. These changes
      normalize by 1 year post-transplant and do not change over time in the absence of
      graft complications.

PMID- 29575398
TI  - Strong Photonic-Band-Gap Effect on the Spontaneous Emission in 3D Lead Halide
      Perovskite Photonic Crystals.
AB  - Stimulated emission in perovskite-embedded polymer opal structures is
      investigated. A polymer opal structure is filled with a perovskite, and
      perovskite photonic crystals are prepared. The spontaneous emission of the
      perovskite embedded in the polymer opal structures exhibits clear signatures of
      amplified spontaneous emission (ASE) via gain modulation. The difference in
      refractive-index contrast between the perovskite and the polymer opal is large
      enough for retaining photonic-crystals properties. The photonic band gap has a
      strong effect on the fluorescence emission intensity and lifetime. The stimulated
      emission spectrum exhibits a narrow ASE rather than a wide fluorescence peak in
      the thin film.

PMID- 29575399
TI  - Unique application of awake tracheoscopy and endobronchial ultrasound in the
      management of tracheal mucoepidermoid carcinoma.
AB  - BACKGROUND: Mucoepidermoid carcinoma of the trachea is a rare pediatric
      malignancy that presents unique challenges in diagnosis, operative management,
      and surveillance. METHODS AND RESULTS: We present a 17-year-old girl with primary
      tracheal mucoepidermoid carcinoma presenting in acute respiratory distress due to
      near-total occlusion of the tracheal airway. An algorithmic approach to
      preoperative planning was developed to evaluate and remove the tumor
      endoscopically without compromising oxygenation. After initial palliative
      resection, endobronchial ultrasound was uniquely applied to evaluate depth of
      tumor invasion, and subsequent tracheal resection with primary anastomosis was
      performed as curative treatment. CONCLUSION: Removal of distal tracheal masses
      can be performed safely with the implementation of an algorithmic approach to
      tumor visualization and resection. Endobronchial ultrasound can be used to
      evaluate the extent of tumor invasion and plan for definitive resection.

PMID- 29575400
TI  - Regression of left atrial diameter after kidney transplantation is associated
      with prolonged survival: an observational study.
AB  - Renal transplantation reduces the dramatically elevated risk of cardiovascular
      death in dialysis patients. We previously showed that left atrial diameter before
      transplantation predicts cardiovascular and overall mortality. Now, we
      investigated the association of changes in cardiac morphology after
      transplantation and mortality. We retrospectively analyzed data from the Austrian
      transplant repository using multivariable Cox and competing risk models and
      multivariable logistic regression for the prediction of changes in cardiac
      morphology. We identified 414 patients with a median follow-up of 8 years and
      observed a significant progression of mean diameter of left atrium (LA), right
      atrium and right ventricle and a significant regression of left ventricle.
      Complete case analysis of 243 patients with a regression of initially enlarged LA
      diameter had a significantly lower risk of adjusted overall and cardiovascular
      mortality; hazard ratio (HR 0.45, 95% CI 0.30-0.69, P < 0.001, 124 deaths), and
      HR of 0.43 [95% CI 0.21-0.92, P = 0.029, 48 cardiovascular (CV) deaths],
      respectively. Only age at transplantation was significantly associated with
      regression of LA (OR 0.75, 95% CI 0.60-0.93, P = 0.007). Patients with regression
      of LA after kidney transplantation exhibited a lower overall and CV mortality
      risk. Besides age, peritoneal dialysis and antihypertensive therapy were
      mediators of LA regression.

PMID- 29575401
TI  - Previously undiagnosed attention-deficit/hyperactivity disorder associated with
      poor metabolic control in adolescents with type 1 diabetes.
AB  - BACKGROUND: Managing modern diabetes treatment requires efficient executive
      functions. Patients with attention-deficit/hyperactivity disorder (ADHD) and type
      1 diabetes have poor metabolic control and present with ketoacidosis more often
      than patients without ADHD. OBJECTIVE: To assess whether patients with type 1
      diabetes and with indications of executive problems met criteria for ADHD, and to
      investigate whether these patients had difficulties achieving metabolic control.
      METHODS: In a hospital-based study, including 3 pediatric departments at
      hospitals in Stockholm and Uppsala, Sweden, questionnaires regarding executive
      problems had been filled out by 12- to 18-year-old patients with type 1 diabetes
      and their parents. Out of 166 patients with completed questionnaires, 49 were
      selected for a clinical study due to reported executive problems/ADHD symptoms.
      However, 7 already had a diagnosis of ADHD, 21 denied follow-up, 8 did not
      respond, leaving 13 adolescents for the clinical assessment. RESULTS: Of the
      clinically assessed adolescents, 9 (6 girls) met criteria for ADHD. Patients who
      did not respond to the follow-up and patients who were diagnosed with ADHD within
      the study, showed to a larger extent than the other study groups high HbA1c
      levels (>70 mmol/mol, 8,6%). HbA1c >70 mmol/mol (8.6%) was associated with
      diagnosed ADHD (prior to or within the study), odds ratio 2.96 (95% confidence
      interval 1.02-8.60). CONCLUSION: Patients with type 1 diabetes and poor metabolic
      control should be assessed with regard to ADHD. There is a need for paying
      special attention to girls with poor metabolic control.

PMID- 29575402
TI  - Mechanical Switching of Aromaticity and Homoaromaticity in Molecular Optical
      Force Sensors for Polymers.
AB  - The sensing of mechanical stress in polymers is indispensable for investigating
      the origin and propagation of cracks that lead to material failure and for
      designing mechanically responsive polymers. Here the unique approaches of using
      the force-induced switching of aromaticity and homoaromaticity in molecular
      optical force sensors for the real-time measurement of mechanical forces acting
      in stretched polymers are suggested. The mechanical switching of aromaticity in
      Dewar benzene is an irreversible event, whereas the degree of pi-orbital overlap
      in homoaromatic compounds like homotropylium can be adjusted progressively over a
      wide range of forces. Using computational methods, it is demonstrated that both
      approaches lead to significant changes in the visible part of the UV/Vis spectra
      of the force sensors upon application of weak forces (pN-nN). Polymers that
      incorporate such molecular force sensors therefore change their color well before
      material failure occurs.

PMID- 29575403
TI  - Celebrating 50 years of the Primate Society of Great Britain.

PMID- 29575404
TI  - Frequency and intensity of pyrethroid resistance through the CDC bottle bioassay
      and their association with the frequency of kdr mutations in Aedes aegypti
      (Diptera: Culicidae) from Mexico.
AB  - BACKGROUND: The control of Aedes aegypti (L.), the main urban vector that causes
      arboviral diseases such as dengue, Chikungunya and Zika, has proved to be a
      challenge because of a rapid increase in insecticide resistance. Therefore,
      adequate monitoring of insecticide resistance is an essential element in the
      control of Ae. aegypti and the diseases it transmits. We estimated the frequency
      and intensity (Resistance Frequency Rapid Diagnostic Test [F-RDT] and Resistance
      Intensity Rapid Diagnostic Test [I-RDT]) of pyrethroid resistance in populations
      of Ae. aegypti from Mexico using the bottle bioassay and results were related to
      the frequencies of knockdown resistance (kdr) mutations V1016I and F1534C.
      RESULTS: All populations under study were resistant to the pyrethroids:
      bifenthrin (99%), d-(cis-trans)-phenothrin (6.3% cis, 91.7% trans) and permethrin
      (99.5%) according to F-RDT, and showed moderate to high-intensity resistance at
      10* the diagnostic dose (DD) in I-RDT. Frequencies of the kdr mutation V1016I in
      Ae. aegypti populations were correlated with moderate permethrin resistance at
      10* DD, whereas F1534C mutation frequencies were correlated with high bifenthrin
      resistance at 5* DD. Both I1016 and C1535 were highly correlated with high
      intensity phenothrin resistance at 1* to 10* DD. CONCLUSIONS: This study showed
      that high frequencies of kdr mutations V1016I and F1534C are reflected in the
      results of F-RDT and I-RDT tests. Bioassays in conjunction with the
      characterization of genetic resistance mechanisms are indispensable in the
      strategic and rational management of resistance in mosquitoes. (c) 2018 Society
      of Chemical Industry.

PMID- 29575405
TI  - In vitro differentiation of bovine bone marrow-derived mesenchymal stem cells
      into male germ cells by exposure to exogenous bioactive factors.
AB  - Mesenchymal stem cells (MSC) are multipotent progenitor cells defined by their
      ability to self-renew and give rise to differentiated progeny. Previous studies
      have reported that MSC may be induced in vitro to develop into different types of
      specialized cells including male gametes. In vitro gamete derivation technology
      has potential applications as an alternative method for dissemination of elite
      animal genetics, production of transgenic animals and conservation of endangered
      species. This study aimed at investigating the in vitro effect of BMP4, TGFbeta1
      and RA on the potential for germ cell (GC) differentiation of bovine foetal MSC
      (bfMSC) derived from bone marrow (BM). The effect of BMP4, TGFbeta1 and RA was
      analysed on the expression of pluripotent, GC and male GC markers on bfMSC during
      a 21-day culture period. bfMSC cultured under in vitro conditions expressed OCT4,
      NANOG and DAZL, but lacked expression of mRNA of VASA, STELLA, FRAGILIS, STRA8
      and PIWIL2. Treatment with exogenous BMP4 and TGFbeta1 induced a transient
      increase (p < .05) in DAZL and NANOG mRNA levels, respectively. However, exposure
      to RA was more effective in increasing (p < .05) expression of DAZL and
      regulating expression of OCT4 and mRNA levels of NANOG. These data suggest that
      bfMSC may possess potential for early GC differentiation, where OCT4, NANOG and
      specially DAZL may play significant roles in controlling progression along the GC
      lineage.

PMID- 29575406
TI  - Knee-high compression socks minimize head-up tilt-induced cerebral and
      cardiovascular responses following dynamic exercise.
AB  - In healthy individuals during a non-exercised state, knee-high compression socks
      (CS) may reduce the magnitude of lower limb venous pooling during orthostasis but
      are not effective at minimizing the incidence of pre-syncopal symptoms. However,
      exaggerated reductions in cerebral blood flow velocity (CBV) and cardiac stroke
      volume (SV) occur during passive head-up tilt (HUT) testing following dynamic
      exercise. It is unknown if CS can minimize post-exercise HUT-induced decrements
      in CBV and SV in this population. To test the hypothesis that CS will attenuate
      the reductions in SV and CBV during 60 degrees  HUT following 60 minutes of
      moderate-intensity (60% VO2 peak) cycling exercise. Ten healthy volunteers (22.6
      +/- 2.1 years, 24.1 +/- 2.5 kg/m2 ) completed pre- and post-exercise 15-minute
      HUT tests during randomized CS and Control (no CS) conditions. Changes in blood
      pressure (finger plethysmography), SV (Modelflow(r) method), and CBV
      (Transcranial Doppler) were measured during HUT and preceding supine rest
      periods. Pre-exercise HUT-induced similar (all, P > .47) reductions in SV
      (Control; -23.1 +/- 11.5%, CS; -20.5 +/- 10.9%) and CBV (Control; -18.1 +/- 6.3%,
      CS; -15.3 +/- 9.0%). However, larger post-exercise decreases in SV and CBV during
      HUT were observed in the Control versus CS condition. Specifically, CS attenuated
      the drop in SV (Control: -32.9 +/- 5.6%, CS: -24.3 +/- 11.6%; P = .01) and CBV
      (Control: -25.1 +/- 5.8%, CS: -17.6 +/- 7.8%; P = .02) during the post-exercise
      HUT test. These results indicate that CS attenuated HUT-induced reductions in SV
      and CBV following moderate-intensity cycling exercise and suggest that CS may be
      an effective countermeasure to reduce the incidence of post-exercise syncope in
      vulnerable populations.

PMID- 29575407
TI  - The evolution of individuality revisited.
AB  - Evolutionary theory is formulated in terms of individuals that carry heritable
      information and are subject to selective pressures. However, individuality itself
      is a trait that had to evolve - an individual is not an indivisible entity, but a
      result of evolutionary processes that necessarily begin at the lower level of
      hierarchical organisation. Traditional approaches to biological individuality
      focus on cooperation and relatedness within a group, division of labour, policing
      mechanisms and strong selection at the higher level. Nevertheless, despite
      considerable theoretical progress in these areas, a full dynamical first
      principles account of how new types of individuals arise is missing. To the
      extent that individuality is an emergent trait, the problem can be approached by
      recognising the importance of individuating mechanisms that are present from the
      very beginning of the transition, when only lower-level selection is acting. Here
      we review some of the most influential theoretical work on the role of
      individuating mechanisms in these transitions, and demonstrate how a lower-level,
      bottom-up evolutionary framework can be used to understand biological complexity
      involved in the origin of cellular life, early eukaryotic evolution, sexual life
      cycles and multicellular development. Some of these mechanisms inevitably stem
      from environmental constraints, population structure and ancestral life cycles.
      Others are unique to specific transitions - features of the natural history and
      biochemistry that are co-opted into conflict mediation. Identifying mechanisms of
      individuation that provide a coarse-grained description of the system's
      evolutionary dynamics is an important step towards understanding how biological
      complexity and hierarchical organisation evolves. In this way, individuality can
      be reconceptualised as an approximate model that with varying degrees of
      precision applies to a wide range of biological systems.

PMID- 29575408
TI  - Studies with Ray Guillery on the early development of the visual pathways:
      eyecup, optic nerve, chiasm and optic tract.

PMID- 29575409
TI  - Comment on a paper by Sanchez-Larsen A et al. 'Assessment of efficacy and safety
      of eslicarbazepine acetate for the treatment of trigeminal neuralgia'.

PMID- 29575410
TI  - Performance of the St George's Respiratory Questionnaire in patients with
      connective tissue disease-associated interstitial lung disease.
AB  - BACKGROUND AND OBJECTIVE: The St George's Respiratory Questionnaire (SGRQ) is a
      self-administered questionnaire used to assess health-related quality of life
      (HRQoL) in various chronic respiratory diseases. Few studies have assessed the
      performance of the SGRQ in patients with connective tissue disease-associated
      interstitial lung disease (CTD-ILD). We aimed to examine the SGRQ's performance
      characteristics and generate data to support its reliability and validity in
      patients with CTD-ILD. METHODS: We used data from 193 CTD-ILD patients evaluated
      at Tosei General Hospital from May 2007 to July 2016 to assess the cross
      sectional and longitudinal validity of the SGRQ. RESULTS: The mean age of the
      patients was 64.2 years and 122 (63.2%) were women. There were no significant
      differences in SGRQ scores between any of the CTD groups. Internal consistency
      (Cronbach's alpha = 0.905) and repeatability (intraclass correlation coefficient
      (ICC) = 0.873) for the SGRQ total score were excellent. At baseline, SGRQ total
      score was significantly associated with clinically meaningful measures of
      physiological function, exercise capacity and dyspnoea. Change in SGRQ total
      score over 6 months was also associated with change in other measures. Cox
      proportional hazards models showed that higher baseline SGRQ total score was a
      significant predictor of mortality. The estimated minimal clinically important
      difference of SGRQ total score was 4-13 points. CONCLUSION: These data support
      the validity and reliability of SGRQ as a sensitive measure for capturing HRQoL
      in patients with CTD-ILD.

PMID- 29575411
TI  - Matrix-assisted laser desorption/ionization imaging mass spectrometry of
      intraperitoneally injected danegaptide (ZP1609) for treatment of stroke
      reperfusion injury in mice.
AB  - RATIONALE: This work focuses on direct matrix-assisted laser
      desorption/ionization imaging mass spectrometry (MALDI-IMS) detection of
      intraperitoneally (IP)-injected dipeptide ZP1609 in mouse brain tissue. Direct
      analysis of drug detection in intact tissue sections provides distribution
      information that can impact drug development. MALDI-IMS capabilities of
      uncovering drug transport across the blood-brain barrier are demonstrated.
      METHODS: Successful peptide detection using MALDI-IMS was achieved using a MALDI
      TOF/TOF system. Upon optimization of sample preparation procedures for dipeptide
      ZP1609, an additional tissue acidification procedure was found to greatly enhance
      signal detection. The imaging data acquired was able to determine successful
      transport of ZP1609 across the blood-brain barrier. Data obtained from MALDI-IMS
      can help shape our understanding of biological functions, disease progression,
      and effects of drug delivery. RESULTS: Direct detection of ZP1609 throughout the
      brain tissue sections was observed from MALDI-MS images. However, in cases where
      there was induction of stroke, a peak of lower signal intensity was also detected
      in the target m/z region. Although distinct differences in signal intensity can
      be seen between control and experimental groups, fragments and adducts of ZP1609
      were investigated using MALDI-IMS to verify detection of the target analyte.
      CONCLUSIONS: Overall, the data reveals successful penetration of ZP1609 across
      the blood-brain barrier. The benefits of tissue acidification in the enhancement
      of detection sensitivity for low-abundance peptides were demonstrated. MALDI-IMS
      has been shown to be a useful technique in the direct detection of drugs within
      intact brain tissue sections.

PMID- 29575413
TI  - Rising synchrony controls western North American ecosystems.
AB  - Along the western margin of North America, the winter expression of the North
      Pacific High (NPH) strongly influences interannual variability in coastal
      upwelling, storm track position, precipitation, and river discharge. Coherence
      among these factors induces covariance among physical and biological processes
      across adjacent marine and terrestrial ecosystems. Here, we show that over the
      past century the degree and spatial extent of this covariance (synchrony) has
      substantially increased, and is coincident with rising variance in the winter
      NPH. Furthermore, centuries-long blue oak (Quercus douglasii) growth chronologies
      sensitive to the winter NPH provide robust evidence that modern levels of
      synchrony are among the highest observed in the context of the last 250 years.
      These trends may ultimately be linked to changing impacts of the El Nino Southern
      Oscillation on midlatitude ecosystems of North America. Such a rise in synchrony
      may destabilize ecosystems, expose populations to higher risks of extinction, and
      is thus a concern given the broad biological relevance of winter climate to
      biological systems.

PMID- 29575412
TI  - Understanding access to healthcare among Indigenous peoples: A comparative
      analysis of biomedical and postcolonial perspectives.
AB  - As nursing professionals, we believe access to healthcare is fundamental to
      health and that it is a determinant of health. Therefore, evidence suggesting
      access to healthcare is problematic for many Indigenous peoples is concerning.
      While biomedical perspectives underlie our current understanding of access,
      considering alternate perspectives could expand our awareness of and ability to
      address this issue. In this paper, we critique how access to healthcare is
      understood through a biomedical lens, how a postcolonial theoretical lens can
      extend that understanding, and the subsequent implications this alternative view
      raises for the nursing profession. Drawing on peer-reviewed published and gray
      literature concerning healthcare access and Indigenous peoples to inform this
      critique, we focus on the underlying theoretical lens shaping our current
      understanding of access. A postcolonial analysis provides a way of understanding
      healthcare as a social space and social relationship, presenting a unique
      perspective on access to healthcare. The novelty of this finding is of particular
      importance for the profession of nursing, as we are well situated to influence
      these social aspects, improving access to healthcare services broadly, and among
      Indigenous peoples specifically.

PMID- 29575415
TI  - Gastrointestinal dysmotility: A qualitative exploration of the journey from
      symptom onset to diagnosis.
AB  - BACKGROUND: Gastrointestinal dysmotility (GID) covers a spectrum of disorders
      disrupting enteric neuromuscular co-ordination which, when severe, causes
      intractable gastrointestinal symptoms and malnutrition and is a recognized cause
      of chronic intestinal failure. To date, no study has provided an in-depth account
      of the experiences of patients with severe GID and their psychosocial needs. This
      study aimed to explore patients' experiences from symptom onset and the process
      of seeking and receiving a diagnosis. It specifically explored the psychological
      effect of this process and the effect on relationships. METHODS: Participants (n
      = 20, mean age = 47.9, female n = 16, parenteral nutrition = 13) were recruited
      from a UK center with tertiary Neurogastroenterology and Intestinal Failure
      services. A qualitative exploratory design with semi-structured in-depth
      interviews was used. Data were analyzed using thematic analysis. KEY RESULTS:
      Significant delays were experienced in obtaining a diagnosis. Participants
      reported having their mental health questioned and felt that they had to fight to
      prove their symptoms had a physical basis to access appropriate treatment.
      Although a diagnosis helped legitimize symptoms, the condition remained poorly
      understood by participants themselves, relatives, and health professionals.
      Participants discussed the impact that "feeling delegitimized" and the "lack of
      coherent understanding of GID" had on their relationships and mental health.
      CONCLUSIONS & INFERENCES: The distressing experience of GID symptoms are
      compounded by a delay in validating symptoms and lack of coherent understanding.
      More knowledge of GID is needed by health professionals to speed up diagnosis and
      offer more coherent information. The psychological impact of a GID diagnosis
      should be acknowledged early to help facilitate adjustment.

PMID- 29575414
TI  - Evidence for the Role of Intracellular Water Lifetime as a Tumour Biomarker
      Obtained by In Vivo Field-Cycling Relaxometry.
AB  - It was established through in vivo T1 measurements at low magnetic fields that
      tumour cells display proton T1 values that are markedly longer than those shown
      by healthy tissue. Moreover, it has been found that the elongation of T1
      parallels the aggressiveness of the investigated tumour. The T1 lengthening is
      associated with an enhanced water exchange rate across the transcytolemmal
      membrane through an overexpression/upregulation of GLUT1 and Na+ /K+ ATPase
      transporters. It follows that the intracellular water lifetime represents a
      hallmark of tumour cells that can be easily monitored by measuring T1 at
      different magnetic field strengths ranging from 0.2 to 200 mT.

PMID- 29575416
TI  - Au57 Ag53 (C=CPh)40 Br12 : A Large Nanocluster with C1 Symmetry.
AB  - The controlled synthesis and structure determination of a bimetallic nanocluster
      Au57 Ag53 (C=CPh)40 Br12 (Au57 Ag53 ) is presented. The metal core has a four
      shell Au2 M3 @Au34 @Ag51 @Au20 (M=1/3 Au+2/3 Ag) architecture. In contrast to the
      previously reported large nanoclusters that have highly symmetric kernel
      structures, the metal atoms in Au57 Ag53 are arranged in an irregular manner with
      C1 symmetry. This cluster exhibits excellent thermal stability and is robust
      under oxidative or basic conditions. The silver precursors play a key role in
      dictating the structures of the nanoclusters, which suggests the importance of
      the counteranions used.

PMID- 29575418
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 14/2018.

PMID- 29575417
TI  - Translation and validation study for the stroke self-efficacy questionnaire in
      stroke survivors.
AB  - BACKGROUND: Self-efficacy has been shown to play an important role in
      rehabilitation outcomes of stroke patients. AIM: This study aimed to determine
      the validity and reliability of a Turkish translation of the Stroke Self-Efficacy
      Questionnaire. METHODS: This methodological study was conducted in a private
      acute stroke unit in Istanbul, Turkey. After obtaining the Institutional Review
      Board's approval and site consent, a translated version of the 13-item Likert
      type scaled questions was tested for language and content validity. A pilot study
      with 10 patients was followed by recruitment of 130 stroke patient participants,
      with 50 patients retested after 3 weeks. RESULTS: The Stroke Self-Efficacy
      Questionnaire-Turkish had excellent content validity index and face validity
      index scores. Confirmatory factor analysis findings revealed a single factor
      structure that offered good model suitability. Cronbach alpha was 0.93 for the
      scale and its subgroups. There was no statistically significant difference
      between the items according to test-retest scores (P > 0.05), and a reliability
      index was over 0.80. CONCLUSION: The Turkish version of the Stroke Self-Efficacy
      Questionnaire is a valid and reliable tool, recommended for use in clinical
      rehabilitation and stroke self-management/self-efficacy interventions.

PMID- 29575419
TI  - Forty-nine cases of acute lymphoblastic leukaemia/lymphoma in pleural and
      pericardial effusions: A cytological-histological correlation.
AB  - INTRODUCTION: Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive
      entity of precursor lymphoid neoplasm and may cause malignant serous effusion
      (SE). The current study aimed to analyse the characteristics of SE cytology of
      ALL/LBL including cytomorphology, immunophenotyping, clonality and evaluate the
      effectiveness of SE cytology as a diagnostic method for ALL/LBL. METHODS: SE
      specimens with final diagnosis of ALL/LBL from 2006 to 2016 were reviewed for
      clinical data, cytomorphological features and ancillary studies. Cytodiagnoses
      were compared with histodiagnoses, and the discordant cases were analysed.
      RESULTS: A total of 49 specimens including 47 pleural fluids and 2 pericardial
      fluids from 49 patients were evaluated. Cytomorphology revealed lymphoblasts
      varied from small size with scant cytoplasm, condensed nuclear chromatin and
      indistinct nucleoli to large size with dispersed nuclear chromatin and multiple
      variably prominent nucleoli. Nuclear clefts and hand mirror-shaped blasts were
      demonstrated. The positive rates of CD99 and terminal deoxynucleotidyl
      transferase were 90.9% and 81.6%, respectively. Both monoclonal immunoglobulin
      (Ig)H and T-cell receptor-gamma gene rearrangements were demonstrated in 1 of 3
      cases. Monoclonal T-cell receptor-gamma gene rearrangement was found in 10 of 11
      cases. Monoclonal IgH and/or Ig? gene rearrangements were revealed in 2 of 3
      cases. Cytodiagnoses included 4 ALL/LBL, 3 B-ALL/LBL and 42 T-ALL/LBL.
      Histodiagnoses were available in 24 cases including 2 ALL/LBL, 2 B-ALL/LBL and 20
      T-ALL/LBL. The concordance rates of cytological-histological diagnoses were
      66.7%, 0% and 95.2% in the three categories, respectively. There were 3 cases
      with discrepancies of cell lineages. CONCLUSIONS: SE cytological evaluation is a
      reliable and effective method for the diagnosis of ALL/LBL.

PMID- 29575420
TI  - Rehydration before wet fixation in conventional body fluid cytology - An 18-year
      experience.
AB  - PURPOSE: In conventional cytology, preparation of a specimen by wet fixation for
      Papanicolaou stain is potentially subject to dry effect or cell loss which may
      make cytologic interpretation difficult or even impossible. We have been
      routinely making an additional smear for rehydration with normal saline
      (rehydration method) before wet fixation to overcome the above shortcomings.
      METHODS: We reviewed malignant pleural effusion and ascites 15 cases each in our
      cytology laboratory over the past 1 year. Four slides of each specimen were made.
      Two were air-dried for Liu's stain (a Romanowsky stain) and the other two were
      wet-fixed for Papanicolaou stain. The air-dried smears were also served as
      retained cellularity control. One of the two wet-fixed smears was processed as a
      control of preservation of nuclear detail whereas the other one stayed air-dried
      for 10 minutes and then covered with normal saline (rehydration method) for 80
      seconds before wet fixation. RESULTS: There was minor cell loss (P = .032). The
      cells appeared larger with good preservation of nuclear detail (P < .0001 by two
      sided Wilcoxon rank sum test) but no red blood cells retained on the slide after
      rehydration. CONCLUSION: The rehydration method can effectively minimise cell
      loss, enlarge and preserve the cytological features of malignant cells with
      haemolysis. This method is simple, practical and good for cytological screening
      for tumour cells and interpretation especially in a bloody smear. We recommend
      that the rehydration method be part of traditional cytopreparatory work of wet
      fixation for Papanicolaou stain in conventional body fluid cytology.

PMID- 29575422
TI  - Differentiated cervical intraepithelial neoplasia-associated invasive cervical
      squamous cell carcinoma as a source of major cytopathological and surgical
      pathological discrepancy in Papanicolaou smear screening tests.
AB  - INTRODUCTION: Differentiated cervical intraepithelial neoplasia (dCIN) analogous
      to differentiated squamous intraepithelial neoplasia of the vulva is
      characterised by the proliferation of atypical cells limited to the
      basal/parabasal layers. Exfoliative cytology of dCIN has not been investigated.
      METHODS AND RESULTS: A 46-year-old woman, with a history of normal Papanicolaou
      (Pap) smear up to 2 years prior to the occurrence of postcoital vaginal bleeding
      had two consecutive Pap smears, which only revealed atypical squamous cells of
      unknown significance (ASCUS). The subsequent cervical biopsy revealed dCIN. The
      cone biopsy showed the invasive cervical squamous cell carcinoma (ICC) that
      developed from the overlying dCIN. Review of 32 consecutive cases of ICC revealed
      a second case of dCIN-associated ICC (Group 1) preceded by ASCUS suspicious for
      high-grade neoplastic cells. In both cases, the ASCUS were keratinised atypical
      cells without koilocytosis. In addition, there were another seven cases showing
      focal dCIN associated with extensive usual CIN (Group 2). In comparison with the
      remaining 24 cases with usual CIN (Group 3), Group 2 lesions occurred in younger
      patients (mean ages of 36 +/- 3 vs 47 +/- 9 years) and were associated with
      shorter intervals after the last normal Pap smears. Pap smears in Group 2
      occasionally consisted only of ASCUS cells. CONCLUSIONS: dCIN may occur in the
      cervix and accounts for a short interval of normal Pap smears and false negative
      or low-grade Pap smears in ICC.

PMID- 29575423
TI  - Cytological preparations for molecular analysis: A review of technical
      procedures, advantages and limitations for referring samples for testing.
AB  - Minimally invasive procedures such as endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) must yield not only good quality and
      quantity of material for morphological assessment, but also an adequate sample
      for analysis of molecular markers to guide patients to appropriate targeted
      therapies. In this context, cytopathologists worldwide should be familiar with
      minimum requirements for refereeing cytological samples for testing. The present
      manuscript is a review with comprehensive description of the content of the
      workshop entitled Cytological preparations for molecular analysis: pre-analytical
      issues for EBUS TBNA, presented at the 40th European Congress of Cytopathology in
      Liverpool, UK. The present review emphasises the advantages and limitations of
      different types of cytology substrates used for molecular analysis such as
      archival smears, liquid-based preparations, archival cytospin preparations and
      FTA (Flinders Technology Associates) cards, as well as their technical
      requirements/features. These various types of cytological specimens can be
      successfully used for an extensive array of molecular studies, but the quality
      and quantity of extracted nucleic acids rely directly on adequate pre-analytical
      assessment of those samples. In this setting, cytopathologists must not only be
      familiar with the different types of specimens and associated technical
      procedures, but also correctly handle the material provided by minimally invasive
      procedures, ensuring that there is sufficient amount of material for a precise
      diagnosis and correct management of the patient through personalised care.

PMID- 29575424
TI  - Microarray Analysis of Oligosaccharide-Mediated Multivalent Carbohydrate-Protein
      Interactions and Their Heterogeneity.
AB  - Carbohydrate-protein interactions (CPIs) are involved in a wide range of
      biological phenomena. Hence, the characterization and presentation of
      carbohydrate epitopes that closely mimic the natural environment is one of the
      long-term goals of glycosciences. Inspired by the multivalency, heterogeneity and
      nature of carbohydrate ligand-mediated interactions, we constructed a
      combinatorial library of mannose and galactose homo- and hetero-glycodendrons to
      study CPIs. Microarray analysis of these glycodendrons with a wide range of
      biologically important plant and animal lectins revealed that oligosaccharide
      structures and heterogeneity interact with each other to alter binding
      preferences.

PMID- 29575425
TI  - Degrees of functional connectome abnormality in disorders of consciousness.
AB  - Understanding the neuronal basis of disorders of consciousness can help improve
      the accuracy of their diagnosis, indicate potential targets for therapeutic
      interventions, and provide insights into the organization of normal conscious
      information processing. Measurements of brain activity have been used to find
      associations of the levels of consciousness with brain complexity, topological
      features of functional connectomes, and disruption of resting-state networks.
      However, obtainment of a detailed picture of activity patterns underlying the
      vegetative state/unresponsive wakefulness syndrome and the minimally conscious
      state remains a work in progress. We here aimed at finding the aspects of fMRI
      based functional connectivity that differentiate these states from each other and
      from the normal condition. A group of 22 patients was studied (9 minimally
      conscious state and 13 vegetative state/unresponsive wakefulness syndrome).
      Patients were shown to have reduced connectivity in most resting-state networks
      and disrupted patterns of relative connection strengths as compared to healthy
      subjects. Differences between the unresponsive wakefulness syndrome and the
      minimally conscious state were found in the patterns formed by a relatively small
      number of strongest positive correlations selected by thresholding. These
      differences were captured by measures of functional connectivity disruption that
      integrate area-specific abnormalities over the whole brain. The results suggest
      that the strong positive correlations between the functional activities of
      specific brain areas observed in healthy individuals may be critical for
      consciousness and be an important target of disruption in disorders of
      consciousness.

PMID- 29575426
TI  - Satisfaction guaranteed? Forensic consumer satisfaction survey.
AB  - Despite many people being forensically hospitalized worldwide, there is limited
      research reporting on their views of the care they receive. To describe consumer
      satisfaction and areas for improvement, we utilized our forensic psychiatric
      hospital's consumer survey. Eleven years of surveys, including a total of 541
      surveys, were analysed both quantitatively and qualitatively. The majority of the
      forensic inpatients believed that their views were valued in their care and
      treatment. Most felt physically and emotionally safe at the hospital and believed
      that staff knew how to support them in times of distress. The majority felt that
      their culture and spirituality were respected. However, some areas for
      improvement were also noted, such as regarding staff attitudes. This consumer
      survey demonstrated a reasonably high level of satisfaction with forensic
      inpatient care, over the course of eleven years, despite this population of
      people being subject to lengthy hospitalisations. Satisfaction surveys of people
      in forensic inpatient units can be a regular part of forensic care and can help
      guide improvements in their care.

PMID- 29575427
TI  - A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with
      Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast
      Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window.
AB  - A novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI)
      contrast agent was developed, based on core-shell lanthanide fluoride
      nanoparticles composed of a beta-NaHoF4 core plus a beta-NaGdF4:Yb3+ , Tm3+ shell
      with an average size of ~24 nm. The biocompatibility of the particles was ensured
      by a surface modification with poly acrylic acid (PAA) and further
      functionalization with an affinity ligand, folic acid (FA). When excited using
      980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense
      emission at 802 nm with lifetime of 791+/-3 MUs, due to the transition 3 H4 ->3
      H6 of Tm3+ . Proton nuclear magnetic relaxation dispersion (1 H-NMRD) studies and
      magnetic resonance (MR) phantom imaging showed that the newly synthesized
      nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface
      (NP-PAA-FA), can act mainly as a T1 -weighted contrast agent below 1.5 T, a T1
      /T2 dual-weighted contrast agent at 3 T, and as highly efficient T2 -weighted
      contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low
      cytotoxicity and no detectable cellular damage up to a dose of 500 MUg mL-1 .

PMID- 29575428
TI  - Identification of Candida albicans regulatory genes governing mucosal infection.
AB  - The fungus Candida albicans thrives on a variety of human mucosae, yet the fungal
      determinants that contribute to fitness on these surfaces remain underexplored.
      Here, by screening a collection of C. albicans deletion strains in a mouse model
      of oral infection (oropharyngeal candidiasis), we identify several novel
      regulatory genes that modulate the fitness of the fungus in this locale. We
      investigate in detail the interplay between the host mucosa and one of the
      identified mutants and establish that the C. albicans transcription regulator
      CUP9 is a key determinant of mucosal colonisation. Deletion of cup9 resulted in
      the formation of more foci of colonisation and heightened persistence in infected
      tongues. Furthermore, the cup9 mutant produced longer and denser filaments in the
      oral mucosa without eliciting an enhanced local immune response. Consistent with
      its role in oral colonisation, we show that CUP9's top target of regulation is a
      major effector of Candida's adherence to buccal cells. Finally, we establish that
      CUP9 also governs the interplay of the fungus with vaginal epithelial cells and
      has a role in vaginal infections, another common mucosal disease associated with
      Candida. Thus, our findings reveal a mechanism whereby C. albicans can regulate
      proliferation on mucosal surfaces.

PMID- 29575429
TI  - Alkyl Ethers as Traceless Hydride Donors in Bronsted Acid Catalyzed
      Intramolecular Hydrogen Atom Transfer.
AB  - A new protocol for the deoxygenation of alcohols and the hydrogenation of alkenes
      under Bronsted acid catalysis has been developed. The method is based on the use
      of either a benzyl or isopropyl ether as a traceless hydrogen-atom donor, and
      involves an intramolecular hydride transfer as a key step, which is achieved in a
      regio- and stereoselective manner.

PMID- 29575430
TI  - Improvement of mimetic peroxidase activity of gold nanoclusters on the luminol
      chemiluminescence reaction by surface modification with ethanediamine.
AB  - Peroxidase is a commonly used catalyst in luminol-H2 O2 chemiluminescence (CL)
      reactions. Natural peroxidase has a sophisticated separation process, short shelf
      life and unstable activity, therefore it is important to develop peroxidases that
      have both high catalytic activity and good stability as alternatives to the
      natural enzyme. Gold nanoclusters (Au NCs) are an alternative peroxidase with
      catalytic activity in the luminol-H2 O2 CL reaction. In the present study,
      ethanediamine was modified on the surface of Au NCs forming cationic Au NCs. The
      zeta potential of the cationic Au NCs maintained its positive charge when the pH
      of the solution was between 4 and 9. The cationic Au NCs showed higher catalytic
      activity in the luminol-H2 O2 CL reaction than did unmodified Au NCs. A mechanism
      study showed that the better performance of cationic Au NCs may be attributed to
      the generation of 1 O2 on the surface of cationic Au NCs and a positive surface
      charge, for better affinity to luminol. Cationic Au NC, acting as a peroxidase
      mimic, has much better stability than horseradish peroxidase over a wide range of
      temperatures. We believe that cationic Au NCs may be useful as an artificial
      peroxidase for a wide range of potential applications in CL and bioanalysis.

PMID- 29575431
TI  - Integrated transcriptomic and proteomic analyses reveal alpha-lipoic acid
      regulated cell proliferation via Grb2-mediated signalling in hepatic cancer
      cells.
AB  - Hepatocellular carcinoma is the most frequent primary liver cancer worldwide. The
      use of antioxidants as cancer prevention and treatment agents has become a focus
      of research in recent years due to their limited adverse effects. Alpha lipoic
      acid (alpha-LA) is synthesized in the liver and is considered a naturally
      occurring antioxidant. In this study, a total of 4446 differentially expressed
      genes (2097 down-regulated and 2349 up-regulated) were identified via RNA-Seq in
      HepG2 cells after exposure to alpha-LA for 24 hrs. Moreover, GO and KEGG pathway
      analyses showed that cancer-relevant cell membrane proteins were significantly
      affected. An interaction network analysis predicted that Grb2 might mediate the
      key target pathways activated by exposure to alpha-LA. Verification of the RNA
      Seq and iTRAQ results confirmed that Grb2 mediated the alpha-LA-induced
      inhibition of cell proliferation in vitro. Furthermore, the analysis of human
      hepatocellular carcinoma specimens obtained from the GEO database showed that the
      expression of EGFR and Met correlated with that of Grb2. These findings provide a
      novel mechanism through which alpha-LA regulates cell proliferation via the down
      regulation of growth factor-stimulated Grb2 signalling.

PMID- 29575432
TI  - Efficacy of Percutaneous Posterior Tibial Nerve Stimulation for the Management of
      Fecal Incontinence in Multiple Sclerosis: A Pilot Study.
AB  - BACKGROUND: Fecal incontinence is a debilitating and highly prevalent problem
      among multiple sclerosis patients. Conservative therapies often fail to provide
      benefit. Posterior tibial nerve stimulation is a minimally invasive
      neuromodulatory therapy with proven efficacy for fecal incontinence in non
      neurological settings. OBJECTIVE: To evaluate the efficacy of posterior tibial
      nerve stimulation in treating multiple sclerosis-related fecal incontinence.
      METHODS: Consecutive multiple sclerosis patients with fecal incontinence that had
      failed conservative therapy received posterior tibial nerve stimulation between
      2012 and 2015. All patients had previously undergone anorectal physiology tests
      and endoanal ultrasound. Patients whose Wexner incontinence score reduced below
      10 post-therapy or halved from baseline were deemed responders. RESULTS: Thirty
      three patients (25 female, median age 43 years) were included. Twenty-three (70%)
      had urge, 4 (12%) passive, and 9 (27%) mixed fecal incontinence. Twenty-six (79%)
      were classified as responders. The majority of subjects had relapsing-remitting
      multiple sclerosis (67%); those had a significantly higher response rate (95% vs.
      67% and 50% in primary and secondary progressive respectively, P < 0.05).
      Responders tended to be more symptomatic at baseline and had greater improvements
      in bowel symptom scores and quality of life scores with therapy. CONCLUSION:
      Posterior tibial nerve stimulation demonstrates potential as an effective therapy
      for fecal incontinence in multiple sclerosis. These findings provide the basis
      for future more definitive controlled studies.

PMID- 29575433
TI  - Gold(III) Complexes for Antitumor Applications: An Overview.
AB  - Gold(III) complexes have emerged as a versatile and effective class of metal
      based anticancer agents. The development of various types of ligands capable of
      stabilizing the AuIII cation and preventing its reduction under physiological
      conditions, such as chelating nitrogen-donors, dithiocarbamates and C^N
      cyclometalled ligands, has opened the way for the exploration of their potential
      intracellular targets and action mechanisms. At the same time, the bioconjugation
      of AuIII complexes has emerged as a promising strategy for improving the
      selectivity of this class of compounds for cancer cells over healthy tissues, and
      recent developments have shown that combining gold complexes with molecular
      structures that are specifically recognized by the cell can exploit the cell's
      own transport mechanisms to improve selective metal uptake.

PMID- 29575434
TI  - March 2018 at a glance: clinical trials, co-morbidities and treatment of mitral
      regurgitation.

PMID- 29575435
TI  - Implication of pulmonary hypertension in patients undergoing MitraClip therapy:
      results from the German transcatheter mitral valve interventions (TRAMI)
      registry.
AB  - AIMS: We sought to evaluate the impact of pulmonary hypertension on outcomes
      following MitraClip therapy. METHODS AND RESULTS: The 643 patients in the
      TRAnscatheter Mitral valve Interventions (TRAMI) registry were divided into three
      groups according to echocardiographically graded systolic pulmonary artery
      pressure (sPAP) (Group 1: patients with sPAP of <=36 mmHg; Group 2: patients with
      sPAP of 37-50 mmHg; Group 3: patients with sPAP of >50 mmHg) and followed for 1
      year. Recent cardiac decompensation, aortic valve disease and tricuspid valve
      insufficiency were observed more frequently in patients with higher sPAP.
      Furthermore, logEuroSCORE, Society of Thoracic Surgeons score and age were higher
      with rising sPAP values. No differences were observed in mitral regurgitation
      (MR) severity, co-morbidities or clinical findings (New York Heart Association
      class, 6-min walking distance). Reduction to MR of grade 1 or lower was achieved
      more often in patients with lower sPAP levels (P = 0.01). In Groups 2 and 3, sPAP
      was reduced significantly. Major adverse cardiac or cardiovascular events
      (MACCEs) occurring in hospital (death, myocardial infarction, stroke; <4% in each
      group), as well as 30-day rates of MACCEs (6.1% in Group 1, 11.9% in Group 2,
      12.4% in Group 3) and rehospitalization (18.9% in Group 1, 24.8% in Group 2,
      24.8% in Group 3) did not differ significantly. At 1 year, differences in rates
      of mortality and MACCEs (20.3% in Group 1, 33.1% in Group 2, 34.7% in Group 3; P
      < 0.01) were significant. Both Groups 2 [hazard ratio (HR) 1.81, P = 0.0122] and
      3 (HR 1.85, P = 0.0092) were independently predictive of death. Rehospitalization
      rates did not differ during follow-up. CONCLUSIONS: Despite higher mortality in
      patients with elevated sPAP, these data suggest the safety, feasibility and
      benefit of MitraClip therapy even in advanced stages of disease. An early
      approach might prevent the progress of pulmonary hypertension and improve
      outcomes.

PMID- 29575436
TI  - Letter from Taiwan.

PMID- 29575437
TI  - Meal composition influences postprandial sensations independently of valence and
      gustation.
AB  - BACKGROUND: Palatability of meals with identical composition has been shown to
      influence postprandial sensations. Our aim was to determine to what extent meal
      composition influences postprandial sensations independently of palatability.
      METHODS: Randomized, crossover, double-blind trial comparing the postprandial
      responses to a low-fat vs a high-fat test meal, with the same physical and
      organoleptic characteristics (taste, smell, texture, color, and temperature). The
      test meal consisted in 150 g hummus containing either 17.7 g fat (low-fat) or
      22.3 g fat (high-fat), 19.8 g toasts, 120 mL water and 50 g apple puree. In 12
      non-obese healthy men, palatability, homeostatic sensations (hunger/satiety,
      fullness) and hedonic sensations (digestive well-being, mood) were measured on 10
      cm scales before and during the 60-min postprandial period. Comparisons between
      meals were performed with a two-way repeated measures ANCOVA with premeal data as
      co-variate. KEY RESULTS: Both test meals were rated equally palatable
      (palatability scores 3.8 +/- 0.3 low-fat, 3.3 +/- 0.2 high-fat; P = .156). As
      compared to the high-fat meal, the low-fat meal induced more satisfaction (meal
      effect on well-being F(1,21) = 4.92; P = .038) and tended to improve mood (meal
      effect F(1,21) = 3.02; P = .064), and this was associated with a non-significant
      decrease in satiety (meal effect F(1,21) = 2.29; P = .145) and fullness (meal
      effect F(1,21) = 1.57; P = .224). CONCLUSIONS AND INFERENCES: The composition of
      meals with equal palatability influences postprandial satisfaction, even without
      significant impact on homeostatic sensations, although an effect on homeostatic
      sensations has not been excluded. These conditioning factors may have clinical
      implications in patients with impaired meal tolerance or meal-related symptoms.

PMID- 29575439
TI  - Urinary cytology and the Paris system for reporting urinary cytology:
      Implications for urological management.
AB  - By reducing the rate of indeterminate (atypical) diagnoses and standardising
      reporting terminology, The Paris System for Reporting Urine Cytology helps focus
      the application of cytology towards the detection primarily of high-grade
      urothelial carcinoma. We present a urology-based perspective of how the new
      system has influenced clinical decision-making.

PMID- 29575440
TI  - Facile One-Step Assembly of Bona Fide SUMO Conjugates by Chemoenzymatic Ligation.
AB  - The post-translational conjugation of the small ubiquitin-like modifiers (SUMOs)
      to target proteins occurs through a complex machinery that involves sequential
      action of at least three enzymes. SUMOylation performs crucial regulatory
      functions in several cellular processes. The availability of well-defined SUMO
      conjugates is necessary for untangling the mechanism of SUMOylation. However,
      assembly of homogeneous SUMO conjugates represents a challenge because of the
      multi-step synthesis involved and the unwieldiness of the reconstituted
      biosynthetic systems. Here we describe a simple one-step chemoenzymatic strategy
      for conjugating engineered SUMO (eSUMO) proteins to a prefabricated isopeptide
      linked SUMO target peptide. Notably, the eSUMOs were efficiently recognized by
      the enzymes of the SUMOylation machinery and the SUMO conjugates served as bona
      fide substrates for DeSUMOylating enzymes.

PMID- 29575438
TI  - Anti-epidermal growth factor receptor therapy concurrently with induction
      chemotherapy in locoregionally advanced nasopharyngeal carcinoma.
AB  - Little is known about the efficacy and toxicity of anti-epidermal growth factor
      receptor therapy concurrently with induction chemotherapy (IC) in locoregionally
      advanced nasopharyngeal carcinoma (LA-NPC). The present study aimed to address
      this question. We identified 2848 patients with newly diagnosed LA-NPC receiving
      IC between January 2012 and May 2015. The propensity score matching (PSM) method
      was used to balance various factors and to match patients. Survival outcomes and
      toxicities between different groups were compared. In total, 596 patients were
      selected at a 1:3 ratio, with 149 in the IC + CTX/NTZ group and 447 in the IC
      alone group. The 3-year disease-free survival, overall survival, distant
      metastasis-free survival and locoregional relapse-free survival rates for IC +
      CTX/NTZ vs IC alone were 84.3% vs 75.2% (P = .059), 94.0% vs 87.9% (P = .053),
      88.0% vs 84.9% (P = .412) and 93.3% vs 88.2% (P = .242). Multivariate analysis
      established a treatment group (IC vs IC + CTX/NTZ) as a prognostic predictor for
      DFS (hazard ratio [HR], 1.497; 95% confidence interval [CI], 1.016-2.206; P =
      .041) and OS (HR, 1.984; 95%, CI, 1.023-3.848; P = .043). Grade 3-4 skin reaction
      (15.4% vs 0.4%, P < .001) and mucositis (10.1% vs 2.7%, P < .001) were more
      common in the IC + CTX/NTZ group than that in the IC alone group. Our findings
      suggested that CTX/NTZ in combination with IC may be a more effective and
      promising strategy for patients with LA-NPC treated with intensity-modulated
      radiotherapy.

PMID- 29575441
TI  - Lactobacillus plantarum MTCC 9510 supplementation protects from chronic
      unpredictable and sleep deprivation-induced behaviour, biochemical and selected
      gut microbial aberrations in mice.
AB  - AIM: Here, we evaluated any beneficial effects of a potential probiotic bacterial
      strain (Lactobacillus plantarum MTCC 9510) in two different stress paradigms in
      mice. METHODS AND RESULTS: Lactobacillus plantarum MTCC 9510 (2 * 1010 CFU per
      mice) was supplemented to male Swiss albino mice either subjected to chronic
      unpredictable mild stress or sleep deprivation (SD) stress. Various behavioural
      and biochemical tests along with selected gut bacterial abundances were
      determined. Lactobacillus plantarum MTCC 9510 supplementation prevented stress
      induced behavioural despair (depression, anxiety, learning and memory,
      stereotypic behaviour), oxidative stress markers and inflammatory cytokines in
      brain and serum. Its supplementation also improved gut and blood brain barrier
      integrity. It also affected caecal short-chain fatty acids along with the
      promotion of Lactobacillus sp. and reduction in Enterobacteriaceae abundances. We
      also observed that two different stresses variably affected various behavioural
      and biochemical changes but L. plantarum MTCC 9510 supplementation most
      effectively prevented all these changes. CONCLUSION: We provide evidence that
      positive modulation of the selected beneficial gut microbial population could
      serve as a viable strategy to neutralize day-to-day and SD stress-induced
      pathological alterations. SIGNIFICANCE AND IMPACT OF THE STUDY: Therapeutic
      potential of this/other probiotic strains in tackling the deleterious
      neurobiological effects on exposure to various stress-related conditions can be
      explored.

PMID- 29575443
TI  - A lesion categorized between ghost cell odontogenic carcinoma and dentinogenic
      ghost cell tumor with CTNNB1 mutation.
AB  - Ghost cell odontogenic carcinoma (GCOC) is a rare malignant neoplasm
      characterized by the presence of ghost cells. It is considered to arise either de
      novo or from a preexisting benign precursor, calcifying odontogenic cyst (COC),
      or dentinogenic ghost cell tumor (DGCT). We report a case of a 44-year-old
      Japanese male with a left maxillary tumor. The patient received treatment to
      resect the left maxillary cyst 25 years prior; however, the details were
      uncertain. The tumor was resected with clear margins. Taken together with the
      results of histological and immunohistochemical examinations, the tumor was
      categorized between GCOC and DGCT, and we diagnosed the tumor as GCOC suggesting
      similarity to DGCT. Further, we focused on CTNNB1, which encodes beta-catenin and
      is frequently mutated in COCs. In this tumor, we identified CTNNB1 Ser33Cys, one
      of the mutations typically found in COCs. This finding suggests that CTNNB1 is a
      common target for the pathogenesis of tumors accompanied by ghost cells.

PMID- 29575442
TI  - High temporal resolution gastric emptying breath tests in mice.
AB  - BACKGROUND: Gastric emptying is a complex physiological process regulating the
      division of a meal into smaller partitions for the small intestine. Disrupted
      gastric emptying contributes to digestive disease, yet current measures may not
      reflect different mechanisms by which the process can be altered. METHODS: We
      have developed high temporal resolution solid and liquid gastric emptying breath
      tests in mice using [13 C]-octanoic acid and off axis- integrated cavity output
      spectroscopy (OA-ICOS). Stretched gamma variate and 2-component stretched gamma
      variate models fit measured breath excretion data. KEY RESULTS: These assays
      detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or
      physiological (nutrients, cold exposure stress, diabetes) manipulations and
      remain stable over time. High temporal resolution resolved complex excretion
      curves with 2 components, which was more prevalent in mice with delayed gastric
      emptying following streptozotocin-induced diabetes. There were differences in the
      gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a
      greater occurrence of two-phase gastric emptying curves in the latter strain.
      Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but
      with no effect on the occurrence of two-phase gastric emptying curves. A greater
      proportion of two-phase gastric emptying was induced in Balb/c mice with the
      administration of PYY (8-80 nmol) 60 min following meal ingestion. CONCLUSIONS
      AND INFERENCES: Collectively, these results demonstrate the utility of high
      temporal resolution gastric emptying assays. Two-phase gastric emptying is more
      prevalent than previously reported, likely involves intestinal feedback, but
      contributes little to the overall rate of gastric emptying.

PMID- 29575444
TI  - Safe and Facile Access to Nonstabilized Diazoalkanes Using Continuous Flow
      Technology.
AB  - Despite the high synthetic potential of nonstabilized diazo compounds, their
      utilization has always been hampered by stability, toxicity, and safety issues.
      The present method opens up access to the most reactive nonstabilized
      diazoalkanes. Among diazo compounds, nonstabilized alkyl diazo compounds are the
      least represented because of their propensity to degrade during preparation. The
      continuous flow oxidation process of hydrazones on a silver oxide column afforded
      an output stream of base- and metal-free pure diazo solution in dichloromethane.
      Starting from innocuous ketones and aldehydes, this methodology allows the
      production of a broad range of unprecedented diazoalkanes compounds in excellent
      yields, while highlighting their synthetic potential and the possibility of safe
      large-scale diazo production.

PMID- 29575445
TI  - Length-Dependent Manifestation of Vibration Modes Regulates a Specific
      Intermediate Morphology of Abeta17-42 in Different Environments.
AB  - Various cytotoxic mechanisms for neurodegenerative disease are induced by
      specific conformations of Abeta intermediates. The efforts to understand the
      diverse intermediate forms of amyloid oligomers have been focused on
      understanding the aggregation mechanism of specific morphologies for Abeta
      intermediates. However, these are still not easy tasks to be accomplished because
      the diverse conformations of Abeta intermediates can be altered during the
      aggregation process, even though the same Abeta monomers are present. Thus,
      efforts to reveal the conformational change mechanism could be a fundamental
      process to understand the formation of diverse Abeta intermediate conformations.
      Here, we evaluate the conformational characteristics of Abeta17-42 fibrillar
      oligomers in different environments according to the length. We observed that
      Abeta fibrillar oligomers optimize their inherent hydrogen bonds and
      configurational entropy to stabilize their structure according to the simulation
      time and their length increase. In addition, we revealed the role of the
      expressed vibration mode shape in the fibrillar oligomers' elongation and
      deformation processes. Our results suggest that limitations in amyloid oligomer
      growth and transformations of their morphologies can be regulated and controlled
      by modifying the vibration features.

PMID- 29575447
TI  - Relations of mindfulness facets with psychological symptoms among individuals
      with a diagnosis of obsessive-compulsive disorder, major depressive disorder, or
      borderline personality disorder.
AB  - OBJECTIVES: To explore differences in mindfulness facets among patients with a
      diagnosis of either obsessive-compulsive disorder (OCD), major depressive
      disorder (MDD), or borderline personality disorder (BPD), and healthy controls
      (HC), and their associations with clinical features. DESIGN AND METHOD: One
      hundred and fifty-three patients and 50 HC underwent a clinical assessment
      including measures of mindfulness (Five Facets Mindfulness Questionnaire - FFMQ),
      psychopathological symptoms (Symptom Check List-90-R), dissociation (Dissociative
      Experience Scale), alexithymia (Alexithymia Scale 20), and depression (Beck
      Depression Inventory-II). Analysis of variance (ANOVA) and analysis of covariance
      (ANCOVA) were performed to assess differences in mindfulness scores and their
      associations with clinical features. RESULTS: The three diagnostic groups scored
      lower on all mindfulness facets (apart from FFMQobserving) compared to the HC
      group. OCD group had a significant higher FFMQ total score (FFMQ-TS) and
      FFMQacting with awareness compared to the BPD group, and scored higher on
      FFMQdescribing compared to BPD and MDD groups. The scores in non-judging facet
      were significantly lower in all the three diagnostic groups compared to the HC
      group. Interestingly, higher FFMQ-TS was inversely related to all psychological
      measures, regardless of diagnostic group. CONCLUSIONS: Deficits in mindfulness
      skills were present in all diagnostic groups. Furthermore, we found disease
      specific relationships between some mindfulness facets and specific psychological
      variables. Clinical implications are discussed. PRACTITIONER POINTS: The study
      showed deficits in mindfulness scores in all diagnostic groups compared to a
      healthy control group. Overall, mindfulness construct has a significantly
      negative association with indexes of global distress, dissociative symptoms,
      alexithymia, and depression. Mindfulness-based interventions in clinical settings
      should take into account different patterns of mindfulness skills and their
      impact on disease-specific maladaptive cognitive strategies or symptomatology.

PMID- 29575446
TI  - Medication safety challenges in primary care: Nurses' perspective.
AB  - AIMS AND OBJECTIVES: To identify the issues surrounding medication error
      reporting in community nursing and improvement strategies related to medication
      safety. BACKGROUND: Medication-related problems have been identified from various
      sources in the literature. Examples of these include incident reporting by
      healthcare professionals, medico-legal and patient complaints and systematic
      identification of organisational structure. Only a few studies report on the
      clinicians' perceptions of medication safety in community nursing and the
      challenges they face within their workplace to implement medication safety
      initiatives. DESIGN: Qualitative design, using conversation-style interviews with
      experienced registered nurses in primary care roles. METHODS: Using a general
      iterative approach of semantic analysis, our qualitative research study was
      guided by an essentialist paradigm. Our method for understanding included semi
      structured in-depth interviews with 10 clinicians from a large community care
      organisation in rural Victoria in Australia. We developed an interview guide,
      which included open-ended questions on clinicians' experiences, perceived
      barriers and facilitators, and strategies to improve medication safety. RESULTS:
      Several barriers have been identified by healthcare practitioners that hinder
      medication safety in primary care including culture differences between community
      and hospital setting, politics within the healthcare system, lack of clarity
      around the nurses' roles and lack of error reporting. Other sources of errors
      cited by the participants were the lack of clarity or awareness of the processes
      and procedures of medication incidents reporting for staff within the
      organisation experience. Lack of education regarding medication safety, the
      dilemmas associated with reporting and documentation are also significant
      barriers.

PMID- 29575448
TI  - Comparison of closely related, uncultivated Coxiella tick endosymbiont population
      genomes reveals clues about the mechanisms of symbiosis.
AB  - Understanding the symbiotic interaction between Coxiella-like endosymbionts (CLE)
      and their tick hosts is challenging due to lack of isolates and difficulties in
      tick functional assays. Here we sequenced the metagenome of a CLE population from
      wild Rhipicephalus sanguineus ticks (CRs) and compared it to the previously
      published genome of its close relative, CLE of R. turanicus (CRt). The tick hosts
      are closely related sympatric species, and their two endosymbiont genomes are
      highly similar with only minor differences in gene content. Both genomes encode
      numerous pseudogenes, consistent with an ongoing genome reduction process. In
      silico flux balance metabolic analysis (FBA) revealed the excess production of L
      proline for both genomes, indicating a possible proline transport from Coxiella
      to the tick. Additionally, both CR genomes encode multiple copies of the
      proline/betaine transporter, proP gene. Modelling additional Coxiellaceae members
      including other tick CLE, did not identify proline as an excreted metabolite.
      Although both CRs and CRt genomes encode intact B vitamin synthesis pathway
      genes, which are presumed to underlay the mechanism of CLE-tick symbiosis, the
      FBA analysis indicated no changes for their products. Therefore, this study
      provides new testable hypotheses for the symbiosis mechanism and a better
      understanding of CLE genome evolution and diversity.

PMID- 29575449
TI  - Population and evolutionary dynamics in spatially structured seasonally varying
      environments.
AB  - Increasingly imperative objectives in ecology are to understand and forecast
      population dynamic and evolutionary responses to seasonal environmental variation
      and change. Such population and evolutionary dynamics result from immediate and
      lagged responses of all key life-history traits, and resulting demographic rates
      that affect population growth rate, to seasonal environmental conditions and
      population density. However, existing population dynamic and eco-evolutionary
      theory and models have not yet fully encompassed within-individual and among
      individual variation, covariation, structure and heterogeneity, and ongoing
      evolution, in a critical life-history trait that allows individuals to respond to
      seasonal environmental conditions: seasonal migration. Meanwhile, empirical
      studies aided by new animal-tracking technologies are increasingly demonstrating
      substantial within-population variation in the occurrence and form of migration
      versus year-round residence, generating diverse forms of 'partial migration'
      spanning diverse species, habitats and spatial scales. Such partially migratory
      systems form a continuum between the extreme scenarios of full migration and full
      year-round residence, and are commonplace in nature. Here, we first review basic
      scenarios of partial migration and associated models designed to identify
      conditions that facilitate the maintenance of migratory polymorphism. We
      highlight that such models have been fundamental to the development of partial
      migration theory, but are spatially and demographically simplistic compared to
      the rich bodies of population dynamic theory and models that consider spatially
      structured populations with dispersal but no migration, or consider populations
      experiencing strong seasonality and full obligate migration. Second, to provide
      an overarching conceptual framework for spatio-temporal population dynamics, we
      define a 'partially migratory meta-population' system as a spatially structured
      set of locations that can be occupied by different sets of resident and migrant
      individuals in different seasons, and where locations that can support
      reproduction can also be linked by dispersal. We outline key forms of within
      individual and among-individual variation and structure in migration that could
      arise within such systems and interact with variation in individual survival,
      reproduction and dispersal to create complex population dynamics and evolutionary
      responses across locations, seasons, years and generations. Third, we review
      approaches by which population dynamic and eco-evolutionary models could be
      developed to test hypotheses regarding the dynamics and persistence of partially
      migratory meta-populations given diverse forms of seasonal environmental
      variation and change, and to forecast system-specific dynamics. To demonstrate
      one such approach, we use an evolutionary individual-based model to illustrate
      that multiple forms of partial migration can readily co-exist in a simple
      spatially structured landscape. Finally, we summarise recent empirical studies
      that demonstrate key components of demographic structure in partial migration,
      and demonstrate diverse associations with reproduction and survival. We thereby
      identify key theoretical and empirical knowledge gaps that remain, and consider
      multiple complementary approaches by which these gaps can be filled in order to
      elucidate population dynamic and eco-evolutionary responses to spatio-temporal
      seasonal environmental variation and change.

PMID- 29575450
TI  - Influence of room temperature on magnesium isotope measurements by multi
      collector inductively coupled plasma mass spectrometry.
AB  - RATIONALE: We observed that the accuracy and precision of magnesium (Mg) isotope
      analyses could be affected if the room temperature oscillated during
      measurements. To achieve high-quality Mg isotopic data, it is critical to
      evaluate how the unstable room temperature affects Mg isotope measurements by
      multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS).
      METHODS: We measured the Mg isotopes for the reference material DSM-3 using MC
      ICP-MS under oscillating room temperatures in spring. For a comparison, we also
      measured the Mg isotopes under stable room temperatures, which were achieved by
      the installation of an improved temperature control system in the laboratory.
      RESULTS: The delta26 Mg values measured under oscillating room temperatures have
      a larger deviation (delta26 Mg from -0.09 to 0.080/00, with average delta26 Mg =
      0.00 +/- 0.080/00) than those measured under a stable room temperature (delta26
      Mg from -0.03 to 0.030/00, with average delta26 Mg = 0.00 +/- 0.020/00) using the
      same MC-ICP-MS system. CONCLUSIONS: The room temperature variation can influence
      the stability of MC-ICP-MS. Therefore, it is critical to keep the room
      temperature stable to acquire high-precision and accurate isotopic data when
      using MC-ICP-MS, especially when using the sample-standard bracketing (SSB)
      correction method.

PMID- 29575451
TI  - Corrigendum: Zekri W, Alfaar AS, Yehia D, et al. Clear cell sarcoma of the
      kidney: Patients' characteristics and improved outcome in developing countries.
      Pediatr Blood Cancer. 2014;61:2185-2190. DOI: 10.1002/pbc.25192.

PMID- 29575453
TI  - Inhibition of alpha-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends.
AB  - Misfolding of the protein alpha-synuclein (alphaSyn) into amyloid fibrils plays a
      central role in the development of Parkinson's disease. Most approaches for the
      inhibition of alphaSyn fibril formation are based on stabilizing the native
      monomeric form of the protein or destabilizing the fibrillized misfolded form.
      They require high concentrations of inhibitor and therefore cannot be easily used
      for therapies. In this work, we designed an inhibitor (Inh-beta) that selectively
      binds the growing ends of alphaSyn fibrils and creates steric hindrance for the
      binding of monomeric alphaSyn. This approach permits the inhibition of fibril
      formation at Inh-beta concentrations (IC50 =850 nm) much lower than the
      concentration of monomeric alphaSyn. We studied its kinetic mechanism in vitro
      and identified the reactions that limit inhibition efficiency. It is shown that
      blocking of alphaSyn fibril ends is an effective approach to inhibiting fibril
      growth and provides insights for the development of effective inhibitors of
      alphaSyn aggregation.

PMID- 29575452
TI  - Bioactivity of novel functionally structured titanium-ceramic composites in
      contact with human osteoblasts.
AB  - The aim of this study was to analyze the osteogenic cell behavior on the surface
      of novel functionally graded titanium-based composites containing bioactive
      ceramics. Titanium grade V discs (8 * 3 mm) embedding gradual content of
      hydroxyapatite (TiAlV-HA) or beta-tricalcium phosphate (TiAlV-betaTCP) were
      produced by hot-pressing technique. Titanium-ceramic composite discs and Ti grade
      V (control group) were placed in contact with human osteoblast culture assays.
      The morphology and adhesion of osteoblasts were inspected by field emission guns
      scanning electron microscopy (FEGSEM) while cell viability was assessed by
      fluorometric method. Alkaline phosphatase (ALP) activity and fluorescent
      microscopic analyses were used to evaluate mineralization on the test and control
      discs. FEGSEM images showed cells adhered to Ti6Al4V-ceramic and Ti6Al4V surfaces
      over a period of 24 h, and therefore, an intense proliferation of osteoblasts and
      spreading cells was noticed for 7 days. Cell viability increased with time on all
      the surfaces although TiAlV-betaTCP revealed significant higher percentage of
      cell viability than that recorded for TiAlV-HA (p < 0.01). TiAlV-betaTCP also
      showed the highest hydrophilic character. ALP levels increased on the Ti6Al4V
      ceramic surfaces when compared to the control group. Also, a qualitative analysis
      of mineralization evidenced an increase in mineral content on TiAlV-HA or TiAlV
      betaTCP groups. Novel functionally graded composites based on Ti grade V and
      hydroxyapatite or betaTCP showed a higher bioactivity in presence of osteoblasts
      than that recorded on Ti grade V. Also, such functionally graded materials can
      prevent risks of failures by detachment of bioactive ceramic materials during
      implant placement. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 1923-1931, 2018.

PMID- 29575454
TI  - Different perception of chronic constipation between patients and
      gastroenterologists.
AB  - BACKGROUND: There is a certain number of subjects that consider themselves to be
      constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC
      from IBS-C, but some SDC patients do not meet the Rome criteria (no Rome
      Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with
      a diagnosis of FC and IBS-C and to compare demographic and clinical features,
      symptoms, and quality of life in the different SDC groups (FC, IBS-C, NRC).
      METHODS: During a 2-month period, 934 patients and 980 accompanying persons (AP)
      were asked to complete a survey. The presence of FC or IBS-C was assessed. SDC
      subjects were invited to record the stool consistency (Bristol scale) and to fill
      in the Constipation Severity Index (CSI), obstructed defecation syndrome (ODS)
      and patient assessment of constipation-quality of life (PAC-QoL). The use of
      laxatives and enemas was evaluated. KEY RESULTS: The probability of the ROME III
      criteria being present was higher in SDC compared with no-SDC (OR 20.5). NRC was
      present in 13.5% of the SDC. In the patients' group the agreement between a
      diagnosis of Rome III and SDC was good (K 0.62), whereas in the AP it was
      moderate (K 0.56). NRC showed lower mean values of ODS, CSI and PAC-QoL, higher
      Bristol scale and a lower use of laxatives and enemas compared to IBS-C and FC.
      No differences were found between IBS-C and FC. CONCLUSIONS AND INFERENCES: The
      Rome III criteria identify subjects with a greater clinical impact, but
      separation of FC and IBS-C does not seem justified.

PMID- 29575455
TI  - Cephalosporin-resistant Escherichia coli isolated from farm workers and pigs in
      northern Vietnam.
AB  - OBJECTIVE: Antimicrobial-resistant bacteria may be transmitted between farm
      workers and livestock. This study aimed to determine and compare the prevalence
      and the genetic determinants of cefotaxime-resistant and ESBL-producing
      Escherichia coli in faecal isolates from workers and pigs at 100 farms in
      northern Vietnam. METHODS: Farmers were interviewed about antimicrobial usage in
      livestock. Escherichia coli isolated on MacConkey agar containing 2 mg/l of
      cefotaxime (CTX) were tested for susceptibility to different cephalosporins by
      disc diffusion and screened for occurrence of ESBL-encoding genes by PCR.
      RESULTS: Antimicrobial usage was widespread and included classes regarded of
      critical or high importance in human medicine. Dosages were 0.5-2 times higher
      than recommended, and antimicrobials were often administered right until
      slaughter. Prevalence of CTX-resistant E. coli was 86% in farm workers and 89% in
      pigs. In 76% of farms, CTX-resistant E. coli were shared by pigs and farm
      workers. ESBL-producing E. coli were detected from pigs and workers at 66 and 69
      farms, respectively. The ESBL phenotype was mainly mediated by CTX-M and to a
      lesser extent by TEM. Occurrence of blaCTX-M was similar in E. coli from pigs
      (66.7%) and humans (68.5%). CONCLUSION: The high occurrence of ESBL-producing E.
      coli in pig farmers and pigs could present a risk for spillover of these bacteria
      from pig farms into the community. Genomic studies are needed to elucidate
      reservoirs and transmission routes of ESBL-producing E. coli at livestock farms.

PMID- 29575456
TI  - Fat embolism syndrome in a child triggered by surgical tourniquet release: A case
      report.

PMID- 29575457
TI  - Pediatric perioperative outcomes group: Defining core outcomes for pediatric
      anesthesia and perioperative medicine.

PMID- 29575458
TI  - Third time's a charm: Oral midazolam vs intranasal dexmedetomidine for
      preoperative anxiolysis in an autistic pediatric patient.

PMID- 29575459
TI  - Parent and anesthetist attitudes toward rectal analgesic suppositories in
      pediatric daycase surgery: A multi-center cross-sectional survey.

PMID- 29575460
TI  - In this issue: April 2018.

PMID- 29575461
TI  - Custom-Made Ceria Nanoparticles Show a Neuroprotective Effect by Modulating
      Phenotypic Polarization of the Microglia.
AB  - The neuroprotective effect of ceria nanoparticles in the context of brain
      disorders has been explained by their antioxidant effect. However, the in-depth
      mechanism remains unknown. As resident immune cells in the brain, microglia exert
      a variety of functional reprogramming termed as polarization in response to
      stress stimuli. Herein, custom-made ceria nanoparticles were developed and found
      to scavenge multiple reactive oxygen species with extremely high efficiency.
      These nanoparticles drove microglial polarization from a pro-inflammatory
      phenotype to an anti-inflammatory phenotype under pathological conditions.
      Pretreatment of these nanoparticles changed the microglial function from
      detrimental to protective for the neuronal cells by blocking the pro-inflammatory
      signaling. This work not only helps to elucidate the mechanism of ceria
      nanoparticle-mediated neuroprotection but also provides a new strategy to
      rebalance the immuno-environment by switching the equilibrium of the phenotypic
      activation of microglia.

PMID- 29575462
TI  - The challenge of the biosciences in nurse education: A literature review.
AB  - AIMS AND OBJECTIVES: To review relevant literature that addresses the challenges
      of the biosciences in nurse education. More precisely, the review aims to explore
      the literature, concerning students' learning, learning contexts and
      methodological issues and identify any significant gaps. BACKGROUND: Knowledge of
      anatomy, physiology and biochemistry is essential for the understanding of human
      beings and for full appreciation of the concepts of illness and disease. The
      current status would seem to be that the required competencies within bioscience
      subjects are difficult to acquire and students have high rates of failure.
      DESIGN: Integrative review. METHODS: The research was performed on CINAHL, ERIC,
      Medline and British Nursing Index databases in a period from 2013-2017.
      Descriptive analytical methods were used for the initial research trawl.
      FINDINGS: The search strategy resulted in 23 papers. The results of this review
      shed light on certain deficiencies in the research field looking at the
      biosciences in nurse education. There is a distinct lack of intervention studies
      and, thereby, knowledge of how best to support students' learning in effective
      ways. Of note is that there are no field study approaches identified in the
      review sample. CONCLUSION: Many of the papers are single studies and course
      evaluations which may be seen as too narrow and inadequate as perspective.
      Students appear satisfied with the courses in the biosciences, but there seems to
      be no correlation between satisfaction and achievement. RELEVANCE TO CLINICAL
      PRACTICE: Understanding and being able to give coherent rationales for the
      bioscience content in the nursing curricula are crucial and must be established
      in relation to its relevance to the dynamic nature of patient care, technological
      advances and demographic realities. Only on that basis can the primacy of this
      content be seen as relevant to the aspiring student nurse.

PMID- 29575463
TI  - Environmental microbiology to the rescue of planet earth.
AB  - Environmental Microbiology has undergone a dramatic transition from being a
      somewhat marginal branch of Life Sciences to becoming one of the most vibrant and
      visible areas of contemporary research. The homonymous journal has not only borne
      witness of the growing interest in environmental microbes that bloomed since the
      mid-1980s but it has helped also to give visibility to the field and nucleate an
      active and influential community of authors and readers. During the past 20 years
      the focus has shifted from individual isolates to communities and microbiomes,
      from single genomes to metagenomes and from small/medium-scale experimental
      systems to large/very large scenarios. New challenges that were somewhat marginal
      when the journal was founded have acquired an unanticipated relevance owing to
      their impact on the global Earth's homeostasis. They include the unacceptably
      high atmospheric levels of greenhouse gases, the worrying pollution of the oceans
      with very recalcitrant plastics and microplastics and the noxious effects of
      micropollutants on many ecosystems. Global problems ask for global solutions and
      the environmental microbiome - because of its dimension and its amazing
      activities - may end up being out best instrument to both counter the impact of
      industrial development and enable a new, sustainable partnership with Nature.

PMID- 29575464
TI  - Tumor necrosis factor-alpha induces prostate cancer cell migration in lymphatic
      metastasis through CCR7 upregulation.
AB  - Understanding the mechanism of lymph node metastasis, a poor prognostic sign for
      prostate cancer, and the further dissemination of the disease is important to
      develop novel treatment strategies. Recent studies have reported that C-C
      chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in
      lymph node metastasis and promotes cancer progression. Tumor necrosis factor
      alpha (TNF-alpha) is chronically produced at low levels within the tumor
      microenvironment. The aim of this study was to determine whether TNF-alpha
      promotes prostate cancer dissemination from metastatic lymph nodes through
      activation of the CCL21/CCR7 axis. First, human prostate cancer cells were
      determined to express both TNF-alpha and CCR7. Second, low concentrations of TNF
      alpha were confirmed to induce CCR7 in prostate cancer cells through
      phosphorylation of ERK. Finally, CCL21 was found to promote the migration of
      prostate cancer cells through phosphorylation of the protein kinase p38. Our
      results suggest that TNF-alpha leads to the induction of CCR7 expression and that
      the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer
      cells in lymph node metastasis.

PMID- 29575465
TI  - Reversible Switching between Highly Porous and Nonporous Phases of an
      Interpenetrated Diamondoid Coordination Network That Exhibits Gate-Opening at
      Methane Storage Pressures.
AB  - Herein, we report that a new flexible coordination network, NiL2 (L=4-(4-pyridyl)
      biphenyl-4-carboxylic acid), with diamondoid topology switches between non-porous
      (closed) and several porous (open) phases at specific CO2 and CH4 pressures.
      These phases are manifested by multi-step low-pressure isotherms for CO2 or a
      single-step high-pressure isotherm for CH4 . The potential methane working
      capacity of NiL2 approaches that of compressed natural gas but at much lower
      pressures. The guest-induced phase transitions of NiL2 were studied by single
      crystal XRD, in situ variable pressure powder XRD, synchrotron powder XRD,
      pressure-gradient differential scanning calorimetry (P-DSC), and molecular
      modeling. The detailed structural information provides insight into the extreme
      flexibility of NiL2 . Specifically, the extended linker ligand, L, undergoes
      ligand contortion and interactions between interpenetrated networks or sorbate
      sorbent interactions enable the observed switching.

PMID- 29575466
TI  - Post-transplantation lymphoproliferative disease in pediatric kidney transplant
      recipients-early success does not mean the battle is over!

PMID- 29575467
TI  - Microporous Polycarbazole Materials: From Preparation and Properties to
      Applications.
AB  - Polycarbazoles with rigid skeletons and electron-rich conjugated systems are
      beneficial to form permanent porous materials with intrinsic photoelectric
      properties. In recent years, the research related to porous polycarbazoles
      becomes a hot topic in the field of porous organic polymers. The preparation
      methods for porous polycarbazoles are diverse, commonly represented by the
      oxidation coupling reaction and the Friedel-Crafts reaction. Other methods such
      as nitrile-based trimerization, electrochemical polymerization, and classic C-C
      coupling reactions are also reported. Porous polycarbazoles generally possess
      large specific surface area, permanent pore structure, and high thermal and
      chemical stability, which show potential applications in gas storage and
      separation, catalysis, sensors, and electronics. In this review, the recent
      research progress on the synthetic methods, functions, and applications of porous
      polycarbazoles is summarized.

PMID- 29575468
TI  - Corrigendum: A Tandem Green-Red Heterodimeric Fluorescent Protein with High FRET
      Efficiency.

PMID- 29575469
TI  - The effects of graded caloric restriction: XII. Comparison of mouse to human
      impact on cellular senescence in the colon.
AB  - Calorie restriction (CR) is an effective strategy to delay the onset and
      progression of aging phenotypes in a variety of organisms. Several molecular
      players are involved in the anti-aging effects of CR, but mechanisms of
      regulation are poorly understood. Cellular senescence-a cellular state of
      irreversible growth arrest-is considered a basic mechanism of aging. Senescent
      cells accumulate with age and promote a number of age-related pathologies.
      Whether environmental conditions such as diet affect the accumulation of cellular
      senescence with age is still unclear. Here, we show that a number of classical
      transcriptomic markers of senescent cells are reduced in adult but relatively
      young mice under CR. Moreover, we demonstrate that such senescence markers are
      not induced in the colon of middle-age human volunteers under CR in comparison
      with age-matched volunteers consuming normal Western diets. Our data support the
      idea that the improvement in health span observed in different organisms under CR
      might be partly due to a reduction in the number of senescent cells.

PMID- 29575470
TI  - Mechanism of bisphenol AF-induced progesterone inhibition in human chorionic
      gonadotrophin-stimulated mouse Leydig tumor cell line (mLTC-1) cells.
AB  - Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male
      rats. However, the precise mechanisms related to the toxic effects of BPAF on
      reproduction remain poorly understood. In the present study, a mouse Leydig tumor
      cell line (mLTC-1) was used as a model to investigate the mechanism of
      steroidogenic inhibition and to identify the molecular target of BPAF. Levels of
      progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in
      cells exposed to BPAF were detected, and expression of key genes and proteins in
      steroid biosynthesis was assessed. The results showed that BPAF exposure
      decreased human chorionic gonadotrophin (hCG)-stimulated progesterone production
      in a dose-dependent manner. The 24-h IC50 (half maximal inhibitory concentration)
      value for BPAF regarding progesterone production was 70.2 uM. A dramatic decrease
      in cellular cAMP concentration was also observed. Furthermore, BPAF exposure
      inhibited expression of genes and proteins involved in cholesterol transport and
      progesterone biosynthesis. Conversely, the protein levels of steroidogenic acute
      regulatory protein (StAR) were not altered, and those of progesterone were still
      decreased upon 22R-hydroxycholesterol treatment of cells exposed to higher doses
      of BPAF. Together, these data indicate that BPAF exposure inhibits progesterone
      secretion in hCG-stimulated mLTC-1 cells by reducing expression of scavenger
      receptor class B type I (SR-B1) and cytochrome P450 (P450scc) due to the adverse
      effects of cAMP. However, StAR might not be the molecular target in this process.

PMID- 29575472
TI  - Placement of Single Proteins within the SERS Hot Spots of Self-Assembled Silver
      Nanolenses.
AB  - This study demonstrates the bottom-up synthesis of silver nanolenses. A robust
      coating protocol enabled the functionalization of differently sized silver
      nanoparticles with DNA single strands of orthogonal sequence. Coated particles 10
      nm, 20 nm, and 60 nm in diameter were self-assembled by DNA origami scaffolds to
      form silver nanolenses. Single molecules of the protein streptavidin were
      selectively placed in the gap of highest electric field enhancement. Streptavidin
      labelled with alkyne groups served as model analyte in surface-enhanced Raman
      scattering (SERS) experiments. By correlated Raman mapping and atomic force
      microscopy, SERS signals of the alkyne labels of a single streptavidin molecule,
      from a single silver nanolens, were detected. The discrete, self-similar
      aggregates of solid silver nanoparticles are promising for plasmonic
      applications.

PMID- 29575471
TI  - Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home
      cage phenotyping.
AB  - Mouse models are widely used to understand genetic bases of behavior. Traditional
      testing typically requires multiple experimental settings, captures only
      snapshots of behavior and involves human intervention. The recent development of
      automated home cage monitoring offers an alternative method to study mouse
      behavior in their familiar and social environment, and over weeks. Here, we used
      the IntelliCage system to test this approach for mouse phenotyping, and studied
      mice lacking Gpr88 that have been extensively studied using standard testing. We
      monitored mouse behavior over 22 days in 4 different phases. In the free
      adaptation phase, Gpr88 -/- mice showed delayed habituation to the home cage, and
      increased frequency of same corner returns behavior in their alternation pattern.
      In the following nose-poke adaptation phase, non-habituation continued, however,
      mutant mice acquired nose-poke conditioning similar to controls. In the place
      learning and reversal phase, Gpr88-/- mice developed preference for the
      water/sucrose corner with some delay, but did not differ from controls for
      reversal. Finally, in a fixed schedule-drinking phase, control animals showed
      higher activity during the hour preceding water accessibility, and reduced
      activity after access to water was terminated. Mutant mice did not show this
      behavior, showing lack of anticipatory behavior. Our data therefore confirm
      hyperactivity, non-habituation and altered exploratory behaviors that were
      reported previously. Learning deficits described in other settings were barely
      detectable, and a novel phenotype was discovered. Home cage monitoring therefore
      extends previous findings and shows yet another facet of GPR88 function that
      deserves further investigation.

PMID- 29575473
TI  - Molecular Modeling Approach to Determine the Flory-Huggins Interaction Parameter
      for Polymer Miscibility Analysis.
AB  - In this work, we present a thorough procedure for estimating the Flory-Huggins
      chi-parameter for use in atomistic and mesoscale molecular simulations in
      computational materials science. In particular, we propose improvements upon
      traditional Flory-Huggins theory by implementing a Connolly volume normalization
      (CVN). We apply this technique to several test systems, including a blend of poly
      (epichlorohydrin) and poly (methyl acrylate), a blend of polyethylene glycol and
      poly (methyl methacrylate), a blend of polystyrene and deuterated polystyrene,
      and three molecular-weight variants (monomer, dimer, and trimer) of a triblock
      copolymer for use in multicompartment micelle applications. Our results
      demonstrate that the newly developed procedure offers high accuracy and
      efficiency in predicting the Flory-Huggins chi-parameter for miscibility analysis
      compared to traditional experimental and computational methods. There are still
      several factors that cause the magnitude of the chi-parameter to vary between
      simulations performed on molecular species with the same identity but different
      degrees of polymerization; although we discuss possible explanations for these
      factors, this is nonetheless a primary focus for further exploration into this
      new methodology.

PMID- 29575474
TI  - Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads.
AB  - Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has
      significant variability of severity. Preliminary studies have suggested that
      epigenetic variation within the MU-opioid receptor (OPRM1) gene impacts NAS. We
      aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother
      infant dyads is associated with differences in NAS severity in an independent
      cohort. Full-term opioid-exposed newborns and their mothers (N = 68 pairs) were
      studied. A DNA sample was obtained and then assessed for level of DNA methylation
      at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing.
      Infants were monitored for NAS and treated with replacement opioids according to
      institutional protocol. The association between DNA methylation level at each CpG
      site with NAS outcome measures was evaluated using linear and logistic regression
      models. Higher methylation levels within the infants at the -18 (11.4% vs 4.4%, P
      = .0001), -14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG
      sites were associated with higher rates of infant pharmacologic treatment. Higher
      levels of methylation within the mothers at the -169 (R = 0.43, P = .008), -152
      (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point
      wise with longer infant length of stay. Maternal associations remained
      significant point-wise for -169 (beta = 0.07, P = .007) and on an experiment-wise
      level for +84 (beta = -0.10, P = .003) using regression models. These results
      suggest an association of higher levels of OPRM1 methylation at specific CpG
      sites and increased NAS severity, replicating prior findings. These findings have
      important implications for personalized treatment regimens for infants at high
      risk for severe NAS.

PMID- 29575475
TI  - Synthesis of Reversed C-Acyl Glycosides through Ni/Photoredox Dual Catalysis.
AB  - The incorporation of C-glycosides in drug design has become a routine practice
      for medicinal chemists. These naturally occurring building blocks exhibit
      attractive pharmaceutical profiles, and have become an important target of
      synthetic efforts in recent decades. Described herein is a practical, scalable,
      and versatile route for the synthesis of non-anomeric and unexploited C-acyl
      glycosides through a Ni/photoredox dual catalytic system. By utilizing an organic
      photocatalyst, a range of glycosyl-based radicals are generated and efficiently
      coupled with highly functionalized carboxylic acids at room temperature.
      Distinctive features of this transformation include its mild conditions,
      impressive compatibility with a wide array of functional groups, and most
      significantly, preservation of the anomeric carbon: a handle for further, late
      stage derivatization.

PMID- 29575476
TI  - Quality of head and neck radiotherapy reporting in randomized controlled trials.
AB  - BACKGROUND: The purpose of this clinical review was to determine the quality
      reporting of radiotherapy (RT) in randomized controlled trials (RCTs) of head and
      neck cancer and its impact on reporting of the trial primary efficacy and
      toxicity outcomes. METHODS: We searched MEDLINE for eligible RCTs published
      between 1994 and 2015. We assessed the quality of RT reporting and bias in the
      reporting of trial outcomes using published criteria. RESULTS: We found 67
      eligible trial reports. There was significant variability in the quality of RT
      treatment reporting among the included trials. Thirty-two trials had adequate
      quality RT reporting. Cooperative group trials were more likely to have adequate
      quality reporting (odds ratio [OR] 3.02; 95% confidence interval [CI] 1.04-9.85).
      The quality of RT reporting did not influence the bias in the reporting of trial
      outcomes. CONCLUSION: The quality of head and neck RT reporting in RCTs is
      variable and did not impact on bias in reporting of trial outcomes.

PMID- 29575477
TI  - Ribosome display and selection of single-chain variable fragments effectively
      inhibit growth and progression of microspheres in vitro and in vivo.
AB  - Distinguishing the surface markers of cancer stem cells (CSCs) is a useful method
      for early diagnosis and treatment of tumors, as CSCs may participate in
      tumorigenesis and metastasis by migrating into the circulatory system. However,
      the potential targets of CSCs are expressed at low levels in the natural state
      and are always changing. Thus, dynamic screening has been reported to be an
      effective measure for exploring CSC markers. In recent years, diverse single
      chain variable fragments (scFvs) have been widely used in immunotherapy. In this
      study, we determined that the scFvs, screened using RD, had a high affinity to
      microspheres and could inhibit their progression. We also observed that the
      selected scFvs underwent evolution in vitro, and antitumor-associated proteins
      were successfully expressed. Combined with chemotherapy, the scFvs had a
      synergistic effect on the inhibition of the microspheres' progression in vitro
      and in vivo, which could be ascribed to their high affinity for stem-like cells
      and the inhibition of the microspheres' collective behaviors. In addition,
      proteins inhibiting CD44+ /CD24+ and MAPK were involved. Our data indicated that
      dynamic screening of the scFvs in a natural state was of great significance in
      the inhibition of the microspheres in vitro and in vivo.

PMID- 29575478
TI  - Vesicle Tubulation with Self-Assembling DNA Nanosprings.
AB  - A major goal of nanotechnology and bioengineering is to build artificial
      nanomachines capable of generating specific membrane curvatures on demand.
      Inspired by natural membrane-deforming proteins, we designed DNA-origami curls
      that polymerize into nanosprings and show their efficacy in vesicle deformation.
      DNA-coated membrane tubules emerge from spherical vesicles when DNA-origami
      polymerization or high membrane-surface coverage occurs. Unlike many previous
      methods, the DNA self-assembly-mediated membrane tubulation eliminates the need
      for detergents or top-down manipulation. The DNA-origami design and deformation
      conditions have substantial influence on the tubulation efficiency and tube
      morphology, underscoring the intricate interplay between lipid bilayers and
      vesicle-deforming DNA structures.

PMID- 29575479
TI  - Increasing autophagy and blocking Nrf2 suppress laminopathy-induced age-dependent
      cardiac dysfunction and shortened lifespan.
AB  - Mutations in the human LMNA gene cause a collection of diseases known as
      laminopathies. These include myocardial diseases that exhibit age-dependent
      penetrance of dysrhythmias and heart failure. The LMNA gene encodes A-type
      lamins, intermediate filaments that support nuclear structure and organize the
      genome. Mechanisms by which mutant lamins cause age-dependent heart defects are
      not well understood. To address this issue, we modeled human disease-causing
      mutations in the Drosophila melanogaster Lamin C gene and expressed mutant Lamin
      C exclusively in the heart. This resulted in progressive cardiac dysfunction,
      loss of adipose tissue homeostasis, and a shortened adult lifespan. Within
      cardiac cells, mutant Lamin C aggregated in the cytoplasm, the CncC(Nrf2)/Keap1
      redox sensing pathway was activated, mitochondria exhibited abnormal morphology,
      and the autophagy cargo receptor Ref2(P)/p62 was upregulated. Genetic analyses
      demonstrated that simultaneous over-expression of the autophagy kinase Atg1 gene
      and an RNAi against CncC eliminated the cytoplasmic protein aggregates, restored
      cardiac function, and lengthened lifespan. These data suggest that simultaneously
      increasing rates of autophagy and blocking the Nrf2/Keap1 pathway are a potential
      therapeutic strategy for cardiac laminopathies.

PMID- 29575480
TI  - Activation of PhoBR under phosphate-rich conditions reduces the virulence of
      Xanthomonas oryzae pv. oryzae.
AB  - The two-component signal transduction system PhoBR regulates the adaptation to
      phosphate limitation and the virulence of many animal bacterial pathogens.
      However, PhoBR in phytopathogens has rarely been investigated. In this study, we
      found that PhoBR in Xanthomonas oryzae pv. oryzae (Xoo), the pathogen of rice
      bacterial leaf blight, also regulates the adaptation to phosphate starvation.
      Unexpectedly, rice leaves infected by the phoBR-deleted mutant and wild-type
      PXO99A showed similar lesions, indicating that PhoBR is unnecessary for the
      virulence of Xoo. phoBR was found to be silenced during host infection, whereas
      artificially constitutive PhoBR expression attenuated virulence on host rice and
      growth in phosphate-rich media. RNA-sequencing (RNA-seq) was then performed to
      investigate the global effect caused by constitutive PhoBR activation. RNA-seq
      and further experiments revealed that the PhoBR regulon in Xoo comprised a wide
      range of genes. Nutrient transport and metabolism readjustments that resulted
      from PhoBR regulon activation may be responsible for growth attenuation. Our
      findings suggest that growth reduction regulated by PhoBR is a fitness cost of
      adaptation to phosphate starvation. PhoBR in Xoo is activated under phosphate
      limited conditions, which could exist in epiphytic and saprophytic surviving
      phases, and is strictly repressed within phosphate-rich host plants to minimize
      fitness costs.

PMID- 29575481
TI  - Counterion Specificity of Polyelectrolyte Brushes: Role of Specific Ion-Pairing
      Interactions.
AB  - We demonstrate here that the properties of poly (2-(methacryloyloxy) ethyl
      trimethylammonium chloride) brushes can be tuned by counterion species. When the
      brushes are exposed to external chloride (Cl- ) counterions, obvious dehydration
      and collapse are only observed at high salt concentrations. In the presence of
      very strongly chaotropic perchlorate (ClO4- ), the brushes strongly dehydrate and
      collapse at a very low salt concentration. For the strongly chaotropic
      thiocyanate ion (SCN- ), the changes in hydration and conformation of the brushes
      are similar to those observed for ClO4- but at a smaller extent at very low salt
      concentrations. With the addition of kosmotropic acetate (Ac- ), hydration of the
      brushes increases, accompanied by a swelling of the brushes in the low-salt
      concentration regime. In contrast, the brushes dehydrate and collapse with
      increasing concentration of Ac- in the high-salt-concentration regime. The
      counterion specificity of the brushes demonstrated here is determined by specific
      ion-pairing interactions through modulating the osmotic pressure within the
      brushes and the hydrophobicity of the ion pairs.

PMID- 29575483
TI  - Psychosis and sexual abuse: An interpretative phenomenological analysis.
AB  - OBJECTIVES: This study aimed to investigate the first-person perspective of
      psychosis sufferers who survived childhood sexual abuse. METHODS: Interpretative
      phenomenological analysis was employed to explore the experiences of 7 women with
      a history of sexual abuse and psychosis. RESULTS: Analysis generated six themes:
      (a) degradation of self, interlinking shame, guilt, and sometimes disgust; (b)
      body-self entrapment, experiencing bodily constraint and distortion; (c) a sense
      of being different to others, involving interpersonal problems; (d) unending
      struggle and depression, a pervasive sense of defeat; (e) psychotic condemnations
      and abuse, describing psychotic phenomena related to harm and sexual abuse; and
      (f) perception of links to the past, the links made from past abuse to current
      functioning. CONCLUSION: Participants suffered extreme psychological, physical,
      and interpersonal difficulties past and present. Psychotic experiences reported
      exhibited themes of condemnation by external entities and reflected the topic of
      sexual abuse. Participants did not generally link psychosis to their past abusive
      experiences.

PMID- 29575484
TI  - Shared decision-making in tinnitus care - An exploration of clinical encounters.
AB  - OBJECTIVES: This study examined clinical encounters between clinicians and
      patients to determine current practice for the diagnosis and treatment of
      tinnitus. The objective was to develop an understanding of the ideal clinical
      encounter that would facilitate genuine shared decision-making. DESIGN: Video
      ethnography was used to examine clinical encounters for the diagnosis and
      treatment of tinnitus. METHODS: Clinical encounters were video-recorded. Patients
      were interviewed individually following their clinic appointment. Data were
      analysed using constant comparison techniques from Grounded Theory. Initial
      inductive analyses were then considered against theoretical conceptualizations of
      the clinician-patient relationship and of the clinical encounter. RESULTS:
      Alignment between clinician and patient was found to be essential to a
      collaborative consultation and to shared decision-making. Clinician groups
      demonstrated variation in behaviour in the encounter; some asked closed questions
      and directed the majority of the consultation; others asked open questions and
      allowed patients to lead the consultation. CONCLUSIONS: A shift away from
      aetiology and physiological tests is needed so that tinnitus is managed as a
      persistent unexplained set of symptoms. This uncertainty is challenging for the
      medical professionals; lessons could be learned from the use of therapeutic
      skills. Further research is required to test techniques, such as the use of
      decision aids, to determine how we might create the ideal clinical encounter.
      Statement of contribution What is already known on this subject? Tinnitus is a
      condition in which sound is heard in the absence of an external source. Current
      approaches to managing tinnitus vary depending on clinical site (Hoare & Hall, ).
      In most instances, tinnitus does not have a straightforward medical cause.
      Tinnitus care is challenging to traditional biomedical encounters because the
      process of diagnosis may not lead to a defined treatment. Clinicians are required
      to consider not only what the tinnitus sounds like but more importantly, what it
      means for the affected individual. This requires a careful and skilled approach
      to eliciting a patient's current behaviour, coping, and preferences for both
      outcomes and treatment approaches. What does this study add? We provide the first
      in-depth description of decision-making in clinical services for tinnitus.
      Findings suggest a shift in focus is required to move away from the current
      prioritization of the biomedical treatment of tinnitus. There is variation to the
      extent different clinicians were able to deal with the uncertainty presented by
      the symptoms of tinnitus.

PMID- 29575485
TI  - Impact of a fatigue management in work programme on meeting work demands of
      individuals with rheumatic diseases: A pilot study.
AB  - INTRODUCTION: Work disability and job loss are serious consequences of rheumatic
      diseases (RDs), and fatigue is a symptom of RDs commonly reported to have an
      impact on work performance. A FAtigue ManagEment in Work (FAME-W) programme was
      developed to facilitate the self-management of fatigue in work. The present pilot
      study explored if FAME-W could facilitate individuals with RDs to manage fatigue
      in work and improve their ability to meet work demands. METHODS: Twenty-seven
      individuals with a variety of rheumatic diagnoses completed a 4-week, 2-h
      occupational therapy-led self-management programme. Each week focused on fatigue
      related topics, including fatigue and activity management, pain management and
      joint protection, mental well-being, effective communication with employers and
      work colleagues, and employment legislation. Individual workplace ergonomic
      assessments were also offered. Study measures (work function, fatigue, pain, mood
      and self-efficacy) were completed prior to starting FAME-W, immediately post
      intervention and 12 weeks post-intervention. RESULTS: Participants (56% male) had
      a mean age of 43 years. No significant improvements were observed immediately
      post-programme. However, at the 12-week follow-up, significant improvements were
      reported in meeting work demands (scheduling [p = 0.046], output [p = 0.002],
      physical [p = 0.003], mental [p = 0.016]), fatigue [p = 0.001], pain [p = 0.01],
      anxiety [p = 0.001], depression [p < 0.001], self-efficacy [p < 0.001] and
      Arthritis Impact Measurement Scales 2-Short Form (physical: p = 0.005; symptoms:
      p = 0.010; affect: p = 0.010; social: p = 0.001). CONCLUSIONS: Significant
      improvements were reported in participants' ability to meet various demands of
      their work 3 months post-FAME-W. These findings suggest that FAME-W has the
      potential to assist individuals with RDs to meet the demands of their work,
      although further research is required to test the effectiveness of this
      intervention.

PMID- 29575486
TI  - The Myosin5-mediated actomyosin motility system is required for Verticillium
      pathogenesis of cotton.
AB  - The vascular wilt fungus Verticillium dahliae is one of the most destructive
      pathogens of cotton (Gossypium hirsutum) and many other economically important
      dicot plants. Fungal pathogens require Myosin-mediated actomyosin motility system
      for colonization of their host plants; however, the mechanisms underlying this
      process have not been fully characterized for V. dahliae. Here, in a knock-out
      experiment, we characterized the role of VdMyo5, a member of the Myosin V family,
      before and during infection of cotton and Arabidopsis thaliana. The VdMyo5
      deletion mutant (DeltaVdmyo5) fungi showed obvious defects in the development of
      conidia and the polarized elongation of vegetative hyphae, but no inhibition of
      host root penetration. Overall, the DeltaVdmyo5 fungi exhibited dramatically
      reduced virulence in cotton and Arabidopsis, with almost no colonization in
      sections of host vascular tissue. We found labelled Myosin5-GFP to be
      specifically enriched at the hyphal tip, co-localized with FM4-64 labelled
      Spitzenkorper, which is the vesicle supply centre in filamentous fungi.
      Comparative secretome analysis revealed that proteins associated with cell wall
      modification and degradation of reactive oxygen species were significantly
      altered in mutant strains. Our results indicate that Myosin5 is required for
      vegetative growth and full virulence, possibly by regulating vesicle transport.
      The findings provide important insight into the cellular mechanisms of
      Verticillium pathogenesis.

PMID- 29575488
TI  - A randomized controlled clinical trial to assess crestal bone remodeling of four
      different implant designs.
AB  - BACKGROUND: It is claimed that bone remodeling is limited when the implant neck
      has microthreads and an internal abutment connection. However, comparative
      studies, excluding confounding factors, are scarce. AIM: This RCT aims to assess
      whether a coronal microthreaded design and an internal abutment connection
      affects crestal bone loss, up to one year of function. MATERIALS AND METHODS:
      Twenty-one maxillary edentulous patients were consecutively treated for a bar
      supported maxillary overdenture on four different implants with respectively:
      internal connection and microthreads on the implant neck (I MT); internal
      connection, no microthreads (I NMT), external connection, with microthreads (E
      MT), and external connection, without microthreads (E NMT). Other design
      features, s.a. width, surface topography, platform switch as well as surgical
      placement and prosthetic protocol were consistent. Implant survival and crestal
      bone loss in relation to the implant type were considered the main variables and
      a Friedman test for ordered alternatives was used to assess the difference in
      crestal bone loss between the different study implants. RESULTS: Twenty-one
      patients received 83 study implants. Three implants failed within three months
      and required replacement. The total survival rate was 96.39% after one year and
      based on 21 patients and 80 implants a mean crestal bone loss of 0.25 mm (SD:
      0.38; range: 0-1.48) was measured. After a follow-up of 3, 6, 12, and 21 months
      no statistically significant differences in crestal bone loss between the
      different study implants or the different time intervals could be identified.
      CONCLUSIONS: From this RCT, it is concluded that the implant-abutment connection
      and a microthreaded external thread configuration have limited influence on
      crestal bone remodeling. The latter can be considered a multifactorial process
      and is more dependent on other factors such as biologic considerations than on
      implant design.

PMID- 29575487
TI  - PDK1 governs thromboxane generation and thrombosis in platelets by regulating
      activation of Raf1 in the MAPK pathway.
AB  - : Essentials Phosphoinositide 3-kinase and MAPK pathways crosstalk via PDK1. PDK1
      is required for adenosine diphosphate-induced platelet activation and thromboxane
      generation. PDK1 regulates RAF proto-oncogene Ser/Thr kinase (Raf1) activation in
      the MAPK pathway. Genetic ablation of PDK1 protects against platelet-dependent
      thrombosis in vivo. SUMMARY: Background Platelets are dynamic effector cells with
      functions that span hemostatic, thrombotic and inflammatory continua.
      Phosphoinositide-dependent protein kinase 1 (PDK1) regulates protease-activated
      receptor 4-induced platelet activation and thrombus formation through glycogen
      synthase kinase3beta. However, whether PDK1 also signals through the ADP receptor
      and its functional importance in vivo remain unknown. Objective To establish the
      mechanism of PDK1 in ADP-induced platelet activation and thrombosis. Methods We
      assessed the role of PDK1 on 2MeSADP-induced platelet activation by measuring
      aggregation, thromboxane generation and phosphorylation events in the presence of
      BX-795, which inhibits PDK1, or by using platelet-specific PDK1 knockout mice and
      performing western blot analysis. PDK1 function in thrombus formation was
      assessed with an in vivo pulmonary embolism model. Results PDK1 inhibition with
      BX-795 reduced 2-methylthio-ADP (2MeSADP)-induced aggregation of human and murine
      platelets by abolishing thromboxane generation. Similar results were observed in
      pdk1-/- mice. PDK1 was also necessary for the phosphorylation of mitogen
      activated protein kinase kinase 1/2 (MEK1/2), extracellular signal-regulated
      kinase 1/2, and cytosolic phospholipase A2, indicating that PDK1 regulates an
      upstream kinase in the mitogen-activated protein kinase (MAPK) pathway. We next
      determined that this upstream kinase is Raf-1, a serine/threonine kinase that is
      necessary for the phosphorylation of MEK1/2, as pharmacological inhibition and
      genetic ablation of PDK1 were sufficient to prevent Raf1 phosphorylation.
      Furthermore, in vivo inhibition or genetic ablation of PDK1 protected mice from
      collagen/epinephrine-induced pulmonary embolism. Conclusion PDK1 governs
      thromboxane generation and thrombosis in platelets that are stimulated with
      2MeSADP by regulating activation of the MAPK pathway.

PMID- 29575489
TI  - Complex interactions between thalassemia defective alleles compromise screening
      and cause severe anemia in a Chinese family.

PMID- 29575490
TI  - Important patient and public (PPI) perspectives on addiction as a reason for
      performing euthanasia.

PMID- 29575492
TI  - Concerted Bimetallic Nanocluster Synthesis and Encapsulation via Induced Zeolite
      Framework Demetallation for Shape and Substrate Selective Heterogeneous
      Catalysis.
AB  - Bimetallic nanoparticle encapsulation in microporous zeolite crystals is a
      promising route for producing catalysts with unprecedented reaction
      selectivities. Herein, a novel synthetic approach was developed to produce PtZnx
      nanoclusters encapsulated inside zeolite micropores by introducing Pt2+ cations
      into a zincosilicate framework via ion exchange, and subsequent controlled
      demetallation and alloying with framework Zn. The resulting zeolites featured
      nanoclusters with sizes of approximately 1 nm, having an interatomic structure
      corresponding to a PtZnx alloy as confirmed by pair distribution function (PDF)
      analysis. These materials featured simultaneous shape and substrate specificity
      demonstrated by the selective production of p-chloroaniline from the competitive
      hydrogenation of p-chloronitrobenzene and 1,3-dimethyl-5-nitrobenzene.

PMID- 29575491
TI  - Optimization of reprogramming culture conditions for the generation of induced
      pluripotent stem cells from Col1a1 4F2A-Oct4-GFP mice with high efficiency.
AB  - A reprogrammable transgenic mouse strain, called Col1a1 4F2A-Oct4-GFP, was bred
      for the present study. Because the somatic cells of this mouse strain contain
      only two copies of each Yamanaka factor, these animals are inefficient at
      producing induced pluripotent stem cells (iPSCs; approx. 0.005%) under
      traditional culture conditions. With an optimized culture condition, the iPSC
      production rate of mouse embryonic fibroblasts (MEFs) of Col1a1 4F2A-Oct4-GFP
      mice (MEFCol1a14F2A-Oct4-GFP ) was increased to approximately 8%. Further,
      promotion of cell proliferation by serum supplementation did not enhance iPSC
      production. Inhibition of transforming growth factor beta (TGF-beta) in the serum
      by SB431542 neither affected the growth rate of MEFCol1a14F2A-Oct4-GFP nor
      promoted iPSC production. However, the use of the gamma-irradiated STO-NEO-LIF
      (gammaSNL) cells to serve as feeders for iPSC production resulted in a 5-fold
      higher rate of iPSC production than the use of gammaMEFICR feeders.
      Interestingly, the use of SB431542 with the gammaMEFICR -adopted system could
      eliminate this difference. RT-PCR-based comparative analysis further demonstrated
      that TGF-beta expression was 10-fold higher in gammaMEFICR than in gammaSNL
      cells. Consistent with previous reports, mesenchymal to epithelial transition was
      found to participate in the initial steps of reprogramming in the specific
      context of MEFCol1a14F2A-Oct4-GFP . Moreover, we found that the initial seeding
      density is one of the pivotal factors for determining a high efficiency of iPSC
      generation. The iPSCs efficiently generated from our MEFCol1a14F2A-Oct4-GFP
      resembled mouse embryonic stem cells (mESCs) in aspects of teratoma formation and
      germline transmission. Depending on the culture conditions, our Col1a1 4F2A-Oct4
      GFP mouse system can generate bona fide iPSCs with variable efficiencies, which
      can serve as a tool for interrogating the route taken by cells during somatic
      reprogramming.

PMID- 29575493
TI  - Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd2+
      Chemical Stimulus.
AB  - The on-column selective conversion of guanosine to thioguanosine (tG) yields
      modified oligomers that exhibit destabilisation over the fully complementary
      duplex. Restoration to a stabilised duplex is induced through thio-directed Cd2+
      coordination; a route for healing DNA damage. Short oligomers are G-specifically
      thiolated through a modified on-column protocol without the need for costly
      thioguanosine phosphoramidites. Addition of Cd2+ ions to a duplex containing a
      highly disrupted tG central mismatch sequence, 3'-A6 tG4 T6 -5', suggests a (tG)8
      Cd2 central coordination regime, resulting in increased base stacking and duplex
      stability. Equilibrium molecular dynamic calculations support the hypothesis of
      metal-induced healing of the thiolated duplex. The 2 nm displacement of the
      central tG mismatched region is dramatically reduced after the addition of a
      chemical stimuli, Cd2+ ions, returning to a minimized fluctuational state
      comparable to the unmodified fully complementary oligomer.

PMID- 29575494
TI  - Cortical depth profiles of luminance contrast responses in human V1 and V2 using
      7 T fMRI.
AB  - Neural activity in early visual cortex is modulated by luminance contrast.
      Cortical depth (i.e., laminar) contrast responses have been studied in monkey
      early visual cortex, but not in humans. In addition to the high spatial
      resolution needed and the ensuing low signal-to-noise ratio, laminar studies in
      humans using fMRI are hampered by the strong venous vascular weighting of the
      fMRI signal. In this study, we measured luminance contrast responses in human V1
      and V2 with high-resolution fMRI at 7 T. To account for the effect of
      intracortical ascending veins, we applied a novel spatial deconvolution model to
      the fMRI depth profiles. Before spatial deconvolution, the contrast response in
      V1 showed a slight local maximum at mid cortical depth, whereas V2 exhibited a
      monotonic signal increase toward the cortical surface. After applying the
      deconvolution, both V1 and V2 showed a pronounced local maximum at mid cortical
      depth, with an additional peak in deep grey matter, especially in V1. Moreover,
      we found a difference in contrast sensitivity between V1 and V2, but no evidence
      for variations in contrast sensitivity as a function of cortical depth. These
      findings are in agreement with results obtained in nonhuman primates, but further
      research will be needed to validate the spatial deconvolution approach.

PMID- 29575495
TI  - Wheat streak mosaic virus: a century old virus with rising importance worldwide.
AB  - Wheat streak mosaic virus (WSMV) causes wheat streak mosaic, a disease of cereals
      and grasses that threatens wheat production worldwide. It is a monopartite,
      positive-sense, single-stranded RNA virus and the type member of the genus
      Tritimovirus in the family Potyviridae. The only known vector is the wheat curl
      mite (WCM, Aceria tosichella), recently identified as a species complex of
      biotypes differing in virus transmission. Low rates of seed transmission have
      been reported. Infected plants are stunted and have a yellow mosaic of parallel
      discontinuous streaks on the leaves. In the autumn, WCMs move from WSMV-infected
      volunteer wheat and other grass hosts to newly emerged wheat and transmit the
      virus which survives the winter within the plant, and the mites survive as eggs,
      larvae, nymphs or adults in the crown and leaf sheaths. In the spring/summer, the
      mites move from the maturing wheat crop to volunteer wheat and other grass hosts
      and transmit WSMV, and onto newly emerged wheat in the fall to which they
      transmit the virus, completing the disease cycle. WSMV detection is by enzyme
      linked immunosorbent assay (ELISA), reverse transcription-polymerase chain
      reaction (RT-PCR) or quantitative RT-PCR (RT-qPCR). Three types of WSMV are
      recognized: A (Mexico), B (Europe, Russia, Asia) and D (USA, Argentina, Brazil,
      Australia, Turkey, Canada). Resistance genes Wsm1, Wsm2 and Wsm3 have been
      identified. The most effective, Wsm2, has been introduced into several wheat
      cultivars. Mitigation of losses caused by WSMV will require enhanced knowledge of
      the biology of WCM biotypes and WSMV, new or improved virus detection techniques,
      the development of resistance through traditional and molecular breeding, and the
      adaptation of cultural management tactics to account for climate change.

PMID- 29575496
TI  - Assessing canopy performance using carbonyl sulfide measurements.
AB  - Carbonyl sulfide (COS) is a tracer of ecosystem photosynthesis that can advance
      carbon cycle research from leaf to global scales; however, a range of newly
      reported caveats related to sink/source strength of various ecosystem components
      hinder its application. Using comprehensive eddy-covariance and chamber
      measurements, we systematically measure ecosystem contributions from leaf, stem,
      soil, and litter and were able to close the ecosystem COS budget. The relative
      contributions of nonphotosynthetic components to the overall canopy-scale flux
      are relatively small (~4% during peak activity season) and can be independently
      estimated based on their responses to temperature and humidity. Converting COS to
      photosynthetic CO2 fluxes based on the leaf relative uptake of COS/CO2 , faces
      challenges due to observed daily and seasonal changes. Yet, this ratio converges
      around a constant value (~1.6), and the variations, dominated by light intensity,
      were found unimportant on a flux-weighted daily time-scale, indicating a mean
      ratio of daytime gross-to-net primary productivity of ~2 in our ecosystem. The
      seasonal changes in the leaf relative uptake ratio may indicate a reduction in
      mesophyll conductance in winter, and COS-derived canopy conductance permitted
      canopy temperature estimate consistent with radiative skin temperature. These
      results support the feasibility of using COS as a powerful and much-needed means
      of assessing ecosystem function and its response to change.

PMID- 29575498
TI  - Binding sites for pentatricopeptide repeat proteins differentially activate
      chloroplast transgenes.

PMID- 29575497
TI  - Utility of Doppler sonography for renal artery stenosis screening in obese
      children with hypertension.
AB  - Pediatric hypertension guidelines recommend Doppler renal ultrasonography as a
      screening study for the evaluation of possible renal artery stenosis (RAS) in
      normal-weight children >= 8 years of age who are suspected of having RAS and who
      will cooperate with the procedure. Obese children are excluded because of
      technical and vascular concerns. There are no data on RI in obese children. This
      is a retrospective review of children aged 1.5-18 who received Doppler imaging
      studies over a 10-year period. A total of 174 patients were studied. There was no
      significant difference between the RI values based on BMI. Of the 174 individuals
      in the study 22 obtained follow-up CT/MRA after abnormal Doppler ultrasounds. On
      advanced imaging 3 were confirmed to have RAS. Obesity does not seem to influence
      RI.RI alone should not be used as a screening tool for RAS. An approach toward
      diagnosis is suggested based on BMI, renin levels, and ultrasound.

PMID- 29575499
TI  - Keeping secrets: Leslie E. Keeley, the gold cure and the 19th-century
      neuroscience of addiction.
AB  - BACKGROUND AND AIMS: Dr Leslie E. Keeley was perhaps the world's most famous
      addiction cure doctor at the turn of the 20th century, but mainstream medicine
      dismissed him as a quack because he dispensed a secret cure. This paper aims to
      describe Keeley's now largely forgotten story and to draw attention to the role
      of contextual issues in the acceptance or rejection of any theory of addiction,
      particularly the neuroscientific theories of the early 21st century. METHODS:
      This study is a qualitative assessment and contextualization of historical
      documents. Its main sources are archival and are, for the most part, unknown to
      historians. The paper also offers intellectual and historical context that is
      drawn from leading historical and sociological analyses. RESULTS: Keeley's
      addiction cure was dismissed as quackery because it failed to meet the changing
      standards of late 19th-century professional medicine. This begs us to consider
      contextual issues in any assertion of the viability of addiction therapeutics, in
      the present as well the past. CONCLUSIONS: Keeley's near erasure from the
      historical record was a consequence of a broader, late 19th-century medical power
      struggle that took precedence over the testimony of tens of thousands of
      satisfied patients who claimed that Keeley's cure worked. Context matters in the
      assessment of the viability of theories of addiction from the past, but also from
      the present. Historians and social scientists are well placed to make those
      assessments.

PMID- 29575500
TI  - Future warming and acidification result in multiple ecological impacts to a
      temperate coralline alga.
AB  - Coralline algae are a crucial component of reef systems, stabilising reef
      substrate, providing habitat and contributing to accretion. Coralline algae and
      their surface microbial biofilms are also important as settlement cues for marine
      invertebrates, yet few studies address the impact of future environmental
      conditions on interactions between coralline algae, reef microbes and settlement
      by larvae of marine invertebrates. We exposed the temperate coralline algal
      species Amphiroa gracilis to warming and/or acidification scenarios for 21 days.
      Algae became bleached but photosystem II function was not measurably impacted.
      Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and
      the structure of the prokaryotic community associated with A. gracilis was
      altered. Coralline algae in ambient conditions were dominated by
      Alphaproteobacteria from the Rhodobacteraceae including Loktonella; those under
      warming were dominated by Bacteroidetes and Verrucomicrobia; acidification
      resulted in less Loktonella and more Planctomycetes and a combination of warming
      and acidification caused increases in Bacteroidetes, Verrucomicrobia and the
      Alphaproteobacteria family Hyphomonadaceae. These experiments indicate that
      predicted future environmental change may reduce the ability of some temperate
      reef coralline algae and associated reef microbes to facilitate settlement of
      invertebrate larvae as well as having a direct impact to algae via bleaching.

PMID- 29575501
TI  - Liquid chromatography/isotope ratio mass spectrometry analysis of halogenated
      benzoates for characterization of the underlying degradation reaction in Thauera
      chlorobenzoica CB-1T.
AB  - RATIONALE: Halogenated benzoic acids occur in the environment due to their
      widespread agricultural and pharmaceutical use. Compound-specific stable isotope
      analysis (CSIA) has developed over the last decades for investigation of in situ
      transformation and reaction mechanisms of environmental pollutants amenable by
      gas chromatography (GC). As polar compounds are unsuitable for GC analysis we
      developed a method to perform liquid chromatography (LC)/CSIA for halogenated
      benzoates. METHODS: LC/isotope ratio mass spectrometry (IRMS) utilizing a LC
      Surveyor pump coupled to a MAT 253 isotope ratio mass spectrometer via a LC
      Isolink interface was applied. For chromatographic separation a YMC-Triart C18
      column and a potassium hydrogen phosphate buffer (150 mM, pH 7.0, 40 degrees C,
      200 MUL mL-1 ) were used, followed by wet oxidation deploying 1.5 mol L-1 ortho
      phosphoric acid and 200 g L-1 sodium peroxodisulfate at 75 MUL mL-1 . RESULTS:
      Separation of benzoate and halogenated benzoates could be achieved in less than
      40 min over a concentration range of 2 orders of magnitude. Under these
      conditions the dehalogenation reaction of Thauera chlorobenzoica 3CB-1T using 3
      chloro-, 3-bromo- and 4-chlorobenzoic acid was investigated resulting in inverse
      carbon isotope fractionation for meta-substituted benzoic acids and minor normal
      fractionation for para-substituted benzoic acids. Together with the respective
      growth rates this led to the assumption that dehalogenation of para-halobenzoic
      acids follows a different mechanism from that of meta-halobenzoic acids.
      CONCLUSIONS: A new LC/IRMS method for the quantitative determination of
      halogenated benzoates was developed and used to investigate the in vivo
      transformation pathways of these compounds, providing some insights into
      degradation and removal of these widespread compounds by T. chlorobenzoica 3CB-1T
      .

PMID- 29575502
TI  - Potential global distribution of Diabrotica species and the risks for
      agricultural production.
AB  - BACKGROUND: Despite efforts in the last few decades to prevent biological
      invasions, agricultural pests continue to spread as a result of globalization and
      international trade. This study was conducted to identify suitable areas for the
      occurrence of four Diabrotica species and to assess the potential impact of these
      species in a scenario of invasion followed by spread throughout the estimated
      suitable regions. RESULTS: Our findings reveal that a large proportion of the
      suitable areas for Diabrotica species overlap with cultivated areas. Niche
      analyses also demonstrated that these species occupy a small proportion of the
      suitable habitats available to them, indicating that, if new areas are invaded,
      there is a risk of spread throughout adjacent regions. CONCLUSION: Most of the
      suitable areas for Diabrotica species overlap with highly productive agricultural
      areas, suggesting that a potential spread of these species may cause economic
      loss. Our study provides a valuable contribution to the development of tools
      aiming to predict the potential spread of these species throughout the world. (c)
      2018 Society of Chemical Industry.

PMID- 29575503
TI  - Kidney transplant outcomes: Does position on the match-run matter?

PMID- 29575504
TI  - A Building Brick Principle to Create Transparent Composite Films with Multicolor
      Emission and Self-Healing Function.
AB  - A cellulose paper is used impregnated with light-emitting CdTe nanocrystals and
      carbon dots, and filled with a polyurethane to fabricate uniform transparent
      composite films with bright photoluminescence of red (R), green (G), and blue (B)
      (RGB) colors. A building brick-like assembly method is introduced to realize RGB
      multicolor emission patterns from this composite material. By sectioning out
      individual pixels from monochrome-emissive composite sheets, the advantage of the
      self-healing properties of polyurethane is taken to arrange and weld them into a
      RGB patterned fabric by brief exposure to ethanol. This provides an approach to
      form single layer RGB light-emitting pixels, such as potentially required in the
      display applications, without the use of any lithographic or etching processing.
      The method can utilize a wide range of different solution-based kinds of light
      emitting materials.

PMID- 29575505
TI  - The psychosocial impact of 22q11 deletion syndrome on patients and families: A
      systematic review.
AB  - The 22q11 deletion syndrome (22q11DS) is one of the most common genomic disorders
      in humans, affecting around 1:2,000 to 1: 4,000 people. 22q11DS affects multiple
      body systems and is associated with multiple physical problems. Given the high
      rate of physical morbidity associated with the 22q11DS, it was hypothesized that
      it would exert a high psychosocial impact on patients and their relatives. To
      investigate this, a systematic review of the literature and narrative synthesis
      was performed. Three major themes emerged. First, the complex and conflicting
      emotions experienced by family members resulting from the diagnosis. Second, the
      pervasive educational and health-care challenges associated with the diagnosis
      and third that people affect by 22q11DS strived for individualism. The results of
      this review help to inform clinical management of families with 22q11DS.

PMID- 29575506
TI  - Hydrido Complexes of Calcium: A New Family of Molecular Alkaline-Earth-Metal
      Compounds.
AB  - The application of solid calcium hydride CaH2 has been mostly confined to its use
      as a desiccant, although its catalytic activity has long been known. Since the
      first isolation of a well-defined molecular calcium hydride in 2006, the past
      decade has witnessed a gradual emergence of this new family of compounds.
      Although the detrimental Schlenk equilibrium has kept the number of examples low,
      the novelty of their reactivity, especially in small-molecule activation, holds
      great promise. This Minireview gives an overview of the molecular calcium
      hydrides reported to date, highlighting their synthesis, structure, and
      reactivity.

PMID- 29575507
TI  - Effects of clinical parameters on patient-reported outcome in cataract patients:
      a multicentre study.
AB  - PURPOSE: Ophthalmologists tend to evaluate the results of cataract surgery by
      focusing on the clinical visual and refractive outcomes and the incidence of
      complications, where patients' main interest might be their ability to perform
      daily activities. Therefore, there appears to be a need for optimizing effective
      communication between patients and ophthalmologist about the outcome of cataract
      surgery. The aim of this multicentre study was to determine the effects of
      whether the surgery was performed in one or two eyes, ocular comorbidity and per-
      and postoperative complications on visual function experienced by patients
      measured with the Catquest-9SF. METHODS: To measure patient-reported outcomes,
      Catquest-9SF data were collected between 2014 and 2015 in five Dutch hospitals.
      Data from 870 pairs of questionnaires - completed before and after cataract
      surgery - were compared with clinical data. Clinical data, retrieved from
      patients' medical files, consisted of one or two eye surgery, ocular comorbidity
      and per- and postoperative complications. RESULTS: Quality of vision improved
      more in patients who had surgery in both eyes and had fewer postoperative
      complications (both p < 0.001). We found a nonsignificant trend that quality of
      vision was worse when ocular comorbidity was present. No significant effect of
      peroperative complications was observed. CONCLUSION: Our results emphasize the
      added value of the Catquest-9SF as a tool for visual function experienced by
      patients; the additional information can complement clinical parameters to
      improve patient-centred approaches in clinical practice.

PMID- 29575508
TI  - Roles of pH in control of cell proliferation.
AB  - Precise spatiotemporal regulation of intracellular pH (pHi ) is a prerequisite
      for normal cell function, and changes in pHi or pericellular pH (pHe ) exert
      important signalling functions. It is well established that proliferation of
      mammalian cells is dependent on a permissive pHi in the slightly alkaline range
      (7.0-7.2). It is also clear that mitogen signalling in nominal absence of HCO3-
      is associated with an intracellular alkalinization (~0.3 pH unit above steady
      state pHi ), which is secondary to activation of Na+ /H+ exchange. However, it
      remains controversial whether this increase in pHi is part of the mitogenic
      signal cascade leading to cell cycle entry and progression, and whether it is
      relevant under physiological conditions. Furthermore, essentially all studies of
      pHi in mammalian cell proliferation have focused on the mitogen-induced G0-G1
      transition, and the regulation and roles of pHi during the cell cycle remain
      poorly understood. The aim of this review is to summarize and critically discuss
      the possible roles of pHi and pHe in cell cycle progression. While the focus is
      on the mammalian cell cycle, important insights from studies in lower eukaryotes
      are also discussed. We summarize current evidence of links between cell cycle
      progression and pHi and discuss possible pHi - and pHe sensors and signalling
      pathways relevant to mammalian proliferation control. The possibility that
      changes in pHi during cell cycle progression may be an integral part of the
      checkpoint control machinery is explored. Finally, we discuss the relevance of
      links between pH and proliferation in the context of the perturbed pH
      homoeostasis and acidic microenvironment of solid tumours.

PMID- 29575509
TI  - Patient Selection by Tumor Markers in Liver Transplantation for Advanced
      Hepatocellular Carcinoma.
AB  - Although far advanced hepatocellular carcinoma (HCC) is generally considered a
      contraindication for liver transplantation (LT), biologically favorable tumors
      among them could show acceptable results. However, it is still unclear which
      tumors can be treated with LT. Data were collected on adult patients who
      underwent LT for HCC beyond the Milan criteria in 8 Korean LT centers between
      January 2000 and June 2013. Far advanced HCC was defined as HCC with the largest
      tumor >= 10 cm, 10 or more tumor nodules, or accompanying macrovascular invasion.
      A total of 688 patients, including 169 with far advanced HCC, were enrolled in
      this study. The 5-year overall and recurrence-free survival rates were 60.4% and
      55.1%, respectively, for all patients but only 28.7% and 24.8%, respectively, for
      patients with far advanced HCC (P < 0.001). Both preoperative alpha-fetoprotein
      (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) were
      significant risk factors for HCC recurrence after LT. In particular, AFP + PIVKA
      II combined was a better predictor than either marker alone. Of all far advanced
      HCC patients with available AFP and PIVKA-II levels, 45 (30.8%) had low AFP +
      PIVKA-II (<=300) and their 5-year overall and recurrence-free survival rate were
      47.8% and 53.4%, respectively, which were acceptable and significantly superior
      to those of patients with AFP (ng/mL) + PIVKA-II (nAU/mL) > 300 (21.0% and 10.8%,
      respectively; P < 0.001). In conclusion, patients with favorable HCC had
      acceptable outcomes after LT even when their tumors were extremely advanced. AFP
      + PIVKA-II gave reliable information about the tumor biology of far advanced HCC.
      Liver Transplantation 00 000-000 2018 AASLD.

PMID- 29575510
TI  - Pathological features of intestinal T-cell lymphoma in Shiba dogs in Japan.
AB  - Intestinal T-cell lymphoma is being more frequently diagnosed in dogs owing to
      the wide availability of endoscopy and clonality analysis in veterinary medicine.
      However, no epidemiological study on intestinal T-cell lymphoma has been
      previously performed, and hence, information about dog breed, age and sex
      distributions of intestinal T-cell lymphoma has largely remained unclear. In this
      study, breed predisposition to canine intestinal T-cell lymphoma was determined
      by calculating odds ratios and 95% confidential intervals. Of the 43 breeds
      identified, 7 appeared to have an increased risk of developing intestinal T-cell
      lymphoma, including Shiba dogs, German shepherds, Cairn terriers, Boston
      terriers, Papillons, Pugs and Maltese. Immunohistochemistry of representative
      Shiba cases revealed ubiquitous cytotoxic immunophenotype in both large and small
      cell lymphomas. Interestingly, CD20 co-expression was observed in 11% of cases.
      It could potentially be aberrant expression of CD20 or neoplastic transformation
      of a normal subset of CD20-positive T-cells. A comparison of mean age between
      representative breeds revealed that Shiba dogs were slightly younger than
      Miniature Dachshunds (P < .05). However, there was no difference in survival
      between the 2 breeds. As Shiba dogs are predisposed to chronic enteropathy, there
      may be underlying inflammatory process contributing to lymphomagenesis of
      intestinal T-cell lymphoma in this breed. Our findings provide insights into the
      underlying pathogenesis of breed-specific canine intestinal T-cell lymphoma.

PMID- 29575511
TI  - Triplex Formation by Oligonucleotides Containing Organomercurated Base Moieties.
AB  - Homothymine oligonucleotides with a single 5-mercuricytosine or 5-mercuriuracil
      residue at their termini have been synthesized and their capacity to form
      triplexes has been examined with an extensive array of double-helical targets. UV
      and circular dichroism (CD) melting experiments revealed the formation and
      thermal denaturation of pyrimidine?purine*pyrimidine-type triple helices with all
      oligonucleotide combinations studied. Nearly all triplexes were destabilized upon
      mercuration of the 3'-terminal residue of the triplex-forming oligonucleotide, in
      all likelihood due to competing intramolecular HgII -mediated base pairing. Two
      exceptions from this general pattern were, however, observed: 5-mercuricytosine
      was stabilizing when placed opposite to a T?A or A?T base pair. The stabilization
      was further amplified in the presence of 2-mercaptoethanol (but not hexanethiol,
      thiophenol or cysteine), suggesting a stabilizing interaction other than HgII 
      mediated base pairing.

PMID- 29575512
TI  - The role of unregulated care providers in Canada-A scoping review.
AB  - AIMS AND OBJECTIVES: This scoping review explored: (i) the role of unregulated
      care providers in the healthcare system; (ii) their potential role on
      interprofessional teams; (iii) the impact of unregulated care provider's role on
      quality of care and patient safety; and (iv) education and employment standards.
      BACKGROUND: Unregulated care providers in Canada assist older adults with
      personal support and activities of daily living in a variety of care settings. As
      the care needs of an aging population become increasingly complex, the role of
      unregulated care providers in healthcare delivery has also evolved. Currently,
      many unregulated care providers are performing tasks previously performed by
      regulated health professionals, with potential implications for quality of care
      and patient safety. Information is fragmented on the role, education and
      employment standards of unregulated care providers. METHODS: A scoping review was
      conducted following the methods outlined by Arksey and O'Malley (International
      Journal of Social Research Methodology, 8, 2005, 19) and Levac, Colquhoun, and
      O'Brien (Implementation Science, 5, 2010, 69). An iterative search of published
      and grey literature was conducted from January 2000 to September 2016 using
      Medline, CINAHL, SCOPUS and Google. Inclusion and exclusion criteria were applied
      to identify relevant studies published in English. RESULTS: The search yielded 63
      papers for review. Results highlight the evolving role of unregulated care
      providers, a lack of recognition and a lack of authority for unregulated care
      provider decision-making in patient care. Unregulated care providers do not have
      a defined scope of practice. However, their role has evolved to include
      activities previously performed by regulated professionals. Variations in
      education and employment standards have implications for quality of care and
      patient safety. CONCLUSIONS: Unregulated care providers are part of an important
      workforce in the long-term care and community sectors in Canada. Their evolving
      role should be recognised and efforts made to leverage their experience on
      interprofessional teams and reduce variations in education and employment
      standards. IMPLICATIONS FOR PRACTICE: This study highlights the evolving role of
      unregulated care providers in Canada and presents a set of recommendations for
      implementation at micro, meso, and macro policy levels.

PMID- 29575513
TI  - Nosema ceranae in Apis mellifera: a 12 years postdetection perspective.
AB  - Nosema ceranae is a hot topic in honey bee health as reflected by numerous papers
      published every year. This review presents an update of the knowledge generated
      in the last 12 years in the field of N. ceranae research, addressing the routes
      of transmission, population structure and genetic diversity. This includes
      description of how the infection modifies the honey bee's metabolism, the immune
      response and other vital functions. The effects on individual honey bees will
      have a direct impact on the colony by leading to losses in the adult's
      population. The absence of clear clinical signs could keep the infection
      unnoticed by the beekeeper for long periods. The influence of the environmental
      conditions, beekeeping practices, bee genetics and the interaction with
      pesticides and other pathogens will have a direct influence on the prognosis of
      the disease. This review is approached from the point of view of the
      Mediterranean countries where the professional beekeeping has a high
      representation and where this pathogen is reported as an important threat.

PMID- 29575514
TI  - A 20-year trends in renal disease mortality in Ghana: A review of autopsies.
AB  - AIM: Data on the changing levels in renal morbidity and mortality are scant
      globally. We sought to assess trends in renal disease mortality and attributable
      causes over a twenty-year period in Ghana. METHODS: A retrospective analysis of
      20-year autopsy records of the Pathology Departments of leading teaching
      hospitals in Ghana, (Korle-Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye
      Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data
      comprising of autopsies from in-patients, community cases and coroners' cases
      were used. We defined primary cause of death as death directly due to renal
      disease and secondary cause of death as death in which renal disease was a
      comorbid or contributing factor. RESULTS: Over the period, there were a total of
      94,309 deaths of which 5608 were attributed to renal disease (5.9/100). Mortality
      rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to
      2013 (10.8%). Similar trends were observed among males and females during the
      same period. However, males had slightly higher mortality rates (6.6%; 95% C.I.
      46.1%-6.8%) compared to females (5.6%; 95% C.I. 5.4%-5.8%; p=0.271). The major
      leading attributable causes of renal disease death include end stage renal
      disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases.
      Hypertensive heart disease accounted for 30.0% of all secondary cause of death
      while congestive heart disease and septicaemia accounted for 13.0% and 12.0%
      respectively. CONCLUSIONS: We observed marked increase in renal disease mortality
      rate during the last few years predominantly driven by chronic and infectious
      related renal diseases as main cause, and hypertensive heart disease and
      congestive heart failure as main secondary causes. Measures geared towards
      prevention, treatment and managing such conditions may impact on the reduction of
      renal disease mortality rate among Ghanaian populations.

PMID- 29575515
TI  - Conserved structural features anchor biofilm-associated RTX-adhesins to the outer
      membrane of bacteria.
AB  - Repeats-in-toxin (RTX) adhesins are present in many Gram-negative bacteria to
      facilitate biofilm formation. Previously, we reported that the 1.5-MDa RTX
      adhesin (MpIBP) from the Antarctic bacterium, Marinomonas primoryensis, is
      tethered to the bacterial cell surface via its N-terminal Region I (RI). Here, we
      show the detailed structural features of RI. It has an N-terminal periplasmic
      retention domain (RIN), a central domain (RIM) that can insert into the beta
      barrel of an outer-membrane pore protein during MpIBP secretion, and three
      extracellular domains at its C terminus (RIC) that transition the protein into
      the extender region (RII). RIN has a novel beta-sandwich fold with a similar
      shape to betagamma-crystallins and tryptophan RNA attenuation proteins. Because
      RIM undergoes fast and extensive degradation in vitro, its narrow cylindrical
      shape was rapidly measured by small-angle X-ray scattering before proteolysis
      could occur. The crystal structure of RIC comprises three tandem beta-sandwich
      domains similar to those in RII, but increasing in their hydrophobicity with
      proximity to the outer membrane. In addition, the key Ca2+ ion that rigidifies
      the linkers between RII domains is not present between the first two of these RIC
      domains. This more flexible RI linker near the cell surface can act as a 'pivot'
      to help the 0.6-MUm-long MpIBP sweep over larger volumes to find its binding
      partners. Since the physical features of RI are well conserved in the RTX
      adhesins of many Gram-negative bacteria, our detailed structural and
      bioinformatic analyses serve as a model for investigating the surface retention
      of biofilm-forming bacteria, including human pathogens.

PMID- 29575516
TI  - Diabetes impacts prediction of cirrhosis and prognosis by non-invasive fibrosis
      models in non-alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) patients with
      diabetes are at increased risk of cirrhosis and liver-related death, and thus
      accurate fibrosis assessment in these patients is important. We examined the
      ability of non-invasive fibrosis models to determine cirrhosis and outcomes in
      NAFLD patients with and without diabetes. METHODS: Non-alcoholic fatty liver
      disease patients diagnosed between 2006 and 2015 had Hepascore, NAFLD fibrosis
      score (NFS), APRI and FIB-4 scores calculated at baseline and were followed up
      for outcomes of overall and liver-related mortality/liver transplantation,
      hepatic decompensation and hepatocellular carcinoma (HCC). Model accuracy was
      determined by Harrell's C-index and by Kaplan-Meier analysis. RESULTS: A total of
      284 patients (53% diabetic, 15% cirrhotic) were followed up for a median of 51.4
      months, (range 6.1-146). During follow-up, diabetic patients had a greater risk
      of liver-related death/transplantation, HR 3.4 (95% CI 1.2-9.1) decompensation,
      HR 4.7 (95% CI 2.0-11.3) and HCC, HR 2.9 (95% CI 1.2-7.3). Among 241 subjects
      with a baseline liver biopsy, the accuracy of Hepascore, APRI and FIB-4 for
      predicting cirrhosis was lower amongst diabetics compared to non-diabetics (P <
      .005 for all). Model accuracy apart from Hepascore, was also significantly lower
      for predicting liver death/transplantation in patients with diabetes. No patient
      with a low fibrosis score and without diabetes developed liver decompensation or
      HCC, whereas up to 21% of diabetic patients with a low fibrosis score developed
      liver decompensation and up to 27% developed HCC at 5 years. CONCLUSIONS: Non
      invasive scoring systems are less accurate at predicting cirrhosis and liver
      related outcomes in patients with NAFLD and diabetes.

PMID- 29575517
TI  - Genetic counseling among minority populations in the era of precision medicine.
AB  - Precision medicine includes the use of genetic variation to determine the
      prevention, pathology, management, and treatment of disease, which has the
      potential to significantly change the practice of healthcare. As such, its
      success depends on (a) having reliable information about the effects of genetic
      variation on disease processes; and (b) the patient's understanding of their own
      genetic makeup such that they can use that information to affect their lifestyle
      and diet. Given the history of low engagement of under-represented minority
      populations in both clinical genetic services and genetic research, both of these
      aspects will be challenged and must be addressed before the benefits of precision
      medicine will be fully realized. Reflecting on lessons learned in the field of
      cancer genetic counseling, we present key issues to consider as we look forward
      to providing genetic counseling to minority communities in the context of
      precision medicine.

PMID- 29575518
TI  - Narrative insight in psychosis: The relationship with spiritual and religious
      explanatory frameworks.
AB  - OBJECTIVE: When considering psychosis, the concept of narrative insight has been
      offered as an alternative to clinical insight in determining individuals'
      responses to their difficulties, as it allows for a more holistic and person
      centred framework to be embraced within professional practice. This study aims to
      explore the validity of the narrative insight construct within a group of people
      who have experienced psychosis. DESIGN: Inductive qualitative methods were used
      to explore how eight participants utilized spiritual or religious explanatory
      frameworks for their experiences of psychosis and to consider these in relation
      to the construct of narrative insight. METHODS: Semi-structured interviews were
      undertaken with individuals who identified themselves as interested in spiritual
      or religious ideas and whose self-reported experiences which were identified as
      akin to psychosis by experienced academic clinicians. Transcriptions from these
      interviews were subject to interpretative phenomenological analysis within a
      broader research question; a selection of themes and data from the resultant
      phenomenological structure are explored here for their relevance to narrative
      insight. RESULTS: Participants discussed spiritual and biological explanations
      for their experiences and were able to hold alternative potential explanations
      alongside each other. They were reflective regarding the origins of their
      explanations and would describe a process of testing and proof in relation to
      them. CONCLUSIONS: These findings suggest that the narrative insight construct
      has the potential to be a valid approach to understanding experiences of
      psychosis, and challenge the dominance of the clinical insight construct within
      clinical practice. PRACTITIONER POINTS: Clinicians should value the explanatory
      framework for experiences which are provided by individuals experiencing
      psychosis, and encourage them to develop a framework which is coherent to their
      own world view rather than predominantly pursuing a biomedical explanation.
      Assessments of psychosis should be adapted to include an understanding of the
      cohesiveness of the individual's explanatory framework and personal value to
      them, with a reduced focus on their acceptance of biomedical models of 'illness'.
      Care and care research for individuals experiencing psychosis should consider the
      value of narrative insight within future developments.

PMID- 29575519
TI  - Presence of koilocytosis in low-grade smears of high-risk HPV-positive women is a
      negative predictor for cervical intraepithelial neoplasia grade 3 or more.
AB  - OBJECTIVE: The Netherlands converted to high-risk (hr)HPV-based screening in
      2017. An increase in referral of hrHPV-positive women with low risk for cervical
      intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of
      unjustified referrals will have priority. The relevance of koilocytosis in
      relation to the underlying risk of high-grade CIN in a primary HPV screening
      setting is unclear. The aim was to investigate whether the risk for CIN3+ differs
      between hrHPV-positive atypical squamous cells of undetermined significance (ASC
      US)/low-grade squamous intraepithelial lesion (LSIL) with or without
      koilocytosis. METHODS: Retrospective cohort study, using data from the Dutch
      national pathology database (PALGA). The population was 1201 hrHPV-positive women
      with cytological diagnosis of ASC-US/LSIL. Reporting of koilocytosis was assessed
      as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC-US/LSIL
      cytology stratified by presence or absence of koilocytosis. Crude and adjusted
      odds ratios were determined. RESULTS: Koilocytosis was present in 40.1% of ASC-US
      and 45.9% of LSIL cases. CIN3+ is significantly less often found when
      koilocytosis is present (7.8% for hrHPV-positive ASC-US with- vs 15.8% without
      koilocytosis). For hrHPV-positive LSIL this was 11.7% vs 20.2%. The crude and
      adjusted odds ratios for CIN3+ was 0.45 for hrHPV-positive ASC-US and 0.52 for
      hrHPV-positive LSIL. CONCLUSIONS: The presence of koilocytosis is a negative
      predictor of CIN3+. The risk of hrHPV-positive ASC-US with koilocytosis is in the
      same range as hrHPV-positive/cytology negative cases and in a setting of primary
      hrHPV screening these cases could be followed conservatively by repeat cytology.
      The results should be confirmed by the first data from the Dutch HPV-based
      screening programme.

PMID- 29575520
TI  - Sulfoximidations of Benzylic C-H bonds by Photocatalysis.
AB  - An efficient photocatalytic functionalization of compounds with benzylic C-H
      bonds by sulfoximidation in visible light is described. The mild reaction
      conditions allow the use of a broad array of substrates, including diarylmethane,
      alkyl arenes, arylacetonitrile, 2-arylacetate, and alkynyl aryl methanes. The
      sulfoximidation process is highly chemoselective and leads to the corresponding
      sulfoximines in generally good yields. Mechanistic investigations suggested the
      intermediacy of sulfoximidoyl radicals.

PMID- 29575521
TI  - Nickel Fluorocarbene Metathesis with Fluoroalkenes.
AB  - Alkene metathesis with directly fluorinated alkenes is challenging, limiting its
      application in the burgeoning field of fluoro-organic chemistry. A new nickel
      tris(phosphite) fluoro(trifluoromethyl)carbene complex ([P3 Ni]=CFCF3 ) reacts
      with CF2 =CF2 (TFE) or CF2 =CH2 (VDF) to yield both metallacyclobutane and
      perfluorocarbene metathesis products, [P3 Ni]=CF2 and CR2 =CFCF3 (R=F, H). The
      reaction of [P3 Ni]=CFCF3 with trifluoroethylene also yields metathesis products,
      [P3 Ni]=CF2 and cis/trans-CFCF3 =CFH. However, unlike reactions with TFE and VDF,
      this reaction forms metallacyclopropanes and fluoronickel alkenyl species,
      resulting presumably from instability of the expected metallacyclobutanes. DFT
      calculations and experimental evidence established that the observed
      metallacyclobutanes are not intermediates in the formation of the observed
      metathesis products, thus highlighting a novel variant of the Chauvin mechanism
      enabled by the disparate four-coordinate transition states.

PMID- 29575522
TI  - Phosphate starvation response controls genes required to synthesize the phosphate
      analog arsenate.
AB  - Environmental arsenic poisoning affects roughly 200 million people worldwide. The
      toxicity and mobility of arsenic in the environment is significantly influenced
      by microbial redox reactions, with arsenite (AsIII ) being more toxic than
      arsenate (AsV ). Microbial oxidation of AsIII to AsV is known to be regulated by
      the AioXSR signal transduction system and viewed to function for detoxification
      or energy generation. Here, we show that AsIII oxidation is ultimately regulated
      by the phosphate starvation response (PSR), requiring the sensor kinase PhoR for
      expression of the AsIII oxidase structural genes aioBA. The PhoRB and AioSR
      signal transduction systems are capable of transphosphorylation cross-talk,
      closely integrating AsIII oxidation with the PSR. Further, under PSR conditions,
      AsV significantly extends bacterial growth and accumulates in the lipid fraction
      to the apparent exclusion of phosphorus. This could spare phosphorus for nucleic
      acid synthesis or triphosphate metabolism wherein unstable arsenic esters are not
      tolerated, thereby enhancing cell survival potential. We conclude that AsIII
      oxidation is logically part of the bacterial PSR, enabling the synthesis of the
      phosphate analog AsV to replace phosphorus in specific biomolecules or to
      synthesize other molecules capable of a similar function, although not for total
      replacement of cellular phosphate.

PMID- 29575523
TI  - Counterpoint: Provider moral distress in end-of-life oncology care is a moral
      crutch.

PMID- 29575524
TI  - Distribution of IFITM3 polymorphism (dbSNP: rs12252) in mestizo populations in
      four states of Mexico.
AB  - Interferon-inducible transmembrane protein 3 (IFITM3) participates in the defense
      against viral infections. This study identified and compared the frequency of the
      IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western
      Mexican allelic frequencies (frequency of the "C" allele = 0.18) differ from some
      American, East Asian and European populations.

PMID- 29575525
TI  - Mesoporous Hollow Sb/ZnS@C Core-Shell Heterostructures as Anodes for High
      Performance Sodium-Ion Batteries.
AB  - Combining the advantage of metal, metal sulfide, and carbon, mesoporous hollow
      core-shell Sb/ZnS@C hybrid heterostructures composed of Sb/ZnS inner core and
      carbon outer shell are rationally designed based on a robust template of ZnS
      nanosphere, as anodes for high-performance sodium-ion batteries (SIBs). A partial
      cation exchange reaction based on the solubility difference between Sb2 S3 and
      ZnS can transform mesoporous ZnS to Sb2 S3 /ZnS heterostructure. To get a stable
      structure, a thin contiguous resorcinol-formaldehyde (RF) layer is introduced on
      the surface of Sb2 S3 /ZnS heterostructure. The effectively protective carbon
      layer from RF can be designed as the reducing agent to convert Sb2 S3 to metallic
      Sb to obtain core-shell Sb/ZnS@C hybrid heterostructures. Simultaneously, the
      carbon outer shell is beneficial to the charge transfer kinetics, and can
      maintain the structure stability during the repeated sodiation/desodiation
      process. Owing to its unique stable architecture and synergistic effects between
      the components, the core-shell porous Sb/ZnS@C hybrid heterostructure SIB anode
      shows a high reversible capacity, good rate capability, and excellent cycling
      stability by turning the optimized voltage range. This novel strategy to prepare
      carbon-layer-protected metal/metal sulfide core-shell heterostructure can be
      further extended to design other novel nanostructured systems for high
      performance energy storage devices.

PMID- 29575526
TI  - Fatty Acid Amide Hydrolase Inhibition by JNJ-42165279: A Multiple-Ascending Dose
      and a Positron Emission Tomography Study in Healthy Volunteers.
AB  - Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid
      activity and is hypothesized to have therapeutic potential for mood and anxiety
      disorders and pain. The clinical profile of JNJ-42165279, an oral selective FAAH
      inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics,
      safety, and binding to FAAH in the brain of healthy human volunteers.
      Concentrations of JNJ-42165279 (plasma, cerebrospinal fluid (CSF), urine) and
      fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was
      determined in a phase I multiple ascending dose study. A positron emission
      tomography study with the FAAH tracer [11 C]MK3168 was conducted to determine
      brain FAAH occupancy after single and multiple doses of JNJ-42165279. JNJ
      42165279 administration resulted in an increase in plasma and CSF FAA.
      Significant blocking of brain FAAH binding of [11 C]MK3168 was observed after
      pretreatment with JNJ-42165279. JNJ-42165279 produces potent central and
      peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with
      doses >=10 mg of JNJ-42165279. No safety concerns were identified.

PMID- 29575527
TI  - Inhibition of yes-associated protein suppresses brain metastasis of human lung
      adenocarcinoma in a murine model.
AB  - Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes
      cancer development and progression in human lung cancer. We sought to determine
      whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a
      murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C
      mutation) and PC9-BrM3 (EGFRDeltaexon19 mutation) had a significantly decreased p
      YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9
      (EGFRDeltaexon19 mutation) cells (P < .05). H2030-BrM3 cells had significantly
      increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61
      compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin
      RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA
      expression in downstream genes CTGF and CYR61 in H2030-BrM3 cells (P < .05). In
      addition, inhibiting YAP by YAP shRNA significantly decreased migration and
      invasion abilities of H2030-BrM3 cells (P < .05). We are first to show that mice
      inoculated with YAP shRNA-transfected H2030-BrM3 cells had significantly
      decreased metastatic tumour burden and survived longer than control mice (P <
      .05). Collectively, our results suggest that YAP plays an important role in
      promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP
      by shRNA suppresses H2030-BrM3 cell brain metastasis in a murine model.

PMID- 29575528
TI  - Global remodeling of the mouse DNA methylome during aging and in response to
      calorie restriction.
AB  - Aging is characterized by numerous molecular changes, such as accumulation of
      molecular damage and altered gene expression, many of which are linked to DNA
      methylation. Here, we characterize the blood DNA methylome across 16 age groups
      of mice and report numerous global, region- and site-specific features, as well
      as the associated dynamics of methylation changes. Transition of the methylome
      throughout lifespan was not uniform, with many sites showing accelerated changes
      in late life. The associated genes and promoters were enriched for aging-related
      pathways, pointing to a fundamental link between DNA methylation and control of
      the aging process. Calorie restriction both shifted the overall methylation
      pattern and was accompanied by its gradual age-related remodeling, the latter
      contributing to the lifespan-extending effect. With age, both highly and poorly
      methylated sites trended toward intermediate levels, and aging was accompanied by
      an accelerated increase in entropy, consistent with damage accumulation. However,
      the entropy effects differed for the sites that increased, decreased and did not
      change methylation with age. Many sites trailed behind, whereas some followed or
      even exceeded the entropy trajectory and altered the developmental DNA
      methylation pattern. The patterns we observed in certain genomic regions were
      conserved between humans and mice, suggesting common principles of functional DNA
      methylome remodeling and its critical role in aging. The highly resolved DNA
      methylome remodeling provides an excellent model for understanding systemic
      changes that characterize the aging process.

PMID- 29575530
TI  - Novel Application of the Two-Period Microtracer Approach to Determine Absolute
      Oral Bioavailability and Fraction Absorbed of Ertugliflozin.
AB  - Ertugliflozin, a sodium glucose cotransporter-2 inhibitor, is approved in the
      United States for treatment of type 2 diabetes mellitus. A novel two-period study
      design with 14 C microtracer dosing in each period was used to determine absolute
      oral bioavailability (F) and fraction absorbed (Fa ) of ertugliflozin. Eight
      healthy adult men received 100-MUg i.v. 14 C-ertugliflozin (400 nCi) dose 1 h
      after a 15-mg oral unlabeled ertugliflozin dose (period 1), followed by 100 MUg
      14 C-ertugliflozin orally along with 15 mg oral unlabeled ertugliflozin (period
      2). Unlabeled ertugliflozin plasma concentrations were determined using high
      performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). 14 C
      ertugliflozin plasma concentrations were determined using HPLC-accelerator mass
      spectrometry (AMS) and 14 C urine concentrations were determined using AMS. F
      ((area under the curve (AUC)p.o. /14 C-AUCi.v. )*(14 C-Dosei.v. /Dosep.o. )) and
      Fa ((14 C_Total_Urinep.o. /14 C_Total_Urinei.v. )* (14 C-Dosei.v. /14 C-Dosep.o.
      )) were estimated. Estimates of F and Fa were 105% and 111%, respectively. Oral
      absorption of ertugliflozin was complete under fasted conditions and F was ~100%.
      Ertugliflozin was well tolerated.

PMID- 29575529
TI  - Podoplanin: An emerging cancer biomarker and therapeutic target.
AB  - Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on
      transformed cells, cancer associated fibroblasts and inflammatory macrophages
      that contribute to cancer progression. In particular, PDPN increases tumor cell
      clonal capacity, epithelial mesenchymal transition, migration, invasion,
      metastasis and inflammation. Antibodies, CAR-T cells, biologics and synthetic
      compounds that target PDPN can inhibit cancer progression and septic inflammation
      in preclinical models. This review describes recent advances in how PDPN may be
      used as a biomarker and therapeutic target for many types of cancer, including
      glioma, squamous cell carcinoma, mesothelioma and melanoma.

PMID- 29575531
TI  - Metabolic potential and in situ transcriptomic profiles of previously
      uncharacterized key microbial groups involved in coupled carbon, nitrogen and
      sulfur cycling in anoxic marine zones.
AB  - Anoxic marine zones (AMZs) impact biogeochemical cycles at the global scale,
      particularly the nitrogen cycle. Key microbial players from AMZs have been
      identified, but the majority remains unrecognized or uncharacterized. Thirty-one
      single-cell amplified genomes (SAGs) from the eastern tropical North and South
      Pacific AMZs were sequenced to gain insight into the distribution, metabolic
      potential and contribution to the community transcriptional profile of these
      uncharacterized bacterial and archaeal groups. Detailed analyses focused on SAG
      bins assigned to three of these groups that presented 79%-100% estimated genome
      completeness: the putative sulphur-oxidizing Gamaproteobacteria EOSA II clade, a
      Marinimicrobia member of the recently recognized PN262000N21 clade found to be
      abundant in AMZ anoxic cores, and a representative of the Marine Benthic Group A
      Thaumarchaeota. Community-based analyses revealed that these three groups are
      significantly more abundant and transcriptionally more active in the AMZ
      microbial communities than previously described phylogenetically related
      microbial groups. Collectively, these groups have the potential to link
      biogeochemically relevant processes by coupling the carbon, nitrogen and sulfur
      cycles. Together, these results increase our understanding of key microbial
      components inhabiting AMZs and other oxygen-deficient marine environments,
      enhancing our capacity to predict the impact of the expansion of these ecosystems
      due to climate change.

PMID- 29575532
TI  - Printing 1D Assembly Array of Single Particle Resolution for Magnetosensing.
AB  - Magnetosensing is a ubiquitous ability for many organism species in nature. 1D
      assembly, especially that arranged in single-particle-resolution regulation, is
      able to sense the direction of magnetic field depending on the enhanced dipolar
      interaction in the linear orientation. Inspired by the magnetosome structure in
      magnetotactic bacteria, a 1D assembly array of single particle resolution with
      controlled length and well-behaved configuration is prepared via inkjet printing
      method assisted with magnetic guiding. In the fabrication process, chains in a
      "tip-to-tip" regulation with the desired number of particles are prepared in a
      confined tiny inkjet-printed droplet. By adjusting the receding angle of the
      substrate, the assembled 1D morphology is kept/deteriorated depending on the
      pinning/depinning behavior during ink evaporation, which leads to the formation
      of well-behaved 1D assembly/aggregated dot assembly. Owing to the high-aspect
      ratio characteristic of the assembled structure, the as-prepared 1D arrays can be
      used for magnetic field sensing with anisotropic magnetization M// /M? up to
      6.03.

PMID- 29575533
TI  - Indyllithium and the Indyl Anion [InL]- : Heavy Analogues of N-Heterocyclic
      Carbenes.
AB  - Reduction of the indate complex In(NONAr )(MU-Cl)2 Li(OEt2 )2 (NONAr =[O(SiMe2
      NAr)2 ]2- ; Ar=2,6-iPr2 C6 H3 ) with sodium generates the InII diindane species
      [In(NONAr )]2 . Further reduction with a mixture of potassium and [2.2.2]crypt
      affords the InI N-heterocyclic indyl anion [In(NONAr )]- , which crystallizes
      with a non-contacted [K([2.2.2]crypt)]+ cation. The indyl anion can also be
      isolated as the indyllithium compound In(NONAr )(Li{THF}3 ), which contains an In
      Li bond. Density functional theory calculations show that the HOMO of the indyl
      anion is a metal-centred lone pair, and preliminary reactivity studies confirm
      its nucleophilic behaviour.

PMID- 29575534
TI  - Perioperative management of children with glycogen storage disease type II-Pompe
      disease.
AB  - BACKGROUND: Pompe disease is a rare metabolic disorder caused by a deficiency of
      the lysosomal enzyme acid alpha-glucosidase. Glycogen accumulation damages
      skeletal, cardiac, and smooth muscles, causing a progressive and debilitating
      muscle weakness and cardiomyopathy. As life expectancy has much improved since
      the introduction of enzyme replacement therapy an increasing number of patients
      are referred for surgical procedures. Due to the potential cardiopulmonary
      complications, these patients form a high-risk group for the anesthesiologist.
      AIMS: In this study, we investigated the incidence of perioperative complications
      in children with Pompe disease treated in our hospital since the introduction of
      enzyme replacement therapy. METHODS: Anesthetic and perioperative data of
      children with Pompe disease treated between 1999 and 2015 in the Erasmus MC
      Sophia Children's Hospital, University Medical Centre, Rotterdam, The
      Netherlands, were collected, retrospectively. RESULTS: Of the 65 children with
      Pompe disease, 34 patients underwent in total 77, mostly low-risk, surgical
      procedures. Twenty-one children had the classic infantile form and 13 had a
      nonclassic presentation of Pompe disease. In 13 (16.8%) procedures, 1 or more
      perioperative complications occurred. Perioperative desaturation was the main
      complication (12.9%), followed by arrhythmia (3.8%) and heart failure requiring
      diuretic treatment (2.6%). One child died 2 days postoperatively, but this was
      considered unrelated to the procedure. CONCLUSION: Despite the potentially high
      anesthetic risk for children with Pompe disease under enzyme replacement therapy,
      the incidence of perioperative complications in our study was relatively low. Our
      data suggest that with proper precautionary measures and a critical choice of
      timing of the operation, general anesthesia in children with Pompe disease could
      be relatively safe nowadays.

PMID- 29575535
TI  - Inhibition of yes-associated protein down-regulates PD-L1 (CD274) expression in
      human malignant pleural mesothelioma.
AB  - Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker
      in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the
      regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP),
      an important oncogenic protein in Hippo signalling pathway, reportedly promotes
      cancer development. We investigated whether inhibition of YAP down-regulates PD
      L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed
      that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein
      expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1
      mRNA expression was significantly increased compared to other MPM cell lines; YAP
      knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression.
      Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452
      cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD
      L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells.
      We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently
      expressed in immunohistochemistry stain (n = 70, P < .05, chi-square). We
      conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down
      regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1
      in MPM is warranted.

PMID- 29575537
TI  - Ready, willing and able: the role of pharmacists in natural and manmade disasters
      - can we do more?

PMID- 29575536
TI  - Mutation analysis of adenomas and carcinomas of the colon: Early and late
      drivers.
AB  - Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed
      in the US. We used whole exome sequence data from triplet samples (colon
      carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene
      mutation rates. Of the 2 204 genes that were mutated, APC, TTN, TP53, KRAS,
      OBSCN, SOX9, PCDH17, SIGLEC10, MYH6, and BRD9 were consistent with genes being an
      early driver of carcinogenesis, in that they were mutated in multiple adenomas
      and multiple carcinomas. Fifty-two genes were mutated in >=12.5% of
      microsatellite stable (MSS) carcinomas but not in any of the adenomas, in line
      with the profile of a late driver event involved in tumor progression. Thirty
      eight genes were sequenced in a larger independent set of 148 carcinoma/normal
      tissue pairs to obtain more precise mutation frequencies. Eight of the genes,
      APC, TP53, ATM, CSMD3, LRP1B, RYR2, BIRC6, and MUC17, contained mutations in >20%
      of the carcinomas. Interestingly, mutations in four genes in addition to APC that
      are associated with dysregulation of Wnt signaling, were all classified as early
      driver events. Most of the genes that are commonly associated with colon cancer,
      including APC, TP53, and KRAS, were all classified as being early driver genes
      being mutated in both adenomas and carcinomas. Classifying genes as potential
      early and late driver events points to candidate genes that may help dissect
      pathways involved in both tumor initiation and progression.

PMID- 29575538
TI  - Global use and misuse of opioids.

PMID- 29575539
TI  - Healthcare providers' perspectives on perceived barriers and facilitators of
      compassion: Results from a grounded theory study.
AB  - AIMS AND OBJECTIVES: To explore healthcare provider perspectives and experiences
      of perceived barriers and facilitators of compassion. BACKGROUND: Compassion is
      considered a component of quality health care that healthcare providers are
      increasingly expected to provide. While there have been some studies exploring
      facets of healthcare providers' perspectives on the barriers and facilitators to
      providing compassion, a comprehensive understanding based on direct reports from
      healthcare providers is lacking. DESIGN: Data were collected via focus groups and
      semi-structured interviews. Data was analyzed in accordance with Straussian
      grounded theory. METHODS: Semistructured focus groups with frontline healthcare
      providers and individual interviews with peer-nominated exemplary compassionate
      care providers were audio-recorded, professionally transcribed and analysed.
      Fifty-seven participants were recruited from three healthcare settings within
      both rural and urban settings in Alberta, Canada, using convenience, snowball and
      theoretical sampling. RESULTS: Qualitative analysis of the data generated two
      categories and associated themes and subthemes delineating perceived barriers and
      facilitators to compassion. The first category, challenges to compassion,
      reflects participants' discomfort associating the notion of barriers to
      compassion and contained several themes participants conceptualised as
      challenges: personal challenges, relational challenges, systemic challenges and
      maladaptive responses. The second category, facilitators of compassion, included
      the themes of personal facilitators, relational facilitators, systemic
      facilitators and adaptive responses of intentional action. CONCLUSION: Although
      participants described certain factors such as system and time constraints along
      with interaction styles of patients and families that can challenge healthcare
      provider compassion, these challenges were not considered insurmountable. While
      acknowledging these as challenges, participants identified healthcare providers
      themselves, including their responses towards the identified challenges of
      compassion, as significant factors in this process-a novel finding from this
      study. This study provides insight into healthcare providers' perspectives on the
      notion of barriers and facilitators in the provision of compassion. RELEVANCE TO
      CLINICAL PRACTICE: This study provides a blueprint for optimising compassion on a
      personal, relational and system level.

PMID- 29575540
TI  - Genomewide mechanisms of chronological longevity by dietary restriction in
      budding yeast.
AB  - Dietary restriction is arguably the most promising nonpharmacological
      intervention to extend human life and health span. Yet, only few genetic
      regulators mediating the cellular response to dietary restriction are known, and
      the question remains which other regulatory factors are involved. Here, we
      measured at the genomewide level the chronological lifespan of Saccharomyces
      cerevisiae gene deletion strains under two nitrogen source regimens, glutamine
      (nonrestricted) and gamma-aminobutyric acid (restricted). We identified 473
      mutants with diminished or enhanced extension of lifespan. Functional analysis of
      such dietary restriction genes revealed novel processes underlying longevity by
      the nitrogen source quality, which also allowed us to generate a prioritized
      catalogue of transcription factors orchestrating the dietary restriction
      response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1,
      and Ste12 resulted in diminished lifespan extension and defects in cell cycle
      arrest upon nutrient starvation, suggesting that regulation of the cell cycle is
      a major mechanism of chronological longevity. We further show that STE12
      overexpression is enough to extend lifespan, linking the pheromone/invasive
      growth pathway with cell survivorship. Our global picture of the genetic players
      of longevity by dietary restriction highlights intricate regulatory cross-talks
      in aging cells.

PMID- 29575541
TI  - Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia
      chromosome-positive acute lymphoblastic leukemia using a customized target
      enrichment system panel.
AB  - INTRODUCTION: Recent clinical outcomes of pediatric Philadelphia chromosome
      positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine
      kinase inhibitor (TKI). However, the genetic status would be different in each
      case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1
      deletion. In particular, the TKI resistant clone with ABL1 kinase mutation
      remains problematic. The comprehensive assessment of genetic status including
      mutation, insertion and deletion (indel) and CNVs is necessary. METHODS: We
      evaluated a next-generation sequencing (NGS)-based customized HaloPlex target
      enrichment system panel to simultaneously detect coding mutations, indel and
      CNVs. We analysed approximately 160 known genes associated with hematological
      disorders in 5 pediatric Ph+ALL patients. RESULTS: Mono-allelic IKZF1 deletions
      were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions
      were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were
      detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected
      in 1 patient at relapse. These results were almost comparable with the results of
      the multiplex ligation-dependent probe amplification (MLPA) method or Sanger
      sequence. CONCLUSION: Next-generation sequencing-based custom HaloPlex target
      enrichment system panel allows us to detect the coding mutations, indel, and CNVs
      in pediatric Ph+ALL simultaneously, and its results seem comparable with those of
      other methods.

PMID- 29575542
TI  - The stressed brain of humans and rodents.
AB  - After stress, the brain is exposed to waves of stress mediators, including
      corticosterone (in rodents) and cortisol (in humans). Corticosteroid hormones
      affect neuronal physiology in two time-domains: rapid, non-genomic actions
      primarily via mineralocorticoid receptors; and delayed genomic effects via
      glucocorticoid receptors. In parallel, cognitive processing is affected by stress
      hormones. Directly after stress, emotional behaviour involving the amygdala is
      strongly facilitated with cognitively a strong emphasis on the "now" and "self,"
      at the cost of higher cognitive processing. This enables the organism to quickly
      and adequately respond to the situation at hand. Several hours later, emotional
      circuits are dampened while functions related to the prefrontal cortex and
      hippocampus are promoted. This allows the individual to rationalize the stressful
      event and place it in the right context, which is beneficial in the long run. The
      brain's response to stress depends on an individual's genetic background in
      interaction with life events. Studies in rodents point to the possibility to
      prevent or reverse long-term consequences of early life adversity on cognitive
      processing, by normalizing the balance between the two receptor types for
      corticosteroid hormones at a critical moment just before the onset of puberty.

PMID- 29575543
TI  - Identifying Off-Label Prescriptions Through Data Mining in Danish Community
      Pharmacy Servers: An Exploratory Study on Desmopressin, Diclofenac, Fucidin,
      Mirtazapine and Quetiapine.
AB  - The term off-label use describes the prescription and administration of medicines
      outside of the terms for which it officially has been approved, including age,
      dose and indication. Off-label data can be generated from the Danish National
      Prescription Registry through combinations with diagnoses; however, the community
      pharmacy servers provide equal, local, albeit less data through a faster and less
      constrained collection process. The data collection for this exploratory study
      took place at five community pharmacies in Denmark. Five drugs were chosen for
      the investigation and collection of prescription data across a 2-year period. Off
      label use by age was observed to be 1.9% for diclofenac, 1.7% for desmopressin
      and 2.3% for quetiapine. The percentages were based on total number of 3881, 925,
      2712 prescriptions, respectively. Off-label monitored by dosage appeared to be
      75% for quetiapine; by box label text analysis, off-label indication was found to
      be 10-15% and 15-23% for quetiapine and mirtazapine (from a total number of 3178
      prescriptions), respectively. By route of administration where fucidin ointment
      was applied to the nose in 60 patients, 83% were prescribed off-label (non
      dermatological). This exploratory study revealed that pharmacy servers represent
      a reliable and up-to-date source to collect a substantial amount of raw
      prescription data. The method gives straightforward and simple access to analysis
      of off-label use by age and dose, whereas it is possible but difficult to
      interpret off-label indications and route of administration from the box label
      text.

PMID- 29575544
TI  - Adverse reactions of sorafenib, sunitinib, and imatinib in treating digestive
      system tumors.
AB  - BACKGROUND: This study was conducted to assess the adverse reactions caused by
      multi-target tyrosine kinase inhibitor treatment of gastrointestinal tumors.
      METHODS: We carried out a retrospective study of drug-related adverse reactions
      in 115 patients who were treated with sorafenib, sunitinib, and imatinib for
      primary hepatocellular carcinoma or gastrointestinal stromal tumors from October
      2003 to March 2012 at the Peking University International Hospital. RESULTS: The
      total incidence of adverse reactions of sorafenib, sunitinib, and imatinib in
      patients with hepatocellular carcinoma and gastrointestinal stromal tumors was >
      80%. The main adverse reactions of sorafenib were hypertension in 38 patients
      (33.3%) and diarrhea in 28 patients (24.4%). Sunitinib was associated with higher
      incidence and greater grade 3-4 toxicity. The common toxicities were skin color
      changes in 105 patients (90.9%), hand-foot skin reactions in 65 patients (54.6%),
      and leukopenia (63.6%), hypertension (22.7%), proteinuria (22.7%), liver function
      impairment (22.7%), and hypomagnesemia (27.3%). While imatinib was well
      tolerated, it was associated with the highest number of adverse reactions,
      including skin color change (55.6%) and edema (38.9%). Hypophosphatemia (4.4%)
      and hoarseness (2.2%) only occurred in the sorafenib treatment group.
      CONCLUSIONS: The adverse reactions of multi-target tyrosine kinase inhibitor
      treatments are generally mild to moderate, and most patients can tolerate these
      without the need for further intervention. Some serious adverse reactions may be
      alleviated by discontinuing the drugs or by administering symptomatic treatment.

PMID- 29575546
TI  - Repurposing existing medications in oncology and their potential role in oral
      cancer.

PMID- 29575545
TI  - Two soybean bHLH factors regulate response to iron deficiency.
AB  - Iron is an indispensable micronutrient for plant growth and development. Limited
      bioavailability of Fe in the soil leads to iron deficiency chlorosis in plants
      and yield loss. In this study, two soybean basic helix-loop-helix transcription
      factors, GmbHLH57 and GmbHLH300, were identified in response to Fe-deficiency.
      Both transcription factors are expressed in roots and nodules, and are induced by
      Fe deficiency; these patterns were confirmed in transgenic hairy roots expressing
      constructs of the endogenous promoters fused to a GUS reporter gene. Bimolecular
      fluorescence complementation, yeast two-hybrid and coimmunoprecipitation (co-IP)
      assays indicated a physical interaction between GmbHLH57 and GmbHLH300. Studies
      on transgenic soybeans overexpressing GmbHLH57 and GmbHLH300 revealed that
      overexpression of each transcription factor, alone, results in no change of the
      responses to Fe deficiency, whereas overexpression of both transcription factors
      upregulated the downstream Fe uptake genes and increased the Fe content in these
      transgenic plants. Compared to wild type, these double overexpression transgenic
      plants were more tolerant to Fe deficiency. Taken together, our findings
      establish that GmbHLH57 and GmbHLH300 are important transcription factors
      involved in Fe homeostasis in soybean.

PMID- 29575547
TI  - Guided maxillary sinus floor elevation using deproteinized bovine bone versus
      graftless Schneiderian membrane elevation with simultaneous implant placement:
      Randomized clinical trial.
AB  - OBJECTIVE: The aim of this study is to evaluate the analytical difference between
      the use of xenograft (control group) and graftless tenting (test group) technique
      after sinus lift procedure with simultaneous implant placement. MATERIALS AND
      METHODS: Seventeen patients and 20 sinuses where operated for sinus lift
      procedures using lateral window approach with simultaneous implant placement.
      Deproteinized bovine bone (Xenograft) was used as a filling material in control
      group while nongrafted sinus lifting was performed in the test group. Multislice
      CT was obtained preoperatively and CBCT were obtained immediately postoperative
      and 6 months after operation. Osstell readings were taken at the time of implant
      placement and implant exposure (6 months) RESULTS: Mean bone height gain in the
      xenograft group was 8.59 +/- 0.74 while that of the tenting group was 4.85 +/-
      0.5 and it was statistically significant (P < .05). Mean bone density values in
      the xenograft group was 375.59 +/- 49.38 while that of the tenting group was
      269.08 +/- 16.27 and it was statistically significant (P < .05). Mean ISQ values
      for the xenograft group was 78.3 +/- 5.08 while that of the tenting group was 74
      +/- 3.19 and it was statistically significant (P < .05). CONCLUSIONS: Within the
      limitation of this study, sinus lift procedures with simultaneous implant
      placement using xenograft as a filling material or graftless technique are
      considered reliable procedures, however, the use of xenograft provide better
      results in all aspects regarding (bone height gain, bone density, and implant
      stability).

PMID- 29575549
TI  - Role of artemin in non-small cell lung cancer.
AB  - BACKGROUND: In this study, we investigated the role of artemin, a member of the
      glial cell-derived neurotrophic factor of ligands, in the malignant phenotype of
      lung cancer. METHODS: Artemin expression was examined in various types of lung
      cancer and normal lung tissues, as well as in lung cancer cell lines by
      immunohistochemistry and semi-quantitative PCR. Functional studies were performed
      using artemin overexpression or knockdown vectors in lung cancer cell lines.
      Methyl thiazolyl tetrazolium, flow cytometry, wound healing, and transwell assays
      were conducted to evaluate the contribution of artemin on tumor cell
      proliferation, migration, and invasion. RESULTS: Artemin is broadly expressed in
      lung cancer tissues, and is associated with tumor staging. Overexpression of
      artemin in NL9980 large cell lung cancer cells increased proliferating cells and
      enhanced migrating capability in wound healing and transwell assays, as well as
      demonstrating enhanced invasion capability. Silencing artemin in LTEP-alpha-2
      adenocarcinoma cell lines decreased cellular proliferation, migration, and
      invasion capabilities. CONCLUSION: Artemin could promote the proliferation and
      invasiveness of lung cancer cells in vitro and therefore could be a new potential
      target to combat lung cancer.

PMID- 29575548
TI  - Evidence that miR-146a attenuates aging- and trauma-induced osteoarthritis by
      inhibiting Notch1, IL-6, and IL-1 mediated catabolism.
AB  - Primary osteoarthritis (OA) is associated with aging, while post-traumatic OA
      (PTOA) is associated with mechanical injury and inflammation. It is not clear
      whether the two types of osteoarthritis share common mechanisms. We found that
      miR-146a, a microRNA-associated with inflammation, is activated by cyclic load in
      the physiological range but suppressed by mechanical overload in human articular
      chondrocytes. Furthermore, miR-146a expression is decreased in the OA lesions of
      human articular cartilage. To understand the role of miR-146a in osteoarthritis,
      we systemically characterized mice in which miR-146a is either deficient in whole
      body or overexpressed in chondrogenic cells specifically. miR-146a-deficient mice
      develop early onset of OA characterized by cartilage degeneration, synovitis, and
      osteophytes. Conversely, miR-146a chondrogenic overexpressing mice are resistant
      to aging-associated OA. Loss of miR-146a exacerbates articular cartilage
      degeneration during PTOA, while chondrogenic overexpression of miR-146a inhibits
      PTOA. Thus, miR-146a inhibits both OA and PTOA in mice, suggesting a common
      protective mechanism initiated by miR-146a. miR-146a suppresses IL-1beta of
      catabolic factors, and we provide evidence that miR-146a directly inhibits Notch1
      expression. Therefore, such inhibition of Notch1 may explain suppression of
      inflammatory mediators by miR-146a. Chondrogenic overexpression of miR-146a or
      intra-articular administration of a Notch1 inhibitor alleviates IL-1beta-induced
      catabolism and rescues joint degeneration in miR-146a-deficient mice, suggesting
      that miR-146a is sufficient to protect OA pathogenesis by inhibiting Notch
      signaling in the joint. Thus, miR-146a may be used to counter both aging
      associated OA and mechanical injury-/inflammation-induced PTOA.

PMID- 29575550
TI  - Understanding the current sexual health service provision for mental health
      consumers by nurses in mental health settings: Findings from a Survey in
      Australia and England.
AB  - Nurses in mental health settings avoid talking to consumers about sexual health
      concerns. It is unclear whether this avoidance prevents the provision of sexual
      healthcare. The present study gathered information about how mental health nurses
      respond to sexual health issues within their routine practice, what issues they
      address, and their view on their role in promoting sexual health for consumers. A
      cross-sectional study using an electronic survey questionnaire, originally
      generated from a previous study in the united kingdom, was employed. The study
      occurred in four National Health Service Trusts in England and a national call
      for participants in Australia. Participants were nurse clinicians (n = 303) who
      self-selected by completing surveys available via email and newsletters
      containing links to the survey. The results demonstrated that mental health
      nurses do not routinely include sexual health in their practice and are poorly
      prepared in knowing what to do with a sexual health issue, and what services to
      assist consumers to use. In conclusion, it has been well established in the
      literature that mental health consumers experience high sexual health needs that
      potentially impact on health and recovery. Mental health nurses are ideally
      placed to promote sexual health and refer consumers to sexual health and family
      planning services. Training to improve the confidence and responsiveness of
      mental health nurses to sexual health is an urgent need.

PMID- 29575551
TI  - A 28-day Sub-acute Genotoxic and Behavioural Assessment of Garcinielliptone FC.
AB  - Garcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from
      Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties.
      However, its safe use and other effects on the central nervous system require
      assessment. This study assessed the toxicological effects of GFC using the comet
      assay and the micronucleus test in mice treated for 28 days. A behavioural model
      was employed to detect possible injuries on the central nervous system. Mice
      treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to
      rotarod test, open-field test and tail suspension test (TST). After the behaviour
      tasks, biological samples were assessed to evaluate genotoxic and mutagenic
      effects using the comet assay and the micronucleus test. Garcinielliptone FC did
      not impair the performance of the animals in the rotarod and open-field tests,
      with no antidepressant-like effect in TST. No genotoxic effects in blood and
      cerebral cortex were observable in the comet assay; however, there was a
      significant increase in index and frequency of damage in liver after treatment
      with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in
      bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce
      genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was
      caused only by the highest dose, although no mutagenic potential was observed.

PMID- 29575552
TI  - Reef invertebrate viromics: diversity, host specificity and functional capacity.
AB  - Recent metagenomic analyses have revealed a high diversity of viruses in the
      pelagic ocean and uncovered clear habitat-specific viral distribution patterns.
      Conversely, similar insights into the composition, host specificity and function
      of viruses associated with marine organisms have been limited by challenges
      associated with sampling and computational analysis. Here, we performed targeted
      viromic analysis of six coral reef invertebrate species and their surrounding
      seawater to deliver taxonomic and functional profiles of viruses associated with
      reef organisms. Sponges and corals' host species-specific viral assemblages with
      low sequence identity to known viral genomes. While core viral genes involved in
      capsid formation, tail structure and infection mechanisms were observed across
      all reef samples, auxiliary genes including those involved in herbicide
      resistance and viral pathogenesis pathways such as host immune suppression were
      differentially enriched in reef hosts. Utilising a novel OTU based assessment, we
      also show a prevalence of dsDNA viruses belonging to the Mimiviridae,
      Caudovirales and Phycodnaviridae in reef environments and further highlight the
      abundance of ssDNA viruses belonging to the Circoviridae, Parvoviridae,
      Bidnaviridae and Microviridae in reef invertebrates. These insights into coral
      reef viruses provide an important framework for future research into how viruses
      contribute to the health and evolution of reef organisms.

PMID- 29575553
TI  - JCD Editorial-April, 2018.

PMID- 29575554
TI  - Atmospheric skin aging-Contributors and inhibitors.
AB  - Cutaneous aging is a complex biological process consisting of 2 elements:
      intrinsic aging, which is primarily determined by genetics, and extrinsic aging,
      which is largely caused by atmospheric factors, such as exposure to sunlight and
      air pollution, and lifestyle choices, such as diet and smoking. The role of the
      solar spectrum, comprised of ultraviolet light, specifically UVB (290-320 nm) and
      UVA (320-400) in causing skin damage, including skin cancers, has been well
      documented. In recent years, the contribution of visible light (400-700 nm) and
      infrared radiation (above 800 nm) in causing skin damage, similar to the
      photodamage caused by UV light, is also being elucidated. In addition, other
      atmospheric factors such as air pollution (smog, ozone, particulate matter, etc.)
      have been implicated in premature skin aging. The skin damage caused by
      environmental exposure is largely attributable to a complex cascade of reactions
      inside the skin initiated by the generation of reactive oxygen species (ROS),
      which causes oxidative damage to cellular components such as proteins, lipids,
      and nucleic acids. These damaged skin cells initiate inflammatory responses
      leading to the eventual damage manifested in chronically exposed skin. Novel
      therapeutic strategies to combat ROS species generation are being developed to
      prevent the skin damage caused by atmospheric factors. In addition to protecting
      skin from solar radiation using sunscreens, other approaches using topically
      applied ingredients, particularly antioxidants that penetrate the skin and
      protect the skin from within, have also been well documented. This review
      summarizes current knowledge of atmospheric aggressors, including UVA, UVB,
      visible light, infrared radiation (IR), and ozone on skin damage, and proposes
      new avenues for future research in the prevention and treatment of premature skin
      aging caused by such atmospheric factors. New therapeutic modalities currently
      being developed are also discussed.

PMID- 29575555
TI  - In vitro and in vivo effects of a novel bioactive glass-based cement used as a
      direct pulp capping agent.
AB  - Direct pulp capping is an important procedure for preserving pulp viability. The
      pulp capping agent must possess several properties, including usability,
      biocompatibility, and the ability to induce reparative dentin formation. In this
      study, a novel bioactive glass-based cement was examined to determine whether the
      cement has the necessary properties to act as a direct pulp capping agent.
      Physicochemical properties of the bioactive glass-based cement and in vitro
      effects of the cement on odontoblast-like cells, as well as in vivo effects on
      the exposed dental pulp, were analyzed. The cement immersed in water stabilized
      at pH10, and hydroxyapatite-like precipitation was induced on the surface of the
      cement in simulate body fluid. There were no cytotoxic effects on the viability,
      alkaline phosphatase activity, or calcium deposition ability of odontoblast-like
      cells. In the in vivo rat study of an exposed dental pulp model, the cement
      induced a sufficient level of reparative dentin formation by odontoblast-like
      cells expressing odontoblastic markers at the exposed area of the dental pulp.
      These results suggest that the newly developed bioactive glass-based cement
      provides favorable biocompatibility with the dental pulp and may be useful as a
      direct pulp capping agent. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 2018.

PMID- 29575557
TI  - Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph
      node metastasis from papillary thyroid carcinoma.
AB  - OBJECTIVES: Ultrasound-guided aspiration cytology (US-FNAC) was previously used
      to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined
      US-FNAC with nodal thyroglobulin (LN-FNA-Tg) significantly improved the
      diagnostic rate. However, diagnostic accuracy depends on proper node selection.
      Therefore, it is crucial to choose the nodes with reliable sonographic features
      to guide clinician for confirmation. DESIGN AND SETTING: Retrospective cohort
      study was carried out in one medical centre from 2011 to 2014. PARTICIPANTS: A
      total of 148 patients with PTC, being treated by total thyroidectomy and
      radioiodine, were assessed for potential nodal metastases by ultrasound. MAIN
      OUTCOME MEASURES: Lymph nodes with cystic content, peripheral hypervascularity,
      calcification, hyperechoic content, the absence of hilum and Solbiati index < 2
      indicated risk of malignancy. US-FNAC and LN-FNA-Tg were both performed. Positive
      nodal metastasis was further confirmed by dissection. Risk impact of these
      sonographic features on LN-FNA-Tg to diagnose nodal metastasis was tested by
      logistic regression analysis based on the significance in both univariate and
      multivariate models. RESULTS: Overall, 49 lymph nodes were documented as
      recurrent nodal metastasis. LN-FNA-Tg greater than serum thyroglobulin and higher
      than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The
      malignant sonographic features that significantly cohered with positive LN-FNA-Tg
      were cystic and hyperechoic content and lack hilum, in sequence. CONCLUSIONS: LN
      FNA-Tg is an excellent tool to quantitatively diagnose nodal metastasis. To
      achieve ideal diagnosis, the most reliable sonographic features were cystic
      content, hyperechoic content and the absence of hilum in lymph nodes, but not
      calcification or Solbiati index < 2.

PMID- 29575556
TI  - Development of a vaccine based on bacteria-mimicking tumor cells coated with
      novel engineered toll-like receptor 2 ligands.
AB  - For a successful tumor vaccine, it is necessary to develop effective immuno
      adjuvants and identify specific tumor antigens. Tumor cells obtained from
      surgical or biopsy tissues are a good source of tumor antigens but, unlike
      bacteria, they do not induce strong immune responses. Here, we designed 2 novel
      lipopeptides that coat tumor cell surfaces and mimic bacterial components. Tumor
      cells coated with these lipopeptides (called bacteria-mimicking tumor cells
      [BMTC]) were prepared and their efficacy as a tumor vaccine examined. Natural
      bacterial lipopeptides act as ligands for toll-like receptor 2 (TLR2) and
      activate dendritic cells (DC). To increase the affinity of the developed
      lipopeptides for the negatively charged plasma membrane, a cationic polypeptide
      was connected to Pam2Cys (P2C), which is the basic structure of the TLR2 ligand.
      This increased the non-specific binding affinity of the peptides for the cell
      surface. Two such lipopeptides, P2CSK11 (containing 1 serine and 11 lysine
      residues) and P2CSR11 (containing 1 serine and 11 arginine residues) bound to
      irradiated tumor cells via the long cationic polypeptides more efficiently than
      the natural lipopeptide MALP2 (P2C-GNNDESNISFKEK) or a synthetic lipopeptide
      P2CSK4 (a short cationic polypeptide containing 1 serine and 4 lysines). BMTC
      coated with P2CSR11 or P2CSK11 were efficiently phagocytosed by DC and induced
      antigen cross-presentation in vitro. They also induced effective tumor-specific
      cytotoxic T cell responses and inhibited tumor growth in in vivo mouse models.
      P2CSR11 activated DC but induced less inflammation-inducing cytokines/interferons
      than other lipopeptides. Thus, P2CSR11 is a strong candidate antigen-specific
      immuno-adjuvant, with few adverse effects.

PMID- 29575558
TI  - Dispersing male Parnassius smintheus butterflies are more strongly affected by
      forest matrix than are females.
AB  - Dispersal is a central aspect of the ecology, evolution, and conservation of
      species. Predicting how species will respond to changing environmental conditions
      requires understanding factors that produce variation in dispersal. We explore
      one source of variation, differences between sexes within a spatial population
      network. Here, we compare the dispersal patterns of male and female Parnassius
      smintheus among 18 subpopulations over 8 years using the Virtual Migration Model.
      Estimated dispersal parameters differed between males and females, particularly
      with respect to movement through meadow and forest matrix habitat. The estimated
      dispersal distances of males through forest were much less than for females.
      Observations of female movement showed that, unlike males, females do not avoid
      forest nor does forest exert an edge effect. We explored whether further forest
      encroachment in this system would have different effects for males and females by
      fitting mean parameter estimates to the landscape configuration seen in 1993 and
      2012. Despite differences in their dispersal due presumably to both habitat and
      physiological differences, males and females are predicted to respond in similar
      ways to reduced meadow area and increased forest isolation.

PMID- 29575559
TI  - Renal nerve ablation reduces blood pressure in resistant hypertension: Long-term
      clinical outcomes in a single-center experience.
AB  - Approximately 10% of patients with hypertension have resistant hypertension, even
      if adequate pharmacological therapy is established. In this regard, renal nerve
      ablation (RNA) could represent a valid alternative treatment option. In a
      retrospective analysis with a follow-up of 6, 12, and 24 months, the authors
      investigated the efficacy and safety of catheter-based renal artery ablation in
      57 patients undergoing RNA with multiple renal nerve ablation in both renal
      arteries. In addition to medical antihypertensive therapy (4.2 +/- 1.4 drugs per
      patient), RNA using three different ablation systems was performed in patients
      with confirmed resistant hypertension (systolic blood pressure >140 mm Hg in
      spite of three drugs including a diuretic). The primary end point was the change
      in office ambulatory systolic blood pressure from baseline to 6, 12, and 24
      months of follow-up after RNA. The primary safety end point was the change in
      plasma creatinine levels after 12 and 24 months compared with baseline. The mean
      office systolic blood pressure at baseline was 167.6 +/- 22.4 and after 6, 12,
      and 24 months averaged 143.5 +/- 21.1 (P < .05), 141.1 +/- 21.1 (P < .05), and
      139.4 +/- 19.6 mm Hg (P < .05) respectively, with an average of 15.1 +/- 5.3
      nerve ablations performed. No significant changes in plasma creatinine levels
      were observed at 12 months (P = .421) and at 24 months (P = .217). There were no
      complications after RNA nor any relevant adverse vascular, renal, or
      cardiovascular events observed except in one patient in whom a covered stent had
      to be placed at the femoral puncture site. In this study, in all patients with
      resistant hypertension, RNA, if performed adequately in the number of ablations
      and energy delivery, is an efficient and safe treatment option to lower office
      and 24-hour blood pressure. Whether these blood pressure-lowering effects will
      lead to a reduction of cardiovascular morbidity and mortality will require
      further studies.

PMID- 29575561
TI  - Sex-specific functional adaptation of the femoral diaphysis to body composition.
AB  - OBJECTIVES: The human femoral diaphysis is often used to reconstruct loading
      histories (mobility, activity, body mass). The proximal femur is known to be
      differentially affected by changes in total fat-mass (FM), fat-free mass (FFM),
      and body fat percentage (BF%), but the adaptation of the entire diaphysis to body
      composition has not been thoroughly characterized to date. Understanding how the
      femoral diaphysis adapts to body components would benefit biomechanical
      interpretations of the femoral variation and nutrition-related studies. METHODS:
      Combining various methods from clinical nutrition, biological anthropology, and
      geometric morphometrics, we evaluated the correlation of measures taken on the
      entire femoral diaphysis with estimated FM, FFM, and BF% from 61 CT scans (17
      females, 44 males). The sample was predominantly composed of people with obesity.
      RESULTS: Cortical area of the cross-sections and local cortical thickness showed
      high correlation with BF% in particular, in females only. The curvature
      significantly decreased with FM and BF% in both sexes. The lowest correlations
      are found with FFM. CONCLUSIONS: The observed sexual dimorphism is consistent
      with differing aging processes; cortical bone decreases in females through
      endosteal resorption while it remains almost constant in males who compensate for
      endosteal resorption by periosteal apposition on the diaphyseal surface. The
      functional adaptation to compressive forces indicates a systemic endosteal
      apposition of bone material with increased BF% and FM in females only. FM and BF%
      are linked to a straighter femur in both sexes, suggesting an optimization of the
      resistance to compressive loads by distributing them more linearly along the
      entire diaphysis.

PMID- 29575560
TI  - Attempts to reduce alcohol intake and treatment needs among people with probable
      alcohol dependence in England: a general population survey.
AB  - AIMS: To compare the proportion of people in England with probable alcohol
      dependence [Alcohol Use Disorders Identification Test (AUDIT) score >= 20] with
      those with other drinking patterns (categorized by AUDIT scores) in terms of
      motivation to reduce drinking and use of alcohol support resources. DESIGN: A
      combination of random probability and simple quota sampling to conduct monthly
      cross-sectional household computer-assisted interviews between March 2014 and
      August 2017. SETTING: The general population in all nine regions of England.
      PARTICIPANTS: Participants in the Alcohol Toolkit Study (ATS), a monthly
      household survey of alcohol consumption among people aged 16 years and over in
      England (n = 69 826). The mean age was 47 years [standard deviation (SD) = 18.78;
      95% confidence interval (CI) = 46.8-47] and 51% (n = 35 560) were female.
      MEASUREMENTS: chi2 tests were used to investigate associations with demographic
      variables, motivation to quit drinking, attempts to quit drinking, general
      practitioner (GP) engagement and types of support accessed in the last 12 months
      across AUDIT risk zones. FINDINGS: A total of 0.6% were classified as people with
      probable alcohol dependence (95% CI = 0.5-0.7). Motivation to quit (chi2  =
      1692.27, P < 0.001), current attempts (chi2  = 473.94, P < 0.001) and past-year
      attempts (chi2  = 593.67, P < 0.001) differed by AUDIT risk zone. People with
      probable dependence were more likely than other ATS participants to have a past
      year attempt to cut down or quit (51.8%) and have received a specialist referral
      from their GP about drinking (13.7%), and less likely to report no motivation to
      reduce their drinking (26.2%). Those with probable dependence had higher use of
      self-help books and mobile applications (apps) than other ATS participants;
      however, 27.7% did not access any resources during their most recent attempt to
      cut down. CONCLUSIONS: Adults in England with probable alcohol dependence,
      measured through the Alcohol Use Disorders Identification Test, demonstrate
      higher motivation to quit drinking and greater use of both specialist treatment
      and self-driven support compared with those in other Alcohol Use Disorders
      Identification Test zones, but most do not access treatment resources to support
      their attempts.

PMID- 29575562
TI  - An evaluation of fetal heart rate characteristics associated with neonatal
      encephalopathy: a case-control study.
AB  - OBJECTIVE: We sought to identify fetal heart rate (FHR) characteristics that are
      associated with neonatal encephalopathy (NE). DESIGN: Retrospective case-control
      study. SETTING: A single medical centre in Shanghai, China, 2006-2015. SAMPLE:
      Women delivering a singleton, non-anomalous infant at >=36 weeks' gestation
      diagnosed with NE (cases, n = 109) were compared with a group of women with
      unaffected infants (controls, n = 233). METHODS: Two physicians blinded to the
      outcome independently reviewed FHR tracings during the last 30 minutes of tracing
      prior to delivery. FHR characteristics were compared in the two groups and
      multivariable logistic regression was used to adjust for confounding. MAIN
      OUTCOME MEASURES: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for
      the presence of specific FHR categories and characteristics. RESULTS: Category II
      FHR tracings were observed in 89% of women prior to delivery and were not
      independently associated with NE. Notably, a category III FHR was observed in
      17.4% of women in the NE group compared with 0.9% of women in the control group
      (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late
      decelerations and prolonged decelerations were independently associated with NE,
      whereas accelerations were protective. Similar findings were found when the cases
      were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women
      with category II tracings. CONCLUSIONS: Category III tracings, while infrequent,
      are not uncommon prior to delivery among fetuses who develop NE. In contrast,
      most FHR tracings are category II prior to delivery; however, individual FHR
      characteristics within this category are associated with NE. FUNDING: This
      research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong
      University. TWEETABLE ABSTRACT: Category III tracings are not uncommon prior to
      delivery among fetuses who develop neonatal encephalopathy.

PMID- 29575563
TI  - Orbito-frontal cortex mechanism of inhibition of return in current and remitted
      depression.
AB  - Deficient inhibition of return (IOR) for emotional materials is an important
      cognitive biomarker of depression. However, its neural mechanism and role in
      depression remission remain largely unknown. Using functional magnetic resonance
      imaging (fMRI), this study observed the neural foundation of inhibition of return
      in individuals with current (n = 30) and remitted (n = 27) depression and in
      healthy controls (n = 33), by using a cue-target task. The results showed that
      individuals with remitted depression (RMD) possessed a nonavoidant attention
      model for sad faces, which indicated a cue validity and was correlated with
      enhanced task- and resting-state activation and function connectivity in
      orbitofrontal cortex (OFC). The patients with major depressive disorder (MDD), in
      contrast, displayed an IOR effect for all faces, which indicated a strategy of
      attention avoidance due to the high cognitive burden in the cue-target task, and
      was correlated with decreased resting-state activation and function connectivity
      in OFC. Moreover, the hippocampus, a less-known cortex in IOR, showed a contrary
      model, that is, lower activation in depression remission and higher task- and
      resting-state activation in depressive episodes. The results suggest the OFC
      mechanism of the IOR effect in remitted depression and the hippocampus mechanism
      of the IOR effect in depressive episodes, which offer potential biomarkers for
      the clinical treatment of depression.

PMID- 29575564
TI  - Xanthomonas arboricola pv. pruni, causal agent of bacterial spot of stone fruits
      and almond: its genomic and phenotypic characteristics in the X. arboricola
      species context.
AB  - BACKGROUND: Xanthomonas arboricola pv. pruni (Xap) causes bacterial spot of stone
      fruits and almond, an important disease that may reduce the yield and vigour of
      the trees, as well as the marketability of affected fruits. Xap lies within the
      Xanthomonas genus, which has been intensively studied because of its strain
      specialization and host range complexity. Here, we summarize the recent advances
      in our understanding of the complexities of Xap, including studies of the
      molecular features that result after comparative phenotypic and genomic analyses,
      in order to obtain a clearer overview of the bacterial behaviour and infection
      mechanism in the context of the X. arboricola species. TAXONOMIC STATUS:
      Bacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order
      Xanthomonadales; Family Xanthomonadaceae; Genus Xanthomonas; Species X.
      arboricola; Pathovar pruni. HOST RANGE AND SYMPTOMS: Xap infects most Prunus
      species, including apricot, peach, nectarine, plum and almond, and occasionally
      cherry. Symptoms are found on leaves, fruits, twigs and branches or trunks. In
      severe infections, defoliation and fruit dropping may occur. DISTRIBUTION:
      Bacterial spot of stone fruits and almond is worldwide in distribution, with Xap
      being isolated in Africa, North and South America, Asia, Europe and Oceania. It
      is a common disease in geographical areas in which stone fruits and almonds are
      grown. Xap is listed as a quarantine organism in several areas of the world.
      GENOME: The genomes of six isolates from Xap have been publicly released. The
      genome consists of a single chromosome of around 5 000 000 bp with 65 mol% GC
      content and an extrachromosomal plasmid element of around 41 000 bp with 62 mol%
      GC content. Genomic comparative studies in X. arboricola have allowed the
      identification of putative virulence components associated with the infection
      process of bacterial spot of stone fruits and almond. DISEASE CONTROL: Management
      of bacterial spot of stone fruits and almond is based on an integrated approach
      that comprises essential measures to avoid Xap introduction in a production zone,
      as well as the use of tolerant or resistant plant material and chemical
      treatments, mainly based on copper compounds. Management programmes also include
      the use of appropriate cultivation practices when the disease is already
      established. Finally, for the effective control of the disease, appropriate
      detection and characterization methods are needed for use in symptomatic or
      asymptomatic samples as a first approach for pathogen exclusion. USEFUL WEBSITES:
      https://gd.eppo.int/taxon/XANTPR; http://www.cost.eu/COST_Actions/ca/CA16107;
      http://www.xanthomonas.org.

PMID- 29575565
TI  - Beta-peripapillary atrophy of the optic disc and its determinants in Japanese
      eyes: a population-based study.
AB  - PURPOSES: To assess beta-zone of peripapillary atrophy (beta-PPA) and its
      relationship between systemic and ocular factors, especially glaucoma, in a
      Japanese population. METHODS: Fundus photographs obtained from 2129 normal, 84
      primary open-angle glaucoma (POAG) and 10 primary angle closure glaucoma subjects
      from 3021 participants aged 40 years or older in the Tajimi Study were analysed
      planimetrically. If both eyes of a subject met inclusion criteria, one eye was
      randomly chosen. RESULTS: The presence rates of beta-PPA were 54.7 and 77.4% (p <
      0.001) and beta-PPA area averaged 0.67 and 1.06 mm2 (p < 0.001), in normal and
      POAG eyes, respectively. Myopia was closely related to disc ovality and beta-PPA.
      In normal eyes, logistic analysis showed that the presence of beta-PPA was
      correlated with older age, female gender, myopic refraction, thicker central
      corneal thickness (CCT), greater disc ovality and disc centre to fovea (disc
      fovea) distance and lower intraocular pressure (IOP) (p = 0.039 ~ <0.001); and
      multiple regression analysis showed that beta-PPA area was correlated with older
      age, myopic refraction, greater disc area and ovality, disc-fovea distance and
      lower IOP (p = 0.004 ~ <0.001) after adjusting other factors. CONCLUSIONS: The
      presence and size of beta-PPA in normal eyes were correlated with older age,
      greater disc ovality and disc-fovea distance and lower IOP. Further, its presence
      was associated with female gender, thicker CCT and its size with greater disc
      area. beta-zone of peripapillary atrophy (beta-PPA) was also associated with
      POAG. These results provide reference data of the beta-PPA in a Japanese
      population and possibly indicate clinical importance of beta-PPA in glaucoma
      clinic.

PMID- 29575567
TI  - A 16S rRNA gene sequencing and analysis protocol for the Illumina MiniSeq
      platform.
AB  - High-throughput sequencing of the 16S rRNA gene on the Illumina platform is
      commonly used to assess microbial diversity in environmental samples. The
      MiniSeq, Illumina's latest benchtop sequencer, enables more cost-efficient DNA
      sequencing relative to larger Illumina sequencing platforms (e.g., MiSeq). Here
      we used a modified custom primer sequencing approach to test the fidelity of the
      MiniSeq for high-throughput sequencing of the V4 hypervariable region of 16S rRNA
      genes from complex communities in environmental samples. To this end, we designed
      additional sequencing primers that enabled application of a dual-index barcoding
      method on the MiniSeq. A mock community was sequenced alongside the environmental
      samples in four different sequencing runs as a quality control benchmark. We were
      able to recapture a realistic richness of the mock community in all sequencing
      runs, and identify meaningful differences in alpha and beta diversity in the
      environmental samples. Furthermore, rarefaction analysis indicated diversity in
      many environmental samples was close to saturation. These results show that the
      MiniSeq can produce similar quantities of high-quality V4 reads compared to the
      MiSeq, yet is a cost-effective option for any laboratory interested in performing
      high-throughput 16S rRNA gene sequencing.

PMID- 29575566
TI  - Assessing glycation-mediated changes in human cortical bone with Raman
      spectroscopy.
AB  - Establishing a non-destructive method for spatially assessing advanced glycation
      end-products (AGEs) is a potentially useful step toward investigating the
      mechanistic role of AGEs in bone quality. To test the hypothesis that the shape
      of the amide I in the Raman spectroscopy (RS) analysis of bone matrix changes
      upon AGE accumulation, we incubated paired cadaveric cortical bone in ribose or
      glucose solutions and in control solutions for 4 and 16 weeks, respectively, at
      37 degrees C. Acquiring 10 spectra per bone with a 20X objective and a 830 nm
      laser, RS was sensitive to AGE accumulation (confirmed by biochemical
      measurements of pentosidine and fluorescent AGEs). Hyp/Pro ratio increased upon
      glycation using either 0.1 M ribose, 0.5 M ribose or 0.5 M glucose. Glycation
      also decreased the amide I sub-peak ratios (cm-1 ) 1668/1638 and 1668/1610 when
      directly calculated using either second derivative spectrum or local maxima of
      difference spectrum, though the processing method (eg, averaged spectrum vs
      individual spectra) to minimize noise influenced detection of differences for the
      ribose-incubated bones. Glycation however did not affect these sub-peak ratios
      including the matrix maturity ratio (1668/1690) when calculated using indirect
      sub-band fitting. The amide I sub-peak ratios likely reflected changes in the
      collagen I structure.

PMID- 29575568
TI  - Association Between Serotonin Syndrome and Second-Generation Antipsychotics via
      Pharmacological Target-Adverse Event Analysis.
AB  - Case reports suggest an association between second-generation antipsychotics
      (SGAs) and serotonin syndrome (SS). The US Food and Drug Administration (FDA)
      Adverse Event Reporting System (FAERS) was analyzed to generate hypotheses about
      how SGAs may interact with pharmacological targets associated with SS. FAERS was
      integrated with additional sources to link information about adverse events with
      drugs and targets. Using Proportional Reporting Ratios, we identified signals
      that were further investigated with the literature to evaluate mechanistic
      hypotheses formed from the integrated FAERS data. Analysis revealed common
      pharmacological targets perturbed in both SGA and SS cases, indicating that SGAs
      may induce SS. The literature also supported 5-HT2A antagonism and 5-HT1A agonism
      as common mechanisms that may explain the SGA-SS association. Additionally,
      integrated FAERS data mining and case studies suggest that interactions between
      SGAs and other serotonergic agents may increase the risk for SS. Computational
      analysis can provide additional insights into the mechanisms underlying the
      relationship between SGAs and SS.

PMID- 29575570
TI  - Engineering 3D Ru/Graphene Aerogel Using Metal-Organic Frameworks: Capture and
      Highly Efficient Catalytic CO Oxidation at Room Temperature.
AB  - Noble metals (Au, Pt, and Ru) loaded into carbon supports show excellent
      performance for CO oxidation. Herein, a tunable metal-organic framework (MOF)
      coating is applied to a macroscopic 3D Ru/graphene aerogel (Ru/GA) composite,
      using a facial step-by-step method. The open macroporous structure of the Ru/GA
      provides pathways for the access and diffusion of reactant and product molecules.
      The resulting HK (HKUST-1)-containing MOF composite exhibits good performance for
      CO adsorption. It can simultaneously adsorb and oxidize CO, which improves the
      reaction rate. In this work, the catalytic efficiency of the resulting catalyst
      is higher than that (~48.4%) of the Ru/GA. These findings provide a simple method
      for increasing the instantaneous concentration of reactants around the catalyst,
      which in turn increases the reaction rate. The catalytic performances of
      composites subjected to different pretreatment conditions are also investigated.
      Hopefully, this finding may provide a feasible direction for the effective
      management of the diverse environment issues.

PMID- 29575571
TI  - Tissue oximetry by diffusive reflective visible light spectroscopy: Comparison of
      algorithms and their robustness.
AB  - It is essential to measure tissue oxygen saturation (StO2 ) locally and in thin
      layers of tissue, for example, the bronchial mucosa, skin flaps and small bones.
      Visible light spectroscopy (VLS) with a shallow penetration depth is suitable
      method. Although several VLS algorithms have been developed and described, they
      have not yet been compared to each other. This hinders attempts to compare the
      clinical results obtained by different algorithms. To address this issue, we
      compared the algorithms of Harrison, Knoefel, Pittman-Duling, Sato and our OxyVLS
      oximeter, which applies the algorithm from Wodick and Lubbers, in a liquid
      phantom with optical properties of human tissue. We generally observed
      considerable differences between the algorithms, which were StO2 dependent.
      Exceptions were OxyVLS and Sato, showing a high level of agreement with
      negligible StO2 dependency. In spite of the considerable deviation between the
      other algorithms, the difference of StO2 between them in clinically normal StO2
      was <10%. We did not observe any dependency of the algorithms on hemoglobin
      content of the phantom or temperature.

PMID- 29575569
TI  - Clinical, biochemical, and genetic features of four patients with short-chain
      enoyl-CoA hydratase (ECHS1) deficiency.
AB  - Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error
      of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292).
      Clinical presentation includes infantile-onset severe developmental delay,
      regression, seizures, elevated lactate, and brain MRI abnormalities consistent
      with Leigh syndrome (LS). Characteristic abnormal biochemical findings are
      secondary to dysfunction of valine metabolism. We describe four patients from two
      consanguineous families (one Pakistani and one Irish Traveler), who presented in
      infancy with LS. Urine organic acid analysis by GC/MS showed increased levels of
      erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconate (3-MGC). Increased
      urine excretion of methacrylyl-CoA and acryloyl-CoA related metabolites analyzed
      by LC-MS/MS, were suggestive of SCEH deficiency; this was confirmed in patient
      fibroblasts. Both families were shown to harbor homozygous pathogenic variants in
      the ECHS1 gene; a c.476A > G (p.Gln159Arg) ECHS1variant in the Pakistani family
      and a c.538A > G, p.(Thr180Ala) ECHS1 variant in the Irish Traveler family. The
      c.538A > G, p.(Thr180Ala) ECHS1 variant was postulated to represent a Canadian
      founder mutation, but we present SNP genotyping data to support Irish ancestry of
      this variant with a haplotype common to the previously reported Canadian patients
      and our Irish Traveler family. The presence of detectable erythro-2,3-dihydroxy-2
      methylbutyrate is a nonspecific marker on urine organic acid analysis but this
      finding, together with increased excretion of 3-MGC, elevated plasma lactate, and
      normal acylcarnitine profile in patients with a Leigh-like presentation should
      prompt consideration of a diagnosis of SCEH deficiency and genetic analysis of
      ECHS1. ECHS1 deficiency can be added to the list of conditions with 3-MGA.

PMID- 29575572
TI  - Functional expansion pharyngoplasty: Technical update by unidirectional barbed
      sutures.

PMID- 29575573
TI  - Renal sympathetic denervation: Ashes to ashes or rebirth from the ashes?

PMID- 29575575
TI  - Endostar (rh-endostatin) versus placebo in combination with vinorelbine plus
      cisplatin chemotherapy regimen in treatment of advanced non-small cell lung
      cancer: A meta-analysis.
AB  - BACKGROUND: This meta-analysis was conducted to investigate the efficacy and
      safety of Endostar (rh-endostatin) versus a placebo in combination with a
      vinorelbine plus cisplatin (NP) chemotherapy regimen for the treatment of
      advanced non-small cell lung cancer (NSCLC). METHODS: Two reviewers independently
      searched Medline, PubMed, the Cochrane Central Register of Controlled Trials
      (CENTRAL), Embase, ASCO, ESMO, the Web of Science, and CNKI databases to locate
      relevant controlled clinical trials. The treatment efficacy and drug-related
      toxicity of NP + Endostar (NPE) and NP groups were pooled through meta-analysis
      according to random or fixed effect models. RESULTS: Fifteen prospective clinical
      studies were included in this meta-analysis. The pooled risk ratio (RR) for
      objective response rate was 1.74 (95% confidence interval [CI] 1.43-2.11); the
      objective response rate in the NPE group was significantly higher than in the NP
      group (P < 0.05). Nine publications evaluated the incidence of leucopenia between
      Endostar versus a placebo in combination with an NP chemotherapy regimen. The
      pooled results showed no statistically significant difference between NPE and NP
      chemotherapy regimens for leucopenia, thrombocytopenia, and nausea/vomiting risk
      (P > 0.05). The one-year survival rate in the NPE group was higher than in the NP
      group, with a statistically significant difference (RR = 1.70, 95% CI 1.07-2.89;
      P < 0.05). CONCLUSION: Endostar combined with an NP chemotherapy regimen can
      improve the prognosis of patients with advanced NSCLC without increasing the risk
      of toxicity.

PMID- 29575576
TI  - The mitochondrial unfolded protein response is activated upon hematopoietic stem
      cell exit from quiescence.
AB  - The mitochondrial unfolded protein response (UPRmt ), a cellular protective
      program that ensures proteostasis in the mitochondria, has recently emerged as a
      regulatory mechanism for adult stem cell maintenance that is conserved across
      tissues. Despite the emerging genetic evidence implicating the UPRmt in stem cell
      maintenance, the underlying molecular mechanism is unknown. While it has been
      speculated that the UPRmt is activated upon stem cell transition from quiescence
      to proliferation, the direct evidence is lacking. In this study, we devised three
      experimental approaches that enable us to monitor quiescent and proliferating
      hematopoietic stem cells (HSCs) and provided the direct evidence that the UPRmt
      is activated upon HSC transition from quiescence to proliferation, and more
      broadly, mitochondrial integrity is actively monitored at the restriction point
      to ensure metabolic fitness before stem cells are committed to proliferation.

PMID- 29575578
TI  - Direct-Patterning SWCNTs Using Dip Pen Nanolithography for SWCNT/Silicon Solar
      Cells.
AB  - Dip pen nanolithography (DPN) is used to pattern single-walled carbon nanotube
      (SWCNT) lines between the n-type Si and SWCNT film in SWCNT/Si solar cells. The
      SWCNT ink composition, loading, and DPN pretreatment are optimized to improve
      patterning. This improved DPN technique is then used to successfully pattern >1
      mm long SWCNT lines consistently. This is a 20-fold increase in the previously
      reported direct-patterning of SWCNT lines using the DPN technique, and
      demonstrates the scalability of the technique to pattern larger areas. The degree
      of the uniformity of SWCNTs in these lines is further characterized by Raman
      spectroscopy and scanning electron microscopy. The patterned SWCNT lines are used
      as thin conductive pathways in SWCNT/Si solar cells, similar to front contact
      electrodes. The critical parameters of these solar cells are measured and
      compared to control cells without SWCNT lines. The addition of SWCNT lines
      increases power conversion efficiency by 40% (relative). Importantly, the SWCNT
      lines reduce average series resistance by 44%, and consequently increase average
      fill factor by 24%.

PMID- 29575577
TI  - Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by
      multilayer compensatory mechanisms.
AB  - To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly
      controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in
      hepcidin regulation remains elusive. We generated and characterized hepatocyte
      specific Smad7 knockout mice (Smad7Alb/Alb ), which showed decreased serum iron,
      tissue iron, haemoglobin concentration, up-regulated hepcidin and increased
      phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues.
      Increased levels of hepcidin lead to reduced expression of intestinal ferroportin
      and mild iron deficiency anaemia. Interestingly, we found no difference in
      hepcidin expression or phosphor-Smad1/5/8 levels between iron-challenged
      Smad7Alb/Alb and Smad7flox/flox , suggesting other factors assume the role of
      iron-induced hepcidin regulation in Smad7 deletion. We performed RNA-seq to
      identify differentially expressed genes in the liver. Significantly up-regulated
      genes were then mapped to pathways, revealing TGF-beta signalling as one of the
      most relevant pathways, including the up-regulated genes Smad6, Bambi and Fst
      (Follistatin). We found that Smad6 and Bambi-but not Follistatin-are controlled
      by the iron-BMP-Smad pathway. Overexpressing Smad6, Bambi or Follistatin in cells
      significantly reduced hepcidin expression. Smad7 functions as a key regulator of
      iron homoeostasis by negatively controlling hepcidin expression, and Smad6 and
      Smad7 have non-redundant roles. Smad6, Bambi and Follistatin serve as additional
      inhibitors of hepcidin in the liver.

PMID- 29575579
TI  - Continuing Professional Development.

PMID- 29575580
TI  - Editorial Profiles.

PMID- 29575581
TI  - Is this keratoconus?

PMID- 29575582
TI  - Imaging the deep optic nerve: developing mechanistic biomarkers for glaucoma.

PMID- 29575583
TI  - Global effects of plant litter alterations on soil CO2 to the atmosphere.
AB  - Soil respiration (Rs) is the largest terrestrial carbon (C) efflux to the
      atmosphere and is predicted to increase drastically through global warming.
      However, the responses of Rs to global warming are complicated by the fact that
      terrestrial plant growth and the subsequent input of plant litter to soil are
      also altered by ongoing climate change and human activities. Despite a number of
      experiments established in various ecosystems around the world, it remains a
      challenge to predict the magnitude and direction of changes in Rs and its
      temperature sensitivity (Q10 ) due to litter alteration. We present a meta
      analysis of 100 published studies to examine the responses of Rs and Q10 to
      manipulated aboveground and belowground litter alterations. We found that 100%
      aboveground litter addition (double litter) increased Rs by 26.1% (95% confident
      intervals, 18.4%-33.7%), whereas 100% aboveground litter removal, root removal
      and litter + root removal reduced Rs by 22.8% (18.5%-27.1%), 34.1% (27.2%-40.9%)
      and 43.4% (36.6%-50.2%) respectively. Moreover, the effects of aboveground double
      litter and litter removal on Rs increased with experimental duration, but not
      those of root removal. Aboveground litter removal marginally increased Q10 by
      6.2% (0.2%-12.3%) because of the higher temperature sensitivity of stable C
      substrate than fresh litter. Estimated from the studies that simultaneously
      tested the responses of Rs to aboveground litter addition and removal and
      assuming negligible changes in root-derived Rs, "priming effect" on average
      accounted for 7.3% (0.6%-14.0%) of Rs and increased over time. Across the global
      variation in terrestrial ecosystems, the effects of aboveground litter removal,
      root removal, litter + root removal on Rs as well as the positive effect of
      litter removal on Q10 increased with water availability. Our meta-analysis
      indicates that priming effects should be considered in predicting Rs to climate
      change-induced increases in litterfall. Our analysis also highlights the need to
      incorporate spatial climate gradient in projecting long-term Rs responses to
      litter alterations.

PMID- 29575584
TI  - The effect of implant-abutment junction position on crestal bone loss: A
      systematic review and meta-analysis.
AB  - PURPOSE: To investigate the effect of the apico-coronal implant position on early
      and late crestal bone loss (CBL), in bone and tissue level implants. MATERIALS
      AND METHODS: Electronic and manual literature searches were conducted for
      controlled clinical trials reporting on CBL before and after functional loading
      of implants. Random effects meta-analyses were applied to analyze the weighted
      mean difference (WMD) and meta-regression was conducted to investigate any
      potential influences of select confounding factors. RESULTS: Fourteen articles
      were included in the systematic review and 12 were included in the quantitative
      synthesis. For bone level implants, WMD comparing early CBL in equi and
      subcrestal placement was 0.15 mm (P = .18). For analyses of late CBL in bone
      level implants, equi and subcrestal placement revealed a 0.03 mm WMD (P = .88).
      Where in supra and subcrestal placement, WMD was 0.04 mm (P = .86). The
      comparison presented considerable heterogeneity between these two arms, where the
      P value for chi-square test presented as .006. Finally, for CBL between supra and
      equicrestal placement, WMD was -0.64 mm (P < .0001), favoring the supracrestal
      group. For tissue level implants, WM of early and late CBL in implants placed
      equi-crestally was 0.68 +/- 0.12 mm and 0.69 +/- 0.54 mm, respectively, where for
      implants placed sub-crestally, the WM of CBL was 1.72 +/- 0.15 mm and 2.26 +/-
      0.63 mm, respectively. CONCLUSION: Within the limitations of this study, it is
      recommended to place tissue level implants equicrestally, and bone level implants
      subcrestally.

PMID- 29575585
TI  - Clinical genetic counselors: An asset in the era of precision medicine.
AB  - Trying to predict what genetic counseling will look like in the era of precision
      medicine is a continuous challenge. According to the National Institutes of
      Health, precision medicine is an emerging approach for disease treatment and
      prevention that takes into account individual variability in genes, environment,
      and lifestyle. In order to explore the future of genetic counseling practice in
      this era, this article examines the current genetic counseling practice, internal
      and external forces that most likely will continue to shape the genetic
      counseling profession, and discusses the most important aspects of what genetic
      counselors have to offer in the era of precision medicine.

PMID- 29575586
TI  - Correlation between observation task performance and visual acuity, contrast
      sensitivity and environmental light in a simulated maritime study.
AB  - PURPOSE: To examine the relevance of visual acuity (VA) and index of contrast
      sensitivity (ICS) as predictors for visual observation task performance in a
      maritime environment. METHODS: Sixty naval cadets were recruited to a study on
      observation tasks in a simulated maritime environment under three different light
      settings. Their ICS were computed based on contrast sensitivity (CS) data
      recorded by Optec 6500 and CSV-1000E CS tests. The correlation between object
      identification distance and VA/ICS was examined by stepwise linear regression.
      RESULTS: The object detection distance was significantly correlated to the level
      of environmental light (p < 0.001), but not to the VA or ICS recorded in the test
      subjects. Female cadets had a significantly shorter target identification range
      than the male cadets. CONCLUSION: Neither CS nor VA were found to be
      significantly correlated to observation task performance. This apparent absence
      of proven predictive value of visual parameters for observation tasks in a
      maritime environment may presumably be ascribed to the normal and uniform visual
      capacity in all our study subjects.

PMID- 29575588
TI  - Exercise on-transition uncoupling of ventilatory, gas exchange and cardiac
      hemodynamic kinetics accompany pulmonary oxygen stores depletion to impact
      exercise intolerance in human heart failure.
AB  - AIM: In contrast to knowledge that heart failure (HF) patients demonstrate peak
      exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics,
      whether this dyssynchrony follows that at the exercise on-transition is unclear.
      This study tested whether exercise on-transition temporal lag for ventilation
      relative to gas exchange and oxygen pulse (O2 pulse) couples with effects from
      abnormal pulmonary gaseous oxygen store (O2store ) contributions to VO2 to
      interdependently precipitate persistently elevated ventilatory demand and low
      oxidative metabolic capacity in HF. METHODS: Beat-to-beat HR and breath-to-breath
      ventilation and gas exchange were continuously acquired in HF (N = 9, ejection
      fraction = 30 +/- 9%) and matched controls (N = 10) during square-wave ergometry
      at 60% VO2peak (46 +/- 14 vs 125 +/- 54-W, P < .001). Temporal responses across
      VE , VO2 and O2 pulse were assessed for the exercise on-transition using single
      exponential model Phase II on-kinetic time constants (tau = time to reach 63%
      steady-state rise). Breath-to-breath gas fractions and respiratory flows were
      used to determine O2stores . RESULTS: HF vs controls: tau for VE (137 +/- 93 vs
      74 +/- 40-seconds, P = .03), VO2 (60 +/- 40 vs 23 +/- 5-seconds, P = .03) and O2
      pulse (28 +/- 18 vs 23 +/- 15-seconds, P = .59). Within HF, tau for VE differed
      from O2 pulse (P < .02), but not VO2 . Exercise VE rise (workload indexed)
      differed in HF vs controls (545 +/- 139 vs 309 +/- 88-mL min-1 W-1 , P < .001).
      Exercise on-transition O2store depletion in HF exceeded controls, generally
      persisting to end-exercise. CONCLUSION: These data suggest HF demonstrated
      exercise on-transition O2store depletion (high O2store contribution to VO2 )
      coupled with dyssynchronous VE , VO2 and O2 pulse kinetics-not attributable to
      prolonged cardiac haemodynamics. Persistent high ventilatory demand and low
      oxidative metabolic capacity in HF may be precipitated by physiological
      uncoupling occurring within the exercise on-transition.

PMID- 29575587
TI  - Outcomes of Patients With Syncope and Suspected Dementia.
AB  - OBJECTIVES: Syncope and near-syncope are common in patients with dementia and a
      leading cause of emergency department (ED) evaluation and subsequent
      hospitalization. The objective of this study was to describe the clinical
      trajectory and short-term outcomes of patients who presented to the ED with
      syncope or near-syncope and were assessed by their ED provider to have dementia.
      METHODS: This multisite prospective cohort study included patients 60 years of
      age or older who presented to the ED with syncope or near-syncope between 2013
      and 2016. We analyzed a subcohort of 279 patients who were identified by the
      treating ED provider to have baseline dementia. We collected comprehensive
      patient-level, utilization, and outcomes data through interviews, provider
      surveys, and chart abstraction. Outcome measures included serious conditions
      related to syncope and death. RESULTS: Overall, 221 patients (79%) were
      hospitalized with a median length of stay of 2.1 days. A total of 46 patients
      (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized
      patients who did not have a serious condition identified in the ED, 14 (7.8%)
      were subsequently diagnosed with a serious condition during the hospitalization,
      and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days
      of the index ED visit. There were seven deaths (2.5%) overall, none of which were
      cardiac-related. No patients who were discharged from the ED died or had a
      serious condition in the subsequent 30 days. CONCLUSIONS: Patients with perceived
      dementia who presented to the ED with syncope or near-syncope were frequently
      hospitalized. The diagnosis of a serious condition was uncommon if not identified
      during the initial ED assessment. Given the known iatrogenic risks of
      hospitalization for patients with dementia, future investigation of the impact of
      goals of care discussions on reducing potentially preventable, futile, or
      unwanted hospitalizations while improving goal-concordant care is warranted.

PMID- 29575589
TI  - Clinical and esthetic outcome with immediate insertion and provisionalization
      with or without connective tissue grafting in presence of mucogingival
      recessions: A retrospective analysis with follow-up between 1 and 8 years.
AB  - BACKGROUND: Recessions following immediate implant insertion are frequently
      reported in the literature. Data regarding implant installation in presence of
      mucogingival recessions are rare. PURPOSE: This study observes soft tissue level
      changes following immediate implant insertion and provisionalization of implants
      with or without connective tissue grafts in the anterior maxilla in patients with
      initial mucogingival recession within a follow-up period between one and eight
      years. MATERIALS AND METHODS: Twenty-six patients with marginal gingival
      recessions, which were designated for extraction and immediate implant insertion
      in the anterior zone of the maxilla (13-23), were included. Out of a larger group
      of immediate implants only single tooth replacements with 1 to 3 mm recession and
      a pre- and post-op CB-CT were selected. Facial bone deficiencies were grafted
      flaplessly with autologous bone in all sites. In a group of 13 patients the
      recessions (mean 2.3 +/- 0.7 mm, range 1.0-3.0 mm) were grafted additionally by
      connective tissue (ABG + CTG), in the remaining 13 patients no soft tissue
      grafting (mean recession 1.8 +/- 0.6 mm, range 1.0-3.0 mm) was performed (ABG).
      The marginal hard and soft tissue level, the width of the keratinized mucosa, the
      PES, and implant success were evaluated. RESULTS: After a mean follow-up period
      of 45 months the recessions were significantly reduced in the ABG group from 1.8
      to 0.9 mm. The improvement was even more pronounced in the ABG + CTG group (from
      2.3 to 0.5 mm). The PES improved significantly in both groups. At final
      examination all implants were still in function. Within the observational period,
      in 5 of 13 implants a marginal bone loss of more than 1 mm was noticed in the
      ABG, but in none of the ABG + CTG group. CONCLUSIONS: These clinical results
      provide evidence that immediate implant placement might improve the facial soft
      tissue level. This was more evident in cases with a greater recession and an
      additional treatment with connective tissue grafts.

PMID- 29575591
TI  - Improved clonality detection in Hodgkin lymphoma using a semi-nested modification
      of the BIOMED-2 PCR assay for IGH and IGK rearrangements: A paraffin-embedded
      tissue study.
AB  - The BIOMED-2 PCR protocols targeting IGH and IGK genes may be useful for
      detecting clonality in Hodgkin lymphoma (HL). The clonality detection rates,
      however, have not been very high with these methods using paraffin-embedded tumor
      sections. We previously described the usefulness of the semi-nested BIOMED-2 IGH
      assay in B-cell malignancies. In this study, we devised a novel semi-nested
      BIOMED-2 IGK assay. Employing 58 cases of classical HL, we carried out the
      standard BIOMED-2, BIOMED-2 followed by BIOMED-2 re-amplification, and BIOMED-2
      followed by semi-nested BIOMED-2, all targeting IGH and IGK, using paraffin
      embedded tissues. In both IGH and IGK assays, semi-nested assays yielded
      significantly higher clonality detection rates than the standard assays and re
      amplification assays. Clonality was detected in 13/58 (22.4%) classical HL cases
      using the standard IGH/IGK assays while it was detected in 38/58 (65.5%) cases
      using semi-nested IGH/IGK assays. The detection rates were not associated with
      the HL subtypes, CD30-positive cell density, CD20-positive cell density, or
      Epstein-Barr virus (EBV) positivity. In conclusion, tumor clonality was detected
      in nearly two-thirds of classical HL cases using semi-nested BIOMED-2 IGH/IGK
      assays using paraffin tumor sections. These semi-nested assays may be useful when
      the standard IGH/IGK assays fail to detect clonality in histopathologically
      suspected HLs.

PMID- 29575590
TI  - Resistance to discontinuing breast cancer screening in older women: A qualitative
      study.
AB  - OBJECTIVE: Screening mammography is associated with reduced breast cancer
      specific mortality; however, among older women, evidence suggests that the
      potential harms of screening may outweigh the benefits. We used a qualitative
      approach to examine the willingness of older women from different racial/ethnic
      groups to discontinue breast cancer screening. METHODS: Women >=70 years of age
      who reported having a screening mammogram in the past 3 years and/or reported
      that they intended to continue screening in the future were recruited for in
      depth interviews. Participants who intended to continue screening were asked to
      describe how the following hypothetical scenarios would impact a decision to
      discontinue screening: health concerns or limited life expectancy, a physician's
      recommendation to discontinue, reluctance to undergo treatment, and
      recommendations from experts or governmental panels to stop screening. Semi
      structured, face-to-face interviews were audio-recorded. Data coding and analysis
      followed inductive and deductive approaches. RESULTS: Regardless of the scenario,
      participants (n = 29) expressed a strong intention to continue screening. Based
      on the hypothetical physician recommendations, intentions to continue screening
      appeared to remain strong. They did not envision a change in their health status
      that would lead them to discontinue screening and were skeptical of
      expert/government recommendations. There were no differences observed according
      to age, race/ethnicity, or education. CONCLUSIONS: Among older women who planned
      to continue screening, intentions to continue breast cancer screening appear to
      be highly resilient and resistant to recommendations from physicians or
      expert/government panels.

PMID- 29575592
TI  - Connectivity of the ventral visual cortex is necessary for object recognition in
      patients.
AB  - The functional profiles of regions in the ventral occipital-temporal cortex
      (VTC), a critical region for object visual recognition, are associated with the
      VTC connectivity patterns to nonvisual regions relevant to the corresponding
      object domain. However, whether and how whole-brain connections affect
      recognition behavior remains untested. We directly examined the necessity of VTC
      connectivity in object recognition behavior by testing 82 patients whose lesion
      spared relevant VTC regions but affected various white matter (WM) tracts and
      other regions. In these patients, we extracted the whole-brain anatomical
      connections of two VTC domain-selective (large manmade objects and animals)
      clusters with probabilistic tractography, and examined whether such connectivity
      pattern can predict recognition performance of the corresponding domains with
      support vector regression (SVR) analysis. We found that the whole-brain
      anatomical connectivity of large manmade object-specific cluster successfully
      predicted patients' large object recognition performance but not animal
      recognition or control tasks, even after we excluded connections with early
      visual regions. The contributing connections to large object recognition included
      tracts between VTC-large object cluster and distributed regions both within and
      beyond the visual cortex (e.g., putamen, superior, and middle temporal gyrus).
      These results provide causal evidence that the VTC whole-brain anatomical
      connectivity is necessary for at least certain domains of object recognition
      behavior.

PMID- 29575593
TI  - Utility of autopsy brain imprint and squash cytology for detection of
      lymphoma/leukemia emboli in select patients presenting with rapid decline in
      mental status.
AB  - Central nervous system (CNS) hematologic malignancies, whether primary or
      secondary, are uncommon and their clinical presentations vary. Intravascular
      lymphoma (IVL) is a very rare, aggressive systemic malignancy that is often
      difficult to diagnose and susceptible to early CNS involvement. Blast crisis in
      myeloid leukemias can cause widespread neoplastic emboli. Here, we report two
      adult patients (72 years and 22 years of age) who presented with altered mental
      status followed by rapid decline in their conditions leading to death. No prior
      significant medical history was present for either patient, while acute myeloid
      leukemia was diagnosed in the younger patient immediately before death. During
      autopsy, we performed imprint and squash preparations, and frozen sections of
      representative cerebral cortex, cerebellum, leptomeninges, and the pituitary
      gland. In the older patient, presence of IVL was readily detected on cytologic
      preparations. Diffuse involvement of brain vasculature and perivascular
      parenchyma with acute myeloid leukemia was identified in the other patient.
      Although examination of the fresh brain is not routinely performed during
      autopsy, these cases are presented to illustrate that imprint and squash
      preparations can provide a rapid and reliable provisional autopsy diagnosis in
      select patients.

PMID- 29575594
TI  - Preoperative weight loss program involving a 20-day very low-calorie diet for
      obesity before laparoscopic gastrectomy for gastric cancer.
AB  - INTRODUCTION: The increased visceral fat in patients with obesity can increase
      the technical difficulty of surgery. This study was performed to evaluate a
      preoperative 20-day very low-calorie diet for obesity before laparoscopic
      gastrectomy for gastric cancer. METHODS: This prospective single-center study
      involved patients with obesity who were planning to undergo laparoscopic
      gastrectomy for gastric cancer. Obesity was defined according to the Japanese
      criteria: BMI >=25 kg/m2 or waist circumference >=85 cm in men and >=90 cm in
      women. The patients underwent a preoperative 20-day very low-calorie diet and
      received nutritional counseling. Weight loss, body composition, visceral fat
      mass, and operative outcomes were evaluated. RESULTS: Thirty-three patients were
      enrolled from September 2013 to August 2015. Their median age was 71 years, and
      78.8% were men. Their median bodyweight and BMI were 72.3 kg (range, 53.8-82.5
      kg) and 26.0 kg/m2 (range, 23.5-31.0 kg/m2 ), respectively. The patients achieved
      a mean weight loss of 4.5% (95% confidence interval [CI]: 3.8-5.1), corresponding
      to 3.2 kg (95%CI: 2.7-3.7 kg). Body fat mass was significantly decreased by a
      mean of 2.5 kg (95%CI: 1.9-3.1), whereas skeletal muscle mass was unaffected
      (mean: -0.20 kg [95%CI: -0.55-0.15]). The visceral fat mass reduction rate was
      high as 16.8% (range, 11.6%-22.0%). All patients underwent laparoscopic
      gastrectomy as planned. Severe postoperative morbidity (Clavien-Dindo grade
      >=III) was seen in only one patient (3.0%). CONCLUSION: The preoperative 20-day
      very low-calorie diet weight loss program is promising for the treatment of
      obesity before laparoscopic gastrectomy for gastric cancer.

PMID- 29575595
TI  - Ultraviolet Photoluminescence of Carbon Nanospheres and its Surface Plasmon
      Induced Enhancement.
AB  - Ultraviolet (UV) light can be used in versatile applications ranging from
      photoelectronic devices to biomedical imaging. In the development of new UV light
      sources, in this study, stable UV emission at ~350 nm is unprecedentedly obtained
      from carbon nanospheres (CNSs). The origin of the UV fluorescence is
      comprehensively investigated via various characterization methods, including
      Raman and Fourier transform infrared analyses, with comparison to the visible
      emission of carbon nanodots. Based on the density functional calculations, the UV
      fluorescence is assigned to the carbon nanostructures bonded to bridging O atoms
      and dangling -OH groups. Moreover, a twofold enhancement in the UV emission is
      acquired for Au-carbon core-shell nanospheres (Au-CNSs). This remarkable
      modification of the UV emission is primarily ascribed to charge transfer between
      the CNSs and the Au surface.

PMID- 29575574
TI  - No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis
      for chronic, inflammatory diseases.
AB  - Since the successful conquest of many acute, communicable (infectious) diseases
      through the use of vaccines and antibiotics, the currently most prevalent
      diseases are chronic and progressive in nature, and are all accompanied by
      inflammation. These diseases include neurodegenerative (e.g. Alzheimer's,
      Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and
      autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may
      appear to have little in common. In fact they all share significant features, in
      particular chronic inflammation and its attendant inflammatory cytokines. Such
      effects do not happen without underlying and initially 'external' causes, and it
      is of interest to seek these causes. Taking a systems approach, we argue that
      these causes include (i) stress-induced iron dysregulation, and (ii) its ability
      to awaken dormant, non-replicating microbes with which the host has become
      infected. Other external causes may be dietary. Such microbes are capable of
      shedding small, but functionally significant amounts of highly inflammagenic
      molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include
      significant coagulopathies, not least the recently discovered amyloidogenic
      clotting of blood, leading to cell death and the release of further inflammagens.
      The extensive evidence discussed here implies, as was found with ulcers, that
      almost all chronic, infectious diseases do in fact harbour a microbial component.
      What differs is simply the microbes and the anatomical location from and at which
      they exert damage. This analysis offers novel avenues for diagnosis and
      treatment.

PMID- 29575596
TI  - Verification of Acuros XB dose algorithm using 3D printed low-density phantoms
      for clinical photon beams.
AB  - The transport-based dose calculation algorithm Acuros XB (AXB) has been shown to
      accurately account for heterogeneities primarily through comparisons with Monte
      Carlo simulations. This study aims to provide additional experimental
      verification of AXB for clinically relevant flattened and unflattened beam
      energies in low density phantoms of the same material. Polystyrene slabs were
      created using a bench-top 3D printer. Six slabs were printed at varying densities
      from 0.23 to 0.68 g/cm3 , corresponding to different density humanoid tissues.
      The slabs were used to form different single and multilayer geometries. Dose was
      calculated with EclipseTM AXB 11.0.31 for 6MV, 15MV flattened and 6FFF
      (flattening filter free) energies for field sizes of 2 * 2 and 5 * 5 cm2 . EBT3
      film was inserted into the phantoms, which were irradiated. Absolute dose
      profiles and 2D Gamma analyses were performed for 96 dose planes. For all single
      slab configurations and energies, absolute dose differences between the AXB
      calculation and film measurements remained <3% for both fields in the high-dose
      region, however, larger disagreement was seen within the penumbra. For the
      multilayered phantom, percentage depth dose with AXB was within 5% of discrete
      film measurements. The Gamma index at 2%/2 mm averaged 98% in all combinations of
      fields, phantoms and photon energies. The transport-based dose algorithm AXB is
      in good agreement with the experimental measurements for small field sizes using
      6MV, 6FFF and 15MV beams adjacent to various low-density heterogeneous media.
      This work provides preliminary experimental grounds to support the use of AXB for
      heterogeneous dose calculation purposes.

PMID- 29575598
TI  - Effects of polyphenolic extract from Eucommia ulmoides Oliver leaf on growth
      performance, digestibility, rumen fermentation and antioxidant status of
      fattening lambs.
AB  - To investigate the effects of polyphenolic extract from Eucommia ulmoides Oliver
      leaf (PEEU) on growth performance, digestibility, rumen fermentation and
      antioxidant status of fattening lambs, 30 weaned male Huzhou lambs were equally
      divided into three treatments and fed the basal diet supplemented with 0 (CON), 5
      (PEEU5) or 10 (PEEU10) g/kg PEEU. Dietary PEEU supplementation did not affect
      growth performance and apparent digestibility of nutrients. Compared with the CON
      group, lambs in the PEEU10 group had lower ammonia nitrogen concentration (p <
      .01) and acetic acid to propionic acid ratio (p < .05) and higher the molar
      proportion of propionate (p < .05) in rumen fluid. Ammonia nitrogen concentration
      (p < .01) and the molar proportion of propionate (p < .05) were affected by an
      interaction between PEEU and sampling day. Dietary PEEU supplementation at 10
      g/kg increased total antioxidant capacity (p < .05), superoxide dismutase (p <
      .05) and glutathione peroxidase (p < .01) activities in serum and glutathione
      peroxidase activity (p < .05) in liver and decreased (p < .05) malondialdehyde
      content in serum and liver compared with the CON group. In conclusion, dietary
      PEEU supplementation affected rumen fermentation patterns and improved
      antioxidant status of fattening lambs.

PMID- 29575597
TI  - Anti-HLA alloantibodies of the IgA isotype in re-transplant candidates part II:
      Correlation with graft survival.
AB  - We reported previously on the widespread occurrence of anti-HLA alloantibodies of
      the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re
      tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx
      patients, we now extended our earlier findings by examining the impact of the
      presence and donor specificity of anti-HLA IgA on graft survival. We observed
      frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter
      collective of 694 kidney re-tx patients. This subgroup displayed significantly
      reduced graft survival as evidenced by the median time to first dialysis after
      transplantation (TTD 77 months) compared to patients carrying either anti-HLA IgG
      or IgA (TTD 102 and 94 months, respectively). In addition, donor specificity of
      anti-HLA IgA had a significant negative impact on graft survival (TTD 74 months)
      in our study. Taken together, our data strongly indicate that presence of anti
      HLA IgA, in particular in conjunction with anti-HLA-IgG, in sera of kidney re-tx
      patients is associated with negative transplantation outcome.

PMID- 29575599
TI  - Comparability of subjective and objective measurements of nuclear density in
      cataract patients.
AB  - PURPOSE: To evaluate the relationship between subjective and objective
      measurements of lens density and the energy of phacoemulsification. SETTING:
      University Eye Clinic, Maastricht University Medical Centre, Maastricht, the
      Netherlands. DESIGN: Cross-sectional study. METHODS: The study population
      included 69 patients. Nuclear opalescence (NO) was graded with the Lens Opacities
      Classification System III (LOCS III). Thereafter, lens density was measured
      objectively with Scheimpflug imaging, anterior segment optical coherent
      tomography and spectral fundus reflectometry (SFR). Cumulative dissipative energy
      (CDE) and total ultrasound time (US t.t.) of the phacoemulsification were noted.
      The relationship between the different measurement techniques and energy of
      phacoemulsification was assessed using Spearman's correlation coefficients.
      RESULTS: We found moderate to strong correlations between LOCS III and objective
      measurements of the lens density (rho's from 0.53 to 0.78, p < 0.05) and a
      moderate correlation between three objective measurement techniques (rho's
      between 0.29 and 0.57, p < 0.05). There was a moderate correlation between CDE,
      US t.t. and lens density measurements (rho's from 0.29 to 0.55, p < 0.05), and
      the highest correlation was found between CDE and NO scores. Exclusion of
      patients with advanced cortical and posterior subcapsular opacities improved the
      correlation between SFR and lens density measurements but not the correlation
      with the energy of phacoemulsification. CONCLUSION: Lens Opacities Classification
      System III has shown the highest correlation with phacoemulsification energy and
      may be a preferred technique for prediction of use of phacoemulsification energy.
      Advanced cortical and posterior opacities may interfere with the quality of
      objective measurements but do not affect the correlation between lens density
      measurements and phacoemulsification energy.

PMID- 29575600
TI  - Genetic counseling globally: Where are we now?
AB  - The genetic counseling profession is continuing to develop globally, with
      countries in various stages of development. In some, the profession has been in
      existence for decades and is increasingly recognized as an important provider of
      allied health, while in others it is just beginning. In this article, we describe
      the current global landscape of the genetic counseling specialty field's
      professional development. Using examples of the United States, United Kingdom,
      Canada, Australia, South Africa, and various countries in Asia, we highlight the
      following: (a) status of genetic counseling training programs, (b) availability
      of credentialing through government and professional bodies (certification,
      registration, and licensure), and potential for international reciprocity, (c)
      scope of clinical practice, and (d) health-care system disparities and cultural
      differences impacting on practice. The successful global implementation of
      precision medicine will require both an increased awareness of the importance of
      the profession of "genetic counselor" and flexibility in how genetic counselors
      are incorporated into each country's health-care market. In turn, this will
      require more collaboration within and across nations, along with continuing
      engagement of existing genetic counseling professional societies.

PMID- 29575601
TI  - Three-dimensional augmented reality surgical navigation with hybrid optical and
      electromagnetic tracking for distal intramedullary nail interlocking.
AB  - BACKGROUND: Intramedullary nail (IMN) fixation improves functional outcomes for
      the diaphyseal fractures of long bones. However, locking the distal holes of the
      IMN is challenging. Although several navigation methods have been proposed, an
      intuitive, radiation-free and accurate navigation method that does not suffer
      from problems of hand-eye coordination has not yet been described. METHODS: This
      paper proposes an augmented reality (AR) surgical navigation method with hybrid
      optical and electromagnetic (EM) tracking for distal IMN interlocking. Model
      experiments are designed to evaluate the AR-guided distal interlocking method.
      RESULTS: AR-guided drilling procedures were performed on 5 tibia models and a leg
      phantom. The accuracy (hit or miss) was evaluated using fluoroscopy. The
      experimental results demonstrated that all 18 drills successfully hit the distal
      holes at a rate of 100%. CONCLUSIONS: Our results indicate that the AR-guided
      distal interlocking method is feasible and has many potential applications in
      clinic after further evaluation.

PMID- 29575602
TI  - Exosomal tetraspanins as regulators of cancer progression and metastasis and
      novel diagnostic markers.
AB  - Exosomes are cell-cell communicators emerging as a new paradigm for noninvasive
      diagnosis and prognosis of treatment response. Exosomal tetraspanin proteins like
      CD63, CD9 and CD81 play a critical role in sorting, selective recruitment of
      biomolecules, target selection, cell-specific entry, capturing, angiogenesis and
      vasculogenesis. These tetraspanins are being used as markers for oral, colorectal
      and colon cancers and glioblastoma. However, exosomal markers with robust
      specificity for early detection of carcinomas are the furthest along. EXO CARTA
      database shows the presence of CD151 in exosomes of colorectal, melanoma, ovarian
      and prostate cancers. CD151 preferentially targets exosomes to lung, lymph node
      and stroma cells. The present review discussed the possible role of tetraspanins
      in the formation, cargo selection, target selection and uptake of exosomes and
      suggests exciting new directions for future research.

PMID- 29575603
TI  - The Arabidopsis catalase triple mutant reveals important roles of catalases and
      peroxisome-derived signaling in plant development.
AB  - Hydrogen peroxide (H2 O2 ) is generated in many metabolic processes. As a
      signaling molecule, H2 O2 plays important roles in plant growth and development,
      as well as environmental stress response. In Arabidopsis, there are three
      catalase genes, CAT1, CAT2, and CAT3. The encoded catalases are predominately
      peroxisomal proteins and are critical for scavenging H2 O2 . Since CAT1 and CAT3
      are linked on chromosome 1, it has been almost impossible to generate cat1/3 and
      cat1/2/3 mutants by traditional genetic tools. In this study, we constructed
      cat1/3 double mutants and cat1/2/3 triple mutants by CRISPR/Cas9 to investigate
      the role of catalases. The cat1/2/3 triple mutants displayed severe redox
      disturbance and growth defects under physiological conditions compared with wild
      type and the cat2/3 double mutants. Transcriptome analysis showed a more profound
      transcriptional response in the cat1/2/3 triple mutants compared to the cat2/3
      mutants. These differentially expressed genes are involved in plant growth
      regulation as well as abiotic and biotic stress responses. In addition,
      expression of OXI1 (OXIDATIVE SIGNAL INDUCIBLE 1) and several MAPK cascade genes
      were changed dramatically in the catalase triple mutant, suggesting that H2 O2
      produced in peroxisomes could serve as a peroxisomal retrograde signal.

PMID- 29575604
TI  - Synthesis of Branched DNA Scaffolded Super-Nanoclusters with Enhanced
      Antibacterial Performance.
AB  - Metal nanoclusters (NCs) possess unique optical properties, and exhibit a wide
      variety of potential applications. DNA with robust molecular programmability is
      demonstrated as an ideal scaffold to regulate the formation of NCs, offering a
      rational approach to precisely tune the spatial structures of NCs. Herein, the
      first use of branched DNA as scaffold to regulate the formation of silver
      nanoclusters (super-AgNC) is reported, in which the spatial structures are
      precisely designed and constructed. Super-AgNC with tunable shapes and arm
      lengths including Y-, X-, and (Y-X)- shaped super-AgNC is achieved. The molecular
      structures and optical properties of super-AgNCs are systemically studied. As a
      proof of application, remarkably, super-AgNCs exhibit superior antibacterial
      performance. In addition, super-AgNCs show excellent biocompatibility with three
      types of tissue cells including 293T (human embryonic kidney cells), SMCs
      (vascular smooth muscle cells), and GLC-82 (lung adenocarcinoma cells). These
      performances enable the super-AgNCs adaptable in a variety of applications such
      as biosensing, bioimaging, and antibacterial agents.

PMID- 29575605
TI  - Impact of Cavitation, High Shear Stress and Air/Liquid Interfaces on Protein
      Aggregation.
AB  - The reported impact of shear stress on protein aggregation has been
      contradictory. At high shear rates, the occurrence of cavitation or entrapment of
      air is reasonable and their effects possibly misattributed to shear stress. Nine
      different proteins (alpha-lactalbumin, two antibodies, fibroblast growth factor
      2, granulocyte colony stimulating factor [GCSF], green fluorescence protein
      [GFP], hemoglobin, human serum albumin, and lysozyme) are tested for their
      aggregation behavior on vapor/liquid interfaces generated by cavitation and
      compared it to the isolated effects of high shear stress and air/liquid
      interfaces generated by foaming. Cavitation induced the aggregation of GCSF by
      +68.9%, hemoglobin +4%, and human serum albumin +2.9%, compared to a control,
      whereas the other proteins do not aggregate. The protein aggregation behaviors of
      the different proteins at air/liquid interfaces are similar to cavitation, but
      the effect is more pronounced. Air-liquid interface induced the aggregation of
      GCSF by +94.5%, hemoglobin +35.5%, and human serum albumin (HSA) +31.1%. The
      results indicate that the sensitivity of a certain protein toward cavitation is
      very similar to air/liquid-induced aggregation. Hence, hydroxyl radicals cannot
      be seen as the driving force for protein aggregation when cavitation occurs.
      Further, high shear rates of up to 108  s-1 do not affect any of the tested
      proteins. Therefore, also within this study generated extremely high isolated
      shear rates cannot be considered to harm structural integrity when processing
      proteins.

PMID- 29575606
TI  - Gelatin/nano-hydroxyapatite hydrogel scaffold prepared by sol-gel technology as
      filler to repair bone defects.
AB  - This study reports on the development of a scaffold with a gradient of bioactive
      solid signal embedded in the biodegradable polymer matrix by combining a sol-gel
      approach and freeze-drying technology. The chemical approach based on the sol-gel
      transition of calcium phosphates ensures the particles dispersion into the
      gelatin matrix and a direct control of interaction among COOHgelatin /Ca2+ ions.
      Morphological analysis demonstrated that on the basis of the amount of inorganic
      component and by using specific process conditions, it is possible to control the
      spatial distribution of nanoparticles around the gelatin helix. In fact,
      methodology and formulations were able to discriminate between the different
      hydroxyapatite concentrations and their respective morphology. The good
      biological response represented by good cell attachment, proliferation and
      increased levels of alkaline phosphatase as an indicator of osteoblastic
      differentiation of human mesenchymal stem cells toward the osteogenic lineage,
      demonstrating the effect of bioactive solid signals on cellular behavior.
      Furthermore, the inhibition of reactive oxygen species production by composite
      materials predicted potential anti-inflammatory properties of scaffolds thus
      confirming their biocompatibility. Indeed, these interesting biological results
      suggest good potential application of this scaffold as filler to repair bone
      defects. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2007
      2019, 2018.

PMID- 29575607
TI  - Maximum QTc on Holter electrocardiography in children.
AB  - BACKGROUND: Corrected QT interval (QTc) on electrocardiography (ECG) at rest and
      after exercise in a short daytime recording period may be insufficient for the
      diagnosis and management of long QT syndrome (LQTS), especially for LQTS type 2
      and 3. Therefore, examination of QTc on Holter ECG is important. We designed a
      method of analyzing QTc on Holter ECG that can be performed in daily clinical
      practice by combining automatic and manual measurements. METHODS: We reviewed the
      charts of healthy children (n = 210) and LQTS patients (n = 35) aged <16 years
      and analyzed QTc at rest and after exercise, and the maximum QTc on Holter ECG.
      RESULTS: The QTc (Fridericia's correction) of most controls and LQTS patients
      reached the maximum at night or early in the morning. QTc differed according to
      sex and age. In the control group, QTc on ECG of all three types tended to
      lengthen with age. QTc after exercise was slightly longer than QTc at rest, and
      the maximum QTc on Holter ECG was much longer than both, reaching >450 ms in boys
      and 500 ms in girls. In most LQTS type 1 patients, QTc after exercise and that on
      Holter ECG tended to be long. In most LQTS type 2 and 3 patients, QTc at rest and
      that after exercise was long, and that on Holter ECG tended to be much longer.
      CONCLUSIONS: The present method of analyzing QTc on Holter ECG, in which
      automatic and manual measurements are combined, is practical and may be useful
      for diagnosis and risk stratification of LQTS.

PMID- 29575608
TI  - The association between reading abilities and visual-spatial attention in Hong
      Kong Chinese children.
AB  - A growing body of research suggests that visual-spatial attention is important
      for reading achievement. However, few studies have been conducted in non
      alphabetic orthographies. This study extended the current research to reading
      development in Chinese, a logographic writing system known for its visual
      complexity. Eighty Hong Kong Chinese children were selected and divided into poor
      reader and typical reader groups, based on their performance on the measures of
      reading fluency, Chinese character reading, and reading comprehension. The poor
      and typical readers were matched on age and nonverbal intelligence. A Posner's
      spatial cueing task was adopted to measure the exogenous and endogenous orienting
      of visual-spatial attention. Although the typical readers showed the cueing
      effect in the central cue condition (i.e., responses to targets following valid
      cues were faster than those to targets following invalid cues), the poor readers
      did not respond differently in valid and invalid conditions, suggesting an
      impairment of the endogenous orienting of attention. The two groups, however,
      showed a similar cueing effect in the peripheral cue condition, indicating intact
      exogenous orienting in the poor readers. These findings generally supported a
      link between the orienting of covert attention and Chinese reading, providing
      evidence for the attentional-deficit theory of dyslexia.

PMID- 29575610
TI  - A red cell preservation strategy reduces postoperative transfusions in pediatric
      heart surgery patients.
AB  - BACKGROUND: Blood transfusion has well-documented adverse effects. As part of a
      blood conservation initiative at our center, we began routine use of cell saver
      for all congenital heart surgery performed on cardiopulmonary bypass since 2014.
      AIMS: This study aimed to compare transfusion rates prior to, and in the first
      and second year after this initiative. We hypothesized that cell saver use would
      decrease transfusion requirements in second year after use of the cell saver
      compared to the pre cell saver group. METHODS: Consecutive patients under 18
      years undergoing congenital heart surgery on cardiopulmonary bypass were
      retrospectively analyzed as 3 one-year cohorts defined above. We excluded
      patients who required mechanical support or reoperation at index admission.
      Baseline characteristics, and use of blood intraoperatively and postoperatively
      were compared between groups. RESULTS: The 3 groups had similar baseline
      characteristics. Blood use was significantly lower in year 2 after cell saver
      initiation as compared to the pre cell saver group both intra- and
      postoperatively. The median difference in volume of intraoperative blood
      transfusion was lower by 138 mL/m2 (-266, -10 mL/m2 ) in year 2 when compared to
      the pre cell saver group. Similarly, the proportion of subjects requiring red
      blood cell transfusion postoperatively on day of surgery was lower by 10% (-15%, 
      6%). CONCLUSION: Standardized use of cell saver significantly decreased
      perioperative blood use in children undergoing cardiac surgery at our center. A
      risk-adjusted transfusion threshold for children undergoing heart surgery needs
      to be developed to further decrease exposure to blood products and associated
      costs.

PMID- 29575609
TI  - Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1
      promotes lung adenocarcinoma by directly interacting with specificity protein 1.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (malat1) is an oncogenic
      long non-coding RNA (lncRNA) which has been proven to be associated with various
      types of tumors. Transcription factor specificity protein 1 (SP1) is
      overexpressed in many types of cancers. Previously, we observed that malat1
      expression level is regulated by SP1 in lung cancer. In the present study, we
      found that transfection of expression construct of malat1 5' end fragment M5
      enhances stability and transcriptional activity of SP1. Various SP1 target genes
      are also upregulated following overexpression of malat1 M5 in lung adenocarcinoma
      cells. We also showed that malat1 M5 interacts with the C-terminal domain of SP1
      by RNA immunoprecipitation (RIP) assay coupled with UV cross-linking. Malat1-SP1
      association results in increase of SP1 stability. In turn, SP1 promotes malat1
      transcription, thus forming a positive feedback loop. In conclusion, our data
      show that in lung adenocarcinoma cells, malat1 interacts with SP1 protein and
      promotes SP1-mediated transcriptional regulation of SP1 target genes.

PMID- 29575611
TI  - A Mathematical Model for Predicting Obesity Transmission with Both Genetic and
      Nongenetic Heredity.
AB  - OBJECTIVE: Obesity is transmissible across generations through both genetic and
      nongenetic routes, but distinguishing between these factors is challenging. This
      study aimed to quantitatively examine the contribution of these genetic and
      nongenetic effects to assess their influence on obesity prevalence. METHODS: A
      mathematical model was proposed that incorporated both the genetic and nongenetic
      effects of obesity. Model parameters were estimated by using observational data.
      Model simulations were used to assess the sensitivity of model parameters. To
      strengthen the study's approach, parameter estimation and simulation using data
      from the United Kingdom were also performed. RESULTS: Individuals homozygous for
      a "hypothetical obesogenic gene" were suggested to be more susceptible to both
      socially contagious risk and spontaneous weight gain risk. The model predicted
      that obesity prevalence would reach 41.03% (39.28, 44.31) and 26.77% (25.62,
      28.06) at 2030 in the United States and United Kingdom, respectively. The
      socially contagious risk factor had a greater overall impact on the distribution
      of the population with obesity than did spontaneous weight gain risk or mother-to
      child obesity transmission risk. CONCLUSIONS: Although the proposed "first
      approximation" model captured the complex interactions between the genetic and
      nongenetic effects on obesity, this framework remains incomplete. Future work
      should incorporate other key features driving the obesity epidemic.

PMID- 29575612
TI  - Assessment of the metabolism and morphology of the porcine cornea, lens and
      retina by 2-photon imaging.
AB  - Two-photon imaging is a noninvasive imaging technique with increasing importance
      in the biological and medical fields since it allows intratissue cell imaging
      with high resolution. We demonstrate the feasibility of using a single 2-photon
      instrument to evaluate the cornea, the crystalline lens and the retina based on
      their autofluorescence (AF). Image acquisition was performed using a custom-built
      2-photon microscope for 5-dimensional microscopy with a near infrared broadband
      sub-15 femtosecond laser centered at 800 nanometers. Signals were detected using
      a spectral photomultiplier tube. The spectral ranges for the analysis of each
      tissue/layer AF were determined based on the spectra of each tissue as well as of
      pure endogenous fluorophores. The cornea, lens and retina are characterized at
      multiple depths with subcellular resolution based on their morphology and AF
      lifetime. Additionally, the AF lifetime of NAD(P)H was used to assess the
      metabolic activity of the cornea epithelium, endothelium and keratocytes. The
      feasibility to evaluate the metabolic activity of lens epithelial cells was also
      demonstrated, which may be used to further investigate the pathogenesis of
      cataracts. The results illustrate the potential of multimodal multiphoton imaging
      as a novel ophthalmologic technique as well as its potential as a diagnostic
      tool.

PMID- 29575613
TI  - Humanization of fibroblast growth factor 1 single-chain antibody and validation
      for its antitumorigenic efficacy in breast cancer and glioma cells.
AB  - Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins
      with high antigen-binding affinity. We have previously reported that fibroblast
      growth factor 1 played pivotal roles in cancer development and generated a mouse
      scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and
      in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided
      complementarity determining region grafting strategy. The purified hscFv1C9
      maintained similar antigen-binding affinity and specificity as mscFv1C9, and it
      was capable of inhibiting growth of different tumours in vitro and in vivo. These
      data strongly suggested that hscFv1C9 has antitumour potentials.

PMID- 29575614
TI  - Combination of RIZ1 Overexpression and Radiotherapy Contributes to Apoptosis and
      DNA Damage of HeLa and SiHa Cervical Cancer Cells.
AB  - Although radiotherapy has been widely applied to treating cervical cancer in the
      clinic, its therapeutic efficacy is often restricted to the radioresistance of
      cancer cells. Retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) has
      been suggested as a tumour suppressor gene, whereas its role in cervical cancer
      with or without radiotherapy has been unclear. In this study, two cervical cancer
      cell lines, HeLa and SiHa cells, stably transfected with RIZ1 overexpression
      plasmid were subjected to ionizing radiation, and their survival fractions were
      calculated by assessing their clonogenic abilities. Our results showed that the
      forced overexpression of RIZ1 significantly reduced the clonogenic survival rates
      of both HeLa and SiHa cells exposed to ionizing radiation. By analysing the cell
      apoptotic status, we found that the RIZ1-overexpressed cervical cancer cells
      under ionizing radiation were more vulnerable to damage, and more gamma-H2AX foci
      were found in these cells. Furthermore, the volumes of tumour xenografts formed
      by the RIZ1-overexpressed cells in nude mice under ionizing radiation were
      smaller than those generated by the control cells. There were more morphological
      changes, apoptosis cells and lower expression of PCNA in RIZ1-overexpressed
      tumour tissues of mice after exposure to ionizing radiation. Taken together, our
      study demonstrates that the overexpression of RIZ1 combined with radiotherapy
      facilitates apoptosis and DNA damage of cervical cancer cells.

PMID- 29575615
TI  - Spectrum of hemostatic disorders in Indian females presenting with bleeding
      manifestations.
AB  - INTRODUCTION: Hemostatic disorders are often missed in women with bleeding
      particularly menorrhagia. Preexisting hemostatic disorders are now known as
      common risk factor for postpartum hemorrhage and prolonged bleeding in
      puerperium. Females with bleeding complaints constitute an important population
      referred to hematology clinic. Hence, we aim to evaluate the type and frequency
      of hemostatic disorders among females presenting with bleeding in a tertiary care
      hospital and a basic hemostatic laboratory. METHODS: Three-year data were
      retrospectively analyzed for 200 females with various bleeding complaints. Due to
      resource constraints, a hemostatic workup was done with prothrombin time,
      activated partial thromboplastin time, thrombin time, fibrinogen assay, clot
      solubility test, mixing studies, specific factor assays, platelet function test,
      and von Willebrand factor antigen level. RESULTS: A total of 200 females were
      investigated to identify the cause of their bleeding. Thirty-five of 200 (17.5%)
      females were found with an underlying bleeding disorder. Of these 35 females,
      65.7% presented with bleeding from more than 1 site. Most common bleeding
      manifestation was spontaneous bruising in 18 of 35 (51.4%) patients followed by
      petechiae (48.6%). Inherited bleeding disorders were noted in majority. The most
      common inherited bleeding disorder identified was von Willebrand disease (VWD) in
      34.3% females. Second most common disorder was Glanzmann's thrombasthenia
      accounting for 22.8%. Rare coagulation factor deficiency, such as factors VII, X,
      and XIII deficiencies, was noted. Three cases revealed acquired causes of
      coagulation defects. CONCLUSION: Underlying hemostatic defects should be searched
      for in women with unexplained bleeding complaints. This will not only help in
      diagnosis but also in proper management for future hemostatic challenges.

PMID- 29575616
TI  - Autosomal dominant Robinow syndrome associated with a novel DVL3 splice mutation.
AB  - Robinow syndrome is a clinically and genetically heterogeneous disorder
      characterized by mesomelic limb shortening, distinctive facial features, and
      variable oral, cardiac, vertebral, and urogenital malformations. We identified
      the novel de novo splice acceptor mutation c.1715-2A > C in DVL3 in a 15-year-old
      female patient with typical features of Robinow syndrome. By studying DVL3
      transcripts in this patient, we confirmed expression of both wild-type and mutant
      alleles. Mutant DVL3 mRNAs were found to harbor a deletion of four nucleotides at
      the beginning of exon 15 and encode a protein product with a distinct -1 reading
      frame C-terminus. The data demonstrate that mutant DVL3 proteins associated with
      Robinow syndrome show truncation of the C-terminus and share 83 novel amino acid
      residues before the stop codon confirming highly specific DVL3 alterations to be
      associated with this syndrome. The phenotype of the Robinow syndrome-affected
      female reported here is typical as she shows mesomelia and mild hand anomalies as
      well as characteristic facial anomalies. She also exhibited a supraumbilical
      midline abdominal raphe which has not been observed in other patients with
      Robinow syndrome. In contrast to the clinical data of four previously reported
      individuals with DVL3-related Robinow syndrome, short stature was not present in
      this individual at the age of 15 years. These findings expand the clinical
      spectrum of Robinow syndrome associated with DVL3 mutations. To date, comparison
      of clinical data of DVL3 mutation-positive individuals with those of patients
      with genetically different forms did not allow delineation of gene-specific
      phenotypes.

PMID- 29575617
TI  - Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with
      palmoplantar keratoderma: A review of literature and expansion of clinical
      phenotype.
AB  - Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal
      (MIM # 610644) is a clinically distinctive form of SRY-negative 46,XX disorder of
      sex development. It is a rare autosomal recessive disorder caused due to
      biallelic loss of function mutations in RSPO1 gene. RSPO1 acts by activating the
      canonical beta-catenin pathway and is one of the most important genes controlling
      female gonadal differentiation. RSPO1-associated disorders of sex development
      have been described only in three instances in the past. We report fourth such
      case with additional findings and perform a comparative review of previous
      phenotypic descriptions, thereby expanding the clinical phenotype of this
      syndrome.

PMID- 29575618
TI  - A homozygous TTN gene variant associated with lethal congenital contracture
      syndrome.
AB  - Pathogenic variants in the TTN gene have been reported to cause various
      cardiomyopathies and a range of skeletal muscle diseases, collectively known as
      titinopathies. We evaluated a consanguineous family multiple members affected
      with a lethal congenital contracture syndrome. Using exome sequencing, we
      identified a homozygous c.36122delC (p. P12041Lfs*20) variant in exon 167 in the
      fetal IC isoform of TTN. The finding expands the phenotypes that can be caused by
      pathogenic variants TTN, which should be considered in lethal congenital
      contracture syndromes, arthrogryposis multiplex congenita, congenital myopathies,
      and hydrops fetalis.

PMID- 29575619
TI  - DNA Methylation Possible Adjunct to Screening for Neurodevelopmental Syndromes:
      DNA methylation signatures were identified for several neurodevelopmental
      Mendelian disorders, and hold promise as a supplement to standard procedures for
      screening and detection of these diseases.

PMID- 29575620
TI  - Age and ASD symptoms in Costello syndrome.

PMID- 29575621
TI  - Associations between laterality of orofacial clefts and medical and academic
      outcomes.

PMID- 29575623
TI  - Low serum fatty acid levels in pregnancies with fetal gastroschisis: A
      prospective study.
AB  - Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of
      abdominal organs. The underlying cause of the disease remains unknown; however,
      studies suggest that nutritional factors may play a role in its development. This
      prospective case-control study explored the association of serum fatty acid
      levels of pregnant women and occurrence of gastroschisis. Gastroschisis group
      comprised 57 pregnant women with fetuses with gastroschisis, and the control
      group comprised 114 pregnant women with normal fetuses. Serum fatty acids levels
      were compared between the groups for the overall pregnancy at <34 weeks; <=25
      weeks, and >25 and <34 weeks; and at delivery. Total fatty acids (p = .008),
      unsaturated fatty acids (p = .002), and the C18:1n9/C18:00 ratio (p = .021) were
      lower in the gastroschisis group than in the control group during the overall
      pregnancy; however, the C16:00/C18:2n6 ratio (p = .018) was higher in the
      gastroschisis group than in the control group during the same period. Total fatty
      acids (p = .044) and unsaturated fatty acids (p = .024) were lower in the
      gastroschisis group at <=25 weeks, and unsaturated fatty acid (p = .025) and the
      C18:1n9/C18:00 ratio (p = .013) were lower in the gastroschisis group than in the
      control group at >25 and <34 weeks. Pregnant women with fetuses with
      gastroschisis have low serum fatty acids levels during pregnancy. These findings
      suggest that fatty acids levels may be involved in the pathogenesis of fetal
      gastroschisis.

PMID- 29575622
TI  - Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome.
AB  - Clinical molecular testing has been available for 22q11.2 deletion syndrome
      (22q11.2DS) for over two decades yet under-recognition and diagnostic delays are
      common. To characterize the "diagnostic odyssey" in 22q11.2DS we studied 202 well
      characterized unrelated adults, none ascertained through an affected relative. We
      used a regression model to identify clinical and demographic factors associated
      with length of time to molecular diagnosis. Kaplan-Meier analysis compared time
      to diagnosis for the molecular testing era (since 1994) and earlier birth
      cohorts. The results showed that the median time to molecular diagnosis of the
      22q11.2 deletion was 4.7 (range 0-20.7) years. Palatal and cardiac anomalies, but
      not developmental delay/intellectual disability, were associated with a shorter
      time to molecular diagnosis. Non-European ethnicity was associated with longer
      time to diagnosis. Inclusion of a cohort from another 22q11.2DS center increased
      power to observe a significantly earlier diagnosis for patients born in the
      molecular testing era. Nonetheless, only a minority were diagnosed in the first
      year of life. On average, patients were seen in seven (range 2-15) different
      clinical specialty areas prior to molecular diagnosis. The findings indicate that
      even for those born in the molecular testing era, individuals with 22q11.2DS and
      their families face a diagnostic odyssey that is often prolonged, particularly in
      the absence of typical physical congenital features or for those of non-European
      ancestry. The results support educational efforts to improve clinical recognition
      and testing, and ultimately newborn screening as a means of maximizing early
      detection that would provide the best opportunity to optimize outcomes.

PMID- 29575624
TI  - First-year growth in children with Noonan syndrome: Associated with feeding
      problems?
AB  - Children with Noonan syndrome show rapid decline of growth in the first year of
      life and feeding problems are present in over 50%. The aim of this study was to
      explore whether growth decelerates because of feeding problems or other Noonan
      syndrome-related factors. We performed a retrospective, longitudinal cohort study
      of clinically and genetically diagnosed subjects with Noonan syndrome (n = 143).
      Questionnaires about the phenotypic-genotypic profile and reported feeding
      problems were sent to eligible subjects. Data on first-year growth was obtained
      from growth charts. Ninety-one participants were excluded because of different
      criteria. A total of 52 subjects with Noonan syndrome were included. The largest
      decline in weight and length standard deviation score (SDS) occurred in the first
      2.5 months after birth (-1.93 and -1.15, respectively), with feeding problems
      causing a decline of 0.57 SDS in the remaining months. At 1 year, children with
      feeding problems were on average 290 g lighter and 0.8 cm shorter than children
      without feeding problems. Weight gain was also negatively influenced by having a
      PTPN11 mutation (n = 39) and a higher gestational age, whereas children of
      parents with Noonan syndrome and with a higher birth weight gained more weight.
      Growth in length was reduced by having cardiac surgery and a higher gestational
      age, but positively influenced by birth length and maternal height. Growth in
      children with Noonan syndrome is impaired right after birth and only partially
      associated with feeding problems. In addition, several specific Noonan syndrome
      related factors seem to influence growth in the first year.

PMID- 29575626
TI  - Challenges associated with parenting youth with neurofibromatosis: A qualitative
      investigation.
AB  - Parents of children with the neurofibromatoses (NF; neurofibromatosis 1,
      neurofibromatosis 2, and schwannomatosis) are at an increased risk for emotional
      and physical health problems. This study aimed to determine parents' perceptions
      of stressors associated with parenting a child with NF in order to inform the
      development of a resiliency intervention. We conducted three live video semi
      structured focus groups with parents of youth with NF (N = 30), which were
      subsequently transcribed and coded using qualitative content analysis. Parents
      reported heightened stress associated with the child's educational, medical, and
      social needs, as well as concerns about their child's physical and mental health.
      They also reported stress associated with managing finances, multiple medical
      appointments, role challenges (i.e., being a parent or partner), and managing the
      uncertainty/unpredictability of their child's NF diagnosis. These stressors
      reportedly affected employment status (i.e., work scale backs), relationships
      (i.e., social, familial, with partner, other children), and the parents' physical
      and mental health. All participants expressed interest in a mind body program
      aimed at improving resiliency by teaching coping skills (e.g., mindfulness,
      adaptive thinking, positive psychology skills) and enhancing social support.
      Results show parents' enthusiasm for a resiliency intervention targeting stress
      associated with parenting a child with NF, and provide valuable information for
      the content of the intervention and its delivery modality.

PMID- 29575627
TI  - A recurrent mutation causing Melnick-Needles syndrome in females confers a
      severe, lethal phenotype in males.
AB  - Melnick-Needles syndrome (MNS; MIM 309350) is an X-linked skeletal dysplasia
      caused by mutations in FLNA. Females with the condition present with
      characteristic facial features, short stature, skeletal anomalies, including
      poorly modeled and sclerotic bones, and structural abnormalities such as cardiac
      and urological defects. Previously males were thought to present with either a
      mild phenotype compatible with life or a severe lethal presentation depending on
      the maternal phenotype. The discovery of a limited number of mutations in FLNA as
      the cause of the condition has clarified the molecular basis of the disorder, but
      only a very small number of severely affected males have been reported with MNS.
      Furthermore, no mildly affected males have been described with a molecular
      confirmation of the condition. In this report, we describe the clinical and
      molecular findings of a mildly affected mother with MNS and her severely affected
      son. They shared a well-documented disease-causing variant in FLNA,
      p.(Ala1188Thr), one of two highly recurrent mutations leading to the disorder.
      This is only the fourth report of a male with perinatal lethal MNS and a
      molecular confirmation; it is the first description of this specific mutation in
      a male.

PMID- 29575628
TI  - Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in
      a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys).
AB  - Congenital sodium diarrhea is a rare and life-threatening disorder characterized
      by a severe, secretory diarrhea containing high concentrations of sodium, leading
      to hyponatremia and metabolic acidosis. It may occur in isolation or in
      association with systemic features such as facial dysmorphism, choanal atresia,
      imperforate anus, and corneal erosions. Mutations in the serine protease
      inhibitor, Kunitz-Type 2 (SPINT2) gene have been associated with congenital
      sodium diarrhea and additional syndromic features. We present a child with
      congenital sodium diarrhea, cleft lip and palate, corneal erosions, optic nerve
      coloboma, and intermittent exotropia who was found to have biallelic mutations in
      SPINT2. One mutation, c.488A > G, predicting p.(Tyr163Cys), has been previously
      associated with a syndromic form of congenital sodium diarrhea. The other
      mutation, c.166_167dupTA, predicting p.(Asn57Thrfs*24) has not previously been
      reported and is likely a novel pathogenic variant for this disorder. We found
      only one other report of an optic nerve coloboma associated with SPINT2 mutations
      and this occurred in a patient with congenital tufting enteropathy. Our patient
      confirms an association of ocular coloboma with presumed loss of SPINT2 function.

PMID- 29575629
TI  - Three novel GJB2 (connexin 26) variants associated with autosomal dominant
      syndromic and nonsyndromic hearing loss.
AB  - Connexin 26 (Cx26), encoded by the GJB2 gene, is a key protein involved in the
      formation of gap junctions in epithelial organs including the inner ear and
      palmoplantar epidermis. Pathogenic variants in GJB2 are responsible for
      approximately 50% of inherited sensorineural deafness. The majority of these
      variants are associated with autosomal recessive inheritance; however, rare
      reports of dominantly co-segregating variants have been published. Since we began
      offering GJB2 testing in 2003, only about 2% of detected GJB2 variants from our
      laboratory have been classified as dominant. Here we report three novel dominant
      GJB2 variants (p.Thr55Ala, p.Gln57_Pro58delinsHisSer, and p.Trp44Gly); two
      associated with syndromic sensorineural hearing loss and one with nonsyndromic
      hearing loss. In the kindred with the p.Thr55Ala variant, the proband and his
      father present with only leukonychia as a cutaneous finding of their syndromic
      hearing loss. This phenotype has been previously documented in conjunction with
      palmoplantar hyperkeratosis, but isolated leukonychia is a novel finding likely
      associated with the unique threonine to alanine change at codon 55 (other
      variants at this codon have been reported in cases of nonsyndromic hearing loss).
      This report contributes to the short list of GJB2 variants associated with
      autosomal dominant hearing loss, highlights the variability of skin and nail
      findings associated with such cases, and illustrates the occurrence of both
      syndromic and nonsyndromic presentations with changes in the same gene.

PMID- 29575630
TI  - Isosorbide dinitrate in nephronophthisis treatment.
AB  - Nephronophthisis is a progressive disease that affects development of the renal
      tubules and leads to end stage renal disease. Many affected children have
      isolated renal disease; however, there can be additional manifestations including
      heart defects, liver fibrosis, brain malformations, and situs inversus. There is
      no way to slow or modify the disease. We describe a patient who presented at
      birth with cholestatic jaundice and decreased kidney function, found by exome
      sequencing to have two NPHP3 variants. Her clinical status deteriorated rapidly,
      and two disease-modifying agents were given in hopes of slowing disease
      progression, the arginine vasopressin type II receptor antagonist tolvaptan to
      stabilize her renal function and isosorbide dinitrate to manage her poorly
      controlled hypertension. Tolvaptan therapy initiated at 82 days of life had
      limited effect on the rate of decline in renal function and was insufficient to
      abrogate the need for dialysis; however, isosorbide dinitrate therapy led to a
      dramatic improvement in blood pressure control and allowed for the
      discontinuation of multiple anti-hypertensive agents. This is the first report of
      the use of tolvaptan and isosorbide dinitrate for nephronophthisis management. We
      suggest that isosorbide dinitrate may represent a disease-modifying agent in
      nephronophthisis treatment.

PMID- 29575631
TI  - Biallelic loss-of-function WNT5A mutations in an infant with severe and atypical
      manifestations of Robinow syndrome.
AB  - Robinow syndrome (RS) is a well-recognized Mendelian disorder known to
      demonstrate both autosomal dominant and autosomal recessive inheritance. Typical
      manifestations include short stature, characteristic facies, and skeletal
      anomalies. Recessive inheritance has been associated with mutations in ROR2 while
      dominant inheritance has been observed for mutations in WNT5A, DVL1, and DVL3.
      Through trio whole genome sequencing, we identified a homozygous frameshifting
      single nucleotide deletion in WNT5A in a previously reported, deceased infant
      with a unique constellation of features comprising a 46,XY disorder of sex
      development with multiple congenital malformations including congenital
      diaphragmatic hernia, ambiguous genitalia, dysmorphic facies, shortened long
      bones, adactyly, and ventricular septal defect. The parents, who are both
      heterozygous for the deletion, appear clinically unaffected. In conjunction with
      published observations of Wnt5a double knockout mice, we provide evidence for the
      possibility of autosomal recessive inheritance in association with WNT5A loss-of
      function mutations in RS.

PMID- 29575632
TI  - Newly described recessive MYH11 disorder with clinical overlap of Multisystemic
      smooth muscle dysfunction and Megacystis microcolon hypoperistalsis syndromes.
AB  - We describe a neonatal patient with fixed dilated pupils and pulmonary, bladder,
      and bowel dysfunction suspicious for the presence of ACTA2 R179 mediated
      multisystemic smooth muscle dysfunction syndrome. Whole exome sequencing revealed
      compound heterozygous mutations in MYH11 after ACTA2 specific testing revealed no
      abnormalities. The child lived until 18 months of age and represents the only
      reported case of an MYH11 compound heterozygote with widespread smooth muscle
      dysfunction.

PMID- 29575633
TI  - Patients Express Satisfaction, Understanding of Whole-Genome Sequencing: In
      primary care and cardiology, patients were generally satisfied with their
      physicians' communication of WGS results, but expectations about its clinical
      benefits were not met.

PMID- 29575634
TI  - Impact of intravenous thrombolysis and emergent carotid stenting on reperfusion
      and clinical outcomes in patients with acute stroke with tandem lesion treated
      with thrombectomy: a collaborative pooled analysis.
AB  - BACKGROUND AND PURPOSE: Tandem anterior circulation lesions in the setting of
      acute ischemic stroke (AIS) are a complex endovascular situation that has not
      been specifically addressed in trials. We determined the predictors of successful
      reperfusion and good clinical outcome at 90 days after mechanical thrombectomy
      (MT) in patients with AIS with tandem lesions in a pooled collaborative study.
      METHODS: This was a retrospective analysis of consecutive patients presenting to
      18 comprehensive stroke centers with AIS due to tandem lesion of the anterior
      circulation who underwent MT. RESULTS: A total of 395 patients were included.
      Successful reperfusion (modified thrombolysis in cerebral infarction score 2b-3)
      was achieved in 76.7%. At 90 days, 52.2% achieved a good outcome (modified Rankin
      Scale score 0-2), 13.8% suffered a parenchymal hematoma and 13.2% were dead.
      Lower National Institutes of Health Stroke Scale score [odds ratio (OR), 1.26;
      95% confidence intervals (CI), 1.07-1.48, P = 0.004], Alberta Stroke Program
      Early CT Score >=7 (OR, 2.00; 95% CI, 1.07-3.43, P = 0.011), intravenous
      thrombolysis (OR, 1.47; 95% CI, 1.01-2.12, P = 0.042) and stenting of the
      extracranial carotid lesion (OR, 1.63; 95% CI, 1.04-2;53, P = 0.030) were
      independently associated with successful reperfusion. Lower age (OR, 1.58; 95%
      CI, 1.26-1.97, P < 0.001), absence of hypercholesterolemia (OR, 1.77; 95% CI,
      1.10-2.84, P = 0.018), lower National Institutes of Health Stroke Scale scores
      (OR, 2.04; 95% CI, 1.53-2.72, P < 0.001), Alberta Stroke Program Early CT Score
      >=7 (OR, 2.75; 95% CI, 1.24-6.10, P = 0.013) and proximal middle cerebral artery
      occlusion (OR, 1.59; 95% CI, 1.03-2.44, P = 0.035) independently predicted a good
      90-day outcome. CONCLUSIONS: Intravenous thrombolysis and emergent stenting of
      the extracranial carotid lesion were predictors of a successful reperfusion after
      MT of patients with AIS with tandem lesion of the anterior circulation.

PMID- 29575636
TI  - Interactions of Fullerene-Polyglycerol Sulfates at Viral and Cellular Interfaces.
AB  - Understanding the mechanism of interactions of nanomaterials at biointerfaces is
      a crucial issue to develop new antimicrobial vectors. In this work, a series of
      water-soluble fullerene-polyglycerol sulfates (FPS) with different
      fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate
      branches are synthesized, characterized, and their interactions with two distinct
      surfaces displaying proteins involved in target cell recognition are
      investigated. The combination of polyanionic branches with a solvent exposed
      variable hydrophobic core in FPS proves to be superior to analogs possessing only
      one of these features in preventing interaction of vesicular stomatitis virus
      coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of
      host cell. Interference with L-selectin-ligand binding is dominated by the
      negative charge, which is studied by two assays: a competitive surface plasmon
      resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on
      ligands under flow conditions. Due to possible intrinsic hydrophobic and
      electrostatic effects of synthesized compounds, pico- to nanomolar half maximal
      inhibitory concentrations (IC50 ) are achieved. With their highly antiviral and
      anti-inflammatory properties, together with good biocompatibility, FPS are
      promising candidates for the future development towards biomedical applications.

PMID- 29575637
TI  - Effect of rosuvastatin on risk markers for venous thromboembolism in cancer.
AB  - : Essentials Statins lower venous thromboembolism risk in general but have not
      been studied in cancer patients. We completed a randomized trial of rosuvastatin
      vs. placebo among cancer patients on chemotherapy. Rosuvastatin did not
      significantly lower prothrombotic biomarkers including D-dimer. The role of
      statins in venous thrombosis prevention in cancer patients remains unknown.
      SUMMARY: Background Statin therapy is associated with lower risk of venous
      thromboembolism (VTE) but has not been prospectively evaluated in patients with
      advanced cancer. Objectives We determined if statin administration in this high
      risk population reduces the risk of VTE, based on established and emerging
      biomarkers. Patients/Methods This double-blind, crossover, randomized controlled
      trial among patients with advanced cancer receiving systemic therapy allocated
      participants to rosuvastatin 20 mg daily or placebo for 3-4 weeks prior to
      crossover to the alternative therapy, with a 3-5-week washout. D-dimer, C
      reactive protein (CRP), soluble (s)P-selectin, factor VIII (FVIII), thrombin
      generation and exploratory biomarkers focusing on endogenous thrombin potential,
      including tissue factor (TF), activated factor IX (FIXa) and activated factor XI
      (FXIa), were measured at the start and end of both treatment periods. The primary
      outcome was change in D-dimer with rosuvastatin compared with placebo. Results Of
      38 enrolled participants, 24 (63%) completed the study. Rosuvastatin did not
      cause statistically significant changes in D-dimer levels or any other biomarker.
      CRP levels decreased by 40%; 4.3 mg L-1 (95% confidence interval, -11.0 to +2.5
      mg L-1 ) compared with placebo. In post-hoc analysis, participants who received
      rosuvastatin initially during their first line of treatment had a 13% decrease in
      D-dimer. Circulating TF, FIXa and FXIa were detected in 26%, 68% and 71% of
      cancer patients despite not being found in healthy individuals. Conclusions
      Rosuvastatin did not cause favorable changes in biomarkers of VTE risk in
      advanced cancer patients receiving chemotherapy. The role of statin therapy as
      thromboprophylaxis in the cancer population remains uncertain.

PMID- 29575635
TI  - Biomarkers as Common Data Elements for Symptom and Self-Management Science.
AB  - PURPOSE: Biomarkers as common data elements (CDEs) are important for the
      characterization of biobehavioral symptoms given that once a biologic moderator
      or mediator is identified, biologically based strategies can be investigated for
      treatment efforts. Just as a symptom inventory reflects a symptom experience, a
      biomarker is an indicator of the symptom, though not the symptom per se. The
      purposes of this position paper are to (a) identify a "minimum set" of biomarkers
      for consideration as CDEs in symptom and self-management science, specifically
      biochemical biomarkers; (b) evaluate the benefits and limitations of such a
      limited array of biomarkers with implications for symptom science; (c) propose a
      strategy for the collection of the endorsed minimum set of biologic samples to be
      employed as CDEs for symptom science; and (d) conceptualize this minimum set of
      biomarkers consistent with National Institute of Nursing Research (NINR) symptoms
      of fatigue, depression, cognition, pain, and sleep disturbance. DESIGN AND
      METHODS: From May 2016 through January 2017, a working group consisting of a
      subset of the Directors of the NINR Centers of Excellence funded by P20 or P30
      mechanisms and NINR staff met bimonthly via telephone to develop this position
      paper suggesting the addition of biomarkers as CDEs. The full group of Directors
      reviewed drafts, provided critiques and suggestions, recommended the minimum set
      of biomarkers, and approved the completed document. Best practices for selecting,
      identifying, and using biological CDEs as well as challenges to the use of
      biological CDEs for symptom and self-management science are described. Current
      platforms for sample outcome sharing are presented. Finally, biological CDEs for
      symptom and self-management science are proposed along with implications for
      future research and use of CDEs in these areas. FINDINGS: The recommended minimum
      set of biomarker CDEs include pro- and anti-inflammatory cytokines, a
      hypothalamic-pituitary-adrenal axis marker, cortisol, the neuropeptide brain
      derived neurotrophic factor, and DNA polymorphisms. CONCLUSIONS: It is
      anticipated that this minimum set of biomarker CDEs will be refined as knowledge
      regarding biologic mechanisms underlying symptom and self-management science
      further develop. The incorporation of biological CDEs may provide insights into
      mechanisms of symptoms, effectiveness of proposed interventions, and
      applicability of chosen theoretical frameworks. Similarly, as for the previously
      suggested NINR CDEs for behavioral symptoms and self-management of chronic
      conditions, biological CDEs offer the potential for collaborative efforts that
      will strengthen symptom and self-management science. CLINICAL RELEVANCE: The use
      of biomarker CDEs in biobehavioral symptoms research will facilitate the
      reproducibility and generalizability of research findings and benefit symptom and
      self-management science.

PMID- 29575638
TI  - Improving bone marrow biopsy quality through peer discussion and data
      comparisons: A single institution experience.
AB  - INTRODUCTION: Bone marrow biopsy (BMB) is crucial for the diagnosis, staging, and
      monitoring of a variety of hematologic diseases. Obtaining an adequate BMB can be
      challenging given the need to balance patient comfort with acquisition of high
      quality specimens. We had observed variable BMB quality at our institution with
      poor quality specimens sometimes affecting diagnosis. We thus undertook this
      quality improvement (QI) project to improve the quality of diagnostic BMB
      specimens. METHODS: We used an A3 QI process to identify factors possibly
      influencing BMB quality. We collected baseline data on 211 BMB, with short and
      long-term follow-up data on a further 382 cases. We used clinical conferences to
      discuss data, perform peer comparisons and identify strategies to create a
      sustainable improvement in BMB quality. RESULTS: Baseline data showed that BMB
      length was influenced most by the individual performer, with some influence of
      needle gauge. Other factors such as sedation, BMB indication were
      noncontributory. BMB lengths improved following performer education and
      individual performer data comparisons (15.2 mm post vs 12.8 mm baseline, P <
      .0001) and with use of an 8- rather than 11-gauge needle (18.3 mm 8-gauge vs 13.3
      mm 11-gauge P < .0001), and were sustained over the long term. CONCLUSIONS:
      Education on BMB standards, sharing of performer data, and changing needle gauge
      are relatively straightforward methods to improve BMB quality, leading to easier
      pathology diagnosis.

PMID- 29575639
TI  - Recurrent inhibition is higher in eccentric compared to isometric and concentric
      maximal voluntary contractions.
AB  - AIM: This study was designed to investigate the influence of muscle contraction
      type on spinal recurrent inhibition during maximal voluntary contractions (MVC)
      of the plantar flexor muscles. METHODS: To that purpose, the paired Hoffmann
      reflex (H-reflex) technique permitted to assess changes in recurrent pathway by
      comparing the modulations of test, reference and conditioning H-reflexes (H',
      Href and H1 respectively) in the soleus muscle during isometric, concentric and
      eccentric MVC. Twenty-five subjects participated in an experimental session
      designed to assess the activity of the recurrent inhibition pathway. RESULTS: The
      results indicate that both the electromyographic activity and the amplitude of H1
      normalized to the maximal M-wave (Mmax ) were similar regardless of the muscle
      contraction type while the ratio between H' and H1 amplitudes was significantly
      smaller during eccentric compared with isometric and concentric MVC. Furthermore,
      Href and H' amplitudes did not differ significantly during both isometric and
      concentric MVCs while H' amplitude was significantly lower than Href amplitude
      during eccentric MVC. In addition, the V/Mmax ratio was similar for all muscle
      contraction type and greater H' amplitude was significantly correlated with
      greater V-wave amplitude regardless of the muscle contraction type. CONCLUSION:
      Together, the current results indicate that recurrent inhibition is elevated for
      the soleus muscle during eccentric compared to isometric and concentric MVC. Data
      further suggest that the Renshaw cell activity is specifically controlled by the
      descending neural drive and/or peripheral neural mechanisms during eccentric MVC.

PMID- 29575640
TI  - Potentially traumatic events in youth with and at clinical high risk for
      psychosis.
AB  - AIM: Previous research has demonstrated a strong association between early trauma
      exposure and the development of psychotic symptoms. However, few of these studies
      have included young adolescents and children. This study investigated rates and
      number of potentially traumatic experiences (PTEs) among typically developing
      youth (TD; n = 21), youth at clinical high risk for psychosis (CHR; n = 38), and
      youth with a psychotic disorder (PD; n = 28) between 7 and 18 years of age. CHR
      participants were further evaluated to determine whether a history of PTEs was
      associated with prodromal symptom severity. METHODS: Study group inclusion was
      determined by structured interviews. Trauma history was assessed using the post
      traumatic stress disorder module of the Schedule for Affective Disorders and
      Schizophrenia for School-Age Children-Present and Lifetime Version. CHR
      participants with vs without a history of PTEs were compared on severity of
      prodromal symptoms. RESULTS: CHR and PD participants reported significantly
      higher rates and numbers of PTEs than TD participants. Contrary to expectations
      and prior research, CHR participants with vs without a history of PTEs did not
      differ in prodromal symptom severity. Explanations and implications for the
      findings are discussed. CONCLUSIONS: These findings suggest that the relationship
      between trauma and the development of psychotic symptoms extends to children and
      adolescents as young as 7 years of age. This study underscores the importance of
      screening for trauma exposure among youth seeking treatment for psychotic
      symptoms.

PMID- 29575641
TI  - NT-pro BNP-A marker for worsening respiratory status and mortality in infants and
      young children with pulmonary hypertension.
AB  - AIM: To evaluate predictors of morbidity and mortality in pediatric patients with
      pulmonary hypertension (PH), laboratory and echocardiographic measures of PH were
      analyzed. METHODS: A retrospective review of all infants and children < 2 years
      of age with PH from January 2011 to August 2016 was conducted. Correlations were
      determined using Spearman's rank correlation coefficients. Differences in
      characteristics between survivors and nonsurvivors were analyzed and Kaplan-Meier
      survival curves were generated. RESULTS: Of 56 patients, the majority were
      extremely premature; of African American ethnicity; and had bronchopulmonary
      dysplasia. Patients who died were more likely to have underlying congenital heart
      disease; have a higher increase in the concentration of carbon dioxide in the
      blood (pCO2 ) with a corresponding greater mean percentage decrease in pH and
      percentage rise in NT-pro BNP during PH exacerbations; more likely to have been
      on medications for pulmonary hypertension; and have a higher RVSP/SBP (%) ratio
      and S/D ratio. There were positive correlations between percentage rise in NT-pro
      BNP and pCO2 ; NT-pro BNP and RVSP/SBP (%) ratio; and RVSP/SBP (%) ratio and S/D
      ratio. CONCLUSIONS: Infants and young children with pulmonary hypertension have
      increased morbidity and mortality. NT-pro BNP is a useful biomarker for both
      respiratory exacerbations and mortality, and RVSP/SBP (%) ratio and S/D ratio are
      echocardiographic identifiers for increased mortality.

PMID- 29575642
TI  - Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Total
      Synthesis of (-)-17-nor-Excelsinidine.
AB  - We report the first total synthesis of (-)-17-nor-excelsinidine, a zwitterionic
      monoterpene indole alkaloid that displays an unusual N4-C16 connection. Inspired
      by the postulated biosynthesis, we explored an oxidative coupling approach from
      the geissoschizine framework to forge the key ammonium-acetate connection. Two
      strategies allowed us to achieve this goal, namely an intramolecular nucleophilic
      substitution on a 16-chlorolactam with the N4 nitrogen atom or a direct I2 
      mediated N4-C16 oxidative coupling from the enolate of geissoschizine.

PMID- 29575643
TI  - Creating a framework for the prioritization of biosecurity risks to the New
      Zealand dairy industry.
AB  - The New Zealand dairy sector relies on robust biosecurity measures to control and
      mitigate a wide range of threats to the industry. To optimize the prioritization
      of organisms and manage the risk they pose to the sector in a transparent and
      credible way, the Dairy Biosecurity Risk Evaluation Framework (D-BRiEF) was
      developed. This comprehensive framework was specifically designed for decision
      support, using a standardized approach to address the full spectrum of
      biosecurity threats to the sector, including exotic and endemic animal disease
      organisms, pest plants and insects. D-BRiEF is underpinned by three main
      processes, namely (i) hazard identification; (ii) multicriteria risk assessment;
      and (iii) communication for risk management. Expert knowledge and empirical data,
      including associated uncertainty, are harnessed in a standardized format. Results
      feed into a probability-impact model that was developed in close collaboration
      with dairy sector economists to provide overall comparative 10-year quantitative
      economic impact estimates for each assessed risk organism. A description of the
      overarching framework, which applies to diverse organism groups, is presented
      with detailed methodology on both endemic and exotic animal disease risk
      organisms. Examples of visual outputs are included, although actual ranking
      results are not reported due to industry confidentiality. D-BRiEF can provide a
      decision advantage to DairyNZ biosecurity risk managers and sector stakeholders
      by creating a transparent process that can be interrogated and updated at
      multiple levels to fully understand the layers of risk posed by different
      organisms.

PMID- 29575644
TI  - HLA-A*02:07 Allele Associates with Clarithromycin-Induced Cutaneous Adverse Drug
      Reactions in Chinese Patients.
AB  - Genetic risk factors could cause cutaneous adverse drug reactions (cADRs) in
      patients after treatment with clarithromycin. This study explored the association
      of HLA class I genes with clarithromycin-cADRs in Han Chinese patients. A total
      of 12 clarithromycin-cADR patients and 34 clarithromycin-tolerant controls were
      recruited for the high-resolution genotyping of HLA class I genes (HLA-A, HLA-B
      and HLA-C). The population controls consisted of 283 Han Chinese retrieved from
      the MHC database for validated comparison. A molecular docking analysis of HLA
      A*02:07 protein and clarithromycin was conducted using glide module with
      Schrodinger Suite. Among all tested HLA alleles, the carrier frequencies of HLA
      A*02:07 (58% versus 5.9%, OR = 22.40, 95% CI = 3.58-139.98, p = 8.20 * 10E-5, pc
      = 1.1 * 10E-3) and HLA-B*46:01 (50% versus 5.9%, OR = 16.00, 95% CI = 2.59-98.99,
      p = 0.002, pc = 0.03) were significantly higher in clarithromycin-cADRs than in
      clarithromycin-tolerant controls. However, when compared to population controls,
      only HLA-A*02:07, and not HLA-B*46:01, reached statistical significance (58%
      versus 15.5%, OR = 7.61, 95% CI = 2.31-25.04, p = 1.2 * 10E-4, pc = 1.7 * 10E-3).
      Furthermore, molecular docking data revealed that clarithromycin could bind to
      and interact with HLA-A*02:07 in two possible binding situations. These data
      suggest that HLA-A*02:07 might be a genetic risk factor for developing
      clarithromycin-cADRs in Han Chinese and serve as a useful biomarker for
      personalized medicine to prevent clarithromycin-cADRs.

PMID- 29575645
TI  - MiR-330-5p negatively regulates ovine preadipocyte differentiation by targeting
      branched-chain aminotransferase 2.
AB  - The differentiation of preadipocytes into adipose tissues is tightly regulated by
      various factors including microRNAs and cytokines. This article aims to study the
      effect of miR-330-5p on expression of BCAT2 in ovine preadipocytes. Ovine
      preadipocytes were isolated, and we found that the miR-330-5p expression
      decreased gradually during the early differentiation of ovine preadipocytes,
      while BCAT2 expression increased. BCAT2 was identified as a direct target of miR
      330-5p, ectopic expression of miR-330-5p could change the expression of both
      BCAT2 mRNA and protein. Silencing BCAT2 had the same inhibition effects as
      overexpressing miR-330-5p on the preadipocyte differentiation, but overexpressing
      BCAT2 had the converse effects. Taken together, we demonstrated that miR-330-5p
      is a negative regulator of differentiation by targeting BCAT2, and clarified the
      role of BCAT2 and miR-330-5p during preadipocyte differentiation.

PMID- 29575646
TI  - Parental body mass index and blood pressure are associated with higher body mass
      index and blood pressure in their adult offspring: a cross-sectional study in a
      resource-limited setting in northern Peru.
AB  - OBJECTIVES: High body mass index (BMI) and blood pressure (BP) are major
      contributors to the high burden of non-communicable diseases in adulthood.
      Individual high-risk and population approaches for prevention require newer
      strategies to target these risk factors and focusing on the family to introduce
      prevention initiatives appears as a promising scenario. Characterisation of the
      relationship between BMI and BP among the adult members of a given family merits
      evaluation. We conducted a secondary analysis of an implementation study in
      Tumbes, Peru, benefiting from data derived from families with at least one adult
      offspring. METHODS: The exposures of interest were the BMI, systolic BP (SBP) and
      diastolic BP (DBP) of the mother and father. The outcomes were the BMI, SBP and
      DBP of the offspring. Mixed-effects linear regression models were conducted.
      RESULTS: The mean age of the offspring, mothers and fathers was 29 (SD: 9.5), 54
      (SD: 11.8) and 59 (SD: 11.6) years, respectively. Father's BMI was associated
      with a quarter-point increase in offspring BMI, regardless of the sex of the
      offspring. Mother's BMI had a similar effect on the BMI of her sons, but had no
      significant effect on her daughters'. Mother's SBP was associated with almost one
      tenth of mmHg increase in the SBP of the adult offspring. There was no evidence
      of an association for DBP. CONCLUSIONS: In families with adult members, the
      higher the parents' BMI and SBP, the higher their adult offspring's levels will
      be.

PMID- 29575647
TI  - The influence of insurance type on stage at presentation, treatment, and survival
      between Asian American and non-Hispanic White lung cancer patients.
AB  - The effect of insurance type on lung cancer diagnosis, treatment, and survival in
      Asian patients living in the United States is still under debate. We have
      analyzed this issue using the Surveillance, Epidemiology, and End Results
      database. There were 102,733 lung cancer patients age 18-64 years diagnosed
      between 2007 and 2013. Multilevel regression analysis was performed to identify
      the association between insurance types, stage at diagnosis, treatment
      modalities, and overall mortality in Asian and non-Hispanic White (NHW) patients.
      Clinical characteristics were significantly different between Asian and NHW
      patients, except for gender. Asian patients were more likely to present with
      advanced disease than NHW patients (ORadj  = 1.12, 95% CI = 1.06-1.19). Asian
      patients with non-Medicaid insurance underwent lobectomy more than NHW patients
      with Medicaid or uninsured; were more likely to undergo mediastinal lymph node
      evaluation (MLNE) (ORadj  = 1.98, 95% CI = 1.72-2.28) and cancer-directed surgery
      and/or radiation therapy (ORadj  = 1.41, 95% CI = 1.20-1.65). Asian patients with
      non-Medicaid insurance had the best overall survival. Uninsured or Medicaid
      covered Asian patients were more likely to be diagnosed with advanced disease,
      less likely to undergo MLNE and cancer-directed treatments, and had shorter
      overall survival than their NHW counterpart.

PMID- 29575649
TI  - Detection and pharmacokinetics of grapiprant following oral administration to
      exercised Thoroughbred horses.
AB  - Traditional therapeutic options for the treatment of lameness associated with
      inflammation in performance horses include administration of cyclooxygenase
      enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use
      of these drugs can adversely impact the health of the horse, anti-inflammatories
      with a more favorable safety profile are warranted. Grapiprant is a newly
      approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and
      safety in other species and which may be a valuable alternative to traditional
      NSAIDs used in the horse. The objectives of the current study were to describe
      drug concentrations and the pharmacokinetics of grapiprant in exercised
      Thoroughbred horses and to develop an analytical method that could be used to
      regulate its use in performance horses. To that end, grapiprant, at a dose of 2
      mg/kg was administered orally to 12 exercised Thoroughbred horses. Blood and
      urine samples were collected prior to and for up to 96 hours post drug
      administration. Drug concentrations were measured using liquid chromatography
      tandem mass spectrometry. Grapiprant remained above the LOQ of the assay (0.005
      ng/mL) in serum for 72 hours post administration and urine concentrations were
      above the LOQ until 96 hours. The Cmax , Tmax and elimination half-life were 31.9
      +/- 13.9 ng/mL, 1.5 +/- 0.5 hours and 5.86 +/- 2.46 hours, respectively. The drug
      was well tolerated in all horses at a dose of 2 mg/kg. Results support further
      study of this compound in horses. Furthermore, development of a highly sensitive
      analytical method demonstrate that this compound can be adequately regulated in
      performance horses.

PMID- 29575648
TI  - Spontaneous development of intratumoral heterogeneity in a transposon-induced
      mouse model of glioma.
AB  - Glioma is the most common form of malignant brain cancer in adults. The Sleeping
      Beauty (SB) transposon-based glioma mouse model allows for effective in vivo
      analysis of candidate genes. In the present study, we developed a transposon
      vector that encodes the triple combination of platelet-derived growth factor
      subunit A (PDGFA), and shRNAs against Nf1 and Trp53 (shNf1/shp53). Initiation and
      progression of glioma in the brain were monitored by expression of a fluorescent
      protein. Transduction of the vector into neural progenitor and stem cells (NPC)
      in the subventricular zone (SVZ) of the neonatal brain induced proliferation of
      oligodendrocyte precursor cells, and promoted formation of highly penetrant
      malignant gliomas within 2-4 months. Cells isolated from the tumors were capable
      of forming secondary tumors. Two transposon vectors, encoding either PDGFA or
      shNf1/shp53 were co-electroporated into NPC. Cells expressing PDGFA or
      shNf1/shp53 were labeled with unique fluorescent proteins allowing visualization
      of the spatial distribution of cells with different genetic alterations within
      the same tumor. Tumor cells located at the center of tumors expressed PDGFA at
      higher levels than those located at the periphery, indicating that intratumoral
      heterogeneity in PDGFA expression levels spontaneously developed within the same
      tumor. Tumor cells comprising the palisading necrosis strongly expressed PDGFA,
      suggesting that PDGFA signaling is involved in hypoxic responses in glioma. The
      transposon vectors developed are compatible with any genetically engineered mouse
      model, providing a useful tool for the functional analysis of candidate genes in
      glioma.

PMID- 29575650
TI  - Efficient allelic replacement in rice by gene editing: A case study of the
      NRT1.1B gene.
AB  - Precise replacement of an existing allele in commercial cultivars with an elite
      allele is a major goal in crop breeding. A single nucleotide polymorphism in the
      NRT1.1B gene between japonica and indica rice is responsible for the improved
      nitrogen use efficiency in indica rice. Herein, we precisely replaced the
      japonica NRT1.1B allele with the indica allele, in just one generation, using
      CRISPR/Cas9 gene-editing technology. No additional selective pressure was needed
      to enrich the precise replacement events. This work demonstrates the feasibility
      of replacing any genes with elite alleles within one generation, greatly
      expanding our ability to improve agriculturally important traits.

PMID- 29575651
TI  - C-reactive protein is an independent prognostic marker in patients with tongue
      carcinoma - A retrospective study.
AB  - OBJECTIVES: Reliable prognostic markers are lacking for tongue carcinoma. C
      reactive protein (CRP) and a ratio from neutrophils/lymphocytes (NLR) are
      biomarkers, associated with prognosis in solid cancers. Aim of this work was to
      investigate the role of CRP and NLR in prognosis of patients with tongue
      carcinoma. DESIGN: Retrospective cohort study. SETTING: We retrospectively
      analysed data of patients treated for tongue carcinoma at our institution. Levels
      of CRP, Neutrophils and Lymphocytes were measured pretherapeutic. PARTICIPANTS:
      197 patients treated for squamous cell carcinoma of the tongue between 2002 and
      2015. MAIN OUTCOME MEASURES: Overall survival, disease-free survival. RESULTS:
      Elevated CRP was significantly associated with shorter overall survival in our
      cohort in uni- and multivariate analysis. NLR was not associated with prognosis.
      CONCLUSION: In the present study we could confirm the role of CRP as an
      independent prognostic marker in patients with tongue carcinoma. Incorporating
      this marker in prognostication could represent a valuable and moreover
      inexpensive tool for improved decisions making concerning therapy in the future.

PMID- 29575652
TI  - Noninvasive evaluation of cerebrospinal fluid pressure in ocular hypertension: a
      preliminary study.
AB  - PURPOSE: To compare the orbital cerebral spinal fluid pressure (CSFP) and trans
      lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular
      hypertensive (OH) subjects and controls. METHODS: Cross-sectional observational
      study. Magnetic resonance imaging was used to measure orbital subarachnoid space
      width (OSASW). The CSFP (mm Hg) was estimated from a published formula as 17.54 *
      MRI derived OSASW at 15 mm behind the globe + 0.47 * body mass index + 0.13 *
      mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP.
      RESULTS: The orbital subarachnoid space width was significantly wider (p = 0.01)
      in the OH group than in the control group at all three measurement locations. The
      MRI derived CSFP value in OH (14.9 +/- 2.9 mm Hg) was significantly higher than
      in the normal group (12.0 +/- 2.8 mm Hg; p < 0.01). The estimated TLCPD value in
      OH (9.0 +/- 4.2 mm Hg) was significantly higher than in controls (3.6 +/- 3.0 mm
      Hg; p < 0.01). CONCLUSION: The wider OSASW and higher estimated CSFP in OH
      subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could
      be protective, the higher TLCPD in OH may play a significant role in the risk of
      developing glaucoma.

PMID- 29575653
TI  - Transition-Metal-Based Electrocatalysts as Cocatalysts for Photoelectrochemical
      Water Splitting: A Mini Review.
AB  - Converting solar energy into hydrogen via photoelectrochemical (PEC) water
      splitting is one of the most promising approaches for a sustainable energy
      supply. Highly active, cost-effective, and robust photoelectrodes are undoubtedly
      crucial for the PEC technology. To achieve this goal, transition-metal-based
      electrocatalysts have been widely used as cocatalysts to improve the performance
      of PEC cells for water splitting. Herein, this Review summarizes the recent
      progresses of the design, synthesis, and application of transition-metal-based
      electrocatalysts as cocatalysts for PEC water splitting. Mo, Ni, Co-based
      electrocatalysts for the hydrogen evolution reaction (HER) and Co, Ni, Fe-based
      electrocatalysts for the oxygen evolution reaction (OER) are emphasized as
      cocatalysts for efficient PEC HER and OER, respectively. Particularly, some most
      efficient and robust photoelectrode systems with record photocurrent density or
      durability for the half reactions of HER and OER are highlighted and discussed.
      In addition, the self-biased PEC devices with high solar-to-hydrogen efficiency
      based on earth-abundant materials are also addressed. Finally, this Review is
      concluded with a summary and remarks on some challenges and opportunities for the
      further development of transition-metal-based electrocatalysts as cocatalysts for
      PEC water splitting.

PMID- 29575654
TI  - Spermidine promotes nucleus pulposus autophagy as a protective mechanism against
      apoptosis and ameliorates disc degeneration.
AB  - Spermidine has therapeutic effects in many diseases including as heart diastolic
      function, myopathic defects and neurodegenerative disorders via autophagy
      activation. Autophagy has been found to mitigate cell apoptosis in intervertebral
      disc degeneration (IDD). Accordingly, we theorize that spermidine may have
      beneficial effects on IDD via autophagy stimulation. In this study, spermidine's
      effect on IDD was evaluated in tert-butyl hydroperoxide (TBHP)-treated nucleus
      pulposus cells of SD rats in vitro as well as in a puncture-induced rat IDD
      model. We found that autophagy was actuated by spermidine in nucleus pulposus
      cells. In addition, spermidine treatment weakened the apoptotic effects of TBHP
      in nucleus pulposus cells. Spermidine increased the expression of anabolic
      proteins including Collagen-II and aggrecan and decreased the expression of
      catabolic proteins including MMP13 and Adamts-5. Additionally, autophagy blockade
      using 3-MA reversed the beneficial impact of spermidine against nucleus pulposus
      cell apoptosis. Autophagy was thus important for spermidine's therapeutic effect
      on IDD. Spermidine-treated rats had an accentuated T2-weighted signal and a
      diminished histological degenerative grade than vehicle-treated rats, showing
      that spermidine inhibited intervertebral disc degeneration in vivo. Thus,
      spermidine protects nucleus pulposus cells against apoptosis through autophagy
      activation and improves disc, which may be beneficial for the treatment of IDD.

PMID- 29575655
TI  - Potential implications of a more timely living kidney donor evaluation.
AB  - Living donor kidney transplantation is the most promising way to avoid or
      minimize the amount of time a recipient spends on dialysis before
      transplantation. We studied 887 living kidney donors at 5 transplant centers in
      Ontario, Canada, who started their evaluation and donated between April 2006 and
      March 2014. Using a series of hypothetical scenarios, we estimated the impact of
      an earlier living donor evaluation completion and donation on the number pre
      emptive transplants, the time spent on dialysis, healthcare cost savings from
      averted dialysis costs (CAD $2016), and the number of additional transplants.
      During the study period, if the donor transplants occurred 3 months earlier, the
      healthcare system would save on average $12 055 (standard deviation [SD] $13 594)
      per recipient; 21 recipients could have avoided dialysis altogether, and 57
      additional transplants (a 26% increase) could have occurred each year. For the
      220 living kidney donor transplants performed in Ontario, Canada, each year, this
      translates to a total annual cost savings of $2.7M. In conclusion, a more timely
      evaluation of living donor candidates and their intended recipients may increase
      the supply of kidneys for transplantation. Improved evaluation efficiency may
      also yield more pre-emptive transplants and substantial healthcare cost savings
      through averted dialysis costs.

PMID- 29575656
TI  - Comparison of Power, Prognosis, and Extrapolation Properties of Four Population
      Pharmacodynamic Models of HbA1c for Type 2 Diabetes.
AB  - Reusing published models saves time; time to be used for informing decisions in
      drug development. In antihyperglycemic drug development, several published HbA1c
      models are available but selecting the appropriate model for a particular purpose
      is challenging. This study aims at helping selection by investigating four HbA1c
      models, specifically the ability to identify drug effects (shape, site of action,
      and power) and simulation properties. All models could identify glucose effect
      nonlinearities, although for detecting the site of action, a mechanistic glucose
      model was needed. Power was highest for models using mean plasma glucose to drive
      HbA1c formation. Insulin contribution to power varied greatly depending on the
      drug target; it was beneficial only if the drug target was insulin secretion. All
      investigated models showed good simulation properties. However, extrapolation
      with the mechanistic model beyond 12 weeks resulted in drug effect
      overprediction. This investigation aids drug development in decisions regarding
      model choice if reusing published HbA1c models.

PMID- 29575657
TI  - Consensus on procedures to include in a simulation-based curriculum in
      ophthalmology: a national Delphi study.
AB  - PURPOSE: The number of available simulation-based models for technical skills
      training in ophthalmology is rapidly increasing, and development of training
      programmes around these procedures should follow a structured approach. The aim
      of this study was to identify all technical procedures that should be integrated
      in a simulation-based curriculum in ophthalmology. METHODS: Key opinion leaders
      involved in the education of ophthalmologists in Denmark including heads of
      departments, heads of clinical education, professors and board members of the
      society were invited to participate in a three-round Delphi process. Round 1
      aimed at identifying technical procedures that physicians should be able to
      perform competently when completing specialty training; round 2 involved
      characterization of each procedure including frequency, number of operators, risk
      and/or discomfort for patients associated with an inexperienced physician, and
      feasibility of simulation-based training; round 3 included a priority ranking of
      procedures. RESULTS: The response rate for each round was 71%, 64% and 64%,
      respectively. Sixty-five procedures were reduced to 25 prioritized procedures
      during the three rounds. Two-thirds of the procedures that were identified and
      highly prioritized were therapeutic procedures such as intravitreal injection
      therapy, yttrium-aluminium-garnet laser iridotomy/capsulotomy, minor ocular
      surface procedures and retinal argon laser therapy. The diagnostic procedures
      that were prioritized were ocular ultrasound, superficial keratectomy and optical
      coherence tomography (OCT). CONCLUSION: The Delphi process identified and
      prioritized 25 procedures that should be practised in a simulation-based
      environment to achieve competency before working with patients. The list may be
      used to guide the development of future training programmes for ophthalmologists.

PMID- 29575658
TI  - Metabolic traits predict the effects of warming on phytoplankton competition.
AB  - Understanding how changes in temperature affect interspecific competition is
      critical for predicting changes in ecological communities with global warming.
      Here, we develop a theoretical model that links interspecific differences in the
      temperature dependence of resource acquisition and growth to the outcome of
      pairwise competition in phytoplankton. We parameterised our model with these
      metabolic traits derived from six species of freshwater phytoplankton and tested
      its ability to predict the outcome of competition in all pairwise combinations of
      the species in a factorial experiment, manipulating temperature and nutrient
      availability. The model correctly predicted the outcome of competition in 72% of
      the pairwise experiments, with competitive advantage determined by difference in
      thermal sensitivity of growth rates of the two species. These results demonstrate
      that metabolic traits play a key role in determining how changes in temperature
      influence interspecific competition and lay the foundation for mechanistically
      predicting the effects of warming in complex, multi-species communities.

PMID- 29575659
TI  - Is routine histological tissue sampling during endoscopic dacryocystorhinostomy
      advantageous? A retrospective analysis of 213 patients.

PMID- 29575660
TI  - Subthreshold social cognitive deficits may be a key to distinguish 22q11.2DS from
      schizophrenia.
AB  - AIM: Social cognitive impairments are core features in 22q11.2 deletion syndrome
      (22q11.2DS) and schizophrenia (SCZ). Indeed, adults with 22q.11.2 DS often have
      poorer social competence as well as poorer performance on measures of social
      cognitive skills (emotion recognition and theory of mind, ToM) compared with
      typically developing people. However, studies comparing specific social cognitive
      components in 22q11.2DS and SCZ have not yet been widely conducted. METHODS: In
      this study we compared performances of 22q11.2DS and SCZ on both facial emotion
      recognition and ToM. Patients with 22q11.2DS (n = 18) and matched SCZ patients
      were recruited. After neuropsychological testing, the facial emotion recognition
      test assessed the patients' ability to recognize six basic, universal emotions
      (joy, anger, sadness, fear, disgust, and contempt). The Versailles-situational
      intentional reading evaluated ToM with six scenes from movies showing characters
      in complex interactions (involving hints, lies, and indirect speech). RESULTS: We
      show that 22q11.2DS exhibited significantly lower performance in emotion
      recognition than SCZ patients did, especially for disgust, contempt, and fear.
      This impairment seems to be a core cognitive phenotype in 22q11.2DS, regardless
      of the presence of SCZ symptoms. Concerning ToM, our results may highlight the
      same impairment level in 22q11.2DS and SCZ but require to be replicated in a
      larger cohort. CONCLUSION: Our results document the existence of threshold social
      cognitive deficits distinguishing 22q11.2DS from SCZ.

PMID- 29575661
TI  - Early diagnosis of infection occurs in burned patients and verification in vitro.
AB  - OBJECTIVE: To explore the trend of CD64+ neutrophils being present in the
      peripheral blood of patients with burns and verification in vitro. METHOD: We
      isolated and purified CD64+ neutrophils from healthy people, stimulated cells
      with inactivated Staphylococcus aureus in vitro to make them proliferate and
      analyzed them with Modfit 2 analysis software. Patients with burns were divided
      into two groups, depending on whether there was a complicated infection or not,
      and 35 healthy participants were enrolled as blank group. WBC and CD64+
      neutrophil counts were detected and then analyzed the specificity and sensitivity
      according to the ROC curve. RESULTS: The proliferation index of the CD64+ cells
      in the experimental wells was significantly higher than that in the control wells
      (P < .05). The CD64+ cell counts in the peripheral blood of patients in the
      infection group were significantly higher than patients without infection, but
      also higher than the healthy people (P < .05). The sensitivity and specificity of
      CD64+ cellular diagnosis for burn infection were 94.2% and 76.8%, respectively,
      according to the ROC curve, which were significantly better than those of the
      WBCs. CONCLUSION: CD64+ cells in the peripheral blood of patients with burns
      complicated by infection increased significantly, and thus, it can be regarded as
      an early diagnostic indicator of burns with a concurrent infection.

PMID- 29575662
TI  - Formality in workplace-based assessments.

PMID- 29575663
TI  - Exploring simulation in medical clerkships.

PMID- 29575664
TI  - Taking qualitative research to the next level.

PMID- 29575665
TI  - Embracing error.

PMID- 29575666
TI  - Becoming 'ward smart' medical students: a response.

PMID- 29575667
TI  - How to...write a good research question.
AB  - This paper, on writing research questions, is the first in a series that aims to
      support novice researchers within clinical education, particularly those
      undertaking their first qualitative study. Put simply, a research question is a
      question that a research project sets out to answer. Most research questions will
      lead to a project that aims to generate new insights, but the target audience and
      the methodology will vary widely. The term 'evaluation question' is used less
      commonly, but the same principles apply. The key difference is that evaluation
      questions are typically more focused on the immediate context: for example, the
      effectiveness of an educational intervention in a particular setting. Whether
      your ambition is for research or evaluation, we hope that you will find this
      paper helpful for designing your own educational projects. A research question is
      a question that a research project sets out to answer.

PMID- 29575668
TI  - Early management of patients with medication-overuse headache: results from a
      multicentre clinical study.
AB  - BACKGROUND AND PURPOSE: Educational intervention has proved to be effective in
      reducing drug abuse in uncomplicated medication-overuse headache (MOH). This
      ancillary of the SAMOHA multicentre study aimed to assess any differences in
      phenotypic characteristics, type and amount of drugs overused, and comorbidities
      between patients with MOH who responded to simple advice and those who did not.
      METHODS: Demographic and clinical headache data of the last 3 months before
      enrollment of patients were collected and patients were then asked to fill out a
      daily headache diary for 4 weeks. Patients were then divided into two subgroups,
      i.e. those with confirmed MOH continued in the study [randomized (R) group],
      whereas those who did not still show any features of MOH dropped out of the
      study. RESULTS: A total of 88 (67.7%) patients still met the inclusion criteria
      after the baseline 4 weeks (R group). Conversely, 42 (32.3%) patients dropped out
      of the study. A detailed analysis of those who dropped out revealed that only 34
      were not randomized at visit 2 because they no longer satisfied the inclusion
      criteria for MOH [screening failures (SF) group]. The SF group was significantly
      younger and had fewer years of migraine history than the R group. Moreover, the
      SF group had a significantly shorter history of chronicity compared with the R
      group. CONCLUSIONS: Our findings suggest that in MOH trials, after an educational
      session, an observational period is needed in order to confirm the diagnosis of
      MOH and to avoid overestimation of the effect of other treatments used to manage
      MOH. Future research should focus mainly on those patients with MOH who do not
      respond to simple advice and with unsuccessful withdrawal.

PMID- 29575669
TI  - Comparison of a prepCheck-supported self-assessment concept with conventional
      faculty supervision in a pre-clinical simulation environment.
AB  - OBJECTIVES: This study aimed to evaluate the educational outcome of a digitally
      based self-assessment concept (prepCheck; DentsplySirona, Wals, Austria) for pre
      clinical undergraduates in the context of a regular phantom-laboratory course.
      MATERIALS AND METHODS: A sample of 47 third-year dental students participated in
      the course. Students were randomly divided into a prepCheck-supervised (self
      assessment) intervention group (IG; n = 24); conventionally supervised students
      constituted the control group (CG; n = 23). During the preparation of three
      surface (MOD) class II amalgam cavities, each IG participant could analyse a
      superimposed 3D image of his/her preparation against the "master preparation"
      using the prepCheck software. In the CG, several course instructors performed the
      evaluations according to pre-defined assessment criteria. After completing the
      course, a mandatory (blinded) practical examination was taken by all course
      participants (both IG and CG students), and this assessment involved the
      preparation of a MOD amalgam cavity. Then, optical impressions by means of a
      CEREC-Omnicam were taken to digitalize all examination preparations, followed by
      surveying and assessing the latter using prepCheck. RESULTS: The statistical
      analysis of the digitalized samples (Mann-Whitney U test) revealed no significant
      differences between the cavity dimensions achieved in the IG and CG (P = .406).
      Additionally, the sum score of the degree of conformity with the "master
      preparation" (maximum permissible 10% of plus or minus deviation) was comparable
      in both groups (P = .259). CONCLUSION: The implemented interactive digitally
      based, self-assessment learning tool for undergraduates appears to be equivalent
      to the conventional form of supervision. Therefore, such digital learning tools
      could significantly address the ever-increasing student to faculty ratio.

PMID- 29575670
TI  - Special Issue: Cheminformatics in Drug Discovery.
AB  - Digital Drug Discovery: Guest Editors Andreas Bender (University of Cambridge)
      and Nathan Brown (BenevolentAI) present the 20 articles included in this Special
      Issue on Cheminformatics in Drug Design. As they summarize each article, they
      also discuss the common themes within in silico drug discovery that these papers
      represent.

PMID- 29575671
TI  - Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis
      Patients Through Declining Exosomal MicroRNA-155.
AB  - OBJECTIVE: Several studies have shown that rituximab may enhance hepatitis C
      virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the
      host immune response in HCV infection; miRNAs can be packaged into the exosomes
      and then shuttled by the exosomes to aid biologic functions. However, the role of
      exosomal miRNAs (exo-miRNAs) in rituximab-related HCV activity enhancement
      remains unclear. METHODS: The association between rituximab and increased HCV
      activity was examined using an in vitro cell-based assay. Purified exosomes were
      confirmed using immunoblotting and flow cytometry and quantified using enzyme
      linked immunosorbent assay. Exosomal miRNA-155 (exo-miR-155) levels were measured
      using quantitative reverse transcription-polymerase chain reaction. RESULTS: In
      vitro data showed that B cell-derived miR-155 could inhibit HCV replication in
      hepatocytes through exosome transmission. Rituximab could both induce B cell
      depletion and affect intracellular miR-155 production as well as exo-miR-155
      transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum
      exosome levels were increased in rheumatoid arthritis (RA) patients with HCV
      infection compared with the levels in RA patients without HCV infection (P <
      0.01). The exo-miR-155 levels were significantly increased in RA patients with
      HCV infection compared with those without infection (P < 0.01). A significantly
      greater decrement of exo-miR-155 expression was observed after rituximab therapy
      compared with those observed before therapy (P < 0.01), and hepatitis C viral
      loads increased simultaneously (P < 0.05). CONCLUSION: Circulating exo-miR-155
      levels were negatively correlated with hepatitis C viral loads and subsequently
      associated with rituximab-related HCV activity enhancement in RA patients. Exo
      miR-155 may become a potential diagnostic biomarker or therapeutic target.

PMID- 29575672
TI  - Serological evidence of widespread exposure of Grenada fruit bats to chikungunya
      virus.
AB  - Antibody detection against selected potentially zoonotic vector-borne
      alphaviruses and flaviviruses was conducted on sera from bats from all six
      parishes in Grenada, West Indies. Sera were tested for (i) antibodies to
      flaviviruses West Nile virus, St. Louis encephalitis virus, Ilheus virus,
      Bussuquara virus (BSQV), Rio Bravo virus and all four serotypes of dengue virus
      (DENV) by plaque reduction neutralization test (PRNT); (ii) antibodies to
      alphaviruses western equine encephalitis virus, Venezuelan equine encephalitis
      virus and eastern equine encephalitis virus by epitope-blocking enzyme-linked
      immunosorbent assay (ELISA); and (iii) antibodies to the alphavirus chikungunya
      (CHIKV) by PRNT. Two species of fruit bats were sampled, Artibeus jamaicensis and
      Artibeus lituratus, all roosting in or within 1,000 m of human settlements.
      Fifteen (36%) of the 42 bats tested for neutralizing antibodies to CHIKV were
      positive. The CHIKV-seropositive bats lived in localities spanning five of the
      six parishes. All 43 bats tested for epitope-blocking ELISA antibody to the other
      alphaviruses were negative, except one positive for Venezuelan equine
      encephalitis virus. All 50 bats tested for neutralizing antibody to flaviviruses
      were negative, except one that had a BSQV PRNT80 titre of 20. The CHIKV serology
      results indicate that bats living close to and within human settlements were
      exposed to CHIKV in multiple locations. Importantly, bats for this study were
      trapped a year after the introduction and peak of the human CHIKV epidemic in
      Grenada. Thus, our data indicate that bats were exposed to CHIKV possibly during
      a time of marked decline in human cases.

PMID- 29575673
TI  - Determining One-Year Trajectories of Low-Back-Related Leg Pain in Primary Care
      Patients: Growth Mixture Modeling of a Prospective Cohort Study.
AB  - OBJECTIVE: The clinical presentation and outcome of patients with back and leg
      pain in primary care are heterogeneous and may be better understood by
      identification of homogeneous and clinically meaningful subgroups. Subgroups of
      patients with different back pain trajectories have been identified, but little
      is known about the trajectories for patients with back-related leg pain. This
      study sought to identify distinct leg pain trajectories, and baseline
      characteristics associated with membership of each group, in primary care
      patients. METHODS: Monthly data on leg pain intensity were collected over 12
      months for 609 patients participating in a prospective cohort study of adult
      patients seeking health care for low-back and leg pain, including sciatica, of
      any duration and severity, from their general practitioner. Growth mixture
      modeling was used to identify clusters of patients with distinct leg pain
      trajectories. Trajectories were characterized using baseline demographic and
      clinical examination data. Multinomial logistic regression was used to predict
      latent class membership, with a range of covariates. RESULTS: Four patient
      clusters were identified: improving mild pain (58%), persistent moderate pain
      (26%), persistent severe pain (13%), and improving severe pain (3%). Clusters
      showed statistically significant differences in a number of baseline
      characteristics. CONCLUSION: Four trajectories of leg pain were identified.
      Clusters 1, 2, and 3 were generally comparable to back pain trajectories, while
      cluster 4, with major improvement in pain, is infrequently identified. Awareness
      of such distinct patient groups improves understanding of the course of leg pain
      and may provide a basis of classification for intervention.

PMID- 29575674
TI  - Dentin dysplasia type I-A dental disease with genetic heterogeneity.
AB  - Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin
      dysplasia (DD), which are autosomal dominant diseases characterized by altered
      dentin structure such as abnormality in dentin mineralization and the absence of
      root dentin. Shields classified DGI into three subgroups and DD into two
      subtypes. Although they are all hereditary dentin diseases, they do not share the
      same causative genes. To date, the pathogenic genes of DGI type I, which is
      considered a clinical manifestation of syndrome osteogenesis imperfecta, include
      COL1A1 and COL1A2. Mutations of the DSPP gene, which encodes the dentin
      sialophosphoprotein, a major non-collagenous protein, are responsible for three
      isolated dentinal diseases: DGI-II, DGI-III, and DD-II. However, DD-I appears to
      be special in that researchers have found three pathogenicity genes-VPS4B, SSUH2,
      and SMOC2-in three affected families from different countries. It is believed
      that DD-I is a genetically heterogeneous disease and is distinguished from other
      types of dentin disorders. This review summarizes the DD-I literature in the
      context of clinical appearances, radiographic characteristics, and functions of
      its pathogenic genes and aims to serve clinicians in further understanding and
      diagnosing this disease.

PMID- 29575675
TI  - Novel oral anticoagulant use in adult Fontan patients: A single center
      experience.
AB  - OBJECTIVE: Adult Fontan patients are at increased risk for thrombosis and
      thromboembolic complications leading to increased morbidity and mortality. Most
      are prescribed antiplatelet or anticoagulant therapy for thromboprophylaxis;
      novel oral anticoagulants (NOACs) are uncommonly used given lack of data on their
      use in this population and generalized concerns regarding Fontan patients'
      abnormal coagulation. We report the largest single-center experience with the use
      of NOACs for treatment and prophylaxis of thrombosis and thromboembolism in adult
      Fontan patients. RESULTS: A retrospective chart review identified 21 patients (11
      female, 10 male), median age 33 years (18-50) at first initiation, who were
      prescribed a NOAC on 27 different occasions. The main indications for
      anticoagulation were arrhythmia (N = 12), thrombosis (N = 8), and persistent
      right to left shunts (N = 2); one patient was initially on anticoagulation for
      arrhythmia but restarted for thrombosis. The most common indications for
      initiation of a NOAC over warfarin were patient/provider preference (N = 11),
      labile international normalized ratio (INR) (N = 5), initiation of therapy
      elsewhere (N = 3), and history of poor clinical follow-up (N = 2). Over a
      cumulative 316 months of patient therapy, one new thrombotic event was noted. No
      major or nonmajor bleeding events occurred, and 10 patients experienced minor
      bleeding that did not require the cessation of therapy. One patient died from
      multiorgan system failure following an unwitnessed, out of hospital arrest. At
      present, 10 patients remain on NOAC therapy in the setting of ongoing arrhythmia
      (N = 4), history of stroke (N = 2), history of pulmonary embolism (N = 2),
      history of deep vein thrombosis (N = 1), and history of right ventricle thrombus
      (N = 1). CONCLUSIONS: While our study is limited by size, our results suggest
      that NOACs may be a non-inferior alternative to traditional anticoagulation and
      that further study is warranted.

PMID- 29575676
TI  - Ocular microcirculation measurement with laser speckle flowgraphy and optical
      coherence tomography angiography in glaucoma.
AB  - PURPOSE: To compare glaucoma severity with ocular microcirculation, measured with
      either laser speckle flowgraphy (LSFG) or optical coherence tomography
      angiography (OCTA). METHODS: We retrospectively studied 82 eyes of 82 open-angle
      glaucoma (OAG) patients who underwent same-day LSFG and OCTA examinations, with
      20 eyes of 20 healthy subjects as controls. In OCTA images, vessel density (VD)
      (%) was calculated in concentric regions (regions 1, 2 and 3: R1, R2 and R3,
      respectively) defined by 1.6-, 3.2- and 3.6-mm-diameter circles around the optic
      nerve head (ONH). In R3, the large vessels were automatically masked to calculate
      pure capillary density (auto R3 VD). LSFG-measured mean blur rate (MBR) was
      examined in the overall ONH (MA), vessel-area ONH (MV) and tissue-area ONH (MT).
      RESULTS: Auto R3 VD had high reproducibility (coefficient of variation: 1.65
      3.88%) and accurately reflected manual R3 VD [mean bias: -0.0087% (auto R3 VD -
      manual R3 VD)]. MA and MT decreased significantly with OAG severity, especially
      in the early OAG stages (control vs. mild: p = 0.003 and p < 0.001,
      respectively). R1 VD did not change with severity. R2 and auto R3 VD decreased
      significantly with OAG severity, especially in the severe stages (R2, mild vs.
      severe: p = 0.008; auto R3 VD, mild vs. severe: p < 0.001, moderate vs. severe: p
      = 0.028). CONCLUSION: Optical coherence tomography angiography-derived auto R3 VD
      is novel, reproducible and accurately reflects manual measurements. It is useful
      for differentiating moderate and advanced glaucoma, while LSFG-derived MT is
      useful for identifying early glaucoma.

PMID- 29575677
TI  - Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and
      Migration of T98G Human Glioblastoma Cells.
AB  - The active form of vitamin D (1alpha,25-dihydroxyvitamin D) acts as a steroid
      hormone and binds to the vitamin D receptor. This receptor is expressed in most
      cell types including cells in the central nervous system (CNS). Vitamin D has
      several functions in the body including effects on brain development,
      neuroprotection and immunological regulation. It has been shown that vitamin D
      has antiproliferative activities in different cancer cell lines. Tacalcitol and
      calcipotriol are synthetic analogues of 1alpha,25-dihydroxyvitamin D with reduced
      effect on calcium metabolism. The aim of this study was to analyse the effects of
      tacalcitol and calcipotriol on cell viability, proliferation and migration in the
      human glioblastoma cell line T98G. Glioblastoma is the most lethal type of
      primary tumours in the CNS. Both analogues decreased cell viability and/or
      growth, dose-dependently, in concentrations between 1 nM and 10 MUM. Manual
      counting indicated suppressive effects by the vitamin D analogues on
      proliferation. Treatment with tacalcitol strongly suppressed thymidine
      incorporation, indicating that the vitamin D analogues mainly inhibit
      proliferation. Also, effects on cell migration were measured with wound-healing
      assay. Both calcipotriol and tacalcitol reduced the migration rate of T98G cells
      compared to vehicle-treated cells. However, they had no effect on caspase-3 and 
      7 activities, suggesting that their mechanism of action does not involve
      induction of apoptosis. The current results indicate that the vitamin D analogues
      tacalcitol and calcipotriol strongly reduce proliferation and migration of human
      glioblastoma T98G cells, suggesting a potential role for this type of compounds
      in treatment of brain cancer.

PMID- 29575678
TI  - Impact of percutaneous femoral arteriotomy closure using the MANTATM device on
      vascular and bleeding complications after transcatheter aortic valve replacement.
AB  - OBJECTIVES: To evaluate the feasibility of fully percutaneous closure using a
      novel collagen-based vascular closure device after transfemoral aortic valve
      replacement (TAVR). BACKGROUND: TAVR is utilized increasingly for the treatment
      of severe symptomatic aortic stenosis. Vascular complications related to access
      and closure dominate the adverse event profile of the procedure despite
      progressively reducing arteriotomy caliber. The advent of a novel collagen-based
      device (MANTATM ) and preliminary data suggest this could be used as a routine
      percutaneous closure device. METHODS: A prospective observational study of
      unselected consecutive patients undergoing TAVR in a single center. Data were
      collected via hospital electronic records and the SWEDEHEART registry. The
      primary clinical outcome was closure success and time to hemostasis. Secondary
      outcomes included VARC-2 defined major and minor vascular and bleeding
      complications within 30 days using suture-based closure with Prostar-XL within
      the same center. RESULTS: A consecutive cohort of 346 patients underwent TAVR via
      the transfemoral approach. Vascular closure with MANTATM was successful in all
      with a mean time to hemostasis of 42 sec (SD 115.5, range 0-600). The composite
      of all-cause mortality and major complications related to the main access site
      was similar between the groups (1.1% vs 1.9%, P = .61). Major bleeding occurred
      less frequently with MANTA TM (1.1% vs 7.8%, P = .02). CONCLUSION: The novel use
      of a collagen-based vascular closure device for large caliber arteriotomy is
      feasible in an unselected population undergoing transfemoral TAVR and appears
      efficacious compared to percutaneous suture-based closure. These data should
      prompt larger studies to evaluate efficacy and safety.

PMID- 29575679
TI  - Contrasting P acquisition strategies of the bacterial communities associated with
      legume and grass in subtropical orchard soil.
AB  - Phosphorus (P) cycling is a fundamental process driven by microorganisms, and
      plants can regulate P cycling directly or via their influence on the soil
      microbial community. However, the differential P cycling patterns associated with
      legumes and grass are largely unknown. Therefore, we investigated the microbial
      community involved in P cycling in subtropical soil grown with stylo
      (Stylosanthes guianensis, legume) or bahiagrass (Paspalum notatum, grass) using
      metagenomic sequencing. P fractionation indicated that sparingly soluble
      inorganic P (Pi) accounted for approximately 75% of P pool. Bacteria involved in
      sparingly soluble Pi solubilization (pqq, gad, JEN) were more abundant in
      bahiagrass soil, with Candidatus Pelagibacter, Trichodesmium, Neorickettsia,
      Nitrobacter, Paraburkholderia, Candidatus Solibacter, Burkholderia as major
      contributors. In contrast, bacteria involved in organic P (Po) mineralization
      (php, glpQ, phn) were more abundant in stylo soil, consistent with phosphatase
      activity and Frankia, Kyrpidia, Thermobispora, Streptomyces, Rhodococcus were
      major contributors. Bacteria taking up low molecular-weight Po were more abundant
      in stylo soil than in bahiagrass soil, while those taking up Pi were less
      abundant. These data suggest that bacterial communities associated with legumes
      and grass develop contrasting P acquisition strategies, highlighting the
      possibility of intercropping with legumes and grass for better P cycling.

PMID- 29575680
TI  - Salinity tolerances and use of saline environments by freshwater turtles:
      implications of sea level rise.
AB  - The projected rise in global mean sea levels places many freshwater turtle
      species at risk of saltwater intrusion into freshwater habitats. Freshwater
      turtles are disproportionately more threatened than other taxa; thus,
      understanding the role of salinity in determining their contemporary distribution
      and evolution should be a research priority. Freshwater turtles are a slowly
      evolving lineage; however, they can adapt physiologically or behaviourally to
      various levels of salinity and, therefore, temporarily occur in marine or
      brackish environments. Here, we provide the first comprehensive global review on
      freshwater turtle use and tolerance of brackish water ecosystems. We link
      together current knowledge of geographic occurrence, salinity tolerance,
      phylogenetic relationships, and physiological and behavioural mechanisms to
      generate a baseline understanding of the response of freshwater turtles to
      changing saline environments. We also review the potential origins of salinity
      tolerance in freshwater turtles. Finally, we integrate 2100 sea level rise (SLR)
      projections, species distribution maps, literature gathered on brackish water
      use, and a phylogeny to predict the exposure of freshwater turtles to projected
      SLR globally. From our synthesis of published literature and available data, we
      build a framework for spatial and phylogenetic conservation prioritization of
      coastal freshwater turtles. Based on our literature review, 70 species (~30% of
      coastal freshwater turtle species) from 10 of the 11 freshwater turtle families
      have been reported in brackish water ecosystems. Most anecdotal records,
      observations, and descriptions do not imply long-term salinity tolerance among
      freshwater turtles. Rather, experiments show that some species exhibit potential
      for adaptation and plasticity in physiological, behavioural, and life-history
      traits that enable them to endure varying periods (e.g. days or months) and
      levels of saltwater exposure. Species that specialize on brackish water habitats
      are likely to be vulnerable to SLR because of their exclusive coastal
      distributions and adaptations to a narrow range of salinities. Most species,
      however, have not been documented in brackish water habitats but may also be
      highly vulnerable to projected SLR. Our analysis suggests that approximately 90%
      of coastal freshwater turtle species assessed in our study will be affected by a
      1-m increase in global mean SLR by 2100. Most at risk are freshwater turtles
      found in New Guinea, Southeast Asia, Australia, and North and South America that
      may lose more than 10% of their present geographic range. In addition, turtle
      species in the families Chelidae, Emydidae, and Trionychidae may experience the
      greatest exposure to projected SLR in their present geographic ranges. Better
      understanding of survival, growth, reproductive and population-level responses to
      SLR will improve region-specific population viability predictions of freshwater
      turtles that are increasingly exposed to SLR. Integrating phylogenetic,
      physiological, and spatial frameworks to assess the effects of projected SLR may
      improve identification of vulnerable species, guilds, and geographic regions in
      need of conservation prioritization. We conclude that the use of brackish and
      marine environments by freshwater turtles provides clues about the evolutionary
      processes that have prolonged their existence, shaped their unique coastal
      distributions, and may prove useful in predicting their response to a changing
      world.

PMID- 29575681
TI  - Sunflower shadow in the central field of vision.

PMID- 29575682
TI  - Functional outcome and service engagement in major depressive disorder with
      psychotic features: comparisons with schizophrenia, schizoaffective disorder and
      bipolar disorder in a 6-year follow-up of the Cavan-Monaghan First Episode
      Psychosis Study (CAMFEPS).
AB  - OBJECTIVE: While long-term outcome following a first psychotic episode is well
      studied in schizophrenia (SZ), schizoaffective disorder (SA), and bipolar
      disorder (BD), major depressive disorder with psychotic features (MDDP) has
      received less investigation. This study compares MDDP with SZ, SA, and BD at 6
      year follow-up. METHODS: At 6 years after a first psychotic episode, follow-up
      data on psychopathology, functioning, quality of life, and service engagement
      were obtained for 27 cases of MDDP in comparison to 60 SZ, 27 SA, and 35 BD.
      RESULTS: Positive psychotic symptoms were less prominent in MDDP and BD than in
      SZ and SA. Negative symptoms, impaired functioning, and reduction in objectively
      determined quality of life were less prominent in MDDP and BD, intermediate in SA
      and most prominent in SZ. However, subjectively determined quality of life was
      indistinguishable across diagnoses. Service engagement was highest for MDDP,
      intermediate for SA and BD, and lowest for SZ. CONCLUSIONS: At 6-year follow-up,
      these diagnoses are characterized by quantitative rather than qualitative
      differences in psychopathology, functionality, quality of life, and service
      engagement, with considerable overlap between them. These findings suggest that
      MDDP should join SZ, SA, and BD in a milieu of psychosis that transcends
      arbitrary boundaries.

PMID- 29575683
TI  - Accidental macular laser burn in a 12-year-old boy complicated with choroidal
      neovascularization: 4-year follow-up with spectral-domain optical coherence
      tomography.

PMID- 29575684
TI  - New mutations and an updated database for the patched-1 (PTCH1) gene.
AB  - BACKGROUND: Basal cell nevus syndrome (BCNS) is an autosomal dominant disorder
      characterized by multiple basal cell carcinomas (BCCs), maxillary keratocysts,
      and cerebral calcifications. BCNS most commonly is caused by a germline mutation
      in the patched-1 (PTCH1) gene. PTCH1 mutations are also described in patients
      with holoprosencephaly. METHODS: We have established a locus-specific database
      for the PTCH1 gene using the Leiden Open Variation Database (LOVD). We included
      117 new PTCH1 variations, in addition to 331 previously published unique PTCH1
      mutations. These new mutations were found in 141 patients who had a positive
      PTCH1 mutation analysis in either the VU University Medical Centre (VUMC) or
      Maastricht University Medical Centre (MUMC) between 1995 and 2015. RESULTS: The
      database contains 331 previously published unique PTCH1 mutations and 117 new
      PTCH1 variations. CONCLUSION: We have established a locus-specific database for
      the PTCH1 gene using the Leiden Open Variation Database (LOVD). The database
      provides an open collection for both clinicians and researchers and is accessible
      online at http://www.lovd.nl/PTCH1.

PMID- 29575685
TI  - High sensitivity and negative predictive value of sentinel lymph node biopsy in a
      retrospective early stage oral cavity cancer cohort in the Northern Netherlands.
AB  - OBJECTIVES: In cT1-2N0, oral squamous cell carcinoma (OSCC) occult metastases are
      detected in 23%-37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in
      head and neck cancer as a minimally invasive alternative for an elective neck
      dissection in neck staging. Meta-analyses of SLNB accuracy show heterogeneity in
      the existing studies for reference standards, imaging techniques and pathological
      examination. The aim of this study was to assess the sensitivity and negative
      predictive value (NPV) of the SLNB in detecting occult metastases in cT1-2N0 OSCC
      in a well-defined cohort. DESIGN: Retrospective study. The SLNB procedure
      consisted of lymphoscintigraphy, SPECT/CT-scanning and gamma probe detection.
      Routine follow-up was the reference standard for the SLNB negative neck.
      Histopathological examination of sentinel lymph nodes (SLN) consisted of step
      serial sectioning, haematoxylin-eosin and cytokeratin AE1/3 staining. SETTING:
      Two comprehensive oncology centres. PARTICIPANTS: A total of 91 consecutive
      patients with primary cT1-2N0 OSCC treated by primary resection and neck staging
      by SLNB procedure between 2008 and 2016. MAIN OUTCOME MEASURES: Sensitivity and
      negative predictive value. RESULTS: In all cases, SLNs were harvested. A total of
      25 (27%) patients had tumour-positive SLNs. The median follow-up was 32 months
      (range 2-104). Four patients were diagnosed with an isolated regional recurrence
      in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV.
      CONCLUSION: In our cohort, the SLNB detected occult metastases in early OSCC with
      85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for
      surgical staging of the neck in case of oral cT1-2N0 SCC.

PMID- 29575686
TI  - Photoinduced Copper-Catalyzed Coupling of Terminal Alkynes and Alkyl Iodides.
AB  - We have developed a photoinduced copper-catalyzed alkylation of terminal alkynes
      with primary, secondary, or tertiary alkyl iodides as electrophiles. The reaction
      has a broad substrate scope and can be successfully performed in the presence of
      ester, nitrile, aryl halide, ketone, sulfonamide, epoxide, alcohol, and amide
      functional groups. The alkylation is promoted by blue light (lambda~450 nm) and
      proceeds at room temperature in the absence of any additional metal catalysts.
      The use of a terpyridine ligand is essential for the success of the reaction and
      is shown to prevent photoinduced copper-catalyzed polymerization of the starting
      materials.

PMID- 29575687
TI  - An outbreak of Getah virus infection among pigs in China, 2017.
AB  - A Getah virus (GETV) outbreak occurred in a swine farm in Hunan, China, between
      June and July 2017. Approximately 200 piglets died 5-10 days after birth, and
      more than 150 pregnant sows had stillbirths or foetal mummies in this outbreak.
      GETV HuN1, isolated from the cerebrum of an infected piglet, shared a close
      evolutionary relationship with the Kochi/01/2005 strain, isolated from pigs in
      Japan. GETV was detected in the cerebral cortices of a dead foetus and in various
      organs of two infected piglets, thereby demonstrating that GETV can be
      transmitted through the placenta to infected newborn piglets with multiple tissue
      tropisms. Seroepizootiologic investigation of GETV revealed that a wide infection
      of GETV had been persisting in the farm between June 1 and July 17. In
      conclusion, clinical and laboratory diagnostics of the diseased pigs in this
      outbreak were consistent with GETV being the causative agent. To the best of our
      knowledge, this is the first unequivocal report of GETV in pigs in China.

PMID- 29575688
TI  - Piriformospora indica inoculation alleviates the adverse effect of NaCl stress on
      growth, gas exchange and chlorophyll fluorescence in tomato (Solanum lycopersicum
      L.).
AB  - Salinity is now an increasingly serious environmental issue that affects the
      growth and yield of many plants. In the present work, the influence of
      inoculation with the symbiotic fungus, Piriformospora indica, on gas exchange,
      water potential, osmolyte content, Na/K ratio and chlorophyll fluorescence of
      tomato plants under three salinity levels (0, 50, 100 and 150 mm NaCl) and three
      time periods (5, 10 and 15 days after exposure to salt) was investigated. Results
      indicate that P. indica inoculation improved growth parameters of tomato under
      salinity stress. This symbiotic fungus significantly increased photosynthetic
      pigment content under salinity, and more proline and glycine betaine accumulated
      in inoculated roots than in non-inoculated roots. P. indica further significantly
      improved K+ content and reduced Na+ level under salinity treatment. After
      inoculation with the endophytic fungus, leaf physiological parameters, such as
      water potential, net photosynthesis, stomatal conductance and transpiration, were
      all higher under the salt concentrations and durations compared with controls
      without P. indica. With increasing salt level and salt treatment duration, values
      of F0 and qP increased but Fm , Fv /Fm , F'v /F'm and NPQ declined in the
      controls, while inoculation with P. indica improved these values. The results
      indicate that the negative effects of NaCl on tomato plants were alleviated after
      P. indica inoculation, probably by improving physiological parameters such as
      water status and photosynthesis.

PMID- 29575689
TI  - Tunable Confinement for Bridging Single-Cell Manipulation and Single-Molecule DNA
      Linearization.
AB  - DNA linearization by nanoconfinement has offered a new avenue toward large-scale
      genome mapping. The ability to smoothly interface the widely different length
      scales from cell manipulation to DNA linearization is critical to the development
      of single-cell genomic mapping or sequencing technologies. Conventional
      nanochannel technologies for DNA analysis suffer from complex fabrication
      procedures, DNA stacking at the nanochannel entrance, and inefficient solution
      exchange. In this work, a dynamic and tunable confinement strategy is developed
      to manipulate and linearize genomic-length DNA molecules from a single cell. By
      leveraging pneumatic microvalve control and elastomeric collapse, an array of
      nanochannels with confining dimension down to 20 nm and length up to sub
      millimeter is created and can be dynamically tuned in size. The curved edges of
      the microvalve form gradual transitions from microscale to nanoscale confinement,
      smoothly facilitating DNA entry into the nanochannels. A unified
      micro/nanofluidic device that integrates single-cell trapping and lysis, DNA
      extraction, purification, labeling, and linearization is developed based on
      dynamically controllable nanochannels. Mbp-long DNA molecules are extracted
      directly from a single cell and in situ linearized in the nanochannels. The
      device provides a facile and promising platform to achieve the ultimate goal of
      single-cell, single-genome analysis.

PMID- 29575691
TI  - Individual factors influencing the duration of untreated psychosis.
AB  - AIM: Duration of untreated psychosis (DUP), or the time between onset of
      psychosis and treatment initiation, is a prognostic factor of schizophrenia.
      However, few studies evaluated the relative influence of individual-related
      factors on this duration. The objective of this study was to evaluate the
      influence of socio-demographic, clinical and cannabis use on DUP. METHODS: This
      study was part of a large prospective study in help-seeking individuals referred
      to our specialized early detection / intervention clinic in the Service Hospitalo
      Universitaire of Sainte-Anne Hospital in Paris (ICAAR study). We explored 33
      consecutive patients who crossed the CAARMS' threshold of psychosis. The DUP and
      cannabis consumption history were explored during the baseline comprehensive
      assessment using all available sources (direct interviews of patients, parents,
      practitioners). Correlations between socio-demographic, clinical and cannabis
      use, and DUP were studied. A multiple linear regression model was used to
      determine the variables that could significantly predict DUP. RESULTS: When
      considered individually, none of the socio-demographic and disease characteristic
      factors was associated with DUP, with the exception of level of education. In the
      multivariate analysis, age at inclusion, negative symptoms and history of
      cannabis use significantly influenced DUP. CONCLUSION: The determinants of DUP
      are multi-factorial and include individual centred factors, such as age, cannabis
      and negative symptoms. The identification of factors resulting in delayed access
      to care may promote the development of effective strategies to reduce DUP in
      early psychosis and target effective early intervention.

PMID- 29575690
TI  - Clarification of the Innervation of the Bladder, External Urethral Sphincter and
      Clitoris: A Neuronal Tracing Study in Female Mongrel Hound Dogs.
AB  - Many studies examining the innervation of genitourinary structures focus on
      either afferent or efferent inputs, or on only one structure of the system. We
      aimed to clarify innervation of the bladder, external urethral sphincter (EUS)
      and clitoris. Retrograde dyes were injected into each end organ in female dogs.
      Spinal cord, mid-bladder, and spinal, caudal mesenteric, sympathetic trunk and
      pelvic plexus ganglia were examined for retrograde dye-labeled neurons. Neurons
      retrogradely labeled from the bladder were found primarily in L7-S2 spinal
      ganglia, spinal cord lateral zona intermedia at S1-S3 levels, caudal mesenteric
      ganglia, T11-L2 and L6-S2 sympathetic trunk ganglia, and pelvic plexus ganglia.
      The mid-bladder wall contained many intramural ganglia neurons labeled
      anterogradely from the pelvic nerve, and intramural ganglia retrogradely labeled
      from dye labeling sites surrounding ureteral orifices. Neurons retrogradely
      labeled from the clitoris were found only in L7 and S1 spinal ganglia, L7-S3
      spinal cord lateral zona intermedia, and S1 sympathetic trunk ganglia, and caudal
      mesenteric ganglia. Neurons retrogradely labeled from the EUS were found in
      primarily at S1 and S2 spinal ganglia, spinal cord lamina IX at S1-S3, caudal
      mesenteric ganglia, and S1-S2 sympathetic trunk ganglia. Thus, direct inputs from
      the spinal cord to each end organ were identified, as well as multisynaptic
      circuits involving several ganglia, including intramural ganglia in the bladder
      wall. Knowledge of this complex circuitry of afferent and efferent inputs to
      genitourinary structures is necessary to understand and treat genitourinary
      dysfunction. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29575692
TI  - Effect of the in vivo application of granulocyte colony-stimulating factor on NK
      cells in bone marrow and peripheral blood.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been widely used in the field
      of allogeneic haematopoietic stem cell transplantation (allo-HSCT) for priming
      donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect
      stem cells more conveniently. Donor-derived natural killer (NK) cells have
      important antitumour functions and immune regulatory roles post-allo-HSCT. The
      aim of this study was to evaluate the effect of G-CSF on donors' NK cells in BM
      and PB. The percentage of NK cells among nuclear cells and lymphocyte was
      significantly decreased and led to increased ratio of T and NK cells in BM and PB
      post-G-CSF in vivo application. Relative expansion of CD56bri NK cells led to a
      decreased ratio of CD56dim and CD56bri NK subsets in BM and PB post-G-CSF in vivo
      application. The expression of CD62L, CD54, CD94, NKP30 and CXCR4 on NK cells was
      significantly increased in PB after G-CSF treatment. G-CSF treatment decreased
      the IFN-gamma-secreting NK population (NK1) dramatically in BM and PB, but
      increased the IL-13-secreting NK (NK2), TGF-beta-secreting NK (NK3) and IL-10
      secreting NK (NKr) populations significantly in BM. Clinical data demonstrated
      that higher doses of NK1 infused into the allograft correlated with an increased
      incidence of chronic graft-vs-host disease post-transplantation. Taken together,
      our results show that the in vivo application of G-CSF can modulate NK
      subpopulations, leading to an increased ratio of T and NK cells and decreased
      ratio of CD56dim and CD56bri NK cells as well as decreased NK1 populations in
      both PB and BM.

PMID- 29575693
TI  - Interaction of isolated cross-linked short actin oligomers with the skeletal
      muscle myosin motor domain.
AB  - The cyclical interaction between F-actin and myosin in muscle cells generates
      contractile force. The myosin motor domain hydrolyses ATP, resulting in
      conformational changes that are amplified by the myosin lever arm that links the
      motor domain to the rod domain. Recent cryo-electron microscopic data have
      provided a clear picture of the myosin-ATP-F-actin complex, but structural
      insights into other stages of the myosin-actin interaction have been less
      forthcoming. To address this issue, we cross-linked F-actin subunits between
      Cys374 and Lys191, and separated them by gel filtration. Purified actin-dimers, 
      trimers and -tetramers retained the ability to polymerize and to stimulate myosin
      subfragment 1 (myosin-S1) ATPase activity. To generate stable actin
      oligomer:myosin-S1 complexes, we blocked actin polymerization with gelsolin and
      Clostridium botulinum iota toxin-mediated ADP-ribosylation. After polymerization
      inhibition, actin-trimers and -tetramers retained the ability to stimulate the
      myosin-S1-ATPase, whereas the actin-dimer showed very little ATPase stimulation.
      We then analysed the stoichiometry and binding affinity of myosin-S1 to actin
      oligomers. Actin-trimers and -tetramers bound myosin-S1 in the absence of
      nucleotide; the trimer contains one myosin-S1 binding site. We calculated a
      dissociation constant (Kd ) of 1.1 * 10-10  m and 1.9 * 10-10  m for binding of
      native F-actin and the actin-trimer to myosin-S1, respectively. EM of the actin
      trimer:myosin-S1 complex demonstrated the presence of single particles of uniform
      size. Image reconstruction allowed a reasonable fit of the actin-trimer and
      myosin-S1 into the obtained density clearly showing binding of one myosin-S1
      molecule to the two long-pitch actins of the trimer, supporting the kinetic data.

PMID- 29575694
TI  - The correlation between active anterior rhinomanometry results and nasal
      obstruction symptoms scores after inferior turbinate reduction: A prospective
      cohort study about sixty-five patients.

PMID- 29575695
TI  - Construction of polyacrylamide/graphene oxide/gelatin/sodium alginate composite
      hydrogel with bioactivity for promoting Schwann cells growth.
AB  - Various hydrogels made from natural or synthetic polymers have been widely used
      in biologic tissues, drug delivery, and artificial implants due to their good
      biocompatibility, indicating a promising perspective in regenerative medicine. In
      the present study, a composite hydrogel named polyacrylamide/graphene
      oxide/gelatin/sodium alginate (PAM/GO/Gel/SA) for accelerating peripheral nerve
      regeneration was fabricated through in situ free radical polymerization for the
      first time. A series of physicochemical properties including morphology,
      porosity, swelling behaviors, component, mechanical properties, and in vitro
      degradation behavior of the prepared composite hydrogel were characterized. The
      effects of the composite hydrogel on Schwann cells growth were evaluated and the
      related molecular mechanism was further penetrated. The results showed that the
      prepared PAM/GO/Gel/SA composite hydrogels displayed different color appearance
      as the function of component variations. The surface morphology, components,
      swelling ratio, mechanical properties, and porosity were all changed with the
      concentration alteration of each ingredient, while no obvious degradation
      behavior was observed, indicating a controllable physicochemical property. The
      culture of cells exhibited that the composite hydrogels could well support the
      attachment and proliferation of Schwann cells. The gene expression levels of
      Sox10, GAP43, and myelin basic protein (MBP) in PGG0.5 SYR1 and PGG1 SYR0.5 were
      higher than those of NC. This study may provide important theoretical and
      experimental basis for the design and development of hydrogel scaffolds for nerve
      tissue engineering application. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 1951-1964, 2018.

PMID- 29575696
TI  - Food Restriction is Required to Preserve the Antisteatotic Effects of Central
      Leptin in the Liver of Middle-Aged Rats.
AB  - OBJECTIVE: Aging is a significant risk factor for the development of obesity and
      hepatic steatosis associated with insulin and leptin resistance. Food restriction
      (FR) is commonly used for reducing body weight (BW), adiposity, and liver
      steatosis. Thus, this study aimed to determine whether FR in middle-aged rats can
      recover the central leptin antisteatotic effects observed in the liver in young
      animals. METHODS: Two groups of 4-month-old Wistar rats were fed ad libitum (AL)
      or were on FR for 3 months. At 7 months of age, both groups were centrally
      treated with rat leptin (0.2 MUg/d, 7 days) or saline. RESULTS: Central leptin
      reduced food intake and BW, but not the hepatic triglyceride content, in 7-month
      old rats fed AL. However, in 7-month-old FR rats, leptin did not affect BW but
      markedly reduced serum leptin, serum and hepatic triglyceride levels, and the
      expression of hepatic lipogenic genes. In addition, central leptin decreased
      serum and hepatic endogenous norepinephrine levels of FR rats, exerting a
      homeostatic effect beyond its antisteatotic actions. CONCLUSIONS: These findings
      suggest that in middle-aged rats, moderate FR is required for both preserving the
      antisteatotic actions of central leptin and avoiding excessive weight loss.

PMID- 29575697
TI  - Fetal Development of Fasciae around the Arm and Thigh Muscles: A Study Using Late
      Stage Fetuses.
AB  - To obtain a better understanding of multi-laminar deep fascia covering skeletal
      muscles, we examined nondecalcified histological sections of the arm and thigh of
      20 human fetuses aged 25-33 weeks. Morphologies of the fasciae varied between
      sites and specimens, but the initial morphology was most likely to be a thin and
      loose sheet on the external surface of the muscles (fascia-1 or F1). When the F1
      became wavy, thick and tight, it was detached from the muscle surface. Beneath
      the F1, the second lamina of fascia (F2) appeared on the muscle surface and it
      was also detached. In this manner at 25-33 weeks' gestation, fasciae covering the
      triceps and vastus lateralis muscles had a three-layered configuration (F1, F2,
      and F3). Due to significant individual variations, this process was not
      correlated to the ages and sizes of specimens. Muscle contractions might
      facilitate the detachment. In these muscles, the intramuscular tendon joined the
      F2 or F3 and the latter became thick and aponeurotic. Along the finally developed
      lamina, muscle fibers carried a desmin-positive spot for insertion. Increased
      laminae were accompanied by a reduced number of CD68-positive macrophages and,
      nerves were absent, near the developing fascia. In contrast to skin ligaments or
      superficial fasciae showing de novo development in loose tissue, a deep or muscle
      covering fascia seemed to originate from the skeletal muscle itself at the
      surface, and this process was repeated to produce multi-layered fascia. Depending
      on sites, collagen fibers were added by the intramuscular tendon. Anat Rec, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29575698
TI  - Effects of Short-Term Normobaric Hypoxic Walking Training on Energetics and
      Mechanics of Gait in Adults with Obesity.
AB  - OBJECTIVE: The aim of this study was to compare the effects of short-term hypoxic
      versus normoxic training at preferred walking speed (PWS) on energetics,
      mechanics, efficiency, and metabolic risk markers in individuals with obesity.
      METHODS: Twenty-three subjects with obesity performed nine 1-hour sessions at PWS
      under hypoxia (3,000 m, n = 12; BMI: 34.0 +/- 0.8 kg/m2 ) or normoxia (360 m, n =
      11; BMI: 32.9 +/- 0.8 kg/m2 ). Participants performed six 5-minute walking trials
      at different speeds (PWS, 0.56, 0.83, 1.11, 1.39, and 1.67 m/s). The net energy
      cost, external mechanical work, and rated perceived exertion (RPE) were measured
      at these speeds. Body composition and blood samples were collected. RESULTS: PWS
      tended to be slower under hypoxia than normoxia (-6.7%; P = 0.092) during the
      training, and this difference reached significance the third week (-8.9%; P =
      0.05). After training, PWS significantly increased (+ 8.2%; P <= 0.001), while
      RPE decreased (P = 0.005). Ankle range of motion (P = 0.03) and vertical
      displacement of the center of mass (P = 0.02) significantly increased in both
      groups. CONCLUSIONS: A walking training program under hypoxia at slower PWS than
      in normoxia elicited similar responses in metabolic risk factors, energetics, and
      mechanics of walking in individuals with obesity. Both programs increased PWS,
      decreased RPE, and induced gait-pattern adaptations, which protected against
      orthopedic injury in these individuals.

PMID- 29575699
TI  - Natural Polyphenols Selectively Inhibit beta-Carbonic Anhydrase from the Dandruff
      Producing Fungus Malassezia globosa: Activity and Modeling Studies.
AB  - Around 50 % of the worldwide population is affected by dandruff, which is
      triggered by a variety of factors. The yeast Malassezia globosa has been labeled
      as the most probable causative agent for the onset of dandruff. The beta-carbonic
      anhydrase (CA) of MgCA was recently validated as an anti-dandruff target, with
      its inhibition being responsible for in vivo growth defects in the fungus. As
      classical CA inhibitors of the sulfonamide type give rise to permeability
      problems through biological membranes, finding non-sulfonamide alternatives for
      MgCA inhibition is of considerable interest in the cosmetic field. We recently
      screened a large library of human (h) CA inhibitors for MgCA inhibition,
      including different chemotypes, such as monothiocarbamates, dithiocarbamates,
      phenols, and benzoxaboroles. Herein, we expanded the research toward new MgCA
      inhibitors by considering a set of natural polyphenols (including flavones,
      flavonols, flavanones, flavanols, isoflavones, and depsides) that exhibited MgCA
      inhibitory activity in the micromolar range, as well as selectivity for the
      fungal isozyme over off-target human isoforms. The binding mode of representative
      derivatives within the MgCA catalytic cleft was investigated by docking studies
      using a homology-built model.

PMID- 29575700
TI  - Antimicrobial-resistant Enterobacteriaceae recovered from companion animal and
      livestock environments.
AB  - Antimicrobial-resistant bacteria represent an important concern impacting both
      veterinary medicine and public health. The rising prevalence of extended-spectrum
      beta-lactamase (ESBL), AmpC beta-lactamase, carbapenemase (CRE) and
      fluoroquinolone-resistant Enterobacteriaceae continually decreases the efficiency
      of clinically important antibiotics. Moreover, the potential for zoonotic
      transmission of antibiotic-resistant enteric bacteria increases the risk to
      public health. Our objective was to estimate the prevalence of specific
      antibiotic-resistant bacteria on human contact surfaces in various animal
      environments. Environmental surface samples were collected from companion animal
      shelters, private equine facilities, dairy farms, livestock auction markets and
      livestock areas of county fairs using electrostatic cloths. Samples were screened
      for Enterobacteriaceae expressing AmpC, ESBL, CRE or fluoroquinolone resistance
      using selective media. Livestock auction markets and county fairs had higher
      levels of bacteria expressing both cephalosporin and fluoroquinolone resistance
      than did equine, dairy, and companion animal environments. Equine facilities
      harboured more bacteria expressing cephalosporin resistance than companion animal
      shelters, but less fluoroquinolone resistance. The regular use of extended
      spectrum cephalosporins in livestock populations could account for the increased
      levels of cephalosporin resistance in livestock environments compared to
      companion animal and equine facilities. Human surfaces, as well as shared human
      and animal surfaces, were contaminated with resistant bacteria regardless of
      species environment. Detecting these bacteria on common human contact surfaces
      suggests that the environment can serve as a reservoir for the zoonotic
      transmission of antibiotic-resistant bacteria and resistance genes. Identifying
      interventions to lower the prevalence of antibiotic-resistant bacteria in animal
      environments will protect both animal and public health.

PMID- 29575701
TI  - Pupillary changes after laser peripheral iridotomy.

PMID- 29575702
TI  - Fluorogenic Ag+ -Tetrazolate Aggregation Enables Efficient Fluorescent Biological
      Silver Staining.
AB  - Silver staining, which exploits the special bioaffinity and the chromogenic
      reduction of silver ions, is an indispensable visualization method in biology. It
      is a most popular method for in-gel protein detection. However, it is limited by
      run-to-run variability, background staining, inability for protein
      quantification, and limited compatibility with mass spectroscopic (MS) analysis;
      limitations that are largely attributed to the tricky chromogenic visualization.
      Herein, we reported a novel water-soluble fluorogenic Ag+ probe, the sensing
      mechanism of which is based on an aggregation-induced emission (AIE) process
      driven by tetrazolate-Ag+ interactions. The fluorogenic sensing can substitute
      the chromogenic reaction, leading to a new fluorescence silver staining method.
      This new staining method offers sensitive detection of total proteins in
      polyacrylamide gels with a broad linear dynamic range and robust operations that
      rival the silver nitrate stain and the best fluorescent stains.

PMID- 29575703
TI  - Oxidative Asymmetric Aza-Friedel-Crafts Alkylation of Indoles with 3-Indolinone-2
      carboxylates Catalyzed by a BINOL Phosphoric Acid and Promoted by DDQ.
AB  - An asymmetric aza-Friedel-Crafts alkylation reaction between indoles and
      indolenines that were derived in situ from 3-indolinone-2-carboxylates has been
      developed by using 3,3'-bis(triphenylsilyl)-1,1'-binaphthyl-2,2'-diyl hydrogen
      phosphate as a catalyst. The reaction proceeded under mild conditions and
      provided chiral indol-3-yl-3-indolinone-2-carboxylate derivatives in good yields
      with excellent ee values (up to 98.6 %). Similarly, the Mannich-type addition of
      indoline-3-ones to indolenines provided heterodimers with vicinal chiral
      quaternary centers. This method was successfully applied to the construction of
      the core structure of trigonoliimine C.

PMID- 29575704
TI  - Essential role of Rpd3-dependent lysine modification in the growth, development
      and virulence of Beauveria bassiana.
AB  - Rpd3 is a class I histone deacetylase that reverses lysine acetylation thus
      influencing cellular processes and functions. However, its role in fungal insect
      pathogens has not been explored yet. Here we show that Rpd3-dependent lysine
      modification and gene expression orchestrate growth, conidiation and virulence in
      Beauveria bassiana. Deletion of Rpd3 resulted in severe growth defects on various
      carbon/nitrogen sources, 97% reduction in conidiation capacity and drastic
      attenuation in virulence. These phenotypes concurred with differential expression
      of 1479 proteins and hyperacetylation or hypoacetylation of 2227 lysine residues
      on 1134 proteins. Many of these proteins fell into carbon/nitrogen metabolism and
      cell rescue/defence/virulence, indicating vital roles of Rpd3-dependent protein
      expression and lysine modification in the fungal growth and virulence.
      Intriguingly, lysine residues of four core histones (H2A, H2B, H3 and H4) and
      many histone acetyltransferases were also hyper- or hypoacetylated in Deltarpd3,
      suggesting direct and indirect roles for Rpd3 in genome-wide lysine modification.
      However, crucial development activators were transcriptionally repressed and not
      found in either proteome or acetylome. Single/double-site-directed H3K9/K14
      mutations for hyper/hypoacetylation exerted significant impacts on conidiation
      and dimorphic transition crucial for fungal virulence. Altogether, Rpd3 mediates
      growth, asexual development and virulence through transcriptional/translational
      regulation and posttranslational lysine modification in B. bassiana.

PMID- 29575705
TI  - Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2
      Hydroxypyrimidine/Pyrimidin-2(1H)-one Tautomers.
AB  - A facile access to optically active cyclic ureas was developed through palladium
      catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy
      group with up to 99 % ee. Mechanistic studies indicated that reaction pathway
      proceed through hydrogenation of C=N of the oxo tautomer pyrimidin-2(1H)-one,
      acid-catalyzed isomerization of enamine-imine, and hydrogenation of imine
      pathway. In addition, the chiral cyclic ureas are readily converted into useful
      chiral 1,3-diamine and thiourea derivatives without loss of optical purity.

PMID- 29575706
TI  - Revealing the Self-Degradation Mechanisms in Methylammonium Lead Iodide
      Perovskites in Dark and Vacuum.
AB  - Organic-inorganic lead halide perovskite phases segregate (and their structures
      degrade) under illumination, exhibiting a poor stability with hysteresis and
      producing halide accumulation at the surface.In this work, we observed structural
      and interfacial dissociation in methylammonium lead iodide (CH3 NH3 PbI3 )
      perovskites even under dark and vacuum conditions. Here, we investigate the
      origin and consequences of self-degradation in CH3 NH3 PbI3 perovskites stored in
      the dark under vacuum. Diffraction and photoelectron spectroscopic studies reveal
      the structural dissociation of perovskites into PbI2 , which further dissociates
      into metallic lead (Pb0 ) and I2- ions, collectively degrading the perovskite
      stability. Using TOF-SIMS analysis, AuI2- formation was directly observed, and it
      was found that an interplay between CH3 NH3+ , I3- , and mobile I- ions
      continuously regenerates more I2- ions, which diffuse to the surface even in the
      absence of light. Besides, halide diffusion causes a concentration gradient
      between Pb0 and I2- and creates other ionic traps (PbI2- , PbI- ) that segregate
      as clusters at the perovskite/gold interface. A shift of the onset of the
      absorption band edge towards shorter wavelengths was also observed by absorption
      spectroscopy, indicating the formation of defect species upon aging in the dark
      under vacuum.

PMID- 29575707
TI  - Predictors of student use of an electronic record.
AB  - BACKGROUND: Little is known on ambulatory clerkship students' use of an
      electronic medical record (EMR). We investigated students' use of recommended EMR
      tasks across different types of sites and studied the predictors of these
      recommended tasks. METHODS: Students documented how often they performed
      recommended EMR tasks and suggested improvements to enhance EMR use. We compared
      student performance of recommended tasks across different types of sites using
      chi2 tests and the Fisher's exact test. We performed regression analyses to
      investigate factors predicting students' performance of EMR tasks. Two faculty
      members read all of the suggested improvements and agreed on themes. RESULTS:
      From January 2014 to June 2015, 263 of 295 Family and Community Medicine
      Clerkship (FCMC) students (89.2%) were at sites that used an EMR. Of the 263
      students, 68.4% typed their own note into the EMR, but only 31.2% entered orders
      and 27.8% entered prescriptions for their teacher to sign. Students' rating of
      the orientation to the EMR predicted their use of all EMR tasks. The number of
      years that the teaching site used an EMR predicted the students' use of some
      tasks. Suggested improvements included a better orientation to the EMR, more use
      of the EMR, and access to a computer and the EMR. Little is known on ambulatory
      clerkship students' use of an electronic medical record DISCUSSION: Many students
      did not perform recommended EMR tasks. To help more students learn EMR tasks,
      clinical teachers can offer students a detailed orientation to their EMR, provide
      them with access to a computer and the EMR, and give them the opportunity to
      perform recommended EMR tasks, including typing their own note and entering
      orders and prescriptions.

PMID- 29575708
TI  - The impact of aerobic exercise training with vascular occlusion in patients with
      chronic heart failure.
AB  - AIMS: This study aimed to evaluate the impact of aerobic exercise training with
      vascular occlusion in patients with chronic heart failure. METHODS AND RESULTS:
      Thirty patients with post-infarction heart failure were randomized to an
      interventional exercise group (IG; n = 15) or a control exercise group (CG; n =
      15). Exercise was performed at an intensity of 40-70% of the peak VO2 /W for 6
      months. Patients in the IG remained seated on the saddle of the cycle ergometer
      with their feet on the pedals. Pneumatic tourniquets were applied to the proximal
      ends of their thighs with appropriate pressure resulting in a 40-80 mmHg increase
      in the systolic blood pressure that is required for vascular occlusion (208.7 +/-
      7.4 mmHg). We evaluated the safety and efficacy of the intervention and its
      effect on exercise capacity and serum BNP levels. There were no significant
      differences between the IG and CG in patient characteristics at study entry. Peak
      VO2 /W in the IG significantly increased compared with that in the CG; the change
      in the serum BNP levels was significantly larger in the IG than in the CG.
      CONCLUSIONS: These results suggest that aerobic exercise training with vascular
      occlusion can improve exercise capacity and serum BNP levels in patients with
      chronic heart failure.

PMID- 29575709
TI  - Highly Efficient Hydrogenation of Levulinic Acid into gamma-Valerolactone using
      an Iron Pincer Complex.
AB  - The search for nonprecious-metal-based catalysts for the synthesis of gamma
      valerolactone (GVL) through hydrogenation of levulinic acid and its derivatives
      in an efficient fashion is of great interest and importance, as GVL is an
      important a sustainable liquid. We herein report a pincer iron complex that can
      efficiently catalyze the hydrogenation of levulinic acid and methyl levulinate
      into GVL, achieving a turnover number of up to 23 000 and a turnover frequency of
      1917 h-1 . This iron-based catalyst also enabled the formation of GVL from
      various biomass-derived carbohydrates in aqueous solution, thus paving a new way
      toward a renewable chemical industry.

PMID- 29575710
TI  - Divergently Seeking Clarification: The Emergence of Clarification Interaction.
AB  - Clarification requests, queries posed in response to a "problematic" (misheard,
      misunderstood, etc.) utterance, are a challenge to mainstream semantic theories
      because they call into question notions such as "shared content" or "the
      context." Given their strong parallelism requirements, elliptical clarification
      requests introduce in addition significant complexities concerning the need for
      long-term maintenance of non-semantic information in context. In this paper, we
      consider a puzzle concerning the emergence of elliptical clarification requests
      in child English: Data from the Belfast and Manchester corpora from CHILDES
      demonstrate that reprise fragments, the highest frequency clarification request
      construction among adults, emerges with significant delay in comparison with
      reprise sluices, bare wh-phrases used to request clarification. This is a
      puzzling finding a priori: first, since reprise fragments are by most plausible
      measures the most readily available clarification request form in that it
      involves mere repetition of material primed by the previous utterance and
      children have the ability to repeat parts of the previous utterance from the
      earliest stages of speech. Moreover, as we show, reprise fragments predominate-in
      some cases vastly so, over sluicing in the input of fragmentary clarification
      requests available to the child-and it would, therefore, be difficult to
      construct an explanation for order of emergence primarily based on frequency of
      the construction in the children's input. Our account is based on grammatical
      explication of the difference between the constructions, how constructional
      difference is represented in a hierarchy of constructions, and in terms of a
      notion of semantic complexity that suggests reprise sluicing is, in fact, less
      complex than reprise fragments.

PMID- 29575711
TI  - Hearing aids in patients with vestibular schwannoma: Interest of the auditory
      brainstem responses.
AB  - OBJECTIVE: Hearing loss subsequent to a unilateral vestibular schwannoma (VS) has
      an impact on the social life of non-operated patients. We investigated the
      utility of auditory brainstem responses (ABRs) for predicting the results of
      auditory rehabilitation in such patients. DESIGN: Prospective study. SETTING:
      University tertiary medical centre. PARTICIPANTS: We collected the demographic,
      audiometric, ABR and imaging data of non-operated patients with unilateral VS. A
      hearing aid trial was performed over 1 month. We assessed auditory performance
      following the auditory rehabilitation according to the ABR results. Patients with
      distinct waves (I, III and V) were included in the "distinct ABR" group and
      patients with no ABR were included in the "desynchronised ABR" group. MAIN
      OUTCOME MEASURES: Following the trial, audiometric performance and quality of
      life were evaluated with the Glasgow Benefit Inventory (GBI). SUBJECTS AND
      METHOD: We collected the demographic, audiometric, ABR and imaging data of non
      operated patients with unilateral VS. A hearing aid trial was performed over 1
      month. Following the trial, audiometric performance and quality of life were
      evaluated with the Glasgow Benefit Inventory (GBI). We assessed auditory
      performance following the auditory rehabilitation according to the ABR results.
      Patients with distinct waves (I, III and V) were included in the "distinct ABR"
      group and patients with no ABR were included in the "desynchronised ABR" group.
      RESULTS: In total, 25 patients were included in this prospective study; 15 in the
      "distinct ABR" group and 10 in the "desynchronised ABR" group. The speech
      recognition threshold (SRT, P < .0001; W = -120) and speech discrimination score
      (P = .0005; W = 78) were significantly improved in the aided vs unaided
      conditions. These improvements were not observed in the "desynchronised ABR"
      group for the SRT (P = .48; W = -10) and word recognition score (P = .06; W =
      15). Ninety-three per cent of the patients in the "distinct ABR" group kept
      significantly (P = .04) the hearing aids following the trial compared to 20% in
      the "desynchronised ABR" group. CONCLUSIONS: Auditory brainstem responses can
      help to predict the auditory performance following auditory rehabilitation in
      unilateral non-operated VS patients.

PMID- 29575712
TI  - Structure Elucidation of the Main Tetrahydroxyxanthones of Hypericum Seeds and
      Investigations into the Testa Structure.
AB  - Seeds from Hypericum species have recently been identified as an interesting
      source of xanthone derivatives. Extraction of seeds from H. perforatum with MeOH
      and subsequent concentration via polyamide adsorption yielded a fraction enriched
      in tetrahydroxyxanthones (THX), which were further semipurified by silica gel
      chromatography. Based on tentative structure assignment of the two main THX X1
      and X2 by NMR a total synthesis was performed for both compounds (THX 1 and 2,
      respectively), starting with an Ullmann ether synthesis. The synthesized 1 and 2
      were characterized via 1D- and 2D-NMR methods as well as by LC/HR-MS analysis and
      proven to be 1,4,6,7-THX (1) and 1,2,6,7-THX (2). Final structure assignment of
      the natural Hypericum THX constituents was accomplished by comparing
      chromatographic and spectroscopic data (LC/MSn and GC/MS) with those of 1 and 2
      which were obtained by synthesis. Beyond, investigations into the seeds of H.
      perforatum and H. tetrapterum by scanning electron microscopy (SEM) provided
      insights of the structure of the testa (seed coat), which is established by two
      cell layers, with the lignified sclerenchyma presumably being the depository of
      the xanthones.

PMID- 29575714
TI  - Blood flow-restricted exercise: Providing more bang for buck in trained athletes?

PMID- 29575715
TI  - Waste.

PMID- 29575713
TI  - Functional transcriptomic annotation and protein-protein interaction analysis
      identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer.
AB  - Although early stage ovarian cancer is in most cases a curable disease, some
      patients relapse even with appropriate adjuvant treatment. Therefore, the
      identification of patient and tumor characteristics to better stratify risk and
      guide rational drug development is desirable. Using transcriptomic functional
      annotation followed by protein-protein interacting (PPI) network analyses, we
      identified functions that were upregulated and associated with detrimental
      outcome in patients with early stage ovarian cancer. Some of the identified
      functions included cell cycle, cell division, signal transduction/protein
      modification, cellular response to extracellular stimuli or transcription
      regulation, among others. Genes within these functions included AURKA, AURKB,
      CDK1, BIRC5, or CHEK1 among others. Of note, the histone-lysine N
      methyltransferase (EZH2) and the ubiquitin-conjugating enzyme E2C (UBE2C) genes
      were found to be upregulated and amplified in 10% and 6% of tumors, respectively.
      Of note, EZH2 and UBE2C were identified as principal interacting proteins of
      druggable networks. In conclusion, we describe a set of genes overexpressed in
      ovarian cancer with potential for therapeutic intervention including EZH2 and
      UBE2C.

PMID- 29575716
TI  - Standardization of extracellular vesicle measurements by flow cytometry through
      vesicle diameter approximation.
AB  - : Essentials Platelet extracellular vesicles (EVs) concentrations measured by
      flow cytometers are incomparable. A model is applied to convert ambiguous scatter
      units to EV diameter in nanometer. Most included flow cytometers lack the
      sensitivity to detect EVs of 600 nm and smaller. The model outperforms
      polystyrene beads for comparability of platelet EV concentrations. SUMMARY:
      Background Detection of extracellular vesicles (EVs) by flow cytometry has poor
      interlaboratory comparability, owing to differences in flow cytometer (FCM)
      sensitivity. Previous workshops distributed polystyrene beads to set a scatter
      based diameter gate in order to improve the comparability of EV concentration
      measurements. However, polystyrene beads provide limited insights into the
      diameter of detected EVs. Objectives To evaluate gates based on the estimated
      diameter of EVs instead of beads. Methods A calibration bead mixture and platelet
      EV samples were distributed to 33 participants. Beads and a light scattering
      model were used to set EV diameter gates in order to measure the concentration of
      CD61-phycoerythrin-positive platelet EVs. Results Of the 46 evaluated FCMs, 21
      FCMs detected the 600-1200-nm EV diameter gate. The 1200-3000-nm EV diameter gate
      was detected by 31 FCMs, with a measured EV concentration interlaboratory
      variability of 81% as compared with 139% with the bead diameter gate. Part of the
      variation in both approaches is caused by precipitation in some of the provided
      platelet EV samples. Flow rate calibration proved essential because systems
      configured to 60 MUL min-1 differed six-fold in measured flow rates between
      instruments. Conclusions EV diameter gates improve the interlaboratory
      variability as compared with previous approaches. Of the evaluated FCMs, 24%
      could not detect 400-nm polystyrene beads, and such instruments have limited
      utility for EV research. Finally, considerable differences were observed in
      sensitivity between optically similar instruments, indicating that maintenance
      and training affect the sensitivity.

PMID- 29575717
TI  - Benefits of antifungal therapy in asthma patients with airway mycosis: A
      retrospective cohort analysis.
AB  - INTRODUCTION: Fungal airway infection (airway mycosis) is increasingly recognized
      as a cause of asthma and related disorders. However, prior controlled studies of
      patients treated with antifungal antibiotics have produced conflicting results.
      Our objective is to measure the effect of antifungal therapy in moderate to
      severe adult asthmatics with positive fungal sputum cultures in a single center
      referral-based academic practice. METHODS: We retrospectively evaluated 41
      patients with asthma and culture-proven airway mycosis treated with either
      terbinafine, fluconazole, itraconazole, voriconazole, or posaconazole for 4 to
      >12 weeks together with standard bronchodilator and anti-inflammatory agents.
      Asthma control (1 = very poorly controlled; 2 = not well controlled; and 3 = well
      controlled), peak expiratory flow rates (PEFR), serum total IgE, and absolute
      blood eosinophil counts before and after antifungal therapy were assessed. In
      comparison, we also studied nine patients with airway mycosis and moderate to
      severe asthma who received standard therapy but no antifungals. RESULTS:
      Treatment with azole-based and allylamine antifungals was associated with
      improved asthma control (mean change in asthma control 1.72-2.25; p = 0.004),
      increased PEFR (69.4% predicted to 79.3% predicted, p = 0.0011) and markedly
      reduced serum IgE levels (1,075 kU/L to 463 kU/L, p = 0.0005) and blood
      eosinophil counts (Mean absolute count 530-275, p = 0.0095). Reduction in
      symptoms, medication use, and relapse rates decreased as duration of therapy
      increased. Asthmatics on standard therapy who did not receive antifungals showed
      no improvement in asthma symptoms or PEFR. Antifungals were usually well
      tolerated, but discontinuation (12.2%) and relapse (50%) rates were relatively
      high. CONCLUSION: Antifungals help control symptoms in a subset of asthmatics
      with culture-proven airway mycosis. Additional randomized clinical trials are
      warranted to extend and validate these findings.

PMID- 29575719
TI  - Significance and indications for reoperative portoenterostomy in biliary atresia
      in light of long-term outcome.
AB  - BACKGROUND: Among biliary atresia (BA) patients undergoing revision following
      failed portoenterostomy, long-term native liver survival (NLS), physical
      condition, and indications for revision were explored. METHODS: From 1977-2015,
      33 of 95 BA patients (35%) at our institution underwent revision. Ten- and 20
      year NLS rates (NLSRs) and biochemical statuses of 20-year-old native liver
      survivors were compared between post-portoenterostomy BA patients with and
      without history of revision. Factors associated with 10-year NLS following
      revision and optimal cut-offs for potential predictors were analyzed. RESULTS:
      Overall 10- and 20-year NLSRs were 57% and 54%, respectively. Ten- and 20-year
      NLSRs were 49% and 45% in the revision group and 63% and 61% in the non-revision
      group, respectively. Among 20-year-old native liver survivors, differences in
      admission rates between ages 10-20 years were not significant for cholangitis
      (revision, 46%; non-revision, 40%; P = 0.30) or portal hypertension (revision,
      38%; non-revision, 15%; P = 0.21). Differences in hepatobiliary function
      associated blood tests between these groups at 20 years old were only significant
      for aspartate aminotransferase (P = 0.02) and gamma-glutamyl transpeptidase (P =
      0.047). Among potential predictors of 10-year NLS that we investigated, rate of
      change in total bilirubin (TB) over the first month post-portoenterostomy was
      best (P = 0.0019), and the receiver operating characteristic curve revealed an
      optimal cut-off for this first-month change in TB of -3.7 mg/dl (area under the
      curve, 0.85; sensitivity, 0.79; specificity, 0.83). CONCLUSIONS: In approximately
      half of the patients, revision provided 10- and 20-year NLS, and biochemical
      status at 20 years old was comparable across revision and non-revision patients.
      Rate of change in TB during the first month post-portoenterostomy offers a
      sensitive predictor of revision.

PMID- 29575718
TI  - Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal
      cancer and clinical features suggestive of Lynch Syndrome.
AB  - Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome,
      caused by germline mutations in one of the major genes involved in mismatch
      repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline
      deletions in EPCAM have been also associated to the syndrome. Most of the
      pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene
      variants include missense, nonsense, frameshift mutations, large genomic
      rearrangements and splice-site variants and most of the studies reporting the
      molecular characterization of LS families have been conducted outside South
      America. In this study, we analyzed 60 unrelated probands diagnosed with
      colorectal cancer and LS criteria. Testing for germline mutations and/or
      rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and
      MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic
      variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these,
      approximately one-third were gene rearrangements. In addition, nine variants of
      uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands
      analyzed. Other four novel variants were identified, only in MLH1. Our results
      suggest that MSH6 pathogenic variants are not common among Brazilian LS probands
      diagnosed with CRC and that MMR gene rearrangements account for a significant
      proportion of the germline variants in this population underscoring the need to
      include rearrangement analysis in the molecular testing of Brazilian individuals
      with suspected Lynch syndrome.

PMID- 29575720
TI  - Polydopamine Particle-Filled Shape-Memory Polyurethane Composites with Fast Near
      Infrared Light Responsibility.
AB  - A new kind of fast near-infrared (NIR) light-responsive shape-memory polymer
      composites was prepared by introducing polydopamine particles (PDAPs) into
      commercial shape-memory polyurethane (SMPU). The toughness and strength of the
      polydopamine-particle-filled polyurethane composites (SMPU-PDAPs) were
      significantly enhanced with the addition of PDAPs due to the strong interface
      interaction between PDAPs and polyurethane segments. Owing to the outstanding
      photothermal effect of PDAPs, the composites exhibit a rapid light-responsive
      shape-memory process in 60 s with a PDAPs content of 0.01 wt%. Due to the
      excellent dispersion and convenient preparation method, PDAPs have great
      potential to be used as high-efficiency and environmentally friendly fillers to
      obtain novel photoactive functional polymer composites.

PMID- 29575721
TI  - Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone
      Based Cannabinoid Receptor Type 2 Ligands.
AB  - In recent years, cannabinoid type 2 receptors (CB2 R) have emerged as promising
      therapeutic targets in a wide variety of diseases. Selective ligands of CB2 R are
      devoid of the psychoactive effects typically observed for CB1 R ligands. Based on
      our recent studies on a class of pyridazinone 4-carboxamides, further structural
      modifications of the pyridazinone core were made to better investigate the
      structure-activity relationships for this promising scaffold with the aim to
      develop potent CB2 R ligands. In binding assays, two of the new synthesized
      compounds [6-(3,4-dichlorophenyl)-2-(4-fluorobenzyl)-cis-N-(4-methylcyclohexyl)-3
      oxo-2,3-dihydropyridazine-4-carboxamide (2) and 6-(4-chloro-3-methylphenyl)-cis-N
      (4-methylcyclohexyl)-3-oxo-2-pentyl-2,3-dihydropyridazine-4-carboxamide (22)]
      showed high CB2 R affinity, with Ki values of 2.1 and 1.6 nm, respectively. In
      addition, functional assays of these compounds and other new active related
      derivatives revealed their pharmacological profiles as CB2 R inverse agonists.
      Compound 22 displayed the highest CB2 R selectivity and potency, presenting a
      favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling
      study revealed how 22 produces inverse agonism through blocking the movement of
      the toggle-switch residue, W6.48.

PMID- 29575722
TI  - Differential effects of transient and sustained activation of BDNF-TrkB
      signaling.
AB  - Brain-derived neurotrophic factor (BDNF) serves a pleiotropic role in the central
      nervous system, ranging from promoting neuronal survival and differentiation
      during development and synaptic modulation in the adult. An important, yet
      unanswered question is how BDNF could serve such diverse functions, sometimes in
      the same cell. At least two modes of BDNF actions have been elucidated so far
      based on BDNF signaling kinetics and/or the activity status of the responding
      neurons. Acute and gradual increases in extracellular BDNF concentrations elicit,
      respectively, transient and sustained activation of TrkB receptor and its
      downstream signaling, leading to differential molecular and cellular functions.
      In cultured neurons, sustained TrkB activation promotes neuronal dendritic
      arborization and spinogenesis, whereas transient TrkB activation facilitates
      dendritic growth and spine morphogenesis. In hippocampal slices, slow delivery of
      BDNF facilitates LTP, whereas fast application of BDNF enhances basal synaptic
      transmission in schaffer collateral synapses. High-frequency stimulation of
      neurons converts BDNF-induced TrkB signaling from a transient to a sustained
      mode. These initial insights lay the foundation for future investigation of the
      BDNF-TrkB pathway, and analogous signaling pathways to gain a comprehensive
      understanding to enable translational research. (c) 2018 Wiley Periodicals, Inc.
      Develop Neurobiol 78: 647-659, 2018.

PMID- 29575723
TI  - Copper Affects the Location of Zinc in Bimetallic Ion-Exchanged Mordenite.
AB  - Bimetallic ion exchange on a zeolite often impacts its catalytic properties
      compared to its monometallic counterparts. Here, we address the synergistic
      effect of simultaneous copper and zinc ion exchange on mordenite (MOR), as found
      earlier for dimethyl ether (DME) carbonylation. Samples with various Cu/Zn ratios
      were characterized by diffuse-reflectance infrared Fourier-transform spectroscopy
      (DRIFTS) in the 3600 and 720 cm-1 regions, pore distribution analysis through Ar
      physisorption, X-ray photoelectron spectroscopy (XPS), temperature-programmed
      reduction (TPR), and transmission electron microscopy (TEM). When ion-exchanged
      alone, copper preferentially occupies 12-membered rings, whereas zinc occupies 8
      membered rings. In bimetallic combinations, the zinc addition was found to
      prevent the copper from sintering into nanoparticles and to increase its
      coordination strength to the zeolite. At a Cu/Zn ratio of 0.25 (for MOR with
      Si/Al=6.5), copper promotes zinc ion exchange into 12-membered rings, more
      specifically, into T4 sites that are known for the formation of the coke
      precursor in DME carbonylation on a MOR. The sites became blocked during the
      bimetallic ion exchange, leading to suppressed catalyst deactivation. The study
      contributes to the understanding of mutual ion effects in bimetallic exchanged
      zeolites and highlights the major role of copper as a governing factor in
      determining the location of co-exchanged zinc on a MOR.

PMID- 29575725
TI  - Redox-Driven Symmetry Change for Terbium(III) Bis(porphyrinato) Double-Decker
      Complexes by the Azimuthal Rotation of the Porphyrin Macrocycles.
AB  - Molecular structures for three oxidation forms (anion, radical, and cation) of
      terbium(III) bis(porphyrinato) double-decker complexes have been systematically
      studied. We found that the redox state controls the azimuthal rotation angle
      (phi) between the two porphyrin macrocycles. For [TbIII (tpp)2 ]n (tpp:
      tetraphenylporphyrinato, n=-1, 0, and +1), phi decreases at each stage of the
      oxidation process. The decrease in phi is due to the higher steric repulsion
      between the phenyl rings on the porphyrin macrocycle and the beta hydrogen atoms
      on the other porphyrin macrocycle, which results from the shorter interfacial
      distance between the two porphyrin macrocycles. Conversely, phi=45 degrees  for
      both [TbIII (oep)2 ]-1 and [TbIII (oep)2 ]0 (oep: octaethylporphyrinato), but
      phi=36 degrees  for [TbIII (oep)2 ]+1 . Theoretical calculations suggest that the
      smaller azimuthal rotation angle of the cation form is due to the electronic
      interaction in the doubly oxidized ligand system.

PMID- 29575724
TI  - Cross-sectional survey of biosimilar insulin utilization in Asia: The Joint Asia
      Diabetes Evaluation Program.
AB  - AIMS/INTRODUCTION: Biosimilar insulin can reduce treatment costs, although the
      extent of its use is largely unknown. We examined biosimilar insulin use and its
      associations with the quality of glycemic control using the Joint Asia Diabetes
      Evaluation register. MATERIALS AND METHODS: We carried out a cross-sectional
      analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the
      Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related
      terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared
      clinical profiles between biosimilar and originator insulin users. Multivariate
      analysis was performed to assess the association of biosimilar insulin compared
      with originator insulin with dosage, glycated hemoglobin and hypoglycemia events.
      RESULTS: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In
      four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin
      users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%;
      the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%).
      Biosimilar insulin users were younger and had higher body mass index, glycated
      hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin
      users. These associations were non-significant after adjustment for confounders.
      Only age, college education, diabetes education, lipid control, physical activity
      and history of cardiovascular complications were independently associated with
      these quality measures. CONCLUSIONS: Biosimilar insulin use is not uncommon in
      Asia. Data exclusion due to incomplete capturing of brand names suggests possibly
      higher use. The multiple determinants of the quality of glycemic control call for
      establishment of prospective cohorts and diabetes registers to monitor the safety
      and efficacy of different brands of biosimilar insulin and their impacts on
      clinical outcomes.

PMID- 29575726
TI  - p53 mediated regulation of coactivator associated arginine methyltransferase 1
      (CARM1) expression is critical for suppression of adipogenesis.
AB  - Coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is a type I
      arginine methyltransferase that mediates transcriptional activation via
      methylation of histone H3 on R17, R26, and R42. CARM1 is also a coactivator of
      transcription of various transcription factors such as NF-kB, MEF2C, beta
      catenin, p53, PPAR-gamma etc. CARM1 has been functionally implicated in
      maintenance of pluripotency, cellular differentiation, and tumorigenesis; where
      its expression status plays an important role. Although its expression has been
      shown to be regulated by a few miRNAs in different contexts at post
      transcriptional level, transcriptional regulation of CARM1 gene is still
      unexplored. In this report we demonstrate that CARM1 is a p53 responsive gene,
      where p53 could suppress CARM1 promoter-driven luciferase expression. CARM1 gene
      expression was found to be repressed by p53 in 3T3L1 preadipocytes when activated
      with Nutlin-3a treatment. Ectopic overexpression of CARM1 could rescue inhibitory
      effect of p53 on adipogenesis, suggesting a role of p53-CARM1 axis of regulation
      operational in the context of adipocyte differentiation. p53 and CARM1 showed
      antagonistic regulatory influence on PPAR-gamma expression; which suggests that
      p53-mediated suppression of adipogenesis could be partly via repression of CARM1
      expression. Taken together these observations provide convincing mechanistic
      explanation for p53 function in the context of adipocyte differentiation process.

PMID- 29575727
TI  - Discovery of novel pyrrolopyrimidine/pyrazolopyrimidine derivatives bearing 1,2,3
      triazole moiety as c-Met kinase inhibitors.
AB  - Six series of pyrrolo[2,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives
      bearing 1,2,3-triazole moiety were designed and synthesized, and some bio
      evaluation was also carried out. As a result, four points can be summarized:
      Firstly, some of compounds exhibited excellent cytotoxicity activity and
      selectivity with the IC50 values in single-digit MUm level. In particular, the
      most promising compound 16d showed equal activity to lead compound foretinib
      against A549, HepG2, and MCF-7 cell lines, with the IC50 values of 4.79 +/- 0.82,
      2.03 +/- 0.39, and 2.90 +/- 0.43 MUm, respectively. Secondly, the SARs and
      docking studies indicated that the in vitro antitumor activity of pyrrolo[2,3
      d]pyrimidine derivatives bearing 1,2,3-triazole moiety was superior to the
      pyrazolo[3,4-d]pyrimidine derivatives bearing 1,2,3-triazole moiety. Thirdly,
      three selected compounds (16d, 18d, and 20d) were further evaluated for
      inhibitory activity against the c-Met kinase, and the 16d could inhibit the c-Met
      kinase selectively by experiments of enzyme-based selectivity. What is more, 16d
      could induce apoptosis of HepG2 cells and inhibitor the cell cycle of HepG2 on
      G2/M phase by acridine orange staining and cell cycle experiments, respectively.

PMID- 29575728
TI  - The Role of Mentoring in Leadership Development.
AB  - This chapter discusses the role of mentoring in facilitating leadership
      development for students throughout the educational pipeline. Related literature
      is summarized and practical guidance is provided for designing, implementing, and
      evaluating programs with a focus toward developing students as leaders.

PMID- 29575729
TI  - The Role of Mentoring, Coaching, and Advising in Developing Leadership Identity.
AB  - A changing world calls for leaders with the capacity for collaborative, socially
      responsible forms of leadership. The development of this capacity is connected to
      the growth of one's leadership identity. This chapter addresses how mentors,
      advisors, and coaches play a role in helping students formulate and grow in their
      leadership identity, and therefore their capacity for exercising leadership.

PMID- 29575730
TI  - Assessing Student Leadership Development From Mentoring, Coaching, and Advising.
AB  - Leadership educators must demonstrate the contributions their programs make to
      the learning and development of students. This chapter provides an overview of
      assessment principles for educators to apply in their practices of mentoring,
      coaching, and advising.

PMID- 29575731
TI  - Leadership Development in Digital Spaces Through Mentoring, Coaching, and
      Advising.
AB  - The increasing population of students engaging in online and digital spaces poses
      unique leadership development challenges in mentoring, coaching, and advising.
      This chapter discusses the importance of using digital spaces for leadership
      development and students' sense of belonging.

PMID- 29575733
TI  - The Role of Advising in Leadership Development.
AB  - This chapter addresses the roles and responsibilities of advising; specifically,
      how advisors can cultivate both individual and group settings to be important
      teaching and learning environments and how to advise with leadership development
      in mind.

PMID- 29575732
TI  - Distinguishing Mentoring, Coaching, and Advising for Leadership Development.
AB  - Mentoring, coaching, and advising are often confused as similar interactions with
      developmental intent, yet their scope, purpose, and utility in leadership
      development are distinct. The purpose of this chapter is to provide clarity as to
      what constitutes mentoring, coaching, and advising for leadership development and
      to compare and contrast each relationship type.

PMID- 29575734
TI  - Cultural Competence and Inclusivity in Mentoring, Coaching, and Advising.
AB  - This chapter asserts that effective mentors, coaches, and advisors must be
      culturally competent in order to engage in inclusive practice with emerging
      leaders. Specific recommendations are provided.

PMID- 29575735
TI  - Editors' Notes.

PMID- 29575736
TI  - The Role of Coaching in Leadership Development.
AB  - Leadership coaching can be productive in maximizing a leader's development. But
      to make leadership coaching work effectively for students, as opposed to
      executives, this chapter offers guidance on key concepts and practices from the
      Center for Creative Leadership's Coaching Framework.

PMID- 29575737
TI  - The Impact of Ultrasound on the Use and Efficacy of Intraarticular Glucocorticoid
      Injections in Early Rheumatoid Arthritis: Secondary Analyses From a Randomized
      Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regimen.
AB  - OBJECTIVE: Intraarticular glucocorticoid injections are common in rheumatoid
      arthritis (RA) treatment. This study was undertaken to investigate whether
      ultrasound in combination with clinical examination is better than clinical
      examination alone at identifying joints that will benefit from intraarticular
      injections, and to compare the efficacy of ultrasound-guided versus palpation
      guided procedures. METHODS: In the treat-to-target Aiming for Remission in
      Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasonography
      in a Clinical Tight Control Regimen (ARCTIC), patients with early RA were
      randomized 1:1 to follow-up with or without ultrasound. In addition to disease
      modifying antirheumatic drugs, intraarticular glucocorticoids were used to treat
      inflamed joints. The distribution of injections was assessed in both study
      groups. The relationship of clinical and ultrasound findings at the time of
      injection with treatment efficacy was examined, with non-swollen joint at the
      next visit as the outcome measure. Treatment success was compared across study
      groups to evaluate ultrasound-guided versus palpation-guided procedures. RESULTS:
      More injections were administered in the ultrasound group than in the
      conventional strategy group (n = 770 versus 548), especially in intercarpal
      joints (n = 58 versus 5) and metatarsophalangeal joints (n = 200 versus 104).
      Injecting clinically swollen joints without power Doppler (PD) activity on
      ultrasound was not efficacious compared to not injecting (odds ratio [OR] 1.3; P
      = 0.59). Efficacy was best in swollen joints (OR 9.0; P = 0.001) and non-swollen
      joints (OR 8.4; P = 0.016) with moderate PD activity. Treatment success was
      similar for the ultrasound-guided and palpation-guided procedures. CONCLUSION:
      Our findings indicate that the efficacy of intraarticular glucocorticoid
      injections varies according to ultrasound findings at the time of injection,
      supporting the use of ultrasound as a tool to select joints that will benefit
      from intraarticular injections. However, ultrasound needle guidance was not
      superior to palpation guidance.

PMID- 29575738
TI  - First live birth after uterus transplantation in the United States.
AB  - Uterus transplantation has proven to be a successful treatment for women with
      absolute uterine infertility, caused either by the absence of a uterus or the
      presence of a nonfunctioning uterus. We report the first birth of a healthy child
      following uterus transplantation in the United States, from a recipient of a
      uterus allograft procured from an altruistic living donor. Two major
      modifications from the previously reported live births characterized this uterus
      transplant. First, the transplanted uterus relied upon and sustained the
      pregnancy while having only the utero-ovarian vein as venous outflow. The
      implication is a significantly simplified living donor surgery that paves the way
      for minimally invasive laparoscopic or robot-assisted techniques for the donor
      hysterectomy. Second, the time from transplantation to embryo transfer was
      significantly shortened from prior protocols, allowing for an overall shorter
      exposure to immunosuppression by the recipient and lowering the risk for
      potential adverse effects from these medications.

PMID- 29575739
TI  - Numerical zero-dimensional hepatic artery hemodynamics model for balloon-occluded
      transarterial chemoembolization.
AB  - Balloon-occluded transarterial chemoembolization (B-TACE) is a valuable treatment
      option for patients with inoperable malignant tumors in the liver. Balloon
      occluded transarterial chemoembolization consists of the transcatheter infusion
      of an anticancer drug mixture and embolic agents. Contrary to conventional TACE,
      B-TACE is performed via an artery-occluding microballoon catheter, which makes
      the blood flow to redistribute due to the intra- and extrahepatic arterial
      collateral circulation. Several recent studies have stressed the importance of
      the redistribution of blood flow in enhancing the treatment outcome. In the
      present study, the geometries of a representative hepatic artery and the
      communicating arcades (CAs) are modeled. An in silico zero-dimensional
      hemodynamic model is created by characterizing the geometry and the boundary
      conditions and then is validated in vitro. The role of CAs is assessed by
      combining 2 cancer scenarios and 2 catheter locations. The importance of the
      diameter of the CAs is also studied. Results show that occluding a main artery
      leads to collateral circulation and CAs start to play a role in blood-flow
      redistribution. In summary, numerical zero-dimensional simulations permit a fast
      and reliable approach for exploring the blood-flow redistribution caused by the
      occlusion of a main artery, and this approach could be used during B-TACE
      planning.

PMID- 29575740
TI  - Stable pneumorectum using an inline glove - a cost-effective technique to
      facilitate transanal total mesorectal excision.
AB  - AIM: Transanal total mesorectal excision (taTME) is a novel approach for
      resection of the rectum. Use of a standard insufflator to create pneumorectum,
      however, results in bellowing-large heaving motions from insufflation of air that
      can frustrate surgery. We report the successful application of our technique,
      stable pneumorectum using an inline glove (SPRING), for the performance of
      transanal rectal excision in a series of 17 patients using a standard
      laparoscopic insufflator. METHOD: A retrospective review of 17 patients using the
      SPRING technique was performed between October 2015 and October 2016.
      Characteristics of these patients were evaluated, and technique-related short
      term outcome was reviewed. RESULTS: The SPRING technique was successfully used in
      patients who underwent both minimally invasive (n = 14) and open (n = 3)
      approaches in the abdominal stage of the surgery. In the 12 patients who had
      rectal cancer for whom SPRING was used to facilitate taTME there were no
      conversions to an alternative access for rectal resection, the median duration of
      the TME part of the operation was 95 min (62-147) and there was one R1 resection
      (8%). Billowing was not a significant problem in any of the 17 patients during
      the surgery. CONCLUSION: In this case series we have successfully shown the
      feasibility of the SPRING technique as a practical and cost-effective solution to
      the problem of billowing during taTME.

PMID- 29575741
TI  - Historical development of percutaneous transhepatic biliary interventions.

PMID- 29575743
TI  - Potential of Lactobacillus plantarum IBB3036 and Lactobacillus salivarius IBB3154
      to persistence in chicken after in ovo delivery.
AB  - The aim of this study was to characterize and compare selected Lactobacillus
      strains originating from different environments (cow milk and hen feces) with
      respect to their applicative potential to colonize gastrointestinal track of
      chickens before hatching from an egg. In vitro phenotypic characterization of
      lactobacilli strains included the investigation of the important prerequisites
      for persistence in gastrointestinal tract, such as a capability to survive in the
      presence of bile salts and at low pH, enzymatic and sugar metabolic profiles,
      adhesion abilities, and resistance to osmolytes, temperature, and antibiotics.
      Regarding the resistance of lactobacilli to most of the various stress factors
      tested, the milk isolate Lactobacillus plantarum IBB3036 showed better abilities
      than the chicken feces isolate Lactobacillus salivarius IBB3154. However,
      regarding the acidification tolerance and adherence ability, L. salivarius
      IBB3154 revealed better characteristics. Use of these two selected lactobacilli
      isolates together with proper prebiotics resulted in the preparation of two S1
      and S2 bioformulations, which were injected in ovo into hen Cobb500 FF fertilized
      eggs. Furthermore, in vivo tests assessing the persistence of L. plantarum
      IBB3036 and L. salivarius IBB3154 in the chicken gastrointestinal tract was
      monitored by PCR-based classical and quantitative techniques and revealed the
      presence of both strains in fecal samples collected 3 days after hatching.
      Subsequently, the number of L. salivarius IBB3154 increased significantly in the
      chicken intestine, whereas the presence of L. plantarum IBB3036 was gradually
      decreased.

PMID- 29575742
TI  - Deregulation of secondary metabolism in a histone deacetylase mutant of
      Penicillium chrysogenum.
AB  - The Pc21 g14570 gene of Penicillium chrysogenum encodes an ortholog of a class 2
      histone deacetylase termed HdaA which may play a role in epigenetic regulation of
      secondary metabolism. Deletion of the hdaA gene induces a significant pleiotropic
      effect on the expression of a set of polyketide synthase (PKS) and nonribosomal
      peptide synthetase (NRPS)-encoding genes. The deletion mutant exhibits a
      decreased conidial pigmentation that is related to a reduced expression of the
      PKS gene Pc21 g16000 (pks17) responsible for the production of the pigment
      precursor naphtha-gamma-pyrone. Moreover, the hdaA deletion caused decreased
      levels of the yellow pigment chrysogine that is associated with the
      downregulation of the NRPS-encoding gene Pc21 g12630 and associated biosynthetic
      gene cluster. In contrast, transcriptional activation of the sorbicillinoids
      biosynthetic gene cluster occurred concomitantly with the overproduction of
      associated compounds . A new compound was detected in the deletion strain that
      was observed only under conditions of sorbicillinoids production, suggesting
      crosstalk between biosynthetic gene clusters. Our present results show that an
      epigenomic approach can be successfully applied for the activation of secondary
      metabolism in industrial strains of P. chrysogenum.

PMID- 29575744
TI  - Evaluation of information presented within soft tissue sarcoma histopathology
      reports in the United States: 2012-2015.
AB  - Despite the existence of the American College of Veterinary Pathology guidelines
      for tumour biopsy specimens, anecdotally the authors' have seen inconsistency of
      reporting of information on the pathology report for canine soft tissue sarcomas
      (STSs). If crucial aspects are not reported this can result in slower or impeded
      patient care. This retrospective study evaluated 255 STS histopathology reports
      submitted from across the United States. Reports were evaluated by a single
      observer to assess for information contained in 5 main categories: patient
      history and signalment, gross and microscopic description, grading, histologic
      margins and the comments section. Inclusion criteria for histopathology reports
      included a final diagnosis of STS, having a microscopic description and resulting
      from the initial surgical resection. The majority of the reports stated the
      patient signalment (91.2%) and clinical history (90.8%). However, only 64.8% of
      the reports had a gross description of the specimen. Histologic margin
      description was present in 229 reports (91.6%), however, only 149 reports (59.6%)
      stated an objective measurement of these margins. Histologic classification was
      stated in 50.0% of the reports, while grade was given on 97.2% of the reports.
      Variability in histopathologic reporting including histologic margin description
      for resected canine STS was identified. Given surgical treatment is the mainstay
      for STS and histopathological assessment plays an important role in determination
      of whether additional surgery, radiation or chemotherapy is needed.
      Standardization or checklists like the American College of Pathology utilize may
      be helpful to ensure histopathologic characteristics are reported that may guide
      further treatment recommendations.

PMID- 29575745
TI  - Evaluation of two-dimensional Bruch's membrane opening minimum rim area for
      glaucoma diagnostics in a large patient cohort.
AB  - PURPOSE: To characterize the two-dimensional parameter Bruch's membrane opening
      minimum rim area (BMO-MRA) in spectral domain optical coherence tomography (SD
      OCT) of the optic nerve head (ONH) compared to minimum rim width (BMO-MRW) and
      retinal nerve fibre layer (RNFL) thickness in a large patient cohort. METHODS:
      Case-control, cross-sectional study of 705 eyes of 445 participants. A total of
      449 eyes with glaucoma, 67 eyes with ocular hypertension and 189 healthy
      controls, underwent SD-OCT and confocal laser scanning tomography (CSLT), visual
      field testing and clinical examination. Morphometric ONH parameters, visual field
      function and diagnostic power were compared. Main outcome measures were SD-OCT
      derived BMO-MRA, BMO-MRW, RNFL thickness and CSLT-derived rim area (DM-RA).
      RESULTS: Mean ONH area was 2.11 +/- 0.57 mm2 ; mean BMO area was 1.89 +/- 0.45
      mm2 . Correlation of mean deviation in visual field to morphometric parameters
      was rho = 0.70, (p < 0.001) for RNFL thickness, rho = 0.68 (p < 0.001) for BMO
      MRA, rho = 0.66 (p < 0.001) for BMO-MRW. These correlations were not
      significantly different (p > 0.05), while DM-RA correlated significantly worse
      (rho = 0.55; p < 0.001). In receiver operating characteristics, the calculated
      area under the curve (AUC) and sensitivity at 90% specificity to differentiate
      glaucoma were 0.87% and 70.1% for BMO-MRA, 0.86% and 68.1% for RNFL thickness,
      0.84% and 66.0% for BMO-MRW, 0.82% and 51.3% for DM-RA. CONCLUSIONS: In a
      heterogenous clinical cohort of glaucoma patients, all analysed SD-OCT parameters
      excel DM-RA of CSLT. The two-dimensional parameter BMO-MRA shows comparable
      levels of diagnostic power to detect glaucoma compared to established parameters
      BMO-MRW and RNFL thickness. Given higher comparability between ONH sizes, BMO-MRA
      might become an additional standard tool in SD-OCT imaging for glaucoma.

PMID- 29575746
TI  - Experience of associative stigma in parents of adolescents at risk for psychosis.
AB  - AIM: This qualitative study examined the lived experience of associative stigma
      for parents of adolescents at clinical high risk for psychosis. A central goal
      was to empower families to tell their stories and to use the themes that emerge
      from this narrative data to make recommendations that might support families
      coping with a loved one being diagnosed with risk for psychosis. METHODS: Twelve
      parents of adolescents diagnosed with the clinical high risk for psychosis
      syndrome were interviewed using a semi-structured approach. The qualitative study
      employed Interpretative Phenomenological Analysis (IPA) to focus on experiences
      of associative stigma and the way parents make sense of these experiences.
      RESULTS: From these interviews, the researcher identified themes and subthemes
      categorized into major domains that represent topics particularly relevant to
      these 12 parents. Two main domains emerged as particularly salient to parents'
      experiences with associative stigma: perceptions of stigma and coping with
      stigma. CONCLUSIONS: Participants' insights demonstrated increased experience of
      stigma associated with psychotic-like symptoms as compared to other psychiatric
      symptoms, attempts to balance fighting against stigma with the privacy needs of
      adolescents, and participation in research as less stigmatizing than non
      specialty care. Stigma impacted treatment-seeking and participation in family
      groups that were seen as both potentially supportive and threatening. The
      interviews provided an opportunity for these families to voice their unique
      experiences, which expands the literature on the topic of caregivers of
      adolescents at risk for psychosis as treatment programs for the clinical high
      risk syndrome expand across the United States.

PMID- 29575748
TI  - Porous Cobalt Oxynitride Nanosheets for Efficient Electrocatalytic Water
      Oxidation.
AB  - Exploring efficient and cheap oxygen evolution reaction (OER) electrocatalysts is
      of great significance for electrochemical water splitting. Herein, we
      successfully prepared an efficient ternary electrocatalyst of porous cobalt
      oxynitride (Co3 Ox Ny ) nanosheets by a simple nitridation strategy.
      Specifically, CoON PNS-400 (cobalt oxynitride with porous nanosheet structure
      obtained at 400 o C) offered a low OER overpotential of 0.23 V to achieve the
      catalytic current density of 10 mA cm-2 and a small Tafel slope of 48 mV dec-1 in
      alkali media, outperforming most of the first-row transition-metal-based OER
      electrocatalysts. The calculated density of states (DOS) analysis and electron
      spin resonance (ESR) measurements revealed that the introduction of foreign N
      atoms into pristine Co3 O4 nanosheets can optimize the electronic structure and
      create more oxygen vacancies, thus leading to enhanced electrical conductivity.
      Density functional theory (DFT) calculations demonstrated that the foreign N
      atoms can also improve the energetics for OER by modulating the free energy for
      adsorbed intermediates (OOH*, OH*, O*), further improving the OER
      electrocatalytic activity of CoON PNS-400. This work provides a possibility for
      rationally designing ternary transition-metal compounds as advanced OER
      electrocatalysts.

PMID- 29575749
TI  - Characterization of a novel allele, HLA-C*02:135N, by full-length gene sequencing
      in a bone marrow donor.
AB  - A frameshift because of a two-nucleotide deletion results in an HLA-C null
      allele, HLA-C*02:135N.

PMID- 29575750
TI  - Let's talk about sex: A rigorous statistical framework to assign the sex of
      individuals from reduced-representation sequencing data.
AB  - Molecular markers have been used to identify the sex of sampled individuals for
      several decades, but the time-consuming development phase prevented their
      application in many systems. Recently, a growing number of papers have applied
      reduced-representation sequencing (RRS) protocols to the identification of sex
      specific markers without the use of test crosses or prior genomic information.
      While such an approach has great advantages in terms of versatility and ease of
      use, the "shotgun sequencing" nature of RRS data sets leads to a high amount of
      missing data, which results in statistical challenges to the confident assignment
      of sex to individuals. In this issue of Molecular Ecology Resources, Stovall et
      al. (Molecular Ecology Resources, 18, 2018) provide a statistical framework to
      answer two questions: (1) how many individuals of one sex only must possess a
      genotype for this locus to be considered significantly sex-specific? and (2) How
      many sex-specific loci must an individual of unknown sex possess (in a given data
      set) to be confidently assigned a sex? The statistical pipeline introduced, and
      applied to samples of New Zealand fur seal (Arctocephalus forsteri) to identify
      90 sex-specific loci, should be broadly applicable to a large number of species
      and constitutes a nice addition to the molecular ecology toolkit in the genomics
      era.

PMID- 29575751
TI  - Numerical approximation of the electromechanical coupling in the left ventricle
      with inclusion of the Purkinje network.
AB  - In this work, we consider the numerical approximation of the electromechanical
      coupling in the left ventricle with inclusion of the Purkinje network. The
      mathematical model couples the 3D elastodynamics and bidomain equations for the
      electrophysiology in the myocardium with the 1D monodomain equation in the
      Purkinje network. For the numerical solution of the coupled problem, we consider
      a fixed-point iterative algorithm that enables a partitioned solution of the
      myocardium and Purkinje network problems. Different levels of myocardium-Purkinje
      network splitting are considered and analyzed. The results are compared with
      those obtained using standard strategies proposed in the literature to trigger
      the electrical activation. Finally, we present a numerical study that, although
      performed in an idealized computational domain, features all the physiological
      issues that characterize a heartbeat simulation, including the initiation of the
      signal in the Purkinje network and the systolic and diastolic phases.

PMID- 29575752
TI  - Rapid on-site evaluation using telecytology: A major cancer center experience.
AB  - BACKGROUND: Rapid on-site evaluation (ROSE) with cytology preparations plays a
      critical role in minimally invasive procedures. The time spent by a pathologist
      performing ROSE is unpredictable and could be used for more cost-effective
      activities. The solution encountered by several institutions to address this
      issue is the use of telecytology (TC). This study analyzes the experience of
      using telecytology for ROSE in a major cancer center over a period of over 2
      years. METHODS: A retrospective analysis of all remote TC evaluations for
      adequacy on fine needle aspiration (FNA) and touch preparations (TP) of core
      biopsies (CB) performed at a major cancer center was performed. The preliminary
      adequacy assessment was then compared to the adequacy assessment at final
      diagnosis. RESULTS: A total of 12 949 adequacy assessments were analyzed. The
      most common sites biopsied in our institution were lymph node, lung, and liver.
      There were 7725 adequacy assessments for CB (59.7%), while adequacy assessment
      for FNA specimens represented 40.3% (n = 5224) of the total number of specimens
      evaluated by ROSE. Perfect concordance between initial adequacy assessment and
      the adequacy assessment at final cytologic diagnosis was 93% (12 049/12 949). The
      final diagnosis adequacy upgrade rate was 6.7% (n = 863), and the adequacy
      downgrade (a specimen considered adequate on-site that was determined to be
      nondiagnostic on final examination) was 0.3% (n = 37). CONCLUSIONS: TC can be
      easily implemented with the current technologies available. It is cost-effective
      and allows for better patient care with a more efficient use of the pathologist's
      time and laboratory resources.

PMID- 29575753
TI  - A graphical method for comparing nocturnal oxygen saturation profiles in
      individuals and populations: Application to healthy infants and preterm neonates.
AB  - STUDY OBJECTIVES: Pulse-oximetry (SpO2 ) allows the identification of important
      clinical physiology. However, summary statistics such as mean values and
      desaturation incidence do not capture the complexity of the information contained
      within continuous recordings. The aim of this study was to develop an objective
      method to quantify important SpO2 characteristics; and assess its utility in
      healthy infant and preterm neonate cohorts. METHODS: An algorithm was developed
      to calculate the desaturation incidence, depth, and duration. These variables are
      presented using three plots: SpO2 cumulative-frequency relationship; desaturation
      depth versus incidence; desaturation-duration versus incidence. This method was
      applied to two populations who underwent nocturnal pulse-oximetry: (1) thirty
      four healthy term infants studied at 2-weeks, 3, 6, 12, and 24-months of age and
      (2) thirty-seven neonates born <26 weeks and studied at discharge from NICU (37
      44 weeks post-conceptual age). RESULTS: The maturation in healthy infants was
      characterized by reduced desaturation index (27.2/h vs 3.3/h at 2-weeks and 24
      months, P < 0.01), and increased percentage of desaturation events >=6-s in
      duration (27.8% vs 43.2% at 2-weeks and 3-months, P < 0.01). Compared with term
      infants, preterm infants had a greater desaturation incidence (54.8/h vs 27.2/h,
      P < 0.01), and these desaturations were deeper (52.9% vs 37.6% were >=6% below
      baseline, P < 0.01). The incidence of longer desaturations (>=14-s) in preterm
      infants was correlated with healthcare utilization over the first 24-months (r =
      0.63, P < 0.01). CONCLUSIONS: This tool allows the objective comparison of
      extended oximetry recordings between groups and for individuals; and serves as a
      basis for the development of reference ranges for populations.

PMID- 29575754
TI  - Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of
      Macrophage Migration Inhibitory Factor.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that
      is implicated in the regulation of inflammation, cell proliferation, and
      neurological disorders. MIF is also an enzyme that functions as a keto-enol
      tautomerase. Most potent MIF tautomerase inhibitors incorporate a phenol, which
      hydrogen bonds to Asn97 in the active site. Starting from a 113-MUm docking hit,
      we report results of structure-based and computer-aided design that have provided
      substituted pyrazoles as phenol alternatives with potencies of 60-70 nm. Crystal
      structures of complexes of MIF with the pyrazoles highlight the contributions of
      hydrogen bonding with Lys32 and Asn97, and aryl-aryl interactions with Tyr36,
      Tyr95, and Phe113 to the binding.

PMID- 29575755
TI  - Peri-implant parameters, tumor necrosis factor-alpha, and interleukin-1 beta
      levels in vaping individuals.
AB  - BACKGROUND: To the author's knowledge, there has been no study that has assessed
      clinical, radiographic, and immunological peri-implant parameters among
      individuals vaping e-cigarette (e-cig). PURPOSE: This pilot study aimed to
      compare clinical and radiographic peri-implant parameters and levels of tumor
      necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta levels among
      individuals vaping e-cigs and never smoker (NS). MATERIALS AND METHODS: Forty
      seven individuals vaping e-cigs (group-1) and 45 NS (group-2) were included.
      Demographic and implant-related data were collected using a structured baseline
      questionnaire. Peri-implant plaque index (PI), bleeding on probing (BOP), and
      probing depth (PD) were recorded and peri-implant bone loss (PIBL) were assessed
      using standardized digital radiographs. Enzyme-linked immunosorbent assay was
      used to assess the levels of TNF-alpha and IL-1beta in peri-implant sulcular
      fluid. RESULTS: Bleeding on probing showed statistically significantly higher
      values in group-2 patients as compared to group-1 patients (P < .01). Probing
      depth >= 4 mm and PIBL was statistically significantly higher in group-1 patients
      as compared to group-2 patients (P < .05). Mean concentrations of TNF-alpha (P <
      .001) and IL-1beta (P < .01) were statistically significantly increased in
      individuals in group 1 as compared with group 2. A significant positive
      correlations were found between TNF-alpha levels and BOP (P = .024) and PIBL (P =
      .016); and significant positive correlation was found between IL-1beta and PIBL
      (P = .018) in group 1, respectively. CONCLUSIONS: Clinical and radiographic peri
      implant parameters are compromised among vaping individuals. Increased levels of
      proinflammatory cytokines in peri-implant sulcular fluid may suggest greater
      local inflammatory response in vaping individuals for peri-implant inflammation.

PMID- 29575756
TI  - Major research prize awarded to wheat researchers.

PMID- 29575757
TI  - (Pro)renin receptor: Involvement in diabetic retinopathy and development of
      molecular targeted therapy.
AB  - The renin-angiotensin system (RAS), a crucial regulator of systemic blood
      pressure (circulatory RAS), plays distinct roles in pathological angiogenesis and
      inflammation in various organs (tissue RAS), such as diabetic microvascular
      complications. Using ocular clinical samples and animal disease models, we
      elucidated molecular mechanisms in which tissue RAS excites the expression of
      vascular endothelial growth factor (VEGF)-A responsible for retinal inflammation
      and angiogenesis, the two major pathological events in diabetic retinopathy (DR).
      Furthermore, we showed the involvement of (pro)renin receptor [(P)RR] in retinal
      RAS activation and its concurrent intracellular signal transduction (e.g.,
      extracellular signal-regulated kinase); namely, the (P)RR-induced dual pathogenic
      bioactivity referred to as the receptor-associated prorenin system. Indeed,
      neovascular endothelial cells in the fibrovascular tissue collected from eyes
      with proliferative DR were immunoreactive for the receptor-associated prorenin
      system components including prorenin, (P)RR, phosphorylated extracellular signal
      regulated kinase and VEGF-A. Protein levels of soluble (P)RR increased with its
      positive correlations with prorenin, renin enzymatic activity and VEGF in the
      vitreous of proliferative DR eyes, suggesting a close link between (P)RR and VEGF
      A-driven angiogenic activity. Furthermore, we revealed an unsuspected, PAPS
      independent role of (P)RR in glucose-induced oxidative stress. Recently, we
      developed an innovative single-strand ribonucleic acid interference molecule
      selectively targeting human and mouse (P)RR, and confirmed its efficacy in
      suppressing diabetes-induced retinal inflammation in mice. Our data using
      clinical samples and animal models suggested the significant implication of (P)RR
      in the pathogenesis of DR, and the potential usefulness of the ribonucleic acid
      interference molecule as a therapeutic agent to attenuate ocular inflammation and
      angiogenesis.

PMID- 29575758
TI  - A selenoprotein T-derived peptide protects the heart against
      ischaemia/reperfusion injury through inhibition of apoptosis and oxidative
      stress.
AB  - AIM: Selenoprotein T (SelT or SELENOT) is a novel thioredoxin-like enzyme whose
      genetic ablation in mice results in early embryonic lethality. SelT exerts an
      essential cytoprotective action during development and after injury through its
      redox-active catalytic site. This study aimed to determine the expression and
      regulation of SelT in the mammalian heart in normal and pathological conditions
      and to evaluate the cardioprotective effect of a SelT-derived peptide, SelT43
      52(PSELT) encompassing the redox motif which is key to its function, against
      ischaemia/reperfusion(I/R) injury. METHODS: We used the isolated Langendorff rat
      heart model and different analyses by immunohistochemistry, Western blot and
      ELISA. RESULTS: We found that SelT expression is very abundant in embryo but is
      undetectable in adult heart. However, SelT expression was tremendously increased
      after I/R. PSELT (5 nmol/L) was able to induce pharmacological post-conditioning
      cardioprotection as evidenced by a significant recovery of contractility (dLVP)
      and reduction of infarct size (IS), without changes in cardiac contracture
      (LVEDP). In contrast, a control peptide lacking the redox site did not confer
      cardioprotection. Immunoblot analysis showed that PSELT-dependent
      cardioprotection is accompanied by a significant increase in phosphorylated Akt,
      Erk-1/2 and Gsk3alpha-beta, and a decrement of p38MAPK. PSELT inhibited the pro
      apoptotic factors Bax, caspase 3 and cytochrome c and stimulated the anti
      apoptotic factor Bcl-2. Furthermore, PSELT significantly reduced several markers
      of I/R-induced oxidative and nitrosative stress. CONCLUSION: These results
      unravel the role of SelT as a cardiac modulator and identify PSELT as an
      effective pharmacological post-conditioning agent able to protect the heart after
      ischaemic injury.

PMID- 29575759
TI  - Assessment of acute toxicity tests and rhizotron experiments to characterize
      lethal and sublethal control of soil-based pests.
AB  - BACKGROUND: Characterizing lethal and sublethal control of soil-based pests with
      plant protection products is particularly challenging due to the complex and
      dynamic interplay of the system components. Here, we present two types of
      studies: acute toxcity experiments (homogenous exposure of individuals in soil)
      and rhizotron experiments (heterogeneous exposure of individuals in soil) to
      investigate their ability to strengthen our understanding of mechanisms driving
      the effectivness of the plant protection product. Experiments were conducted
      using larvae of the western corn rootworm Diabrotica virgifera LeConte and three
      pesticide active ingredients: clothianidin (neonicotinoid), chlorpyrifos
      (organophosphate) and tefluthrin (pyrethroid). RESULTS: The order of compound
      concentrations needed to invoke a specific effect intensity (EC50 values) within
      the acute toxicity tests was chlorpyrifos > tefluthrin > clothianidin. This order
      changed for the rhizotron experiments because application type, fate and
      transport of the compounds in the soil profile, and sublethal effects on larvae
      also influence their effectiveness in controlling larval feeding on corn roots.
      CONCLUSION: Beyond the pure measurement of efficacy through observing relative
      changes in plant injury to control plants, the tests generate mechanistic
      understanding for drivers of efficacy apart from acute toxicity. The experiments
      have the potential to enhance efficacy testing and product development, and might
      be useful tools for assessing resistance development in the future. (c) 2018
      Society of Chemical Industry.

PMID- 29575761
TI  - Osteomalacia Due to Drug-Induced Fanconi Syndrome.

PMID- 29575760
TI  - Analysis of the activity and safety of weekly low-dose bevacizumab-based regimens
      in heavily pretreated patients with metastatic breast cancer.
AB  - BACKGROUND: Currently, there are no standard regimens for metastatic breast
      cancer patients (MBC) who have failed >= 3 chemotherapy treatments. The aim of
      this study was to assess whether weekly low-dose bevacizumab-based regimens were
      well tolerated and would improve efficacy in MBC patients who had failed numerous
      therapies. METHODS: Seventeen patients with MBC who were heavily pretreated with
      a median of five regimens of therapy (range 1-10) between 2012 and 2016 were
      included in the analysis. Bevacizumab was administered at a dose of 100 mg
      intravenously once a week combined with one or two types of chemotherapeutic
      drugs until confirmed disease progression or an intolerable adverse event was
      observed. Patient characteristics, objective response rate, clinical benefit
      rate, progression-free survival, and toxicity were assessed. RESULTS: All 17
      patients had been pretreated with taxane-based and anthracycline-based
      chemotherapy. Weekly low-dose bevacizumab combined with one or two types of
      chemotherapeutic drugs, which had usually not been previously used (e.g.
      etoposide, irinotecan, pemetrexed, methotrexate, and nab-paclitaxel), was
      administered. Three patients achieved a partial response, while one had stable
      disease for > 24 weeks, and the clinical benefit rate was 23.5%. Median
      progression-free survival was 3.4 months (95% confidence interval 2.0-4.8). The
      most common hematological adverse events were neutropenia, anemia, and
      thrombocytopenia. Bevacizumab-related adverse events included grade 1 bleeding
      (17.6%) and grade 2 hypertension (5.9%). CONCLUSIONS: Weekly low-dose bevacizumab
      combined with chemotherapy shows a relatively favorable clinical response and
      tolerable toxicity, providing a feasible option for heavily pretreated MBC
      patients.

PMID- 29575762
TI  - Fresh spring air for Andrology.

PMID- 29575764
TI  - An increase in salivary flow with amitriptyline may indicate treatment resistance
      in burning mouth syndrome.

PMID- 29575763
TI  - DNA methylation profiling reveals a pathological signature that contributes to
      transcriptional defects of CD34+ CD15- cells in early chronic-phase chronic
      myeloid leukemia.
AB  - Despite the high efficiency of tyrosine kinase inhibitors (TKI), some patients
      with chronic myeloid leukemia (CML) will display residual disease that can become
      resistant to treatment, indicating intraclonal heterogeneity in chronic-phase CML
      (CP-CML). To determine the basis of this heterogeneity, we conducted the first
      exhaustive characterization of the DNA methylation pattern of sorted CP-CML CD34+
      CD15- (immature) and CD34- CD15+ (mature) cells at diagnosis (prior to any
      treatment) and compared it to that of CD34+ CD15- and CD34- CD15+ cells isolated
      from healthy donors (HD). In both cell types, we identified several hundreds of
      differentially methylated regions (DMRs) showing DNA methylation changes between
      CP-CML and HD samples, with only a subset of them in common between CD34+ CD15-
      and CD34- CD15+ cells. This suggested DNA methylation variability within the same
      CML clone. We also identified 70 genes that could be aberrantly repressed upon
      hypermethylation and 171 genes that could be aberrantly expressed upon
      hypomethylation of some of these DMRs in CP-CML cells, among which 18 and 81,
      respectively, were in CP-CML CD34+ CD15- cells only. We then validated the DNA
      methylation and expression defects of selected candidate genes. Specifically, we
      identified GAS2, a candidate oncogene, as a new example of gene the
      hypomethylation of which is associated with robust overexpression in CP-CML
      cells. Altogether, we demonstrated that DNA methylation abnormalities exist at
      early stages of CML and can affect the transcriptional landscape of malignant
      cells. These observations could lead to the development of combination treatments
      with epigenetic drugs and TKI for CP-CML.

PMID- 29575765
TI  - Combination therapy of apatinib with icotinib for primary acquired icotinib
      resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.
AB  - Multi-targeted agents represent the next generation of targeted therapies for
      solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase
      inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third
      generation targeted drugs, such as osimertinib, are very expensive, thus a more
      economical solution is required. The aim of this study was to explore the use of
      apatinib combined with icotinib therapy for primary acquired resistance to
      icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR
      mutations. We achieved favorable oncologic outcomes in all three patients, with
      progression-free survival of four to six months. Unfortunately, the patients
      ultimately had to cease combination therapy because of intolerable adverse
      effects of hand and foot syndrome and oral ulcers. Combination therapy of
      apatinib with icotinib for primary acquired resistance to icotinib may be an
      option for patients with advanced pulmonary adenocarcinoma with EGFR mutations,
      but physicians must also be aware of the side effects caused by such therapy.

PMID- 29575766
TI  - Pseudoaneurysm of the left main coronary artery: A complication of orbital
      atherectomy.
AB  - Plaque modification devices are used to treat heavily calcified coronary artery
      lesions during percutaneous coronary artery interventions. As these devices have
      unique risk profiles, clinicians need to be aware of potential complications
      associated with their use. A case of a contained rupture (i.e., pseudoaneurysm)
      of the proximal left main coronary artery following orbital atherectomy is
      presented. This lesion was managed with coronary artery bypass grafting and
      oversewing of the left main coronary artery ostium. This case illustrates that
      lesion location and configuration may influence tracking of these devices, as
      well as the actual site of tissue ablation. This case underscores the importance
      of concurrent imaging during treatment and concern for potential unintended
      consequences of atherectomy.

PMID- 29575767
TI  - Structure and Bonding in CE5- (E=Al-Tl) Clusters: Planar Tetracoordinate Carbon
      versus Pentacoordinate Carbon.
AB  - The structure, bonding, and stability of clusters with the empirical formula CE5-
      (E=Al-Tl) have been analyzed by means of high-level computations. The results
      indicate that, whereas aluminum and gallium clusters have C2v structures with a
      planar tetracoordinate carbon (ptC), their heavier homologues prefer three
      dimensional C4v forms with a pentacoordinate carbon center over the ptC one. The
      reason for such a preference is a delicate balance between the interaction energy
      of the fifth E atom with CE4 and the distortion energy. Moreover, bonding
      analysis shows that the ptC systems can be better described as CE4- , with 17
      valence electrons interacting with E. The ptC core in these systems exhibits
      double aromatic (both sigma and pi) behavior, but the sigma contribution is
      dominating.

PMID- 29575768
TI  - Hepatitis A Virus in men who have sex with men: Need for awareness and
      vaccination.

PMID- 29575769
TI  - Expanding our toolkit to better identify drug-induced liver injury in electronic
      medical records.

PMID- 29575770
TI  - Assessment of Relative Bioavailability of Moroctocog Alfa and Moroctocog Alfa (AF
      CC) in Subjects With Severe Hemophilia A.
AB  - : An open-label, single-dose, randomized, two-period, crossover study comparing
      the pharmacokinetics of factor VIII activity in plasma (FVIII:C) after
      administration of an albumin-free presentation of moroctocog alfa (test) and
      moroctocog alfa manufactured using the previous technique (reference) was
      conducted in 30 (25 evaluable) male subjects who had severe hemophilia A (FVIII:C
      < 1 IU/dL). Blood samples were collected for 48 h after administration of each
      dose. FVIII: C was assayed using a chromogenic substrate assay. The FVIII:C
      pharmacokinetic parameters were calculated using noncompartmental analysis. The
      presentations would be bioequivalent if the 90% confidence limits of the ratio of
      the geometric mean values of AUCinf and recovery fell within the interval of 80
      125%. The bioequivalence criteria were met. A total of 10 treatment-related
      adverse events were observed in a total of nine subjects. All were mild and none
      was determined to be related to administration of study medication.

PMID- 29575772
TI  - LncRNA SNHG1 functions as a ceRNA to antagonize the effect of miR-145a-5p on the
      down-regulation of NUAK1 in nasopharyngeal carcinoma cell.
AB  - How lncRNA SNHG1 influences the aggressiveness of nasopharyngeal carcinoma cells
      as well as the underlying mechanism was studied. The lncRNA differences were
      analysed by GSE12452 gene microarray. The expression of SNHG1, MiR-145-5p and
      NUAK1 was identified by qRT-PCR and western blot. Transfection was conducted to
      construct nasopharyngeal carcinoma cells with different expressions of SNHG1, miR
      145-5p and NUAK1. Dual-luciferase reporter assay was performed to explore the
      relationship between SNHG1, miR-145-5p and NUAK1. Wound-healing assay and
      transwell invasion experiments were employed to study changes in cell migration
      capacity and cell invasion, respectively. Tumour xenografts were performed to
      observe lung metastasis of nude mice inoculated with transfected CNE cells. SNHG1
      is highly expressed in nasopharyngeal carcinoma tissues and in cell lines. Down
      regulation of SNHG1 facilitated the expression of miR-145-5p and further
      suppressed the level of NAUK1 in CNE and HNE-1 cells. Silencing of SNHG1, up
      regulation of miR-145-5p and inhibition of NAUK1 by relative transfection all
      attenuated the aggressiveness of CNE and HNE-1 cells both in vivo and in vitro.
      Moreover, the impaired cell migration and invasion by SNHG1 siRNA could be
      rescued by cotransfection of miR-145-5p in CNE and HNE-1 cells. LncRNA SNHG1
      promoted the expression of NUAK1 by down-regulating miR-145-5p and thus promoted
      the aggressiveness of nasopharyngeal carcinoma cells through AKT signalling
      pathway and induced epithelial-mesenchymal transition (EMT).

PMID- 29575771
TI  - The habenula as a novel link between the homeostatic and hedonic pathways in
      cancer-associated weight loss: a pilot study.
AB  - BACKGROUND: Little is known about the brain mechanisms underlying cancer
      associated weight loss (C-WL) in humans despite this condition negatively
      affecting their quality of life and survival. We tested the hypothesis that
      patients with C-WL have abnormal connectivity in homeostatic and hedonic brain
      pathways together with altered brain activity during food reward. METHODS: In 12
      patients with cancer and 12 healthy controls, resting-state functional
      connectivity (RSFC, resting brain activity observed through changes in blood flow
      in the brain which creates a blood oxygen level-dependent signal that can be
      measured using functional magnetic resonance imaging) was used to compare three
      brain regions hypothesized to play a role in C-WL: the hypothalamus
      (homeostatic), the nucleus accumbens (hedonic), and the habenula (an important
      regulator of reward). In addition, the brain reward response to juice was
      studied. Participants included 12 patients with histological diagnosis of
      incurable cancer (solid tumours), a European Cooperative Oncology Group
      performance status of 0-2, and a >=5% involuntary body weight loss from pre
      illness over the previous 6 months and 12 non-cancer controls matched for age,
      sex, and race. RSFC between the hypothalamus, nucleus accumbens, and habenula and
      brain striatum activity as measured by functional MRI during juice reward
      delivery events were the main outcome measures. RESULTS: After adjusting for BMI
      and compared with matched controls, patients with C-WL were found to have reduced
      RSFC between the habenula and hypothalamus (P = 0.04) and between the habenula
      and nucleus accumbens (P = 0.014). Patients with C-WL also had reduced juice
      reward responses in the striatum compared with controls. CONCLUSIONS: In patients
      with C-WL, reduced connectivity between both homeostatic and hedonic brain
      regions and the habenula and reduced juice reward were observed. Further research
      is needed to establish the relevance of the habenula and striatum in C-WL.

PMID- 29575773
TI  - Non-invasive ventilation practices in children across Europe.
AB  - OBJECTIVES: To describe the diversity in practice in non-invasive ventilation
      (NIV) in European pediatric intensive care units (PICUs). WORKING HYPOTHESIS: No
      information about the use of NIV in Pediatrics across Europe is currently
      available, and there might be a wide variability regarding the approach. STUDY
      DESIGN: Cross-sectional electronic survey. METHODOLOGY: The survey was
      distributed to the ESPNIC mailing list and to researchers in different European
      centers. RESULTS: One hundred one units from 23 countries participated. All
      respondent units used NIV. Almost all PICUs considered NIV as initial respiratory
      support (99.1%), after extubation (95.5% prophylactically, 99.1%
      therapeutically), and 77.5% as part of palliative care. Overall NIV use outside
      the PICUs was 15.5% on the ward, 20% in the emergency department, and 36.4%
      during transport. Regarding respiratory failure cause, NIV was delivered in
      pneumonia (97.3%), bronchiolitis (94.6%), bronchospasm (75.2%), acute pulmonary
      edema (84.1%), upper airway obstruction (76.1%), and in acute respiratory
      distress syndrome (91% if mild, 53.1% if moderate, and 5.3% if severe). NIV use
      in asthma was less frequent in Northern European units in comparison to Central
      and Southern European PICUs (P = 0.007). Only 47.7% of the participants had a
      written protocol about NIV use. Bilevel NIV was applied mostly through an
      oronasal mask (44.4%), and continuous positive airway pressure through nasal
      cannulae (39.8%). If bilevel NIV was required, 62.3% reported choosing pressure
      support (vs assisted pressure-controlled ventilation) in infants; and 74.5% in
      older children. CONCLUSIONS: The present study shows that NIV is a widespread
      technique in European PICUs. Practice across Europe is variable.

PMID- 29575774
TI  - Silk fibroin enhances peripheral nerve regeneration by improving vascularization
      within nerve conduits.
AB  - Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral
      nerve defects. Our previous study showed that nerve regeneration in a SF-blended
      poly (l-lactide-co-E-caprolactone) [P(LLA-CL)] nerve conduit is better than that
      in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified.
      Because angiogenesis within a nerve conduit plays an important role in nerve
      regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared
      both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL)
      nanofibers significantly promoted fibroblast proliferation, and vascular
      endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL)
      nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers.
      Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human
      umbilical vein endothelial cells (HUVEC) to form capillary-like networks and
      promoted faster HUVEC migration. The two kinds of nerve conduits were used to
      bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood
      vessel area in the SF/P(LLA-CL) group was significantly larger than that in the
      P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in
      the SF/P(LLA-CL) group, which was consistent with the results of blood vessels.
      Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances
      peripheral nerve regeneration by improving angiogenesis within the conduit. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018.

PMID- 29575775
TI  - Recurrent reciprocal copy number variants: Roles and rules in neurodevelopmental
      disorders.
AB  - Deletions and duplications, called reciprocal CNVs when they occur at the same
      locus, are implicated in neurodevelopmental phenotypes ranging from morphological
      to behavioral. In this article, we propose three models of how differences in
      gene expression in deletion and duplication genotypes may result in deleterious
      phenotypes. To explore these models, we use examples of the similarities and
      differences in clinical phenotypes of five reciprocal CNVs known to cause
      neurodevelopmental disorders: 1q21.1, 7q11.23, 15q13.3, 16p11.2, and 22q11.2.
      These models and examples may inform some insights into better understanding of
      gene-phenotype relationships. (c) 2018 Wiley Periodicals, Inc. Develop Neurobiol
      78: 519-530, 2018.

PMID- 29575776
TI  - Quantitative Analysis of Multiple Proteins of Different Invasive Tumor Cell Lines
      at the Same Single-Cell Level.
AB  - Tumor cell invasion is pivotal to the development, metastasis, and prognosis of
      tumors. It is reported that the invasive ability of tumor cells is mainly
      dependent on the expression levels of membrane type-1 matrix metalloproteinase
      (MT1-MMP) and integrin alphaV beta3 proteins on cell membranes. To precisely
      distinguish between tumor cells with different invasive abilities, it is
      important to establish a highly sensitive and precise quantification method to
      differentiate the expression levels of MT1-MMP and integrin alphaV beta3 in the
      same single tumor cell at the same time. Herein, two functional peptides to
      construct red-emissive Au26 clusters and green-emissive Ag12 clusters are
      reported. Moreover, the Au26 clusters and Ag12 clusters have the ability to
      specifically target MT1-MMP and integrin alphaV beta3 , respectively, in the same
      single cell at the same time. By utilizing the fluorescent properties and
      metallic compositions of metal clusters, the MT1-MMP and integrin alphaV beta3
      levels of the more invasive SiHa cells or the less invasive HeLa cells are
      simultaneously and quantitatively differentiated via laser ablation inductively
      coupled plasma mass spectrometry. This method of quantitatively detecting
      multiple invasive proteins on the same cell is of great value for accurately
      diagnosing aggressive tumors and monitoring the invasiveness of these tumors.

PMID- 29575777
TI  - Phylogeography of Diaphorina citri (Hemiptera: Liviidae) and its primary
      endosymbiont, 'Candidatus Carsonella ruddii': an evolutionary approach to host
      endosymbiont interaction.
AB  - BACKGROUND: In insects, little is known about the co-evolution between their
      primary endosymbionts and hosts at the intraspecific level. This study examined
      co-diversification between the notorious agricultural pest Diaphorina citri and
      its primary endosymbionts (P-endosymbiont), 'Candidatus Carsonella ruddii' at the
      population level. RESULTS: Maximum likelihood, haplotype network, principal
      components and Bayesian clustering identified three lineages for D. citri and its
      P-endosymbiont: a Western clade containing individuals from Pakistan, Bhutan
      (Phuentsholing), Vietnam (Son La), USA, Myanmar and China (Ruili, Yunnan); a
      Central clade, with accessions originating from Southwest China, Bhutan (Tsirang)
      and Bangladesh; and an Eastern clade containing individuals from Southeast Asia,
      and East and South China. A more diverse genetic structure was apparent in the
      host mitochondrial DNA than their P-endosymbionts; however, the two sets of data
      were strongly congruent. CONCLUSION: This study provides evidence for the co
      diversification of D. citri and its P-endosymbiont during the migration from
      South Asia to East and Southeast Asia. We also suggest that the P-endosymbiont
      may facilitate investigations into the genealogy and migration history of the
      host. The biogeography of D. citri and its P-endosymbiont indicated that D. citri
      colonized and underwent a secondary dispersal from South Asia to East and
      Southeast Asia. (c) 2018 Society of Chemical Industry.

PMID- 29575778
TI  - Signal transducer and activator of transcription 3 overexpression promotes lymph
      node micrometastasis in early-stage non-small cell lung cancer.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is
      constitutively activated in several malignancies. Here, we define the correlation
      between STAT3 expression and lymph node micrometastasis of early-stage non-small
      cell lung cancer. Then we highlight some possibilities associated with developing
      a way to detect tumor micrometastasis and an anticancer drug that might
      therapeutically inhibit the STAT3 signaling pathway. METHODS: The samples were
      collected from 50 patients with early-stage non-small cell lung cancer and 50
      patients with benign lung tumors. Mucin 1 mRNA expression was evaluated to
      determine lymph node micrometastasis status. STAT3 mRNA, STAT3 protein, and
      phosphorylated STAT3 protein expression were evaluated through reverse
      transcription polymerase chain reaction, western blot, and immunohistochemistry,
      respectively. Measurement data was represented as mean +/- standard deviation,
      and the t-rest or F-test were used. The chi2 -test was used in enumeration data.
      Logistic regression analysis was carried out to determine the independent risk
      factors influencing lymph node micrometastasis. RESULTS: STAT3 mRNA and proteins
      expression were correlated with lymph node micrometastasis (P < 0.05). Logistic
      regression analysis revealed STAT3 protein overexpression and the differentiation
      degree of tumors were independent risk factors for lymph node micrometastasis.
      CONCLUSION: Overexpression of STAT3 might promote lymphatic micrometastasis of
      early-stage non-small cell lung cancer and might be a clinical predictor of lymph
      node micrometastasis.

PMID- 29575779
TI  - Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures:
      Environmental Domain.
AB  - BACKGROUND: There is growing interest in how environment is related to adults'
      weight and activity and eating behaviors. However, little is known about whether
      environmental factors are related to the individual variability seen in adults'
      intentional weight loss or maintenance outcomes. OBJECTIVES: The environmental
      domain subgroup of the Accumulating Data to Optimally Predict obesity Treatment
      (ADOPT) Core Measures Project sought to identify a parsimonious set of objective
      and perceived neighborhood and social environment constructs and corresponding
      measures to include in the assessment of response to adult weight-loss treatment.
      SIGNIFICANCE: Starting with the home address, the environmental domain subgroup
      recommended for inclusion in future weight-loss or maintenance studies constructs
      and measures related to walkability, perceived land use mix, food outlet
      accessibility (perceived and objective), perceived food availability,
      socioeconomics, and crime-related safety (perceived and objective) to
      characterize the home neighborhood environment. The subgroup also recommended
      constructs and measures related to social norms (perceived and objective) and
      perceived support to characterize an individual's social environment. The 12
      neighborhood and social environment constructs and corresponding measures provide
      a succinct and comprehensive set to allow for more systematic examination of the
      impact of environment on adults' weight loss and maintenance.

PMID- 29575780
TI  - The Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core
      Measures Project: Rationale and Approach.
AB  - BACKGROUND: Individual variability in response to multiple modalities of obesity
      treatment is well documented, yet our understanding of why some individuals
      respond while others do not is limited. The etiology of this variability is
      multifactorial; however, at present, we lack a comprehensive evidence base to
      identify which factors or combination of factors influence treatment response.
      OBJECTIVES: This paper provides an overview and rationale of the Accumulating
      Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, which
      aims to advance the understanding of individual variability in response to adult
      obesity treatment. This project provides an integrated model for how factors in
      the behavioral, biological, environmental, and psychosocial domains may influence
      obesity treatment responses and identify a core set of measures to be used
      consistently across adult weight-loss trials. This paper provides the foundation
      for four companion papers that describe the core measures in detail.
      SIGNIFICANCE: The accumulation of data on factors across the four ADOPT domains
      can inform the design and delivery of effective, tailored obesity treatments.
      ADOPT provides a framework for how obesity researchers can collectively generate
      this evidence base and is a first step in an ongoing process that can be refined
      as the science advances.

PMID- 29575781
TI  - Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures:
      Psychosocial Domain.
AB  - BACKGROUND: Within the Accumulating Data to Optimally Predict obesity Treatment
      (ADOPT) Core Measures Project, the psychosocial domain addresses how psychosocial
      processes underlie the influence of obesity treatment strategies on weight loss
      and weight maintenance. The subgroup for the psychosocial domain identified an
      initial list of high-priority constructs and measures that ranged from relatively
      stable characteristics about the person (cognitive function, personality) to
      dynamic characteristics that may change over time (motivation, affect).
      OBJECTIVES: This paper describes (a) how the psychosocial domain fits into the
      broader model of weight loss and weight maintenance as conceptualized by ADOPT;
      (b) the guiding principles used to select constructs and measures for
      recommendation; (c) the high-priority constructs recommended for inclusion; (d)
      domain-specific issues for advancing the science; and (e) recommendations for
      future research. SIGNIFICANCE: The inclusion of similar measures across trials
      will help to better identify how psychosocial factors mediate and moderate the
      weight loss and weight maintenance process, facilitate research into dynamic
      interactions with factors in the other ADOPT domains, and ultimately improve the
      design and delivery of effective interventions.

PMID- 29575783
TI  - ADOPT: Obesity Treatment Reaches Level of Maturity with Its Own Collaborative
      Initiative and Resource.

PMID- 29575782
TI  - Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures:
      Behavioral Domain.
AB  - BACKGROUND: The ability to identify and measure behaviors that are related to
      weight loss and the prevention of weight regain is crucial to understanding the
      variability in response to obesity treatment and the development of tailored
      treatments. OBJECTIVES: The overarching goal of the Accumulating Data to
      Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide
      obesity researchers with guidance on a set of constructs and measures that are
      related to weight control and that span and integrate obesity-related behavioral,
      biological, environmental, and psychosocial domains. This article describes how
      the behavioral domain subgroup identified the initial list of high-priority
      constructs and measures to be included, and it describes practical considerations
      for assessing the following four behavioral areas: eating, activity, sleep, and
      self-monitoring of weight. Challenges and considerations for advancing the
      science related to weight loss and maintenance behaviors are also discussed.
      SIGNIFICANCE: Assessing a set of core behavioral measures in combination with
      those from other ADOPT domains is critical to improve our understanding of
      individual variability in response to adult obesity treatment. The selection of
      behavioral measures is based on the current science, although there continues to
      be much work needed in this field.

PMID- 29575784
TI  - Accumulating Data to Optimally Predict Obesity Treatment (ADOPT): Recommendations
      from the Biological Domain.
AB  - BACKGROUND: The responses to behavioral, pharmacological, or surgical obesity
      treatments are highly individualized. The Accumulating Data to Optimally Predict
      obesity Treatment (ADOPT) project provides a framework for how obesity
      researchers, working collectively, can generate the evidence base needed to guide
      the development of tailored, and potentially more effective, strategies for
      obesity treatment. OBJECTIVES: The objective of the ADOPT biological domain
      subgroup is to create a list of high-priority biological measures for weight-loss
      studies that will advance the understanding of individual variability in response
      to adult obesity treatments. This list includes measures of body composition,
      energy homeostasis (energy intake and output), brain structure and function, and
      biomarkers, as well as biobanking procedures, which could feasibly be included in
      most, if not all, studies of obesity treatment. The recommended high-priority
      measures are selected to balance needs for sensitivity, specificity, and/or
      comprehensiveness with feasibility to achieve a commonality of usage and increase
      the breadth and impact of obesity research. SIGNIFICANCE: The accumulation of
      data on key biological factors, along with behavioral, psychosocial, and
      environmental factors, can generate a more precise description of the interplay
      and synergy among them and their impact on treatment responses, which can
      ultimately inform the design and delivery of effective, tailored obesity
      treatments.

PMID- 29575785
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli in common vampire
      bats Desmodus rotundus and livestock in Peru.
AB  - Antibiotic resistance mediated by bacterial production of extended-spectrum beta
      lactamase (ESBL) is a global threat to public health. ESBL resistance is most
      commonly hospital-acquired; however, infections acquired outside of hospital
      settings have raised concerns over the role of livestock and wildlife in the
      zoonotic spread of ESBL-producing bacteria. Only limited data are available on
      the circulation of ESBL-producing bacteria in animals. Here, we report ESBL
      producing Escherichia coli in wild common vampire bats Desmodus rotundus and
      livestock near Lima, Peru. Molecular analyses revealed that most of this
      resistance resulted from the expression of blaCTX-M-15 genes carried by plasmids,
      which are disseminating worldwide in hospital settings and have also been
      observed in healthy children of Peru. Multilocus sequence typing showed a diverse
      pool of E. coli strains carrying this resistance that were not always host
      species-specific, suggesting sharing of strains between species or infection from
      a common source. This study shows widespread ESBL resistance in wild and domestic
      animals, supporting animal communities as a potential source of resistance.
      Future work is needed to elucidate the role of bats in the dissemination of
      antibiotic-resistant strains of public health importance and to understand the
      origin of the observed resistance.

PMID- 29575787
TI  - Sequential Coating of Insulin Secreting Beta Cells within Multilayers of
      Polysaccharide Nanogels.
AB  - Pancreatic islet transplantation has emerged as a promising treatment for type-1
      diabetes (T1D); however, its clinical application is still limited by the life
      long use of immunosuppressive drugs, insufficient number of islets to achieve
      normoglycemia, and large transplantation volume. This paper reports a unique
      approach for nanothin coating of insulin secreting beta cell aggregates. The
      coating is based on hydrophobic and covalent interactions between natural
      acrylate modified cholesterol bearing pullulan (CHPOA) nanogels and MIN6 beta
      cell aggregates. Beta cell aggregates are prepared as spheroids through hanging
      drop method, which is optimized with respect to hanging drop volume and initial
      number of beta cells. These aggregates, defined as pseudoislets, are coated with
      sequential layers of nanogels and are evaluated as viable and functional for
      insulin secretion. Coating experiments are carried out using physiologically
      compatible medium, where pseudoislets are not brought in contact with toxic
      prepolymer solutions used in existing approaches. This study offers new
      opportunities through coating of islets with advanced functional materials under
      completely physiological conditions for clinical translation of cell
      transplantation technology. The technique developed here will establish a new
      paradigm for creating tolerable grafts for other chronic diseases such as anemia,
      cancer, central nervous system (CNS) diseases.

PMID- 29575786
TI  - Lactation and progression to type 2 diabetes in patients with gestational
      diabetes mellitus: A systematic review and meta-analysis of cohort studies.
AB  - AIMS/INTRODUCTION: To explore the association between lactation and type 2
      diabetes incidence in women with prior gestational diabetes. MATERIALS AND
      METHODS: We searched PubMed, Embase and the Cochrane Library for cohort studies
      published through 12 June 2017 that evaluated the effect of lactation on the
      development of type 2 diabetes in women with prior gestational diabetes. A random
      effects model was used to estimate relative risks (RRs) with 95% confidence
      intervals (CIs). RESULTS: A total of 13 cohort studies were included in the meta
      analysis. The pooled result suggested that compared with no lactation, lactation
      was significantly associated with a lower risk of type 2 diabetes (RR 0.66, 95%
      CI 0.48-0.90, I2  = 72.8%, P < 0.001). This relationship was prominent in a study
      carried out in the USA (RR 0.66, 95% CI 0.43-0.99), regardless of study design
      (prospective design RR 0.56, 95% CI 0.41-0.76; retrospective design RR 0.63, 95%
      CI 0.40-0.99), smaller sample size (RR 0.52, 95% CI 0.30-0.92, P = 0.024) and
      follow-up duration >1 years (RR 0.75, 95% CI 0.56-1.00), and the study used
      adjusted data (RR 0.69, 95% CI 0.50-0.94). Finally, by pooling data from three
      studies, we failed to show that compared with no lactation, long-term lactation
      (>1 to 3 months postpartum) was associated with the type 2 diabetes risk (RR
      0.69, 95% CI 0.41-1.17). CONCLUSIONS: The present meta-analysis showed that
      lactation was associated with a lower risk of type 2 diabetes in women with prior
      gestational diabetes. Furthermore, no significant relationship between long-term
      lactation and type 2 diabetes risk was detected. The impact of long-term
      lactation and the risk of type 2 diabetes should be verified in further large
      scale studies.

PMID- 29575788
TI  - Acute Kidney Injury in Critically Ill Patients: A Prospective Randomized Study of
      Tidal Peritoneal Dialysis Versus Continuous Renal Replacement Therapy.
AB  - Few studies have discussed the role of peritoneal dialysis (PD) in managing acute
      kidney injury (AKI) in critically ill patients. The present study compares the
      outcome of AKI in intensive care unit (ICU) patients randomized to treatment with
      tidal PD (TPD) or continuous venovenous hemodiafiltration (CVVHDF). One hundred
      and twenty-five ICU patients with AKI were randomly allotted to CVVHDF, (Group A,
      N = 62) or TPD, (group B, N = 63). Cause and severity of renal injury were
      assessed at the time of initiating dialysis. The primary outcome was hospital
      mortality at 28 days, and secondary outcomes were time to recovery of renal
      function, duration of stay in the ICU, metabolic and fluid control, and
      improvement of sensorial and hemodynamic parameters. No statistically significant
      differences were observed between groups in regard to patients' characteristics.
      The survival at 28 days was significantly better in the patients treated with TPD
      when compared to CVVHDF (69.8% vs. 46.8%, P < 0.01). Infectious complications
      were significantly less (P < 0.01) in the TPD group (9.5%) when compared to the
      CVVHDF group (17.7%). Recovery of kidney function (60.3% vs. 35.5%), median time
      to resolution of AKI and the median duration of ICU stay of 9 days (7-11) vs. 19
      days (13-20) were all in favor of TPD (P < 0.01). This study suggests that there
      are better outcomes with TPD compared to CRRT in the treatment of critically ill
      patients with AKI.

PMID- 29575789
TI  - Seed Polyphenolic Profile, Antioxidative Activity, and Fatty Acids Composition of
      Wild and Cultivated Carthamus Species.
AB  - Total flavonoid content (TFC) and cyanidin-3-glucoside (Cyd-3-glu) of seed and
      seed coat extract of 16 genotypes from five species of Carthamus were studied,
      and their major polyphenolic compounds and antioxidant activity of the seed coat
      extracts were determined using HPLC analysis and DPPH assay, respectively.
      Additionally, fatty acids composition of the seed oil was analyzed by GC. In
      general, TFC and Cyd-3-glu content of seed coat extracts were higher than those
      of seed extracts. A novel breeding line with black seed coat (named A82) depicted
      lower TFC (3.79 mg QUE/g DW) but higher Cyd-3-glu (24.64 mg/g DW) compared to the
      white and other seed-pigmented genotypes. DPPH radical scavenging activity showed
      a strong association with Cyd-3-glu content (r = 0.84), but no correlation with
      TFC (r = -0.32). HPLC analysis of seed coat extracts revealed that four compounds
      were dominant constituents including rutin (7.23 - 117.95 mg/100 g DW), apigenin
      (4.37 - 64.88 mg/100 g DW), quercetin (3.09 - 14.10 mg/100 g DW), and ferulic
      acid (4.49 - 30.41 mg/100 g DW). Interestingly, the genotype A82 with an
      appropriate polyunsaturated/saturated fatty acids index (5.46%) and a moderate
      linoleic fatty acid content (64.70%) had higher nutritional and pharmaceutical
      value than all the other genotypes.

PMID- 29575790
TI  - Salt induction and activation of MtlD, the key enzyme in the synthesis of the
      compatible solute mannitol in Acinetobacter baumannii.
AB  - Mannitol is the major compatible solute, next to glutamate, synthesized by the
      opportunistic human pathogen Acinetobacter baumannii under low water activities.
      The key enzyme for mannitol biosynthesis, MtlD, was identified. MtlD is highly
      similar to the bifunctional mannitol-1-phosphate dehydrogenase/phosphatase from
      Acinetobacter baylyi. After deletion of the mtlD gene from A. baumannii ATCC
      19606T cells no longer accumulated mannitol and growth was completely impaired at
      high salt. Addition of glycine betaine restored growth, demonstrating that
      mannitol is an important compatible solute in the human pathogen. MtlD was
      heterologously produced and purified. Enzyme activity was strictly salt
      dependent. Highest stimulation was reached at 600 mmol/L NaCl. Addition of
      different sodium as well as potassium salts restored activity, with highest
      stimulations up to 41 U/mg protein by sodium glutamate. In contrast, an increase
      in osmolarity by addition of sugars did not restore activity. Regulation of
      mannitol synthesis was also assayed at the transcriptional level. Reporter gene
      assays revealed that expression of mtlD is strongly dependent on high osmolarity,
      not discriminating between different salts or sugars. The presence of glycine
      betaine or its precursor choline repressed promoter activation. These data
      indicate a dual regulation of mannitol production in A. baumannii, at the
      transcriptional and the enzymatic level, depending on high osmolarity.

PMID- 29575792
TI  - Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with
      mesenchymal stem cells in diabetic wound healing.
AB  - Significantly effective therapies need to be developed for chronic nonhealing
      diabetic wounds. In this work, the topical transplantation of mesenchymal stem
      cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a
      novel therapeutic strategy for diabetic cutaneous wound healing. GFP-labeled MSCs
      were cocultured with an ADM scaffold that was decellularized from normal mouse
      skin. These cultures were subsequently transplanted as a whole into the full
      thickness cutaneous wound site in streptozotocin-induced diabetic mice. Wounds
      treated with MSC-ADM demonstrated an increased percentage of wound closure. The
      treatment of MSC-ADM also greatly increased angiogenesis and rapidly completed
      the reepithelialization of newly formed skin on diabetic mice. More importantly,
      multiphoton microscopy was used for the intravital and dynamic monitoring of
      collagen type I (Col-I) fibers synthesis via second harmonic generation imaging.
      The synthesis of Col-I fibers during diabetic wound healing is of great
      significance for revealing wound repair mechanisms. In addition, the activity of
      GFP-labeled MSCs during wound healing was simultaneously traced via two-photon
      excitation fluorescence imaging. Our research offers a novel advanced nonlinear
      optical imaging method for monitoring the diabetic wound healing process while
      the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds
      seeded with mesenchymal stem cells in diabetic wound healing using multiphoton
      microscopy. PMT, photo-multiplier tube.

PMID- 29575791
TI  - The essential function of CARD9 in diet-induced inflammation and metabolic
      disorders in mice.
AB  - Inflammation and metabolic disorder are common pathophysiological conditions,
      which play a vital role in the development of obesity and type 2 diabetes. The
      purpose of this study was to explore the effects of caspase recruitment domain
      (CARD) 9 in the high fat diet (HFD)-treated mice and attempt to find a molecular
      therapeutic target for obesity development and treatment. Sixteen male CARD9-/-
      and corresponding male WT mice were fed with normal diet or high fat diet,
      respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen
      consumption and heat production of the mice were detected. The CARD9/MAPK pathway
      related gene and protein were determined in insulin-responsive organs using
      Western blotting and quantitative PCR. The results showed that HFD-induced
      insulin resistance and impairment of glucose tolerance were more severe in WT
      mice than that in the CARD9-/- mice. CARD9 absence significantly modified O2
      consumption, CO2 production and heat production. CARD9-/- mice displayed the
      lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both
      HFD- and ND-treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in
      WT mice but not in the CARD9-/- mice. The results indicated that CARD9 absence
      could be a vital protective factor in diet-induced obesity via the CARD9/MAPK
      pathway, which may provide new insights into the development of gene knockout to
      improving diet-induced obesity and metabolism disorder.

PMID- 29575793
TI  - Influence of beverages and surface roughness on the color change of resin
      composites.
AB  - AIM: The aim of the present study was to determine the degree of surface staining
      and roughness of resin composites (RC) after finishing and polishing with
      different methods and immersion in three soft drinks. METHODS: A microhybrid, a
      nanohybrid, and a hybrid composite were selected. The specimens were prepared and
      divided into three groups of 36 after 24 hours, and designated as either
      unpolished or polished using Sof-Lex discs or Enhance point. Each group was
      further divided into three subgroups, immersed in distilled water, coffee, or
      cola for 1 week (N = 12). Color change (?E) was measured by a spectrophotometer
      after each treatment. The ?E was calculated using the following formula: ?E =
      ([?L]2+[?a]2+[?b]2)1/2. Surface roughness (Ra) was measured after 24 hours and 1
      week. To observe the Ra, a scanning electron microscope was used. RESULTS: A
      moderate correlation between Ra and ?E was determined. Only coffee caused
      perceptible ?E. The effect of Ra on staining was statistically significant (P <
      .05), but immersion in solutions for 7 days did not increase the Ra of RC.
      CONCLUSIONS: The highest Ra values were obtained from hybrid RC. The Enhance
      point created the greatest roughness. Coffee was associated with the greatest ?E
      for all materials and polishing methods.

PMID- 29575794
TI  - Morphological and Biochemical Features of Cerebellar Cortex After Exposure to
      Zinc Oxide Nanoparticles: Possible Protective Role of Curcumin.
AB  - Zinc oxide nanoparticles (ZnONPs) are widely used in the last decades. Therefore,
      investigation of its neurotoxic effect is important. This work aimed to
      investigate the potential adverse effects of ZnONPs on rat's cerebellar cortex
      and the possible neuroprotective role of curcumin (Cur). Forty male albino rats
      were randomly divided into four equal groups. Two groups were injected with
      ZnONPs and one group was previously received Cur before ZnONPs. At the end of the
      experiment, cerebellar tissue samples were prepared for histological,
      morphometric, immunohistochemical study, and tissue levels of oxidative stress
      markers and cytokine analysis. cerebellar damage is clearly visible with ZnONPs.
      Degeneration, loss, disorganization of cerebellar neurons was observed.
      Histopathological degeneration of Purkinje and granular cells together with loss
      of Nissl substance, astrocyte gliosis, and affection of cerebellar blood brain
      barrier were detected. Moreover, an apoptotic marker (caspase-3) was
      significantly expressed in Purkinje and granular layers together with elevated
      gene expression of P53 and COX-2 in cerebellar tissue of ZnONPs intoxicated
      group. Astrocyte gliosis and inflammatory markers IL-1, IL-6, and TNF-alpha were
      expressed significantly in ZnONPs intoxicated cerebellum. These changes were
      associated with evidence of cerebellar oxidative stress. Strikingly, treatment
      with Cur together with ZnONPs recorded morphological improvement, with increased
      number of Purkinje cells and decreased caspase +ve cells. These findings were
      confirmed by morphometric and statistical analysis. Cur ameliorates the deterious
      effect of ZnONPs on the cerebellar cortex through its antioxidant, antiapoptotic,
      and anti-inflammatory efficacies. Anat Rec, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29575795
TI  - Synthesis and effect of a new Terbium gibberellic complex on the
      histopathological alteration induced by Gibberellic acid on liver and kidney of
      mice Mus musculus.
AB  - The objective of this study was to synthesize Gibberellic lanthanide complex and
      evaluate its biological activity to reduce the Gibberellic acid toxicity on liver
      and kidney. The new bis(Gibberellic)-nitro-terbium(III) complex was characterized
      by different analytical methods: elemental analyses, UV-Vis, molar ratio,
      fluorescence, FT-IR, and TGA-DTA measurements. Thirty newborns were classified
      into three groups control, Gibberellic acid, and Terbium gibberellic acid
      complex. Livers and kidneys of studied groups proceed for general histology and
      immunohistochemical staining of Cyr61, cytochrome C, and TNFR2. From the
      absorption titration measurements, the binding constants of DNA with Tb(III)
      (GA)2 complex and free ligand were found to be 3.9 * 104 and 2.1 * 103  m-1 ,
      respectively, with the stoichiometry of 1:1. Hypochromism was observed from the
      absorption titration experiment which indicates the intercalation of Tb(III)
      (GA)2 complex between the base pairs of DNA. Gibberellic acid-treated group
      showed alteration in the histological picture of livers and kidneys that
      accompanied with the reduction in the expression of Cyr61, cyt C, and TNFR2. The
      amelioration was observed in Gibberellic acid complex with Terbium group. The
      study concluded that Terbium gibberellic complex is less dangerous effects than
      Gibberellic acid alone.

PMID- 29575796
TI  - Comparison between photostability of Alexa Fluor 448 and Alexa Fluor 647 with
      conventional dyes FITC and APC by flow cytometry.

PMID- 29575797
TI  - Airway cells from protracted bacterial bronchitis and bronchiectasis share
      similar gene expression profiles.
AB  - AIM: Protracted bacterial bronchitis (PBB) is a common cause of prolonged cough
      in young children, and may be a precursor of bronchiectasis. Bacteria are often
      present in the lower airways in both PBB and bronchiectasis and may cause
      persistent infections. However, there is a paucity of information available on
      the pathogenesis of PBB and the factors associated with persistent bacterial
      infection and progression to bronchiectasis. This study hypothesised that lung
      immune cells in recurrent PBB and bronchiectasis differentially express genes
      related to immune cell dysfunction compared to lung immune cells from control
      subjects. METHOD: Cells isolated from bronchoalveolar lavage (adult-control and
      PBB BAL cells) were stimulated with nontypeable Haemophilus influenzae (NTHi),
      and expression of genes involved in various inflammatory pathways was assessed.
      RESULT: NTHi induced production of large amounts of IL-1beta, IL-6, and IL-8 in
      adult-control BAL cells, however BAL cells from PBB airways appeared refractory
      to NTHi stimulation. BAL cells from PBB and bronchiectasis showed differential
      expression of several genes relative to control cells, including CCL20, MARCO,
      CCL24, IL-10, PPAR-gamma, CD200R, TREM2, RelB. Expression of genes involved in
      resolution of inflammation and anti-inflammation response, such as CD200R and IL
      10, was associated with the number of pathogenic bacteria found in the airways.
      CONCLUSION: In summary, we have shown that the expression of genes related to
      macrophage function and resolution of inflammation are similar in PBB and
      bronchiectasis. Lung immune cell dysfunction in PBB and bronchiectasis may
      contribute to poor bacterial clearance and prolonged resolution of inflammation.

PMID- 29575798
TI  - Structural and functional characterisation of multi-copper oxidase CueO from
      lignin-degrading bacterium Ochrobactrum sp. reveal its activity towards lignin
      model compounds and lignosulfonate.
AB  - : The identification of enzymes responsible for oxidation of lignin in lignin
      degrading bacteria is of interest for biotechnological valorization of lignin to
      renewable chemical products. The genome sequences of two lignin-degrading
      bacteria, Ochrobactrum sp., and Paenibacillus sp., contain no B-type DyP
      peroxidases implicated in lignin degradation in other bacteria, but contain
      putative multicopper oxidase genes. Multi-copper oxidase CueO from Ochrobactrum
      sp. was expressed and reconstituted as a recombinant laccase-like enzyme, and
      kinetically characterized. Ochrobactrum CueO shows activity for oxidation of beta
      aryl ether and biphenyl lignin dimer model compounds, generating oxidized dimeric
      products, and shows activity for oxidation of Ca-lignosulfonate, generating
      vanillic acid as a low molecular weight product. The crystal structure of
      Ochrobactrum CueO (OcCueO) has been determined at 1.1 A resolution (PDB: 6EVG),
      showing a four-coordinate mononuclear type I copper center with ligands His495,
      His434 and Cys490 with Met500 as an axial ligand, similar to that of Escherichia
      coli CueO and bacterial azurin proteins, whereas fungal laccase enzymes contain a
      three-coordinate type I copper metal center. A trinuclear type 2/3 copper cluster
      was modeled into the active site, showing similar structure to E. coli CueO and
      fungal laccases, and three solvent channels leading to the active site. Site
      directed mutagenesis was carried out on amino acid residues found in the solvent
      channels, indicating the importance for residues Asp102, Gly103, Arg221, Arg223,
      and Asp462 for catalytic activity. The work identifies a new bacterial
      multicopper enzyme with activity for lignin oxidation, and implicates a role for
      bacterial laccase-like multicopper oxidases in some lignin-degrading bacteria.
      DATABASE: Structural data are available in the PDB under the accession number
      6EVG.

PMID- 29575799
TI  - Sentinel lymph node biopsy in 33 non-melanoma skin cancers of the head and neck:
      A twelve-year experience with long-term follow-up.

PMID- 29575800
TI  - Membrane-Based SDS Depletion Ahead of Peptide and Protein Analysis by Mass
      Spectrometry.
AB  - SDS interferes with both bottom-up and top-down MS analysis, requiring removal
      prior to detection. Filter-aided sample preparation (FASP) is favored for bottom
      up proteomics (BUP) while acetone precipitation is popular for top-down
      proteomics (TDP). We recently demonstrated acetone precipitation in a membrane
      filter cartridge. Alternatively, our automated electrophoretic device, termed
      transmembrane electrophoresis (TME), depletes SDS for both TDP and BUP studies.
      Here TME is compared to these two alternative methods of SDS depletion in both
      BUP and TDP workflows. To do so, a modified FASP method is described applicable
      to the SDS purification and recovery of intact proteins, suitable for LC/MS. All
      three methods reliably deplete >99.8% SDS. TME provide higher sample yields
      (average 90%) than FASP (55%) or acetone precipitation (57%), translating into
      higher total protein identifications (973 vs 877 FASP or 890 acetone) and higher
      spectral matches (2.5 times) per protein. In a top down workflow, each SDS
      depletion method yields high-quality MS spectra for intact proteins. These
      results show each of these membrane-based strategies is capable of depleting SDS
      with high sample recovery and high spectra quality for both BUP and TDP studies.

PMID- 29575801
TI  - Drug abuse screening with exhaled breath and oral fluid in adults with substance
      use disorder.
AB  - In the treatment of substance use disorder, regular laboratory-based testing has
      the dual purpose of monitoring compliance with the prescribed medication and
      abstention from medically non-motivated substances (ie, drug abuse screening).
      The principal specimen for testing is urine, but collection of urine has some
      disadvantages, for example being more time-consuming and more intrusive compared
      to other matrices. There is also the risk of adulteration. This project compared
      exhaled breath and oral fluid as alternative matrices for drug abuse screening in
      patients with substance use disorder. All 51 subjects included in the study were
      enrolled at the Drug Addiction Emergency Unit in Stockholm. Exhaled breath, oral
      fluid, and urine samples were collected together with a self-report. Of all 117
      self-reported drug intakes during the previous week, 72% were confirmed in urine,
      73% in oral fluid and 39% in exhaled breath. In 31% of the subjects, additional
      substances other than those self-reported were detected analytically. For
      substance abuse screening, urine had the highest detection rate for
      buprenorphine, cannabis, and benzodiazepines, while oral fluid had the highest
      detection rate for amphetamines and methadone. Exhaled breath showed the highest
      detection rate of all matrices for cocaine. To identify significant differences
      in detection rates between the matrices future studies with larger sampling sizes
      are needed. Both oral fluid and exhaled breath are viable alternative specimens
      to urine, depending on the circumstances and purpose of the testing.

PMID- 29575802
TI  - Diuretic dosing in heart failure: more data are needed.

PMID- 29575803
TI  - Sustained Response Following Discontinuation of Methotrexate in Patients With
      Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab: Results From a
      Randomized, Controlled Trial.
AB  - OBJECTIVE: To evaluate whether tocilizumab (TCZ) monotherapy is noninferior to
      treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in
      patients with rheumatoid arthritis (RA) in whom low disease activity is achieved
      with TCZ plus MTX. METHODS: Patients with RA who experienced an inadequate
      response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks,
      patients who achieved a Disease Activity Score in 28 joints using the erythrocyte
      sedimentation rate (DAS28-ESR) of <=3.2 were randomized to receive TCZ
      monotherapy or to continue treatment with TCZ plus MTX until week 52. The primary
      outcome measure was the comparison of the mean change in the DAS28-ESR from week
      24 to week 40 between the TCZ monotherapy and TCZ plus MTX arms (noninferiority
      margin of 0.6). Secondary outcome measures included worsening of the DAS28-ESR by
      >=1.2, achievement of a DAS28-ESR of <2.6 and <=3.2, and safety and
      immunogenicity. RESULTS: Among the 718 patients enrolled, 296 were randomized at
      week 24 to receive TCZ monotherapy (n = 147) or TCZ plus MTX (n = 147). The mean
      changes in the DAS28-ESR from week 24 to week 40 were 0.46 and 0.14 in the TCZ
      monotherapy arm and the TCZ plus MTX arm, respectively (weighted difference
      between the groups, 0.318 [95% confidence interval 0.045, 0.592]); discontinuing
      MTX in TCZ responders was noninferior to continuing MTX. Safety events were
      broadly similar between the randomized treatment groups; the most common serious
      adverse event was infection, which occurred in 2.1% of patients in the TCZ
      monotherapy group and 2.2% of patients receiving TCZ plus MTX. CONCLUSION:
      Patients with RA receiving TCZ plus MTX who achieve low disease activity can
      discontinue MTX without significant worsening of disease activity during the 16
      weeks following MTX discontinuation.

PMID- 29575804
TI  - Clinical and functional correlates of financially deprived women with first
      episode psychosis.
AB  - BACKGROUND: Women, especially those with low-socio-economic status and financial
      deprivation, are found to be affected by mental illnesses disproportionately. We
      compared the clinical, functioning and cognitive characteristics between the
      financially deprived women with first-episode psychosis and their non-deprived
      women counterparts. METHOD: A cross-sectional analysis of consecutively recruited
      first-episode psychosis women patients was conducted. A total of 93 financially
      deprived women patients and 105 non-deprived women patients aged 25 to 55 years
      were compared in terms of demographic, premorbid and help-seeking
      characteristics, baseline clinical characteristics, baseline functioning and
      baseline cognitive functioning. RESULTS: Financially deprived women were older (P
      = .005), had received less education (P = .001), more likely to live alone (P <
      .001) and with a higher proportion of immigrants (P = .001). Whereas there was no
      significant difference found in duration of untreated psychosis, deprived women
      had more severe depressive symptoms (P = .021) and more severe negative symptoms,
      in terms of avolition-apathy (P = .003) and anhedonia-asociality (P = .008). They
      also perform worse in social and occupational functioning (P = .002) and a range
      of cognitive abilities. CONCLUSIONS: Nearly half of the adult female patients
      with first-episode psychosis in Hong Kong encountered persistent financially
      difficulties. The fact that they suffer from more severe symptoms and worsened
      functioning and cognitive abilities at an early stage of illness shows that this
      subgroup of patients warrant assistance and attention.

PMID- 29575805
TI  - Optic disc-fovea distance and myopia progression in school children: the Beijing
      Children Eye Study.
AB  - PURPOSE: To assess changes in the optic disc-fovea distance (DFD) with
      progressing myopia in school children. METHODS: The school-based, prospective,
      longitudinal study included grade-1 children in 2011 who were yearly re-examined
      until 2016. We measured DFD, optic disc diameters and width of parapapillary
      gamma zone (parapapillary region without Bruch's membrane (BM)) on fundus
      photographs. RESULTS: Of 382 grade-1 children examined in 2011, 294 (77.0%)
      children (mean age in 2011: 6.4 +/- 0.5 years) returned to be examined in 2016.
      In relative terms, the increase in DFD (1.15 +/- 0.33 mm) was more due to an
      increase in gamma zone width (+300% or 0.29 +/- 0.30 mm) than an increase in
      macular BM length (+18% or 0.74 +/- 0.21 mm). In multivariate regression
      analysis, longer increase in DFD was correlated (regression coefficient r2  =
      0.79) with longer axial elongation during the study period (p < 0.001;
      standardized regression coefficient beta: 0.61; non-standardized regression
      coefficient B: 0.30; 95% confidence interval (CI): 0.26, 0.33), larger increase
      in gamma zone width (p < 0.001; beta: 0.35; B: 0.40; 95%CI: 0.32, 0.48) and
      longer axial length in 2011 (p = 0.01; beta:0.07; B:0.03; 95%CI:0.01, 0.06).
      Larger increase in gamma zone width was associated (r2  = 0.73) with larger
      increase in DFD (p < 0.001; beta: 0.51; B: 0.46; 95%CI: 0.39, 0.53), larger
      increase in the vertical-to-horizontal disc diameter ratio (p < 0.001; beta:
      0.43; B:1.21; 95%CI: 1.00, 1.42) and longer vertical disc diameter (p < 0.001;
      beta: 0.15; B:0.24; 95%CI: 0.14, 0.34). CONCLUSION: In adolescent school
      children, axial elongation-associated increase in DFD was mainly due to an
      enlargement (+300%) of parapapillary gamma zone, while macular BM length
      increased to minor degree (+18%). Gamma zone enlargement was correlated with
      axial elongation-associated vertical optic disc rotation, potentially due to an
      increased backward pull of the optic nerve on the temporal optic disc border.

PMID- 29575806
TI  - Success and failure in replication of genotype-phenotype associations: How does
      replication help in understanding the genetic basis of phenotypic variation in
      outbred populations?
AB  - Recent developments in sequencing technologies have facilitated genomewide
      mapping of phenotypic variation in natural populations. Such mapping efforts face
      a number of challenges potentially leading to low reproducibility. However,
      reproducible research forms the basis of scientific progress. We here discuss the
      options for replication and the reasons for potential nonreproducibility. We then
      review the evidence for reproducible quantitative trait loci (QTL) with a focus
      on natural animal populations. Existing case studies of replication fall into
      three categories: (i) traits that have been mapped to major effect loci
      (including chromosomal inversion and supergenes) by independent research teams;
      (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate
      QTL across multiple populations. Major effect loci, in particular those
      associated with inversions, have been successfully replicated in several cases
      within and across populations. Beyond such major effect variants, replication has
      been more successful within than across populations, suggesting that QTL
      discovered in natural populations may often be population-specific. This suggests
      that biological causes (differences in linkage patterns, allele frequencies or
      context-dependencies of QTL) contribute to nonreproducibility. Evidence from
      other fields, notably animal breeding and QTL mapping in humans, suggests that a
      significant fraction of QTL is indeed reproducible in direction and magnitude at
      least within populations. However, there is also a large number of QTL that
      cannot be easily reproduced. We put forward that more studies should explicitly
      address the causes and context-dependencies of QTL signals, in particular to
      disentangle linkage differences, allele frequency differences and gene-by
      environment interactions as biological causes of nonreproducibility of QTL,
      especially between populations.

PMID- 29575807
TI  - 3-Aminomethyl pyridine chalcone derivatives: Design, synthesis, DNA binding and
      cytotoxic studies.
AB  - Herein we report design, synthesis, and anticancer activity of compounds 6a-h and
      11a-j. Compounds 6a-f were designed based on 3-aminomethyl pyridine attached to
      different acetamide derivatives and in compounds 6g-h it was attached to coumarin
      moiety. Coumarin containing compounds 6g-h showed very poor anticancer activity
      against both A549 (Lungs cancer cell line), and MCF-7 (Breast cancer cell line)
      cell lines in MTT assay. Compounds 11a-j were designed as derivatives of 3
      aminomethyl pyridine and 4-amino chalcones. A series of chalcone derivatives of 3
      aminomethyl pyridine 11a-j have been synthesized and screened for their in vitro
      anticancer activity and DNA binding affinity. Most of the compounds showed very
      good antimitotic activity against A549 cell line as compared to fluorouracil.
      Compounds 11g and 11i were selected for DNA-binding studies as they showed
      excellent activity against cancer cell lines in MTT assay. CT-DNA binding
      affinity of compounds 11g and 11i have been investigated by UV based DNA
      titration and fluorescence emission study against DNA-EtBr complex.
      Interestingly, compound 11i has displayed excellent antiproliferative activity,
      with IC50 0.0067 +/- 0.0002 MUm, against MCF-7 cell line. Compound 11i has been
      studied for its cytotoxicity using MTT, LDH, as well as EtBr/AO assay and was
      found to induce apoptosis in the cancerous cell line.

PMID- 29575808
TI  - Intraoperative difficulties, complications and self-assessed visual function in
      cataract surgery.
AB  - PURPOSE: To study associations between intraoperative difficulties and changes in
      patient-perceived and postoperative visual function and visual satisfaction after
      cataract surgery. METHODS: Swedish multicenter, prospective, cross-sectional,
      nonrandomized, National Cataract Register study. A total of 10 979 patients (n =
      10 979) who underwent cataract surgery from 2008 to 2011 completed the Catquest
      9SF questionnaire before and 3 months postoperatively. Using Rasch analysis, we
      converted the nonparametric grading of the answers to parametric data and
      performed parametric statistical analyses. Multiple regression models were used
      to examine possible predictors associated with self-assessed visual function
      after cataract surgery. RESULTS: Greater improvement in self-assessed visual
      function was seen in patients in whom trypan blue dye was used; those without a
      posterior capsular tear or an ocular comorbidity; and those who were younger,
      female and had low preoperative corrected distance visual acuity (CDVA) or high
      postoperative CDVA compared with their counterparts. Significantly higher self
      assessed postoperative visual function was seen in patients in whom trypan blue
      dye was used and those with no posterior capsular tear or ocular comorbidity and
      no use of capsular hooks; and those who were younger and had low preoperative or
      high postoperative CDVA compared with their counterparts. The risk of general
      dissatisfaction after cataract surgery was significantly greater in patients with
      a posterior capsule tear, ocular comorbidity or low postoperative CDVA, and those
      in whom mechanical pupillary stretching was performed. CONCLUSION: Several
      intraoperative difficulties, posterior capsular tear, ocular comorbidity, age,
      gender, and preoperative and postoperative CDVAs affect patient improvement and
      self-assessed visual function after cataract surgery.

PMID- 29575810
TI  - Use of "Provisional" Designation for Response Criteria.

PMID- 29575809
TI  - IL-37 inhibits invasion and metastasis in non-small cell lung cancer by
      suppressing the IL-6/STAT3 signaling pathway.
AB  - BACKGROUND: IL-37 has been identified as a fundamental inhibitor of inflammatory
      and immunity responses. It plays a crucial protective role in several cancers,
      but its anti-tumor activity and the potential regulatory mechanism of IL-37 in
      non-small cell lung cancer (NSCLC) is largely unclear. METHODS: Enzyme-linked
      immunosorbent assay was used to detect plasma IL-37 expression in NSCLC patients
      and healthy controls. The NSCLC cell line A549 was cultured with recombinant
      human IL-37 or recombinant human IL-6 protein. A549 invasion and metastasis were
      detected using Transwell invasion and scratch wound healing assays, respectively.
      Protein expression of STAT3, pSTAT3, E-cadherin, vimentin, and N-cadherin were
      detected using Western blotting, and messenger RNA expression of STAT3, E
      cadherin, vimentin, and N-cadherin was assessed in each group using real time
      PCR. RESULTS: IL-37 plasma expression was decreased in NSCLC patients, and the
      downregulation of IL-37 was correlated with tumor stage. In vitro, IL-37
      inhibited invasion and migration in A549 cells, while IL-6 promoted invasion and
      migration in A549 cells. pSTAT3, vimentin, and N-cadherin expression was
      increased. E-cadherin expression was lower in the IL-6 group than in the control
      group; however, the opposite pattern was observed in the IL-37 + IL-6 group.
      CONCLUSION: Our results showed that IL-37 plays an inhibitory role in NSCLC
      progression, possibly by suppressing STAT3 activation and decreasing epithelial
      to-mesenchymal transition by inhibiting IL-6 expression. IL-37 could serve as a
      potential novel tumor suppressor in NSCLC.

PMID- 29575811
TI  - Selenadiazole Derivatives Inhibit Angiogenesis-Mediated Human Breast Tumor Growth
      by Suppressing the VEGFR2-Mediated ERK and AKT Signaling Pathways.
AB  - Selenadiazole derivatives (SeDs) have been found to show promise in chemo
      /radiotherapy applications by activating various downstream signaling pathways.
      However, the functional role of SeDs on angiogenesis, which is pivotal for tumor
      progression and metastasis, has not yet been elucidated. In the present study, we
      have examined the antiangiogenic activities of SeDs and elucidated their
      underlying mechanisms. The results showed that the as-synthesized SeDs not only
      enhanced their anticancer activities against several human cancer cells but also
      showed more potent inhibition on human umbilical vein endothelial cells (HUVECs).
      The in vitro results suggested that SeDs, especially 1 a, dose-dependently
      inhibited the vascular endothelial growth factor (VEGF)-induced cell migration,
      invasion, and capillary-like structure formation of HUVECs. Compound 1 a also
      significantly suppressed VEGF-induced angiogenesis in a Matrigel plug assay as
      part of a C57/BL6 mice assay by means of down regulation of VEGF. Furthermore, we
      found that 1 a significantly inhibited MCF-7 human breast tumor growth in nude
      mice without severe systematic cytotoxicity. Compound 1 a was more effective in
      inhibiting cell proliferation and induced a much more pronounced apoptosis effect
      in endothelial cells than MCF-7 cells, which implies that endothelial cells might
      be the primary target of 1 a. Further mechanistic studies on tumor growth
      inhibition effects and neovessel formation suppression demonstrated that 1 a
      inhibited cell viability of MCF-7 and HUVECs by induction of cell apoptosis,
      accompanied by poly(adenosine diphosphate ribose)polymerase (PARP) cleavage and
      caspase activation. Additionally, the 1 a-induced antiangiogenesis effect was
      achieved by abolishing the VEGF-VEGFR2-ERK/AKT (ERK=extracellular signal
      regulated kinases; AKT=protein kinease B) signal axis and enhanced the apoptosis
      effect by triggering reactive oxygen species (ROS)-mediated DNA damage. Taken
      together, these results clearly demonstrate the antiangiogenic potency of SeDs
      and the underlying molecular mechanisms.

PMID- 29575813
TI  - Alloy-Controlled Work Function for Enhanced Charge Extraction in All-Inorganic
      CsPbBr3 Perovskite Solar Cells.
AB  - All-inorganic CsPbX3 (X=I, Br) perovskite solar cells are regarded as cost
      effective and stable alternatives for next-generation photovoltaics. However,
      sluggish charge extraction at CsPbX3 /charge-transporting material interfaces,
      which arises from large interfacial energy differences, have markedly limited the
      further enhancement of solar cell performance. In this work, the work function
      (WF) of the back electrode is tuned by doping alloyed PtNi nanowires in carbon
      ink to promote hole extraction from CsPbBr3 halides, while an intermediate energy
      by setting carbon quantum dots (CQDs) at TiO2 /CsPbBr3 interface bridges electron
      transportation. The preliminary results demonstrate that the matching WFs and
      intermediate energy level markedly reduce charge recombination. A power
      conversion efficiency of 7.17 % is achieved for the WF-tuned all-inorganic
      perovskite solar cell, in comparison with 6.10 % for the pristine device, and
      this is further increased to 7.86 % by simultaneously modifying with CQDs. The
      high efficiency and improved stability make WF-controlled all-inorganic
      perovskite solar cells promising to develop advanced photovoltaic platforms.

PMID- 29575812
TI  - Branched Chain Amino Acids, Androgen Hormones, and Metabolic Risk Across Early
      Adolescence: A Prospective Study in Project Viva.
AB  - OBJECTIVE: This study aimed to examine the associations of two obesity-related
      metabolite patterns with changes in metabolic biomarkers during early
      adolescence. METHODS: Multivariable linear regression was used to examine
      associations of branched chain amino acid (BCAA) and androgen hormone patterns
      with changes in glycemia (fasting glucose, insulin, homeostatic model assessment
      of insulin resistance), adipokines (leptin, adiponectin), inflammation (C
      reactive protein, interleukin-6), lipid profile, and blood pressure during ~5
      years of follow-up among 213 children aged 6 to 10 years at baseline. Covariates
      included baseline age, pubertal status, biomarker level, and BMI percentile, and
      age at follow-up. Interactions with sex and baseline BMI percentile were also
      considered. RESULTS: The median age at baseline was 7.7 years; 48.8% were boys.
      In adjusted models, each 1 unit of the BCAA pattern corresponded with a 4.82 (95%
      CI: 0.92 to 8.71) mg/dL decrease in fasting glucose in boys. In girls, the BCAA
      pattern was associated with an increase in triglycerides (4.17 [0.03 to 8.32]
      mg/dL). The androgen pattern was associated with decreased leptin (-2.35 [-4.34
      to -0.35] ng/dL) and increased C-reactive protein (0.28 [0.03 to 0.54] mg/dL) in
      girls. These relationships did not differ by baseline BMI percentile.
      CONCLUSIONS: The BCAA and androgen hormone metabolite patterns are related to
      changes in metabolic parameters in a sex-specific manner during early
      adolescence.

PMID- 29575814
TI  - Seed phytochemicals shape the community structures of cultivable actinobacteria
      inhabiting plant interiors of Thai pigmented rice.
AB  - We examined abundance, bioactivity, and endophytism of cultivable actinobacteria
      isolated from plant interiors of two Thai pigmented rice cultivars: Hom Nin (HN)
      rice and Luem Pua (LP) glutinous rice. Both rice cultivars housed the same amount
      of endophytic actinobacteria (33 isolates each). Microbispora (76%) and
      Streptomyces (73%) were the predominant endophytic actinobacteria of LP glutinous
      rice and HN rice, respectively. Sphaerisporangium (9%) was found only in LP
      glutinous rice. Twelve percent of endophytic actinobacteria was the possibility
      of discovering novel species from both rice cultivars. Most endophytic
      actinobacteria exhibited plant growth-promoting potentials, including
      antimicrobial activity against test bacteria and phytopathogenic fungi,
      solubilization of phosphate, and production of biostimulants (i.e., ammonia,
      indole-3-acetic acid, and siderophore) and biocatalysts (i.e., amylase,
      cellulase, chitinase, lipase, and protease). Our findings revealed that seed
      phytochemicals of pigmented rice (e.g., anthocyanin, gamma-oryzanol, phytate,
      antioxidants, and content of amylose) were effectors, shaping the community
      structures and biofunctions of endophytic actinobacteria. We conclude that
      pigmented rice is yet a challenging source for discovery of bioactive and novel
      actinobacteria. This study also provides new insights into the plant-endophyte
      interactions by which seed phytochemicals act as a primary checkpoint in the
      natural selection for establishing unique plant endophytomes.

PMID- 29575815
TI  - Impact of age at menarche on obesity and glycemic control in Japanese patients
      with type 2 diabetes: Fukuoka Diabetes Registry.
AB  - AIMS/INTRODUCTION: A younger age at menarche is associated with obesity and type
      2 diabetes in adult life. The impact of early-onset menarche on obesity and
      glycemic control in type 2 diabetes has not been investigated. The present study
      examined the relationship between age at menarche and obesity and glycemic
      control in type 2 diabetes. MATERIALS AND METHODS: A total of 2,133 patients with
      type 2 diabetes aged >=20 years were divided into groups according to age at
      menarche (<=11, 12, 13, 14 and >=15 years). A retrospective cohort study examined
      the association of menarcheal age with adiposity and hemoglobin A1c . RESULTS:
      Age at menarche was inversely associated with body mass index (BMI) and abdominal
      circumference (P < 0.001). Each 1-year decrease in age at menarche was associated
      with a 0.25-kg/m2 and 0.6-cm increase in BMI and abdominal circumference,
      respectively, using a multivariate-adjusted model. Odds ratios for obesity and
      abdominal obesity significantly increased in participants with age at menarche
      <=11 years after multivariable adjustments when age at menarche of 13 years was
      used as the reference (odds ratio 1.95, 95% CI 1.33-2.88, odds ratio 1.95, 95% CI
      1.32-2.87, respectively). Younger age at menarche was significantly associated
      with higher hemoglobin A1c (P < 0.001); however, the association was not
      statistically significant after adjusting for BMI. CONCLUSIONS: Age at menarche
      of <=11 years was associated with obesity after adjusting for confounding
      factors, and poor glycemic control associated with high BMI in type 2 diabetes.
      Age at menarche should be considered during clinical assessments.

PMID- 29575817
TI  - Postfolate spina bifida lesion level change.
AB  - BACKGROUND: Spina bifida accounts for a large proportion of birth defects in the
      United States. Studies have evaluated the decrease in prevalence at birth after
      folate fortification of food grains, but little is known about neurologic
      functional changes related to fortification. This study assesses the functional
      level of lesions in the prefortification and postfortification eras. METHODS:
      Data were collected through retrospective review of medical records from a
      regional multispecialty clinic in Arizona. This study included individuals born
      between 1981-1995 (prefortification) and 1999-2013 (postfortification). Patients
      were included if they had a primary diagnosis of spina bifida with or without
      hydrocephalus. RESULTS: There was a significant difference in functional lesion
      level with an 85% reduction in thoracic level lesions in the postfortification
      era (p < .005). There were no differences in gender or ethnicity across eras;
      however, Hispanic ethnicity had a higher number of cases overall (51.7%). The
      most common lesion level in both eras was mid-lumbar, accounting for 35.7 and
      34.4% of cases in the prefolate and postfolate eras, respectively. CONCLUSIONS:
      This study demonstrates a significant difference in the distribution of lesion
      level of spina bifida patients born in the postfortification era, based on
      neurologic function. Further research with a larger sample size is needed to
      determine if this observation holds true nationally.

PMID- 29575816
TI  - Kidney-Derived c-Kit+ Cells Possess Regenerative Potential.
AB  - Kidney-derived c-Kit+ cells exhibit progenitor/stem cell properties in vitro
      (self-renewal capacity, clonogenicity, and multipotentiality). These cells can
      regenerate epithelial tubular cells following ischemia-reperfusion injury and
      accelerate foot processes effacement reversal in a model of acute proteinuria in
      rats. Several mechanisms are involved in kidney regeneration by kidney-derived c
      Kit+ cells, including cell engraftment and differentiation into renal-like
      structures, such as tubules, vessels, and podocytes. Moreover, paracrine
      mechanisms could also account for kidney regeneration, either by stimulating
      proliferation of surviving cells or modulating autophagy and podocyte
      cytoskeleton rearrangement through mTOR-Raptor and -Rictor signaling, which
      ultimately lead to morphological and functional improvement. To gain insights
      into the functional properties of c-Kit+ cells during kidney development,
      homeostasis, and disease, studies on lineage tracing using transgenic mice will
      unveil their fate. The results obtained from these studies will set the basis for
      establishing further investigation on the therapeutic potential of c-Kit+ cells
      for treatment of kidney disease in preclinical and clinical studies. Stem Cells
      Translational Medicine 2018;7:317-324.

PMID- 29575818
TI  - Collagen-induced arthritis as an animal model of rheumatoid cachexia.
AB  - BACKGROUND: Rheumatoid arthritis is characterized by chronic polyarticular
      synovitis and presents systemic changes that impact quality of life, such as
      impaired muscle function, seen in up to 66% of the patients. This can progress to
      severely debilitating state known as rheumatoid cachexia-without loss of fat mass
      and body weight-for which there is little consensus in terms of diagnosis or
      treatment. This study aims to evaluate whether the collagen-induced arthritis
      (CIA) animal model also develops clinical and functional features characteristic
      of rheumatoid cachexia. METHODS: Male DBA1/J mice were randomly divided into 2
      groups: healthy animals (CO, n = 11) and CIA animals (n = 13). The clinical score
      and edema size, animal weight and food intake, free exploratory locomotion, grip
      strength, and endurance exercise performance were tested 0, 18, 35, 45, 55, and
      65 days after disease induction. After euthanasia, several organs, visceral and
      brown fat, and muscles were dissected and weighed. Muscles were used to assess
      myofiber diameter. Ankle joint was used to assess arthritis severity by
      histological score. Statistical analysis were performed using one-way and two-way
      analyses of variance followed by Tukey's and Bonferroni's test or t-test of
      Pearson and statistical difference were assumed for a P value under 0.05.
      RESULTS: The CIA had significantly higher arthritis scores and larger hind paw
      edema volumes than CO. The CIA had decreased endurance exercise performance total
      time (fatigue; 23, 22, 24, and 21% at 35, 45, 55, and 65 days, respectively),
      grip strength (27, 55, 63, 60, and 66% at 25, 35, 45, 55, and 65 days,
      respectively), free locomotion (43, 57, 59, and 66% at 35, 45, 55, and 65 days,
      respectively), and tibialis anterior and gastrocnemius muscle weight (25 and 24%,
      respectively) compared with CO. Sarcoplasmic ratios were also reduced in CIA (TA:
      23 and GA: 22% less sarcoplasmic ratio), confirming the atrophy of skeletal
      muscle mass in these animals than in CO. Myofiber diameter was also reduced 45%
      in TA and 41% in GA in CIA when compared with the CO. Visceral and brown fat were
      lighter in CIA (54 and 39%, respectively) than CO group. CONCLUSIONS: The CIA
      model is a valid experimental model for rheumatoid cachexia given that the
      clinical changes observed were similar to those described in patients with
      rheumatoid arthritis.

PMID- 29575820
TI  - Laser imaging polarimetry of nacre.
AB  - Nacre is a complex biomaterial made of aragonite-tablet bricks and organic mortar
      that is considerably resilient against breakage. Nacre has been studied with a
      wide range of laboratory techniques, leading to understanding key fundamentals
      and informing the creation of bio-inspired materials. In this article, we present
      an optical polarimetric technique to investigate nacre, taking advantage of the
      translucence and birefringence of its microcomponents. We focus our study on 3
      classes of mollusks that have nacreous shells: bivalve (Pinctada fucata),
      gastropod (Haliotis asinina and Haliotis rufescens) and cephalopod (Nautilus
      pompilius). We sent polarized light from a laser through thin samples of nacre
      and did imaging polarimetry of the transmitted light. We observed clear
      distinctions between the structures of bivalve and gastropod, due to the spatial
      variation of their birefringence. The patterns for cephalopod were more similar
      to bivalve than gastropod. Bleaching of the samples disrupted the transmitted
      light. Subsequent refilling of the bivalve and gastropod nacre samples with oil
      produced optical patterns similar to those of unbleached samples. In cephalopod
      samples, we found that bleaching produced irreversible changes in the optical
      pattern.

PMID- 29575819
TI  - PIK3CA mutations and their response to neoadjuvant treatment in early breast
      cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: PIK3CA mutations frequently occur in breast cancer patients. This
      study was conducted to evaluate the relationship between PIK3CA mutations and
      neoadjuvant treatment response and to analyze the clinical implications. METHODS:
      PubMed, Embase, and the Cochrane database were searched for relevant studies in
      September 2017. The pooled risk ratio (RR) was estimated using fixed effects or
      random effects models according to heterogeneity among studies. RESULTS: This
      meta-analysis included 20 studies with 4392 patients. The pooled RR showed that
      PIK3CA mutation is correlated to lower pathological complete response (pCR) in
      unselected HER2+ patients (RR = 0.73; 95% confidence interval [CI] 0.66-0.81),
      thus the predictive value of PIK3CA status may be stronger in HER2+/HR+ patients
      (RR = 0.50; 95% CI 0.27-0.93) and those administered dual-targeting treatment (RR
      = 0.55; 95% CI 0.39-0.78). In contrast with wild type, either exon 9 (RR = 0.55;
      95% CI 0.39-0.78) or exon 20 (RR = 0.71; 95% CI 0.58-0.89) mutations were
      significantly associated with lower pCR. The predictive value of exon 9 mutations
      was not significantly greater than exon 20 mutations (RR = 0.76; 95% CI 0.51
      1.13). CONCLUSION: In early breast cancer, PIK3CA mutations seem to identify
      HER2+ patients who are less likely to reach pCR. The clinical implications of
      PIK3CA mutations tend to vary between exon 9 and exon 20. This mechanism should
      be explored in further studies.

PMID- 29575821
TI  - Peripheral retinal changes in highly myopic young Asian eyes.
AB  - PURPOSE: To determine the type and prevalence of peripheral retinal changes and
      its relationship with axial length (AL) in a population of young Asian adult
      males. METHODS: This was a cross-sectional study of male subjects aged between 19
      and 25 years old. High myopes [spherical equivalent refraction, (SER) < -6.00 D]
      were recruited and underwent further ocular investigations including dilated
      retinal photography and binocular indirect ophthalmoscopy by two trained
      ophthalmologists. The frequency of peripheral retinal changes within high myopes
      was correlated with axial length and also compared with a group of emmetropes
      (SER between -0.50 D and +1.00 D). RESULTS: A total of 593 high myopes and 156
      emmetropes were recruited. White without pressure (WWOP; n = 458, 46.5%) and
      lattice degeneration (LD; n = 109, 14.6%) were the commonest findings, and their
      prevalence was significantly higher among high myopes (LD, 16.9% versus 5.8%;
      WWOP, 57.2% versus 5.8%; both p < 0.001). Among high myopes, temporal LD was more
      common (71%) and 35% had more than one area in the same eye. Increasing AL was
      associated with LD (odds ratio 1.28, p = 0.01) and retinal holes (odd's ratio
      1.44, p = 0.02) on multivariate analysis. CONCLUSION: White without pressure
      (WWOP) and LD were the commonest peripheral retinal changes. One-third of high
      myopes with LD had more than one area in the same eye. Increasing AL was
      associated with LD and retinal holes. Studies in older adults should be conducted
      to develop clinical guidelines for the management of high myopes.

PMID- 29575822
TI  - Antimicrobial activity of selected essential oils against Streptococcus suis
      isolated from pigs.
AB  - The inhibitory potential by contact and vapor of basil, cinnamon, clove,
      peppermint, oregano, rosemary, common thyme, and red thyme essential oils (EOs)
      against 20 strains of Streptococcus suis was determined by the disk diffusion
      test. The broth microdilution method was used to determine the minimal inhibitory
      and minimal bactericidal concentration (MIC and MBC) of the four selected oils.
      Furthermore, the bactericidal power (ratio MBC/MIC) was calculated. The EOs with
      the major potential in the disk diffusion method were red thyme, common thyme,
      oregano, and cinnamon (? mean 16.5-34.2 mm), whereas cinnamon did not show vapor
      activity. In the microdilution test, all the EOs showed notable antimicrobial
      activity (MIC90 and MBC90 312.5-625 MUg.ml-1 ) and a strong bactericidal power
      (ratio = 1). This is the first study that selects essential oils against S. suis.
      New studies about the possible synergic effect of EOs with antibiotics and about
      toxicity and efficacy in in vivo conditions are recommended.

PMID- 29575823
TI  - Directing-Group-mediated C-H-Alkynylations.
AB  - C-C triple bonds are amongst the most versatile functional groups in synthetic
      chemistry. Complementary to the Sonogashira coupling the direct metal-catalyzed
      alkynylation of C-H bonds has emerged as a highly promising approach in recent
      years. To guarantee a high regioselectivity suitable directing groups (DGs) are
      necessary to guide the transition metal (TM) into the right place. In this Focus
      Review we present the current developments in DG-mediated C(sp2 )-H and C(sp3 )-H
      modifications with terminal alkynes under oxidative conditions and with
      electrophilic alkynylation reagents. We will discuss further modifications of the
      alkyne, in particular subsequent cyclizations to carbo- and heterocycles and
      modifications of the DG in the presence of the alkyne.

PMID- 29575824
TI  - Complex Bayesian Modeling Workflows Encoding and Execution Made Easy With a Novel
      WinBUGS Plugin of the Drug Disease Model Resources Interoperability Framework.
AB  - The Drug Disease Model Resources (DDMoRe) Interoperability Framework (IOF)
      enables pharmacometric model encoding and execution via Model Description
      Language (MDL) and R language, through the ddmore package. Through its components
      and converter plugins, the IOF can execute pharmacometric tasks using different
      target tools, starting from a single MDL-encoded model. In this article, we
      present the WinBUGS plugin and show how its integration in the IOF enables an
      easy implementation of complex Bayesian workflows. We selected a published
      diabetes-linked study as a real-world example, in which two inter-related models
      are used to estimate insulin secretion rate in response to a glucose stimulus
      from intravenous glucose tolerance test (IVGTT) data. This model was implemented
      following different approaches to propagate uncertainty, via diverse IOF target
      tools (NONMEM, WinBUGS, PsN, and Xpose). The developed software supports a
      plethora of pharmacokinetic/pharmacodynamic (PK/PD) modeling features. It
      provides solutions to reproducibility and interoperability issues in Bayesian
      modeling, and facilitates the difficult encoding of complex PK/PD models in
      WinBUGS.

PMID- 29575825
TI  - Effect of lactulose intervention on gut microbiota and short chain fatty acid
      composition of C57BL/6J mice.
AB  - Gut microbiota have strong connections with health. Lactulose has been shown to
      regulate gut microbiota and benefit host health. In this study, the effect of
      short-term (3 week) intervention of lactulose on gut microbiota was investigated.
      Gut microbiota were detected from mouse feces by 16S rRNA high-throughput
      sequencing, and short chain fatty acids (SCFAs) were detected by gas
      chromatography-mass spectrometry (GC-MS). Lactulose intervention enhanced the
      alpha-diversity of the gut microbiota; increased the abundance of hydrogen
      producing bacteria Prevotellaceae and Rikenellaceae, probiotics
      Bifidobacteriaceae and Lactobacillaceae, and mucin-degrading bacteria Akkermansia
      and Helicobacter; decreased the abundance of harmful bacteria Desulfovibrionaceae
      and branched-chain SCFAs (BCFAs). These results suggest that lactulose
      intervention effectively increased the diversity and improved the structure of
      the intestinal microbiota, which may be beneficial for host health.

PMID- 29575827
TI  - Upcoming events of interest.

PMID- 29575826
TI  - Paraganglioma: Cytomorphologic features, radiologic and clinical findings in 12
      cases.
AB  - BACKGROUND: The cytologic diagnosis of paraganglioma can be challenging because
      of its rarity, wide anatomic distribution, and variable cytomorphological
      features. DESIGN: The Johns Hopkins Hospital pathology archives were searched for
      fine-needle aspiration (FNA) specimens confirmed as paraganglioma on histology
      (2003-2015). RESULTS: Twelve specimens from 10 patients (6 males and 4 females)
      with an age range of 16-81 years (mean = 47) were included. Anatomic location
      included neck (n = 4), paraspinal (n = 2), retroperitoneum (n = 2), and
      peripancreatic (n = 2). Cellularity of cytological specimens ranged from scant to
      hypercellular. The cells were arranged in clusters (n = 7), single cells (n = 6),
      acini (n = 3), and syncytium (n = 1). Plasmacytoid (n = 5) and spindled cells (n
      = 6) were often present. Nuclear details included anisonucleosis (n = 8), marked
      pleomorphism (n = 8), scattered binucleation and/or multinucleation, nuclear
      knobbing (n = 2), speckled (n = 3), coarse (n = 2), hyperchromatic chromatin (n =
      3), nuclear grooves (n = 6), intranuclear pseudoinclusions (n = 2), prominent
      nucleoli (n = 1), naked nuclei (n = 7), and rare nuclear streaking artifact (n =
      2). Cytoplasm was delicate, abundant, and granular (n = 9). Necrosis (n = 1) was
      rare. Synaptophysin, chromogranin, CD56, and S100 (only in sustentacular cells)
      were positive in tested cases. Three cases showed loss of Succinate Dehydrogenase
      Subunit B (SDHB). Two patients developed metachronous lesions at different sites.
      Three patients developed recurrence at the surgical site. Metastatic
      paraganglioma to the lymph nodes (n = 2), bone (n = 1), and lung (n = 1) also
      occurred. CONCLUSION: An accurate diagnosis of paraganglioma on FNA specimens is
      crucial for proper treatment. SDH status should be considered for all patients
      with paraganglioma as it may be important for patients' lifelong follow-up as
      well as for familial considerations. Paraganglioma is a rare entity with wide age
      and anatomic distribution and variable cytomorphological features that often
      overlap with those of malignant neoplasms. Possible aggressive behavior such as
      recurrence and metastasis to lymph nodes, bone, and lung as well as Succinate
      Dehydrogenase complex mutations warrant an accurate diagnosis on aspirated
      material for appropriate clinical management.

PMID- 29575828
TI  - The Heart in Rheumatic, Autoimmune and Inflammatory Diseases: Pathophysiology,
      Clinical Aspects and Therapeutic Approaches, 1st edition.

PMID- 29575829
TI  - Optical coherence tomography retinal image reconstruction via nonlocal weighted
      sparse representation.
AB  - We present a nonlocal weighted sparse representation (NWSR) method for
      reconstruction of retinal optical coherence tomography (OCT) images. To
      reconstruct a high signal-to-noise ratio and high-resolution OCT images,
      utilization of efficient denoising and interpolation algorithms are necessary,
      especially when the original data were subsampled during acquisition. However,
      the OCT images suffer from the presence of a high level of noise, which makes the
      estimation of sparse representations a difficult task. Thus, the proposed NWSR
      method merges sparse representations of multiple similar noisy and denoised
      patches to better estimate a sparse representation for each patch. First, the
      sparse representation of each patch is independently computed over an
      overcomplete dictionary, and then a nonlocal weighted sparse coefficient is
      computed by averaging representations of similar patches. Since the sparsity can
      reveal relevant information from noisy patches, combining noisy and denoised
      patches' representations is beneficial to obtain a more robust estimate of the
      unknown sparse representation. The denoised patches are obtained by applying an
      off-the-shelf image denoising method and our method provides an efficient way to
      exploit information from noisy and denoised patches' representations. The
      experimental results on denoising and interpolation of spectral domain OCT images
      demonstrated the effectiveness of the proposed NWSR method over existing state-of
      the-art methods.

PMID- 29575831
TI  - In vivo high-resolution cortical imaging with extended-focus optical coherence
      microscopy in the visible-NIR wavelength range.
AB  - Visible light optical coherence tomography has shown great interest in recent
      years for spectroscopic and high-resolution retinal and cerebral imaging. Here,
      we present an extended-focus optical coherence microscopy system operating from
      the visible to the near-infrared wavelength range for high axial and lateral
      resolution imaging of cortical structures in vivo. The system exploits an
      ultrabroad illumination spectrum centered in the visible wavelength range
      (lambdac  =  650  nm, Deltalambda  ~  250  nm) offering a submicron axial
      resolution (~0.85  MUm in water) and an extended-focus configuration providing a
      high lateral resolution of ~1.4  MUm maintained over ~150  MUm in depth in water.
      The system's axial and lateral resolution are first characterized using phantoms,
      and its imaging performance is then demonstrated by imaging the vasculature,
      myelinated axons, and neuronal cells in the first layers of the somatosensory
      cortex of mice in vivo.

PMID- 29575830
TI  - Quantitative real-time optical imaging of the tissue metabolic rate of oxygen
      consumption.
AB  - The tissue metabolic rate of oxygen consumption (tMRO2) is a clinically relevant
      marker for a number of pathologies including cancer and arterial occlusive
      disease. We present and validate a noncontact method for quantitatively mapping
      tMRO2 over a wide, scalable field of view at 16  frames  /  s. We achieve this by
      developing a dual-wavelength, near-infrared coherent spatial frequency-domain
      imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption,
      MUa, and reduced scattering, MUs', parameters) as well as the speckle flow index
      (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration ( 
      [  HbO2  ]   and [HHb]) are calculated from optical properties and combined with
      SFI to calculate tMRO2. We validate the system using a series of yeast-hemoglobin
      tissue-simulating phantoms and conduct in vivo tests in humans using arterial
      occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its
      repayment. Finally, we image the impact of cyanide exposure and toxicity reversal
      in an in vivo rabbit model showing clear instances of mitochondrial uncoupling
      and significantly diminished tMRO2. We conclude that dual-wavelength cSFDI
      provides rapid, quantitative, wide-field mapping of tMRO2 that can reveal unique
      spatial and temporal dynamics relevant to tissue pathology and viability.

PMID- 29575832
TI  - [Circulating tumor DNA and targeted therapy in colorectal cancer].
AB  - The detection of circulating tumor DNA is a quick, low cost and reliable approach
      of liquid biopsy of cancer. It has a wide range of applications for tumor
      screening because of its noninvasive, convenient and highly repeatable features.
      In terms of the targeted therapy in patients with colorectal cancer, serial
      monitoring of circulating tumor DNA, especially for the specific genetic
      alterations, can be used for prognosis, monitoring resistance, evaluation of
      therapeutic effects and screening combined targeted therapy. Therefore, it will
      guide more precise treatment of colorectal cancer.

PMID- 29575833
TI  - [Incidence and mortality of female breast cancer in China, 2014].
AB  - Objective: To estimate the incidence and mortality of female breast cancer in
      China based on the cancer registration data in 2014, collected by the National
      Central Cancer Registry (NCCR), and to provide support data for breast cancer
      prevention and control in China. Methods: There were 449 cancer registries
      submitting female breast cancer incidence and deaths data occurred in 2014 to
      NCCR. After evaluating the data quality, 339 registries' data were accepted for
      analysis and stratified by areas (urban/rural) and age group. Combined with data
      on national population in 2014, the nationwide incidence and mortality of female
      breast cancer were estimated. Chinese population census in 2000 and Segi's
      population were used for age-standardized incidence/mortality rates. Results:
      Qualified 339 cancer registries covered a total of 288 243 347 populations (144
      061 915 in urban and 144 181 432 in rural areas) in 2014. The morphology verified
      cases (MV%) accounted for 87.42% and 0.59% of incident cases were identified
      through death certifications only (DCO%), with mortality to incidence ratio of
      0.24. The estimates of new breast cancer cases were about 278 900 in China in
      2014, accounting for 16.51% of all new cases in female. The crude incidence rate,
      age-standardized rate of incidence by Chinese standard population (ASRIC), and
      age-standardized rate of incidence by world standard population (ASRIW) of breast
      cancer were 41.82/100 000, 30.69/100 000, and 28.77/100 000, respectively, with a
      cumulative incidence rate (0-74 age years old) of 3.12%. The crude incidence
      rates and ASRIC in urban areas were 49.94 per 100 000 and 34.85 per 100 000,
      respectively, whereas those were 31.72 per 100 000 and 24.89 per 100 000 in rural
      areas. The estimates of breast cancer deaths were about 66 000 in China in 2014,
      accounting for 7.82% of all the cancer-related deaths in female. The crude
      mortality rate, age-standardized rate of mortality by Chinese standard
      population(ASRMC) and age-standardized rate of mortality by world standard
      population (ASRMW) of breast cancer were 9.90/100 000, 6.53/100 000, and 6.35/100
      000, respectively, with a cumulative mortality rate of 0.69%. The crude mortality
      rates and ASRMC in urban areas were 11.48 per 100 000 and 7.04 per 100 000,
      respectively, whereas those were 7.93 per 100 000 and 5.79 per 100 000 in rural
      areas. The incidence and mortality rates of breast cancer were higher in areas
      than those in rural areas. The age-specific incidence rates of breast cancer
      increased greatly after 20 years old and peaked at the age group of 55-60. The
      age-specific mortality rates increased rapidly with age, particularly after 25
      years old. They remained at a relative stable level from 55 to 65 years of age,
      and then increased dramatically and peaked in the age group of 85 and above.
      Conclusions: Breast cancer is still one of the most common malignant tumor
      threatening to famale health in China. The disease is more prevalent in urban
      areas at the age group of 55-60. Comprehensive prevention and control strategies
      referring to local status and age groups should be carried out to reduce the
      burden of breast cancer.

PMID- 29575834
TI  - [Effect and mechanism of antimicrobial peptide cathelicidin secreted by tumor
      associated macrophage on the growth of colorectal cancer in mice].
AB  - Objective: To investigate the effect and mechanism of the antibacterial peptide
      cathelicidin secreted by tumor associated macrophages on the growth of colorectal
      cancer in mice. Methods: Azoxymethane (AOM)/ dextran sodium sulfate (DSS) method
      was used to establish a mouse model of colitis associated colon cancer. To induce
      tumor formation, cathelicidin antibody, IgG antibody (positive control) or PBS
      (negative control) was respectively injected into mice once every 3 days and
      lasted one month. Then the pictures of mice colon were taken, and the numbers of
      tumor were counted and evaluated. Expressions of cathelicidin in tumor associated
      macrophages isolated from tumor and adjacent normal tissues of mice were examined
      by quantitative RT-PCR (qRT-PCR) and Western blot. Expressions of the tumor
      proliferating antigen Ki-67, macrophage marker CD68 and cathelicidin in tumor and
      non-tumor tissues were determined by immunohistochemistry analysis. Apoptosis of
      cells from tumor tissues was analyzed by using TdT-mediated dUTP nick-end
      labeling (TUNEL). Results: In colon tumor tissues, cathlicidin strongly expressed
      in inflammatory cells (macrophages), but weakly expressed in tumor cells. The
      tumor number and size in mice injected with cathelicidin neutralizing antibody
      were 4.50+/-1.18 and (1.74+/-0.18) mm, respectively, significantly lower than
      13.88+/-1.98 and (3.74+/-0.38) mm of mice injected with PBS (t=4.07, t=4.72; P<
      0.01) and 15.25+/-1.82 and (3.40+/-0.36) mm of mice injected with IgG antibody
      (t=4.96, t=4.08; P<0.01). The Ki-67 positive rate of cells in tumor tissues of
      mice injected with cathelicidin neutralizing antibody was (28.20+/-3.44) %,
      significantly lower than (68.20+/-3.51) % of mice injected with PBS (t=8.135,
      P<0.01) and (69.20+/-3.41) % of mice injected with IgG antibody (t=8.461,
      P<0.01). Immunohistochemistry analyses showed that the expression of CD68 in
      tumor tissues of mice injected with cathelicidin antibody was significantly lower
      than that of mice injected with IgG antibody or PBS. TUNEL result showed that
      treatment with cathelicidin neutralizing antibody had negligible effect on the
      apoptosis of tumor cells. Conclusions: Cathelicidin secreted by tumor associated
      macrophages can promote the growth of colorectal cancer in mice, and neutralizing
      cathelicidin activity can inhibit the growth and proliferation of colorectal
      cancer. Cathelicidin mediated promotion of colon cancer proliferation may mainly
      be exerted by recruiting inflammatory cells such as macrophages into the tumor
      microenvironment.

PMID- 29575835
TI  - [The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse
      breast cancer model].
AB  - Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which
      carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1
      hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer
      effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in
      mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the
      cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic
      HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different
      concentrations (0, 2, 4 and 8 MUg/ml). The effects of oncolytic HSV1-hGM-CSF and
      doxorubicin on the tumor growth, survival time and their side effects on the
      mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and
      doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro.
      Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity
      of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment
      with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice
      were (144.40+/-27.68)mm(3,) (216.80+/-57.18)mm(3,) (246.10+/-21.90)mm(3,)
      (327.50+/-44.24)mm(3,) (213.30+/-32.31)mm(3) and (495.80+/-75.87)mm(3) in the
      groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined
      with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low
      dose HSV1-hGM-CSF alone and control, respectively.Compared with the control
      group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant
      reduction of primary tumor volume in vivo (P<0.001). The median survival times
      were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above,
      respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM
      CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of
      control (P<0.05). Conclusion: Synergistic effect of sequential treatment with
      doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.

PMID- 29575836
TI  - [Expression level and clinical significance of LncRNA HOXA11-AS in esophageal
      squamous cell carcinoma patients].
AB  - Objective: To explore the expression of long noncoding RNA (lncRNA) HOXA11-AS in
      esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS
      level with clinical outcomes. Methods: Quantitative real-time polymerase chain
      reaction (qRT-PCR) was applied to detect the expression level of HOXA11-AS in
      cell lines HET-1A, EC9706, EC109, and in tumor tissue and paired adjacent tissue
      samples from 73 ESCC patients who received surgical resection.The correlations of
      the expression level of HOXA11-AS with clinicopathological features and prognosis
      were also analyzed. Results: The relative expression levels of HOXA11-AS in tumor
      tissue and paired adjacent tissue were 0.832+/-0.387 and 2.486+/-1.087,
      respectively, with significant difference (P<0.001). The expression of HOXA11-AS
      was upregulated in 63.0%(46/73)ESCC tissues. The relative expression levels of
      HOXA11-AS in HET-1A, EC-9706 and EC-109 cells were 1.000, 23.553+/-3.221 and
      17.217+/-1.968, respectively. The expression level of HOXA11-AS was upregulated
      in ESCC cell lines (P<0.001). High expression level of HOXA11-AS was correlated
      with histological grade and lymph node metastasis of ESCC patients (P<0.05).
      However, it was not associated with the age, gender, depth of infiltration and
      TNM staging (P>0.05). The median overall survival (OS) and median disease-free
      survival (DFS) of patients with low HOXA11-AS expression were 43 months and 42
      months, respectively, significantly longer than 37 months and 28 months of
      patients with HOXA11-AS high expression (P<0.05). Cox model multivariate analysis
      showed that the expression of HOXA11-AS and lymph node metastasis were
      independent factors of poor prognosis of ESCC patients. Conclusions: The
      expression of HOXA11-AS is upregulated in esophageal cancer cell lines and
      tissues. High expression of HOXA11-AS is associated with poor prognosis of ESCC
      patients.Therefore, LncRNA HOXA11-AS may serve as a predictive marker of
      postoperative ESCC patients.

PMID- 29575837
TI  - [Clinical value of endoscopicultrsaonography and multi-slice spiral CT in Siewert
      IIand III type adenocarcinoma of esophagogastric junction].
AB  - Objective: To investigate the clinical value of endoscopic ultrasonography (EUS)
      and Multi-slice Spiral CT (MSCT) in the preoperativestaging of tumor(T) and lymph
      node (N) metastasis in patients with SiewertIIand III typeadenocarcinoma of
      esophagogastric junction(AEG). Methods: Clinical data of 145 Siewert II and III
      type AEG patientswithout preoperative chemoradiotherapy were retrospectively
      reviewed. Theyall received preoperative EUS and MSCT examination and underwent
      surgical resection, and the results of EUS and MSCT were compared with their
      postoperative pathologic staging. Results: The sensitivity, specificity, and
      accuracy of EUS for T stage in Siewert II and III type AEG were higher than those
      of MSCT. The total accuracy of EUS and MSCT were 90.3% and 63.5%, respectively,
      and the difference was statistically significant (chi(2)=29.52, P<0.01). The
      sensitivity of EUS for T1, T2 and T3 were 89.5%, 91.1% and 85.2%, respectively,
      which were significantly higher than 42.1%, 66.7% and 29.6% of MSCT (chi(2)=9.47,
      P<0.01 for T1; chi(2)=8.07, P<0.01 for T2; chi(2)=17.40, P<0.01 for T3). In
      addition, the total accuracy of EUS and MSCT for lymph node metastasis status of
      Siewert II and III type AEG were 75.9% and 64.8%, respectively, showing a
      statistically significant difference(chi(2)=4.23, P=0.04). The sensitivity of EUS
      for N1 and N2 were 82.1% and 79.2%, respectively, which were significantly higher
      than 53.6% and 60.4% of MSCT (chi(2)=5.24, P=0.02; chi(2)=4.48, P=0.03). There
      was no statistical significance for sensitivity of EUS and MSCT in N0 and N3
      (P>0.05). Conclusion: EUS diagnosis of T and N staging in Siewert II/III type AEG
      showed significantly greater performance than MSCT.

PMID- 29575838
TI  - [Study on the relationship between ultrasonographic features of papillary thyroid
      carcinoma and central cervical lymph node metastasis].
AB  - Objective: To investigate the correlation between ultrasonographic features of
      papillary thyroid carcinoma and central cervical lymph node metastasis. Methods:
      We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC),
      pathologically confirmed after surgery in Tianjin Medical University Cancer
      Institute & Hospital. All patients were divided into central cervical lymph node
      metastasis group and non-metastasis group. No lateral cervical lymph node
      metastasis was found in preoperative ultrasonography and postoperative pathology.
      The characteristics of the ultrasound was observed and analyzed. Results: 297 out
      of 486 patients with papillary thyroid carcinomahad central metastasis, and the
      other 189 cases did not. Take pathology results as a standard, the sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy
      rate of preoperative ultrasound diagnosis in PTC patients with central cervical
      lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively.
      Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm,
      located in the lower pole, ill-defined margin, hypoechogenicity, micro
      calcification, capsule invasion more than 1/4 perimeter of papillary thyroid
      carcinoma were significantly associated with central cervical lymph node
      metastasis (all P<0.05). Multivariate analysis showed that diameter>1 cm, micro
      calcification, capsule invasion more than 1/4 perimeter of papillary thyroid
      carcinoma became independent risk factors of central cervical neck lymph node
      metastasis (all P<0.05). Conclusions: Preoperative description of
      ultrasonographical features has important value to assess central cervical lymph
      node metastasis in patients with papillary thyroid carcinoma. More information
      could be provided for clinical treatment. When the papillary thyroid carcinoma
      presented as diameter>1 cm, micro-calcification, and capsule invasion more than
      1/4 perimeter of, there will be a greater risk of central cervical lymph node
      metastasis, and we shall suggest prophylactic central lymph cervical node
      dissection.

PMID- 29575839
TI  - [Clinicopathological features of second primary lung cancer and pulmonary
      metastasisin patients with breast cancer].
AB  - Objective: To compare the clinicopathological characteristics of second primary
      lung cancer following breast cancer and lung metastases from breast cancer, and
      then to analyze the risk factors in breast cancer patients with second primary
      lung tumor. Methods: Clinical data of 55 breast cancer patients with second
      primary lung tumor and 205 breast cancer patients with solitary pulmonary
      metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were
      retrospectively analyzed. The risk factors of primary lung cancer following
      breast cancer were analyzed using logistic regression model. Results: Second
      primary lung cancer in patients with first breast cancer accounted for
      approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and
      0.84%(55/6 580) of all breast cancer patients. The median intervals between the
      diagnosis of second primary lung cancer or lung metastasis and first breast
      cancer were 52 months and 42 months, respectively. These two groups showed
      significant difference between age, time interval between diagnoses, breast tumor
      size, axillary lymph node metastasis, estrogen receptor, molecular subtype
      (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A
      multivariate logistic regression model confirmed that age (OR=1.088, P<0.001),
      breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460,
      P=0.004) were all independent factors for second primary lung cancer.
      Conclusions: For isolated pulmonary nodules in patients with breast cancer,
      especially for those with elder age, larger tumor size and radiotherapy history,
      we should distinguish the second primary lung cancer from pulmonary metastasis.
      The treatment regimen for lung metastasis and primary lung cancer in patients
      with breast cancer are entirely distinct. The timely histopathology examinations
      for pulmonary nodes in patients with breast cancer are recommended.

PMID- 29575840
TI  - [Analysis of 17 cases underwent laparoscopic rectal cancer surgery with transanal
      natural orifice specimen extraction and resection].
AB  - Objective: To study the feasibility, safety and short-term efficacy of total
      laparoscopic rectal cancer surgery with transanal natural orifice specimen
      extraction and resection. Methods: From May 2014 to March 2016, 17 patients with
      rectal carcinoma were treated by total laparoscopic rectal cancer surgery with
      transanal natural orifice specimen extraction and resection. The clinical data of
      these patients was collected and retrospectively analyzed to assess the impact of
      the operation on postoperative recovery time and the incidence of complications.
      Results: All operations had been successfully accomplished without conversion to
      open surgery or conversional laparoscopic-assisted surgery . The median operative
      time was 105 minutes. The median blood loss was 35 ml. The median proximal and
      distal margin of tumor is 16 cm and 3.5 cm. The median number of lymph nodes
      harvest is 21, and the median first bowl movement is 43 hours. The
      hospitalization after operation is 8 days. No patient underwent abdomen
      hemorrhage or anastomotic leakage. Conclusion: Laparoscopic rectal cancer surgery
      with transanal natural orifice specimen extraction and resection appears to be
      feasible, safe and with promising efficacy for selected patients.

PMID- 29575841
TI  - [Clinical application of LDLT after reconstruction of IVC using artificial blood
      vessel in the treatment of HCC beyond Milan Criteria].
AB  - Objective: To assess application of reconstruction of retrohepatic inferior vena
      cava using artificial blood vessel in right lobe living donor liver
      transplantation (LDLT) in the treatment of hepatocellular carcinoma (HCC) beyond
      Milan Criteria. Methods: The clinical data of 9 HCC patients who underwent right
      lobe liver transplantation after reconstruction of retrohepatic inferior vena
      cava using artificial blood vessel between June 2015 and Nov 2016 at Liver
      Transplantation Center of the First Affiliated Hospital of Nanjing Medical
      University were retrospectively analyzed. The liver of the patients was removed
      with retrohepatic inferior vena cava, and then the right donor graft was
      implanted by conventional orthotopic liver transplantation. Results: All 9 liver
      transplantations were performed successfully. The time of reconstruction of
      hepatic venous outflow of the donor graft was (22.6+/-3.0) min, anhepatic time
      was (45.0+/-7.1) min, and total operation time was (321.9+/-52.5) min. All
      patients recovered uneventfully, ICU and hospital stay day were (1.2+/-0.4) days
      and (18.4+/-3.0) days. 2 patients suffered from thrombosis of artificial blood
      vessel, one recovered after conservative treatment and another was treated by
      placement of vein stent. No abdominal/pulmonary infection and non-artificial
      blood vascular complications were found, and none died in perioperative period.
      Postoperative pathological results showed that all patients were hepatocellular
      carcinomas and vascular tumor thrombosis was found in 5 cases. All patients were
      follow up, 1 patient died of pulmonary and brain metastasis 10 months after
      operation. One patient survived with local recurrence of tumor in liver. The
      other patients had no tumor recurrence and metastasis. Conclusion: Replacement of
      retrohepatic inferior vena cava using artificial blood vessel in right lobe
      living donor liver transplantation is safe and feasible in the treatment of HCC
      beyond Milan Criteria, and might improve the resection rate of diseased liver and
      the prognosis of HCC patients after living donor liver transplantation.

PMID- 29575842
TI  - [Prostate metastasis of lung cancer: a case report].

PMID- 29575843
TI  - [Application value of real-time three-dimensional contrast-enhanced ultrasound
      for morphological assessing of hepatocellular carcinoma before radiofrequency
      ablation treatment].
AB  - Objective: To investigate the evaluating ability of real-time three-dimensional
      contrast-enhanced ultrasound (RT-3D-CEUS) for morphology of hepatocellular
      carcinoma (HCC) before radiofrequency ablation (RFA) treatment. Methods: Sixty
      patients with 88 targeted lesions were enroll in this study, who have received
      RFA in Hangzhou Xiasha Hospital. The pretreatment imaging data of CEUS and RT-3D
      CEUS were retrospective analysis. Morphological features were assessed according
      to the size and shape of the lesions, and were compared between two modalities
      with the post-treatment response as the reference standard. Results: The size of
      lesion measured by CEUS and RT-3D-CEUS was similar in 70 out of 88 lesions (group
      A). In the other 18 lesions, the size measured by RT-3D-CEUS was larger than that
      by CEUS (group B). For the shape analysis, 38 lesions were spheroid by CEUS and
      34 lesions by RT-3D-CEUS; 47 lesions were oval by CEUS and 41 lesions by RT-3D
      CEUS; 3 lesions were irregular by CEUS and 13 lesions by RT-3D-CEUS. There were
      78 lesions which shape assessed by two modalities consistently (group A'), and
      the other 10 lesions with inconsistent shape by two modalities (group B'). Three
      months follow-up results showed that 4 lesions appeared tumor residue (5.7%) in
      group A' and 6 lesions (33.3%) in group B'. There was significant difference
      between these two groups (P=0.004). In the group A', there were 6 lesions (7.7%)
      showed tumor residue, and 4 lesions (40.0%) in group B'. The difference between
      these two groups was also significant (P=0.012). Conclusion: RT-3D-CEUS could be
      used to assess the size and shape of HCC accurately which is associated with the
      response of RFA.

PMID- 29575844
TI  - [Multi-variated analysis of differential diagnosis in ultrasonography of
      idiopathic granulomatous mastitis and invasive ductal carcinoma].
AB  - Objective: To evaluate the differential diagnosis of idiopathic granulomatous
      mastitis (IGM) and invasive ductal carcinoma. Methods: The ultrasonographic data
      of 37 IGM patients and 50 cases of IDC were analyzed retrospectively. The shape,
      growth direction, margin, internal echo, posterior echo, calcification, Adler
      blood flow classification, PSV(peak sestolic velocity), RI (resistance index)and
      elasticity scores were analyzed by chi(2) test and independent sample t test. The
      optimal cutoff values of age, PSV and RI were calculated by receiver operating
      characteristic (ROC) curve. Logistic regression analysis was used to calculate
      the odds ratio (OR) of ultrasonic variates in the diagnosis of both diseases.
      Results: There were no significant differences in the shape, margin, internal
      echo and blood flow grading between the two groups. The age, lesion growth
      direction, posterior echo, calcification, PSV, RI and elasticity were
      statistically different. The cut-of value of Age, PSV and RI were 38.5 years old,
      13.20 cm/s, and 0.655. Logistic regression multi-variated analysis revealed that
      elastic score (OR=9.806) had the best value of the differential diagnosis, as
      well as calcification (OR=6.937), posterior echo decay (OR=4.613), RI (OR=3.257),
      lesion growth orientation (OR=3.198), and PSV (OR=1.202). Lesion shape, margin,
      internal echo, and Adler blood flow classification did not help in differential
      diagnosis. Conclusion: Ultrasound multi-parameter analysis has high value in IGM
      and IDC differential diagnosis.

PMID- 29575845
TI  - [Analysis of the factors associated with the long-term curative effect and
      prognosis of primary vaginal carcinoma].
AB  - Objective: To investigate the clinical factors that affect the prognosis of
      patients with primary vaginal cancer. Methods: Clinical data of 118 primary
      vaginal cancer patients with pathological diagnosis and clinical follow-up data
      from the Department of Gynecology of Liaoning Cancer Hospital & Institute from
      1999 to 2014 were collected and retrospectively analyzed. The relationship of
      prognosis and factors including age, history of hysterectomy, pathological types,
      International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size,
      tumor location and therapeutic methods were analyzed, respectively. Results: The
      median survival time of the 118 patients was 93 months. The survival rates of 1,
      3, 5, 10 and 15-year were 89.7%, 68.1%, 60.4%, 37.3% and 19.0%, respectively.The
      results of univariate analysis showed that the FIGO stage, pathological types,
      tumor size, therapeutic methods and tumor location were related to the prognosis
      of patients with primary vaginal cancer (all P<0.05), while the patients' age,
      history of hysterectomy were not (all P>0.05). The results of Cox multivariate
      regression analysis indicated that FIGO stage (P=0.008), tumor location (P=0.001)
      and therapeutic methods (P=0.007) were independent prognostic factors of the
      patients with primary vaginal cancer. Conclusions: Prognostic factorsofpatients
      with primary vaginal cancer include FIGO stage, pathological types, tumor size,
      therapeutic methods and tumor location. Among them, therapeutic methods and tumor
      location are the independent prognostic factors.

PMID- 29575846
TI  - [Evaluation of CIN2+ /CIN3+ risk of different HPV subtypes infection combined
      with abnormal cytology status].
AB  - Objective: To determine the morbidity of cervical intraepithelial neoplasia 2+
      (CIN2+ ) and CIN3+ of different human papillomavirus(HPV) subtype infection
      combined with different cytology status. Methods: The Shenzhen Cervical Cancer
      Screening Trial I & II (SHENCCASTI&II) are population-based cross-sectional
      cervical cancer screening studis conducted in Shenzhen and surrounding area from
      2008 to 2010. A total of 12 097 women who aged 25-59 years were included in the
      analysis. All of these women were detected by liquid-based cytology test and
      several high-risk HPV-DNA tests. The ones with HPV positive or atypical squamous
      cells of undetermined sign (ASC-US) were sequentially conducted by cervical
      biopsy vaginoscopy. Finally, 10 805 samples with complete data of hybrid capture
      2(HC2), the polymerase chain reaction-based matrix-assisted laser
      desorption/ionization time-of-flight assay (MALDI-TOF), HPV genotyping detection,
      cytology and pathology results were analyzed. Results: The top 6 infection rates
      of HR-HPV in CIN2+ and CIN3+ were HPV16, HPV52, HPV58, HPV33, HPV31, HPV18. The
      highest constituent ratio of cytology in CIN2+ and CIN3+ was high grade squamous
      intraepithelial lesion(HSIL). The morbidities of CIN2+ of patients infected with
      HPV16, HPV31, HPV58, HPV33, HPV18, HPV52 were 41.3%, 31.5%, 30.6%, 28.7%, 28.2%,
      17.7%, respectively, while the morbidities of CIN3+ of those were 33.5%, 20.5%,
      19.4%, 15.7%, 19.2%, 8.3%, respectively.The morbidities of CIN2+ in negative
      intraepithelial lesion or malignancy (NILM), ASC-US, low grade squamous
      intraepithelial lesion (LSIL), atypical squamous cell cannot exclude high-grade
      squamous intraepithelial lesion (ASC-H), high grade squamous intraepithelial
      lesion (HSIL), atypical glandular cell (AGC) samples were 0.4%, 6.9%, 11.1%,
      36.4%, 82.0%, 16.7%, respectively, while the morbidities of CIN3+ of those were
      0.2%, 3.1%, 4.2%, 22.7%, 64.8%, 0.0%, respectively. The morbidities of CIN2+ in
      NILM combined with HPV16, HPV18, HPV31, HPV33 infection were 12.6%, 13.3%, 15.8%
      and 11.5%, respectively, while the morbidities of CIN3+ of those were 10.3%,
      11.1%, 7.9% and 7.7%, respectively.The morbidities of CIN2+ and CIN3+ in ASC-US
      combining with hrHPV infection were high, and the top 6 subtypes associated with
      high risk of CIN2+ were HPV31 (35.7%), HPV33 (26.9%), HPV16 (26.5%), HPV58
      (22.4%), HPV52 (18.6%), HPV68 (15.4%), while those associated with high risk of
      CIN3+ were HPV16 (20.4%), HPV31 (14.3%), HPV33 (11.5%), HPV58 (8.6%), HPV68
      (7.7%), HPV52 (5.8%). Conclusions: Cytology combined with HPV genotyping
      detection can more effectively estimate the morbidity risks of CIN2+ and CIN3+ .
      Both high prevalence rates and high risks associated with CIN2+ and CIN3+ of
      HPV31, HPV33, HPV52 and HPV58 are observed. NILM and ASC-US status combined with
      these subtypes mentioned above are advised to be conducted by colposcopy.

PMID- 29575847
TI  - [Calcified intraparenchymal schwannoma of the temporal lobe: a case report].

PMID- 29575848
TI  - Does learning style preferences influence academic performance among dental
      students in Isfahan, Iran?
AB  - PURPOSE: The present study aimed to identify the learning preferences of dental
      students and to characterize their relationship with academic performance at a
      dental school in Isfahan, Iran. METHODS: This cross-sectional descriptive study
      included 200 undergraduate dental students from October to November 2016. Data
      were collected using a 2-part questionnaire. The first part included demographic
      data, and the second part was a Persian-language version of the visual, aural,
      read/write, and kinesthetic questionnaire. Data analysis was conducted with the
      chi-square test, 1-way analysis of variance, and multiple linear regression.
      RESULTS: The response rate was 86.6%. Approximately half of the students (51.5%)
      had multimodal learning preferences. Among the unimodal group (48.5%), the most
      common mode was aural (24.0%), followed by kinesthetic (15.5%), reading-writing
      (8.0%), and visual (1.0%). There was a significant association between academic
      performance and the reading/writing learning style preference (P< 0.01).
      CONCLUSION: Multimodal learning styles were the most preferred. Among single-mode
      learning styles, the aural style was most common, followed by the kinesthetic
      style. Students with a reading/writing preference had better academic
      performance. The results of this study provide useful information for preparing a
      more problem-based curriculum with active learning strategies.

PMID- 29575849
TI  - Components of the item selection algorithm in computerized adaptive testing.
AB  - Computerized adaptive testing (CAT) greatly improves measurement efficiency in
      high-stakes testing operations through the selection and administration of test
      items with the difficulty level that is most relevant to each individual test
      taker. This paper explains the 3 components of a conventional CAT item selection
      algorithm: test content balancing, the item selection criterion, and item
      exposure control. Several noteworthy methodologies underlie each component. The
      test script method and constrained CAT method are used for test content
      balancing. Item selection criteria include the maximized Fisher information
      criterion, the b-matching method, the a-stratification method, the weighted
      likelihood information criterion, the efficiency balanced information criterion,
      and the Kullback-Leibler information criterion. The randomesque method, the
      Sympson-Hetter method, the unconditional and conditional multinomial methods, and
      the fade-away method are used for item exposure control. Several holistic
      approaches to CAT use automated test assembly methods, such as the shadow test
      approach and the weighted deviation model. Item usage and exposure count vary
      depending on the item selection criterion and exposure control method. Finally,
      other important factors to consider when determining an appropriate CAT design
      are the computer resources requirement, the size of item pools, and the test
      length. The logic of CAT is now being adopted in the field of adaptive learning,
      which integrates the learning aspect and the (formative) assessment aspect of
      education into a continuous, individualized learning experience. Therefore, the
      algorithms and technologies described in this review may be able to help medical
      health educators and high-stakes test developers to adopt CAT more actively and
      efficiently.

PMID- 29575850
TI  - Ultrasonography of benign vulvar lesions.
AB  - With the increasing applications of ultrasonography in the field of dermatology,
      this imaging modality can be extended to identify and characterize common vulvar
      lesions, with a particular focus on their location, size, vascularity, and
      content. This pictorial essay provides an introduction to vulvar ultrasonography,
      including technical considerations, ultrasonographic anatomy, and the
      ultrasonographic appearances of some vulvar conditions.

PMID- 29575851
TI  - Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in
      Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer
      Consortium (KLCC-13-01).
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of cancer with
      poor prognosis. As individual cancers exhibit unique mutation patterns,
      identifying and characterizing gene mutations in NSCLC might help predict patient
      outcomes and guide treatment. The aim of this study was to evaluate the clinical
      adequacy of molecular testing using next-generation sequencing (NGS) for small
      biopsy samples and characterize the mutational landscape of Korean patients with
      advanced NSCLC. METHODS: DNA was extracted from small biopsy samples of 162
      patients with advanced NSCLC. Targeted NGS of genomic alterations was conducted
      using Ion AmpliSeq Cancer Hotspot Panel v2. RESULTS: The median age of patients
      was 64 years (range, 32 to 83 years) and the majority had stage IV NSCLC at the
      time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had
      novel or hotspot mutations (range, 1 to 21 mutated genes). Mutations were found
      in 41 genes. Three of the most frequently mutated genes were TP53 (151, 93.2%),
      KDR (104, 64.2%), and epidermal growth factor receptor (EGFR; 69, 42.6%). We also
      observed coexistence of EGFR and other oncogene (such as KRAS, PIC3CA, PTEN, and
      STK11) mutations. Given that 69.6% (48/69) of EGFR mutant patients were treated
      with EGFR tyrosine kinase inhibitors, EGFR mutant status had higher prognostic
      ability in this study. CONCLUSIONS: These results suggest that targeted NGS using
      small biopsy samples is feasible and allows for the detection of both common and
      rare mutations in NSCLC.

PMID- 29575852
TI  - Streptococcus suis: a re-emerging pathogen associated with occupational exposure
      to pigs or pork products. Part II - Pathogenesis.
AB  - <i>Streptococcus suis</i> is a re-emerging zoonotic pathogen that may cause
      severe disease, mostly meningitis, in pigs and in humans having occupational
      contact with pigs and pork, such as farmers, slaughterhose workers and butchers.
      The first stage of the pathogenic process, similar in pigs and humans, is
      adherence to and colonisation of mucosal and/or epithelial surface(s) of the
      host. The second stage is invasion into deeper tissue and extracellular
      translocation of bacterium in the bloodstream, either free in circulation or
      attached to the surface of monocytes. If <i>S. suis</i> present in blood fails to
      cause fatal septicaemia, it is able to progress into the third stage comprising
      penetration into host's organs, mostly by crossing the blood-brain barrier and/or
      blood-cerebrospinal fluid barrier to gain access to the central nervous system
      (CNS) and cause meningitis. The fourth stage is inflammation that plays a key
      role in the pathogen esis of both systemic and CNS infections caused by <i>S.
      suis</i>. The pathogen may induce the overproduction of pro-inflammatory
      cytokines that cause septic shock and/or the recruitment and activation of
      different leukocyte populations, causing acute inflammation of the CNS.
      <i>Streptococcus suis</i> can also evoke - through activation of microglial
      cells, astrocytes and possibly other cell types - a fulminant inflammatory
      reaction of the brain which leads to intracranial complications, including brain
      oedema, increased intracranial pressure, cerebrovascular insults, and deafness,
      as a result of cochlear sepsis. In all stages of the pathogenic process, <i>S.
      suis</i> interacts with many types of immunocompetent host's cells, such as
      polymorphonuclear leukocytes, mononuclear macrophages, lymphocytes, dendritic
      cells and microglia, using a range of versatile virulence factors for evasion of
      the innate and adaptive immune defence of the host, and for overcoming
      environmental stress. It is estimated that <i>S. suis</i> produces more than 100
      different virulence factors that could be classified into 4 groups: surface
      components or secreted elements, enzymes, transcription factors or regulatory
      systems and transporter factors or secretion systems. A major virulence factor is
      capsular polysaccharide (CPS) that protects bacteria from phagocytosis. However,
      it hampers adhesion to and invasion of host's cells, release of inflammatory
      cytokines and formation of the resistant biofilm which, in many cases, is vital
      for the persistence of bacteria. It has been demonstrated that the arising by
      mutation unencapsulated <i>S. suis</i> clones, which are more successful in
      penetration to and propagation within the host's cells, may coexist in the
      organism of a single host together with those that are encapsulated. Both
      'complementary' clones assist each other in the successful colonization of host's
      tissues and persistence therein. <i>S. suis</i> has an open pan-genome
      characterized by a frequent gene transfer and a large diversity. Of the genetic
      determinants of <i>S. suis</i> pathogenicity, the most important are
      pathogenicity islands (PAI), in particular, a novel DNA segment of 89 kb length
      with evident pathogenic traits that has been designated as 89K PAI. It has been
      estimated that more than one-third of the <i>S. suis</i> virulence factors is
      associated with this PAI. It has been proved that the virulent <i>S. suis</i>
      strains possess smaller genomes, compared to avirulent ones, but more genes
      associated with virulence. Overall, the evolution of the species most probably
      aims towards increased pathogenicity, and hence the most significant task of the
      current research is an elaboration of a vaccine, efficient both for humans and
      pigs.

PMID- 29575853
TI  - Paget disease of bone among hospitalized patients in Poland.
AB  - INTRODUCTION: Paget's disease (PDB) is a focal disorder of bone remodeling that
      occurs commonly in older people with decreasing prevalence reported in European
      countries. This disease is most often asymptomatic, but it can cause a variety of
      medical complications resulting in considerable morbidity and reduced quality of
      life. There is little information regarding the epidemiology of PDB in Poland. To
      the best of the authors' knowledge, this is the first large epidemiological
      analysis of this disease in Poland. OBJECTIVE: The aim of this study was to
      analyze factors that may be related to the PDB epidemiology among hospitalized
      patients in Poland. MATERIAL AND METHODS: The analysis was conducted on the basis
      of population-based administrative data, taken from a Polish hospital morbidity
      study carried out by the National Institute of Public Health between January 2008
      - December 2014. RESULTS: Analyzed data covered 662 hospitalization records. The
      final study sample comprised 94 (41.8%) male and 131 (58.2%) female patients with
      first-time hospitalizations for PDB, with a significant predominance of females
      (P<0.02), and the predominance of patients living in urban (73%) than in rural
      areas (27%), P<0.001. The average age of the sample was 56.8 years (CI: 54.3
      59.3; SD 18.8; range 1-93 years). The number of PDB cases hospitalized in Poland
      significantly decreased during the analyzed period of time. CONCLUSIONS: PDB is a
      rare disease with decreasing trends observed among hospitalized patients in
      Poland. The study results may suggest the existence of environmental risk factors
      for the development of PDB.

PMID- 29575854
TI  - Differences in physical activity and nutritionand silhouette-related behaviours
      in male and female students in selected European countries.
AB  - INTRODUCTION: As indicated by the WHO, lifestyle plays a unique role in human
      health, which in turn is determined to a great extent by physical activity and
      nutrition. It must be borne in mind that physical activity should be systematic
      and regulated by an age-appropriate exercise intensity. All this indicates that
      learning about students' lifestyle, with a particular focus on physical activity
      is vital as it these young people who aspire to the role of the future elites.
      OBJECTIVE: The aim of the study is to evaluate the level of physical activity,
      nutrition- and silhouette-related behaviours of male and female students to
      assess the relationships between these variables in students from the Visegrad
      Group countries. MATERIAL AND METHODS: The study was conducted in 2015 and
      involved 2,497 students attending three undergraduate levels aged - x - 21,76,
      (SD-1,80) - 1,211 males (48.5%) and 1,286 females (51.5%). The IPAQ long-form and
      a questionnaire by the Polish Chief Sanitary Inspector were used. RESULTS:
      Physical activity was significantly higher in male than female students. An
      important relationship was observed among the larger number of consumed meals,
      level of physical activity, and silhouette-related behaviours in male students,
      which was not the case with females. However, there was an important correlation
      between physical activity in males and females who exercised to increase or
      decrease body weight (musculature), and took medications to increase body weight
      (musculature). CONCLUSIONS: Both males and females showed pro-health attitudes
      related to the level of physical activity and nutrition- and silhouette-related
      behaviours.

PMID- 29575855
TI  - Forms of expressing anger in hospitalised Ukrainian post-deployedTM service
      members.
AB  - INTRODUCTION: Military actions and injuries sustained make returning to ordinary
      life and everyday routine a challenge which soldiers need to face. Research on
      this subject shows that the consequences of post-traumatic stress extends
      further, beyond the victim's everyday life, resulting in health problems and
      problems with social relationships. OBJECTIVE: The aim was to gather knowledge of
      the ways of expressing anger in a group of hospitalized Ukrainian post-deployed
      servicemen. A research study was conducted concentrating on the two forms of
      managing anger, i.e. releasing or suppressing anger, and posing the following
      question: 'How are they manifested in the hospitalized Ukrainian combat veterans?
      MATERIALS AND METHOD: The study included 35 hospitalized soldiers who had taken
      part in military operations in Ukraine (age: 34.61+/-9.23; age range: 21-56 years
      of age). The research was conducted in the hospitals in Lutsk. Measurements were
      conducted with the use of certified psychological tests, i.e. Anger Expression
      Scale (AES), medical documentation and oral reports given by the persons
      conducting the study. RESULTS: The average value of the suppressed anger
      indicator was 31.57+/-6.23 (p<0.05); respective value of the released anger 24.37
      +/-6.34 (p<0.05). For released anger, results at the level of the upper quartile
      (Q3=28) and above were obtained by 28.57 % of the soldiers in the study, while in
      the case of repressed anger, the results obtained at the level of the upper
      quartile (Q3 = 36) and above that value were obtained by 34.27% of the
      soldiers/patients. CONCLUSIONS: The results obtained show that in the group of
      hospitalized patients/soldiers there is a higher level of repressed anger
      intensity than in the case of released anger. The study survey suggests that in
      their case expressing anger is usually a reaction to somebody's inappropriate-in
      their-eyes behaviour. Curbing anger takes on various forms, from trying not to
      express annoyance and/or rage, to trying to keep calm in spite of growing anger
      caused by other people's behaviours.

PMID- 29575856
TI  - Acceptance of illness by women with breast cancer.
AB  - INTRODUCTION: Despite great progress in the diagnostics and treatment, breast
      cancer still remains the most frequently diagnosed malignant cancer in women. The
      outcomes of cancer treatment depend, to a considerable extent, on the degree of
      acceptance of the illness. The objective of the study was determination of the
      level of acceptance of the disease among the examined women with breast cancer.
      MATERIAL AND METHODS: The study covered a group of 231 women who received
      treatment for breast cancer in the Rev. Bronislaw Markiewicz Subcarpathian
      Oncology Centre in Brzozow, south-eastern Poland, and conducted by the method of
      a diagnostic survey, using an author constructed questionnaire and the standard
      Acceptance of Illness Scale, adapted by Z. Juczynski. Statistical analyses were
      performed using the software IBM SPSS v. 21.0.0.1. The p values p<=0.05 were
      considered statistically significant. RESULTS: The mean level of acceptance of
      the illness in the examined group of women was 26.53 (SD = 7.71; Me = 26). The
      largest number of respondents (50.6%) obtained scores within the range of 20-29,
      according to the AIS Scale. From among the adopted variables, the level of
      acceptance of the illness significantly varied according to age and occupational
      activity. However, no such differences were confirmed according to the place of
      residence, marital status, education level, or the type of occupation performed.
      CONCLUSIONS: In the examined group of women, a mediocre level of acceptance of
      cancer was observed. The respondents' age and occupational situation exerted a
      significant effect on the level of acceptance of the illness. The results of the
      study should be considered as satisfactory because the number of women with a
      high level of acceptance of breast cancer was more than twice as high as those
      ones with a low acceptance of the disease.

PMID- 29575857
TI  - Ischemic cardiovascular disease in workers occupationally exposed to urban air
      pollution - A systematic review.
AB  - INTRODUCTION: Cardiovascular disease is the first cause of morbidity and
      mortality worldwide. Among several known risk factors, researchers also focus
      their attention on the chronic exposure to air pollution. There is much evidence
      that exposure to air pollution, especially to ultrafine particles, can damage the
      endothelium and can favour cardiovascular diseases in the general population.
      Occupational exposition could be an additive risk factor for the cardiovascular
      system. This article presents a scientific review of the linkage between
      occupational exposure to air pollution and ischemic heart disease. MATERIAL AND
      METHODS: A scientific review was undertaken, followed by PRISMA Statements.
      Observational studies were selected from several scientific databases, likesuch
      as Pubmed, Google Scholar, Nioshtic-2 and Reserchgate, searching for selected key
      words: police workers, professional drivers, mail carriers, filling station
      attendants, road cleaners, garage workers, motor vehicles and engine maintenance.
      All the key words were combined with "Boolean Operators" with the following
      words: cardiovascular (or cardiac) disease, cardiovascular function,
      cardiovascular system, ischemic heart disease, coronary disease, myocardial
      infarction. During the systematic research, the focus was on retrospective and
      prospective studies from January 1990 - December 2014. RESULTS: Both the
      retrospective and prospective studies showed an increased risk of ischemic heart
      disease in occupationally occupied people exposed to air pollution. Only one
      study presented a ly minor risk. CONCLUSIONS: The findings of this systematic
      review suggest a possible linkage between occupational exposure to urban air
      pollution, especially to motor exhaust and particulate, and ischemic heart
      disease.

PMID- 29575858
TI  - Effects of environmental pollution with aromatic hydrocarbons on endocrine and
      metabolic functions of the human placenta.
AB  - INTRODUCTION: Phenol and 1-hydroxypyrene are biological markers of exposure to
      polycyclic aromatic hydrocarbons (PAH) that have certain negative effects on
      parenchymal organs such as the human placenta. The literature presents only few
      reports regarding the effects of elevated PAH levels on the functions of the
      human placenta. OBJECTIVE: The aim of the work is to assess the effects of
      elevated PAH levels in excreted urine on the endocrine and metabolic functions of
      the human placenta obtained from a normal pregnancy. MATERIAL AND METHODS: Tissue
      material from 50 afterbirths from Plock constituted a study group, whereas 50
      afterbirths from Kutno constituted a control group. Immunohistochemical reactions
      with the peroxidase method using LSAB kits (DAKO, Denmark) were performed. The
      extent and intensity of reactions were analysed. The levels of phenols and 1
      hydroxypyrene in the excreted urine of pregnant women (undergoing delivery) were
      detected using gas chromatography and colorimetry. The statistical analysis used
      the PQStat v.1.6.2 software; moreover, t-student and chi-square tests were used.
      Differences were considered to be significant at the significance level of 95%
      (p<0.05). RESULTS: The levels of phenol and 1-hydroxypyrene in the excreted urine
      were demonstrated to be statistically significantly higher in patients living in
      the area of Plock. Statistically lower expression of placental glutathione
      transferase and lower immunohistochemical demonstration of the placental
      phosphatase activity were observed in placentas from Plock. It has been
      demonstrated that the expression of the oestrogen receptor activity and placental
      gonadotropin is significantly higher in placentas from areas not contaminated
      with aromatic hydrocarbons (Kutno). CONCLUSIONS: The course of pregnancy in the
      environment with elevated levels of aromatic hydrocarbons leads to impaired
      placental functioning and reduced endocrine and metabolic activity of the
      placenta.

PMID- 29575859
TI  - Prevalence and socioeconomic determinants of leisure time physical activity among
      Polish farmers.
AB  - INTRODUCTION AND OBJECTIVE: The aim of this study is to evaluate the leisure time
      physical activity of Polish farmers in the context of meeting health-related
      recommendations, and to diagnose the social and economic determinants. The
      analysis concerned leisure and transportation activities of various intensity and
      sedentary time. MATERIAL AND METHODS: Farmers (n=153) aged over 18 were selected
      from a representative sample of Polish society (n=2039). In order to evaluate
      LTPA, the long version of the IPAQ was used. Statistically significant
      differences between the variables were tested using non-parametric tests. The
      relationship between the amount of exercise recommended by the WHO and studied
      socio-demographic criteria was assessed using log-linear analysis. RESULTS: The
      WHO health recommendations were met by 33.3% of farmers. Shares in LTPA (19.1%)
      and transportation (19.2%) significantly increased the chance of achieving these
      norms (OR=12.54 and 0.07, respectively). Along with age (>=40 years) and income
      (>=3000 PLN/?750) of Polish farmers, the risk of insufficient physical activity
      increased. Average MET-min/week for LTPA was 299.8+/-583.4 and transportation -
      521.2+/-1973.9. The average time of sitting during working days was 4.4+/-2.9,
      while it was 4.5+/-3.2 hrs/day during weekends. CONCLUSIONS: Health-promoting
      changes are necessary among Polish farmers, including an increase in the
      awareness of health benefits and the necessity of undertaking physically active
      ways of spending leisure time. It seems to be a legitimate action to develop a
      mini-tourist trail in the rural environment as a means of promoting physical
      activity also among women aged over 40, and from lower income groups, who are
      especially threatened by inactivity.

PMID- 29575860
TI  - Severity of work in opinions of rural women living in the Bieszczady region of
      south-eastern Poland.
AB  - OBJECTIVE: The objective of the study was recognition of the opinions of rural
      women living in the Bieszczady region of south-eastern Poland, concerning their
      perception of the degree of severity of work. The study was conducted among the
      inhabitants of the Cisna commune. MATERIAL AND METHODS: The basic research
      instrument was a questionnaire form containing 15 items. The study covered 101
      women living in the Cisna commune in the Bieszczady. The self-reported degree of
      work load on a farm was analyzed among women who were occupationally active, and
      those who were not occupationally active. The effect of assistance from family
      members on the severity of work perceived by women was considered. RESULTS: The
      women in the study focused on agro-tourism, a few of them were engaged in
      agricultural work and the majority worked in household gardens. The study showed
      that occupationally active women work considerably longer, on average, and are
      the most loaded, compared to those not engaged in occupational activity. The mean
      daily time devoted to duties on a farm did not significantly differ between
      occupationally active and non-active women, and amounted to 380 and 320 minutes,
      respectively. The majority of women who were non-active occupationally evaluated
      their household chores as the highest work load. In turn, the women who undertook
      occupational activity assessed them as most burdensome, despite great help from
      their family. The body positions assumed while performing field work were:
      standing, standing-bent-over, and walking. The mean evaluations of work load
      while standing and standing-bent-over did not significantly differ, but affected
      the work load among women who, however, could not assess the severity of their
      work resulting from the body position assumed.

PMID- 29575861
TI  - Study on changing patterns of reproductive behaviours due to maternal features
      and place of residence in Poland during 1995-2014.
AB  - INTRODUCTION: The sharp decline in the total fertility rate in Poland coincided
      with broader socio-economic changes, which resulted in its reduction to the
      lowest level observed among the countries of Central and Eastern Europe.
      <b>Objective.</b> The aim of the study was to investigate and evaluate the
      changing patterns of reproductive behaviour in rural and urban areas, depending
      on the demographic and socio-economic features in Poland. MATERIAL AND METHODS:
      Information about live births in Poland in the years 1995-2014 were obtained from
      the Central Statistical Office. Registered cases of live births in rural and
      urban areas were analyzed considering the maternal features (age, marital status,
      main source of income). To evaluate the changes in fertility and comparisons
      between rural and urban areas, Joinpoint Regresssion was used. RESULTS: In 1995
      2014, a shift in the age of highest fertility from 20-24 years to 25-29 years was
      observed. This occurred at the same time as a reduction in the fertility rate per
      1,000 women aged 15-29 years, more pronounced in rural areas (95.8 to 60.0) than
      in urban areas (63.4 to 51.5), while in women aged 30-49 years, a faster increase
      in fertility was observed in urban areas (16.4 to 32.0) than in rural areas (27.5
      29.2). Fertility trends between rural and urban areas differed significantly. A
      significant increase in live births for employed mothers was shown mainly in 2005
      2009; later, the growth rate in rural areas was slower and in urban areas the
      growth trend stopped. CONCLUSIONS: The postponement of births and reduction of
      fertility in women aged 15-29 requires active measures aimed at creating
      favourable conditions for achieving economic independence for the younger
      generation, as well as combining work with raising children, especially in rural
      areas. ABBREVIATIONS: APC - annual percentage change; AAPC - average annual
      percentage change; CSO - Central Statistical Office; TFR - total fertility rate.

PMID- 29575862
TI  - Dietary intake of antioxidants and fats in the context of coronary heart disease
      prevention among elderly people.
AB  - INTRODUCTION: Some literature data indicate that the proper intake of exogenic
      antioxidants from food and the proper intake of fats can offer significant
      protection against coronary heart disease. OBJECTIVES: The estimation of total
      antioxidant capacity of food intake on the basis of Dietary Antioxidant Index
      (DAI), together with an assessment of the contribution of particular food
      products in DAI, and the evaluation of consumption of all dietary fats and
      frequency of consumption of products that are a source of fats among elderly
      people in Krakow, Poland. MATERIAL AND METHODS: 143 persons (73 women and 70 men)
      aged 65-80 were studied. None of them was under specialist medical control,
      including cardiological control. DAI was investigated on the basis of the Food
      Frequency Questionnaire (FFQ) which included 145 food items. DAI was measured
      using the method by Benzi and expressed as FRAP (the ability to reduce
      Fe<sup>3+</sup> to Fe<sup>2+</sup>, measured in mMol/l). The daily intake of fats
      was estimated using the 24-h nutritional recall. The frequency of fats
      consumption was estimated with the usage of FFQ. For statistical analysis, chi2
      test was used. RESULTS: The mean value of DAI of all studied persons was 34.27 +
      11.72 mMol/l. The largest percentage of those studied had FRAP values in the
      range 25-35 mMol/l. The highest contribution in the total DAI value was found in
      fruit (36.2%), grains and cereal-based products (23.6%), and beverages (24.0%).
      The consumption of vegetables was on the fourth position (7.1%). The contribution
      of the remaining food products was low. The consumption of total fats (about
      70g/24h) and saturated fatty acids (14% of energetic value) exceeded the
      recommendations. The participation of mono-and polyunsaturated fatty acids in the
      diets was not in accordance with recommendations. The most frequently consumed
      fats were animal fats (sausages, butter) and cakes, but the consumption of
      vegetable oils, fish, nuts and seeds of oil plants was too low. CONCLUSIONS: The
      majority of elderly people made mistakes in their nutrition. The enrichment in
      natural antioxidants of the diets of elderly people and the normalization of
      their fats consumption should become an important element of primary and
      secondary prophylaxis of cardiovascular diseases.

PMID- 29575863
TI  - Assessment of health, functioning and disability of a population aged 60-70 in
      south-eastern Poland using the WHO Disability Assessment Schedule (WHODAS 2.0).
AB  - INTRODUCTION: There is a growing number of older people in Poland. This
      phenomenon results in the need to assess their problems related with functioning
      in everyday life. This is the first study conducted in Polish society which
      evaluates the prevalence of disability and limitations in functioning by means of
      WHODAS 2.0 questionnaire. OBJECTIVE: Evaluation of the health, functioning and
      disability of people aged 60-70 years living in south-eastern Poland. MATERIAL
      AND METHODS: The researched material was a randomly- selected sample of 1,000
      inhabitants of south-eastern Poland. The study was conducted by use of direct
      interviews applying the WHODAS 2.0. For the purpose of statistical analysis,
      measures of descriptive statistics and non-parametric tests of significance were
      used. RESULTS: Limitations in functioning were reported by 67.00% of participants
      aged 60-70 years, including 46.20% with a mild disability, 14.50% - moderate,
      6.30% - significant and extremely large disability. The highest level of
      disability occurred in areas related to participation in social life (mean =
      20.77), performing activities of daily living (mean = 17.42) and mobility (mean =
      17.23). A significantly higher level of disability (p <0.0001)was observed among
      unmarried people, the elderly and those with a greater number of chronic
      diseases. Higher level of physical activity was associated with lower disability
      level in the studied population (p<0.009). CONCLUSIONS: Regarding the studied
      population, it was found that many health problems become worse over the years.
      The state of health that deteriorates with age causes limitations in daily
      functioning, which lead to disability, activity limitations and participation in
      everyday life. The progressive ageing of the Polish population will cause an
      increasing demand for medical care and on the social services.

PMID- 29575864
TI  - Demographic characteristics and AMH levels in rural and urban women participating
      in an IVF programme.
AB  - OBJECTIVE: The primary aim of this preliminary study was to compare the IVF
      results of couples living in rural and urban areas. Additionally, the ovarian
      reserve parameters, such as AMH concentrations, were compared for the same
      groups. MATERIAL AND METHODS: The database of 1,265 women undergoing in vitro
      fertilization at the Invicta Fertility Center between May 2011-July 2012 were
      retrospectively analyzed. Women undergoing their first assisted reproductive
      technology cycle with ICSI, stimulated according to the long protocol, and whose
      AMH levels were measured using the same DSL kit, were selected. Ultimately, 651
      women were included in the study. All participants were categorized based on the
      area where they live: rural areas, small towns (<100,000 inhabitants) and large
      cities (>100,000). RESULTS: The mean age of the patients living in large cities
      was significantly higher in comparison to those from rural areas and small towns.
      A significantly higher pregnancy body mass index (BMI) was found in women from
      rural areas in comparison to the women living in small and large towns. Serum AMH
      and inhibin B concentrations, number of ampules of gonadotropins, and antral
      follicle count (AFC), did not differ significantly among the groups. The study
      showed no significant differences among the groups in terms of clinical pregnancy
      rate, both per started cycle and per embryo transfer. CONCLUSIONS: No significant
      differences were found in IVF outcomes among the groups inhabiting rural areas,
      small and large cities.

PMID- 29575865
TI  - Parity does not affect diabetes complications in women with type 1 diabetes.
AB  - INTRODUCTION: The problem concerning the impact of pregnancy on diabetic
      complications is a matter for discussion as there is some evidence suggesting
      that pregnancy may trigger development or progression of diabetic chronic
      complications. However, currently available data concerning this issue is still
      controversial. OBJECTIVE: The aim of the study was to evaluate the impact of
      obstetric history on the development of chronic microangiopatic and
      macroangiopatic complications in type 1 diabetic women. MATERIAL AND METHODS: The
      retrospective study comprised 226 white Caucasian type 1 diabetic women,
      including 190 parous and 36 nulliparous women. Anthropometric data, information
      concerning the course of the disease, including metabolic control and chronic
      complications, together with obstetric history, were registered. RESULTS: Parous
      women were older (p<0.001), but did not differ significantly regarding metabolic
      control in the course of the disease (p>0.05) and diabetes duration (p>0.05) from
      nulliparous subjects. There were no significant differences in the incidence
      (p>0.05) nor onset (p>0.05) of chronic diabetes complications between the groups.
      The number of deliveries did not correlate with either the incidence nor the
      onset of chronic complications. Longer DM duration at the moment of first
      delivery was related to the higher incidence of retinopathy (p<0.01), nephropathy
      (p<0.05) and neuropathy (p<0.001). CONCLUSIONS: The incidence of chronic diabetic
      complications does not differ between parous women and the subjects that were
      never pregnant, and is not related to the number of pregnancies.

PMID- 29575866
TI  - Gender, age, social disadvantage and quitting smoking in Argentina and Uruguay.
AB  - INTRODUCTION: Cessation of tobacco use has the potential to provide the greatest
      immediate benefits for tobacco control. Understanding the social determinants of
      smoking cessation is an essential requirement for increasing smoking cessation at
      the population level. The purpose of this study was to analyze the socio-economic
      dimensions associated with cessation success among adults in Argentina and
      Uruguay. MATERIAL AND METHODS: Data from the Global Adult Tobacco Survey (GATS),
      a cross-sectional, population-based, nationally representative survey conducted
      in Argentina (n=5,383) and Uruguay (n=4,833) was utilized. Univariable and
      multivariable logistic regression analyses with results being presented as odds
      ratios (OR) with 95% confidence intervals were applied to study differences among
      those respondents who sustained smoking abstinence (>=1 year) and those who
      continued smoking. RESULTS: The GATS study revealed that social gradients in
      tobacco quitting exist in Argentina and Uruguay. Being aged 25-34, particularly
      men in Uruguay, women in Argentina, low educated men in Argentina and having a
      lower asset index were associated with reduced odds for quitting. CONCLUSIONS:
      Factors that are driving differences in smoking cessation between diverse social
      groups in Latin America countries need to be considered when implementing
      relevant interventions to ensure tobacco control strategies work effectively for
      all population segments.

PMID- 29575867
TI  - Pregnancy planning and risk behaviours - a survey of women's experiences in
      selected European countries.
AB  - Pregnancy, a special period in a woman's life, should be preceded by proper
      preparation: a positive attitude to procreation, selection of optimum time for
      becoming pregnant, starting prevention of neural tube defects, restriction of the
      use of drugs, smoking, etc. The aim of this study was to determine the effect of
      pregnancy planning and antenatal classes on the use of stimulants during
      pregnancy. The study group included 877 women living in 7 European countries, and
      their experiences of planning pregnancy and substance abuse during pregnancy were
      investigated. In about a half (50.3%) of respondents the pregnancy was planned.
      The highest percentage of mothers who planned pregnancy was recorded in Poland
      and Bulgaria (about 76%). By contrast, in Germany the proportion of mothers who
      planned pregnancy was the lowest (46.2%). Surprisingly, they became pregnant
      despite very frequent use of birth control (96.7%). On average, 17.3% of
      respondents disclosed that they drank alcohol or coffee, smoked cigarettes or
      used psychoactive drugs during pregnancy. Among women who did not plan to be
      pregnant, the use of stimulants was recorded more often. However, pregnancy
      planning only slightly inclined women to stop the consumption of stimulants.
      Attendance at antenatal classes did not have any significant effect on the use of
      stimulants.

PMID- 29575868
TI  - How do patients perceive ambulatory psychiatric care and what are their needs?
AB  - INTRODUCTION AND OBJECTIVE: The quality of a doctor-patient relationship plays a
      vital role in all fields of medicine. In the case of psychiatry, this role is
      special as it provides the foundation for the whole therapeutic process. The aim
      of this study was to investigate the patient's perspective on psychiatric visits:
      patient's attitudes towards the psychiatrist, patient's view of the patient
      psychiatrist relationship, and the patient's needs and expectations from this
      relationship. MATERIAL AND METHODS: 615 psychiatric outpatients responded to the
      anonymous questionnaires connected with their attitudes towards the psychiatrist,
      evaluation of the doctor, and expectations from psychiatric care. The study was
      conducted in 10 out of 30 public centres for psychiatric care in north-eastern
      Poland. RESULTS: Generally, the patients liked and positively evaluated their
      psychiatrists. Patient's liking for the doctor was connected with the feeling
      that the doctor also liked the patient, as well as with perceiving the doctor as
      competent and willing to meet the patient. The longer the treatment with a
      particular psychiatrist and the rarer need to consult the doctor, the more
      positive attitude and evaluation of the doctor patients had. According to the
      patients, the most significant expectations were associated with both
      conversation with the doctor and receiving emotional support. CONCLUSIONS: The
      key phase for forming the patient-psychiatrist relationship was the first stage
      of cooperation in which patients created their attitudes towards the doctor
      without modifying them at further stages. Thus, further studies on learning and
      developing the ability to establish the relationship with the patient, inspiring
      the patient's trust and making psychiatric appointments comfortable from the
      first meeting, will be highly valuable.

PMID- 29575869
TI  - Volatile oil composition of <i>Carthamus Tinctorius</i> L. flowers grown in
      Kazakhstan.
AB  - INTRODUCTION: <i>Carthamus tinctorius L.</i> is commonly known as Safflower.
      <i>C. tinctorius</i> extracts and oil are important in drug development with
      numerous pharmacological activities in the world. This plant is cultivated mainly
      for its seed which is used as edible oil. For a long time, <i>C. tinctorius</i>
      has been used in traditional medicines as a purgative, analgesic, antipyretic and
      an antidote to poisoning. It is a useful plant in painful menstrual problems,
      post-partum haemorrhage and osteoporosis. OBJECTIVE: The subject of this study is
      the seeds of Kazakhstan species of 'Akmai' safflower, collected in the flowering
      stage in Southern Kazakhstan. Volatile oil was carry out to study the component
      composition of Kazakhstan 'AkMai' safflower flowers. MATERIALS AND METHOD: Pale
      yellow oily extracts were obtain by varying the process parameters. The volatile
      oil obtained by hydrodistillation of the petals <i>Carthamus tinctorius L.</i>
      was analyzed by gas chromatography/mass spectrometry (GC/MS). The yield of the
      oil was 0.175 % (v/w). 20 compounds representing 99.81% of the oil were
      characterized. The volatile oil was found to be rich in undecanoic acid, octane,
      2-nonen -1-ol, hexadecanal, dodecanal, dec-2-en-1-ol, nonanoic acid,
      tetradecanoic acid, 2 pentadecanone, 6,10,14-trimethyl, 1,2-benzenedicarboxylic
      acid, isobutyl-beta-phenylpropionate, 1.3-cyclohexadiene, myrtenoic acid,
      octadecanoic acid, heneicosanoic acid, 2(3H)-furanone, 4,4-dipropylheptane,
      hexcosane,1-eicosanol, as well as heptocosane. RESULTS: Volatile oil from the
      flowers of the Kazakhstan safflower species 'Ak-Mai' were investigated by GC/MS
      which allowed the detection of 20 compounds. Biologically active complex of the
      flower of the Kazakhstan safflower species 'Ak-Mai' was released for the first
      time by using this oil.

PMID- 29575870
TI  - How is the process of setting micronutrients recommendations reflected in
      nutrition policies in Poland? The case study of folate.
AB  - INTRODUCTION AND OBJECTIVE: Ensuring the adequate intake of micronutrients by
      populations is an important aspect of public health. This study aims to elucidate
      the process of setting nutrition recommendations and the development of
      subsequent policies associated with micronutrients in Poland by using the case
      study of folate. MATERIAL AND METHODS: The study was based on 13 interviews
      conducted between October 2010 - February 2011, and desk research comprising a
      review of the associated scientific literature and relevant documents, such as
      scientific opinions and reports of the meetings of scientific committees. The
      interviews were conducted within the EURRECA (EURopean micronutrient
      RECommendations Aligned) Network of Excellence in the frame of the European
      Union's 6th Framework Programme. RESULTS: Since 1997, the Experts Group of the
      Ministry of Health recommended that all women of childbearing age should consume
      folic acid as a supplement to prevent neural tube defects in their offspring. The
      fortification of foodstuffs with folic acid is not obligatory. This study
      describes the revision of the folate nutrient recommendation and the process by
      which strategies to increase the intake of this vitamin by the Polish population
      were identified. The institution responsible for the choice and implementation of
      folate policy is the Ministry of Health and the National Food and Nutrition
      Institute is responsible for setting/updating the nutrient recommendations.
      CONCLUSIONS: The current Polish nutrition recommendations for folate are
      consistent with the levels set by most other countries. The constant improvement
      of nutritional knowledge on folate among consumers, especially young women, is
      necessary.

PMID- 29575871
TI  - Regional differences in access to health care in Poland from the perspective of
      health care resources.
AB  - OBJECTIVE: To examine disparities in access to the public in Poland, in
      association of the resources of health care, socio-economic development of
      Provinces and their level of urbanization. MATERIAL AND METHODS: The Provinces
      were divided into four groups, using the quartile method, according to the
      urbanization and level of socio-economic development. The socio-economic
      development level was identified by the Human Development Index (HDI) for each
      Province. The urbanization level of each Province was determined by the Index of
      Urbanization (URBI). Disparities level to access to public health care was
      identified by taxonomic measure of accessibility (TMA), calculated using
      resources of health care data. TMA index was compared in the different regions,
      depending on the level of HDI and URBI. RESULTS: There was no linear relationship
      between accessibility to public healthcare and socio-economic development of each
      tested region, nor between accessibility to public health care in the Provinces
      and their urbanization level. During the study, the correlation between the TMA
      and HDI and URBI alsdo produced a negative result. CONCLUSIONS: An insufficient
      number of physicians and the limited value of contracts within the public health
      service may cause a drop in the availability of the public medical service
      sector, regardless of regional level of urbanization and socio-economic
      development.

PMID- 29575872
TI  - Premature atherosclerosis after treatment for acute lymphoblastic leukemia in
      childhood.
AB  - INTRODUCTION: Late cardiovascular complications are the leading causes of
      morbidity and mortality in patients treated for common malignancies of childhood.
      Late cardiotoxicity include increased development of atherosclerosis and
      atherosclerosis - related diseases. An evaluation of the endothelium can be made
      based on the measurement of endothelium-derived blood vasoactive factors, such as
      cytokines and adhesion molecules. Their elevated serum levels may serve as
      sensitive indicators of early atherosclerotic lesions in high risk patients.
      Currently, assessment of common carotid intima-media thickness has emerged as one
      of the more powerful tools for evaluation of subclinical atherosclerosis. The
      purpose of this study was to compare these parameters between patients after
      antineoplatic treatment compared to persons not exposed to such factors. MATERIAL
      AND METHODS: Early progression of atherosclerotic disease was evaluated in 64
      survivors treated for Acute Lymphoblastic Leukaemia (ALL) in childhood, and in a
      control group of 36 healthy volunteers. Blood serum concentrations of selected
      new biomarkers, indicative of endothelial damage and inflammatory activity, were
      measured, including intercellular adhesion molecule-1 (sICAM-1), endothelial
      leukocyte adhesion molecule-1 (E-selectin), thrombomodulin (TM), interleukin 6
      (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The common carotid
      intima-media thickness (IMT) was also assessed via ultrasound examination.
      RESULTS: Significantly higher blood concentrations of sICAM-1 adhesive molecule
      (229.3+/-62.2 ng/mL vs. 199.9 +/- 63.3 ng/ mL, p=0.0072) and IL-6 (2.1 +/- 2.7
      pg/mL vs. 1.9 +/- 3.6 pg/mL, p=0.0414) were found in ALL survivors compared with
      control subjects. Concentration of hs-CRP was also higher in the ALL group: 1.3
      +/- 2.2 ug/mL vs. 0.6 +/- 0.9 ug/mL. This difference was close to statistical
      significance (p=0.0599). The mean IMT values for right and left carotid arteries
      were higher in ALL patients after antineoplastic therapy, compared with healthy
      subjects (IMT-R 0.056+/-0.008 mm vs. 0.052+/-0.003 mm; p=0.0021; IMT-L 0.057+/
      0.009 mm vs. 0.052+/-0.003 mm; p=0.0051). CONCLUSIONS: Survivors of childhood ALL
      in the examined group demonstrated elevated concentrations of selected new
      biomarkers and increased IMT values, compared to controls, which may confirm the
      occurrence of endothelial injuries in blood vessels. This study indicates that
      subjects treated for childhood malignancy are at a higher risk of prematurely
      developing atherosclerosis.

PMID- 29575873
TI  - Prevalence of dental erosion among 18-year-old adolescents in the borderland
      districts of Lviv (Ukraine) and Lublin (Poland).
AB  - INTRODUCTION AND OBJECTIVE: Recent epidemiological studies have shown an
      association between dental erosion occurrence and changes in lifestyle and
      dietary habits in both developed and developing countries, and now affects
      different regions of the world. Furthermore, in current literature, studies have
      shown that the prevalence of erosive tooth wear has increased particularly among
      the younger population. The aim of the study was to assess the prevalence and
      severity of erosive tooth wear among 18-year-old adolescents in the districts of
      Lviv (Ukraine) and Lublin (Poland). MATERIAL AND METHODS: College students (254
      subjects) aged 18, living in the Lviv and Lublin districts were examined. Erosive
      lesions presented in the teeth were assessed on the basis of the BEWE (Basic
      Erosive Wear Examination) index. RESULTS: Among the 137 patients living in the
      Lublin district, 70 were females and 67 were males, while in the Lviv district,
      60 women and 57 men were examined. In both districts, the following numbers of
      rural patients were examined: 66 in Lublin district and 56 in Lviv district; for
      urban inhabitants, the numbers were 71 in Lublin and 61 in Lviv. Analysing the
      BEWE values, it was noted that higher BEWE values, and resulting from them
      significant differences were observed in both male and female groups living in
      Lublin, compared with Lviv inhabitants. Based on clinical examination and
      statistical analysis, the occurrence of lesions of an erosive character in at
      least one sextant were observed in 59.85% of patients from Lublin district, and
      in 42.74% of patients from Lviv district. CONCLUSIONS: On the basis of the
      conducted study in the Polish and Ukrainian groups of 18-year-old adolescents
      living on the borderland, it can be stated that dental erosion is a problem
      noticeable in both groups of cohorts, but with higher prevalence in the Lublin
      district.

PMID- 29575874
TI  - Influence of growth hormone therapy on selected dental and skeletal system
      parameters.
AB  - INTRODUCTION: Growth hormone deficiency (GHD) is one of the main indications for
      growth hormone therapy. One characteristic of this disease is bone age delay in
      relation to the chronological age. Pituitary dysfunction negatively affects the
      growth and development of the jaws and teeth of the child. The secretion of
      endocrine glands regulates growth, development, and gender differentiation. It
      also controls the growth of bones and teeth, regulates metabolism of calcium and
      phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine
      system is played by the pituitary gland which is responsible for the production
      of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on
      the growth and development of long bones in the body, and may have an adverse
      effect on the development of maxilla, mandible and dentition of a child. There is
      some information in the literature that dental age is delayed in short stature
      children; the replacement of deciduous teeth by permanent teeth is also delayed,
      and newly erupted permanent teeth often require orthodontic treatment. Applying
      hormonal therapy positively affects the process of replacement of dentition [2,
      3, 4, 5, 6]. OBJECTIVES: The aim of the study was to assess bone and dental age,
      as well as analyze the state of dentition in children diagnosed with GH
      deficiency treated with growth hormone, depending on the duration of treatment.
      MATERIAL AND METHODS: The study material consisted of 110 children (27 males, 83
      females), hospitalized for somatotropin hypopituitarism in the Department of
      Paediatric Endocrinology and Diabetology at the Medical University of Lublin,
      Poland. The mean birth age was 13 years (156 months) with a standard deviation of
      2 years and 6 months (30 months). 47 children (43%) started treatment with the
      growth hormone (group starting treatment) and 63 children (57%) whose treatment
      was started 2-3 years previously (group in the course of treatment). The control
      group consisted of 41 generally healthy children (15males, 25 females) with ENT
      problems, such as hypoacusis and a condition after nasal injury, hospitalized in
      the Department of Paediatric Otolaryngology at the Medical University of Lublin,
      Poland. The mean age was 11 years and 5 months (137 months) with standard
      deviation of 2 years and 5 months (29 months). Informed consent was obtained from
      the parents. The study was approved by the Bioethical Committee at the Medical
      University of Lublin (Resolution No. KE-0254 /216 /2012).

PMID- 29575875
TI  - Assessment of the efficacy of ofatumumab in patients with chronic lymphocytic
      leukaemia treated in the Department of Haematooncology and Bone Marrow
      Transplantation of the Medical University in Lublin - Prelimary results.
AB  - INTRODUCTION: Despite significant recent advances in the treatment of chronic
      lymphocytic leukaemia (CLL), most cases of the disease are still incurable.
      Treatment with monoclonal antibodies, such as ofatumumab, is one of the new
      therapeutic options. OBJECTIVE: Retrospective analysis of the efficacy of
      ofatumumab in patients with chronic lymphocytic leukaemia (CLL) treated in the
      Haematooncology and Bone Marrow Transplantation Department of the Medical
      University of Lublin, Poland, during 2011-2013. MATERIAL AND METHODS: The
      analysis included 5 patients (3 women and 2 men), aged 47-65, with Rai stage II
      IV CLL, after a few lines of treatment. Three patients received ofatumumab in
      monotherapy and 2 patients received ofatumumab in combination with
      cyclophosphamide (50 mg/day) and dexamethasone (40 mg/day). All patients included
      in the study were diagnosed with an active form of leukaemia with symptoms such
      as lymphocytosis or massive lymphadenopathy. RESULTS: All patients responded to
      the treatment. Within the first 8 weeks of the treatment, levels of white blood
      cells returned to normal in patients with baseline lymphocytosis (3 patients). An
      increase in platelet levels was reported in 3 patients. Haemoglobin levels were
      higher or comparable to the baseline values in all studied patients after the
      completion of immunotherapy. In the patient with massive lymphadenopathy and
      hepato- and splenomegaly, the size of the lymph nodes, spleen and liver decreased
      and neutrophil levels increased. Time of progression was 5-12 months, and in one
      patient partial remission has been maintained. The treatment was well-tolerated
      in most cases. Asymptomatic neutropenia and an infection with Candida glabrata
      were observed. CONCLUSIONS: Ofatumumab may be a new and safe therapeutic option
      for patients with CLL after a few lines of treatment.

PMID- 29575876
TI  - The effect of MLS laser radiation on cell lipid membrane.
AB  - INTRODUCTION: Authors of numerous publications have proved the therapeutic effect
      of laser irradiation on biological material, but the mechanisms at cellular and
      subcellular level are not yet well understood. OBJECTIVE: The aim of this study
      was to assess the effect of laser radiation emitted by the MLS M1 system
      (Multiwave Locked System) at two wavelengths (808 nm continuous and 905 nm
      pulsed) on the stability and fluidity of liposomes with a lipid composition
      similar to that of human erythrocyte membrane or made of phosphatidylocholine.
      MATERIAL AND METHODS: Liposomes were exposed to low-energy laser radiation at
      surface densities 195 mW/cm<sup>2</sup> (frequency 1,000 Hz) and 230
      mW/cm<sup>2</sup> (frequency 2,000 Hz). Different doses of radiation energy in
      the range 0-15 J were applied. The surface energy density was within the range
      0.46 - 4.9 J/cm <sup>2</sup>. RESULTS: The fluidity and stability of liposomes
      subjected to such irradiation changed depending on the parameters of radiation
      used. CONCLUSIONS: Since MLS M1 laser radiation, depending on the parameters
      used, affects fluidity and stability of liposomes with the lipid content similar
      to erythrocyte membrane, it may also cause structural and functional changes in
      cell membranes.

PMID- 29575877
TI  - Social functioning and the quality of life of patients diagnosed with
      schizophrenia.
AB  - INTRODUCTION: Schizophrenia to a considerably great degree impairs the social
      functioning of the persons affected in the spheres of interpersonal and
      occupational contacts, as well as self-care. It brings about serious cognitive,
      perceptual, motor and emotional deficits, inevitably leading to the social
      withdrawal of patients. This phenomenon may assume various forms, from the
      limitations in interpersonal relations, through narrowing these relations to only
      some circumstances, to the total cessation of social contacts. OBJECTIVE: The
      objective of the study is presentation of the most important problems related
      with social functioning and quality of life of patients diagnosed with
      schizophrenia, based on scientific studies conducted in Poland and worldwide.
      STATE OF KNOWLEDGE: The family of a schizophrenia patient exerts a great effect
      on the social functioning. While undertaking proper actions the family may become
      a co-therapist and significantly facilitate the patient's adjustment to life in
      society and his/her playing a specified role. Analysis of disorders in social
      functioning of patients with schizophrenia, in the context of social cognition,
      indicates the fact that these disorders have their source in the lack of
      capabilities for identification of own and other people's internal states,
      whereas mentalization is the essence of social cognition. CONCLUSIONS: Therapy,
      any psychosocial impact as well as rehabilitation, neutralizes the causes for
      patients' withdrawal from social life. Training of social skills is necessary
      which teaches patients to return to the situation when they would be able to
      function properly in their environment.

PMID- 29575878
TI  - Solec Spa - worldwide unique properties of Polish health resort in the service of
      rural medicine.
AB  - Solec Spa is health resort in south-eastern Poland. Its unique
      balneorehabilitation significance worldwide is determined by chloride-iodine
      sodium water with a high content of hydrogen sulphide. This water, classified as
      highly mineralized sodium-chloride (seltzer) sulphide, bromide, iodide, boron
      water, contains naturally approximately 0.9 g/l divalent sulphur compounds, which
      is the highest concentration noted among the mineral waters of the world. The
      effectiveness of the Solec waters is proven in: inflammatory and
      autoimmunological locomotor system diseases, degenerative joint disorders
      (osteoarthritis), post-traumatic and post-operative orthopedic diseases, skin
      diseases and allergic disorders. One of the main indications for balneotherapy in
      Solec Spa and Busko Spa is chronic brucellosis.

PMID- 29575879
TI  - Influence of socio-economic factors on emotional changes during the postnatal
      period.
AB  - OBJECTIVES: The aim of the study was to identify socio-economic factors that may
      influence the emotional changes which occur among new mothers in the first days
      postpartum. MATERIAL AND METHODS: A group of 541 women completed a questionnaire
      consisting of 30 multiple-choice questions, Edinburgh Postnatal Depression Scale
      (EPDS), and Hospital Anxiety and Depression Scale (HADS). Statistical
      calculations were performed with the use of Statistica v.10 and Cytel Studio v.
      9.0.0. RESULTS: The findings revealed the presence of factors which might
      increase the risk of mood disorders during the postpartum period. CONCLUSIONS:
      Women who demonstrate warning symptoms should be screened for postnatal emotional
      changes and mood swings during their hospitalization after delivery. EPDS seems
      to be a suitable tool for early detection of emotional disturbances.

PMID- 29575880
TI  - Modifiable lifestyle factors and ovarian cancer incidence in women.
AB  - INTRODUCTION: A correct diet plays an important role in the prevention of
      malignant tumours. The risk of the disease may be reduced by introducing a number
      of changes to the daily diet. The most important changes concern the amount of
      fat in the diet, dietary fibre, antioxidants in the food and the reduction of
      substances having a significant impact on the development of malignant tumours.
      OBJECTIVE: The aim of the study is to analyse the role of selected modifiable
      lifestyle factors affecting the development of ovarian cancer. MATERIAL AND
      METHODS: The study covered healthy women and women with diagnosed ovarian cancer.
      A total of 850 women aged between 21-84 were studied. The study included women
      visiting the Gynaecology and Obstetrics Hospital of the University of Medical
      Sciences in Poznan, Poland, between 2011-2013. Patients recognized with malignant
      ovarian cancer were qualified into the study based on the histopathological
      examination of the material obtained during surgery. RESULTS: Respondents who
      consumed fruit and vegetables several times a week have the odds ratio OR = 0.29
      level; 95% CI 0.04-2.01 (p =.2085), compared to women not consuming fruit and
      vegetables at all. Consumption of 100 g of French fries and potato chips several
      times a week, results in a 2-fold increase in ovarian cancer. The OR for this
      group of women amounts to 2.06; 95% CI 0.53-7.99 (p=.2966). CONCLUSIONS: A diet
      rich in fruit and vegetables, including bulb vegetables, and grain products
      containing whole grains, should be introduced. It is recommended that the
      consumption of popular fast foods be eliminated.

PMID- 29575881
TI  - Prevalence of <i>Borrelia burgdorferi</i> in ticks removed from skin of people
      and circumstances of being bitten - research from the area of Poland, 2012-2014.
AB  - INTRODUCTION: During feeding, the tick sucks blood from the host along with the
      pathogens that are in the blood, simultaneously exchanging its own pathogens with
      the host. Humans can also be a host. It is important to understand the most
      typical circumstances in which people might become infected with<i> Borrelia
      burgdorferi</i>. This knowledge will help to prepare health education programmes
      aimed at the prevention of Lyme disease and other tick-borne diseases. OBJECTIVE:
      The aim of the study was to determine the percentage of ticks infected with
      <i>Borrelia burgdorferi</i> sensu lato, depending on the circumstances of getting
      bitten. MATERIAL AND METHODS: The research material consisted of ticks acquired
      from people who had been bitten, and questionnaires completed by these people.
      510 ticks were acquired from 257 females and 253 males. Following delivery of a
      tick for testing, the stage of its development was determined and a molecular
      assay of <i>Borrelia burgdorferi</i> DNA performed. RESULTS: A positive result of
      the nested-PCR test was obtained in 78 ticks, which represents 15.30% of all
      ticks. The infected ticks were collected from male (41 ticks - 52.56%) and female
      subjects (37 ticks - 47.44%). The biggest number of infected ticks were collected
      in autumn (54 ticks - 69.23%) and from people who had been into forests (44 ticks
      - 56.41%). Among the people from whom the infected ticks were acquired, the
      dominating group included persons over 16 years of age (53 persons - 67.95%) and
      children aged 0-5 years (16 persons - 20.51%). One in four infected ticks were
      acquired from the southwestern (20 ticks - 25.64%) and eastern regions of Poland
      (21 ticks - 26.92%). CONCLUSIONS: Infestation of ticks infected with Lyme disease
      spirochete in this study proved to be variable and depend on the season, the area
      of tick attack and the region in Poland. The results of the study clearly show
      that ticks infected with <i>Borrelia burgdorferi</i> inhabit all regions of
      Poland. The results are consistent with National Institute of Hygiene data which
      indicates that Lyme disease cases are recorded in all regions of Poland.

PMID- 29575882
TI  - Evaluation of the frequency of childhood hospitalization due to thermal injuries
      in the Provincial Polyclinical Hospital in Torun, Poland, 2007-2011.
AB  - INTRODUCTION: Burns constitute the most common and severe injuries suffered in
      childhood. OBJECTIVE: The study was aimed at providing a retrospective analysis
      of the etiology, location, extent and depth of burns, as well as treatment
      methods and length of hospital stay. MATERIAL AND METHODS: A retrospective
      analysis of 508 cases of children treated due to a thermal injury between 1
      January 2007 31 December 2011 was conducted at the Department of Paediatrics,
      Urology and Paediatric Surgery, Children's Hospital, L. Rydygier Provincial
      Hospital in Torun, Poland. RESULTS: The sample group included more boys (58.9%)
      than girls (41.1%). The most numerous group comprised children aged 1-2 years
      (44.5%). Burns were largely suffered at home (91.9%). Injuries were largely
      caused by thermal burns (99.2%). Half of the children sustained injury to one
      body area (51.4%), while every third sufferer (37.9%) was affected by burns to
      body parts prone to trigger shock. Burns up to 5% of the Total Body Surface Area
      (TBSA) were suffered by half (51.2%) of the children. Most of the patients
      underwent conservative treatment (89.4%). CONCLUSIONS: Burns were mostly suffered
      by children at 1-2 years of age, with boys prevailing over girls. Injuries were
      largely suffered at the child's family home, in the afternoon or evening, while
      the child was in the care of the parents. Scalds, caused by hot liquid,
      constituted the most frequent type of injury. The most numerous group of affected
      children comprised burns to limb areas, and thorax with limbs, with the TBSA of
      up to 5%. The great majority of the patients underwent conservative treatment,
      with a hospitalization period of up to 3 days.

PMID- 29575883
TI  - Relationships between bone mineral density and new indices of body composition in
      young, sedentary men and women.
AB  - INTRODUCTION: Data concerning the relationship between body fat and BMD are
      equivocal since both positive and negative effects have been noted. Recently, the
      index of fat mass (IFM) representing subjects with different body fat and similar
      lean mass and index of lean mass (ILM) representing subjects with different lean
      body mass and similar body fat, have been used to evaluate body composition
      effect on BMD in middle-aged women. This study aimed at determination of ILM and
      IFM association with BMD in young men and women. MATERIAL AND METHODS: A total of
      212 university students of Public Health (125 women and 87 men) participated in
      the study. Body composition was determined by the bioelectrical impedance method
      (BIA) using BC 418 MA equipment (Tanita Co., Japan). Fat mass and fat free mass
      were used to calculate ILM and IFM. Bone mineral density was measured on the
      wrist of the non-dominant hand using the DEXA method and EXA 3000 equipment (HFS
      Ltd., Korea). BMD was evaluated using Z-score, with values lower than -2.0
      indicating inadequate BMD for subject chronological age. RESULTS: Exclusively in
      women, IFM was markedly and positively correlated with Z-score (r=0.366,
      P<0.001). In both genders, a significant relationship was found between ILM and Z
      scores (r=0.420; p<0.001 and r=0.220; p<0.02 in men and women, respectively).
      Women with lower than median IFM but similar ILM, were characterized by
      significantly lower Z-scores vs. women with higher IFM (-1.016 vs. -0.512;
      p<0.001). Irrespective of gender, participants with higher ILM but similar IFM,
      were characterized by markedly higher Z-score vs. their counterparts with low
      ILM. CONCLUSIONS: The use of IFM and ILM in the present study, allowed the
      observation that in young adults lean body mass was associated with BMD,
      regardless of gender, while fat mass is significant for bone mineral density only
      in women.

PMID- 29575884
TI  - Responsiveness of people with moderate and significant intellectual disability to
      physical stimulation.
AB  - OBJECTIVE: The aim of the research was to verify whether intellectually disabled
      people are responsive to motor stimulation, and whether the specific physical
      exercises, besides traditional rehabilitation and occupational therapy, would
      result in physical fitness enhancement. MATERIAL AND METHODS: The research was
      carried out on 259 persons with moderate and significant intellectual disability,
      participants of occupational therapy workshops. They were divided into two
      groups: a control group that underwent traditional rehabilitation treatment and
      occupational therapy, and an experimental group that additionally performed
      feasible physical exercises for 10 months. Participants' body mass and height
      were measured to calculate their body mass index (BMI). Physical fitness was
      assessed with the Eurofit Special test and additional balance tests, at the
      beginning and at the end of the experiment. RESULTS: The results showed that the
      body mass of both men and women increased in the control group, and was reduced
      in the experimental group. The results of the physical fitness tests were more
      varied, in which the control group obtained similar results in the repeated
      measurements, and the experimental group significantly improved the initial
      results after 10 months of performing the feasible physical exercises.
      CONCLUSIONS: The applied physical exercises performed in the experimental group
      were effective because they caused body mass loss and significant improvement in
      physical fitness.

PMID- 29575885
TI  - Periodontal condition in patients of the specialist Outpatient Clinics at the
      Institute of Rural Health in Lublin, Poland.
AB  - INTRODUCTION: Periodontal disease is a chronic inflammation which, if remains
      untreated, can lead to the loss of teeth and supporting structures. Evidence data
      support the relationship of periodontal disease with the development and course
      of diseases such as heart attack, stroke, hypertension, chronic renal diseases,
      rheumatoid arthritis or diabetes. OBJECTIVE: The aim of the study was to conduct
      an assessment of periodontal status and periodontal needs in people from the
      rural environment who were patients of selected specialist outpatient clinics at
      the Institute of Rural Health in Lublin, Poland. MATERIAL AND METHODS: The
      examined population included 450 patients. The Community Periodontal Index of
      Treatment Needs, which is a measure of the assessment of the selected periodontal
      symptoms incidence, was used. The obtained data was discussed and analyzed with
      Chi-square test. RESULTS: The data obtained revealed that a healthy periodontium
      occurred only in 5.1% of respondents, tartar in 41.6%, pathological pockets of
      3.5-5.5 mm in 23.6%, and pockets deeper than 5.5 mm in 5.8% of patients. Most
      people with healthy periodontium were in the youngest age group. In the analyzed
      group, 7.1% of patients required specialized comprehensive periodontal treatment,
      and only 6.5% of the examined persons did not show any need for periodontal
      treatment. CONCLUSIONS: Patients of specialist clinics of the Institute of Rural
      Health who formed the analyzed group, had affected periodontium which required
      comprehensive periodontal treatment. The alarmingly high percentage of people
      over 55 years of age with advanced periodontopathy may translate into an
      increased risk of cause-and-effect incidence of systemic diseases.

PMID- 29575886
TI  - Health inequalities among students of lower secondary schools in Bytom, Poland.
AB  - INTRODUCTION AND OBJECTIVE: Poverty and low level of education pose the biggest
      threats to public health. Moreover, they generate inequalities in public
      healthThe aim of the study was to check if there are any inequalities in health
      among teenagers living in Bytom, Poland. MATERIAL AND METHODS: In 2011 and 2012,
      an epidemiological cross-sectional study was conducted on 1,099 students from
      lower secondary schools from Bytom. The students completed a questionnaire which
      was based on an earlier Health Behaviour in School-aged Children study (HBSC).
      Socio-Economic Status of teenagers (SES) was determined according to the Family
      Affluence Scale (FAS), the intensity of possible problems in the place of
      residence and on parents' education. Impact of SES on health self-assessment,
      asthma, pneumonia, bronchitis with addition to spinal deformities were also
      investigated. RESULTS: A good or very good level of health was declared by
      students from families representing a high level of FAS and residing in a more
      peaceful, less troubled neighbourhood. The highest level of asthma prevalence
      (10.9%) occurred among students from families with a low level of FAS. The
      students from families with high FAS were less affected by spinal deformities
      (34.6%). Students living in a troubled neighbourhood more often suffered from
      bronchial asthma, pneumonia, bronchitis and spinal deformities. CONCLUSIONS: The
      level of family affluence depends on the parents' education and all the analysed
      health problems occurred more frequently in children whose parents had completed
      at least general secondary education. A high economic standard of living and a
      peaceful neighbourhood determined good or very good health self-assessment among
      the surveyed students.

PMID- 29575887
TI  - Alcohol intoxication among adolescents and children in urban and rural
      environments - a retrospective analysis.
AB  - INTRODUCTION AND OBJECTIVE: Drinking alcohol by adolescents and children poses a
      risk of long-term psychological and sociological consequences, often leading to
      addiction in adulthood. A steady increase in the number of young people reaching
      for alcohol is worrying. The study analyzes the age and gender of the children,
      concentration of alcohol in the blood, depending on the origin of the youth
      (urban or rural). MATERIAL AND METHODS: The study was a retrospective analysis of
      402 patients hospitalized due to alcohol intoxication in the Department of
      Paediatrics at Medical University in Lublin, Poland between 2004 - 2013. RESULTS:
      During the study period a continuous increase in admissions of patients after
      alcohol consumption was observed: from 27 children in 2004 to 53 in 2012 and
      2013. The youngest patient hospitalized after drinking was 7.6 years old and came
      from the rural environment, the oldest 18 years old and came from the urban
      environment. In 2004 - 2007, boys dominated among children intoxicated with
      alcohol; since 2008, a slight prevalence of girls has been observed, especially
      in the urban environment. Among patients coming from the country, boys always
      predominated. In the study period there was noted a similar number of children
      consuming alcohol from rural and urban environments. CONCLUSIONS: The results
      suggest the need to introduce appropriate educational programmes in schools to
      prevent the consumption of alcohol at a young age.

PMID- 29575888
TI  - Encapsulation of OZ439 into Nanoparticles for Supersaturated Drug Release in Oral
      Malaria Therapy.
AB  - Malaria poses a major burden on human health and is becoming increasingly
      difficult to treat due to the development of antimalarial drug resistance. The
      resistance issue is further exacerbated by a lack of patient adherence to multi
      day dosing regimens. This situation motivates the development of new antimalarial
      treatments that are less susceptible to the development of resistance. We have
      applied Flash NanoPrecipitation (FNP), a polymer-directed self-assembly process,
      to form stable, water-dispersible nanoparticles (NPs) of 50-400 nm in size
      containing OZ439, a poorly orally bioavailable but promising candidate for single
      dose malaria treatment developed by Medicines for Malaria Venture (MMV). During
      the FNP process, a hydrophobic OZ439 oleate ion paired complex was formed and was
      encapsulated into NPs. Lyophilization conditions for the NP suspension were
      optimized to produce a dry powder. The in vitro release rates of OZ439
      encapsulated in this powder were determined in biorelevant media and compared
      with the release rates of the unencapsulated drug. The OZ439 NPs exhibit a
      sustained release profile and several-fold higher release concentrations compared
      to that of the unencapsulated drug. In addition, XRD suggests the drug was
      stabilized into an amorphous form within the NPs, which may explain the
      improvement in dissolution kinetics. Formulating OZ439 into NPs in this way may
      be an important step toward developing a single-dose oral malaria therapeutic,
      and offers the possibility of reducing the amount of drug required per patient,
      lowering delivery costs, and improving dosing compliance.

PMID- 29575889
TI  - Layered Halide Double Perovskites: Dimensional Reduction of Cs2AgBiBr6.
AB  - We investigate the consequences of dimensional confinement on halide double
      perovskites by synthesizing two-dimensional analogues of the recently reported
      three-dimensional double perovskite Cs2AgBiBr6. The layered perovskites
      (BA)4AgBiBr8 (1) and (BA)2CsAgBiBr7 (2) (BA = CH3(CH2)3NH3+) feature metal-halide
      sheets of mono and bilayer thickness, respectively, where the ordered double
      perovskite lattice is partitioned by organic cations. Electronic structure
      calculations indicate that the indirect bandgap of Cs2AgBiBr6 becomes direct when
      the infinitely thick inorganic lattice is reduced to monolayer thickness.
      Calculations on model systems allow us to separate the effects of dimensional
      reduction from those of the accompanying structural distortions in the inorganic
      sublattice. Detailed optical characterization shows that the photophysical
      properties of 1 and 2 are markedly different than those of their well-studied
      lead-halide analogs. Hybrid layered derivatives of double perovskites
      substantially expand on the substitutional flexibility of halide perovskites to
      encompass greater compositional and electronic diversity.

PMID- 29575890
TI  - Molecular Oxygen Formation in Interstellar Ices Does Not Require Tunneling.
AB  - The formation of molecular oxygen in and on amorphous ice in the interstellar
      medium requires oxygen diffusion to take place. Recent experiments suggest that
      this process involves quantum tunneling of the oxygen atoms at sufficiently low
      temperatures. Fitting experimental diffusion rates between 6 and 25 K to an
      expression that accounts for the roughness of the surface yields excellent
      agreement. The molecular dynamics of adsorbed oxygen is characterized by rapid
      intrasite dynamics, followed by intersite transitions over distances of ~10 A.
      Explicit simulations using a realistic free-energy surface for oxygen diffusion
      on amorphous ice down to 10 K show that quantum tunneling is not required for
      mobility of adsorbed oxygen. This is confirmed by comparing quantum and classical
      simulations using the same free-energy surface. The ratio of diffusional and
      desorption energy Edif/ Edes = 275/1082 ~ 0.3 is at the lower end of typically
      used values but is still consistent with the assumptions made in models for
      interstellar chemistry.

PMID- 29575891
TI  - A New Anisotropic Dirac Cone Material: A B2S Honeycomb Monolayer.
AB  - Different from the isotropic Dirac cones existing in other two-dimensional (2D)
      materials, anisotropic Dirac cones have the merit of anisotropic carrier mobility
      for applications in direction-dependent quantum devices. Motivated by the recent
      experimental finding of an anisotropic Dirac cone in borophene, here we report a
      new 2D anisotropic Dirac cone material, B2S monolayer, identified by using a
      global structure search method and first-principles calculation combined with a
      tight-binding model. The B2S monolayer is found to be stable mechanically,
      thermally, and dynamically and exhibits an anisotropic Dirac cone exactly at the
      Fermi level, showing a Fermi velocity of 106 m/s in the same order of magnitude
      as that of graphene. Moreover, B2S monolayer is the first anisotropy Dirac cone
      material with a pristine honeycomb structure stabilized by S in free-standing
      conditions where each atom has four valence electrons on average being
      isoelectronic to C. This study would expand the Dirac cone material family with
      new features.

PMID- 29575892
TI  - Hidden Gratings in Holographic Liquid Crystal Polymer-Dispersed Liquid Crystal
      Films.
AB  - Dynamic diffraction gratings that are hidden in the field-off state are
      fabricated utilizing a room-temperature photocurable liquid crystal (LC) monomer
      and nematic LC (NLC) using holographic photopolymerization techniques. These
      holographic LC polymer-dispersed LCs (HLCPDLCs) are hidden because of the
      refractive index matching between the LC polymer and the NLC regions in the as
      formed state (no E-field applied). Application of a moderate E-field (5 V/MUm)
      generates a refractive index mismatch because of the NLC reorientation (along the
      E-field) generating high-diffraction efficiency transmission gratings. These
      dynamic gratings are characterized by morphological, optical, and electrooptical
      techniques. They exhibit a morphology made of oriented LC polymer regions
      (containing residual NLC) alternating with a two-phase region of an NLC and LC
      polymer. Unlike classic holographic polymer-dispersed LC gratings formed with a
      nonmesogenic monomer, there is index matching between the as-formed alternating
      regions of the grating. These HLCPDLCs exhibit broad band and high diffraction
      efficiency (~90%) at the Bragg angle, are transparent to white light across the
      visible range because of the refractive index matching, and exhibit fast response
      times (1 ms). The ability of HLCPDLCs not to consume electrical power in the off
      state opens new possibilities for the realization of energy-efficient switchable
      photonic devices.

PMID- 29575893
TI  - Superior Growth Rates in Broilers Fed Wheat with Low In Vitro Feed-Xylanase
      Inhibition.
AB  - Grain-batch variation in xylanase-inhibitor levels may account for variations in
      the efficacy of feed xylanase supplementation. This would make inhibition an
      important quality parameter in the routine analysis of feedstuffs. Two analytical
      procedures for testing feedstuffs against specific xylanases were researched: the
      high-throughput viscosity-pressure assay (ViPr) and the extraction-free remazol
      brilliant-blue-beechwood-xylan (RBBX) assay. Thirty-two wheat cultivars were
      analyzed for inhibition of a commercial xylanase, Ronozyme WX. Four cultivars
      were selected for a feeding experiment in which the growth of 1440 broilers from
      ages 7-33 days was monitored. The treatments resulted up to 7 % difference (day
      14) in broiler weight . The cultivar choice had an effect throughout the
      experiment ( p < 0.05). The performance ranking of the treatments corresponded
      better to xylanase inhibition than to crude-protein content or nonstarch
      polysaccharide content. Wheat-grain xylanase-inhibitor content is therefore a
      highly relevant quality parameter when broiler diets are supplemented with feed
      xylanase.

PMID- 29575894
TI  - Enantioselective Synthesis of Chiral-at-Cage o-Carboranes via Pd-Catalyzed
      Asymmetric B-H Substitution.
AB  - Carborane cage chirality is an outstanding issue of great interest as the
      icosahedral carboranes have wide applications in medicinal and materials
      chemistry. The synthesis of optically active carborane derivatives, whose
      chirality is associated with the substitution patterns on the polyhedron, will
      open new avenues to carborane chemistry. We report herein an efficient method to
      achieve chiral-at-cage arylation of o-carboranes with high regio- and
      enantioselectivities by a strategy of palladium-catalyzed asymmetric
      intramolecular B-H arylation and cyclization. This represents the first example
      of the enantioselective reaction on carboranes, providing an efficient way for
      the construction of chiral-at-cage compounds with new skeletons.

PMID- 29575895
TI  - Key Aroma Compounds in Smoked Cooked Loin.
AB  - Smoked cooked loin is one of the most popular meat products in Poland. In this
      study, key volatile compounds in this traditional Polish meat product were
      determined using gas chromatography-olfactometry and aroma extract dilution
      analysis (AEDA). In total, 27 odor-active volatile compounds were identified,
      with flavor dilution (FD) factors ranging from 4 to 1024, with the highest FD
      factors noted for 2-methoxyphenol, 2-methoxy-4-(prop-2-enyl)phenol, and 2-methoxy
      4-( E)-(prop-1-en-1-yl)phenol. Results of the quantitative analyses based on
      determinations with stable isotope dilution assays (SIDAs) and standard addition
      (SA), followed by calculations of the odor activity value (OAV), enabled
      identifying 24 of the volatile compounds responsible for flavor development in
      the analyzed smoked cooked loin. The highest OAVs were obtained for 2
      methoxyphenol, 2-methyl-3-furanthiol, 1-octen-3-one, and 2-methyl-3
      (methyldithio)furan.

PMID- 29575896
TI  - Free-Energy Landscape of the Dissolution of Gibbsite at High pH.
AB  - The individual elementary reactions involved in the dissolution of a solid into
      solution remain mostly speculative due to a lack of direct experimental probes.
      In this regard, we have applied atomistic simulations to map the free-energy
      landscape of the dissolution of gibbsite from a step edge as a model of metal
      hydroxide dissolution. The overall reaction combines kink formation and kink
      propagation. Two individual reactions were found to be rate-limiting for kink
      formation, that is, the displacement of Al from a step site to a ledge adatom
      site and its detachment from ledge/terrace adatom sites into the solution. As a
      result, a pool of mobile and labile adsorbed species, or adatoms, exists before
      the release of Al into solution. Because of the quasi-hexagonal symmetry of
      gibbsite, kink site propagation can occur in multiple directions. Overall, our
      results will enable the development of microscopic mechanistic models of metal
      oxide dissolution.

PMID- 29575897
TI  - Directional Transport of a Liquid Drop between Parallel-Nonparallel Combinative
      Plates.
AB  - Liquids confined between two parallel plates can perform the function of
      transmission, support, or lubrication in many practical applications, due to
      which to maintain liquids stable within their working area is very important.
      However, instabilities may lead to the formation of leaking drops outside the
      bulk liquid, thus it is necessary to transport the detached drops back without
      overstepping the working area and causing destructive leakage to the system. In
      this study, we report a novel and facile method to solve this problem by
      introducing the wedgelike geometry into the parallel gap to form a parallel
      nonparallel combinative construction. Transport performances of this structure
      were investigated. The criterion for self-propelled motion was established, which
      seemed more difficult to meet than that in the nonparallel gap. Then, we
      performed a more detailed investigation into the drop dynamics under squeezing
      and relaxing modes because the drops can surely return in hydrophilic combinative
      gaps, whereas uncertainties arose in gaps with a weak hydrophobic character.
      Therefore, through exploration of the transition mechanism of the drop motion
      state, a crucial factor named turning point was discovered and supposed to be
      directly related to the final state of the drops. On the basis of the theoretical
      model of turning point, the criterion to identify whether a liquid drop returns
      to the parallel part under squeezing and relaxing modes was achieved. These
      criteria can provide guidance on parameter selection and structural optimization
      for the combinative gap, so that the destructive leakage in practical productions
      can be avoided.

PMID- 29575898
TI  - Hydride Conformers of the Nitrogenase FeMo-cofactor Two-Electron Reduced State
      E2(2H), Assigned Using Cryogenic Intra Electron Paramagnetic Resonance Cavity
      Photolysis.
AB  - Early studies in which nitrogenase was freeze-trapped during enzymatic turnover
      revealed the presence of high-spin ( S = 3/2) electron paramagnetic resonance
      (EPR) signals from the active-site FeMo-cofactor (FeMo-co) in electron-reduced
      intermediates of the MoFe protein. Historically denoted as 1b and 1c, each of the
      signals is describable as a fictitious spin system, S' = 1/2, with anisotropic g'
      tensor, 1b with g' = [4.21, 3.76, ?] and 1c with g' = [4.69, ~3.20, ?]. A clear
      discrepancy between the magnetic properties of 1b and 1c and the kinetic analysis
      of their appearance during pre-steady-state turnover left their identities in
      doubt, however. We subsequently associated 1b with the state having accumulated
      2[e-/H+], denoted as E2(2H), and suggested that the reducing equivalents are
      stored on the catalytic FeMo-co cluster as an iron hydride, likely an [Fe-H-Fe]
      hydride bridge. Intra-EPR cavity photolysis (450 nm; temperature-independent from
      4 to 12 K) of the E2(2H)/1b state now corroborates the identification of this
      state as storing two reducing equivalents as a hydride. Photolysis converts
      E2(2H)/1b to a state with the same EPR spectrum, and thus the same cofactor
      structure as pre-steady-state turnover 1c, but with a different active-site
      environment. Upon annealing of the photogenerated state at temperature T = 145 K,
      it relaxes back to E2(2H)/1b. This implies that the 1c signal comes from an
      E2(2H) hydride isomer of E2(2H)/1b that stores its two reducing equivalents
      either as a hydride bridge between a different pair of iron atoms or an Fe-H
      terminal hydride.

PMID- 29575899
TI  - Sequential Hybrid Three-Dimensional Gas Chromatography with Accurate Mass
      Spectrometry: A Novel Tool for High-Resolution Characterization of Multicomponent
      Samples.
AB  - A novel sequential three-dimensional gas chromatography-high-resolution time-of
      flight mass spectrometry (3D GC-accTOFMS) approach for profiling secondary
      metabolites in complex plant extracts is described. This integrated system
      incorporates a nonpolar first-dimension (1Dnp) separation step, prior to a
      microfluidic heart-cut (H/C) of a targeted region(s) to a cryogenic trapping
      device, directly followed by the rapid reinjection of a trapped solute into a
      polar second-dimension (2DPEG) column for multidimensional separation (GCnp
      GCPEG). For additional separation, the effluent from 2DPEG can then be modulated
      according to a comprehensive 2D GC process (GC*GC), using an ionic liquid phase
      as a third-dimension (3DIL) column, to produce a sequential GCnp-GCPEG*GCIL
      separation. Thus, the unresolved or poorly resolved components, or regions that
      require further separation, can be precisely selected and rapidly transferred for
      additional separation on 2D or 3D columns, based on the greater separation
      realized by these steps. The described integrated system can be used in a number
      of modes, but one useful approach is to target specific classes of compounds for
      improved resolution. This is demonstrated through the separation and detection of
      the oxygenated sesquiterpenes in hop ( Humulus lupulus L.) essential oil and
      agarwood ( Aquilaria malaccensis) oleoresin. Improved resolution and peak
      capacity were illustrated through the progressive comparison of the tentatively
      identified components for GCnp-GCPEG and GCnp-GCPEG*GCIL methods. Relative
      standard deviations of intraday retentions (1 tR, 2 tR,, and 3 tR) and peak areas
      of <=0.01, 0.07, 0.71, and 7.5% were achieved. This analytical approach
      comprising three GC column selectivities, hyphenated with high-resolution TOFMS
      detection, should be a valuable adjunct for the improved characterization of
      complex plant samples, particularly in the area of plant metabolomics.

PMID- 29575900
TI  - Critical Factors in Determining the Heterolytic versus Homolytic Bond Cleavage of
      Terminal Oxidants by Iron(III) Porphyrin Complexes.
AB  - Heterolytic versus homolytic cleavage of the metal-bound terminal oxidant is the
      key for determining the nature of reactive intermediates in metalloenzymes and
      metal catalyzed oxygenation reactions. Here, we study the bond cleavage process
      of hypochlorite by iron(III) porphyrin complexes having 4-methoxy-2,6
      dimethylphenyl (1), 2,4,6-trimethylphenyl (2), 4-fluoro-2,6-dimethylphenyl (3), 2
      chloro-6-methylphenyl (4), 2,6-dichlorophenyl (5), and 2,4,6-trichlorophenyl (6)
      groups at the meso position. Oxoiron(IV) porphyrin pi-cation radical complexes
      (CompI) are characterized from the reactions of 1-4 with tetra- n-butylammonium
      hypochlorite (TBA-OCl) in dichloromethane at -80  degrees C, while oxoiron(IV)
      porphyrin complexes (CompII) are characterized for 5 and 6 under the same
      conditions. For all of 1-6, we find the formation of an epoxidation product in
      good yields from the catalytic reactions with TBA-OCl, suggesting heterolytic
      cleavages of the O-Cl bonds. CompI of 5 and 6 are reduced to the corresponding
      CompII by both chloride and hypochlorite, while CompI of 1-4 are not. The
      reduction reactions with hypochlorite are much faster than those with chloride.
      These results provide a mechanism where the O-Cl bond of the iron-bound
      hypochlorite is cleaved heterolytically to form CompI for all of 1-6, but the
      subsequent reduction reaction with remaining hypochlorite affords CompII for 5
      and 6. The E(OCl*/OCl-) value is the boundary to discriminate the identity of the
      final product: CompI or CompII. Thermodynamic analysis based on the redox
      potential is successfully applied for explaining the bond cleavage processes of
      the hypochlorite, hydroperoxide, and tert-butyl peroxide complexes.

PMID- 29575901
TI  - Smell of Stress: Identification of Induced Biochemical Pathways Affecting the
      Volatile Composition and Flavor Quality of Crops.
AB  - Recent research has shown that the biosynthesis of several key odorants is
      controlled by genes whose expression is altered or even induced by biotic or
      abiotic stress. These new findings provide a roadmap for improvement of flavor
      quality by the application of moderate, well-controlled stress. This strategy
      aims at reducing the flavor deficiencies in modern commercial varieties as a
      "green" alternative to genetic engineering. The workflow for a successful
      implementation of this approach, from the identification of key odorants by
      molecular science techniques to the investigation of mechanisms controlling their
      biosynthesis, is complex and calls for interdisciplinary research.

PMID- 29575902
TI  - Tailor-Made Self-Assemblies from Functionalized Amphiphiles: Diversity and
      Applications.
AB  - The objective of this feature article is to coalesce our recent advancements on
      different expressions of tailor-made supramolecular self-assemblies and to
      explore them as a function of molecular architecture. In the last decade, we have
      developed a library of elegant and simple functional amphiphilic small molecules,
      which have very interesting abilities to form diverse manifestations of
      supramolecular self-assemblies such as micelles, reverse micelles, vesicles,
      fibers, supramolecular gels, and so on. Each of the expressions of the self
      aggregated structures has its individual prominence and finds important
      applications in the fields of chemistry, physics, biology, and others. In this
      feature article, the major emphasis is mostly on how to attain precise control
      over the development of various well-defined supramolecular self-assemblies
      through the judicious design of low-molecular-weight amphiphiles. By tuning only
      the functional moieties of the amphiphilic structure, diverse supramolecular
      architectures can be constructed with task-specific applications. We expect that
      this article will provide a general and conceptual demonstration of various
      approaches to the development of different functional supramolecular systems and
      their prospective applications in numerous domains.

PMID- 29575903
TI  - Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites.
AB  - S-Fatty-acylation is the covalent attachment of long chain fatty acids,
      predominately palmitate (C16:0, S-palmitoylation), to cysteine (Cys) residues via
      a thioester linkage on proteins. This post-translational and reversible lipid
      modification regulates protein function and localization in eukaryotes and is
      important in mammalian physiology and human diseases. While chemical labeling
      methods have improved the detection and enrichment of S-fatty-acylated proteins,
      mapping sites of modification and characterizing the endogenously attached fatty
      acids are still challenging. Here, we describe the integration and optimization
      of fatty acid chemical reporter labeling with hydroxylamine-mediated enrichment
      of S-fatty-acylated proteins and direct tagging of modified Cys residues to
      selectively map lipid modification sites. This afforded improved enrichment and
      direct identification of many protein S-fatty-acylation sites compared to
      previously described methods. Notably, we directly identified the S-fatty
      acylation sites of IFITM3, an important interferon-stimulated inhibitor of virus
      entry, and we further demonstrated that the highly conserved Cys residues are
      primarily modified by palmitic acid. The methods described here should facilitate
      the direct analysis of protein S-fatty-acylation sites and their endogenously
      attached fatty acids in diverse cell types and activation states important for
      mammalian physiology and diseases.

PMID- 29575904
TI  - Degradation Chemistry and Stabilization of Exfoliated Few-Layer Black Phosphorus
      in Water.
AB  - Exfoliated black phosphorus (BP), as a monolayer or few-layer material, has
      attracted tremendous attention owing to its unique physical properties for
      applications ranging from optoelectronics to photocatalytic hydrogen production.
      Approaching intrinsic properties has been, however, challenged by chemical
      reactions and structure degradation of BP under ambient conditions. Surface
      passivation by capping agents has been proposed to extend the processing time
      window, yet contamination or structure damage rise challenges for BP
      applications. Here, we report experiments combined with first-principle
      calculations that address the degradation chemistry of BP. Our results show that
      BP reacts with oxygen in water even without light illumination. The reaction
      follows a pseudo-first-order parallel reaction kinetics, produces PO23-, PO33-,
      and PO43- with reaction rate constants of 0.019, 0.034, and 0.023 per day,
      respectively, and occurs preferentially from the P atoms locating at BP edges,
      which yields structural decay from the nanoflake edges in water. In addition, a
      negligible decay ratio (0.9 +/- 0.3 mol %) and preserved photocatalytic activity
      of BP are observed after storage in deoxygenated water for 15 days without
      surface passivation under ambient light. Our results reveal the chemistry of BP
      degradation and provide a practical approach for exfoliation, delivery, and
      application of BP.

PMID- 29575905
TI  - Efficient ZFN-Mediated Stop Codon Integration into the CCR5 Locus in
      Hematopoietic Stem Cells: A Possible Source for Intrabone Marrow Cell
      Transplantation.
AB  - We reported a simple genome editing approach that can generate human
      immunodeficiency virus-1 (HIV) coreceptor defective cells, which may be useful
      for latent viral eradication treatment. Samples of bone marrow leftover after
      diagnostic procedures and crude bone marrow from aviremic HIV patients were
      subjected to zinc finger nuclease-mediated stop codon insertion into chemokine
      receptor 5 (CCR5) loci. Locked nucleic acid-based polymerase chain reaction was
      used to estimate the amount of insertion in the expandable CD34+ cells. The
      results showed that about 0.5% of CD34+ cells carried stop codon insertions in
      CCR5 loci. Cells edited using this simple protocol have the potential to be
      infused back into the bone marrow.

PMID- 29575906
TI  - Simple, Inexpensive Classroom Experiments for Understanding Basic Gas Laws and
      Properties of Gases.
AB  - As educators, we are continually designing new methods and procedures to enhance
      learning. During this process, good ideas are frequently generated and tested,
      but the extent of such activities may not be adequate for a full manuscript.
      Nonetheless, the ideas may be quite beneficial in improving the teaching and
      learning of physiology. Illuminations is a column designed to facilitate the
      sharing of these ideas (illuminations). The format of submissions is quite
      simple: a succinct description of about one or two double-spaced pages (less
      title and authorship) of something you have used for the classroom, teaching,
      lab, conference room, etc. You may include one or two simple figures or
      references. Submit ideas for inclusion in Illuminations directly to the Associate
      Editor in charge, Stephen DiCarlo (sdicarlo@med.wayne.edu).

PMID- 29575907
TI  - Reliability and Validity Testing of the Quality of Life in Late-Stage Dementia
      Scale.
AB  - BACKGROUND/RATIONALE: This study tested the psychometric properties of the
      Quality of Life in Late-Stage Dementia (QUALID) Scale using Rasch analysis. The
      QUALID includes 11 items with a 5-point response scale. Scores range from 11 to
      55, and lower scores indicate higher quality of life (QoL). METHODS: Baseline
      data from a randomized clinical trial including 137 residents from 14 nursing
      homes were used. Psychometric testing included item mapping, evaluation of
      response categories, item reliability, construct validity based on INFIT and
      OUTFIT statistics, and convergent validity based on correlations between QoL and
      pain, agitation, depression, and function. RESULTS: The Cronbach alpha was .89.
      All the items except "appears physically uncomfortable" fit the model. There was
      a significant relationship between QoL and depressive symptoms ( r = .71, P =
      .001), pain ( r = .26, P = .01), physical function ( r = -.19, P = .03), and
      agitation ( r = .56, P = .001). The categories were appropriately used. Item
      mapping suggested a need for easier items.

PMID- 29575908
TI  - Serum matrix metalloproteinase-9 level as a biomarker for colorectal cancer: a
      diagnostic meta-analysis.
AB  - AIM: To comprehensively evaluate the diagnostic value of serum matrix
      metalloproteinase-9 (MMP-9) level for colorectal cancer (CRC). METHODS: Both of
      the relationships between MMP-9 level and CRC and the diagnostic value were
      evaluated from 12 eligible papers. RESULTS: The high MMP-9 level increased CRC
      risk. The estimated sensitivity and specificity were 69 and 68%, respectively,
      which signified that the diagnostic value was medium. Diagnostic odds ratio and
      the area under the receiver operating characteristic curve suggested MMP-9 level
      has a moderate diagnostic value in CRC. Additionally, the likelihood matrix
      indicated MMP-9 levels could be considered as a biomarker for the diagnosis of
      CRC. CONCLUSION: Patients with CRC have elevated MMP-9 levels, which is a
      potential biomarker for CRC diagnosis.

PMID- 29575909
TI  - Short Communication: Nucleoside Reverse Transcriptase Inhibitors with Reduced
      Predicted Activity Do Not Impair Second-Line Therapy with Lopinavir/Ritonavir or
      Darunavir/Ritonavir.
AB  - Second-line therapy randomized trials with lopinavir/ritonavir question the value
      of resistance testing to guide nucleoside reverse transcriptase inhibitor (NRTI)
      selection. In this study, we investigated the association between baseline drug
      resistance and treatment outcome after 104 weeks of second-line therapy with
      NRTIs and either darunavir/ritonavir or lopinavir/ritonavir in West-central
      Africa. We did an observational analysis of data from 387 individuals in a
      randomized, open-label 2LADY trial in Burkina Faso, Cameroon, and Senegal. We
      modeled the association between RTI drug resistance mutations (DRMs) and
      virological failure (VF) (viral load [VL] <50 copies/mL) at week 104 using
      logistic regressions. Covariates included baseline VL and CD4+ count,
      demographic, and adherence data. Overall, 193 (49.9%), 150 (38.8%), and 44
      (11.4%) individuals had, respectively, low/none (genotypic susceptibility score
      [GSS] <1), intermediate (GSS = 1), and high predicted NRTI activity (GSS >1) in
      their prescribed second-line regimen. The average number of DRMs by drug class,
      the proportion of individuals by GSS category, and the duration of first-line
      therapy were not associated with VF (p > .05). High VL at switch was the only
      consistent prognostic factor for VF after multivariate adjustment (p < .01).
      Suboptimal adherence, high predicted RTI activity, or low NRTI mutations were
      associated with VF (p < .05) when using higher end points for VF or in the
      intention-to-treat analysis. In conclusion, the use of RTIs with predicted
      reduced activity does not impair second-line protease inhibitor-based therapy.
      Therefore, HIV care in resource-limited settings should prioritize strategies to
      improve adherence and targeted VL testing over drug resistance testing for
      selecting NRTIs during a protease-based second-line switch.

PMID- 29575910
TI  - Short Communication: Characterization of a New HIV-1 Group N Isolate Originating
      from a Cameroonian Patient.
AB  - HIV-1 group N (HIV-1/N) remains rare and mainly restricted to Cameroon. In this
      study, we report a new HIV-1/N infected case identified during routine HIV
      screening activities in Yaounde. The genetic characterization of the near full
      length genome of this virus strain revealed that it is genetically distinct to
      all HIV-1/N described to date. However, the Vpu protein responsible for tetherin
      antagonism displayed the same amino acid substitutions (E15A, V19A, I25L, and
      V26L) as other HIV-1/N from Cameroon.

PMID- 29575911
TI  - T-2 mycotoxin treatment of newborn rat pups does not significantly affect nervous
      system functions in adulthood.
AB  - T-2 toxin is primarily produced by Fusarium sp. abundant under temperate climatic
      conditions. Its main harmful effect is the inhibition of protein synthesis.
      Causing oxidative stress, it also promotes lipid peroxidation and changes plasma
      membrane phospholipid composition; this may lead to nervous system alterations.
      The aim of the present study was to examine whether a single dose of T-2 toxin
      administered at newborn age has any long-lasting effects on nervous system
      functions. Rat pups were treated on the first postnatal day with a single
      intraperitoneal dose of T-2 toxin (0.2 mg/bwkg). Body weight of treated pups was
      lower during the second and third week of life, compared to littermates; later,
      weight gain was recovered. At young adulthood, behavior was tested in the open
      field, and no difference was observed between treated and control rats. Field
      potential recordings from somatosensory cortex and hippocampus slices did not
      reveal any significant difference in neuronal network functions. In case of
      neocortical field EPSP, the shape was slightly different in treated pups. Long
      term synaptic plasticity was also comparable in both groups. Seizure
      susceptibility of the slices was not different, either. In conclusion, T-2 toxin
      did not significantly affect basic nervous system functions at this dose.

PMID- 29575912
TI  - Intrathalamic connections shape spindle activity - a modelling study.
AB  - Spindle oscillations are generated predominantly during sleep state II, through
      cyclical interactions between thalamocortical and reticular neurons. Inhibition
      from reticular cells is critical for this activity; it enables burst firing by
      the de-inactivation of T-type Ca2+ channels. While the effect of different
      channelopathies on spindling is extensively investigated, our knowledge about the
      role of intrathalamic connections is limited. Therefore, we explored how the
      connection pattern and the density of reticular inhibitory synapses affect
      spindle activity in a thalamic network model. With more intrareticular
      connections, synchronous firing of reticular cells, and intraspindle burst
      frequency decreased, spindles lengthened. In models with strong intrareticular
      inhibition spindle activity was impaired, and a sustained 6-8 Hz oscillation was
      generated instead. The strength of reticular innervation onto thalamocortical
      cells played a key role in the generation of oscillations; it determined the
      amount of thalamocortical cell bursts, and consequently spindle length. Focal
      inputs supported bursts but affected only a few cells thus barely reinforced
      network activity, while diffuse contacts aided bursts only when a sufficient
      number of reticular cells fired synchronously. According to our study,
      alterations in the connection pattern influence thalamic activities and may
      contribute to pathological conditions, or alternatively, they serve as a
      compensatory mechanism.

PMID- 29575913
TI  - Age-related and function-dependent regional alterations of free L- and D
      aspartate in postembryonic chick brain.
AB  - D-aspartate (D-Asp) modulates adult neural plasticity and embryonic brain
      development by promoting cell proliferation, survival and differentiation. Here,
      developmental changes of the excitatory amino acids (EAAs) L-Glu, L-Asp and D-Asp
      were determined during the first postembryonic days, a time window for early
      learning, in selected brain regions of domestic chickens after chiral separation
      and capillary electrophoresis. Extracellular concentration (ECC) of EAAs was
      measured in microdialysis samples from freely moving chicks. ECC of D-Asp (but
      not L-EAAs) decreased during the first week of age, with no considerable regional
      or learning-related variation. ECC of L-Asp and L-Glu (but not of D-Asp) were
      elevated in the mSt/Ac in response to a rewarding stimulus, suggesting importance
      of Asp-Glu co-release in synaptic plasticity of basal ganglia. Potassium-evoked
      release of D-Asp, with a protracted transient, was also demonstrated. D-Asp
      constitutes greater percentage of total aspartate in the extracellular space than
      in whole tissue extracts, thus the bulk of D-Asp detected in tissue appears in
      the extracellular space. Conversely, only a fraction of tissue L-EAAs can be
      detected in extracellular space. The lack of changes in tissue D-Asp following
      avoidance learning indicates a tonic, rather than phasic, mechanism in the
      neuromodulatory action of this amino acid.

PMID- 29575914
TI  - Exogenous salicylic acid and cytokinin alter sugar accumulation, antioxidants and
      membrane stability of faba bean.
AB  - This research was conducted in a greenhouse to evaluate the effects of exogenous
      application of salicylic acid (SA) (1 mM) and 6-benzylaminopurine (BAP) (50 MUM)
      on physiological performance of faba bean (Vicia faba) under different levels of
      NaCl salinity (0, 4, 8 and 12 dS/m). The experiment was arranged as factorial on
      the bases of randomized complete block design in three replications. Leaf Na+
      content, root and leaf soluble sugars, antioxidant enzymes activities such as
      catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD) and lipid
      peroxidation increased, but K+, K+/Na+ and membrane stability index (MSI)
      decreased as a result of salt stress. However, foliar sprays of BAP and
      particularly SA reduced Na+ content and lipid peroxidation, while enhanced the K+
      content, K+/Na+, soluble sugars, antioxidant enzymes activities and MSI under
      different levels of salinity. It was, therefore, concluded that exogenous
      application of these growth regulators (GR) can considerably improve salt
      tolerance and physiological performance of faba bean.

PMID- 29575915
TI  - Transfer of egg white proteins and activation of proteases during the development
      of Anas platyrhynchos domestica embryo.
AB  - The route of egg white transfer into the yolk and the mechanisms underlying the
      digestion of egg proteins are unexplored in the fertilized egg of the duck, Anas
      platyrhynchos domestica. Here, we investigated the route(s) of egg white transfer
      and we determined the type of activated proteases during duck embryo development.
      Initially, we tested the electrophoretic patterns of egg proteins throughout
      development. Then, we used lysozyme as a reference protein to follow egg white
      transfer and we measured its activity. After that, we determined the type of
      activated proteases by employing different types of protease inhibitors. Several
      presumptive egg white protein bands appeared in different egg compartments. Also,
      lysozyme activity was detected chronologically on day 15 in the extraembryonic
      fluid, on day 17 in the amniotic and intestinal fluids and on day 19 in the yolk.
      Furthermore, acidic aspartic proteases seemed to be activated at hatch in the
      intestine and late in development in the yolk. Our results suggest that the main
      route of egg white transfer into the yolk is through the amniotic cavity and
      intestinal lumen. Also, the transferred egg white and endogenous yolk proteins
      are probably digested by the activated acidic proteases in the intestine and
      yolk.

PMID- 29575916
TI  - Factors affecting synonymous codon usage of housekeeping genes in Drosophila
      melanogaster.
AB  - Housekeeping genes (HK genes) are required for cell survival and the maintenance
      of basic cellular functions. The investigation of factors affecting codon usage
      patterns in HK genes of insects can help in understanding the molecular evolution
      of insects and aid the development of insect pest management strategies. In this
      study, we employed bioinformatics approaches to analyze the codon usage bias
      (CUB) of HK genes in the insect model organism, Drosophila melanogaster. A
      comparison of CUB between 1107 HK genes and 1084 high tissue specificity genes
      suggested that HK genes have higher CUB in D. melanogaster. In addition, we found
      that CUB inversely correlates with the non-synonymous substitution rate of HK
      genes. Therefore, we attempted to identify the factors that potentially influence
      the codon usage pattern of HK genes. Our results suggest that mutation pressure
      and natural selection highly correlate with CUB in the HK genes of D.
      melanogaster and that two topological properties of HK proteins (proportion of
      protein interacting length and protein connectivity) also correlate with CUB in
      the HK genes of D. melanogaster. This study provides insight into CUB in the HK
      genes of D. melanogaster, and the results can support future investigations of
      potential applications in agricultural and biomedical field.

PMID- 29575917
TI  - Morphology of the extraocular muscles (m. bulbi) in the pre-hatchling and post
      hatchling african black ostriches (struthio camelus domesticus L., 1758) (Aves:
      Struthioniformes).
AB  - The aim of the study was to describe the morphology and the development of the
      extraocular muscles (EOMs) in the pre-hatchling and post-hatchling African black
      ostrich. The study involved 50 birds aged between 28 days and 3 years. The EOMs
      were analyzed morphologically with respect to the location and length of the
      straight and oblique muscles and the third eyelid muscles, the length and breadth
      of their tendons as well as the distance and shape of the muscle tendon
      insertions at the corneal limbus. A histological and histometric analysis were
      also carried out. The greatest increase in the length of the EOMs was noted in
      groups III-V. A marked increase in the length of the tendons of the dorsal
      straight muscle was found in groups II and III, in the tendons of the nasal
      straight muscle in groups IV and V, in the tendons of the dorsal oblique muscle
      in groups III to V and in the tendons of the ventral oblique muscle in groups IV
      and V. There was a significant increase in the breadth of the dorsal straight and
      ventral oblique muscle tendons in groups IV and V and the tendons of the
      pyramidal muscle in groups III and V. The distance of the distal insertion of the
      tendon at the corneal limbus increased steadily with age in all the examined
      groups. The number of fascicles and muscle fibres, their diameter and length in
      all the studied EOMs were different in the different groups.

PMID- 29575918
TI  - Smallest lectin-like peptide identified from the skin secretion of an endemic
      frog, Hydrophylax bahuvistara.
AB  - Lectins are sugar-binding proteins and considered as attractive candidates for
      drug delivery and targeting. Here, we report the identification of the smallest
      lectin-like peptide (odorranalectin HYba) from the skin secretion of Hydrophylax
      bahuvistara which is being the shortest lectin-like peptide identified so far
      from the frog skin secretion, with 15 amino acid residues. The peptide is the
      first report from an Indian frog and lacks antimicrobial activity but strongly
      agglutinate intact human erythrocytes. The sequences at the L-fucose recognizing
      region is conserved as in other lectins reported from frog skin secretion and
      could be exploited for specificity and drug targeting properties.

PMID- 29575919
TI  - Effect of silver nanoparticles on phenolic compounds production and biological
      activities in hairy root cultures of Cucumis anguria.
AB  - The present study describes the elicitor effect of silver ion (Ag+) and
      biologically synthesized silver nanoparticles (AgNPs) to enhance the biomass
      accumulation and phenolic compound production as well as biological activities
      (antioxidant, antimicrobial and anticancer) in genetically transformed root
      (hairy root) cultures of Cucumis anguria. The biomass of hairy root cultures was
      significantly increased by AgNPs whereas decreased in Ag+ elicitation at 1 and 2
      mg/L. AgNPs-elicited hairy roots produced a significantly higher amount of
      individual phenolic compounds (flavonols, hydroxycinnamic and hydroxybenzoic
      acids), total phenolic and flavonoid contents than Ag+-elicited hairy roots.
      Moreover, antioxidant, antimicrobial and anticancer activities were significantly
      higher following AgNPs-elicitation compared with that in Ag+-elicited hairy
      roots. We suggest that AgNPs could be an efficient elicitor in hairy root
      cultures to increase the phytochemical production.

PMID- 29575921
TI  - TK1 overexpression is associated with the poor outcomes of lung cancer patients:
      a systematic review and meta-analysis.
AB  - AIM: The study aimed to unveil the effect of TK1 expression on the
      clinicopathological significance and prognosis in patients with lung cancer.
      Results & methodology: Studies for meta-analysis were selected according to a
      thorough literature search in databases (PubMed, EMBASE and Chinese databases).
      Ten studies containing 1393 lung cancer patients were investigated in our
      analysis. The TK1 overexpression was associated with poorer overall survival(OS)
      in lung cancer patients (hazard ratio = 1.881; 95% CI:1.318-2.684, Z = 3.48; p =
      0.001). Furthermore, The TK1 expression is associated with the
      clinicopathological features of lung cancer patients (tumor type, age, lymph node
      metastasis, distant metastasis and tumor, node, metastasis [TNM] stages). 
      Discussion & conclusion: The TK1 expression might have a supportive implication
      in assessing biological behavior and prognosis of lung cancer patients.

PMID- 29575922
TI  - Evaluation of the Area of the Lisfranc Ligament Damaged by Screw Fixation.
AB  - BACKGROUND: A cannulated screw is currently the standard fixation method to
      reduce and stabilize diastasis at the lisfranc joint following injury. Currently,
      there is no literature examining the area of the lisfranc ligament damaged by
      screw placement. The objective of this investigation is to define the area of the
      ligament damaged by fixation with a 3.5-mm cannulated screw. MATERIALS AND
      METHODS: Twelve cadaveric feet were dissected to identify the Lisfranc ligament
      metatarsal insertion site and origin on the medial cuneiform. A 3.5-mm cannulated
      screw was then passed over the course of the ligament and removed. The Lisfranc
      joint was then dissected to measure the dimensions of the ligament and damage
      from screw passage at the origin and insertion using imaging software. RESULTS:
      Mean injury area on the metatarsal was 3.49 mm2 and the area of injury for the
      cuneiform was 3.33 mm2. The mean percent of the area damaged was calculated to be
      1.75% and 2.43% at the cuneiform and metatarsal, respectively. CONCLUSION: A
      proportionally small area of the Lisfranc ligament is disrupted following screw
      fixation, but the implications of this on ligament healing and outcomes remain to
      be elucidated. LEVELS OF EVIDENCE: Level V: Cadaveric study.

PMID- 29575923
TI  - Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano
      scaffold for the repair of cartilage defect.
AB  - Cartilage defect is common in clinical but notoriously difficult to treat for low
      regenerative and migratory capacity of chondrocytes. Biodegradable tissue
      engineering nano-scaffold with a lot of advantages has been the direction of
      material to repair cartilage defect in recent years. The objective of our study
      is to establish a biodegradable drug-loading synthetic polymer (PLA) and
      biopolymer (Gelatine) composite 3D nano-scaffold to support the treatment of
      cartilage defect. We designed a microfluidic chip-based drug-screening device to
      select the optimum concentration of resveratrol, which has strong protective
      capability for chondrocyte. Then biodegradable resveratrol-loading PLA/Gelatine
      3D nano-scaffolds were fabricated and used to repair the cartilage defects. As a
      result, we successfully cultured primary chondrocytes and screened the
      appropriate concentrations of resveratrol by the microfluidic device. We also
      smoothly obtained superior biodegradable resveratrol-loading PLA/Gelatine 3D nano
      scaffolds and compared the properties and therapeutic effects of cartilage defect
      in rats. In summary, our microfluidic device is a simple but efficient platform
      for drug screening and resveratrol-loading PLA/Gelatine 3D nano-scaffolds could
      greatly promote the cartilage formation. It would be possible for materials and
      medical researchers to explore individualized pharmacotherapy and drug-loading
      synthetic polymer and biopolymer composite tissue engineering scaffolds for the
      repair of cartilage defect in future.

PMID- 29575924
TI  - What Can We Learn From Point-of-Care Blood Glucose Values Deleted and Repeated by
      Nurses?
AB  - BACKGROUND: Hospitals rely on point-of-care (POC) blood glucose (BG) values to
      guide important decisions related to insulin administration and glycemic control.
      Evaluation of POC BG in hospitalized patients is associated with measurement and
      operator errors. Based on a previous quality improvement (QI) project we
      introduced an option for operators to delete and repeat POC BG values suspected
      as erroneous. The current project evaluated our experience with deleted POC BG
      values over a 2-year period. METHOD: A retrospective QI project included all
      patients hospitalized at two regional academic medical centers in the Pacific
      Northwest during 2014 and 2015. Laboratory Medicine POC BG data were reviewed to
      evaluate all inpatient episodes of deleted and repeated POC BG. RESULTS:
      Inpatient operators choose to delete and repeat only 0.8% of all POC BG tests.
      Hypoglycemic and extreme hyperglycemic BG values are more likely to be deleted
      and repeated. Of initial values <40 mg/dL, 58% of deleted values (18% of all
      values) are errors. Of values >400 mg/dL, 40% of deleted values (5% of all
      values) are errors. Not all repeated POC BG values are first deleted. Optimal use
      of the option to delete and repeat POC BG values <40 mg/dL could decrease
      reported rates of severe hypoglycemia by as much as 40%. CONCLUSIONS: This
      project demonstrates that operators are frequently able to identify POC BG values
      that are measurement/operator errors. Eliminating these errors significantly
      reduces documented rates of severe hypoglycemia and hyperglycemia, and has the
      potential to improve patient safety.

PMID- 29575925
TI  - Standards for Medical Device Cybersecurity in 2018.

PMID- 29575926
TI  - Device and Method for Noninvasive Glucose Assessment.
AB  - BACKGROUND:: Intensive monitoring of blood glucose levels is crucial in diabetes
      management. This article presents a new device, the TensorTip Combo Glucometer
      (CoG), developed by Cnoga Medical Ltd, which enables to predict capillary tissue
      glucose concentration noninvasively. METHODS:: Noninvasive glucose readings
      usually provide irregular or disordered mathematical manifold over the
      measurement space. To establish a transfer function, which correctly correlates
      the noninvasive raw data and the actual invasive glucose level, we suggest a
      mathematical concept that employs a personal calibration procedure to associate
      glucose pattern and multiple optical signals derived from tissue response to
      light emission in the range of visible to IR. The traversed light is detected by
      a color image sensor to predict the tissue glucose concentration at the
      fingertip. This article presents the mathematical concept underlying the
      technology and the requirements for device operation. RESULTS:: The device was
      clinically evaluated and compared to standard invasive blood glucose monitoring
      devices in few medical centers and by home users. Based on consensus error grid
      analysis, more than 98% of the measurements of each study were in zones A (more
      than 81%) and B (more than 11%). Postmarketing evaluations showed high
      correlations comparing the CoG to other invasive reference devices. CONCLUSIONS::
      The CoG device employs a unique mathematical approach to predict glucose
      concentrations based on multiple optical signals. The first clinical results
      indicate that the device may show appropriate agreement with reference methods to
      be used for pain-free glucose assessment in daily routine.

PMID- 29575927
TI  - On-treatment platelet reactivity in peripheral and coronary blood in patients
      undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI).
AB  - Dual antiplatelet therapy is recommended in patients undergoing primary
      percutaneous coronary intervention (p-PCI) for ST-segment elevation myocardial
      infarction (STEMI). Pre-analytical variables may influence platelet function
      analysis results. Our aim was to evaluate the on-treatment platelet reactivity in
      peripheral artery vs coronary blood in patients with STEMI. We enrolled one
      hundred and nine patients who consecutively underwent p-PCI at Cardiology Unit of
      Padua University Hospital between June 2014 and June 2015. Before the procedure,
      all patients received intravenous aspirin 250 mg and either of the
      thienopyridines; clopidogrel 600 mg, prasugrel 60 mg or ticagrelor 180 mg. ASPI
      test and ADP-test using multiple electrode aggregometry (MEA) were performed in
      samples collected from both a peripheral artery and the culprit coronary artery.
      'Low responders' were patients with an ASPI-test or ADP-test value greater than
      or equal to a pre-established normal range. No significant differences were
      observed in ASPI-test values between peripheral (19 (median) [3-49 (10-90
      percentiles)] U) vs coronary (12 [1-40] U, p = .06) blood and in ADP-test (40 [14
      82] U vs 33 [7-79] U, p =.68) blood. In peripheral blood, fifteen (14%) patients
      were 'low aspirin' and forty-one (38%) 'low thienopyridines' responders. The
      prevalence of 'low clopidogrel' responders was higher (45%) than prasugrel (36%)
      and ticagrelor (33%). Similar results were observed in coronary blood. In
      patients undergoing p-PCI for STEMI, MEA platelet function observed in coronary
      arteries was consistent with peripheral artery blood's independently of the
      antiplatelet drug used. The clinical significance of peripheral and coronary on
      aspirin/thienopyridines platelet reactivity needs further clarification.

PMID- 29575928
TI  - Health-Related Quality of Life and Psychological Aspects of Adults With
      Hemophilia in Iran.
AB  - Hemophilia causes bleeding that may affect patients' psychological aspects and
      quality of life. This study aims to evaluate the impact of psychological aspects
      and pain on health-related quality of life (HRQoL) in adult patients with
      hemophilia. This cross-sectional study was conducted on 103 patients with
      hemophilia. Data were collected using hemophilia-specific quality of life,
      Depression Anxiety Stress Scales, and pain visual analogue scales. Data were
      analyzed using correlation coefficients, analysis of covariance, and regression
      analysis. The results showed that 71.7% of patients with hemophilia experienced
      pain on the study day. The mean score of HRQoL of patients with hemophilia was
      51.09 (standard deviation = 19.37). Moreover, 57.4%, 64.6%, and 44.6% of the
      patients had mild to severe depression, anxiety, and stress, respectively. In
      addition, a significant association was observed between HRQoL and depression,
      anxiety, and severity of pain. In the regression model, 48% of changes in HRQOL
      were explained by the study variables, with the severity of pain and depression
      being significant predictors. Therefore, attention should be paid to these
      aspects to improve patients' quality of life and psychosocial health.

PMID- 29575929
TI  - Short-term effect of kinesiology taping on temperature distribution at the site
      of application.
AB  - The aim of the study was to assess skin temperature after short-term kinesiology
      tape application. Seventy-four healthy volunteers with no history of lower back
      pain participated in the study. Kinesiology tape was applied in the experimental
      group, and Matopat Classic adhesive tape was applied in the placebo group. Study
      participants wore the tape for four consecutive days and were then
      thermographically analyzed for changes in skin temperature. Examination of skin
      surface temperature distribution revealed a significantly lower temperature (mean
      decrease, 1.3 degrees C P = .001 area1, 1.5 degrees C P = .001 area2, 1.6 P =
      .008 area3) immediately after kinesiology tape the removal. One hour after
      removal of the tape, a statistically significant increase in temperature was
      observed over all three areas (mean increase, 0.9 degrees C P = .025 area1, 1.0
      degrees C P = .0008 area2, 1.0 P = .011 area3). In group 2, there were no
      statistically significant temperature changes. Based on the findings, we
      determined that kinesiology taping may affect skin temperature at the site of
      application.

PMID- 29575930
TI  - In response to: fewer adverse effects with a modified two-bag acetylcysteine
      protocol in paracetamol overdose.

PMID- 29575931
TI  - Development of novel biotinylated chitosan-decorated docetaxel-loaded
      nanocochleates for breast cancer targeting.
AB  - The motive of study was to develop biotinylated chitosan (BI-CHI) decorated
      docetaxel (DTX) loaded nanocochleates (BI-CHI-DTX-NC) to achieve controlled drug
      release, improve bioavailability, targeted delivery and enhanced anticancer
      potency with the reduced systemic toxicity of DTX. The development involved the
      loading of DTX to nanocochleates (DTX-NC) through conversion of
      dimyristoylphosphatidylglycerol-sodium (DMPG-Na) and cholesterol bearing liposome
      on addition of calcium ions, followed by encapsulated DTX-NC with BI-CHI (BI-CHI
      DTX- NC) and compared with DTX and DTX-NC. The release of DTX indicated strong pH
      dependence and implies strong hydrogen-bonding between nanocochleates and DTX.
      Formulated BI-CHI-DTX-NC demonstrated higher in-vitro anticancer activity in
      biotin over expressed human breast cancer MCF-7 cells. The targeting effect for
      the BI-CHI-DTX-NC was also demonstrated. The concentration of the drug needed for
      growth inhibition of 50% of cells in a designed time period (GI50) was 1.8 MUg/ml
      for free DTX while it was decreased by 33.34% for the DTX-NC (1.2 MUg/ml).
      Furthermore, the GI50 value of BI-CHI-DTX-NC was 0.2 MUg/ml, i.e. an 88.89%
      decrease was observed as compared to DTX solution. Moreover, bioavailability of
      DTX from BI-CHI-DTX-NC was increased by 10-folds with longer circulation time and
      slower plasma elimination with low tissue distribution as compared to DTX
      solution. The results indicate that the BI-CHI-DTX- NC has the potential to be
      applied for targeting anticancer drug delivery.

PMID- 29575932
TI  - ECM based injectable thermo-sensitive hydrogel on the recovery of injured
      cartilage induced by osteoarthritis.
AB  - Intra-articular injection of anti-inflammatory drugs can be a promising strategy
      for recovery of injured articular cartilage. We prepared a series of injectable
      thermo-sensitive composite hydrogels, composed of Pluronic F127,
      glycosaminoglycan (GAG) and bone morphogenetic protein (BMP-2), which was
      designed to mimic extracellular matrix (ECM). The rheological properties and
      dissolution rate of composite hydrogels containing chondroitin sulfate or with
      different hyaluronic acid molecular mass (10k, 90k, 800k) were investigated.
      Meanwhile, bovine serum albumin (BSA) or FITC-BSA was chosen as model drug loaded
      into PF/GAG hydrogels to study their sustained release behavior in vitro. The
      results showed that hydrogels could maintain shapes for more than 16 days and the
      release rate of BSA in PF/GAG composite gels was much slower than in PF127 gels,
      due to the affinity between BSA and GAG. Furthermore, increasing the molecular
      weight of hyaluronic acid correspondingly increased hydrogel dissolution rate and
      BSA release in the hydrogels. Subsequently, MTT experiments were performed to
      investigate the toxicity of the hydrogels on mouse pre-osteoblast cell MC3T3-E1.
      In vivo anti-inflammation results showed that PF/GAG@BMP-2 composite hydrogels
      had the most efficient efficacy on recovery of injured cartilage, which is
      induced by osteoarthritis, compared to the control groups (PF127@BMP-2 or BMP-2
      saline solution).

PMID- 29575933
TI  - Comparison of the everolimus concentrations measured in whole blood with
      everolimus QMS or sirolimus CMIA.
AB  - Few years ago, it was proposed that everolimus blood levels could be determined
      with the commercially available sirolimus chemiluminescence magnetic
      microparticle immunoassay (CMIA). More recently, a highly specific microsphere
      system (QMS) has been approved by FDA for therapeutic drug monitoring in humans.
      Aim of the present study was to compare the results of everolimus assay performed
      with everolimus QMS and with sirolimus CMIA. The two methods were compared with
      Passing-Bablok regression and Bland-Altman plot analysis. The Passing-Bablok
      regression analysis showed that although the results obtained with the two
      techniques were significantly correlated, CMIA-measured differed from QMS
      measured everolimus concentrations by both a systematic and a proportional error.
      Specifically, at blood levels lower than 5 ng/mL CMIA were lower than QMS
      measured everolimus concentrations. On the opposite, at everolimus blood
      concentrations higher than 10 ng/mL CMIA-estimated values became progressively
      higher than QMS-measured everolimus concentrations. The analysis of the Bland
      Altman plot showed a less than optimal agreement of the two tests (5.59% of the
      data point outside the +/-1.96 SD interval). Moreover, the relationship between
      the difference between EveroQMS and EveroCMIA and their average was clearly
      concentration dependent with positive and negative values at concentration values
      lower and higher than 5 ng/mL respectively. In conclusion, our finding showed
      that the values of everolimus concentrations measured with sirolimus CMIA differ
      from those detected with the FDA-approved everolimus QMS further suggesting that
      sirolimus CMIA should not be used anymore for everolimus therapeutic drug
      monitoring.

PMID- 29575934
TI  - Work-family spillover and metabolic syndrome indicators: Findings from a national
      sample.
AB  - This study examines the link between negative work-family spillover and metabolic
      risk factors over a 9-year period. Data from two waves of the Midlife in the
      United States Survey were used to explore relationships between negative work
      family spillover and four indicators of metabolic syndrome-blood pressure,
      triglycerides, body mass index, and glucose levels. In a sample of full-time
      working men and women ( N = 630), increased negative spillover at baseline
      significantly predicted higher body mass index nearly a decade later, with a
      marginally significant effect for triglyceride levels. Increases in spillover
      also body mass index and glucose levels at follow-up. This study extends research
      tying work-life spillover to health and suggests that further investigation is
      needed to fully understand the long-term effects of work stress.

PMID- 29575935
TI  - Pathways linking family stress to youth delinquency and substance use: Exploring
      the mediating roles of self-efficacy and future orientation.
AB  - African American adolescents in poorer neighborhoods experience significant
      sanctions related to drug use and delinquency. Parental stress (i.e. substance
      use, mental distress, and incarceration) is associated with youth drug use and
      delinquency. We examined whether high self-esteem and positive future orientation
      mediated parental stress and youth substance use and delinquency. Demographic,
      family stress, future orientation, self-esteem, and drug use data were collected
      from 578 youths. Major findings indicated that self-esteem mediated the
      relationship between family stress and both drug use and delinquency. Future
      mediated the relationship between family stress and delinquency. Resiliency
      factors may promote positive development for low-income youth.

PMID- 29575936
TI  - Bilateral simultaneous primary choroidal melanomas: Treated with palladium-103
      plaque radiation.
AB  - PURPOSE: To provide a clinical description of a case of bilateral choroidal
      melanoma in a patient treated with palladium-103 (103Pd) plaque brachytherapy.
      METHODS: An 81-year-old man presented with choroidal melanoma in both eyes. In
      consideration of tumor sizes and locations, treatment involved insertion of 103Pd
      radioactive plaque in the right eye followed by the left at an interval of 2
      months. RESULTS: At 1-year follow-up, bilateral local control has been associated
      with apical tumor height regression, and visual acuity has been preserved (20/20
      in the right eye and 20/25 in the left). Exudative subretinal fluid has resolved.
      There has been no metastasis. CONCLUSION: Bilateral choroidal melanomas are rare,
      reported to be either simultaneous or sequential as well as treatable. In this
      case, we were able to achieve tumor regression and preserve visual acuity in both
      eyes after plaque brachytherapy.

PMID- 29575937
TI  - BP1, a potential biomarker for breast cancer prognosis.
AB  - Homeobox genes are critical in tumor development. An isoform protein of DLX4
      called BP1 is expressed in 80% of invasive ductal breast carcinomas. BP1
      overexpression is implicated in an aggressive phenotype and poor prognosis. BP1
      upregulation is associated with estrogen receptor negativity so those tumors do
      not respond to antiestrogens. Breast cancer is the second leading cause of death
      in women. BP1 could serve as both a novel prognostic biomarker for breast cancer
      and a therapeutic target. In this review, we address the role of BP1 protein in
      tumorigenesis of breast cancer and four other malignancies. A number of functions
      of BP1 in cancer are also discussed.

PMID- 29575938
TI  - Factors associated with post-treatment E. coli contamination in households
      practising water treatment: a study of rural Cambodia.
AB  - The purpose of this study was to assess factors associated with Escherichia coli
      (E. coli) contamination in rural households in Cambodia that have adopted
      household water treatment. The following factors were significantly associated
      (alpha < 0.05) with apparent E. coli contamination: cleaning the drinking vessel
      with untreated water, not drying the cup (with a cloth), accessing treated water
      by the use of a scoop (ref: using a tap), having more than one untreated water
      storage container, having an untreated water storage container that appeared
      dirty on the outside, and cows living within 10 m of the household. This study
      provides further evidence confirming previous studies reporting an association
      between inadequate cleanliness of water storage containers and household drinking
      water contamination, and identifies practical recommendations statistically
      associated with reduced post-treatment E. coli contamination in the household
      setting in rural Cambodia.

PMID- 29575939
TI  - Mechanism of MALAT1 preventing apoptosis of vascular endothelial cells induced by
      oxygen-glucose deficiency and reoxidation.
AB  - BACKGROUND: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular
      dysfunction characterized by endothelial cell injury or death. Metastasis
      associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be
      associated with endothelial dysfunction. Our study aimed to investigate the
      effect of MALAT1 on vascular endothelium. METHODS: In this study, oxygen-glucose
      deprivation and reoxygenation (OGD-R) were used as in vitro studies to
      investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular
      endothelial cells in an I/R injury model. Primary human brain microvascular
      endothelial cells were cultured on the condition of OGD-R and MALAT1 expression
      levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation.
      The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed
      the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and
      the change of Akt signal was detected by Western-blot. RESULTS: After OGD-R, over
      expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K)
      activity and activation of Akt phosphorylation, while decreased apoptosis and
      caspase 3 activity. Moreover, these effects could be successfully eliminated by
      treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1
      lentivirus reduced PI3K activity and Akt phosphorylation, while increased
      apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no
      significant effect on that OGD-R-induced reactive oxygen species (ROS)
      production. CONCLUSIONS: This study first proposed that lncRNA MALAT1 can protect
      human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a
      PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential
      new therapeutic target for brain I/R injury.

PMID- 29575940
TI  - A Tablet-Based Educational Tool: Toward More Comprehensive Pediatric Patient
      Education.
AB  - There is a paucity of data on the impact of mobile technology on physician-led
      education in the pediatric population. We performed a prospective pilot study in
      a pediatric diabetes clinic to evaluate the impact of tablet-based patient
      education. A total of 106 patients and caregivers completed postclinic surveys,
      64 (60%) in the intervention group and 42 (40%) in the control group. The
      majority of the intervention group patients (86%) liked tablet use and felt it
      was better or similar (99%) to baseline. Moreover, a majority receiving tablet
      based education perceived an increase in diabetes knowledge (57%) compared with
      baseline (39%), though the difference did not reach statistical significance ( P
      = .059). Those who received tablet-based education felt they were educated on
      more diabetes-related topics. As the use of mobile technology in medicine grows,
      additional research is needed to compare mobile technology with traditional
      methods in providing education to the pediatric population.

PMID- 29575941
TI  - Treatment outcomes of conventional or high-dose ranibizumab for vascularized
      pigment epithelial detachment based on lesion subtypes.
AB  - INTRODUCTION:: A post hoc study was conducted to compare visual and anatomic
      outcomes of vascularized serous pigment epithelial detachment (Group 1) with
      fibrovascular pigment epithelial detachment (Group 2) due to age-related macular
      degeneration treated with either 0.5 or 2.0 mg ranibizumab injections. METHODS::
      A prospective, randomized trial was performed with the following regimens for 12
      months: (1) 0.5 mg monthly, (2) 0.5 mg monthly for 4 months followed by pro re
      nata injections, (3) 2.0 mg monthly, and (4) 2.0 mg monthly for 4 months followed
      by pro re nata injections. Primary measure was best-corrected standardized
      vision. Secondary measures included central subfield, thickness surface area A2,
      greatest linear diameter, heights of pigment epithelial detachment and choroidal
      neovascularization (CNV), subretinal fluid, cystoid macular edema, and adverse
      events. RESULTS:: For 36 eyes (8 in Group 1 and 28 in Group 2), follow-up time
      was 12 months. There were no differences in baseline features between groups
      except for pigment epithelial detachment A2 (Group 2 > Group 1). Two-way analysis
      of variance showed comparable improvements in anatomic and vision outcomes. Three
      way analysis of variance also showed similar responses for both lesion subtypes
      with high-dose treatment. There was a trend toward greater pigment epithelial
      detachment resolution in Group 1 eyes. There were no differences in
      retinochoroidal angiomatous proliferation (Type-3 CNV) and cataracts between
      groups, although greater percentages of eyes in Group 1 developed retinal pigment
      epithelial tears (25% vs 10.7%). CONCLUSION:: There were no differences in vision
      and anatomic outcomes between lesion subtypes, and similarly, more rapid
      responses to high-dose than conventional-dose ranibizumab occurred for eyes with
      both lesion subtypes. More retinal pigment epithelial tears may develop in eyes
      with vascularized serous pigment epithelial detachment.

PMID- 29575942
TI  - Effects of Plantago lanceolata L. extract on full-thickness excisional wound
      healing in a mouse model.
AB  - Wound healing requires cells that increase both collagen production as a result
      of inflammatory events and regeneration of epithelial tissue. The Plantago
      species of herbs have been used in traditional treatment of skin disorders and
      infectious diseases, and digestive, respiratory, reproductive and circulatory
      conditions. We investigated the efficacy of different concentrations of Plantago
      lanceolata L. extract (PLE) for wound healing owing to its anti-inflammatory,
      anti-bacterial, anti-fungal, anti-oxidant, anti-ulcerative, analgesic and
      immunomodulatory properties. We used 72 mice in four groups of 18. An excisional
      1 cm wound was created in the skin on the back of the mice in all groups. An
      ointment containing 10% PLE was applied to the wound in group 1, an ointment
      containing 20% PLE was applied in group 2 and vaseline was applied in group 3. In
      group 4, no treatment was applied to the wound. On days 7, 14, and 21 of the
      experiment, six animals in each group were sacrificed after the wounds were
      photographed and specimens from the wound sites were examined. On day 14,
      epithelialization was more prominent in group 2, while vascularization and
      collagen deposition was more advanced in groups 1 and 2 compared to the other
      groups. Immunohistochemical examination revealed that TGF-beta1 expression was
      elevated on day 14 in all groups; however, this elevation was more limited in
      groups 1 and 2 than in groups 3 and 4. Although ANGPT-2 expression increased in
      groups 1 and 4 on day 14, it decreased significantly in groups 2 and 3. We found
      that different concentrations of PLE exhibited positive effects on wound healing.
      Application of 10% PLE ointment may be a useful strategy for wound healing.

PMID- 29575943
TI  - Prevalence of prenatal and postpartum depression and associated factors among HIV
      infected women in public primary care in rural South Africa: a longitudinal
      study.
AB  - This study aimed to assess the longitudinal prevalence of prenatal and postnatal
      depression and associated factors among HIV-infected women in rural South Africa.
      In a longitudinal, cluster-randomized, prevention of mother to child transmission
      (PMTCT) intervention trial, 681 HIV-infected prenatal women in 12 community
      health centres in Mpumalanga province, South Africa, were recruited in 2015 by
      consecutive sampling at 8-24 weeks pregnancy and followed up at 32 weeks
      prenatally, and 6 and 12 months postpartum (retention rate = 59.2%). Results
      indicate that at baseline, 48.7% of the women screened positive for depression
      (scores of >=13 on the "Edinburgh Postnatal Depression Scale 10"), while
      postnatally (at 12 months) the prevalence was 35.6%. Mothers who did not have
      depression before or after were 205 (50.1%), those who had depression before and
      after were 58 (14.4%), those who had depression only before were 81 (20.1%), and
      those who had depression only after were 59 (14.6%). In multinominal logistic
      regression analyses, less education and physical and psychological intimate
      partner violence were associated with sustained perinatal depression.
      Participation in the PMTCT intervention was associated with remitting depression
      while alcohol use was associated with the onset of postnatal depression. Using
      generalized linear mixed models in longitudinal analyses, psychological partner
      violence, lack of male involvement during pregnancy and non-adherence to
      antiretroviral treatment were associated with depression. In conclusion, a high
      pre- and postnatal prevalence of depression was found highlighting the utility of
      interventions to address prevention and treatment of perinatal depression.

PMID- 29575944
TI  - The diagnosis and management of extramammary Paget's disease.
AB  - INTRODUCTION: Extramammary Paget's disease (EMPD) is a rare neoplastic condition
      that commonly affects the anogenital area in the elderly. Owing to its low
      incidence, limited data regarding EMPD's diagnosis and treatment have been
      available. This review article aims to explore the current knowledge of EMPD to
      improve the management of this disease. Areas covered: This review outlines the
      diagnosis and management of EMPD. Articles on this issue that had been published
      in PubMed were identified and surveyed. We provide an overview of the reported
      studies, focusing on the recent advances in this field. Expert commentary: A new
      TNM staging system specific for EMPD has been proposed in Japan; the T category
      was classified by tumor thickness and lymphovascular invasion, the N category by
      the number of metastatic lymph nodes, and the M category by systemic metastases.
      As new diagnostic tools for EMPD, dermoscopy and reflectance confocal microscopy
      have emerged. Recent reports about Mohs micrographic surgery, mapping biopsy,
      radiation therapy, photodynamic therapy, topical imiquimod, conventional
      chemotherapy, and targeted therapy are also discussed. Despite the increasing
      publications of EMPD, limited information on this condition is available and the
      accumulation of more data is required.

PMID- 29575945
TI  - Current approaches to challenging scenarios in myeloproliferative neoplasms.
AB  - INTRODUCTION: The Philadelphia chromosome-negative myeloproliferative neoplasms
      (MPNs) including polycythemia vera, essential thrombocythemia and primary
      myelofibrosis are clonal hematological malignancies that originate at the level
      of the hematopoietic stem cell, and are characterized by excessive proliferation
      of cells belonging to one or more of the myeloid lineages. Central to the
      pathogenesis of the MPNs is constitutive activation of the JAK/STAT signaling
      pathway due to a family of driver mutations affecting JAK2, CALR or MPL. These
      disorders share common clinical and laboratory features, a significant burden of
      systemic symptoms, increased risk of developing arterial and venous thrombotic
      events, and the potential to progress to myelofibrosis and acute leukemia. Areas
      covered: We identified four clinical situations which represent challenging
      management dilemmas for patients with MPNs. Our conclusions and recommendations
      are based on a literature search using MEDLINE and recent meeting abstracts using
      the keywords, focusing on publications directly addressing these scenarios and on
      recent contributions to the field. Expert commentary: Multi-center efforts to
      study large cohorts of MPN patients have led to more uniform and evidence-based
      approaches to key aspects in MPN management. However, treatment strategies to
      deal with specific clinical scenarios are lacking.

PMID- 29575946
TI  - The use of immunotherapy for the treatment of tuberculosis.
AB  - INTRODUCTION: Tuberculosis (TB) is the first cause of mortality by a single
      infectious agent in the world, causing more than one million deaths worldwide as
      reported by the World Health Organization (WHO). For the optimal control of TB
      infection, a protective immune response that limits bacterial spread without
      causing damage to the host is essential. Although most healthy individuals are
      capable of generating protective responses, patients who suffer pulmonary TB
      commonly present a defective immune function. Areas covered: We intend to
      highlight the potential of novel immunotherapeutic strategies that enhance and
      promote effective immune responses. The following methodology was undertaken for
      establishing a literature search: the authors used PubMed to search for
      'Pulmonary Tuberculosis' and keywords that denoted the novel immunotherapeutic
      strategies discussed in length in the text including antibodies, antimicrobial
      peptides, cell therapy, cytokines and gene therapy. Expert commentary: The
      current therapeutic regimens for this disease are complex and involve the
      prolonged use of multiple antibiotics with diverse side effects that lead to
      therapeutic failure and bacterial resistance. The standard appliance of
      immunotherapy and its deployment to vulnerable populations will require
      coordinated work and may serve as a powerful tool to combat the ensuing threat of
      TB.

PMID- 29575947
TI  - The utility of 25-question Geriatric Locomotive Function Scale for evaluating
      functional ability and disease activity in Japanese rheumatoid arthritis
      patients: A cross-sectional study using NinJa database.
AB  - OBJECTIVES: To investigate the distribution of 25-question Geriatric Locomotive
      Function Scale (GLFS-25) scores in Japanese rheumatoid arthritis (RA) patients
      and evaluate relationships with clinical variables. METHODS: Among 15,115
      patients registered in the NinJa database for fiscal year 2015, 1710 with
      complete GLFS-25 and disease activity score-28 (DAS28) data were analyzed.
      Correlations between GLFS-25 score and clinical variables were assessed by
      Spearman coefficients. Mean GLFS-25 scores were compared among DAS28 groups
      (<2.6, 2.6-3.1, 3.2-5.0, >=5.1) using the Kruskal-Wallis test. To evaluate the
      performance of the GLFS-25 and Health Assessment Questionnaire Disability Index
      (HAQ-DI) for predicting DAS28 >= 3.2 (moderate/high disease activity), receiver
      operator characteristic (ROC) curves were constructed. RESULTS: GLFS-25 score was
      significantly correlated with age, disease duration, DAS28, and HAQ-DI. GLFS-25
      score increased in parallel with DAS28. The proportion of patients with
      locomotive syndrome stage 2 also increased with DAS28. Area under the curve
      values for HAQ-DI and GLFS-25 score were 0.739 and 0.768, respectively. At a GLFS
      25 positive cutoff score >=16, sensitivity was 0.716 and specificity was 0.661
      for predicting DAS28 >= 3.2. CONCLUSION: This study documents the GLFS-25 score
      distribution in Japanese RA patients and demonstrates that GLFS-25 is a useful
      measure for evaluating functional ability in RA.

PMID- 29575948
TI  - Blood biomarkers in chronic airways diseases and their role in diagnosis and
      management.
AB  - INTRODUCTION: The complexity and heterogeneous nature of asthma and chronic
      obstructive pulmonary disease (COPD) results in difficulties in diagnosing and
      treating patients. Biomarkers that can identify underlying mechanisms, identify
      patient phenotypes and to predict treatment response could be of great value for
      adequate treatment. Areas covered: Biomarkers play an important role for the
      development of novel targeted therapies in airways disease. Blood biomarkers are
      relatively non-invasive, easy to obtain and easy to apply in routine care.
      Several blood biomarkers are being used to diagnose and monitor chronic airways
      diseases, as well as to predict response to treatment and long-term prognosis.
      Blood eosinophils are the best studied biomarker, the most applied in clinical
      practice, and until now the most promising of all blood biomarkers. Other blood
      biomarkers, including serum periostin, IgE and ECP and plasma fibrinogen are less
      studied and less relevant in clinical practice. Recent developments include the
      use of antibody assays of many different cytokines at the same time, and 'omics'
      techniques and systems medicine. Expert commentary: With the exception of blood
      eosinophils, the use of blood biomarkers in asthma and COPD has been rather
      disappointing. Future research using new technologies like big-data analysis of
      blood samples from real-life patient cohorts will probably gain better insight
      into underlying mechanisms of different disease phenotypes. Identification of
      specific molecular pathways and associated biomarkers will then allow the
      development of new targets for precision medicine.

PMID- 29575949
TI  - Detailed Magnetic Resonance Imaging (MRI) Analysis in Infantile Spasms.
AB  - PURPOSE: To evaluate initial magnetic resonance imaging (MRI) abnormalities in
      infantile spasms, correlate them to clinical characteristics, and describe repeat
      imaging findings. METHODS: A retrospective review of infantile spasm patients was
      conducted, classifying abnormal MRI into developmental, acquired, and nonspecific
      subgroups. RESULTS: MRIs were abnormal in 52 of 71 infantile spasm patients (23
      developmental, 23 acquired, and 6 nonspecific) with no correlation to the
      clinical infantile spasm characteristics. Both developmental and acquired
      subgroups exhibited cortical gray and/or white matter abnormalities. Additional
      abnormalities of deep gray structures, brain stem, callosum, and volume loss
      occurred in the structural acquired subgroup. Repeat MRI showed better definition
      of the extent of existing malformations. CONCLUSION: In structural infantile
      spasms, developmental/acquired subgroups showed differences in pattern of MRI
      abnormalities but did not correlate with clinical characteristics.

PMID- 29575950
TI  - Discourses of professionalism: Metaphors, theory and practice.
AB  - : Professionalism is a contested concept and different discourses have differed
      by scope and epistemology. The theory of communicative action integrates
      epistemology (knowledge interests) with that of scope (lifeworld). AIM: To
      pragmatically inform learning of professionalism. METHODS: apply the theory of
      communicative action to professionalism discourses. RESULTS: Previous
      professionalism discourses translated into four frames: technical; communicative;
      improvement, and critical. These can be viewed as four metaphors the scale;
      conversation; consensus conference, and protest. The theory of communicative
      action demonstrated that a critical frame was often lacking from discussions of
      professionalism and emphasized critiquing the assumptions made, the way power was
      utilized, and the ends to which actions were directed. Using these frameworks
      connected discourses on professionalism to other key medical discourses
      particularly quality improvement, patient centeredness, social justice, and the
      professional well-being. CONCLUSION: The theory of communicative action adds
      value by introducing criteria for the evaluation of individual truth claims that
      expands the discussion beyond accuracy to include sincerity, ethics and
      coherence; and it emphasizes promoting free speech and the inclusion of diverse
      views and stakeholders. The theory of communicative action provides a coherent
      and useful framework for viewing professionalism that integrates with broader
      discussions about philosophy, truth claims, and post-modern society.

PMID- 29575951
TI  - Concurrent training protocol for men with androgen deficiency in the aging male:
      a randomized clinical trial.
AB  - BACKGROUND: The androgen deficiency in the aging male (ADAM) affects physical,
      sexual, and psychological aspects with characteristics symptoms of middle-aged
      men. The practice of regular physical activity and physical exercise can
      attenuate these symptoms. The aim of this randomized clinical trial is to propose
      a physical exercise protocol based on concurrent training for middle-aged men
      with ADAM. METHOD: Randomized clinical trial with a 6-month intervention will
      randomly divided into two groups: experimental group (EG) and control group (CG).
      Four evaluations will be carried out, (1) pre-intervention; (2) in the first
      month of intervention; (3) in the third month of intervention; (4) post
      intervention, evaluating: physical, psychological, sexual, and hormonal aspects.
      The intervention protocol with concurrent training will have duration of 6
      months; frequency of 3 times weekly, with 60 min per session. The two-way ANOVA
      test will be used for the inter-group and intra-group comparisons with repeated
      measurements, and also Sydak's comparison test. CONCLUSION: This protocol was
      developed with the intent of easing the symptoms of ADAM. In addition, it is
      believed that the concurrent training protocol could be capable to recover
      hormonal, physical, psychological, and sexual aspect of middle-aged men with
      ADAM.

PMID- 29575952
TI  - Association between dietary flavonoids intake and obesity in a cohort of adults
      living in the Mediterranean area.
AB  - Dietary polyphenols, including flavonoids, are abundantly present in a healthy
      and balanced diet. Evidence for their role in preventing non-communicable
      diseases is emerging. We examined the association between estimated habitual
      intake of dietary flavonoid and obesity in a cohort study. After adjusting for
      potential confounding factors, inverse association between total flavonoid intake
      and excess weight (BMI >=25) was found (OR = 0.66, 95% CI: 0.45, 0.99); among
      individual classes of flavonoids, only flavanones were inversely associated with
      excess body weight (OR = 0.68, 95% CI: 0.48, 0.97). However, when considering
      adjustment for dietary factors (adherence to the Mediterranean diet), the
      associations were no more significant. When considering obesity as the outcome
      (BMI >=30), individuals with high intake of total flavonoids and flavonols
      resulted less likely to be obese (OR = 0.38, 95% CI: 0.21, 0.66 and OR = 0.63,
      95% CI: 0.39, 0.99, respectively), even after adjustment for confounding factors.
      The results of the present study add to the current literature further evidence
      of the association between higher flavonoid intake and decreased body weight.
      Further studies are needed to confirm retrieved association.

PMID- 29575954
TI  - Ototoxicity: The Radical Drum Beat and Rhythm of Cochlear Hair Cell Life and
      Death.
AB  - The function and structure of the auditory information processing system
      establishes a unique sensory environment for the "perfect storm." The battle
      between life and death pits the cascade of an apoptotic storm, programmed cell
      death cascades, against simple cell death (necrosis) pathways. Live or die, the
      free radical biology of oxygen and hydroxylation, and the destruction of
      transition metal migration through the mechanical gate sensory processes of the
      hair cell lead to direct access to the cytoplasm, cytoplasmic reticulum, and
      mitochondria of the inner workings of the hair cells. These lead to subsequent
      interactions with nuclear DNA resulting in permanent hearing loss. The yin and
      yang of pharmaceutical product development is to document what kills, why it
      kills, and how do we mitigate it. This review highlights the processes of cell
      death within the cochlea.

PMID- 29575953
TI  - Comparison of accepted and unaccepted living kidney donors: one-center
      experience.
AB  - BACKGROUND: Kidney transplantation from living donors (LD) has stagnated in many
      countries. This study aimed to check whether correction of LD selection practice
      could increase the number of kidney transplantations. METHODS: From January 2003
      to December 2012, 241 potential adult LD were evaluated in our hospital. Outcome
      (mortality and end-stage renal disease-ESRD) of accepted LD (182) was compared
      with unaccepted (59) donors. RESULTS: Mortality of LD was comparable with that
      for the standardized Serbian population (SMR = 1.104; 95% CI (0.730-1.606). Among
      evaluated potential LD, almost every fourth had been unaccepted, but reasons were
      modifiable in 42.4% of them. In pre-donation period unaccepted donors were
      significantly older, measured glomerular filtration rate was lower, with higher
      15-year and lifelong projected ESRD risks than accepted donors. Despite this, ten
      years outcome of both groups LD was similar: none of LD developed ESRD, 9.8% of
      accepted and 11.8% of unaccepted LD died (p = .803). CONCLUSIONS: During an
      average of 101 months of follow-up mortality of accepted LD did not differ
      significantly as compared to the age standardized Serbian population and none of
      them developed ESRD. In examination of potential LD, the use of accurate and
      precise methods for kidney function estimation and the evaluation of risk for
      ESRD and mortality as well as treatment of modifiable contraindications for
      kidney donation are necessary.

PMID- 29575955
TI  - Biofeedback in patients with ileoanal pouch dysfunction: a specialist centre
      experience.
AB  - OBJECTIVES: To report outcomes following biofeedback for functional problems
      associated with an ileoanal pouch. Incontinence and evacuatory disorders
      associated with the ileoanal pouch can be particularly problematic and difficult
      to treat using conventional therapies. Biofeedback therapy is a behavioural
      treatment that offers a non-surgical approach as an alternative or adjunct for
      patients. MATERIALS AND METHODS: This was a retrospective single centre study. We
      reviewed the notes of all patients attending for biofeedback at our institution
      between January 2012 and October 2017 and identified all those that did so for
      ileoanal pouch related problems. We recorded patient reported subjective
      improvements following biofeedback. The validated International Consultation on
      Incontinence Questionnaire was used to assess improvement in incontinent symptoms
      and the evacuatory disorder questionnaire was used to assess improvement in
      evacuatory disorders. RESULTS: Twenty-six patients with ileoanal pouch related
      problems underwent biofeedback. Based on patients' feedback at next clinical
      encounter following biofeedback, nine reported much improvement, 11 reported some
      improvement and six reported no improvement. In the group treated for
      incontinence, quality of life improved significantly from a median pre-treatment
      score of 80 to a post-treatment score of 41 (p = .01). Biofeedback reduced pain,
      bloating straining and laxative use in patients with evacuatory disorders.
      CONCLUSIONS: Biofeedback may be associated with significant improvement in
      quality of life as well as possible improvements in symptoms related to both
      incontinence and evacuatory disorders. It is probably an underused service.
      Further larger prospective studies are required to properly assess the efficacy
      of biofeedback in ileoanal pouch related dysfunction.

PMID- 29575956
TI  - Relation of locus 1p13 rs646776 polymorphism with the risk of preeclampsia.
AB  - OBJECTIVE: This study aimed to assess the relation of locus 1p13 rs646776 (T/C)
      polymorphism with preeclampsia in Egyptian women. METHODS: The study included 100
      healthy pregnant female subjects and 100 preeclampsia patients. The genotypes of
      the polymorphisms were assessed. Endothelin-1 level was determined in plasma.
      RESULTS: The major T allele of the 1p13.3 genomic region rs646776 polymorphism
      had a higher frequency in preeclampsia patients. Carriers of C allele had
      significantly lower endothelin-1 levels, lower systolic and diastolic blood
      pressure, decreased proteinuria, and increased HDL-C in the patients. CONCLUSION:
      The rare C allele of rs646776 polymorphism in chromosomal locus 1p13.3 is
      associated with decreased risk of preeclampsia.

PMID- 29575957
TI  - Ventilator-induced lung injury during controlled ventilation in patients with
      acute respiratory distress syndrome: less is probably better.
AB  - INTRODUCTION: Mechanical ventilation is required to support respiratory function
      in the acute respiratory distress syndrome (ARDS), but it may promote lung
      damage, a phenomenon known as ventilator-induced lung injury (VILI). Areas
      covered: Several mechanisms of VILI have been described, such as: inspiratory
      and/or expiratory stress inducing overdistension (volutrauma); interfaces between
      collapsed or edema-filled alveoli with surrounding open alveoli, acting as stress
      raisers; alveoli that repetitively open and close during tidal breathing
      (atelectrauma); and peripheral airway dynamics. In this review, we discuss: the
      definition and classification of ARDS; ventilatory parameters that act as VILI
      determinants (tidal volume, respiratory rate, positive end-expiratory pressure,
      peak, plateau, driving and transpulmonary pressures, energy, mechanical power,
      and intensity); and the roles of prone positioning and muscle paralysis. We seek
      to provide an up-to-date overview of the evidence in the field from a clinical
      perspective. Expert commentary: To prevent VILI, mechanical ventilation
      strategies should minimize inspiratory/expiratory stress, dynamic/static strain,
      energy, mechanical power, and intensity, as well as mitigate the hemodynamic
      consequences of positive-pressure ventilation. In patients with moderate to
      severe ARDS, prone positioning can reduce lung damage and improve survival.
      Overall, volutrauma seems to be more harmful than atelectrauma. Extracorporeal
      support should be considered in selected cases.

PMID- 29575958
TI  - Overall benefits provided by orthopedic surgical intervention in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To clarify systemic effects of orthopedic surgical intervention in
      patients with rheumatoid arthritis (RA). METHODS: A prospective observational
      cohort study was performed in RA patients who were scheduled to have primary
      elective orthopedic surgeries. Assessments were performed at baseline, 6 and 12
      months after surgery using J-HAQ, General Health, EQ-5D, BDI-II, DAS28-CRP(4) and
      CRP for all registered patients, DASH and grip power for patients with upper
      extremity surgeries, TUG for patients with lower-extremity surgeries, and JSSF
      for patients with ankle and forefoot surgeries. RESULTS: There were 294 sites in
      276 patients whose average age was 64 (19-89) years and average disease duration
      was 16 (1-60) years. Surgical site was shoulder in six patients, elbow in 26,
      wrist in 74, hand in 63, hip in 13, knee in 50, ankle in 12, and forefoot in 50.
      In total, physical function (J-HAQ, grip power, DASH, TUG, JSSF), quality of life
      (J-HAQ, General Health, EQ-5D) and depression (BDI-II) improved and disease
      activity (CRP, DAS28-CRP(4)) decreased significantly 6 and 12 months after
      surgery (p<.01), despite some differences in their outcomes by the preoperative
      disease activity and the surgical site. CONCLUSION: Overall benefits were
      provided by orthopedic surgical intervention generally in patients with RA.

PMID- 29575959
TI  - Pharmacological management of interstitial cystitis /bladder pain syndrome and
      the role cyclosporine and other immunomodulating drugs play.
AB  - INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a
      symptomatic disorder characterized by pelvic pain and urinary frequency.
      Immunological responses are considered as one of the possible etiologies of
      IC/BPS. In this review, we focused on emerging targets, especially on those
      modulating immunological mechanisms for the treatments of IC/BPS. Area covered:
      This review was based on the literature search of PubMed/MEDLINE, for which key
      words following bladder pain syndrome, interstitial cystitis, and/or cyclosporine
      A (CyA) were used. We discussed current treatments and the drugs targeting the
      immune responses including CyA and other drugs with different mechanisms
      including NGF antibodies and P2X3 antagonists. Expert commentary: IC/BPS is often
      difficult to treat by current treatments. Immunosuppression agents, especially
      CyA are considered as effective treatments for IC/BPS with Hunner's lesion
      because these drugs suppress the inflammatory responses in the bladder underlying
      urinary symptoms of the disease. Base on the previous literatures, we should use
      CyA for the refractory IC/BPS, especially that with Hunner's lesion due to its
      side effects. New drugs targeting other mechanisms such as urothelial or afferent
      nerve dysfunction or new delivery systems such as sustained drug releasing
      devices or gene therapy techniques may be promising for the future treatments of
      IC/BPS.

PMID- 29575961
TI  - Effect of magnetic field on haemodynamic perturbations in atherosclerotic
      coronary arteries.
AB  - Haemodynamic perturbations including elevated blood viscosity, low and
      oscillatory shear stress are understood to be important pathogenic mediators in
      atherosclerosis. These haemodynamic abnormalities are influenced by the presence
      of a magnetic field. This study conducted computational fluid dynamics (CFD)
      analysis in 4 coronary artery models, derived from authentic human coronaries,
      with mild and moderate and severe stenosis severity. The aim was to investigate
      the effect of a static magnetic field of varying intensities on blood viscosity,
      areas of low wall shear stress (ALWSS), maximum wall shear stress (MWSS) and
      length and volume of flow recirculation zones. The results showed that the
      magnetic field results in both beneficial and detrimental changes in
      haemodynamics. The beneficial effects are lowered viscosity, decreased size of
      ALWSS and flow recirculation zones whereas the detrimental effect is increased
      MWSS. With increasing stenosis severity the effect of magnetic field becomes more
      prominent. An externally applied magnetic field can improve haemodynamics
      perturbations in human coronary arteries, especially in the setting of moderate
      to-severe stenosis severity.

PMID- 29575960
TI  - Connective tissue growth factor expression after angiotensin II exposure is
      dependent on transforming growth factor-beta signaling via the canonical Smad
      dependent pathway in hypertensive induced myocardial fibrosis.
AB  - INTRODUCTION: Transforming growth factor-beta (TGF-beta) and connective tissue
      growth factor (CTGF) are often described as the initial pro-fibrotic mediators
      upregulated early in fibrosis models dependent on angiotensin II (Ang-II). In the
      present study, we explore the mechanistic link between TGF-beta and CTGF
      expression by using a novel TGF-beta trap. MATERIALS AND METHODS: NIH/3T3
      fibroblasts were subjected to TGF-beta with or without TGF-beta trap or 1D11
      antibody, CTGF or CTGF plus TGF-beta for six or 24 hours, and then used for
      quantitative real-time polymerase chain reaction (qRT-PCR) or
      immunocytochemistry. Male C57BL/6 mice were infused with Ang-II and randomly
      assigned TGF-beta trap for six or 24 hours. Hearts were harvested for
      histological analyses, qRT-PCR and western blotting. RESULTS: Exogenous TGF-beta
      induced fibroblasts resulted in significant upregulation of CTGF, TGF-beta and
      type I collagen transcript levels in vitro. Additionally, TGF-beta promoted the
      differentiation of fibroblasts into alpha-SMA+ myofibroblasts. CTGF expression
      was reduced by the addition of TGF-beta trap or neutralizing antibody, confirming
      that its expression is dependent on TGF-beta signaling. In contrast, exogenous
      CTGF did not appear to have an effect on fibroblast production of pro-fibrotic
      transcripts or fibroblast differentiation. Ang-II infusion in vivo led to a
      significant increase in TGF-beta and CTGF mRNA expression at six and 24 hours
      with corresponding changes in Smad2 phosphorylation (pSmad2), indicative of
      increased TGF-beta signaling. Ang-II animals that received the TGF-beta trap
      demonstrated reduced CTGF mRNA levels and pSmad2 at six hours, suggesting that
      early CTGF expression is dependent on TGF-beta signaling. CONCLUSIONS: We
      demonstrated that CTGF expression is dependent on TGF-beta signaling both in
      vitro and in vivo in a model of myocardial fibrosis. This also suggests that
      early myocardial CTGF mRNA expression (six hours) after Ang-II exposure is likely
      dependent on latent TGF-beta activation via the canonical Smad-dependent pathway
      in resident cardiac cells.

PMID- 29575962
TI  - Inhospital and delayed mortality after upper gastrointestinal bleeding: an
      analysis of risk factors in a prospective series.
AB  - BACKGROUND: Detailed analyses of mortality after upper gastrointestinal (GI)
      bleeding are lacking. Follow-up rarely extends beyond 30 days. AIMS: Our aim was
      to analyze in-hospital and delayed 6-months mortality, identifying risk factors.
      METHODS: This was a prospective study on patients with upper GI bleeding over 36
      months. Clinical outcomes were in-hospital and delayed-6 month-mortality.
      RESULTS: Four hundred and forty-none patients were included. Overall inpatient
      mortality was 9.8% but mortality directly related to bleeding was 5.1%. Patients
      who died presented lower systolic blood pressures, platelet recounts, prothrombin
      times and lower levels of hemoglobin, calcium, albumin, urea, creatinine and
      total proteins. Cirrhosis and neoplasms determined a higher in-hospital
      mortality. Albumin levels were protective, whereas creatinine and an active
      bleeding were risk factors for in-hospital death in multivariate analysis. Up to
      12.6% of patients discharged died in the first 6 months. Neoplasms, chronic
      kidney disease, coronary disease and esophageal varices were related to delayed
      mortality. Coronary disease and neoplasms were independent risk factors for
      mortality, but albumin levels were protective in multivariate analysis.
      CONCLUSION: Comorbidities were risk factors for delayed mortality, whereas
      albumin levels were a protective factor for in-hospital and delayed deaths. Six
      months mortality is proportionately as important as in-hospital mortality. Half
      of the delayed deaths might be preventable.

PMID- 29575964
TI  - Further considerations when addressing empathy in medical students.

PMID- 29575965
TI  - Atrial fibrillation in the Middle East: unmapped, underdiagnosed, undertreated.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the commonest persistent cardiac
      arrhythmia with an estimated incidence rate of between 1.5-2% and an important
      cause of strokes. Few epidemiological studies and clinical trials on the
      management of AF have been conducted outside Europe and North America. These gaps
      in our understanding of AF likely lead to sub-optimal management of patients with
      AF in the rest of the world. Areas covered: We discuss the epidemiology,
      treatment and clinical outcomes for AF in the Middle East after systematic review
      of published work for AF from the Middle East. We also discuss important clinical
      trials on AF conducted in the West in the same period to help contextualize our
      findings. Expert commentary: The few available Middle East studies suggest
      important epidemiological differences between Middle Eastern and Western AF
      populations. In particular, the Middle Eastern AF population is younger and have
      more co-morbidities than patients in the West. We find that significant numbers
      of moderate to high risk patients with AF are either undertreated or untreated
      placing them at increased risk of complications such as stroke. More studies in
      the Middle Eastern population are required to aid the development of region
      specific clinical guidelines to improve patient care.

PMID- 29575963
TI  - Innovations in asthma therapy: is there a role for inhaled statins?
AB  - INTRODUCTION: Asthma manifests as chronic airflow obstruction with persistent
      inflammation and airway hyperresponsiveness. The immunomodulatory and anti
      inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a.
      statins), suggest a therapeutic role in chronic inflammatory lung diseases.
      However, despite positive laboratory investigations and promising epidemiological
      data, clinical trials using statins for the treatment of asthma have yielded
      conflicting results. Inadequate statin levels in the airway compartment could
      explain these findings. Areas covered: HMGCR is in the mevalonate (MA) pathway
      and MA signaling is fundamental to lung biology and asthma. This article will
      discuss clinical trials of oral statins in asthma, review lab investigations
      relevant to the systemic versus inhaled administration of statins, address the
      advantages and disadvantages of inhaled statins, and answer the question: is
      there a role for inhaled statins in the treatment of asthma? Expert commentary:
      If ongoing investigations show that oral administration of statins has no clear
      clinical benefits, then repurposing statins for delivery via inhalation is a
      logical next step. Inhalation of statins bypasses first-pass metabolism by the
      liver, and therefore, allows for delivery of significantly lower doses to the
      airways at greater potency. Statins could become the next major class of novel
      inhalers for the treatment of asthma.

PMID- 29575966
TI  - An Unusual Case of Extensive Osseous Metaplasia in Fibroma of Ovary.

PMID- 29575967
TI  - The Authors reply: Factors influencing the educational impact of mini-CEX and
      DOPS.

PMID- 29575968
TI  - A Healthy, Chubby Japanese Man ( genki na debu chan).
AB  - In light of official reports indicating a still prevalent tendency to
      masculinized obesity and overweight in Japan (Ministry of Health Labour and
      Welfare, 2015), this article explores the experiences of 28 Japanese men
      grappling with bodyweight control. Aged between 24 and 67, 3 of the men were
      postgraduate or undergraduate students, 7 self-employed, 17 company workers and 1
      retired. Fourteen hold a university degree, 1 completed senior high school and 10
      finished 3-year junior college. Twelve were married and 16 were single. Ten of
      the participants have been requested to lose weight because of being at risk of
      developing metabolic diseases, the rest have been called "chubby" ( debu) and all
      of them have unsuccessfully tried to lose weight. A set of two, in-depth semi
      structured interviews were conducted with each participant in Tokyo and Osaka in
      June and July 2015, 2016, and 2017. Grounded in symbolic interactionism, the
      interview analysis allows for a reading of the participants' embodied
      subjectivity in line with three axes: autodidact self, gendered self, and
      emotional self. The article highlights how the feminization of care has an effect
      on the participant's daily interactions. In conclusion, the article underscores
      the salience of "emotional attachment" to food (Lupton, 1998, p. 158), the
      "emotionalization" of food consumption and the emotionalization of the "fat body"
      in understanding their experiences dealing with corpulence in a country where
      slimness appears to be "ethnicized."

PMID- 29575969
TI  - The Effect of Testosterone Replacement Therapy on Penile Hemodynamics in
      Hypogonadal Men With Erectile Dysfunction, Having Veno-Occlusive Dysfunction.
AB  - Hypogonadism may cause veno-occlusive dysfunction (VOD) by structural and
      biochemical alterations in the cavernosal tissue. The aim of the study was to
      investigate the effect of testosterone replacement therapy (TRT) on penile
      hemodynamics in hypogonadal men with erectile dysfunction and VOD. The study
      included 32 hypogonadal men with erectile dysfunction, having VOD. All patients
      underwent penile color Doppler ultrasonography (PCDU) at the beginning and 6
      months after the initial evaluation. Erectile function was evaluated with the 5
      item version of the International Index of Erectile Function (IIEF-5);
      hypogonadism was evaluated by testosterone measurement and the Aging Male
      Symptoms (AMS) scale. All patients received transdermal testosterone 50 mg/day
      for 6 months. Clinical and radiological findings were compared before and 6
      months after the TRT. The mean age was 58.81 +/- 4.56 (52-69) years. Mean total
      testosterone levels were 181.06 +/- 39.84 ng/dL and 509.00 +/- 105.57 ng/dL
      before and after the therapy, respectively ( p < .001). While all patients had
      physiological serum testosterone levels (>320 ng/dL) after the therapy, three
      cases (9.3%) had no clinical improvement of hypogonadism symptoms. Cavernosal
      artery peak systolic velocity (PSV) and resistive index (RI) significantly
      increased, and end diastolic velocity (EDV) significantly decreased after TRT.
      VOD no longer existed in 21 (65.6%) of the cases. This study demonstrated that
      TRT may restore penile hemodynamics in hypogonadal men with VOD.

PMID- 29575970
TI  - Medical Management of Endocarditis Caused by Stenotrophomonas maltophilia: A Case
      Report.
AB  - A 44-year-old female was found to be systemically ill at dialysis and admitted to
      the hospital. Days into the hospitalization, her blood cultures from dialysis
      were positive with Stenotrophomonas maltophilia bacteremia with a levofloxacin
      minimum inhibitory concentration (MIC) of 1. She was discharged on ciprofloxacin
      500 mg orally (PO) daily on hospital day 2 to complete a 14-day course. Weeks
      later, she was again found to be bacteremic at dialysis and sent back to the
      hospital. She was started on empiric antibiotics upon admission until further
      identification. Blood cultures again revealed S. maltophilia with a levofloxacin
      MIC of 32. Antibiotics were tailored to trimethoprim/sulfamethoxazole (TMP-SMX)
      until susceptibilities for additional agents were available. Further workup
      revealed mitral valve endocarditis. She was subsequently discharged on both
      minocycline 100 mg PO every 12 hours and TMP-SMX 1 DS PO daily with a planned
      duration of 6 weeks. Due to ongoing readmissions for hyperkalemia, TMP-SMX was
      discontinued and her regimen was modified to ceftazidime 1 g intravenously (IV)
      after HD plus minocycline 100 mg PO every 12 hours. She was deemed clinically and
      microbiologically cleared based on follow-up assessments. To our knowledge, this
      is the first case of S. maltophilia endocarditis treated with oral minocycline in
      combination with another antibiotic.

PMID- 29575971
TI  - Prognosis and related factors of HPV infections in postmenopausal Uyghur women.
AB  - With the aim to explore the characteristics of persistent HPV infections in
      postmenopausal Uyghur women and analyse the possible related risk factors, from
      September 2012 to September 2013; postmenopausal Uyghur women with HPV positive
      and pathologically diagnosed as non-cervical intraepithelial neoplasia (CIN)
      lesions and non-cervical cancer were recruited. Their clinical course was closely
      followed up for 24-36 months, and the risk factors were analysed by a logistic
      regression model. One hundred and sixteen positive women were followed for 36
      months. The total persistent HPV infection rate was 67.9%, and the type-specific
      persistent infection rate was 73.7% at 36 months. Nine (32.1%) women were
      naturally cleared of their HPV infection at 36 months. We found that an HPV16
      infection and an HPV58 infection, and time since menopause over 2 years were
      closely related with a persistent HPV infection. More attention should be paid to
      the women above 2 years of menopause who were infected with HPV16 and HPV58 in
      their further cervical carcinoma screening. Impact statement What is already
      known on this subject? Previous study revealed that menopause was a risk factor
      for a persistent HPV infection in Uyghur women. What do the results of this study
      add? The present study presented the characteristics of HPV persistent infection
      and the risk factors in Uyghur postmenopausal women. More attention should be
      paid to the women above 2 of years of menopause who are infected with HPV16 and
      HPV58. What are the implications of these findings for clinical practice and/or
      further research? This study would offer a theoretical basis for a better
      screening design, especially the women above 2 years' menopause who have been
      infected with HPV16 and HPV58 in the Xinjiang region.

PMID- 29575973
TI  - Mental Health Among Help-Seeking Urban Women: The Relationships Between Adverse
      Childhood Experiences, Sexual Abuse, and Suicidality.
AB  - Adverse childhood experiences (ACEs) and adult mental health were explored in a
      sample of urban Aboriginal ( n = 83) and non-Aboriginal ( n = 89) women.
      Childhood sexual abuse (CSA) was associated with negative home environments,
      teenage pregnancy, lifetime suicide attempts, and treatment seeking. Aboriginal
      women with CSA witnessed higher levels of physical/sexual abuse of family
      members. The severity of current psychological distress was associated with a
      history of childhood neglect. The results indicate that CSA rarely occurs in
      isolation, and that multiple ACEs are strongly associated with suicide attempts
      and treatment seeking in adulthood. Future studies should focus on the role of
      CSA in suicidality, as well as familial, community, and cultural protective
      factors.

PMID- 29575972
TI  - Pulmonary arterial hypertension and atrial arrhythmias: incidence, risk factors,
      and clinical impact.
AB  - Atrial arrhythmia (AA) occurrence in pulmonary arterial hypertension (PAH) may
      determine clinical deterioration and affect prognosis. In this study we assessed
      AA incidence in idiopathic (IPAH) and systemic sclerosis related PAH (SSc-PAH)
      and evaluated risk factors, management, and impact on mortality. We collected
      baseline data from consecutive IPAH or SSc-PAH patients prospectively enrolled in
      the Johns Hopkins Pulmonary Hypertension Registry between January 2000 and July
      2016. During follow-up AA onset, treatment, and outcome were recorded. Among 317
      patients (201 SSc-PAH, 116 IPAH), 42 developed AA (19 atrial fibrillation, 10
      flutter-fibrillation, 9 atrial flutter, and 4 atrial ectopic tachycardia) with a
      13.2% cumulative incidence. Most events were associated with hospitalization
      (90.5%). Electrical or pharmacological cardioversion was attempted in most cases.
      Patients with AA had higher right atrial pressure, pulmonary wedge pressure ( P <
      0.005), NT-proBNP ( P < 0.05), and thyroid disease prevalence ( P < 0.005).
      Higher mortality was observed in patients with AA, though not statistically
      significant (LogRank P = 0.323). Similar long-term mortality between IPAH with AA
      and SSc-PAH without AA was observed (LogRank P = 0.098). SSc-PAH with AA had the
      worst prognosis. In PAH patients AA occurrence is a matter of significant
      concern. Therapeutic strategies aimed at restoring sinus rhythm may represent an
      important goal.

PMID- 29575974
TI  - Minority healthcare providers experience challenges, trust, and interdependency
      in a multicultural team.
AB  - BACKGROUND: The nursing community in the Nordic countries has become
      multicultural because of migration from European, Asian and African countries. In
      Norway, minority health care providers are recruited in to nursing homes which
      have become multicultural workplaces. They overcome challenges such as language
      and strangeness but as a group they are vulnerable and exposed to many
      challenges. PURPOSE: The aim is to explore minority healthcare providers, trained
      nurses and nurses' assistants, and their experiences of challenges when working
      in a multicultural team in a Norwegian context. RESEARCH METHOD: The study has a
      qualitative design, using narrative interviews, and a phenomenological
      hermeneutic analysis method to explore the experiences of challenges in dementia
      care. Ethical considerations: The study was approved by The Norwegian Regional
      Ethics Committee, and the Norwegian Social Science Data Services. Participation
      and research context: Five informants from different African, Asian and European
      countries participated in the study. The study was conducted in a Norwegian
      nursing home, in a dementia care unit. FINDINGS: The results show that minority
      health care providers experience and find meaning in being a member of a team,
      they overcome challenges, characterized by the interdependency in the team,
      appreciating new cultural experiences and striving to belong. They must overcome
      challenges such as language problems and the feeling of strangeness. DISCUSSION:
      The findings are discussed considering Logstrup's ethic of proximity, the ethical
      demand of trust, and interdependency. The ethical demand is an answer to a
      common, transparent, unspoken agreement to be met, seen, and understood.
      CONCLUSION: The study shows that cooperation in a multi-professional and multi
      ethnic team is important, and secures the quality of care to persons with
      dementia. Further research is necessary to examine the relation between a multi
      ethnic staff and the patients experiencing dementia. Further research is
      necessary to examine ethnicity, the relation between a multi-ethnic staff, the
      patients experiencing dementia and next of kin.

PMID- 29575975
TI  - Oxidative stress in elite athletes training at moderate altitude and at sea
      level.
AB  - Using a controlled parallel group longitudinal trial design, we investigated the
      effects of different training interventions on the prooxidant/antioxidant status
      of elite athletes: living and training at moderate altitude for 3 (Hi-Hi3) and 4
      weeks (Hi-Hi), and for 4 weeks too, living high and training high and low (Hi
      HiLo) and living and training at sea level (Lo-Lo). From 61 swimmers, 54
      completed the study. Nitrites, carbonyls, and lipid peroxidation (LPO) levels
      were assessed in plasma. Enzymatic antioxidants glutathione peroxidase (GPx) and
      glutathione reductase (GRd), and non-enzymatic antioxidants total glutathione
      (GST), reduced glutathione (GSH) and oxidized glutathione (GSSG) were analysed in
      the erythrocyte fraction. At the end of the intervention, nitrites levels were
      similar in all altitude groups but higher than in the Lo-Lo controls (P = .02).
      Hi-HiLo had greater GPx activity than Hi-Hi and Hi-Hi3 during most of the
      intervention (P <= .001). GRd activity was higher in Lo-Lo than in Hi-Hi at the
      end of the training camp (P <= .001). All groups showed increased levels of LPO,
      except Lo-Lo, and carbonyls at the end of the study (P <= .001). Training at
      altitude for 3 or 4 weeks drives oxidative stress leading to cellular damage
      mainly by worsening the antioxidant capacities. The GSSG/GSH ratio appears to be
      related to perceived exertion and fatigue. The stronger antioxidant defence
      showed by the Hi-HiLo group suggests an inverse relationship between redox
      alterations and performance. Further studies are required to investigate the role
      of oxidative stress in acclimatization, performance, and health.

PMID- 29575976
TI  - The effects of autobiographical memory and visual perspective on working memory.
AB  - The present research aims to explore whether recalling and writing about
      autobiographical memory from different perspectives (first-person perspective vs.
      third-person perspective) could affect cognitive function. The participants first
      performed a working memory task to evaluate their working memory capacity as a
      baseline and then were instructed to recall (Study 1) or write about (Study 2)
      personal events (failures vs. successes) from the first-person perspective or the
      third-person perspective. Finally, they performed the working memory task again.
      The results suggested that autobiographical memory and perspective influence
      working memory interactively. When recalling a success, the participants who
      recalled from the third-person perspective performed better than those who
      recalled from the first-person perspective on the working memory capacity task;
      when recalling a failure, the opposite was true.

PMID- 29575978
TI  - Decreasing dialysis catheter rates by creating a multidisciplinary dialysis
      access program.
AB  - INTRODUCTION:: Centers for Medicare and Medicaid Services have determined that
      chronic dialysis units should have <12% of their patients utilizing central
      venous catheters for hemodialysis treatments. On the Eastern Shore of Maryland,
      the central venous catheter rates in the dialysis units averaged >45%. A
      multidisciplinary program was established with goals of decreasing catheter rates
      in order to decrease central line-associated bloodstream infections, decrease
      mortality associated with central line-associated bloodstream infection, decrease
      hospital days, and provide savings to the healthcare system. METHODS:: We
      collected the catheter rates within three dialysis centers served over a 5-year
      period. Using published data surrounding the incidence and related costs of
      central line-associated bloodstream infection and mortality per catheter day, the
      number of central line-associated bloodstream infection events, the costs, and
      the related mortality could be determined prior to and after the initiation of
      the dialysis access program. RESULTS:: An organized dialysis access program
      resulted in a 82% decrease in the number of central venous catheter days which
      lead to a concurrent reduction in central line-associated bloodstream infection
      and deaths. As a result of creating an access program, central venous catheter
      rates decreased from an average rate of 45% to 8%. The cost savings related to
      the program was calculated to be over US$5 million. The decrease in the number of
      mortalities is estimated to be between 13 and 27 patients. CONCLUSION:: We
      conclude that a formalized access program decreases catheter rates, central line
      associated bloodstream infection, and the resultant hospitalizations, mortality,
      and costs. Areas with high hemodialysis catheter rates should develop access
      programs to better serve their patient population.

PMID- 29575977
TI  - Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS.
AB  - Experimental models of sepsis in small and large animals and a variety of in
      vitro preparations have established several basic mechanisms that drive
      endothelial injury. This review is focused on what can be learned from the
      results of clinical studies of plasma biomarkers of endothelial injury and
      inflammation in patients with sepsis. There is excellent evidence that elevated
      plasma levels of several biomarkers of endothelial injury, including von
      Willebrand factor antigen (VWF), angiopoietin-2 (Ang-2), and soluble fms-like
      tyrosine kinase 1 (sFLT-1), and biomarkers of inflammation, especially
      interleukin-8 (IL-8) and soluble tumor necrosis factor receptor (sTNFr), identify
      sepsis patients with a higher mortality. There are also some data that elevated
      levels of endothelial biomarkers can identify which patients with non-pulmonary
      sepsis will develop acute respiratory distress syndrome (ARDS). If ARDS patients
      are divided among those with indirect versus direct lung injury, then there is an
      association of elevated levels of endothelial biomarkers in indirect injury and
      markers of inflammation and alveolar epithelial injury in patients with direct
      lung injury. New research suggests that the combination of biologic and clinical
      markers may make it possible to segregate patients with ARDS into hypo- versus
      hyper-inflammatory phenotypes that may have implications for therapeutic
      responses to fluid therapy. Taken together, the studies reviewed here support a
      primary role of the microcirculation in the pathogenesis and prognosis of ARDS
      after sepsis. Biological differences identified by molecular patterns could
      explain heterogeneity of treatment effects that are not explained by clinical
      factors alone.

PMID- 29575979
TI  - Importance of the integrated test in the Down's syndrome screening algorithm.
AB  - OBJECTIVE: In the Czech Republic, over 97% of all pregnant women undergo some
      type of antenatal screening for Down's syndrome. In about 95% of cases with a
      confirmed fetal chromosomal abnormality, the pregnancy is terminated. The most
      commonly used test is the first trimester combined test. We investigated the
      impact of implementing an integrated sequential test to improve the detection of
      Down's syndrome pregnancies. METHODS: Data on the incidence of congenital
      defects, number of births, and affected pregnancies terminated are recorded in
      the National Registry of Congenital Anomalies. Anonymous data on cases of Down's
      syndrome diagnosed antenatally or postnatally between 2010 and 2015 in one of the
      large antenatal care centers were analyzed. RESULTS: There were 600 diagnoses of
      Down's syndrome (5.7 per 1000 births), 90% of which were made antenatally. Of
      antenatally detected cases, 80% were indicated for diagnostic procedure by
      multimarker screening results. In the multimarker screen positive group, 75%
      cases were first trimester positive and 25% second trimester positive (most of
      these had positive integrated test results). Among Down's syndrome cases
      indicated for antenatal diagnosis by multimarker screening results 6.25% (n = 26)
      were first trimester negative, and became positive after integration with the
      second trimester screening results. CONCLUSIONS: Results from five major Czech
      antenatal centers confirm that an integrated sequential test would detect 80-85%
      of Down's syndrome fetuses in the first trimester and at least an extra 5-10% of
      Down's syndrome pregnancies in the second trimester of pregnancy. These are
      important data that should be considered in implementing the national antenatal
      screening program.

PMID- 29575980
TI  - Atrazine affects craniofacial chondrogenesis and axial skeleton mineralization in
      zebrafish ( Danio rerio).
AB  - Atrazine is a commonly used herbicide that has previously been implicated as an
      endocrine-disrupting compound. Previous studies have shown that estrogenic
      endocrine-disrupting compounds affect the development of the heart, cartilage,
      and bone in zebrafish ( Danio rerio). To determine whether atrazine has effects
      similar to other endocrine disruptors, zebrafish embryos were treated with a
      range of atrazine concentrations. Atrazine treatment at a low concentration of
      0.1 uM resulted in significant differences in craniofacial cartilage elements,
      while concentrations >=1 uM led to decreased survival and increased heart rates.
      Fish treated with >=1 uM atrazine also developed with delayed vertebrae
      mineralization. Higher concentrations of atrazine caused gross craniofacial
      defects and decreased hatching rates. Further studies into the molecular pathways
      disrupted in these developmental processes could shed light on a link between
      endocrine-disrupting compounds and developmental abnormalities.

PMID- 29575981
TI  - Endobag separation - an ominous sign after endovascular aneurysm sealing with the
      Nellix device.
AB  - Our report aims to alert physicians performing endovascular aneurysm sealing with
      the Nellix endoprosthesis to the risk of rupture when endobag separation is
      noticed on computed tomography. Endobag separation when observed with acute
      presentation of abdominal pain is an indicator of imminent rupture and prompt
      interventional treatment should be undertaken.

PMID- 29575982
TI  - A Diabetes Mobile App With In-App Coaching From a Certified Diabetes Educator
      Reduces A1C for Individuals With Type 2 Diabetes.
AB  - Purpose There are currently many diabetes apps available, but there is limited
      evidence demonstrating clinical impact. The purpose of this study is to evaluate
      the impact of a diabetes mobile app with in-app coaching by a certified diabetes
      educator on glycemic control for individuals with type 2 diabetes. Methods A 12
      week-long single-arm intent-to-treat trial evaluated the impact of a diabetes
      mobile app and coaching program (One Drop | Mobile With One Drop | Experts),
      which facilitated tracking of self-care and included an in-app diabetes education
      program, on A1C for individuals with type 2 diabetes and an A1C >=7.5% (58
      mmol/mol). An online study platform (Achievement Studies, Evidation Health Inc,
      San Mateo, CA) was used to screen, consent, and enroll participants; collect
      study data; and track participants' progress throughout the study. Baseline and
      study end A1C measurements as well as questionnaire data from participants were
      collected. Results Participants (n = 146) were 52 +/- 9 years old, 71% female,
      25% black or Hispanic, diagnosed with diabetes for 11 +/- 7 years, and with a
      mean baseline A1C of 9.87% +/- 2.0 (84 mmol/mol). In adjusted repeated measures
      models, mean A1C improved by -0.86% among study completers (n = 127), -0.96%
      among active users of the app and coaching program (n = 93), and -1.32% among
      active users with a baseline A1C >=9.0% (75 mmol/mol) (n = 53). Conclusions This
      program was associated with a clinically meaningful and significant reduction in
      A1C and can potentially increase access to effective diabetes self-management
      education and support for individuals with diabetes.

PMID- 29575983
TI  - Associative Attitude Learning: A Closer Look at Evidence and How It Relates to
      Attitude Models.
AB  - Associative attitude learning is typically viewed as a low-level process that
      automatically registers mere co-occurrences between stimuli, independent of their
      validity and relational meaning. This view invites to critically examine how
      attitude formation conforms to four operating conditions (i.e., unawareness,
      efficiency, goal independence, and uncontrollability) and two operating
      principles (i.e., unqualified registration of mere co-occurrences between stimuli
      and formation of direct stimulus-response links), which is the main purpose of
      the present contribution. The general discussion examines how contemporary
      attitude models endorse these conditions and principles. Overall, this
      contribution calls for (a) a nuanced understanding of the nature and scope of
      associative attitude learning, (b) a fine-grained understanding of how
      contemporary attitude models endorse conditions and principles reviewed here and
      find them relevant to their theorization of attitude formation,

PMID- 29575984
TI  - Population modification of Anopheles mosquitoes for malaria control: pathways to
      implementation.

PMID- 29575985
TI  - Successful treatment of severe combined post- and pre-capillary pulmonary
      hypertension in a patient with idiopathic restrictive cardiomyopathy.
AB  - Restrictive cardiomyopathy (RCM) is a rare form of cardiomyopathy that is
      characterized by restrictive ventricular filling. Elevated filling pressure leads
      to pulmonary hypertension (PH), which often progresses to combined post- and pre
      capillary PH (Cpc-PH) with increased diastolic pulmonary vascular pressure
      gradient (DPG) and pulmonary vascular resistance (PVR) caused by longstanding
      backward hemodynamic consequences of left heart disease (LHD) leading to
      morphological changes in the pulmonary vasculature. Patients with high PVR
      undergoing left ventricular assist device (LVAD) implantation are at increased
      risk of postoperative right-sided heart failure requiring concomitant
      implantation of a right ventricular assist device (RVAD). We report a case of RCM
      with severe Cpc-PH due to extremely elevated DPG and PVR. The patient presented
      recurrent syncope caused by severe PH. Right heart catheterization (RHC) revealed
      highly elevated DPG 30 mmHg and PVR 25.3 Wood units (WU) and subsequent
      significant reduction of right ventricular afterload during vasoreactivity
      testing with inhaled nitric oxide (NO) to DPG 5 mmHg and PVR 10.5 WU. During the
      administration of pulmonary vasodilators, pulmonary congestion worsened. Second
      RHC revealed elevated pulmonary arterial wedge pressure (PAWP) and modest
      decrease of pulmonary arterial pressure (PAP) 87 mmHg and PVR 9.6 WU. Therefore,
      an inotropic agent and systemic vasodilator were added for the treatment of left
      sided heart failure. Targeting elevated filling pressures with both PAH-specific
      and heart failure treatment, a further decrease of right ventricular afterload
      with DPG of 5 mmHg and PVR of 3.8 WU was achieved. In a next step, LVAD was
      successfully implanted, without need for RVAD, as a bridge to transplantation.
      This is the first reported case of Cpc-PH that revealed the potential
      reversibility of extremely elevated DPG and PVR, and suggests the importance of
      preoperative RHC-guided optimized medical PAH-specific and heart failure
      treatment before LVAD implantation.

PMID- 29575986
TI  - Nutrient salt removal by steel-making slag in sediment microbial fuel cells.
AB  - Applying sediment microbial fuel cells (SMFCs) into sediment can remediate the
      sediment; however, nutrient salts cannot be removed by SMFCs effectively. In this
      study, sediment mixed with steel-making slag is used a fuel in SMFCs for
      understanding the potential of steel-making slag in nutrient salt removal in
      SMFCs. To the best of our knowledge, no report related to the use of steel-making
      slag in SMFCs is found in the literature. The combination of SMFCs with steel
      making slag is expected to make the individual efficiency of SMFCs and steel
      making slag more reactive, and is another way to increase the benefit of using
      steel-making slag. Experimental results showed that steel-making slag was more
      effective for adsorbing nutrient salts in SMFCs. Interestingly, the combination
      of SMFCs with steel-making slag can increase the individual efficiency of SMFCs
      and steel-making slag.

PMID- 29575987
TI  - Network meta-analysis in health psychology and behavioural medicine: a primer.
AB  - Progress in the science and practice of health psychology depends on the
      systematic synthesis of quantitative psychological evidence. Meta-analyses of
      experimental studies have led to important advances in understanding health
      related behaviour change interventions. Fundamental questions regarding such
      interventions have been systematically investigated through synthesising relevant
      experimental evidence using standard pairwise meta-analytic procedures that
      provide reliable estimates of the magnitude, homogeneity and potential biases in
      effects observed. However, these syntheses only provide information about whether
      particular types of interventions work better than a control condition or
      specific alternative approaches. To increase the impact of health psychology on
      health-related policy-making, evidence regarding the comparative efficacy of all
      relevant intervention approaches - which may include biomedical approaches - is
      necessary. With the development of network meta-analysis (NMA), such evidence can
      be synthesised, even when direct head-to-head trials do not exist. However, care
      must be taken in its application to ensure reliable estimates of the effect sizes
      between interventions are revealed. This review paper describes the potential
      importance of NMA to health psychology, how the technique works and important
      considerations for its appropriate application within health psychology.

PMID- 29575988
TI  - Mycotoxins in infant/toddler foods and breakfast cereals in the US retail market.
AB  - The objective of this study was to conduct a mycotoxin survey of commercial
      infant/toddler foods (cereals and teething biscuits) and breakfast cereals in the
      United States. A total of 215 retail samples were collected from three
      geographical locations and analysed for aflatoxins, fumonisins, deoxynivalenol,
      HT-2 toxin, ochratoxin A, T-2 toxin, and zearalenone using a stable isotope
      dilution liquid-chromatography tandem mass spectrometry (LC-MS/MS) method. One or
      more mycotoxins were found in 69% (101/147) of the infant/toddler foods and 50%
      (34/68) of breakfast cereals. Mycotoxin co-occurrence was observed in 12% of
      infant/toddler foods and 32% of breakfast cereals. However, the concentrations of
      detected mycotoxins were lower than the current FDA action and guidance levels.
      Aflatoxins and HT-2 toxin were not detected in any of the samples, while
      deoxynivalenol was the most frequently detected mycotoxin. Rice-based cereals
      appeared to be less susceptible to mycotoxin contamination than other cereal
      types.

PMID- 29575989
TI  - Financial impact of oral chemotherapy wastage on society and the patient.
AB  - Background Targeted oral agents are now increasingly being utilized in cancer
      treatment, but are expensive. Changing the dose of these medications due to
      toxicity or discontinuation secondary to disease progression or death causes
      waste from unused medication. Limiting waste is an important goal, as waste has a
      substantial financial impact on patients and insurance companies. Methods
      Patients started on oral targeted agents' sunitinib, everolimus, axitinib, or
      vemurafenib between January 2012 and February 2015 who obtained their medications
      at Holden Comprehensive Cancer Center specialty pharmacy were included in the
      analysis. We acquired dispensing data retrospectively for each of the agents and
      reviewed patient charts. Wasted tablets/capsules were calculated from their last
      fill to the dates of stoppage or dose adjustment. The amount associated with the
      wastage was calculated using the average wholesale price. Repository drug usage
      data during the same time period was obtained. Results Eighty-eight patients had
      their prescriptions filled at Holden Comprehensive Cancer Center during the study
      time period. Waste occurred in 41% of all patients with primary reasons
      attributed to cancer progression in 25 patients, death in five patients, toxicity
      in five patients and increase in dosage of targeted therapy in two patients. A
      total of 1179 tablets or capsules were wasted from all causes, priced at a total
      of $248,595.69. Conclusion Oral chemotherapy medications are associated with
      wastage, which is a significant financial burden to society. Progression of
      disease emerged as the single most important factor accounting for wastage. Novel
      ideas are needed to prevent wastage, thereby reducing healthcare costs.

PMID- 29575991
TI  - Commentary: Imaging of Endograft Apposition, Position, and Expansion in the
      Aortic Neck Following EVAR: Evaluation of a Novel Concept to Predict Type Ia
      Endoleak.

PMID- 29575990
TI  - The effectiveness of cortico-cortical evoked potential in detecting seizure onset
      zones.
AB  - Objective The aim of the study was to evaluate the parameters for localizing the
      seizure onset zone in refractory epilepsy patients using cortico-cortical evoked
      potentials (CCEP). Methods Fifteen patients (nine females) with medically
      refractory partial epilepsy underwent stereo electro encephalography (SEEG) in
      Tsinghua University Yu-Quan Hospital from 2015 to 2016. Clinical semiology and,
      scalp electroencephalography (EEG) findings were analyzed during phase I
      preoperative evaluation. During phase II evaluation, localization of seizure
      onset zone (SOZ) was analyzed using SEEG by experienced epileptologists.
      Meanwhile, the cortico-cortical evoked potential (CCEP) paradigm was tested in
      all patients in phase II. The value of root-mean-square (RMS) of CCEPs amplitude
      from 7 ms to 300 ms after stimulation was analyzed to quantify the response.
      Results RMS of CCEPs amplitude in SOZ was higher than in seizure propagation zone
      (SPZ) (P < 0.05) and non-seizure onset zone (NSOZ) (P < 0.05). RMS of CCEPs
      amplitude in SOZ was higher than in NSOZ in epilepsy patients with secondary
      generalized tonic-clonic seizures (SGTCS) (N = 6, P < 0.05); The RMS of CCEPs
      amplitude in SOZ was strikingly higher than SPZ in the repetitive spiking (RS)
      onset pattern, and the difference was significant (N = 5, P < 0.01). Conclusions
      This data indicated that CCEP response is enhanced in SOZ despite different
      seizure types (with or without SGTCS). CCEP may be an effective method to locate
      SOZ.

PMID- 29575992
TI  - Below-the-Knee Retrograde Access for Peripheral Interventions: A Systematic
      Review.
AB  - PURPOSE: To investigate the hypothesis that interventions involving retrograde
      below-the-knee (BTK) vessel punctures have an acceptably low complication rate
      and high procedural success. METHODS: A systematic review was performed of the
      MEDLINE and Scopus databases for articles describing the results of BTK
      retrograde access for peripheral interventions. Outcome measures were access
      success, procedure success, and complications. A predefined subgroup analysis was
      performed of prospective studies to reduce the influence of possible reporting
      bias on outcomes. RESULTS: Nineteen articles, including 3 prospective studies,
      were selected, including a total of 1905 interventions in 1395 patients (mean age
      69.5 years; 918 men). The BTK vessels were punctured in 1168 (61.3%) of these
      interventions. Access was successful in 94.0% of BTK attempts, 86.0% of all
      lesions were successfully crossed using a retrograde access, and 84.0% of
      interventions achieved technical success. Forty-eight (4.1%) distal access site
      complications were reported. Vessel perforations were seen in 13 (1.1%)
      interventions, vasospasm in 5 (0.4%), and acute distal occlusions in 5 (0.4%).
      Predefined subgroup analysis of prospective studies showed similar results
      (p=0.24). CONCLUSION: A retrograde approach to facilitate peripheral endovascular
      interventions is a safe and successful technique and should be considered when an
      antegrade approach is not possible or fails to cross the lesion. Because of
      missing data on long-term outcomes and methodological shortcomings, real world
      data of retrograde access in nonexpert centers remains necessary before this
      technique can be advised to all interventionists dealing with peripheral artery
      disease.

PMID- 29575993
TI  - Determination of Endograft Apposition, Position, and Expansion in the Aortic Neck
      Predicts Type Ia Endoleak and Migration After Endovascular Aneurysm Repair.
AB  - PURPOSE: To describe the added value of determining changes in position and
      apposition on computed tomography angiography (CTA) after endovascular aneurysm
      repair (EVAR) to detect early caudal displacement of the device and to prevent
      type Ia endoleak. METHODS: Four groups of elective EVAR patients were selected
      from a dataset purposely enriched with type Ia endoleak and migration (>10 mm)
      cases. The groups included cases of late type Ia endoleak (n=36), migration
      (n=9), a type II endoleak (n=16), and controls without post-EVAR complications
      (n=37). Apposition of the endograft fabric with the aortic neck, shortest
      distance between the fabric and the renal arteries, expansion of the main body
      (or dilatation of the aorta in the infrarenal sealing zone), and tilt of the
      endograft toward the aortic axis were determined on the first postoperative and
      the last available CTA scan without type Ia endoleak or migration. Differences in
      these endograft dimensions were compared between the first vs last scan and among
      the 4 groups. RESULTS: No significant differences in endograft configurations
      were observed among the groups on the first postoperative CTA scan. On the last
      CTA scan before a complication arose, the position of the fabric relative to the
      renal arteries, expansion of the main body, and apposition of the fabric with the
      aortic neck were significantly different between the type Ia endoleak (median
      follow-up 15 months) and migration groups (median follow-up 23 months) compared
      with the control group (median follow-up 19 months). Most endograft dimensions
      had changed significantly compared with the first postoperative CTA scan for all
      groups. Apposition had increased in the control group but had decreased
      significantly in the type Ia endoleak and migration groups. CONCLUSION:
      Progressive changes in dimensions of the endograft within the infrarenal neck
      could be detected on regular CTA scans before the complication became urgent in
      many patients.

PMID- 29575996
TI  - Soleus H-Reflex and Its Modulation With Vibration in Idiopathic Toe Walkers and
      Typically Developing Children.
AB  - Idiopathic toe walking is a relatively common developmental condition often
      leading to secondary problems such as pain and muscle contractures in the lower
      extremities. The cause of idiopathic toe walking is unknown, which hinders the
      development of treatment strategies. To test whether children with idiopathic toe
      walking have functional alterations in their spinal motor circuits, we studied
      the properties of the soleus H-reflex and its modulation with vibration in 26
      idiopathic toe walkers and 16 typically developing children. At the group level,
      the H-reflex properties did not differ, but at the individual level, in 7 of 25
      idiopathic toe walkers, some of the H-reflex parameters fell out of normal limits
      of typically developing children. However, the H-reflex was suppressed by
      vibration to the Achilles tendon similarly in both the idiopathic toe walkers and
      typically developing children. In conclusion, idiopathic toe walking in some
      children can be associated with functional alterations in their spinal motor
      circuits.

PMID- 29575995
TI  - Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain
      Tumor Survivors.
AB  - Among childhood cancer survivors, increased stroke risk after cranial radiation
      therapy may be caused by radiation-induced arteriopathy, but limited data exist
      to support this hypothesis. Herein, we assess the timing and presence of cerebral
      arteriopathy identified by magnetic resonance angiography (MRA) after cranial
      radiation therapy in childhood brain tumor survivors. In a cohort of 115
      pediatric brain tumor survivors, we performed chart abstraction and prospective
      annual follow-up to assess the presence of large vessel cerebral arteriopathy by
      MRA. We identified 10 patients with cerebral arteriopathy. The cumulative
      incidence of arteriopathy 5 years post-cranial radiation therapy was 5.4% (CI
      0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial
      ischemic stroke 2.4 years post-cranial radiation therapy in the distribution of a
      radiation-induced stenotic artery. We conclude that large vessel arteriopathies
      can occur within a few years of cranial radiation therapy and can become apparent
      on MRA in under a year.

PMID- 29575997
TI  - 1,25(OH)2D3 Protects Trophoblasts Against Insulin Resistance and Inflammation Via
      Suppressing mTOR Signaling.
AB  - Gestational diabetes mellitus (GDM) is the primary cause of maternal and fetal
      morbidity and mortality. Insulin resistance (IR) is pivotal to GDM pathogenesis,
      and mammalian target of rapamycin (mTOR) is a critical regulator of GDM. An
      increasing amount of evidence indicates that vitamin D deficiency is a risk
      factor for GDM. However, there are few reports on the effect of IR on GDM
      placentas. The present study aims to verify that 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) can ameliorate trophoblast IR by suppressing mTOR signaling. An IR
      BeWo cell model was established in the presence of high insulin and glucose
      medium. The IR level and mTOR activation with or without 1,25(OH)2D3 treatment
      were evaluated. The IR cells exhibited excessive mTOR signaling activation,
      upregulated inflammatory factor levels, and extensive lipid infiltration.
      However, 1,25(OH)2D3 reversed mTOR activation and reduced the IR level and lipid
      infiltration. In addition, 1,25(OH)2D3 treatment in GDM placental explants
      blocked the aberrant, increased levels of leptin, TNF-alpha, and IL-6. Therefore,
      1,25(OH)2D3 treatment protects trophoblasts against high IR mainly through
      suppressing mTOR signaling, and this mechanism may serve as a potential therapy
      for patients with GDM.

PMID- 29575998
TI  - Human Endometrial Reconstitution From Somatic Stem Cells: The Importance of Niche
      Like Cells.
AB  - Endometrial regeneration has long been proposed to be mediated by stem cells, but
      the isolation of endometrial stem cells has been hampered by a lack of validated
      markers. Specific markers would enable isolation of these stem cells, thereby
      promoting advancements in regenerative medicine for the treatment of endometrial
      diseases and dysfunctions. We sought to investigate the regenerative ability of
      human endometrial positive for sushi domain containing 2/intercellular adhesion
      molecule 1 (SUSD2+/ICAM1+) cells and Side Population cell lines in a xenograft
      mice model. The injection of total endometrial cell suspensions and Side
      Population cell lines under kidney capsules induced neoformation of human
      endometrium verified by the presence of typical endometrial markers (vimentin,
      cytokeratin 18, and progesterone receptor) by immunofluorescence. Total
      endometrial cell types promoted a better reconstitution in comparison to
      injecting ICAM1+ and SUSD2+ cells alone. The endometrial fraction is probably
      acting as a niche, resulting in increased reconstruction efficiency of pure
      fractions. Human engrafted cells were localized near blood vessels and induced
      the proliferation of surrounding cells. Our results suggest that human
      endometrial Side Population, a heterogeneous population possibly harboring
      endometrial stem cells, has the optimum capacity to regenerate endometrial-like
      tissue. In contrast, cells positive for single stem cell markers SUSD2 and ICAM1
      have minimally functional regenerative capacities in the absence of niche-like
      cells.

PMID- 29575999
TI  - Epigenetic Drugs in the Treatment of Endometriosis.

PMID- 29576000
TI  - Uterine Autotransplantation in the Nonhuman Primate With Preservation of the
      Uterine and Ovarian Vascular Pedicles.
AB  - PURPOSE: To evaluate the technical feasibility of performing a uterine
      autotransplantation in the nonhuman primate while preserving the uterine and
      ovarian vascular pedicles. METHODS: Eight (n = 8) female baboons at a primate
      research facility underwent a uterine autotransplant procedure with preservation
      of the vascular pedicles. The uterine arteries were separated from their
      amorphous tissue and skeletonized toward the internal iliac arteries bilaterally.
      A segment of the internal iliac artery was removed bilaterally along with both
      uterine arteries. Both ovarian veins were preserved to assist with the
      reperfusion of the uterine organ. Due to larger vascular pedicles in one of the
      primates, the uterine arteries were separated and reattached directly via end-to
      end anastomosis. In another baboon, the deep uterine vein was used as a vascular
      pedicle rather than the ovarian vein on the left side due to adequate size and
      visualization. RESULTS: Immediate tissue reperfusion occurred intraoperatively in
      5 of the animals, with slower perfusion in 3 of the animals. Average warm
      ischemia time was 43.8 minutes while the average cold ischemia time was 174
      minutes (2 hours, 54 minutes). Average total surgical time was 5.9 hours. All
      animals were sheltered into separate cages and monitored for behavior changes and
      food and drink consumption. Three of the primates expired immediately
      postoperatively, 2 from severe dehydration and 1 from gastric aspiration.
      CONCLUSIONS: This pilot study describes a modified surgical approach for uterine
      transplants in the nonhuman primate. This surgical technique may be applicable to
      living and deceased donor uterine transplantation.

PMID- 29576001
TI  - Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic
      Ovary Syndrome: A Randomized Double-Blind Controlled Trial.
AB  - OBJECTIVES: To evaluate the impact of metformin on in vitro fertilization (IVF)
      outcomes in overweight and obese women with polycystic ovary syndrome (PCOS).
      METHODS: This was a randomized double-blind placebo-controlled study (
      ClinicalTrials.gov : NCT 02910817) carried out in a University IVF Center. The
      study included 102 overweight and obese women (body mass index [BMI] >24 kg/m2)
      with PCOS who underwent their first fresh autologous IVF-embryo transfer cycle
      and agreed to participate in the study. The study participants were randomized
      into 2 groups: metformin group received metformin (1000 mg per day) at the start
      of controlled ovarian stimulation (COH) until the day of the pregnancy check, and
      placebo group received placebo tablets in the same duration. The primary outcome
      measure was the total number of retrieved oocytes. RESULTS: Both groups were
      homogenous in baseline demographic characteristics. Metformin group versus the
      placebo group demonstrated decrease in the mean number of the retrieved oocytes
      (9.06 +/- 4.23 vs 16.86 +/- 8.3, P < .01) and similar live birth rate (LBR; 25.5%
      vs 17.6%, P = .34). The number of fertilized oocytes was lower in the metformin
      group (5.65 +/- 2.66 vs 9 +/- 4.55, P < .01). However, the fertilization rate was
      similar in both groups (62.3% vs 53.4%, P = .10). There was no difference in the
      implantation rate (15.7% vs 11.8%, P = .32), multiple pregnancy rate (13.4% vs
      3.9%, P = .08), or miscarriage rate (23.5% vs 35.7%, P = .46). No cases of
      ovarian hyperstimulation syndrome (OHSS) were observed in both groups.
      CONCLUSION: Short-term administration of metformin to overweight or obese women
      with PCOS undergoing IVF decreased number of the retrieved oocytes but did not
      improve the LBR. Synopsis Metformin use could decrease the number of retrieved
      oocytes in overweight and obese women with polycystic ovary syndrome undergoing
      IVF.

PMID- 29576002
TI  - Diminished Frequency of Menstrual and Peripheral Blood NKT-Like Cells in Patients
      With Unexplained Recurrent Spontaneous Abortion and Infertile Women.
AB  - Systemic monitoring of immune system may not precisely outline the local immune
      status in the uterus. This survey is a continuation of our previous studies on
      potential usefulness of menstrual blood (MB) immunophenotyping as a tool for
      investigation of immunological disturbances in pregnancy-related disorders.
      Peripheral blood (PB) and MB from healthy fertile (n = 15), unexplained recurrent
      spontaneous abortion (URSA; n = 15), and unexplained infertile women (n = 8) were
      collected simultaneously in the second day of their menstrual cycle and frequency
      of natural killer T (NKT)-like cell subpopulations were assessed by flow
      cytometry. Menstrual blood of all experimental groups contained higher percentage
      of TCRalphabeta+, CD45RO+, and CD16- NKT-like cells compared to corresponding PB.
      Frequency of MB NKT-like cells in unexplained infertile participants was lower
      than fertile and URSA groups. Compared to normal participants, patients with URSA
      had lower frequency of PB TCRalphabeta+ and higher CD16+, while in infertile
      woman frequencies of PB CD45RO+, CD45RO-, CD16-, IL17+, and MB CD45RO+ NKT-like
      cells were lower. Although, PB and MB seemingly have the same histological
      nature, our results showed that MB contained different composition of NKT-like
      subsets with different cytokine profiles and could be viewed as one potential
      biological sample for evaluation of patients with infertility and URSA.

PMID- 29576003
TI  - ISH Newsletter.

PMID- 29576004
TI  - Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic
      Severity Grade in Predicting EVAR Outcomes.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a predictor of poor outcomes for
      patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity
      grade (ASG) represents a quantitative mechanism for assessing anatomical
      suitability for endovascular aortic repair. Anatomic severity grade has been
      correlated with repair outcomes and resource utilization. The purpose of this
      study was to identify a novel renal perfusion metric as a way to assist ASG with
      predicting EVAR outcomes. METHODS: Retrospective review of a prospectively
      maintained database identified elective infrarenal aortic aneurysm repair cases.
      Anatomic grading was undertaken by independent reviewers. Using volumetric
      software, kidney volume, and a novel measure of kidney functional volume, the
      volumetric nephrogram (VN) was recorded. Systematic evaluation of the
      relationship of kidney volume and VN to CKD and ASG was undertaken using linear
      regression and receiver-operator statistical tools. RESULTS: A total of 386 cases
      with patient and anatomic data were identified and graded. Mean age was 72.9 +/-
      0.4 years. Renal volume <281 mL correlated with CKD (area under the curve [AUC] =
      .708; P <= .0001). Volumetric nephrogram <22.5 HU.L correlated with CKD (AUC =
      0.764; P <= .0001). High (>=15) ASG scores correlated with both renal volume (AUC
      = .628; P <= .0001) and VN (AUC = .628; P <= .0001). Regression analysis
      demonstrated a strong, inverse relationship between ASG and VN ( R2 = .95).
      CONCLUSION: These data demonstrate that VN is a strong predictor of CKD in a
      large database of patients undergoing elective aneurysm repair. We demonstrate an
      inverse relationship between renal function and ASG that has not been previously
      described in the literature. Additionally, we have shown that VN complements ASG
      as a model of overall cardiovascular health and atherosclerotic burden. Outcomes
      in patients with poor renal function may be related to anatomical issues in
      addition to well-described systemic ramifications.

PMID- 29576005
TI  - Intravascular Ultrasound-Guided Endovascular Stenting of Renal Vein in Nutcracker
      Syndrome.

PMID- 29576006
TI  - Pretesting With the Injection of Small Doses of Contrast Media Is Dangerous and
      Should Be Omitted.

PMID- 29576007
TI  - The Evaluation of Aortic Diameter Changes During Long-Term Follow-Up After
      Endovascular Treatment of Acute Blunt Traumatic Thoracic Aortic Injuries.
AB  - PURPOSE: To evaluate the variations in aortic diameters and long-term results in
      patients who underwent thoracic endovascular aortic repair (TEVAR) for acute
      blunt traumatic thoracic aortic injuries (BTTAIs). MATERIALS AND METHODS: We
      retrospectively evaluated 23 patients with a mean age of 39 years (range: 17-74
      years) who underwent TEVAR for BTTAI between October 2000 and November 2014. All
      of the patients underwent computed tomography angiography (CTA) before hospital
      discharge as a baseline imaging for the subsequent follow-up examinations. The
      technical success, overall survival, and complications were evaluated.
      Furthermore, the aortic diameters outside of the stent-graft (1 cm proximal and 1
      cm distal to the stent-graft) and the aortic diameters within the stent-graft (2
      cm distal to the proximal end and 2 cm proximal to the distal end) were assessed.
      The diameters at baseline on CTA were compared with those of the latest available
      follow-up examination. RESULTS: Technical success was 100% with a mean follow-up
      of 65.4 months (range: 12-171 months). No death was registered, and 2 (8.7%) of
      23 endograft-related complications (1 stent-graft distal infolding and 1 endoleak
      2 and 4 months after the procedure, respectively) were observed. An increase in
      aortic diameter either proximal or distal to the stent-graft (mean value 0.7 and
      0.5 mm, respectively) or within the stent-graft (mean value of 0.5 mm for both
      proximal and distal diameters) was registered (mean follow-up at 65.4 months,
      range: 12-171 months). CONCLUSION: Aortic dilatation following TEVAR for BTTAI is
      minimal during long-term follow-up. Endovascular treatment represents a durable
      and safe option in acute BTTAIs.

PMID- 29576010
TI  - Geographic origin as a determinant of left ventricular mass and diastolic
      function - the Cardiovascular Risk in Young Finns Study.
AB  - AIMS: Eastern Finns have higher risk of coronary heart disease (CHD) and carotid
      intima-media thickness than western Finns although current differences in CHD
      risk factors are minimal. Left ventricular (LV) mass and diastolic function
      predict future cardiovascular events but their east-west differences are unknown.
      We examined the association of eastern/western baseline origin with LV mass and
      diastolic function. METHODS: The study population included 2045 subjects of the
      Cardiovascular Risk in Young Finns Study with data from the baseline survey
      (1980) and the latest follow-up (2011) when echocardiography was performed at the
      age of 34-49 years. RESULTS: Subjects with eastern baseline origin had in 2011
      higher LV mass (139+/-1.0 vs. 135+/-1.0 g, p=0.006) and E/e'-ratio indicating
      weaker LV diastolic function (4.86+/-0.03 vs. 4.74+/-0.03, p=0.02) than western
      subjects. Results were independent of age, sex, area of examination and CHD risk
      factors such as blood pressure and BMI (LV mass indexed with height: p<0.0001;
      E/e'-ratio: p=0.01). LV end-diastolic volume was higher among subjects with
      eastern baseline origin (135+/-0.9 vs. 131+/-0.9 ml, p=0.0011) but left atrial
      end-systolic volume, also indicating LV diastolic function, was not different
      between eastern and western subjects (43.4+/-0.5 vs. 44.0+/-0.5 ml, p=0.45). Most
      of the subjects were well within the normal limits of these echocardiographic
      measurements. CONCLUSIONS: In our healthy middle-aged population, geographic
      origin in eastern Finland associated with higher LV mass compared to western
      Finland. Higher E/e'-ratio suggests that subjects with eastern baseline origin
      might have higher prevalence of diastolic dysfunction in the future than western
      subjects.

PMID- 29576011
TI  - Temporal trend and regional disparity in osteoarthritis hospitalisations in
      Sweden 1998-2015.
AB  - AIM: This study investigated time trend and regional disparities in
      hospitalisations due to osteoarthritis (OA) among people aged >=20 years in
      Sweden from 1998 through 2015. METHODS: National and regional data on hospital
      admissions with a primary diagnosis of OA were collected from the National
      Patient Register. The absolute and relative regional disparities were assessed
      using the absolute weighted mean difference from overall mean and the index of
      disparity. We applied joinpoint regression for temporal trend analysis of
      hospitalisations and the Mann-Kendall trend test for disparity measures. Changes
      in number of OA hospitalisations between 1998-2000 and 2013-2015 were analysed
      using two counterfactual scenarios. RESULTS: During 1998-2015, OA
      hospitalisations constituted 2.0% of all hospitalisations, with higher
      proportions among women (58.7%) and those aged 70-74 years (18.0%). The age
      standardised rate of OA hospitalisation and its proportions from all and
      musculoskeletal disorders hospitalisations rose, on average, by >2.0% per year
      during the study period. OA hospitalisation rates rose statistically
      significantly in all age groups except for the youngest and oldest age groups.
      The proportion of hip OA from all OA hospitalisations declined, while the
      opposite was observed for knee OA. The relative regional disparities declined in
      men, and the absolute regional disparities rose among women over time. The
      population growth and ageing could explain only about one third of the observed
      increases in the absolute number of OA hospitalisations between 1998-2000 and
      2013-2015. CONCLUSIONS: OA hospitalisations have increased substantially,
      suggesting the need to improve OA prevention and primary-care management in
      Sweden.

PMID- 29576012
TI  - Output-oriented analysis of the wet mechanical processing of polyolefin-rich
      waste for feedstock recycling.
AB  - In recent years, an increasing number of studies have revealed that plastics and
      their components (e.g. plasticisers) pose an environmental risk. However, it is
      hard to imagine how our industrialised society could do without these materials,
      since the fields of application are manifold. One possible approach to tackle
      this mounting problem is the implementation of a comprehensive and well
      functioning collection and recycling system. An international comparison shows
      that only a small proportion of the total plastics in circulation is collected
      and recycled. The investigations conducted under the present research project,
      'Plastic Reborn', focused on both identification and analysis of the discharge
      paths of polyolefin-rich waste streams, under the Austrian waste management
      system. Another objective was determining the utilisation potential of the output
      fractions of these polyolefin-rich waste streams, generated from a wet mechanical
      processing pilot plant. Experiments have shown that the polyolefins are
      successfully separated from the waste streams and that a total polyolefin
      potential of 429,000 t y-1 remains unexploited in the Austrian waste management
      system. Thus, these separated plastic fractions can make a significant
      contribution to the implementation of the European Circular Economy Directive.
      The residual fractions meet the legal and company-specific requirements for their
      use as solid recovered fuels in co-combustion plants.

PMID- 29576013
TI  - Omega-3 fatty acid supplement reduces activation of NADPH oxidase in intracranial
      atherosclerosis stenosis.
AB  - Objectives Intracranial atherosclerotic stenosis (ICAS) is one of the most common
      causes of stroke worldwide. We adapted a rat model of atherosclerosis to study
      brain intracranial atherosclerosis, and further investigated how omega-3 fatty
      acids (O3FA) attenuated the development of ICAS by reducing the generation of
      reactive oxygen species (ROS) and the activation of nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase (NOX) activity. Methods Adult male Sprague
      Dawley rats were divided into control normal-cholesterol or high-cholesterol diet
      groups with or without O3FA for up to 6 weeks. NG-nitro-L-arginine methyl ester
      (L-NAME, 3 mg/mL), a nitric oxide synthase inhibitor, was added to the drinking
      water of the high-cholesterol groups during the first 2 weeks. The rats received
      supplementation with O3FA (5 mg/kg/day) by gavage. At 3 and 6 weeks, we measured
      blood lipid levels, including low-density lipoprotein (LDL), cholesterol (CHO),
      triglycerides (TG), and high-density lipoprotein (HDL) as atherosclerotic blood
      markers. The lumen of middle cerebral artery (MCA) and the thickness of the
      vessel wall were assessed histologically. ROS production was measured. NOX
      activity and mRNA and protein expression of NOX subunits (p47phox, gp91phox,
      p22phox, and p67phox) were measured. Results A high-cholesterol diet exhibited a
      significant increase in the classic blood markers (LDL, CHO, and TG) for
      atherosclerosis, as well as a decrease in HDL. These markers were found to be
      progressively more severe with time. Additionally, increased lumen stenosis and
      intimal thickening were observed in the MCA for this group. Rats given O3FA
      demonstrated attenuation of blood lipid levels with an absence of morphological
      changes.O3FA significantly reduced ROS production and NOX activity in the brain.
      Moreover, O3FA decreased the mRNA and protein expression of the NOX subunits
      p47phox, gp91phox, and p67phox. Conclusions Long-term O3FA dietary
      supplementation prevents the development of intracranial atherosclerosis. This
      O3FA effect appears to be mediated by its attenuation of NOX subunit expression
      and NOX activity, therefore reducing ROS production. O3FA dietary supplement
      shows promising results in the prevention of ICAS.

PMID- 29576014
TI  - Eigen decomposition expedites longitudinal genome-wide association studies for
      milk production traits in Chinese Holstein.
AB  - BACKGROUND: Pseudo-phenotypes, such as 305-day yields, estimated breeding values
      or deregressed proofs, are usually used as response variables for genome-wide
      association studies (GWAS) of milk production traits in dairy cattle.
      Computational inefficiency challenges the direct use of test-day records for
      longitudinal GWAS with large datasets. RESULTS: We propose a rapid longitudinal
      GWAS method that is based on a random regression model. Our method uses Eigen
      decomposition of the phenotypic covariance matrix to rotate the data, thereby
      transforming the complex mixed linear model into weighted least squares analysis.
      We performed a simulation study that showed that our method can control type I
      errors well and has higher power than a longitudinal GWAS method that does not
      include time-varied additive genetic effects. We also applied our method to the
      analysis of milk production traits in the first three parities of 6711 Chinese
      Holstein cows. The analysis for each trait was completed within 1 day with known
      variances. In total, we located 84 significant single nucleotide polymorphisms
      (SNPs) of which 65 were within previously reported quantitative trait loci (QTL)
      regions. CONCLUSIONS: Our rapid method can control type I errors in the analysis
      of longitudinal data and can be applied to other longitudinal traits. We detected
      QTL that were for the most part similar to those reported in a previous study in
      Chinese Holstein. Moreover, six additional SNPs for fat percentage and 13 SNPs
      for protein percentage were identified by our method. These additional 19 SNPs
      could be new candidate quantitative trait nucleotides for milk production traits
      in Chinese Holstein.

PMID- 29576015
TI  - Management of a giant retroperitoneal leiomyoma: a case report.
AB  - BACKGROUND: Leiomyomas are benign tumors observed mainly in adult women. The
      retroperitoneum is a rare location for leiomyomas; almost 100 cases have been
      reported. Because retroperitoneal leiomyomas are paucisymptomatic and the tumor
      size at diagnosis is relatively large, surgical management is challenging.
      Regular follow-up is required because recurrence and malignant sarcomatous
      transformation have been described in a few cases. CASE PRESENTATION: We report a
      case of a 52-year-old North African woman with a 22-cm retroperitoneal leiomyoma.
      A preoperative embolization was performed 2 days before surgery. The clinical,
      therapeutic, and evolutive aspects of this rare entity are discussed.
      CONCLUSIONS: Despite its benignity, retroperitoneal leiomyoma is a challenging
      diagnostic, therapeutic, and evolutive condition. Surgeons must consider mainly
      the tumor's vascularization. Regular follow-up is mandatory because malignant
      transformation cannot be excluded.

PMID- 29576016
TI  - Correction to: Simple motion correction strategy reduces respiratory-induced
      motion artifacts for k-t accelerated and compressed-sensing cardiovascular
      magnetic resonance perfusion imaging.
AB  - Figure 1 of this original publication contained a minor error as one of the lines
      in the "Reconstruction pipline" was not visible. The updated Fig. 1 is published
      in this correction article.

PMID- 29576017
TI  - Diagnostic double strike in the emergency room - two cases of complete pancreatic
      ruptures due to bicycle handlebar injuries on two consecutive days.
AB  - BACKGROUND: Pancreatic injuries are rare in cases of blunt abdominal trauma and
      therefore easily misdiagnosed at time of hospital admission. They are associated
      with a significantly elevated morbidity and lethality. Bicycle handlebar injuries
      are the most common cause of pancreatic trauma in children and adolescents. CASE
      PRESENTATION: We report two cases of a 23-year-old Caucasian woman and a 15-year
      old Caucasian boy who presented to our clinic with a similar history of a bicycle
      accident on 2 consecutive days. Both suffered from a fall from a bicycle with
      bicycle handlebar injury 4 and 6 days prior to admission in our clinic. Emergency
      distal pancreatectomies were performed in both cases. CONCLUSIONS: Pancreatic
      injuries must be highly suspected in bicycle handlebar injuries, even if
      amylase/lipase levels or ultrasound findings seem unremarkable. The best initial
      strategies are early computed tomography and a quick referral to a level 1 trauma
      center. Distal pancreatectomy is the treatment of choice in cases of complete
      rupture of the pancreatic body.

PMID- 29576019
TI  - Denominator Matters in Estimating Antimicrobial Use: A Comparison of Days Present
      and Patient Days.
AB  - Patient days and days present were compared to directly measured person time to
      quantify how choice of different denominator metrics may affect antimicrobial use
      rates. Overall, days present were approximately one-third higher than patient
      days. This difference varied among hospitals and units and was influenced by
      short length of stay.Infect Control Hosp Epidemiol 2018;39:612-615.

PMID- 29576018
TI  - The ctenophore Mnemiopsis leidyi regulates egg production via conspecific
      communication.
AB  - BACKGROUND: Communication between individuals of the same species is an important
      aspect of mating and reproduction in most animals. In simultaneously
      hermaphroditic species with the ability to self-fertilize, communication with
      conspecifics can be essential to avoid inbreeding depression. One such behavioral
      adaptation observed in some simultaneous hermaphrodites is gamete trading. This
      behavior involves individual hermaphrodites in pairs alternating between
      reproducing as the male and female, and, as such, necessarily requires
      communication and coordination between mates. Little is known about communication
      in ctenophores and conspecific communication has not been described in this
      group; however, our previous work suggested that the ctenophore Mnemiopsis leidyi
      might engage in gamete trading. We tested for this possibility by constructing
      divided arenas (both sealed and permeable) that allowed us to measure individual
      egg output for paired M. leidyi. RESULTS: We found that, when not allowed to
      interact, size-matched individuals produced similar numbers of eggs on each side
      of the arena. However, if allowed to interact and exchange water, size-matched
      pairs produce significantly different numbers of eggs on each side of the arena,
      suggesting that these pairs use chemical communication to modulate reproduction
      in the presence of conspecifics as would be expected in gamete trading.
      CONCLUSION: This finding presents exciting new possibilities for future
      investigations into the nature of signaling in M. leidyi. Furthermore, this first
      evidence of conspecific communication in Ctenophora, a group that branched off
      from the rest of animals more than 600 million years ago, has significant
      implications for the signaling ability of the last common ancestor of all
      animals.

PMID- 29576020
TI  - New mastitis phenotypes suitable for genomic selection in meat sheep and their
      genetic relationships with udder conformation and lamb live weights.
AB  - Mastitis can prove expensive in sheep reared for meat production due to costs
      associated with treatment methods, poor lamb growth and premature culling of
      ewes. The most commonly used method to detect mastitis, in dairy systems, is
      somatic cell counts. However, in many meat-producing sheep flocks ewes are not
      routinely handled, thus regular milk sampling is not always possible. It is,
      therefore, worthwhile to investigate alternative phenotypes, such as those
      associated with udder conformation and methods of evaluating somatic cell counts
      in the milk, such as the California Mastitis Test. The main objectives of this
      study were therefore: (a) to estimate genetic parameters of traits relating to
      mastitis and udder conformation in a meat sheep breed; (b) estimate the level of
      association between somatic cell counts and the California Mastitis Test and (c)
      assess the relationships between mastitis and both udder conformation and lamb
      live weights. Data were collected from Texel ewes based on 29 flocks, throughout
      the UK, during 2015 and 2016. The ewes were scored twice each year, at mid- and
      late-lactation. Eight different conformation traits, relating to udder and teat
      characteristics, and milk samples were recorded. The data set comprised of data
      available for 2957 ewes. The pedigree file used contained sire and dam
      information for 31 775 individuals. The animal models used fitted relevant fixed
      and random effects. Heritability estimates for traits relating to mastitis
      (somatic cell score and the California Mastitis Test), ranged from 0.08 to 0.11
      and 0.07 to 0.11, respectively. High genetic correlations were observed between
      somatic cell score and the California Mastitis Test (0.76 to 0.98), indicating
      the California Mastitis Test to be worthwhile for assessing infection levels,
      particularly at mid-lactation. The strongest correlations observed between the
      mastitis traits and the udder conformation traits were associated with udder
      depth (0.61 to 0.75) also at mid-lactation. Negative phenotypic correlations were
      estimated between mastitis and the weight of lamb reared by the ewe (-0.15 to 
      0.23), suggesting that lamb weights fell as infection levels rose. Genetic
      correlations were not significantly different from zero. Reducing mastitis will
      lead to improvements in flock productivity and the health and welfare of the
      animals. It will also improve the efficiency of production and the resilience to
      disease challenge. The economic benefits, therefore, of these results combined
      could be substantial not only in this breed but also in the overall meat sheep
      industry.

PMID- 29576022
TI  - Genetic risk for neuroticism predicts emotional health depending on childhood
      adversity.
AB  - BACKGROUND: Existing evidence for gene * environment interaction (G * E) in
      neuroticism largely relies on candidate gene studies, although neuroticism is
      highly polygenic. This study aimed to investigate the long-term associations
      between polygenic risk scores for neuroticism (PRSN), objective childhood
      adversity and their interplay on emotional health aspects such as neuroticism
      itself, depressive symptoms, anxiety symptoms, loneliness and life satisfaction.
      METHODS: The sample consisted of reared-apart (TRA) and reared-together (TRT)
      middle- and old age twins (N = 699; median age at separation = 2). PRSN were
      created under nine p value cut-off thresholds (p T-s) and the p T with the
      highest degree of neuroticism variance explained was chosen for subsequent
      analyses. Linear regressions were used to assess the associations between PRSN,
      childhood adversity (being reared apart) and emotional health. G * E was further
      investigated using a discordant twin design. RESULTS: PRSN explained up to 1.7%
      (p T < 0.01) of phenotypic neuroticism in the total sample. Analyses across two
      separation groups revealed substantial heterogeneity in the variance explained by
      PRSN; 4.3% was explained in TRT, but almost no effect was observed in TRA.
      Similarly, PRSN explained 4% and 1.7% of the variance in depressive symptoms and
      loneliness, respectively, only in TRT. A significant G * E interaction was
      identified for depressive symptoms. CONCLUSIONS: By taking advantage of a unique
      sample of adopted twins, we demonstrated the presence of G * E in neuroticism and
      emotional health using PRSN and childhood adversity. Our results may indicate
      that genome-wide association studies are detecting genetic main effects
      associated with neuroticism, but not those susceptible to early environmental
      influences.

PMID- 29576021
TI  - Caregiver perceptions of children's linear growth in Bangladesh: a qualitative
      analysis.
AB  - OBJECTIVE: To understand caregivers' perceptions of children's linear growth and
      to identify the cultural meanings and perceptions of risk associated with poor
      height attainment. DESIGN: Three investigators from Bangladesh conducted twelve
      focus group discussions. SETTING: The study was conducted in rural and slum
      settings in Bangladesh. SUBJECTS: Participants included mothers and alternative
      caregivers (n 81) who were recruited by household screening. No eligible,
      recruited subjects refused participation. RESULTS: Caregivers reported limited
      experience with growth monitoring services from the health system. Caregivers
      mainly use visual cues and developmental milestones to understand if children are
      growing properly, and recognize that children normally experience both weight
      gain and linear growth with age. Mothers expressed concern over children's
      malnutrition and short stature, but did not discuss children's failure to attain
      a 'growth potential' or distinguish inherited short stature from stunting.
      Caregivers interpret the consequences of poor height attainment as primarily
      social and economic and cite few health risks. CONCLUSIONS: Linear growth
      interpretation is determined more by community norms than by guidance from
      nutrition programming or the health system. Interventions to prevent or reduce
      linear growth failure may be perceived to have limited value where appropriate
      linear growth in children is determined by comparison to peers and siblings. Such
      perceptions may be significant barriers to programmes addressing stunting
      prevention in settings where many children are stunted. Efforts to raise
      awareness about the risks of linear growth faltering may need to consider
      delivering messages to caregivers that emphasize the social and economic
      consequences of stunting.

PMID- 29576023
TI  - A successful Charter challenge to medicare? Policy options for Canadian
      provincial governments.
AB  - In September 2016, a case went to trial in British Columbia that seeks to test
      the constitutionality of provincial laws that (1) ban private health insurance
      for medically necessary hospital and physician services; (2) ban extra-billing
      (physicians cannot charge patients more than the public tariff); and (3) require
      physicians to work solely for the public system or 'opt-out' and practice
      privately. All provinces have similar laws that have been passed to meet the
      requirements of federal legislation, the Canada Health Act (and thus qualify for
      federal funds). Consequently, a finding of unconstitutionality of one or more of
      these laws could have a very significant impact on the future of Canada's single
      payer system ('medicare'). However, should the court find that a particular law
      is not in compliance with the Canadian Charter of Rights and Freedoms, the baton
      is then passed back to the government which may respond with other laws or
      policies that they believe to be constitutionally compliant. The ultimate impact
      of any successful Charter challenge to laws protecting medicare from
      privatization will thus significantly depend on how Canadian governments respond.
      Provincial governments could allow privatization to undercut equity and access,
      or they could respond creatively with new legal and policy solutions to both
      improve equity and access and tackle some of the problems that have long
      bedeviled Canadian medicare. This paper provides an understanding - grounded in
      comparative health systems evidence - of law and policy options available to
      Canadian lawmakers for limiting two-tier care in the wake of any successful
      challenge to existing laws. The paper presents the results of a large inter
      disciplinary, comparative study, started in 2015, that systematically reviewed
      the legal and broader regulatory schemes used to regulate the public/private
      divide in 15 Organization for Economic Co-Operation and Development countries
      with a particular eye to what the effect of such regulations would be upon wait
      times.

PMID- 29576024
TI  - Source of bias in sugar-sweetened beverage research: a systematic review.
AB  - OBJECTIVE: Financial conflicts of interest involving the food industry have been
      reported to bias nutrition studies. However, some have hypothesized that
      independently funded studies may be biased if the authors have strong a priori
      beliefs about the healthfulness of a food product ('white hat bias'). The extent
      to which each source of bias may affect the scientific literature has not been
      examined. We aimed to explore this question with research involving sugar
      sweetened beverages (SSB) as a test case, focusing on a period during which
      scientific consensus about the adverse health effects of SSB emerged from
      uncertainty. DESIGN: PubMed search of worldwide literature was used to identify
      articles related to SSB and health risks published between 2001 and 2013.
      Financial relationships and article conclusions were classified by independent
      groups of co-investigators. Associations were explored by Fischer's exact tests
      and regression analyses, controlling for covariates. RESULTS: A total of 133
      articles published in English met inclusion criteria. The proportion of industry
      related scientific studies decreased significantly with time, from approximately
      30 % at the beginning of the study period to <5 % towards the end (P=0.003). A
      'strong' or 'qualified' scientific conclusion was reached in 82 % of independent
      v. 7 % of industry-related SSB studies (P<0.001). Industry-related studies were
      overwhelmingly more likely to reach 'weak/null' conclusions compared with
      independent studies regarding the adverse effects of SSB consumption on health
      (OR=57.30, 95 % CI 7.12, 461.56). CONCLUSION: Industry-related research during a
      critical period appears biased to underestimate the adverse health effects of
      SSB, potentially delaying corrective public health action.

PMID- 29576025
TI  - When health technology assessment is confidential and experts have no power: the
      case of Hungary.
AB  - Health technology assessment (HTA) is not simply a mechanistic technical exercise
      as it takes place within a specific institutional context. Yet, we know little
      about how this context influences the operation of HTA and its ability to
      influence policy and practice. We seek to demonstrate the importance of
      considering institutional context, using a case study of Hungary, a country that
      has pioneered HTA in Central and Eastern Europe. We conducted 26 in-depth, semi
      structured interviews with public- and private-sector stakeholders. We found that
      while the HTA Department, the Hungarian HTA organisation, fulfilled its formal
      role envisaged in the legislation, its potential for supporting evidence-based
      decision-making was not fully realised given the low levels of transparency and
      stakeholder engagement. Further, the Department's practical influence throughout
      the reimbursement process was perceived as being constrained by the payer and
      policy-makers, as well as its own limited organisational capacity. There was also
      scepticism as to whether the current operational form of the HTA process
      delivered 'good value for money'. Nevertheless, it still had a positive impact on
      the development of a broader institutional HTA infrastructure in Hungary. Our
      findings highlight the importance of considering institutional context in
      analysing the HTA function within health systems.

PMID- 29576026
TI  - Developmental trends of hot and cool executive function in school-aged children
      with and without autism spectrum disorder: Links with theory of mind.
AB  - The development of executive function (EF) in autism spectrum disorder (ASD) has
      been investigated using only "cool"-cognitive EF tasks while there is limited
      knowledge regarding the development of "hot"-affective EF. Although cool EF
      development and its links to theory of mind (ToM) have been widely examined,
      understanding of the influence of hot EF to ToM mechanisms is minimal. The
      present study introduced a longitudinal design to examine the developmental
      changes in cool and hot EF of children with ASD (n = 45) and matched (to age and
      IQ) controls (n = 37) as well as the impact of EF on ToM development over a
      school year. For children with ASD, although selective cool (working memory and
      inhibition) and hot (affective decision making) EF domains presented age-related
      improvements, they never reached the performance level of the control group.
      Early cool working memory predicted later ToM in both groups but early hot delay
      discounting predicted later ToM only in the ASD group. No evidence was found for
      the reverse pattern (early ToM predicting later EF). These findings suggest that
      improvements in some EF aspects are evident in school age in ASD and highlight
      the crucial role that both cool and hot EF play in ToM development.

PMID- 29576027
TI  - Automatic food detection in egocentric images using artificial intelligence
      technology.
AB  - OBJECTIVE: To develop an artificial intelligence (AI)-based algorithm which can
      automatically detect food items from images acquired by an egocentric wearable
      camera for dietary assessment. DESIGN: To study human diet and lifestyle, large
      sets of egocentric images were acquired using a wearable device, called eButton,
      from free-living individuals. Three thousand nine hundred images containing real
      world activities, which formed eButton data set 1, were manually selected from
      thirty subjects. eButton data set 2 contained 29 515 images acquired from a
      research participant in a week-long unrestricted recording. They included both
      food- and non-food-related real-life activities, such as dining at both home and
      restaurants, cooking, shopping, gardening, housekeeping chores, taking classes,
      gym exercise, etc. All images in these data sets were classified as food/non-food
      images based on their tags generated by a convolutional neural network. RESULTS:
      A cross data-set test was conducted on eButton data set 1. The overall accuracy
      of food detection was 91.5 and 86.4 %, respectively, when one-half of data set 1
      was used for training and the other half for testing. For eButton data set 2,
      74.0 % sensitivity and 87.0 % specificity were obtained if both 'food' and
      'drink' were considered as food images. Alternatively, if only 'food' items were
      considered, the sensitivity and specificity reached 85.0 and 85.8 %,
      respectively. CONCLUSIONS: The AI technology can automatically detect foods from
      low-quality, wearable camera-acquired real-world egocentric images with
      reasonable accuracy, reducing both the burden of data processing and privacy
      concerns.

PMID- 29576028
TI  - Anomalous Brain Development Is Evident in Preschoolers With Attention
      Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a common
      neurological disorder with symptom onset early in childhood. Growing evidence
      suggests anomalous brain development across multiple brain regions is evident in
      school-aged children; however, few studies have examined whether such differences
      are notable in the preschool years when symptom onset typically occurs. METHODS:
      High resolution anatomical (MPRAGE) images and cognitive and behavioral measures
      were analyzed in a total of 90 medication-naive preschoolers, ages 4-5 years (52
      with ADHD, 38 controls; 64.4% boys). RESULTS: Results revealed reductions in
      bilateral frontal, parietal, and temporal lobe gray matter volumes in children
      with ADHD relative to typically developing children, with largest effect sizes
      noted for right frontal and left temporal lobe volumes. Examining frontal lobe
      sub-regions, the largest between group effect sizes were evident for left
      orbitofrontal cortex, left primary motor cortex (M1), and left supplementary
      motor complex (SMC). ADHD-related reductions in specific sub-regions (left
      prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were
      significantly correlated with symptom severity, such that higher ratings of
      hyperactive/impulsive symptoms were associated with reduced cortical volumes.
      CONCLUSIONS: These findings represent the first comprehensive examination of
      cortical volume in preschool children with ADHD, providing evidence that
      anomalous brain structure in ADHD is evident very early in development.
      Furthermore, findings set the stage for developing our understanding of the way
      in which developmental trajectories of anomalous brain development are associated
      with the unfolding of symptoms in childhood ADHD. (JINS, 2018, 24, 531-539).

PMID- 29576030
TI  - Meanings of encounters for close relatives of people with a long-term illness
      within a primary healthcare setting.
AB  - BACKGROUND: Encounters play an important role in the relationship between
      healthcare personnel and the close relatives of people with a long-term
      illness.AimThe aim of this study was to elucidate the meanings of encounters for
      close relatives of people with a long-term illness within a primary healthcare
      setting. METHODS: Interviews using a narrative approach were conducted with seven
      women and three men, and the phenomenological hermeneutic method was used to
      interpret the interview texts. RESULTS: The structural analysis revealed three
      major themes: being confirmed as a family, being informed of the care, and being
      respected as a valuable person. Close relatives stated that they wanted to be
      confirmed as a family and have a familiar and trusting relationship with
      healthcare personnel. They valued being informed concerning the care of the ill
      person so that they could give support at home. It was also important to be
      compassionately viewed as an important person in a welcoming atmosphere based on
      respect and dignity.

PMID- 29576029
TI  - A review of guidance on fish consumption in pregnancy: is it fit for purpose?
AB  - OBJECTIVE: Public health messages to reduce Hg exposure for pregnant women have
      focused exclusively on advice on fish consumption to limit Hg exposure, with
      little account being taken of the positive contribution of fish to nutritional
      quality. The aim of the present review was to compare and contrast the content
      and presentation of national guidelines on fish consumption in pregnancy, and
      comment on their evidence base and impact on consumption. DESIGN: We searched for
      national and international guidelines on fish consumption in pregnancy using
      Internet search strategies. The detailed content and style of presentation of the
      guidelines were compared. The evidence base for the guidelines, and evidence for
      the impact of the guidelines on fish consumption levels, were assessed. RESULTS:
      We identified nineteen national guidelines and three international guidelines.
      There was great variation in the content, complexity and presentation style. The
      guidelines were based largely on the Hg content of fish with far less
      consideration being given to the positive beneficial effects of nutrients
      provided by fish. The complexity of the guidelines may lead to pregnant women
      reducing their fish intake, or not eating fish at all. CONCLUSIONS: Guidelines on
      fish consumption in pregnancy should take the beneficial effects of fish into
      account. Guidelines need to be clear and memorable, and appropriately
      disseminated, to achieve impact. Guidelines could include visual rather than
      narrative content. Use of technology, for example apps, could enable women to
      record their fish consumption in real time and log compliance with guidance over
      a week or other time period.

PMID- 29576032
TI  - Letter to the Editor: Cumulative trauma as a potential explanation for the
      elevated risk of suicide associated with psychotic experiences: commentary on
      Moriyama et al. 'The association between psychotic experiences and traumatic life
      events'.

PMID- 29576031
TI  - Reducing meat consumption in the USA: a nationally representative survey of
      attitudes and behaviours.
AB  - OBJECTIVE: Excess meat consumption, particularly of red and processed meats, is
      associated with nutritional and environmental health harms. While only a small
      portion of the population is vegetarian, surveys suggest many Americans may be
      reducing their meat consumption. To inform education campaigns, more information
      is needed about attitudes, perceptions, behaviours and foods eaten in meatless
      meals. DESIGN: A web-based survey administered in April 2015 assessed meat
      reduction behaviours, attitudes, what respondents ate in meatless meals and
      sociodemographic characteristics. SETTING: Nationally representative, web-based
      survey in the USA. SUBJECTS: US adults (n 1112) selected from GfK Knowledgeworks'
      50 000-member online panel. Survey weights were used to assure
      representativeness. RESULTS: Two-thirds reported reducing meat consumption in at
      least one category over three years, with reductions of red and processed meat
      most frequent. The most common reasons for reduction were cost and health;
      environment and animal welfare lagged. Non-meat reducers commonly agreed with
      statements suggesting that meat was healthy and 'belonged' in the diet.
      Vegetables were most often consumed 'always' in meatless meals, but cheese/dairy
      was also common. Reported meat reduction was most common among those aged 45-59
      years and among those with lower incomes. CONCLUSIONS: The public and
      environmental health benefits of reducing meat consumption create a need for
      campaigns to raise awareness and contribute to motivation for change. These
      findings provide rich information to guide intervention development, both for the
      USA and other high-income countries that consume meat in high quantities.

PMID- 29576033
TI  - Child neglect and its relation to emotional and behavioral problems: A cross
      sectional study of primary school-aged children in Tanzania.
AB  - Child maltreatment is known to engender negative emotional and behavioral
      consequences. Although neglect is the most frequent form of maltreatment, it has
      thus far only received little attention, especially when looking at low-resource
      countries. The current study investigated possible associations between neglect
      and internalizing and externalizing problems. As neglect and abuse often co
      occur, the latter was controlled for. In total, 409 Tanzanian primary school
      students (52% boys, M = 10.5 years, range = 6-15) participated in the cross
      sectional study. Structured clinical interviews were conducted assessing
      maltreatment, internalizing problems, and externalizing problems. Overall, 31% (n
      = 128) of the children reported at least one type of physical neglect and 31% (n
      = 127) of emotional neglect. Using structural equation modeling, we found a
      significant association between neglect and internalizing (beta = 0.59, p < .01)
      and externalizing problems (beta = 0.35, p < .05). However, these associations
      could only be detected in younger children (ages 6-9), whereas in older children
      (ages 10-15), mental health problems were significantly related to violence and
      abuse. Our findings suggest that the current age may influence the association
      between maltreatment type and the development of internalizing and/or
      externalizing problems.

PMID- 29576034
TI  - Science and self-assessment: phrenological charts 1840-1940.
AB  - This paper looks at phrenological charts as mediators of (pseudo-)scientific
      knowledge to individual clients who used them as a means of self-assessment.
      Phrenologists propagated the idea that the human mind could be categorized into
      different mental faculties, with each particular faculty represented in a
      different area of the brain and by bumps on the head. In the US and the UK
      popular phrenologists examined individual clients for a fee. Drawing on a
      collection of phrenological charts completed for individual clients, this paper
      shows how charts aspired to convey new ideals of selfhood by using the authority
      of science in tailor-made certificates, and by teaching clients some of the basic
      practices of that science. Hitherto historians studying phrenology have focused
      mainly on the attraction of the content of phrenological knowledge for the wider
      public, but in this paper I show how the charts enabled clients to participate
      actively in creating knowledge of their own bodies and selves.

PMID- 29576035
TI  - Cortisol, cortisone, and BDNF in amniotic fluid in the second trimester of
      pregnancy: Effect of early life and current maternal stress and socioeconomic
      status.
AB  - The prenatal environment shapes the offspring's phenotype; moreover,
      transgenerational stress and stress during pregnancy may play a role. Brain
      derived neurotrophic factor (BDNF) and glucocorticoids influence neurodevelopment
      during pregnancy, and there is evidence that BDNF in amniotic fluid is mainly of
      fetal origin, while the source of glucocorticoids is maternal. We tested the
      hypothesis that maternal early life stress, psychiatric diagnoses, anxiety,
      perceived stress, and socioeconomic status influence BDNF and glucocorticoid
      concentrations in amniotic fluid in the second trimester. We studied 79 pregnant
      women who underwent amniocentesis in the early second trimester and analyzed
      BDNF, cortisol, and cortisone concentrations in amniotic fluid. The endocrine
      data were related to maternal early life adversities (Childhood Trauma
      Questionaire), perceived stress (Perceived Stress Scale), anxiety, socioeconomic
      status (family income), and the presence of psychiatric diseases. We found BDNF
      in amniotic fluid to be positively related to maternal early adversity (Childhood
      Trauma Questionaire). Low family income (socioeconomic status) was related to
      high amniotic fluid glucocorticoid concentrations. Neither glucocorticoid
      concentrations nor hydroxy steroid dehydrogenase (HSD2) activity could be related
      to BDNF concentrations in amniotic fluid. Early maternal adverse events may be
      reflected in the fetal BDNF regulation, and it should be tested whether this
      relates to differences in neurodevelopment.

PMID- 29576036
TI  - Introducing a family intervention to elderly with first episode psychosis.
AB  - Schizophrenia guidelines list family interventions as an efficient means in
      reducing relapses. Interventions aim to help families cope with their relative's
      problems more effectively, provide support and education, and reduce levels of
      distress and improve the family communication (see deHaan et al., 2002).

PMID- 29576037
TI  - The Mediating Role of Coping between Competitive Anxiety and Sport Commitment in
      Adolescent Athletes.
AB  - Framed in cognitive-motivational-relational theory of emotions (Lazarus, 1999),
      this study aimed to test how coping mediated the relationship between competitive
      anxiety and sport commitment in a sample of adolescent athletes. Five-hundred
      adolescents (M = 16.42; SD = 1.54) participated in our study. Participants
      completed competitive anxiety, coping, and sport commitment measures. We defined
      the measurement model using confirmatory factor analysis and exploratory
      structural equation modeling; and compared two different models of mediation
      (i.e., total and partial mediation) using structural equation modeling. Results
      favored partial mediation model where cognitive anxiety factors predicted sport
      commitment. Results from this model suggest direct and mediated structural
      relations between concepts. Somatic anxiety had a weak influence on sport
      commitment (total effects = 0.090 [-.131, .311]). Worry showed a positive
      influence on sport commitment (total effects = .375 [.262, .486]) through direct
      and mediated effects. Concentration disruption showed a negative impact on sport
      commitment (total effects = -.544 [-.724, -.363]) trough mediated effects only,
      showing a negative path on task-oriented coping and a positive path on
      disengagement-oriented coping. As a whole, our findings identify task coping
      efforts undertaken by adolescent athletes as a key element in the relationship
      between competitive anxiety and sport commitment. These findings provide
      preliminary evidence for the design of coping interventions in adolescents.

PMID- 29576038
TI  - Predictors of Suicide Behavior Relapse in Pediatric Population.
AB  - Identifying patients at increased risk of suicide remains a challenge today. It
      has been reported that 10% of patients committing a suicide attempt end up dying
      and that both the risk and the severity of clinical symptomatology increase with
      the number of attempts. Within the framework of selective and indicated
      prevention, it is essential to identify the group of patients with an increased
      risk of recurrence. The objective of this study is to identify factors predicting
      suicide attempt relapse to improve the decision making process in the therapeutic
      approach to suicidal behavior. The methodology employed was a longitudinal design
      aimed at identifying factors, in a binary logistic regression model (stepwise),
      predicting the repetition of suicidal behavior among a sample of 417 participants
      aged between 8 and 17 years old, at the six months follow-up. A statistically
      significant model chi2(3, N = 417) = 18.610; p < .001; Nagelkerke R 2 = .096
      including the following factors was obtained: current diagnosis of personality
      disorder/maladaptive personality OR = .806, p = .028, 95% CI [1.091, 4.595],
      personal history of self-injury OR = .728, p = .043, 95% CI [1.023, 4.192], and
      family history of psychopathological diagnosis OR = .925, p = .021, 95% CI
      [1.151, 5.530]. Considering these results, having a diagnosis of personality
      disorder or maladaptive personality traits, presence or history of self-harm and
      family history of psychopathology draws a predictive profile of autolytic attempt
      recurrence during the six months after the initial intervention at the emergency
      room.

PMID- 29576039
TI  - Performance, health and physiological responses of newly weaned feedlot cattle
      supplemented with feed-grade antibiotics or alternative feed ingredients.
AB  - With increased regulations regarding the use of feed-grade antimicrobials in
      livestock systems, alternative strategies to enhance growth and immunity of
      feedlot cattle are warranted. Hence, this experiment compared performance, health
      and physiological responses of cattle supplemented with feed-grade antibiotics or
      alternative feed ingredients during the initial 60 days in the feedlot.
      Angus*Hereford calves (63 steers+42 heifers) originating from two cow-calf
      ranches were weaned on day -3, obtained from an auction yard on day -2 and road
      transported (800 km; 12 h) to the feedlot. Upon arrival on day -1, shrunk BW was
      recorded. On day 0, calves were ranked by sex, source and shrunk BW, and
      allocated to one of 21 pens. Pens were assigned to receive (7 pens/treatment) a
      free-choice total mixed ration containing: (1) lasalocid (360 mg/calf daily of
      Bovatec; Zoetis, Florham Park, NJ, USA)+chlortetracycline (350 mg/calf of
      Aureomycin at cycles of 5-day inclusion and 2-day removal from diet; Zoetis) from
      days 0 to 32, and monensin only (360 mg/calf daily of Rumensin; Elanco Animal
      Health, Greenfield, IN, USA) from days 33 to 60 (PC), (2) sodium saccharin-based
      sweetener (Sucram at 0.04 g/kg of diet dry matter; Pancosma SA; Geneva,
      Switzerland)+plant extracts containing eugenol, cinnamaldehyde and capsicum (800
      mg/calf daily of XTRACT Ruminants 7065; Pancosma SA) from days 0 to 32 and XTRACT
      only (800 mg/calf daily) from days 33 to 60 (EG) or (3) no supplemental
      ingredients (CON; days 0 to 60). Calves were assessed for bovine respiratory
      disease (BRD) signs and dry matter intake was recorded from each pen daily.
      Calves were vaccinated against BRD pathogens on days 0 and 22. Shrunk BW was
      recorded on day 61, and blood samples collected on days 0, 6, 11, 22, 33, 43 and
      60. Calf ADG was greater (P=0.04) in PC v. EG and tended (P=0.09) to be greater
      in PC v. CON. Feed efficiency also tended (P=0.09) to be greater in PC v. CON,
      although main treatment effect for this response was not significant (P=0.23).
      Mean serum titers against bovine respiratory syncytial virus were greater in EG
      v. PC (P=0.04) and CON (tendency; P=0.08). Collectively, the inclusion of
      alternative feed ingredients prevented the decrease in feed efficiency when
      chlortetracycline and ionophores were not added to the initial feedlot diet, and
      improved antibody response to vaccination against the bovine respiratory
      syncytial virus in newly weaned cattle.

PMID- 29576040
TI  - Genome-wide identification of runs of homozygosity islands and associated genes
      in local dairy cattle breeds.
AB  - Runs of homozygosity (ROH) are widely used as predictors of whole-genome
      inbreeding levels in cattle. They identify regions that have an unfavorable
      effect on a phenotype when homozygous, but also identify the genes associated
      with traits of economic interest present in these regions. Here, the distribution
      of ROH islands and enriched genes within these regions in four dairy cattle
      breeds were investigated. Cinisara (71), Modicana (72), Reggiana (168) and
      Italian Holstein (96) individuals were genotyped using the 50K v2 Illumina
      BeadChip. The genomic regions most commonly associated with ROHs were identified
      by selecting the top 1% of the single nucleotide polymorphisms (SNPs) most
      commonly observed in the ROH of each breed. In total, 11 genomic regions were
      identified in Cinisara and Italian Holstein, and eight in Modicana and Reggiana,
      indicating an increased ROH frequency level. Generally, ROH islands differed
      between breeds. The most homozygous region (>45% of individuals with ROH) was
      found in Modicana on chromosome 6 within a quantitative trail locus affecting
      milk fat and protein concentrations. We identified between 126 and 347 genes
      within ROH islands, which are involved in multiple signaling and signal
      transduction pathways in a wide variety of biological processes. The gene
      ontology enrichment provided information on possible molecular functions,
      biological processes and cellular components under selection related to milk
      production, reproduction, immune response and resistance/susceptibility to
      infection and diseases. Thus, scanning the genome for ROH could be an alternative
      strategy to detect genomic regions and genes related to important economic
      traits.

PMID- 29576041
TI  - The prevalence of depression in general hospital inpatients: a systematic review
      and meta-analysis of interview-based studies.
AB  - BACKGROUND: Comorbid depression in the medically ill is clinically important.
      Admission to a general hospital offers an opportunity to identify and initiate
      treatment for depression. However, we first need to know how common depression is
      in general hospital inpatients. We aimed to address this question by
      systematically reviewing the relevant literature. METHODS: We reviewed published
      prevalence studies in any language which had used diagnostic interviews of
      general hospital inpatients and met basic methodological quality criteria. We
      focussed on interview-based studies in order to estimate the proportion of
      patients with a diagnosis of depressive illness. RESULTS: Of 158 relevant
      articles, 65 (41%) describing 60 separate studies met our inclusion criteria. The
      31 studies that focussed on general medical and surgical inpatients reported
      prevalence estimates ranging from 5% to 34%. There was substantial, highly
      statistically significant, heterogeneity between studies which was not materially
      explained by the covariates we were able to consider. The average of the reported
      prevalences was 12% (95% CI 10-15), with a 95% prediction interval of 4-32%. The
      remaining 29 studies, of a variety of specific clinical populations, are
      described. CONCLUSIONS: The available evidence suggests a likely prevalence high
      enough to make it worthwhile screening hospital inpatients for depression and
      initiating treatment where appropriate. Further, higher quality, research is
      needed to clarify the prevalence of depression in specific settings and to
      further explore the reasons for the observed heterogeneity in estimates.

PMID- 29576042
TI  - A Generalizable, Data-Driven Approach to Predict Daily Risk of Clostridium
      difficile Infection at Two Large Academic Health Centers.
AB  - OBJECTIVE An estimated 293,300 healthcare-associated cases of Clostridium
      difficile infection (CDI) occur annually in the United States. To date, research
      has focused on developing risk prediction models for CDI that work well across
      institutions. However, this one-size-fits-all approach ignores important hospital
      specific factors. We focus on a generalizable method for building facility
      specific models. We demonstrate the applicability of the approach using
      electronic health records (EHR) from the University of Michigan Hospitals (UM)
      and the Massachusetts General Hospital (MGH). METHODS We utilized EHR data from
      191,014 adult admissions to UM and 65,718 adult admissions to MGH. We extracted
      patient demographics, admission details, patient history, and daily
      hospitalization details, resulting in 4,836 features from patients at UM and
      1,837 from patients at MGH. We used L2 regularized logistic regression to learn
      the models, and we measured the discriminative performance of the models on held
      out data from each hospital. RESULTS Using the UM and MGH test data, the models
      achieved area under the receiver operating characteristic curve (AUROC) values of
      0.82 (95% confidence interval [CI], 0.80-0.84) and 0.75 ( 95% CI, 0.73-0.78),
      respectively. Some predictive factors were shared between the 2 models, but many
      of the top predictive factors differed between facilities. CONCLUSION A data
      driven approach to building models for estimating daily patient risk for CDI was
      used to build institution-specific models at 2 large hospitals with different
      patient populations and EHR systems. In contrast to traditional approaches that
      focus on developing models that apply across hospitals, our generalizable
      approach yields risk-stratification models tailored to an institution. These
      hospital-specific models allow for earlier and more accurate identification of
      high-risk patients and better targeting of infection prevention strategies.
      Infect Control Hosp Epidemiol 2018;39:425-433.

PMID- 29576043
TI  - Antimicrobial Stewardship and Infection Prevention-Leveraging the Synergy: A
      Position Paper Update.

PMID- 29576044
TI  - HealthNavigator: a mobile application for chronic disease screening and linkage
      to services at an urban Primary Health Network.
AB  - Mobile applications (apps) are promising tools to support chronic disease
      screening and linkage to health services. They have the potential to increase
      healthcare access for vulnerable populations. The HealthNavigator app was
      developed to provide chronic disease risk assessments, linkage to local general
      practitioners (GPs) and lifestyle programs, and a personalised health report for
      discussion with a GP. Assessments were either self-administered or facilitated by
      community health workers through a Primary Health Network (PHN) initiative
      targeting ethnically diverse communities. In total, 1492 assessments (80.4% self
      administered, 19.6% facilitated) were conducted over a 12-month period in
      Queensland, Australia. Of these, 26% of people screened came from postcodes
      representing the lowest quartile of socioeconomic disadvantage. When compared
      against self-administered assessments, subjects screened by the facilitated
      program were more likely to be born outside Australia (80.5 v. 33.2%, P<0.001),
      and to fall within a high risk category based on cardiovascular risk scores (19.8
      v. 13.7%, P<0.01) and type 2 diabetes mellitus risk scores (58.0 v. 40.1%,
      P<0.001). Mobile apps embedded into PHN programs may be a useful adjunct for the
      implementation of community screening programs. Further research is needed to
      determine their effect on health service access and health outcomes.

PMID- 29576045
TI  - Current perspectives of CASA applications in diverse mammalian spermatozoa.
AB  - Since the advent of computer-aided sperm analysis (CASA) some four decades ago,
      advances in computer technology and software algorithms have helped establish it
      as a research and diagnostic instrument for the analysis of spermatozoa. Despite
      mammalian spermatozoa being the most diverse cell type known, CASA is a great
      tool that has the capacity to provide rapid, reliable and objective quantitative
      assessment of sperm quality. This paper provides contemporary research findings
      illustrating the scientific and commercial applications of CASA and its ability
      to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic
      mammals, wildlife species) at both structural and functional levels. The
      potential of CASA to quantitatively measure essential aspects related to sperm
      subpopulations, hyperactivation, morphology and morphometry is also demonstrated.
      Furthermore, applications of CASA are provided for improved mammalian sperm
      quality assessment, evaluation of sperm functionality and the effect of different
      chemical substances or pathologies on sperm fertilising ability. It is clear that
      CASA has evolved significantly and is currently superior to many manual
      techniques in the research and clinical setting.

PMID- 29576046
TI  - Editorial overview: Cancer genomics: RNA metabolism and translation in cancer
      pathogenesis and therapy.

PMID- 29576049
TI  - Tattooing in prison: a risk factor for HCV infection among inmates in the
      Quebec's provincial correctional system.
AB  - PURPOSE: To determine the prevalence of hepatitis C virus (HCV) and identify
      related risk factors among inmates in Quebec provincial prisons. METHODS:
      Anonymous cross-sectional data were collected between May 2014 and March 2015 for
      1315 men and 250 women who completed a questionnaire and provided oral fluid
      samples. RESULTS: The global prevalence of HCV infection was 11.9% in male
      participants and 19.2% in female participants (P = .003). Among people who inject
      drugs (PWID), the prevalence was much higher compared to that in persons who does
      not: 51.0% versus 2.4% in men (P < .001) and 61.4% versus 2.8% in women (P <
      .001). In the multivariable analysis, lifetime history of injection drug use was
      the most important risk factor for HCV infection (adjusted odds ratio [AOR]:
      14.2; 95% confidence interval [95% CI]: 9.5-21.4), with needle sharing
      significantly associated with HCV among PWID (AOR: 1.4; 95% CI: 1.1-1.7).
      Tattooing in prison was frequent, especially among men (37.2%), and independently
      associated with HCV infection among non-PWID (AOR: 2.8; 95% CI: 1.4-5.6).
      CONCLUSION: Inmates are at high risk for HCV infection especially because of a
      high proportion of active or past PWID among them. In addition, tattooing while
      in prison seems to contribute to HCV infection among non-PWID.

PMID- 29576050
TI  - Illustrating a "consequential" shift in the study of health inequalities: a
      decomposition of racial differences in the distribution of body mass.
AB  - PURPOSE: We present a conceptual introduction to "distributional inequalities"
      differences in distributions of risk factors or other outcomes between social
      groups-as a consequential shift for research on health inequalities. We also
      review a companion analytical methodology, "distributional decomposition", which
      can assess the population characteristics that explain distributional
      inequalities. METHODS: Using the 1999-2012 U.S. National Health and Nutrition
      Examination Survey, we apply statistical decomposition to (a) document gender
      specific, black-white inequalities in the distribution of body mass index (BMI)
      and, (b) assess the extent to which demographic (age), socioeconomic (family
      income, education), and behavioral predictors (caloric intake, physical activity,
      smoking, alcohol consumption) are associated with broader distributional
      inequalities in BMI. RESULTS: Black people demonstrate favorable or no different
      caloric intake, smoking, or alcohol consumption than whites, but worse levels of
      physical activity. Racial inequalities extend beyond the obesity threshold to the
      broader BMI distribution. Demographic, socioeconomic, and behavioral
      characteristics jointly explain more of the distributional inequality among men
      than women. CONCLUSIONS: Black-white distributional inequalities are present both
      among men and women, although the mechanisms may differ by gender. The notion of
      "distributional inequalities" offers an additional purchase for studying social
      inequalities in health.

PMID- 29576051
TI  - Editorial note.

PMID- 29576052
TI  - Norisoboldine, a natural aryl hydrocarbon receptor agonist, alleviates TNBS
      induced colitis in mice, by inhibiting the activation of NLRP3 inflammasome.
AB  - Although the etiology of inflammatory bowel disease is still uncertain,
      increasing evidence indicates that the excessive activation of NLRP3 inflammasome
      plays a major role. Norisoboldine (NOR), an alkaloid isolated from Radix
      Linderae, has previously been demonstrated to inhibit inflammation and IL-1beta
      production. The present study was to examine the effect of NOR on colitis and the
      underlying mechanism related to NLRP3 inflammasome activation. Our results showed
      that NOR alleviated colitis symptom in mice induced by 2, 4, 6-trinitrobenzene
      sulfonic acid (TNBS). Moreover, it significantly reduced expressions of cleaved
      IL-1beta, NLRP3 and cleaved Caspase-1 but not ASC in colons of mice. In THP-1
      cells, NOR suppressed the expressions of NLRP3, cleaved Caspase-1 and cleaved IL
      1beta but not ASC induced by lipopolysaccharide (LPS) and adenosine triphosphate
      (ATP). Furthermore, NOR could activate aryl hydrocarbon receptor (AhR) in THP-1
      cells, inducing CYP1A1 mRNA expression, and promoting dissociation of AhR/HSP90
      complexes, association of AhR and ARNT, AhR nuclear translocation, XRE reporter
      activity and binding activity of AhR/ARNT/XRE. Both siAhR and alpha
      naphthoflavone (alpha-NF) markedly diminished the inhibition of NOR on NLRP3
      inflammasome activation. In addition, NOR elevated Nrf2 level and reduced ROS
      level in LPS- and ATP-stimulated THP-1 cells, which was reversed by either siAhR
      or alpha-NF treatment. Finally, correlations between activation of AhR and
      attenuation of colitis, inhibition of NLRP3 inflammasome activation and up
      regulation of Nrf2 level in colons were validated in mice with TNBS-induced
      colitis. Taken together, NOR ameliorated TNBS-induced colitis in mice through
      inhibiting NLRP3 inflammasome activation via regulating AhR/Nrf2/ROS signaling
      pathway.

PMID- 29576053
TI  - Qualitative detection of ginsenosides in brain tissues after oral administration
      of high-purity ginseng total saponins by using polyclonal antibody against
      ginsenosides.
AB  - Given the limited studies and conflicting findings, the transport character of
      ginsenosides crossing the blood-brain barrier (BBB) remains unclear. The present
      study was designed to qualitatively determine the distribution of ginsenosides in
      brain tissues after oral administration of ginseng total saponins, using high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined
      with immunohistochemistry. In brain tissue homogenates, ginsenoside Rg1 was
      detectable and no other ginsenosides or their metabolites were found. No
      ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining
      of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed
      the localization of ginsenosides in brain tissues. Furthermore,
      immunofluorescence double staining revealed that ginsenosides widely existed in
      vascular endotheliocytes and astrocytes, and in few neurons. These results
      indicated that Rg1 was the main component that entered the brain after oral
      administration of ginseng total saponins and that ginsenosides could cross the
      BBB, although the transport capability of ginsenosides through the BBB may be
      poor.

PMID- 29576054
TI  - Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by
      protecting the blood brain barrier through MMP-9 inhibition and anti
      inflammation.
AB  - Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia
      Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the
      treatment of cerebrovascular diseases for centuries. The present study aimed to
      determine the brain protective effects of SAA against cerebral ischemia
      reperfusion injury in rats, and to figure out whether SAA could protect the blood
      brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal
      cerebral ischemia reperfusion model was induced by middle cerebral artery
      occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered
      intravenously at doses of 5, 10, and 20 mg.kg-1. SAA significantly reduced the
      infarct volumes and neurological deficit scores. Immunohistochemical analyses
      showed that SAA treatments could also improve the morphology of neurons in
      hippocampus CA1 and CA3 regions and increase the number of neurons. Western
      blotting analyses showed that SAA downregulated the levels of MMP-9 and
      upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to
      attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced
      degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral
      NF-kappaB p65 activation and reduced inflammation response. Our results suggested
      that SAA could be a promising agent to attenuate cerebral ischemia reperfusion
      injury through MMP-9 inhibition and anti-inflammation activities.

PMID- 29576055
TI  - Buyang Huanwu Decoction ameliorates ischemic stroke by modulating multiple
      targets with multiple components: In vitro evidences.
AB  - Buyang Huanwu Decoction (BYHWD) is a well-known traditional Chinese medicine
      prescription which is used to treat ischaemic stroke and stroke-induced
      disabilities. However, the exact mechanism underlying BYHWD's amelioration of
      ischaemic stroke and its effective constituents remain unclear. The present study
      aimed to identify the effective constituents of BYHWD and to further explore its
      action mechanisms in the amelioration of ischaemic stroke by testing the
      activities of 15 absorbable chemical constituents of BYHWD with the same methods
      under the same conditions. The following actions of these 15 compounds were
      revealed: 1) Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-beta-D
      glucoside, paeonol, calycosin-7-O-beta-D-glucoside, astraisoflavan-7-O-beta-D
      glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin
      A (Con A)-induced T lymphocyte proliferation; 2) Propyl gallate, calycosin-7-O
      beta-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced
      apoptosis in RAW264.7 cells; 3) Propyl gallate and formononetin significantly
      inhibited LPS-induced NO release; 4) Hydroxysafflor yellow A and inosine
      protected PC12 cells against the injuries caused by glutamate; and 5)
      Formononetin, astragaloside IV, astraisoflavan-7-O-beta-D-glucoside, inosine,
      paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid
      significantly suppressed the constriction of the thoracic aorta induced by KCl in
      rats. In conclusion, the results from the present study suggest that BYHWD exerts
      its ischaemic stroke ameliorating activities by modulating multiple targets with
      multiple components.

PMID- 29576056
TI  - Brazilin and Caesalpinia sappan L. extract protect epidermal keratinocytes from
      oxidative stress by inducing the expression of GPX7.
AB  - Caesalpinia sappan L., belonging to the family Leguminosae, is a medicinal plant
      that is distributed in Southeast Asia. The dried heartwood of this plant is used
      as a traditional ingredient of food, red dyes, and folk medicines in the
      treatment of diarrhea, dysentery, tuberculosis, skin infections, and
      inflammation. Brazilin is the major active compound, which has exhibited various
      pharmacological effects, including anti-platelet activity, anti-hepatotoxicity,
      induction of immunological tolerance, and anti-inflammatory and antioxidant
      activities. The present study aimed to evaluate the antioxidant activity and
      expression of antioxidant enzymes of C. sappan L. extract and its major compound,
      brazilin, in human epidermal keratinocytes exposed to UVA irradiation. Our
      results indicated that C. sappan L. extract reduced UVA-induced H2O2 production
      via GPX7 activation. Moreover, brazilin exhibited antioxidant effects that were
      similar to those of C. sappan L. via glutathione peroxidase 7 (GPX7), suggesting
      that C. sappan L. extract and its natural compound represent potential treatments
      for oxidative stress-induced photoaging of skin.

PMID- 29576057
TI  - Construction of a mutant of Actinoplanes sp. N902-109 that produces a new
      rapamycin analog.
AB  - In the present study, we introduced point mutations into Ac_rapA which encodes a
      polyketide synthase responsible for rapamycin biosynthesis in Actinoplanes sp.
      N902-109, in order to construct a mutant with an inactivated enoylreductase (ER)
      domain, which was able to synthesize a new rapamycin analog. Based on the
      homologous recombination induced by double-strand breaks in chromosome mediated
      by endonuclease I-SceI, the site-directed mutation in the first ER domain of
      Ac_rapA was introduced using non-replicating plasmid pLYERIA combined with an I
      SceI expression plasmid. Three amino acid residues of the active center, Ala-Gly
      Gly, were converted to Ala-Ser-Pro. The broth of the mutant strain SIPI-027 was
      analyzed by HPLC and a new peak with the similar UV spectrum to that of rapamycin
      was found. The sample of the new peak was prepared by solvent extraction, column
      chromatography, and crystallization methods. The structure of new compound, named
      as SIPI-rapxin, was elucidated by determining and analyzing its MS and NMR
      spectra and its biological activity was assessed using mixed lymphocyte reaction
      (MLR). An ER domain-deficient mutant of Actinoplanes sp. N902-109, named as SIPI
      027, was constructed, which produced a novel rapamycin analog SIPI-rapxin and its
      structure was elucidated to be 35, 36-didehydro-27-O-demethylrapamycin. The
      biological activity of SIPI-rapxin was better than that of rapamycin. In
      conclusion, inactivation of the first ER domain of rapA, one of the modular
      polyketide synthase responsible for macro-lactone synthesis of rapamycin, gave
      rise to a mutant capable of producing a novel rapamycin analog, 35, 36-didehydro
      27-O-demethylrapamycin, demonstrating that the enoylreductase domain was
      responsible for the reduction of the double bond between C-35 and C-36 during
      rapamycin synthesis.

PMID- 29576058
TI  - Antioxidant xanthones and anthraquinones isolated from a marine-derived fungus
      Aspergillus versicolor.
AB  - Chemical examination of an EtOAc extract of cultured Aspergillus versicolor
      fungus from deep-sea sediments resulted in the isolation of four xanthones, eight
      anthraquinones and five alkaloids, including a new xanthone, oxisterigmatocystin
      D (1) and a new alkaloid, aspergillusine A (13). High resolution electron impact
      mass spectrometry (HR-EI-MS), FT-IR spectroscopy, and NMR techniques were used to
      elucidate the structures of these compounds, and the absolute configuration of
      compound 1 was established by its NMR features and coupling constant.
      Furthermore, the biosynthesis pathway of these xanthones and anthraquinones were
      deduced, and their antioxidant activity and cytotoxicity in human cancer cell
      lines (HTC-8, Bel-7420, BGC-823, A549, and A2780) were evaluated. The trolox
      equivalent antioxidant capacity (TEAC) assay indicated most of the xanthones and
      anthraquinones possessing moderate antioxidant activities. The Nrf2-dependent
      luciferase reporter gene assay revealed that compounds 6, 7, 9, and 12
      potentially activated the expression of Nrf2-regulated gene. In addition,
      compounds 5 and 11 showed weak cytotoxicity on A549 with the IC50 values of 25.97
      and 25.60 MUmol.L-1, respectively.

PMID- 29576059
TI  - Sedative and antinociceptive activities of two new sesquiterpenes isolated from
      Ricinus communis.
AB  - Two new sesquiterpenes, trivially named ricinusoids A (1) and ricinusoids B (2),
      were isolated from ethyl acetate fraction of Ricinus communis. The structures of
      new compounds were elucidated by detailed spectroscopic techniques, including 1D-
      and 2D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds (1-2) were
      also assessed for in-vivo sedative and analgesic like effects in open field and
      acetic acid induced writhing tests respectively at 5, 10, and 20 mg.kg-1 i.p.
      Pretreatment of both test compounds caused significant (P <= 0.05) reduction in
      locomotive activity like sedative agents and abdominal constrictions like
      analgesics. Both compounds (1-2) possessed marked sedative and antinociceptive
      effects in animal models.

PMID- 29576060
TI  - Discovery of novel limonin derivatives as potent anti-inflammatory and analgesic
      agents.
AB  - Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized
      by adding various tertiary amines onto the C (7)-position of limonin. The
      synthesized compounds possessed favorable physicochemical property, and the
      intrinsic solubility of the novel compounds were significantly improved, compared
      with limonin. Different pharmacological models were used to evaluate the
      analgesic and anti-inflammatory activities of the target compounds. Compound V-A
      8 exhibited the strongest in vivo activity among the novel limonin analogs; its
      analgesic activity was more potent than aspirin and its anti-inflammatory
      activity was stronger than naproxen under our testing conditions.

PMID- 29576061
TI  - Corrigendum to "A strategy for promoting astaxanthin accumulation in
      Haematococcus pluvialis by 1-aminocyclopropane-1-carboxylic acid application"
      [Journal of Biotechnology Vol. 236./Iss 20. (2016) 120-127.].

PMID- 29576062
TI  - Phytic acid transport in Phaseolus vulgaris: A new low phytic acid mutant in the
      PvMRP1 gene and study of the PvMRPs promoters in two different plant systems.
AB  - Phytic acid (InsP6) is the main storage form of phosphate in seeds. In the plant
      it plays an important role in response to environmental stress and hormonal
      changes. InsP6 is a strong chelator of cations, reducing the bioavailability of
      essential minerals in the diet. Only a common bean low phytic acid (lpa1) mutant,
      affected in the PvMRP1 gene, coding for a putative tonoplastic phytic acid
      transporter, was described so far. This mutant is devoid of negative pleiotropic
      effects normally characterising lpa mutants. With the aim of isolating new common
      bean lpa mutants, an ethyl methane sulfonate mutagenized population was screened,
      resulting in the identification of an additional lpa1 allele. Other putative lpa
      lines were also isolated. The PvMRP2 gene is probably able to complement the
      phenotype of mutants affected in the PvMRP1 gene in tissues other than the seed.
      Only the PvMRP1 gene is expressed at appreciable levels in cotyledons.
      Arabidopsis thaliana and Medicago truncatula transgenic plants harbouring 1.5 kb
      portions of the intergenic 5' sequences of both PvMRP genes, fused upstream of
      the GUS reporter, were generated. GUS activity in different organs suggests a
      refined, species-specific mechanisms of regulation of gene expression for these
      two PvMRP genes.

PMID- 29576063
TI  - Review on the significance of chlorine for crop yield and quality.
AB  - The chloride concentration in the plant determines yield and quality formation
      for two reasons. First, chlorine is a mineral nutrient and deficiencies thereof
      induce metabolic problems that interfere with growth. However, due to low
      requirement of most crops, deficiency of chloride hardly appears in the field.
      Second, excess of chloride, an event that occurs under chloride-salinity, results
      in severe physiological dysfunctions impairing both quality and yield formation.
      The chloride ion can effect quality of plant-based products by conferring a salty
      taste that decreases market appeal of e.g. fruit juices and beverages. However,
      most of the quality impairments are based on physiological dysfunctions that
      arise under conditions of chloride-toxicity: Shelf life of persimmon is shortened
      due to an autocatalytic ethylene production in fruit tissues. High concentrations
      of chloride in the soil can increase phyto-availability of the heavy metal
      cadmium, accumulating in wheat grains above dietary intake thresholds. When crops
      are cultivated on soils that are moderately salinized by chloride, nitrate
      fertilization might be a strategy to suppress uptake of chloride by means of an
      antagonistic anion-anion uptake competition. Overall, knowledge about proteins
      that catalyse chloride-efflux out of the roots or that restrict xylem loading is
      needed to engineer more resistant crops.

PMID- 29576064
TI  - A comparison between genotyping-by-sequencing and array-based scoring of SNPs for
      genomic prediction accuracy in winter wheat.
AB  - The utilization of DNA molecular markers in plant breeding to maximize selection
      response via marker-assisted selection (MAS) and genomic selection (GS) has
      revolutionized plant breeding. A key factor affecting GS applicability is the
      choice of molecular marker platform. Genotyping-by-sequencing scored SNPs (GBS
      scored SNPs) provides a large number of markers, albeit with high rates of
      missing data. Array scored SNPs are of high quality, but the cost per sample is
      substantially higher. The objectives of this study were 1) compare GBS-scored
      SNPs, and array scored SNPs for genomic selection applications, and 2) compare
      estimates of genomic kinship and population structure calculated using the two
      marker platforms. SNPs were compared in a diversity panel consisting of 299 hard
      winter wheat (Triticum aestivum L.) accessions that were part of a multi-year,
      multi-environments association mapping study. The panel was phenotyped in Ithaca,
      Nebraska for heading date, plant height, days to physiological maturity and grain
      yield in 2012 and 2013. The panel was genotyped using GBS-scored SNPs, and array
      scored SNPs. Results indicate that GBS-scored SNPs is comparable to or better
      than Array-scored SNPs for genomic prediction application. Both platforms
      identified the same genetic patterns in the panel where 90% of the lines were
      classified to common genetic groups. Overall, we concluded that GBS-scored SNPs
      have the potential to be the marker platform of choice for genetic diversity and
      genomic selection in winter wheat.

PMID- 29576065
TI  - Facilitated citrate-dependent iron translocation increases rice endosperm iron
      and zinc concentrations.
AB  - Iron deficiency affects one third of the world population. Most iron
      biofortification strategies have focused on genes involved in iron uptake and
      storage but facilitating internal long-distance iron translocation has been
      understudied for increasing grain iron concentrations. Citrate is a primary iron
      chelator, and the transporter FERRIC REDUCTASE DEFECTIVE 3 (FRD3) loads citrate
      into the xylem. We have expressed AtFRD3 in combination with AtNAS1
      (NICOTIANAMINE SYNTHASE 1) and PvFER (FERRITIN) or with PvFER alone to facilitate
      long-distance iron transport together with efficient iron uptake and storage in
      the rice endosperm. The citrate and iron concentrations in the xylem sap of
      transgenic plants increased two-fold compared to control plants. Iron and zinc
      levels increased significantly in polished and unpolished rice grains to more
      than 70% of the recommended estimated average requirement (EAR) for iron and 140%
      of the recommended EAR for zinc in polished rice grains. Furthermore, the
      transformed lines showed normal phenotypic growth, were tolerant to iron
      deficiency and aluminum toxicity, and had grain cadmium levels similar to control
      plants. Together, our results demonstrate that deploying FRD for iron
      biofortification has no obvious anti-nutritive effects and should be considered
      as an effective strategy for reducing human iron deficiency anemia.

PMID- 29576066
TI  - OsERF71 confers drought tolerance via modulating ABA signaling and proline
      biosynthesis.
AB  - Plants have evolved multiple protective strategies to adapt to adverse
      environmental conditions. Upland rice (UR) has evolved as a "drought-resistant
      type". However, little is known about genes or mechanisms in UR that underlying
      drought tolerance at the molecular level. Here we report isolation and functional
      characterization of the ERF gene, OsERF71, from the UR variety, IRAT109. The
      expression of OsERF71 was induced by abscisic acid (ABA) and various abiotic
      stresses preferentially in IRAT109 under ABA, dehydration, and polyethyleneglycol
      (PEG) treatments. OsERF71 was verified as a nuclear-localized protein and had
      transcriptional activity in yeast cells. Overexpression of the OsERF71 in
      Nipponbare demonstrated a significant increase in tolerance to drought stress and
      a reduced rate of water loss. In contrast, OsERF71 interference lines were
      sensitive to drought stress and exhibited a higher rate of water loss. OsERF71
      overexpressing lines also showed enhanced tolerance to high salinity. Moreover,
      OsERF71 regulated the expression of several ABA- responsive and proline
      biosynthesis genes under drought stress, resulting in enhanced sensitivity to
      exogenous ABA treatment and proline accumulation. Accordingly, we suggest that
      OsERF71 plays a positive role in drought stress tolerance by increasing the
      expression of genes associated with ABA signaling and proline biosynthesis under
      stress.

PMID- 29576067
TI  - ShCIGT, a Trihelix family gene, mediates cold and drought tolerance by
      interacting with SnRK1 in tomato.
AB  - Abiotic stress, such as drought and cold stress, have a major impact on plant
      growth and development. The trihelix transcription factor family plays important
      roles in plant morphological development and adaptation to abiotic stresses. In
      this study, we isolated a cold-induced gene named ShCIGT from the wild tomato
      species Solanum habrochaites and found that it contributes to abiotic stress
      tolerance. ShCIGT belongs to the GT-1 subfamily of the trihelix transcription
      factors. It was constitutively expressed in various tissues. Its expression was
      induced by multiple abiotic stresses and abscisic acid (ABA). Overexpression of
      ShCIGT in cultivated tomato enhanced cold and drought stress tolerance. In
      addition, the transgenic plants displayed a reduced sensitivity to ABA during
      post-germination growth. We found that ShCIGT interacts with SnRK1, an energy
      sensor in the metabolic signaling network, which controls plant metabolism,
      growth and development, and stress tolerance. Based on these data, we conclude
      ShCIGT may improve abiotic-stress tolerance in tomato by interacting with SnRK1.

PMID- 29576068
TI  - Control of Aspergillus flavus growth and aflatoxin production in transgenic maize
      kernels expressing a tachyplesin-derived synthetic peptide, AGM182.
AB  - Aspergillus flavus is an opportunistic, saprophytic fungus that infects maize and
      other fatty acid-rich food and feed crops and produces toxic and carcinogenic
      secondary metabolites known as aflatoxins. Contamination of maize with aflatoxin
      poses a serious threat to human health in addition to reducing the crop value
      leading to a substantial economic loss. Here we report designing a tachyplesin1
      derived synthetic peptide AGM182 and testing its antifungal activity both in
      vitro and in planta. In vitro studies showed a five-fold increase in antifungal
      activity of AGM182 (vs. tachyplesin1) against A. flavus. Transgenic maize plants
      expressing AGM182 under maize Ubiquitin-1 promoter were produced through
      Agrobacterium-mediated transformation. PCR products confirmed integration of the
      AGM182 gene, while RT-PCR of maize RNA confirmed the presence of AGM182
      transcripts. Maize kernel screening assay using a highly aflatoxigenic A. flavus
      strain (AF70) showed up to 72% reduction in fungal growth in the transgenic
      AGM182 seeds compared to isogenic negative control seeds. Reduced fungal growth
      in the AGM182 transgenic seeds resulted in a significant reduction in aflatoxin
      levels (76-98%). The results presented here show the power of computational and
      synthetic biology to rationally design and synthesize an antimicrobial peptide
      against A. flavus that is effective in reducing fungal growth and aflatoxin
      contamination in an economically important food and feed crop such as maize.

PMID- 29576069
TI  - Effects of GhWUS from upland cotton (Gossypium hirsutum L.) on somatic
      embryogenesis and shoot regeneration.
AB  - The WUSCHEL (WUS) gene encodes a plant-specific homeodomain-containing
      transcriptional regulator, which plays important roles during embryogenesis, as
      well as in the formation of shoot and flower meristems. Here, we isolated two
      homologues of Arabidopsis thaliana WUS (AtWUS), GhWUS1a_At and GhWUS1b_At, from
      upland cotton (Gossypium hirsutum). Domain analysis suggested that the two
      putative GhWUS proteins contained a highly conserved DNA-binding HOX domain and a
      WUS-box. Expression profile analysis showed that GhWUSs were predominantly
      expressed during the embryoid stage. Ectopic expression of GhWUSs in Arabidopsis
      could induce somatic embryo and shoot formation from seedling root tips.
      Furthermore, in the absence of exogenous hormone, overexpression of GhWUSs in
      Arabidopsis could promote shoot regeneration from excised roots, and in the
      presence of exogenous auxin, excised roots expressing GhWUS could be induced to
      produce somatic embryo. In addition, expression of the chimeric GhWUS repressor
      in cotton callus inhibited embryogenic callus formation. Our results show that
      GhWUS is an important regulator of somatic embryogenesis and shoot regeneration.

PMID- 29576070
TI  - Reactive oxygen species triggering systemic programmed cell death process via
      elevation of nuclear calcium ion level in tomatoes resisting tobacco mosaic
      virus.
AB  - Programmed cell death (PCD) plays a positive role in the systemic response of
      plants to pathogen resistance. It has been confirmed that local tobacco mosaic
      virus (TMV) infecting tomato leaves can induce systemic PCD process in root-tip
      tissues. But up to now the underlying physiological mechanisms are poorly
      understood. This study focused on the detailed investigation of the physiological
      responses of root-tip cells during the initiation of systemic PCD. Physiological,
      biochemical examination and cytological observation showed that 1 day post
      inoculation (dpi) of TMV inoculation there was an increase in calcium
      fluorescence intensity in root tip tissue cells. Then at 2 dpi, 4 dpi, 8 dpi and
      15 dpi, the fluorescence intensity of calcium ion continued to increase. However,
      at 5 dpi, the reactive oxygen species (ROS) began to accumulate in the root-tip
      cells. And finally at 20 dpi, the obvious PCD reaction was detected. In addition,
      the experimental results also showed that the above process involved the
      elevation of two types of intracellular Ca2+, including cytoplasmic calcium
      ([Ca2+]cyt) and nuclear calcium ([Ca2+]nuc). The [Ca2+]cyt, as a pilot signal
      could lead to the subsequent elevation of intracellular ROS concentration. Then,
      the high levels of ROS stimulated an increase of [Ca2+]nuc and eventually caused
      PCD reactions in the root-tip tissues. In particular, the high level of nuclear
      calcium is an essential mediator in systemic PCD of plants.

PMID- 29576071
TI  - Boron deficiency inhibits root growth by controlling meristem activity under
      cytokinin regulation.
AB  - Significant advances have been made in the last years trying to identify
      regulatory pathways that control plant responses to boron (B) deficiency. Still,
      there is a lack of a deep understanding of how they act regulating growth and
      development under B limiting conditions. Here, we analyzed the impact of B
      deficit on cell division leading to root apical meristem (RAM) disorganization.
      Our results reveal that inhibition of cell proliferation under the regulatory
      control of cytokinins (CKs) is an early event contributing to root growth arrest
      under B deficiency. An early recovery of QC46:GUS expression after transferring B
      deficient seedlings to control conditions revealed a role of B in the maintenance
      of QC identity whose loss under deficiency occurred at later stages of the
      stress. Additionally, the D-type cyclin CYCD3 overexpressor and triple mutant
      cycd3;1-3 were used to evaluate the effect on mitosis inhibition at the G1-S
      boundary. Overall, this study supports the hypothesis that meristem activity is
      inhibited by B deficiency at early stages of the stress as it does cell
      elongation. Likewise, distinct regulatory mechanisms seem to take place depending
      on the severity of the stress. The results presented here are key to better
      understand early signaling responses under B deficiency.

PMID- 29576072
TI  - Strigolactones affect the translocation of nitrogen in rice.
AB  - Strigolactones (SLs) are involved in the nutrient-dependent control of plant root
      and shoot architecture. The total sufficient uptake of nitrogen (N), and also its
      appropriate distribution, is essential for the normal growth and development of
      plants; however, the effect of SLs on N translocation in plants remains unknown.
      Here, the SL-signaling mutant dwarf 3 (d3), the biosynthesis mutant dwarf 10
      (d10), and wild-type (WT) rice (Oryza sativa ssp. Japonica cv. Nipponbare) were
      used to investigate the relationship between N nutrition and the regulatory role
      of SLs. Relative to WT, the d10 mutant had a higher N concentration in older
      leaves but a lower N concentration in younger leaves, while the d3 mutant showed
      a considerably lower N concentration, especially in its younger leaves under
      normal N levels. By contrast, both d3 and d10 mutants contained higher N in their
      leaves under N-deficient conditions. The 15N uptake and distribution analysis
      revealed that the significantly different N concentrations among the d3, d10, and
      WT plants only occurred in their leaves, not in their roots. Moreover, when
      provided with an external supply of GR24, the synthetic SLs altered the leaf N
      distribution of the d10 mutant but not those of the d3 mutant and WT. Together,
      these results suggested that the effect of SLs on plant growth and development
      may be linked to N translocation to different shoot tissues.

PMID- 29576073
TI  - Unraveling the transcriptional complexity of compactness in sistan grape cluster.
AB  - Yaghooti grape of Sistan is the earliest ripening grape in Iran, harvested every
      May annually. It is adapted to dry conditions in Sistan region and its water
      requirement is less than the other grape cultivars. The transcriptional
      complexity of this grape was studied in three stages of cluster development.
      Totally, 24121 genes were expressed in different cluster development steps (step
      1: cluster formation, step 2: berry formation, step 3: final size of cluster) of
      which 3040 genes in the first stage, 2381 genes in the second stage and 2400
      genes in the third stage showed a significant increase in expression. GO analysis
      showed that when the clusters are ripening, the activity of the nucleus,
      cytoplasmic, cytosol, membrane and chloroplast genes in the cluster architecture
      cells decreases. In contrast, the activity of the endoplasmic reticulum, vacuole
      and extracellular region genes enhances. When Yaghooti grape is growing and
      developing, some of metabolic pathways were activated in the response to biotic
      and abiotic stresses. Gene co-expression network reconstruction showed that
      AGAMOUS is a key gene in compactness of Sistan grape cluster, because it
      influences on expression of GA gene which leads to increase cluster length and
      berries size.

PMID- 29576075
TI  - Ectopic expression of StCBF1and ScCBF1 have different functions in response to
      freezing and drought stresses in Arabidopsis.
AB  - Solanum tuberosum potato species constitute the bulk of economically and
      agronomically important potato production. However, S. tuberosum is a drought-
      and frost-sensitive species that is incapable of acclimating to the cold. Solanum
      commersonii is a tuber-bearing wild potato species that exhibits greater frost
      and drought resistance than S. tuberosum. CBF/DREB (C-REPET BINDING
      FACTOR/DROUGHT RESPONSE ELEMENT BINGING FACTOR) transcription factors play
      important roles in response to a variety of abiotic stresses, such as cold,
      drought and salt stresses. To explore different functions between S. tuberosum
      CBF1 (StCBF1) and S. commersonii CBF1 (ScCBF1), Arabidopsis was transformed with
      the ScCBF1 and StCBF1 genes driven by a constitutive CaMV35S promoter. Our
      results reveal that the ScCBF1 transgenic lines are much more tolerant to
      freezing and drought than the StCBF1 transgenic lines. The development of
      transgenic plants was altered, resulting in dwarf phenotype with delayed
      flowering and thicker and additional rosette leaves. The expression levels of
      several COR (COLD-RESPONSIVE) genes and development-related genes, including
      genes that inhibited plant growth (GA2ox7, RGL3) and delayed flowering (FLC) were
      higher in transgenic plants. These results suggest that these two potato CBF1
      play important roles in the plant response to abiotic stress and can influence
      plant growth and development, and ScCBF1 plays a more pronounced function than
      StCBF1.

PMID- 29576074
TI  - CsMYB5a and CsMYB5e from Camellia sinensis differentially regulate anthocyanin
      and proanthocyanidin biosynthesis.
AB  - Tea is one of the most widely consumed nonalcoholic beverages worldwide.
      Polyphenols are nutritional compounds present in the leaves of tea plants.
      Although numerous genes are functionally characterized to encode enzymes that
      catalyze the formation of diverse polyphenolic metabolites, transcriptional
      regulation of those different pathways such as late steps of the proanthcoyanidin
      (PA) pathway remains unclear. In this study, using different tea transcriptome
      databases, we screened at least 140 R2R3-MYB transcription factors (TFs) and
      grouped them according to the basic function domains of the R2R3 MYB TF
      superfamily. Among 140 R2R3 TFs, CsMYB5a and CsMYB5e were chosen for analysis
      because they may be involved in PA biosynthesis regulation. CsMYB5a
      overexpressing tobacco plants exhibited downregulated anthocyanin accumulation
      but a high polymeric PA content in the flowers. Overexpression of CsMYB5e in
      tobacco plants did not change the anthocyanin content but increased the
      dimethylaminocinnamaldehyde-stained PA content. RNA-seq and qRT-PCR analyses
      revealed that genes related to PA and anthocyanin biosynthesis pathways were
      markedly upregulated in both CsMYB5a- and CsMYB5e-overexpressing flowers. Three
      UGTs and four GSTs were identified as involved in PA and anthocyanin
      glycosylation and transportation in transgenic plants. These results provide new
      insights into the regulation of PA and anthocyanin biosynthesis in Camellia
      sinensis.

PMID- 29576076
TI  - GmHMA3 sequesters Cd to the root endoplasmic reticulum to limit translocation to
      the stems in soybean.
AB  - A single point-mutation in GmHMA3 (Glycine max heavy metal-associated ATPase; a
      wild type allele cloned from a low Cd-accumulated soybean) is closely associated
      with seed cadmium (Cd) concentration. It is linked to Cd transportation in yeast,
      and is primarily expressed in the roots of plants. We hypothesized that the
      function of GmHMA3w in soybean would be akin to that of OsHMA3 in rice, which
      expresses in the root tonoplast and sequestrates Cd into the root vacuole to
      reduce Cd translocation to the shoots and limit its accumulation in the seeds. In
      this study, the transient expression of the GmHMA3w-GFP fusion protein in rice
      mesophyll protoplasts indicated that the subcellular localization of GmHAM3w was
      in the endoplasmic reticulum (ER). Overexpression of GmHMA3w increased the Cd
      concentration in the roots, decreased the Cd concentration in the stems, and did
      not affect the Cd concentration in the leaves. Additionally, its overexpression
      did not alter the Cd concentration across the whole plant. These findings
      indicated that GmHMA3w does not influence the Cd uptake, but limits the
      translocation of Cd from the roots to the stems. GmHMA3w thus acts in metal
      transportation. Assessment of the subcellular distribution of Cd indicated that
      GmHMA3w facilitated transport of Cd from the cell wall fraction to the organelle
      fraction, and then sequestrated Cd into the root ER, thus limiting its
      translocation to the stems. Additionally, the results also suggested that the ER
      constitutes a site of particularly high Cd sensitively in plants.

PMID- 29576077
TI  - CYSTATHIONINE GAMMA-SYNTHASE activity in rice is developmentally regulated and
      strongly correlated with sulfate.
AB  - An important goal of rice cultivar development is improvement of protein quality,
      especially with respect to essential amino acids such as methionine. With the
      goal of increasing seed methionine content, we generated Oryza sativa ssp.
      japonica cv. Taipei 309 transgenic lines expressing a feedback-desensitized
      CYSTATHIONINE GAMMA-SYNTHASE from Arabidopsis thaliana (AtD-CGS) under the
      control of the maize ubiquitin promoter. Despite persistently elevated
      cystathionine gamma-synthase (CGS) activity in the AtD-CGS transgenic lines
      relative to untransformed Taipei, sulfate was the only sulfur-containing compound
      found to be elevated throughout vegetative development. Accumulation of
      methionine and other sulfur-containing metabolites was limited to the leaves of
      young plants. Sulfate concentration was found to strongly and positively
      correlate with CGS activity across vegetative development, irrespective of
      whether the activity was provided by the endogenous rice CGS or by a combination
      of endogenous and AtD-CGS. Conversely, the concentrations of glutathione, valine,
      and leucine were clearly negatively correlated with CGS activity in the same
      tissues. We also observed a strong decrease in CGS activity in both untransformed
      Taipei and the AtD-CGS transgenic lines as the plants approached heading stage.
      The mechanism for this downregulation is currently unknown and of potential
      importance for efforts to increase methionine content in rice.

PMID- 29576078
TI  - Wheat expansin gene TaEXPA2 is involved in conferring plant tolerance to Cd
      toxicity.
AB  - Cadmium (Cd) is a severe and toxic heavy metal pollutant that affects plant
      growth and development. In this study, we found that the expression of an
      expansin gene, TaEXPA2, was upregulated in wheat leaves under CdCl2 toxicity. We
      characterized the involvement of TaEXPA2 in conferring Cd tolerance. Tobacco
      plants overexpressing TaEXPA2 showed higher germination rate, root elongation,
      and biomass accumulation compared to the wild-type (WT) plants upon CdCl2
      treatment. The improved photosynthetic parameters and lesser cellular damage in
      transgenic plants exposed to Cd compared to that in the WT plants suggest that
      TaEXPA2 overexpression improves Cd tolerance in plants. Furthermore, we noticed
      that Cd was efficiently effluxed out of the cytoplasm in the transgenic plants
      owing to the enhanced activities of H+-ATPase, V-ATPase, and PPase, which helped
      in conferring Cd tolerance. Moreover, Cd concentration and ROS accumulation were
      lower in the transgenic plants than in WT plants as a consequence of enhanced
      antioxidant enzyme activities in the former. In addition, atexpa2, an Arabidopsis
      mutant, exhibited lower biomass and shorter primary root compared to its WT under
      Cd toxicity; however, the phenotype was recovered upon expression of TaEXPA2 in
      these mutants. Our results demonstrate that TaEXPA2 confers tolerance to Cd
      toxicity. The changed absorption/transportation of Cd and the antioxidative
      capacity may be involved in the improved tolerance of the transgenic plants with
      overexpression of TaEXPA2 to CdCl2 toxicity.

PMID- 29576079
TI  - Genome-wide identification and expression analysis of chitinase gene family in
      Brassica rapa reveals its role in clubroot resistance.
AB  - Chitinases, a category of pathogenesis-related proteins, are responsible for
      catalyzing the hydrolysis of chitin into the N-acetyl-d-glucosamine. Therefore,
      chitinases are believed to function as a guardian against chitin-containing
      pathogens. Here, we examined the role of the Brassica rapa chitinase family genes
      in clubroot disease. A total of 33 chitinase genes were identified and grouped
      into five classes based on their conserved domain. They were distributed unevenly
      across eight chromosomes in B. rapa, and 31 of them contained few introns (<=2).
      In addition, the expression of these genes was organ-specific, and 14 genes were
      expressed differentially in response to Plasmodiophora brassicae challenge of
      clubroot-susceptible (CS NIL) and resistant (CR NIL) lines. Furthermore, reduced
      pathogen DNA content and clubroot symptoms were observed in the CS NILs after
      their treatment with chitin oligosaccharides 24 h prior to inoculation with P.
      brassicae. The findings indicate that chitinases play a crucial role in pathogen
      resistance of the host plants. The results offer an insight into the role of
      chitinase in B. rapa-P. brassicae interaction.

PMID- 29576080
TI  - Seasonal nitrogen cycling in temperate trees: Transport and regulatory mechanisms
      are key missing links.
AB  - Nutrient accumulation, one of the major ecosystem services provided by forests,
      is largely due to the accumulation and retention of nutrients in trees. This
      review focuses on seasonal cycling of nitrogen (N), often the most limiting
      nutrient in terrestrial ecosystems. When leaves are shed during autumn, much of
      the N may be resorbed and stored in the stem over winter, and then used for new
      stem and leaf growth in spring. A framework exists for understanding the
      metabolism and transport of N in leaves and stems during winter dormancy, but
      many of the underlying genes remain to be identified and/or verified. Transport
      of N during seasonal N cycling is a particularly weak link, since the physical
      pathways for loading and unloading of amino N to and from the phloem are poorly
      understood. Short-day photoperiod followed by decreasing temperatures are the
      environmental cues that stimulate dormancy induction, and nutrient remobilization
      and storage. However, beyond the involvement of phytochrome, very little is known
      about the signal transduction mechanisms that link environmental cues to nutrient
      remobilization and storage. We propose a model whereby nutrient transport and
      sensing plays a major role in source-sink transitions of leaves and stems during
      seasonal N cycling.

PMID- 29576081
TI  - SELENOPROTEIN O is a chloroplast protein involved in ROS scavenging and its
      absence increases dehydration tolerance in Arabidopsis thaliana.
AB  - The evolutionary conserved family of Selenoproteins performs redox-regulatory
      functions in bacteria, archaea and eukaryotes. Among them, members of the
      SELENOPROTEIN O (SELO) subfamily are located in mammalian and yeast mitochondria,
      but their functions are thus far enigmatic. Screening of T-DNA knockout mutants
      for resistance to the proline analogue thioproline (T4C), identified mutant
      alleles of the plant SELO homologue in Arabidopsis thaliana. Absence of SELO
      resulted in a stress-induced transcriptional activation instead of silencing of
      mitochondrial proline dehydrogenase, and also high elevation of Delta(1)
      pyrroline-5-carboxylate dehydrogenase involved in degradation of proline, thereby
      alleviating T4C inhibition and lessening drought-induced proline accumulation.
      Unlike its animal homologues, SELO was localized to chloroplasts of plants
      ectopically expressing SELO-GFP. The protein was co-fractionated with thylakoid
      membrane complexes, and co-immunoprecipitated with FNR, PGRL1 and STN7, all
      involved in regulating PSI and downstream electron flow. The selo mutants
      displayed extended survival under dehydration, accompanied by longer
      photosynthetic activity, compared with wild-type plants. Enhanced expression of
      genes encoding ROS scavenging enzymes in the unstressed selo mutant correlated
      with higher oxidant scavenging capacity and reduced methyl viologen damage. The
      study elucidates SELO as a PSI-related component involved in regulating ROS
      levels and stress responses.

PMID- 29576082
TI  - Emerging themes in heterotrimeric G-protein signaling in plants.
AB  - Heterotrimeric G-proteins are key signaling components involved during the
      regulation of a multitude of growth and developmental pathways in all eukaryotes.
      Although the core proteins (Galpha, Gbeta, Ggamma subunits) and their basic
      biochemistries are conserved between plants and non-plant systems, seemingly
      different inherent properties of specific components, altered wirings of G
      protein network architectures, and the presence of novel receptors and effector
      proteins make plant G-protein signaling mechanisms somewhat distinct from the
      well-established animal paradigm. G-protein research in plants is getting a lot
      of attention recently due to the emerging roles of these proteins in controlling
      many agronomically important traits. New findings on both canonical and novel G
      protein components and their conserved and unique signaling mechanisms are
      expected to improve our understanding of this important module in affecting
      critical plant growth and development pathways and eventually their utilization
      to produce plants for the future needs. In this review, we briefly summarize what
      is currently known in plant G-protein research, describe new findings and how
      they are changing our perceptions of the field, and discuss important issues that
      still need to be addressed.

PMID- 29576083
TI  - Sugar metabolism in the desiccation tolerant grass Oropetium thomaeum in response
      to environmental stresses.
AB  - Oropetium thomaeum is a desiccation tolerant grass and acquisition of desiccation
      tolerance is correlated with changes in carbohydrate metabolism. Here we address
      the question whether the changes in carbohydrate metabolism are specific to the
      dehydration process or whether other environmental factors such as high
      temperature, low temperature, hypoxia, salinity or exogenous ABA application
      trigger the same or different changes in the sugar metabolism. Fifteen different
      sugar metabolites were identified by GC/MS, including erythritol, arabinose,
      fructose, galactose, glucose, myo-inositol, sedoheptulose, sucrose, trehalose,
      galactinol, maltose, raffinose, manninotriose and stachyose. Together with
      starch, these sugars were placed into the pathways of sucrose metabolism and
      raffinose family oligosaccharides (RFOs) metabolism, as well as into the group of
      rare sugars. By comparing the changes of sugars under various stresses, we
      concluded that the changes in the sugar metabolism are both convergent and
      divergent in response to different stresses. Except for the general response to
      stress, such as starch degradation, the changes of specific sugar metabolites
      reflect a stress-specific response of O. thomaeum. Erythritol seems to be
      specific for dehydration, myo-inositol for salt stress and trehalose for hypoxia
      stress. Similar as dehydration, low temperature, salt stress and ABA application
      resulted in the accumulation of sucrose and RFOs in O. thomaeum, which indicates
      that these stresses share high similarity with dehydration. Thus it is proposed
      that sucrose and RFOs have a general protective role under these stresses. In
      contrast sucrose and RFOs did not accumulate in response to high temperature or
      hypoxia whose effects tend to be consumptive and destructive. The accumulation of
      galactose, melibiose and manninotriose demonstrate that RFOs are degraded under
      stress. The accumulation of these sugar metabolites might result from the
      reaction of RFOs and stress-produced hydroxyl radicals, which supports a possible
      role of RFOs in stress defense. In addition, ABA application led to substantial
      synthesis of stachyose which occurs only in response to dehydration, indicating
      that stachyose synthesis is possibly closely related to ABA in O. thomaeum.

PMID- 29576084
TI  - Mechanism of freeze-thaw injury and recovery: A cool retrospective and warming up
      to new ideas.
AB  - Understanding cellular mechanism(s) of freeze-thaw injury (FTI) is key to the
      efforts for improving plant freeze-tolerance by cultural methods or
      molecular/genetic approaches. However, not much work has been done in the last
      25+ years to advance our understanding of the nature and cellular loci of FTI.
      Currently, two FTI lesions are predominantly implicated: 1) structural and
      functional perturbations in plasma membrane; 2) ROS-induced oxidative damage.
      While both have stood the test of time, many questions remain unresolved and
      other potentially significant lesions need to be investigated. Additionally,
      molecular mechanism of post-thaw recovery (PTR), a critical component of frost
      survival, has not been well investigated. Mechanistic understanding of repair
      after reversible injury could expand the options for strategies to improve frost
      hardiness. In this review, without claiming to be exhaustive, I have attempted to
      synthesize major discoveries from last several decades on the mechanisms of FTI
      and the relatively little research conducted thus far on PTR mechanisms. It is
      followed by proposing of hypotheses for mechanism(s) for irreversible FTI or PTR
      involving cytosolic calcium and ROS signaling. Perspective is presented on some
      unresolved questions and research on new ideas to fill the knowledge gaps and
      advance the field.

PMID- 29576085
TI  - SsSm1, a Cerato-platanin family protein, is involved in the hyphal development
      and pathogenic process of Sclerotinia sclerotiorum.
AB  - The filamentous fungus Sclerotinia sclerotiorum is an important plant pathogen
      with a worldwide distribution. It can infect a wide variety of plants, causing
      serious disease in many types of crops, such as rapeseed, sunflower and soybean.
      Sclerotinia stem rot caused by this fungus affects main crops and has led to
      great economic loss. Elicitors are a group of compounds that inspire the host
      plant to produce an immune response against invading pathogens. This study
      describes a protein that has high homology with the Trichoderma elicitor Sm1 and
      was found in the genome of S. sclerotiorum. We named this protein SsSm1. To
      determine whether this protein has an elicitor function like its homology
      protein, we constructed a heterologous expression vector for SsSm1 and expressed
      it in Escherichia coli. The protein of heterologous expression led to the
      formation of lesions in tobacco that closely resemble hypersensitive response
      lesions. Transient expression of the encoding gene of SsSm1 in tobacco leaves
      also caused hypersensitive response. Then, RNA silencing was used to identify the
      function of SsSm1. The hyphal growth and pathogenicity of silenced transformants
      were shown to be obviously lagging and branched abnormally. Transformants
      produced less infection cushions and deformed sclerotiorum. In addition, SsSm1
      silencing caused weak tolerance to NaCl, sorbitol and SDS, and the sensitivity of
      mutants to carbendazim was also significantly decreased. Based on the above
      results, we speculate that this protein may be related to the development of
      hyphae, infection cushions and sclerotiorum, but the specific molecular mechanism
      needs to be studied further.

PMID- 29576086
TI  - PAMP-responsive ATL gene StRFP1 and its orthologue NbATL60 positively regulate
      Phytophthora infestans resistance in potato and Nicotiana benthamiana.
AB  - Ubiquitination is a post-translational modification that plays a crucial role
      during the regulation of plant immune signalling. The plant ATL family consists
      of a large number of putative RING type ubiquitin ligases. We show that potato
      ATL family gene StRFP1 and its orthologue NbATL60 from N. benthamiana both
      respond to Phytophthora infestans culture filtrate (CF) and flg22 induction.
      StRFP1 positively regulates immunity against P. infestans in potato. Ectopic
      transient expression of StRFP1 or expression of NbATL60 in N. benthamiana also
      enhances late blight resistance. By contrast, silencing NbATL60 in N. benthamiana
      reduces late blight resistance and leads to plant growth inhibition. Both StRFP1
      and NbATL60 localize to the plasma membrane and intracellular puncta and possess
      E3 Ligase activity in vitro. Furthermore we demonstrate that the RING finger
      domain mutants of StRFP1 and NbATL60 lost E3 ligase activity and fail to suppress
      P. infestans colonization in N. benthamiana, indicating that E3 ligase activity
      is critical for StRFP1 and NbATL60 to regulate immunity. Overexpression or RNA
      interference of StRFP1 in transgenic potato led to increased or decreased
      expression of PTI maker genes (WRKY7, WRKY8, ACRE31 and Pti5) respectively.
      Similarly silencing of NbATL60 in N. benthamiana decreases expression of these
      PTI marker genes. Moreover, VIGS of NbATL60 in N. benthamiana did not compromise
      P. infestans PAMP INF1 or R2/Avr2, R3a/AVR3a, Rx/Cp and Pto/AvrPto triggered cell
      death. These results indicate that ATL genes StRFP1 and NbATL60 contribute to
      basal immunity (PTI) in Solanaceous plants.

PMID- 29576087
TI  - Expression of OsWNK9 in Arabidopsis conferred tolerance to salt and drought
      stress.
AB  - With No Lysine (WNK) kinase belongs to ser/thr protein kinase group in which
      conserved catalytic lysine (K) residue of subdomain II is shifted to subdomain I.
      In this study, we cloned full-length coding region of WNK9 from Oryza sativa
      (OsWNK9) and performed in silico studies to confirm the presence of all kinase
      signature regulatory elements. The transcript analysis revealed that OsWNK9 was
      strongly down regulated under salinity, drought and ABA stress in shoots.
      Constitutive expression of OsWNK9 in Arabidopsis thaliana imparted increased
      tolerance to salt, drought, and ABA stress. Transgenic lines showed healthy
      phenotypes such as green leaves, achieved higher fresh weight and longer roots
      under salt, drought and ABA stress as compared to wild-type (WT). Transgenic
      plants showed better seed germination, higher chlorophyll retention and less
      water loss under salt and drought stress compared to WT. Promoter/gene expression
      studies revealed that OsWNK9 were expressed throughout plant tissues with higher
      expression in roots. Subcellular localization studies of OsWNK9 showed their
      presence in the nucleus. The transcript analysis of abiotic stress marker genes
      and ABA dependent genes showed they were highly expressed in transgenic lines
      compared to WT in response to salt and drought stress. The endogenous ABA level
      under salt and drought stress in transgenic lines was higher than WT. The results
      indicated that OsWNK9 may regulate salt and drought response in ABA dependent
      manner.

PMID- 29576088
TI  - Review: Potential biotechnological assets related to plant immunity modulation
      applicable in engineering disease-resistant crops.
AB  - This review emphasizes the biotechnological potential of molecules implicated in
      the different layers of plant immunity, including, pathogen-associated molecular
      pattern (PAMP)-triggered immunity (PTI), effector-triggered susceptibility (ETS),
      and effector-triggered immunity (ETI) that can be applied in the development of
      disease-resistant genetically modified (GM) plants. These biomolecules are
      produced by pathogens (viruses, bacteria, fungi, oomycetes) or plants during
      their mutual interactions. Biomolecules involved in the first layers of plant
      immunity, PTI and ETS, include inhibitors of pathogen cell-wall-degrading enzymes
      (CWDEs), plant pattern recognition receptors (PRRs) and susceptibility (S)
      proteins, while the ETI-related biomolecules include plant resistance (R)
      proteins. The biomolecules involved in plant defense PTI/ETI responses described
      herein also include antimicrobial peptides (AMPs), pathogenesis-related (PR)
      proteins and ribosome-inhibiting proteins (RIPs), as well as enzymes involved in
      plant defensive secondary metabolite biosynthesis (phytoanticipins and
      phytoalexins). Moreover, the regulation of immunity by RNA interference (RNAi) in
      GM disease-resistant plants is also considered. Therefore, the present review
      does not cover all the classes of biomolecules involved in plant innate immunity
      that may be applied in the development of disease-resistant GM crops but instead
      highlights the most common strategies in the literature, as well as their
      advantages and disadvantages.

PMID- 29576089
TI  - OsDSSR1, a novel small peptide, enhances drought tolerance in transgenic rice.
AB  - Small signaling peptides play important roles in plant development and responses
      to abiotic and biotic stresses. We have identified a novel small peptide gene in
      rice, OsDSSR1, which is expressed mainly in the root, stem, node, leaf, and
      panicle. OsDSSR1 expression is also induced by drought, salinity, ABA, and H2O2
      treatment. OsDSSR1 is localized in the nucleus and cytoplasm. Transgenic plants
      overexpressing OsDSSR1 exhibited enhanced drought stress tolerance and decreased
      ABA sensitivity as compared to the wild type. Overexpression of OsDSSR1 promoted
      the accumulation of compatible osmolytes, such as free proline and soluble
      sugars. OsDSSR1-overexpressing plants displayed enhanced OsSodCc2 and OscAPX
      expression and superoxide dismutase and ascorbate peroxidase activities under
      drought stress. RNA-sequencing data revealed that the expression of 72 abiotic
      stress-responsive genes was significantly altered in homozygous transgenic
      plants. These stress-responsive candidate genes will aid in expanding our
      understanding of the mechanisms by which small peptides mediate tolerance in crop
      species.

PMID- 29576091
TI  - Nutritional Genomics: Emerging Science with Implications for Us All.

PMID- 29576090
TI  - Morphological, transcriptomics and biochemical characterization of new dwarf
      mutant of Brassica napus.
AB  - Plant height is a key trait of plant architecture, and is responsible for both
      yield and lodging resistance in Brassica napus. A dwarf mutant line (bnaC.dwf)
      was obtained by chemical mutagenesis of an inbred line T6. However, the molecular
      mechanisms and changed biological processes of the dwarf mutant remain to be
      determined. In this study, a comparative transcriptome analysis between bnaC.dwf
      and T6 plants was performed to identify genome-wide differentially expressed
      genes (DEGs) and possible biological processes that may explain the phenotype
      variations in bnaC.dwf. As a result of this analysis, 60,134,746-60,301,384 clean
      reads were aligned to 60,074 genes in the B. napus genome, and accounted for
      60.03% of the annotated genes. In total, 819 differentially expressed genes were
      used for GO (Gene Ontology) term and KEGG (Kyoto Encyclopedia of Genes and
      Genomes) pathway enrichment analyses with a FDR (false discovery rate) criterion
      of <0.001, |log2Ratio| >= 1. We focused on plant hormone signal transduction
      pathways, plant-pathogen interaction pathway, protein phosphorylation and
      degradation pathways and sugar metabolism pathways. Taken together, the decrease
      in local auxin (IAA) levels, the variation in BnTCH4, BnKAN1, BnERF109, COI1-JAZ9
      MYC2, auxin response genes (BnGH3.11, BnSAUR78, and AUX/IAA19), and ABA (abscisic
      acid) signaling genes (BnADP5, BnSnRK2.1, BnABF3.1) partially accounted for
      variations of cell proliferation in internodes, shoot and root apical meristem
      maintenance, abiotic and biotic stress resistance, and pre-harvest sprouting. As
      a comprehensive consequence of the cross-talk between plant hormones, sugar
      metabolism, plant-pathogen interactions and protein metabolism, bnaC.dwf presents
      distinct phenotypes from T6. These results will be helpful for shedding light on
      molecular mechanisms in the dwarf mutant, and give insight into further molecular
      breeding of semi-dwarf B. napus.

PMID- 29576092
TI  - Position of the Academy of Nutrition and Dietetics: Individualized Nutrition
      Approaches for Older Adults: Long-Term Care, Post-Acute Care, and Other Settings.
AB  - It is the position of the Academy of Nutrition and Dietetics that the quality of
      life and nutritional status of older adults in long-term care, post-acute care,
      and other settings can be enhanced by individualized nutrition approaches. The
      Academy advocates that as part of the interprofessional team, registered
      dietitian nutritionists assess, evaluate, and recommend appropriate nutrition
      interventions according to each individual's medical condition, desires, and
      rights to make health care choices. Nutrition and dietetic technicians,
      registered assist registered dietitian nutritionists in the implementation of
      individualized nutrition care, including the use of least restrictive diets.
      Health care practitioners must assess risks vs benefits of therapeutic diets,
      especially for frail older adults. Food is an essential component of quality of
      life; an unpalatable or unacceptable diet can lead to poor food and fluid intake,
      resulting in malnutrition and related negative health effects. Including older
      individuals in decisions about food can increase the desire to eat and improve
      quality of life.

PMID- 29576093
TI  - Academy of Nutrition and Dietetics: Revised 2017 Standards of Practice and
      Standards of Professional Performance for Registered Dietitian Nutritionists
      (Competent, Proficient, and Expert) in Oncology Nutrition.
AB  - Oncology nutrition encompasses nutrition care for individuals along the cancer
      care continuum. Nutrition is a vital component of prevention, treatment, and
      healthy survivorship. The practice of an oncology registered dietitian
      nutritionist (RDN) reflects the setting and population served with diverse cancer
      diagnoses, including expanded roles and responsibilities reflecting the RDN's
      interests and organization's activities. Provision of nutrition services in
      oncology requires that RDNs have advanced knowledge in the focus area of oncology
      nutrition. Thus, the Oncology Nutrition Dietetic Practice Group, with guidance
      from the Academy of Nutrition and Dietetics Quality Management Committee, has
      developed Standards of Practice and Standards of Professional Performance as
      tools for RDNs currently in practice or interested in working in oncology
      nutrition, to address their current skill level and to identify areas for
      additional professional development in this practice area. The Standards of
      Practice address and apply the Nutrition Care Process and workflow elements,
      which are screening, assessment, diagnosis, intervention, evaluation/monitoring,
      and discharge planning and transitions of care. The Standards of Professional
      Performance consist of the following six domains of professionalism including:
      Quality in Practice, Competence and Accountability, Provision of Services,
      Application of Research, Communication and Application of Knowledge, and
      Utilization and Management of Resources. Within each standard, specific
      indicators provide measurable action statements and describe three skill levels
      (competent, proficient, and expert) for RDNs working in oncology nutrition.

PMID- 29576094
TI  - Closing the Gap in Nutrition Care at Outpatient Cancer Centers: Ongoing
      Initiatives of the Oncology Nutrition Dietetic Practice Group.

PMID- 29576095
TI  - 2018 Academy Member Benefits Update.

PMID- 29576096
TI  - The Academy of Nutrition and Dietetics' Priorities in the 2018 Farm Bill.

PMID- 29576097
TI  - Erratum.

PMID- 29576098
TI  - How Can Providers Get Payment for Medical Nutrition Therapy When the Diagnosis Is
      Not Explicitly Covered?

PMID- 29576099
TI  - From 'goal-directed haemodynamic therapy' to 'individualised perioperative
      haemodynamic management'.

PMID- 29576100
TI  - Monkey business: the importance of mounting behavioural evidence for anaesthesia
      induced developmental neurotoxicity.

PMID- 29576101
TI  - Quest for new drugs: a way to solve anaesthesia neurotoxicity?

PMID- 29576102
TI  - Mode of anaesthesia for Caesarean delivery and maternal morbidity: can we
      overcome confounding by indication?

PMID- 29576103
TI  - Analysing tidal volumes early after a positive end-expiratory pressure increase:
      a new way to determine optimal PEEP in the operating theatre?

PMID- 29576104
TI  - The dark ages of maternal sepsis: time to be enlightened.

PMID- 29576105
TI  - Perioperative management of patients with congenital or acquired disorders of the
      QT interval.
AB  - QT prolongation can be attributable to various causes that can be categorised as
      acquired or congenital. Arrhythmias related to QT prolongation can result in
      clinical presentations, such as syncope and sudden cardiac death. The
      perioperative period presents a number of issues that may affect a patient's risk
      of developing polymorphic ventricular tachycardia or torsades de pointes.
      Although most patients may have an unremarkable perioperative course, some may
      have complications; this review article aims to help clinicians avoid potential
      complications, and to help them address treatment for perioperative issues that
      may occur.

PMID- 29576106
TI  - Emergency care of patients receiving non-vitamin K antagonist oral
      anticoagulants.
AB  - Non-vitamin K antagonist oral anticoagulants (NOACs), which inhibit thrombin
      (dabigatran) and factor Xa (rivaroxaban, apixaban, edoxaban) have been introduced
      in several clinical indications. Although NOACs have a favourable benefit-risk
      profile and can be used without routine laboratory monitoring, they are
      associated-as any anticoagulant-with a risk of bleeding. In addition, treatment
      may need to be interrupted in patients who need surgery or other procedures. The
      objective of this article, developed by a multidisciplinary panel of experts in
      thrombosis and haemostasis, is to provide an update on the management of NOAC
      treated patients who experience a bleeding episode or require an urgent
      procedure. Recent advances in the development of targeted reversal agents are
      expected to help streamline the management of NOAC-treated patients in whom rapid
      reversal of anticoagulation is required.

PMID- 29576107
TI  - Steroids in cardiac surgery: a systematic review and meta-analysis.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction
      that may contribute to postoperative complications. Preventing this reaction with
      steroids may improve outcomes. We performed a systematic review to evaluate the
      impact of prophylactic steroids on clinical outcomes in patients undergoing on
      pump cardiac surgery. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL
      for randomised controlled trials (RCTs) comparing perioperative corticosteroid
      administration with a control group in adults undergoing CPB. Outcomes of
      interest included mortality, myocardial infarction, and new onset atrial
      fibrillation. We assessed the quality of evidence using the Grading of
      Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty
      six RCTs published between 1977 and 2015 were included in this meta-analysis.
      Mortality was not significantly different between groups [3.0% (215/7258
      patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group;
      relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I2 =
      0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989
      patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31;
      P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group
      [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91,
      95% CI, 0.86-0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small
      trials (P for interaction <0.00001). CONCLUSIONS: After randomising 16 013
      patients, steroid administration at the time of cardiac surgery had an unclear
      impact on mortality, increased the risk of myocardial injury, and the impact on
      atrial fibrillation should be viewed with caution given that large trials showed
      no effect.

PMID- 29576108
TI  - Efficacy and adverse effects of buprenorphine in acute pain management:
      systematic review and meta-analysis of randomised controlled trials.
AB  - Buprenorphine appears to have a ceiling effect on respiratory depression, but not
      analgesia in healthy young patients. However, the efficacy and side-effects of
      buprenorphine in the setting of acute pain are poorly characterized. The aim of
      this study was to characterize the analgesic efficacy and adverse effects of
      buprenorphine compared with morphine in the acute pain setting. A systematic
      review of five databases was performed. Randomised controlled trials (RCTs)
      comparing buprenorphine with morphine in acute pain management were included.
      Studies performed outside of the hospital setting were excluded. The a priori
      primary outcomes included pain, respiratory depression, and sedation. Secondary
      outcomes included requirement for rescue analgesia, time to rescue analgesia,
      nausea, vomiting, dizziness, hypotension, and pruritus. Twenty-eight RCTs with
      2210 patients met the inclusion criteria. There was no difference in pain [visual
      analogue scale weighted mean difference (WMD)=-0.29; 95% confidence interval
      (CI)=-0.62 to 0.03; I2=99%; P=0.07], incidence of respiratory depression [odds
      ratio (OR)=2.07; 95% CI=0.78-5.51; I2=30%; P=0.14], or sedation (OR=1.44; 95%
      CI=0.76-2.74; I2=23%; P=0.26). There was only one secondary outcome with an
      overall significant difference; buprenorphine use was associated with
      significantly less pruritus (OR=0.31; 95% CI=0.12-0.84; I2=6%; P=0.02). Whilst a
      theoretical ceiling effect may exist with respect to buprenorphine and
      respiratory depression, in a clinical setting, it can still cause significant
      adverse effects on respiratory function. However, given that buprenorphine is an
      equally efficacious analgesic agent, it is a useful alternative opioid because of
      its ease of administration and reduced incidence of pruritus.

PMID- 29576109
TI  - Should continuous rather than single-injection interscalene block be routinely
      offered for major shoulder surgery? A meta-analysis of the analgesic and side
      effects profiles.
AB  - BACKGROUND: Major shoulder surgery is associated with moderate-to-severe pain,
      but consensus on the optimal analgesic approach is lacking. Continuous catheter
      based interscalene block (CISB) prolongs the analgesic benefits of its single
      injection counterpart (SISB), but concerns over CISB complications and
      difficulties in interpreting comparative evidence examining major and minor
      shoulder procedures simultaneously, despite their differences in postoperative
      pain, have limited CISB popularity. This meta-analysis evaluates the CISB
      analgesic role and complications compared with SISB for major shoulder surgery.
      METHODS: We retrieved randomised controlled trials (RCTs) comparing the effects
      of CISB to SISB on analgesic outcomes and side-effects after major shoulder
      surgery. Postoperative opioid consumption at 24 h was designated as the primary
      outcome. Secondary outcomes included 24-48 h opioid consumption, postoperative
      rest and dynamic pain scores up to 72 h, time-to-first analgesic, recovery room
      and hospital stay durations, patient satisfaction, postoperative nausea and
      vomiting, respiratory function, and block-related complications. RESULTS: Data
      from 15 RCTs were pooled using random-effects modelling. Compared with SISB, CISB
      reduced 24- and 48-h oral morphine consumption by a weighted mean difference [95%
      confidence interval] of 50.9 mg [-81.6, -20.2], (P=0.001) and 44.7 mg [-80.9, 
      8.7], (P<0.0001), respectively. Additionally, CISB provided superior rest and
      dynamic pain control beyond 48 h, prolonged time-to-first analgesic, enhanced
      satisfaction, and reduced postoperative nausea and vomiting without
      complications. CISB caused an 11.0-11.7% decrease in respiratory indices. Result
      heterogeneity was successfully explained. CONCLUSIONS: High-level evidence
      indicates that CISB provides superior analgesia up to 48 h after major shoulder
      surgery, without increasing side-effects, compared with SISB. The importance of
      CISB-related changes in respiratory indices is questionable.

PMID- 29576110
TI  - Haematoma and abscess after neuraxial anaesthesia: a review of 647 cases.
AB  - Although rare, spinal haematoma and abscess after central neuraxial blocks may
      cause severe permanent neurological injury. Optimal treatment and outcome remain
      unclear. In order to identify possible predisposing patient characteristics and
      describe the ensuing clinical course, we searched Medline, Embase, and the
      Cochrane Library for reports of spinal haematomas and abscesses associated with
      central neuraxial blocks. Extracted data included patient characteristics,
      symptoms, treatment, and outcome. We analysed 409 reports, including 647 patients
      (387 patients with spinal haematoma and 260 patients with spinal abscess). Spinal
      haematoma and abscess occurred predominantly after epidural anaesthesia (58% and
      83%, respectively). Neurological recovery was correlated with the severity of
      initial neurological deficit. When decompression of spinal haematoma was delayed
      for >12 h after clinical diagnosis, neurological outcome was worse compared with
      earlier decompression (odds ratio 4.5, 95% confidence interval 2.1-9.9, P<0.001,
      n=163). After spinal haematoma, 47% of published patients had full recovery, 28%
      had partial recovery, and in 25% no recovery was observed. Good outcome after
      conservative management was observed in patients with mild symptoms or with
      spontaneous recovery during the diagnostic and therapeutic workup. After spinal
      abscess, 68% of reported patients recovered fully, 21% showed partial recovery,
      and no recovery was reported in 11%. Persistent neurological symptoms after
      spinal haematoma and abscess are common and correlate with the severity of
      initial neurological deficit. Neurological outcome seems worse when decompressive
      surgery of haematoma is delayed. Notwithstanding the considerable risk of
      selection bias and publication bias, conservative management may be feasible in
      patients with mild symptoms or spontaneous recovery.

PMID- 29576111
TI  - Systematic review and consensus definitions for the Standardised Endpoints in
      Perioperative Medicine (StEP) initiative: patient comfort.
AB  - BACKGROUND: Maximising patient comfort during and after surgery is a primary
      concern of anaesthetists and other perioperative clinicians, but objective
      measures of what constitutes patient comfort in the perioperative period remain
      poorly defined. The Standardised Endpoints in Perioperative Medicine initiative
      was established to derive a set of standardised endpoints for use in
      perioperative clinical trials. METHODS: We undertook a systematic review to
      identify measures of patient comfort used in the anaesthetic, surgical, and other
      perioperative literature. A multi-round Delphi consensus process that included up
      to 89 clinician researchers was then used to refine a recommended list of outcome
      measures. RESULTS: We identified 122 studies in a literature search, which were
      the basis for a preliminary list of 24 outcome measures and their definitions.
      The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79),
      and 100% (n=13), respectively. A final list of six defined endpoints was
      identified: pain intensity (at rest and during movement) at 24 h postoperatively,
      nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery
      (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to
      mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will
      support benchmarking and pooling (meta-analysis) of trials, one or more of these
      recommended endpoints should be considered for inclusion in clinical trials
      assessing patient comfort and pain after surgery.

PMID- 29576112
TI  - Videolaryngoscopy versus direct laryngoscopy for emergency orotracheal intubation
      outside the operating room: a systematic review and meta-analysis.
AB  - Videolaryngoscopy (VL) may improve the success of orotracheal intubation compared
      with direct laryngoscopy (DL). We performed a systematic search of PubMed,
      Embase, and CENTRAL databases for studies comparing VL and DL for emergency
      orotracheal intubations outside the operating room. The primary outcome was rate
      of first-pass intubation, with subgroup analyses by location, device used,
      clinician experience, and clinical scenario. The secondary outcome was
      complication rates. Data are presented as [odds ratio (95% confidence intervals);
      P-values]. We identified 32 studies with 15 064 emergency intubations. There was
      no difference in first-pass intubation with VL compared with DL [OR=1.28, (0.99
      1.65); P=0.06]. First-pass intubations were increased with VL compared with DL in
      the intensive care unit (ICU) [2.02 (1.43-2.85); P<0.001], and similar in the
      emergency department or pre-hospital setting. First-pass intubations were similar
      with GlideScope(r), but improved with the CMAC(r) [1.32 (1.08-1.62); P=0.007]
      compared with DL. There was greater first-pass intubation with VL compared with
      DL amongst novice/trainee clinicians [OR=1.95 (1.45-2.64); P<0.001], but not
      amongst experienced clinicians or paramedics/nurses. There was no difference in
      first-pass intubation with VL compared with DL during cardiopulmonary
      resuscitation or trauma. VL compared with DL was associated with fewer
      oesophageal intubations [OR=0.32 (0.14-0.70); P=0.003], but more arterial
      hypotension [OR=1.49 (1.00-2.23); P=0.05]. In summary, VL compared with DL is
      associated with greater first-pass emergency intubation in the ICU and amongst
      less experienced clinicians, and reduces oesophageal intubations. However, VL is
      associated with greater incidence of arterial hypotension. Further trials
      investigating the utility of VL over DL in specific situations are required.

PMID- 29576113
TI  - Incidence of thrombosis in perioperative and non-operative myocardial infarction.
AB  - BACKGROUND: The contribution of thrombosis to the aetiology of perioperative
      myocardial infarction (MI) is uncertain. We used optical coherence tomography
      (OCT) to determine the presence of thrombus and plaque morphology in patients
      experiencing a perioperative MI and matched patients experiencing a non-operative
      MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study.
      Thirty patients experiencing a perioperative MI and 30 matched patients
      experiencing a non-operative MI, without ST elevation, underwent OCT to determine
      the presence of thrombus and culprit lesion plaque morphology. Angiography and
      OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset
      of perioperative and non-operative MI, respectively. OCT images were evaluated by
      an independent core laboratory without knowledge of whether the patient had
      suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at
      the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative
      MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01.
      The only non-culprit lesion with thrombus was in a perioperative MI patient who
      also had a culprit lesion thrombus. Perioperative and non-operative MI culprit
      lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%),
      respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five
      patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%)
      suffered a cardiac death and no non-operative MI patient died during the 30-day
      follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non
      operative MI, despite similar underlying plaque morphology.

PMID- 29576114
TI  - Effect of goal-directed haemodynamic therapy on postoperative complications in
      low-moderate risk surgical patients: a multicentre randomised controlled trial
      (FEDORA trial).
AB  - BACKGROUND: The aim of this study was to evaluate postoperative complications in
      patients having major elective surgery using oesophageal Doppler monitor-guided
      goal-directed haemodynamic therapy (GDHT), in which administration of fluids,
      inotropes, and vasopressors was guided by stroke volume, mean arterial pressure,
      and cardiac index. METHODS: The FEDORA trial was a prospective, multicentre,
      randomised, parallel-group, controlled patient- and observer-blind trial
      conducted in adults scheduled for major elective surgery. Randomization and
      allocation were carried out by a central computer system. In the control group,
      intraoperative fluids were given based on traditional principles. In the GDHT
      group, the intraoperative goals were to maintain a maximal stroke volume, with
      mean arterial pressure >70 mm Hg, and cardiac index >=2.5 litres min-1 m-2. The
      primary outcome was percentage of patients with moderate or severe postoperative
      complications during the first 180 days after surgery. RESULTS: In total, 450
      patients were randomized to the GDHT group (n=224) or control group (n=226). Data
      from 420 subjects were analysed. There were significantly fewer with
      complications in the GDHT group (8.6% vs 16.6%, P=0.018). There were also fewer
      complications (acute kidney disease, pulmonary oedema, respiratory distress
      syndrome, wound infections, etc.), and length of hospital stay was shorter in the
      GDHT group. There was no significant difference in mortality between groups.
      CONCLUSIONS: Oesophageal Doppler monitor-guided GDHT reduced postoperative
      complications and hospital length of stay in low-moderate risk patients
      undergoing intermediate risk surgery, with no difference in mortality at 180
      days. CLINICAL TRIAL REGISTRATION: ISRCTN93543537.

PMID- 29576116
TI  - Persistent alteration in behavioural reactivity to a mild social stressor in
      rhesus monkeys repeatedly exposed to sevoflurane in infancy.
AB  - BACKGROUND: Socio-emotional development is the expression and management of
      emotions, which in non-human primates can be examined using responses toward
      increasing levels of threat. Damage to the limbic system alters socio-emotional
      development in primates. Thus, neuronal and glial cell loss caused by exposure to
      general anaesthesia early in infancy might also impact socio-emotional
      development. We recently reported that repeated sevoflurane exposure in the first
      month of life alters emotional behaviours at 6 months of age and impairs visual
      recognition memory after the first year of life in rhesus monkeys. The present
      study evaluated socio-emotional behaviour at 1 and 2 yr of age in those same
      monkeys to determine the persistence of altered emotional behaviour. METHODS:
      Rhesus monkeys of both sexes were exposed to sevoflurane anaesthesia three times
      for 4 h each time in the first 6 weeks of life. At 1 and 2 yr of age, they were
      tested on the human intruder task, a well-established mild acute social stressor.
      RESULTS: Monkeys exposed to sevoflurane as infants exhibited normal fear and
      hostile responses, but exaggerated self-directed (displacement) behaviours, a
      general indicator of stress and anxiety in non-human primates. CONCLUSIONS: Early
      repeated sevoflurane exposure in infant non-human primates results in an anxious
      phenotype that was first detected at 6 months, and persists for at least 2 yr of
      age. This is the first demonstration of such a prolonged impact of early
      anaesthesia exposure on emotional reactivity.

PMID- 29576115
TI  - Inhibition of RhoA reduces propofol-mediated growth cone collapse, axonal
      transport impairment, loss of synaptic connectivity, and behavioural deficits.
AB  - BACKGROUND: Exposure of the developing brain to propofol results in cognitive
      deficits. Recent data suggest that inhibition of neuronal apoptosis does not
      prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis
      play a role in anaesthetic neurotoxicity. Proper neuronal growth during
      development is dependent upon growth cone morphology and axonal transport.
      Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent
      depolymerisation of actin, and reduces dendritic spines and synapses. We
      hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive
      deficits. The present study tested whether RhoA inhibition with the botulinum
      toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and
      preserves cognitive function. METHODS: RhoA activation, growth cone morphology,
      and axonal transport were measured in neonatal rat neurones (5-7 days in vitro)
      exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation
      (Golgi-Cox), and network connectivity were measured in mice (age 28 days)
      previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult
      mice (age 3 months) previously exposed to propofol at postnatal day 5-7. RESULTS:
      Propofol increased RhoA activation, collapsed growth cones, and impaired
      retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic
      factor, all of which were prevented with TAT-C3. Adult mice previously treated
      with propofol had decreased numbers of total hippocampal synapses and presynaptic
      vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy
      fibres. These mice also exhibited decreased hippocampal-dependent contextual fear
      memory recall. All anatomical and behavioural changes were prevented with TAT-C3
      pre-treatment. CONCLUSION: Inhibition of RhoA prevents propofol-mediated
      hippocampal neurotoxicity and associated cognitive deficits.

PMID- 29576118
TI  - Association between mode of anaesthesia and severe maternal morbidity during
      admission for scheduled Caesarean delivery: a nationwide population-based study
      in Japan, 2010-2013.
AB  - BACKGROUND: Although the incidence of maternal mortality during Caesarean
      delivery remains very low, the rate of severe maternal morbidity is increasing.
      Improvements in obstetric anaesthetic practice have resulted in a dramatic
      reduction in the risk of maternal death from general anaesthesia. Less clear is
      whether the risk of severe maternal morbidity differs according to mode of
      anaesthesia for women undergoing Caesarean delivery. We analysed the association
      between the mode of anaesthesia and severe maternal morbidity during Caesarean
      delivery using a nationally representative inpatient database. METHODS: We
      identified 89 225 women undergoing scheduled Caesarean delivery from the
      Diagnosis Procedure Combination database in Japan, 2010-2013. We defined severe
      maternal morbidity as the presence of any life-threatening complications and
      identified women with severe maternal morbidity from the database. Propensity
      score-matched analysis was carried out to compare the odds of severe maternal
      morbidity between women who underwent general vs neuraxial anaesthesia. RESULTS:
      Of 89 225 women, 10 058 received general anaesthesia and 79 167 received
      neuraxial anaesthesia. In the propensity score-matched analysis with 10 046
      pairs, a higher incidence of severe maternal morbidity was observed among
      patients receiving general (2.00%) rather than neuraxial anaesthesia (0.76%). The
      odds ratio of severe maternal morbidity was 2.68 (95% CI, 1.97-3.64) among women
      receiving general compared with neuraxial anaesthesia. CONCLUSIONS: For scheduled
      Caesarean delivery, general anaesthesia compared with neuraxial anaesthesia is
      associated with greater odds for severe maternal morbidity. However, we should be
      cautious with interpretation of these findings because they may be explained by
      confounding indications.

PMID- 29576117
TI  - A neurosteroid analogue with T-type calcium channel blocking properties is an
      effective hypnotic, but is not harmful to neonatal rat brain.
AB  - BACKGROUND: More than 4 million children are exposed annually to sedatives and
      general anaesthetics (GAs) in the USA alone. Recent data suggest that common GAs
      can be detrimental to brain development causing neurodegeneration and long-term
      cognitive impairments. Challenged by a recent US Food and Drug Administration
      (FDA) warning about potentially neurotoxic effects of GAs in children, there is
      an urgent need to develop safer GAs. METHODS: Postnatal Day 7 (P7) rat pups of
      both sexes were exposed to six (repeated every 2 h) injections of equipotent
      hypnotic doses of ketamine or the neuroactive steroid (3beta,5beta,17beta)-3
      hydroxyandrostane-17-carbonitrile (3beta-OH) for 12 h. Loss of righting reflex
      was used to assess hypnotic properties and therapeutic index; quantitative
      caspase-3 immunohistochemistry was used to assess developmental neuroapoptosis;
      patch-clamp recordings in acute brain slices were used to assess the effects of
      3beta-OH on neuronal excitability and synaptic transmission. Cognitive abilities
      of rats exposed to ketamine, 3beta-OH, or vehicle at P7 were assessed in young
      adulthood using the radial arm maze. RESULTS: The neuroactive steroid 3beta-OH
      has a therapeutic index similar to ketamine, a commonly used clinical GA. We
      report that 3beta-OH is safe and, unlike ketamine, does not cause neuroapoptosis
      or impair cognitive development when administered to P7 rat pups. Interestingly,
      3beta-OH blocks T-type calcium channels and presynaptically dampens synaptic
      transmission at hypnotically-relevant brain concentrations, but it lacks a direct
      effect on gamma-aminobutyric acid A or glutamate-gated ion channels. CONCLUSIONS:
      The neurosteroid 3beta-OH is a relatively safe hypnotic that warrants further
      consideration for paediatric anaesthesia.

PMID- 29576119
TI  - Pain after orthopaedic surgery: differences in patient reported outcomes in the
      United States vs internationally. An observational study from the PAIN OUT
      dataset.
AB  - BACKGROUND: A previous PAIN OUT study found that American orthopaedic-surgical
      patients rated 'worst pain' higher than did similar European patients. This study
      aims to confirm these findings in a larger, international patient sample, explore
      whether risk factors for greater postoperative pain exist disproportionately in
      the American population, and confirm the findings for one procedure. METHODS:
      Surveyors collected patient reported outcomes (PROs) and perioperative pain
      management practices using PAIN OUT methodology. Most PROs used 11-point
      numerical rating scales (0=null, 10=worst possible). Risk factors included:
      female gender, younger age, high BMI, chronic pain, and opioid use before
      surgery. Initial analysis used a mixed patient cohort. A secondary analysis used
      only patients undergoing total knee replacement (TKR). Inference was based
      primarily on effect size using Cohen's d. RESULTS: 13,770 patients in 13 European
      and non-European countries (international ) and 564 patients from the United
      States (US) contributed data on the 1st postoperative day. Three of 11 PROs
      differed between the cohorts: 'worst pain' {US 7.5 (2.5) vs international 5.6
      (2.8); d=0.66 [confidence interval (CI) 0.58-0.75]}; proportion 'receiving
      information about treatment options' [US 0.86 vs international 0.66; d=0.53 (CI
      0.39-0.66)]; reporting adverse effects and their severity [US 0.87 vs
      international 0.73; d=0.52 (CI 0.38-0.66)]. Risk factors did not differ between
      the two cohorts. PROs and management patterns in TKR patients were similar to the
      mixed cohort. CONCLUSIONS: Three PROs differed between international and US
      patients, with higher 'worst pain' for US patients. Neither risk factors, nor
      patient mix accounted for the observed differences for 'worst pain'. CLINICAL
      TRIAL REGISTRATION: NCT 02083835.

PMID- 29576120
TI  - Pattern of perioperative gabapentinoid use and risk for postoperative naloxone
      administration.
AB  - BACKGROUND: Single preoperative gabapentinoid (gabapentin and pregabalin)
      administration has been associated with respiratory depression during Phase I
      anaesthesia recovery. In this study, we assess for associations between chronic
      (home) use and perioperative administration (preoperative and postoperative) of
      gabapentinoids, and risk for severe over-sedation or respiratory depression as
      inferred from the use of naloxone. METHODS: From 2011 to 2016, we identified
      patients undergoing general anaesthesia discharged to standard postoperative
      wards and administered naloxone within 48 h of surgery in a single centre. These
      patients were 2:1 matched on age, sex, and type of procedure. Patient and
      perioperative characteristics were abstracted and compared to assess for risk for
      naloxone administration. RESULTS: We identified 128 patients that received
      naloxone after operation [odds ratio 1.2; 95% confidence interval (CI) 1.0, 1.4
      per 1000 general anaesthetics]. Patients on chronic or postoperative
      gabapentinoid therapy were at significantly higher risk for receiving naloxone
      after operation. Multivariable analysis detected significant interactions between
      chronic and postoperative use of gabapentinoids, where continuation of chronic
      gabapentinoid medications into the postoperative period was associated with an
      increased rate of naloxone administration (6.30, 95% CI 2.4, 16.7; P=0.001).
      Obstructive sleep apnoea (P=0.005) and preoperative disability (P=0.003) were
      also associated with an increased risk for postoperative naloxone administration.
      Patients who received naloxone had longer hospital stays and higher rates of
      postoperative delirium. CONCLUSIONS: Continuation of chronic gabapentinoid
      medications into the postoperative period is associated with the increased use of
      naloxone to reverse over-sedation or respiratory depression. Such patients
      requiring this therapy warrant high levels of postoperative monitoring.

PMID- 29576121
TI  - Anti-nociceptive effects of caloric restriction on neuropathic pain in rats
      involves silent information regulator 1.
AB  - BACKGROUND: Caloric restriction (CR) increases both average and maximum lifespan,
      retards physiological signs of ageing, and delays the onset of several diseases
      and may mediate neuropathic pain. Neuropathic pain seriously affects the quality
      of life of patients. In this study, we investigated whether CR exerts anti
      nociceptive effects on neuropathic pain, and probed its potential mechanisms.
      METHODS: Adult rats were divided into two dietary groups: an ad libitum (AL)-fed
      group and a CR group, which was provided with 60% of the food intake of AL rats
      for 6 weeks. The effects of 6-week CR on pain behaviour and neuro-inflammation
      induced by chronic constriction injury of the sciatic nerve were evaluated.
      RESULTS: Rats subjected to a CR diet had reduced hypersensitivity to mechanical
      and thermal stimuli after nerve-constriction injury. CR increased the silent
      information regulator 1 (SIRT1) expression, and suppressed the nerve-constriction
      induced production of mitochondrial-derived reactive oxygen species and
      activation of nuclear factor kappa B accompanied by suppression of mature
      interleukin-1beta production in the ipsilateral spinal cord dorsal horn. The
      inhibition of SIRT1 reversed the effects of caloric restriction on pain
      behaviours. Moreover, CR decreased the phosphorylation of N-methyl-d-aspartate
      receptor subunits and the mitogen-activated protein kinase family, decreased the
      sensory neurone excitability, and inhibited the nerve-constriction-induced glial
      cell activation. CONCLUSIONS: These results suggest that the effects of CR on
      pain behaviours in a rat model of nerve injury are via inhibition of excessive
      neuro-inflammation induced by the injury. CR may be of benefit in patients with
      neuropathic pain.

PMID- 29576122
TI  - Ketamine and norketamine attenuate oxycodone tolerance markedly less than that of
      morphine: from behaviour to drug availability.
AB  - BACKGROUND: Ketamine attenuates morphine tolerance by antagonising N-methyl-d
      aspartate receptors. However, a pharmacokinetic interaction between morphine and
      ketamine has also been suggested. The interaction between oxycodone and ketamine
      is unclear. We studied the effects of ketamine and norketamine on the attenuation
      of morphine and oxycodone tolerance focusing on both the pharmacodynamic and
      pharmacokinetic interactions. METHODS: Morphine 9.6 mg day-1 or oxycodone 3.6 mg
      day-1 was delivered to Sprague-Dawley rats by subcutaneous pumps. Once tolerance
      had developed, the rats received subcutaneous injections of ketamine or
      norketamine. Tail-flick, hot-plate, and rotarod tests were performed. Drug
      concentrations were measured with high-performance liquid chromatography-tandem
      mass spectrometry. RESULTS: Anti-nociceptive tolerance to morphine and oxycodone
      developed similarly by Day 6. Acute ketamine 10 mg kg-1 and norketamine 30 mg kg
      1 attenuated morphine tolerance for 120 and 150 min, respectively, whereas in
      oxycodone-tolerant rats the effect lasted only 60 min. Both ketamine and
      norketamine increased the brain and serum concentrations of morphine, and
      inhibited its metabolism to morphine-3-glucuronide, whereas oxycodone
      concentrations were not changed. Morphine, but not oxycodone, pretreatment
      increased the brain and serum concentrations of ketamine and norketamine.
      Ketamine, but not norketamine, significantly impaired the motor coordination.
      CONCLUSIONS: Ketamine and norketamine attenuated morphine tolerance more
      effectively than oxycodone tolerance. Ketamine and norketamine increased
      morphine, but not oxycodone brain concentrations, which may partly explain this
      difference. Norketamine is effective in attenuating morphine tolerance with minor
      effects on motor coordination. These results warrant pharmacokinetic studies in
      patients who are co-treated with ketamine and opioids.

PMID- 29576124
TI  - Cutaneous innervation of the hand: clinical testing in volunteers shows high
      intra- and inter-individual variability.
AB  - BACKGROUND: Many clinicians require a solid understanding of the anatomical areas
      supplied by specific peripheral nerves. Virtually all pertinent medical textbooks
      claim that the entire (palmar and dorsal) surface of the hand is supplied by
      three (median, radial, and ulnar) nerves and that each of these covers a well
      defined area. This study was designed to evaluate the sensory-distribution
      pattern of peripheral nerves in the hand. METHODS: Twelve volunteers were
      enrolled and randomly allocated to have median, ulnar, or radial nerve blocks to
      each hand on three successive days. All blocks were performed using ultrasound
      guidance. A neurologist carried out pinprick testing to define the sensory
      distribution area of each procedure. The hand surface was then scanned, and the
      sensory-distribution area of the blocked nerve was traced, measured, and
      quantified in relation to the entire hand surface for descriptive and comparative
      statistical analyses. RESULTS: The sensory-distribution areas of the three nerves
      revealed a high degree of inter-individual and intra-individual variabilities.
      Sizeable areas were not covered by any of the three nerves, again involving great
      variability. Conversely, 15 of the 24 hands showed areas of overlapping supply
      from more than one nerve. CONCLUSIONS: Our findings suggest that the anatomical
      areas supplied by peripheral nerves are characterised by much greater variability
      than is routinely claimed. CLINICAL TRIAL REGISTRATION: DRKS00010707.

PMID- 29576123
TI  - Role of spinal cyclooxygenase-2 and prostaglandin E2 in fentanyl-induced
      hyperalgesia in rats.
AB  - BACKGROUND: Accumulated evidence suggests that spinal cyclooxygenase-2 (COX-2)
      and prostaglandin E2 (PGE2) may be implicated in the development of opioid
      induced hyperalgesia. METHODS: Rats received subcutaneous fentanyl injections at
      different doses (20-80 MUg kg-1), four separate times at 15-min intervals. Some
      rats only received fentanyl (60 MUg kg-1 * 4 doses) with or without surgical
      incision. Fentanyl-induced hyperalgesia was evaluated via a tail-pressure or paw
      withdrawal test. The concentrations of spinal COX-2, EP-1 receptor (EP-1R) mRNA,
      and PGE2 were measured. The effects of the COX-2 inhibitor, parecoxib
      (intraperitoneal 10 mg kg-1), or the EP-1R antagonist, SC51089 (intraperitoneal
      100 MUg kg-1), on hyperalgesia and spinal PGE2 were examined. RESULTS: Acute
      repeated injections of fentanyl dose-dependently induced mechanical hyperalgesia,
      which reached a peak at the 1st day and persisted for 1-4 days postinjection.
      This hyperalgesia could be partly or totally prevented by the pretreatment of
      either parecoxib or SC51089. Consistently, the levels of spinal COX-2 mRNA and
      PGE2 were also dose-dependently increased, reaching a peak at the first day and
      persisting for 2 days postinjection. Pretreatment with parecoxib could block the
      increase in spinal PGE2 and had no effects on spinal COX-2 and EP-1R mRNA.
      Fentanyl injection enhanced incision-induced mechanical and thermal hyperalgesia.
      CONCLUSIONS: Acute repeated fentanyl administration dose-dependently produced
      mechanical hyperalgesia and augmented surgery induced postoperative hyperalgesia.
      This behavioural change was paralleled with an increase in spinal COX-2 mRNA and
      PGE2 after fentanyl administration. Inhibition of COX-2 or blockade of EP-1R can
      partly or totally prevent hyperalgesia.

PMID- 29576125
TI  - Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local
      anaesthetic infusion analgesia or both after non-ambulatory breast-cancer
      surgery: a prospective, randomised, double-blind trial.
AB  - BACKGROUND: Pectoral plane blocks (PECs) are increasingly used in analgesia for
      patients undergoing breast surgery, and were recently found to be at least
      equivalent to single-shot paravertebral anaesthesia. However, there are no data
      comparing PECs with the popular practice of continuous local anaesthetic wound
      infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the
      efficacy and safety of PECs blocks with LA infusion, or a combination of both in
      patients undergoing non-ambulatory breast-cancer surgery. METHODS: This single
      centre, prospective, randomised, double-blind trial analysed 45 women to receive
      either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine
      0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at
      10 ml h-1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The
      primary outcome measure was area under the curve of the pain verbal rating score
      whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid
      consumption at 24 h. RESULTS: AUC moving was mean (SD) 71 (34) mm h-1vs 58 (41)
      vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was
      also significantly lower in patients receiving both. The total 24 h opioid
      consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4.
      No adverse events were observed. CONCLUSIONS: The combination of both pre
      incisional PECs blocks and postoperative LA infusion provides better analgesia
      over 24 h than either technique alone after non-ambulatory breast-cancer surgery.
      CLINICAL TRIAL REGISTRATION: NCT 03024697.

PMID- 29576126
TI  - Investigation into the visual perceptive ability of anaesthetists during
      ultrasound-guided interscalene and femoral blocks conducted on soft embalmed
      cadavers: a randomised single-blind study.
AB  - BACKGROUND: Errors may occur during regional anaesthesia whilst searching for
      nerves, needle tips, and test doses. Poor visual search impacts on decision
      making, clinical intervention, and patient safety. METHODS: We conducted a
      randomised single-blind study in a single university hospital. Twenty trainees
      and two consultants examined the paired B-mode and fused B-mode and elastography
      video recordings of 24 interscalene and 24 femoral blocks conducted on two soft
      embalmed cadavers. Perineural injection was randomised equally to 0.25, 0.5, and
      1.0 ml volumes. Tissue displacement perceived on both imaging modalities was
      defined as 'target' or 'distractor'. Our primary objective was to test the
      anaesthetists' perception of the number and proportion of targets and distractors
      on B-mode and fused elastography videos collected during femoral and sciatic
      nerve block on soft embalmed cadavers. Our secondary objectives were to determine
      the differences between novices and experts, and between test-dose volumes, and
      to measure the area and brightness of spread and strain patterns. RESULTS: All
      anaesthetists recognised perineural spread using 0.25 ml volumes. Distractor
      patterns were recognised in 133 (12%) of B-mode and in 403 (38%) of fused B-mode
      and elastography patterns; P<0.001. With elastography, novice recognition
      improved from 12 to 37% (P<0.001), and consultant recognition increased from 24
      to 53%; P<0.001. Distractor recognition improved from 8 to 31% using 0.25 ml
      volumes (P<0.001), and from 15 to 45% using 1 ml volumes (P<0.001). CONCLUSIONS:
      Visual search improved with fusion elastography, increased volume, and
      consultants. A need exists to investigate image search strategies.

PMID- 29576127
TI  - Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP
      step method.
AB  - BACKGROUND: Postoperative pulmonary complications are common. Between patients
      there are differences in lung and chest wall mechanics. Individualised mechanical
      ventilation based on measurement of transpulmonary pressures would be a step
      forward. A previously described method evaluates lung and chest wall mechanics
      from a change of DeltaPEEP and calculation of change in end-expiratory lung
      volume (DeltaEELV). The aim of the present study was to validate this PEEP-step
      method (PSM) during general anaesthesia by comparing it with the conventional
      method using oesophageal pressure (PES) measurements. METHODS: In 24 lung healthy
      subjects (BMI 18.5-32), three different sizes of PEEP steps were performed during
      general anaesthesia and DeltaEELVs were calculated. Transpulmonary driving
      pressure (DeltaPL) for a tidal volume equal to each DeltaEELV was measured using
      PES measurements and compared to DeltaPEEP with limits of agreement and
      intraclass correlation coefficients (ICC). DeltaPL calculated with both methods
      was compared with a Bland-Altman plot. RESULTS: Mean differences between
      DeltaPEEP and DeltaPL were <0.15 cm H2O, 95% limits of agreements -2.1 to 2.0 cm
      H2O, ICC 0.6-0.83. Mean differences between DeltaPL calculated by both methods
      were <0.2 cm H2O. Ratio of lung elastance and respiratory system elastance was
      0.5-0.95. CONCLUSIONS: The large variation in mechanical properties among the
      lung healthy patients stresses the need for individualised ventilator settings
      based on measurements of lung and chest wall mechanics. The agreement between
      DeltaPLs measured by the two methods during general anaesthesia suggests the use
      of the non-invasive PSM in this patient population. CLINICAL TRIAL REGISTRATION:
      NCT 02830516.

PMID- 29576128
TI  - Non-invasive positive-pressure ventilation with positive end-expiratory pressure
      counteracts inward air leaks during preoxygenation: a randomised crossover
      controlled study in healthy volunteers.
AB  - BACKGROUND: During preoxygenation, the lack of tight fit between the mask and the
      patient's face results in inward air leak preventing effective preoxygenation. We
      hypothesized that non-invasive positive-pressure ventilation and positive end
      expiratory pressure (PEEP) could counteract inward air leak. METHODS: Healthy
      volunteers were randomly assigned to preoxygenated through spontaneous breathing
      without leak (SB), spontaneous breathing with a calibrated air leak (T-shaped
      piece between the mouth and the breathing system; SB-leak), or non-invasive
      positive inspiratory pressure ventilation (inspiratory support +6 cm H2O; PEEP +5
      cm H2O) with calibrated leak (PPV-leak). The volunteers breathed through a
      mouthpiece connected to an anaesthesia ventilator. The expired oxygen fraction
      (FeO2) and air-leak flow (ml s-1) were measured. The primary end point was the
      proportion of volunteers with FeO2 >90% at 3 min. The secondary end points were
      FeO2 at 3 min, time to reach FeO2 of 90%, and the inspiratory air-leak flow.
      RESULTS: Twenty healthy volunteers were included. The proportion of volunteers
      with FeO2 >90% at 3 min was 0% in the SB-leak group, 95% in the SB group, and
      100% in the PPV-leak group (P<0.001). At 3 min, the mean [standard deviation
      (sd)] FeO2 was 89 (1)%, 76 (1)%, and 90 (0)% in the SB, SB-leak, and PPV-leak
      groups, respectively (P<0.001). The mean (sd) inward air leak was 59 (12) ml s-1
      in the SB-leak group, but 0 (0) ml s-1 in the PPV-leak group (P<0.001).
      CONCLUSIONS: Preoxygenation through non-invasive positive-pressure ventilation
      and PEEP provided effective preoxygenation despite an inward air leak. CLINICAL
      TRIAL REGISTRATION: NCT03087825.

PMID- 29576129
TI  - Comments on 'An overview of space medicine'.

PMID- 29576131
TI  - Comments on: Thiopental to desflurane-an anaesthetic journey. Where are we going
      next?

PMID- 29576130
TI  - Authors' response to: 'Comments on "An overview of space medicine"'.

PMID- 29576132
TI  - Response to Serrao and Goodchild.

PMID- 29576133
TI  - Most patients undergoing phaeochromocytoma removal could be safely discharged
      from the post-anaesthesia care unit to the ward after three hours monitoring.

PMID- 29576134
TI  - Paediatric anaphylaxis management: training staff to draw up the correct dose of
      epinephrine.

PMID- 29576136
TI  - Informed consent in anaesthesia.

PMID- 29576135
TI  - Ultrasound detection of free-floating thrombus during internal jugular vein
      catheterisation.

PMID- 29576138
TI  - Discussion.

PMID- 29576137
TI  - Epiglottis folding double with supraglottic airway devices.

PMID- 29576139
TI  - Discussion.

PMID- 29576140
TI  - Discussion.

PMID- 29576141
TI  - Discussion.

PMID- 29576142
TI  - Discussion.

PMID- 29576143
TI  - Discussion.

PMID- 29576144
TI  - Discussion.

PMID- 29576145
TI  - Discussion.

PMID- 29576146
TI  - Discussion.

PMID- 29576147
TI  - Discussion.

PMID- 29576148
TI  - Discussion.

PMID- 29576149
TI  - Discussion.

PMID- 29576150
TI  - Discussion.

PMID- 29576151
TI  - Discussion.

PMID- 29576152
TI  - Discussion.

PMID- 29576153
TI  - Discussion.

PMID- 29576154
TI  - Discussion.

PMID- 29576155
TI  - Discussion.

PMID- 29576156
TI  - Discussion.

PMID- 29576157
TI  - Discussion.

PMID- 29576158
TI  - Discussion.

PMID- 29576159
TI  - Discussion.

PMID- 29576160
TI  - Discussion.

PMID- 29576161
TI  - Discussion.

PMID- 29576162
TI  - Discussion.

PMID- 29576163
TI  - Discussion.

PMID- 29576164
TI  - Discussion.

PMID- 29576165
TI  - Discussion.

PMID- 29576166
TI  - Discussion.

PMID- 29576167
TI  - Discussion.

PMID- 29576168
TI  - Discussion.

PMID- 29576169
TI  - Discussion.

PMID- 29576170
TI  - Discussion.

PMID- 29576171
TI  - Discussion.

PMID- 29576172
TI  - April 2018 Featured Articles, Volume 226.

PMID- 29576173
TI  - Does longer breastfeeding duration decrease the risk of asthma?

PMID- 29576175
TI  - 50 Years Ago in The Journal of Pediatrics: The Effect of Pretreatment with
      Pentobarbital, Meperidine, or Hyperbaric Oxygen on the Response to Anoxia and
      Resuscitation in Newborn Rabbits.

PMID- 29576176
TI  - Diagnostic pathways need validation across varied healthcare settings.

PMID- 29576177
TI  - Cystic periventricular leukomalacia: now you see it, now you don't?

PMID- 29576174
TI  - Advances in Juvenile Dermatomyositis: Myositis Specific Antibodies Aid in
      Understanding Disease Heterogeneity.

PMID- 29576178
TI  - 50 Years Ago in The Journal of Pediatrics: A Search for the Reservoir of
      Cytomegalovirus in Salivary Gland Tissue.

PMID- 29576179
TI  - Revisiting the use of probiotics in premature infants for the prevention of NEC.

PMID- 29576180
TI  - The incidental detection of alpha thalassemia.

PMID- 29576181
TI  - Increased prescription drug use immediately after childhood cancer.

PMID- 29576182
TI  - Application of Assessment Metrics for an Academic Department Faculty Development
      Program.

PMID- 29576183
TI  - 50 Years Ago in The Journal of Pediatrics: Variability in the Manifestations of
      Phenylketonuria/Transient Hyperphenylalaninemia.

PMID- 29576184
TI  - Reply.

PMID- 29576185
TI  - Reply.

PMID- 29576186
TI  - Update on the Treatment of molluscum Contagiosum in children.
AB  - Molluscum contagiosum is one of the most common viral infections in childhood. It
      is a benign and usually self-limiting infection, but its treatment in children
      can be challenging, particularly when the patient presents multiple lesions or
      when lesions are symptomatic or highly visible. Several treatment options exist.
      Choice of treatment depends on the number and location of lesions, the prior
      experience of the treating physician, and the preferences of the child's parents
      or carers. This article provides an update on treatment options for molluscum
      contagiosum, with a particular focus on immunocompetent pediatric patients.

PMID- 29576187
TI  - Allergic Contact Dermatitis Due to Chlorhexidine in 2 Pediatric Patients.

PMID- 29576188
TI  - Cross-Cultural Adaptation to Spanish of the Hair Specific Skindex-29 Scale: A
      Valuable Tool for Our Clinical Practice.

PMID- 29576189
TI  - Alopecia Areata and Palmoplantar Pustulosis: Report of 4 Cases.

PMID- 29576190
TI  - Conference Report: Psychiatric Genomics Consortium Meeting: Pathways to Drugs,
      London, March 2017.

PMID- 29576191
TI  - Impact of Prenatal Stress on Offspring Psychopathology and Comorbidity With
      General Medicine Later in Life.

PMID- 29576192
TI  - Improved Cardiovascular Risk Factors Control Associated with a Large-Scale
      Population Management Program Among Diabetes Patients.
AB  - BACKGROUND: Optimal cardiovascular risk factors control among individuals with
      diabetes remains a challenge. We evaluated changes in glucose, lipid, and blood
      pressure control among diabetes patients after implementation of a large-scale
      population management program, known as Preventing Heart Attacks and Strokes
      Everyday, at Kaiser Permanente Northern California (KPNC), during 2004-2013.
      METHODS: We used National Committee for Quality Assurance Healthcare
      Effectiveness Data and Information Set cut points to identify prevalence of poor
      glycemic (hemoglobin A1c > 9%) control, good lipid control (low-density
      lipoprotein cholesterol < 100 mg/dL), and good blood pressure control (blood
      pressure < 140/90 mm Hg) in each year (N range = 98,345 to 122,177 over the
      entire period). We assessed trends in risk factor control based on Joinpoint
      regression and average annual percentage change (AAPC) compared with published
      National Committee for Quality Assurance Healthcare Effectiveness Data and
      Information Set commercial rates. RESULTS: We found that the prevalence of poor
      glycemic control (hemoglobin A1c > 9%) declined in both KPNC and nationally, but
      was statistically significant only in KPNC (AAPC = -4.8; P < .05). The prevalence
      of good lipid control (low-density lipoprotein cholesterol < 100 mg/dL) increased
      significantly in KPNC (47% to 71%; AAPC = +4.3; P < .05), but there was no
      significant improvement nationally (40% to 44%; AAPC = +1.4; P = .2). The
      prevalence of blood pressure control (<140/90 mm Hg) was higher in KPNC (77% to
      82%; AAPC = +1.1; P < .05) versus nationally (57% to 62%; AAPC = +1.9; P < .05)
      during the reported years 2007-2013. CONCLUSIONS: Relative to national
      benchmarks, a substantially greater improvement in risk factor control among
      adults with diabetes was observed after implementation of a comprehensive
      population management program.

PMID- 29576193
TI  - Role of Salt Valency in the Switch of H-NS Proteins between DNA-Bridging and DNA
      Stiffening Modes.
AB  - This work investigates the interactions of H-NS proteins and bacterial genomic
      DNA through computer simulations performed with a coarse-grained model. The model
      was developed specifically to study the switch of H-NS proteins from the DNA
      stiffening to the DNA-bridging mode, which has been observed repeatedly upon
      addition of multivalent cations to the buffer but is still not understood.
      Unraveling the corresponding mechanism is all the more crucial, as the regulation
      properties of H-NS proteins, as well as other nucleoid proteins, are linked to
      their DNA-binding properties. The simulations reported here support a mechanism,
      according to which the primary role of multivalent cations consists in decreasing
      the strength of H-NS/DNA interactions compared to H-NS/H-NS interactions, with
      the latter ones becoming energetically favored with respect to the former ones
      above a certain threshold of the effective valency of the cations of the buffer.
      Below the threshold, H-NS dimers form filaments, which stretch along the DNA
      molecule but are quite inefficient in bridging genomically distant DNA sites (DNA
      stiffening mode). In contrast, just above the threshold, H-NS dimers form three
      dimensional clusters, which are able to connect DNA sites that are distant from
      the genomic point of view (DNA-bridging mode). The model provides clear
      rationales for the experimental observations that the switch between the two
      modes is a threshold effect and that the ability of H-NS dimers to form higher
      order oligomers is crucial for their bridging capabilities.

PMID- 29576194
TI  - Laparoscopic nephroureterectomy with laser endoscopic transuretral disinsertion
      in lateral decubitus: progressive adaptation to retroperitoneocopic approach.
AB  - BACKGROUND: The ureteral disinsertion with bladder cuff technique continues to
      evolve. We present the endoscopic laser transurethral technique combined with a
      transperitoneal and retroperitoneal laparoscopic approach in lateral decubitus,
      without patient repositioning, for treating urothelial carcinomas of the upper
      urinary tract. MATERIALS AND METHODS: We present 3 laparoscopic
      nephroureterectomies: 1 transperitoneal and 2 retroperitoneal. Disinsertion was
      performed in lateral decubitus using a flexible cystoscope and a 365-MUm holmium
      laser fiber. The endoscopic technique was progressively adapted to 3-port and
      single-port retroperitoneoscopic approaches. Before laparoscopic handling of the
      kidney, ureter was clamped below the tumour. The endoscopic technique was then
      started. Both approaches were simultaneously employed. RESULTS:
      Nephroureterectomies were achieved performing en bloc endoscopic disinsertion of
      the bladder cuff and ensuring a closed system comparable to open technique. The
      second case required reconversion due to technical problems and extension of the
      surgical time. No relapses were diagnosed during follow-up. CONCLUSION: Results
      are comparable to open surgery, technique ensured compliance to oncology
      principles, enabled disinsertion in lateral decubitus and avoid patient
      repositioning saving surgical time. The results reflect the benefits of minimally
      invasive surgery in all cases.

PMID- 29576195
TI  - [The Script Concordance Test: A multimodal teaching tool].
AB  - In recent years, there has been a major interest in assessing learners during
      their medical education. The core of medical competence is the clinical reasoning
      that should be acquired by all medical actors. Its assessment includes the
      ability to integrate and apply different types of knowledge, weigh critical
      evidence and think about the process used to have a diagnosis. French faculties
      of medicine will have to include it in the training and evaluation of students
      during 2017. It should therefore be part of the new docimological modalities of
      the computerized "Epreuves Classantes Nationales" from 2020 onwards. In this
      article, we did a specific review of the literature concerning the theoretical
      foundations, methodology and use of Script Concordance Test (SCT) in the field of
      health. To do so, we used the PubMed, EMBASE and PsycINFO databases and selected
      articles in English and French language using the following keywords alone or in
      combination: script, concordance, script concordance test, medical studies,
      validity, fidelity, psychometric properties. We have found 62 articles that
      matched our search. Built on a well-targeted methodology, the SCT is a reliable
      and valid pedagogical tool. It can discriminate the levels of practice between
      medical students, residents and medical doctors, evaluate the progression and
      skills of clinical reasoning. It can be administered online, in multicentric
      centers, at a national or international level. There are, however, limitations
      that teachers must take into account.

PMID- 29576196
TI  - [Recurrent abdominal pain in an 88-year-old woman].

PMID- 29576197
TI  - [The nocebo effect: Various aspects and consequences in clinical practice].

PMID- 29576198
TI  - Tracheal Leiomyosarcoma: Urgent Bronchoscopic Treatment of an Acute Ventilatory
      Failure.

PMID- 29576199
TI  - Obstructive Sleep Apnea Syndrome and chronic obstructive pulmonary disease:
      Overlap or Syndrome.

PMID- 29576200
TI  - Spontaneous Pulmonary Hematoma as a Complication of Anticoagulant Therapy.

PMID- 29576201
TI  - Micellar HPLC method for the simultaneous determination of three anticonvulsant
      drugs in dosage forms and biological fluids. Application to dissolution-rate
      testing.
AB  - This work describes a micellar liquid chromatographic method which was developed
      and validated to determine simultaneously three structurally-related
      antiepileptic drugs; namely carbamazepine (CMZ), oxcarbazepine (OCZ) and
      eslicarbazepine acetate (ECZ). The analysis was achieved using a phenyl column
      (250mm*4.6mm i.d., 5MUm particle size), a mobile phase consisting of a mixture of
      0.3% triethylamine and 10% n-butanol in a solution of 0.05M sodium dodecyl
      sulphate adjusted to pH 7.0 using 0.02M orthophosphoric acid. The mobile phase
      was pumped at a flow rate of 1.5mLmin-1 and detection was adjusted at 215nm. The
      method showed good linearity (r2>0.998) over the concentration ranges of 0.1-10
      for CMZ and OCZ and 0.2-20MUgmL-1 for ECZ. The suggested method was successfully
      applied for the analysis of the studied drugs in their dosage forms and for the
      determination of CMZ and OCZ in spiked human urine and plasma without prior
      extraction. The proposed method was further extended to the analysis of real
      samples of plasma and urine of volunteers receiving therapy of CMZ and OCZ.
      Furthermore, the method was successfully applied to tablets dissolution-rate
      testing, and the results were satisfactory.

PMID- 29576202
TI  - Island cartilage vs temporalis fascia in type 1 tympanoplasty: A prospective
      study.
AB  - OBJECTIVE: (1) To compare the results of graft take-up and audiological outcome
      of temporalis fascia versus island cartilage graft in type 1 tympanoplasty. (2)
      To compare the rate of postoperative retraction of neotympanum in both. METHODS:
      A prospective study was conducted on 70 patients of ages ranging from 11 to 50
      years with dry subtotal perforation. 35 underwent island cartilage tympanoplasty
      and 35 underwent type 1 tympanoplasty using temporalis fascia graft. Graft
      acceptance rates and post-operative audiograms were compared. RESULTS: At one
      year follow up, the graft take-up rate for temporalis fascia and island cartilage
      graft were found to be 82.9% and 97.1% respectively, which was found to be
      statistically significant (p<0.05). In the temporalis fascia group, two out of 35
      patients (5.7%) had retraction of the neo tympanum. There was no incidence of
      retraction using island cartilage graft. There was no significant difference in
      the postoperative air-bone gap gain between temporalis fascia graft and island
      cartilage graft. CONCLUSION: Island cartilage tympanoplasty shows a high degree
      of reliability in high risk cases. It has a higher graft take-up rate with no
      incidence of retraction of neotympanum. Moreover, it provided significant hearing
      improvement in our patients.

PMID- 29576203
TI  - ?

PMID- 29576204
TI  - [The image and status of the child over the centuries].
AB  - Children have not always held the privileged position within the family that they
      enjoy today. In the predominantly rural society of the past, they belonged as
      much to a lineage as they did to their parents. The frailty of life was such that
      the need to carry on the line of descent overrode any other considerations. From
      the 18th century, a new concept of the family appeared, in which the child, more
      autonomous, became an object of attention and affection.

PMID- 29576205
TI  - [The evolution of places of birth].
AB  - Since the beginning of the 19th century, medical advances have drastically cut
      the number of deaths at birth, ensuring a maximum level of safety of childbirth
      today. However, there is increasing demand for alternative forms of childbirth
      which take into account more the expectations of the future parents as well as
      the psychological and relational dimensions. The current experimentation
      involving birth centres could lead the way for the development of such
      possibilities from 2018.

PMID- 29576206
TI  - [The challenges of preparing for birth and parenthood].
AB  - Pregnancy and the birth of a child represents, for the new parents, a radical
      change in their lives. Access to parenthood involves a physical and psychological
      reorganisation which requires support. Preparation for birth and parenthood aims
      to help young parents along this pathway, in order to let them discover their own
      potential.

PMID- 29576207
TI  - [Support and tools for preparing for birth].
AB  - There are a thousand and one ways of preparing to be a parent. Specific support
      is offered to pregnant women or the couple in order to take the time to prepare
      for this personal transformation. Haptonomy, sophrology, shiatsu and massage,
      acupuncture or gestalt therapy are some of the methods helping parents to prepare
      to welcome their future child with peace of mind.

PMID- 29576208
TI  - [Newborn care in the delivery room].
AB  - The arrival of a newborn in the delivery room is a precious and unique moment
      which caregivers support by seeing to the comfort and wellbeing of the baby and
      his or her parents. Developmental care is introduced early, skin-to-skin contact
      is favoured and invasive treatment is only performed if strictly necessary. At
      the same time, the teams are ready to intervene in the event of a complication.

PMID- 29576209
TI  - [Intervention and role of the paediatrician in the delivery room].
AB  - Some newborns require the presence of a paediatrician in the delivery room, for
      emergency care. This generally leads to hospitalisation in neonatal intensive
      care or neonatology. Prematurity and respiratory distress are the main causes.
      These unexpected situations are a source of anxiety for the parents. It is
      essential that the multidisciplinary team draws on both its technical and
      relational expertise, in order to provide optimal treatment to the infant while
      supporting the parents with the necessary empathy.

PMID- 29576211
TI  - [Homebirth, a choice to support].
AB  - There are relatively few homebirths in France. They represent around 1% of
      births. However, more and more women and couples are demanding this choice.
      Jacqueline Lavillonniere, a midwife for 40 years, practises homebirths. Here, she
      describes her career and her particular practice in tune with the physiology of
      birth.

PMID- 29576210
TI  - ["We gave birth in a birth centre."]
AB  - Alice and Julien chose a birth centre for the birth of their baby. They share
      their experience of the first appointments, the preparation for the birth and the
      delivery which took place in accordance with their choices and at their pace.

PMID- 29576212
TI  - [Mother-baby follow-up at home and the welcome of the baby in the family].
AB  - Upon discharge from the maternity hospital, the newborn is welcomed not only in a
      home but also within a family. The postnatal follow-up over the first few weeks
      can take several forms: a programme to support the return home, hospital at home
      service or follow-up by a private practice midwife or professionals from the
      mother and infant welfare protection service. The aim is to meet the needs of the
      baby, favour the establishment of the parent-baby bond and to support the
      construction of parenthood.

PMID- 29576213
TI  - [Childbirth support by children's nurses from the mother and baby welfare
      protection service].
AB  - As the stay in maternity hospitals gets shorter, parents often feel helpless upon
      their return home. It is therefore necessary to identify resource professionals
      to help them on the continuation of the care pathway. The children's nurses from
      the mother and infant welfare protection service, a frontline service accessible
      to everyone, provide their expertise to meet the basic needs of the child and
      support the parents in the development of their skills.

PMID- 29576214
TI  - ?

PMID- 29576216
TI  - ?

PMID- 29576215
TI  - [Creation of an observation scale for newborns in the maternity setting].
AB  - In clinical practice in the maternity setting, professionals are regularly
      confronted with situations for which a clinical observation of the newborn's
      condition is necessary. The Assessment for Newborn Development and Abilities
      (Panda) scale is a tool for evaluating the sensory-motor skills of newborns and
      their relationship with others, as well as raising professionals' awareness of
      their fine observation.

PMID- 29576217
TI  - Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA
      Synthetase, Cause a Hypomyelinating Leukodystrophy.
AB  - Hypomyelinating leukodystrophies are genetic disorders characterized by
      insufficient myelin deposition during development. They are diagnosed on the
      basis of both clinical and MRI features followed by genetic confirmation. Here,
      we report on four unrelated affected individuals with hypomyelination and bi
      allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl
      prolyl-aminoacyl-tRNA synthetase. EPRS is a bifunctional aminoacyl-tRNA
      synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA
      species. It is a subunit of a large multisynthetase complex composed of eight
      aminoacyl-tRNA synthetases and its three interacting proteins. In total, five
      different EPRS mutations were identified. The p.Pro1115Arg variation did not
      affect the assembly of the multisynthetase complex (MSC) as monitored by affinity
      purification-mass spectrometry. However, immunoblot analyses on protein extracts
      from fibroblasts of the two affected individuals sharing the p.Pro1115Arg variant
      showed reduced EPRS amounts. EPRS activity was reduced in one affected
      individual's lymphoblasts and in a purified recombinant protein model.
      Interestingly, two other cytoplasmic aminoacyl-tRNA synthetases have previously
      been implicated in hypomyelinating leukodystrophies bearing clinical and
      radiological similarities to those in the individuals we studied. We therefore
      hypothesized that leukodystrophies caused by mutations in genes encoding
      cytoplasmic aminoacyl-tRNA synthetases share a common underlying mechanism, such
      as reduced protein availability, abnormal assembly of the multisynthetase
      complex, and/or abnormal aminoacylation, all resulting in reduced translation
      capacity and insufficient myelin deposition in the developing brain.

PMID- 29576218
TI  - Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial
      Presequence Protease Cause Neurodegeneration in Early Childhood.
AB  - Mitochondrial disorders causing neurodegeneration in childhood are genetically
      heterogeneous, and the underlying genetic etiology remains unknown in many
      affected individuals. We identified biallelic variants in PMPCB in individuals of
      four families including one family with two affected siblings with
      neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of
      the essential mitochondrial processing protease (MPP), which is required for
      maturation of the majority of mitochondrial precursor proteins. Mitochondria
      isolated from two fibroblast cell lines and induced pluripotent stem cells
      derived from one affected individual and differentiated neuroepithelial stem
      cells showed reduced PMPCB levels and accumulation of the processing intermediate
      of frataxin, a sensitive substrate for MPP dysfunction. Introduction of the
      identified PMPCB variants into the homologous S. cerevisiae Mas1 protein resulted
      in a severe growth and MPP processing defect leading to the accumulation of
      mitochondrial precursor proteins and early impairment of the biogenesis of iron
      sulfur clusters, which are indispensable for a broad range of crucial cellular
      functions. Analysis of biopsy materials of an affected individual revealed
      changes and decreased activity in iron-sulfur cluster-containing respiratory
      chain complexes and dysfunction of mitochondrial and cytosolic Fe-S cluster
      dependent enzymes. We conclude that biallelic mutations in PMPCB cause defects in
      MPP proteolytic activity leading to dysregulation of iron-sulfur cluster
      biogenesis and triggering a complex neurological phenotype of neurodegeneration
      in early childhood.

PMID- 29576219
TI  - Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause
      Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex
      Deficiencies.
AB  - Biogenesis of the mitochondrial oxidative phosphorylation system, which produces
      the bulk of ATP for almost all eukaryotic cells, depends on the translation of 13
      mtDNA-encoded polypeptides by mitochondria-specific ribosomes in the
      mitochondrial matrix. These mitoribosomes are dual-origin ribonucleoprotein
      complexes, which contain mtDNA-encoded rRNAs and tRNAs and ~80 nucleus-encoded
      proteins. An increasing number of gene mutations that impair mitoribosomal
      function and result in multiple OXPHOS deficiencies are being linked to human
      mitochondrial diseases. Using exome sequencing in two unrelated subjects
      presenting with sensorineural hearing impairment, mild developmental delay,
      hypoglycemia, and a combined OXPHOS deficiency, we identified mutations in the
      gene encoding the mitochondrial ribosomal protein S2, which has not previously
      been implicated in disease. Characterization of subjects' fibroblasts revealed a
      decrease in the steady-state amounts of mutant MRPS2, and this decrease was shown
      by complexome profiling to prevent the assembly of the small mitoribosomal
      subunit. In turn, mitochondrial translation was inhibited, resulting in a
      combined OXPHOS deficiency detectable in subjects' muscle and liver biopsies as
      well as in cultured skin fibroblasts. Reintroduction of wild-type MRPS2 restored
      mitochondrial translation and OXPHOS assembly. The combination of lactic
      acidemia, hypoglycemia, and sensorineural hearing loss, especially in the
      presence of a combined OXPHOS deficiency, should raise suspicion for a ribosomal
      subunit-related mitochondrial defect, and clinical recognition could allow for a
      targeted diagnostic approach. The identification of MRPS2 as an additional gene
      related to mitochondrial disease further expands the genetic and phenotypic
      spectra of OXPHOS deficiencies caused by impaired mitochondrial translation.

PMID- 29576220
TI  - Fusion of Three-Dimensional Echocardiographic Regional Myocardial Strain with
      Cardiac Computed Tomography for Noninvasive Evaluation of the Hemodynamic Impact
      of Coronary Stenosis in Patients with Chest Pain.
AB  - BACKGROUND: Combined evaluation of coronary stenosis and the extent of ischemia
      is essential in patients with chest pain. Intermediate-grade stenosis on computed
      tomographic coronary angiography (CTCA) frequently triggers downstream nuclear
      stress testing. Alternative approaches without stress and/or radiation may have
      important implications. Myocardial strain measured from echocardiographic images
      can be used to detect subclinical dysfunction. The authors recently tested the
      feasibility of fusion of three-dimensional (3D) echocardiography-derived regional
      resting longitudinal strain with coronary arteries from CTCA to determine the
      hemodynamic significance of stenosis. The aim of the present study was to
      validate this approach against accepted reference techniques. METHODS: Seventy
      eight patients with chest pain referred for CTCA who also underwent 3D
      echocardiography and regadenoson stress computed tomography were prospectively
      studied. Left ventricular longitudinal strain data (TomTec) were used to generate
      fused 3D displays and detect resting strain abnormalities (RSAs) in each coronary
      territory. Computed tomographic coronary angiographic images were interpreted for
      the presence and severity of stenosis. Fused 3D displays of subendocardial x-ray
      attenuation were created to detect stress perfusion defects (SPDs). In patients
      with stenosis >25% in at least one artery, fractional flow reserve was quantified
      (HeartFlow). RSA as a marker of significant stenosis was validated against two
      different combined references: stenosis >50% on CTCA and SPDs seen in the same
      territory (reference standard A) and fractional flow reserve < 0.80 and SPDs in
      the same territory (reference standard B). RESULTS: Of the 99 arteries with no
      stenosis >50% and no SPDs, considered as normal, 19 (19%) had RSAs. Conversely,
      with stenosis >50% and SPDs, RSAs were considerably more frequent (17 of 24
      [71%]). The sensitivity, specificity, and accuracy of RSA were 0.71, 0.81, and
      0.79, respectively, against reference standard A and 0.83, 0.81, and 0.82 against
      reference standard B. CONCLUSIONS: Fusion of CTCA and 3D echocardiography-derived
      resting myocardial strain provides combined displays, which may be useful in
      determination of the hemodynamic or functional impact of coronary abnormalities,
      without additional ionizing radiation or stress testing.

PMID- 29576221
TI  - [Desmoplastic small round cell tumor in children, adolescents and young adults].
AB  - Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma that typically
      affects pediatric and young adult patients with a median age in the general and
      in the pediatric population of 24.6 years (range 4-58 years) and 15.0 years
      (range 0-21 years) respectively, with a strong male predominance. This tumor is
      characterized by a specific t(11;22)(p13;q12) that results in fusion of EWS and
      WT1 genes which can be demonstrated by RT-PCR or by FISH. DSRCT most frequently
      presents as an intra-abdominal primary mass associated with peritoneal seeding
      and a highly aggressive pattern of spread. Generally, all tumors showed the
      typical histologic findings of variably sized clusters of poly-phenotypic small,
      round, or spindled cells lying in a desmoplastic stroma. Treatment of this
      malignancy remains a challenge. The combination of polychemotherapy regimens and
      aggressive surgery followed by whole abdomen radiation therapy represents
      nowadays a classical protocol for DSRCT. The survival rate of DSRCT patients is
      still disappointing around 20 %. However, the survival of patients who had
      complete resection of the tumor appears better. Hopes are turning to targeted
      therapeutics against this simple genomic sarcoma. Authors summarize medical
      knowledge of this rare tumor.

PMID- 29576222
TI  - Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes
      in HBV-related hepatocellular carcinoma.
AB  - BACKGROUND: The immunosuppression of tumor-infiltrating lymphocytes (TILs) is
      associated with rapid progression of hepatitis B virus-related hepatocellular
      carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3)
      and programmed cell death 1 (PD-1) are important inhibitory molecules expressed
      on the surface of T cells, but their roles in the function of TILs in HBV-HCC are
      poorly understood. We aimed to study the roles of these two markers in HBV-HCC.
      METHODS: Ninety patients with pathologically confirmed HBV-associated HCC were
      enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent
      tissues were collected, and isolating peripheral blood mononuclear cells, TILs
      and adjacent-infiltrating lymphocytes were isolated from these samples. The
      patients were followed-up to allow survival analysis. RESULTS: Tim-3 or/and PD-1
      was up-regulated expressed on CD4+ and CD8+ TILs in HBV-HCC patients and a higher
      proportion of TILs expressed PD-1 alone. Tim-3+ and PD-1+ TILs greatly decreased
      secretion of IFN-? and TNF-a. Expression of Tim-3 and PD-1 on TILs negatively
      correlated with disease-free survival of HCC patients. Direct blockade of Tim-3
      and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN
      ? and TNF-a. CONCLUSION: Expression of Tim-3 and/or PD-1 on TILs impairs their
      function and correlates negatively with disease-free survival in HBV-HCC. Direct
      blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a
      potential target for novel immunotherapy in HBV-HCC.

PMID- 29576223
TI  - Gadolinium-based relative contrast enhancement in primary sclerosing cholangitis:
      additional benefit for clinicians?
AB  - AIM: To evaluate the benefit of extracellular gadolinium-based contrast agent
      (GBCA) enhanced magnetic resonance imaging (MRI) in addition to conventional non
      enhanced T2-weighted imaging (WI) for quantification of inflammatory or fibrotic
      alterations in the liver parenchyma of patients with primary sclerosing
      cholangitis (PSC). MATERIAL AND METHODS: MRI (3 T) examinations were reviewed
      retrospectively by two radiologists in 27 PSC patients (age 42.9+/-15.6 years),
      and 19 controls. Regions of interest (ROIs) were drawn onto T2 hyperintense and
      T2 isointense areas and copied to section position matched non-enhanced and
      delayed-phase contrast-enhanced T1WI. Signal intensities (SI) obtained from ROIs
      of the multiphase T1WI were used to calculate relative liver enhancement (RLE).
      The interobserver agreement of RLE and quantified T2 signal was calculated using
      Bland-Altman analysis. RLE assessed for both T2 hyperintense (RLEhyper) and T2
      isointense (RLEiso) areas were compared in patients and controls (RLEhealthy).
      RESULTS: The interobserver agreement of RLE in affected hyperintense areas (bias 
      0.77, limits of agreement -51.7 to 50.1) was superior to the quantification of T2
      signal only in these areas (bias -3.35, limits of agreement -162.4 to 155.7). The
      RLEhyper (86.2+/-9.7%) was higher than the RLEiso (59.8+/-6.2%, p=0.03) and the
      RLEhealthy (53.2+/-2.7%, p=0.002). The mean RLEiso was not significantly
      different from the RLEhealthy (p=0.3). CONCLUSION: The extracellular gadolinium
      based RLE of T2 hyperintense areas could be a useful add-on for routine follow up
      MRI in the detection of early inflammatory changes, possibly preceding formation
      of fibrotic scarring in PSC patients, if validated in larger cohorts.

PMID- 29576224
TI  - MDCT in suspected lumbar spine fracture: comparison of standard and reduced dose
      settings using iterative reconstruction.
AB  - AIM: To compare standard (SD-) and reduced-dose computed tomography (RD-CT) in
      combination with iterative reconstruction (IR) in emergency patients with
      suspected lumbar spine fracture. MATERIAL AND METHODS: Forty emergency patients
      with suspected lumbar spinal disorder who underwent RD-CT and 40 body mass index
      matched patients undergoing SD-CT were enrolled in this retrospective study. Raw
      data for RD-CT were reconstructed using two increasing IR levels (IRL) 4 and 6,
      while SD-CT was reconstructed with IRL3. Two radiologists assessed image quality,
      image noise, and reader confidence in interpreting findings of spinal fractures
      in a blinded manner. RESULTS: Effective radiation dose was reduced by 50% using
      RD-CT. Overall subjective image quality (SIQ) was high for both protocols and
      slightly superior in the RD-CT protocol for both IRL compared to SD-CT. The
      detection rate of spinal disorders was high for both protocols with a high
      interobserver agreement. CONCLUSION: RD-CT with higher levels of IR results in
      substantial dose reduction of 50% in lumbar spine CT while maintaining an
      excellent subjective image quality resulting in a high diagnostic confidence.

PMID- 29576225
TI  - Single-lung ventilation with bronchofibroscopy during lung resection surgery.
AB  - Lung isolation using one-lung ventilation is common during thoracic surgery
      procedures, as it allows proper visualisation and manipulation of the lung to be
      operated on. Selective lobar blockade has been described in patients that do not
      tolerate one-lung ventilation, and is usually achieved using endobronchial
      blockers. However, it depends on endobronchial blocker availability, its
      complexity regarding proper positioning, and the need for constant monitoring to
      ensure the correct placement of the bronchial seal. In the clinical case to be
      described, a new method was used to increase the available surface for oxygen
      exchange. This was accomplished by means of direct supply of oxygen through the
      bronchoscope's working channel to one of the not-to-be operated-on, non
      ventilated lung lobes. With this technique, the surgeon had an optimal operating
      field, oxygenation from one-lung ventilation improved and no perioperative
      complications were found.

PMID- 29576226
TI  - Reply to: "Exercise oximetry in patients with arterial claudication".

PMID- 29576227
TI  - Effects of early comprehensive interventions on child neurodevelopment in poor
      rural areas of China: a moderated mediation analysis.
AB  - OBJECTIVES: To examine the effects of early comprehensive interventions on home
      environment and child neurodevelopment among children younger than 3 years in
      poor rural areas of China, as well as the underlying mediating and moderating
      mechanisms. STUDY DESIGN: Non-randomized intervention study was conducted among
      216 children aged 0-3 years in Shanxi province of China. Based on a 2 * 2 factor
      design, children in Lin and Fenxi County were assigned to an intervention group
      with duration less than 1 year (n = 26) or an intervention group with duration
      longer than 1 year (n = 82), while children in Fangshan County served as a
      control group with duration less than 1 year (n = 30) or a control group with
      duration longer than 1 year (n = 78). METHODS: The control group received
      national public health services (NPHS), while the intervention group received
      NPHS plus comprehensive interventions covering health, nutrition, early
      psychosocial stimulation, and child protection. Home environment (Infant-Toddler
      Home Observation for Measurement of the Environment [HOME]) and child
      neurodevelopment (Ages and Stages Questionnaire [ASQ]) were measured by
      observation and interview with mothers after the intervention program. RESULTS:
      The intervention group showed significantly higher overall HOME, organization,
      learning materials, and involvement than the control group, only for a duration
      longer than 1 year. Children in the intervention group performed better in
      overall ASQ, fine motor, problem-solving, and personal-social than children in
      the control group. Moderated mediation analyses indicated that there were
      significantly indirect effects of treatment on overall ASQ through overall HOME,
      organization, and involvement only when the duration was longer than 1 year.
      CONCLUSIONS: Early comprehensive interventions longer than 1 year improve home
      environment and promote child neurodevelopment among children younger than 3
      years in poor rural areas. What is more, effects of early comprehensive
      interventions longer than 1 year on child neurodevelopment were mediated by home
      environment.

PMID- 29576228
TI  - Reason for immigration and immigrants' health.
AB  - OBJECTIVES: The existing literature on the health trajectories of the UK
      immigrants has mainly focussed on the relationship between ethnicity and health.
      There is little information on the role of immigration status and no previous
      information on the role of reason for immigration to the country. This study
      fills this gap in the literature by analysing the heterogeneity of immigrant
      native differences in health by reason for immigration. STUDY DESIGN: Analysis of
      cross-sectional quarterly data from the UK Labour Force Survey covering the
      period of 2010 (quarter 1) to 2017 (quarter 2). The sample includes 345,086
      observations. The dependent variables of interest include suffering from a long
      lasting condition, the link between long-lasting conditions and labour market
      performance and the prevalence of 12 specific health conditions. METHODS: Data
      were analysed using linear probability models to adjust for differences in age,
      education, gender, ethnicity, local authority of residence and year of survey.
      The analysis also explores the role of length of stay in the UK and the
      percentage of current lifetime spent in the UK (duration in the UK/age). RESULTS:
      Results indicate that, in general, immigrants are less likely than natives to
      report suffering from a long-lasting (1 year or more) health problem. This
      pattern generally remains the same when we consider the specificity of the long
      lasting health problem. However, there are key differences across the immigrant
      groups by reason for immigration. Those who migrated for employment, family and
      study reasons report better health outcomes than natives, while those who
      migrated to seek asylum report worse health outcomes than natives. There is
      convergence to natives' health outcomes over time for those who migrated for non
      asylum reasons, but not for those who migrated to seek asylum. CONCLUSIONS: The
      findings show that the prevalence of health problems differs not only between
      natives and immigrants but also across groups of immigrants who moved to the UK
      for different reasons.

PMID- 29576229
TI  - Are Post-Acute Patients with Behavioral Health Disorders Admitted to Lower
      Quality Nursing Homes?
AB  - OBJECTIVES: We measured the proportion of new post-acute nursing home admissions
      with behavioral health diagnoses and examined whether patients with these
      disorders (schizophrenia/psychosis, bipolar, depression/anxiety, personality
      disorder, and substance abuse) faced disparities in access to high quality
      facilities. SETTING/PARTICIPANTS: The analytical sample included 3,729,282
      admissions to 15,600 facilities nationwide for 2012-2014. MEASUREMENT: Quality
      was measured for overall and staffing domains reported by the Centers for
      Medicare and Medicaid Services in the Five-Star Quality Rating System.
      Multinomial logistic regression models were used. The base model included the
      diagnostic groups of interest and state dummies. Patient sociodemographics,
      functional and cognitive status, and comorbid conditions were sequentially added
      to the base model to determine the independent effect of having a behavioral
      health diagnosis at admission. RESULTS: Patients with these conditions
      experienced disparities accessing to high-quality homes compared to patients
      without. For example, patients with depression/anxiety had lower access to five
      star homes, for the staffing quality domain (Model 3 ORs = 0.88, 0.93, 0.92 in
      years 1 through 3, respectively) compared to patients with no behavioral health
      diagnosis. Access disparities were faced not only by patients with serious mental
      illness, as previously demonstrated, but also patients with substance abuse and
      with depression/anxiety who account for one-third of all new admissions.
      CONCLUSIONS: Our findings demonstrate persistence of disparities in access to
      high quality facilities over time and for patients with a broad range of
      behavioral health conditions. Further research is needed to understand the impact
      of these disparities on outcomes of patients with behavioral disorders.

PMID- 29576230
TI  - Is the 8th edition of the Union for International Cancer Control staging of oral
      cancer good enough?
AB  - Depth of invasion is an important predictor of survival. A study by the
      International Consortium (ICOR) for Outcome Research proposed incorporation of it
      (together with the greatest surface dimension, or the anatomical criteria, or
      both) into the T stage. This has been adopted in part by the 8th edition of the
      Union for International Cancer Control (UICC) TNM 8 classification of malignant
      tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of
      invasion as an independent prognostic factor, and to validate the staging by
      comparing it with that specified in the 7th edition (TNM 7) and the T-staging
      model proposed by the International Consortium. We retrospectively studied 449
      patients who had had operations for a previously untreated primary oral cancer
      between 2006 and 2014 at a single centre, and analysed the independent predictive
      value of depth of invasion for both disease-specific and overall survival. It was
      an independent predictor of disease-specific survival as were sex, perineural
      invasion, and N stage. It was also an independent predictor of overall survival
      together with sex and N status. Staging in TNM 8 gave a better balance of
      distribution than that in TNM 7, but did not discriminate between prognosis in
      patients with T3 and T4 disease. The proposed International Consortium rules for
      T-staging gave an improved balance in distribution and hazard discrimination. The
      incorporation of depth of invasion into the T-staging rules for oral SCC improved
      prognostic accuracy and is likely to influence the selection of patients for
      adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard
      discrimination in patients with locally-advanced disease because its T4 staging
      is restricted to anatomical criteria.

PMID- 29576231
TI  - Incidence of Heart Failure Observed in Emergency Departments, Ambulatory Clinics,
      and Hospitals.
AB  - Reports on the burden of heart failure (HF) have largely omitted HF diagnosed in
      outpatient settings. We quantified annual incidence rates ([IR] per 1,000 person
      years) of HF identified in ambulatory clinics, emergency departments (EDs), and
      during hospital stays in a national probability sample of Medicare beneficiaries
      from 2008 to 2014, by age and race/ethnicity. A 20% random sample of Medicare
      beneficiaries ages >=65 years with continuous Medicare Parts A, B, and D coverage
      was used to estimate annual IRs of HF identified using International
      Classification of Diseases, Ninth Revision, Clinical Modification codes. Of the
      681,487 beneficiaries with incident HF from 2008 to 2014, 283,451 (41%) presented
      in ambulatory clinics, 76,919 (11%) in EDs, and 321,117 (47%) in hospitals.
      Overall, incidence of HF in ambulatory clinics decreased from 2008 (IR 22.2, 95%
      confidence interval [CI] 22.0, 22.4) to 2014 (IR 15.0, 95% CI 14.8, 15.1).
      Similarly, incidence of HF-related ED visits without an admission to the hospital
      decreased somewhat from 2008 (IR 5.5, 95% CI 5.4, 5.6) to 2012 (IR 4.2, 95% CI
      4.1, 4.3) and stabilized from 2013 to 2014. Similar to previous reports, HF
      hospitalizations, both International Classification of Diseases, Ninth Revision,
      Clinical Modification code 428.x in the primary and any position, decreased over
      the study period. More than half of all new cases of HF in Medicare beneficiaries
      presented in an ambulatory clinic or ED. The overall incidence of HF decreased
      from 2008 to 2014, regardless of health-care setting. In conclusion,
      consideration of outpatient HF is warranted to better understand the burden of HF
      and its temporal trends.

PMID- 29576232
TI  - Controversies and Challenges of Ventricular Assist Device Therapy.
AB  - Left ventricular assist device (LVAD) therapy has emerged as an increasingly
      vital facet of the treatment algorithm for advanced heart failure. Growing
      experience with LVAD support has led to substantial improvements in outcomes,
      with 1-year survival rates approaching that of cardiac transplantation. These
      therapeutic refinements have engendered growing interests in the potential for
      expanding the clinical indications for LVAD therapy to patients with less
      advanced heart failure. The primary obstacles to this evolution of care center
      largely on the prevention and/or management of the adverse events associated with
      LVAD therapy along with patient preference. Many programs also face the mounting
      difficulty of balancing quality outcomes with the increased volume of implants.
      During the recently assembled Users Meeting organized by St. Jude Medical, heart
      failure clinicians from nearly 50 LVAD implanting centers discussed these and
      other challenges and controversies impacting the field. The present review
      summarizes the key insights gleaned from this meeting.

PMID- 29576233
TI  - Cardiac Ventricular Contractile Responses to Chronically Increased Afterload
      Secondary to Right Ventricular Outflow Obstruction in Patients With Tetralogy of
      Fallot.
AB  - We examined the adaptive mechanism of the pulmonary ventricle (PV) in response to
      increased afterload secondary to pulmonary stenosis in tetralogy of Fallot (TOF,
      n = 47) and congenitally corrected transposition of the great arteries (cCTGA, n
      = 18), where the PV is morphologically different. We also elucidated the effects
      of such adaptation on systemic ventricular (SV) function. PV contractility,
      assessed by dp/dtmax, showed significant positive correlations with PV pressure
      (r = 0.82, p <0.01 for TOF and r = 0.78, p <0.01 for cCTGA) and pulmonary-to
      systemic ventricular pressure ratio (r = 0.70, p <0.01 for TOF and r = 0.76, p
      <0.01 for cCTGA) in patients with both TOF and cCTGA. Notably, the slopes of
      these correlations were significantly higher in cCTGA than in TOF (p <0.01),
      suggesting enhanced contractile responses in cCTGA. Moreover, SV dp/dtmax showed
      significant positive correlations with PV dp/dtmax in patients with both TOF and
      cCTGA (r = 0.67, p <0.01 and r = 0.61, p <0.01, respectively), indicating
      positive ventricular-ventricular interaction. In this relationship, the slopes of
      correlations were significantly higher in TOF than in cCTGA (p = 0.024). These
      results, indicating different behaviors of PV contractile physiology and its
      interaction with the SV, may have important therapeutic implications when
      considering medical, catheter, and surgical interventions for pulmonary stenosis
      in these diseases. The results may also offer the potential for a new approach
      for improvement of prognosis, especially in cCTGA.

PMID- 29576234
TI  - Usefulness of Statins for Prevention of Venous Thromboembolism.
AB  - Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary
      embolism, is common with an annual incidence of 1 to 5 per 1,000, resulting in
      major morbidity, mortality, and increased health care costs. It is more common in
      the elderly, obese, those with cancer, those undergoing surgery, and those with
      previous VTE. Strategy to reduce its occurrence has important public health
      implications. Pleotropic effects of statins may have beneficial effects on a
      number of potential targets associated with VTE. Statins have excellent safety
      profile and seem to be associated with beneficial effects in VTE in case-control
      studies, large observational studies, meta-analyses, and a randomized trial. In
      conclusion, after critically reviewing the clinical data supporting statin use in
      the prevention of VTE, we presented clinical recommendations for the use of
      statins in reducing VTE occurrence, especially in high-risk situations.

PMID- 29576235
TI  - Meta-Analysis Comparing Neurohumoral Antagonist Use in Patients >=75 Years Versus
      <75 Years Receiving Cardiac Resynchronization Therapy.
AB  - Neurohumoral antagonists are the foundation of heart failure therapy in patients
      with reduced left ventricular ejection fraction. Cardiac resynchronization
      therapy (CRT) has also been associated with improved outcomes in these patients.
      We aimed to evaluate the use of neurohumoral antagonists in patients >=75 years
      compared with <75 years of age receiving CRT. We searched electronic databases,
      up to December 20, 2016 for all studies reporting medication use in patients >=75
      years and <75 years of age who received CRT. We used random-effects meta-analysis
      models to summarize the studies. We retained 12 studies (1 randomized trial and
      11 observational studies) enrolling 5,728 >=75 years old and 9,549 patients of
      <75 years old. There were lower use of angiotensin converting enzyme inhibitors
      or angiotensin receptor blockers in patients >=75 years compared with patients
      <75 years (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.47 to 0.74, p <
      0.0001). In addition, there were lower use of mineralocorticoid receptor
      antagonists in patients >=75 years compared with patients <75 years (OR 0.48, 95%
      CI 0.40 to 0.57, p < 0.0001). The use of beta blockers was nonsignificantly lower
      in patients >=75 years compared with patients <75 years (OR 0.70, 95% CI 0.47 to
      1.03, p = 0.07). In conclusion, neurohumoral antagonists appeared to be underused
      in patients >=75 years compared with patients <75 years receiving CRT.
      Consideration should be given to increase neurohumoral antagonism in patients
      >=75 years referred for CRT.

PMID- 29576237
TI  - Errata.

PMID- 29576236
TI  - Relation of Resting Heart Rate to Incident Atrial Fibrillation (From ARIC
      [Atherosclerosis Risk in Communities] Study).
AB  - The evidence on the association between resting heart rate (HR) and incident
      atrial fibrillation (AF) is conflicting. Whether change in resting HR is
      associated with incident AF is unknown. We evaluated 11,545 participants (mean
      [+/-standard deviation] age: 57 +/- 5.7 years) free of AF at baseline (1990 to
      1992). Resting HR was obtained from 10-second electrocardiograms at baseline and
      3 years later. AF diagnosis was ascertained from visit electrocardiograms,
      hospital discharge records, and death certificates through 2013. High and low
      resting HR were defined as >=80 and <55 beats/min, respectively. Increase and
      decrease in HR were defined as a 3-year HR difference >15 and <-15 beats/min,
      respectively. Over a median follow-up of 22.5 years, 1,746 (15%) participants
      developed AF. Both baseline high resting HR and increase in HR were independently
      associated with incident AF (hazard ratio = 1.2, 95% confidence interval = 1.0 to
      1.5 and hazard ratio = 1.4, 95% confidence interval = 1.1 to 1.9). Increase in HR
      was no longer associated with incident AF after additional adjustment for
      incident heart failure. In stratified analyses, increase in HR was associated
      only with AF in participants <60 years, with bachelor's degree or above, without
      diabetes, and without hypertension (p values for interaction <=0.05). In
      conclusion, in a middle-aged population, high resting HR is associated with
      higher AF risk. Increase in resting HR is also associated with higher AF risk,
      especially in individuals without traditional AF risk factors. Whether
      interventions to decrease HR can prevent AF remain to be examined.

PMID- 29576238
TI  - Erratum.

PMID- 29576239
TI  - Epidemiology and outcomes of traumatic knee dislocations: Isolated vs multi
      trauma injuries.
AB  - BACKGROUND AND PURPOSE: Traumatic dislocation of the knee (TKD) is a rare injury,
      accounting for approximately 0.02% of orthopaedic injuries. They are a
      challenging entity for orthopaedic surgeons to manage, and can have devastating
      consequences. The aim of this study was to describe the epidemiology of traumatic
      knee dislocations (TKD'S) and contrast the incidence of neurovascular injury
      between isolated and multi-trauma dislocations as well as key patient reported
      outcomes achieved between these groups. MATERIAL AND METHODS: Patients who had a
      traumatic disruption of the tibiofemoral articulation between March 1 2007 and
      February 31, 2015 were identified from the Victorian Orthopaedic Trauma Outcomes
      Registry (VOTOR). Data was cross-checked with medical records and radiological
      reports to confirm true multi-ligamentous dislocation. VOTOR collects information
      pertaining to orthopaedic injuries, treatment, complications and outcomes from
      four adult hospitals in Victoria, Australia, including the major trauma centers.
      Patient-reported outcomes are collected by VOTOR at 12 months post-injury
      including the EQ-5D-3L (EQ-5D) and Glasgow Extended Outcome Scores (GOS-E) and
      return to work status. Patient reported functional and quality of life outcomes
      at 12 months after injury were analysed. RESULTS: A cohort of 88 patients were
      identified that fit the inclusion criteria for the study, and at 12 months post
      injury there was data available for 80 patients (90.9%). There were 38 (42.9%)
      patients who experienced an isolated traumatic knee dislocation and 52 (57.1%)
      who experienced a traumatic knee dislocation in association with another injury.
      Of the 88 patients identified as eligible for the study, two had bilateral knee
      dislocations, hence there were 90 multi-ligamentous knee injuries. Those who were
      injured at a higher velocity were more likely to have additional injuries.
      Dislocations that occurred at a lower velocity were shown to have better overall
      outcomes, as did dislocations that occurred in isolation. CONCLUSIONS: Traumatic
      knee dislocations that occur in isolation typically result in better outcomes
      than those that occur with associated injuries. TKD's are a rare but severe
      injury that requires further research in order for functional outcomes to be
      optimized.

PMID- 29576240
TI  - Question 1: Why do children still die from asthma?
AB  - Asthma is one of the commonest chronic conditions in children and can
      occasionally be fatal. Little has changed regarding the risk factors for children
      dying from asthma in the last 30 years. The majority of deaths from asthma occur
      in children from socio-economically disadvantaged backgrounds. These should be
      preventable with better education of families, oversight of medication adherence
      and improved communication between health care professionals and families. More
      needs to be done to deliver basic messages more effectively about asthma
      management to the most vulnerable in communities around the world.

PMID- 29576241
TI  - Synthesis, characterization and DNA interactions of [Pt3(TPymT)Cl3], the
      trinuclear platinum(II) complex of the TPymT ligand.
AB  - The triplatinum complex of the 2,4,6-Tris(2-pyrimidyl)-1,3,5-triazine ligand,
      Pt3TPymT hereafter, has been prepared and characterized for the first time. NMR
      studies point out that the three platinum(II) centers possess an identical
      coordination environment. The interactions of Pt3TPymT with DNA were explored in
      comparison to the free ligand. Specifically, fluorescence, mass spectrometry,
      viscometry and melting measurements were carried out. In contrast to
      expectations, the obtained data reveal that no intercalative binding takes place;
      we propose that binding of Pt3TPymT to DNA mainly occurs through external/groove
      binding.

PMID- 29576243
TI  - Corrigendum to "People learn other people's preferences through inverse decision
      making" [Cognition 168 (2017) 46-64].

PMID- 29576242
TI  - Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine
      desulfurase complex leading to Fe-S cluster assembly.
AB  - Frataxin (FXN) is involved in mitochondrial iron-sulfur (Fe-S) cluster biogenesis
      and serves to accelerate Fe-S cluster formation. FXN deficiency is associated
      with Friedreich ataxia, a neurodegenerative disease. We have used a combination
      of isothermal titration calorimetry and multinuclear NMR spectroscopy to
      investigate interactions among the components of the biological machine that
      carries out the assembly of iron-sulfur clusters in human mitochondria. Our
      results show that FXN tightly binds a single Fe2+ but not Fe3+. While FXN (with
      or without bound Fe2+) does not bind the scaffold protein ISCU directly, the two
      proteins interact mutually when each is bound to the cysteine desulfurase complex
      ([NFS1]2:[ISD11]2:[Acp]2), abbreviated as (NIA)2, where "N" represents the
      cysteine desulfurase (NFS1), "I" represents the accessory protein (ISD11), and
      "A" represents acyl carrier protein (Acp). FXN binds (NIA)2 weakly in the absence
      of ISCU but more strongly in its presence. Fe2+-FXN binds to the (NIA)2-ISCU2
      complex without release of iron. However, upon the addition of both l-cysteine
      and a reductant (either reduced FDX2 or DTT), Fe2+ is released from FXN as
      consistent with Fe2+-FXN being the proximal source of iron for Fe-S cluster
      assembly.

PMID- 29576244
TI  - Exploring the training and scope of practice of GPs in England, Germany and
      Spain.
AB  - OBJECTIVE: To explore general practitioner (GP) training, continuing professional
      development, scope of practice, ethical issues and challenges in the working
      environment in three European countries. METHOD: Qualitative study of 35 GPs from
      England, Germany and Spain working in urban primary care practices. Participants
      were recruited using convenience and snowball sampling techniques. Semi
      structured interviews were recorded, transcribed and analysed by four independent
      researchers adopting a thematic approach. RESULTS: Entrance to and length of GP
      training differ between the three countries, while continuing professional
      development is required in all three, although with different characteristics.
      Key variations in the scope of practice include whether there is a gatekeeping
      role, whether GPs work in multidisciplinary teams or singlehandedly, the
      existence of appraisal processes, and the balance between administrative and
      clinical tasks. However, similar challenges, including the need to adapt to an
      ageing population, end-of-life care, ethical dilemmas, the impact of austerity
      measures, limited time for patients and gaps in coordination between primary and
      secondary care are experienced by GPs in all three countries. CONCLUSION: Primary
      health care variations have strong historical roots, derived from the different
      national experiences and the range of clinical services delivered by GPs. There
      is a need for an accessible source of information for GPs themselves and those
      responsible for safety and quality standards of the healthcare workforce. This
      paper maps out the current situation before Brexit is being implemented in the UK
      which could see many of the current EU arrangements and legislation to assure
      professional mobility between the UK and the rest of Europe dismantled.

PMID- 29576245
TI  - The science of caregiving bringing voices together: Summary of National Institute
      of Nursing Research's 2017 summit.

PMID- 29576246
TI  - Autoantibodies targeting TLR and SMAD pathways define new subgroups in systemic
      lupus erythematosus.
AB  - OBJECTIVES: The molecular targets of the vast majority of autoantibodies in
      systemic lupus erythematosus (SLE) are unknown. We set out to identify novel
      autoantibodies in SLE to improve diagnosis and identify subgroups of SLE
      individuals. METHODS: A baculovirus-insect cell expression system was used to
      create an advanced protein microarray with 1543 full-length human proteins
      expressed with a biotin carboxyl carrier protein (BCCP) folding tag, to enrich
      for correctly folded proteins. Sera from a discovery cohort of UK and US SLE
      individuals (n = 186) and age/ethnicity matched controls (n = 188) were assayed
      using the microarray to identify novel autoantibodies. Autoantibodies were
      validated in a second validation cohort (91 SLE, 92 controls) and a confounding
      rheumatic disease cohort (n = 92). RESULTS: We confirmed 68 novel proteins as
      autoantigens in SLE and 11 previous autoantigens in both cohorts (FDR<0.05).
      Using hierarchical clustering and principal component analysis, we observed four
      subgroups of SLE individuals associated with four corresponding clusters of
      functionally linked autoantigens. Two clusters of novel autoantigens revealed
      distinctive networks of interacting proteins: SMAD2, SMAD5 and proteins linked to
      TGF-beta signalling; and MyD88 and proteins involved in TLR signalling,
      apoptosis, NF-kappaB regulation and lymphocyte development. The autoantibody
      clusters were associated with different patterns of organ involvement (arthritis,
      pulmonary, renal and neurological). A panel of 26 autoantibodies, which accounted
      for four SLE clusters, showed improved diagnostic accuracy compared to
      conventional antinuclear antibody and anti-dsDNA antibody assays. CONCLUSIONS:
      These data suggest that the novel SLE autoantibody clusters may be of prognostic
      utility for predicting organ involvement in SLE patients and for stratifying SLE
      patients for specific therapies.

PMID- 29576248
TI  - Ultrasound-Guided Percutaneous Core Needle Biopsy for the Diagnosis of Pancreatic
      Disease.
AB  - Few studies have evaluated the performance of percutaneous core needle biopsies
      of the pancreas. This article is an overview of the advantages, disadvantages,
      predictive power and complications associated with percutaneous ultrasound-guided
      core needle biopsies of pancreatic lesions. A comprehensive literature search of
      Medline (using PubMed as the search engine) and EMBASE was done to identify
      suitable studies up to March 2017. A study of quantitative pre-operative
      pancreatic biopsy data was reported. Lesion location, mean or median number of
      passes, inadequate tissue or technical failures and complications were assessed
      for all cases by reviewing clinical notes and post-procedural imaging. The
      analysis included 13 studies, mostly of a retrospective nature. The sensitivity
      (mean: 94.42%, range: 90%-100%) and specificity (mean: 97.94%, range: 94.7%-100%)
      of the procedure were high, and the mean accuracy of diagnosis was 95.76 (range:
      91-100). Furthermore, the procedure had a high negative predictive value of
      approximately 76.26%. Of the 13 reported studies, 7.3% were inadequate or
      technical failure cases. The mean rate of complications was 2.08%, which seemed
      similar to the lower limit of this rate for endoscopic ultrasound-guided fine
      needle aspirations. The risk of tumor seeding with ultrasound-guided core needle
      biopsies was not reported in the included articles. With the development of
      technology, ultrasound-guided percutaneous core needle biopsy for pancreatic
      lesions is increasingly available and has optimal diagnostic power in pancreatic
      neoplasms.

PMID- 29576247
TI  - "Tweet"-Format Writing Is an Effective Tool for Medical Student Reflection.
AB  - OBJECTIVE: Reflective writing during medical education allows for professional
      growth through retrospective analysis of experiential knowledge. However, these
      writing assignments can pose a challenge to millennial medical students who are
      more likely to assimilate knowledge through the use of innovative technology and
      who prefer their data in a concise format. Here, we present a novel, tweet-style
      reflective writing assignment to better engage the unique skill set of today's
      medical students. We analyzed the written content partway through the year to
      determine whether or not the format retains the impact of longer, more structured
      reflective writing assignments. DESIGN: Surgical clerkship students were required
      to reflect on 3 distinct experiences through a 140-character written reflection,
      or tweet. Students were able to submit these assignments at any point during
      their rotation through a platform available on their smartphone or computer.
      There were no specifications with regard to content. These reflections were
      analyzed using modified grounded theory methods. Each tweet was analyzed by 2
      individuals to ensure intercoder reliability. Codes were created a priori with
      respect to positive and negative domains, and type of experience. STETTING:
      Department of Surgery, Warren Alpert School of Medicine, Brown University, Third
      Year Medical Student Surgical Clerkship. PARTICIPANTS: Third year medical
      students at the Warren Alpert School of Medicine, Brown University. Fifty-six
      medical students were included in this study. RESULTS: During the first 4 blocks
      of the 2016-2017 academic year, 56 students rotated through the third year
      surgical clerkship. One hundred and sixty-eight tweets were collected and coded.
      Sixty-nine tweets (42%) had a positive valence. Students reflected on the
      following experiences: patient interaction (54%), surgical education (34%),
      physician/resident interaction (27%), and career decisions (11%). Overall, 87
      (52%) tweets were reflective. Many tweets included emotional reactions to
      specific experiences. CONCLUSIONS: Using tweet-style reflective writing, students
      identified and reacted to multiple salient experiences from their surgical
      clerkship. They reflected on both positive and negative emotions, mostly related
      to personal interactions with patients, but also associated with their education,
      their team, and their future career. Based on early analysis of the data, we
      believe that short format writing can be an effective format for reflection.

PMID- 29576249
TI  - A case report of breathlessness on exertion with an asymptomatic honeymoon
      period.

PMID- 29576250
TI  - Dietary inflammatory index or Mediterranean diet score as risk factors for total
      and cardiovascular mortality.
AB  - BACKGROUND AND AIMS: Dietary patterns are associated with risk of cardiovascular
      disease (CVD). We aimed to examine associations of the Dietary Inflammatory Index
      (DII) and the Mediterranean Diet Score (MDS) with total, cardiovascular disease
      (CVD) and coronary heart disease (CHD) mortality in the Melbourne Collaborative
      Cohort Study; and compare the strengths of the associations. METHODS AND RESULTS:
      In our prospective cohort study of 41,513 men and women aged 40-69 years, a food
      frequency questionnaire was completed at baseline and mortality data were
      obtained via linkage with local and national registries over an average of 19
      years follow up. At baseline, questionnaires were completed and physical measures
      and blood samples taken. Cox proportional hazards models, adjusting for age,
      alcohol consumption, sex, region of origin, personal history of CVD or diabetes
      and family history of CVD, were used to assess associations between dietary
      scores and mortality. More Mediterranean or less inflammatory diets were
      associated with lower total, CVD and CHD mortality. The hazard ratio for total
      mortality comparing the highest and lowest quintiles was 1.16 (95%CI: 1.08-1.24)
      for DII; and 0.86 (95%CI: 0.80-0.93) comparing the highest and lowest three
      categories of MDS. Using the Bayesian information criterion, there was no
      evidence that the DII score was more strongly associated with total and CVD
      mortality than was the MDS. CONCLUSIONS: The MDI and the DII show similar
      associations with total and cardiovascular mortality, consistent with the
      consensus that plant-based diets are beneficial for health.

PMID- 29576251
TI  - [Octogenarian with rheumatoid arthritis, low-grade fever, severe pericardial
      effusion, and splenomegaly].

PMID- 29576252
TI  - A Scoping Review of Photovoice Research Among People With HIV.
AB  - We describe how Photovoice-a participatory method in which people express and
      share ideas via images-has been used in research with people living with HIV
      (PLWH). Four databases, reference lists, and journal tables of content were
      searched to identify peer-reviewed original research, in English, using
      Photovoice with a sample of PLWH, between 1994 and 2016. Of 1,898 citations
      identified, 22 studies were included. Studies included a mean of 18 (range 4-38)
      participants. Studies were of strong quality but lacked consistent procedures.
      Goals varied and projects included different combinations of introductory, photo
      training, ethics, group, individual, and exhibit sessions. Descriptions of the
      researcher-participant relationship were uneven. Photovoice allowed PLWH to
      inform research and practice priorities through their own visual perspectives.
      Continued use of Photovoice with PLWH is recommended with greater emphasis on
      consistent methods and detailed reporting; more studies should be undertaken
      resulting in actions or advocacy.

PMID- 29576253
TI  - Nutritional management of cow's milk allergy in children: An update.
AB  - Cow's milk is one of the most common foods responsible for allergic reactions in
      children. Cow's milk allergy (CMA) involves immunoglobulin E (IgE)- and non-IgE
      mediated reactions, the latter being both variable and nonspecific. Guidelines
      thus emphasize the need for physicians to recognize the specific syndromes of CMA
      and to respect strict diagnostic modalities. Whatever the clinical pattern of
      CMA, the mainstay of treatment is the elimination from the diet of cow's milk
      proteins. The challenge is that both the disease and the elimination diet may
      result in insufficient height and weight gain and bone mineralization. If, during
      CMA, the mother is not able or willing to breastfeed, the child must be fed a
      formula adapted to CMA dietary management, during infancy and later, if the
      disease persists. This type of formula must be adequate in terms of allergic
      efficacy and nutritional safety. In older children, when CMA persists, the use of
      cow's milk baked or heated at a sufficient temperature, frequently tolerated by
      children with CMA, may help alleviate the stringency of the elimination diet.
      Guidance on the implementation of the elimination diet by qualified healthcare
      professionals is always necessary. This guidance should also include advice to
      ensure adequate bone growth, especially relating to calcium intake. Specific
      attention should be given to children presenting with several risk factors for
      weak bone mineral density, i.e., multiple food allergies, vitamin D deficiency,
      poor sun exposure, steroid use, or severe eczema. When CMA is outgrown, a
      prolonged elimination diet may negatively impact the quality of the diet over the
      long term.

PMID- 29576255
TI  - First description of the alpha lipoic acid intoxication in an adult patient
      worldwide following oral administration.

PMID- 29576254
TI  - CD36 gene polymorphism and plasma sCD36 as the risk factor in higher
      cholesterolemia.
AB  - INTRODUCTION: The receptor CD36 has been reported to play an important role in
      atherogenicity. The aim of this study was to gain insight into the relationship
      between CD36 gene polymorphisms or the plasma concentration of sCD36 and clinical
      or biochemical parameters in children. PATIENTS AND METHODS: The study groups
      comprised Caucasian children with and without hypercholesterolemia. The
      alterations in the CD36 gene were detected by DHPLC and the plasma concentrations
      of sCD36 were measured by ELISA. RESULTS: The data presented suggest that the
      IVS4-10A allele of CD36 (rs3211892) is associated with a lower risk of
      hypercholesterolemia. We observed a negative correlation of the sCD36
      concentration with uric acid and insulin concentrations, the HOMA-IR ratio,
      weight, waist and hip circumference, systolic blood pressure, body mass index,
      waist-hip ratio and mean arterial pressure ratio, but a positive correlation with
      HDL cholesterol and ApoA1 concentrations. Female gender was a significant
      independent predictor of a higher plasma sCD36 concentration. CONCLUSIONS: The
      data presented suggest a possible protective effect of a higher sCD36
      concentration in relation to metabolic syndrome components.

PMID- 29576256
TI  - Clarity needed as to the optimal dose and volume of local anesthetic for erector
      spinae plane blockade for posterior rib fractures.

PMID- 29576257
TI  - Mortality outcomes based on ED qSOFA score and HIV status in a developing low
      income country.
AB  - OBJECTIVE: To evaluate the utility of the quick Sepsis-related Organ Failure
      Assessment (qSOFA) score to predict risks for emergency department (ED) and
      hospital mortality among patients in a sub-Saharan Africa (SSA) setting. METHODS:
      This retrospective cohort study was carried out at a tertiary-care hospital, in
      Kigali, Rwanda and included patients >=15years, presenting for ED care during
      2013 with an infectious disease (ID). ED and overall hospital mortality were
      evaluated using multivariable regression, with qSOFA scores as the primary
      predictor (reference: qSOFA=0), to yield adjusted relative risks (aRR) with 95%
      confidence intervals (CI). Analyses were performed for the overall population and
      stratified by HIV status. RESULTS: Among 15,748 cases, 760 met inclusion (HIV
      infected 197). The most common diagnoses were malaria and intra-abdominal
      infections. Prevalence of ED and hospital mortality were 12.5% and 25.4%
      respectively. In the overall population, ED mortality aRR was 4.8 (95% CI 1.9
      12.0) for qSOFA scores equal to 1 and 7.8 (95% CI 3.1-19.7) for qSOFA scores >=2.
      The aRR for hospital mortality in the overall cohort was 2.6 (95% 1.6-4.1) for
      qSOFA scores equal to 1 and 3.8 (95% 2.4-6.0) for qSOFA scores >=2. For HIV
      infected cases, although proportional mortality increased with greater qSOFA
      score, statistically significant risk differences were not identified.
      CONCLUSION: The qSOFA score provided risk stratification for both ED and hospital
      mortality outcomes in the setting studied, indicating utility in sepsis care in
      SSA, however, further prospective study in high-burden HIV populations is needed.

PMID- 29576258
TI  - Are acute care settings amenable to addressing patient social needs: A sub-group
      analysis.

PMID- 29576259
TI  - The stiff heart: Can we more safely navigate heart surgery?

PMID- 29576260
TI  - A novel tourniquet technique for transient pulmonary artery occlusion during
      video-assisted thoracoscopic surgery.

PMID- 29576262
TI  - Gambling with esophageal cancer: May the odds be in your favor!

PMID- 29576261
TI  - Outcomes and prognostic factors for postsurgical pulmonary vein stenosis in the
      current era.
AB  - BACKGROUND: The optimal management and prognostic factors of postsurgical
      pulmonary vein stenosis remain controversial. We sought to determine current
      postsurgical pulmonary vein stenosis outcomes and prognostic factors in a
      multicentric study in the current era. METHODS: Seventy-five patients with
      postsurgical pulmonary vein stenosis who underwent 103 procedures in 14
      European/North American centers (2000-2012) were included retrospectively. A
      specific pulmonary vein stenosis severity score was developed on the basis of the
      assessment of each pulmonary vein. End points were death, pulmonary vein
      reintervention, and restenosis. A univariate and multivariate risk analysis was
      performed. RESULTS: Some 76% of postsurgical pulmonary vein stenosis occurred
      after repair of a total anomalous pulmonary venous return. Sutureless repair was
      used in 42 of 103 procedures (41%), patch veinoplasty was used in 28 procedures
      (27%), and endarterectomy was used in 16 procedures (16%). Overall pulmonary vein
      restenosis, reintervention, and mortality occurred in 56% (n = 58/103), 49% (n =
      50/103), and 27% (n = 20/75), respectively. Sutureless repair was associated with
      less restenosis (40% vs 67%; P = .007) and less reintervention (31% vs 61%; P =
      .003). Mortality after sutureless repair (20%; 7/35) tends to be lower than after
      nonsutureless repair (33%; 13/40) (P = .22). A high postoperative residual
      pulmonary vein stenosis score at the time of hospital discharge was an
      independent risk factor for restenosis (hazard ratio [HR], 1.55; P < 10-4),
      reintervention (HR, 1.33; P < 10-4), and mortality (HR, 1.37; P < 10-4). The
      sutureless technique was an independent protective factor against restenosis (HR,
      0.27; P = .006). CONCLUSIONS: Postsurgical pulmonary vein stenosis still has a
      guarded prognosis in the current era. The sutureless technique is an independent
      protective factor against restenosis. The severity of the residual disease
      evaluated by a new severity score is an independent risk factor for poor outcomes
      regardless of surgical technique.

PMID- 29576263
TI  - Sequencing a super multiple synchronous lung cancer reveals a novel variant in
      driver gene ARID1B.

PMID- 29576264
TI  - Heart transplant after profoundly extended ambulatory central venoarterial
      extracorporeal membrane oxygenation.

PMID- 29576265
TI  - Cost-effectiveness of Pembrolizumab in Second-line Advanced Bladder Cancer.
AB  - BACKGROUND: Immune-modulating drugs have recently been introduced to the second
      line setting of advanced bladder cancer. Pembrolizumab increases overall survival
      and is associated with less toxicity compared with chemotherapy in this setting
      based on the Keynote 045 study. The high cost of immunotherapy necessitates an
      assessment of its value by considering both efficacy and cost. OBJECTIVE: To
      estimate the cost-effectiveness of pembrolizumab for the second-line treatment of
      advanced bladder cancer from the perspective of payers in multiple countries.
      DESIGN, SETTING, AND PARTICIPANTS: We developed a Markov model to compare the
      cost and effectiveness of pembrolizumab with those of chemotherapy in the second
      line treatment of advanced bladder cancer based on the Keynote 045 study. Drug
      costs were acquired for the United States (US), United Kingdom (UK), Canada, and
      Australia. All costs were converted from local currency to US dollars at the
      exchange rates in September 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Health outcomes were measured in quality-adjusted life-years (QALYs). RESULTS AND
      LIMITATIONS: Pembrolizumab generated a gain of 0.36-0.37 QALYs compared with
      chemotherapy. Our analysis established the following incremental cost
      effectiveness ratios (ICERs) for pembrolizumab versus chemotherapy in second-line
      advanced bladder cancer treatment: US $122 557/QALY; UK $91 995/QALY; Canada $90
      099/QALY; and Australia $99 966/QALY. The willingness-to-pay (WTP) thresholds per
      QALY are considered to be around 100 000-150 000 US dollars for the US, 20 000-50
      000 pounds for the UK (US$25 000-65 000), 20 000-100 000 CAD for Canada (US$16
      000-80 000), and 40 000-75 000 AUD for Australia (US$32 000-60 000). CONCLUSIONS:
      Cost-effectiveness and WTP thresholds vary between countries. Compared with the
      other countries examined, US drug prices were found to be the highest, leading to
      the highest ICER. With standard WTP thresholds, pembrolizumab may be considered
      cost-effective in the US but not in the other countries examined. PATIENT
      SUMMARY: This article assessed the cost-effectiveness of pembrolizumab for the
      treatment of patients with metastatic bladder cancer who had previously failed
      one treatment regimen. It would cost $122 557 in the United States, $91 995 in
      the United Kingdom, $90 099 in Canada, and $99 966 in Australia to gain one
      quality-adjusted life-year with pembrolizumab versus chemotherapy in these
      patients, which may be considered cost-effective only in the United States
      because of the differences in willingness-to-pay thresholds.

PMID- 29576266
TI  - Exploring lipid markers of the quality of coix seeds with different geographical
      origins using supercritical fluid chromatography mass spectrometry and
      chemometrics.
AB  - BACKGROUND: Lipids, a group of primary metabolites, could be used as quality
      markers of Traditional Chinese medicine. PURPOSE: The present study was designed
      to develop a research method to explore lipid markers of the quality of coix
      seeds with different geographical origins. STUDY DESIGN: The geographical origins
      of coix seeds were divided into three regions based on the latitude. A central
      composite design (CCD test) was used to optimize the chromatographic parameters
      of supercritical fluid chromatography to obtain optimal lipid profile of coix
      seed. METHODS: An untargeted method based on ultra-performance convergence
      chromatography - quadrupole/time-of-flight hybrid mass spectrometry (UPC2-QTOF)
      was developed. Four chromatographic parameters were optimized using CCD test, and
      a fusion index established by Derringer function was used to evaluate. The lipid
      profile of 27 batches of coix seeds were acquired and processed by Progenesis QI
      software, and the MS/MS spectrums were obtained to identify, simultaneously. The
      difference lipids were explored by orthogonal partial least squares discriminant
      analysis (OPLS-DA). The lipids that showed differences depending on their seeds'
      geographical origin were selected as markers of the quality of coix seeds from
      the three regions. RESULTS: A Torus 2-PIC (1.7 um, 100 mm * 3.0 mm) was selected
      as the optimal column of the untargeted method which the run time was only 8
      minutes. From the CCD test, the interaction of chromatographic parameters between
      column temperature and backpressure was founded which the optimal parameters were
      55  degrees C and 2600 psi, respectively. Thirty-two peaks in the lipid profile
      of coix seed were tentatively identified, of which 20 were triglyceride, and 12
      were diglyceride. Nine features that could potentially be used to distinguish the
      coix seeds by their geographical origin were identified, most of which were
      diglycerides, such as OP. CONCLUSIONS: Our findings confirm that UPC2-QTOF
      combined with chemometrics could be used as an efficient method for exploring
      potential lipid markers of the quality of herbal medicine.

PMID- 29576267
TI  - Interaction between the Opioid Receptor OPRM1 Gene and Mother-Child Language
      Style Matching Prospectively Predicts Children's Separation Anxiety Disorder
      Symptoms.
AB  - Recent research suggests that lower mother-child language style matching (LSM) is
      associated with greater physiological reactivity and insecure attachment in
      school-aged children, but to date no studies have explored this measure of parent
      child behavioral matching for its association with children's anxiety symptoms, a
      well-known correlate of attachment insecurity and heightened physiological
      reactivity. There is also considerable evidence of genetic risk for anxiety,
      including possession of the OPRM1 minor allele, 118G. In the current study (N =
      44), we expand upon what is known about children's genetic and environmental risk
      for anxiety by examining the unique and interactive effects of mother-child LSM
      and the OPRM1 polymorphism A118G on school-aged children's separation anxiety
      disorder (SAD) symptoms. SAD symptoms were measured both concurrently with LSM
      and OPRM1 genotype and two years later through self-report. No significant
      associations emerged between LSM or OPRM1 and concurrent Time 1 SAD symptoms.
      However, lower LSM and 118G minor allele possession were both associated with
      greater SAD symptoms at Time 2; further, the interaction between LSM and OPRM1
      genotype significantly predicted SAD symptoms beyond the main effects of the two
      variables. Possession of the minor allele was only associated with greater SAD
      symptoms among children in low LSM dyads, whereas children with the minor allele
      in high LSM dyads showed non-significantly lower SAD symptoms. These findings and
      a proportion affected analysis provide support for a differential susceptibility
      model of gene by environment interactions for the OPRM1 gene. We discuss the
      implications for predicting children's separation anxiety across development.

PMID- 29576268
TI  - Corrections.

PMID- 29576269
TI  - The risk of prostate cancer mortality and cardiovascular mortality of
      nonmetastatic prostate cancer patients: A population-based retrospective cohort
      study.
AB  - PURPOSE: To assess the risk of prostate cancer (PCa) specific mortality (PCSM)
      compared to cardiovascular disease mortality (CVDM), or other-cause mortality
      (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary
      treatment, and age. PATIENTS AND METHODS: This retrospective population-based
      cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry
      Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich.
      Multiple imputation methods were applied to handle missing PCa information. Fine
      and Gray competing risk regression analysis was used to estimate subdistribution
      hazard ratios for the outcomes PCSM, CVDM, or OCM RESULTS: Ten years after
      diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%,
      respectively. We observed an increased adjusted risk of PCSM in men treated with
      androgen deprivation therapy (ADT) compared to surgery, but could not observe an
      association between ADT and CVDM. The probability of PCSM was significantly
      higher for patients on active surveillance or watchful waiting, compared to
      surgery. Age and PCa risk categories were positively associated with risk of
      PCSM, whereas there was no evidence for an association with CVDM or OCM based on
      risk groups. CONCLUSIONS: Overall, men with PCa were more likely to die from non
      PCa related outcomes. Nevertheless, the analyses showed a high proportion of PCSM
      among men on ADT, older men and men with a high-risk tumor. However, further
      research is needed to understand comprehensively the benefits of the respective
      treatments.

PMID- 29576270
TI  - Synthesis and biological evaluation of pyrimidine derivatives as novel human Pin1
      inhibitors.
AB  - Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the
      amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of
      Pin1 might be a novel strategy for developing anticancer agents. Herein, a series
      of pyrimidine derivatives were synthesized and their Pin1 inhibitory activities
      were evaluated. Among them, four compounds (2a, 2f, 2h and 2l) displayed potent
      inhibitory activities against Pin1 with IC50 values lower than 3 uM. This series
      of pyrimidine-based inhibitors presented time-dependent inhibition against Pin1.
      The structure-activity relationships on the 2-, 4- and 5-positions of the
      pyrimidine ring were analyzed in details, which would facilitate further
      exploration of new Pin1 inhibitors.

PMID- 29576271
TI  - 2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD
      hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity
      relationships.
AB  - Starting from 4-amino-8-quinoline carboxamide lead 1a and scaffold hopping to the
      chemically more tractable quinazoline, a systematic exploration of the 2
      substituents of the quinazoline ring, utilizing structure activity relationships
      and conformational constraint, resulted in the identification of 39 novel CD38
      inhibitors. Eight of these analogs were 10-100-fold more potent human CD38
      inhibitors, including the single digit nanomolar inhibitor 1am. Several of these
      molecules also exhibited improved therapeutic indices relative to hERG activity.
      A representative analog 1r exhibited suitable pharmacokinetic parameters for in
      vivo animal studies, including moderate clearance and good oral bioavailability.
      These inhibitor compounds will aid in the exploration of the enzymatic functions
      of CD38, as well as furthering the study of the therapeutic implications of NAD
      enhancement in metabolic disease models.

PMID- 29576272
TI  - Synthesis and evaluation of 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H
      purine as new EGFR inhibitors.
AB  - In present study, we described the synthesis and biological evaluation of a new
      class of EGFR inhibitors containing 2,9-disubstituted 8-phenylthio/phenylsulfinyl
      9H-purine scaffold. Thirty-one compounds were synthesized. Among them, compound
      C9 displayed the IC50 of 29.4 nM against HCC827 cell line and 1.9 nM against
      EGFRL858R. Compound C12 showed moderate inhibitory activity against
      EGFRL858R/T790M/C797S (IC50 = 114 nM). Western bolt assay suggested that compound
      C9 significantly inhibited EGFR phosphorylation. In vivo test, compound C9
      remarkably exhibited inhibitory effect on tumor growth at 5.0 mg/kg by oral
      administration in established nude mouse HCC827 xenograft model. These results
      indicate that the 2,9-disubstituted 8-phenylsulfinyl/phenylsulfinyl-9H-purine
      derivatives can act as potent EGFR(L858R) inhibitors and effective anticancer
      agents. Additionally, optimization of compound C12 may result in discovering the
      fourth-generation EGFR-TKIs.

PMID- 29576273
TI  - Knowledge translation and the health of people with disability.

PMID- 29576274
TI  - Corrigendum to "Associations between neurodevelopmental disorders and factors
      related to school, health, and social interaction in schoolchildren: Results from
      a Swedish population-based survey" [Disabil Health J 9(4) (2016) 663-672].

PMID- 29576275
TI  - Liquid chromatography - high resolution mass spectrometry method for monitoring
      of 17 mycotoxins in human plasma for exposure studies.
AB  - Mycotoxins are secondary metabolites produced by filamentous fungi. Primary route
      of human exposure to mycotoxins is the intake of the contaminated food.
      Minimizing mycotoxin exposure is important for population health, as their
      chronic toxic effects have been associated with kidney and liver diseases, some
      types of cancer and immunosuppression. The objective of this work was to develop
      and validate a multi-class mycotoxin method suitable for exposure monitoring of
      mycotoxins in human plasma. A sensitive liquid chromatography - mass spectrometry
      method was developed for 17 mycotoxins: nivalenol (NIV), deoxynivalenol,
      fusarenon X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, T-2 toxin, HT-2
      toxin, aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, zearalenone, alpha
      zearalenol (alpha-ZOL), beta-zearalenol, zearalanone, alpha-zeranol and, and beta
      zeranol. The method relies on three-step liquid-liquid extraction with ethyl
      acetate to eliminate the need for immunoaffinity extraction and minimize
      ionization matrix effects. Chromatographic separation of mycotoxins, including
      all isomers, was achieved with pentafluorophenyl column and water/methanol mobile
      phase. Mycotoxin detection and quantitation were performed using high-resolution
      mass spectrometry on LTQ Velos Orbitrap, in both positive and negative
      electrospray ionization (ESI(+) and (ESI(-)). The use of 0.02% acetic acid as
      mobile phase additive for ESI(-) resulted in significant increase in ionization
      efficiency ranging from 1.7 to 26 times for mycotoxins that ionize better in ESI(
      ). The optimized method was validated according to FDA guidance procedures. LOQs
      of all mycotoxins ranged from 0.1 to 0.5 ng/ml, except NIV which resulted in LOQ
      of 3 ng/ml because of low extraction recovery of this highly polar mycotoxin.
      Mean intra-day accuracy ranged from 85.8% to 116.4%, and intra-day precision (n =
      6) ranged from 1.6% to 12.5% RSD for all mycotoxins except alpha-ZOL where mean
      accuracy ranged from 72.9% to 97.2%. Inter-day accuracy and precision were 85.6%
      111.5% and 2.7-15.6% RSD respectively, showing good analytical performance of the
      method for biomonitoring.

PMID- 29576276
TI  - Liquid chromatography with alkylammonium formate ionic liquid mobile phases and
      fluorescence detection.
AB  - Fluorescence detection of various pharmaceuticals and the amino acid tryptophan
      (low molecular weight organic compounds) as well as the enzyme lactate
      dehydrogenase LDH (high molar mass compound) has been studied in aqueous
      solutions using alkyl ammonium formate ionic liquids as the primary solvent
      component. It was expected that the high viscosity of such ionic liquid-water
      mixtures would enhance fluorescence. Pharmaceuticals such as riboflavin and
      naproxen showed no such enhancement in the presence of ethylammonium formate
      (EAF) or isopropylammonium formate (IPAF) but the fluorescence of warfarin was
      substantially enhanced by a factor of 4 with 80% EAF and a factor of 7 with 70%
      IPAF. However, this improved fluorescence using alkylammonium formates did not
      seem to be general for other coumarin compounds except for bromadiolone which
      showed a similar fluorescence enhancement using EAF. Enhancement of tryptophan
      fluorescence was also seen for both EAF and IPAF. During the reversed phase
      elution of LDH on a polymeric HPLC column, remarkable enhancements in LDH peak
      intensity and activity were observed by incorporating 6% PEG 8000 in the organic
      mobile phase that contained either 20% acetonitrile or IPAF. Using higher
      concentrations of PEG 8000 is not recommended, not only because of the high
      viscosity, but also because the stabilizing effect of PEG 8000 is gradually
      reduced at higher concentrations.

PMID- 29576277
TI  - The clinicopathological and prognostic significance of PD-L1 expression in
      pancreatic cancer: A meta-analysis.
AB  - BACKGROUND: Immunotherapy has shown promise against solid tumors. However, the
      clinical significance of programmed cell death 1 (PD-1) and programmed cell death
      ligand 1 (PD-L1) in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This
      meta-analysis aimed to analyze the prognostic effect of PD-L1 in PDAC. DATA
      SOURCES: Electronic search of the PubMed, Cochrane Library and Web of Science was
      performed until December 2016. Through database searches, we identified articles
      describing the relationship between PD-L1 status and PDAC patient prognosis. Meta
      analysis was performed to investigate the relationship between PD-1 and overall
      survival (OS). RESULTS: Nine studies with 989 PDAC patients were included for PD
      L1 expression analysis. And 5 studies with 688 PDAC patients were included in the
      prognostic analysis. The PD-L1 positive rate measured by immunohistochemistry
      (IHC) was higher than that measured by polymerase chain reaction (PCR) (P <
      0.001). PDAC patients with high expression levels of PD-L1 had significantly
      reduced OS (HR = 2.34; 95% CI: 1.78-3.08). Subgroup analysis showed that the
      prognostic effect of PD-L1 levels was similar between the IHC and PCR methods.
      The PD-L1 positive rate was associated with PDAC T stages; the PD-L1 positive
      rate in the T3-4 group was higher than that in the T1-2 group (OR = 0.37; P =
      0.001). CONCLUSIONS: High PD-L1 expression levels predicted a poor prognosis in
      PDAC patients. Thus, PD-L1 status helps determine treatment in PDAC patients.

PMID- 29576278
TI  - A comparison of desensitization methods: Rituximab with/without plasmapheresis in
      ABO-incompatible living donor liver transplantation.
AB  - BACKGROUND: Plasmapheresis is a desensitization method used prior to ABO
      incompatible (ABO-I) living donor liver transplantation. However, studies on its
      usefulness in the rituximab era are lacking. METHODS: Fifty-six adult patients
      underwent ABO-I living donor liver transplantation between January 2012 and
      October 2015. A single dose of rituximab (300 mg/m2) was administered 2 weeks
      before surgery with plasmapheresis in all patients until February 2014 (RP group,
      n = 26). Patients were administered rituximab only, without plasmapheresis
      between March 2014 and October 2015 (RO group, n = 30). RESULTS: The 6-, 12- and
      18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and
      96.6%, 85.4% and 85.4% in the RO group, respectively (P = 0.574). When the
      initial isoagglutinin titers < 16, neither group showed a rebound rise of
      isoagglutinin titers. For patients with initial isoagglutinin titers >= 16, the
      rebound rise of isoagglutinin titers was more prominent in the RP group. There
      was no difference in time-dependent changes in B cell subpopulations and ABO-I
      related complications. CONCLUSIONS: Sufficient desensitization for ABO-I living
      donor liver transplantation can be achieved using rituximab alone. This
      desensitization strategy does not affect the isoagglutinin titers, ABO-I-related
      complications and patient survival.

PMID- 29576279
TI  - Prognostic factors and survival after surgical resection of pancreatic
      neuroendocrine tumor with validation of established and modified staging systems.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) display wide heterogeneity
      with highly variable prognosis. This study aimed to identify variables related to
      survival after surgical resection of PNET. METHODS: A total of 143 patients were
      identified from a prospectively maintained database. Patient characteristics were
      analyzed and prognostic factors for overall survival and progression-free
      survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to
      the cohort, and their ability to predict patient outcomes were compared. RESULTS:
      Multivariate analysis found that female gender, lymph node metastases and
      increasing WHO 2010 grade to be independently associated with reduced overall
      survival (P < 0.05). Patients requiring multi-visceral resection or debulking
      surgery found to be associated with shortest survival. ROC analysis found the
      ENETS and AJCC scoring systems to be similarly predictive of 5-year overall
      survival. Modified Ki67 significantly improved its accuracy in predicting 5-year
      overall survival (AUROC: 0.699 vs 0.605; P < 0.01). CONCLUSIONS: Multi-visceral
      or debulking surgery is associated with poor outcomes. There seems to be no
      significant difference between enucleation and anatomical segmental resection.
      Available scoring systems have reasonable accuracy in stratifying disease
      severity, with no system identified as being superior. Prognostic stratification
      with modified grading systems needs further validation before applied in clinical
      practice.

PMID- 29576280
TI  - Combination of tumor-associated regulatory T cell deletion and PD-1/PD-L1
      blockade: A promising immunotherapy for hepatocellular carcinoma?

PMID- 29576281
TI  - Public Health since the beginning: Neonatal incubators safety in a clinical
      setting.
AB  - BACKGROUND: The role of environmental cleaning as an effective measure to contain
      the diffusion of Healthcare Associated Infections (HAIs) has already been
      demonstrated. Among medical devices, neonatal incubators have been recognized as
      a source of pathogens involved in the spread of HAIs. Aim of the study was to
      assess the efficacy of a disinfection protocol for neonatal incubators. METHODS:
      The cross sectional study took place in the "Neonatal Pediatric Unit" of the
      Teaching Hospital of Siena: twenty incubators, used for critical newborns, were
      swabbed in 13 sampling points before and after the implementation of the
      disinfection protocol. Sanitation procedures were performed by trained staff,
      implementing the product Umonium38(r) Neutralis as disinfectant. Different
      culture media for the identification of the microbial contamination were adopted:
      plates were incubated for the proper time and the results were referred to Colony
      Forming Units (CFUs)/swab per point. Descriptive statistical analysis was
      performed. It was also evaluated the 95% confidence interval (C.I.) of the mean
      and the percentage of CFUs reduction by the bootstrap bias corrected and
      accelerated resampling method. RESULTS: Matched points analyzed were 313. The
      average CFUs percentage of reduction was 93.5% [C.I. 90.6-95.9%]: it was higher,
      97.0% [C.I. 94.1-99.1%], in points placed inside the incubators structure
      compared to the 88.4% [C.I. 83.6-93.0%] obtained outside. CONCLUSION: The
      disinfection protocol achieved good results. Routine surveillance and supervision
      of the various aspects of the disinfection processes (procedures, staff and
      disinfectants) could guarantee a safe environment during the first days of
      babies' life, avoiding harmful conditions for the newborns' health.

PMID- 29576282
TI  - Engineering nanoparticle strategies for effective cancer immunotherapy.
AB  - Cancer immunotherapy has been emerging in recent years, due to the inherent
      nature of the immune system. Although recent successes of immunotherapeutics in
      clinical application have attracted development of a novel immunotherapeutics,
      the off-target side effect and low immunogenicity of them remain challenges for
      the effective cancer immunotherapy. Theranostic nanoparticle system may one of
      key technology to address these issues by offering targeted delivery of various
      types of immunotherapeutics, resulting in significant improvements in the tumor
      immunotherapy. However, appropriate design or engineering of nanoparticles will
      be needed to improve delivery efficiency of antigen, adjuvant and therapeutics,
      resulting in eliciting antitumor immunity. Here, we review the current state of
      the art of cancer immunotherapeutic strategies, mainly based on nanoparticles
      (NPs). This includes NP-based antigen/adjuvant delivery vehicles to draining
      lymph nodes, and tumor antigen-specific T-lymphocytes for cancer immunotherapy.
      Several NP-based examples are shown for immune checkpoint modulation and
      immunogenic cell death. These overall studies demonstrate the great potential of
      NPs in cancer immunotherapy. Finally, engineering NP strategies will provide
      great opportunities to improve therapeutic effects as well as optimization of
      treatment processes, allowing to meet the individual needs in the cancer
      immunotherapy.

PMID- 29576283
TI  - Armed oncolytic viruses: A kick-start for anti-tumor immunity.
AB  - Oncolytic viruses (OVs), viruses that specifically result in killing tumor cells,
      represent a promising class of cancer therapy. Recently, the focus in the OV
      therapy field has shifted from their direct oncolytic effect to their immune
      stimulatory effect. OV therapy can function as a "kick start" for the antitumor
      immune response by releasing tumor associated antigens and release of
      inflammatory signals. Combining OVs with immune modulators could enhance the
      efficacy of both immune and OV therapies. Additionally, genetic engineering of
      OVs allows local expression of immune therapeutics, thereby reducing related
      toxicities. Different options to modify the tumor microenvironment in combination
      with OV therapy have been explored. The possibilities and obstacles of these
      combinations will be discussed in this review.

PMID- 29576284
TI  - Type I interferon and HIV: Subtle balance between antiviral activity,
      immunopathogenesis and the microbiome.
AB  - Type I interferon (IFN) response initially limits HIV-1 spread and may delay
      disease progression by stimulating several immune system components. Nonetheless,
      persistent exposure to type I IFN in the chronic phase of HIV-1 infection is
      associated with desensitization and/or detrimental immune activation, thereby
      hindering immune recovery and fostering viral persistence. This review provides a
      basis for understanding the complexity and function of IFN pleiotropic activity
      in HIV-1 infection. In particular, the dichotomous role of the IFN response in
      HIV-1 immunopathogenesis will be discussed, highlighting recent advances in the
      dynamic modulation of IFN production in acute versus chronic infection,
      expression signatures of IFN subtypes, and viral and host factors affecting the
      magnitude of IFN response during HIV-1 infection. Lastly, the review gives a
      forward-looking perspective on the interplay between microbiome compositions and
      IFN response.

PMID- 29576285
TI  - Real-World or Controlled Clinical Trial Data in Real-World Practice.

PMID- 29576286
TI  - Throwing More Cold Water on Heat Shock Protein 90 Inhibitors in NSCLC.

PMID- 29576287
TI  - Are We Ready to Safely Combine Anti-PD-1/PD-L1 with Cranial Irradiation in Non
      Small Cell Lung Cancer Patients?

PMID- 29576288
TI  - PD-(L)1 Inhibition and Cardiac Damage: A Relevant Toxicity?

PMID- 29576289
TI  - Erratum.

PMID- 29576290
TI  - Erratum.

PMID- 29576291
TI  - Increased Response Rates to Salvage Chemotherapy Administered after PD-1/PD-L1
      Inhibitors in Patients with Non-Small Cell Lung Cancer.

PMID- 29576292
TI  - Response to Costantini et al. "Comments on Increased Response Rates to Salvage
      Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non-Small
      Cell Lung Cancer".

PMID- 29576293
TI  - Comments on Prognostic Impact of Margin Distance and Tumor Spread through Air
      Spaces in Limited Resection for Primary Lung Cancer.

PMID- 29576294
TI  - Response to Letter to the Editor Titled "Comments on Prognostic Impact of Margin
      Distance and Tumor Spread through Air Spaces in Limited Resection for Primary
      Lung Cancer".

PMID- 29576295
TI  - Oligo-recurrence and Sync-oligometastases.

PMID- 29576296
TI  - Oligometastases.

PMID- 29576297
TI  - Response to Safri: "Comments on Comorbidity in Lung Cancer: A Prospective Cohort
      Study of Self-Reported versus Register-Based Comorbidity".

PMID- 29576298
TI  - Comments on Comorbidity in Lung Cancer: A Prospective Cohort Study of Self
      Reported versus Register-Based Comorbidity.

PMID- 29576299
TI  - Development of Complex Hepatic Cysts Is a Potential Side Effect of Crizotinib.

PMID- 29576300
TI  - National Cancer Database Report on Pneumonectomy Versus Lung-Sparing Surgery for
      Malignant Pleural Mesothelioma.

PMID- 29576301
TI  - Metformin and Lung Cancer: The Final Blow to the Obesity Paradox?

PMID- 29576302
TI  - Appearance of a BRAF Mutation Conferring Resistance to Crizotinib in Non-Small
      Cell Lung Cancer Harboring Oncogenic ROS1 Fusion.

PMID- 29576303
TI  - Neutralization effects of antibody elicited by chimeric HBV S antigen viral-like
      particles presenting HCV neutralization epitopes.
AB  - Hepatitis C virus (HCV) infection is a major public health problem despite
      effectual direct-acting antivirals (DAAs) therapy. Development of a prophylactic
      vaccine is essential to block spread of HCV infection. The HBV small surface
      antigen (HBsAg-S) can self-assemble into virus-like particles (VLPs), has higher
      immunogenicity and is used as a vaccine against HBV infections. Chimeric HBsAg-S
      proteins with foreign epitopes allow VLP formation and induce the specific
      humoral and cellular immune responses against the foreign proteins. In this
      study, we investigated the immune responses induced by chimeric VLPs with HCV
      neutralizing epitopes and HBV S antigen in mice. The chimeric HCV-HBV VLPs
      expressing neutralizing epitopes were prepared and purified. BALB/c mice were
      immunized with purified chimeric VLPs and the serum neutralizing antibodies were
      analyzed. We found that these chimeric VLPs induced neutralizing antibodies
      against HCV in mice. Additionally, the murine serum neutralized infections with
      HCV pseudoparticles and cell-cultured viruses derived from different heterologous
      1a, 1b and 2a genotypes. We also found that immunization with chimeric VLPs
      induced anti-HBsAg antibodies. This study provides a novel strategy for
      development of a HCV prophylactic neutralizing epitope vaccine and a HCV-HBV
      bivalent prophylactic vaccine.

PMID- 29576304
TI  - A phase III, open-label, randomised multicentre study to evaluate the
      immunogenicity and safety of a booster dose of two different reduced antigen
      diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with
      measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.
AB  - AIM: To evaluate the immunogenicity and safety of a reduced antigen diphtheria
      tetanus-acellular pertussis-inactivated poliovirus (dTap-IPVB) vaccine (Boostrix
      IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap
      IPVR (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella
      vaccine (MMRV). METHODS: This phase III, open label, randomised study was
      conducted in the UK between April 2011 and April 2012. Children due their pre
      school dTap-IPV booster vaccination were randomised 2:1 to receive one of two
      different dTap-IPV vaccines (dTap-IPVB or dTap-IPVR) with blood sample for
      immunogenicity assessment just prior and one month after vaccination. Immune
      responses to diphtheria, tetanus and polio antigens were compared between the
      study vaccines (inferential comparison). In the absence of an accepted pertussis
      correlate of protection, the immunogenicity of dTap-IPVB vaccine against
      pertussis was compared with historical pertussis efficacy data (inferential
      comparison). Safety and reactogenicity of both study vaccines were evaluated.
      RESULTS: 387 children were randomised and 385 vaccinated: 255 in the dTap-IPVB
      group and 130 in the dTap-IPVR group. Prior to vaccination, >=76.8% of children
      had anti-diphtheria and >=65.5% had anti-tetanus titres above the protection
      threshold; for pertussis, the pre-vaccination seropositivity rate ranged between
      18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children
      achieving titres above the pre-specified seroprotection/seropositivity
      thresholds. One serious adverse event not considered as causally related to the
      study vaccination by the study investigator was reported in the dTap-IPVB group.
      CONCLUSION: Non-inferiority of dTap-IPVB to dTap-IPVR was demonstrated. Both
      vaccines had a clinically acceptable safety and reactogenicity profile when co
      administered with MMRV to children 3-4 years old. TRIAL REGISTRATION: NCT01245049
      (ClinicalTrials.gov).

PMID- 29576305
TI  - A bibliometric analysis of systematic reviews on vaccines and immunisation.
AB  - INTRODUCTION: SYSVAC is an online bibliographic database of systematic reviews
      and systematic review protocols on vaccines and immunisation compiled by the
      London School of Hygiene & Tropical Medicine and hosted by the World Health
      Organization (WHO) through their National Immunization Technical Advisory Groups
      (NITAG) resource centre (www.nitag-resource.org). Here the development of the
      database and a bibliometric review of its content is presented, describing trends
      in the publication of policy-relevant systematic reviews on vaccines and
      immunisation from 2008 to 2016. MATERIALS AND METHODS: Searches were conducted in
      seven scientific databases according to a standardized search protocol, initially
      in 2014 with the most recent update in January 2017. Abstracts and titles were
      screened according to specific inclusion criteria. All included publications were
      coded into relevant categories based on a standardized protocol and subsequently
      analysed to look at trends in time, topic, area of focus, population and
      geographic location. RESULTS: After screening for inclusion criteria, 1285
      systematic reviews were included in the database. While in 2008 there were only
      34 systematic reviews on a vaccine-related topic, this increased to 322 in 2016.
      The most frequent pathogens/diseases studied were influenza, human papillomavirus
      and pneumococcus. There were several areas of duplication and overlap.
      DISCUSSION: As more systematic reviews are published it becomes increasingly time
      consuming for decision-makers to identify relevant information among the ever
      increasing volume available. The risk of duplication also increases, particularly
      given the current lack of coordination of systematic reviews on vaccine-related
      questions, both in terms of their commissioning and their execution. The SYSVAC
      database offers an accessible catalogue of vaccine-relevant systematic reviews
      with, where possible access or a link to the full-text. CONCLUSIONS: SYSVAC
      provides a freely searchable platform to identify existing vaccine-policy
      relevant systematic reviews. Systematic reviews will need to be assessed
      adequately for each specific question and quality.

PMID- 29576306
TI  - Porcine epidemic diarrhea vaccine efficacy evaluation by vaccination timing and
      frequencies.
AB  - Porcine epidemic diarrhea (PED) virus is a causative agent of enteric disease
      characterized by watery diarrhea and dehydration. Because PED has high morbidity
      and mortality, especially in suckling piglets, it causes a great economic loss to
      swine farms worldwide. Although various PED vaccines have been developed and
      commercialized, their efficacies are still controversial. In particular, current
      PED vaccination protocol (vaccination at 2 and 4 weeks before farrowing) may
      cause stress in pregnant sows. In this study, we compared the effects of PED
      vaccination timing and frequency for its efficacy by measuring the PED virus
      specific antibodies. We found that vaccination at early stages of pregnancy
      induces similar levels of serum and colostrum antibodies with those at late
      stages of pregnancy. As the number of vaccinations increased, the amounts of
      antibody in serum and colostrum, and neutralizing activities increased. Our
      results provide important information for establishing a more efficient PED
      vaccination protocol.

PMID- 29576307
TI  - Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid
      conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and
      adolescents: Results of a phase III, open, non-randomized study.
AB  - BACKGROUND: Individuals with functional or anatomic asplenia are at high risk for
      meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2
      doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid
      conjugate vaccine (MenACWY-TT) in this high-risk population. METHODS: This phase
      III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17
      year-olds with impaired splenic activity (high-risk group) and age-matched
      healthy controls (control group). We measured immune responses to MenACWY-TT by
      serum bactericidal activity assays using rabbit (rSBA) and human (hSBA)
      complement and in terms of antibodies against polysaccharides of the 4 vaccine
      serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from
      pre-vaccination levels or titers >=1:32 (rSBA)/>=1:8 (hSBA). We recorded
      solicited and unsolicited adverse events (AEs) during 4 and 31 days post
      vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs)
      throughout the study. RESULTS: The according-to-protocol cohort for
      immunogenicity included 40 participants per group. In both groups, the first
      MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across
      vaccine serogroups. Following the second MenACWY-TT dose, all participants had
      high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups.
      rSBA and hSBA geometric mean titers for each serogroup increased in both groups
      (with different magnitudes, but >=13.1-fold) compared with baseline levels.
      Polysaccharide antibody concentrations >=2.0 MUg/ml were detected in >=84.4% of
      participants and were similar between groups. Incidences of solicited and
      unsolicited AEs were comparable between groups. We recorded SAEs in 4/43
      participants in the high-risk group and 1/43 participants in the control group
      (none vaccine-related). No NOCIs were reported. CONCLUSION: In this descriptive
      study, MenACWY-TT induced similar functional and humoral immune responses and had
      a clinically acceptable safety profile in children and adolescents with impaired
      splenic activity and in healthy controls.

PMID- 29576308
TI  - A review of recommendations for rotavirus vaccination in Europe: Arguments for
      change.
AB  - BACKGROUND: More than 10 years after the authorisation of two rotavirus vaccines
      of demonstrated efficacy and with a strongly positive benefit-risk profile,
      uptake in Europe remains low. Only 13 countries in Europe provide a fully-funded
      rotavirus universal mass vaccination (UMV) programme, three provide a partially
      funded programme, and one provides full funding for a reduced programme targeting
      at-risk infants. Around 40% of countries in Europe currently have no existing
      recommendations for rotavirus vaccine use in children from the national
      government. METHODS: We provide an overview of the status of rotavirus vaccine
      recommendations across Europe and the factors impeding uptake. We consider the
      evidence for the benefits and risks of vaccination, and argue that cost
      effectiveness and cost-saving benefits justify greater access to rotavirus
      vaccines for infants living in Europe. RESULTS: Lack of awareness of the direct
      and indirect burden caused by rotavirus disease, potential cost-saving from
      rotavirus vaccination including considerable benefits to children, families and
      society, and government/insurer cost constraints all contribute to complacency at
      different levels of health policy in individual countries. CONCLUSIONS: More than
      10 years after their introduction, available data confirm the benefits and
      acceptable safety profile of infant rotavirus UMV programmes. Europe serves to
      gain considerably from rotavirus UMV in terms of reductions in healthcare
      resource utilization and related costs in both vaccinated subjects and their
      unvaccinated siblings through herd protection.

PMID- 29576309
TI  - Preventive effect of oral hangeshashinto (TJ-14) on the development of reflux
      induced esophageal cancer.
AB  - BACKGROUND: Prostaglandin E2 is one of the potential products that promotes
      development of tumors and also is a strong inducer of M2 phenotype macrophages,
      which contribute to tumor development in the immunosuppressed microenvironment.
      Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo medicine), has
      been reported to be effective in preventing chemotherapy-induced oral mucositis
      through the reduction of prostaglandin E2. We previously developed a surgical rat
      reflux model of esophageal cancer and used this well-established animal model to
      investigate the action of TJ-14 in preventing esophageal cancer. We also assessed
      the effect of TJ-14 on the downregulation of prostaglandin E2 production,
      utilizing esophageal squamous cell carcinoma cell line exposed to bile acid.
      METHODS: An end-to-side esophagojejunostomy was performed for the reflux model. A
      daily oral diet was subsequently administered, consisting of either diet
      incorporated TJ-14 or standard diet as a control group. The rats were killed at
      40 weeks after surgery. The incidence of esophageal cancer, Barrett's metaplasia,
      and proliferative hyperplasia were assessed histologically. CD163, a M2 phenotype
      macrophage marker, was assessed with immunohistochemistry. Prostaglandin E2
      enzyme immunoassay and lactate dehydrogenase assay were performed on
      chenodeoxycholic acid or gastroesophageal reflux contents exposed to esophageal
      squamous cell carcinoma cell line. RESULTS: Sixty-seven percent of the controls
      (n = 12) developed esophageal cancer, but animals that received TJ-14 (n = 10)
      had a cancer incidence of 10% (P=.007). Barrett's metaplasia was found in 83% of
      the rats in the control group and 50% of the rats in the TJ-14 indicating a
      protective tendency of TJ-14 (P=.095). All of the rats developed proliferative
      hyperplasia. The number of M2 phenotype macrophage were significantly decreased
      in the TJ-14 group compared to the control group in both Barrett's metaplasia and
      esophageal cancer lesions. TJ-14 inhibited chenodeoxycholic acid or
      gastroesophageal reflux content-induced prostaglandin E2 production in esophageal
      squamous cell carcinoma cell. CONCLUSION: TJ-14 reduced the incidence of reflux
      induced esophageal cancer and the infiltration of M2 macrophages in a surgical
      rat model or suppressed prostaglandin E2 production in esophageal squamous cell
      carcinoma cell. Further investigation is required regarding the potential
      clinical use of TJ-14 as an esophageal cancer chemopreventive agent.

PMID- 29576310
TI  - Controlled drug release to the inner ear: Concepts, materials, mechanisms, and
      performance.
AB  - Progress in drug delivery to the ear has been achieved over the last few years.
      This review illustrates the main mechanisms of controlled drug release and the
      resulting geometry- and size-dependent release kinetics. The potency,
      physicochemical properties, and stability of the drug molecules are key
      parameters for designing the most suitable drug delivery system. The most
      important drug delivery systems for the inner ear include solid foams, hydrogels,
      and different nanoscale drug delivery systems (e.g., nanoparticles, liposomes,
      lipid nanocapsules, polymersomes). Their main characteristics (i.e., general
      structure and materials) are discussed, with special attention given to
      underlining the link between the physicochemical properties (e.g., surface areas,
      glass transition temperature, microviscosity, size, and shape) and release
      kinetics. An appropriate characterization of the drug, the excipients used, and
      the formulated drug delivery systems is necessary to achieve a deeper
      understanding of the release process and decrease variability originating from
      the drug delivery system. This task cannot be solved by otologists alone. The
      interdisciplinary cooperation between otology/neurotology, pharmaceutics,
      physics, and other disciplines will result in improved drug delivery systems for
      the inner ear.

PMID- 29576311
TI  - Inter-joint coordination of kinematics and kinetics before and after total hip
      arthroplasty compared to asymptomatic subjects.
AB  - While differences in joint kinematics and kinetics between control subjects and
      patients before and after total hip arthroplasty (THA) has often been studied,
      inter-joint coordination has not been fully characterized. We hypothesized that
      in patients undergoing THA, inter-joint coordination (i) is different from
      control subjects before surgery, (ii) changes from pre-operative to post
      operative, and (iii) remains different from control subjects after surgery.
      Seventy-eight subjects underwent gait analysis before and ~1 year after primary
      unilateral THA. 109 control subjects were age, sex, and BMI matched to the THA
      group. We selected a representative trial at each subjects' self-selected walking
      speed from a motion analysis data repository. To assess kinematic coordination,
      we constructed sagittal plane hip-knee angle cyclograms, and calculated total,
      stance, and swing phase plot area (deg2). To assess kinetic coordination, we
      calculated the support moment (MS, %wt * ht), the time-integral of support moment
      (MS impulse, %wt * ht * t), and the relative contribution of each joint to MS
      impulse (%Hip, %Knee, %Ankle). We used t-tests to compare groups. Total and swing
      phase cyclogram area was smaller preoperatively, but improved to control values
      after THA. Swing-phase area was smaller than control values after THA. MS impulse
      was larger in THA subjects than controls both before and after surgery. While,
      the relative contribution of the hip to MS impulse was not different from control
      values, the contributions of the knee and ankle were smaller. Inter-joint
      coordination, as measured by hip-knee angle cyclograms and MS impulse, may be
      used to distinguish differences in gait mechanics between osteoarthritis and THA.
      Future work focusing on coordination among joints may be needed to fully restore
      gait function.

PMID- 29576312
TI  - Directional bias of soft-tissue artifacts on the acromion during recording of 3D
      scapular kinematics.
AB  - Scapular kinematics during sports performances can be recorded using skin-mounted
      trackers attached to the skin overlying the acromion for continuous data
      collection without restricting natural motions of the subject relative to medical
      imaging analyses limiting its use for wide-range or high-speed motions. This
      study aimed to describe the existence of a directional bias in the translational
      and rotational errors of skin-mounted trackers using a 3D magnetic resonance
      imaging (3D-MRI) protocol. 3D-MRI scans of the healthy right shoulders of 19
      males were acquired in 12 arm positions. The relative transformation of the
      scapular configuration determined to be the measurement error, as recorded by the
      configuration of the small cuboid imitating a skin-mounted tracker relative to
      the actual scapular configuration measured by the voxel-based registration. These
      measurement errors were expressed with either positive or negative values to
      describe the bias. Overall translational errors in the lateral, anterior, and
      superior directions were 3.7 +/- 8.4 mm, 9.5 +/- 6.4 mm, and 6.2 +/- 4.6 mm,
      respectively. Overall rotational errors in protraction, upward rotation, and
      posterior tilt were 7.8 +/- 8.4 degrees , 0.2 +/- 7.4 degrees , and - 4.0 +/- 7.5
      degrees , respectively. The skin-mounted tracker displayed a high probability of
      displacement in antero-superior (93% and 91%) directions and rotates in a
      protracting manner (82%) relative to the position of the underlying bone with the
      gradual nature of its change. The existence of the directional bias with its
      gradual change suggests a statistical predictability in measurement errors, which
      can be used to predict accurate scapular translation and rotation.

PMID- 29576313
TI  - Training induced changes in quadriceps activation during maximal eccentric
      contractions.
AB  - Despite full voluntary effort, neuromuscular activation of the quadriceps group
      of muscles appears inhibited during eccentric contractions. A nerve stimulation
      protocol during dynamic contractions of the quadriceps was developed that
      employed triplets of supramaximal pulses to assess suppressed eccentric
      activation. Subsequently the effects of a short training intervention, performed
      on a dynamometer, on eccentric strength output and neural inhibition were
      examined. Torque-angular velocity (T-omega) and experimental voluntary neural
      drive-angular velocity (%VA-omega; %VA, obtained via the interpolated twitch
      technique) datasets, were obtained from pre- and post-training testing sessions.
      Non-linear regression fits of a seven parameter torque function and of a 3rd
      degree polynomial were performed on the pre- and post-training T-omega and %VA
      omega datasets respectively. T-test showed a significant (p < 0.05) increase in
      the overall torque output post-training for the group, with three out of the six
      subjects demonstrating a significant (p < 0.05) increase in the torque output
      across the range of angular velocities as shown by the extra-sum-of-squares F
      test. A significant increase (p < 0.05) in the %VA post-training was also
      observed as well as a reduction in the plateauing of the torque output during
      fast eccentric contractions.

PMID- 29576314
TI  - Position of the quadriceps actuator influences knee loads during simulated squat
      testing.
AB  - The "Oxford Rig" cadaveric simulator permits researchers and clinicians to study
      knee mechanics during a simulated squatting motion. The motion of the lower limb
      in the Oxford Rig is typically controlled by a single actuator that applies
      tension to the quadriceps tendon. The location of the quadriceps actuator,
      however, has differed across published descriptions of the Oxford Rig. Actuators
      have been placed on the femur and pelvis, and on "grounded" locations external to
      the specimen, but the consequences of this placement for knee kinematics and
      kinetics are unknown. The purpose of this study was to examine these effects
      using a validated computational musculoskeletal model. When the actuator was
      placed on the femur or pelvis, forces realistically increased with knee flexion,
      with quadriceps and patellofemoral contact forces exceeding 2000 N and 3000 N,
      respectively, at 100 degrees  flexion. When the actuator was grounded, however,
      forces were substantially reduced and did not monotonically increase with
      flexion. Articular joint contact forces were not strongly influenced by changing
      the location of the actuator from the femur to the pelvis, with small RMS
      differences in quadriceps forces (48.2 N), patellofemoral forces (83.6 N), and
      tibiofemoral forces (58.9 N) between these conditions. The location of the
      actuator did not substantially affect knee kinematics. The results of this study
      suggest that the quadriceps actuator of the Oxford Rig should be attached to
      either the femur or the pelvis when the goal is to make realistic estimates of
      quadriceps forces and articular contact forces within the knee joint.

PMID- 29576316
TI  - Glycosylation in cancer: Selected roles in tumour progression, immune modulation
      and metastasis.
AB  - Tumour metastasis is the main cause of cancer related deaths. Metastasis is an
      intricate multi-step process that requires the acquisition of several cancer cell
      features, including the modulation of tumour cell migration, adhesion, invasion,
      and immune evasion. Changes in the cellular glycosylation are associated with
      malignant transformation of cancer cells, tumour progression and ultimately,
      metastasis formation. Glycans have major impact on cellular signalling and on the
      regulation of tumour cell-cell adhesion and cell-matrix interaction. Glycans
      drive the interplay between the cancer cells and the tumour microenvironment. In
      this review, we summarize the roles of glycan alterations in tumour progression,
      such as acquisition of oncogenic features due to modulation of receptor tyrosine
      kinases, proteoglycans, cadherins and integrins. We also highlight the importance
      of key glycan binding proteins such as selectins, siglecs and galectins, which
      are pivotal in the modulation of immune response. An overview on glycans as
      cancer biomarkers is also presented.

PMID- 29576315
TI  - Liver induced transgene tolerance with AAV vectors.
AB  - Immune tolerance is a vital component of immunity, as persistent activation of
      immune cells causes significant tissue damage and loss of tolerance leads to
      autoimmunity. Likewise, unwanted immune responses can occur in inherited
      disorders, such as hemophilia and Pompe disease, in which patients lack any
      expression of protein, during treatment with enzyme replacement therapy, or gene
      therapy. While the liver has long been known as being tolerogenic, it was only
      recently appreciated in the last decade that liver directed adeno-associated
      virus (AAV) gene therapy can induce systemic tolerance to a transgene. In this
      review, we look at the mechanisms behind liver induced tolerance, discuss
      different factors influencing successful tolerance induction with AAV, and
      applications where AAV mediated tolerance may be helpful.

PMID- 29576317
TI  - Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of
      Autoinhibition.
AB  - Pyroptosis is an inflammatory form of programmed cell death that plays important
      roles in immune protection against infections and in inflammatory disorders.
      Gasdermin D (GSDMD) is an executor of pyroptosis upon cleavage by caspases
      1/4/5/11 following canonical and noncanonical inflammasome activation. GSDMD N
      terminal domain assembles membrane pores to induce cytolysis, whereas its C
      terminal domain inhibits cell death through intramolecular association with the N
      domain. The molecular mechanisms of autoinhibition for GSDMD are poorly
      characterized. Here we report the crystal structures of the human and murine
      GSDMD C-terminal domains, which differ from those of the full-length murine
      GSDMA3 and the human GSDMB C-terminal domain. Mutations of GSDMD C-domain
      residues predicted to locate at its interface with the N-domain enhanced
      pyroptosis. Our results suggest that GSDMDs may employ a distinct mode of
      intramolecular domain interaction and autoinhibition, which may be relevant to
      its unique role in pyroptosis downstream of inflammasome activation.

PMID- 29576318
TI  - A Structural Model of the Urease Activation Complex Derived from Ion Mobility
      Mass Spectrometry and Integrative Modeling.
AB  - The synthesis of active Klebsiella aerogenes urease via an 18-subunit enzyme
      apoprotein-accessory protein pre-activation complex has been well studied
      biochemically, but thus far this complex has remained refractory to direct
      structural characterization. Using ion mobility-mass spectrometry, we
      characterized several protein complexes between the core urease apoprotein and
      its accessory proteins, including the 610-kDa (UreABC)3(UreDFG)3 complex. Using
      our recently developed computational modeling workflow, we generated ensembles of
      putative (UreABC)3(UreDFG)3 species consistent with experimental restraints and
      characterized the structural ambiguity present in these models. By integrating
      structural information from previous studies, we increased the resolution of the
      ion mobility-mass spectrometry-derived models substantially, and we observe a
      discrete population of structures consistent with all of the available data for
      this complex.

PMID- 29576319
TI  - Structure-Function Relationship of the Bik1-Bim1 Complex.
AB  - In budding yeast, the microtubule plus-end tracking proteins Bik1 (CLIP-170) and
      Bim1 (EB1) form a complex that interacts with partners involved in spindle
      positioning, including Stu2 and Kar9. Here, we show that the CAP-Gly and coiled
      coil domains of Bik1 interact with the C-terminal ETF peptide of Bim1 and the C
      terminal tail region of Stu2, respectively. The crystal structures of the CAP-Gly
      domain of Bik1 (Bik1CG) alone and in complex with an ETF peptide revealed unique,
      functionally relevant CAP-Gly elements, establishing Bik1CG as a specific C
      terminal phenylalanine recognition domain. Unlike the mammalian CLIP-170-EB1
      complex, Bik1-Bim1 forms ternary complexes with the EB1-binding motifs SxIP and
      LxxPTPh, which are present in diverse proteins, including Kar9. Perturbation of
      the Bik1-Bim1 interaction in vivo affected Bik1 localization and astral
      microtubule length. Our results provide insight into the role of the Bik1-Bim1
      interaction for cell division, and demonstrate that the CLIP-170-EB1 module is
      evolutionarily flexible.

PMID- 29576320
TI  - The Helix Rearrangement in the Periplasmic Domain of the Flagellar Stator B
      Subunit Activates Peptidoglycan Binding and Ion Influx.
AB  - The stator of the bacterial flagellar motor couples ion flow with torque
      generation. The ion-conducting stator channel opens only when incorporated into
      and anchored around the rotor via the peptidoglycan (PG) binding domain of the B
      subunit (MotBC). However, no direct evidence of PG binding coupled with channel
      activation has been presented. Here, we report the structural rearrangements of
      MotBC responsible for this coupling process. A MotBC fragment with the L119P
      replacement, which is known to cause channel activation, was able to bind PG.
      Nuclear magnetic resonance analysis of MotBC and the crystal structure of the
      MotBC-L119P dimer revealed major structural changes in helix alpha1. In vivo
      crosslinking results confirm that a major rearrangement occurs. Our results
      suggest that, upon stator incorporation into the motor, helix alpha1 of MotBC
      changes into an extended non-helical structure. We propose that this change
      allows the stator both to bind PG and to open its proton channel.

PMID- 29576321
TI  - An Intracellular Allosteric Modulator Binding Pocket in SK2 Ion Channels Is
      Shared by Multiple Chemotypes.
AB  - Small conductance potassium (SK) ion channels define neuronal firing rates by
      conducting the after-hyperpolarization current. They are key targets in
      developing therapies where neuronal firing rates are dysfunctional, such as in
      epilepsy, Parkinson's, and amyotrophic lateral sclerosis (ALS). Here, we
      characterize a binding pocket situated at the intracellular interface of SK2 and
      calmodulin, which we show to be shared by multiple small-molecule chemotypes.
      Crystallization of this complex revealed that riluzole (approved for ALS) and an
      analog of the anti-ataxic agent (4-chloro-phenyl)-[2-(3,5-dimethyl-pyrazol-1-yl)
      pyrimidin-4-yl]-amine (CyPPA) bind to and allosterically modulate via this site.
      Solution-state nuclear magnetic resonance demonstrates that riluzole, NS309, and
      CyPPA analogs bind at this bipartite pocket. We demonstrate, by patch-clamp
      electrophysiology, that both classes of ligand interact with overlapping but
      distinct residues within this pocket. These data define a clinically important
      site, laying the foundations for further studies of the mechanism of action of
      riluzole and related molecules.

PMID- 29576322
TI  - Evidence for association of STAT4 and IL12RB2 variants with Myasthenia gravis
      susceptibility: What is the effect on gene expression in thymus?
AB  - Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of
      autoantibodies that bind mainly to the acetylcholine receptor (AChR) in the
      neuromuscular junction. In our case-control association study, we analyzed common
      variants located in genes of the IL12/STAT4 and IL10/STAT3 signaling pathways. A
      total of 175 sporadic MG patients of Greek descent, positively detected with anti
      AChR autoantibodies and 84 ethnically-matched, healthy volunteers were enrolled
      in the study. Thymus samples were obtained from 16 non-MG individuals for
      relative gene expression analysis. The strongest signals of association were
      observed in the cases of rs6679356 between the late-onset MG patients and
      controls and rs7574865 between early-onset MG and controls. Our investigation of
      the correlation between the MG-associated variants and the expression levels of
      each gene in thymus did not result in significant differences.

PMID- 29576323
TI  - Immunomodulatory treatment with systemic GM-CSF augments pulmonary immune
      responses and improves neurological outcome after experimental stroke.
AB  - Stroke-induced immunodepression is an independent risk factor for stroke
      associated pneumonia (SAP). Granulocyte-macrophage colony stimulating factor (GM
      CSF) has neuroprotective properties in experimental stroke and been demonstrated
      to reverse immunodepression in sepsis patients. However, whether GM-CSF restores
      immune function after stroke preventing SAP and improving outcome is unknown.
      Here, we demonstrated that GM-CSF treatment improved peripheral and pulmonary
      leukocyte numbers, peripheral cytokine responses, lowered lung bacterial burden
      in the early course and improved long-term functional outcome after experimental
      stroke. These data suggest that GM-CSF is promising for stroke treatment since it
      not only acts neuroprotective in the ischemic brain but may also protect against
      detrimental post-stroke infections.

PMID- 29576324
TI  - Prevalence of Nail Scabies: A French Prospective Multicenter Study.
AB  - INTRODUCTION: To assess the prevalence of nail involvement in children <16 years
      old with a confirmed diagnosis of scabies. STUDY DESIGN: Observational,
      prospective study in 7 French dermatology departments between June 2015 and
      January 2017. Children were included if they had scabies confirmed by dermoscopy
      and/or microscopy and if nails could be sampled. The first toenails and
      thumbnails as well as clinically affected nails were systematically sampled for
      microscopic examination. Individual data were recorded via a standardized
      questionnaire. RESULTS: A total of 47 children with scabies were included (26
      females [55.3%], mean age 3.6 +/- 4.0 years). Pruritus was present in 42 children
      (89.3%); the relapse rate was 38.3% (n = 18). In 3 infants (6.4%), Sarcoptes
      mites were revealed by dermoscopy or microscopy of the first toenails (2 cases)
      and a thumbnail (1 case), but nails were normal in 2 children. Two of the 3
      infants had already received treatment for scabies in the previous weeks.
      CONCLUSION: Prevalence of nail involvement in children with confirmed scabies was
      6.4%. Nails should not be overlooked during scabies treatment.

PMID- 29576325
TI  - Adjunct Targeted Biologic Inhibition Agents to Treat Aggressive Multivessel
      Intraluminal Pediatric Pulmonary Vein Stenosis.
AB  - OBJECTIVE: To evaluate the use of imatinib mesylate with or without bevacizumab
      targeting neoproliferative myofibroblast-like cells with tyrosine kinase receptor
      expression, as adjuncts to modern interventional therapies for the treatment of
      multivessel intraluminal pulmonary vein stenosis (PVS). We describe the 48- and
      72-week outcomes among patients receiving imatinib mesylate with or without
      bevacizumab for multivessel intraluminal PVS. STUDY DESIGN: This single-arm,
      prospective, open-label US Food and Drug Administration approved trial enrolled
      patients with >=2 affected pulmonary veins after surgical or catheter-based
      relief of obstruction between March 2009 and December 2014. Drug therapy was
      discontinued at 48 weeks, or after 24 weeks of stabilization, whichever occurred
      later. RESULTS: Among 48 enrolled patients, 5 had isolated PVS, 26 congenital
      heart disease, 5 lung disease, and 12 both. After the 72-week follow-up, 16
      patients had stabilized, 27 had recurred locally without stabilization, and 5 had
      progressed. Stabilization was associated with the absence of lung disease (P =
      .03), a higher percentage of eligible drug doses received (P = .03), and was not
      associated with age, diagnosis, disease laterality, or number of veins involved.
      Survival to 72 weeks was 77% (37 of 48). Adverse events were common (n = 1489
      total), but only 16 were definitely related to drug treatment, none of which were
      serious. CONCLUSION: Survival to 72 weeks was 77% in a referral population with
      multivessel intraluminal PVS undergoing multimodal treatment, including
      antiproliferative tyrosine kinase blockade. Toxicity specific to tyrosine kinase
      blockade was minimal.

PMID- 29576326
TI  - Remission in CBT for adult anxiety disorders: A meta-analysis.
AB  - Currently there is no universally accepted definition of remission in anxiety
      disorders. This may be causing significantly different estimates of treatment
      efficacy across anxiety disorders. The aim of this paper was to determine not
      only the overall remission rate in cognitive-behavioral therapy (CBT) for anxiety
      disorders, but also to examine whether the different definitions of remission
      lead to significantly different remission rates. From the initial 228 abstracts
      reviewed by the authors, 100 articles were retained. The overall mean remission
      rate was 51.0%. Remission rates were highest when remission was defined as good
      end state functioning or no longer meeting criteria for the primary diagnosis.
      Studies of posttraumatic stress disorder had the highest remission rates, while
      those of obsessive-compulsive disorder and social anxiety disorder had the lowest
      remission rates. Rates of remission differed by certain demographic (e.g., older
      age) and clinical (e.g., medication use) characteristics. Although CBT is an
      empirically supported treatment for anxiety disorders, it is clear that there is
      room for improvement, as many patients do not achieve remission status.

PMID- 29576327
TI  - Parental mosaicism in RYR1-related Central Core Disease.
AB  - Myopathies due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene
      are amongst the most common non-dystrophic neuromuscular disorders and have been
      associated with both dominant and recessive inheritance. Several cases with
      apparently de novo dominant inheritance have been reported. Here we report two
      siblings with features of Central Core Disease (CCD) born to unaffected parents.
      Genetic testing revealed a heterozygous dominant RYR1 c.14582G>A (p. Arg4861His)
      mutation previously identified in other CCD pedigrees. The variant was absent in
      blood from the asymptomatic mother but detected at low but variable levels in
      blood- and saliva-derived DNA from the unaffected father, suggesting that this
      mutation has arisen as a paternal post-zygotic de novo event. These findings
      suggest that parental mosaicism should be considered in RYR1-related myopathies,
      and may provide one possible explanation for the marked intergenerational
      variability seen in some RYR1 pedigrees.

PMID- 29576328
TI  - Mitophagy: A Mechanism for Plant Growth and Survival.
AB  - Mitophagy is a conserved cellular process that is important for autophagic
      removal of damaged mitochondria to maintain a healthy mitochondrial population.
      Mitophagy also appears to occur in plants and has roles in development, stress
      response, senescence, and programmed cell death. However, many of the genes that
      control mitophagy in yeast and animal cells are absent from plants, and no plant
      proteins marking defunct mitochondria for autophagic degradation are yet known.
      New insights implicate general autophagy-related proteins in mitophagy, affecting
      the senescence of plant tissues. Mitophagy control and its importance for energy
      metabolism, survival, signaling, and cell death in plants are discussed.
      Furthermore, we suggest mitochondrial membrane proteins containing ATG8
      interacting motifs, which might serve as mitophagy receptor proteins in plant
      mitochondria.

PMID- 29576329
TI  - Climate Change and Insect Pests: Resistance Is Not Futile?
AB  - Chemical signals produced by plants when attacked by herbivores play a crucial
      role in efficient plant defence. A recent study suggests that herbivore-specific
      R-gene resistance may be enhanced by elevated atmospheric CO2 concentrations.
      Understanding how climate change affects plant resistance to herbivorous pests
      could be essential for future food security.

PMID- 29576331
TI  - [Punctal agenesis with fusion of the two canaliculi: A very rare congenital
      malformation].

PMID- 29576330
TI  - Intralacrimal migration of Masterka(r) stents.
AB  - BACKGROUND: Tearing and conjunctivitis in children are commonly due to lacrimal
      drainage system obstruction. Congenital nasolacrimal obstruction is a common
      pathology treated by probing with or without silicone stent insertion, depending
      upon the age of the child. The silicone stent is self-retaining and placed for at
      least one month. Masterka(r) is a recent version of Monoka(r), which may lead to
      the same surgical complications, such as intralacrimal migration. SUBJECTS AND
      METHODS: The medical records of two patients surgically treated with the
      Masterka(r) probe for nasolacrimal duct obstruction, who developed intralacrimal
      migration of the stent, were retrospectively reviewed and analyzed. A 41-month
      old child and an 18-month-old child presented with disappearance of the silicone
      tube after 7 days and 2 years respectively. In the first case, the tube migrated
      completely within the lacrimal system and became externalized through the nose at
      2 years, while in the second case, the Masterka(r) was retrieved through a
      canalicular approach. In both cases, infants had no further tearing. DISCUSSION:
      The frequency self-retaining stent disappearance is estimated at 15%. Among these
      cases, intralacrimal migration is only reported in 0.5% of cases. To prevent
      intralacrimal migration, the surgical technique must follow a certain number of
      rules. Management, based on residual epiphora, is discussed. CONCLUSION:
      Prevention of intralacrimal migration of self-retaining stents involves a
      rigorous analysis of the relationship between the meatus and the fixation head at
      the time of placement. After lacrimal intubation, scheduled monitoring is
      necessary to screen for stent disappearance. Management is based on clinical
      findings, anterior rhinoscopy and even exploratory canaliculotomy.

PMID- 29576332
TI  - Ultrasound-guided embryo transfer: summary of the evidence and new perspectives.
      A systematic review and meta-analysis.
AB  - Despite the purported advantages of ultrasound guidance during embryo transfer,
      and the large number of clinical trials published on this topic, recommendations
      for the use of this technique in daily clinical practice are still under debate.
      We designed a meta-analysis based exclusively on evidence from published
      randomized controlled trials, with the aim of analysing the effect of trans
      abdominal ultrasound guidance during embryo transfer versus clinical touch and of
      transvaginal ultrasound guidance (TV-US) versus the trans-abdominal approach on
      IVF outcomes. On the basis of 14 randomized trials, we found a moderate quality
      of evidence supporting the beneficial effects of transabdominal guidance during
      embryo transfer compared with conventional clinical touch in clinical pregnancy
      and ongoing or live birth rates. No significant differences were found in
      miscarriage and ectopic pregnancy rate, with low or very low quality of evidence,
      respectively. On the basis of three randomized trials, we found the quality of
      evidence supporting the equivalence of transvaginal versus transabdominal
      approach in clinical pregnancy and ongoing or live birth rates to be low.
      Finally, larger randomized controlled trials are necessary to explore the
      possible benefits of TV-US, three-dimensional ultrasound imaging modality, and
      uterine length measurement before transfer.

PMID- 29576333
TI  - Enhancing Participation in Cardiac Rehabilitation: A Question of Proximity and
      Integration of Outpatient Services.
AB  - Numerous investigations have established the strong clinical utility of cardiac
      rehabilitation, while clinical guidelines continually call for a high level of
      referral and participation. Historically, medical facilities have faced
      challenges referring eligible patients to cardiac rehabilitation, enrolling only
      a small portion of those receiving referral. Consequently, less than ~10% of
      qualifying patients receive any amount of cardiac rehabilitation. This sobering
      figure has prompted many efforts to identify barriers to referral as well as
      enrollment and accordingly propose strategies to bolster participation rates.
      Although reports have highlighted improvements through focused approaches,
      enrollment rates still lag behind the goal of reaching 70% by 2022, proposed by
      the Million Hearts Cardiac Rehabilitation Collaborative. An area of inquiry that
      has received little to no attention in this effort has been the influence of
      proximity between physician-driven outpatient clinics and cardiac rehabilitation
      facilities. In this report we outline the development and design of a clinical
      faculty practice aimed to maintainclose geographical proximity between our
      physicianclinic and the cardiac rehabilitation area. We also propose that our
      impressive enrollment rates of 57% within our facility and 73% when including
      patients that started alternative exercise programs were likely due to
      establishing a close proximity between the respective practices.

PMID- 29576334
TI  - A cost-effectiveness analysis of lowering residential radon levels in Sweden
      Results from a modelling study.
AB  - PURPOSE: Residential exposure to radon is considered as the second leading cause
      of lung cancer after smoking. The purpose of this study was to conduct a cost
      effectiveness analysis of reducing the indoor radon levels in Sweden from the
      current reference level of 200 Bq/m3 to the WHO suggested reference level of
      maximum 100 Bq/m3. METHODS: We constructed a decision-analytic cost-effectiveness
      model using input data from published literature and administrative records. The
      model compared the increase in economic costs to the health benefits of lower
      indoor radon-levels in a Swedish policy context. We estimated the cost per life
      year and quality adjusted life year (QALY) gained and assessed the robustness of
      the results using both deterministic and probabilistic sensitivity analysis.
      RESULTS: Including (excluding) costs of added life years the cost per QALY for
      existing homes was ?130,000 (?99,000). For new homes the cost per QALY including
      (excluding) costs of added life years was ?39,000 (?25,000). CONCLUSIONS: The
      results indicate that it is not cost-effective to reduce indoor radon levels from
      200 Bq/m3 to a maximum of 100 Bq/m3 in existing homes, whereas it is cost
      effective for new homes.

PMID- 29576335
TI  - Limited Adherence to Peripheral Arterial Disease Guidelines and Suboptimal Ankle
      Brachial Index Reliability in Dutch Primary Care.
AB  - OBJECTIVE/BACKGROUND: The Dutch College of General Practitioners' guideline on
      peripheral arterial disease (PAD) provides clear recommendations on the
      management of PAD. An ankle brachial index (ABI) measurement, prescription of
      antiplatelet drugs and statins, and supervised exercise therapy (SET) for
      intermittent claudication (IC) are advised. The aims of this study were to
      determine the adherence of general practitioners (GPs) to their own guideline on
      PAD and to evaluate the reliability of primary care ABI measurements. METHODS:
      This was a cross-sectional study. All patients suspected of having symptomatic
      PAD who were referred by GPs to a large hospital in 2015 were evaluated regarding
      three of the guideline criteria: (i) ABI measurement; (ii) prescription of
      secondary prevention; (iii) initiation of SET. ABI values obtained in primary
      care and the hospital's vascular laboratory were compared using correlation
      coefficients and regression analysis. An abnormal ABI was defined as a value <.9
      (normal ABI >=.9). RESULTS: Of 308 potential patients with new onset PAD, 58% (n
      = 178) had undergone ABI measurement prior to referral. A modest correlation
      between ABI values obtained in primary care and the vascular laboratory was found
      (r = .63, p < .001). Furthermore, a moderate reliability was calculated
      (intraclass correlation coefficient 0.60, 95% confidence interval 0.49-0.69, p <
      .001). Of the new patients with an abnormal ABI, 59% used antiplatelet drugs and
      55% used statins. A referral for SET was initiated by a GP in 10% of new PAD
      patients with IC symptoms. CONCLUSIONS: Adherence by Dutch GPs to their own
      society's PAD guideline has room for improvement. The reliability of ABI
      measurements is suboptimal, whereas rates of prescription of secondary prevention
      and initiation of SET as primary treatment for IC need upgrading.

PMID- 29576336
TI  - The Impact of Suprarenal Fixation on Renal Function Following Endovascular
      Abdominal Aortic Aneurysm Repair: Meta-analysis Based on Estimated Glomerular
      Filtration Rate.
AB  - BACKGROUND: Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) is
      currently used routinely to treat AAA. Suprarenal fixation (SRF) of EVAR grafts
      can lead to renal dysfunction. A meta-analysis of studies using estimated
      glomerular filtration rate (eGFR) as a measure of renal injury to assess the
      effect of SRF on renal function was performed. METHODS: An electronic search was
      carried out to identify all articles that reported on renal injury following SRF
      versus infrarenal fixation (IRF) EVAR, and 24 studies were identified. Formal
      meta-analysis was used to assess eGFR drop at 1 and 5 years. The primary outcome
      measure was a drop in eGFR >20% at 1 year; secondary measures included eGFR drop
      >20% at 5 years and "renal dysfunction" based on the definition used in each
      publication. RESULTS: Five series reported eGFR reduction >20% at 1 year. The
      weighted odds ratio (OR) was 1.53 (95% CI 0.67-3.51, p = .31, I2 = 53.2%); 9.3%
      for SRF versus 7.4% for IRF. One study reported eGFR based renal dysfunction at 5
      years: OR 1.77 (95% CI 1.04-3.02, p = .03); 16.9% for SRF versus 10.3% for IRF.
      Nineteen series reported some form of renal dysfunction (5287 SRF vs. 4386 IRF
      patients, mean follow up: 20.5 months, range 72 h to 5 years). The weighted OR
      was 1.32 (95% CI 1.01-1.71, p = .03, I2 = 28.4%); 5.1% for SRF versus 4.6% for
      IRF. "Renal dysfunction" definitions varied greatly and were based on creatinine
      or other inaccurate methods. CONCLUSION: EVAR using SRF does not lead to a
      significant drop in renal function at 1 year, based on eGFR. Long-term results
      are limited. Authors should report long-term renal injury using eGFR and not
      inaccurate arbitrary measures, which are currently common in the literature.

PMID- 29576337
TI  - A Feasibility Study of a New Unibody Branched Stent Graft Applied to Reconstruct
      the Canine Aortic Arch.
AB  - OBJECTIVES: The aim was to evaluate the feasibility and safety of a new unibody
      branched stent graft for the reconstruction of the canine aortic arch. METHODS:
      The unibody branched stent grafts included single branched stent grafts and
      double branched stent grafts. The main stent graft and branched limbs were
      sutured together. The branched stent grafts were folded into the introducer
      system, which consisted of a double channel catheter, a detachable sleeve, and an
      introducer sheath. The branched stent grafts were introduced and deployed into
      the aortic arch by the delivery system. Twenty adult mongrel dogs were used for
      the experiments. Ten dogs were implanted with single branched stent grafts; the
      other 10 were implanted with double branched stent grafts. The surviving animals
      were followed up for 3 months. Computed tomography angiography (CTA) was
      performed to observe the status of the branched stent grafts. RESULTS: All the
      unibody branched stent grafts were successfully implanted into the canine aortic
      arches. The technical success rate was 100%. There was no cerebral infarction,
      paraplegia or incision infection. CTA showed that all the branched stent grafts
      were patent; there was no endoleak or stent migration. CONCLUSIONS: The unibody
      branched stent graft system could be used to reconstruct the aortic arch. The
      animal experimental procedures demonstrated the safety and feasibility of the
      unibody branched stent graft system.

PMID- 29576338
TI  - Following ulnar collateral ligament reconstruction, professional baseball
      position players return to play faster than pitchers, but catchers return less
      frequently.
AB  - BACKGROUND: Although much as been done to characterize trends of medial ulnar
      collateral ligament (UCL) reconstruction in pitchers, outcomes in position
      players (PPs) (non-pitchers) remain undefined in the current literature. METHODS:
      Three resources were combined to identify all known Major League Baseball and
      Minor League Baseball (MiLB) PPs who have ever undergone UCL reconstruction. A
      multitude of player and surgical variables were included. Trends over time were
      analyzed collectively, based on level of play, revision status (primary vs
      revision), and position. Additional comparisons were made with a known cohort of
      professional baseball pitchers having undergone UCL reconstruction. RESULTS: We
      identified 168 UCL reconstructions in professional PPs. The annual rate of
      primary UCL reconstruction rose significantly from 1984 to 2015 (P < .001), and
      the proportion of cases performed in MiLB PPs (vs Major League Baseball PPs)
      increased steadily (P < .001). Of PPs, 75.5% returned to play at any level at a
      mean of 342 days. Catchers demonstrated the lowest return-to-play (RTP) rate
      (58.6%) compared with infielders (75.6%) and outfielders (88.9%). The overall
      revision rate was low, at 4.8%. Compared with pitchers, PPs demonstrated a lower
      rate of RTP (75.5% for PPs vs 83.7% for pitchers, P = .040) but shorter RTP times
      for those able to return (342 days for PPs vs 435 days for pitchers, P < .001).
      CONCLUSIONS: The incidence of UCL reconstruction in PPs continues to rise, a
      trend that is significantly more pronounced at the MiLB level. Although PPs
      (particularly catchers) are less likely to return to professional baseball
      compared with pitchers, those who are able to RTP do so more rapidly.

PMID- 29576339
TI  - Early return to baseline range of motion and strength after anterior shoulder
      instability surgery: a Multicenter Orthopaedic Outcomes Network (MOON) shoulder
      group cohort study.
AB  - BACKGROUND: Patients often return to higher-level activities and sports at 4 to 8
      months after anterior shoulder stabilization procedures. It is unknown what
      percentage of patients have regained normal function at this time frame and what
      factors predict residual deficits, range of motion (ROM), and strength after
      anterior shoulder instability surgery. METHODS: Ten participating sites
      throughout the United States enrolled patients in a prospective cohort study
      including primary, revision, arthroscopic, and open anterior stabilization
      procedures. Baseline demographic data and patient outcomes questionnaires were
      collected with initial physical examination, treatment, surgical findings, and
      surgical repair details. At the 6-month follow-up visit, ROM and strength
      measurements were collected and compared with preoperative measurements. RESULTS:
      There were 348 patients identified who underwent surgical treatment for anterior
      shoulder instability. Of these, 259 patients (74.0%) returned to baseline, and 89
      (26.0%) did not return to baseline shoulder ROM (>=20 degrees  loss of ROM) or
      strength. A higher Beighton score (P = .01) and number of dislocations (P < .01)
      were associated with failure to regain baseline ROM and strength at early follow
      up. No surgical variables were found to influence return to baseline function,
      including open vs. arthroscopic surgery, primary vs. revision surgery, and number
      of suture anchors. CONCLUSIONS: By 4 to 8 months postoperatively, 76% of patients
      return to baseline ROM, 98% return to baseline strength, and 74% return to both
      baseline ROM and strength. An increased number of dislocations and generalized
      joint laxity were associated with failure to return to baseline ROM and strength
      at early follow-up after anterior shoulder instability surgery.

PMID- 29576340
TI  - Superior glenoid inclination and rotator cuff tears.
AB  - BACKGROUND: The objectives of this study were to determine whether glenoid
      inclination (1) could be measured accurately on magnetic resonance imaging (MRI)
      using computed tomography (CT) as a gold standard, (2) could be measured reliably
      on MRI, and (3) whether it differed between patients with rotator cuff tears and
      age-matched controls without evidence of rotator cuff tears or glenohumeral
      osteoarthritis. METHODS: In this comparative retrospective radiographic study, we
      measured glenoid inclination on T1 coronal MRI corrected into the plane of the
      scapula. We determined accuracy by comparison with CT and inter-rater
      reliability. We compared glenoid inclination between patients with full-thickness
      rotator cuff tears and patients aged >50 years without evidence of a rotator cuff
      tear or glenohumeral arthritis. An a priori power analysis determined adequate
      power to detect a 2 degrees  difference in glenoid inclination. RESULTS: (1) In a
      validation cohort of 37 patients with MRI and CT, the intraclass correlation
      coefficient was 0.877, with a mean difference of 0 degrees  (95% confidence
      interval, -1 degrees  to 1 degrees ). (2) For MRI inclination, the inter-rater
      intraclass correlation coefficient was 0.911. (3) Superior glenoid inclination
      was 2 degrees  higher (range, 1 degrees -4 degrees , P < .001) in the rotator
      cuff tear group of 192 patients than in the control cohort of 107 patients.
      CONCLUSIONS: Glenoid inclination can be accurately and reliably measured on MRI.
      Although superior glenoid inclination is statistically greater in those with
      rotator cuff tears than in patients of similar age without rotator cuff tears or
      glenohumeral arthritis, the difference is likely below clinical significance.

PMID- 29576341
TI  - Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell
      infusion.
AB  - OBJECTIVE: To assess if infusion of human bone marrow-derived stem cells (BMDSCs)
      could promote follicle development in patients with impaired ovarian functions.
      DESIGN: Experimental design. SETTING: University research laboratories.
      ANIMAL(S): Immunodeficient NOD/SCID female mice. INTERVENTION(S): Human BMDSCs
      were injected into mice with chemotherapy-induced ovarian damage and into
      immunodeficient mice xenografted with human cortex from poor-responder patients
      (PRs). MAIN OUTCOME MEASURE(S): Follicle development, ovulation, and offspring.
      Apoptosis, proliferation, and vascularization were evaluated in mouse and human
      ovarian stroma. RESULT(S): Fertility rescue and spontaneous pregnancies were
      achieved in mice ovaries mimicking PRs and ovarian insufficiency, induced by
      chemotherapy, after BMDSC infusion. Furthermore, BMDSC treatment resulted in
      production of higher numbers of preovulatory follicles, metaphase II oocytes, 2
      cell embryos, and healthy pups. Stem cells promoted ovarian vascularization and
      cell proliferation, along with reduced apoptosis. In xenografted human ovarian
      tissues from PRs, infusion of BMDSCs and their CD133+ fraction led to their
      engraftment close to follicles, resulting in promotion of follicular growth,
      increases in E2 secretion, and enhanced local vascularization. CONCLUSION(S): Our
      results raised the possibility that promoting ovarian angiogenesis by BMDSC
      infusion could be an alternative approach to improve follicular development in
      women with impaired ovarian function. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT02240342.

PMID- 29576342
TI  - RETRACTED: Letter to the editor "[Toxicology (2017) 159 -159].

PMID- 29576343
TI  - Chemical burn assaults: Is the media coverage representative?

PMID- 29576344
TI  - Genital burns in the United States: Disproportionate prevalence in the pediatric
      population.
AB  - INTRODUCTION AND OBJECTIVES: To describe the epidemiology of genital burns in the
      U.S. and investigate the underlying etiology. METHODS: The National Electronic
      Injury Surveillance System database was queried for individuals who sustained
      genital burns from 2000 to 2016. We collected data on age, gender, injury
      diagnosis, disposition, and causative agents. Multivariate analysis was performed
      to determine predictors of hospitalization. RESULTS: We estimate 17,026 (95% CI
      16,649-17,404) cases of genital burns presented to emergency departments
      nationally. Genital burns occurred more in males than females (12,295 vs 4,731).
      Scalding (57.9%) was the most common mechanism of injury and hot water (35.7%)
      the most common causative agent. Significant predictors of hospitalization on
      multivariate analysis were multi-surface (OR 4.4), scalding (OR 11.5) and thermal
      burns (OR 27.9). Children ages 0-2 had the highest prevalence of genital burns,
      and children ages 0-12 comprised 37.1% of the study. For children <5years of age,
      majority of the burns were caused by hot water in the bathroom. In age group 6
      12, the most common causes of genital burns were cooking-related scalds due to
      hot foods and water. CONCLUSIONS: Children sustain genital burns at a higher rate
      than adults and many appear to have a preventable mechanism. Improved product
      design for safety and educating caregivers about potential hazardous situations
      are needed.

PMID- 29576345
TI  - A review of the validity of malnutrition screening tools used in older adults in
      community and healthcare settings - A MaNuEL study.
AB  - BACKGROUND: Older adults are at increased risk of malnutrition compared to their
      younger counterparts. Malnutrition screening should be conducted using a valid
      malnutrition screening tool. An aim of the Healthy Diet for a Healthy Life (HDHL)
      Joint Programming Initiative (JPI) 'Malnutrition in the Elderly Knowledge Hub'
      (MaNuEL) was to review the reported validity of existing malnutrition screening
      tools used in older adults. METHODS: A literature search was conducted to
      identify validation studies of malnutrition screening tools in older populations
      in community, rehabilitation, residential care and hospital settings. A database
      of screening tools was created containing information on how each tool was
      validated. RESULTS: Seventy-four articles containing 119 validation studies of 34
      malnutrition screening tools used in older adults were identified across the
      settings. Twenty-three of these tools were designed for older adults. Sensitivity
      and specificity ranged from 6 to 100% and 12-100% respectively. Seventeen
      different reference standards were used in criterion validation studies.
      Acceptable reference standards were used in 68 studies; 38 compared the tool
      against the Mini Nutritional Assessment-Full Form (MNA-FF), 16 used clinical
      assessment by a nutrition-trained professional and 14 used the Subjective Global
      Assessment (SGA). Twenty-five studies used inappropriate reference standards.
      Predictive validity was measured in 14 studies and was weak across all settings.
      CONCLUSIONS: Validation results differed significantly between tools, and also
      between studies using the same tool in different settings. Many studies have not
      been appropriately conducted, leaving the true validity of some tools unclear.
      Certain tools appear to be more valid for use in specific settings.

PMID- 29576346
TI  - Patients' experiences with home parenteral nutrition: A grounded theory study.
AB  - BACKGROUND & AIMS: Parenteral nutrition (PN) provides nourishment and hydration
      as an intravenous infusion to patients with intestinal failure (IF). The aim of
      the study is to generate theory that explains the experiences of adult patients
      living with home parenteral nutrition (HPN) and complex medication regimens.
      METHODS: A grounded theory methodology was used to explore the experiences of
      twelve patients receiving HPN. A semi-structured interview was conducted and
      recorded in each participant's home setting. Each interview was transcribed
      verbatim. The simultaneous process of data collection and analysis was followed
      reflecting the principles of the constant comparative approach. RESULTS: A total
      of 15 patients gave written consent, with 12 of them agreeing to be interviewed.
      All the participants had previously undergone surgery as a result of chronic ill
      health or sudden illness. Analysis revealed two core categories: stoma and HPN,
      and these were supported by the subcategories: maintaining stoma output, access
      to toilets, managing dietary changes, maintaining the HPN infusion routine,
      access to technical help to set up an HPN infusion, mobility with HPN equipment
      and general health changes. The strategy of living with loss was demonstrated by
      all the participants, and this was supported by the action strategies of
      maintaining daily activities and social interactions. CONCLUSIONS: This study
      generates new understanding and insight into the views and experiences of
      patients receiving HPN in the UK. The findings from these participants have been
      shown to resonate with the Kubler-Ross Model [1] of the five stages of grief. The
      theory of living with loss was generated by the use of a grounded theory
      methodology. This small scale exploratory study reveals opportunities for
      improvements in practice to be considered by the nutrition support team (NST) and
      other healthcare professionals involved in the patient's hospital stay prior to
      discharge on HPN.

PMID- 29576347
TI  - Intestinal pathogen clearance in children with severe acute malnutrition is
      unrelated to inpatient morbidity.
AB  - BACKGROUND & AIMS: Children with Severe Acute Malnutrition (SAM) often suffer
      from diarrhea, which is associated with increased mortality. The contribution of
      intestinal bacteria, parasites and viruses to morbidity such as diarrhea in SAM
      remains poorly understood. To evaluate their association with clinical outcomes,
      we detected stool pathogens in children with SAM at hospital admission and after
      clinical stabilization prior to discharge. METHODS: 15 intestinal pathogens,
      fecal calprotectin and C-reactive protein (CRP) were determined at admission and
      after clinical stabilization in children aged 8-59 months (n = 47) hospitalized
      in Malawi for complicated SAM. Differences in fecal pathogens, intestinal and
      systemic inflammation, and clinical outcomes between time points were evaluated
      using the Wilcoxon Signed-Rank test or Wilcoxon rank-sum test. RESULTS: On
      admission pathogens were present in nearly all children and after clinical
      stabilization many were cleared with only 55% of children still harboring a
      pathogen (89% vs. 55%, p = 0.001). Nosocomial infections were infrequent. The
      pathogens Giardia lamblia and Shigella spp. were most likely to persist. After
      clinical stabilization, fecal calprotectin was higher in children harboring a
      pathogen (median (IQR): 383 mg/kg (903-149 mg/kg) vs 140 mg/kg (300-71 mg/kg), p
      = 0.03). CRP did not correlate with fecal calprotectin levels nor was it
      associated with pathogen detection. Presence of stool pathogens was not
      associated with clinical outcomes such as diarrhea. CONCLUSIONS: Fecal pathogens
      were very common and cleared in most children with complicated SAM treated with
      antibiotics. The presence of stool pathogens after stabilization was associated
      with increased intestinal inflammation but not with clinical outcomes.
      (http://www.isrctn.com/ISRCTN13916953).

PMID- 29576348
TI  - Value of sarcopenia assessed by computed tomography for the prediction of
      postoperative morbidity following oncological colorectal resection: A comparison
      with the malnutrition screening tool.
AB  - BACKGROUND: Computed tomography (CT) can be used for accurate estimation of whole
      body muscle mass and muscle density and for detection of sarcopenia. The goal of
      this study was to evaluate the additional value of CT measured sarcopenia and
      muscle attenuation alongside the Malnutrition Universal Screening Tool (MUST) for
      the prediction of post-operative morbidity after oncological colorectal
      resection, whilst correcting for known risk factors. METHODS: A prospective
      cohort study of 80 patients undergoing elective colorectal surgery in the
      Netherlands. Patients were screened for nutritional risk upon admission using the
      MUST. Additionally, preoperative CT scans were used to determine skeletal muscle
      mass for the detection of sarcopenia and muscle attenuation. Univariate and
      multivariable analyses were performed to evaluate associations between the MUST,
      muscle attenuation and sarcopenia on the one hand and post-operative
      complications measured by the Clavien-Dindo score on the other hand. RESULTS:
      American Society of Anesthesiology-classification (ASA) >=3, age >=70, MUST >=2
      and lower than median muscle attenuation were significantly associated with a
      higher risk for postoperative complications (Clavien-Dindo score >=2) (p <=
      0.05), whereas sarcopenia was not (p = 0.59). Multivariate analyses showed that
      only MUST >=2 remained significantly associated with postoperative complications
      when corrected for age (p = 0.03, OR 5.8, 95%CI 1.1-29.6), but not when corrected
      for age >=70 and ASA >=3. Muscle attenuation and sarcopenia were not
      significantly associated with postoperative complications. CONCLUSION: Our
      results suggest that using CT measured sarcopenia may have only little additional
      value over the MUST for the prediction of increased short-term post-operative
      morbidity after oncological colorectal surgery. It also underlines the importance
      of currently implemented easy-to-use nutritional screening tools (MUST) and
      raises the question of the evaluation of muscle quality versus quantity in body
      composition imaging. However, further research is needed to investigate the role
      of sarcopenia for predicting outcome after colorectal surgery, and investigate
      the role of muscle attenuation measurements for the prediction of muscle
      function. CATEGORY OF SUBMISSION: observational study.

PMID- 29576349
TI  - Use of both quantitative and qualitative methods to improve assessment of resting
      energy expenditure equation performance in hospitalized adults.
AB  - OBJECTIVE: To introduce the use of qualitative assessment in energy expenditure
      (EE) equation research to improve the understanding of performance of the
      equations in the clinical setting. PATIENTS AND METHODS: Hospitalized individuals
      who had an indirect calorimetry (IC) measurement during their hospital stay from
      2010 to 2012 were included in the study (n = 59). An additional 1000 patients
      hospitalized during this time were used to limit the IC cohort to a more
      "clinically relevant" BMI range (n = 46). The following estimation equations were
      assessed: Harris-Benedict, 25 kcal/kg using actual body weight, Mifflin St. Jeor,
      Ireton-Jones, Penn State, and Owen. Bland-Altman plots with Loess curves were
      generated to compare estimated basal caloric needs between EE equations and IC
      values. RESULTS: This study found a large amount of variability with all EE
      equations. As the mean calorie level increased, the Harris Benedict, Mifflin St.
      Jeor, Penn State, and Owen equations all tended to increasingly under-predict
      caloric need. CONCLUSION: In a research setting a qualitative assessment of EE
      equations can provide a more comprehensive understanding of equation performance
      by complementing traditional quantitative methods. The addition of a Loess curve
      to the Bland-Altman plot further enhances qualitative assessment.

PMID- 29576350
TI  - Differential effects of leucine and leucine-enriched whey protein on skeletal
      muscle protein synthesis in aged mice.
AB  - BACKGROUND & AIMS: It has been suggested that anabolic resistance, or a blunted
      protein synthetic response to anabolic stimuli, contributes to the failure of
      muscle mass maintenance in older adults. The amino acid leucine is one of the
      most prominent food-related anabolic stimuli. However, data on muscle protein
      synthesis (MPS) after administration of a single bolus of leucine in aged
      populations is lacking and long-term single leucine supplementation has not been
      shown to increase muscle mass. This study aimed to determine the MPS response to
      the administration of a single bolus of leucine or to leucine combined with whey
      protein, in aged mice. METHODS: Overnight fasted C57/BL6RJ mice at 25-mo of age
      received an oral gavage with leucine or whey-protein enriched with leucine (0.75
      g/kg bodyweight total leucine in both) or 0.5 mL water (fasted control).
      Subsequently, mice were s.c. injected with puromycin (0.04 MUmol/g bw at t = 30,
      45 or 60 min) and were sacrificed 30 min thereafter. Amino acid concentrations
      were determined in plasma and right muscle tibialis anterior (TA). Left TA was
      used to analyse MPS by SUnSET method and phosphorylation rate of Akt, 4E-BP1 and
      p70S6k by western blot. RESULTS: In aged mice, leucine administration failed to
      increase MPS, despite a 6-fold increase in plasma leucine and elevated muscle
      free leucine levels (P < 0.05). In contrast, leucine-enriched whey protein
      significantly stimulated MPS in aged mice at 60 min after gavage (P < 0.05).
      Muscle free EAA, NEAA and the phosphorylation rate of Akt, 4E-BP1 and p70S6k
      increased significantly (P < 0.05), only after administration of leucine-enriched
      whey protein. CONCLUSIONS: MPS is stimulated in aged mice by leucine-enriched
      whey protein but not by leucine administration only. Administration of other
      amino acids may be required for leucine administration to stimulate muscle
      protein synthesis in aged mice.

PMID- 29576351
TI  - Transthyretin levels: Potential biomarker for monitoring nutritional support
      efficacy and clinical complications risk in patients receiving parenteral
      nutrition.
AB  - : Nutritional support is an effective strategy to restore or maintain nutritional
      status, to reduce clinical complications, hospitalization period and the
      morbidity/mortality risk of hospitalized patients. So, a good marker is important
      to evaluate the nutritional support. OBJECTIVES: This study aims to evaluate the
      evolution of transthyretin levels in patients receiving parenteral nutrition (PN)
      during 14 days. DESIGN & METHODS: Longitudinal study of 88 hospitalized patients.
      The assessments and samples were taken during the first 72 h (T0), on the 7th day
      (T7) and 14th day (T14) of PN. This study was approved by the Ethics Committee of
      the School of Medical Sciences at UNICAMP (No 538/2011). RESULTS: The C-reactive
      protein (CRP) levels were high and albumin and transthyretin levels were low at
      baseline. From T0 to T14, only transthyretin increased (p = 0.03). According to
      the receiver operation characteristic (ROC) curve, we found that the
      transthyretin had some improvement when the CRP levels were less than 10.4 mg/dl
      (T7). According to the CRP/albumin ratio, all patients classified as without risk
      for complications were discharged from the hospital. In addition, we observed
      that patients with transthyretin reduction had a concomitant higher risk for
      complications according to their ratio CRP/albumin (p = 0.03). CONCLUSIONS:
      CRP/albumin ratio was associated with the evolution of transthyretin levels.
      Transthyretin values showed significant improvement in the 14 days of PN.
      Especially, less inflamed patients (ie CRP less than 10.4 mg/dl) improved their
      transthyretin levels. So, CRP value at day 7 that predicts the transthyretin and
      transthyretin is a good biomarker for classification of nutritional support and
      clinical complications risk in patients receiving PN.

PMID- 29576352
TI  - Impact of intermittent fasting on the lipid profile: Assessment associated with
      diet and weight loss.
AB  - Intermittent fasting, whose proposed benefits include the improvement of lipid
      profile and the body weight loss, has gained considerable scientific and popular
      repercussion. This review aimed to consolidate studies that analyzed the lipid
      profile in humans before and after intermittent fasting period through a detailed
      review; and to propose the physiological mechanism, considering the diet and the
      body weight loss. Normocaloric and hypocaloric intermittent fasting may be a
      dietary method to aid in the improvement of the lipid profile in healthy, obese
      and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides
      and increasing HDL levels. However, the majority of studies that analyze the
      intermittent fasting impacts on the lipid profile and body weight loss are
      observational based on Ramadan fasting, which lacks large sample and detailed
      information about diet. Randomized clinical trials with a larger sample size are
      needed to evaluate the IF effects mainly in patients with dyslipidemia.

PMID- 29576353
TI  - Improving nutrition care and intake for older hospital patients through system
      level dietary and mealtime interventions.
AB  - BACKGROUND & AIMS: Interventions such as oral nutritional supplements (ONS),
      fortified meals and mid-meals, feeding assistants and Protected Mealtimes have
      shown some impact on nutritional intake in research studies, but embedding them
      in practise remains challenging. This study monitored nutritional intake of older
      medical inpatients as dietary and mealtime interventions were progressively
      implemented into routine practise. METHODS: Series of three prospectively
      evaluated patient cohorts allowed comparison of nutritional intake of 320
      consented medical inpatients aged 65 + years: cohort 1 (2007-8), cohort 2 (2009)
      and cohort 3 (2013-14) as nutrition care interventions were progressively
      introduced and embedded. Interventions focused on 'assisted mealtimes', fortified
      meals and mid-meals, and ONS. Energy and protein intake were calculated from
      visual plate waste of individual meal and mid-meal components on day 5 of
      admission. Nutrition care processes were evaluated by mealtime audits of diet
      type, assistance and interruptions on the same day. One-way ANOVA and chi square
      tests were used for comparison between cohorts. RESULTS: Significant, progressive
      improvements in energy and protein intake were seen between cohorts (energy:
      cohort 1: 5073 kJ/d; cohort 2: 5403 kJ/d; cohort 3: 5989 kJ/d, p = 0.04; protein:
      cohort 1: 48 g/d, cohort 2: 50 g/d, cohort 3: 57 g/d, p = 0.02). Greater use of
      fortified meals and mid-meals and sustained improvements in mealtime assistance
      likely contributed to these improvements. CONCLUSIONS: Multi-faceted system-level
      approach to nutrition care, including changes to dietary and mealtime care
      processes, was associated with measureable and sustained improvements in
      nutritional intake of older inpatients over a seven year period.

PMID- 29576354
TI  - Aged garlic extract supplementation modifies inflammation and immunity of adults
      with obesity: A randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Obesity is a serious global health issue and often results in low
      grade systemic inflammation, increasing the risk for several chronic diseases. If
      obesity-induced inflammation could be reduced, fewer complications and co
      morbidities might occur. OBJECTIVE: To investigate whether daily supplementation
      with aged garlic extract (AGE) could reduce chronic inflammation and improve
      immune function in adults with obesity. METHODS: Fifty-one healthy adults with
      obesity (mean age 45.6 +/- 1.6 years, mean BMI 36.1 +/- 0.9 kg/m2) were recruited
      to participate in a parallel, double-blind, placebo-controlled, randomized study.
      After being matched by BMI, participants were randomized into the AGE
      supplementation or placebo group. Participants were asked to take a divided daily
      dose of 3.6 g AGE or placebo, with food for 6 weeks. Blood lipid and inflammatory
      markers were assessed at baseline and after 6 weeks of supplementation.
      Additionally, peripheral blood mononuclear cells (PBMC) were isolated from whole
      blood and used to detect changes in immune cell populations and levels of
      cytokine secretion. A one-way ANCOVA was performed to evaluate differences
      between the two groups, controlling for respective baseline values. RESULTS: At
      the end of study, serum IL-6 (p = 0.04) and TNF-alpha (p = 0.05) of participants
      consuming AGE were significantly lower than those consuming the placebo capsules.
      PBMC flow cytometry results showed that participants from the AGE group had a
      higher proportion of gammadelta-T cells (p = 0.03) and a lower proportion of NKT
      cells (p = 0.02) in the total population of lymphocytes. There was no difference
      in percentage of NK cells between the two groups. A significant difference in
      blood LDL concentration was also observed (p = 0.05). Total cholesterol and non
      HDL cholesterol tended to differ between participants from the AGE group and
      those from the placebo group, although values did not achieve statistical
      significance. CONCLUSION: Six weeks of AGE consumption modulated immune cell
      distribution, prevented the increase of serum TNF-alpha and IL-6 concentrations
      and reduced blood LDL concentration in adults with obesity. AGE, taken
      consistently, may be beneficial in preventing the development of chronic diseases
      associated with low-grade inflammation in adults with obesity. Registered under
      ClinicalTrials.gov with the identifier code NCT01959646.

PMID- 29576355
TI  - Nutrition therapy for critically ill patients across the Asia-Pacific and Middle
      East regions: A consensus statement.
AB  - BACKGROUND & AIMS: Guidance on managing the nutritional requirements of
      critically ill patients in the intensive care unit (ICU) has been issued by
      several international bodies. While these guidelines are consulted in ICUs across
      the Asia-Pacific and Middle East regions, there is little guidance available that
      is tailored to the unique healthcare environments and demographics across these
      regions. Furthermore, the lack of consistent data from randomized controlled
      clinical trials, reliance on expert consensus, and differing recommendations in
      international guidelines necessitate further expert guidance on regional best
      practice when providing nutrition therapy for critically ill patients in ICUs in
      Asia-Pacific and the Middle East. METHODS: The Asia-Pacific and Middle East
      Working Group on Nutrition in the ICU has identified major areas of uncertainty
      in clinical practice for healthcare professionals providing nutrition therapy in
      Asia-Pacific and the Middle East and developed a series of consensus statements
      to guide nutrition therapy in the ICU in these regions. RESULTS: Accordingly,
      consensus statements have been provided on nutrition risk assessment and
      parenteral and enteral feeding strategies in the ICU, monitoring adequacy of, and
      tolerance to, nutrition in the ICU and institutional processes for nutrition
      therapy in the ICU. Furthermore, the Working Group has noted areas requiring
      additional research, including the most appropriate use of hypocaloric feeding in
      the ICU. CONCLUSIONS: The objective of the Working Group in formulating these
      statements is to guide healthcare professionals in practicing appropriate
      clinical nutrition in the ICU, with a focus on improving quality of care, which
      will translate into improved patient outcomes.

PMID- 29576356
TI  - Thickness of the adductor pollicis muscle: Accuracy in predicting malnutrition
      and length of intensive care unit stay in critically ill surgical patients:
      Thickness of the adductor pollicis muscle in surgical critically patients.
AB  - BACKGROUNDS & AIMS: new techniques for assessment of nutritional status of
      critically ill and surgical patients have been investigated to overcome inherent
      limitations of conventional method. The current study aimed to evaluate the
      ability of thickness of the adductor pollicis muscle (TAPM) in detecting
      malnutrition and predicting morbidity and mortality in critically ill surgical
      patients. METHODS: cohort study of adult patients, assessed within the 48 h of
      admission to the surgical intensive care unit (ICU) of a public hospital. TAPM
      measurements of the non-dominant hand were performed with patients lying supine.
      TAPM values lower than the 5th percentile for age and sex were adopted to
      identify malnutrition. Patients were followed up until discharge for measurement
      of the following parameters: length of ICU stay, time on mechanical ventilation,
      length of hospital stay, and hospital mortality. RESULTS: fifty-nine surgical ICU
      patients, with mean age of 60.0 +/- 17.4 years were included in the current
      study. There was a positive, weak-to-moderate correlation between TAPM and
      anthropometric indicators (r = 0.338 to r = 0.579; p < 0.01). The ability of TAPM
      in identifying patients with malnutrition (diagnosed by global subjective
      assessment) was assessed by ROC curve analysis, and an area under the ROC curve
      of 0.611 (95%CI: 0.459-0.762; p = 0.151) was found. TAPM < p5 increased the risk
      of ICU length of stay >3 days (RR = 2.92; 95%CI 1.09-7.81; p = 0.032). Relative
      frequencies of malnourished and well-nourished patients according to TAPM were
      not different between survivors and non-survivors (p = 0.814). CONCLUSION: TAPM
      showed unsatisfactory accuracy in predicting malnutrition. Although TAPM was not
      a good mortality predictor, reduced TAPM (< p5) values increased the risk of a
      prolonged ICU stay (>3 days).

PMID- 29576357
TI  - Longitudinal changes in phase angle by bioimpedance in intensive care patients
      differ between survivors and non-survivors.
AB  - BACKGROUND & AIMS: Intensive care (ICU) patients suffer from metabolic stress,
      creating a catabolic state which might disturb nutritional status and body
      composition. Alterations in body fluid compartments by disease or massive volume
      resuscitation could invalidate bioimpedance hydrometry. Still bioimpedance might
      give other information. METHODS: 52 ICU patients (35 male, 17 female, mean age 66
      years), BMI 29,2 were assessed by bioimpedance spectroscopy. Phase angle (PhA) at
      50 kHz was assessed. RESULTS: On first assessment PhA was 3.7 +/- 1.0 degrees .
      In 26 patients reassessed after median 5 days PhA was not significantly changed,
      although R 50 kHz and Xc 50 kHz both increased (p = 0.047), indicating
      diminishing overhydration. Body weight and body cell mass decreased by 1.8 +/-
      5.7 and 2.8 +/- 7.5 kg (p = 0.13). Fat free mass and extracellular water
      decreased 4.5 +/- 8.9 kg (p = 0.032) and 1.5 +/- 3.5 kg (p = 0.031), while CRP
      decreased 63 mg/l (p = 0.002). In 17 survivors PhA increased 0.62 +/- 1.24
      degrees  (NS), while in 9 non-survivors PhA decreased 0.24 +/- 0.82 degrees  (p =
      0.06), with 0.86 degrees  difference (p = 0.049) between groups. CONCLUSION:
      Phase angle by bioimpedance is very low in ICU patients and positive changes in
      PhA seems to reflect more favorable outcome. Bioimpedance by Body Scout appears
      unsuitable for the assessment of fat free mass or overhydration in ICU patients.

PMID- 29576358
TI  - A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces
      symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo
      controlled, double-blind clinical trial.
AB  - BACKGROUND & AIMS: Many women experience emotional and physical symptoms around
      the time of ovulation and more so before menstruation interfering with their
      daily normal life also known as premenstrual syndrome (PMS). Recent observational
      data suggest that supplementation with Lipogen's phosphatidylserine (PS) and
      phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of
      this study was to confirm these observations on the effects of PAS on PMS symptom
      severity within a controlled clinical trial setting. METHODS: Forty women aged 18
      45 years with a diagnosis of PMS were assigned to either take PAS (containing 400
      mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site
      visits including 1 baseline menstrual cycle followed by 3 treatment cycles.
      Treatment intake was controlled for by using an electronic device, the Medication
      Event Monitoring System (MEMS(r)). Primary outcome of the study was the PMS
      symptoms severity as assessed by using the Daily Record of Severity of Problems
      (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual
      Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening
      response (CAR) and evening cortisol levels) as well as serum levels (cortisol,
      estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed.
      RESULTS: PMS symptoms as assessed by the DRSP Total score showed a significantly
      better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo.
      In addition, PAS treated women reported a greater improvement in physical (p =
      0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction
      of productivity (p = 0.052) and a stronger decrease in interference with
      relationships with others (p = 0.099) compared to the placebo group. No other
      DRSP scale or item showed significant results. Likewise, the reduction in the
      number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD)
      criteria as classified by the SIPS did not differ between the PAS and the placebo
      group. For the biomarkers, the salivary cortisol percentage increase of the CAR
      was significantly less pronounced in the follicular phase of cycle 4 than in the
      follicular phase of cycle 1 for subjects taking PAS when compared to subjects
      taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels
      between visit 1 and visit 5 differed significantly between groups (p = 0.043).
      While serum cortisol levels of PAS treated females slightly decreased between
      visit 1 and visit 5, cortisol levels of females treated with placebo increased.
      For all other biomarkers, no treatment effects were observed over the 4 cycles
      study period. Overall, this study confirms that a daily intake of PAS, containing
      400 mg PS and 400 mg PA, can be considered as safe. CONCLUSIONS: Results
      substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the
      recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the
      Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive
      results of this clinical study merits consideration of developing the PAS complex
      as a botanical drug for treatment of PMDD. CLINICAL TRIAL REGISTRATION: The study
      is registered at Deutsches Register Klinischer Studien with the registration
      number DRKS00009005.

PMID- 29576359
TI  - Correlation of symptoms to serum vitamin D levels?
AB  - BACKGROUND AND OBJECTIVE: Recent studies have shown that vitamin D plays an
      important role in many disease processes. However, data is lacking which
      correlates the common symptoms attributed with vitamin D levels. This study was
      undertaken to find the correlation of symptoms and Vitamin D levels among ethnic
      Saudi Arabian population. METHODS: A structured questionnaire was made and
      translated in the Arabic language, which included, age, weight and height,
      ethnicity and marital status. Patients who were visiting orthopaedic clinics for
      the first time were included after a detailed history, which ruled out any
      associated metabolic conditions. Patient's biometric data and the answering of
      the questionnaire were conducted by one of the senior members of the research
      group. The symptoms which were included in the questionnaire were fatigue, muscle
      cramps, joint and back pain, blood sugar levels, recurrent infections, hair loss,
      mood swings, weight gain, irritable bowel, fractures and history of malignancy.
      All the scores were graded between 1 and 9 (mildest 1 and severe 9) and only for
      fracture and malignancy it was yes/no answer. A score of <=4 was accepted as no
      impact of the vitamin D levels on symptoms and answer of >=5 was accepted as
      impact on the symptoms. Residents whose mother tongue was Arabic conducted all
      interviews. Blood was collected for 25 OHD levels, calcium and parathyroid
      hormone levels. Deficiency of vitamin D was defined as <=20 ng/ml, insufficiency
      21-29 ng/ml and normal level >=30 ng/ml. The data was entered in the data base
      and analyzed using SPSS Inc Version 20. RESULTS: Two hundred one patients
      completed the questionnaire but for final analysis the data of 187 was available
      for analysis as in 14 patients some of the data was missing. All were females and
      the average age was 55.9 +/- 12.4 years, weight 78.9 +/- 14.2 kg and height was
      1.56 +/- 7.01 m. The mean calcium level was 9.12 +/- 0.33 mg/dl and, parathyroid
      hormone was 8.1 +/- 6.06 pc/ml. The average 25 hydroxy vitamin D3 (25OHD) level
      was 21.8 +/- 10.22 ng/ml. Forty-four (23.5%) of women had a normal vitamin D
      level, 51 (27.27%) had insufficiency and 92 (49.19%) had deficiency. Patients who
      complained of muscle cramps had 25OHD level of 18.86 +/- 8.73 compared to
      patients who had no complains of cramps, 23.45 +/- 9.2 ng/ml (p < 0.001) and
      symptom severity score (SSC) p value of p < 0.000. The results were similar for
      fatigue, Back pain, hair loss, mood swings and weight gain of P < 0.04, p < 0.07,
      p < 0.05, <0.03 and p < 0.09 for vitamin D levels and p < 0.001 for SSS. Forty
      eight (25.6%) had a previous fracture in their history. CONCLUSIONS: This study
      shows that many symptoms, which have been attributed to low vitamin D levels, are
      not true. Muscle Cramps, fatigue, mood swings, hair loss, back pain and weight
      gains appears to be more common in patients with low 25OHD levels.

PMID- 29576360
TI  - The impact of Home Parenteral Nutrition on the lives of adults with Type 3
      Intestinal Failure.
AB  - BACKGROUND & AIMS: Several studies have been published reporting on the impact of
      Home Parenteral Nutrition (HPN) on the lives of people with Type 3 Intestinal
      Failure. These studies focused on symptoms and functional limitations resulting
      from the treatment. The aim of this study was to determine how dependence on HPN
      affects individuals' ability to fulfil their human needs. METHODS: Unstructured
      qualitative interviews were conducted with people dependent on HPN, who were
      asked to explain how their lives were affected by the treatment. Theoretical
      thematic analysis was conducted on the interview transcripts to identify
      statements describing aspects of human needs that were left unfulfilled. Care was
      taken to separate the impact of HPN from that of the underlying disease. RESULTS:
      Interviews were conducted with 30 patients (53% female; mean age, 55.9 (range 35
      76) years). Most of the sample (87%) had short bowel syndrome. Major aspects of
      need affected by HPN were related to: autonomy, cognition, relationships, role
      fulfilment, socialisation, appearance and self-esteem, appetite and perceived
      vulnerability. CONCLUSIONS: The study illustrates how patients' lives are
      affected by HPN. Statements generated from this qualitative study were used to
      produce the Parenteral Nutrition Impact Questionnaire (PNIQ), a patient-centric
      measure of quality of life specific to people using HPN.

PMID- 29576361
TI  - Can energy intake alter clinical and hospital outcomes in PICU?
AB  - BACKGROUND & AIMS: Energy is essential for the treatment and recovery of children
      admitted to Pediatric Intensive Care Units (PICU). There are significant
      immediate and long-term health consequences of both under- and over-feeding in
      this population. Energy requirements of critically ill children vary depending on
      age, nutritional status, sepsis, fever, pharmacotherapy, and duration and stage
      of critical illness. This study aimed to determine the incidence of over- and
      under-feeding and to compare hospital outcomes between these feeding categories.
      Secondary outcomes were collected to describe the association between feeding
      categories and biochemistries (serum lactate, triglycerides, C-reactive protein).
      METHODS: An ethics approved retrospective study of children admitted to PICU was
      performed. All intubated patients admitted to PICU (2008-2013) were included,
      except those in which an IC test was not feasible. Data collection included
      demographics, the primary outcome variable reported as under feeding (<90%MREE),
      appropriate (MREE +/-10%) or overfeeding (>110% MREE) determined through
      comparison of measured resting energy expenditure (MREE) using indirect
      calorimetry (IC) to actual energy intake based on predicted basal metabolic rate
      (PBMR) and clinical outcomes mechanical ventilation and PICU length of stay
      (LOS). Data were analysed with descriptive methods, ANOVA and linear regression
      models. RESULTS: A total of 139 patients aged 10 (range 0.03-204) months were
      included. Sixty (43%) were female and 77 (55%) were admitted after a surgical
      procedure. A total of 210 IC tests were conducted showing a statistically
      significant difference between MREE measurements and PBMR (p = 0.019). Of the 210
      measurements, only 26 measures (12.4%) demonstrated appropriate feeding, while 72
      (34.3) were underfed and 112 (53.3%) were overfed. Children who were overfed had
      significantly longer PICU LOS (median 45.5, IQR 47.8 days) compared to those
      children in the appropriately fed (median 21.0, IQR 54.5 days), and underfed
      groups (median 16.5, IQR 21.3 days). There was a mean difference between the over
      and under feeding category and ventilation days after adjusting for age and PRISM
      score (p = 0.026), suggesting decreased mechanical ventilation days for underfed.
      Children who were underfed had significantly higher CRP (median 75.5, IQR 152.8
      mg/L) compared to those children in the appropriately fed (median 57.8, IQR 90.9
      mg/L) and overfed groups (median 22.4, IQR 56.2 mg/L). CONCLUSIONS: This
      retrospective study confirms that estimations of energy expenditure in critically
      ill children are inaccurate leading to unintended under and overfeeding.
      Importantly under feeding seems to be associated with fewer mechanical
      ventilation days and PICU LOS. Further research is required to elucidate the role
      of optimal nutrition in altering clinical variables in this population.

PMID- 29576362
TI  - The impact of body mass index on post resuscitation survival after cardiac
      arrest: A meta-analysis.
AB  - BACKGROUND: Observational studies examining the association between body mass
      index (BMI) and the outcome of cardiac arrest (CA) shows controversial results.
      METHODS: We reviewed literature for studies assessing the impact of BMI on
      survival and neurological outcome following CA. Eligible studies were
      subsequently meta-analyzed and pooled odds ratios and their corresponding 95%
      confidence intervals for post CA survival and neurological status were derived.
      RESULTS: A total of 7 studies with 24,651 patients were evaluable for this meta
      analysis. The studies were also categorized by location of the CA and the use of
      therapeutic hypothermia. Our results suggested that BMI between 25 and 29.9
      kgr/m2 had a favorable impact on survival after CA (OR = 1.172, 95% CI, 1.109
      1.236) in comparison to normal weight subjects. Likewise, overweight patients
      presented increased odds for a favorable neurological outcome after CA (OR =
      1.112, 95% CI, 1.020-1.213). On the contrary, underweight subjects presented
      decreased odds of surviving after CA as compared to normal BMI subjects (OR =
      0.781, 95% CI, 0.652-0.935). Finally, BMI >30 kgr/m2 was not associated with
      improved survival or neurological outcome as compared to BMI 18.5-24.9 kgr/m2.
      CONCLUSIONS: Overweight patients have a favorable prognosis after CA in terms of
      both survival and neurological outcome. This effect was amplified when the
      analysis is restricted in in-hospital cardiac arrest and in patients non-treated
      with therapeutic hypothermia.

PMID- 29576363
TI  - Hyperlipidemia secondary to acitretin therapy for lamellar ichthyosis associated
      with a NIPAL4 mutation improves on a plant-based diet and relapses on a standard
      Western diet.
AB  - Oral retinoids are commonly prescribed for many dermatological conditions and may
      induce hyperlipidemia. We document the case of a 35-year-old man taking acitretin
      for congenital lamellar ichthyosis associated with a homozygous deleterious
      mutation in NIPAL4 who developed retinoid-induced hyperlipidemia that responded
      dramatically to a whole-food plant-based (WFPB) diet. On presentation, his diet
      consisted of chicken, fish, low fat meats and dairy, grains, and some fruits and
      vegetables. He then adopted a WFPB diet without making changes to his
      medications. His serum lipid levels dropped and his exercise capacity improved.
      Five months later, after discontinuing the plant-based diet and returning to his
      baseline diet, his hyperlipidemia returned and persisted despite adjustments to
      his medications. After a year and a half, the patient again adopted a plant-based
      diet and his lipid levels fell sharply again. A WFPB diet helped improve and
      control serum lipid levels in a patient with retinoid-induced hyperlipidemia.
      Future interventions should focus on ways to help patients successfully adopt and
      maintain a WFPB diet, as increased adherence to a healthy lifestyle is associated
      with greater health benefits.

PMID- 29576364
TI  - Anthropometric and demographic predictors of handgrip strength and lean mass
      quality in hospitalized individuals.
AB  - BACKGROUND AND AIM: Low strength and/or lean mass quality are associated with
      higher hospitalization and mortality. The aim of this study was to evaluate the
      main demographic and anthropometric predictors of strength and lean mass quality
      in hospitalized patients. METHODS: We evaluated 136 patients (18-86 years) of
      both sexes, admitted in a public hospital. Waist circumference (WC) was measured
      using an inelastic tape, lean mass (LM) was assessed by bioimpedance, and
      handgrip strength (HGS) was performed using a dynamometer. Lean mass quality
      (HGS/LM) was also calculated. RESULTS: We noted that LM predicted 33.1% of HGS,
      whereas WC was not associated with HGS. Evaluating LM and WC in the same
      statistical model, WC (beta = -0.249, p = 0.001) increased the prediction of HGS
      by 4.7% when compared to LM alone. Accessing LM, WC, age, and sex in the same
      model an increase in the prediction of HGS by 7.3% was noted when compared to LM
      alone, but only LM and sex were significant. In addition, WC predicted the lean
      mass quality by 4% (beta = -0.205, p = 0.016) and when WC, sex, and age were
      placed in the same model; WC (beta = -0.172, p = 0.035) and sex (beta = 0.332, p
      < 0.001) explained the variations in lean mass quality by 15%. CONCLUSION: The
      main predictor of lower HGS was lower LM, whereas sex showed a low association.
      Furthermore, although a low association was found, higher abdominal obesity and
      sex predicted lower lean mass quality.

PMID- 29576365
TI  - Comparison of predictive equations of lean mass in young and postmenopausal
      women.
AB  - BACKGROUND AND AIM: The lean mass (LM) is a predictor of functional capacity,
      quality of life, and mortality. In this way, the LM should be measured by
      reliable methods. However, it presents high cost and generally predictive
      equations are used in clinical practice, but little is known which is the best
      predictive equation of LM in women. The purpose of the present study was to
      verify which predictive equation of LM correctly estimates the LM in young and
      postmenopausal women. METHODS: Eighty-one women aged 19-81 years were evaluated.
      Body weight, height, waist circumference, and skin folds (bicipital, tricipital,
      subscapular and suprailiac) were measured. The LM was evaluated by DXA and also
      estimated using the predictive equations of Hume I, Hume II, Salamat, Kulkarni I,
      and Kulkarni II. Bland-Altman analysis was performed to evaluate the
      over/underestimation of the LM by predictive equations. RESULTS: The equations of
      Salamat, Kulkarni II, Hume I and Kulkarni I overestimated the LM by 0.0 (7.0; 
      6.9) kg; 2.3 (7.5; -3.0) kg; 5.1 (9.0; 0.4) kg; and 9.7 (16.3, 3.1) kg,
      respectively; whereas Hume II equation underestimated the LM by -16.9 (-11.5; 
      22.2) kg. CONCLUSIONS: The equation that presented a better prediction of LM was
      Salamat. However, it should be used with caution in clinical practice since this
      equation showed elevated confidence intervals and limits of agreements, and can
      lead to significant errors for some individuals.

PMID- 29576366
TI  - Low caloric and protein intake is associated with mortality in patients with
      acute kidney injury.
AB  - BACKGROUND: Acute renal injury (AKI) interferes greatly with nutritional status,
      affecting the metabolism of all macronutrients and increased mortality rates in
      hospitalized patients. Our objective was to evaluate the association of
      nutritional parameters (albumin, cholesterol, caloric and protein intake and
      nitrogen balance (NB)) with mortality in patients with AKI. METHODS: This is a
      prospective observational study that evaluated 595 consecutive patients over the
      age of 18 years with AKI, requiring enteral or parenteral feeding. At the time of
      the patient's enrollment, demographic and laboratorial data, caloric and protein
      supply and NB were recorded on the first day of referral to the nephrologist. All
      patients were followed throughout the hospital stay and mortality rate was also
      recorded. RESULTS: The medium age of patients with AKI was 64 (54-75) years,
      64.5% male, 62% admitted to intensive care unit (ICU), 52% on dialysis and the
      majority (48%) were at stage 3 by AKIN. Length of stay and hospital mortality
      were 18 (10-31) days and 46%, respectively. Superior age, AKI severity, lower
      body weight and body mass index (BMI), higher need for dialysis, ICU admission
      and shorter hospital stay were associated with higher mortality. At logistic
      regression, caloric (OR: 0.946; CI:95%: 0.901-0.994; p:0.029) and protein intake
      (OR: 0.947; CI:95%: 0.988-0.992; p = 0.028) and serum albumin (OR: 0.545; CI:95%:
      0.401-0741; p < 0.001) were associated with hospital mortality. Cholesterol (OR:
      0.995; CI:95%: 0.991-1.000; p = 0.052) was not associated with increased
      mortality in the adjusted analysis. Analysis of the receiver operating
      characteristic (ROC) curve showed that calorie intake < 12 kcal/kg (AUC: 0.745;
      CI:95%: 0.684-0.765; p < 0.001) and protein intake < 0.5 g/kg (AUC: 0.726;
      CI:95%: 0.686-0.767; p < 0.001) were predictors of hospital mortality, as well as
      a negative NB < -6.47 g N/day (AUC: 0.745; CI:95%: 0.704-0.786; p < 0.001).
      CONCLUSIONS: In conclusion, low caloric and protein intake, negative NB and low
      albumin value are conditions associated with higher hospital mortality in
      patients with AKI.

PMID- 29576367
TI  - Association of dietary and serum magnesium with glucose metabolism markers: The
      Furukawa Nutrition and Health Study.
AB  - BACKGROUND & AIMS: Magnesium may play an important role in cardio-metabolic
      abnormalities, including type 2 diabetes, but epidemiological evidence linking
      magnesium status to glucose metabolism is limited among Asians. We cross
      sectionally examined the association of dietary and serum magnesium with markers
      of glucose metabolism among Japanese subjects. METHODS: Subjects were 1796
      workers, aged 18-78 years, who participated in a health survey. Dietary magnesium
      intake was assessed with a validated brief diet history questionnaire. Serum
      magnesium concentrations were measured using an enzymatic method. Multivariable
      linear regression models were used to estimate means of fasting insulin, fasting
      plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR),
      homeostatic model assessment of beta-cell function (HOMA-beta), and glycated
      hemoglobin (HbA1c), with adjustments made for potential confounding variables.
      RESULTS: Dietary magnesium was inversely associated with HOMA-IR (Ptrend = 0.01).
      Multivariable-adjusted means (95% confidence intervals) of HOMA-IR for the lowest
      to highest quartiles of dietary magnesium were 0.94 (0.89-0.99), 0.92 (0.88
      0.97), 0.88 (0.83-0.92), and 0.86 (0.81-0.90). Serum magnesium concentrations
      were also inversely associated with HOMA-IR (Ptrend = 0.04) and HbA1c (Ptrend
      <0.01). Multivariable-adjusted means (95% confidence intervals) for the lowest to
      highest quartiles of serum magnesium were 0.94 (0.90-0.98), 0.87 (0.83-0.91),
      0.90 (0.85-0.95), and 0.86 (0.81-0.92) for HOMA-IR and 5.41 (5.36-5.45), 5.33
      (5.28-5.37), 5.30 (5.25-5.36), and 5.28 (5.22-5.35) for HbA1c. Excluding subjects
      with diabetes did not materially change the association between dietary magnesium
      and HOMA-IR (Ptrend <0.01), while it attenuated the association of serum
      magnesium with HOMA-IR (Ptrend = 0.27) and HbA1c (Ptrend = 0.15). CONCLUSIONS:
      The present findings suggest that lower dietary magnesium, but not serum
      magnesium, is associated with IR in apparently healthy adults.

PMID- 29576368
TI  - Reliability of ultrasonographic arm muscle thickness measurement by various
      levels of health care providers in ICU.
AB  - PURPOSE: Reliability of arm muscle thickness measurement using ultrasonography
      (USG) by operators of varied experience is unknown. Hence, we planned this study
      to determine the reliability of arm muscle thickness measured using USG by 5
      observers with variable experience. MATERIALS AND METHOD: This was a cross
      sectional observational study which included critically ill patients with sepsis.
      Arm muscle thickness was measured in triplicate on Siemens ACUSON X300TM USG
      machine by each of 5 observers. Intra-class correlation coefficient (ICC) was
      computed to assess intra-observer and inter-observer variability of multiple
      observations. RESULTS: This study included 45 (30 - male) patients. Mean (+/-SD)
      age, APACHE and SAPS score of the participants were 54.95 (+/-15.97) years, 14.66
      (+/-4.57) and 2.6 (+/-1.37), respectively. There were 135 observations by each
      observer. ICC (95%CI) for intra-observer reliability study for observer 1, 2, 3,
      4, and 5 were 0.997 (0.995-0.998), 0.996 (0.993-0.998), 0.997 (0.996-0.998),
      0.997 (0.994-0.998) and 0.998 (0.986-0.999), respectively. ICC (95%CI) for inter
      observer reliability study for 1st, 2nd and 3rd reading were 0.963 (0.943-0.977),
      0.992 (0.988-0.995) and 0.992 (0.988-0.995), respectively. CONCLUSIONS: There was
      an excellent intra- and inter-observer agreement among 5 observers for
      measurement of arm muscle thickness using bedside USG among patients with sepsis.

PMID- 29576370
TI  - Small intestinal absorption in patients with chronic obstructive pulmonary
      disease complicated by cor pulmonale - A pilot study.
AB  - BACKGROUND: Cor pulmonale is a common complication to Chronic Obstructive
      Pulmonary Disease (COPD), and may result in increased pressure in the inferior
      caval vein and stasis of the liver. The chronic pulmonary hypertension may lead
      to stasis in the veins from the small intestine and thereby compromise absorption
      of nutrients. AIM: To investigate whether patients with pulmonary hypertension
      have reduced absorption capacity compared to COPD patients without cor pulmonale.
      METHODS: Absorption of d-xylose (25 g) and zinc (132 mg), administered as a
      single dose, was tested in 14 COPD patients, seven with and seven without cor
      pulmonale. The presence of cor pulmonale was determined by echocardiography. The
      concentration of d-xylose and zinc were measured in peripheral blood one, two and
      three hours after ingestion and used as markers of absorption. Furthermore, urine
      was collected for five hours to determine the amount of excreted d-xylose.
      RESULTS: No significant difference in absorption of d-xylose (p = 0.28) or zinc
      (p = 0.51) was found between the two groups. However, a trend towards a delay in
      d-xylose absorption, as assessed by time-to-peak concentration, was observed in
      patients with cor pulmonale (p = 0.08). There was no significant difference in
      the amount of excreted d-xylose in the urine between the groups (p = 0.52). No
      correlation was found between the tricuspid regurgitation gradient and the
      absorption of both test-markers (rs = 0.34 and rs = -0.25). Likewise, no
      correlations were found between the inferior caval pressure during the in- and
      expiration phases and the absorption of d-xylose (rs = -0.09 rs = 0.23) or zinc
      (rs = -0.39, rs = -0.39). CONCLUSION: We found no indications that small
      intestinal absorption is affected in a clinically relevant degree in patients
      with cor pulmonale.

PMID- 29576369
TI  - The effect of long-term weight-loss intervention strategies on the dynamics of
      pancreatic-fat and morphology: An MRI RCT study.
AB  - BACKGROUND & AIMS: The ability to mobilize pancreatic-fat and the meaning of
      decreased fat in the pancreas remain controversial. We followed the dynamics of
      pancreatic-fat and its morphology during various long weight-loss induced
      lifestyle-interventions. METHODS: In isolated workplace with monitored/provided
      lunch, we randomly assigned healthy persons with abdominal obesity or
      dyslipidemia for one of two 18-month equal-caloric diets: low-fat (LF) or
      Mediterranean/low-carbohydrate (Med/LC, with provided 1oz walnuts/day), with or
      without added moderate exercise (supervised gym membership). We used magnetic
      resonance-imaging to quantify pancreatic-fat and morphology. RESULTS: At
      baseline, 277 eligible participants (mean age = 48 years; 88% men; pancreatic-fat
      = 17.4 +/- 5.1%) had higher pancreatic-fat in men (17.7 +/- 4.9% vs 14.9 +/- 5.5%
      in women; p = 0.004). Following 18-month intervention (adherence = 86.3%) and
      moderate weight-loss (mean = -3.0 +/- 5.5 kg), pancreatic-fat decreased
      moderately but significantly (-0.26 +/- 2.18% units; p = 0.049). Med/LC diet
      induced a greater decrease in pancreatic-fat compared to LF (p = 0.043), and the
      combination of Med/LC diet + exercise exhibited the highest reduction (-0.69%
      units) as compared to LF diet without exercise (+0.12%units; p = 0.027 between
      groups). In multivariate regression models, after further adjusted for visceral
      adipose-tissue (DeltaVAT), pancreatic-fat loss associated with both decreases in
      pancreatic-morphology ratio (perimeter divided by area; beta = 0.361; p < 0.001)
      and superficial-subcutaneous adipose-tissue loss (beta = 0.242; p = 0.001), but
      not with changes in intrahepatic-fat (beta = -0.034; p = 0.638). Pancreatic-fat
      loss associated with increased intake of polyunsaturated-fat (beta = -0.137; p =
      0.032), as with improved high-density lipoprotein-cholesterol (HDL; beta = 
      0.156; p = 0.023) and triglycerides/HDL ratio (beta = 0.162; p = 0.015),
      independently of DeltaVAT, but not with glycemic-control parameters (e.g. HbA1c,
      HOMA-IR and HOMA-beta; p > 0.2 for all). CONCLUSIONS: Pancreatic-fat loss is
      mainly associated with improved lipid, rather than glycemic profiles. Med/LC
      diet, mostly with exercise, may benefit pancreatic-fat loss. Pancreatic
      morphology could serve as a biomarker of pancreatic-fat state.
      (ClinicalTrials.gov identifier: NCT01530724).

PMID- 29576371
TI  - Evaluation of water balance in a population of older adults. A case control
      study.
AB  - Older adults are at risk for dehydration and its' potentially life-threatening
      consequences. Unrecognized dehydration can complicate chronic medical problems
      and increase morbidity. The objective of the study was to estimate water balance,
      intake and loss in elderly people living in Greece using the Water Balance
      Questionnaire (WBQ). WBQ was administered in winter to 108 independents (65
      81yrs) (Group A), 94 independents (82-92yrs) (Group B) and 51 hospitalized (65
      92yrs) (Group C). A database from previous study of 335 adults (18-65yrs)
      (Control Group) used for comparison. Mean estimates of water balance, intake and
      loss were, respectively, for Group A -749 +/- 1386 mL/day, 2571 +/- 739 mL/day
      and 3320 +/- 1216 mL/day, for Group B -38 +/- 933 mL/day, 2571 +/- 739 mL/day and
      3320 +/- 1216 mL/day, for Group C 64 +/- 1399 mL/day, 2586 +/- 1071 mL/day and
      2522 +/- 1048 mL/day and for Control Group -253 +/- 1495 mL/day, 2912 +/- 1025
      mL/day and 3492 +/- 2099 mL/day. Significant differences were detected in water
      balance, intake and loss (p < 0.01). Water balance and water intake in Group A
      was the lowest. For Groups A, B, C and Control, contribution of solid foods to
      water intake was 36%, 29%, 32%, 25%, of drinking water was 32%, 48%, 45%, 47%, of
      beverages was 32%, 23%, 23% and 28% respectively. Significant differences
      observed in the contribution of drinking water and beverages (p < 0.01). Group A
      had lower water balance and water intake. Groups B and C had lower water intake
      from beverages.

PMID- 29576372
TI  - A novel composite adaptive flap controller design by a high-efficient modified
      differential evolution identification approach.
AB  - The optimal tuning of adaptive flap controller can improve adaptive flap control
      performance on uncertain operating environments, but the optimization process is
      usually time-consuming and it is difficult to design proper optimal tuning
      strategy for the flap control system (FCS). To solve this problem, a novel
      adaptive flap controller is designed based on a high-efficient differential
      evolution (DE) identification technique and composite adaptive internal model
      control (CAIMC) strategy. The optimal tuning can be easily obtained by DE
      identified inverse of the FCS via CAIMC structure. To achieve fast tuning, a high
      efficient modified adaptive DE algorithm is proposed with new mutant operator and
      varying range adaptive mechanism for the FCS identification. A tradeoff between
      optimized adaptive flap control and low computation cost is successfully achieved
      by proposed controller. Simulation results show the robustness of proposed method
      and its superiority to conventional adaptive IMC (AIMC) flap controller and the
      CAIMC flap controllers using other DE algorithms on various uncertain operating
      conditions. The high computation efficiency of proposed controller is also
      verified based on the computation time on those operating cases.

PMID- 29576373
TI  - Dual-stage periodic event-triggered output-feedback control for linear systems.
AB  - This paper proposes an event-triggered control framework, called dual-stage
      periodic event-triggered control (DSPETC), which unifies periodic event-triggered
      control (PETC) and switching event-triggered control (SETC). Specifically, two
      period parameters h1 and h2 are introduced to characterize the new event
      triggering rule, where h1 denotes the sampling period, while h2 denotes the
      monitoring period. By choosing some specified values of h2, the proposed control
      scheme can reduce to PETC or SETC scheme. In the DSPETC framework, the controlled
      system is represented as a switched system model and its stability is analyzed
      via a switching-time-dependent Lyapunov functional. Both the cases with/without
      network-induced delays are investigated. Simulation and experimental results show
      that the DSPETC scheme is superior to the PETC scheme and the SETC scheme.

PMID- 29576374
TI  - Prediction of vesicoureteral reflux in children with febrile urinary tract
      infection using relative uptake and cortical defect in DMSA scan.
AB  - BACKGROUND: Vesicoureteral reflux (VUR) is an important urologic anomaly that
      causes renal injury in children with febrile urinary tract infection (UTI). The
      present study aimed to evaluate the associations of abnormalities detected on
      technetium-99m-labeled dimercaptosuccinic acid (DMSA) scans, focusing on the
      association with VUR of the levels of relative decrease in kidney function and
      cortical defects after a first febrile UTI in children. METHODS: All 171 children
      underwent ultrasonography, DMSA scan and voiding cystourethrography (VCUG). The
      features of ultrasound and DMSA scans were compared between patients with (n =
      48) and without VUR (n = 123). The relative uptake (RU) by each kidney was
      derived from the absolute value of the differences between the value for RU of
      radionuclide in the right kidney and that in the left kidney. The extent of
      cortical defects (ECD) was graded according to the number of compartments that
      contained cortical defect in both kidneys (right upper/right lower, left
      upper/left lower). Receiver operating characteristic curves were constructed to
      examine the diagnostic value of these parameters of ultrasound and DMSA scans for
      predicting VUR. RESULTS: The ratio of patients having hydronephrosis on
      ultrasound or cortical defects on DMSA scan did not differ significantly between
      VUR and non-VUR groups. However, the absolute values of the RU and the scores for
      ECD were significantly higher in the VUR group than in the non-VUR group. The
      area under the curves for these two parameters were higher than those for the
      presence of hydronephrosis or the presence of cortical defects or both.
      CONCLUSION: Decreased relative function and increased extents of cortical defects
      on DMSA scan may be associated with the presence of VUR. These findings may
      assist pediatricians to decide whether febrile UTI children need to undergo VCUG.

PMID- 29576377
TI  - Corrections.

PMID- 29576378
TI  - How far away the cornfield. Dennis Spencer's journey.

PMID- 29576376
TI  - Complex Interplay between Epitope Specificity and Isotype Dictates the Biological
      Activity of Anti-human CD40 Antibodies.
AB  - Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function
      hold promise as therapeutics for cancer and autoimmunity. Rules governing their
      diverse range of functions, however, are lacking. Here we determined
      characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40
      extracellular region expressed as varying isotypes. All mAb formats were strong
      agonists when hyper-crosslinked; however, only those binding the membrane-distal
      cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc
      gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic
      activity decreased as epitopes drew closer to the membrane. In addition, all CRD2
      4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus,
      the membrane distal CRD1 provides a region of choice for selecting CD40 agonists
      while CRD2-4 provides antagonistic epitopes.

PMID- 29576379
TI  - Frederik Barkhof: building bridges between disciplines.

PMID- 29576381
TI  - Use of degludec insulin in chronic complex patients.

PMID- 29576382
TI  - Re: "Early versus delayed closure of bladder exstrophy: A National Surgical
      Quality Improvement Program Pediatric analysis".

PMID- 29576380
TI  - Cultural influences on mental health symptoms in a primary care sample of Latinx
      patients.
AB  - The present study examines how both between group (i.e., ethnic group membership)
      and within group cultural factors (i.e., nativity status, age of immigration, and
      perceived discrimination) may contribute to anxiety and related symptoms in
      Latinx with anxiety disorders. Baseline data were examined from patients who
      participated in one of the largest intervention studies for adults with anxiety
      disorders in primary care settings; 196 Latinx and 568 NLW (non-Latinx White)
      patients participated. Proportions of anxiety disorders were similar between
      Latinx and NLWs; however, Latinx, on average, had a greater number of anxiety
      disorders than NLWs. Levels of anxiety and depression symptom severity, anxiety
      sensitivity, and mental functional impairment were similar between the ethnic
      groups. Latinx expressed greater somatization and physical functional impairment
      than NLWs. Among Latinx, perceived discrimination, but not other cultural
      variables, was predictive of mental health symptoms while controlling for age,
      gender, education, and poverty. Overall, these findings suggest more similarities
      than differences in types and levels of anxiety and anxiety-related impairment,
      with some important exceptions, including greater levels of somatization and
      physical functional impairment among Latinx patients. Further, perceived
      discrimination may be an important factor to consider when examining risk for
      greater symptom burden among Latinx with anxiety.

PMID- 29576375
TI  - Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
AB  - With the use of a mouse model expressing human Fc-gamma receptors (FcgammaRs), we
      demonstrated that antibodies with isotypes equivalent to ipilimumab and
      tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo,
      increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies
      with improved FcgammaR binding profiles drove superior anti-tumor responses and
      survival. In patients with advanced melanoma, response to ipilimumab was
      associated with the CD16a-V158F high affinity polymorphism. Such activity only
      appeared relevant in the context of inflamed tumors, explaining the modest
      response rates observed in the clinical setting. Our data suggest that the
      activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of
      FcgammaR binding, whereas poorly infiltrated tumors will likely require
      combination approaches.

PMID- 29576383
TI  - Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcoma.
AB  - Leiomyosarcomas (LMS) are rare tumors with poor prognosis owing to the high rate
      of recurrent and metastatic disease. The combination of doxorubicin (Adriamycin)
      plus ifosfamide and mesna (AIM) results in moderate response rates of 10%-30%.
      The aim of this study was to assess the efficacy of the AIM regimen along with
      multimodality treatment including surgery and radiotherapy in patients with LMS.
      The clinicopathologic characteristics and outcomes of 51 patients with recurrent
      or metastatic LMS diagnosed between 2000 and 2014 who received the AIM regimen
      were analyzed retrospectively. Treatment consisted of ifosfamide 2500mg/m2 on
      days 1-3 (with mesna 2500mg/m2 days 1-3, 4-hour i.v. infusion), and doxorubicin
      60mg/m2 on day 1 (2-hour i.v. infusion), which was repeated every 21 days. The
      mean age of the patients at diagnosis was 48.9 +/- 11.2 years. A total of 42
      patients were females (82.4%). The primary tumor site was the uterus in 30
      (58.8%) patients. The most common metastatic sites were lung and liver. The
      median follow-up was 27.9 months (min: 4.3 max: 164.8). The median progression
      free survival was 6.7 months (95% CI: 4.1-9.2). The median overall survival (OS)
      was 24.6 months (95% CI: 16.2-33.0). The overall response rate was 12% (6/51
      pts). Response rates were higher in patients with uterine LMS (17%) compared with
      those with nonuterine LMS (5%); however, the OS times were similar. Surgical
      intervention for local or distant recurrence was associated with improved median
      OS (41 vs 16.6 months, P < 0.001). Myelosuppression was the major toxicity of
      this combination. In our study, the AIM regimen was effective in patients with
      LMS. Resection of local or distant recurrence was found to improve survival in
      our study.

PMID- 29576384
TI  - Assessing social-pragmatic inferencing skills in children with autism spectrum
      disorder.
AB  - By utilizing the Pragma test this study investigated how sixteen five- to ten
      year-old children with autism spectrum disorder (ASD) and sixteen typically
      developing (TD) children comprehended contextually challenging scenarios
      demanding 1) contextual inference with theory of mind (ToM), 2) contextual
      inference without ToM, 3) relevant use of language, 4) recognition of feelings,
      and 5) understanding false beliefs. The study also compared children's ability to
      explain their own correct answers. In addition, this study evaluated the
      sensitivity of three different methods for discriminating the children with ASD
      from the TD children: 1) the Pragma test, 2) the Social Interaction Deviance
      Composite (SIDC) of Children's Communication Checklist-2 (CCC-2), and 3) the
      Theory of Mind subtest of the Developmental Neuropsychological Assessment, Second
      edition (NEPSY-II). The results showed that children with ASD differed from TD
      children in questions demanding context utilization. However, the demand of mind
      reading in utterance interpretation increased the difference between groups.
      Compared to TD children, children with ASD had more difficulties in explaining
      how they had used context to arrive at the correct answer. The discrimination
      power for detecting children with ASD from TD children was excellent in the
      Pragma test, good in the SIDC CCC-2 and fair in the Theory of Mind subtest of
      NEPSY-II. This study showed that by using contextually sensitive materials, such
      as the Pragma test, it is possible to detect the social-pragmatic inferencing
      difficulties of high-functioning children with ASD in structured test situations
      and not only in real-life situations or by using parental reports.

PMID- 29576385
TI  - Analysis of morphological variability and heritability in the head of the
      Argentine Black and White Tegu (Salvator merianae): undisturbed vs. disturbed
      environments.
AB  - The heterogeneity of biotic and abiotic factors influencing fitness produce
      selective pressures that promote local adaptation and divergence among different
      populations of the same species. In order for adaptations to be maintained
      through evolutionary time, heritable genetic variation controlling the expression
      of the morphological features under selection is necessary. Here we compare
      morphological shape variability and size of the cephalic region of Salvator
      merianae specimens from undisturbed environments to those of individuals from
      disturbed environments, and estimated heritability for shape and size using
      geometric morphometric and quantitative genetics tools. The results of these
      analyzes indicated that there are statistically significant differences in shape
      and size between populations from the two environments. Possibly, one of the main
      determinants of cephalic shape and size is adaptation to the characteristics of
      the environment and to the trophic niche. Individuals from disturbed environments
      have a cephalic region with less shape variation and also have a larger centroid
      size when compared to individuals from undisturbed environments. The high
      heritability values obtained for shape and size in dorsal view and right side
      view indicate that these phenotypic characters have a great capacity to respond
      to the selection pressures to which they are subjected. Data obtained here could
      be used as an important tool when establishing guidelines for plans for the
      sustainable use and conservation of S. merianae and other species living in
      disturbed areas.

PMID- 29576386
TI  - Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual
      Meeting, 2017.
AB  - The novel clinical data for myeloma that were presented in the 2017 Annual
      Meeting of the American Society of Hematology are summarized here. Studies with
      curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for
      patients with high-risk smoldering multiple myeloma (SMM) are described. Updated
      data from large phase III studies for patients with newly diagnosed MM (NDMM) who
      are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are
      described, along with the results of studies using novel anti-myeloma drug
      combinations for induction, consolidation, and maintenance as first-line therapy.
      The role of minimal residual disease for patients with MM is also discussed. We
      also present the results of novel phase III studies in patients with NDMM who are
      not eligible for ASCT (ALCYONE) and new data for their treatment. Recent updates
      of important studies in the field of relapsed/refractory MM (ASPIRE, POLLUX)
      along with novel immunotherapy approaches (anti-BCMA monoclonal antibodies, CART
      cells) are also reported. Finally, levofloxacin prophylaxis reduces febrile
      episodes and death events in NDMM, whereas 2 doses of high-dose influenza vaccine
      seem to maintain higher rates of seroprotection compared with those who received
      standard vaccination. All these data provide the basis for possible changes in
      the way we manage myeloma in the near future trying to "cure" the disease in many
      patients.

PMID- 29576387
TI  - Functional Divergence of Delta and Mu Opioid Receptor Organization in CNS Pain
      Circuits.
AB  - Cellular interactions between delta and mu opioid receptors (DORs and MORs),
      including heteromerization, are thought to regulate opioid analgesia. However,
      the identity of the nociceptive neurons in which such interactions could occur in
      vivo remains elusive. Here we show that DOR-MOR co-expression is limited to small
      populations of excitatory interneurons and projection neurons in the spinal cord
      dorsal horn and unexpectedly predominates in ventral horn motor circuits.
      Similarly, DOR-MOR co-expression is rare in parabrachial, amygdalar, and cortical
      brain regions processing nociceptive information. We further demonstrate that in
      the discrete DOR-MOR co-expressing nociceptive neurons, the two receptors
      internalize and function independently. Finally, conditional knockout experiments
      revealed that DORs selectively regulate mechanical pain by controlling the
      excitability of somatostatin-positive dorsal horn interneurons. Collectively, our
      results illuminate the functional organization of DORs and MORs in CNS pain
      circuits and reappraise the importance of DOR-MOR cellular interactions for
      developing novel opioid analgesics.

PMID- 29576389
TI  - Inter-areal Balanced Amplification Enhances Signal Propagation in a Large-Scale
      Circuit Model of the Primate Cortex.
AB  - Understanding reliable signal transmission represents a notable challenge for
      cortical systems, which display a wide range of weights of feedforward and
      feedback connections among heterogeneous areas. We re-examine the question of
      signal transmission across the cortex in a network model based on mesoscopic
      directed and weighted inter-areal connectivity data of the macaque cortex. Our
      findings reveal that, in contrast to purely feedforward propagation models, the
      presence of long-range excitatory feedback projections could compromise stable
      signal propagation. Using population rate models as well as a spiking network
      model, we find that effective signal propagation can be accomplished by balanced
      amplification across cortical areas while ensuring dynamical stability. Moreover,
      the activation of prefrontal cortex in our model requires the input strength to
      exceed a threshold, which is consistent with the ignition model of conscious
      processing. These findings demonstrate our model as an anatomically realistic
      platform for investigations of global primate cortex dynamics.

PMID- 29576388
TI  - Glycinergic Inhibitory Plasticity in Binaural Neurons Is Cumulative and Gated by
      Developmental Changes in Action Potential Backpropagation.
AB  - Utilization of timing-based sound localization cues by neurons in the medial
      superior olive (MSO) depends critically on glycinergic inhibitory inputs. After
      hearing onset, the strength and subcellular location of these inhibitory inputs
      are dramatically altered, but the cellular processes underlying this experience
      dependent refinement are unknown. Here we reveal a form of inhibitory long-term
      potentiation (iLTP) in MSO neurons that is dependent on spiking and synaptic
      activation but is not affected by their fine-scale relative timing at higher
      frequencies prevalent in auditory circuits. We find that iLTP reinforces
      inhibitory inputs coactive with binaural excitation in a cumulative manner,
      likely well suited for networks featuring persistent high-frequency activity. We
      also show that a steep drop in action potential size and backpropagation limits
      induction of iLTP to the first 2 weeks of hearing. These intrinsic changes would
      deprive more distal inhibitory synapses of reinforcement, conceivably
      establishing the mature, soma-biased pattern of inhibition.

PMID- 29576391
TI  - Improving the Value of Clinical Quality Registries Through Data Linkage.

PMID- 29576390
TI  - Role for Wnt Signaling in Retinal Neuropil Development: Analysis via RNA-Seq and
      In Vivo Somatic CRISPR Mutagenesis.
AB  - Screens for genes that orchestrate neural circuit formation in mammals have been
      hindered by practical constraints of germline mutagenesis. To overcome these
      limitations, we combined RNA-seq with somatic CRISPR mutagenesis to study synapse
      development in the mouse retina. Here synapses occur between cellular layers,
      forming two multilayered neuropils. The outer neuropil, the outer plexiform layer
      (OPL), contains synapses made by rod and cone photoreceptor axons on rod and cone
      bipolar dendrites, respectively. We used RNA-seq to identify selectively
      expressed genes encoding cell surface and secreted proteins and CRISPR-Cas9
      electroporation with cell-specific promoters to assess their roles in OPL
      development. Among the genes identified in this way are Wnt5a and Wnt5b. They are
      produced by rod bipolars and activate a non-canonical signaling pathway in rods
      to regulate early OPL patterning. The approach we use here can be applied to
      other parts of the brain.

PMID- 29576392
TI  - Clinical outcome and cerebrospinal fluid profiles in patients with tick-borne
      encephalitis and prior vaccination history.
AB  - BACKGROUND: Tick-borne encephalitis (TBE) is endemic in southern and eastern
      districts of Germany. Approximately 10-14% of the infected individuals suffer
      from long-term disability and in 1.5-3.6% the course is fatal. Two well-tolerated
      vaccines are available, which provide high protection and which have been
      confirmed in several field studies. Here we investigate clinical course, long
      term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a
      prior history of any vaccination as well as real vaccination breakthrough (VBT).
      METHODS: A case series of 11 patients with a prior history of vaccination, part
      of a recently published lager cohort of 111 TBE cases. Evaluation included
      clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of
      CSF and serum samples. Furthermore, metadata for extended analysis on clinical
      outcome of TBE with VBT were analysed. RESULTS: One patient had a clear VBT and
      ten of them had irregular vaccinations schedules (IVS). Infection severity did
      not differ in patients with IVS as compared to a non-vaccinated control cohort
      (median mRS: both 3.0) but these patients showed a stronger cellular immune
      response as measured by CSF pleocytosis (IVS, 205 cells/MUL versus non-vaccinated
      control, 114 cell/MUL, P < 0.05) and by differential pattern of CSF (intrathecal)
      immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by
      linear association revealed a more serious course of TBE in patients with VBT
      than in a non-vaccinated control cohort (chi2 = 9.95, P = 0.002). Furthermore,
      ordinal logistic regression analysis showed that VBT patients had an age
      corrected, 2.65 fold (CI: 1.110-6.328; chi2 = 4.813; p = 0.028) significant
      higher risk to suffer from moderate or severe infections, respectively.
      CONCLUSION: A history of IVS surprisingly seems to have no impact on the clinical
      course of TBE but may leave marks in the specific brain immune response. VBT
      patients, however, carry an age-independent, significant risk to experience a
      severe infection.

PMID- 29576393
TI  - Peroxiredoxins are important for the regulation of hydrogen peroxide
      concentrations in ticks and tick cell line.
AB  - Ticks are obligate hematophagous ectoparasites, as they need to feed blood from
      vertebrate hosts for development. Host blood contains high levels of iron. Host
      derived iron may lead to high levels of reactive oxygen species (ROS), including
      hydrogen peroxide (H2O2). Since a high concentration of H2O2 causes serious
      damage to organisms, this molecule is known to be a harmful chemical compound for
      aerobic organisms. On the other hand, the transparent method is compatible with
      chemical fluorescent probes. Therefore, we tried to establish the visualizing
      method for H2O2 in unfed tick tissues. The combination method of a chemical
      fluorescent probe (BES-H2O2-Ac) with the transparent method, Scale, demonstrated
      in unfed tick tissues that H2O2 and paraquat could induce oxidative stress in the
      tissues, such as the midgut and ovary. In addition, an H2O2 detection method
      using BES-H2O2-Ac was established in Ixodes scapularis embryo-derived cell line
      (ISE6) in vitro to evaluate the antioxidant activity of peroxiredoxins (PRXs),
      H2O2 scavenging enzymes, against H2O2 in the cells. The effects of paraquat in
      ISE6 cells were also observed in the PRXs gene-silenced ISE6 cells. A high
      intensity of H2O2 fluorescence induced by paraquat was observed in the PRX gene
      knockdowned cells. These results suggest that H2O2 and paraquat act as an H2O2
      inducer, and PRX genes are important for the regulation of the H2O2 concentration
      in unfed ticks and ISE6 cells. Therefore, this study contributes to the search
      for H2O2 visualization in ticks and tick cell line and furthers understanding of
      the tick's oxidative stress induced by H2O2.

PMID- 29576394
TI  - Characterization of a beta2 adrenergic receptor protein precursor in the European
      eel (Anguilla anguilla) and its tissue distribution across silvering.
AB  - This study provides the characterization and tissue distribution of a beta2-AR in
      the female European eel during silvering, aiming to better understand the
      adrenergic system involvement in this critical maturation event. A putative beta2
      AR (ADRB2) mRNA was cloned and sequenced. Amino acid residues and motifs
      important for ligand binding are generally conserved across fish and between fish
      and mammals, although the occurrence of some sequence variabilities may explain
      the noted peculiarities of eel AR interaction with pharmacological ligands. The
      tissue distribution of the ADRB2 gene product was analyzed in five tissues of the
      eel at different silvering stages and compared with that of the ADRA1 mRNA
      encoding an alpha1-AR subtype. On the whole, data suggested that relative
      ADRA1/ADRB2 tissue expression across silvering is part of the preparatory
      (molecular) adjustments required to face changes in habitats and migration
      efforts.

PMID- 29576395
TI  - Effect of an acrylic terpolymer barrier film beneath transparent catheter
      dressings on skin integrity, risk of dressing disruption, catheter colonisation
      and infection.
AB  - OBJECTIVES: We assessed the effect of a skin-protective terpolymer barrier film
      around the catheter insertion site on frequency of dressing disruptions and skin
      integrity issues (hyperaemia, skin irritation, residues of adhesives and moisture
      under the dressing). Secondary outcomes included colonisation of the central
      venous catheter (CVC) and rates of central line-associated bloodstream infection.
      RESEARCH METHODOLOGY: A monocentric, open-label, randomised controlled trial was
      performed comparing a control group receiving standard transparent catheter
      dressings without the skin-protecting barrier film and an intervention group
      receiving a transparent chlorhexidine-impregnated dressing with use of the skin
      protective acrylic terpolymer barrier film (3MTM CavilonTM No - Sting Barrier
      Film, 3 M Health Care, St. Paul, MN, USA). RESULTS: Sixty patients were enrolled
      and randomised in the study accounting for 60 central venous catheters and a
      total of 533 catheter days. Dressing disruptions occurred more frequently and at
      sooner time point in the control group. Skin integrity issues were significantly
      less observed in the intervention group. No differences in CVC colonisation or
      central line-associated bloodstream infection were observed. CONCLUSIONS: The
      application of a barrier film creating a skin-protective polymer layer beneath
      transparent catheter dressings is associated with less dressing disruptions and
      skin integrity issues without altering the risk of infectious complications if
      used in combination with a chlorhexidine-impregnated catheter dressing.

PMID- 29576396
TI  - Ancestry estimation of three Mediterranean populations based on cranial metrics.
AB  - The estimation of ancestry is an essential benchmark for positive identification
      of heavily decomposed bodies that are recovered in a variety of death and crime
      scenes. This is especially true when reconstructing the biological profile of the
      deceased as most methods for sex, age and stature estimation are population
      specific. Ancestry estimation methods vary from traditional morphological
      assessment of cranial features and biometric quantification to computer-aided
      shape analysis and classification with specialised software. The current paper
      aims to explore population differences between three neighbouring countries
      (Greece, Cyprus and Turkey) that have been in constant interaction through
      conflicts and population movements from the ancient past to the present day,
      through cranial measurements. The sample consists of 160 dry crania of Greek
      origin, 137 dry crania of Greek-Cypriot of origin Cyprus and 380 CT scans from
      Turks individuals. Twelve measurements were taken in both dry and virtual skulls.
      Data were submitted to principal component analysis and discriminant function
      analysis. Intra- and inter-observer error as well as the measurement error
      between virtual and physical measurements were quantified using TEM, rTEM and R.
      Measurement error was very low in all cases. Classification accuracy for cross
      validated data ranged from 74.1 to 97.9%. The highest accuracy was obtained for
      the Turks sample both in males and females. The results are in accordance with
      genetic data on the three populations. These results create great confidence in
      the application of the produced functions in forensic cases requiring ancestry
      estimation in Cyprus, specifically to unidentified individuals from the 1974
      conflict. In addition, these standards can be applied in other forensic
      situations where ethnicity is an issue but the geographic area of origin is
      limited to the area encompassing Turkey, Cyprus and Greece.

PMID- 29576397
TI  - Visual Rating Scales of White Matter Hyperintensities and Atrophy: Comparison of
      Computed Tomography and Magnetic Resonance Imaging.
AB  - GOAL: Magnetic resonance imaging (MRI) is the preferred modality for research on
      structural age-related brain changes. However, computed tomography (CT) is widely
      available and has practical and cost advantages over MRI for large-scale brain
      imaging research studies in acutely unwell patients. However, the relationships
      between MRI and CT measures of white matter hyperintensities (WMH) and atrophy
      are unclear. We examined the relationships between visual ratings of WMH,
      atrophy, and old infarcts in patients who had both CT and MRI scans. MATERIALS
      AND METHODS: Patients who had both CT and MRI scans in the International Stroke
      Trial-3 were studied. In both modalities, 2 raters independently completed
      standardized visual rating scales for WMH, and for central and superficial
      atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts
      according to size and location. FINDINGS: Seventy patients with a mean age of 69
      years were studied. There were moderate to substantial intrarater CT-MRI
      agreements for periventricular components of WMH scales (weighted Kappaappa = .55
      .75). Agreements for basal ganglia ratings were lower (weighted Kappaappa = .18
      .44), partly because of the misclassification of prominent perivascular spaces.
      Atrophy scales showed moderate to substantial CT-MRI agreements (weighted
      Kappaappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts
      and cavitated lesions. CONCLUSIONS: Standardized visual rating scales of white
      matter lesions and atrophy mostly show substantial agreement between CT and MRI.
      Clinical CT scans have a strong potential for wider exploitation in research
      studies, particularly in acutely unwell populations.

PMID- 29576398
TI  - Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous
      Speech.
AB  - BACKGROUND: Aphasia is one of the most devastating stroke-related consequences
      for social interaction and daily activities. Aphasia recovery in acute stroke
      depends on the degree of reperfusion after thrombolysis or thrombectomy. As
      aphasia assessment tests are often time-consuming for patients with acute stroke,
      physicians have been developing rapid and simple tests. The aim of our study is
      to evaluate the improvement of language functions in the earliest stage in
      patients treated with thrombolysis and in nontreated patients using our rapid
      screening test. MATERIALS AND METHODS: Our study is a single-center prospective
      observational study conducted at the Stroke Unit of the University Medical
      Hospital of Trieste (January-December 2016). Patients treated with thrombolysis
      and nontreated patients underwent 3 aphasia assessments through our rapid
      screening test (at baseline, 24 hours, and 72 hours). The screening test assesses
      spontaneous speech, oral comprehension of words, reading aloud and comprehension
      of written words, oral comprehension of sentences, naming, repetition of words
      and a sentence, and writing words. RESULTS: The study included 40 patients: 18
      patients treated with thrombolysis and 22 nontreated patients. Both groups
      improved over time. Among all language parameters, spontaneous speech was
      statistically significant between 24 and 72 hours (P value = .012), and between
      baseline and 72 hours (P value = .017). CONCLUSIONS: Our study demonstrates that
      patients treated with thrombolysis experience greater improvement in language
      than the nontreated patients. The difference between the 2 groups is increasingly
      evident over time. Moreover, spontaneous speech is the parameter marked by the
      greatest improvement.

PMID- 29576399
TI  - Chemical Diversity in the G Protein-Coupled Receptor Superfamily.
AB  - G protein-coupled receptors (GPCRs) are the largest family of cell signaling
      transmembrane proteins that can be modulated by a plethora of chemical compounds.
      Systematic cheminformatics analysis of structurally and pharmacologically
      characterized GPCR ligands shows that cocrystallized GPCR ligands cover a
      significant part of chemical ligand space, despite their limited number. Many
      GPCR ligands and substructures interact with multiple receptors, providing a
      basis for polypharmacological ligand design. Experimentally determined GPCR
      structures represent a variety of binding sites and receptor-ligand interactions
      that can be translated to chemically similar ligands for which structural data
      are lacking. This integration of structural, pharmacological, and chemical
      information on GPCR-ligand interactions enables the extension of the structural
      GPCR-ligand interactome and the structure-based design of novel modulators of
      GPCR function.

PMID- 29576400
TI  - Asymptomatic congenital lung malformations: Is nonoperative management a viable
      alternative?
AB  - INTRODUCTION: The purpose of this study was to evaluate clinical outcomes in
      children with asymptomatic congenital lung malformations (CLM) who were initially
      managed nonoperatively. METHODS: An IRB-approved retrospective review was
      performed on all CLMs at a single tertiary care referral center (Jan 2006-Dec
      2016, n=140). Asymptomatic cases that did not undergo elective resection were
      evaluated for subsequent CLM-related complications based on clinical records and
      a telephone quality of life survey. RESULTS: Out of 39 (27.9%) who were initially
      managed nonoperatively, 13 (33%) developed CLM-related symptoms and underwent
      surgical intervention at a median age of 6.8years (range, 0.7-19.8years). The
      most common indication for conversion to operative management was pneumonia
      (78%). Larger lesions, as measured by CT scan, were significantly associated with
      the need for subsequent surgical intervention (mean maximal diameter, 5.7 vs.
      2.9cm; p=0.005). Based on survey data with a median follow up of 3.9years (range,
      0.2-13.2years), 17% developed chronic pulmonary symptoms, including cough (11%)
      and asthma requiring bronchodilators (12%). CONCLUSION: Although these data
      support nonoperative management as a viable alternative to surgical resection, at
      least one-third of CLM children eventually develop pneumonia or other pulmonary
      symptoms. Larger lesions are correlated with an increased risk for eventual
      surgical resection. LEVEL OF EVIDENCE: Level IV.

PMID- 29576401
TI  - Longitudinal analysis of hospital charges following injury in a level 1 pediatric
      trauma system.
AB  - BACKGROUND: The treatment of injured children contributes substantially to the
      financial burden of a health care system. The purpose of this study was to
      characterize these charges at a level-1 pediatric trauma center. METHODS:
      Financial data for children (<14 years) admitted for traumatic injury from 1/2009
      to 12/2014 were analyzed. The charges of the index admission and first two years
      following discharge were evaluated. RESULTS: 5853 trauma patients were included
      with average annual charges of $11,128,730. The most common mechanisms of injury
      were fall (44%), sports (12%), and bike (9%). The median ISS was 6 (IQR 4-10)
      with a mortality rate of 1.8% and Z-score of 13.04 (p<0.001). The overall total
      charges per patient during the index admission were $9513. Spinal cord and major
      abdominal injuries had the greatest charges per patient ($55,560 and $23,618
      respectively) primarily owing to hospital LOS. During the first year after
      discharge, the total charges per patient were $1733, of which spinal cord injury
      resulted in highest overall ($19,426), owing to inpatient rehabilitation. For all
      other injury patterns, mean total charges per patient were $2376 (range $791
      $3573). CONCLUSIONS: The value proposition in health care requires us to define
      outcomes relative to costs. Injury severity, major injury location, and hospital
      length of stay are the highest contributors for the financial burden of pediatric
      traumatic injury, while inpatient readmissions and inpatient rehabilitation drove
      higher charges in the years following discharge. TYPE OF STUDY: Clinical Research
      Paper. LEVEL OF EVIDENCE: II - Cohort Study.

PMID- 29576403
TI  - A Survey of Wilderness Medicine Analgesia Practice Patterns.
AB  - INTRODUCTION: In 2014, the Wilderness Medical Society (WMS) published guidelines
      for the treatment of acute pain in remote settings. We surveyed wilderness
      medicine providers on self-reported analgesia prescribing practices. METHODS: We
      conducted a prospective, anonymous survey. Respondents were recruited from the
      WMS annual symposium in 2016. All willing attendees were included. RESULTS:
      During the symposium, we collected a total of 124 surveys (68% response rate).
      Respondent age was 42+/-12 (24-79) years (mean+/-SD with range), 58% were male,
      and 69% reported physician-level training. All respondents had medical training
      of varying levels. Of the physicians reporting a specialty, emergency medicine
      (59%, n=51), family medicine (13%, n=11), and internal medicine (8%, n=7) were
      reported most frequently. Eighty-one (65%) respondents indicated they prefer a
      standardized pain assessment tool, with the 10-point numerical rating scale being
      the most common (54%, n=67). Most participants reported preferring oral
      acetaminophen (81%, n=101) or nonsteroidal anti-inflammatory drugs (NSAID) (91%,
      n=113). Of those preferring NSAID, most reported administering acetaminophen as
      an adjunct (82%, n=101). Ibuprofen was the most frequently cited NSAID (71%,
      n=88). Of respondents who preferred opioids, the most frequently preferred opioid
      was oxycodone (26%, n=32); a lower proportion of respondents reported preferring
      oral transmucosal fentanyl citrate (9%, n=11). Twenty-five (20%, n=25)
      respondents preferred ketamine. CONCLUSIONS: Wilderness medicine practitioners
      prefer analgesic agents recommended by the WMS for the treatment of acute pain.
      Respondents most frequently preferred acetaminophen and NSAIDs.

PMID- 29576402
TI  - Genomic insight into the taxonomy of Rhizobium genospecies that nodulate
      Phaseolus vulgaris.
AB  - Due to the wide cultivation of bean (Phaseolus vulgaris L.), rhizobia associated
      with this plant have been isolated from many different geographical regions. In
      order to investigate the species diversity of bean rhizobia, comparative genome
      sequence analysis was performed in the present study for 69 Rhizobium strains
      mainly isolated from root nodules of bean and clover (Trifolium spp.). Based on
      genome average nucleotide identity, digital DNA:DNA hybridization, and
      phylogenetic analysis of 1,458 single-copy core genes, these strains were
      classified into 28 clusters, consistent with their species definition based on
      multilocus sequence analysis (MLSA) of atpD, glnII, and recA. The bean rhizobia
      were found in 16 defined species and nine putative novel species; in addition, 35
      strains previously described as Rhizobium etli, Rhizobium phaseoli, Rhizobium
      vallis, Rhizobium gallicum, Rhizobium leguminosarum and Rhizobium spp. should be
      renamed. The phylogenetic patterns of symbiotic genes nodC and nifH were highly
      host-specific and inconsistent with the genomic phylogeny. Multiple symbiovars
      (sv.) within the Rhizobium species were found as a common feature: sv. phaseoli,
      sv. trifolii and sv. viciae in Rhizobium anhuiense; sv. phaseoli and sv. mimosae
      in Rhizobium sophoriradicis/R. etli/Rhizobium sp. III; sv. phaseoli and sv.
      trifolii in Rhizobium hidalgonense/Rhizobium acidisoli; sv. phaseoli and sv.
      viciae in R. leguminosarum/Rhizobium sp. IX; sv. trifolii and sv. viciae in
      Rhizobium laguerreae. Thus, genomic comparison revealed great species diversity
      in bean rhizobia, corrected the species definition of some previously misnamed
      strains, and demonstrated the MLSA a valuable and simple method for defining
      Rhizobium species.

PMID- 29576404
TI  - Treatment outcomes in diabetic patients with chronic limb-threatening ischemia.
AB  - OBJECTIVE: There are conflicting reports about outcomes after infrainguinal
      bypass for chronic limb-threatening ischemia (CLTI) in patients with diabetes. We
      compared perioperative outcomes between patients with and patients without
      diabetes in the current era. METHODS: The National Surgical Quality Improvement
      Program vascular module, 2011 to 2014, was used to identify patients undergoing
      infrainguinal revascularization for CLTI. Patients with and without diabetes were
      compared in terms of presentation, comorbidities, operative approach, and 30-day
      outcomes. Major adverse limb events (MALEs) included 30-day major reintervention
      or amputation, and major adverse cardiovascular events (MACEs) included 30-day
      myocardial infarction, cardiac arrest, stroke, or death. Multivariable logistic
      regression was used to adjust for baseline differences. RESULTS: We identified
      8887 patients undergoing open (5744; 50% diabetic) or endovascular (3143; 62%
      diabetic) treatment for CLTI. Patients with diabetes were younger and more often
      nonwhite, nonsmokers, and obese. Patients with diabetes presented more often with
      tissue loss (71% vs 47%; P < .001) and were more likely to be treated with
      endovascular intervention (41% vs 29%; P < .001). The 30-day mortality was
      similar before (open, 3.1% vs 2.8% [P = .53]; endovascular, 2.6% vs 2.1% [P =
      .37]) and after adjustment for baseline differences (open: odds ratio [OR], 1.1
      [95% confidence interval (CI), 0.7-1.5]; endovascular: OR, 1.2 [95% CI, 0.7
      2.0]). Patients with diabetes had longer lengths of stay (open, 8 vs 6 days [P <
      .001]; endovascular, 3 vs 2 days [P < .001]) and higher 30-day readmission rates
      (open, 21% vs 18% [P < .01]; endovascular, 20% vs 15% [P < .01]); however, these
      differences were no longer significant after adjustment for baseline differences.
      Patients with diabetes had a higher rate of MACEs (7.0% vs 5.1%; P < .01) and
      lower rate of MALEs (8.1% vs 10%; P < .01) after bypass. After adjustment,
      patients with diabetes still had a lower rate of MALEs (OR, 0.7; 95% CI, 0.6-0.9)
      but no longer had a higher rate of MACEs (OR, 1.2; 95% CI, 0.9-1.6). CONCLUSIONS:
      CLTI patients with diabetes undergoing revascularization have similar 30-day
      outcomes compared with those without diabetes, although they appear to be at
      lower risk for MALEs after bypass. Prolonged length of stay and readmission in
      patients with diabetes is not due to underlying diabetic disease but likely
      secondary to other baseline comorbidities, such as higher rates of tissue loss.
      Concern for worse perioperative outcomes in patients with diabetes after lower
      extremity bypass is unsubstantiated and should not discourage a physician from
      performing an open bypass.

PMID- 29576405
TI  - A propensity-matched comparison of fenestrated endovascular aneurysm repair and
      open surgical repair of pararenal and paravisceral aortic aneurysms.
AB  - OBJECTIVE: This study investigated the outcomes of a current series of patients
      treated with fenestrated and branched endovascular aneurysm repair (F-BEVAR) or
      open surgical repair (OSR) for pararenal abdominal aortic aneurysms (pr-AAAs),
      including juxtarenal, suprarenal, and type IV thoracoabdominal aneurysms. This
      study compares the outcomes of these procedures from two high-volume centers
      without the bias induced by a learning curve. METHODS: All patients with pr-AAAs
      undergoing repair at two centers between January 2010 and June 2016 were included
      in a prospective database. Patients undergoing F-BEVAR and OSR were propensity
      matched for age, sex, anatomic criteria (aortic clamp site), coronary artery
      disease, chronic obstructive pulmonary disease, diabetes, smoking, chronic kidney
      disease, aneurysm diameter, and previous aortic surgery. The primary end points
      were mortality and dialysis. Secondary end points included any myocardial
      ischemia, respiratory and early procedural complications, acute kidney injury
      (AKI) according to RIFLE criteria (Risk, Injury, Failure, Loss of kidney
      function, and End-stage renal failure), spinal cord ischemia, a composite of
      these complications, and postoperative intensive care unit length of stay. During
      follow-up, all-cause survival and freedom from reintervention were compared, as
      was the patency of stented vessels and renal and visceral bypasses. Late renal
      function deterioration was evaluated. RESULTS: In this period, 157 F-BEVAR
      patients and 119 OSR patients were operated on. After 1:1 propensity matching,
      the study cohort consisted of 102 F-BEVARs and 102 OSRs. In the matched
      population, an average of 2.5 vessels were treated per patient. Univariate
      analysis demonstrated no significant difference in 30-day mortality (2.9% vs
      2.0%; P = .68), dialysis (4.9% vs 3.9%; P = 1), cardiac ischemic complications
      (3.8% vs 5.9%; P = .52), pulmonary complications (5.9% vs 5.9%; P = 1), or any
      complications (28.4% vs 30.4%; P = .63) in the F-BEVAR and OSR groups,
      respectively. AKI was significantly lower in the F-BEVAR group than in the OSR
      group (19.6% vs 52%; P < .001), as was severe AKI (>50% decrease in glomerular
      filtration rate, 6.9% vs 16.7%; P = .03). There was no spinal cord ischemia. The
      median intensive care unit length of stay was 1 day in both groups (P = .33).
      During follow-up, we found occlusions of five stented vessels and three surgical
      bypasses. Late renal function deterioration was comparable between the two
      groups. According to Kaplan-Meier estimates, all-cause survival at 24, 48, and 72
      months was 85.6%, 66.8%, and 55.8% after F-BEVAR and 90.5%, 82.9%, and 68.5%
      after OSR (P = .04). Rates of freedom from reintervention were 97.6% vs 97.5% at
      24 months, 90.1% vs 93.4% at 48 months, and 63.9% vs 93.4% at 72 months in the F
      BEVAR and OSR groups (P = .05), respectively. Thus, both all-cause survival and
      freedom from reintervention were lower in the F-BEVAR group. CONCLUSIONS: This
      propensity score analysis in patients with pr-AAA undergoing F-BEVAR or OSR
      suggests no difference in terms of 30-day mortality, dialysis, or organ-specific
      postoperative complications, with the exception of AKI. Postoperative AKI was
      significantly higher after OSR, although most patients had recovered before
      discharge. Our data suggest similar outcomes after F-BEVAR or OSR for pr-AAA.

PMID- 29576406
TI  - Screening of LDLR and APOB gene mutations in Mexican patients with homozygous
      familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder
      that causes accumulation of serum low-density lipoprotein cholesterol and
      premature cardiovascular disease. It is mainly related to mutations in the LDLR
      gene. Homozygous FH (HoFH) patients have the most severe form of the disease
      accounting for a worldwide prevalence of 1:1,000,000. In Mexico, at least 5 cases
      of HoFH have been reported. OBJECTIVE: The aim of this study was to describe the
      clinical, biochemical, and molecular data observed in patients with HoFH
      phenotype. METHODS: We included 13 patients, belonging to 11 families, with
      clinical and biochemical diagnoses suggestive of HoFH. Molecular analyses of the
      LDLR and APOB genes were performed by means of polymerase chain reaction followed
      by Sanger sequencing. RESULTS: The causal mutation of HoFH was found in 8 of 11
      unrelated patients. Excepting 1, all were true homozygotes. Six different
      variants in LDLR were identified: c.-139delCTCCCCCTGC, p.Glu140Lys, p.Asp360His,
      p.Asn405Lys, p.Ala755Glyfs*7, and p.Leu759Serfs*6. Of these, p.Asp360His and
      p.Asn405Lys were detected for the first time in Mexico; p.Leu759Serfs*6 showed to
      be the most frequent (43.7% of the alleles 7/16), and c.-139delCTCCCCCTGC is a
      new variant located in the promoter region. CONCLUSIONS: This work increases
      knowledge of biochemical and genetic features in Mexican patients with HoFH. A
      novel mutation in the LDLR gene promoter was detected: c.-139delCTCCCCCTGC, which
      possibly inhibits its expression.

PMID- 29576407
TI  - Treatment Patterns and Clinical Outcomes Among Metastatic Non-Small-Cell Lung
      Cancer Patients Treated in the Community Practice Setting.
AB  - INTRODUCTION: Multiple therapeutic options now exist for metastatic non-small
      cell lung cancer (mNSCLC). In this study we evaluated treatment patterns and
      outcomes in mNSCLC patients who received first-line (1L), second-line (2L), and
      third-line (3L) therapy. PATIENTS AND METHODS: A retrospective, observational
      cohort study was conducted using an electronic health record database of mNSCLC
      patients who received initial treatment from January 2012 through April 2016,
      with follow-up through June 2016. Patient characteristics and treatment patterns
      were characterized. Overall survival (OS) was assessed using the Kaplan-Meier
      method. RESULTS: We identified 10,689 1L patients. Median age was 68 years, and
      5816 (54%) were male. Most patients (6337; 59%) had a performance status of 1,
      and 8282 (77%) had nonsquamous histology. 1L treatment was chemotherapy in 9969
      (93%) patients, and targeted therapy in 685 (6%). Median OS (mOS) for all
      patients in 1L was 12.3 months (95% confidence interval [CI], 11.9-12.7), and
      24.3 months in 1L patients receiving targeted therapy. Among patients who
      received 2L therapy (n = 4235), 2790 (66%), 718 (17%), and 727 (17%) received
      chemotherapy, targeted therapy, and immunotherapy, respectively. mOS from 2L
      therapy was 9.6 months (95% CI, 9.1-10.1). In patients receiving 3L therapy (n =
      1580), 921 (58%), 355 (22%), and 304 (19%) received chemotherapy, targeted
      therapy, and immunotherapy, respectively. mOS from 3L therapy was 8.2 months (95%
      CI, 7.3-8.7). CONCLUSION: Targeted therapy and immunotherapy was most frequently
      used in the 2L and 3L setting during the study time frame. Survival differences
      observed according to treatment types are likely because of biologic differences,
      and suggest that patients with actionable mutations have a survival advantage.

PMID- 29576408
TI  - Insomnia and hypertension: A systematic review.
AB  - Insomnia is a prevalent sleep disorder that is associated with a multitude of
      health consequences. Particularly, insomnia has been associated with
      cardiovascular disease and its precursors, such as hypertension and blood
      pressure (BP) non-dipping. The present systematic review aimed to summarize the
      evidence on the concurrent and prospective associations between insomnia and
      hypertension and/or BP. Using electronic search engines (PubMed, SCOPUS,
      PsycINFO), 5,618 articles published from January 1970 to December 2017 were
      identified, and 64 met the inclusion criteria (26 to 162,121 participants; age
      range: 18-100; 46.4% male). Insomnia was based on diagnostic or non-diagnostic
      criteria. Hypertension was based on self-or physician-reports, antihypertensive
      medication use, and/or measured BP. Findings indicate that when insomnia is
      frequent, chronic, and/or accompanied with short sleep duration or objective
      markers of arousal, there is a strong association with hypertension/BP. Based on
      limited studies, hypertension did not significantly predict future insomnia in
      middle-aged adults, but did in older adults. Based on a majority of case-control
      studies, no differences in BP were found between participants with and without
      insomnia. Further research is needed to identify putative pathophysiological
      mechanisms underlying the link between insomnia and hypertension. The impact of
      insomnia therapy on BP should also be further examined in the future.

PMID- 29576409
TI  - The Impact of Sex on Alloimmunity.
AB  - Transplantation outcomes are known to be affected by multiple factors, including
      donor and recipient sex. Aside from the physiological characteristics of male and
      female donor allografts, accumulating evidence suggests that additional features
      underlie sex-specific immune responses that affect graft survival. We discuss
      here aspects of innate and adaptive alloimmunity that are specific to males and
      females in the context of underlying genetic and hormonal factors. These
      differences likely contribute to the observed disparities in graft survival.
      Understanding these features in more detail may lead to improved strategies for
      optimizing the results of organ transplantation.

PMID- 29576410
TI  - The effects of early trauma and the FKBP5 gene on PTSD and the HPA axis in a
      clinical sample of Gulf War veterans.
AB  - Previous research indicates that interactions between FKBP5 single nucleotide
      polymorphisms (SNPs) and child abuse are associated with posttraumatic stress
      disorder (PTSD) in adulthood. We examined the relationship between the T-allele
      of the rs1360780 FKBP5 SNP and child abuse on PTSD and the HPA axis in a clinical
      sample of Gulf War veterans. Genotyping was completed on 266 veterans and 174
      veterans additionally participated in a low dose dexamethasone suppression test
      (DST). The CAPS was used to determine PTSD status and the THQ was used to
      determine child abuse operationalized as either childhood physical or sexual
      abuse. Hierarchical regression models were used to assess FKBP5 * child abuse
      interactions on PTSD, basal cortisol levels, and post DST cortisol levels. The
      FKBP5 risk allele and child abuse were separately associated with PTSD diagnosis.
      The risk allele was also associated with significantly lower cortisol levels at
      baseline. However, no significant FKBP5 * child abuse interaction on PTSD
      diagnosis, basal cortisol levels, or greater cortisol suppression was observed.
      Our results suggest that FKBP5 may be a viable biomarker for PTSD. Nonetheless,
      further work will be required to reconcile our findings with previous reports of
      an FKBP5 * child abuse interaction on posttraumatic stress response.

PMID- 29576411
TI  - Are emotional action tendencies and attentional bias related to temperament
      dimensions in patients with borderline personality disorder?
AB  - Disturbances in emotion regulation have been identified as a core feature of
      patients with a borderline personality disorder (BPD). Findings of studies using
      experimental measures of emotion processing are mixed, which may be partially
      explained by the heterogeneity of the BPD population. To address this issue, we
      investigated differences in experimental measures of emotional action tendencies
      (approach-avoidance behaviour) and attentional bias to emotional stimuli in BPD
      subtypes. Data of the Approach-Avoidance Task (AAT) and the Emotional Stroop Task
      (EST) were collected in 140 BPD patients, previously clustered into four BPD
      subtypes based on temperament dimensions. We investigated (1) the relationship
      between temperament dimensions and the performance on the AAT and EST and (2)
      compared performance on these tasks in previous defined BPD subtypes. The results
      of the present study demonstrated a positive relationship between effortful
      control (EC) and AAT effect-scores. A higher level of EC was positively
      associated with a general emotional action tendency towards faces with directed
      gaze, even when controlling for gender, age and BPD severity. Preliminary results
      on the comparison of the BPD subtypes demonstrated no significant differences in
      AAT and EST performance. These findings emphasize the relevance of EC in
      emotional action tendencies in BPD patients.

PMID- 29576413
TI  - The effects of antipsychotics on the density of cannabinoid receptors in selected
      brain regions of male and female adolescent juvenile rats.
AB  - Antipsychotic drugs have been increasingly prescribed to children and adolescents
      for treating various mental disorders, such as childhood-onset schizophrenia. The
      abnormality of endocannabinoid system is involved in the pathophysiology of these
      disorders in juveniles. This study investigated the effect of antipsychotics on
      the cannabinoid (CB) receptors in the brain of both male and female juvenile
      rats. The postnatal rats (PD23+/-1) were administered aripiprazole (1 mg/kg),
      olanzapine (1 mg/kg), risperidone (0.3 mg/kg) or vehicle (control) for 3 weeks.
      Quantitative autoradiography was used to investigate the binding densities of
      [3H]CP-55940 (an agonist for CB1R and CB2R) and [3H]SR141716A (a selective CB1R
      antagonist) in the rat brains. Risperidone significantly upregulated the
      [3H]CP55940 and [3H]SR141716A bindings in the prefrontal cortex (PFC), nucleus
      accumbens core (NAcC), nucleus accumbens shell (NAcS), cingulate cortex (Cg), and
      the caudate putamen (CPu) in male rats. Moreover, aripiprazole significantly
      elevated the [3H]SR141716A binding in the Cg and NAcS of female rats.
      Furthermore, there is an overall higher [3H]SR141716A binding level in the brain
      of female rats than male rats. Therefore, treatment with aripiprazole, olanzapine
      and risperidone could induce differential and gender specific effects on the
      binding density of cannabinoid receptors in the selected brain regions of
      childhood/adolescent rats.

PMID- 29576412
TI  - Oppositional behavior and longitudinal predictions of early adulthood mental
      health problems in chronic tic disorders.
AB  - Chronic tic disorders (TD) are associated with a number of psychological problems
      such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive
      behavior (OCB), oppositional-defiant disorder (ODD) as well as anxious and
      depressive symptoms. ODD is often considered a risk factor for many psychological
      symptoms and recent work suggests that different ODD dimensions show independent
      predictions of later psychological problems. This study examined the longitudinal
      predictions between ODD dimensions of Irritability and Defiance and the most
      frequent comorbidities in TD from childhood to early adulthood. From an initial
      sample of 135, parent reports were obtained on 58 participants with TD using
      standard clinical questionnaires and semi-structured interviews. Defiance
      symptoms decreased from baseline to follow-up whereas Irritability symptoms were
      more stable over time. In multiple regressions, Irritability in childhood
      predicted anxiety and OCB in early adulthood while Defiance in childhood
      predicted ADHD and conduct disorder symptoms in early adulthood. No developmental
      link was found for depressive symptoms. Results indicate that ODD dimensions are
      developmentally linked to both internalizing and externalizing adult mental
      health symptoms in TD.

PMID- 29576414
TI  - Imaging and Pathologic findings of Hepatic Small Vessel Hemangioma.
AB  - Hepatic small vessel hemangioma represents a distinct yet very rare pathologic
      entity of the liver. The entity has also been in the past referred to as adult
      capillary hemangioma of the liver and congenital noninvoluting hemangioma.
      Imaging findings are not definitive and biopsy or resection is ultimately
      necessary. Pathologically these represent vasoformative abnormalities with
      infiltrative margins that can potentially mimic hepatic angiosarcoma.
      Immunohistochemistry can help differentiate hepatic small vessel hemangioma from
      angiosarcoma. Given the infiltrative growth pattern and unknown outcomes,
      resection and or close follow up has been recommended. Recently the term hepatic
      small vessel neoplasm has been coined in view of the unknown outcomes and some
      concerning findings on molecular analysis. We report 2 cases of this unusual
      entity and describe its imaging, gross pathologic, histopathologic, and
      immunohistochemical features.

PMID- 29576416
TI  - No impact of English national cancer policies on survival.

PMID- 29576415
TI  - Prevalence and Severity of Off-Centering During Diagnostic CT: Observations From
      57,621 CT scans of the Chest, Abdomen, and/or Pelvis.
AB  - PURPOSE: To determine distances between patient centroid and gantry isocenter
      during CT imaging of the chest, abdomen, and/or pelvis, and to evaluate
      differences based on patient gender, scan region, patient position, and gantry
      aperture. MATERIALS AND METHODS: A water phantom and an anthropomorphic phantom
      were imaged in the centered position in the CT gantry and at several off-centered
      positions. Additionally, data from 57,621 adult chest, abdomen, and/or pelvic CT
      acquisitions were evaluated. Data were analyzed with an analysis of variance
      using the centroid-to-isocenter data as the dependent variable and the other
      parameters as independent variables. RESULTS: The majority of patient
      acquisitions (83.7% (48271/57621)) were performed with the patient's centroid
      positioned below isocenter (mean 1.7 cm below isocenter (SD 1.8 cm); range 12.1
      cm below to 7.8 cm above isocenter). Off-centering in the x-axis was less severe
      (mean 0.01 cm left of isocenter (SD 1.6 cm)). Distance between centroid and
      isocenter in the y-axis did not differ as a function of sex but did differ based
      on scan region, patient position, and gantry aperture. CONCLUSION: Off-centering
      is common during CT imaging and has been previously demonstrated to impact dose
      and image quality.

PMID- 29576417
TI  - TACE plus external beam radiotherapy in liver cancer.

PMID- 29576418
TI  - Major health-care companies merge in the USA.

PMID- 29576419
TI  - Patterns of care and outcomes for glioblastoma in patients with poor performance
      status.
AB  - PURPOSE/OBJECTIVES: While treatment with tumor resection followed by
      chemoradiation is generally the accepted standard of care for glioblastoma (GBM),
      the treatment for patients with poor performance status remains uncertain.
      Therefore we sought to examine patterns of care and survival outcomes among
      patients with poor performance status utilizing a large hospital database.
      METHODS/MATERIALS: We queried the National Cancer Database (NCDB) for patients
      with GBM and Karnofsky performance status (KPS) <60 between 2010 and 2013. Data
      was collected regarding surgery, radiation therapy and chemotherapy. Logistic
      regression was used to analyze predictors for utilization of chemoradiation. The
      Kaplan-Meier method was used to compare survival between those who received
      chemoradiation to radiation alone and Cox regression was performed to assess
      covariates associated with survival. RESULTS: There were 488 patients included in
      the analysis of which 51.2% received chemoradiation and 46.1% underwent subtotal
      or gross total resection. None of the factors analyzed were significantly
      associated with increased likelihood of receiving chemoradiation over radiation
      alone. Survival data was available for 236 patients that received radiation
      therapy with and without combination chemotherapy. The median overall survival
      for those receiving radiation alone was 3.6 months and 8.7 months in those who
      received chemoradiation (p < 0.001). On multivariable Cox regression, increasing
      age (HR 1.80-2.10, p = 0.001) was associated with worse survival while
      subtotal/gross total resection (HR 0.60, p = 0.003) and chemoradiation (HR 0.57,
      CI 0.40-0.83, p = 0.003) were associated with improved survival. CONCLUSION: Even
      patients with poor performance status had better survival outcomes when they
      received treatment with chemoradiation over radiation alone.

PMID- 29576420
TI  - Why Graduate Medical Education Funding Matters.

PMID- 29576421
TI  - Image Wisely: Reflections of a Former Co-Chair.

PMID- 29576422
TI  - Late characterisation of cardiac effects following anthracycline and trastuzumab
      treatment in breast cancer patients.
AB  - BACKGROUND: Anthracycline (A) and trastuzumab (T) chemotherapy have well
      recognized cardiac toxicity, potentially leading to significant morbidity and
      mortality. Our previous work in 46 prospectively enrolled breast cancer patients
      showed early left ventricular (LV) and right ventricular (RV) function decline at
      1 and 3 months, but only persistent RV dysfunction at 12 months which correlated
      with myocardial oedema observed early (1 and 3 months) after administration of
      chemotherapy regimes. METHOD: To investigate late cardiac effects, the same
      cohort were re-imaged with advanced Cardiovascular Magnetic Resonance (CMR)
      imaging including T1 mapping 5 +/- 1 year post chemotherapy. RESULTS: Twenty-six
      out of 46 (50%) patients underwent follow-up imaging. A statistical but non
      clinically significant decrease was observed in LV ejection fraction (EF) from
      baseline to 5 years (72.2 +/- 6.6 to 65.4 +/- 9.3, p < 0.005). Subjects with
      initial drop of LVEF by >10% at 3 months (n = 5) or at 12 months (n = 3) did not
      demonstrate any difference in LV or RVEF at 5 years. No correlation was observed
      between myocardial oedema and LV or RVEF at 5 years. At 5 years, T1 values were
      within normal limits overall (935 +/- 48 ms). One patients had significantly
      elevated (>1000 ms) T1 values with no correlation to LV or RVEF. No subjects
      demonstrated replacement myocardial fibrosis at 5 years. CONCLUSION: Using
      advanced CMR, contemporary chemotherapy regimes demonstrate minimal long-term
      cardiac toxicity. There is minimal diffuse and no replacement fibrosis as
      demonstrated by LGE, following chemotherapy. This study suggests limiting serial
      imaging in these patients at 12 months post chemotherapy.

PMID- 29576423
TI  - Iatrogenic pathology of the urinary bladder.
AB  - Intravesical immunotherapy, chemotherapy, and neoadjuvant systemic chemotherapy
      are among the most frequent therapeutic procedures to treat malignancies of the
      urinary bladder. These treatment modalities produce reactive morphologic changes
      in the urothelium that can mimic urothelial carcinoma in situ, urothelial
      dysplasia or true invasive urothelial neoplasia. Mitomycin C used after
      transurethral resection of bladder tumor to reduce recurrences, BCG intravesical
      immunotherapy to treat high risk non-muscle invasive bladder cancer and
      urothelial carcinoma in situ, and platinum-based systemic chemotherapy to improve
      post-cystectomy disease-specific survival some of the causes of therapy related
      atypia in urinary bladder. In addition, a number of systemic drugs in use to
      treat other systemic diseases, such as cyclophosphamide used to treat certain
      auto-immune disorders or hematologic malignancies, or the anesthetics ketamine
      increasingly used as illegal recreational drug, may produce similarly relevant
      atypical changes in the urothelium, and therefore, need to be differentiated from
      intraepithelial neoplasia. Immunohistochemical approach to reactive urothelium
      from CIS using CK20, p53, and CD44 may also be of utility in the pos-therapy
      scenario.

PMID- 29576424
TI  - A Temporal Transcriptional Switch Governs Stem Cell Division, Neuronal Numbers,
      and Maintenance of Differentiation.
AB  - The importance of producing the correct numbers of neurons during development is
      illustrated by both evolutionary enhancement of cognitive capacities in larger
      brains, and developmental disorders of brain size. In humans, increased neuronal
      numbers during development is speculated to partly derive from a unique subtype
      of neural stem cells (NSCs) that undergo a phase of expansion through symmetric
      self-amplifying divisions before generating neurons. Symmetric amplification also
      appears to underlie adult neural stem maintenance in the mouse. However, the
      mechanisms regulating this behavior are unclear. We report the discovery of self
      amplifying NSCs in Drosophila and show that they arise by a spatiotemporal
      conversion of classical self-renewing NSCs. This conversion is regulated by a
      temporal transition in the expression of proneural transcription factors prior to
      cell division. We find a causal link between stem cell self-amplification and
      increased neuronal numbers. We further show that the temporal transcriptional
      switch controls both stem cell division and subsequent neuronal differentiation.

PMID- 29576425
TI  - The Circadian Clock Sets the Time of DNA Replication Licensing to Regulate Growth
      in Arabidopsis.
AB  - The circadian clock and cell cycle as separate pathways have been well documented
      in plants. Elucidating whether these two oscillators are connected is critical
      for understanding plant growth. We found that a slow-running circadian clock
      decelerates the cell cycle and, conversely, a fast clock speeds it up. The clock
      component TOC1 safeguards the G1-to-S transition and controls the timing of the
      mitotic cycle at early stages of leaf development. TOC1 also regulates somatic
      ploidy at later stages of leaf development and in hypocotyl cells. The S-phase is
      shorter and delayed in TOC1 overexpressing plants, which correlates with the
      diurnal repression of the DNA replication licensing gene CDC6 through binding of
      TOC1 to the CDC6 promoter. The slow cell-cycle pace in TOC1-ox also results in
      delayed tumor progression in inflorescence stalks. Thus, TOC1 sets the time of
      the DNA pre-replicative machinery to control plant growth in resonance with the
      environment.

PMID- 29576426
TI  - A Pilot Study of Apatinib as Third-Line Treatment in Patients With Heavily
      Treated Metastatic Colorectal Cancer.
AB  - BACKGROUND: Antiangiogenic therapy has shown improved clinical outcome in
      metastatic colorectal cancer (mCRC). After the failure of standard treatments,
      regorafenib and TAS-102 would be recommended for patients with mCRC, however,
      they have not been approved in China during this study period. PATIENTS AND
      METHODS: This pilot study aimed to assess the efficacy and safety of apatinib, a
      novel oral inhibitor targeting vascular endothelial growth factor receptor 2, as
      third-line treatment for patients with mCRC refractory to standard therapies. In
      this retrospective study, all patients received apatinib treatment until
      progressive disease (PD), death, unacceptable toxicity, and curative surgery. The
      dose or treatment schedule was modified according to the physician's discretion
      according to the toxicity profiles. RESULTS: Between March 2015 and June 2017, 36
      patients were enrolled and eligible for evaluation of the safety and efficacy.
      One patient (2.8%) achieved complete response, 3 (8.3%) achieved partial
      response, 24 (66.7%) achieved stable disease, and 8 (22.2%) PD. The objective
      response rate and the disease control rate were 11.1% (4 of 36), and 77.8% (28 of
      36), respectively. Moreover, the median overall survival (OS) since the
      initiation of first-line treatment was 33.2 months. The median progression-free
      survival (PFS) and median OS from apatinib treatment were 4.8 and 10.1 months,
      respectively. Intergroup analysis showed that there was no significant difference
      in median PFS and median OS between patients who were previously treated with and
      without bevacizumab. The most common Grade 3 to 4 adverse reactions were hand
      foot syndrome, hypertension, and proteinuria. CONCLUSION: Our results suggested
      that apatinib was active as a third-line treatment of refractory mCRC with a
      manageable tolerability profile. In addition, preliminary data suggested that the
      efficacy of apatinib would not be affected by previous bevacizumab treatment.
      Further prospective randomized controlled clinical trials are urgently needed.

PMID- 29576427
TI  - Dermatologic Toxicity Occurring During Anti-EGFR Monoclonal Inhibitor Therapy in
      Patients With Metastatic Colorectal Cancer: A Systematic Review.
AB  - Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR)
      have been shown to improve outcomes for patients with metastatic colorectal
      cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR
      agents can be associated with toxicities of the skin, nails, hair, and eyes.
      Because these dermatologic toxicities can result in treatment discontinuation and
      affect patient quality of life, their management is an important focus when
      administering anti-EGFR monoclonal antibodies. The present systematic review
      describes the current data reporting the nature and incidence of, and management
      and treatment options for, dermatologic toxicities occurring during anti-EGFR
      treatment of mCRC. A search of the National Library of Medicine PubMed database
      from January 1, 2009, to August 18, 2016, identified relevant reports discussing
      dermatologic toxicity management among patients with mCRC receiving anti-EGFR
      therapy. The studies were grouped by type and rated by level of evidence using
      the GRADE approach developed by the Agency for Healthcare Research and Quality.
      Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized
      trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic
      toxicity of any grade occurs in most patients who receive anti-EGFR therapy;
      approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most
      common dermatologic toxicities include papulopustular/acneiform rash, xerosis,
      and pruritus; however, nail changes, hair abnormalities, and ocular conditions
      also occur. Guidance for managing these toxicities includes the use of
      inexpensive emollient ointments and moisturizers, avoidance of sun exposure,
      avoidance of irritants, and the use of short showers. Several studies also found
      that preemptive treatment was more effective than reactive treatment at limiting
      the incidence and severity of skin toxicity. With appropriate treatment, the
      dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can
      be managed, minimizing patient discomfort and the need for therapy interruption
      and/or discontinuation. Additionally, preemptive treatment can reduce
      dermatologic toxicity severity, ultimately yielding better quality of life.

PMID- 29576428
TI  - c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.
AB  - INTRODUCTION: Increased mesenchymal-epithelial transition factor gene (c-MET)
      expression in several human malignancies is related to increased tumor
      progression and is a new potential drug target for several types of cancers. In
      the present study, we investigated the incidence of c-MET overexpression and its
      prognostic significance in patients with colorectal cancer (CRC). PATIENTS AND
      METHODS: We retrospectively reviewed the data from 255 stage IV CRC patients who
      had results from a c-MET immunohistochemical test at Samsung Medical Center. We
      explored the relationships between c-MET overexpression and clinicopathological
      features and survival. RESULTS: Primary tumor sites were 67 right-sided colon, 98
      left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly
      differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%)
      exhibited c-MET overexpression. There was no significant difference in the
      prevalence of c-MET overexpression according to primary site, histologic
      differentiation, molecular markers, or metastatic sites. In a comparison of the
      tumor response to first-line chemotherapy according to the level of c-MET
      expression, we found no significant difference in either partial response or
      disease control rate. In the survival analysis, patients with c-MET
      overexpression had significantly shorter overall survival (39 vs. 27 months; P =
      .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7
      months; P = .024). CONCLUSION: c-MET overexpression, which was detected in 39 CRC
      patients (15.3%) irrespective of primary sites or molecular markers, indicated a
      poor survival prognosis and predicted shorter PFS during bevacizumab treatment in
      patients with CRC. Further studies are warranted to elucidate the value of c-MET
      targeted therapy in CRC patients.

PMID- 29576429
TI  - Continuous Variation within Cell Types of the Nervous System.
AB  - The brain is an organ of immense complexity. Next-generation RNA sequencing (RNA
      seq) is becoming increasingly popular in the deconstruction of this complexity
      into distinct classes of 'cell types'. Notably, in addition to revealing the
      organization of this distinct cell-type landscape, the technology has also begun
      to illustrate that continuous variation can be found within narrowly defined cell
      types. Here we summarize the evidence for graded transcriptomic heterogeneity
      being present, widespread, and functionally relevant in the nervous system. We
      explain how these graded differences can map onto higher-order organizational
      features and how they may reframe existing interpretations of higher-order
      heterogeneity. Ultimately, a multimodal approach incorporating continuously
      variable cell types will facilitate an accurate reductionist interpretation of
      the nervous system.

PMID- 29576430
TI  - Erectile Dysfunction and Associated Risk Factors in Chinese Males of Infertile
      Couples.
AB  - BACKGROUND: Knowledge on the occurrence of erectile dysfunction (ED) and timely
      ovulatory intercourse failure (TOIF) in Chinese men of infertile couples is
      limited. AIM: To obtain representative estimates of ED and TOIF in Chinese men of
      infertile couples and to analyze potential risk factors associated with ED.
      METHODS: 4,299 Chinese men of infertile couples with an average age of 32.85 +/-
      5.98 years were surveyed using the 5-item International Index of Erectile
      Function (IIEF-5) questionnaire for their ED occurrence. Multiple logistic
      regression analysis was used to disclose risk factors associated with ED.
      OUTCOMES: The occurrence of ED was 57.8% and that of TOIF was up to 26.2% in
      Chinese men of infertile couples. RESULTS: Based on IIEF-5 criteria, 34.9% of men
      had mild ED and only 2.6% had severe ED. Secondary infertility, infertility with
      known causes, and chronic prostatitis were significant risk factors associated
      with ED. TOIF was significantly higher (23.3%) in men of infertile couples with
      ED than in those without ED (8.6%), indicating that TOIF is likely a contributing
      factor to male infertility. CLINICAL IMPLICATIONS: Understanding the occurrence
      and types of ED and TOIF in men of infertile couples and their associated risk
      factors will help physicians treat clinical cases of male infertility more
      effectively. STRENGTHS AND LIMITATIONS: Large numbers of infertile outpatients
      from multiple hospital clinics across the country were included in this study.
      The concept of TOIF was raised for the 1st time and studied preliminarily in
      Chinese men of infertile couples. The lack of participants' psychological status,
      a control group of men of fertile couples, and measurement of testosterone levels
      was a limitation in this clinic-based study. CONCLUSION: The occurrence of ED was
      higher in Chinese men of infertile couples than in the general Chinese male
      population. Yang B, Xu P, Shi Y, et al. Erectile Dysfunction and Associated Risk
      Factors in Chinese Males of Infertile Couples. J Sex Med 2018;15:671-677.

PMID- 29576431
TI  - A Systematic Review of Sexual Distress Measures.
AB  - BACKGROUND: Sexual distress is an important component of sexual dysfunction and
      quality of life and many different measures have been developed for its
      assessment. AIM: To conduct a literature review of measures for assessing sexual
      distress and to list, compare, and highlight their characteristics and
      psychometric properties. METHODS: A systematic review was conducted using Scopus
      and PubMed databases to identify studies that developed and validated measures of
      sexual distress. The main characteristics and psychometric properties of each
      measure were extracted and examined. OUTCOMES: Psychometrically validated
      measures of sexual distress and a summary of relative strengths and limitations.
      RESULTS: We found 17 different measures for the assessment of sexual distress. 4
      were standalone questionnaires and 13 were subscales included in questionnaires
      that assessed broader constructs. Although 5 measures were developed to assess
      sexual distress in the general population, most were developed and validated in
      very specific clinical groups. Most followed adequate steps in the development
      and validation process and have strong psychometric properties; however, several
      limitations were identified. CLINICAL TRANSLATION: This literature review offers
      researchers and clinicians a list of sexual distress measures and relevant
      characteristics that can be used to select the best assessment tool for their
      objectives. STRENGTHS AND LIMITATIONS: A thorough search procedure was used;
      however, there is still a chance that relevant articles might have been missed
      owing to our search methodology and inclusion criteria. CONCLUSION: This is a
      novel and state-of-the-art review of assessment tools for sexual distress that
      includes valuable information measure selection in the study of sexual distress
      and sexual dysfunction. Santos-Iglesias P, Mohamed B, Walker LM. A Systematic
      Review of Sexual Distress Measures. J Sex Med 2018;15:625-644.

PMID- 29576432
TI  - Reply to "Therapeutic management of people with epilepsy in low- and middle
      income countries".

PMID- 29576433
TI  - Cognitive and clinical variables associated with interictal dysphoric disorder in
      patients with epilepsy.
AB  - PURPOSE: The relationship between interictal dysphoric disorder (IDD) and
      cognitive impairment in adult patients with epilepsy (PWE) is poorly studied.
      METHODS: The Interictal Dysphoric Disorder Inventory (IDDI) with cognitive and
      clinical aspects was compared with Quality of Life in Epilepsy Inventory (QOLIE
      31) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scores
      of 117 PWE at significance level p<0.05. RESULTS: Interictal dysphoric disorder
      occurred in 25 (21.4%) PWE, and it was significantly associated with the presence
      of psychiatric disorders (PD) (alpha2; p=0.007), presence of major depressive
      episodes (p=0.03), lower educational level, older individuals, and those with a
      lower performance in the category fluency test (VF) (9.7+/-5.1 vs. 12.2+/-4.2; t
      test; p=0.037). There was a negative correlation between QOLIE-31 and IDD. The
      predictive factors for the occurrence of IDD were the presence of PD (p=0.014)
      and lower performance in the VF (p=0.013). CONCLUSION: The occurrence of IDD was
      high. Interictal dysphoric disorder was found in different epileptic syndromes,
      and it was associated with the presence of PD, depressive episodes, lower
      performance in VF, and lower quality of life (QoL).

PMID- 29576434
TI  - Surgical versus medical treatment of drug-resistant epilepsy: A systematic review
      and meta-analysis.
AB  - OBJECTIVE: Surgery and drug therapy are the two main treatments for refractory
      epilepsy. However, to date, there has not been an adequate comparison of the
      outcomes of these two treatments. This systematic review compared the overall
      outcome of surgery and medical treatment in patients with drug-resistant
      epilepsy. METHODS: Articles published in Embase, Medline, Pubmed, and the
      Cochrane library were searched from their inception until June 2016. RESULTS:
      Twenty of the eighty-one (24.7%) full-text articles reviewed fulfilled the
      eligibility criteria and were included in the meta-analysis. Of 1800 patients
      with drug-resistant epilepsy, 526 of 923 patients (57.0%) in the surgery group
      were seizure-free compared with 134 of 877 patients (15.3%) in the medical
      treatment group (19 studies, risk ratio (RR)=3.72, 95% confidence interval (CI)
      [2.75-5.03]; P<0.00001, I2=53%). In addition, more patients were off
      antiepileptic drugs (AEDs) in the surgical group (3 studies, n=438, RR=4.76, 95%
      CI [2.21, 10.28], P<0.0001, I2=0%). Although different studies used different
      questionnaires to assess patient quality of life (QOL) in both treatment groups,
      the overall postintervention QOL scores were higher in the surgery than in the
      medical treatment group, by SMD (6 studies, n=459, SMD=0.61, 95% CI [0.23, 0.98],
      P=0.002, I2=66%). CONCLUSION: As the complications of interventions, declines in
      memory, and word recall/naming were not assessed in the meta-analysis, the
      conclusions are limited to seizure-free, AED use, and QOL. The current evidence
      indicate that compared with medical treatment, surgery is more likely to achieve
      seizure-free, off AEDs, and better QOL.

PMID- 29576435
TI  - Adults with an epilepsy history, especially those 45years or older, those with
      lower family incomes, and those with a history of hypertension, report a history
      of stroke five times as often as adults without such a history-2010, 2013, and
      2015 U.S. National Health Interview Survey.

PMID- 29576436
TI  - Electrocorticographic high-gamma language mapping: Limitations of comparisons
      with electrocortical stimulation.

PMID- 29576438
TI  - Light disturbance with multifocal contact lens and monovision for presbyopia.
AB  - : Dysphotopsia affects a significant number of patients, particularly after
      visual correction with multifocal optical designs. PURPOSE: Evaluate light
      distortion (LD) in two modalities of contact lens (CL) wear: multifocal (MF) and
      monofocal (MV). METHODS: This was a randomized, double-masked, crossover study
      involving 20 presbyopic patients. Patients were randomized first into either MF
      or MV for 15 days of use with a 1 week wash-out period between each lens type.
      The LD was evaluated with the Light Distortion Analyzer (LDA, University of
      Minho) under monocular and binocular conditions. The light distortion index (LDI,
      %), among other parameters were analyzed. Subjective quality of vision was
      assessed with the Quality of Vision (QoV). RESULTS: The LD showed an increase in
      all parameters in both CL modalities being significant for MV in the non-dominant
      eye (p < 0.030, for all LD parameters). For the MF, there was also a significant
      increase in LDI (p = 0.016) and in BFCrad (p = 0.022) in the non-dominant eye.
      After 15 days of MF lens wear, there was a significant decrease in all LD
      parameters (p < 0.002) in the dominant eye. Binocularly, a significant
      improvement from 1 to 15 days was observed for LDI (p = 0.009) and BFCrad (p =
      0.0013) with MF. The QoV questionnaire showed no significant changes with neither
      CL. CONCLUSIONS: Adaptation to light disturbances induced by MF CL is more
      effective compared to MV. Practitioners will have greater success if they prepare
      their patients for the adaptation required as their vision will get better and
      have less of an issue with light disturbance.

PMID- 29576437
TI  - Enterochromaffin 5-HT cells - A major target for GLP-1 and gut microbial
      metabolites.
AB  - OBJECTIVES: 5-HT storing enterochromaffin (EC) cells are believed to respond to
      nutrient and gut microbial components, and 5-HT receptor-expressing afferent
      vagal neurons have been described to be the major sensors of nutrients in the GI
      tract. However, the molecular mechanism through which EC cells sense nutrients
      and gut microbiota is still unclear. METHODS AND RESULTS: TPH1, the 5-HT
      generating enzyme, and chromogranin A, an acidic protein responsible for
      secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells
      from both small intestine and colon using a 5-HT antibody-based method.
      Surprisingly, EC cells from the small intestine did not express GPCR sensors for
      lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1 (TGR5), CaSR, and
      GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell.
      However, the GLP-1 receptor was particularly highly expressed and enriched in EC
      cells as judged both by qPCR and by immunohistochemistry using a receptor
      antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from
      intestinal preparations using both HPLC and a specific amperometric method.
      Colonic EC cells expressed many different types of known and potential GPCR
      sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2,
      OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids
      GPBAR1; and acyl-amides and lactate, GPR132. CONCLUSION: Nutrient metabolites
      apparently do not stimulate EC cells of the small intestine directly but through
      a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine
      cells. In contrast, colonic EC cells are able to sense a multitude of different
      metabolites generated by the gut microbiota as well as gut hormones, including
      GLP-1.

PMID- 29576439
TI  - LRRK2 protective haplotype and full sequencing study in REM sleep behavior
      disorder.
AB  - BACKGROUND: Individuals with rapid eye movement (REM)-sleep behavior disorder
      (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease
      (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The
      genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2
      variants in risk for RBD is still not clear. METHODS: The full coding sequence,
      exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced
      using targeted next-generation sequencing. A total of 350 RBD patients and 869
      controls were sequenced, and regression and burden models were used to examine
      the association between LRRK2 variants and RBD. RESULTS: No pathogenic mutations
      that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H
      p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI
      0.44-0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant,
      p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% CI 1.05
      1.56, p = 0.029). Burden analysis identified associations with domains and exons
      that were derived by the variants of the protective haplotype, and no burden of
      other rare variants was identified. CONCLUSIONS: Carriers of the LRRK2 p.N551K
      p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD
      causing mutations probably have minor or no role in RBD. Additional work is
      needed to confirm these results and to identify the mechanism associated with
      reduced risk for RBD.

PMID- 29576440
TI  - Evolution of dietary preferences and the innate urge to heal: Drug discovery
      lessons from Ayurveda.
AB  - Highly specialized and functionally integrated cognitive systems facilitate
      hedonistic and healthy food preferences. Guided by survival needs, flavor
      preferences not only select safe, nutritious dietary components, but also those
      with negligible calorific value but significant health benefits, for example,
      spices. Feeding behavior, both innate and acquired, is guided not only by taste
      receptors on the tongue but also visceral organs. The gustatory cortex receives
      information from all senses, not just taste, suggesting multiple checkpoints in
      predicting and evaluating healthy foods. Ayurvedic interpretation of 'rasa' as
      chemistry is compatible with medicinal value of diets because, taste and odor are
      chemosensory perceptions. As flavor and taste are linked to the chemical
      structure of compounds, taste might offer clues about pharmacological activity.
      Ayurvedic idea of vipaka, or post digestive perception of taste, recognizes the
      extended role of taste receptors beyond the tongue and stretching into the
      viscera. Ayurvedic wisdom is consistent with evolutionary guideposts that suggest
      three successive stages of nutritional appraisal: before, during, and after
      ingesting food. While olfaction induces affinity or revulsion even before
      ingestion, gustatory receptors on the tongue evaluates nutritional value upon
      contact, and the chemoreceptors in the deeper metabolic systems probably
      pronounce the final verdict on the nutritive and health benefits of ingested
      substances. Alliesthesia, neophobia, and the extreme variation in human T2R genes
      (coding for bitterness receptors) illustrate the importance of adaptive learning
      of dietary preferences. These evolutionary clues are compatible with the
      Ayurvedic principle of 'rasa', in facilitating the process of drug discovery.

PMID- 29576441
TI  - Low-Intensity Shockwave Therapy for Erectile Dysfunction.
AB  - BACKGROUND: Vasculogenic erectile dysfunction (ED) is one of the leading causes
      of male sexual dysfunction. In the past decade, multiple studies have examined
      the use of low-intensity extracorporeal shockwave therapy (Li-ESWT) for the
      treatment of ED. AIM: Investigate the efficacy of Li-ESWT for the treatment of
      ED. METHODS: We reviewed the published literature, including randomized
      controlled trials (RCTs), meta-analyses, and select single-arm studies on the use
      of Li-ESWT for the treatment of ED. OUTCOMES: Changes in International Index of
      Erectile Function scores were evaluated in patients undergoing Li-ESWT. RESULTS:
      There is no consensus from RCTs on the efficacy of Li-ESWT for the treatment of
      ED. Published meta-analyses have shown significant improvement in International
      Index of Erectile Function-erectile function domain scores in men undergoing Li
      ESWT, especially when compared to men receiving sham treatment. However,
      differences in treatment protocols limit the generalizability of these findings.
      Li-ESWT may be more beneficial in cases of mild ED or when combined with
      phosphodiesterase type 5 inhibitors in men with moderate to severe ED. The role
      of Li-ESWT in the treatment of non-vasculogenic ED remains poorly defined.
      CONCLUSIONS: Li-ESWT could be beneficial in specific sub-sets of men with
      vasculogenic ED. However, future RCTs should attempt to optimize treatment
      protocols and have more stringent inclusion criteria to confirm these findings.
      Rizk PJ, Krieger JR, Kohn TP, et al. Low-Intensity Shockwave Therapy for Erectile
      Dysfunction. Sex Med Rev 2018;6:624-630.

PMID- 29576443
TI  - Modifiable risk factors for acute skin toxicity in adjuvant breast radiotherapy:
      Dosimetric analysis and review of the literature.
AB  - Acute skin toxicity in adjuvant breast radiation can be reduced with modern
      radiotherapy (RT) techniques. However, having reviewed the literature, we found
      no dosimetric constraint for acute skin toxicity that would be applicable to
      modern RT planning. This study aimed to identify dosimetric factors that are
      associated with higher rates of acute skin toxicity. A retrospective review was
      carried out including women who received adjuvant forward-planned intensity
      modulated radiotherapy (IMRT) after breast-conserving surgery. Acute skin
      toxicity grade was prospectively recorded. A total of 131 patients were analyzed.
      On multivariate analysis, the V105% > 30 cc (p = 0.013) and the use of
      conventional fractionation (CF) (p = 0.001) were statistically significant for
      acute skin toxicity. On literature review, current quantitative dosimetric
      parameters that have shown statistical significance include a V107% > 3 cc in
      hypofractionation (HF), V107% > 9 cc in CF, treated volume 110% > 5.13%, and
      V107% > 28.6%. There is little evidence on the predictive value of clinically
      applicable dosimetric factors in acute skin toxicity. Given the recent
      improvements in RT planning, we would consider a V107% or a V110% too high a
      dosimetric value to be useful for the majority of patients. We have shown that a
      V105% of greater than 30 cc is significantly associated with acute skin toxicity,
      controlling for other variables. We suggest that this is currently the most
      useful modifiable parameter available to reduce skin toxicity and is applicable
      to modern RT planning. We also suggest that consideration be given to
      hypofractionated schedules to further reduce acute skin toxicity.

PMID- 29576442
TI  - Effect Size in Efficacy Trials of Women With Decreased Sexual Desire.
AB  - BACKGROUND: Regarding hypoactive sexual desire disorder (HSDD) in women, some
      reviewers judge the effect size small for medications vs placebo, but substantial
      for cognitive behavior therapy (CBT) or mindfulness meditation training (MMT) vs
      wait list. However, we lack comparisons of the effect sizes for the active
      intervention itself, for the control treatment, and for the differential between
      the two. AIM: For efficacy trials of HSDD in women, compare effect sizes for
      medications (testosterone/testosterone transdermal system, flibanserin, and
      bremelanotide) and placebo vs effect sizes for psychotherapy and wait-list
      control. METHODS: We conducted a literature search for mean changes and SD on
      main measures of sexual desire and associated distress in trials of medications,
      CBT, or MMT. Effect size was used as it measures the magnitude of the
      intervention without confounding by sample size. OUTCOMES: Cohen d was used to
      determine effect sizes. RESULTS: For medications, mean (SD) effect size was 1.0
      (0.34); for CBT and MMT, 1.0 (0.36); for placebo, 0.55 (0.16); and for wait list,
      0.05 (0.26). CLINICAL TRANSLATION: Recommendations of psychotherapy over
      medication for treatment of HSDD are premature and not supported by data on
      effect sizes. Active participation in treatment conveys considerable non-specific
      benefits. Caregivers should attend to biological and psychosocial elements, and
      patient preference, to optimize response. CONCLUSIONS: Few clinical trials of
      psychotherapies were substantial in size or utilized adequate control paradigms.
      Medications and psychotherapies had similar, large effect sizes. Effect size of
      placebo was moderate. Effect size of wait-list control was very small, about one
      quarter that of placebo. Thus, a substantial non-specific therapeutic effect is
      associated with receiving placebo plus active care and evaluation. The difference
      in effect size between placebo and wait-list controls distorts the value of the
      subtraction of effect of the control paradigms to estimate intervention
      effectiveness. Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With
      Decreased Sexual Desire. Sex Med Rev 2018;6:358-366.

PMID- 29576444
TI  - Biparametric Prostate Imaging Reporting and Data System version2 and
      International Society of Urological Pathology Grade Predict Biochemical
      Recurrence after Radical Prostatectomy.
AB  - BACKGROUND: We retrospectively assessed the clinical significance of the Prostate
      Imaging Reporting and Data System (PI-RADS), version 2, criteria based on
      biparametric magnetic resonance imaging (bp-MRI), together with the International
      Society of Urological Pathology (ISUP) grade, for predicting biochemical
      recurrence (BCR) after radical prostatectomy. MATERIALS AND METHODS: The data
      from 126 patients who had undergone radical prostatectomy were retrospectively
      analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was
      assessed with other clinical factors, including the ISUP grade. We defined a
      positive PI-RADS and ISUP score as >= 4 and >= 3, respectively. Statistical
      analysis was performed using Cox proportional hazard models, logistic regression
      analysis, and the Kaplan-Meier method. RESULTS: The median age and median
      prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The
      number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP
      grade scores was 71 (56.3%). PI-RADS >= 4 (P = .0031) and ISUP >= 3 (P = .070)
      were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS
      score was related to tumor volume (P = .014), and a positive ISUP score was
      related to prostate-specific antigen level (P = .043), extraprostatic extension
      (P = .029), and Gleason upgrading (P < .0001). After stratifying patients into
      risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI
      RADS and ISUP grade positive) showed significantly worse BCR-free survival
      compared with that of the favorable- and intermediate-risk groups (P < .0001),
      with a median survival difference of 21 months. CONCLUSION: Biparametric PI-RADS
      v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS
      v2 combined with the ISUP grade might be helpful in choosing the treatment
      modality of patients with localized prostate cancer.

PMID- 29576445
TI  - Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive
      Bladder Cancer Patients With Diminished Renal Function.
AB  - BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) before radical
      cystectomy is the standard of care in muscle-invasive bladder cancer. There are
      limited data regarding chemotherapy tolerability and outcomes for patients with
      low glomerular filtration rate (GFR) who receive cisplatin-based NAC. PATIENTS
      AND METHODS: A retrospective analysis of patients who received cisplatin-based
      NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR <
      60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease
      (MDRD) formula were compared to patients with GFR >= 60 mL/min for NAC
      tolerability, pathologic complete and partial response (pPR), and the ability to
      undergo radical cystectomy. RESULTS: Thirty patients with low GFR (34-59 mL/min)
      and 94 patients with normal GFR (>= 60 mL/min) were identified. Low GFR patients
      were older (median, 71 vs. 65 years), but other demographic and transurethral
      resection of bladder tumor characteristics were comparable. Low GFR patients more
      frequently had early NAC discontinuation (30% vs. 13%), NAC modifications
      (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based
      NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability
      or outcomes were noted among low GFR patients receiving split-dose versus
      standard regimens. No differences were noted between low and normal GFR patients
      in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to
      cystectomy, and GFR change from baseline to after NAC. Pathologic complete
      response was higher among normal GFR patients (24% vs. 14%). CONCLUSION: Patients
      with low GFR had more NAC discontinuations and modifications, but most completed
      planned NAC cycles. For carefully selected patients with GFR < 60 mL/min,
      cisplatin-based NAC remains a treatment option.

PMID- 29576446
TI  - Online Sales of Marijuana: An Unrecognized Public Health Dilemma.

PMID- 29576447
TI  - [Telephone support for breastfeeding by primary care: a randomised multicentre
      trial].
AB  - OBJECTIVE: To evaluate a telephone support programme for mothers who breastfeed
      for the first 6 months. METHODS: A randomised unmasked clinical trial was
      conducted in 5 urban Primary Care centres that included mothers with healthy
      newborns who were breastfeeding exclusively (EBF) or partially (PBF). The control
      group received the usual care. The intervention group also received telephone
      support for breastfeeding on a weekly basis for the first 2months and then every
      2weeks until the sixth month. The type of breastfeeding was recorded in the usual
      check-up visit (1, 2, 4 and 6 months). RESULTS: The study included 193 patients
      in the intervention group, and 187 in a control group. The greatest increase in
      the percentage of EBF was observed at 6 months: 21.4% in the control group
      compared to 30.1% in the intervention group. However, in the adjusted odds ratios
      analysis, confidence intervals did not show statistical significance. The odds
      ratio at 1 month, 2 months, 4 months, and 6 months for EBF were 1.45 (0.91-2.31),
      1.35 (0.87-2.08), 1.21 (0.80-1.81), and 1.58 (0.99-2.53), respectively. The odds
      ratio in the same age groups for any type of breastfeeding (EBF + PBF) were 1.65
      (0.39-7.00), 2.08 (0.94-4.61), 1.37 (0.79-2.38), and 1.60 (0.98-2.61),
      respectively. CONCLUSIONS: Telephone intervention was not effective enough to
      generalise it.

PMID- 29576448
TI  - Dual inhibition of PI3K/mTOR signaling in chemoresistant AML primary cells.
AB  - A main cause of treatment failure for AML patients is resistance to chemotherapy.
      Survival of AML cells may depend on mechanisms that elude conventional drugs
      action and/or on the presence of leukemia initiating cells at diagnosis, and
      their persistence after therapy. MDR1 gene is an ATP-dependent drug efflux pump
      known to be a risk factor for the emergence of resistance, when combined to
      unstable cytogenetic profile of AML patients. In the present study, we analyzed
      the sensitivity to conventional chemotherapeutic drugs of 26 samples of primary
      blasts collected from AML patients at diagnosis. Detection of cell viability and
      apoptosis allowed to identify two group of samples, one resistant and one
      sensitive to in vitro treatment. The cells were then analyzed for the presence
      and the activity of P-glycoprotein. A comparative analysis showed that resistant
      samples exhibited a high level of MDR1 mRNA as well as of P-glycoprotein content
      and activity. Moreover, they also displayed high PI3K signaling. Therefore, we
      checked whether the association with signaling inhibitors might resensitize
      resistant samples to chemo-drugs. The combination showed a very potent cytotoxic
      effect, possibly through down modulation of MDR1, which was maintained also when
      primary blasts were co-cultured with human stromal cells. Remarkably, dual
      PI3K/mTOR inactivation was cytotoxic also to leukemia initiating cells. All
      together, our findings indicate that signaling activation profiling associated to
      gene expression can be very useful to stratify patients and improve therapy.

PMID- 29576449
TI  - Expanding Actin Rings Zipper the Mouse Embryo for Blastocyst Formation.
AB  - Transformation from morula to blastocyst is a defining event of preimplantation
      embryo development. During this transition, the embryo must establish a
      paracellular permeability barrier to enable expansion of the blastocyst cavity.
      Here, using live imaging of mouse embryos, we reveal an actin-zippering mechanism
      driving this embryo sealing. Preceding blastocyst stage, a cortical F-actin ring
      assembles at the apical pole of the embryo's outer cells. The ring structure
      forms when cortical actin flows encounter a network of polar microtubules that
      exclude F-actin. Unlike stereotypical actin rings, the actin rings of the mouse
      embryo are not contractile, but instead, they expand to the cell-cell junctions.
      Here, they couple to the junctions by recruiting and stabilizing adherens and
      tight junction components. Coupling of the actin rings triggers localized myosin
      II accumulation, and it initiates a tension-dependent zippering mechanism along
      the junctions that is required to seal the embryo for blastocyst formation.

PMID- 29576450
TI  - Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates
      Plasmodium Infection.
AB  - Hereditary xerocytosis is thought to be a rare genetic condition characterized by
      red blood cell (RBC) dehydration with mild hemolysis. RBC dehydration is linked
      to reduced Plasmodium infection in vitro; however, the role of RBC dehydration in
      protection against malaria in vivo is unknown. Most cases of hereditary
      xerocytosis are associated with gain-of-function mutations in PIEZO1, a
      mechanically activated ion channel. We engineered a mouse model of hereditary
      xerocytosis and show that Plasmodium infection fails to cause experimental
      cerebral malaria in these mice due to the action of Piezo1 in RBCs and in T
      cells. Remarkably, we identified a novel human gain-of-function PIEZO1 allele,
      E756del, present in a third of the African population. RBCs from individuals
      carrying this allele are dehydrated and display reduced Plasmodium infection in
      vitro. The existence of a gain-of-function PIEZO1 at such high frequencies is
      surprising and suggests an association with malaria resistance.

PMID- 29576451
TI  - IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation.
AB  - Inflammasome activation is critical for host defenses against various microbial
      infections. Activation of the NLRC4 inflammasome requires detection of flagellin
      or type III secretion system (T3SS) components by NLR family apoptosis inhibitory
      proteins (NAIPs); yet how this pathway is regulated is unknown. Here, we found
      that interferon regulatory factor 8 (IRF8) is required for optimal activation of
      the NLRC4 inflammasome in bone-marrow-derived macrophages infected with
      Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but
      is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and
      Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection
      of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation.
      Furthermore, we found that IRF8 confers protection against bacterial infection in
      vivo, owing to its role in inflammasome-dependent cytokine production and
      pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of
      NAIPs and NLRC4 inflammasome activation for defense against bacterial infection.

PMID- 29576453
TI  - Flavin Monooxygenase-Generated N-Hydroxypipecolic Acid Is a Critical Element of
      Plant Systemic Immunity.
AB  - Following a previous microbial inoculation, plants can induce broad-spectrum
      immunity to pathogen infection, a phenomenon known as systemic acquired
      resistance (SAR). SAR establishment in Arabidopsis thaliana is regulated by the
      Lys catabolite pipecolic acid (Pip) and flavin-dependent-monooxygenase1 (FMO1).
      Here, we show that elevated Pip is sufficient to induce an FMO1-dependent
      transcriptional reprogramming of leaves that is reminiscent of SAR. In planta and
      in vitro analyses demonstrate that FMO1 functions as a pipecolate N-hydroxylase,
      catalyzing the biochemical conversion of Pip to N-hydroxypipecolic acid (NHP).
      NHP systemically accumulates in plants after microbial attack. When exogenously
      applied, it overrides the defect of NHP-deficient fmo1 in acquired resistance and
      acts as a potent inducer of plant immunity to bacterial and oomycete infection.
      Our work has identified a pathogen-inducible L-Lys catabolic pathway in plants
      that generates the N-hydroxylated amino acid NHP as a critical regulator of
      systemic acquired resistance to pathogen infection.

PMID- 29576454
TI  - Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and
      Aneuploidy Patterns.
AB  - Genomics has provided a detailed structural description of the cancer genome.
      Identifying oncogenic drivers that work primarily through dosage changes is a
      current challenge. Unrestrained proliferation is a critical hallmark of cancer.
      We constructed modular, barcoded libraries of human open reading frames (ORFs)
      and performed screens for proliferation regulators in multiple cell types.
      Approximately 10% of genes regulate proliferation, with most performing in an
      unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell
      type showed specific enrichment in somatic copy number changes (SCNAs) from
      cognate tumors and helped predict aneuploidy patterns in those tumors, implying
      that tissue-type-specific genetic network architectures underlie SCNA and driver
      selection in different cancers. In vivo screening confirmed these results. We
      report a substantial contribution to the catalog of SCNA-associated cancer
      drivers, identifying 147 amplified and 107 deleted genes as potential drivers,
      and derive insights about the genetic network architecture of aneuploidy in
      tumors.

PMID- 29576452
TI  - iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its
      Potential Medical Applications.
AB  - Hibernating mammals survive hypothermia (<10 degrees C) without injury, a
      remarkable feat of cellular preservation that bears significance for potential
      medical applications. However, mechanisms imparting cold resistance, such as
      cytoskeleton stability, remain elusive. Using the first iPSC line from a
      hibernating mammal (13-lined ground squirrel), we uncovered cellular pathways
      critical for cold tolerance. Comparison between human and ground squirrel iPSC
      derived neurons revealed differential mitochondrial and protein quality control
      responses to cold. In human iPSC-neurons, cold triggered mitochondrial stress,
      resulting in reactive oxygen species overproduction and lysosomal membrane
      permeabilization, contributing to microtubule destruction. Manipulations of these
      pathways endowed microtubule cold stability upon human iPSC-neurons and rat (a
      non-hibernator) retina, preserving its light responsiveness after prolonged cold
      exposure. Furthermore, these treatments significantly improved microtubule
      integrity in cold-stored kidneys, demonstrating the potential for prolonging
      shelf-life of organ transplants. Thus, ground squirrel iPSCs offer a unique
      platform for bringing cold-adaptive strategies from hibernators to humans in
      clinical applications. VIDEO ABSTRACT.

PMID- 29576455
TI  - Development of Concurrent Retinotopic Maps in the Fly Motion Detection Circuit.
AB  - Understanding how complex brain wiring is produced during development is a
      daunting challenge. In Drosophila, information from 800 retinal ommatidia is
      processed in distinct brain neuropiles, each subdivided into 800 matching
      retinotopic columns. The lobula plate comprises four T4 and four T5 neuronal
      subtypes. T4 neurons respond to bright edge motion, whereas T5 neurons respond to
      dark edge motion. Each is tuned to motion in one of the four cardinal directions,
      effectively establishing eight concurrent retinotopic maps to support wide-field
      motion. We discovered a mode of neurogenesis where two sequential Notch-dependent
      divisions of either a horizontal or a vertical progenitor produce matching sets
      of two T4 and two T5 neurons retinotopically coincident with pairwise opposite
      direction selectivity. We show that retinotopy is an emergent characteristic of
      this neurogenic program and derives directly from neuronal birth order. Our work
      illustrates how simple developmental rules can implement complex neural
      organization.

PMID- 29576457
TI  - The effect of template-based sequential (TBS) coding on an NHS plastic surgical
      practice.
AB  - INTRODUCTION: Clinical coding is often a mystery to us surgeons, but in
      actuality, it has a huge bearing on the financial sustainability of our services.
      Given the rapid innovations in plastic surgical procedures, clinical coders often
      struggle to decipher the extent of surgery. Meeting midway is the way forward
      here. METHODS: In a prospective audit over a six-month period, we analysed data
      from 2586 patients in our practice: a combination of general plastic surgery and
      specialist facial reanimation services. This involved comparing data from the
      first three months where coding was performed by clinical coders based on
      operating notes per se (phase I) and the subsequent three months when the
      operating surgeon filled in the OPCS 4.7 (version 2014) codes at the time of
      completing the operating notes; the clinical coders then vetted this information
      (phase II) as part of a sequential TBS coding system. RESULTS: In terms of
      outpatient income, there was a 3% increase in facial palsy income and 6% increase
      in general plastic services, but the most significant improvement was in terms of
      procedural income per case. General plastic surgery cases saw an increase of 49%,
      while facial palsy income increased by 58% over the same period. Greater insight
      into OPCS and HRG codes also allowed for the calculation of the actual tariffs
      for specific procedures. CONCLUSIONS: Having the operating surgeon as the primary
      coder, using a template, with subsequent vetting by the clinical coders, improves
      data capture, and this in turn increases income. Future recommendations include
      the use of proforma-based operating notes for workhorse procedures.

PMID- 29576456
TI  - Phase Transitions in the Assembly and Function of Human miRISC.
AB  - miRISC is a multi-protein assembly that uses microRNAs (miRNAs) to identify mRNAs
      targeted for repression. Dozens of miRISC-associated proteins have been
      identified, and interactions between many factors have been examined in detail.
      However, the physical nature of the complex remains unknown. Here, we show that
      two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B,
      condense into phase-separated droplets in vitro and in live cells. Phase
      separation is promoted by multivalent interactions between the glycine/tryptophan
      (GW)-rich domain of TNRC6B and three evenly spaced tryptophan-binding pockets in
      the Ago2 PIWI domain. miRISC droplets formed in vitro recruit deadenylation
      factors and sequester target RNAs from the bulk solution. The condensation of
      miRISC is accompanied by accelerated deadenylation of target RNAs bound to Ago2.
      The combined results may explain how miRISC silences mRNAs of varying size and
      structure and provide experimental evidence that protein-mediated phase
      separation can facilitate an RNA processing reaction.

PMID- 29576458
TI  - Encapsulation of mesenchymal stem cells in chitosan/beta-glycerophosphate
      hydrogel for seeding on a novel calcium phosphate cement scaffold.
AB  - Due to its moldability, biocompatibility, osteoconductivity and resorbability,
      calcium phosphate cement (CPC) is a highly promising scaffold material for
      orthopedic applications. However, pH changes and ionic activity during the CPC
      setting reaction may adversely affect cells seeded directly on CPC. Moreover, a
      lack of macropores in CPC limits ingrowth of new bone. The objectives of this
      study were to prepare macroporous CPC scaffolds via porogen leaching, using
      mannitol crystals as the porogen and to evaluate the in vitro proliferation and
      osteogenic differentiation of mesenchymal stem cells (MSCs) encapsulated in
      chitosan/beta-glycerophosphate (C/GP) hydrogel prior to exposure to the novel CPC
      scaffold. MSCs were found to be adhered to the surfaces of CPC macropores via
      scanning electron microscopy. The viability and osteogenic differentiation of
      MSCs in C/GP hydrogel with or without exposure to CPC constructs containing
      mannitol crystals indicated that coating with C/GP hydrogel protected the cells
      during cement mixing and setting. In conclusion, novel, macroporous CPC scaffolds
      were prepared, and our data indicate that a hydrogel encapsulation-based strategy
      can be used to protect cells during scaffold formation. Thus, the MSC-laden CPC
      scaffolds show promise for the delivery of stem cells to promote bone
      regeneration.

PMID- 29576459
TI  - Simple and efficient thermal calibration for MEMS gyroscopes.
AB  - Gyroscopes are now becoming one of the most sold MEMS sensors, given that the
      many applications that require their use are booming. In the medical field,
      gyroscopes can be found in Inertial Measurement Units used for the development of
      clinical tools that are dedicated to human-movement monitoring. However, MEMS
      gyroscopes are known to suffer from a drift phenomenon, which is mainly due to
      temperature variations. This drift dramatically affects measurement capability,
      especially that of cheap MEMs gyroscopes. Calibration is therefore a key factor
      in achieving accurate measurements. However, traditional calibration procedures
      are often complex and require costly equipment. This paper therefore proposes an
      easy protocol for performing a thermal gyroscope calibration. In this protocol,
      accuracy over the angular velocity is evaluated by referring to an optoelectronic
      measurement, and is compared with the traditional calibration performed by the
      manufacturer. The RMSE between the reference angular velocity and that obtained
      with the proposed calibration was of 0.7 degrees /s, which was slightly smaller
      than the RMSE of 1.1 degrees /s achieved by the manufacturer's calibration. An
      analysis of uncertainty propagation shows that offset variability is the major
      source of error over the computed rate of rotation from the tested sensors, since
      it accounts for 97% of the error. It can be concluded that the proposed simple
      calibration method leads to a similar degree of accuracy as that achieved by the
      manufacturer's procedure.

PMID- 29576460
TI  - Shape-memory-alloy-based smart knee spacer for total knee arthroplasty: 3D CAD
      modelling and a computational study.
AB  - This study introduced a shape memory alloy (SMA)-based smart knee spacer for
      total knee arthroplasty (TKA). Subsequently, a 3D CAD model of a smart tibial
      component of TKA was designed in Solidworks software, and verified using a finite
      element analysis in ANSYS Workbench. The two major properties of the SMA (NiTi),
      the pseudoelasticity (PE) and shape memory effect (SME), were exploited,
      modelled, and analysed for a TKA application. The effectiveness of the proposed
      model was verified in ANSYS Workbench through the finite element analysis (FEA)
      of the maximum deformation and equivalent (von Mises) stress distribution. The
      proposed model was also compared with a polymethylmethacrylate (PMMA)-based
      spacer for the upper portion of the tibial component for three subjects with body
      mass index (BMI) of 23.88, 31.09, and 38.39. The proposed SMA -based smart knee
      spacer contained 96.66978% less deformation with a standard deviation of 0.01738
      than that of the corresponding PMMA based counterpart for the same load and
      flexion angle. Based on the maximum deformation analysis, the PMMA-based spacer
      had 30 times more permanent deformation than that of the proposed SMA-based
      spacer for the same load and flexion angle. The SME property of the lower portion
      of the tibial component for fixation of the spacer at its position was verified
      by an FEA in ANSYS. Wherein, a strain life-based fatigue analysis was performed
      and tested for the PE and SME built spacers through the FEA. Therefore, the SMA
      based smart knee spacer eliminated the drawbacks of the PMMA-based spacer,
      including spacer fracture, loosening, dislocation, tilting or translation, and
      knee subluxation.

PMID- 29576461
TI  - A patient specific finite element simulation of intramedullary nailing to predict
      the displacement of the distal locking hole.
AB  - Distal locking is a challenging subtask of intramedullary nailing fracture
      fixation due to the nail deformation that makes the proximally mounted targeting
      systems ineffective. A patient specific finite element model was developed, based
      on the QCT data of a cadaveric femur, to predict the position of the distal hole
      of the nail postoperatively. The mechanical interactions of femur and nail (of
      two sizes) during nail insertion was simulated using ABAQUS in two steps of
      dynamic pushing and static equilibrium, for the intact and distally fractured
      bone. Experiments were also performed on the same specimen to validate the
      simulation results. A good agreement was found between the model predictions and
      the experimental observations. There was a three-point contact pattern between
      the nail and medullary canal, only on the proximal fragment of the fractured
      bone. The nail deflection was much larger in the sagittal plane and increased for
      the larger diameter nail, as well as for more distally fractured or intact femur.
      The altered position of the distal hole was predicted by the model with an
      acceptable error (mean: 0.95; max: 1.5 mm, in different tests) to be used as the
      compensatory information for fine tuning of proximally mounted targeting systems.

PMID- 29576462
TI  - Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of
      the ovary: Results from the MITO-9 study.
AB  - OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type
      granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent
      course of the disease, no prospective trials are available. Open surgery has long
      been considered the traditional approach; oncological safety of laparoscopy is
      only supported by small series or case reports. The aim of this study was to
      compare the oncological outcomes between laparoscopic and open surgery in stage I
      AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer)
      Group. METHODS: Data from patients with stage I AGCTs were retrospectively
      collected. Clinicopathological features were evaluated for association with
      relapse and death. Survival curves were calculated using the Kaplan-Meier method
      and compared with the log-rank test. The role of clinicopathological variables as
      prognostic factors for survival was evaluated using Cox's regression model.
      RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and
      29.6% respectively. 7.6% were apparently stage I. Surgical approach was
      laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was
      84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p
      = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the
      laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC,
      incomplete staging, site of primary surgery retained significant prognostic
      value. CONCLUSION: The present study suggests that surgical route does not affect
      the oncological safety of patients with stage I AGCTs, with comparable outcomes
      between laparoscopic and open approach.

PMID- 29576463
TI  - Risk factors for appendiceal and colorectal peritoneal metastases.
AB  - BACKGROUND: Early diagnosis to target minimal volume disease has received
      increased attention in the management of appendiceal and colorectal peritoneal
      metastases (PM). This study aimed to identify risk factors for appendiceal, colon
      and rectal PM. METHODS: Data were retrieved from the Swedish Colorectal Cancer
      Registry for all patients undergoing bowel resection of appendiceal and
      colorectal tumours, in Sweden, 2007-2015. Risk factors for synchronous and
      metachronous PM were analysed with multivariate logistic and Cox proportional
      hazard regression models. RESULTS: Synchronous PM was most common in appendiceal
      cancer (23.5%), followed by colon (3.1%) and rectal (0.6%) cancer. The 5-year
      cumulative incidence was 9.0% for appendiceal, 2.5% for right colon, 1.8% for
      left colon and 1.2% for rectal cancer. In appendiceal cancer (n = 327), T4, N2,
      mucinous tumour, and non-radical surgery were associated with PM. In colon cancer
      (n = 24,399), synchronous PM were primarily associated with T4 (OR 18.37, 95% CI
      8.12-41.53), T3 and N2 but also with N1, right-sided tumour, mucinous tumour,
      vascular and perineural invasion, female gender, age <60 and emergency surgery.
      These factors were also associated with metachronous PM. In rectal cancer (n =
      10,394), T4 (OR 19.12, 95% CI 5.52-66.24), proximal tumour and mucinous tumour
      were associated with synchronous PM and T4 and mucinous tumour with metachronous
      PM. CONCLUSIONS: This study shows that appendiceal cancer, right-sided colon
      cancer, advanced tumour and node stages and mucinous histopathology are the main
      high-risk features for PM and should increase the awareness of current or future
      PM.

PMID- 29576464
TI  - Normalization and the Cholinergic Microcircuit: A Unified Basis for Attention.
AB  - Attention alters three key properties of population neural activity - firing
      rate, rate variability, and shared variability between neurons. All three
      properties are well explained by a single canonical computation - normalization -
      that acts across hierarchically integrated brain systems. Combining data from
      rodents and nonhuman primates, we argue that cortical cholinergic modulation
      originating from the basal forebrain closely mimics the effects of directed
      attention on these three properties of population neural activity. Cholinergic
      modulation of the cortical microcircuit underlying normalization may represent a
      key biological basis for the rapid and flexible changes in population neuronal
      coding that are required by directed attention.

PMID- 29576465
TI  - Getting Serious about Variation: Lessons for Clinical Neuroscience (A Commentary
      on 'The Myth of Optimality in Clinical Neuroscience').

PMID- 29576466
TI  - William Henry Bragg, man and scientist, Nobel Laureate and First Professor of
      Physics, University of Adelaide 1886-1909.
AB  - In London, November 1915, a telegram was received at the home of William Henry
      Bragg from the secretary of the Academy of Science in Stockholm announcing the
      award of the Nobel Prize in Physics for "the analysis of crystal structures by
      means of X-rays". A second similar telegram was addressed to his 25 year old son
      William Lawrence Bragg (Jenkin, 2008). This article commemorates the centenary of
      that event and the unveiling of a bust of Sir William Bragg alongside that of his
      son, Sir Lawrence Bragg, on North Terrace in Adelaide where he spent 23 years of
      his early career.

PMID- 29576467
TI  - Apelin and apelin receptor at different stages of corpus luteum development and
      effect of apelin on progesterone secretion and 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD) in pigs.
AB  - Recent studies have suggested that apelin has a role in controlling female
      reproduction. The aims of the present study were, firstly, to investigate the
      gene expression (mRNA and protein) and immunolocalization of apelin and its
      receptor APJ in corpora lutea (CL) of pigs collected during the early (CL1),
      middle (CL2) and late (CL3) luteal phase. Using real time PCR and immunoblotting
      techniques, it was observed that apelin gene expression was similar in CL1 and
      CL2, and less in CL3, while relative abundance APJ mRNA and abundance of the
      protein were similar in CL1 and CL3 and greater in CL2. There was apelin staining
      in the cytoplasm of both small (SC) and large (LC) luteal cells with the greatest
      intensity in CL2. In the cytoplasm of CL1, only a few SC cells stained for APJ;
      in CL2, APJ was located in the cell membrane of LC and in the cytoplasm of SC;
      and in CL3 was located in the membrane with moderate cytoplasmic APJ staining.
      Intense APJ staining was noted in epithelium of blood vessels of CL2-3. Secondly,
      there was an effect of apelin on progesterone (P4) secretion in CL2 and on the
      molecular mechanisms of these cells. Stimulatory effects of apelin on P4
      secretion, 3beta-hydroxysteroid dehydrogenase (HSD) activity and protein
      abundance were observed and this was inhibited in response to APJ and adenosine
      5'-monophosphate-activated protein kinase (AMPKalpha) kinase blockers. In
      conclusion, the presence of apelin/APJ in the CL of pigs and stimulatory effects
      of apelin on P4 secretion and 3beta-HSD levels suggest potential auto/paracrine
      regulation by apelin in the luteal phase of the estrous cycle. Moreover, the
      involvement of APJ and AMPKalpha kinase in apelin activity in CL was confirmed.

PMID- 29576468
TI  - Retrieval and cryopreservation of sperm in spermatophores from cadaveric Indian
      white shrimp, Fenneropenaeus indicus (H. Milne Edwards, 1837).
AB  - This study focused on the quality of sperm obtained from spermatophores of
      cadaveric shrimp after long-term storage. Spermatophores were collected using the
      stripping method, which has resulted in maximum sperm viability when this
      approach was previously used. Cryoprotectants toxicity assessment of samples was
      conducted using dimethyl sulfoxide (DMSO), methanol (MeOH), ethylene glycol (EG),
      glycerol (Gly), dimethyl acetamide (DMA) and propylene glycol (PG) at different
      concentrations (5%, 10% and 30% v/v), prepared in Ca-F saline. Based on the
      results from the cryoprotectant toxicity assay, DMSO and MeOH were used
      individually as well as in combination for the subsequent study. Samples along
      with cryoprotectants were subjected to slow and fast freezing protocols (i.e. 
      0.5, and -10  degrees C/min to a final temperature of -80  degrees C) and were
      subsequently stored in LN2 (196  degrees C). Similarly, vitrification was
      performed by plunging the samples directly in to LN2. Samples of control and
      cryopreserved spermatophores that were stored for 45 days had sperm viabilities
      of 91.4 +/- 3.6% and 53.9 +/- 4.7%, respectively. Further observations with HOST
      and DNA integrity analyses of the cryopreserved sperm, resulted in percentages of
      45.6 +/- 4.2%; 58.1 +/- 1.7% compared to control values of 82.3 +/- 4.8%; 94.3 +/
      1.9%, respectively. Use of the one-step slow freezing protocol at the rate of 
      0.5  degrees C/min between 4  degrees C and -80  degrees C in LN2 with DMSO (5%)
      + MeOH (5%) was a desirable preservation strategy of spermatophores, compared to
      other freezing protocols. Unlike sperm viability, the HOST results affirm the
      fertility potential of the sperm that have the capacity to participate in the
      fertilization process. Thus, the results of this study demonstrate that long term
      storage of sperm in spermatophores of Fenneropenaeus indicus collected from
      cadaveric specimens can result in viable sperm after cryopreservation if extender
      (Ca-F saline) containing DMSO and MeOH are used.

PMID- 29576469
TI  - Pathogenesis of endometriosis: Interaction between Endocrine and inflammatory
      pathways.
AB  - Despite an estimated prevalence of 11% in women and plausible historical
      descriptions dating back to the 17th century, the etiology of endometriosis
      remains poorly understood. Classical theories of the histological origins of
      endometriosis are reviewed below. Clinical presentations are variable, and signs
      and symptoms do not correlate well with the extent of disease. In this summary,
      we have attempted to synthesize the growing evidence that hormonal and immune
      factors conspire to activate a local inflammatory microenvironment that
      encourages endometriosis to persist and elaborate mediators of its two cardinal
      symptoms: pain and infertility. Surprisingly, in the search for novel
      therapeutics for medical treatment of endometriosis, some compounds appear to
      have dual pharmacological functions, simultaneously modifying the endocrine and
      immune system facets of this complex gynecologic syndrome. We predict that these
      lead drugs will provide more therapeutic choices for patients in the future.

PMID- 29576470
TI  - Building consensus and standards in fetal growth restriction studies.
AB  - Fetal growth restriction is a pathologic condition in which the fetus fails to
      reach its biologically based growth potential. There is inconsistency in
      terminology, definition, monitoring, and management, both in clinical practice
      and in the existing literature. This hampers interpretation and comparison of
      cohorts and studies. Standardization is essential. With the lack of a golden
      standard, or the opportunity to come to empirical evidence, consensus procedures
      can help to establish standardization. Consensus procedures provide no new
      information but formulate an agreement (as second best in the absence of robust
      evidence) for clinical and/or research practice on the basis of existing data.
      Consensus agreements need to be updated when new evidence becomes available and
      can change over time. In this chapter, we address the different issues that lack
      uniformity in FGR studies and management. Furthermore, we discuss several
      consensus methods and recent consensus procedures regarding fetal growth
      restriction.

PMID- 29576471
TI  - Extremely Divergent Haplotypes in Two Toxin Gene Complexes Encode Alternative
      Venom Types within Rattlesnake Species.
AB  - Natural selection is generally expected to favor one form of a given trait within
      a population. The presence of multiple functional variants of traits involved in
      activities such as feeding, reproduction, or the defense against predators is
      relatively uncommon within animal species. The genetic architecture and
      evolutionary mechanisms underlying the origin and maintenance of such
      polymorphisms are of special interest. Among rattlesnakes, several instances of
      the production of biochemically distinct neurotoxic or hemorrhagic venom types
      within the same species are known. Here, we investigated the genetic basis of
      this phenomenon in three species and found that neurotoxic and hemorrhagic
      individuals of the same species possess markedly different haplotypes at two
      toxin gene complexes. For example, neurotoxic and hemorrhagic Crotalus scutulatus
      individuals differ by 5 genes at the phospholipase A2 (PLA2) toxin gene complex
      and by 11 genes at the metalloproteinase (MP) gene complex. A similar set of
      extremely divergent haplotypes also underlies alternate venom types within C.
      helleri and C. horridus. We further show that the MP and PLA2 haplotypes of
      neurotoxic C. helleri appear to have been acquired through hybridization with C.
      scutulatus-a rare example of the horizontal transfer of a potentially highly
      adaptive suite of genes. These large structural variants appear analogous to
      immunity gene complexes in host-pathogen arms races and may reflect the impact of
      balancing selection at the PLA2 and MP complexes for predation on different prey.

PMID- 29576472
TI  - Metabolic Costs of Feeding Predictively Alter the Spatial Distribution of
      Individuals in Fish Schools.
AB  - Group living is ubiquitous among animals [1, 2], but the exact benefits of group
      living experienced by individual groupmates is related to their spatial location
      within the overall group [3-5]. Individual variation in behavioral traits and
      nutritional state is known to affect interactions between individuals and their
      social group [6, 7], but physiological mechanisms underpinning collective animal
      behavior remain largely unexplored [8]. Here, we show that while fish at the
      front of moving groups are most successful at capturing food items, these
      individuals then show a systematic, post-feeding movement toward the rear of
      groups. Using observations of fish feeding in groups coupled with estimates of
      metabolic rate in fish consuming different meal sizes, we demonstrate that the
      magnitude of this shift in spatial position is directly related to the aerobic
      metabolic scope remaining after accounting for energetic costs of digestion.
      While previous work has shown that hungry individuals occupy anterior positions
      in moving groups [9, 10], our results show that the metabolic demand of food
      processing reduces the aerobic capacity available for locomotion in individuals
      that eat most, thus preventing them from maintaining leading positions. This
      basic trade-off between feeding and locomotor capacity could fundamentally
      dictate the spatial position of individuals within groups, perhaps obviating the
      role of individual traits in determining spatial preferences over shorter
      timescales (e.g., hours to days). This may be a general constraint for
      individuals within animal collectives, representing a key, yet overlooked,
      mediator of group functioning that could affect leadership, social information
      transfer, and group decision making.

PMID- 29576473
TI  - Host-Polarized Cell Growth in Animal Symbionts.
AB  - To determine the fundamentals of cell growth, we must extend cell biological
      studies to non-model organisms. Here, we investigated the growth modes of the
      only two rods known to widen instead of elongating, Candidatus Thiosymbion
      oneisti and Thiosymbion hypermnestrae. These bacteria are attached by one pole to
      the surface of their respective nematode hosts. By incubating live Ca. T. oneisti
      and T. hypermnestrae with a peptidoglycan metabolic probe, we observed that the
      insertion of new cell wall starts at the poles and proceeds inward, concomitantly
      with FtsZ-based membrane constriction. Remarkably, in Ca. T. hypermnestrae, the
      proximal, animal-attached pole grows before the distal, free pole, indicating
      that the peptidoglycan synthesis machinery is host oriented. Immunostaining of
      the symbionts with an antibody against the actin homolog MreB revealed that it
      was arranged medially-that is, parallel to the cell long axis-throughout the
      symbiont life cycle. Given that depolymerization of MreB abolished newly
      synthesized peptidoglycan insertion and impaired divisome assembly, we conclude
      that MreB function is required for symbiont widening and division. In conclusion,
      our data invoke a reassessment of the localization and function of the bacterial
      actin homolog.

PMID- 29576474
TI  - The Tyrosine Phosphatase STEP Is Involved in Age-Related Memory Decline.
AB  - Cognitive disabilities that occur with age represent a growing and expensive
      health problem. Age-associated memory deficits are observed across many species,
      but the underlying molecular mechanisms remain to be fully identified. Here, we
      report elevations in the levels and activity of the striatal-enriched phosphatase
      (STEP) in the hippocampus of aged memory-impaired mice and rats, in aged rhesus
      monkeys, and in people diagnosed with amnestic mild cognitive impairment (aMCI).
      The accumulation of STEP with aging is related to dysfunction of the ubiquitin
      proteasome system that normally leads to the degradation of STEP. Higher level of
      active STEP is linked to enhanced dephosphorylation of its substrates GluN2B and
      ERK1/2, CREB inactivation, and a decrease in total levels of GluN2B and brain
      derived neurotrophic factor (BDNF). These molecular events are reversed in aged
      STEP knockout and heterozygous mice, which perform similarly to young control
      mice in the Morris water maze (MWM) and Y-maze tasks. In addition, administration
      of the STEP inhibitor TC-2153 to old rats significantly improved performance in a
      delayed alternation T-maze memory task. In contrast, viral-mediated STEP
      overexpression in the hippocampus is sufficient to induce memory impairment in
      the MWM and Y-maze tests, and these cognitive deficits are reversed by STEP
      inhibition. In old LOU/C/Jall rats, a model of healthy aging with preserved
      memory capacities, levels of STEP and GluN2B are stable, and phosphorylation of
      GluN2B and ERK1/2 is unaltered. Altogether, these data suggest that elevated
      levels of STEP that appear with advancing age in several species contribute to
      the cognitive declines associated with aging.

PMID- 29576475
TI  - Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types
      Using Single-Cell RNA-Seq.
AB  - The identification of cell types and marker genes is critical for dissecting
      neural development and function, but the size and complexity of the brain has
      hindered the comprehensive discovery of cell types. We combined single-cell RNA
      seq (scRNA-seq) with anatomical brain registration to create a comprehensive map
      of the zebrafish habenula, a conserved forebrain hub involved in pain processing
      and learning. Single-cell transcriptomes of ~13,000 habenular cells with 4*
      cellular coverage identified 18 neuronal types and dozens of marker genes.
      Registration of marker genes onto a reference atlas created a resource for
      anatomical and functional studies and enabled the mapping of active neurons onto
      neuronal types following aversive stimuli. Strikingly, despite brain growth and
      functional maturation, cell types were retained between the larval and adult
      habenula. This study provides a gene expression atlas to dissect habenular
      development and function and offers a general framework for the comprehensive
      characterization of other brain regions.

PMID- 29576476
TI  - Unravelling the Molecular Determinants of Bee Sensitivity to Neonicotinoid
      Insecticides.
AB  - The impact of neonicotinoid insecticides on the health of bee pollinators is a
      topic of intensive research and considerable current debate [1]. As insecticides,
      certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and
      thiamethoxam, are as intrinsically toxic to bees as to the insect pests they
      target. However, this is not the case for all neonicotinoids, with honeybees
      orders of magnitude less sensitive to N-cyanoamidine compounds such as
      thiacloprid [2]. Although previous work has suggested that this is due to rapid
      metabolism of these compounds [2-5], the specific gene(s) or enzyme(s) involved
      remain unknown. Here, we show that the sensitivity of the two most economically
      important bee species to neonicotinoids is determined by cytochrome P450s of the
      CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation
      in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids
      does not reside in differences in their affinity for the receptor but rather in
      divergent metabolism by P450s. Functional expression of the entire CYP3 clade of
      P450s from honeybees identified a single P450, CYP9Q3, that metabolizes
      thiacloprid with high efficiency but has little activity against imidacloprid. We
      demonstrate that bumble bees also exhibit profound differences in their
      sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional
      ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid
      sensitivity in this species. Our results demonstrate that bee pollinators are
      equipped with biochemical defense systems that define their sensitivity to
      insecticides and this knowledge can be leveraged to safeguard bee health.

PMID- 29576477
TI  - Depletion of Maternal Cyclin B3 Contributes to Zygotic Genome Activation in the
      Ciona Embryo.
AB  - Most animal embryos display a delay in the activation of zygotic transcription
      during early embryogenesis [1]. This process is thought to help coordinate rapid
      increases in cell number during early development [2]. The timing of zygotic
      genome activation (ZGA) during the maternal-to-zygotic transition (MZT) remains
      uncertain despite extensive efforts. We explore ZGA in the simple
      protovertebrate, Ciona intestinalis. Single-cell RNA sequencing (RNA-seq) assays
      identified Cyclin B3 (Ccnb3) as a putative mediator of ZGA. Maternal Ccnb3
      transcripts rapidly diminish in abundance during the onset of zygotic
      transcription at the 8-cell and 16-cell stages. Disruption of Ccnb3 activity
      results in precocious activation of zygotic transcription, while overexpression
      abolishes normal activation. These observations suggest that the depletion of
      maternal Cyclin B3 products is a critical component of the MZT and ZGA. We
      discuss evidence that this mechanism might play a conserved role in the MZT of
      other metazoans, including mice and humans.

PMID- 29576479
TI  - Mixed methods formative evaluation of a collaborative care program to decrease
      risky opioid prescribing and increase non-pharmacologic approaches to pain
      management.
AB  - INTRODUCTION: Opioid prescribing and subsequent rates of serious harms have
      dramatically increased in the past two decades, yet there are still significant
      barriers to reduction of risky opioid regimens. This formative evaluation
      utilized a mixed-methods approach to identify barriers and factors that may
      facilitate the successful implementation of Primary Care-Integrated Pain Support
      (PIPS), a clinical program designed to support the reduction of risky opioid
      regimens while increasing the uptake of non-pharmacologic treatment modalities.
      METHODS: Eighteen Department of Veterans Affairs (VA) employees across three
      sites completed a survey consisting of the Organizational Readiness for
      Implementing Change (ORIC) scale; a subset of these individuals (n = 9) then
      completed a semi-structured qualitative phone interview regarding implementing
      PIPS within the VA. ORIC results were analyzed using descriptive statistics while
      interview transcripts were coded and sorted according to qualitative themes.
      RESULTS: Quantitative analysis based on ORIC indicated high levels of
      organizational readiness to implement PIPS. Interview analysis revealed several
      salient themes: system-level barriers such as tension among various pain
      management providers; patient-level barriers such as perception of support and
      tension between patient and provider; and facilitating factors of PIPS, such as
      the importance of the clinical pharmacist role. CONCLUSIONS: While organizational
      readiness for implementing PIPS appears high, modifications to our implementation
      facilitation strategy (e.g., establishing clinical pharmacists as champions;
      marketing PIPS to leadership as a way to improve VA opioid safety metrics) may
      improve capacity of the sites to implement PIPS successfully.

PMID- 29576478
TI  - Mammalian Oocytes Locally Remodel Follicular Architecture to Provide the
      Foundation for Germline-Soma Communication.
AB  - Germ cells develop in a microenvironment created by the somatic cells of the
      gonad [1-3]. Although in males, the germ and somatic support cells lie in direct
      contact, in females, a thick extracellular coat surrounds the oocyte, physically
      separating it from the somatic follicle cells [4]. To bypass this barrier to
      communication, narrow cytoplasmic extensions of the follicle cells traverse the
      extracellular coat to reach the oocyte plasma membrane [5-9]. These delicate
      structures provide the sole platform for the contact-mediated communication
      between the oocyte and its follicular environment that is indispensable for
      production of a fertilizable egg [8, 10-15]. Identifying the mechanisms
      underlying their formation should uncover conserved regulators of fertility. We
      show here in mice that these structures, termed transzonal projections (TZPs),
      are specialized filopodia whose number amplifies enormously as oocytes grow,
      enabling increased germ-soma communication. By creating chimeric complexes of
      genetically tagged oocytes and follicle cells, we demonstrate that follicle cells
      elaborate new TZPs that push through the extracellular coat to reach the oocyte
      surface. We further show that growth-differentiation factor 9, produced by the
      oocyte, drives the formation of new TZPs, uncovering a key yet unanticipated role
      for the germ cell in building these essential bridges of communication. Moreover,
      TZP number and germline-soma communication are strikingly reduced in
      reproductively aged females. Thus, the growing oocyte locally remodels follicular
      architecture to ensure that its developmental needs are met, and an inability of
      somatic follicle cells to respond appropriately to oocyte-derived cues may
      contribute to human infertility.

PMID- 29576480
TI  - Nutritional Support from the Intestinal Microbiota Improves Hematopoietic
      Reconstitution after Bone Marrow Transplantation in Mice.
AB  - Bone marrow transplantation (BMT) offers curative potential for patients with
      high-risk hematologic malignancies, but the post-transplantation period is
      characterized by profound immunodeficiency. Recent studies indicate that the
      intestinal microbiota not only regulates mucosal immunity, but can also
      contribute to systemic immunity and hematopoiesis. Using antibiotic-mediated
      microbiota depletion in a syngeneic BMT mouse model, here we describe a role for
      the intestinal flora in hematopoietic recovery after BMT. Depletion of the
      intestinal microbiota resulted in impaired recovery of lymphocyte and neutrophil
      counts, while recovery of the hematopoietic stem and progenitor compartments and
      the erythroid lineage were largely unaffected. Depletion of the intestinal
      microbiota also reduced dietary energy uptake and visceral fat stores. Caloric
      supplementation through sucrose in the drinking water improved post-BMT
      hematopoietic recovery in mice with a depleted intestinal flora. Taken together,
      we show that the intestinal microbiota contribute to post-BMT hematopoietic
      reconstitution in mice through improved dietary energy uptake.

PMID- 29576481
TI  - The Monocot-Specific Receptor-like Kinase SDS2 Controls Cell Death and Immunity
      in Rice.
AB  - Programmed cell death (PCD) plays critical roles in plant immunity but must be
      regulated to prevent excessive damage. The E3 ubiquitin ligase SPL11 negatively
      regulates PCD and immunity in plants. We show that SPL11 cell-death suppressor 2
      (SDS2), an S-domain receptor-like kinase, positively regulates PCD and immunity
      in rice by engaging and regulating SPL11 and related kinases controlling defense
      responses. An sds2 mutant shows reduced immune responses and enhanced
      susceptibility to the blast fungus Magnaporthe oryzae. Conversely, SDS2 over
      expression induces constitutive PCD accompanied by elevated immune responses and
      enhanced resistance to M. oryzae. SDS2 interacts with and phosphorylates SPL11,
      which in turn ubiquitinates SDS2, leading to its degradation. In addition, SDS2
      interacts with related receptor-like cytoplasmic kinases, OsRLCK118/176, that
      positively regulate immunity by phosphorylating the NADPH oxidase OsRbohB to
      stimulate ROS production. Thus, a plasma membrane-resident protein complex
      consisting of SDS2, SPL11, and OsRLCK118/176 controls PCD and immunity in rice.

PMID- 29576483
TI  - Response to letter to the editor: impact of bariatric surgery on outcomes of
      patients with nonalcoholic fatty liver disease: a nationwide inpatient sample
      analysis, 2004-2012.

PMID- 29576482
TI  - Lung Epithelial Cells Coordinate Innate Lymphocytes and Immunity against
      Pulmonary Fungal Infection.
AB  - Lung epithelial cells (LECs) are strategically positioned in the airway mucosa to
      provide barrier defense. LECs also express pattern recognition receptors and a
      myriad of immune genes, but their role in immunity is often concealed by the
      activities of "professional" immune cells, particularly in the context of fungal
      infection. Here, we demonstrate that NF-kappaB signaling in LECs is essential for
      immunity against the pulmonary fungal pathogen Blastomyces dermatitidis. LECs
      orchestrate innate antifungal immunity by augmenting the numbers of interleukin
      17A (IL-17A)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      producing innate lymphocytes, specifically "natural" Th17 (nTh17) cells. Innate
      lymphocyte-derived IL-17A and GM-CSF in turn enable phagocyte-driven fungal
      killing. LECs regulate the numbers of nTh17 cells via the production of
      chemokines such as CCL20, a process dependent on IL-1alpha-IL-1 receptor (IL-1R)
      signaling on LECs. Therefore, LECs orchestrate IL-17A- and GM-CSF-mediated
      immunity in an IL-1R-dependent manner and represent an essential component of
      innate immunity to pulmonary fungal pathogens.

PMID- 29576484
TI  - Laparoscopic SADI-S as a salvage procedure for failed gastric bypass and sleeve
      gastrectomy: How I do it.

PMID- 29576485
TI  - Preoperative Glycemic Control Predicts Perioperative Serum Glucose Levels in
      Patients Undergoing Total Joint Arthroplasty.
AB  - BACKGROUND: Diabetic patients undergoing total joint arthroplasty (TJA) with
      postoperative hyperglycemia >200 mg/dL have increased the risk of prosthetic
      joint infection (PJI). We investigated the correlation between preoperative
      hemoglobin A1c (A1c) and postoperative hyperglycemia in diabetic patients
      undergoing TJA. METHODS: A retrospective review of 773 diabetic patients
      undergoing TJA was conducted. A Youden's J computational analysis determined the
      A1c where postoperative glucose levels >200 mg/dL were statistically more likely.
      Patients were then stratified into 3 groups: A1c <7%, A1c 7.0-8.0%, and A1c
      >8.0%. Outcomes included the highest postoperative in-hospital serum glucose
      level and PJI. RESULTS: We determined an A1c >7.45% resulted in a greater chance
      of postoperative hyperglycemia >200 mg/dL. Average postoperative serum glucose
      increased with A1c (A1c < 7 = 167 mg/dL, A1c 7.0-8.0 = 240 mg/dL, and A1c > 8 =
      276 mg/dL, P < .0001). PJI did not statistically increase with A1c (2.25%, 1.99%,
      and 4.55%, respectively, P = .4319). CONCLUSION: Preoperative hemoglobin A1c
      levels correlate with postoperative glucose levels. We recommend using an A1c
      cutoff of 7.45% for patients undergoing TJA and suggest that caution should be
      exercised in patients with elevated A1c levels undergoing TJA.

PMID- 29576486
TI  - Characterization of Outcomes of 2-Stage Exchange Arthroplasty in the Treatment of
      Prosthetic Joint Infections.
AB  - BACKGROUND: Two-stage revision is the preferred treatment for prosthetic hip and
      knee infections in the United States. Recent studies have questioned the true
      success rate of this treatment. The purpose of this study is to investigate
      outcomes of prosthetic hip and knee infections undergoing resection arthroplasty
      and spacer insertion at a single institution. METHODS: We identified 103 patients
      who underwent prosthesis resection and spacer placement for infection over a 10
      year period. Twenty-three cases were excluded based on preset exclusion criteria
      leaving 80 cases (56 knees, 24 hips). A retrospective review was performed to
      examine the outcomes of these patients. RESULTS: Following spacer placement but
      before reimplantation, 9 (11.25%) of the 80 joints underwent repeat debridement
      and spacer exchange for persistent infection. Twenty-four (30.00%) patients had a
      serious complication during their treatment course. Fourteen (17.50%) patients
      never underwent reimplantation. Of these, 10 continued with spacer retention, 2
      had resection arthroplasty, and 1 each had an amputation and an arthrodesis. Of
      the 66 patients with successful reimplantation, 48 (72.70%) remained infection
      free at most recent follow-up. CONCLUSIONS: Two-stage revision does not result in
      the high rates of cure reported previously, when taking into account the
      substantial number of patients who never undergo the subsequent reimplantation
      surgery. Of those who underwent reimplantation in our study, many required
      additional spacer exchange or had complications. Surgeons and patients should
      consider these outcomes when discussing the treatment of prosthetic hip and knee
      infections.

PMID- 29576487
TI  - Total Knee Arthroplasty With Patellar Retention: The Severity of Patellofemoral
      Osteoarthritis Did Not Affect the Clinical and Radiographic Outcomes.
AB  - BACKGROUND: The purpose of this study is to compare the clinical and radiographic
      outcomes of total knee arthroplasty (TKA) with patellar retention in accordance
      with the severity of patellofemoral arthritis. METHODS: We retrospectively
      reviewed patients who underwent TKA with patellar retention using the NexGen LPS
      or LPS-flex system between September 2010 and May 2015. The radiographic severity
      of patellofemoral arthritis was categorized according to the Iwano classification
      system, and subjects were divided into mild (stage 0-I) and moderate to severe
      (stage II-IV) groups. Clinical outcomes were evaluated using the Hospital for
      Special Surgery score, Knee Society Score, function score, Western Ontario and
      McMaster Universities Osteoarthritis Index, and Feller score. Radiographic
      outcomes were assessed using the congruence angle, patellar tilt angle, and
      lateral patellar displacement. The minimum follow-up for clinical and
      radiographic evaluation was 2 years. Clinical and radiographic outcomes were
      compared between the 2 groups preoperatively and at the time of the last follow
      up. RESULTS: Four hundred seventy-four knees were enrolled and assigned to mild
      (n = 208) or moderate to severe (n = 266) groups. The preoperative Feller score
      was significantly lower in the moderate to severe group (P = .030), whereas the
      postoperative clinical and radiographic results did not differ significantly
      between the 2 groups. CONCLUSION: Clinical and radiographic outcomes did not
      differ in accordance with the severity of patellofemoral arthritis after a
      minimum 2 years of follow-up of patients treated with TKA with patellar
      retention. Good outcomes were obtained with patellar retention in TKA, even in
      patients with advanced patellofemoral osteoarthritis.

PMID- 29576488
TI  - Can a Single-Use and Patient-Specific Instrumentation Be Reliably Used in Primary
      Total Knee Arthroplasty? A Multicenter Controlled Study.
AB  - BACKGROUND: The aim of this controlled multicenter study is to evaluate the
      clinical and radiologic outcomes of primary total knee arthroplasty (TKA) using
      single-use fully disposable and patient-specific cutting guides (SU) and compare
      the results to those obtained with traditional patient-specific cutting guides
      (PSI) vs conventional instrumentation (CI). METHODS: Seventy consecutive patients
      had their TKA performed using SU. They were compared to 140 historical patients
      requiring TKA that were randomized to have the procedure performed using PSI vs
      CI. The primary measure outcome was mechanical axis as measured on a standing
      long-leg radiograph using the hip-knee-ankle angle. Secondary outcome measures
      were Knee Society and Oxford knee scores, operative time, need for postoperative
      transfusion, and length of hospital stay. RESULTS: The mean hip-knee-ankle value
      was 179.8 degrees  (standard deviation [SD] 3.1 degrees ), 179.2 degrees  (SD 2.9
      degrees ), and 178.3 degrees  (SD 2.5 degrees ) in the CI, PSI and SU groups,
      respectively (P = .0082). Outliers were identified in 16 of 65 (24.6%), 15 of 67
      (22.4%), and 14 of 70 (20.0%) knees in the CI, PSI, and SU group, respectively (P
      = .81). There was no significant difference in the clinical results (P = .29 and
      .19, respectively). Operative time, number of unit transfusion, and length of
      hospital stay were not significantly different between the 3 groups (P = .45,
      .31, and 0.98, respectively). CONCLUSION: The use of an SU in TKA provided
      similar clinical and radiologic results to those obtained with traditional PSI
      and CI. The potential economic advantages of single-use instrumentation in
      primary TKA require further investigation.

PMID- 29576489
TI  - Outcomes of Primary Total Knee Arthroplasty in Patients With Parkinson's Disease.
AB  - BACKGROUND: Parkinson's disease is a degenerative disorder causing rigidity,
      bradykinesia, and tremor of the motor system. There is significant paucity of
      evidence regarding whether total knee arthroplasty (TKA) is of benefit in
      patients with both Parkinson's disease and osteoarthritis. We aimed to compare
      outcomes and complications of TKA between patients with Parkinson's disease and
      those without. METHODS: A cohort of 43 knees from 35 patients with Parkinson's
      disease who received a primary TKA between January 2004 and December 2015 were
      retrospectively extracted from a private clinical database held by 2 surgeons and
      compared to an age and gender-matched control group of 50 knees from 41 patients.
      TKAs were performed by 2 surgeons at 1 tertiary private hospital.The indication
      for TKA in both groups was osteoarthritis. Difference between preoperative and 1
      year range of movement (ROM) and 12-point Oxford Knee Score (OKS) was assessed
      using Student's unpaired t-test. Postoperative complications and revision
      procedures were also recorded during the follow-up period. The minimal clinically
      important difference for OKS at 1-year follow-up, defined as improvement of >=6,
      was also assessed. RESULTS: In the Parkinson's group, mean ROM improvement was 14
      degrees  (100 degrees  preoperatively to 114 degrees  at 12 months), compared to
      12 degrees  in the control group (102 degrees -114 degrees , respectively). Mean
      OKS improvement was 15 in the Parkinson's group (23 preoperatively to 38 at 12
      months) compared to 17 in the control group (23 and 40, respectively.) No
      significant difference was identified between the 2 groups for either ROM (P =
      .96) or OKS (P = .45.) All Parkinson's patients achieved the minimal clinically
      important difference at 1-year follow-up. There were no mortalities during the
      study follow-up period and no significant difference in complication rates
      between the 2 groups (P = .41). CONCLUSION: Parkinson's disease was not
      associated with poorer functional outcomes or increased complications compared to
      controls in our study. We suggest that Parkinson's disease is not an absolute
      contraindication to TKA.

PMID- 29576490
TI  - Is the inclinometer a valid measure of thoracic kyphosis? A cross-sectional
      study.
AB  - BACKGROUND: Radiographs are used to monitor thoracic kyphosis in individuals with
      certain pathologies (e.g. osteoporosis), exposing patients to potentially harmful
      radiation. Thus, other measures for monitoring the progression of thoracic
      kyphosis are desirable. The gravity-dependent inclinometer has been shown to be
      reliable but its validity as a measure of thoracic kyphosis has not been
      investigated. OBJECTIVES: To determine the validity of the gravity-dependent
      (analogue) inclinometer for measuring thoracic kyphosis. DESIGN: Cross-sectional
      study. METHOD: Participants (n=78) were recruited as part of a larger study of
      shoulder impingement syndrome. Healthy participants (n=39) were age and gender
      matched to the shoulder impingement syndrome group (n=39). Measurements of
      thoracic kyphosis using a gravity-dependent inclinometer were compared with
      modified Cobb angle results obtained from a sagittal view of lateral radiographs.
      A Bland-Altman plot assessed agreement. The Pearson correlation coefficient and
      linear regression was used to determine the association between modified Cobb
      angles and inclinometer measurements. RESULTS: The Bland-Altman plot demonstrated
      good agreement. The Pearson correlation coefficient, r=0.62 (p<0.001), and linear
      regression model established a strong association between the thoracic kyphosis
      angle from the inclinometer readings and the modified Cobb angle measured from
      the radiographs (beta=0.47, 95% CI 0.29, 0.65, p<0.001, R2=0.52, n=78). Age as a
      confounder was included in the model (beta=0.35, 95% CI 0.19, 0.51, p<0.001).
      CONCLUSIONS: The gravity-dependent (analogue) inclinometer produces angles that
      are comparable to the modified Cobb angle obtained from radiographs, establishing
      its criterion validity as a safe clinical tool for measuring thoracic kyphosis.

PMID- 29576491
TI  - Thoracoscopic resection of an epiphrenic diverticulus in ventral decubitus (with
      video).

PMID- 29576492
TI  - Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour
      or not contour the hippocampus?
AB  - PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients
      treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS:
      Retrospective hippocampal dosimetric analysis performed on 22 patients with one
      to four brain metastases treated with fractionated stereotactic radiotherapy
      using volumetric intensity-modulated arc therapy. Original plans did not include
      hippocampus as avoidance structure in optimization criteria; hippocampus was
      retrospectively delineated on magnetic resonance coregistered with planning CT
      and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a
      single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy,
      D100%=Dmin<9Gy. Assuming a alpha/beta ratio of 2Gy, biologically equivalent dose
      in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in
      cases where hippocampal constraints were not respected in the original plan.
      RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out
      of 22 cases. The constraints were not respected in patients with more than one
      metastatic lesion and in three patients with only one lesion. Considering all
      exceeded constraints values in non-hippocampal sparing plans, the 50% of them was
      respected after replanning. No significant differences were found among
      conformity and homogeneity index between non-hippocampal sparing and hippocampal
      sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal
      sparing plans significantly decreases dose to hippocampus assuring an equal
      target coverage and organs at risk avoiding.

PMID- 29576493
TI  - Aspiration Thrombectomy versus Conventional Catheter-Directed Thrombolysis as
      First-Line Treatment for Noniatrogenic Acute Lower Limb Ischemia.
AB  - PURPOSE: To examine the efficacy, safety, and procedural costs of percutaneous
      aspiration thrombectomy (PAT) as a first-line treatment for noniatrogenic acute
      lower limb ischemia (ALI) compared with conventional catheter-directed
      thrombolysis (CDT). MATERIALS AND METHODS: All patients who underwent
      endovascular intervention for ALI from January 2015 to August 2017 were included.
      Fifteen patients were treated with the use of primary PAT and 27 patients were
      treated with the use of primary CDT. The primary end point was complete thrombus
      clearance with improvement in Thrombolysis in Myocardial Infarction (TIMI) score.
      Adjunctive treatment for thrombus removal was considered to indicate technical
      failure. Treatment of underlying chronic disease was not considered to indicate
      technical failure. Procedural costs for each patient were calculated by itemizing
      all disposable equipment, facility overheads, and staff costs. RESULTS: Of the 15
      primary PAT patients, technical success was achieved in 8 (53%); the remaining 7
      (47%) required adjunctive CDT. Of the 27 primary CDT patients, technical success
      was achieved in 25 (89%); the remaining 2 (11%) required adjunctive PAT. There
      were 4 complications in the primary PAT group: 2 were procedure related and of a
      minor grade. There were 8 complications in the primary CDT group: All were
      procedure-related, including 2 major groin/retroperitoneal hemorrhage and 1 death
      from intracranial hemorrhage. Limb salvage was attained in all patients. There
      were no significant differences in average procedural costs per patient between
      the 2 groups. CONCLUSIONS: First-line use of PAT for endovascular treatment of
      ALI can reduce the need for CDT, with no significant cost difference.

PMID- 29576494
TI  - Combined Fluoroscopy and Ultrasound-Guided Transjugular Kidney Biopsy in
      Cirrhotic Patients.
AB  - PURPOSE: To evaluate the safety and diagnostic yield of combined fluoroscopy and
      ultrasound-guided transjugular kidney biopsy (TJKB) in cirrhotic patients with
      suspected renal parenchymal disease. MATERIALS AND METHODS: A retrospective
      review was made of 27 patients (21 men; overall mean age 44.7 y) who underwent
      TJKB from June 2013 to June 2016; 21 patients had coagulopathy and/or
      thrombocytopenia, 4 underwent simultaneous TJKB with transjugular liver biopsy,
      and 1 patient each had severe obesity and gross ascites. All procedures were
      performed with the use of fluoroscopy and simultaneous transabdominal ultrasound
      guidance. The data were analyzed for number of passes taken, number of glomeruli
      in the tissue cores, adequacy of tissue core for histopathologic diagnosis, and
      incidence and severity of complications. RESULTS: The average number of passes
      per case was 3.6 (range 2-6). The total length of tissue cores ranged from 0.4 cm
      to 2.5 cm. The mean numbers of glomeruli per procedure on light microscopy were
      6.7 (range 0-17). Diagnostic biopsy specimens were obtained in 23 out of 27
      patients (85%). Eleven patients had minor complications. One patient had major
      complication in the form of hemoglobin drop of 2.1 mg/dL which required
      embolization and blood transfusion. CONCLUSIONS: Combined use of fluoroscopy and
      ultrasound guidance for TJKB yielded adequate tissue samples with fewer passes
      and a low rate of complications in high-risk patients with cirrhosis.

PMID- 29576495
TI  - The real-world effectiveness of vedolizumab on intestinal and articular outcomes
      in inflammatory bowel diseases.
AB  - BACKGROUND: The effectiveness of vedolizumab in real-world practice is under
      evaluation, while its role in inflammatory bowel disease-associated
      spondyloarthritis is still unclear. AIMS: To report real-world data about the
      effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22
      weeks of treatment. METHODS: Web-based data from the cohort of the Sicilian
      Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a
      prospective multicentre observational study. RESULTS: 163 patients (84 with
      Crohn's disease and 79 with ulcerative colitis) were included. At week 10, a
      steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a
      steroid-free remission was obtained in 40.8% of patients. A response on articular
      symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%)
      patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%)
      patients at week 22. The only factor associated with articular response was the
      coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, p =
      0.05; at week 22: OR 5.600, p = 0.08). CONCLUSIONS: Vedolizumab showed good
      effectiveness after 10 and 22 weeks of treatment. A subset of patients reported
      improvement also on articular symptoms, probably as a consequence of the
      concomitant control of gut inflammation.

PMID- 29576496
TI  - Corrigendum to 'Respiratory muscle training increases respiratory muscle strength
      and reduces respiratory complications after stroke: a systematic review' [J
      Physiother 2016;62:138-144].

PMID- 29576497
TI  - Urine Proteome Profiling Predicts Lung Cancer from Control Cases and Other
      Tumors.
AB  - Development of noninvasive, reliable biomarkers for lung cancer diagnosis has
      many clinical benefits knowing that most of lung cancer patients are diagnosed at
      the late stage. For this purpose, we conducted proteomic analyses of 231 human
      urine samples in healthy individuals (n=33), benign pulmonary diseases (n=40),
      lung cancer (n=33), bladder cancer (n=17), cervical cancer (n=25), colorectal
      cancer (n=22), esophageal cancer (n=14), and gastric cancer (n=47) patients
      collected from multiple medical centers. By random forest modeling, we nominated
      a list of urine proteins that could separate lung cancers from other cases. With
      a feature selection algorithm, we selected a panel of five urinary biomarkers
      (FTL: Ferritin light chain; MAPK1IP1L: Mitogen-Activated Protein Kinase 1
      Interacting Protein 1 Like; FGB: Fibrinogen Beta Chain; RAB33B: RAB33B, Member
      RAS Oncogene Family; RAB15: RAB15, Member RAS Oncogene Family) and established a
      combinatorial model that can correctly classify the majority of lung cancer cases
      both in the training set (n=46) and the test sets (n=14-47 per set) with an AUC
      ranging from 0.8747 to 0.9853. A combination of five urinary biomarkers not only
      discriminates lung cancer patients from control groups but also differentiates
      lung cancer from other common tumors. The biomarker panel and the predictive
      model, when validated by more samples in a multi-center setting, may be used as
      an auxiliary diagnostic tool along with imaging technology for lung cancer
      detection.

PMID- 29576499
TI  - A response to comments by Dr. Mohammad Alwardat on "Safety of repeated sessions
      of transcranial direct current stimulation: A systematic review".

PMID- 29576498
TI  - Evidence of transcranial direct current stimulation-generated electric fields at
      subthalamic level in human brain in vivo.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising brain
      modulation technique for several disease conditions. With this technique, some
      portion of the current penetrates through the scalp to the cortex and modulates
      cortical excitability, but a recent human cadaver study questions the amount.
      This insufficient intracerebral penetration of currents may partially explain the
      inconsistent and mixed results in tDCS studies to date. Experimental validation
      of a transcranial alternating current stimulation-generated electric field (EF)
      in vivo has been performed on the cortical (using electrocorticography, ECoG,
      electrodes), subcortical (using stereo electroencephalography, SEEG, electrodes)
      and deeper thalamic/subthalamic levels (using DBS electrodes). However, tDCS
      generated EF measurements have never been attempted. OBJECTIVE: We aimed to
      demonstrate that tDCS generates biologically relevant EF as deep as the
      subthalamic level in vivo. METHODS: Patients with movement disorders who have
      implanted deep brain stimulation (DBS) electrodes serve as a natural experimental
      model for thalamic/subthalamic recordings of tDCS-generated EF. We measured
      voltage changes from DBS electrodes and body resistance from tDCS electrodes in
      three subjects while applying direct current to the scalp at 2 mA and 4 mA over
      two tDCS montages. RESULTS: Voltage changes at the level of deep nuclei changed
      proportionally with the level of applied current and varied with different tDCS
      montages. CONCLUSIONS: Our findings suggest that scalp-applied tDCS generates
      biologically relevant EF. Incorporation of these experimental results may improve
      finite element analysis (FEA)-based models.

PMID- 29576500
TI  - Dualistic effect of pallidal deep brain stimulation on motor speech disorders in
      dystonia.
AB  - BACKGROUND: Although pallidal deep brain stimulation (GPi-DBS) is an effective
      treatment for dystonia, it may cause important stimulation-induced side-effects
      such as hypokinetic dysarthria or stuttering. However, the reasons behind the
      occurrence of these side-effects remain unknown. OBJECTIVE: To objectively
      investigate the impact of GPi-DBS on patients with dystonia on speech fluency,
      intelligibility, and key aspects of hyperkinetic and hypokinetic dysarthria.
      METHODS: Speech was systematically evaluated in 19 dystonic patients with GPi
      DBS. Each patient was tested twice within one day in both the GPi-DBS ON and GPi
      DBS OFF stimulation conditions. A control sample of 19 matched healthy speakers
      underwent the same speech assessment. RESULTS: We observed an improvement of
      hyperkinetic dysarthria symptoms in 47% and an aggravation of hypokinetic
      dysarthria symptoms in 26% of patients with the GPi-DBS switched ON. A higher
      stimulus intensity was found in a group of patients in whom the hypokinetic
      dysarthria worsened with the GPi-DBS ON when compared to other dystonic patients
      (p = 0.02). Furthermore, we revealed a significant increase of dysfluent words in
      the GPi-DBS ON when compared to OFF condition (p = 0.001) associated with the
      shorter distance of the active contact localization along the medio-lateral
      direction (r = -0.70, p = 0.005). CONCLUSION: This study provides evidence of
      dualistic effects of GPi-DBS on speech in dystonia manifested as an improvement
      of hyperkinetic or a deterioration of hypokinetic dysarthria. Our findings
      suggest that lower stimulation parameters and placement of active contacts more
      laterally in the internal globus pallidus should be preferred to avoid the
      possible side effects of hypokinetic dysarthria and dysfluency.

PMID- 29576501
TI  - Intrastriatal transplantation of stem cells from human exfoliated deciduous teeth
      reduces motor defects in Parkinsonian rats.
AB  - BACKGROUND: This study explored the neural differentiation and therapeutic
      effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model
      of Parkinson's disease (PD). METHODS: The SHED were isolated from fresh dental
      pulp and were induced to differentiate to neurons and dopamine neurons by
      inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase
      conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and
      FGF8 in vitro. The neural-primed SHED were transplanted to the striatum of 6
      hydroxydopamine (6-OHDA)-induced PD rats to evaluate their neural differentiation
      and functions in vivo. RESULTS: These SHED were efficiently differentiated to
      neurons (62.7%) and dopamine neurons (42.3%) through a newly developed method.
      After transplantation, the neural-induced SHED significantly improved recovery of
      the motor deficits of the PD rats. The grafted SHED were differentiated into
      neurons (61%), including dopamine neurons (22.3%), and integrated into the host
      rat brain by forming synaptic connections. Patch clamp analysis showed that
      neurons derived from grafted SHED have the same membrane potential profile as
      dopamine neurons, indicating these cells are dopamine neuron-like cells. The
      potential molecular mechanism of SHED transplantation in alleviating motor
      deficits of the rats is likely to be mediated by neuronal replacement and immune
      modulation as we detected the transplanted dopamine neurons and released immune
      cytokines from SHED. CONCLUSION: Using neural-primed SHED to treat PD showed
      significant restorations of motor deficits in 6-OHDA-induced rats. These
      observations provide further evidence that SHED can be used for cell-based
      therapy of PD.

PMID- 29576502
TI  - The healthy donor profile of immunoregulatory soluble mediators is altered by
      stem cell mobilization and apheresis.
AB  - BACKGROUND: Peripheral blood stem cells from healthy donors mobilized by
      granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by
      leukapheresis are commonly used for allogeneic stem cell transplantation.
      METHODS: Plasma levels of 38 soluble mediators (cytokines, soluble adhesion
      molecules, proteases, protease inhibitors) were analyzed in samples derived from
      healthy stem cell donors before G-CSF treatment and after 4 days, both
      immediately before and after leukapheresis. RESULTS: Donors could be classified
      into two main subsets based on their plasma mediator profile before G-CSF
      treatment. Seventeen of 36 detectable mediators were significantly altered by G
      CSF; generally an increase in mediator levels was seen, including pro
      inflammatory cytokines, soluble adhesion molecules and proteases. Several
      leukocyte- and platelet-released mediators were increased during apheresis. Both
      plasma and graft mediator profiles were thus altered and showed correlations to
      graft concentrations of leukocytes and platelets; these concentrations were
      influenced by the apheresis device used. Finally, the mediator profile of the
      allotransplant recipients was altered by graft infusion, and based on their day
      +1 post-transplantation plasma profile our recipients could be divided into two
      major subsets that differed in overall survival. DISCUSSION: G-CSF alters the
      short-term plasma mediator profile of healthy stem cell donors. These effects
      together with the leukocyte and platelet levels in the graft determine the
      mediator profile of the stem cell grafts. Graft infusion also alters the systemic
      mediator profile of the recipients, but further studies are required to clarify
      whether such graft-induced alterations have a prognostic impact.

PMID- 29576503
TI  - Effective treatment of progressive MS remains elusive.

PMID- 29576504
TI  - Multiple sclerosis.
AB  - Multiple sclerosis continues to be a challenging and disabling condition but
      there is now greater understanding of the underlying genetic and environmental
      factors that drive the condition, including low vitamin D levels, cigarette
      smoking, and obesity. Early and accurate diagnosis is crucial and is supported by
      diagnostic criteria, incorporating imaging and spinal fluid abnormalities for
      those presenting with a clinically isolated syndrome. Importantly, there is an
      extensive therapeutic armamentarium, both oral and by infusion, for those with
      the relapsing remitting form of the disease. Careful consideration is required
      when choosing the correct treatment, balancing the side-effect profile with
      efficacy and escalating as clinically appropriate. This move towards more
      personalised medicine is supported by a clinical guideline published in 2018.
      Finally, a comprehensive management programme is strongly recommended for all
      patients with multiple sclerosis, enhancing health-related quality of life
      through advocating wellness, addressing aggravating factors, and managing
      comorbidities. The greatest remaining challenge for multiple sclerosis is the
      development of treatments incorporating neuroprotection and remyelination to
      treat and ultimately prevent the disabling, progressive forms of the condition.

PMID- 29576506
TI  - Overexpressing dominant-negative FGFR2-IIIb impedes lung branching morphogenesis
      in pigs.
AB  - Genetic studies with mouse models have shown that fibroblast growth factor
      receptor 2-IIIb (FGFR2-IIIb) plays crucial roles in lung development and
      differentiation. To evaluate the effect of FGFR2-IIIb in pig lung development, we
      employed somatic cell nuclear transfer (SCNT) technology to generate transgenic
      pig fetuses overexpressing the transmembrane (dnFGFR2-IIIb-Tm) and soluble
      (dnFGFR2-IIIb-HFc) forms of the dominant-negative human FGFR2-IIIb driven by the
      human surfactant protein C (SP-C) promoter, which was specifically expressed in
      lung epithelia. Eight dnFGFR2-IIIb-Tm transgenic and twelve dnFGFR2-IIIb-HFc
      transgenic pig fetuses were collected from three and two recipient sows,
      respectively. Repression of FGFR2-IIIb in lung epithelia resulted in smaller
      lobes and retardation of alveolarization in both forms of dnFGFR2-IIIb transgenic
      fetuses. Moreover, the dnFGFR2-IIIb-HFc transgenic ones showed more deterioration
      in lung development. Our results demonstrate that disruption of FGFR2-IIIb
      signaling in the epithelium impedes normal branching and alveolarization in pig
      lungs, which is less severe than the results observed in transgenic mice. The
      dnFGFR2-IIIb transgenic pig is a good model for the studies of blastocyst
      complementation as well as the mechanisms of lung development and organogenesis.

PMID- 29576507
TI  - A novel lncRNA, Lnc-OC1, promotes ovarian cancer cell proliferation and migration
      by sponging miR-34a and miR-34c.
AB  - Long non-coding RNAs (lncRNAs) have been reported to be of great importance in
      tumorigenesis and progression of a variety of cancers. However, the role of
      lncRNAs in ovarian cancer (OC) remains largely unknown. In the present study, we
      identified a novel lncRNA, LOC100288181 (named as Lnc-OC1), which acted as a key
      regulator in the development and progression of OC. The combined Gene Expression
      Omnibus (GEO) database analysis revealed that Lnc-OC1 was significantly
      upregulated in OC tissues and Kaplan-Meier survival analysis confirmed that high
      Lnc-OC1 expression was associated with poor prognosis of OC patients.
      Importantly, we also demonstrated that knockdown of Lnc-OC1 suppressed cell
      proliferation, colony formation, invasion and migration in vitro and inhibited
      tumorigenicity in vivo. Mechanistically, Lnc-OC1 repressed the expression of
      endogenous miR-34a and miR-34c as a sponge and vice versa. Moreover, rescue
      experiments demonstrated that the oncogenic function of Lnc-OC1 at least
      partially depended on suppressing miR-34a and miR-34c. In conclusion, our results
      suggest that the Lnc-OC1-miR-34a/34c axis may play a pivotal role in OC, and may
      serve as a potential diagnostic biomarker and a powerful therapeutic target for
      OC.

PMID- 29576508
TI  - The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial
      ischemia reperfusion injury.
AB  - Sentrin-specific protease 3 (SENP3), a member of the desumoylating enzyme family,
      is known as a redox sensor and could regulate multiple cellular signaling
      pathways. However, its implication in myocardial ischemia reperfusion (MIR)
      injury is unclear. Here, we observed that SENP3 was expressed and upregulated in
      the mouse heart depending on reactive oxygen species (ROS) production in response
      to MIR injury. By utilizing siRNA-mediated cardiac specific gene silencing, SENP3
      knockdown was demonstrated to significantly reduce MIR-induced infarct size and
      improve cardiac function. Mechanistic studies indicated that SENP3 silencing
      ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum
      (ER) stress and mitochondrial-mediated apoptosis pathways. By contrast,
      adenovirus-mediated cardiac SENP3 overexpression significantly exaggerated MIR
      injury. Further molecular analysis revealed that SENP3 promoted mitochondrial
      translocation of dynamin-related protein 1 (Drp1) in reperfused myocardium. In
      addition, mitochondrial division inhibitor-1 (Mdivi-1), a pharmacological
      inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial
      abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken
      together, we provide the first direct evidence that SENP3 upregulation pivotally
      contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3
      suppression may hold therapeutic promise for constraining MIR injury.

PMID- 29576509
TI  - Synthesis of new 4-aryloxy-N-arylanilines and their inhibitory activities against
      succinate-cytochrome c reductase.
AB  - Succinate-cytochrome c reductase (SCR) is composed of a mixture of mitochondrial
      complex II (succinate-ubiquinone oxidoreductase) and complex III (cytochrome bc1
      complex). Meanwhile, complexes II and III are two promising targets of numerous
      antibiotics and fungicides. With an aim to identify new lead structures for SCR,
      complex II or III, a new series of 4-aryloxy-N-arylanilines were synthesized by
      introducing a 4-aryloxy phenyl group as one of the aryl groups in diaryl amines.
      With the economic Cu(OAc)2.H2O as the optimal copper promoter, a simple and
      facile protocol was utilized to afford 24 target products in 56-93% yields.
      Furthermore, extensive screening results suggested variable inhibitory activities
      of these compounds against SCR. Exceptionally, compounds 7k-7n showed excellent
      inhibition potency with their IC50 values in the nanomolar range, demonstrating
      higher potency than the commercial controls (penthiopyrad and azoxystrobin) by
      over one order of magnitude.

PMID- 29576510
TI  - Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl
      tethered anthraquinones.
AB  - Structural features from the anticancer prodrug nemorubicin (MMDX) and the DNA
      binding molecule DRAQ5TM were used to prepare anthraquinone-based compounds,
      which were assessed for their potential to interrogate cytochrome P450 (CYP)
      functional activity and localisation. 1,4-disubstituted anthraquinone 8 was shown
      to be 5-fold more potent in EJ138 bladder cancer cells after CYP1A2
      bioactivation. In contrast, 1,5-bis((2-morpholinoethyl)amino) substituted
      anthraquinone 10 was not CYP-bioactivated but was shown to be fluorescent and
      subsequently photo-activated by a light pulse (at a bandwidth 532-587 nm),
      resulting in punctuated foci accumulation in the cytoplasm. It also showed low
      toxicity in human osteosarcoma cells. These combined properties provide an
      interesting prospective approach for opto-tagging single or a sub-population of
      cells and seeking their location without the need for continuous monitoring.

PMID- 29576511
TI  - Thermal decomposition mechanisms of poly(vinyl chloride): A computational study.
AB  - The studies on the pyrolysis mechanisms of waste PVC contribute to development
      and application of pyrolysis technology for mixed waste plastics. In the article,
      the thermal decomposition mechanisms of model compound of poly(vinyl chloride)
      (PVC) have been investigated by employing density functional theory methods at
      M06-2X/6-31++G(d,p) level in order to illuminate the elimination of HCl and the
      formation of hydrocarbons. Various possible pyrolysis paths for the formation of
      main products were proposed, and the thermodynamic and kinetic parameters in
      every path were calculated. The calculation results show that the HCl elimination
      can occur through the concerted reaction and the energy barrier of HCl
      elimination changes from 167.4 to 243.3 kJ/mol; allyl group can obviously reduce
      the activation energy of HCl elimination, and the branched-chain can lower the
      energy barrier of HCl elimination at the carbon sites near the branch chain; a
      free radical is more easily converted into aromatic compound through a series of
      isomerizations, cyclization and dehydrogenation; the conjugated polyene could be
      decomposed in parallel reaction channels: one is the evolution of aromatics,
      another is the formation of small molecule products. The above analysis is
      consistent with previous experimental results and analysis.

PMID- 29576512
TI  - What gets measured gets managed: A new method of measuring household food waste.
AB  - The quantification of household food waste is an essential part of setting
      policies and waste reduction goals, but it is very difficult to estimate. Current
      methods include either direct measurements (physical waste surveys) or
      measurements based on self-reports (diaries, interviews, and questionnaires). The
      main limitation of the first method is that it cannot always trace the waste
      source, i.e., an individual household, whereas the second method lacks
      objectivity. This article presents a new measurement method that offers a
      solution to these challenges by measuring daily produced food waste at the
      household level. This method is based on four main principles: (1) capturing
      waste as it enters the stream, (2) collecting waste samples at the doorstep, (3)
      using the individual household as the sampling unit, and (4) collecting and
      sorting waste daily. We tested the feasibility of the new method with an
      empirical study of 192 households, measuring the actual amounts of food waste
      from households as well as its composition. Household food waste accounted for
      45% of total waste (573 g/day per capita), of which 54% was identified as
      avoidable. Approximately two thirds of avoidable waste consisted of vegetables
      and fruit. These results are similar to previous findings from waste surveys, yet
      the new method showed a higher level of accuracy. The feasibility test suggests
      that the proposed method provides a practical tool for policy makers for setting
      policy based on reliable empirical data and monitoring the effectiveness of
      different policies over time.

PMID- 29576513
TI  - Areas on which to focus when seeking to reduce the greenhouse gas emissions of
      commercial waste management. A case study of a hypermarket, Finland.
AB  - This study focuses on commercial waste, which has received less attention than
      household waste in regards to greenhouse gas emission research. First, the global
      warming potential (GWP) of commercial waste management was calculated. Second,
      the impacts of different waste fractions and the processes of waste management
      were recognised. Third, the key areas on which to focus when aiming to reduce the
      greenhouse gas emissions of commercial waste management were determined. This
      study was conducted on the waste generated by a real hypermarket in South-East
      Finland and included eight different waste fractions. The waste treatment plants
      were selected based on the actual situation. Three different scenarios were
      employed to evaluate the environmental impact of managing mixed waste:
      landfilling, combustion and more accurate source separation. The GaBi software
      and impact assessment methodology CML 2001 were used to perform a life cycle
      assessment of the environmental impacts associated with the waste management. The
      results indicated that the total GWP of commercial waste management could be
      reduced by 93% by directing the mixed waste to combustion instead of landfill. A
      further 5% GWP reduction could be achieved by more accurate source separation of
      the mixed waste. Utilisation of energy waste had the most significant influence
      (41-52%) on the total GWP (-880 to -860 kgCO2-eq./t), followed by landfilling of
      mixed waste (influence 15-23% on the total GWP, 430 kgCO2-eq./t), recycling
      polyethylene (PE) plastic (influence 18-21% on the total GWP, -1800 kgCO2-eq./t)
      and recycling cardboard (influence 11-13% on the total GWP, 51 kgCO2-eq./t). A
      key focus should be placed on treatment processes and substitutions, especially
      in terms of substitutions of energy waste and PE plastic. This study also
      clarified the importance of sorting PE plastic, even though the share of this
      waste fraction was not substantial. The results of this paper were compared to
      those of previous studies. The output of this analysis indicated that the total
      GWP can be significantly reduced by identifying an alternative recycling or
      incineration location for cardboard where it is used to substitute virgin
      material or replace fossil fuels respectively. In conclusion, it is essential to
      note that waste management companies have a notable influence on the emissions of
      commercial waste management because they choose the places at which the waste
      fractions are treated and utilised.

PMID- 29576514
TI  - Toward zero waste events: Reducing contamination in waste streams with volunteer
      assistance.
AB  - Public festivals and events generate a tremendous amount of waste, especially
      when they involve food and drink. To reduce contamination across waste streams,
      we evaluated three types of interventions at a public event. In a randomized
      control trial, we examined the impact of volunteer staff assistance, bin tops,
      and sample 3D items with bin tops, on the amount of contamination and the weight
      of the organics, recyclable containers, paper, and garbage bins at a public
      event. The event was the annual Apple Festival held at the University of British
      Columbia, which was attended by around 10,000 visitors. We found that
      contamination was the lowest in the volunteer staff condition among all
      conditions. Specifically, volunteer staff reduced contamination by 96.1% on
      average in the organics bin, 96.9% in the recyclable containers bin, 97.0% in the
      paper bin, and 84.9% in the garbage bin. Our interventions did not influence the
      weight of the materials in the bins. This finding highlights the impact of
      volunteers on reducing contamination in waste streams at events, and provides
      suggestions and implications for waste management for event organizers to
      minimize contamination in all waste streams to achieve zero waste goals.

PMID- 29576515
TI  - Pyrolysis of polystyrene waste in the presence of activated carbon in
      conventional and microwave heating using modified thermocouple.
AB  - Pyrolysis process was experimented using two types of heating source, namely
      conventional and microwave. Polystyrene (PS) plastic waste was used as feedstock
      in a batch reactor for both the conventional (slow pyrolysis) and microwave
      pyrolysis. The effect of activated carbon to polystyrene ratio on (i) yield of
      oil, gas and residues (ii) reaction temperature (iii) reaction time were studied.
      Quality of oil from pyrolysis of polystyrene were assessed for the possible
      applicability in fuel production. Microwave power of 450 W and polymer to
      activated carbon ratio of 10:1, resulted in the highest oil yield of 93.04 wt.%
      with a higher heating value of 45 MJ kg-1 and a kinematic viscosity of 2.7 cSt.
      Microwave heating when compared to conventional heating method, exhibits a
      reaction temperature and time of 330  degrees C in 5.5 min, whereas in
      conventional heating system it was 418  degrees C in 60 min. The gas
      chromatography-mass spectrometry analysis of liquid oil from microwave pyrolysis
      predominantly yields alkenes of 8.44 wt.%, alpha-methyl styrene 0.96 wt.%,
      condensed ring aromatics 23.21 wt.% and benzene derivatives 26.77 wt.% when the
      polystyrene to activated carbon ratio was 10:1. Significant factor of using
      microwave heating is the amount of energy converted (kWh) is lesser than
      conventional heating.

PMID- 29576505
TI  - Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a
      double-blind, randomised, phase 3 study.
AB  - BACKGROUND: No treatment has consistently shown efficacy in slowing disability
      progression in patients with secondary progressive multiple sclerosis (SPMS). We
      assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P)
      receptor1,5 modulator, on disability progression in patients with SPMS. METHODS:
      This event-driven and exposure-driven, double-blind, phase 3 trial was done at
      292 hospital clinics and specialised multiple sclerosis centres in 31 countries.
      Using interactive response technology to assign numbers linked to treatment arms,
      patients (age 18-60 years) with SPMS and an Expanded Disability Status Scale
      score of 3.0-6.5 were randomly assigned (2:1) to once daily oral siponimod 2 mg
      or placebo for up to 3 years or until the occurrence of a prespecified number of
      confirmed disability progression (CDP) events. The primary endpoint was time to 3
      month CDP. Efficacy was assessed for the full analysis set (ie, all randomly
      assigned and treated patients); safety was assessed for the safety set. This
      trial is registered with ClinicalTrials.gov, number NCT01665144. FINDINGS: 1651
      patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to
      the siponimod group, and 546 to the placebo group). One patient did not sign the
      consent form, and five patients did not receive study drug, all of whom were in
      the siponimod group. 1645 patients were included in the analyses (1099 in the
      siponimod group and 546 in the placebo). At baseline, the mean time since first
      multiple sclerosis symptoms was 16.8 years (SD 8.3), and the mean time since
      conversion to SPMS was 3.8 years (SD 3.5); 1055 (64%) patients had not relapsed
      in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903
      (82%) patients receiving siponimod and 424 (78%) patients receiving placebo
      completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%)
      of 545 patients receiving placebo had 3-month CDP (hazard ratio 0.79, 95% CI 0.65
      0.95; relative risk reduction 21%; p=0.013). Adverse events occurred in 975 (89%)
      of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving
      placebo; serious adverse events were reported for 197 (18%) patients in the
      siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia,
      increased liver transaminase concentration, bradycardia and bradyarrhythmia at
      treatment initiation, macular oedema, hypertension, varicella zoster
      reactivation, and convulsions occurred more frequently with siponimod than with
      placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies
      of infections, malignancies, and fatalities did not differ between groups.
      INTERPRETATION: Siponimod reduced the risk of disability progression with a
      safety profile similar to that of other S1P modulators and is likely to be a
      useful treatment for SPMS. FUNDING: Novartis Pharma AG.

PMID- 29576516
TI  - Contagion! The BBC Four Pandemic - The model behind the documentary.
AB  - To mark the centenary of the 1918 influenza pandemic, the broadcasting network
      BBC have put together a 75-min documentary called 'Contagion! The BBC Four
      Pandemic'. Central to the documentary is a nationwide citizen science experiment,
      during which volunteers in the United Kingdom could download and use a custom
      mobile phone app called BBC Pandemic, and contribute their movement and contact
      data for a day. As the 'maths team', we were asked to use the data from the app
      to build and run a model of how a pandemic would spread in the UK. The headline
      results are presented in the TV programme. Here, we document in detail how the
      model works, and how we shaped it according the incredibly rich data coming from
      the BBC Pandemic app. We have barely scratched the depth of the volunteer data
      available from the app. The work presented in this article had the sole purpose
      of generating a single detailed simulation of a pandemic influenza-like outbreak
      in the UK. When the BBC Pandemic app has completed its collection period, the
      vast dataset will be made available to the scientific community (expected early
      2019). It will take much more time and input from a broad range of researchers to
      fully exploit all that this dataset has to offer. But here at least we were able
      to harness some of the power of the BBC Pandemic data to contribute something
      which we hope will capture the interest and engagement of a broad audience.

PMID- 29576517
TI  - Transmission dynamics of influenza in two major cities of Uganda.
AB  - In this paper, we report the epidemic characteristics of the three co-circulating
      influenza viruses (i.e., A/H1N1, A/H3N2, and B) in two tropical African cities
      Kampala and Entebbe, Uganda-over an eight-year period (2008-2015). Using wavelet
      methods, we show that influenza epidemics recurred annually during the study
      period. In most months, two or more influenza viruses co-circulated at the same
      time. However, the epidemic timing differed by influenza (sub)type. Influenza
      A/H3N2 caused epidemics approximately every 2 years in both cities and tended to
      alternate with A/H1N1 or B. Influenza A/H1N1 and B produced smaller but more
      frequent epidemics and biennial epidemics of these two viruses tended to be
      synchronous. In addition, epidemics of A/H3N2 were more synchronized in the two
      cities (located ca.37 km apart) than that of A/H1N1 or influenza B.

PMID- 29576518
TI  - A critical review on anaerobic digestion of microalgae and macroalgae and co
      digestion of biomass for enhanced methane generation.
AB  - Biogas production using algal resources has been widely studied as a green and
      alternative renewable technology. This review provides an extended overview of
      recent advances in biomethane production via direct anaerobic digestion (AD) of
      microalgae, macroalgae and co-digestion mechanism on biomethane production and
      future challenges and prospects for its scaled-up applications. The effects of
      pretreatment in the preparation of algal feedstock for methane generation are
      discussed briefly. The role of different operational and environmental parameters
      for instance pH, temperature, nutrients, organic loading rate (OLR) and hydraulic
      retention time (HRT) on sustainable methane generation are also reviewed.
      Finally, an outlook on the possible options towards the scale up and enhancement
      strategies has been provided. This review could encourage further studies in this
      area, to intend and operate continuous mode by designing stable and reliable
      bioreactor systems and to analyze the possibilities and potential of co-digestion
      for the promotion of algal-biomethane technology.

PMID- 29576519
TI  - Percutaneous closure of patent foramen ovale vs. medical treatment for patients
      with history of cryptogenic stroke: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Patients with history of cryptogenic stroke are more likely to have a
      patent foramen ovale (PFO) and should be managed with antithrombotic agents,
      while the alternative option is percutaneous closure of PFOs. Our aim was to
      perform a meta-analysis of randomized controlled trials (RCTs) comparing
      percutaneous closure vs. medical treatment for patients with PFO and prior
      cryptogenic stroke. METHODS: Medline, Scopus and Cochrane databases were
      reviewed. A random-effect model meta-analysis was used and I-square was utilized
      to assess the heterogeneity. New ischemic stroke was defined as the primary
      endpoint. A sensitivity analysis was performed for Amplatzer device. Subgroup
      analyses were performed for different patient and PFO characteristics for the
      composite endpoints as defined by the included RCTs. RESULTS: In total of 3440
      patients were included in this meta-analysis. Closure devices were superior to
      medical therapy for prevention of recurrent ischemic strokes (HR = 0.29; CI: 0.02
      0.56), but were associated with increased risk of new onset of atrial
      fibrillation (AF) and atrial flutter (RR = 4.67; CI: 2.22-9.81). However, in the
      sensitivity analysis for Amplatzer device, there was no difference between the
      two groups in new onset of atrial arrhythmias. Closure devices were superior
      across all different subgroups when compared to medical treatment with the
      exception of patients with a small shunt. CONCLUSION: This meta-analysis shows
      that closure devices for patients with PFO and history of cryptogenic stroke can
      significantly decrease the risk of a new ischemic stroke. The use of Amplatzer
      device was not associated with increased risk of newly diagnosed atrial
      arrhythmias.

PMID- 29576520
TI  - Allergic recurrent coronary stent thrombosis: A mini-review of Kounis syndrome.
AB  - Kounis syndrome (KS) consists of an association between hypersensitivity
      reactions triggered by various environmental and pharmacological factors and
      acute coronary syndromes. Blood supply may be compromised by either vasospasm
      (type I), native plaque destabilization (type II) or stent thrombosis (type III).
      Although the prognosis is generally favorable, treatment should include
      aggressive anti-thrombotic and anti-allergic therapies. A case compatible with
      type III KS, manifested as a macular rash followed by two episodes of stent
      thrombosis after primary angioplasty (PCI) of the right coronary artery is
      presented, and complemented by a review on the topic.

PMID- 29576521
TI  - Relationship between serum levels of oxidative stress and metabolic syndrome
      components.
AB  - AIMS: This study aimed to investigate the relationship between the total
      antioxidant capacity (TAC) and Malondialdehyde (MDA) with number of metabolic
      syndrome (Mets) components on the personnel working in Shahroud University of
      Medical Sciences. METHODS: This cross-sectional study was conducted on 167
      personnel aged 30-60 years old. ATP III criteria were used to diagnose patients
      with MetS. Oxidative stress indicators were measured. The data was analyzed via
      one-way ANOVA, and Pearson and Spearman correlation coefficients. RESULTS: The
      result showed that TAC had a significant positive correlation with HDL and a
      significant negative correlation with abdominal obesity. In addition, there was a
      significant positive association between the level of MDA and age, BMI, abdominal
      obesity, diastolic blood pressure, triglycerides, and LDL; however, it had a
      negative significant correlation with HDL. CONCLUSIONS: The measurement of TAC
      and MDA biomarkers can increase the early diagnosis of patients at risk of
      developing Mets.

PMID- 29576522
TI  - Dietary pattern in pregnancy and risk of gestational diabetes mellitus (GDM).
AB  - AIM: Among the most common metabolic disorders during pregnancy is gestational
      diabetes mellitus (GDM). This research was conducted to examine the dietary
      pattern in women with GDM. MATERIAL AND METHODS: In this case-study, 204 pregnant
      women (104 cases and 100 control women) were chosen through convenient sampling
      and random sampling. The subjects' food intakes were assessed using semi
      quantitative food frequency questionnaire, while their activities evaluated by
      physical activity questionnaire. Anthropometric indices were measured based on
      standard instructions, and the body mass index was calculated. The dietary
      patterns were determined using principal component analysis and its relationship
      with preeclampsia was tested using logistic regression method. RESULTS: Unhealthy
      and healthy dietary patterns were found among the pregnant women. In the
      unhealthy group, after modifying the effect of confounding variables, a
      significant relationship was observed between dietary pattern and having
      gestational diabetes (OR = 2.838,95% CI:1.039-7.751). In the healthy group, on
      the other hand, the people in the fourth quartile had 149% and 184% higher chance
      not to catch gestational diabetes before and after modification with confounders,
      respectively (OR = 0.284,95% CI:0.096-0.838), when compared with people in the
      first quartile. CONCLUSION: The findings indicated that selection of foods
      including fruits, vegetables, low-fat dairies, etc. as healthy dietary pattern is
      associated with diminished risk of GDM among pregnant women. Determining healthy
      dietary pattern during pregnancy, considering the foods consumed among pregnant
      women, as a useful and practical guide during this period can be publicized for
      training and nutritional interventions.

PMID- 29576523
TI  - Predictors of metformin failure in gestational diabetes mellitus (GDM).
AB  - INTRODUCTION AND OBJECTIVE: The role of metformin in gestational diabetes
      mellitus (GDM) is also increasing. However, almost half of metformin-treated
      women required additional insulin. Therefore, identifying the characteristics of
      these women may help define optimal therapeutic strategy. METHODS: This is a
      retrospective cohort study done in a District General Hospital, UK. GDM was
      diagnosed by 75 g OGTT test between 24 and 28 weeks of gestation with fasting
      levels of >=6.1 mmol/l and/or 2 h postprandial (PP) level of >=7.8 mmol/l.
      Logistic regression and receiver operator curves (ROC) were performed to identify
      the predictors of metformin failure. RESULTS: Out of 228 women with GDM included,
      46/228 (20.2%) and 151/228 (66.2%) received insulin and metformin as first-line
      medication respectively. Among the metformin-treated, 13 stopped treatment and
      were excluded from analysis. Of the included 138 metformin-treated women, 77
      (55.8%) required supplementary insulin (metformin failure). Metformin failure
      group had higher maternal age and fasting glucose level at OGTT, HbA1c at OGTT
      and earlier gestational age (GA) at medication initiation. Metformin failure was
      predicted if fasting OGTT level >4.8 mmol/l (69% sensitivity and 62%
      specificity). If the fasting levels of IADPSG (International Association of
      Diabetes and Pregnancy Study Groups) criteria and NICE (National Institute of
      Health and Care Excellence) were used, the positive predictive value was 78% and
      77% respectively. CONCLUSION: As women with higher fasting glucose levels have
      higher chance of necessitating insulin in later pregnancies, appropriate addition
      of insulin at metformin initiation for these women could help better glycaemic
      control throughout pregnancy.

PMID- 29576525
TI  - Reproducibility of the American Association for the Surgery of Trauma scaling for
      renal injury: Methodological issue to avoid misinterpretation.

PMID- 29576524
TI  - Association between vitamin D status and metabolic syndrome risk factors.
AB  - BACKGROUND: The concern with the incidence of chronic-degenerative diseases is
      increasing worldwide, and many studies have shown that insufficiency of vitamin D
      (VD) can be linked to several metabolic disorders. AIMS: Thus, the objective of
      this study was to evaluate the association of the metabolic syndrome risk
      factors, atherogenic indices and VD in a group of patients attended at a
      Cardiology Center. METHODS: For this study, we invited 200 patients of both sexes
      attended in a Cardiology Center (Medical School of Marilia - Sao Paulo - Brazil).
      Most were female (n = 111) and aged between 41 and 70 years (from march to
      august, 2017). RESULTS: Our results showed that only 20.0% of the patients
      presented normal levels of VD. Patients with altered values for this vitamin
      presented significantly higher values for glycemia, HbA1c, Total cholesterol, LDL
      c, triglycerides, Castelli Index I, Castelli Index II, Body Mass Index, waist
      circumference, non-HDL-c and the estimative of the size of the LDL-c particle.
      Vitamin D correlated negatively with glycemia, HbA1C, triglycerides, atherogenic
      indices, Body Mass Index, and blood pressure. Multiple Regression Model showed
      that for an individual to maintain metabolic parameters, at least at borderline
      values, the levels of VD should be 37.64 that is not in accordance with the
      reference values. CONCLUSIONS: These results showed a remarkable prevalence of
      low concentrations of Vitamin D in patients with cardiovascular risk factors.

PMID- 29576526
TI  - Systematic Characterization of Stress-Induced RNA Granulation.
AB  - Upon stress, cytoplasmic mRNA is sequestered to insoluble ribonucleoprotein (RNP)
      granules, such as the stress granule (SG). Partially due to the belief that
      translationally suppressed mRNAs are recruited to SGs in bulk, stress-induced
      dynamic redistribution of mRNA has not been thoroughly characterized. Here, we
      report that endoplasmic reticulum (ER) stress targets only a small subset of
      translationally suppressed mRNAs into the insoluble RNP granule fraction (RG).
      This subset, characterized by extended length and adenylate-uridylate (AU)-rich
      motifs, is highly enriched with genes critical for cell survival and
      proliferation. This pattern of RG targeting was conserved for two other stress
      types, heat shock and arsenite toxicity, which induce distinct responses in the
      total cytoplasmic transcriptome. Nevertheless, stress-specific RG-targeting
      motifs, such as guanylate-cytidylate (GC)-rich motifs in heat shock, were also
      identified. Previously underappreciated, transcriptome profiling in the RG may
      contribute to understanding human diseases associated with RNP dysfunction, such
      as cancer and neurodegeneration.

PMID- 29576528
TI  - ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome
      Stability.
AB  - Deubiquitylating enzymes (DUBs) enhance the dynamics of the versatile ubiquitin
      (Ub) code by reversing and regulating cellular ubiquitylation processes at
      multiple levels. Here we discovered that the uncharacterized human protein ZUFSP
      (zinc finger with UFM1-specific peptidase domain protein/C6orf113/ZUP1), which
      has been annotated as a potentially inactive UFM1 protease, and its fission yeast
      homolog Mug105 define a previously unrecognized class of evolutionarily conserved
      cysteine protease DUBs. Human ZUFSP selectively interacts with and cleaves long
      K63-linked poly-Ub chains by means of tandem Ub-binding domains, whereas it
      displays poor activity toward mono- or di-Ub substrates. In cells, ZUFSP is
      recruited to and regulates K63-Ub conjugates at genotoxic stress sites, promoting
      chromosome stability upon replication stress in a manner dependent on its
      catalytic activity. Our findings establish ZUFSP as a new type of linkage
      selective cysteine peptidase DUB with a role in genome maintenance pathways.

PMID- 29576527
TI  - Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class
      Important for Genome Stability.
AB  - Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling.
      Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113.
      High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal
      several distinctive features of ubiquitin recognition and catalysis. Our analyses
      reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us
      to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic
      domain does not cleave polyubiquitin. We identify two ubiquitin binding domains
      in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an
      atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both
      domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin.
      We show that ZUFSP localizes to DNA lesions, where it plays an important role in
      genome stability pathways, functioning to prevent spontaneous DNA damage and also
      promote cellular survival in response to exogenous DNA damage.

PMID- 29576529
TI  - Sequential Enhancer Sequestration Dysregulates Recombination Center Formation at
      the IgH Locus.
AB  - Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that
      juxtapose a variable (VH), a diversity (DH), and a joining (JH) gene segment.
      Here, we report that in the absence of intergenic control region 1 (IGCR1), the
      intronic enhancer (EMU) associates with the next available CTCF binding site
      located close to VH81X via putative heterotypic interactions involving YY1 and
      CTCF. The alternate EMU/VH81X loop leads to formation of a distorted
      recombination center and altered DH rearrangements and disrupts chromosome
      conformation that favors distal VH recombination. Cumulatively, these features
      drive highly skewed, EMU-dependent recombination of VH81X. Sequential deletion of
      CTCF binding regions on IGCR1-deleted alleles suggests that they influence
      recombination of single proximal VH gene segments. Our observations demonstrate
      that EMU interacts differently with IGCR1- or VH-associated CTCF binding sites
      and thereby identify distinct roles for insulator-like elements in directing
      enhancer activity.

PMID- 29576530
TI  - Latest Evidence on the Impact of Smoking, Sports, and Sexual Activity as
      Modifiable Lifestyle Risk Factors for Prostate Cancer Incidence, Recurrence, and
      Progression: A Systematic Review of the Literature by the European Association of
      Urology Section of Oncological Urology (ESOU).
AB  - CONTEXT: Smoking, sexual activity, and physical activity (PA) are discussed as
      modifiable lifestyle factors associated with prostate cancer (PCa) development
      and progression. OBJECTIVE: To evaluate the available evidence concerning the
      association of smoking, sexual activity, and sports and exercise on PCa risk,
      treatment outcome, progression, and cancer-specific mortality. EVIDENCE
      ACQUISITION: A systematic review of studies published between 2007 and 2017 using
      MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Web of
      Science databases according to the Preferred Reporting Items for Systematic
      Reviews and Meta-Analysis statement criteria was conducted. EVIDENCE SYNTHESIS:
      While data concerning the impact of smoking on PCa development remain
      conflicting, there is robust evidence that smoking is associated with aggressive
      tumor features and worse cancer-related outcome, which seems to be maintained for
      10 yr after smoking cessation. Less convincing and limited evidence exists for
      the association of sexual activity with PCa risk. The findings related to PA and
      PCa support the inference that exercise might be a useful factor in the
      prevention of PCa and tumor progression, while it is not finally proved under
      which specific conditions PA might be protective against disease development.
      CONCLUSIONS: Smoking is associated with aggressive tumor features and worse
      cancer-related prognosis; as this negative impact seems to be maintained for 10yr
      after smoking cessation, urologists should advise men to quit smoking latest at
      PCa diagnosis to improve their prognosis. As several studies indicate a positive
      impact of exercise on tumor development, progression, and treatment outcome, it
      is certainly reasonable to advocate an active lifestyle. Least convincing
      evidence is available for the interaction of sexual activity and PCa, and well
      conducted and longitudinal studies are clearly necessary to evaluate whether the
      suggested associations between PCa risk and sexual behavior are real or spurious.
      PATIENT SUMMARY: In this systematic review, we looked at the impact of smoking,
      sexual activity, and sports and exercise on prostate cancer risk and outcome
      after treatment. While the evidence for sexual activity is not overall clear, we
      found that smoking might lead to more aggressive cancers and result in worse
      treatment outcome. Physical activity might prevent prostate cancer and improve
      cancer-related outcomes as well. Hence, it is certainly reasonable to advocate an
      active lifestyle and advise men to quit smoking.

PMID- 29576531
TI  - Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in
      Glioblastoma-Patient-Derived Cells.
AB  - Transition metals are essential, but deregulation of their metabolism causes
      toxicity. Here, we report that the compound NSC319726 binds copper to induce
      oxidative stress and arrest glioblastoma-patient-derived cells at picomolar
      concentrations. Pharmacogenomic analysis suggested that NSC319726 and 65 other
      structural analogs exhibit lethality through metal binding. Although NSC319726
      has been reported to function as a zinc ionophore, we report here that this
      compound binds to copper to arrest cell growth. We generated and validated
      pharmacogenomic predictions: copper toxicity was substantially inhibited by
      hypoxia, through an hypoxia-inducible-factor-1alpha-dependent pathway; copper
      bound NSC319726 induced the generation of reactive oxygen species and depletion
      of deoxyribosyl purines, resulting in cell-cycle arrest. These results suggest
      that metal-induced DNA damage may be a consequence of exposure to some
      xenobiotics, therapeutic agents, as well as other causes of copper dysregulation,
      and reveal a potent mechanism for targeting glioblastomas.

PMID- 29576532
TI  - Structural Insights into the Forward and Reverse Enzymatic Reactions in Human
      Adenine Phosphoribosyltransferase.
AB  - Phosphoribosyltransferases catalyze the displacement of a PRPP alpha-1'
      pyrophosphate to a nitrogen-containing nucleobase. How they control the balance
      of substrates/products binding and activities is poorly understood. Here, we
      investigated the human adenine phosphoribosyltransferase (hAPRT) that produces
      AMP in the purine salvage pathway. We show that a single oxygen atom from the
      Tyr105 side chain is responsible for selecting the active conformation of the 12
      amino acid long catalytic loop. Using in vitro, cellular, and in crystallo
      approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic
      activity efficiencies of the forward and reverse reactions. Together, our results
      reveal an evolutionary pressure on the strictly conserved Tyr105 and on the
      dynamic motion of the flexible loop in phosphoribosyltransferases that is
      essential for purine biosynthesis in cells. These data also provide the framework
      for designing novel adenine derivatives that could modulate, through hAPRT,
      diseases-involved cellular pathways.

PMID- 29576534
TI  - The Homeostatic Force of Ghrelin.
AB  - Ghrelin, a gastric-derived acylated peptide, regulates energy homeostasis by
      transmitting information about peripheral nutritional status to the brain, and is
      essential for protecting organisms against famine. Ghrelin operates brain
      circuits to regulate homeostatic and hedonic feeding. Recent research advances
      have shed new light on ghrelin's multifaceted roles in cellular homeostasis,
      which could maintain the internal environment and overcome metaflammation in
      metabolic organs. Here, we highlight our current understanding of the regulatory
      mechanisms of the ghrelin system in energy metabolism and cellular homeostasis
      and its clinical trials. Future studies of ghrelin will further elucidate how the
      stomach regulates systemic homeostasis.

PMID- 29576533
TI  - Dual Modifications of alpha-Galactosylceramide Synergize to Promote Activation of
      Human Invariant Natural Killer T Cells and Stimulate Anti-tumor Immunity.
AB  - Glycosylceramides that activate CD1d-restricted invariant natural killer T (iNKT)
      cells have potential therapeutic applications for augmenting immune responses
      against cancer and infections. Previous studies using mouse models identified
      sphinganine variants of alpha-galactosylceramide as promising iNKT cell
      activators that stimulate cytokine responses with a strongly proinflammatory
      bias. However, the activities of sphinganine variants in mice have generally not
      translated well to studies of human iNKT cell responses. Here, we show that
      strongly proinflammatory and anti-tumor iNKT cell responses were achieved in mice
      by a variant of alpha-galactosylceramide that combines a sphinganine base with a
      hydrocinnamoyl ester on C6" of the sugar. Importantly, the activities observed
      with this variant were largely preserved for human iNKT cell responses.
      Structural and in silico modeling studies provided a mechanistic basis for these
      findings and suggested basic principles for capturing useful properties of
      sphinganine analogs of synthetic iNKT cell activators in the design of
      immunotherapeutic agents.

PMID- 29576535
TI  - Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction
      Support the Rate of Living and Oxidative Damage Theories of Aging.
AB  - Calorie restriction (CR) is a dietary intervention with potential benefits for
      healthspan improvement and lifespan extension. In 53 (34 CR and 19 control) non
      obese adults, we tested the hypothesis that energy expenditure (EE) and its
      endocrine mediators are reduced with a CR diet over 2 years. Approximately 15% CR
      was achieved over 2 years, resulting in an average 8.7 kg weight loss, whereas
      controls gained 1.8 kg. In the CR group, EE measured over 24 hr or during sleep
      was approximately 80-120 kcal/day lower than expected on the basis of weight
      loss, indicating sustained metabolic adaptation over 2 years. This metabolic
      adaptation was accompanied by significantly reduced thyroid axis activity and
      reactive oxygen species (F2-isoprostane) production. Findings from this 2-year CR
      trial in healthy, non-obese humans provide new evidence of persistent metabolic
      slowing accompanied by reduced oxidative stress, which supports the rate of
      living and oxidative damage theories of mammalian aging.

PMID- 29576536
TI  - gamma-Secretase Inhibition Lowers Plasma Triglyceride-Rich Lipoproteins by
      Stabilizing the LDL Receptor.
AB  - Excess plasma triglycerides (TGs) are a key component of obesity-induced
      metabolic syndrome. We have shown that gamma-secretase inhibitor (GSI) treatment
      improves glucose tolerance due to inhibition of hepatic Notch signaling but found
      additional Notch-independent reduction of plasma TG-rich lipoproteins (TRLs) in
      GSI-treated, as well as hepatocyte-specific, gamma-secretase knockout (L-Ncst)
      mice, which suggested a primary effect on hepatocyte TRL uptake. Indeed, we found
      increased VLDL and LDL particle uptake in L-Ncst hepatocytes and Ncst-deficient
      hepatoma cells, in part through reduced gamma-secretase-mediated low-density
      lipoprotein receptor (LDLR) cleavage and degradation. To exploit this novel
      finding, we generated a liver-selective Nicastrin ASO, which recapitulated
      glucose and lipid improvements of L-Ncst mice, with increased levels of
      hepatocyte LDLR. Collectively, these results identify the role of hepatic gamma
      secretase to regulate LDLR and suggest that liver-specific GSIs may
      simultaneously improve multiple aspects of the metabolic syndrome.

PMID- 29576537
TI  - Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent
      Stem Cells.
AB  - Retinal ganglion cells (RGCs) are the projection neurons of the retina and
      transmit visual information to postsynaptic targets in the brain. While this
      function is shared among nearly all RGCs, this class of cell is remarkably
      diverse, comprised of multiple subtypes. Previous efforts have identified
      numerous RGC subtypes in animal models, but less attention has been paid to human
      RGCs. Thus, efforts of this study examined the diversity of RGCs differentiated
      from human pluripotent stem cells (hPSCs) and characterized defined subtypes
      through the expression of subtype-specific markers. Further investigation of
      these subtypes was achieved using single-cell transcriptomics, confirming the
      combinatorial expression of molecular markers associated with these subtypes, and
      also provided insight into more subtype-specific markers. Thus, the results of
      this study describe the derivation of RGC subtypes from hPSCs and will support
      the future exploration of phenotypic and functional diversity within human RGCs.

PMID- 29576538
TI  - A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem
      Cells.
AB  - The ten-eleven translocation (TET) proteins are well known for their role in
      maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate
      that, jointly, TET1 and TET2 also safeguard the self-renewal potential of
      trophoblast stem cells (TSCs) and have partially redundant roles in maintaining
      the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show
      that this is achieved by binding to critical epithelial genes, notably E
      cadherin, which becomes hyper-methylated and downregulated in the absence of
      TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is
      accompanied by centrosome duplication and separation defects. Moreover, we
      identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as
      facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs
      are prone to undergo endoreduplicative cell cycles leading to the formation of
      polyploid trophoblast giant cells. Taken together, our data reveal essential
      functions of TET proteins in the trophoblast lineage.

PMID- 29576539
TI  - A Humanized Mouse Model Generated Using Surplus Neonatal Tissue.
AB  - Here, we describe the NeoThy humanized mouse model created using non-fetal human
      tissue sources, cryopreserved neonatal thymus and umbilical cord blood
      hematopoietic stem cells (HSCs). Conventional humanized mouse models are made by
      engrafting human fetal thymus and HSCs into immunocompromised mice. These mice
      harbor functional human T cells that have matured in the presence of human self
      peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more
      abundant and developmentally mature and allows for creation of up to ~50-fold
      more mice per donor compared with fetal tissue models. The NeoThy has equivalent
      frequencies of engrafted human immune cells compared with fetal tissue humanized
      mice and exhibits T cell function in assays of ex vivo cell proliferation,
      interferon gamma secretion, and in vivo graft infiltration. The NeoThy model may
      provide significant advantages for induced pluripotent stem cell immunogenicity
      studies, while bypassing the requirement for fetal tissue.

PMID- 29576541
TI  - Cold stress tolerance in rice: physiological changes, molecular mechanism, and
      future prospects.
AB  - Low temperature is a major factor affecting rice geographical distribution
      growth, development, and productivity. Cold stress mediates a series of
      physiological and metabolite changes, such as alterations in chlorophyll
      fluorescence, electrolyte leakage, reactive oxygen species (ROS), malondialdehyde
      (MAD), sucrose, lipid peroxides, proline, and other metabolites, plant endogenous
      hormones abscisic acid (ABA) and gibberellin (GA) also changes. In this review,
      we summarize the recent research progress on physiological and metabolic changes
      under low temperature, cold stress related loci and QTL reported by map-based
      cloning and genome-wide association analysis (GWAS), and some molecular
      mechanisms in response to low temperature in rice. We also discuss the future
      prospects on breeding cold tolerance varieties of rice.

PMID- 29576542
TI  - Histone variant H3.3 and its functions in reprogramming.
AB  - Histones are a class of evolutionarily conserved nuclear proteins. Histone
      octamer wrapped by DNA sequence forms the nucleosome, the basic building blocks
      of eukaryotic chromatin. The nucleosomes keep the DNA in a condensed state,
      maintain the integrity of the genome, and ensure proper DNA replication,
      transcription, recombination and repair. Nucleosomes can regulate the biological
      processes of the cell through a number of distinct post-translational
      modifications (PTMs) and turnovers of histone variants. Although the histone H3
      variant H3.3 differs from the canonical histone H3 by only a few amino acids, it
      could be incorporated into distinct chromatin regions by specific chaperones and
      exert diverse functions on the chromatin. Importantly, H3.3 is also an essential
      maternal factor, and plays a key role in cellular reprogramming during
      fertilization and somatic cell nuclear transfer. In this review, we summarize the
      structural properties and enrichment pattern of H3.3, and explore the specific
      chaperones involved in the H3.3-mediated cellular reprogramming. We hope to
      provide some insights on new means to improve the efficiency of somatic cell
      reprogramming and lay the foundation for its potential applications.

PMID- 29576540
TI  - Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance
      Neuronal Development.
AB  - Human stem cell-derived models of development and neurodegenerative diseases are
      challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or
      Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and
      enable co-culture of distinct cell types. Brain microvascular endothelial cells
      (BMECs) share common signaling pathways with neurons early in development, but
      their contribution to human neuronal maturation is largely unknown. To study this
      interaction and influence of microculture, we derived both spinal motor neurons
      and BMECs from human induced pluripotent stem cells and observed increased
      calcium transient function and Chip-specific gene expression in Organ-Chips
      compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular
      neural interaction and specific gene activation that further enhanced neuronal
      function and in vivo-like signatures. The results show that the vascular system
      has specific maturation effects on spinal cord neural tissue, and the use of
      Organ-Chips can move stem cell models closer to an in vivo condition.

PMID- 29576543
TI  - Research progress in sRNAs and functional proteins in epididymosomes.
AB  - The semen quality is a basic and the most important indicator of male
      reproductive health. Mammalian spermatozoa undergo a series of complex structural
      and functional changes in the epididymis to mature and achieve fertilization
      capacity. Sperm cell maturation is mediated by a complex physiological process,
      which is synergistically regulated by a large number of transcription factors,
      hormones and other signaling molecules. In recent years, there is increasing
      evidence supporting the notion that functional proteins and sRNA (small RNAs) in
      epididymosomes participate in sperm maturation and fertilization process. In this
      review, we summarize the biological roles of functional proteins and two major
      sRNAs (tRNAs and miRNAs) in sperm maturation in epididymosomes, and provide some
      theoretical guidance and new ideas for treatments of low fertility, infertility
      and other reproductive diseases in men.

PMID- 29576544
TI  - The genetic background and application of Down syndrome mouse models.
AB  - Down syndrome (DS), trisomy chromosome 21 (Hsa21), is the most common genetic
      disease caused by chromosome aberration in the human genome. Modeling DS in mice
      has been challenging since the orthologs of Hsa21 genes map to separate segments
      of three mouse chromosomes, Mmu16, Mmu17, and Mmu10. Although the early Ts65Dn
      mouse model exhibited various DS phenotypes, the duplicated fragments were
      randomly generated by ionizing radiation and did not include all Hsa21 orthologs.
      In 2004, the successful use of the Cre/LoxP recombination technique in
      chromosomal engineering in the construction of the Ts1Rhr mouse strain solved the
      problem of duplication of specific chromosome segment, resulting in the
      establishment of specific DS mouse models with accurate triplication of
      particular genes and associated phenotypes. In this review, we briefly introduce
      the different DS mouse models and discuss their advantages and limitations by
      focusing on the triplication of Hsa21 orthologs and manifestations of DS
      phenotypes, thereby providing some references for the selection of specific mouse
      models in DS research.

PMID- 29576545
TI  - Research progress in machine learning methods for gene-gene interaction
      detection.
AB  - Complex diseases are results of gene-gene and gene-environment interactions.
      However, the detection of high-dimensional gene-gene interactions is
      computationally challenging. In the last two decades, machine-learning approaches
      have been developed to detect gene-gene interactions with some successes. In this
      review, we summarize the progress in research on machine learning methods, as
      applied to gene-gene interaction detection. It systematically examines the
      principles and limitations of the current machine learning methods used in genome
      wide association studies (GWAS) to detect gene-gene interactions, such as neural
      networks (NN), random forest (RF), support vector machines (SVM) and multifactor
      dimensionality reduction (MDR), and provides some insights on the future research
      directions in the field.

PMID- 29576546
TI  - Co-amplification at lower denaturation temperature-PCR: methodology and
      applications.
AB  - Co-amplification at lower denaturation temperature-polymerase chain reaction
      (COLD-PCR) is a novel form of PCR that selectively denatures and amplifies low
      abundance mutations from mixtures of wild-type and mutation-containing sequences,
      enriching the mutation 10 to 100 folds. Due to the slightly altered melting
      temperature (Tm) of the double-stranded DNA and the formation of the
      mutation/wild-type heteroduplex DNA, COLD-PCR methods are sensitive, specific,
      accurate, cost-effective and easy to maneuver, and can enrich mutations of any
      type and at any position, even unknown mutations within amplicons. COLD-PCR and
      its improved methods are now applied in cancer, microorganisms, prenatal
      screening, animals and plants. They are extremely useful for early diagnosis,
      monitoring the prognosis of disease and the efficiency of the treatment, drug
      selection, prediction of prognosis, plant breeding and etc. In this review, we
      introduce the principles, key techniques, derived methods and applications of
      COLD-PCR.

PMID- 29576547
TI  - Expression specificity and compensation effect of Ash2l-1/Ash2l-2 in mouse
      embryonic stem cells.
AB  - H3K4me3 is an important epigenetic modification that plays a critical role in
      maintaining self-renewal of mouse embryonic stem cells (mESCs). H3K4me3 is
      catalyzed mainly by the mixed lineage leukemia (MLL) methyl-transferase complex.
      ASH2L, a core subunit of the MLL complex, participates in regulating the open
      state of chromatin in mESCs. There are two isoforms of the ASH2L protein: ASH2L-1
      (80 kDa), which only exists in mouse embryonic fibroblasts and ASH2L-2 (65 kDa),
      which is the predominant isoform in mESCs. The roles of Ash2l-1 and Ash2l-2 in
      mESCs have not yet been elucidated. In this study, we established Ash2l-1 -/- and
      Ash2l-2 -/- knockout mESCs using CRISPR/Cas9. Alkaline phosphatase (AP) staining,
      immunofluorescence staining, and qRT-PCR showed that there were no obvious
      differences on the expression level of AP and pluripotent transcription factors
      (Nanog, Oct4, sox2 and Klf4) among Ash2l-1 -/- mESCs, Ash2l-2 -/- mESCs and wild
      type (WT) mESCs. However, analysis of embryoid body (EB) differentiation showed
      that the expression level of Snai2 (ectoderm gene) and Gata4 (endoderm gene) in
      Ash2l-1 -/- EBs was significantly lower than that in WT EBs (P<0.01). Western
      blotting assay revealed that the expression of ASH2L-2 was significantly
      increased (P<0.01) in Ash2l-1 -/- mESCs and vice versa. However, there were no
      obvious differences on the genomic H3K4me3 level among Ash2l-1 -/- mESCs, Ash2l-2
      -/- mESCs and WT mESCs. These results indicate that there exist compensation
      effects between Ash2l-1 and Ash2l-2. Bioinformatic analysis predicted that there
      were three and 16 potential binding sites for pluripotency transcription factors
      located in the promoter of Ash2l-1 and Ash2l-2, respectively. Theses
      transcription factors may mediate the compensation effect between Ash2l-1 and
      Ash2l-2. Collectively, these results indicate that the compensation effects
      between Ash2l-1 and Ash2l-2 may be involved in the maintenance of mESCs
      pluripotency and the regulation of genomic H3K4me3.

PMID- 29576548
TI  - A genetics laboratory class to analyze early and late feather traits of chicken.
AB  - With the implementation of the "Education and Training Program for Outstanding
      Agricultural and Forestry Talents" in our country, our university established the
      "Outstanding Class" for students majoring in the animal science. We also carried
      out a series of educational management and curriculum reforms to cultivate
      students' systematic model of thinking and the ability of technology innovation.
      In this paper, we designed a comprehensive experiment that focused on analyzing
      early and late feather genetic traits of chicken. The students initially observed
      the phenotype of chickens and gradually were led into genetics analysis. We
      introduced the breeding practice, and guided the students to use genetic theories
      to breed chick strains of early and late feather traits. The experiment is not
      only based on the sex-linkage theory and sex determination mechanism, but also
      molecular genetics technologies, such as genomic DNA extraction, amplification,
      enzyme digestion and electrophoresis. Conducting this experiment can enhance
      students' comprehensive analysis ability and professional skills, as well as be
      beneficial to cultivate their scientific research interests and curiosity on
      animal sciences. Thus, we integrated the genetics theories into animal breeding
      practice that meet the requirement of comprehensive applied talents of animal
      science specialty. The teaching ideas and methods described in this paper can be
      applied to other biological experiment teaching practice.

PMID- 29576549
TI  - Incorporation of the delta-subunit into the epithelial sodium channel (ENaC)
      generates protease-resistant ENaCs in Xenopus laevis.
AB  - The epithelial sodium channel (ENaC) is a critical regulator of vertebrate
      electrolyte homeostasis. ENaC is the only constitutively open ion channel in the
      degenerin/ENaC protein family, and its expression, membrane abundance, and open
      probability therefore are tightly controlled. The canonical ENaC is composed of
      three subunits (alpha, beta, and gamma), but a fourth delta-subunit may replace
      alpha and form atypical deltabetagamma-ENaCs. Using Xenopus laevis as a model,
      here we found that mRNAs of the alpha- and delta-subunits are differentially
      expressed in different tissues and that delta-ENaC predominantly is present in
      the urogenital tract. Using whole-cell and single-channel electrophysiology of
      oocytes expressing Xenopus alphabetagamma- or deltabetagamma-ENaC, we demonstrate
      that the presence of the delta-subunit enhances the amount of current generated
      by ENaC due to an increased open probability, but also changes current into a
      transient form. Activity of canonical ENaCs is critically dependent on
      proteolytic processing of the alpha- and gamma-subunits, and immunoblotting with
      epitope-tagged ENaC subunits indicated that, unlike alpha-ENaC, the delta-subunit
      does not undergo proteolytic maturation by the endogenous protease furin.
      Furthermore, currents generated by deltabetagamma-ENaC were insensitive to
      activation by extracellular chymotrypsin, and presence of the delta-subunit
      prevented cleavage of gamma-ENaC at the cell surface. Our findings suggest that
      subunit composition constitutes an additional level of ENaC regulation, and we
      propose that the Xenopus delta-ENaC subunit represents a functional example that
      demonstrates the importance of proteolytic maturation during ENaC evolution.

PMID- 29576551
TI  - Symptoms of Anxiety and Depression in Obese Singaporeans: a Preliminary Study.
AB  - BACKGROUND: Obesity is a major component of metabolic syndrome and an independent
      risk factor for various chronic diseases. It is also closely associated with
      mental illness, and the interaction is complex and multifactorial. This study
      aimed to estimate the prevalence of anxiety and depressive symptoms among obese
      Singaporeans. METHODS: Cross-sectional data of 36 male and 47 female obese
      Singaporeans who had been referred to the weight management clinic of National
      University Hospital, Singapore, between January 2010 and November 2011 were
      collected. Obesity was classified according to criteria of the World Health
      Organization. The extents of anxiety and depressive symptoms were measured using
      the Hospital Anxiety and Depression Scale. RESULTS: In obese Singaporeans
      attending the weight management clinic, the prevalence of anxiety symptoms was
      higher than that of depressive symptoms (28% vs 11%). There was no major
      socioeconomic difference between obese patients with and without anxiety, or with
      and without depressive symptoms. CONCLUSION: In obese Singaporeans, anxiety
      symptoms may be more common than depressive symptoms. Weight management
      programmes should incorporate anxiety management as part of standard treatment.
      Early detection and pharmacological and psychological interventions should be
      implemented.

PMID- 29576550
TI  - Apolipoprotein-defined lipoprotein subclasses, serum apolipoproteins, and carotid
      intima-media thickness in T1D.
AB  - Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and
      apolipoproteins predict vascular events in the general and type 2 diabetes
      populations, but data in T1D are limited. We examined associations of ADLS, serum
      apolipoproteins, and conventional lipids with carotid intima-media thickness
      (IMT) measured contemporaneously and 6 years later in 417 T1D participants [men:
      n = 269, age 42 +/- 6 y (mean +/- SD); women: n = 148, age 39 +/- 8 y] in the
      Epidemiology of Diabetes Interventions and Complications study, the follow-up of
      the Diabetes Control and Complications Trial (DCCT). Date were analyzed by
      multiple linear regression stratified by sex, and adjusted for time-averaged
      hemoglobin A1C, diabetes duration, hypertension, BMI, albuminuria, DCCT
      randomization, smoking, statin treatment, and ultrasound devices. In cross
      sectional analyses, lipoprotein B (Lp-B), Lp-B:C, Lp-B:E+Lp-B:C:E, Apo-A-II, Apo
      B, Apo-C-III-HP (heparin precipitate; i.e., Apo-C-III in Apo-B-containing
      lipoproteins), and Apo-E were positively associated with common and/or internal
      carotid IMT in men, but only Apo-C-III (total) was (positively) associated with
      internal carotid IMT in women. In prospective analyses, Lp-B, Apo-B, and Apo-C
      III-HP were positively associated with common and/or internal carotid IMT in men,
      while Lp-A1:AII and Apo-A1 were inversely associated with internal carotid IMT in
      women. The only significant prospective association between conventional lipids
      and IMT was between triacylglycerols and internal carotid IMT in men. ADLS and
      apolipoprotein concentrations may provide sex-specific biomarkers and suggest
      mechanisms for IMT in people with T1D.

PMID- 29576552
TI  - Frontal Theta Asymmetry as a Biomarker of Depression.
AB  - INTRODUCTION: Electroencephalography (EEG) has been used extensively to study
      affective disorders. Quantitative spectral analysis of an EEG scan has been used
      to assess the biological basis of emotional disorders such as depression as well
      as to investigate biomarkers of affective disorders. Inter-hemispheric
      asymmetries in both baseline and stimulus-evoked frequencies (alpha, beta, theta,
      and delta) are potential biomarkers of depression. The role of frontal alpha
      asymmetry has been established, but other spectral frequencies such as frontal
      theta remain elusive. We compared the hemispheric differences in frontal theta
      power in depressed patients and controls before and during listening to music to
      study the correlation of frontal theta asymmetry with depression. METHODS: To
      determine whether stimulus-evoked frontal theta asymmetry is a biomarker of
      depression, we compared 23 patients with mild depression (based on the Hamilton
      Depression Rating Scale) with 17 age- and sex-matched controls by conducting EEG
      at rest and after listening to Indian classical music. RESULTS: In controls
      without depression, the mean frontal theta power of the left hemisphere and
      frontal theta asymmetry increased significantly during music listening. In
      depressed patients, frontal theta asymmetry was reversed during music listening.
      CONCLUSION: Frontal theta asymmetry is a potential biomarker of depression.

PMID- 29576553
TI  - Self-harm and Suicide Attempts in a Japanese Psychiatric Hospital.
AB  - OBJECTIVE: Self-harm and attempted suicide are risk factors for suicide in
      psychiatric hospital in-patients. This study aimed to analyse the circumstances
      of self-harm and suicide attempts in a Japanese psychiatric hospital so as to
      improve management and care. METHODS: Incident reports of self-harm and suicide
      attempts during a 12.4-year period from November 2000 to March 2013 were
      reviewed. A descriptive analysis was conducted in terms of age, sex, and
      diagnosis of patients, as well as level, ward, situations, and causes of
      incidents. RESULTS: During the study period, 90 cases of self-harm and attempted
      suicide involving 58 patients were reported. The rate of self-harm and suicide
      attempts was 0.05 per 1000 patient-days. The types of selfharm and suicide
      attempts included hanging (n = 25), wrist cutting (n = 19), ingestion of foreign
      objects (n = 17), and others (n = 29). The single case of completed suicide
      involved hanging, in a patient with schizophrenia. Among 55 patients with
      relevant data, the most common clinical diagnosis was mood disorder (41.8%),
      followed by schizophrenia (36.4%). Mood disorder was 3.5 times as prevalent in
      females as in males (14 vs. 4). Fourteen patients with mood disorder (n = 8) or
      schizophrenia (n = 6) were repeatedly involved in 46 of 89 cases of self-harm or
      attempted suicide; 11 were female. One woman with mood disorder attempted suicide
      9 times within the same year. The top 3 management and care factors related to
      self-harm and suicide attempts were failure to adhere to preventive procedures
      (28%), insufficient therapeutic communication (28%), and difficulty in predicting
      suicide (20%). CONCLUSION: Self-harm and suicide attempts at this psychiatric
      hospital occurred at a rate of 0.05 per 1000 patient-days between late 2000 and
      early 2013. Efforts are needed to increase compliance with suicide prevention
      procedures and therapeutic communication, so as to improve management and care of
      psychiatric in-patients and prevent them from committing suicide.

PMID- 29576554
TI  - Electrocardiographic Monitoring of Psychiatric In-patients Taking Antipsychotic
      Medications.
AB  - OBJECTIVE: To assess the adherence to guidelines for electrocardiographic (ECG)
      monitoring in Hong Kong psychiatric in-patients who have been prescribed
      antipsychotic medications. METHODS: In-patients who had been prescribed
      antipsychotic drugs on hospital admission during the baseline audit period of 15
      April 2015 to 16 July 2015 and the re-audit period of 28 January 2016 to 30 April
      2016 were included. Quality improvement interventions were delivered after the
      baseline audit. ECG monitoring adherence was categorised as full adherence (ECG
      before taking antipsychotics), partial adherence (ECG after taking
      antipsychotics), or non-adherence (no ECG during hospital stay). Overall
      compliance was defined as full adherence plus partial adherence. RESULTS: The
      baseline audit and re-audit included 378 and 422 patients, respectively. Overall
      compliance with ECG monitoring increased significantly from the baseline audit to
      re-audit (40.2% vs. 69.9%; p < 0.001). Case-doctors having the grade of resident
      was associated with stronger adherence to ECG monitoring in both audits.
      CONCLUSION: Adherence to ECG monitoring guidelines for in-patients who are
      prescribed antipsychotic drugs is low in Hong Kong, and junior doctors
      (residents) demonstrate stronger adherence than moresenior doctors.

PMID- 29576555
TI  - A systematic experimental study of parameters influencing 131-iodine in vivo
      spectroscopic measurements using age-specific thyroid phantoms.
AB  - In case of nuclear accident, the internal exposure monitoring of the population
      will preferably focus on the detection of 131I in the thyroid by in vivo
      monitoring. In most cases, the calibration of in vivo monitoring is performed
      with an adult thyroid phantom, which raises doubts regarding the relevance of
      child exposure assessment. In this study, the influence on the calibration of the
      thyroid volume, the counting distance and the positioning variations are studied
      experimentally in a systematic way. A NaI and a germanium detector along with a
      realistic age-specific set of four thyroid phantoms were used to carry out this
      study. The thyroid phantom volumes correspond to the following ages: 5, 10, 15
      and adult. It was found that the counting efficiency varies linearly with the
      thyroid volumes for both detectors and whatever the phantom-detector distance is.
      The variation in counting distance strongly influences the measurement. Whatever
      the thyroid volume, a 30% difference in efficiency was found between the
      measurement at the contact and 1 cm for the NaI detector. A mathematical model
      giving the variation of the counting efficiency as a function of phantom-detector
      distance is provided. The study of positioning uncertainty has shown that the
      lateral/vertical displacements induce negligible efficiency variations and that
      it is relatively independent of the thyroid volume. The counting distance is a
      major parameter, which must be considered to assess the uncertainty of the
      subjects' measurements. The data reported here might serve to extract useful
      orders of magnitude when similar detectors are used. For other detectors, a
      similar trend might be expected and the information provided here could reduce
      the amount of experimental work needed to obtain it.

PMID- 29576556
TI  - Editor's Introduction to the Special Issue.

PMID- 29576557
TI  - Aging as Problem and as Mystery.
AB  - As human beings we live our lives simultaneously in two realms: the realm of
      problems, and the realm of mysteries. Each of these realms is associated with a
      different way of seeing, interpreting, and responding to the phenomena we
      encounter and experience in our lives, including the phenomenon of aging. This
      essay elaborates on the distinction between problems and mysteries as realms of
      thinking, feeling, and acting in the world, and applies this distinction to three
      aspects of the care of the elderly: delaying the aging process, dementia, and
      managing dying.

PMID- 29576558
TI  - Primary Prevention with a Capital <i>P</i>.
AB  - The survival of large segments of human populations to advanced ages is a
      crowning achievement of improvements in public health and medicine, but in the
      21st century, our continued desire to extend life brings forth a unique dilemma.
      The risk of death from chronic fatal diseases has declined, but even if it
      continues to do so in the future, the resulting longevity benefits are likely to
      diminish. It is even possible that unhealthy life expectancy could rise in the
      future as major fatal diseases wane. The reason for this is that the longer we
      live, the greater the influence of biological aging on the expression of fatal
      and disabling diseases. Research in gerontology has already demonstrated that
      aging is inherently modifiable, and that a therapeutic intervention that slows
      aging in people is a plausible target for science and public health. Given the
      speed with which population aging is progressing and chronic fatal and disabling
      conditions are challenging health-care costs across the globe, the case is now
      being made that delayed aging could be one of the most efficient and promising
      ways to combat disease, extend healthy life, compress morbidity, and reduce
      health-care costs.

PMID- 29576559
TI  - Where Has It Gone?: Writing, Loss, and Old Age.
AB  - Along with many others who have done research and writing on aging over the
      years, I was drawn to the topic by its social and economic importance. I could
      not help realizing in some vague way that I would one day become old myself. That
      thought tended to get brushed away, pushed under the rug along with other stray
      musings. All that began to change when I hit my 80s, intensifying even more as I
      went from 85 to 87. I was given an intensified introduction to doctors, disease,
      operations, and scans-and fear and anxiety. I also lost all interest in writing,
      my favorite activity. This is my story, which fortunately required writing.

PMID- 29576560
TI  - Serving the Very Sick, Very Frail, and Very Old: Geriatrics, Palliative Care, and
      Clinical Ethics.
AB  - How can we provide the best care for growing numbers of very frail, very sick, or
      very old people? The disciplines of geriatrics, palliative care, and clinical
      ethics each have a good deal to offer to improve care for elders, yet each field
      is saddled with heavy historical baggage. Using a case as a springboard, we
      address specific strengths and shortcomings of each field, and what these
      disciplines can learn from each other. Geriatrics is currently largely focused on
      prevention of disability, cognitive impairment, and death; it should reorganize
      around a palliative approach to providing care for elders living with multiple
      chronic conditions, disability, and dementia. Palliative care, while paying some
      attention to the spectrum of advanced illness, concentrates primarily on cancer;
      it should expand its central purpose to include providing supportive care to
      elders with serious illness and their caregivers. Ethics committee members and
      consultants principally stress individual autonomy; they need to expand their
      approach and develop longitudinal relationships with patients and family members,
      routinely incorporating them in deliberations and the crafting of
      recommendations. However, improving these three disciplines will only go so far
      toward improving the care of very frail, very sick, or very old people. What is
      most needed is longitudinal care provided by interdisciplinary primary care teams
      steeped in the core principles of all three disciplines.

PMID- 29576561
TI  - Organizing Eldercare for Geographic Communities.
AB  - The dramatically increasing prevalence of elderly persons disabled by conditions
      associated with aging could motivate reexamination of service delivery and
      financing for this population, seeking quality, reliability, and efficiency.
      Research and innovation have established many components of effective reforms,
      such as patient-directed care planning, encouragement of volunteer networks and
      family caregiving, mobilizing services to the home, adhering to patient goals and
      priorities, limiting poly-pharmacy, reducing the risk of falls, and providing
      adequate support services for people with disabilities. However, none have become
      widespread and rarely, if ever, are all of the evidence-based improvements
      available to a particular disabled elder. This essay argues that reform for
      disabled elders should be anchored in geographic communities, with a new
      organizational entity having responsibility for measuring performance and
      implementing improvements. This entity would use data and public input to set
      priorities, test improvement strategies, and take steps to assure adequate
      workforce and service supply. In this MediCaring Community, sustaining finances
      could come from local taxes or capturing the savings in Medicare that arise with
      optimal comprehensive services. Generating a new structure to monitor and manage
      eldercare services for a geographic community would be readily accomplished in
      some communities and would be worth testing.

PMID- 29576562
TI  - Merchants of Health: Shaping the Experience of Illness Among Older People.
AB  - Despite nearly universal health-care coverage for older Americans, the quality of
      care for the sickest and frailest remains sub-optimal. Understanding why requires
      analysis of the medical ecosystem. This paper considers the role of four of the
      principal actors in this system: physicians, hospitals, drug companies, and
      Medicare. Physicians spend more time in the office addressing diabetes and
      hypertension than they do evaluating falls and impaired cognition because of
      their training and their interests. Hospital administrators affect the hospital
      experience by investing in procedural specialties at the expense of low-tech,
      high-touch care. Pharmaceutical companies affect the medications older patients
      take by direct-to-consumer advertising and marketing to physicians. Medicare
      affects the patient's experience by prospective payment for hospitals, resulting
      in the burgeoning of post-acute care to accommodate early hospital discharges.
      Determining how to improve the quality of care for older people requires
      identifying a lever that affects the entire system. Medicare is uniquely
      positioned to serve this role. Reforming Medicare by introducing cost
      effectiveness criteria for reimbursement of expensive devices, by instituting
      requirements that medical resident training programs include exposure to
      multidisciplinary team care, and by introducing a new benefit package for the
      frail elderly could improve American geriatric care.

PMID- 29576563
TI  - "Losing My Self": A Poet's Ironies and a Daughter's Reflections on Dementia.
AB  - What can we learn about the experience of dementia and about ways of being human
      when a poet describes her forgetting? My mother, the poet Shirley Kaufman, died
      in 2016 at the age of 93. She had dementia for many years. By her mid-80s, many
      of her poems probed the experience of forgetting, including questions about the
      nature of self, memory, and thought, and the location of the past and the future.
      Her experience of forgetting revealed in her ninth and last collection, the
      widely acclaimed Ezekiel's Wheels (2009), serves as my entry point for an
      exploration of the self as it becomes dislocated in time yet remains attuned to
      and consciously aware of that dislocation. That dual quality of my mother's
      experience is the central, ironic tension explored in this essay. An intimate
      ethnography, this essay connects my mother's late-life poetry with my own
      experience, both as a daughter who watched her mother's state of mind unfold and
      as an anthropologist with extensive experience studying aging, late-life
      identity, illness, and the culture of medicine. Through the insights of my
      mother's poetic language I show how dementia can expose ironic features of
      selfhood, communication, and life itself that are worth our discernment. My hope
      is that my analysis may focus our gaze on the inherent tension in this form of
      life and teach us something new about identity, memory, and what is shared among
      us, those with and without the condition we call dementia.

PMID- 29576564
TI  - Cognitive Aging: What We Fear and What We Know.
AB  - Advances in the scientific understanding of the aging brain have led to the
      concept of cognitive aging. Physicians lag in their understanding of cognitive
      aging, and the public fear of mental deterioration is disproportionate to its
      true risk. Understanding cognitive aging requires recognition of its biological
      underpinnings and the functional changes which may result, as well as the
      variability across individuals through time and within individuals across
      different cognitive functions such as memory, knowledge, and reaction time. While
      there is no magic pill such as a vitamin that has been shown to improve our
      cognition in later life, several factors that are important well before the age
      of 65 impact subsequent cognitive aging, including education and a lifelong
      interest in cognitive stimulating activities. Sufficient evidence exists to
      recommend three interventions in later life: exercise, reducing cardiovascular
      risk factors, and careful attention to medications. Acceptance of the new
      paradigm of cognitive aging is essential to promote the quality of life of older
      people and will have repercussions throughout society.

PMID- 29576565
TI  - A Tale for Our Times: From the Bronx to Chicago in 76 Years.
AB  - This essay is a reflection on how personal history shapes who we are as we age
      and what matters to us, focusing on women. I begin by briefly recounting the
      formative aspects of my early years and midlife, and then show how these
      influence the choices I make in old age, as well as the concerns and anxieties I
      experience. I discuss lifestyle, family, and economic concerns, along with fear
      of dementia, and ageism. I conclude with a few comments about the kind of society
      that would facilitate decency and meaningful choice for the heterogeneous group
      who constitute America's aging.

PMID- 29576566
TI  - Social Determinants of Health at Older Ages: The Long Arm of Early and Middle
      Adulthood.
AB  - This article discusses the impacts of midlife social exposures on health in later
      life, especially for women. Of particular interest is the period of early
      adulthood. Social epidemiology and life course frameworks help reveal how
      workplace exposures, family dynamics, and public policies related to work and
      family shape opportunities in midlife that have long-run health consequences.
      This is especially important for American women, who have experienced health
      disadvantages over the last decades compared to women in similarly advanced
      industrialized countries. In most countries, single women are especially at high
      risk for poor health at older ages, and job strain can elevate future risks
      particularly for this subpopulation. Public policies such as maternity leave can
      reduce risks for poor mental health outcomes among working mothers 30 to 40 years
      after childbirth, suggesting that the period of early and middle adulthood may
      influence health trajectories well into old age.

PMID- 29576568
TI  - Modern Death Retold.
AB  - This review essay locates Haider Warraich's Modern Death: How Medicine Changed
      the End of Life (2017) in the lineage of books by physician writers who give us
      distinctive site lines into the veiled topic of human death and dying. A skilled
      storyteller, Warraich recombines established narratives on mortality and modern
      medicine and forges new emphases that underscore the socially mediated and
      negotiated dimensions of contemporary dying practices.

PMID- 29576567
TI  - No Country for Old Men: Four Challenges for Men Facing the Fourth Age.
AB  - This essay reads the protagonist of Cormac McCarthy's No Country for Old Men
      (2005), Sheriff Ed Tom Bell, as an exemplar of problems that contemporary aging
      men face when they look to ahead to the so-called Fourth Age. As the plot
      unfolds, Bell is an aging, increasingly ineffectual cowboy lawman who retires,
      renounces the violence that sustained his male dominance, and loses the moral
      certainty that ensured his identity. Like Bell, most old men struggle with four
      interrelated challenges as they move along the ever-lengthening journey of life:
      relevance, masculinity, love, and meaning.

PMID- 29576569
TI  - Use of digital impression systems with intraoral scanners for fabricating
      restorations and fixed dental prostheses.
AB  - Accurate impressions are essential in fabri-cating dental restorations and fixed
      dental prostheses. During the last decade, digital impression systems have
      improved substantially. This review discusses the accuracy of digital impression
      systems for fabrication of dental restorations and fixed dental prostheses. A
      literature search in PubMed was performed for the period from July 2010 through
      June 2017. The search keywords were Cerec, digital impression, direct
      digitalization, indirect digitalization, and intraoral scanner. Only relevant
      studies are summarized and discussed in this review. In general, the latest
      systems have considerably reduced the time required for impression making, and
      the accuracy and marginal fit of digital impression systems have recently
      improved. Restorations and fixed dental prostheses fabricated with currently
      available digital impression systems and intraoral scanners exhibit clinically
      acceptable ranges of marginal gap in both direct and indirect procedures.

PMID- 29576570
TI  - Gingival enlargement in children with sickle cell disease.
AB  - The purpose of the present study was to evaluate periodontal health status in
      children with sickle cell disease (SCD). Forty-nine children with SCD and 39
      systemically healthy sex- and age-matched children were enrolled in the study.
      Plaque index, gingival index, bleeding on probing, pocket depth, salivary volume,
      and hyperplastic index were recorded. In addition, the histopathological
      evaluation of gingiva was made in a child with SCD. There were significant
      differences between the groups with regard to hyperplastic index (P < 0.05),
      whereas there were no differences in other parameters. Gingival enlargement was
      detected in 27 children (55.1%) in the SCD group and 6 children (15.4%) in the
      control group (P < 0.001). However, there were no differences in periodontal
      health status of children in the SCD and control groups, the most important
      finding of this study that the gingival enlargement was more prevalent in
      children with SCD. Sickling and chronic inflammation seen in SCD may affect
      gingival tissues. Therefore, physicians and dentists must be aware of the effects
      of SCD on gingival tissues.

PMID- 29576571
TI  - Comparison of oral Candida carriage in waterpipe smokers, cigarette smokers, and
      non-smokers.
AB  - The aim of the present cohort study was to compare oral carriage of Candida in
      waterpipe smokers (WS), cigarette smokers (CS), and non-smokers (NS). A total of
      141 individuals (46 WS, 45 CS, and 50 NS) were included. A questionnaire was used
      to gather demographic information and data on the daily frequency and duration of
      smoking habits, the reasons for smoking, and daily oral hygiene maintenance
      habits. Oral Candida (C.) samples were cultured and yeast species were identified
      using polymerase chain reaction. Unstimulated whole salivary flow rate (UWSFR)
      was also recorded. The numbers of missing teeth (MT) were counted and tongue
      lesions were clinically identified. C. albicans was the most prevalent yeast
      species isolated from all groups. Oral C. albicans carriage was higher among WS
      (P < 0.05) and CS (P < 0.05) than among NS. Oral C. tropicalis carriage, age,
      UWSFR and the number of MT were comparable among the groups. Oral Candida
      carriage was significantly higher among WS and CS than among NS. Therefore it
      appears that WS and CS are at an increased risk of developing oral candida
      infections.

PMID- 29576572
TI  - Effect of demineralization time on the mineral composition and mechanical
      properties of remineralized dentin.
AB  - The aim of this study was to determine whether recovery of mineral levels
      restored the mechanical properties of dentin subjected to different durations of
      demineralization. Dentin at the floor of class 1 cavities (n = 12) was
      demineralized for 1, 2, and 3 weeks. Half the demineralized cavity floor was
      coated (control side), and a Fuji IX restoration was placed. The remaining half
      was therefore in contact with the Fuji IX restoration (test side). Simulated
      dentin tubular fluid was then supplied to each pulp chamber for 6 weeks. After
      remineralization, the teeth were detached from the system and sectioned.
      Concentrations of calcium, phosphorus, fluorine, and strontium and mechanical
      properties (hardness and Young's modulus) of the test and control sides were
      determined by electron probe microanalysis and nano-indentation, respectively.
      For remineralized dentin demineralized for 1 week, the substantial uptake of
      mineral elements restored hardness and Young's modulus at depths of 50 to 200 MUm
      from the lesion front. For longer periods of demineralization (2 and 3 weeks),
      structural damage to the demineralized dentin was severe and impeded recovery of
      mechanical properties, despite mineral uptake.

PMID- 29576573
TI  - Diagnostic reliability of 3.0-T MRI for detecting osseous abnormalities of the
      temporomandibular joint.
AB  - We compared the diagnostic reliability of 3.0-T magnetic resonance imaging (MRI)
      for detection of osseous abnormalities of the temporomandibular joint (TMJ) with
      that of the gold standard, cone-beam computed tomography (CBCT). Fifty-six TMJs
      were imaged with CBCT and MRI, and images of condyles and fossae were
      independently assessed for the presence of osseous abnormalities. The accuracy,
      sensitivity, and specificity of 3.0-T MRI were 0.88, 1.0, and 0.73, respectively,
      in condyle evaluation and 0.91, 0.75, and 0.95 in fossa evaluation. The McNemar
      test showed no significant difference (P > 0.05) between MRI and CBCT in the
      evaluation of osseous abnormalities in condyles and fossae. The present results
      indicate that 3.0-T MRI is equal to CBCT in the diagnostic evaluation of osseous
      abnormalities of the mandibular condyle.

PMID- 29576574
TI  - Efficiency of light curing units in a government dental school.
AB  - The light intensity of a light-curing unit is a crucial factor that affects the
      clinical longevity of resin composites. This study aimed to investigate the
      efficiency of light-curing units in use at a local governmental dental school for
      curing conventional and bulk-fill resin materials. A total of 166 light-curing
      units at three locations were examined, and the brand, type, clinic location,
      diameter of curing tip, tip cleanliness (using a visual score), and the output
      (in mW/cm2 using a digital radiometer) were recorded. Only 23.5% of the units
      examined had clean tips, with the graduate student clinical area containing the
      highest percentage of clean tips. Further, tips with poor cleanliness score
      values were associated with significantly lower output intensities. A small
      percentage (9.4%) of units was capable of producing intensities higher than 1,200
      mW/cm2 and lower than 600 mW/cm2 (7.6%). The majority of the low intensity units
      were located in the undergraduate student area, which also contained the highest
      number of units with intensities between 900 and 1,200 mW/cm2. The output of all
      the units in service was satisfactory for curing conventional resin composites,
      and most units were capable of curing bulk-fill resin materials.

PMID- 29576575
TI  - Cone-beam computed tomographic evaluation of changes in maxillary alveolar bone
      after orthodontic treatment.
AB  - This study examined the relationship of vertical and horizontal changes in the
      alveolar bone crest with upper incisor movement after orthodontic treatment.
      Tooth movement was measured on lateral cephalograms. Vertical and horizontal
      changes in the median alveolar crest and distance from the cementoenamel junction
      and anterior nasal spine to the alveolar crest were measured with cone-beam
      computed tomography. The incisal edge moved distally, and the cervical point
      intruded significantly and moved distally. The median alveolar crest decreased by
      3.80 +/- 2.05 mm. The distance from the labial cementoenamel increased
      significantly, by 0.35 +/- 0.38 mm. The vertical distance from the anterior nasal
      spine decreased significantly, and the alveolar crest moved distally. Vertical
      tooth movement was positively associated with change in the distance from the
      labial cementoenamel junction and inversely associated with vertical change in
      the distance from the anterior nasal spine on the labial and palatal sides.
      Lingual tooth movement was positively and negatively correlated with horizontal
      changes in the labial and palatal alveolar crest and vertical change in the
      palatal alveolar crest. The lingual movement of incisors was related to labial
      bone resorption. Greater lingual and extrusive movement of incisors led to a
      greater decrease in the alveolar bone crest.

PMID- 29576576
TI  - Successful conservative treatment of jaw osteonecrosis caused by denosumab in
      patients with multiple bone metastasis.
AB  - We report a case of osteonecrosis of the jaw (ONJ) associated with denosumab
      therapy in a 62-year-old female patient being treated for bone metastases from
      breast cancer. Upon initial presentation at the Department of Oral Medicine,
      Hokkaido University Hospital, the patient's mandibular molar teeth were extracted
      because of severe periodontal disease. Two months later, epithelialization of the
      sockets was observed and treatment with anti-resorptive drugs was started for
      bone metastases. One year after tooth extraction, bone exposure in the right
      lower first molar region was observed, and stage 2 medication-related ONJ (MRONJ)
      was diagnosed. Up to this time, the patient had received zoledronic acid twice
      and denosumab 22 times. Denosumab was discontinued by the oncologist, and oral
      antibiotics with rinsing of the exposed bone area were prescribed. By 36 weeks
      after discontinuation of denosumab, a sequestrum in the posterior part of the
      mandible was naturally shed, and the site was healed. Bisphosphonate is deposited
      in bones, whereas denosumab functions extracellularly and circulates in the
      blood. The effect of denosumab on bone remodeling is reversed shortly after the
      drug has been discontinued.

PMID- 29576577
TI  - Erratum to "Characterizations of oral microbiota in elderly nursing home
      residents with diabetes".
AB  - The publisher regrets that in the above-mentioned article, there was an error in
      the list of references. The reference numbers "29-32" should be "28-31".

PMID- 29576578
TI  - Release of antimicrobial compounds from a zinc oxide-chelate cement.
AB  - This study examined the release of cetylpyridinium chloride and benzalkonium
      chloride from fatty acid chelate temporary dental cement and their antimicrobial
      effects. The cement was Cavex Temporary, and either cetylpyridinium chloride or
      benzalkonium chloride was added (1% or 5% by mass), incorporating into the base
      paste. Release of the additives was determined by reverse-phase high-performance
      liquid chromatography. Possible chemical interactions between the cement
      components and additives were examined by Fourier transform infrared (FTIR)
      spectroscopy. Antimicrobial effects were assessed by measuring the zone of
      inhibition around sample discs after 24 h in a Streptococcus mutans culture. FTIR
      spectroscopy showed no interaction with cement components. For both additives,
      release was by diffusion for approximately the first 6 hours, with equilibration
      after about 2 weeks. Diffusion coefficients were 1.76 m2 s1/2 to 8.05 * 10-12 m2
      s1/2 and total release was 10.3 to 44.7% of additive loading. Zones of inhibition
      with additive were significantly larger than those for control discs. In
      conclusion, the antimicrobial properties of Cavex temporary cement are improved
      by the addition of the antimicrobial compounds cetylpyridium chloride and
      benzalkonium chloride, which are released by a diffusion process.

PMID- 29576579
TI  - Resonance frequency analysis of miniscrew implant stability.
AB  - This study used resonance frequency (RF) analysis to assess miniscrew implant
      (MSI) stability during wound healing in a sample of 68 patients (41 women, 27
      men; mean age, 27.7 years). The 104 MSIs included 66 placements in the buccal
      shelf (BS; 2.0 * 12 mm) and 38 placements in interradicular (IR; 1.5 * 8 mm)
      sites. Thirteen (12.5%) of the MSIs failed. A new RF detection device was used to
      measure RF at baseline (T0) and at 3 (T1), 6 (T2), 9 (T3), 12 (T4), and 15 (T5)
      weeks after placement. A linear mixed-effects model was fitted to change in RF
      values. As compared with the BS group, the IR group had significantly lower RF
      values on the right side from T0 through T4 and on the left side from T0 through
      T2. Insertion site and time of visit were significantly associated with RF value.
      The effects of time of visit significantly differed between the BS and IR sites.
      Starting from T0, the MSIs placed at both sites had significantly lower RF values
      at all intervals, except for T0-T1. Future studies should examine how the present
      clinical protocols can optimize timing of MSI loading to maximize the success
      rate.

PMID- 29576580
TI  - In vitro cytotoxic evaluation of novel fast-setting calcium silicate cement
      compositions and dental materials using colorimetric methyl-thiazolyl-tetrazolium
      assay.
AB  - A novel fast-setting calcium silicate cement with fluoride (CSC) has been
      developed for potential application in tooth crowns. This study compared the
      cytotoxicity of CSC compositions and a variety of dental materials. We tested CSC
      compositions (Protooth), MTA, Biodentine, Ketac Molar, Fuji II LC, Vitrebond,
      DeTrey Zinc, Dycal, and IRM, DMEM (negative control) and 1% NaOCl (positive
      control). After setting of cements for 24 h, specimens were immersed in DMEM for
      24 h to obtain material elutes. The elutes were serially diluted in serum-free
      DMEM to obtain three dilutions. L929 mouse fibroblast cells (1 * 104 cells per
      well) were treated for 24 h with elute dilutions (n = 3). Cytotoxicity was
      determined using methyl-thiazolyl-tetrazolium assay in triplicate. CSC
      compositions, MTA, and Biodentine showed no significant reduction in cell
      viability compared to DMEM. There was no significant difference in cell
      viability, at any of three dilutions, between CSC compositions and either MTA or
      Biodentine. Cytotoxicity was significantly lower for CSC compositions than for
      Vitrebond, DeTrey Zinc, Dycal, IRM, and 1% NaOCl, at all three dilutions, and
      undiluted Fuji II LC elute. In contrast to resin-modified glass ionomers, zinc
      phosphate cements, Dycal, and IRM, the CSC compositions showed no cytotoxic
      potential.

PMID- 29576581
TI  - Aggressive periodontitis presents a higher degree of bilateral symmetry in
      comparison with chronic periodontitis.
AB  - The purpose of this cross-sectional study was to evaluate the occurrence of
      bilateral symmetry in the distribution of clinical parameters in subjects with
      generalized aggressive periodontitis (GAP) and severe chronic periodontitis
      (SCP). The sample comprised 53 subjects with GAP and 33 with SCP. Probing depth
      (PD) and clinical attachment loss (CAL) were recorded from both buccal and
      lingual interproximal sites of incisors and molars. The symmetry of periodontal
      destruction was analyzed in terms of intraclass coefficient correlations (ICC)
      for pairs of contralateral sites at which PD and/or CAL was >=5 mm at one of the
      sites of the subjects in each group. GAP patients had a higher proportion of both
      PD and CAL >= 5 mm and also a higher mean proportion of subjects having PD and/or
      CAL >= 5 mm at one or both sites. The GAP group had 20 pairs of contralateral
      sites with PD (ICC = 0.22-0.63) and 26 pairs with CAL (ICC = 0.20-0.63), the
      correlation being statistically significant, while the SCP group had only 2 pairs
      (ICC = 0.36-0.48) with PD and 5 pairs with CAL (ICC = 0.33-0.58) showing a
      significant correlation. It can be concluded that GAP shows more symmetric
      periodontal destruction than SCP.

PMID- 29576582
TI  - The Reliability of Reduced Field-of-view DTI for Highly Accurate Quantitative
      Assessment of Cervical Spinal Cord Tracts.
AB  - PURPOSE: To compare the accuracy of fractional anisotropy (FA) and apparent
      diffusion coefficient (ADC) values between reduced FOV or so-called zonally
      oblique multislice (ZOOM) and conventional diffusion tensor imaging (DTI) in the
      cervical spinal cord. METHODS: Both ZOOM and conventional DTI were performed on
      10 healthy volunteers. Intraclass correlation coefficient (ICC) was used to
      evaluate the reliability of the measurements obtained. Four radiologists
      evaluated the FA and ADC values at each cervical cord level and classified the
      visibility by 4 ranks. The geometric distortion ratios of the long axis and short
      axis were compared between ZOOM and conventional DTI. The imaging parameters were
      as follows: b-value = 600 s/mm2; TR = 4500 ms; TE = 81 ms; FOV = 70 * 47 mm2 /
      200 * 200 mm2; matrix = 80 * 51 / 128 * 126 (ZOOM and conventional DTI,
      respectively). The region of interest was carefully drawn inside the spinal cord
      margin to exclude the spinal cord component, without excluding the white matter
      fiber tracts. RESULTS: The average FA value decreased in both ZOOM and
      conventional DTI in lower spinal cord levels; in contrast, the ADC value
      increased in lower spinal cord levels. Zonally oblique multislice DTI was
      superior to conventional DTI with regard to inter-rater and intra-rater
      reliability; further, visibility was better and the standard deviation was
      smaller in ZOOM DTI. On both the long and short axis, the geometric distortion
      ratio was lower in ZOOM DTI at all cervical spinal cord levels compared with the
      conventional DTI. There was a significant difference in the distortion ratios of
      the long and short axis between ZOOM and conventional DTI. CONCLUSION:
      Conventional DTI is unreliable owing to its susceptibility to the surrounding
      magnetic field. ZOOM DTI is reliable for performing highly accurate evaluations.

PMID- 29576583
TI  - Clinofibrate improved canine lipid metabolism in some but not all breeds.
AB  - The objectives of this study were to assess if Clinofibrate (CF) treatment
      improved lipid metabolism in dogs, and to clarify whether its efficacy is
      influenced by canine characteristics. We collected medical records of 306 dogs
      and performed epidemiological analyses. Lipid values of all lipoproteins were
      significantly decreased by CF medication, especially VLDL triglyceride (TG)
      concentration (mean reduction rate=54.82%). However, 17.65% of dogs showed drug
      refractoriness in relation to TG level, and Toy Poodles had a lower CF response
      than other breeds (OR=5.36, 95% CI=2.07-13.90). Therefore, our study suggests
      that genetic factors may have an effect on CF response, so genetic studies on
      lipid metabolism-related genes might be conducted to identify variations in CF
      efficacy.

PMID- 29576584
TI  - Oral Fat Sensitivity Is Associated with Social Support for Stress Coping in Young
      Adult Men.
AB  - Oral fat sensitivity (OFS), the ability to taste fat, is associated with eating
      habits in humans, including daily fatty food consumption; namely, proper OFS is
      important for health. In addition, lifestyle factors, such as stress and sleep,
      may affect fat intake. However, correlations between OFS, stress management, and
      sleep are largely unknown. Thus, we investigated the associations of OFS with
      lifestyle factors regarding stress management and daytime sleepiness in healthy
      young adult men. We measured OFS, sensitivities for three prototypical tastes
      (sweet, salty, and sour), and BMI in 22 subjects (27.2 +/- 6.0 years), who also
      completed a self-reported questionnaire on health, including lifestyle-related
      questions. The correlations of taste sensitivities with stress management and
      daytime sleepiness were analyzed. We thus found that the number of mentors for
      personal concerns (a question regarding stress management, social support) was
      positively associated with OFS (P = 0.041), but not the other taste
      sensitivities. In contrast, other lifestyle factors related to stress management
      (frequency of relaxation, frequency of eating when irritated or worried, and
      degree of satisfaction with one's sleep) and daytime sleepiness were not
      significantly associated with OFS, similar to that observed for other tested
      taste sensitivities. These results characterize the unique association of OFS
      with the degree of social support in healthy young men and provide novel insights
      into the nature of individual OFS differences. Thus, measuring the degree of
      social support may be helpful for the evaluation of OFS impairment, thereby
      contributing to the prevention of stress-induced overeating.

PMID- 29576585
TI  - Interleukin-35 as a New Biomarker of Renal Involvement in Lupus Nephritis
      Patients.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease
      with a wide range of clinical presentations. Lupus nephritis (LN) is the most
      serious manifestation of SLE. Interleukin-35 (IL-35), a member of the interleukin
      12 family, has been identified as a novel anti-inflammatory cytokine. In the past
      ten years, the role of IL-35 in inflammatory and autoimmune diseases has been
      studied extensively. Serum IL-35 levels, however, have not been studied in LN
      patients. The aim of the study was to determine serum IL-35 levels in SLE
      patients with and without nephritis, and their clinical values. The study was
      carried out on 120 SLE patients, which comprised 80 LN patients and 40 SLE
      patients without nephritis. SLE disease activity was measured according to
      Systemic Lupus Erythematosus Disease Activity Index-2 k (SLEDAI-2 k). Statistical
      evaluation was based on Mann-Whitney U-test, t-test, chi-square test, Spearman
      rank correlation test and Pearson's correlation test. The result showed that
      active SLE patients (n = 65) have lower serum IL-35 levels, compared to inactive
      SLE patients (n = 55, P < 0.001). Furthermore, serum IL-35 levels were
      significantly lower in LN patients (n = 80) than SLE patients without nephritis
      (n = 40, P = 0.013). Serum IL-35 levels had significant correlations with SLEDAI
      2k (r = -0.626, P < 0.001) in SLE patients and estimated glomerular filtration
      rate (eGFR) (r = 0.348, P = 0.002) in LN patients. These results indicate that IL
      35 is a potential biomarker of renal involvement in LN patients.

PMID- 29576586
TI  - Local Flow Patterns After Implantation of Bioresorbable Vascular Scaffold in
      Coronary Bifurcations - Novel Findings by Computational Fluid Dynamics.
AB  - BACKGROUND: Development of methods for accurate reconstruction of bioresorbable
      scaffolds (BRS) and assessing local hemodynamics is crucial for investigation of
      vascular healing after BRS implantation.Methods and Results:Patients with BRS
      that crossed over in a coronary bifurcation were included for analysis.
      Reconstructions of the coronary lumen and BRS were performed by fusion of optical
      coherence tomography and coronary angiography generating a tree model (TM) and a
      hybrid model with BRS (TM-BRS). A virtual BRS model with thinner struts was
      created and all 3 models were analyzed using computational fluid dynamics to
      derive: (1) time-average shear stress (TASS), (2) TASS gradient (TASSG), which
      represents SS heterogeneity, and (3) fractional flow reserve (FFR).
      Reconstruction of the BRS was successful in all 10 patients. TASS and TASSG were
      both higher by TM-BRS than by TM in main vessels (difference 0.27+/-4.30 Pa and
      10.18+/-27.28 Pa/mm, P<0.001), with a remarkable difference at side branch ostia
      (difference 13.51+/-17.40 Pa and 81.65+/-105.19 Pa/mm, P<0.001). With thinner
      struts, TASS was lower on the strut surface but higher at the inter-strut zones,
      whereas TASSG was lower in both regions (P<0.001 for all). Computational FFR was
      lower by TM-BRS than by TM for both main vessels and side branches (P<0.001).
      CONCLUSIONS: Neglecting BRS reconstruction leads to significantly lower SS and SS
      heterogeneity, which is most pronounced at side branch ostia. Thinner struts can
      marginally reduce SS heterogeneity.

PMID- 29576589
TI  - Contributions of UBE2C and UBE2S to meiotic progression of porcine oocytes.
AB  - Vertebrate oocytes arrested at the first meiotic prophase must proceed to the
      second meiotic metaphase (MII) before fertilization. This meiotic process
      requires the precise control of protein degradation. Part of the protein
      degradation in oocytes is controlled by members of the ubiquitin-conjugating
      enzyme family, UBE2C and UBE2S, which are known to participate in mono
      ubiquitination and poly-ubiquitination, respectively. Although UBE2 enzymes have
      been well studied in mitosis, their contribution to mammalian oocyte meiosis is
      relatively unknown and has been studied only in mice. Here, we investigated the
      contribution of UBE2C and UBE2S to porcine oocyte maturation using an RNA
      injection method. Overexpression of UBE2S prevented MII arrest of oocytes and led
      to the formation of a pronucleus (PN) at 48 h of culture. This effect was also
      observed for prolonged cultures of UBE2C-overexpressing oocytes, suggesting the
      effectiveness of poly-ubiquitination in the rapid escape from M-phase in porcine
      oocytes. Although the inhibition of either UBE2C or UBE2S by antisense RNA
      (asRNA) injection had no effect on oocyte maturation, asRNA-injected oocytes
      showed inhibited PN formation after parthenogenetic activation. These results
      indicated that ubiquitination of certain factors by UBE2S and UBE2C plays a role
      in the escape from MII arrest in porcine oocytes. Further investigations to
      identify the factors and how mono- and/or poly-ubiquitination contributes to
      protein degradation could provide a better understanding of UBE2 roles in oocyte
      maturation.

PMID- 29576590
TI  - Characterization of the Axillary Microbiota of Japanese Male Subjects with Spicy
      and Milky Odor Types by Pyrosequencing.
AB  - Malodorants in the human axilla are produced from human biogenic precursors by
      axillary bacterial enzymes. In the present study, we used pyrosequencing analysis
      to identify the axillary bacterial microbiota of 13 Japanese male subjects with
      cumin-like, spicy body odor (C type), and 9 with milky, skin-based body odor (M
      type). Anaerococcus, Corynebacterium, and Staphylococcus predominated in both C-
      and M-type subjects, followed by Moraxella and Peptoniphilus. These genera
      accounted for 96.2-99.9% of the total bacterial population, except in the
      microbiota of one C-type subject. However, the axillary bacteria in C-type
      subjects were more abundant than that in M-type subjects. These results suggest
      that the level of colonization by axillary bacteria is important for the
      production of malodorants.

PMID- 29576591
TI  - Role of Phage Shock Protein in Recovery of Heat-injured Salmonella.
AB  - Sublethally heat-injured cells of Salmonella in food can recover under favorable
      conditions, leading to foodborne illness. To elucidate the molecular mechanism of
      recovery from heat injury, the global changes in gene transcription of Salmonella
      Typhimurium were investigated in previous study. In this study, the functions of
      genes involved in phage shock response (viz., phage shock protein (psp) genes),
      the transcription levels of which were found in previous study to be increased
      during recovery from heat injury, were investigated in recovering cells. The
      increase in pspABCDEFG transcription levels during the recovery process was
      confirmed by qRT-PCR. To understand the role of psp genes in heat injury
      recovery, a pspA deletion mutant (DeltapspA) and a pspA-overexpressing strain (S.
      Typhimurium pBAD30/pspA (+) ) were constructed. DeltapspA showed slightly lower
      viable counts and membrane potential than those of the wild-type strain during
      recovery. On the other hand, there was no significant difference in the viable
      counts between S. Typhimurium pBAD30/pspA (+) and the control strains S.
      Typhimurium pBAD30/pspA (-) and S. Typhimurium pBAD30 (+) during recovery. It
      would seem that a lack of PspA protein alone somewhat affects the recovery of S.
      Typhimurium from heat injury, but overexpression of PspA alone is not sufficient
      to overcome this effect.

PMID- 29576592
TI  - Comparison of Chromogenic Selective Media for the Detection of Cronobacter spp.
      (Enterobacter sakazakii).
AB  - The four types of chromogenic selective media that are commercially available in
      Japan were compared for establishing a Japanese standard method for detecting
      Cronobacter spp. based on ISO/TS 22964:2006. When assessed using 9 standard
      Cronobacter spp. strains and 29 non-Cronobacter strains, Enterobacter sakazakii
      isolation agar, ChromocultTM Enterobacter sakazakii agar, CHROMagarTM E.
      sakazakii, and XM-sakazakii agar demonstrated excellent inclusivity and
      exclusivity. Using the ISO/TS 22964:2006 method, the recovered numbers of 38
      Cronobacter spp. strains, including 29 C. sakazakii isolates obtained from each
      medium, were equivalent, indicating that there was no significant difference (p >
      0.05) among the four types of chromogenic selective media. Thus, we demonstrated
      that these four chromogenic selective media are suitable alternatives when using
      the standard method for detecting Cronobacter spp. in Japan, based on the ISO/TS
      22964:2006.

PMID- 29576593
TI  - In vitro Inhibitory Effects of Two Bornean Medicinal Wild Gingers against
      Pathogenic Lagenidium thermophilum Infected Mud Crab Scylla tranquebarica.
AB  - The antifungal activity of two Bornean medicinal wild gingers Plagiostachys
      megacarpa and Zingiber phillippsiae were examined against Lagenidium
      thermophilum. The most active extract was P. megacarpa at concentration of 320
      ug/mL inhibiting both hyphal growth and zoospore production of L. thermophilum in
      24 h. Toxicity tests were conducted using mud crab (Scylla tranquebarica) larva.
      Bath treatment of P. megacarpa at concentrations of 320 and 640 ug/mL for 24 h
      were highly effective against hyphae and zoospores of the strain and it is non
      toxic to mud crab larva. Therefore, crude extracts P. megacarpa may be used as
      alternative treatment for marine Oomycete infection of mud crab.

PMID- 29576594
TI  - Advanced Analysis to Distinguish between Physical Decrease and Inactivation of
      Viable Phages in Aerosol by Quantitating Phage-Specific Particles.
AB  - Recent studies have investigated the efficacy of air-cleaning products against
      pathogens in the air. A standard method to evaluate the reduction in airborne
      viruses caused by an air cleaner has been established using a safe bacteriophage
      instead of pathogenic viruses; the reduction in airborne viruses is determined by
      counting the number of viable airborne phages by culture, after operating the air
      cleaner. The reduction in the number of viable airborne phages could be because
      of "physical decrease" or "inactivation". Therefore, to understand the mechanism
      of reduction correctly, an analysis is required to distinguish between physical
      decrease and inactivation. The purpose of this study was to design an analysis to
      distinguish between the physical decrease and inactivation of viable phi-X174
      phages in aerosols. We established a suitable polymerase chain reaction (PCR)
      system by selecting an appropriate primer-probe set for PCR and validating the
      sensitivity, linearity, and specificity of the primer-probe set to robustly
      quantify phi-X174-specific airborne particles. Using this quantitative PCR system
      and culture assay, we performed a behavior analysis of the phage aerosol in a
      small chamber (1 m3) at different levels of humidity, as humidity is known to
      affect the number of viable airborne phages. The results revealed that the
      reduction in the number of viable airborne phages was caused not only by physical
      decrease but also by inactivation under particular levels of humidity. Our study
      could provide an advanced analysis to differentiate between the physical decrease
      and inactivation of viable airborne phages.

PMID- 29576596
TI  - Effect of Side Branch Predilation in Coronary Bifurcation Stenting With the
      Provisional Approach - Results From the COBIS (Coronary Bifurcation Stenting) II
      Registry.
AB  - BACKGROUND: Whether side branch (SB) predilation before main vessel (MV) stenting
      is beneficial is uncertain, so we investigated the effects of SB predilation on
      procedural and long-term outcomes in coronary bifurcation lesions treated using
      the provisional approach.Methods and Results:A total of 1,083 patients with true
      bifurcation lesions undergoing percutaneous coronary intervention were evaluated.
      The primary outcome was a major adverse cardiovascular event (MACE): cardiac
      death, myocardial infarction, or target lesion revascularization. SB predilation
      was performed in 437 (40.4%) patients. Abrupt (10.5% vs. 11.3%; P=0.76) or final
      SB occlusion (2.7% vs. 3.9%; P=0.41) showed no differences between the
      predilation and non-predilation groups. The rates of angiographic success (69.1%
      vs. 52.9%, P<0.001) and SB stent implantation (69.1% vs. 52.9%, P<0.001) were
      significantly higher in the predilation group. During a median follow-up of 36
      months, we found no significant difference between the groups in the rate of MACE
      (9.4% vs. 11.5%; P=0.67) in a propensity score-matched population. In subgroup
      analysis, patients with minimal luminal diameter of the parent vessel <=1 mm
      benefited from SB predilation in terms of preventing abrupt SB occlusion (P for
      interaction=0.04). CONCLUSIONS: For the treatment of true bifurcation lesions, SB
      predilation improved acute angiographic and procedural outcomes, but could not
      improve long-term clinical outcomes. It may benefit patients with severe stenosis
      in the parent vessel.

PMID- 29576595
TI  - Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial
      Progenitors in Patients With Critical Limb Ischemia - The SCELTA Trial.
AB  - BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC)
      autotransplantation in critical limb ischemia (CLI) has been reported. Variable
      proportions of circulating monocytes express low levels of CD34
      (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs).
      The aim of the present randomized clinical trial was to compare the safety and
      therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC
      administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral
      blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected
      into the gastrocnemius of the affected limb in 23 and 17 patients, respectively.
      After a mean of 25.2+/-18.6-month follow-up, both groups showed significant and
      progressive improvement in muscle perfusion (primary endpoint), rest pain,
      consumption of analgesics, pain-free walking distance, wound healing, quality of
      life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC
      treated patients, there was a positive correlation between injected
      CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile
      was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the
      number of deaths and major amputations was lower compared with eligible untreated
      patients and historical reference patients. CONCLUSIONS: This study supports
      previous trials showing the efficacy of BM-MNC autotransplantation in CLI
      patients and demonstrates comparable therapeutic efficacy between BM-MNC and
      EPEPCs.

PMID- 29576597
TI  - Anticoagulation Therapy for Venous Thromboembolism in the Real World - From the
      COMMAND VTE Registry.
AB  - BACKGROUND: Venous thromboembolism (VTE) has a long-term risk of recurrence,
      which can be prevented by anticoagulation therapy.Methods and Results:The COMMAND
      VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with
      acute symptomatic VTE between January 2010 and August 2014. The entire cohort was
      divided into the transient risk (n=855, 28%), unprovoked (n=1,477, 49%), and
      cancer groups (n=695, 23%). The rate of anticoagulation discontinuation was
      highest in the cancer group (transient risk: 37.3% vs. unprovoked: 21.4% vs.
      cancer: 43.5% at 1 year, P<0.001). The cumulative 5-year incidences of recurrent
      VTE, major bleeding and all-cause death were highest in the cancer group
      (recurrent VTE: 7.9% vs. 9.3% vs. 17.7%, P<0.001; major bleeding: 9.0% vs. 9.4%
      vs. 26.6%, P<0.001; and all-cause death: 17.4% vs. 15.3% vs. 73.1%, P<0.001).
      After discontinuation of anticoagulation therapy, the cumulative 3-year incidence
      of recurrent VTE was lowest in the transient risk group (transient risk: 6.1% vs.
      unprovoked: 15.3% vs. cancer: 13.2%, P=0.001). The cumulative 3-year incidence of
      recurrent VTE beyond 1 year was lower in patients on anticoagulation than in
      patients off anticoagulation at 1 year in the unprovoked group (on: 3.7% vs. off:
      12.2%, P<0.001), but not in the transient risk and cancer groups (respectively,
      1.6% vs. 2.5%, P=0.30; 5.6% vs. 8.6%, P=0.44). CONCLUSIONS: The duration of
      anticoagulation therapy varied widely in discordance with current guideline
      recommendations. Optimal duration of anticoagulation therapy should be defined
      according to the risk of recurrent VTE and bleeding as well as death.

PMID- 29576598
TI  - Clinical Characteristics, Management, and Outcomes of Japanese Patients
      Hospitalized for Heart Failure With Preserved Ejection Fraction - A Report From
      the Japanese Heart Failure Syndrome With Preserved Ejection Fraction (JASPER)
      Registry.
AB  - BACKGROUND: Despite the specific characteristics of heart failure with preserved
      ejection fraction (HFpEF) having been demonstrated predominantly from registries
      in Western countries, important international differences exist in terms of
      patient characteristics, management and medical infrastructure between Western
      and Asian countries.Methods and Results:We performed nationwide registration of
      consecutive Japanese hospitalized HFpEF patients with left ventricular EF >=50%
      from 15 sites between November 2012 and March 2015. Follow-up data were obtained
      up to 2 years post-discharge. A total of 535 patients were registered. The median
      age was 80 years and 50% were female. The most common comorbid conditions were
      hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was
      relatively low. In-hospital mortality rate was 1.3% and the median length of
      hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all
      cause death or HF hospitalization. Approximately one-half of deaths had a cardiac
      cause. Lower serum albumin on admission was one of the strongest independent
      determinants of worse clinical outcome. CONCLUSIONS: Japanese HFpEF patients were
      less obese, but had a substantially higher prevalence of AF and lower incidence
      of subsequent events compared with previous reports. Our findings indicated that
      specific preventative and therapeutic strategies focusing on AF and nutritional
      status might need to be considered for Japanese hospitalized patients with HFpEF.

PMID- 29576599
TI  - New diagnostic criteria of adrenal subclinical Cushing's syndrome: opinion from
      the Japan Endocrine Society.
AB  - New diagnostic criteria and the treatment policy for adrenal subclinical
      Cushing's syndrome (SCS) are proposed on behalf of the Japan Endocrine Society.
      The Japanese version has been published, and the essential contents are presented
      in this English-language version. The current diagnostic criteria for SCS have
      elicited two main problems: (i) the relatively low reliability of a low range of
      serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone
      suppression test (DST); (ii) different cutoff values for serum cortisol after a 1
      mg DST compared with those of other countries. Thus, new criteria are needed. In
      the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8
      MUg/dL, after a 1-mg DST are presented. Serum cortisol >=5 MUg/dL after a 1-mg
      DST alone is considered sufficient to judge autonomous cortisol secretion for the
      diagnosis of SCS, and the current criterion based on serum cortisol >=3 MUg/dL
      after a 1-mg DST can continue to be used. Clinical evidence suggests that serum
      cortisol >=1.8-2.9 MUg/dL after a 1-mg DST is not always normal, so cases who
      meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level
      <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and
      nocturnal serum cortisol >=5 MUg/dL are proposed to have SCS. We suggest surgery
      if cases show serum cortisol >=5 MUg/dL after a 1-mg DST (or are disheartened by
      treatment-resistant problems) or suspicious cases of adrenal cancer according to
      tumor imaging.

PMID- 29576600
TI  - Tumor necrosis factor alpha improves glucose homeostasis in diabetic mice
      independent with tumor necrosis factor receptor 1 and tumor necrosis factor
      receptor 2.
AB  - Type 2 diabetes is a serious threat to human health all over the world. It is
      particularly important to look for the pathogenesis of type 2 diabetes.
      Researchers have found that obesity was associated with a broad chronic
      inflammatory response and type 2 diabetes. And tumor necrosis factor alpha (TNF
      alpha) is one of the most important cytokines related with obesity. To explore
      the functional role of TNF-alpha in the regulation of glucose homeostasis, TNF
      alpha receptor 1 and TNF-alpha receptor 2 double knockout (TNFR1/R2 DKO) mouse
      model were used in our study. After high fat diet (HFD) feeding, we detected that
      the insulin resistance was dramatically improved and circulated TNF-alpha was
      upregulated in TNFR1/R2 DKO mice. Surprisingly, glucose homeostasis was worsened,
      when we down regulate the levels of plasma TNF-alpha in TNFR1/R2 DKO mice by
      administering Adeno associated virus-shRNA-TNF-alpha (AAV-shTNF-alpha).
      Subsequently, in ob/ob mice, we confirmed that the glucose homeostasis could be
      improved when we up regulate the levels of plasma TNF-alpha by administering
      Adeno associated virus-TNF-alpha (AAV-TNF-alpha). Our findings suggested that
      TNFR1 and TNFR2 may not be the only receptors for TNF-alpha and TNF-alpha
      probably plays a positive role in reducing insulin resistance via a TNFRs
      independent way in diabetic mice.

PMID- 29576601
TI  - Genome Database of the Latvian Population (LGDB): Design, Goals, and Primary
      Results.
AB  - BACKGROUND: The Genome Database of the Latvian Population (LGDB) is a national
      biobank that collects, maintains, and processes health information, data, and
      biospecimens collected from representatives of the Latvian population. These
      specimens serve as a foundation for epidemiological research and prophylactic and
      therapeutic purposes. METHODS: Participant recruitment and biomaterial and data
      processing were performed according to specifically designed standard protocols,
      taking into consideration international quality requirements. Legal and ethical
      aspects, including broad informed consent and personal data protection, were
      applied according to legal norms of the Republic of Latvia. RESULTS: Since its
      start in 2006, the LGDB is comprised of biosamples and associated phenotypic and
      clinical information from over 31,504 participants, constituting approximately
      1.5% of the Latvian population. The LGDB represents a mixed-design biobank and
      includes participants from the general population as well as disease-based
      cohorts. The standard set of biosamples stored in the LGDB consists of DNA,
      plasma, serum, and white blood cells; in some cohorts, these samples are
      complemented by cancer biopsies and microbiome and urine samples. The LGDB acts
      as a core structure for the Latvian Biomedical Research and Study Centre (BMC),
      representing the national node of Latvia in Biobanking and BioMolecular resources
      Research Infrastructure - European Research Infrastructure Consortium (BBMRI
      ERIC). CONCLUSIONS: The development of the LGDB has enabled resources for
      biomedical research and promoted genetic testing in Latvia. Further challenges of
      the LGDB are the enrichment and harmonization of collected biosamples and data,
      the follow-up of selected participant groups, and continued networking and
      participation in collaboration projects.

PMID- 29576603
TI  - Socioeconomic Inequalities in Oral Health Among Unmarried and Married Women:
      Evidence From a Population-Based Study in Japan.
AB  - BACKGROUND: Socioeconomic inequalities in oral health have been reported in
      developed countries, but the influence of marital status has rarely been
      considered. Our aim was to examine marital status differentials in the
      association between socioeconomic status (SES) and oral health among community
      dwelling Japanese women. METHODS: From 2010 to 2011, a questionnaire survey was
      conducted among residents aged 25-50 years in Japanese metropolitan areas. Valid
      responses were received from 626 unmarried women and 1,620 married women. Women's
      own and husbands' educational attainment and equivalent income were used to
      assess SES. Self-rated "fair" or "poor" oral health was defined as poor oral
      health. Multiple logistic regression analysis was conducted to examine which SES
      indicators were associated with oral health. RESULTS: The prevalence of poor oral
      health was 21.1% among unmarried women and 23.8% among married women. Among
      unmarried women, equivalent income was not associated with oral health, but
      women's own education was significantly associated with oral health; the
      multivariate-adjusted odds ratio of poor oral health among those with high school
      education or lower compared to those with university education or higher was 2.14
      (95% confidence interval, 1.19-3.87). Among married women, neither women's own
      nor husbands' education was associated with oral health, but equivalent income
      was significantly associated with oral health, particularly among housewives; the
      multivariate-adjusted odds ratio of poor oral health among those in the lowest
      compared with highest income quartile was 1.57 (95% confidence interval, 1.08
      2.27). CONCLUSIONS: These findings indicate that marital status should be
      considered when examining associations between SES and oral health among Japanese
      women.

PMID- 29576604
TI  - Parental Internet Use and Lifestyle Factors as Correlates of Prolonged Screen
      Time of Children in Japan: Results From the Super Shokuiku School Project.
AB  - BACKGROUND: Prolonged screen time (ST), which includes TV viewing and gaming on
      smartphones and computers, is linked to poor health. Our aim was to explore the
      associations between school children with prolonged ST and parental internet use
      (IU) and lifestyles in Japan. METHODS: Children aged 6 to 13 years from the Super
      Shokuiku School Project, were surveyed using questionnaires in 2016. The survey
      assessed the grade, sex, and lifestyle of 1,659 children and parental internet
      use (IU) and lifestyle using Breslow's seven health behaviors. IU consisted of
      internet surfing and gaming on personal computers (PC), smartphones, or consoles.
      Three or more hours of ST was defined as prolonged ST, and its correlates were
      analyzed using logistic regression. RESULTS: Of all, 643 (38.8%) children spent
      >=2 hours/day of ST on a week day, whilst 153 (9.2%) children spent >=3
      hours/day. Prolonged ST was significantly associated with children in higher
      grade (odds ratio [OR] 1.74; 95% confidence interval [CI], 1.20-2.51), boys (OR
      2.16; 95% CI, 1.49-3.14), skipping breakfast (OR 1.88; 95% CI, 1.05-3.35), late
      bedtime (OR 1.80; 95% CI, 1.15-2.82), physical inactivity (OR 1.79; 95% CI, 1.12
      2.87), father's IU >=2 hours/day (OR 2.35; 95% CI, 1.52-3.63), mother's prolonged
      IU >=2 hours/day (OR 2.55; 95% CI, 1.43-4.52), mothers with unhealthy behaviors
      (OR 1.81; 95% CI, 1.05-3.13), no rule setting governing screen time (OR 2.41; 95%
      CI, 1.63-3.58), and mothers with full-time employment (OR 1.95; 95% CI, 1.06
      3.64). CONCLUSIONS: Prolonged ST among Japanese children was strongly associated
      with parental IU, no set rules for ST, and mother's unhealthy lifestyles. To
      reduce children's ST, parental engagement is warranted in the intervention
      strategy.

PMID- 29576602
TI  - Association of Adiponectin With Cancer and All-Cause Mortality in a Japanese
      Community-Dwelling Elderly Cohort: A Case-Cohort Study.
AB  - BACKGROUND: Most studies of plasma adiponectin (APN) and mortality among
      community-dwelling elderly focus on cardiovascular disease, but data on the
      relationship between plasma APN and cancer mortality is exiguous. We investigated
      whether APN is associated with cancer mortality in community-dwelling elderly
      people. METHODS: We conducted a case-cohort study within the New Integrated
      Suburban Seniority Investigation (NISSIN) Project using a randomly drawn sub
      cohort of 697 subjects (351 men and 346 women; mean age 64.5 [standard deviation,
      0.5] years) among whom we compared cases of all-cause death (n = 269) and cancer
      death (n = 149) during a mean follow-up duration of 10.8 (standard deviation,
      3.7) years. Associations between APN and mortality were assessed using weighted
      Cox regression analyses. RESULTS: We observed significant positive associations
      between the APN concentration and cancer death in the first and third APN
      tertiles compared with the second APN tertile (hazard ratio [HR]T1 vs T2, 1.67;
      95% confidence interval [CI], 1.00-2.79 and HRT3 vs T2, 2.10; 95% CI, 1.30-3.40).
      Further adjustment for possible confounders attenuated the association (HRT1 vs
      T2, 1.63; 95% CI, 0.93-2.84 and HRT3 vs T2, 2.10; 95% CI, 1.26-3.50). A similar
      but weaker association was seen for all-cause mortality (multivariate HRT1 vs T2,
      1.45; 95% CI, 0.95-2.21 and HRT3 vs T2, 1.51; 95% CI, 1.01-2.25). CONCLUSION:
      Plasma APN and cancer mortality have a significant relationship among community
      dwelling elderly people, which warrants further study.

PMID- 29576605
TI  - MAP Kinase-Interacting Kinase 1 Promotes Proliferation and Invasion of
      Hepatocellular Carcinoma and Is an Unfavorable Prognostic Biomarker.
AB  - BACKGROUND Hepatocellular carcinoma (HCC) accounts for one of the most prevalent
      tumor types in the world. The MAP kinase-interacting kinase 1 (MNK1) functions
      downstream of MAP kinases such as p38 and ERK, and its potential role in cancer
      development is being uncovered. The aim of this study was to investigate the
      expression and function of MNK1 in HCC. MATERIAL AND METHODS Immunohistochemical
      staining and quantitative PCR were performed to explore the expression of MNK1 in
      both HCC tissues and adjacent normal liver tissues. Chi-square test, univariate
      analysis, and multivariate analysis were conducted to statistically evaluate
      clinical significance of MNK1 in HCC. Proliferation, migration, and invasion
      capacities of HCC cells were assessed after overexpressing or silencing MNK1.
      RESULTS Both the RNA and protein levels of MNK1 were upregulated in HCC tissues
      compared to normal liver tissues. High expression of MNK1 was correlated with
      advanced tumor stage and poor overall survival. Moreover, MNK1 was identified as
      a novel independent prognostic factor for HCC patients. Cellular studies showed
      that MNK1 can enhance the proliferation, migration, and invasion capacities of
      HCC cells, thereby promoting tumor progression. CONCLUSIONS High expression of
      MNK1 is frequent in HCC tissues, which promotes tumor proliferation and invasion,
      and is correlated with a poor overall survival. Targeting MNK1 may be a novel
      direction for the drug development of HCC therapy.

PMID- 29576606
TI  - Gastric Metastasis as the First Presentation One Year Before Diagnosis of Primary
      Breast Cancer.
AB  - BACKGROUND Metastasis to the stomach can be found as the first presentation of
      breast cancer, although it is very rare. The authors report an unusual case of
      metastasis to the stomach as the first presentation of breast cancer, which had a
      good prognosis. CASE REPORT A 51-year-old female underwent radical subtotal
      gastrectomy and chemotherapy because of gastric cancer with distant metastasis.
      At the time of diagnosis of gastric cancer, she had a negative result from
      routine mammography. One year later, a newly detected lesion on routine
      mammography was confirmed as breast cancer. Initial diagnosis of gastric cancer
      was changed to metastatic carcinoma from breast cancer through
      immunohistochemistry after bilateral mastectomy. After the completion of
      chemotherapy, she is currently receiving treatment with letrozole, without
      recurrence for 66 months. CONCLUSIONS Considering metastasis from breast cancer
      might be needed when unusual presentation of gastric cancer is observed even
      though gastric cancer is still one of the most common malignancies in Korea.
      Immunohistochemical analysis is helpful for diagnosis. Surgery for metastatic
      carcinoma of the stomach could be another option for treatment.

PMID- 29576607
TI  - The career intentions, work-life balance and retirement plans of UK dental
      undergraduates.

PMID- 29576608
TI  - Evaluating major curriculum change: the effect on student confidence.

PMID- 29576609
TI  - Initiating research in a private dental practice.
AB  - Research is an intrinsic part of both academia and clinical best practice. Within
      an academic environment, this can include access to advice and guidance from
      trained professionals. Similarly, while sometimes overly risk-averse, within the
      NHS there is a structured and systematic approach to healthcare research.
      However, in the UK, a large number of specialist dental procedures take place
      within the private healthcare system, which does not have access to such support
      and guidance. How, then, can we generate our own dental research from private
      dental primary care settings? With a number of phrases becoming part of everyday
      vocabulary in dental primary care, such as practice-based research, patient
      centred outcomes, evidence-based dentistry, it is time to consider this. From
      research ethics to writing papers, via GCP, IRAS, HEIs and MOOCs, this article
      summarises the experiences of one non-affiliated (non-academic, non-NHS) private
      dental practice attempting to enter the world of research. The authors discuss
      their experiences, share the multiple sources of support encountered along the
      way, and demonstrate the benefits to everyday practice gained by initiating
      research studies.

PMID- 29576610
TI  - The referral and management process of patients sustaining peri-anaesthetic dento
      alveolar trauma: an audit.

PMID- 29576611
TI  - Oral health knowledge, perceptions and practices among parents, guardians and
      teachers in South Wales, UK: A qualitative study.

PMID- 29576612
TI  - Protein kinase A-mediated phosphorylation regulates STAT3 activation and
      oncogenic EZH2 activity.
AB  - Polycomb repressive complex 2 (PRC2) member enhancer of zeste homolog 2 (EZH2)
      trimethylates histone H3 lysine 27 (H3K27me3), alters chromatin structure and
      contributes to epigenetic regulation of gene expression in normal and disease
      processes. Phosphorylation of EZH2 augmented EZH2 oncogenic activity in cancer
      but observations have been limited to threonine 350 (T350) and serine 21 (S21)
      residues by cyclin-dependent kinase 1 and protein kinase B, respectively. In
      addition, phosphorylation of the evolutionarily conserved T372 motif of EZH2 by
      p38 resulted in EZH2 interaction with Ying Yang 1 and promoted muscle stem cell
      differentiation. In the present study, we used epithelial ovarian cancer (OC)
      cells as a model to demonstrate that phosphorylation of EZH2 at T372 by protein
      kinase A (PKA) induced a dominant-negative EZH2 phenotype, inhibited OC cell
      proliferation and migration in vitro and decreased ovarian xenograft tumor growth
      in vivo. Phosphorylation of T372 by PKA enhanced the interaction between EZH2 and
      signal transducer and activator of transcription 3 (STAT3), and STAT3 binding to
      pT372-EZH2 reduced cellular levels of pSTAT3 and downregulated interleukin 6
      receptor expression in OC. Furthermore, PKA-mediated pT372-EZH2 decreased ATP
      levels and altered mitochondrial gene expression, resulting in mitochondrial
      dysfunction and reduced OC cell growth. These findings demonstrate that PKA
      mediated T372 phosphorylation reduces oncogenic EZH2 activity and reveal a novel
      role for pT372 in regulating EZH2 in OC and possibly other cancers.

PMID- 29576613
TI  - HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like
      phenotype.
AB  - HOXB7 is a homeodomain (HOX) transcription factor involved in regional body
      patterning of invertebrates and vertebrates. We previously identified HOXB7
      within a ten-gene prognostic signature for lung adenocarcinoma, where increased
      expression of HOXB7 was associated with poor prognosis. This raises the question
      of how HOXB7 overexpression can influence the metastatic behavior of lung
      adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung
      cancer expression datasets and found that HOXB7-overexpressing tumors are
      enriched in gene signatures characterizing adult and embryonic stem cells (SC),
      and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7
      upregulates several canonical SC/iPSC markers and sustains the expansion of a
      subpopulation of cells with SC characteristics, through modulation of LIN28B, an
      emerging cancer gene and pluripotency factor, which we discovered to be a direct
      target of HOXB7. We validated this new circuit by showing that HOXB7 enhances
      reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC,
      which is a canonical reprogramming factor.

PMID- 29576614
TI  - Human genetics: Population-scale family trees from publicly available data.

PMID- 29576616
TI  - The ethics of patenting autism genes.

PMID- 29576615
TI  - Enhancing the accuracy of next-generation sequencing for detecting rare and
      subclonal mutations.
AB  - Mutations, the fuel of evolution, are first manifested as rare DNA changes within
      a population of cells. Although next-generation sequencing (NGS) technologies
      have revolutionized the study of genomic variation between species and individual
      organisms, most have limited ability to accurately detect and quantify rare
      variants among the different genome copies in heterogeneous mixtures of cells or
      molecules. We describe the technical challenges in characterizing subclonal
      variants using conventional NGS protocols and the recent development of error
      correction strategies, both computational and experimental, including consensus
      sequencing of single DNA molecules. We also highlight major applications for low
      frequency mutation detection in science and medicine, describe emerging
      methodologies and provide our vision for the future of DNA sequencing.

PMID- 29576617
TI  - What do we know about the macular pigment in AMD: the past, the present, and the
      future.
AB  - Carotenoids are lipophilic isoprenoid pigments with a common C40H56 core chemical
      structure that are naturally synthesized by many plants, algae, bacteria, and
      fungi. Humans and animals cannot synthesize carotenoids de novo and must obtain
      them solely through dietary sources. Among the more than 750 carotenoids in
      nature, only lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites
      selectively accumulate in the foveal region of the retina where they are
      collectively referred to as the macular pigment (MP) of the macula lutea. MP
      serves an ocular protective role through its ability to filter phototoxic blue
      light radiation and also via its antioxidant activity. These properties have led
      to the hypothesis that carotenoids may protect against the development of age
      related macular degeneration (AMD), the most common cause of blindness in the
      aged population >60 years old. Epidemiological studies have supported this by
      showing that patients with lower concentrations of serum carotenoids and macular
      pigment optical density (MPOD) measurements are at a higher risk of developing
      AMD. Conversely, nutritional supplementation and diets rich in lutein and
      zeaxanthin readily impact MP concentrations and reduce the risk of progression to
      advanced AMD, and the AREDS2 supplement formulation containing 10 mg of lutein
      and 2 mg of zeaxanthin is the standard-of-care recommendation for individuals at
      risk for visual loss from advanced AMD. This article reviews the rich history of
      research on the MP dating back to the 1700s and outlines their potential for
      further therapeutic improvements for AMD in the future.

PMID- 29576619
TI  - Breaking the code of antibiotic resistance.

PMID- 29576618
TI  - Effects of collagen cross-linking on the keratoconus metabolic network.
AB  - PURPOSE: Keratoconus (KC) is a multifactorial, ectatic corneal disease. Metabolic
      changes in the corneal stroma with alterations in collagen fibril stability,
      oxidative stress, and urea cycle, have previously been reported as key players in
      KC pathobiology. Recently, corneal collagen cross-linking (CXL) has been
      introduced as a treatment that can address the progressive nature of KC. While
      the treatment has been successful in the early days, it is not without clinical
      ramifications. In this study, we investigated the alterations in KC metabolic
      profiles due to CXL. METHODS: Primary human corneal fibroblasts (HCFs) from
      healthy donors and human KC fibroblasts (HKCs) from KC donor patients were plated
      on transwell polycarbonate membranes and stimulated by a stable vitamin C. At 4
      weeks, riboflavin was added to the cultures followed by UVA irradiation (365 nm).
      Using mass spectrometry, we measured the major differences in metabolites in HKCs
      compared to HCFs pre- and post CXL. RESULT: The analysis of 276 metabolites in
      HCFs and HKCs revealed that the most affected metabolites due to CXL were
      glutathione disulfide, ascorbic acid, proline, and lysine. A significant decrease
      in the pro-inflammatory biomarkers (myo-inositol and histidine) was also
      observed. Furthermore, a significant downregulation of many amino acids, lactate
      levels, and other water-soluble metabolites was noted in HKCs following CXL.
      CONCLUSION: CXL is a KC treatment available to patients within certain criteria.
      Surprisingly, the cellular and molecular mechanisms are considerably understudied
      limiting our ability for more precise and targeted CXL treatments. In this study,
      for the first time, we report the effects of CXL on KC metabolism.

PMID- 29576620
TI  - Marine microbiology: Carbon export into the deep ocean.

PMID- 29576621
TI  - The mechanism study of lentiviral vector carrying methioninase enhances the
      sensitivity of drug-resistant gastric cancer cells to Cisplatin.
AB  - BACKGROUND: To investigate the mechanism of lentiviral vector carrying
      methioninase enhances the sensitivity of drug-resistant gastric cancer cells to
      Cisplatin. METHODS: Death receptors, anti-apoptotic protein, NF-kappaB, and TRAIL
      pathway-related factors were detected. The influence of LV-METase transfection on
      cell viability and pathway-related proteins were assessed by MTT method and
      western blot, respectively. Different treatments (NF-kappaB or caspase-3
      inhibitor induction, TRAIL supplement, etc.) were performed in gastric cancer
      cells and the above parameters were analysed. Moreover, the connection between
      miR-21 and NF-kappaB or caspase-8 was determined by Chip and luciferase assay,
      respectively. LV-METase transfection drug-resistant gastric cancer cells were
      injected subcutaneously into mice. RESULTS: The expression of free MET, miR-21
      5p, MDR1, P-gp, and DR5 was significantly increased in drug-resistant gastric
      cancer cell lines. When cells were transfected with LV-METase, intracellular
      TRAIL signalling was activated while NF-kappaB pathway was inhibited. Besides,
      enhanced TRAIL signalling or repressed NF-kappaB pathway can promote the
      sensitivity of drug-resistant strains to Cisplatin, and the combination shows
      more sensitive to sensitisation. LV-METase promoted TRAIL expression by reducing
      NF-kappaB, thereby contributing to the downregulation of P-gp and enhancing the
      susceptibility of drug-resistant gastric cancer cells to Cisplatin. Furthermore,
      miR-21 regulated by NF-kappaB mediated the expression of P-gp protein via
      inhibiting caspase-8, thus regulating Cisplatin-induced cell death. CONCLUSIONS:
      Our results suggest that LV-METase has potential as a therapeutic agent for
      gastric cancer treatment.

PMID- 29576622
TI  - Predicting cumulative incidence of adverse events in older patients with cancer
      undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG)
      multicentre prospective study.
AB  - BACKGROUND: Older patients have increased risk of toxicity from chemotherapy.
      Current prediction tools do not provide information on cumulative risk. METHODS:
      Patients aged >= 70 years with solid cancer were prospectively enrolled. A
      prediction model was developed for adverse events (AEs) >= Grade 3 (G3), based on
      geriatric assessment (GA), laboratory, and clinical variables. RESULTS: 301
      patients were enrolled (median age, 75 years). Median number of chemotherapy
      cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs
      >= G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological
      stress or acute disease in the past 3 months, water consumption < 3 cups/day,
      unable to obey a simple command, and self-perception of poor health were
      significantly related with AEs >= G3. A predicting model with these six variables
      ranging 0-8 points was selected with the highest discriminatory ability (c
      statistic= 0.646), which could classify patients into four risk groups. Predicted
      cumulative incidence of AEs >= G3 was discriminated according to risk groups.
      CONCLUSIONS: This prediction tool could identify the risk of AEs >= G3 after
      chemotherapy and provide information on the cumulative incidence of AEs in each
      cycle. CLINICAL TRIAL ID: WHO ICTRP number, KCT0001071.

PMID- 29576623
TI  - Optoacoustics delineates murine breast cancer models displaying angiogenesis and
      vascular mimicry.
AB  - BACKGROUND: Optoacoustic tomography (OT) of breast tumour oxygenation is a
      promising new technique, currently in clinical trials, which may help to
      determine disease stage and therapeutic response. However, the ability of OT to
      distinguish breast tumours displaying different vascular characteristics has yet
      to be established. The aim of the study is to prove OT as a sensitive technique
      for differentiating breast tumour models with manifestly different vasculatures.
      METHODS: Multispectral OT (MSOT) was performed in oestrogen-dependent (MCF-7) and
      oestrogen-independent (MDA-MB-231) orthotopic breast cancer xenografts. Total
      haemoglobin (THb) and oxygen saturation (SO2MSOT) were calculated. Pathological
      and biochemical evaluation of the tumour vascular phenotype was performed for
      validation. RESULTS: MCF-7 tumours show SO2MSOT similar to healthy tissue in both
      rim and core, despite significantly lower THb in the core. MDA-MB-231 tumours
      show markedly lower SO2MSOT with a significant rim-core disparity. Ex vivo
      analysis revealed that MCF-7 tumours contain fewer blood vessels (CD31+) that are
      more mature (CD31+/aSMA+) than MDA-MB-231. MCF-7 presented higher levels of
      stromal VEGF and iNOS, with increased NO serum levels. The vasculogenic process
      observed in MCF-7 was consistent with angiogenesis, while MDA-MB-231 appeared to
      rely more on vascular mimicry. CONCLUSIONS: OT is sensitive to differences in the
      vascular phenotypes of our breast cancer models.

PMID- 29576624
TI  - Long-term follow-up of overall survival for cabozantinib versus everolimus in
      advanced renal cell carcinoma.
AB  - BACKGROUND: In the phase 3 METEOR trial (NCT01865747), cabozantinib significantly
      improved progression-free survival, overall survival, and objective response rate
      compared with everolimus in patients with advanced renal cell carcinoma (RCC)
      after prior antiangiogenic therapy. A statistically significant improvement in
      overall survival was observed at a second interim analysis with 320 recorded
      deaths. METHODS: 658 patients with advanced RCC who had received at least one
      prior VEGFR tyrosine kinase inhibitor were randomised 1:1 to cabozantinib (60 mg
      daily) or everolimus (10 mg daily). Survival follow-up continued to reach the 408
      deaths that were pre-specified for the final analysis. RESULTS: With 430 deaths
      (198 for cabozantinib and 232 for everolimus), median overall survival was 21.4
      months with cabozantinib and 17.1 months with everolimus (HR 0.70, 95% CI 0.58
      0.85; P = 0.0002). Safety profiles of cabozantinib and everolimus were consistent
      with those reported previously. CONCLUSIONS: Cabozantinib significantly improved
      overall survival compared with everolimus in previously treated patients with
      advanced RCC with consistent results after long-term follow-up.

PMID- 29576626
TI  - A message for 2018.

PMID- 29576625
TI  - Targeting glutaminolysis in chondrosarcoma in context of the IDH1/2 mutation.
AB  - INTRODUCTION: Chondrosarcoma is a malignant cartilage-forming bone tumour in
      which mutations in IDH1 and IDH2 frequently occur. Previous studies suggest an
      increased dependency on glutaminolysis in IDH1/2 mutant cells, which resulted in
      clinical trials with the drugs CB-839, metformin and chloroquine. In this study,
      the preclinical rationale for using these drugs as a treatment for chondrosarcoma
      was evaluated. METHODS: Expression of glutaminase was determined in 120 cartilage
      tumours by immunohistochemistry. Ten chondrosarcoma cell lines were treated with
      the metabolic compounds CB-849, metformin, phenformin (lipophilic analogue of
      metformin) and chloroquine. RESULTS: A difference in glutaminase expression
      levels between the different tumour grades (p = 0.001, one-way ANOVA) was
      identified, with the highest expression observed in high-grade chondrosarcomas.
      Treatment with CB-839, metformin, phenformin or chloroquine revealed that
      chondrosarcoma cell lines are sensitive to glutaminolysis inhibition. Metformin
      and phenformin decreased mTOR activity in chondrosarcoma cells, and metformin
      decreased LC3B-II levels, which is counteracted by chloroquine. CONCLUSION:
      Targeting glutaminolysis with CB-839, metformin, phenformin or chloroquine is a
      potential therapeutic strategy for a subset of high-grade chondrosarcomas,
      irrespective of the presence or absence of an IDH1/2 mutation.

PMID- 29576627
TI  - Correction: Broadening the phenotypic spectrum of pathogenic LARP7 variants: two
      cases with intellectual disability, variable growth retardation and distinct
      facial features.
AB  - Correction to: Journal of Human Genetics (2016) 61, 229-33
      https://doi.org/10.1038/jhg.2015.134 ; published online 26 November 2015.

PMID- 29576628
TI  - Photoacoustic technique to measure temperature effects on microbubble
      viscoelastic properties.
AB  - Phospholipid-coated microbubbles are being developed for several biomedical
      applications, but little is known about the effect of temperature on the
      viscoelastic properties of the shell. Here, we report on the use of a
      photoacoustic technique to study the shell properties of individual microbubbles
      as a function of temperature. The microbubbles were driven into small-amplitude
      oscillations by ultrasound waves generated from the absorption of an intensity
      modulated infrared laser, and these oscillations were detected by forward-light
      scattering of a second blue laser. The drive laser modulation frequency was swept
      to determine the resonant response of 2-4 MUm radius microbubbles. Lipid shell
      elasticity and viscosity were determined by modeling the microbubble response as
      a linear harmonic oscillator. The results from slow heating showed a linear
      decrease in elasticity and viscosity between 21 and 53  degrees C and a
      corresponding increase in the maximum oscillation amplitude. Rapid heating to 38 
      degrees C, on the other hand, showed a transient response in the viscoelastic
      properties, suggesting shell rupture and reformation during microbubble growth
      and subsequent dissolution. These effects are important for biomedical
      applications, which require warming of the microbubbles to body temperature.

PMID- 29576629
TI  - Update Breast Cancer 2018 (Part 1) - Primary Breast Cancer and Biomarkers.
AB  - This summary provides an overview of how new therapies or new aspects of
      established therapies relate to the latest findings. Neoadjuvant therapy, local
      therapy, new aspects of systemic therapy, and prognostic and predictive factors
      are presented. In the neoadjuvant setting, the association between pathological
      complete response (pCR) and prognosis is still of interest as is the
      identification of new molecular predictors for new therapies such as CDK4/6
      inhibitors. As regards surgical treatment, the target is still to reduce the
      aggressiveness of surgery. To achieve this, a better understanding particularly
      of ductal carcinoma in situ is required. With regard to systemic therapy, more
      data on the best combinations and therapy sequences for existing therapies is
      available. Finally, the use of prognostic and predictive factors may help to
      avoid overtreatment and ensure that patients only receive therapies which have
      been shown to be effective for their specific condition and have fewer side
      effects.

PMID- 29576630
TI  - Update Breast Cancer 2018 (Part 2) - Advanced Breast Cancer, Quality of Life and
      Prevention.
AB  - The treatment of metastatic breast cancer has become more complicated due to
      increasing numbers of new therapies which need to be tested. Therapies are now
      being developed to treat special clinical or molecular subgroups. Even though
      intrinsic molecular subtypes play a major role, more and more new therapies for
      subgroups and histological subtypes are being developed, such as the use of PARP
      inhibitors to treat patients with BRCA mutations (breast and ovarian cancer).
      Supportive therapies are also evolving, allowing problems such as alopecia or
      nausea and vomiting to be treated more effectively. Treatment-related side
      effects have a direct impact on the prognosis of patients with metastatic breast
      cancer, and supportive therapy can improve compliance. Digital tools could be
      useful to establish better patient management systems. This overview provides an
      insight into recent trials and how the findings could affect routine treatment.
      Current aspects of breast cancer prevention are also presented.

PMID- 29576631
TI  - Active Immunisation with Partner Lymphocytes in Female Patients Who Want to
      Become Pregnant - Current Status.
AB  - Around 1 - 3% of all couples who try to have a child are affected by recurrent
      miscarriage. According to the WHO, recurrent miscarriage is defined as the
      occurrence of three or more consecutive miscarriages up to the 20th week of
      pregnancy. There are various causes of recurrent miscarriage; in many cases, the
      causes remain unclear, with the result that immunological factors are one of the
      possible causes discussed. For the mother's immune system, the embryo represents
      a semi-allogeneic transplant, as half of the embryo's genes are of paternal
      origin. In place of a conventional immune response, the embryo induces a
      secondary protection mechanism, which contributes to the successful implantation.
      When performing immunisation with partner lymphocytes, the patient receives an
      intradermal injection of her partner's prepared lymphocytes into the volar side
      of the forearm in order to induce immunomodulation with a consequently increased
      rate of pregnancy and live birth. A prerequisite for this procedure is that all
      other possible causes of sterility have been ruled out in advance. Due to the
      highly heterogeneous nature of the data, a significant benefit as a result of the
      immunisation cannot yet be clearly proven. However, there are signs that the
      therapy may be effective when using lymphocytes that have been extracted as short
      a time beforehand as possible. Overall, the treatment represents a safe, low-risk
      procedure. Following a detailed informative discussion with the couple regarding
      the chances of success and following a detailed review of the indication and
      contraindications, immunisation with partner lymphocytes can be discussed with
      the couple on a case-by-case basis - provided that all other possible causes of
      sterility have been ruled out in advance.

PMID- 29576633
TI  - mTor Inhibitors for the Treatment of Endometriosis.

PMID- 29576632
TI  - Maternal Thrombophilia and Recurrent Miscarriage - Is There Evidence That Heparin
      is Indicated as Prophylaxis against Recurrence?
AB  - Background: Recurrent miscarriage, also referred to as recurrent spontaneous
      abortion (RSA), affects 1 - 5% of couples and has a multifactorial genesis.
      Acquired and congenital thrombophilia have been discussed as hemostatic risk
      factors in the pathogenesis of RSA. Method: This review article was based on a
      selective search of the literature in PubMed. There was a special focus on the
      current body of evidence studying the association between RSA and
      antiphospholipid syndrome and hereditary thrombophilia disorders. Results:
      Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia and
      recurrent miscarriage is one of its clinical classification criteria. The
      presence of lupus anticoagulant has been shown to be the most important serologic
      risk factor for developing complications of pregnancy. A combination of low-dose
      acetylsalicylic acid and heparin has shown significant benefits with regard to
      pregnancy outcomes and APS-related miscarriage. Some congenital thrombophilic
      disorders also have an increased associated risk of developing RSA, although the
      risk is lower than for APS. The current analysis does not sufficiently support
      the analogous administration of heparin as prophylaxis against miscarriage in
      women with congenital thrombophilia in the same way as it is used in
      antiphospholipid syndrome. The data on rare, combined or homozygous
      thrombophilias and their impact on RSA are still insufficient. Conclusion: In
      contrast to antiphospholipid syndrome, the current data from studies on recurrent
      spontaneous abortion do not support the prophylactic administration of heparin to
      treat women with maternal hereditary thrombophilia in subsequent pregnancies.
      Nevertheless, the maternal risk of thromboembolic events must determine the
      indication for thrombosis prophylaxis in pregnancy.

PMID- 29576634
TI  - Psst, Can You Keep a Secret?
AB  - The security of encrypted data depends not only on the theoretical properties of
      cryptographic primitives but also on the robustness of their implementations in
      software and hardware. Threshold cryptography introduces a computational paradigm
      that enables higher assurance for such implementations.

PMID- 29576635
TI  - Rejection of Manuscripts: Problems and Solutions.

PMID- 29576636
TI  - Drug-resistant Spinal Tuberculosis.
AB  - Drug-resistant spinal tuberculosis (TB) is an emerging health problem in both
      developing and developed countries. In this review article, we aim to define
      management protocols for suspicion, diagnosis, and treatment of such patients.
      Spinal TB is a deep-seated paucibacillary lesion, and the demonstration of acid
      fast bacilli on Ziehl-Neelsen staining is possible only in 10%-30% of cases. Drug
      resistance is suspected in patients showing the failure of clinicoradiological
      improvement or appearance of a fresh lesion of osteoarticular TB while on anti
      tubercular therapy (ATT) for a minimum period of 5 months. The conventional
      culture of Mycobacterium tuberculosis remains the gold standard for both
      bacteriological diagnosis and drug sensitivity testing (DST); however, the high
      turn around time of 2-6 weeks for detection with added 3 weeks for DST is a major
      limitation. To overcome this problem, rapid culture methods and molecular methods
      have been introduced. From a public health perspective, reducing the period
      between diagnosis and treatment initiation has direct benefits for both the
      patient and the community. For all patients of drug-resistant spinal TB, a
      complete Drug-O-Gram should be prepared which includes details of all drugs,
      their doses, and duration. Patients with confirmed multidrug-resistant TB strains
      should receive a regimen with at least five effective drugs, including
      pyrazinamide and one injectable. Patients with resistance to additional
      antitubercular drugs should receive individualized ATT as per their DST results.

PMID- 29576637
TI  - Complications Associated with Locking Plate of Proximal Humerus Fractures.
AB  - Proximal humerus fractures constitute a significant percentage of fragility
      fractures. The growing use of locking plate has helped treat this problem, but at
      the same time has brought about complications. Past systematic reviews have
      documented these complications, however a large number of recent studies have
      been published since, reporting their own complication rates with different
      techniques. This study reviews the current complications associated with locking
      plate of proximal humerus fractures as well as methods to reduce them. A
      systematic review, following the PRISMA guidelines, was conducted in November
      2013 and repeated in March 2015, using PubMed, Scopus, and Cochrane databases, to
      evaluate locking plate fixation (and complications) of traumatic proximal humerus
      fractures. Inclusion criteria included adults (>18 years), minimum of 12-month
      postoperative followup, articles within the last 5 years, and studies with >10
      participants. Exclusion criteria included pathologic fractures, cadaveric
      studies, and nonhuman subjects. Eligible studies were graded using a quality
      scoring system. Articles with a minimum of 7/10 score were included and assessed
      regarding their level of evidence per the Journal of Bone and Joint Surgery and
      Centre for Evidence-Based Medicine guidelines. The initial query identified
      51,206 articles from multiple databases. These records were thoroughly screened
      and resulted in 57 articles, consisting of seven Level 1, three Level 2, 10 Level
      3, and 37 Level 4 studies, totaling 3422 proximal humerus fractures treated with
      locking plates. Intraarticular screw penetration was the most reported
      complication (9.5%), followed by varus collapse (6.8%), subacromial impingement
      (5.0%), avascular necrosis (4.6%), adhesive capsulitis (4.0%), nonunion (1.5%),
      and deep infection (1.4%). Reoperation occurred at a rate of 13.8%. Collapse at
      the fracture site contributed to a majority of the implant-related complications,
      which in turn were the main reasons for reoperation. The authors of these studies
      discussed different techniques that could be used to address these issues.
      Expanding use of locking plate in the proximal humerus fractures leads to
      improvements and advancements in surgical technique. Further research is
      necessary to outline indications to decrease complications, further.

PMID- 29576638
TI  - Is Combined Administration of Tranexamic Acid Better than Both Intravenous and
      Topical Regimes for Total Loss, Hidden Loss and Post-operative Swelling? A
      Randomized Control Trial.
AB  - Background: Bleeding is one of the unavoidable complications of total knee
      arthroplasty (TKA). Tranexamic acid (TXA) in last decade has emerged as an
      effective and safe way to decrease postoperative bleeding and transfusion rates.
      Although there is little doubt on the efficacy of the drug, the debate on ideal
      mode is more recent. We undertook this study to find out the most effective and
      yet safest way of TXA administration. Materials and Methods: A single institution
      - two hospital-based, double-blinded, prospective, randomized control trial was
      conducted from January 2015 to December 2015. One hundred and fifty patients were
      randomly divided in one of the three groups using computer-generated tables -
      intravenous (IV), intraarticular and combined. Evident loss through drain, total
      loss based on gross method and hemoglobin balance method, hidden blood losses,
      hemoglobin, and hematocrit drop, all possible complications related to TXA were
      evaluated and compared among groups. The analysis of variance and Tukey's post
      hoc were used for continuous outcome variables and Chi-square test for binary
      outcome variables. Results: Evident loss in combined group was 574.25 +/- 209.8
      ml, significantly less than IV (685.4 +/- 289.9 ml) and intraarticular group
      (724.3 +/- 246.8 ml). Total loss was similarly least for combined group (930.1 +/
      262.2 ml) compared to IV (1208.3 +/- 368.8 ml) and intraarticular group (1198.1
      +/- 356.8 ml). There were no transfusions in combined group compared to five in
      IV and four in intraarticular group. Combined group also had least hidden losses
      after surgery. No patients in any group developed symptomatic deep venous
      thrombosis. Conclusion: Combined administration of drug is most effective way to
      decrease postoperative bleeding and requirement of transfusion in unilateral TKA
      without increasing any risk of complications.

PMID- 29576639
TI  - Total Hip Arthroplasty by the Direct Anterior Approach Using a Neck-preserving
      Stem: Safety, efficacy and learning curve.
AB  - Background: The concept of femoral neck preservation in total hip replacement
      (THR) was introduced in 1993. It is postulated that retaining cortical bone of
      the femoral neck offers triplanar stability, uniform stress distribution, and
      accommodates physiological anteversion. However, data on safety, efficacy and
      learning curve are lacking. Materials and Methods: We prospectively assessed all
      patients who were operated for a THR with a short neck preserving stem (MiniHip)
      between 2012 and 2014. The safety and learning curve were assessed by recording
      operative time; stem size; and adverse events including periprosthetic fracture;
      paresthesia; and limb length discrepancy (LLD). The cohort was divided into equal
      groups to assess the learning curve effect, and the cumulative sums (CUSUM) test
      was performed to monitor intraoperative neck fractures. For assessment of
      efficacy, Oxford Hip Score (OHS) and Short Form-36 (SF-36) scores were compared
      preoperatively and postoperatively. Results: 138 patients with median age 62
      years (range 35-82 years) were included with a median followup of 42 months
      (range 30-56 months). The minimum followup was 2.5 years. The OHS, SF-36
      (physical and mental component) scores improved by a mean score of 26, 28, and 27
      points, respectively. All patients had LLD of <10 mm (1.9 mm +/- 1.3). Adverse
      events included intraoperative neck fracture (n = 6), subsidence (n = 1),
      periprosthetic fracture (n = 1), paresthesia (n = 12), and trochanteric bursitis
      (n = 2). After early modification of the technique to use a smaller finishing
      broach, the CUSUM test demonstrated acceptable intraoperative neck fracture risk.
      The second surgery group had a reduced risk of intraoperative neck fracture (5/69
      vs. 1/69 P = 0.2), reduced operative time (66 vs. 61 min, P = 0.06), and
      increased stem size (5 vs. 6, P = 0.09) although these differences were not
      statistically significant. Conclusions: The MiniHip stem is safe alternative to
      standard THR with good functional outcomes but with a learning curve for the
      surgical technique, implants sizing, and the risk of intraoperative neck
      fractures.

PMID- 29576640
TI  - Short Term Outcome of Varus Derotation Osteotomy in Late Presenting Perthes
      Disease.
AB  - Background: Untreated Perthes disease can lead to osteoarthritis by the fourth
      decade. The treatment is conservative for children <6 years, operative within the
      age group of 6-9 years. Late onset Perthes, older than 9 years or more, are
      notorious with the aggressive course with poor outcome. However, literature do
      not come to a consensus between conservative and operative management. This study
      evaluates the clinical and radiological outcome of varus derotation osteotomy
      (VDRO) in Perthes disease presenting late with age 8 years or more. Materials and
      Methods: 15 children (13 males and 2 females) with the mean age of 9.4 years
      belonging to modified Elizabethtown classification Stage IB, IIA, IIB treated
      with open wedge VDRO between 2008 and 2014 were included in this study. Seven
      patients (46.67%) were of >10 years of age at presentation. All patients had
      limitation of abduction and internal rotation. Eight patients (53.33%) had pain
      at the hip and 12 patients (80%) had limp. Mean time between diagnosis and
      corrective surgery was 3 weeks. Results: The evaluation was done using caput
      index (CI) and epiphyseal quotient (EQ) and articulotrochanteric distance
      radiologically, range of motion and Harris Hip Score for clinical outcome. All
      the measurements were carried out on pre- and postoperative X-rays after 3 years
      followup and compared with the contralateral normal hip. After a mean followup
      period of 3.4 years, we noted the statistically significant difference between
      pre- and postoperative values. We noted that all (100%) children in Stage IB, IIA
      and 50% children in Stage IIB achieved satisfactory results. There was a
      significant change (P = 0.000) in CI among all the patients after surgery. The
      final EQ after 3 years of VDRO was 0.606 and was significant (P = 0.0000).
      Conclusion: In our opinion, based on the encouraging short term radiological and
      clinical outcomes, VDRO may be regarded as a treatment procedure for late
      presenting Perthes disease in stage IB, IIA, IIB.

PMID- 29576641
TI  - Epidemiological Profile of Femoral Head Osteonecrosis in the North Indian
      Population.
AB  - Background: There are limited studies on the epidemiology of femoral head
      osteonecrosis in Indian population. This study was designed to look for the risk
      factors of osteonecrosis hip and to assess the severity as per radiological
      staging (Association Research Circulation Osseous [ARCO]) and clinical score
      (Harris hip score [HHS]). Materials and Methods: 249 patients (382 hips) of
      osteonecrosis femoral head (ONFH) who were evaluated at our center between
      January 1, 2005, and June 30, 2013, were included in this retrospective study.
      The details of history, clinical examination, radiological grading, and HHS were
      entered into a proforma. Results: The mean age was 34.71 years (range 14-70
      years) and 70.28% (n=175) patients were between 20 and 40 years. Male to female
      ratio was 5:1. Bilateral ONFH was observed in 53.41% (n=133) patients. In
      atraumatic conditions, bilateral involvement was seen in 61.61% (130/211)
      patients. Steroid administration (37.3%, 93/249) was most commonly observed in
      the patients followed by idiopathic in 21.3% (53/249) patients, chronic alcohol
      consumption in 20.1% (50/249) patients, and trauma in 15.3% (38/249) patients.
      There were 48% (185/382) hips in ARCO Stage 2 followed by 33% (125/382) in Stage
      3 and 16% (61/382) in Stage 4. The mean HHS was 80.97 +/- 14.35 in unilateral
      ONFH. The mean HHS was 72.79 +/- 14.43 and 80.07 +/- 13.52 in more involved hip
      and in less involved hip, respectively, in bilateral ONFH. The ARCO staging had
      statistically significant correlation with HHS (Pearson's correlation coefficient
      r = -0.783, P < 0.01) in unilateral ONFH patients and more severely affected hip
      in bilateral (Pearson's correlation coefficient r = -0.654, P < 0.01) ONFH, but
      it did not show any association with less involved hip in bilateral cases.
      Conclusion: ONFH in the North Indian patients is a disease of young individuals
      with male predominance. Steroid intake is most commonly observed in these
      patients followed by idiopathic, chronic alcohol consumption, and trauma.

PMID- 29576642
TI  - Comparative Study for Evaluating Efficacy of Fascia Iliaca Compartment Block for
      Alleviating Pain of Positioning for Spinal Anesthesia in Patients with Hip and
      Proximal Femur Fractures.
AB  - Background: Patient positioning for performing spinal blockade causes severe pain
      in hip and femur fracture. Adequate pain relief before administrating spinal
      blockade will increase patient's cooperation. This study was done to assess
      analgesic effect of fascia iliaca compartment block (FICB) for positioning for
      spinal anesthesia. Materials and Methods: This was a randomized, double blind,
      controlled prospective study that included 100 patients of the American Society
      of Anesthesiologists physical statuses I to III, of either sex, between 30 and 90
      years, posted for hip or proximal femoral surgery, with visual analogue scale
      (VAS) >3 in preoperative period. The two groups were assigned randomly. In Group
      1, FICB was given half an hour before shifting the patients in operation theater
      with 30 ml of 0.25% ropivacaine, and in Group 2, sham block was given with 30 ml
      normal saline. Each group included 50 patients. Thirty minutes after FICB, spinal
      anesthesia was given and patients' vitals were monitored before and after block,
      at the time of positioning for spinal anesthesia, intraoperative and
      postoperative periods. Results: In Group 1, mean VAS before FICB was 8.02 which
      reduced to 2.28, which is statistically significant (P = 7.8813E-50), whereas in
      Group 2, mean VAS before sham block was 7.98 which reduced to 7.90, which is
      statistically nonsignificant (P = 0.6694). Mean total duration of analgesia in
      Group 1 was 428.3 min after spinal anesthesia, whereas in Group 2, mean total
      duration of analgesia was 240.1 min. Conclusion: FICB effectively provides
      analgesia for positioning for spinal anesthesia to patients in hip and proximal
      femur surgeries. It also provides analgesia in postoperative period without
      having significant alteration in the hemodynamic profile of patients.

PMID- 29576643
TI  - Total Knee Arthroplasty Using Patient-specific Blocks after Prior Femoral
      Fracture without Hardware Removal.
AB  - Background: The options to perform total knee arthroplasty (TKA) with retained
      hardware in femur are mainly - removal of hardware, use of extramedullary guide,
      or computer-assisted surgery. Patient-specific blocks (PSBs) have been introduced
      with many potential advantages, but their use in retained hardware has not been
      adequately explored. The purpose of the present study was to outline and assess
      the usefulness of the PSBs in performing TKA in patients with retained femoral
      hardware. Materials and. Materials and Methods: Nine patients with retained
      femoral hardware underwent TKA using PSBs. All the surgeries were performed by
      the same surgeon using same implants. Nine cases (7 males and 2 females) out of
      total of 120 primary TKA had retained hardware. The average age of the patients
      was 60.55 years. The retained hardware were 6 patients with nails, 2 with plates
      and one patient had screws. Out of the nine cases, only one patient needed
      removal of a screw which was hindering placement of pin for the PSB. Results: All
      the patients had significant improvement in their Knee Society Score (KSS) which
      improved from 47.0 to postoperative KSS of 86.77 (P < 0.00). The mechanical axis
      was significantly improved (P < 0.03) after surgery. No patient required blood
      transfusion and the average tourniquet time was 41 min. Conclusion: TKA using
      PSBs is useful and can be used in patients with retained hardware with good
      functional and radiological outcome.

PMID- 29576644
TI  - Complex Tibial Plateau Fractures Treated by Hybrid External Fixation System: A
      correlation of followup computed tomography derived quality of reduction with
      clinical results.
AB  - Background: Tibial plateau fractures are common due to high energy injuries. The
      principles of treatment include respect for the soft tissues, restoring the
      congruity of the articular surface and reduction of the anatomic alignment of the
      lower limb to enable early movement of the knee joint. There are various surgical
      fixation methods that can achieve these principles of treatment. Recognition of
      the particular fracture pattern is important, as this guides the surgical
      approach required in order to adequately stabilize the fracture. This study
      evaluates the results of the combined treatment of external fixator and limited
      internal fixation along with the advantages using postoperative computed
      tomography (CT) scan after implant removal. Materials and. Methods: 55 patients
      with a mean age of 42 years (range 17-65 years) with tibial plateau fracture,
      were managed in our institution between October 2010 and September 2013., Twenty
      fractures were classified as Schatzker VI and 35 as Schatzker V. There were 8
      open fractures (2 Gustilo Anderson 3A and 6 Gustilo Anderson 2). All fractures
      were treated with closed reduction and hybrid external fixation (n = 21/38.2%) or
      with minimal open reduction internal fixation and a hybrid system (n = 34/61.8%).
      After the removal of the fixators, CT-scan was programmed for all the cases, for
      correlation with the results. At final followup, the American Knee Society Score
      (AKSS) was administered. Results: All patients were evaluated with a minimum of
      12 months (range 12-21 months) followup. Average time to union was 15.5 weeks
      (range 13-19 weeks). The postoperative joint congruity as evaluated in the
      postoperative CT-scan was <2 mm of articular step-off in 8 patients (14.5%),
      between 2 and 4 mm in 18 patients (32.7%) and over 4 mm in 29 (52.7%). The
      injured limb mechanical axis was restored within 5 degrees  compared to the
      contralateral limb in 36 cases (65%) and with an angulation >5 degrees  in 19
      cases (35%). Patients with residual joint depression <3.5 mm had a 95% chance of
      having excellent AKSS knee score results and 80% chance of having excellent AKSS
      function scores. On the other hand, residual joint depression of >4.5 mm
      displayed a 100% chance of getting poor-fair scores both in AKSS knee and AKSS
      function score. The association of a postoperative mechanical axis within 5
      degrees  of the contralateral limb and improved knee scores was statistically
      significant for the AKSS function and total scores but not for the AKSS knee
      score. The AKSS was negatively correlated with postoperative joint depression
      magnitude which was statistically significant. Only the amount of joint collapse
      was verified as a prognostic factor in a multivariate logistic regression
      analysis. Conclusions: The postoperative CT-scan shows important information
      about bone healing, and an exact image of the reduction and the shaft alignment.
      Postoperative radiographs may have led to an underestimation of the degree of
      residual displacement. On the contrary, CT-scan demonstrates the exact grade of
      articular displacement and depending on CT-scan results one can better manage the
      postoperative rehabilitation.

PMID- 29576645
TI  - Anterior Cruciate Ligament Reconstruction with Tibial Attachment Preserving
      Hamstring Graft without Implant on Tibial Side.
AB  - Background: Tibial attachment preserving hamstring graft could prevent potential
      problems of free graft in anterior cruciate ligament (ACL) reconstruction such as
      pull out before graft-tunnel healing or rupture before ligamentization. Different
      implants have been reportedly used for tibial side fixation with this technique.
      We investigated short-term outcome of ACL reconstruction (ACLR) with tibial
      attachment sparing hamstring graft without implant on the tibial side by outside
      in technique. Materials and Methods: Seventy nine consecutive cases of ACL tear
      having age of 25.7 +/- 6.8 years were included after Institutional Board
      Approval. All subjects were male. The mean time interval from injury to surgery
      was of 7.5 +/- 6.4 months. Hamstring tendons were harvested with open tendon
      stripper leaving the tibial insertion intact. The free ends of the tendons were
      whip stitched, quadrupled, and whip stitched again over the insertion site of
      hamstring with fiber wire (Arthrex). Single bundle ACLR was done by outside in
      technique and the femoral tunnel was created with cannulated reamer. The graft
      was pulled up to the external aperture of femoral tunnel and fixed with
      interference screw (Arthrex). The scoring was done by Lysholm, Tegner, and KT
      1000 by independent observers. All cases were followed up for 2 years. Results:
      The mean length of quadrupled graft attached to tibia was 127.65 +/- 7.5 mm, and
      the mean width was 7.52 +/- 0.78 mm. The mean preoperative Lysholm score of 47.15
      +/- 9.6, improved to 96.8 +/- 2.4 at 1 year. All cases except two returned to the
      previous level of activity after ACLR. There was no significant difference
      statistically between preinjury (5.89 +/- 0.68) and postoperative (5.87 +/- 0.67)
      Tegner score. The anterior tibial translation (ATT) (KT 1000) improved from 11.44
      +/- 1.93 mm to 3.59 +/- 0.89 mm. The ATT of operated knee returned to nearly the
      similar value as of the opposite knee (3.47 +/- 1.16 mm). The Pivot shift test
      was negative in all cases. None had a failure of graft till final followup.
      Conclusion: Attachment sparing hamstring graft without a tibial implant is a
      simple, cost-effective technique that provides a consistently satisfactory
      outcome.

PMID- 29576646
TI  - Sloppy Hinge Prosthetic Replacement in Old Healed Side Swipe Injuries of Elbow -
      Long term Results.
AB  - Background: Sideswipe injuries of elbow often poses significant functional loss
      resulting from devastating injuries involving osseoligamentous structures as well
      as multilevel soft tissue injuries around the elbow. Inspite of treatment, no
      conscientious treatment opinion is available in the literature to provide optimum
      functional outcome. The objective of this study is to evaluate the results of
      prosthetic replacement of old healed sideswipe injuries of elbow with gross
      dysfunctional disabilities resulting from loss of bones and muscles around the
      joint. Materials and Methods: Fourteen patients of 2-3 years old healed sideswipe
      injuries of the elbow, treated by Baksi sloppy hinge (original version in seven
      and recent version in seven) prosthetic replacement were evaluated. All had
      normal neurovascular status except two; one having ulnar nerve deficit the other
      median nerve in another. The mean age was 42.7 years (range 32-61 years).
      Results: The average followup period was 13.5 years (range 5.11-23.11 years). Ten
      patients regained stable 0 degrees  to 130 degrees  elbow flexion, and four had
      restricted terminal flexion with arc 10 degrees -115 degrees  following V-Y
      plasty of contracted triceps. Mean supination was 22 degrees  and mean pronation
      was 35 degrees . According to Mayo Elbow Performance Score (MEPS), excellent
      results were in five (35.7%), good in six (42.8%), and fair in one (7.1%). Two
      patients (14.2%) needed removal of prosthesis due to intractable delayed
      infection and considered failure. Following removal, the resected elbow retained
      relatively stable motions due to mature fibrous tissues connecting the adjacent
      bone ends and reorientation of muscle balance. Postoperative improvement of MEPS
      (mean 84) was significant (P = 0.0037) compared to preoperative value (mean
      41.7). Two patients had superficial wound infection and five aseptic loosening of
      which one was symptomatic. Conclusion: Prosthetic replacement of elbow is an
      effective salvage procedure in old healed sideswipe injuries.

PMID- 29576647
TI  - A Scoring System to Demonstrate the Risk for Bone Injury in Patients with
      Clinically Suspected or Occult Scaphoid Fracture.
AB  - Background: It is important to diagnose a scaphoid fracture accurately and start
      the correct treatment in the shortest time possible. However, the fracture of
      bone may not be visible on x-ray. In such cases, patients are clinically
      diagnosed with suspected or occult scaphoid fractures. The aim of this study was
      to define a scoring system based on physical examination to demonstrate the risk
      for bone injury in patients with clinically suspected and occult scaphoid
      fractures with negative radiographs and anatomical snuff box tenderness and to
      decrease the costs and workforce loss due to unnecessary treatment and magnetic
      resonance imaging (MRI). Materials and Methods: Patients were initially evaluated
      by the attendant orthopedic physician in the emergency service with X-ray of the
      wrist, and ten wrist physical examination techniques were used. The X-rays of
      patients were evaluated by three orthopedic surgeons. Finally sixty patients, who
      were diagnosed as having no fracture by all three orthopedic surgeon, were
      included in the study. The wrists of these patients were evaluated with MRI.
      Results: There were 46 male (77%) and 14 female (23%) patients with a mean age of
      21.5 years (range 7-61 years). About 3.3% had triquetrum fracture, 15% had bone
      edema in the scaphoid and radius, 18.3% had distal radius fracture, 31.6% had
      scaphoid fracture, and 31.8% had no bone injury. A scoring system was also
      proposed. It can be predicted that in the physical examination of the wrist if
      the total score is higher than 6.5, the probability of fracture is 2.87 (positive
      likelihood ratio) fold compared to scores below 6.5. Conclusions: Proposal of
      this new scoring system was thought to be useful for predicting the risk for bone
      injury in patients with clinically suspected scaphoid fractures and making
      decision regarding therapeutic options.

PMID- 29576648
TI  - Sagittal Atlantoaxial Joint Inclination and Reduction Index Values for Diagnosis
      and Treatment of Irreducible Atlantoaxial Dislocation.
AB  - Background: Irreducible atlantoaxial dislocation (IAAD) is a disorder of
      atlantoaxial joint instability with various causes. The diagnostic criteria for
      IAAD are variable. The diagnosis of IAAD is mainly based on preoperative and
      intraoperative traction results, as well as the physician's experience, with no
      relatively uniform guidelines for the selection of treatment. This study
      evaluates sagittal atlantoaxial joint inclination (SAAJI) and reduction index
      (RI) values for diagnosis and treatment of IAAD. Materials and Methods: 24 IAAD
      patients treated in our hospital from January 2008 to July 2014 were
      retrospectively analysed. Patients included were 13 males and 11 females, with a
      mean age of 43 years. The various causes for IAAD were atlantoaxial transverse
      ligament rupture (n=3), old dens fracture (n=15), occipitalization of the atlas
      (n=6). The patients were divided into two groups. group A underwent anterior
      release with posterior reduction and fixation; Group B underwent posterior
      reduction and fixation; 12 healthy individuals served as controls. SAAJI and
      atlas-dens interval (ADI) values before and after traction were measured, and RI
      was calculated. Imaging data were analyzed. Results: The mean SAAJI values were
      as follows: left, 5.6 +/- 1.9 degrees  and right, 5.1 +/- 2.1 degrees  in the
      control group; right, 39.5 +/- 6.0 degrees  and left, 38.8 +/- 5.8 degrees  in
      Group A; and right, 23.1 +/- 7.0 degrees  and left, 23.9 +/- 6.1 degrees  in
      Group B. There was no significant difference in the SAAJI values of the three
      groups (P < 0.05). The mean RIs in Groups A and B were 17.6 +/- 9.3% and 34.4 +/-
      5.2%, respectively, and the difference was statistically significant (P < 0.05).
      There were obvious negative correlations between the SAAJI and RI values in
      Groups A and B. Conclusions: SAAJI and RI can be used as important imaging
      indicators to determine the reversibility of IAAD. If the RI value is >27.9% and
      SAAJI value is <32.5 degrees , reduction and fixation can be achieved by the
      posterior approach alone; otherwise, a combination of anterior and posterior
      approaches would be necessary.

PMID- 29576649
TI  - Error Analysis: How Precise is Fused Deposition Modeling in Fabrication of Bone
      Models in Comparison to the Parent Bones?
AB  - Background: Rapid prototyping (RP) is used widely in dental and faciomaxillary
      surgery with anecdotal uses in orthopedics. The purview of RP in orthopedics is
      vast. However, there is no error analysis reported in the literature on bone
      models generated using office-based RP. This study evaluates the accuracy of
      fused deposition modeling (FDM) using standard tessellation language (STL) files
      and errors generated during the fabrication of bone models. Materials and
      Methods: Nine dry bones were selected and were computed tomography (CT) scanned.
      STL files were procured from the CT scans and three-dimensional (3D) models of
      the bones were printed using our in-house FDM based 3D printer using
      Acrylonitrile Butadiene Styrene (ABS) filament. Measurements were made on the
      bone and 3D models according to data collection procedures for forensic skeletal
      material. Statistical analysis was performed to establish interobserver co
      relation for measurements on dry bones and the 3D bone models. Statistical
      analysis was performed using SPSS version 13.0 software to analyze the collected
      data. Results: The inter-observer reliability was established using intra-class
      coefficient for both the dry bones and the 3D models. The mean of absolute
      difference is 0.4 that is very minimal. The 3D models are comparable to the dry
      bones. Conclusions: STL file dependent FDM using ABS material produces near
      anatomical 3D models. The high 3D accuracy hold a promise in the clinical
      scenario for preoperative planning, mock surgery, and choice of implants and
      prostheses, especially in complicated acetabular trauma and complex hip
      surgeries.

PMID- 29576650
TI  - Histological Observation of the Retinacula of Weitbrecht and Its Clinical
      Significance: A cadaveric study.
AB  - Background: The retinacular arteries provide major supply to the femoral head,
      their injuries may lead to the femoral head necrosis (FHN) in femoral neck
      fractures. Although the femoral neck fracture was seriously displaced in some
      patients, FHN did not occur, which suggests that the blood supply is not fully
      blocked. This study was aimed to find the association between the structure of
      the retinacula of Weitbrecht and the mechanism of protecting retinacular arteries
      from being injured. Materials and Methods: Fourteen formalin-fixed cadaveric
      specimens (in 28 hips) with no significant vascular disease were observed. The
      retinacula were cut longitudinally and then cut into three parts: medial, middle,
      and lateral. These specimens were stained using hematoxylin and eosin and
      improved Masson Trichrome stain. The microstructure and tightness of the
      retinacula fixed to the bone and the distribution of vessels were examined under
      a stereoscope, an optical microscope, and a scanning electron microscope.
      Results: The microstructure and compactness in each part of retinacula were
      different, and the tightness of the fibers of the retinacula fixed to the bone in
      each part were different. A particular structure which resembled a Sandwich
      panels was observed, and it may be an effective mechanism of protecting
      retinacular arteries. Conclusion: The Sandwich panels structure existed generally
      in the retinacula of Weitbrecht, and this sandwich panelture may play very
      important role in protecting the retinaculum artery from being injured, which
      show the importance of protecting the retinacular artery in the treatment of
      femoral neck fractures.

PMID- 29576651
TI  - Surgical Treatment of Sanders Type 2 Calcaneal Fractures Using a Sinus Tarsi
      Approach.

PMID- 29576652
TI  - Author's reply.

PMID- 29576653
TI  - Making the Surgeons Safe in India.

PMID- 29576654
TI  - Legends of Indian Orthopedics: Pramod Karan Sethi.

PMID- 29576655
TI  - Encountering energy precarity: Geographies of fuel poverty among young adults in
      the UK.
AB  - This paper develops the notion of "energy precarity" in order to uncover the
      governance practices and material conditions that drive and reproduce the
      inability of households to secure socially- and materially-necessitated levels of
      energy services in the home. The overarching aim is to foreground a geographical
      approach towards the study of domestic energy deprivation, by emphasizing the
      complex socio-spatial and material embeddedness of fuel poverty. The paper
      operationalizes these ideas via a field-based study of a group that has received
      limited attention in research and policy on fuel poverty: young adults living in
      privately rented accommodation. In evoking the experiences of such individuals, I
      employ energy precarity as a means of unpacking the spaces where energy
      deprivation is produced, experienced and contested. Among other findings, I
      highlight that people's fluid lifestyles and specific end-use energy demand
      patterns mean that energy deprivation metaphorically and physically overflows the
      limits of home, creating multiple performativities of precarity that have
      received very little attention to date.

PMID- 29576657
TI  - The Economic Organization of Extended Family Households by Race/Ethnicity and
      Socioeconomic Status.
AB  - This study examines differences in the amount of economic support or mutual
      benefit derived from extended family living arrangements by studying differences
      in monetary contributions to essential household expenditures across family units
      in extended family households. Using the 2008 Survey of Income and Program
      Participation, multivariate regression and selection models are estimated to
      assess racial differences in family contributions toward household expenses in
      extended family households. Extended family households have very unequal monetary
      contributions towards household rent and utilities, although Hispanics have less
      unequal monetary contributions compared to other racial groups. Hispanic and
      Asians extended family households experience decreasing inequality in financial
      contributions as the income of each family increases whereas no relationship
      between financial contributions and income is found for whites or blacks. This
      suggests a different cultural orientation to extended family living arrangements
      for Asians and Hispanics compared to non-Hispanic whites.

PMID- 29576656
TI  - Desire for and to Avoid Pregnancy during the Transition to Adulthood.
AB  - Unintended pregnancies disproportionately occur among teenage women, yet little
      is known about the determinants of pregnancy desire among this group. We use a
      comprehensive baseline survey and weekly data on pregnancy desires to investigate
      which unmarried 18-20 year-old women want a pregnancy, want to avoid pregnancy,
      and report consistent pregnancy desire and disinclination. Variables that
      positively predict pregnancy desire generally negatively predict desire to avoid
      pregnancy. While most young women have no desire and strong disinclination in
      most weeks, childhood receipt of public assistance is a strong predictor of
      wanting pregnancy and not wanting to avoid it. Comparing nested models suggests
      that the effects of childhood disadvantage operate through social environments
      where early pregnancy is less stigmatized. Young women in serious relationships,
      who are depressed, and who are not pursuing post-secondary education have more
      desire for pregnancy and less disinclination, but little of childhood
      disadvantage is mediated by these factors.

PMID- 29576658
TI  - Insights in the determination of saxitoxin with fluorogenic crown ethers in
      water.
AB  - Abstract: In this contribution, we present new insights and a critical discussion
      in the optical detection of saxitoxin using fluorophores with crown ethers.
      Fluorescence enhancement is caused by the reduction of photoinduced electron
      transfer upon complexation with the analyte. Our attempts to improve this
      detection method neither did yield a functioning sensor nor were the attempts to
      reproduce published data in this area successful. Due to the fact that only low
      concentrations of saxitoxin are available, multiple surrogates were investigated
      at high concentrations. However, no turn on response was observed. Moreover, a
      fluorescent decomposition product of saxitoxin that forms under UV light was
      discovered which was in our opinion misinterpreted as a sensor response by
      previous publications. Graphical abstract: 

PMID- 29576659
TI  - Benzil/triethylamine: a photo-reducing system for Cu2.
AB  - Abstract: We have investigated the photo-induced reduction of Cu2+-Cu0 using
      benzil/triethylamine mixtures. The formation of elemental Cu is indicated by the
      appearance of its characteristic plasmon absorption peaks at 515 nm and 620 nm.
      Importantly, the nature of the counterion of the Cu2+ salt affects the reduction
      process. In the presence of Cl-, the reduction proceeds faster than with SO42-.
      Photo-induced electron transfer between excited benzil and triethylamine leads to
      the benzil radical anion, which acts as the reducing agent for Cu2+ and generates
      Cu0. Graphical abstract: 

PMID- 29576660
TI  - MOTHERS' AND FATHERS' PARENTING PRACTICES WITH THEIR DAUGTERS AND SONS IN LOW-
      AND MIDDLE-INCOME COUNTRIES.

PMID- 29576661
TI  - The potential of achiral sponge-derived and synthetic bromoindoles as selective
      cytotoxins against PANC-1 tumor cells.
AB  - Our quest to isolate and characterize natural products with in vitro solid tumor
      selectivity is driven by access to repositories of Indo-Pacific sponge extracts.
      In this project an extract of a species of Haplosclerida sponge obtained from the
      US NCI Natural Products Repository displayed, by in vitro disk diffusion assay
      (DDA) and IC50 determinations, selective cytotoxicity with modest potency to a
      human pancreatic cancer cell line (PANC-1) relative to the human lymphoblast
      leukemia cell line (CCRF-CEM). Two brominated indoles, the known 6-bromo
      conicamin (1) and the new derivative, 6-Br-8-keto-conicamin A (2), were
      identified and 2 (IC50 1.5 MUM for the natural product vs 4.1 MUM for the
      synthetic material) was determined to be responsible for the cytotoxic activity
      of the extract against the PANC-1 tumor cell line. The new natural product and
      ten additional analogs were prepared for further SAR testing.

PMID- 29576662
TI  - Situating Green Infrastructure in Context: A Framework for Adaptive Socio
      Hydrology in Cities.
AB  - Management of urban hydrologic processes using green infrastructure (GI) has
      largely focused on stormwater management. Thus, design and implementation of GI
      usually rely on physical site characteristics and local rainfall patterns, and do
      not typically account for human or social dimensions. This traditional approach
      leads to highly centralized stormwater management in a disconnected urban
      landscape, and can deemphasize additional benefits that GI offers, such as
      increased property value, greenspace aesthetics, heat island amelioration, carbon
      sequestration, and habitat for biodiversity. We propose a Framework for Adaptive
      Socio-Hydrology (FrASH) in which GI planning and implementation moves from a
      purely hydrology-driven perspective to an integrated socio-hydrological approach.
      This allows for an iterative, multifaceted decision-making process that would
      enable a network of stakeholders to collaboratively set a dynamic, context-guided
      project plan for the installation of GI, rather than a 'one-size-fits-all'
      installation. We explain how different sectors (e.g., governance, non
      governmental organizations, academia, and industry) can create a connected
      network of organizations that work towards a common goal. Through a graphical
      Chambered Nautilus model, FrASH is experimentally applied to contrasting GI case
      studies and shows that this multi-stakeholder, connected, de-centralized network
      with a co-evolving decision-making project plan results in enhanced multi
      functionality, potentially allowing for the management of resilience in urban
      systems at multiple scales.

PMID- 29576663
TI  - Governance and the effectiveness of public health subsidies: Evidence from Ghana,
      Kenya and Uganda.
AB  - Distributing subsidized health products through existing health infrastructure
      could substantially and cost-effectively improve health in sub-Saharan Africa.
      There is, however, widespread concern that poor governance - in particular,
      limited health worker accountability - seriously undermines the effectiveness of
      subsidy programs. We audit targeted bednet distribution programs to quantify the
      extent of agency problems. We find that around 80% of the eligible receive the
      subsidy as intended, and up to 15% of subsidies are leaked to ineligible people.
      Supplementing the program with simple financial or monitoring incentives for
      health workers does not improve performance further and is thus not cost
      effective in this context.

PMID- 29576664
TI  - GENETIC VARIABILITY OF MINERAL COMPOSITION IN COMMON BEAN SEED.
AB  - Common bean genotypes were grown in three different growing sites and analyzed
      for 17 mineral compositions. The influence of growing sites was observed on all
      seed mineral contents however, ratio of genotypic variance to genotype x
      environment variance indicated greater influence and stability of genetic factor
      on Ca and Sr. It was observed that the Zn concentration is highly correlated with
      S and Fe and Ca with Sr in common bean seed.

PMID- 29576665
TI  - In situ process monitoring in selective laser sintering using optical coherence
      tomography.
AB  - Selective laser sintering (SLS) is an efficient process in additive manufacturing
      that enables rapid part production from computer-based designs. However, SLS is
      limited by its notable lack of in-situ process monitoring when compared to other
      manufacturing processes. We report the incorporation of optical coherence
      tomography into an SLS system in detail and demonstrate access to surface and sub
      surface features. Video frame rate cross-sectional imaging reveals areas of
      sintering uniformity and areas of excessive heat error with high temporal
      resolution. We propose a set of image processing techniques for SLS process
      monitoring with OCT and report the limitations and obstacles for further OCT
      integration with SLS systems.

PMID- 29576666
TI  - Electron Crescent Distributions as a Manifestation of Diamagnetic Drift in an
      Electron-Scale Current Sheet: Magnetospheric Multiscale Observations Using New
      7.5 ms Fast Plasma Investigation Moments.
AB  - We report Magnetospheric Multiscale observations of electron pressure gradient
      electric fields near a magnetic reconnection diffusion region using a new
      technique for extracting 7.5 ms electron moments from the Fast Plasma
      Investigation. We find that the deviation of the perpendicular electron bulk
      velocity from E * B drift in the interval where the out-of-plane current density
      is increasing can be explained by the diamagnetic drift. In the interval where
      the out-of-plane current is transitioning to in-plane current, the electron
      momentum equation is not satisfied at 7.5 ms resolution.

PMID- 29576667
TI  - Multimodel Evidence for an Atmospheric Circulation Response to Arctic Sea Ice
      Loss in the CMIP5 Future Projections.
AB  - Previous single-model experiments have found that Arctic sea ice loss can
      influence the atmospheric circulation. To evaluate this process in a multimodel
      ensemble, a novel methodology is here presented and applied to infer the
      influence of Arctic sea ice loss in the CMIP5 future projections. Sea ice
      influence is estimated by comparing the circulation response in the RCP8.5
      scenario against the circulation response to sea surface warming and CO2 increase
      inferred from the AMIPFuture and AMIP4xCO2 experiments, where sea ice is
      unperturbed. Multimodel evidence of the impact of sea ice loss on midlatitude
      atmospheric circulation is identified in late winter (January-March), when the
      sea ice-related surface heat flux perturbation is largest. Sea ice loss acts to
      suppress the projected poleward shift of the North Atlantic jet, to increase
      surface pressure in northern Siberia, and to lower it in North America. These
      features are consistent with previous single-model studies, and the present
      results indicate that they are robust to model formulation.

PMID- 29576668
TI  - Urban Greenspace is Associated with Reduced Psychological Stress among
      Adolescents: A Geographic Ecological Momentary Assessment (GEMA) Analysis of
      Activity Space.
AB  - This study investigates the momentary association between urban greenspace,
      captured using Normalized Difference Vegetation Index (NDVI) derived from Landsat
      imagery, and psychological stress, captured using Geographic Ecological Momentary
      Assessment (GEMA), in the activity spaces of a sample of primarily African
      American adolescents residing in Richmond, Virginia. We employ generalized
      estimating equations (GEE) to estimate the effect of exposure to urban greenspace
      on stress and test for moderation by sex, emotional dysregulation, season,
      neighborhood disadvantage, and whether the observation occurs at home or
      elsewhere. Results indicate that urban greenspace is associated with lower stress
      when subjects are away from home, which we speculate is due to the properties of
      stress reduction and attention restoration associated with exposure to natural
      areas, and to the primacy of other family dynamics mechanisms of stress within
      the home. Subjects may also seek out urban greenspaces at times of lower stress
      or explicitly for purposes of stress reduction. The greenspace-stress association
      away from home did not differ by sex, emotional dysregulation, neighborhood
      disadvantage, or season, the latter of which suggests that the observed
      greenspace-stress relationship is associated with being in a natural environment
      rather than strictly exposure to abundant green vegetation. Given the association
      of urban greenspace with lower stress found here and in other studies, future
      research should address the mediated pathways between greenspace, stress, and
      stress-related negative health outcomes for different population subgroups as a
      means toward understanding and addressing health disparities.

PMID- 29576669
TI  - Parent-reported stigma and child anxiety: A mixed methods research study.
AB  - Background: Stigma has been frequently cited as a barrier to service use for
      various mental health problems. Studies suggest that stigma may be greater for
      childhood mental health problems that are perceived as more atypical. Aims: This
      study utilized a mixed methods research design (qual + QUAN) to examine parental
      endorsement of stigma and its impact on service utilization among children with
      significant anxiety-a common childhood problem frequently perceived as normative.
      Methods: Semi-structured qualitative interviews were conducted with 29 parents of
      anxious children. Qualitative data were coded using a grounded theory approach,
      and stigma-related responses were examined for emergent themes. Quantitative data
      was analyzed with frequency counts and chi-square analysis. Results: Stigma
      related to children's anxiety symptoms and seeking mental health services was
      reported by 41.3% (n = 12) of parents. Emergent themes included: 1) Parental
      Concern for Negative Consequences, 2) Parent Internalized Stigma, and 3) Negative
      Associations with Mental Health Treatment. Latino parents discussed stigma more
      frequently than non-Latino White parents (70% vs. 17.6%, respectively, X2(1, N =
      27) = 5.33, p < 0.05). Conclusions: Although anxiety is a common childhood
      problem, stigma is still frequently reported by parents and may be an important
      barrier to mental health service use, especially among Latino youth.

PMID- 29576670
TI  - Natural radioactivity in granites and gneisses of the Opava Mountains (Poland): a
      comparison between laboratory and in situ measurements.
AB  - The natural radioactivities of five characteristic igneous rocks of the eastern
      foreland of the Opava Mountains (Eastern Sudetes, Poland), obtained in the
      laboratory and under in situ conditions, are presented. The activity
      concentrations of 232Th, 238U, and 40K were measured using an HPGe gamma-ray
      spectrometry system. The ranges of the activity concentrations of 232Th were 7-71
      Bq kg-1 in the laboratory and 6-68 Bq kg-1 for the in situ measurements. For
      238U, the ranges of the activity concentrations were 5-52 Bq kg-1 in the
      laboratory and 9-48 Bq kg-1 for the in situ measurements, and for 40K, the ranges
      were 520-1560 Bq kg-1 in the laboratory and 537-1700 Bq kg-1 for the in situ
      measurements. These determined activity concentrations were compared with the
      average activity concentrations of the radionuclides in similar types of rocks
      and with data from the Sudetes available in the literature. No significant
      differences were found between the in situ and laboratory measurements.

PMID- 29576671
TI  - First identification and characterization of Borrobol-type tephra in the
      Greenland ice cores: new deposits and improved age estimates.
AB  - Contiguous sampling of ice spanning key intervals of the deglaciation from the
      Greenland ice cores of NGRIP, GRIP and NEEM has revealed three new silicic
      cryptotephra deposits that are geochemically similar to the well-known Borrobol
      Tephra (BT). The BT is complex and confounded by the younger closely timed and
      compositionally similar Penifiler Tephra (PT). Two of the deposits found in the
      ice are in Greenland Interstadial 1e (GI-1e) and an older deposit is found in
      Greenland Stadial 2.1 (GS-2.1). Until now, the BT was confined to GI-1-equivalent
      lacustrine sequences in the British Isles, Sweden and Germany, and our discovery
      in Greenland ice extends its distribution and geochemical composition. However,
      the two cryptotephras that fall within GI-1e ice cannot be separated on the basis
      of geochemistry and are dated to 14358 +/- 177 a b2k and 14252 +/- 173 a b2k,
      just 106 +/- 3 years apart. The older deposit is consistent with BT age estimates
      derived from Scottish sites, while the younger deposit overlaps with both BT and
      PT age estimates. We suggest that either the BT in Northern European terrestrial
      sequences represents an amalgamation of tephra from both of the GI-1e events
      identified in the ice-cores or that it relates to just one of the ice-core
      events. A firm correlation cannot be established at present due to their strong
      geochemical similarities. The older tephra horizon, found within all three ice
      cores and dated to 17326 +/- 319 a b2k, can be correlated to a known layer within
      marine sediment cores from the North Iceland Shelf (ca. 17179-16754 cal a BP).
      Despite showing similarities to the BT, this deposit can be distinguished on the
      basis of lower CaO and TiO2 and is a valuable new tie-point that could eventually
      be used in high-resolution marine records to compare the climate signals from the
      ocean and atmosphere.

PMID- 29576672
TI  - Cumulative stress restricts niche filling potential of habitat-forming kelps in a
      future climate.
AB  - Climate change is driving range contractions and local population extinctions
      across the globe. When this affects ecosystem engineers the vacant niches left
      behind are likely to alter the wider ecosystem unless a similar species can
      fulfil them.Here, we explore the stress physiology of two coexisting kelps
      undergoing opposing range shifts in the Northeast Atlantic and discuss what
      differences in stress physiology may mean for future niche filling.We used
      chlorophyll florescence (Fv/Fm) and differentiation of the heat shock response
      (HSR) to determine the capacity of the expanding kelp, Laminaria ochroleuca, to
      move into the higher shore position of the retreating kelp, Laminaria digitata.
      We applied both single and consecutive exposures to immersed and emersed high and
      low temperature treatments, replicating low tide exposures experienced in summer
      and winter.No interspecific differences in HSR were observed which was surprising
      given the species' different biogeographic distributions. However, chlorophyll
      florescence revealed clear differences between species with L. ochroleuca better
      equipped to tolerate high immersed temperatures but showed little capacity to
      tolerate frosts or high emersion temperatures.Many patterns observed were only
      apparent after consecutive exposures. Such cumulative effects have largely been
      overlooked in tolerance experiments on intertidal organisms despite being more
      representative of the stress experienced in natural habitats. We therefore
      suggest future experiments incorporate consecutive stress into their
      design.Climate change is predicted to result in fewer ground frosts and increased
      summer temperatures. Therefore, L. ochroleuca may be released from its summer
      cold limit in winter but still be prevented from moving up the shore due to
      desiccation in the summer. Laminaria ochroleuca will, however, likely be able to
      move into tidal pools. Therefore, only partial niche filling by L. ochroleuca
      will be possible in this system as climate change advances. A plain language
      summary is available for this article.

PMID- 29576673
TI  - Trophic consequences of introduced species: Comparative impacts of increased
      interspecific versus intraspecific competitive interactions.
AB  - Invasive species can cause substantial ecological impacts on native biodiversity.
      While ecological theory attempts to explain the processes involved in the trophic
      integration of invaders into native food webs and their competitive impacts on
      resident species, results are equivocal. In addition, quantifying the relative
      strength of impacts from non-native species (interspecific competition) versus
      the release of native conspecifics (intraspecific competition) is important but
      rarely completed.Two model non-native fishes, the globally invasive Cyprinus
      carpio and Carassius auratus, and the model native fish Tinca tinca, were used in
      a pond experiment to test how increased intra- and interspecific competition
      influenced trophic niches and somatic growth rates. This was complemented by
      samples collected from three natural fish communities where the model fishes were
      present. The isotopic niche, calculated using stable isotope data, represented
      the trophic niche.The pond experiment used additive and substitutive treatments
      to quantify the trophic niche variation that resulted from intra- and
      interspecific competitive interactions. Although the trophic niche sizes of the
      model species were not significantly altered by any competitive treatment, they
      all resulted in patterns of interspecific niche divergence. Increased
      interspecific competition caused the trophic niche of T. tinca to shift to a
      significantly higher trophic position, whereas intraspecific competition caused
      its position to shift towards elevated delta13C. These patterns were independent
      of impacts on fish growth rates, which were only significantly altered when
      interspecific competition was elevated.In the natural fish communities, patterns
      of trophic niche partitioning between the model fishes was evident, with no niche
      sharing. Comparison of these results with those of the experiment revealed the
      most similar results between the two approaches were for the niche partitioning
      between sympatric T. tinca and C. carpio.These results indicate that trophic
      niche divergence facilitates the integration of introduced species into food
      webs, but there are differences in how this manifests between introductions that
      increase inter- and intraspecific competition. In entirety, these results suggest
      that the initial ecological response to an introduction appears to be a trophic
      re-organisation of the food web that minimises the trophic interactions between
      competing species. A plain language summary is available for this article.

PMID- 29576674
TI  - The Park is Ruining our Livelihoods. We Support the Park! Unravelling the Paradox
      of Attitudes to Protected Areas.
AB  - Despite considerable field-based innovation and academic scrutiny, the nexus
      between conservation approaches, local support for parks and park effectiveness
      remains quite puzzling. Common approaches to understanding notions of
      environmental justice are to understand distributional and procedural issues,
      representation in decision making, and recognition of authorities and claims. We
      took a different approach and analysed environmental justice claims through
      institutional, ideational and psychological lenses. We sought to understand how
      the national park could have such broad support from local communities despite
      their acknowledgement that it severely curtailed their livelihoods. We conducted
      100 household interviews in three villages that border Nam Et-Phou Louey National
      Protected Area. Our study found that villagers 1) hold on to broken promises by
      the State for agricultural activities and alternative revenues without fully
      changing forest use behaviours; 2) were influenced heavily by the 'educational'
      programmes by the State; 3) accepted the authority of the State and lack of
      participation in decision-making based on historical experiences and values; 4)
      justified their burdens by over-emphasising the positive aspects of the park. Our
      findings present a complementary framework to explain environmental justice
      claims, allowing for a nuanced analysis of how people respond to justices and
      injustices, and specifically how injustices can be identified through proven
      social science concepts.

PMID- 29576675
TI  - Brachythecium rutabulum, A Neglected Medicinal Moss.

PMID- 29576677
TI  - Discovery Orientation, Cognitive Schemas, and Disparities in Science Identity in
      Early Adolescence.
AB  - Why are some youth more likely to think of themselves as a science kind of person
      than others? In this paper, we use a cognitive social-theoretical framework to
      assess disparities in science identity among middle school-age youth in the
      United States. We investigate how discovery orientation is associated with
      science interest, perceived ability, importance, and reflected appraisal, and how
      they are related to whether youth see themselves, and perceive that others see
      them, as a science kind of person. We surveyed 441 students in an ethnically
      diverse, low-income middle school. Gender and race/ethnicity are associated with
      science identity but not with discovery orientation. Structural equation model
      results show that the positive association between discovery orientation and
      science identity is mediated by science interest, importance, and reflected
      appraisal. These findings advance understanding of how science attitudes and
      recognition may contribute to the underrepresentation of girls and/or minorities
      in science.

PMID- 29576678
TI  - Culture, Parenting, and Zero-to-Threes.
AB  - Perhaps the most important single thing that a parent does for a child is
      determine the culture into which that child is born. This essay addresses
      parenting, culture, and the intersection of the two. The study of parenting in
      culture is one of similarities and differences in parental cognitions and
      practices and their meaning. Illustrations are provided for each.

PMID- 29576679
TI  - Comparing Different Approaches for Subtyping Children with Conduct Problems:
      Callous-Unemotional Traits Only Versus the Multidimensional Psychopathy
      Construct.
AB  - The aim of this study was to compare two youth psychopathy models (i.e., callous
      unemotional versus multidimensional model) in their ability to predict future and
      stable conduct problems (CP). At baseline, mothers and fathers of 321 boys and
      369 girls (ages 7-12) completed measures that tap callous-unemotional and other
      psychopathic traits. Parent-reported CP was collected at baseline and at 6- and
      12 month follow-ups. Children were assigned to mutually exclusive groups based on
      their levels of CP and psychopathic traits. Children with CP who manifested
      callous-unemotional traits (Callous-Unemotional + CP) were occasionally at risk
      for future and stable CP. Yet, across gender, children with CP scoring high on
      all psychopathic trait dimensions (Psychopathic Personality + CP) showed the most
      robust and highest risk for future and stable CP. Also, Callous-Unemotional + CP
      children, and children who were only high in CP, often were at similar risk for
      future CP. The findings suggest that the callous-unemotional model is less
      sufficient than the multidimensional model in predicting future and stable CP.
      This can be concluded for both boys and girls and calls for more research
      reconsidering the multidimensional nature of psychopathy for CP subtyping
      purposes.

PMID- 29576676
TI  - Evolution of sex-specific pace-of-life syndromes: genetic architecture and
      physiological mechanisms.
AB  - Sex differences in life history, physiology, and behavior are nearly ubiquitous
      across taxa, owing to sex-specific selection that arises from different
      reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis
      predicts that most variation in such traits among individuals, populations, and
      species falls along a slow-fast pace-of-life continuum. As a result of their
      different reproductive roles and environment, the sexes also commonly differ in
      pace-of-life, with important consequences for the evolution of POLS. Here, we
      outline mechanisms for how males and females can evolve differences in POLS
      traits and in how such traits can covary differently despite constraints
      resulting from a shared genome. We review the current knowledge of the genetic
      basis of POLS traits and suggest candidate genes and pathways for future studies.
      Pleiotropic effects may govern many of the genetic correlations, but little is
      still known about the mechanisms involved in trade-offs between current and
      future reproduction and their integration with behavioral variation. We highlight
      the importance of metabolic and hormonal pathways in mediating sex differences in
      POLS traits; however, there is still a shortage of studies that test for sex
      specificity in molecular effects and their evolutionary causes. Considering
      whether and how sexual dimorphism evolves in POLS traits provides a more holistic
      framework to understand how behavioral variation is integrated with life
      histories and physiology, and we call for studies that focus on examining the sex
      specific genetic architecture of this integration.

PMID- 29576680
TI  - Callous-Unemotional Traits Only Versus the Multidimensional Psychopathy Construct
      as Predictors of Various Antisocial Outcomes During Early Adolescence.
AB  - The aim of this study was to compare callous-unemotional (CU) traits versus the
      multidimensional psychopathy construct in their ability to predict future and
      stable antisocial behavior. At baseline, a community sample of 996 Cypriot 12
      year old adolescents (52% girls) completed measures that tap conduct problems
      (CP) and psychopathic traits, including CU. CP, aggression, and substance use
      were self-reported at 1-3 year follow-ups. Youths were assigned to six mutually
      exclusive groups based on their baseline levels of CP and psychopathic traits.
      Youth with CP scoring high on all three psychopathic traits dimensions
      (Psychopathic Personality + CP) showed the most robust and highest risk for
      future and stable CP, aggression, and substance use, followed by youth who were
      high on all three psychopathic traits dimensions but displayed no concurrent CP
      (Psychopathic Personality Only) and CP youth with low levels of psychopathic
      traits (CP Only). Youth with CP who merely manifested callous-unemotional traits
      (Callous-Unemotional + CP) were only at risk for future CP. The findings suggest
      that the CU traits-based approach for subtyping children with CP is less
      informative compared to a subtyping approach using various psychopathic traits
      dimensions in predicting future and stable forms of various antisocial outcomes.
      These findings and their consistency with prior work indicate the need for
      additional research to examine the various psychopathic traits dimensions rather
      than focusing solely on CU traits, especially for CP subtyping purposes.

PMID- 29576681
TI  - Psychopathic Personality Works Better than CU Traits for Predicting Fearlessness
      and ADHD Symptoms among Children with Conduct Problems.
AB  - Children with early-onset conduct problems (CP) are at great risk for future
      behavior problems, and this risk seems to increase when CP co-occur with
      psychopathic traits. Even though studies are indicating that the entire
      psychopathic personality construct may be more useful in designating a meaningful
      subgroup of children with CP, research on psychopathic traits and CP in childhood
      have mainly focused on the role of callous unemotional (CU) traits. Prospective
      longitudinal data of 1867 3- to 5-year-olds (47% girls) followed annually for two
      years was used to compare groups of children with different combinations of CP
      and psychopathic traits on fearlessness and Attention-Deficit Hyperactivity
      Disorder (ADHD) symptoms. Children with CP and psychopathic personality had
      higher baseline and stable levels of ADHD symptoms than children with CP only or
      children with CP and concurrent CU traits, while baseline levels of fearlessness
      did not differ. They were also more likely to display stable levels of the risky
      combination of CP and ADHD symptoms. Results were similar for boys and girls.
      Findings indicate that there are reasons to consider other traits and behaviors
      as specifiers for subgroups of children with CP over and above CU traits, in
      order to optimize both diagnostic practice and treatment outcomes.

PMID- 29576682
TI  - Landscape metrics as predictors of hydrologic connectivity between Coastal Plain
      forested wetlands and streams.
AB  - Geographically isolated wetlands, those entirely surrounded by uplands, provide
      numerous landscape-scale ecological functions, many of which are dependent on the
      degree to which they are hydrologically connected to nearby waters. There is a
      growing need for field-validated, landscape-scale approaches for classifying
      wetlands on the basis of their expected degree of hydrologic connectivity with
      stream networks. This study quantified seasonal variability in surface hydrologic
      connectivity (SHC) patterns between forested Delmarva bay wetland complexes and
      perennial/intermittent streams at 23 sites over a full-water year (2014-2015).
      Field data were used to develop metrics to predict SHC using hypothesized
      landscape drivers of connectivity duration and timing. Connection duration was
      most strongly related to the number and area of wetlands within wetland complexes
      as well as the channel width of the temporary stream connecting the wetland
      complex to a perennial/intermittent stream. Timing of SHC onset was related to
      the topographic wetness index and drainage density within the catchment. Stepwise
      regression modelling found that landscape metrics could be used to predict SHC
      duration as a function of wetland complex catchment area, wetland area, wetland
      number, and soil available water storage (adj-R 2 = 0.74, p < .0001). Results may
      be applicable to assessments of forested depressional wetlands elsewhere in the
      U.S. Mid-Atlantic and Southeastern Coastal Plain, where climate, landscapes, and
      hydrological inputs and losses are expected to be similar to the study area.

PMID- 29576683
TI  - Vertical Distributions of Coccolithophores, PIC, POC, Biogenic Silica, and
      Chlorophyll a Throughout the Global Ocean.
AB  - Coccolithophores are a critical component of global biogeochemistry, export
      fluxes, and seawater optical properties. We derive globally significant
      relationships to estimate integrated coccolithophore and coccolith concentrations
      as well as integrated concentrations of particulate inorganic carbon (PIC) from
      their respective surface concentration. We also examine surface versus integral
      relationships for other biogeochemical variables contributed by all phytoplankton
      (e.g., chlorophyll a and particulate organic carbon) or diatoms (biogenic
      silica). Integrals are calculated using both 100 m integrals and euphotic zone
      integrals (depth of 1% surface photosynthetically available radiation). Surface
      concentrations are parameterized in either volumetric units (e.g., m-3) or values
      integrated over the top optical depth. Various relationships between surface
      concentrations and integrated values demonstrate that when surface concentrations
      are above a specific threshold, the vertical distribution of the property is
      biased to the surface layer, and when surface concentrations are below a specific
      threshold, the vertical distributions of the properties are biased to subsurface
      maxima. Results also show a highly predictable decrease in explained-variance as
      vertical distributions become more vertically heterogeneous. These relationships
      have fundamental utility for extrapolating surface ocean color remote sensing
      measurements to 100 m depth or to the base of the euphotic zone, well beyond the
      depths of detection for passive ocean color remote sensors. Greatest integrated
      concentrations of PIC, coccoliths, and coccolithophores are found when there is
      moderate stratification at the base of the euphotic zone.

PMID- 29576684
TI  - The MERRA-2 Aerosol Reanalysis, 1980 - onward, Part I: System Description and
      Data Assimilation Evaluation.
AB  - The Modern-Era Retrospective Analysis for Research and Applications, Version 2
      (MERRA-2) updates NASA's previous satellite era (1980 - onward) reanalysis system
      to include additional observations and improvements to the Goddard Earth
      Observing System, Version 5 (GEOS-5) Earth system model. As a major step towards
      a full Integrated Earth Systems Analysis (IESA), in addition to meteorological
      observations, MERRA-2 now includes assimilation of aerosol optical depth (AOD)
      from various ground- and space-based remote sensing platforms. Here, in the first
      of a pair of studies, we document the MERRA-2 aerosol assimilation, including a
      description of the prognostic model (GEOS-5 coupled to the GOCART aerosol
      module), aerosol emissions, and the quality control of ingested observations. We
      provide initial validation and evaluation of the analyzed AOD fields using
      independent observations from ground, aircraft, and shipborne instruments. We
      demonstrate the positive impact of the AOD assimilation on simulated aerosols by
      comparing MERRA-2 aerosol fields to an identical control simulation that does not
      include AOD assimilation. Having shown the AOD evaluation, we take a first look
      at aerosol-climate interactions by examining the shortwave, clear-sky aerosol
      direct radiative effect. In our companion paper, we evaluate and validate
      available MERRA-2 aerosol properties not directly impacted by the AOD
      assimilation (e.g. aerosol vertical distribution and absorption). Importantly,
      while highlighting the skill of the MERRA-2 aerosol assimilation products, both
      studies point out caveats that must be considered when using this new reanalysis
      product for future studies of aerosols and their interactions with weather and
      climate.

PMID- 29576685
TI  - Evaluation of Extratropical Cyclone Precipitation in the North Atlantic Basin: An
      analysis of ERA-Interim, WRF, and two CMIP5 models.
AB  - The representation of extratropical cyclones (ETCs) precipitation in general
      circulation models (GCMs) and a weather research and forecasting (WRF) model is
      analyzed. This work considers the link between ETC precipitation and dynamical
      strength and tests if parameterized convection affects this link for ETCs in the
      North Atlantic Basin. Lagrangian cyclone tracks of ETCs in ERA-Interim reanalysis
      (ERAI), the GISS and GFDL CMIP5 models, and WRF with two horizontal resolutions
      are utilized in a compositing analysis. The 20-km resolution WRF model generates
      stronger ETCs based on surface wind speed and cyclone precipitation. The GCMs and
      ERAI generate similar composite means and distributions for cyclone precipitation
      rates, but GCMs generate weaker cyclone surface winds than ERAI. The amount of
      cyclone precipitation generated by the convection scheme differs significantly
      across the datasets, with GISS generating the most, followed by ERAI and then
      GFDL. The models and reanalysis generate relatively more parameterized convective
      precipitation when the total cyclone-averaged precipitation is smaller. This is
      partially due to the contribution of parameterized convective precipitation
      occurring more often late in the ETC life cycle. For reanalysis and models,
      precipitation increases with both cyclone moisture and surface wind speed, and
      this is true if the contribution from the parameterized convection scheme is
      larger or not. This work shows that these different models generate similar total
      ETC precipitation despite large differences in the parameterized convection, and
      these differences do not cause unexpected behavior in ETC precipitation
      sensitivity to cyclone moisture or surface wind speed.

PMID- 29576686
TI  - How do Rumination and Social Problem Solving Intensify Depression? A Longitudinal
      Study.
AB  - In order to examine how rumination and social problem solving intensify
      depression, the present study investigated longitudinal associations among each
      dimension of rumination and social problem solving and evaluated aspects of these
      constructs that predicted subsequent depression. A three-wave longitudinal study,
      with an interval of 4 weeks between waves, was conducted. Japanese university
      students completed the Beck Depression Inventory-Second Edition, Ruminative
      Responses Scale, Social Problem-Solving Inventory-Revised Short Version, and
      Interpersonal Stress Event Scale on three occasions 4 weeks apart (n = 284 at
      Time 1, 198 at Time 2, 165 at Time 3). Linear mixed models were analyzed to test
      whether each variable predicted subsequent depression, rumination, and each
      dimension of social problem solving. Rumination and negative problem orientation
      demonstrated a mutually enhancing relationship. Because these two variables were
      not associated with interpersonal conflict during the subsequent 4 weeks,
      rumination and negative problem orientation appear to strengthen each other
      without environmental change. Rumination and impulsivity/carelessness style were
      associated with subsequent depressive symptoms, after controlling for the effect
      of initial depression. Because rumination and impulsivity/carelessness style were
      not concurrently and longitudinally associated with each other, rumination and
      impulsive/careless problem solving style appear to be independent processes that
      serve to intensify depression.

PMID- 29576687
TI  - Glyphosate dose modulates the uptake of inorganic phosphate by freshwater
      cyanobacteria.
AB  - The usefulness of glyphosate [N-(phosphonomethyl)glycine] as a source of
      nutritive phosphorus for species of halophilic cyanobacteria has been postulated
      for years. Our results indicate a stimulating effect of glyphosate on the growth
      of four out of five examined freshwater species, Anabaena variabilis (CCALA 007),
      Chroococcus minutus (CCALA 055), Fischerella cf. maior (CCALA 067) and Nostoc cf.
      muscorum (CCALA 129), in a manner dependent on the applied concentration. The
      most significant stimulation was observed at a dose of 0.1 mM glyphosate. The
      decrease in the amount of phosphonate, which correlated with microbial growth,
      demonstrated that glyphosate may play an important role in cyanobacterial
      nourishment. Surprisingly, the consumption of organic phosphorus did not start
      when concentrations of inorganic phosphate (PO43-) had fallen dramatically;
      instead, the assimilation of both types of phosphorus occurred simultaneously.
      The greatest decrease in the amount of glyphosate was observed during the first
      week. The uptake of the standard nutrient-phosphate (PO43-), was strongly
      dependent on the xenobiotic concentration. When a concentration of 0.1 mM
      glyphosate was used, the consumption of phosphate decreased in favour of
      glyphosate assimilation. Our study revealed for the very first time that the
      presence of inorganic phosphate significantly enhances the bioavailability of
      glyphosate. Statistical analysis confirmed that the nutritive usage of glyphosate
      and the absorption of phosphate are features associated with the herbicide
      concentration rather than features related to the species of freshwater
      cyanobacterium. This finding supports the thesis of an important role of organic
      phosphorus in the formation of cyanobacterial blooms and creates the opportunity
      of using these cyanobacteria to bind both organic and inorganic forms of
      phosphorus in microalgal biomasses.

PMID- 29576688
TI  - Valuable natural products from marine and freshwater macroalgae obtained from
      supercritical fluid extracts.
AB  - The biologically active compounds (fatty acids, pigments, phenolics, and
      flavonoid content) were studied in supercritical fluid extracts from the biomass
      of marine (Ulva clathrata, Cladophora glomerata, Polysiphonia fucoides, and their
      multi-species mixture) and freshwater (C. glomerata) macroalgae. Different
      extraction techniques were used in order to compare differences in the
      biologically active compound composition of the macroalgal extracts. The results
      indicated that the saturated and unsaturated fatty acids ranged from C9:0 to
      C22:0. The analysis of differences in the composition of unsaturated to saturated
      fatty acids in extracts showed that palmitic acid (C16:0) and oleic acid (C18:1,
      n-9) reached the highest value not only in marine monospecies and multi-species
      biomass but also in the freshwater macroalga C. glomerata. When comparing the
      similarity between the concentration of fatty acids and the ratio of the
      concentration of unsaturated fatty acids to saturated in macroalgal extracts, we
      found small but not statistically significant variations in values between years
      (up to 10%). This is acceptable for applications as a stable raw material for
      industrial purposes. Significantly higher values of fatty acids, carotenoids, and
      chlorophylls were obtained in the case of SC-CO2 extraction. The active
      ingredients of polyphenols, possessing antioxidant activity ranged from
      approximately 2-4%. Moreover, flavonoids represented less than 10% of the total
      content of polyphenolic compounds. The extraction efficiency of polyphenols was
      higher from a mixture of marine algae for the ultrasound-assisted extraction
      compared to freshwater. All these findings show that marine and freshwater
      macroalgae, as a raw material, have the optimal biologically active compounds
      composition for cosmetics.

PMID- 29576689
TI  - Application of feature selection methods for automated clustering analysis: a
      review on synthetic datasets.
AB  - The effective modelling of high-dimensional data with hundreds to thousands of
      features remains a challenging task in the field of machine learning. This
      process is a manually intensive task and requires skilled data scientists to
      apply exploratory data analysis techniques and statistical methods in pre
      processing datasets for meaningful analysis with machine learning methods.
      However, the massive growth of data has brought about the need for fully
      automated data analysis methods. One of the key challenges is the accurate
      selection of a set of relevant features, which can be buried in high-dimensional
      data along with irrelevant noisy features, by choosing a subset of the complete
      set of input features that predicts the output with higher accuracy comparable to
      the performance of the complete input set. Kohonen's self-organising neural
      network map has been utilised in various ways for this task, such as with the
      weighted self-organising map (WSOM) approach and this method is reviewed for its
      efficacy. The study demonstrates that the WSOM approach can result in different
      results on different runs on a given dataset due to the inappropriate use of the
      steepest descent optimisation method to minimise the weighted SOM's cost
      function. An alternative feature weighting approach based on analysis of the SOM
      after training is presented; the proposed approach allows the SOM to converge
      before analysing the input relevance, unlike the WSOM that aims to apply
      weighting to the inputs during the training which distorts the SOM's cost
      function, resulting in multiple local minimums meaning the SOM does not
      consistently converge to the same state. We demonstrate the superiority of the
      proposed method over the WSOM and a standard SOM in feature selection with
      improved clustering analysis.

PMID- 29576690
TI  - Deep imitation learning for 3D navigation tasks.
AB  - Deep learning techniques have shown success in learning from raw high-dimensional
      data in various applications. While deep reinforcement learning is recently
      gaining popularity as a method to train intelligent agents, utilizing deep
      learning in imitation learning has been scarcely explored. Imitation learning can
      be an efficient method to teach intelligent agents by providing a set of
      demonstrations to learn from. However, generalizing to situations that are not
      represented in the demonstrations can be challenging, especially in 3D
      environments. In this paper, we propose a deep imitation learning method to learn
      navigation tasks from demonstrations in a 3D environment. The supervised policy
      is refined using active learning in order to generalize to unseen situations.
      This approach is compared to two popular deep reinforcement learning techniques:
      deep-Q-networks and Asynchronous actor-critic (A3C). The proposed method as well
      as the reinforcement learning methods employ deep convolutional neural networks
      and learn directly from raw visual input. Methods for combining learning from
      demonstrations and experience are also investigated. This combination aims to
      join the generalization ability of learning by experience with the efficiency of
      learning by imitation. The proposed methods are evaluated on 4 navigation tasks
      in a 3D simulated environment. Navigation tasks are a typical problem that is
      relevant to many real applications. They pose the challenge of requiring
      demonstrations of long trajectories to reach the target and only providing
      delayed rewards (usually terminal) to the agent. The experiments show that the
      proposed method can successfully learn navigation tasks from raw visual input
      while learning from experience methods fail to learn an effective policy.
      Moreover, it is shown that active learning can significantly improve the
      performance of the initially learned policy using a small number of active
      samples.

PMID- 29576691
TI  - Structural reliability calculation method based on the dual neural network and
      direct integration method.
AB  - Structural reliability analysis under uncertainty is paid wide attention by
      engineers and scholars due to reflecting the structural characteristics and the
      bearing actual situation. The direct integration method, started from the
      definition of reliability theory, is easy to be understood, but there are still
      mathematics difficulties in the calculation of multiple integrals. Therefore, a
      dual neural network method is proposed for calculating multiple integrals in this
      paper. Dual neural network consists of two neural networks. The neural network A
      is used to learn the integrand function, and the neural network B is used to
      simulate the original function. According to the derivative relationships between
      the network output and the network input, the neural network B is derived from
      the neural network A. On this basis, the performance function of normalization is
      employed in the proposed method to overcome the difficulty of multiple
      integrations and to improve the accuracy for reliability calculations. The
      comparisons between the proposed method and Monte Carlo simulation method,
      Hasofer-Lind method, the mean value first-order second moment method have
      demonstrated that the proposed method is an efficient and accurate reliability
      method for structural reliability problems.

PMID- 29576692
TI  - Pharmacognosy Magazine's Performance in the Year 2017: A Report.

PMID- 29576693
TI  - Sulforaphane salads.

PMID- 29576694
TI  - Hypolipidemic Effect of Psidium guajava Leaf Extract Against Hepatotoxicity in
      Rats.
AB  - Background: Plant-based natural extracts cure several diseases in human. However,
      the extract of Psidium guajava leaf is not yet evaluated on changes of lipid
      profile in hepatic disease affected rats. Objective: The present study was aimed
      to evaluate the mitigation effect of the ethanolic extract of P. guajava leaf and
      its isolated quercetin fraction on hepatotoxic rats. Materials and Methods:
      Carbon tetrachloride (CCl4) was injected to rats for hepatic disease induction
      and silymarin drug was used as positive control to compare plant ethanolic
      extract. The lipid profiles were assessed in both plasma and liver tissue of
      diseased and control rats. Results: Levels of total cholesterol, triglycerides,
      free fatty acids, phospholipids, and low-density lipoprotein cholesterol were
      increased and the level of high-density lipoprotein cholesterol (HDL-C) was
      decreased in CCl4-induced hepatotoxic rats. The treatment of P. guajava (100,
      200, and 300 mg/kg, bw) and isolated quercetin fraction (20 mg/kg, bw) doses
      decreased the elevated levels of all these parameters in diseased rats and
      restored the normal concentration of HDL-C. Conclusion: The results of the
      present study concluded that the P. guajava leaf and its isolated quercetin
      fraction can significantly regulate lipid metabolism in CCl4-induced hepatotoxic
      rats and decrease the disease rate. SUMMARY: Psidium guajava leaf extract reduces
      the hepatotoxicity and disease rate in ratsQuercetin fraction of leaf extract
      significantly regulates lipid profile in hepatic diseased rats. Abbreviations
      used: CCl4: Carbon tetrachloride; FFA: Free fatty acids; HDL-C: High-density
      lipoprotein cholesterol; LCAT: Lecithin cholesterol acyltransferase; LDL-C: Low
      density lipoprotein cholesterol; PL: Phospholipids; TC: Total cholesterol; TG:
      Triglycerides; VLDL-C: Very low-density lipoprotein cholesterol.

PMID- 29576695
TI  - Demethoxycurcumin, a Natural Derivative of Curcumin Abrogates Rotenone-induced
      Dopamine Depletion and Motor Deficits by Its Antioxidative and Anti-inflammatory
      Properties in Parkinsonian Rats.
AB  - Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      (NDD) associated with the loss of dopaminergic neurons in the substantia nigra
      and subsequently has an effect on motor function and coordination. The pathology
      of PD is multifactorial, in which neuroinflammation and oxidative damage are the
      two of the main protagonists. Objectives: The present study aims to assess the
      potential antioxidant and anti-inflammatory effects of demethoxycurcumin (DMC), a
      natural derivative of curcumin, against rotenone-induced PD in rats. Materials
      and Methods: Rats were randomized and divided into six groups: control, rotenone
      (0.5 mg/kg/day, intraperitoneal in sunflower oil) treated for 7 days, rotenone
      and DMC (5, 10, and 20 mg/kg b.w) cotreated, and DMC (20 mg/kg b.w) alone treated
      groups. Results: Based on the dopamine concentration and biochemical estimations,
      the effective dose of DMC was selected and the chronic study was performed. At
      the end of the experimental period, behavioral studies and protein expression
      patterns of inflammatory markers were analyzed. Rotenone treatment led to motor
      dysfunctions, neurochemical deficits, and oxidative stress and enhanced
      expressions of inflammatory markers, whereas oral administration of DMC
      attenuated all the above. Conclusion: Even though further research is needed to
      prove its efficacy in clinical trial, the results of our study showed that DMC
      may offer a promising and new therapeutic lead for the treatment of NDDs
      including PD. SUMMARY: Curcumin and their derivatives have been shown to be
      potent neuroprotective effectDemethoxycurcumin (DMC) amolerated the rotenone
      induced behavioural alterationsDMC abrogated the rotenone induced dopamine
      deficitsDMC attenuated the rotenone induced oxidative stressDMC diminished the
      rotenone mediated inflammation. Abbreviations used: COX-2: Cyclooxygenase-2; DA:
      Dopamine; DMC: Demethoxycurcumin; DMRT: Duncan's multiple range test; GSH:
      Reduced glutathione; GPx: Glutathione peroxidase; IL-1 beta: Interleukin-1 beta;
      IL-6: Interleukin-6; iNOS: Inducible nitric oxide synthase; PD: Parkinson's
      disease; SN: Substantia nigra; SOD: Superoxide dismutase; TBARS: Thiobarbituric
      acid reactive substances; TNF-alpha: Tumor necrosis factor-alpha.

PMID- 29576696
TI  - Optimization for Decocting Later of Menthae Herba in Eungyo-San, a Herbal
      Formula, Using Response Surface Methodology with Gas Chromatography/Mass
      Spectrometry.
AB  - Background: "Decocting later" is important procedure for the extraction of herbal
      medicines containing volatile compounds. Objective: This study was performed to
      investigate optimal conditions for "Decocting later" of Menthae herba in Eungyo
      san (EGS) and correlation between extraction variables and the yields of d/l
      menthol, a marker compound of Menthae herba. Materials and Methods: The decocting
      temperature, total decocting time, and decocting later time were chosen as
      individual variables, and the yield of d/l-menthol was set as the response value
      which were calculated by using a Box-Behnken design (BBD). The amount of d/l
      menthol was quantified using gas chromatography/mass spectrometry. Results:
      Response surface methodology (RSM) was used to predict optimal conditions for
      decocting later of Menthae herba into the formula. Optimal conditions for
      "Decocting later" from RSM were as follows: 100.63 degrees C of decocting
      temperature; 82.95 min of total decocting time; 19.11 min of decocting later
      time. Both decocting temperature and total decocting time showed significant
      correlation with the yield of d/l-menthol. Conclusions: These results suggest
      that the decocting temperature and total decocting time were influential factors,
      and RSM can be applied for optimizing the conditions of "Decocting later" of
      Menthae herba in EGS. SUMMARY: Gas chromatography/mass spectrometry method
      developed was applied to quantify the d/l-menthol, a volatile compound in Menthae
      Herba, in Eungyo-san decoction (EGS)d/l-Menthol was extracted in the chloroform
      layer of the partition between EGS decoction and chloroformA Box-Behnken design
      produced the predicted response values (yield of d/l-menthol in EGS) from the
      actual response values with individual variables including decocting temperature,
      total decocting time, and decocting later timeOptimal conditions for "Decocting
      later" of Menthae Herba in EGS obtained from the response surface methodology
      were 100.63 degrees C of decocting temperature, 82.95 min of total decocting
      time, and 19.11 min of decocting later time. Abbreviations used: KM: Korean
      medicine; EGS: Eungyo-san; GC/MS: Gas chromatography/mass spectrometry; RSM:
      Response surface methodology; SIM: Selected ion monitoring; LOD: Limits of
      determination; LOQ: Limits of quantification; RSD: Relative standard deviation;
      ANOVA: Analysis of variance; BBD: Box-Behnken design.

PMID- 29576697
TI  - Optimization of Microwave-assisted Extraction of Silymarin from Silybum marianum
      Straws by Response Surface Methodology and Quantification by High-Performance
      Liquid Chromatograph Method.
AB  - Background: Silybum marianum, a member of the Aster family, is a well-known
      Chinese herb and the source of a popular antioxidant that is extensively used in
      Asia. The abundant S. marianum straws are still underutilized and wastefully
      discarded to pollute the environment. Objective: To solve the above problem and
      better utilize S. marianum straws, the objective of this study was to optimize
      the conditions for extraction of silymarin from S. marianum straws. Materials and
      Methods: A combination of microwave-assisted extraction and response surface
      methodology (RSM) was used for silymarin from S. marianum straws and yield
      assessment by high-performance liquid chromatography method. The RSM was based on
      a five-level, four-variable central composite design (CCD). Results: The results
      indicated that the optimal conditions to obtain highest yields of silymarin were
      microwave power of 146 W, extraction time of 117 s, liquid-to-solid ratio of 16:1
      mL/g, and ethanol concentration of 43% (v/v). Validation tests indicated that
      under the optimized conditions, the actual yield of silymarin was 6.83 +/- 0.57
      mg/g with relative standard deviation of 0.92% (n = 5), which was in good
      agreement with the predicted yield. Conclusions: The exploitation of the natural
      plant resources present very important impact for the economic development. The
      knowledge obtained from this work should be useful to further exploit and apply
      this material. SUMMARY: Silymarin has been isolated from Silybum marianum straws
      by microwave-assisted extraction and response surface methodologyThe results
      obtained are helpful for the full utilization of S. marianum strawsThe microwave
      assisted extraction is a very useful method for the extraction of important
      phytochemicals from plant materials. Abbreviations used: MAE: Microwave-assisted
      extraction, RSM: Response surface methodology, HPLC: High-performance liquid
      chromatography, CCD: Central composite design, ANOVA: Analysis of variance.

PMID- 29576698
TI  - Ameliorative Effect of Camel's Milk and Nigella Sativa Oil against Thioacetamide
      induced Hepatorenal Damage in Rats.
AB  - Background: Camel milk (CM) and Nigella sativa (NS) have been traditionally
      claimed to cure wide range of diseases and used as medicine in different part of
      world, particularly in Saudi Arabia. Several research studies have been published
      that proved beneficial effects of CM and NS. Objective: This study was undertaken
      to investigate the antihepatotxic potential of CM and NS oil (NSO) against
      thioacetamide (TAA)-induced hepato and nephrotoxicity in rats. Materials and
      Methods: Thirty female Albino Wistar rats were randomly divided in to six groups
      having five rats in each group. A single subcutaneous injection of TAA (100 mg/kg
      b. w.) was administered to all the rats in Group-II to VI on 1st day to induce
      hepatorenal damage. Group I served as a normal control while Group II served as
      toxic control for comparison purpose. Experimental animals in Group III, IV, and
      V were supplemented with fresh CM, (250 mL/24 h/cage), NSO (2 mL/kg/day p. o.),
      and NSO + fresh CM, respectively. Group VI was treated with a polyherbal
      hepatoprotective Unani medicine Jigreen (2 mL/kg/day p. o.) for 21 days. TAA
      induced hepatorenal damage and protective effects of CM and NSO were assessed by
      analyzing liver and kidney function tests in the serum. Histopathology of liver
      and kidney tissues was also carried out to corroborate the findings of
      biochemical investigation. Results: The results indicated that the TAA
      intoxicated rats showed significant increase in the alanine transaminase,
      aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase,
      lipid profile, urea, creatinine, uric acid, sodium, and potassium levels in
      serum. Treatment of rats with CM, NSO, and CM plus NSO combination and Jigreen
      significantly reversed the damage and brought down the serum biochemical
      parameters and lipid profile toward the normal levels. The histopathological
      studies also support the hepato and nephroprotective effects of CM and NSO.
      Conclusion: This study demonstrated the ameliorative effects of CM, NSO, and CM
      plus NSO combination against TAA-induced hepatorenal toxicity in rats. SUMMARY:
      The antihepatotxic potential of Camel's Milk (CM) and Nigella sativa oil (NSO)
      against thioacetamide (TAA) induced hepatorenal toxicity was evaluated in ratsThe
      oral administration of fresh CM (250 mL/24h/cage), NSO (2 mL/kg/day) and
      NSO+fresh CM and Jigreen (2 mL/kg/day) for 21 days significantly decreased the
      hepatorenal toxicity as evidenced from analyzed biochemical parameters in serum
      and histopathological studies of liver and kidney tissuesThis study demonstrated
      the ameliorative effects of CM and NSO against TAA induced hepatorenal toxicity.
      Abbreviations used: CM: Camel milk; NS: Nigella sativa; NSO: Nigella sativa Oil;
      TAA: Thioacetamide; S.C.: Subcutaneous; Jig: Jigreen; b.w.: Body Weight; mL:
      Milli liter; mg: Milli gram; g: Gram; Kg: Kilo gram; ALT: Alanine transaminase;
      AST: Aspartate transaminase; GGT: Gamma-Glutamyl Transpeptidase; ALP: Alkaline
      Phosphatase; TC: Total Cholesterol; HDL-C: High Density Lipoprotein Cholesterol;
      LDL-C: Low Density Lipoprotein Cholesterol; TG: Triglyceride; TB: Total
      bilirubin; K+: Potassium; Na+: Sodium; CCl4: Carbon Tetrachloride;  degrees C:
      Degree Celsius; p.o.: Per Oral; RPM: Revolutions per minute; H&E: Hematoxylin and
      Eosin; SEM: Standard Error of Mean; ANOVA: The one-way analysis of variance.

PMID- 29576699
TI  - Modeling and Optimum Extraction of Multiple Bioactive Exopolysaccharide from an
      Endophytic Fungus of Crocus sativus L.
AB  - Background: Crocus sativus L. (saffron) is a scarce plant that has been used as
      food flavoring agent, coloring agent, and traditional herbal medicine. Methods:
      The bioactivity of exopolysaccharide (EPS) extracted from an endophytic fungus of
      C. sativus was examined for the first time by antioxidative, antitumor, and
      antibacterial assays. The extraction conditions for EPS were optimized by
      combining the response surface methodology with Box-Behnken design. Results: EPS
      exhibited excellent scavenging activities against 1,1-diphenyl-2-picrylhydrazyl,
      hydroxyl and superoxide anion radicals, and moderate cytotoxicities against K562,
      A549, HL-60, and HeLa cells. The optimum extraction conditions for EPS were as
      follows: precipitation time of 16 h, precipitation temperature of 3.7 degrees C,
      pH 7.2, and ratio of ethanol to fermented broth of 5:1 (L/L). Under the optimized
      conditions, the yield of EPS reached 162 +/- 6 MUg/L which was close to the
      predicted one (165 MUg/L). Moreover, high-performance liquid chromatography of
      monosaccharide composition showed that EPS comprised mannose, glucose, galactose
      xylose, and arabinose in a molar ratio of 25.6:16.5:1.0:3.8:5.4. Conclusion: EPS
      may be an eligible substitute for C. sativus and a potential bioactive source
      applicable to pharmaceutical and food industries. SUMMARY: Exopolysaccharide
      (EPS) from endophytic fungus of Crocus sativus was studied for the first timeEPS
      extraction was optimized by combining response surface methodology with Box
      Behnken designMonosaccharide composition and EPS structure were identified by
      high-performance liquid chromatography and Fourier-transform infrared
      spectroscopy. Abbreviations used: EPS: Exopolysaccharide, RSM: Response surface
      methodology, BBD: Box-Behnken design, DPPH: 1,1-diphenyl-2-picrylhydrazyl, VC:
      Ascorbic acid, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,
      LB: Luria Bertani, DMSO: dimethyl sulfoxide, PMP: 1-phenyl-3-methyl-5-pyrazolone,
      FT-IR: Fourier transform-infrared, HPLC: High-performance liquid chromatography,
      3D: Three-dimensional, 2D: Two-Dimensional.

PMID- 29576700
TI  - Combined Antihypertensive Effect of Paeoniflorin Enriched Extract and Metoprolol
      in Spontaneously Hypertensive Rats.
AB  - Background: Hypertension is a great global health challenge and it mostly
      requires drug combination therapy with the various advantages. Metoprolol (MP)
      and paeoniflorin are both commonly used for the treatment of hypertension.
      However, whether they exert synergistic effects on antihypertension or not
      remains unclear, especially on vascular endothelial function. Objective: The
      purpose of the study is to investigate the advantages of the combined
      antihypertensive effects of paeoniflorin enriched extract from Radix Paeoniae
      Alba (RE) and MP in spontaneously hypertensive rats (SHR). Materials and Methods:
      SHR divided into six groups (n = 8 each group), animals in each group were
      administrated orally with distilled water, MP (6 and 20 mg/kg), RE (30 and 90
      mg/kg), and MP (6 mg/kg) combined with RE (30 mg/kg) (MP + RE), respectively,
      daily for 6 weeks. Blood pressure (BP) and microcirculation were assessed. The
      organ bath experiment and hematoxylin and eosin staining were, respectively,
      performed for the functional and pathological vascular function analysis.
      Immunohistochemistry was applied to detect endothelial nitric oxide synthase
      (eNOS) expression in aorta, heart, and kidney. Further, high-performance liquid
      chromatography was employed to quantitatively determine paeoniflorin in RE and MP
      + RE sample solvent, as well as in plasma of Sprague-Dawley rats (SD) after
      single-dose administration of them. Results: The results showed that MP + RE
      significantly reduced BP, increased microcirculation, improved vascular function
      and pathological changes, and upregulated eNOS expression. MP was also found to
      increase the blood concentration of paeoniflorin in SD. Conclusion: The
      combination of RE and MP could be used for the treatment of hypertension and
      could improve microcirculation, upregulate eNOS expression, and mitigate
      endothelial dysfunction in SHR. SUMMARY: Paeoniflorin enriched extract from Radix
      Paeoniae Alba and metoprolol exert synergistic antihypertensive effects.
      Abbreviations used: RE: Paeoniflorin enriched extract from Radix Paeoniae Alba,
      MP: Metoprolol, MP + RE: MP combined with RE, NC: Normal control, MC: Model
      control, SHR: Spontaneously hypertensive rats, SD: Sprague-Dawley rats, H and E:
      Hematoxylin and eosin, BP: Blood pressure, SBP: Systolic blood pressure, DBP:
      Diastolic blood pressure, MBP: Mean arterial blood pressure, NA: Norepinephrine,
      ACh: Acetylcholine, SNP: Nitroprusside, NO: Nitric oxide, eNOS: Endothelial
      nitric oxide synthase, RPA: Radices Paeoniae Alba, IHC: Immunohistochemistry,
      Cmax: Peak concentration, Tmax: The time to reach Cmax, t1/2: Half-life, AUC0-t:
      Area under the curve of 0-t time; MRT0-t: Mean residence of 0-t time; CL:
      Clearance rate.

PMID- 29576701
TI  - Evaluation of Antioxidant, Antimicrobial, and Antiurolithiatic Potential of
      Different Solvent Extracts of Aerva lanata Linn Flowers.
AB  - Introduction: Aerva lanata (Linn) of family Amaranthaceae is an important and
      commonly used plant for its medicinal and pharmacological properties and proving
      the traditional uses of flowers of A. lanata Linn. Objective: All extracts of A.
      lanata were further evaluated for antioxidant, antimicrobial, and
      antiurolithiatic potential to scientifically prove the traditional uses.
      Materials and Methods: In the present investigation, different solvent extracts
      of flowers were obtained using a Soxhlet extractor. Microorganisms were obtained
      from IMTECH, Chandigarh. Antiurolithiatic study was carried out in Albino
      Research and Training Centre, Hyderabad. Results: Regardless of the antioxidant
      studied, the methanolic extract presented the highest antioxidant activity and
      the aqueous extracts offered the lowest, following the order: methanolic extract
      > ethyl acetate > chloroform > aqueous. The results of this antimicrobial study
      indicate that methanolic extract of A. lanata could be used as antimicrobial
      agents. Overall, the methanolic flower extract of A. lanata (Linn) was
      significantly more promising as antiurolithiatic spectrum. This result also
      suggested the potential usefulness of the methanolic extract as an
      antiurolithiatic agent. Conclusion: Henceforward, this research can be
      acknowledged as a prime new report that focuses on the application of A. lanata
      (Linn) as an antioxidant, antimicrobial, and antiurolithiatic agent. SUMMARY:
      Overall, methanolic flower extract of Aerva lanata Linn showed promising
      antioxidant activityAdditionally, methanolic flower extract of A. lanata Linn
      exhibited remarkable antimicrobial and antiurolithiatic potential. Abbreviations
      used: IMTECH Chandigarh: Institute of Microbial Technology, Chandigarh; IMMT:
      Institute of Mineral and Material Technology; CSIR: Council of Scientific &
      Industrial Research; DPPH: 1,1-diphenyl-2-picrylhydrazyl; MTCC: Microbial Type
      Culture Collection; BHT: Butylated Hydroxyl Toluene.

PMID- 29576702
TI  - The Standardized Extract of Limonium tetragonum Alleviates Chronic Alcoholic
      Liver Injury in C57Bl/6J Mice.
AB  - Background: In traditional folk medicine, Limonium tetragonum is used in the
      treatment of uterine hemorrhage, tinnitus, and oligomenorrhea. Objective: This
      study aimed to identify the therapeutic effect of L. tetragonum EtOAc extract
      (EALT) on liver of mice with chronic alcohol poisoning. Materials and Methods:
      C57BL/6J mice were administered 100 mg/kg of EALT with a single binge
      ethanol/Lieber-DeCarli liquid diet for 8 weeks. Results: The chronic-binge
      ethanol diet induced a significant increase in liver marker enzyme activities.
      Coadministration of EALT reversed the elevation of serum total cholesterol and
      triglyceride as well as aspartate aminotransferase and alanine aminotransferase
      due to chronic alcohol consumption. Histologic findings including markedly
      attenuated fat accumulation in hepatocytes were observed in EALT-treated mice.
      EALT supplementation prevented alcoholic liver injury through attenuation of
      inflammatory mediators such as toll-like receptor-4, cytochrome P4502E1, and
      cyclooxygenase-2, and inflammatory cytokine interleukin-6. Conclusion: Results
      provided direct experimental evidence for the hepatoprotective effect of EALT in
      the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might
      be useful in the management of alcoholic liver disease. SUMMARY: Halophyte
      Limonium tetragonum has recently been of interest in Korea for its nutritional
      value and salty taste which made it an ideal vegetablePhytochemical analysis of
      L. tetragonum EtOAc extract (EALT) resulted in nine compounds including catechins
      and myricetin glycosides as main componentsAdministration of EALT for 8 weeks
      showed hepatoprotective effect on Lieber-DeCarli diet-fed mouse modelA
      significant decrease in liver marker enzymes and inflammatory mediators was also
      detected. Abbreviations used: EALT: L. tetragonum EtOAc extract; TC: Total
      cholesterol; TG: Triglyceride; ROS: Reactive oxygen species; CYP2E1: Cytochrome
      P4502E1; TLR-4: Toll-like receptor-4; COX-2: Cyclooxygenase-2.

PMID- 29576703
TI  - Identification of Three Kinds of Citri Reticulatae Pericarpium Based on
      Deoxyribonucleic Acid Barcoding and High-performance Liquid Chromatography-diode
      Array Detection-electrospray Ionization/Mass Spectrometry/Mass Spectrometry
      Combined with Chemometric Analysis.
AB  - Background: Citri Reticulatae Pericarpium is the dried mature pericarp of Citrus
      reticulata Blanco which can be divided into "Chenpi" and "Guangchenpi."
      "Guangchenpi" is the genuine Chinese medicinal material in Xinhui, Guangdong
      province; based on the greatest quality and least amount, it is most expensive
      among others. Hesperidin is used as the marker to identify Citri Reticulatae
      Pericarpium described in the Chinese Pharmacopoeia 2010. However, both "Chenpi"
      and "Guangchenpi" contain hesperidin so that it is impossible to differentiate
      them by measuring hesperidin. Objective: Our study aims to develop an efficient
      and accurate method to separate and identify "Guangchenpi" from other Citri
      Reticulatae Pericarpium. Materials and Methods: The genomic deoxyribonucleic acid
      (DNA) of all the materials was extracted and then the internal transcribed spacer
      2 was amplified, sequenced, aligned, and analyzed. The secondary structures were
      created in terms of the database and website established by Jorg Schultz et al.
      High-performance liquid chromatography-diode array detection-electrospray
      Ionization/mass spectrometry (HPLC-DAD-ESI-MS)/MS coupled with chemometric
      analysis was applied to compare the differences in chemical profiles of the three
      kinds of Citri Reticulatae Pericarpium. Results: A total of 22 samples were
      classified into three groups. The results of DNA barcoding were in accordance
      with principal component analysis and hierarchical cluster analysis. Eight
      compounds were deduced from HPLC-DAD-ESI-MS/MS. Conclusions: This method is a
      reliable and effective tool to differentiate the three Citri Reticulatae
      Pericarpium. SUMMARY: The internal transcribed spacer 2 regions and the secondary
      structure among three kinds of Citri Reticulatae Pericarpium varied
      considerablyAll the 22 samples were analyzed by high-performance liquid
      chromatography (HPLC) to obtain the chemical profilesPrincipal component analysis
      and hierarchical cluster analysis were used in the chemometric
      analysisdeoxyribonucleic acid barcoding and HPLC-diode array detection
      electrospray ionization/mass spectrometry/MS coupled with chemometric analysis
      provided an accurate and strong proof to identify these three herbs.
      Abbreviations used: CTAB: Hexadecyltrimethylammonium bromide, DNA:
      Deoxyribonucleic acid, ITS2: Internal transcribed spacer 2, PCR: Polymerase chain
      reaction.

PMID- 29576704
TI  - Quantitative Determination of Bioactive Constituents in Noni Juice by High
      performance Liquid Chromatography with Electrospray Ionization Triple Quadrupole
      Mass Spectrometry.
AB  - Background: Noni juice has been extensively used as folk medicine for the
      treatment of arthritis, infections, analgesic, colds, cancers, and diabetes by
      Polynesians for many years. Due to the lack of standard scientific evaluation
      methods, various kinds of commercial Noni juice with different quality and price
      were available on the market. Objective: To establish a sensitive, reliable, and
      accurate high-performance liquid chromatography with electrospray ionization
      triple quadrupole mass spectrometry (HPLC-ESI-MS/MS) method for separation,
      identification, and simultaneous quantitative analysis of bioactive constituents
      in Noni juice. Materials and Methods: The analytes and eight batches of
      commercially available samples from different origins were separated and analyzed
      by the HPLC-ESI-MS/MS method on an Agilent ZORBAX SB-C18 (150 mm * 4.6 mm i.d., 5
      MUm) column using a gradient elution of acetonitrile-methanol-0.05% glacial
      acetic acid in water (v/v) at a constant flow rate of 0.5 mL/min. Results: Seven
      components were identification and all of the assay parameters were within the
      required limits. Components were within the correlation coefficient values (R2 >=
      0.9993) at the concentration ranges tested. The precision of the assay method was
      <0.91% and the repeatability between 1.36% and 3.31%. The accuracy varied from
      96.40% to 103.02% and the relative standard deviations of stability were <3.91%.
      Samples from the same origin showed similar content while different origins
      showed significant different result. Conclusions: The developed methods would
      provide a reliable basis and be useful in the establishment of a rational quality
      control standard of Noni juice. SUMMARY: Separation, identification, and
      simultaneous quantitative analysis method of seven bioactive constituents in Noni
      juice is originally developed by high-performance liquid chromatography with
      electrospray ionization triple quadrupole mass spectrometryThe presented method
      was successfully applied to the quality control of eight batches of commercially
      available samples of Noni juiceThis method is simple, sensitive, reliable,
      accurate, and efficient method with strong specificity, good precision, and high
      recovery rate and provides a reliable basis for quality control of Noni juice.
      Abbreviations used: HPLC-ESI-MS/MS: High-performance liquid chromatography with
      electrospray ionization triple quadrupole mass spectrometry, LOD: Limit of
      detection, LOQ: Limit of quantitation, S/N: Signal-to-noise ratio, RSD: Relative
      standard deviations, DP: Declustering potential, CE: Collision energy, MRM:
      Multiple reaction monitoring, RT: Retention time.

PMID- 29576705
TI  - Antibacterial Activity of Azadirachta indica, Pongamia pinnata, Psidium guajava,
      and Mangifera indica and their mechanism of action against Streptococcus mutans.
AB  - Background: Curative plants have reportedly been used to make chewing
      sticks/toothbrushes intended for the treatment of oral diseases. Objective: The
      in vitro antibacterial activities of Azadirachta indica, Pongamia pinnata,
      Psidium guajava, and Mangifera indica were evaluated against Streptococcus
      mutans, along with the cytotoxicity and antioxidant and synergistic potentials.
      The effect of M. indica on the expression of crucial virulence genes spaP and
      gtfB of S. mutans was determined. Materials and Methods: The antibacterial
      activity was determined using a modified microdilution method. The antioxidant
      potential was evaluated using diphenyl picrylhydrazyl (DPPH), Griess reagent, and
      nitroblue tetrazolium calorimetric assays. The synergistic activity was
      investigated using a modified checkerboard method, while the cytotoxicity was
      determined according to a cell proliferation 2,3-Bis-(2-methoxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Reverse transcription was
      the chosen method for determining the difference in expression of the spaP and
      gtfB genes after treatment with the plant sample. Results: M. indica and A.
      indica had the highest antibacterial activity at concentrations of 0.3 mg/ml and
      6.25 mg/ml, respectively. A. indica had the best free radical scavenging of DPPH,
      exhibiting 50% inhibition at 28.72 MUg/ml; while M. indica showed better
      superoxide scavenging potential than the positive control quercetin. Both M.
      indica and A. indica had adequate activity against the nitric oxide-free radical
      (12.87 and 18.89 MUg/ml, respectively). M. indica selectively reduced the
      expression of the gtfB gene, indicating a mechanism involving Glucotranferases,
      specifically targeting bacterial attachment. SUMMARY: Mangifera indica and
      Azadirachta indica had very good antibacterial activity against Streptococcus
      mutans and moderate toxicity against Vero cellsM. indica had the best antioxidant
      capacity overallM. indica reduced the expression of gtfB gene at 0.5 mg/ml.
      Abbreviations used: AA: Ascorbic acid; BHI: Brain-heart infusion; CHX:
      Chlorhexidine; DPPH: Diphenyl picrylhydrazyl; DMSO: Dimethlysulfoxide; NBT:
      Nitroblue tetrazolium; NO: Nitric oxide.

PMID- 29576706
TI  - Rhynchophylline Downregulates Phosphorylated cAMP Response Element Binding
      Protein, Nuclear Receptor-related-1, and Brain-derived Neurotrophic Factor
      Expression in the Hippocampus of Ketamine-induced Conditioned Place Preference
      Rats.
AB  - Background: Addiction to ketamine is becoming a serious public health issues, for
      which there exists no effective treatment. Rhynchophylline (Rhy) is an alkaloid
      extracted from certain Uncaria species that is well known for both its potent
      anti-addictive and neuroprotective properties. Increasing evidence supports the
      contributions of cAMP response element binding protein (CREB), nuclear receptor
      related-1 (Nurr1), and brain-derived neurotrophic factor (BDNF) in modulating
      neural and behavioral plasticity which was induced by addictive drugs. Objective:
      To investigate the effects of Rhy on the behavior and the levels of
      phosphorylated CREB (p-CREB), Nurr1, and BDNF in the hippocampus of ketamine
      induced conditioned place preference (CPP) rats. Materials and Methods: CPP
      paradigm was used to establish the model of ketamine-dependent rats and to
      evaluate the effect of Rhy on ketamine dependence. The expressions of p-CREB,
      Nurr1, and BDNF were tested by Western blotting and immunohistochemistry.
      Results: We observed that Rhy can reverse the behavior preference induced by
      ketamine CPP training. At the same time, expression of p-CREB, Nurr1, and BDNF,
      which was significantly increased by ketamine, was restored in the Rhy -treated
      group. Conclusion: This study indicates that Rhy can reverse the reward effect
      induced by ketamine in rats and the mechanism can probably be related to regulate
      the hippocampal protein expression of p-CREB, Nurr1, and BDNF. SUMMARY: P-CREB,
      Nurr1 and BDNF play an important role in the formation of ketamine-induced place
      preference in ratsRhynchophylline reversed the expression of p-CREB, Nurr1 and
      BDNF which was activated by ketamine in the hippocampusRhynchophylline
      demonstrates the potential effect of mediates ketamine induced rewarding effect.
      Abbreviations used: Rhy: Rhynchophylline; CREB: cAMP response element binding
      protein; Nurr1: Nuclear receptor-related-1; BDNF: Brain-derived neurotrophic
      factor; CPP: Conditioned place preference; NMDA: N-methyl-D-aspartic acid; METH:
      Methamphetamine; CNS: Central nervous system; PFA: Paraformaldehyde; GAPDH:
      Glyceraldehyde-3-phosphate dehydrogenase; LTP: long-term potentiation.

PMID- 29576708
TI  - Further Study of Influence of Panax notoginseng on Intestinal Absorption
      Characteristics of Triptolide and Tripterine in Rats with Tripterygium wilfordii.
AB  - Background: Tripterygium wilfordii (TW) is widely employed to treat rheumatoid
      arthritis and autoimmune disorders clinically, which, however, accompany with
      disturbing hepatotoxicity and nephrotoxicity. The previous research showed that
      Panax notoginseng (PN) compatibly and significantly reduces the TW-induced
      hepatotoxicity. Objective: To explore the underlying mechanism, the present study
      was designed to reveal the influence of PN on the intestinal absorption process
      of TW-derived active components in rat. Materials and Methods: An in situ single
      pass intestinal perfusion technique was established and preformed to obtain the
      perfusate samples of triptolide (TP), tripterine (TE), TW extract, and TW-PN
      extract. A rapid and sensitive ultra-performance liquid-chromatography tandem
      mass spectrometry method was subsequently developed and validated to determine
      the concentrations of TP and TE in the perfusate samples. Then, the absorption
      parameters, effective permeability, absorption rate constant, and percentage of
      10 cm intestinal absorption were calculated strictly. Results: The final data
      indicated that both TP and TE have no special absorption site in the intestine
      and are primarily absorbed in a passive manner. Otherwise, the absorption of TP
      was decreased from compatibility of PN, but the absorption of TE was enhanced.
      Conclusion: The absorption reduction of TP and absorption elevation of TE from TW
      initiated by the combination of PN are contributed to attenuate the toxicity and
      reinforce the therapeutic efficacy of TW. It is practically reasonable of usage
      of TW compatibility with PN clinically. SUMMARY: Panax notoginseng (PN) regulated
      the absorption process of Tripterygium wilfordii (TW) in intestineBoth triptolide
      (TP) and tripterine (TE), two typical components of TW, have no special
      absorption site in the intestine and are primarily absorbed in a passive mannerPN
      decreased the absorption of TP and enhanced the absorption of TE in the
      intestine. Abbreviations used: 10 cm% ABS: percentage of 10 cm intestinal
      absorption, DMARDs: Disease-modifying antirheumatic drugs, GU: Glycyrrhiza
      uralensis, Ka: Absorption rate constant, NSAIDs: Nonsteroidal anti-inflammatory
      drugs, Peff: Effective permeability, PN: Panax notoginseng, QC: Quality control,
      RA: Rheumatoid arthritis, RG: Rehmannia glutinosa, SPIP: Single-pass intestinal
      perfusion, TE: Tripterine, TP: Triptolide, TW: Tripterygium wilfordii, UPLC
      MS/MS: Ultra-performance liquid-chromatography tandem mass spectrometry.

PMID- 29576707
TI  - Novel Method of Preparation and Activity Research on Arctigenin from Fructus
      Arctii.
AB  - Background: Arctigenin has many pharmacological activities with clinical
      significance and is derived from Arctium lappa L. However, the present extraction
      method is inefficient and does not have meaningful industrial production.
      Objective: A new method to directly prepare arctigenin was established by
      combining enzyme-assisted extraction and central composite design. Arctigenin's
      further pharmacological activity was also surveyed in vitro. Materials and
      Methods: beta-D-Glucosidase, a food-grade enzyme, was added directly to the
      fruits of A. lappa L. to hydrolyze the arctiin to arctigenin, and the obtained
      samples were subsequently subjected to ethanol (30%, v/v) extraction. The
      pharmacological activity of the extraction and arctigenin was determined by
      inhibiting acetylcholinesterase (AChE) and scavenging nitrite. Results: The
      factors investigated include the enzyme concentration (0.5%-2.5%), ultrasound
      time (10 min-3 0 min), and extraction temperature (30 degrees C-50 degrees C).
      From the analysis of the results by Design-Expert (V8.0.6), the optimal
      extraction conditions were obtained: enzyme concentration (1.4%), ultrasound time
      (25 min), and extraction temperature (45 degrees C). The highest yield of
      arctigenin, obtained under the optimal conditions was 6.39%, representing an
      increase of 28.15% compared to the reference extraction without enzyme
      processing. The IC50 values of the extraction and arctigenin, respectively, for
      inhibiting AChE were 0.572 mg/ml and 0.462 mg/ml, and those for nitrite
      scavenging were 34.571 mg/ml and 17.49 mg/ml. Conclusions: The results
      demonstrate that using an enzyme directly in the production is an effective means
      for extracting arctigenin from Fructus arctii. The extraction has the activities
      of inhibiting AChE and scavenging nitrite, probably because there has arctigenin
      in it. It is implied that the extraction and arctigenin could contribute to human
      health in clinical applications. SUMMARY: The new method of adding enzyme
      directly to the preparation of arctigenin was carried out instead of preparing
      arctigenin by two-step methodThree factors affecting the efficiency of
      preparation were analyzed and discussed include the enzyme concentration,
      ultrasound time, and extraction temperature by central composite designThis new
      method of preparing arctigenin improved the yield significantly than other
      methodsArctigenin has remarkable pharmacological activities of inhibiting
      acetylcholinesterase and scavenging nitrite. Abbreviations used: AChE:
      Acetylcholinesterase, CCD: Central composite design, TCM: Traditional Chinese
      medicines, AD.

PMID- 29576709
TI  - Antioxidant and Hemolysis Protective Effects of Polyphenol-Rich Extract from
      Mulberry Fruits.
AB  - Background: Mulberry fruits are a superior source of polyphenol, especially
      anthocyanins that contribute potentially to the beneficial effects which include
      reducing the risk of cardiovascular diseases and cancers with antioxidant, anti
      inflammatory, and chemoprotective properties. Objectives: In this study,
      purification of the polyphenol-rich extract from mulberry fruit (MPE) was
      purified and assessed the activities of antioxidant and hemolysis protective in
      vivo and in vitro. Materials and Methods: Antioxidant activities in vitro was
      measured by quantifying its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging
      activity, reducing power and Fe2+-chelating ability. MPE was purified by high
      pressure liquid chromatography (HPLC) and analyzed individual polyphenols using
      liquid chromatography-mass spectrometry (LC-MS)/MS. Results: The total polyphenol
      content was 147.69 +/- 0.02 mg gallic acid equivalents (GAE)/g dried weight (DW)
      in the extract and 403.55 +/- 0.02 mg GAE/g DW in the purified extract. Further
      identification by HPLC-ultraviolet-visible and LC-MS/MS analysis indicated in
      MPE, an anthocyanin compound, cyanidin-3-O-glucoside. With regard to in vitro
      assays, MPE possessed antioxidant effect, especially in Fe2+ chelating ability
      with an IC50 value of 1.016 mg/mL. The protective effects on mouse red blood cell
      hemolysis and lipid peroxidation ex vivo were dose and time dependent.
      Conclusion: It indicates that MPE could be a good candidate for future biomedical
      applications to promote human health with limited side effects. SUMMARY: Mulberry
      fruit is an excellent source of polyphenols, in particular, anthocyanins, which
      has infinite health benefits. This study determined the predominant anthocyanin,
      cyanidin-3-glucoside, could possibly be the rationale behind the antioxidant and
      antihemolytic effect of MPE. Results indicate that MPE could be a good candidate
      for future biomedical applications to promote human health with limited side
      effects. Abbreviations used: MPE: Purification of the polyphenol-rich extract
      from mulberry fruit, LC-MS: Liquid chromatography-mass spectrometry, HPLC: High
      pressure liquid chromatography, DPPH: 2,2-diphenyl-1-picrylhydrazyl scavenging
      activity, RBC: Red blood cell, GAE: Gallic acid equivalent, FeCl2: Ferrous
      chloride, H2O2: Hydrogen peroxide, EDTA-2Na: Ethylenediaminetetraacetic acid
      disodium salt, PBS: Phosphate-buffered saline, TCA: Trichloroacetic acid, TBA: 2
      thiobarbituric acid, FeSO4: Ferrous sulphate, MDA: Malondialdehyde, VC: Vitamin
      C, DW: Dried weight.

PMID- 29576710
TI  - Capsaicin reverses the inhibitory effect of licochalcone A/beta-Arbutin on
      tyrosinase expression in b16 mouse melanoma cells.
AB  - Introduction: Melanin is synthesized by melanocytes, which are located in the
      basal layer of the skin. After synthesis, melanin is further deposited on the
      surface of the skin to form black spots or chloasma. Tyrosinase is a rate
      limiting enzyme that plays an important role in melanogenesis. Currently, there
      are many drugs that inhibit tyrosinase expression to further reduce
      melanogenesis. Nevertheless, some of these could reverse the pharmacological
      effect of other drugs, when used simultaneously. Materials and Methods: B16 mouse
      melanoma cells were treated with the tyrosinase inhibitors licochalcone A and
      beta-arbutin, alone or in combination with capsaicin, an alkaloid found in
      peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression
      were determined. Results: Licochalcone A/beta-arbutin inhibited tyrosinase
      expression and further hindered melanin synthesis when applied individually to
      B16 mouse melanoma cells. However, licochalcone A/beta-arbutin combined with 50
      MUmol/L capsaicin enhanced the expression of tyrosinase in these cells and
      further increased melanin content. Conclusion: Our data implied that capsaicin
      could reverse the inhibitory effect of licochalcone A/beta-arbutin on tyrosinase
      expression in B16 mouse melanoma cells. SUMMARY: B16 mouse melanoma cells were
      treated with the tyrosinase inhibitors licochalcone A and beta-arbutin, alone or
      in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity,
      melanin content, and tyrosinase activity and expression were determined.
      Licochalcone A/beta-arbutin inhibited tyrosinase expression and further hindered
      melanin synthesis when applied individually to B16 mouse melanoma cells. However,
      licochalcone A/beta-arbutin combined with 50 MUmol/L capsaicin enhanced the
      expression of tyrosinase in these cells and further increased melanin content.
      Our research implied that capsaicin could reverse the inhibitory effect of
      licochalcone A/beta-arbutin on tyrosinase expression in B16 mouse melanoma cells.
      Abbreviations used: B16: B16 mouse melanoma cells; L-DOPA: 3, 4-L
      dihydroxyphenylalanine; TYR: Tyrosinase; USP: United States Pharmacopeia; FBS:
      Fetal bovine serum; EDTA: Ethylenediaminetetraacetic acid; DMSO: Dimethyl
      sulfoxide; RPMI: Roswell Park Memorial Institute; MTT3: 4,5-dimethyl-2-thiazolyl)
      2,5-diphenyl-2-H-tetrazolium bromide, NaOH: Sodium hydroxide; PBS: Phosphate
      buffered saline; RIPA: Radio-immunoprecipitation assay; PMSF:
      Phenylmethanesulfonyl fluoride or phenylmethylsulfonyl fluoride; SDS: Sodium
      dodecyl sulfate, sodium salt; PVDF: Polyvinylidene fluoride; ECL: Enhanced
      chemiluminescence.

PMID- 29576711
TI  - Cordyceps militaris Fraction induces apoptosis and G2/M Arrest via c-Jun N
      Terminal kinase signaling pathway in oral squamous carcinoma KB Cells.
AB  - Background: Cordyceps militaris fraction (CMF) has been shown to possess in vitro
      antitumor activity against human chronic myeloid leukemia K562 cells in our
      previous research. Materials and Methods: The in vitro inhibitory activities of
      CMF on the growth of KB cells were evaluated by viability assay. The apoptotic
      and cell cycle influences of CMF were detected by 4',6-diamidino-2-phenylindole
      staining and flow cytometry assay. The expression of different apoptosis
      associated proteins and cell cycle regulatory proteins was examined by Western
      blot assay. The nuclear localization of c-Jun was observed by fluorescence
      staining. Objective: The objective of this study was to investigate the
      antiproliferative effect of CMF as well as the mechanism underlying the apoptosis
      and cell cycle arrest it induces in KB cells. Results: CMF suppressed KB cells'
      proliferation in a dose- and time-dependent manner. Flow cytometric analysis
      indicated that CMF induced G2/M cell cycle arrest and apoptosis. Western blot
      analysis revealed that CMF induced caspase-3, caspase-9, and PARP cleavages, and
      increased the Bax/Bcl-2 ratio. CMF also led to increased expression of p21,
      decreased expression of cyclin B1, mitotic phosphatase cdc25c, and mitotic kinase
      cdc2, as well as unchanged expression of p53. In addition, CMF stimulated c-Jun N
      terminal kinases (JNK) protein phosphorylations, resulting in upregulated
      expression of c-Jun and nuclear localization of c-Jun. Pretreatment with JNK
      inhibitor SP600125 suppressed CMF-induced apoptosis and G2/M arrest. Conclusions:
      CMF is capable of modulating c-Jun caspase and Bcl-2 family proteins through JNK
      dependent apoptosis, which results in G2/M phase arrest in KB cells. CMF could be
      developed as a promising candidate for the new antitumor agents. SUMMARY: CMF
      exhibited strong anticancer activity against oral squamous carcinoma KB cellsCMF
      inhibited KB cells' proliferation via induction of apoptosis and G2/M cell cycle
      arrestCMF activated JNK signaling pathway and promoted the nuclear localization
      of c-JunCMF regulated the apoptosis- and cell cycle-related proteins in a manner
      dependent on JNK/c-Jun pathway. Abbreviations used: CMF: Cordyceps militaris
      fraction; OSCC: Oral squamous cell carcinoma; JNK: c-Jun N-terminal kinase.

PMID- 29576712
TI  - Computational tool for immunotoxic assessment of pyrethroids toward adaptive
      immune cell receptors.
AB  - Background: Pyrethroids have prominently known for their insecticidal actions
      worldwide, but recent reports as anticancer and antiviral applications gained a
      lot of interest to further understand their safety and immunotoxicity. Objective:
      This encouraged us to carry out our present study to evaluate the interactions of
      pyrethroids toward adaptive immune cell receptors. Materials and Methods: Type 1
      and Type 2 pyrethroids were tested on T (CD4 and CD8) and B (CD28 and CD45)
      immune cell receptors using Maestro 9.3 (Schrodinger, LLC, Cambridge, USA). In
      addition, top-ranked tested ligands were too explored for toxicity prediction in
      rodents using ProTOX tool. Results: Pyrethroids (specifically type 2) such as
      fenvalerate (-5.534 kcal/mol: CD8), fluvalinate (-4.644 and - 4.431 kcal/mol: CD4
      and CD45), and cypermethrin (-3.535 kcal/mol: CD28) have outcome in less energy
      or more affinity for B-cell and T-cell immune receptors which may later result in
      the immunosuppressive and hypersensitivity reactions. Conclusion: The current
      findings have uncovered that there is a further need to assess the Type 2
      pyrethroids with wet laboratory experiments to understand the chemical nature of
      pyrethroid-induced immunotoxicity. SUMMARY: Fenvalerate showed apex glide score
      toward CD8 immune receptor, while fluvalinate confirmed top-ranked binding with
      CD4 and CD45 immune proteinsIn addition, cypermethrin outcame in top glide score
      against CD28 immune receptorTop dock hits (Type 2) pyrethroids have shown
      probable toxicity targets toward AOFA: Amine oxidase (flavin-containing) A and
      PGH1: Prostaglandin G/H synthase 1, respectively. Abbreviations used: PDB:
      Protein Data Bank; AOFA: Amine oxidase (flavin-containing) A; PGH 1:
      Prostaglandin G/H synthase 1.

PMID- 29576713
TI  - Determination of Eupatilin in Folium artemisiae Argyi and Its Inhibitory Effect
      on Hepatoma Cells.
AB  - Aim: The aim of this study is to establish a method for determination of
      eupatilin in Folium artemisiae Argyi and observe the inhibitory effect of Folium
      artemisiae Argyi extract on human hepatoma SMMC-7721 cells. Methods: High
      performance liquid chromatograph system with 2910 pump, 2930 UV detector, and
      N2000 workstation was used for determination of eupatilin in Folium artemisiae
      Argyi. Human hepatoma SMMC-7721 cells were cultured and cell proliferation was
      measured using the MTT assay. The expression protein levels of p53, Topo II, and
      bcl-2 were detected using Western blotting. Results: Eupatilin exhibited a
      linearity range of 0.5-3.0 MUg/mL and a recovery of 100.72%, relevant standard
      derivation = 2.28%. Folium artemisiae Argyi extract had marked cytostatic and
      cytotoxic effects on SMMC-7721 cells, inhibited the SMMC-7721 colony formation in
      a dose-dependent manner. Folium artemisiae Argyi extract already possessed
      delayed effect after treating SMMC-7721 cells for 8 h, which became obvious at 12
      h from treatment. After drug withdrawal, cells still tended to apoptosis. Folium
      artemisiae Argyi extract could inhibit p53, Topo II, and bcl-2 expressions in
      tumor cells. The present method for determination of eupatilin is simple, fast,
      accurate, sensitive, and reproducible. Conclusion: Hepatoma SMMC-7721 cells are
      quite sensitive to Folium artemisiae Argyi extract, which may be associated with
      its suppression of p53, Topo II, and bcl-2 expressions. SUMMARY: The study aimed
      to establish a method for determination of eupatilin in Folium artemisiae Argyi
      and observe the inhibitory effect of Folium artemisiae Argyi extract on human
      hepatoma SMMC-7721 cells. The results suggested that the present method for
      determination of eupatilin is simple, fast, accurate, sensitive, and
      reproducible. Hepatoma SMMC-7721 cells are quite sensitive to Folium artemisiae
      Argyi extract, which may be associated with its suppression of p53, Topo II, and
      bcl-2 expressions. Abbreviations used: HPLC: High-performance liquid
      chromatograph; OD: Optical density; RSD: Relevant standard derivation; IC50:
      Inhibitory 50% concentration.

PMID- 29576716
TI  - Sparse signals recovered by non-convex penalty in quasi-linear systems.
AB  - The goal of compressed sensing is to reconstruct a sparse signal under a few
      linear measurements far less than the dimension of the ambient space of the
      signal. However, many real-life applications in physics and biomedical sciences
      carry some strongly nonlinear structures, and the linear model is no longer
      suitable. Compared with the compressed sensing under the linear circumstance,
      this nonlinear compressed sensing is much more difficult, in fact also NP-hard,
      combinatorial problem, because of the discrete and discontinuous nature of the
      [Formula: see text]-norm and the nonlinearity. In order to get a convenience for
      sparse signal recovery, we set the nonlinear models have a smooth quasi-linear
      nature in this paper, and study a non-convex fraction function [Formula: see
      text] in this quasi-linear compressed sensing. We propose an iterative fraction
      thresholding algorithm to solve the regularization problem [Formula: see text]
      for all [Formula: see text]. With the change of parameter [Formula: see text],
      our algorithm could get a promising result, which is one of the advantages for
      our algorithm compared with some state-of-art algorithms. Numerical experiments
      show that our method performs much better than some state-of-the-art methods.

PMID- 29576715
TI  - Positive periodic solution for p-Laplacian neutral Rayleigh equation with
      singularity of attractive type.
AB  - In this paper, we consider a kind of p-Laplacian neutral Rayleigh equation with
      singularity of attractive type, [Formula: see text] By applications of an
      extension of Mawhin's continuation theorem, sufficient conditions for the
      existence of periodic solution are established.

PMID- 29576714
TI  - Rhubarb attenuates cerebral edema via inhibition of the extracellular signal
      regulated kinase pathway following traumatic brain injury in rats.
AB  - Background: Rhubarb is a traditional Chinese medicine for treating traumatic
      brain injury (TBI). Purpose: The purpose of this study is to elucidate the
      potential mechanism of rhubarb by suppressing extracellular signal-regulated
      kinase (ERK) to ameliorate brain edema. Materials and Methods: Sprague-Dawley
      rats were separated into four groups at random. One group received 3 g/kg
      rhubarb, and another group received 12 g/kg rhubarb, and the vehicle group and
      sham group were administered the same dose of saline solution. The blood-brain
      barrier disruption and edema were detected by Evans blue extravasation and water
      content, respectively. ERK, Matrix metalloproteinase 9 (MMP-9), and zonula
      occluden-1 (ZO-1) in the damaged tissue were measured by western blot analysis
      and quantitative real-time polymerase chain reaction. Results: Rhubarb attenuated
      the brain edema after TBI, especially at the dose of 12 g/kg. Rhubarb
      significantly suppressed ERK, down-regulated MMP-9, and up-regulated ZO-1.
      Rhubarb might be a prospective therapeutic regimen to decrease edema in TBI.
      Conclusions: Rhubarb alleviates the edema by restraining the ERK signaling
      pathway. Our results contribute to the validation of the traditional use of
      rhubarb in the treatment of TBI and its mechanism. SUMMARY: The aim of this study
      was to explore the potential mechanism of rhubarb by suppressing extracellular
      signal-regulated kinase to ameliorate brain edema. Results: Rhubarb ameliorates
      edema caused by traumatic brain injury by inhibiting the ERK/Matrix
      metalloproteinase 9/zonula occluden-1 signaling pathway. Abbreviations used: TBI:
      Traumatic brain injury, ERK: Extracellular signal-regulated kinase pathway, MMP
      9: Matrix metalloproteinase 9, ZO-1: Zonula occluden-1, BBB: Blood-brain barrier,
      PCR: Polymerase chain reaction, TCM: Traditional Chinese medicine, MAPKs: Mitogen
      activated protein kinases, CCI: Controlled cortical impact, DL: Rhubarb 3 g/kg in
      distilled water, DH: Rhubarb 12 g/kg in distilled water, EB: Evans blue, IOD:
      Integral optical density, MEK: Mitogen extracellular kinase, MMPs: Matrix
      metalloproteinases, NADPH: Nicotinamide adenine dinucleotide phosphate: ROS,
      reactive oxygen species.

PMID- 29576717
TI  - A new error estimate on uniform norm of Schwarz algorithm for elliptic quasi
      variational inequalities with nonlinear source terms.
AB  - The Schwarz algorithm for a class of elliptic quasi-variational inequalities with
      nonlinear source terms is studied in this work. The authors prove a new error
      estimate in uniform norm, making use of a stability property of the discrete
      solution. The domain is split into two sub-domains with overlapping non-matching
      grids. This approach combines the geometrical convergence of solutions and the
      uniform convergence of variational inequalities.

PMID- 29576718
TI  - Approximation properties of lambda-Bernstein operators.
AB  - In this paper, we introduce a new type lambda-Bernstein operators with parameter
      [Formula: see text], we investigate a Korovkin type approximation theorem,
      establish a local approximation theorem, give a convergence theorem for the
      Lipschitz continuous functions, we also obtain a Voronovskaja-type asymptotic
      formula. Finally, we give some graphs and numerical examples to show the
      convergence of [Formula: see text] to [Formula: see text], and we see that in
      some cases the errors are smaller than [Formula: see text] to f.

PMID- 29576719
TI  - Some limit theorems for weighted negative quadrant dependent random variables
      with infinite mean.
AB  - In the present paper, we will investigate weak laws of large numbers for weighted
      pairwise NQD random variables with infinite mean. The almost sure upper and lower
      bounds for a particular normalized weighted sum of pairwise NQD nonnegative
      random variables are established also.

PMID- 29576720
TI  - Synthesis, molecular docking, ctDNA interaction, DFT calculation and evaluation
      of antiproliferative and anti-Toxoplasma gondii activities of 2,4-diaminotriazine
      thiazole derivatives.
AB  - Synthesis, characterization, and investigation of antiproliferative activities
      against human cancer cell lines (MV4-11, MCF-7, and A549) and Toxoplasma gondii
      parasite of twelve novel 2,4-diaminotriazine-thiazoles are presented. The
      toxicity of the compounds was studied at three different cell types, normal mouse
      fibroblast (Balb/3T3), mouse fibroblast (L929), and human VERO cells. The
      structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS,
      and elemental analyses. Among the derivatives, 4a-k showed very high activity
      against MV4-11 cell line with IC50 values between 1.13 and 3.21 ug/ml.
      Additionally, the cytotoxic activity of compounds 4a-k against normal mouse
      fibroblast Balb/3T3 cells is about 20-100 times lower than against cancer cell
      lines. According to our results, compounds 4a, 4b, 4d, and 4i have very strong
      activity against human breast carcinoma MCF-7, with IC50 values from 3.18 to 4.28
      ug/ml. Moreover, diaminotriazines 4a-l showed significant anti-Toxoplasma gondii
      activity, with IC50 values 9-68 times lower than those observed for sulfadiazine.
      Molecular docking studies indicated DNA-binding site of hTopoI and hTopoII as
      possible anticancer targets and purine nucleoside phosphorylase as possible anti
      toxoplasmosis target. Our UV-Vis spectroscopic results indicate also that
      diaminotriazine-thiazoles tends to interact with DNA by intercalation.
      Additionally, the structure and the interaction and binding energies of a model
      complex formed by compound 4a and two thymine molecules are investigated using
      quantum mechanical methods.

PMID- 29576722
TI  - Structural Factors of Elders' Isolation in a High-Crime Neighborhood: An In-Depth
      Perspective.

PMID- 29576723
TI  - A Pilot Study Examining the Effectiveness of the PEERS Program on Social Skills
      and Anxiety in Adolescents with Autism Spectrum Disorder.
AB  - The Program for the Evaluation of the Enrichment of Relational Skills (PEERS), a
      social skills intervention for high functioning adolescents with autism spectrum
      disorder (ASD), has been proven efficacious in randomized control trials.
      However, the effectiveness of the PEERS program in community settings has not
      been studied. The present small-scale pilot study examined the effectiveness of
      the PEERS program in a community setting. Five adolescents and their caregivers
      participated in the PEERS intervention. Results indicated that the adolescents
      showed significant improvement in their social engagement, social cognition,
      social communication, social motivation, and knowledge of PEERS skills and
      concepts from pre- to post-intervention. Furthermore, adolescents showed
      significant reductions in their internalizing and autistic symptoms from pre- to
      post-intervention. The findings from this small-scale pilot study support the
      effectiveness of the PEERS program in community-based settings.

PMID- 29576721
TI  - Comparative molecular field analysis and molecular dynamics studies of the
      dopamine D2 receptor antagonists without a protonatable nitrogen atom.
AB  - The dopaminergic hypothesis of schizophrenia is the main concept explaining the
      direct reasons of schizophrenia and the effectiveness of current antipsychotics.
      All antipsychotics present on the market are potent dopamine D2 receptor
      antagonists or partial agonists. In this work we investigate a series of dopamine
      D2 receptor antagonists which do not fulfill the criteria of the classical
      pharmacophore model as they do not possess a protonatable nitrogen atom necessary
      to interact with the conserved Asp(3.32). Such compounds are interesting, inter
      alia, due to possible better pharmacokinetic profile when compared to basic,
      ionizable molecules. By means of homology modeling, molecular docking and
      molecular dynamics we determined that the compounds investigated interact with
      Asp(3.32) via their amide nitrogen atom. It was found that the studied compounds
      stabilize the receptor inactive conformation through the effect on the ionic
      lock, which is typical for GPCR antagonists. We constructed a CoMFA model for the
      studied compounds with the following statistics: R2 = 0.95, Q2 = 0.63. The
      quality of the CoMFA model was confirmed by high value of R2 of the test set,
      equal 0.96. The CoMFA model indicated two regions where bulky substituents are
      favored and two regions where bulky substituents are not beneficial. Two red
      contour regions near carbonyl groups were identified meaning that negative charge
      would be favored here. Furthermore, the S-oxide group is connected with blue
      contour region meaning that positive charge is favored in this position. These
      findings may be applied for further optimization of the studied compound series.

PMID- 29576724
TI  - Internationalized at work and localistic at home: The 'split' Europeanization
      behind Brexit.
AB  - This paper looks at the results of the referendum on the United Kingdom
      membership to the European Union in order to test the link between the
      internationalization of the local economy and the openness of the local society
      as factors associated with the Leave vote (Brexit). The paper compares a number
      of alternative explanations put forward in the public debate after the
      referendum. The empirical analysis suggests that the outcome of the referendum
      can be linked to an increasing tension between the ever increasing
      internationalization of local firms and the 'localistic' attitude of their
      employees. Brexit can be seen as the result of a process of 'split
      Europeanization' whereby Euroscepticism is triggered by the increasing mismatch
      between internationalized economies (and corporate economic interests) and
      localistic societies (and workers' attitudes and cultural preferences).

PMID- 29576725
TI  - Are There Gender Differences in Emotion Comprehension? Analysis of the Test of
      Emotion Comprehension.
AB  - This article examines whether there are gender differences in understanding the
      emotions evaluated by the Test of Emotion Comprehension (TEC). The TEC provides a
      global index of emotion comprehension in children 3-11 years of age, which is the
      sum of the nine components that constitute emotion comprehension: (1) recognition
      of facial expressions, (2) understanding of external causes of emotions, (3)
      understanding of desire-based emotions, (4) understanding of belief-based
      emotions, (5) understanding of the influence of a reminder on present emotional
      states, (6) understanding of the possibility to regulate emotional states, (7)
      understanding of the possibility of hiding emotional states, (8) understanding of
      mixed emotions, and (9) understanding of moral emotions. We used the answers to
      the TEC given by 172 English girls and 181 boys from 3 to 8 years of age. First,
      the nine components into which the TEC is subdivided were analysed for
      differential item functioning (DIF), taking gender as the grouping variable. To
      evaluate DIF, the Mantel-Haenszel method and logistic regression analysis were
      used applying the Educational Testing Service DIF classification criteria. The
      results show that the TEC did not display gender DIF. Second, when absence of DIF
      had been corroborated, it was analysed for differences between boys and girls in
      the total TEC score and its components controlling for age. Our data are
      compatible with the hypothesis of independence between gender and level of
      comprehension in 8 of the 9 components of the TEC. Several hypotheses are
      discussed that could explain the differences found between boys and girls in the
      belief component. Given that the Belief component is basically a false belief
      task, the differences found seem to support findings in the literature indicating
      that girls perform better on this task.

PMID- 29576726
TI  - Evaluation of a Train-The-Trainers Model for Family Peer Advocates in Children's
      Mental Health.
AB  - Standardized training and credentialing is increasingly important to states and
      healthcare systems. Workforce shortages in children's mental health can be
      addressed through training and credentialing of professional peer parents (called
      family peer advocates or FPAs), who deliver a range of services to caregivers. A
      theory-based training program for FPAs targeting skills and knowledge about
      childhood mental health services (Parent Empowerment Program, or PEP) was
      developed through a partnership among a statewide family-run organization, state
      policy leaders, and academic researchers. Prior studies by this team using highly
      experienced family peer advocates (who were also co-developers of the training
      program) as trainers found improvements in knowledge about mental health services
      and self-efficacy. In 2010, to meet demands and scale the model, a training of
      trainers (TOT) model was developed to build a cohort of locally-trained FPAs to
      deliver PEP training. A pre/post design was used to evaluate the impact of TOT
      model on knowledge and self-efficacy among 318 FPAs across the state.
      Participants showed significant pre-post (6 month) changes in knowledge about
      mental health services and self-efficacy. There were no significant associations
      between any FPA demographic characteristics and their knowledge or self-efficacy
      scores. A theory-based training model for professional peer parents working in
      the children's mental health system can be taught to local FPAs, and it improves
      knowledge about the mental health system and self-efficacy. Studies that evaluate
      the effectiveness of different training modalities are critical to ensure that
      high-quality trainings are maintained.

PMID- 29576727
TI  - Similarities and Differences in the Psychosocial Development of Children Placed
      in Different 24-h Settings.
AB  - Similarities and differences in the (short-term) psychosocial development of
      children in foster care, family-style group care, and residential care were
      investigated in a sample of 121 Dutch children (M age = 8.78 years; SD = 2.34
      years; 47% female; 59% Caucasian) one year after their initial placement. Pretest
      and posttest measurements were carried out at the substitute caregivers using the
      CBCL. The results were examined at group level and case level. At group level,
      the findings showed no evidence for higher effectiveness in favor to the family
      oriented settings (foster care, and family-style group care), as hypothesized. By
      contrast, some small differences were found between foster care and family-style
      group care, in favor of the latter. At individual level, a more or less equal
      number of children (18%) with a clinical pretest score on psychosocial
      functioning clinically significant improved (behavioral normalization). An
      important concern is that a number of children without clinical psychosocial
      problems at the time of admission clinically significant deteriorated (behavioral
      aberration) in psychosocial functioning (20%). This might indicate a poor match
      between the risks, needs and responsivity of the child on the one hand and the
      chosen intervention on the other. Future research on factors that (prior and
      during placement) positively as well as negatively affect the child's
      psychosocial development is needed to further clarify this finding.

PMID- 29576728
TI  - Psychosocial Needs of Children in Foster Care and the Impact of Sexual Abuse.
AB  - Children in family foster care, especially those who have experienced sexual
      abuse, require a safe and nurturing environment in which their psychosocial needs
      are met. However, there is limited knowledge on how youth prioritize various
      needs and what impact previous experiences have on these needs. In this study, we
      asked youth (formerly) in family foster care to indicate their psychosocial
      needs, and analyzed if youth with a history of sexual abuse have different needs.
      A Q methodological study was conducted with 44 youth (age 16-28). Fifteen of them
      reported sexual abuse during their childhood. Using by-person factor analyses,
      respondents who share similar subjective views were grouped together. Qualitative
      interpretations of the factors show differences and similarities between and
      within the two groups, related to help from others, being independent, processing
      the past, and working toward the future. Although the needs of youth with and
      without experiences of sexual abuse seem mostly similar, one group of sexually
      abused youth specifically indicated not wanting an emotional connection to foster
      parents, but instead a strictly instrumental, professional relationship. This
      study captured the diverse perspectives of youth themselves, revealing that
      children in foster care differ with regard to what they consider as (most)
      important safety, belonging, self-esteem and self-actualization needs.

PMID- 29576729
TI  - Likelihood-based confidence intervals for a parameter with an upper or lower
      bound.
AB  - The precision of estimates in many statistical models can be expressed by a
      confidence interval (CI). CIs based on standard errors (SE) are common in
      practice, but likelihood-based CIs are worth consideration. In comparison to SEs,
      likelihood-based CIs are typically more difficult to estimate, but are more
      robust to model (re)parameterization. In latent variable models, some parameters
      may take on values outside of their interpretable range. Therefore, it is
      desirable to place a bound to keep the parameter interpretable. For likelihood
      based CI, a correction is needed when a parameter is bounded. The correction is
      known (Wu & Neale, 2012), but is difficult to implement in practice. A novel
      automatic implementation that is simple for an applied researcher to use is
      introduced. A simulation study demonstrates the accuracy of the correction using
      a latent growth curve model and the method is illustrated with a multilevel
      confirmatory factor analysis.

PMID- 29576730
TI  - Developing a Multi-Dimensional Early Elementary Mathematics Screener and
      Diagnostic Tool: The Primary Mathematics Assessment.
AB  - There is a critical need to identify primary level students experiencing
      difficulties in mathematics to provide immediate and targeted instruction that
      remediates their deficits. However, most early math screening instruments focus
      only on the concept of number, resulting in inadequate and incomplete information
      for teachers to design intervention efforts. We propose a mathematics assessment
      that screens and provides diagnostic information in six domains that are
      important to building a strong foundation in mathematics. This article describes
      the conceptual framework and psychometric qualities of a web-based assessment
      tool, the Primary Math Assessment (PMA). The PMA includes a screener to identify
      students at risk for poor math outcomes and a diagnostic tool to provide a more
      in-depth profile of children's specific strengths and weaknesses in mathematics.
      The PMA allows teachers and school personnel to make better instructional
      decisions by providing more targeted analyses.

PMID- 29576732
TI  - HIV-related sexual decisions made by African-American adolescents living in
      different family structures: study from an ecodevelopmental perspective.
AB  - Purpose: The purpose of this study was to explore the association between the
      dynamics of family structure and sexual behaviors of African-American adolescents
      using the ecodevelopmental theory. Methods: This study stratified data from 1,617
      African-American adolescents of the Add Health Wave I respondents with an
      identified family composition. It examined the associations between family
      structure, parenting function, and adolescents' sexual decision-making: age of
      first sexual intercourse, sexual initiation before age 16, and using a condom
      during the first and last sexual intercourse. Results: Emotional connection
      between parents and children (feeling more love from the father: beta=0.17,
      P=0.0312; feeling more love from the mother: beta=0.3314, P=0.0420) and mothers'
      less permissive attitude toward adolescents' sexual experience in their teens
      (beta=0.33, P=0.0466) are positively associated with late age of sexual
      initiation of adolescents living in two-parent households. School-level factors
      (beta=0.07, P=0.0008) and the adolescents' characteristics (being older: 0.42,
      P=0.0002; heterosexuality: beta=2.28, P=0.0091) are the factors most positively
      related to the age of sexual initiation for those living with a single parent.
      Immediate social determinants, other than family factors (such as land use of
      immediate area [rural]: beta=9.84, P<0.0001; the condition of living unit:
      beta=1.55, P=0.0011; and safety of neighborhood: beta=4.46, P=0.004), are related
      to late age of sexual initiation among those living with other relatives/alone. A
      higher tendency of condom use consistency was present in adolescents living with
      two parents compared to those living in other family structures. Conclusion: Less
      parent/child connection and parent/family influence were found in African
      American adolescents living with other relatives or alone, suggesting that living
      with two residential parents plays an essential role in their late sexual
      initiation and could account for an important element to combat high HIV
      incidence of African-American adolescents.

PMID- 29576731
TI  - Aggressiveness, violence, homicidality, homicide, and Lyme disease.
AB  - Background: No study has previously analyzed aggressiveness, homicide, and Lyme
      disease (LD). Materials and methods: Retrospective LD chart reviews analyzed
      aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and
      analyzed homicides. Results: Most aggression with LD was impulsive, sometimes
      provoked by intrusive symptoms, sensory stimulation or frustration and was
      invariably bizarre and senseless. About 9.6% of LD patients were homicidal with
      the average diagnosis delay of 9 years. Postinfection findings associated with
      homicidality that separated from the non-homicidal group within the 95%
      confidence interval included suicidality, sudden abrupt mood swings, explosive
      anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition,
      nightmares, depersonalization, intrusive aggressive images, dissociative
      episodes, derealization, intrusive sexual images, marital/family problems, legal
      problems, substance abuse, depression, panic disorder, memory impairments,
      neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides
      included predatory aggression, poor impulse control, and psychosis. Some patients
      have selective hyperacusis to mouth sounds, which I propose may be the result of
      brain dysfunction causing a disinhibition of a primitive fear of oral predation.
      Conclusion: LD and the immune, biochemical, neurotransmitter, and the neural
      circuit reactions to it can cause impairments associated with violence. Many LD
      patients have no aggressiveness tendencies or only mild degrees of low
      frustration tolerance and irritability and pose no danger; however, a lesser
      number experience explosive anger, a lesser number experience homicidal thoughts
      and impulses, and much lesser number commit homicides. Since such large numbers
      are affected by LD, this small percent can be highly significant. Much of the
      violence associated with LD can be avoided with better prevention, diagnosis, and
      treatment of LD.

PMID- 29576733
TI  - Spotlight on daytime napping during early childhood.
AB  - Daytime napping undergoes a remarkable change in early childhood, and research
      regarding its relationship to cognitive development has recently accelerated. In
      this review, we summarize our current understanding of this relationship focusing
      on children aged <5 years. First, we evaluate different studies on the basis of
      the experimental design used and the specific cognitive processes they
      investigate. Second, we analyze how the napping status of children may modulate
      the relationship between learning and napping. Third, the possible role of sleep
      spindles, ie, specific electroencephalographic components during sleep, in
      cognitive development is explored. We conclude that daytime napping is crucial in
      early memory development.

PMID- 29576734
TI  - Impact of preferential sampling on exposure prediction and health effect
      inference in the context of air pollution epidemiology.
AB  - Preferential sampling has been defined in the context of geostatistical modeling
      as the dependence between the sampling locations and the process that describes
      the spatial structure of the data. It can occur when networks are designed to
      find high values. For example, in networks based on the U.S. Clean Air Act
      monitors are sited to determine whether air quality standards are exceeded. We
      study the impact of the design of monitor networks in the context of air
      pollution epidemiology studies. The effect of preferential sampling has been
      illustrated in the literature by highlighting its impact on spatial predictions.
      In this paper, we use these predictions as input in a second stage analysis, and
      we assess how they affect health effect inference. Our work is motivated by data
      from two United States regulatory networks and health data from the Multi-Ethnic
      Study of Atherosclerosis and Air Pollution. The two networks were designed to
      monitor air pollution in urban and rural areas respectively, and we found that
      the health analysis results based on the two networks can lead to different
      scientific conclusions. We use preferential sampling to gain insight into these
      differences. We designed a simulation study, and found that the validity and
      reliability of the health effect estimate can be greatly affected by how we
      sample the monitor locations. To better understand its effect on second stage
      inference, we identify two components of preferential sampling that shed light on
      how preferential sampling alters the properties of the health effect estimate.

PMID- 29576735
TI  - Functional inverted Wishart for Bayesian multivariate spatial modeling with
      application to regional climatology model data.
AB  - Modern environmental and climatological studies produce multiple outcomes at high
      spatial resolutions. Multivariate spatial modeling is an established means to
      quantify cross-correlation among outcomes. However, existing models typically
      suffer from poor computational efficiency and lack the flexibility to
      simultaneously estimate auto- and cross-covariance structures. In this article,
      we undertake a novel construction of covariance by utilizing spectral convolution
      and by imposing an inverted Wishart prior on the cross-correlation structure. The
      cross-correlation structure with this functional inverted Wishart prior flexibly
      accommodates not only positive but also weak or negative associations among
      outcomes while preserving spatial resolution. Furthermore, the proposed model is
      computationally efficient and produces easily interpretable results, including
      the individual autocovariances and full cross-correlation matrices, as well as a
      partial cross-correlation matrix reflecting the outcome correlation after
      excluding the effects caused by spatial convolution. The model is examined using
      simulated data sets under different scenarios. It is also applied to the data
      from the North American Regional Climate Change Assessment Program, examining
      long-term associations between surface outcomes for air temperature, pressure,
      humidity, and radiation, on the land area of the North American West Coast.
      Results and predictive performance are compared with findings from approaches
      using convolution only or coregionalization.

PMID- 29576736
TI  - Testing for Marginal Linear Effects in Quantile Regression.
AB  - This paper develops a new marginal testing procedure to detect the presence of
      significant predictors associated with the conditional quantiles of a scalar
      response. The idea is to fit the marginal quantile regression on each predictor
      one at a time, and then base the test on the t-statistics associated with the
      most predictive predictors. A resampling method is devised to calibrate this test
      statistic, which has non-regular limiting behavior due to the selection of the
      most predictive variables. Asymptotic validity of the procedure is established in
      a general quantile regression setting in which the marginal quantile regression
      models can be misspecified. Even though a fixed dimension is assumed to derive
      the asymptotic results, the proposed test is applicable and computationally
      feasible for large-dimensional predictors. The method is more flexible than
      existing marginal screening test methods based on mean regression, and has the
      added advantage of being robust against outliers in the response. The approach is
      illustrated using an application to an HIV drug resistance dataset.

PMID- 29576737
TI  - Subnanogram proteomics: impact of LC column selection, MS instrumentation and
      data analysis strategy on proteome coverage for trace samples.
AB  - One of the greatest challenges for mass spectrometry (MS)-based proteomics is the
      limited ability to analyze small samples. Here we investigate the relative
      contributions of liquid chromatography (LC), MS instrumentation and data analysis
      methods with the aim of improving proteome coverage for sample sizes ranging from
      0.5 ng to 50 ng. We show that the LC separations utilizing 30-MUm-i.d. columns
      increase signal intensity by >3-fold relative to those using 75-MUm-i.d. columns,
      leading to 32% increase in peptide identifications. The Orbitrap Fusion Lumos MS
      significantly boosted both sensitivity and sequencing speed relative to earlier
      generation Orbitraps (e.g., LTQ-Orbitrap), leading to a ~3-fold increase in
      peptide identifications and 1.7-fold increase in identified protein groups for 2
      ng tryptic digests of the bacterium S. oneidensis. The Match Between Runs
      algorithm of open-source MaxQuant software further increased proteome coverage by
      ~ 95% for 0.5 ng samples and by ~42% for 2 ng samples. Using the best combination
      of the above variables, we were able to identify >3,000 proteins from 10 ng
      tryptic digests from both HeLa and THP-1 mammalian cell lines. We also identified
      >950 proteins from subnanogram archaeal/bacterial cocultures. The present
      ultrasensitive LC-MS platform achieves a level of proteome coverage not
      previously realized for ultra-small sample loadings, and is expected to
      facilitate the analysis of subnanogram samples, including single mammalian cells.

PMID- 29576738
TI  - Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha
      radionuclide therapy.
AB  - The 225Ac radioisotope exhibits very attractive nuclear properties for
      application in radionuclide therapy. Unfortunately, the major challenge for
      radioconjugates labelled with 225Ac is that traditional chelating moieties are
      unable to sequester the radioactive daughters in the bioconjugate which is
      critical to minimize toxicity to healthy, non-targeted tissues. In the present
      work, we propose to apply TiO2 nanoparticles (NPs) as carrier for 225Ac and its
      decay products. The surface of TiO2 nanoparticles with 25 nm diameter was
      modified with Substance P (5-11), a peptide fragment which targets NK1 receptors
      on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles
      functionalized with Substance P (5-11) were synthesized with high yield in a two
      step procedure, and the products were characterized by transmission electron
      microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis
      (TGA). The obtained results show that one TiO2-bioconjugate nanoparticle contains
      in average 80 peptide molecules on its surface. The synthesized TiO2-PEG-SP(5-11)
      conjugates were labelled with 225Ac by ion-exchange reaction on hydroxyl (OH)
      functional groups on the TiO2 surface. The labelled bioconjugates almost
      quantitatively retain 225Ac in phosphate-buffered saline (PBS), physiological
      salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of 221Fr, a
      first decay daughter of 225Ac, in an amount of 30% was observed only in CSF after
      10 days. The synthesized 225Ac-TiO2-PEG-SP(5-11) has shown high cytotoxic effect
      in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate
      for targeted radionuclide therapy of brain tumours.

PMID- 29576739
TI  - Tests of chameleon gravity.
AB  - Theories of modified gravity, where light scalars with non-trivial self
      interactions and non-minimal couplings to matter-chameleon and symmetron theories
      dynamically suppress deviations from general relativity in the solar system. On
      other scales, the environmental nature of the screening means that such scalars
      may be relevant. The highly-nonlinear nature of screening mechanisms means that
      they evade classical fifth-force searches, and there has been an intense effort
      towards designing new and novel tests to probe them, both in the laboratory and
      using astrophysical objects, and by reinterpreting existing datasets. The results
      of these searches are often presented using different parametrizations, which can
      make it difficult to compare constraints coming from different probes. The
      purpose of this review is to summarize the present state-of-the-art searches for
      screened scalars coupled to matter, and to translate the current bounds into a
      single parametrization to survey the state of the models. Presently, commonly
      studied chameleon models are well-constrained but less commonly studied models
      have large regions of parameter space that are still viable. Symmetron models are
      constrained well by astrophysical and laboratory tests, but there is a desert
      separating the two scales where the model is unconstrained. The coupling of
      chameleons to photons is tightly constrained but the symmetron coupling has yet
      to be explored. We also summarize the current bounds on f(R) models that exhibit
      the chameleon mechanism (Hu and Sawicki models). The simplest of these are well
      constrained by astrophysical probes, but there are currently few reported bounds
      for theories with higher powers of R. The review ends by discussing the future
      prospects for constraining screened modified gravity models further using
      upcoming and planned experiments.

PMID- 29576740
TI  - How to Synthesise High Purity, Crystalline d-Glucaric Acid Selectively.
AB  - Glucaric acid has potential applications in food, pharmaceutical and polymer
      industries yet no methodology exists within the public domain for isolation of
      this key bio-derived platform molecule as a pure, crystalline solid. Here we
      demonstrate the difficulties, which arise in doing so and report development of a
      process for derivation of free-glucaric acid from its Ca2+/K+ glucarate salts,
      which are both commercially available. Employing Amberlyst-15 (H+) exchange resin
      and azeotrope drying, powdered glucaric acid is prepared at > 99.96 % purity in
      98.7 % dry yield.

PMID- 29576741
TI  - f(R) gravity modifications: from the action to the data.
AB  - It is a very well established matter nowadays that many modified gravity models
      can offer a sound alternative to General Relativity for the description of the
      accelerated expansion of the universe. But it is also equally well known that no
      clear and sharp discrimination between any alternative theory and the classical
      one has been found so far. In this work, we attempt at formulating a different
      approach starting from the general class of f(R) theories as test probes: we try
      to reformulate f(R) Lagrangian terms as explicit functions of the redshift, i.e.,
      as f(z). In this context, the f(R) setting to the consensus cosmological model,
      the [Formula: see text]CDM model, can be written as a polynomial including just a
      constant and a third-order term. Starting from this result, we propose various
      different polynomial parameterizations f(z), including new terms which would
      allow for deviations from [Formula: see text]CDM, and we thoroughly compare them
      with observational data. While on the one hand we have found no statistically
      preference for our proposals (even if some of them are as good as [Formula: see
      text]CDM by using Bayesian Evidence comparison), we think that our novel approach
      could provide a different perspective for the development of new and
      observationally reliable alternative models of gravity.

PMID- 29576742
TI  - High life expectancy and reversed socioeconomic gradients of elderly people in
      Mexico and Costa Rica.
AB  - Background: Some existing estimates suggest, controversially, that life
      expectancy at age 60 (LE60) of Latin American males is exceptionally high.
      Knowledge of adult mortality in Latin America is often based on unreliable
      statistics or indirect demographic methods. Objectives: This study aimed to
      gather direct estimates of mortality at older ages in two Latin American
      countries (Mexico and Costa Rica) using recent longitudinal surveys and to
      determine the socioeconomic status (SES) gradients for LE60. Methods: Data were
      collected from independent panels of approximately 7,000 older adults followed
      over more than a decade-the MHAS and CRELES surveys. The age-specific death rates
      were modeled with Gompertz regression, and thousands of life tables were
      simulated to estimate LE60 and its confidence interval. Results: LE60 estimates
      obtained from MHAS and CRELES are similar to those obtained from traditional
      statistics, confirming the exceptionally high LE60 of men in the two countries.
      The expected gradients of higher LE60 with higher SES are not present, especially
      among males, who even show reverse gradients (some exaggerated by data issues).
      Conclusions: Vital statistics correctly estimate elderly mortality in Mexico and
      Costa Rica. The higher-than-expected LE60 among Latin American males in general,
      and particularly among low-SES individuals, seems to be real; their determinants
      should be thoroughly investigated. Contribution: This study shows with hard,
      reliable data, independent of traditional statistics, that elderly males in
      tropical Latin America enjoy an exceptionally high life expectancy and that SES
      gradients are absent or even reverse.

PMID- 29576743
TI  - Bisdemethoxycurcumin and Its Cyclized Pyrazole Analogue Differentially Disrupt
      Lipopolysaccharide Signalling in Human Monocyte-Derived Macrophages.
AB  - Several studies suggest that curcumin and related compounds possess antioxidant
      and anti-inflammatory properties including modulation of lipopolysaccharide- (LPS
      ) mediated signalling in macrophage cell models. We here investigated the effects
      of curcumin and the two structurally unrelated analogues GG6 and GG9 in primary
      human blood-derived macrophages as well as the signalling pathways involved.
      Macrophages differentiated from peripheral blood monocytes for 7 days were
      activated with LPS or selective Toll-like receptor agonists for 24 h. The effects
      of test compounds on cytokine production and immunophenotypes evaluated as
      CD80+/CCR2+ and CD206+/CD163+ subsets were examined by ELISA and flow cytometry.
      Signalling pathways were probed by Western blot. Curcumin (2.5-10 MUM) failed to
      suppress LPS-induced inflammatory responses. While GG6 reduced LPS-induced
      IkappaB-alpha degradation and showed a trend towards reduced interleukin-1beta
      release, GG9 prevented the increase in proinflammatory CD80+ macrophage subset,
      downregulation of the anti-inflammatory CD206+/CD163+ subset, increase in p38
      phosphorylation, and increase in cell-bound and secreted interleukin-1beta
      stimulated by LPS, at least in part through signalling pathways not involving
      Toll-like receptor 4 and nuclear factor-kappaB. Thus, the curcumin analogue GG9
      attenuated the LPS-induced inflammatory response in human blood-derived
      macrophages and may therefore represent an attractive chemical template for
      macrophage pharmacological targeting.

PMID- 29576744
TI  - Critical Role of HAX-1 in Promoting Avian Influenza Virus Replication in Lung
      Epithelial Cells.
AB  - The PB1-F2 protein of influenza A virus has been considered a virulence factor,
      but its function in inducing apoptosis may be of disadvantage to viral
      replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown.
      We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that
      the mutant virus replicated less efficiently in human lung epithelial cells. The
      PB1-F2-deficient virus produced less apoptotic cells, indicating that PB1-F2 of
      the H9N2 virus promotes apoptosis, occurring at the early stage of infection, in
      the lung epithelial cells. To understand how host cells regulate PB1-F2-induced
      apoptosis, we explored to identify cellular proteins interacting with PB1-F2 and
      found that HCLS1-associated protein X-1 (HAX-1), located mainly in the
      mitochondria as an apoptotic inhibitor, interacted with PB1-F2. Increased
      procaspase-9 activations, induced by PB1-F2, could be suppressed by HAX-1. In HAX
      1 knockdown A549 cells, the replication of AIV H9N2 was suppressed in parallel to
      the activation of caspase-3 activation, which increased at the early stage of
      infection. We hypothesize that HAX-1 promotes AIV replication by interacting with
      PB1-F2, resulting in the suppression of apoptosis, prolonged cell survival, and
      enhancement of viral replication. Our data suggest that HAX-1 may be a promoting
      factor for AIV H9N2 replication through desensitizing PB1-F2 from its apoptotic
      induction in human lung epithelial cells.

PMID- 29576745
TI  - Anti-Inflamm-Ageing and/or Anti-Age-Related Disease Emerging Treatments: A
      Historical Alchemy or Revolutionary Effective Procedures?
AB  - The "long-life elixir" has long represented for humans a dream, a vanity's sin
      for remaining young and to long survive. Today, because of ageing population
      phenomenon, the research of antiageing interventions appears to be more important
      than ever, for preserving health in old age and retarding/or delaying the onset
      of age-related diseases. A hope is given by experimental data, which evidence the
      possibility of retarding ageing in animal models. In addition, it has been also
      demonstrated in animal life-extending studies not only the possibility of
      increasing longevity but also the ability to retard the onset of age-related
      diseases. Interestingly, this recent evidence is leading to promise of obtaining
      the same effects in humans and resulting in benefits for their health in old
      ages. In order to achieve this goal, different approaches have been used ranging
      from pharmacological targeting of ageing, basic biological assays, and big data
      analysis to the recent use of young blood, stem cells, cellular, genetic, and
      epigenetic reprogramming, or other techniques of regenerative medicine. However,
      only a little fraction of these approaches has the features for being tested in
      clinical applications. Here, new emerging molecules, drugs, and procedures will
      be described, by evidencing potential benefits and limitations.

PMID- 29576746
TI  - Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid
      Arthritis.
AB  - Cardiovascular disease is the main cause of morbidity and mortality in rheumatoid
      arthritis (RA). Despite the advent on new drugs targeting the articular
      manifestations, the burden of cardiovascular disease is still an unmet need in
      the management of RA. The pathophysiology of accelerated atherosclerosis
      associated to RA is not yet fully understood, and reliable and specific markers
      of early cardiovascular involvement are still lacking. Asymmetric
      dimethylarginine is gaining attention for its implication in the pathogenesis of
      endothelial dysfunction and as biomarkers of subclinical atherosclerosis.
      Moreover, the metabolic pathway of methylarginines offers possible targets for
      therapeutic interventions to decrease the cardiovascular risk. The purpose of
      this review is to describe the main causes of increased methylarginine levels in
      RA, their implication in accelerated atherosclerosis, the possible role as
      biomarkers of cardiovascular risk, and finally the available data on current
      pharmacological treatment.

PMID- 29576749
TI  - Arterial ageing: from the shadows to centre stage in cardiovascular medicine.

PMID- 29576747
TI  - CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms.
AB  - Asthma is an inflammatory disease in which proinflammatory cytokines have a role
      in inducing abnormalities of airway smooth muscle function and in the development
      of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+)
      signaling and contractility of airway smooth muscle, which results in nonspecific
      airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory
      mechanisms in airway smooth muscle and changes in these regulatory mechanisms
      encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+
      regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38
      cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced
      Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced
      cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human
      pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is
      focused on investigations on the role of CD38-cyclic ADP-ribose signaling in
      airway smooth muscle in the context of transcriptional and posttranscriptional
      regulation of CD38 expression. The specific roles of transcription factors NF-kB
      and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR
      140-3p and miR-708 in the posttranscriptional regulation and the underlying
      mechanisms of such regulation are discussed.

PMID- 29576750
TI  - Infant-Mother and Infant-Caregiver Emotional Relationships: Process Analyses of
      Interactions in Three Contemporary Childcare Arrangements.
AB  - Emotional relationships in infant-mother dyads in families where mothers provided
      full-time (MC) childcare were compared with those of families where mothers used
      in-home childcare (IHC) providers and family childcare (FCC) providers (N = 245).
      Infant relationships with childcare providers were also studied. Emotional
      relationships were adequate in all 3 childcare arrangements, but infant-mother
      dyads in IHC arrangements displayed healthier emotional relationships than infant
      mother dyads in MC arrangements; no differences in the health of emotional
      relationships with infants emerged among the three types of childcare providers
      (MC, IHC, FCC). Infant-mother dyads in IHC arrangements also displayed healthier
      emotional relationships than infant-IHC caregiver dyads, but infant-mother and
      infant-caregiver dyads were comparable in FCC families. Emotional relationships
      in infant-mother and infant-caregiver dyads were not correlated, regardless of
      the type of childcare.

PMID- 29576748
TI  - The Role of Toll-Like Receptor Signaling in the Progression of Heart Failure.
AB  - Medical systems worldwide are being faced with a growing need to understand
      mechanisms behind the pathogenesis of heart failure (HF) that is considered as a
      leading cause of morbidity and mortality around the world. Elevated levels of
      inflammatory mediators have been identified in patients with HF, which are
      primarily manifestations of innate immune responses mediated by pattern
      recognition receptors (PRRs). Toll-like receptors (TLRs), which belong to PRRs,
      are subjected to the release of pathogen-associated molecular patterns (PAMPs)
      and damage-associated molecular patterns (DAMPs) to generate innate immune
      responses. More and more emerging data indicate that TLR signaling pathway
      molecules are involved in the progression of HF. Herein, we present new data with
      regard to the activation of TLRs in the failing heart, focusing on TLR2, TLR3,
      TLR4, and TLR9, and suggest the potential use of TLRs in target therapy.

PMID- 29576751
TI  - Mother-Toddler Cortisol Synchrony Moderates Risk of Early Internalizing Symptoms.
AB  - Cortisol synchrony is the degree to which mother-toddler cortisol levels are
      mutually regulated within a dyad. Synchrony's impact on toddler development is
      not well understood, so this study investigated how synchronous cortisol levels
      (reactivity and total concentration) in mother-toddler dyads moderates the
      association between risk factors (i.e., maternal worry, toddler inhibition) and
      early internalizing symptoms. Seventy mothers and their 2-year-old toddlers
      provided interpretable saliva samples. Behavioral observations were made to
      assess the toddler's temperament at age 2, and mothers reported on their
      toddler's internalizing symptoms when toddlers were 2- and 3-years-old. Results
      suggest that mother-toddler synchrony in total cortisol concentration moderates
      the relation between risk factors and internalizing symptoms. Specifically,
      toddler inhibition and maternal worry were less associated with concurrent
      toddler internalizing symptoms when dyads demonstrated greater cortisol synchrony
      in total concentration. Further, synchrony in total cortisol levels marginally
      moderated the association between toddler inhibition and future internalizing
      symptoms, such that inhibited toddlers were less likely to demonstrate
      internalizing symptoms at age 3 when dyads demonstrated more cortisol synchrony.
      This suggests that cortisol synchrony may serve as an advantageous context that
      reduces the risk of developing of internalizing symptoms and augments the field's
      understanding of the implications of shared physiological responses within mother
      toddler dyads.

PMID- 29576752
TI  - Nutrient and Antinutrient Compositions and Heavy Metal Uptake and Accumulation in
      S. nigrum Cultivated on Different Soil Types.
AB  - Solanum nigrum cultivated on different soil texture types, sandy clay loam, silty
      clay loam, clay loam, loam, and control soils, were evaluated for proximate
      compositions, antinutrients, vitamins, and mineral composition with plant age
      using standard analytical methods. Accumulation of trace elements using
      translocation factor was studied to determine their toxic levels in plant
      tissues. Data were analysed by ANOVA and results expressed as means and standard
      deviation. Ash content, crude fibre, protein, alkaloid, phytate, and saponin
      ranged between 11.4 and 12%, 19.24 and 19.95%, 34.23 and 38.98, 42.08 and 45.76
      mg/ml, 0.84 and 1.17%, and 94.10 and 97.00%, respectively. Vitamins A, C, and B
      were present in high quantity. Macro- and micronutrients recorded showed that S.
      nigrum is a potential reservoir of minerals. Accumulation of micronutrients was
      observed to be the highest at the flowering stage between the 4th and 5th weeks
      after transplanting. Plants cultivated on clay loam, silty clay loam, and loam
      soils accumulated elevated nutritional compositions and abundant antinutrients.
      However, the accumulated trace metals in the plants are within the recommended
      safe levels. All nutrient values are in the recommended requirements for daily
      consumption.

PMID- 29576753
TI  - Autoimmune Retinopathy: Current Concepts and Practices (An American
      Ophthalmological Society Thesis).
AB  - Purpose: To elicit and evaluate opinions in the diagnosis and management of
      nonparaneoplastic autoimmune retinopathy (npAIR) among members of the American
      Uveitis Society (AUS) and to further the development of consensus and criteria in
      the diagnosis and management of npAIR. We hypothesize that despite lack of any
      clear guidelines, a general consensus in the clinical diagnosis and treatment of
      npAIR exists among uveitis experts. Methods: A literature review was performed
      and a panel of uveitis experts was consulted to formulate a survey regarding the
      diagnosis and management of npAIR. An online survey of 10 questions was
      developed, and a link was distributed through the AUS membership discussion list.
      We defined "general consensus" as meaning that a majority (>50%) of the
      respondents provided the same answer to a question. Results: Fifty-four members
      of the AUS responded to the survey. Thirty-eight members (70.4%) see one to three
      AIR patients per year. Greater than 50% consensus was reached on most items,
      particularly items relating to diagnostic features and tests (up to 96%
      consensus). Conclusions: The diagnosis and management of npAIR is challenging, as
      standardized clinical and laboratory diagnostic criteria have yet to be
      established. The results of this study support the presence of consensus
      regarding certain aspects of npAIR, but also indicate the need for developing
      clear clinical diagnostic criteria and treatment guidelines.

PMID- 29576754
TI  - 250 MHz passive Q-modulator for reflection resonators.
AB  - A simple scheme for dynamically switching the quality factor, Q, of a Loop-Gap
      Resonator (LGR); working at 250 MHz is presented. The addition of this Q
      modulator resulted in 30% improvement in Electron Paramagnetic Resonance imager
      signal-to-noise ratio. During pulse excitation, this scheme lowered the Q, while
      higher Q was obtained during signal detection. These conditions favored the image
      acquisition. The Q-modulator is passive; the transition between different states
      was actuated by the radio frequency power itself.

PMID- 29576755
TI  - Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer.
AB  - Purpose of Review: Pathological complete response is seen in approximately one
      fifth of rectal cancer patients following neoadjuvant chemoradiation. Since these
      patients have excellent oncological outcomes, there has been a rapidly growing
      interest in organ preservation for those who develop a clinical complete
      response. We review the watch-and-wait strategy and focus on all aspects of this
      hot topic, including who should be considered for this approach, how should we
      identify treatment response and what are the expected outcomes. Recent Findings:
      The major challenges in interpreting the data on watch-and-wait are the
      significant heterogeneity of patients selected for this approach and of methods
      employed to identify them. The evidence available comes mostly from retrospective
      cohort studies, but has shown good oncological outcomes, including the rate of
      successful salvage surgery, locoregional control and overall survival. Summary:
      There is currently not enough and not robust enough evidence to support watch-and
      wait as a standard approach, outside a clinical trial, for patients achieving
      clinical complete response following neoadjuvant chemoradiation. Furthermore,
      there is a lack of data on long-term outcomes. However, the results we have so
      far are promising, and there is therefore an urgent need for randomised control
      studies such as the TRIGGER trial to confirm the safety of this strategy.

PMID- 29576756
TI  - The importance of thermodynamics for molecular systems, and the importance of
      molecular systems for thermodynamics.
AB  - Improved understanding of molecular systems has only emphasised the
      sophistication of networks within the cell. Simultaneously, the advance of
      nucleic acid nanotechnology, a platform within which reactions can be exquisitely
      controlled, has made the development of artificial architectures and devices
      possible. Vital to this progress has been a solid foundation in the
      thermodynamics of molecular systems. In this pedagogical review and perspective,
      we discuss how thermodynamics determines both the overall potential of molecular
      networks, and the minute details of design. We then argue that, in turn, the need
      to understand molecular systems is helping to drive the development of theories
      of thermodynamics at the microscopic scale.

PMID- 29576757
TI  - Chemical reaction network designs for asynchronous logic circuits.
AB  - Chemical reaction networks (CRNs) are a versatile language for describing the
      dynamical behaviour of chemical kinetics, capable of modelling a variety of
      digital and analogue processes. While CRN designs for synchronous sequential
      logic circuits have been proposed and their implementation in DNA demonstrated, a
      physical realisation of these devices is difficult because of their reliance on a
      clock. Asynchronous sequential logic, on the other hand, does not require a
      clock, and instead relies on handshaking protocols to ensure the temporal
      ordering of different phases of the computation. This paper provides novel CRN
      designs for the construction of asynchronous logic, arithmetic and control flow
      elements based on a bi-molecular reaction motif with catalytic reactions and
      uniform reaction rates. We model and validate the designs for the deterministic
      and stochastic semantics using Microsoft's GEC tool and the probabilistic model
      checker PRISM, demonstrating their ability to emulate the function of
      asynchronous components under low molecular count.

PMID- 29576758
TI  - Programming discrete distributions with chemical reaction networks.
AB  - We explore the range of probabilistic behaviours that can be engineered with
      Chemical Reaction Networks (CRNs). We give methods to "program" CRNs so that
      their steady state is chosen from some desired target distribution that has
      finite support in [Formula: see text], with [Formula: see text]. Moreover, any
      distribution with countable infinite support can be approximated with arbitrarily
      small error under the [Formula: see text] norm. We also give optimized schemes
      for special distributions, including the uniform distribution. Finally, we
      formulate a calculus to compute on distributions that is complete for finite
      support distributions, and can be compiled to a restricted class of CRNs that at
      steady state realize those distributions.

PMID- 29576759
TI  - Petri-net-based 2D design of DNA walker circuits.
AB  - We consider localised DNA computation, where a DNA strand walks along a binary
      decision graph to compute a binary function. One of the challenges for the design
      of reliable walker circuits consists in leakage transitions, which occur when a
      walker jumps into another branch of the decision graph. We automatically identify
      leakage transitions, which allows for a detailed qualitative and quantitative
      assessment of circuit designs, design comparison, and design optimisation. The
      ability to identify leakage transitions is an important step in the process of
      optimising DNA circuit layouts where the aim is to minimise the computational
      error inherent in a circuit while minimising the area of the circuit. Our 2D
      modelling approach of DNA walker circuits relies on coloured stochastic Petri
      nets which enable functionality, topology and dimensionality all to be integrated
      in one two-dimensional model. Our modelling and analysis approach can be easily
      extended to 3-dimensional walker systems.

PMID- 29576760
TI  - KniMet: a pipeline for the processing of chromatography-mass spectrometry
      metabolomics data.
AB  - Introduction: Data processing is one of the biggest problems in metabolomics,
      given the high number of samples analyzed and the need of multiple software
      packages for each step of the processing workflow. Objectives: Merge in the same
      platform the steps required for metabolomics data processing. Methods: KniMet is
      a workflow for the processing of mass spectrometry-metabolomics data based on the
      KNIME Analytics platform. Results: The approach includes key steps to follow in
      metabolomics data processing: feature filtering, missing value imputation,
      normalization, batch correction and annotation. Conclusion: KniMet provides the
      user with a local, modular and customizable workflow for the processing of both
      GC-MS and LC-MS open profiling data.

PMID- 29576761
TI  - Surgical outcomes of laparoscopic hysterectomy with concomitant endometriosis
      without bowel or bladder dissection: a cohort analysis to define a case-mix
      variable.
AB  - Background: Pelvic endometriosis is often mentioned as one of the variables
      influencing surgical outcomes of laparoscopic hysterectomy (LH). However, its
      additional surgical risks have not been well established. The aim of this study
      was to analyze to what extent concomitant endometriosis influences surgical
      outcomes of LH and to determine if it should be considered as case-mix variable.
      Results: A total of 2655 LH's were analyzed, of which 397 (15.0%) with
      concomitant endometriosis. For blood loss and operative time, no measurable
      association was found for stages I (n = 106) and II (n = 103) endometriosis
      compared to LH without endometriosis. LH with stages III (n = 93) and IV (n = 95)
      endometriosis were associated with more intra-operative blood loss (p = < .001)
      and a prolonged operative time (p = < .001) compared to LH without endometriosis.
      No significant association was found between endometriosis (all stages) and
      complications (p = .62). Conclusions: The findings of our study have provided
      numeric support for the influence of concomitant endometriosis on surgical
      outcomes of LH, without bowel or bladder dissection. Only stages III and IV were
      associated with a longer operative time and more blood loss and should thus be
      considered as case-mix variables in future quality measurement tools.

PMID- 29576762
TI  - A bioclimatic characterization of high elevation habitats in the Alborz mountains
      of Iran.
AB  - The Alborz mountains in N-Iran at 36 degrees  N rise from the Caspian Sea to 5671
      m a.s.l., with warm-temperate, winter-deciduous forests in the lower montane belt
      in northern slopes, and vast treeless terrain at higher elevation. A lack of
      rainfall (ca. 550 mm at high elevations) cannot explain the absence of trees.
      Hence, it is an open question, which parts of these mountains belong to the
      alpine belt. Here we use bioclimatic data to estimate the position of the
      potential climatic treeline, and thus, define bioclimatologically, what is alpine
      and what is not. We employed the same miniature data loggers and protocol that
      had been applied in a Europe-wide assessment of alpine climates and a global
      survey of treeline temperatures. The data suggest a potential treeline position
      at ca. 3300 m a.s.l., that is ca. 900 m above the upper edge of the current oak
      forest, or 450 m above its highest outposts. The alpine terrain above the
      climatic treeline position shows a temperature regime comparable to sites in the
      European Alps. At the upper limit of angiosperm life, at 4850 m a.s.l., the
      growing season lasted 63 days with a seasonal mean root zone temperature of 4.5 
      degrees C. We conclude that (1) the absence of trees below 2850 m a.s.l. is
      clearly due to millennia of land use. The absence of trees between 2850 and 3300
      m a.s.l. is either due to the absence of suitable tree taxa, or the only
      potential regional taxon for those elevations, Juniperus excelsa, had been
      eradicated by land use as well. (2) These continental mountains provide thermal
      life conditions in the alpine belt similar to other temperate mountains. (3)
      Topography and snow melt regimes play a significant role for the structure of the
      alpine vegetation mosaics.

PMID- 29576763
TI  - Corrigendum: Genome Data Provides High Support for Generic Boundaries in
      Burkholderia Sensu Lato.
AB  - [This corrects the article on p. 1154 in vol. 8, PMID: 28694797.].

PMID- 29576764
TI  - Corrigendum: Specific Antibody Deficiency: Controversies in Diagnosis and
      Management.
AB  - [This corrects the article on p. 586 in vol. 8, PMID: 28588580.].

PMID- 29576765
TI  - Extensions of the natural approach to refinements and generalizations of some
      trigonometric inequalities.
AB  - In this paper we propose a new method for sharpening and refinements of some
      trigonometric inequalities. We apply these ideas to some inequalities of Wilker
      Cusa-Huygens type.

PMID- 29576766
TI  - Use of NSAIDs via the Rectal Route for the Prevention of Pancreatitis after ERCP
      in All-Risk Patients: An Updated Meta-Analysis.
AB  - The aim of this study was to assess the efficacy of the rectal administration of
      nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-ERCP
      pancreatitis (PEP). We searched database for randomized controlled trials (RCTs)
      comparing periprocedural rectal administration of NSAIDs with placebo for the
      prevention of PEP. The rectal administration of NSAIDs significantly decreased
      the incidence of PEP in the whole patient population (odds ratio (OR): 0.44, 95%
      confidence interval (CI): 0.30-0.64, P < 0.0001), high-risk patients (OR: 0.34,
      95% CI: 0.19-0.58, P = 0.0001), and all-risk patients (OR: 0.51, 95% CI: 0.31
      0.84, P = 0.008). The incidence of PEP was reduced by indomethacin (OR: 0.54, 95%
      CI: 0.36-0.82, P = 0.004) and diclofenac (OR: 0.27, 95% CI: 0.15-0.46, P <
      0.00001). The administration of NSAIDs before (OR: 0.42, 95% CI: 0.25-0.73, P =
      0.002) or after (OR: 0.39, 95% CI: 0.27-0.56, P < 0.00001) ERCP reduced PEP. The
      NSAIDs were associated with a reduction in mild PEP (OR: 0.55, 95% CI: 0.36-0.83,
      P = 0.004) and moderate-to-severe PEP (OR: 0.47, 95% CI: 0.28-0.79, P = 0.004).
      The rectal administration of NSAIDs reduced the incidence of PEP in high-risk and
      all-risk patients.

PMID- 29576767
TI  - Comparison of Concomitant Mesalamine and Immunomodulator Therapy and
      Immunomodulator Monotherapy for Crohn's Disease.
AB  - Background: Although immunomodulators are increasingly used in Crohn's disease
      (CD), a significant number of gastroenterologists still use 5-aminosalicylate (5
      ASA) in combination with azathioprine (AZA) or 6-mercaptopurine (6-MP); there is
      limited evidence regarding the benefit of concomitant 5-ASA with AZA/6-MP
      compared with AZA/6-MP monotherapy for the treatment of CD. Study Design: A total
      of 106 patients who received AZA/6-MP for more than 3 months between January 1991
      and May 2014 were identified retrospectively. Each patient was matched with 3
      randomly selected controls who were treated with concomitant therapy during the
      same period. Results: The cumulative probabilities of steroid use at 5 and 10
      years were 24.9% and 75.8% in the 5-ASA + AZA/6-MP group and 31.2% and 87.8% in
      the AZA/6-MP group, respectively (P = 0.187). The cumulative probabilities of
      anti-TNF use, resectional surgery, and disease-related hospitalization were
      comparable between the groups. The younger age and the use of lower doses of
      immunomodulators were associated with higher requirement of rescue therapy.
      Conclusions: This study did not demonstrate that the concomitant use of 5-ASA
      with AZA/6-MP showed the proof or effect in terms of steroid requirements, anti
      TNF use, resectional surgery, or disease-related hospitalization compared with
      that of AZA/6-MP alone.

PMID- 29576769
TI  - Favorable Effect of Anti-TNF Therapy on Insulin Sensitivity in Nonobese,
      Nondiabetic Patients with Inflammatory Bowel Disease.
AB  - Background: The aim of this study was to investigate the effect of anti-TNF
      therapy on glucose and lipid metabolism in nondiabetic, nonobese patients with
      inflammatory bowel disease (IBD). Patients and Methods: We studied 44 patients
      with IBD, without a known history of diabetes. Three of the patients were
      diagnosed with overt diabetes and were excluded. Eighteen of the remaining
      patients (9 M/9 F, 33.6 +/- 8.8 years) were on anti-TNF therapy for longer than 1
      year, while 23 patients (16 M/7 F, 38.7 +/- 12.5 years) were treated with
      aminosalicylates (AMSs). Twelve of the patients from the second group were then
      treated with anti-TNF and reassessed 6 months later. Fasting glucose, insulin, c
      peptide, HbA1c, lipid, CRP, and fibrinogen levels were determined, and HOMA-IR
      index was calculated in all patients. Results: Patients from the two therapy
      groups were matched for age and BMI and were not obese. We did not find any
      differences between patients from the two therapy groups regarding fasting
      glucose, c-peptide, HbA1c, total cholesterol, HDL, LDL, triglycerides, CRP, and
      HOMA-IR index. In patients who were treated for 6 months with anti-TNF, a
      statistically significant decrease in insulin (before 15.5 +/- 5.9 versus after
      9.9 +/- 2.9 MUIU/ml, p = 0.042) and c-peptide (before 2.4 +/- 1 versus after 1.3
      +/- 0.4 ng/ml, p = 0.030) levels as well as the HOMA-IR index (before 4.2 +/- 1.9
      versus after 2.2 +/- 0.9, p = 0.045) was observed, without any changes in weight,
      BMI, glucose, HbA1c, lipid, CRP, and fibrinogen levels. Conclusion: Anti-TNF
      therapy exerts a favorable effect on insulin sensitivity, while it has no effect
      on lipid levels in nondiabetic, nonobese patients with inflammatory bowel
      disease.

PMID- 29576768
TI  - Effect of Endotoxemia in Suckling Rats on Pancreatic Integrity and Exocrine
      Function in Adults: A Review Report.
AB  - Background. Endotoxin (LPS), the component of Gram-negative bacteria, is
      responsible for sepsis and neonatal mortality, but low concentrations of LPS
      produced tissue protection in experimental studies. The effects of LPS applied to
      the suckling rats on the pancreas of adult animals have not been previously
      explored. We present the impact of neonatal endotoxemia on the pancreatic
      exocrine function and on the acute pancreatitis which has been investigated in
      the adult animals. Endotoxemia was induced in suckling rats by intraperitoneal
      application of LPS from Escherichia coli or Salmonella typhi. In the adult rats,
      pretreated in the early period of life with LPS, histological manifestations of
      acute pancreatitis have been reduced. Pancreatic weight and plasma lipase
      activity were decreased, and SOD concentration was reversed and accompanied by a
      significant reduction of lipid peroxidation products (MDA + 4 HNE) in the
      pancreatic tissue. In the pancreatic acini, the significant increases in protein
      signals for toll-like receptor 4 and for heat shock protein 60 were found. Signal
      for the CCK1 receptor was reduced and pancreatic secretory responses to caerulein
      were diminished, whereas basal enzyme secretion was unaffected. These pioneer
      studies have shown that exposition of suckling rats to endotoxin has an impact on
      the pancreas in the adult organism.

PMID- 29576770
TI  - The cold ceramic material.
AB  - The purpose of this paper was to review the composition, sealing ability,
      biocompatibility and various physical properties of cold ceramic (CC) material
      that potentially used as a root filling material. The review of the articles was
      performed by electronic and manual searching methods regarding the properties of
      CC from November 2000 to May 2016. The results revealed that there were many
      published reports carried out on the properties of CC. Only one article had
      extensively studied the composition of CC, five studies had investigated the
      sealing ability of CC, three articles had studied the biocompatibility, and some
      studies had investigated the radiopacity, setting time, pH value, and solubility
      of CC. It was concluded that CC material had good potential for endodontic use.
      Furthermore, clinical studies are needed in these areas.

PMID- 29576771
TI  - Effects of artifact removal on cone-beam computed tomography images.
AB  - Background: Dental implants and metal fillings may cause artifacts in cone-beam
      computed tomography (CBCT) images and reduce image quality and anatomic accuracy.
      The purposes of this study are a subjective evaluation of anatomic landmarks and
      linear bone measurements after applying artifact removal (low-medium) option on
      CBCT images. Materials and Methods: In this cross-sectional study, thirty CBCT
      images from thirty qualified patients were selected in a private radiology
      center. Low and medium artifact removal was applied to images. Three radiologists
      assessed the visibility of the mandibular canal, mental foramen, and lamina dura
      in images. Crestal width and bone length were also measured in three groups of
      images and was compared by exact McNemar test. ICC test (two-way random model,
      absolute agreement types) was calculated for comparison of linear bone
      measurements in three images groups. P <= 0.05 was considered statistically
      significant. Results: Percent agreement of determining mental foramen (outline
      and location), mandibular canal (outline and location), and lamina dura between
      three groups of images were 100%, 100%, 83.3%, 96.7%, and 56.6%, respectively.
      The results of exact McNemar test revealed that medium artifact removal group had
      a statistical difference in lamina dura observation with none and low artifact
      removal groups (P < 0.001). Intraclass correlation coefficient showed no
      statistical differences in crestal width and bone length between groups (P <
      0.001). Conclusion: Applying artifact removal does not affect the visibility of
      large anatomical structures and linear bone measurements, but delicate structures
      such as lamina dura may become less clear after artifact removal.

PMID- 29576772
TI  - Effectiveness of MI Paste Plus and Remin Pro on remineralization and color
      improvement of postorthodontic white spot lesions.
AB  - Background: This clinical trial investigated the effectiveness of two
      remineralizing creams on regression of white spot lesions (WSLs) after
      orthodontic therapy. Materials and Methods: The study included patients with WSLs
      on their upper anterior teeth who recently completed orthodontic treatment at the
      Department of Orthodontics of Mashhad Dental School and two private offices. The
      participants were randomly assigned into three groups by treatment: (1) a 12-week
      regimen of a cream containing casein phosphopeptide-amorphous calcium phosphate
      and fluoride (MI Paste Plus); (2) a 12-week regimen of a cream containing
      hydroxyapatite and fluoride (Remin Pro); and (3) usual home care (control).
      Thirty-nine patients participated and three withdrew. The main outcomes including
      area, mineral content, and color of WSLs were measured at enrolment and 4, 8, and
      12 weeks later, respectively. Blinding was applied for outcome assessment only.
      The data were analyzed by analysis of variance and repeated measures analysis at
      the statistical significance of P < 0.05. Results: Over a 3-month period, the
      application of both MI Paste Plus and Remin Pro caused significantly greater
      reduction in area and significantly higher increase in mineral content of WSLs
      compared to the control group (P < 0.05). The appearance of WSLs improved
      significantly in both experimental groups (P < 0.05), but not in the control
      group. No side effect was observed throughout the experiment. Conclusion: The
      application of either MI Paste Plus or Remin Pro was effective in reducing the
      area, increasing the mineral content and improving the appearance of
      demineralized enamel, indicating that these products could be recommended for
      managing postorthodontic WSLs.

PMID- 29576773
TI  - Visfatin expression in gingival tissues of chronic periodontitis and aggressive
      periodontitis patients: An immunohistochemical analysis.
AB  - Background: Visfatin, also known as nicotinamide phosphoribosyltransferase, has
      been suggested as a pro-inflammatory and immunomodulating marker for
      periodontitis. The aim of this study was an immunohistochemical analysis of
      visfatin in gingival tissues of patients with chronic periodontitis and
      aggressive periodontitis. Materials and Methods: In this cross-sectional study
      based on clinical evaluation and inclusion and exclusion criteria. Twenty
      patients with generalized chronic periodontitis, 13 patients with generalized
      aggressive periodontitis, and 20 periodontally healthy individuals enrolled.
      Gingival tissue samples were obtained during periodontal flap surgery and crown
      lengthening surgery in periodontal patients and healthy group, respectively.
      Tissue samples were transferred to a pathology laboratory to determine the degree
      of inflammatory infiltration by hematoxylin and eosin staining and the level of
      visfatin expression by immunohistochemistry. The data were analyzed using SPSS
      version 20 statistical software and paired t-test, Mann-Whitney test, and
      Spearman rank correlation coefficient. P < 0.05 was considered statistically
      significant. Results: Inflammation grading and visfatin expression were
      significantly higher in periodontally diseased gingiva compared to the control
      group (P < 0.05). However, no significant difference was found between two
      diseased groups. The relationship between inflammation grading and visfatin
      expression in aggressive periodontitis group was statistically significant,
      positive and relatively strong (P = 0.025, r = 0.617). However, no significant
      relationship has been found between visfatin expression and inflammation grading
      in the chronic periodontitits and control groups (P > 0.05). Conclusion: Visfatin
      expression was increased in gingival tissues of chronic periodontitis and
      aggressive periodontitis patients. Hence, visfatin may have a role in the
      etiopathogenesis of chronic periodontitis and aggressive periodontitis.

PMID- 29576774
TI  - Comparison of antimicrobial effect of Ziziphora tenuior, Dracocephalum moldavica,
      Ferula gummosa, and Prangos ferulacea essential oil with chlorhexidine on
      Enterococcus faecalis: An in vitro study.
AB  - Background: Different irrigating solutions with high antimicrobial activity have
      been introduced for cleaning of the root canal system. However, effects of
      Prangos ferulacea (PF), Ziziphora tenuior (ZT), Dracocephalum moldavica (DM), and
      Ferula gummosa (FG) on oral and dental pathogens have not been extensively
      evaluated due to their optimal biocompatibility and insignificant side effects.
      The aim of this study was to evaluate the antibacterial effects of essential oils
      of mentioned plants on Enterococcus faecalis. Materials and Methods: In this in
      vitro study the plants were collected from Zanjan Province, Iran. Analysis of the
      essential oil was carried out by gas chromatography/mass chromatography. Micro
      broth dilution and disc diffusion methods were used for assessment of the
      antimicrobial activity, and minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) were evaluated. Results: All the four essential
      oils had antibacterial effects on E. faecalis, and ZT had the greatest
      antibacterial activity. Assessment of the mean diameter of the growth inhibition
      zone showed higher antibacterial activity of PF and ZT than that of
      chlorhexidine. The MIC and MBC of ZT showed that the antimicrobial activity of ZT
      against E. faecalis was greater than that of other plants evaluated in this
      study. Conclusion: The results of this study indicated significant antibacterial
      effects of the mentioned plants on E. faecalis. The greatest antimicrobial
      activity belonged to ZT. The current study suggests extraction of effective
      compounds in these medicinal plants to use them in the clinical setting.

PMID- 29576775
TI  - A comparative evaluation of Morinda citrifolia, green tea polyphenols, and
      Triphala with 5% sodium hypochlorite as an endodontic irrigant against
      Enterococcus faecalis: An in vitro study.
AB  - Background: Endodontic infections require effective removal of microorganisms
      from the root canal system for long-term prognosis. Sodium hypochlorite (NaOCl)
      is the most effective irrigant currently, but potential complications due to its
      toxicity warrant search for newer alternatives. In this study, the antimicrobial
      efficacy of Morinda citrifolia (MC), green tea polyphenols and Triphala was
      compared with 5% NaOCl against Enterococcus faecalis. Materials and Methods: In
      this in vitro study sixty extracted human premolar teeth were infected with E.
      faecalis, a Group D Streptococci for 48 h. At the end of 48 h, the vital
      bacterial population was assessed by counting the number of colony-forming units
      (CFUs) on blood agar plate. Samples were divided into five groups; Group I
      (distilled water), Group II (NaOCl), Group III (MC), Group IV (Triphala), and
      Group V (green tea polyphenols). The samples were irrigated with individual test
      agents and CFUs were recorded. Kruskal-Wallis test was performed as the
      parametric test to compare different groups. Student's t-test was used to compare
      mean values between groups before and after treatment with test agents (P <
      0.001). Results: NaOCl was the most effective irrigant the elimination of E.
      faecalis reinforcing its role as the best irrigant available currently and a gold
      standard for comparison of the experimental groups. Its antibacterial effect was
      comparable to Triphala. Among the experimental groups, MC showed the minimum
      antibacterial effect. Conclusion: The use of herbal alternatives as a root canal
      irrigant might prove to be advantageous considering the several undesirable
      characteristics of NaOCl.

PMID- 29576776
TI  - Feasibility of micro-computed tomography to detect and classify proximal caries
      lesions in vitro.
AB  - Background: Micro-computed tomography (micro-CT) has been widely described as a
      nondestructive in vitro imaging method although its accuracy for caries detection
      is still unclear. The aim of this study was to investigate the feasibility of
      micro-CT to detect and classify proximal caries lesions in posterior teeth, using
      different protocols. Materials and Methods: In this in vitro study, crowns of 122
      human teeth were scanned with Skyscan 1174 (Bruker, Kontich, Belgium) using the
      full-scan mode (360 degrees ). Reconstruction of 900 basis images was performed
      using NRecon Software (Bruker, Kontich, Belgium) for the protocol 1 (full-scan
      mode 360 degrees ), and 450 basis images were used to reconstruct the protocol 2
      (half-scan mode 180 degrees ). Three observers analyzed the reconstructed images
      concerning the presence and depth of proximal caries lesions (244 surfaces). To
      determine the presence/absence and depth of caries lesions, histological
      examination was conducted as reference standard level of significance McNemar and
      McNemar-Bowker tests compared the methods studied and the gold standard (P <
      0.05). Results: The intra- and inter-observer agreement for both methods ranged
      from moderate to excellent. There was no difference between both micro-CT methods
      and histology for the presence of lesions (P > 0.05). However, both methods
      differed with the reference standard for depth (P < 0.05). The disagreement
      occurred mostly in cases of enamel lesions. The highest diagnostic values were
      found for 180 degrees  rotation. Micro-CT performed well in detecting caries
      lesions compared to histology, meanwhile the classification of their depth
      presented lower values. Scan mode did not influence the detection. Conclusion:
      Both protocols of micro-CT tested presented an overall satisfactory performance
      in detecting proximal caries lesions; however, for the depth classification, the
      method was not accurate.

PMID- 29576777
TI  - Evaluation of the wettability of a resin-based sealer in contact with some herbal
      irrigants.
AB  - Background: An ideal root canal irrigant should be able to enhance the
      wettability of sealer to dentin walls. The aim of this study was to survey the
      contact angle between AH 26 sealer and dentin surface irrigated by four herbal
      essential oils, compared with normal saline and 5.25% sodium hypochlorite
      (NaOCl). Materials and Methods: In this in vitro study, 60 longitudinal dentin
      slices were obtained from thirty extracted single-rooted human mandibular first
      premolars. After smear layer removal, the samples were divided into six groups of
      10 samples and irrigated for 1 min with the experimental solutions followed by
      distilled water: G1: Myrtus communis, G2: Cinnamomum zeylanicum, G3: Zataria
      multiflora (ZM), G4: Cuminum cyminum (CC), G5: normal saline, and G6: NaOCl
      5.25%. The contact angle between AH 26 and the samples was measured using Motic
      Images Plus 2.0 software. Data were analyzed statistically using one-way analysis
      of variance (P < 0.05 consider significant). Results: All the herbal irrigants,
      except CC, increased the contact angle of AH 26 sealer (P <= 0.05). The least
      value of contact angle was seen in the samples treated with CC, and the maximum
      value was observed in samples treated with ZM. 5.25% NaOCl showed a slightly
      increased contact angle compared to normal saline; however, it was not
      statistically significant (P > 0.05). Conclusion: Under the experimental
      condition of this study, CC was able to increase dentin wettability and therefore
      may be regarded as a promising irrigant after careful evaluation of other
      properties of this irrigant.

PMID- 29576778
TI  - Cytotoxicity assessment of polyhydroxybutyrate/chitosan/nano- bioglass nanofiber
      scaffolds by stem cells from human exfoliated deciduous teeth stem cells from
      dental pulp of exfoliated deciduous tooth.
AB  - Background: The aim of this study was to compare the cytotoxicity and the
      biocompatibility of three different nanofibers scaffolds after seeding of stem
      cells harvested from human deciduous dental pulp. Given the importance of
      scaffold and its features in tissue engineering, this study demonstrated the
      construction of polyhydroxybutyrate (PHB)/chitosan/nano-bioglass (nBG)
      nanocomposite scaffold using electrospinning method. Materials and Methods: This
      experimental study was conducted on normal exfoliated deciduous incisors obtained
      from 6-year-old to 11-year-old healthy children. The dental pulp was extracted
      from primary incisor teeth which are falling aseptically. After digesting the
      tissue with 4 mg/ml of type I collagenase, the cells were cultured in medium
      solution. Identification of stem cells from human exfoliated deciduous teeth was
      performed by flowcytometry using CD19, CD14, CD146, and CD90 markers. Then, 1 *
      104 stem cells were seeded on the scaffold with a diameter of 10 mm * 0.3 mm.
      Cell viability was evaluated on days 3, 5, and 7 through methyl thiazol
      tetrazolium techniques (P < 0.05) on different groups that they are groups
      included (1) PHB scaffold (G1), (2) PHB/chitosan scaffold (G2), (3) the optimal
      PHB/chitosan/nBG scaffold (G3), (4) mineral trioxide aggregate (MTA), and (5) the
      G3 + MTA scaffold (G3 + MTA). Data were analyzed with two-way ANOVA at
      significance level of P < 0.05. Results: The results indicated that the
      PHB/chitosan/nBG scaffold and PHB/chitosan/nBG scaffold + MTA groups showed
      significant difference compared with the PHB/chitosan scaffold and PHB scaffold
      groups on the 7th day (P < 0.05). Conclusion: Thus, it can be concluded that the
      scaffold with nBG nanoparticles is more biocompatible than the other scaffolds
      and can be considered as a suitable scaffold for growth and proliferation of stem
      cells.

PMID- 29576779
TI  - Effect of containing silica fume on cytotoxicity of white mineral trioxide
      aggregate.
AB  - Background: Mineral trioxide aggregate (MTA) has a high biocompatibility and its
      physical properties could be improved by adding the containing silica fume an
      amorphous silicon dioxide (condensed silica fume [CSF]). The aim of this study
      was to evaluate the cytotoxicity of MTA mixed with CSF on the viability of L929
      mouse fibroblast cell using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium
      bromide reduction assay (MTT assay). Materials and Methods: In this in vitro
      study white MTA was mixed with distilled water according to the manufacturer's
      instructions. Mixtures of White MTA with 10%, 15%, and 20% CSF by weight were
      prepared and mixed with distilled water. Cytotoxicity of mixtures was compared
      with MTT assay on L929 mouse fibroblast cell line after 24, 48, and 72 h.
      Differences in cytotoxicity were assessed by one-way analysis of variance
      (ANOVA). Results: Mean +/- SD of vital cell counts cultured in MTA, MTA + 10%
      CSF, MTA + 15% CSF, and MTA + 20% CSF were 98% +/- 6%, 97% +/- 6%, 94% +/- 4%,
      and 98% +/- 4%, respectively. One-way ANOVA did not reveal any statistically
      significant difference between the groups (P > 0.05). Conclusion: It may be
      concluded that addition of CSF to MTA may not influence its cytotoxicity.

PMID- 29576780
TI  - Chair time saving method for treatment of an impacted maxillary central incisor
      with 15-month follow-up.
AB  - Maxillary permanent incisors have a major role in facial esthetics. Impaction of
      them has great adverse effect on smile and causes serious concerns in patient and
      parents. Physical barriers (e.g., overretained primary teeth, supernumerary
      teeth, and pathologic lesions), space problems, developmental abnormalities,
      altered eruption sequence, trauma, palatal clefts, and genetics can act as
      etiologic factors. Currently, the conventional technique to treatment of impacted
      teeth consists of a combined orthodontic and surgical approach, to guide the
      impacted teeth in a constant position and surrounded by normal hard and soft
      tissues. Treatment is challenging because of some limitations such as patient's
      age, cooperation, anchorage, and mechanotherapy possibilities. Hence,
      sophisticated treatment planning is crucial. A 9-year-old girl with horizontally
      impacted maxillary left central incisor treated with surgical exposure and closed
      orthodontic forced eruption with 2 * 4 partial setup fixed appliances. Force was
      applied with 0.014 inch nickel-titanium wire as elastic overlay and handmade
      ligated bracket. To save chair time in each appointment, the overlay was
      activated by twisting of ligature wire extensions around it. After 16-month
      treatment, impacted incisor emerged in oral cavity, with accepted alignment and
      inclination. Handmade ligated bracket with ligature wire extensions is useful for
      the treatment of impacted teeth. Due to easy activation of overlay in this
      method, chair time become short in each appointment.

PMID- 29576781
TI  - The New Mayo Clinic Risk Score Characteristics in Acute Coronary Syndrome in
      Patients Following Percutaneous Coronary Intervention.
AB  - Background: Mortality and major adverse cardiac events (MACE) frequently occur
      after percutaneous coronary intervention (PCI). Therefore, the ability to predict
      such events through an established risk stratification method is of great
      importance. The present study was aimed at determining the risk stratification of
      mortality and MACE in post-PCI patients at the intensive cardiac care unit of
      Cipto Mangunkusumo Hospital (CMH) using 7 variables of the New Mayo Clinic Risk
      Score (NMCRS). Method: This cross-sectional study drew upon secondary data
      gathered from the medical records of 313 patients that underwent PCI at the
      intensive cardiac care unit (ICCU) of CMH between August 1st, 2013, and August
      31st, 2014. The primary end point was all-cause mortality and MACE. Seven
      variables in the NMCRS, namely age, left ventricular ejection fraction, serum
      creatinine, preprocedural cardiogenic shock, myocardial infarction, and
      peripheral arterial disease, were evaluated. Results: The mortality and MACE
      incidence rates in the post-PCI patients were 3.8% (95%CI: 2.6-5.0) and 8.3% (95%
      CI: 6.6-10.0), respectively. Regarding the NMCRS stratification, elderly patients
      with lower left ventricular ejection fraction, increased serum creatinine,
      preprocedural cardiogenic shock, myocardial infarction, and peripheral arterial
      disease had higher mortality and MACE incidence rates among the post-PCI
      patients. The mortality and MACE incidence rates significantly increased in the
      post-PCI patients with a higher NMCRS. Conclusion: Patients with a higher NMCRS
      had a tendency toward higher mortality and MACE incidence rates following PCI.

PMID- 29576782
TI  - Extent of Coronary Stenosis and Anxiety Symptoms among Patients Undergoing
      Coronary Angiography.
AB  - Background: The association between coronary angiographic findings and the level
      of anxiety symptoms among patients who undergo coronary angiography is not known.
      The aim of this study was to investigate the association between the extent of
      coronary stenosis and anxiety symptoms in patients who undergo coronary
      angiography. Methods: In a cross-sectional study, 106 patients who underwent
      coronary angiography and had varying degrees of coronary artery disease were
      enrolled. Demographic characteristics (i.e., age and gender), socioeconomic
      status (i.e., educational attainment, income, and marital status), and
      traditional risk factors (i.e., hypertension, diabetes mellitus, hyperlipidemia,
      and smoking) were measured. The independent variable was the extent of coronary
      stenosis shown by coronary angiography, coded as single-vessel disease (n = 19),
      2-vessel disease (n = 28), or 3-vessel disease (n = 59). The main outcome was
      symptoms of anxiety measured using the Hospital Anxiety Depression Scale (HADS).
      The Kruskal-Wallis test was used for bivariate analysis, and linear regression
      was applied for multivariable analysis. Results: Participants were mostly men (n
      = 78, 73%), at a mean age of 50.14 +/- 10.60 years. We found an inverse
      association between the extent of coronary stenosis and anxiety symptoms in our
      samples. Anxiety symptoms were lowest in the patients with 3-vessel disease and
      highest in those with single-vessel disease. The above association remained
      significant in a linear regression model, controlled for the demographic,
      socioeconomic, and traditional risk factors. Conclusion: An inverse association
      may exist between the extent of coronary stenosis and the severity of anxiety
      symptoms in patients who undergo coronary angiography. Patients who undergo
      angiography and have fewer angiographic findings require screening for anxiety
      symptoms.

PMID- 29576783
TI  - Nigerian Children with Acquired Heart Disease: The Experience in Lagos.
AB  - Background: Most of the recent reports on acquired heart diseases (AHDs) among
      Nigerian children are either retrospective or cover a short period of time with
      fewer subjects. The last report on AHDs among children in Lagos was about a
      decade ago; it was, however, not specific to children with AHDs but was part of a
      report on structural heart diseases among children in Lagos. The present study
      was carried out to document the prevalence and profile of different AHDs in
      children and to compare the findings with those previously reported. Methods: We
      conducted a quantitative, nonexperimental, prospective, and cross-sectional
      review of all consecutive cases of AHDs diagnosed with echocardiography at the
      Lagos State University Teaching Hospital between January 2007 and June 2016.
      Comparisons between the normally distributed quantitative data were made with the
      Student t test, while the chi2 test was applied for the categorical data.
      Results: The subjects with AHDs were 73 males and 52 females, with a male-to
      female ratio of 1.4:1. The children were aged 15 days to 14 years, with a mean of
      6.61 +/- 4.26 years. Rheumatic heart disease was the most common AHD, documented
      in a quarter of the children, followed by dilated cardiomyopathy and pericardial
      effusion in 20.8% and 17.3%, respectively. Less common lesions encountered were
      Kawasaki disease, mitral valve prolapse, hyperdynamic circulation, and
      supraventricular tachycardia. Conclusion: Rheumatic heart disease was still the
      most common AHD in the children in the present study. Dilated cardiomyopathy and
      pericardial effusion are on the increase as has been reported earlier.

PMID- 29576784
TI  - Congenital Aortico-Left Ventricular Tunnel: A Case Report of a Rare Cause of
      Aortic Regurgitation in Adults.
AB  - The aortico-left ventricular tunnel is a rare congenital abnormality resulting in
      a pathologic connection between the aorta and the left ventricle. It often
      presents during infancy or early childhood as a cardiac failure symptom or an
      incidental finding of a cardiac murmur due to severe aortic regurgitation. It is,
      however, also occasionally found in asymptomatic adults. We describe a 20-year
      old female presenting with palpitations in whom clinical evaluations with
      echocardiography and computed tomography angiography led to the diagnosis of
      severe aortic regurgitation caused by a tunnel connecting the right sinus of the
      aorta to the left ventricle. The patient underwent successful obstruction of the
      tunnel with an autologous pericardial patch and the repair of the dilated aortic
      root via the reduction aortoplasty technique. She was discharged on the 5th
      postoperative day with no complications. At 1 month's follow-up, she remained
      asymptomatic and echocardiography showed aortic valve competence with no residual
      regurgitation.

PMID- 29576785
TI  - Incidental Finding of a Large Mobile Aortic Arch Mass during Conventional
      Angiography.
AB  - Thromboembolism occurs commonly in general practice and leads to significant
      health burden. Apart from cardiac sources, aortic atherosclerotic plaques
      contribute considerably to thromboembolism. A 63-year-old diabetic hypertensive
      woman referred to our center due to exertional chest pain unresponsive to optimal
      medical therapy and underwent coronary angiography. Owing to resistance during
      guide-wire advancement, an aortography was performed. Aortic arch injection
      demonstrated a large suspended mass distal to the left subclavian artery with
      free movement in the descending thoracic aorta. Echocardiography revealed
      widespread atherosclerotic changes in the aortic arch with a large hypermobile
      mass. Dual-source multi-slice (2 * 128:256) computed tomography angiography of
      the whole aorta revealed a large floating mass (in favor of a thrombus) in the
      distal portion of the arch. The patient underwent coronary artery bypass grafting
      due to severe coronary artery disease. The intra-aortic mass, which was actually
      a large atherosclerotic plaque, was resected at the same session. She was
      discharged uneventfully and during a 1-year follow-up, she had no embolic events.

PMID- 29576786
TI  - Malignant Hyperthermia: Report of Two Cases with a Neglected Complication in
      Cardiac Surgery.
AB  - Malignant hyperthermia (MH) can develop after contact with volatile anesthetics
      (halothane, enflurane, isoflurane, sevoflurane, and desflurane) as well as
      succinylcholine and cause hypermetabolism during anesthesia, which is associated
      with high mortality when untreated. Early diagnosis and treatment could be life
      saving. During cardiac surgery, hypothermia and cardiopulmonary bypass make the
      diagnosis of MH extremely challenging compared with other settings such as
      general surgery. We herein report 2 cases of MH, graded as "very likely" or
      "almost certain" based on the MH clinical grading scale. A 14-month-old infant
      and a 53-year-old male underwent surgery for severe pulmonary valve stenosis and
      mitral valve replacement, respectively. Both of them were extubated on the
      operation day, but they deteriorated with the development of high-grade fever,
      hypotension, renal failure, and acidosis. The first case had muscle spasms.
      Unfortunately, the delayed symptoms of MH in the early postoperative course were
      not diagnosed in these 2 cases, which caused permanent neurologic damage in the
      first case and death in the second one. However, the infant was discharged from
      the hospital after 2 months.

PMID- 29576787
TI  - Management of Cardiovascular Disorders in Patients with Noonan Syndrome: A Case
      Report.
AB  - The Noonan syndrome is a rare disorder, one of whose major complications is
      cardiovascular involvement. A wide spectrum of congenital heart diseases has been
      observed in this syndrome. The most common cardiac disorder is pulmonary valve
      stenosis, which has a progressive nature. Hypertrophic cardiomyopathy is less
      common, but its morbidity and mortality rates are high. We herein introduce a 12
      year-old boy with the typical findings of the Noonan syndrome. His symptoms began
      from infancy, and there was a gradual exacerbation in his respiratory and cardiac
      manifestations with age. The cardiac involvement included right ventricular
      outflow tract and pulmonary valve stenosis, hypertrophic cardiomyopathy, and
      subaortic valve stenosis. Due to the progressive course of the disease, surgical
      repair was done. Although the patient had a difficult postoperative period, his
      general condition improved and he was discharged. At 3 months' follow-up, his
      symptoms showed improvement. Additionally, there was a reduction in the
      echocardiographic parameters of the outflow tract stenosis gradient as well as a
      significant improvement in the cardiac hemodynamic indices.

PMID- 29576788
TI  - Successful Treatment of a Catheter-Induced Superior Vena Cava Syndrome through
      Catheter-Directed Thrombolysis: A Case Report.
AB  - Superior vena cava (SVC) syndrome is a medical condition resulting from the
      obstruction of the blood flow through the large central veins. Recently, central
      venous catheters have been reported as the increasingly common cause of this
      syndrome. We describe a 56-year-old woman with previous history of metastatic
      colon cancer, who had recently undergone central venous catheter insertion for
      her second chemotherapy course. Eight days following port insertion, she
      presented with signs and symptoms suggestive of acute SVC syndrome, which was
      successfully managed with catheter-directed thrombolysis. The pre-discharge
      transesophageal echocardiography and conventional angiography showed a patent
      SVC. The patient was discharged and remained asymptomatic over a 6-month follow
      up. This case shows that catheter-directed thrombolysis may be used as a safe
      treatment for catheter-induced acute SVC syndrome in patients who have undergone
      catheter insertion in the central vein.

PMID- 29576789
TI  - Hydatid Cyst Mimicking a Pericardial Cyst.

PMID- 29576790
TI  - A New Technique of Heterotopic Heart Transplantation with Direct Pulmonary Artery
      Anastomosis.

PMID- 29576791
TI  - A Systematic Review about the Efficacy and Safety of Tripterygium wilfordii
      Hook.f. Preparations Used for the Management of Rheumatoid Arthritis.
AB  - Tripterygium wilfordii Hook.f. (TWHF) is a traditional Chinese herb long used for
      rheumatoid arthritis (RA) treatment, in modern times, often in the form of
      various Tripterygium wilfordii Hook.f. preparations (TWPs). This systematic
      review and meta-analysis focuses on analyzing the clinical efficacy and safety of
      TWPs in the treatment of RA. Databases were searched to collect the randomized
      controlled trials (RCTs) on TWPs treating RA published on or before April 10,
      2017. Data from 11 studies were included in this meta-analysis. Compared with the
      control group, TWPs can increase effectiveness, while decreasing erythrocyte
      sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), and
      risk of adverse events. TWPs treatment was also more effective than treatment by
      conventional western medicine (CWM) and Chinese patent medicine or placebo (COP).
      TWPs significantly decreased the risk of adverse events compared with the CWM
      group, but not compared with the COP group. Current evidence shows that TWPs are
      more effective than other western or Chinese medicines we included in this meta
      analysis for RA treatment with relatively lower toxicity.

PMID- 29576792
TI  - Cannabis Essential Oil: A Preliminary Study for the Evaluation of the Brain
      Effects.
AB  - We examined the effects of essential oil from legal (THC <0.2% w/v) hemp variety
      on the nervous system in 5 healthy volunteers. GC/EIMS and GC/FID analysis of the
      EO showed that the main components were myrcene and beta-caryophyllene. The
      experiment consisted of measuring autonomic nervous system (ANS) parameters;
      evaluations of the mood state; and electroencephalography (EEG) recording before
      treatment, during treatment, and after hemp inhalation periods as compared with
      control conditions. The results revealed decreased diastolic blood pressure,
      increased heart rate, and significant increased skin temperature. The subjects
      described themselves as more energetic, relaxed, and calm. The analysis EEG
      showed a significant increase in the mean frequency of alpha (8-13 Hz) and
      significant decreased mean frequency and relative power of beta 2 (18,5-30 Hz)
      waves. Moreover, an increased power, relative power, and amplitude of theta (4-8
      Hz) and alpha brain waves activities and an increment in the delta wave (0,5-4
      Hz) power and relative power was recorded in the posterior region of the brain.
      These results suggest that the brain wave activity and ANS are affected by the
      inhalation of the EO of Cannabis sativa suggesting a neuromodular activity in
      cases of stress, depression, and anxiety.

PMID- 29576793
TI  - What Factors Guide the Selection of Medicinal Plants in a Local Pharmacopoeia? A
      Case Study in a Rural Community from a Historically Transformed Atlantic Forest
      Landscape.
AB  - The criteria that local people use for selecting medicinal plants have been a
      recurrent topic in pharmacology and ethnobotany. Two of the current hypotheses
      regarding this phenomenon, ecological apparency and diversification, attempt to
      explain the inclusion of "apparent" and "non-apparent" and native and exotic
      taxa, respectively, in local pharmacopoeia. This study addresses the following
      questions: Do "apparent" and "non-apparent" medicinal plants have the same
      importance in local pharmacopoeia? Do "non-apparent" plants occupy more local
      categories of diseases than "apparent" plants? Do native and exotic medicinal
      plants have the same importance? Do exotic and native plants occupy different
      local categories of diseases? This study was conducted with householders of a
      community from Northeastern Brazil. Out of the 66 plant species cited, most were
      herbs (39 species), followed by trees and shrubs (27). Herbaceous species also
      occupied more local categories of diseases (51) than tree and shrub species (28).
      Furthermore, most of the species cited by the informants were exotic (42). Out of
      the 94 therapeutic applications cited in this research, 65 were treated with
      exotic species and 29 with native species, distributed among 13 body systems.
      These results support both the hypotheses of ecological apparency and
      diversification.

PMID- 29576794
TI  - The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong
      Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - Oligoasthenozoospermia is a crucial factor in male infertility. Wuzi Yanzong
      (WZYZ) pill is a popular traditional Chinese medicine (TCM) formula which has
      been used for male infertility treatment for years. However, its effects on semen
      quality remain controversial. We conducted a preregistered meta-analysis to
      assess the effect of WZYZ pill for the therapeutic effects on
      oligoasthenozoospermia. Five randomized controlled trials including 960
      participants were selected from databases of domains in North-East Asian regions,
      PubMed, Embase, and Cochrane Library. WZYZ pill group yielded a greater mean
      increment on sperm concentration (5 trials: MD 5.99, 95% CI 2.12-9.85, P =
      0.002), sperm motility (5 trials: MD 4.57, 95% CI 0.47-8.68, P = 0.03), sperm
      morphology (2 trials: MD -1.93, 95% CI -4.87-1.01, P = 0.20), activity of
      acrosomal enzyme (2 trials: MD 28.27, 95% CI 12.41-44.14, P < 0.01), volume of
      semen (2 trials: MD 0.56, 95% CI 0.21-0.91, P = 0.002), and a decrement of sperm
      DNA fragmentation index (2 trials: MD -3.82, 95% CI -6.45--1.19, P = 0.004).
      However, qualities of selected studies were generally unsatisfactory, and there
      was inherent heterogeneity among some of the outcomes. Despite these limitations,
      the WZYZ pill improved sperm quality by improving several semen parameters and
      decreasing DNA damage in oligoasthenozoospermia patients.

PMID- 29576795
TI  - Effects of Qingshen Granules on the Oxidative Stress-NF/kB Signal Pathway in
      Unilateral Ureteral Obstruction Rats.
AB  - Background. The activation of NF-kappa B (NF/kB) signaling pathway plays an
      important role in the process of epithelial-mesenchymal transition (EMT) and
      renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative
      stress reaction in kidney is via excessive reactive oxygen species (ROS)
      production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an
      effective Chinese formula utilized to treat chronic renal failure. Previous
      studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction
      (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on
      oxidative stress and the activation of NF/kB signaling. Seventy male Sprague
      Dawley (SD) rats were randomly divided into a sham group, UUO model group,
      Qingshen Granules (QSG) high-dose, medium-dose, and low-dose groups, PDTC group,
      and candesartan group (10 rats in each group). Our study demonstrated that
      oxidative stress-NF/kB signal pathway contributed to the formation of UUO renal
      interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative
      stress-NF/kB signal pathway, reducing inflammation, and improving renal tubular
      EMT.

PMID- 29576796
TI  - Apocynum venetum Leaf Extract Exerts Antidepressant-Like Effects and Inhibits
      Hippocampal and Cortical Apoptosis of Rats Exposed to Chronic Unpredictable Mild
      Stress.
AB  - We investigated the effects of Apocynum venetum leaf extract (AVLE) on depressive
      behaviors and neuronal apoptosis in a chronic unpredictable mild stress (CUMS)
      rat model of depression. Rats were randomly divided into six groups: control,
      chronic unpredictable mild stress, fluoxetine, AVLE30, AVLE60, and AVLE120.
      Except for the control group, all rats were submitted to chronic unpredictable
      mild stress paradigms for four weeks to induce depressive behavior. Neuronal
      apoptosis was assessed by the terminal deoxynucleotidyl transferase- (TDT-)
      mediated dUTP-biotin nick end-labeling (TUNEL) method. The expression levels of
      apoptosis-related proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2 Associated X
      Protein (Bax), cysteine-aspartic acid protease-3 and protease-9 (caspase-3 and
      caspase-9), cytochrome c (cyt-C), brain-derived neurotrophic factor (BDNF), and
      cAMP-response element binding (CREB) protein, were evaluated by western blot.
      Treatment with AVLE (60 or 120 mg/kg/day) significantly improved depressive
      behavior. Increased apoptosis of hippocampus and cortical neurons were observed
      in CUMS rats, while 120 mg/kg/day of AVLE significantly reversed these changes
      and achieved the best antidepressant-like effects among the doses tested.
      Moreover, AVLE (120 mg/kg) significantly increased Bcl-2, BDNF, and CREB protein
      expression and decreased Bax, cyt-C, and caspase family protein expression. Our
      results indicate that AVLE has potent antidepressant activity, likely due to its
      ability to suppress neuronal apoptosis.

PMID- 29576797
TI  - Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome
      Activation.
AB  - Arctium lappa (A. lappa), Compositae, is considered a potential source of
      nutrition and is used as a traditional medicine in East Asian countries for
      centuries. Although several studies have shown its biological activities as an
      anti-inflammatory agent, there have been no reports on A. lappa with regard to
      regulatory role in inflammasome activation. The purpose of this study was to
      investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3
      inflammasome activation and explore the underlying mechanisms. We found that ALE
      inhibited IL-1beta secretion from NLRP3 inflammasome activated bone marrow
      derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes
      activation. Mechanistic studies revealed that ALE suppressed the ATPase activity
      of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS)
      generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on
      NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase
      function and attenuated the mROS during inflammasome activation. In addition, ALE
      significantly reduced the LPS-induced increase of plasma IL-1beta in mouse
      peritonitis model. These results provide evidence of novel anti-inflammatory
      mechanisms of A. lappa, which might be used for therapeutic applications in the
      treatment of NLRP3 inflammasome-associated inflammatory disorders.

PMID- 29576798
TI  - Jinkui Shenqi Pills Ameliorate Asthma with "Kidney Yang Deficiency" by Enhancing
      the Function of the Hypothalamic-Pituitary-Adrenal Axis to Regulate T Helper 1/2
      Imbalance.
AB  - The aim of the study was to investigate the effects and underlying mechanism of
      JKSQP in a rat model of asthma with kidney-yang deficiency (KYD). Materials and
      Methods. Hydrocortisone (HYD) was used to establish the rat model of KYD; rats
      were then sensitized and challenged with ovalbumin (OVA). JKSQP was administered
      to OVA-challenged rats, and the changes in signs and symptoms of KYD were
      observed. The leukocyte number and subpopulations in bronchoalveolar lavage fluid
      (BALF) were counted and the cells were stained with Wright-Giemsa dye. Serum
      adrenocorticotropic hormone (ACTH), corticosterone (CORT), corticotropin
      releasing hormone (CRH), total immunoglobulin E (IgE), and OVA-specific IgE
      levels were determined using relevant enzyme-linked immunosorbent assays (ELISA)
      kits. Results. JKSQP not only reversed the phenomenon of KYD but also
      significantly inhibited the number of leukocyte and eosinophils in the BALF,
      increasing the level of interferon (IFN)-gamma and decreasing the levels of
      interleukin-4 (IL-4) and IgE in the serum compared with the OVA-challenged
      groups. Conclusions. Taken together, the antiasthma effects of JKSQP were likely
      mediated by the enhancement of the function of the hypothalamic-pituitary-adrenal
      axis and the reversal of T helper 1/2 imbalance.

PMID- 29576799
TI  - Advanced Effect of Moringa oleifera Bioconversion by Rhizopus oligosporus on the
      Treatment of Atopic Dermatitis: Preliminary Study.
AB  - This study was conducted to determine if topical application of Moringa oleifera
      extracts and its bioconversion product fermented by Rhizopus oligosporus has
      therapeutic properties enhancement for treatment of atopic dermatitis. Rhizopus
      oligosporus (KCCM 11232P) was used to ferment Moringa leaves' extracts in this
      study. Comparison of organic acids and flavonols in Moringa simple extracts and
      their fermented product by HPLC analysis revealed that concentration of organic
      acids and flavonols of bioconversion product was lower than that of hot water
      extracts. The fermentation process is used as a nutrient for isolation of each
      component by microorganisms and growth of microorganisms. The results
      demonstrated that MF extracts effectively reduced clinical features based on
      macrography, scratching count, and severity scores, as well as model's serum IgE
      level, including histopathological analyses.

PMID- 29576800
TI  - Effects of Huanglian Jiedu Decoration in Rat Gingivitis.
AB  - Gingivitis is an inflammatory disease that affects gingival tissues through a
      microbe-immune interaction. Huanglian Jiedu decoction (HLJD) is used
      traditionally for clearing and detoxifying in China, which had been reported to
      possess many pharmacological effects. Rat gingival inflammation model was
      established by lipopolysaccharide (LPS) injection for 3 consecutive days, and
      HLJD was given by gavage before LPS injection. After 3 days rats were sacrificed
      and tissue samples were evaluated. Serum cytokine levels such as interleukin-6
      (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked
      immunoabsorbent assay (ELISA). Oxidative stress related molecules such as total
      antioxidant capacity (T-AOC), malondialdehyde (MDA), and reactive oxygen species
      (ROS) were determined. Expression of AMP-activated protein kinase (AMPK) and
      extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway were
      inspected by western blotting. Histological changes of gingival tissues were
      tested with hematoxylin-eosin (HE) staining. HLJD significantly decreased serum
      levels of IL-6 and TNF-alpha, suppressed generation of MDA and ROS, and enhanced
      T-AOC creation. Moreover, HLJD inhibited expressions of AMPK and ERK1/2. The
      inflammation severity of gingival tissue by HE staining was severe in model group
      but relieved in HLJD group obviously. HLJD exhibited protective effects against
      gingival damage through suppressing inflammation reaction and elevating
      antioxidation power.

PMID- 29576801
TI  - Antibacterial Effects of Leaf Extract of Nandina domestica and the Underlined
      Mechanism.
AB  - Aim: The study was conducted to investigate the antibacterial and antiasthmatic
      effects of Nandina domestica leaf extract, to find out its active components, and
      to assess its safety issue. Methods: (1) Solid-phase agar dilution method was
      used for antibacterial activity test of nandina leaf extract and the change of
      bacterial morphology after treatment was observed under the transmission
      microscope; (2) guinea pig model of asthma was used to test the asthma prevention
      effect of nandina leaf extract; (3) alkaloids and flavones were separated from
      nandina leaf extract and were further analyzed with HPLC-MS; (4) mice model was
      used to assessment of the safety issue of nandina leaf extract. Results: (1)
      Nandina leaf extract inhibited the growth of bacteria and destroyed bacterial
      membrane; (2) nandina leaf extract alleviated animal allergy and asthma; (3) the
      components reextracted by ethyl acetate were active, in which alkaloids inhibited
      Gram-positive bacteria and prevented asthma and flavones inhibited Gram-negative
      bacteria; (4) nandina leaf extract had no toxic effect on mice. Conclusion:
      Nandina leaves inhibit bacterial growth and prevent asthma through alkaloids and
      flavones, which had integrated function against chronic bronchitis. This study
      provided theoretical basement for producing new Chinese medicine against chronic
      bronchitis.

PMID- 29576802
TI  - Antiosteoarthritic Effects of ChondroT in a Rat Model of Monosodium Iodoacetate
      Induced Osteoarthritis.
AB  - Ganghwaljetongyeum is a traditional Korean herbal medicine used to treat joint
      pain, limited motion, fever, and swelling; it also inhibits inflammatory
      processes associated with arthritis. ChondroT, a water extract of
      Ganghwaljetongyeum, is a new complex herbal medicine. This study investigated the
      effects of ChondroT using a rat model of monosodium iodoacetate- (MIA-) induced
      osteoarthritis. Thirty-six rats were randomly divided into three ChondroT groups
      and a normal, control, and positive control group. Changes in paw edema volume,
      histopathology, and plantar withdrawal response were analyzed. Further,
      inflammatory cytokines, arachidonic acids, liver and kidney function, and
      hematological features were measured. ChondroT significantly decreased paw edema
      by the 5th day and notably improved articular cartilage damage; it also
      significantly improved the plantar withdrawal response in terms of both reaction
      time and force intensity. Moreover, treatment with ChondroT significantly
      decreased the serum levels of tumor necrosis factor alpha, interleukin-1beta,
      interleukin-6, and prostaglandin E2 and significantly increased serum aspartate
      aminotransferase and alanine aminotransferase levels. This study demonstrates
      that ChondroT has anti-inflammatory and analgesic effects in a MIA-induced
      osteoarthritis rat model. These results support the clinical relevance of
      ChondroT for future use in patients with osteoarthritis. However, further studies
      are required to elucidate the corresponding mechanisms.

PMID- 29576803
TI  - Materials library collections as tools for interdisciplinary research.
AB  - This paper examines how materials libraries are used as tools for
      interdisciplinary collaboration in 3 research projects that inhabit a
      disciplinary triangle between materials research, design and user needs:
      PhysFeel, which explores how materials collections can be used in psychological
      therapies; Light.Touch.Matters, a design-led project to develop new smart
      materials; and Hands of X, which uses materials collections to develop a bespoke
      prosthetics service. The paper analyses and contrasts these case studies to
      better understand the affordances and limitations of materials collections when
      used as research, translational and design tools. We conclude that in
      collaborations between materials researchers, designers and end users, tensions
      arise as a result of the primacy that each partner gives to creativity, the
      development of new knowledge and to solving societal problems. The use of a
      materials library addresses many of these issues but is not a panacea for all the
      problems associated with interdisciplinary working.

PMID- 29576804
TI  - Nanofibre optic force transducers with sub-piconewton resolution via near-field
      plasmon-dielectric interactions.
AB  - Ultrasensitive nanomechanical instruments, including the atomic force microscope
      (AFM)1-4 and optical and magnetic tweezers5-8, have helped shed new light on the
      complex mechanical environments of biological processes. However, it is difficult
      to scale down the size of these instruments due to their feedback mechanisms9,
      which, if overcome, would enable high-density nanomechanical probing inside
      materials. A variety of molecular force probes including mechanophores10, quantum
      dots11, fluorescent pairs12,13 and molecular rotors14-16 have been designed to
      measure intracellular stresses; however, fluorescence-based techniques can have
      short operating times due to photo-instability and it is still challenging to
      quantify the forces with high spatial and mechanical resolution. Here, we develop
      a compact nanofibre optic force transducer (NOFT) that utilizes strong near-field
      plasmon-dielectric interactions to measure local forces with a sensitivity of
      <200 fN. The NOFT system is tested by monitoring bacterial motion and heart-cell
      beating as well as detecting infrasound power in solution.

PMID- 29576805
TI  - Dietary Compound Proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et
      Zucc.) leaves inhibit angiogenesis and regulate cell cycle of cisplatin-resistant
      ovarian cancer cells via targeting Akt pathway.
AB  - Ovarian cancer is the leading cause of death from gynecological malignancy and
      natural products have drawn great attention for cancer treatment. Chinese
      bayberry leaves proanthocyanidin (BLPs) with epigallocatechin-3-O-gallate (EGCG)
      as its terminal and major extension units is unusual in the plant kingdom. In the
      present study, BLPs showed strong growth inhibitory effects on cisplatin
      resistant A2780/CP70 cells by inhibiting angiogenesis and inducing G1 cell cycle
      arrest. BLPs reduced the tube formation in HUVECs and attenuated the wound
      healing ability in A2780/CP70 cells. BLPs further reduced the level of ROS and
      targeted Akt/mTOR/p70S6K/4E-BP-1 pathway to reduce the expression of HIF-1alpha
      and VEGF, and thus inhibited angiogenesis. Furthermore, BLPs induced G1 cell
      cycle arrest by reducing the expressions of c-Myc, cyclin D1 and CDK4, which was
      also in accordance with the flow cytometry analysis. Overall, these results
      indicated that BLPs could be a valuable resource of natural compounds for cancer
      treatment.

PMID- 29576806
TI  - Genomic Analysis of Propane Metabolism in Methyl Tert-Butyl Ether-Degrading
      Mycobacterium Sp. Strain ENV421.
AB  - Methyl tert-butyl ether (MTBE) is a ground water contaminant with plausible
      carcinogenic properties. Mycobacterium sp. strain ENV421 cometabolically degrades
      MTBE and other ethers during the growth on propane as a carbon source. In this
      study, the 6.2 Mb genome of strain ENV421 was deciphered. The genome sequence
      revealed the presence of numerous putative propane catabolic genes including
      genes encoding hydrocarbon oxygenases and short chain alcohol dehydrogenases.
      These data provide the basis for the elucidation of propane metabolic pathways in
      strain ENV421 and its application for the remediation of ground water
      contaminated with toxic ethers.

PMID- 29576807
TI  - Complete Genome Sequence of Microcystis aeruginosa NIES-2481 and Common Genomic
      Features of Group G M. aeruginosa.
AB  - Microcystis aeruginosa is a freshwater bloom-forming cyanobacterium that is
      distributed worldwide. M. aeruginosa can be divided into at least 8 phylogenetic
      groups (A-G and X) at the intraspecific level. Here, we report the complete
      genome sequence of M. aeruginosa NIES-2481, which was isolated from Lake
      Kasumigaura, Japan, and is assigned to group G. The complete genome sequence of
      M. aeruginosa NIES-2481 comprises a 4.29-Mbp circular chromosome and a 147,539-bp
      plasmid; the circular chromosome and the plasmid contain 4,332 and 167 protein
      coding genes, respectively. Comparative analysis with the complete genome of M.
      aeruginosa NIES-2549, which belongs to the same group with NIES-2481, showed that
      the genome size is the smallest level in previously sequenced M. aeruginosa
      strains, and the genomes do not contain a microcystin biosynthetic gene cluster
      in common. Synteny analysis revealed only small-scale rearrangements between the
      two genomes.

PMID- 29576808
TI  - Important parameters for optimized metal nanoparticles-aided electromagnetic
      field (EMF) effect on cancer.
AB  - Background: A number of experimental research findings for the metal
      nanoparticles (NPs)-mediated EMF photothermal therapy of cancer cells show an
      intriguing trend of the NPs' size-dependent efficacy. This is a phenomenon we
      find to trend with the light absorption bandwidth behavior (full width at half
      maximum) of the NPs and the accompanying electric field enhancement. We find that
      the nanoparticle sizes that have been reported to produce the optimized effect on
      cancer cells are of minimum absorption bandwidth and optimized electric field
      magnitude. While the death of cancer cells under the NPs-aided EMF effect has in
      the past attracted varied interpretations, either as a thermal or non-thermal
      effect, photothermal effect has gained a wide acceptance due to the exhibited
      hyperthermia. However, the exhibited trend of the NPs' size-dependent efficacy is
      beginning to feature as a possible manifestation of other overlooked underlying
      or synergistic phenomenal conditions. Method: We present a theoretical model and
      analysis which reveal that the contribution and efficacy of the metal NPs in the
      destruction of cancer depend partly but significantly on the accompanying
      electric field intensity enhancement factor and partly on their absorption cross
      section. Results: This paper finds that, other than the expected hyperthermia,
      the metal NPs' sizes for the optimized therapy on cancer cells seem to fulfill
      other synergistic conditions which need to come to the fore. We find interplay
      between electric field and thermal effects as independent energy channels where
      balancing may be important for the optimized EMF effect, in the ratio of about
      5:1. The required balancing depends on the absorption bandwidth and absorption
      cross-section of the NPs, the frequency of EMF used and the relative permittivity
      of the cancer cells. The NPs' size-dependent efficacy decreases away from the
      NPs' size of minimum absorption bandwidth, which is around 20 nm for Au NPs or
      other shapes of equivalent surface area-volume ratio. While the absorption
      wavelength peak for metal NPs would change with the change of shape, the
      responsible condition(s) for optimizing the efficacy remains relatively
      invariable. Conclusion: From the modeling and the analysis of the NPs' size for
      optimizing the EMF therapy on cancer cells, the ratio of electric field
      enhancement by metal NPs to the associated thermal effect is a very important
      factor for efficacy.

PMID- 29576809
TI  - Observational Study on a Mindfulness Training for Smokers within a Smoking
      Cessation Program.

PMID- 29576810
TI  - A Unified Mechanism for the Water Hammer Pulse and Pulsus Bisferiens in Severe
      Aortic Regurgitation: Insights from Wave Intensity Analysis.

PMID- 29576811
TI  - Delineating Potential Transcriptomic Association with Organochlorine Pesticides
      in the Etiology of Epithelial Ovarian Cancer.
AB  - Background: Recent studies have shown that there is an increased risk of
      Epithelial Ovarian Cancer (EOC) with Organochlorine Pesticides (OCPs). However,
      the alteration in the gene expression profile has not been explored so far. The
      goal of the present study is to understand the probable molecular mechanism of
      OCPs toxicity towards discovery of dysregulation of signaling pathway associated
      with differential gene expression and candidate transcriptomic set of markers in
      the pathophysiology of EOC in OCPs exposed population. Methods: The OCP levels
      were estimated by gas chromatography and whole genome differential expression
      study was carried out using expression microarray and candidate genes were
      validated using Real time RT-PCR. Results: Significant level of OCP residues such
      as beta-hexachlorocyclohexane (beta-HCH), Heptachlor, Heptachlor epoxide B
      (HTEB), dichlorodiphenyldichloroethylene (p'p'-DDE) and endosulfan-I was found
      between healthy and EOC patients. The transcriptome profile of several genes
      revealed regulation of various important cellular processes such as metabolism,
      inflammation, cytoskeleton dysregulation of TGF and WNT pathway in EOC cases with
      high OCPs. Conclusion: This study provides the first evidence showing that
      differentially expressed genes and dysregulation of signaling pathways might be
      associated with significant level of OCPs exposure in ovary tissue of epithelial
      ovarian cancer patients. Moreover, significant correlation of these genes with
      OCPs revealed that OCPs exposure played vital role in dysregulation of related
      pathways in the etiology of EOC.

PMID- 29576812
TI  - Cognitive and Language Deficits in Multiple Sclerosis: Comparison of Relapsing
      Remitting and Secondary Progressive Subtypes.
AB  - Objective: The objective of this study was to investigate the pattern and
      severity of cognitive and language impairment in Greek patients with Relapsing
      remitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS), relative to
      control participants. Method: A prospective study was conducted in 27 patients
      with multiple sclerosis (PwMS), (N= 15) with RRMS, (N= 12) with SPMS, and (N= 12)
      healthy controls. All participants were assessed with a flexible comprehensive
      neuropsychological - language battery of tests that have been standardized in
      Greece and validated in Greek MS patients. They were also assessed on measures of
      disability (Expanded Disability Status Scale; EDSS), fatigue (Fatigue Severity
      Scale; FSS) and depression (Beck Depression Inventory - fast screen; BDI-FS).
      Results: Our results revealed that groups were well matched on baseline
      demographic and clinical characteristics. The two clinical groups (RRMS; SPMS)
      did not differ on overall global cognitive impairment but differed in the initial
      encoding of verbal material, mental processing speed, response inhibition and set
      shifting. RRMS patients differed from controls in the initial encoding of verbal
      material, learning curve, delayed recall of verbal information, processing speed,
      and response inhibition. SPMS patients differed in all utilized measures compared
      to controls. Moreover, we noted increased impairment frequency on individualized
      measures in the progressive SPMS group. Conclusion: We conclude that MS patients,
      irrespective of clinical subtype, have cognitive deficits compared to healthy
      participants, which become increasingly worse when they convert from RRMS to
      SPMS.On the contrary,the pattern of impairment remains relatively stable.

PMID- 29576813
TI  - Determining the Actual Prevalence of Hepatitis B in Khyber Pakhtunkhwa-Pakistan:
      A Meta-Analysis.
AB  - Background: Hepatitis B is considered the most dangerous among the five types of
      Hepatitis, as it is clinically asymptomatic. It can silently damage the liver
      over many years without being diagnosed. Hepatitis B is one of the top risks of
      liver complications in Khyber Pakhtunkhwa (KP), a province of Pakistan, with an
      average prevalence rate of 2.70%. Aims: We aimed to carefully review the
      previously published data on prevalence of Hepatitis B Virus (HBV) in KP-Pakistan
      and use the statistical approach to obtain more precise estimate of the
      prevalence of HBV in KP-Pakistan. This study on one hand will provide a more
      reliable and consolidated estimate (pooled estimate) of HBV in the stated region,
      on the other hand, it enabled us to judge the heterogeneity among the estimates
      found from these studies. The study is intended to provide more authentic
      prevalence record and help government/ non-government organizations and health
      professionals, which plan to initiate HBV prevention programs in KP-Pakistan.
      Methods: A meta-analysis was performed based on studies found in literature
      search from electronic databases and bibliography on the prevalence of HBV in KP
      Pakistan from 2007 to 2017. Abstracts and results of twenty papers were
      thoroughly studied and the data were extracted. The findings from these studies
      were distributed in two groups (general and population at high risk) constituting
      15 and 5 studies respectively. Results: The combined prevalence by considering
      random model for the general population of KP-Pakistan was observed to be 2.71%,
      while population at high risk was reasonably high i.e. 5.64%. By comparing this
      prevalence rate to the highest global prevalence of HBV in the adult population
      of Western Pacific Region (6.2%), significant (p-value= 0.000) heterogeneity was
      observed among the estimates in each group. However, the funnel plot provides a
      symmetric look, eliminating the effect of publication bias. We can say that HBV
      has an alarming prevalence rate in KP-Pakistan. However, HBV is thrice more
      prevalent in male population of KP-Pakistan than the female population.
      Conclusion: The above results lead that HBV infection has reached an alarming
      state in KP-Pakistan, though projects like Prime Minister's Program for
      Prevention & Control of Hepatitis which are contributing in improving the health
      of the people of KP by trying to prevent and control the incidence of HBV. More
      massive vaccination and awareness programs should be initiated to prevent the
      spread of HBV on urgent basis. Provision of diagnostics and treatment facilities
      against HBV in healthcare units of KP-Pakistan should be assured.

PMID- 29576814
TI  - Preliminary Data From the Study of Coagulative Profile of HIV Infected
      Individuals Suggest a Role For Point Mutations in the Gene in Protein S
      Deficiency in Individuals Undergoing Highly Antiretroviral Therapy.
AB  - Background: HIV infection is a known prothrombotic condition but factors involved
      are still controversial. A role for antiretrovirals, especially protease
      inhibitors, was advocated. Objectives: The study aimed to analyze the levels of
      anticoagulant proteins in virally suppressed HIV-infected subjects treated with
      different anti-retroviral regimens. Materials and Methods: Forty-four patients
      were included in the study. C and PS, D-Dimers and Fibrinogen levels were
      determined as well as APC-resistance. PROS1 gene was sequenced in a group of
      patient. Results: Twelve of the 44 subjects (27%) showed reduced levels of PS,
      while lower levels of PC were found only in 2 patients (4,5%). No difference in
      the mean values of PC and PS was found stratifying the study population by
      antiretroviral regimen administrated (p>0.05).Three patients had higher levels of
      D-Dimer concentrations and in two of these patients, an association between
      higher D-Dimer values and lower levels of PS was observed; but however no
      correlation was found by statistical analysis.PROS1 gene analysis was performed
      in 26 of the 44 HIV-1 patients and the subjects with low levels of PS had
      mutation in the fifteen exon of PROS 1 gene. While among individuals with normal
      levels, this mutation was observed only in 8/18 (44%) of the cases (p=0,0072).
      Conclusion: The majority of patients with low PS levels also had mutations in the
      fifteen exon of PROS 1 gene. Genetic determinants, deserving further
      investigations, rather than antiretrovirals might cause PS deficiency in HIV-1
      positive patients.

PMID- 29576815
TI  - Modification of Initial Highly Active Antiretroviral Therapy (HAART) Regimen in
      Paediatric HIV Patients.
AB  - Background: Treatment options among Human Immunodeficiency Virus (HIV)-infected
      children are limited as only a few Highly Active Antiretroviral Therapy (HAART)
      are approved worldwide for paediatric use. Among children, frequent changes in
      HAART regimen can rapidly exhaust treatment options, and information addressing
      this issue is scarce. Objective: The aim of the study was to determine factors
      associated with the modification of initial HAART regimen modification among HIV
      infected children. Method: A retrospective study was performed among HIV-infected
      children aged 18 and below, that received HAART for at least six months in a
      tertiary hospital in Malaysia. Factors associated with modification of initial
      HAART regimen were investigated. Results: Out of 99 patients, 71.1% (n=71)
      required initial HAART regime modification. The most common reason for HAART
      modification was treatment failure (n=39, 54.9%). Other reasons included drug
      toxicity (n=14, 19.7%), change to fixed-dose products (n=11, 15.5%), product
      discontinuation (n=4, 5.6%) and intolerable taste (n=3, 4.2%). The overall mean
      time retention on initial HAART before regimen modification was 3.32 year +/-
      2.24 years (95% CI, 2.79-3.85). Patient's adherence was the only factor
      associated with initial regimen modification in this study. Participants with
      poor adherence showed a five-fold risk of having their initial HAART regimen
      modified compared to those with good adherence (adjusted OR [95% CI], 5.250
      [1.614 - 17.076], p = 0.006). Conclusion: Poor adherence was significantly
      associated with initial regimen modification, intervention to improve patient's
      adherence is necessary to prevent multiple regimen modification among HIV
      infected children.

PMID- 29576816
TI  - Why it Worked: Participants' Insights into an mHealth Antiretroviral Therapy
      Adherence Intervention in China.
AB  - Background: Few Antiretroviral Therapy (ART) adherence trials investigate the
      reasons for intervention success or failure among HIV-positive individuals.
      Objectives: To conduct qualitative research to explore the reasons for
      effectiveness of a 6-month mHealth (mobile health) trial that improved adherence
      among ART patients in China. The intervention utilized Wireless Pill Containers
      (WPCs) to provide, real-time SMS reminders, WPC-generated adherence reports, and
      report-informed counseling. Methods: We conducted in-depth interviews with 20
      intervention-arm participants immediately following the trial. Sampling was
      purposeful to ensure inclusion of participants with varied adherence histories.
      Questions covered adherence barriers and facilitators, and intervention
      experiences. We analyzed data in nVivo using a thematic approach. Results: Of
      participants, 14 (70%) were male; 7 (35%) had used injectable drugs. Pre
      intervention, 11 were optimal adherers and 9 were suboptimal adherers, using a
      95% threshold. In the final intervention month, all but 3 (85%) attained optimal
      adherence. Participants identified a range of adherence barriers and
      facilitators, and described various mechanisms for intervention success. Optimal
      adherers at baseline were motivated by positive adherence reports at monthly
      clinic visits-similar to receiving A+ grades. For suboptimal adherers, reminders
      facilitated the establishment of adherence-promoting routines; data-guided
      counseling helped identify strategies to overcome specific barriers. Conclusion:
      Different behavioral mechanisms appear to explain the success of an mHealth
      adherence intervention among patients with varying adherence histories. Positive
      reinforcement was effective for optimal adherers, while struggling patients
      benefitted from reminders and data-informed counseling. These findings are
      relevant for the design and scalability of mHealth interventions and warrant
      further investigation.

PMID- 29576817
TI  - Neuropsychological Features of Multiple Sclerosis: Impact and Rehabilitation.

PMID- 29576818
TI  - Aeolian dune sediment flux heterogeneity in Meridiani Planum, Mars.
AB  - It is now known unambiguously that wind-driven bedform activity is occurring on
      the surface of Mars today, including early detections of active sand dunes in
      Meridiani Planum's Endeavour crater. Many of these reports are only based on a
      few sets of observations of relatively isolated bedforms and lack regional
      context. Here, we investigate aeolian activity across central Meridiani Planum
      and test the hypothesis that dune sites surrounding Endeavour crater are also
      active and part of region-wide sediment migration driven by northwesterly winds.
      All 13 dune fields investigated clearly showed evidence for activity and the
      majority exhibited dune migration (average rates of 0.6 m/Earth-year).
      Observations indicate substantial geographic and temporal heterogeneity of dune
      crest fluxes across the area and per site. Locations with multiple time steps
      indicate dune sand fluxes can vary by a factor of five, providing evidence for
      short periods of rapid migration followed by near-stagnation. In contrast,
      measurements at other sites are nearly identical, indicating that some dunes are
      in a steady-state as they migrate. The observed sediment transport direction was
      consistent with a regional northeasterly-to-northwesterly wind regime, revealing
      more variations than were appreciated from earlier, more localized studies.
      Craters containing shallow, degraded, flat-floored interiors tended to have dunes
      with high sediment fluxes/activity, whereas local kilometer-scale topographic
      obstructions (e.g., central peaks, yardangs) were found to be inversely
      correlated with dune mobility. Finally, the previous, more limited detections of
      dune activity in Endeavour crater have been shown to be representative of a
      broader, region-wide pattern of dune motion.

PMID- 29576819
TI  - Effect of angioembolisation versus surgical packing on mortality in traumatic
      pelvic haemorrhage: A systematic review and meta-analysis.
AB  - BACKGROUND: The management of complex pattern of bleeding associated with pelvic
      trauma remains a big challenge for trauma surgeons. We aimed to conduct a
      comprehensive meta-analysis to compare the outcomes of angioembolisation and
      pelvic packing in patients with pelvic trauma. METHODS: We conducted a systematic
      search of electronic information sources, including MEDLINE; EMBASE; CINAHL; the
      CENTRAL; the World Health Organization International Clinical Trials Registry;
      ClinicalTrials.gov; ISRCTN Register, and bibliographic reference lists. The
      primary outcome was defined as mortality. Combined overall effect sizes were
      calculated using random-effects models. Results are reported as the odds ratio
      (OR) and 95% confidence interval (CI). RESULTS: We identified 3 observational
      studies reporting a total of 120 patients undergoing angioembolisation (n=60) or
      pelvic packing (n=60) for pelvic trauma. Reporting of the Injury Severity Score
      (ISS) was variable, with higher ISS in the pelvic packing group. The risk of bias
      was low in two studies, and moderate in one. The pooled analysis demonstrated
      that angioembolisation did not significantly reduce mortality in patients with
      pelvic trauma compared to surgery (OR=1.99; 95% CI= 0.83-4.78, P=0.12). There was
      mild between-study heterogeneity (I2=0%, P=0.65). CONCLUSION: Our analysis found
      no significant difference in mortality between angioembolisation and pelvic
      packing in patients with traumatic pelvic haemorrhage. The current level of
      evidence in this context is very limited and insufficient to support the
      superiority of a treatment modality. Future research is required.

PMID- 29576820
TI  - The Emergency Department Crash Cart: A systematic review and suggested contents.
AB  - BACKGROUND: As the field of Emergency Medicine grows worldwide, the importance of
      an Emergency Department Crash Cart (EDCC) has long been recognized. Yet, there is
      paucity of relevant peer-reviewed literature specifically discussing EDCCs or
      proposing detailed features for an EDCC suitable for both adult and pediatric
      patients. METHODS: The authors performed a systematic review of EDCC-specific
      literature indexed in Pubmed and Embase on December 20, 2016. In addition, the
      authors reviewed the 2015 American Heart Association (AHA) guidelines for
      cardiopulmonary resuscitation and emergency cardiovascular care, the 2015
      European Resuscitation Council (ERC) guidelines for resuscitation, and the 2013
      American College of Surgeons (ACS) Advanced Trauma Life Support (ATLS) 9th
      edition. RESULTS: There were a total of 277 results, with 192 unique results and
      85 duplicates. After careful review by two independent reviewers, all but four
      references were excluded. None of the four included articles described
      comprehensive contents of equipment and medications for both the adult and
      pediatric populations. This article describes in detail the final four articles
      specific to EDCC, and proposes a set of suggested contents for the EDCC.
      CONCLUSION: Our systematic review shows the striking paucity of such a high
      impact indispensable item in the ED. We hope that our EDCC content suggestions
      help enhance the level of response of EDs in the resuscitation of adult and
      pediatric populations, and encourage the implementation of and adherence to the
      latest evidence-based resuscitation guidelines.

PMID- 29576821
TI  - Video versus direct laryngoscopy on successful first-pass endotracheal intubation
      in ICU patients.
AB  - BACKGROUND: Airway management in intensive care unit (ICU) patients is
      challenging. The aim of this study was to compare the rate of successful first
      pass intubation in the ICU by using the direct laryngoscopy (DL) and that by
      using the video laryngoscopy (VL). METHODS: A randomized, non-blinded trial
      comparing first-pass success rate of intubation between VL and DL was performed.
      Patients were recruited in the period from August 2014 to August 2016. All
      physicians working at ICU received hands-on training in the use of the video and
      direct laryngoscope. The primary outcome measure was the first-pass intubation
      success. RESULTS: A total of 163 ICU patients underwent intubation during the
      study period (81 patients in VL group and 82 in DL group). The rate of successful
      first-pass intubation was not significantly different between the VL and the DL
      group (67.9% vs. 69.5%, P=0.824). Moreover, the overall intubation success and
      total number of attempts to achieve intubation success did not differ between the
      two groups. In patients with successful first-pass intubation, the median
      duration of the intubation procedure did not differ between the two groups. The
      Cormack-Lehane grades and the percentage of glottic opening score were similar,
      and no significant differences were found between the two groups. There were no
      statistical differences between the VL and the DL group in intubation
      complications (all P>0.05). CONCLUSION: Among ICU patients requiring intubation,
      there was no significant difference in the rate of successful first-pass
      intubation between VL and DL.

PMID- 29576822
TI  - Predisposing factors, clinical assessment, management and outcomes of agitation
      in the trauma intensive care unit.
AB  - BACKGROUND: Agitation occurs frequently among critically ill patients admitted to
      the intensive care unit (ICU). We aimed to evaluate the frequency, predisposing
      factors and outcomes of agitation in trauma ICU. METHODS: A retrospective
      analysis was conducted to include patients who were admitted to the trauma ICU
      between April 2014 and March 2015. Data included patient's demographics, initial
      vitals, associated injuries, Ramsey Sedation Scale, Glasgow Coma Scale, head
      injury lesions, use of sedatives and analgesics, head interventions, ventilator
      days, and ICU length of stay. Patients were divided into two groups based on the
      agitation status. RESULTS: A total of 102 intubated patients were enrolled; of
      which 46 (45%) experienced agitation. Patients in the agitation group were 7
      years younger, had significantly lower GCS and sustained higher frequency of head
      injuries (P<0.05). Patients who developed agitation were more likely to be
      prescribed propofol alone or in combination with midazolam and to have frequent
      ICP catheter insertion, longer ventilatory days and higher incidence of pneumonia
      (P<0.05). On multivariate analysis, use of propofol alone (OR=4.97; 95% CI=1.35
      18.27), subarachnoid hemorrhage (OR=5.11; 95% CI=1.38-18.91) and ICP catheter
      insertion for severe head injury (OR=4.23; 95% CI=1.16-15.35) were independent
      predictors for agitation (P<0.01). CONCLUSION: Agitation is a frequent problem in
      trauma ICU and is mainly related to the type of sedation and poor outcomes in
      terms of prolonged mechanical ventilation and development of nosocomial
      pneumonia. Therefore, understanding the main predictors of agitation facilitates
      early risk-stratification and development of better therapeutic strategies in
      trauma patients.

PMID- 29576823
TI  - Outcomes of severe sepsis and septic shock patients after stratification by
      initial lactate value.
AB  - BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases
      when lactate levels are >= 4 mmol/L. However, the consequences of lower lactate
      levels in this population are not well understood. The study aimed to determine
      the in-hospital mortality associated with severe sepsis and septic shock when
      initial lactate levels are < 4 mmol/L. METHODS: This is a retrospective cohort
      study of septic patients admitted over a 40-month period. Totally 338 patients
      were divided into three groups based on initial lactate values. Group 1 had
      lactate levels < 2 mmol/L; group 2: 2-4 mmol/L; and group 3: >= 4 mmol/L. The
      primary outcome was in-hospital mortality. RESULTS: There were 111 patients in
      group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were
      21.6%, 35.4%, and 51.9% respectively. Univariate analysis revealed the mortality
      differences to be statistically significant. Multivariate logistic regression
      demonstrated higher odds of death with higher lactate tier group, however the
      findings did not reach statistical significance. CONCLUSION: This study found
      that only assignment to group 3, initial lactic acid level of >= 4 mmol/L, was
      independently associated with increased mortality after correcting for underlying
      severity of illness and organ dysfunction. However, rising lactate levels in the
      other two groups were associated with increased severity of illness and were
      inversely proportional to prognosis.

PMID- 29576824
TI  - Ventilator management for acute respiratory distress syndrome associated with
      avian influenza A (H7N9) virus infection: A case series.
AB  - BACKGROUND: Data on the mechanical ventilation (MV) characteristics and
      radiologic features for the cases with H7N9-induced ARDS were still lacking.
      METHODS: We describe the MV characteristics and radiologic features of adult
      patients with ARDS due to microbiologically confirmed H7N9 admitted to our ICU
      over a 3-month period. RESULTS: Eight patients (mean age 57.38+/-16.75; 5 male)
      were diagnosed with H7N9 in the first quarter of 2014. All developed respiratory
      failure complicated by acute respiratory distress syndrome (ARDS), which required
      MV in ICU. The baseline APACHE II and SOFA score was 11.77+/-6.32 and 7.71+/
      3.12. The overall CT scores of the patients was 247.68+/-34.28 and the range of
      CT scores was 196.3-294.7. The average MV days was 14.63+/-6.14, and 4 patients
      required additional rescue therapies for refractory hypoxemia. Despite these
      measures, 3 patients died. CONCLUSION: In H7N9-infected patients with ARDS, low
      tidal volume strategy was the conventional mode. RM as one of rescue therapies to
      refractory hypoxemia in these patients with serious architectural distortion and
      high CT scores, which could cause further lung damage, may induce bad outcomes
      and requires serious consideration. Prone ventilation may improve mortality, and
      should be performed at the early stage of the disease, not as a rescue therapy.

PMID- 29576825
TI  - Comparison of sedative effectiveness of thiopental versus midazolam in reduction
      of shoulder dislocation.
AB  - BACKGROUND: Various sedative drugs have been proposed to control anxiety and
      agitation in shoulder dislocation, but none of them has been diagnosed as the
      best sedative and relaxant agent. The study aimed to compare the sedative
      effectiveness of thiopental versus midazolam in reduction of shoulder
      dislocation. METHODS: A randomized double-blind controlled trail was performed in
      80 patients with shoulder dislocation recruited from the emergency department.
      Ten patients were excluded and 70 patients were enrolled in the study. Case group
      received intravenous thiopental 2 mg/kg+2 ug/kg fentanyl while control group
      received intravenous midazolam 0.1 mg/kg+2 ug/kg fentanyl. Number of times,
      patients and physician's satisfaction, difficulty of procedure, degree of muscle
      relaxation, time of sedation and complete recovery, number of patients with apnea
      episode, O2 saturation, patient's pain score and adverse events were all
      recorded. RESULTS: Muscular tone had significant difference between the two
      groups (P-value=0.014) and thiopental was more muscle relaxant than midazolam.
      Replacement of shoulder dislocation in thiopental group was easier than midazolam
      group (P-value=0.043). There was no need to use multiple methods of reduction in
      either group. Before drug infusion the mean+/-SD VAS scores were 8.37+/-2.21 in
      the midazolam group (A) and 8.94+/-1.78 in the thiopental group (B); mean
      difference 0.57, 95% CI= -0.38 to 1.52. After completion of the procedure, the
      mean+/-SD VAS scores in group (A) and (B) were 3.20+/-1.30 vs. 3.65+/-1.30; mean
      difference -0.45, 95% CI= -1.07 to 0.16. CONCLUSION: Thiopental might be more
      effective and relaxant than midazolam for reduction of shoulder dislocation.

PMID- 29576826
TI  - The relative value of education of emergency physicians in patient outcome: A
      retrospective analysis at a single center in developing India.
AB  - BACKGROUND: There is a considerable paucity with regards to the research
      available on the quality and quantity of clinical teaching in the national
      emergency department (ED) setups. With the onset of the age of modern medicine,
      the outlook towards to the time worn tradition of triage and detailed medical
      evaluation must be revoked. Despite the variety of programs being conducted in
      the country, a comparable entity common to all is patients' clinical outcomes
      which can be measured using simple parameters which can be easily acquired
      compiling hospital registry entries. METHODS: A retrospective observational study
      was conducted in the emergency department of Max Hospital, Saket, New Delhi. A
      period of 22 months prior to the start of the program and like-wise 22 months
      after initiation of the program was collected from the hospital registry. The
      Emergency Medicine program in consideration was the Masters in emergency Medicine
      (MEM) Program affiliated with George Washington University, NY, USA. Patients of
      all age groups and gender registering in the Emergency Department and so were all
      the doctors working in the ED before and after initiation of the program.
      RESULTS: An improvement was noted in terms of total admissions through the ED per
      month, average length of stay of admitted as well as discharged patients; return
      to ED within 24 hours; leave against medical advice and patient complaints. A
      reduction was noted in number of discharges from the ED. Despite a numerical
      worsening on the patient's death in ED a graphical improvement can be noted
      considering the month wise representation of data. CONCLUSION: We can make a
      coherent conclusion that there is an improvement in the outcome of the entire
      patient related aspects in the Emergency Department considering the all two time
      frames included in the study. The difference can be very well attributed to the
      integration of the structural Academic Program in the development of the
      Emergency Physicians. This leads us to make a conclusive analysis regarding a
      positive impact of the Relative Value of Education of Emergency Physicians not
      only in patient outcome but also in physicians and administrative outlook towards
      an overall better emergency care.

PMID- 29576827
TI  - Impact of an educational intervention on medical records documentation.
AB  - BACKGROUND: Inaccurate and incomplete documentation can lead to poor treatment
      and medico-legal consequences. Studies indicate that teaching programs in this
      field can improve the documentation of medical records. The study aimed to
      evaluate the effect of an educational workshop on medical record documentation by
      emergency medicine residents in the emergency department. METHODS: An
      interventional study was performed on 30 residents in their first year of
      training emergency medicine (PGY1), in three tertiary referral hospitals of
      Tehran University of Medical Sciences. The essential information that should be
      documented in a medical record was taught in a 3-day-workshop. The medical
      records completed by these residents before the training workshop were randomly
      selected and scored (300 records), as was a random selection of the records they
      completed one (300 records) and six months (300 records) after the workshop.
      RESULTS: Documentation of the majority of the essential items of information was
      improved significantly after the workshop. In particular documentation of the
      patients' date and time of admission, past medical and social history.
      Documentation of patient identity, requests for consultations by other
      specialties, first and final diagnoses were 100% complete and accurate up to 6
      months of the workshop. CONCLUSION: This study confirms that an educational
      workshop improves medical record documentation by physicians in training.

PMID- 29576828
TI  - Characteristics and outcomes of out-of-hospital cardiac arrest in Zhejiang
      Province.

PMID- 29576829
TI  - Computed tomography angiography-negative aortic dissection in a patient using
      Phencyclidine.

PMID- 29576830
TI  - Point-of-care ultrasound identification of yolk stalk sign in a case of failed
      first trimester pregnancy.

PMID- 29576831
TI  - Acute atraumatic pinna (auricular) perichondritis.

PMID- 29576832
TI  - Responding to fire in an intensive care unit: Management and lessons learned.

PMID- 29576833
TI  - Evaporation-induced monolayer compression improves droplet interface bilayer
      formation using unsaturated lipids.
AB  - In this article, we report on a new experimental methodology to enable reliable
      formation of droplet interface bilayer (DIB) model membranes with two types of
      unsaturated lipids that have proven difficult for creating stable DIBs. Through
      the implementation of a simple evaporation technique to condition the
      spontaneously assembled lipid monolayer around each droplet, we increased the
      success rates of DIB formation for two distinct unsaturated lipids, namely 1,2
      dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC), from less than 10% to near 100%. Separately, using a
      pendant drop tensiometer, we learned that: (a) DOPC and POPC monolayers do not
      spontaneously assemble into their tightest possible configurations at an oil
      water interface, and (b) reducing the surface area of a water droplet coated with
      a partially packed monolayer leads to a more tightly packed monolayer with an
      interfacial tension lower than that achieved by spontaneous assembly alone. We
      also estimated from Langmuir compression isotherms obtained for both lipids that
      the brief droplet evaporation procedure prior to DIB formation resulted in a 6%
      16% reduction in area per lipid for DOPC and POPC, respectively. Finally, the
      increased success rates of formation for DOPC and POPC DIBs enabled quantitative
      characterization of unsaturated lipid membrane properties including electrical
      resistance, rupture potential, and specific capacitance.

PMID- 29576834
TI  - Microfluidic platform for selective microparticle parking and paired particle
      isolation in droplet arrays.
AB  - Immobilizing microscale objects (e.g., cells, spheroids, and microparticles) in
      arrays for direct observation and analysis is a critical step of many biological
      and chemical assays; however, existing techniques are often limited in their
      ability to precisely capture, arrange, isolate, and recollect objects of
      interest. In this work, we present a microfluidic platform that selectively parks
      microparticles in hydrodynamic traps based on particle physical characteristics
      (size, stiffness, and internal structure). We present an accompanying scaling
      analysis for the particle parking process to enable rational design of
      microfluidic traps and selection of operating conditions for successful parking
      of desired particles with specific size and elastic modulus. Our platform also
      enables parking of encoded particle pairs in defined spatial arrangements and
      subsequent isolation of these pairs in aqueous droplets, creating distinct
      microenvironments with no cross-contamination. In addition, we demonstrate the
      ability to recollect objects of interest (i.e., one particle from each pair)
      after observation within the channel. This integrated device is ideal for
      multiplexed assays or microenvironment fabrication for controlled biological
      studies.

PMID- 29576835
TI  - A rapid and meshless analytical model of acoustofluidic pressure fields for
      waveguide design.
AB  - Acoustofluidics has a strong pedigree in microscale manipulation, with particle
      and cell separation and patterning arising from acoustic pressure gradients.
      Acoustic waveguides are a promising candidate for localizing force fields in
      microfluidic devices, for which computational modelling is an important design
      tool. Meshed finite element analysis is a popular approach for this, yet its
      computation time increases rapidly when complex geometries are used, limiting its
      usefulness. Here, we present an analytical model of the acoustic pressure field
      in a microchannel arising from a surface acoustic wave (SAW) boundary condition
      that computes in milliseconds and provide the simulation code in the
      supplementary material. Unlike finite element analysis, the computation time of
      our model is independent of microchannel or waveguide shape, making it ideal for
      designing and optimising microscale waveguide structures. We provide experimental
      validation of our model with cases including near-field acoustic patterning of
      microparticles from a travelling SAW and two-dimensional patterning from a
      standing SAW and explore the design of waveguides for localised particle or cell
      capture.

PMID- 29576836
TI  - Hairpins in the conformations of a confined polymer.
AB  - If a semiflexible polymer confined to a narrow channel bends around by 180
      degrees , the polymer is said to exhibit a hairpin. The equilibrium extension
      statistics of the confined polymer are well understood when hairpins are
      vanishingly rare or when they are plentiful. Here, we analyze the extension
      statistics in the intermediate situation via experiments with DNA coated by the
      protein RecA, which enhances the stiffness of the DNA molecule by approximately
      one order of magnitude. We find that the extension distribution is highly non
      Gaussian, in good agreement with Monte-Carlo simulations of confined discrete
      wormlike chains. We develop a simple model that qualitatively explains the form
      of the extension distribution. The model shows that the tail of the distribution
      at short extensions is determined by conformations with one hairpin.

PMID- 29576837
TI  - Enhanced separation of aged RBCs by designing channel cross section.
AB  - Prolonged storage will alter the biophysical properties of red blood cells
      (RBCs), and it decreases the quality of stored blood for blood transfusion. It
      has been known that less deformable aged RBCs can be separated by margination,
      but the recognition of the storage time from the separation efficiency of the
      stiff RBCs is still a challenge. In this study, we realized enhanced separation
      of aged RBCs from normal RBCs by controlling the channel cross section and
      demonstrated that the storage time can be deduced from the percentage of the
      separated RBCs in the stored RBCs. This separation technology helps to reveal the
      regulation of time on the RBC aging mechanism and offer a new method to separate
      stiffened cells with high efficiency.

PMID- 29576838
TI  - A low cost, membranes based serum separator modular.
AB  - To fulfill the requirement of sample preparation in a microfluidic analysis
      system designed for "sample in, answer out" testing which was urgently needed by
      resource limited clinical facilities, we proposed a critical low cost, membrane
      based serum separator design in this article. With a specially designed
      microchip, this device can easily separate serum from the whole blood sample in 5
      min. Different from techniques which have been reported earlier, this approach
      does not require either centrifugation or sample dilution which may cause
      hemolysis or decreased testing sensitivity. By applying 300 MUl of the whole
      blood sample, 50-70 MUl of serum can be recovered from each device, and the serum
      volume recovery rate compared with centrifuged control is around 73% which is
      sufficient for most of the microfluidic-based assays. The protein recovery rate
      ranged from 70% to 95% which was compared with centrifuged control. The
      evaluation results indicate that this sample preparation device can offer
      sufficient amount of purified serum sample for any kind of diagnostic assays such
      as immunoassay and serum nucleic acid assay.

PMID- 29576839
TI  - Simultaneous detection of multiple HPV DNA via bottom-well microfluidic chip
      within an infra-red PCR platform.
AB  - Portable Polymerase Chain Reaction (PCR) devices combined with microfluidic chips
      or lateral flow stripes have shown great potential in the field of point-of-need
      testing (PoNT) as they only require a small volume of patient sample and are
      capable of presenting results in a short time. However, the detection for
      multiple targets in this field leaves much to be desired. Herein, we introduce a
      novel PCR platform by integrating a bottom-well microfluidic chip with an infra
      red (IR) excited temperature control method and fluorescence co-detection of
      three PCR products. Microfluidic chips are utilized to partition different
      samples into individual bottom-wells. The oil phase in the main channel contains
      multi-walled carbon nanotubes which were used as a heat transfer medium that
      absorbs energy from the IR-light-emitting diode (LED) and transfers heat to the
      water phase below. Cyclical rapid heating and cooling necessary for PCR are
      achieved by alternative power switching of the IR-LED and Universal Serial Bus
      (USB) mini-fan with a pulse width modulation scheme. This design of the IR-LED
      PCR platform is economic, compact, and fully portable, making it a promising
      application in the field of PoNT. The bottom-well microfluidic chip and IR-LED
      PCR platform were combined to fulfill a three-stage thermal cycling PCR for 40
      cycles within 90 min for Human Papilloma Virus (HPV) detection. The PCR
      fluorescent signal was successfully captured at the end of each cycle. The
      technique introduced here has broad applications in nucleic acid amplification
      and PoNT devices.

PMID- 29576840
TI  - Molecular-Fluorescence Enhancement via Blue-Shifted Plasmon-Induced Resonance
      Energy Transfer.
AB  - We report molecular-fluorescence enhancement via the blue-shifted plasmon-induced
      resonance energy transfer (PIRET) from single Au nanorods (AuNRs) to merocyanine
      (MC) dye molecules. The blue-shifted PIRET occurs when there is a proper spectral
      overlap between the scattering of AuNRs and the absorption of MC molecules. Along
      with the quenching of scattering from AuNRs, the blue-shifted PIRET enhances the
      fluorescence of nearby molecules. On the basis of the fluorescence enhancement,
      we conclude that AuNRs can be used as donors with clear advantages to excite the
      fluorescence of molecules as acceptors in AuNR-molecule hybrids. On the one hand,
      compared to conventional molecular donors in Forster resonance energy transfer
      (FRET), AuNRs have much larger absorption cross sections at the plasmon resonance
      frequencies. On the other hand, energy-transfer efficiency of PIRET decreases at
      a lower rate than that of FRET when the donor-acceptor distance is increased.
      Besides, the blue-shifted PIRET allows excitation with incident light of lower
      energy than the acceptor's absorption, which is difficult to achieve in FRET
      because of the Stokes shift. With the capability of enhancing molecular
      fluorescence with excitation light of low intensity and long wavelength, the blue
      shifted PIRET will expand the applications of nanoparticle- molecule hybrids in
      biosensing and bioimaging by increasing signal-to-noise ratio and by reducing
      photodamage to biological cells and organelles at the targeted areas.

PMID- 29576841
TI  - Different Setting Conditions Affect Surface Characteristics and Microhardness of
      Calcium Silicate-Based Sealers.
AB  - Objective: To investigate the effect of different setting conditions on surface
      microhardness and setting properties of calcium silicate-based sealers. Methods:
      Three sealers, EndoSequence Bioceramic (BC; Brasseler USA, Savannah, GA, USA),
      Endoseal MTA (ES; Maruchi, Wonju, Korea), and Well-Root ST (WR; Vericom,
      Chuncheon, Korea), were compared. Specimens were exposed to either butyric acid
      (pH 5.4) or phosphate-buffered saline (PBS [pH 7.4]) for 48 h and stored at 100%
      humidity for 12 days. The control specimens were stored at 100% humidity for 14
      days. Surface microhardness was measured, topographic changes were observed, and
      phase analysis was performed using X-ray diffraction. Microhardness according to
      storage conditions was compared using one-way analysis of variance and Tukey's
      multiple comparison tests (P < .05). Results: The BC and ES sealers exhibited
      decreased microhardness when stored in acid or PBS compared with control (P <
      .05). In the WR group, acid exposure lowered microhardness of the specimens
      compared with control (P < .05). Scanning electron microscopy revealed different
      topographies in specimens from all tested sealers exposed to acid or PBS.
      Conclusion: The surface microhardness of calcium silicate-based sealers was
      reduced by exposure to either acid or PBS. Acid solutions, however, had a more
      detrimental effect than PBS.

PMID- 29576842
TI  - Baseline Air Quality Assessment of Goods Movement Activities before the Port of
      Charleston Expansion: A Community-University Collaborative.
AB  - As the demand for goods continues to increase, a collective network of
      transportation systems is required to facilitate goods movement activities. This
      study examines air quality near the Port of Charleston before its expansion and
      briefly describes the establishment and structure of a community-university
      partnership used to monitor existing pollution. Particulate matter (PM)
      concentrations (PM2.5 and PM10) were measured using the Thermo Fisher Scientific
      Partisol 2000i-D Dichotomous Air Sampler, Thermo Scientific Dichotomous
      Sequential Air Sampler Partisol-Plus 2025-D, and Rupprecht & Patashnick TEOM
      Series 1400 Sampler at neighborhood (Union Heights, Rosemont, and Accabee) and
      reference (FAA2.5 and Jenkins Street) sites. Descriptive statistics were
      performed and an ANOVA (analysis of variance) was calculated to find the
      difference in overall mean 24-hour PM average concentrations in communities
      impacted by environmental injustice. PM2.5 (15.2 MUg/m3) and PM10 (27.2 MUg/m3)
      maximum concentrations were highest in neighborhoods such as Union Heights
      neighborhoods due to more goods movement activities. Nevertheless, there was no
      statistically significant difference in mean concentrations of PM2.5 and PM10
      across neighborhood sites. In contrast, mean PM10 neighborhood concentrations
      were significantly lower than mean PM10 reference concentrations for Union
      Heights (p = 0.00), Accabee (p <= 0.0001), and Rosemont (p = 0.01). Although PM
      concentrations were lower than current National Ambient Air Quality Standards,
      this study demonstrated how community-university partners can work collectively
      to document baseline PM concentrations that will be used to examine changes in
      air quality after the port expansion brings additional goods movement activities
      to the area.

PMID- 29576844
TI  - Mitochondrial Structure, Function, and Dynamics: The Common Thread across Organs,
      Disease, and Aging.

PMID- 29576843
TI  - Modulation of Adipocyte Differentiation and Proadipogenic Gene Expression by
      Sulforaphane, Genistein, and Docosahexaenoic Acid as a First Step to Counteract
      Obesity.
AB  - Obesity is characterized by excess body fat accumulation due to an increase in
      the size and number of differentiated mature adipocytes. Adipocyte
      differentiation is regulated by genetic and environmental factors, and its
      inhibition could represent a strategy for obesity prevention and treatment. The
      current study was designed with two aims: (i) to evaluate the changes in the
      expression of adipogenic markers (C/EBPalpha, PPARgamma variant 1 and variant 2,
      and GLUT4) in 3T3-L1 murine preadipocytes at four stages of the differentiation
      process and (ii) to compare the effectiveness of sulforaphane, genistein, and
      docosahexaenoic acid in reducing lipid accumulation and modulating C/EBPalpha,
      PPARgamma1, PPARgamma2, and GLUT4 mRNA expression in mature adipocytes. All
      bioactive compounds were shown to suppress adipocyte differentiation, although
      with different effectiveness. These results set the stage for further studies
      considering natural food constituents as important agents in preventing or
      treating obesity.

PMID- 29576845
TI  - Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of
      Horminum pyrenaicum in Human PBMC.
AB  - Several phytochemicals were shown to interfere with redox biology in the human
      system. Moreover, redox biochemistry is crucially involved in the orchestration
      of immunological cascades. When screening for immunomodulatory compounds, the two
      interferon gamma- (IFN-gamma-) dependent immunometabolic pathways of tryptophan
      breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1) and neopterin formation by
      GTP-cyclohydrolase 1 (GTP-CH-I) represent prominent targets, as IFN-gamma-related
      signaling is strongly sensitive to oxidative triggers. Herein, the analysis of
      these pathway activities in human peripheral mononuclear cells was successfully
      applied in a bioactivity-guided fractionation strategy to screen for anti
      inflammatory substances contained in the root of Horminum (H.) pyrenaicum L.
      (syn. Dragon's mouth), the only representative of the monophyletic genus
      Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O
      acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural
      product), two nor-abietane diterpene quinones (agastaquinone and 3
      deoxyagastaquinone) and two abeo 18 (4 -> 3) abietane diterpene quinones (agastol
      and its 15,16-dehydro-derivative) could be identified. These compounds were able
      to dose-dependently suppress the above mentioned pathways with different potency.
      Beside the description of new active compounds, this study demonstrates the
      feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel
      anti-inflammatory compounds, which can then be directed towards a more detailed
      mode of action analysis.

PMID- 29576846
TI  - Proscillaridin A Promotes Oxidative Stress and ER Stress, Inhibits STAT3
      Activation, and Induces Apoptosis in A549 Lung Adenocarcinoma Cells.
AB  - Cardiac glycosides are natural compounds used for the treatment of cardiovascular
      disorders. Although originally prescribed for cardiovascular diseases, more
      recently, they have been rediscovered for their potential use in the treatment of
      cancer. Proscillaridin A (PSD-A), a cardiac glycoside component of Urginea
      maritima, has been reported to exhibit anticancer activity. However, the cellular
      targets and anticancer mechanism of PSD-A in various cancers including lung
      cancer remain largely unexplored. In the present study, we found that PSD-A
      inhibits growth and induces apoptosis in A549 lung adenocarcinoma cells. The
      anticancer activity of PSD-A was found to be associated with the activation of
      JNK, induction of ER stress, mitochondrial dysfunction, and inhibition of STAT3
      activation. PSD-A induces oxidative stress as evidenced from ROS generation, GSH
      depletion, and decreased activity of TrxR1. PSD-A-mediated ER stress was verified
      by increased phosphorylation of eIF2alpha and expression of its downstream
      effector proteins ATF4, CHOP, and caspases-4. PSD-A triggered apoptosis by
      inducing JNK (1/2) activation, increasing bax/bcl-2 ratio, dissipating
      mitochondrial membrane potential, and inducing cleavage of caspases and PARP.
      Further study revealed that PSD-A inhibits both constitutive and inducible STAT3
      activations and decreases STAT3 DNA-binding activity. Moreover, PSD-A-mediated
      inhibition of STAT3 activation was found to be associated with increased SHP-1
      expression, decreased phosphorylation of Src, and binding of PSD-A with STAT3 SH2
      domain. Finally, STAT3 knockdown by shRNA inhibited growth and enhanced apoptotic
      efficacy of PSD-A. Taken together, the data suggest that PSD-A could be developed
      into a potential therapeutic agent against lung adenocarcinoma.

PMID- 29576847
TI  - Differentiation of Promonocytic U937 Cells to Monocytes Is Associated with
      Reduced Mitochondrial Transport of Ascorbic Acid.
AB  - Growth of promonocytic U937 cells in the presence of DMSO promotes their
      differentiation to monocytes. After 4 days of culture in differentiating medium,
      these cells ceased to proliferate, displayed downregulated ryanodine receptor
      expression, and responded to specific stimuli with enhanced NADPH-oxidase-derived
      superoxide formation or cytosolic phospholipase A2-dependent arachidonic acid
      release. We found that the 4-day differentiation process is also associated with
      downregulated SVCT2 mRNA expression, in the absence of apparent changes in SVCT2
      protein expression and transport rate of ascorbic acid (AA). Interestingly, under
      the same conditions, these cells accumulated lower amounts of the vitamin in
      their mitochondria, with an ensuing reduced response to external stimuli
      sensitive to the mitochondrial fraction of AA. Further analyses demonstrated an
      unexpected increase in mitochondrial SVCT2 protein expression, however,
      associated with reduced SVCT2-dependent AA uptake in isolated mitochondria. A
      decrease in the transporter Vmax, with no change in affinity, was found to
      account for this response. Differentiation of promonocytic cells to monocytes is
      therefore characterized by decreased SVCT2 mRNA expression that, even prior to
      the onset of SVCT2 protein downregulation or apparent changes in plasma membrane
      transport activity, impacts on the mitochondrial accumulation of the vitamin
      through a decreased Vmax of the transporter.

PMID- 29576848
TI  - The Ratio of Plasma and Urinary 8-oxo-Gsn Could Be a Novel Evaluation Index for
      Patients with Chronic Kidney Disease.
AB  - Nucleic acid oxidation plays an important role in the pathophysiology progress of
      a variety of diseases. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) and 8-oxo
      7,8-dihydroguanosine (8-oxo-Gsn), which originate from DNA and RNA oxidation,
      were the most widely used indicators for oxidative stress. The study investigated
      the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD. 146 patients with CKD were
      divided into five disease stages, and their fasting blood and morning urine were
      collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were
      quantified by LC-MS/MS. The ratio of urinary 8-oxo-Gsn to creatinine increased
      from stages 1 to 4 corresponding to the increased severity of CKD, but it
      decreased in stage 5. And plasma 8-oxo-Gsn gradually increased with the decline
      of renal function. In particular, the increased ratio of plasma and urine 8-oxo
      Gsn in stage 5 exceeded the concentration of creatinine. This trend was similar
      to the estimated glomerular filtration rate (eGFR), which indicates that 8-oxo
      Gsn could be an appropriate indicator for renal function. Our finding indicates
      that as the disease progresses, RNA oxidation is increased. The significant
      increase in the ratio of plasma and urinary 8-oxo-Gsn is a novel evaluation index
      of end-stage renal disease.

PMID- 29576849
TI  - Palmitoylethanolamide Dampens Reactive Astrogliosis and Improves Neuronal Trophic
      Support in a Triple Transgenic Model of Alzheimer's Disease: In Vitro and In Vivo
      Evidence.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder responsible for the
      majority of dementia cases in elderly people. It is widely accepted that the main
      hallmarks of AD are not only senile plaques and neurofibrillary tangles but also
      reactive astrogliosis, which often precedes detrimental deposits and neuronal
      atrophy. Such phenomenon facilitates the regeneration of neural networks;
      however, under some circumstances, like in AD, reactive astrogliosis is
      detrimental, depriving neurons of the homeostatic support, thus contributing to
      neuronal loss. We investigated the presence of reactive astrogliosis in 3*Tg-AD
      mice and the effects of palmitoylethanolamide (PEA), a well-documented anti
      inflammatory molecule, by in vitro and in vivo studies. In vitro results revealed
      a basal reactive state in primary cortical 3*Tg-AD-derived astrocytes and the
      ability of PEA to counteract such phenomenon and improve viability of 3*Tg-AD
      derived neurons. In vivo observations, performed using ultramicronized- (um-)
      PEA, a formulation endowed with best bioavailability, confirmed the efficacy of
      this compound. Moreover, the schedule of treatment, mimicking the clinic use
      (chronic daily administration), revealed its beneficial pharmacological
      properties in dampening reactive astrogliosis and promoting the glial
      neurosupportive function. Collectively, our results encourage further
      investigation on PEA effects, suggesting it as an alternative or adjunct
      treatment approach for innovative AD therapy.

PMID- 29576850
TI  - Transcriptome Remodeling of Differentiated Cells during Chronological Ageing of
      Yeast Colonies: New Insights into Metabolic Differentiation.
AB  - We present the spatiotemporal metabolic differentiation of yeast cell
      subpopulations from upper, lower, and margin regions of colonies of different
      ages, based on comprehensive transcriptomic analysis. Furthermore, the analysis
      was extended to include smaller cell subpopulations identified previously by
      microscopy within fully differentiated U and L cells of aged colonies. New data
      from RNA-seq provides both spatial and temporal information on cell metabolic
      reprogramming during colony ageing and shows that cells at marginal positions are
      similar to upper cells, but both these cell types are metabolically distinct from
      cells localized to lower colony regions. As colonies age, dramatic metabolic
      reprogramming occurs in cells of upper regions, while changes in margin and lower
      cells are less prominent. Interestingly, whereas clear expression differences
      were identified between two L cell subpopulations, U cells (which adopt metabolic
      profiles, similar to those of tumor cells) form a more homogeneous cell
      population. The data identified crucial metabolic reprogramming events that arise
      de novo during colony ageing and are linked to U and L cell colony
      differentiation and support a role for mitochondria in this differentiation
      process.

PMID- 29576851
TI  - Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein
      Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase
      Pathways.
AB  - RNA-binding protein dysregulation and altered expression of proteins involved in
      the autophagy/proteasome pathway play a role in many neurodegenerative disease
      onset/progression, including age-related macular degeneration (AMD). HuR/ELAVL1
      is a master regulator of gene expression in human physiopathology. In ARPE-19
      cells exposed to the proteasomal inhibitor MG132, HuR positively affects at
      posttranscriptional level p62 expression, a stress response gene involved in
      protein aggregate clearance with a role in AMD. Here, we studied the early
      effects of the proautophagy AICAR + MG132 cotreatment on the HuR-p62 pathway. We
      treated ARPE-19 cells with Erk1/2, AMPK, p38MAPK, PKC, and JNK kinase inhibitors
      in the presence of AICAR + MG132 and evaluated HuR localization/phosphorylation
      and p62 expression. Two-hour AICAR + MG132 induces both HuR cytoplasmic
      translocation and threonine phosphorylation via the Erk1/2 pathway. In these
      conditions, p62 mRNA is loaded on polysomes and its translation in de novo
      protein is favored. Additionally, for the first time, we report that JNK can
      phosphorylate HuR, however, without modulating its localization. Our study
      supports HuR's role as an upstream regulator of p62 expression in ARPE-19 cells,
      helps to understand better the early events in response to a proautophagy
      stimulus, and suggests that modulation of the autophagy-regulating kinases as
      potential therapeutic targets for AMD may be relevant.

PMID- 29576852
TI  - ZP2495 Protects against Myocardial Ischemia/Reperfusion Injury in Diabetic Mice
      through Improvement of Cardiac Metabolism and Mitochondrial Function: The
      Possible Involvement of AMPK-FoxO3a Signal Pathway.
AB  - Coronary heart disease patients with type 2 diabetes were subject to higher
      vulnerability for cardiac ischemia-reperfusion (I/R) injury. This study was
      designed to evaluate the impact of ZP2495 (a glucagon-GLP-1 dual-agonist) on
      cardiac function and energy metabolism after myocardial I/R injury in db/db mice
      with a focus on mitochondrial function. C57BLKS/J-lepr+/lepr+ (BKS) and db/db
      mice received 4-week treatment of glucagon, ZP131 (GLP-1 receptor agonist), or
      ZP2495, followed by cardiac I/R injury. The results showed that cardiac function,
      cardiac glucose metabolism, cardiomyocyte apoptosis, cardiac mitochondrial
      morphology, and energetic transition were improved or ameliorated by ZP2495 to a
      greater extent than that of glucagon and ZP131. In vitro study showed that
      ZP2495, rather than glucagon, alleviated mitochondrial depolarization, cytochrome
      C release, and mitochondria ROS generation in neonatal rat ventricular myocytes
      subjected to high-glucose and simulated I/R injury conditions, the effects of
      which were weaker in the ZP131 group. Furthermore, the expressions of Akt,
      FoxO3a, and AMPK phosphorylation were elevated by ZP2495 to a greater extent than
      that of ZP131. In conclusion, ZP2495 may contribute to the improvement of cardiac
      function and energy metabolism in db/db mice after myocardial I/R injury by
      improving mitochondrial function possibly through Akt/FoxO3a and AMPK/FoxO3a
      signal pathways.

PMID- 29576853
TI  - Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role
      of Oxidative Stress and Bioenergetics in Hyperglycemic Rats.
AB  - Alterations in cardiac energy metabolism play a key role in the pathogenesis of
      diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic
      impairment and oxidative stress has not been well characterized in the cardiac
      function under glycemic control deficiency conditions. This work aimed to
      determine the cardioprotective effects of quercetin (QUE) against the damage
      induced by a high-cholesterol (HC) diet in hyperglycemic rats, addressing
      intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC
      induced alterations in the lipid profile and glycemia in rats. In addition, QUE
      attenuated cardiac diastolic dysfunction (increased E:A ratio), prevented cardiac
      cholesterol accumulation, and reduced the increase in HC-induced myocyte density.
      Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in
      GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant
      enzymatic activity. Quercetin also counteracted HC-induced bioenergetic
      impairment, preventing a reduction in ATP levels and alterations in PGC-1alpha,
      UCP2, and PPARgamma expression. In conclusion, the mechanisms that support the
      cardioprotective effect of QUE in rats with HC might be mediated by the
      upregulation of antioxidant mechanisms and improved bioenergetics on the heart.
      Targeting bioenergetics with QUE can be used as a pharmacological approach to
      modulate structural and functional changes of the heart under
      hypercholesterolemic and hyperglycemic conditions.

PMID- 29576854
TI  - Oxygen Concentration and Oxidative Stress Modulate the Influence of Alzheimer's
      Disease Abeta1-42 Peptide on Human Cells.
AB  - Reactive oxygen species (ROS) generated after exposure to ionizing radiation and
      toxic peptides, in mitochondrial metabolism and during aging contribute to damage
      of cell's structural and functional components and can lead to diseases. Monomers
      and small oligomers of amyloid beta (Abeta) peptide, players in Alzheimer's
      disease, are recently suggested to be involved in damaging of neurons, instead of
      extracellular Abeta plaques. We demonstrate that externally applied disaggregated
      Abeta1-42 peptide interacts preferentially with acidic compartments (lysosomes).
      We compared standard cell cultivation (21% O2) to more physiological cell
      cultivation (5% O2). Cells did not exhibit a dramatic increase in ROS and change
      in glutathione level upon 4 MUM Abeta peptide treatment, whereas exposure to 2 Gy
      X-rays increased ROS and changed glutathione level and ATP concentration. The
      occurrence of the 4977 bp deletion in mtDNA and significant protein carbonylation
      were specific effects of IR and more pronounced at 21% O2. An increase in cell
      death after Abeta peptide treatment or irradiation was unexpectedly restored to
      the control level or below when both were combined, particularly at 5% O2.
      Therefore, Abeta peptide at low concentration can trigger neuroprotective
      mechanisms in cells exposed to radiation. Oxygen concentration is an important
      modulator of cellular responses to stress.

PMID- 29576855
TI  - Tetrahydroxystilbene Glucoside Produces Neuroprotection against 6-OHDA-Induced
      Dopamine Neurotoxicity.
AB  - Parkinson's disease (PD) was one of the most common neurodegenerative diseases
      with a slow and progressive loss of dopamine (DA) neurons in the midbrain
      substantia nigra (SN). Neuroinflammation was identified to be an important
      contributor to PD pathogenesis with the hallmark of microglia activation.
      Tetrahydroxystilbene glucoside (TSG) was the main active component extracted from
      Polygonum multiflorum and held amounts of pharmacological activities including
      antioxidant, free radical-scavenging, anti-inflammation, and cardioprotective
      properties. Recent studies demonstrated that TSG exerted neuroprotection from
      several neurodegenerative disease models. However, the underlying mechanisms were
      not completely elucidated. In the present study, rat nigral stereotaxic injection
      of 6-hydroxydopamine- (6-OHDA-) elicited DA neuronal injury was performed to
      investigate TSG-mediated neuroprotection on DA neurons. In addition, primary rat
      midbrain neuron-glia cocultures were applied to explore the mechanisms underlying
      TSG-exerted neuroprotection. Results showed that daily intraperitoneal injection
      of TSG for 14 consecutive days significantly protected DA neurons from 6-OHDA
      induced neurotoxicity and suppressed microglia activation. Similar
      neuroprotection was shown in primary neuron-glia cocultures. In vitro studies
      further demonstrated that TSG inhibited microglia activation and subsequent
      release of proinflammatory factors. Moreover, TSG-mediated neuroprotection was
      closely related with the inactivation of mitogen-activated protein kinase (MAPK)
      signaling pathway. Together, TSG protects DA neurons from 6-OHDA-induced
      neurotoxicity via the inhibition of microglia-elicited neuroinflammation. These
      findings suggest that TSG might hold potential therapeutic effects on PD.

PMID- 29576858
TI  - Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against
      Oxidative Stress.
AB  - In this research work, the antioxidant and metabolomic profiling of seven
      selected medicinally important herbs including Rauvolfia serpentina, Terminalia
      arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and
      Crataegus oxyacantha was performed. The in vivo cardioprotective potential of
      these medicinal plants was evaluated against surgically induced oxidative stress
      through left anterior descending coronary artery ligation (LADCA) in dogs. The
      antioxidant profiling of these plants was done through DPPH and DNA protection
      assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential,
      while the E. cardamom showed poor antioxidative strength even at its high
      concentration. Different concentrations of extracts of the said plants exhibited
      the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA
      merely treated with H2O2. The metabolomic profiling through LC-MS analysis of
      these antioxidants revealed the presence of active secondary metabolites
      responsible for their antioxidant potential. During in vivo analysis, blood
      samples of all treatment groups were drawn at different time intervals to analyze
      the cardiac and hemodynamic parameters. The results depicted that the group
      pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as
      well as hemodynamic parameters near to normal. The histopathological examination
      also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe
      and inexpensive cardioprotective herbal combination could be considered as an
      alternate of synthetic drugs.

PMID- 29576857
TI  - Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in
      the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant
      Capability.
AB  - Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma
      progression, but its related molecular mechanism remains unclear. Flavonoids were
      extracted from C. aurantium and purified by reparative HPLC. Each fraction was
      identified by using electrospray ionisation mass spectrometry (ESI-MS). Three
      main components (naringin, naringenin, and hesperetin) were isolated from C.
      aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and
      hesperetin had no inhibitory function on cell growth. ROS production was
      increased in naringin- and hesperetin-treated groups after one day of culture
      while the level was always lowest in the naringenin-treated group after three
      days of culture. 95 osteosarcoma patients who underwent surgery were assigned
      into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47)
      and control group (CG, received 20 mg placebo daily, n = 48). After an average of
      two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the
      CG group (P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG
      group than in CG group. ROS levels were lower in the NG group than in the CG
      group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression
      and local recurrence in the patients who underwent osteosarcoma surgery by
      improving antioxidant capability.

PMID- 29576860
TI  - Preoperative short-course radiotherapy in rectal cancer patients: results and
      prognostic factors.
AB  - Objective: The purpose of this study was to evaluate the clinical outcome of
      preoperative short-course radiotherapy for rectal cancer patients. Methods: The
      study group comprised 210 patients with pathologically proven resectable rectal
      cancer. Between 2001 and 2013, they were treated preoperatively with short-course
      radiotherapy (25 Gy delivered in five fractions), followed by total mesorectal
      excision. Adjuvant 5-fluorouracil-based chemotherapy was administered at the
      discretion of the treating physician, depending on the pathological stage.
      Results: After a median follow-up of 57 months, the following 5-year survival
      rates were observed: overall survival-66.4%, disease-free survival-67.2%,
      locoregional relapse-free survival-91.7%, and distant metastases-free survival
      71.5%. The local failure was observed in 15 patients. Ten patients (4.8%)
      achieved pathologic complete response. The multivariate analysis demonstrated the
      regional lymph node involvement to be statistically significant for unfavorable
      outcomes in terms of all estimated survival rates. Lymphovascular invasion was
      found to be a strong predictor of survival (HR = 1.68; 95% CI 1.29-3.55) and
      treatment failure (HR = 1.54; 95% CI 1.08-3.34). The presence of positive
      surgical circumferential margin was related to six times higher risk of
      locoregional recurrence. Early and late severe treatment-induced toxicity was
      reported in 1 and 7.6% patients, respectively. Conclusions: Preoperative short
      course radiotherapy followed by total mesorectal excision and adjuvant
      chemotherapy allows to achieve excellent local control and favorable survival
      rates. The treatment-induced toxicity is acceptable.

PMID- 29576861
TI  - A Subband-Specific Deconvolution Model for MTF Improvement in CT.
AB  - The purpose of this research is to achieve uniform spatial resolution in CT
      (computed tomography) images without hardware modification. The main idea of this
      study is to consider geometry optics model, which can provide the approximate
      blurring PSF (point spread function) kernel, which varies according to the
      distance from X-ray tube to each pixel. The FOV (field of view) was divided into
      several band regions based on the distance from X-ray source, and each region was
      deconvolved with different deconvolution kernels. Though more precise calculation
      for the PSF for deconvolution is possible as the number of subbands increases, we
      set the number of subbands to 11. 11 subband settings seem to be a balancing
      point to reduce noise boost, while MTF (modulation transfer function) increase
      still remains. As the results show, subband-wise deconvolution makes image
      resolution (in terms of MTF) relatively uniform across the FOV. The results show
      that spatial resolution in CT images can be uniform across the FOV without using
      additional equipment. The beauty of this method is that it can be applied to any
      CT system as long as we know the specific system parameters and determine the
      appropriate PSF for deconvolution maps of the system. The proposed algorithm
      shows promising result in improving spatial resolution uniformity while avoiding
      the excessive noise boost.

PMID- 29576856
TI  - Macroautophagy and Chaperone-Mediated Autophagy in Heart Failure: The Known and
      the Unknown.
AB  - Cardiac diseases including hypertrophic and ischemic cardiomyopathies are
      increasingly being reported to accumulate misfolded proteins and damaged
      organelles. These findings have led to an increasing interest in protein
      degradation pathways, like autophagy, which are essential not only for normal
      protein turnover but also in the removal of misfolded and damaged proteins.
      Emerging evidence suggests a previously unprecedented role for autophagic
      processes in cardiac physiology and pathology. This review focuses on the major
      types of autophagic processes, the genes and protein complexes involved, and
      their regulation. It discusses the key similarities and differences between
      macroautophagy, chaperone-mediated autophagy, and selective mitophagy structures
      and functions. The genetic models available to study loss and gain of
      macroautophagy, mitophagy, and CMA are discussed. It defines the markers of
      autophagic processes, methods for measuring autophagic activities, and their
      interpretations. This review then summarizes the major studies of autophagy in
      the heart and their contribution to cardiac pathology. Some reports suggest
      macroautophagy imparts cardioprotection from heart failure pathology. Meanwhile,
      other studies find macroautophagy activation may be detrimental in cardiac
      pathology. An improved understanding of autophagic processes and their regulation
      may lead to a new genre of treatments for cardiac diseases.

PMID- 29576859
TI  - Effectiveness and toxicity of conventional radiotherapy treatment for painful
      spinal metastases: a detailed course of side effects after opposing fields versus
      a single posterior field technique.
AB  - Background: Conventional radiotherapy for painful spinal metastases can be
      delivered with a single posterior-anterior (PA) or two opposed anterior-posterior
      (APPA) fields. We studied the effectiveness and toxicity of both techniques and
      studied whether treatment technique was predictive for abdominal and skin
      toxicity. Patients and methods: Within the Dutch Bone Metastasis Study, 343
      patients received 8 Gray in a single fraction or 24 Gray in six fractions for
      painful spinal metastases. Treatment technique was not randomized. At baseline
      and weekly during follow-up, patients reported pain and other physical
      complaints. Any complaint increasing within 4 weeks after treatment was noted as
      a side effect. Pain response was calculated according to international standards,
      taking into account changes in pain score and medication. Repeated measurement
      analyses and multivariate logistic analyses were performed. Results: Patients
      were mainly treated on the thoracic (34%) and lumbar (53%) spine and 73% received
      a PA field. Pain response was similar between both techniques (74%). In patients
      treated at the thoraco-lumbar and lumbar spine, with multiple fractions,
      significantly more abdominal complaints were noticed. In multivariate analysis,
      radiotherapy technique did not predict for side effects. Conclusion: Conventional
      radiotherapy of painful spinal metastases provides limited toxicity. Radiotherapy
      technique is not an independent predictor of abdominal and skin toxicity of
      irradiation.

PMID- 29576862
TI  - A method for analysing small samples of floral pollen for free and protein-bound
      amino acids.
AB  - Pollen provides floral visitors with essential nutrients including proteins,
      lipids, vitamins and minerals. As an important nutrient resource for pollinators,
      including honeybees and bumblebees, pollen quality is of growing interest in
      assessing available nutrition to foraging bees. To date, quantifying the protein
      bound amino acids in pollen has been difficult and methods rely on large amounts
      of pollen, typically more than 1 g. More usual is to estimate a crude protein
      value based on the nitrogen content of pollen, however, such methods provide no
      information on the distribution of essential and non-essential amino acids
      constituting the proteins.Here, we describe a method of microwave-assisted acid
      hydrolysis using low amounts of pollen that allows exploration of amino acid
      composition, quantified using ultra high performance liquid chromatography
      (UHPLC), and a back calculation to estimate the crude protein content of
      pollen.Reliable analysis of protein-bound and free amino acids as well as an
      estimation of crude protein concentration was obtained from pollen samples as low
      as 1 mg. Greater variation in both protein-bound and free amino acids was found
      in pollen sample sizes <1 mg. Due to the variability in recovery of amino acids
      in smaller sample sizes, we suggest a correction factor to apply to specific
      sample sizes of pollen in order to estimate total crude protein content.The
      method described in this paper will allow researchers to explore the composition
      of amino acids in pollen and will aid research assessing the available nutrition
      to pollinating animals. This method will be particularly useful in assaying the
      pollen of wild plants, from which it is difficult to obtain large sample weights.

PMID- 29576863
TI  - Curious case of a calcified food bolus.
AB  - Authors present an 80-year-old male attending with obstructive food bolus.
      Lateral soft tissue neck x-ray demonstrated a suspected calcified foreign body at
      the level of the larynx. Subsequent senior radiological input reported the
      findings as incidental calcification of carotid arteries. ENT surgeons should
      demonstrate increased awareness for potentially calcified soft tissues on
      interpreting such x-rays.

PMID- 29576864
TI  - Factors Influencing Maternal Behavioral Adaptability: Maternal Depressive
      Symptoms and Child Negative Affect.
AB  - In early childhood, parents play an important role in children's socioemotional
      development. As such, parent training is a central component of many
      psychological interventions for young children (Reyno & McGrath, 2006). Maternal
      depressive symptoms have consistently been linked to maladaptive parenting
      behaviors (e.g., disengagement, intrusiveness), as well as to lower parent
      training efficacy in the context of child psychological intervention, suggesting
      that mothers with higher symptomatology may be less able to be adapt their
      behavior according to situational demands. The goal of the current study was to
      examine both maternal and child factors that may influence maternal behavioral
      adaptability. Ninety-one mothers and their toddlers (M =23.93 months, 59% male)
      participated in a laboratory visit during which children engaged in a variety of
      novelty episodes designed to elicit individual differences in fear/withdrawal
      behaviors. Mothers also completed a questionnaire battery. Maternal behavioral
      adaptability was operationalized as the difference in scores for maternal
      involvement, comforting, and protective behavior between episodes in which
      mothers were instructed to refrain from interaction and those in which they were
      instructed to act naturally. Results indicated that when children displayed high
      levels of negative affect in the restricted episodes, mothers with higher levels
      of depressive symptoms were less able to adapt their involved behavior because
      they exhibited low rates of involvement across episodes regardless of instruction
      given. The current study serves as an intermediary step in understanding how
      maternal depressive symptoms may influence daily interactions with their children
      as well as treatment implementation and outcomes, and provides initial evidence
      that maternal internalizing symptoms may contribute to lower behavioral
      adaptability in the context of certain child behaviors due to consistent low
      involvement.

PMID- 29560250
TI  - exprso: an R-package for the rapid implementation of machine learning algorithms.
AB  - Machine learning plays a major role in many scientific investigations. However,
      non-expert programmers may struggle to implement the elaborate pipelines
      necessary to build highly accurate and generalizable models. We introduce exprso,
      a new R package that is an intuitive machine learning suite designed specifically
      for non-expert programmers. Built initially for the classification of high
      dimensional data, exprso uses an object-oriented framework to encapsulate a
      number of common analytical methods into a series of interchangeable modules.
      This includes modules for feature selection, classification, high-throughput
      parameter grid-searching, elaborate cross-validation schemes (e.g., Monte Carlo
      and nested cross-validation), ensemble classification, and prediction. In
      addition, exprso also supports multi-class classification (through the 1-vs-all
      generalization of binary classifiers) and the prediction of continuous outcomes.

PMID- 29576865
TI  - HCC with low- and normal-serum alpha-fetoprotein levels.
AB  - A large database of 1773 HCC patients in Turkey was examined. 41.9% had alpha
      fetoprotein (AFP) levels <20 IU/ml and an additional 16.123% had values between
      20-100 IU/ml. This 58% of the cohort (<100 IU/ml AFP levels) was examined in
      detail. 66% of patients with small (<5 cm) HCCs had low AFP, compared to 49% of
      patients with larger (>5 cm) HCCs. The mean diameter (MTD) of larger MTD, low AFP
      tumors was 8.4cm. Therefore, factors other than AFP must contribute to HCC tumor
      growth. Larger tumors in low AFP patients had both higher platelet levels and
      increased PVT percent. Linear regression analysis for both MTD and multifocality
      showed that platelet numbers and presence of PVT were significant variables;
      whereas for PVT, significant variables were albumin, alkaline phosphatase and
      MTD. Comparisons between patients with AFP levels <20, 20-<100, 100-<1000 and
      >1000 IU/ml showed the most significant tumor finding was an increase in PVT
      percent between each group, and to a lesser extent, MTD. Thus, low- or normal-AFP
      HCCs constitute the majority of patients and have slightly lower MTD and much
      lower PVT percent than HCCs associated with elevated blood AFP levels. New, non
      AFP markers are thus needed, especially for small HCCs.

PMID- 29568492
TI  - Using regulatory genomics data to interpret the function of disease variants and
      prioritise genes from expression studies.
AB  - The identification of therapeutic targets is a critical step in the research and
      developement of new drugs, with several drug discovery programmes failing because
      of a weak linkage between target and disease. Genome-wide association studies and
      large-scale gene expression experiments are providing insights into the biology
      of several common diseases, but the complexity of transcriptional regulation
      mechanisms often limits our understanding of how genetic variation can influence
      changes in gene expression. Several initiatives in the field of regulatory
      genomics are aiming to close this gap by systematically identifying and
      cataloguing regulatory elements such as promoters and enhacers across different
      tissues and cell types. In this Bioconductor workflow, we will explore how
      different types of regulatory genomic data can be used for the functional
      interpretation of disease-associated variants and for the prioritisation of gene
      lists from gene expression experiments.

PMID- 29576868
TI  - A rare cause of primary adrenal insufficiency due to a homozygous Arg188Cys
      mutation in the STAR gene.
AB  - : Steroidogenic acute regulatory protein (STAR) is a key protein for the
      intracellular transport of cholesterol to the mitochondrium in endocrine organs
      (e.g. adrenal gland, ovaries, testes) and essential for the synthesis of all
      steroid hormones. Several mutations have been described and the clinical
      phenotype varies strongly and may be grouped into classic lipoid congenital
      adrenal hyperplasia (LCAH), in which all steroidogenesis is disrupted, and non
      classic LCAH, which resembles familial glucocorticoid deficiency (FGD), which
      affects predominantly adrenal functions. Classic LCAH is characterized by early
      and potentially life-threatening manifestation of primary adrenal insufficiency
      (PAI) with electrolyte disturbances and 46,XY disorder of sex development (DSD)
      in males as well as lack of pubertal development in both sexes. Non-classic LCAH
      manifests usually later in life with PAI. Nevertheless, life-long follow-up of
      gonadal function is warranted. We describe a 26-year-old female patient who was
      diagnosed with PAI early in life without detailed diagnostic work-up. At the age
      of 14 months, she presented with hyperpigmentation, elevated ACTH and low
      cortisol levels. As her older brother was diagnosed with PAI two years earlier,
      she was put on hydrocortisone and fludrocortisone replacement therapy before an
      Addisonian crisis occurred. Upon review of her case in adulthood, consanguinity
      was noted in the family. Genetic analysis for PAI revealed a homozygous mutation
      in the STAR gene (c.562C>T, p.Arg188Cys) in both siblings. This mutation has been
      previously described in non-classic LCAH. This case illustrates that early onset,
      familial PAI is likely due to autosomal recessive genetic mutations in known
      genes causing PAI. Learning points: In childhood-onset PAI, a genetic cause is
      most likely, especially in families with consanguinity.Adult patients with an
      etiologically unsolved PAI should be reviewed repeatedly and genetic work-up
      should be considered.Knowing the exact genetic diagnosis in PAI is essential for
      genetic counselling and may allow disease-specific treatment.Young men and women
      with NCLAH due to homozygous STAR Arg188Cys mutation should be investigated for
      their gonadal function as hypogonadism and infertility might occur during puberty
      or in early adulthood.

PMID- 29576869
TI  - Low carbohydrate diet and improved glycaemic control in a patient with type one
      diabetes.
AB  - : We present the case of an adult female with type 1 diabetes, whose HbA1c was
      trending at 58 mmol/mol (7.5%) for the past 3 years. In August 2016, she reduced
      her total daily carbohydrate intake to 30-50 g and adjusted her other
      macronutrients to compensate for the calorific deficit. Her HbA1c fell to 34
      mmol/mol (5.3%) by January 2017 and average daily blood glucose readings
      decreased significantly from 10.4 to 6.1 mmol/L. Moreover, she observed a marked
      reduction of average daily glucose variability. Notably, there were no
      significant episodes of hypo- or hyperglycaemia and her lipid profile remained
      static. Subjectively, she described an improvement in her quality of life and the
      dietary transition was extremely well tolerated. We discuss these findings in
      detail and the potential clinical benefits for patients with type 1 diabetes that
      can be gained by following a low carbohydrate diet. Learning points: A low
      carbohydrate diet was found to substantially reduce HbA1c values and blood
      glucose (BG) variability, as well as causing a significant reduction in average
      daily glucose values in a patient with T1DM.Although further research is
      warranted, low carbohydrate diets in patients with T1DM have the potential to
      positively impact long-term morbidity and mortality through reduction of BG
      variability and average daily BG values.The diet was well tolerated and not
      associated with any adverse effects within this study.

PMID- 29576870
TI  - Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis.
AB  - : Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which
      acts as immune checkpoint inhibitor against the programmed cell death protein-1,
      for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital
      critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as
      evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95
      and bicarbonate of 6.6 mmol/L. She has had no personal or family history of
      diabetes mellitus (DM), while random venous glucose, measured 1 week prior to
      hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD
      antibodies were 12 kIU/L (0-5 kU/L), while islet cell antibodies and serum C
      peptide were undetectable. Nivolumab was recommenced without the development of
      other immune-mediated phenomena until 6 months later, when she developed
      hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and
      has required levothyroxine replacement, while she has maintained good
      radiological and clinical response to immunotherapy. This case is notable for the
      rapidity of onset and profound nature of DKA at presentation, which occurred two
      months following commencement of immunotherapy. Despite the association of
      nivolumab with immune-mediated endocrinopathies, only a very small number of
      patients developing type 1 DM has been reported to date. Patients should be
      closely monitored for hyperglycaemia and thyroid dysfunction prior to and
      periodically during immunotherapy. Learning points: Nivolumab can induce
      fulminant type 1 diabetes, resulting in DKA.Nivolumab is frequently associated
      with thyroid dysfunction, mostly hypothyroidism.Nivolumab-treated patients should
      be monitored regularly for hyperglycaemia and thyroid dysfunction.Clinicians
      should be aware and warn patients of potential signs and symptoms of severe
      hyperglycaemia.

PMID- 29576871
TI  - De novo HNF1 homeobox B mutation as a cause for chronic, treatment-resistant
      hypomagnesaemia.
AB  - : 29-year-old female presenting with an 8-year history of unexplained
      hypomagnesaemia, which was severe enough to warrant intermittent inpatient
      admission for intravenous magnesium. Urinary magnesium was inappropriately normal
      in the context of hypomagnesaemia indicating magnesium wasting. Ultrasound
      imaging demonstrated unilateral renal cysts and computed tomography of kidneys,
      ureters and bladder showed a bicornuate uterus. Referral to genetic services and
      subsequent testing revealed a de novo HNF1B deletion. Learning points: HNF1B loss
      of-function mutations are one of the most common monogenic causes of congenital
      anomalies of the kidney and urinary tract.Those with HNF1B mutations may have
      some of a constellation of features (renal and hepatic cysts, deranged liver
      function tests, maturity onset diabetes of the young type 5 (MODY5), bicornuate
      uterus, hyperparathyroidism, hyperuricaemic gout, but presenting features are
      highly heterogeneous amongst patients and no genotype/phenotype correlation
      exists. HNF1B mutations are inherited in an autosomal dominant pattern but up to
      50% of cases are de novo.HNF1B mutations can be part of the Chr17q12 deletion
      syndrome, a contiguous gene deletion syndrome.Inorganic oral magnesium
      replacements are generally poorly tolerated with side effects of diarrhoea.
      Organic magnesium compounds, such as magnesium aspartate, are better absorbed
      oral replacement therapies.

PMID- 29576872
TI  - PFO closure in high-risk patient with paradoxical arterial embolism, deep vein
      thrombosis, pulmonary embolism and factor V Leiden genetic mutation.
AB  - Occurrence of paradoxical arterial embolism may cause the first symptoms in
      patients with a coexisting hypercoagulable state and patent foramen ovale (PFO).
      This can result in significant morbidity and mortality depending on the location
      of the embolism. The risks and benefits of closure of small PFOs have not been
      well elucidated in prior studies. We describe a patient with a history of Factor
      V Leiden heterozygosity who presented with left arm pain secondary to arterial
      embolism. The patient was a 51-year-old male who initially presented to the
      emergency department after awaking from sleep with progressive, severe, burning
      left arm pain. He had also noted intermittent shortness of breath over the 2
      weeks prior to admission. Temperature was 97.4 F, pulse 86, respiratory rate 20
      and blood pressure 121/87. Oxygen saturation was 94% on supplemental oxygen. He
      had a cool left upper extremity and the patient described subjective paresthesias
      in this extremity. Left radial pulse was difficult to palpate. Physical exam was
      otherwise unremarkable. Troponin I was mildly elevated at 0.217 ng/l. White blood
      cell count was 11.8 and INR 1.1. EKG showed sinus tachycardia with non-specific T
      abnormalities in the anterior leads. His past medical history was notable for
      only hypertension and hyperlipidemia. Current recommendation is for antiplatelet
      or anticoagulation for those with hypercoaguable states who suffer a stroke;
      there is currently no absolute indication for closure device. We describe the
      case of a 51-year-old male who had presented with left arm pain and shortness of
      breath. The computed tomography (CT) angiography of chest showed pulmonary emboli
      with heavy clot burden bilaterally. Heparin was started, but patient was found to
      have occlusion along large arteries of the left arm. Emergent left axillary,
      brachial, radial and ulnar embolectomy for acute critical arm ischemia were
      performed. The transthoracic echocardiogram done the next day with bubble study
      was positive for patent foramen ovale. Hypercoaguability showed factor V Leiden
      heterozygosity. Decision was made for the patient to initiate long-term
      anticoagulation with rivaroxaban and closure was performed. Patient was advised
      that closure is off label but opted to proceed with closure in light of
      hypercoaguable state.

PMID- 29576873
TI  - Systematic review of innovation design contests for health: spurring innovation
      and mass engagement.
AB  - We undertook a systematic review evaluating the effectiveness and cost of health
      focused innovation design contests. We followed Cochrane guidance and
      systematically searched eight databases. Articles were included if they reported
      an open contest focused on improving health, required participants submit
      finished design solutions and contained a prize structure. We searched 3579
      citations, identifying 29 health-focused innovation design contests which
      collectively received 15494 contest submissions. Contests solicited submissions
      worldwide (7) and exclusively from North America (13), Asia (4), Africa (2),
      Australia (2) and Europe (1). Submissions per contest ranged from 3 to 11354
      (median of 73). Contest entrants were tasked with helping develop health
      promotion messages (HPM) (25) and improve predictive clinical models, protocols
      and/or algorithms (4). Two types of contests emerged-those focused on high
      quality, innovative outcomes and those focused on the process of mass community
      engagement. All outcome-oriented contests had innovation design contest solutions
      equivalent or superior to the comparator (100%; 7/7). Two of two studies found
      that innovation design contests saved money (100%; 2/2). Five of seven process
      oriented contests concluded the contest improved at least one health indicator
      (71%; 5/7). Innovation design contests are an effective way to solicit innovative
      solutions to health problems and spur mass community engagement.

PMID- 29576874
TI  - Self-government of complex reading and writing brains informed by cingulo
      opercular network for adaptive control and working memory components for language
      learning.
AB  - To understand mental self-government of the developing reading and writing brain,
      correlations of clustering coefficients on fMRI reading or writing tasks with
      BASC 2 Adaptivity ratings (time 1 only) or working memory components (time 1
      before and time 2 after instruction previously shown to improve achievement and
      change magnitude of fMRI connectivity) were investigated in 39 students in grades
      4 to 9 who varied along a continuum of reading and writing skills. A Philips 3T
      scanner measured connectivity during six leveled fMRI reading tasks (subword
      letters and sounds, word-word-specific spellings or affixed words, syntax
      comprehension-with and without homonym foils or with and without affix foils, and
      text comprehension) and three fMRI writing tasks-writing next letter in alphabet,
      adding missing letter in word spelling, and planning for composing. The Brain
      Connectivity Toolbox generated clustering coefficients based on the cingulo
      opercular (CO) network; after controlling for multiple comparisons and movement,
      significant fMRI connectivity clustering coefficients for CO were identified in 8
      brain regions bilaterally (cingulate gyrus, superior frontal gyrus, middle
      frontal gyrus, inferior frontal gyrus, superior temporal gyrus, insula, cingulum
      cingulate gyrus, and cingulum-hippocampus). BASC2 Parent Ratings for Adaptivity
      were correlated with CO clustering coefficients on three reading tasks (letter
      sound, word affix judgments and sentence comprehension) and one writing task
      (writing next letter in alphabet). Before instruction, each behavioral working
      memory measure (phonology, orthography, morphology, and syntax coding,
      phonological and orthographic loops for integrating internal language and output
      codes, and supervisory focused and switching attention) correlated significantly
      with at least one CO clustering coefficient. After instruction, the patterning of
      correlations changed with new correlations emerging. Results show that the
      reading and writing brain's mental government, supported by both CO Adaptive
      Control and multiple working memory components, had changed in response to
      instruction during middle childhood/early adolescence.

PMID- 29576876
TI  - Corneal Biomechanical Properties after FS-LASIK with Residual Bed Thickness Less
      Than 50% of the Original Corneal Thickness.
AB  - Background: The changes in corneal biomechanical properties after LASIK remain an
      unknown but important topic for surgical design and prognostic evaluation. This
      study aims to observe the postoperative corneal biomechanical properties one
      month after LASIK with amount of corneal cutting (ACC) greater than 50% of the
      central corneal thickness (CCT). Methods: FS-LASIK was performed in 10 left
      rabbit eyes with ACC being 60% (L60) and 65% (L65) of the CCT, while the right
      eyes (R) were the control. After 4 weeks, rabbits were executed and corneal strip
      samples were prepared for uniaxial tensile tests. Results: At the same strain,
      the stresses of L65 and L60 were larger than those of R. The elastic moduli of
      L60 and L65 were larger than those of R when the stress was 0.02 MPa, while they
      began to be less than those of R when stress exceeds the low-stress region. After
      10 s relaxation, the stress of specimens L65, L60, and R increased in turn.
      Conclusion: The elastic moduli of the cornea after FS-LASIK with ACC greater than
      50% of the CCT do not become less under normal rabbit IOP. The limit stress grows
      with the rise of ACC when relaxation becomes stable.

PMID- 29576877
TI  - Effect of Hemodialysis on Eye Coats, Axial Length, and Ocular Perfusion Pressure
      in Patients with Chronic Renal Failure.
AB  - Purpose: To investigate changes in eye coats, axial length, and ocular perfusion
      pressure (OPP) in hemodialysis (HD) patients with chronic renal failure (CRF).
      Methods: We included HD patients who were diagnosed with CRF in our hospital from
      January to December 2015. Fifty-two patients met the inclusion criteria; all
      right eyes were used for observation. Systolic and diastolic blood pressures were
      recorded to calculate OPP. Approximately 30 minutes before and after HD, we
      recorded multiple parameters, including lens thickness (LT), axial length of
      vitreous (VAL), axial length of eye (EAL), ciliary body thickness (CBT),
      choroidal thickness (CT), and retinal thickness (RT). Results: After HD, OPP
      significantly decreased (P < 0.01, F = 7.023) and CBT became significantly
      thinner (P < 0.01, t = 3.461). CT was significantly thinner and differed among
      measurement locations (P < 0.01, t = 6.240; P < 0.01, t = 6.169; P < 0.01, t =
      3.405, respectively, fovea, nasal, and temporal side 1500 MUm beside the fovea).
      Further, RT thickened and differed among measurement locations (P < 0.05, t = 
      2.265; P < 0.05, t = -2.624; P < 0.05, t = -2.220, respectively, fovea, nasal,
      and temporal side 1500 MUm beside fovea), whereas LT, VAL, and EAL significantly
      increased after HD (P < 0.05, t = -2.076; P < 0.01, t = -3.817; P < 0.01, t = 
      4.010). Conclusions: HD impacts the thickness of the eye coats and VAL,
      particularly affecting CBT, CT, and RT. OPP transiently decreases during HD,
      which may contribute to an ischemic state.

PMID- 29576875
TI  - Current Advances in Pharmacotherapy and Technology for Diabetic Retinopathy: A
      Systematic Review.
AB  - Diabetic retinopathy (DR) is classically defined by its vascular lesions and
      damage in the neurons of the retina. The cellular and clinical elements of DR
      have many features of chronic inflammation. Understanding the individual cell
      specific inflammatory changes in the retina may lead to novel therapeutic
      approaches to prevent vision loss. The systematic use of available
      pharmacotherapy has been reported as a useful adjunct tool to laser
      photocoagulation, a gold standard therapy for DR. Direct injections or
      intravitreal anti-inflammatory and antiangiogenesis agents are widely used
      pharmacotherapy to effectively treat DR and diabetic macular edema (DME).
      However, their effectiveness is short term, and the delivery system is often
      associated with adverse effects, such as cataract and increased intraocular
      pressure. Further, systemic agents (particularly hypoglycemic, hypolipidemic, and
      antihypertensive agents) and plants-based drugs have also provided promising
      treatment in the progression of DR. Recently, advancements in pluripotent stem
      cells technology enable restoration of retinal functionalities after
      transplantation of these cells into animals with retinal degeneration. This
      review paper summarizes the developments in the current and potential
      pharmacotherapy and therapeutic technology of DR. Literature search was done on
      online databases, PubMed, Google Scholar, clinitrials.gov, and browsing through
      individual ophthalmology journals and leading pharmaceutical company websites.

PMID- 29576879
TI  - The Balance of Th1/Th2 and LAP+Tregs/Th17 Cells Is Crucial for Graft Survival in
      Allogeneic Corneal Transplantation.
AB  - Purpose: CD4+LAP+ T cells are newly discovered regulatory T cells (Tregs). The
      aim of this study is to investigate the balance of Th1/Th2 and LAP+Tregs/Th17 in
      mice after allogeneic corneal transplantation. Methods: A total of 65 mice
      received orthotopic penetrating transplantation. According to the survival scores
      of the grafts, the mice were divided into the rejection group and the survival
      group 3 weeks after transplantation. Th1, Th2, Th17, and regulatory T cells in
      the ipsilateral drainage lymph nodes and spleens were measured with flow
      cytometry. The related cytokines in aqueous humor were also analyzed. Results:
      The frequencies of Foxp3+Tregs, GARP+Tregs, and LAP+Tregs in the survival group
      were significantly higher than those in the rejection group. And the expression
      trend of CD4+LAP+ T cells and CD4+GARP+ T cells was consistent. The level of IFN
      gamma, TNF, IL-6, and IL-17A markedly increased in aqueous humor during corneal
      allograft rejection. The ratio of Th1/Th2 and Th17/LAP+Tregs significantly
      increased in the rejection group at the 3rd week after corneal transplantation.
      Conclusion: LAP+Tregs might be regarded as substitute for Foxp3+Tregs. The
      balance of Th1/Th2 and LAP+Tregs/Th17 is crucial for corneal allograft survival.

PMID- 29576878
TI  - Early Intervention and Nonpharmacological Therapy of Myopia in Young Adults.
AB  - Myopia is a condition of the eye where parallel rays focus in front of, instead
      of on, the retina, which results in excessive refractive power of the cornea or
      the lens or eyeball elongation. Studies carried out in recent years show that the
      etiology of myopia is complex with genetic and environmental factors playing a
      role. Refraction defects decrease the quality of vision, while progressing myopia
      can lead to partial loss of vision, which can be particularly dramatic in young
      adults. Therefore, it is so crucial to take appropriate actions aimed at
      preventing myopia progression. This is a review of nonpharmacological therapeutic
      possibilities of refraction defect prevention in young adults, with special
      regard to myofascial therapy, osteopathy, and massage of acupuncture points
      surrounding the eye.

PMID- 29576880
TI  - Three-Year Outcomes of Cross-Linking PLUS (Combined Cross-Linking with
      Femtosecond Laser Intracorneal Ring Segments Implantation) for Management of
      Keratoconus.
AB  - Purpose: To analyze the results of three-year outcomes of combined epithelium-on
      cross-linking with femtosecond laser ICRS (cross-linking PLUS) for keratoconus
      management. Design: A retrospective multicenter clinical study. Methods: 43 eyes
      of 38 patients were subjected to preoperative and postoperative UCVA, BCVA,
      refraction, Pentacam pachymetry, and keratometry examinations at 3-, 6-, 12-, 24
      , and 36-month follow-up period. Results: The preoperative and postoperative mean
      UCVA was 1.30 +/- 0.48 (logMAR +/- SD) and 0.82 +/- 0.22 respectively. The
      preoperative and postoperative mean BCVA was 0.90 +/- 0.40 and 0.60 +/- 0.30,
      respectively. The preoperative and postoperative mean K average was 50.63 +/-
      0.87 (D +/- SD) and 45.56 +/- 0.98, respectively. The preoperative and
      postoperative mean pachymetry was 471 +/- 92.36 (MUm +/- SD) and 423 +/- 39.58,
      respectively. The preoperative and postoperative mean astigmatism was 7.55 +/-
      1.75 and 3.39 +/- 1.26, respectively. One eye showed ICRS edge exposure while 6
      eyes showed progression of keratoconus. Conclusion: CXL PLUS was proved to be a
      successful procedure to halt progression (mainly by CXL) and to correct the
      refractive status of the keratoconic eye (mainly by ICRS). CXL PLUS performed a
      synergistic action correcting and maintaining the correction of both myopic and
      astigmatic components of keratoconus.

PMID- 29576881
TI  - Combined Phacoemulsification and Goniosynechialysis under an Endoscope for
      Chronic Primary Angle-Closure Glaucoma.
AB  - Purpose: To investigate the clinical efficacy and safety of combined
      phacoemulsification with goniosynechialysis (GSL) under an ophthalmic endoscope
      for chronic primary angle-closure glaucoma and coexisting cataract. Methods: This
      is a retrospective study. The intraocular pressure (IOP), best-corrected visual
      acuity (BCVA), and number of glaucoma medications at baseline and each
      postoperative follow-up visit were recorded. Other measurements included
      supraciliochoroidal fluid measured by anterior segment optical coherence
      tomography, corneal endothelial cell density (ECD), and peripheral anterior
      synechia (PAS). All patients were followed for more than a year. Results: Thirty
      eight eyes of 31 patients were included. The mean follow-up duration was 16.3 +/-
      3.9 months. The IOP decreased from 22.2 +/- 9.3 mmHg at baseline to 15.4 +/- 4.2
      mmHg at the last follow-up (P < 0.001). The mean number of glaucoma medications
      (0.1 +/- 0.6) at the last follow-up was significantly lower than the preoperative
      number (2.3 +/- 1.1) (P < 0.001). All patients achieved improved or stable visual
      acuity after surgery. All patients achieved a complete opened angle after GSL.
      The postoperative complications included hyphema (7.9%), exudation (5.3%),
      transiently elevated IOP (55.3%), and supraciliochoroidal fluid (40%).
      Conclusions: Combined phacoemulsification and GSL under an endoscope can
      completely reopen PAS and is an effective and safe method for patients with
      chronic primary angle-closure glaucoma and coexisting cataract.

PMID- 29576882
TI  - Effect of Atropine Eye Drops on Choroidal Thinning Induced by Hyperopic Retinal
      Defocus.
AB  - Purpose: To investigate the effects of atropine on choroidal thinning induced by
      hyperopic retinal defocus. Methods: Ten young adults with myopia (-1.00 D to 
      5.00 D) viewed a video at 6 metres for 60 minutes on successive days. On day 1,
      one eye (control) was distance corrected with a contact lens; the other
      (experimental) eye wore a contact lens imposing 2.00 D of hyperopic retinal
      defocus. Sub- and perifoveal choroidal thickness (SFCT, PFCT) were monitored with
      optical coherence tomography. On day 2, the procedure was repeated but the
      experimental eye had received one drop of 0.5% atropine 22 hours earlier.
      Results: On day 1, eyes exposed to hyperopic defocus developed progressively
      thinner choroids (SFCT (baseline) = 253 +/- 32 MUm versus SFCT (40 mins) = 244 +/
      31 MUm, p = 0.004), whereas SFCT and PFCT in control eyes did not change (p >
      0.17). On day 2 (22 hours after instilling atropine), baseline SFCT and PFCT were
      not different to day 1 (p > 0.05) and hyperopic defocus failed to thin the
      choroid (max change in SFCT = +2 +/- 2 MUm, p = 0.36). Conclusions: Atropine
      abolished choroidal thinning induced by hyperopic defocus without changing
      baseline choroidal thickness. The results suggest that atropine inhibits signals
      associated with hyperopic defocus, for example, from lag of accommodation during
      near work. This trial is registered with ACTRN12617001519347.

PMID- 29576883
TI  - Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast
      Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor
      Vaccine.
AB  - Introduction: No effective treatment has been developed for bone-metastatic
      breast cancer. We found 3 cases with clinical complete response (cCR) of the bone
      metastasis and longer overall survival of the retrospectively examined cohort
      treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV).
      Patients and Methods: AFTV was prepared individually for each patient from their
      own formalin-fixed and paraffin-embedded breast cancer tissues. Results: Three
      patients maintained cCR status of the bone metastasis for 17 months or more. Rate
      of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive
      treatments including AFTV. The median overall survival time (60.0 months) and the
      3- to 8-year survival rates after diagnosis of bone metastasis were greater than
      those of historical control cohorts in Japan (1988-2002) and in the nationwide
      population-based cohort study of Denmark (1999-2007). Conclusion: Bone-metastatic
      breast cancer may be curable after comprehensive treatments including AFTV,
      although larger scale clinical trial is required.

PMID- 29576884
TI  - Corrigendum to "Nonfamilial Juvenile Polyposis Syndrome with Exon 5 Novel
      Mutation in SMAD 4 Gene".
AB  - [This corrects the article DOI: 10.1155/2017/5321860.].

PMID- 29576885
TI  - Revising Reverse-Phase Chromatographic Behavior for Efficient Differentiation of
      Both Positional and Geometrical Isomers of Dicaffeoylquinic Acids.
AB  - Dicaffeoylquinic acids (diCQAs) are plant metabolites and undergo trans-cis
      isomerization when exposed to UV irradiation. As such, diCQAs exist in both trans
      and cis-configurations and amplify the already complex plant metabolome.
      However, analytical differentiation of these geometrical isomers using mass
      spectrometry (MS) approaches has proven to be extremely challenging. Exploring
      the chromatographic space to develop possible conditions that would aid in
      differentially separating and determining the elution order of these isomers is
      therefore imperative. In this study, simple chromatographic parameters, such as
      column chemistry (phenyl versus alkyl), mobile phase composition (methanol or
      acetonitrile), and column temperature, were investigated to aid in the separation
      of diCQA geometrical isomers. The high-performance liquid chromatography
      photodiode array (HPLC-PDA) chromatograms revealed four isomers post UV
      irradiation of diCQA authentic standards. The elution profile/order was seen to
      vary on different reverse-phase column chemistries (phenyl versus alkyl) using
      different mobile phase composition. Here, the elution profile/order on the phenyl
      derived column matrices (with methanol as the mobile phase composition) was
      observed to be relatively reproducible as compared to the alkyl (C18) columns.
      Chromatographic resolution of diCQA geometrical isomers can be enhanced with an
      increase in column temperature. Lastly, the study highlights that chromatographic
      elution order/profile cannot be relied upon to fathom the complexity of isomeric
      plant metabolites.

PMID- 29576886
TI  - A Localized Surface Plasmon Resonance Sensing Method for Simultaneous
      Determination of Atenolol and Amiloride in Pharmaceutical Dosage Forms and Urine
      Samples.
AB  - This contribution describes a simple, fast, and sensitive application of
      localized surface plasmon resonance effect of silver nanoparticles for
      simultaneous determination of antihypertensive drugs' mixture atenolol and
      amiloride in both pharmaceutical dosage forms and in biological samples (urine).
      Silver nanoparticles were prepared by chemical reduction of silver nitrate using
      hydroxylamine HCL in an alkaline medium. Application of silver-hydroxylamine
      nanoparticles (SH NPs) provides many advantages including reproducibility,
      sensitivity, and cost effective way of analyte determination. Amiloride has four
      amino groups which act as attachment points on the surface of silver
      nanoparticles resulting in a synergistic effect on the absorption intensity of
      atenolol, leading to increase the sensitivity of the determination of both
      compounds. This method shows excellent advantages comparing with the previously
      reported methods, including accuracy, precision, and selectivity. The linear
      range of atenolol is 1 * 10-5-1 * 10-4 mol.L-1 and of amiloride is 1 * 10-6-1 *
      10-5 mol.L-1. The limit of detection (LOD) values of atenolol and amiloride are
      0.89 * 10-5 and 0.42 * 10-6 mol.L-1, respectively.

PMID- 29576887
TI  - Two-color multiphoton in vivo imaging with a femtosecond diamond Raman laser.
AB  - Two-color multiphoton microscopy through wavelength mixing of synchronized lasers
      has been shown to increase the spectral window of excitable fluorophores without
      the need for wavelength tuning. However, most currently available dual output
      laser sources rely on the costly and complicated optical parametric generation
      approach. In this report, we detail a relatively simple and low cost diamond
      Raman laser pumped by a ytterbium fiber amplifier emitting at 1055 nm, which
      generates a first Stokes emission centered at 1240 nm with a pulse width of 100
      fs. The two excitation wavelengths of 1055 and 1240 nm, along with the effective
      two-color excitation wavelength of 1140 nm, provide an almost complete coverage
      of fluorophores excitable within the range of 1000-1300 nm. When compared with
      1055 nm excitation, two-color excitation at 1140 nm offers a 90% increase in
      signal for many far-red emitting fluorescent proteins (for example, tdKatushka2).
      We demonstrate multicolor imaging of tdKa-tushka2 and Hoechst 33342 via
      simultaneous two-color two-photon, and two-color three-photon microscopy in
      engineered 3D multicellular spheroids. We further discuss potential benefits and
      applications for two-color three-photon excitation. In addition, we show that
      this laser system is capable of in vivo imaging in mouse cortex to nearly 1 mm in
      depth with two-color excitation.

PMID- 29576888
TI  - Long Non-coding RNA in Liver Metabolism and Disease: Current Status.
AB  - Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200
      nucleotides in length but lacking identifiable open reading frames (with rare
      exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs
      are critical regulators of liver metabolic function and diseases. We summarize
      current knowledges about dysregulated lncRNAs and outline the underlying
      molecular mechanisms by which lncRNAs control hepatic lipid ad glucose
      metabolism, as well as cholestatic liver disease. lncLSTR, Lnc18q22.2, SRA, HULC,
      MALAT1, lncLGR, MEG3, and H19, lncHR1, lnc-HC, APOA1-AS, DYNLRB2-2, and LeXis are
      included in the discussion.

PMID- 29576889
TI  - Recent development and gene therapy for glycogen storage disease type Ia.
AB  - Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive metabolic
      disorder caused by a deficiency in glucose-6-phosphatase-alpha (G6Pase-alpha or
      G6PC) that is expressed primarily in the liver, kidney, and intestine. G6Pase
      alpha catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and
      phosphate in the terminal step of gluconeogenesis and glycogenolysis, and is a
      key enzyme for endogenous glucose production. The active site of G6Pase-alpha is
      inside the endoplasmic reticulum (ER) lumen. For catalysis, the substrate G6P
      must be translocated from the cytoplasm into the ER lumen by a G6P transporter
      (G6PT). The functional coupling of G6Pase-alpha and G6PT maintains interprandial
      glucose homeostasis. Dietary therapies for GSD-Ia are available, but cannot
      prevent the long-term complication of hepatocellular adenoma that may undergo
      malignant transformation to hepatocellular carcinoma. Animal models of GSD-Ia are
      now available and are being exploited to both delineate the disease more
      precisely and develop new treatment approaches, including gene therapy.

PMID- 29576890
TI  - Long-term Results in Pediatric Developmental Cataract Surgery with Primary
      Intraocular Lens Implantation.
AB  - Objectives: The aim of this study was to evaluate the outcomes of pediatric
      developmental cataract surgery with primary intraocular lens (IOL) implantation.
      Materials and Methods: Patients between 2 and 16 years old who underwent cataract
      surgery with primary IOL implantation were retrospectively evaluated. Age at time
      of surgery, pre- and postoperative best corrected visual acuities, postoperative
      ocular complications, and any accompanying ocular pathologies were obtained from
      the patients' charts. Mean refractive changes and degree of myopic shift were
      analyzed according to the age groups. Operated eyes were also compared with the
      fellow eyes in unilateral cases. Results: A total of 101 eyes of 65 patients were
      included. The average age at time of surgery was 76+/-40 months and the average
      follow-up period was 44+/-30 months. Among the 78 eyes that could be assessed for
      visual acuity improvement, 66 (84.6%) of them showed >=2 lines of improvement.
      The difference in the mean refractive change between the 2-5 years old and 8-16
      years old age groups was found to be statistically significant. However, the mean
      refractive change per year was not found to be significant between the same age
      groups. In unilateral cases, the operated eyes showed a greater myopic change
      than the fellow eyes, with no statistically significant difference. The most
      common postoperative complication was visual axis opacity. Conclusion: Good
      visual outcomes can be achieved following pediatric cataract surgery with primary
      IOL implantation. Optic axis opacities were the most common postoperative
      complications. Overall, refractive changes following surgery are inevitable, and
      more prominent in younger age groups.

PMID- 29576891
TI  - Visual Results Following Implantation of a Refractive Multifocal Intraocular Lens
      in One Eye and a Diffractive in the Contralateral Eye.
AB  - Objectives: To assess the visual outcomes in patients who underwent cataract
      surgery with multifocal intraocular lens (IOL) implantation using a "mix and
      match" approach. Materials and Methods: Twenty patients (40 eyes) were involved
      in this prospective, nonrandomized study. Refractive multifocal IOLs (ReZoom
      NXG1) were implanted in patients' dominant eyes and diffractive multifocal IOLs
      (Tecnis ZMA00) were implanted in their non-dominant eyes. Monocular and binocular
      uncorrected distance, intermediate and near visual acuity (logMAR), and contrast
      sensitivity levels were measured at 1, 3, and 6 months after cataract surgery.
      Defocus curves, reading speeds, patient satisfaction, spectacle dependence, and
      halo and glare symptoms were also evaluated at 6 months after the surgery.
      Postoperative quality of life was assessed with the Turkish version of National
      Eye Institute Visual Function Questionnaire-25. Results: The study group
      comprised 8 females and 12 males with a mean age of 69.45+/-10.76 years (range,
      31-86 years). The uncorrected distance and intermediate visual acuity levels were
      significantly better in the ReZoom-implanted eyes at postoperative 6 months
      (p=0.026 and p=0.037, respectively). There was no statistically significant
      difference in uncorrected near visual acuity (p>0.05). There was no statistically
      significant difference in contrast sensitivity, reading speed, halos, or glare
      between the groups (p<0.05). Mild glare/halo was reported by 40% of the subjects.
      The mean patient satisfaction was 95% and all patients were spectacle
      independent. Conclusion: Mixing and matching multifocal IOLs in selected cataract
      patients provides excellent visual outcome, a high level of patient satisfaction,
      and spectacle independency.

PMID- 29576892
TI  - Amniotic Membrane Transplantation in Surgical Treatment of Conjunctival Melanoma:
      Long-term Results.
AB  - Objectives: To investigate the long-term efficacy and results of surgical
      management of conjunctival melanoma reconstructed with amniotic membrane
      transplantation. Materials and Methods: Conjunctival melanoma in 10 patients (5
      female, 5 male) was totally excised with adjunctive cryotherapy to the surgical
      margins, corneal epitheliectomy with absolute alcohol in cases of corneal
      involvement, lamellar sclerectomy in cases with episcleral involvement, and
      ocular surface grafting with cryopreserved amniotic membrane. Complications and
      tumor control rates were evaluated. Results: The mean age of the patients was
      57.4+/-15.2 (range, 37-84) years. The mean diameter of the tumors was 15.5+/-4.9
      (range, 10-25) mm and histopathologically confirmed complete excision was
      performed in all cases. Mild limbal stem cell deficiency (2 eyes) and subclinical
      symblepharon (3 eyes) were observed as long-term complications. In a mean follow
      up of 56.7+/-40.4 (range, 30-132) months, only one local tumor recurrence was
      detected. Despite retreatment, exenteration was performed in this patient due to
      re-recurrence. One patient died due to disseminated metastasis despite the
      absence of local recurrence. Conclusion: In large conjunctival melanomas,
      reconstruction of the ocular surface is usually very challenging. The use of
      cryopreserved amniotic membrane for conjunctival defect repair is safe and
      effective with mild complications, and allows the excision of wider margins
      around the tumor.

PMID- 29576893
TI  - The Profile and Management of Glaucoma in Adult Aphakic Patients Following
      Complicated Cataract Surgery.
AB  - Objectives: To determine the profile and clinical course of glaucoma in adult
      aphakic patients following complicated cataract surgery. Materials and Methods:
      Retrospective chart review of 22 adult aphakic patients (29 eyes) with glaucoma.
      Results: Mean age was 57.69+/-14.18 years when aphakia occurred. Mean age at time
      of presentation to our glaucoma clinic was 62.57+/-12.47 years. Mean follow-up
      time was 42.83+/-57.04 months. Changes between the first and last follow-up
      visits were as follows: mean intraocular pressure decreased from 26.21+/-13.86
      mmHg to 18.14+/-9.63 mmHg (p=0.003); mean number of glaucoma medications used
      increased from 1.41+/-1.27 to 2.07+/-1.04 (p=0.005); and mean vertical cup/disc
      ratio increased from 0.69+/-0.25 to 0.78+/-0.24 (p=0.024). Glaucoma was managed
      using medications in 26 eyes (89.7%), whereas 3 eyes underwent surgical
      treatment. However, surgery alone was not sufficient to control intraocular
      pressure and additional glaucoma medications were needed. Conclusion: Prevention
      of glaucomatous optic neuropathy in aphakic patients is challenging both
      medically and surgically. Although a significant decrease in intraocular pressure
      can be achieved with glaucoma medications, glaucomatous disc changes may
      progress.

PMID- 29576894
TI  - Characteristics of Anisometropic Patients with and without Strabismus.
AB  - Objectives: To evaluate the risk factors for strabismus in patients with
      anisometropia by comparing degree of anisometropia, depth of amblyopia, and
      binocular visual function in anisometropic patients with and without strabismus.
      Materials and Methods: Sixty-five anisometropic patients older than 5 years with
      amblyopia in one eye who were followed in the Ankara University Faculty of
      Medicine, Department of Ophthalmology, Pediatric Ophthalmology and Strabismus
      Unit between May 2009 and April 2010 were included in this study. There were 27
      cases of strabismus. The depth of amblyopia, degree of anisometropia, and
      binocular visual function were assessed in anisometropic cases with and without
      strabismus. Results: The 65 patients with anisometropia were divided into two
      groups: 27 patients with strabismus (group 1) and 38 patients without (group 2).
      Depth of amblyopia was greater in patients with strabismus compared to those
      without (p=0.006). In patients with strabismus, there was no correlation between
      angle of deviation and depth of amblyopia (p=0.453). In anisometropic amblyopia
      patients without strabismus, there was a positive correlation between depth of
      anisometropia and depth of amblyopia (p=0.35, Pearson's correlation
      coefficient=0.343). Comparison in terms of anisometropia showed that patients
      with strabismus had significantly larger spherical difference between the two
      eyes than in patients without strabismus (p=0.000, Mann-Whitney U test). There
      was no significant difference in terms of cylindrical values (p=0.146, Mann
      Whitney U test). There was no statistically significant difference in the
      presence of fusion between anisometropic patients with and without strabismus.
      Conclusion: The risk of developing strabismus increased as degree of
      anisometropia increased in anisometropic cases. In addition, depth of amblyopia
      was greater in anisometropic patients with strabismus.

PMID- 29576895
TI  - Direct Treatment Costs of Neovascular Age-related Macular Degeneration and
      Comparison of Gained and/or Preserved Vision with Expenditure.
AB  - Objectives: The aim was to quantify the direct medical cost of neovascular age
      related macular degeneration (AMD) versus gained or preserved vision. Materials
      and Methods: Data of patients treated for neovascular AMD between January 2009 to
      January 2014 were reviewed. Patients with complete follow-up for two years,
      treated with only intravitreal ranibizumab injections and with no intraocular
      surgery were included. Demographics, diagnostic investigations, the number of
      visits and injections, changes in visual acuity (VA) at one year and two years
      from baseline were noted. Total cost was calculated for the first and second
      years, and the cost of improving or preserving initial vision level was
      determined with subgroup analysis. Results: Two-hundred eyes of 175 patients (86
      male and 89 female) with a mean age of 72.3+/-7.8 years were included. Mean VA
      was 0.67 logMAR at baseline, 0.60 logMAR at the end of the first year, and 0.67
      logMAR at the end of the second year. At the end of the 2 years, VA increased in
      82 eyes (41%), remained the same in 42 eyes (21%), and decreased in 76 eyes
      (38%). The mean number of visits in the first and second years were 6.56 (3-12)
      and 5.74 (3-10), respectively. An average of 4.42 (1-8) injections were performed
      in the first year and 2.25 (0-7) in the second. The total direct medical cost for
      AMD was 9,628 TL (Turkish Lira) per patient for 2 years, which consisted of 529
      TL in visit costs, 115 TL in fluorescein and indocyanine angiography costs, 611
      TL in injection procedure costs, and 8,371 TL in drug costs. The cost of one line
      of VA gain was 11,911 TL in the first year. Conclusion: This study showed that
      treatment increased or stabilized vision in a reasonable proportion of patients,
      that cost of management decreases in the second year, and that drug expenses are
      the leading item in reimbursement.

PMID- 29576896
TI  - Stem Cell Treatment in Retinal Diseases: Recent Developments.
AB  - Stem cells are undifferentiated cells which have the ability to self-renew and
      differentiate into mature cells. They are highly proliferative, implying that an
      unlimited number of mature cells can be generated from a given stem cell source.
      On this basis, stem cell replacement therapy has been evaluated in recent years
      as an alternative for various pathologies. Degenerative retinal diseases cause
      progressive visual decline which originates from continuing loss of photoreceptor
      cells and outer nuclear layers. Theoretically, this therapy will enable the
      generation of new retinal cells from stem cells to replace the damaged cells in
      the diseased retina. In addition, stem cells are able to perform multiple
      functions, such as immunoregulation, anti-apoptosis of neurons, and neurotrophin
      secretion. With recent progress in experimental stem cell applications, phase
      I/II clinical trials have been approved. These latest stem cell transplantation
      studies showed that this therapy is a promising approach to restore visual
      function in eyes with degenerative retinal diseases such as retinitis pigmentosa,
      Stargardts' macular dystrophy, and age-related macular degeneration. This review
      focuses on new developments in stem cell therapy for degenerative retinal
      diseases.

PMID- 29576897
TI  - Primary Conjunctival Tuberculosis.
AB  - A 12-year-old girl was referred to our clinic because of unilateral
      conjunctivitis not responding to treatment. In the left eye, lower bulbar and
      tarsal conjunctiva had a polypoidal appearance due to micronodules and there was
      a subconjunctival nodular mass in the inferior fornix. Systemic examination was
      unremarkable except for a left preauricular lymphadenopathy. Excision biopsy of
      the subconjunctival mass revealed a granulomatous inflammation with caseation
      necrosis, but acid-fast bacilli (AFB) was negative. Fine needle-aspiration biopsy
      of the preauricular lymph node was performed. In microbiological examination,
      both AFB and mycobacterial culture were positive. The isolated mycobacteria
      strains were identified as Mycobacterium tuberculosis complex and full remission
      was achieved with 6 months of anti-tuberculosis treatment. Although primary
      tuberculous conjunctivitis is a very rare condition, it should be considered in
      the differential diagnosis of treatment-resistant unilateral conjunctivitis. For
      definitive diagnosis, microbiological and histopathological examinations should
      be performed both in conjunctiva and regional lymph node.

PMID- 29576898
TI  - Orbital Apex Syndrome Secondary to Herpes Zoster Ophthalmicus.
AB  - Orbital apex syndrome is a rare complication of herpes zoster ophthalmicus. A
      patient being followed in our clinic for herpes zoster ophthalmicus developed
      orbital apex syndrome in the second week of treatment. Clinical diagnosis was
      supported by magnetic resonance imaging. Treatment with systemic steroid and
      antiviral therapy resulted in total regression of ophthalmoplegia at 2 months.
      However, optic neuropathy-induced vision loss was permanent. This case report
      examines orbital apex syndrome secondary to herpes zoster ophthalmicus, which has
      rarely been documented in the ophthalmic literature.

PMID- 29576899
TI  - Goldmann-Favre Syndrome: Case Series.
AB  - Goldmann-Favre syndrome, which is caused by mutation of the NR2E3 gene, is a
      retinal degenerative disease with a wide spectrum of phenotypic properties.
      Variations in clinical presentation result in difficulties in differential
      diagnosis. In this article, Goldmann-Favre syndrome cases with different clinical
      findings are presented. Clinical characteristics of our cases were reviewed and
      discussed in light of the literature.

PMID- 29576900
TI  - Three Cases of Congenital Retinal Macrovessel, One Coexisting with Cilioretinal
      Artery.
AB  - In this report, we describe three cases of retinal macrovessel. Two of the three
      patients presented to our clinic for annual eye exam and had no visual
      complaints. The third patient presented because of vision loss in the left eye.
      Two patients had 20/20 best corrected visual acuity in both eyes and the third
      patient had 20/20 in the right eye, 20/25 in the left eye. Pupillary exams were
      normal. Slit-lamp examinations of the anterior segment were unremarkable. Fundus
      examination revealed macrovessels in the left eyes of two patients and in the
      right eye of one patient. The patients underwent complete ophthalmological
      examinations including color fundus photography for all three patients and optic
      coherence tomography, fundus autoflorescence, and fundus fluorescein angiography
      for two of the patients. Cilioretinal artery coexisting with macrovessel was seen
      angiography in one case. Congenital retinal macrovessel is a rare vascular
      condition. It is often unilateral and the vessel is an aberrantly large branch of
      the retinal arteries or veins. They may cross the fovea and their visual impact
      is minimal. The coexistence of congenital retinal macrovessel and cilioretinal
      artery is very rare. Visual impairment may occur in congenital retinal
      macrovessel due to retinal cavernous hemangioma, foveal cysts, central serous
      retinopathy, and other retinal vascular abnormalities.

PMID- 29576901
TI  - Rhabdomyolysis following minimally invasive transforaminal lumbar interbody
      fusion: Case report.
AB  - Background: Rhabdomyolysis results from the release of large quantities of muscle
      cell contents into plasma resulting in a classic triad of symptoms - muscle pain,
      weakness, and brown urine. Only a handful of rhabdomyolysis cases occurring after
      spinal surgery have been reported. Case Description: A 36-year-old male underwent
      an uneventful right-sided, minimally invasive transforaminal lumbar interbody
      fusion (miTLIF) for intractable lower back pain and right lower extremity
      radiculopathy attributed to L4-S1 degenerative spondylosis (DS). Postoperatively,
      the patient complained of intractable lower extremity pain resistant to medical
      management. He was subsequently diagnosed with rhabdomyolysis, and aggressive
      intravenous fluid resuscitation resulted in complete recovery. Conclusions:
      Rhabdomyolysis should be diagnosed and treated promptly with aggressive
      intravenous fluid resuscitation to avoid acute kidney injury following miTLIF
      surgery.

PMID- 29576902
TI  - Maladjustment of programmable ventricular shunt valves by inadvertent exposure to
      a common hospital device.
AB  - Background: Programmable ventricular shunt valves are commonly used to treat
      hydrocephalus. They can be adjusted to allow for varying amounts of cerebrospinal
      fluid (CSF) flow using an external magnetic programming device, and are
      susceptible to maladjustment from inadvertent exposure to magnetic fields. Case
      Description: We describe the case of a 3-month-old girl treated for hydrocephalus
      with a programmable StrataTM II valve found at the incorrect setting on multiple
      occasions during her hospitalization despite frequent reprogramming and
      surveillance. We found that the Vocera badge, a common hands-free wireless
      communication system worn by our nursing staff, had a strong enough magnetic
      field to unintentionally change the shunt setting. The device is worn on the
      chest bringing it into close proximity to the shunt valve when care providers
      hold the baby, resulting in the maladjustment. Conclusion: Some commonly used
      medical devices have a magnetic field strong enough to alter programmable shunt
      valve settings. Here, we report that the magnetic field from the Vocera hands
      free wireless communication system, combined with the worn position, results in
      shunt maladjustment for the StrataTM II valve. Healthcare facilities using the
      Vocera badges need to put protocols in place and properly educate staff members
      to ensure the safety of patients with StrataTM II valves.

PMID- 29576903
TI  - Ruptured posterior cerebral artery aneurysm presenting with a contralateral
      cranial nerve III palsy: A case report.
AB  - Background: Posterior cerebral artery aneurysms can frequently present with an
      ipsilateral cranial nerve III palsy. Case Description: We report the first case
      of a posterior cerebral artery aneurysm associated with a contralateral cranial
      nerve III palsy. A 64-year-old male presented with acute subarachnoid hemorrhage,
      Hunt and Hess grade 3, and a left-sided fixed and dilated pupil. Computed
      tomography scan showed hemorrhage, mainly within the left basal cisterns. Digital
      subtraction angiography revealed a right-sided P1-P2 junction aneurysm.
      Conclusions: This case demonstrates that, although the neurological exam can help
      pinpoint the location of a lesion, false localizing signs should be recognized.

PMID- 29576904
TI  - Noninvasive measures of brain edema predict outcome in pediatric cerebral
      malaria.
AB  - Background: Increased brain volume (BV) and subsequent herniation are strongly
      associated with death in pediatric cerebral malaria (PCM), a leading killer of
      children in developing countries. Accurate noninvasive measures of BV are needed
      for optimal clinical trial design. Our objectives were to examine the performance
      of six different magnetic resonance imaging (MRI) BV quantification measures for
      predicting mortality in PCM and to review the advantages and disadvantages of
      each method. Methods: Receiver operator characteristics were generated from BV
      measures of MRIs of children admitted to an ongoing research project with PCM
      between 2009 and 2014. Fatal cases were matched to the next available survivor. A
      total of 78 MRIs of children aged 5 months to 13 years (mean 4.0 years), of which
      45% were males, were included. Results: Areas under the curve (AUC) with 95%
      confidence interval on measures from the initial MRIs were: Radiologist-derived
      score = 0.69 (0.58-0.79; P = 0.0037); prepontine cistern anteroposterior (AP)
      dimension = 0.70 (0.56-0.78; P = 0.0133); SamKam ratio [Rt. parietal lobe
      height/(prepontine AP dimension + fourth ventricle AP dimension)] = 0.74 (0.63
      0.83; P = 0.0002); and global cerebrospinal fluid (CSF) space ascertained by
      ClearCanvas = 0.67 (0.55-0.77; P = 0.0137). For patients with serial MRIs (n =
      37), the day 2 global CSF space AUC was 0.87 (0.71-0.96; P < 0.001) and the
      recovery factor (CSF volume day 2/CSF volume day 1) was 0.91 (0.76-0.98; P <
      0.0001). Poor prognosis is associated with radiologist score of >=7; prepontine
      cistern dimension <=3 mm; cisternal CSF volume <=7.5 ml; SamKam ratio >=6.5; and
      recovery factor <=0.75. Conclusion: All noninvasive measures of BV performed well
      in predicting death and providing a proxy measure for brain volume. Initial MRI
      assessment may inform future clinical trials for subject selection, risk
      adjustment, or stratification. Measures of temporal change may be used to stage
      PCM.

PMID- 29576905
TI  - Treatment of glenohumeral arthritis pain utilizing spinal cord stimulation.
AB  - Background: Dorsal column stimulation may be utilized to treat non-neuropathic
      pain attributed to glenohumeral arthritis. Case Description: An 84-year-old
      female presented with right shoulder pain for 3 years. She was diagnosed with
      glenohumeral arthritis and a complete loss of the joint space. She was treated
      with a dorsal column stimulator, requiring the electrodes to be placed from the
      inferior aspect of C3 to the superior aspect of T1. Six weeks postoperatively,
      she reported >90% coverage of her shoulder pain, demonstrated increased right arm
      function, and a reduction in her use of narcotics. Conclusion: Dorsal column
      stimulation of C3-T1 proved to be an effective alternative treatment for drug
      resistant glenohumeral arthritis in an 84-year-old female with a complete loss of
      the joint space.

PMID- 29576907
TI  - Spinal case of the month with short perspective: How would you treat this L3-L4
      synovial cyst?
AB  - Background: In this new section, Case of the Month with Short Perspective from
      Surgical Neurology International, we want to see how various spine surgeons would
      approach different spinal pathologies. In this first case, an elderly male
      presented with 3 years of lower back pain and progressive neurogenic claudication
      with bilateral radiculopathy that had exacerbated over the prior 6 months. An
      outside physician performed a magnetic resonance (MR) study of the lumbar spine
      that showed a massive synovial cyst filling the spinal canal (e.g., large
      bilateral cysts) at the L3-L4 level with grade I spondylolisthesis. The MR and CT
      studies also both demonstrated moderate L2-L3, and severe L3-L4 stenosis.
      Methods: Despite the massive synovial cyst filling the spinal canal at the L3-L4
      level, pain management (anesthesia training) spent 3 months performing three
      successive epidural steroid injections accompanied by attempts at percutaneous
      synovial cyst aspiration/rupture. Results: By the time the patient presented to
      neurosurgery, he had developed severe neurogenic claudication, radiculopathy,
      myelopathy, and a cauda equina syndrome. Dynamic X-rays revealed a mild grade I
      degenerative spondylolisthesis at the L3-L4 level without active motion, while
      both computed tomography (CT) and MR studies confirmed moderate stenosis
      stenosis/ossification of the yellow ligament at the L2-L3 level, severe stenosis
      at L3-L4 level with spondylolisthesis, and massive bilateral synovial cysts at
      the L3-L4 level filling the spinal canal. Conclusions: Following an L2-L4
      decompressive laminectomy without fusion (note the absence of motion
      intraoperatively at the L3-L4 level), the patient's symptoms resolved, and he
      regained normal function. How would you have managed this patient?

PMID- 29576906
TI  - Lower complication and reoperation rates for laminectomy rather than MI
      TLIF/other fusions for degenerative lumbar disease/spondylolisthesis: A review.
AB  - Background: Utilizing the spine literature, we compared the complication and
      reoperation rates for laminectomy alone vs. instrumented fusions including
      minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) for the
      surgical management of multilevel degenerative lumbar disease with/without
      degenerative spondylolisthesis (DS). Methods: Epstein compared complication and
      reoperation rates over 2 years for 137 patients undergoing laminectomy alone
      undergoing 2-3 level (58 patients) and 4-6 level (79 patients) Procedures for
      lumbar stenosis with/without DS. Results showed no new postoperative neurological
      deficits, no infections, no surgery for adjacent segment disease (ASD), 4
      patients (2.9%) who developed intraoperative cerebrospinal fluid (CSF) fistulas,
      no readmissions, and just 1 reopereation for a (postoperative day 7). These rates
      were compared to other literature for lumbar laminectomies vs. fusions (e.g.
      particularly MI TLIF) addressing pathology comparable to that listed above.
      Results: Some studies in the literature revealed an average 4.8% complication
      rate for laminectomy alone vs. 8.3% for decompressions/fusion; at 5 postoperative
      years, reoperation rates were 10.6% vs. 18.4%, respectively. Specifically, the MI
      TLIF literature complication rates ranged from 7.7% to 23.0% and included up to
      an 8.3% incidence of wound infections, 6.1% durotomies, 9.7% permanent
      neurological deficits, and 20.2% incidence of new sensory deficits. Reoperation
      rates (1.6-6%) for MI TLIF addressed instrumentation failure (2.3%), cage
      migration (1.26-2.4%), cage extrusions (0.8%), and misplaced screws (1.6%). The
      learning curve (e.g. number of cases required by a surgeon to become proficient)
      for MI TLIF was the first 33-44 cases. Furthermore, hospital costs for lumbar
      fusions were 2.6 fold greater than those for laminectomy alone, with overall
      neurosurgeon reimbursement quoted in one study as high as $142,075 per year.
      Conclusions: The spinal literature revealed lower complication and reoperation
      rates for lumbar laminectomy alone vs. higher rates for instrumented fusion,
      including MI TLIF, for degenerative lumbar disease with/without DS.

PMID- 29576908
TI  - Rare case of a rapidly enlarging symptomatic arachnoid cyst of the posterior
      fossa in an infant: A case report and review of the literature.
AB  - Background: Intracranial arachnoid cysts are space-occupying lesions that
      typically remain stable or decrease in size over time. Cysts in infants younger
      than 1 year of age are remarkably different from those in older children and
      adults in terms of cyst localization and enlargement. Arachnoid cysts of the
      posterior fossa (PFACs) are very rare in infants and do not typically grow or
      present with clinical symptoms, such that surgical treatment is generally
      considered to be unnecessary. Here, we describe an extremely rare case of an
      infant with a rapidly enlarging symptomatic PFAC that was successfully treated
      with surgery. Case Description: A 4-month-old boy presented with increasing head
      circumference and a rapidly enlarging arachnoid cyst in the left posterior fossa
      with ventriculomegaly, which was documented using serial imaging over the
      preceding 2 months. We performed a microscopic resection of the cyst membrane to
      remove the mass effect as soon as possible and facilitate normal development. To
      confirm dural closure and prevent cerebrospinal fluid leakage, we also performed
      short-term (7 days) percutaneous long-tunneled external ventricle drainage after
      the surgery. Magnetic resonance imaging over a 4-year follow-up period revealed
      adequate reduction of the ventricle and cyst. The patient no longer exhibited
      progressive macrocrania and showed normal development. Conclusion: To our
      knowledge, this is the second successful case of surgical treatment of an
      enlarging symptomatic PFAC in an infant. Our surgical strategy for the treatment
      of this rare case can serve as a guide for surgeons in similar future cases.

PMID- 29576909
TI  - Deep brain stimulation for Alzheimer's Disease: An update.
AB  - Background: Dementia is among the leading causes of severe and long-term
      disability worldwide, decreasing the quality of life of individuals and families.
      Moreover, it induces an enormous economic burden on societies. The most prevalent
      cause of dementia is Alzheimer's disease (AD). Because current treatment options
      for AD are limited, deep brain stimulation (DBS) has been considered. Methods:
      The aim of this review is to survey the current understanding regarding the
      effects of DBS in AD and possibly shed light on the mechanisms of DBS in AD. We
      searched PubMed and Cochrane for various studies in English literature describing
      DBS in patients with AD and relevant preclinical studies. All related studies
      published from December 2013 to March 2017 were included in this review. Results:
      Our understanding of the neural circuitry underlying learning and memory in both
      rodent models and human patients has grown over the past years and provided
      potential therapeutic targets for DBS such as the fornix and the nucleus basalis
      of Meynert. Clinical results indicate that DBS is most beneficial for patients
      who are in the early stages of AD. Potential mechanisms of action of DBS in AD
      comprise long-term structural plasticity, including hippocampal enlargement as
      well as enhanced neurotransmitter release. Conclusion: It is still premature to
      conclude that DBS can be used in the treatment of AD, and the field will wait for
      the results of ongoing and future clinical trials.

PMID- 29576910
TI  - Does Race Matter in Addressing Homelessness? A Review of the Literature.
AB  - Since the 1980s, black persons have been overrepresented in the United States
      homeless population. Given that morbidity and mortality is elevated among both
      the black population and the homeless population in comparison to the general
      U.S. population, this overrepresentation has important implications for health
      policy. However, the racial demographics of homelessness have received little
      attention from policymakers. This article reviews published social and behavioral
      science literature that addresses the relationship between race and contemporary
      homelessness in the United States. This literature points to substantial
      differences between racial subgroups of the U.S. homeless population in
      vulnerabilities, health risks, behaviors, and service outcomes. Such observed
      differences suggest that policies and programs to prevent and end homelessness
      must explicitly consider race as a factor in order to be of maximum
      effectiveness. The limited scope of these findings also suggests that more
      research is needed to better understand these differences and their implications.

PMID- 29576912
TI  - Current Concept in the Treatment of Scaphoid Nonunion.

PMID- 29576911
TI  - Stereoselective olefin cyclopropanation under aerobic conditions with an
      artificial enzyme incorporating an iron-chlorin e6 cofactor.
AB  - Myoglobin has recently emerged as a promising biocatalyst for catalyzing carbene
      mediated cyclopropanation, a synthetically valuable transformation not found in
      nature. Having naturally evolved for binding dioxygen, the carbene transferase
      activity of this metalloprotein is severely inhibited by it, imposing the need
      for strictly anaerobic conditions to conduct these reactions. In this report, we
      describe how substitution of the native heme cofactor with an iron-chlorin e6
      complex enabled the development of a biocatalyst capable of promoting the
      cyclopropanation of vinylarenes with high catalytic efficiency (up to 6,970 TON),
      turnover rate (>2,000 turnovers/min), and stereoselectivity (up to 99% de and ee)
      in the presence of oxygen. The artificial metalloenzyme can be recombinantly
      expressed in bacterial cells, enabling its application also in the context of
      whole-cell biotransformations. This work makes available a robust and easy-to-use
      oxygen-tolerant biocatalyst for asymmetric cyclopropanations and demonstrates the
      value of porphyrin ligand substitution as a strategy for tuning and enhancing the
      catalytic properties of hemoproteins in the context of abiological reactions.

PMID- 29576913
TI  - Current Management of Scaphoid Nonunion Based on the Biomechanical Study.
AB  - Scaphoid nonunion causes abnormal wrist kinematics and typically leads to carpal
      collapse and subsequent degenerative arthritis of the wrist. However, the natural
      history, including carpal collapse and degenerative arthritis of scaphoid
      nonunion, may vary at different fracture locations. This article reviews recent
      biomechanical studies related to the natural history of scaphoid nonunion. In the
      distal-type fractures (type B2 in Herbert classification), where the fracture
      located distal to the scaphoid apex, the proximal scaphoid fragment and lunate,
      which are connected through the dorsal scapholunate interosseous ligament (DSLIL)
      and dorsal intercarpal ligament (DIC), extend together, and the distal fragment
      of the scaphoid flexes individually. Therefore, untreated type B2 fractures
      normally show the humpback deformity, resulting in dorsal intercalated segment
      instability deformity relatively earlier after the injury. In the proximal-type
      fractures (type B1), where the fracture is located proximal to the scaphoid apex,
      the connection between the distal fragment and lunate is preserved through the
      DSLIL and DIC so that the scaphoid-lunate complex remains stable and the carpal
      collapse is less severe than that in distal-type fractures. The fracture location
      relative to the apex of the dorsal scaphoid ridge is a reliable landmark in the
      determination of the natural history of scaphoid nonunion.

PMID- 29576914
TI  - Biomechanics of an Articulated Screw in Acute Scapholunate Ligament Disruption.
AB  - Background  An injury to the scapholunate interosseous ligament (SLIL) leads to
      instability in the scapholunate joint. Temporary fixation is used to protect the
      ligament during reconstruction or healing of the repair. Rigid screw fixation-by
      blocking relative physiological motion between the scaphoid and lunate-can lead
      to screw loosening, pullout, and fracture. Purpose  This study aims to evaluate
      changes in scaphoid and lunate kinematics following SLIL injury and the
      effectiveness of an articulating screw at restoring preinjury motion. Materials
      and Methods  The kinematics of the scaphoid and lunate were measured in 10
      cadaver wrists through three motions driven by a motion simulator. The specimens
      were tested intact, immediately following SLIL injury, after subsequent cycling,
      and after fixation with a screw. Results  Significant changes in scaphoid and
      lunate motion occurred following SLIL injury. Postinjury cycling increased motion
      changes in flexion-extension and radial-ulnar deviation. The motion was not
      significantly different from the intact scapholunate joint after placement of the
      articulating screw. Conclusion  In agreement with other studies, sectioning of
      the SLIL led to significant kinematic changes of the scaphoid and lunate in all
      motions tested. Compared with intact scapholunate joint, no significant
      difference in kinematics was found after placement of the screw indicating a
      correction of some of the changes produced by SLIL transection. These findings
      suggest that the articulating screw may be effective for protecting a SLIL repair
      while allowing the physiological rotation to occur between the scaphoid and
      lunate. Clinical Relevance  A less rigid construct, such as the articulating
      screw, may allow earlier wrist rehabilitation with less screw pullout or failure.

PMID- 29576915
TI  - A New Wrist Clinical Evaluation Score.
AB  - Background  The number of available wrist scoring systems is limited; some of
      them do not include forearm rotation criteria. Purpose  To describe a new
      electronic wrist clinical score and to present a new patient's generated wrist
      evaluation criterion, the subjective wrist value (SWV). Materials and Methods  A
      new electronic wrist clinical score, the Lyon wrist score (LWS) including wrist
      VAS pain and function, active range of motion and strength was built into an
      excel file. VAS flexion-extension pain and function were evaluated independently
      from pronation-supination pain and function. A new patient's generated wrist
      evaluation criterion, SWV was described. Results  The LWS is available in two
      versions, standard and full (the latter including forearm rotation strength).
      Both standard and full LWS are displayed into an automatically generated diamond
      shaped graph providing a comprehensive visual display of the clinical status of
      most osteoarticular wrist disorders. The graph also includes SWV. The LWS,
      combined with SWV into a graph that may be directly exported to a PowerPoint
      presentation, provide a new practical and comprehensive tool for
      following/comparing wrist osteoarticular clinical status/outcomes. Both standard
      and full LWS charts are available in colored versions on a related website for
      free download. Conclusion  A comprehensive updated electronic display of
      osteoarticular wrist clinical status including forearm rotation criteria is
      provided and displayed into a graph which may be exported as such into a
      PowerPoint presentation for clinical analysis/comparisons. Level of Evidence 
      Level II.

PMID- 29576916
TI  - Deferring Routine Wrist Radiography Does Not Affect Management of de Quervain
      Tendinopathy Patients.
AB  - Background  Obtaining wrist radiographs prior to surgeon evaluation may be
      wasteful for patients ultimately diagnosed with de Quervain tendinopathy (DQT).
      Questions/Purpose  Our primary question was whether radiographs directly
      influence treatment of patients presenting with DQT. A secondary question was
      whether radiographs influence the frequency of injection and surgical release
      between cohorts with and without radiographs evaluated within the same practice.
      Patients and Methods  Patients diagnosed with DQT by fellowship-trained hand
      surgeons at an urban academic medical center were identified retrospectively.
      Basic demographics and radiographic findings were tabulated. Clinical records
      were studied to determine whether radiographic findings corroborated history or
      physical examination findings, and whether management was directly influenced by
      radiographic findings. Frequencies of treatment with injection and surgery were
      separately tabulated and compared between cohorts with and without radiographs.
      Results  We included 181 patients (189 wrists), with no differences in
      demographics between the 58% (110 wrists) with and 42% (79 wrists) without
      radiographs. Fifty (45%) of imaged wrists demonstrated one or more abnormalities;
      however, even for the 13 (12%) with corroborating history and physical
      examination findings, wrist radiography did not directly influence a change in
      management for any patient in this series. No difference was observed in rates of
      injection or surgical release either upon initial presentation, or at most recent
      documented follow-up, between those with and without radiographs. No differences
      in frequency, types, or total number of additional simultaneous surgical
      procedures were observed for those treated surgically. Conclusion  Wrist
      radiography does not influence management of patients presenting DQT. Level of
      Evidence  This is a level III, diagnostic study.

PMID- 29576917
TI  - Results of the Universal 2 Prosthesis in Noninflammatory Osteoarthritic Wrists.
AB  - Background/Purpose  Many treatment options are available for wrist
      osteoarthritis, with the objective of decreasing pain and preserving function. In
      later stages when midcarpal and radiocarpal osteoarthritis occur, two choices
      remain: total wrist arthrodesis or total wrist arthroplasty. The purpose of this
      study is to present the short-term functional changes following total wrist
      arthroplasty with the Universal 2 total wrist system (Integra Life Sciences) in
      patients with noninflammatory wrist osteoarthritis. Patients and Methods 
      Patients with severe noninflammatory wrist osteoarthritis were assessed
      preoperatively, 6 and 12 months after surgery using a range of motion, grip
      strength, pain, and the disabilities of the arm, shoulder, and hand (DASH) score.
      The additional assessment was performed after 1 year for a range of motion using
      a biaxial electrogoniometer, grip strength, DASH, and the Michigan hand
      questionnaire. Results  All range of motion directions and grip strength did not
      change from preoperative values. The DASH score improved from 53 preoperatively
      to 14 during latest follow-up. Median patients' satisfaction score decreased with
      approximately 20 points during the last follow-up. Conclusion  The relatively
      good DASH score combined with the partly maintained wrist range of motion
      indicates that reconstruction with the Universal 2 total wrist prosthesis should
      be considered in patients with end-stage noninflammatory wrist osteoarthritis.
      Level of Evidence  Level IV, therapeutic study.

PMID- 29576918
TI  - Nonspanning Total Wrist Arthrodesis with a Low-Profile Locking Plate.
AB  - Purpose  This study aims to compare the outcomes and complications of our
      technique for nonspanning total wrist arthrodesis using a locking plate with the
      standard carpometacarpal spanning technique. Methods  A retrospective review of
      charts was performed to identify patients who underwent total wrist arthrodesis
      by the senior author (S.W.W.). We compared the outcomes of 15 cases of
      nonspanning wrist fusion with a 2.4/2.7 mm locking T plate to 11 cases of
      spanning wrist fusion with a 2.7/3.5 mm locking compression plate. Minimum follow
      up was 3 months. Indications for fusion included rheumatoid arthritis,
      posttraumatic arthritis, Kienbock's disease, primary osteoarthritis, juvenile
      inflammatory arthropathy, psoriasis, brachial plexopathy, failed hemi or total
      wrist arthroplasty, failed four-corner fusion, and failed proximal row
      carpectomy. The primary outcome was fusion. Secondary outcomes included time to
      union, patient-rated wrist evaluation score, numerical rating scale pain score,
      grip strength, and complications. Results  All the wrists got fused. There were
      no significant differences in objective and subjective outcomes between cohorts.
      There were three complications (27%) in the spanning group, including tendon
      rupture and peri-implant fracture at the third metacarpal. This was compared with
      three complications (20%) in the nonspanning group, consisting of hardware
      removal. Discussion  We achieved similar fusion rates employing both spanning and
      nonspanning total wrist arthrodesis techniques, without necessitating
      carpometacarpal arthrodesis in the latter. Complications associated with our
      method were comparably less severe than those reported in the literature. We
      advocate nonspanning arthrodesis as an alternative method for total wrist fusion
      with a high union rate and minimal risk of complications at the carpometacarpal
      joint. Level of Evidence  Therapeutic level IV.

PMID- 29576919
TI  - Treatment of Ulnar Impaction Syndrome with and without Central TFC Lesion.
AB  - Background  Arthroscopic debridement of the triangular fibrocartilage (TFC) is
      well accepted in patients with ulnar impaction syndrome with central TFC lesions.
      Treatment remains controversial, however, when there is no such lesion from
      radiocarpal view. Purpose  This study assessed the clinical outcome of
      arthroscopic central TFC resection and debridement and secondary ulnar shortening
      in patients with ulnar impaction with central TFC lesion compared with patients
      without TFC lesion. Patients and Methods  Thirty-two consecutive patients with
      ulnar impaction syndrome were arthroscopically treated, 16 of whom had a central
      lesion of the TFC that was debrided. In the 16 patients with no lesion from the
      radiocarpal view, the TFC was centrally resected and debrided to decompress the
      ulnocarpal joint. Persisting symptoms necessitated ulnar shortening in four
      patients in each group. Two patients underwent repeat arthroscopic TFC
      debridement. All patients were examined at 3, 6, and 12 months, and at final
      follow-up (mean: 1.7 years) following arthroscopy, respectively ulnar shortening
      or hardware removal. Results  In both groups, pain, Krimmer, and DASH scores
      significantly improved. Improvements of DASH scores were significantly higher in
      patients without lesion at 12 months and at final follow-up. For other
      parameters, no significant difference was found between the two groups.
      Conclusion  In both situations, with and without central TFC lesion, resection
      and debridement sufficiently reduced the ulnar-sided wrist pain and improved
      function in three out of four patients, and therefore qualified as the first-line
      treatment of ulnar impaction syndrome as arthroscopy is performed, anyway. Those
      patients who complained of persisting or recurrent ulnar-sided wrist pain finally
      benefitted from ulnar shortening osteotomy as the secondary procedure. Level of
      Evidence  Therapeutic III, case-control study.

PMID- 29576920
TI  - Cadaveric Testing of a Novel Scapholunate Ligament Reconstruction.
AB  - Background  Existing scapholunate interosseous ligament (SLIL) reconstruction
      techniques include fixation spanning the radiocarpal joint, which do not reduce
      the volar aspect of the scapholunate interval and may limit wrist motion.
      Questions/Purpose  This study tested the ability of an SLIL reconstruction
      technique that approximates both the volar and dorsal scapholunate intervals,
      without spanning the radiocarpal joint, to restore static scapholunate
      relationships. Materials and Methods  Scapholunate interval, scapholunate angle,
      and radiolunate angle were measured in nine human cadaveric specimens with the
      SLIL intact, sectioned, and reconstructed. Fluoroscopic images were obtained in
      six wrist positions. The reconstruction was performed by passing tendon graft
      through bone tunnels from the dorsal surface toward the volar corner of the
      interosseous surface. After reduction of the scapholunate articulation, the graft
      was tensioned within the lunate bone tunnel, secured with an interference screw
      in the scaphoid, and sutured to the dorsal SLIL remnant. Differences among
      testing states were evaluated using repeated measures ANOVA. Results  There was a
      significant increase in the scapholunate interval in all wrist positions after
      complete SLIL disruption. Compared with the disrupted state, there was a
      significant decrease in scapholunate interval in all wrist positions after
      reconstruction using a tendon graft and interference screw. Conclusion  Our SLIL
      reconstruction technique reconstructs the volar and dorsal ligaments of the
      scapholunate joint and adequately restores static measures of scapholunate
      stability. This technique does not tether the radiocarpal joint and aims to
      optimize volar reduction. Clinical Relevance  Our technique offers an alternative
      option for SLIL reconstruction that successfully restores static scapholunate
      relationships.

PMID- 29576921
TI  - Morphological Associations between the Distal Radioulnar Joint and the Lunate.
AB  - Background  Variations in morphology of the carpal bones have been described.
      Their implication in wrist disease and specific kinematic features has been
      recognized, and a better knowledge of these variations is essential.
      Questions/Purpose  To radiographically determine any association between the
      morphological variations of the distal radioulnar joint (DRUJ) and the lunate
      bone. Materials and Methods  Radiographs of 100 wrists of patients presenting to
      the emergency department with wrist pain and referred to our outpatient clinic
      were retrospectively reviewed for DRUJ inclination, ulnar variance, and
      radiocarpal and midcarpal morphology of the lunate. Results  There were 51
      females and 49 males, mean age 51.2 years (range: 21-94). There was a
      statistically significant association between the DRUJ inclination and the
      morphology of the radiocarpal side of the lunate ( p  < 0.001). The mean values
      of ulnar variance changed according to DRUJ inclination and the radiocarpal side
      of the lunate ( p  < 0.001) but not according to the midcarpal side of the
      lunate. There was no significant association between the morphology of the DRUJ
      and the midcarpal side of the lunate or between the midcarpal and the radiocarpal
      morphology of the lunate. Conclusion  This study demonstrated a statistically
      significant association at the radiocarpal level between the DRUJ inclination,
      ulnar variance, and the morphology of the lunate. No association was found with
      the morphology of the midcarpal side of the lunate. Accordingly, a classification
      of these carpal associations is proposed, highlighting seven main wrist
      configurations. Clinical Relevance  These associations can guide future studies
      of wrist kinematics.

PMID- 29576922
TI  - Botox and Thumb MCP Radial Collateral Ligament Reconstruction.
AB  - Background  We report the use of botulinum toxin to aid in the treatment of
      chronic radial collateral ligament insufficiency of the thumb. Case Description 
      Treatment included autograft tendon reconstruction and cast immobilization. Six
      weeks postoperatively, prior to hand therapy, the patient underwent an ultrasound
      guided botulinum neurotoxin A injection into the adductor pollicis muscle to
      negate its deforming forces on the reconstruction. The patient made an excellent
      recovery and 1 year postoperatively was pain free and had a stable radial
      collateral ligament (RCL) upon examination. Literature Review  The outcomes of
      RCL repair and reconstruction are unpredictable, in part, due to the strong
      opposing forces of the adductor pollicis. Clinical Relevance  The use of Botox
      injection may enhance the outcomes of RCL repair or reconstruction by
      neutralizing the deforming forces of the adductor muscle.

PMID- 29576923
TI  - Ulnar Lengthening/Reconstruction of Interosseous Membrane in Treatment of
      Osteochondroma.
AB  - Background:  We aim to measure the quality of life and clinical and functional
      outcomes of a patient who had undergone ligament reconstruction of the forearm
      interosseous membrane, using brachioradialis tendon more ulna distraction
      osteogenesis in treatment with multiple cartilaginous exostosis. Case
      Description:  We present a 11-year-old boy with congenital deformity in his
      right, dominant forearm,Type IIb by Masada classification. Distraction of the
      ulna, resection of exostosis, and reconstruction of the distal part of the
      interosseous membrane was performed. One year later, the patient experienced good
      evaluation. Wrist flexion was 70 degrees, extension was 60 degrees, radial
      deviation was 20 degrees, and ulnar deviation was 30 degrees. Forearm pronation
      was 60 degrees and supination was 90 degrees. Elbow flexion was 120 degrees,
      extension was -5 degrees, and digit motion was full. DASH score of 5, VAS of 0,
      and grip strength of 92% compared to the unaffected side were obtained. Forearm
      radiographic aspects showed healing of the distraction, articular congruency, the
      distal radioulnar joint (DRUJ), and radiocapitellum joint. The distraction
      distance was 28 mm, the distraction period was 67 days, the consolidation period
      was 96 days, and the period of fixator treatment was 92 days. The distraction
      speed was 0.5 mm/day. Good stability and joint congruency of the DRUJ and elbow
      were obtained. Good radiographic, clinical, and functional results were obtained
      improving the life quality of that patient. Literature Review:  The treatment of
      forearm deformities is difficult and complicated. There is no consensus to the
      overall management. As there is still a lack of long-term results, the
      indications for surgery, various surgical options, and the timing of the
      intervention have been a matter of controversy in the literature. Would DRUJ be
      stable when ulnar lengthening is combined with excision of exostosis? Is it
      possible to reduce the radial head with this technique? Clinical Relevance:  We
      would like to suggest an interosseous membrane (distal oblique band)
      reconstruction to improve this treatment. We believe this suggestion could
      maintain DRUJ and elbow more stable and functional. We agree that the best time
      to perform the corrections is early and gradually. We prefer to correct the ulna,
      radius, DRUJ and elbow in many steps than in only one procedure.

PMID- 29576924
TI  - Arthroscopic Synovectomy Combined with Autologous Fat Grafting in Early Stages of
      CMC Osteoarthritis of the Thumb.
AB  - Background  Minimal invasive treatments such as arthroscopic techniques may be
      adequate to restore the anatomy and functional integrity of the thumb CMC
      (carpometacarpal) joint. In this paper, we reported the interposition of
      autologous fat tissue in combination with arthroscopic synovectomy/debridement
      for early stage of the thumb CMC joint osteoarthritis. Patients and Methods 
      Twelve patients with a mean age of 46 years with early radiological stages of
      thumb CMC joint osteoarthritis were included. Evaluation of outcome was measured
      prior and 3, 12, and 24 months after surgery including, Visual Analog Scale
      (VAS), QuickDASH, grip and pinch strength, range of motion (ROM), and patient
      satisfaction. Results  Pain at rest (or with load) was reduced from preoperative
      4,7 (8,7) to 2 (5,9) at 3 to 6 months; 1,4 (4,3) at 12 months; and 0,75 (2,7) at
      2 years after the surgery. Initial preoperative QuickDASH value of 52 points
      reduced to 33 (17-65) at 6 months, 23 (2-70) at 12 months, and 20 (11-29) at 24
      months after the surgery. Grip strength and thumb pinch with respect to the
      contralateral untreated thumb was reduced in the first 12 months but recovered
      subsequently. ROM was equal to the contralateral thumb. Three patients suffered
      from tendinitis and required surgical treatment. One patient indicated prolonged
      pain symptoms. No infections were noted and no donor-site morbidity or side
      effects were detected. Conclusion  Arthroscopic synovectomy combined with
      autologous fat graft is a reliable surgical option for early thumb CMC joint
      osteoarthritis and that effect continues for more than 24 months.

PMID- 29576925
TI  - Effects of Ulnar Styloid Fractures on Unstable Distal Radius Fracture Outcomes: A
      Systematic Review of Comparative Studies.
AB  - Purpose  In this literature review, functional outcomes such as Disability of
      Arm, Shoulder and Hand (DASH) score and the visual analog scale (VAS) of pain
      along with clinical outcomes such as range of movement and grip strength of
      treated distal radius fractures (DRF) accompanied with ulnar styloid fractures
      (USF) will be compared with those with isolated DRF. Materials and Methods  We
      analyzed articles from MEDLINE, Embase, and CINAHL that met our predetermined
      inclusion and exclusion criteria as per the Preferred Reporting Items for
      Systematic Reviews and Meta-analysis statements. This resulted in the
      identification of 464 articles with 18 potentially eligible studies of which 6
      were included at the full-text screening stage. The primary outcomes were wrist
      pain, range of motion, functional outcome and satisfaction, such as VAS, and the
      DASH questionnaire along with radiological assessment and incidence of
      complications. Results  These studies involved 796 participants with DRF and 806
      wrists with DRF; 444 (55%) of DRF had an associated USF. Three studies did not
      report any statistically significant difference in DASH scores between the DRF
      patients with or without USF. Two studies reported worse DASH scores in the group
      with associated USF. Wrist pain was reported to be statistically significantly
      worse in patients with associated USF in two studies. Grip strength did not
      exhibit a statistically significant difference in any groups in four studies. On
      assessing the range of motion of the wrist and forearm, only one study reported a
      statistically significant difference in flexion at 2 years follow-up, with less
      flexion in patients with USF. Conclusion  This review suggests that there is no
      significant correlation between a USF and the functional and clinical outcomes of
      DRF treatment, albeit wrist pain and less flexion were reported in some studies
      to be associated with USF. There is a need for more robust evidence from large
      randomized controlled trials to specifically look at the effects of fixation
      versus nonfixation of USF on DRF, or large prospective cohort studies assessing
      DRF with and without USF, with a minimum of 12 months follow-up. Level of
      Evidence  Level II-therapeutic.

PMID- 29576926
TI  - An Aberrant Abductor Digiti Minimi Muscle Crossing Guyon's Canal with
      Intermittent Compression of Nerve: Crucial Diagnostic Role of Nerve and Muscle
      Ultrasound.

PMID- 29576927
TI  - Encapsulated Cell Technology-Based Delivery of a Complement Inhibitor Reduces
      Choroidal Neovascularization in a Mouse Model.
AB  - Purpose: Age-related macular degeneration (AMD) is a slowly progressing disease,
      and risk appears to be tied to an overactive complement system. We have
      previously demonstrated that mouse choroidal neovascularization (CNV) and smoke
      induced ocular pathology can be reduced with an alternative pathway (AP)
      inhibitor fusion protein consisting of a complement receptor-2 fragment linked to
      the inhibitory domain of factor H (CR2-fH) when delivered systemically. Here we
      developed an experimental approach with genetically engineered encapsulated ARPE
      19 cells to produce CR2-fH intravitreally. Methods: ARPE-19 cells were generated
      to stably express CR2 or CR2-fH, microencapsulated using sodium alginate, and
      injected intravitreally into 2-month-old C57BL/6J mice. CNV was induced using
      argon laser photocoagulation 4 weeks postinjection. Presence of capsules and
      progression of CNV was analyzed using optical coherence tomography.
      Bioavailability of CR2-fH was evaluated in retina sections by
      immunohistochemistry, and efficacy as an AP inhibitor by C3a ELISA. Results:
      Secretion of CR2-fH or CR2 from encapsulated ARPE-19 cells was confirmed. An
      efficacious concentration of CR2-fH capsules to reduce CNV was identified.
      Bioavailability studies showed that CR2-fH was present in capsules and retinas of
      injected mice, and reduced CNV-associated ocular C3a production. Conclusions:
      These findings indicate that the AP inhibitor CR2-fH, when generated
      intravitreally, can reduce CNV in mouse. Translational Relevance: Encapsulated
      ARPE-19 cells secreting CR2-fH or perhaps other antiangiogenic or prosurvival
      factors might be useful as a potential therapeutic tool to treat age-related
      macular degeneration.

PMID- 29576928
TI  - Interindividual Variations in Foveal Anatomy and Artifacts Seen on Inner Retinal
      Probability Maps from Spectral Domain OCT Scans of the Macula.
AB  - Purpose: We tested the hypothesis that variations in foveal morphology can
      account for artifacts seen on optical coherence tomography (OCT) retinal ganglion
      cell (RGC) layer probability maps. Methods: A total of 126 healthy subjects were
      tested with spectral domain (sd) OCT. Thickness and probability maps of the
      macular RGC plus inner plexiform layer (RGC+) were obtained with customized
      software. Macular b-scans were analyzed to derive three foveal anatomic
      parameters: width, depth, and slope. The distribution of these parameters was
      compared between eyes with and without circumfoveal artifacts seen in the central
      4 degrees  of macular RGC+ probability maps. Results: Of 126 healthy subjects, 12
      (9.5%) had an abnormal circumfoveal region (artifact) on RGC+ probability maps.
      Based upon the normal distribution of the three anatomic parameters, only three
      of the 12 eyes (25%) fell outside the 95% confidence interval of one or more of
      the three foveal morphologic parameters. Multivariable logistic regression
      revealed that the parameter slope was significantly associated with the presence
      of these artifacts (odds ratio = 0.26; P = 0.019). However, the combination of
      these parameters and age explained only 11% of the total variance of these
      artifacts. Conclusions: Fovea morphology, as measured based upon width, depth,
      and slope, has a minor role in explaining artifacts seen on macular scans.
      Variations in the distribution of RGC+ thickness that are not reflected in our
      measures warrant further investigation as potential sources of artifacts.
      Translational Relevance: A small proportion of circumfoveal artifacts seen on
      RGC+ probability maps can be explained by variations in foveal anatomy.

PMID- 29576929
TI  - Customizing Perimetric Locations Based on En Face Images of Retinal Nerve Fiber
      Bundles With Glaucomatous Damage.
AB  - Purpose: Prior studies suggested the use of customized perimetric locations in
      glaucoma; these studies were limited by imaging only the superficial depths of
      the retinal nerve fiber layer (RNFL) and by prolonged perimetric testing. We
      aimed to develop a rapid perimetric test guided by high-resolution images of RNFL
      bundles. Methods: We recruited 10 patients with glaucoma, ages 56 to 80 years,
      median 68 years, and 10 controls, ages 55 to 77 years, median 68 years. The
      patients were selected based on discrepancies between locations of glaucomatous
      damage for perimetric and structural measures. Montaging was used to produce
      optical coherence tomography en face images of the RNFL covering much of the 24-2
      grid locations. In experiment 1, we presented the Goldmann size III stimulus at
      preselected retinal locations of glaucomatous damage, using just two contrasts.
      In experiment 2, we developed an elongated sinusoidal stimulus, aligned within
      the defect, to measure contrast sensitivities; abnormalities were defined based
      on lower 95% reference limits derived from the controls. Results: The percentage
      of predicted locations where size III was not seen at 28 dB ranged from 16% to
      80%, with a median of 48%. Contrast sensitivity for the sinusoidal stimulus was
      below the 95% reference range for 37 of 44 stimuli aligned within the defects.
      Conclusions: We developed methods for rapid perimetric testing guided by en face
      images of the RNFL bundles in patients with glaucoma. Results indicated ganglion
      cell damage under all of the visible RNFL defects. Translational Relevance:
      Customized perimetric locations have potential to improve clinical assessment of
      glaucoma.

PMID- 29576930
TI  - Retinal Vessel Diameters Change Within 1 Hour of Intracranial Pressure Lowering.
AB  - Purpose: We tested the hypotheses that retinal venule diameter (Dv) is associated
      with baseline intracranial pressure (ICP) level and that Dv is reduced shortly
      after ICP lowering. Methods: Dv and arteriole diameter (Da) were extracted from
      scanning laser ophthalmoscopic images in 40 eyes of 20 adult human subjects (10
      with and 10 without papilledema) immediately before and after measurement of ICP
      (range, 10-55 cm H2O) and ICP lowering by cerebrospinal fluid (CSF) drainage via
      lumbar puncture (LP). Generalized estimating equations (GEE) modeled the
      relationship between baseline ICP, Da and Dv before LP. Additional GEE modeled
      the relationship between initial ICP and change in Da and Dv (post-LP - pre-LP)
      following ICP lowering. Results: Test-retest variability of diameter measurements
      ranged from 0.1 to 2.9 MUm (0.1%-2.72%). Neither Da nor Dv pre-LP was associated
      with baseline ICP level (P = 0.140 Dv, P = 0.914 Da, GEE). Da and Dv change after
      ICP lowering was associated with baseline ICP, with vessel diameters increasing
      with lower baseline ICP and decreasing with elevated initial ICP (P = 0.030
      baseline ICP vs. Dv change, P = 0.012 baseline ICP vs. Da change, GEE models).
      Conclusions: Retina arteriole and venule diameters change immediately following
      ICP lowering. The direction of change is dependent on the initial ICP; both
      increased in subjects with high ICP and both decreased in subjects with normal
      ICP. Translational Relevance: The relationship between initial ICP and direction
      of retinal vessel size change following ICP lowering suggests a potential effect
      of ICP on cerebral and ocular hemodynamics that is relevant when considering the
      use of retinal vessel measurements as a clinical marker of ICP change.

PMID- 29576931
TI  - Gaze Following is Related to the Broader Autism Phenotype in a Sex-Specific Way:
      Building the Case for Distinct Male and Female Autism Phenotypes.
AB  - The search for a female autism phenotype is difficult, given the low diagnostic
      rates in females. Here, we studied potential sex differences in a core feature of
      autism, difficulty with eye gaze processing, among typically developing
      individuals who vary in the broad autism phenotype, which includes autistic-like
      traits that are common, continuously distributed, and similarly heritable in
      males and females. Participants viewed complex images of an actor in a
      naturalistic scene looking at one of many possible objects and had to identify
      the target gazed-at object. Among males, those high in autistic-like traits
      exhibited worse eye gaze following performance than did those low in these
      traits. Among females, eye gaze following behavior did not vary with autistic
      like traits. These results suggest that deficient eye gaze following behavior is
      part of the broader autism phenotype for males, but may not be a part of the
      female autism phenotype.

PMID- 29576932
TI  - Anticipatory Postural Adjustments and kinematic arm features when postural
      stability is manipulated.
AB  - Beyond the classical paradigm that presents the Anticipatory Postural Adjustments
      (APAs) as a manner to create forces that counteract disturbances arising from the
      moving segment during a pointing task, there is a controversial discussion about
      the role APAs to facilitate the movement and perform a task accurately. In
      addition, arm kinematics features are classically used to infer the content of
      motor planning for the execution and the control of arm movements. The present
      study aimed to disentangle the conflicting role of APAs during an arm-pointing
      task in which the subjects reach a central diode that suddenly turns on, while
      their postural stability was manipulated. Three postures were applied: Standing
      (Up), Sit without feet support (SitUnsup) and Sit with feet support (SitSup). We
      found that challenging postural stability induced an increase of the reaction
      time and movement duration (observed for the SitUnsup compared to SitSUp and Up)
      as well as modified the upper-limb velocity profile. Indeed, a greater max
      velocity and a shorter deceleration time were observed under the highest
      stability (SitSup). Thus, these Kinematics features reflect less challenging task
      and simple motor plan when the body is stabilized. Concerning the APAs, we
      observed the presence of them independently of the postural stability. Such a
      result strongly suggests that APAs act to facilitate the limb movement and to
      counteract perturbation forces. In conclusion, the degree of stability seems
      particularly tuned to the motor planning of the upper-limb during a pointing task
      whereas the postural chain (sitting vs. standing) was also determinant for APAs.

PMID- 29576933
TI  - Strong genetic differentiation in tropical seagrass Enhalus acoroides
      (Hydrocharitaceae) at the Indo-Malay Archipelago revealed by microsatellite DNA.
AB  - The Indo-Malay Archipelago is regarded as a barrier that separates organisms of
      the Indian and Pacific Oceans. Previous studies of marine biota from this region
      have found a variety of biogeographic barriers, seemingly dependent on taxon and
      methodology. Several hypotheses, such as emergence of the Sunda Shelf and recent
      physical oceanography, have been proposed to account for the genetic structuring
      of marine organisms in this region. Here, we used six microsatellite loci to
      infer genetic diversity, population differentiation and phylogeographic patterns
      of Enhalus acoroides across the Indo-Malay Archipelago. Heterozygosities were
      consistently high, and significant isolation-by-distance, consistent with
      restricted gene flow, was observed. Both a neighbour joining tree based on DA
      distance and Bayesian clustering revealed three major clusters of E. acoroides.
      Our results indicate that phylogeographic patterns of E. acoroides have possibly
      been influenced by glaciation and deglaciation during the Pleistocene. Recent
      physical oceanography such as the South Java Current and the Seasonally Reversing
      Current may also play a role in shaping the genetic patterns of E. acoroides.

PMID- 29576934
TI  - Out of Asia: mitochondrial evolutionary history of the globally introduced
      supralittoral isopod Ligia exotica.
AB  - The native ranges and invasion histories of many marine species remain elusive
      due to a dynamic dispersal process via marine vessels. Molecular markers can aid
      in identification of native ranges and elucidation of the introduction and
      establishment process. The supralittoral isopod Ligia exotica has a wide tropical
      and subtropical distribution, frequently found in harbors and ports around the
      globe. This isopod is hypothesized to have an Old World origin, from where it was
      unintentionally introduced to other regions via wooden ships and solid ballast.
      Its native range, however, remains uncertain. Recent molecular studies uncovered
      the presence of two highly divergent lineages of L. exotica in East Asia, and
      suggest this region is a source of nonindigenous populations. In this study, we
      conducted phylogenetic analyses (Maximum Likelihood and Bayesian) of a fragment
      of the mitochondrial 16S ribosomal (r)DNA gene using a dataset of this isopod
      that greatly expanded previous representation from Asia and putative
      nonindigenous populations around the world. For a subset of samples, sequences of
      12S rDNA and NaK were also obtained and analyzed together with 16S rDNA. Our
      results show that L. exotica is comprised of several highly divergent genetic
      lineages, which probably represent different species. Most of the 16S rDNA
      genetic diversity (48 haplotypes) was detected in East and Southeast Asia. Only
      seven haplotypes were observed outside this region (in the Americas, Hawai'i,
      Africa and India), which were identical or closely related to haplotypes found in
      East and Southeast Asia. Phylogenetic patterns indicate the L. exotica clade
      originated and diversified in East and Southeast Asia, and only members of one of
      the divergent lineages have spread out of this region, recently, suggesting the
      potential to become invasive is phylogenetically constrained.

PMID- 29576935
TI  - Homology modeling and docking studies of a Delta9-fatty acid desaturase from a
      Cold-tolerant Pseudomonas sp. AMS8.
AB  - Membrane-bound fatty acid desaturases perform oxygenated desaturation reactions
      to insert double bonds within fatty acyl chains in regioselective and
      stereoselective manners. The Delta9-fatty acid desaturase strictly creates the
      first double bond between C9 and 10 positions of most saturated substrates. As
      the three-dimensional structures of the bacterial membrane fatty acid desaturases
      are not available, relevant information about the enzymes are derived from their
      amino acid sequences, site-directed mutagenesis and domain swapping in similar
      membrane-bound desaturases. The cold-tolerant Pseudomonas sp. AMS8 was found to
      produce high amount of monounsaturated fatty acids at low temperature.
      Subsequently, an active Delta9-fatty acid desaturase was isolated and
      functionally expressed in Escherichia coli. In this paper we report homology
      modeling and docking studies of a Delta9-fatty acid desaturase from a Cold
      tolerant Pseudomonas sp. AMS8 for the first time to the best of our knowledge.
      Three dimensional structure of the enzyme was built using MODELLER version 9.18
      using a suitable template. The protein model contained the three conserved
      histidine residues typical for all membrane-bound desaturase catalytic activity.
      The structure was subjected to energy minimization and checked for correctness
      using Ramachandran plots and ERRAT, which showed a good quality model of 91.6 and
      65.0%, respectively. The protein model was used to preform MD simulation and
      docking of palmitic acid using CHARMM36 force field in GROMACS Version 5 and
      Autodock tool Version 4.2, respectively. The docking simulation with the lowest
      binding energy, -6.8 kcal/mol had a number of residues in close contact with the
      docked palmitic acid namely, Ile26, Tyr95, Val179, Gly180, Pro64, Glu203, His34,
      His206, His71, Arg182, Thr85, Lys98 and His177. Interestingly, among the binding
      residues are His34, His71 and His206 from the first, second, and third conserved
      histidine motif, respectively, which constitute the active site of the enzyme.
      The results obtained are in compliance with the in vivo activity of the Delta9
      fatty acid desaturase on the membrane phospholipids.

PMID- 29576936
TI  - Biosynthesis of silver nanoparticles using Caesalpinia ferrea (Tul.) Martius
      extract: physicochemical characterization, antifungal activity and cytotoxicity.
AB  - Background: Green synthesis is an ecological technique for the production of well
      characterized metallic nanoparticles using plants. This study investigated the
      synthesis of silver nanoparticles (AgNPs) using a Caesalpinia ferrea seed extract
      as a reducing agent. Methods: The formation of AgNPs was identified by
      instrumental analysis, including ultraviolet-visible (UV-Vis) spectroscopy,
      scanning electron microscopy (SEM), X-ray diffraction (XRD) of the AgNPs, and
      surface-enhanced Raman scattering (SERS) spectra of rhodamine-6G (R6G). We
      studied the physicochemical characterization of AgNPs, evaluated them as an
      antifungal agent against Candida albicans, Candida kruzei, Candida glabrata and
      Candida guilliermondii, and estimated their minimum inhibitory concentration
      (MIC) and minimum fungicidal concentration (MFC) values. Lastly, this study
      evaluated the cytotoxicity of the AgNPs in murine L929 fibroblasts cells using an
      MTT assay. Results: The UV-Vis spectroscopy, SERS, SEM and XRD results confirmed
      the rapid formation of spheroidal 30-50 nm AgNPs. The MIC and MFC values
      indicated the antifungal potential of AgNPs against most of the fungi studied and
      high cell viability in murine L929 fibroblasts. In addition, this study
      demonstrated that C. ferrea seed extracts may be used for the green synthesis of
      AgNPs at room temperature for the treatment of candidiasis.

PMID- 29576937
TI  - Phylogenetic surveys on the newt genus Tylototriton sensu lato (Salamandridae,
      Caudata) reveal cryptic diversity and novel diversification promoted by
      historical climatic shifts.
AB  - Global climatic transitions and Tibetan Plateau uplifts are hypothesized to have
      profoundly impacted biodiversity in southeastern Asia. To further test the
      hypotheses related to the impacts of these incidents, we investigated the
      diversification patterns of the newt genus Tylototriton sensu lato, distributed
      across the mountain ranges of southeastern Asia. Gene-tree and species-tree
      analyses of two mitochondrial genes and two nuclear genes revealed five major
      clades in the genus, and suggested several cryptic species. Dating estimates
      suggested that the genus originated in the early-to-middle Miocene. Under
      different species delimitating scenarios, diversification analyses with birth
      death likelihood tests indicated that the genus held a higher diversification
      rate in the late Miocene-to-Pliocene era than that in the Pleistocene. Ancestral
      area reconstructions indicated that the genus originated from the northern
      Indochina Peninsula. Accordingly, we hypothesized that the Miocene Climatic
      Transition triggered the diversification of the genus, and the reinforcement of
      East Asian monsoons associated with the stepwise uplifts of the Tibetan Plateau
      promoted the radiation of the genus in southeastern Asia during the Miocene-to
      Pliocene period. Quaternary glacial cycles likely had limited effects on
      speciation events in the genus, but mainly had contributions on their
      intraspecific differentiations.

PMID- 29576938
TI  - Evolutionary persistence in Gunnera and the contribution of southern plant groups
      to the tropical Andes biodiversity hotspot.
AB  - Several studies have demonstrated the contribution of northern immigrants to the
      flora of the tropical Andes-the world's richest and most diverse biodiversity
      hotspot. However, much less is known about the biogeographic history and
      diversification of Andean groups with southern origins, although it has been
      suggested that northern and southern groups have contributed roughly equally to
      the high Andean (i.e., paramo) flora. Here we infer the evolutionary history of
      the southern hemisphere plant genus Gunnera, a lineage with a rich fossil history
      and an important ecological role as an early colonising species characteristic of
      wet, montane environments. Our results show striking contrasts in species
      diversification, where some species may have persisted for some 90 million years,
      and whereas others date to less than 2 Ma since origination. The outstanding
      longevity of the group is likely linked to a high degree of niche conservatism
      across its highly disjunct range, whereby Gunnera tracks damp and boggy soils in
      cool habitats. Colonisation of the northern Andes is related to Quaternary
      climate change, with subsequent rapid diversification appearing to be driven by
      their ability to take advantage of environmental opportunities. This study
      demonstrates the composite origin of a mega-diverse biota.

PMID- 29576939
TI  - Detection of linear features including bone and skin areas in ultrasound images
      of joints.
AB  - Identifying the separate parts in ultrasound images such as bone and skin plays a
      crucial role in the synovitis detection task. This paper presents a detector of
      bone and skin regions in the form of a classifier which is trained on a set of
      annotated images. Selected regions have labels: skin or bone or none. Feature
      vectors used by the classifier are assigned to image pixels as a result of
      passing the image through the bank of linear and nonlinear filters. The filters
      include Gaussian blurring filter, its first and second order derivatives,
      Laplacian as well as positive and negative threshold operations applied to the
      filtered images. We compared multiple supervised learning classifiers including
      Naive Bayes, k-Nearest Neighbour, Decision Trees, Random Forest, AdaBoost and
      Support Vector Machines (SVM) with various kernels, using four classification
      performance scores and computation time. The Random Forest classifier was
      selected for the final use, as it gives the best overall evaluation results.

PMID- 29576940
TI  - Fuel-cell breathalyser use for field research on alcohol intoxication: an
      independent psychometric evaluation.
AB  - Background: Several field studies have used fuel-cell breathalysers (FCB) to
      investigate the prevalence of alcohol intoxication. However, there is a lack of
      evidence evaluating the psychometric properties of these breathalysers outside of
      the forensic disciplines. Methods: The current research describes four studies
      designed that assess the reliability and validity of portable platinum FCBs for
      research on alcohol intoxication. Utilising the Alcolizer LE5 breathalyser and,
      to a lesser degree, the Lifeloc FC-20 and the Lion Intoxilyzer 8000, each study
      sampled patrons frequenting popular night-time entertainment districts with
      varying levels of alcohol intoxication. Results: Study one and two found
      excellent test-retest reliability and inter-instrument reliability for FCBs.
      Study three and four provided evidence to support the convergent validity of the
      two FCBs (the LE5 with the FC20), and with an evidential breathalyser (i.e., the
      Lion Intoxilyzer 8000; EB). Discussion: A 93-97% agreement rate between
      breathalyser readings was found across the four studies. Portable FCB are
      recommended as a reliable and valid instrument for research designs requiring
      quick alcohol intoxication estimations in large populations. Strategies to
      enhance reliable and valid readings are provided for field researchers.

PMID- 29576941
TI  - Tobacco rattle virus-induced PHYTOENE DESATURASE (PDS) and Mg-chelatase H subunit
      (ChlH) gene silencing in Solanum pseudocapsicum L.
AB  - Virus-induced gene silencing (VIGS) is an attractive tool for determining gene
      function in plants. The present study constitutes the first application of VIGS
      in S. pseudocapsicum, which has great ornamental and pharmaceutical value, using
      tobacco rattle virus (TRV) vectors. Two marker genes, PHYTOENE DESATURASE (PDS)
      and Mg-chelatase H subunit (ChlH), were used to test the VIGS system in S.
      pseudocapsicum. The photobleaching and yellow-leaf phenotypes of the silenced
      plants were shown to significantly correlate with the down-regulation of
      endogenous SpPDS and SpChlH, respectively (P <= 0.05). Moreover, the parameters
      potentially affecting the efficiency of VIGS in S. pseudocapsicum, including the
      Agrobacterium strain and the inoculation method (leaf syringe-infiltration,
      sprout vacuum-infiltration and seed vacuum-infiltration), were compared. The
      optimized VIGS parameters were the leaf syringe-infiltration method, the
      Agrobacterium strain GV3101 and the growth of agro-inoculated plants at 25
      degrees . With these parameters, the silencing efficiency of SpPDS and SpChlH
      could reach approximately 50% in S. pseudocapsicum. Additionally, the suitability
      of various reference genes was screened by RT-qPCR using three candidate genes,
      and the results demonstrated that glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH) can serve as a suitable reference for assessing the gene expression
      levels of VIGS systems in S. pseudocapsicum. The proven application of VIGS in S.
      pseudocapsicum and the characterization of a suitable reference gene in the
      present work will expedite the functional characterization of novel genes in S.
      pseudocapsicum.

PMID- 29576942
TI  - Spatial-temporal trend for mother-to-child transmission of HIV up to infancy and
      during pre-Option B+ in western Kenya, 2007-13.
AB  - Introduction: Using spatial-temporal analyses to understand coverage and trends
      in elimination of mother-to-child transmission of HIV (e-MTCT) efforts may be
      helpful in ensuring timely services are delivered to the right place. We present
      spatial-temporal analysis of seven years of HIV early infant diagnosis (EID) data
      collected from 12 districts in western Kenya from January 2007 to November 2013,
      during pre-Option B+ use. Methods: We included in the analysis infants up to one
      year old. We performed trend analysis using extended Cochran-Mantel-Haenszel
      stratified test and logistic regression models to examine trends and associations
      of infant HIV status at first diagnosis with: early diagnosis (<8 weeks after
      birth), age at specimen collection, infant ever having breastfed, use of single
      dose nevirapine, and maternal antiretroviral therapy status. We examined these
      covariates and fitted spatial and spatial-temporal semiparametric Poisson
      regression models to explain HIV-infection rates using R-integrated nested
      Laplace approximation package. We calculated new infections per 100,000 live
      births and used Quantum GIS to map fitted MTCT estimates for each district in
      Nyanza region. Results: Median age was two months, interquartile range 1.5-5.8
      months. Unadjusted pooled positive rate was 11.8% in the seven-years period and
      declined from 19.7% in 2007 to 7.0% in 2013, p < 0.01. Uptake of testing <=8
      weeks after birth was under 50% in 2007 and increased to 64.1% by 2013, p < 0.01.
      By 2013, the overall standardized MTCT rate was 447 infections per 100,000 live
      births. Based on Bayesian deviance information criterion comparisons, the spatial
      temporal model with maternal and infant covariates was best in explaining
      geographical variation in MTCT. Discussion: Improved EID uptake and reduced MTCT
      rates are indicators of progress towards e-MTCT. Cojoined analysis of time and
      covariates in a spatial context provides a robust approach for explaining
      differences in programmatic impact over time. Conclusion: During this pre-Option
      B+ period, the prevention of mother to child transmission program in this region
      has not achieved e-MTCT target of <=50 infections per 100,000 live births.
      Geographical disparities in program achievements may signify gaps in spatial
      distribution of e-MTCT efforts and could indicate areas needing further resources
      and interventions.

PMID- 29576943
TI  - Molecular cloning and expression analysis of three ThERFs involved in the
      response to waterlogging stress of Taxodium 'Zhongshanshan406', and subcellular
      localization of the gene products.
AB  - As a subfamily of the APETALA 2/ethylene response element binding protein
      (AP2/EREBP) transcription factor superfamily, the ethylene response factor (ERF)
      is widely involved in the regulation of growth and response to various abiotic
      stresses in plants, and has been shown to be the main transcription factor
      regulating transcription of the genes related to hypoxia and waterlogging stress.
      In this study, three ThERF genes, with significant differences in expression
      profile in response to flooding stress, were identified from the transcriptomics
      data acquired from Taxodium hybrid 'Zhongshanshan 406' (T. mucronatum Tenore * T.
      distichum (L.) Rich) under waterlogging stress: ThERF15, ThERF39 and ThRAP2.3
      (GenBank ID: KY463467, KY463468 and KY463470, respectively).The full-length cDNA
      of each of the three ERFs was obtained using the RACE (rapid amplification cDNA
      ends) method, and all three were intron-free. Multiple protein sequence
      alignments indicated that ThERF15, ThERF39 and ThRAP2.3 proteins all had only one
      AP2-ERF domain and belonged to the ERF subfamily. A transient gene expression
      assay demonstrated that ThERF15, ThERF39 and ThRAP2.3 were all localized to the
      nucleus. Real-time quantitative PCR (qPCR) revealed that the expression of
      ThERF15, ThERF39 and ThRAP2.3 exhibited significant differences, compared with
      the control, in response to two levels of flooding treatment (half-flooding or
      total-submergence) of 'Zhongshanshan 406'. Quantification of ethylene
      concentration revealed that ethylene was more relevant to the level of expression
      than the period of flooding treatment. Based on the experimental results above,
      ThERF15, ThERF39 and ThRAP2.3 were identified as being related to the regulation
      of downstream flooding- responsive gene expression in 'Zhongshanshan 406'.
      ThRAP2.3 is most likely to be a key downstream-response ERF gene to respond to
      the output of the ethylene signal generated by flooding stress.

PMID- 29576944
TI  - The impact of different agroecological conditions on the nutritional composition
      of quinoa seeds.
AB  - Quinoa cultivation has been expanded around the world in the last decade and is
      considered an exceptional crop with the potential of contributing to food
      security worldwide. The exceptional nutritional value of quinoa seeds relies on
      their high protein content, their amino acid profile that includes a good balance
      of essential amino acids, the mineral composition and the presence of
      antioxidants and other important nutrients such as fiber or vitamins. Although
      several studies have pointed to the influence of different environmental stresses
      in certain nutritional components little attention has been paid to the effect of
      the agroecological context on the nutritional properties of the seeds what may
      strongly impact on the consumer food's quality. Thus, aiming to evaluate the
      effect of the agroecological conditions on the nutritional profile of quinoa
      seeds we analyzed three quinoa cultivars (Salcedo-INIA, Titicaca and Regalona) at
      different locations (Spain, Peru and Chile). The results revealed that several
      nutritional parameters such as the amino acid profile, the protein content, the
      mineral composition and the phytate amount in the seeds depend on the location
      and cultivar while other parameters such as saponin or fiber were more stable
      across locations. Our results support the notion that nutritional characteristics
      of seeds may be determined by seed's origin and further analysis are needed to
      define the exact mechanisms that control the changes in the seeds nutritional
      properties.

PMID- 29576945
TI  - Establishment and quality evaluation of a glioma biobank in Beijing Tiantan
      Hospital.
AB  - Background: We established a glioma biobank at Beijing Tiantan Hospital in
      November, 2010. Specialized residents have been trained to collect, store and
      manage the biobank in accordance with standard operating procedures. Methods: One
      hundred samples were selected to evaluate the quality of glioma samples stored in
      the liquid nitrogen tank during different periods (from 2011 to 2015) by
      morphological examination, RNA integrity determination, DNA integrity
      determination and housekeeping gene expression determination. Results: The
      majority of samples (95%) had high RNA quality for further analysis with RIN >=6.
      Quality of DNA of all samples were stable without significant degradation.
      Conclusion: Storage conditions of our biobank are suitable for long-term (at
      least five years) sample preservation with high molecular quality.

PMID- 29576946
TI  - Difficulties when using video playback to investigate social cognition in
      California scrub-jays (Aphelocoma californica).
AB  - Previous research has suggested that videos can be used to experimentally
      manipulate social stimuli. In the present study, we used the California scrub
      jays' cache protection strategies to assess whether video playback can be used to
      simulate conspecifics in a social context. In both the lab and the field, scrub
      jays are known to exhibit a range of behaviours to protect their caches from
      potential pilferage by a conspecific, for example by hiding food in locations out
      of the observer's view or by re-caching previously made caches once the observer
      has left. Here, we presented scrub-jays with videos of a conspecific observer as
      well as two non-social conditions during a caching period and assessed whether
      they would cache out of the observer's "view" (Experiment 1) or would re-cache
      their caches once the observer was no longer present (Experiment 2). In contrast
      to previous studies using live observers, the scrub-jays' caching and re-caching
      behaviour was not influenced by whether the observer was present or absent. These
      findings suggest that there might be limitations in using video playback of
      social agents to mimic real-life situations when investigating corvid decision
      making.

PMID- 29576947
TI  - Characterization of shifts of koala (Phascolarctos cinereus) intestinal microbial
      communities associated with antibiotic treatment.
AB  - Koalas (Phascolarctos cinereus) are arboreal marsupials native to Australia that
      eat a specialized diet of almost exclusively eucalyptus leaves. Microbes in koala
      intestines are known to break down otherwise toxic compounds, such as tannins, in
      eucalyptus leaves. Infections by Chlamydia, obligate intracellular bacterial
      pathogens, are highly prevalent in koala populations. If animals with Chlamydia
      infections are received by wildlife hospitals, a range of antibiotics can be used
      to treat them. However, previous studies suggested that koalas can suffer adverse
      side effects during antibiotic treatment. This study aimed to use 16S rRNA gene
      sequences derived from koala feces to characterize the intestinal microbiome of
      koalas throughout antibiotic treatment and identify specific taxa associated with
      koala health after treatment. Although differences in the alpha diversity were
      observed in the intestinal flora between treated and untreated koalas and between
      koalas treated with different antibiotics, these differences were not
      statistically significant. The alpha diversity of microbial communities from
      koalas that lived through antibiotic treatment versus those who did not was
      significantly greater, however. Beta diversity analysis largely confirmed the
      latter observation, revealing that the overall communities were different between
      koalas on antibiotics that died versus those that survived or never received
      antibiotics. Using both machine learning and OTU (operational taxonomic unit) co
      occurrence network analyses, we found that OTUs that are very closely related to
      Lonepinella koalarum, a known tannin degrader found by culture-based methods to
      be present in koala intestines, was correlated with a koala's health status. This
      is the first study to characterize the time course of effects of antibiotics on
      koala intestinal microbiomes. Our results suggest it may be useful to pursue
      alternative treatments for Chlamydia infections without the use of antibiotics or
      the development of Chlamydia-specific antimicrobial compounds that do not broadly
      affect microbial communities.

PMID- 29576948
TI  - Characterization of the salivary microbiome in people with obesity.
AB  - Background: The interactions between the gut microbiome and obesity have been
      extensively studied. Although the oral cavity is the gateway to the gut, and is
      extensively colonized with microbes, little is known about the oral microbiome in
      people with obesity. In the present study, we investigated the salivary
      microbiome in obese and normal weight healthy participants using metagenomic
      analysis. The subjects were categorized into two groups, obesity and normal
      weight, based on their BMIs. Methods: We characterized the salivary microbiome of
      33 adults with obesity and 29 normal weight controls using high-throughput
      sequencing of the V3-V4 region of the 16S rRNA gene (Illumina MiSeq). None of the
      selected participants had systemic, oral mucosal, or periodontal diseases.
      Results: The salivary microbiome of the obesity group was distinct from that of
      the normal weight group. The salivary microbiome of periodontally healthy people
      with obesity had both significantly lower bacterial diversity and richness
      compared with the controls. The genus Prevotella, Granulicatella,
      Peptostreptococcus, Solobacterium, Catonella, and Mogibacterium were
      significantly more abundant in the obesity group; meanwhile the genus
      Haemophilus, Corynebacterium, Capnocytophaga, and Staphylococcus were less
      abundant in the obesity group. We also performed a functional analysis of the
      inferred metagenomes, and showed that the salivary community associated with
      obesity had a stronger signature of immune disease and a decreased functional
      signature related to environmental adaptation and Xenobiotics biodegradation
      compared with the normal weight controls. Discussion: Our study demonstrates that
      the microbial diversity and structure of the salivary microbiome in people with
      obesity are significantly different from those of normal weight controls. These
      results suggested that changes in the structure and function of salivary
      microbiome in people with obesity might reflect their susceptibility to oral
      diseases.

PMID- 29576950
TI  - Assessing the disturbance potential of small unoccupied aircraft systems (UAS) on
      gray seals (Halichoerus grypus) at breeding colonies in Nova Scotia, Canada.
AB  - The use of small unoccupied aircraft systems (UAS) for ecological studies and
      wildlife population assessments is increasing. These methods can provide
      significant benefits in terms of costs and reductions in human risk, but little
      is known if UAS-based approaches cause disturbance of animals during operations.
      To address this knowledge gap, we conducted a series of UAS flights at gray seal
      breeding colonies on Hay and Saddle Islands in Nova Scotia, Canada. Using a small
      fixed-wing UAS, we assessed both immediate and short-term effects of surveys
      using sequential image analysis and between-flight seal counts in ten, 50 m2
      random quadrats at each colony. Counts of adult gray seals and young-of-the-year
      animals between first and second flights revealed no changes in abundance in
      quadrats (matched pair t-test p > 0.69) and slopes approaching 1 for linear
      regression comparisons (r2 > 0.80). Sequential image analysis revealed no changes
      in orientation or posture of imaged animals. We also assessed the acoustic
      properties of the small UAS in relation to low ambient noise conditions using
      sound equivalent level (Leq) measurements with a calibrated U-MIK 1 and a 1/3
      octave band soundscape approach. The results of Leq measurements indicate that
      small fixed-wing UAS are quiet, with most energy above 160 Hz, and that levels
      across 1/3 octave bands do not greatly exceed ambient acoustic measurements in a
      quiet field during operations at standard survey altitudes. As such, this
      platform is unlikely to acoustically disturb gray seals at breeding colonies
      during population surveys. The results of the present study indicate that the
      effects of small fixed-wing UAS on gray seals at breeding colonies are
      negligible, and that fixed-wing UAS-based approaches should be considered amongst
      best practices for assessing gray seal colonies.

PMID- 29576949
TI  - An overview on the interplay between nutraceuticals and gut microbiota.
AB  - Background: Nowadays, growing attention was being given to the alternative ways
      to prevent or treat diseases. Nutraceuticals are used increasingly for this
      purpose. Many of these are being used as alternative therapy. Classic therapy
      with synthetic drugs, although very effective, has many side effects. The term
      "nutraceuticals" refers to the link between the nutritional and pharmaceutical
      domains. Also, lately, many studies have been done to investigate the role of
      microbiota in maintaining health. There is the hypothesis that some of the health
      benefits of nutraceuticals are due to their ability to change the microbiota. The
      aim of this review was to emphasize the link between the most commonly used
      nutraceuticals, the microbiota and the health benefits. Methods: We selected the
      articles in PubMed, published up to July 2017, that provided information about
      most used nutraceuticals, microbiota and health benefits. In this review, we
      incorporate evidence from various types of studies, including observational, in
      vitro and in vivo, clinical studies or animal experiments. Results: The results
      demonstrate that many nutraceuticals change the composition of microbiota and can
      interfere with health status of the patients. Discussion: There is evidence which
      sustains the importance of nutraceuticals in people's health through microbiota
      but further studies are needed to complete the assessment of nutraceuticals in
      health benefit as a consequence of microbiota's changing.

PMID- 29576951
TI  - Change in skeletal muscle stiffness after running competition is dependent on
      both running distance and recovery time: a pilot study.
AB  - Long-distance running competitions impose a large amount of mechanical loading
      and strain leading to muscle edema and delayed onset muscle soreness (DOMS).
      Damage to various muscle fibers, metabolic impairments and fatigue have been
      linked to explain how DOMS impairs muscle function. Disruptions of muscle fiber
      during DOMS exacerbated by exercise have been shown to change muscle mechanical
      properties. The objective of this study is to quantify changes in mechanical
      properties of different muscles in the thigh and lower leg as function of running
      distance and time after competition. A custom implementation of Focused Comb-Push
      Ultrasound Shear Elastography (F-CUSE) method was used to evaluate shear modulus
      in runners before and after a race. Twenty-two healthy individuals (age: 23 +/- 5
      years) were recruited using convenience sampling and split into three race
      categories: short distance (nine subjects, 3-5 miles), middle distance (10
      subjects, 10-13 miles), and long distance (three subjects, 26+ miles). Shear Wave
      Elastography (SWE) measurements were taken on both legs of each subject on the
      rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), soleus, lateral
      gastrocnemius (LG), medial gastrocnemius (MG), biceps femoris (BF) and
      semitendinosus (ST) muscles. For statistical analyses, a linear mixed model was
      used, with recovery time and running distance as fixed variables, while shear
      modulus was used as the dependent variable. Recovery time had a significant
      effect on the soleus (p = 0.05), while running distance had considerable effect
      on the biceps femoris (p = 0.02), vastus lateralis (p < 0.01) and semitendinosus
      muscles (p = 0.02). Sixty-seven percent of muscles exhibited a decreasing
      stiffness trend from before competition to immediately after competition. The
      preliminary results suggest that SWE could potentially be used to quantify
      changes of muscle mechanical properties as a way for measuring recovery
      procedures for runners.

PMID- 29576953
TI  - pcr: an R package for quality assessment, analysis and testing of qPCR data.
AB  - Background: Real-time quantitative PCR (qPCR) is a broadly used technique in the
      biomedical research. Currently, few different analysis models are used to
      determine the quality of data and to quantify the mRNA level across the
      experimental conditions. Methods: We developed an R package to implement methods
      for quality assessment, analysis and testing qPCR data for statistical
      significance. Double Delta CT and standard curve models were implemented to
      quantify the relative expression of target genes from CT in standard qPCR control
      group experiments. In addition, calculation of amplification efficiency and
      curves from serial dilution qPCR experiments are used to assess the quality of
      the data. Finally, two-group testing and linear models were used to test for
      significance of the difference in expression control groups and conditions of
      interest. Results: Using two datasets from qPCR experiments, we applied different
      quality assessment, analysis and statistical testing in the pcr package and
      compared the results to the original published articles. The final relative
      expression values from the different models, as well as the intermediary outputs,
      were checked against the expected results in the original papers and were found
      to be accurate and reliable. Conclusion: The pcr package provides an intuitive
      and unified interface for its main functions to allow biologist to perform all
      necessary steps of qPCR analysis and produce graphs in a uniform way.

PMID- 29576952
TI  - Squeezing water from a stone: high-throughput sequencing from a 145-year old
      holotype resolves (barely) a cryptic species problem in flying lizards.
AB  - We used Massively Parallel High-Throughput Sequencing to obtain genetic data from
      a 145-year old holotype specimen of the flying lizard, Draco cristatellus.
      Obtaining genetic data from this holotype was necessary to resolve an otherwise
      intractable taxonomic problem involving the status of this species relative to
      closely related sympatric Draco species that cannot otherwise be distinguished
      from one another on the basis of museum specimens. Initial analyses suggested
      that the DNA present in the holotype sample was so degraded as to be unusable for
      sequencing. However, we used a specialized extraction procedure developed for
      highly degraded ancient DNA samples and MiSeq shotgun sequencing to obtain just
      enough low-coverage mitochondrial DNA (721 base pairs) to conclusively resolve
      the species status of the holotype as well as a second known specimen of this
      species. The holotype was prepared before the advent of formalin-fixation and
      therefore was most likely originally fixed with ethanol and never exposed to
      formalin. Whereas conventional wisdom suggests that formalin-fixed samples should
      be the most challenging for DNA sequencing, we propose that evaporation during
      long-term alcohol storage and consequent water-exposure may subject older ethanol
      fixed museum specimens to hydrolytic damage. If so, this may pose an even greater
      challenge for sequencing efforts involving historical samples.

PMID- 29576954
TI  - A comparative modeling study on non-climatic and climatic risk assessment on
      Asian Tiger Mosquito (Aedes albopictus).
AB  - Aedes albopictus, the Asian Tiger Mosquito, vector of Chikungunya, Dengue Fever
      and Zika viruses, has proven its hardy adaptability in expansion from its natural
      Asian, forest edge, tree hole habitat on the back of international trade
      transportation, re-establishing in temperate urban surrounds, in a range of water
      receptacles and semi-enclosures of organic matter. Conventional aerial spray
      mosquito vector controls focus on wetland and stagnant water expanses, proven to
      miss the protected hollows and crevices favoured by Ae. albopictus. New control
      or eradication strategies are thus essential, particular in light of potential
      expansions in the southeastern and eastern USA. Successful regional vector
      control strategies require risk level analysis. Should strategies prioritize
      regions with non-climatic or climatic suitability parameters for Ae. albopictus?
      Our study used current Ae. albopictus distribution data to develop two
      independent models: (i) regions with suitable non-climatic factors, and (ii)
      regions with suitable climate for Ae. albopictus in southeastern USA. Non
      climatic model processing used Evidential Belief Function (EBF), together with
      six geographical conditioning factors (raster data layers), to establish the
      probability index. Validation of the analysis results was estimated with area
      under the curve (AUC) using Ae. albopictus presence data. Climatic modeling was
      based on two General Circulation Models (GCMs), Miroc3.2 and CSIRO-MK30 running
      the RCP 8.5 scenario in MaxEnt software. EBF non-climatic model results achieved
      a 0.70 prediction rate and 0.73 success rate, confirming suitability of the study
      site regions for Ae. albopictus establishment. The climatic model results showed
      the best-fit model comprised Coldest Quarter Mean Temp, Precipitation of Wettest
      Quarter and Driest Quarter Precipitation factors with mean AUC value of 0.86.
      Both GCMs showed that the whole study site is highly suitable and will remain
      suitable climatically, according to the prediction for 2055, for Ae. albopictus
      expansion.

PMID- 29576955
TI  - Measuring short distance dispersal of Alliaria petiolata and determining
      potential long distance dispersal mechanisms.
AB  - Introduction: Alliaria petiolata, an herbaceous plant, has invaded woodlands in
      North America. Its ecology has been thoroughly studied, but an overlooked aspect
      of its biology is seed dispersal distances and mechanisms. We measured seed
      dispersal distances in the field and tested if epizoochory is a potential
      mechanism for long-distance seed dispersal. Methods: Dispersal distances were
      measured by placing seed traps in a sector design around three seed point
      sources, which consisted of 15 second-year plants transplanted within a 0.25 m
      radius circle. Traps were placed at intervals ranging from 0.25-3.25 m from the
      point source. Traps remained in the field until a majority of seeds were
      dispersed. Eight probability density functions were fitted to seed trap counts
      via maximum likelihood. Epizoochory was tested as a potential seed dispersal
      mechanism for A. petiolata through a combination of field and laboratory
      experiments. To test if small mammals transport A. petiolata seeds in their fur,
      experimental blocks were placed around dense A. petiolata patches. Each block
      contained a mammal inclusion treatment (MIT) and control. The MIT consisted of a
      wood-frame (31 * 61* 31 cm) covered in wire mesh, except for the two 31 * 31 cm
      ends, placed over a germination tray filled with potting soil. A pan filled with
      bait was placed in the center of the tray. The control frame (11 * 31 * 61 cm)
      was placed over a germination tray and completely covered in wire mesh to exclude
      animal activity. Treatments were in the field for peak seed dispersal. In March,
      trays were moved to a greenhouse and A. petiolata seedlings were counted and then
      compared between treatments. To determine if A. petiolata seeds attach to raccoon
      (Procyon lotor) and white-tailed deer (Odocoileus virginianus) fur, wet and dry
      seeds were dropped onto wet and dry fur. Furs were rotated 180 degrees and the
      seeds that remained attached were counted. To measure seed retention, seeds were
      dropped on furs and rotated as before, then the furs were agitated for one hour.
      The seeds retained in the fur were counted. Results: For the seed dispersal
      experiment, the 2Dt function provided the best fit and was the most biologically
      meaningful. It predicted that seed density rapidly declined with distance from
      the point source. Mean dispersal distance was 0.52 m and 95% of seeds dispersed
      within 1.14 m. The epizoochory field experiment showed increased mammal activity
      and A. petiolata seedlings in germination trays of the MIT compared to control.
      Laboratory studies showed 3-26% of seeds were attached and retained by raccoon
      and deer fur. Retention significantly increased if either seed or fur were wet
      (57-98%). Discussion: Without animal seed vectors, most seeds fall within a short
      distance of the seed source; however, long distance dispersal may be accomplished
      by epizoochory. Our data are consistent with A. petiolata's widespread
      distribution and development of dense clusters of the species in invaded areas.

PMID- 29576956
TI  - Phylogeographic structure in three North American tent caterpillar species
      (Lepidoptera: Lasiocampidae): Malacosoma americana, M. californica, and M.
      disstria.
AB  - While phylogeographic structure has been examined in many North American
      vertebrate species, insects have received much less attention despite their
      central ecological roles. The moth genus Malacosoma (Hubner, 1820), is an
      important group of forestry pests responsible for large-scale defoliation across
      much of the Nearctic and Palearctic. The present study uses sequence variation in
      the mitochondrial cytochrome c oxidase 1 (COI) gene to examine the population
      genetic structure of the three widespread Malacosoma species (M. americana, M.
      californica, and M. disstria). Populations of all three species showed highest
      diversity in the south, suggesting that modern populations derived from southern
      refugia with loss of variation as these lineages dispersed northwards. However,
      despite similar life histories and dispersal abilities, the extent of regional
      variation varied among the taxa. M. americana, a species restricted to eastern
      North America, showed much less genetic structure than the western M. californica
      or the widespread M. disstria. The regional differentiation in the latter
      reflects the likely derivation of modern lineages from several refugia, as well
      as taxonomic uncertainty in M. californica. In these respects, the three species
      of Malacosoma share phylogeographic patterns similar to those detected in
      vertebrates which are characterised by greater phylogeographic breaks in the
      western half of the continent and limited structure in the east.

PMID- 29576957
TI  - The anatomy of the foveola reinvestigated.
AB  - Objective: In the foveola of the eye, photoreceptors and Muller cells with a
      unique morphology have been described, but little is known about their 3D
      structure and orientation. Considering that there is an angle-dependent change in
      the foveolar photoreceptor response for the same light beam, known as the Stiles
      Crawford Effect of the first kind (SCE I), which is still not fully understood, a
      detailed analysis of the anatomy of the foveolar cells might help to clarify this
      phenomenon. Methods: Serial semithin and ultrathin sections, and focused ion beam
      (FIB) tomography were prepared from 32 foveolae from monkeys (Macaca
      fascicularis) and humans. Foveolae were also analyzed under the electron
      microscope. Serial sections and FIB analysis were then used to construct 3D
      models of central Muller and photoreceptor cells. In addition, we measured the
      transmission of collimated light under the light microscope at different angles
      after it had passed through human foveae from flat mounted isolated retinae.
      Results: In monkeys, outer segments of central foveolar cones are twice as long
      as those from parafoveal cones and do not run completely parallel to the incident
      light. Unique Muller cells are present in the central foveolae (area of 200 um in
      diameter) of humans and monkeys. Light entering the fovea center, which is
      composed only of cones and Muller cells, at an angle of 0 degrees  causes a very
      bright spot after passing through this area. However, when the angle of the light
      beam is changed to 10 degrees , less light is measured after transpasssing
      through the retina, the foveolar center becomes darker and the SCE-like
      phenomenon is directly visible. Measurements of the intensities of light
      transmission through the central foveola for the incident angles 0 and 10 degrees
      resemble the relative luminance efficiency for narrow light bundles as a
      function of the location where the beam enters the pupil as reported by Stiles
      and Crawford. The effect persisted after carefully brushing away the outer
      segments. Conclusion: We show that unique cones and Muller cells with light fibre
      like properties are present in the center of the fovea. These unique Muller cells
      cause an angle dependent, SCE-like drop in the intensity of light guided through
      the foveola. Outer segments from the foveolar cones of monkeys are not straight.

PMID- 29576958
TI  - Ecosystem functional response across precipitation extremes in a sagebrush
      steppe.
AB  - Background: Precipitation is predicted to become more variable in the western
      United States, meaning years of above and below average precipitation will become
      more common. Periods of extreme precipitation are major drivers of interannual
      variability in ecosystem functioning in water limited communities, but how
      ecosystems respond to these extremes over the long-term may shift with
      precipitation means and variances. Long-term changes in ecosystem functional
      response could reflect compensatory changes in species composition or species
      reaching physiological thresholds at extreme precipitation levels. Methods: We
      conducted a five year precipitation manipulation experiment in a sagebrush steppe
      ecosystem in Idaho, United States. We used drought and irrigation treatments
      (approximately 50% decrease/increase) to investigate whether ecosystem functional
      response remains consistent under sustained high or low precipitation. We
      recorded data on aboveground net primary productivity (ANPP), species abundance,
      and soil moisture. We fit a generalized linear mixed effects model to determine
      if the relationship between ANPP and soil moisture differed among treatments. We
      used nonmetric multidimensional scaling to quantify community composition over
      the five years. Results: Ecosystem functional response, defined as the
      relationship between soil moisture and ANPP, was similar among irrigation and
      control treatments, but the drought treatment had a greater slope than the
      control treatment. However, all estimates for the effect of soil moisture on ANPP
      overlapped zero, indicating the relationship is weak and uncertain regardless of
      treatment. There was also large spatial variation in ANPP within-years, which
      contributes to the uncertainty of the soil moisture effect. Plant community
      composition was remarkably stable over the course of the experiment and did not
      differ among treatments. Discussion: Despite some evidence that ecosystem
      functional response became more sensitive under sustained drought conditions, the
      response of ANPP to soil moisture was consistently weak and community composition
      was stable. The similarity of ecosystem functional responses across treatments
      was not related to compensatory shifts at the plant community level, but instead
      may reflect the insensitivity of the dominant species to soil moisture. These
      species may be successful precisely because they have evolved life history
      strategies that buffer them against precipitation variability.

PMID- 29576959
TI  - The use of nutritional supplements to induce ketosis and reduce symptoms
      associated with keto-induction: a narrative review.
AB  - Background: Adaptation to a ketogenic diet (keto-induction) can cause unpleasant
      symptoms, and this can reduce tolerability of the diet. Several methods have been
      suggested as useful for encouraging entry into nutritional ketosis (NK) and
      reducing symptoms of keto-induction. This paper reviews the scientific literature
      on the effects of these methods on time-to-NK and on symptoms during the keto
      induction phase. Methods: PubMed, Science Direct, CINAHL, MEDLINE, Alt Health
      Watch, Food Science Source and EBSCO Psychology and Behavioural Sciences
      Collection electronic databases were searched online. Various purported ketogenic
      supplements were searched along with the terms "ketogenic diet", "ketogenic",
      "ketosis" and ketonaemia (/ ketonemia). Additionally, author names and reference
      lists were used for further search of the selected papers for related references.
      Results: Evidence, from one mouse study, suggests that leucine doesn't
      significantly increase beta-hydroxybutyrate (BOHB) but the addition of leucine to
      a ketogenic diet in humans, while increasing the protein-to-fat ratio of the
      diet, doesn't reduce ketosis. Animal studies indicate that the short chain fatty
      acids acetic acid and butyric acid, increase ketone body concentrations. However,
      only one study has been performed in humans. This demonstrated that butyric acid
      is more ketogenic than either leucine or an 8-chain monoglyceride. Medium-chain
      triglycerides (MCTs) increase BOHB in a linear, dose-dependent manner, and
      promote both ketonaemia and ketogenesis. Exogenous ketones promote ketonaemia but
      may inhibit ketogenesis. Conclusions: There is a clear ketogenic effect of
      supplemental MCTs; however, it is unclear whether they independently improve time
      to NK and reduce symptoms of keto-induction. There is limited research on the
      potential for other supplements to improve time to NK and reduce symptoms of keto
      induction. Few studies have specifically evaluated symptoms and adverse effects
      of a ketogenic diet during the induction phase. Those that have typically were
      not designed to evaluate these variables as primary outcomes, and thus, more
      research is required to elucidate the role that supplementation might play in
      encouraging ketogenesis, improve time to NK, and reduce symptoms associated with
      keto-induction.

PMID- 29576960
TI  - Effect of fatigue and gender on kinematics and ground reaction forces variables
      in recreational runners.
AB  - The presence of fatigue has been shown to modify running biomechanics. Overall in
      terms of gender, women are at lower risk than men for sustaining running-related
      injuries, although it depends on the factors taken into account. One possible
      reason for these differences in the injury rate and location might be the
      dissimilar running patterns between men and women. The purpose of this study was
      to determine the effect of fatigue and gender on the kinematic and ground
      reaction forces (GRF) parameters in recreational runners. Fifty-seven
      participants (28 males and 29 females) had kinematic and GRF variables measured
      while running at speed of 3.3 m s-1 before and after a fatigue test protocol. The
      fatigue protocol included (1) a running Course-Navette test, (2) running up and
      down a flight of stairs for 5 min, and (3) performance of alternating jumps on a
      step (five sets of 1 minute each with 30 resting seconds between the sets).
      Fatigue decreased dorsiflexion (14.24 +/- 4.98 degrees  in pre-fatigue and 12.65
      +/- 6.21 degrees  in fatigue condition, p < 0.05) at foot strike phase in
      females, and plantar flexion (-19.23 +/- 4.12 degrees  in pre-fatigue and -18.26
      +/- 5.31 degrees  in fatigue condition, p < 0.05) at toe-off phase in males.
      These changes led to a decreased loading rate (88.14 +/- 25.82 BW/s in pre
      fatigue and 83.97 +/- 18.83 BW/s in fatigue condition, p < 0.05) and the impact
      peak in females (1.95 +/- 0.31 BW in pre-fatigue and 1.90 +/- 0.31 BW in fatigue
      condition, p < 0.05), and higher peak propulsive forces in males (-0.26 +/- 0.04
      BW in pre-fatigue and -0.27 +/- 0.05 BW in fatigue condition, p < 0.05) in the
      fatigue condition. It seems that better responses to impact under a fatigue
      condition are observed among women. Further studies should confirm whether these
      changes represent a strategy to optimize shock attenuation, prevent running
      injuries and improve running economy.

PMID- 29576961
TI  - Clinical impact of albumin in advanced head and neck cancer patients with free
      flap reconstruction-a retrospective study.
AB  - Background: Poor nutritional status among patients with advanced stage head and
      neck squamous cell carcinoma (HNSCC) is common. Albumin is a common indicator of
      nutritional status and has been shown to be a predictor of oncological outcomes
      and perioperative morbidity. This study aims to determine the prognostic value of
      the serum albumin level among patients with advanced HNSCC undergoing surgery
      with simultaneous free flap reconstruction. Methods: A total of 233 patients with
      advanced head and neck cancer undergoing tumor resection and immediate
      microvascular free flap reconstruction in a tertiary referral center were
      enrolled retrospectively between January 2009 and December 2011. Statistical
      analyses including Pearson's chi-squared test were used to determine whether
      there was a significant difference between each selected clinical factors and
      postoperative major wound infection. Multiple regression analysis was performed
      to reveal the relationship between postoperative major wound infection and
      clinical factors. Kaplan-Meier curves and multivariate Cox regression were
      applied to analyse survival outcome for overall survival (OS), disease-specific
      survival (DSS) and disease-free survival (DFS). Results: Postoperative serum
      albumin level (p < 0.001) and tumor location were both significantly associated
      with postoperative major wound infection (p = 0.018) in univariate analysis.
      Multiple regression analysis showed a higher risk of postoperative major wound
      infection among patients with postoperative hypoalbuminemia than in their
      counterparts (odds ratio [OR] 9.811, 95% CI [2.288-42.065], p = 0.002). Patients
      with a tumor located over the hypopharynx experienced increased risk of
      postoperative major wound infection (OR 2.591, 95% CI [1.095-6.129], p = 0.030).
      With respect to oncological outcomes, preoperative serum albumin level is a
      significant independent prognostic factor for overall survival (OS), disease
      specific survival (DSS) and disease-free survival (DFS). Conclusions:
      Postoperative hypoalbuminemia is a useful indicator for the development of
      postoperative complications. In addition, preoperative hypoalbuminemia is a
      negative prognostic factor for patients who have undergone tumor excision and
      free flap reconstruction for the advanced stage of HNSCC.

PMID- 29576962
TI  - Chloropid flies (Diptera, Chloropidae) associated with pitcher plants in North
      America.
AB  - We review the taxonomy and ecology of Chloropidae (Diptera) associated with
      pitcher plants (Sarraceniaceae) in North America. Tricimba wheeleri Mlynarek
      sp.n. is described from the pitchers of Sarracenia alata Alph.Wood and S.
      leucophylla Raf. in the southeastern United States (Alabama, Mississippi).
      Aphanotrigonum darlingtoniae (Jones) associated with Darlingtonia californica
      Torr. in northern California is redescribed, including the first description of
      male genitalic characters. A lectotype is designated for A. darlingtoniae.
      Published records of other species of Tricimba Lioy in pitcher plants in North
      America are considered accidental or facultative occurrences; published records
      of Aphanotrigonum Duda as pitcher plant associates in eastern North America are
      probably errors in identification.

PMID- 29576963
TI  - Electroencephalographic modulations during an open- or closed-eyes motor task.
AB  - There is fundamental knowledge that during the resting state cerebral activity
      recorded by electroencephalography (EEG) is strongly modulated by the eyes-closed
      condition compared to the eyes-open condition, especially in the occipital lobe.
      However, little research has demonstrated the influence of the eyes-closed
      condition on the motor cortex, particularly during a self-paced movement. This
      prompted the question: How does the motor cortex activity change between the eyes
      closed and eyes-open conditions? To answer this question, we recorded EEG signals
      from 15 voluntary healthy subjects who performed a simple motor task (i.e., a
      voluntary isometric flexion of the right-hand index) under two conditions: eyes
      closed and eyes-open. Our results confirmed strong modulation in the mu rhythm (7
      13 Hz) with a large event-related desynchronisation. However, no significant
      differences have been observed in the beta band (15-30 Hz). Furthermore, evidence
      suggests that the eyes-closed condition influences the behaviour of subjects.
      This study gives us greater insight into the motor cortex and could also be
      useful in the brain-computer interface (BCI) domain.

PMID- 29576964
TI  - Saccadic inhibition in a guided saccade task.
AB  - The eye movement system reacts very systematically to visual transients that are
      presented during the planning phase of a saccade. About 50 to 70 ms after the
      onset of a transient, the number of saccades that are started decreases, a
      phenomenon that has been termed saccadic inhibition. Saccades started just before
      this time window are hypometric compared to regular saccades, presumably because
      the presentation of the transient stops them in mid-flight. Recent research
      investigating the properties of repeated saccades to fixed locations found that
      these early saccades were additionally faster than expected from the main
      sequence relation, suggesting that a saccadic dead time during which saccades can
      no longer be modified does not exist. The present study investigated the
      properties of saccades to random locations in a guided saccade task. As expected,
      early saccades starting just before the saccadic inhibition dip in frequency were
      hypometric. Their velocity profiles implied that these saccades were actively
      stopped after reaching peak velocity. However, the peak velocities of these
      saccades did not generally deviate from the main sequence relation. The question
      whether an active stop of early saccades is incompatible with the idea of a
      saccadic dead time is open to debate.

PMID- 29576965
TI  - A genome-wide investigation of microsatellite mismatches and the association with
      body mass among bird species.
AB  - Mutation rate is usually found to covary with many life history traits of animals
      such as body mass, which has been readily explained by the higher number of
      mutation opportunities per unit time. Although the precise reason for the pattern
      is not yet clear, to determine the universality of this pattern, we tested
      whether life history traits impact another form of genetic mutation, the motif
      mismatches in microsatellites. Employing published genome sequences from 65 avian
      species, we explored the motif mismatches patterns of microsatellites in birds on
      a genomic level and assessed the relationship between motif mismatches and body
      mass in a phylogenetic context. We found that small-bodied species have a higher
      average mismatches and we suggested that higher heterozygosity in imperfect
      microsatellites lead to the increase of motif mismatches. Our results obtained
      from this study imply that a negative body mass trend in mutation rate may be a
      general pattern of avian molecular evolution.

PMID- 29576966
TI  - Distribution and seasonal differences in Pacific Lamprey and Lampetra spp eDNA
      across 18 Puget Sound watersheds.
AB  - Lampreys have a worldwide distribution, are functionally important to ecological
      communities and serve significant roles in many cultures. In Pacific coast
      drainages of North America, lamprey populations have suffered large declines.
      However, lamprey population status and trends within many areas of this region
      are unknown and such information is needed for advancing conservation goals. We
      developed two quantitative PCR-based, aquatic environmental DNA (eDNA) assays for
      detection of Pacific Lamprey (Entosphenus tridentatus) and Lampetra spp, using
      locked nucleic acids (LNAs) in the probe design. We used these assays to
      characterize the spatial distribution of lamprey in 18 watersheds of Puget Sound,
      Washington, by collecting water samples in spring and fall. Pacific Lamprey and
      Lampetra spp were each detected in 14 watersheds and co-occurred in 10
      watersheds. Lamprey eDNA detection rates were much higher in spring compared to
      fall. Specifically, the Pacific Lamprey eDNA detection rate was 3.5 times higher
      in spring and the Lampetra spp eDNA detection rate was 1.5 times higher in spring
      even though larval lamprey are present in streams year-round. This significant
      finding highlights the importance of seasonality on eDNA detection. Higher stream
      discharge in the fall likely contributed to reduced eDNA detection rates,
      although seasonal life history events may have also contributed. These eDNA
      assays differentiate Pacific Lamprey and Lampetra spp across much of their range
      along the west coast of North America. Sequence analysis indicates the Pacific
      Lamprey assay also targets other Entosphenus spp and indicates the Lampetra spp
      assay may have limited or no capability of detecting Lampetra in some locations
      south of the Columbia River Basin. Nevertheless, these assays will serve as a
      valuable tool for resource managers and have direct application to lamprey
      conservation efforts, such as mapping species distributions, occupancy modeling,
      and monitoring translocations and reintroductions.

PMID- 29576967
TI  - Prognostic value of new-onset right bundle-branch block in acute myocardial
      infarction patients: a systematic review and meta-analysis.
AB  - Background: Patients with acute myocardial infarction (AMI) and bundle-branch
      block have poor prognoses. The new European Society of Cardiology guideline
      suggests a primary percutaneous coronary intervention strategy when persistent
      ischemic symptoms occur in patients with persistent ischemic symptoms and right
      bundle-branch block (RBBB), but the level of evidence is not high. In fact, the
      presence of RBBB may lead to the misdiagnosis of transmural ischemia and mask the
      early diagnosis of ST-elevation myocardial infarction. Moreover, new-onset RBBB
      is occasionally caused by AMI. Our study aims to investigate the prognostic value
      of new-onset RBBB in AMI. Methods and Results: We conducted a meta-analysis of
      studies to evaluate the prognostic value of RBBB in AMI patients. Of 914 primary
      records, five studies and 874 MI patients were included for meta-analysis.
      Compared with previous RBBB, AMI patients with new-onset RBBB had a higher risk
      of long-term mortality (RR, 1.66, 95% CI [1.31-2.09], I2 = 0.0%, p = 0.000, n =
      2), ventricular arrhythmia (RR, 4.86, 95% CI [2.10-11.27], I2 = 0.0%, p = 0.000,
      n = 3), and cardiogenic shock (RR, 2.76, 95% CI [1.66-4.59], I2 = 0.0%, p =
      0.000, n = 3), but a lower risk of heart failure (RR, 0.66, 95% CI [0.52-0.85],
      I2 = 2.50%, p = 0.001, n = 4). Compared with AMI patients with new-onset
      permanent RBBB, patients with new-onset transient RBBB had a lower risk of short
      term mortality (RR, 0.20, 95% CI [0.11-0.37], I2 = 44.1%, p = 0.000, n = 4).
      Conclusion: New-onset RBBB is likely to increase long-term mortality, ventricular
      arrhythmia, and cardiogenic shock, but not heart failure in AMI patients. AMI
      patients with new-onset transient RBBB have a lower risk of short-term mortality
      than those with new-onset permanent RBBB. Revascularization therapies should be
      considered when persistent ischemic symptoms occur in patients with RBBB,
      especially new-onset RBBB.

PMID- 29576968
TI  - Assessing universality of DNA barcoding in geographically isolated selected
      desert medicinal species of Fabaceae and Poaceae.
AB  - In pursuit of developing fast and accurate species-level molecular identification
      methods, we tested six DNA barcodes, namely ITS2, matK, rbcLa, ITS2+matK,
      ITS2+rbcLa, matK+rbcLa and ITS2+matK+rbcLa, for their capacity to identify
      frequently consumed but geographically isolated medicinal species of Fabaceae and
      Poaceae indigenous to the desert of Cholistan. Data were analysed by BLASTn
      sequence similarity, pairwise sequence divergence in TAXONDNA, and phylogenetic
      (neighbour-joining and maximum-likelihood trees) methods. Comparison of six
      barcode regions showed that ITS2 has the highest number of variable sites
      (209/360) for tested Fabaceae and (106/365) Poaceae species, the highest species
      level identification (40%) in BLASTn procedure, distinct DNA barcoding gap, 100%
      correct species identification in BM and BCM functions of TAXONDNA, and clear
      cladding pattern with high nodal support in phylogenetic trees in both families.
      ITS2+matK+rbcLa followed ITS2 in its species-level identification capacity. The
      study was concluded with advocating the DNA barcoding as an effective tool for
      species identification and ITS2 as the best barcode region in identifying
      medicinal species of Fabaceae and Poaceae. Current research has practical
      implementation potential in the fields of pharmaco-vigilance, trade of medicinal
      plants and biodiversity conservation.

PMID- 29576969
TI  - Identification of circularRNAs and their targets in Gossypium under Verticillium
      wilt stress based on RNA-seq.
AB  - Circular RNAs (circRNAs), a class of recently discovered non-coding RNAs, play a
      role in biological and developmental processes. A recent study showed that
      circRNAs exist in plants and play a role in their environmental stress responses.
      However, cotton circRNAs and their role in Verticillium wilt response have not
      been identified up to now. In this study, two CSSLs (chromosome segment
      substitution lines) of G.barbadense introgressed into G. hirsutum, CSSL-1 and
      CSSL-4 (a resistant line and a susceptible line to Verticillium wilt,
      respectively), were inoculated with V. dahliae for RNA-seq library construction
      and circRNA analysis. A total of 686 novel circRNAs were identified. CSSL-1 and
      CSSL-4 had similar numbers of circRNAs and shared many circRNAs in common.
      However, CSSL-4 differentially expressed approximately twice as many circRNAs as
      CSSL-1, and the differential expression levels of the common circRNAs were
      generally higher in CSSL-1 than in CSSL-4. Moreover, two C-RRI comparisons, C-RRI
      vs-C-RRM and C-RRI-vs-C-RSI, possessed a large proportion (approximately 50%) of
      the commonly and differentially expressed circRNAs. These results indicate that
      the differentially expressed circRNAs may play roles in the Verticillium wilt
      response in cotton. A total of 280 differentially expressed circRNAs were
      identified. A Gene Ontology analysis showed that most of the 'stimulus response'
      term source genes were NBS family genes, of which most were the source genes from
      the differentially expressed circRNAs, indicating that NBS genes may play a role
      in Verticillium wilt resistance and might be regulated by circRNAs in the disease
      resistance process in cotton.

PMID- 29576970
TI  - Repetitive low intensity magnetic field stimulation in a neuronal cell line: a
      metabolomics study.
AB  - Low intensity repetitive magnetic stimulation of neural tissue modulates neuronal
      excitability and has promising therapeutic potential in the treatment of
      neurological disorders. However, the underpinning cellular and biochemical
      mechanisms remain poorly understood. This study investigates the behavioural
      effects of low intensity repetitive magnetic stimulation (LI-rMS) at a cellular
      and biochemical level. We delivered LI-rMS (10 mT) at 1 Hz and 10 Hz to B50 rat
      neuroblastoma cells in vitro for 10 minutes and measured levels of selected
      metabolites immediately after stimulation. LI-rMS at both frequencies depleted
      selected tricarboxylic acid (TCA) cycle metabolites without affecting the main
      energy supplies. Furthermore, LI-rMS effects were frequency-specific with 1 Hz
      stimulation having stronger effects than 10 Hz. The observed depletion of
      metabolites suggested that higher spontaneous activity may have led to an
      increase in GABA release. Although the absence of organised neural circuits and
      other cellular contributors (e.g., excitatory neurons and glia) in the B50 cell
      line limits the degree to which our results can be extrapolated to the human
      brain, the changes we describe provide novel insights into how LI-rMS modulates
      neural tissue.

PMID- 29576972
TI  - Recalibrating the body: visuotactile ventriloquism aftereffect.
AB  - Visuotactile ventriloquism is a recently reported effect showing that somatotopic
      tactile representations (namely, representation of location along the surface of
      one's arm) can be biased by simultaneous presentation of a visual stimulus in a
      spatial localization task along the surface of the skin. Here we investigated
      whether the exposure to discrepancy between tactile and visual stimuli on the
      skin can induce lasting changes in the somatotopic representations of space. We
      conducted an experiment investigating this question by asking participants to
      perform a localization task that included unisensory and bisensory trials, before
      and after exposure to spatially discrepant visuotactile stimuli. Participants
      localized brief flashes of light and brief vibrations that were presented along
      the surface of their forearms, and were presented either individually (unisensory
      conditions) or were presented simultaneously at the same location or different
      locations. We then compared the localization of tactile stimuli in unisensory
      tactile conditions before and after the exposure to discrepant bisensory stimuli.
      After exposure, participants exhibited a shift in their tactile localizations in
      the direction of the visual stimulus that was presented during the exposure
      block. These results demonstrate that the somatotopic spatial representations are
      capable of rapidly recalibrating after a very brief exposure to visually
      discrepant stimuli.

PMID- 29576971
TI  - Characterization of the basic helix-loop-helix gene family and its tissue
      differential expression in response to salt stress in poplar.
AB  - The basic helix-loop-helix (bHLH) transcription factor gene family is one of the
      largest gene families and extensively involved in plant growth, development, and
      stress responses. However, limited studies are available on the gene family in
      poplar. In this study, we focused on 202 bHLH genes, exploring their DNA and
      protein sequences and physicochemical properties. According to their protein
      sequence similarities, we classified the genes into 25 groups with specific motif
      structures. In order to explore their expressions, we performed gene expression
      profiling using RNA-Seq and identified 19 genes that display tissue-differential
      expression patterns without treatment. Furthermore, we also performed gene
      expression profiling under salt stress. We found 74 differentially expressed
      genes (DEGs), which are responsive to the treatment. A total of 18 of the 19
      genes correspond well to the DEGs. We validated the results using reverse
      transcription quantitative real-time PCR. This study lays the foundation for
      future studies on gene cloning, transgenes, and biological mechanisms.

PMID- 29576973
TI  - Gender disparities in the association between socio-demographics and non
      communicable disease risk factors among adults with disabilities in Shanghai,
      China.
AB  - Background: Non-communicable disease (NCD) risk factors can co-exist with
      disability and cause a greater burden on the health status of adults with
      disabilities. A lack of egalitarian social policies in China may result in gender
      disparities in the NCD risk factors of adults with disabilities. However, little
      is known about the gender disparities in the association between socio
      demographics and NCD risk factors among adults with disabilities in China;
      consequently, we examined this association among adults with disabilities in
      Shanghai, China. Methods: We used the health examination data of 44,896 adults
      with disabilities in Shanghai in 2014. Descriptive analyses and logistic
      regression models were conducted to estimate gender disparities in the
      association between socio-demographics, disability characteristics, and four
      selected NCD risk factors among adults with disabilities-including high blood
      pressure, high blood glucose, high blood lipids, and being overweight. We
      estimated marginal effects (MEs) on NCD risk factors between gender and other
      confounders. Results: Women with disabilities were about 11.6 percentage points
      more likely to suffer from high blood lipids and less likely to develop the other
      three risk factors than men were. The association of age group, residence permit,
      education level, marital status, and disability type with health outcomes varied
      by gender among adults with disabilities. The difference in age effects between
      men and women was more pronounced in older age groups. Urban residence was
      associated with less risk of high blood pressure risk among women (DeltaME =  -
      0.035, p < 0.01), but no significant difference in other NCD risk factors.
      Education remained a major protective factor against high blood pressure, high
      blood glucose and being overweight among women with disabilities (MEs < 0, p <
      0.05); however, this did not hold for men. The difference in marriage effects
      between men and women was observed in high blood lipids (DeltaME =  - 0.048 for
      the married group and -0.054 for the divorced or widowed group) and overweight
      individuals (DeltaME =  - 0.091 for the married group and -0.114 for the divorced
      or widowed group). Women with intellectual disabilities or mental disabilities
      reported worse health conditions than men did. Discussion: Preventive strategies
      and interventions on NCD risk factors for adults with disabilities should take
      into account gender disparities in these socio-demographic effects. Rural women
      or poorly educated women with disabilities can be a vulnerable population that
      requires more health education and promotion strategies. Health education for
      caregivers of women with intellectual or mental disabilities may also play a
      vital role in preventing their NCD risk factors.

PMID- 29576974
TI  - Searching the Internet for psychiatric disorders among Arab and Jewish Israelis:
      insights from a comprehensive infodemiological survey.
AB  - Israel represents a complex and pluralistic society comprising two major ethno
      national groups, Israeli Jews and Israeli Arabs, which differ in terms of
      religious and cultural values as well as social constructs. According to the so
      called "diversification hypothesis", within the framework of e-health and in the
      era of new information and communication technologies, seeking online health
      information could be a channel to increase health literacy, especially among
      disadvantaged groups. However, little is known concerning digital seeking
      behavior and, in particular, digital mental health literacy. This study was
      conducted in order to fill in this gap. Concerning raw figures, unadjusted for
      confounding variables (time, population size, Internet penetration index, disease
      rate), "depression" searched in Hebrew was characterized by 1.5 times higher
      search volumes, slightly declining throughout time, whereas relative search
      volumes (RSVs) related to "depression" searched in Arabic tended to increase over
      the years. Similar patterns could be detected for "phobia" (in Hebrew 1.4-fold
      higher than in Arabic) and for "anxiety" (with the searches performed in Hebrew
      2.3 times higher than in Arabic). "Suicide" in Hebrew was searched 2.0-fold more
      than in Arabic (interestingly for both languages search volumes exhibited
      seasonal cyclic patterns). Eating disorders were searched more in Hebrew: 8.0
      times more for "bulimia", whilst "anorexia" was searched in Hebrew only. When
      adjusting for confounding variables, association between digital seeking behavior
      and ethnicity remained statistically significant (p-value < 0.0001) for all
      psychiatric disorders considered in the current investigation, except for
      "bulimia" (p = 0.989). More in details, Israeli Arabs searched for mental health
      disorders less than Jews, apart from "depression". Arab and Jewish Israelis,
      besides differing in terms of language, religion, social and cultural values,
      have different patterns of usage of healthcare services and provisions, as well
      as e-healthcare services concerning mental health. Policy- and decision-makers
      should be aware of this and make their best efforts to promote digital health
      literacy among the Arab population in Israel.

PMID- 29576977
TI  - Seasonal temperature acclimatization in a semi-fossorial mammal and the role of
      burrows as thermal refuges.
AB  - Small mammals in habitats with strong seasonal variation in the thermal
      environment often exhibit physiological and behavioral adaptations for coping
      with thermal extremes and reducing thermoregulatory costs. Burrows are especially
      important for providing thermal refuge when above-ground temperatures require
      high regulatory costs (e.g., water or energy) or exceed the physiological
      tolerances of an organism. Our objective was to explore the role of burrows as
      thermal refuges for a small endotherm, the pygmy rabbit (Brachylagus idahoensis),
      during the summer and winter by quantifying energetic costs associated with
      resting above and below ground. We used indirect calorimetry to determine the
      relationship between energy expenditure and ambient temperature over a range of
      temperatures that pygmy rabbits experience in their natural habitat. We also
      measured the temperature of above- and below-ground rest sites used by pygmy
      rabbits in eastern Idaho, USA, during summer and winter and estimated the
      seasonal thermoregulatory costs of resting in the two microsites. Although pygmy
      rabbits demonstrated seasonal physiological acclimatization, the burrow was an
      important thermal refuge, especially in winter. Thermoregulatory costs were lower
      inside the burrow than in above-ground rest sites for more than 50% of the winter
      season. In contrast, thermal heterogeneity provided by above-ground rest sites
      during summer reduced the role of burrows as a thermal refuge during all but the
      hottest periods of the afternoon. Our findings contribute to an understanding of
      the ecology of small mammals in seasonal environments and demonstrate the
      importance of burrows as thermal refuge for pygmy rabbits.

PMID- 29576976
TI  - Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus.
AB  - Haemonchus contortus is the most pathogenic nematode of small ruminants.
      Infection in sheep and goats results in anaemia that decreases animal
      productivity and can ultimately cause death. The involvement of ruminant-specific
      galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play
      important roles in protective immune responses against parasitic infection;
      however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14
      ligands in H. contortus were identified from larval (L4) and adult parasitic
      stages extracts using immobilised LGALS-11 and LGALS-14 affinity column
      chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more
      putative protein targets in the adult stage of H. contortus (43 proteins) when
      compared to the larval stage (two proteins). Of the 43 proteins identified in the
      adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14,
      respectively, with 26 proteins binding to both galectins. Interestingly,
      hematophagous stage-specific sperm-coating protein and zinc metalloprotease
      (M13), which are known vaccine candidates, were identified as putative ligands of
      both LGALS-11 and LGALS-14. The identification of glycoproteins of H. contortus
      by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and
      the potential for developing new interventions.

PMID- 29576975
TI  - Half-lives of PAHs and temporal microbiota changes in commonly used urban
      landscaping materials.
AB  - Background: Polycyclic aromatic hydrocarbons (PAHs) accumulate in urban soils,
      and PAH contamination can change soil microbial community composition.
      Environmental microbiota is associated with human commensal microbiota, immune
      system and health. Therefore, studies investigating the degradation of PAHs, and
      the consequences of soil pollution on microbial communities in urban landscaping
      materials, are crucial. Methods: Four landscaping materials (organic matter 1, 2,
      13 and 56%) were contaminated with PAHs commonly found at urban sites
      (phenanthrene, fluoranthene, pyrene, chrysene and benzo(b)fluoranthene) in PAH
      concentrations that reflect urban soils in Finland (2.4 ug g -1 soil dry weight).
      PAHs were analyzed initially and after 2, 4, 8 and 12 weeks by gas chromatography
      mass spectrometry. Half-lives of PAHs were determined based on 12-weeks
      degradation. Bacterial communities were analyzed at 1 and 12 weeks after
      contamination using Illumina MiSeq 16S rRNA gene metabarcoding. Results: Half
      lives ranged from 1.5 to 4.4 weeks for PAHs with relatively low molecular weights
      (phenanthrene, fluoranthene and pyrene) in landscaping materials containing 1-2%
      organic matter. In contrast, in materials containing 13% and 56% organic matter,
      the half-lives ranged from 2.5 to 52 weeks. Shorter half-lives of phenanthrene
      and fluoranthene were thus associated with low organic matter content. The half
      life of pyrene was inversely related to the relative abundance of Beta-, Delta-
      and Gammaproteobacteria, and diversity of Bacteroidetes and Betaprotebacteria.
      Compounds with higher molecular weights followed compound-specific patterns.
      Benzo(b)fluoranthene was resistant to degradation and half-life of chrysene was
      shorter when the relative abundance of Betaproteobacteria was high. Temporal
      microbiota changes involved increase in the relative abundance of
      Deltaproteobacteria and decrease in genera Flavobacterium and Rhodanobacter.
      Exposure to PAHs seems to adjust microbial community composition, particularly
      within class Beta- and Deltaproteobacteria. Conclusions: In this study, PAH
      degradation depended on the organic matter content and bacterial community
      composition of landscaping materials. Contamination seems to alter bacterial
      community composition in landscaping materials depending on material type. This
      alteration includes changes in bacterial phyla associated with human health and
      immune system. This may open new possibilities for managing urban environments by
      careful selection of landscaping materials, to benefit health and wellbeing.

PMID- 29576978
TI  - Escaping and repairing behaviors of the termite Odontotermes formosanus
      (Blattodea: Termitidae) in response to disturbance.
AB  - The escaping behavior of termites has been documented under laboratory
      conditions; however, no study has been conducted in a field setting due to the
      difficulty of observing natural behaviors inside wood or structures (e.g., nests,
      tunnels, etc.). The black-winged termite, Odontotermes formosanus (Shiraki), is a
      subterranean macrotermitine species which builds extensive mud tubes on tree
      trunks. In the present study, 41 videos (totaling ~2,700 min) were taken on 22
      colonies/subcolonies of O. formosanus after their mud tubes were partially
      damaged by hand. In general, termites consistently demonstrated three phases of
      escape, including initiation (wandering near the mud-tube breach), individual
      escaping (single termites moving downward), and massive, unidirectional escaping
      flows (groups of termites moving downward). Downward moving and repairing were
      the dominant behavioral activities of individuals and were significantly more
      frequent than upward moving, turning/backward moving, or wandering.
      Interestingly, termites in escaping flows moved significantly faster than
      escaping individuals. Repairing behavior was observed shortly after the
      disturbance, and new mud tubes were preferentially constructed from the bottom
      up. When predators (i.e., ants) were present, however, termites stopped moving
      and quickly sealed the mud-tube openings by capping the broken ends. Our study
      provides an interesting example that documents an animal (besides humans)
      simultaneously carrying out pathway repairs and emergency evacuation without
      congestion.

PMID- 29576979
TI  - Assessing soil bacterial community and dynamics by integrated high-throughput
      absolute abundance quantification.
AB  - Microbial ecological studies have been remarkably promoted by the high-throughput
      sequencing approach with explosive information of taxonomy and relative
      abundance. However, relative abundance does not reflect the quantity of the
      microbial community and the inter-sample differences among taxa. In this study,
      we refined and applied an integrated high-throughput absolute abundance
      quantification (iHAAQ) method to better characterize soil quantitative bacterial
      community through combining the relative abundance (by high-throughput
      sequencing) and total bacterial quantities (by quantitative PCR). The proposed
      iHAAQ method was validated by an internal reference strain EDL933 and a
      laboratory strain WG5. Application of the iHAAQ method to a soil phenanthrene
      biodegradation study showed that for some bacterial taxa, the changes of relative
      and absolute abundances were coincident, while for others the changes were
      opposite. With the addition of a microbial activity inhibitor (NaN3), the
      absolute abundances of soil bacterial taxa, including several dominant genera of
      Bacillus, Flavobacterium, and Paenibacillus, decreased significantly, but their
      relative abundances increased after 28 days of incubation. We conclude that the
      iHAAQ method can offer more comprehensive information to reflect the dynamics of
      soil bacterial community with both relative and absolute abundances than the
      relative abundance from high-throughput sequencing alone.

PMID- 29576980
TI  - The right thalamus may play an important role in anesthesia-awakening regulation
      in frogs.
AB  - Background: Previous studies have shown that the mammalian thalamus is a key
      structure for anesthesia-induced unconsciousness and anesthesia-awakening
      regulation. However, both the dynamic characteristics and probable lateralization
      of thalamic functioning during anesthesia-awakening regulation are not fully
      understood, and little is known of the evolutionary basis of the role of the
      thalamus in anesthesia-awakening regulation. Methods: An amphibian species, the
      South African clawed frog (Xenopus laevis) was used in the present study. The
      frogs were immersed in triciane methanesulfonate (MS-222) for general anesthesia.
      Electroencephalogram (EEG) signals were recorded continuously from both sides of
      the telencephalon, diencephalon (thalamus) and mesencephalon during the pre
      anesthesia stage, administration stage, recovery stage and post-anesthesia stage.
      EEG data was analyzed including calculation of approximate entropy (ApEn) and
      permutation entropy (PE). Results: Both ApEn and PE values differed significantly
      between anesthesia stages, with the highest values occurring during the awakening
      period and the lowest values during the anesthesia period. There was a
      significant correlation between the stage durations and ApEn or PE values during
      anesthesia-awakening cycle primarily for the right diencephalon (right thalamus).
      ApEn and PE values for females were significantly higher than those for males.
      Discussion: ApEn and PE measurements are suitable for estimating depth of
      anesthesia and complexity of amphibian brain activity. The right thalamus appears
      physiologically positioned to play an important role in anesthesia-awakening
      regulation in frogs indicating an early evolutionary origin of the role of the
      thalamus in arousal and consciousness in land vertebrates. Sex differences exist
      in the neural regulation of general anesthesia in frogs.

PMID- 29576981
TI  - Large-scale assessment of commensalistic-mutualistic associations between African
      birds and herbivorous mammals using internet photos.
AB  - Birds sitting or feeding on live large African herbivorous mammals are a visible,
      yet quite neglected, type of commensalistic-mutualistic association. Here, we
      investigate general patterns in such relationships at large spatial and taxonomic
      scales. To obtain large-scale data, an extensive internet-based search for photos
      was carried out on Google Images. To characterize patterns of the structural
      organization of commensalistic-mutualistic associations between African birds and
      herbivorous mammals, we used a network analysis approach. We then employed
      phylogenetically-informed comparative analysis to explore whether features of
      bird visitation of mammals, i.e., their mean number, mass and species richness
      per mammal species, are shaped by a combination of host mammal (body mass and
      herd size) and environmental (habitat openness) characteristics. We found that
      the association web structure was only weakly nested for commensalistic as well
      as for mutualistic birds (oxpeckers Buphagus spp.) and African mammals. Moreover,
      except for oxpeckers, nestedness did not differ significantly from a null model
      indicating that birds do not prefer mammal species which are visited by a large
      number of bird species. In oxpeckers, however, a nested structure suggests a non
      random assignment of birds to their mammal hosts. We also identified some new or
      rare associations between birds and mammals, but we failed to find several
      previously described associations. Furthermore, we found that mammal body mass
      positively influenced the number and mass of birds observed sitting on them in
      the full set of species (i.e., taking oxpeckers together with other bird
      species). We also found a positive correlation between mammal body mass and mass
      of non-oxpecker species as well as oxpeckers. Mammal herd size was associated
      with a higher mass of birds in the full set of species as well as in non-oxpecker
      species, and mammal species living in larger herds also attracted more bird
      species in the full set of species. Habitat openness influenced the mass of birds
      sitting on mammals as well as the number of species recorded sitting on mammals
      in the full set of species. In non-oxpecker species habitat openness was
      correlated with the bird number, mass and species richness. Our results provide
      evidence that patterns of bird-mammal associations can be linked to mammal and
      environmental characteristics and highlight the potential role of information
      technologies and new media in further studies of ecology and evolution. However,
      further study is needed to get a proper insight into the biological and
      methodological processes underlying the observed patterns.

PMID- 29576982
TI  - The effect of tides on nearshore environmental DNA.
AB  - We can recover genetic information from organisms of all kinds using
      environmental sampling. In recent years, sequencing this environmental DNA (eDNA)
      has become a tractable means of surveying many species using water, air, or soil
      samples. The technique is beginning to become a core tool for ecologists,
      environmental scientists, and biologists of many kinds, but the temporal
      resolution of eDNA sampling is often unclear, limiting the ecological
      interpretations of the resulting datasets. Here, in a temporally and spatially
      replicated field study using ca. 313 bp of eukaryotic COI mtDNA as a marker, we
      find that nearshore organismal communities are largely consistent across tides.
      Our findings suggest that nearshore eDNA from both benthic and planktonic taxa
      tends to be endogenous to the site and water mass sampled, rather than changing
      with each tidal cycle. However, where physiochemical water mass characteristics
      change, we find that the relative contributions of a broad range of organisms to
      eDNA communities shift in concert.

PMID- 29576983
TI  - Fatigue and perceptual responses of heavier- and lighter-load isolated lumbar
      extension resistance exercise in males and females.
AB  - Background: There is a lack of research considering acute fatigue responses to
      high- and low-load resistance training as well as the comparison between male and
      female responses. Furthermore, limited studies have considered fatigue response
      testing with the inclusion of perceptions of discomfort and exertion. Methods:
      The present study included males (n = 9; 23.8 +/- 6.4 years; 176.7 +/- 6.2 cm;
      73.9 +/- 9.3 kg) and females (n = 8; 21.3 +/- 0.9 years; 170.5 +/- 6.1 cm; 65.5
      +/- 10.8 kg) who were assessed for differences in fatigue (i.e., loss of torque
      at maximal voluntary contraction (MVC)) immediately following isolated lumbar
      extension (ILEX) exercise at heavy- (HL) and light-(LL) loads (80% and 50% MVC,
      respectively). Participants also reported perceptual measures of effort (RPE-E)
      and discomfort (RPE-D) between different resistance training protocols. Results:
      Analysis of variance revealed significantly greater absolute and relative fatigue
      following LL compared to HL conditions (p < 0.001). Absolute fatigue
      significantly differed between males and females (p = 0.012), though relative
      fatigue was not significantly different (p = 0.160). However, effect sizes for
      absolute fatigue (HL; Males = -1.84, Females = -0.83; LL; Males = -3.11, Females
      = -2.39) and relative fatigue (HL; Males = -2.17, Females = -0.76; LL; Males = 
      3.36, Females = -3.08) were larger for males in both HL and LL conditions. RPE-E
      was maximal for all participants in both conditions, but RPE-D was significantly
      higher in LL compared to HL (p < 0.001) with no difference between males and
      females. Discussion: Our data suggests that females do not incur the same degree
      of fatigue as males following similar exercise protocols, and indeed that females
      might be able to sustain longer exercise duration at the same relative loads. As
      such females should manipulate training variables accordingly, perhaps performing
      greater repetitions at a relative load, or using heavier relative loads than
      males. Furthermore, since lighter load exercise is often prescribed in
      rehabilitation settings (particularly for the lumbar extensors) it seems prudent
      to know that this might not be necessary to strengthen musculature and indeed
      might be contraindicated to avoid the increased fatigue and discomfort associated
      with LL exercise.

PMID- 29576984
TI  - Stable isotopes of Hawaiian spiders reflect substrate properties along a
      chronosequence.
AB  - The Hawaiian Islands offer a unique opportunity to test how changes in the
      properties of an isolated ecosystem are propagated through the organisms that
      occur within that ecosystem. The age-structured arrangement of volcanic-derived
      substrates follows a regular progression over space and, by inference, time. We
      test how well documented successional changes in soil chemistry and associated
      vegetation are reflected in organisms at higher trophic levels-specifically,
      predatory arthropods (spiders)-across a range of functional groups. We focus on
      three separate spider lineages: one that builds capture webs, one that hunts
      actively, and one that specializes on eating other spiders. We analyze spiders
      from three sites across the Hawaiian chronosequence with substrate ages ranging
      from 200 to 20,000 years. To measure the extent to which chemical signatures of
      terrestrial substrates are propagated through higher trophic levels, we use
      standard stable isotope analyses of nitrogen and carbon, with plant leaves
      included as a baseline. The target taxa show the expected shift in isotope ratios
      of delta15N with trophic level, from plants to cursorial spiders to web-builders
      to spider eaters. Remarkably, organisms at all trophic levels also precisely
      reflect the successional changes in the soil stoichiometry of the island
      chronosequence, demonstrating how the biogeochemistry of the entire food web is
      determined by ecosystem succession of the substrates on which the organisms have
      evolved.

PMID- 29576985
TI  - Influence of allelic variations in relation to norepinephrine and
      mineralocorticoid receptors on psychopathic traits: a pilot study.
AB  - Background: Past findings support a relationship between abnormalities in the
      amygdala and the presence of psychopathic traits. Among other genes and
      biomarkers relevant to the amygdala, norepinephrine and mineralocorticoid
      receptors might both play a role in psychopathy due to their association with
      traits peripheral to psychopathy. The purpose is to examine if allelic variations
      in single nucleotide polymorphisms related to norepinephrine and
      mineralocorticoid receptors play a role in the display of psychopathic traits and
      executive functions. Methods: Fifty-seven healthy participants from the community
      provided a saliva sample for SNP sampling of rs5522 and rs5569. Participants then
      completed the Psychopathic Personality Inventory-Short Form (PPI-SF) and the
      Tower of Hanoi. Results: Allelic variations of both rs5522 and rs5569 were
      significant when compared to PPI-SF total score and the fearless dominance
      component of the PPI-SF. A significant result was also obtained between rs5522
      and the number of moves needed to complete the 5-disk Tower of Hanoi. Conclusion:
      This pilot study offers preliminary results regarding the effect of allelic
      variations in SNPs related to norepinephrine and mineralocorticoid receptors on
      the presence of psychopathic traits. Suggestions are provided to enhance the
      reliability and validity of a larger-scale study.

PMID- 29576986
TI  - The systematic position of the enigmatic thyreophoran dinosaur Paranthodon
      africanus, and the use of basal exemplifiers in phylogenetic analysis.
AB  - The first African dinosaur to be discovered, Paranthodon africanus was found in
      1845 in the Lower Cretaceous of South Africa. Taxonomically assigned to numerous
      groups since discovery, in 1981 it was described as a stegosaur, a group of
      armoured ornithischian dinosaurs characterised by bizarre plates and spines
      extending from the neck to the tail. This assignment has been subsequently
      accepted. The type material consists of a premaxilla, maxilla, a nasal, and a
      vertebra, and contains no synapomorphies of Stegosauria. Several features of the
      maxilla and dentition are reminiscent of Ankylosauria, the sister-taxon to
      Stegosauria, and the premaxilla appears superficially similar to that of some
      ornithopods. The vertebral material has never been described, and since the last
      description of the specimen, there have been numerous discoveries of thyreophoran
      material potentially pertinent to establishing the taxonomic assignment of the
      specimen. An investigation of the taxonomic and systematic position of
      Paranthodon is therefore warranted. This study provides a detailed re
      description, including the first description of the vertebra. Numerous
      phylogenetic analyses demonstrate that the systematic position of Paranthodon is
      highly labile and subject to change depending on which exemplifier for the clade
      Stegosauria is used. The results indicate that the use of a basal exemplifier may
      not result in the correct phylogenetic position of a taxon being recovered if the
      taxon displays character states more derived than those of the basal exemplifier,
      and we recommend the use, minimally, of one basal and one derived exemplifier per
      clade. Paranthodon is most robustly recovered as a stegosaur in our analyses,
      meaning it is one of the youngest and southernmost stegosaurs.

PMID- 29576987
TI  - Conserving relics from ancient underground worlds: assessing the influence of
      cave and landscape features on obligate iron cave dwellers from the Eastern
      Amazon.
AB  - The degradation of subterranean habitats is believed to represent a serious
      threat for the conservation of obligate subterranean dwellers (troglobites), many
      of which are short-range endemics. However, while the factors influencing cave
      biodiversity remain largely unknown, the influence of the surrounding landscape
      and patterns of subterranean connectivity of terrestrial troglobitic communities
      have never been systematically assessed. Using spatial statistics to analyze the
      most comprehensive speleological database yet available for tropical caves, we
      first assess the influence of iron cave characteristics and the surrounding
      landscape on troglobitic communities from the Eastern Amazon. We then determine
      the spatial pattern of troglobitic community composition, species richness,
      phylogenetic diversity, and the occurrence of frequent troglobitic species, and
      finally quantify how different landscape features influence the connectivity
      between caves. Our results reveal the key importance of habitat amount, guano,
      water, lithology, geomorphology, and elevation in shaping iron cave troglobitic
      communities. While mining within 250 m from the caves influenced species
      composition, increasing agricultural land cover within 50 m from the caves
      reduced species richness and phylogenetic diversity. Troglobitic species
      composition, species richness, phylogenetic diversity, and the occurrence of
      frequent troglobites showed spatial autocorrelation for up to 40 km. Finally, our
      results suggest that the conservation of cave clusters should be prioritized, as
      geographic distance was the main factor determining connectivity between
      troglobitic communities. Overall, our work sheds important light onto one of the
      most overlooked terrestrial ecosystems, and highlights the need to shift
      conservation efforts from individual caves to subterranean habitats as a whole.

PMID- 29576989
TI  - The contribution of Earth observation technologies to the reporting obligations
      of the Habitats Directive and Natura 2000 network in a protected wetland.
AB  - Background: Wetlands are highly productive systems that supply a host of
      ecosystem services and benefits. Nonetheless, wetlands have been drained and
      filled to provide sites for building houses and roads and for establishing
      farmland, with an estimated worldwide loss of 64-71% of wetland systems since
      1900. In Europe, the Natura 2000 network is the cornerstone of current
      conservation strategies. Every six years, Member States must report on
      implementation of the European Habitats Directive. The present study aims to
      illustrate how Earth observation (EO) technologies can contribute to the
      reporting obligations of the Habitats Directive and Natura 2000 network in
      relation to wetland ecosystems. Methods: We analysed the habitat changes that
      occurred in a protected wetland (in NW Spain), 13 years after its designation as
      Natura 2000 site (i.e., between 2003 and 2016). For this purpose, we analysed
      optical multispectral bands and water-related and vegetation indices derived from
      data acquired by Landsat 7 TM, ETM+ and Landsat 8 OLI sensors. To quantify the
      uncertainty arising from the algorithm used in the classification procedure and
      its impact on the change analysis, we compared the habitat change estimates
      obtained using 10 different classification algorithms and two ensemble
      classification approaches (majority and weighted vote). Results: The habitat maps
      derived from the ensemble approaches showed an overall accuracy of 94% for the
      2003 data (Kappa index of 0.93) and of 95% for the 2016 data (Kappa index of
      0.94). The change analysis revealed important temporal dynamics between 2003 and
      2016 for the habitat classes identified in the study area. However, these changes
      depended on the classification algorithm used. The habitat maps obtained from the
      two ensemble classification approaches showed a reduction in habitat classes
      dominated by salt marshes and meadows (24.6-26.5%), natural and semi-natural
      grasslands (25.9-26.5%) or sand dunes (20.7-20.9%) and an increase in forest (31
      34%) and reed bed (60.7-67.2%) in the study area. Discussion: This study
      illustrates how EO-based approaches might be particularly useful to help (1)
      managers to reach decisions in relation to conservation, (2) Member States to
      comply with the requirements of the European Habitats Directive (92/43/EEC), and
      (3) the European Commission to monitor the conservation status of the natural
      habitat types of community interest listed in Annex I of the Directive.
      Nonetheless, the uncertainty arising from the large variety of classification
      methods used may prevent local managers from basing their decisions on EO data.
      Our results shed light on how different classification algorithms may provide
      very different quantitative estimates, especially for water-dependent habitats.
      Our findings confirm the need to account for this uncertainty by applying
      ensemble classification approaches, which improve the accuracy and stability of
      remote sensing image classification.

PMID- 29576988
TI  - Tea saponin reduces the damage of Ectropis obliqua to tea crops, and exerts
      reduced effects on the spiders Ebrechtella tricuspidata and Evarcha albaria
      compared to chemical insecticides.
AB  - Background: Tea is one of the most economically important crops in China.
      However, the tea geometrid (Ectropis obliqua), a serious leaf-feeding pest,
      causes significant damage to tea crops and reduces tea yield and quality. Spiders
      are the most dominant predatory enemies in the tea plantation ecosystem, which
      makes them potentially useful biological control agents of E. obliqua. These
      highlight the need for alternative pest control measures. Our previous studies
      have shown that tea saponin (TS) exerts insecticidal activity against
      lepidopteran pests. Here, we investigate whether TS represents a potentially new
      alternative insecticide with no harm to spiders. Methods: We investigated
      laboratory bioactivities and the field control properties of TS solution against
      E. obliqua. (i) A leaf-dip bioassay was used to evaluate the toxicity of TS to
      3rd-instar E. obliqua larvae and effects of TS on the activities of enzymes
      glutathione-S-transferase (GST), acetylcholinesterase (AChE), carboxylesterase
      (CES) and peroxidase (POD) of 3rd-instar E. obliqua larvae in the laboratory.
      (ii) Topical application was used to measure the toxicity of 30% TS (w/v) and two
      chemical insecticides (10% bifenthrin EC and 50% diafenthiuron SC) to two species
      of spider, Ebrechtella tricuspidata and Evarcha albaria. (iii) Field trials were
      used to investigate the controlling efficacy of 30% TS against E. obliqua larvae
      and to classify the effect of TS to spiders in the tea plantation. Results: The
      toxicity of TS to 3rd-instar E. obliqua larvae occurred in a dose-dependent
      manner and the LC50 was 164.32 mg/mL. Activities of the detoxifying-related
      enzymes, GST and POD, increased in 3rd-instar E. obliqua larvae, whereas AChE and
      CES were inhibited with time by treatment with TS. Mortalities of E. tricuspidata
      and E. albaria after 48 h with 30% TS treatment (16.67% and 20%, respectively)
      were significantly lower than those with 10% bifenthrin EC (80% and 73.33%,
      respectively) and 50% diafenthiuron EC (43.33% and 36.67%, respectively). The
      highest controlling efficacy of 30% TS was 77.02% at 5 d after treatment, which
      showed no difference to 10% bifenthrin EC or 50% diafenthiuron SC. 30% TS was
      placed in the class N (harmless or slightly harmful) of IOBC (International
      Organization of Biological Control) categories for natural enemies, namely
      spiders. Conclusions: Our results indicate that TS is a botanical insecticide
      that has a good controlling efficacy in E. obliqua larvae, which suggests it has
      promise as application in the integrated pest management (IPM) envisaged for tea
      crops.

PMID- 29576990
TI  - Necessity of electrically conductive pili for methanogenesis with magnetite
      stimulation.
AB  - Background: Magnetite-mediated direct interspecies electron transfer (DIET)
      between Geobacter and Methanosarcina species is increasingly being invoked to
      explain magnetite stimulation of methane production in anaerobic soils and
      sediments. Although magnetite-mediated DIET has been documented in defined co
      cultures reducing fumarate or nitrate as the electron acceptor, the effects of
      magnetite have only been inferred in methanogenic systems. Methods:
      Concentrations of methane and organic acid were analysed with a gas chromatograph
      and high-performance liquid chromatography, respectively. The concentration of
      HCl-extractable Fe(II) was determined by the ferrozine method. The association of
      the defined co-cultures of G. metallireducens and M. barkeri with magnetite was
      observed with transmission electron micrographs. Results: Magnetite stimulated
      ethanol metabolism and methane production in defined co-cultures of G.
      metallireducens and M. barkeri; however, magnetite did not promote methane
      production in co-cultures initiated with a culture of G. metallireducens that
      could not produce electrically conductive pili (e-pili), unlike the conductive
      carbon materials that facilitate DIET in the absence of e-pili. Transmission
      electron microscopy revealed that G. metallireducens and M. barkeri were closely
      associated when magnetite was present, as previously observed in G.
      metallireducens/G. sulfurreducens co-cultures. These results show that magnetite
      can promote DIET between Geobacter and Methanosarcina species, but not as a
      substitute for e-pili, and probably functions to facilitate electron transfer
      from the e-pili to Methanosarcina. Conclusion: In summary, the e-pili are
      necessary for the stimulation of not only G. metallireducens/G. sulfurreducens,
      but also methanogenic G. metallireducens/M. barkeri co-cultures with magnetite.

PMID- 29576991
TI  - Cenozoic aridization in Central Eurasia shaped diversification of toad-headed
      agamas (Phrynocephalus; Agamidae, Reptilia).
AB  - We hypothesize the phylogenetic relationships of the agamid genus Phrynocephalus
      to assess how past environmental changes shaped the evolutionary and
      biogeographic history of these lizards and especially the impact of
      paleogeography and climatic factors. Phrynocephalus is one of the most diverse
      and taxonomically confusing lizard genera. As a key element of Palearctic
      deserts, it serves as a promising model for studies of historical biogeography
      and formation of arid habitats in Eurasia. We used 51 samples representing 33 of
      40 recognized species of Phrynocephalus covering all major areas of the genus.
      Molecular data included four mtDNA (COI, ND2, ND4, Cytb; 2,703 bp) and four nuDNA
      protein-coding genes (RAG1, BDNF, AKAP9, NKTR; 4,188 bp). AU-tests were
      implemented to test for significant differences between mtDNA- and nuDNA-based
      topologies. A time-calibrated phylogeny was estimated using a Bayesian relaxed
      molecular clock with nine fossil calibrations. We reconstructed the ancestral
      area of origin, biogeographic scenarios, body size, and the evolution of habitat
      preference. Phylogenetic analyses of nuDNA genes recovered a well-resolved and
      supported topology. Analyses detected significant discordance with the less
      supported mtDNA genealogy. The position of Phrynocephalus mystaceus conflicted
      greatly between the two datasets. MtDNA introgression due to ancient
      hybridization best explained this result. Monophyletic Phrynocephalus contained
      three main clades: (I) oviparous species from south-western and Middle Asia; (II)
      viviparous species of Qinghai-Tibetan Plateau (QTP); and (III) oviparous species
      of the Caspian Basin, Middle and Central Asia. Phrynocephalus originated in late
      Oligocene (26.9 Ma) and modern species diversified during the middle Miocene
      (14.8-13.5 Ma). The reconstruction of ancestral areas indicated that
      Phrynocephalus originated in Middle East-southern Middle Asia. Body size
      miniaturization likely occurred early in the history of Phrynocephalus. The
      common ancestor of Phrynocephalus probably preferred sandy substrates with the
      inclusion of clay or gravel. The time of Agaminae radiation and origin of
      Phrynocephalus in the late Oligocene significantly precedes the landbridge
      between Afro-Arabia and Eurasia in the Early Miocene. Diversification of
      Phrynocephalus coincides well with the mid-Miocene climatic transition when a
      rapid cooling of climate drove progressing aridification and the Paratethys
      salinity crisis. These factors likely triggered the spreading of desert habitats
      in Central Eurasia, which Phrynocephalus occupied. The origin of the viviparous
      Tibetan clade has been associated traditionally with uplifting of the QTP;
      however, further studies are needed to confirm this. Progressing late Miocene
      aridification, the decrease of the Paratethys Basin, orogenesis, and Plio
      Pleistocene climate oscillations likely promoted further diversification within
      Phrynocephalus. We discuss Phrynocephalus taxonomy in scope of the new analyses.

PMID- 29576992
TI  - High resolution crystal structures of the receptor-binding domain of Clostridium
      botulinum neurotoxin serotypes A and FA.
AB  - The binding specificity of botulinum neurotoxins (BoNTs) is primarily a
      consequence of their ability to bind to multiple receptors at the same time.
      BoNTs consist of three distinct domains, a metalloprotease light chain (LC), a
      translocation domain (HN) and a receptor-binding domain (HC). Here we report the
      crystal structure of HC/FA, complementing an existing structure through the
      modelling of a previously unresolved loop which is important for receptor
      binding. Our HC/FA structure also contains a previously unidentified disulphide
      bond, which we have also observed in one of two crystal forms of HC/A1. This may
      have implications for receptor-binding and future recombinant toxin production.

PMID- 29576993
TI  - New Insights about Cloud Vertical Structure from CloudSat and CALIPSO
      observations.
AB  - Active cloud observations from A-Train's CloudSat and CALIPSO satellites offer
      new opportunities to examine the vertical structure of hydrometeor layers. We use
      the 2B-CLDCLASS-LIDAR merged CloudSat-CALIPSO product to examine global aspects
      of hydrometeor vertical stratification. We group the data into major Cloud
      Vertical Structure (CVS) classes based on our interpretation of how clouds in
      three standard atmospheric layers overlap, and provide their global frequency of
      occurrence. The two most frequent CVS classes are single-layer (per our
      definition) low and high clouds which represent ~53% of cloudy skies, followed by
      high clouds overlying low clouds, and vertically extensive clouds that occupy
      near-contiguously a large portion of the troposphere. The prevalence of these
      configurations changes seasonally and geographically, between daytime and
      nighttime, and between continents and oceans. The radiative effects of the CVS
      classes reveal the major radiative warmers and coolers from the perspective of
      the planet as a whole, the surface, and the atmosphere. Single-layer low clouds
      dominate planetary and atmospheric cooling, and thermal infrared surface warming.
      We also investigate the consistency between passive and active views of clouds by
      providing the CVS breakdowns of MODIS cloud regimes for spatiotemporally
      coincident MODIS-Aqua (also on the A-Train) and CloudSat-CALIPSO daytime
      observations. When the analysis is expanded for a more in-depth look at the most
      heterogeneous of the MODIS cloud regimes, it ultimately confirms previous
      interpretations of their makeup that did not have the benefit of collocated
      active observations.

PMID- 29576995
TI  - Surface Connectivity and Interocean Exchanges From Drifter-Based Transition
      Matrices.
AB  - Global surface transport in the ocean can be represented by using the observed
      trajectories of drifters to calculate probability distribution functions. The
      oceanographic applications of the Markov Chain approach to modeling include
      tracking of floating debris and water masses, globally and on yearly-to
      centennial time scales. Here we analyze the error inherent with mapping
      trajectories onto a grid and the consequences for ocean transport modeling and
      detection of accumulation structures. A sensitivity analysis of Markov Chain
      parameters is performed in an idealized Stommel gyre and western boundary current
      as well as with observed ocean drifters, complementing previous studies on
      widespread floating debris accumulation. Focusing on two key areas of interocean
      exchange-the Agulhas system and the North Atlantic intergyre transport barrier-we
      assess the capacity of the Markov Chain methodology to detect surface
      connectivity and dynamic transport barriers. Finally, we extend the methodology's
      functionality to separate the geostrophic and nongeostrophic contributions to
      interocean exchange in these key regions.

PMID- 29576994
TI  - Gravity Wave Dynamics in a Mesospheric Inversion Layer: 1. Reflection, Trapping,
      and Instability Dynamics.
AB  - An anelastic numerical model is employed to explore the dynamics of gravity waves
      (GWs) encountering a mesosphere inversion layer (MIL) having a moderate static
      stability enhancement and a layer of weaker static stability above. Instabilities
      occur within the MIL when the GW amplitude approaches that required for GW
      breaking due to compression of the vertical wavelength accompanying the
      increasing static stability. Thus, MILs can cause large-amplitude GWs to yield
      instabilities and turbulence below the altitude where they would otherwise arise.
      Smaller-amplitude GWs encountering a MIL do not lead to instability and
      turbulence but do exhibit partial reflection and transmission, and the
      transmission is a smaller fraction of the incident GW when instabilities and
      turbulence arise within the MIL. Additionally, greater GW transmission occurs for
      weaker MILs and for GWs having larger vertical wavelengths relative to the MIL
      depth and for lower GW intrinsic frequencies. These results imply similar
      dynamics for inversions due to other sources, including the tropopause inversion
      layer, the high stability capping the polar summer mesopause, and lower frequency
      GWs or tides having sufficient amplitudes to yield significant variations in
      stability at large and small vertical scales. MILs also imply much stronger
      reflections and less coherent GW propagation in environments having significant
      fine structure in the stability and velocity fields than in environments that are
      smoothly varying.

PMID- 29576996
TI  - Scaling Properties of Arctic Sea Ice Deformation in a High-Resolution Viscous
      Plastic Sea Ice Model and in Satellite Observations.
AB  - Sea ice models with the traditional viscous-plastic (VP) rheology and very small
      horizontal grid spacing can resolve leads and deformation rates localized along
      Linear Kinematic Features (LKF). In a 1 km pan-Arctic sea ice-ocean simulation,
      the small-scale sea ice deformations are evaluated with a scaling analysis in
      relation to satellite observations of the Envisat Geophysical Processor System
      (EGPS) in the Central Arctic. A new coupled scaling analysis for data on Eulerian
      grids is used to determine the spatial and temporal scaling and the coupling
      between temporal and spatial scales. The spatial scaling of the modeled sea ice
      deformation implies multifractality. It is also coupled to temporal scales and
      varies realistically by region and season. The agreement of the spatial scaling
      with satellite observations challenges previous results with VP models at coarser
      resolution, which did not reproduce the observed scaling. The temporal scaling
      analysis shows that the VP model, as configured in this 1 km simulation, does not
      fully resolve the intermittency of sea ice deformation that is observed in
      satellite data.

PMID- 29576997
TI  - 5-Point programme for sustainable plant protection.
AB  - This position paper intends to stimulate a profound rethinking of contemporary
      agricultural practice. We criticise the current intensity of chemical plant
      protection in Germany as ecologically unsustainable and thus threatening the
      achievement of key targets of environmental protection and nature conservation
      policies. In the first part of the paper, we provide background information on
      the use of plant protection products (PPP) in German agriculture, the role of
      agricultural policy, European pesticide legislation, the principles of and
      framework for environmental risk assessment and risk management of PPP, as well
      as environmental effects of PPP. The second part is presented against the
      backdrop of the European "Sustainable Use Directive" (2009/128/EC). This
      directive requires that "Member States shall adopt National Action Plans to set
      up their quantitative objectives, targets, measures, and timetables to reduce
      risks and impacts of pesticide use on human health and the environment and to
      encourage the development and introduction of integrated pest management and of
      alternative approaches or techniques to reduce dependency on the use of
      pesticides." Reflecting on the corresponding debate in Germany, we suggest the
      following five key principles for a sustainable use of PPP and provide
      recommendations for their implementation: (1) minimising use; (2) identifying,
      quantifying, and communicating risks; (3) optimising risk management; (4)
      compensating for unavoidable effects; (5) internalising external costs.

PMID- 29576998
TI  - Integral approach of sorption coupled with biodegradation for treatment of azo
      dye using Pseudomonas sp.: batch, toxicity, and artificial neural network.
AB  - The present study investigated the removal of azo dye (crystal violet) by
      adsorption (using a low-cost adsorbent fly ash), biodegradation (using bacterial
      species, Pseudomonas sp.), and an integrated approach of sorption coupled with
      biodegradation (using fly ash immobilized with Pseudomonas sp.) on a comparative
      scale. To ascertain immobilization of bacteria on fly ash, immobilized bacterial
      cells were characterized by energy-dispersive X-ray spectroscopy, scanning
      electron microscopy, Fourier-transform-infrared spectroscopy, and fluorescence
      microscopy. Batch studies were conducted for optimization of the process
      parameters for ensuring maximum dye removal. The optimum pH, temperature, and
      initial dye concentration for the highest percentage of dye removal were found to
      be pH 7, 37  degrees C, and 50 mg/L in all the three cases. Under optimized
      conditions, the highest percentage of dye removal was found to be 89.24, 79.64,
      and 99.04% for biodegradation, sorption, and integrated approach of sorption and
      biodegradation, respectively. Finally, phytotoxicity studies carried out with the
      treated water on Cicer arietinum seeds also carried proved that these processes
      and the adsorbent did not exert any toxic effects on the seeds. Artificial neural
      network modeling revealed a close interaction between theoretically predicted and
      experimentally obtained results and with an error of around 1.1%. Thus, this
      novel, environmentally sustainable and economically viable technique may be
      applied for effective removal of crystal violet from industrial wastewater.

PMID- 29576999
TI  - The effect of chitosan-PMAA-NPK nanofertilizer on Pisum sativum plants.
AB  - The use of chitosan (CS) as a carrier for slow fertilizer release is a novel
      trend. The potential effect of this system in agriculture is still debatable.
      Here, chitosan (CS) nanoparticles were obtained by polymerizing methacrylic acid
      (PMAA) for the entrapment of nitrogen, phosphorous and potassium (NPK)
      nanoparticles (NP), each at a time to form CS-PMAA-NPK NPs complex. The impact of
      this complex was evaluated using garden pea (Pisum sativum var. Master B) plants.
      Five-day-old pea seedlings were treated through their root system with CS-PMAA
      NPK NPs at concentrations of 1, 0.5, 0.25, 0.125 and 0.0625 of the stock solution
      (R) for 1, 2, 4 and 7 days. In general, CS-PMAA-NPK NP complex reduced root
      elongation rate and resulted in the accumulation of starch at the root tip in a
      dose-dependent manner within the treated plants. Interestingly, the lowest
      concentrations of 0.0625 and 0.125 R had induced mitotic cell division (MI =
      22.45 +/- 2.68 and 19.72 +/- 3.48, respectively) compared with the control (MI =
      9.09 +/- 3.28). In addition, some of major proteins such as convicilin, vicilin
      and legumin beta were upregulated in plants treated with these low concentrations
      too. However, all concentrations used exhibited genotoxic effect on DNA based on
      the comet assay data after 48 h of treatment. Thus, it is highly recommended to
      consider the negative effects of this carrier system on plants and environment
      that may arise due to its accumulation in the agricultural fields.

PMID- 29577000
TI  - Studies on growth dynamics of embryogenic cell suspension cultures of
      commercially important Indica rice cultivars ASD16 and Pusa basmati.
AB  - Significant efforts are being directed towards the improvement of rice using
      genetic manipulations. A good and reproducible system for recovering fertile
      Indica rice plants is imperative. The aim of this study was to study the
      influence of initial cell density on growth dynamics of suspension cultures. The
      cultures were initiated from 3-week-old embryogenic calli derived from mature
      seeds of Indica rice cultivars ASD16 and Pusa basmati. Growth kinetics of the
      rice cell suspensions were measured and the obtained data reveal that viable
      cells at 3% PCV using 20 ml liquid (N6D) medium and sub-culturing at 7-day
      intervals resulted in rapid increase in fresh and dry weights and the embryogenic
      competency of the cells were found to be high. The growth kinetics analysis
      revealed that ASD16 showed better efficiency for high frequency and viable
      somatic embryo formation as compared to Pusa basmati. The technique was found to
      be suitable for developing somatic embryos for both cultivars ASD16 and Pusa
      basmati, which can be used for many important applications including
      micropropagation and secondary metabolites production.

PMID- 29577001
TI  - Mediastinal Epidermoid Cyst in a 5-Year-Old Girl.
AB  - A 5-year-old girl was referred to our unit with an incidental finding of a lesion
      on the right hemithorax situated within the right atrial shadow. Computed
      tomography thorax showed a well-defined soft tissue lesion felt to be consistent
      with a bronchogenic cyst. The lesion was located in the posterior mediastinum,
      adherent to the diaphragm and inferior vena cava, but did not extend within the
      wall of the esophagus. It was entirely excised via video-assisted thoracoscopy
      converted to open thoracotomy. Histopathology confirmed an encapsulated nodular
      tissue measuring 2.5 * 2.5 * 2 cm lined by squamous type epithelium. Chronic
      inflammatory cells and foreign body giant cell reaction were found in the cyst
      wall. The appearances were that of a benign epidermoid cyst.

PMID- 29577002
TI  - Use of Nonabsorbable Spiral Tacks for Mesh Reinforcement in Thoracoscopic Repair
      of Congenital Diaphragmatic Hernia.
AB  - Thoracoscopic prosthetic repair of congenital diaphragmatic hernia (CDH) is a
      well-established and safe technique in experienced hands but the patching
      procedure is technically demanding and time consuming. To address the challenges
      associated with this process (confined working space and restricted time), the
      aim of this article is to assess the potential improvements in feasibility,
      efficacy, and safety of patch fixation by using nonabsorbable helicoidal tacks in
      neonates and infants for the repair of large CDH by thoracoscopy. The new
      technique has all the advantages of minimal invasive surgery in very young
      children combined with the advantages of reduced operating time and increased
      simplicity, and may be a good option in cases of recurrence.

PMID- 29577003
TI  - Emergency Repair of a Perforated Mycotic Aneurysm with a Self-made Pericardial
      Tube-graft.
AB  - A 63-year-old female with a history of kidney transplantation was admitted for
      emergency repair of a perforated mycotic aneurysm of the right subclavian artery
      (RSA) in combination with a paravertebral and posterior mediastinal abscess.
      After resection of the aneurysm and after radical local debridement, orthotopic
      repair was performed with a self-made pericardial tube graft from the
      brachiocephalic bifurcation to the thoracic outlet. The paravertebral and
      posterior mediastinal abscess was drained. The postoperative course was
      uneventful. Using a self-made readily available pericardial neo-tube enlarges the
      armamentarium of handling complex infective surgical scenarios and presents a
      smart alternative to alloplastic vascular reconstruction.

PMID- 29577004
TI  - Staged Surgical Palliation for HLHS in a Girl with Severe Factor X Deficiency.
AB  - Background  Factor X deficiency (also known as Stuart-Prower factor deficiency)
      is an autosomal recessive extremely rare hereditary hematologic disorder,
      affecting around 1:1,000,000 of the general population. Case Presentation  This
      case report describes a patient with hypoplastic left heart syndrome and severe
      factor X deficiency, who underwent staged surgical palliation. From stage 1
      Norwood palliation, through superior cavopulmonary anastomosis and ending with
      total cavopulmonary connection with satisfactory hemostasis and no significant
      perioperative bleeding complication. Conclusion  The need to maintain hemostasis
      while aiming to prevent intracardiac thrombosis requires multidisciplinary team
      approach including hematologist, cardiac surgeon, pediatric cardiac intensivist,
      and anesthesiologist along with meticulous hemostasis during surgery and careful
      monitoring of coagulation profile in the postoperative period.

PMID- 29577005
TI  - Transposition of Great Arteries with Left Main Coronary Artery Atresia-Case
      Report.
AB  - Background  The coronary artery anatomy in patients with transposition of the
      great artery (TGA) is a contributing factor for outcome in arterial switch
      procedure. Case Presentation  A full-term, 7-day-old baby boy diagnosed as dextro
      TGA (dTGA) with intact ventricular septum. Intraoperatively, the left coronary
      sinus had a blind indentation from which a firm cord-like left main coronary
      artery originates. Procedure completed as usual for a routine arterial switch
      operation. Conclusion  About 5% of patients with D-TGA have a single coronary
      artery. Assessment of blood flow to all branches intraoperatively is mandatory to
      choose between either transfer of single ostium or bypass grafting to the other
      coronary system.

PMID- 29577006
TI  - Immittance Data Validation using Fast Fourier Transformation (FFT) Computation -
      Synthetic and Experimental Examples.
AB  - Exact data of an electric circuit (EC) model of RLC (resistor, inductor,
      capacitor) elements representing rational immittance of LTI (linear, time
      invariant) systems are numerically Fourier transformed to demonstrate within
      error bounds applicability of the Hilbert integral tranform (HT) and Kramers
      Kronig (KK) integral tranform (KKT) method. Immittance spectroscopy (IS) data are
      validated for their HT (KKT) compliance using non-equispaced fast Fourier
      transformation (NFFT) computations. Failing of HT (KKT) testing may not only stem
      from non-compliance with causality, stability and linearity which are readily
      distinguished using anti HT (KKT) relations. It could also indicate violation of
      uniform boundedness to be overcome either by using singly or multiply subtracted
      KK transform (SSKK or MSKK) or by seeking KKT of the same set of data at a
      complementary immit- tance level. Experimental IS data of a fuel cell (FC) are
      also numerically HT (KKT) validated by NFFT assessing whether LTI principles are
      met. Figures of merit are suggested to measure success in numerical validation of
      IS data.

PMID- 29577007
TI  - Immittance Data Validation by Kramers-Kronig Relations - Derivation and
      Implications.
AB  - Explicitly based on causality, linearity (superposition) and stability (time
      invariance) and implicit on continuity (consistency), finiteness (convergence)
      and uniqueness (single valuedness) in the time domain, Kramers-Kronig (KK)
      integral transform (KKT) relations for immittances are derived as pure
      mathematical constructs in the complex frequency domain using the two-sided
      (bilateral) Laplace integral transform (LT) reduced to the Fourier domain for
      sufficiently rapid exponential decaying, bounded immittances. Novel anti KK
      relations are also derived to distinguish LTI (linear, time invariant) systems
      from non-linear, unstable and acausal systems. All relations can be used to test
      KK transformability on the LTI principles of linearity, stability and causality
      of measured and model data by Fourier transform (FT) in immittance spectroscopy
      (IS). Also, integral transform relations are provided to estimate (conjugate)
      immittances at zero and infinite frequency particularly useful to normalise data
      and compare data. Also, important implications for IS are presented and
      suggestions for consistent data analysis are made which generally apply likewise
      to complex valued quantities in many fields of engineering and natural sciences.

PMID- 29577008
TI  - Improved Performance of Ionic Liquid Supercapacitors by using Tetracyanoborate
      Anions.
AB  - Supercapacitors are energy storage devices designed to operate at higher power
      densities than conventional batteries, but their energy density is still too low
      for many applications. Efforts are made to design new electrolytes with wider
      electrochemical windows than aqueous or conventional organic electrolytes in
      order to increase energy density. Ionic liquids (ILs) with wide electrochemical
      stability windows are excellent candidates to be employed as supercapacitor
      electrolytes. ILs containing tetracyanoborate anions [B(CN)4] offer wider
      electrochemical stability than conventional electrolytes and maintain a high
      ionic conductivity (6.9 mS cm-1). Herein, we report the use of ILs containing the
      [B(CN)4] anion for such an application. They presented a high maximum operating
      voltage of 3.7 V, and two-electrode devices demonstrate high specific
      capacitances even when operating at relatively high rates (ca. 20 F g-1 @ 15 A g
      1). This supercapacitor stored more energy and operated at a higher power at all
      rates studied when compared with cells using a commonly studied ILs.

PMID- 29577009
TI  - Intrusive Memories of Trauma in the Laboratory: Methodological Developments and
      Future Directions.
AB  - Purpose of the Review: Intrusive memories are those that spring to mind unbidden,
      e.g. sensory recollections of stressful/traumatic events. We review recent
      methods to monitor intrusions of a stressor (a trauma film) within the
      laboratory. Recent Findings: Recent studies suggest three main methodologies
      after viewing a trauma film by which to monitor intrusions in the laboratory:
      during post-film rest periods, after exposure to trigger cues, and while
      performing an ongoing task. These approaches allow factors to be tested (e.g.
      psychological or pharmacological) that may influence the frequency of occurrence
      of intrusions. Summary: We raise methodological considerations to guide trauma
      film studies using intrusion monitoring in the laboratory to complement
      monitoring approaches in daily life (e.g. diaries). Intrusion monitoring in the
      laboratory also confers greater experimental control and may open novel research
      avenues, to advance intervention development to mitigate problematic intrusive
      memory symptoms.

PMID- 29577010
TI  - Developmental Aspects of Schizotypy and Suspiciousness: a Review.
AB  - Purpose of the Review: This review identifies the early developmental processes
      that contribute to schizotypy and suspiciousness in adolescence and adulthood. It
      includes the most recent literature on these phenomena in childhood. Recent
      Findings: The early developmental processes that affect schizotypy and paranoia
      in later life are complex. In contrast to existing studies of psychiatric
      patients and clinical/nonclinical adult populations, the study of schizotypy and
      suspiciousness in young children and adolescents is possible due to new child
      appropriate dimensional assessments. New assessments and the advancement of
      technology (e.g., virtual reality in mental health) as well as statistical
      modeling (e.g., mediation and latent-class analyses) in large data have helped
      identified the developmental aspects (e.g., psychosocial, neurocognitive and
      brain factors, nutrition, and childhood correlates) that predict schizotypy and
      suspiciousness in later life. Summary: Prospective longitudinal designs in
      community youths can enhance our understanding of the etiology of schizophrenia
      spectrum disorders and, in the future, the development of preventive
      interventions by extending adult theories and interventions to younger
      populations.

PMID- 29577011
TI  - Current Understanding of the Neural Mechanisms of Dissociation in Borderline
      Personality Disorder.
AB  - Purpose of Review: In this article, we aim to give an overview over recent
      neuroimaging research on dissociation in borderline personality disorder (BPD).
      Stress-related dissociation is highly prevalent in BPD, while so far only little
      is known about its neural underpinnings. Recent Findings: Based on research in
      depersonalization and the dissociative subtype of posttraumatic stress disorder,
      it has been proposed that dissociation involves alterations in a cortico-limbic
      network. In BPD, neuroimaging research explicitly focusing on dissociation is
      still scarce. Summary: Functional neuroimaging studies have provided preliminary
      evidence for an altered recruitment and interplay of fronto-limbic regions
      (amygdala, anterior cingulate, inferior frontal gyrus, medial and dorsolateral
      prefrontal cortices) and temporoparietal areas (superior temporal gyrus, inferior
      parietal lobule, fusiform gyrus), which may underlie disrupted affective
      cognitive processing during dissociation in BPD. More neuroimaging research with
      larger samples, clinical control groups, and repeated measurements is needed to
      deepen the understanding of dissociation in BPD.

PMID- 29577012
TI  - Strongyloides stercoralis and relatives: recent advances in general and molecular
      biology.
AB  - Human strongyloidiasis is a threat to global health, presenting significant
      challenges in diagnosis and clinical management. The imperative to incorporate
      strongyoidiasis more fully into control programs for soil-transmitted helminths
      is increasingly recognized. The unique life cycles of S. stercoralis and
      congeneric species contain both free-living and parasitic generations, and
      transcriptomic methods have recently identified genes of potential importance to
      parasitism in these parasites. Proteomics recently revealed stage-specific
      secreted proteins that appear crucial to the host-parasite interaction. A
      comprehensive genome sequencing project for Strongyloides spp. is now nearing
      completion. Recent technical advances in transgenesis for S. stercoralis and S.
      ratti, including the first establishment of stable transgenic lines, promise to
      advance functional evaluations of genes expressed in conjunction with crucial
      life cycle events. Studies employing these methods recently bolstered the
      hypothesis that S. stercoralis uses cellular signaling pathways homologous to
      three that regulate dauer larval development in Caenorhabditis elegans to
      regulate morphogenesis and development of its infective third-stage larva. The
      free-living generation of Strongyloides makes classical genetics formally
      possible. Recent advances, such as a genetic map of S. ratti and a molecular
      genetic and karyotypic analysis of sex determination in S. papillosus, will
      greatly facilitate this approach. Advanced methods for study of chemosensation in
      C. elegans were recently applied to discover numerous host attractant molecules
      that mediate host finding and contact by infective third-stage larvae of
      Strongyloides spp. Finally, nucleic acid-based diagnostic methods have recently
      come to the fore as alternatives to parasitological and immunodiagnostic
      techniques.

PMID- 29577013
TI  - Effect of ribbon width on electrical transport properties of graphene
      nanoribbons.
AB  - There has been growing interest in developing nanoelectronic devices based on
      graphene because of its superior electrical properties. In particular, patterning
      graphene into a nanoribbon can open a bandgap that can be tuned by changing the
      ribbon width, imparting semiconducting properties. In this study, we report the
      effect of ribbon width on electrical transport properties of graphene nanoribbons
      (GNRs). Monolayer graphene sheets and Si nanowires (NWs) were prepared by
      chemical vapor deposition and a combination of nanosphere lithography and metal
      assisted electroless etching from a Si wafer, respectively. Back-gated GNR field
      effect transistors were fabricated on a heavily p-doped Si substrate coated with
      a 300 nm-thick SiO2 layer, by O2 reactive ion etching of graphene sheets using
      etch masks based on Si NWs aligned on the graphene between the two electrodes by
      a dielectrophoresis method. This resulted in GNRs with various widths in a highly
      controllable manner, where the on/off current ratio was inversely proportional to
      ribbon width. The field-effect mobility decreased with decreasing GNR widths due
      to carrier scattering at the GNR edges. These results demonstrate the formation
      of a bandgap in GNRs due to enhanced carrier confinement in the transverse
      direction and edge effects when the GNR width is reduced.

PMID- 29577014
TI  - The impact of violence, perceived stigma, and other work-related stressors on
      depressive symptoms among women engaged in sex work.
AB  - While the physical health risks of sex work have been well documented, fewer
      studies have explored mental health risks associated with sex work. This study
      examined rates of depressive symptoms and associated risk factors among women
      engaged in sex work in Mongolia (n=222), a country experiencing significant
      economic and social development and where mental health infrastructure is in its
      infancy. A linear regression analysis indicated that significant risk factors for
      depressive symptoms included paying partner sexual violence, perceived
      occupational stigma, less social support, and higher harmful alcohol use. As one
      of the first studies to examine depression among sex workers, this study holds
      important social welfare implications for this marginalized population in
      Mongolia and other low-resource settings globally.

PMID- 29577015
TI  - Multifunctional PEGylated Albumin/IR780/Iron Oxide Nanocomplexes for Cancer
      Photothermal Therapy and MR Imaging.
AB  - A multifunctional albumin/superparamagnetic iron oxide nanoparticle (SPIO)
      nanocomplex system to deliver IR780, a photothermal agent, for cancer theranostic
      applications was proposed in this study. Single emulsion method was utilized to
      fabricate the human albumin/IR780/SPIO (HISP) nanocomplexes with a hydrophobic
      core (SPIO and IR780) and a hydrophilic shell (human serum albumin (HSA) and poly
      (ethylene glycol) (PEG)). Effects of PEGylation on the size and surface potential
      of nanocomplexes were analyzed. Nanospheres containing uniformly dispersed SPIO
      was observed using Transmission Electron Microscopy (TEM) imaging. As a potential
      magnetic resonance (MR) imaging agent, the HISP displayed dose-dependent T2
      weighted imaging contrast (R2 = 81.6 mM-1s-1). Good colloidal stability was
      verified from the nanocomplexes under difference circumstances. The nanocomplexes
      were taken up by cancer cells efficiently and led to significant photothermal
      mediated cancer cell death upon short-term near infrared (NIR) irradiation in
      vitro. Via intravenous injection, PEG-HISP can efficiently deliver IR780 to tumor
      sites and showed strong photothermal effect compared to free drug on the mice
      model. Significant tumor suppression by the photothermal treatments using PEG
      HISP was demonstrated from the mice CT26 xenograft model. Good safety profile of
      the PEG-HISP was confirmed from histological examination and liver functional
      analysis. Taken together, the results suggest that PEG-HISP is a safe and robust
      nano-theranostic platform for advanced anti-cancer treatment.

PMID- 29577016
TI  - Iodinated Echogenic Glycol Chitosan Nanoparticles for X-ray CT/US Dual Imaging of
      Tumor.
AB  - Development of biopolymer-based imaging agents which can access rapidly and
      provide detailed information about the diseases has received much attention as an
      alternative to conventional imaging agents. However, development of biopolymer
      based nanomaterials for tumor imaging still remains challenging due to their low
      sensitivity and image resolution. To surmount of these limitations, multimodal
      imaging agents have been developed, and they were widely utilized for theranostic
      applications. Herein, iodine containing echogenic glycol chitosan nanoparticles
      are developed for x-ray computed tomography (CT) and ultrasound (US) imaging of
      tumor diagnosis. X-ray CT/US dual-modal imaging probe was prepared by following
      below two steps. First, iodine-contained diatrizoic acid (DTA) was chemically
      conjugated to the glycol chitosan (GC) for the CT imaging. DTA conjugated GC (GC
      DTA NPs) formed stable nanoparticles with an average diameter of 315 nm. Second,
      perfluoropentane (PFP), a US imaging agent, was physically encapsulated into GC
      DTA NPs by O/W emulsion method yielding GC-DTA-PFP nanoparticles (GC-DTA-PFP
      NPs). The GC-DTA-PFP NPs formed nanoparticles in physiological condition, and
      they presented the strong x-ray CT, and US signals in phantom test in vitro.
      Importantly, GC-DTA-PFP NPs were effectively accumulated on the tumor site by
      enhanced permeation and retention (EPR) effects. Moreover, GC-DTA-PFP NPs showed
      x-ray CT, and US signals in tumor tissues after intratumoral and intravenous
      injection, respectively. Therefore, GC-DTA-PFP NPs indicated that x-ray CT/US
      dual-modal imaging using iodinated echogenic nanoparticles could be provided more
      comprehensive and accurate diagnostic information to diagnosis of tumor.

PMID- 29577017
TI  - High-density human mesenchymal stem cell rings with spatiotemporally-controlled
      morphogen presentation as building blocks for engineering bone diaphyseal tissue.
AB  - Emerging biomimetic tissue engineering strategies aim to partially recapitulate
      fundamental events that transpire during embryonic skeletal development; namely,
      cellular self-organization and targeted morphogenetic pathway activation. Here,
      we describe self-assembled, scaffold-free human mesenchymal stem cell (hMSC)
      rings featuring microparticle-mediated presentation of transforming growth factor
      beta1 (TGF-beta1) and bone morphogenetic protein-2 (BMP-2). We tested the
      hypothesis that spatiotemporally-controlled dual presentation of TGF-beta1 and
      BMP-2 is superior in modulating in vitro endochondral ossification of high
      density cellular constructs compared to single morphogen delivery. hMSC rings
      were engineered by seeding cells with microparticles presenting (1) TGF-beta1,
      (2) BMP-2, or (3) TGF-beta1 + BMP-2 in custom agarose wells to facilitate self
      assembly within 2 d, followed by horizontal culture on glass tubes for 5 weeks.
      At day 2, hMSC rings across groups revealed homogenous cellular organization
      mimetic of early mesenchymal condensation with no evidence of new matrix or
      mineral deposition. Significant early chondrogenic and osteogenic priming
      occurred with TGF-beta1 + BMP-2 presentation compared to single morphogen-loaded
      groups. By week 5, TGF-beta1-loaded hMSC rings had undergone chondrogenesis,
      while presentation of BMP-2 alone or in conjunction with TGF-beta1 stimulated
      chondrogenesis, chondrocyte hypertrophy, and osteogenesis indicative of
      endochondral ossification. Importantly, tissue mineralization was most compelling
      with TGF-beta1 + BMP-2 loading. Lastly, hMSC ring 'building blocks' were shown to
      efficiently fuse into tubes within 6 d post self-assembly. The resulting tubular
      tissue units exhibited structural integrity, highlighting the translational
      potential of this advanced biomimetic technology for potential early implantation
      in long bone defects.

PMID- 29577018
TI  - Ternary Aligned Nanofibers of RGD Peptide-Displaying M13
      Bacteriophage/PLGA/Graphene Oxide for Facilitated Myogenesis.
AB  - Recently, there have been tremendous efforts to develop the biofunctional
      scaffolds by incorporating various biochemical factors. In the present study, we
      fabricated poly(lactic-co-glycolic acid) (PLGA) nanofiber sheets decorated with
      graphene oxide (GO) and RGD peptide. The decoration of GO and RGD peptide was
      readily achieved by using RGD peptide-displaying M13 bacteriophage (RGD-M13
      phage) and electrospinning. Furthermore, the aligned GO-decorated PLGA/RGD
      peptide (GO-PLGA/RGD) ternary nanofiber sheets were prepared by magnetic field
      assisted electrospinning, and their potentials as bifunctional scaffolds for
      facilitating myogenesis were explored. We characterized the physicochemical and
      mechanical properties of the sheets by scanning electron microscopy, Raman
      spectroscopy, contact angle measurement, and tensile test. In addition, the C2C12
      skeletal myoblasts were cultured on the aligned GO-PLGA/RGD nanofiber sheets, and
      their cellular behaviors, including initial attachment, proliferation and
      myogenic differentiation, were evaluated. Our results revealed that the GO
      PLGA/RGD nanofiber sheets had suitable physicochemical and mechanical properties
      for supporting cell growth, and could significantly promote the spontaneous
      myogenic differentiation of C2C12 skeletal myoblasts. Moreover, it was revealed
      that the myogenic differentiation was further accelerated on the aligned GO
      PLGA/RGD nanofiber sheets due to the synergistic effects of RGD peptide, GO and
      aligned nanofiber structure. Therefore, , it is suggested that the aligned GO
      PLGA/RGD ternary nanofiber sheets are one of the most promising approaches for
      facilitating myogenesis and promoting skeletal tissue regeneration.

PMID- 29577019
TI  - Fabrication of Positively Charged Fluorescent Polymer Nanoparticles for Cell
      Imaging and Gene Delivery.
AB  - Development of efficient non-viral gene delivery vector has aroused great
      attention in the past few decades. In this study, we reported a new gene delivery
      vector, positively charged fluorescent conjugated polymer nanoparticles (CPNPs),
      for efficient gene transfection and in-situ intracellular fluorescence imaging.
      The microscopic and spectroscopic characterizations demonstrated that these CPNPs
      possess decent fluorescence performance (e.g. with fluorescence quantum yield of
      70.7+/-0.3%) and small size dimension of ~3.6+/-0.3 nm (DLS result). Fast and
      efficient cellular translocation capability was observed according to the time
      dependent living cell imaging experiments. Nearly all of the cells were loaded
      with CPNPs after co-incubation for 2 h regardless of the cell type. In comparison
      with the commonly used gene delivery vector, lipofectamine 2000 (with gene
      transfection efficiency of 55+/-5% for pEGFP), the gene expression efficiency
      with the positively charged CPNPs (70+/-3% for pEGFP) was improved significantly.
      Intracellular fluorescence imaging results demonstrated that the CPNPs could
      actively assemble close to the periphery of nuclei. Disassembly was not observed
      even 36 h later, which greatly facilitates releasing of pDNA close to the
      periphery of nuclei and thus promotes the gene transfection efficiency.

PMID- 29577020
TI  - Functionalised Carbon Nanotubes Enhance Brain Delivery of Amyloid-Targeting
      Pittsburgh Compound B (PiB)-Derived Ligands.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterised by brain
      accumulation of toxic protein aggregates, including extracellular amyloid beta
      (Abeta) plaques, inflammation, neuronal death and progressive cognitive
      dysfunction. Current diagnostic modalities, based on cognitive tests, fail to
      detect early AD onset, thus emphasising the need to develop improved methods for
      pre-symptomatic disease detection. Building on the properties of the Pittsburgh
      Compound B (PiB), an Abeta-binding molecule suitable to use as positron emission
      tomography (PET) imaging agent, and aiming at using a more clinically available
      modality (like magnetic ressonance imaging, MRI), PiB derivatives have been
      conjugated to the macrocyclic chelator 1,4,7-tris(carboxymethyl)-1,4,7,10
      tetraazacyclododecane (DO3A) monoamide. However, these derivatives do not readily
      cross the highly selective blood-brain barrier (BBB). Taking advantage of the
      capacity of functionalised carbon nanotubes (f-CNTs) to cross biological
      barriers, including the BBB, this manuscript reports on the conjugation of two
      PiB derivative Gd3+ complexes - Gd(L2) and Gd(L3) - to multi-walled f-CNTs (f
      MWNTs) and assessment of their in vivo biodistribution and brain uptake. It is
      shown that Gd(L2) and Gd(L3) can be efficiently loaded onto different f-MWNTs,
      with significant improvement in brain accumulation of the conjugates compared to
      the free metal complexes. Overall, this study demonstrates that f-MWNTs have
      potential to be used as carriers in theranostic applications involving brain
      delivery of BBB impermeable compounds.

PMID- 29577022
TI  - Writing a review article - Are you making these mistakes?
AB  - An explosion of scientific publications over the last decades has increased the
      need for review articles: Carefully crafted scientific review articles can
      provide the novice reader with an overview of a new subject and provide the
      expert with a synthesis of scientific evidence, proof of reproducibility of
      published data and pooled estimates of common truth through meta-analyses.
      Unfortunately, while there are ample presentations and published guidelines for
      the preparation of scientific articles available, detailed information about how
      to properly prepare scientific review articles is relatively scarce. This
      perspective summarizes possible mistakes that can lead to misinformation in
      scientific review articles with the goal to help authors to improve the
      scientific contribution of their review article and thereby, increase the
      respective value of these articles for the scientific community.

PMID- 29577021
TI  - Penicillin Detection by Tobacco Mosaic Virus-Assisted Colorimetric Biosensors.
AB  - The presentation of enzymes on viral scaffolds has beneficial effects such as an
      increased enzyme loading and a prolonged reusability in comparison to
      conventional immobilization platforms. Here, we used modified tobacco mosaic
      virus (TMV) nanorods as enzyme carriers in penicillin G detection for the first
      time. Penicillinase enzymes were conjugated with streptavidin and coupled to TMV
      rods by use of a bifunctional biotin-linker. Penicillinase-decorated TMV
      particles were characterized extensively in halochromic dye-based biosensing.
      Acidometric analyte detection was performed with bromcresol purple as pH
      indicator and spectrophotometry. The TMV-assisted sensors exhibited increased
      enzyme loading and strongly improved reusability, and higher analysis rates
      compared to layouts without viral adapters. They extended the half-life of the
      sensors from 4 - 6 days to 5 weeks and thus allowed an at least 8-fold longer use
      of the sensors. Using a commercial budget-priced penicillinase preparation, a
      detection limit of 100 uM penicillin was obtained. Initial experiments also
      indicate that the system may be transferred to label-free detection layouts.

PMID- 29577023
TI  - Geostatistical estimation and prediction for censored responses.
AB  - Spatially-referenced geostatistical responses that are collected in environmental
      sciences research are often subject to detection limits, where the measures are
      not fully quantifiable. This leads to censoring (left, right, interval, etc), and
      various ad hoc statistical methods (such as choosing arbitrary detection limits,
      or data augmentation) are routinely employed during subsequent statistical
      analysis for inference and prediction. However, inference may be imprecise and
      sensitive to the assumptions and approximations involved in those arbitrary
      choices. To circumvent this, we propose an exact maximum likelihood estimation
      framework of the fixed effects and variance components and related prediction via
      a novel application of the Stochastic Approximation of the Expectation
      Maximization (SAEM) algorithm, allowing for easy and elegant estimation of model
      parameters under censoring. Both simulation studies and application to a real
      dataset on arsenic concentration collected by the Michigan Department of
      Environmental Quality demonstrate the advantages of our method over the available
      naive techniques in terms of finite sample properties of the estimates,
      prediction, and robustness. The proposed methods can be implemented using the R
      package CensSpatial.

PMID- 29577024
TI  - Healthcare-resource utilization associated with radiation to bone across eight
      European countries: Results from a retrospective study.
AB  - Background: Bone metastases and lytic lesions due to multiple myeloma are common
      in advanced cancer and can lead to debilitating complications (skeletal-related
      events [SREs]), including requirement for radiation to bone. Despite the high
      frequency of radiation to bone in patients with metastatic bone disease, our
      knowledge of associated healthcare resource utilization (HRU) is limited.
      Methods: This retrospective study estimated HRU following radiation to bone in
      Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden and
      Switzerland. Eligible patients were >= 20 years old, had bone metastases
      secondary to breast, lung or prostate cancer, or bone lesions associated with
      multiple myeloma, and had received radiation to bone between 1 July 2004 and 1
      July 2009. HRU data were extracted from hospital patient charts from 3.5 months
      before the index SRE (radiation to bone preceded by a SRE-free period of >= 6.5
      months) until 3 months after the last SRE that the patient experienced during the
      study period. Results: In total, 482 patients were included. The number of
      inpatient stays increased from baseline by a mean of 0.52 (standard deviation
      [SD] 1.17) stays per radiation to bone event and the duration of stays increased
      by a mean of 7.8 (SD 14.8) days. Outpatient visits increased by a mean of 4.24
      (SD 6.57) visits and procedures by a mean of 8.51 (SD 7.46) procedures.
      Conclusion: HRU increased following radiation to bone across all countries
      studied. Agents that prevent severe pain and delay the need for radiation have
      the potential to reduce the burden imposed on healthcare resources and patients.

PMID- 29577025
TI  - A simulations approach for meta-analysis of genetic association studies based on
      additive genetic model.
AB  - Meta-analysis of genetic association studies is being increasingly used to assess
      phenotypic differences between genotype groups. When the underlying genetic model
      is assumed to be dominant or recessive, assessing the phenotype differences based
      on summary statistics, reported for individual studies in a meta-analysis, is a
      valid strategy. However, when the genetic model is additive, a similar strategy
      based on summary statistics will lead to biased results. This fact about the
      additive model is one of the things that we establish in this paper, using
      simulations. The main goal of this paper is to present an alternate strategy for
      the additive model based on simulating data for the individual studies. We show
      that the alternate strategy is far superior to the strategy based on summary
      statistics.

PMID- 29577026
TI  - Consensus on Pegylated Interferon Alpha in Treatment of Chronic Hepatitis B.

PMID- 29577027
TI  - Upgrade Combination Response Is Limited by Prolonged Nucelos(t)ide Analogue
      Therapy in HBeAg-positive Chronic Hepatitis B: A Real-life Study.
AB  - Background and Aims: Few previous studies have reported on a combination response
      (hepatitis B virus (HBV) DNA undetected, alanine aminotransferase normalization
      and hepatitis B e antigen (HBeAg) seroconversion) following nucleos(t)ide
      analogue (NAs) long-term therapy in patients with chronic hepatitis B (CHB). This
      study aimed to investigate the combination response on long-term NAs therapy in
      patients with HBeAg-positive CHB and to determine whether prolonged therapy is
      beneficial for combination response, particularly in optimal patients (baseline
      alanine aminotransferase level >=5 upper limit of normal and HBV DNA level <109
      copies/mL). Methods: In total, 280 HBeAg-positive CHB patients were enrolled in
      this study. Among them, 190 were treated with entecavir and 90 were treated with
      telbivudine. Results: The cumulative rates of combination response in the total
      number of patients were 8.6% at 1 year, 13.2% at 2 years, 19.1% at 3 years, 24.2%
      at 4 years and 26.0% at 5 years. In optimal patients, the cumulative rate of
      combination response was significantly higher than that in the non-optimal
      patients at 3 years (p = 0.043); the trend of the cumulative rate was not strong
      at the later time. Interestingly, in optimal patients, combination response
      mainly occurred in the first 3 years. Multivariate analysis identified HBeAg/anti
      HBe seroconversion at 1 year as the only factor for combination response in
      optimal patients (hazard ratio: 16.321; p = 0.000). During the 3 years, the
      proportion with aspartate aminotransaminase to platelet ratio index <=0.5
      increased from 15.6% at baseline to 71.3% at year 3. Conclusions: Upgrading the
      rate of combination response is limited by prolonging the treatment duration of
      NAs from 3 years to 5 years in HBeAg-positive CHB patients; a new switch
      treatment strategy modification should be considered, particularly in optimal
      patients.

PMID- 29577028
TI  - Sustained Responses in Chronic Hepatitis B Patients with Nucleos(t)ide Analogue
      Drug-resistance after Peg-interferon Alfa-2a Add-on Treatment: A Long-term Cohort
      Study.
AB  - Background and Aims: The use of additional nucleos(t)ide analogues (NAs) without
      cross-resistance to previously used NAs as a rescue therapy is recommended by
      most international guidelines for chronic hepatitis B patients with NA
      resistance. We aimed to investigate the efficacy and safety of combination
      therapy of peg-interferon (PegIFN) alfa-2a and NA in these patients, comparing to
      those who switch to an alternative NA therapy without cross-resistance. Methods:
      In this prospective, comparative and cohort study, data were collected from the
      patients' hospital records. Eligible patients were those with hepatitis B e
      antigen (HBeAg) positivity and resistance to one or more NAs. All patients were
      treated with alternative NA alone or in combination with PegIFN alfa-2a for 52
      weeks or 72 weeks, respectively. HBeAg seroconversion was measured at the end of
      follow-up (EOF; more than 104 weeks after the end of treatment). Results: Sixty
      three patients were recruited to the cohort study (NA-therapy group = 31
      patients; combination therapy group of NA and PegIFN alfa-2a = 32 patients). At
      the EOF, significantly more patients in the combination therapy group (13/27,
      48.2%) achieved primary outcome of HBeAg seroconversion than those in the NA
      therapy group (4/32, 12.5%) (p = 0.003). Four patients (14.8%) in the combination
      therapy group achieved hepatitis B surface antigen (HBsAg) loss and HBsAg
      seroconversion, but none in the NA therapy group did (p = 0.039). In the
      combination therapy group, 16 patients (51.6%) achieved HBeAg seroconversion at
      the end of treatment, of which, 11 patients (68.8%) maintained the response until
      EOF. Conclusions: Adding on PegIFN alfa-2a in combination with NA therapy might
      be an appropriate rescue treatment option for patients who have prior NA
      resistance. In addition, combination therapy induced sustained off-treatment
      biochemical responses in these patients.

PMID- 29577030
TI  - EUS-guided Gall Bladder Drainage in Severe Liver Disease: A Single-center
      Experience in Critically Ill Cirrhotics.
AB  - Background and Aims: Acute calculous cholecystitis with impending gall bladder
      perforation in severe liver diseases including decompensated cirrhosis and acute
      on-chronic liver failure (ACLF) is difficult to manage, due to the procedures
      such as cholecystectomy and per cutaneous cholecystostomy being associated with
      high risk and complications in these patients. Methods: Four cases of severe
      liver disease with acute calculous cholecystitis who presented to the Institute
      of Liver and Biliary Sciences (New Delhi, India) for further management were
      included in the study if they underwent endoscopic ultrasound-guided gall bladder
      drainage (EUS-GBD). The patients were followed up for a minimum of 3 months and
      outcomes were recorded. Results: Four cases of severe liver disease (three ACLF
      and one decompensated cirrhosis), with model for end-stage liver disease scores
      of 24, 26, 23 and 25 respectively, presented with acute calculous cholecystitis
      (Tokyo grade III) and systemic sepsis (high total leukocyte counts). Their
      international normalized ratios were 2.3, 2.6, 2.2 and 2.9 respectively, and two
      were in shock, requiring inotropes at presentation. Ultrasonography of the
      abdomen confirmed hugely distended gall bladder with stone impacted at the neck
      and moderate ascites. All these cases underwent EUS-GBD by linear echo endoscope,
      and had the gastric wall punctured in the antrum using a 19G access needle
      followed by dilatation of the tract using controlled radial expansion balloon and
      Sohendra dilator. In three cases, the plastic stents were placed. In the fourth
      case, a Nagi stent was placed. All the patients recovered and were discharged
      within a week. Conclusions: EUS-GBD is challenging in severe liver disease but
      represents a life-saving procedure, and hence can be attempted in such critically
      ill patients with utmost care and precaution.

PMID- 29577029
TI  - HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial
      Response to Nucleos(t)ide Analog: New Switch Study.
AB  - Background and Aims: Hepatitis B surface antigen (HBsAg) loss is seldom achieved
      with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be
      enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We
      assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B
      patients with partial response to a previous NA. Methods: Hepatitis B e antigen
      (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA <200
      IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized
      1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The
      primary endpoint of this study was HBsAg loss at end of treatment. The
      ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96
      weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively,
      who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar
      irrespective of prior NA or baseline HBeAg seroconversion. Among those who
      cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4%
      (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline
      HBsAg <1500 IU/mL and week 24 HBsAg <200 IU/mL were associated with the highest
      rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and
      58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks
      enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusions: Patients
      on long-term NA who are unlikely to meet therapeutic goals can achieve high rates
      of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved
      for some patients by extending treatment from 48 to 96 weeks, although the
      differences in our study cohort were not statistically significant. Baseline and
      on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

PMID- 29577031
TI  - Hepatitis E: Still Waters Run Deep.
AB  - Hepatitis E is an infectious inflammatory disease of the liver caused by the
      hepatitis E virus (HEV), a single-stranded RNA virus. Today, it is estimated that
      there are more than 20 million HEV infections every year, leading to 3.3 million
      symptomatic cases and more than 56,000 deaths. For a long time it was believed
      that HEV was a travel-associated disease, endemic in developing countries with
      poor hygienic standards and unsafe water supply. However, over the past years,
      publications have demonstrated that autochthonous HEV infections in
      industrialized countries are far more common than previously thought. Awareness
      for HEV amongst health care practitioners in industrialized countries is still
      limited. This relatively rare disease is of great importance, especially in
      immunocompromised patients where it can cause chronic liver disease. This article
      comprehensively reviews current literature to give an overview on clinically
      important topics. It will focus on epidemiological aspects, acute and chronic HEV
      infection as well as extra-hepatic manifestations, diagnostic approach and
      treatment options. Furthermore, the article is concluded with a brief outlook on
      perspectives and urgent problems to be addressed in the future.

PMID- 29577032
TI  - Autoimmune Hepatitis in the Asia-Pacific Area.
AB  - Autoimmune hepatitis has been considered as a relatively rare immunological liver
      disease, especially in the Asia-Pacific area. Although the diagnosis criteria and
      immunosuppressive treatment regimens have been established, there are still some
      challenges. According to the different presentations, the personalized management
      of patients who suffer from this disease, including those with chronic or acute
      severe onset, the autoantibody-negative phenotype and cirrhosis are necessarily
      descriptive. Each subgroup of patients should receive an individualized therapy.
      Here, we review the recent studies of autoimmune hepatitis, mainly focusing on
      the epidemiology and genetics, personalized diagnostics, individualized treatment
      strategies, special subgroups and outcomes. Most of the research in the
      literature is based on Japanese and Chinese populations.

PMID- 29577034
TI  - Activation of Anti-tumor Immune Response by Ablation of HCC with Nanosecond
      Pulsed Electric Field.
AB  - Locoregional therapy is playing an increasingly important role in the non
      surgical management of hepatocellular carcinoma (HCC). The novel technique of non
      thermal electric ablation by nanosecond pulsed electric field has been recognized
      as a potential locoregional methodology for indicated HCC. This manuscript
      explores the most recent studies to indicate its unique anti-tumor immune
      response. The possible immune mechanism, termed as nano-pulse stimulation, was
      also analyzed.

PMID- 29577033
TI  - Traditional Chinese Medicine and Herb-induced Liver Injury: Comparison with Drug
      induced Liver Injury.
AB  - Cases of suspected herb-induced liver injury (HILI) caused by herbal Traditional
      Chinese Medicines (TCMs) and of drug-induced liver injury (DILI) are commonly
      published in the scientific literature worldwide. As opposed to the multiplicity
      of botanical chemicals in herbal TCM products, which are often mixtures of
      several herbs, conventional Western drugs contain only a single synthetic
      chemical. It is therefore of interest to study how HILI by TCM and DILI compare
      with each other, and to what extent results from each liver injury type can be
      transferred to the other. China is among the few countries with a large
      population using synthetic Western drugs as well as herbal TCM. Therefore, China
      is well suited to studies of liver injury comparing drugs with TCM herbs. Despite
      some concordance, recent analyses of liver injury cases with verified causality,
      using the Roussel Uclaf Causality Assessment Method, revealed major differences
      in HILI caused by TCMs as compared to DILI with respect to the following
      features: HILI cases are less frequently observed as compared to DILI, have a
      smaller proportion of females and less unintentional rechallenge events, and
      present a higher rate of hepatocellular injury features. Since many results were
      obtained among Chinese residents who had access to and had used Western drugs and
      TCM herbs, such ethnic homogeneity supports the contention that the observed
      differences of HILI and DILI in the assessed population are well founded.

PMID- 29577035
TI  - Alcoholic Hepatitis: Lost in Translation.
AB  - Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease.
      The mortality rate associated with alcoholic hepatitis is high, largely due to
      the lack of suitable pharmacological interventions. While there has been
      substantial research in the area, generating pharmacological interventions has
      been plagued by the lack of a robust mouse model both for testing and for
      understanding the underlying pathology. A number of major notable advances have
      been made in this area recently, with the goal of generating a mouse model of
      alcoholic hepatitis. The purpose of this article is to review recent advances in
      modeling alcoholic liver disease both in vitro and in vivo in the mouse, and
      place them in the context of the greater spectrum of alcoholic liver disease,
      with a focus on how we can translate current advances into a high-fidelity model
      of alcoholic hepatitis. In addition, we will review the basic mechanisms of
      alcoholic hepatitis as it is currently understood, focusing on recent
      advancements in diagnosis, prognosis and current pathophysiology, especially as
      it relates to the profound immune dysfunction present during alcoholic hepatitis.

PMID- 29577036
TI  - Update on Liver Failure Following Hepatic Resection: Strategies for Prediction
      and Avoidance of Post-operative Liver Insufficiency.
AB  - Liver resection is increasingly used for a variety of benign and malignant
      conditions. Despite advances in preoperative selection, surgical technique and
      perioperative management, posthepatectomy liver failure (PHLF) is still a leading
      cause of morbidity and mortality following liver resection. Given the devastating
      physiological consequences of PHLF and the lack of effective treatment options,
      identifying risk factors and preventative strategies for PHLF is paramount. In
      the past, a major limitation to conducting high quality research on risk factors
      and prevention strategies for PHLF has been the absence of a standardized
      definition. In this article, we describe relevant definitions for PHLF, discuss
      risk factors and prediction models, and review advances in liver assessment tools
      and PHLF prevention strategies.

PMID- 29577037
TI  - Chylous Ascites: A Review of Pathogenesis, Diagnosis and Treatment.
AB  - Chylous ascites (CA) is a rare form of ascites that results from the leakage of
      lipid-rich lymph into the peritoneal cavity. This usually occurs due to trauma
      and rupture of the lymphatics or increased peritoneal lymphatic pressure
      secondary to obstruction. The underlying etiologies for CA have been classified
      as traumatic, congenital, infectious, neoplastic, postoperative, cirrhotic or
      cardiogenic. Since malignancy and cirrhosis account for about two-thirds of all
      the cases of CA in Western countries, in this article we have attempted to
      reclassify CA based on portal and non-portal etiologies. The diagnosis of CA is
      based on the distinct characteristic of the ascitic fluid which includes a milky
      appearance and a triglyceride level of >200 mg/dL. The management consists of
      identifying and treating the underlying disease process, dietary modification,
      and diuretics. Some studies have also supported the use of agents such as
      orlistat, somatostatin, octreotide and etilefrine. Paracentesis and surgical
      interventions in the form of transjugular intrahepatic portosystemic shunt
      (commonly known as TIPS), peritoneal shunt, angiography with embolization of a
      leaking vessel, and laparotomy remain as treatment options for cases refractory
      to medical management.

PMID- 29577038
TI  - Searching for Bacterial Biofilm in Recurrent Cholangitis in Primary Sclerosing
      Cholangitis: A Case Presentation and Introduction of an Unexplored Disease
      Mechanism.
AB  - Inflammation and fibrosis of the bile ducts are the defining pathological
      characteristics of primary sclerosing cholangitis (PSC). A previously unexplored
      mechanism for recurrent cholangitis, one of PSC's most common presentations, is
      bacterial colonization of the biliary epithelium in the form of biofilm, which
      may confer resistance to antibiotics and host phagocytic machinery. The aim of
      the current study was to assess whether bacteria could be seen on the liver
      explant and whether they organized in the form of biofilm. An explanted PSC liver
      from a 60-year-old male who suffered from recurrent cholangitis was formalin
      fixed, paraffin-embedded and Gram stained. The specimens were observed under
      light microscopy. Neither bacteria nor biofilm were detected. We did not detect
      bacteria or biofilm in the liver explant of a single PSC patient with recurrent
      cholangitis using standard light microscopy. We suspect this may be in part due
      to techniques related to tissue preservation and microscopy.

PMID- 29577039
TI  - Let research leave you breathless, not physical exercise!
AB  - Proper endotyping of EIB and precision medicine strategies would allow subjects
      to fully profit from the very beneficial effects of exercise, without incurring
      health risks or affecting performances http://ow.ly/spjT30irzjX.

PMID- 29577040
TI  - Pseudoneutropenia in lymphangioleiomyomatosis (LAM) patients receiving sirolimus:
      evaluation in a 100 patient cohort.
AB  - In lymphangioleiomyomatosis patients receiving sirolimus treatment, transient
      leukopenia in the morning may be due to circadian rhythm, with leukocyte counts
      recovering later in the day, indicating that a decrease in drug dose may not be
      warranted http://ow.ly/jPFz30iysgV.

PMID- 29577041
TI  - Peripheral alveolar nitric oxide concentration reflects alveolar inflammation in
      autoimmune pulmonary alveolar proteinosis.
AB  - Nitric oxide and alveolar macrophage inflammation http://ow.ly/czCx30i12n8.

PMID- 29577042
TI  - Physicians' perspectives on communication and decision making in clinical
      encounters for treatment of latent tuberculosis infection.
AB  - The aim of the study was to explore the views of tuberculosis (TB) physicians on
      treatment of latent TB infection (LTBI), focusing on decision making and
      communication in clinical practice. 20 Australian TB physicians participated in a
      semistructured interview in person or over the telephone. Interviews were
      recorded, transcribed and analysed thematically. The study identified challenges
      that physicians face when discussing treatment for LTBI with patients. These
      included difficulties explaining the concept of latency (in particular to
      patients from culturally and linguistically diverse backgrounds) and providing
      guidance to patients while still framing treatment decisions as a choice.
      Tailored estimates of the risk of developing TB and the risk of developing an
      adverse effect from LTBI treatment were considered the most important information
      for decision making and discussion with patients. Physicians acknowledged that
      there is a significant amount of unwarranted treatment variation, which they
      attributed to the lack of evidence about the risk-benefit balance of LTBI
      treatment in certain scenarios and guidelines that refer to the need for case-by
      case decision making in many instances. In order to successfully implement LTBI
      treatment at a clinical level, consideration should be given to research on how
      to best address communication challenges arising in clinical encounters.

PMID- 29577043
TI  - Multidimensional fatigue in pulmonary hypertension: prevalence, severity and
      predictors.
AB  - Pulmonary hypertension is a potentially fatal disease. Despite pharmacological
      advances in pulmonary hypertension, fatigue remains common in patients with
      pulmonary hypertension. A convenience sample of 120 participants at an
      international patient conference completed the Multidimensional Fatigue Inventory
      (MFI)-20 scale. Data on New York Heart Association Functional Class, body mass
      index, oxygen use and medication type/use were also collected. There was a high
      prevalence of "severe" to "very severe" fatigue for each dimension: General
      Fatigue (60%), Physical Fatigue (55.8%), Reduced Activity (41.7%), Reduced
      Motivation (32.5%) and Mental Fatigue (27.5%). The mean+/-sd overall MFI-20 score
      was 58+/-5.1. Dimensions with the highest averaged levels were General Fatigue
      (13.40+/-3.61), Physical Fatigue (13.23+/-3.67) and Reduced Activity (11.33+/
      4.16). Body mass index correlated with higher fatigue scores. Phosphodiesterase
      inhibitor plus endothelin receptor antagonist combination negatively predicted
      General Fatigue, Physical Fatigue, Reduced Motivation and Reduced Activity.
      Triple therapy was a significant predictor of General Fatigue, Physical Fatigue
      and Reduced Activity. There were no significant predictors of Mental Fatigue.
      Multidimensional fatigue is common and severe in patients with pulmonary
      hypertension. Phosphodiesterase inhibitor plus endothelin receptor antagonist
      combination resulted in lower scores in most fatigue dimensions. Comprehensive
      assessment of fatigue should be considered in the clinical care of patients with
      pulmonary hypertension and clinical research to develop formal interventions that
      target this disabling symptom.

PMID- 29577044
TI  - Tubulointerstitial Biomarkers for Diabetic Nephropathy.
AB  - Patients with diabetic nephropathy have a higher risk of mortality, mostly from
      cardiovascular complications. Standard biomarkers including serum creatinine,
      estimated glomerular filtration rate, and albuminuria are imprecise, do not
      directly measure renal tissue injury, and are relatively insensitive to small
      changes in renal function. Thus, availability of novel biomarkers that are
      sensitive, specific, and precise as well as able to detect kidney injury and
      predict clinically significant outcomes would be widely useful in diabetic
      nephropathy. Novel biomarkers of the processes that induce tubulointerstitial
      changes may ultimately prove to better predict renal progression and prognosis in
      type 2 diabetes. Recently, certain biomarkers, which were initially identified in
      acute kidney injury, also have been reported to confer value in evaluating
      patients with chronic kidney disease. Biomarkers such as cystatin C, kidney
      injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL),
      angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1)
      reflect tubular injury. In this article, we focused on the potential applications
      of these biomarkers in diabetic nephropathy.

PMID- 29577045
TI  - Pycnogenol(r) Induces Browning of White Adipose Tissue through the PKA Signaling
      Pathway in Apolipoprotein E-Deficient Mice.
AB  - Beige adipocytes in white adipose tissue (WAT) have received considerable
      recognition because of their potential protective effect against obesity.
      Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory
      and antioxidant properties and can improve lipid profiles. However, the effect of
      PYC on obesity has never been explored. In this study, we investigated the
      effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient
      mice. The results showed that PYC treatment clearly reversed body weight and the
      mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but
      no difference in food intake. The morphology results showed that the size of the
      adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed
      mice. Next, we found that PYC upregulated the expression of genes related to
      lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC
      significantly increased the expression of UCP1 and other genes related to beige
      adipogenesis. Additionally, PYC increased the expression of proteins related to
      the protein kinase A (PKA) signaling pathway. The findings suggested that PYC
      decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a
      novel therapeutic target for obesity.

PMID- 29577046
TI  - Beneficial Effects of Human Mesenchymal Stromal Cells on Porcine Hepatocyte
      Viability and Albumin Secretion.
AB  - Porcine hepatocytes transplanted during acute liver failure might support
      metabolic functions until the diseased liver recovers its function. Here, we
      isolated high numbers of viable pig hepatocytes and evaluated hepatocyte
      functionality after encapsulation. We further investigated whether coculture and
      coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells
      (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs (n = 9) were
      harvested, and hepatocytes were isolated from liver suspensions for
      microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted
      alginate hydrogels, either alone or in combination with MSC. Viability, albumin
      secretion, and diazepam catabolism of hepatocytes were measured for one week. 9.2
      +/- 3.6 * 109 hepatocytes with 95.2 +/- 3.1% viability were obtained after
      isolation. At day 3, free hepatocytes displayed 99% viability, whereas
      microencapsulation in alginate and PEG-grafted alginate decreased viability to
      62% and 48%, respectively. Albumin secretion and diazepam catabolism occurred in
      free and microencapsulated hepatocytes. Coencapsulation of hepatocytes with MSC
      significantly improved viability and albumin secretion at days 4 and 8 (p <
      0.05). Coculture with MSC significantly increased and prolonged albumin
      secretion. In conclusion, we established a protocol for isolation and
      microencapsulation of high numbers of viable pig hepatocytes and demonstrated
      that the presence of MSC is beneficial for the viability and function of porcine
      hepatocytes.

PMID- 29577047
TI  - How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases.
AB  - Cardiovascular disease remains the leading cause of death around the globe.
      Cardiac deterioration is associated with irreversible cardiomyocyte loss.
      Understanding how the cardiovascular system develops and the pathological
      processes of cardiac disease will contribute to finding novel and preventive
      therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian
      cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade.
      Continuing research on this pathway has identified other factors like RASSF1A,
      Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP
      pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the
      nucleus and initiate transcriptional activity if the pathway is inhibited. The
      role of Hippo signaling has been widely investigated in organ development and
      cancers. A heart of normal size and function which is critical for survival could
      not be generated without the proper regulation of the Hippo tumor suppressor
      pathway. Recent research has demonstrated a novel role of Hippo signaling in
      cardiovascular disease in the context of development, hypertrophy, angiogenesis,
      regeneration, apoptosis, and autophagy. In this review, we summarize the current
      knowledge of how Hippo signaling modulates pathological processes in
      cardiovascular disease and discuss potential molecular therapeutic targets.

PMID- 29577048
TI  - Leaf-Encapsulated Vaccines: Agroinfiltration and Transient Expression of the
      Antigen Staphylococcal Endotoxin B in Radish Leaves.
AB  - Transgene introgression is a major concern associated with transgenic plant-based
      vaccines. Agroinfiltration can be used to selectively transform nonreproductive
      organs and avoid introgression. Here, we introduce a new vaccine modality in
      which Staphylococcal enterotoxin B (SEB) genes are agroinfiltrated into radishes
      (Raphanw sativus L.), resulting in transient expression and accumulation of SEB
      in planta. This approach can simultaneously express multiple antigens in a single
      leaf. Furthermore, the potential of high-throughput vaccine production was
      demonstrated by simultaneously agroinfiltrating multiple radish leaves using a
      multichannel pipette. The expression of SEB was detectable in two leaf cell types
      (epidermal and guard cells) in agroinfiltrated leaves. ICR mice intranasally
      immunized with homogenized leaves agroinfiltrated with SEB elicited detectable
      antibody to SEB and displayed protection against SEB-induced interferon-gamma
      (IFN-gamma) production. The concept of encapsulating antigens in leaves rather
      than purifying them for immunization may facilitate rapid vaccine production
      during an epidemic disease.

PMID- 29577049
TI  - The Influence of Genetic Variations in the CD86 Gene on the Outcome after
      Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - CD86 molecule is the ligand for both costimulatory (CD28) and coinhibitory (CTLA
      4) molecules, and it regulates immune response after allogeneic hematopoietic
      stem cell transplantation (alloHSCT). Therefore, we postulate that CD86 gene
      variations might influence the outcome after alloHSCT. Altogether, 295 adult
      patients (pts) undergoing related (105 pts) and unrelated (190 pts) donor-matched
      HSCT were genotyped for the following CD86 gene polymorphisms: rs1129055,
      rs9831894, and rs2715267. Moreover, the donors' rs1129055 polymorphism was
      determined. None of the investigated SNPs alone were associated with aGvHD and
      rate of relapse. However, we showed that rs2715267 SNP influenced overall
      survival (OS) after alloHSCT. The 24-month OS for the rs271526GG recipients was
      worse than that for the recipients possessing T allelle (TT or GT genotypes) (p =
      0.009). Moreover, analysis of gene-gene interaction between CD86 and CTLA-4
      showed that having both the A allele for CD86 rs1129055 and the CTLA-4 CT60GG
      genotype in recipients increased the risk of aGvHD about 3.5 times.
      Interestingly, the donors' rs1129055GG genotype and the recipients' CT60GG
      genotype also increased the risk of aGvHD about 2.7-fold. We postulate that
      recipients' CD86 gene polymorphisms influence the overall survival after alloHSCT
      and, together with CTLA-4 polymorphisms, might be considered a risk factor for
      aGvHD.

PMID- 29577050
TI  - Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated
      Review on the Risks Associated with Anticancer Targeted Therapy or
      Immunotherapies.
AB  - Cutaneous adverse drug reactions are commonly seen in patients with anticancer
      drug treatment. Anticancer drugs, including chemotherapy, target therapy, and
      recent immunotherapy causing skin reactions ranging from mild skin rash to life
      threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson
      syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and
      mortality while they are receiving cancer treatments, have been proposed to be a
      result of direct skin toxicity or drug hypersensitivity reactions (these are
      proposed mechanism, not definite). Differentiating SCARs from other more commonly
      seen reactions with a better outcome help prevent discontinuation of therapy and
      inappropriate use of systemic immunosuppressants for presumable allergic
      reactions, of which will affect the clinical outcome. In this article, we have
      reviewed published articles from 1950 to August 2017 for SJS/TEN associated with
      anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We
      aimed to provide an overview of SJS/TEN associated with anticancer drugs to
      increase clinician recognition and accelerate future studies on the
      pathomechanism and managements.

PMID- 29577051
TI  - Aspergillus fumigatus Infection-Induced Neutrophil Recruitment and Location in
      the Conducting Airway of Immunocompetent, Neutropenic, and Immunosuppressed Mice.
AB  - Susceptibility to fungal infection is commonly associated with impaired
      neutrophil responses. To study the mechanisms underlying this association, we
      investigated neutrophil recruitment to the conducting airway wall after
      Aspergillus fumigatus conidium inhalation in mouse models of drug-induced
      immunosuppression and antibody-mediated neutrophil depletion (neutropenia) by
      performing three-dimensional confocal laser-scanning microscopy of whole-mount
      primary bronchus specimens. Actin staining enabled visualization of the
      epithelial and smooth muscle layers that mark the airway wall. Gr-1+ or Ly6G+
      neutrophils located between the epithelium and smooth muscles were considered
      airway wall neutrophils. The number of airway wall neutrophils for
      immunocompetent, immunosuppressed, and neutropenic mice before and 6 h after A.
      fumigatus infection were analyzed and compared. Our results show that the number
      of conducting airway wall neutrophils in immunocompetent mice significantly
      increased upon inflammation, while a dramatic reduction in this number was
      observed following immunosuppression and neutropenia. Interestingly, a slight
      increase in the infiltration of neutrophils into the airway wall was detected as
      a result of infection, even in immunosuppressed and neutropenic mice. Taken
      together, these data indicate that neutrophils are present in intact conducting
      airway walls and the number elevates upon A. fumigatus infection. Conducting
      airway wall neutrophils are affected by both neutropenia and immunosuppression.

PMID- 29577052
TI  - Frequency of Interferon-Resistance Conferring Substitutions in Amino Acid
      Positions 70 and 91 of Core Protein of the Russian HCV 1b Isolates Analyzed in
      the T-Cell Epitopic Context.
AB  - Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can
      affect the response to interferon and are associated with the development of
      hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia
      was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in
      the European (18.0%, p = 0.0010), but lower than that in the US HCV 1b strains
      (62.8%, p < 0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b
      isolates, higher than in Asian isolates (43.8%, p < 0.0001). Thus, a significant
      proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M
      substitution. In silico analysis of the epitopic structure of the regions of
      substitutions revealed that both harbor clusters of T-cell epitopes. Peptides
      encompassing these regions were predicted to bind to a panel of HLA class I
      molecules, with substitutions impairing peptide recognition by HLA I molecules of
      the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M
      substitutions may have evolved as the immune escape variants. Impairment of T
      cell recognition may play a part in the negative effect of these substitutions on
      the response to IFN treatment.

PMID- 29577053
TI  - Hsa_circ_0001859 Regulates ATF2 Expression by Functioning as an MiR-204/211
      Sponge in Human Rheumatoid Arthritis.
AB  - Background: circRNAs are part of the competitive endogenous RNA network, which
      putatively function as miRNA sponges and play a crucial role in the development
      of numerous diseases. However, studies of circRNAs in rheumatoid arthritis (RA)
      disease are limited. This work aims to identify the expression pattern of
      circRNAs in synovial tissues and their inflammatory regulation mechanism.
      Methods: We first compared the mRNA expression in rheumatoid arthritis patients
      with that in healthy volunteers by GEO database mining to identify gene loci
      specifically expressed in synovial tissues. Functional enrichment algorithms were
      then used to draw the interactome diagram of circRNAs-miRNAs-mRNAs. Finally, loss
      of-function and rescue assays of the candidate circRNAs were performed in vitro.
      Results: A total of 29 differentially expressed circRNAs related to rheumatoid
      arthritis were discovered. Silencing of hsa_circ_0001859 suppressed ATF2
      expression and decreased inflammatory activity in SW982 cells. Hsa_circ_0001859
      could compete with ATF2 for miR-204/211. Discussion: These findings indicate that
      hsa_circ_0001859 participates deeply in the process of chronic inflammatory
      disease in synovial tissue.

PMID- 29577055
TI  - Perianal Mucinous Adenocarcinoma Diagnosed by Histological Study of Anorectal
      Abscess with Fistula.
AB  - Perianal mucinous adenocarcinoma (PMA) is an oncologic rarity that poses a
      diagnostic and therapeutic dilemma for treating clinicians because there are few
      reported cases and an absence of definitive guidelines. We report a patient who
      had been treated with local surgery for recurrent perianal abscess with fistula
      for 3 years. Biopsy of the indurated tissue overlying his surgical scars revealed
      PMA. Neoadjuvant concurrent chemoradiotherapy followed by abdominoperineal
      resection was planned to address the locally advanced disease and ongoing sepsis.
      Our case is unique in that the fistula preceded carcinoma by only 3 years instead
      of the typical 10 years.

PMID- 29577054
TI  - Successful Treatment of Bleeding Rectal Varices with Balloon-Occluded Antegrade
      Transvenous Obliteration.
AB  - We report the first described case in the United States of balloon-occluded
      antegrade transvenous obliteration (BATO) performed in a cirrhotic patient with
      recurrent bleeding from large rectal varices. This is a novel interventional
      radiology approach to treat bleeding rectal varices. Our patient was a poor
      candidate for transjugular intrahepatic portosystemic shunt and endoscopic band
      ligation. Successful BATO produced complete resolution of rectal varices and no
      further rectal bleeding. There are no established guidelines for the management
      of rectal varices. We demonstrate that the BATO technique is a viable option to
      treat recurrent bleeding due to rectal varices.

PMID- 29577056
TI  - An Overt, Obscure Gastrointestinal Bleed Caused by a Primary Small Bowel
      Fibroblastic Reticular Cell Sarcoma.
AB  - Small bowel bleeding should be considered in patients who continue to bleed
      despite a negative upper endoscopy and colonoscopy. The differential diagnosis of
      small bowel bleeding can include infection, inflammatory conditions, vascular
      malformations, and, rarely, malignancy. This report demonstrates a rare, primary,
      small bowel, reticular cell sarcoma presenting as an overt gastrointestinal
      bleed. These tumors are difficult to diagnose because they are rarely seen on
      traditional cross-sectional imaging and can present with multiple synchronous
      lesions throughout the intestinal tract.

PMID- 29577057
TI  - Malignant Peritoneal Mesothelioma Presenting as Mucinous Ascites.
AB  - We present a rare case of a 46-year-old man presenting with mucinous ascites
      secondary to malignant peritoneal mesothelioma (MPM) that was diagnosed via
      colonoscopy with biopsies. Both our findings and the clinical presentation were
      unique. While it is widely known that asbestos exposure is commonly associated
      with pleural mesothelioma, 6-10% of malignant mesotheliomas arise from the
      peritoneum. To date, only 4 cases of MPM with the primary tumor site in the colon
      have been described in the literature.

PMID- 29577058
TI  - Infectious Diseases Consultation Reduces 30-Day and 1-Year All-Cause Mortality
      for Multidrug-Resistant Organism Infections.
AB  - Background: Multidrug-resistant organism (MDRO) infections are associated with
      high mortality and readmission rates. Infectious diseases (ID) consultation
      improves clinical outcomes for drug-resistant Staphylococcus aureus bloodstream
      infections. Our goal was to determine the association between ID consultation and
      mortality following various MDRO infections. Methods: This study was conducted
      with a retrospective cohort (January 1, 2006-October 1, 2015) at an academic
      tertiary referral center. We identified patients with MDROs in a sterile site or
      bronchoalveolar lavage/bronchial wash culture. Mortality and readmissions within
      1 year of index culture were identified, and the association of ID consultation
      with these outcomes was determined using Cox proportional hazards models with
      inverse weighting by the propensity score for ID consultation. Results: A total
      of 4214 patients with MDRO infections were identified. ID consultation was
      significantly associated with reductions in 30-day and 1-year mortality for
      resistant S. aureus (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36
      0.63; and HR, 0.73, 95% CI, 0.61-0.86) and Enterobacteriaceae (HR, 0.41; 95% CI,
      0.27-0.64; and HR, 0.74; 95% CI, 0.59-0.94), and 30-day mortality for
      polymicrobial infections (HR, 0.51; 95% CI, 0.31-0.86) but not Acinetobacter or
      Pseudomonas. For resistant Enterococcus, ID consultation was marginally
      associated with decreased 30-day mortality (HR, 0.81; 95% CI, 0.62-1.06). ID
      consultation was associated with reduced 30-day readmission for resistant
      Enterobacteriaceae. Conclusions: ID consultation was associated with significant
      reductions in 30-day and 1-year mortality for resistant S. aureus and
      Enterobacteriaceae, and 30-day mortality for polymicrobial infections. There was
      no association between ID consultation and mortality for patients with resistant
      Pseudomonas, Acinetobacter, or Enterococcus, possibly due to small sample sizes.
      Our results suggest that ID consultation may be beneficial for patients with some
      MDRO infections.

PMID- 29577059
TI  - Degree of Housing Instability Shows Independent "Dose-Response" With Virologic
      Suppression Rates Among People Living With Human Immunodeficiency Virus.
AB  - Housing instability negatively impacts outcomes in people [living] with human
      immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has
      not previously been evaluated. Using 6 dwelling types to measure housing status,
      we found a strong inverse association between housing instability and viral
      suppression across a spectrum of unstable housing arrangements.

PMID- 29577060
TI  - Splenic Infarction: An Under-recognized Complication of Infectious Mononucleosis?
AB  - Splenic infarction is a rare complication of infectious mononucleosis. We
      describe 3 cases of splenic infarction attributed to infectious mononucleosis
      that we encountered within a 2-month period. We underscore the awareness of this
      potential complication of infectious mononucleosis and discuss the differential
      diagnosis of splenic infarction, including infectious etiologies. While
      symptomatic management is usually sufficient for infectious mononucleosis
      associated splenic infarction, close monitoring for other complications,
      including splenic rupture, is mandated.

PMID- 29577061
TI  - Spatial Control of Bacteria Using Screen Printing.
AB  - Synthetic biology has led to advances in both our understanding and engineering
      of genetic circuits that affect spatial and temporal behaviors in living cells. A
      growing array of native and synthetic circuits such as oscillators, pattern
      generators, and cell-cell communication systems has been studied, which exhibit
      spatiotemporal properties. To better understand the design principles of these
      genetic circuits, there is a need for versatile and precise methods for
      patterning cell populations in various configurations. In this study, we develop
      a screen printing methodology to pattern bacteria on agar, glass, and paper
      surfaces. Initially, we tested three biocompatible resuspension media with
      appropriate rheological properties for screen printing. Using microscopy, we
      characterized the resolution and bleed of bacteria screen prints on agar and
      glass surfaces, obtaining resolutions as low as 188 MUm. Next, we engineered
      bacterial strains producing visible chromoproteins analogous to the cyan,
      magenta, and yellow subtractive color system for the creation of multicolored
      bacteria images. Using this system, we printed distinct populations in
      overlapping or interlocking designs on both paper and agar substrates. These
      proof-of-principle experiments demonstrated how the screen printing method could
      be used to study microbial community interactions and pattern formation of
      biofilms at submillimeter length scales. Overall, our approach allows for rapid
      and precise prototyping of patterned bacteria species that will be useful in the
      understanding and engineering of spatiotemporal behaviors in microbial
      communities.

PMID- 29577062
TI  - Conformal Robotic Stereolithography.
AB  - Additive manufacturing by layerwise photopolymerization, commonly called
      stereolithography (SLA), is attractive due to its high resolution and diversity
      of materials chemistry. However, traditional SLA methods are restricted to planar
      substrates and planar layers that are perpendicular to a single-axis build
      direction. Here, we present a robotic system that is capable of maskless
      layerwise photopolymerization on curved surfaces, enabling production of large
      area conformal patterns and the construction of conformal freeform objects. The
      system comprises an industrial six-axis robot and a custom-built maskless
      projector end effector. Use of the system involves creating a mesh representation
      of the freeform substrate, generation of a triangulated toolpath with curved
      layers that represents the target object to be printed, precision mounting of the
      substrate in the robot workspace, and robotic photopatterning of the target
      object by coordinated motion of the robot and substrate. We demonstrate printing
      of conformal photopatterns on spheres of various sizes, and construction of
      miniature three-dimensional objects on spheres without requiring support
      features. Improvement of the motion accuracy and development of freeform
      toolpaths would enable construction of polymer objects that surpass the size and
      support structure constraints imparted by traditional SLA systems.

PMID- 29577063
TI  - Association between Metabolic Syndrome and Recurrence of Nonmuscle Invasive
      Bladder Cancer following bacillus Calmette-Guerin Treatment.
AB  - Introduction: Intravesical bacillus Calmette-Guerin (BCG) therapy is the gold
      standard adjuvant treatment for patients with high-grade non-muscle-invasive
      bladder cancer (NMIBC). Despite the association between metabolic syndrome (MetS)
      and bladder cancer, the association between MetS and BCG failure is unknown. The
      objective of this study was to characterize disease recurrence following BCG in
      patients with and without MetS. Methods: We retrospectively evaluated the records
      of patients undergoing TURBT at our institution in 2012-2015 for NMIBC and
      identified those who received adjuvant BCG therapy. MetS was defined as having
      three of four components: diabetes mellitus, hyperlipidemia, hypertension, or
      body mass index (BMI)>=30kg/m2. The primary outcome was recurrence or
      progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival
      analysis, and Cox multivariable regression analyses were performed. Results: High
      grade was present in 83/90 (92.2%) patients. MetS was present in 27/90 (30%)
      patients. Median follow-up was 20 months. On Kaplan-Meier analysis, patients with
      MetS had worse DFS compared with patient without MetS. On multivariable analysis,
      BMI>=30 kg/m2 was a significant predictor of recurrence or progression (HR 2.94,
      95% CI: 1.43-6.03). Presence of MetS did not significantly affect the type of BCG
      failure. Conclusions: The association between MetS and failure to respond to BCG
      therapy is multifactorial but is in part associated with obesity. Elevated BMI is
      strongly associated with recurrence or progression. Further studies are warranted
      to investigate the relationship between increased adiposity and response to BCG,
      especially as other novel immunotherapeutic agents are likely to enter the NMIBC
      space.

PMID- 29577064
TI  - Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2
      Induced Bone Formation.
AB  - Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration,
      possessing FDA approval for orthopedic applications. BMP2 is often required in
      supratherapeutic doses clinically, yielding adverse side effects and substantial
      treatment costs. Considering the crucial role of materials for BMPs delivery and
      cell osteogenic differentiation, we devote to engineering an innovative bone
      matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our
      previous work describes a novel technique, named thermally induced nanofiber self
      agglomeration (TISA), for generating 3D electrospun nanofibrous (NF)
      polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA,
      leading to increased osteogenic capabilities in vitro, however, these bio-inert
      synthetic polymers produced limited BMP2-induced bone formation in vivo. We
      therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone
      like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a
      favorable osteogenic niche for bone formation at low doses of BMP2. Compared to
      PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced
      osteogenic differentiation capabilities of C2C12 cells with phenamil.
      Importantly, in vivo studies showed this synergism was able to generate
      significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D
      scaffolds act as a favorable synthetic extracellular matrix for bone
      regeneration.

PMID- 29577065
TI  - Docking-based inverse virtual screening: methods, applications, and challenges.
AB  - Identifying potential protein targets for a small-compound ligand query is
      crucial to the process of drug development. However, there are tens of thousands
      of proteins in human alone, and it is almost impossible to scan all the existing
      proteins for a query ligand using current experimental methods. Recently, a
      computational technology called docking-based inverse virtual screening (IVS) has
      attracted much attention. In docking-based IVS, a panel of proteins is screened
      by a molecular docking program to identify potential targets for a query ligand.
      Ever since the first paper describing a docking-based IVS program was published
      about a decade ago, the approach has been gradually improved and utilized for a
      variety of purposes in the field of drug discovery. In this article, the methods
      employed in docking-based IVS are reviewed in detail, including target databases,
      docking engines, and scoring function methodologies. Several web servers
      developed for non-expert users are also reviewed. Then, a number of applications
      are presented according to different research purposes, such as target
      identification, side effects/toxicity, drug repositioning, drug-target network
      development, and receptor design. The review concludes by discussing the
      challenges that docking-based IVS needs to overcome to become a robust tool for
      pharmaceutical engineering.

PMID- 29577066
TI  - AIM interneurons mediate feeding suppression through the TYRA-2 receptor in C.
      elegans.
AB  - Feeding behavior is the most fundamental behavior in C. elegans. Our previous
      results have dissected the central integration circuit for the regulation of
      feeding, which integrates opposing sensory inputs and regulates feeding behavior
      in a nonlinear manner. However, the peripheral integration that acts downstream
      of the central integration circuit to modulate feeding remains largely unknown.
      Here, we find that a Galphai/o-coupled tyramine receptor, TYRA-2, is involved in
      peripheral feeding suppression. TYRA-2 suppresses feeding behavior via the AIM
      interneurons, which receive tyramine/octopamine signals from RIM/RIC neurons in
      the central integration circuit. Our results reveal previously unidentified roles
      for the receptor TYRA-2 and the AIM interneurons in feeding regulation, providing
      a further understanding of how biogenic amines tyramine and octopamine regulate
      feeding behavior.

PMID- 29577067
TI  - PI4KIIalpha regulates insulin secretion and glucose homeostasis via a PKD
      dependent pathway.
AB  - Insulin release by pancreatic beta cells plays a key role in regulating blood
      glucose levels in humans, and to understand the mechanism for insulin secretion
      may reveal therapeutic strategies for diabetes. We found that PI4KIIalpha
      transgenic (TG) mice have abnormal glucose tolerance and higher serum glucose
      levels than wild-type mice. Glucose-stimulated insulin secretion was
      significantly reduced in both PI4KIIalpha TG mice and PI4KIIalpha-overexpressing
      pancreatic beta cell lines. A proximity-based biotin labeling technique, BioID,
      was used to identify proteins that interact with PI4KIIalpha, and the results
      revealed that PI4KIIalpha interacts with PKD and negatively regulates its
      activity. The effect of PI4KIIalpha on insulin secretion was completely rescued
      by altering PKD activity. PI4KIIalpha overexpression also worsened glucose
      tolerance in streptozotocin/high-fat diet-induced diabetic mice by impairing
      insulin secretion. Our study has shed new light on PI4KIIalpha function and
      mechanism in diabetes and identified PI4KIIalpha as an important regulator of
      insulin secretion.

PMID- 29577068
TI  - Identification of small ORF-encoded peptides in mouse serum.
AB  - Identification of the coding elements in the genome is fundamental to interpret
      the development of living systems and species diversity. Small peptides (length <
      100 amino acids) have played an important role in regulating the biological
      metabolism, but their identification has been limited by their size and
      abundance. Serum is the most important body fluid and is full of small peptides.
      In this study, we have established a small ORF-encoded peptides (SEPs) database
      from mouse GENCODE release. This database provides about half a million putative
      translated SEPs in mouse. We also extract serum proteins from wild type and ob/ob
      mice, and collect the low molecular weight proteins for mass spectrometric
      analysis. More than 50 novel SEPs have been discovered. Several SEPs are further
      verified by biochemical method with newly raised antibodies. These novel SEPs
      enhance the knowledge about the complexity of serum and provide new clues for the
      annotation and functional analysis of genes, especially the noncoding elements in
      the genome.

PMID- 29577069
TI  - Identification of natural products as novel ligands for the human 5-HT2C
      receptor.
AB  - G protein-coupled receptors (GPCRs) constitute the largest human protein family
      with over 800 members, which are implicated in many important medical conditions.
      Serotonin receptors belong to the aminergic GPCR subfamily and play important
      roles in physiological and psychological activities. Structural biology studies
      have revealed the structures of many GPCRs in atomic details and provide the
      basis for the identification and investigation of the potential ligands, which
      interact with and modulate the receptors. Here, an integrative approach combining
      a focused target-specific natural compound library, a thermal-shift-based
      screening method, affinity mass spectrometry, molecular docking, and in vitro as
      well as in vivo functional assay, was applied to identify (-)-crebanine and
      several other aporphine alkaloids as initial hits for a human serotonin receptor
      subtype, the 5-HT2C receptor. Further studies illuminated key features of their
      binding affinity, downstream signaling and tissue reaction, providing a molecular
      explanation for the interaction between (-)-crebanine and human 5-HT2C receptor.

PMID- 29577070
TI  - A new two-strip TLC method for the quality control of technetium-99m
      mercaptoacetyl-triglycine (99mTc-MAG3).
AB  - Background: 99mTc-mercaptoacetyl-triglycine (99mTc-MAG3) has been used for
      dynamic renal imaging since about 30 years. Free pertechnetate (99mTcO4),
      colloidal 99mTc ((99mTcO2)n), 99mTc-tartrate (precursor), precomplexes (99mTc
      (MAG3)x) and lipophilic 99mTc-MAG2 are the main radiochemical impurities that may
      occur in the preparation. The total amount of these impurities has to be
      identified before release of the product for patient administration to guarantee
      patient safety and good image quality. The European Pharmacopoeia suggests a
      method based on high-pressure liquid chromatography analysis in combination with
      a paper chromatography. This analytical method is time consuming, expensive and
      requires specially trained technicians. As a consequence, it is not widely
      applied in nuclear medicine radiopharmacies. Results: We developed a simple
      method for radiochemical purity testing of 99mTc-MAG3. The method is based on
      thin layer chromatography with two strips to be developed in parallel. Method
      validation was carried out in comparison to the official methods of the companies
      and to the European Pharmacopoeia method. It was tested on specificity, accuracy,
      robustness and precision. Conclusion: The proposed method is able to identify and
      quantify the sum of all impurities occurring in the preparation, respecting the
      acceptance criteria for the radiochemical purity defined by the official methods.
      Hydrophilic and lipophilic compounds are identified separately and results are
      obtained within less than 20 minutes. Our method is simple, cost effective, fast
      and is suitable for employing dose calibrators or radiometric scanners.

PMID- 29577071
TI  - Temporal fractals in movies and mind.
AB  - Fractal patterns are seemingly everywhere. They can be analyzed through Fourier
      and power analyses, and other methods. Cutting, DeLong, and Nothelfer (2010)
      analyzed as time-series data the fluctuations of shot durations in 150 popular
      movies released over 70 years. They found that these patterns had become
      increasingly fractal-like and concluded that they might be linked to those found
      in the results of psychological tasks involving attention. To explore this
      possibility further, we began by analyzing the shot patterns of almost twice as
      many movies released over a century. The increasing fractal-like nature of shot
      patterns is affirmed, as determined by both a slope measure and a long-range
      dependence measure, neither of which is sensitive to the vector lengths of their
      inputs within the ranges explored here. But the main reason for increased long
      range dependence is related to, but not caused by, the increasing vector length
      of the shot-series samples. It appears that, in generating increasingly fractal
      like patterns, filmmakers have systematically explored dimensions that are
      important for holding our attention-shot durations, scene durations, motion, and
      sound amplitude-and have crafted fluctuations in them like those of our
      endogenous attention patterns. Other dimensions-luminance, clutter, and shot
      scale-are important to film style but their variations seem not to be important
      to holding viewers' moment-to-moment attention and have not changed in their
      fractional dimension over time.

PMID- 29577072
TI  - Theoretical vs. empirical discriminability: the application of ROC methods to
      eyewitness identification.
AB  - Receiver operating characteristic (ROC) analysis was introduced to the field of
      eyewitness identification 5 years ago. Since that time, it has been both
      influential and controversial, and the debate has raised an issue about measuring
      discriminability that is rarely considered. The issue concerns the distinction
      between empirical discriminability (measured by area under the ROC curve) vs.
      underlying/theoretical discriminability (measured by d' or variants of it). Under
      most circumstances, the two measures will agree about a difference between two
      conditions in terms of discriminability. However, it is possible for them to
      disagree, and that fact can lead to confusion about which condition actually
      yields higher discriminability. For example, if the two conditions have
      implications for real-world practice (e.g., a comparison of competing lineup
      formats), should a policymaker rely on the area-under-the-curve measure or the
      theory-based measure? Here, we illustrate the fact that a given empirical ROC
      yields as many underlying discriminability measures as there are theories that
      one is willing to take seriously. No matter which theory is correct, for
      practical purposes, the singular area-under-the-curve measure best identifies the
      diagnostically superior procedure. For that reason, area under the ROC curve
      informs policy in a way that underlying theoretical discriminability never can.
      At the same time, theoretical measures of discriminability are equally important,
      but for a different reason. Without an adequate theoretical understanding of the
      relevant task, the field will be in no position to enhance empirical
      discriminability.

PMID- 29577073
TI  - An assigned responsibility system for robotic teleoperation control.
AB  - This paper proposes an architecture that explores a gap in the spectrum of
      existing strategies for robot control mode switching in adjustable autonomy. In
      situations where the environment is reasonably known and/or predictable, pre
      planning these control changes could relieve robot operators of the additional
      task of deciding when and how to switch. Such a strategy provides a clear
      division of labour between the automation and the human operator(s) before the
      job even begins, allowing for individual responsibilities to be known ahead of
      time, limiting confusion and allowing rest breaks to be planned. Assigned
      Responsibility is a new form of adjustable autonomy-based teleoperation that
      allows the selective inclusion of automated control elements at key stages of a
      robot operation plan's execution. Progression through these stages is controlled
      by automatic goal accomplishment tracking. An implementation is evaluated through
      engineering tests and a usability study, demonstrating the viability of this
      approach and offering insight into its potential applications.

PMID- 29577074
TI  - An enhanced teaching interface for a robot using DMP and GMR.
AB  - This paper develops an enhanced teaching interface tested on both a Baxter robot
      and a KUKA iiwa robot. Movements are collected from a human demonstrator by using
      a Kinect v2 sensor, and then the data is sent to a remote PC for the
      teleoperation with Baxter. Meanwhile, data is saved locally for the playback
      process of the Baxter. The dynamic movement primitive (DMP) is used to model and
      generalize the movements. In order to learn from multiple demonstrations
      accurately, dynamic time warping (DTW), is used to pretreat the data recorded by
      the robot platform and Gaussian mixture model (GMM), aiming to generate multiple
      patterns after the teaching process, are employed for the calculation of the DMP.
      Then the Gaussian mixture regression (GMR) algorithm is applied to generate a
      synthesized trajectory with smaller position errors in 3D space. This proposed
      approach is tested by performing two tasks on a KUKA iiwa and a Baxter robot.

PMID- 29577075
TI  - Understanding Two Different Structures in the Dark Stable State of the Oxygen
      Evolving Complex of Photosystem II: Applicability of the Jahn-Teller Deformation
      Formula.
AB  - Tanaka et al. (J. Am. Chem. Soc., 2017, 139, 1718) recently reported the three
      dimensional (3D) structure of the oxygen evolving complex (OEC) of photosystem II
      (PSII) by X-ray diffraction (XRD) using extremely low X-ray doses of 0.03 and
      0.12 MGy. They observed two different 3D structures of the CaMn4O5 cluster with
      different hydrogen-bonding interactions in the S1 state of OEC keeping the
      surrounding polypeptide frameworks of PSII the same. Our Jahn-Teller (JT)
      deformation formula based on large-scale quantum mechanics/molecular mechanics
      (QM/MM) was applied for these low-dose XRD structures, elucidating important
      roles of JT effects of the MnIII ion for subtle geometric distortions of the
      CaMn4O5 cluster in OEC of PSII. The JT deformation formula revealed the
      similarity between the low-dose XRD and damage-free serial femtosecond X-ray
      diffraction (SFX) structures of the CaMn4O5 cluster in the dark stable state. The
      extremely low-dose XRD structures were not damaged by X-ray irradiation.
      Implications of the present results are discussed in relation to recent SFX
      results and a blue print for the design of artificial photocatalysts for water
      oxidation.

PMID- 29577076
TI  - Neoadjuvant Chemotherapy Considerations in Triple-Negative Breast Cancer.
AB  - The optimal neoadjuvant chemotherapy (NACT) regimen in triple-negative breast
      cancer (TNBC) has not been clearly defined. Achieving a pathologic complete
      response (pCR) provides important prognostic information, and, especially in
      TNBC, is considered a surrogate endpoint for event-free survival. Thus, many
      neoadjuvant studies in TNBC focus on this as a primary endpoint, and such
      information may be used for accelerated US Food and Drug Administration approval.
      Current controversies in the field include: (1) the role of platinum-based
      compounds; (2) the optimal chemotherapy backbone; and (3) the benefits of
      additional therapy after surgery. Conflicting results of 2 major studies adding
      carboplatin to NACT have highlighted the need to balance potential benefits to
      disease outcomes against increased toxicity. While the PROGECT study suggests
      efficacy of a nonanthracycline-containing regimen, this is observational data,
      and evidence in the form of a clinical trial remains to be seen. Data surrounding
      optimal taxane use support the use of nab-paclitaxel in place of paclitaxel in
      limited clinical situations. Although bevacizumab may increase pCR rates, this
      has not translated into survival benefit. Capecitabine shows promise in patients
      who have not achieved pCR after NACT. The neoadjuvant setting remains an
      important model for drug development. This review will focus on the most
      important and most current neoadjuvant trials in women with TNBC.

PMID- 29577077
TI  - ACO2 homozygous missense mutation associated with complicated hereditary spastic
      paraplegia.
AB  - Objective: To identify the clinical characteristics and genetic etiology of a
      family affected with hereditary spastic paraplegia (HSP). Methods: Clinical,
      genetic, and functional analyses involving genome-wide linkage coupled to whole
      exome sequencing in a consanguineous family with complicated HSP. Results: A
      homozygous missense mutation was identified in the ACO2 gene (c.1240T>G
      p.Phe414Val) that segregated with HSP complicated by intellectual disability and
      microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed
      significantly decreased activity of the mitochondrial aconitase enzyme and
      defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an
      essential enzyme in the Krebs cycle. Recessive mutations in this gene have been
      previously associated with cerebellar ataxia. Conclusions: Our findings nominate
      ACO2 as a disease-causing gene for autosomal recessive complicated HSP and
      provide further support for the central role of mitochondrial defects in the
      pathogenesis of HSP.

PMID- 29577078
TI  - Rare ABCA7 variants in 2 German families with Alzheimer disease.
AB  - Objective: The aim of this study was to identify variants associated with
      familial late-onset Alzheimer disease (AD) using whole-genome sequencing.
      Methods: Several families with an autosomal dominant inheritance pattern of AD
      were analyzed by whole-genome sequencing. Variants were prioritized for rare,
      likely pathogenic variants in genes already known to be associated with AD and
      confirmed by Sanger sequencing using standard protocols. Results: We identified 2
      rare ABCA7 variants (rs143718918 and rs538591288) with varying penetrance in 2
      independent German AD families, respectively. The single nucleotide variant (SNV)
      rs143718918 causes a missense mutation, and the deletion rs538591288 causes a
      frameshift mutation of ABCA7. Both variants have previously been reported in
      larger cohorts but with incomplete segregation information. ABCA7 is one of more
      than 20 AD risk loci that have so far been identified by genome-wide association
      studies, and both common and rare variants of ABCA7 have previously been
      described in different populations with higher frequencies in AD cases than in
      controls and varying penetrance. Furthermore, ABCA7 is known to be involved in
      several AD-relevant pathways. Conclusions: We conclude that both SNVs might
      contribute to the development of AD in the examined family members. Together with
      previous findings, our data confirm ABCA7 as one of the most relevant AD risk
      genes.

PMID- 29577079
TI  - Twenty-year-old African American woman with prion disease associated with the
      G114V PRNP variant.

PMID- 29577080
TI  - Mutation in the GCH1 gene with dopa-responsive dystonia and phenotypic
      variability.

PMID- 29577081
TI  - Pharmacogenetic Associations with ADME Variants and Virologic Response to an
      Initial HAART Regimen in HIV-Infected Women.
AB  - Background: Clinical response to highly active antiretroviral therapy (HAART)
      varies among different populations. A portion of this variability may be due to
      variation in genes involved in the absorption, distribution, metabolism, and
      excretion (ADME) of HAART. Design: To identify genetic factors involved in
      virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort
      of HIV-infected women on HAART. A total of 569 HIV-positive participants from the
      Women's Interagency HIV Study who initiated HAART from 1994-2012 and had genotype
      data were included in these analyses. Methods: Admixture maximum likelihood
      burden testing was used to evaluate gene-level associations between common
      genetic variation and virologic response (achieving <80 viral copies/mL) to HAART
      overall and with specific drug classes. Results: Six statistically significant
      (P<0.05) gene-level burden tests were observed with response to specific regimen
      types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to
      protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were
      significantly associated with response to triple nucleoside reverse transcriptase
      inhibitor (NRTI) treatment. Conclusions: Although no genome-wide associations
      with virologic response to HAART overall were detected in this cohort of HIV
      infected women, more statistically significant gene-level burden tests were
      observed than would be expected by chance (two and a half expected, six
      observed). It is likely that variation in one of the significant genes is
      associated with virologic response to certain HAART regimens. Further
      characterization of the genes associated with response to PI-based treatment is
      warranted.

PMID- 29577082
TI  - Talaromyces marneffei simA Encodes a Fungal Cytochrome P450 Essential for
      Survival in Macrophages.
AB  - Fungi are adept at occupying specific environmental niches and often exploit
      numerous secondary metabolites generated by the cytochrome P450 (CYP)
      monoxygenases. This report describes the characterization of a yeast-specific CYP
      encoded by simA ("survival in macrophages"). Deletion of simA does not affect
      yeast growth at 37 degrees C in vitro but is essential for yeast cell production
      during macrophage infection. The DeltasimA strain exhibits reduced conidial
      germination and intracellular growth of yeast in macrophages, suggesting that the
      enzymatic product of SimA is required for normal fungal growth in vivo.
      Intracellular DeltasimA yeast cells exhibit cell wall defects, and metabolomic
      and chemical sensitivity data suggest that SimA may promote chitin synthesis or
      deposition in vitro. In vivo, DeltasimA yeast cells subsequently lyse and are
      degraded, suggesting that SimA may increase resistance to and/or suppress host
      cell biocidal effectors. The results suggest that simA synthesizes a secondary
      metabolite that allows T. marneffei to occupy the specific intracellular
      environmental niche within the macrophage. IMPORTANCE This study in a dimorphic
      fungal pathogen uncovered a role for a yeast-specific cytochrome P450 (CYP)
      encoding gene in the ability of T. marneffei to grow as yeast cells within the
      host macrophages. This report will inspire further research into the role of CYPs
      and secondary metabolite synthesis during fungal pathogenic growth.

PMID- 29577083
TI  - Human Antibody Responses to Emerging Mayaro Virus and Cocirculating Alphavirus
      Infections Examined by Using Structural Proteins from Nine New and Old World
      Lineages.
AB  - Mayaro virus (MAYV), Venezuelan equine encephalitis virus (VEEV), and chikungunya
      virus (CHIKV) are vector-borne alphaviruses that cocirculate in South America.
      Human infections by these viruses are frequently underdiagnosed or misdiagnosed,
      especially in areas with high dengue virus endemicity. Disease may progress to
      debilitating arthralgia (MAYV, CHIKV), encephalitis (VEEV), and death. Few
      standardized serological assays exist for specific human alphavirus infection
      detection, and antigen cross-reactivity can be problematic. Therefore,
      serological platforms that aid in the specific detection of multiple alphavirus
      infections will greatly expand disease surveillance for these emerging
      infections. In this study, serum samples from South American patients with PCR-
      and/or isolation-confirmed infections caused by MAYV, VEEV, and CHIKV were
      examined by using a protein microarray assembled with recombinant capsid,
      envelope protein 1 (E1), and E2 from nine New and Old World alphaviruses.
      Notably, specific antibody recognition of E1 was observed only with MAYV
      infections, whereas E2 was specifically targeted by antibodies from all of the
      alphavirus infections investigated, with evidence of cross-reactivity to E2 of
      o'nyong-nyong virus only in CHIKV-infected patient serum samples. Our findings
      suggest that alphavirus structural protein microarrays can distinguish infections
      caused by MAYV, VEEV, and CHIKV and that this multiplexed serological platform
      could be useful for high-throughput disease surveillance. IMPORTANCE Mayaro,
      chikungunya, and Venezuelan equine encephalitis viruses are closely related
      alphaviruses that are spread by mosquitos, causing diseases that produce similar
      influenza-like symptoms or more severe illnesses. Moreover, alphavirus infection
      symptoms can be similar to those of dengue or Zika disease, leading to
      underreporting of cases and potential misdiagnoses. New methods that can be used
      to detect antibody responses to multiple alphaviruses within the same assay would
      greatly aid disease surveillance efforts. However, possible antibody cross
      reactivity between viruses can reduce the quality of laboratory results. Our
      results demonstrate that antibody responses to multiple alphaviruses can be
      specifically quantified within the same assay by using selected recombinant
      protein antigens and further show that Mayaro virus infections result in unique
      responses to viral envelope proteins.

PMID- 29577084
TI  - Aggregative Adherence and Intestinal Colonization by Enteroaggregative
      Escherichia coli Are Produced by Interactions among Multiple Surface Factors.
AB  - Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers
      that are associated with diarrhea. The genome of EAEC strain 042, a diarrheal
      pathogen validated in a human challenge study, encodes multiple colonization
      factors. Notable among them are aggregative adherence fimbriae (AAF/II) and a
      secreted antiaggregation protein (Aap). Deletion of aap is known to increase
      adherence, autoaggregation, and biofilm formation, so it was proposed that Aap
      counteracts AAF/II-mediated interactions. We hypothesized that Aap sterically
      masks heat-resistant agglutinin 1 (Hra1), an integral outer membrane protein
      recently identified as an accessory colonization factor. We propose that this
      masking accounts for reduced in vivo colonization upon hra1 deletion and yet no
      colonization-associated phenotypes when hra1 is deleted in vitro. Using single
      and double mutants of hra1, aap, and the AAF/II structural protein gene aafA, we
      demonstrated that increased adherence in aap mutants occurs even when AAF/II
      proteins are genetically or chemically removed. Deletion of hra1 together with
      aap abolishes the hyperadherence phenotype, demonstrating that Aap indeed masks
      Hra1. The presence of all three colonization factors, however, is necessary for
      optimal colonization and for rapidly building stacked-brick patterns on slides
      and cultured monolayers, the signature EAEC phenotype. Altogether, our data
      demonstrate that Aap serves to mask nonstructural adhesins such as Hra1 and that
      optimal colonization by EAEC is mediated through interactions among multiple
      surface factors. IMPORTANCE Enteroaggregative Escherichia coli (EAEC) bacteria
      are exceptional colonizers of the human intestine and can cause diarrhea.
      Compared to other E. coli pathogens, little is known about the genes and
      pathogenic mechanisms that differentiate EAEC from harmless commensal E. coli.
      EAEC bacteria attach via multiple proteins and structures, including long
      appendages produced by assembling molecules of AafA and a short surface protein
      called Hra1. EAEC also secretes an antiadherence protein (Aap; also known as
      dispersin) which remains loosely attached to the cell surface. This report shows
      that dispersin covers Hra1 such that the adhesive properties of EAEC seen in the
      laboratory are largely produced by AafA structures. When the bacteria colonize
      worms, dispersin is sloughed off, or otherwise removed, such that Hra1-mediated
      adherence occurs. All three factors are required for optimal colonization, as
      well as to produce the signature EAEC stacked-brick adherence pattern. Interplay
      among multiple colonization factors may be an essential feature of exceptional
      colonizers.

PMID- 29577085
TI  - Evolution of Bacterial Global Modulators: Role of a Novel H-NS Paralogue in the
      Enteroaggregative Escherichia coli Strain 042.
AB  - Bacterial genomes sometimes contain genes that code for homologues of global
      regulators, the function of which is unclear. In members of the family
      Enterobacteriaceae, cells express the global regulator H-NS and its paralogue
      StpA. In Escherichia coli, out of providing a molecular backup for H-NS, the role
      of StpA is poorly characterized. The enteroaggregative E. coli strain 042
      carries, in addition to the hns and stpA genes, a third gene encoding an hns
      paralogue (hns2). We present in this paper information about its biological
      function. Transcriptomic analysis has shown that the H-NS2 protein targets a
      subset of the genes targeted by H-NS. Genes targeted by H-NS2 correspond mainly
      with horizontally transferred (HGT) genes and are also targeted by the Hha
      protein, a fine-tuner of H-NS activity. Compared with H-NS, H-NS2 expression
      levels are lower. In addition, H-NS2 expression exhibits specific features: it is
      sensitive to the growth temperature and to the nature of the culture medium. This
      novel H-NS paralogue is widespread within the Enterobacteriaceae. IMPORTANCE
      Global regulators such as H-NS play key relevant roles enabling bacterial cells
      to adapt to a changing environment. H-NS modulates both core and horizontally
      transferred (HGT) genes, but the mechanism by which H-NS can differentially
      regulate these genes remains to be elucidated. There are several instances of
      bacterial cells carrying genes that encode homologues of the global regulators.
      The question is what the roles of these proteins are. We noticed that the
      enteroaggregative E. coli strain 042 carries a new hitherto uncharacterized copy
      of the hns gene. We decided to investigate why this pathogenic E. coli strain
      requires an extra H-NS paralogue, termed H-NS2. In our work, we show that H-NS2
      displays specific expression and regulatory properties. H-NS2 targets a subset of
      H-NS-specific genes and may help to differentially modulate core and HGT genes by
      the H-NS cellular pool.

PMID- 29577086
TI  - KatharoSeq Enables High-Throughput Microbiome Analysis from Low-Biomass Samples.
AB  - Microbiome analyses of low-biomass samples are challenging because of
      contamination and inefficiencies, leading many investigators to employ low
      throughput methods with minimal controls. We developed a new automated protocol,
      KatharoSeq (from the Greek katharos [clean]), that outperforms single-tube
      extractions while processing at least five times as fast. KatharoSeq incorporates
      positive and negative controls to reveal the whole bacterial community from
      inputs of as few as 50 cells and correctly identifies 90.6% (standard error,
      0.013%) of the reads from 500 cells. To demonstrate the broad utility of
      KatharoSeq, we performed 16S rRNA amplicon and shotgun metagenome analyses of the
      Jet Propulsion Laboratory spacecraft assembly facility (SAF; n = 192, 96), 52
      rooms of a neonatal intensive care unit (NICU; n = 388, 337), and an endangered
      abalone-rearing facility (n = 192, 123), obtaining spatially resolved, unique
      microbiomes reproducible across hundreds of samples. The SAF, our primary focus,
      contains 32 sOTUs (sub-OTUs, defined as exact sequence matches) and their
      inferred variants identified by the deblur algorithm, with four (Acinetobacter
      lwoffii, Paracoccus marcusii, Mycobacterium sp., and Novosphingobium) being
      present in >75% of the samples. According to microbial spatial topography, the
      most abundant cleanroom contaminant, A. lwoffii, is related to human foot traffic
      exposure. In the NICU, we have been able to discriminate environmental exposure
      related to patient infectious disease, and in the abalone facility, we show that
      microbial communities reflect the marine environment rather than human input.
      Consequently, we demonstrate the feasibility and utility of large-scale, low
      biomass metagenomic analyses using the KatharoSeq protocol. IMPORTANCE Various
      indoor, outdoor, and host-associated environments contain small quantities of
      microbial biomass and represent a niche that is often understudied because of
      technical constraints. Many studies that attempt to evaluate these low-biomass
      microbiome samples are riddled with erroneous results that are typically false
      positive signals obtained during the sampling process. We have investigated
      various low-biomass kits and methods to determine the limit of detection of these
      pipelines. Here we present KatharoSeq, a high-throughput protocol combining
      laboratory and bioinformatic methods that can differentiate a true positive
      signal in samples with as few as 50 to 500 cells. We demonstrate the application
      of this method in three unique low-biomass environments, including a SAF, a
      hospital NICU, and an abalone-rearing facility.

PMID- 29577087
TI  - Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters
      Lifetime Intestinal Microbiota and Growth in Offspring.
AB  - Previous studies suggest a link between intestinal microbiota and porcine feed
      efficiency (FE). Therefore, we investigated whether fecal microbiota
      transplantation (FMT) in sows and/or neonatal offspring, using inocula derived
      from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were
      assigned to control or FMT treatments and the subsequent offspring to control
      treatment, FMT once (at birth), or FMT four times (between birth and weaning).
      FMT altered sow fecal and colostrum microbiota compositions and resulted in
      lighter offspring body weight at 70 and 155 days of age when administered to sows
      and/or offspring. This was accompanied by FMT-associated changes within the
      offspring's intestinal microbiota, mostly in the ileum. These included
      transiently higher fecal bacterial diversity and load and numerous compositional
      differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes
      at high relative abundances and mostly members of Clostridia, respectively), as
      well as differences in the abundances of predicted bacterial pathways. In
      addition, intestinal morphology was negatively impacted, duodenal gene expression
      altered, and serum protein and cholesterol concentrations reduced due to FMT in
      sows and/or offspring. Taken together, the results suggest poorer absorptive
      capacity and intestinal health, most likely explaining the reduced body weight.
      An additive effect of FMT in sows and offspring also occurred for some
      parameters. Although these findings have negative implications for the practical
      use of the FMT regime used here for improving FE in pigs, they nonetheless
      demonstrate the enormous impact of early-life intestinal microbiota on the host
      phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel
      strategy to modulate the porcine intestinal microbiota in an attempt to improve
      FE in pigs. However, reprogramming the maternal and/or offspring microbiome by
      using fecal transplants derived from highly feed-efficient pigs did not
      recapitulate the highly efficient phenotype in the offspring and, in fact, had
      detrimental effects on lifetime growth. Although these findings may not be wholly
      attributable to microbiota transplantation, as antibiotic and purgative were also
      part of the regime in sows, similar effects were also seen in offspring, in which
      these interventions were not used. Nonetheless, additional work is needed to
      unravel the effects of each component of the FMT regime and to provide additional
      mechanistic insights. This may lead to the development of an FMT procedure with
      practical applications for the improvement of FE in pigs, which could in turn
      improve the profitability of pig production.

PMID- 29577088
TI  - Genome-Scale, Constraint-Based Modeling of Nitrogen Oxide Fluxes during Coculture
      of Nitrosomonas europaea and Nitrobacter winogradskyi.
AB  - Nitrification, the aerobic oxidation of ammonia to nitrate via nitrite, emits
      nitrogen (N) oxide gases (NO, NO2, and N2O), which are potentially hazardous
      compounds that contribute to global warming. To better understand the dynamics of
      nitrification-derived N oxide production, we conducted culturing experiments and
      used an integrative genome-scale, constraint-based approach to model N oxide gas
      sources and sinks during complete nitrification in an aerobic coculture of two
      model nitrifying bacteria, the ammonia-oxidizing bacterium Nitrosomonas europaea
      and the nitrite-oxidizing bacterium Nitrobacter winogradskyi. The model includes
      biotic genome-scale metabolic models (iFC578 and iFC579) for each nitrifier and
      abiotic N oxide reactions. Modeling suggested both biotic and abiotic reactions
      are important sources and sinks of N oxides, particularly under microaerobic
      conditions predicted to occur in coculture. In particular, integrative modeling
      suggested that previous models might have underestimated gross NO production
      during nitrification due to not taking into account its rapid oxidation in both
      aqueous and gas phases. The integrative model may be found at
      https://github.com/chaplenf/microBiome-v2.1. IMPORTANCE Modern agriculture is
      sustained by application of inorganic nitrogen (N) fertilizer in the form of
      ammonium (NH4+). Up to 60% of NH4+-based fertilizer can be lost through leaching
      of nitrifier-derived nitrate (NO3-), and through the emission of N oxide gases
      (i.e., nitric oxide [NO], N dioxide [NO2], and nitrous oxide [N2O] gases), the
      latter being a potent greenhouse gas. Our approach to modeling of nitrification
      suggests that both biotic and abiotic mechanisms function as important sources
      and sinks of N oxides during microaerobic conditions and that previous models
      might have underestimated gross NO production during nitrification.

PMID- 29577089
TI  - Mrgprs activation is required for chronic itch conditions in mice.
AB  - Introduction: Chronic itch has been drawing much attention due to its clinical
      significance and the complexity of its mechanisms. To facilitate the development
      of anti-itch strategies, it is necessary to investigate the key players in itch
      sensation under chronic itch conditions. Several members of the Mrgpr family were
      identified as itch receptors that detect cutaneous pruritogens in primary sensory
      neurons. However, the role of Mrgprs in chronic itch conditions has not been well
      described. Methods: Scratching behaviors of WT and Mrgpr-clusterDelta-/- mice
      were examined in dry skin model and contact dermatitis model to examine the role
      of Mrgpr genes in mediating chronic itch sensation. Scratching behaviors of the
      mice were also examined in allergic itch model. Real-time PCR were performed to
      examine the expression level of MrgprA3 and MrgprC11 under naive and dry skin
      conditions. The MrgprA3+ itch-sensing fibers were labeled by tdTomato
      fluorescence in Mrgpra3GFP-Cre; ROSA26tdTomato mice, and the morphology and
      density of those fibers in the epidermis were analyzed under dry skin condition.
      Results: We showed that deleting a cluster of Mrgpr genes in mice reduced
      scratching behavior severely under two chronic itch conditions, namely dry skin
      and contact dermatitis, and the allergic itch condition. Moreover, the gene
      expressions of itch receptors MrgprA3 and MrgprC11 in dorsal root ganglia (DRG)
      were upregulated significantly under dry skin condition. Consistently, the
      percentage of MrgprA3+ itch-sensing neurons was increased as well. We also
      observed hyperinnervation of MrgprA3+ itch-sensing fibers in the epidermis of the
      skin under dry skin condition. Discussion: We demonstrate that Mrgprs play
      important roles in mediating chronic itch and allergic itch. These findings
      enrich our knowledge of itch mechanism and may lead to the development of novel
      therapeutic approach to combat itch.

PMID- 29577090
TI  - A Hybrid Neural Network - World Cup Optimization Algorithm for Melanoma
      Detection.
AB  - One of the most dangerous cancers in humans is Melanoma. However, early detection
      of melanoma can help us to cure it completely. This paper presents a new
      efficient method to detect malignancy in melanoma via images. At first, the extra
      scales are eliminated by using edge detection and smoothing. Afterwards, the
      proposed method can be utilized to segment the cancer images. Finally, the extra
      information is eliminated by morphological operations and used to focus on the
      area which melanoma boundary potentially exists. To do this, World Cup
      Optimization algorithm is utilized to optimize an MLP neural Networks (ANN).
      World Cup Optimization algorithm is a new meta-heuristic algorithm which is
      recently presented and has a good performance in some optimization problems. WCO
      is a derivative-free, Meta-Heuristic algorithm, mimicking the world's FIFA
      competitions. World cup Optimization algorithm is a global search algorithm while
      gradient-based back propagation method is local search. In this proposed
      algorithm, multi-layer perceptron network (MLP) employs the problem's constraints
      and WCO algorithm attempts to minimize the root mean square error. Experimental
      results show that the proposed method can develop the performance of the standard
      MLP algorithm significantly.

PMID- 29577091
TI  - Early Administration of Venovenous Extracorporeal Life Support for Status
      Asthmaticus during Anaesthetic Induction: Case Report and Literature Review.
AB  - Here we report a case of a 40-year-old man who visited the emergency room with
      severe chest pain. He showed a Stanford type B aortic dissection on chest
      computed tomography. Despite medical treatment and malperfusion of lower
      extremities, acute renal failure developed; hence thoracic endovascular aortic
      repair (TEVAR) was considered under general anaesthesia. After endotracheal
      intubation, ventilation with low tidal volume required high inspiratory airway
      pressure. An arterial blood gas analysis showed PaCO2 of 61.8mmHg and PaO2 of
      26.4mmHg, indicating a status asthmaticus of hypoxaemia and hypercarbia, which
      did not respond to bronchodilator or mechanical ventilation. Impending cardiac
      arrest was treated using venovenous extracorporeal life support, which was
      administered by percutaneous femoral cannulation. Surgical procedure was
      completed without any complications. Extracorporeal life support was weaned at
      one day after the operation. The patient was discharged without any
      complications.

PMID- 29577092
TI  - Assessment of Maximal Isometric Hand Grip Strength in School-aged Children.
AB  - Background: Hand grip strength (HGS) test is commonly used as an indicator of
      overall muscle strength in medical and sport practices. Recently, several studies
      have proposed that the measurement of the maximal HGS depends on dynamometer's
      handle position. The aim of the present study was to identify the optimal handle
      position to obtain maximal HGS using the hand grip dynamometer (HGD) for school
      aged children. Methods: HGS was assessed with the Jamar digital HGD. Each
      participant performed three maximum contractions of each hand on three handle
      positions progressing from first to third position. Results: A total of 135
      healthy children aged 5-9 years participated in the study. Participants obtained
      significantly higher results using position 2 than using positions 1 or 3. The
      maximal mean (+/- SD) HGS achieved was 9.9 (+/- 3.1) kg with position 1, 10.4 (+/
      3.1) kg with position 2, and 9.0 (+/- 3.2) kg with position 3. Handle position 2
      was the most comfortable position for 73% of participants. Conclusions: Our
      results provide useful methodological information indicating that the second
      handle position of the Jamar digital HGD is optimal to measure maximal HGS in non
      athletic healthy pediatric participants aged 5-9 years.

PMID- 29577093
TI  - Evaluation of a Neurokinin-1 Antagonist in Preventing Multiple-day Cisplatin
      induced Nausea and Vomiting.
AB  - Objective: To perform a prospective non-randomized comparison of the
      effectiveness and safety of combined neurokinin-1 antagonist aprepitant treatment
      with the standard multiple-day cisplatin regimen for the prevention of cisplatin
      induced nausea and vomiting (CINV). Methods: Patients being administered 3-day
      cisplatin-based chemotherapy (25 mg/m2/d) who had never received aprepitant were
      given either the standard regimen (tropisetron and dexamethasone) or the
      aprepitant regimen (aprepitant plus tropisetron and dexamethasone). The primary
      endpoint was the complete response (CR) in the overall phase (OP, 0-120 h)
      between the combined aprepitant triple regimen group and the standard group.
      Secondary endpoints were the CR in the acute phase (AP, 0-24 h) and delay phase
      (DP, 25-120 h) between the two groups. The first time of vomiting was also
      compared by Kaplan-Meier curves. The impact of CINV on the quality of life was
      assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse
      effects (AEs) were also recorded. Results: A CR was achieved by 80.0% in the
      aprepitant group compared with 56.0% in the standard group during the OP (P
      =0.018)as well as during the DP. However, during the AP, the aprepitant and
      standard therapy groups achieved identical CR rates (98.0%, P =1.000). A longer
      time to first emesis was documented for the aprepitant group than for the
      standard group. No effect of CINV on quality of life as assessed by FLIE was
      reported by 44.7% of aprepitant therapy patients and 24.0% of standard therapy
      patients (P=0.035). The main aprepitant-related AEs were fatigue and
      constipation, but there was no significant difference between groups. Conclusion:
      Combined aprepitant therapy is recommended for the prevention of multiple-day
      CINV because of its improved CINV control rate and safety.

PMID- 29577094
TI  - Value of Continuous Video EEG and EEG Responses to Thermesthesia Stimulation in
      Prognosis Evaluation of Comatose Patients after Cardiopulmonary Resuscitation.
AB  - Objective: To investigate the clinical value of video-electroencephalography
      (VEEG) and thermal stimulus on evaluating the prognosis of comatose patients
      after cardiopulmonary resuscitation. Methods: Twenty eight comatose patients with
      cardiopulmonary resuscitation were included in the department of ICU of the First
      Teaching Hospital of Fujian Medical University from February 2013 to March 2016.
      Of the included 28 patients, 20 cases died (death group) and 8 cases survived
      (survival group) after cardiopulmonary resuscitation. The VEEG, Glasgow Coma
      Scale (GCS) and APACHE II score were recorded and compared between the death and
      survival group. The prediction value of death for VEEG, GCS and APACHE II were
      evaluated through sensitivity, specificity and area under the receiver operating
      characteristic (ROC) curve (AUC). Results: GCS and APACHEH II score were
      statistical different between the death and survival group (P<0.05). With the
      increase of VEEG grading, the mortality rate of patients increased significantly
      (P<0.05). Predicting value of mortality for GCS, VEEG and APACHEH II were 57.69%,
      61.54% and 71.43% respectively without statistical difference (P>0.05). The death
      prediction sensitivity and specificity for GCS were 67.0% and 85.0%, for APACHEH
      II were 95.1% and 85.0%, for VEEG were 100.0% and 85.2%. VEEG has the highest
      sensitivity, Specificity, coincidence rate and Kappa vale compared to GCS, and
      APACHEH II. Conclusion: Video-electroencephalography is a useful tool for
      predicting the death risk for patients who received cardiopulmonary
      resuscitation.

PMID- 29577095
TI  - Rapid neuroadaptation to surgically-induced aniseikonia in a 17-year-old patient
      with high preoperative anisometropia: A case report.
AB  - Purpose: To report a case of rapid neuroadaptation to surgically-induced
      aniseikonia in a 17-year-old with preoperative anisometropia of 9.5 D.
      Observations: A 17-year-old female with a history of retinopathy of prematurity
      (ROP) and progressive high myopia with resulting anisometropia secondary to
      conventional laser photocoagulation in her right eye was found to have diplopia
      after undergoing cataract surgery in that eye. Other etiologies of diplopia were
      ruled out and reversal of anisometropia remained the only viable diagnosis. Her
      diplopia fully resolved without intervention within one month of the surgery.
      Conclusion and Importance: In cases of neuroadaptation to long standing
      anisometropia, even if that anisometropia develops in infancy, abrupt reversal
      following surgery can be surprisingly well tolerated.

PMID- 29577096
TI  - Intravitreal rituximab for the treatment of a secondary intraocular relapse of a
      large B-cell lymphoma.
AB  - Purpose: To report a rare case of secondary intraocular lymphoma treated with
      intravitreal rituximab, following pars plana vitrectomy. Observations: A 74-year
      old female with history of parotid gland large B-cell lymphoma presented
      bilateral intraocular recurrence 10 years after the onset of the primary
      malignancy. Systemic work-up including PET/CT Scan, bone marrow biopsy, brain MRI
      and CSF analysis were unremarkable, and the patient declined to undergo systemic
      chemotherapy. Vision loss in her left eye was severe due to significant sub
      retinal pigment epithelium (RPE) infiltration involving the macula; this eye was
      treated with external beam radiation therapy. On the right eye, the relapse
      manifested with vitreous involvement and fovea-sparing multifocal, sub-RPE
      infiltration for which the patient received monthly intravitreal rituximab
      injections, following pars plana vitrectomy. Through the course of therapy, the
      patient achieved good local control and maintained 20/20 visual acuity on her
      right eye. Brain magnetic resonance imaging (MRI) surveillance, every 3 months,
      was performed and revealed a cerebellar recurrence 24 months into the course of
      therapy. Conclusions and importance: Our case illustrates how intravitreal
      immunotherapy with rituximab may provide local control of CD-20 positive
      secondary intraocular lymphoma; particularly in cases where systemic therapy is
      not amenable. In our case, a prior vitrectomy, did not appear to interfere with
      the therapeutic effect of intravitreal rituximab. Close quarterly surveillance
      with Brain MRI may help disclose central nervous system recurrences in such
      cases.

PMID- 29577097
TI  - Traumatic subhyaloid macular hemorrhage with complete resolution following
      Neodymium-Doped Yttrium Aluminium Garnet Laser.
AB  - Purpose: To report a case of traumatic subhyaloid macular hemorrhage with severe
      sudden vision loss treated successfully with Neodymium-Doped Yttrium Aluminium
      Garnet Laser (Nd:YAG laser). Observations: A 16-year-old boy presented to the eye
      clinic with acute vision loss secondary to blunt trauma by a stone to his left
      eye 3 days prior to consultation that caused subhyaloid macular hemorrhage.
      Nd:YAG laser was performed to open the hyaloid membrane and allow the blood to
      diffuse into the vitreous cavity and be absorbed. The patient demonstrated
      complete recovery as his visual acuity went from counting fingers to 20/20 within
      20 days. No complications due to the treatment were reported. Conclusions and
      importance: To the best of our knowledge, there have been no reported cases of
      subhyaloid macular hemorrhage treated with Nd:YAG laser in which the etiology was
      trauma and showed full, rapid recovery with no sequelae.

PMID- 29577098
TI  - Pericentral hydroxychloroquine retinopathy in a Caucasian female.
AB  - Purpose: To report a rare presentation of the pericentral pattern of
      hydroxychloroquine (HCQ) retinal toxicity in a Caucasian female. Observations:
      The patient presented with 20 years of exposure to HCQ, at a daily dose of
      5.2mg/kg of actual body weight, and manifested a pericentral-only phenotype of
      HCQ toxicity, as demonstrated with detailed structural and functional testing.
      Conclusions and importance: Although rare, the pericentral pattern of HCQ
      toxicity may occur in Caucasian patients in the absence of paracentral changes.

PMID- 29577099
TI  - Bilateral superior rectus transposition and medial rectus recession for bilateral
      sixth nerve palsy.
AB  - Purpose: To present the results of bilateral superior rectus transposition with
      medial rectus recession in a case of chronic bilateral sixth nerve palsy.
      Observation: Bilateral superior rectus transposition with medial rectus recession
      resulted in full correction of esotropia with resolution of horizontal diplopia,
      improvement in abduction, and regain of stereoacuity in our case. There was
      minimal limitation of adduction, with no abnormal vertical or torsional changes.
      Conclusion and importance: Bilateral superior rectus transposition with medial
      rectus recession appears to be a useful procedure for surgical treatment of
      bilateral sixth nerve palsy with minimal side effects. Given its potential for
      reduced risk of anterior segment ischemia (ASI), it may have especially good
      value in the select group of patients at risk for ASI. Studies with larger sample
      size and longer follow up are needed to further evaluate this procedure and
      elucidate the variables in surgical technique for superior rectus transposition.

PMID- 29577100
TI  - Lagophthalmos caused by cicatricial adhesion of orbital adipose tissue to orbital
      roof: A case report.
AB  - Purpose: To report a case of lagophthalmos caused by cicatricial adhesion of
      orbital adipose tissue to the orbital roof. Observations: A 23-year-old female
      was presented with right lagophthalmos. Five months prior to consult at our
      clinic, she suffered from a penetrating trauma to the frontal lobe of the brain
      through the right orbital roof with cerebrospinal fluid leakage. Decompressive
      craniectomy was performed immediately after the injury using a coronal incision,
      which was followed by reconstruction with an artificial bone 1 month later. On
      examination at our clinic, she showed right exposure keratopathy with best
      corrected visual acuity of 20/100 due to corneal opacity. The palpebral
      contracted scar was first elongated using Z-plasty technique but excursion of the
      upper eyelid under a finger force assistance was insufficient to eliminate
      lagophthalmos. However, complete eyelid closure under a finger force assistance
      was achieved after sharp dissection of the cicatrized adipose tissue from the
      orbital roof. An autogenous dermis-fat was grafted on the orbital roof and
      superior orbital rim to avoid adhesion of orbital adipose tissue onto the bone
      again. Conclusion and importance: Cicatricial adhesion of an orbital adipose
      tissue to the orbital roof is one of the possible causes of posttraumatic
      lagophthalmos in patients with an orbital roof fracture. Surgeons need to be
      aware of this condition in planning of surgical repair when such a fracture is
      encountered.

PMID- 29577101
TI  - Management of recalcitrant polypoidal choroidal vasculopathy by feeder vessel
      laser photocoagulation.
AB  - Purpose: To describe management of residual branch vascular network (BVN) in
      polypoidal choroidal vasculopathy (PCV) by thermal laser photocoagulation of
      feeder vessel. Observations: Case report of sixty-four year old female with
      polypoidal choroidal vaculopathy (PCV) with moderate response to seven doses of
      intravitreal ranibizumab, six doses of intravitreal bevacizumab and one session
      of photodynamic therapy (PDT). The patient has resolved polyps but persistence of
      disease activity due to residual BVN and large pigment epithelial detachment
      (PED). Patient underwent thermal laser photocoagulation of feeder vessel of BVN
      identified on indocyanine green angiography (ICGA). There was complete resolution
      of residual BVN and large PED, which was confirmed on ICGA. Conclusions and
      Importance: Recalcitrant cases of PCV without polyps but having BVN with feeder
      vessel can be managed by ICGA guided thermal laser photocoagulation. The case
      report illustrates the importance of utilizing multimodal imaging such as video
      indocyanine green angiography (ICGA) for identification of feeder vessel and its
      deployment for optimal management of refractory PCV.

PMID- 29577102
TI  - A case with corneal perforation due to bacterial concretion derived from lacrimal
      canaliculitis.
AB  - Purpose: To report a case with corneal perforation, presumably due to ocular
      cicatricial pemphigoid (OCP) and bacterial concretion derived from lacrimal
      canaliculitis. Observations: A patient with OCP demonstrated adherence of
      concretion to the cornea of her right eye. She also demonstrated canaliculitis in
      this eye. We removed a whitish precipitate from the bottom of the corneal ulcer.
      When we flushed her lacrimal pathway, a marked amount of bacterial concretion and
      dense mucosa were refluxed from both puncta on the right side. On the next day,
      corneal perforation was visible from the area where concretion was removed. We
      performed punctoplasty and removed the bacterial concretion from the lacrimal
      canaliculus and sac. After the operation, her symptoms improved and corneal
      perforation recovered. Conclusions and Importance: Both lacrimal canaliculitis
      and OCP can cause corneal perforation, and adherence of bacterial concretion onto
      the cornea is very rare. However, once it occurs, corneal perforation can rapidly
      follow. OCP sometimes causes corneal epithelial damage, which may influence
      adherence to concretion. Canaliculitis in patients with OCP should be managed
      carefully.

PMID- 29577103
TI  - Traumatic chiasmal syndrome: A meta-analysis.
AB  - Purpose: To report a case presenting with bitemporal hemianopia due to traumatic
      chiasmal syndrome after head injury, and to compare the findings with individual
      case reports published in the literature. Methods: A detailed search was made in
      PubMed, MedIND, Taylor and Francis online and Wiley online library databases for
      individual case reports of traumatic chiasmal syndrome. All the case reports were
      read in full and the findings summarized in a table, which included details of
      the case who presented with bitemporal hemianopia as an index case. Results: All
      published cases of traumatic chiasmal syndrome appear to share some common
      features, such as injury to the frontal bone and fracture of the anterior skull
      base. Bitemporal hemianopia and visual acuity have a variable presentation, and
      do not appear to correlate with severity of injury. Isolated bitemporal
      hemianopia is rare and clinical improvement may or may not occur. Conclusions and
      importance: Traumatic chiasmal syndrome should be considered as a differential
      diagnosis in patients presenting with bitemporal hemianopia after head injury
      causing frontal and anterior skull base fracture.

PMID- 29577104
TI  - A new worm infiltrating the human cornea: A report of three cases.
AB  - Purpose: To characterize a new species of parasitic nematode that triggers
      uveitis. Observations: Three previously healthy, relatively young people each
      contracted a corneal stromal nematode that, upon surgical removal and
      examination, did not match any known nematodes. Clinical ocular findings included
      corneal opacification, visible corneal worms, conjunctival injection, and
      uveitis. Conclusions and Importance: The three cases presented here represent a
      previously undescribed parasitic infection of the cornea by an unidentified
      nematode. These findings may represent a previously unrecognized zoonotic
      infection from wildlife sources and potentially a newly documented nematode
      requiring description. Future clinical findings regarding this newly described
      nematode are needed to further develop our understanding of the disease.

PMID- 29577105
TI  - Immune responses to engineered nanomaterials: current understanding and
      challenges.
AB  - Engineered nanomaterials (ENM) are utilized in many applications due to their
      unique physicochemical properties. The increasing use of ENMs in consumer
      products raises concerns of potential adverse effects in humans and the
      environment. A common outcome of exposure (intentional, environmental or
      occupational) to ENMs is altered immune responses including inflammation,
      hypersensitivity, and immunosuppression. ENMs have been shown to interact with
      the immune system through key effector cells (i.e. mast cells and antigen
      presenting cells) or via complement activation leading to consequences to both
      innate and adaptive immunity. Further, upon introduction into a biological
      system, ENMs are rapidly coated with proteins, lipids and other macromolecules
      forming a biocorona which impacts immune cell and complement responses. In this
      current opinion, we highlight key studies and challenges in understanding
      cellular mechanisms of ENM-mediated immunomodulation and toxicity.

PMID- 29577106
TI  - Modeling Bloch oscillations in nanoscale Josephson junctions.
AB  - Bloch oscillations in nanoscale Josephson junctions with a Coulomb charging
      energy comparable to the Josephson coupling energy are explored within the
      context of a model previously considered by Geigenmuller and Schon that includes
      Zener tunneling and treats quasiparticle tunneling as an explicit shot-noise
      process. The dynamics of the junction quasicharge are investigated numerically
      using both Monte Carlo and ensemble approaches to calculate voltage-current
      characteristics in the presence of microwaves. We examine in detail the origin of
      harmonic and subharmonic Bloch steps at dc biases I = (n/m)2ef induced by
      microwaves of frequency f and consider the optimum parameters for the observation
      of harmonic (m = 1) steps. We also demonstrate that the GS model allows a
      detailed semiquantitative fit to experimental voltage-current characteristics
      previously obtained at the Chalmers University of Technology, confirming and
      strengthening the interpretation of the observed microwave-induced steps in terms
      of Bloch oscillations.

PMID- 29577107
TI  - Vitamin D Supplementation in Patients With Type 2 Diabetes: The Vitamin D for
      Established Type 2 Diabetes (DDM2) Study.
AB  - Context: Observational data support a role for vitamin D in type 2 diabetes, but
      evidence from trials is inconclusive. Objective: To evaluate the effect of
      vitamin D supplementation on beta-cell function and hemoglobin A1c (HbA1c) in
      patients with well-controlled type 2 diabetes. Design: Double-blind, randomized,
      placebo-controlled clinical trial. Setting: Tufts Medical Center, Boston, MA; VA
      Medical Center, Cincinnati, OH. Participants: A total of 127 patients (mean age,
      60 years) with stable (HbA1c <=7.5%) diabetes managed with lifestyle only or
      lifestyle plus metformin. Intervention: Subjects were given 4000 units of vitamin
      D3 (cholecalciferol) daily or placebo for 48 weeks. Main Outcome Measure: Insulin
      secretion rate (ISR) was estimated from peripheral plasma C-peptide levels after
      a 3-hour 75-g oral glucose tolerance test done at baseline and week 24. Changes
      in HbA1c were assessed at 16, 24, 36, and 48 weeks. Results: Baseline mean plasma
      25-hydroxyvitamin D [25(OH)D] concentration was 26.6 ng/mL, mean HbA1c was 6.6%,
      and 78% of patients were on metformin. At week 24, mean 25(OH)D changed by 20.5
      and -1.6 ng/mL in the vitamin D and placebo groups, respectively (P < 0.001). The
      vitamin D and placebo groups did not differ in change in ISR or HbA1c. Among
      patients treated with lifestyle only (n = 28), vitamin D supplementation reduced
      HbA1c compared with placebo (-0.1% vs 0.3%, respectively; P = 0.034) at week 24.
      This result was not observed at the other time points and could be due to chance.
      Conclusion: Vitamin D3 at 4000 IU/d did not change ISR or HbA1c in patients with
      well-controlled type 2 diabetes on metformin not selected for vitamin D
      deficiency.

PMID- 29577108
TI  - Testosterone and All-Cause Mortality in Older Men: The Role of Metabolic
      Syndrome.
AB  - Previous studies have shown controversial results about the role of testosterone
      in all-cause mortality in elderly men. We hypothesized that metabolic syndrome
      (MetS) could partly explain this discrepancy. We therefore examined the
      association of all-cause mortality with total and bioavailable testosterone,
      taking into account the MetS. We used data from the Three-City Cohort (3C) study
      with 12-year follow-up. The 3C study included 3650 men aged >65 years in three
      French cities. Hormone was measured in a random subsample of 444 men, and MetS
      was determined as stated by the International Diabetes Federation criteria. We
      used inverse-probability-weighted Cox regression to estimate hazard ratios (HRs)
      and 95% confidence intervals (95% CIs). Of 444 men included in the analysis, 106
      (23.9%) had MetS at baseline, and 166 died over the follow-up. There was a
      significant interaction between testosterone level and MetS for all-cause
      mortality (P = 0.002 and P = 0.008 for total and bioavailable testosterone,
      respectively). Among men with MetS, a decrease in one standard deviation of
      testosterone was associated with higher mortality risk [HR 1.78 (95% CI 1.13 to
      2.78) and HR 1.83 (95% CI 1.17 to 2.86) for total and bioavailable testosterone,
      respectively]. By contrast, there was no association of testosterone with
      mortality risk among men without MetS. Our results suggest that MetS modifies the
      association between testosterone and mortality in older men. If confirmed, these
      findings could contribute to improve risk stratification and better manage the
      health of older men.

PMID- 29577109
TI  - Male Mice Lacking NLRX1 Are Partially Protected From High-Fat Diet-Induced
      Hyperglycemia.
AB  - Nod-like receptor (NLR)X1 is an NLR family protein that localizes to the
      mitochondrial matrix and modulates reactive oxygen species production, possibly
      by directly interacting with the electron transport chain. Recent work
      demonstrated that cells lacking NLRX1 have higher oxygen consumption but lower
      levels of adenosine triphosphate, suggesting that NLRX1 might prevent uncoupling
      of oxidative phosphorylation. We therefore hypothesized that NLRX1 might regulate
      whole-body energy metabolism through its effect on mitochondria. Male NLRX1 whole
      body knockout (KO) mice and wild-type (WT) C57BL/6N controls were fed a low-fat
      or a high-fat (HF) diet for 16 weeks from weaning. Contrary to this hypothesis,
      there were no differences in body weight, adiposity, energy intake, or energy
      expenditure between HF-fed KO and WT mice, but instead HF KO mice were partially
      protected from the development of diet-induced hyperglycemia. Additionally, HF KO
      mice did not present with hyperinsulinemia during the glucose tolerance test, as
      did HF WT mice. There were no genotype differences in insulin tolerance, which
      led us to consider a pancreatic phenotype. Histology revealed that KO mice were
      protected from HF-induced pancreatic lipid accumulation, suggesting a potential
      role for NLRX1 in pancreatic dysfunction during the development diet-induced type
      2 diabetes mellitus. Hence, NLRX1 depletion partially protects against
      postabsorptive hyperglycemia in obesity that may be linked to the prevention of
      pancreatic lipid accumulation. Although the actual mechanisms restoring glucose
      and insulin dynamics remain unknown, NLRX1 emerges as a potentially interesting
      target to inhibit for the prevention of type 2 diabetes mellitus.

PMID- 29577110
TI  - Health and Cardiometabolic Disease in Transgender Adults in the United States:
      Behavioral Risk Factor Surveillance System 2015.
AB  - Context: Little is known about the health of transgender adults in the United
      States, a growing population. There have been no large reports examining
      differences in health status and cardiometabolic disease in subgroups of
      transgender adults [female-to-male (FTM), male-to-female (MTF), and gender
      nonconforming (GNC)] in the United States. Objective: Compare the health status
      and prevalence of cardiometabolic disease among specific subgroups of transgender
      adults (FTM, MTF, GNC) with those of cisgender adults in the United States.
      Design: Secondary data analysis based on the 2015 Behavioral Risk Factor
      Surveillance System survey. Setting: The 22 states in the United States that
      asked about transgender identity. Participants: Noninstitutionalized adults age
      >=18 years who reside in the United States, identified through telephone-based
      methods. Main Outcome Measures: Data were extracted for respondents who answered
      the transgender identity question. Weighted percentages are given for all
      measures. Adjusted odds ratios (ORs) are reported for health status and
      cardiometabolic disease measures. Results: FTM adults have a higher odds of being
      uninsured than both cisgender women [OR 3.8; 95% confidence interval (CI), 2.1 to
      7.1] and cisgender men (OR 2.5; 95% CI, 1.4 to 4.7). MTF adults have a higher
      odds of reporting myocardial infarction than cisgender women (OR 2.9; 95% CI, 1.6
      to 5.3) but not cisgender men. Conclusions: There are significant differences in
      health status measures and cardiometabolic health between subgroups of
      transgender adults and cisgender adults. There is a need for additional research
      to understand the societal and medical (e.g., hormone therapy) effects on these
      outcomes.

PMID- 29577111
TI  - Phosphorus Balance in Adolescent Girls and the Effect of Supplemental Dietary
      Calcium.
AB  - There are limited data on phosphorus balance and the effect of dietary calcium
      supplements on phosphorus balance in adolescents. The purpose of this study was
      to determine phosphorus balance and the effect of increasing dietary calcium
      intake with a supplement on net phosphorus absorption and balance in healthy
      adolescent girls. This study utilized stored urine, fecal, and diet samples from
      a previously conducted study that focused on calcium balance. Eleven healthy
      girls ages 11 to 14 years participated in a randomized crossover study, which
      consisted of two 3-week periods of a controlled diet with low (817 +/- 19.5 mg/d)
      or high (1418 +/- 11.1 mg/d) calcium, separated by a 1-week washout period.
      Phosphorus intake was controlled at the same level during both placebo and
      calcium supplementation (1435 +/- 23.5 and 1453 +/- 28.0 mg/d, respectively, p =
      0.611). Mean phosphorus balance was positive by about 200 mg/d and was unaffected
      by the calcium supplement (p = 0.826). Urinary phosphorus excretion was lower
      with the calcium supplement (535 +/- 42 versus 649 +/- 41 mg/d, p = 0.013), but
      fecal phosphorus and net phosphorus absorption were not significantly different
      between placebo and calcium supplement (553 +/- 60 versus 678 +/- 63 versus mg/d,
      p = 0.143; 876 +/- 62 versus 774 +/- 64 mg/d, p = 0.231, respectively). Dietary
      phosphorus underestimates using a nutrient database compared with the content
      measured chemically from meal composites by ~40%. These results show that
      phosphorus balance is positive in girls during adolescent growth and that a
      calcium dietary supplement to near the current recommended level does not affect
      phosphorus balance when phosphorus intake is at 1400 mg/d, a typical US intake
      level.

PMID- 29577112
TI  - A phenomenological study of business graduates' employment experiences in the
      changing economy.
AB  - This study explores the perspectives of business college graduates, how
      technology has shaped the structures of their jobs, and the role of non-technical
      skills as they navigate the changing career path. Three overlapping themes
      emerged from the data analysis: (1) influence of increased technology
      capabilities on job structures and careers; (2) participation in job-related
      training and formal education as means of adapting to the new work environment;
      and (3) the role of non-technical skills in the workplace amidst the
      intensification of technology change. This research provides higher education
      practitioners and labor market researchers qualitative perspectives on work
      structure changes.

PMID- 29577113
TI  - STAT1 Is Required for Suppression of Type 17 Immunity during Influenza and
      Bacterial Superinfection.
AB  - Influenza is an annual, global health care concern. Secondary bacterial pneumonia
      is a severe complication associated with primary influenza virus infection, often
      resulting in critical morbidity and mortality. Our laboratory has identified
      influenza-induced suppression of anti-bacterial Type 17 immunity as a mechanism
      for enhanced susceptibility to bacterial super-infection. We have shown that
      influenza-induced type I interferon impairs Type 17 activation. STAT1 is a
      transcription factor involved in interferon signaling, shared by type I, II, and
      III interferon. In this work, we investigated the role of STAT1 signaling during
      influenza, methicillin-resistant Staphylococcus aureus (MRSA) super-infection.
      STAT1-/- mice had increased morbidity and airway inflammation compared to control
      mice during influenza mono-infection. Despite this worsened anti-viral response,
      STAT1-/- mice were protected from super-infection bacterial burden and mortality
      compared to controls. Type 17 immune activation was increased in lymphocytes in
      STAT1-/- mice during super-infection. The elevation in Type 17 immunity was not
      related to increased IL-23 production, as type I interferon could inhibit IL-23
      expression in a STAT1 independent manner. STAT1-/- antigen presenting cells were
      inherently biased towards Type 17 polarization compared to control cells.
      Further, STAT1-/- dendritic cells produced attenuated IL-6 and TNFalpha upon heat
      killed S. aureus stimulation compared to control. Overall, these data indicate
      that STAT1 signaling plays a detrimental role in influenza, MRSA super-infection
      by controlling the magnitude of Type 17 immune activation.

PMID- 29577114
TI  - Patterns of Statin Use in Older Medicare Beneficiaries With Traumatic Brain
      Injury.
AB  - Background: In addition to lowering lipids, statins also may be beneficial for
      older adults sustaining a traumatic brain injury (TBI), as statin use prior to
      and following trauma may decrease mortality following injury. However, despite
      statins' potential to reduce mortality, there is limited research regarding
      statin use among older adults. Objective: To characterize and investigate factors
      associated with statin use among older adults with TBI. Methods: A retrospective
      drug utilization study was used to characterize statin use among Medicare
      beneficiaries 65 and older hospitalized with a TBI during 2006 to 2010 and with
      continuous Medicare Parts A, B, and D coverage 6 months prior and 12 months
      following TBI. Logistic regression was used to investigate the factors associated
      with statin use. The exposure of interest was statin use prior to and following
      TBI. Results: Of the 75 698 beneficiaries included in the study, 37 874 (~50%) of
      beneficiaries used a statin at least once during the study period. The most
      common statin used was simvastatin, while fluvastatin was the least used statin.
      Statin users were more likely to have cardiovascular diseases when compared to
      nonusers. Hyperlipidemia was a major factor associated with statin use and had
      the greatest impact on statin use compared to nonuse (odds ratio = 9.54; 95%
      confidence interval = 9.07, 10.03). Conclusions: This national sample of older
      adults with TBI suggests that statins are commonly used. Future studies must next
      examine the impact of statin use on mortality and secondary injury in order to
      shape pharmacological therapy guidelines following TBI.

PMID- 29577115
TI  - Neighborhood Matching for Curved Domains with Application to Denoising in
      Diffusion MRI.
AB  - In this paper, we introduce a strategy for performing neighborhood matching on
      general non-Euclidean and non-flat domains. Essentially, this involves
      representing the domain as a graph and then extending the concept of convolution
      from regular grids to graphs. Acknowledging the fact that convolutions are
      features of local neighborhoods, neighborhood matching is carried out using the
      outcome of multiple convolutions at multiple scales. All these concepts are
      encapsulated in a sound mathematical framework, called graph framelet transforms
      (GFTs), which allows signals residing on non-flat domains to be decomposed
      according to multiple frequency subbands for rich characterization of signal
      patterns. We apply GFTs to the problem of denoising of diffusion MRI data, which
      can reside on domains defined in very different ways, such as on a shell, on
      multiple shells, or on a Cartesian grid. Our non-local formulation of the problem
      allows information of diffusion signal profiles of drastically different
      orientations to be borrowed for effective denoising.

PMID- 29577116
TI  - Probing the swelling-dependent mechanical and transport properties of
      polyacrylamide hydrogels through AFM-based dynamic nanoindentation.
AB  - Hydrogels are composed of a crosslinked polymer network and water. The
      constitutive behaviors of hydrogels have been modeled based on Flory-Huggins
      theory. Within this model, the thermodynamic and kinetic parameters are assumed
      to be of constant values and are typically characterized through swelling tests.
      Since most hydrogels can absorb a large amount of solvent from the dry state to
      the swollen state, and the network size and solvent concentration of the
      hydrogels change significantly, the assumption of constant values of the
      thermodynamic and kinetic properties as the network swells is questionable. In
      this work, we have experimentally shown that even for the simple neutral
      polyacrylamide (PAAm) hydrogels, their mechanical responses cannot be fully
      described by the Flory-Huggins theory with constant thermodynamic parameters: N
      (number of chains per unit volume of dry polymers) and chi (polymer-solvent
      interaction parameter). For a more complete and precise characterization of the
      hydrogels, we measure the evolving properties of the gels as the network swells.
      Here, we use dynamic indentation to measure the poroelastic properties (shear
      modulus G, Poisson's ratio nu and diffusivity D) of the hydrogels under a wide
      range of swelling ratios. We also use linear perturbation to build the link
      between G, nu and N, chi, and plot the thermodynamic parameters in the Flory
      Huggins theory as a function of the hydrogel swelling ratio. Consequently, the
      validity of the hydrogel models based on Flory-Huggins theory can be
      quantitatively examined.

PMID- 29577117
TI  - Modulation of whey protein-kappa carrageenan hydrogel properties via enzymatic
      protein modification.
AB  - Treatment of whey protein isolate (WPI; 1 to 25% w/w) in heated kappa-carrageenan
      (KC; 2% w/w) slurries with protease and/or transglutaminase modulated the
      properties of the hydrogels formed after cooling. Observation of peak compression
      stress and strain at gel rupture showed WPI incorporation at 1, 5 and 10% (w/w)
      significantly reduced the strength and deformability of 2% (w/w) KC gels.
      Treatment of WPI solutions in KC slurries with Alcalase 2.4L was shown by both
      SDS-Page and size exclusion HPLC to reduce protein/peptide molecular weight
      distributions below 10 kDa, with large portions below 1 kDa. This peptide size
      reduction within the KC matrix produced more translucent gels with a more
      organized wall and cell structure as observed by SEM, which resulted in gels with
      observed rupture stress/strain levels similar to 2% KC alone. Transglutaminase
      treatment of WPI-KC slurries showed the reverse behavior, reducing gel
      translucency, strength and deformability. At these loadings, WPI-KC gel
      strength/deformability appears to relate decreasing peptide size to gel behavior
      trending towards KC-only gels; suggesting peptide size modulation in protein
      carbohydrate complexes will allow significant tailoring of texture for the
      delivery of protein/peptide rich gelled products.

PMID- 29577118
TI  - Carbon nanotube-copper ferrite-catalyzed aqueous 1,3-dipolar cycloaddition of in
      situ-generated organic azides with alkynes.
AB  - A novel nanohybrid catalyst was developed by assembling copper ferrite
      nanoparticles on carbon nanotubes. The supramolecular catalyst was applied to the
      one-pot azidation/1,3-dipolar cycloaddition of various substrates, at room
      temperature, and in an aqueous medium. The nanohybrid could also be recycled and
      reused by means of magnetic recovery.

PMID- 29577119
TI  - Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through
      mitochondrial/caspase-mediated pathways.
AB  - Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease associated
      with a potential imbalance between the growth and death of rheumatoid arthritis
      fibroblast-like synoviocytes (RA-FLSs). Imperatorin (IPT) is a naturally
      occurring furanocoumarin found in umbelliferous vegetables, citrus fruits, and
      some herbs. The effects of IPT on the proliferation and apoptosis of RA-FLSs and
      its potential underlying mechanisms have remained unclear. RA-FLSs obtained from
      RA patients were induced by interleukin-1beta (IL-1beta) and treated with IPT.
      Cell viability was determined by MTT assay. Apoptotic cell death was analyzed by
      Annexin V-FITC/PI double staining and Hoechst 33342 staining. The loss in the
      mitochondrial membrane potential (DeltaPsim) was visualized on the basis of JC-1
      staining via fluorescence microscopy, and protein expression changes were
      assessed by western blot, whereas in vivo studies were conducted in male Wistar
      rats followed by histopathological assessment via TUNEL assay and HE staining of
      tissues. The results showed that IPT significantly reduced cell viability,
      accelerated cell apoptosis and decreased matrix metalloproteinases-1/-3
      expression in IL-1beta-induced RA-FLSs. Furthermore, IPT exposure was found to
      disrupt the DeltaPsim compared to the IL-1beta-induced treatment. Moreover, IPT
      increased the release of mitochondrial cytochrome C, the ratio of Bax/Bcl-2, and
      the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In vivo
      studies showed that IPT not only significantly reduced the collagen induced
      arthritis by reducing synovial hyperplasia, and pannus formation but also
      enhanced the apoptotic index of ankle joint cells. Conclusively, our findings
      suggest that IPT inhibits cell proliferation and induces apoptosis in RA-FLSs
      that may be associated with mitochondrial/caspase-mediated signalling pathways.

PMID- 29577120
TI  - In vitro and environmental toxicity of reduced graphene oxide as an additive in
      automotive lubricants.
AB  - Despite the ground-breaking potential of nanomaterials, their safe and
      sustainable incorporation into an array of industrial markets prompts a deep and
      clear understanding of their potential toxicity for both humans and the
      environment. Among the many materials with great potential, graphene has shown
      promise in a variety of applications; however, the impact of graphene based
      products on living systems remains poorly understood. In this paper, we
      illustrate that via exploiting the tribological properties of graphene
      nanosheets, we can successfully improve both the frictional behaviour and the
      anti-wear capacity of lubricant oil for mechanical transmission. By virtue of
      reducing friction and enhancing lubricant lifetimes, we can forecast a reduction
      in friction based energy loss, in addition to a decrease in the carbon footprint
      of vehicles. The aforementioned positive environmental impact is further
      strengthened considering the lack of acute toxicity found in our extensive in
      vitro investigation, in which both eukaryotic and prokaryotic cells were tested.
      Collectively, our body of work suggests that by the use of safe nanoadditives we
      could contribute to reducing the environmental impact of transportation and
      therein take a positive step towards a more sustainable automotive sector. The
      workflow proposed here for the evaluation of human and environmental toxicity
      will allow for the study of nanosized bare graphene material and can be broadly
      applied to the translation of graphene-based nanomaterials into the market.

PMID- 29577121
TI  - Evaluation of the nutrition and function of cow and goat milk based on intestinal
      microbiota by metagenomic analysis.
AB  - Milk contains nutrients needed by the body, and the main components of different
      animal milk vary. Accordingly, we evaluated cow and goat milk's nutrition and
      their effects on the gut microbiota in mice models using a high-throughput 16S
      rRNA sequencing technology. The intestinal microbiota of mice changed
      significantly after the intake of cow and goat milk, and the goat milk had a
      greater effect on the intestinal microbial community than the cow milk.
      Bifidobacterium, Allobaculum, Olsenella and Akkermansia grew significantly in
      both cow and goat milk groups compared with the control group, indicating that
      milk positively affected their growth. We also found that the citrate cycle (TCA
      cycle), pyruvate metabolism, and amino sugar and nucleotide sugar metabolism, as
      well as lipoic acid metabolism, were higher in the goat milk group than in the
      cow milk group. Association analysis of milk components and their representative
      intestinal microbiota showed that casein, alphas1-casein, and beta + kappa-casein
      were positively correlated with Enterococcus and Allobaculum, and negatively
      correlated with Roseburia. Protein and alphas2-casein were positively associated
      with Akkermansia, Bifidobacterium and Eubacterium.

PMID- 29577122
TI  - CO oxidation activity of Pt, Zn and ZnPt nanocatalysts: a comparative study by in
      situ near-ambient pressure X-ray photoelectron spectroscopy.
AB  - The investigation of nanocatalysts under ambient pressure by X-ray photoelectron
      spectroscopy gives access to a wealth of information on their chemical state
      under reaction conditions. Considering the paradigmatic CO oxidation reaction, a
      strong synergistic effect on CO catalytic oxidation was recently observed on a
      partly dewetted ZnO(0001)/Pt(111) single crystal surface. In order to bridge the
      material gap, we have examined whether this inverse metal/oxide catalytic effect
      could be transposed on supported ZnPt nanocatalysts deposited on rutile
      TiO2(110). Synchrotron radiation near-ambient pressure X-ray photoelectron
      spectroscopy (NAP-XPS) operated at 1 mbar of O2 : CO mixture (4 : 1) was used at
      a temperature range between room temperature and 450 K. To tackle the complexity
      of the problem, we have also studied the catalytic activity of nanoparticles
      (NPs) of the same size, consisting of pure Pt and Zn nanoparticles (NPs), for
      which, moreover, NAP-XPS studies are a novelty. The comparative approach shows
      that the CO oxidation process is markedly different for the pure Pt and pure Zn
      NPs. For pure Pt NPs, CO poisoned the metallic surfaces at low temperature at the
      onset of CO2 evolution. In contrast, the pure Zn NPs first oxidize into ZnO, and
      trap carbonates at low temperature. Then they start to release CO2 in the gas
      phase, at a critical temperature, while continuously producing it. The pure Zn
      NPs are also immune to support encapsulation. The bimetallic nanoparticle borrows
      some of its characteristics from its two parent metals. In fact, the ZnPt NP,
      although produced by the sequential deposition of platinum and zinc, is platinum
      terminated below the temperature onset of CO oxidation and poisoned by CO. Above
      the CO oxidation onset, the nanoparticle becomes Zn-rich with a ZnO shell. Pure
      Pt and ZnPt NPs present a very similar activity towards CO oxidation, in contrast
      with what is reported in a single crystal study. The present study demonstrates
      the effectiveness of NAP-XPS in the study of complex catalytic processes at work
      on nanocatalysts under near-ambient pressures, and highlights once more the
      difficulty of transposing single crystal surface observations to the case of
      nanoobjects.

PMID- 29577123
TI  - Recent advances in functionalized micro and mesoporous carbon materials:
      synthesis and applications.
AB  - Functionalized nanoporous carbon materials have attracted the colossal interest
      of the materials science fraternity owing to their intriguing physical and
      chemical properties including a well-ordered porous structure, exemplary high
      specific surface areas, electronic and ionic conductivity, excellent
      accessibility to active sites, and enhanced mass transport and diffusion. These
      properties make them a special and unique choice for various applications in
      divergent fields such as energy storage batteries, supercapacitors, energy
      conversion fuel cells, adsorption/separation of bulky molecules, heterogeneous
      catalysts, catalyst supports, photocatalysis, carbon capture, gas storage,
      biomolecule detection, vapour sensing and drug delivery. Because of the
      anisotropic and synergistic effects arising from the heteroatom doping at the
      nanoscale, these novel materials show high potential especially in
      electrochemical applications such as batteries, supercapacitors and
      electrocatalysts for fuel cell applications and water electrolysis. In order to
      gain the optimal benefit, it is necessary to implement tailor made
      functionalities in the porous carbon surfaces as well as in the carbon skeleton
      through the comprehensive experimentation. These most appealing nanoporous carbon
      materials can be synthesized through the carbonization of high carbon containing
      molecular precursors by using soft or hard templating or non-templating pathways.
      This review encompasses the approaches and the wide range of methodologies that
      have been employed over the last five years in the preparation and
      functionalisation of nanoporous carbon materials via incorporation of metals, non
      metal heteroatoms, multiple heteroatoms, and various surface functional groups
      that mostly dictate their place in a wide range of practical applications.

PMID- 29577124
TI  - First characterization of a biphasic, switch-like DNA amplification.
AB  - We report the first DNA amplification chemistry with switch-like characteristics:
      the chemistry is biphasic, with an expected initial phase followed by an
      unprecedented high gain burst of product oligonucleotide in a second phase. The
      first and second phases are separated by a temporary plateau, with the second
      phase producing 10 to 100 times more product than the first. The reaction is
      initiated when an oligonucleotide binds and opens a palindromic looped DNA
      template with two binding domains. Upon loop opening, the oligonucleotide trigger
      is rapidly amplified through cyclic extension and nicking of the bound trigger.
      Loop opening and DNA association drive the amplification reaction, such that
      reaction acceleration in the second phase is correlated with DNA association
      thermodynamics. Without a palindromic sequence, the chemistry resembles the
      exponential amplification reaction (EXPAR). EXPAR terminates at the initial
      plateau, revealing a previously unknown phenomenon that causes early reaction
      cessation in this popular oligonucleotide amplification reaction. Here we present
      two distinct types of this biphasic reaction chemistry and propose dominant
      reaction pathways for each type based on thermodynamic arguments. These reactions
      create an endogenous switch-like output that reacts to approximately 1 pM
      oligonucleotide trigger. The chemistry is isothermal and can be adapted to
      respond to a broad range of input target molecules such as proteins, genomic
      bacterial DNA, viral DNA, and microRNA. This rapid DNA amplification reaction
      could potentially impact a variety of disciplines such as synthetic biology,
      biosensors, DNA computing, and clinical diagnostics.

PMID- 29577125
TI  - Biotin-functionalized targeted polydiacetylene micelles.
AB  - Polydiacetylene micelles were functionalized with controlled amounts of biotin
      using bioorthogonal click chemistry. The biotinylated micelles were evaluated in
      the selective targeting of the MCF-7 cancerous cell line and were shown to be
      readily internalized. The efficiency of the cellular uptake was correlated to the
      density of grafted biotin.

PMID- 29577126
TI  - Geminal cross-coupling synthesis, ion-induced emission and lysosome imaging of
      cationic tetraarylethene oligoelectrolytes.
AB  - Neutral conjugated tetraarylethenes OFn (n = 1-3) and the corresponding cationic
      conjugated oligoelectrolytes OFn+ (n = 1-3) with aggregation-induced emission
      activity have been designed and synthesized using geminal cross-coupling. OFn+ (n
      = 1-3) feature ion-induced emission in aqueous solution. They are used for
      lysosomal fluorescence imaging and tracing of lysosome events.

PMID- 29577127
TI  - White zein colloidal particles: synthesis and characterization of their optical
      properties on the single particle level and in concentrated suspensions.
AB  - Growing interest in using natural, biodegradable ingredients for food products
      leads to an increase in research for alternative sources of functional
      ingredients. One alternative is zein, a water-insoluble protein from corn. Here,
      a method to investigate the optical properties of white zein colloidal particles
      is presented in both diluted and concentrated suspensions. The particles are
      synthesized, after purification of zein, by anti-solvent precipitation. Mean
      particle diameters ranged from 35 to 135 nm based on dynamic light scattering.
      The value of these particles as white colorant is examined by measuring their
      optical properties. Dilute suspensions are prepared to measure the extinction
      cross section of individual particles and this was combined with Mie theory to
      determine a refractive index (RI) of 1.49 +/- 0.01 for zein particles dispersed
      in water. This value is used to further model the optical properties of
      concentrated suspensions. To obtain full opacity of the suspension, comparable to
      0.1-0.2 wt% suspensions of TiO2, concentrations of 2 to 3.3 wt% of zein particles
      are sufficient. The optimal size for maximal scattering efficiency is explored by
      modeling dilute and concentrated samples with RI's matching those of zein and
      TiO2 particles in water. The transport mean free path of light was determined
      experimentally and theoretically and the agreement between the transport mean
      free path calculated from the model and the measured value is better than 30%.
      Such particles have the potential to be an all-natural edible alternative for
      TiO2 as white colorant in wet food products.

PMID- 29577128
TI  - A high-response transparent heater based on a CuS nanosheet film with superior
      mechanical flexibility and chemical stability.
AB  - Transparent heaters are widely used in technologies such as window
      defrosting/defogging, displays, gas sensing, and medical equipment. Apart from
      mechanical robustness and electrical and optical reliabilities, outstanding
      chemical stability is also critical to the application of transparent heaters. In
      this regard, we first present a highly flexible and large-area CuS transparent
      heater fabricated by a colloidal crackle pattern method with an optimized sheet
      resistance (Rs) as low as 21.5 Omega sq-1 at a ~80% transmittance. The CuS
      transparent heater exhibits remarkable mechanical robustness during bending tests
      as well as high chemical stability against acid and alkali environments. In the
      application as a transparent heater, the CuS heater demonstrates a high thermal
      resistance of 197  degrees C W-1 cm2 with a fast switching time (<30 s),
      requiring low input voltages (<4.5 V) to achieve uniform temperatures of ~110 
      degrees C across large areas. The temperature of the wearable CuS heater, which
      is stuck on the skin, can be real-time controlled through a Bluetooth device in a
      cell phone wirelessly. Based on the wireless control system, we demonstrated an
      application of the CuS heater in snow removal for solar panels. These CuS network
      TCEs with high flexibility, transparency, conductivity, and chemical stability
      could be widely used in wearable electronic products.

PMID- 29577129
TI  - Chiral catalysts immobilized on achiral polymers: effect of the polymer support
      on the performance of the catalyst.
AB  - Positive effects of the polymeric support on the performance of supported chiral
      catalysts, in terms of activity, stability and selectivity-enantioselectivity,
      have been reported when the support is properly selected and optimized opening
      the way to the design of more efficient catalytic systems.

PMID- 29577130
TI  - Static and dynamic properties of a semiflexible polymer in a crowded environment
      with randomly distributed immobile nanoparticles.
AB  - Molecular dynamic simulations are performed for semiflexible polymers in a
      crowded environment with randomly distributed immobile nanoparticles (NPs).
      Herein, the effects of chain stiffness (ktheta), polymer-NP interaction
      (epsilonPN), and concentration of NPs (CNP) on the static and dynamic properties
      of the polymers have been studied. The mean square radius of gyration RG2 can be
      increased, decreased, or unchanged depending on these three variables. For a
      fully flexible polymer (ktheta = 0), RG2 changes non-monotonously with epsilonPN
      and CNP. However, for a semiflexible polymer (ktheta = 10 with its persistence
      length larger than the inter-particle distance of the NPs), RG2 decreases
      monotonously or remains unchanged with an increase in epsilonPN or CNP; this
      indicates the softening of polymer by the NPs. Moreover, the translational
      diffusion and rotation of the polymer are retarded by the NPs. Subdiffusion is
      observed for both the fully flexible polymer and semiflexible polymer at a
      sufficiently large epsilonPN. The effect of NPs on the translational diffusion is
      more obvious for the fully flexible polymer because more monomers are in contact
      with the NPs in the fully flexible polymer. In contrast, the effect of NPs on
      rotation is more obvious for the semiflexible polymer because it is in contact
      with more NPs. Furthermore, the rotational relaxation time tauR of the
      semiflexible polymer increases faster with an increase in epsilonPN or CNP than
      that of the fully flexible polymer.

PMID- 29577131
TI  - Bright monolayer tungsten disulfide via exciton and trion chemical modulations.
AB  - Atomically thin transition metal dichalcogenides (TMDCs) with exceptional
      electrical and optical properties have drawn tremendous attention for use in
      novel optoelectronic applications as photodetectors, transistors, light emitters,
      etc. However, electron bound trions formed through the combination of neutral
      excitons and electrons significantly decrease the photoluminescence (PL)
      efficiency of TMDCs. In this study, we report a simple yet efficient chemical
      doping strategy to modulate the optical properties of monolayer tungsten
      disulfide (WS2). As a demonstrative example, a chemically doped monolayer of WS2
      exhibits remarkable PL enhancement of about one order of magnitude higher than
      that of pristine WS2. This outstanding PL enhancement is attributed to the fact
      that excess electrons, which promote the formation of electron-bound trions, are
      reduced in number through charge transfer from WS2 to the chemical dopant.
      Furthermore, an improved degree of circular polarization from ~9.0% to ~41.5% was
      also observed in the chemically doped WS2 monolayer. This work describes a
      feasible strategy to manipulate the optical properties of TMDCs via exciton
      modulation, making TMDCs promising candidates for versatile semiconductor-based
      photonic devices.

PMID- 29577132
TI  - Full-color capable light-emitting diodes based on solution-processed quantum dot
      layer stacking.
AB  - To date, most of the studies on quantum dot-light-emitting diodes (QLEDs) have
      been dedicated to the fabrication of high-efficiency monochromatic devices.
      However, for the ultimate application of QLEDs to the next-generation display
      devices, QLEDs should possess a full-color emissivity. In this study, we report
      the fabrication of all-solution-processed full-color-capable white QLEDs with a
      standard device architecture, where sequentially stacked blue (B)/green (G)/red
      (R) quantum dot (QD)-emitting layers (EMLs) are sandwiched by poly(9
      vinylcarbazole) as the hole transport layer and ZnO nanoparticles (NPs) as the
      electron transport layer. To produce interlayer mixing-free, well-defined B/G/R
      QD layering assemblies via successive spin casting, an ultrathin ZnO NP buffer is
      inserted between different-colored QD layers. The present full-color-capable
      white QLED exhibits high device performance with the maximum values of 16 241 cd
      m-2 for luminance and 6.8% for external quantum efficiency. The promising results
      indicate that our novel EML design of ZnO NP buffer-mediated QD layer stacking
      may afford a viable means towards bright, efficient full-color-capable white
      devices.

PMID- 29577133
TI  - Cross dehydrogenative coupling of sugar enol ethers with terminal alkenes in the
      synthesis of pseudo-disaccharides, chiral oxadecalins and a conjugated triene.
AB  - An efficient strategy for the synthesis of C-2 and C-3 branched sugar dienes via
      cross dehydrogenative coupling of sugar enol ethers with terminal alkenes was
      developed. Both pyran and furan based enol ethers coupled smoothly with electron
      rich as well as deficient alkene sources yielding sugar dienes with complete E
      stereoselectivity. This coupling reaction was applied successfully for the
      synthesis of orthogonally protected pseudo-C-saccharides as an alternative to
      olefin metathesis. Substrate scope was further enhanced by reacting exoglycals
      with methyl acrylate to generate C-5 branched sugars with moderate
      diastereoselectivity. These diene subunits were reacted with maleic anhydride
      under [4 + 2] cycloaddition conditions to generate highly functionalised chiral
      oxadecalin cores. Finally, utilizing this C-C bond formation, a sugar based
      conjugated triene was synthesized in excellent yield and selectivity.

PMID- 29577134
TI  - Bis(phenylsulfonyl)methane mediated synthesis of olefins via a halogen
      elimination and double bond migration.
AB  - An effective dehydrochlorination of bis(phenylsulfonyl)alkane to prepare alkene
      building blocks is developed. The elimination together with double bond migration
      results in a variety of beta,gamma-unsaturated bis(phenylsulfonyl)olefins in good
      yields with only E geometry. The following chemical diversification represents an
      easy and straightforward access to a series of alkene building blocks.

PMID- 29577135
TI  - Metallic CuCo2S4 nanosheets of atomic thickness as efficient bifunctional
      electrocatalysts for portable, flexible Zn-air batteries.
AB  - Optimized catalysts show great potential for renewable energy storage and
      conversion. Herein, we report metallic CuCo2S4 nanosheets (NSs) of atomic
      thickness as efficient bifunctional electrocatalysts for use in portable,
      flexible Zn-air batteries. The metallic CuCo2S4 NSs of atomic thickness with 4
      atom-thick to 6-atom-thick layers are confirmed by temperature-dependent
      electrical resistance measurements and atomic force microscopy. Furthermore,
      extended X-ray absorption fine structure spectroscopy confirms that CuCo2S4 NSs
      with sulfur vacancies can further increase the OER activity. Due to high
      electrical conductivity and ultrathin nanosheet structure with abundant defects,
      CuCo2S4 NSs exhibit excellent reversible oxygen catalytic performance with an
      overpotential of 287 mV (at j = 10 mA cm-2) for the oxygen evolution reaction
      (OER) and an onset potential of 0.90 V for the oxygen reduction reaction (ORR).
      Additionally, the portable, flexible Zn-air battery using CuCo2S4 NSs as the air
      cathode displays a high open circuit voltage and strong rechargeable capacity for
      18 h. The present study highlights the importance of designing metallic catalysts
      having atomic thickness with surface defects for highly efficient and stable
      renewable energy storage and conversion.

PMID- 29577136
TI  - The adsorption of helium atoms on small cationic gold clusters.
AB  - Adducts formed between small gold cluster cations and helium atoms are reported
      for the first time. These binary ions, Aun+Hem, were produced by electron
      ionization of helium nanodroplets doped with neutral gold clusters and were
      detected using mass spectrometry. For a given value of n, the distribution of
      ions as a function of the number of added helium atoms, m, has been recorded.
      Peaks with anomalously high intensities, corresponding to so-called magic number
      ions, are identified and interpreted in terms of the geometric structures of the
      underlying Aun+ ions. These features can be accounted for by planar structures
      for Aun+ ions with n <= 7, with the addition of helium having no significant
      effect on the structures of the underlying gold cluster ions. According to ion
      mobility studies and some theoretical predictions, a 3-D structure is expected
      for Au8+. However, the findings for Au8+ in this work are more consistent with a
      planar structure.

PMID- 29577137
TI  - C5-Morpholinomethylation of N1-sulfonylcytosines by a one-pot microwave assisted
      Mannich reaction.
AB  - A fast and efficient route for the introduction of a methylene bridged-amine
      (morpholinomethyl) functionality in the C5 position of the sulfonylated cytosine
      nucleobase has been developed. First, novel N1-sulfonylcytosine derivatives 3-6
      were prepared by the condensation of silylated cytosine with selected sulfonyl
      chlorides. They were subsequently transformed to 5-morpholinomethyl-N1
      sulfonylcytosine derivatives (8, 12-15) using microwave irradiation. As a result
      of cytosine ring opening in N1-tosylcytosine, depending on the reaction
      conditions, peculiar tosyl-urea derivative 9 has been isolated, which provided
      additional insight into the reaction pathway. The influence of the C5-substituent
      on the antiproliferative activity has been evaluated by performing the MTT test
      on U251, MCF-7 and MOLT-4 tumor cell-lines.

PMID- 29577138
TI  - The modeling of the absorption lineshape for embedded molecules through a
      polarizable QM/MM approach.
AB  - We present a computational strategy to simulate the absorption lineshape of a
      molecule embedded in a complex environment by using a polarizable QM/MM approach.
      This strategy is presented in two alternative formulations, one based on a
      molecular dynamics simulation of the structural fluctuations of the system and
      the other using normal modes and harmonic frequencies calculated on optimized
      geometries. The comparison for the case of a chromophore within a strongly
      inhomogeneous and structured environment, namely the intercalation pocket of DNA,
      shows that the MD-based approach is able to reproduce the experimental spectral
      bandshape. In contrast, the static approach overestimates the vibronic coupling,
      resulting in a much broader band.

PMID- 29577139
TI  - Improving Luttinger-liquid plasmons in carbon nanotubes by chemical doping.
AB  - We realized the real-space imaging of Luttinger-liquid plasmons in semiconducting
      single-walled carbon nanotubes (s-SWCNTs) and studied the effects of chemical
      doping-induced charge carrier density modulation on plasmons. Using scattering
      type scanning near-field optical microscopy (s-SNOM), we compared the Luttinger
      liquid plasmonic behavior in pre- and post-HNO3-doped SWCNTs. Raman measurements
      revealed that the physical mechanism is P-type doping. Through HNO3 doping, we
      effectively increased the charge carrier density in s-SWCNTs and achieved quantum
      plasmons simultaneously with strong confinement (lambda0/lambdap ~ 70) and high
      quality factor (Q ~ 20). The combination of high quality factor and strong
      subwavelength confinement in Luttinger-liquid plasmons is critical to the future
      application of plasmonic devices.

PMID- 29577140
TI  - Bilayers of Janus and homogeneous particle mixtures trapped at an air/water
      interface.
AB  - We study mixtures of amphiphilic Janus and homogeneous hydrophobic particles
      trapped at an air/water interface. In contrast to an expected monolayer
      formation, bilayers of colloidal particles are produced. Despite their strong
      interfacial adsorption, Janus particles form the upper layer. They are not placed
      on top of the other particles but rather shifted about one-third of the particle
      diameter. To understand the mechanism of bilayer formation, particle behaviour at
      the surface and in the bulk of the spreading solvent is considered. The vertical
      shift and the bilayer formation are assisted by the momentous formation of two
      interfaces during spreading.

PMID- 29577141
TI  - The heat capacities and critical behaviors of binary ionic solutions.
AB  - The heat capacities of nine binary room temperature ionic solutions {[C4mim][BF4]
      + 1,2-butandiol}, {[C8mim][BF4] + 1-pentanol}, {[C8mim][BF4] + 2-pentanol},
      {[C8mim][BF4] + 1-hexanol}, {[C8mim][BF4] + 1-heptanol}, {[C8mim][PF6] + 1
      propanol}, {[C8mim][PF6] + 1-butanol}, {[C8mim][PF6] + 2-butanol} and
      {[C8mim][PF6] + tert-butanol} are reported herein. The combination of the data
      obtained with the corresponding measured coexistence curves infers that the
      critical asymmetry parameter of the coexistence curves linearly varies with the
      molar volume ratio of the two components for each of the studied binary ionic
      solutions after the heat capacity contribution is considered. This indicates the
      importance of the heat capacity contribution to the critical asymmetry. For
      further analysis of the critical characteristics of the ionic solutions, a large
      amount of experimental data was collected and systematically discussed in detail
      regarding which critical character is important in the binary ionic solutions. A
      general increasing tendency for the RPM (restricted primitive model)-rescaled
      critical parameters with the relative permittivity epsilonr,c of the solvent at
      the critical temperature of the corresponding system was found. This is
      attributed not only to the screening effect of the solvent medium, but also to
      solvophobic interactions, which both increase with epsilonr,c. This study also
      demonstrates that the critical amplitudes increased, while the relative
      contribution of the heat capacity to the asymmetry of the coexistence curve
      decreased with an increase in epsilonr,c.

PMID- 29577142
TI  - X-Ray diffraction and resonance shear measurement of nano-confined ionic liquids.
AB  - X-ray diffraction measurement at the SPring-8 synchrotron was employed to
      investigate the structures of two types of imidazolium-based ionic liquids (ILs),
      1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C4mim][NTF2])
      and 1-butyl-3-methylimidazolium tetrafluoroborate ([C4mim][BF4]), confined
      between silica surfaces by varying the surface separation distances of ca. 500 nm
      (bulk liquid), ca. 10 nm, and ca. 2 nm (hard wall thickness). The obtained
      diffraction profiles and intensities were discussed by considering the structures
      and properties of the nano-confined ILs between the silica surfaces investigated
      by resonance shear measurement (RSM) and molecular dynamics simulation (MD) in
      our previous reports. [C4mim][NTf2] showed two diffraction peaks at q = 8.8 nm-1
      (spacing d = 0.71 nm) and at q = 14.0 nm-1 (spacing d = 0.45 nm) at the greatest
      distance (D = ca. 500 nm), which were assigned to the interval between the same
      ions (anion-anion or cation-cation) within the polar network of [C4mim][NTf2] and
      the interval between the neighboring anion-cation, respectively. The positions of
      these two peaks remained the same at D = ca. 10 nm and at the hard wall (D = ca.
      2 nm) and their intensity factor increased, indicating that both the cation and
      anion existed in the same layer. This result was consistent with the checkerboard
      structure of [C4mim][NTf2] on the silica surface computer simulated in our
      previous studies. On the other hand, [C4mim][BF4] showed a peak at q = 15.4 nm-1
      (spacing d = 0.41 nm) corresponding to the anion-cation interval at the greatest
      distance (D = ca. 500 nm). This peak became broader and weaker at D = ca. 12 nm
      and at D = ca. 2 nm.

PMID- 29577143
TI  - The art in science of MicroTAS: 10 years of miniaturized art.

PMID- 29577144
TI  - Scan-rate and vacuum pressure dependence of the nucleation and growth dynamics in
      a spin-crossover single crystal: the role of latent heat.
AB  - Using optical microscopy we studied the vacuum pressure dependence (0.1-1000
      mbar) of the nucleation and growth dynamics of the thermally induced first-order
      spin transition in a single crystal of the spin-crossover compound [Fe(HB(tz)3)2]
      (tz = 1,2,4-triazol-1-yl). A crossover between a quasi-static hysteresis regime
      and a temperature-scan-rate-dependent kinetic regime is evidenced around 5 mbar
      due to the change of the heat exchange coupling between the crystal and its
      external environment. Remarkably, the absorption/dissipation rate of latent heat
      was identified as the key factor limiting the switching speed of the crystal.

PMID- 29577145
TI  - Dual effects of water vapor on ceria-supported gold clusters.
AB  - Atomically precise nanocatalysts are currently being intensely pursued in
      catalysis research. Such nanocatalysts can serve as model catalysts for gaining
      fundamental insights into catalytic processes. In this work we report a discovery
      that water vapor provokes the mild removal of surface long-chain ligands on 25
      atom Au25(SC12H25)18 nanoclusters in a controlled manner. Using the resultant
      Au25(SC12H25)18-x/CeO2 catalyst and CO oxidation as a probe reaction, we found
      that the catalytic activity of cluster/CeO2 is enhanced from nearly zero
      conversion of CO (in the absence of water) to 96.2% (in the presence of 2.3 vol%
      H2O) at the same temperature (100  degrees C). The cluster catalysts exhibit high
      stability during the CO oxidation process under moisture conditions (up to 20
      vol% water vapor). Water vapor plays a dual role in gold cluster-catalyzed CO
      oxidation. FT-IR and XPS analyses in combination with density functional theory
      (DFT) simulations suggest that the "-SC12H25" ligands are easier to be removed
      under a water vapor atmosphere, thus generating highly active sites. Moreover,
      the O22- peroxide species constitutes the active oxygen species in CO oxidation,
      evidenced by Raman spectroscopy analysis and isotope experiments on the CeO2 and
      cluster/CeO2. The results also indicate the perimeter sites of the interface of
      Au25(SC12H25)18-x/CeO2 to be active sites for catalytic CO oxidation. The
      controlled exposure of active sites under mild conditions is of critical
      importance for the utilization of clusters in catalysis.

PMID- 29577146
TI  - Nitrogen self-doped carbon aerogels derived from trifunctional benzoxazine
      monomers as ultralight supercapacitor electrodes.
AB  - Ultralight benzoxazine-derived porous nitrogen self-doped carbon aerogels with
      good yield can be prepared by direct polymerization of trifunctional benzoxazine
      monomers under acid catalysis using concentrated hydrochloric acid. This allows
      for a significantly widened density range (0.8-4.5 mg cm-3) and avoids any
      sacrificial etching. When serving as electrode materials for supercapacitors, the
      resulting hierarchical porous carbon aerogels show ultrahigh specific
      capacitance, excellent rate performance and good cycling stability (retention of
      97.3% even after 10 000 continuous charge-discharge cycles). Besides energy
      storage devices, the interconnected nanoporous carbon aerogels can also find
      applications in oil/water separation, heavy metal removal, catalyst supports, and
      so forth.

PMID- 29577147
TI  - Functional and stability orientation synthesis of materials and structures in
      aprotic Li-O2 batteries.
AB  - The lithium-O2 battery is one of most promising energy storage and conversion
      devices due to its ultrahigh theoretical energy density and hence has broad
      application potential in electrical vehicles and stationary power systems.
      However, the present Li-O2 battery suffers from a series of challenges for its
      practical application, such as its low capacity and rate capability, poor round
      trip efficiency and short cycle life. These challenges mainly arise from the
      sluggish and unsustainable discharge and charge reactions at lithium and oxygen
      electrodes, which determine the performance and durability of a battery. In this
      review, we first provide insights on the present understanding of the
      discharge/charge mechanism of such a battery and follow up with establishing a
      correlation between the specific materials/structures of the battery modules and
      their functionality/stability within the recent progress in electrodes,
      electrolytes and redox mediators. Considerable emphasis is paid to the importance
      of functional orientation design and the synthesis of materials/structures
      towards accelerating and sustaining the electrode reactions of Li-O2 batteries.
      Moreover, the future directions and perspectives of rationally constructed
      material and surface/interface structures, as well as their optimal combinations
      are proposed for enhancement of the electrode reaction rate and sustainability,
      and consequently for a better performance and durability of such batteries.

PMID- 29577148
TI  - In situ simultaneous profiling of phosphorylation and ubiquitination by single
      excitation-duplexed luminescence resonance energy transfer.
AB  - A dual luminescence resonance energy transfer system is developed based on
      aptamer-functionalized upconversion nanoparticles as the energy donor and a
      synthetic dye derivative as the acceptor, which can be applied in the
      simultaneous profiling and relative quantification of phosphorylation and
      ubiquitination on a specific protein, even at low levels of protein expression.

PMID- 29577149
TI  - Sulfur-driven switching of the Ullmann coupling on Au(111).
AB  - We demonstrate a method to selectively switch the Ullmann coupling reaction of
      2,8-dibromodibenzothiophene on a Au(111) support. The Ullmann coupling reaction
      is effective already at low temperature, but the complete inhibition of the same
      reaction can be achieved on Au(111) pre-exposed to H2S. The marked difference in
      reactivity of pretreated Au(111) is explained by the S-passivation of free Au
      atoms emerging from reconstruction sites. The inhibited state can be fully lifted
      by removing the S via hydrogen gas post-exposure.

PMID- 29577150
TI  - Synthesis and optical properties of ordered-vacancy perovskite cesium bismuth
      halide nanocrystals.
AB  - Perovskite-phase cesium bismuth halide (Cs3Bi2X9; X = Cl, Br, I) nanocrystals
      were synthesized using a hot-injection approach. These nanocrystals adopted
      ordered-vacancy perovskite crystal structures and demonstrated composition
      tunable optical properties. Growth occurred by initial formation of Bi0 seeds,
      and morphology was controlled by precursor and seed concentration. The Cs3Bi2I9
      nanocrystals demonstrated excellent stability under ambient conditions for
      several months. Contrary to previous reports, we find that photoluminescence
      originates from the precursor material as opposed to the Cs3Bi2X9 nanocrystals.

PMID- 29577151
TI  - A highly sensitive and selective fluorescent probe for fast sensing of endogenous
      HClO in living cells.
AB  - A new fluorescence probe was developed for HClO detection under physiological
      conditions, which displayed fast response (t1/2 < 30 s) and large off-on
      fluorescence increase (>1000-fold) toward HClO with high sensitivity and
      selectivity. The probe was successfully applied for the detection of both
      exogenous and endogenous HClO in living cells. Using the probe-based tool, we
      could observe the H2S-induced HClO biogenesis in living cells for the first time.

PMID- 29577152
TI  - Zipping and unzipping monolayers: switchable monolayer oligomerization and
      adhesion via thiol-disulfide interconversion.
AB  - Triphenyleneethynylene (TPE) monolayers at the solution-HOPG interface are
      oligomerized by the oxidation of pendant thioethers to form disulfide cross
      links. The oligomerized TPE monolayer adheres strongly to HOPG. Disulfide
      reduction unzips the oligomers to form a monomeric TPE monolayer with pendant
      thiols. Subsequent oxidation and reduction treatments zip and unzip the
      monolayer.

PMID- 29577153
TI  - Time dependence of NMR observables reveals salient differences in the
      accumulation of early aggregated species between human islet amyloid polypeptide
      and amyloid-beta.
AB  - Type 2 diabetes mellitus and Alzheimer's disease are characterized by the
      accumulation of fibrillar amyloid deposits consisting mainly of islet amyloid
      polypeptide (IAPP) and amyloid-beta (Abeta), respectively. Fibril formation is a
      multi-step nucleation process that involves the transient build-up of oligomeric
      species that are thought to be the most toxic components. To gain more insight
      into the molecular mechanism of early IAPP aggregated species formation, we
      performed a combination of direct and indirect biophysical approaches on IAPP and
      also on Abeta42 for the sake of comparison. Thioflavin T fluorescence kinetics
      measurements revealed a stronger autocatalytic behaviour of IAPP and a weaker
      concentration dependence of fibrillization half-time t1/2, as compared to
      Abeta42. Our NMR experiments highlight the absence of micelle reservoir or
      supercritical regime in the studied concentration range, indicating that the low
      concentration dependence of IAPP fibril formation can be ascribed to saturable
      pathways. IAPP and Abeta42 displayed marked differences in formation of
      oligomeric species, as observed by 1D 1H, pulsed-field gradient (PFG) diffusion
      and saturation transfer difference (STD) NMR experiments. A fast equilibrium
      between monomer and oligomeric species was detected in the case of Abeta42 but
      not IAPP, with a significant build-up of aggregated species, as shown by the time
      dependence of diffusion coefficient and STD magnetization transfer efficiency
      during the aggregation process. Altogether our data show significant differences
      between IAPP and Abeta42 regarding the microscopic events of amyloid species
      formation.

PMID- 29577154
TI  - Noninvasive and prospective diagnosis of coronary heart disease with urine using
      surface-enhanced Raman spectroscopy.
AB  - A prospective diagnosis method for coronary heart disease (CHD) using human urine
      based on surface-enhanced Raman spectroscopy (SERS) is proposed, and could
      provide valuable information for judging whether to perform percutaneous coronary
      intervention (PCI) in clinics. Here, urine samples from 87 patients with CHD,
      including patients with PCI before operation (degree of cardiovascular congestion
      above 70%) and without PCI (degree of cardiovascular congestion under 70%), and
      20 healthy humans were measured using SERS. Principal component analysis (PCA)
      combined with linear discriminant analysis (LDA) was employed to analyze the SERS
      spectra, revealing that the classification sensitivity and specificity were 90%
      and 78.9%, respectively, and the absolute value for loading of PC1 at 1509 cm-1
      was the largest. Since platelet-derived growth factor-BB (PDGF-BB) is closely
      related to CHD, PDGF-BB aqueous solutions with various concentrations (1, 0.5,
      0.1, 0.05 and 0.01 ppm) and a mixture of healthy human urine and PDGF-BB aqueous
      solutions were then investigated in this work, and it was found that the Raman
      peak at 1509 cm-1 may be attributed to PDGF-BB. Moreover, the measured SERS
      spectra of all the urine samples from the 87 patients with CHD were compared with
      the clinical data provided by a hospital, and it was revealed that the appearance
      of a peak at 1509 cm-1 in the SERS spectra was in good agreement with the results
      of coronary angiography tests when cardiovascular congestion was above 70%. This
      indicated that the classification sensitivity and specificity were 87.9% and
      87.0%, respectively, through identification of the Raman peak at 1509 cm-1.

PMID- 29577155
TI  - Synthesis of spiroindolenines by intramolecular ipso-iodocyclization of indol
      ynones.
AB  - A high-yielding fast spirocyclization of easily available indol ynones has been
      developed by applying N-iodosuccinimide. The formation of the desired product
      occurs in an atom-economical way, under mild conditions, instantly after the
      addition of the reagent. The expected 1,2-rearrangement was not observed. The
      procedure represents a metal free spirocyclization of indoles with an opportunity
      for further functionalizations.

PMID- 29577156
TI  - The influence of manganese concentration on the sensitivity of bandshape and
      lifetime luminescent thermometers based on Y3Al5O12:Mn3+,Mn4+,Nd3+ nanocrystals.
AB  - Luminescent thermometers based on transition metal and lanthanide ion codoped
      nanocrystals have become a group of non-contact thermometers which are gaining
      importance due to their high sensitivity upon temperature changes. Here we
      present two types of luminescent thermometers, namely, bandshape and lifetime
      temperature sensors based on Y3Al5O12:Mn3+,Mn4+,Nd3+ nanocrystals. Their ability
      for temperature sensing was investigated as a function of Mn concentration. It
      was found that both sensitivity and usable temperature range depend on the Mn
      concentration. The highest sensitivity (S = 2.69%/K) was found for the lifetime
      luminescent thermometer with 0.01%Mn concentration and its value is gradually
      reduced with Mn content. Similarly, in the case of the bandshape luminescent
      thermometer, the sensitivity decreases from 1.69%/K for 0.01%Mn to 0.54%/K for
      1%Mn. On the other hand the usable temperature range extends with dopant
      concentration. The concentration effect on the temperature dependent optical
      parameters is discussed in terms of interionic interactions facilitated for
      shorter Mn-Mn distances.

PMID- 29577157
TI  - 2D carbon sheets with negative Gaussian curvature assembled from pentagonal
      carbon nanoflakes.
AB  - Despite the good progress made in materials fabrication, it remains a big
      challenge to synthesize 2D sheets by assembling nanoflakes that are usually
      produced in experiments, and few theoretical studies have explored this topic.
      Based on the recent experimental synthesis of pentagonal graphene nanoflakes and
      the novel properties of penta-graphene, we report a series of 2D assembled carbon
      allotropes (CG568-80, CG568-180 and CG568-320) that have the following unusual
      properties: different from most other 2D carbon allotropes, the assembled carbon
      sheets have negative Gaussian curvatures, and exhibit ultra-softness and better
      chemical reactivity due to the curvature-induced misalignment of pi-orbitals as
      compared with pristine graphene; all three studied carbon sheets are highly
      stable with binding energies comparable to those of phagraphene and psi-graphene,
      and are semiconductors with tunable band gaps, displaying size-dependent carrier
      mobilities: ~105 cm2 V-1 s-1 (CG568-80 and CG568-320) and ~104 cm2 V-1 s-1 (CG568
      180). These features indicate that assembling nanoflakes can effectively tune the
      structural morphology and properties to expand the family of 2D carbon materials
      for future applications.

PMID- 29577158
TI  - Determination of accurate backbone chemical shift tensors in microcrystalline
      proteins by integrating MAS NMR and QM/MM.
AB  - Chemical shifts are highly sensitive probes of local conformation and overall
      structure. Both isotropic shifts and chemical shift tensors are readily
      accessible from NMR experiments but their quantum mechanical calculations remain
      challenging. In this work, we report and compare accurately measured and
      calculated 15NH and 13Calpha chemical shift tensors in proteins, using the
      microcrystalline agglutinin from Oscillatoria agardhii (OAA). Experimental
      13Calpha and 15NH chemical tensors were obtained by solid-state NMR spectroscopy,
      employing tailored recoupling sequences, and for their quantum
      mechanics/molecular mechanics (QM/MM) calculations different sets of functionals
      were evaluated. We show that 13Calpha chemical shift tensors are primarily
      determined by backbone dihedral angles and dynamics, while 15NH tensors mainly
      depend on local electrostatic contributions from solvation and hydrogen bonding.
      In addition, the influence of including crystallographic waters, the molecular
      mechanics geometry optimization protocol, and the level of theory on the accuracy
      of the calculated chemical shift tensors is discussed. Specifically, the power of
      QM/MM calculations in accurately predicting the unusually upfield shifted 1HN G26
      and G93 resonances is highlighted. Our integrated approach is expected to benefit
      structure refinement of proteins and protein assemblies.

PMID- 29577159
TI  - Programed dynamical ordering in self-organization processes of a nanocube: a
      molecular dynamics study.
AB  - Self-organization processes of a gear-shaped amphiphile molecule (1) to form a
      hexameric structure (nanocube, 16) were inferred from sequential dissociation
      processes by using molecular dynamics (MD) simulations. Our MD study unveiled
      that programed dynamic ordering exists in the dissociation processes of 16.
      According to the dissociation processes, it is proposed that triple pi-stacking
      among three 3-pyridyl groups and other weak molecular interactions such as CH-pi
      and van der Waals interactions, some of which arise from the solvophobic effect,
      were sequentially formed in stable and transient oligomeric states in the self
      organization processes, i.e.12, 13, 14, and 15. By subsequent analyses on
      structural stabilities, it was found that 13 and 14 are stable intermediate
      oligomers, whereas 12 and 15 are transient ones. Thus, the formation of 13 from
      three monomers and of 16 from 14 and two monomers via corresponding transients is
      time consuming in the self-assembly process.

PMID- 29577160
TI  - Control of the rectifying effect and direction by redox asymmetry in Rh2-based
      molecular diodes.
AB  - Four asymmetrical self-assembled monolayers (SAMs) consisting of two subunits
      with different Rh2 building blocks present a pronounced rectifying behavior. The
      rectification ratio (RR) increases on increasing the redox potential difference
      between the two Rh2 subunits, and the rectifying direction can be reversed by
      reordering the subunits in the assembly.

PMID- 29577161
TI  - The active role of Ca2+ ions in Abeta-mediated membrane damage.
AB  - Calcium dysregulation, membrane leakage and Abeta amyloid growth are hallmarks of
      Alzheimer's disease. Here we show that Ca2+ ions inhibit membrane damage due to
      amyloid channels but enhance membrane disruption associated with fibers growing
      on the lipid surface. The similarities with IAPP suggest that this may represent
      a mechanism common to all proteinopathies.

PMID- 29577162
TI  - Bronsted acid-catalyzed formal [5+2+1] cycloaddition of ynamides and isoxazoles
      with water: access to oxygen-bridged tetrahydro-1,4-oxazepines.
AB  - A Bronsted acid-catalyzed formal [5+2+1] cycloaddition of ynamides and isoxazoles
      with water is described. This process provides atom-economical access to oxygen
      bridged tetrahydro-1,4-oxazepines, where the bridged oxygen atom originates from
      water. The unique property of the Bronsted acid shows distinct chemoselectivity
      from the corresponding gold-catalyzed cycloadditions.

PMID- 29577163
TI  - Gene microarray analysis of lncRNA and mRNA expression profiles in patients with
      high-grade ovarian serous cancer.
AB  - High-grade ovarian serous cancer is known for its high rates of invasion and
      metastasis, and resultant high mortality rate. Therefore, research concerning
      biomarkers and underlying molecular mechanisms of high-grade ovarian serous
      cancer progression and prognosis are urgently required. Long non-coding RNAs
      (lncRNAs) have been the subject of an increasing number of studies, and certain
      lncRNAs have been demonstrated to serve an important function in the development
      and progression of various cancers, including HOX transcript antisense RNA,
      competing endogenous lncRNA 2 for microRNA let-7b, urothelial cancer associated
      1, and H19, imprinted maternally expressed transcript (non-protein coding).
      However, few studies have investigated the differential expression of lncRNAs in
      high-grade ovarian serous cancer. In the present study, differences in lncRNA and
      mRNA expression profiles between high-grade ovarian serous cancer tissue samples
      and healthy fallopian tube tissue samples were investigated using microarray
      analysis, and the differential expression of lncRNAs and mRNAs was confirmed by
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then,
      five abnormally expressed lncRNAs were selected, and the associations between
      these lncRNAs and ovarian cancer clinicopathological parameters were examined
      using RT-qPCR. The expression profiles of certain lncRNAs and mRNAs were
      confirmed to be altered between high-grade ovarian serous cancer tissues and
      healthy fallopian tube tissues. Furthermore, the expression levels of selected
      lncRNAs were associated with International Federation of Gynecology and
      Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore
      be involved in the pathogenesis of high-grade ovarian serous cancer. The results
      of the present study provide an experimental foundation for further exploration
      of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of
      high-grade ovarian serous cancer.

PMID- 29577164
TI  - Assessment of CTNNB1 gene mutations and beta-catenin immunoexpression in salivary
      gland pleomorphic adenomas and adenoid cystic carcinomas.
AB  - beta-Catenin exerts multiple functions in several neoplasms, playing a major role
      in cell signaling and tumor progression. This study analyzed possible CTNNB1
      mutations in salivary gland pleomorphic adenomas (PAs) and adenoid cystic
      carcinomas (ACCs), and determined possible differences in beta-catenin
      immunoexpression in relation to these mutations, as well as histopathological
      aspects of these tumors. Twenty-four PAs (15 cell-rich and 9 cell-poor tumors)
      and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the
      analysis of beta-catenin distribution and cellular localization. Furthermore,
      beta-catenin expression was evaluated using the H-score scoring system. Mutations
      in CTNNB1 exon 3 were investigated by the single-strand conformational
      polymorphism test. Diffuse beta-catenin expression was more frequently observed
      in ACCs compared to PAs (P = 0.008). No significant difference in beta-catenin
      cellular localization was observed between these tumors (P = 0.098). Comparisons
      between PA and ACC cases revealed a higher median H-score in the latter (P =
      0.036). Cell-rich PAs exhibited a trend for higher H-score than cell-poor tumors
      (P = 0.060), whereas lower H-scores were observed in cribriform ACCs when
      compared to tubular and solid ACCs (P = 0.042). Mutations in CTNNB1 were observed
      in 6 PAs and 7 ACCs, with no significant difference in H-scores for beta-catenin
      according to mutation status (P = 0.135). beta-Catenin is important in the
      pathogenesis of salivary gland PAs and ACCs. In addition, CTNNB1 exon 3 mutations
      do not seem to significantly influence beta-catenin cytoplasmic/membranous
      expression or nuclear translocation in these tumors.

PMID- 29577167
TI  - Recent research on the physiological functions, applications, and
      biotechnological production of D-allose.
AB  - D-Allose is a rare monosaccharide, which rarely appears in the natural
      environment. D-Allose has an 80% sweetness relative to table sugar but is ultra
      low calorie and non-toxic and is thus an ideal candidate to take the place of
      table sugar in food products. It displays unique health benefits and
      physiological functions in various fields, including food systems, clinical
      treatment, and the health care fields. However, it is difficult to produce
      chemically. The biotechnological production of D-allose has become a research
      hotspot in recent years. Therefore, an overview of recent studies on the
      physiological functions, applications, and biotechnological production of D
      allose is presented. In this review, the physiological functions of D-allose are
      introduced in detail. In addition, the different types of D-allose-producing
      enzymes are compared for their enzymatic properties and for the biotechnological
      production of D-allose. To date, very little information is available on the
      molecular modification and food-grade expression of D-allose-producing enzymes,
      representing a very large research space yet to be explored.

PMID- 29577168
TI  - Spatial factors of white-tailed deer herbivory assessment in the central
      Appalachian Mountains.
AB  - Because moderate to over-abundant white-tailed deer (Odocoileus virginianus)
      herbivory impacts biodiversity and can alter community function, ecological
      benchmarks of herbivory impact are needed to assess deer impacts. We evaluated
      spatial patterns of deer herbivory and their relation to herbivory assessment by
      evaluating woody vegetation along 20 transects at each of 30 sites spread across
      a wide range of deer herd densities and vegetative condition throughout the
      biodiverse Appalachian Mountains of Virginia, USA. Surprisingly, herbivory
      patterns and the availability of woody forage generally were unchanged among
      physiographic regions and land use diversity classes. However, some relationships
      between browsing pattern and vegetation varied with scale. The total quantity of
      vegetation browsed on a given site and at the transect scale were related
      positively to the availability of forage, as the proportion of stems browsed
      decreased as stem density increased. However, this was only true when all stems
      were considered equally. When stem densities by species were weighted for deer
      preference, the proportion of stems browsed had no relationship or increased with
      stem density. Compared to the value from all transects sampled, on average, the
      mean of >= 3 transects within a site was within 0.1 of the browsing ratio and
      stem densities were within 0.5 stems m-2. Our results suggest that one transect
      per square kilometer with a minimum of three transects may be sufficient for most
      browsing intensity survey requirements to assess herbivory impacts in the
      Appalachian region of Virginia. Still, inclusion of spatial factors to help
      partition variation of deer herbivory potentially may allow for improved
      precision and accuracy in the design of field herbivory impact assessment methods
      and improve their application across various landscape contexts.

PMID- 29577166
TI  - An international Urogynecological association (IUGA)/international continence
      society (ICS) joint report on the terminology for the assessment of sexual health
      of women with pelvic floor dysfunction.
AB  - INTRODUCTION AND HYPOTHESIS: The terminology in current use for sexual function
      and dysfunction in women with pelvic floor disorders lacks uniformity, which
      leads to uncertainty, confusion, and unintended ambiguity. The terminology for
      the sexual health of women with pelvic floor dysfunction needs to be collated in
      a clinically-based consensus report. METHODS: This report combines the input of
      members of the Standardization and Terminology Committees of two International
      Organizations, the International Urogynecological Association (IUGA), and the
      International Continence Society (ICS), assisted at intervals by many external
      referees. Internal and external review was developed to exhaustively examine each
      definition, with decision-making by collective opinion (consensus). Importantly,
      this report is not meant to replace, but rather complement current terminology
      used in other fields for female sexual health and to clarify terms specific to
      women with pelvic floor dysfunction. RESULTS: A clinically based terminology
      report for sexual health in women with pelvic floor dysfunction encompassing over
      100 separate definitions, has been developed. Key aims have been to make the
      terminology interpretable by practitioners, trainees, and researchers in female
      pelvic floor dysfunction. Interval review (5-10 years) is anticipated to keep the
      document updated and as widely acceptable as possible. CONCLUSIONS: A consensus
      based terminology report for female sexual health in women with pelvic floor
      dysfunction has been produced aimed at being a significant aid to clinical
      practice and a stimulus for research.

PMID- 29577169
TI  - Classification of Alzheimer's Disease Based on Eight-Layer Convolutional Neural
      Network with Leaky Rectified Linear Unit and Max Pooling.
AB  - Alzheimer's disease (AD) is a progressive brain disease. The goal of this study
      is to provide a new computer-vision based technique to detect it in an efficient
      way. The brain-imaging data of 98 AD patients and 98 healthy controls was
      collected using data augmentation method. Then, convolutional neural network
      (CNN) was used, CNN is the most successful tool in deep learning. An 8-layer CNN
      was created with optimal structure obtained by experiences. Three activation
      functions (AFs): sigmoid, rectified linear unit (ReLU), and leaky ReLU. The three
      pooling-functions were also tested: average pooling, max pooling, and stochastic
      pooling. The numerical experiments demonstrated that leaky ReLU and max pooling
      gave the greatest result in terms of performance. It achieved a sensitivity of
      97.96%, a specificity of 97.35%, and an accuracy of 97.65%, respectively. In
      addition, the proposed approach was compared with eight state-of-the-art
      approaches. The method increased the classification accuracy by approximately 5%
      compared to state-of-the-art methods.

PMID- 29577170
TI  - Robotic rectal cancer surgery in obese patients may lead to better short-term
      outcomes when compared to laparoscopy: a comparative propensity scored match
      study.
AB  - PURPOSE: Laparoscopic rectal surgery in obese patients is technically
      challenging. The technological advantages of robotic instruments can help
      overcome some of those challenges, but whether this translates to superior short
      term outcomes is largely unknown. The aim of this study is to compare the short
      term surgical outcomes of obese (BMI >= 30) robotic and laparoscopic rectal
      cancer surgery patients. METHODS: All consecutive obese patients receiving
      laparoscopic and robotic rectal cancer resection surgery from three centres, two
      from the UK and one from Portugal, between 2006 and 2017 were identified from
      prospectively collated databases. Robotic surgery patients were propensity score
      matched with laparoscopic patients for ASA grade, neoadjuvant radiotherapy and
      pathological T stage. Their short-term outcomes were examined. RESULTS: A total
      of 222 patients were identified (63 robotic, 159 laparoscopic). The 63 patients
      who received robotic surgery were matched with 61 laparoscopic patients. Cohort
      characteristics were similar between the two groups. In the robotic group,
      operative time was longer (260 vs 215 min; p = 0.000), but length of stay was
      shorter (6 vs 8 days; p = 0.014), and thirty-day readmission rate was lower (6.3%
      vs 19.7%; p = 0.033). CONCLUSIONS: In this study population, robotic rectal
      surgery in obese patients resulted in a shorter length of stay and lower 30-day
      readmission rate but longer operative time when compared to laparoscopic surgery.
      Robotic rectal surgery in the obese may be associated with a quicker post
      operative recovery and reduced morbidity profile. Larger-scale multi-centre
      prospective observational studies are required to validate these results.

PMID- 29577171
TI  - Social inequalities in the association between temperature and mortality in a
      South European context.
AB  - OBJECTIVES: To analyse social inequalities in the association between ambient
      temperature and mortality by sex, age and educational level, in the city of
      Barcelona for the period 1992-2015. METHODS: Mortality data are represented by
      daily counts for natural mortality. As a measure of socioeconomic position, we
      used the educational level of the deceased. We also considered age group and sex.
      We considered, as a measure of exposure, the daily maximum temperatures. Time
      series Poisson regression with distributed lag non-linear models was fitted for
      modelling the relationship between temperature and mortality. RESULTS: Women had
      higher risk of mortality by hot temperatures than men. Temperature-mortality
      association (heat and cold) was evident for the elderly, except for heat-related
      mortality in women which was present in all age groups. Men with primary
      education or more were more vulnerable to moderate or extreme temperatures than
      those without studies. Finally, women were vulnerable to heat-related mortality
      in all educational levels while women without studies were more vulnerable to
      cold temperatures. CONCLUSIONS: Social and economic individual characteristics
      play an important role in vulnerability to high and low temperatures. It is
      important that decision-making groups consider identified vulnerable subgroups
      when redacting and implementing climate change resilience and adaptation plans.

PMID- 29577172
TI  - Parafoveal and optic disc vessel density in patients with obstructive sleep apnea
      syndrome: an optical coherence tomography angiography study.
AB  - AIMS: To compare optic disc perfusion, radial peripapillary capillaries (RPC) and
      macular vascular density, between normal subjects and subjects with obstructive
      sleep apnea syndrome (OSAS) using spectral-domain OCT angiography (OCTA).
      METHODS: Sixteen eyes of patients with mild OSAS, 17 eyes with moderate OSAS, 20
      eyes with severe OSAS on polygraphy and 28 controls were evaluated with OCTA RT
      XR Avanti (AngioVue software, Optovue Inc., Fremont, CA). Optic nerve head (ONH),
      RPC and macular vessel density were measured. Clinical data, visual field
      parameters, and Spectral Domain OCT evaluation (retinal nerve fiber layer (RNFL)
      thickness and ganglion cell complex (GCC) thickness) were recorded for all
      patients. RESULTS: ONH vascular flow (p = 0,396), RPC vascular density
      (automatized data "whole" p = 0,913, "peripapillary" p = 0,539, and segmented
      analysis with a topographic grid) and macular vascular density (foveal p = 0,484,
      parafoveal p = 0,491) were not significantly different between the four groups.
      FDT-MatrixTM and Humphrey 24/2 mean deviation were significantly lower in eyes
      with severe OSAS and were correlated to the apnea-hypopnea index. Retinal nerve
      fiber layer (RNFL) thickness, Cup/Disc ratio, rim area, and ganglion cell complex
      (GCC) were not significantly modified. CONCLUSIONS: OCTA did not detect reduced
      ONH, RPC, neither macular blood vessel density in eyes with OSAS. The precise
      mechanisms that link OSAS with optic nerve pathologies remain unclear: our study
      was not able to demonstrate a vascular impact by OCTA examination.

PMID- 29577173
TI  - Effect of replacing concentrate feed with leaves of Oldman saltbush (Atriplex
      nummularia) on feed intake, weight gain, and carcass parameters of highland sheep
      fed on wheat straw in northern Ethiopia.
AB  - Atriplex nummularia (oldman saltbush) is widely planted on salt-affected land to
      provide a vegetative cover, which can be used as an alternative feed resource.
      The study was conducted to evaluate the replacement of commercial concentrate
      with oldman saltbush (SB) leaf on the feed intake, live weight gain, and carcass
      parameters of local sheep. Twenty-five sheep with an age of 6 months and
      weighting 14.60 +/- 2.47 kg were used in randomized complete block design and
      distributed into five equal groups, with five animals each. The selected sheep
      were fed with the dietary treatments for 2 weeks for adaptation and continued
      until the end of the study, which lasted for 90 days. In the control treatment
      (SB-0), sheep were fed 100% concentrate mix, while in SB-5, SB-10, SB-15, and SB
      20, 5, 10, 15, and 20% of the concentrate mix was replaced by SB, respectively.
      Wheat straw and water were given at ad libitum throughout the experiment period.
      Data on feed intake and live weight gain were recorded daily and weekly,
      respectively, for 90 days. Three animals from each treatment were slaughtered for
      carcass analysis. Atriplex nummularia leaf (Oldman saltbush) contained 92.02% dry
      matter (DM), 21.99% crude protein (CP), 24.77% ash, 58.27% neutral detergent
      fiber (NDF), and 26.56% acid detergent fiber (ADF). Dry matter intake, live
      weight gain, and carcass parameter were not statistically different among the
      treatments. Result indicated that concentrate feed can be replaced with Atriplex
      nummularia leaf up to 20% in sheep diet without negative effect on growth
      performance and carcass characteristics.

PMID- 29577175
TI  - Toward eradicating misconceptions on matching in etiological studies.

PMID- 29577174
TI  - Non-associative learning processes in vestibular nucleus.
AB  - Simple non-associative learning processes, habituation and sensitization, are
      known to be systemically involved in different neurotransmissions, and these
      processes in the vestibular nucleus (VN) often show opposite responding patterns
      to repeated stimuli. However, their roles and mechanisms of the reciprocal
      responses at the cellular level are still elusive. Here, we conducted an
      electrophysiological experiment to investigate the neuronal responses to repeated
      stimuli in the VN, characterizing the neuronal responding patterns of habituation
      and sensitization. Based on our results, we also suggested an alternative
      hypothesis that these non-associative neuronal responses generated biased neural
      information based on simple linear addition. Sixty-seven neuronal responses to
      repeated stimuli were recorded from 23 guinea pigs, and the habituated and the
      sensitized responses were 37 (range of slopes - 3.66~- 0.02 spks/s/trial) and 30
      (0.01~1.51 spks/s/trial), respectively. Unlike previous study, the general
      neuronal responding shapes were not exponential, but most (94%, 63/67) responding
      profiles were linear. Although no strong relation between the irregular and the
      high sensitivity in our population, the neuronal irregularity and sensitivity
      could be the core factors to cause the biased results to more habituated side. In
      conclusion, we found that a biased neural response (mean +/- STD - 0.22 +/- 0.89
      spks/s/trial) was constructed by two non-associative neuronal responses based on
      a linear addition of the slopes. Graphical abstract Hypothesized and calculated
      neural mediation by non-associative learning processes.

PMID- 29577176
TI  - Glutamate receptors of the A5 region modulate cardiovascular responses evoked
      from the dorsomedial hypothalamic nucleus and perifornical area.
AB  - To assess the possible function of glutamate in the interaction between the
      dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine
      region (A5), cardiovascular and respiratory changes were studied in response to
      electrical stimulation of the DMH-PeF (1 ms pulses, 30-50 MUA given at 100 Hz for
      5 s) before and after the microinjection of kynurenic acid (non-specific
      glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist;
      50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG
      (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region.
      DMH-PeF electrical stimulation elicited a pressor (p < 0.001) and tachycardic
      response (p < 0.001) which was accompanied by an inspiratory facilitation
      characterised by an increase in respiratory rate (p < 0.001) due to a decrease in
      expiratory time (p < 0.01). Kynurenic acid within the A5 region decreased the
      tachycardia (p < 0.001) and the intensity of the blood pressure response (p <
      0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into
      the A5 region, the magnitude of the tachycardia and the pressor response were
      decreased (p < 0.05 and p < 0.01; p < 0.001 and p < 0.05, respectively). After
      MCPG microinjection into the A5 region, a decrease in the tachycardia (p < 0.001)
      with no changes in the pressor response was observed during DMH-PeF stimulation.
      The respiratory response elicited by DMH-PeF stimulation was not changed after
      the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region.
      These results suggest that A5 region glutamate receptors play a role in the
      cardiovascular response elicited from the DMH-PeF. The possible mechanisms
      involved in these interactions are discussed.

PMID- 29577178
TI  - Recurrent Adult Intraabdominal Undifferentiated High-Grade Pleomorphic Sarcoma
      Infiltrated the Descending Colon: a Case Report and Review of the Literature.

PMID- 29577177
TI  - Ocular Pharmacokinetics of 25-Hydroxyvitamin D3 After Weekly Supplementation in
      Rabbits Using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometer.
AB  - BACKGROUND AND OBJECTIVES: The protective role of vitamin D supplementation has
      recently been shown to be present in various ocular inflammatory diseases. The
      oral supplementation of vitamin D may take time to achieve adequate levels in
      intraocular fluids. Therefore, the present study was performed to understand the
      ocular pharmacokinetics of 25-hydroxyvitamin D3 (25D3) in aqueous humor after
      weekly supplementation of 25D3 in rabbits. METHODS: A total of 21 rabbits were
      fed orally with 25D3 (7.22 ug/kg/week) for 8 weeks and 9th dose was given at the
      end of 8 weeks. The blood and aqueous humor samples were collected from ear vein
      and though anterior chamber paracentesis, respectively. The serum and aqueous
      humor samples were spiked with deuterium labeled internal standard and were
      extracted using liquid extraction method. Furthermore, the samples were
      derivatized and 25D3 estimation was performed using ultra performance liquid
      chromatography-tandem mass spectrometer (UHPLC-MS/MS). RESULTS: The 25D3
      supplementation significantly increased the 25D3 levels in serum (78.5 +/- 21.6
      ng/ml) (mean +/- SD) (p < 0.0001) and in aqueous humor (991.3 +/- 180.6 pg/ml)
      (mean +/- SD) (p < 0.0001) compared to baseline levels. The maximum concentration
      was achieved in serum after the 10th hour of supplementation of 1st and 9th dose,
      while the same was observed at the 24th hour in aqueous humor. CONCLUSION: The
      oral supplementation of 25D3 was found to significantly increase 25D3 levels in
      aqueous humor; however, the time required to achieve 25D3 concentration in
      aqueous humor was higher as compared to that in serum. Therefore, weekly oral
      supplementation of 25D3 may have a beneficial role in ocular diseases.

PMID- 29577179
TI  - Novel Variants and Copy Number Variation in CDH1 Gene in Iranian Patients with
      Sporadic Diffuse Gastric Cancer.
AB  - INTRODUCTION: The aim of this study was to survey the nucleotide changes and copy
      number variations (CNV) in the CDH1 gene in Iranian patients with sporadic
      diffuse gastric cancer (SDGC). MATERIALS AND METHODS: In this study, 28 patients
      were examined who upon gastrectomy had been diagnosed with SDGC according to the
      familial history and histopathological criteria which was confirmed by the
      pathologist. DNA extraction was performed from formalin-fixed paraffin-embedded
      tissues using a phenol-chloroform method following xylene deparaffinization.
      Determination of DNA sequence by Sanger was performed using PCR amplification of
      16 exons and boundaries of intron/exon of CDH1 gene. Multiplex ligation-dependent
      probe amplification (MLPA) was performed on patients with pathogenic disorders in
      the sequence. RESULTS: In total, patients included 20 males and 8 females. Of all
      patients, 12 patients were under 45 years old (early onset gastric cancer, EODC)
      and 16 patients were older. The tumor was diagnosed in the early TNM stage (I,
      II) in six patients and in late stages (III, IV) in 19 cases. Altogether, 16
      variants (three exonic with one new variant and 13 intronic with nine new
      variants) were found in DNA sequencing of the CDH1 gene in five samples. Also,
      using MLPA, a new duplication in exon 9 and one deletion in exon 2 were detected
      in two other patients. Altogether, CDH1 variants were identified in seven out of
      28 patients (25%). CONCLUSION: Our study revealed several novel somatic variants
      in the CDH1 gene in Iranian patients with sporadic diffuse GC. Our data supports
      the hypothesis that mutations in CDH1 gene, and particularly the mutations we
      describe, should be considered, even in sporadic cases of gastric cancer. The
      presence of these mutations in patients raises important issues regarding genetic
      counseling and diagnostic test in DGC patients.

PMID- 29577180
TI  - Gastroesophageal Cancer During Pregnancy: a Case Report and Review of the
      Literature.

PMID- 29577181
TI  - A Comparative Evaluation of Presepsin with Procalcitonin and CRP in Diagnosing
      Neonatal Sepsis.
AB  - The objectives of this study were to study the clinical and biochemical profile
      of neonates with sepsis and to evaluate the diagnostic role of presepsin and its
      comparison with C-reactive protein (CRP) and Procalcitonin (PCT). This study was
      conducted from March 2015 through October 2016 in Neonatal intensive care unit
      (NICU) at S N Medical College, Agra. Neonates with >=1 clinical features of
      sepsis and/or two risk factors were included. A total of 41 cases and 41 controls
      were taken. Blood sample was taken for all investigations. ROC curve analysis was
      performed. Out of 41 cases, 19 were blood culture positive, majority were males
      (68.3%), low birth weight (LBW: 70.7%) and preterms (53.6%). At chosen cut-off
      values, sensitivity of CRP, PCT and presepsin was 80.5%, 80.5%, 97.6% and
      specificity was 97.5%, 80.5%, 95.1% respectively. PCT and CRP were comparable as
      diagnostic markers of neonatal sepsis. Presepsin, in comparison with CRP and PCT
      has better sensitivity and negative predictive value (NPV).

PMID- 29577182
TI  - Mercury Bioaccumulation in Tropical Mangrove Wetland Fishes: Evaluating Potential
      Risk to Coastal Wildlife.
AB  - The present study, aimed at observing the total concentration of mercury (Hg) in
      edible finfish species with an implication to human health risk, was carried out
      from the Setiu mangrove wetlands on the east coast of Peninsular Malaysia. Out of
      20 species observed, the highest Hg concentrations were found among carnivores
      fish/invertebrate-feeders, followed by omnivores and carnivores-invertebrate
      feeders, while the lowest concentrations in herbivores. The Hg concentrations
      varied widely with fish species and body size, from 0.12 to 2.10 mg/kg dry
      weight. A positive relationship between body weight and Hg concentration was
      observed in particular for Toxotes jaculatrix and Tetraodon nigroviridis. Besides
      the permissible range of Hg concentration up to 0.3 mg/kg (cf. United States
      Environmental Protection Agency (USEPA)) in majority of species, the carnivore
      feeders such as Acanthopagrus pacificus, Gerres filamentosus, and Caranx
      ignobilis have shown excess amounts (> 0.40 mg/kg flesh weight) that raising
      concerns over the consumption by local people. However, the weekly intake of
      mercury-estimated through the fish consumption in all three trophic levels
      suggests that the present Hg concentrations are still within the range of
      Provisional Tolerable Weekly Intake (PTWI) reported by the Joint FAO/WHO Expert
      Committee on Food Additives (JECFA). Perhaps, a multi-species design for Hg
      monitoring at Setiu wetlands would be able to provide further insights into the
      level of toxicity transfer among other aquatic organisms and thereby a strong
      health risk assessment for the local communities.

PMID- 29577184
TI  - Endogenous Regulators of the Immune System (sCD100, Malonic Dialdehyde, and
      Arginase).
AB  - Tissue damage in various diseases, hypoxic conditions, and some pathologies are
      associated with production of endogenous factors such as the soluble form of the
      surface receptor CD100, malonic dialdehyde, and arginase and their release into
      circulation. These factors modulate functional state of lymphocytes in the immune
      system: potentiate activation of B lymphocytes, activate synthesis and secretion
      of IL-25 and IL-17 cytokines, and suppress proliferative activity of T
      lymphocytes, thus modulating immunological reactivity of the organism. Reactions
      of innate and adaptive immunity develop against the background of changed
      immunological reactivity, which should be taken into account in the development
      of pathogenetically substantiated therapy.

PMID- 29577183
TI  - Developing novel methods to image and visualize 3D genomes.
AB  - To investigate three-dimensional (3D) genome organization in prokaryotic and
      eukaryotic cells, three main strategies are employed, namely nuclear proximity
      ligation-based methods, imaging tools (such as fluorescence in situ hybridization
      (FISH) and its derivatives), and computational/visualization methods. Proximity
      ligation-based methods are based on digestion and re-ligation of physically
      proximal cross-linked chromatin fragments accompanied by massively parallel DNA
      sequencing to measure the relative spatial proximity between genomic loci.
      Imaging tools enable direct visualization and quantification of spatial distances
      between genomic loci, and advanced implementation of (super-resolution)
      microscopy helps to significantly improve the resolution of images. Computational
      methods are used to map global 3D genome structures at various scales driven by
      experimental data, and visualization methods are used to visualize genome 3D
      structures in virtual 3D space-based on algorithms. In this review, we focus on
      the introduction of novel imaging and visualization methods to study 3D genomes.
      First, we introduce the progress made recently in 3D genome imaging in both fixed
      cell and live cells based on long-probe labeling, short-probe labeling, RNA FISH,
      and the CRISPR system. As the fluorescence-capturing capability of a particular
      microscope is very important for the sensitivity of bioimaging experiments, we
      also introduce two novel super-resolution microscopy methods, SDOM and low-power
      super-resolution STED, which have potential for time-lapse super-resolution live
      cell imaging of chromatin. Finally, we review some software tools developed
      recently to visualize proximity ligation-based data. The imaging and
      visualization methods are complementary to each other, and all three strategies
      are not mutually exclusive. These methods provide powerful tools to explore the
      mechanisms of gene regulation and transcription in cell nuclei.

PMID- 29577185
TI  - Variability of the Expression of Reference Genes in Samples of Human Olfactory
      Epithelium.
AB  - We analyzed variability of the expression of three reference genes in biopsy
      samples of the olfactory epithelium obtained from healthy volunteers. The
      expression of B2M, HPRT1, and CASC3 genes was analyzed by real-time PCR. The
      pairs of genes B2M-HPRT1 and B2M-CASC3 were found to possess minimum individual
      variability of expression and can be reliable candidates for the reference genes
      in analysis of gene expression in neural cells.

PMID- 29577186
TI  - Antitumor Activity of Fascaplysin Derivatives on Glioblastoma Model In Vitro.
AB  - Antitumor efficiency of fascaplysin synthetic derivatives (7-phenylfascaplysin, 3
      chlorofascaplysin, 3-bromofascaplysin, and 10-bromofascaplysin) was compared out
      in vitro on C6 glioma cells. The cytotoxic efficiency of all tested compounds was
      higher than that of unsubstituted fascaplysin; 3-bromofascaplysin and 7
      phenylfascaplysin exhibited the best capacity to kill glioma C6 cells. Apoptosis
      was the main mechanism of glioma cell death. The cytotoxic activity of these
      compounds increased with prolongation of exposure to the substance and increase
      of its concentration. Fascaplysin derivatives modified all phases of glioma cell
      vital cycle. The count of viable tumor cell in G0 phase remained minimum by the
      end of experiment under the effects of 3-bromofascaplysin and 7
      phenylfascaplysin.

PMID- 29577187
TI  - Combined Action of PGRPs-Hsp70 Cytotoxic Complex with Paclitaxel Improves
      Outcomes of Melanoma Treatment in Mice.
AB  - We studied the effect of PGRPs-Hsp70 cytotoxic complex that is analogous to
      natural complex secreted by cytotoxic lymphocytes and the antitumor drug
      paclitaxel on the development of M3 melanoma in DBA mice. Significant inhibition
      of tumor growth was observed in all experimental groups by days 20 and 35 of
      observation; paclitaxel monotherapy was less effective than administration of
      PGRPs-Hsp70 cytotoxic complex and its combination with paclitaxel. Pairwise
      comparison of Kaplan-Meier curves showed that survival was maximum in the group
      receiving combined therapy with PGRPs-Hsp70 cytotoxic complex and paclitaxel in
      comparison with groups receiving monotherapy.

PMID- 29577188
TI  - Decrease in Bcl-2 Protein Level during the Development of Lewis Carcinosarcome.
AB  - We studied the development of Lewis carcinoma and possible antitumor effect of
      preliminary administered antioxidant anphen. The tumor was intramuscularly
      transplanted to C57Bl*DBA mice (7*106 cells per mouse). According to
      immunoblotting results, the content of anti-apoptotic Bcl-2 protein steadily
      decreased starting from post-transplantation day 11. In few days, its content
      decreased by 15-20% and soon the animals died. After administration of anphen,
      the content of Bcl-2 decreased more rapidly than in the control. Atomic force
      microscopy revealed a decrease in the mean volume of erythrocytes and then
      increase in this parameter at the terminal stage of tumor growth. These findings
      suggest that anphen does not affect the tumor growth rate and mouse lifespan, but
      enhances apoptosis of blood cells of animals with Lewis carcinoma at the terminal
      stages of tumor growth.

PMID- 29577189
TI  - Effect of Various Treatment Modes of Experimental Mammary Gland Tumor on
      Structure of Anterior Mediastinal Lymph Nodes.
AB  - The effects of various treatment modes on the morphology of anterior mediastinal
      lymph nodes were examined in female Wistar rats with chemically provoked breast
      cancer. Adjuvant chemotherapy impaired filtration barrier potential of the
      anterior mediastinal lymph nodes, which manifested in increased volume of
      sinuses, reduced volumes of lymphoid nodules with germinal centers and thymus
      dependent regions, down-regulated proliferative activity of lymphoid cells in B
      cell zone and paracortex, and diminished macrophage score in all zones.
      Intraperitoneal injection of double-stranded DNA preparation (5 mg/kg) activated
      the humoral and cellular immune responses manifested by morphological alterations
      in anterior mediastinal lymph nodes observed in parallel with a decrease of
      medullary sinuses volume: enhancement of lymphocyte volume and lymphocyte score
      in paracortex, mantle zone expansion, and an increase of volume of the light
      centers in lymphoid nodules paralleled with diminished proliferative activity in
      them.

PMID- 29577190
TI  - Re-Examination of the Esophageal Squamous Cell Carcinoma Model in Rats Induced by
      N-Nitrososarcosine Ethyl Ester Precursors.
AB  - Studies of the molecular mechanisms of esophageal cancer development have to be
      carried out on sufficient amount of tumor material, obtained under conditions of
      controlled exposure to carcinogenic factors. Esophageal cancer models on
      laboratory animals serve an indispensable source of this material. One of these
      models is esophageal cancer induction in rats by N-nitroso compound precursors.
      Despite adequate reproduction of human esophageal cancer, this model in fact has
      not been used since the 1990ies. Re-examination of esophageal cancer model,
      induced by N-nitrososarcosine ethyl ester precursors, is carried out and its
      efficiency in induction of squamous cell carcinoma is confirmed.

PMID- 29577191
TI  - Effects of Electromagnetic Fields Modulated by Infralow Frequencies on the
      Production of Stem Cells.
AB  - Experimental validation of the method for regulation of stem cell proliferation
      and differentiation is carried out. The method consists in exposure to ultrahigh
      frequency electromagnetic radiation, modulated by infralow frequencies with
      variable parameters. A specially designed programmer, setting up the parameters
      of exposure, is connected to the source of radiation. The zones of anatomical
      location of the red bone marrow of rats were exposed for 15 min to the amplitude
      modulated electromagnetic radiation of ultrahigh frequency range. The parameters
      of exposure were determined in previous studies. The red bone marrow was
      collected from the sternum and head of the femur. The cellular composition of the
      red bone marrow was evaluated 1, 2, 3, and 6 days after the exposure. The optimal
      therapeutic mode of irradiation was then chosen, leading to stem cell activation
      with subsequent proliferation and differentiation into mature red bone marrow
      cells.

PMID- 29577192
TI  - Microscopic Study of Nervous System Plasticity: Interactions of Sympathetic
      Nerves with Neurons of Intraocular Hippocampal Transplants.
AB  - Functional interactions of sympathetic fibers innervating the iris with the
      neurons of central origin in intraocular transplants of the rat hippocampus were
      studied by optic, confocal, and electron microscopy. After formaldehyde fixation,
      fluorescent dye Dil was applied to the upper cervical ganglion; the dye migrated
      to the transplant by lateral diffusion via axons. Sympathetic nerves labeled with
      fluorescent dye grew into the neurotransplants along perivascular membranes of
      blood vessels. In addition, some fluorescent axons were identified in the
      transplant parenchyma. Electron microscopy showed large bundles of the peripheral
      type axons in the vascular adventitia and Schwann-axonal complexes in the
      transplant neuropil. Autonomic axons formed synaptic contacts with transplanted
      neurons.

PMID- 29577193
TI  - Changes in the Expression of Immune Proteasomes in the Liver after the Induction
      of Portal Tolerance Depending on Donor-Recipient Differences in Rats.
AB  - Induction of donor-specific tolerance in outbred Wistar rats (RT1u) and inbred
      August rats (RT1c) increased the expression of immune proteasome subunits in
      liver with a peak on day 7 after beginning of the induction. The increase in the
      level of immune subunits LMP2 and LMP7 was more pronounced in the liver of August
      rats in comparison with Wistar rats (by 2 and 6 times, respectively), which was
      associated with higher concentrations of monoamines in the CNS of August rats.
      After induction of donor-specific tolerance in August and Wistar rats, the immune
      subunits were in cells of sinusoidal lining and in cells located in sinusoid
      lumens. It can be suggested that immune proteasomes in these cells producing
      antigenic peptides for presentation to immunocompetent participate in the
      suppression of their activity and form the molecular basis for the development of
      donor-specific tolerance at very early stages of this process.

PMID- 29577194
TI  - Cytokine Production by Splenic Cells in C57BL/6J Mice with Depression-Like
      Behavior Depends on the Duration of Social Stress.
AB  - We studied the influence of depression-like behavior developed in C57BL/6J mice
      under conditions of social stress of different duration on cytokine production by
      splenic cells. Imbalance of the pro- and anti-inflammatory cytokines was detected
      at the early stage of depression-like behavior (10-day experience of defeats):
      increased production of proinflammatory IL-2 and IL-6 cytokines along with a
      decrease in anti-inflammatory IL-10 level; the levels of IL-1beta, TNFalpha,
      IFNgamma, and IL-4 remained unaffected. At later terms (20 days of
      confrontations), we revealed more pronounced changes in spontaneous production of
      proinflammatory cytokines that were not detected after shorter social stress.
      These findings suggest that cytokine profile depends on duration of social
      stress. Possible mechanisms of cytokine production during formation of depression
      like state are discussed.

PMID- 29577195
TI  - Role of IGFBP6 Protein in the Regulation of Epithelial-Mesenchymal Transition
      Genes.
AB  - Protein IGFBP6 plays an important role in the pathogenesis of many malignant
      tumors, including breast cancer. The relationship between IGFBP6 protein and the
      expression of genes associated with the epithelial-mesenchymal transition is
      studied. Gene IGFBP6 knockdown does not trigger the epithelial-mesenchymal
      transition in MDA-MB-231 cells, but modifies significantly the expression of many
      genes involved in this process. A decrease of IGFBP6 expression can involve a
      decrease in the expression of N-cadherin and transcription factor Slug.

PMID- 29577196
TI  - Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated
      Cerebral Neurons.
AB  - The concentration-clamp experiments with neurons isolated from the rat brain
      showed that nootropic and neuroprotective drug Semax added to perfusion solution
      at concentration of 1 MUM augmented the amplitude of GABA-activated ionic
      currents in cerebellum Purkinje cells by 147+/-13%. In addition, Semax in
      perfusion solution (0.1 and 1 MUM) diminished the amplitude of glycine-activated
      chloride currents in hippocampal pyramidal neurons down to 68 and 43% control
      level, respectively. Both potentiating and inhibitory effects developed slowly,
      and they were poorly reversible, which indicated a probable implication of second
      messengers in the observed phenomena. Semax accelerated the falling edge of
      glycine-activated current both after a short-term co-application with agonist and
      after addition of this peptide into perfusion solution.

PMID- 29577197
TI  - Signal Immune Reactions of Macrophages Differentiated from THP-1 Monocytes to
      Infection with Pandemic H1N1PDM09 Virus and H5N2 and H9N2 Avian Influenza A
      Virus.
AB  - In culture of THP-1 cells differentiated into macrophages with PMA (THP-PMA
      macrophages) infected with influenza viruses of subtypes H1, H5 and H9, we
      measured the expression of TLR7 and RIG1 receptor genes, sensors of viral RNA and
      ribonucleoprotein, and the levels of production of inflammatory cytokines IL
      1beta, TNFalpha, IL-10, and IFNalpha. The sensitivity and inflammatory response
      of THP-PMA macrophages to pandemic influenza A virus H1N1pdm09 and avian
      influenza H5N2 and H9N2 viruses correlate with the intracellular level of their
      viral RNA and activation of the RIG1 gene. Abortive infection is accompanied by
      intensive macrophage secretion of TNFalpha, IL-1beta, and toxic factors inducing
      cell death. Activity of endosomal TLR7 receptor gene changed insignificantly in
      24 h after infection and significantly decreased in 48 and 72 h under the action
      of H5N2 and H9N2, which correlated with manifestation of the cytopathogenic
      effect of these viruses. H5N2 and H9N2 avian viruses in THP-PMA macrophages are
      strong activators of the expression of the gene of the cytoplasmic RIG1 receptor
      24 and 48 h after infection, and the pandemic virus H1N1pdm09 is a weak
      stimulator of RIG1 gene. Avian influenza H5N2 and H9N2 viruses are released by
      rapid induction of the inflammatory response in macrophages. At the late stages
      of infection, we observed a minor increase in IL-10 secretion in macrophages and,
      probably, the polarization of a part of the population in type M2. The studied
      influenza A viruses are weak inductors of IFN in THP-PMA macrophages. In the
      culture medium of THP-PMA macrophages infected with H9N2 and H5N2 viruses, MTT
      test revealed high levels of toxic factors causing the death of Caco-2 cells. In
      contrast to avian viruses, pandemic virus H1N1pdm09 did not induce production of
      toxic factors.

PMID- 29577198
TI  - Study of the Oxime-induced Reactivation of Acetyl- and Butyrylcholinesterase of
      Human with Inhibition of Organophosphorus Insecticide In Vitro.
AB  - The efficiency of different reactivators of cholinesterase (toxogonin,
      dipiroxime, pralidoxime, carboxim, HI-6, and methoxime) at inhibition of
      butyrylcholinesterase and human acetylcholinesterase by organophosphate
      insecticide malathion was evaluated in in vitro experiments. Most reactivators
      increased inhibition of butyrylcholinesterase in comparison with the control, but
      HI-6 in a concentration of 10-3 mol/liter partially (10%) restored activity of
      the enzyme. Oxime-induced reactivation of acetylcholinesterase was most
      pronounced in dipyroxime and toxogonin: parameters of the kinetics of reduction
      of the phosphorylated enzyme differed by more than 2 times from the values
      received with the use of other reactivators.

PMID- 29577199
TI  - Experimental Analysis of the Efficacy of Dihydroquercetin on the Model of Chronic
      Nonbacterial Inflammation of the Prostatic Gland.
AB  - We studied the efficiency of dihydroquercetin on the model of chronic
      nonbacterial inflammation of the prostatic gland in rats. It was found that
      administration of dihydroquercetin was followed by a significant decrease in the
      area of the connective tissue in the prostatic gland to initial levels, which
      attested to antifibrotic properties of this oxidant. Additionally, the substance
      prevented the development of atrophy of acinus epithelium. After administration
      of reference drug Prostamol Uno, only moderate antifibrotic effects were
      observed.

PMID- 29577200
TI  - Role of Copper Dyshomeostasis in the Pathogenesis of Parkinson's Disease.
AB  - Serum concentration of copper, immunoreactive polypeptides of ceruloplasmin and
      its oxidase activity, and the number of copper atoms per ceruloplasmin molecule
      were decreased in patients with Parkinson's disease in comparison with the
      corresponding parameters in age-matched healthy individuals, but the ratio of
      apoceruloplasmin to holoceruloplasmin in patients with Parkinson's disease was
      similar in both groups. Treatment of blood serum with Helex 100, a high-affinity
      copper chelator, revealed reduced content of labile copper atoms per
      ceruloplasmin molecule in patients with Parkinson's disease in comparison with
      that in healthy controls. The mechanism underlying impaired metabolic
      incorporation of labile copper atoms into CP molecule is discussed as a possible
      cause of copper dyshomeostasis associated with Parkinson's disease.

PMID- 29577201
TI  - Effects of Fluoxetine and Potential Antidepressant 8-Trifluoromethyl 1,2,3,4,5
      Benzopentathiepin-6-Amine Hydrochloride (TC-2153) on Behavior of Danio rerio Fish
      in the Novel Tank Test and Brain Content of Biogenic Amines and Their
      Metabolites.
AB  - We compared the effect of a new potential antidepressant 8-trifluoromethyl
      1,2,3,4,5-benzopentathiepine-6-amine hydrochloride (TC-2153) and classical
      antidepressant fluoxetine in a dose of 0.25 mg/liter on the behavior of Danio
      rerio in the "novel tank" test and content of biogenic amines and their
      metabolites in the brain. Fluoxetine alone and TC-2153 alone significantly
      increased the time spent in the upper part of the tank and insignificantly
      reduced motor activity. Combined exposure of fishes in the solution containing
      potential and classical antidepressants potentiated their effects on both
      parameters. The compounds did not affect brain contents of serotonin, dopamine,
      and norepinephrine. At the same time, fluoxetine, but not TC-2153, reduced brain
      content of the main serotonin metabolite 5-hydroxyindole acetic acid.

PMID- 29577202
TI  - Compounds of IL-6 Receptor Complex during Acute Lung Injury.
AB  - Soluble receptor of IL-6 (sIL-6R) and antagonist of the receptor complex, soluble
      glycoprotein 130 (sgp130) mediate opposite effects during inflammation. We
      measured the levels of these cytokines and their ratio in rat blood on the model
      of acute lung injury. The injury was modeled by the intratracheal administration
      of LPS. The levels of sgp130 and sIL-6R increased during the inflammatory process
      in the injured lungs. The sgp130/sIL-6R ratio increased or decreased depending on
      the intensity of the inflammatory process. sgp130/sIL-6R ratio might reflect the
      intensity of inflammation during lung injury.

PMID- 29577203
TI  - Evaluation of DNA Damage in Experimental Preeclampsia by Comet Assay.
AB  - Experimental preeclampsia induced by substitution of drinking water with 1.8%
      NaCl during pregnancy was associated with an increase in the level of DNA damage
      in fetal brain and placenta measured by DNA comet assay by 35.7 and 27.8 times,
      respectively, in comparison with physiological pregnancy.

PMID- 29577204
TI  - fMRI Responses in Healthy Individuals and in Patients with Mild Depression to
      Presentation of Pleasant and Unpleasant Images.
AB  - Patients with mild depression and apparently healthy individuals were presented
      images and asked to sort them into "pleasant" and "unpleasant" subsets. In both
      groups, the main differences between brain activation patterns during
      presentation of pleasant and unpleasant images were localized in the motor
      regions (precentral and postcentral gyrus) and in the cerebellum (p<0.05 with FWE
      correction). Most likely, these clusters are associated with motion (pressing a
      button in accordance with the instruction). According to the data of intergroup
      contrasts, patients with depression had less pronounced activation of frontal
      structures (middle frontal gyrus and other areas, including the white matter) in
      response to both positive and negative images (p<0.001). In healthy subjects, the
      response of the temporo-occipital areas (lingual and fusiform gyrus) to
      unpleasant stimuli was more intensive than in patients (p<0.001). This can be due
      to differences in the semantic image processing. Thus, in case of mild
      depression, the response of the amygdaloid complex, the key structure in the
      development in affective disorder, was not always observed. At the same time, the
      response of frontal and temporo-occipital regions has a certain potential as a
      biomarker of mild depression, although the reliability of the obtained data
      requires additional confirmation.

PMID- 29577205
TI  - Influence of "Enriched Environment" on Behavior and Neurogenesis in Mice Selected
      by Cognitive Trait.
AB  - Mice selected for high score in the extrapolation test (EX line) and kept under
      conditions of "enriched environment" for 3 months demonstrated changes in
      locomotor and exploratory activity and enhanced reaction to novelty. The relative
      brain weight was higher and neurogenesis in the hippocampal fascia dentate was
      more intensive in this group. In non-selected mice, the changes were similar, but
      insignificant in many cases.

PMID- 29577206
TI  - Stress Response to Physical Exercise in Rats with Alimentary Obesity.
AB  - Stress response to physical exercise was studied in rats with alimentary obesity
      with and without caloric diet restriction. Daily excretion of corticosterone,
      progesterone, and testosterone, weights of internal organs, and serum levels of
      glucose, free fatty acids, triglycerides, corticosterone, and testosterone were
      estimated. Stress response to moderate exercise in rats with alimentary obesity
      was associated with predominance of anabolic influence of testosterone over the
      catabolic effects of corticosterone, which promoted the increase in the weight of
      reproductive organs. Exposure to physical loads against the background of
      restricted ration potentiated the response of the adrenocortical system and
      reduced the concentration and anabolic effects of testosterone.

PMID- 29577207
TI  - Assessment of Cardiac Vegetative Control during Acute Graduated Exogenous
      Normobaric Hypoxia in Rats.
AB  - The effects of exogenous normobaric hypoxic hypoxia on vegetative control of the
      heart and BP were examined in Wistar rats. The reference ranges of variation
      pulsometry parameters were determined in rats with normoxemia for 3 physiological
      variants of autonomic homeostasis: eutony, sympathicotony, and vagotony. Most
      rats (80%) demonstrated autonomic eutony. The study showed that saturation of
      arterial blood with oxygen is the most adequate assessment of severity of acute
      exogenous normobaric hypoxic hypoxia progressing within a closed hypoxic chamber,
      which standardizes this method and minimizes inaccuracies resulting from
      individual sensitivity to hypoxic stress. The changes in functional activity of
      systems that control the heart rhythm closely correlated with the drop in
      arterial blood oxygenation. While a small arterial hypoxemia activated the
      ergotropic elements of autonomic nervous system central subdivision accompanied
      by elevation of systolic BP, the moderate hypoxemia augmented the cholinergic
      influences and moderated the adrenergic ones under maintaining mobilization of
      the central autonomic nervous system-control loop and normotension. Severe
      hypoxemia was manifested by augmented influences from autonomic nervous system
      central subdivisions on the heart rate, disadaptation of the control systems, and
      systolic-diastolic arterial hypotension.

PMID- 29577208
TI  - Hematopoietic Stem Cell Transplantation for Adult Philadelphia-Negative Acute
      Lymphoblastic Leukemia in the First Complete Remission in the Era of Minimal
      Residual Disease.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the potential role of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia
      negative (Ph-) adult acute lymphoblastic leukemia (ALL) in first complete
      remission (CR1) in the era of minimal residual disease (MRD). RECENT FINDINGS:
      Allo-HSCT continues to have a role in the therapy of a selected group of high
      risk adult patients with ALL in CR1. Although the clinical significance of MRD
      has been studied less extensively in adults with ALL than in children, recent
      studies support its role as the strongest prognostic factor that can identify
      patients that are unlikely to be cured by standard chemotherapy and benefit from
      undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been
      found to correlate directly with the risk of relapse. Currently, the clinical
      challenge consists on applying MRD and molecular failure to integrate novel
      agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft
      versus leukemia (GVL) effect after transplant.

PMID- 29577209
TI  - [The necessary perseverance of surgery for the treatment of locally advanced
      colorectal cancer].
AB  - Colorectal cancer, a malignant tumor arising from the colon or rectum, is a
      common cancer in China, with most patients diagnosed at the advanced stage or
      locally advanced stage. Large tumor size results in the invasion of adjacent
      organs and the multiple organ involvement, which poses certain challenges for
      clinical treatment. When facing advanced stage colorectal cancer, some surgeons
      do not consider surgery, a reasonable option. However, in fact, multi
      disciplinary treatment can achieve relatively good treatment outcomes in patients
      with advanced stage or locally advanced stage colorectal cancer. Therefore,
      reasonable surgery should not be hastily abandoned. For patients with large
      tumors without distant metastases but with multiple organ involvement, directly
      surgical resection is difficult, therefore, preoperative adjuvant therapy can be
      considered. The basic principle of surgical treatment is to accomplish maximum
      protection of organ functions and to perform reasonable regional lymph node
      dissection on the basis of achieving R0 resection. Common surgical procedures for
      locally advanced colorectal cancer are as follows: (1)Right-sided colon cancer
      with duodenal invasion: first, the colon must be freed from three directions,
      namely the right posterior surface of the colon, the left side of the tumor, and
      the upper side of the tumor inferior to the pylorus, so as to expose and assess
      the spatial relationship between the tumor and the duodenum; the actual tumor
      invasion depth in the duodenum may be shallow. (2) Splenic flexure colon cancer
      with invasion of the cauda pancreatis and hilum lienis: multivisceral resection
      must be performed without separating the attachment between the tumor and spleen.
      The tumor border can be found more easily through manipulations starting from the
      descending colon. (3) Giant sigmoid colorectal cancer with bladder invasion:
      invasion usually occurs at the bladder fundus. Therefore, during surgery, the
      attachment between the rectum and the bladder must not be separated first, but
      instead, an assessment must be made to determine if the bladder trigone is
      involved. (4) Rectal cancer with invasion of the sacrum: sacral invasion below S3
      can be resected. The proximal end of the rectum to the point where it joins the
      sacrum is freed, and the rectum is severed. A permanent colostomy is made at the
      proximal end, while a h-shaped incision is made in the sacrum. The sacrum is then
      resected along pre-determined resection lines. (5) Rectal cancer with invasion of
      the uterus, adnexa, vagina, or prostate and seminal vesicles: it is usually
      observed in low rectal cancer. For unilateral ovarian involvement, combined
      resection of the bilateral adnexa should be performed. For vaginal involvement,
      combined resection of the vagina should be performed. For prostatic involvement,
      partial resection of the prostate can be performed. In general, when facing
      relatively complicated advanced or locally advanced colorectal cancer, clinical
      surgeons must adopt a positive attitude and strive zealously against the odds.
      With the support of multi-disciplinary treatment, the option of surgery must not
      be hastily abandoned in order to increase the survival chances of patients.

PMID- 29577210
TI  - [Transanal conformal resection for super low rectal cancer].
AB  - Intersphincteric resection(ISR) is a valuable anus-preserving operation that
      avoids the need for permanent stoma in patients with super low rectal cancer.
      Recently, with the application and promotion of ISR, the rate of anus
      preservation has been greatly elevated, however, some patients following ISR had
      poor anal function. Based on the knowledge of anal canal anatomical features for
      better anal function, we propose conformal sphincter-preserving operation (CSPO)
      for super low rectal cancer, which is a new integrated anus-preservation
      procedure with total mesorectal excision (TME), coloanal anastomosis, pull
      through resection, anal canal dissection, local resection and natural orifice
      transluminal endoscopic surgery technology. CSPO includes pull through conformal
      resection (PTCR) and transanal conformal resection (TaCR). This article focuses
      on the problems about TaCR for very low rectal cancer and introduces TaCR
      combined with our practical experience. The indications for the TaCR operation
      should be according to the conventional laparoscopic surgery. In addition, the
      TaCR operation has its special indications: the tumor location is within 2 cm of
      the dental line; the tumor is well differentiation (moderately to well
      differentiation); the diameter of the tumor is not more than 3 cm or no more than
      the 1/3 circle of intestinal wall; and the depth of invasion is T1-T2. Patients
      with a clinical complete remission after neoadjuvant radiochemotherapy can
      receive TaCR. The laparoscopic five hole method is used to carry out the
      abdominal operation with TME technique. It is unnecessary to dissection
      intersphincter space. The incisional line is made according to the tumor location
      and shape to preserve the opposite normal rectal wall, internal sphincter and
      dentate line as more as possible via transanal resection. After closing the
      rectal stump by interrupted sutures, a circular stapler or hand suture is use to
      perform the anastomosis as far from the dentate line as possible. Protective loop
      ileostomy is performed. Postoperative complications, including anastomotic
      leakage, abdominal infection, and anastomotic bleeding, should be remembered. If
      there is any signs of these complications, intervention should be done as soon as
      possible.

PMID- 29577211
TI  - [Transanal total mesorectal excision for low rectal cancer: pros and cons].
AB  - Colorectal cancer is the 3rd most commonly diagnosed cancer, with rectal cancer
      specifically accounting for 1/3 of new cases. Despite advances in care, there is
      still a lack of standardization in diagnosis, staging, and treatment, with
      associated high rates of positive margins, recurrence, and mortality. The gold
      standard for curative resection remains a total mesorectal excision(TME), and the
      quality of the TME is one of the most important prognostic factors for local
      recurrence. The proper TME specimen with negative resection margins is inherently
      challenging due to patient and tumour-related factors. These difficulties have
      not been overcome with the laparoscopic approach. Transanal TME (taTME) is an
      innovative surgical technique developed to overcome the limitations in exposure
      and instrumentation in low pelvic surgery by approaching the rectum from below.
      Interest in taTME continues to grow worldwide, and structured training programs
      and case registries have been developed to aid safe implementation of this new
      technique in clinical practice. As the utilization of taTME and indications for
      the procedure continue to expand, structured programs to standardize teaching,
      training, and safe expansion will aid the safe spread of the taTME technique.
      With the growing popularity, a review of the pros and cons of the taTME is
      timely.

PMID- 29577212
TI  - [Associated vessel heteromorphosis in laparoscopic complete mesocolic excision
      and solutions to intraoperative hemorrhage].
AB  - Vessel identification and dissection are the key processes of laparoscopic
      complete mesocolic excision (CME). Vascular injury will lead to complications
      such as prolonged operative time, intraoperative hemorrhage and ischemia of
      anastomotic stoma. Superior mesenteric artery (SMA), superior mesenteric
      vein(SMV), gastrointestinal trunk, left colic artery(LCA), sigmoid artery and
      marginal vessels in the mesentery have been found with possibility of
      heteromorphosis, which requires better operative techniques. Surgeons should
      recognize those vessel heteromorphosis carefully during operations and adjust
      strategies to avoid intraoperative hemorrhage. Preoperative abdominal computed
      tomography angiography(CTA) with three-dimensional reconstruction can find vessel
      heteromorphosis within surgical area before operation. Adequate dissection of
      veins instead of violent separation will decrease intraoperative bleeding and be
      helpful for dealing with the potential hemorrhage. When intraoperative hemorrhage
      occurs, surgeons need to control the bleeding by simple compression or vascular
      clips depending on the different situations. When the bleeding can not be stopped
      by laparoscopic operation, surgeons should turn to open surgery without
      hesitation.

PMID- 29577213
TI  - [Key vessels assessment and operation highlights in laparoscopic extended right
      hemicolectomy].
AB  - Laparoscopic radical colectomies have been more widely used gradually, among
      which laparoscopic extended right hemicolectomy is considered as the most
      difficult procedure. The difficulty of extended right hemicolectomy lies in the
      need to dissect lymph nodes along the superior mesenteric vein (SMV) and
      disconnect numerous and possible aberrant vessels. To address this problem, we
      emphasize two points in key vessel assessment: getting familiar with the anatomy
      along the medial-to-lateral approach and having a good understanding about the
      preoperative imaging presentations. An accurately preoperative imaging assessment
      by abdominal enhanced CT can help the surgeon understand the relative position of
      the key vessels to be dealt with during operation and the situation of the
      possible aberrant vessels so as to guide the procedure more effectively and
      facilitate the prevention and management of the intraoperative complications.
      During operation, the operator should pay special attention to the management of
      the vessels in the ileocolic vessel region, Henle's trunk and middle colon
      vessels. The operation highlights of the key vessels are as follows: (1) The
      ileocolic vessels: identifying the Toldt's gap correctly and opening the vascular
      sheath of the SMV securely; making sure that the duodenum is well protected. (2)
      Henle's trunk: dissecting along the surface of the Henle's trunk; preserving the
      anterior superior pancreaticoduodenal vein (ASPDV) and main trunk of the Henle's
      trunk; disconnecting the roots of the right colic vein (RCV) and right
      gastroepiploic vein (RGEV), and then dissecting lymph nodes along the surface of
      the pancreas. (3) The middle colon vessels: identifying the root of the middle
      colon vessel along the lower edge of the pancreas; avoiding entering behind the
      pancreas; mobilizing the transverse mesocolon sufficiently along the surface of
      the pancreas. Finally, we discuss and analyze the disputes currently existing in
      laparoscopic extended right hemicolectomy, including dissection of No.6 lymph
      nodes, naking the SMA and dissecting lymph nodes around the roots of the branches
      of SMA. This article shares our experience about laparoscopic extended right
      hemicolectomy, hoping that it could help beginners master the technique more
      safely and skillfully.

PMID- 29577214
TI  - [Significance of the preservation of left colic artery in laparoscopic resection
      of rectal cancer].
AB  - Controversy remains on how to manage left colic artery (LCA) when it comes to
      laparoscopic proctectomy. With regard to the level of detachment, a high tie of
      inferior mesenteric artery (IMA) is meant as a ligation at the origin of aorta,
      while the low tie is the ligation of IMA below the initiation part of left colic
      artery which is left. Several key points of LCA preservation, including clinical
      value, oncologic safety and the difficulty of operation, have always been
      debated. Some scholars hold the point of view that the preservation of LCA will
      hamper the lymph nodes dissection around the inferior mesenteric artery,
      resulting in incorrect pathological staging and dismal outcome. Of note, low tie
      prolongs the duration of operation and increases the anastomotic tension.
      However, increasing research results have established its clinical values. The
      value for reducing the risk of anastomotic leakage and the effect on the lymph
      nodes dissection at the root of inferior mesenteric artery will be discussed
      based on previous studies and our clinical practice. We came up with a novel
      concept of "the lymph nodes in the triangular domain of inferior mesenteric
      artery which consists of abdominal aorta, inferior mesenteric vein(IMV)/LCA and
      IMA" instead of traditional No.235 lymph nodes. In our innovative approach of
      total mesorectal excision guided by vessel, a crack was made at the root of aorta
      and the dissection was performed along IMA, reaching the origin of LCA. The lymph
      nodes will be harvested as a whole. After achieving process standardization,
      vessel-oriented approach and left colic artery preservation makes this region
      susceptible to lymphadenectomy, protecting submesenteric plexus and guarantying
      the oncological safety without increasing operative difficulty.

PMID- 29577215
TI  - [Current status in surgical treatment of constipation].
AB  - Chronic constipation is a polysymptomatic heterogeneous disorder with the
      incidence rising in many countries, and becomes a common disease affecting the
      quality of life and financial burden. In China surgical guideline, the primary
      constipation is divided into 3 types: slow transit constipation, outlet
      obstructive constipation, mixed constipation. The Rome IIII( criteria is usually
      referred to diagnosis, considering with clinical features and patient complaints.
      Through detail interrogation, physical examination and various detections, the
      secondary causes should be excluded, and etiological treatment is worth to try.
      Surgery is generally recommended as the second-line therapy, and finally only few
      patients require operation. There are still several controversies over the choice
      of surgical procedures and the mode of anastomosis in patients with slow transit
      constipation. Common surgical procedures include total colectomy with ileorectal
      anastomosis (TAC-IRA), subtotal colectomy with ileosigmoid anastomosis,
      ileorectal anastomosis or cecal-rectal anastomosis. Now laparoscopic operations
      have been widely applied to these patients, and have achieved good efficacy, and
      the application of robots is also under exploration. With the outlet obstructive
      constipation complicated pathogeny, the mechanisms currently involved include
      paradoxical puborectalis contraction, increased perineal descent, rectal
      intussusception, rectocele and rectal prolapse. In recent years, aiming at the
      above mechanisms, variety of surgical methods has been explored, including
      bilateral partial resection of puborectalis (PDPR) for paradoxical puborectalis
      contraction, rectal mucosa longitudinal plication plus sclerosing agent
      injection, procedure for prolapse and hemorrhoids (PPH), rectal mucosal resection
      and muscle plication procedure (Delorme), stapled transanal rectal resection
      (STARR) and laparoscopic ventral mesh rectopexy (LVR) etc for rectal prolapse.
      However, there is still no long-term large sample study to prove the advantages
      and disadvantages of these operations, so operative procedure should be chosen
      according to the actual situation of the patient. With the integration of the
      pathogenesis and the diversification of the treatment methods, the constipation
      still needs the precise treatment combined with multidisciplinary support in the
      future.

PMID- 29577216
TI  - [Application of inner figure-of-eight suture to laparoscopic colorectal surgery].
AB  - Regardless of laparoscopic or open colorectal surgeries, intestinal anastomosis
      is usually an important operative procedure. Even if stapler is widely used in
      different intestinal surgery nowadays, hand sewn suture is an indispensable
      procedure in clinical practice, meanwhile after stapled anastomosis, additional
      hand sewn suture is usually performed to ensure the safety of anastomosis. The
      inner figure-of-eight suture is a single layer suture technique which has been
      widely used in skin, tendon, rectus and uterus for quick and secure
      approximation. We describe our innovative application of inner figure-of-eight
      suture technique for intestinal anastomosis and/or reinforcement after stapled
      anastomosis in laparoscopic colorectal surgery. Main steps of inner figure-of
      eight suture for intestinal anastomosis on posterior wall are as follows: (1) At
      4 mm from cut edge of bowel, needle enters vertically from one side and courses
      mucosa-serosa-opposite serosa-mucosa in parallel to the entry point. (2) The
      needle is brought back to first entry side of bowel at 45 degree to enter the
      mucosa 5 mm below the first entry point and out on opposite side mucosa
      horizontally. (3) Both lose ends of the suture are pulled to approximate bowel
      edges and knots are tied on mucosal surface, in which suture line presents figure
      of-eight on mucosal surface and two parallel suture lines are seen on serosal
      surface. When inner figure-of-eight suture is performed on anterior wall, the
      procedure is similar, but needle passes from serosa-mucosa-opposite mucosa-serosa
      and repeated to complete the inner figure-8 suture and knots are tied on serosa.
      The final look is two parallel sutures at 0.5 mm in between and the figure-of
      eight remains inside the lumen. We did not deliberately try to invert the bowel
      edges, and if anastomosis is not satisfactory at final examination, simple
      interrupted seromuscular suture can be carried out. From 2015 till now, we have
      successfully completed inner figure-of-eight sutures in 38 cases receiving
      intestinal anastomosis reinforcement procedure and in 24 cases receiving hand
      sewn anastomosis. Comparison study revealed inner figure-of-eight suture
      presented shorter anastomotic time and less medical cost without anastomotic
      leakage, stump leakage or bleeding. No anastomotic stenosis was found at
      enteroscopy examination during follow up. We think that inner figure-of-eight
      suture possesses safe and simple advantages and is a manual suture technique
      worthy of promotion.

PMID- 29577217
TI  - [Impact of previous abdominal surgery on the outcomes of laparoscopic resection
      for colorectal cancer].
AB  - OBJECTIVE: To investigate the effect of previous abdominal surgery(PAS) on
      laparoscopic resection of colorectal cancer. METHODS: The retrospective cohort
      study was adopted.Clinical data of consecutive colorectal cancer patients with
      PAS history (past history of at least one abdominal surgery, exclusion of
      previous inguinal hernia repair, simple laparoscopic approach, appendectomy of
      the right lower quadrant and endoscopic therapy) undergoing laparoscopic surgery
      at the Cancer Hospital of Chinese Academy of Medical Sciences between 2010 and
      2015 were collected, meanwhile other colorectal cancer patients without PAS
      history were selected according to 1 to 1 match in age, sex, body mass index,
      American Society of Anesthesiologists score, tumor location, type of surgery, and
      staging of tumor. A total of 464 pairs were successfully matched. Intraoperative
      and postoperative conditions, perioperative complications and prognosis were
      compared between the two groups. RESULTS: In PAS group, there were 341 males
      (73.5%) and 123 females (26.5%) with a median age of 62 (24-85) years; 317(68.3%)
      cases with only one previous abdominal surgery and 147(31.7%) with more than one;
      389(83.8%) cases with abdominal midline incisions, 37(8.0%) with transverse
      incisions, 34(7.3%) with right subcostal incision and 4(0.9%) with left subcostal
      incision; 146(31.5%) cases undergoing gynecologic surgery, 84(18.1%)
      cholecystectomy, 52(11.2%) gastroduodenal surgery, 89(19.2%) colorectal surgery,
      11(2.4%) small intestine surgery, 23(5.0%) hapatectomy, 16(3.4%) pancreatic
      surgery, 8(1.7%) urological surgery, 18(3.9%) retroperitoneal tumor resection and
      1(0.2%) other surgery. In no PAS group, there were 328 males (70.7%) and 136
      females (29.3%) with a median age of 62(24-86) years. No significant differences
      in baseline data were found between the two groups (all P>0.05). As compared to
      no PAS group, PAS group had longer mean operative time [(208.0+/-27.0) minutes
      vs. (179.0+/-15.3) minutes, t=4.695, P=0.003] and higher rate of conversion to
      laparotomy [18.1%(84/464) vs. 11.6%(54/464), chi2=7.217, P=0.003]. In the PAS
      group, conversion to laparotomy was more common due to adhesion reaction
      [8.8%(41/464) vs. 4.5%(21/464), chi2=4.886, P=0.007]. There were no significant
      differences between the two groups in intraoperative bleeding and transfusion,
      lymph node dissection, circumferential margin and surgical margin, time to the
      first diet and postoperative hospital stay(all P>0.05). No significant
      differences in intraoperative and postoperative morbidity of complication were
      found between PAS group and no PAS group [3.7%(17/464) vs. 2.8%(13/464), P=0.346;
      20.3%(94/464) vs. 18.5%(86/464), P=0.739]. Median follow-up of the whole patients
      was 32.0(0.5-79.0) months, and there was no significant difference between the
      two groups [PAS group 31.0(0.5-79.0) months vs. no PAS group 33.0(1.0-75.0)
      months, P=0.391]. In PAS and no PAS group, the 3-year disease-free survival rate
      was 68.1%(95%CI: 62.0%-74.2%) and 68.5%(95%CI: 63.0%-74.0%)(P=0.764), and 3-year
      overall survival rate was 78.5%(95%CI: 72.8%-81.4%) and 80.2%(95%CI:74.3%
      86.1%)(P=0.528) respectively, whose differences were not significant. CONCLUSION:
      Except higher risk of conversion to laparotomy due to adhesion reaction,
      laparoscopic resection of colorectal cancer is safe and feasible in patients with
      PAS, and the prognosis is not affected by PAS.

PMID- 29577218
TI  - [Application of Overlap method to digestive tract reconstruction of totally
      laparoscopic left colectomy].
AB  - OBJECTIVE: To investigate the application value of the Overlap method in
      digestive tract reconstruction of totally laparoscopic left colectomy(TLLC) and
      its potential advantage. METHODS: The retrospective cohort study was adopted.
      Clinicopathological data of 16 patients with left colon cancer who underwent TLLC
      and Overlap anastomosis between August 2016 and August 2017 at Tangdu Hospital
      were retrospectively collected as Overlap group. Twenty-one patients who
      underwent laparoscopic assisted left colectomy (LALC) between January 2015 and
      July 2016 at Tangdu Hospital were used as control (traditional group). The
      intraoperative and postoperative data were compared between the two groups.
      During digestive tract reconstruction in the Overlap group, the proximal colon
      and distal colon were lined up side by side; a side-to-side anastomosis was
      conducted on colic band with a 60 mm linear stapler; and the common entry hole
      was closed using running suture. While in traditional group, the bowel was pulled
      out of abdominal wall through the assisted incision; the sample was resected and
      a proximal and distal end-to-end anastomosis was performed. RESULTS: In Overlap
      group, 10 cases were male and 6 cases were female, with a mean age of (66.4+/
      4.8) years and a BMI of (23.6+/-2.3) kg/m2; the tumor located in distal
      transverse colon in 1 case, in splenic flexure in 2 cases, in descending colon in
      4 cases, in upper sigmoid colon in 9 cases. TLLC was successfully completed in
      all the cases without conversion to laparotomy. In traditional group, 12 cases
      were male and 9 cases were female, with mean age of (65.9+/-5.8) years and BMI of
      (22.7+/-2.8) kg/m2; the tumor located in the distal transverse colon in 1 case,
      in the splenic flexure in 3 cases, in the descending colon in 6 cases, in the
      upper sigmoid colon in 11 cases. No statistically significant differences in
      baseline data were found between the two groups (all P>0.05). Compared to the
      traditional group, the total operation time was shorter [(143.4+/-11.1) minutes
      vs. (166.4+/-16.5) minutes, t=4.792, P=0.000], the anastomosis time was prolonged
      [(44.3+/-3.3) minutes vs. (22.4+/-3.0) minutes, t=-20.948, P=0.000], the amount
      of bleeding was reduced [(46.6+/-13.6) ml vs. (70.5+/-20.0) ml, t=4.106,
      P=0.000], and the incision length was shorter [(3.9+/-0.9) cm vs. (6.7+/-1.3) cm,
      t=7.056, P=0.000] in the Overlap group. There were no significant differences in
      lymph nodes harvested (17.3+/-2.9 vs. 15.5+/-3.0), time to flatus [(2.8+/-1.3)
      days vs. (2.6+/-1.0)days], postoperative complications [6.2%(1/16) vs.
      9.5%(2/21)] and postoperative hospitalization [(4.6+/-1.4) days vs.(4.7+/-1.2)
      days] between the two groups (all P>0.05). CONCLUSION: The Overlap reconstruction
      method in totally laparoscopic left colectomy is a safe and feasible procedure,
      and provides less injury and better cosmetic outcome of abdominal wall.

PMID- 29577219
TI  - [Curative resection with minilaparotomy approach in the treatment of rectal
      cancer].
AB  - OBJECTIVE: To compare the surgical safety and short-term efficacy of
      minilaparotomy and laparoscopic approach for curative resection of rectal cancer.
      METHODS: The retrospective cohort study was adopted. A review of patients
      scheduled to undergo a curative resection of rectal cancer via minilaparotomy or
      laparoscopic approach at Department of Colorectal Surgery of Changhai Hospital
      from June 2016 to May 2017 was carried out. All the patients were confirmed as
      rectal cancer by postoperative pathology. The following patients were excluded
      from the study: patients who had acute complete obstruction or perforation;
      patients underwent Miles or Hartmann procedure; patients who required an
      elongation of the skin incision in minilaparotomy or a conversion from
      laparoscopic to open surgery. Finally, 216 patients were enrolled in this study,
      of whom 143 were performed with minilaparotomy approach (minilaparotomy group)
      and 73 with laparoscopic approach (laparoscopic group) for curative resection of
      rectal cancer. For the minilaparotomy technique, a 7 cm longitudinal midline
      incision was made between the pubic symphysis and umbilicus; a wound retractor
      was applied to the edge of the wound; lymph node dissection around the inferior
      mesenteric and artery high ligation of inferior mesenteric artery were performed;
      by moving the minilaparotomy wound laterally and caudad or cephalad with the S
      shaped hook, cautious mobilization of the relevant segment of the bowel loop was
      performed; bowel anastomosis was achieved by using the double-stapled technique;
      the gap of the pelvic floor peritoneum and mesentery were routinely closed by the
      absorbable surgical suture in cases with middle and low position rectal cancer.
      The surgical safety, the condition of resuming and the morbidity of postoperative
      complication were compared between the two groups. RESULTS: There were 145 men
      and 71 women. Age ranged from 26 to 87 years, with of mean age of 61 years.
      According to the TNM stage grouping, there were 61 patients with stage I(, 62
      with stage II(, 85 with stage III(, and 8 with stage IIII( disease, respectively.
      These two groups did not differ significantly in terms of age, sex, body mass
      index, site of tumor, TNM stage(all P>0.05). All the patients completed the
      operation successfully. The median operation time of minilaparotomy group was
      significantly shorter than that of laparoscopic group [164(80-296) minutes vs.
      230(90-665) minutes, Z=4.410, P=0.000]. The intraoperative medical consumable
      expense [11000(7000-22000) yuan vs. 23000(12000-47000) yuan, Z=11.759, P=0.000]
      and the total hospitalization expense [44000(22000-146000) yuan vs. 57000(45000
      126000) yuan, Z=9.637, P=0.000] were significantly lower in the minilaparotomy
      group. There were no significant differences between the two groups in terms of
      operative blood loss, number of harvested lymph nodes, distance of distal
      resection margin, positive rate of circumferential resection margin (all P>0.05).
      The rate of postoperative complication in minilaparotomy group was 7.0%(10/143)
      and in laparoscopic group was 9.6%(7/73) without significant difference
      (chi2=0.449, P=0.503). There were 2 patients in each group who required
      readmission to the hospital within postoperative 30 days. The cause of
      readmission was ileus or acute hyponatremia in minilaparotomy group, and ileus or
      pevic infection in laparoscopic group. One patient died of brain death caused by
      acute pulmonary embolism during the perioperative period in minilaparotomy group.
      CONCLUSIONS: The minilaparotomy approach for curative resection of rectal cancer
      is safe and feasible. As compared with laparoscopic approach, it is advantageous
      to achieve minimal invasiveness and early recovery, but much cheaper and less
      time consuming.

PMID- 29577220
TI  - [Comparison of the safety and the costs between laparoscopic assisted or totally
      laparoscopic uncut Roux-en-Y and BillrothII(+Braun reconstruction--a single
      center prospective cohort study].
AB  - OBJECTIVE: To compare the short-term safety and costs between laparoscopic
      assisted or totally laparoscopic uncut Roux-en-Y and Billroth II((BII() + Braun
      reconstruction after radical gastrectomy of distal gastric cancer. METHODS:
      Clinical data from our prospective database of radical gastrectomy were
      systematically analyzed. The patients who underwent laparoscopic gastrectomy with
      uncut Roux-en-Y or BII(+ Braun reconstruction between March 1st, 2015 and June
      30th, 2017 were screened out for further analysis. Both the reconstructions were
      completed by linear staplers. Uncut Roux-en-Y reconstruction was performed with a
      45 mm no-knife linear stapler (ATS45NK) on the afferent loop below the
      gastrojejunostomy. Continuous variables were compared using independent samples t
      test or Mann-Whitney U. The frequencies of categorical variables were compared
      using Chi-squared or Fisher exact test. RESULTS: Eighty-one patients were in
      uncut Roux-en-Y group and 58 patients were in BII(+Braun group. There were no
      significant differences between uncut Roux-en-Y group and BII(+Braun group in
      median age (56.0 years vs. 56.5 years, P=0.757), gender (male/female, 52/29 vs.
      46/12, P=0.054), history of abdominal surgery (yes/no, 10/71 vs. 4/54, P=0.293),
      neoadjuvant chemotherapy (yes/no, 21/60 vs. 11/47, P=0.336), BMI
      (thin/normal/overweight/obesity, 2/49/26/3 vs. 3/39/14/2, P=0.591), NRS 2002
      score (1/2/3/4, 58/15/5/3 vs. 47/5/3/3, P=0.403), pathological stage
      (0/I(/II(/III(, 3/41/20/17 vs. 1/28/13/16, P=0.755), median tumor diameter in
      long axis (2.5 cm vs. 3.0 cm, P=0.278), median tumor diameter in short axis (2.0
      cm vs. 2.0 cm, P=0.126) and some other clinical and pathological characteristics.
      There were no significant differences between uncut Roux-en-Y group and
      BII(+Braun group in morbidity of postoperative complication more severe than
      grade I([12.3% (10/81) vs. 17.2% (10/58), P=0.417], morbidity of anastomotic
      complication [1.2%(1/81) vs. 0, P=1.000] or hospitalization costs [(94000+/
      14000) yuan vs.(95000+/-16000) yuan, P=0.895]. The median first time to liquid
      diet (57.1 hours vs. 70.8 hours, P=0.017) and median postoperative hospital stay
      (9 days vs. 11 days, P=0.003) of the patients in uncut Roux-en-Y group were
      shorter than those in BII(+Braun group. CONCLUSION: Laparoscopic assisted or
      totally laparoscopic uncut Roux-en-Y reconstruction after radical gastrectomy of
      distal gastric cancer is safe and feasible with better recovery than BII(+Braun
      reconstruction.

PMID- 29577221
TI  - [Application of robotic and laparoscopic radical total gastrectomy to gastric
      cancer patients with body mass index >=24 kg/m2].
AB  - OBJECTIVE: To compare the short-term outcomes between robotic and laparoscopic
      radical total gastrectomy in gastric cancer patients with BMI index >=24 kg/m2.
      METHOD: Clinical data of 93 gastric cancer patients who underwent robotic and
      laparoscopic radical total gastrectomy at PLA General Hospital from April 2016 to
      April 2017 were retrospectively analyzed. The retrospective cohort study was
      adopted. INCLUSION CRITERIA: preoperatively definite diagnosis of primary gastric
      cancer by endoscopy and biopsy; preoperative BMI >=24 kg/m2; no previous
      abdominal surgery; no previous chemotherapy and radiotherapy; no distant
      metastasis or invasion into adjacent organs before operation or during operation;
      receiving radical gastrectomy; Roux-en-Y reconstruction of digestive tract in
      open procedure. According to approaches of minimally invasive surgery, 24
      patients underwent robotic surgery and 69 underwent laparoscopic surgery. The
      intraoperative parameters (overall operative time, pneumoperitoneal time, open
      procedure time, intraoperative blood loss, transfusion rate, number of total
      retrieved lymph nodes and metastatic lymph nodes) and postoperative parameters
      (drainage in the first postoperative day, the first defecation time, morbidity of
      postoperative complication and hospital stay) were compared between two groups.
      Correlation of the above parameters were analyzed. RESULTS: Of 93 patients, 77
      were male and 16 female with an average age of (60.0+/-10.6) years. The average
      BMI was (26.8+/-1.3) kg/m2 in whole patients, (26.9+/-1.6) kg/m2 in robotic group
      and (26.8+/-1.7) kg/m2 in laparoscopic group. No significant differences in age,
      gender, BMI, preoperative ASA class, postoperative pathological findings and
      clinical classification were observed between two groups, which made short-term
      parameters between two groups comparable. The robotic group had a significantly
      longer overall operative time [(301.2+/-68.9) minutes vs. (247.3+/-59.6) minutes,
      P=0.000], longer open procedure time [(141.5+/-26.3) minutes vs. (92.5+/-36.7)
      minutes, P=0.029] and higher cost than laparoscopy group[(17.5*104 +/- 9.7*104)
      yuan vs. (10.0*104 +/- 2.3*104) yuan, P=0.001]. Pneumoperitoneal operative time,
      intraoperative blood loss, transfusion rate, number of total retrieved lymph
      nodes, number of harvested metastatic lymph nodes and postoperative short-term
      efficacy were similar between the two groups (all P>0.05). In robotic group,
      pneumoperitoneal operative time was positively correlated with overall operative
      time (r=0.708, P=0.010); total cost was positively correlated with postoperative
      hospital stay (r=0.493, P=0.000) and open procedure time was negatively
      correlated with the first defecation time (r=-0.962, P=0.038). In laparoscopy
      group, total cost was positively correlated with overall operative time (r=0.411,
      P=0.046), drainage volume in the first postoperative day was positively
      correlated with the number of total dissected lymph node (r=0.540, P=0.006),
      postoperative hospital stay was positively correlated with intraoperative blood
      loss (r=0.574, P=0.003), total cost was positively correlated with intraoperative
      blood loss and hospital stay (r=0.609, P=0.002; r=0.865, P=0.000), drainage
      volume in the first postoperative day was positively correlated with BMI
      (r=0.533, P=0.007). CONCLUSION: For gastric cancer patients with BMI >=24 kg/m2,
      robotic radical total gastrectomy is associated with longer operative time and
      higher cost, but is less vulnerable to the change of BMI and more in favor of the
      realization of enhanced recovery after surgery (ERAS) than laparoscopic radical
      total gastectomy.

PMID- 29577222
TI  - [Establishment of comprehensive prediction model of acute gastrointestinal injury
      classification of critically ill patients].
AB  - OBJECTIVE: To develop the comprehensive prediction model of acute
      gastrointestinal injury (AGI) grades of critically ill patients. METHODS: From
      April 2015 to November 2015, the binary channel gastrointestinal sounds (GIS)
      monitor system which has been developed and verified by the research group was
      used to gather and analyze the GIS of 60 consecutive critically ill patients who
      were admitted in Critical Care Medicine of Chinese PLA General Hospital. Also,
      the AGI grades (Grande I(-IIII(, the higher the level, the heavier the
      gastrointestinal dysfunction) were evaluated. Meanwhile, the clinical data and
      physiological and biochemical indexes of included patients were collected and
      recorded daily, including illness severity score (APACHE II( score, consisting of
      the acute physiology score, age grade and chronic health evaluation), sequential
      organ failure assessment (SOFA score, including respiration, coagulation, liver,
      cardioascular, central nervous system and kidney) and Glasgow coma scale (GCS);
      body mass index, blood lactate and glucose, and treatment details (including
      mechanical ventilation, sedatives, vasoactive drugs, enteral nutrition, etc.)
      Then principal component analysis was performed on the significantly correlated
      GIS (five indexes of gastrointestinal sounds were found to be negatively
      correlated with AGI grades, which included the number, percentage of time, mean
      power, maximum power and maximum time of GIS wave from the channel located at the
      stomach) and clinical factors after standardization. The top 5 post-normalized
      main components were selected for back-propagation (BP) neural network training,
      to establish comprehensive AGI grades models of critically ill patients based on
      the neural network model. RESULTS: The 60 patients aged 19 to 98 (mean 54.6)
      years and included 42 males (70.0%). There were 22 cases of multiple fractures,
      15 cases of severe infection, 7 cases of cervical vertebral fracture, 7 cases of
      aortic repair, 5 cases of post-toxicosis and 4 cases of cerebral trauma. There
      were 33 emergency operation, 10 cases of elecoperectomy and 17 cases of drug
      treatment. There were 56 cases of diabetes(93.3%). Forty-five cases (75.0%) used
      vasoactive drugs, 37 cases (61.7%) used mechanical ventilation and 44 cases
      (73.3%) used enteral nutrition. APACHE II( score were 4.0 to 28.0(average 16.8)
      points. Four clinical factors were significantly positively related with AGI
      grades, including lactic acid level (r=0.215, P=0.000), SOFA score (r=0.383,
      P=0.000), the use of vascular active drugs (r=0.611, P=0.000) and mechanical
      ventilation (r=0.142, P=0.014). In addition to the five indexes of gastric bowel
      sounds which were found to be negatively correlated with AGI grades, the
      characteristics of 333 by 9 were composed of these nine indexes with high
      correlation of AGI grades. Five main components were selected after principal
      component analysis of these nine correlated indexes. A comprehensive AGI grades
      model of critically ill patients with a fitting degree of 0.967 3 and an accuracy
      rate of 82.61% was built by BP artificial neural network. CONCLUSION: The
      comprehensive model to classify AGI grades with the GIS is developed, which can
      help further predicting the classification of AGI grades of critically ill
      patients.

PMID- 29577223
TI  - [Effect of neoadjuvant chemotherapy on nutritional status of locally advanced
      gastric cancer].
AB  - OBJECTIVE: To study the effect of neoadjuvant chemotherapy on nutritional status
      in patients with locally advanced gastric cancer. METHODS: Cases inclusion
      criteria: (1)18-65 years old; (2) Gastric cancer confirmed by gastroscopic
      biopsy; (3) Preoperative TNM stage III( according to the AJCC stage 2000
      standard; (4) Kamosfsky functional status score> 60 points; (5)Receiving
      neoadjuvant chemotherapy voluntarily and signing the informed consent form. Case
      exclusion criteria: (1)Having contraindications of chemotherapy and surgery; (2)
      Suffering from heart, liver and kidney and other underlying diseases; (3)
      Concurrent with malignant diseases, wasting disease or other digestive diseases.
      According to the above criteria, clinical data of 73 patients of stage III(
      gastric cancer receiving neoadjuvant chemotherapy at Weifang People's Hospital
      from May 2015 to March 2017 were prospectively collected. The cohort study was
      adopted. After removing 3 patients who did not complete the chemotherapy, a total
      of 70 patients who completed the chemotherapy were included in the study. All the
      patients received SOX chemotherapy without nutritional support during
      chemotherapy. Changes of body composition and nutritional indicators were
      analyzed before and after chemotherapy, and according to the tumor regression
      after chemotherapy, patients were divided into response group (complete or sub
      total tumor regression) and non-response group (tumor part, with or without a
      small amount of retreat) for stratified analysis. RESULTS: Of 70 gastric cancer
      patients, 40 were male and 30 were female with a age of (53.8+/-6.4) (28 to 64)
      years. There were 26 cases (37.1%) of stage III(a, 35 cases (50.0%) of stage
      III(b and 9 cases (12.9%) of stage III(c. There were 41 cases in response group
      and 29 cases in non-response group. Three patients (4.3%) were complete remission
      (CR) and 38 patients (54.3%) were partial remission (PR) in response group, while
      23 cases (32.9%) were stable disease (SD) and 6 cases (8.6%) were progressive
      disease (PD). After neoadjuvant chemotherapy, the extracellular fluid of the
      whole patients increased from (13.3+/-1.7) L to (13.5+/-1.6) L (t=-2.044,
      P=0.045); the intracellular fluid decreased from (21.4+/-2.5) L to (21.1+/-2.4) L
      (t=2.369, P=0.021); the lymphocyte count decreased from (0.31+/-0.10)*109/L to
      (0.29+/-0.10)*109/L (t=1.706, P=0.009); the other indexes were not significantly
      different (all P>0.05). Stratified analysis showed that after neoadjuvant
      chemotherapy in response group, body mass increased from (60.1+/-8.8) kg to
      (61.0+/-8.3) kg (t=-2.773, P=0.008); body mass index increased from (21.9+/-2.4)
      kg/m2 to (22.3+/-1.9) kg/m2(t=-3.479, P=0.001), while above two parameters did
      not differ significantly in non-response group. No significant differences in
      body mass, body mass index, skeletal muscle, inorganic salt, extracellular fluid,
      body fat, protein, upper arm circumference and intracellular fluid were found
      between two groups before and after neoadjuvant chemotherapy(all P>0.05). Except
      slight decrease in hemoglobin and lymphocyte, the other nutritional indicators
      were slightly elevated in response group, while the differences were not
      statistically significant(all P>0.05). All nutritional indicators in non-response
      group were slightly decreased without significant differences as well (all
      P>0.05). CONCLUSION: Neoadjuvant chemotherapy does not aggravate malnutrition in
      patients with locally advanced gastric cancer.

PMID- 29577224
TI  - [Relationship between the expression of DDX39 protein and prognosis of colorectal
      cancer].
AB  - OBJECTIVE: To investigate the relationship between the expression of DDX39
      protein and prognosis in colorectal cancer. METHODS: Clinical data and paraffin
      specimens of postoperative tumor tissue from 824 patients with primary colorectal
      cancer who received first surgical treatment at the Department of Colorectal
      Surgery of Changhai Hospital of Navy Military Medical University from January
      2010 to December 2011 were collected. Paraffin samples of paracancerous tissues
      of 38 patients were served as controls. At the same time, samples of normal
      rectal mucous membrane from 37 cases after procedure of prolapse and hemorrhoids,
      and samples of colorectal adenoma from 33 cases after endoscopic treatment were
      enrolled in this study. All the specimens were made as the tissue microarray, and
      the expression of DDX39 protein was detected by immunohistochemistry. The
      expression of DDX39 in the epithelium and stroma was evaluated with the average
      staining intensity (H-Score) and the number of positive cells. It was defined as
      high expression in the epithelium that the H-Score was greater than or equal to
      200. It was defined as high expression in the stroma that the number of positive
      cells was greater than or equal to 50 in 200 times the field of vision.
      Relationship of different DDX39 expression levels with clinicopathological
      parameters and prognosis of colorectal cancer was analyzed. RESULTS: The
      expression of DDX39 in colorectal cancer tissues was lower than that in normal
      tissues, paracancerous tissues and adenomatous tissues, whether it is in the
      epithelium or in the stroma [DDX39 expression in the epithelium: normal tissues
      253.2+/-64.1, paracancerous tissues 238.8+/-79.2, adenomatous tissues 259.4+/
      51.6, colorectal cancer tissues 194.2+/-76.5 (P=0.000, P=0.005, P=0.000,
      respectively); DDX39 expression in the stroma: normal tissues 110.1+/-64.8,
      paracancerous tissues 106.0+/-49.2, adenomatous tissues 108.5+/-79.1, colorectal
      cancer tissues 54.1+/-34.7(all P=0.000)]. Among the cases of colorectal cancer,
      there were 541 cases of high DDX39 expression and 283 cases of low DDX39
      expression in the epithelium; there were 424 cases of high DDX39 expression of
      and 400 cases of low DDX39 expression in the stroma. The high DDX39 expression
      and low DDX39 expression in epithelial and stromal of colorectal cancer were
      related respectively with tumor location (P=0.006, P=0.016), degree of tumor
      differentiation (P=0.002, P=0.064), TNM stage (P=0.021, P=0.000), serum CEA level
      (P=0.003, P=0.005), serum CA199 level (P=0.040, P=0.005) and tumor recurrence and
      metastasis (P=0.000, P=0.000). All the colorectal cancer cases were followed up
      for (41.6+/-15.7) months after operation. The 5-year overall survival (OS) and
      disease-free survival (DFS) rates of the cases with epithelial low DDX39
      expression were 84.1% and 61.5%, and both were significantly lower as compared to
      those with epithelial high DDX39 expression (95.4% and 88.2%, P=0.000, P=0.000).
      The 5-year OS and DFS rates of the stroma low DDX39 expression were 86.8% and
      66.8%, and both were significantly lower as compared to those with stroma high
      DDX39 expression (96.1% and 90.6%, P=0.000, P=0.000). Cox multivariate analysis
      showed that tumor differentiation (OS:HR=0.252, 95%CI: 0.128 to 0.497, P=0.000;
      DFS:HR=0.266, 95%CI: 0.134 to 0.530, P=0.000), DDX39 expression level in
      epithelium (OS: HR =0.229, 95%CI: 0.138 to 0.382, P=0.000; DFS: HR =0.266, 95%CI:
      0.158 to 0.446, P=0.000), and DDX39 expression level in stroma (OS: HR =0.331,
      95%CI: 0.188 to 0.582, P=0.000; DFS:HR=0.326, 95%CI: 0.184 to 0.578, P=0.000)
      were independent influencing factors of overall or disease-free survival in
      patients with colorectal cancer. CONCLUSION: The low expression of DDX39 protein
      suggests poor prognosis and DDX39 is expected to be a new prognostic marker of
      colorectal cancer.

PMID- 29577225
TI  - [Progress in the treatment of surgical procedures for slow transit constipation].
AB  - Slow transit constipation (STC) is the most common type of chronic constipation,
      and surgical treatment is one of the most important means for the treatment of
      slow transit constipation. With the introduction of the concept of STC and the
      normalization of STC treatment, development of surgical treatment in slow transit
      constipation is continuous, and the innovation of the operation method in slow
      transit constipation is continuous as well from partial colectomy, total
      colectomy (including ileorectal anastomosis, anorectal anastomosis and ileum bag
      anal canal anastomosis) to subtotal colectomy (including ileosigmoid colon
      anastomosis, isoperistaltic cecum rectal anastomosis and antiperistaltic cecum
      rectal anastomosis). Among these procedures, total colectomy ileorectal
      anastomosis is the ideal surgical procedure for the treatment of STC. Recent
      studies revealed that subtotal colectomy cecum rectal anastomosis could also
      achieve good efficacy. In addition, the other procedures for the treatment of STC
      include ileostomy, anterograde colonic lavage and colon exclusion, but it is
      necessary to strictly grasp the indications. With the development of minimally
      invasive technology, the application of laparoscopic technology in STC has been
      emphasized gradually. In general, the operation method has experienced from
      simple to complex and individual choice; from single surgical approach to
      multiple surgical methods; from abdominal open surgery to laparoscopic minimally
      invasive surgery. Relieving constipation symptoms and reducing the incidence of
      complications is the goal of surgical treatment that has always been the pursuit
      of STC surgery. The surgical method with good efficacy, small trauma, quick
      recovery and less complications must be designed to meet the individualized needs
      of patients with different constipations. In this paper, the efficacy and
      progress of surgical treatment of slow transit constipation from the generation
      and development are reviewed.

PMID- 29577226
TI  - Neuronal nitric oxide synthase phosphorylation induced by docosahexaenoic acid
      protects dopaminergic neurons in an experimental model of Parkinson's disease.
AB  - INTRODUCTION: Docosahexaenoic acid (DHA) has been shown to have beneficial
      effects on Parkinson's disease (PD). The aim of this study was to investigate if
      the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal
      nitric oxide synthase (nNOS) in an experimental mouse model of PD. MATERIAL AND
      METHODS: An experimental model of PD was created by intraperitoneal injections (4
      * 20 mg/kg) of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine
      (MPTP). Three-month-old male C57BL/6 mice were randomly divided into four groups
      as follows: control (C), DHA-treated (DHA), MPTP-injected (MPTP) and DHA-treated
      and MPTP-injected (DHA + MPTP). DHA (36 mg/kg/day) was administered daily by
      gavage for four weeks. Motor activity of the mice was evaluated with pole,
      locomotor activity and rotarod tests. Caspase-3 activity, nitrate/nitrite and 4
      hydroxynonenal (4-HNE) levels were determined by spectrophotometric assays.
      Immunohistochemistry was used to localize and assess the expressions of tyrosine
      hydroxylase (TH), nNOS and phospho-nNOS (p-nNOS) in SN. RESULTS: An increased
      return and total down time in the MPTP group was observed in the pole test, while
      DHA treatment decreased both parameters. The ambulatory activity, total distance
      and total locomotor activities were decreased in the MPTP group, whereas they
      were increased by DHA treatment. MPTP-treated animals exhibited shorter time on
      the rod test which was significantly increased by DHA treatment. DHA
      administration significantly decreased 4-HNE and nitrate/nitrite levels of SN
      supernatants and protected the TH (+) dopaminergic neurons of SN in the DHA +
      MPTP group compared to the MPTP group. DHA treatment significantly decreased nNOS
      and increased p-nNOS immunoreactivities in the DHA + MPTP group compared to the
      MPTP group. CONCLUSIONS: These results indicate that DHA treatment protects
      dopaminergic neurons in SN via increasing nNOS serine 852 phosphorylation in the
      experimental mice model of PD.

PMID- 29577228
TI  - Large pragmatic randomised controlled trials in peri-operative decision making:
      are they really the gold standard?

PMID- 29577227
TI  - Pathological study of pulmonary toxicity induced by intratracheally instilled
      Asian sand dust (Kosa): effects of lowered serum zinc level on the toxicity.
AB  - : I: NTRODUCTION: We have previously reported that Asian sand dust (ASD) induced
      acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported
      to influence inflammation and wound healing. The purpose of the study was to
      assess the effects of lowered serum Zn levels on the lung toxicity induced by
      ASD. MATERIAL AND METHODS: Mice that were fed diets containing normal (group 1)
      or low (group 2) content of Zn for 8 weeks were intratracheally instilled with
      3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months
      after instillation. Paraffin sections of lung tissues were stained by hematoxylin
      and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and
      interleukin (IL)-1beta as well as inflammasome (NALP3), autophagy (LC-3) and
      lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by
      electron microscopy. RESULTS: Following histological examination of the lung,
      similar patterns of inflammatory changes were observed in mice with normal and
      low serum Zn concentrations; however, they were more prominent and persistent in
      mice with low serum Zn level. These changes were both purulent (acute) and
      pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the
      changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages
      (Mo) were clearly visible. The macrophages expressed TNF and IL-1beta, and semi
      quantitative analysis revealed a larger number of TNF-positive Mo in mice with
      normal level of serum Zn and a larger number of IL-1beta-positive Mo in mice with
      low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes
      containing ASD particles were observed in the cytoplasm of Mo in mice with low
      serum Zn concentration. CONCLUSIONS: These findings suggest that low serum zinc
      concentration may induce the modulation of cytokine expression and lysosomal
      malfunction by phagocytotic and/or autophagic mechanisms, and may result in
      interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD.

PMID- 29577229
TI  - Comparison of guidelines for the treatment of unipolar depression: a focus on
      pharmacotherapy and neurostimulation.
AB  - OBJECTIVE: To determine the level of agreement across a set of evidence-based
      guidelines for management of the unipolar depressive disorders and with a focus
      on physical treatments. METHOD: A literature search was undertaken using the
      terms 'depression', 'depressive' and 'guidelines', using PubMed, Cochrane
      Database of Systematic Reviews and the National Guideline Clearinghouse. Twelve
      national psychiatric or professional guideline-producing organizations were
      identified from the period 2007-2017, with guidelines qualitatively reviewed by
      two assessors. RESULTS: For major depressive disorder (MDD), there was general
      consensus to use an antidepressant (AD) in cases of greater severity, although
      disagreement on AD use in mild to moderate depression. There was some agreement
      on choice of AD class in first-line treatment recommendations, though great
      variability in second- and third-line management particularly in recommended
      augmentation and combined AD strategies. Electroconvulsive therapy was considered
      in all but one guideline, with other neurostimulation treatments being less
      consistently covered and with variable recommendations. Finally, there was low
      consistency in the management of dysthymia, persistent depressive disorder and
      treatment resistant depression. CONCLUSION: Our review identifies varying levels
      of consistency in guideline recommendations. Strategies to improve reliability in
      guideline formulation should also improve their validity.

PMID- 29577230
TI  - Neutron-based computed microtomography: Pliobates cataloniae and Barberapithecus
      huerzeleri as a test-case study.
AB  - OBJECTIVES: High-resolution imaging of fossils with X-ray computed
      microtomography (MUCT) has become a very powerful tool in paleontological
      research. However, fossilized bone, embedding matrix, and dental tissues do not
      always provide a distinct structural signal with X-rays. We demonstrate the
      benefits of high-resolution neutron radiation in three different specimens
      showing problematic contrasts with X-ray MUCT. MATERIALS AND METHODS: We compare
      neutron with X-ray MUCT scans of fossils from two Miocene catarrhines from the
      Valles-Penedes Basin: the cranium (IPS58443.1, holotype) of the putative stem
      hominoid Pliobates cataloniae, to discriminate between bone and matrix; and two
      lower molars (IPS1724n,o, holotype) of Barberapithecus huerzeleri, to
      discriminate among dental tissues. RESULTS: X-ray MUCT scans of these specimens
      fail to retrieve any contrast between matrix/bone and enamel/dentine, whereas
      neutron MUCT scans deliver high-contrast images, enabling a proper evaluation of
      the specimens' internal anatomy. DISCUSSION: Low bone/matrix intensity difference
      with X-ray MUCT scans in IPS58443.1 is due to the extreme similarity in chemical
      composition between the matrix and the fossilized tissues, and the presence of
      high-density elements. In IPS1724, it is attributable to the convergence of
      enamel and dentine compositions during fossilization. On the contrary, neutron
      radiation returns very different contrasts for different isotopes of the same
      element and easily penetrates most metals. Neutron-based MUCT scans therefore
      enable a correct definition of the bone/sediment and enamel/dentine interfaces,
      and hence a better segmentation of the images stack. We conclude that neutron
      radiation represents a successful alternative for high-resolution uCT of small
      sized fossils that are problematic with X-rays.

PMID- 29577232
TI  - Before and after studies and historical controls. Is the proof in the pudding?

PMID- 29577231
TI  - Morphological variation in the genus Chlorocebus: Ecogeographic and
      anthropogenically mediated variation in body mass, postcranial morphology, and
      growth.
AB  - OBJECTIVES: Direct comparative work in morphology and growth on widely dispersed
      wild primate taxa is rarely accomplished, yet critical to understanding
      ecogeographic variation, plastic local variation in response to human impacts,
      and variation in patterns of growth and sexual dimorphism. We investigated
      population variation in morphology and growth in response to geographic variables
      (i.e., latitude, altitude), climatic variables (i.e., temperature and rainfall),
      and human impacts in the vervet monkey (Chlorocebus spp.). METHODS: We trapped
      over 1,600 wild vervets from across Sub-Saharan Africa and the Caribbean, and
      compared measurements of body mass, body length, and relative thigh, leg, and
      foot length in four well-represented geographic samples: Ethiopia, Kenya, South
      Africa, and St. Kitts & Nevis. RESULTS: We found significant variation in body
      mass and length consistent with Bergmann's Rule in adult females, and in adult
      males when excluding the St. Kitts & Nevis population, which was more sexually
      dimorphic. Contrary to Rensch's Rule, although the South African population had
      the largest average body size, it was the least dimorphic. There was significant,
      although very small, variation in all limb segments in support for Allen's Rule.
      Females in high human impact areas were heavier than those with moderate
      exposures, while those in low human impact areas were lighter; human impacts had
      no effect on males. CONCLUSIONS: Vervet monkeys appear to have adapted to local
      climate as predicted by Bergmann's and, less consistently, Allen's Rule, while
      also responding in predicted ways to human impacts. To better understand
      deviations from predicted patterns will require further comparative work in
      vervets.

PMID- 29577233
TI  - An assessment of the tolerability of the Cook staged extubation wire in patients
      with known or suspected difficult airways extubated in intensive care.
AB  - The Cook staged extubation set (Cook Medical) has been developed to facilitate
      management of the difficult airway. A guidewire inserted before tracheal
      extubation provides access to the subglottic airway should re-intubation be
      required. This prospective cohort study examines patients' tolerance of the
      guidewire and its impact on clinical status around tracheal extubation in the
      intensive care unit. Vital signs, incidence of symptoms and patient tolerance of
      the wire were recorded. Twenty-three patients were enrolled and 17 (73%)
      tolerated the wire for 4 h. Nasendoscopy was performed in 11 of these patients
      and revealed one wire was in the oesophagus. The most common symptom was a mild
      intermittent cough in 13 patients. There was no impact of the guidewire on
      nursing care in 16 patients, tolerable impact in five and severe impact
      necessitating removal of the wire in one patient.

PMID- 29577235
TI  - Pragmatic trials in peri-operative medicine: why, when and how?

PMID- 29577234
TI  - Physical Resilience: Not Simply the Opposite of Frailty.

PMID- 29577236
TI  - Recurrence and chronicity of major depressive disorder and their risk indicators
      in a population cohort.
AB  - OBJECTIVE: The naturalistic course of major depressive disorder (MDD) and risk
      indicators for recurrence and chronicity are best studied using a population
      sample without clear selection bias. However, such studies are scarce. This
      limits clinical decision-making concerning monitoring and maintenance treatment.
      METHOD: Data were used from the Netherlands Mental Health Survey and Incidence
      Study-2, a psychiatric epidemiological cohort study among a representative adult
      population. Two groups at baseline were selected to study recurrence and
      chronicity of MDD at follow-up. Diagnoses were assessed with the Composite
      International Diagnostic Interview 3.0. RESULTS: Among remitted MDD cases (n =
      746), the cumulative recurrence rate was 4.3% at 5 years, 13.4% at 10 years and
      27.1% at 20 years. Time to recurrence was predicted by vulnerability
      characteristics (childhood abuse, negative life events, parental
      psychopathology), physical health, functioning, clinical characteristics of
      depression (previous episodes, severity, medication use), psychiatric comorbidity
      and mental health use. Among current MDD cases (n = 242), 12% developed a chronic
      depressive episode over 6 years. Chronic course was predicted by similar risk
      indicators as recurrence, except for vulnerability characteristics and physical
      health. CONCLUSION: These risk indicators may help to identify patients requiring
      monitoring and who could benefit from preventive interventions or maintenance
      treatment.

PMID- 29577237
TI  - Two-stage surgical repair in 31 patients with stage II-III hidradenitis
      suppurativa.

PMID- 29577238
TI  - Stress ulcer prophylaxis in adult intensive care unit patients - a protocol for a
      systematic review.
AB  - BACKGROUND: In the intensive care unit (ICU), stress ulcer prophylaxis with
      proton pump inhibitors or histamine-2-receptor antagonists is standard of care
      although gastrointestinal bleeding remains uncommon. It remains unknown whether
      its use is associated with benefits or harms and the quality of evidence
      supporting the use of stress ulcer prophylaxis has been questioned. Accordingly,
      the objective of this systematic review was to critically assess the evidence
      from randomized clinical trials on the benefits and harms of stress ulcer
      prophylaxis vs. placebo or no prophylaxis in adult ICU patients. METHODS: We will
      systematically search for randomized clinical trials in major international
      databases. Two authors will independently screen and select trials for inclusion,
      extract data and assess the methodological quality using the Cochrane risk of
      bias tool. Any disagreement will be resolved by consensus. We will perform
      conventional meta-analyses using Review Manager, and STATA 15, and we will assess
      the risk of random errors using Trial Sequential Analysis. Also, we will assess
      and report the overall quality of evidence for all outcomes according to GRADE.
      DISCUSSION: The evidence on the benefits and harms of stress ulcer prophylaxis in
      adult ICU patients is unclear and an updated systematic review is warranted as
      new trials have been published. To control risks of systematic and random errors,
      we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our
      ambition with this systematic review is to provide updated, reliable and precise
      data to better inform decision makers on the use of stress ulcer prophylaxis in
      adult ICU patients.

PMID- 29577239
TI  - An atypical clinical presentation of lichen planus pigmentosus with typical
      dermoscopic pattern.
AB  - We report a rare and interesting case of a combined linear, Blaschkoid and
      zosteriform pattern of lichen planus pigmentosus. Dermoscopy showed discrete
      bluish-grey dots, globules, blotches and rods against a brownish background. A
      skin biopsy confirmed the diagnosis from the presence of civatte bodies, melanin
      incontinence and band-like inflammation.

PMID- 29577240
TI  - Age cannot wither her? - NCEPOD at 30.

PMID- 29577241
TI  - Detection of human papillomavirus 42 in a squamous cell carcinoma.

PMID- 29577242
TI  - Airway management in critical illness: practice implications of new Difficult
      Airway Society guidelines.

PMID- 29577243
TI  - Pain after vaginal prolapse repair surgery with mesh is a post-surgical
      neuropathy which needs to be treated - and can possibly be prevented in some
      cases.
AB  - Post-surgical neuropathy leading to chronic pain is a recognised complication. It
      also can occur after surgery for pelvic organ prolapse repair involving mesh.
      Post-surgical neuropathy needs to be identified and properly treated to minimise
      the occurrence of chronic pain. A treatment algorithm is put forward for
      discussion .

PMID- 29577244
TI  - Treatment of scalp dysesthesia utilising simple exercises and stretches: A pilot
      study.
AB  - BACKGROUND/OBJECTIVES: Scalp dysesthesia is characterised by abnormal cutaneous
      sensations such as burning, stinging or itching of the scalp in the absence of
      objective dermatological findings. We hypothesised that the unpleasant sensations
      are the result of a sensory neuropathy secondary to cervical spine dysfunction
      and chronic tension of the pericranial muscles. The aim of this pilot study was
      to evaluate the use of an exercise protocol consisting of cervical spine range of
      movement exercises, gentle mobilisation and muscle stretches over 4 weeks. The
      exercise protocol was designed to relieve cervical nerve compression through the
      restoration of cervical homeostasis. METHODS: In total, 16 participants, aged 18
      71 (average 45 years), diagnosed with scalp dysesthesia were recruited from an
      outpatient dermatology clinic and given instructions on how to perform a
      specifically designed exercise protocol twice daily for 4 weeks. Baseline
      characteristics and a visual analogue scale (VAS) for pruritus were recorded
      prior to commencement and a VAS for pruritus recorded weekly thereafter. RESULTS:
      At week 4, 10 participants experienced a satisfactory reduction in their
      symptoms, four experienced complete resolution and two experienced no benefit,
      with no adverse effects reported. We conclude that a programme of simple
      exercises and stretches is an effective treatment for scalp dysesthesia.
      CONCLUSIONS: This low-risk treatment is easily implemented, non-invasive and non
      pharmacological. Within the limits of this small pilot study, benefits are shown,
      and we believe further research is warranted.

PMID- 29577245
TI  - Longitudinal Associations Among Child Maltreatment, Resting Frontal
      Electroencephalogram Asymmetry, and Adolescent Shyness.
AB  - Child maltreatment is linked to distinct neurophysiological patterns and social
      emotional vulnerability. Relations among maltreatment, relative resting frontal
      alpha asymmetry, shyness, and psychopathology were examined prospectively.
      Adolescent girls (age 14-16) who experienced child maltreatment (N = 55) were
      compared to nonmaltreated controls (N = 25), and returned for 6- and 12-month
      follow-ups. Among participants exhibiting relative right frontal asymmetry,
      maltreated adolescents reported higher shyness than controls at Time 1. Low
      stable and high-stable shyness trajectories were observed for maltreated
      participants. Compared to low shy, participants in high-shy trajectory reported
      at Time 3: higher neuroticism and generalized anxiety; and lower extraversion if
      they also exhibited relative right frontal asymmetry. Thus, right frontal brain
      activity and shyness are involved in social-emotional vulnerability of
      adolescents who experienced child maltreatment.

PMID- 29577246
TI  - Labels or Concepts? The Development of Semantic Networks in Bilingual Two-Year
      Olds.
AB  - The adult lexicon links concepts and labels with related meanings (e.g., dog
      cat). How do children's encounters with concepts versus labels contribute to
      semantic development? Three studies investigated semantic priming in 40
      monolinguals and 32 bilinguals, who have similar experience with concepts but
      different experience with labels (i.e., monolinguals hear "dog," bilinguals hear
      "dog" and "chien"). Similarities in performance across monolinguals and
      bilinguals at age 24 months, as well as across bilinguals' two languages at age
      30 months, support the position that encounters with concepts contribute more to
      early semantic development than encounters with labels. Findings also suggest
      that the effects of semantic priming are challenging to observe at 24 months but
      are strong in bilinguals by age 30 months.

PMID- 29577247
TI  - Accelerated barrier recovery and enhancement of the barrier integrity and
      properties by topical application of a pH 4 vs. a pH 5.8 water-in-oil emulsion in
      aged skin.
AB  - BACKGROUND: Increased skin-surface pH is an important host-related factor for
      deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether
      restoration of skin pH through topical application of a water-in-oil emulsion
      with pH 4 improved the barrier homeostasis in aged skin, and compared the effects
      with an identical galenic formulation with pH 5.8. METHODS: The effects of the
      test formulations on barrier recovery were investigated by repeated measurements
      of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone
      induced impairment of barrier function in aged skin. The long-term effects of the
      pH 4 and pH 5.8 emulsions were analysed by investigation of the barrier integrity
      and cohesion, the skin-surface pH and the skin roughness and scaliness before and
      after a 4-week, controlled application of the formulations. RESULTS: The
      application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h
      and 6 h after acetone-induced barrier disruption the differences in the TEWL
      recovery between the pH 4 treated and acetone control fields were significant.
      Furthermore, long-term application of the pH 4 formulation resulted in
      significantly decreased skin pH, enhanced barrier integrity and reduced skin
      surface roughness and scaliness. At the same time points, the pH 5.8 formulation
      exerted only minor effects on the barrier function parameters. CONCLUSIONS:
      Exogenous acidification through topical application of a water-in-oil emulsion
      with pH 4 leads to improvement of the skin barrier function and maintenance of
      the barrier homeostasis in aged skin.

PMID- 29577248
TI  - Behavioural repertoire of free-range laying hens indoors and outdoors, and in
      relation to distance from the shed.
AB  - BACKGROUND: Access to an outdoor area is believed to allow free-range hens to
      express a greater behavioural repertoire. However, very little research has been
      done in this area. We hypothesised that the type and frequency of behaviours
      would differ between areas that vary in their characteristics and distance from
      the shed. METHODS: This preliminary study investigated the behaviour of free
      range laying hens in indoor and outdoor areas on one commercial free-range farm,
      through video recordings and scan sampling of focal hens, with the aim of
      determining their behavioural repertoire and time budget. RESULTS: While ranging,
      hens spent most of their time foraging. Indoors, hens preened and rested.
      Behaviour in the wintergarden showed similarities to both the indoor and outdoor
      areas, with preening, resting and foraging behaviours. Differences were not in
      the main behavioural repertoire, but rather in terms of time budget, with access
      to the range and wintergarden encouraging exploration. CONCLUSION: There was no
      difference in the types of behaviours that hens performed in the outdoor range
      compared with inside the shed, but access to a wintergarden and the outdoor range
      were favoured by the hens for foraging.

PMID- 29577249
TI  - A survey of northern Victorian dairy farmers to investigate dairy calf
      management: colostrum feeding and management.
AB  - OBJECTIVES: To describe colostrum management practices carried out in northern
      Victorian dairy herds and to identify weaknesses in these areas that may affect
      calf health and welfare by comparing the results with the current industry
      recommendations METHODS: A questionnaire to obtain information about colostrum
      management and calf-rearing practices was sent to commercial dairy farming
      clients of Rochester Veterinary Practice between June and September 2013. The
      questionnaire consisted of a general herd overview and colostrum harvesting
      practices. RESULTS: The response rate was 39% (58/150). Many dairy producers were
      not meeting the current industry recommendations in the following areas: (1) time
      of removal calf from the dam, (2) relying on calf suckling colostrum from the dam
      to achieve adequate passive transfer, (3) failing to supplement calves with
      colostrum, (4) feeding inadequate volumes of colostrum, (5) delayed colostrum
      harvesting, (6) pooling of colostrum, (7) failing to objectively assess colostrum
      quality or relying on visual assessment and (8) storing colostrum for a prolonged
      periods of time at ambient temperatures. CONCLUSION: The results from this survey
      highlight the need for greater awareness of industry standards for colostrum
      management and feeding hygiene.

PMID- 29577251
TI  - Reproductive performance of cows after fixed-time artificial insemination with
      ovulation synchronisation and re-synchrony in southern Australian dairy herds.
AB  - OBJECTIVE: To describe reproductive performance of lactating dairy cows after
      fixed-time artificial insemination (FTAI) with ovulation synchronisation and re
      synchrony in Australian dairy herds, and to compare reproductive outcomes with
      those of conventional mating programs. METHODS: The study was conducted in two
      seasonally calving dairy herds in which lactating dairy cows (n = 675) were
      enrolled into three treatment groups: group 1, oestrus detection and AI for 34
      days followed by a natural service period; group 2, FTAI on day 1 followed by re
      synchrony of all cows prior to ultrasound pregnancy diagnosis at day 31 and FTAI
      of cows diagnosed not pregnant at day 34, then a natural service period; group 3,
      FTAI on day 1 followed by oestrus detection and AI for 34 days, then a natural
      service period. First-service conception rate (FSCR), 6-week in-calf (6WIC) rate
      and proportions pregnant at the end of mating were compared using logistic
      regression with farm fitted as a fixed effect. Times from mating start date to
      conception were described using survival analysis with Kaplan-Meier failure
      functions. RESULTS: FSCRs (45.3%, 49.1% and 45.6% for groups 1, 2 and 3,
      respectively) and proportions pregnant at the end of mating (77.6%, 76.0% and
      76.8% for groups 1, 2 and 3, respectively) were similar for all groups. The 6WIC
      rate in group 2 was similar to that in group 3 (70.4% vs. 67.2%; P = 0.486), but
      tended to be higher than in group 1 (70.4% vs. 62.0%, P = 0.066). The median days
      to pregnancy for cows that conceived was 1 day in groups 2 and 3 and 10 days in
      group 1. CONCLUSION: Mating plans that use FTAI with ovulation synchronisation
      and re-synchrony during the AI period can achieve comparable reproductive
      performance to conventional mating programs in seasonally calving dairy herds.

PMID- 29577252
TI  - A survey of northern Victorian dairy farmers to investigate dairy calf
      management: calf-rearing practices.
AB  - OBJECTIVES: To describe the calf-rearing practices carried out in northern
      Victorian dairy herds and to identify weaknesses that may affect calf health and
      welfare by comparing the results with current industry recommendations. METHODS:
      Survey of dairy farms from Rochester and the surrounding farming area. RESULTS:
      The response rate was 39% (58/150). Many dairy producers were not meeting the
      current industry recommendations in the following areas: (1) delayed access to
      pellets and roughage, (2) failing to provide access to water from birth, (3)
      delayed disbudding of calves, (4) delayed timing of booster vaccinations, (5)
      weaning based on age alone, (6) failing to isolate sick calves and (7) early sale
      age of excess calves. CONCLUSION: The results from this survey highlight the need
      for greater awareness of industry standards for calf husbandry and weaning.

PMID- 29577253
TI  - Antimicrobial susceptibility testing by Australian veterinary diagnostic
      laboratories.
AB  - BACKGROUND: The national strategy for tackling antimicrobial resistance
      highlights the need for antimicrobial stewardship in veterinary practice and for
      surveillance of antimicrobial susceptibility in veterinary pathogens. Diagnostic
      laboratories have an important role in facilitating both of these processes, but
      it is unclear whether data from veterinary diagnostic laboratories are similar
      enough to allow for compilation and if there is consistent promotion of
      appropriate antimicrobial use embedded in the approaches of different
      laboratories to susceptibility testing. METHODS: A cross-sectional study of
      antimicrobial susceptibility testing and reporting procedures by Australian
      veterinary diagnostic laboratories was conducted in 2017 using an online
      questionnaire. All 18 veterinary diagnostic laboratories in Australia completed
      the questionnaire. RESULTS: Kirby-Bauer disc diffusion was the method
      predominantly used for antimicrobial susceptibility testing and was used to
      evaluate 86% of all isolates, although two different protocols were used across
      the 18 laboratories (CLSI 15/18, CDS 3/18). Minimum inhibitory concentrations
      were never reported by 61% of laboratories. Common isolates were consistently
      reported on across all species, except for gram-negative isolates in pigs, for
      which there was some variation in the approach to reporting. There was
      considerable diversity in the panels of antimicrobials used for susceptibility
      testing on common isolates and no consistency was apparent between laboratories
      for any bacterial species. CONCLUSION: We recommend that nationally agreed and
      consistent antimicrobial panels for routine susceptibility testing should be
      developed and a uniform set of guidelines should be adopted by veterinary
      diagnostic laboratories in Australia.

PMID- 29577256
TI  - Corrigendum.

PMID- 29577254
TI  - Prevalence and risk factors for medical events following exercise at Australian
      Greyhound race meetings.
AB  - AIM: A prospective, observational study to determine the prevalence of post
      exercise conditions at Australian Greyhound race meetings and to assess
      association with race performance and other environmental, race- and dog-related
      factors was undertaken. METHODS: A total of 4020 starters were observed (2813
      Greyhounds, 1009 trainers, 536 races, 52 race meets, 48 race dates and 11 race
      tracks) following a race. The presence of diaphragmatic flutter (DF), ataxia,
      seizure, collapse or sudden death was recorded. Risk factors were screened by
      univariable logistic regression prior to multivariable backward stepwise model
      building. RESULTS: In this study, 962 starters (n = 768 dogs) had DF (23.9%), 16
      starters were ataxic (0.4%) and there were no observed cases of collapse, seizure
      or sudden death. Race track location, increasing race distance, race grade based
      on increasing 1st place prize value, lower (earlier) race number at the meeting,
      age, a previous observation of DF at the last start, females, colour (white) and
      better finishing position were all associated with an increased risk of a
      Greyhound being observed with DF. However, when logistic regression assessing the
      random effect of dog was performed, the presence of previous DF was not
      significant. In this cohort, DF was common following strenuous exercise in
      Greyhounds and on its own does not appear to result in reduced performance or
      distress to the animal. CONCLUSION: The incidence of ataxia was low and collapse,
      seizure and sudden death were not observed. However, even though uncommon, ataxia
      has welfare concerns for racing Greyhounds that warrants further investigation.

PMID- 29577257
TI  - Pharmacogenetics of vitamin K antagonists and bleeding risk prediction in atrial
      fibrillation.
AB  - BACKGROUND: Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1)
      and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in
      anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate
      whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for
      major bleeding using the HAS-BLED score. MATERIAL AND METHODS: We recruited 652
      consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at
      least the previous 6 months. A baseline venous blood sample was obtained for DNA
      extraction. We gave an extra point to the HAS-BLED score if the patient was a
      simultaneous carrier of the VKORC1 and CYP2C9 polymorphisms related to bleeding,
      and we called this modified score "GEN|HAS-BLED." During a median follow-up of
      7.6 years (IQR 5.6-8.0), all major bleeding events were recorded. RESULTS: During
      follow-up, 106 (16.2%) patients experienced a major bleeding (2.81%/y; 42
      intracranial haemorrhages and 44 gastrointestinal bleeding) and 24 (3.7%) died
      from major bleeding (0.48%/y). Cox regression analyses demonstrated a significant
      association between HAS-BLED or GEN|HAS-BLED and major bleeds, both as continuous
      or categorical scores. Comparison of receiver operating characteristic (ROC)
      curves shows that original HAS-BLED clinical score had better predictive ability
      than GEN|HAS-BLED (0.660, 95% CI 0.622-0.696 vs 0.645, 95% CI 0.607-0.682; P =
      .030). Discrimination and reclassification analyses showed that GEN|HAS-BLED did
      not improve sensitivity compared with the original score and even showed
      significant negative reclassification. CONCLUSION: Adding pharmacogenetic factors
      (ie polymorphisms of the VKORC1 and CYP2C9 genes) to the HAS-BLED score does not
      improve the prediction or discrimination performance for major bleeding.

PMID- 29577259
TI  - Elevated high-sensitive troponin T in negative stress test individuals.
AB  - BACKGROUND: The exercise ECG stress test (EST) is still the first step of work-up
      in intermediate risk patients in many clinical scenarios. High-sensitive cardiac
      troponin T (hs-cTnT) elevation is related to future cardiovascular events in the
      general population and in patients with ischaemic heart disease. The relation
      between these 2 tests is not well described. MATERIALS AND METHODS: A total of
      2780 participants from the Tel-Aviv Medical Center Inflammation Survey cohort
      (mean age 49 years, 79% men) were analysed. Multiple physiologic and metabolic
      parameters including hs-cTnT were collected. All participants completed an EST
      manually reviewed by a cardiologist. RESULTS: A positive EST was documented in
      224 subjects (8%). The majority (91%) of participants with hs-cTnT levels of 5-14
      ng/L had a negative EST as well as 89.3% of subjects with levels >14 ng/L. The
      proportion of subjects with a positive EST and detectable hs-cTnT levels (>5
      ng/L) was not significantly greater compared to those with a negative EST (53.1%
      vs 46.2%, respectively, P = .09). CONCLUSION: Among subjects referred for EST as
      part of an annual health survey, we found no significant association between EST
      results to hs-cTnT detection.

PMID- 29577258
TI  - Gamma-aminobutyric acid levels in cerebrospinal fluid in neuropaediatric
      disorders.
AB  - AIM: Gamma-aminobutyric acid (GABA) is a major modulator in brain maturation and
      its role in many different neurodevelopmental disorders has been widely reported.
      Although the involvement of GABA in different disorders has been related to its
      regulatory function as an inhibitory neurotransmitter in the mature brain, co
      transmitter, and signalling molecule, little is known about its role as a
      clinical biomarker in neuropaediatric disorders. The aim of this study is to
      report the cerebrospinal fluid (CSF) free-GABA concentrations in a large cohort
      of patients (n=85) with different neurological disorders. METHOD: GABA was
      measured in the CSF of neuropaediatric patients using capillary electrophoresis
      with laser-induced fluorescence detection. Other neurotransmitters (amino acids
      and monoamines) were also analysed. RESULTS: GABA concentrations in CSF were
      abnormal, with a greater frequency (44%) than monoamines (20%) in neuropaediatric
      patients compared with our reference values. Although we included a few patients
      with inborn errors of metabolism, GABA levels in CSF were more frequently
      abnormal in metabolic disorders than in other nosological groups. INTERPRETATION:
      Our work suggests further research into brain GABAergic status in neuropaediatric
      disorders, which could also lead to new therapeutic strategies. WHAT THIS PAPER
      ADDS: Homeostasis of GABA seems more vulnerable than that of monoamines in the
      developing brain. The highest GABA levels are found in the primary GABA
      neurotransmitter disorder SSADH deficiency. GABA alterations are not specific for
      any clinical or neuroimaging presentation.

PMID- 29577260
TI  - Usefulness of The C-Reactive Protein/Albumin Ratio for Predicting No-Reflow in ST
      elevation myocardial infarction treated with primary percutaneous coronary
      intervention.
AB  - BACKGROUND: The ratio of serum C-reactive protein (CRP) to albumin has been
      proven to be a more accurate indicator than albumin and CRP levels alone in
      determining the prognosis of patients with cancer and critical illness. The aim
      of this study was to determine whether the CRP/albumin ratio (CAR) can be linked
      to imperfect reperfusion that can worsen the prognosis of ST-elevation myocardial
      infarction (STEMI) in patients treated with primary percutaneous coronary
      intervention (pPCI). MATERIALS AND METHODS: A total of 1217 consecutive STEMI
      patients who achieved epicardial vessel patency with pPCI were recruited to this
      study. RESULTS: The study population was divided into 2 groups: reflow (n = 874)
      and no-reflow (NR) (n = 343) groups. The white blood cell count (WBC), neutrophil
      to-lymphocyte ratio (NLR) and CAR (0.03 [0.01-0.04] vs 0.06 [0.03-0.12] (P <
      .001) were significantly higher in the NR group than in the reflow group, and
      these factors were found to be independent predictors of NR development. The best
      cut-off value of CAR predicting NR was 0.59 with a sensitivity of 54.7% and
      specificity of 86.7. The predictive power of CAR surpassed that of CRP, albumin,
      WBC count and NLR in the receiver operator curve (ROC) curve comparison.
      CONCLUSION: No-reflow can be predicted by systemic inflammation markers including
      WBC count, NLR and CAR measured from the blood sample obtained on admission. CAR
      has a higher clinical value than CRP, albumin level, WBC count and NLR in NR
      prediction.

PMID- 29577262
TI  - Galli-Galli disease responsive to isotretinoin treatment.

PMID- 29577261
TI  - Clock genes alterations and endocrine disorders.
AB  - BACKGROUND: Various endocrine signals oscillate over the 24-hour period and so
      does the responsiveness of target tissues. These daily oscillations do not occur
      solely in response to external stimuli but are also under the control of an
      intrinsic circadian clock. DESIGN: We searched the PubMed database to identify
      studies describing the associations of clock genes with endocrine diseases.
      RESULTS: Various human single nucleotide polymorphisms of brain and muscle ARNT
      like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes
      exhibited significant associations with type 2 diabetes mellitus. ARNTL2 gene
      expression and upregulation of BMAL1 and PER1 were associated with the
      development of type 1 diabetes mellitus. Thyroid hormones modulated PER2
      expression in a tissue-specific way, whereas BMAL1 regulated the expression of
      type 2 iodothyronine deiodinase in specific tissues. Adrenal gland and adrenal
      adenoma expressed PER1, PER2, CRY2, CLOCK and BMAL1 genes. Adrenal sensitivity to
      adrenocorticotrophin was also affected by circadian oscillations. A significant
      correlation between the expression of propio-melanocorticotrophin and PER 2, as
      well as between prolactin and CLOCK, was found in corticotroph and
      lactosomatotroph cells, respectively, in the pituitary. Clock genes and
      especially BMAL1 showed an important role in fertility, whereas oestradiol and
      androgens exhibited tissue-specific effects on clock gene expression. Metabolic
      disorders were also associated with circadian dysregulation according to studies
      in shift workers. CONCLUSIONS: Clock genes are associated with various endocrine
      disorders through complex mechanisms. However, data on humans are scarce.
      Moreover, clock genes exhibit a tissue-specific expression representing an
      additional level of regulation. Their specific role in endocrine disorders and
      their potential implications remain to be further clarified.

PMID- 29577263
TI  - Multiple keratoacanthoma and oral lichen planus successfully treated with
      systemic retinoids and review of multiple keratoacanthoma associated with lichen
      planus.

PMID- 29577264
TI  - In Our Lives and Under Our Skin: An Investigation of Specific Psychobiological
      Mediators Linking Family Relationships and Health Using the Biobehavioral Family
      Model.
AB  - The objective of this study was to use the Biobehavioral Family Model (BBFM) to
      delineate which psychophysiological variables link romantic and family
      relationship satisfaction variables to health outcomes. Data from individuals who
      reported being partnered from the second wave of the National Survey of Midlife
      Development in the United States (MIDUS II), Project 4 (n = 812) were used to
      test a structural equation model which explored which psychophysiological
      variables potentially mediated associations between positive and negative family
      emotional climate variables and disease activity. This model found that current
      and past family variables had larger associations with the psychophysiological
      variables than romantic partner variables; depressive symptoms, anxiety, and
      inflammation partially mediated associations between family relationships and
      health; and, contrary to the hypotheses, romantic partner and family support were
      linked to worse health outcomes. However, the findings should be viewed with
      regard to the cross-sectional design of the study. Overall, the findings support
      the use of the BBFM as a model that can guide clinical interventions.

PMID- 29577265
TI  - Specificity of the Association between Marital Discord and Longitudinal Changes
      in Symptoms of Depression and Generalized Anxiety Disorder in the Irish
      Longitudinal Study on Ageing.
AB  - This longitudinal study was conducted to evaluate actor and partner effects of
      marital discord on changes in symptoms of depression and generalized anxiety
      disorder (GAD) in a large population sample of Irish adults (N = 1,445 couples),
      adjusting for the potential confounds of quality of other social relationships
      and other psychopathology symptoms. The Actor-Partner Interdependence Model was
      used to examine actor and partner effects of marital discord on changes in
      symptoms of depression and GAD at a 2-year follow-up. Additional models examined
      these associations adjusting for family and friend discord and symptoms of the
      other type of psychopathology (depressive or GAD symptoms). Actor effects of
      marital discord on depressive and anxiety symptoms were greater for men than for
      women. There were significant, positive actor effects of marital discord on
      depressive symptoms for husbands and wives, which remained significant when
      adjusting for family and friend discord and GAD symptoms. There were significant,
      positive actor effects of marital discord on GAD symptoms for husbands, which
      remained significant when adjusting for family and friend discord and depressive
      symptoms. Results demonstrate that longitudinal associations between marital
      discord and depressive symptoms (for wives and husbands) and GAD symptoms (for
      husbands) are incremental to other rival explanations (family and friend discord
      and the other set of symptoms). Findings provide evidence for a potential causal
      association leading from marital discord to symptoms of depression and GAD.

PMID- 29577266
TI  - Knowledge, attitudes and practices regarding methicillin-resistant Staphylococcus
      aureus (MRSA) infection control and nasal MRSA carriage rate among dental health
      care professionals.
AB  - BACKGROUND: Dental health-care professionals (DHCPs) with nasal colonisation of
      methicillin-resistant Staphylococcus aureus (MRSA) can serve as a reservoir for
      MRSA transmission to others and be exposed to self-contamination with MRSA.
      Evaluating the knowledge, attitudes and actual practice of DHCPs is imperative
      for appropriate infection control. METHODS: Dentists, dental hygienists and
      dental technologists from Seoul National University Dental Hospital were
      recruited to participate in a cross-sectional survey and undergo nasal sampling
      of MRSA. The survey included demographic questions, six questions about
      knowledge, eight questions about attitudes/perceptions and six questions about
      practices/behaviours regarding MRSA infection control. Nasal samples from the
      participants were analysed for MRSA presence, antimicrobial susceptibility and
      staphylococcal cassette chromosome mec (SCCmec) typing. MRSA carriers underwent
      decolonisation with topical mupirocin. RESULTS: Among 139 DHCPs, four (2.9%) were
      nasal MRSA carriers. Decolonisation was successful in three participants. One
      participant was decolonised with topical fusidic acid after failure to decolonise
      with mupirocin. Dentists had a higher knowledge score compared with the other
      professionals (P < 0.05). Dental hygienists scored higher on practice questions
      compared with the other professionals (P < 0.05). There was a significant,
      positive correlation between attitude and practice scores (P < 0.01).
      CONCLUSIONS: The nasal MRSA carriage rate among DHCPs is 2.9%, which is higher
      than that in the general population but lower than that in other health-care
      professionals. Further education of DHCPs on MRSA, especially regarding its
      seriousness, is needed to improve MRSA infection control in a dental hospital
      setting.

PMID- 29577267
TI  - Parental Perceptions of Individual and Dyadic Adjustment as Predictors of
      Observed Coparenting Cohesion: A Cross-National Study.
AB  - : Over the past 20 years, systemically guided approaches to understanding early
      family processes have helped to provide greater clarity concerning the interplay
      among individual, dyadic, and family level processes. Parental depression,
      marital functioning, and child adjustment in particular appear to be reliable
      predictors of coparental and family level functioning. Indeed, cohesion at the
      level of the family group covaries in theoretically meaningful ways with these
      indicators of individual and dyadic adjustment. In this study, two collaborating
      research groups (one in Switzerland, the second in the United States) partnered
      to examine whether similar patterns of relationships exist among individual and
      marital adjustment and coparenting processes in families of 4-year-old children.
      Using similar constructs but disparate and occasionally dissimilar measures, both
      groups measured parent-reported depression, marital satisfaction, and child
      behavior problems. Coparenting cooperation and warmth were observed during family
      interactions. Despite differences between samples and evaluation tools, similar
      results were found for the Swiss and U.S. SAMPLES: A model with depression,
      marital satisfaction, and child symptoms as predictors of a latent factor of
      observed coparenting cooperation and warmth showed good fit to data in both
      samples, suggesting the model was relevant for each. Parameter estimation showed
      that higher coparenting cooperation and warmth was predicted by lower maternal
      depression and higher child internalizing symptoms. The common significant
      effects despite differences in assessment paradigms and instrumentation are of
      substantive interest. Future directions pertinent to the coparenting questions
      addressed in this research are discussed.

PMID- 29577268
TI  - Associations of Army Fathers' PTSD Symptoms and Child Functioning: Within- and
      Between-Family Effects.
AB  - This study examined the within-family and between-family associations between
      fathers' military-related PTSD symptoms and parent ratings of children's
      behavioral and emotional problems. The sample included married couples (N = 419)
      with children composed of a civilian wife and an active-duty husband serving in
      the U.S. Army. Results indicate that changes in fathers' PTSD symptoms over time
      were associated with corresponding changes in both mothers' and fathers' reports
      of child behavioral and emotional problems. These within-family findings were
      independent from between-family effects, which showed that higher average PTSD
      symptomatology was associated with more overall behavioral and emotional problems
      for children. This study uses advances in statistical methodologies to increase
      knowledge about how PTSD symptoms and child problems are related, both across
      different families and over time within families.

PMID- 29577269
TI  - PME-1 is regulated by USP36 in ERK and Akt signaling pathways.
AB  - Deubiquitinating enzymes (DUBs) play an important role in the ubiquitin
      proteasome system (UPS) by eliminating ubiquitins from substrates and inhibiting
      proteasomal degradation. Protein phosphatase methylesterase 1 (PME-1) inactivates
      protein phosphatase 2A (PP2A) and enhances the ERK and Akt signaling pathways,
      which increase cell proliferation and malignant cell transformation. In this
      study, we demonstrate that USP36 regulates PME-1 through its deubiquitinating
      enzyme activity. USP36 increases PME-1 stability, and depletion of USP36
      decreases the PME-1 expression level. Furthermore, we demonstrate that USP36
      promotes the ERK and Akt signaling pathways. In summary, it is suggested that
      USP36 regulates PME-1 as a DUB and participates in the ERK and Akt signaling
      pathways.

PMID- 29577270
TI  - Cardiovascular Reactivity During Marital Conflict in Laboratory and Naturalistic
      Settings: Differential Associations with Relationship and Individual Functioning
      Across Contexts.
AB  - Cardiovascular reactivity during spousal conflict is considered to be one of the
      main pathways for relationship distress to impact physical, mental, and
      relationship health. However, the magnitude of association between cardiovascular
      reactivity during laboratory marital conflict and relationship functioning is
      small and inconsistent given the scope of its importance in theoretical models of
      intimate relationships. This study tests the possibility that cardiovascular data
      collected in laboratory settings downwardly bias the magnitude of these
      associations when compared to measures obtained in naturalistic settings.
      Ambulatory cardiovascular reactivity data were collected from 20 couples during
      two relationship conflicts in a research laboratory, two planned relationship
      conflicts at couples' homes, and two spontaneous relationship conflicts during
      couples' daily lives. Associations between self-report measures of relationship
      functioning, individual functioning, and cardiovascular reactivity across
      settings are tested using multilevel models. Cardiovascular reactivity was
      significantly larger during planned and spontaneous relationship conflicts in
      naturalistic settings than during planned relationship conflicts in the
      laboratory. Similarly, associations with relationship and individual functioning
      variables were statistically significantly larger for cardiovascular data
      collected in naturalistic settings than the same data collected in the
      laboratory. Our findings suggest that cardiovascular reactivity during spousal
      conflict in naturalistic settings is statistically significantly different from
      that elicited in laboratory settings both in magnitude and in the pattern of
      associations with a wide range of inter- and intrapersonal variables. These
      differences in findings across laboratory and naturalistic physiological
      responses highlight the value of testing physiological phenomena across
      interaction contexts in romantic relationships.

PMID- 29577271
TI  - Anatomic relationship of internal cervical os to maternal bladder in pregnancies
      at low and high risk of preterm delivery.

PMID- 29577272
TI  - Effect of a tissue selective estrogen complex on breast cancer: Role of unique
      properties of conjugated equine estrogen.
AB  - The Women's Health Initiative studies reported that the menopausal hormone
      therapy (MHT) regimen containing conjugated equine estrogen (CEE) and
      medroxyprogesterone acetate increased, whereas CEE alone reduced breast cancer
      incidence. These observations suggest the possibility that CEE might exert unique
      actions on breast and also suggest the need to eliminate the progestogen from MHT
      regimens. A MHT regimen called a tissue selective estrogen complex (TSEC),
      containing CEE plus bazedoxifene (BZA), to avoid the need for a progestogen, was
      developed and FDA approved. Our study addressed two questions regarding this
      TSEC: (i) whether CEE exert effects on breast cancer which differ from those of
      estradiol (E2 ) and (ii) whether BZA antagonize the effects of E2 and CEE on
      breast cancer? Two rodent models (NMU and ACI) were used to compare the effect of
      CEE with E2 on mammary tumor formation, proliferation and apoptosis. In both the
      NMU and ACI models, E2 significantly increased tumor incidence and multiplicity
      whereas in striking contrast CEE did not, even though the estrogenic effects of
      CEE and E2 on uterine weight were identical. Mechanistically E2 blocked whereas
      CEE stimulated apoptosis (cleaved caspase-3) in ACI animals and only E2
      stimulated proliferation (Ki67). BZA exerted highly potent anti-estrogenic
      effects on tumors by completely blocking palpable tumor formation. These data
      suggest that the CEE/BZA TSEC may be a safer, breast-antagonistic, MHT agent for
      women and might have potential to prevent breast cancer while relieving
      menopausal symptoms.

PMID- 29577273
TI  - Impact of introducing specific measures to reduce the frequency of cesarean
      delivery for non-obstetric indications.
AB  - OBJECTIVE: To identify the frequency of cesarean delivery for non-obstetric
      indications before and after the introduction of specific measures to lower the
      rate of elective cesarean, and to evaluate the effectiveness of the introduced
      measures. METHODS: In the present single-center retrospective cohort study at
      University Hospital Trnava, Trnava, Slovak Republic, the frequency of elective
      cesarean was evaluated before (January 1, 2010, to December 31, 2014) and after
      (January 1, 2015, to December 31, 2016) the implementation of specific measures
      applied in January 2015 to confirm the indications for primary cesarean delivery.
      The frequency of elective cesarean delivery for non-obstetric indications was
      compared between the two periods. RESULTS: Before the intervention in 2015, 229
      (2.9%) of 7768 women had elective cesarean deliveries for non-obstetric
      indications. After implementation of the intervention, the frequency decreased to
      27 (0.8%) of 3203 women (P<0.001). CONCLUSION: The frequency of cesarean delivery
      for non-obstetric indications was reduced significantly by introducing specific
      reasonable measures. These included all non-obstetric indications for cesarean
      delivery being approved by a leading specialist of the related department, close
      cooperation with professionals from other specialties, and, additionally, staff
      attending professional educational lectures.

PMID- 29577274
TI  - Disentangling the effects of multiple environmental drivers on population changes
      within communities.
AB  - The effects of different environmental drivers on the changes in species'
      population abundances can be difficult to disentangle as they often act
      simultaneously. Researchers have built statistical models that include
      environmental variables (such as annual temperature) or species attributes (such
      as a species' temperature preference), which are assumed to detect the impacts of
      specific drivers (such as climate change). However, these approaches are often
      applied separately or, if combined, not explicitly compared. We show the
      complementary insights gained by applying both these approaches to a community
      dataset on Danish terrestrial birds. We use our analysis to compare the relative
      importance of climate change and agricultural land-use change for the abundance
      changes within the community between 1983 and 2013. Population models were fitted
      to the community data of species' annual abundances with predictors comprising:
      species attributes (species' temperature and habitat preferences), environmental
      variables (climatic and agricultural land-use change variables) or both.
      Relationships between species' abundances and environmental variables were used
      to identify the drivers associated with average abundance changes of species in
      the community. Relationships between species' abundances and their attributes
      were used to understand the drivers causing interspecific variation in abundance
      changes. Warmer winters were positively associated with community-level
      abundances, and warm-adapted species had more positive abundance changes than
      cold-adapted ones. Agricultural land-use area was negatively associated with
      community-level abundances, and birds using a high proportion of meadow and
      habitat specialists had more negative abundance changes than birds using other
      habitats and habitat generalists. Effect sizes of environmental variables were
      larger for agricultural land-use change while those of species attributes were
      larger for climate change. The environmental data approach suggested that
      agricultural land-use change has decreased the average abundances of species in
      the community, affecting total community size while the species attribute-based
      approach suggested that climate change has caused variation in abundance among
      species, affecting community composition. Environmental variables and species
      attributes that are hypothesized to link to specific drivers can be used together
      to provide complementary information on the impacts of different drivers on
      communities.

PMID- 29577275
TI  - Central place foragers and moving stimuli: A hidden-state model to discriminate
      the processes affecting movement.
AB  - Human activities can influence the movement of organisms, either repelling or
      attracting individuals depending on whether they interfere with natural
      behavioural patterns or enhance access to food. To discern the processes
      affecting such interactions, an appropriate analytical approach must reflect the
      motivations driving behavioural decisions at multiple scales. In this study, we
      developed a modelling framework for the analysis of foraging trips by central
      place foragers. By recognising the distinction between movement phases at a
      larger scale and movement steps at a finer scale, our model can identify periods
      when animals are actively following moving attractors in their landscape. We
      applied the framework to GPS tracking data of northern fulmars Fulmarus
      glacialis, paired with contemporaneous fishing boat locations, to quantify the
      putative scavenging activity of these seabirds on discarded fish and offal. We
      estimated the rate and scale of interaction between individual birds and fishing
      boats and the interplay with other aspects of a foraging trip. The model
      classified periods when birds were heading out to sea, returning towards the
      colony or following the closest boat. The probability of switching towards a boat
      declined with distance and varied depending on the phase of the trip. The maximum
      distance at which a bird switched towards the closest boat was estimated around
      35 km, suggesting the use of olfactory information to locate food. Individuals
      spent a quarter of a foraging trip, on average, following fishing boats, with
      marked heterogeneity among trips and individuals. Our approach can be used to
      characterise interactions between central place foragers and different
      anthropogenic or natural stimuli. The model identifies the processes influencing
      central place foraging at multiple scales, which can improve our understanding of
      the mechanisms underlying movement behaviour and characterise individual
      variation in interactions with a range of human activities that may attract or
      repel these species. Therefore, it can be adapted to explore the movement of
      other species that are subject to multiple dynamic drivers.

PMID- 29577276
TI  - Soluble gammac receptor attenuates anti-tumor responses of CD8+ T cells in T cell
      immunotherapy.
AB  - Previous studies have shown that soluble common gamma-chain (sgammac) modulates
      CD4+ T cell immunity with antagonistic functions in gammac cytokine signaling.
      However, the role of sgammac in functional properties of effector CD8+ T cells
      has not been fully defined. In this study, we report a new mechanism by which the
      anti-tumor activity of mouse CD8+ T cells is suppressed in sgammac of their own
      producing. While sgammac significantly inhibits cytotoxicity of CD8+ T cells,
      blocking sgammac production by genetic modification leads to potentiated effector
      function of CD8+ T cells, establishing persistent CD8+ T cells. This is due to
      the modulation of IL-2 and IL-15 signaling, which is required for expansion and
      survival of CD8+ T cells as well as for optimal cytotoxic activity. More
      efficient management of tumor growth was achieved by an adoptive transfer of
      sgammac-deficient CD8+ T cells than that of wild-type or sgammac-overexpressing
      CD8+ T cells. Blocking of IL-2 and IL-15 signaling by sgammac attenuates the
      capacity of CD8+ T cells to mount an optimal response to the tumor, with both
      quantitative and qualitative effects on antigen-specific CD8+ T cells. These
      results could have a critical implication for the generation and survival of
      optimal effector T cells for adoptive immunotherapy of cancer.

PMID- 29577277
TI  - Alternative splice variants of DCLK1 mark cancer stem cells, promote self-renewal
      and drug-resistance, and can be targeted to inhibit tumorigenesis in kidney
      cancer.
AB  - Renal cell carcinoma (RCC) is a common and devastating disease characterized by a
      hypoxic microenvironment, epithelial-mesenchymal transition and potent resistance
      to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC
      markers have been studied in RCC, but overall there is limited data on their role
      and most markers studied have been relatively nonspecific. Doublecortin-like
      kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and
      evidence for an equivalent role in other cancers is accumulating. We used
      bioinformatics, immunohistochemistry, flow cytometry, spheroid self-renewal and
      chemoresistance assays in combination with overexpression and siRNA-knockdown to
      study the stem cell-supportive role of DCLK1 alternative splice variants (DCLK1
      ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed
      a novel monoclonal antibody (CBT-15) and delivered it systemically to RCC tumor
      xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and
      predictive of overall and recurrence-free survival in RCC patients. In vitro,
      DCLK1 ASVs were able to directly stimulate essential molecular and functional
      characteristics of renal CSCs including expression of aldehyde dehydrogenase,
      self-renewal and resistance to FDA-approved receptor tyrosine kinase and mTOR
      inhibitors, while targeted downregulation of DCLK1 reversed these
      characteristics. Finally, targeting DCLK1 ASV-positive cells with the novel CBT
      15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings
      establish DCLK1 as a CSC marker with implications for therapy, disease
      progression and survival in RCC and demonstrate the therapeutic value of DCLK1
      targeted monoclonal antibodies against renal CSCs.

PMID- 29577278
TI  - Evaluation of Enterococcus faecium NRRL B-2354 as a Surrogate for Salmonella
      During Extrusion of Low-Moisture Food.
AB  - : Salmonella in low-moisture foods is an emerging challenge due to numerous food
      product recalls and foodborne illness outbreaks. Identification of suitable
      surrogate is critical for process validation at industry level due to
      implementation of new Food Safety Modernization Act of 2011. The objective of
      this study was to evaluate Enterococcus faecium NRRL B-2354 as a surrogate for
      Salmonella during the extrusion of low-moisture food. Oat flour, a low-moisture
      food, was adjusted to different moisture (14% to 26% wet basis) and fat (5% to
      15% w/w) contents and was inoculated with E. faecium NRRL B-2354. Inoculated
      material was then extruded in a lab-scale single-screw extruder running at
      different screw speeds (75 to 225 rpm) and different temperatures (75, 85, and 95
      degrees C). A split-plot central composite 2nd order response surface design was
      used, with the central point replicated six times. The data from the selective
      media (m-Enterococcus agar) was used to build the response surface model for
      inactivation of E. faecium NRRL B-2354. Results indicated that E. faecium NRRL B
      2354 always had higher heat resistance compared to Salmonella at all conditions
      evaluated in this study. However, the patterns of contour plots showing the
      effect of various product and process parameters on inactivation of E. faecium
      NRRL B-2354 was different from that of Salmonella. Although E. faecium NRRL B
      2354 may be an acceptable surrogate for extrusion of low-moisture products due to
      higher resistance than Salmonella, another surrogate with similar inactivation
      behavior may be preferred and needs to be identified. PRACTICAL APPLICATION: Food
      Safety Modernization Act requires the food industry to validate processing
      interventions. This study validated extrusion processing and demonstrated that E.
      faecium NRRL B-2354 is an acceptable surrogate for extrusion of low-moisture
      products. The developed response surface model allows the industry to identify
      process conditions to achieve a desired lethality for their products based on
      composition.

PMID- 29577279
TI  - Partitioning of the primate intraparietal cortex based on connectivity pattern
      and immunohistochemistry for Cat-301 and SMI-32.
AB  - We propose a partitioning of the primate intraparietal sulcus (IPS) using
      immunoarchitectural and connectivity criteria. We studied the immunoarchitecture
      of the IPS areas in the capuchin monkey using Cat-301 and SMI-32
      immunohistochemistry. In addition, we investigated the IPS projections to areas
      V4, TEO, PO, and MT using retrograde tracer injections in nine hemispheres of
      seven animals. The pattern and distribution of Cat-301 and SMI-32 immunostaining
      revealed multiple areas in the IPS, in the adjoining PO cleft and in the
      annectant gyrus, with differential staining patterns found for areas V3d, DM,
      V3A, DI, PO, POd, CIP-1, CIP-2, VIPa, VIPp, LIPva, LIPvp, LIPda, LIPdp, PIPv,
      PIPd, MIPv, MIPd, AIPda, AIPdp, and AIPv. Areas V4, TEO, PO, MT, which belong to
      different cortical streams of visual information processing, receive projections
      from at least twenty different areas within the IPS and adjoining regions. In six
      animals, we analyzed the distribution of retrogradely labeled cells in tangential
      sections of flat-mount IPS preparations. The lateral bank of the IPS projects to
      regions belonging both to the ventral (V4 and TEO) and dorsal (PO and MT)
      streams. The region on the floor of the IPS (i.e., VIP) projects predominantly to
      dorsal stream areas. Finally, the medial bank of the IPS (i.e., MIP) projects
      solely to the dorsalmedial stream (PO). Therefore, our data suggest that ventral
      and dorsal streams remain segregated within the IPS, and that its projections to
      the dorsal stream can be further segregated based on those targeting the
      dorsolateral versus the dorsomedial subdivisions.

PMID- 29577281
TI  - Effects of therapist-worn protective equipment during functional analysis of
      aggression.
AB  - The effects of therapist-worn protective equipment (PE) on functional analysis
      (FA) outcomes for aggression were evaluated. Independent FAs with and without PE
      were conducted concurrently. Both FAs showed the same function of aggression for
      all participants. These results suggest that therapists may wear PE during FAs of
      aggression to reduce risk without altering the interpretation of the analysis.

PMID- 29577280
TI  - Emerging depression in adolescence coincides with accelerated frontal cortical
      thinning.
AB  - BACKGROUND: Adolescence is a transition period characterized by heightened
      emotional reactivity, which for some sets the stage for emerging depressive
      symptoms. Prior studies suggest that adolescent depression is associated with
      deviant cortical and subcortical brain structure. Longitudinal studies are,
      however, currently scarce, but critical to detect which adolescents are at risk
      for developing depressive symptoms. METHODS: In this longitudinal study, a
      community sample of 205 participants underwent magnetic resonance imaging (MRI)
      in three biennial waves (522 scans) spanning 5 years across ages 8-25 years.
      Depressive symptomatology was assessed using self-report at the third time point.
      Mixed models were used to examine the relations between structural brain
      development, specifically regional change in cortical thickness, surface area and
      subcortical volumes (hippocampus and amygdala), and depressive symptoms. RESULTS:
      Accelerated frontal lobe cortical thinning was observed in adolescents who
      developed depressive symptoms at the third time point. This effect remained after
      controlling for parent-reported affective problems at the first time point.
      Moreover, the effect was driven by specific lateral orbitofrontal and precentral
      regions. In addition, differential developmental trajectories of parietal
      cortical thickness and surface area in several regions were found for
      participants reporting higher depressive symptomatology, but these results did
      not survive correction for multiple comparisons. Volumes or developmental volume
      changes in hippocampus or amygdala were not related to depressive symptoms.
      CONCLUSIONS: This study showed that emerging depression is associated with
      cortical thinning in frontal regions within individuals. These findings move
      beyond detecting cross-sectional correlations and set the stage for early
      detection, which may inform future intervention.

PMID- 29577282
TI  - Tag retention and mortality of adult Atlantic salmon Salmo salar gastrically
      tagged with different sized telemetry transmitters.
AB  - A batch of 1 sea winter pre-spawning adult Salmo salar from the Bush river in
      Northern Ireland, U.K., were gastrically tagged with large (13 mm diameter) and
      small (9 mm diameter) dummy acoustic telemetry tags alongside untagged control
      fish. Survival differed between control and tagged fish and the estimated
      probability of survival by the end of the study for control fish with no tag was
      0.94, small tags was 0.90 and large tags was 0.72. Tag loss through regurgitation
      was slightly higher for fish tagged with larger tags than for fish tagged with
      smaller tags and the estimated probability of tag loss for fish with a small tag
      was 0.10 and for large tags was 0.14.

PMID- 29577283
TI  - Morphological characterization of HVC projection neurons in the zebra finch
      (Taeniopygia guttata).
AB  - Singing behavior in the adult male zebra finch is dependent upon the activity of
      a cortical region known as HVC (proper name). The vast majority of HVC projection
      neurons send primary axons to either the downstream premotor nucleus RA (robust
      nucleus of the arcopallium, or primary motor cortex) or Area X (basal ganglia),
      which play important roles in song production or song learning, respectively. In
      addition to these long-range outputs, HVC neurons also send local axon
      collaterals throughout that nucleus. Despite their implications for a range of
      circuit models, these local processes have never been completely reconstructed.
      Here, we use in vivo single-neuron Neurobiotin fills to examine 40 projection
      neurons across 31 birds with somatic positions distributed across HVC. We show
      that HVC(RA) and HVC(X) neurons have categorically distinct dendritic fields.
      Additionally, these cell classes send axon collaterals that are either restricted
      to a small portion of HVC ("local neurons") or broadly distributed throughout the
      entire nucleus ("broadcast neurons"). Overall, these processes within HVC offer a
      structural basis for significant local processing underlying behaviorally
      relevant population activity.

PMID- 29577284
TI  - Regulation of eye and jaw colouration in three-spined stickleback Gasterosteus
      aculeatus.
AB  - Fish can change their skin and eye colour for background matching and signalling.
      Males of Gasterosteus aculeatus develop ornamental blue eyes and a red jaw during
      the reproductive season, colours that are further enhanced during courtship.
      Here, the effects of different hormones on physiological colour changes in the
      eyes and jaws of male and female G. aculeatus were investigated in vitro. In an
      in vivo experiment, G. aculeatus were injected with a receptor blocker of a
      pivotal hormone (noradrenaline) that controls colour change. In males,
      noradrenaline had aggregating effects on melanophore and erythrophore pigments
      resulting in blue eyes and a pale jaw, whereas melanocyte-concentrating hormone
      (MCH) and melatonin resulted in a pale jaw only. When noradrenalin was combined
      with melanocyte stimulating hormone (MSH) or prolactin, the jaw became red, while
      the eyes remained blue. In vivo injection of yohimbine, an alpha-2 adrenoreceptor
      blocker, resulted in dispersion of melanophore pigment in the eyes and inhibited
      the blue colouration. Altogether, the data suggest that noradrenalin has a
      pivotal role in the short-term enhancement of the ornamental colouration of male
      G. aculeatus, potentially together with MSH or prolactin. This study also found a
      sex difference in the response to MCH, prolactin and melatonin, which may result
      from different appearance strategies in males, versus the more cryptic females.

PMID- 29577285
TI  - Application of Lactobacillus plantarum in Functional Products Based on Fermented
      Buckwheat.
AB  - In this work, 12 plant-based potential probiotic mashes were produced by
      fermenting buckwheat with lactic acid cocci of the Fresco DVS 1010 culture and
      the human-derived isolate Lactobacillus plantarum HM1. The effect of single and
      coculture fermentation was studied at 30 and 37 +/- 0.5  degrees C for 8 hr (5%
      CO2 ), followed by a storage period of 21 days (6 +/- 0.5  degrees C). Although
      milk is the typical growth medium for lactic acid bacteria (LAB), presumably
      viable counts of Fresco reached levels of 108 to 109 CFU/mL (specific growth
      rates ranging from 1.07 to 1.40 hr-1 ) with higher counts in coculture
      fermentation (13%) that differed statistically significantly (P < 0.05). After
      storage, 194 to 4700 mg/kg lactic acid was found in the mashes, with
      significantly higher contents after cocultivation (11% to 96%). Based on the
      overall acceptance of the designed products, milk-based mashes right after the
      fermentation were evaluated as the most satisfactory (3.3 to 3.6). Those after
      the storage period (21 days) exhibited an attractive sensory acceptability (2.2
      to 3.2).

PMID- 29577286
TI  - Antimicrobial Carvacrol in Solution Blow-Spun Fish-Skin Gelatin Nanofibers.
AB  - : Carvacrol is a volatile monoterpenic phenol and main component of oregano
      essential oil that shows nonspecific antimicrobial activity against foodborne
      pathogenic bacteria. Fish-skin gelatin (FSG) nanofibers encapsulating carvacrol
      (15%, 20%, 25%, and 30%, w/w FSG) were successfully prepared via solution blow
      spinning (SBS) technique using lecithin (2.475% wb) as the surfactant. FSG
      emulsions with lower carvacrol ratios (5% and 10%) showed higher values in
      particle size and surface tension as well as lower values in viscosity and
      modulus, which led to failure of maintaining nanofibers shape. The formed
      carvacrol-FSG nanofibers showed round and smooth morphologies with average fiber
      diameters ranging from 103.2 to 138.1 nm as the carvacrol ratio increased from
      15% to 30%. Carvacrol was evenly dispersed within the interior of nanofiber
      matrix. All carvacrol-FSG nanofibers showed inhibitive effects against the growth
      of Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Moreover,
      nanofibers with lower carvacrol ratios showed bigger inhibition zones for E. coli
      and L. monocytogenes (20 mm compared with 12.5 mm for lowest to highest carvacrol
      ratios, respectively). Nanofibers stored at 20  degrees C (51% RH) showed better
      retention (40% to 60%) for carvacrol during the first 4 weeks of storage, while
      nanofibers stored at 2  degrees C (70% RH) showed better retention (10% to 30%)
      at the end of storage. PRACTICAL APPLICATION: Results obtained in the study may
      help with antimicrobial carvacrol addition levels for gelatin fiber preparation
      using solution blow spinning (SBS) method. SBS gelatin fibers with added
      antimicrobials have potential applications for food packaging and medical wound
      dressing.

PMID- 29577287
TI  - Evaluation of Models for Temperature-Dependent Viscosity Changes in Dairy Protein
      Beverage Formulations During Thermal Processing.
AB  - : Rheological modeling as a function of temperature is a useful tool for
      describing products undergoing thermal processing. The rheological behavior of a
      range of dairy-based (4%, w/w) protein beverages was investigated for
      applicability to semi-empirical temperature-dependent viscosity equations. The
      viscosity at 16.8 rad/s of the beverages was measured during heating, holding,
      and cooling over a temperature range of 25 to 90 o C using a rheometer with
      starch pasting cell geometry. Five established fitting methods were applied based
      on the Arrhenius and Williams-Landel-Ferry (WLF) equations using nonlinear
      regression analysis. A two-parameter WLF (WLF2 ) model, using viscosity at a
      reference temperature of 25 o C resulted in high R2 values (0.974 to 0.988) and a
      statistically superior fit compared to the Arrhenius, Generalized Arrhenius, and
      exponential equations (P < 0.001). Deviation from the WLF2 modeled equation was
      used to describe and investigate the effect formulation had on the changes in
      viscosity during thermal heating. This study successfully applied the WLF
      equation to a liquid protein system, proving that a consistent and close fit can
      be achieved across a range of formulations. A rapid, quantitative method for
      viscosity-temperature profile evaluation is presented, which can ease product
      development and optimization of product processing stability. PRACTICAL
      APPLICATION: This study validated the use of the Williams-Landel-Ferry equation
      to describe the behavior of dairy beverages during thermal processing, providing
      a better fit to rheological data than the widely used Arrhenius-based equations.
      In conjunction with the WLF equation, a method was presented which reduced the
      complex rheological data to a single value, which can aid in the comparison of
      formulations for product development and optimization in both research and
      industry.

PMID- 29577288
TI  - Development of Anti-Insect Microencapsulated Polypropylene Films Using a Large
      Scale Film Coating System.
AB  - : Films containing microencapsulated cinnamon oil (CO) were developed using a
      large-scale production system to protect against the Indian meal moth (Plodia
      interpunctella). CO at concentrations of 0%, 0.8%, or 1.7% (w/w ink mixture) was
      microencapsulated with polyvinyl alcohol. The microencapsulated CO emulsion was
      mixed with ink (47% or 59%, w/w) and thinner (20% or 25%, w/w) and coated on
      polypropylene (PP) films. The PP film was then laminated with a low-density
      polyethylene (LDPE) film on the coated side. The film with microencapsulated CO
      at 1.7% repelled P. interpunctella most effectively. Microencapsulation did not
      negatively affect insect repelling activity. The release rate of cinnamaldehyde,
      an active repellent, was lower when CO was microencapsulated than that in the
      absence of microencapsulation. Thermogravimetric analysis exhibited that
      microencapsulation prevented the volatilization of CO. The tensile strength,
      percentage elongation at break, elastic modulus, and water vapor permeability of
      the films indicated that microencapsulation did not affect the tensile and
      moisture barrier properties (P > 0.05). The results of this study suggest that
      effective films for the prevention of Indian meal moth invasion can be produced
      by the microencapsulation of CO using a large-scale film production system.
      PRACTICAL APPLICATION: Low-density polyethylene-laminated polypropylene films
      printed with ink incorporating microencapsulated cinnamon oil using a large-scale
      film production system effectively repelled Indian meal moth larvae. Without
      altering the tensile and moisture barrier properties of the film,
      microencapsulation resulted in the release of an active repellent for extended
      periods with a high thermal stability of cinnamon oil, enabling commercial film
      production at high temperatures. This anti-insect film system may have
      applications to other food-packaging films that use the same ink-printing
      platform.

PMID- 29577289
TI  - Drivers of Preference and Perception of Freshness in Roasted Peanuts (Arachis
      spp.) for European Consumers.
AB  - : Roasted peanuts are a popular snack in Europe, but their drivers of liking and
      perceived freshness have not been previously studied with European consumers.
      Consumer research to date has been focused on U.S. consumers, and only on
      specific peanut cultivars. In this study, 26 unique samples were produced from
      peanuts of different types, cultivars, origins, and with different process
      technologies (including baking, frying, and maceration). The peanut samples were
      subjected to sensory (expert panel, SpectrumTM ) and instrumental analysis
      (color, headspace volatiles, sugar profile, large deformation compression tests,
      and graded by size) and were hedonically rated by consumers in The Netherlands,
      Spain, and Turkey (n > 200 each). Preference Mapping (PREFMAP) on mean liking
      models revealed that the drivers of liking are similar across the three
      countries. Sweet taste, roasted peanut, dark roast, and sweet aromas and the
      color b* value were related to increased liking, and raw bean aroma and bitter
      taste with decreased liking. Further partial least square regression (PLSR)
      modeling of liking and perceived freshness against instrumental attributes showed
      that the color coordinates in combination with sucrose content and a select few
      headspace volatiles were strong predictors of both preference and perceived
      freshness. Finally, additional PLSR models focusing on the headspace volatiles
      only showed that liking and ''fresh'' attributes were correlated with the
      presence of several pyrroles in the volatile fraction, and inversely related to
      ''stale'' and to hexanal and 2-heptanone. PRACTICAL APPLICATION: This study
      provides insight into which flavor, taste, and appearance attributes drive liking
      and disliking of roasted peanuts for European consumers. The drivers are linked
      back to analytical attributes that can be measured instrumentally, thereby
      reducing the reliance on costly sensory panels. Particular emphasis is placed on
      color as a predictor of preference, because of the low cost of the measuring
      equipment, it is available to even smaller producers. In addition to preference,
      the study also examines whether product attributes that drive perceived freshness
      exist. The results can be used to design products with high acceptability across
      several countries within Europe.

PMID- 29577290
TI  - Aluminum and Heavy Metal Accumulation in Tea Leaves: An Interplay of
      Environmental and Plant Factors and an Assessment of Exposure Risks to Consumers.
AB  - : Environmental and plant factors (soil condition, variety, season, and maturity)
      and exposure risks of aluminum (Al), manganese (Mn), lead (Pb), cadmium (Cd), and
      copper (Cu) in tea leaves were investigated. The concentrations of these metals
      in tea leaves could not be predicted by their total concentrations in the soil.
      During any one season, there were differences in Al, Mn, and Cd levels between
      tea varieties. Seasonally, autumn tea and/or summer tea had far higher levels of
      Al, Mn, Pb, and Cd than did spring tea. Tea leaf maturity positively correlated
      with the concentrations of Al, Mn, Pb, and Cd, but negatively with Cu. The
      calculated average daily intake doses (mg/ [kg*d]) for these metal elements were
      0.14 (Al), 0.11 (Mn), 2.70 * 10-3 (Cu), 2.80 * 10-4 (Pb), and 2.88 * 10-6 (Cd).
      The hazard quotient values of each metal were all significantly lower than risk
      level (=1), suggesting that, for the general population, consumption of tea does
      not result in the intake of excessive amounts of Al, Mn, Pb, Cd, or Cu. This
      study identified the factors that can be monitored in the field to decrease
      consumer exposure to Al and Mn through tea consumption. PRACTICAL APPLICATION:
      Environmental and plant factors influence aluminum and heavy metal accumulation
      in tea leaves. Consumers of tea are not ingesting excessive Al, Mn, Pb, Cd, or
      Cu. Trackable factors were identified to manage exposure levels.

PMID- 29577291
TI  - Validation of a QuEChERS-Based Gas Chromatography-Mass Spectrometry (GC-MS)
      Method for Analysis of Phthalate Esters in Grain Sorghum.
AB  - : A modified QuEChERS method coupled with gas chromatography-mass spectrometry
      (GC-MS) was developed for analysis of 14 phthalate esters (PAEs) in grain sorghum
      (GS). Chemical extraction was done with acetonitrile followed by dispersive-solid
      phase extraction technique with a mixture of sorbents including primary secondary
      amine and octadecyl silica. Under the optimized condition, the matrix-matched
      calibration curves for all PAEs showed good linear relationship in the
      concentration range between 5 and 500 MUg/L with correlation coefficients (R2 )
      better than 0.99. Mean recoveries were between 82.0% and 120.2% at spiking levels
      of 0.06, 0.6, and 2.0 mg/kg with RSD of 0.3% to 7.8% (n = 5) for intra-day
      precision and 1.2% to 7.6% (n = 5) for inter-day precision. The LODGS and LOQGS
      for 14 PAEs were between 0.4 and 10.0 MUg/kg and 0.5 and 20.0 MUg/kg,
      respectively. Analysis of 32 commercial GS samples revealed that dimethyl-,
      diethyl-, diisobutyl-, dibutyl-, and di- (2-ethylhexyl) phthalate esters were
      detected in all of the analytes. In addition, content-color scale model was
      applied to visualize the concentration differences of PAEs in real GS samples.
      Principal component analysis of PAEs revealed that the GS samples did not have a
      distinctive cluster based on their geographic origins. The established method was
      proven to be simple, accurate, and effective for analysis of PAEs in GS, which
      might also be applied for analysis of PAEs in other matrices. PRACTICAL
      APPLICATION: A modified QuEChERS-based GC-MS method was developed for the
      determination of phthalate esters (PAEs) in grain sorghum (GS). The ubiquitous
      presence of PAEs can migrate into GS. Therefore, evaluation of the total content
      of PAEs in GS is helpful to understand its impact of overall pollution level on
      other foods. This study has provided some basic information in terms of the
      content and contamination of PAEs in GS, which is helpful to establish relevant
      standards and risk assessment of GS for the government.

PMID- 29577292
TI  - Consequences of electroshock-induced narcosis in fish muscle: from mitochondria
      to swim performance.
AB  - Adult zebrafish Danio rerio were exposed to an electric shock of 3 V and 1A for 5
      s delivered by field backpack electrofishing gear, to induce a taxis followed by
      a narcosis. The effect of such electric shock was investigated on both the
      individual performances (swimming capacities and costs of transport) and at
      cellular and mitochondrial levels (oxygen consumption and oxidative balance). The
      observed survival rate was very high (96.8%) independent of swimming speed (up to
      10 body length s-1 ). The results showed no effect of the treatment on the
      metabolism and cost of transport of the fish. Nor did the electroshock trigger
      any changes on muscular oxidative balance and bioenergetics even if red muscle
      fibres were more oxidative than white muscle. Phosphorylating respiration rates
      rose between (mean 1 s.e.) 11.16 +/- 1.36 pmol O2 s-1  mg-1 and 15.63 +/- 1.60
      pmol O2 s-1  mg-1 for red muscle fibres whereas phosphorylating respiration rates
      only reached 8.73 +/- 1.27 pmol O2 s-1  mg-1 in white muscle. Such an absence of
      detectable physiological consequences after electro-induced narcosis both at
      organismal and cellular scales indicate that this capture method has no apparent
      negative post-shock performance under the conditions of this study.

PMID- 29577293
TI  - Evaluation of Enzymatically Modified Soy Protein Isolate Film Forming Solution
      and Film at Different Manufacturing Conditions.
AB  - : The effects of transglutaminase on soy protein isolate (SPI) film forming
      solution and films were investigated by rheological behavior and physicochemical
      properties based on different manufacturing conditions (enzyme treatments, enzyme
      incubation times, and protein denaturation temperatures). Enzymatic crosslinking
      reaction and changes in molecular weight distribution were confirmed by viscosity
      measurement and SDS-PAGE, respectively, compared to 2 controls: the nonenzyme
      treated and the deactivated enzyme treated. Films treated with both the enzyme
      and the deactivated enzyme showed significant increase in tensile strength (TS),
      percent elongation (%E), and initial contact angle of films compared to the
      nonenzyme control film due to the bulk stabilizers in the commercial enzyme.
      Water absorption property, protein solubility, Fourier transform infrared (FTIR)
      and X-ray diffraction (XRD) spectroscopy revealed that enzyme treated SPI film
      matrix in the molecular structure level, resulted in the changes in
      physicochemical properties. Based on our observation, the enzymatic treatment at
      appropriate conditions is a practical and feasible way to control the physical
      properties of protein based biopolymeric film for many different scientific and
      industrial areas. PRACTICAL APPLICATION: Enzymes can make bridges selectively
      among different amino acids in the structure of protein matrix. Therefore,
      protein network is changed after enzyme treatment. The behavior of biopolymeric
      materials is dependent on the network structure to be suitable in different
      applications such as bioplastics applied in food and pharmaceutical products. In
      the current research, transglutaminase, as an enzyme, applied in soy protein
      matrix in different types of forms, activated and deactivated, and different
      preparation conditions to investigate its effects on different properties of the
      new bioplastic film.

PMID- 29577294
TI  - Caffeine Extraction from Raw and Roasted Coffee Beans.
AB  - : Coffee is a stimulant, psychoactive, popular daily beverage, and its caffeine
      affects human physiological health and behavior. These important issues prompted
      us to study caffeine extraction from both the raw and roasted coffee beans of 3
      types at different temperatures. A hemispheric model is developed to simulate the
      extraction process of the caffeine from the coffee beans of hemisphere is
      proposed. The experimental data are in good agreement with the predicted model.
      The effective diffusivities of caffeine in both the raw and roasted beans
      increase with temperature in all 3 types. An incubation period, decreasing with
      increasing temperature, is observed in all samples studied. Caffeine extraction
      in roasted beans is more rapid than that for the raw beans and the time
      difference is significant at low temperatures. In both the raw and roasted
      samples, caffeine diffusion in the raw beans and the incubation behavior are
      thermally activated processes. Single activation energies are obtained for
      diffusion within the extraction temperature range for all beans tested with the
      exception of one type of the coffee beans, Mandheling, which exhibits 2
      activation energies in raw samples. The surface energies of the epidermis of the
      raw beans and roasted beans obtained from the contact angle measurements are used
      to interpret the difference of incubation periods. PRACTICAL APPLICATION: This
      study has a potential application to the decaffeinated coffee industry.Caffeine
      affects human physiological health and behavior so that caffeine extraction from
      coffee beans of different types at different temperatures is important for
      product refining and customers.

PMID- 29577295
TI  - UHPLC/MS Identifying Potent alpha-glucosidase Inhibitors of Grape Pomace via
      Enzyme Immobilized Method.
AB  - : alpha-Glucosidases have been a major target in controlling and managing
      postprandial blood glucose and therefore diabetes treatment. This study aims to
      further identify and purify active compounds from the most active ethyl acetate
      fraction collected previously in Tinta Cao grape pomace extract (TCEE) using a
      newly developed and highly effective immobilization method, including obtaining
      compounds previously shown to inhibit the enzyme. Purification used crosslinked
      chitosan beads with alpha-glucosidases bound to polymer, which acted as
      immobilized enzyme vehicle to collect inhibitors. Compounds absorbed into the
      beads were eluded using methanol, where collected fraction was subjected to UHPLC
      MS analysis to identify active compounds. Results presented 5 major compounds:
      viniferifuran (amurensin H), p-coumaroyl-6-O-D-glucopyranoside, p-coumaroyl-6-O
      hexoside, (epi)catechin-hexoside, 10-carboxyl-pyranopeonidin 3-O-(6''-O-p
      coumaroyl)-glucoside. These findings indicated the particular molecules can be
      utilized as potent alpha-glucosidases inhibitors, and may be further tested for
      postprandial glucose control. PRACTICAL APPLICATION: A potential approach
      enriched and identified alpha-glucosidase inhibitors of grape pomace. Set-up of
      UHPLC/MS detection and identification of active compounds provide qualify
      assessment in developing grape pomace extract into potent dietary supplement and
      new drug for diabetes.

PMID- 29577296
TI  - Oral prebiotics and the influence of environmental conditions in vitro.
AB  - BACKGROUND: Only recently the concept of prebiotics has been introduced in oral
      health. Few potential oral prebiotics have already been identified in dual
      species competition assays, showing a stimulatory effect on beneficial bacteria
      and by this suppressing the outgrowth of pathogenic species. This study aimed to
      validate the effect of previously identified potential prebiotic substrates on
      multispecies cultures by shifting the biofilm composition towards a more
      beneficial species dominated microbiota. METHODS: A chemostat culture containing
      14 model oral bacterial species was used to grow biofilms for 24 hours which
      subsequently were treated with prebiotic solutions three times a day for 3
      consecutive days. Further the influence of environmental factors such as pH,
      nutrient availability, oxygen concentration and prebiotic dose on the efficacy of
      the prebiotic substances was investigated. RESULTS: Three potential prebiotic
      substrates N-acetyl-D-mannosamine, succinic acid and Met-Pro were able to bring
      the beneficial proportion to > 95%. While the pH of the prebiotic solution did
      not have an influence on the prebiotic effect, the interplay of nutrient
      availability, oxygen concentration and prebiotic treatment resulted in
      significant changes of the microbial composition identifying N-acetyl-D
      mannosamine as the most promising oral prebiotic substrate. Showing a clear dose
      dependent effect, concentrations of N-acetyl-D-mannosamine of 1.0 and 1.5 M
      resulted in a biofilm composition of 97% beneficial species. CONCLUSION:
      Introducing the prebiotic concept in oral health might reveal a valid approach
      for treatment and prevention of oral diseases and promote oral health.

PMID- 29577297
TI  - Aristotle's golden mean and the importance of bipolarity for personality models:
      A commentary on "Personality traits and maladaptivity: Unipolarity versus
      bipolarity".

PMID- 29577298
TI  - Individual self > relational self > collective self-But why? Processes driving
      the self-hierarchy in self- and person perception.
AB  - OBJECTIVE: The self has three parts: individual, relational, and collective.
      Typically, people personally value their individual self most, their relational
      self less, and their collective self least. This self-hierarchy is consequential,
      but underlying processes have remained unknown. Here, we propose two process
      accounts. The content account draws upon selves' agentic-communal content,
      explaining why the individual self is preferred most. The teleology account draws
      upon selves' instrumentality for becoming one's personal ideal, explaining why
      the collective self is preferred least. METHOD: In Study 1 (N = 200, 45% female,
      Mage  = 32.9 years, 79% Caucasian), participants listed characteristics of their
      three selves (individual, relational, collective) and evaluated those
      characteristics in seven preference tasks. Additionally, we analyzed the
      characteristics' agentic-communal content, and participants rated their
      characteristics' teleological instrumentality. Study 2 (N = 396, 55% female, Mage
      = 34.5 years, 76% Caucasian) used identical methodology and featured an
      additional condition, where participants evaluated the selves of a friend.
      RESULTS: Study 1 reconfirmed the self-hierarchy and supported both process
      accounts. Study 2 replicated and extended findings. As hypothesized, when people
      evaluate others' selves, a different self-hierarchy emerges (relational >
      individual > collective). CONCLUSIONS: This research pioneers process-driven
      explanations for the self-hierarchy, establishing why people prefer different
      self-parts in themselves than in others.

PMID- 29577299
TI  - Amplification and adaptation of centromeric repeats in polyploid switchgrass
      species.
AB  - Centromeres in most higher eukaryotes are composed of long arrays of satellite
      repeats from a single satellite repeat family. Why centromeres are dominated by a
      single satellite repeat and how the satellite repeats originate and evolve are
      among the most intriguing and long-standing questions in centromere biology. We
      identified eight satellite repeats in the centromeres of tetraploid switchgrass
      (Panicum virgatum). Seven repeats showed characteristics associated with
      classical centromeric repeats with monomeric lengths ranging from 166 to 187 bp.
      Interestingly, these repeats share an 80-bp DNA motif. We demonstrate that this
      80-bp motif may dictate translational and rotational phasing of the centromeric
      repeats with the cenH3 nucleosomes. The sequence of the last centromeric repeat,
      Pv156, is identical to the 5S ribosomal RNA genes. We demonstrate that a 5S
      ribosomal RNA gene array was recruited to be the functional centromere for one of
      the switchgrass chromosomes. Our findings reveal that certain types of satellite
      repeats, which are associated with unique sequence features and are composed of
      monomers in mono-nucleosomal length, are favorable for centromeres. Centromeric
      repeats may undergo dynamic amplification and adaptation before the centromeres
      in the same species become dominated by the best adapted satellite repeat.

PMID- 29577300
TI  - Prevalence of Virulence Genes in Extended-Spectrum beta-lactamases (ESBLs)
      Producing Salmonella in Retail Raw Chicken in China.
AB  - Extended-spectrum beta-lactamases (ESBLs)-producing Salmonella is a tremendous
      hazard to food safety and public health. The objective of this study was to
      determine the prevalence of 30 virulence genes (avrA, sipA, sseC, marT, rhuM,
      siiE, pipA, pipD, envR, gogB, gtgA, sodC1, sseI, irsA, sopE2, spvC, rck, spvR,
      fhuA, msgA, pagK, srfj, stkc, fimA, lpfD, pefA, stcC, steB, stjB, and tcfA) in
      156 ESBLs-producing Salmonella isolates that belonged to 21 serotypes. These
      isolates were recovered from retail raw chicken samples collected from 5
      provinces and 2 national cities in China between 2007 and 2012. The results
      indicated that 154 (98.7%) ESBLs-producing Salmonella isolates carried at least 1
      virulence gene, 138 (88.5%) simultaneously carried at least 5 virulence genes,
      107 (68.6%) carried 10 or more, and 20 (12.8%) carried 15 or more virulence
      genes. The most frequently detected virulence genes were marT (n = 127, 81.4%),
      siiE (n = 126, 80.8%), msgA (n = 121, 77.6%), and sipA (n = 121, 77.6%).
      Significant difference was identified between detection percentages of virulence
      genes of rhuM, pipD, envR, sopE2, pagK, lpfD, steB, and stjB in S. Indiana, S.
      Thompson, S. Enteritidis, S. Typhimurium, S. Shubra, S. Edinburg, and S. Agona
      isolates. Distribution of virulence genes were significantly influenced by
      sampling districts (P < 0.01), especially for sodC1 and pipD, and then were msgA
      and sopE2. The heatmap showed the frequencies of virulence genes in ESBLs
      producing isolates from retail chickens in southern, central, and northern
      regions of China were completely different from each other. Based on our
      findings, ESBLs-producing Salmonella of retail chicken origin were common
      carriers of multiple virulence genes and were regionally distributed.

PMID- 29577301
TI  - Effect of Different Heat Treatments on In Vitro Digestion of Egg White Proteins
      and Identification of Bioactive Peptides in Digested Products.
AB  - : Chicken eggs are ingested by people after a series of processes, but to date,
      only a few studies have explored the nutrient variations caused by different heat
      treatments. In this work, the impacts of different heat treatments (4, 56, 65,
      and 100  degrees C on the in vitro digestibility of egg white proteins were
      investigated by hydrolysis with pepsin or pepsin + pancreatin to simulate human
      gastrointestinal digestion, and the digested products were identified using Nano
      LC-ESI-MS/MS. Egg white proteins treated at 65  degrees C had the highest in
      vitro pepsin digestibility value whereas the pepsin + pancreatin digestibility
      increased significantly (P < 0.05) as the cooking temperature was raised. The
      molecular weight distribution of the digested products indicated that, when
      compared to pepsin-treated samples, pepsin + pancreatin-treated samples contained
      more low-molecular-weight peptides (m/z < 849.2) with higher signal intensities.
      The number of unique peptides identified in every digestion product showed a
      positive correlation with their in vitro digestibility. Additionally, bioactive
      peptides such as antioxidant, antimicrobial and antihypertensive peptides were
      found present in egg white digested products, especially in samples treated at 4
      and 100  degrees C. PRACTICAL APPLICATION: These findings may facilitate a better
      understanding of nutritive values of egg white proteins and their digested
      products under different cooking temperatures, such as antibacterial and
      antioxidant peptides identified in the digestion samples treated, respectively at
      4 and 100  degrees C. This study also provided information for improving the
      applications of eggs in the food industry as well as a theoretical basis for egg
      consumption.

PMID- 29577302
TI  - Flow cytometry for assessing the efficacy of interspecific gynogenesis induction
      in sturgeon.
AB  - The efficacy of ploidy analysis for separating progeny of Siberian sturgeon
      Acipenser baerii after induced gynogenesis was demonstrated using sperm of a
      paternal species differing in ploidy level from the maternal species. Gynogenesis
      was induced in tetraploid A. baerii with UV-C irradiated sperm from the diploid
      sterlet Acipenser ruthenus and vice-versa. The success of sperm UV irradiation
      and diploidy restoration by heat-shock was estimated based on the ploidy level of
      progeny, confirmed by microsatellite parentage assignment. Hatching rates of
      interspecific gynogenotes were comparable with rates reported for gynogenesis
      induction using sperm and eggs of the same species. Juvenile mortality was
      similar to that observed in the control hybrids. The efficiency and reliability
      of this method may foster its use for production of gynogenotes in aquaculture,
      potentially allowing interspecific gynogenesis to replace intraspecific.

PMID- 29577303
TI  - CT findings in Pneumocystis carinii pneumonia in five dogs.
AB  - Pneumocystis carinii pneumonia is a rare disease in dogs. It is primarily
      reported in cavalier King Charles spaniels and miniature dachshunds with
      suspected underlying immunodeficiency. This case series reports the findings in
      five dogs (four cavalier King Charles spaniels and one Bedlington terrier) with
      confirmed P. carinii pneumonia. Thoracic (CT) revealed ground glass opacity of
      the pulmonary parenchyma with a diffuse or multifocal distribution. The severity
      of this pattern was variable. Less consistent imaging findings included
      parenchymal bands, bronchial dilation and signs consistent with pulmonary
      hypertension. Four dogs recovered well with treatment and there was resolution of
      CT abnormalities in all dogs with follow-up.

PMID- 29577304
TI  - Plasticity of transcallosal pathways after stroke and their role in recovery.

PMID- 29577306
TI  - Clinical safety of percutaneous ultrasound-guided fine-needle aspiration of
      adrenal gland lesions in 19 dogs.
AB  - OBJECTIVE: To evaluate the safety of fine-needle aspiration of adrenal gland
      lesions in dogs and to characterise the risks in a subset of patients with
      cytologically or histopathologically diagnosed phaeochromocytoma. MATERIALS AND
      METHODS: Retrospective review of medical records of dogs that underwent
      percutaneous ultrasound-guided fine-needle aspiration of adrenal gland lesions
      between August 2014 and December 2016. Nineteen dogs were identified, with three
      undergoing bilateral adrenal gland aspiration and one dog undergoing aspiration
      twice, yielding 23 cytology samples in total. Data collected included signalment,
      concurrent medical conditions, current medications, blood pressure and heart rate
      before adrenal fine-needle aspiration, imaging characteristics of the adrenal
      gland lesions and any clinically apparent procedure-related complications.
      RESULTS: Phaeochromocytoma was diagnosed in nine of 19 dogs, including one dog
      with bilateral phaeochromocytoma. One dog developed ventricular tachycardia
      following aspiration of an adrenal gland lesion cytologically consistent with a
      phaeochromocytoma. CLINICAL SIGNIFICANCE: Percutaneous ultrasound-guided fine
      needle aspiration of adrenal gland lesions appears to be relatively safe, even in
      phaeochromocytoma, but further data are required to lend more weight to this
      finding. Minimally invasive aspirates could be considered as part of the
      diagnostic algorithm in the investigation of an incidentally detected adrenal
      gland lesion of uncertain clinical significance.

PMID- 29577305
TI  - Aberrant cortical excitability reflects the loss of hand dexterity in musician's
      dystonia.
AB  - KEY POINTS: Dystonia is a movement disorder characterized by abnormalities at
      multifaceted aspects of motor dexterity and neural functions. Evidence bridging
      between pathophysiology and movement abnormalities is limited. A novel finding
      was that in focal task-specific dystonia (FTSD), an aberrantly reduced inhibition
      at the motor cortex was related to the temporal imprecision of the dexterous
      finger movements, whereas an elevated facilitation was associated with an
      abnormally sluggish transition of finger movements from flexion to extension. We
      newly identified two sets of behavioural-physiological covariations as hallmarks
      of hand FTSD, which is clinically significant because these findings provide
      novel evidence connecting distinct types of malfunctions within the motor cortex
      at rest with distinct aspects of motor dexterity degradation in FTSD patients.
      ABSTRACT: Focal task-specific dystonia (FTSD) compromises dexterous movements. A
      proposed pathophysiological mechanism of FTSD involves malfunction of the motor
      cortex (M1). However, no evidence is yet available regarding whether and how
      malfunctions of M1 are responsible for the loss of motor dexterity. Here, we
      addressed this issue by assessing both M1 excitability and detailed movement
      parameters, as well as their relationships. Transcranial magnetic stimulation was
      applied over M1 in 20 pianists with FTSD, 20 healthy pianists and 20 non
      musicians. The patients demonstrated both reduced short-interval intracortical
      inhibition (SICI) and elevated intracortical facilitation (ICF) compared with the
      healthy controls. This indicates that the abnormal cortical excitability reflects
      pathophysiology but not current skills. Hand motor dexterity was evaluated by
      position sensors during piano playing at two tempi. The patients showed delayed
      transition from finger flexion to extension at the fastest tempo and greater
      timing variability of the finger movements. Furthermore, multivariate analyses
      identified distinct sets of covariation between cortical excitability and
      dexterity measures. Namely, the SICI measure and ICF measure were associated with
      the temporal variability of the movements and the quickness of the transition
      from flexion to extension, respectively. Specifically, the reduced inhibition and
      elevated facilitation at M1 in pianists was related to the temporal imprecision
      and impairment of quick transitions in the sequential finger movements. The
      present study provides novel evidence associating M1 malfunctions with dexterity
      loss.

PMID- 29577307
TI  - Importance of weather monitoring for agricultural decision-making - an
      exploratory behavioral study for Oklahoma Mesonet.
AB  - BACKGROUND: The Oklahoma Mesonet (the statewide environmental and weather
      monitoring network) has monitored changes in weather patterns since 1994 to
      provide accurate and timely mesoscale weather information to farmers and other
      groups. Studies are still scarce that would quantitatively assess farmers'
      perceptions about the value of the Oklahoma Mesonet contributions to agricultural
      operations, profitability of land management, and decision making. This paper
      aims to analyze those questions by means of an exploratory empirical study in
      Oklahoma for two groups of Mesonet users and non-users. RESULTS: Familiarity with
      and application of Mesonet information determines farmers' profitability
      assessments and decision making. Farmers' perceptions are also influenced by the
      degree of previous exposure to weather-related losses. The median estimate of the
      economic value of Mesonet information is $1000 per year. Mesonet users perceive
      higher profitability from the application of Mesonet data at 7.6/10, whereas
      Mesonet non-users provided an average assessment of 2.6/10. CONCLUSIONS:
      Consistent use of Mesonet information results in a higher assessment of the
      importance of Mesonet. This research provides some initial insights into farmers'
      perceptions about the value of Oklahoma Mesonet information, which could guide
      stakeholders in developing measures to better serve farmers with environmental
      monitoring data for improved farm decisions. (c) 2018 Society of Chemical
      Industry.

PMID- 29577308
TI  - The final chapter of Vygotsky's Thinking and Speech: A reader's guide.
AB  - The seventh and last chapter of Vygotsky's Thinking and Speech (1934) is
      generally considered as his final word in psychology. It is a long chapter with a
      complex argumentative structure in which Vygotsky gives his view on the
      relationship between thinking and speech. Vygotsky's biographers have stated that
      the chapter was dictated in the final months of Vygotsky's life when his health
      was rapidly deteriorating. Although the chapter is famous, its structure has
      never been analyzed in any detail. In the present article we reveal its
      rhetorical structure and show how Vygotsky drew on many hitherto unrevealed
      sources to convince the reader of his viewpoint.

PMID- 29577309
TI  - Determination of changes in the concentration and distribution of elements within
      olive drupes (cv. Leccino) from Se biofortified plants, using laser ablation
      inductively coupled plasma mass spectrometry.
AB  - BACKGROUND: Biofortification of food crops has been used to increase the intake
      of Se in the human diet, even though this may change the concentration of other
      elements and modify the nutritional properties of the enriched food. Selenium
      biofortification programs should include routine assessment of the overall
      mineral composition of enriched plants. RESULTS: Laser ablation inductively
      coupled plasma mass spectrometry (LA ICP-MS) was used for the assessment of
      mineral composition of table olives. Olive trees were fertilized with sodium
      selenate before flowering. At harvest, the edible parts of drupes proved to be
      significantly enriched in Se, delivering 6.1 MUg g-1 (39% of the RDA for five
      olives). Such enrichment was followed by significant changes in the
      concentrations of B, Mg, K, Cr, Mn, Fe and Cu in edible parts, which are
      discussed for their impact on food quality. CONCLUSION: The biofortification of
      olive plants has allowed the enrichment of fruits with selenium. Enrichment with
      selenium has caused an increase in the concentration of other elements, which can
      change the nutritional quality of the drupes. The analytical technique used well
      as a valuable tool for routinely determining the chemical composition of all
      fruit parts. (c) 2018 Society of Chemical Industry.

PMID- 29577310
TI  - Quantitative analysis of amino acids in human and bovine colostrum milk samples
      through iTRAQ labeling.
AB  - BACKGROUND: The types and quantity of proteins vary widely between bovine and
      human milk, with corresponding differences in free and hydrolytic amino acids. In
      this study, the free and hydrolytic amino acids of bovine and human colostrum
      were for the first time qualitatively and quantitatively determined using
      isobaric tags for relative and absolute quantification technology combined with
      liquid chromatography tandem mass spectrometry detection. RESULTS: Total free
      amino acid content was 0.32 g L-1 and 0.63 g L-1 in bovine and human colostrum
      respectively, with free amino acid content in human colostrum twice that of
      bovine colostrum. However, total hydrolytic amino acid content was 4.2 g L-1 and
      2.2 g L-1 in bovine and human colostrum respectively. We found that the
      hydrolytic amino acid content in bovine colostrum was higher than that in human
      colostrum; however, the amount of free amino acids and the overall amino acid
      content in human colostrum were respectively substantially higher and more varied
      than in bovine colostrum. CONCLUSION: Our findings revealed differences between
      bovine and human colostrum, with these data providing the basis for further
      research into amino acid metabolomics and infant formula. (c) 2018 Society of
      Chemical Industry.

PMID- 29577311
TI  - Analysis of the cocobiota and metabolites of Moniliophthora perniciosa-resistant
      Theobroma cacao beans during spontaneous fermentation in southern Brazil.
AB  - BACKGROUND: Cocoa bean fermentation is a spontaneous process involving a
      succession of microbial activities, yeasts, lactic acid, and acetic acid
      bacteria. The spontaneous fermentation of cocoa beans by Theobroma cacao TSH565
      clonal variety, a highly productive hybrid resistant to Moniliophthora perniciosa
      and Phytophthora spp., was investigated. The natural cocobiota involved in the
      spontaneous fermentation of this hybrid in southern Brazil, was investigated by
      using both a culture-dependent microbiological analysis and a molecular analysis.
      The changes in the physicochemical characteristics and the kinetics of substrate
      utilization and metabolite production during fermentation were also evaluated.
      RESULTS: Yeasts (178) and bacteria (244) isolated during fermentation were
      identified by partial sequencing of the ITS and 16S rDNAs, respectively. After
      144 h of fermentation, the indigenous yeast community was composed of
      Hanseniaspora spp., Saccharomyces spp., and Pichia spp. The bacterial population
      comprised Lactococcus spp., Staphylococcus spp., Acetobacter spp. and
      Lactobacilli strains. The kinetics of substrate transformation reflected the
      dynamic composition of the cocobiota. Substrates such as glucose, fructose,
      sucrose, and citric acid, present at the beginning of fermentation, were
      metabolized to produce ethanol, acetic acid, and lactic acid. CONCLUSION: The
      results described here provide new insights into microbial diversity in cocoa
      bean-pulp mass fermentation and the kinetics of metabolites synthesis, and pave
      the way for the selection of starter cultures to increase efficiency and
      consistency to obtain homogeneous and best quality cocoa products. (c) 2018
      Society of Chemical Industry.

PMID- 29577312
TI  - Rapid prediction of deoxynivalenol contamination in wheat bran by MOS-based
      electronic nose and characterization of the relevant pattern of volatile
      compounds.
AB  - BACKGROUND: Deoxynivalenol (DON) is a mycotoxin, mainly produced by Fusarium sp.,
      most frequently occurring in cereals and cereal-based products. Wheat bran refers
      to the outer layers of the kernel, which has a high risk of damage due to
      chemical hazards, including mycotoxins. Rapid methods for DON detection in wheat
      bran are required. RESULTS: A rapid screening method using an electronic nose (e
      nose), based on metal oxide semiconductor sensors, has been developed to
      distinguish wheat bran samples with different levels of DON contamination. A
      total of 470 naturally contaminated wheat bran samples were analyzed by e-nose
      analysis. Wheat bran samples were divided in two contamination classes: class A
      ([DON] <= 400 ug kg-1 , 225 samples) and class B ([DON] > 400 ug kg-1 , 245
      samples). Discriminant function analysis (DFA) classified wheat bran samples with
      good mean recognizability in terms of both calibration (92%) and validation
      (89%). A pattern of 17 volatile compounds of wheat bran samples that were
      associated (positively or negatively) with DON content was also characterized by
      HS-SPME/GC-MS. CONCLUSIONS: These results indicate that the e-nose method could
      be a useful tool for high-throughput screening of DON-contaminated wheat bran
      samples for their classification as acceptable / rejectable at contamination
      levels close to the EU maximum limit for DON, reducing the number of samples to
      be analyzed with a confirmatory method. (c) 2018 Society of Chemical Industry.

PMID- 29577313
TI  - The Impact of the Roast Levels of Coffee Extracts on their Potential Anticancer
      Activities.
AB  - : Coffee is one of the most widely consumed beverages in the world and contains
      numerous phytochemicals that are beneficial to consumer health. The phytochemical
      profile of coffee, however, can be affected by the roast level. In this study, we
      compared the effect of roasting level on the growth inhibitory activity of HT-29
      (colon) and SCC-25 (oral) cancer cell lines. The different roasting stages
      selected for this study were green, cinnamon/blonde, city/medium, full
      city/medium-dark, and full city plus/dark. Cancer cells were treated with various
      concentrations of coffee extracts for 72 hr. Cell viability was quantified using
      the thiazolyl blue tetrazolium bromide assay. It was found that the lighter roast
      extracts, Cinnamon in particular, reduced cell growth more than darker roast
      extracts. The Cinnamon extract had the greatest amount of total phenolic content
      and antioxidant activity. Relative levels of gallic, caffeic, and chlorogenic
      acid in the extracts were also compared. The Cinnamon coffee extract had the
      highest levels of gallic and caffeic acids, which have both been widely-regarded
      as bioactive phytochemicals. In conclusion, the consumption of lighter roasted
      coffee, may contribute to the prevention of certain types of cancer such as oral
      and colon. PRACTICAL APPLICATION: Chemical compounds in coffee may reduce the
      risk for certain types of cancers. These compounds may be particularly abundant
      in lighter roasted coffee. Therefore, lighter roasted coffee could contribute to
      the prevention of cancer through a healthy diet.

PMID- 29577315
TI  - The RecQ-like helicase HRQ1 is involved in DNA crosslink repair in Arabidopsis in
      a common pathway with the Fanconi anemia-associated nuclease FAN1 and the
      postreplicative repair ATPase RAD5A.
AB  - RecQ helicases are important caretakers of genome stability and occur in varying
      copy numbers in different eukaryotes. Subsets of RecQ paralogs are involved in
      DNA crosslink (CL) repair. The orthologs of AtRECQ2, AtRECQ3 and AtHRQ1, HsWRN,
      DmRECQ5 and ScHRQ1 participate in CL repair in their respective organisms, and we
      aimed to define the function of these helicases for plants. We obtained
      Arabidopsis mutants of the three RecQ helicases and determined their sensitivity
      against CL agents in single- and double-mutant analyses. Only Athrq1, but not
      Atrecq2 and Atrecq3, mutants proved to be sensitive to intra- and interstrand
      crosslinking agents. AtHRQ1 is specifically involved in the repair of replicative
      damage induced by CL agents. It shares pathways with the Fanconi anemia-related
      endonuclease FAN1 but not with the endonuclease MUS81. Most surprisingly, AtHRQ1
      is epistatic to the ATPase RAD5A for intra- as well as interstrand CL repair. We
      conclude that, as in fungi, AtHRQ1 has a conserved function in DNA excision
      repair. Additionally, HRQ1 not only shares pathways with the Fanconi anemia
      repair factors, but in contrast to fungi also seems to act in a common pathway
      with postreplicative DNA repair.

PMID- 29577314
TI  - Effect of dietary processed sulfur supplementation on water-soluble flavor
      precursors, free amino acids, and taste characteristics of pork during
      refrigerated storage.
AB  - BACKGROUND: A total of 60 three-way crossbred (Landrace, Duroc, and Yorkshire)
      pigs were divided into two groups (processed sulfur-fed pigs (SFPs) and
      nonprocessed sulfur-fed pigs, (NSFPs)) and used to determine the effect of
      supplementation with 3 g kg-1 processed sulfur on water-soluble precursors, free
      amino acids, and taste of meat using an electronic tongue, during refrigerated
      storage. RESULTS: Glycogen and glucose levels of SFP were significantly higher
      than in NSFPs. Glycogen levels decreased and glucose levels increased during
      storage (P < 0.001). The pH and moisture content of SFPs were higher than in
      NSFPs. Inosine of SFPs was higher than in NSFPs (P < 0.05). Hence, umami and
      richness tastes of SFPs were higher than in NSFPs and increased during storage.
      The total free amino acid content of both groups was not different, although it
      increased during storage (P < 0.001). The umami taste of water-soluble precursors
      was improved in meat derived from SFPs during refrigeration. CONCLUSION: The
      storage time and dietary supplementation with processed sulfur increased the
      taste components of meat. Application of an electronic tongue system can be used
      to distinguish the taste characteristics of different types of pork, based on
      differential supplementation and aging. (c) 2018 Society of Chemical Industry.

PMID- 29577316
TI  - Plastid genomes hit the big time.

PMID- 29577317
TI  - Arabidopsis thaliana SOBER1 (SUPPRESSOR OF AVRBST-ELICITED RESISTANCE 1)
      suppresses plant immunity triggered by multiple bacterial acetyltransferase
      effectors.
AB  - Plants evolved disease resistance (R) proteins that recognize corresponding
      pathogen effectors and activate effector-triggered immunity (ETI). However, it is
      largely unknown why, in some cases, a suppressor of ETI exists in plants.
      Arabidopsis SOBER1 (Suppressor of AvrBsT-elicited Resistance 1) was identified
      previously as a suppressor of Xanthomonas acetyltransferase effector AvrBsT
      triggered immunity. Nevertheless, the extent to which SOBER1 suppresses ETI is
      unclear. Here, we identified SOBER1 as a suppressor of Pseudomonas
      acetyltransferase effector HopZ5-triggered immunity in Arabidopsis using
      recombinant inbred lines. Further analysis showed that SOBER1 suppresses immunity
      triggered by multiple bacterial acetyltransferases. Interestingly, SOBER1
      interferes with the immunity signalling activated by some but not all tested
      acetyltransferase effectors, indicating that SOBER1 might target components that
      are shared between several ETI pathways.

PMID- 29577318
TI  - Mental disorders in chronic obstructive pulmonary diseases.
AB  - PURPOSE: Anxiety and depression are underdiagnosed in chronic obstructive
      pulmonary disease (COPD) patients. Few studies have tried to identify their
      association with hospitalization (severe exacerbation). The objective of this
      study was to determine whether the anxiety/depression was associated with severe
      exacerbation. DESIGN AND METHODS: A prospective cohort study, based on a sample
      of 512 patients diagnosed with COPD originating from primary care in a rural area
      in Lleida (Spain) and monitored between November 1, 2012 and October 31, 2014.
      For each patient, variables of interest were recorded; they were administered the
      HADS (Hospital Anxiety and Depression Scale) test to determine the possible
      presence of anxiety/depression, and its association with severe exacerbation was
      analyzed using a logistic regression model. FINDINGS: Initially, the prevalence
      of anxiety/depression was 15.6%. The incidence of global hospitalization in the
      first year was 8.2% and 11.3% in the second year. In patients with
      anxiety/depression, it increased to 17.5% in the first year and 18.8% in the
      second year. In the multivariate regression model, the diagnosis of
      anxiety/depression almost doubled the risk of hospitalization (OR = 1.94) (p <
      .041). PRACTICE IMPLICATIONS: Anxiety and depression are associated with an
      increased risk of hospitalization. Intervention studies are needed to evaluate
      the effects of anxiety/depression in the hospitalization.

PMID- 29577319
TI  - El Nino drought increased canopy turnover in Amazon forests.
AB  - Amazon droughts, including the 2015-2016 El Nino, may reduce forest net primary
      productivity and increase canopy tree mortality, thereby altering both the short-
      and the long-term net forest carbon balance. Given the broad extent of drought
      impacts, inventory plots or eddy flux towers may not capture regional variability
      in forest response to drought. We used multi-temporal airborne Lidar data and
      field measurements of coarse woody debris to estimate patterns of canopy turnover
      and associated carbon losses in intact and fragmented forests in the central
      Brazilian Amazon between 2013-2014 and 2014-2016. Average annualized canopy
      turnover rates increased by 65% during the drought period in both intact and
      fragmented forests. The average size and height of turnover events was similar
      for both time intervals, in contrast to expectations that the 2015-2016 El Nino
      drought would disproportionally affect large trees. Lidar-biomass relationships
      between canopy turnover and field measurements of coarse woody debris were modest
      (R2  ~ 0.3), given similar coarse woody debris production and Lidar-derived
      changes in canopy volume from single tree and multiple branch fall events. Our
      findings suggest that El Nino conditions accelerated canopy turnover in central
      Amazon forests, increasing coarse woody debris production by 62% to 1.22 Mg C ha
      1  yr-1 in drought years .

PMID- 29577320
TI  - Correlated seed failure as an environmental veto to synchronize reproduction of
      masting plants.
AB  - Variable, synchronized seed production, called masting, is a widespread
      reproductive strategy in plants. Resource dynamics, pollination success, and, as
      described here, environmental veto are possible proximate mechanisms driving
      masting. We explored the environmental veto hypothesis, which assumes that
      reproductive synchrony is driven by external factors preventing reproduction in
      some years, by extending the resource budget model of masting with correlated
      reproductive failure. We ran this model across its parameter space to explore how
      key parameters interact to drive seeding dynamics. Next, we parameterized the
      model based on 16 yr of seed production data for populations of red (Quercus
      rubra) and white (Quercus alba) oaks. We used these empirical models to simulate
      seeding dynamics, and compared simulated time series with patterns observed in
      the field. Simulations showed that resource dynamics and reproduction failure can
      produce masting even in the absence of pollen coupling. In concordance with this,
      in both oaks, among-year variation in resource gain and correlated reproductive
      failure were necessary and sufficient to reproduce masting, whereas pollen
      coupling, although present, was not necessary. Reproductive failure caused by
      environmental veto may drive large-scale synchronization without density
      dependent pollen limitation. Reproduction-inhibiting weather events are prevalent
      in ecosystems, making described mechanisms likely to operate in many systems.

PMID- 29577321
TI  - Is mepivacaine as effective as lidocaine during inferior alveolar nerve blocks in
      patients with symptomatic irreversible pulpitis? A systematic review and meta
      analysis.
AB  - This study aimed to compare the effectiveness of mepivacaine and lidocaine for
      pulpal anaesthesia and pain control when administered via an inferior alveolar
      nerve block during the root canal treatment of mandibular molars in patients with
      symptomatic irreversible pulpitis. A research protocol was developed and
      registered in PROSPERO. The systematic search was conducted during May 2017 in
      eight databases. The studies were selected based on inclusion and exclusion
      criteria. Two examiners analysed the sample independently, decided the
      eligibility for inclusion and classified the articles according to their quality.
      Statistical analysis was performed with Mantel-Haenszel and I-square (I2 ) tests
      considering a confidence interval of 95%. The initial sample consisted of 1130
      articles, out of which four were eligible. The articles were published between
      1993 and 2016. For both pulpal anaesthesia and pain control, there was no
      significant difference between mepivacaine and lidocaine (P = 0.843, I2  = 0%,
      and P = 0.183, I2  = 21.1%, respectively). Mepivacaine and lidocaine were
      similarly effective for pulpal anaesthesia and pain control after inferior
      alveolar nerve blocks for root canal treatment.

PMID- 29577322
TI  - Detecting oropharyngeal carcinoma using multispectral, narrow-band imaging and
      machine learning.
AB  - OBJECTIVE: To determine if multispectral narrow-band imaging (mNBI) can be used
      for automated, quantitative detection of oropharyngeal carcinoma (OPC). STUDY
      DESIGN: Prospective cohort study. METHODS: Multispectral narrow-band imaging and
      white light endoscopy (WLE) were used to examine the lymphoepithelial tissues of
      the oropharynx in a preliminary cohort of 30 patients (20 with biopsy-proven OPC,
      10 healthy). Low-level image features from five patients were then extracted to
      train naive Bayesian classifiers for healthy and malignant tissue. RESULTS:
      Tumors were classified by color features with 65.9% accuracy, 66.8% sensitivity,
      and 64.9% specificity under mNBI. In contrast, tumors were classified with 52.3%
      accuracy (P = 0.0108), 44.8% sensitivity (P = 0.0793), and 59.9% specificity (P =
      0.312) under WLE. Receiver operating characteristic analysis yielded areas under
      the curve (AUC) of 72.3% and 54.6% for classification under mNBI and WLE,
      respectively (P = 0.00168). For classification by both color and texture
      features, AUC under mNBI increased (80.1%, P = 0.00230) but did not improve under
      WLE (below 55% for both models, P = 0.180). Cross-validation with five folds
      yielded an AUC above 80% for both mNBI models and below 55% for both WLE models
      (P = 0.0000410 and 0.000116). CONCLUSION: Compared to WLE, mNBI significantly
      enhanced the performance of a naive Bayesian classifier trained on low-level
      image features of oropharyngeal mucosa. These findings suggest that automated
      clinical detection of OPC might be used to enhance surgical vision, improve early
      diagnosis, and allow for high-throughput screening. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 2514-2520, 2018.

PMID- 29577323
TI  - Key questions and challenges in angiosperm macroevolution.
AB  - Contents Summary 1170 I. Introduction 1170 II. Six key questions 1172 III. Three
      key challenges 1177 IV. Conclusions 1181 Acknowledgements 1182 References 1183
      SUMMARY: The origin and rapid diversification of angiosperms (flowering plants)
      represent one of the most intriguing topics in evolutionary biology. Despite
      considerable progress made in complementary fields over the last two decades
      (paleobotany, phylogenetics, ecology, evo-devo, genomics), many important
      questions remain. For instance, what has been the impact of mass extinctions on
      angiosperm diversification? Are the angiosperms an adaptive radiation? Has
      morphological evolution in angiosperms been gradual or pulsed? We propose that
      the recent and ongoing revolution in macroevolutionary methods provides an
      unprecedented opportunity to explore long-standing questions that probably hold
      important clues to understand present-day biodiversity. We present six key
      questions that explore the origin and diversification of angiosperms. We also
      identify three key challenges to address these questions: (1) the development of
      new integrative models that include diversification, multiple intrinsic and
      environmental traits, biogeography and the fossil record all at once, whilst
      accounting for sampling bias and heterogeneity of macroevolutionary processes
      through time and among lineages; (2) the need for large and standardized
      synthetic databases of morphological variation; and (3) continuous effort on
      sampling the fossil record, but with a revolution in current paleobotanical
      practice.

PMID- 29577324
TI  - Transfusion of autologous extracellular vesicles from stored red blood cells does
      not affect coagulation in a model of human endotoxemia.
AB  - BACKGROUND: Red blood cell (RBC) transfusion has been related to thromboembolic
      events. Microvesicles in the RBC product may support coagulation because they
      have procoagulant effects in vitro. We investigated whether transfusion of RBCs
      containing extracellular vesicles promotes coagulation in human recipients. As
      transfusion is mostly administered to ill patients, we used a model of
      endotoxemia. STUDY DESIGN AND METHODS: Eighteen healthy volunteers were
      randomized to receive either saline or fresh (2 days stored) or stored autologous
      (35 days stored) RBC transfusion (Dutch Trial Register: NTR4455). Two hours after
      infusion of lipopolysaccharide (LPS, from Escherichia coli, 2 ng/kg body weight),
      subjects received either saline or fresh or stored RBCs. Blood was sampled every
      2 hours up to 8 hours after LPS infusion. Vesicles were measured with a flow
      cytometer (A50-Micro, Apogee Flow Systems). RESULTS: LPS resulted in increased
      thrombin generation compared to baseline. During storage, the total number of
      extracellular vesicles increased from 1.4 * 108 /mL (interquartile range [IQR],
      8.3 * 107 -1.9 * 108 /mL) in the fresh product to 1.7 * 1010 /mL (IQR, 7.9 * 109 
      2.3 * 1010 /mL; p < 0.01) in the stored product (p < 0.001). Vesicles appeared to
      be mostly RBC derived. CONCLUSION: After transfusion, extracellular vesicles from
      stored RBC products, but not from fresh products, could be detected in the
      circulation of healthy volunteers. However, infusion of stored RBC extracellular
      vesicles did not augment thrombin generation compared to endotoxemic controls.
      Also, levels of d-dimer and thrombin-antithrombin complex were unaffected. In
      conclusion, transfusion of autologous RBCs containing high levels of
      extracellular vesicles does not enhance coagulation in human volunteers with
      endotoxemia.

PMID- 29577325
TI  - Increased transpiration is correlated with reduced boron deficiency symptoms in
      the maize tassel-less1 mutant.
AB  - Loss-of-function mutations of the tassel-less1 (tls1) gene in maize, which is the
      co-ortholog of the Arabidopsis boron (B) importer NIP5;1, leads to the loss of
      reproductive structures (tassels and ears). The tls1 phenotypes can be rescued by
      B supplementation in the field and in the greenhouse. As the rescue with B
      supplementation is variable in the field, we investigated additional abiotic
      factors, potentially causing this variation in controlled greenhouse conditions.
      We found that the B-dependent rescue of the tls1 mutant tassel phenotype was
      enhanced when plants were grown with a mix of high pressure sodium (HPS) and
      metal halide (MH) lamps. Normal and tls1 plants had a significant increase in
      transpiration and increased B content in the leaves in the greenhouse with the
      addition of MH lamps. Our findings imply that B transport to the shoot is
      enhanced through increased transpiration, which suggests that the xylem
      transpiration stream provides a significant supply of B in maize.

PMID- 29577326
TI  - A Feasibility Trial of Mental Health First Aid First Nations: Acceptability,
      Cultural Adaptation, and Preliminary Outcomes.
AB  - The Mental Health First Aid First Nations course was adapted from Mental Health
      First Aid Basic to create a community-based, culturally safe and relevant
      approach to promoting mental health literacy in First Nations contexts. Over 2.5
      days, the course aims to build community capacity by teaching individuals to
      recognize and respond to mental health crises. This feasibility trial utilized
      mixed methods to evaluate the acceptability, cultural adaptation, and preliminary
      effectiveness of MHFAFN. Our approach was grounded in community-based
      participatory research principles, emphasizing relationship-driven procedures to
      collecting data and choice for how participants shared their voices. Data
      included participant interviews (n = 89), and surveys (n = 91) from 10 groups in
      four provinces. Surveys contained open-ended questions, retrospective pre-post
      ratings, and a scenario. We utilized data from nine facilitator interviews and 24
      facilitator implementation surveys. The different lines of evidence converged to
      highlight strong acceptability, mixed reactions to the cultural adaptation, and
      gains in participants' knowledge, mental health first aid skill application,
      awareness, and self-efficacy, and reductions in stigma beliefs. Beyond promoting
      individual gains, the course served as a community-wide prevention approach by
      situating mental health in a colonial context and highlighting local resources
      and cultural strengths for promoting mental well-being.

PMID- 29577327
TI  - Gamma and infra-slow oscillations shape neuronal firing in the rat subcortical
      visual system.
AB  - KEY POINTS: Neuronal oscillations observed in sensory systems are physiological
      carriers of information about stimulus features. Rhythm in the infra-slow range,
      originating from the retina, was previously found in the firing of subcortical
      visual system nuclei involved in both image and non-image forming functions. The
      present study shows that the firing of neurons in the lateral geniculate nucleus
      is also governed by gamma oscillation (~35 Hz) time-locked to high phase of infra
      slow rhythm that codes the intensity of transient light stimulation. We show that
      both physiological rhythms are synchronized within and between ipsilateral nuclei
      of the subcortical visual system and are dependent on retinal activity. The
      present study shows that neurophysiological oscillations characterized by various
      frequencies not only coexist in the subcortical visual system, but also are
      subjected to complex interference and synchronization processes. ABSTRACT: The
      physiological function of rhythmic firing in the neuronal networks of sensory
      systems has been linked with information coding. Also, neuronal oscillations in
      different frequency bands often change as a signature of brain state or sensory
      processing. Infra-slow oscillation (ISO) in the neuronal firing dependent on the
      retinal network has been described previously in the structures of the
      subcortical visual system. In the present study, we show for the first time that
      firing of ISO neurons in the lateral geniculate nucleus is also characterized by
      a harmonic discharge pattern (i.e. action potentials are separated by the
      intervals governed by fundamental frequency in the gamma range: ~35 Hz). A
      similar phenomenon was recently described in the suprachiasmatic nuclei of the
      hypothalamus: the master biological clock. We found that both gamma and ISO
      rhythms were synchronized within and between ipsilateral nuclei of the
      subcortical visual system and were dependent on the retinal activity of the
      contralateral eye. These oscillatory patterns were differentially influenced by
      transient and prolonged light stimulation with respect to both frequency change
      direction and sustainability. The results of the present study show that the
      firing pattern of neurons in the subcortical visual system is shaped by
      oscillations from infra-slow and gamma frequency bands that are plausibly
      generated by the retinal network. Additionally, the results demonstrate that both
      rhythms are not a distinctive feature of image or non-image forming visual
      systems but, instead, they comprise two channels carrying distinctive properties
      of photic information.

PMID- 29577328
TI  - Calcium in drinking water: effect on iron stores in Danish blood donors-results
      from the Danish Blood Donor Study.
AB  - BACKGROUND: Studies confirm that calcium inhibits iron absorption. Danish tap
      water comes from groundwater, which contains varying amounts of calcium depending
      on the subsoil. We investigated the association of calcium in drinking water with
      iron levels in Danish blood donors. STUDY DESIGN AND METHODS: We used data on
      Danish blood donors including dietary and lifestyle habits, blood donation
      history, and physiologic characteristics including measures of ferritin levels
      along with information on area of residence from The Danish Blood Donor Study.
      Data on calcium levels in groundwater ("water hardness") were obtained through
      the Geological Survey of Denmark and Greenland. We performed multiple linear and
      logistic regression analyses to evaluate the effect of water hardness on ferritin
      levels and risk of having iron deficiency (defined as ferritin levels <15 ng/mL),
      stratified by sex. RESULTS: There was a significant negative association between
      water hardness and ferritin levels in both men and women. Risk of iron deficiency
      was correspondingly increased in both men (odds ratio [OR], 1.55; 95% confidence
      interval [CI], 1.14-2.12) and women (OR, 1.20; 95% CI, 1.03-1.40) with increasing
      water hardness. In analyses restricted to individuals who received supplemental
      iron tablets no significant association between groundwater hardness and ferritin
      levels was observed. CONCLUSIONS: As measured by ferritin levels, residential
      drinking water calcium content is associated with blood donors- iron levels and
      risk of iron deficiency. However, effect sizes are small.

PMID- 29577329
TI  - Who victimizes whom and who defends whom? A multivariate social network analysis
      of victimization, aggression, and defending in early childhood.
AB  - The aim of this research was to investigate the interplay between victim
      aggressor relationships and defending relationships in early childhood to test
      the proposition that young aggressors are less selective than older children in
      their choice of vulnerable targets. Cross-sectional multivariate statistical
      social network analyses (Exponential Random Graph Models) for a sample of 177
      preschoolers from seven classes, 5- to 7-years-old, revealed that boys were more
      aggressive than girls, toward both boys and girls, whereas defending
      relationships were most often same-sex. There was significant reciprocity in
      aggression, indicating that it was more often bidirectional rather than
      unidirectional. In addition, aggressors clearly defended each other when they
      shared their targets of aggression, whereas a marginally significant trend
      appeared for defending between victims who were victimized by the same
      aggressors. Furthermore, teacher-rated dominance was positively associated with
      children's involvement in both aggression and victimization, and teacher-rated
      insecurity was associated with less aggression, but not with victimization. These
      findings suggest that those who are reported as being victimized may retaliate,
      or be aggressive themselves, and do not display some of the vulnerabilities
      reported among older groups of victims. The findings are in line with the
      proposition that young aggressors are less strategic than older children in
      targeting vulnerable victims. The network approach to peer victimization and
      defending contributes to understanding the social processes facilitating the
      development of aggression in early childhood.

PMID- 29577330
TI  - Technical Note: Impact of region of interest size and location in Gafchromic film
      dosimetry.
AB  - PURPOSE: To evaluate dependence of measured dose on size and location of region
      of interest (ROI) in Gafchromic EBT3 film dosimetry. METHODS: Gafchromic EBT3
      films were irradiated perpendicularly using the 6MV beam from a linear
      accelerator at 10 cm depth (100 cm SSD) of a 30 * 30 * 20 cm3 solid water phantom
      for a range of field sizes of 6 * 6 to 100 * 100 mm2 . ImageJ software was used
      for reading pieces of film. The appropriate location of ROIs in scanned films was
      found by two methods. First, the ROI was visually placed at the center of image.
      Second, the profile of pixel value versus distance was plotted and the center of
      profile was used for drawing ROI. Each scanned film was read using both methods
      and for three ROI sizes (1, 2, and 4 mm). A plastic scintillator, Exradin W1, was
      used as the reference dosimeter. RESULTS: Comparing the three ROI sizes using
      both methods showed that there was less than 2% difference from reference in
      output factor measurements for field sizes larger or equal to 10 * 10 mm2 . The
      percentage differences were increased in field sizes smaller than 10 * 10 mm2 and
      for ROI size of 4 * 4 mm2 for both centered-ROI and profiled-ROI methods. The
      mean percentage differences from reference measurements, for field sizes of 100 *
      100 to 20 * 20 mm2 , were smaller than 1% in both methods of ROI positioning. For
      field sizes of 15 * 15 and 10 * 10 mm2 , the smaller mean percentage differences
      were observed in profiled-ROI (4 * 4 mm2 ) and centered-ROI (4 * 4 mm2 ). For the
      field sizes of 8 * 8 and 6 * 6 mm2 , the profiled-ROI (2 * 2 mm2 ) had smallest
      mean percentage difference, which was 0.88%. CONCLUSION: The ROI size of 4 * 4
      mm2 is appropriate for dose measurements in field sizes of 100 * 100 mm2 to 10 *
      10 mm2 , regardless of the method of finding location of ROI. In field sizes
      smaller than 10 * 10 mm2 , finding location of the ROI by profile of pixel values
      increases the accuracy of measurement, and ROI size of 2 * 2 mm2 has the smallest
      difference from the reference dose measurements.

PMID- 29577331
TI  - Rapid and flexible creativity in musical improvisation: review and a model.
AB  - Creativity has been defined as the ability to produce output that is novel,
      useful, beneficial, and desired by an audience. But what is musical creativity,
      and relatedly, to what extent does creativity depend on domain-general or domain
      specific neural and cognitive processes? To what extent can musical creativity be
      taught? To answer these questions from a reductionist scientific approach, we
      must attempt to isolate the creative process as it pertains to music. Recent work
      in the neuroscience of creativity has turned to musical improvisation as a window
      into real-time musical creative process in the brain. Here, I provide an overview
      of recent research in the neuroscience of musical improvisation, especially
      focusing on multimodal neuroimaging studies. This research informs a model of
      creativity as a combination of generative and reactive processes that coordinate
      their functions to give rise to perpetually novel and aesthetically rewarding
      improvised musical output.

PMID- 29577332
TI  - Human placental PPAR-gamma and SOX-2 expression in serologically proved
      toxoplasmosis.
AB  - To explore PPAR-gamma and SOX-2 transcription factors expression in placenta
      according to maternal anti-Toxoplasma gondii serological profile during pregnancy
      and pregnancy outcome. The study included 240 placentas, grouped according to IgM
      and IgG serostatus and then subgrouped according to pregnancy outcome that varied
      between miscarriages, premature labour, stillbirth and giving birth to CNS
      anomaly or apparently healthy neonates. Samples were H&E stained and
      histopathologically scored blindly. PPAR-gamma expression was measured by ELISA,
      while SOX-2-positive nuclei were stained immunohistochemically to be calculated
      by ImageJ. The mean pathological score was significantly higher in IgM+ve and IgG
      rising than IgG-ve and persistent low groups. Former groups showed significantly
      higher PPAR-gamma (mean = 258.63, 227.11). However, PPAR-gamma was higher in
      apparently healthy neonate subgroups. SOX-2 was significantly lower in IgM+ve and
      IgG rising groups (mean = 12.87, 43.13) and associated with obvious fibrosis. SOX
      2 lowest count was in CNS anomaly subgroup. PPAR-gamma and SOX-2 changes may give
      clues of how Toxoplasma induces pathogenesis during vertical transmission.
      Triggering PPAR-gamma expression may be a tool to downregulate the inflammatory
      response and establish a metabolically permissive cellular environment for
      Toxoplasma persistence. Low SOX-2 is suspected to disturb placental mesenchymal
      stem cells pluripotency and neuroectoderm development.

PMID- 29577333
TI  - NP30 stimulates Th17 differentiation through DC in Schistosomiasis Japonicum.
AB  - The murine monoclonal anti-idiotypic antibody, NP30, is a potential vaccine
      candidate against Schistosoma japonicum. Previous studies have revealed that NP30
      has an immunoregulatory effect, but the underlying mechanism for this effect
      remains unknown. This study shows that NP30 induces dendritic cell (DC)
      maturation and increases the production of pro-inflammatory cytokines. The
      expression of CD86 and MHC II was upregulated in DCs following stimulation with
      NP30 in vitro. Moreover, NP30 induced Th17 polarization by increasing the
      production of IL-6 and TGF-beta. In vivo, Th17 differentiation was induced by the
      production of key pro-inflammatory cytokines, including IL-6and TGF-beta, from
      DCs of NP30-immunized mice. These results indicate that NP30 promotes Th17
      polarization through DC activation, preventing serious schistosomiasis.

PMID- 29577334
TI  - Ecological Networks and Community Attachment and Support Among Recently Resettled
      Refugees.
AB  - Interventions aimed at enhancing mental health are increasingly centered around
      promoting community attachment and support. However, few have examined and tested
      the specific ecological factors that give rise to these key community processes.
      Drawing from insights from the ecological network perspective, we tested whether
      spatial and social overlap in routine activity settings (e.g., work, school,
      childcare) with fellow ethnic community members is associated with individuals'
      attachment to their ethnic communities and access to social resources embedded in
      their communities. Data on routine activity locations drawn from the Refugee Well
      Being Project (based in a city in the Southwestern United States) were used to
      reconstruct the ecological networks of recently resettled refugee communities,
      which were two-mode networks that comprise individuals and their routine activity
      locations. Results indicated that respondents' community attachment and support
      increased with their ecological network extensity-which taps the extent to which
      respondents share routine activity locations with other community members. Our
      study highlights a key ecological process that potentially enhances individuals'
      ethnic community attachment that extends beyond residential neighborhoods.

PMID- 29577336
TI  - Delayed-type allergy to cobalt-comparison of a flow cytometric lymphocyte
      proliferation test with patch testing.
AB  - BACKGROUND: The patch test is the standard procedure for diagnosing delayed-type
      sensitization. If a patch test is not possible, the flow cytometric lymphocyte
      proliferation test (LPT), which determines the number and type of cells
      responding to a specific antigen in vitro, might be considered as an alternative.
      OBJECTIVES: Our aim was to establish a flow cytometric LPT for the detection of
      delayed-type allergic responses to cobalt, and to determine the correlation
      between stimulation indices (SIs) in LPT and the grade of patch test reactions.
      With the patch test as a diagnostic reference, we also assessed the sensitivity
      and specificity of the LPT. METHODS: Fifty-four patients patch tested with the
      baseline series including cobalt (CoCl2 ) were additionally tested with the flow
      cytometric LPT with CoCl2 . RESULTS: There was a significant correlation between
      the results of both tests: rs  = 0.43; P = .001. The LPT with CoCl2 showed a
      sensitivity of 52.6% and a specificity of 85.7%. Corresponding to the low
      sensitivity of the LPT, high likelihood ratios for a positive patch test reaction
      were reached only in cases of strong lymphocyte proliferation (SI >= 10).
      CONCLUSIONS: In cases of clearly increased SIs, the flow cytometric LPT with
      CoCl2 gives relevant diagnostic information, and represents a valuable
      alternative to patch testing.

PMID- 29577335
TI  - Evaluation of postharvest calcium treatment and biopreservation with
      Lactobacillus rhamnosus GG on the quality of fresh-cut 'Conference' pears.
AB  - BACKGROUND: Biological preservation with probiotic bacteria has arisen as an
      alternative to control the growth of foodborne pathogens on food. The objective
      of this work was to evaluate the effect of postharvest calcium application and
      biopreservation with Lactobacillus rhamnosus GG on the quality and
      bioaccessibility of total phenolic content and antioxidant activity in fresh-cut
      pears. RESULTS: The immersion of whole pears in a calcium chloride solution did
      not provide added value. Despite the increase in observed activity of PME and PPO
      enzymes in fresh-cut pears during storage, the browning index and firmness values
      were constant for all samples. The antioxidant properties, including antioxidant
      activity, total phenolic content and vitamin C content, were maintained during
      storage, but a significant decrease was observed after in vitro simulated
      digestion. Ca/LGG samples showed the lowest calcium content (1.75 +/- 0.00 g kg-1
      ) after 9 d of storage at 4  degrees C. In general, the overall visual quality
      scores were higher in fresh-cut pears treated with L. rhamnosus GG than in non
      treated pears, with the highest values in the NoCa/LGG (7.7 +/- 0.2) samples
      after 9 d at 4  degrees C. CONCLUSION: Fresh-cut pears with a postharvest
      treatment of calcium and immersed in a solution containing antioxidant agents and
      probiotic bacteria could be a suitable alternative to dairy products for
      maintaining the overall quality of fruit for up to 9 d of storage. (c) 2018
      Society of Chemical Industry.

PMID- 29577337
TI  - A high DQE water-equivalent EPID employing an array of plastic-scintillating
      fibers for simultaneous imaging and dosimetry in radiotherapy.
AB  - PURPOSE: First measurements of the imaging performance of a novel prototype water
      equivalent electronic portal imaging device (EPID) designed for simultaneous
      imaging and dose verification in radiotherapy and previously characterized by our
      group for dosimetry are reported. Experiments were conducted to characterize the
      prototype's imaging performance relative to a standard commercial EPID and Monte
      Carlo (MC) simulations were performed to quantify the impact of several detector
      parameters on image quality and to inform the design of a proposed next
      generation prototype. METHODS: The prototype EPID utilizes an array of 3 cm long
      plastic-scintillating fibers in place of the metal plate/phosphor screen in
      standard EPIDs. Using a clinical 6 MV photon beam, the prototype's modulation
      transfer function (MTF), noise power spectrum (NPS), and detective quantum
      efficiency (DQE) were measured and compared to measurements taken using a
      standard commercial EPID. A sensitivity analysis was then performed using the MC
      model by quantifying these metrics while varying the values of several
      geometrical and optical transport parameters that were unspecified by the
      prototype manufacturer. Finally, the MC model was used to quantify the imaging
      performance of a proposed next-generation prototype incorporating 1.5 cm long
      fibers that is better suited for integration with clinical portal imaging and
      dosimetry systems. RESULTS: The prototype EPID's zero spatial frequency DQE
      exceeded 3%, more than doubling that measured with the standard EPID (1.25%).
      This increased DQE was a consequence of using a prototype array detector with a
      greater equivalent thickness than the combined copper plate and phosphor screen
      in a standard EPID. The increased thickness of our prototype decreased spatial
      resolution relative to the standard EPID; however, the prototype EPID NPS was
      also lower than that measured with the standard EPID across all spatial
      frequencies. The sensitivity analysis demonstrated that the NPS was strongly
      affected by the roughness of the boundaries between fiber core and cladding
      regions. By comparison, the MTF was most sensitive to beam divergence and the
      presence of air between the fiber array and underlying photodiode panel.
      Simulations demonstrated that by optimizing these parameters, DQE(0) >4% may be
      achievable with the proposed next-generation prototype design. CONCLUSIONS: The
      first measurements characterizing the imaging performance of a novel water
      equivalent EPID for imaging and dosimetry in radiotherapy demonstrated a DQE(0)
      more than double that of a standard EPID. MC simulations further demonstrated the
      potential for developing a next-generation prototype better suited for clinical
      translation with even higher DQE.

PMID- 29577339
TI  - Frailty as a predictor of negative outcomes after cardiac resynchronization
      therapy.
AB  - AIM: To assess the prevalence of frailty among patients who had cardiac
      resynchronization as well as the influence of frailty on the main endpoints
      during follow-up. METHODS: The study included 156 patients (aged 74.33 +/- 6.75;
      27 W) with diagnosed heart failure who were hospitalized for the implantation of
      a cardiac resynchronization device. The Tilburg Frailty Indicator questionnaire
      was used to evaluate frailty syndrome. RESULTS: Frailty syndrome was diagnosed in
      75.64% of patients who were included. The average value of frailty for the whole
      group was 6.21 +/- 1.94, for the physical domain 4.29 +/- 1.32, for the
      psychological domain 1.40 +/- 1.04, and for the social domain 0.51 +/- 0.57.
      During the follow-up period, 5.7% of the patients died, and the mortality rate
      was not statistically higher (P  =  0.5795) among patients who were diagnosed
      with frailty syndrome (6.78%) compared to robust patients (2.63%). Analysis of
      the complications and first electrical storm episodes demonstrated that these
      events did not occur in patients with no identifiable frailty syndrome. These
      occurred at a rate of 4.24% (complications) and 2.54% (electric storm) in
      patients with frailty syndrome. CONCLUSIONS: Frailty syndrome can be an important
      predictor of negative outcomes in patients with heart failure who undergo cardiac
      resynchronizations.

PMID- 29577338
TI  - Technical Note: Single time point dose estimate for exponential clearance.
AB  - OBJECTIVE: Although personalized dosimetry may be desirable for radionuclide
      therapy treatments, the multiple time samples required to determine the total
      integrated activity puts a burden on patients and clinic resources. The aim of
      this paper is to demonstrate that when some prior knowledge is known about the
      tracer kinetic parameters, the total integrated activity (and thus radiation
      dose) can be estimated from a single time sample. METHODS: Mathematical
      derivations have been performed to generate equations for the total integrated
      activity in terms of a single time sample of activity for monoexponential and
      biexponential clearance. Simulations were performed using both exponential models
      where the rate constants and associated parameters were randomly sampled from
      distributions with a known mean. The actual total integrated activity for each
      random sample was compared with the estimated total integrated activity using the
      mean value of the parameters. Retrospective analysis of 90 Y DOTATOC data from a
      clinical trial provided a comparison of actual kidney dose with the estimated
      kidney dose using the single time point approach. RESULTS: The optimal sampling
      time for the single point approach was found to be equal to the mean time of the
      rate constant. The simulation results for the monoexponential and biexpoential
      models were similar. Regressions comparing the actual and estimated total
      integrated activity had very high correlations (r2  > 0.95) along with acceptable
      standard errors of estimate, especially at the optimal sampling point. The
      retrospective analysis of the 90 Y DOTATOC data also yielded similar results with
      an r2  = 0.95 and a standard error of estimate of 61 cGy. CONCLUSIONS: In
      situations where there is prior knowledge about the population averages of
      kinetic parameters, these results suggest that the single time point approach can
      be used to estimate the total integrated activity and dose with sufficient
      accuracy to manage radionuclide therapy. This will make personalized dosimetry
      much easier to perform and more available to the community.

PMID- 29577340
TI  - Safety and efficacy of apixaban versus warfarin in patients with end-stage renal
      disease: Meta-analysis.
AB  - BACKGROUND: At the present, apixaban is the only nonvitamin K oral anticoagulant
      approved by the Food and Drug Administration for use with patients with
      creatinine clearance <15 mL/min or end-stage renal disease (ESRD). However, the
      recommendations are based on pharmacokinetic and pharmacodynamic data and there
      was lack of clinical trial evidence. We aimed to assess safety and efficacy of
      apixaban in patients with advanced chronic kidney disease (CKD) or ESRD. METHODS:
      Databases were searched through November 2017. Studies that reported incidence or
      odd ratios of bleeding complications or thromboembolic events in the use of
      apixaban in patients with CKD stage 4-5 or ESRD on dialysis were included. Effect
      estimates from the individual study were extracted and combined using random
      effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five
      studies were included into the analysis consisting of 43,850 patients in
      observational cohort studies. The majority of patients (87%) used apixaban for
      atrial fibrillation. The pooled estimated incidence of any bleeding complications
      on apixaban was 17.4% (95% confidence interval [CI]: 13.0%-23.0%). Compared to
      warfarin, apixaban was significantly associated with reduced risk of major
      bleeding (pooled odds ratio [OR], 0.42; 95% CI, 0.28-0.61). In studies in ESRD
      patients on dialysis, the pooled OR of major bleeding was 0.27 (95% CI, 0.07
      0.95). There was no significant difference in risk of thromboembolic events in
      advanced CKD or ESRD patients on apixaban versus vitamin K antagonists (pooled
      OR, 0.56; 95% CI, 0.23-1.39). CONCLUSIONS: Among patients with advanced CKD and
      ESRD, the use of apixaban was associated with lower risk of major bleeding
      compared to warfarin, and was found to be relatively effective with no excess
      risk of thromboembolic events.

PMID- 29577341
TI  - Impact of intraoperative mechanical ventilation on left ventricular lead function
      in cardiac resynchronization therapy.
AB  - BACKGROUND: Intraoperative controlled mechanical ventilation (CMV) changes the
      intrathoracic geometry and may impact postoperative left ventricular (LV) lead
      function after CRT implantation. This multicenter study investigates the effect
      of intraoperative ventilation setting (spontaneous breathing [SB] vs CMV) on
      postoperative LV lead function taking into account patients' body mass index
      (BMI). METHODS: CRT implantation was performed at two centers during SB in 92 and
      during CMV in 73 patients. Follow-up was carried out after 3 +/- 5 and 36 +/- 53
      days. Functional lead parameters (FLP; pacing threshold and impedance),
      postoperative adverse events (A;  phrenic nerve stimulation [PNS] and lead
      malfunction), and patients' BMI were assessed. Delta values of FLP between
      baseline and follow-up visits were analyzed applying an analysis of covariance
      model to detect subclinical alterations in LV lead function. RESULTS: AE occurred
      in a total of 36 (21%) patients. PNS was observed in 26 (15%) patients and LV
      lead repositioning due to malfunction was necessary in 10 (6%) patients. Both AE
      and FLP delta values between baseline and follow-up were not associated with
      intraoperative ventilation settings nor the patients' BMI. CONCLUSIONS: This
      study demonstrates that there is no impact of the intraoperative ventilation
      setting (SB vs CMV) on postoperative FLP or the occurrence of AE. This is also
      the case taking into account the BMI. With respect to these findings both
      approaches-sedation only or general anaesthesia including CMV-can be safely
      implemented during CRT implantation.

PMID- 29577342
TI  - System justification enhances well-being: A longitudinal analysis of the
      palliative function of system justification in 18 countries.
AB  - According to the palliative function of ideology hypothesis proposed by System
      Justification Theory, endorsing system-justifying beliefs is positively related
      to general psychological well-being, because this fulfils existential, epistemic,
      and relational needs. We discuss and address three main issues: (1) the role of
      societal inequality, (2) comparisons by social status, and (3) cross-sectional
      versus longitudinal research. We used a longitudinal survey of representative
      online samples (N = 5,901) from 18 countries. The results supported the main
      argument proposed by the theory, in that system justification was positively and
      significantly related to life satisfaction and negatively related to anxiety and
      depression. The pattern of results suggested that the palliative function of
      system justification is more homogeneously distributed across individual and
      collective measures of social status than proposed by the theory, because the
      function was unaffected either by society-level inequality or by individual-level
      social status. These results allow us to infer that one of the reasons for the
      high stability of social arrangements is located in the psychological domain of
      palliative effects.

PMID- 29577343
TI  - Perceptions of Housing and Shelter among People with Histories of Unstable
      Housing in three Cities in Canada: A Qualitative Study.
AB  - Housing is a key social determinant of health that contributes to the well
      documented relationship between socioeconomic status and health. This study
      explored how individuals with histories of unstable and precarious housing
      perceive their housing or shelter situations, and the impact of these settings on
      their health and well-being. Participants were recruited from the Health and
      Housing in Transition study (HHiT), a longitudinal, multi-city study that tracked
      the health and housing status of people with unstable housing histories over a 5
      year period. For the current study, one-time semi-structured interviews were
      conducted with a subset of HHiT study participants (n = 64), living in three
      cities across Canada: Ottawa, Toronto, and Vancouver. The findings from an
      analysis of the interview transcripts suggested that for many individuals changes
      in housing status are not associated with significant changes in health due to
      the poor quality and precarious nature of the housing that was obtained. Whether
      housed or living in shelters, participants continued to face barriers of poverty,
      social marginalization, inadequate and unaffordable housing, violence, and lack
      of access to services to meet their personal needs.

PMID- 29577344
TI  - This corrosion: A systematic review of the association between alternative
      subcultures and the risk of self-harm and suicide.
AB  - BACKGROUND: Rates of self-harm and suicide are increasing in young people. The
      literature suggests that individuals who identify with alternative subcultures
      (e.g., Goth) may be at a greater risk. OBJECTIVE: To explore the prevalence of
      self-harm and suicide in alternative subcultures and the factors that might
      contribute to this increased risk. METHOD: Using a systematic strategy, the
      databases PsycINFO, Scopus, MEDLINE and Web of Science, and the E-Thesis online
      service (ETHOS) were searched for English language only papers, with no
      restrictions in terms of date of publication. Papers were selected that included
      data on the relationship between either alternative subculture identity (e.g.,
      Goth) or preference for alternative music (e.g., Heavy Metal) and self-harm or
      suicide. Ten quantitative papers were included: seven cross-sectional, two
      longitudinal and one cross-sectional state-level comparison study. Two
      qualitative papers were also included. Studies were assessed by two reviewers for
      risk of bias. RESULTS: The findings indicated that individuals who associated
      with alternative subcultures were at a greater risk of self-harm and suicide.
      Whilst qualitative papers identified potential mechanisms (e.g., exposure to self
      harm and the way self-harm is presented or normalized), there remains limited
      support for these mechanisms. CONCLUSIONS: More research is required to
      understand the association between self-harm, suicide and alternative subculture
      affiliation, and the factors underlying it. Longitudinal studies and studies
      focusing on mechanism are particularly important. PRACTITIONER POINTS: The review
      supports the suggestion that those who identify as belonging to an alternative
      subculture may be at a higher risk of self-harm and suicidal behaviour. It also
      presents preliminary evidence that alternative affiliation predicts self-harm
      over time, and that this effect holds whilst adjusting for a number of likely
      confounders. The findings highlight the importance of increasing the awareness of
      the victimization and potential risk that these groups hold and suggests areas
      for intervention in health, educational, and social services. The review does
      not, however, indicate specifically what it is about alternative subculture
      affiliation (or alternative music preference) that could contribute to the risk
      of self-harm. Consequently, studies with a greater focus on mechanisms are
      needed. Methodological limitations (e.g., cross-sectional studies, small sample
      of 'alternative' participants, westernized samples) restricted the reliability
      and validity of the results which impacted on the extent to which the findings
      could be generalized more widely.

PMID- 29577345
TI  - Microtissue engineering root canal dentine with crosslinked biopolymeric
      nanoparticles for mechanical stabilization.
AB  - AIM: To evaluate the functional strain distribution pattern in root dentine
      following canal preparation and root canal surface engineering with crosslinked
      biopolymeric nanoparticles using digital moire interferometry (DMI). METHODOLOGY:
      Root dentine specimens were prepared, grating material replicated and tested for
      10-50 N, compressive loads in a customized high-resolution, whole-field moire
      interferometry set-up. Digital moire fringes were acquired to determine the
      strain distribution pattern at specific regions of interest before and after
      canal enlargement, and dentine surface engineering with a chitosan nanoparticle
      crosslinker solution. Fringe patterns were acquired, and strain distribution
      pattern in the direction perpendicular to dentinal tubules (U-field) and parallel
      to dentinal tubules (V-field) was analysed with custom digital image-processing
      software. Data were analysed with a statistical method on trend analysis at 0.05
      significant level. RESULTS: Distinct deformation patterns perpendicular to the
      dentinal tubules were observed in root dentine. Root canal dentine removal
      following instrumentation resulted in an increase in strain distribution, which
      increased with an increase in applied loads (P < 0.01). The root canal dentine
      engineered with crosslinked nanoparticles demonstrated a conspicuous decrease in
      previously increased strain distribution in both coronal and apical root dentine
      (P < 0.01). A significant increase in tensile strain in root dentine was observed
      subsequent to instrumentation in the direction parallel to dentinal tubules (P <
      0.01). There was a significant reduction in the tensile strain formed at the
      apical region of the instrumented root dentine following crosslinked nanoparticle
      treatment (P < 0.05). CONCLUSIONS: This study highlighted the potential of root
      canal dentine microtissue engineering with crosslinked chitosan nanoparticle to
      improve radicular strain distribution patterns in instrumented canals.

PMID- 29577346
TI  - The impact of right ventricular function assessed by 2-dimensional speckle
      tracking echocardiography on early mortality in patients with inferior myocardial
      infarction.
AB  - BACKGROUND: Right ventricular (RV) involvement in inferior myocardial infarction
      (MI) increases in-hospital morbidity and mortality. HYPOTHESIS: RV systolic
      dysfunction assessed by 2-dimensional speckle tracking echocardiography (STE)
      might be a predictor of early mortality in patients with acute inferior MI.
      METHODS: Eighty-one consecutive patients with acute inferior MI (mean age, 60.8
      +/- 12.7 years; 18 females) were included. RV myocardial involvement was defined
      as an elevation >1 mm in V1 or V4 R within 12 hours of symptom onset. RV function
      was assessed by STE. Patients were followed for 30 days for all-cause mortality.
      RESULTS: Thirty-eight patients had RV myocardial involvement, and they had
      significantly lower tricuspid annular plane systolic excursion (TAPSE), tricuspid
      annular systolic velocity (RVS), and left ventricular (LV) and RV global
      longitudinal strain (GLS). Nine patients (11%) died within 30 days. The mean age
      of mortality group was higher with more female frequency. They had significantly
      higher pro-BNP, hs-troponin T, and creatinine levels, but lower hemoglobin
      levels. TIMI 3 flow was significantly less achieved in mortality group. RV
      myocardial involvement was more frequent in the mortality group, and they had
      significantly lower TAPSE, RVS, and LV and RV GLS. Multivariate analysis revealed
      that age and RV GLS were independent predictors of early mortality. RV GLS <= 
      14% predicted early mortality in patients with acute inferior MI with a
      sensitivity of 88.9% and a specificity of 62.5% (AUC: 0.817, P = 0.002).
      CONCLUSIONS: RV GLS may be useful in predicting early mortality in patients with
      acute inferior MI.

PMID- 29577348
TI  - Preoperative autologous blood collection before bone marrow harvests in
      haploidentical related donors: is it justified?
AB  - BACKGROUND: With the increasing safety of allogeneic blood supply and declining
      need for transfusion due to patient blood management, the practice of
      preoperative autologous donation (PAD) continues to decline. The practice gained
      popularity during the 1980s and 1990s with the emergence of transfusion
      transmitted human immunodeficiency virus and hepatitis C. At the peak of this
      public concern, the National Marrow Donor Program recommended that marrow donors
      have 1 to 3 autologous units of blood collected before their marrow harvest to
      minimize the likelihood of allogeneic transfusion. After three decades, the
      practice remains prevalent in marrow donors. We aimed to study the efficacy of
      PAD in healthy marrow donors. STUDY DESIGN AND METHODS: PADs performed before
      marrow harvest in healthy donors at our center between January 2013 and July 2015
      were reviewed. The utilization of autologous units and decrease in hemoglobin
      levels due to PAD and marrow harvest were studied. Similar practices were
      assessed in the rest of the United States through a brief survey. RESULTS: Of a
      total of 262 autologous units collected from 136 donors, 25.2% were wasted.
      Ninety-nine percent of the marrow donors received at least 1 unit of blood
      irrespective of the need. PAD contributed to preoperative anemia, exposing three
      donors to allogeneic blood transfusion. The survey results showed a mixed
      response with some institutions continuing and others not practicing PAD.
      CONCLUSION: PADs are not justified in healthy marrow donors as they expose them
      to a risk of preoperative anemia and hence a greater risk of transfusion.

PMID- 29577347
TI  - Electrocardiographic predictors of validated right ventricular outflow tract
      septal pacing for correct localization of transthoracic echocardiography.
AB  - BACKGROUND: Electrocardiographic (ECG) characteristics of true right ventricular
      outflow tract (RVOT) septal pacing have not been clearly demonstrated.
      HYPOTHESIS: We hypothesized that ECG parameters would help operators
      differentiate true RVOT septum from non-septal septum. METHODS: We analyzed 151
      patients who underwent pacemaker implantation with a ventricular lead in the
      RVOT. Transthoracic echocardiographic (TTE) determination of pacing sites was
      applied in all patients after implantation. A 12-lead ECG was recorded during
      forced ventricular pacing. RESULTS: According to TTE orientation, pacing at the
      RVOT septum was achieved in 94 patients (62.3%). Compared with nonseptal pacing,
      septal pacing had significantly shorter QRS duration (139.2 +/- 18.5 ms vs 155.5
      +/- 14.7 ms; P < 0.001). More frequent negative or isoelectric QRS vector in lead
      I (76% vs 32%; P < 0.001), lead II/III R-wave amplitude ratio < 1 (52% vs 25%; P
      = 0.001), and aVR/aVL QS-wave amplitude ratio < 1 (59% vs 32%; P = 0.001) were
      observed in septal pacing. Transitional zone (TZ) score (3.8 +/- 0.96 vs 4.2 +/-
      0.90; P = 0.004) and TZ index (0.3 +/- 0.5 vs 0.6 +/- 0.7; P = 0.008) were
      significantly lower in septal pacing than in nonseptal pacing, respectively. In
      multivariate analysis, paced QRS duration and negative or isoelectric QRS vector
      in lead I independently predicted RVOT septal pacing (P < 0.001). At ROC curve
      analysis, paced QRS duration <=145 ms identified RVOT septal pacing with 85.1%
      sensitivity and 78.9% specificity. CONCLUSIONS: This study reveals the
      heterogeneity of lead placement within the RVOT. Narrower paced QRS duration and
      negative or isoelectric QRS vector in lead I independently predict RVOT septal
      pacing.

PMID- 29577349
TI  - Natural history and clinical detection of undiagnosed coeliac disease in a North
      American community.
AB  - BACKGROUND: Coeliac disease is a substantially underdiagnosed disorder, with
      clinical testing currently guided by case finding. AIM: To determine the presence
      of indications for diagnostic testing and frequency of clinical testing in
      undiagnosed coeliac disease. METHODS: This was a case-control study of adults
      without prior diagnosis of coeliac disease. Undiagnosed cases were identified
      through sequential serology, and unaffected age- and gender-matched controls were
      selected. Medical records were systematically reviewed for indications for and
      evidence of clinical testing. RESULTS: Of 47 557 adults, 408 cases of undiagnosed
      coeliac disease were identified. 408 serology negative matched controls were
      selected. Eight-matched pairs were excluded, leading to 800 included individuals
      (61% female; median age 44.2 years). The odds of any indication for clinical
      testing were similar among undiagnosed coeliac disease and controls (odds ratio
      (OR) 1.18; 95% CI: 0.85-1.63, P = 0.32). Most individual indications were not
      associated with serologic status. Exceptions to this include hypothyroidism,
      which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and
      chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease
      were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P
      = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune
      diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P
      = 0.001). CONCLUSION: This study strongly suggests that current case finding is
      not effective in detecting undiagnosed coeliac disease. Individuals with
      undiagnosed coeliac disease were more likely than controls to develop indications
      for testing overtime. A more effective method for detection of coeliac disease is
      needed.

PMID- 29577350
TI  - Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg
      negative Caucasian patients in the Grey Zone.
AB  - BACKGROUND: Grey Zone (GZ) is an ill-defined situation including patients falling
      between inactive carrier (IC) state and HBeAg-negative chronic hepatitis B (HBeAg
      negative CHB). AIMS: To assess the long-term outcomes of GZ patients compared to
      IC in the absence of treatment. METHODS: Retrospective analysis of 287 IC and GZ
      HBeAg-negative patients. Patients were classified into 4 groups at baseline: HBV
      DNA <2000 IU/mL and ALT <40 U/L (IC), HBV-DNA <2000 IU/mL and ALT 40-80 U/L (GZ
      1), HBV-DNA 2000-20 000 IU/mL and ALT <40 U/L (GZ-2) or ALT 40-80 U/L (GZ-3).
      Data were also analysed using AASLD ALT criteria. RESULTS: After a median follow
      up of 8.2 (5-19) years, HBsAg loss occurred in about 15% ICs or GZ patients.
      Transition into IC state occurred in 40% of GZ patients. DNA fluctuations >2000
      IU/mL correlated inversely with transition into IC and HBsAg loss. HBsAg levels
      were significantly lower in ICs than in GZ patients (338 IU/mL [20-3269] vs 5763
      IU/mL [2172-17 754]; P < 0.05). Among the latter group, there was an increasing
      gradient of HBsAg levels from GZ-1 to GZ-3 patients (P < 0.05). HBeAg-negative
      CHB occurred in only 18 (6.3%) GZ patients. No patient developed cirrhosis nor
      advanced fibrosis. ALT/HBV-DNA fluctuations and HBeAg-negative CHB development
      were more frequent in genotype B/C patients, whereas HBsAg loss occurred only in
      genotype A/D patients. CONCLUSIONS: Most Caucasian GZ patients present excellent
      long-term outcomes in the absence of treatment, with a high rate of HBsAg loss
      and low rate of progression to HBeAg-negative CHB. HBV-genotyping and HBsAg
      levels could help to predict outcomes and better classify GZ patients.

PMID- 29577352
TI  - Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit
      fetuses.
AB  - INTRODUCTION: Lung hypoplasia and pulmonary arterial hypertension in congenital
      diaphragmatic hernia lead to a high perinatal mortality. Although sustained
      fetoscopic tracheal occlusion (TO) improves lung development, a major side effect
      is abnormal pneumocyte differentiation. This study evaluated the potential
      ability of intratracheal retinoic acid (RA) administration to reduce adverse
      effects of sustained TO in a rabbit model of diaphragmatic hernia. METHODS: A
      left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits.
      On day 28, the same rabbits underwent sham surgery or TO, with an injection of
      empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the
      lungs were processed for histology, immunohistochemistry, and gene expression
      quantification. RESULTS: A tracheal RA injection at the time of TO had no effect
      on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue
      composition. Retinoic acid plus TO had synergic effects on vascular measurements,
      proportional medial thickness, and endothelin-1 receptor type-A gene expression.
      The most noticeable effect was recovery of normal pneumocyte differentiation.
      CONCLUSION: Retinoic acid plus TO prevented abnormal pneumocyte differentiation
      and seemed to have a beneficial effect on pulmonary vascularization.

PMID- 29577351
TI  - A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?:
      Brain tumors and microcephaly arise from opposing derangements regulating
      progenitor growth. Drivers of microcephaly could be attractive brain tumor
      targets.
AB  - New targets for brain tumor therapies may be identified by mutations that cause
      hereditary microcephaly. Brain growth depends on the repeated proliferation of
      stem and progenitor cells. Microcephaly syndromes result from mutations that
      specifically impair the ability of brain progenitor or stem cells to proliferate,
      by inducing either premature differentiation or apoptosis. Brain tumors that
      derive from brain progenitor or stem cells may share many of the specific
      requirements of their cells of origin. These tumors may therefore be susceptible
      to disruptions of the protein products of genes that are mutated in microcephaly.
      The potential for the products of microcephaly genes to be therapeutic targets in
      brain tumors are highlighted hereby reviewing research on EG5, KIF14, ASPM, CDK6,
      and ATR. Treatments that disrupt these proteins may open new avenues for brain
      tumor therapy that have increased efficacy and decreased toxicity.

PMID- 29577353
TI  - Determination of topiramate by capillary electrophoresis with capacitively
      coupled contactless conductivity detection: A powerful tool for therapeutic
      monitoring in epileptic patients.
AB  - Topiramate (TPM) is the main antiepileptic drug used for the control of partial
      and generalized seizures in both adults and children. In association with
      clinical observations, the analysis of plasmatic concentration of TPM is of
      utmost importance for the individual adjustment of the administered dose to the
      patient. In the present work, a bioanalytical method was developed and validated
      for TPM analysis in plasma samples by capillary electrophoresis with capacitively
      coupled contactless conductivity detection (CE-C4 D). A simple background
      electrolyte composed of 15 mmol/L triethylamine, hydrodynamic injections (0.8 psi
      for 5 s) and a moderate separation voltage (20 kV) were used, rendering
      relatively short analysis times (<3 min). The sample pre-treatment was carried
      out by liquid-liquid extraction using methyl terc-butyl ether as solvent and 200
      MUL of plasma. The method was validated according to the official guidelines from
      the European Medicine Agency and showed linearity in plasmatic concentration
      range from 1 to 30 MUg/mL, which covers the clinically-relevant interval. The
      lower limit of quantification of 1 MUg/mL obtained also allows following patients
      with low dosage of the drug. The method was successfully applied to analysis of
      plasma samples and allowed the identification of 80% under-medicated patients in
      the analyzed patient pool.

PMID- 29577354
TI  - Sexual Portrait of Couples Seeking Relationship Therapy.
AB  - This study sought to provide information about the sexual well-being of 298 mixed
      sex couples seeking relationship therapy and determined the extent to which
      problems with sexual functioning and dyadic adjustment of both partners are
      associated with sexual satisfaction. Partners completed measures of dyadic
      adjustment, sexual satisfaction, and sexual functioning. Thirty percent of
      couples reported a clinically significant sexual problem. Compared to their male
      partners, the women were more likely to report a sexual problem as well as lower
      dyadic adjustment, sexual satisfaction, and overall sexual functioning. Path
      analysis indicated that relationship adjustment uniquely predicted individuals'
      own sexual satisfaction; problems in sexual functioning uniquely predicted own
      and partner sexual satisfaction. Findings underscore the need to address sexual
      problems in relationship therapy.

PMID- 29577355
TI  - Simultaneous determination of zidebactam and cefepime in dog plasma by LC-MS/MS
      and its application to pre-clinical pharmacokinetic study.
AB  - A precise and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS)
      bioanalytical method has been developed and validated for the simultaneous
      quantification of zidebactam (ZID) and cefepime (FEP) in dog plasma. Ceftazidime
      was used as an internal standard. Protein precipitation method was used as sample
      preparation approach. The calibration curve obtained was linear (r >= 0.99) over
      the concentration range 0.156-80 MUg/mL for ZID and 0.312-160 MUg/mL for FEP. The
      method was validated as per US Food and Drug Administration guidelines and the
      results met the acceptance criteria. A run time of 3.5 min for each sample made
      it possible to analyze the maximum number of samples per day. The proposed method
      was successfully applied for pharmacokinetic study in beagle dogs.

PMID- 29577356
TI  - Ser-486/491 phosphorylation and inhibition of AMPKalpha activity is positively
      associated with Gleason score, metastasis, and castration-resistance in prostate
      cancer: A retrospective clinical study.
AB  - BACKGROUND: We previously demonstrated that adenosine monophosphate-activated
      protein kinase (AMPKalpha) activity is significantly inhibited by Ser-486/491
      phosphorylation in cell culture and in vivo models of metastatic and castration
      resistant prostate cancer, and hypothesized these findings may translate to
      clinical specimens. METHODS: In this retrospective, single-institution pilot
      study, 45 metastatic prostate cancer cases were identified within the University
      Hospitals Cleveland Medical Center Pathology Archive with both metastasis and
      matched primary prostate tumor specimens in formalin-fixed, paraffin-embedded
      blocks, and complete electronic medical records. Thirty non-metastatic, hormone
      dependent prostate cancer controls, who were progression-free as defined by
      undetectable prostate specific antigen for at least 79.6 months (range 79.6-136.0
      months), and matched metastatic cases based on age, race, and year of diagnosis.
      All specimens were collected from 1991 to 2014; primary tumor specimens were
      obtained via diagnostic biopsy or prostatectomy, and metastasis specimens
      obtained via surgery or perimortem. 5-MU sequential slides were processed for
      phospho-Ser-486/491 AMPKalpha1 /alpha2 , phospho-Thr-172 AMPKalpha, AMPKalpha1
      /alpha2 , phospho-Ser-792 Raptor, phospho-Ser-79 acetyl-CoA carboxylase, and
      phospho-Ser-872, 3-hydroxy-3-methylglutaryl-CoA reductase immunohistochemistry to
      determine expression, phosphorylation pattern, and activity of AMPKalpha.
      RESULTS: Increased inhibitory Ser-486/491 AMPKalpha1 /alpha2 phosphorylation,
      increased AMPKalpha protein expression, decreased AMPKalpha activity, and loss of
      nuclear AMPKalpha and p-AMPKalpha are associated with prostate cancer progression
      to metastasis. Increased p-Ser-486/491 AMPKalpha1 /alpha2 was also positively
      correlated with higher Gleason grade and progression to castration-resistance.
      CONCLUSIONS: p-Ser-486/491 AMPKalpha1 /alpha2 is a novel marker of prostate
      cancer metastasis and castration-resistance. Ser-486/491 phosphokinases should be
      pursued as targets for metastatic and castration-resistant prostate cancer
      chemotherapy.

PMID- 29577357
TI  - Rationale and design of the FELICITAR registry (Frailty Evaluation After List
      Inclusion, Characteristics and Influence on Transplantation and Results).
AB  - Frailty reflects a state of decreased physiological reserve and vulnerability to
      stressors. Its prevalence among patients with cardiovascular disease is as high
      as 60%. Frailty is associated with a poor prognosis for patients with heart
      failure, increasingly frequent hospitalization, and death. The recent published
      listing criteria for heart transplantation of the International Society for Heart
      and Lung Transplantation recommend assessing frailty (class IIb recommendation,
      level of evidence C). However, this recommendation is not based on prospective
      studies, and frailty scores have only been validated in patients age > 65 years.
      The aim of the FELICITAR registry (Frailty Evaluation After List Inclusion,
      Characteristics and Influence on Transplantation and Results) is to assess the
      impact of frailty on prognosis before and after heart transplantation. A series
      of 100 patients from 3 Spanish centers will be included as soon as they are added
      to the national heart transplantation waiting list. Frailty will be evaluated
      again every 3 months until heart transplantation and at 3, 6, and 12 months
      thereafter. Depression, cognitive assessment, and quality of life also will be
      analyzed. The 2 primary endpoints are all-cause mortality and prevalence of
      frailty assessed using the Fried frailty index. Results from this study may show
      that frailty is frequent in patients with advanced heart failure listed for heart
      transplantation and is associated with a poor prognosis both before and after
      surgery. The findings may contribute to a better understanding of the
      characteristics of the optimal candidate for heart transplantation.

PMID- 29577358
TI  - Simultaneous determination of six coptis alkaloids in urine and feces by LC-MS/MS
      and its application to excretion kinetics and the compatibility mechanism of Jiao
      Tai-Wan in insomniac rats.
AB  - Jiao-Tai-Wan (JTW) is a well-known traditional Chinese medicine prescription
      composed of Rhizoma Coptidis (RC) and Cortex Cinnamon (10:1, g/g). It has been
      used to treat insomnia in China for centuries. This study investigates the
      excretion properties of coptis alkaloids from RC and JTW in normal and insomniac
      rats, and it examines the compatibility mechanism for this prescription. A new
      liquid chromatography-tandem mass spectrometry method was developed for the
      simultaneous determination of six alkaloids - berberine, epiberberine, coptisine,
      jatrorrhizine, palmatine and magnoflorine - in rat urine and feces. The normal
      and model rats were orally treated with RC and JTW powder at a dosage containing
      3.0 g kg-1  day-1 RC once per day for 7 days. Briefly, the results showed that
      the cumulative amounts of urinary and fecal excretion of the six alkaloids were
      significantly different in the pathological condition, as well as in
      compatibility. In normal rats, the urinary and fecal excretion of coptis
      alkaloids, especially berberine, coptisine and palmatine, increased significantly
      in the JTW group compared with the RC group, while the urinary and fecal
      excretion of six alkaloids decreased in insomniac rats. These data suggested that
      pathological conditions might have a notable influence on the excretion of
      alkaloids in rats, and demonstrated that the compatibility could promote better
      therapeutic effects through the accumulation of alkaloids in the body. These
      results might explain the compatibility of JTW.

PMID- 29577359
TI  - NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic
      nucleus neurons in a parkinsonian nonhuman primate.
AB  - N-methyl-D-aspartate receptors (NMDARs) are ion channels comprising tetrameric
      assemblies of GluN1 and GluN2 receptor subunits that mediate excitatory
      neurotransmission in the central nervous system. Of the four different GluN2
      subunits, the GluN2D subunit-containing NMDARs have been suggested as a target
      for antiparkinsonian therapy because of their expression pattern in some of the
      basal ganglia nuclei that show abnormal firing patterns in the parkinsonian
      state, specifically the subthalamic nucleus (STN). In this study, we demonstrate
      that blockade of NMDARs altered spike firing in the STN in a male nonhuman
      primate that had been rendered parkinsonian by treatment with the neurotoxin 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In accompanying experiments in male
      rodents, we found that GluN2D-NMDAR expression in the STN was reduced in acutely
      or chronically dopamine-depleted animals. Taken together, our data suggest that
      blockade of NMDARs in the STN may be a viable antiparkinsonian strategy, but that
      the ultimate success of this approach may be complicated by parkinsonism
      associated changes in NMDAR expression in the STN.

PMID- 29577360
TI  - Systematic review with meta-analysis: combination treatment of regimens based on
      pegylated interferon for chronic hepatitis B focusing on hepatitis B surface
      antigen clearance.
AB  - BACKGROUND: The seroclearance of hepatitis B surface antigen (HBsAg) in patients
      with chronic hepatitis B (CHB) is considered to be associated with favourable
      clinical outcomes. AIMS: This meta-analysis was performed to establish the
      proportion of HBsAg loss rates among CHB patients who received combination
      treatment based on pegylated interferon (PegIFN). Four combination strategies
      have been studied with the aim of improving HBsAg loss: "de novo," "NA
      experienced," "switch-to" and "add-on." This meta-analysis was performed to
      determine which, if any, of these combination strategies was more effective.
      METHODS: Medline, Web of Science and Embase databases were searched from
      inception to December 2017. The proportion of patients who achieved HBsAg loss
      after combination therapy was pooled using a random-effects model. RESULTS:
      Twenty-four studies fulfilled the meta-analysis criteria. The overall pooled
      proportion suggested that the rate of HBsAg loss could be increased to 9% (95%
      CI: 7%-12%) based on the combination treatment in CHB patients. Compared with "de
      novo" strategy (8%, 95% CI: 6%-10%), the "nucleos(t)ide analogues-experienced"
      (11%, 95% CI: 8%-15%) was found to be more likely (P = 0.036) to achieve a
      response. Compared with the "add-on" strategy (8%, 95% CI: 5%-13%), the "switch
      to" (14%, 95% CI: 9%-20%) was found to be more likely (P = 0.012) to achieve
      HBsAg loss. CONCLUSION: The "nucleos(t)ide analogues-experienced" strategy was
      more effective than the "De novo" strategy in achieving HBsAg loss for CHB
      patients. Combination treatment using regimens based on Peg-IFN may be useful to
      help nucleos(t)ide analogues-treated patients, who have experienced at least 48
      weeks of nucleot(s)ide analogue, achieve HBsAg seroclearance.

PMID- 29577361
TI  - Corrigendum for Peng, Zhou, Xie, et al. (2017) DOI: 10.1002/pd.5015.

PMID- 29577362
TI  - Efficacy of biofeedback therapy on sleep bruxism: A systematic review and meta
      analysis.
AB  - This study updates the review published by Wang et al in 2014 (Sleep Breath
      2014;18(2):235-242). The review focuses on the most recent literature on
      management of sleep bruxism (SB) with biofeedback. An electronic search was
      conducted in five databases searching for articles published later than the date
      of Wang et al's search, viz., October 2012. Six articles of 2320 identified
      citations involving 86 adult participants were included in the qualitative
      synthesis. Of them, 4 were randomised controlled trials (RCTs) and 2 were
      uncontrolled before-after studies. Different feedback modalities (electrical,
      auditory and vibratory stimulus) were investigated. The overall quality of the
      selected studies was assessed using the GRADE criteria. Due to heterogeneity
      between studies, the quantitative synthesis was performed out of three RCTs, of
      which two were retrieved from the previous review. The meta-analysis indicated a
      non-significant difference in electromyographic-measured SB episodes per hour
      after one night of contingent electrical stimulation (CES) compared with placebo
      control, yet a significant difference was shown after five nights of CES. The
      quality of evidence identified through GRADEpro was from low to moderate, due to
      imprecision and inconsistency between studies. Qualitative synthesis did not
      present a reliable reduction in clinical pain levels; however, no substantial
      sleep disturbances were indicated following the intervention. In conclusion, one
      of the biofeedback modalities, CES, is effective in reducing SB-related motor
      activities after a short-term treatment period. However, evidence of long-term
      effects is lacking. Further longitudinal studies with larger samples are
      necessary to acknowledge the clinical application of biofeedback.

PMID- 29577363
TI  - Relative efficiency of unequal versus equal cluster sizes in cluster randomized
      trials using generalized estimating equation models.
AB  - There is growing interest in conducting cluster randomized trials (CRTs). For
      simplicity in sample size calculation, the cluster sizes are assumed to be
      identical across all clusters. However, equal cluster sizes are not guaranteed in
      practice. Therefore, the relative efficiency (RE) of unequal versus equal cluster
      sizes has been investigated when testing the treatment effect. One of the most
      important approaches to analyze a set of correlated data is the generalized
      estimating equation (GEE) proposed by Liang and Zeger, in which the "working
      correlation structure" is introduced and the association pattern depends on a
      vector of association parameters denoted by rho. In this paper, we utilize GEE
      models to test the treatment effect in a two-group comparison for continuous,
      binary, or count data in CRTs. The variances of the estimator of the treatment
      effect are derived for the different types of outcome. RE is defined as the ratio
      of variance of the estimator of the treatment effect for equal to unequal cluster
      sizes. We discuss a commonly used structure in CRTs-exchangeable, and derive the
      simpler formula of RE with continuous, binary, and count outcomes. Finally, REs
      are investigated for several scenarios of cluster size distributions through
      simulation studies. We propose an adjusted sample size due to efficiency loss.
      Additionally, we also propose an optimal sample size estimation based on the GEE
      models under a fixed budget for known and unknown association parameter (rho) in
      the working correlation structure within the cluster.

PMID- 29577364
TI  - Screening for therapeutic trials and treatment indication in clinical practice:
      MACK-3, a new blood test for the diagnosis of fibrotic NASH.
AB  - BACKGROUND: The composite histological endpoint comprising nonalcoholic
      steatohepatitis (NASH) and NAFLD activity score >=4 and advanced fibrosis (F >=
      2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is
      currently used to select patients for inclusion in phase III therapeutic trials
      and will ultimately be used to indicate treatment in clinical practice once the
      new drugs are approved. AIM: To develop a new blood test specifically dedicated
      for this new diagnostic target of interest. METHODS: Eight Hundred and forty-six
      biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were
      randomised into derivation and validation sets. RESULTS: The blood fibrosis tests
      BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC:
      0.566 +/- 0.023, 0.654 +/- 0.023, 0.732 +/- 0.021. In the derivation set,
      fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were
      combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity
      and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a
      significantly higher AUROC (0.847 +/- 0.030, P <= 0.002) than blood fibrosis
      tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the
      patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH
      with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%,
      positive predictive value: 81.8% and negative predictive value: 97.0%.
      CONCLUSION: The new blood test MACK-3 accurately diagnoses fibrotic NASH. This
      new test will facilitate patient screening and inclusion in NAFLD therapeutic
      trials and will enable the identification of patients who will benefit from the
      treatments once approved.

PMID- 29577365
TI  - Oleuropein, a component of extra virgin olive oil, lowers postprandial glycaemia
      in healthy subjects.
AB  - AIMS: Extra virgin olive oil lowers postprandial glycaemia. We investigated if
      oleuropein, a component of extra virgin olive oil, exerts a similar effect on
      postprandial glycaemia and the underlying mechanism. METHODS: Twenty healthy
      subjects were randomly allocated in a cross-over design to 20 mg oleuropein or
      placebo immediately before lunch. Postprandial glycaemia along with blood
      insulin, dipeptidyl-peptidase-4 (DPP-4) and glucagon-like peptide-1 and oxidative
      stress, which included soluble NADPH oxidase-derived peptide activity (sNox2-dp),
      8-iso-prostaglandin-2alpha and platelet p47phox phosphorylation, were analysed
      before and 2 h after meal. RESULTS: After 2 h, subjects who assumed oleuropein
      had significantly lower blood glucose, DPP-4 activity and higher insulin and
      glucagon-like peptide-1 compared to placebo. Furthermore, sNox2-dp, 8-iso
      PGF2alpha and platelet p47phox phosphorylation were significantly lower in
      oleuropein- compared to placebo-treated subjects. DPP-4 significantly correlated
      with sNox2-dp [Spearman's rho (Rs) = 0.615; P < 0.001], p47phox phosphorylation
      (Rs = 0.435; P < 0.05) and 8-iso- prostaglandin-2alpha (Rs = 0.33; P < 0.05). In
      vitro study demonstrated that hydroxytyrosol, a metabolite of oleuropein,
      significantly reduced p47phox phosphorylation and isoprostane formation.
      CONCLUSIONS: These findings indicate that oleuropein improves postprandial
      glycaemic profile via hampering Nox2-derived oxidative stress.

PMID- 29577366
TI  - Suicide Ideation in Adolescents Following Inpatient Hospitalization: Examination
      of Intensity and Lability Over 6 Months.
AB  - Understanding suicide ideation (SI) in adolescents, especially during the high
      risk time following hospitalization for a suicidal event, is a crucial component
      of improving risk assessment. Most studies rely on single assessments of SI,
      despite the potential for SI to vary considerably over time. This study examined
      how indices of SI intensity (mean values) and lability (mean squared successive
      difference values) over a 6-month period predict suicide attempts (SAs) and self
      harm, as well as how they relate to psychosocial risk factors and affective
      functioning, in a sample of 103 adolescents hospitalized for a SA or significant
      SI. Across the sample, SI intensity, but not lability, was associated with SAs
      and nonsuicidal self-injury at 6-month follow-up. SI intensity performed
      similarly to single time point SI assessments, and its relations were not
      moderated by SI lability. SI intensity was also associated with borderline
      personality disorder criteria and a history of sexual abuse. In contrast, SI
      lability was associated with greater negative affect intensity and lability.
      These findings suggest that intensity of SI may confer more risk
      posthospitalization, and provide support for using these statistical methods to
      capture two distinct parameters of SI.

PMID- 29577367
TI  - Bioluminescence-driven optogenetic activation of transplanted neural precursor
      cells improves motor deficits in a Parkinson's disease mouse model.
AB  - The need to develop efficient therapies for neurodegenerative diseases is urgent,
      especially given the increasing percentages of the population living longer, with
      increasing chances of being afflicted with conditions like Parkinson's disease
      (PD). A promising curative approach toward PD and other neurodegenerative
      diseases is the transplantation of stem cells to halt and potentially reverse
      neuronal degeneration. However, stem cell therapy does not consistently lead to
      improvement for patients. Using remote stimulation to optogenetically activate
      transplanted cells, we attempted to improve behavioral outcomes of stem cell
      transplantation. We generated a neuronal precursor cell line expressing
      luminopsin 3 (LMO3), a luciferase-channelrhodopsin fusion protein, which responds
      to the luciferase substrate coelenterazine (CTZ) with emission of blue light that
      in turn activates the opsin. Neuronal precursor cells were injected bilaterally
      into the striatum of homozygous aphakia mice, which carry a spontaneous mutation
      leading to lack of dopaminergic neurons and symptoms of PD. Following
      transplantation, the cells were stimulated over a period of 10 days by
      intraventricular injections of CTZ. Mice receiving CTZ demonstrated significantly
      improved motor skills in a rotarod test compared to mice receiving vehicle. Thus,
      bioluminescent optogenetic stimulation of transplanted neuronal precursor cells
      shows promising effects in improving locomotor behavior in the aphakia PD mouse
      model and encourages further studies to elucidate the mechanisms and long-term
      outcomes of these beneficial effects.

PMID- 29577368
TI  - Higher expression of human telomerase reverse transcriptase in productively
      infected CD4 cells possibly indicates a mechanism for persistence of the virus in
      HIV infection.
AB  - Mechanisms involved in survival of productively-infected memory CD4+cells after
      initial antigenic stimulation and their subsequent reversion to the resting state
      are critical for the development of a predominant replication-competent HIV
      reservoir. These mechanisms may also counter their elimination after HIV
      reactivation through latency-reversing agents (LRA). Thus, their evaluation is
      critical when using an appropriate HIV latency model that recapitulates the
      predominant replication-competent HIV reservoir to develop strategies for HIV
      eradication. The model for evaluating the possible survival mechanisms after T
      cell receptor (TCR) stimulation was developed by infecting memory CD4+cells with
      an HIV-1C primary isolate and cytokine secretion and gene expression patterns
      determined. Infected cells showed compromised functionality as evident from 6.8
      fold lower secretion of IL-2 than from uninfected control cells. After TCR
      stimulation, the infected cells showed significantly higher fold increases in
      CD27 and CCR5 and smaller increases in CD5 mRNA over baseline values. Because
      CD27 expression may influence telomerase activity through AKT phosphorylation,
      CD27, human telomerase reverse transcriptase (hTERT) and pAKT expression in
      productively-infected cells from HIV-infected patients was evaluated by flow
      cytometry. HIV harbored in memory CD4+ cells was reactivated by HIV-1 envelope
      peptides, which have been shown to act as effective LRA. P24+CD4+cell showed
      significantly higher expression of CD27, hTERT and pAKT than P24-CD4+cells. These
      findings indicate compromised functionality of HIV-infected cells after TCR
      stimulation, which may interfere with their elimination by the immune system.
      They also indicate that pAKT and hTERT induction are possible survival mechanisms
      of productively-infected CD4+cells.

PMID- 29577369
TI  - AldB controls persister formation in Escherichia coli depending on environmental
      stress.
AB  - Persisters are multidrug-tolerant cells that are present within antibiotic
      sensitive populations. Persister formation is not induced by genetic mutations,
      but rather by changes in the degree of expression of some genes. High redundancy
      has been observed among the pathways that have been hypothesized to respond to
      specific stresses. In this study, we conducted RNA sequencing of Escherichia coli
      persisters under various stress conditions to identify common mechanisms. We
      induced stresses such as glucose or amino acid exhaustion, acid stress and
      anaerobic conditions, all of which are encountered during bacterial pathogenesis.
      We found that most genes are differentially expressed depending on the specific
      stress condition; however, some genes were commonly expressed in persisters in
      most stress conditions. Commonly expressed genes are expected to be promising
      therapeutic targets for combating persistent infections. We found that knockdown
      of aldehyde dehydrogenase (aldB), which was expressed in every condition except
      for acid stress, decreased persisters in the non-stressed condition. However, the
      same strain unexpectedly showed an increased number of persisters in the amino
      acid-limited condition. Because the increase in persister number is glycolytic
      metabolite-dependent, metabolic flow may play a crucial role in aldB-mediated
      persister formation. These data suggest that environmental stresses alter
      persister mechanisms. Identification of environmental influences on persister
      formation during pathogenesis is therefore necessary to enabling persister
      eradication.

PMID- 29577370
TI  - Dynamic analysis of expression of chemokine and cytokine gene responses to H5N1
      and H9N2 avian influenza viruses in DF-1 cells.
AB  - H5N1 and H9N2 are the most important causes of avian influenza in China.
      Chemokines and cytokines play important roles in inflammatory response that
      clearly differ between H5N1 and H9N2 infection. To investigate whether chemokines
      and cytokines are differentially regulated following H5N1 and H9N2 AIVs
      infection, dynamic expression of chemokines and cytokines, including IL8L1,
      IL8L2, CX3CL1, CCL5, CCL20, K203, SCYA4, XLC1, CCLi10, CCL19, IFN-alpha, IFN
      beta, IL-1beta, IL-6 and TNF-alpha, were analyzed by real-time quantitative RT
      PCR in DF-1 cells. It was found that IL8L1, IL8L2, CX3CL1, CCL5, CCL20, K203,
      SCYA4, IFN-alpha, IFN-beta, IL-1beta, IL-6 and TNF-alpha increased significantly
      after induction of H5N1 or H9N2 AIV infection, whereas no expression of XCL1,
      CCLi10 or CCL19 was detected. H9N2 AIV infection was associated with much
      stronger chemokine responses than infection with H5N1, whereas the cytokines
      showed opposite results. It was found that K203 is a constant chemotactic factor
      independent of subtype of AIVs and infectious dose, CCL20 and IL-1beta are
      constant regardless of the infectious dose but depend on the subtype of AIV,
      chemotactic factors IL8L1, IL8L2 and CCL5 are dependent both on subtype of AIVs
      and infectious dose, and K203, CX3CL1, SCYA4, CCL20, IFN-alpha, IL-1beta and TNF
      alpha are specific to responses to H5N1 AIV infection whereas K203, CCL20, IFN
      beta, IL-1beta and IL-6 are specific to H9N2 infection. These results provide
      basic data for explaining differences in inflammation and phenotypes of
      histopathological changes caused by H5N1 and H9N2 and add new information on the
      roles of chemokines and cytokines in virulence of AIVs.

PMID- 29577371
TI  - Role of T-bet, the master regulator of Th1 cells, in the cytotoxicity of murine
      CD4+ T cells.
AB  - Although CD4+ T cells are generally regarded as helper T cells, some activated
      CD4+ T cells have cytotoxic properties. Given that CD4+ cytotoxic T lymphocytes
      (CTLs) often secrete IFN-gamma, CTL activity among CD4+ T cells may be
      attributable to Th1 cells, where a T-box family molecule, T-bet serves as the
      "master regulator". However, although the essential contribution of T-bet to
      expression of IFN-gamma has been well-documented, it remains unclear whether T
      bet is involved in CD4+ T cell-mediated cytotoxicity. In this study, to
      investigate the ability of T-bet to confer cytolytic activity on CD4+ T cells,
      the T-bet gene (Tbx21) was introduced into non-cytocidal CD4+ T cell lines and
      their cytolytic function analyzed. Up-regulation of FasL (CD178), which provided
      the transfectant with cytotoxicity, was observed in Tbx21transfected CD4+ T cells
      but not in untransfected parental cells. In one cell line, T-bet transduction
      also induced perforin gene (Prf1) expression and Tbx21 transfectants efficiently
      killed Fas- target cells. Although T-bet was found to repress up-regulation of
      CD40L (CD154), which controls FasL-mediated cytolysis, the extent of CD40L up
      regulation on in vitro-differentiated Th1 cells was similar to that on Th2 cells,
      suggesting the existence of a compensatory mechanism. These results collectively
      indicate that T-bet may be involved in the expression of genes, such as FasL and
      Prf1, which confer cytotoxicity on Th1 cells.

PMID- 29577372
TI  - Effect of tadalafil on chronic pelvic pain and prostatic inflammation in a rat
      model of experimental autoimmune prostatitis.
AB  - BACKGROUND: Experimental autoimmune prostatitis (EAP) shares important clinical
      features with clinical chronic prostatitis/chronic pelvic pain. We investigated
      the effect of tadalafil on pelvic pain and prostatic inflammation in a rat EAP
      model. METHODS: EAP was induced in rats by intradermal injection of rat prostate
      antigen and complete Freund's adjuvant on days 0 and 28. Rats were treated with
      tadalafil (2 mg/kg, p.o.; EAP-tadalafil) or vehicle (EAP-vehicle) once daily from
      day 0, while sham-operated animals were treated with vehicle only (Sham). Tactile
      allodynia was measured on days 28, 35, and 42 by applying von Frey filaments to
      the lower abdomen as an index of pelvic pain. On day 42, the plasma
      immunoglobulin G (IgG) concentration and the testosterone/estradiol ratio were
      measured and histopathological analysis of the prostate was performed. RESULTS:
      Tactile allodynia in the pelvic region was observed on days 28, 35, and 42 after
      EAP induction. The tactile allodynia observed on day 42 was significantly reduced
      by repeated treatment with tadalafil. Plasma IgG concentrations increased after
      EAP induction but the increase was not changed by tadalafil treatment. Prostate
      tissues were characterized by epithelial necrosis, infiltration of neutrophils
      and/or lymphocytes to acini and stroma, and fibrosis, in addition to a high
      stroma-to-epithelium ratio. Tadalafil treatment significantly suppressed the
      severity of the lesions. CONCLUSIONS: EAP rats developed pelvic pain, prostatic
      inflammation and increased plasma IgG concentrations. Tadalafil inhibited the
      chronic pelvic pain and prostatic inflammation, suggesting that its anti
      inflammatory action may contribute to its blocking of pain development in the EAP
      model.

PMID- 29577373
TI  - Understanding the regulation of neural stem cell proliferation in Drosophila
      central nervous system.

PMID- 29577374
TI  - Comparison of behavioral, neuroprotective, and proinflammatory cytokine
      modulating effects exercised by (+)-cis-EC and (-)-cis-EC stereoisomers in a PTZ
      induced kindling test in mice.
AB  - Epoxy-carvone (EC) has chiral centers that allow generation of stereoisomers,
      including (+)-cis-EC and (-)-cis-EC, whose effects in the kindling tests have
      never been studied. Accordingly, this study aims to comparatively investigate the
      effect of stereoisomers (+)-cis-epoxy-carvone and (-)-cis-epoxy-carvone on
      behavioral changes measured in scores, in the levels of cytokines (IL-1beta, IL
      6, and TNFalpha) and neuronal protection in the face of continuous treatment with
      pentylenetetrazol. Swiss mice were divided into five groups (n = 10), receiving
      vehicle, (+) - cis-EC, (-) - cis-EC (both at the dose of 30 mg/kg), and diazepam
      (4 mg/kg). Thirty minutes after the respective treatment was administered to the
      animals one subconvulsive dose of PTZ (35 mg/kg). Seven subconvulsives treatments
      were made on alternate days, in which each treatment several parameters were
      recorded. In the eighth treatment, the animals receiving the highest dose of PTZ
      (75 mg/kg) and were sacrificed for quantification of cytokines and
      histopathologic analysis. All drugs were administered by intraperitoneal route.
      In the kindling test, (+)-cis-EC and (-)-cis-EC reduced the average scores. The
      stereoisomer (+)-cis-EC decreased levels of proinflammatory cytokines IL-1beta,
      IL-6, and TNFalpha, whereas comparatively (-)-cis-EC did not reduce IL-1beta
      levels. Histopathological analysis of the mice hippocampi undergoing this
      methodology showed neural protection for treated with (+)-cis-EC. The results
      suggest that the anticonvulsant effect of (+)-cis-EC possibly takes place due to
      reduction of proinflammatory cytokines involved in the epileptogenic process,
      besides neuronal protection, yet further investigation of the mechanisms involved
      is required.

PMID- 29577375
TI  - Ca2+/calmodulin-dependent protein kinase II and Dimethyl Sulfoxide affect the
      sealing frequencies of transected hippocampal neurons.
AB  - Traumatic injury often results in axonal severance, initiating obligatory
      Wallerian degeneration of distal segments, whereas proximal segments often
      survive. Calcium ion (Ca2+ ) influx at severed proximal axonal ends activates
      pathways that can induce apoptosis. However, this same Ca2+ -influx also
      activates multiple parallel pathways that seal the plasmalemma by inducing
      accumulation and fusion of vesicles at the lesion site that reduce Ca2+ -influx
      and enhance survival. We examined whether various inhibitors of Ca2+ /calmodulin
      dependent protein kinases (CaMKs), and/or dimethyl sulfoxide (DMSO), a common
      solvent for biologically active substances, affected the ability of a hippocampal
      derived neuronal cell line (B104 cells) to seal membrane damage following
      axotomy. Axolemmal sealing frequencies were assessed at different transection
      distances from the axon hillock and at various times after Ca2+ -influx (PC
      times) by observing whether transected cells took-up fluorescent dyes. Inhibition
      of CaMKII by tatCN21 and KN-93, but not inhibition of CaMKI and CaMKIV by STO
      609, affected axonal sealing frequencies. That is, CaMKII is a component of
      previously reported parallel pathways that induce membrane sealing, whereas CaMKI
      and CaMKIV are not involved. The effects of these CaMKII inhibitors on
      plasmalemmal sealing depended on their mechanism of inhibition, transection
      distance, and PC time. DMSO at low concentrations (90 uM-28 mM or 0.00064%-0.2%
      v/v) significantly increased membrane-sealing frequencies at most PC times and
      transection distances, possibly by permeabilizing the plasmalemma to Ca2+ .
      Inhibition of CaMKII, DMSO, PC time, and the transection distance significantly
      affect plasmalemmal sealing that is critical to somal survival in traumatic
      lesions.

PMID- 29577376
TI  - Dynamic prediction of cumulative incidence functions by direct binomial
      regression.
AB  - In recent years there have been a series of advances in the field of dynamic
      prediction. Among those is the development of methods for dynamic prediction of
      the cumulative incidence function in a competing risk setting. These models
      enable the predictions to be updated as time progresses and more information
      becomes available, for example when a patient comes back for a follow-up visit
      after completing a year of treatment, the risk of death, and adverse events may
      have changed since treatment initiation. One approach to model the cumulative
      incidence function in competing risks is by direct binomial regression, where
      right censoring of the event times is handled by inverse probability of censoring
      weights. We extend the approach by combining it with landmarking to enable
      dynamic prediction of the cumulative incidence function. The proposed models are
      very flexible, as they allow the covariates to have complex time-varying effects,
      and we illustrate how to investigate possible time-varying structures using Wald
      tests. The models are fitted using generalized estimating equations. The method
      is applied to bone marrow transplant data and the performance is investigated in
      a simulation study.

PMID- 29577377
TI  - Improved calculation of the equilibrium magnetization of arterial blood in
      arterial spin labeling.
AB  - PURPOSE: To propose and assess an improved method for calculating the equilibrium
      magnetization of arterial blood ( M0a), used for calibration of perfusion
      estimates in arterial spin labeling. METHODS: Whereas standard M0a calculation is
      based on dividing a proton density-weighted image by an average brain-blood
      partition coefficient, the proposed method exploits partial-volume data to adjust
      this ratio. The nominator is redefined as the magnetization of perfused tissue,
      and the denominator is redefined as a weighted sum of tissue-specific partition
      coefficients. Perfusion data were acquired with a pseudo-continuous arterial spin
      labeling sequence, and partial-volume data were acquired using a rapid saturation
      recovery sequence with the same readout module. Results from 7 healthy volunteers
      were analyzed and compared with the conventional method. RESULTS: The proposed
      method produced improved M0a homogeneity throughout the brain in all subjects.
      The mean gray matter perfusion was significantly higher with the proposed method
      compared with the conventional method: 61.2 versus 56.3 mL/100 g/minute (+8.7%).
      Although to a lesser degree, the corresponding white matter values were also
      significantly different: 20.8 versus 22.0 mL/100 g/minute (-5.4%). The spatial
      and quantitative differences between the 2 methods were similar in all subjects.
      CONCLUSION: Compared with the conventional approach, the proposed method produced
      more homogenous M0a maps, corresponding to a more accurate calibration. The
      proposed method also yielded significantly different perfusion values across the
      whole brain, and performed consistently in all subjects. The new M0a method
      improves quantitative perfusion estimation with arterial spin labeling, and can
      therefore be of considerable value in perfusion imaging applications.

PMID- 29577378
TI  - Relationship between alcohol consumption and periodontal tissue condition in
      community-dwelling elderly Japanese.
AB  - OBJECTIVES: To examine the associations among alcohol consumption level, dietary
      intake and other lifestyle factors, and periodontal condition, in community
      dwelling elderly Japanese of a specific age. BACKGROUND: The relationship between
      alcohol consumption level and periodontitis is a controversial issue. METHODS:
      Participants were 438 dentate elders aged 73 years from a larger cohort survey of
      elders in Niigata City, Japan. Data collected from oral examination of each
      participant, including number of the existing teeth, mean probing pocket depth
      and mean clinical attachment level (CAL) were used for the analyses. A
      semiquantitative food frequency questionnaire and a lifestyle habit questionnaire
      were used to assess food and alcohol consumption, smoking experience, frequency
      of tooth brushing, interdental brush use, and visits to a dental clinic during
      the previous year. Blood glucose control was assessed by the glycated haemoglobin
      (HbA1c) level. Body mass index was calculated from height and weight
      measurements. The relationships between each variable and the individual mean CAL
      were analysed by univariate and multivariate analyses. RESULTS: According to
      logistic regression analysis, the mean CAL was significantly associated with the
      number of existing teeth (odds ratio [OR] = 0.90; P < .001), being a heavy
      drinker (OR = 2.44; P < .05), and smoking experience (OR = 2.37; P < .01).
      CONCLUSION: This study showed that increased mean CAL was significantly
      associated with heavy drinking in community-dwelling elderly Japanese (aged 73
      years) compared with non-drinking. Our results provide new evidence that high
      alcohol consumption is associated with an increased risk of periodontal disease
      and its progression.

PMID- 29577379
TI  - A free anterolateral thigh flap for pharyngeal reconstruction following dynamic
      hip screw femur fixation.

PMID- 29577380
TI  - The effect of medical and operative birth interventions on child health outcomes
      in the first 28 days and up to 5 years of age: A linked data population-based
      cohort study.
AB  - BACKGROUND: Spontaneous vaginal birth rates are decreasing worldwide, while
      cesarean delivery, instrumental births, and medical birth interventions are
      increasing. Emerging evidence suggests that birth interventions may have an
      effect on children's health. Therefore, the aim of our study was to examine the
      association between operative and medical birth interventions on the child's
      health during the first 28 days and up to 5 years of age. METHODS: In New South
      Wales (Australia), population-linked data sets were analyzed, including data on
      maternal characteristics, child characteristics, mode of birth, interventions
      during labor and birth, and adverse health outcomes of the children (ie,
      jaundice, feeding problems, hypothermia, asthma, respiratory infections,
      gastrointestinal disorders, other infections, metabolic disorder, and eczema)
      registered with the International Statistical Classification of Diseases and
      Related Health Problems, Tenth Revision, Australian Modification codes. Logistic
      regression analyses were performed for each adverse health outcome. RESULTS: Our
      analyses included 491 590 women and their children; of those 38% experienced a
      spontaneous vaginal birth. Infants who experienced an instrumental birth after
      induction or augmentation had the highest risk of jaundice, adjusted odds ratio
      (aOR) 2.75 (95% confidence interval [CI] 2.61-2.91) compared with spontaneous
      vaginal birth. Children born by cesarean delivery were particularly at
      statistically significantly increased risk for infections, eczema, and metabolic
      disorder, compared with spontaneous vaginal birth. Children born by emergency
      cesarean delivery showed the highest association for metabolic disorder, aOR 2.63
      (95% CI 2.26-3.07). CONCLUSION: Children born by spontaneous vaginal birth had
      fewer short- and longer-term health problems, compared with those born after
      birth interventions.

PMID- 29577381
TI  - Remote Mentoring of Point-of-Care Ultrasound Skills to Inexperienced Operators
      Using Multiple Telemedicine Platforms: Is a Cell Phone Good Enough?
AB  - OBJECTIVES: Telemedicine technology contributes to the teaching of point-of-care
      ultrasound (US); however, expensive equipment can limit its deployment in
      resource-challenged settings. We assessed 3 low-cost telemedicine solutions
      capable of supporting remote US training to determine feasibility, acceptability,
      and effectiveness. We also explored the value of instructional videos immediately
      before telementoring. METHODS: Thirty-six participants were randomly assigned to
      receive US mentoring in 1 of 3 telemedicine conditions: multiple fixed cameras, a
      smartphone, and traditional audio with a live US stream. Participants were then
      asked to perform a standardized US examination of the right upper quadrant under
      remote guidance. We measured observer's global ratings of performance along with
      the mentor's and student's rating of effort and satisfaction to determine which
      of the 3 approaches was most feasible, acceptable, and effective. During the
      second phase, students were randomized to watch an instructional video or not
      before receiving remote coaching on how to complete a subxiphoid cardiac
      examination. Effort, satisfaction, and performance from the independent
      observer's and student's perspective were surveyed. RESULTS: There was no
      significant difference between the different telemedicine setups from the
      observer's perspective; however, the mentor rated the smartphone significantly
      worse (P = .028-.04) than other technologies. Platforms were rated equivalent
      from the student's perspective. No benefit was detected for watching an
      instructional video before the mentored task. CONCLUSIONS: Remote US skills can
      be taught equally effectively by using a variety of telemedicine technologies.
      Smartphones represent a viable option for US training in resource-challenged
      settings.

PMID- 29577382
TI  - MRI detection of bacterial brain abscesses and monitoring of antibiotic treatment
      using bacCEST.
AB  - PURPOSE: To develop a new MRI method to detect and characterize brain abscesses
      using the CEST contrast inherently carried by bacterial cells, namely bacCEST.
      METHODS: Bacteria S. aureus (ATCC #49775) and F98 and 9L glioma cells were
      injected stereotactically in the brains of F344 rats to form abscesses and
      tumors. The CEST signals of brain abscesses (n = 4) and tumors (n = 7) were
      acquired using 2 B1 values (i.e., 1 and 3 uT) and compared. The bacCEST signal of
      the brain abscesses in the rats (n = 3) receiving ampicillin (intraperitoneal
      injection 40 mg/kg twice daily) was acquired before, 4 and 10 days after the
      treatment. RESULTS: The bacCEST signal of S. aureus was characterized in vitro as
      a strong and broad signal in the range of 1 to 4 ppm, with the maximum contrast
      occurring at 2.6 ppm. The CEST signal in S. aureus-induced brain abscesses was
      significantly higher than that of contralateral parenchyma (p = .003). Moreover,
      thanks to their different B1 independence, brain abscesses and tumors could be
      effectively differentiated (p = .005) using DeltaCEST(2.6 ppm, 3 uT-1 uT),
      defined by the difference between the CEST signal (offset = 2.6 ppm) acquired
      using B1  = 3 uT and that of 1 uT. In treated rats, bacCEST MRI could detect the
      response of bacteria as early as 4 days after the antibiotic treatment (p =
      .035). CONCLUSION: BacCEST MRI provides a new imaging method to detect,
      discriminate, and monitor bacterial infection in deep-seated organs. Because no
      contrast agent is needed, such an approach has a great translational potential
      for detecting and monitoring bacterial infection in deep-seated organs.

PMID- 29577405
TI  - Smooth individual level covariates adjustment in disease mapping.
AB  - Spatial models for disease mapping should ideally account for covariates measured
      both at individual and area levels. The newly available "indiCAR" model fits the
      popular conditional autoregresssive (CAR) model by accommodating both individual
      and group level covariates while adjusting for spatial correlation in the disease
      rates. This algorithm has been shown to be effective but assumes log-linear
      associations between individual level covariates and outcome. In many studies,
      the relationship between individual level covariates and the outcome may be non
      log-linear, and methods to track such nonlinearity between individual level
      covariate and outcome in spatial regression modeling are not well developed. In
      this paper, we propose a new algorithm, smooth-indiCAR, to fit an extension to
      the popular conditional autoregresssive model that can accommodate both linear
      and nonlinear individual level covariate effects while adjusting for group level
      covariates and spatial correlation in the disease rates. In this formulation, the
      effect of a continuous individual level covariate is accommodated via penalized
      splines. We describe a two-step estimation procedure to obtain reliable estimates
      of individual and group level covariate effects where both individual and group
      level covariate effects are estimated separately. This distributed computing
      framework enhances its application in the Big Data domain with a large number of
      individual/group level covariates. We evaluate the performance of smooth-indiCAR
      through simulation. Our results indicate that the smooth-indiCAR method provides
      reliable estimates of all regression and random effect parameters. We illustrate
      our proposed methodology with an analysis of data on neutropenia admissions in
      New South Wales (NSW), Australia.

PMID- 29577404
TI  - High-throughput measurement of recombination rates and genetic interference in
      Saccharomyces cerevisiae.
AB  - Allelic recombination owing to meiotic crossovers is a major driver of genome
      evolution, as well as a key player for the selection of high-performing genotypes
      in economically important species. Therefore, we developed a high-throughput and
      low-cost method to measure recombination rates and crossover patterning
      (including interference) in large populations of the budding yeast Saccharomyces
      cerevisiae. Recombination and interference were analysed by flow cytometry, which
      allows time-consuming steps such as tetrad microdissection or spore growth to be
      avoided. Moreover, our method can also be used to compare recombination in wild
      type vs. mutant individuals or in different environmental conditions, even if the
      changes in recombination rates are small. Furthermore, meiotic mutants often
      present recombination and/or pairing defects affecting spore viability but our
      method does not involve growth steps and thus avoids filtering out non-viable
      spores.

PMID- 29577407
TI  - Echocardiographic and clinical markers of left ventricular ejection fraction and
      moderate or greater systolic dysfunction in left ventricular noncompaction
      cardiomyopathy.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) is associated with progressive
      LV systolic dysfunction and dilated cardiomyopathy. We aimed to investigate the
      echocardiographic and clinical characteristics associated with LV ejection
      fraction (LVEF) and moderate or greater systolic dysfunction in patients with
      LVNC. METHODS: Our institutional echocardiography database was retrospectively
      reviewed between 2008 and 2014, and 62 patients with LVNC were identified. Forty
      three (69%) had moderate or greater LV systolic dysfunction (LVEF <= 40%) and
      were compared with 19 (31%) patients with preserved or mildly reduced LVEF
      (>40%). Linear regression analyses were utilized to identify markers associated
      with LVEF. RESULTS: The mean age was 63 +/- 17 years and noncompacted-to
      compacted ratio was 2.3 +/- 0.5, and was larger in patients with LVEF <= 40% (2.4
      vs 2.1; P = .02). Patients with LVEF <= 40% were older, had more congestive heart
      failure, significant QRS interval prolongation, and greater LV remodeling and
      worse mean global longitudinal strain (GLS). Multivariate regression analysis
      revealed increased age (standardized regression coefficient (beta) = -0.17; P =
      .04) and QRS duration (beta = -0.13; P = .08), congestive heart failure (beta = 
      0.18; P = .04), and worsened GLS (beta = -0.40; P = .001) were independently
      associated with decreased LVEF in the cohort (overall model fit R2  = 0.71; P <
      .0001). Increased age (beta = -0.49; P = .01) and QRS duration (beta = -0.50; P =
      .002), and worsened GLS (beta = -0.33; P = .04), were also associated with a
      lower LVEF in patients with LVEF > 40%. CONCLUSIONS: The independent markers
      associated with LVEF and moderate or greater LV systolic dysfunction in patients
      with LVNC, in particular GLS and QRS duration, may detect high-risk candidates
      for more aggressive clinical surveillance and medical therapy.

PMID- 29577406
TI  - Quantifying myofiber integrity using diffusion MRI and random permeable barrier
      modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice.
AB  - PURPOSE: To measure the microstructural changes during skeletal muscle growth and
      progressive pathologies using the random permeable model with diffusion MRI, and
      compare findings to conventional imaging modalities such as three-point Dixon and
      T2 imaging. METHODS: In vivo and ex vivo DTI experiments with multiple diffusion
      times (20-700 ms) were completed on wild-type (n = 22) and muscle-dystrophic mdx
      mice (n = 8) at various developmental time points. The DTI data were analyzed
      with the random permeable model framework that provides estimates of the
      unrestricted diffusion coefficient (D0 ), membrane surface-to-volume ratio (S/V),
      and membrane permeability (kappa). In addition, the MRI experiments included
      conventional measures, such as tissue fat fractions and T2 relaxation. RESULTS:
      During normal muscle growth between week 4 and week 13, the in vivo S/V,
      fractional anisotropy, and fat fraction correlated positively with age (rho =
      0.638, 0.664, and 0.686, respectively), whereas T2 correlated negatively (rho = 
      0.847). In mdx mice, all DTI random permeable model parameters and fat fraction
      had significant positive correlation with age, whereas fractional anisotropy and
      T2 did not have significant correlation with age. Histological measurements of
      the perimeter-to-area ratio served as a proxy for the model-derived S/V in the
      cylindrical myofiber geometry, and had a significant correlation with the ex vivo
      S/V (r = 0.71) as well as the in vivo S/V (r = 0.56). CONCLUSION: The present
      study demonstrates that DTI at multiple diffusion times with the random permeable
      model analysis allows for noninvasively quantifying muscle fiber microstructural
      changes during both normal muscle growth and disease progression. Future studies
      can apply our technique to evaluate current and potential treatments to muscle
      myopathies.

PMID- 29577408
TI  - The role of intraoperative epicardial echocardiography in pediatric cardiac
      surgery.
AB  - AIM: Our aim was to evaluate the findings and the role of intraoperative
      epicardial echocardiography (IEE) in the management of pediatric cardiac surgery
      patients. METHODS: Patients evaluated with IEE between December 2015 and December
      2017 were analyzed retrospectively. Demographic data, preoperative transthoracic
      echocardiography (TTE), and IEE reports were evaluated. RESULTS: A total of 410
      patients evaluated by IEE were included in the study. Of these, 52% were women,
      and 48% were men. The median age was 8.5 months (range: 1 month-7 years), and
      median body weight was 7.1 kg (range: 3.3-61 kg). The most common diagnoses were
      tetralogy of Fallot (TOF; n = 148), ventricular septal defect (VSD; n = 117),
      atrial septal defect (ASD; n = 57), and complete atrioventricular septal defect
      (AVSD; n = 48). There were minor residual lesions not requiring reestablishment
      of cardiopulmonary bypass (CPB) in 16.6% (n = 68), while major residual lesions
      requiring return to CPB were determined in 5.1% (n = 21). Major residual lesions
      were detected in 7 patients with TOF (4 severe right ventricular outflow tract
      obstructions, 2 pulmonary artery stenosis, 1 residual VSD shunt), 6 patients with
      VSD (hemodynamically significant residual shunts), and 5 patients with complete
      AVSD (3 left atrioventricular valve regurgitations, 1 right atrioventricular
      valve regurgitation, 1 left ventricular outflow tract obstruction). Transient
      bradycardia was observed in 5 patients. CONCLUSION: Intraoperative epicardial
      echocardiography provides good guidance during congenital heart surgery. IEE
      helps to clarify the surgical planning and decreases morbidity and mortality due
      to unnecessary invasive procedures, especially for pathologies involving the
      pulmonary artery and its branches, as well as for apical ventricular septal
      defects.

PMID- 29577409
TI  - Effect of treatment of symptomatic convergence insufficiency on reading in
      children: a pilot study.
AB  - BACKGROUND: To evaluate the impact of treatment of symptomatic convergence
      insufficiency using office-based vergence/accommodative therapy on reading skills
      in children. METHODS: Children (n = 44) ages nine to 17 years with symptomatic
      convergence insufficiency were administered the following four reading tests:
      Wechsler Individual Achievement Test II; Test of Word Reading Efficiency; Test of
      Silent Word Reading Fluency; and the Gray Oral Reading Test, at baseline and
      eight weeks after completion of a 16-week program of office-based
      vergence/accommodative therapy. To determine whether significant change occurred
      with therapy, change in performance was compared to zero. Treatment response was
      determined using a composite score of symptoms and signs at the conclusion of
      treatment and at the 24-week outcome visit. Participants were classified as early
      responders, late responders, or non-responders based upon whether criteria for
      successful treatment were met at the completion of 16 weeks of treatment, at the
      24-week outcome visit, or not met at either visit, respectively. RESULTS: After
      treatment for convergence insufficiency, statistically significant improvements
      were found for reading comprehension (mean = 4.2, p = 0.009) and the reading
      composite score (mean = 2.4, p = 0.016) as measured by the Wechsler Individual
      Achievement Test at the 24-week visit. These improvements were related to the
      clinical treatment outcome measures (p = 0.011) with the largest improvements
      occurring in those who were early responders to treatment. Reading speed (words
      per minute) increased significantly on the Gray Oral Reading Test (p < 0.0001).
      No significant improvements were observed for single word reading or reading
      fluency as measured by the Test of Word Reading Efficiency, the Test of Silent
      Word Reading Fluency or the Gray Oral Reading Test. CONCLUSION: Improvements in
      reading comprehension and reading composite were found after office-based
      vergence/accommodative therapy, with the greatest improvements in those who
      responded early to treatment.

PMID- 29577410
TI  - Adult care providers' perspectives on the transition to adult care for emerging
      adults with Type 1 diabetes: a cross-sectional survey.
AB  - AIMS: To assess adult diabetes care providers' current transition practices,
      knowledge about transition care, and perceived barriers to implementation of best
      practices in transition care for emerging adults with Type 1 diabetes mellitus.
      METHODS: We administered a 38-item web-based survey to adult diabetes care
      providers identified through the Quebec Endocrinologist Medical Association and
      Diabetes Quebec. RESULTS: Fifty-three physicians responded (35%). Fewer than half
      of all respondents (46%) were familiar with the American Diabetes Association's
      transition care position statement. Approximately one-third of respondents
      reported a gap of >6 months between paediatric and adult diabetes care. Most
      (83%) believed communication with the paediatric team was adequate; however, only
      56% reported receiving a medical summary and 2% a psychosocial summary from the
      paediatric provider. Respondents believed that the paediatric team should improve
      emerging adults' preparation for transition care by developing their self
      management skills and improve teaching about the differences between paediatric
      and adult-oriented care. Only 31% had a system for identifying emerging adults
      lost to follow-up in adult care. Perceived barriers included difficulty accessing
      psychosocial services, emerging adults' lack of motivation, and inadequate
      transition preparation. Most (87%) were interested in having additional
      resources, including a self-care management tool and a registry to track those
      lost to follow-up. CONCLUSIONS: Our findings highlight the need to better engage
      adult care providers into transition care practices. Despite adult physicians'
      interest in transition care, implementation of transition care recommendations
      and resources in clinical care remains limited. Enhanced efforts are needed to
      improve access to mental health services within the adult healthcare setting.

PMID- 29577411
TI  - A pneumococcal conjugate vaccination programme reduced clinically suspected
      invasive disease in unvaccinated children.
AB  - AIM: The 10-valent pneumococcal conjugate vaccine was introduced to the Finnish
      national vaccination programme for children born since June 2010. We evaluated
      the changes in the rates of clinically suspected invasive pneumococcal disease
      (IPD) in unvaccinated children to estimate the indirect herd protection impact of
      the programme. METHODS: The target cohort for this ecological before and after
      comparison were unvaccinated children born from January 2008 to May 2010 and
      ineligible for the vaccination programme, who were followed up from 2011 to 2014.
      The reference cohort was age and season-matched children born in January 2003 to
      2005 and followed up from 2006 to 2009. National data on hospital discharge codes
      compatible with IPD or unspecified sepsis were collected. RESULTS: We compared
      the follow-up periods of 2007-2009 in the reference cohort and 2012-2014 in the
      target cohort. The incidence of non-laboratory-confirmed IPD in unvaccinated
      children fell by 68%, from 47 to 15/100 000 person-years. When unspecified sepsis
      was added, the decrease was 39%, from 171 to 104/100 000 person-years. Laboratory
      confirmed IPD fell by 44%, from 15 to 8/100 000 person-years. CONCLUSION: The
      pneumococcal vaccination programme provided herd protection against clinically
      suspected IPD. The absolute reduction was almost 10-times higher than for just
      laboratory-confirmed disease.

PMID- 29577413
TI  - Extracellular vesicles as mediators of immunopathology in infectious diseases.
AB  - In the last decades, extracellular vesicles have emerged as important elements in
      cell-cell communication and as key players in disease pathogenesis via
      transmission of their cargo between different cells. Various works have described
      different subpopulations of these membrane structures, based on their cell of
      origin, biogenesis, size, biophysical properties and cargo. In addition to their
      pathophysiological role in the development and progression of different diseases
      including infectious diseases, neurodegenerative disorders and cancer,
      extracellular vesicles are now recognized for their potential as novel
      therapeutic targets and intelligent drug delivery system. Here, we have reviewed
      the most recent data on different subtypes of extracellular vesicles, focusing on
      microvesicles and exosomes and their subpopulations, their involvement in immune
      mediated pathogenesis of various infectious diseases and their role as potential
      therapeutic targets.

PMID- 29577412
TI  - Sulfated vizantin induces formation of macrophage extracellular traps.
AB  - Vizantin is an insoluble adjuvant that activates macrophages and lymphocytes.
      Recently, 2,2',3,3',4,4'-hexasulfated-vizantin (sulfated vizantin), which enables
      solubilization of vizantin, was developed by the present team. Sulfated vizantin
      was found to enhance bactericidal activity against multi-drug resistant
      Pseudomonas aeruginosa in RAW264.7 cells. In addition, spread of P. aeruginosa
      was inhibited in RAW264.7 cells treated with sulfated vizantin. When only
      sulfated vizantin and P. aeruginosa were incubated, sulfated vizantin did not
      affect growth of P. aeruginosa. Formation of DNA-based extracellular traps (ETs),
      a novel defense mechanism in several types of innate immune cells, helps to
      eliminate pathogens. In the present study, ET-forming macrophages constituted the
      majority of immune cells. Sulfated vizantin induced ET formation in RAW264.7
      cells, whereas a Ca-chelating reagent, EDTA, and T-type calcium channel blocker,
      tetrandrine, inhibited ET formation and attenuated inhibition of spread of P.
      aeruginosa in sulfated vizantin-treated cells. Thus, sulfated vizantin induces ET
      formation in phagocytic cells in a Ca-dependent manner, thus preventing spread of
      P. aeruginosa. Hence, sulfated vizantin may be useful in the management of
      infectious diseases.

PMID- 29577415
TI  - The morphology of the reproductive system in the crab Percnon gibbesi (Decapoda:
      Brachyura: Grapsoidea) reveals a new combination of characters in Thoracotremata.
AB  - Recent studies revealed a high diversity of reproductive structures in
      heterotreme brachyurans, while those of Thoracotremata seem rather uniform. Yet,
      there still is a huge lack of data in this group as only few species have been
      studied with respect to their reproductive system. The phylogenetic position of
      Percnidae is ambiguous. Recent molecular studies place it within polyphyletic
      grapsoids. We herein study the reproductive morphology of Percnon gibbesi using
      histology, scanning electron microscopy, micro-computed tomography and 3D
      reconstructions to test whether this species shows the characteristic
      thoracotreme pattern. Our results reveal that the male copulatory system conforms
      to other thoracotremes. It is composed of two pairs of pleopods (gonopods) and
      likewise paired penes. The first gonopod is relatively long. It possesses a bent
      terminal process with a distal opening of the ejaculatory canal, a character also
      present in other grapsoids. The second gonopod is short and terminates in an
      apical girdle. The female reproductive system reveals a combination of
      characters, so far unknown for thoracotremes. The paired oviducts do not lead
      into the seminal receptacles, but run into separate cuticular ducts joined with
      the vaginae. Accessory sperm storage organs, the bursae, are also connected to
      the vaginae. Bursae have previously only been described in heterotreme crabs. The
      data presented in this study reveals a higher diversity of thoracotreme
      reproductive systems than anticipated.

PMID- 29577414
TI  - Molecular insight into targeting the NK cell immune response to cancer.
AB  - Natural Killer (NK) cells have long been considered an important part of the anti
      tumor immune response due to their potent cytolytic and cytokine-secreting
      abilities. To date, a clear demonstration of the role NK cells play in human
      cancer is lacking, and there are still very few examples of therapies that
      efficiently exploit or enhance the spontaneous ability of NK cells to destroy the
      autologous cancer cells. Given the paradigm shift toward cancer immunotherapy
      over the past decade, there is a renewed push to understand how NK cell
      homeostasis and function are regulated in order to therapeutically harness these
      cells to treat cancer. This review will highlight recent advancements in our
      understanding of how growth factors impact on NK cell development,
      differentiation, survival and function with an emphasis on how these pathways may
      influence NK cell activity in the tumor microenvironment and control of cancer
      metastasis.

PMID- 29577416
TI  - Retrospective study of paracetamol poisoning in children aged zero to six years
      found no cases of liver injury.
AB  - AIM: This study focused on children aged zero to six years with suspected single
      dose paracetamol poisoning, which has not been investigated in Denmark. We
      evaluated the incidence of liver injuries and the use of activated charcoal and N
      acetylcysteine treatment. METHODS: Our retrospective study was performed in three
      paediatric hospital centres from 2001 to 2012. Data on symptoms, time of
      ingestion, blood biochemistry, treatment and adverse reactions were collected.
      The results were evaluated against the Rumack-Matthew nomogram. RESULTS: We
      identified 221 children (58% male), with a mean age of 2.67 +/- 1.05 years.
      Activated charcoal treatment was given in 87% of cases, but only 15% of the
      children received treatment within one hour of the suspected paracetamol
      poisoning. Although 80% of the children received N-acetylcysteine treatment, only
      one case (0.5%) had a toxic plasma paracetamol level according to the treatment
      nomogram. Abdominal pain or vomiting was associated with higher paracetamol
      levels in plasma. None of the children developed liver injuries. CONCLUSION: We
      found a low incidence of significant poisoning and liberal use of N
      acetylcysteine and activated charcoal treatment in Danish children aged zero to
      six years with suspected paracetamol poisoning. Vomiting or abdominal pain was
      associated with elevated plasma paracetamol levels. No liver injuries were
      reported.

PMID- 29577417
TI  - Antibiotics in the first week of life were associated with atopic asthma at 12
      years of age.
AB  - AIM: This study explored the prevalence of atopic and nonatopic asthma in 12-year
      old children and whether they were associated with different risk factors. In
      particular, we wanted to analyse whether receiving antibiotics during the first
      week of life was associated with asthma at that age. METHODS: Data were obtained
      from a longitudinal cohort study of 5654 Swedish children born in 2003. The
      parents answered questionnaires from the age of six months until 12 years. The
      response rate at 12 years was 3637/4777 (76%). RESULTS: At 12 years, 6.4%
      reported current doctor-diagnosed asthma. Treatment with antibiotics during the
      first week of life was associated with an increased risk of atopic asthma, with
      an adjusted odds ratio of 2.2 and 95% confidence interval of 1.2-4.2. Being born
      small for gestational age was associated with an increased risk of nonatopic
      asthma, with an adjusted odds ratio of 3.8 and 95% confidence interval of 1.1
      13.7. Asthma that only occurred with colds was reported by 28%. CONCLUSION:
      Antibiotic treatment during the first week of life was associated with an
      increased risk of atopic asthma at 12 years, suggesting an immune-mediated
      effect. Being born small for gestational age increased the risk of nonatopic
      asthma.

PMID- 29577418
TI  - Methadone-Not a magic bullet in melanoma therapy.
AB  - Methadone (Met) mainly acts as a MU-opioid receptor agonist. Recent evidence
      pointing towards the role of Met in sensitization of certain cancer cell lines to
      chemotherapeutic agents has promoted the hypothesis that Met may be a useful
      adjuvant to cancer chemotherapy. We wanted to address whether Met has, alone or
      in combination with a chemotherapeutic agent, an effect on melanoma cell
      viability in vitro. Only a small fraction (4.3%) of our 102 melanoma biobank cell
      lines with RNA-sequencing data showed expression of the main receptor for Met
      (OPRM1). We assessed the viability of melanoma cell lines with high, medium or
      low/no OPRM1 expression (OPRM1high , OPRM1med , OPRM1neg ) 72 hours after
      treatment with Met alone or combined with cisplatin (Cis). Our analyses show that
      Met alone did not affect cell viability. While Cis/Met treatment did not have an
      effect on viability of OPRM1med or OPRM1neg cell lines, it resulted in a slightly
      decreased cell viability of OPRM1high cells. Clinically, concurrent
      temozolomide/Met treatment did not have an effect in our single-case report of a
      patient suffering from uveal melanoma. Taken together, our findings do not
      provide evidence for recommending Met as an adjuvant to chemotherapy in patients
      with melanoma.

PMID- 29577419
TI  - An optimized FAIRE procedure for low cell numbers in yeast.
AB  - We report an optimized low-input FAIRE-seq (Formaldehyde-Assisted Isolation of
      Regulatory Elements-sequencing) procedure to assay chromatin accessibility from
      limited amounts of yeast cells. We demonstrate that the method performs well on
      as little as 4 mg of cells scraped directly from a few colonies. Sensitivity,
      specificity and reproducibility of the scaled-down method are comparable with
      those of regular, higher input amounts, and allow the use of 100-fold fewer cells
      than existing procedures. The method enables epigenetic analysis of chromatin
      structure without the need for cell multiplication of exponentially growing cells
      in liquid culture, thus opening the possibility of studying colony cell
      subpopulations, or those that can be isolated directly from environmental
      samples.

PMID- 29577420
TI  - Infarction of the septomarginal band and tricuspid papillary muscle rupture
      related to alcohol septal ablation for hypertrophic cardiomyopathy.
AB  - We presented a 77-year-old man with hypertrophic obstructive cardiomyopathy
      applied with flail tricuspid leaflet and severe tricuspid regurgitation leading
      to right heart failure 2 months after the failed septal ablation. The ruptured
      anterior tricuspid papillary muscle resulted from infarction of the base of
      anterior papillary muscle of the right ventricle (RV) confirmed by magnetic
      resonance imaging. As the septomarginal band is frequently lit up by
      intracoronary contrast that particular attention should be paid to the RV
      papillary muscles. And, if the papillary muscles or the RV free wall is
      brightened, then the use of that septal artery should be avoided.

PMID- 29577421
TI  - Direct laryngoscopy and the "Pythagorean Theorem": Is this the future? The
      importance of the elaticity of muscles of mouth's floor to obtain the hypotenuse
      of bucco-laryngeal axis.

PMID- 29577422
TI  - NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the
      Chinese population: A case-control study.
AB  - BACKGROUND: The incidence of dilated cardiomyopathy (DCM) has increased in recent
      years, and many studies have sought to further improve the general understanding
      of this condition. Previous studies have demonstrated that some single nucleotide
      polymorphisms (SNPs) associated with systemic lupus erythematosus also affect
      susceptibility to DCM, suggesting that immune-related diseases may share similar
      genetic susceptibility. Recent large-scale and genome-wide association studies
      have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as
      genetic risk factors associated with cardiac manifestations of neonatal lupus.
      Here, we aimed to determine whether these SNPs conferred susceptibility to DCM in
      the Chinese Han population. METHODS: We investigated the relationship between
      these polymorphisms and DCM risk in 273 patients with DCM and 548 healthy
      controls. Genotyping was performed using MassArray iPLEX system. RESULTS:
      Logistic regression analysis indicated that the T allele of rs3134942 in NOTCH4
      gene increased the risk of DCM by 61% compared with the G allele (Pa  = 6.57 * 10
      3 ). The SNP rs3134942 was also significantly associated with increased DCM risk
      in the additive (Pa  = 6.57 * 10-3 ) and dominant models (Pa  = 1.01 * 10-2 ).
      Additionally, rs2472299 in CYP1A2 gene showed suggestive association with reduced
      risk of DCM in the dominant model (Pa  = 4.24 * 10-2 ) and was correlated with
      smoking status in patients with DCM (Pa  = 1.56 * 10-2 ). CONCLUSIONS: Our
      findings suggested that rs3134942 in NOTCH4 may be involved in DCM risk. Further,
      studies in larger and ethnically diverse populations are required to confirm the
      results reported in this study.

PMID- 29577423
TI  - Intraoperative evaluation of perfusion in free flap surgery: A systematic review
      and meta-analysis.
AB  - BACKGROUND: Free flap survival relies on adequate tissue perfusion. We aim to
      give an overview of the available literature of all objective methods to
      intraoperatively assess free flap tissue perfusion, and the effects on (partial)
      flap loss. METHODS: A systematic review and meta-analysis according to the PRISMA
      guidelines was performed (PubMed, Cochrane Library, Embase) regarding English
      language articles. Meta-analyses were performed by pooling means and slopes using
      random-effect models. RESULTS: Sixty-four articles were included reporting on
      2369 procedures in 2009 patients with various indications. Reported methods were
      fluorescence imaging (FI), laser Doppler, oxygen saturation, ultrasound,
      (dynamic) infrared thermography, venous pressure, and microdialysis.
      Intraoperative tissue perfusion was adequately measured by the use of FI and
      laser Doppler, leading to surgical intervention or altered flap design, and
      increased flap survival. Meta-analysis showed a mean time until onset of the dye
      to become visible of 18.4 (7.27; 29.46, Q P < 0.001) sec. The relative intensity
      of the flap compared to the intensity curve of normal tissue was 75.92% (65.85;
      85.98, Q P = 0.719). The mean difference in the slope value of the oxygen
      tensions before and after the anastomosis was -0.09 (-0.12; -0;06 Q P = 0.982).
      No convincing evidence was found for the use of other methods. CONCLUSIONS: Based
      on the current literature, FI and laser Doppler are most suitable to
      intraoperatively measure free flap tissue perfusion, resulting in improved flap
      survival. However, this review was limited by the available literature.
      Additional studies are necessary to investigate the predictive value of
      intraoperative perfusion measurement.

PMID- 29577425
TI  - Quadriceps weakness preferentially predicts detrimental gait compensations among
      common impairments after total knee arthroplasty.
AB  - Patients with total knee arthroplasty (TKA) have large deficits in physical
      performance in comparison to their healthy age-matched peers. Limb asymmetry
      stemming from less relative load borne by the surgical limb during daily mobility
      is associated with diminished performance and worsens with greater mobility
      demands. How common targets of postoperative care, such as muscle weakness, lower
      limb extension power, residual knee pain, and poor balance confidence can
      influence asymmetrical limb loading remains unclear. Forty-six patients with
      unilateral TKA underwent testing of impairments and motion analysis during 10
      degrees  decline walking at 3 and 6 months postoperatively. At 3 months, only
      quadriceps femoris strength asymmetry was found to be significantly related to
      both total support moment (MT ) (beta = 0.431; p < 0.001) and knee extensor
      moment (MK ) (beta = 0.493; p < 0.001) asymmetry. Again at 6 months, only
      quadriceps strength asymmetry was related to MT (beta = 0.432; p < 0.001) and MK
      (beta = 0.534; p < 0.001) asymmetry. Quadriceps strength significantly improved
      over time in both limbs, however, deficits between limbs remained. Persistent
      quadriceps weakness is a key factor associated with walking compensation patterns
      that are limiting the capacity for greater physical performance of patients with
      TKA. The pronounced asymmetry in limb and knee loading at 3 months remains
      unchanged until at least 6 months after surgery, and its association with
      quadriceps strength asymmetry does not substantially change over time. While
      other factors may also prompt gait compensations, emphasis on improved quadriceps
      strength should be a focus of efforts to resolve gait compensations and enhance
      physical performance outcomes. (c) 2018 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:2355-2363, 2018.

PMID- 29577424
TI  - The first 142 amino acids of glutamate decarboxylase do not contribute to
      epitopes recognized by autoantibodies associated with Type 1 diabetes.
AB  - AIMS: Glutamate decarboxylase (GAD) antibodies are the most widely used
      predictive marker for Type 1 diabetes, but many individuals currently found to be
      GAD antibody-positive are unlikely to develop diabetes. We have shown previously
      that radioimmunoassays using N-terminally truncated 35 S-GAD65 (96-585) offer
      better disease specificity with similar sensitivity to full-length 35 S-GAD65 (1
      585). To determine whether assay performance could be improved further, we
      evaluated a more radically truncated 35 S-GAD65 (143-585) radiolabel. METHODS:
      Samples from people with recent-onset Type 1 diabetes (n = 157) and their first
      degree relatives (n = 745) from the Bart's-Oxford family study of childhood
      diabetes were measured for GAD antibodies using 35 S-labelled GAD65 (143-585).
      These were screened previously using a local radioimmunoassay with 35 S-GAD65 (1
      585). A subset was also tested by enzyme-linked immunosorbent assay (ELISA),
      which performs well in international workshops, but requires 10 times more serum.
      Results were compared with GAD antibody measurements using 35 S-GAD65 (1-585) and
      35 S-GAD65 (96-585). RESULTS: Sensitivity of GAD antibody measurement was
      maintained using 35 S-GAD65 (143-585) compared with 35 S-GAD65 (1-585) and 35 S
      GAD65 (96-585). Specificity for Type 1 diabetes was improved compared with 35 S
      GAD65 (1-585), but was similar to 35 S-GAD65 (96-585). Relatives found to be GAD
      antibody-positive using these truncated labels were at increased risk of diabetes
      progression within 15 years, compared with those positive for GAD(1-585) antibody
      only, and at similar risk to those found GAD antibody-positive by ELISA.
      CONCLUSIONS: The first 142 amino acids of GAD65 do not contribute to epitopes
      recognized by Type 1 diabetes-associated GAD antibodies. Low-volume
      radioimmunoassays using N-terminally truncated 35 S-GAD65 are more specific than
      those using full-length GAD65 and offer practical alternatives to the GAD
      antibody ELISA for identifying children at increased risk of Type 1 diabetes.

PMID- 29577426
TI  - Significant association between RGS14 rs12654812 and nephrolithiasis risk among
      Guangxi population in China.
AB  - BACKGROUND: Nephrolithiasis is a worldwide health problem that affects almost all
      populations. This study aimed to evaluate the association between rs12654812 of
      regulator of G protein signaling 14 (RGS14) gene and nephrolithiasis in the
      Chinese population. METHODS: A total of 1541 participators including 830 cases
      and 711 controls were included from Guangxi area in China. Age, sex, BMI, smoking
      status, drinking status, creatinine, uric acid, and urea nitrogen were analyzed
      between the case group and control group. RESULTS: We found that the G/A+A/A
      genotypes of rs12654812 had a significantly increased nephrolithiasis risk after
      adjusting age, sex, BMI, smoking, drinking, and hypertension, compared with G/G
      genotype (OR = 1.361, 95% CI = 1.033-1.794, P = .029). This hazardous effect was
      more pronounced in subgroup of age < 50, ever smoking, ever drinking, creatinine
      normal, and high uric acid. The G/A genotype of rs12654812 also had a
      significantly increased nephrolithiasis risk compared with G/G genotype. The A
      allele of rs12654812 significantly increased the risk of nephrolithiasis compared
      with the G allele after adjusting for age, sex, BMI, smoking, drinking and
      hypertension (OR = 1.277, 95% CI = 1.013-1.609, P = .038). CONCLUSIONS: Our
      results suggest that the RGS14 polymorphism is involved in the etiology of
      nephrolithiasis and thus may be a genetic marker for nephrolithiasis.

PMID- 29577427
TI  - An unusual "mass" within the left atrium: Localized aneurysm of a patent foramen
      ovale tunnel.
AB  - Masses on the interatrial septum are usually caused by myxomas or thrombi within
      a patent foramen ovale. We report a 53-year-old male patient with a hollow mass
      within the left atrium that was incidentally found during a routine transthoracic
      echocardiography. Further investigation of the mass with transesophageal two- and
      three-dimensional echocardiography has revealed that the mass was a localized
      aneurysm of a patent foramen ovale tunnel. While aneurysms of interatrial septum
      are relatively common in normal population, to the best of our knowledge, present
      case is the first report of a localized aneursym of a patent foramen ovale
      tunnel.

PMID- 29577428
TI  - Decompression of the anterior thoracic spinal canal using a novel full-endoscopic
      uniportal transthoracic retropleural technique-an anatomical feasibility study in
      human cadavers.
AB  - Surgery for thoracic disc herniation and spinal stenosis is comparatively rare
      and often demanding. The goal is to achieve sufficient decompression without
      manipulating the spinal cord. Individual planning and various surgical techniques
      and approaches are required. This anatomical study examines the feasibility of a
      novel full-endoscopic uniportal technique with a transthoracic retropleural
      approach for decompression of the anterior thoracic spinal canal. Operations were
      performed on three fresh adult cadavers. The endoscope used, from RIWOspine,
      Germany, has a shaft cross-section of 6.9 * 5.9 mm and a 25 degrees  view angle.
      It contains an eccentric intraendoscopic working channel with a diameter of 4.1
      mm. A transthoracic retropleural approach was used. The anatomical structures
      were dissected and the anterior thoracic epidural space was decompressed. The
      planned steps of the operation were performed on all cadavers. The transthoracic
      retropleural approach allowed the target region to be accessed easily. The
      anatomical structures could be identified and dissected. The anterior thoracic
      epidural space could be decompressed sufficiently. Using the uniportal full
      endoscopic operation technique with a transthoracic retropleural approach, the
      anterior thoracic epidural space can be adequately reached. This is a minimally
      invasive method with the known advantages of an endoscopic technique under
      continuous irrigation. The retropleural approach allows direct access. The
      instruments are available for clinical use and have been established for years in
      other operations on the entire spine. Clin. Anat. 31:716-723, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29577429
TI  - Echocardiographic advances in hypertrophic cardiomyopathy: Three-dimensional and
      strain imaging echocardiography.
AB  - In the recent past, new ultrasound technologies, such as three-dimensional
      echocardiography and strain imaging echocardiography, raised up in clinical
      practice leading to a better assessment of cardiac morphology and performance.
      These tools may assess regional cardiac mechanics, detecting clinical and
      subclinical myocardial dysfunction in different settings such as ischemic heart
      disease, cardiomyopathies, and heart valve diseases. Interesting results derive
      from patients affected from hypertrophic cardiomyopathy (HCM). Particularly, the
      mentioned techniques are progressively redefining the role of echocardiography in
      diagnostic evaluation of HCM variants such as apical HCM, detection of the
      underlying conditions of increased wall thickness, assessment of subclinical
      myocardial impairment, and potentially refine risk stratification and prognosis.
      In this review, we describe the clinical uses of these methodologies and the
      perspective application in HCM patients.

PMID- 29577430
TI  - Extremophilic yeasts: the toughest yeasts around?
AB  - Microorganisms are widely distributed in a multitude of environments including
      ecosystems that show challenging features to most life forms. The combination of
      extreme physical and chemical factors contributes to the definition of extreme
      habitats although the definition of extreme environments changes depending on
      one's point of view: anthropocentric, microbial-centric or zymo-centric.
      Microorganisms that live under conditions that cause hard survival are called
      extremophiles. In particular organisms that require extreme conditions are called
      true extremophiles while organisms that tolerate them to some extent are termed
      extremotolerant. Deviation of temperature, pH, osmotic stress, pressure and
      radiation from the common range delineates extreme environments. Yeasts are
      versatile eukaryotic organisms that are not frequently considered the toughest
      microorganisms in comparison with prokaryotes. Nevertheless extremophilic or
      extremotolerant species are present also within this group. Here a brief
      description is provided of the main extreme habitats and the metabolic and
      physiological modifications adopted by yeasts depending on their adverse
      conditions. Additionally the main extremophilic and extremotolerant yeast species
      associated with a few extreme habitats are listed.

PMID- 29577431
TI  - Is podoplanin expression associated with transforming growth factor-beta
      signaling in odontogenic cysts and tumors?
AB  - BACKGROUND: Induction of podoplanin by transforming growth factor-beta (TGF-beta)
      has been shown in a number of lesions but not in odontogenic tumors (OTs). We
      evaluated the association between these markers in OTs for the first time and
      compared their expression among the different neoplasms. METHODS:
      Immunohistochemistry using monoclonal antibody against podoplanin and TGF-beta
      was performed on 76 odontogenic cysts and tumors. Spearman's correlation
      coefficient, Kruskal-Wallis, and Mann-Whitney U tests followed by adjustment with
      Bonferroni were used for statistical analysis (P < .05). RESULTS: A significant
      difference in podoplanin expression was found among the lesions consisting of
      solid ameloblastomas, adenomatoid odontogenic tumors, ameloblastic fibromas,
      odontogenic myxomas (OMs), odontogenic keratocysts, and calcifying odontogenic
      cysts. Significant differences were observed only between OMs and each of the
      other neoplasms. Podoplanin immunostaining in the connective tissue was absent in
      most lesions. TGF-beta was significantly different among the study sample but not
      between the lesions in paired comparisons. None of the studied OTs showed
      significant correlations between podoplanin-TGF-beta, in either the epithelium or
      the stroma. These markers were also descriptively reported in calcifying
      epithelial odontogenic tumors. CONCLUSIONS: The inductive effect of TGF-beta on
      podoplanin seems to be limited, if any, in odontogenic lesions. Podoplanin
      appears to play a role in some aspects of OTs with epithelial or mixed origins.
      Despite the possible participation of podoplanin in tumorigenesis, it may not
      necessarily be involved in the aggressive behavior of OTs.

PMID- 29577432
TI  - Anatomical study of the articular branches innervated the hip and knee joint with
      reference to mechanism of referral pain in hip joint disease patients.
AB  - INTRODUCTION: Referred pain in the anterior knee joint is the most common symptom
      in hip disease patients. The development of referred pain is considered to be
      related to dichotomizing peripheral sensory fibers. However, no gross anatomical
      findings identify any dichotomizing fibers innervating both the hip and knee
      joints. We dissected the femoral and obturator nerves in human cadavers to
      investigate the distribution of the articular branches in the hip and knee
      joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five
      from females, nine from males, average age 73.8 +/- 14.1 years) were observed
      macroscopically. The articular branches of the femoral and obturator nerves were
      dissected at the anterior margin of the groin toward the thigh region. After
      dissections of the articular nerves of the hip joints, the femoral and obturator
      nerves were exposed from proximally to distally to identify the articular nerves
      of the knee joints. The branching pattern of the articular branches in the hip
      and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve
      supplied articular branches to the anteromedial aspect of both the hip and knee
      joints. These articular branches were derived from the same bundle of femoral
      nerve. These gross anatomical findings suggested that dichotomizing peripheral
      sensory fibers innervate the hip and knee joints and these could relate to the
      referred pain confirmed in the anterior knee joints of patients with hip disease.
      Clin. Anat. 31:705-709, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29577433
TI  - Variability in facial-muscle innervation: A comparative study based on
      electrostimulation and anatomical dissection.
AB  - Facial-nerve palsy is the most common complication during facial surgery.
      However, there are few detailed reports on the distribution of the terminal
      branches of the facial nerve to the mimetic muscles. This also applies to the
      communicating branches. The aim of our study was to assess the variability of
      communicant and terminal branches of the facial nerve in humans. This prospective
      study involved anatomical dissections and intraoperative electric stimulation of
      facial nerves. We first performed 30 dissections to define the branching patterns
      of the extracranial facial nerve, with particular focus on the penetrating points
      into the mimetic muscles. We then studied and compared these preliminary data
      with 14 operative facial stimulations conducted during parotidectomies. Each
      trunk and branch received systematic electrostimulation. The electrostimulation
      and facial-and-neck movements were analyzed by two independent reviewers. The
      peripheral branching and intercommunication of the facial branches were highly
      variable. Combining electrostimulation and dissections, the frontalis muscle, the
      depressor labii inferioris and the platysma showed little nerve recuperation
      whereas the sphincter muscles (orbicularis ori and oculi) were anatomically
      protected. Facial-muscle innervation differed among individuals. We found complex
      variations in the facial branching mode. Our study highlights the branches and
      corresponding areas that could be considered anatomically risky. Clin. Anat.,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29577434
TI  - Internal and external morphology of mandibular molars: An original micro-CT study
      and meta-analysis with review of implications for endodontic therapy.
AB  - The aim of this radiological micro-CT study and meta-analysis was to determine
      the morphological features of the root canal anatomy of the mandibular molars.
      The radiological study included micro-CT scans of 108 mandibular first, 120
      mandibular second, and 146 mandibular third molars. For our meta-analysis, an
      extensive search was conducted through PubMed, Embase, and Web of Science to
      identify articles eligible for inclusion. Data extracted included investigative
      method (cadaveric, intraoperative, or imaging), Vertucci type of canal
      configuration, presence/number of canals, roots, apical foramina, apical deltas,
      and intercanal communications. In the mesial roots of mandibular molars, the most
      frequent Vertucci type of canal configuration was type IV, except for the
      mandibular third molar where type I was most common. Type I was most common in
      the distal root. There were usually two canals in the mesial root and one in the
      distal root. Two was the most common number of roots, and a third root was most
      prevalent in Asia. One apical foramen was most common in the distal root and two
      apical foramina in the mesial root. Intercanal communications were most frequent
      in the mesial root. Knowledge of the complex anatomy of the mandibular molars can
      make root canal therapy more likely to succeed. We recommend the use of cone-beam
      computed tomography before and after endodontic treatment to enable the root
      anatomy to be accurately described and properly diagnosed, and treatment outcome
      to be assessed. Clin. Anat. 31:797-811, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29577435
TI  - ACU lecture: One-stage hypospadias repair - Future is Asia the East.

PMID- 29577436
TI  - Preformed donor-specific antibodies do not affect the 1-year allograft survival
      in living donor liver transplantation.
AB  - The effect of preformed donor-specific antibodies (DSAs) on liver transplantation
      (LT) remains unclear, especially in the field of living donor LT (LDLT). Herein,
      we evaluated the prevalence of preformed DSAs and their effect on graft outcome
      in LDLT in the first year following surgery. Using the Luminex(r) Single Antigen
      assay, we analyzed the preoperative sera of 61 adult LDLT recipients between 2014
      and 2015. Clinical outcomes and pathologic findings including complement
      component 4d (C4d) expression in the first year after LT were retrospectively
      reviewed. Regardless of the class of DSA, DSAs with mean fluorescence intensity
      (MFI) >=1000 were defined as positive and preformed DSA with MFI >=5000 was
      defined as strongly positive. Fifteen patients (24.6%) had preformed DSAs, and 8
      patients (13.1%) showed strongly positive preformed DSAs. Among 15 DSA positive
      patients, 2 (13.3%) showed persistent DSAs after LDLT. No de novo DSAs were noted
      in patients without preformed DSAs. Preformed DSAs were not related to graft
      dysfunction, laboratory values, or C4d expression or other pathologic findings in
      the first year of LDLT. In conclusion, preformed DSAs persisted during follow-up
      in 13.3% of cases and did not have adverse effect on histologic or clinical
      outcomes in the first year of LDLT.

PMID- 29577438
TI  - Endoscopic omental patch using an over-the-scope clip for endoscopic retrograde
      cholangiopancreatography-related large duodenal perforation.

PMID- 29577437
TI  - Oral administration of cernitin pollen extract (Cernilton(r) ) for 30 days might
      be useful to avoid unnecessary biopsy in prostate biopsy candidates: A
      preliminary study.
AB  - OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate
      specific antigen level prostate biopsy candidates, and to develop an ideal
      protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61
      patients were administrated cernitin pollen extract tablets (two tablets t.i.d.)
      for 30 days, and then underwent a prostate biopsy with >=12 systematic and
      targeted biopsy cores obtained. Serum prostate-specific antigen levels were
      examined before and after administration of the pollen extract, and the change in
      serum prostate-specific antigen and the rate of change were analyzed in relation
      to negative and positive biopsy results for cancer. RESULTS: The mean change in
      serum prostate-specific antigen and rate of change after administration of
      cernitin pollen extract in all patients were -0.6 +/- 1.4 ng/mL and -7.6 +/-
      16.1%, respectively, which were significantly different from the baseline values
      (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change
      values and rates were compared between patients negative and positive for cancer,
      a significant difference between those groups was observed (P = 0.04 and P =
      0.03, respectively). CONCLUSIONS: The present study is the first to show that an
      ideal protocol using cernitin pollen extract has the potential to avoid an
      unnecessary prostate biopsy procedure in patients with elevated prostate-specific
      antigen, possibly caused by inflammation. Additional studies with greater numbers
      of participants are required to confirm our findings and develop an ideal
      protocol.

PMID- 29577439
TI  - Glutamatergic cells in the periaqueductal gray matter mediate sensory inputs
      after bladder stimulation in freely moving rats.
AB  - OBJECTIVES: To determine the phenotype of the ventrolateral part of the
      periaqueductal gray matter neurons after bladder stimulation. METHODS: In the
      experimental group, electrical stimulation of the bladder was carried out under
      freely moving condition by a bipolar stimulation electrode implanted in the
      bladder wall. Thereafter, the brain sections were processed for
      immunohistochemical analysis using antibodies against c-Fos (neuronal activation
      marker) together with one of the following: tyrosine hydroxylase (dopaminergic
      cell marker), vesicular glutamate transporter (glutamatergic cell marker),
      serotonin, glutamate decarboxylase (glutamate decarboxylase 67, gamma
      aminobutyric acid cell marker) and neuronal nitric oxide synthase. We used design
      based confocal stereological analysis to quantify the immunohistochemically
      stained sections. RESULTS: A significant increase in the number of c-Fos-positive
      cells in the ventrolateral part of the periaqueductal gray matter after
      stimulation was found. Furthermore, the ratio of c-Fos cells double labeled with
      vesicular glutamate transporter was significantly higher in the ventrolateral
      part of the periaqueductal gray matter region in the stimulated compared with the
      sham group. Quantitative analysis of the other four cell types did not show any
      significant difference. CONCLUSION: These findings suggest that glutamatergic
      neurotransmission in the ventrolateral part of the periaqueductal gray matter is
      seemingly the main pathway to be activated after receiving sensory signals from
      the bladder.

PMID- 29577441
TI  - Editorial Comment from Dr Defidio to Thulium laser ablation facilitates
      retrograde intra-renal surgery for upper urinary tract urothelial carcinoma.

PMID- 29577440
TI  - Intensity ratio curve analysis of small renal masses on T2-weighted magnetic
      resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell
      carcinoma.
AB  - OBJECTIVES: To assess the diagnostic ability of a pixel intensity-based analysis
      in evaluating the magnetic resonance imaging characteristics of small renal
      masses, especially in differentiating fat-poor angiomyolipoma from renal cell
      carcinoma. METHODS: T2-weighted images from 121 solid small renal masses (<4 cm)
      without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell
      carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell
      carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted
      using intensity ratios, which were ratios of signal intensities of tumor pixels
      (each pixel along a linear region of interest drawn across the renal tumor on T2
      weighted image) to the signal intensity of a normal renal cortex. The diagnostic
      ability of the intensity ratio curve analysis was evaluated. RESULTS: The tumors
      were classified into three types: intensity ratio fat-poor angiomyolipoma (n =
      19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity
      ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high
      intensity and heterogeneity; and other type of intensity ratio (n = 26),
      including tumors that did not fall into the above two categories. The
      sensitivity/specificity/accuracy of the intensity ratio curve analysis in
      diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the
      intensity ratio curve analysis was applied only to the tumor with undetermined
      radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma
      compared with subjective reading alone significantly improved (93% vs 50%; P =
      0.014). CONCLUSIONS: Our novel semiquantitative model for combined assessment of
      key features of fat-poor angiomyolipoma, including low intensity, homogeneity and
      absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor
      angiomyolipoma more accurate.

PMID- 29577442
TI  - Diet and risk of myopia in three-year-old Singapore children: the GUSTO cohort.
AB  - BACKGROUND: To investigate the relationship between dietary intakes at six, nine
      and 12 months and risk of myopia in three-year-old children in a birth cohort.
      METHODS: Three hundred and seventeen children from the Growing Up in Singapore
      Towards Healthy Outcomes (GUSTO) study were included. Dietary intake at six, nine
      and 12 months of age was ascertained using either 24-hour recalls or three-day
      food diaries completed by parents. Cycloplegia was achieved with three drops of
      one per cent cycloplentolate instilled at five minute intervals. Cycloplegic
      autorefraction and axial length (AL) were measured at three years of age with a
      table-mounted autorefractor and optical biometer, respectively. Myopia was
      defined as spherical equivalent (SE) of <= -0.50 D. Associations of dietary
      intake with SE, AL and myopia were examined by single dietary factor models using
      two multivariable regression models. Model 1 included adjusting for age, gender
      and total energy intake. Model 2 included additional adjustments for ethnicity,
      time spent outdoors, maternal education and parental myopia. RESULTS: In the
      single dietary factor adjusted models, dietary intakes at six, nine and 12 months
      were not associated with SE, AL and myopia. In model 1, protein, fat and
      carbohydrate intakes were not associated with SE, AL and myopia at any of the
      three time points (p > 0.05). In model 2, protein, fat and carbohydrate intakes
      were not associated with SE, AL and myopia at any of the three time points (p >
      0.05). CONCLUSIONS: In this study, there was no evidence that diet at ages six,
      nine and 12 months was related to SE, AL or myopia at age three years. Further
      prospective studies with larger sample sizes are needed to understand the
      influence of diet on eye development in young children.

PMID- 29577443
TI  - A new era for translational atopic dermatitis research and management.

PMID- 29577445
TI  - Should the Japanese government support travels for transplantation as a policy
      under the National Health Insurance system?

PMID- 29577444
TI  - Single-Molecule Sensing with Nanopore Confinement: From Chemical Reactions to
      Biological Interactions.
AB  - The nanopore can generate an electrochemical confinement for single-molecule
      sensing that help understand the fundamental chemical principle in nanoscale
      dimensions. By observing the generated ionic current, individual bond-making and
      bond-breaking steps, single biomolecule dynamic conformational changes and
      electron transfer processes that occur within pore can be monitored with high
      temporal and current resolution. These single-molecule studies in nanopore
      confinement are revealing information about the fundamental chemical and
      biological processes that cannot be extracted from ensemble measurements. In this
      Concept article, we introduce and discuss the electrochemical confinement effects
      on single-molecule covalent reactions, conformational dynamics of individual
      molecules and host-guest interactions in protein nanopores. Then, we extend the
      concept of nanopore confinement effects to confine electrochemical redox
      reactions in solid-state nanopores for developing new sensing mechanisms.

PMID- 29577446
TI  - The anatomy of the male inferior hypogastric plexus: What should we know for
      nerve sparing surgery.
AB  - The aim of this study was to investigate the nerve supply to the structures in
      the male lesser pelvis and review its clinical relevance, especially during nerve
      sparing surgery. Three formalin-embalmed and 16 Thiel-embalmed male hemipelves
      were used. They were microdissected after repeated treatments with nitric acid
      diluted 1:10 with milliQ-water. The inferior hypogastric plexus (IHP) is a fan
      like structure lateral from the rectum on the fascia of the levator ani. Nerves
      emerging from the proximal, solid part of the plexus follow the internal iliacal
      vessels and reach the prostate from dorsolateral. The innervation of the urethra
      and the corpora cavernosa derives from two origins: one follows the ejaculatory
      duct and the seminal vesicle, reaching the proximal urethra and the prostate from
      dorsal; the other follows the inferior vesical artery to reach the prostate from
      lateral, and then forms the neurovascular bundle on both sides of the prostatic
      fascia, spreading to the pelvic floor muscles and the corpora cavernosa along
      with the distal urethra. A connection between the two parts was demonstrated in
      approximately one third of the samples investigated. The nerve supply to the
      urinary bladder, the urethra, and the corpora cavernosa emerges mainly from the
      IHP. The innervation of the proximal urethra and its autonomic muscular
      structures has a dorsal (ejaculatory duct) and lateral (inferior vesical artery)
      origin. To maintain good erectile and continence function it is important to save
      both the dorsal and lateral neurovascular roots. Clin. Anat. 31:788-796, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29577447
TI  - High terbinafine resistance in Trichophyton interdigitale isolates in Delhi,
      India harbouring mutations in the squalene epoxidase gene.
AB  - In the last few years, infections caused by dermatophytes along with a
      concomitant increase in the number of difficult to treat cases have increasingly
      been recognised, indicating that dermatophytosis remains a challenging public
      health problem. The majority of infections are caused by Trichophyton rubrum and
      Trichophyton mentagrophytes complex. Terbinafine, an allylamine antifungal used
      orally and topically is considered to be a first-line drug in the therapy of
      dermatophyte infections. Terbinafine resistance has been predominately attributed
      to point mutations in the squalene epoxidase (SQLE) target gene a key enzyme in
      the ergosterol biosynthetic pathway leading to single amino acid substitutions.
      Here, we report the largest series of 20 terbinafine-resistant Trichophyton
      interdigitale isolates obtained predominately from cases of tinea corporis/cruris
      in three hospitals in Delhi, India exhibiting elevated MICs (4 to >=32 MUg/mL) to
      terbinafine and all harbouring single-point mutations Leu393Phe or Phe397Leu in
      the SQLE gene. In 12 (60%) T. interdigitale isolates, the Phe397Leu substitution
      was observed, whereas in the remaining 8 (40%) isolates the substitution
      Leu393Phe was reported for the first time in T. interdigitale. Furthermore, 10
      susceptible T. interdigitale isolates (0.125-2 MUg/mL) had a wild-type genotype.
      Remarkably, considerably high terbinafine resistance rate of 32% was observed
      among 63 T. interdigitale isolates identified by sequencing of the internal
      transcribed spacer region. This high level of terbinafine resistance of Indian
      dermatophyte isolates is worrisome warranting antifungal susceptibility testing
      and mutation analysis for monitoring this emerging resistance.

PMID- 29577448
TI  - Surgical approach, cost, and complications of appendectomy in kidney transplant
      recipients.
AB  - Kidney transplant recipients (KTRs) have greater morbidity and length of stay
      (LOS) following certain surgical procedures than non-KTR. Given that appendectomy
      is one of the most common surgical procedures, we investigated differences in
      outcomes between 1336 KTR and 2 640 247 non-KTR postappendectomy at transplant
      and nontransplant centers in the United States from 2000 to 2011, using NIS data
      and adjusting for patient-level and hospital-level factors. Postoperative
      complications were identified using ICD-9 codes. Among KTR, there were no post
      appendectomy in-hospital deaths, compared to a 0.2% in non-KTR (P = .5). Overall
      complications were similar among KTR and non-KTR (17.0% vs 11.6%; aOR:0.77
      1.121.61 ). LOS and costs were greater for KTR compared to non-KTR (LOS ratio
      1.19 1.311.45 ; cost ratio 1.11 1.171.26 ). Only 44.8% of KTR had laparoscopic
      approach compared to 54.5% of non-KTR, but had similar complication rates (10.6
      vs 8.7%, P = .5). When treated at transplant centers, KTR had similar
      complications (aOR 0.44 0.791.43 ), but longer LOS (ratio 1.21 1.371.55 ) and
      greater hospital-associated costs (ratio 1.19 1.291.41 ) than non-KTR.
      Conversely, at nontransplant centers, KTR and non-KTR had similar complications
      (aOR 0.75 1.232.0 ), LOS (ratio 0.84 0.961.09 ), and cost (ratio 0.93 1.011.10 ).
      Contrary to other procedures, KTR did not constitute a high-risk group for
      patients undergoing appendectomy.

PMID- 29577449
TI  - No apparent benefit of preemptive sorafenib therapy in liver transplant
      recipients with advanced hepatocellular carcinoma on explant.
AB  - BACKGROUND: Sorafenib has shown survival benefits in patients with advanced HCC;
      however, limited data are available on its role in OLT recipients with advanced
      HCC in the explant. AIM: Evaluate the role of preemptive sorafenib therapy on HCC
      recurrence and survival after OLT with advanced HCC on explant pathology.
      METHODS: We retrospectively reviewed the outcome after OLT of all HCC recipients
      with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on
      preemptive treatment with sorafenib. RESULTS: During the observation period, 217
      HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion
      of 5 patients who were lost to follow-up, 45 LT recipients were finally included
      for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib
      Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival
      were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally,
      sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74,
      95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P
      = .84) on multivariate Cox proportional hazard model with sorafenib use as time
      varying covariates. CONCLUSION: Preemptive treatment with sorafenib in OLT
      recipients with high-risk features in explant does not improve HCC recurrence
      free or overall survival.

PMID- 29577450
TI  - Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder in DSM-5
      and ICD-11: Clinical and Behavioral Correlates.
AB  - The American Psychiatric Association and the World Health Organization provide
      distinct trauma-based diagnoses in the fifth edition of the Diagnostic and
      Statistical Manual (DSM-5), and the forthcoming 11th version of the International
      Classification of Diseases (ICD-11), respectively. The DSM-5 conceptualizes
      posttraumatic stress disorder (PTSD) as a single, broad diagnosis, whereas the
      ICD-11 proposes two "sibling" disorders: PTSD and complex PTSD (CPTSD). The
      objectives of the current study were to: (a) compare prevalence rates of
      PTSD/CPTSD based on each diagnostic system; (b) identify clinical and behavioral
      variables that distinguish ICD-11 CPTSD and PTSD diagnoses; and (c) examine the
      diagnostic associations for ICD-11 CPTSD and DSM-5 PTSD. Participants in a
      predominately female clinical sample (N = 106) completed self-report scales to
      measure ICD-11 PTSD and CPTSD, DSM-5 PTSD, and depression, anxiety, borderline
      personality disorder, dissociation, destructive behaviors, and suicidal ideation
      and self-harm. Significantly more people were diagnosed with PTSD according to
      the DSM-5 criteria (90.4%) compared to those diagnosed with PTSD and CPTSD
      according to the ICD-11 guidelines (79.8%). An ICD-11 CPTSD diagnosis was
      distinguished from an ICD-11 PTSD diagnosis by higher levels of dissociation (d =
      1.01), depression (d = 0.63), and borderline personality disorder (d = 0.55).
      Diagnostic associations with depression, anxiety, and suicidal ideation and self
      harm were higher for ICD-11 CPTSD compared to DSM-5 PTSD (by 10.7%, 4.0%, and
      7.0%, respectively). These results have implications for differential diagnosis
      and for the development of targeted treatments for CPTSD.

PMID- 29577451
TI  - Positive Jacquet's sign in traction alopecia.

PMID- 29577452
TI  - The Concept of "Noble, Heteroatom-Doped Carbons," Their Directed Synthesis by
      Electronic Band Control of Carbonization, and Applications in Catalysis and
      Energy Materials.
AB  - Carbonization of organic compounds with a highest occupied molecular orbital
      (HOMO) level more positive than 1.3 V practically automatically results in highly
      sp2 -conjugated, heteroatom-doped carbons. Due to the stability of the starting
      compounds, carbon bond formation is restricted to result in morphologies with a
      surprisingly high local order which as such are noble, i.e., they are hard to
      oxidize and combust. The work function of electrons in these systems is so
      positive that the systems usually accept electrons, i.e., they oxidize other
      matter rather than being oxidized. Such noble, heteroatom-doped carbons have been
      proven to be efficient, metal-free electrocatalysts, but can be also beneficially
      used in the manufacturing of carbon nanomaterials for energy applications or as
      highly active, non-innocent catalytic supports.

PMID- 29577453
TI  - Highly Elastic and Ultratough Hybrid Ionic-Covalent Hydrogels with Tunable
      Structures and Mechanics.
AB  - Hybrid ionically-covalently crosslinked double-network (DN) hydrogels are
      attracting increasing attention on account of their self-recovery ability and
      fatigue resistance, but their relative low mechanical strength and tedious
      performance adjustment severely limit their applications. Herein, a new strategy
      to concurrently fabricate hybrid ionic-covalent DN hydrogels and modulate their
      structures and mechanics is reported, in which an in situ formed chitosan ionic
      network is incorporated by post-crosslinking the chitosan-based composite
      hydrogel using multivalent anions solutions. The obtained hybrid DN hydrogels
      exhibit predominant mechanical properties including superior elastic modulus,
      high tensile strength, and ultrahigh fracture energy because of the more
      efficient energy dissipation of rigid short-chain chitosan network. Notably, the
      swollen hydrogels still remain mechanically strong and tough even after immersion
      in water for 24 h. More significantly, simply changing the post-crosslinking time
      can vary the compactness and rigidity of the chitosan network in situ, achieving
      flexible and efficient modulation of the structures and mechanics of the hybrid
      DN hydrogels. This study opens up a new horizon in the preparation and regulation
      of DN hydrogels for promising applications in tissue scaffolds, actuators, and
      wearable devices.

PMID- 29577454
TI  - Tumor necrosis factor receptor-associated factor 6 mediated the promotion of
      salivary adenoid cystic carcinoma progression through Smad-p38-JNK signaling
      pathway induced by TGF-beta.
AB  - BACKGROUND: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has
      been proved to play an important role in tumorigenesis, invasion, and metastasis.
      However, its precise role salivary adenoid cystic carcinoma (SACC) has not been
      determined. The aim of this study was to explore the role of TRAF6 in SACC
      including invasion and metastasis of SACC cells. MATERIALS AND METHODS:
      Immunohistochemistry and quantitative real-time PCR were performed in SACC
      tissues paired with their adjacent normal tissues to analyze the expression of
      TRAF6. Downstream proteins expression was explored when TRAF6 was knockdown by
      siRNA. RESULTS: The results show that TRAF6 is upregulated in SACC samples,
      especially in SACC with metastasis, which is closely correlated with an
      aggressive phenotype (P = .0073) and shorter life survival span (P = .0061) in
      SACC patients. Knockdown of TRAF6 can attenuate the promotion effect of SACC cell
      invasion induced by TGF-beta. Western blot results also showed that silencing
      TRAF6 expression can inhibit the activation of SMAD2, SMAD3, ERK, p38, and JNK
      induced by TGF-beta in SACC cells. CONCLUSION: These data suggested that TRAF6
      regulates TGF-beta-mediated SACC progression through SMAD2/3-ERK-p38-JNK
      cascades.

PMID- 29577456
TI  - Revisiting the Role of Polysulfides in Lithium-Sulfur Batteries.
AB  - Intermediate polysulfides (Sn , where n = 2-8) play a critical role in both
      mechanistic understanding and performance improvement of lithium-sulfur
      batteries. The rational management of polysulfides is of profound significance
      for high-efficiency sulfur electrochemistry. Here, the key roles of polysulfides
      are discussed, with regard to their status, behavior, and their
      correspondingimpact on the lithium-sulfur system. Two schools of thoughts for
      polysulfide management are proposed, their advantages and disadvantages are
      compared, and future developments are discussed.

PMID- 29577455
TI  - Diminished impact of cytomegalovirus infection on graft vasculopathy development
      in the antiviral prophylaxis era - a retrospective study.
AB  - Evidence concerning an association between cytomegalovirus (CMV) infection and
      accelerated cardiac allograft vasculopathy (CAV) is inconclusive. Data were
      analyzed retrospectively from 297 consecutive heart transplants between 1.1.2002
      and 31.12.2012. Patients <=18 years of age, survival, and follow-up <=1-year post
      transplant and patients with early CAV were excluded. CMV-infection was diagnosed
      and monitored closely in the first year. CAV was diagnosed by coronary
      angiography via left heart catheterization, and results were categorized
      according to the International Society of Heart and Lung Transplantation (ISHLT)
      scoring system. Risk factors for CAV were tested in a multivariable model. Median
      follow-up was 7.5 years (IQR: 5.6-10.3). CMV infection in the first year after
      transplantation occurred in 26% of patients (n = 78), CMV disease in 5% (n = 15).
      CAV >=1 ISHLT was detected in 36% (n = 108). Incidence of CAV >1 ISHLT and
      severity of CAV increased over time. No statistically significant association
      between CMV infection and disease within the first year and risk of CAV after 1
      year post-HTx was detected in the univariate (P = 0.16) and multivariable [hazard
      ratio (HR), 1.36; confidence interval (CI), 0.89-2.07; P = 0.16] Cox regression.
      In the multivariable Cox regression, donor age (HR, 1.04; 95% CI, 1.02-1.06; P <
      0.01) and acute cellular rejection (ACR) >=2R in the first year after HTx (HR,
      1.77; 95% CI, 1.06-2.95; P = 0.03) were independent risk factors for CAV
      development. In our cohort, CMV infection and disease in the first year after
      transplantation did not significantly influence the risk of CAV in the long-term
      follow-up.

PMID- 29577457
TI  - Traceable Nanoparticles with Dual Targeting and ROS Response for RNAi-Based
      Immunochemotherapy of Intracranial Glioblastoma Treatment.
AB  - The chemotherapy of glioblastoma is severely hindered by the immunosuppressive
      tumor microenvironment, especially the tumor growth factor beta (TGF-beta), an
      immunosuppressive cytokine. In this study, it is proposed to employ RNAi-based
      immunomodulation to modify the tumor immune microenvironment and improve the
      effect of chemotherapy. Herein, a nanotheranostic system (Angiopep
      LipoPCB(Temozolomide+BAP/siTGF-beta), ALBTA) with dual targeting and ROS response
      is established for intracranial glioblastoma treatment. The traceable
      nanoparticles exhibit strong siRNA condensation, high drug loading efficiency,
      good serum stability, and magnetic property. They can efficiently cross the blood
      brain barrier and target to glioblastoma cells via receptor-mediated
      transcytosis. The zwitterionic lipid (distearoyl phosphoethanol-amine
      polycarboxybetaine lipid) in ALBTA promotes endosomal/lysosomal escape, and thus
      enhances the cytotoxicity of temozolomide and improves gene silencing efficiency
      of siTGF-beta. ALBTA significantly improves the immunosuppressive
      microenvironment and prolongs the survival time of glioma-bearing mice. Moreover,
      ALBTA can be accurately traced by MRI in brain tumors. The study indicates that
      this immunochemotherapeutic platform can serve as a flexible and powerful
      synergistic system for treatment with brain tumors as well as other brain
      diseases in central nervous system.

PMID- 29577458
TI  - Near-Infrared-Light-Activatable Nanomaterial-Mediated Phototheranostic
      Nanomedicines: An Emerging Paradigm for Cancer Treatment.
AB  - Cancer is one of the most deadly diseases threatening the lives of humans.
      Although many treatment methods have been developed to tackle cancer, each
      modality of cancer treatment has its own limitations and drawbacks. The
      development of minimally invasive treatment modalities for cancers remains a
      great challenge. Near-infrared (NIR) light-activated nanomaterial-mediated
      phototherapies, including photothermal and photodynamic therapies, provide an
      alternative means for spatially and temporally controlled minimally invasive
      treatments of cancers. Nanomaterials can serve as nanocargoes for the delivery of
      chemo-drugs, diagnostic contrast reagents, and organic photosensitizers, and can
      be used to directly generate heat or reactive oxygen species for the treatment of
      tumors without the need for organic photosensitizers with NIR-light irradiation.
      Here, current progress in NIR-light-activated nanomaterial-mediated photothermal
      therapy and photodynamic therapy is summarized. Furthermore, the effects of size,
      shape, and surface functionalities of nanomaterials on intracellular uptake,
      macrophage clearance, biodistribution, cytotoxicities, and biomedical efficacies
      are discussed. The use of various types of nanomaterials, such as gold
      nanoparticles, carbon nanotubes, graphene, and many other inorganic
      nanostructures, in combination with diagnostic and therapeutic modalities for
      solid tumors, is briefly reviewed.

PMID- 29577459
TI  - Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma
      in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway.
AB  - This study was designed to investigate the precancerous lesions of gastric
      carcinoma (PLGC)-reversing mechanisms of astragaloside IV (ASIV) in N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG)-induced PLGC rats. All rats were sacrificed after
      10-week treatment. Gastric tissue was analyzed by using histopathology and
      electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF
      1alpha, CD147, and miRNA-34a were detected by Western blotting and Real-time
      Quantitative polymerase chain reaction (RT-qPCR). As histopathology and electron
      microscope showed, it can be clearly observed that the area of dysplasia was
      reduced in ASIV groups, indicating that MNNG-induced PLGC was markedly reversed
      by ASIV. Moreover, compared with model group, a significant decrease in gene
      expressions of LDHA, MCT1, MCT4, HIF-1alpha, CD147, and TIGAR was observed
      whereas miRNA-34a level was increased in ASIV groups. A significant up-regulation
      induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF-1alpha, and CD147 was
      attenuated in rats treated with ASIV. In contrast, the decreased expression of
      TIGAR was restored by ASIV. Interestingly, up-regulation of p53 expression
      induced by MNNG was further increased in ASIV groups. In brief, these results
      implied that abnormal glycolysis was relieved by ASIV via regulation of the
      expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF-1alpha, CD147, and miRNA-34a.

PMID- 29577460
TI  - Gene expression profiling reveals the plausible mechanisms underlying the
      antitumor and antimetastasis effects of Andrographis paniculata in esophageal
      cancer.
AB  - Esophageal cancer (EC) is a seriously invasive malignancy with high mortality and
      poor prognosis. Metastasis of EC is the major cause of mortality. Our studies
      previously demonstrated that a herbal medicine Andrographis paniculata (AP)
      significantly suppressed EC growth and metastasis in vitro and in vivo. However,
      the underlying mechanisms responsible for these effects have not yet been
      systematically elucidated. In this context, gene expression profiling of AP
      treated squamous EC cells (EC-109) was performed to reveal the regulatory
      mechanisms of AP in antitumor and antimetastasis signaling pathways using gene
      expression microarray analysis. Differentially expressed genes were identified by
      Affymetrix Gene Chip, followed by the real-time polymerase chain reaction
      validation. The results showed that the canonical pathways were significantly
      regulated by AP treatment, including multiple genes related to proliferation,
      apoptosis, intercellular adhesion, metastatic processes, and drug resistance,
      such as WNT, TGF-beta, MAPK and ErbB signaling pathways, and ATP-binding cassette
      transporter subfamily members. This genomic study emerges candidate molecular
      targets and pathways to reveal the mechanisms involved in AP's effects, which
      provides scientific evidence to support the clinical application of AP in EC
      treatment.

PMID- 29577461
TI  - Editorial Comment to Impact of age on quality of life in patients with localized
      prostate cancer treated with high-dose rate brachytherapy combined with external
      beam radiotherapy.

PMID- 29577462
TI  - Profiles of Women in Science: Prof. Dr. med. Kerstin Erika Schmidt of the Federal
      University of Rio Grande do Norte.

PMID- 29577463
TI  - Investigation of Bistetramethylammonium Hydrogencyclotriphosphate-A Molecular
      Rotor?
AB  - The crystalline phase beta-[N(CH3 )4 ]2 HP3 O9 undergoes a reversible phase
      transition to gamma-[N(CH3 )4 ]2 HP3 O9 , which was studied by dynamic scanning
      calorimetry and X-ray diffraction. The rotational dynamics of the anion [P3 O9 ]3
      were evident from variable temperature 31 P magic angle spinning (MAS) NMR
      spectroscopy. The rotational dynamics could be simulated with a 3-site jump
      model, which yields spectra in good agreement with experiment. An activation
      energy of 0.6 eV could be estimated from line shape analysis. Impedance spectra
      reflect a bulk proton conductivity of gamma-[N(CH3 )4 ]2 HP3 O9 of 6.9*10-5  S cm
      1 at 240  degrees C and an activation energy of approximately 1.0 eV. Thus this
      salt features bulk protonic motion, while local rotational anionic motion happens
      with activation energies of the same order, as suggested by the paddle-wheel
      mechanism.

PMID- 29577464
TI  - Snare with endoclips to assist in endoscopic submucosal dissection with mucosal
      internal traction for a gastric neoplasia involving pyloric ring.

PMID- 29577465
TI  - Visible Light Activation of Spin-Silenced Fluorescence.
AB  - A self-reporting, profluorescent, visible light-induced release system is
      introduced. Fluorescence activation is enabled by a mild remote trigger signal
      that can be monitored with the naked-eye in real time. The light-responsive spin
      silenced polymer is synthesized via an Ugi post-polymerization modification
      incorporating paramagnetic nitroxides and a light cleavable fluorophore moiety.

PMID- 29577466
TI  - Topology and Electronic Density Driven Generation of Alkali Cation Complexes.
AB  - The formation and characterization of K+ and Cs+ complexes originating from the
      cooperativity of three non-covalent interactions is explored. The tridimensional
      preorganization of the naphthothiophene platform displays a favorable well
      defined bay region combining a pi fragment and a carbonyl moiety flanking a
      central sulfur atom. A joint theoretical and experimental infrared multiple
      photon dissociation (IRMPD) study allowed deciphering the key contribution of the
      orthogonal phenyl fragment to the elaboration of alkali metal complexes. In
      combination with S and CO interactions, the pi-cation interaction significantly
      enhances the binding energies of naphthothiophene derivatives.

PMID- 29577467
TI  - Post-cationic Modification of a Pyrimidine-Based Conjugated Microporous Polymer
      for Enhancing the Removal Performance of Anionic Dyes in Water.
AB  - Ionic porous organic polymers have attracted much attention due to their broad
      applications in catalysis, energy storage/conversion, proton conduction, etc. In
      this paper, an ionic porous organic polymer, CMP-PM-Me, was synthesized through
      post-synthetic modification of a pyrimidine-based conjugated microporous polymer,
      CMP-PM, which was constructed by the palladium catalyzed Sonogashira reaction of
      1,3,5-triethynylbenzen and 2,5-dibromopyrimidine. These two polymers are porous
      with Brunauer-Emmett-Teller surface areas of 416 and 241 m2  g-1 for CMP-PM and
      CMP-PM-Me, respectively. Due to the cationic framework, CMP-PM-Me exhibits a much
      faster and more efficient adsorption performance to anionic dyes such as Congo
      red (CR) and methyl orange (MO) than that of CMP-PM with a neutral framework. The
      uptakes for CR are 400.0 mg g-1 for CMP-PM-Me and 344.8 mg g-1 for CMP-PM,
      respectively. Furthermore, CMP-PM-Me could quickly and drastically separate
      anionic dyes from the binary mixed solution of anionic and nonanionic dyes within
      a short time. This work not only enriches the family of ionic organic porous
      polymers and widens their synthetic utility, but also demonstrates their
      applications in the adsorption and separation of anionic dyes in water.

PMID- 29577469
TI  - Natural selection and neutral evolutionary processes contribute to genetic
      divergence in leaf traits across a precipitation gradient in the tropical oak
      Quercus oleoides.
AB  - The impacts of drought are expanding worldwide as a consequence of climate
      change. However, there is still little knowledge of how species respond to long
      term selection in seasonally dry ecosystems. In this study, we used QST -FST
      comparisons to investigate (i) the role of natural selection on population
      genetic differentiation for a set of functional traits related to drought
      resistance in the seasonally dry tropical oak Quercus oleoides and (ii) the
      influence of water availability at the site of population origin and in
      experimental treatments on patterns of trait divergence. We conducted a thorough
      phenotypic characterization of 1912 seedlings from ten populations growing in
      field and greenhouse common gardens under replicated watering treatments. We also
      genotyped 218 individuals from the same set of populations using eleven nuclear
      microsatellites. QST distributions for leaf lamina area, specific leaf area, leaf
      thickness and stomatal pore index were higher than FST distribution. Results were
      consistent across growth environments. Genetic differentiation among populations
      for these functional traits was associated with the index of moisture at the
      origin of the populations. Together, our results suggest that drought is an
      important selective agent for Q. oleoides and that differences in length and
      severity of the dry season have driven the evolution of genetic differences in
      functional traits.

PMID- 29577470
TI  - Giant Thermal Expansion in 2D and 3D Cellular Materials.
AB  - When temperature increases, the volume of an object changes. This property was
      quantified as the coefficient of thermal expansion only a few hundred years ago.
      Part of the reason is that the change of volume due to the variation of
      temperature is in general extremely small and imperceptible. Here, abnormal giant
      linear thermal expansions in different types of two-ingredient microstructured
      hierarchical and self-similar cellular materials are reported. The cellular
      materials can be 2D or 3D, and isotropic or anisotropic, with a positive or
      negative thermal expansion due to the convex or/and concave shape in their
      representative volume elements respectively. The magnitude of the thermal
      expansion coefficient can be several times larger than the highest value reported
      in the literature. This study suggests an innovative approach to develop
      temperature-sensitive functional materials and devices.

PMID- 29577468
TI  - Maternal-fetal cross talk through cell-free fetal DNA, telomere shortening,
      microchimerism, and inflammation.
AB  - There exists a strong correlation between unscheduled inflammation at the
      maternal-fetal interface and the continuum of pregnancy complications. In normal
      pregnancy, immunological tolerance is established to protect the semi-allogeneic
      fetus. There has been extensive research on how the immunity, endovascular
      trophoblast migration, and hormonal nexus are orchestrated during pregnancy at
      the maternal-fetal interface to program a normal pregnancy outcome. It is not
      clear what contributes to the plasticity of uterine immune tolerance, fetal
      survial, and long-term post-partum health of the mother and the offspring. Old
      and new concepts have reemerged and emerged that include cell-free fetal DNA
      (cffDNA), telomere shortening, microchimerism involving bidirectional migration
      of maternal and fetal cells, and pregnancy as a stress factor. The question is
      how these pathways converge in a gestational age-dependent manner to contribute
      to the health of the mother and the offspring later in life and respond to an
      array of inflammatory challenges. In this Review, we provide pertinent discussion
      on maternal-fetal cross talk through cffDNA, telomere shortening, and
      microchimerism in the context of inflammatory and anti-inflammatory settings,
      particularly how these pathways lead to normal and adverse pregnancy outcomes.

PMID- 29577472
TI  - Polypyridyl Metallo-Organic Assemblies for Electrochromic Applications.
AB  - Electrochromic films undergo optical changes in response to a redox stimulus.
      This intriguing phenomenon can be used for a wide range of applications,
      including smart windows, sensors, color displays, and memory elements. Despite
      the rapid progress of late, designing suitable electrochromic materials that
      offer low-cost production, appealing colors, and pronounced optical contrast with
      high efficiency, as well as long-term stability remains an engineering challenge.
      Solid-state metal oxides, liquid crystals, and organic polymers have been for
      many years the leading candidates, successfully making their way into commercial
      products. An alternative class of materials relies on metal complexes that can be
      processed from solution, offer a variety of colors, and have metal-centered
      stable and reversible redox chemistry. These metallo-organic materials possess a
      full range of electrochromic properties, including ultrahigh coloration
      efficiencies, and cyclic stability. Here, some of the recent scientific
      developments in this field are highlighted.

PMID- 29577471
TI  - Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and
      upregulation of vasoactive intestinal peptide in mouse ileum.
AB  - Reduced blood flow to the brain induces cerebral ischaemia, potentially causing
      central injury and peripheral complications including gastrointestinal (GI)
      dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy
      in the enteric nervous system (ENS), which is essential in regulating GI
      function. This study investigates if enteric neuropathy occurs after cerebral
      ischaemia, by analysing neuronal survival and relative numbers of vasoactive
      intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing
      neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral
      ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and
      global cerebral ischaemia, modelled with either transient occlusion of both
      common carotid arteries followed by reperfusion (GCIR) or chronic cerebral
      hypoperfusion (CCH) was performed on C56BL/6 mice. Sham-operated mice for each
      ischaemia model served as control. Ileum was collected after 1-17 weeks,
      depending on model, and analysed using morphometry and immunocytochemistry. For
      each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and
      relative proportions of neurons immunoreactive (IR) for nNOS or VIP were
      estimated. No alterations in mucosa or muscle layer thicknesses were noted in any
      of the groups. Loss of myenteric neurons and an increased number of VIP-IR
      submucous neurons were found in mouse ileum 7 days after pMCAO. None of the
      global ischaemia models showed any alterations in neuronal survival or relative
      numbers of VIP- and nNOS-IR neurons. We conclude that focal cerebral ischaemia
      and global cerebral ischaemia influence enteric neuronal survival differently.
      This is suggested to reflect differences in peripheral neuro-immune responses.

PMID- 29577473
TI  - A Supercompressible, Elastic, and Bendable Carbon Aerogel with Ultrasensitive
      Detection Limits for Compression Strain, Pressure, and Bending Angle.
AB  - Ultralight and compressible carbon materials have promising applications in
      strain and pressure detection. However, it is still difficult to prepare carbon
      materials with supercompressibility, elasticity, stable strain-electrical signal
      response, and ultrasensitive detection limits, due to the challenge in structural
      regulation. Herein, a new strategy to prepare a reduced graphene oxide (rGO)
      based lamellar carbon aerogels with unexpected and integrated performances by
      designing wave-shape rGO layers and enhancing the interaction among the rGO
      layers is demonstrated. Addition of cellulose nanocrystalline and low-molecular
      weight carbon precursors enhances the interaction among rGO layers and thus
      produces an ultralight, flexible, and superstable structure. The as-prepared
      carbon aerogel displays a supercompressibility (undergoing an extreme strain of
      99%) and elasticity (100% height retention after 10 000 cycles at a strain of
      30%), as well as stable strain-current response (at least 10 000 cycles).
      Particularly, the carbon aerogel is ultrasensitive for detecting tiny change in
      strain (0.012%) and pressure (0.25 Pa), which are the lowest detection limits for
      compressible carbon materials reported in the literature. Moreover, the carbon
      aerogel exhibits excellent bendable performance and can detect an ultralow
      bending angle of 0.052 degrees . Additionally, the carbon aerogel also
      demonstrates its promising application as wearable devices.

PMID- 29577474
TI  - Prospective evaluation of a combination of fungal biomarkers for the diagnosis of
      invasive fungal disease in high-risk haematology patients.
AB  - We prospectively evaluated a combination of fungal biomarkers in adult
      haematology patients with focus on their clinical utility at different time
      points during the course of infection. In total, 135 patients were monitored once
      to twice weekly for serum (1-3)-beta-d-glucan (BG), galactomannan (GM), bis
      methyl-gliotoxin and urinary d-arabinitol/l-arabinitol ratio. In all, 13 cases
      with proven or probable invasive fungal disease (IFD) were identified. The
      sensitivity of BG and GM at the time of diagnosis (TOD) was low, but within 2
      weeks from the TOD the sensitivity of BG was 92%. BG >800 pg/mL was highly
      specific for IFD. At a pre-test probability of 12%, both BG and GM had negative
      predictive values (NPV) >0.9 but low positive predictive values (PPV). In a
      subgroup analysis of patients with clinically suspected IFD (pre-test probability
      of 35%), the NPV was lower, but the PPV for BG was 0.86 at cut-off 160 pg/mL.
      Among IFD patients, 91% had patterns of consecutively positive and increasing BG
      levels. Bis-methyl-gliotoxin was undetectable in 15 patients with proven,
      probable and possible IA. To conclude, BG was the superior fungal marker for IFD
      diagnosis. Quantification above the limit of detection and graphical evaluation
      of the pattern of dynamics are warranted in the interpretation of BG results.

PMID- 29577475
TI  - Selectable high-yield recombinant protein production in human cells using a
      GFP/YFP nanobody affinity support.
AB  - Recombinant protein expression systems that produce high yields of pure proteins
      and multi-protein complexes are essential to meet the needs of biologists,
      biochemists, and structural biologists using X-ray crystallography and cryo
      electron microscopy. An ideal expression system for recombinant human proteins is
      cultured human cells where the correct translation and chaperone machinery are
      present. However, compared to bacterial expression systems, human cell cultures
      present several technical challenges to their use as an expression system. We
      developed a method that utilizes a YFP fusion-tag to generate recombinant
      proteins using suspension-cultured HEK293F cells. YFP is a dual-function tag that
      enables direct visualization and fluorescence-based selection of high expressing
      clones for and rapid purification using a high-stringency, high-affinity anti
      GFP/YFP nanobody support. We demonstrate the utility of this system by expressing
      two large human proteins, TOP2alpha (340 KDa dimer) and a TOP2beta catalytic core
      (260 KDa dimer). This robustly and reproducibly yields >10 mg/L liter of cell
      culture using transient expression or 2.5 mg/L using stable expression.

PMID- 29577476
TI  - Recent Advances in Intrinsic Self-Healing Cementitious Materials.
AB  - Self-healing is a natural phenomenon whereby living organisms respond to damage.
      Recently, considerable research efforts have been invested in self-healing
      cementitious materials that are capable of restoring structural integrity and
      mechanical properties after being damaged. Inspired by nature, a variety of
      creative approaches are explored here based on the intrinsic or extrinsic healing
      mechanism. Research on new intrinsic self-healing cementitious materials with
      biomimetic features is on the forefront of material science, which provides a
      promising way to construct resilient and sustainable concrete infrastructures.
      Here, the current advances in the development of the intrinsic healing
      cementitious materials are described, and a new definition of intrinsic self
      healing discussed. The methods to assess the efficiency of different healing
      mechanisms are briefly summarized. The critical insights are emphasized to guide
      the future research on the development of new self-healing cementitious
      materials.

PMID- 29577478
TI  - Uptake of the Victorian Government school and early childhood service health
      promotion framework in the City of Greater Geelong according to area-level
      socioeconomic position.
AB  - ISSUE ADDRESSED: Whole-of-setting initiatives have been recommended as an
      equitable approach to health promotion. However, there has been little analysis
      of differences in uptake of such approaches according to indicators of
      socioeconomic position. In Victoria, Australia, the Achievement Program is a
      state government health promotion initiative that uses a whole-of-setting
      approach in early childhood services, schools and workplaces. We conducted an
      exploratory comparison of uptake of and progression through the programme by
      schools and early childhood services in one local area, according to area-level
      socioeconomic position. METHODS: Approximately 3 years after programme
      initiation, we linked data on the progress of 89 early childhood services and 67
      primary schools to an area-level index of relative socioeconomic disadvantage. We
      compared uptake of and progression through the programme by setting (service or
      school) and quartiles of socioeconomic position. RESULTS: About 89% of early
      childhood services and 70% of primary schools had registered for the programme,
      with 18% and 15%, respectively, attaining the goal of completing the final stage.
      A greater proportion of settings in areas in the most disadvantaged quartile had
      registered for the programme and completed the final stage of the programme,
      compared with settings in areas in the least disadvantaged quartile. However,
      variation by socioeconomic position was not linear across quartiles. CONCLUSION:
      The Achievement Program did not appear to be inequitable in its uptake. Research
      into uptake in other local areas and outcomes achieved would be beneficial. SO
      WHAT?: This demonstrates that whole-of-setting approaches can potentially be an
      equity-enhancing approach to health promotion.

PMID- 29577479
TI  - Alcohol and injury risk at a Western Australian school Leavers Festival.
AB  - BACKGROUND: Leavers Festivals have become an institution for Australian youth to
      celebrate the completion of secondary school. Reported hazardous consumption of
      alcohol by leavers has focused concern on risk-taking behaviour. In response to
      this, campaigns such as "Don't Drink and Drown" have targeted youth to reduce
      alcohol consumption during aquatic activities. This research investigated
      intended and actual alcohol consumption, particularly during aquatic activities
      at a Leavers Festival located in the coastal town of Dunsborough, southern
      Western Australia. METHOD: In November 2016, 549 leavers aged 17 or 18 years
      completed a paper-based survey over a four-day period during the Festival.
      RESULTS: Overall, 90% of leavers reported intending to drink during the Festival,
      with expected average daily consumption being seven to nine standard drinks;
      reported daily consumption was five to six standard drinks (P < 0.001). Of the
      29% of leavers who consumed alcohol around water during Leavers, 47% had done so
      while swimming. About 91% were aware of the campaign "Don't Drink and Drown."
      CONCLUSION: Awareness of the "Don't Drink and Drown" campaign and knowledge of
      risks associated with alcohol consumption and swimming were relatively high.
      Intention and actual consumption of alcohol did not correlate, with daily
      consumption less than anticipated. SO WHAT: Leavers appear to have a reasonable
      level of awareness and knowledge of the risks associated with alcohol consumption
      and aquatic activities, which may reflect the impact of education campaigns.
      However, this knowledge is not always translated into nonrisky aquatic behaviour.

PMID- 29577477
TI  - Neutrophil-Based Drug Delivery Systems.
AB  - White blood cells (WBCs) are a major component of immunity in response to
      pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a
      central role in acute inflammation induced by pathogens. Adhesion to vasculature
      and tissue infiltration of neutrophils are key processes in acute inflammation.
      Many inflammatory/autoimmune disorders and cancer therapies have been found to be
      involved in activation and tissue infiltration of neutrophils. A promising
      strategy to develop novel targeted drug delivery systems is the targeting and
      exploitation of activated neutrophils. Herein, a new drug delivery platform based
      on neutrophils is reviewed. There are two types of drug delivery systems:
      neutrophils as carriers and neutrophil-membrane-derived nanovesicles. It is
      discussed how nanoparticles hijack neutrophils in vivo to deliver therapeutics
      across blood vessel barriers and how neutrophil-membrane-derived nanovesicles
      target inflamed vasculature. Finally, the potential applications of neutrophil
      based drug delivery systems in treating inflammation and cancers are presented.

PMID- 29577480
TI  - Methylation pattern variation between goats and rats during the onset of puberty.
AB  - Puberty is initiated by increased pulsatile gonadotropin-releasing hormone (GnRH)
      release from the hypothalamus. Epigenetic repression is thought to play a crucial
      role in the initiation of puberty, although the existence of analogous changes in
      methylation patterns across species is unclear. We analysed mRNA expression of
      DNA methyltransferases (DNMTs) and methyl-binding proteins (MBPs) in goats and
      rats by quantitative real-time PCR (qRT-PCR). DNA methylation profiles of
      hypothalamic were determined at the pre-pubertal and pubertal stages by
      bisulphite sequencing. In this study, expression of DNMTs and MBPs mRNA showed
      different patterns in goats and rats. Global methylation variation was low in
      goats and rats, and the profile remained stable during puberty. Gene ontology
      (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis revealed
      the involvement of 62 pathways in puberty in goats and rats including
      reproduction, type I diabetes mellitus and GnRH signalling pathways and found
      that Edn3, PTPRN2 and GRID1 showed different methylation patterns during puberty
      in goats and rats and similar variation patterns for Edn3 and PTPRN2 were showed.
      These indicated that Edn3 and PTPRN2 would play a role in the timing of puberty.
      This study provides evidence of the epigenetic control of puberty.

PMID- 29577481
TI  - Genetic architecture of traits associated with reproductive barriers in Silene:
      Coupling, sex chromosomes and variation.
AB  - The evolution of reproductive barriers and their underlying genetic architecture
      is of central importance for the formation of new species. Reproductive barriers
      can be controlled either by few large-effect loci suggesting strong selection on
      key traits, or by many small-effect loci, consistent with gradual divergence or
      with selection on polygenic or multiple traits. Genetic coupling between
      reproductive barrier loci further promotes divergence, particularly divergence
      with ongoing gene flow. In this study, we investigated the genetic architectures
      of ten morphological, phenological and life history traits associated with
      reproductive barriers between the hybridizing sister species Silene dioica and S.
      latifolia; both are dioecious with XY-sex determination. We used quantitative
      trait locus (QTL) mapping in two reciprocal F2 crosses. One to six QTLs per
      trait, including nine major QTLs (PVE > 20%), were detected on 11 of the 12
      linkage groups. We found strong evidence for coupling of QTLs for uncorrelated
      traits and for an important role of sex chromosomes in the genetic architectures
      of reproductive barrier traits. Unexpectedly, QTLs detected in the two F2 crosses
      differed largely, despite limited phenotypic differences between them and
      sufficient statistical power. The widely dispersed genetic architectures of
      traits associated with reproductive barriers suggest gradual divergence or
      multifarious selection. Coupling of the underlying QTLs likely promoted
      divergence with gene flow in this system. The low congruence of QTLs between the
      two crosses further points to variable and possibly redundant genetic
      architectures of traits associated with reproductive barriers, with important
      implications for the evolutionary dynamics of divergence and speciation.

PMID- 29577482
TI  - Testing Wallace's intuition: water type, reproductive isolation and divergence in
      an Amazonian fish.
AB  - Alfred Russel Wallace proposed classifying Amazon rivers based on their colour
      and clarity: white, black and clear water. Wallace also proposed that black
      waters could mediate diversification and yield distinct fish species. Here, we
      bring evidence of speciation mediated by water type in the sailfin tetra
      (Crenuchus spilurus), a fish whose range encompasses rivers of very distinct
      hydrochemical conditions. Distribution of the two main lineages concords with
      Wallace's water types: one restricted to the acidic and nutrient-poor waters of
      the Negro River (herein Rio Negro lineage) and a second widespread throughout the
      remaining of the species' distribution (herein Amazonas lineage). These lineages
      occur over a very broad geographical range, suggesting that despite occurring in
      regions separated by thousands of kilometres, individuals of the distinct
      lineages fail to occupy each other's habitats, hundreds of metres apart and not
      separated by physical barrier. Reproductive isolation was assessed in isolated
      pairs exposed to black-water conditions. All pairs with at least one individual
      of the lineage not native to black waters showed significantly lower spawning
      success, suggesting that the water type affected the fitness and contributed to
      reproductive isolation. Our results endorse Wallace's intuition and highlight the
      importance of ecological factors in shaping diversity of the Amazon fish fauna.

PMID- 29577483
TI  - What do women with substance use disorders want?

PMID- 29577486
TI  - Quintupling or quadrupling inhaled glucocorticoids to prevent asthma
      exacerbations?

PMID- 29577484
TI  - With Great Power Comes Great Responsibility.

PMID- 29577487
TI  - The effectiveness of contingency management in the treatment of patients with
      anorexia nervosa: A systematic review.
AB  - Contingency management in stipulating weight gain is routinely used in the
      treatment of anorexia nervosa, however, empirical investigations concerning its
      effectiveness have been scarce. This systematic review was conducted according to
      the PRISMA statement. Of N = 973 hits, 42 full-texts were included in the
      qualitative synthesis (11 theoretical texts, 19 case reports, 12 descriptive,
      cohort, and controlled trials). A central topic in the included publications
      concerns the enhancement of patients' autonomy through participation in the
      contingency management process. This heightened autonomy is achieved by using
      contingency contracts. Positive short-term effects on weight gain were shown,
      whereas follow-up results were heterogeneous. Although contingency contracts are
      widely used in clinical practice, our systematic review shows that empirical
      evidence on underlying mechanisms and efficacy is still scarce. Using an explicit
      treatment contract can enhance patients' motivation, compliance, and autonomy.
      Clinical practice should see further development including innovative motivation
      enhancing and conflict dissolving techniques in addressing the pronounced
      ambivalence often shown by patients with anorexia nervosa.

PMID- 29577488
TI  - Cytomorphology and sonographic features of ectopic thymic tissue diagnosed in
      paediatric FNA biopsies.
AB  - INTRODUCTION: Ectopic thymic tissue can arise as an asymptomatic neck mass, which
      may be detected on imaging studies. The aim of this study was to determine the
      incidence of ectopic thymic tissue in paediatric FNAs and to the correlate
      clinical, radiological and cytomorphological findings. METHODS: FNAs in children
      with neck and mediastinal lesions performed between January 2012 and July 2016
      were reviewed for cases of ectopic thymus. These were then evaluated and
      correlated with the cytology findings. RESULTS: Of 739 FNAs, 13 (1.8%) cases from
      11 patients showed ectopic thymic tissue. The targeted lesions were in the
      thyroid (n = 7), submandibular region (n = 1), superior mediastinum (n = 1) and
      paratracheal region (n = 1). The most common indication was for
      microcalcifications concerning for papillary thyroid carcinoma on ultrasound (n =
      6). Imaging findings included fusiform lesions with linear and punctuate bright
      echoes. The cytology evaluation showed small lymphocytes with discohesive
      epithelioid cells in most cases, and proteinaceous fluid in the cystic case.
      There were rare macrophages and Hassall's corpuscles. Flow cytometry and/or
      immunostains were performed in all cases, supporting thymic origin. CONCLUSION:
      Ectopic thymic tissue is rarely present as a neck mass or thyroid nodule on FNA
      biopsy. The ultrasound imaging findings reveal a well-defined fusiform lesion
      with punctate bright echoes that could be misinterpreted as papillary thyroid
      carcinoma. The aspirates show a small lymphoid population, immunophenotypically
      compatible with thymic T-cells, in addition to scattered epithelial cells.
      Therefore, knowledge of the typical ultrasonographic and cytopathological
      features can help make a definitive diagnosis and avoid more invasive procedures
      in paediatric patients.

PMID- 29577489
TI  - Alternative evaluation metrics for risk adjustment methods.
AB  - Risk adjustment is instituted to counter risk selection by accurately equating
      payments with expected expenditures. Traditional risk-adjustment methods are
      designed to estimate accurate payments at the group level. However, this
      generates residual risks at the individual level, especially for high-expenditure
      individuals, thereby inducing health plans to avoid those with high residual
      risks. To identify an optimal risk-adjustment method, we perform a comprehensive
      comparison of prediction accuracies at the group level, at the tail
      distributions, and at the individual level across 19 estimators: 9 parametric
      regression, 7 machine learning, and 3 distributional estimators. Using the 2013
      2014 MarketScan database, we find that no one estimator performs best in all
      prediction accuracies. Generally, machine learning and distribution-based
      estimators achieve higher group-level prediction accuracy than parametric
      regression estimators. However, parametric regression estimators show higher tail
      distribution prediction accuracy and individual-level prediction accuracy,
      especially at the tails of the distribution. This suggests that there is a trade
      off in selecting an appropriate risk-adjustment method between estimating
      accurate payments at the group level and lower residual risks at the individual
      level. Our results indicate that an optimal method cannot be determined solely on
      the basis of statistical metrics but rather needs to account for simulating
      plans' risk selective behaviors.

PMID- 29577490
TI  - A Qualitative Analysis of Patients' Perceptions of Shared Decision Making in the
      Emergency Department: "Let Me Know I Have a Choice".
AB  - BACKGROUND AND OBJECTIVES: Despite increasing attention to the use of shared
      decision making (SDM) in the emergency department (ED), little is known about ED
      patients' perspectives regarding this practice. We sought to explore the use of
      SDM from the perspectives of ED patients, focusing on what affects patients'
      desired level of involvement and what barriers and facilitators patients find
      most relevant to their experience. METHODS: We conducted semistructured
      interviews with a purposive sample of ED patients or their proxies at two sites.
      An interview guide was developed from existing literature and expert consensus
      and based on a framework underscoring the importance of both knowledge and power.
      Interviews were recorded, transcribed, and analyzed in an iterative process by a
      three-person coding team. Emergent themes were identified, discussed, and
      organized. RESULTS: Twenty-nine patients and proxies participated. The mean age
      of participants was 56 years (range, 20 to 89 years), and 13 were female.
      Participants were diverse in regard to race/ethnicity, education, number of
      previous ED visits, and presence of chronic conditions. All participants wanted
      some degree of involvement in decision making. Participants who made statements
      suggesting high self-efficacy and those who expressed mistrust of the health care
      system or previous negative experiences wanted a greater degree of involvement.
      Facilitators to involvement included familiarity with the decision at hand,
      physicians' good communication skills, and clearly delineated options. Some
      participants felt that their own relative lack of knowledge, compared to that of
      the physicians, made their involvement inappropriate or unwanted. Many
      participants had no expectation for SDM and although they did want involvement
      when asked explicitly, they were otherwise likely to defer to physicians without
      discussion. Many did not recognize opportunities for SDM in their clinical care.
      CONCLUSIONS: This exploration of ED patients' perceptions of SDM suggests that
      most patients want some degree of involvement in medical decision making but more
      proactive engagement of patients by clinicians is often needed. Further research
      should examine these issues in a larger and more representative population.

PMID- 29577491
TI  - A Free Silanide from Nucleophilic Substitution at Silicon(II).
AB  - A computationally guided synthetic route to a free silanide derived from tris(3
      methylindol-2-yl)methane ([(tmim)Si]- ) through nucleophilic substitution on the
      SiII precursor (Idipp)SiCl2 is reported (Idipp=2,3-dihydro-1,3-bis(2,6
      diisopropylphenyl)-1H-imidazol-2-ylidene). This approach circumvents the need for
      strained tetrahedral silanes as synthetic intermediates. Computational
      investigations show that the electron-donating properties of [(tmim)Si]- are
      close to those of PMe3. Experimentally, the [(tmim)Si]- anion is shown to undergo
      clean complexation to the base metal salts CuCl and FeCl2 , demonstrating the
      potential utility as a supporting ligand.

PMID- 29577492
TI  - Nitric oxide synthase and oxidative-nitrosative stress play a key role in
      placental infection by Trypanosoma cruzi.
AB  - PROBLEM: The innate immune response of the placenta may participate in the
      congenital transmission of Chagas disease through releasing reactive oxygen and
      nitrogen intermediates. METHOD OF STUDY: Placental explants were cultured with 1
      * 106 and 1 * 105 trypomastigotes of Tulahuen and Lucky strains and controls
      without parasites, and with the addition of nitric oxide synthase inhibitor
      Nomega-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the
      reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast
      (STB) was examined by histological analysis, and the nitric oxide synthase,
      endothelial (eNOS), and nitrotyrosine expressions were analyzed by
      immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels
      in the culture supernatant through ELISA assays. Parasite load with qPCR using
      Taqman primers was quantified. RESULTS: The higher number of T. cruzi (106 )
      increased placental infection, eNOS expression, nitrosative stress, and STB
      detachment, with the placental barrier being injured by oxidative stress.
      CONCLUSION: The higher number of parasites caused deleterious consequences to the
      placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage
      caused by trypomastigotes in placental villi but not that of the infection.
      Moreover, trophoblast eNOS played a key role in placental infection with the
      highest inoculum of Lucky, demonstrating the importance of the enzyme and
      nitrosative-oxidative stress in Chagas congenital transmission.

PMID- 29577493
TI  - 2SLS versus 2SRI: Appropriate methods for rare outcomes and/or rare exposures.
AB  - This study used Monte Carlo simulations to examine the ability of the two-stage
      least squares (2SLS) estimator and two-stage residual inclusion (2SRI) estimators
      with varying forms of residuals to estimate the local average and population
      average treatment effect parameters in models with binary outcome, endogenous
      binary treatment, and single binary instrument. The rarity of the outcome and the
      treatment was varied across simulation scenarios. Results showed that 2SLS
      generated consistent estimates of the local average treatment effects (LATE) and
      biased estimates of the average treatment effects (ATE) across all scenarios.
      2SRI approaches, in general, produced biased estimates of both LATE and ATE under
      all scenarios. 2SRI using generalized residuals minimized the bias in ATE
      estimates. Use of 2SLS and 2SRI is illustrated in an empirical application
      estimating the effects of long-term care insurance on a variety of binary health
      care utilization outcomes among the near-elderly using the Health and Retirement
      Study.

PMID- 29577494
TI  - Placenta immune infiltrates and perinatal outcomes.
AB  - Pregnancy is a state of immunotolerance and loss of this immunotolerance may lead
      to fetal rejection, pregnancy complications, and neonatal complications.
      Immunobiology of pregnancy is complex and involves unique immune cell populations
      specific to pregnancy, changes in mucosal immune cells and peripheral immune
      system, and reciprocal adaptations between the mother and the fetus. The
      mechanisms required for sustaining a healthy feto-placental barrier and a healthy
      pregnancy such as activation of regulatory immune responses with a predominance
      of regulatory T cells lead to immune evasion and propagation of cancer. It is
      intriguing to note that the immune pathways which are effective in limiting or
      eliminating cancer form the very basis for loss of feto-maternal tolerance. In
      this article, we aim to compare and contrast immunobiology of healthy and
      pathological pregnancies mirroring with cancer immunobiology with a focus on
      immune checkpoint receptors.

PMID- 29577495
TI  - HCV genotype 4, 5 and 6: Distribution of viral subtypes and sustained virologic
      response rates in clinical trials of approved direct-acting antiviral regimens.
AB  - Multiple direct-acting antiviral (DAA)-based regimens are now available for all
      hepatitis C virus (HCV) genotypes (GTs). Because HCV GT 4, 5 and 6 are less
      common in the United States (US) and worldwide, relatively small numbers of
      participants with these GTs were evaluated in individual clinical trials. To
      provide a comprehensive description of subtype diversity and treatment outcomes
      in clinical trials for these less common GTs, we analysed data from 744
      participants with HCV GT4 (n = 573), GT5 (n = 81), or GT6 (n = 90) across 18
      clinical trials of DAA regimens. These data are from US New Drug Applications
      submitted between 2014 and 2017, and our analyses included only approved
      regimens. Excluding unresolved or mixed subtypes, the distribution of reported
      GT4 subtypes was 49% 4a, 31% 4d and 16% for one of 14 other subtypes. The
      distribution of GT6 subtypes was 39% 6a, 27% 6e, 8% 6 L and 23% for one of 11
      other subtypes. Across approved regimens, sustained virologic response rates 12
      weeks post-treatment (SVR12) for GT 4, 5 and 6 ranged from 91% to 100%, 93% to
      97% and 96% to 100%, respectively. SVR12 by GT4 subtype ranged from 96% to 100%
      for 4a and 81% to 100% for 4d. Virologic failures occurred in GT 4a, 4b, 4d and
      4r. For GT6, SVR12 was 100% for all subtypes except 6 L, for which 1 of 7
      participants experienced virologic failure. To our knowledge, this is the largest
      compilation of HCV GT 4, 5 or 6 clinical trial data. These analyses may be useful
      for clinicians treating HCV GT 4, 5 or 6.

PMID- 29577496
TI  - Transcranial direct current stimulation for upper limb neuropathic pain: A double
      blind randomized controlled trial.
AB  - BACKGROUND: While promising, there are mixed findings for the efficacy of
      transcranial direct current stimulation (tDCS) for the management of chronic
      pain. The goal of this study was to evaluate the effect of anodal tDCS on pain
      and function in people with upper limb neuropathic pain. METHODS: The study was a
      double-blinded, randomized controlled trial. Thirty participants were randomly
      allocated into active and sham tDCS groups. Baseline assessments of pain and
      function, as well as quantitative sensory testing (QST) to probe the function of
      the nociceptive system, were undertaken prior to participants receiving 5 days of
      active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome
      measures were re-assessed 1, 3 and 8 weeks following the intervention. RESULTS:
      Group analyses revealed no significant improvement in pain, function, or QST
      measures over time in either group. However, there were significantly more
      individual responders (>=30% change in pain) in the active compared to the sham
      tDCS group at the final follow-up. In the active group, there was a significant
      correlation indicating those with higher baseline pain had greater pain relief.
      CONCLUSIONS: On group analyses, no evidence was provided that 1 mA tDCS is
      beneficial for people with upper limb neuropathic pain, although it may provide
      lasting pain relief for some individuals. SIGNIFICANCE: At the group level, we
      found no evidence that 5 days of active 1 mA tDCS is effective for people with
      upper limb neuropathic pain. However, there were more individual responders in
      the active tDCS group compared to sham, and those who responded early after
      treatment experienced sustained pain relief.

PMID- 29577497
TI  - Pliocene-Pleistocene ecological niche evolution shapes the phylogeography of a
      Mediterranean plant group.
AB  - Estimating species ability to adapt to environmental changes is crucial to
      understand their past and future response to climate change. The Mediterranean
      Basin has experienced remarkable climatic changes since the Miocene, which have
      greatly influenced the evolution of the Mediterranean flora. Here, we examine the
      evolutionary history and biogeographic patterns of two sedge sister species
      (Carex, Cyperaceae) restricted to the western Mediterranean Basin, but with
      Pliocene fossil record in central Europe. In particular, we estimated the
      evolution of climatic niches through time and its influence in lineage
      differentiation. We carried out a dated phylogenetic-phylogeographic study based
      on seven DNA regions (nDNA and ptDNA) and fingerprinting data (AFLPs), and
      modelled ecological niches and species distributions for the Pliocene,
      Pleistocene and present. Phylogenetic and divergence time analyses revealed that
      both species form a monophyletic lineage originated in the late Pliocene-early
      Pleistocene. We detected clear genetic differentiation between both species with
      distinct genetic clusters in disjunct areas, indicating the predominant role of
      geographic barriers limiting gene flow. We found a remarkable shift in the
      climatic requirements between Pliocene and extant populations, although the niche
      seems to have been relatively conserved since the Pleistocene split of both
      species. This study highlights how an integrative approach combining different
      data sources and analyses, including fossils, allows solid and robust inferences
      about the evolutionary history of a plant group since the Pliocene.

PMID- 29577499
TI  - Venous and autonomic function in formerly pre-eclamptic women and BMI-matched
      controls.
AB  - INTRODUCTION: Pre-pregnancy reduced plasma volume increases the risk on
      subsequent pre-eclamptic pregnancy. Reduced plasma volume is thought to reflect
      venous reserve capacity, especially when venous vasculature is constricted and
      sympathetic tone is elevated. As obesity might affect these variables and also
      relates to pre-eclampsia, increased body weight may underlie these observations.
      We hypothesized that the relationship between reduced venous reserve and
      preeclampsia is independent of body mass index (BMI). METHODS: We compared the
      non-pregnant venous reserve capacity in 30 formerly pre-eclamptic women, equally
      divided in 3 BMI-classes (BMI 19.5-24.9, BMI 25-29.9, BMI >=30) to 30 controls.
      Cases and controls were matched for BMI, age and parity. The venous reserve
      capacity was quantified by assessing plasma volume and venous compliance. The
      autonomic nervous system regulating the venous capacitance was evaluated with
      heart rate variability analysis in resting supine position and during positive
      head-up tilt (HUT). RESULTS: Formerly pre-eclamptic women had in supine position
      lower plasma volume than controls (1339 +/- 79 vs 1547 +/- 139 ml/m2 (p<0.001)),
      lower venous compliance (0.04 +/- 0.02 vs 0.07 +/- 0.02 ml/dl/mmHg (p<0.001)),
      higher sympathetic tone (1.9 +/- 0.1 vs 1.2 +/- 0.7 mmHg2 (p=0.002)) and lower
      baroreceptor sensitivity (8.7 +/- 3.8 vs 19.0 +/- 1.7 ms/mmHg (p<0.001)). During
      HUT, women with a history of preeclampsia have less modulatory capacity over
      venous compliance and baroreceptor sensitivity, while heart rate and sympathetic
      tone remain consistently higher. CONCLUSION: Women with a history of pre
      eclampsia have, compared to BMI-matched controls, reduced venous reserve
      capacity. This is reflected by lower plasma volume and venous compliance, the
      autonomic balance is shifted towards sympathetic dominance and lower baroreceptor
      sensitivity. This suggests that not BMI, but underlying reduced venous reserve
      relates to pre-eclampsia.

PMID- 29577498
TI  - Evaluation of multiple alternative instrument platforms for targeted and non
      targeted dioxin and furan analysis.
AB  - The use of gas chromatography coupled to high-resolution magnetic sector mass
      spectrometers (GC-HRMS) is well established for dioxin and furan analysis.
      However, the use of gas chromatography coupled to triple quadrupole (MS/MS) and
      time of flight (TOF) mass spectrometers with atmospheric pressure ionization
      (API) and traditional electron ionization (EI) for dioxin and furan analysis is
      emerging as a viable alternative to GC-HRMS screening. These instruments offer
      greater versatility in the lab for a wider range of compound identification and
      quantification as well as improved ease of operation. The instruments utilized in
      this study included 2 API-MS/MS, 1 traditional EI-MS/MS, an API-quadrupole time
      of flight mass spectrometer (API-QTOF), and a EI-high-resolution TOF (EI-HRTOF).
      This study compared these 5 instruments to a GC-HRMS using method detection limit
      (MDLs) samples for dioxin and furan analysis. Each instrument demonstrated
      acceptable MDL values for the 17 chlorinated dioxin and furans studied. The API
      MS/MS instruments provide the greatest overall improvement in MDL value over the
      GC-HRMS with a 1.5 to 2-fold improvement. The API-QTOF and EI-TOF demonstrate
      slight increases in MDL value as compared with the GC-HRMS with a 1.5-fold
      increase. The 5 instruments studied all demonstrate acceptable MDL values with no
      MDL for a single congener greater than 5 times that for the GC-HRMS. All 5
      instruments offer a viable alternative to GC-HRMS for the analysis of dioxins and
      furans and should be considered when developing new validated methodologies.

PMID- 29577500
TI  - Hybridization could be a common phenomenon within the highly diverse lizard genus
      Liolaemus.
AB  - Hybridization is likely to occur more often between closely related taxa that
      have had insufficient time to diverge to the point of reproductive
      incompatibility; hybridization between deeply divergent lineages is rare. In
      squamate reptiles, hybridization has been proposed as a possible explanation for
      the extensive paraphyly observed in mitochondrial gene trees in several species
      complexes of the South American lizard genus Liolaemus. One of the best
      documented cases is within the L. boulengeri and L. rothi complexes, which
      diverged ~5.5 million years ago. Here, we describe a comprehensive study for
      approaching the hybridization hypothesis between these lizard species complexes.
      We explored the level of gene tree discordance using the novel 'extra lineage
      contribution' statistics (XLC, presented in this study) that quantifies the level
      of gene tree discordance contribution per individual within a species. We
      included molecular data (12 nuclear and two mitochondrial genes) from 127
      individuals, and results of a coalescent model-based analysis show that the most
      likely explanation for the gene tree-species tree discordance is interspecific
      hybridization. Our best-supported hypothesis suggests current and past
      hybridization between L. rothi (rothi complex) and L. tehuelche (boulengeri
      complex), and independently between L. rothi and L. boulengeri and L. telsen
      (boulengeri complex). The hybrid descendants are characterized by intermediate
      phenotypes between the parental species, but are more similar to L. rothi in body
      size. We discuss the possible role of hybridization in Liolaemus evolution.

PMID- 29577501
TI  - The ART of brain expression.
AB  - When trying to find a mate, one might think about using a dating app. Imagine
      that someone else has installed the same app and tries to access the same
      potential mates that you have chosen, and that this someone uses false facts
      about himself/herself to increase the chance of dating someone before you or
      anyone else with honest status information does. Sounds familiar? It actually is,
      and in no way is such comportment restricted to human courtship behaviour.
      Alternative reproductive tactics (ARTs) are widespread in the animal kingdom. In
      this issue of Molecular Ecology, Cardoso, Goncalves, Goesmann, Canario, and
      Oliveira () investigate plastic ARTs of the peacock blenny (Salaria pavo), in
      which males occur in three morphs: nestholders, sneakers and transitionals
      between the two former. They apply transcriptome sequencing to answer the
      question how brain gene expression contributes to sex role-specific behaviour and
      to intersex phenotypes.

PMID- 29577502
TI  - Do parasites and antioxidant availability affect begging behaviour, growth rate
      and resistance to oxidative stress?
AB  - Early-life trade-offs faced by developing offspring can have long-term
      consequences for their future fitness. Young offspring use begging displays to
      solicit resources from their parents and have been selected to grow fast to
      maximize survival. However, growth and begging behaviour are generally traded off
      against self-maintenance. Oxidative stress, a physiological mediator of life
      history trade-offs, may play a major role in this trade-off by constraining, or
      being costly to, growth and begging behaviour. Yet, despite implications for the
      evolution of life-history strategies and parent-offspring conflicts, the
      interplay between growth, begging behaviour and resistance to oxidative stress
      remains to be investigated. We experimentally challenged wild great tit (Parus
      major) offspring by infesting nests with a common ectoparasite, the hen flea
      (Ceratophyllus gallinae), and simultaneously tested for compensating effects of
      increased vitamin E availability, a common dietary antioxidant. We further
      quantified the experimental treatment effects on offspring growth, begging
      intensity and oxidative stress. Flea-infested nestlings of both sexes showed
      reduced body mass during the first half of the nestling phase, but this effect
      vanished short before fledging. Begging intensity and oxidative stress of both
      sexes were unaffected by both experimental treatments. Feeding rates were not
      affected by the experimental treatments, but parents of flea-infested nests fed
      nestlings with a higher proportion of caterpillars, the main source of
      antioxidants. Additionally, female nestlings begged significantly less than males
      in control nests, whereas both sexes begged at similar rates in vitamin E
      supplemented nests. Our study shows that a parasite exposure does not necessarily
      affect oxidative stress levels or begging intensity, but suggests that parents
      can compensate for negative effects of parasitism by modifying food composition.
      Furthermore, our results indicate that the begging capacity of the less
      competitive sex is constrained by antioxidant availability.

PMID- 29577503
TI  - Comparison between potassium chloride and lidocaine as lethal agents for feticide
      for the termination of pregnancy.
AB  - In France, the practice of termination of pregnancy (TOP) can be performed
      regardless of gestational age in specific circumstances (a fetus that is highly
      likely to be affected by severe and uncorrectable condition or where the mother
      health is in danger and with medical approval).

PMID- 29577504
TI  - The modality and redundancy effects in multimedia learning in children with
      dyslexia.
AB  - The present study aimed to examine the modality and redundancy effects in
      multimedia learning in children with dyslexia in order to find out whether their
      learning benefits from written and/or spoken text with pictures. We compared
      study time and knowledge gain in 26 11-year-old children with dyslexia and 38
      typically reading peers in a within-subjects design. All children were presented
      with a series of user-paced multimedia lessons in 3 conditions: pictorial
      information presented with (a) written text, (b) audio, or (c) combined text and
      audio. We also examined whether children's learning outcomes were related to
      their working memory. With respect to study time, we found modality and reversed
      redundancy effects. Children with dyslexia spent more time learning in the text
      condition, compared with the audio condition and the combined text-and-audio
      condition. Regarding knowledge gain, no modality or redundancy effects were
      evidenced. Although the groups differed on working memory, it did not influence
      the modality or redundancy effect on study time or knowledge gain. In multimedia
      learning, it thus is more efficient to provide children with dyslexia with audio
      or with auditory support.

PMID- 29577505
TI  - Efficacy and safety of bilateral thoracic paravertebral blocks in outpatient
      breast surgery.
AB  - Unilateral thoracic paravertebral blocks (TPVBs) have demonstrated reliable
      intraoperative analgesia, low postoperative pain scores, and an opioid-sparing
      effect in breast cancer surgery. However, secondary to the perceived risk of
      complications, bilateral TPVB have been less well accepted and are less
      frequently used. The purpose of this study was to evaluate the feasibility of
      using bilateral TPVBs in outpatient surgery for patients undergoing bilateral
      mastectomy with immediate implant-based reconstruction. Electronic medical
      records were retrospectively reviewed for patients receiving bilateral TPVBs for
      bilateral mastectomy with immediate implant-based reconstruction performed by a
      single surgeon from September 2012 to September 2015. Records were reviewed for
      incidence of complications, time to discharge, and incidence of unplanned
      admission or readmission. Clopper-Pearson method for binomial distribution was
      used to calculate confidence intervals for proportions. Forty-five patients
      undergoing bilateral mastectomy with immediate reconstruction received bilateral
      TPVBs. There were 4 TPVB-related complications, all of which were symptomatic
      hypotension or bradycardia (9%; 95% CI, 2%-21%). There was no incidence of
      symptomatic pneumothorax. Mean time to discharge readiness from the
      postanesthesia care unit (PACU) was 1.9 hours (SD = 1.0). Overall, 91% (n = 29)
      of the 32 patients scheduled for day surgery were discharged home as planned.
      Mean time from entry to PACU to home discharge for day surgery patients (n = 32)
      and planned admissions (n = 13) was 5.9 hours (SD = 4.3) and 16.3 hours (SD =
      3.6), respectively. There was no incidence of readmission following discharge.
      Bilateral TPVBs can safely facilitate day surgery in carefully selected patients
      undergoing bilateral mastectomy with immediate implant-based reconstruction.

PMID- 29577506
TI  - The role of epistatic interactions underpinning resistance to parasitic Varroa
      mites in haploid honey bee (Apis mellifera) drones.
AB  - The Red Queen hypothesis predicts that host-parasite coevolutionary dynamics can
      select for host resistance through increased genetic diversity, recombination and
      evolutionary rates. However, in haplodiploid organisms such as the honeybee (Apis
      mellifera), models suggest the selective pressure is weaker than in diploids.
      Haplodiploid sex determination, found in A. mellifera, can allow deleterious
      recessive alleles to persist in the population through the diploid sex with
      negative effects predominantly expressed in the haploid sex. To overcome these
      negative effects in haploid genomes, epistatic interactions have been
      hypothesized to play an important role. Here, we use the interaction between A.
      mellifera and the parasitic mite Varroa destructor to test epistasis in the
      expression of resistance, through the inhibition of parasite reproduction, in
      haploid drones. We find novel loci on three chromosomes which explain over 45% of
      the resistance phenotype. Two of these loci interact only additively, suggesting
      their expression is independent of each other, but both loci interact
      epistatically with the third locus. With drone offspring inheriting only one copy
      of the queen's chromosomes, the drones will only possess one of two queen alleles
      throughout the years-long lifetime of the honeybee colony. Varroa, in comparison,
      completes its highly inbred reproductive cycle in a matter of weeks, allowing it
      to rapidly evolve resistance. Faced with the rapidly evolving Varroa, a diversity
      of pathways and epistatic interactions for the inhibition of Varroa reproduction
      could therefore provide a selective advantage to the high levels of recombination
      seen in A. mellifera. This allows for the remixing of phenotypes despite a fixed
      queen genotype.

PMID- 29577507
TI  - The volume and type of unhealthy bus shelter advertising around schools in Perth,
      Western Australia: Results from an explorative study.
AB  - ISSUE ADDRESSED: Exposure to advertising for unhealthy food, alcohol and gambling
      has been shown to influence children and adolescents' behaviours and attitudes.
      This exploratory study aimed to assess the volume and type of unhealthy bus
      shelter advertisements near schools in five local government areas in Perth,
      Western Australia and to monitor whether the volume of unhealthy advertisements
      varied seasonally. METHODS: The 29 local governments in the Perth metropolitan
      region were contacted seeking information regarding the locations of bus shelters
      featuring advertisements in their local government area. Five local governments
      provided sufficient information for an audit of the bus shelter advertisements in
      their area to be conducted. Every bus shelter within 500 m of a school was
      photographed and the type of advertisement recorded. The advertisements in the
      food, non-alcoholic beverage, alcohol, or gambling categories were then
      classified as being healthy, moderate, or unhealthy. This process was carried out
      in June, September, December 2016, and March 2017 to ascertain whether the type
      of advertisements displayed changed depending on the season. RESULTS: Of the 293
      advertisements recorded over the four audits, 31% featured unhealthy products, 3%
      moderate, and <1% healthy. Only two of the 293 advertisements were classified as
      being healthy. Seasonal variation in the volume of unhealthy advertisements was
      not identified. SO WHAT?: Western Australian school students are regularly
      exposed to unhealthy bus shelter advertisements. Stricter regulation of outdoor
      advertising is needed to ensure that young people are protected from the
      influence of unhealthy industries.

PMID- 29577508
TI  - Curriculum for neurogastroenterology and motility training: A report from the
      joint ANMS-ESNM task force.
AB  - Although neurogastroenterology and motility (NGM) disorders are some of the most
      frequent disorders encountered by practicing gastroenterologists, a structured
      competency-based training curriculum developed by NGM experts is lacking. The
      American Neurogastroenterology and Motility Society (ANMS) and the European
      Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the
      components of NGM training in North America and Europe. Eleven training domains
      were identified within NGM, consisting of functional gastrointestinal disorders,
      visceral hypersensitivity and pain pathways, motor disorders within anatomic
      areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders
      (gastro-esophageal reflux disease, other mucosal disorders), consequences of
      systemic disease, consequences of therapy (surgery, endoscopic intervention,
      medications, other therapy), and transition of pediatric patients into adult
      practice. A 3-tiered training curriculum covering these domains is proposed here
      and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected
      of all gastroenterology trainees and practicing gastroenterologists. Tier 2
      knowledge and training is appropriate for trainees who anticipate NGM disorder
      management and NGM function test interpretation being an important part of their
      careers, which may require competency assessment and credentialing of test
      interpretation skills. Tier 3 knowledge and training is undertaken by trainees
      interested in a dedicated NGM career and may be restricted to specific domains
      within the broad NGM field. The joint ANMS and ESNM task force anticipates that
      the NGM curriculum will streamline NGM training in North America and Europe and
      will lead to better identification of centers of excellence where Tier 2 and Tier
      3 training can be accomplished.

PMID- 29577509
TI  - Comorbidity between pain and mental illness - Evidence of a bidirectional
      relationship.
AB  - BACKGROUND: Pain from various locations in the body and mental illness are common
      and the comorbidity between the two is well-known although the temporal
      relationship remains to be determined. Our aim was to follow patients over time
      to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an
      increased risk of developing mental illness (here depression/anxiety) and/or the
      reverse, that is whether patients with mental illness have an increased risk to
      develop pain or fibromyalgia, compared to the rest of the population. METHODS:
      This prospective cohort study used the Skane Healthcare Register, covering all
      care in the region of Skane, southern Sweden (population ~1.3 million). The
      cohort included healthcare consultations in primary care, outpatient specialized
      care and inpatient care between 2007 and 2016 for all patients without prior
      registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365).
      RESULTS: The incidence rate ratio (IRR) for developing mental illness after pain
      was 2.18 (95% CI = 2.14-2.22) compared to without pain. IRR for developing pain
      after mental illness was 2.02 (95% CI = 1.98-2.06) compared to without mental
      illness. Corresponding IRR for developing mental illness after fibromyalgia was
      4.05 (95% CI = 3.58-4.59) and for developing fibromyalgia after mental illness
      5.54 (95% CI = 4.99-6.16). CONCLUSIONS: This study shows a bidirectional
      influence of similar magnitude of pain and mental illness, respectively. In
      monitoring patients with pain or mental illness, a focus on both conditions is
      thus important to develop appropriate, targeted interventions and may increase
      the likelihood of improved outcomes. SIGNIFICANCE: We followed a population-based
      cohort over a period of 10 years, including incident cases of both exposure and
      outcome and found a bidirectional relationship between pain and mental illness.
      Clinicians need to pay attention on both conditions, in patients seeking care due
      to mental illness or pain.

PMID- 29577510
TI  - Successful treatment with steroid and cyclosporine A in a patient with
      immunoglobulin A-proliferative glomerulonephritis with monoclonal immunoglobulin
      deposits.
AB  - We report a case of glomerulonephritis with monoclonal immunoglobulin (Ig) A
      deposits as a form of monoclonal gammopathy of renal significance (MGRS) caused
      by monoclonal immunoglobulins without blood disorders in a 41-year-old woman. She
      developed lower leg oedema and was hospitalized because of nephrotic syndrome.
      Serum and urine were negative for M protein, and the free light chain
      kappa/lambda ratio was within the normal range. Renal histopathological findings
      included mesangial proliferation, endocapillary cell proliferation, and a double
      contour appearance of the capillary walls. Immunofluorescent staining indicated
      IgA and C3 deposits on the mesangium and capillary walls. Only lambda chain and
      IgA1 deposits were noted. Fine granular sub-endothelial deposits with no specific
      structure were observed under electron microscopy. The patient was diagnosed with
      IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits (IgA
      PGNMID). The patient had decreased urine protein and sediment erythrocytes after
      she underwent two rounds of steroid pulse therapy and oral steroid therapy, but
      proteinuria and haematuria still remained. Four months later, the patient was
      administered 50 mg/day cyclosporine (CsA), and proteinuria and haematuria
      dramatically decreased. Only few case reports have been published on IgA-PGNMID.
      This case is rare in that the patient achieved successful treatment using a
      combination of steroids and CsA.

PMID- 29577511
TI  - Association between interleukin 8-receptor gene (CXCR1 and CXCR2) polymorphisms
      and urinary tract infection: evidence from 4097 subjects.
AB  - The aim of this study was to determine whether a correlation exists between
      interleukin-8 receptor polymorphisms and urinary tract infection (UTI)
      susceptibility. We systematically searched electronic databases including PubMed,
      Embase, China National Knowledge Infrastructure, and Web of Science up to
      November 5, 2017 to select appropriate studies that focused on C-X-C chemokine
      receptor type 1 and/or 2 (CXCR1, CXCR2) polymorphisms with susceptibility to UTI.
      Eight case-control studies including 2085 patients with UTI and 2012 controls
      were enrolled in this study. Seven studies of CXCR1 rs2234671 and two studies of
      rs3138086 were included in the meta-analyses. Pooled odds ratio (OR) and
      corresponding 95% confidence interval (CI) were synthesized using fixed-effects
      or random-effects model according to heterogeneity. No significant correlations
      were found between CXCR1 rs2234671 and rs3138086 polymorphisms and UTI
      susceptibility. However, subgroup analysis showed that rs2234671 was associated
      with an increased risk of UTI under allelic comparisons (C vs. G, OR = 1.95, 95%
      CI = 1.07-3.55), heterozygous model (GC vs. GG, OR = 1.93, 95% CI = 1.06-3.50),
      and dominant model (GC+CC vs. GG, OR = 1.98, 95% CI = 1.07-3.69) in children,
      especially in pediatric patients with acute pyelonephritis (allelic, OR = 2.43,
      95% CI = 1.28-4.60; heterozygous, OR = 2.40, 95% CI = 1.24-4.62; dominant, OR =
      2.48, 95% CI = 1.26-4.88). Furthermore, these results remained the same after
      eliminating paediatric patients with vesicoureteral reflux. CXCR1 rs2234671
      polymorphism might be associated with an increased risk of UTI in children.

PMID- 29577512
TI  - Cognitive remediation therapy (CRT) in a specialist inpatient eating disorder
      service for children and adolescents: CAN-CRT study protocol for a pilot
      randomised controlled trial.
AB  - INTRODUCTION: Research on treatments for young people (YP) with anorexia nervosa
      (AN) is scarce. Evidence supports the use of cognitive remediation therapy (CRT)
      to improve central coherence and set-shifting, inefficiencies that can negatively
      impact on prognosis. OBJECTIVE: The study aims to evaluate the feasibility of
      individual CRT in an inpatient setting for YP aged 10-18 years with AN and to
      qualitatively examine YP's and their parents experiences. METHOD: In a single
      centre, pilot, randomised controlled trial, 80 patients aged 10-18 years with AN
      will be randomly allocated to the immediate or delayed CRT group, in addition to
      standard treatment. A repeated measures design will be conducted across 3 time
      points. DISCUSSION: The data will provide evidence regarding the feasibility of
      individual CRT in YP with AN, informing directions of further development of CRT.
      The study is in preparation for a definitive randomised controlled trial. The aim
      of this manuscript is to describe the study protocol.

PMID- 29577513
TI  - Placental immune state shifts with gestational age.
AB  - PROBLEM: Placental immunologic functions are implicated in both the maintenance
      of a healthy pregnancy and the pathogenesis of obstetric complications. Immune
      populations at the maternal-fetal interface are hypothesized to support
      fetomaternal tolerance, defend the fetus from infection, and contribute to labor
      initiation. Despite the many potential roles of placental immune cells in normal
      and abnormal pregnancy, little is known about placental immune population
      dynamics over gestation, particularly near parturition. METHOD OF STUDY: A daily
      placental immune cell census was established in a murine model by flow cytometry
      from mid to late gestation and compared to the maternal systemic immune census.
      Shifts in the placental immune state were further characterized through cytokine
      ELISAs. RESULTS: The placental immune census is distinct from the maternal
      systemic immune census, although the cells are primarily maternal in origin. Near
      term parturition, the placenta contains fewer CD11c-positive myeloid cells and
      regulatory T cells, and there is a concurrent decrease in placental IL-9 and IL
      35. CONCLUSION: The immune profile of the placenta demonstrates a decrease in
      both regulatory immune cell types and cytokines late in gestation. Establishing
      the placental immune population dynamics over a healthy pregnancy will allow
      future investigation of placental immune cells during abnormal pregnancy.

PMID- 29577514
TI  - Gene expression profiles of ion channels and receptors in mouse resistance
      arteries: Effects of cell type, vascular bed, and age.
AB  - OBJECTIVE: Receptors and ion channels of smooth muscle cells (SMCs) and
      endothelial cells (ECs) are integral to the regulation of vessel diameter and
      tissue blood flow. Physiological roles of ion channels and receptors in skeletal
      muscle and mesenteric arteries have been identified; however, their gene
      expression profiles are undefined. We tested the hypothesis that expression
      profiles for ion channels and receptors governing vascular reactivity vary with
      cell type, vascular bed, and age. METHODS: Mesenteric and superior epigastric
      arteries were dissected from Old (24-26 months) and Young (3-6 months) C57BL/6J
      mice. ECs and SMCs were collected for analysis with custom qRT-PCR arrays to
      determine expression profiles of 80 ion channel and receptor genes.
      Bioinformatics analyses were applied to gain insight into functional
      interactions. RESULTS: We identified 68 differences in gene expression with
      respect to cell type, vessel type, and age. Heat maps illustrate differential
      expression, and distance matrices predict patterns of coexpression. Gene networks
      based upon protein-protein interaction datasets and KEGG pathways illustrate
      biological processes affected by specific differences in gene expression.
      CONCLUSIONS: Differences in gene expression profiles are most pronounced between
      microvascular ECs and SMCs with subtle variations between vascular beds and age
      groups.

PMID- 29577515
TI  - Impact of previous hepatitis B infection on the clinical outcomes from chronic
      hepatitis C? A population-level analysis.
AB  - Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is
      associated with adverse liver outcomes. The clinical impact of previous HBV
      infection on liver disease in HCV infection is unknown. We aimed at determining
      any association of previous HBV infection with liver outcomes using antibodies to
      the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The
      Scottish Hepatitis C Clinical Database containing data for all patients attending
      HCV clinics in participating health boards was linked to the HBV diagnostic
      registry and mortality data from Information Services Division, Scotland.
      Survival analyses with competing risks were constructed for time from the first
      appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver
      related mortality. Records of 8513 chronic HCV patients were included in the
      analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb
      positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause
      specific proportional hazards models showed previous HBV infection (HBcAb
      positive and HBsAg negative) significantly increased the risks of decompensated
      cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI:
      1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is
      the largest study to date showing an association between previous HBV infection
      and certain adverse liver outcomes in HCV infection. Our analyses add
      significantly to evidence which suggests that HBV infection adversely affects
      liver health despite apparent clearance. This has important implications for HBV
      vaccination policy and indications for prioritization of HCV therapy.

PMID- 29577516
TI  - Phylogenetic and phylodynamic analyses of hepatitis C virus subtype 1a in
      Okinawa, Japan.
AB  - Okinawa Island, located in Southern Japan, has a higher prevalence rate of
      hepatitis C virus subtype 1a (HCV-1a) infection than that in mainland Japan.
      Okinawa has a history of US military occupation after World War II. To elucidate
      the transmission history of HCV-1a in Okinawa, 26 whole-genome sequences were
      obtained from 29 patients during 2011-2016. Phylogenetic trees were reconstructed
      to identify the origin and characteristics of HCV-1a in Okinawa with
      epidemiological information. A phylogenetic tree based on whole-genome sequencing
      revealed that all of the samples were located below the US branches.
      Additionally, we identified one cluster comprised of 17 strains (Okinawa, n = 16;
      United States, n = 1). The majority of the patients in this cluster were people
      who inject drugs (PWID), indicating the presence of a people who inject drugs
      (PWID) cluster. Subsequently, Bayesian analyses were employed to reveal viral
      population dynamics. Intriguingly, a phylodynamic analysis uncovered a
      substantial increase in effective population size of HCV-1a from 1965 to 1980 and
      a slight increase in mid-2000, which were associated with an increase in illicit
      drug use in Okinawa. The estimated divergence time of the PWID cluster was 1967.6
      (1964.2-1971.1). These findings suggest that HCV-1a was introduced into Okinawa
      from the United States in the late 1960s, coincident with the Vietnam War.
      Subsequently, HCV-1a might have spread among the Japanese population with the
      spread of injecting drug use. Our study provides an understanding of HCV
      transmission dynamics in Okinawa, as well as the key role of PWID in HCV
      transmission.

PMID- 29577517
TI  - Analysis of Metabolomic Changes in Mesenchymal Stem Cells on Treatment with
      Desferrioxamine as a Hypoxia Mimetic Compared with Hypoxic Conditions.
AB  - Mesenchymal stem cells (MSCs) are commonly used in regenerative medicine, but
      their therapeutic effects vary depending on the culture environment. Hypoxic
      culturing can be used to maintain stem cells in an undifferentiated state, but is
      expensive and difficult to perform. The aim of this study was to determine the
      effectiveness of desferrioxamine (DFO), a hypoxia-mimetic reagent, as an
      alternative to hypoxic culturing by analyzing metabolic changes in MSCs under
      hypoxic conditions compared with changes induced by DFO. Low concentrations of
      DFO reduced mitochondrial activity and apoptosis. Therefore, low concentrations
      of DFO may be useful for MSC preconditioning. Metabolome analysis showed that
      both hypoxic treatment and DFO administration exhibited similar metabolite
      patterns except purine, pyrimidine, and tricarboxylic acid cycle (TCA) cycle
      related metabolites. Therefore, the use of DFO at low concentrations is a
      potential substitute for hypoxic culturing. These findings may form the
      foundation for the development of future regenerative therapies using MSCs. Stem
      Cells 2018;36:1226-1236.

PMID- 29577518
TI  - Quantification of serum markers of hepatitis B (HBV) and Delta virus (HDV)
      infections in patients with chronic HDV infection.
AB  - The interplay between hepatitis B (HBV) and delta (HDV) viruses is complex and
      not always characterized during chronic HDV infection. We assessed the clinical
      usefulness of new quantitative assays for HBV and HDV serum markers in a
      retrospective cross-sectional study. Sera obtained from 122 HDV genotype 1 and
      HBV genotype D coinfected, anti-HIV-negative patients (71 males; median age 49.8
      [21.7-66.9] years), recruited consecutively in two geographical areas (Italy 69
      patients, Romania 53 patients) with different HBV and HDV epidemiology, were
      tested for HBsAg, HBV-DNA, HBcrAg, total anti-HBc, HDV-RNA, IgM and total anti
      HDV using quantitative assays. Cirrhosis, which showed comparable prevalence in
      the two cohorts, was diagnosed in 97 of 122 (79.5%) patients. At multivariate
      analysis, cirrhosis was associated with lower total anti-HBc/IgM anti-HDV ratio
      (OR 0.990, 95% CI 0.981-0.999, P = .038), whereas disease activity was associated
      with higher total anti-HDV (OR 10.105, 95% CI 1.671-61.107, P = .012) and HDV-RNA
      levels (OR 2.366, 95% CI 1.456-3.844, P = .001). HDV-RNA serum levels showed a
      positive correlation with HBV-DNA (rho = 0.276, P = .005), HBsAg (rho = 0.404, P
      < .001) and HBcrAg (rho = 0.332, P < .001). The combined quantitative profiling
      of HBV and HDV serum markers identifies specific patterns associated with
      activity and stage of chronic hepatitis D (CHD). HDV pathogenicity depends on the
      underlying active HBV infection in spite of the inhibition of its replication.
      HDV-RNA, IgM anti-HDV, total anti-HDV, total anti-HBc, HBsAg and HBcrAg serum
      levels qualify for prospective studies to predict progressive CHD and identify
      candidates to antiviral therapy.

PMID- 29577519
TI  - Efficacy and safety of a T-type calcium channel blocker in patients with
      neuropathic pain: A proof-of-concept, randomized, double-blind and controlled
      trial.
AB  - BACKGROUND: T-type calcium channels have been shown to play an important role in
      the initiation and maintenance of neuropathic pain and represent a promising
      therapeutic target for new analgesic treatments. Ethosuximide (ETX), an
      anticonvulsant and a T-type channel blocker has shown analgesic effect in several
      chronic pain models but has not yet been evaluated in patients with neuropathic
      pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and
      randomized trial compared the efficacy and safety of ETX (given as add-on
      therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral
      neuropathic pain. After a 7-day run-in period, eligible patients aged over 18
      years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome
      was the difference between groups in the pain intensity (% of change from the
      baseline to end of treatment) assessed in the intention-to-treat population. This
      study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov
      (NCT02100046). RESULTS: The study was stopped during the interim analysis due to
      the high number of adverse events in the active treatment group. ETX failed to
      reduce total pain and showed a poor tolerance in comparison to IC. In the per
      protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI 
      25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033),
      but this result must be interpreted with caution because of a small subgroup of
      patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic
      pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This
      article shows that ETX is not effective to treat neuropathic pain. Nevertheless,
      per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work
      adds significant knowledge to preclinical and clinical data on the benefits of T
      type calcium channel inhibition for the treatment of neuropathic pain.

PMID- 29577520
TI  - The impact of thromboelastography on resuscitation in pediatric liver
      transplantation.
AB  - Although TEG directs effective resuscitation in adult surgical patients,
      pediatric data are lacking. We performed a retrospective comparative review of
      the effect of TEG on blood product utilization and outcomes following pediatric
      liver transplantation in 38 patients between 2008 and 2014. Diagnoses, laboratory
      values, fluid and blood product use, and outcomes were examined. Nineteen
      patients underwent liver transplantation prior to the implementation of TEG, and
      19 had perioperative TEG. The most common indications for transplant were BA (n =
      14), HB (n = 7), and metabolic disorders (n = 7). Intraoperative blood loss,
      urine output, fluid and blood product use were similar between groups. However,
      the use of fresh frozen plasma decreased significantly in TEG patients within the
      first 24 hours (29 vs 0 mL/kg, P < .01), and between 24 and 48 hours (12 vs 0
      mL/kg, P = .01) post-operatively. The total use of fresh frozen plasma during
      hospitalization was markedly reduced (111 vs 17 mL/kg, P < .01). Four patients in
      the TEG group had thromboembolic graft complications, including portal vein or
      hepatic artery thrombosis, and underwent retransplantation. The decreased use of
      fresh frozen plasma since implementation of TEG is an important finding for
      resource utilization and patient safety. However, the increased incidence of
      thromboembolic complications requires further investigation.

PMID- 29577521
TI  - How phonological awareness mediates the relation between working memory and word
      reading efficiency in children with dyslexia.
AB  - This study examined the relation between working memory, phonological awareness,
      and word reading efficiency in fourth-grade children with dyslexia. To test
      whether the relation between phonological awareness and word reading efficiency
      differed for children with dyslexia versus typically developing children, we
      assessed phonological awareness and word reading efficiency in 50 children with
      dyslexia (aged 9;10, 35 boys) and 613 typically developing children (aged 9;5,
      279 boys). Phonological awareness was found to be associated with word reading
      efficiency, similar for children with dyslexia and typically developing children.
      To find out whether the relation between working memory and word reading
      efficiency in the group with dyslexia could be explained by phonological
      awareness, the children with dyslexia were also tested on working memory. Results
      of a mediation analysis showed a significant indirect effect of working memory on
      word reading efficiency via phonological awareness. Working memory predicted
      reading efficiency, via its relation with phonological awareness in children with
      dyslexia. This indicates that working memory is necessary for word reading
      efficiency via its impact on phonological awareness and that phonological
      awareness continues to be important for word reading efficiency in older children
      with dyslexia.

PMID- 29577522
TI  - Fear of pain and cortisol reactivity predict the strength of stress-induced
      hypoalgesia.
AB  - BACKGROUND: Acute stress can have an effect on pain sensitivity, yet the
      direction of the effect - whether it is hypoalgesic or hyperalgesic - is mixed
      across studies. Moreover, which part of the stress response influences pain
      sensitivity is still unclear. In the current experimental study, we aim to
      examine the effect of acute stress on heat pain thresholds and pain tolerance
      levels in healthy participants, while taking into account individual differences
      in stress responses. METHODS: Forty-two healthy participants were randomly
      assigned to either a well-validated stress paradigm: the Maastricht Acute Stress
      Task (MAST; combining physical and psychological stressors) or to a nonstressful
      version of the task. Heat pain thresholds and tolerance levels were assessed at
      three times: prior to the MAST, immediately after the MAST during the presumed
      sympatho-adrenal medullary (SAM) response, and 15 min after MAST to cover the
      presumed hypothalamus-pituitary-adrenal (HPA) axis response. Stress responses
      were assessed both subjectively and physiologically. RESULTS: We observed that
      the acute stress induction led to increased heat pain thresholds, an effect that
      was present only in participants showing a cortisol response following stress
      induction and only in the presumed HPA axis time window. The strength of this
      hypoalgesic effect was further predicted by the change in cortisol and by fear of
      pain levels. CONCLUSIONS: Our findings indicate that the HPA axis - and not the
      autonomic - stress response specifically underlies this stress-induced
      hypoalgesic effect, having important implications for clinical states with HPA
      axis dysfunctions. SIGNIFICANCE: This experimental study shows that an acute
      stress induction - that combines physical and psychological stressors - increases
      heat pain thresholds, but not tolerance in healthy participants. Furthermore, the
      magnitude of this stress-induced hypoalgesic effect is predicted by cortisol
      reactivity and fear of pain, revealing specific involvement of the HPA axis
      stress system and interactions with pain-related psychosocial aspects.

PMID- 29577523
TI  - What's in a name? Perspectives of dyslexia assessors working with students in the
      UK higher education sector.
AB  - Research findings and positions concerning the nature of the dyslexia construct
      are currently diverse and increasingly complex. The ability of assessor
      practitioners to operationalize such knowledge and categorically diagnose
      dyslexia in any reliable and consistent way is being questioned. This study aimed
      to explore the way in which diverse and complex research findings are
      operationalized in the dyslexia diagnostic assessment of UK higher education
      students. The perspectives of 118 professional assessors of dyslexia working
      within the sector were collected using a questionnaire and some interviews. Data
      were analysed both quantitatively and qualitatively, as appropriate, and then
      integrated. The results confirmed critics' concerns about the consistency and
      reliability of the construct as currently diagnosed within the higher education
      context. Key controversial aspects of practice that emerged included the
      contextualized interpretation of literacy difficulties, a general commitment to
      discrepancy concepts, scepticism about the face validity of prescribed
      psychometric tests, and a related reliance on professional observation and
      experience above test results. The findings pointed to the need for a more
      informed nuanced understanding of the dyslexia label and a more cautious and
      responsible attitude towards its use.

PMID- 29577524
TI  - Pulmonary infarction secondary to pulmonary embolism: An evolving paradigm.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary infarction (PI) from pulmonary embolism (PE)
      remains an entity of unclear aetiology. PI has been thought to occur in elderly
      patients with cardiopulmonary disease. We hypothesize younger patients without
      cardiopulmonary comorbidities are at highest risk. Our study aims to characterize
      PI clinically and radiographically, determine associated risk factors and
      determine their clinical significance. METHODS: We conducted a single-centre
      retrospective review of 367 consecutive patients with PE. Clinical and
      radiographic data were compared between patients with and without PI using chi
      square and F-tests. Univariate and multivariate analyses were performed to
      evaluate risk factors for PI. RESULTS: PI occurred in 62 of 367 patients with
      acute PE (16.9%). Patients with PI were significantly younger (48 +/- 20.3 vs
      59.6 +/- 17.2 years, P < 0.01), with lower pulmonary embolism severity index
      (PESI) scores (73.7 +/- 38.1 vs 91.9 +/- 37.5 years, P < 0.01) and endorsed chest
      pain with significantly higher frequency (65% vs 39%, P < 0.01). There was no
      significant difference in other clinical symptoms, hospital length of stay or
      mortality between groups. Presence of radiographic cardiopulmonary disease was
      significantly lower in patients with PI (emphysema: 5% vs 22%, P = <0.01; aortic
      atherosclerosis: 23% vs 43%, P = <0.01). In multivariate analysis, age <=33 (OR
      3.5 CI: 1.37-8.95, P < 0.01), chest pain (OR 2.15 CI: 1.15-4.00, P = 0.02) and
      pleural effusion (OR 2.18 CI: 1.08-4.41, P = 0.03) increased PI risk and presence
      of emphysema decreased risk (OR 0.21 CI: 0.06-0.70, P = 0.01). CONCLUSION:
      Younger patients without cardiopulmonary comorbidities are at highest risk of PI.
      Chest pain and pleural effusion significantly increased risk of PI while presence
      of radiographic emphysema reduced risk.

PMID- 29577525
TI  - Post-hematopoietic stem cell transplant hemophagocytic lymphohistiocytosis or an
      impostor: Case report and review of literature.
AB  - HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic
      or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment
      syndrome, graft rejection/failure, acute graft-vs-host disease, infections
      systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy).
      Moreover, this period is usually marked by febrile illness, cytopenia, and a
      "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin
      and sCD25. These parameters overlap with the diagnostic criteria for HLH. Such
      confounding factors make the management of post-HSCT HLH quite challenging. We
      illustrate this critical issue with case report of a patient who was diagnosed
      with HLH after allogeneic HSCT for tAML. He received MP and CsA for HLH but VP-16
      was not administered due to fear of severe myelosuppression. Fortunately, he
      responded well to treatment and remains in remission to date. We recommend
      caution while using HLH-94/HLH-2004 guidelines for the diagnosis and management
      of post-HSCT HLH. In this article, we pinpoint these issues with a brief review
      of all the pediatric cases and clinical studies of post-HSCT HLH along with a
      critical evaluation of its various diagnostic criteria. Finally, based on the
      limitations of current diagnostic criteria, we suggest a need for formulating
      disease-specific diagnostic criteria for post-HSCT HLH.

PMID- 29577527
TI  - Endosomal sorting complexes required for ESCRTing cells toward death during
      neurogenesis, neurodevelopment and neurodegeneration.
AB  - The endosomal sorting complexes required for transport (ESCRT) proteins help in
      the recognition, sorting and degradation of ubiquitinated cargoes from the cell
      surface, long-lived proteins or aggregates, and aged organelles present in the
      cytosol. These proteins take part in the endo-lysosomal system of degradation.
      The ESCRT proteins also play an integral role in cytokinesis, viral budding and
      mRNA transport. Many neurodegenerative diseases are caused by toxic accumulation
      of cargo in the cell, which causes stress and ultimately leads to neuronal death.
      This accumulation of cargo occurs because of defects in the endo-lysosomal
      degradative pathway-loss of function of ESCRTs has been implicated in this
      mechanism. ESCRTs also take part in many survival processes, lack of which can
      culminate in neuronal cell death. While the role played by the ESCRT proteins in
      maintaining healthy neurons is known, their role in neurodegenerative diseases is
      still poorly understood. In this review, we highlight the importance of ESCRTs in
      maintaining healthy neurons and then suggest how perturbations in many of the
      survival mechanisms governed by these proteins could eventually lead to cell
      death; quite often these correlations are not so obviously laid out. Extensive
      neuronal death eventually culminates in neurodegeneration.

PMID- 29577526
TI  - Assessment of bulbar function in amyotrophic lateral sclerosis: validation of a
      self-report scale (Center for Neurologic Study Bulbar Function Scale).
AB  - BACKGROUND AND PURPOSE: Impaired bulbar functions of speech and swallowing are
      among the most serious consequences of amyotrophic lateral sclerosis (ALS).
      Despite this, clinical trials in ALS have rarely emphasized bulbar function as an
      endpoint. The rater-administered Amyotrophic Lateral Sclerosis Functional Rating
      Scale-Revised (ALSFRS-R) or various quality-of-life measures are commonly used to
      measure symptomatic benefit. Accordingly, we sought to evaluate the utility of
      measures specific to bulbar function in ALS. METHODS: We assessed bulbar
      functions in 120 patients with ALS, with clinicians first making direct
      observations of the degree of speech, swallowing and salivation impairment in
      these subjects. Clinical diagnosis of bulbar impairment was then compared with
      ALSFRS-R scores, speech rate, time to swallow liquids and solids, and scores
      obtained when patients completed visual analog scales (VASs) and the newly
      developed 21-question self-administered Center for Neurologic Study Bulbar
      Function Scale (CNS-BFS). RESULTS: The CNS-BFS, ALSFRS-R, VAS and timed speech
      and swallowing were all concordant with clinician diagnosis. The self-report CNS
      BFS and ALSFRS-R bulbar subscale best predicted clinician diagnosis with
      misclassification rates of 8% and 14% at the optimal cut-offs, respectively. In
      addition, the CNS-BFS speech and swallowing subscales outperformed both the
      bulbar component of the ALSFRS-R and speech and swallowing VASs when correlations
      were made between these scales and objective measures of timed reading and
      swallowing. CONCLUSIONS: Based on these findings and its relative ease of
      administration, we conclude that the CNS-BFS is a useful metric for assessing
      bulbar function in patients with ALS.

PMID- 29577528
TI  - Differential effect of drought regimes on the seedling performance of six
      floodplain grassland species.
AB  - The performance of seedlings is crucial for the survival and persistence of plant
      populations. Although drought frequently occurs in floodplains and can cause
      seedling mortality, studies on the effects of drought on seedlings of floodplain
      grasslands are scarce. We tested the hypotheses that drought reduces aboveground
      biomass, total biomass, plant height, number of leaves, leaf area and specific
      leaf area (SLA), and increases root biomass and root-mass fraction (RMF) and that
      seedlings from species of wet floodplain grasslands are more affected by drought
      than species of dry grasslands. In a greenhouse study, we exposed seedlings of
      three confamilial pairs of species (Pimpinella saxifraga, Selinum carvifolia,
      Veronica teucrium, Veronica maritima, Sanguisorba minor, Sanguisorba officinalis)
      to increasing drought treatments. Within each plant family, one species is
      characteristic of wet and one of dry floodplain grasslands, confamilial in order
      to avoid phylogenetic bias of the results. In accordance with our hypotheses,
      drought conditions reduced aboveground biomass, total biomass, plant height,
      number of leaves and leaf area. Contrary to our hypotheses, drought conditions
      increased SLA and decreased root biomass and RMF of seedlings. Beyond the effects
      of the families, the results were species-specific (V. maritima being the most
      sensitive species) and habitat-specific. Species indicative of wet floodplain
      grasslands appear to be more sensitive to drought than species indicative of dry
      grasslands. Because of species- and habitat-specific responses to reduced water
      availability, future drought periods due to climate change may severely affect
      some species from dry and wet habitats, while others may be unaffected.

PMID- 29577529
TI  - Quality of life in children with developmental language disorder.
AB  - BACKGROUND: Developmental language disorder (DLD) is common in children, but
      little is known about its association with quality of life (QoL) in middle
      childhood. QoL is a complex construct, aligning with an individual's sense of
      well-being and is related to functional limitations associated with DLD.
      Biopsychosocial models of disability account for both the extent and functional
      limitations of the impairment; however, the DLD literature rarely reports on both
      aspects. Studies are required that detail QoL in children with and without DLD.
      AIMS: To investigate the association between DLD, identified at 4 years and
      persisting at 7 years, and QoL over 4, 7 and 9 years; to compare QoL for children
      whose DLD was mild to moderate and severe at 7 years; and to investigate how
      variables known to impact on language development (e.g., maternal vocabulary), as
      well as social-emotional behaviours at 4 and 7 years contribute to QoL at 9
      years. METHODS & PROCEDURES: The analyses included 872 children who participated
      in the 4-, 7- and 9-year data collection of the Early Language in Victoria Study
      (ELVS). We compared the parent-reported QoL profiles at 4, 7 and 9 years for
      children with and without DLD, and those with mild to moderate and severe DLD
      using the Pediatric Quality of Life Inventory (PedsQL). We conducted regression
      analyses to estimate how child, family and environmental factors predicted QoL at
      9 years, including social-emotional behaviours measured using the Strengths &
      Difficulties Questionnaire (SDQ) at 4 and 7 years. OUTCOME & RESULTS: Children
      with DLD (n = 70) had lower parent-reported QoL at 9 years than typically
      developing children (n = 802), with mean scores of 74.9 and 83.9 respectively.
      There was no evidence of differences in QoL between those with severe (n = 14) or
      mild to moderate (n = 56) DLD. In contrast to their peers, children with DLD had
      a profile of declining QoL between 4 and 9 years. For all children, language
      skills at 7 years predicted QoL at 9 years. For children with DLD, emotional
      symptoms and peer problems at 4 years plus SDQ Total Difficulties at 7 years were
      predictive of lower QoL at 9 years. CONCLUSIONS & IMPLICATIONS: Children with DLD
      had a lower QoL than their typical peers at 9 years and, contrary to previous
      studies, differences in QoL were not observed with DLD severity. Co-occurring
      social-emotional problems appear to play an important role in contributing to the
      lower QoL experienced by children with DLD. Consideration of associated
      functional limitations is required to support the communication and social
      development of all young children with DLD.

PMID- 29577530
TI  - Induction of Signal Transduction by Using Non-Channelrhodopsin-Type Optogenetic
      Tools.
AB  - Signal transductions are the basis for all cellular functions. Previous studies
      investigating signal transductions mainly relied on pharmacological inhibition,
      RNA interference, and constitutive active/dominant negative protein expression
      systems. However, such studies do not allow the modulation of protein activity
      with high spatial and temporal precision in cells, tissues, and organs in
      animals. Recently, non-channelrhodopsin-type optogenetic tools for regulating
      signal transduction have emerged. These photoswitches address several
      disadvantages of previous techniques, and allow us to control a variety of signal
      transductions such as cell membrane dynamics, calcium signaling, lipid signaling,
      and apoptosis. In this review we summarize recent advances in the development of
      such photoswitches and in how these optotools are applied to signaling processes.

PMID- 29577531
TI  - Burden of illness and costs among paediatric haemophilia patients with and
      without central venous access devices treated in US hospitals.
AB  - INTRODUCTION: Central venous access devices (CVADs) facilitate repeated or urgent
      treatments for paediatric haemophilia patients, but are associated with
      complications. This study examined the burden of illness, healthcare utilization
      and costs for CVADs in a real-world hospital setting. MATERIALS AND METHODS: This
      study included haemophilia patients ages <=18 years with discharges during 2006
      2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD
      9 diagnosis codes and CVAD exposure using billing information. After matching
      haemophilia patients with and without CVADs on demographic and clinical
      characteristics, we compared infection, thrombosis, length of stay (LOS),
      inflation-adjusted hospital cost (2014 $USD) and readmission outcomes using
      generalized estimating equation models adjusted for hospital teaching status.
      RESULTS: Among 4793 paediatric haemophilia patients treated at one of 548
      hospitals, a total of 197 patients were identified with CVAD exposure. The
      matched sample included 310 haemophilia patients (155 CVAD and 155 non-CVAD).
      CVAD cases had greater frequencies of all-cause infections (29% vs 17%, P = .01)
      and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P
      = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs
      $25389, P = .02) as well as more inpatient and outpatient visits at 30-, 60- and
      90-days (P < .05 for all differences) compared with non-CVAD patients.
      CONCLUSION: Paediatric haemophilia patients with CVADs experienced greater
      infection rates, healthcare utilization and higher hospitalization costs compared
      with non-CVAD patients. The results of this study may inform further research
      efforts to understand the costs and benefits of novel treatment alternatives for
      young haemophilia patients requiring CVADs.

PMID- 29577532
TI  - Singly and Doubly 1,2-Phenylene-Inserted Porphyrin Arch-Tape Dimers: Synthesis
      and Highly Contorted Structures.
AB  - Singly and doubly 1,2-phenylene-inserted NiII porphyrin arch-tape dimers 3 and 9
      were synthesized from the corresponding beta-to-beta 1,2-phenylene-bridged NiII
      porphyrin dimers 5 and 11 via Ni0 -mediated reductive cyclization and
      DDQ/Sc(OTf)3 -promoted oxidative cyclization as key steps, respectively. Owing to
      the fused eight-membered ring(s), 3 showed a more contorted structure than those
      of previously reported arch-tape dimers 2 a and 2 b possessing a fused seven
      membered ring. Furthermore, 9 displayed much larger molecular contortion. As the
      molecular contortion increases, the Q band of the absorption spectrum becomes
      more red-shifted and the electrochemcial HOMO-LUMO gap becomes smaller, reaching
      at 1294 nm and 0.77 eV in 9, respectively. The effect of molecular contortion on
      the electronic properties was studied by means of DFT calculations.

PMID- 29577533
TI  - Local Atomic Arrangements and Band Structure of Boron Carbide.
AB  - Boron carbide, the simple chemical combination of boron and carbon, is one of the
      best-known binary ceramic materials. Despite that, a coherent description of its
      crystal structure and physical properties resembles one of the most challenging
      problems in materials science. By combining ab initio computational studies,
      precise crystal structure determination from diffraction experiments, and state
      of-the-art high-resolution transmission electron microscopy imaging, this
      concerted investigation reveals hitherto unknown local structure modifications
      together with the known structural alterations. The mixture of different local
      atomic arrangements within the real crystal structure reduces the electron
      deficiency of the pristine structure CBC+B12 , answering the question about
      electron precise character of boron carbide and introducing new electronic states
      within the band gap, which allow a better understanding of physical properties.

PMID- 29577534
TI  - Transition-Metal-Free Decarboxylative Propargylic Substitution/Cyclization with
      either Azolium Enolates or Acyl Anions.
AB  - Presented herein is an unprecedented transition-metal-free propargylic
      substitution reaction with either azolium enolates or acyl anions, which are
      generated from aldehydes under N-heterocyclic carbene catalysis. This new
      catalytic activation operates on readily available cyclic propargylic carbamates
      through decarboxylation, and generates reactive allene intermediates that can
      undergo divergent cyclization pathways to deliver skeletally diverse polycyclic
      compounds with high levels of efficiency and excellent enantioselectivities.

PMID- 29577535
TI  - A [RuRu] Analogue of an [FeFe]-Hydrogenase Traps the Key Hydride Intermediate of
      the Catalytic Cycle.
AB  - The active site of the [FeFe]-hydrogenases features a binuclear [2Fe]H sub
      cluster that contains a unique bridging amine moiety close to an exposed iron
      center. Heterolytic splitting of H2 results in the formation of a transient
      terminal hydride at this iron site, which, however is difficult to stabilize. We
      show that the hydride intermediate forms immediately when [2Fe]H is replaced with
      [2Ru]H analogues through artificial maturation. Outside the protein, the [2Ru]H
      analogues form bridging hydrides, which rearrange to terminal hydrides after
      insertion into the apo-protein. H/D exchange of the hydride only occurs for
      [2Ru]H analogues containing the bridging amine moiety.

PMID- 29577537
TI  - Peer work in Open Dialogue: A discussion paper.
AB  - Open Dialogue is a resource-oriented approach to mental health care that
      originated in Finland. As Open Dialogue has been adopted across diverse
      international healthcare settings, it has been adapted according to contextual
      factors. One important development in Open Dialogue has been the incorporation of
      paid, formal peer work. Peer work draws on the knowledge and wisdom gained
      through lived experience of distress and hardship to establish mutual,
      reciprocal, and supportive relationships with service users. As Open Dialogue is
      now being implemented across mental health services in Australia, stakeholders
      are beginning to consider the role that peer workers might have in this model of
      care. Open Dialogue was not, initially, conceived to include a specific role for
      peers, and there is little available literature, and even less empirical
      research, in this area. This discussion paper aims to surface some of the current
      debates and ideas about peer work in Open Dialogue. Examples and models of peer
      work in Open Dialogue are examined, and the potential benefits and challenges of
      adopting this approach in health services are discussed. Peer work in Open
      Dialogue could potentially foster democracy and disrupt clinical hierarchies, but
      could also move peer work from reciprocal to a less symmetrical relationship of
      'giver' and 'receiver' of care. Other models of care, such as lived experience
      practitioners in Open Dialogue, can be conceived. However, it remains uncertain
      whether the hierarchical structures in healthcare and current models of funding
      would support any such models.

PMID- 29577536
TI  - Hypoglycaemia incidence and recovery during home use of hybrid closed-loop
      insulin delivery in adults with type 1 diabetes.
AB  - Glucose excursion was assessed prior to and post hypoglycaemia to increase
      understanding of hypoglycaemia incidence and recovery during hybrid closed-loop
      insulin delivery. We retrospectively analysed data from 60 adults with type 1
      diabetes who received, in a crossover randomized design, day-and-night hybrid
      closed-loop insulin delivery and insulin pump therapy, the latter with or without
      real-time continuous glucose monitoring. Over 4-week study periods, we identified
      hypoglycaemic episodes, defined as sensor glucose <3.0 mmol/L, and analysed
      sensor glucose relative to the onset of hypoglycaemia. We identified 377
      hypoglycaemic episodes during hybrid closed-loop intervention vs 662 during
      control intervention (P < .001), with a predominant reduction of nocturnal
      hypoglycaemia. The slope of sensor glucose prior to hypoglycaemia was steeper
      during closed-loop intervention than during control intervention (P < .01), while
      insulin delivery was reduced (P < .01). During both day and night, participants
      recovered from hypoglycaemia faster when treated by closed-loop intervention. At
      120 minutes post hypoglycaemia, sensor glucose levels were higher during closed
      loop intervention compared to the control period (P < .05). In conclusion, closed
      loop intervention reduces the risk of hypoglycaemia, particularly overnight, with
      swift recovery from hypoglycaemia leading to higher 2-hour post-hypoglycaemia
      glucose levels.

PMID- 29577539
TI  - The prognosis for glycemic status among children and youth with obesity 2 years
      after entering a weight management program.
AB  - BACKGROUND: To address gaps in knowledge of the longitudinal trajectory of
      dysglycemia in children with obesity, this study aimed to: (1) describe the
      changes in glycemic status over 2 years; (2) establish a predictive model for
      development of prediabetes among children with euglycemia; and (3) evaluate the
      influence of change in body mass index (BMI) z-score on glycemic status. METHODS:
      Children aged 5 to 17 years entered this prospective, longitudinal study at the
      time of entry to a weight management program. Measures included a 75-g oral
      glucose tolerance test (OGTT), fasting blood glucose, hemoglobin A1c (HbA1c),
      lipid profile, liver enzymes and anthropometric measures at baseline, 1 and 2
      years. Cox proportional hazard was used to build a predictive model for
      prediabetes. RESULTS: The cohort included 270 children, mean age: 11.6 +/- 2.7
      years and BMI z-score: 3.1. The baseline prevalence of prediabetes, based upon
      elevated 2-hour glucose in OGTT or HbA1c, was 100/270 (37.0%). Among children
      with prediabetes at baseline, 53 (53.0%) continued to have prediabetes over the
      following 2 years, 15 (15.0%) were euglycemic at 1 year and had prediabetes at 2
      years, 20 (20.0%) became euglycemic and remained so. Change in BMI z-score
      predicted dysglycemic status at 2 years. Among those euglycemic at baseline, the
      incidence of prediabetes was 14 (8.2%) after 1 year, 20 (12.8%) at 2 years.
      Predictors of incident prediabetes were baseline BMI z-score; hazard ratio (HR):
      1.72, 95th confidence interval (CI: 1.08, 2.74) and baseline HbA1c HR: 1.26, 95th
      CI (1.02-1.56) when controlling for age, family history of diabetes and sex.
      CONCLUSION: Prediabetes presents significant morbidity in children with obesity.
      Family-based lifestyle interventions might delay prediabetes progression.

PMID- 29577538
TI  - Family adjustment to diabetes diagnosis in children: Can participation in a study
      on type 1 diabetes genetic risk be helpful?
AB  - BACKGROUND: Diagnosis of type 1 diabetes often causes a negative psychological
      impact on families. We examined whether parents and children enrolled in The
      Environmental Determinants of Diabetes in the Young (TEDDY) study differ in their
      psychological adjustment to diabetes diagnosis compared to children diagnosed
      with diabetes in the community. METHODS: TEDDY follows 8676 children at genetic
      risk for type 1 diabetes from birth. Fifty-four TEDDY children diagnosed with
      diabetes and 54 age-matched community control children diagnosed with diabetes
      were enrolled. Participants were aged 3 to 10 years and study visits occurred at
      3, 6, and 12 months postdiagnosis. Psychological measures included an adapted
      diabetes-specific State Anxiety Inventory, the Pediatric Quality of Life
      Inventory-Diabetes Module, and the Pediatric Inventory for Parents, which
      measures frequency and difficulty of parenting stress. RESULTS: A generalized
      estimating equation analysis based on a difference score between TEDDY children
      and community controls found no significant differences between TEDDY parents and
      community controls on parent diabetes-specific anxiety (P = .30). However, TEDDY
      children exhibited better diabetes-specific quality of life (P = .03) and TEDDY
      parents reported lower frequency (P = .004) and difficulty (P = .008) of
      parenting stress compared to community controls. CONCLUSIONS: Children diagnosed
      with at-risk for type 1 diabetes who have previously enrolled in research
      monitoring have improved diabetes quality of life and lower parenting stress
      postdiagnosis compared to children diagnosed in the community. Families in follow
      up studies may be more prepared if their child is diagnosed with diabetes.

PMID- 29577540
TI  - Burden of cardio-renal-metabolic conditions in adults with type 2 diabetes within
      the Diabetes Collaborative Registry.
AB  - We examined the prevalence of cardio-renal-metabolic (CaReMe) conditions and
      their combinations among 530 747 adults with type 2 diabetes in a USA-based
      outpatient registry of 271 primary care, cardiology and endocrinology offices. We
      evaluated the following CaReMe conditions: hypertension, hyperlipidaemia,
      coronary artery disease (CAD), chronic kidney disease (CKD), cerebrovascular
      disease, peripheral artery disease, atrial fibrillation, heart failure, and gout
      or hyperuricaemia; prevalence estimates were adjusted based on the distribution
      of diabetes by age in the US population in 2015. We found that it was uncommon
      for patients to have isolated type 2 diabetes without other CaReMe conditions,
      with only 6.4% having no other CaReMe conditions and 51% having >=3 other CaReMe
      conditions. The most prevalent individual conditions were hypertension (83%),
      hyperlipidemia (81%), CAD (32%) and CKD (20%), and the most common combinations
      included various groupings of hypertension, hyperlipidaemia, atherosclerotic
      cardiovascular disease and CKD. Older age, male sex and tobacco use were each
      associated with increased numbers of CaReMe conditions. These findings highlight
      the clinical need for novel treatment strategies for diabetes that address both
      glycaemia and coexisting disease states.

PMID- 29577541
TI  - Prognostic value of inferior mesenteric artery lymph node metastasis in cancer of
      the descending colon, sigmoid colon and rectum.
AB  - AIM: This study aimed to analyse the potential significance of metastasis to the
      inferior mesenteric artery lymph node (IMA-LN) in patients with malignancy of the
      left colon and rectum. METHOD: A retrospective analysis of a cohort of 890
      patients collected prospectively who underwent radical resection of a primary
      tumour of the descending colon, sigmoid colon and rectum in our department from 1
      January 2009 to 31 December 2015 was performed. Patients were divided into an IMA
      LN metastasis (IMA-LN (+)) group (n = 51) and a non IMA-LN metastasis (IMA-LN (
      )) group (n = 839). A total of 801 patients were followed by a designated member
      of the study staff. Clinical features, pathological characteristics, recurrence
      patterns and survival rates were compared between the two groups. RESULTS: In the
      IMA-LN (+) group, the risk ratio of overall recurrence and tumour related death
      was 7.786 (95% CI 4.142-14.637) and 7.756 (95% CI 4.142-14.525) respectively.
      Significant differences were found in overall survival (log-rank: chi2  = 69.06,
      P < 0.0001) and disease-free survival (log-rank: chi2  = 69.06, P < 0.0001)
      between the two groups. Furthermore, there were significant differences in
      overall survival (log-rank: chi2  = 18.47, P < 0.0001) and disease-free survival
      (log-rank: chi2  = 16.99, P < 0.0001) between the IMA-LN (-) and IMA-LN (+)
      subgroups of patients with Stage N2 disease. Multivariate survival analysis
      indicated that IMA-LN (+) was an independent risk factor of poor prognosis. There
      was no difference in the prognosis between high tie and low tie with IMA-LN
      dissection. CONCLUSION: Inferior mesenteric artery lymph node metastasis was an
      independent predictive factor for high systemic recurrence. Low ligation of the
      IMA with IMA-LN dissection was not inferior to high ligation.

PMID- 29577543
TI  - A Forkhead Box Protein C2 Inhibitor: Targeting Epithelial-Mesenchymal Transition
      and Cancer Metastasis.
AB  - The epithelial-mesenchymal transition (EMT) has been suggested as a new target
      for therapeutic intervention of metastatic cancer. Forkhead box protein C2
      (FOXC2) is known to be necessary for initiating and maintaining EMT, and
      therefore bestows on cancer cells metastatic and cancer stem cell (CSC)-like
      phenotypes, allowing cells to acquire higher motility, invasiveness, self
      renewal, and therapy resistance. Here, we describe the first inhibitor of FOXC2,
      MC-1-F2. MC-1-F2 was able to induce cadherin switching and reverse EMT through
      the degradation of FOXC2 and blocking of its nuclear localization. In addition,
      MC-1-F2 was very effective in inhibiting cancer cell migration and invasion. As
      the first small-molecule inhibitor of FOXC2 and the first compound targeting EMT
      associated transcription factor, MC-1-F2 will pave the way for a new anticancer
      therapeutic agent targeting metastatic cancer and help to elucidate the network
      of EMT signaling pathways.

PMID- 29577542
TI  - Further analysis of barley MORC1 using a highly efficient RNA-guided Cas9 gene
      editing system.
AB  - Microrchidia (MORC) proteins comprise a family of proteins that have been
      identified in prokaryotes and eukaryotes. They are defined by two hallmark
      domains: a GHKL-type ATPase and an S5-fold. In plants, MORC proteins were first
      discovered in a genetic screen for Arabidopsis thaliana mutants compromised for
      resistance to a viral pathogen. Subsequent studies expanded their role in plant
      immunity and revealed their involvement in gene silencing and genome
      stabilization. Little is known about the role of MORC proteins of cereals,
      especially because knockout (KO) mutants were not available and assessment of
      loss of function relied only on RNAi strategies, which were arguable, given that
      MORC proteins in itself are influencing gene silencing. Here, we used a
      Streptococcus pyogenes Cas9 (SpCas9)-mediated KO strategy to functionally study
      HvMORC1, one of the current seven MORC members of barley. Using a novel barley
      RNA Pol III-dependent U3 small nuclear RNA (snRNA) promoter to drive expression
      of the synthetic single guide RNA (sgRNA), we achieved a very high mutation
      frequency in HvMORC1. High frequencies of mutations were detectable by target
      sequencing in the callus, the T0 generation (77%) and T1 generation (70%-100%),
      which constitutes an important improvement of the gene-editing technology in
      cereals. Corroborating and extending earlier findings, SpCas9-edited hvmorc1-KO
      barley, in clear contrast to Arabidopsis atmorc1 mutants, had a distinct
      phenotype of increased disease resistance to fungal pathogens, while morc1
      mutants of either plant showed de-repressed expression of transposable elements
      (TEs), substantiating that plant MORC proteins contribute to genome stabilization
      in monocotyledonous and dicotyledonous plants.

PMID- 29577544
TI  - Interpersonal relationships and communication as a gateway to patient and public
      involvement and engagement.

PMID- 29577545
TI  - Efficient genome editing of wild strawberry genes, vector development and
      validation.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9
      system is an effective genome editing tool for plant and animal genomes. However,
      there are still few reports on the successful application of CRISPR-Cas9 to
      horticultural plants, especially with regard to germ-line transmission of
      targeted mutations. Here, we report high-efficiency genome editing in the wild
      strawberry Fragaria vesca and its successful application to mutate the auxin
      biosynthesis gene TAA1 and auxin response factor 8 (ARF8). In our CRISPR system,
      the Arabidopsis U6 promoter AtU6-26 and the wild strawberry U6 promoter FveU6-2
      were each used to drive the expression of sgRNA, and both promoters were shown to
      lead to high-efficiency genome editing in strawberry. To test germ-line
      transmission of the edited mutations and new mutations induced in the next
      generation, the progeny of the primary (T0) transgenic plants carrying the CRISPR
      construct was analysed. New mutations were detected in the progeny plants at a
      high efficiency, including large deletions between the two PAM sites. Further, T1
      plants harbouring arf8 homozygous knockout mutations grew considerably faster
      than wild-type plants. The results indicate that our CRISPR vectors can be used
      to edit the wild strawberry genome at a high efficiency and that both sgRNA
      design and appropriate U6 promoters contribute to the success of genomic editing.
      Our results open up exciting opportunities for engineering strawberry and related
      horticultural crops to improve traits of economic importance.

PMID- 29577546
TI  - Thesium linophyllon parasitizes and suppresses expansive Calamagrostis epigejos.
AB  - Root-hemiparasitic interaction between the dominant grass Calamagrostis epigejos
      and the hemiparasite Thesium linophyllon was studied to assess the potential of
      the parasite to regulate dominance of the grass, which is expanding into species
      rich steppe grasslands. First, we aimed to identify physiological links between
      the two species as a principal indicator of the parasitic relationship. Second,
      we analysed the dynamics of the two species in the vegetation of a steppe
      grassland at the foot of the Bukk Mountains, Hungary, where their joint presence
      is recorded in a long-term permanent plot monitoring dataset to detect patterns
      associated with the parasitic ecological interaction. Numerous well-developed
      functional haustoria of Th. linophyllon were identified on the root systems of C.
      epigejos. The joint dynamics of C. epigejos and Th. linophyllon displayed clear
      signs of the parasitic interaction: (1) the dynamics of Th. linophyllon frequency
      was positively associated with the initial cover of C. epigejos; (2) maximum
      recorded cover values of the two species were strongly positively correlated; and
      (3) the extent of C. epigejos decrease in the vegetation was significantly
      positively associated with maximum Th. linophyllon cover recorded throughout the
      monitoring period. We demonstrate that C. epigejos can be parasitized by Th.
      linophyllon, which restricts abundance of the grass. Th. linophyllon thus has
      potential to act as a native biological control of C. epigejos in steppe
      grasslands.

PMID- 29577548
TI  - Developing an adherence in hypertension questionnaire short version: MUAH-16
      statistical and methodological issues.

PMID- 29577547
TI  - Transgenic expression of plastidic glutamine synthetase increases nitrogen uptake
      and yield in wheat.
AB  - The plastidic glutamine synthetase isoform (GS2) plays a key role in nitrogen (N)
      assimilation. We introduced TaGS2-2Abpro::TaGS2-2Ab, the favourable allele of
      TaGS2-2A in the winter wheat (Triticum aestivum) variety Ji5265. Transgenic
      expression of TaGS2-2Ab significantly increased GS2 abundance and GS activity in
      leaves. Two consecutive field experiments showed the transgenic lines had higher
      grain yield, spike number, grain number per spike and 1000-grain weight than did
      the wild type under both low N and high N conditions. Analysis of N use-related
      traits showed that transgenic expression of TaGS2-2Ab increased root ability to
      acquire N, N uptake before and after flowering, remobilization of N to grains and
      N harvest index. Measurement of chlorophyll content and net photosynthesis rate
      in flag leaves during grain filling stage revealed that the transgenic lines had
      prolonged leaf functional duration as compared with the wild type. These results
      suggest that TaGS2 plays important role in N use, and the favourable allele TaGS2
      2Ab is valuable in engineering wheat with improved N use efficiency and grain
      yield.

PMID- 29577549
TI  - What the ~1.4 Ga Xiamaling Formation can and cannot tell us about the mid
      Proterozoic ocean.
AB  - Despite a surge of recent work, the evolution of mid-Proterozoic oceanic
      atmospheric redox remains heavily debated. Constraining the dynamics of
      Proterozoic redox evolution is essential to determine the role, if any, that
      anoxia played in protracting the development of eukaryotic diversity. We present
      a multiproxy suite of high-resolution geochemical measurements from a drill core
      capturing the ~1.4 Ga Xiamaling Formation, North China Craton. Specifically, we
      analyzed major and trace element concentrations, sulfur and molybdenum isotopes,
      and iron speciation not only to better understand the local redox conditions but
      also to establish how relevant our data are to understanding the contemporaneous
      global ocean. Our results suggest that throughout deposition of the Xiamaling
      Formation, the basin experienced varying degrees of isolation from the global
      ocean. During deposition of the lower organic-rich shales (130-85 m depth), the
      basin was extremely restricted, and the reservoirs of sulfate and trace metals
      were drawn down almost completely. Above a depth of 85 m, shales were deposited
      in dominantly euxinic waters that more closely resembled a marine system and thus
      potentially bear signatures of coeval seawater. In the most highly enriched
      sample from this upper interval, the concentration of molybdenum is 51 ppm with a
      delta98 Mo value of +1.70/00. Concentrations of Mo and other redox-sensitive
      elements in our samples are consistent with a deep ocean that was largely anoxic
      on a global scale. Our maximum delta98 Mo value, in contrast, is high compared to
      published mid-Proterozoic data. This high value raises the possibility that the
      Earth's surface environments were transiently more oxygenated at ~1.4 Ga compared
      to preceding or postdating times. More broadly, this study demonstrates the
      importance of integrating all available data when attempting to reconstruct
      surface O2 dynamics based on rocks of any age.

PMID- 29577550
TI  - Single and multiple dose evaluation of a novel MetAP2 inhibitor: Results of a
      randomized, double-blind, placebo-controlled clinical trial.
AB  - AIMS: Methionine aminopeptidase 2 (MetAP2) inhibition has been shown to result in
      significant weight loss and improved glucose control. This Phase 1 clinical trial
      assessed the safety and tolerability, pharmacokinetics and preliminary efficacy
      of a novel MetAP2 inhibitor, ZGN-1061. METHODS: This clinical trial included a
      single ascending dose (SAD) phase in healthy subjects (BMI, 23 to <30 kg/m2 ) and
      a multiple ascending dose (MAD) phase in otherwise healthy subjects (BMI, 27 to
      40 kg/m2 ). SAD phase doses, administered subcutaneously (SC), were 0.2, 0.6,
      1.2, 2.4, 3.6 and 4.8 mg and the MAD phase evaluated doses of 0.2, 0.6 and 1.8 mg
      twice weekly SC for 4 weeks. RESULTS: The SAD phase included 39 subjects (ZGN
      1061, N = 28; placebo, N = 11); 90% were male and BMI was 26.4 kg/m2 . ZGN-1061
      was well tolerated across all doses, with the most frequent adverse events being
      mild headache and procedural-related irritation. There were no severe or serious
      adverse events. All doses of ZGN-1061 were rapidly absorbed and cleared,
      resulting in short duration of exposure that is anticipated to minimize potential
      off-drug target risks. The MAD phase included 29 subjects (ZGN-1061, N = 22;
      placebo, N = 7); 76% were male and BMI was 33.5 kg/m2 . Safety observations were
      consistent with SAD findings. Efficacy measures in the MAD phase indicated trends
      for weight change (-1.5 kg total ZGN-1061 vs -0.2 kg placebo) and other biomarker
      changes. CONCLUSIONS: ZGN-1061 was well tolerated with no safety signals in all
      doses tested. In addition, the desired pharmacokinetic profile and preliminary
      efficacy observations with ZGN-1061 support evaluation in larger and longer
      clinical trials.

PMID- 29577551
TI  - Edge fires drive the shape and stability of tropical forests.
AB  - In tropical regions, fires propagate readily in grasslands but typically consume
      only edges of forest patches. Thus, forest patches grow due to tree propagation
      and shrink by fires in surrounding grasslands. The interplay between these
      competing edge effects is unknown, but critical in determining the shape and
      stability of individual forest patches, as well the landscape-level spatial
      distribution and stability of forests. We analyze high-resolution remote-sensing
      data from protected Brazilian Cerrado areas and find that forest shapes obey a
      robust perimeter-area scaling relation across climatic zones. We explain this
      scaling by introducing a heterogeneous fire propagation model of tropical forest
      grassland ecotones. Deviations from this perimeter-area relation determine the
      stability of individual forest patches. At a larger scale, our model predicts
      that the relative rates of tree growth due to propagative expansion and long
      distance seed dispersal determine whether collapse of regional-scale tree cover
      is continuous or discontinuous as fire frequency changes.

PMID- 29577552
TI  - 'It was riotous behaviour!': Mothers' experiences of adolescents' conduct while
      abusing drugs.
AB  - The impact of adolescent substance abuse is widespread and significantly
      compromises the psychosocial well-being of those closest to the adolescent. This
      is evidentially so for parents who are required to cope with the adolescent's
      misconduct. Using an interpretative phenomenological methodology, this article
      describes mothers' experiences of living with an adolescent who is dependent on
      drugs. Specifically, the article explores the mothers' accounts of the pernicious
      behaviours that the adolescents engage(d) in during their drug abuse period.
      Qualitative 1:1 interviews revealed two common forms of adolescent misconduct
      that the mothers had to contend with which were 'belligerent attitudes and
      conducts' and 'pilfering behaviours'. The mothers further reported that the
      adolescents' behaviours negatively impacted on the mother-adolescent
      relationship, producing feelings of mistrust and a lack of trust. The findings
      contribute to the sparse literature on parents' experiences and thus hold
      implications for research and practice. Understanding the challenges that mothers
      contend with when adolescents engage in problematic drug use is important for the
      development of support interventions to help parents cope effectively. Further
      implications are presented in the article.

PMID- 29577553
TI  - Metformin's impact on statin-associated muscle symptoms: An analysis of ACCORD
      study data and research materials from the NHLBI Biologic Specimen and Data
      Repository Information Coordinating Center.
AB  - Statins are widely prescribed, yet statin muscle pain limits their use, leading
      to increased cardiovascular risk. No validated therapy for statin muscle pain
      exists. The goal of the study was to assess whether metformin was associated with
      reduced muscle pain. A secondary analysis of data from the ACCORD trial was
      performed. An ACCORD sub-study assessed patients for muscle cramps and leg/calve
      pain while walking, typical non-severe statin muscle pain symptoms. We compared
      muscle pain between patients using a statin (n = 445) or both a statin and
      metformin (n = 869) at baseline. Overall patient characteristics were balanced
      between groups. Unadjusted analysis showed fewer reports of muscle cramps (35%)
      and leg/calve pain while walking (40%) with statins and metformin compared to
      statin only (muscle cramps, 42%; leg/calve pain while walking, 47%).
      Multivariable regression demonstrated a 22% odds reduction for muscle cramps (P =
      0.049) and a 29% odds reduction for leg/calve pain while walking (P = 0.01).
      Metformin appears to reduce the risk of non-severe statin muscle pain and
      additional research is needed to confirm the findings and assess metformin's
      impact on statin adherence and related cardiovascular outcomes.

PMID- 29577554
TI  - Germline and somatic genetic testing in ovarian cancer patients.

PMID- 29577555
TI  - Transanal endoscopic surgery is effective and safe after endoscopic polypectomy
      of potentially malignant rectal polyps with questionable margins.
AB  - AIM: To determine the percentage of residual lesion observed in the pathology
      study of transanal endoscopic surgery (TEM) specimens after endoscopic
      polypectomy of malignant rectal polyps with questionable margins, and the need
      for further surgery. Secondary aims: to determine the morbidity and mortality
      associated with this procedure and to identify the percentage of recurrence after
      excision by TEM. METHODS: Observational study with prospective data collection of
      all patients undergoing TEM after endoscopic polypectomy for malignant rectal
      polyps or non-invasive high-grade neoplasia, from January 2004 to December 2016.
      An en bloc full-thickness wall excision of the scar was performed. Variables
      recorded: histology of TEM specimen, 30-day morbidity and mortality according to
      the Clavien-Dindo classification, need for salvage surgery and recurrence.
      RESULTS: Fifty out of 690 patients undergoing TEM during the study period (36
      adenocarcinomas, five non-invasive high-grade neoplasias and 9 neuroendocrine
      tumors) were included. Post-surgery histology showed residual lesion in 21 (42%)
      patients: 7 neuroendocrine tumors, 10 adenomas and 4 adenocarcinomas (two pT1,
      one pT2 and one pT3). The pT2 and pT3 patients (4%) underwent salvage surgery. No
      recurrence was observed, and mean follow-up was 29.1A +/- 21.6 months. The 30-day
      morbidity rate was 14%, but 4/7 with Clavien-Dindo grade I. CONCLUSIONS: After
      endoscopic polypectomy of malignant rectal polyps with questionable margins, the
      presence of residual lesion in the pathology study of transanal resection
      specimens is high. TEM with full-thickness resection of these lesions is an
      appropriate treatment, allowing disease control and achieving minimal morbidity.

PMID- 29577556
TI  - The effect of increasing body mass index on laparoscopic surgery for colon and
      rectal cancer.
AB  - AIM: Obesity is common in Western countries and its prevalence is increasing.
      Colorectal cancer is common, and surgery for colorectal cancer is technically
      more challenging in obese patients. Laparoscopic surgery for colon cancer has
      been shown to be oncologically equivalent, with improved short- term outcomes.
      Laparoscopic surgery for rectal cancer has proven technically challenging, and
      recent results have raised concerns about oncological equivalence. Our aim was to
      evaluate the effect of body mass index (BMI) on the clinical and oncological
      outcomes of surgery for colorectal cancer, including the rate at which
      laparoscopic surgery is attempted and the rate at which laparoscopic surgery is
      converted to open surgery. METHOD: A retrospective analysis of prospectively
      collected data from two tertiary institutions was performed. Data were obtained
      from the Cabrini Monash University colorectal neoplasia database for patients
      having surgical resection for colon and rectal cancers between 1 January 2010 and
      30 June 2015. Surgical and medical complications, tumour recurrence and overall
      survival and laparoscopic surgery and conversion rates were investigated.
      RESULTS: This large case series of 1464 patients undergoing elective surgery for
      colorectal cancer has demonstrated that an elevated BMI is associated with a
      lower likelihood of attempting laparoscopic surgery and a higher conversion rate
      to open surgery when laparoscopy is attempted. Conversion was 1.9 times more
      likely in obese patients with colon cancer and 4.1 times more likely in obese
      patients with rectal cancer. The critical BMI for colon cancer patients was > 35
      kg/m2 , and for rectal cancer patients > 30 kg/m2 . Obesity is also associated
      with increased rates of surgical complications, including anastomotic leakage and
      wound complications. Pathological parameters, tumour recurrence and survival were
      not affected by elevated BMI. CONCLUSION: In the surgical management of
      colorectal cancer, obesity is associated with a lower likelihood of laparoscopic
      surgery being attempted, a higher likelihood of conversion to open surgery when
      laparoscopic surgery is attempted, and a higher rate of surgical complications.

PMID- 29577557
TI  - Myeloperoxidase, superoxide dismutase-3, cardiometabolic risk factors, and distal
      sensorimotor polyneuropathy: The KORA F4/FF4 study.
AB  - BACKGROUND: Oxidative stress has been proposed as important pathomechanism of
      cardiometabolic diseases and distal sensorimotor polyneuropathy (DSPN). However,
      the relevance of biomarkers of oxidative stress has not been investigated in this
      context. Therefore, this study aimed to assess the association of the prooxidant
      myeloperoxidase (MPO) and the antioxidant extracellular superoxide dismutase
      (SOD3) with cardiometabolic risk factors and with prevalence and incidence of
      DSPN. METHODS: Cross-sectional analyses comprised 1069 participants (40.3% with
      prediabetes and 20.5% with type 2 diabetes) of the population-based Cooperative
      Health Research in the Region of Augsburg (KORA) F4 study (2006-2008), 181 of
      whom had DSPN at baseline. Prospective analyses included 524 individuals without
      DSPN at baseline who also participated in the KORA FF4 study (2013-2014), 132 of
      whom developed DSPN during the 6.5-year follow-up. Serum MPO and SOD3 were
      measured by ELISA, and their association with cardiometabolic risk factors and
      DSPN were estimated by using linear and logistic regression analyses. RESULTS:
      Higher MPO and SOD levels showed multiple positive associations with
      cardiometabolic risk factors including age, indices of obesity, insulin
      resistance, serum lipids, renal dysfunction, and biomarkers of inflammation.
      Higher MPO levels were associated with prevalent DSPN (fully adjusted OR 1.38
      [95% CI 1.10; 1.72] per doubling of MPO). Higher baseline SOD3 levels were
      related to incident DSPN (age and sex-adjusted OR 2.14 [1.02; 4.48] per doubling
      of SOD3), which was partially explained by cardiometabolic risk factors.
      CONCLUSIONS: Systemic levels of both pro- and antioxidant enzymes appear involved
      in cardiometabolic risk and development of DSPN.

PMID- 29577558
TI  - A systematic review and meta-analysis comparing adverse events and functional
      outcomes of different pouch designs after restorative proctocolectomy.
AB  - AIM: There is no consensus as to which ileoanal pouch design provides better
      outcomes after restorative proctocolectomy. This study compares different pouch
      designs. METHOD: A systematic review of the literature was performed. A random
      effects meta-analytical model was used to compare adverse events and functional
      outcome. RESULTS: Thirty comparative studies comparing J, W, S and K pouch
      designs were included. No significant differences were identified between the
      different pouch designs with regard to anastomotic dehiscence, anastomotic
      stricture, pelvic sepsis, wound infection, pouch fistula, pouch ischaemia,
      perioperative haemorrhage, small bowel obstruction, pouchitis and sexual
      dysfunction. The W and K designs resulted in fewer cases of pouch failure
      compared with the J and S designs. J pouch construction resulted in a smaller
      maximum pouch volume compared with W and K pouches. Stool frequency per 24 h and
      during daytime was higher following a J pouch than W, S or K constructions. The J
      design resulted in increased faecal urgency and seepage during daytime compared
      with the K design. The use of protective pads during daytime and night-time was
      greater with a J pouch compared to S or K. The use of antidiarrhoeal medication
      was greater after a J reservoir than a W reservoir. Difficulty in pouch
      evacuation requiring intubation was higher with an S pouch than with W or J
      pouches. CONCLUSION: Despite its ease of construction and comparable complication
      rates, the J pouch is associated with higher pouch failure rates and worse
      function. Patient characteristics, technical factors and surgical expertise
      should be considered when choosing pouch design.

PMID- 29577559
TI  - Tracing the fate of steroids through a hypersaline microbial mat (Kiritimati,
      Kiribati/Central Pacific).
AB  - Eukaryotic steranes are typically absent or occur in very low concentrations in
      Precambrian sedimentary rocks. However, it is as yet unclear whether this may
      reflect low source inputs or a preservational bias. For instance, it has been
      proposed that eukaryotic lipids were profoundly degraded in benthic microbial
      mats that were ubiquitous prior to the advent of vertical bioturbation in the
      Cambrian ("mat-seal effect"). It is therefore important to test the microbial
      turnover and degradation of eukaryotic steroids in real-world microbial mats.
      Here we assessed steroid inventories in different layers of a microbial mat from
      a hypersaline lake on Kiritimati (Central Pacific). Various eukaryote-derived C27
      -C30 steroids were detected in all mat layers. These compounds most likely
      entered the mat system as unsaturated sterols from the water column or the
      topmost mat, and were progressively altered during burial in the deeper, anoxic
      mat layers over c. 103  years. This is reflected by increasing proportions of
      saturated sterols and sterenes, as well as the presence of thiosteranes in
      certain horizons. Sterol alteration can partly be assigned to microbial
      transformation but is also due to chemical reactions promoted by the reducing
      environment in the deeper mat layers. Notably, however, compounds with a sterane
      skeleton were similarly abundant in all mat layers and their absolute
      concentrations did not show any systematic decrease. The observed decrease of
      steroid/hopanoid ratios with depth may thus rather indicate a progressive
      "dilution" by lipids derived from heterotrophic bacteria. Further, pyrolysis
      revealed that steroids, in contrast to hopanoids, were not sequestered into non
      extractable organic matter. This may lead to a preservational bias against
      steroids during later stages of burial. Taken together, steroid preservation in
      the microbial mat is not only controlled by heterotrophic degradation, but rather
      reflects a complex interplay of taphonomic processes.

PMID- 29577560
TI  - Prevalence and severity of nonalcoholic fatty liver disease by transient
      elastography: Genetic and metabolic risk factors in a general population.
AB  - BACKGROUND & AIMS: The worldwide spread of obesity is leading to a dramatic
      increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) and its
      complications. We aimed to evaluate both prevalence and factors associated with
      NAFLD in a general population in a Mediterranean area. METHODS: We considered 890
      consecutive individuals included in the community-based ABCD (Alimentazione,
      Benessere Cardiovascolare e Diabete) study (ISRCTN15840340). Controlled
      attenuation parameter (CAP) and liver stiffness measurement (LSM) were measured
      with FibroScan. Participants were genotyped for PNPLA3 rs738409 and TM6SF2
      rs58542926 variants. RESULTS: The prevalence of NAFLD in the cohort was 48%.
      NAFLD participants exhibited elevated LSM values, suggesting advanced fibrosis
      (6.5% of cases). Both NAFLD and advanced fibrosis were independently associated
      with traditional risk factors (NAFLD: age >50 years, obesity, hypertension,
      elevated ALT and low HDL-cholesterol serum concentrations. Advanced fibrosis:
      IFG/diabetes, elevated ALT serum concentrations). A high prevalence (>60%) of
      NAFLD was found in obese people, while it varied widely in non-obese people
      according to the presence of metabolic risk factors. PNPLA3 G variant (OR = 1.33,
      95% C.I. = 1.01-1.8; P < .05) was independently associated with NAFLD. Prevalence
      of advanced fibrosis (high LSM values) ranged from 3.4% (no risk factors) to 60%
      (presence of all risk factors). TM6SF2 T variant (OR = 3.06, 95% C.I. = 1.08
      8.65, P < .05) was independently associated with advanced fibrosis (high LSM
      values). CONCLUSIONS: In a cohort of a general population, the prevalence of
      NAFLD was very high, and among NAFLD patients a significant proportion had
      advanced fibrosis (high LSM values). Apart from traditional risk factors, genetic
      factors may have a significant role that needs to be further investigated.

PMID- 29577561
TI  - Public online reporting from a nationwide population-based clinical prostate
      cancer register.

PMID- 29577562
TI  - Dermatological manifestations in hemodialysis patients in Iran: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Dermatologic complications are common in patients with end-stage
      renal disease and also have a high diversity. OBJECTIVES: This meta-analysis
      reviews prevalence of dermatological manifestations among hemodialysis patients
      in Iran. MATERIALS AND METHODS: Using PubMed and NLM Gateway (for MEDLINE),
      Institute of Scientific Information (ISI), and SCOPUS as the main international
      electronic data sources, and Iran-Medex, Irandoc, and Scientific Information
      Database, as the main domestic databases with systematic search capability, we
      systematically searched surveys, papers, and reports on the prevalence of
      dermatological manifestations (until February 2016). Heterogeneity of reported
      prevalence's between studies was assessed using the Q test; overall prevalence of
      dermatological manifestations was estimated using random-effect meta-analysis
      model. RESULTS: We found 1229 records; from them, a total of eight studies
      comprising 917 hemodialysis patients were included. In all of studies, skin
      discoloration, pruritus and xerosis have the highest prevalence. According to
      random-effect meta-analysis model, the pooled prevalence of skin discoloration,
      pruritus, ecchymosis, xerosis, and half-and-half nail in hemodialysis patients
      were 48.03% (95% CI: 45.09-51.01), 52.85% (95%CI: 49.23-56.47), 19.88 (95% CI:
      17.57-22.19), 51.14% (95% CI: 48.25-54.02), and 18.50% (95% CI: 16.0-21.0),
      respectively. CONCLUSIONS: his study shows that the prevalence of dermatological
      manifestations seems high among the hemodialysis patients in Iran, and skin
      discoloration, pruritus, and xerosis are more common.

PMID- 29577564
TI  - Prescription drug diversion is becoming a lucrative business in regional and
      rural Australian communities and is escalating due to methamphetamine withdrawal.

PMID- 29577563
TI  - Cohort study with 4-year follow-up of myopia and refractive parameters in primary
      schoolchildren in Baoshan District, Shanghai.
AB  - IMPORTANCE: Cohort studies could not only reveal associations between change of
      refractive components and onset/progression of myopia, but also risk factors,
      which is important for understanding mechanism and providing strategies.
      BACKGROUND: Prevalence of myopia is high in Shanghai, being reported to be 52.2%
      in children aged 10 years old. DESIGN: Cohort study. PARTICIPANTS: A total of
      1856 students from six randomly selected primary schools in Baoshan District,
      Shanghai. METHODS: Children underwent comprehensive ocular measurement, including
      axial length (AL), corneal curvature radius and cycloplegic auto-refraction.
      Questionnaires about eye usage time were collected. Grade 1 students were
      followed for 4 years, and grade 2 and 3 students for 2 years. MAIN OUTCOME
      MEASURES: (i) Change of spherical equivalent (SE) and AL and (ii) risk factors
      for progression and incidence of myopia. RESULTS: The average 2-year progress of
      SE was 0.91D, 0.91D and 1.11D for grade 1, 2 and 3, respectively, and the average
      elongation of AL was 0.70 mm, 0.64 mm and 0.71 mm, respectively. Only parental
      myopia, but not near work time, near work diopter time, outdoor activity time or
      attending tutoring classes, was associated with myopia incidence and progression
      in the present population. Using baseline SE could be a simple and effective
      indicator for myopia prediction. CONCLUSIONS AND RELEVANCE: Incidence and
      progression of myopia is relatively high in schoolchildren in Shanghai compared
      with children of Western countries, East Asia and other parts of China. Effective
      strategies to control myopia prevalence are in urgent need.

PMID- 29577565
TI  - Response to the letter entitled: Developing an adherence in hypertension
      questionnaire short version, MUAH-16: Statistical and methodological issues.

PMID- 29577568
TI  - High impact exercise may cause pelvic floor dysfunction: FOR: Scale, strengthen,
      protect!

PMID- 29577569
TI  - High impact exercise may cause pelvic floor dysfunction: AGAINST: Is high-impact
      exercise really bad for your pelvic floor?

PMID- 29577566
TI  - OsPK2 encodes a plastidic pyruvate kinase involved in rice endosperm starch
      synthesis, compound granule formation and grain filling.
AB  - Starch is the main form of energy storage in higher plants. Although several
      enzymes and regulators of starch biosynthesis have been defined, the complete
      molecular machinery remains largely unknown. Screening for irregularities in
      endosperm formation in rice represents valuable prospect for studying starch
      synthesis pathway. Here, we identified a novel rice white-core endosperm and
      defective grain filling mutant, ospk2, which displays significantly lower grain
      weight, decreased starch content and alteration of starch physicochemical
      properties when compared to wild-type grains. The normal starch compound granules
      were drastically reduced and more single granules filled the endosperm cells of
      ospk2. Meanwhile, the germination rate of ospk2 seeds after 1-year storage was
      observably reduced compared with wild-type. Map-based cloning of OsPK2 indicated
      that it encodes a pyruvate kinase (PK, ATP: pyruvate 2-O-phosphotransferase, EC
      2.7.1.40), which catalyses an irreversible step of glycolysis. OsPK2 has a
      constitutive expression in rice and its protein localizes in chloroplasts. Enzyme
      assay showed that the protein product from expressed OsPK2 and the crude protein
      extracted from tissues of wild-type exhibits strong PK activity; however, the
      mutant presented reduced protein activity. OsPK2 (PKpalpha1) and three other
      putative rice plastidic isozymes, PKpalpha2, PKpbeta1 and PKpbeta2, can interact
      to form heteromer. Moreover, the mutation leads to multiple metabolic disorders.
      Altogether, these results denote new insights into the role of OsPK2 in plant
      seed development, especially in starch synthesis, compound granules formation and
      grain filling, which would be useful for genetic improvement of high yield and
      rice grain quality.

PMID- 29577570
TI  - Corrigenda.

PMID- 29577572
TI  - Should clinical guidelines dictate clinical care?

PMID- 29577571
TI  - The evolution of myomectomy: from laparotomy to minimally invasive surgery.

PMID- 29577573
TI  - Author's reply re re: Vaginal seeding or vaginal microbial transfer from the
      mother to the caesarean-born neonate: a commentary regarding clinical management.

PMID- 29577574
TI  - The effect of a practice-based multicomponent intervention that includes health
      coaching on medication adherence and blood pressure control in rural primary
      care.
AB  - Low adherence to anti-hypertensive medications contributes to worse outcomes. The
      authors conducted a secondary data analysis to examine the effects of a health
      coaching intervention on medication adherence and blood pressure (BP), and to
      explore whether changes in medication adherence over time were associated with
      changes in BP longitudinally in 477 patients with hypertension. Data regarding
      medication adherence and BP were collected at baseline, 6, 12, 18, and 24 months.
      The intervention resulted in increases in medication adherence (5.75->5.94, P =
      .04) and decreases in diastolic BP (81.6->76.1 mm Hg, P < .001) over time. The
      changes in medication adherence were associated with reductions in diastolic BP
      longitudinally (P = .047). Patients with low medication adherence at baseline had
      significantly greater improvement in medication adherence and BP over time than
      those with high medication adherence. The intervention demonstrated improvements
      in medication adherence and diastolic BP and offers promise as a clinically
      applicable intervention in rural primary care.

PMID- 29577575
TI  - One-year clinical outcomes of locking taper Equator attachments retaining
      mandibular overdentures to narrow diameter implants.
AB  - BACKGROUND: Narrow diameter implants (NDI) are recommended to retain mandibular
      overdentures (MOs) in cases of limited bone thickness. It is necessary to
      evaluate the clinical behavior of NDI as MO retainers connected to a new
      screwless locking taper abutments, their predictability and maintenance problems.
      OBJECTIVES: To evaluate the peri-implant tissue behavior around NDI and the
      performance of locking taper stud abutments as MO retainers. METHODOLOGY: Thirty
      patients (average age of 67.5 years) received 2 NDI implants (2.9 * 10 mm) loaded
      after 12 weeks using Equator stud attachments. The plaque index (PI), calculus
      index (CI), gingival index (GI), probing depth (PD), bleeding on probing (BOP),
      and implant stability quotient (ISQ) were monitored during osseointegration at 0,
      4, 8, and 12 weeks and postloading at 24, 48, and 60 weeks. The marginal bone
      level (MBL) and bone level changes (BLC) were determined at baseline and 60
      weeks. RESULTS: The cumulative success rate was 83.3%. The PI oscillated in the
      first 24 weeks and decreased from 48 weeks onward, while the CI score showed
      significantly higher values at week 8 (22%). The GI also peaked at week 8 (18.6%)
      and decreased from week 12 onward. The PD decreased gradually over time, but no
      significant differences were found between weeks 8 and 12. The ISQ decreased
      significantly between 0 and 12 weeks. After MO loading, the ISQ values increased
      linearly and significantly between 12 and 24, 24 and 48, and 48 and 60 weeks and
      reached values similar to the primary stability after 60 weeks [56.1(42.0-65.3)].
      No significant MBL was observed at 60 weeks, with an average BLC of -0.06 +/-
      0.64 mm. CONCLUSION: NDI connected to locking taper Equator attachments showed a
      stable clinical behavior as an MO retainer for edentulous patients with clinical
      mandibular atrophy.

PMID- 29577576
TI  - Self-assembled, ellipsoidal polymeric nanoparticles for intracellular delivery of
      therapeutics.
AB  - Nanoparticle shape has emerged as a key regulator of nanoparticle transport
      across physiological barriers, intracellular uptake, and biodistribution. We
      report a facile approach to synthesize ellipsoidal nanoparticles through self
      assembly of poly(glycerol sebacate)-co-poly(ethylene glycol) (PGS-co-PEG). The
      PGS-PEG nanoparticle system is highly tunable, and the semiaxis length of the
      nanoparticles can be modulated by changing PGS-PEG molar ratio and incorporating
      therapeutics. As both PGS and PEG are highly biocompatible, the PGS-co-PEG
      nanoparticles show high hemo-, immuno-, and cytocompatibility. Our data suggest
      that PGS-co-PEG nanoparticles have the potential for use in a wide range of
      biomedical applications including regenerative medicine, stem cell engineering,
      immune modulation, and cancer therapeutics. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 2048-2058, 2018.

PMID- 29577577
TI  - Pigment carbon and nitrogen isotopic signatures in euxinic basins.
AB  - The carbon and nitrogen isotopic signatures of chloropigments and porphyrins from
      the sediments of redox-stratified lakes and marine basins reveal details of past
      biogeochemical nutrient cycling. Such interpretations are strengthened by modern
      calibration studies, and here, we report on the C and N isotopic composition of
      pigments and nutrients in the water column and surface sediment of redox
      stratified Fayetteville Green Lake (FGL; New York). We also report delta13 C and
      delta15 N values for pyropheophytin a (Pphe a) and bacteriochlorophyll e (Bchl e)
      deposited in the Black Sea during its transition to a redox-stratified basin ca.
      7.8 ka. We propose a model for evolving nutrient cycling in the Black Sea from
      7.8 to 6.4 ka, informed by the new pigment data from FGL. The seasonal study of
      water column nutrients and pigments at FGL revealed population dynamics in
      surface and deep waters that were also captured in the sediments. Biomass was
      greatest near the chemocline, where cyanobacteria, purple sulfur bacteria (PSB),
      and green sulfur bacteria (GSB) had seasonally variable populations. Bulk organic
      matter in the surface sediment, however, was derived mainly from the oxygenated
      surface waters. Surface sediment pigment delta13 C and delta15 N values indicate
      intact chlorophyll a (Chl a) was derived from near the chemocline, but its
      degradation product pheophytin a (Phe a) was derived primarily from surface
      waters. Bacteriopheophytin a (Bphe a) and Bchl e in the sediments came from
      chemocline populations of PSB and GSB, respectively. The distinctive delta13 C
      and delta15 N values for Chl a, Phe a, and Bphe a in the surface sediment are
      inputs to an isotopic mixing model that shows their decomposition to a common
      porphyrin derivative can produce non-specific sedimentary isotope signatures.
      This model serves as a caveat for paleobiogeochemical interpretations in basins
      that had diverse populations near a shallow chemocline.

PMID- 29577578
TI  - Quantification of beam steering with an ionization chamber array.
AB  - Routine quality assurance for linear accelerators (linacs) usually involves
      verification of beam steering with a water scanning system. We established a beam
      steering procedure that uses a 2D ionization chamber array (ICA) and verified the
      equivalence of beam symmetry between the ICA and a water scanning system. The ICA
      calibration accuracy, reproducibility and stability were evaluated and the
      uncertainty in the measurement of beam symmetry due to the array calibration was
      examined. Forty-five photon beams and 80 electron beams across 7 Varian C-series
      and 4 TrueBeam linacs were steered in the radial and transverse directions using
      an ICA. After beam steering, profiles were re-measured using the ICA and in-water
      using a 3D Scanner (3DS). Beam symmetries measured with the ICA and 3DS were
      compared by (a) calculating the difference in point-by-point symmetry, (b)
      plotting the histogram distribution of the symmetry differences, and (c)
      comparing ICA and 3DS differences with their respective Varian symmetry protocol
      analysis. Array calibrations from five different occurrences (2012 to 2016) over
      six different beams reproduced within 0.5%. The uncertainty in beam symmetry was
      less than 0.5% due to the uncertainties in the array calibration. After all beams
      were steered using the ICA, the point-by-point symmetry differences between ICA
      and 3DS at the off-axis positions of 20% and 80% of field size for all beam
      profiles indicated that 95% of point-by-point symmetry comparisons agreed within
      0.7%, and 100% agreed within 1.0%; after steering with the ICA 97.8% of photon
      beam profiles (88 of 90) and 97.5% of electron beam profiles (156 of 160) had
      symmetry within 1% when measured with the 3DS. All photon and electron beam
      profiles had symmetry within 1.1% and 1.2%, respectively, for profiles measured
      with the 3DS. Our data demonstrate that a calibrated ICA can be used to steer
      photon and electron beams achieving beam symmetry within 1% when re-measured with
      a 3D water scanning system.

PMID- 29577579
TI  - Hepatic and cardiac beneficial effects of a long-acting Fc-apelin fusion protein
      in diet-induced obese mice.
AB  - BACKGROUND: Apelin is a peptide ligand of the G-protein-coupled receptor APJ and
      exhibits anti-diabetes and anti-heart failure activities. However, short serum
      half-life of the apelin peptide limits its potential clinical applications. This
      study aimed to develop a long-acting apelin analog. METHODS: To extend apelin's
      in vivo half-life, we made a recombinant protein by fusing the IgG Fc fragment to
      apelin-13 (Fc-apelin-13), conducted pharmacokinetics studies in mice, and
      determined in vitro biological activities in suppressing cyclic adenosine
      monophosphate and activating extracellular signal-regulated kinase signalling by
      reporter assays. We investigated the effects of Fc-apelin-13 on food intake, body
      weight, fasting blood glucose and insulin levels, glucose tolerance test, hepatic
      steatosis, and cardiac function and fibrosis by subcutaneous administration of Fc
      apelin-13 in diet-induced obese mice for 4 weeks. RESULTS: The estimated half
      life of Fc-apelin-13 in blood was approximately 33 hours. Reporter assays showed
      that Fc-apelin-13 was active in suppressing cyclic adenosine monophosphate
      response element and activating serum response element activities. Four weeks of
      Fc-apelin-13 treatment in obese mice did not affect food intake and body weight,
      but resulted in a significant improvement of glucose tolerance, and a decrease in
      hepatic steatosis and fibrosis, as well as in serum alanine transaminase levels.
      Moreover, cardiac stroke volume and output were increased and cardiac fibrosis
      was decreased in the treated mice. CONCLUSIONS: Fc-apelin-13 fusion protein has
      an extended in vivo half-life and exerts multiple benefits on obese mice with
      respect to the improvement of glucose disposal, amelioration of liver steatosis
      and heart fibrosis, and increase of cardiac output. Hence, Fc-apelin-13 is
      potentially a therapeutic for obesity-associated disease conditions.

PMID- 29577580
TI  - Development of a new 3-DOF parallel manipulator for minimally invasive surgery.
AB  - This article proposes a novel dexterous endoscopic parallel manipulator for
      minimally invasive surgery. The proposed manipulator has 3 degrees of freedom (3
      DOF), which consist of two rotational DOFs and one translational DOF (2R1T DOFs).
      The manipulator consists of 3 limbs exhibiting identical kinematic structure.
      Each limb contains an active prismatic joint followed by 2 consecutive passive
      universal joints. The proposed manipulator has a unique arrangement of its
      joints' axes. This unique arrangement permits large bending angles, +/-90 degrees
      in any direction, and a workspace almost free from interior singularities. These
      advantages allow the proposed manipulator to outperforms existing surgical
      manipulators. However, this unique arrangement makes the analysis of the robot
      extremely difficult. Therefore, a geometrical/analytical approach is used to
      facilitate its singularity analysis. Construction of the virtual prototype is
      accomplished using ADAMS software to validate the proposed manipulator and its
      bending capability. A closed-form solution for inverse kinematics is obtained
      analytically. Also, the forward kinematics solution is obtained numerically.
      Moreover, evaluation of the workspace is achieved using motion/force
      transmissibility indices. A practical experiment has been performed using a
      scaling technique and PID controller. The experimental results show the
      feasibility of the teleoperated surgical system using the proposed parallel
      manipulator as the slave.

PMID- 29577581
TI  - Hepatitis C Virus Eradication with New Interferon-Free Treatment Improves
      Metabolic Profile in Hepatitis C Virus-Related Liver Transplant Recipients.
AB  - Interferon (IFN)-free, direct-acting antiviral (DAA) therapy agents provide a
      safe and efficacious treatment for liver transplant recipients with recurrent
      hepatitis C virus (HCV) infection. The aim of this study is to evaluate the
      impact of HCV eradication on the metabolic factors in liver transplant
      recipients. We completed a retrospective single-center study on HCV-related liver
      transplant recipients treated with IFN-free DAAs including both treatment-naive
      and treatment-experienced patients. IFN-free DAAs impact on the metabolic profile
      were assessed at baseline and sustained virological response (SVR) between 24 and
      48 weeks. In total, 91 liver transplant recipients with recurrent HCV infection
      received IFN-free DAA treatment, 62 patients had IFN-based treatment failure, and
      29 were treatment-naive, of whom 87 (96%) achieved SVR. Eradication of recurrent
      HCV infection was associated with reduction in the treatment of diabetes and
      hypertension by 38% and 22% from the baseline respectively. Hemoglobin A1c
      (HbA1c) levels declined from mean 35.5 +/- 4.3 mmol/mol to 33.3 +/-3.6 mmol/mol
      at 44 weeks posttreatment (P = 0.03). Total cholesterol levels increased from 3.8
      +/- 0.9 mmol/L to 4.9 +/- 0.9 mmol/L at 41 weeks posttreatment (P < 0.0001),
      reflecting a significant increase in serum low-density lipoprotein (LDL) levels
      (2.0 +/- 0.8 to 2.9 +/- 0.8; P < 0.0001). Estimated glomerular filtration rate
      (eGFR) levels increased from 64.9 +/- 20 mL/minute to 69.6 +/- 20 mL/minute at 24
      weeks posttreatment (P = 0.0004). Glucose, lipid profile, and eGFR changes were
      independent of weight changes and immunosuppression dosage and trough levels. In
      conclusion, eradication of recurrent HCV infection by DAA therapy has beneficial
      impacts on glucose metabolism and renal profile and reverses the hypolipidemic
      effect of HCV in liver transplant recipients. These extrahepatic effects of DAA
      therapy need to be validated by larger prospective studies.

PMID- 29577583
TI  - Conscientious objection in reproductive health - ancient prerogative or harmful
      practice.

PMID- 29577582
TI  - The genetic component of human longevity: New insights from the analysis of
      pathway-based SNP-SNP interactions.
AB  - In human longevity studies, single nucleotide polymorphism (SNP) analysis
      identified a large number of genetic variants with small effects, yet not easily
      replicable in different populations. New insights may come from the combined
      analysis of different SNPs, especially when grouped by metabolic pathway. We
      applied this approach to study the joint effect on longevity of SNPs belonging to
      three candidate pathways, the insulin/insulin-like growth factor signalling
      (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs
      in 140 genes, collected in 1825 subjects (1,089 unrelated nonagenarians from the
      Danish 1905 Birth Cohort Study and 736 Danish controls aged 46-55 years) for
      evaluating synergic interactions by SNPsyn. Synergies were further tested by the
      multidimensional reduction (MDR) approach, both intra- and interpathways. The
      best combinations (FDR<0.0001) resulted those encompassing IGF1R-rs12437963 and
      PTPN1-rs6067484, TP53-rs2078486 and ERCC2-rs50871, TXNRD1-rs17202060 and TP53
      rs2078486, the latter two supporting a central role of TP53 in mediating the
      concerted activation of the DNA repair and pro-antioxidant pathways in human
      longevity. Results were consistently replicated with both approaches, as well as
      a significant effect on longevity was found for the GHSR gene, which also
      interacts with partners belonging to both IIS and DNA repair pathways (PAPPA,
      PTPN1, PARK7, MRE11A). The combination GHSR-MREA11, positively associated with
      longevity by MDR, was further found influencing longitudinal survival in
      nonagenarian females (p = .026). Results here presented highlight the validity of
      SNP-SNP interactions analyses for investigating the genetics of human longevity,
      confirming previously identified markers but also pointing to novel genes as
      central nodes of additional networks involved in human longevity.

PMID- 29577584
TI  - Fabrication and evaluation of interconnected porous carbonate apatite from alpha
      tricalcium phosphate spheres.
AB  - Carbonate apatite (CO3 Ap) blocks have attracted considerable attention as an
      artificial bone substitute material because CO3 Ap is a component of and shares
      properties with bone, including high osteoconductivity and replacement by bone
      similar to autografts. In this study, we fabricated an interconnected porous CO3
      Ap block using alpha-tricalcium phosphate (TCP) spheres and evaluated the tissue
      response to this material in a rabbit tibial bone defect model. Interconnected
      porous alpha-TCP, the precursor of interconnected porous CO3 Ap, could not be
      fabricated directly by sintering alpha-TCP spheres. It was therefore made via a
      setting reaction with alpha-TCP spheres, yielding interconnected porous calcium
      deficient hydroxyapatite that was subjected to heat treatment. Immersing the
      interconnected porous alpha-TCP in Na-CO3 -PO4 solution produced CO3 Ap, which
      retained the interconnected porous structure after the dissolution-precipitation
      reaction. The diametral tensile strength and porosity of the porous CO3 Ap were
      1.8 +/- 0.4 MPa and 55% +/- 3.2%, respectively. Both porous and dense (control)
      CO3 Ap showed excellent tissue response and good osteoconductivity. At 4 weeks
      after surgery, approximately 15% +/- 4.9% of the tibial bone defect was filled
      with new bone when reconstruction was performed using porous CO3 Ap; this amount
      was five times greater than that obtained with dense CO3 Ap. At 12 weeks after
      surgery, for porous CO3 Ap, approximately 47% of the defect was filled with new
      bone as compared to 16% for dense CO3 Ap. Thus, the interconnected porous CO3 Ap
      block is a promising artificial bone substitute material for the treatment of
      bone defects caused by large fractures or bone tumor resection. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29577585
TI  - nNOS-CAPON interaction mediates amyloid-beta-induced neurotoxicity, especially in
      the early stages.
AB  - In neurons, increased protein-protein interactions between neuronal nitric oxide
      synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) contribute to
      excitotoxicity and abnormal dendritic spine development, both of which are
      involved in the development of Alzheimer's disease. In models of Alzheimer's
      disease, increased nNOS-CAPON interaction was detected after treatment with
      amyloid-beta in vitro, and a similar change was found in the hippocampus of
      APP/PS1 mice (a transgenic mouse model of Alzheimer's disease), compared with age
      matched background mice in vivo. After blocking the nNOS-CAPON interaction,
      memory was rescued in 4-month-old APP/PS1 mice, and dendritic impairments were
      ameliorated both in vivo and in vitro. Furthermore, we demonstrated that S
      nitrosylation of Dexras1 and inhibition of the ERK-CREB-BDNF pathway might be
      downstream of the nNOS-CAPON interaction.

PMID- 29577586
TI  - In vivo efficacy and properties of semisolid formulations containing panthenol.
AB  - BACKGROUND: Panthenol is an active substance used in dermatology to protect the
      health of the skin, to treat defects in the morphology of the stratum corneum. In
      cosmetology, hydrating, softening, and barrier function of panthenol are
      utilized. Detailed studies evaluating the efficacy of panthenol in cosmetic and
      pharmaceutical semisolid formulations and establishing its optimum concentration
      are needed. OBJECTIVES: To investigate whether an addition of 5-13 wt% panthenol
      in o/w and w/o emulsions increases hydration and supports the barrier properties
      of the skin. Rheological properties and sensory analysis of prepared formulations
      are supplemented. METHODS: Noninvasive instrumental methods in vivo were used.
      The hydration and barrier effect of semisolid formulations on the skin were
      observed for 48 hour; testing was conducted on 40 women. The effect was compared
      with formulations without any content of panthenol. The rheological and
      organoleptic properties of the formulations were evaluated. RESULTS: After
      applying either form of the formulations containing 7-11 wt% of panthenol
      hydration of the skin increased, transepidermal water loss decreased. pH of the
      skin shifted toward neutral after application of tested formulations. The
      rheological properties of the formulations were influenced by the type of
      vehicle, the amount of panthenol, and temperature. Sensory evaluation of both
      semisolid forms revealed statistically significant differences in o/w
      formulations with regard to spreadability. CONCLUSIONS: The presence of panthenol
      in an o/w and w/o semisolid formulations significantly enhances skin barrier
      repair and hydration of the stratum corneum. Better vehicle for the active
      substance as regards hydration proved o/w formulations.

PMID- 29577587
TI  - Influence of CuO/MgO ratio on the gene expression, cytocompatibilty, and
      antibacterial/anticancerous/analgesic drug loading kinetics for (15-x) CuO-xMgO
      10P2 O5 -60SiO2 -10CaO-5ZnO (2.5 <= x <= 12.5) mesoporous bioactive glasses.
AB  - In the present study, novel mesoporous bioactive glasses (MBGs) (15-x)CuO-xMgO
      10P2 O5 -60SiO2 -10CaO-5ZnO (2.5 <= x <= 12.5, varying in steps of 2) are
      synthesized using the sol-gel technique. The structural phases of the
      glasses/glass ceramics were studied by XRD. The pH variation and simulated body
      fluids (SBF) studies demonstrated the in-vitro bioactivity of all the MBGs. MBGs
      possess surface area variation between 98.22 and 442.41 cm2 /g. The pore size of
      MBGs lies in the range of 5.8-8.8 nm. The cytotoxicity assays were conducted for
      MG63 human osteosarcoma cell line depicting non-toxic behavior of all MBGs at
      7.8125 MUg/ml. In addition to this, the effect of the magnesium on the gene
      expression was also investigated using reverse transcription-polymerase chain
      reaction (RT-qPCR). The MBGs were loaded with the antibacterial
      (vancomycin/amoxicillin), anticancerous (doxorubicin), and analgesic (Iburofen)
      drugs. Ibuprofen and amoxicillin drugs were almost fully loaded in all the MBGs,
      whereas doxorubicin and vancomycin drugs illustrated variation in loading with
      decreasing copper content. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 2116-2130, 2018.

PMID- 29577589
TI  - Correlation of infarct size with invasive hemodynamics in patients with ST
      elevation myocardial infarction.
AB  - OBJECTIVES: To identify invasive hemodynamic parameters that correlate with
      infarction size in patients with ST-elevation myocardial infarction (STEMI).
      BACKGROUND: Invasive hemodynamics obtained during primary percutaneous coronary
      intervention (PPCI) are predictive of mortality in STEMI, but which parameters
      correlate best with the size of the infarction are unknown. METHODS: This is a
      single-center study of 405 adult patients with STEMI who had left ventricular end
      diastolic pressure (LVEDP) measured during PPCI. Size of infarction was estimated
      by peak troponin I level and ejection fraction (LVEF) determined by
      echocardiography. RESULTS: The average (+/-SD) age was 61 +/- 14 years, TIMI
      STEMI risk score was 3.5 +/- 2.7 and Grace score was 157 +/- 42. Hemodynamic
      parameters that correlated best with EF were LVEDP (r = -0.40), PP (r = 0.24),
      and SBP/LVEDP ratio (r = 0.22) and with peak troponin were SBP/LVEDP ratio (r = 
      0.41), LVEDP (r = 0.31), and PP (r = -0.29). SBP/LVEDP (AUC = 0.76) and SBP (AUC
      = 0.77) had a stronger association with in-hospital mortality than did LVEDP (AUC
      = 0.66) or PP (AUC = 0.64). Door-to-balloon time did not affect the correlations
      between hemodynamic parameters and infarct size. CONCLUSIONS: In this sample of
      405 patients undergoing PPCI, SBP/LVEDP ratio had the strongest correlation with
      peak troponin levels and LVEDP with EF, whereas SBP/LVEDP and SBP had a strong
      association with in-hospital mortality. These results suggest that measurement of
      LVEDP as well as SBP may help risk stratify patients during PPCI.

PMID- 29577590
TI  - Confined Assembly of Hollow Carbon Spheres in Carbonaceous Nanotube: A Spheres-in
      Tube Carbon Nanostructure with Hierarchical Porosity for High-Performance
      Supercapacitor.
AB  - Carbonaceous nanotubes (CTs) represent one of the most popular and effective
      carbon electrode materials for supercapacitors, but the electrochemistry
      performance of CTs is largely limited by their relatively low specific surface
      area, insufficient usage of intratube cavity, low content of heteroatom, and poor
      porosity. An emerging strategy for circumventing these issues is to design novel
      porous CT-based nanostructures. Herein, a spheres-in-tube nanostructure with
      hierarchical porosity is successfully engineered, by encapsulating heteroatom
      doping hollow carbon spheres into one carbonaceous nanotube (HCSs@CT). This
      intriguing nanoarchitecture integrates the merits of large specific surface area,
      good porosity, and high content of heteroatoms, which synergistically facilitates
      the transportation and exchange of ions and electrons. Accordingly, the as
      prepared HCSs@CTs possess outstanding performances as electrode materials of
      supercapacitors, including superior capacitance to that of CTs, HCSs, and their
      mixtures, coupled with excellent cycling life, demonstrating great potential for
      applications in energy storage.

PMID- 29577591
TI  - Effects of antigen removal on a porcine osteochondral xenograft for articular
      cartilage repair.
AB  - Given the limited availability of fresh osteochondral allografts and uncertainty
      regarding performance of decellularized allografts, this study was undertaken as
      part of an effort to develop an osteochondral xenograft for articular cartilage
      repair. The purpose was to evaluate a simple antigen removal procedure based
      mainly on treatment with SDS and nucleases. Histology demonstrated a preservation
      of collagenous structure and removal of most nuclei. Immunohistochemistry
      revealed the apparent retention of alpha-Gal within osteocyte lacunae unless the
      tissue underwent an additional alpha-galactosidase processing step. Cytoplasmic
      protein was completely removed as shown by Western blot. Quantitatively, the
      antigen removal protocol was found to extract approximately 90% of DNA from
      cartilage and bone, and it extracted over 80% of glycosaminoglycan from
      cartilage. Collagen content was not affected. Mechanical testing of cartilage and
      bone were performed separately, in addition to testing the cartilage-bone
      interface, and the main effect of antigen removal was an increase in cartilage
      hydraulic permeability. In vivo immunogenicity was assessed by subcutaneous
      implantation into DBA/1 J mice, and the response was typical of a foreign body
      rather than immune reaction. Thus, an osteochondral xenograft produced as
      described has the potential for further development into a treatment for
      osteochondral lesions in the human knee. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 2251-2260, 2018.

PMID- 29577592
TI  - Monitoring frequency of intra-fraction patient motion using the ExacTrac system
      for LINAC-based SRS treatments.
AB  - PURPOSE: The aim of this study was to investigate the intra-fractional patient
      motion using the ExacTrac system in LINAC-based stereotactic radiosurgery (SRS).
      METHOD: A retrospective analysis of 104 SRS patients with kilovoltage image
      guided setup (Brainlab ExacTrac) data was performed. Each patient was imaged pre
      treatment, and at two time points during treatment (1st and 2nd mid-treatment),
      and bony anatomy of the skull was used to establish setup error at each time
      point. The datasets included the translational and rotational setup error, as
      well as the time period between image acquisitions. After each image acquisition,
      the patient was repositioned using the calculated shift to correct the setup
      error. Only translational errors were corrected due to the absence of a 6D
      treatment table. Setup time and directional shift values were analyzed to
      determine correlation between shift magnitudes as well as time between
      acquisitions. RESULTS: The average magnitude translation was 0.64 +/- 0.59 mm,
      0.79 +/- 0.45 mm, and 0.65 +/- 0.35 mm for the pre-treatment, 1st mid-treatment,
      and 2nd mid-treatment imaging time points. The average time from pre-treatment
      image acquisition to 1st mid-treatment image acquisition was 7.98 +/- 0.45 min,
      from 1st to 2nd mid-treatment image was 4.87 +/- 1.96 min. The greatest
      translation was 3.64 mm, occurring in the pre-treatment image. No patient had a
      1st or 2nd mid-treatment image with greater than 2 mm magnitude shifts.
      CONCLUSION: There was no correlation between patient motion over time, in
      direction or magnitude, and duration of treatment. The imaging frequency could be
      reduced to decrease imaging dose and treatment time without significant changes
      in patient position.

PMID- 29577593
TI  - Isolation and enrichment of Ginkgo biloba extract by a continuous chromatography
      system.
AB  - In this study, an effective method was developed for the isolation and enrichment
      of Ginkgo biloba extract by continuous chromatography system. The adsorption and
      desorption ratio of flavonoids as main index, the best macroporous resin was
      screened out from six resins by static adsorption and desorption tests. At the
      same time the adsorption and desorption parameters were optimized by dynamic
      adsorption and desorption tests. Under optimal parameters, five operations
      consisting of loading, washing, desorbing, regenerating, and balancing were
      integrated across the continuous chromatography system for the purpose of
      refining 66 L of crude extract solution. The results were as follows, 198.22 g of
      Ginkgo biloba extracts was produced, which contained 65.83 g of flavonoids and
      15.44 g of lactones. The content of flavonoids and lactones increased from 2.76
      and 0.72% in the crude extract to 33.21 and 7.79%, with a recovery yield of 91.26
      and 81.21%. Methodology validation showed that the proposed method had high
      stability and reproducibility. Compared with the traditional macroporous resin
      method, the proposed method had a short processing time and low solvent
      consumption. Our studies indicated that the newly developed method is an
      effective procedure for the isolation and enrichment of Ginkgo biloba extract.

PMID- 29577594
TI  - Butyrate Inhibits Indices of Colorectal Carcinogenesis via Enhancing alpha
      Ketoglutarate-Dependent DNA Demethylation of Mismatch Repair Genes.
AB  - SCOPE: Butyrate, the fermentation end product of gut microbiota in the colon, is
      known for its antitumor effects, but the mechanisms remained to be defined. alpha
      ketoglutarate (alpha-KG) mediates DNA demethylation and aberrant epigenetic
      modifications are associated with carcinogenesis. The objectives of this study
      are to evaluate the effects of butyrate on alpha-KG mediated epigenetic
      modification in colorectal adenocarcinoma HT-29 and Caco-2 cells. METHODS AND
      RESULTS: Butyrate suppressed proliferation, potentiated differentiation, and
      induced apoptosis in both HT-29 and Caco-2 cells, associated with enhanced
      expression of isocitrate dehydrogenase 1 (IDH1) and pyruvate dehydrogenase.
      Furthermore, butyrate upregulated acetyl-CoA and alpha-KG, concomitant with
      enhanced histone acetylation and DNA demethylation in the promoter of DNA
      mismatch repair (MMR) gene. Knocking down IDH1 abolished the positive effects of
      butyrate on CRC apoptosis and MMR protein expression, in conjunction with reduced
      alpha-KG content. Importantly, alpha-KG supplementation recovered the beneficial
      effects of butyrate in IDH1-deficient cells. CONCLUSION: In summary, butyrate
      inhibits indices of colorectal carcinogenesis in an alpha-KG-dependent manner.

PMID- 29577595
TI  - Comparison of different grafting materials for treatment of bone defect distal to
      the molar in canine.
AB  - BACKGROUND: The extraction of impacted mandibular 3rd molar is highly related to
      bone defect distal to the adjacent 2nd molar. PURPOSE: The aim of this study was
      to evaluate the effect of different grafting materials for the treatment of bone
      defect distal to the mandibular molar in canine model. MATERIALS AND METHODS: In
      12 beagle dogs, bilateral mandibular 2nd and 3rd molars were extracted and entire
      mesial bone of the 2nd molar extracted socket was surgically removed. Twenty-four
      bone defects (4 mm width and 8 mm depth) were randomly assigned to 4 groups, and
      grafted using 1 of the following protocols: (1) group C: no graft; (2) group Ta:
      autogenous bone (AB); (3) group Tb: deproteinized bovine bone mineral (DBBM) with
      a collagen membrane (CM); and (4) group Tab: an equal mixture of AB/DBBM + CM.
      Quantitative imageology analyses using micro-CT and fluorescence microscopy, as
      well as qualitative analyses using histological and histomorphometric
      evaluations, were characterized at postoperative 12 weeks. Significant
      differences of all variables were tested by multivariate analysis (P < .05).
      RESULTS: The defect depth was significantly lower in groups Ta, Tb, and Tab
      (1.70, 1.97, and 1.61 mm, respectively; mean) than in the group C (3.66 mm, P <
      .01, all). Compared to the sites received DBBM/CM, sites grafted with AB or
      AB/DBBM exhibited significant greater and faster new bone formation (P < .01).
      The percentage of DBBM remnants area (%) was significantly higher in group Tb
      than in group Tab (10.43% and 1.13%, P < .01; mean). CONCLUSIONS: Our data
      suggested grafting AB alone, DBBM/CM, or AB/DBBM/CM resulted in similar
      periodontal parameters in canine. Furthermore, the AB could accelerate new bone
      regeneration and mineralization, and promote the biodegradation of DBBM.

PMID- 29577596
TI  - The role of plant size in the selection of glyphosate resistance in Sorghum
      halepense.
AB  - BACKGROUND: The effect of plant size (seedlings versus young plants versus adult
      plants) on the phenotypic level of glyphosate resistance and selection intensity
      (SI) in Sorghum halepense with and without a reduced glyphosate translocation
      resistance mechanism was evaluated. RESULTS: Resistance parameters [the 50%
      lethal dose (LD50 ) and the dose required to cause a 50% reduction in plant
      growth (GR50 )] in adult plants were notably higher than in seedlings regardless
      of the resistance status. However, under similar plant size increases,
      populations comprised of glyphosate-resistant (R) individuals showed higher
      survival and growth when glyphosate treated compared with glyphosate-susceptible
      (S) plants. An increase in SI was always evident with increasing glyphosate
      doses. However, the rate of increase in SI was higher under glyphosate selection
      of young R and S plants, followed by seedlings and adult R and S plants. However,
      in conditions of R seedlings coexisting with adult S plants under glyphosate
      treatment (1000-4000 g ha-1 ), selection against glyphosate resistance was
      observed. CONCLUSION: Any increase in size from the seedling stage of R plants
      translates into an amplification of resistance. Depending on the particular size
      combinations of spatially coexisting R and S plants, selection for glyphosate
      resistance may be faster, slower or even not evident. (c) 2018 Society of
      Chemical Industry.

PMID- 29577597
TI  - Acaricidal toxicities and synergistic activities of Salvia lavandulifolia oil
      constituents against synanthropic mites.
AB  - BACKGROUND: The acaricidal activity of Salvia lavandulifolia oil and its major
      components was evaluated using contact and vapor bioassays. Synergistic
      interactions among components contained in S. lavandulifolia oil were studied.
      RESULTS: The 50% lethal dose (LD50 ) of S. lavandulifolia oil was 3.66, 3.37, and
      5.04 MUg cm-3 , respectively, in the vapor bioassay against Dermatophagoides
      farinae, Dermatophagoides pteronyssinus and Tyrophagus putrescentiae. The major
      components of S. lavandulifolia oil were (-)-camphor, camphene, 1,8-cineole, (+/
      )-limonene, and alpha-pinene (79.11% combined). Several combinations of these
      components exhibited synergistic effects against D. farinae, D. pteronyssinus,
      and T. putrescentiae, particularly (-)-camphor, camphene, and alpha-pinene. (-)
      Camphor usually had synergistic interactive effects in the mixtures. For the
      vapor action, the mixture of (-)-camphor, camphene and alpha-pinene was the most
      potent combination against D. farinae (R = 2.34), D. pteronyssinus (R = 2.75),
      and T. putrescentiae (R = 2.30) when used at their naturally occurring ratio.
      CONCLUSION: This study is the first report on the acaricidal activity of S.
      lavandulifolia oil and the synergistic interactive effects of its components
      against D. farinae, D. pteronyssinus and T. putrescentiae. The oil may be an
      alternative tool for the control of synanthropic mites. (c) 2018 Society of
      Chemical Industry.

PMID- 29577598
TI  - Pressured HIV testing "in the name of love": a mixed methods analysis of
      pressured HIV testing among men who have sex with men in China.
AB  - INTRODUCTION: HIV testing has rapidly expanded into diverse, decentralized
      settings. While increasing accessibility to HIV testing is beneficial, it may
      lead to unintended consequences such as being pressured to test. We examined the
      frequency, correlates and contexts of pressured HIV testing among Chinese men who
      have sex with men (MSM) using mixed methods. METHODS: We conducted an online
      survey of MSM (N = 1044) in May 2017. Pressured HIV testing was defined as being
      forced to test for HIV. We conducted logistic regression analysis to determine
      the associations between pressured HIV testing and socio-demographic and sexual
      behavioural factors. Follow-up interviews (n = 17) were conducted with men who
      reported pressured testing and we analysed qualitative data using a thematic
      analysis approach. RESULTS: Ninety-six men (9.2%) reported experiencing pressure
      to test for HIV. Regular male sex partners were the most common source of
      pressure (61%, 59/96), and the most common form of pressure was a threat to end a
      relationship with the one who was being pressured (39%, 37/96). We found a higher
      risk of pressured testing in men who had only used HIV self-testing compared to
      men who had never self-tested (AOR 2.39 (95%CI: 1.38 to 4.14)). However, this
      relationship was only significant among men with low education (AOR 5.88 (95% CI:
      1.92 to 17.99)) and not among men with high education (AOR 1.62 (95% CI: 0.85 to
      3.10)). After pressured testing, about half of men subsequently tested for HIV
      (55%, 53/96) without pressure - none reported being diagnosed with HIV.
      Consistent with this finding, qualitative data suggest that perceptions of
      pressure existed on a continuum and depended on the relationship status of the
      one who pressured them. Although being pressured to test was accompanied by
      negative feelings, men who were pressured into testing often changed their
      attitude towards HIV testing, testing behaviours, sexual behaviours and
      relationship with the one who pressured them to test. CONCLUSION: Pressured HIV
      testing was reported among Chinese MSM, especially from men with low education
      levels and men who received HIV self-testing. However, in some circumstances,
      pressure to test helped MSM in several ways, challenging our understanding of the
      role of agency in the setting of HIV testing.

PMID- 29577599
TI  - Proteins Identified from Saliva and Salivary Glands of the Chinese Gall Aphid
      Schlechtendalia chinensis.
AB  - Aphid saliva plays an essential role in the interaction between aphids and their
      host plants. Several aphid salivary proteins have been identified but none from
      galling aphids. Here the salivary proteins from the Chinese gall aphid are
      analyzed, Schlechtendalia chinensis, via an LC-MS/MS analysis. A total of 31
      proteins are identified directly from saliva collected via an artificial diet,
      and 141 proteins are identified from extracts derived from dissected salivary
      glands. Among these identified proteins, 17 are found in both collected saliva
      and dissected salivary glands. In comparison with salivary proteins from ten
      other free-living Hemipterans, the most striking feature of the salivary protein
      from S. chinensis is the existence of high proportion of proteins with binding
      activity, including DNA-, protein-, ATP-, and iron-binding proteins. These
      proteins maybe involved in gall formation. These results provide a framework for
      future research to elucidate the molecular basis for gall induction by galling
      aphids.

PMID- 29577600
TI  - Quantification of number of CD38 sites on bone marrow plasma cells in patients
      with light chain amyloidosis and smoldering multiple myeloma.
AB  - BACKGROUND: Recent approaches in multiple myeloma (MM) treatment have targeted
      CD38. As antigen expression levels on plasma cells (PCs) were demonstrated to
      affect response to monoclonal antibody (mAb) treatment, a precise
      characterization of PC phenotype is warranted. METHODS: Anti-CD38 mAb
      (isatuximab) was tested for antibody-dependent cellular cytotoxicity (ADCC) in MM
      cell lines. Quantification of the number of sites (NOS) of CD38 on bone marrow
      PCs and other immune cells obtained from light chain (AL) amyloidosis (n = 46)
      and smoldering multiple myeloma (SMM) patients (n = 19) was performed with two
      different quantitative flow cytometry (QFCM) applications. RESULTS: ADCC activity
      of isatuximab was observed in cell lines with >100 * 103 CD38-NOS only. The
      average PC CD38-NOS was 153 +/- 53 * 103 in AL amyloidosis and 138.7 +/- 53 * 103
      in SMM patients. Eight (17%) AL amyloidosis and 4 (21%) SMM patients showed a PC
      CD38-NOS level <100 * 103 . In four AL amyloidosis and two SMM patients <10% of
      PCs had a CD38-NOS >=100 * 103 . The CD38-NOS identified on bone marrow
      lymphocytes, monocytes, and granulocytes was two log units below the CD38-NOS on
      PCs (P < 0.001). No significant differences in CD38-NOS expression levels on any
      of the analyzed PC subpopulations in AL amyloidosis and SMM patients were
      identified. CONCLUSION: Levels of CD38 expression affect the isatuximab-mediated
      ADCC in vitro. As PCs of patients with AL amyloidosis and SMM do not homogenously
      express high CD38 our data provide a rationale for assessment of CD38-NOS in
      patients with PC disorders prior to anti-CD38 treatment. (c) 2018 International
      Clinical Cytometry Society.

PMID- 29577601
TI  - The effects of cobalt and chromium ions on transforming growth factor-beta
      patterns and mineralization in human osteoblast-like MG63 and SaOs-2 cells.
AB  - Bone homeostasis, the balance of bone formation and resorption is affected by
      numerous influences, such as, hormones, inflammation, mechanical load, and
      external stimuli. The transforming growth factor-beta (TGF-beta), which exists in
      three isoforms in humans, is a major factor in the maintenance of this balance by
      regulating osteoblast and osteoclast maturation, development, and function. In
      artificial joint replacements, release of particles or ions from arthroplasties
      may exert local effects on the periprosthetic tissue and modulate the expression
      of bone specific genes and functions. Therefore, the influence of cobalt (II) and
      chromium (III) ions on the expression levels of the three TGF-beta isoforms in
      human osteosarcoma cell lines MG63 and SaOs-2 was analyzed and the impact on
      mineralization was studied. The osteosarcoma cell lines expressed all three TGF
      beta isoforms, with TGF-beta1 being the most abundant isoform. A dose dependent
      reduction of all TGF-beta isoforms by Co2+ ions was observed, the strongest
      effect was found on TGF-beta2. The effect was lesser pronounced in SaOs-2 cells.
      However, the Cr3+ ions had no significant effect on the expression of all TGF
      beta isoforms. In contrast, Co2+ ions in a concentration range of 50-250 uM did
      not impair the mineralization, but Cr3+ exerted a strong inhibitory effect on the
      mineralization in a dose dependent fashion. These data suggest that the influence
      of cobalt ions on bone homeostasis may in part result from the inhibitory effect
      on the transcription of the bone regulating cytokines TGF-beta1-3 whereas the
      chromium ions affect the process of mineralization. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 2105-2115, 2018.

PMID- 29577602
TI  - Lack of interferon-gamma attenuates foreign body reaction to subcutaneous
      implants in mice.
AB  - Subcutaneous implantation of synthetic materials and biomedical devices often
      induces abnormal tissue healing - the foreign body reaction-which impairs their
      function. In particular, Interferon-gamma (IFN-gamma) is a critical endogenous
      mediator of inflammation and plays a key role in a wide variety of biological
      responses including tissue healing. However, the contribution of endogenous IFN
      gamma on different features of the foreign body response induced by synthetic
      implants regarding neovascularization, inflammation, and fibrogenesis is not well
      known. Here, we evaluated inflammatory angiogenesis and fibrogenesis induced by
      implantation of polyether-polyurethane sponges in mice targeted disrupted of the
      interferon-gamma gene (IFN-gamma-/- ) and wild-type (WT). The hemoglobin content,
      the number of vessels, and blood flow (evaluated by LDPI-laser Doppler perfusion
      imaging) were decreased in the implants from IFN-gamma-/- as compared to WT mice.
      Likewise, neutrophils and macrophages accumulation (MPO and NAG activities,
      respectively) was decreased in IFN-gamma-/- implants. Interestingly, while the
      local content of VEGF, TNF-alpha, CXCL-1/KC, as measured by ELISA, and iNOS
      expression, as measured by qPCR, were significantly reduced, the content of IL-10
      was greatly increased in the implants from IFN-gamma-/- mice as compared to WT
      mice. No alterations were observed in CCL-2/MCP-1 levels. Lastly, the collagen
      deposition, assessed by Picro-Sirius red-stained histological sections, was also
      reduced in IFN-gamma-/- implants. Altogether, these data suggest that IFN-gamma
      activity contributes to inflammatory angiogenesis and fibrogenesis in synthetic
      implants and that lack of IFN-gamma expression attenuates foreign body reaction
      to implants in mice. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 2243-2250, 2018.

PMID- 29577603
TI  - Comparative analysis of respiratory motion tracking using Microsoft Kinect v2
      sensor.
AB  - PURPOSE: To present and evaluate a straightforward implementation of a marker
      less, respiratory motion-tracking process utilizing Kinect v2 camera as a gating
      tool during 4DCT or during radiotherapy treatments. METHODS: Utilizing the depth
      sensor on the Kinect as well as author written C# code, respiratory motion of a
      subject was tracked by recording depth values obtained at user selected points on
      the subject, with each point representing one pixel on the depth image. As a
      patient breathes, specific anatomical points on the chest/abdomen will move
      slightly within the depth image across pixels. By tracking how depth values
      change for a specific pixel, instead of how the anatomical point moves throughout
      the image, a respiratory trace can be obtained based on changing depth values of
      the selected pixel. Tracking these values was implemented via marker-less setup.
      Varian's RPM system and the Anzai belt system were used in tandem with the Kinect
      to compare respiratory traces obtained by each using two different subjects.
      RESULTS: Analysis of the depth information from the Kinect for purposes of phase-
      and amplitude-based binning correlated well with the RPM and Anzai systems.
      Interquartile Range (IQR) values were obtained comparing times correlated with
      specific amplitude and phase percentages against each product. The IQR time spans
      indicated the Kinect would measure specific percentage values within 0.077 s for
      Subject 1 and 0.164 s for Subject 2 when compared to values obtained with RPM or
      Anzai. For 4DCT scans, these times correlate to less than 1 mm of couch movement
      and would create an offset of 1/2 an acquired slice. CONCLUSION: By tracking
      depth values of user selected pixels within the depth image, rather than tracking
      specific anatomical locations, respiratory motion can be tracked and visualized
      utilizing the Kinect with results comparable to that of the Varian RPM and Anzai
      belt.

PMID- 29577604
TI  - Neurotrophin-3 released from implant of tissue-engineered fibroin scaffolds
      inhibits inflammation, enhances nerve fiber regeneration, and improves motor
      function in canine spinal cord injury.
AB  - Spinal cord injury (SCI) normally results in cell death, scarring, cavitation,
      inhibitory molecules release, etc., which are regarded as a huge obstacle to
      reconnect the injured neuronal circuits because of the lack of effective
      stimulus. In this study, a functional gelatin sponge scaffold was used to inhibit
      local inflammation, enhance nerve fiber regeneration, and improve neural
      conduction in the canine. This scaffold had good porosity and modified with
      neurotrophin-3 (NT-3)/fibroin complex, which showed sustained release in vitro.
      After the scaffold was transplanted into canine spinal cord hemisection model,
      hindlimb movement, and neural conduction were improved evidently. Migrating host
      cells, newly formed neurons with associated synaptic structures together with
      functional blood vessels with intact endothelium in the regenerating tissue were
      identified. Taken together, the results demonstrated that using bioactive
      scaffold could establish effective microenvironment stimuli for endogenous
      regeneration, providing a potential and practical strategy for treatment of
      spinal cord injury. (c) 2018 The Authors Journal of Biomedical Materials Research
      Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2158
      2170, 2018.

PMID- 29577605
TI  - Increased factor VIII plays a significant role in plasma hypercoagulability
      phenotype of patients with cirrhosis.
AB  - : Essentials The role of increased factor VIII in cirrhosis-induced
      hypercoagulability has never been demonstrated. Factor VIII and protein C effects
      were characterized by thrombin generation with thrombomodulin. Factor VIII
      elevation plays a significant role in cirrhosis-induced plasma
      hypercoagulability. Only protein C and factor VIII normalization led to thrombin
      generation similar to controls. SUMMARY: Background In cirrhosis, thrombin
      generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma
      hypercoagulability. Although the role of protein C (PC) deficiency has been
      investigated, the influence of an increase in the factor VIII level has never
      been addressed. Objectives We investigated the roles of high FVIII and low PC
      levels in increased TG in the presence of TM. Methods Blood samples were
      prospectively collected from 35 healthy controls and 93 patients with cirrhosis
      (Child-Turcotte-Pugh [CTP]-A, n = 61; CTP-B, n = 19; and CTP-C, n = 13) and FVIII
      levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with
      tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were
      normalized by adding an inhibitory anti-FVIII antibody and exogenous PC,
      respectively. Results The endogenous thrombin potential (ETP) in the presence of
      TM was higher in patients than in controls. After FVIII normalization, the ETP
      (median) decreased from 929 nm min to 621 nm min (CTP-A), 1122 nm min to 1082 nm
      min (CTP-B), and 1221 nm min to 1143 nm min (CTP-C); after PC normalization, it
      decreased from 776 nm min to 566 nm min (CTP-A), 1120 nm min to 790 nm min (CTP
      B), and 995 nm min to 790 nm min (CTP-C). The ETP was reduced by 17% and 30%,
      respectively, but normal TG was not restored. When both FVIII and PC levels were
      normalized, the ETP decreased from 929 nm min to 340 nm min (CTP-A), 1122 nm min
      to 506 nm min (CTP-B), and 1226 nm min to 586 nm min (CTP-C), becoming similar to
      control levels. Conclusion Cirrhosis-induced plasma hypercoagulability, as
      demonstrated in these experimental conditions, can be partly explained by
      opposite changes in two factors: PC level (decrease) and FVIII level (increase).

PMID- 29577607
TI  - Combinational drug delivery using nanocarriers for breast cancer treatments: A
      review.
AB  - Breast cancer (BC) is the most common cancer in women that requires special
      attention due to low response to conventional treatments. The common method for
      treating cancer (especially BC) is applying a single anticancer agent, however,
      due to some disadvantages including cytotoxicity, side effects, and multidrug
      resistance, the efficiency and application of this method are limited. To
      overcome these challenges, the combinational delivery of anticancer drugs
      (including chemical agents, genetic materials, etc.) has been introduced. To
      increase the efficacy of this new method, several nanocarriers including
      inorganic nanoparticles (such as, magnetic nanoparticles, silica nanoparticles,
      etc.) and organic ones (e.g., dendrimers, liposomes, micelles, and polymeric
      nanoparticles) have been used. Based on the literature, combinational delivery
      using nanocarriers showed promising results in the treatment of BC. In this
      review, combination regimens for the treatment of BC, nanocarriers containing
      combinations of pharmaceutical agents (including small molecule chemotherapeutic,
      biological, and gene therapy agents) as an opportunity to overcome chemotherapy
      challenges and, finally, examples of these formulations have been presented. This
      review aims to provide a better understanding of these increasingly important new
      methods of cancer treatment and the main issues and key considerations for a
      rational design of nanocarriers used in combinational delivery of different
      synergistic anticancer agents. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 2272-2283, 2018.

PMID- 29577606
TI  - A MMP7-sensitive photoclickable biomimetic hydrogel for MSC encapsulation towards
      engineering human cartilage.
AB  - Cartilage tissue engineering strategies that use in situ forming degradable
      hydrogels for mesenchymal stem cell (MSC) delivery are promising for treating
      chondral defects. Hydrogels that recapitulate aspects of the native tissue have
      the potential to encourage chondrogenesis, permit cellular mediated degradation,
      and facilitate tissue growth. This study investigated photoclickable
      poly(ethylene glycol) hydrogels, which were tailored to mimic the cartilage
      microenvironment by incorporating extracellular matrix analogs, chondroitin
      sulfate and RGD, and crosslinks sensitive to matrix metalloproteinase 7 (MMP7).
      Human MSCs were encapsulated in the hydrogel, cultured up to nine weeks, and
      assessed by mRNA expression, protein production and biochemical analysis.
      Chondrogenic genes, SOX9, ACAN, and COL2A1, significantly increased with culture
      time, and the ratios of COL2A1:COL10A1 and SOX9:RUNX2 reached values of ~20-100
      by week 6. The encapsulated MSCs degraded the hydrogel, which was nearly
      undetectable by week 9. There was substantial deposition of aggrecan and collagen
      II, which correlated with degradation of the hydrogel. Minimal collagen X was
      detectable, but collagen I was prevalent. After week 1, extracellular matrix
      elaboration was accompanied by a ~twofold increase in compressive modulus with
      culture time. The MMP7-sensitive cartilage mimetic hydrogel supported MSC
      chondrogenesis and promoted macroscopic neocartilaginous matrix elaboration
      representative of fibrocartilage. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 2344-2355, 2018.

PMID- 29577608
TI  - Impact of salvage treatment modalities in patients with positive FDG-PET/CT after
      R-CHOP chemotherapy for aggressive B-cell non-Hodgkin lymphoma.
AB  - INTRODUCTION: To compare outcomes of different salvage treatment modalities in
      patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET
      positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET
      primary refractory disease are limited. METHODS: Patients with diffuse large B
      cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from
      the Prince of Wales Hospital databases. Eligibility criteria were: age>=18 years,
      treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment
      modalities were: radical radiotherapy (RT, dose>=30 Gy), high dose chemotherapy
      and autologous stem cell transplant (ASCT), or non-radical management. Survival
      was calculated from date of post-chemotherapy FDG-PET to last follow-up. RESULTS:
      Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60
      (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24
      (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET
      positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in
      24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21
      (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non
      radical in five (20%). Median follow-up of surviving patients was 31 months.
      Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By
      salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical
      treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173).
      CONCLUSION: Patients with FDG-PET positive disease after R-CHOP for aggressive B
      cell NHL are salvageable with radiotherapy.

PMID- 29577609
TI  - The potential of the stem cells composite hydrogel wound dressings for promoting
      wound healing and skin regeneration: In vitro and in vivo evaluation.
AB  - In this study, the wound healing properties of the gelatin-based hydrogel (GBH)
      wound dressing combined with adipose-derived stem cells (ADSCs) were investigated
      using the mouse and porcine models. The analytical results showed that the ADSCs
      harvested from the porcine significantly increased cell growth and promoted cell
      differentiation (adipogenesis and osteogenesis) in comparison to the ADSCs
      harvested from the mouse in vitro. Moreover, the in vivo results also indicated
      that the GBH wound dressing combined with ADSCs and its culture medium could
      potentially accelerate wound healing in the mouse and porcine models. The ADSCs
      presented a possibility of recovery from wounds and injuries through skin
      regeneration. Therefore, both in vitro and in vivo results demonstrated that the
      ADSCs can potentially be an effective clinical treatment through the GBH wound
      dressing, which is a promising evidence-based complementary and alternative
      medicine for skin regeneration. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part B: Appl Biomater, 2018.

PMID- 29577610
TI  - Is postponed laparoscopic cholecystectomy justified for acute cholecystitis
      appearing early after onset?
AB  - INTRODUCTION: Early laparoscopic cholecystectomy (ELC) is considered the standard
      treatment for acute cholecystitis for patients who can tolerate surgery. The
      ideal time for performing ELC is reported to be 72 h from onset. However, many
      patients undergo surgery on or after the fourth day from onset, even if they
      presented early after onset. A few reports have investigated the feasibility and
      disadvantages of this so-called "postponed laparoscopic cholecystectomy" (PLC).
      METHODS: This study consisted of 215 patients who had undergone laparoscopic
      cholecystectomy for acute cholecystitis within 6 days of onset between July 2006
      and December 2017. Patients were divided into an ELC group (patients who
      underwent LC within 3 days of symptom onset, n = 172) and a PLC group (patients
      who underwent LC 4-6 days from symptom onset and on or after 3 days from
      admission, n = 43). Comparisons were made between these groups. RESULTS:
      Perioperative outcomes between the PLC and ELC groups were not significantly
      different, except for the requirement of subtotal cholecystectomy (SC) (16.2% vs
      5.2%, P = 0.013). In the PLC group, persistent fever after admission was
      significantly associated with the need for SC (P = 0.036). CONCLUSIONS: PLC for
      acute cholecystitis performed within 6 days of onset gave acceptable
      perioperative outcomes, except for an increased requirement for SC. Surgeons
      should keep in mind that PLC may increase the need for SC. A persistent fever
      after admission may be a risk factor for SC in the PLC group.

PMID- 29577611
TI  - SRARP and HSPB7 are epigenetically regulated gene pairs that function as tumor
      suppressors and predict clinical outcome in malignancies.
AB  - Deletions of chromosome 1p36 are common in cancers; however, despite extensive
      studies, there has been limited success for discovering candidate tumor
      suppressors in this region. SRARP has recently been identified as a novel
      corepressor of the androgen receptor (AR) and is located on chromosome 1p36.
      Here, bioinformatics analysis of large tumor datasets was performed to study
      SRARP and its gene pair, HSPB7. In addition, using cancer cell lines, mechanisms
      of SRARP and HSPB7 regulation and their molecular functions were investigated.
      This study demonstrated that SRARP and HSPB7 are a gene pair located 5.2 kb apart
      on 1p36.13 and are inactivated by deletions and epigenetic silencing in
      malignancies. Importantly, SRARP and HSPB7 have tumor suppressor functions in
      clonogenicity and cell viability associated with the downregulation of Akt and
      ERK. SRARP expression is inversely correlated with genes that promote cell
      proliferation and signal transduction, which supports its functions as a tumor
      suppressor. In addition, AR exerts dual regulatory effects on SRARP, and although
      an increased AR activity suppresses SRARP transcription, a minimum level of AR
      activity is required to maintain baseline SRARP expression in AR+ cancer cells.
      Furthermore, as observed with SRARP, HSPB7 interacts with the 14-3-3 protein,
      presenting a shared molecular feature between SRARP and HSPB7. Of note, genome-
      and epigenome-wide associations of SRARP and HSPB7 with survival strongly support
      their tumor suppressor functions. In particular, DNA hypermethylation, lower
      expression, somatic mutations, and lower copy numbers of SRARP are associated
      with worse cancer outcome. Moreover, DNA hypermethylation and lower expression of
      SRARP in normal adjacent tissues predict poor survival, suggesting that SRARP
      inactivation is an early event in carcinogenesis. In summary, SRARP and HSPB7 are
      tumor suppressors that are commonly inactivated in malignancies. SRARP
      inactivation is an early event in carcinogenesis that is strongly associated with
      worse survival, presenting potential translational applications.

PMID- 29577612
TI  - Physical validation of UF-RIPSA: A rapid in-clinic peak skin dose mapping
      algorithm for fluoroscopically guided interventions.
AB  - PURPOSE: The purpose of this study was to experimentally validate UF-RIPSA, a
      rapid in-clinic peak skin dose mapping algorithm developed at the University of
      Florida using optically stimulated luminescent dosimeters (OSLDs) and tissue
      equivalent phantoms. METHODS: The OSLDs used in this study were InLightTM Nanodot
      dosimeters by Landauer, Inc. The OSLDs were exposed to nine different beam
      qualities while either free-in-air or on the surface of a tissue equivalent
      phantom. The irradiation of the OSLDs was then modeled using Monte Carlo
      techniques to derive correction factors between free-in-air exposures and more
      complex irradiation geometries. A grid of OSLDs on the surface of a tissue
      equivalent phantom was irradiated with two fluoroscopic x ray fields generated by
      the Siemens Artis zee bi-plane fluoroscopic unit. The location of each OSLD
      within the grid was noted and its dose reading compared with UF-RIPSA results.
      RESULTS: With the use of Monte Carlo correction factors, the OSLD's response
      under complex irradiation geometries can be predicted from its free-in-air
      response. The predicted values had a percent error of -8.7% to +3.2% with a
      predicted value that was on average 5% below the measured value. Agreement within
      9% was observed between the values of the OSLDs and RIPSA when irradiated
      directly on the phantom and within 14% when the beam first traverses the tabletop
      and pad. CONCLUSIONS: The UF-RIPSA only computes dose values to areas of
      irradiated skin determined to be directly within the x ray field since the
      algorithm is based upon ray tracing of the reported reference air kerma value,
      with subsequent corrections for air-to-tissue dose conversion, x ray backscatter,
      and table/pad attenuation. The UF-RIPSA algorithm thus does not include the dose
      contribution of scatter radiation from adjacent fields. Despite this limitation,
      UF-RIPSA is shown to be fairly robust when computing skin dose to patients
      undergoing fluoroscopically guided interventions.

PMID- 29577613
TI  - Molecular biological analysis in a patient with multiple lung adenocarcinomas.
AB  - The utility of molecular biological analysis in lung adenocarcinoma has been
      demonstrated. Herein we report a rare case presenting as multiple lung
      adenocarcinomas with four different EGFR gene mutations detected in three lung
      tumors. After opacification was detected by routine chest X-ray, the patient, a
      64-year-old woman, underwent chest computed tomography which revealed a right
      lung segment S4 ground-glass nodule (GGN). Follow-up computed tomography revealed
      a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology
      of resected specimens from the right middle and lower lobes revealed all three
      nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors
      had the same mutations. Molecular biological analysis is a promising tool for the
      diagnosis of primary tumors in patients with multiple lung carcinomas of the same
      histotype, enabling appropriate treatment.

PMID- 29577614
TI  - Fully automated searching for the optimal VMAT jaw settings based on Eclipse
      Scripting Application Programming Interface (ESAPI) and RapidPlan knowledge-based
      planning.
AB  - PURPOSE: Eclipse treatment planning system has not been able to optimize the jaw
      positions for Volumetric Modulated Arc Therapy (VMAT). The arbitrary and planner
      dependent jaw placements define the maximum field size within which multi-leaf
      collimator (MLC) sequences can be optimized to modulate the beam. Considering the
      mechanical constraints of MLC transitional speed and range, suboptimal X jaw
      settings may impede the optimization or undermine the deliverability. This work
      searches optimal VMAT jaw settings automatically based on Eclipse Scripting
      Application Programming Interface (ESAPI) and RapidPlan knowledge-based planning.
      METHODS AND MATERIALS: Using an ESAPI script, the X jaws of rectal VMAT plans
      were initially set to conform the planning-target-volume (PTV), and were
      gradually extended toward the isocenter (PTV center) in 5-7 mm increments. Using
      these jaw pairs, 592 plans were automatically created for 10 patients and
      quantitatively evaluated using a comprehensive scoring function. A published
      RapidPlan model was evoked by ESAPI to generate patient-specific optimization
      objectives without manual intervention. All candidate plans were first stored as
      text files to save storage space, and only the best, worst, and conformal plans
      were consequently recreated for comparison. RESULTS: Although RapidPlan estimates
      dose-volume histogram (DVH) based on individual anatomy, the geometry-based
      expected dose (GED) algorithm does not recognize different jaw settings but uses
      PTV-conformal jaws as default; hence, identical DVHs were observed regardless of
      planner-defined jaws. Therefore, ESAPI finalized dose-volume calculation and
      eliminated the plans with unacceptable hotspots before comparison. The plan
      quality varied dramatically with different jaw settings. Trade-offs among
      different organs-at-risk (OARs) were collectively considered by the proposed
      scoring method, which identified the best and worst plans correctly. The plans
      using conformal jaws were neither the best nor the worst of all candidates.
      CONCLUSIONS: VMAT plans using optimal jaw locations can be created automatically
      using ESAPI and RapidPlan. Conformal jaws are not the optimal choice.

PMID- 29577615
TI  - Comparative pharmacokinetic study of the components of Jia-Wei-Kai-Xin-San in
      normal and vascular dementia rats by ultra-fast liquid chromatography coupled
      with tandem mass spectrometry.
AB  - A fast, sensitive, and reliable ultra-high performance liquid chromatography
      coupled with tandem mass spectrometry method has been developed and validated for
      simultaneous quantification of geniposide, polygalaxanthone III, 3,6'-disinapoyl
      sucrose, alpha-asarone, beta-asarone, poricoic acid A, poricoic acid B,
      dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma
      after oral administration of extracts of Jia-Wei-Kai-Xin-San in normal and
      vascular dementia rats. The developed method was precise and accurate within the
      linearity range of the analytes. The lower limits of quantification were 1.04
      2.68 ng/mL for all the analytes. Both intra- and inter day precision and accuracy
      of the analytes were all within accepted criteria. The mean extraction recoveries
      of the analytes and the internal standard from rat plasma were all >60.0%. The
      validated method had been successfully applied to compare pharmacokinetic
      profiles of the analytes in plasma of normal and vascular dementia rat treated
      with herbal extracts. Results indicated that differences existed between normal
      and vascular dementia model rats except dehydrotumulosic acid and kaempferide,
      which might be due to the pathology of vascular dementia and pharmacological
      effect of the analytes. These pharmacokinetic studies might benefit for the
      mechanism exploration and clinical use of traditional Chinese medicine formulae.

PMID- 29577616
TI  - Skating on thin ice: stimulant use and sub-optimal adherence to HIV pre-exposure
      prophylaxis.
AB  - INTRODUCTION: Stimulant and heavy alcohol use are prevalent and associated with
      elevated risk for HIV seroconversion among men who have sex with men (MSM) and
      transgender women. In addition, each can pose difficulties for antiretroviral
      adherence among people living with HIV. Scant research has examined the
      associations of stimulant and heavy alcohol use with adherence to daily oral pre
      exposure prophylaxis (PrEP) among MSM and transgender women. To address this gap
      in the literature, we evaluated the hypothesis that stimulant use and binge
      drinking are prospectively associated with sub-optimal PrEP adherence. METHODS:
      We analysed data from participants in a nested case-cohort in the iPrEx open
      label extension. Stimulant use (i.e. powder cocaine, crack-cocaine, cocaine
      paste, methamphetamine, cathinone) and binge drinking (i.e. >=5 drinks in a
      single day) in the last 30 days were assessed. Baseline urine was tested for
      stimulants using immunoassays to reduce misclassification. Sub-optimal adherence
      was defined as tenofovir drug concentrations in dried blood spots less than 700
      fmol per punch, indicative of less than four doses per week. We tested the
      prospective association of stimulant use and binge drinking with sub-optimal
      adherence at the 4-week follow-up visit. RESULTS AND DISCUSSION: Data from 330
      participants were analysed. The majority of the participants were MSM (89%) with
      a median age at baseline of 29 years (interquartile range 24 to 39).
      Approximately 16% (52/330) used stimulants and 22% (72/330) reported binge
      drinking in the last 30 days. Stimulant users had fivefold greater odds of sub
      optimal PrEP adherence compared to non-users in adjusted analysis (adjusted odds
      ratio [aOR] 5.04; [95% CI 1.35 to 18.78]). Self-reported binge drinking was not
      significantly associated with sub-optimal adherence after adjusting for stimulant
      use and baseline confounders (aOR 1.16 [0.49 to 2.73]). Depressive symptoms,
      being transgender, and number of sex partners were also not significantly
      associated with sub-optimal PrEP adherence (p > 0.05). CONCLUSIONS: Stimulant use
      is a risk factor for sub-optimal PrEP adherence in the month following PrEP
      initiation. Comprehensive prevention approaches that reduce stimulant use may
      optimize PrEP adherence. Creating adherence plans that specifically address PrEP
      dosing in the context of ongoing stimulant use should also be considered.

PMID- 29577617
TI  - A time-motion study of cardiovascular disease risk factor screening integrated
      into HIV clinic visits in Swaziland.
AB  - INTRODUCTION: Screening of modifiable cardiovascular disease (CVD) risk factors
      is recommended but not routinely provided for HIV-infected patients, especially
      in low-resource settings. Potential concerns include limited staff time and low
      patient acceptability, but little empirical data exists. As part of a pilot study
      of screening in a large urban HIV clinic in Swaziland, we conducted a time-motion
      study to assess the impact of screening on patient flow and HIV service delivery
      and exit interviews to assess patient acceptability. METHODS: A convenience
      sample of patients >=40 years of age attending routine HIV clinic visits was
      screened for hypertension, diabetes, hyperlipidemia and tobacco smoking. We
      observed HIV visits with and without screening and measured time spent on HIV and
      CVD risk factor screening activities. We compared screened and unscreened
      patients on total visit time and time spent receiving HIV services using Wilcoxon
      rank-sum tests. A separate convenience sample of screened patients participated
      in exit interviews to assess their satisfaction with screening. RESULTS: We
      observed 172 patient visits (122 with CVD risk factor screening and 50 without).
      Screening increased total visit time from a median (range) of 4 minutes (2 to 11)
      to 15 minutes (9 to 30) (p < 0.01). Time spent on HIV care was not affected: 4 (2
      to 10) versus 4 (2 to 11) (p = 0.57). We recruited 126 patients for exit
      interviews, all of whom indicated that they would recommend screening to others.
      CONCLUSION: Provision of CVD risk factor screening more than tripled the length
      of routine HIV clinic visits but did not reduce the time spent on HIV services.
      Programme managers need to take longer visit duration into account in order to
      effectively integrate CVD risk factor screening and counselling into HIV
      programmes.

PMID- 29577618
TI  - Flavan-3-ol/Procyanidin Metabolomics in Rat Urine Using HPLC-Quadrupole TOF/MS.
AB  - SCOPE: Several studies have demonstrated that flavan-3-ol/procyanidins are
      associated with biological functions in the prevention of various chronic
      diseases, including obesity and diabetes. Knowledge of their mechanisms,
      including bioavailability, has significantly progressed in the last decade.
      However, the differences of the metabolic signatures among flavan-3
      ol/procyanidins remain ambiguous. METHODS AND RESULTS: The metabolites in urine
      over time after acute administration of three typical flavan-3-ol/procyanidins
      ((epi)catechin [EPC], epigallocatechin gallate [EGCG], and procyanidin dimer
      [PC]) in view of the chemical structure were analyzed by HPLC-quadrupole TOF/MS.
      Several bile acid and amino acid derivatives including tryptophan and tyrosine,
      as well as flavan-3-ol/procyanidin conjugates and phenolic acid degradation
      products generated by the gut microbiota were observed in rat urine. CONCLUSION:
      Multivariate statistical analyses suggest that the exogenous and endogenous
      metabolites of flavan-3-ol/procyanidins greatly differ, although the chemical
      structures of three typical flavan-3-ol/procyanidins-EPC, EGCG, and PC-are
      similar. Thus, metabolomic differences likely affect their biological functions
      and health benefits.

PMID- 29577620
TI  - Erratum.

PMID- 29577619
TI  - Cellular and molecular mechanisms of vitamin D in food allergy.
AB  - Food allergies are becoming increasingly prevalent, especially in young children.
      Epidemiological evidence from the past decade suggests a role of vitamin D in
      food allergy pathogenesis. Links have been made between variations in sunlight
      exposure, latitude, birth season and vitamin D status with food allergy risk.
      Despite the heightened interest in vitamin D in food allergies, it remains
      unclear by which exact mechanism(s) it acts. An understanding of the roles
      vitamin D plays within the immune system at the cellular and genetic levels, as
      well as the interplay between the microbiome and vitamin D, will provide insight
      into the importance of the vitamin in food allergies. Here, we discuss the effect
      of vitamin D on immune cell maturation, differentiation and function; microbiome;
      genetic and epigenetic regulation (eg DNA methylation); and how these processes
      are implicated in food allergies.

PMID- 29577621
TI  - Strongly Coupled CoO Nanoclusters/CoFe LDHs Hybrid as a Synergistic Catalyst for
      Electrochemical Water Oxidation.
AB  - Exploiting high-performance, robust, and cost-effective electrocatalysts for the
      oxygen evolution reaction (OER) is crucial for electrochemical energy storage and
      conversion technologies. Engineering the interfacial structure of hybrid
      catalysts often induces synergistically enhanced electrocatalytic performance.
      Herein, a new strongly coupled heterogeneous catalyst with proper interfacial
      structures, i.e., CoO nanoclusters decorated on CoFe layered double hydroxides
      (LDHs) nanosheets, is prepared via a simple one-step pulsed laser ablation in
      liquid method. Thorough spectroscopic characterizations reveal that strong
      chemical couplings at the hybrid interface trigger charge transfer from CoII in
      the oxide to FeIII in the LDHs through the interfacial Fe?O?Co bond, leading to
      considerable amounts of high oxidation state CoIII sites present in the hybrid.
      Interestingly, the CoO/CoFe LDHs exhibit pronounced synergistic effects in
      electrocatalytic water oxidation, with substantially enhanced intrinsic catalytic
      activity and stability relative to both components. The hybrid catalyst achieves
      remarkably low OER overpotential and Tafel slope in alkaline medium,
      outperforming that of Ru/C and manifesting itself among the most active Co-based
      OER catalysts.

PMID- 29577622
TI  - Controllable Construction of Core-Shell Polymer@Zeolitic Imidazolate Frameworks
      Fiber Derived Heteroatom-Doped Carbon Nanofiber Network for Efficient Oxygen
      Electrocatalysis.
AB  - Designing rational nanostructures of metal-organic frameworks based carbon
      materials to promote the bifunctional catalytic activity of the oxygen reduction
      reaction (ORR) and oxygen evolution reaction (OER) is highly desired but still
      remains a great challenge. Herein, an in situ growth method to achieve 1D
      structure-controllable zeolitic imidazolate frameworks (ZIFs)/polyacrylonitrile
      (PAN) core/shell fiber (PAN@ZIFs) is developed. Subsequent pyrolysis of this
      precursor can obtain a heteroatom-doped carbon nanofiber network as an efficient
      bifunctional oxygen electrocatalyst. The electrocatalytic performance of derived
      carbon nanofiber is dominated by the structures of PAN@ZIFs fiber, which is
      facilely regulated by efficiently controlling the nucleation and growth process
      of ZIFs on the surface of polymer fiber as well as optimizing the components of
      ZIFs. Benefiting from the core-shell structures with appropriate dopants and
      porosity, as-prepared catalysts show brilliant bifunctional ORR/OER catalytic
      activity and durability. Finally, the rechargeable Zn-air battery assembled from
      the optimized catalyst (CNF@Zn/CoNC) displays a peak power density of 140.1 mW cm
      2 , energy density of 878.9 Wh kgZn-1 , and excellent cyclic stability over 150
      h, giving a promising performance in realistic application.

PMID- 29577623
TI  - HIV incidence among people who inject drugs in the Middle East and North Africa:
      mathematical modelling analysis.
AB  - INTRODUCTION: Emerging HIV epidemics have been documented among people who inject
      drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the
      HIV incidence among PWID due to sharing needles/syringes in MENA. It also
      delineates injecting drug use role as a driver of the epidemic in the population,
      and estimates impact of interventions. METHODS: A mathematical model of HIV
      transmission among PWID was applied in seven MENA countries with sufficient and
      recent epidemiological data and HIV prevalence >=1% among PWID. Estimations of
      incident and/or prevalent infections among PWID, ex-PWID and sexual partners of
      infected current and ex-PWID were conducted. RESULTS: The estimated HIV incidence
      rate for 2017 among PWID ranged between 0.7% per person-year (ppy) in Tunisia and
      7.8% ppy in Pakistan, with Libya being an outlier (24.8% ppy). The estimated
      number of annual new infections was lowest in Tunisia (n = 79) and Morocco (n =
      99), and highest in Iran and Pakistan (approximately n = 6700 each). In addition,
      20 to 2208 and 5 to 837 new annual infections were estimated across the different
      countries among sexual partners of PWID and ex-PWID respectively. Since epidemic
      emergence, the number of total ever acquired incident infections across countries
      was 706 to 90,015 among PWID, 99 to 18,244 among sexual partners of PWID, and 16
      to 4360 among sexual partners of ex-PWID. The estimated number of prevalent
      infections across countries was 341 to 23,279 among PWID, 119 to 16,540 among ex
      PWID, 67 to 10,752 among sexual partners of PWID, and 12 to 2863 among sexual
      partners of ex-PWID. Increasing antiretroviral therapy (ART) coverage to the
      global target of 81% - factoring in ART adherence and current coverage - would
      avert about half of new infections among PWID and their sexual partners.
      Combining ART with harm reduction could avert over 90% and 70% of new infections
      among PWID and their sexual partners respectively. CONCLUSIONS: There is
      considerable HIV incidence among PWID in MENA. Of all new infections ultimately
      due to injecting drug use, about 75% are among PWID and the rest among sexual
      partners. Of all prevalent infections ultimately attributed to injecting drug use
      as epidemic driver, about half are among PWID, 30% among ex-PWID and 20% among
      sexual partners of PWID and ex-PWID. These findings call for scale-up of services
      for PWID, including harm reduction as well as testing and treatment services.

PMID- 29577624
TI  - Attitudes toward early palliative care in cancer patients and caregivers: a
      Korean nationwide survey.
AB  - Integrated early palliative care (EPC) improves quality of life and reduces
      psychological distress in adult patients with cancer and caregivers, but
      attitudes toward EPC have been poorly studied. We aimed to investigate attitudes
      toward EPC in a nationwide survey of patients with cancer and caregivers. From
      July to October 2016, we administered nationwide questionnaires examining
      attitudes toward EPC in patients with cancer (n = 1001) and their families (n =
      1006) from 12 Korean hospitals. When an individual considered EPC unnecessary,
      the reasons were collected and analyzed. Factors associated with perception of
      EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had
      positive attitudes toward EPC. The most common reasons for deeming EPC
      unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%;
      caregivers: 23%; respectively) or that they were not sure if EPC is beneficial
      (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was
      more evident in caregivers (23%) than in patients (17%). Male gender, age <50,
      early stage, intensive care unit admission, and not believing that dying people
      should prepare to practice charity were associated with patients' negative
      attitudes. In caregivers, opposition to EPC was associated with not thinking
      death should be feared, not thinking people should be remembered, and lower
      educational level. Our findings showed that significant numbers of patients with
      advanced cancer and family caregivers showed positive attitudes toward EPC.
      However, more than 10% of participants did not consider EPC necessary.
      Physicians' communication with patients and caregivers and financial support
      could help overcome the barriers of EPC.

PMID- 29577625
TI  - In vivo blind-deconvolution photoacoustic ophthalmoscopy with total variation
      regularization.
AB  - Photoacoustic ophthalmoscopy (PAOM) is capable of noninvasively imaging anatomic
      and functional information of the retina in living rodents. However, the strong
      ocular aberration in rodent eyes and limited ultrasonic detection sensitivity
      affect PAOM's spatial resolution and signal-to-noise ratio (SNR) in in vivo eyes.
      In this work, we report a computational approach to combine blind deconvolution
      (BD) algorithm with a regularizing constraint based on total variation (BDTV) for
      PAOM imaging restoration. We tested the algorithm in retinal and choroidal
      microvascular images in albino rat eyes. The algorithm improved PAOM's lateral
      resolution by around 2-fold. Moreover, it enabled the improvement in imaging SNR
      for both major vessels and capillaries, and realized the well-preserved blood
      vessels' edges simultaneously, which surpasses conventional Richardson-Lucy BD
      algorithm. The reported results indicate that the BDTV algorithm potentially
      facilitate PAOM in extracting retinal pathophysiological information by enhancing
      in vivo imaging quality without physically modifying PAOM's optical
      configuration.

PMID- 29577626
TI  - Alcohol-Soluble Electron-Transport Materials for Fully Solution-Processed Green
      PhOLEDs.
AB  - Two alcohol-soluble electron-transport materials (ETMs), diphenyl(4-(1-phenyl-1H
      benzo[d]imidazol-2-yl)phenyl)phosphine oxide (pPBIPO) and (3,5-bis(1-phenyl-1H
      benzo[d]imidazol-2-yl)phenyl)diphenylphosphine oxide (mBPBIPO), have been
      synthesized. The physical properties of these ETMs were investigated and they
      both exhibited high electron-transport mobilities (1.67*10-4 and 2.15*10-4  cm2 
      V-1  s-1 ), high glass-transition temperatures (81 and 110  degrees C), and low
      LUMO energy levels (-2.87 and -2.82 eV, respectively). The solubility of PBIPO in
      n-butyl alcohol was more than 20 mg mL-1 , which meets the requirement for fully
      solution-processed organic light-emitting diodes (OLEDs). Fully solution
      processed green-phosphorescent OLEDs were fabricated by using alcohol-soluble
      PBIPO as electron-transport layers (ETLs), and they exhibited high current
      efficiencies, power efficiencies, and external quantum efficiencies of up to
      38.43 cd A-1 , 26.64 lm W-1 , and 10.87 %, respectively. Compared with devices
      that did not contain PBIPO as an ETM, the performance of these devices was much
      improved, which indicated the excellent electron-transport properties of PBIPO.

PMID- 29577627
TI  - Review article: Investigations and the pregnant woman in the emergency department
      - part 2: Point-of-care ultrasound, electrocardiography, respiratory function
      tests and radiology.
AB  - Accurate assessment of the pregnant patient in the ED depends on knowledge of
      physiological changes in pregnancy, and how these changes may impact on pathology
      tests, appearance on point-of-care ultrasound, electrocardiography and
      respiratory function tests. In addition, the emergency physician needs to be
      cognisant of disorders that are unique to or more common during pregnancy. Part 2
      of this review addresses the role of point-of-care ultrasound in pregnancy,
      physiological changes that may affect interpretation of point-of-care ultrasound,
      changes in electrocardiography and respiratory function tests, and the safety of
      radiological procedures in the pregnant patient. Part 1 addressed potential
      deviations in laboratory investigation reference intervals resulting from
      physiological alterations in pregnancy and the important causes of abnormal
      laboratory results in pregnancy.

PMID- 29577628
TI  - Self-reported skin concerns: An epidemiological study of community-dwelling older
      people.
AB  - AIM: To identify the frequency and impact of self-reported skin concerns in
      community-dwelling older people. BACKGROUND: Globally, the population is getting
      older and it is essential to develop effective interventions to promote healthy
      ageing. Skin change with age is inevitable and renders this often neglected organ
      more vulnerable to damage and breakdown; this can be costly to individuals and
      society. Maintenance of skin health in older people presents a health challenge
      that has yet to be fully understood or addressed. METHODS: Cross-sectional, self
      reported questionnaire survey in England. Patients registered with participating
      general practices (n = 3), aged >=70 years, living in their own homes and able to
      give informed consent (n = 3,359) were sent a letter of invitation to a free
      health and care assessment, and 1116 responded. RESULTS: When asked "do you have
      any concerns about your skin?", 16.5% (n = 183) said yes. Of this group, the most
      common concerns were dry skin 80.7% (n = 146), itching 56.9% (n = 103) and aged
      appearance 61% (n = 113). Itch, dry skin and inflammation were rated as most
      bothersome. There was a significant association between the dry skin and itch
      chi2 (1) = 6.9, p < .05. CONCLUSION: Many community-dwelling older people suffer
      from skin concerns predominantly dry skin and itching that is often bothersome.
      IMPLICATIONS FOR PRACTICE: Skin health assessment is often absent in routine
      consultations with community-dwelling older people. Dry, itchy skin is prevalent
      and can be simply managed with low-cost interventions. This has the potential to
      reduce suffering and maintain or improve skin barrier function. Nurses and other
      health professionals should therefore routinely assess and advise on skin health
      care for this population.

PMID- 29577629
TI  - Efficacy and safety of intravitreal anti-tumour necrosis factor drugs in adults
      with non-infectious uveitis - a systematic review.
AB  - Anti-tumour necrosis factor (TNF) drugs have been extensively used in non
      infectious uveitis (NIU), when corticosteroids or conventional immunosuppressive
      drugs cannot adequately control inflammation or intolerable side-effects occur.
      However, systemic anti-TNF therapies are also associated with a myriad of side
      effects. Therefore, intravitreal administration of anti-TNF biologics has been
      employed to minimize patient morbidity and systemic adverse effects, while
      maintaining therapeutic effectivity. We undertook a systematic review to
      determine evidence of efficacy and safety of intravitreal administration of anti
      TNF drugs in adults with NIU. We conducted this systematic review according to
      the PRISMA guidelines. The protocol was registered with PROSPERO
      (CRD42016041946). We searched CENTRAL, MEDLINE and EMBASE, from inception to
      April 2017, as well as clinical trial registries and grey literature. The
      qualitative analysis included all studies of adult patients with a diagnosis of
      NIU and who received intravitreal anti-TNF drugs with a 4-week minimum follow-up.
      A total of 4840 references were considered for title and abstract screening.
      Seven full texts were screened, and five studies were considered for analysis.
      All studies were open-label, single-centre, prospective, non-randomized,
      interventional case series with a follow-up between 4 and 26 weeks, employing
      either adalimumab in two studies and infliximab in three. Three studies showed a
      treatment effect of anti-TNF intravitreal injections, while one study revealed
      short-term improvement and one study revealed no efficacy of anti-TNF
      intravitreal therapy. None of the studies reported ocular adverse effects but
      only two studies included electrophysiological assessment in the safety analysis
      and no study assessed systemic human anti-drug antibodies. The available evidence
      is not sufficiently robust to conclude about the clinical effectivity of
      intravitreal anti-TNF in NIU and so no recommendation can be made. In conclusion,
      intravitreal injection of anti-TNF antibodies remains a possible treatment option
      to be explored through robust clinical investigation.

PMID- 29577630
TI  - Diagnostic accuracy of diffusion-weighted imaging- magnetic resonance imaging
      compared to positron emission tomography/computed tomography in evaluating and
      assessing pathological response to treatment in adult patients with lymphoma: A
      systematic review.
AB  - The use of Positron emission tomography/computerised tomography (PET/CT) is well
      established in the staging and assessment of treatment response of lymphoma.
      Recent studies have suggested that whole body diffusion-weighted imaging 
      magnetic resonance imaging (WB-DW-MRI) may be an alternative to PET/CT in both
      staging and assessment of treatment response. A systematic review was performed
      to assess the ability of DW-MRI in the assessment of treatment response in
      lymphoma. Pubmed, Medline, Web of Science and Embase databases were queried for
      studies examining whole body DW-MRI compared to PET/CT in adult patients using a
      protocol of search terms. We carried out an extensive assessment of titles,
      abstracts and full texts of relevant paper as well as quality assessment with the
      Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. Eight studies were
      found to meet the criteria and were included in our review and analysis. Overall,
      the quality of studies was found to be moderate, with good inter-rater agreement
      (K = 0.74). Data analysis showed that lesion-based assessment in 5 studies with
      pooled results had a sensitivity and specificity of 94.7% and 99.3%. Assessment
      with Cohen's Kappa coefficient showed agreement to be excellent (K = 0.88). Three
      studies were included for qualitative analysis, two of which showed good
      equivalence between PET/CT and DW-MRI. WB-DWI-MRI can be considered a sensitive
      and specific method for assessing treatment response in Lymphoma without the use
      of ionising radiation or administration of F-18 Flurodeoxyglucose. Further
      studies are needed to evaluate the optimum b-values in assessing treatment
      response.

PMID- 29577631
TI  - The regulatory mechanism of mammalian TRPMLs revealed by cryo-EM.
AB  - Transient receptor potential mucolipin (TRPML) channels are the most recently
      identified subfamily of TRP channels and have seen a surge of new reports
      revealing both structural and functional insight. In 2017, several groups
      published multiple conformations of TRPML channels using cryo-EM. Similar to
      other TRP channels, the ML subfamily consists of six transmembrane helices (S1
      S6), and a pore region including S5, S6, and two pore helices (PH1 and PH2).
      However, these reports also reveal distinct structural characteristics of the ML
      subfamily. Asp residues within the luminal pore may function to control
      calcium/pH regulation. A synthetic agonist, ML-SA1, can bind to the pore region
      of TRPMLs to force a direct dilation of the lower gate. Finally, biophysical and
      electrophysiological characterizations reveal another natural agonist binding
      site in the unique domain of TRPMLs, presumably regulating the conformation of
      the S4-S5 linker to open the channel. This work elucidates the molecular
      architecture and provides insights into how multiple ligands regulate TRPMLs.

PMID- 29577632
TI  - Interleukin-2 receptor antagonists: Protective factors against new-onset diabetes
      after renal transplantation.
AB  - BACKGROUND: The aim of the present study was to examine the association between
      interleukin-2 receptor antagonists (IL-2Ra) and new-onset diabetes after
      transplantation (NODAT) among renal transplant recipients (RTRs). METHODS:
      Between January 1993 and March 2014, 915 patients underwent renal transplantation
      at Zhongshan Hospital. In all, 557 RTRs were included in the present
      retrospective cohort study. The incidence of NODAT in this cohort was determined
      and multivariate Cox regression analysis was used to evaluate the risk factors
      for NODAT and to show the association between IL-2Ra use and NODAT development
      among RTRs. The cumulative incidence of NODAT was compared between groups treated
      with or without IL-2Ra. RESULTS: The mean +/-SD postoperative follow-up was 5.08
      +/-3.17 years. The incidence of NODAT at the end of follow-up was 20.3%. After
      adjusting for potential confounders in the multivariate logistic regression (i.e.
      age, sex, body mass index, history of smoking, family history of diabetes,
      duration of dialysis, type of dialysis, donor type, recovery of graft function,
      acute rejection, hepatitis B or C or cytomegalovirus infection, fasting plasma
      glucose levels before and 1 week after transplantation, preoperative total
      cholesterol and triglyceride levels, daily dose of glucocorticoid,
      immunosuppressive regimen type, and immunosuppressant concentration after
      transplantation), IL-2Ra use was found to be related to a reduced incidence of
      NODAT. CONCLUSIONS: Use of IL-2Ra is associated with protection against the
      development of NODAT in RTRs.

PMID- 29577633
TI  - Impact of pediatric cancer on family relationships.
AB  - Little is known about the impact of cancer on family relationships from the
      perspective of the pediatric cancer patient and their sibling(s). This study
      assessed and compared children's experiences of family relationships in patients
      receiving active cancer therapy, those who have completed therapy, and siblings.
      A cross-sectional study of children with cancer and their siblings aged 8-17
      years old was conducted. Children completed the PROMIS Pediatric Family
      Relationships short form and the Depressive Symptoms, Anxiety, and Peer
      Relationships short forms. The Mann-Whitney test assessed differences in Family
      Relationships scores between therapy groups, while the Wilcoxon signed-rank test
      assessed differences between patients and siblings. An actor-partner
      interdependence model (APIM) was used to assess how patient and sibling variables
      were associated with their own and each others' family relationships. Two hundred
      and sixty-five children completed the assessments. Siblings of patients on
      therapy had worse family relationships than patients on-therapy (P = 0.015).
      Family relationships of patients off-therapy did not differ from their siblings
      or the patients on-therapy. Family relationships scores did not differ between
      the sibling cohorts. The APIM found patient family relationships were impaired
      when their own peer relationships decreased and when either their own or their
      siblings had increased depressive symptoms. Sibling family relationships were
      impaired when their own depression increased, and when the patient counterpart
      was female, younger age, had less depressive symptoms, more anxiety or a
      diagnosis of leukemia/lymphoma (compared to solid tumor). Based on these
      findings, increased psychosocial resources for patients and siblings of children
      undergoing cancer therapy may be warranted.

PMID- 29577634
TI  - Molecular epidemiology of Shiga toxin-producing O113:H21 isolates from cattle and
      meat.
AB  - The serotype O113:H21 is considered one of the relevant non-O157 STEC serotypes
      associated with severe human infections. Due to the increased detection of O113
      strains and their relationship with clinical cases, which emphasizes the
      importance of this serogroup as an emerging pathogen, our aim was to determine
      the characteristics of STEC O113:H21 strains circulating in bovine cattle and
      retail meat from Argentina. For this purpose, we determined the presence and
      combinations of various virulence genes (and their variants) related to adhesion
      and toxicity in a collection of 34 isolates. Their genetic relatedness using
      multiple-locus variable-number tandem repeat analysis (MLVA) was also studied.
      Subtyping of stx genes indicated that O113:H21 strains circulating in Argentina
      mainly present stx2a alone or together with stx2c or, less frequent, with stx2d ,
      all of which are subtypes associated with human disease. We found plasmid
      markers, such as saa, ehxA and subA, in a higher proportion than previous
      studies, and five variants of saa, two of which were novel ones. In relation to
      MLVA subtyping, we detected a limited diversity among the isolates considering
      that several loci were not discriminative and, that in some farms, the same clone
      seemed to remain circulating throughout the year. The O113:H21 strains studied
      harbour several toxin and adhesion genes (saa, espP, fimCD, ehaA, iha, hcpA,
      elfA, lpfO113, ecpA, subA, cdt-V) and Stx subtypes associated with human disease.
      Results also highlighted that subtyping of stx and saa is useful to discriminate
      O113:H21 strains that share virulence genes. In conclusion, this study shows that
      a number of O113:H21 strains that occur in foods and bovines could be pathogenic
      for humans. This situation calls for further attention in the prevention and
      control of foodborne disease caused by these strains.

PMID- 29577635
TI  - Carbon Monoxide-Releasing Molecule Enhances Coagulation and Decreases
      Fibrinolysis in Normal Canine Plasma.
AB  - The dog is an important companion animal and also purpose-bred for research
      studies. Coagulopathies in dogs are common, although the availability of blood
      products for therapy is inconsistent throughout the profession. A pro-coagulant
      therapeutic that is readily available and easily stored would be useful for the
      treatment of coagulopathies. Tricarbonyldichlororuthenium (II) dimer [Carbon
      monoxide-releasing molecule-2 (CORM-2)] acts as a prothrombotic agent in plasma
      by increasing the velocity of clot formation and clot strength, and by decreasing
      the clot's vulnerability to fibrinolysis. We sought to test CORM-2's effect on
      coagulation and fibrinolysis in vitro in canine plasma using thromboelastography.
      Measures of the rate of clot formation and clot strength in plasma without CORM-2
      were highly correlated with fibrinogen concentration. We found that CORM-2
      significantly enhanced the rate of clot formation and clot strength and
      significantly reduced the rate of fibrinolysis and the clot lysis time. The per
      cent change in rate of clot formation and clot strength was not significantly
      correlated with fibrinogen concentration, indicating that CORM-2's pro-coagulant
      effect is not dependent on fibrinogen concentration. This study corroborates
      studies in other species that show that CORM-2 is pro-coagulant in plasma, and
      lays the groundwork for developing CORM-2 as a therapeutic agent for canine
      coagulopathies. Future studies will evaluate the effect of CORM-2 on whole blood
      both in vitro and in vivo.

PMID- 29577636
TI  - Time-lapse microscopy of oxidative stress demonstrates metabolic sensitivity of
      retinal pericytes under high glucose condition.
AB  - Hyperglycemia affects retinal vascular cell function, promotes the development
      and progression of diabetic retinopathy and ultimately causes vision loss.
      Oxidative stress, reactive oxygen species (ROS) in excess, is a key biomarker for
      diabetic retinopathy. Using time-lapse fluorescence microscopy, ROS dynamics was
      monitored and the metabolic resistivity of retinal endothelial cells (REC) and
      pericytes (RPC) was compared under metabolic stress conditions including high
      glucose (HG). In the presence of a mitochondrial stressor, REC exhibited a
      significant increase in the rate of ROS production compared with RPC. Thus, under
      normal glucose (NG), REC may utilize oxidative metabolism as the bioenergetic
      source, while RPC metabolic activity is independent of mitochondrial respiration.
      In HG condition, the rate of ROS production in RPC was significantly higher,
      whereas this rate remained unchanged in REC. Thus, under HG condition RPC may
      preferentially utilize oxidative metabolism, which results in increased rate of
      ROS production. In contrast, REC use glycolysis as their major bioenergetic
      source for ATP production, and consequently HG minimally affects their ROS
      levels. These observations are consistent with our previous studies where we
      showed HG condition has minimal effect on apoptosis of REC, but results in
      increased rate of apoptosis in RPC. Collectively, our results suggest that REC
      and RPC exhibit different metabolic activity preferences under different glucose
      conditions. Thus, protection of RPC from oxidative stress may provide an early
      point of intervention in development and progression of diabetic retinopathy.

PMID- 29577637
TI  - Patient's perspective on long-term complications after superficial parotidectomy
      for benign lesions: Prospective analysis of a 2-year follow-up.
AB  - OBJECTIVE: Evaluation of patients' perspective on long-term complications after
      superficial parotidectomy for benign lesions. DESIGN: A prospective nonrandomized
      controlled multicenter study. SETTING: Three university-based tertiary referral
      centers (Departments of Otorhinolaryngology of Cologne, Jena and Giessen; all in
      Germany). PARTICIPANTS: 130 adult patients, who underwent a primary superficial
      parotidectomy for benign tumors of the parotid gland, were consecutively included
      from 09/2010 to 05/2012. 61 patients completed every follow-up examination. MAIN
      OUTCOME MEASURES: Complications were evaluated using the validated German
      language questionnaire Parotidectomy Outcome Inventory 8 at six, 12 and 24 months
      after surgery. Pain intensity was assessed on a numeric rating scale (NRS) at
      each follow-up visit. RESULTS: At 6 months after surgery, 90% characterized
      hypoesthesia as the most disturbing problem, followed by fear of revision surgery
      (57%) and scar (56%). Facial palsy (14%) posed the minor problem. Hypoesthesia
      improved significantly during the follow-up period (all P < .05), but still posed
      a problem for 78% of the patients after 2 years. Pain, which initially bothered
      53% of the patients, significantly decreased, whereas impairment due to Frey's
      syndrome significantly increased during the follow-up (6 vs 24 months; P = .002
      and P = .001, respectively). Scar, substance loss, xerostomia, facial palsy, and
      anxiety affected patients with unvarying severity during the 2 years (all P >
      .05). CONCLUSIONS: From patients' perspective, sensation loss posed the major
      subjective problem after superficial parotidectomy. Appearance of the scar, and
      fear of revision surgery impaired more than 50% of the patients in their daily
      life without significant improvement during the 2 years postoperatively. Although
      superficial parotidectomy is a highly standardized and safe procedure, limited
      parotidectomy for proven benign parotid salivary gland neoplasms is more likely
      to result in patients with minimal or no displeasing complications.

PMID- 29577638
TI  - Upregulation of CXCR4 through promoter demethylation contributes to inflammatory
      hyperalgesia in rats.
AB  - AIM AND METHODS: Chronic pain associated with inflammation is a common clinical
      problem, and the underlying mechanisms yet are incompletely defined. DNA
      methylation has been implicated in the pathogenesis of chronic pain. However, the
      specific genes regulated by DNA methylation under inflammatory pain condition
      remain largely unknown. Here, we investigated how chemokine receptor CXCR4
      expression is regulated by DNA methylation and how it contributes to inflammatory
      pain induced by complete Freund's adjuvant (CFA) in rats. RESULTS: Intraplantar
      injection of CFA could not only induce significant hyperalgesia in rats, but also
      significantly increase the expression of CXCR4 mRNA and protein in the dorsal
      root ganglion (DRG). Intrathecal injection of CXCR4 antagonist AMD3100
      significantly relieved hyperalgesia in inflammatory rats in a time- and dose
      dependent manner. Bisulfite sequencing and methylation-specific PCR demonstrate
      that CFA injection led to a significant demethylation of CpG island at CXCR4 gene
      promoter. Consistently, the expression of DNMT3b was significantly downregulated
      after CFA injection. Online software prediction reveals three binding sites of
      p65 in the CpG island of CXCR4 gene promoter, which has confirmed by the
      chromatin immunoprecipitation assay, CFA treatment significantly increases the
      recruitment of p65 to CXCR4 gene promoter. Inhibition of NF-kB signaling using
      p65 inhibitor pyrrolidine dithiocarbamate significantly prevented the increases
      of the CXCR4 expression. CONCLUSION: Upregulation of CXCR4 expression due to
      promoter demethylation followed by increased recruitment of p65 to promoter of
      CXCR4 gene contributes to inflammatory hyperalgesia. These findings provide a
      theoretical basis for the treatment of chronic pain from an epigenetic
      perspective.

PMID- 29577639
TI  - A novel rapid quantitative method reveals stathmin-1 as a promising marker for
      esophageal squamous cell carcinoma.
AB  - Stathmin-1 is a microtubule depolymerization protein that regulates cell
      division, growth, migration, and invasion. Overexpression of stathmin-1 has been
      observed to be associated with metastasis, poor prognosis, and chemoresistance in
      various human cancers. Our previous studies found that serum stathmin-1 was
      significantly elevated in patients with esophageal squamous cell carcinoma (ESCC)
      by ELISAs. Here, we constructed high-affinity monoclonal antibodies and then
      developed a competitive AlphaLISA for rapid, accurate quantitation of stathmin-1
      in serum. Compared to ELISA, our homogeneous AlphaLISA showed better sensitivity
      and accuracy, a lower limit of detection, and a wider linear range. The
      measurements of nearly 1000 clinical samples showed that serum stathmin-1 level
      increased dramatically in patients with squamous cell carcinoma (SCC), especially
      in ESCC, with a sensitivity and a specificity of 81% and 94%, respectively. Even
      for early stage ESCC, stathmin-1 achieved an area under the receiver operating
      characteristic curve (AUC) of 0.88. Meanwhile, raised concentrations of stathmin
      1 were associated with lymph node metastasis and advanced cancer stage. Notably,
      various types of SCC showed significantly higher AUCs in serum stathmin-1
      detection compared to adenocarcinoma. Furthermore, we confirmed that stathmin-1
      was enriched in the oncogenic exosomes, which can explain the reason why it
      enters into the blood to serve as a tumor surrogate. In conclusion, this large
      scale and systematic study of serum stathmin-1 measured by our newly established
      AlphaLISA showed that stathmin-1 is a very promising diagnostic and predictive
      marker for SCC in the clinic, especially for ESCC.

PMID- 29577640
TI  - A Kv1.3 channel-specific blocker alleviates neurological impairment through
      inhibiting T-cell activation in experimental autoimmune encephalomyelitis.
AB  - AIM: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized
      by mistaken attacks of inflammatory cells against the central nervous system
      (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can
      inhibit T-cell activation and have been designed for MS therapy. However, little
      is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons
      in MS. This study aimed at investigating the neuroprotection efficacy of a
      selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model. METHODS:
      Experimental autoimmune encephalomyelitis (EAE) rat model was established. The
      neuroprotective effect of ImK was assessed by immunohistochemistry and
      transmission electron microscopy (TEM). In addition, the antiinflammatory effect
      of ImK by suppressing T-cell activation was assessed by flow cytometry and ELISA
      in vitro. RESULTS: Our results demonstrated that ImK administration ameliorated
      EAE clinical severity. Moreover, ImK increased oligodendrocytes survival,
      preserved axons, and myelin integrity and reduced the infiltration of activated T
      cells into the CNS. This protective effect of the peptide may be related to its
      suppression of autoantigen-specific T-cell activation via calcium influx
      inhibition. CONCLUSION: ImK prevents neurological damage by suppressing T-cell
      activation, suggesting the applicability of this peptide in MS therapy.

PMID- 29577641
TI  - Anthropometric Indices Based on Waist Circumference as Measures of Adiposity in
      Children.
AB  - OBJECTIVE: The aim of this study was to compare the accuracy of body fat patterns
      and single measures in assessing body fat and to clarify the use of indices based
      on waist circumference as measures of adiposity in children. METHODS: This study
      included 2,531 7-year-old children from the Generation XXI birth cohort (Porto,
      Portugal). Anthropometrics were obtained by trained personnel and whole-body dual
      energy x-ray absorptiometry (DXA) scans were performed. RESULTS: Principal
      component analysis identified two body fat patterns. Pattern 1 (BMI, fat mass
      index from tetra-polar bioelectric impedance, and waist-to-height ratio) showed
      strong correlations with DXA fat mass index (r = 0.85; P < 0.001), and pattern 2
      (waist-to-hip, waist-to-thigh, and waist-to-weight ratios) showed moderate
      correlations with DXA central fat (r = 0.35; P < 0.001). Compared with single
      measures, body fat patterns showed similar correlations with DXA-derived
      measures. CONCLUSIONS: Compared with single anthropometric indices, body fat
      patterns seem to add little value for estimating body fat in children. Waist-to
      height ratio seems to be a proxy for total fat, while waist-to-hip, waist-to
      thigh, and waist-to-weight ratios seem to be proxies for central fat. Further
      studies should address the predictive ability of waist-to-weight ratio to
      identify children at risk of developing cardiometabolic disease, as this was the
      first time describing its potential usefulness.

PMID- 29577642
TI  - A simple, fast, and accurate thermodynamic-based approach for transfer and
      prediction of GC retention times between columns and instruments Part II:
      Estimation of target column geometry.
AB  - The transfer of thermodynamic parameters governing retention of a molecule in gas
      chromatography from a reference column to a target column is a difficult problem.
      Successful transfer demands a mechanism whereby the column geometries of both
      columns can be determined with high accuracy. This is the second part in a series
      of three papers. In Part I of this work we introduced a new approach to determine
      the actual effective geometry of a reference column and thermodynamic-based
      parameters of a suite of compounds on the column. Part II, presented here,
      illustrates the rapid estimation of the effective inner diameter (or length) and
      the effective phase ratio of a target column. The estimation model based on the
      principle of least squares; a fast Quasi-Newton optimization algorithm was
      developed to provide adequate computational speed. The model and optimization
      algorithm were tested and validated using simulated and experimental data. This
      study, together with the work in Parts I and III, demonstrates a method that
      improves the transferability of thermodynamic models of gas chromatography
      retention between gas chromatography columns.

PMID- 29577643
TI  - Susceptibilities of Candidatus Liberibacter asiaticus-infected and noninfected
      Diaphorina citri to entomopathogenic fungi and their detoxification enzyme
      activities under different temperatures.
AB  - Some entomopathogenic fungi species, Isaria fumosorosea, and Hirsutella
      citriformis were found to be efficient against the Asian citrus psyllid,
      Diaphorina citri Kuwayama (Hemiptera: Liviidae). However, the susceptibility to
      these fungi increases when the psyllid infected with Candidatus Liberibacter
      asiaticus (Las), which is transmitted by D. citri and causes citrus greening
      disease. In this study, we examined the Las-infected and Las-uninfected D. citri
      susceptibility to entomopathogenic fungi at different temperature regimes (5-40
      degrees C). When D. citri adults exposed to cold temperature (5 degrees C), they
      showed less susceptibility to entomopathogenic fungi as compared with control (27
      degrees C). Irrespective of infection with Las, a significantly positive
      correlation was observed between temperature and percentage mortality caused by
      different isolates of I. fumosorosea, 3A Ifr, 5F Ifr, PS Ifr, and H. citriformis
      isolates, HC3D and 2H. In contrast, a significantly negative correlation was
      found between temperature and percentage mortality for 3A Ifr for both Las
      infected and Las-uninfected psyllids. Detoxification enzymes, Glutathione S
      transferase levels in D. citri showed a negative correlation, whereas cytochrome
      P450 and general esterase levels were not correlated with changes in temperature.
      These findings revealed that detoxification enzymes and general esterase levels
      are not correlated with altered susceptibility to entomopathogenic fungi at the
      different temperature regimes. Conclusively, temperature fluctuations tested
      appear to be a significant factor impacting the management strategies of D. citri
      using entomopathogenic fungi.

PMID- 29577644
TI  - Systematic Evaluation of Immobilized Trypsin-Based Fast Protein Digestion for
      Deep and High-Throughput Bottom-Up Proteomics.
AB  - Immobilized trypsin (IM) has been recognized as an alternative to free trypsin
      (FT) for accelerating protein digestion 30 years ago. However, some questions of
      IM still need to be answered. How does the solid matrix of IM influence its
      preference for protein cleavage and how well can IM perform for deep bottom-up
      proteomics compared to FT? By analyzing Escherichia coli proteome samples
      digested with amine or carboxyl functionalized magnetic bead-based IM (IM-N or IM
      C) or FT, it is observed that IM-N with the nearly neutral solid matrix, IM-C
      with the negatively charged solid matrix, and FT have similar cleavage preference
      considering the microenvironment surrounding the cleavage sites. IM-N (15 min)
      and FT (12 h) both approach 9000 protein identifications (IDs) from a mouse brain
      proteome. Compared to FT, IM-N has no bias in the digestion of proteins that are
      involved in various biological processes, are located in different components of
      cells, have diverse functions, and are expressed in varying abundance. A high
      throughput bottom-up proteomics workflow comprising IM-N-based rapid protein
      cleavage and fast CZE-MS/MS enables the completion of protein sample preparation,
      CZE-MS/MS analysis, and data analysis in only 3 h, resulting in 1000 protein IDs
      from the mouse brain proteome.

PMID- 29577645
TI  - A novel monoclonal antibody KMP1 has potential antitumor activity of bladder
      cancer by blocking CD44 in vivo and in vitro.
AB  - Bladder cancer becomes a serious medical and social concern due to its high
      recurrence and mortality rates. Thus, it is urgent to search a novel prognostic
      biomarker and targeted therapy with high sensitivity and specificity. In this
      study, we used the human bladder cancer cell line EJ as an immunogen to generate
      a novel mouse monoclonal antibody KMP1 that specifically bound to bladder cancer,
      and then, the antitumor effect of KMP1 against bladder cancer was investigated
      both in vivo and in vitro. The results showed that expression of the KMP1 epitope
      is consistent with clinical severity and prognosis of bladder cancer.
      Furthermore, KMP1 not only significantly inhibited the proliferation, migration,
      and adhesion of EJ cells in vivo, but also suppressed the xenograft tumor growth
      in nude mice compared with the control group treated with mIgG. Subsequently, the
      underlying mechanism of KMP1 against bladder cancer was explored via antigen
      affinity chromatography and mass spectrometry. CD44 located on the cytomembrane
      was found as the antigen of KMP1. Using RNA interference technology to knock down
      CD44 expression, we further identified that KMP1 has the antitumor activity by
      binding to CD44 and blocking its functions. In conclusion, KMP1 might be valuable
      for development as a promising specific diagnostic biomarker or targeted agent
      for bladder cancer.

PMID- 29577647
TI  - Long noncoding RNA LINC00152 is a potential prognostic biomarker in patients with
      high-grade glioma.
AB  - AIMS: To investigate the role of LINC00152 in high-grade glioma (HGG). METHODS:
      We collected data from the Chinese Glioma Genome Atlas (CGGA) microarray, CGGA
      RNA sequencing, and GSE16011 datasets to evaluate the expression and prognostic
      relationship of LINC00152 in patients with HGGs. A knockdown assay was performed
      to determine the function of LINC00152 in glioma development and progression in
      vitro and in vivo. RESULTS: The expression of LINC00152 was increased with glioma
      grade, especially in the mesenchymal TCGA subtype. LINC00152 was independently
      associated with poor prognosis, and the overall survival (OS) of the high
      expression group was shorter than the low expression group (median OS 14.77 vs
      9.65 months; P = 0.0216) in the CGGA microarray dataset. The results were
      validated in the other 2 datasets. Based on the expression of LINC00152, 4288
      (2519 positively; 1769 negatively) probes were extracted to perform a biological
      process analysis using the Database for Annotation, Visualization, and Integrated
      Discovery. Positively regulated genes were enriched in immune response, apoptotic
      process, cell adhesion, and regulation of cell proliferation. The clinical and
      molecular features of HGG patients indicated that patients in the LINC00152 high
      expression group tended to display the mesenchymal type, older (>=46 years),
      isocitrate dehydrogenase1 wild-type, O(6)-methylguanine DNA methyltransferase
      unmethylated, nonchemotherapy, and low karnofsky performance status.
      Functionally, knockdown of LINC00152 inhibited cell proliferation, migration, and
      invasion and increased the sensitivity of chemotherapy in vitro. CONCLUSION: Our
      results indicate that knockdown of LINC00152 could inhibit tumor growth in vivo.
      LINC00152 could serve as a potential prognostic biomarker in patients with HGG.

PMID- 29577648
TI  - Safety and feasibility of laparoscopic gastrectomy accompanied by D1+ lymph node
      dissection for early gastric cancer in elderly patients.
AB  - INTRODUCTION: The age of patients with gastric cancer has increased worldwide.
      The aim of this study was to investigate the safety and feasibility of
      laparoscopic gastrectomy (LG) for early gastric cancer in elderly patients.
      METHODS: We retrospectively investigated 221 consecutive patients who underwent
      LG for early gastric cancer during a 5-year period (January 2010 to December
      2014). We divided the patients into two groups: elderly patients (>=75 years old)
      and younger patients (<75 years old). We compared these two groups with respect
      to clinical characteristics, histopathological findings, intraoperative factors,
      and postoperative outcomes. RESULTS: The preoperative characteristics were
      similar in both groups. Except for the number of harvested lymph nodes (42.0 vs
      34.9; P = 0.0016), the short-term operative outcomes, including postoperative
      complications and histopathological findings, were comparable between the two
      groups. Although significantly fewer lymph nodes were harvested in the elderly
      group, the overall survival and relapse-free survival rates did not significantly
      differ between the groups. Postoperative complications, such as acute
      cholecystitis and internal hernia, occurred during the long-term postoperative
      period after LG, and these unexpected complications were more frequently observed
      in elderly patients. All elderly patients required additional emergent surgeries
      for delayed complications. CONCLUSION: The outcomes of LG for early gastric
      cancer in elderly patients seem to be reasonable. Aggressive lymph node
      dissection may be omissible in elderly patients with acceptable results. LG can
      be a safe and feasible procedure in elderly patients. However, the higher rate of
      delayed but urgent complications during the long-term postoperative period must
      be considered.

PMID- 29577646
TI  - Performance of the UroVysion(r) FISH assay for the diagnosis of malignant
      effusions using two cutoff strategies.
AB  - The cytological examination of cavity fluids has limited sensitivity in the
      diagnosis of malignancy. Aneuploidy, which is commonly observed in neoplastic
      cells, could potentially be used as an ancillary diagnostic tool. To evaluate the
      detection of aneuploid cells in cavitary effusion samples using the fluorescence
      in situ hybridization (FISH) assay UroVysion(r) with some adaptations and two
      different cutoff strategies. Seventy samples of pleural or peritoneal fluid with
      positive (n = 40), negative (n = 15), or suspicious (n = 15) oncotic cytology
      were subjected to FISH assay with the multitarget UroVysion(r) kit, which is
      composed of probes that hybridize to the centromeric region of chromosomes 3, 7,
      and 17 and to the locus 9p21. FISH performance was evaluated using two different
      cutoffs: (1) the manufacturer's cutoff (M-FISH) and 2) a proposed cutoff (P
      FISH). Using M-FISH, the diagnostic sensitivity was 57.1%, specificity 87.5%, and
      accuracy 60.0%; with P-FISH, the sensitivity was 87.3%, specificity 71.4%, and
      accuracy 85.7%. When combined with cytology, the sensitivity, specificity, and
      accuracy were 88.0%, 83.3%, and 87.8%, respectively. Malignant cells presented a
      predominance of chromosomal gains. The UroVysion(r) test using the P-FISH cutoff
      was effective in demonstrating aneuploid cells in all malignant effusions,
      confirming the diagnosis of malignancy even in cases with suspicious cytology.

PMID- 29577650
TI  - Article alerts: Items from 2013.
AB  - This eighth installment of 'Article Alerts' includes a print component with 200
      methodological articles about research synthesis published in 2013. Since the
      preceding installment, more than 3400 articles, dissertations, book chapters, and
      other types of work in this methodological domain have been added to the archive
      component, all from 2009 to 2013. The online Supporting Information now includes
      over half of the parent compilation's more than 26 000 records: 1000 from the
      print component and more than 13 000 from the archive component. Current online
      addresses for similar bibliographic resources are provided.

PMID- 29577649
TI  - Exopolysaccharides from a Codonopsis pilosula endophyte activate macrophages and
      inhibit cancer cell proliferation and migration.
AB  - BACKGROUND: Exopolysaccharides with structural diversity have shown wide
      applications in biomaterial, food, and pharmaceutical industries. Herein, we
      isolated an endophytic strain, 14-DS-1, from the traditional medicinal plant
      Codonopsis pilosula to elucidate the characteristics and anti-cancer activities
      of purified exopolysaccharides. METHODS: HPLC and GC-MS were conducted to purify
      and characterize the exopolysaccharides isolated from 14-DS-1. Quantitative RT
      PCR, cell migration assays, immunofluorescence staining, and flow cytometry
      analysis were conducted to investighate the biological activity of DSPS. RESULTS:
      We demonstrated that exopolysaccharides isolated from 14-DS-1 (DSPS), which were
      predominately composed of six monosaccharides, showed anti-cancer activities.
      Biological activity analysis revealed that exposure to DSPS induced macrophage
      activation and polarization by promoting the production of TNF-alpha and nitric
      oxide. Further analysis revealed that DSPS treatment promoted macrophage
      infiltration, whereas cancer cell migration was suppressed. In addition, DSPS
      exposure led to S-phase arrest and apoptosis in cancer cells. Immunofluorescence
      staining revealed that treatment with DSPS resulted in defects in spindle
      orientation and positioning. CONCLUSION: These findings thus suggest that DSPS
      may have promising potential in cancer therapy.

PMID- 29577651
TI  - Prostate-specific antigen nadir within 12 months as an early surrogate marker of
      biochemical failure and distant metastasis after low-dose-rate brachytherapy or
      external beam radiotherapy for localized prostate cancer.
AB  - Prostate-specific antigen nadir (nPSA) after radiotherapy for localized prostate
      cancer has been investigated as a predictor. However, nPSA usually requires
      several years, limiting its clinical utility. We investigated the significance of
      nPSA within 12 months (nPSA12) after low-dose-rate prostate brachytherapy (LDR
      PB) or external beam radiotherapy (EBRT) on treatment outcomes. Between 2006 and
      2014, 663 patients with prostate cancer were treated with LDR-PB or EBRT at two
      institutions. Four hundred and seventy-four men received LDR-PB and 189 men
      received EBRT, without androgen deprivation therapy. The Kaplan-Meier method was
      used for biochemical failure (BF)-free survival (BFFS) and distant metastasis
      (DM)-free survival (DMFS) analyses, and multivariable Cox regression analysis was
      performed. The median follow-up was 61.3 months. The median nPSA12 in the LDR-PB
      and EBRT cohorts was 0.7 and 1.0 ng/mL, respectively. The 7-year BFFS and DMFS
      rates in LDR-PB patients with nPSA12 <= 0.7 ng/mL were 99.1% and 99.5%,
      respectively; when nPSA12 was >0.7 ng/mL, they were 90.2% and 94.8%,
      respectively. In EBRT patients with nPSA12 <= 1.0 ng/mL, BFFS and DMFS rates were
      85.4% and 98.5%, respectively; when nPSA12 was >1.0 ng/mL, they were 67.1% and
      87.2%, respectively. nPSA12 was an independent predictor of BF and DM in both
      cohorts (LDR-PB, P = 0.004 and 0.020, respectively; EBRT, P = 0.005 and 0.041,
      respectively). The nPSA12 after LDR-PB or EBRT is significantly associated with
      treatment outcomes of prostate cancer. Higher nPSA12 may identify patients at
      high risk of relapse who might benefit from salvage treatment.

PMID- 29577652
TI  - Preliminary study of the homologous recombination repair pathway in mouse
      spermatogonial stem cells.
AB  - The present study was designed to detect DNA repair response through the
      homologous recombination pathway in mouse spermatogonial stem cells. Mouse
      spermatogonial stem cells (mSSCs) were obtained from the adult DBA/2 mouse testes
      by MACS sorting. mSSCs and mice animals were divided into four groups (30 min, 2,
      24 h, control) and treated with ionizing irradiation while the control group
      received pseudo-irradiation. Proteins involved in the homologous recombination
      pathway (gammaH2AX, ATM, RAD51, CtIP, and RPA2) were assessed in mSSCs both in
      vitro and in vivo. Moreover, the non-homologous end-joining or homologous
      recombination (NHEJ/HR) reporter plasmids were transfected into mSSCs to assess
      NHEJ/HR pathway activity after DNA double-strand break (DSB). gammaH2AX, a
      classical DNA DSB marker, was absent in mSSCs both in vivo and in vitro after DSB
      repair, but was highly expressed in other tissue stem cells. In addition, ATM and
      phosphorylated ATM (p-ATM) were involved in DNA damage response (DDR) in mSSCs. p
      ATM foci were overexpressed immediately after irradiation (30 min and 2 h), but
      gradually decreased over the repair time. The HR pathway-related proteins, CtIP
      and RPA2 were negatively regulated after treatment in Western blot (WB). NHEJ/HR
      reporter plasmid transfection indicated that the HR pathway played a minor role
      in mSSCs during DDR, consistent with the WB findings. This study demonstrates
      that mSSCs may have a unique response to DNA damage since crucial proteins
      involved in HR pathway were negatively regulated after DSB. In addition, the
      expression level of p-ATM, but not gammaH2AX, was increased after DSB, suggesting
      that DNA damage repair in mSSCs might be a gammaH2AX-independent response.
      Furthermore, the HR pathway may play a minor role during DDR in mSSCs.

PMID- 29577653
TI  - Cobalt Complex with Redox-Active Imino Bipyridyl Ligand for Electrocatalytic
      Reduction of Carbon Dioxide to Formate.
AB  - An imino bipyridine cobalt(II) complex was developed for the electrocatalytic
      reduction of CO2 to formate in acetonitrile with a faradaic efficiency of
      approximately 80 %. For comparison, a symmetric bis-imino pyridine complex showed
      lower catalytic activity because of less conjugation in the system. Cyclic
      voltammetry, electron paramagnetic resonance and IR spectroscopy studies provided
      mechanistic details and the structures of the key intermediates. DFT calculations
      confirmed the role of large pi-conjugated groups for stabilizing key
      intermediates through electronic conjugation.

PMID- 29577656
TI  - Detecting the effect of bisphosphonates during osteoporosis treatment on jawbones
      using multidetector computed tomography: The OSTEOSYR project.
AB  - AIM: The aim of the present cross-sectional study was to investigate the effects
      of bisphosphonates (BP), prescribed for osteoporosis, on jawbones using
      multidetector computed tomography (MDCT). METHODS: Fifty-three women who had dual
      energy X-ray absorptiometry examination were scanned by MDCT. Both the cortical
      and the trabecular parts of the alveolar and the cortical bones were compared
      between BP users and non-BP users using a number of radiological measurements.
      Linear regression was used for the statistical analysis. RESULTS: The cortical
      part of the basal bone of the mandible revealed a significant increase in the BP
      group (.001 > P-value <= .026) after using BP for 5 years. No alternations were
      observed in the trabecular part of the basal bone or in the cortical or
      trabecular parts of the alveolar bone over the same duration. CONCLUSIONS: The
      use of BP as a treatment for osteoporosis for 5 years increased the thickness of
      the cortex of the basal bone of the mandible, as detected by MDCT. The other
      parts of the jawbones showed no influence by BP for such a purpose, as detected
      on MDCT images. Accordingly, models (equations) for predicting the alternations
      in the inferior cortex of the mandible induced by BP therapy during osteoporosis
      have been suggested.

PMID- 29577654
TI  - Flea market finds and global exports: Four multistate outbreaks of human
      Salmonella infections linked to small turtles, United States-2015.
AB  - Zoonotic transmission of Salmonella infections causes an estimated 11% of
      salmonellosis annually in the United States. This report describes the
      epidemiologic, traceback and laboratory investigations conducted in the United
      States as part of four multistate outbreaks of Salmonella infections linked to
      small turtles. Salmonella isolates indistinguishable from the outbreak strains
      were isolated from a total of 143 ill people in the United States, pet turtles,
      and pond water samples collected from turtle farm A, as well as ill people from
      Chile and Luxembourg. Almost half (45%) of infections occurred in children aged
      <5 years, underscoring the importance of the Centers for Disease Control and
      Prevention recommendation to keep pet turtles and other reptiles out of homes and
      childcare settings with young children. Although only 43% of the ill people who
      reported turtle exposure provided purchase information, most small turtles were
      purchased from flea markets or street vendors, which made it difficult to locate
      the vendor, trace the turtles to a farm of origin, provide education and enforce
      the United States federal ban on the sale and distribution of small turtles.
      These outbreaks highlight the importance of improving public awareness and
      education about the risk of Salmonella from small turtles not only in the United
      States but also worldwide.

PMID- 29577655
TI  - First insights into Puumala orthohantavirus circulation in a rodent population in
      Alsace, France.
AB  - In-depth knowledge on the mechanisms that maintain infection by a zoonotic
      pathogen in an animal reservoir is the key to predicting and preventing
      transmission to humans. The Puumala orthohantavirus (PUUV), the most prevalent
      orthohantavirus in Western Europe, causes a mild form of haemorrhagic fever with
      renal syndrome (HFRS) in humans. In France, this endemic illness affects the
      north-eastern part of the country. We conducted a 4-year capture-mark-recapture
      study in a bank vole population, combined with molecular analyses, to explore the
      epidemiological situation of PUUV in Alsace, a French region where human cases
      have occurred, but for which no studies have been conducted on this reservoir
      host. PUUV-infected bank voles were detected in the 2 years that showed high bank
      vole density with a prevalence of 4%. The individual PUUV sequences identified in
      this study were similar from year to year and similar to other French sequences.
      On a very small spatial scale, the distribution of seropositive bank voles was
      very heterogeneous in time and space. The short distances travelled on average by
      bank voles resulted in spatial clusters of seropositive rodents, which spread
      only very gradually throughout the year.

PMID- 29577657
TI  - Fast uncertainty quantification of activation sequences in patient-specific
      cardiac electrophysiology meeting clinical time constraints.
AB  - We present a fast, patient-specific methodology for uncertainty quantification in
      electrophysiology, aimed at meeting the time constraints of clinical
      practitioners. We focus on computing the statistics of the activation map, given
      the uncertainties associated with the conductivity tensor modeling the fiber
      orientation in the heart. We use a fast parallel solution method implemented on a
      graphics processing unit for the eikonal approximation, in order to compute the
      activation map and to sample the random fiber field with correlation on the basis
      of geodesic distances. While this enables to perform uncertainty quantification
      studies with a manageable computational effort, the required time frame still
      exceeds clinically suitable time expectations. In order to reduce it further by 2
      orders of magnitude, we rely on Bayesian multifidelity methods. In particular, we
      propose a low-fidelity model that is patient-specific and free from the
      additional training cost associated with reduced models. This is achieved by a
      sound physics-based simplification of the full eikonal model. The low-fidelity
      output is then corrected by the standard multifidelity framework. In practice,
      the complete procedure only requires approximately 100 new runs of our eikonal
      graphics processing unit solver for producing the sought estimates and their
      associated credible intervals, enabling a full online analysis in less than 5
      minutes.

PMID- 29577658
TI  - Metabolism study for CUMYL-4CN-BINACA in human hepatocytes and authentic urine
      specimens: Free cyanide is formed during the main metabolic pathway.
AB  - To further elucidate the metabolism of CUMYL-4CN-BINACA, a new synthetic
      cannabinoid with a cyano group, and to evaluate biomarkers, we incubated the
      substance in human hepatocytes and analysed 9 authentic urine specimens. We also
      quantified CUMYL-4CN-BINACA and cyanide in blood and provide comprehensive data
      on the 7 autopsy cases, 5 of them determined CUMYL-4CN-BINACA intoxications. For
      metabolite elucidation, CUMYL-4CN-BINACA was incubated with pooled human
      hepatocytes for up to 5 hours, urine samples were analysed with and without
      enzymatic hydrolysis. Data was acquired in data-dependent mode by ultra-high
      performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)
      with an Agilent 6550 QTOF. For quantitative analysis of CUMYL-4CN-BINACA, blood
      samples were precipitated and analysed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Cyanide was determined by gas chromatography-headspace
      nitrogen phosphorus detection (GC-headspace-NPD). CUMYL-4CN-BINACA was
      metabolised via CYP450-mediated hydroxylation at 4-butyl position generating a
      cyanohydrin (M12), which releases free cyanide to form an aldehyde intermediate
      and eventually generates 4-hydroxybutyl CUMYL-BINACA (M11) and CUMYL-BINACA
      butanoic acid (M10). Other minor metabolites were produced by hydroxylation,
      dihydroxylation, N-dealkylation, and dihydrodiol formation; glucuronidation was
      observed. One urine sample showed high intensities of M10 and a wide variety of
      metabolites; the other samples contained fewer metabolites in low abundance and 1
      sample showed no metabolites. CUMYL-4CN-BINACA blood concentrations ranged from
      0.1 to 8.3 ng/g showing an overlap between fatal and non-fatal concentrations.
      One blood sample contained 0.36 MUg/g cyanide. Release of free cyanide during
      metabolism is worrying as it might induce liver toxicity. As suggested earlier,
      CUMYL-BINACA butanoic acid is the most abundant biomarker in urine, but
      monitoring of additional metabolites or, even better, analysis for the parent in
      blood is recommended.

PMID- 29577659
TI  - Trajectories of change in symptom distress in a clinical group of late
      adolescents: The role of maladaptive personality traits and relations with
      parents.
AB  - In this study, it was analysed whether trajectories of change in symptom distress
      could be identified in a clinical group of late adolescents with personality
      pathology. Furthermore, it was examined whether maladaptive personality traits
      and relations with parents were predictive of following one of these
      trajectories. Three latent classes emerged from growth mixture modelling with a
      symptom inventory (n = 911): a Stable High, a Strong Decreasing and a Moderate
      Decreasing trajectory. Subsequently, by using multinomial logistic regression
      analyses in a subsample of late-adolescents (n = 127), it was revealed that high
      levels of Negative Affectivity and Detachment were predictive of following the
      Strong Decreasing, and high levels of Detachment were predictive of following the
      Stable High trajectory. Support from or Negative Interactions with parents were
      not predictive of any of the trajectories. The current results contribute to the
      notion of individual trajectories of change in symptom distress and provide
      suggestions for screening patients on personality traits to gain insight in the
      course of this change. (c) 2018 The Authors Personality and Mental Health
      Published by John Wiley & Sons Ltd.

PMID- 29577660
TI  - ERAP1 molecular characterization: Identification of a de novo allelic variant.
AB  - The novel ERAP1 allelic variant is a missense polymorphism leading to the
      Arg53Pro substitution.

PMID- 29577661
TI  - Cross-sectional study to estimate the prevalence of enterohaemorrhagic
      Escherichia coli on hides of market beef cows at harvest.
AB  - Cattle hides are an important source of enterohaemorrhagic Escherichia coli
      (EHEC) carcass contamination at slaughter. Seven EHEC serogroups are adulterants
      in raw, non-intact beef: EHEC O26, O45, O103, O111, O121, O145 and O157. The
      objective of this study was to estimate the probability for hide contamination
      with EHEC among US market beef cows at slaughter and to test the effects of
      season and geographic region on prevalence of hide contamination. Hides (n = 800)
      of market cows were swabbed at slaughter immediately after exsanguination, prior
      to hide removal. Cows were sampled from two geographically distinct beef packing
      plants during four seasons of 2015. Cattle source was categorized by northern or
      southern region. Samples were tested for EHEC by a molecular screening assay. The
      effects of region, season and their interaction on the probability of hide
      contamination by each EHEC serogroup were tested in separate multilevel
      multivariable logistic regression models, accounting for the random effect of
      clustering by plant. Statistical significance was set alpha = .05. Of 800 total
      samples, at least one EHEC was detected on 630 (79%) hides. Enterohaemorrhagic E.
      coli O26 was detected on 129 (16%) of all hides sampled, EHEC O45 on 437 (55%),
      EHEC O103 on 289 (36%), EHEC O111 on 189 (24%), EHEC O121 on 140 (18%), EHEC O145
      on 171 (21%) and EHEC O157 on 89 (11%). Detection of EHEC O26 and EHEC O121 was
      associated with season. Season and region were associated with detecting EHEC O45
      and EHEC O157. Season-by-region interactions were associated with the outcome of
      detecting EHEC O103, EHEC O111 and EHEC O145. Season, region of origin and the
      interaction of these factors affect hide contamination of market beef cattle at
      slaughter by EHEC, and each serogroup responds to these factors uniquely.

PMID- 29577662
TI  - Enhancing Zeolite Performance by Catalyst Shaping in a Mesoscale Continuous-Flow
      Diels-Alder Process.
AB  - In contrast to most lab-scale batch procedures, a continuous-flow implementation
      requires a thorough consideration of the solid catalyst design. In a previous
      study, irregular zeolite pellets were applied in a miniaturized continuous-flow
      reactor for the Diels-Alder reaction in the construction of norbornene scaffolds.
      After having faced the challenges of continuous operation, the aim of this study
      is to exploit catalyst structuring. To this end, microspheres with high
      uniformity and various sphere diameters were synthesized according to the
      vibrational droplet coagulation method. The influence of the use of these novel
      zeolite shapes in a mesoscale continuous-flow Diels-Alder process of
      cyclopentadiene and methyl acrylate is discussed. An impressive enhancement of
      catalyst lifetime is demonstrated, as even after a doubled process time of 14 h,
      the microspheres still exceeded the conversion after 7 h when using zeolite
      pellets by 30 %. A dual reason is found for this beneficial impact of catalyst
      shaping. The significant improvement in catalyst longevity can be attributed to
      the interplay of the chemical composition and the porosity structure of the
      microspheres.

PMID- 29577663
TI  - Inhibition of breast cancer cell growth by methyl pyropheophenylchlorin
      photodynamic therapy is mediated though endoplasmic reticulum stress-induced
      autophagy in vitro and vivo.
AB  - Autophagy and ER stress participated in the inhibition of MPPa-PDT on tumor
      growth, but the molecular links between them remain undefined. We just explore
      the molecular mechanism between them in vitro and vivo. CCK-8 assay and flow
      cytometer were used to detect the cytotoxicity and mode of cell death after MPPa
      PDT. Furthermore, the role of autophagy was verified in MPPa-PDT. Confocal
      microscopy was used to show the intracellular distribution of MPPa. ER stress
      markers and PERK signaling pathway were detected by western blot. While in vivo,
      tumor histology and immunohistochemistry were performed to show the effect of
      MPPa-PDT in mice. After MPPa-PDT, cells viability decreased in dose-dependent
      manner. Besides, the cell apoptosis increased along with the increasing of Beclin
      1and LC3B II but declining of P62. When pretreated with 3-MA, LC3B II formation
      and the cytotoxicity declined. MPPa-PDT caused increasing of ER stress markers
      (GRP78, CHOP) as MPPa accumulated in ER. However, pretreatment with ER stress
      inhibitor 4PBA, the expression of GRP78 and LC3B II was blocked but the PERK
      signaling pathway activated and the expression of P62 increased. In vivo, the
      tumor growth was significantly inhibited by MPPa-PDT. Besides, the appearance of
      ER stress and autophagy was further demonstrated by immunohistochemistry. Our
      findings demonstrate that autophagy mediated by MPPa-PDT was regulated by ER
      stress, via PERK signaling pathway, to kill MDA-MB-231 cells in vitro and vivo.

PMID- 29577664
TI  - Risk of thyroid cancer in relation to height, weight, and body mass index in
      Japanese individuals: a population-based cohort study.
AB  - Greater height and body mass index (BMI) have been associated with an increased
      risk of thyroid cancer incidence in Western countries. However, few
      epidemiological studies have assessed the association between anthropometric
      factors, such as BMI, height, or weight, and thyroid cancer incidence in Asian
      populations. Using the population-based Japan Public Health Center-based
      prospective study database, we investigated the relationship between
      anthropometric factors and thyroid cancer incidence. Data on anthropometric
      factors were collected through a self-administered questionnaire at baseline. The
      hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the
      Cox proportional hazards model, and the exposure level was categorized into
      quintiles. A total of 49,062 men and 53,661 women enrolled between 1990 and 1994
      were included in our analyses, and 191 cases (37 in men and 154 in women) of
      thyroid cancer were identified, with 1,695,702 person-years of follow-up until
      2010. Compared with the male group with height <=160 cm, HRs of the male groups
      with height 165-168 cm and >=169 cm were 3.92 (95% CI; 1.33-11.55, P = 0.013) and
      4.24 (95% CI; 1.32-13.61, P = 0.015), respectively, and the HR per 5-cm increase
      in height was 1.12 (95% CI 1.06-1.18, P < 0.001). In contrast, the association
      between anthropometric features and the risk of thyroid cancer did not
      significantly differ among women. In this population, an increase in risk for
      increased height was observed in men, but no associations between anthropometric
      indexes and thyroid cancer risk were observed in women.

PMID- 29577665
TI  - Relevance of Local Flexibility Near the Active Site for Enzymatic Catalysis:
      Biochemical Characterization and Engineering of Cellulase Cel5A From Bacillus
      agaradherans.
AB  - Detailed molecular mechanisms underpinning enzymatic reactions are still a
      central problem in biochemistry. The need for active site flexibility to sustain
      catalytic activity constitutes a notion of wide acceptance, although its direct
      influence remains to be fully understood. With the aim of studying the
      relationship between structural dynamics and enzyme catalysis, the cellulase
      Cel5A from Bacillus agaradherans is used as a model for in silico comparative
      analysis with mesophilic and psychrophilic counterparts. Structural features that
      determine flexibility are related to kinetic and thermodynamic parameters of
      catalysis. As a result, three specific positions in the vicinity of the active
      site of Cel5A are selected for protein engineering via site-directed mutagenesis.
      Three Cel5A variants are generated, N141L, A137Y and I102A/A137Y, showing a
      concomitant increase in the catalytic activity at low temperatures and a decrease
      in activation energy and activation enthalpy, similar to cold-active enzymes.
      These results are interpreted in structural terms by molecular dynamics
      simulations, showing that disrupting a hydrogen bond network in the vicinity of
      the active site increases local flexibility. These results provide a structural
      framework for explaining the changes in thermodynamic parameters observed between
      homologous enzymes with varying temperature adaptations.

PMID- 29577666
TI  - Atmospheric Plasma Deposition of Methacrylate Layers Containing Catechol/Quinone
      Groups: An Alternative to Polydopamine Bioconjugation for Biomedical
      Applications.
AB  - Bioconjugation of enzymes on coatings based on polydopamine (PDA) layers is an
      appealing approach to control biological responses on biomedical implant
      surfaces. As alternative to PDA wet deposition, a fast, solvent-free, and dynamic
      deposition approach based on atmospheric-pressure plasma dielectric barrier
      discharge process is considered to deposit on metallic surfaces acrylic-based
      interlayers containing highly chemically reactive catechol/quinone groups. A
      biomimetic approach based on covalent immobilization of Dispersin B, an enzyme
      with antibiofilm properties, shows the bioconjugation potential of the novel
      plasma polymer layers. The excellent antibiofilm activity against Staphylococcus
      epidermidis is comparable to the PDA-based layers prepared by wet chemical
      methods with slow deposition rates. A study of preosteoblastic MG-63 human cell
      line viability and adhesion properties on plasma polymer layers demonstrates
      early interaction required for biomedical applications.

PMID- 29577667
TI  - Increasing the Photoautotrophic Growth Rate of Synechocystis sp. PCC 6803 by
      Identifying the Limitations of Its Cultivation.
AB  - Many conditions have to be optimized in order to be able to grow the
      cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis) for an extended period
      of time under physiologically well-defined and constant conditions. It is still
      poorly understood what limits growth of this organism in batch and continuous
      cultures in BG-11, the standard medium used to grow Synechocystis. Through a
      series of batch experiments in flasks and continuous mode experiments in advanced
      photobioreactors, it is shown that the limiting nutrient during batch cultivation
      is sulfate, the depletion of which leads to ROS formation and rapid bleaching of
      pigments after entry into stationary phase. In continuous mode, however, the
      limiting nutrient is iron. Optimizing these growth conditions resulted in a so
      far highest growth rate of 0.16 h-1 (4.3 h doubling time), which is significantly
      higher than the textbook value of 0.09 h-1 (8 h doubling time). An improved
      medium, BG-11 for prolonged cultivation (BG-11-PC) is introduced, that allows for
      controlled, extended cultivation of Synechocystis, under well-defined
      physiological conditions. The data present here have implications for mass
      culturing of cyanobacteria.

PMID- 29577668
TI  - Most commensally bacterial strains in human milk of healthy mothers display
      multiple antibiotic resistance.
AB  - Recent reports have shown that food-borne or commensal bacteria can function as
      reservoirs of antibiotic resistance. However, the antibiotic susceptibility of
      bacterial isolates of most milk samples or the total bacterial counts (TBC) in
      human milk from healthy donors, are not fully understood in Taiwan. Thus, five
      healthy mothers were randomly recruited each month, and totally 30 mothers
      without any symptoms of infection were recruited over 6 months. Milk samples were
      then harvested and analyzed immediately after collection. The antibiotic
      susceptibility was analyzed in bacteria isolated from milk samples using nine
      clinically relevant antibiotics, such as oxacillin, ampicillin, cephalothin,
      amoxicillin, ciprofloxacin, erythromycin, clindamycin, gentamicin, and
      oxytetracycline. The Staphylococcus strains (48 isolates) found in milk resisted
      to 48.6 +/- 20.1% selected antibiotics. Streptococcus-related isolates (8
      isolates) exhibited resistance to 41.7 +/- 26.4% selected antibiotics.
      Acinetobacter isolates (5 isolates) were resistant to 66.7 +/- 13.6% antibiotics,
      and Enterococcus isolates (5 isolates) were resistant to 73.3 +/- 6.1% tested
      antibiotics. Rothia-related isolates (4 isolates) were resisted to 58.2 +/- 31.9%
      of tested antibiotics. In contrast, Corynebacterium isolates (5 isolates) were
      sensitive to 66%-100% of selected antibiotics. Furthermore, the TBC ranged from
      40 to 710,000 CFU/ml, implying a wide spectrum of bacteria in milk from healthy
      mothers. Despite this, all milk donors were healthy during sampling, and they did
      not show any symptoms related to mastitis or subclinical mastitis. According to
      the previously described TBC criteria for the use of donated human milk, only 73%
      of the current milk samples could be accepted for the milk bank. In conclusion,
      the majority of the isolated bacterial strains from current human milk samples
      are multiresistant strains. In milk samples for preterm infants or milk banks,
      higher TBC levels or potentially antibiotic-resistant bacteria in some milk
      samples have supported people using approaches to disinfect human milk partially.

PMID- 29577669
TI  - Protista: An annotated selection of World Wide Web sites relevant to the topics
      in environmental microbiology.

PMID- 29577670
TI  - An autotrophic H2 -oxidizing, nitrate-respiring, Tc(VII)-reducing Acidovorax sp.
      isolated from a subsurface oxic-anoxic transition zone.

PMID- 29577671
TI  - Prognostic significance of NFIA and NFIB in esophageal squamous carcinoma and
      esophagogastric junction adenocarcinoma.
AB  - The nuclear factor I (NFI) family members, especially NFIA and NFIB, play
      essential roles in cancers. The roles of NFIA and NFIB in esophageal squamous
      cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA) remain
      poorly known. This study aimed to determine the expression of NFIA and NFIB in
      ESCC and EJA and elucidate their prognostic significance. The expression of NFIA
      and NFIB was examined in 163 ESCC samples and 26 EJA samples by
      immunohistochemistry. The results showed that high NFIA expression correlated
      significantly with poor differentiation, lymph node metastasis, and advanced TNM
      stage in patients with ESCC. High NFIB expression only correlated with poor
      differentiation in patients with ESCC. Survival analysis showed that NFIA but not
      NFIB associated with short overall survival (OS) and disease-free survival (DFS)
      of patients with ESCC. On the other hand, high NFIB expression correlated with
      lymph node metastasis, advanced TNM stage, and short OS and DFS in patients with
      EJA. Finally, multivariate analysis demonstrated that high NFIA expression was an
      independent prognostic factor for ESCC. Taken together, these results
      demonstrated that NFIA and NFIB could serve as prognostic indicators for ESCC and
      EJA, respectively.

PMID- 29577672
TI  - Cancer risk in patients with alopecia areata: a nationwide population-based
      matched cohort study.
AB  - Alopecia areata (AA) is an organ-specific autoimmune disorder. Defective immune
      system related disorders are prone to increase the risk of cancer formation.
      However, the association among AA and variety of cancer types had never been
      studied. A nationwide population-based matched cohort study was conducted to
      evaluate the cancer risk in patients with AA. Records from Taiwan National Health
      Insurance Research Database were analyzed. Cases of AA from 1997 to 2013 and
      cancers registered in the catastrophic illness profile from the same time period
      were collected. The standard incidence ratio (SIR) of each cancer was calculated.
      In total, 2099 cancers among 162,499 patients with AA and without prior cancers
      were identified. The overall cancer risks in AA patients were slightly decreased,
      especially among male subjects (SIR: 0.89). Refer to individual cancer, the
      cancer risk of nonmelanoma skin cancer (NMSC) (SIR: 0.59), upper GI cancer (SIR:
      0.70), liver cancer (SIR: 0.82), uterine, and cervix cancer (SIR: 0.84) were
      significantly lower in patients with AA. In contrast, AA patients were inclined
      to have lymphoma, breast cancer, kidney, and urinary bladder cancer with the SIR
      of 1.55, 2.93, and 2.95, respectively. Age stratified analyses revealed female AA
      patients younger than 50 years old have even higher risk of breast cancer (SIR:
      3.37). Further sensitivity analysis showed similar results after excluding major
      autoimmune disorders. Cancer risk in AA patients is organ specific, and it is not
      associated with the underlying autoimmune disorders in patients with AA.

PMID- 29577673
TI  - Coping with arsenic stress: Adaptations of arsenite-oxidizing bacterial membrane
      lipids to increasing arsenic levels.
AB  - Elevated levels of arsenic (As) in aquifers of South East Asia have caused
      diverse health problems affecting millions of people who drink As-rich
      groundwater and consume various contaminated agriculture products. The
      biogeochemical cycling and mobilization/immobilization of As from its mineral
      bound phase is controlled by pH, oxic/anoxic conditions, and different microbial
      processes. The increased As flux generated from ongoing biogeochemical processes
      in the subsurface in turn affects the in situ microbial communities. This study
      analyzes how the indigenous arsenite-oxidizing bacteria combat As stress by
      various biophysical alterations and self-adaptation mechanisms. Fifteen arsenite
      oxidizing bacterial strains were isolated and identified using a polyphasic
      approach. The bacterial strains isolated from these aquifers belong predominantly
      to arsenite-oxidizing bacterial groups. Of these, the membrane-bound phospholipid
      fatty acids (PLFA) were characterized in seven selected bacterial isolates grown
      at different concentrations of As(III) in the medium. One of the significant
      findings of this study is how the increase in external stress can induce
      alteration of membrane PLFAs. The change in fatty acid saturation and alteration
      of their steric conformation suggests alteration of membrane fluidity due to
      change in As-related stress. However, different bacterial groups can have
      different degrees of alteration that can affect sustainability in As-rich
      aquifers of the Bengal Delta Plain.

PMID- 29577675
TI  - Identification of the novel KIR2DL4*00106 allele in a southern Chinese Han
      individual.
AB  - The novel 2DL4*00106 allele differs from the closest allele 2DL4*00102 by a
      silent mutation.

PMID- 29577674
TI  - A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome
      positive chronic myeloid leukemia in chronic phase: ENESTKorea.
AB  - Although nilotinib has improved efficacy compared to imatinib, suboptimal
      response and intolerable adverse events (AEs) limit its effectiveness in many
      patients with chronic myeloid leukemia in chronic phase (CML-CP). We investigated
      the 2-year efficacy and safety of nilotinib and their relationships with plasma
      nilotinib concentrations (PNCs). In this open-label, multi-institutional phase 4
      study, 110 Philadelphia chromosome-positive CML-CP patients were treated with
      nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and
      AEs were monitored for up to 24 months. The 24-month cumulative MR4.5 rate was
      evaluated as the primary endpoint. Plasma samples were collected from 94 patients
      to determine PNCs, and the per-patient mean was used to categorize them into four
      mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between
      groups. With a median follow-up of 22.2 months, the 24-month cumulative MR4.5
      rate was 56.2% (95% confidence interval, 44.0%-8.3%), and the median time to
      MR4.5 was 23.3 months. There were no significant differences in the cumulative
      rates of major molecular response, MR4 , and MR4.5 between MPNC groups. One
      patient died due to acute viral hepatitis, and two developed hematological or
      cytogenetic relapse, while no progression to accelerated or blast phase was
      observed. Safety results were consistent with previous studies with no new safety
      signal identified. Across the MPNC groups, there was no significant linear trend
      in the frequency of AEs. Nilotinib is highly effective for the treatment of CML
      CP with manageable AEs. The measurement of PNC has no predictive value for
      patient outcomes and is thus not found to be clinically useful. This study is
      registered with clinicaltrials.gov, Number NCT03332511.

PMID- 29577676
TI  - Superficial radiotherapy as a treatment alternative for recurrent conjunctival
      squamous cell carcinoma: a case study.
AB  - This case study discusses the use of superficial radiotherapy (SXRT) in the
      treatment of recurrent conjunctival squamous cell carcinoma (SCC). Conjunctival
      SCC is often an aggressive cancer, with surgery the current standard of care.
      There is currently limited literature on alternative treatment options to treat
      conjunctival SCC recurrences that enable ocular function preservation.
      Furthermore, the use of SXRT in this setting is not well-reported. Technical
      feasibility, practical limitations and potential side effects of SXRT (in
      comparison to other treatment options) are discussed in this case study. This
      case describes a 62 years old male with limited treatment options following
      multiple recurrences of conjunctival SCC. He was prescribed a therapeutic SXRT
      dose of 48.4 Gy in 22 fractions (5 fractions/week). At 6-month follow-up, there
      was no evidence of residual or recurrent disease, or any significant objective or
      patient reported treatment induced side effects. This case study provides
      preliminary evidence for the potential application of SXRT for conjunctival SCC.
      The benefits reported in this case study warrant further investigation of the
      applicability of SXRT in a larger patient cohort, with the potential to provide
      patients with a less invasive treatment alternative for recurrent conjunctival
      SCC.

PMID- 29577677
TI  - Phase determination using chromosomal microarray and fluorescence in situ
      hybridization in a patient with early onset Parkinson disease and two deletions
      in PRKN.
AB  - BACKGROUND: Mutations in the parkin gene (PRKN) are the most commonly identified
      genetic factors in early onset Parkinson disease (EOPD), with biallelic
      mutations, resulting in a clinical phenotype. However, normal variation is also
      common in PRKN, particularly in the form of copy number variation (CNV),
      challenging interpretation of genetic testing results. Here we report a case of a
      29-year-old male with EOPD and two deletions in PRKN detected by chromosomal
      microarray (CMA). METHODS: The proband was clinically examined by a neurologist
      for postural instability with frequent falls, bradykinesia, gait freezing with
      festination, and hypophonia. Chromosomal microarray analysis (CMA) was performed
      on the proband and his parents using the Affymetrix CytoScan HD microarray.
      Subsequent fluorescence in situ hybridization (FISH) was performed on the proband
      and both parents. RESULTS: Chromosomal microarray detected the presence of two
      deletions of PRKN in the proband. Parental CMA analysis was performed to
      determine the clinical significance of this finding, as well as to demonstrate
      phase of these deletions. Parental CMA revealed that one deletion was paternally
      inherited and one deletion was de novo. A custom FISH approach was then
      successfully used to phase the deletions. CONCLUSION: Chromosomal microarray and
      fluorescence in situ hybridization analysis of this trio identified two deletions
      in PRKN occurring in trans, providing a genetic etiology for the clinical
      diagnosis of EOPD. The determination of inheritance and phase of the deletions
      was critical to the proper interpretation of these results. These findings
      highlight the utility of CMA in the detection of clinically relevant CNVs in
      cases of EOPD, and also serve to emphasize the importance of follow-up FISH and
      parental testing.

PMID- 29577678
TI  - Integrin Clustering Matters: A Review of Biomaterials Functionalized with
      Multivalent Integrin-Binding Ligands to Improve Cell Adhesion, Migration,
      Differentiation, Angiogenesis, and Biomedical Device Integration.
AB  - Material systems that exhibit tailored interactions with cells are a cornerstone
      of biomaterial and tissue engineering technologies. One method of achieving these
      tailored interactions is to biofunctionalize materials with peptide ligands that
      bind integrin receptors present on the cell surface. However, cell biology
      research has illustrated that both integrin binding and integrin clustering are
      required to achieve a full adhesion response. This biophysical knowledge has
      motivated researchers to develop material systems biofunctionalized with
      nanoscale clusters of ligands that promote both integrin occupancy and clustering
      of the receptors. These materials have improved a wide variety of biological
      interactions in vitro including cell adhesion, proliferation, migration speed,
      gene expression, and stem cell differentiation; and improved in vivo outcomes
      including increased angiogenesis, tissue healing, and biomedical device
      integration. This review first introduces the techniques that enable the
      fabrication of these nanopatterned materials, describes the improved biological
      effects that have been achieved, and lastly discusses the current limitations of
      the technology and where future advances may occur. Although this technology is
      still in its nascency, it will undoubtedly play an important role in the future
      development of biomaterials and tissue engineering scaffolds for both in vitro
      and in vivo applications.

PMID- 29577679
TI  - Removal and biodegradation of different petroleum hydrocarbons using the
      filamentous fungus Aspergillus sp. RFC-1.
AB  - Petroleum pollution inevitably occurs at any stage of oil production and exerts a
      negative impact on the environment. Some microorganisms can degrade petroleum
      hydrocarbons (PHs). Polluted sludge of Rumaila oil field was use to isolate the
      highly efficient hydrocarbon-degrading fungal strain. Aspergillus sp. RFC-1 was
      obtained and its degradation ability for petroleum hydrocarbons was evaluated
      through surface adsorption, cell uptake, hydrophobicity, surface tension,
      biosurfactant production, and emulsification activity. In addition, the
      degradation mechanism was investigated. The results indicated the strain RFC-1
      showed high removal activity for PHs, including biodegradation, adsorption, and
      emulsifiability. On the day 7 of incubation, the removal efficiencies of crude
      oil, naphthalene (NAP), phenanthrene (PHE), and pyrene (PYR) reached 60.3%,
      97.4%, 84.9%, and 90.7%, respectively. Biodegradation efficiencies of crude oil,
      NAP, PHE, and PYR were 51.8%, 84.6%, 50.3%, and 55.1%, respectively. Surface
      adsorption and cell absorption by live mycelial pellets followed a decreasing
      order: PYR >= PHE > NAP > crude oil. Adsorption by heat-killed mycelial pellets
      increased within 40 and 10 min for crude oil and PAHs, respectively, and remained
      constant thereafter. Effects of cell surface hydrophobicity, surface tension, and
      emulsification index were discussed. Intra- and extracellular enzymes of strain
      RFC-1 played important roles in PHs degradation. The strain RFC-1 is a
      prospective strain for removing PHs from aqueous environments.

PMID- 29577680
TI  - Streptococcus dysgalactiae subsp. dysgalactiae isolated from milk of the bovine
      udder as emerging pathogens: In vitro and in vivo infection of human cells and
      zebrafish as biological models.
AB  - Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is a major cause of bovine
      mastitis and has been regarded as an animal-restricted pathogen, although rare
      infections have been described in humans. Previous studies revealed the presence
      of virulence genes encoded by phages of the human pathogen Group A Streptococcus
      pyogenes (GAS) in SDSD isolated from the milk of bovine udder with mastitis. The
      isolates SDSD VSD5 and VSD13 could adhere and internalize human primary
      keratinocyte cells, suggesting a possible human infection potential of bovine
      isolates. In this work, the in vitro and in vivo potential of SDSD to
      internalize/adhere human cells of the respiratory track and zebrafish as
      biological models was evaluated. Our results showed that, in vitro, bovine SDSD
      strains could interact and internalize human respiratory cell lines and that this
      internalization was dependent on an active transport mechanism and that, in vivo,
      SDSD are able to cause invasive infections producing zebrafish morbidity and
      mortality. The infectious potential of these isolates showed to be isolate
      specific and appeared to be independent of the presence or absence of GAS phage
      encoded virulence genes. Although the infection ability of the bovine SDSD
      strains was not as strong as the human pathogenic S. pyogenes in the zebrafish
      model, results suggested that these SDSD isolates are able to interact with human
      cells and infect zebrafish, a vertebrate infectious model, emerging as pathogens
      with zoonotic capability.

PMID- 29577681
TI  - Determination of a radotinib dosage regimen based on dose-response relationships
      for the treatment of newly diagnosed patients with chronic myeloid leukemia.
AB  - Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for
      the treatment of chronic myeloid leukemia in chronic phase (CP-CML). Here, using
      the data from a Phase 3 study conducted in patients with newly diagnosed CP-CML,
      the dose-efficacy as well as dose-safety relationship analyses were performed to
      determine a safe and effective initial dosage regimen of radotinib. A significant
      positive association was detected between the starting dose of radotinib adjusted
      for body weight (Dose/BW) and the probability of dose-limiting toxicity (>=grade
      3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a
      significant inverse association was discovered between Dose/BW and the
      probability of major molecular response (BCR-ABL1/ABL1 <= 0.1%) when controlled
      for sex (P = 0.033). Moreover, frequent dose interruptions and reductions
      secondary to radotinib toxicities occurred in the Phase 3 study, resulting in
      nearly half (44%) of patients receiving a reduced dose at a 12-month follow-up.
      In conclusion, the results of this study demonstrate the need for initial
      radotinib dose attenuation to improve the long-term efficacy and safety of
      radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once
      daily be tested in patients with newly diagnosed CP-CML.

PMID- 29577682
TI  - [Physiological changes of Saccharomyces cerevisiae during serial re-pitching: a
      review].
AB  - The morphological structure and physiological indexes of Saccharomyces cerevisiae
      have changed during serial re-pitching due to the stress conditions in serial
      handlings and the cells become aging. It is of great significance to study the
      physiological changes of S. cerevisiae during serial re-pitching to understand
      the anti-aging effect of S. cerevisiae. In this paper, the changes of the
      physiological indexes during re-pitching of yeast are summarized, and based on
      the analysis of the previous works further research directions are proposed.

PMID- 29577683
TI  - [Detection of biofilms formation by electrochemical impedance spectroscopy].
AB  - Biofilms are microbial communities composed of bacteria cells and self-produced
      extracellular polymeric substances and lead to antibiotic resistance, forming a
      great threat in the fields of medicine, food industries and so on. The formation
      of biofilms is a multi-stage dynamic process regulated by multiple mechanisms.
      Recently, researchers paid much more attention to the related research areas of
      biofilms, especially the detection methods of biofilms. This paper introduced the
      characteristics and formation process of biofilms as well as the effects of
      quorum sensing on biofilms development. Meanwhile, we discussed the detection
      methods of biofilms, especially electrochemical impedance spectroscopy (EIS) in
      detection of biofilms in detail. Furthermore, we reviewed and predicted that
      microfluidic chips based EIS served as an in-situ and online monitoring method
      for biofilms growth.

PMID- 29577684
TI  - [Advances in mesenchymal to epithelial transition factor signaling pathway and
      inhibitors].
AB  - As a receptor tyrosine kinase, mesenchymal to epithelial transition factor (MET)
      is the membrane receptor for hepatocyte growth factor (HGF), which is related
      with a series of biological functions, such as cell proliferation, progression,
      apoptosis, metastasis and morphological changes. As research continues, MET is
      amplified or overexpressed in a wide range of human cancers and closely related
      with worse prognosis. Therefore, various MET inhibitors are currently being
      developed as potential treatments for a variety of cancers. Based on our current
      study we summarize the existing knowledge on structure, biological function and
      its inhibitors of MET and provide a data phase for future researchers.

PMID- 29577685
TI  - [Progress in the effect of polyamines on proteins].
AB  - Polyamines are a kind of aliphatic amines that exist widely in nearly all
      organisms. Polyamines interact with biological macromolecules through ionic
      interactions and hydrogen bonds, thereby they could affect the cell growth via
      regulating the function of macro-molecules. The impact of polyamines on nucleic
      acids has been thoroughly studied. However, their effects on protein structure
      and functions are not well established. This review summarizes the recent
      progress on how polyamines affect proteins, including metabolic enzymes, ion
      channel proteins and other important proteins. The interaction between polyamines
      and proteins is discussed, and the review also summarizes the challenges in
      studying polyamine-protein interaction as well as the potential application of
      these studies on the therapy of correlated diseases.

PMID- 29577686
TI  - [Advances of long-acting recombinant protein therapeutics].
AB  - Some of the recombinant protein therapeutics with short half-life requires high
      frequent dose or injection, which results in poor patient compliance. This
      challenge has prompted the development of long-acting recombinant proteins in
      recent years. Four strategies and methods, including chemical modification,
      protein engineering, fusion proteins and protein glycosylation are used to modify
      protein molecule and finally obtain improved pharmacokinetics (PK) properties.
      This article reviews the four strategies of half-life extension and presents a
      detailed list of long-acting therapeutics on US, EU and China markets.

PMID- 29577687
TI  - [METTL3 regulates expression of pluripotent genes in porcine pluripotent stem
      cells].
AB  - In post-transcriptional mRNA modification, m6A has been observed in a wide range
      of eukaryotes. METTL3, as a component of methyltransferase complex for m6A
      modification, regulates mouse naive pluripotency and influences mRNA stability,
      especially affecting the expression level of the key pluripotent transcription
      factors. To reveal the expression pattern of the porcine METTL3 gene, we analyzed
      METTL3 expression level in different porcine tissues, somatic cells, and induced
      pluripotent stem cells (piPSCs) by RT-PCR. To identify the function of METTL3 for
      regulation of the expression of porcine pluripotent genes, we cloned a 1 859-bp
      coding sequence of METTL3 and synthesized a shRNA against METTL3. When knocking
      down METTL3 expression in piPSCs, the cell type of piPSCs became naive-like
      morphology, alkaline phosphatase activity was increased, and expression level of
      pluripotent genes NANOG, OCT4 and LIN28A was significantly elevated. In addition,
      piPSCs cultured in medium containing 10 mmol/L cycloleucine for 48 h exhibited
      the similar result as that knocked down METTL3. These findings set the stage for
      optimization of piPS culture condition and further study on the roles of m6A in
      piPSCs.

PMID- 29577688
TI  - [Co-expression of beta-glucosidase and Vitreoscilla hemoglobin in Escherichia
      coli].
AB  - In producing recombinant beta-glucosidase in Escherichia coli by high-cell
      density cultivation (HCDC), insufficient soluble oxygen is always a problem. To
      address it, Vitreoscilla hemoglobin (VHb) was introduced into Escherichia coli by
      the bicistron and T7 promoter expression systems, to improve soluble oxygen by
      bacterial cells and thereby to enhance the biomass and recombinant beta
      glucosidase production. In the case of bicistron expression system, cell density
      in shaking flask reached OD600=(4.24+/-0.29), 35.03% higher than that of the
      control without VHb. Correspondingly, the maximum activity of beta-glucosidase co
      expressed with VHb was (9.78+/-0.55) U/mL, 25.38% higher than that of the
      control. In a 3-L fermentor, the maximum activity of beta-glucosidase was 141.23
      U/mL, 35.57% higher than that of the control. In contrast, the activity of beta
      glucosidase co-expressed with VHb under T7 promoter was lower than that of the
      control, either in flask or in fermentor. Co-expressing beta-glucosidase with VHb
      using the bicistron expression system may improve the tolerance of E. coli to
      insufficient soluble oxygen and thus promote the bacterial biomass and the enzyme
      yield.

PMID- 29577689
TI  - [Control of acetic acid metabolism of recombinant Yarrowia lipolytica for
      efficient succinic acid production].
AB  - Succinic acid is a high value-added organic acid widely used in food, chemical
      and pesticide industries. As a new robust non-conventional yeast, Yarrowia
      lipolytica attracts more and more attention due to its potential for industrial
      applications. Previously, we obtained a succinic acid-producing strain through
      gene deletion of succinic acid dehydrogenase subunit encoding gene Ylsdh5,
      resulting in the strain of PGC01003. However, the recombinant strain produced
      large amount of acetic acid due to imbalance between glycolysis and TCA cycle
      which hindered the efficient production of succinic acid. PDH bypass was
      interfered to decrease the overflow of acetic acid and produce succinic acid
      under natural pH. Acetic acid was reduced to 4.6 g/L through heterologous
      expression of acetyl coenzyme A synthase from Salmonella enteric, which was 75.4%
      of the control strain. Deletion of CoA-transferase gene Ylach1 eliminated acetate
      formation and improved succinic acid production, and the resulting strain
      produced as high as 7.0 g/L succinic acid. Our study provides foundation for
      further construction of efficient cell factory of succinic acid production.

PMID- 29577690
TI  - [PDGF-B immunogen preparation and the suppressive effect of anti-PDGF-B ascite
      antibody on the proliferation of hepG2 cells].
AB  - To observe the immunogenicity of hPDGF-B immunogens that were synthesized with
      the fusional expression vector pET28-Trx and to test the suppressive effect of
      these specific antibodies induced by both of immunogens on proliferation of human
      HepG2 hepatoma cells. First, we chose 2 antigenic epitopes hPDGF-BDelta103-118aa
      and hPDGF-BDelta152-167aa from human PDGF-B and inserted these 2 coding regions
      into the empty vector plasmid pET28-Trx, separately. Second, mice were immunized
      with purified recombinant proteins to generate polyclonal antibody. Then we
      intraperitoneally injected mice bearing hepatoma 22 (H22) tumor cells to prepare
      antibody ascites. ELISA and Western blot were used to detect the titer and the
      utility of the antibody, respectively. Finally, HepG2 cells were exposed to PDGF
      BB protein or anti-PDGF-B ascite antibody in different dilution concentrations
      groups and the proliferation of HepG2 cells was quantified by CCK8 assay. As the
      results, we identified mice that could produce high drop of neutralizing
      antibodies against hPDGF-B induced by both two recombinant proteins. Two anti
      PDGF-B ascite antibodies could markedly inhibit the proliferation of HepG2 cells
      by blocking the stimulating effect of PDGF-BB protein. Our results suggest that
      Trx-PDGF-B recombinant protein as immunogen provides a new method for the
      preparation of PDGF-B vaccine, and also a new idea for the treatment of
      hepatocellular carcinoma in clinical practice.

PMID- 29577691
TI  - [Detection of KRAS mutation in colorectal cancer patients' cfDNA with droplet
      digital PCR].
AB  - This study aims to develop a new method for the detection of KRAS mutations
      related to colorectal cancer in cfDNA, and to evaluate the sensitivity and
      accuracy of the detection. We designed a method of cfDNA based KRAS detection by
      droplets digital PCR (ddPCR). The theoretical performance of the method is
      evaluated by reference standard and compared to the ARMS PCR method. Two methods,
      ddPCR and qPCR, were successfully established to detect KRAS wild type and 7
      mutants. Both methods were validated using plasmid standards and actual samples.
      The results were evaluated by false positive rate, linearity, and limit of
      detection. Finally, 52 plasma cfDNA samples from patients and 20 samples from
      healthy people were tested, the clinical sensitivity is 97.64%, clinical
      specificity is 81.43%. ddPCR method shows higher performance than qPCR. The LOD
      of ddPCR method reached single digits of cfDNA copies, it can detect as low as
      0.01% to 0.04% mutation abundance.

PMID- 29577692
TI  - [Cloning of Oryza sativa N-glycanase gene (OsPNGase A) and its expression in
      Pichia pastoris].
AB  - N-glycanase is a class of deglycosylation enzymes, widely used in the study of N
      glycosylation modification of glycoprotein. In this study, an N-glycanase gene
      (OsPNGase A, XM_015775832) with high GC content (69.48%) was cloned from rice and
      then the yeast secretory expression vector pPICZ(alpha)A-OsPNGase A was
      constructed for the purpose of transformation to Pichia pastoris. After induction
      in Pichia pastoris SMD1168H, the target protein was purified by DEAE Sepharose
      and HisTrap HP chromatography, with a yield of 12.3 mg OsPNGase A from 1 L
      fermentation medium, showing a specific activity of 258 U/mg. SDS-PAGE revealed
      that the purified OsPNGase A was a single band and showed consistentcy with the
      expected molecular weight. OsPNGase A could act on transferrin recombinantly
      expressed in rice, avidin recombinantly expressed in corn and horseradish
      peroxidase. Furthermore, OsPNGase A showed higher activity than commercial PNGase
      F towards avidin. OsPNGase A displayed the highest digestion activity at pH 6.0
      and 40  degrees C, and was also active in the neutral and alkaline environment.
      Despite the fact that OsPNGase A was inhibited by reducing agents and
      surfactants, it still maintained partial enzymatic activity in 100 mmol/L beta-ME
      or DTT. Therefore, the successful expression of rice OsPNGase A provides a new
      tool for the study of plant glycoproteins and the establishment of yeast
      secretion expression system lays the foundation for the preparation of PNGase A.

PMID- 29577693
TI  - [Tat-based cell-cell fusion method for screening HIV-1 fusion inhibitors].
AB  - An HIV-1 cell-cell fusion system was developed to screen HIV-1 entry inhibitors
      that block cell-cell fusion. In this system, the pEGFP-Tat plasmid was
      constructed and cotransfected into effector cells (HEK-293T) with HIV-1 envelope
      plasmid. TZM-bl cell, a genetically engineered cell line that expresses CD4,
      CXCR4, CCR5 as well as Tat-inducible beta-galactosidase and luciferase reporter
      gene, was used as target cell. Thus, the co-culture of target cells and effector
      cells allows the cell fusion via Env and the activity of the fusion inhibitor can
      be quantified by measuring the reporter protein expression. The experimental
      parameters were optimized and 11 anti-HIV-1 agents including CCR5 antagonist
      maraviroc, reverse transcription inhibitor zidovudine (AZT) and integrase
      inhibitor raltegravir were tested. The result showed that the system exhibited
      high specificity and sensitivity. Two of eight tested anti-HIV-1 agents were
      found to block the cell-cell fusion. The system is suitable for efficient
      screening of HIV-1 cell-cell fusion inhibitors.

PMID- 29577694
TI  - [Detection of procalcitonin based on fluorescence immune chromatography].
AB  - Procalcitonin (PCT) is the precursor of calcitonin related to the severity of
      human bacterial infection. We made a test strip by coupling anti-PCT to quantum
      dot, in order to develop a highly sensitive and convenient PCT testing product.
      The anti-PCT titer had reached 107 because of the stability by coupling anti-PCT
      with quantum dot. The detecting linear range of the experiment was 0.15 to 120
      MUg/L, the sensitivity was 0.007 MUg/L, the recovery range was 91% to 113%, and
      the intra- and inter-assay coefficient of variation was less than 8%. Comparing
      the homemade fluorescence-detected test strip with PCT ELISA kit on sale, we got
      accurate results which could mostly accomplish the test of clinical samples.

PMID- 29577695
TI  - [Enhancer trapping nearby rps26 gene in zebrafish mediated by the Tol2 transposon
      and it's annotation].
AB  - With the completion of large-scale genome sequencing of human beings and other
      organisms, understanding the expression of control elements on the genome has
      become an important research task in the post-genome era. The enhancer trapping
      technology is an effective method for identifying enhancer elements in the genome
      and understanding its mechanism for gene expression regulation. In this study, we
      selected the stable enhancer trapping line TK4 (head and trunk specific GFP
      expression), which is generated with the mediation of Tol2 transposon system, and
      analyzed the trapped enhancers with the techniques of Splinkerette PCR (sp-PCR),
      in situ hybridization and comparative genomics. We crossed F1 individuals of TK4
      line with wild-type zebrafish, collected fertilized eggs, and then detected the
      expression pattern of green fluorescent protein reporter gene by fluorescence
      microscopy at six different developmental stages, 6 hpf (hour post
      fertilization), 24 hpf, 48 hpf, 3 dpf (day post fertilization), 4 dpf and 5 dpf .
      The zebrafish genome flank sequence near the insertion site of Tol2 transposon
      was cloned by sp-PCR, and the results revealed that the insertion located at the
      position 27749253 of chromosome 23, and the transgene inserted reversely inside
      the intron 1 of rps26 gene. Within the 100 kb region of the insertion site,
      totally, seven genes including arf3a, wnt10b, wnt1, rps26, IKZF4, dnajc22 and
      lmbr1l were identified. Comparative genomic analysis by VISTA program revealed
      that there were two potential enhancer elements in the downstream of rps26 gene,
      which were conserved non-coding sequence (CNS) 1 and CNS2. The results of in situ
      hybridization showed that two transcripts of rps26 gene were maternal expression,
      the expression of rps26-201 in zygote was earlier than that of rps26-001, and the
      GFP signal of TK4 line zebrafish was not detectable before 6hpf, the expression
      patterns of rps26 and GFP at the late stages display similarity, and also
      represent differences, which suggested that the expression of rps26 and GFP may
      be controlled by the same enhancer, and also by the different enhancer, and two
      potential enhancers (CNS1 and CNS2) may play a differential regulation roles on
      the spatial and temporal expression of nearby genes (including rps26). In this
      study, we successfully obtained two potential enhancers near rps26 gene for the
      first time, which laid a foundation for further study of the regulation mechanism
      between these two enhancers and nearby genes in the genome, and the combination
      technique used in this study also provides a reference for enhancer analysis.

PMID- 29577696
TI  - [Establishment of the Mathematical Model for PMI Estimation Using FTIR
      Spectroscopy and Data Mining Method].
AB  - OBJECTIVES: To analyse the relationship between Fourier transform infrared (FTIR)
      spectrum of rat's spleen tissue and postmortem interval (PMI) for PMI estimation
      using FTIR spectroscopy combined with data mining method. METHODS: Rats were
      sacrificed by cervical dislocation, and the cadavers were placed at 20 C. The
      FTIR spectrum data of rats' spleen tissues were taken and measured at different
      time points. After pretreatment, the data was analysed by data mining method.
      RESULTS: The absorption peak intensity of rat's spleen tissue spectrum changed
      with the PMI, while the absorption peak position was unchanged. The results of
      principal component analysis (PCA) showed that the cumulative contribution rate
      of the first three principal components was 96%. There was an obvious clustering
      tendency for the spectrum sample at each time point. The methods of partial least
      squares discriminant analysis (PLS-DA) and support vector machine classification
      (SVMC) effectively divided the spectrum samples with different PMI into four
      categories (0-24 h, 48-72 h, 96-120 h and 144-168 h). The determination
      coefficient (R2) of the PMI estimation model established by PLS regression
      analysis was 0.96, and the root mean square error of calibration (RMSEC) and root
      mean square error of cross validation (RMSECV) were 9.90 h and 11.39 h
      respectively. In prediction set, the R2 was 0.97, and the root mean square error
      of prediction (RMSEP) was 10.49 h. CONCLUSIONS: The FTIR spectrum of the rat's
      spleen tissue can be effectively analyzed qualitatively and quantitatively by the
      combination of FTIR spectroscopy and data mining method, and the classification
      and PLS regression models can be established for PMI estimation.

PMID- 29577697
TI  - [Relationship between FoxO1 Expression and Wound Age during Skin Incised Wound
      Healing].
AB  - OBJECTIVES: To investigate FoxO1 expression and its time-dependent changes during
      the skin incised wound healing. METHODS: After the establishment of the skin
      incised wound model in mice, the FoxO1 expression of skin in different time
      periods was detected by immunohistochemistry and Western blotting. RESULTS:
      Immunohistochemistry staining showed that FoxO1 was weakly expressed in a few
      fibroblasts of epidermis, hair follicles, sebaceous glands, vessel endothelium
      and dermis in the control group. The FoxO1 expression was enhanced in the
      epidermis and skin appendages around the wound during 6-12 h after injury, which
      could be detected in the infiltrating neutrophils and a small number of
      monocytes. FoxO1 was mainly expressed in monocytes during 1-3 d after injury, and
      in neovascular endothelial cells and fibroblasts during 5-10 d. On the 14th day
      after injury, the FoxO1 expression still could be detected in a few fibroblasts.
      The Western blotting results showed that the FoxO1 expression quantity of the
      tissue samples in injury group was higher than in control group. The FoxO1
      expression peaked at 12 h and 7 d after injury. CONCLUSIONS: FoxO1 is time
      dependently expressed in skin wound healing, which can be a useful marker for
      wound age determination.

PMID- 29577698
TI  - [Application of Mixed-effect Model in PMI Estimation by Vitreous Humor].
AB  - OBJECTIVES: To test the changes of the potassium (K+) and magnesium (Mg2+)
      concentrations in vitreous humor of rabbits along with postmortem interval (PMI)
      under different temperatures, and explore the feasibility of PMI estimation using
      mixed-effect model. METHODS: After sacrifice, rabbit carcasses were preserved at
      5 C, 15 C, 25 C and 35 C, and 80-100 MUL of vitreous humor was collected by the
      double-eye alternating micro-sampling method at every 12 h. The concentrations of
      K+ and Mg2+ in vitreous humor were measured by a biochemical-immune analyser. The
      mixed-effect model was used to perform analysis and fitting, and established the
      equations for PMI estimation. The data detected from the samples that were stoned
      at 10 C, 20 C and 30 C with 20, 40 and 65 h were used to validate the equations
      of PMI estimation. RESULTS: The concentrations of K+ and Mg2+ [f(x,y)] in
      vitreous humor of rabbits under different temperature increased along with PMI
      (x). The relative equations of K+ and Mg2+ concentration with PMI and temperature
      under 5 C~35 C were fK+(x,y)=3.413 0+0.309 2 x+0.337 6 y+0.010 83 xy-0.002 47 x2
      (P<0.000 1), and fMg2+(x,y)=0.745 6+0.006 432 x+0.033 8 y (P<0.000 1),
      respectively. It was proved that the time of deviation for PMI estimation by K+
      and Mg2+ was in 10 h when PMI was between 0 to 40 h, and the time of deviation
      was in 21 h when PMI was between 40 to 65 h. CONCLUSIONS: the ambient temperature
      range of 5 C-35 C, the mixed-effect model based on temperature and vitreous humor
      substance concentrations can provide a new method for the practical application
      of vitreous humor chemicals for PMI estimation.

PMID- 29577699
TI  - [Time-dependent Expression of Nrf2 Protein and its Effects on Wound Repair in
      Skeletal Muscle].
AB  - OBJECTIVES: To detect the expression of nuclear factor erythroid 2-related factor
      2 (Nrf2) to explore its change rule and effects in the repair process of skeletal
      muscle. METHODS: An injury model of skeletal muscle was established by injection
      of cardiotoxin into the gastrocnemius muscle of SD male rats. The muscle samples
      were taken from control group and injury group at each time point (1 h, 4 h, 8 h,
      12 h, 16 h, 1 d, 3 d, 5 d, 7 d, 9 d, 13 d, 17 d, 21 d). The morphological changes
      of skeletal muscle in repair process were observed by HE staining, and the
      content of reactive oxygen species (ROS) was detected. The expression level of
      Nrf2 protein was investigated by Western blotting and immunohistochemistry
      staining. RESULTS: After the skeletal muscle injury, the injury region was
      infiltrated with inflammatory cells which constituted mainly by lymphocyte
      neutrophils and mononuclear cells. There were large amounts of immature muscle
      cells appeared at the 5th day and the muscle repair was completed at the 21th
      day. Comparing with control group, the ROS content decreased in injury group at
      the 12th hour (P<0.05), while Nrf2 expression increased at the 16th hour
      (P<0.05). Moreover, the positive rate of Nrf2 increased after injury, and peaked
      at 16 h-1 d, then decreased gradually and returned to the level of control group
      (P<0.05). CONCLUSIONS: The Nrf2 protein involves in the regulation of the repair
      of skeletal muscle injury. The positive rate of Nrf2 shows a time-dependent
      expression, which can be used to estimate the wound age of skeletal muscle.

PMID- 29577700
TI  - [Stature Estimation for Sichuan Han Female Based on Whole-spine X-ray Photo-
      graphy].
AB  - OBJECTIVES: To establish regression models of stature estimation for Sichuan Han
      female by the measurement of total vertebral column length in the frontal and
      lateral X-ray films of whole-spine. METHODS: The frontal and lateral X-ray films
      of whole-spine were collected from 200 Sichuan Han females by large flat-panel
      multi-functional universal radiography and fluoroscopy system. The data and mean
      values of frontal and lateral total vertebral column length were measured and
      calculated in all the samples, respectively. The relationship of combined multi
      markers and stature were analysed by linear regression analysis, and the
      mathematical models of stature estimation were established. The data of 30 new
      samples were selected and inputted for verifying the accuracy of the mathematical
      models. RESULTS: The total vertebral column length showed a good correlation with
      stature, and the mean values of the frontal and lateral X-ray films of total
      vertebral column length had the highest correlation coefficients. Three
      established linear regression equation models were statistically significant
      (P<0.05), and the equation established with lateral total vertebral column length
      showed the highest accuracy. CONCLUSIONS: The stature estimation by the
      measurement of total vertebral column length has high accuracy.

PMID- 29577701
TI  - [Automated Assessment for Bone Age of Left Wrist Joint in Uyghur Teenagers by
      Deep Learning].
AB  - OBJECTIVES: To realize the automated bone age assessment by applying deep
      learning to digital radiography (DR) image recognition of left wrist joint in
      Uyghur teenagers, and explore its practical application value in forensic
      medicine bone age assessment. METHODS: The X-ray films of left wrist joint after
      pretreatment, which were taken from 245 male and 227 female Uyghur nationality
      teenagers in Uygur Autonomous Region aged from 13.0 to 19.0 years old, were
      chosen as subjects. And AlexNet was as a regression model of image recognition.
      From the total samples above, 60% of male and female DR images of left wrist
      joint were selected as net train set, and 10% of samples were selected as
      validation set. As test set, the rest 30% were used to obtain the image
      recognition accuracy with an error range in +/-1.0 and +/-0.7 age respectively,
      compared to the real age. RESULTS: The modelling results of deep learning
      algorithm showed that when the error range was in +/-1.0 and +/-0.7 age
      respectively, the accuracy of the net train set was 81.4% and 75.6% in male, and
      80.5% and 74.8% in female, respectively. When the error range was in +/-1.0 and
      +/-0.7 age respectively, the accuracy of the test set was 79.5% and 71.2% in
      male, and 79.4% and 66.2% in female, respectively. CONCLUSIONS: The combination
      of bone age research on teenagers' left wrist joint and deep learning, which has
      high accuracy and good feasibility, can be the research basis of bone age
      automatic assessment system for the rest joints of body.

PMID- 29577702
TI  - [Comparison of Bacteria ERIC-PCR Fingerprints of Index Fingers and Contactants].
AB  - OBJECTIVES: To explore the bacteria relevance between index fingers and
      contactant' surfaces (mobile phone touch screen and desktop of personal office
      table). METHODS: Bacteria were collected from the index fingers, mobile phone
      touch screen and desktop of personal office table of 10 volunteers.
      Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprint was
      established by PCR amplification technique of metagenome. RESULTS: There were 7
      volunteers' ERIC-PCR fingerprints of index fingers matched that took from the
      mobile phone touch screens, and different from each other. There were 3
      volunteers' ERIC-PCR fingerprints of index fingers matched that took from desk
      top of personal office table, and other 7 volunteers' ERIC-PCR fingerprints did
      not match perfectly with that took from desk top of personal office table, but
      had at least one similar band for both. CONCLUSIONS: The bacteria on index finger
      shows individual specificity, which on mobile phone touching screen and personal
      desktop may be a new biological sample of forensic identification.

PMID- 29577703
TI  - [Analysis of Arsenic Compounds in Blood and Urine by HPLC-ICP-MS].
AB  - OBJECTIVES: To establish an analysis method for the detection of 6 arsenic
      compounds [AsC, AsB, As(III), DMA, MMA and As(V)] in blood and urine by high
      performance liquid chromatography-inductively coupled plasma-mass spectrometry
      (HPLC-ICP-MS), and apply it to real cases. METHODS: Triton was used to damage
      cells, and then EDTA.2Na.2H2O was used to complex arsenic compounds in cells, and
      sonication and protein deposition by acetonitrile were performed for sample
      pretreatment. With the mobile phase consisted of ammonium carbonate and ultrapure
      water, gradient elution was performed for obtaining the arsenic compounds in
      samples, which were analysed by ICP-MS with Hamilton PRP-X100 column. RESULTS:
      The limits of detection in blood were 1.66-10 ng/mL, while the lower limits of
      quantitation in blood ranged from 5 to 30 ng/mL. The limits of detection in urine
      were 0.5-10 ng/mL, while the lower limits of quantitation in urine were 5-30
      ng/mL. The relative standard deviation of inter-day and intra-day precisions was
      less than 10%. This method had been successfully applied to 3 cases. CONCLUSIONS:
      This study has established an analysis method for detecting 6 common arsenic
      compounds in blood and urine, which can be used to detect the arsenic compounds
      in the blood and urine from arsenic poisoning cases as well as the patients under
      arsenic treatment.

PMID- 29577704
TI  - [Application of Activities of Daily Living Scale in Mild Psychiatric Impairment
      Assessment].
AB  - OBJECTIVES: To explore the application of activities of daily living (ADL) scale
      in mild psychiatric impairment assessment under the guideline of Classification
      of Human Body Disability Caused by Injury. METHODS: A total of 124 subjects with
      organic mental disorders and mild psychiatric impairments (levels 7 to 10), and
      106 healthy controls were included in. All participants were assessed by the ADL
      scale, physical self-maintenance scale (PSMS) and instrumental activities of
      daily living (IADL) scale. The difference between the scores of control group and
      study group, and the relationship of impairment level and the scores were
      compared, and the threshold value was determined according to the ROC curve.
      RESULTS: The total scores of ADL, IADL and PSMS were significantly different
      between the control group and the study group (P<0.05). The scores of ADL, IADL,
      PSMS were significantly different among the impairment levels (P<0.05), which
      showed a relativity with impairment level. The scores of ADL corresponding to
      levels 10, 9, 8 and 7 were 14-17, 18-23, 24-29 and 30-34, respectively, which
      showed a good correlation between the conclusion according to the scale and the
      expert's opinion (kappa= 0.914, P<0.05). CONCLUSIONS: The score of ADL was
      significantly related to mild psychiatric impairment, and the higher ADL score
      represents the more severe disability, which can be used as a reference index for
      preliminarily judging the level of mild psychiatric impairment.

PMID- 29577705
TI  - [Research Progress of Vitreous Humor Detection Technique on Estimation of
      Postmortem Interval].
AB  - Estimation of postmortem interval (PMI) plays a crucial role in forensic study
      and identification work. Because of the unique anatomy location, vitreous humor
      is considered to be used for estima- ting PMI, which has aroused interest among
      scholars, and some researches have been carried out. The detection techniques of
      vitreous humor are constantly developed and improved which have been gradually
      applied in forensic science, meanwhile, the study of PMI estimation using
      vitreous humor is updated rapidly. This paper reviews various techniques and
      instruments applied to vitreous humor detection, such as ion selective electrode,
      capillary ion analysis, spectroscopy, chromatography, nano-sensing technology,
      automatic biochemical analyser, flow cytometer, etc., as well as the related
      research progress on PMI estimation in recent years. In order to provide a
      research direction for scholars and promote a more accurate and efficient
      application in PMI estimation by vitreous humor analysis, some inner problems are
      also analysed in this paper.

PMID- 29577706
TI  - [Research Progress on Determination of Drowning Site].
AB  - The bodies found in water are one of the most common types in forensic practice.
      The discovery site of the body is often not the drowning site. However, the
      determination of drowning site is vital for the identification of victim.
      Inorganic particles and planktons, such as granular impurities, diatoms and
      bacteria, are valuable markers for the diagnosis of drowning. By comparing the
      granular impurities and planktons in tissues and suspicious drowning mediums, the
      drowning site can be concluded based on their similarity of types and
      distribution, which has practical applied value. In this paper, the research
      progress on determination of drowning site is summarized to provide reference for
      the peers.

PMID- 29577707
TI  - [Research Progress and Forensic Application on the Pathogenesis of Coronary
      Artery Spasm].
AB  - Coronary artery spasm (CAS) is a hyper-contraction of segmental coronary artery
      in response to multiple stimuli. At present, it's still in lack of specific
      diagnostic indicators of sudden cardiac death caused by CAS. This review
      summarizes current researches on the mechanisms of CAS and describes the roles of
      vascular endothelial dysfunction and vascular smooth muscle hypersensitivity in
      the course of CAS. Furthermore, the molecular mechanisms of the endogenous NO and
      endothelin-1 cause vascular endothelial dysfunction, and the phosphorylation of
      MLC2, Rho kinase and endoplasmic reticulum stress related to vascular smooth
      muscle hypersensitivity are discussed. Meanwhile, the possibility of forensic
      application for the related molecules on the diagnosis of sudden cardiac death
      caused by CAS are also explored.

PMID- 29577708
TI  - [Research Progress of the Effects of Monocular Visual Impairment on Binocular
      Vision].
AB  - Binocular vision refers to a progress of analysing and integrating the binocular
      visual signals into a whole and three-dimensional sensory perception by higher
      nerve centre. In this process, the interac- tion between the two eyes results in
      the changes of output signal, which is called binocular interaction. Through a
      series of subjective and objective experiments, it can be concluded that
      binocular interaction can be divided into three types: facilitation, summation
      and suppression, and the forms of binocular interaction in different visual
      states are different. In general, the visual signal is processed by binocular
      interaction, so that there are some differences between binocular vision and
      monocular vision. The extent of the difference can be affected by the damage of
      monocular vision and then affects the binocular vision. Thus, it is necessary for
      forensic scientists to further study the effects of the monocular visual
      impairment on visual function. Based on relevant data, this paper reviews the
      mechanism of the monocular visual impairment in binocular vision, the research
      methods and the application prospect in forensic science.

PMID- 29577709
TI  - [Research Progress of CircRNA and Its Application Prospect in Forensic Medicine].
AB  - Circular RNA (circRNA) is a type of noncoding RNA with tissue specificity and
      high stability, which forms a closed continuous loop and is abundantly expressed
      in tissue cells. According to recent research, the regulatory function of circRNA
      elucidating in the occurrence and development of disease shows a potential for
      diagnosing clinical disease and revealing disease mechanism. This paper reviews
      the biological characteristics, analysis methods of circRNA and its research
      progress in clinical application as biomarker, and outlooks its application in
      the field of forensic medicine.

PMID- 29577710
TI  - Etiological periodontal treatment with and without low-level laser therapy on IL
      1beta level in gingival crevicular fluid: an in vivo multicentric pilot study.
AB  - Cytokine proteins may have important roles during different human physiological
      and pathological processes. In the oral cavity, the bone loss and periodontal
      tissue pathology was related to inflammatory process activation. The aim of the
      present study was to assess the effects of etiological periodontal therapy with
      and without the use of Low Level Laser Therapy (LLLT) on clinical periodontal
      parameters and interleukin (IL)-1beta level in gingival crevicular fluid (GCF)
      from chronic periodontitis (CP) patients. Thirty non-smoker CP patients were
      selected from the Foggia University Dental Clinic and other 2 private dental
      clinics. All patients were divided into two homogeneous randomized groups: 15
      patients were treated with only scaling and root planing (group 1) and 15
      patients with scaling and root planing etiological treatment and LLLT (group 2).
      In all sites, at baseline before treatment, the periodontal pocket depth (PPD)
      and bleeding on probing (BOP) were measured. In the PPD sites, the GCF samples
      were collected from 30 deep (>=5 mm) and shallow (<=3 mm) sites and IL-1beta were
      evaluated at baseline, after 10 days and 1 month. In all the samples at baseline,
      the IL-1beta concentration in GCF and BOP rate were significantly higher at deep
      PPD sites than at the shallow ones. After 10 days in all samples no PPD
      improvement was observed in the BOP rate but the IL-1 beta level was
      statistically significantly improved (p<0.005) in group 2 compared to group 1. At
      10 days and 1 month, in all deep PPD sites, PPD and BOP improvements were
      observed. At same time, IL-1beta levels were lower and statistically
      significantly (p<0.005) improved in group 2 compared to group 1. The results
      confirmed that the periodontal etiology treatment of deep PPD sites with or with
      out associated LLLT promotes periodontal health. Etiological treatment associated
      with LLLT, improves BOP and inflammation in periodontal disease. Moreover, the IL
      1beta concentration changes in GCF suggest these cytokines as a predictable
      marker of gingival inflammation in chronic periodontitis patients.

PMID- 29577711
TI  - IL-1 haplotype analysis in periodontal disease.
AB  - Numerous studies have established statistical associations of the IL-1 gene
      cluster polymorphisms with various inflammatory diseases. Deriving from that, the
      present study was intended to determine whether single-nucleotide polymorphisms
      (SNPs) in these gene are also associated with periodontal disease in a Linkage
      disequilibrium analysis. This investigation also created two haplotype blocks,
      both consisting of two different SNPs. Recent theoretical analyses indicate that
      research with an interpretation of periodontal disease as a complex, oligogenic
      disorder, with IL-1 genetic variation contributes an important but not exclusive
      influence on disease risk. Further studies are needed to confirm these results
      and to understand the mechanisms behind the observed association between IL-1
      SNPs and periodontal disease.

PMID- 29577714
TI  - Effects of Melanin on Optical Behavior of Polymer: From Natural Pigment to
      Materials Applications.
AB  - Melanin is a kind of ubiquitous natural pigment, which serves a variety of
      protective functions in many organisms. In the present study, natural melanin and
      synthetic melanin nanoparticles (NPs) were systematically investigated for its
      potential application in polymeric optical materials. A significant short
      wavelength shielding and high visible light transparency polymer nanocomposite
      was easily obtained via tuning the melanin particle size. In particular, the
      nanocomposite film with melanin NPs (diameter ~ 15 nm) loading even as low as 1
      wt % blocks most ultraviolet light below 340 nm and still keeps high visible
      light transparency (83%) in the visible spectrum. More importantly, because of
      the excellent photoprotection and radical scavenging capabilities of melanin, the
      resulting polymer nanocomposite exhibits outstanding photostability. In effect,
      such fantastic melanin NPs is promising for applications in various optical
      materials.

PMID- 29577715
TI  - The Nonbilayer Lipid MGDG and the Major Light-Harvesting Complex (LHCII) Promote
      Membrane Stacking in Supported Lipid Bilayers.
AB  - The thylakoid membrane of algae and land plants is characterized by its intricate
      architecture, comprising tightly appressed membrane stacks termed grana. The
      contributions of individual components to grana stack formation are not yet fully
      elucidated. As an in vitro model, we use supported lipid bilayers made of
      thylakoid lipid mixtures to study the effect of major light-harvesting complex
      (LHCII), different lipids, and ions on membrane stacking, seen as elevated
      structures forming on top of the planar membrane surface in the presence of LHCII
      protein. These structures were examined by confocal laser scanning microscopy,
      atomic force microscopy, and fluorescence recovery after photobleaching,
      revealing multilamellar LHCII-membrane stacks composed of connected lipid
      bilayers. Both native-like and non-native interactions between the LHCII
      complexes may contribute to membrane appression in the supported bilayers.
      However, applying in vivo-like salt conditions to uncharged glycolipid membranes
      drastically increased the level of stack formation due to enforced LHCII-LHCII
      interactions, which is in line with recent crystallographic and cryo-electron
      microscopic data [Wan, T., et al. (2014) Mol. Plant 7, 916-919; Albanese, P., et
      al. (2017) Sci. Rep. 7, 10067-10083]. Furthermore, we observed the nonbilayer
      lipid MGDG to strongly promote membrane stacking, pointing to the long-term
      proposed function of MGDG in stabilizing the inner membrane leaflet of highly
      curved margins in the periphery of each grana disc because of its negative
      intrinsic curvature [Murphy, D. J. (1982) FEBS Lett. 150, 19-26].

PMID- 29577716
TI  - Facile Synthesis of Ultrafine Hematite Nanowire Arrays in Mixed Water-Ethanol
      Acetic Acid Solution for Enhanced Charge Transport and Separation.
AB  - Nanostructure engineering is of great significance for semiconductor electrode to
      achieve high photoelectrochemical performance. Herein, we report a novel strategy
      to fabricate ultrafine hematite (alpha-Fe2O3) nanowire arrays in a mixed water
      ethanol-acetic acid (WEA) solvent. To the best of our knowledge, this is the
      first report on direct growth of ultrafine (~10 nm) alpha-Fe2O3 nanowire arrays
      on fluorine-doped tin oxide substrates through solution-based fabrication
      process. The effect of WEA ratio on the morphology of nanowires has been
      systematically studied to understand the formation mechanism.
      Photoelectrochemical measurements were conducted on both Ti-treated alpha-Fe2O3
      nanowire and nanorod photoelectrodes. It reveals that alpha-Fe2O3 nanowire
      electrode has higher photocurrent and charge separation efficiencies than nanorod
      electrode if the carrier concentration and space-charge carrier width are in the
      same order of magnitude. Normalized by electrochemically active surface area, the
      Ti-treated alpha-Fe2O3 nanowire electrode obtains 6.4 times higher specific
      photocurrent density than nanorod electrode. This superiority of nanowires arises
      from the higher bulk and surface charge separation efficiencies, which could be
      partly attributed to reduced distance that holes must transfer to reach the
      semiconductor-liquid junction.

PMID- 29577717
TI  - Identification of Individual Immobilized DNA Molecules by Their Hybridization
      Kinetics Using Single-Molecule Fluorescence Imaging.
AB  - Single-molecule fluorescence methods can count molecules without calibration,
      measure kinetics at equilibrium, and observe rare events that cannot be detected
      in an ensemble measurement. We employ total internal reflection fluorescence
      microscopy to monitor hybridization kinetics between individual spatially
      resolved target DNA molecules immobilized at a glass interface and fluorescently
      labeled complementary probe DNA in free solution. Using super-resolution imaging,
      immobilized target DNA molecules are located with 36 nm precision, and their
      individual duplex formation and dissociation kinetics with labeled DNA probe
      strands are measured at site densities much greater than the diffraction limit.
      The purpose of this study is to evaluate uncertainties in identifying these
      individual target molecules based on their duplex dissociation kinetics, which
      can be used to distinguish target molecule sequences randomly immobilized in
      mixed-target samples. Hybridization kinetics of individual target molecules are
      determined from maximum likelihood estimation of their dissociation times
      determined from a sample of hybridization events at each target molecule. The
      dissociation time distributions thus estimated are sufficiently narrow to allow
      kinetic discrimination of different target sequences. For example, a single-base
      thymine-to-guanine substitution on immobilized strands produces a 2.5-fold
      difference in dissociation rates of complementary probes, allowing for the
      identification of individual target DNA molecules by their dissociation rates
      with 95% accuracy. This methodology represents a step toward high-density single
      molecule DNA microarray sensors and a powerful tool to investigate the kinetics
      of hybridization at surfaces at the molecular level, providing information that
      cannot be acquired in ensemble measurements.

PMID- 29577719
TI  - Anisamide-Anchored Lyotropic Nano-Liquid Crystalline Particles with AIE Effect: A
      Smart Optical Beacon for Tumor Imaging and Therapy.
AB  - The prospective design of nanocarriers for personalized oncotherapy should be an
      ensemble of targeting, imaging, and noninvasive therapeutic capabilities. Herein,
      we report the development of the inverse hexagonal nano-liquid crystalline (NLC)
      particles that are able to host formononetin (FMN), a phytoestrogen with known
      anticancer activity, and tetraphenylethene (TPE), an iconic optical beacon with
      aggregation-induced emission (AIE) signature, simultaneously. Ordered three
      dimensional mesoporous internal structure and high-lipid-volume fraction of NLC
      nanoparticles (NLC NPs) frame the outer compartment for the better settlement of
      payloads. Embellishment of these nanoparticles by anisamide (AA), a novel sigma
      receptor targeting ligand using carbodiimide coupling chemistry ensured NLC's as
      an outstanding vehicle for possible utility in surveillance of tumor location as
      well as the FMN delivery through active AIE imaging. The size and structural
      integrity of nanoparticles were evaluated by quasi-elastic light scattering, cryo
      field emission scanning electron microscopy small-angle X-ray scattering. The
      existence of AIE effect in the nanoparticles was evidenced through the
      photophysical studies that advocate the application of NLC NPs in fluorescence
      based bioimaging. Moreover, confocal microscopy illustrated the single living
      cell imaging ability endowed by the NLC NPs. In vitro and in vivo studies
      supported the enhanced efficacy of targeted nanoparticles (AA-NLC-TF) in
      comparison to nontargeted nanoparticles (NLC-TF) and free drug. Apparently, this
      critically designed multimodal NLC NPs may establish a promising platform for
      targeted and image-guided chemotherapy for breast cancer.

PMID- 29577718
TI  - Synthesis and Explosion Hazards of 4-Azido-l-phenylalanine.
AB  - A reliable, scalable, cost-effective, and chromatography-free synthesis of 4
      azido-l-phenylalanine beginning from l-phenylalanine is described. Investigations
      into the safety of the synthesis reveal that the Ullman-like Cu(I)-catalyzed
      azidation step does not represent a significant risk. The isolated 4-azido-l
      phenylalanine product, however, exhibits previously undocumented explosive
      characteristics.

PMID- 29577720
TI  - Rational Design of Au@Pt Multibranched Nanostructures as Bifunctional Nanozymes.
AB  - One of the current challenges in nanozyme-based nanotechnology is the utilization
      of multifunctionalities in one material. In this regard, Au@Pt nanoparticles
      (NPs) with excellent enzyme-mimicking activities due to the Pt shell and unique
      surface plasmon resonance features from the Au core have attracted enormous
      research interest. However, the unique surface plasmon resonance features from
      the Au core have not been widely utilized. The practical problem of the optical
      damping nature of Pt hinders the research into the combination of Au@Pt NPs'
      enzyme-mimicking properties with their surface-enhanced Raman scattering (SERS)
      activities. Herein, we rationally tuned the Pt amount to achieve Au@Pt NPs with
      simultaneous plasmonic and enzyme-mimicking activities. The results showed that
      Au@Pt NPs with 2.5% Pt produced the highest Raman signal in 2 min, which
      benefited from the remarkably accelerated catalytic oxidation of 3,3',5,5'
      tetramethylbenzidine with the decorated Pt and strong electric field retained
      from the Au core for SERS. This study not only demonstrates the great promise of
      combining bimetallic nanomaterials' multiple functionalities but also provides
      rational guidelines to design high-performance nanozymes for potential biomedical
      applications.

PMID- 29577721
TI  - Portfolio Optimization of Nanomaterial Use in Clean Energy Technologies.
AB  - While engineered nanomaterials (ENMs) are increasingly incorporated in diverse
      applications, risks of ENM adoption remain difficult to predict and mitigate
      proactively. Current decision-making tools do not adequately account for ENM
      uncertainties including varying functional forms, unique environmental behavior,
      economic costs, unknown supply and demand, and upstream emissions. The complexity
      of the ENM system necessitates a novel approach: in this study, the adaptation of
      an investment portfolio optimization model is demonstrated for optimization of
      ENM use in renewable energy technologies. Where a traditional investment
      portfolio optimization model maximizes return on investment through optimal
      selection of stock, ENM portfolio optimization maximizes the performance of
      energy technology systems by optimizing selective use of ENMs. Cumulative impacts
      of multiple ENM material portfolios are evaluated in two case studies: organic
      photovoltaic cells (OPVs) for renewable energy and lithium-ion batteries (LIBs)
      for electric vehicles. Results indicate ENM adoption is dependent on overall
      performance and variance of the material, resource use, environmental impact, and
      economic trade-offs. From a sustainability perspective, improved clean energy
      applications can help extend product lifespans, reduce fossil energy consumption,
      and substitute ENMs for scarce incumbent materials.

PMID- 29577722
TI  - 1,2,3- versus 1,2-Indeno Ring Fusions Influence Structure Property and Chirality
      of Corannulene Bowls.
AB  - Annulated corannulenes 3-5 form via distinct synthetic pathways: (i) Pd-catalyzed
      sp3 CH insertion, (ii) Pd-catalyzed aryl coupling, and (iii) silyl cation
      promoted C-F activation/CH insertion. Crystal structure, redox, and photophysical
      studies elucidate the differing influence of 1,2,3- versus 1,2-indeno ring
      fusions. Mono and dianions of 3-5 are characterized. Resolution of 4 gives
      enantiopure forms, allowing assessment of the bowl-inversion barrier.

PMID- 29577723
TI  - Arylketone pi-Conjugation Controls Enantioselectivity in Asymmetric Alkynylations
      Catalyzed by Centrochiral Ruthenium Complexes.
AB  - The origin of enantioselectivity in the asymmetric alkynylation of trihalomethyl
      ketones catalyzed by octahedral stereogenic-at-ruthenium complexes has been
      investigated through density functional theory calculations. Computational
      results support a mechanism involving formation of a ruthenium acetylide,
      followed by pre-coordination of the trihalomethyl ketone through the carbonyl
      oxygen and intramolecular attack of the acetylide via a compact four-membered
      transition state. Differences in computed free energies of activation for the
      formation of the major and minor propargyl alcohol enantiomers are in good
      agreement with the experimentally observed levels of asymmetric induction.
      Analysis of fragment distortion energies shows that disfavored transition states
      are destabilized due to the more severe distortion and loss of pi-conjugation in
      the coordinated arylketone fragments. Examination of the different substitution
      patterns in the ketone substrate and the catalyst reveals the key steric factors
      that control the enantioselectivity. Finally, calculations indicate promising
      directions for the simplification of the catalyst scaffold while preserving the
      high levels of enantioselectivity of these alkynylation reactions.

PMID- 29577724
TI  - Large Perpendicular Magnetocrystalline Anisotropy at the Fe/Pb(001) Interface.
AB  - The search for ultrathin magnetic films with large perpendicular
      magnetocrystalline anisotropy (PMA) has been inspired for years by the continuous
      miniaturization of magnetic units in spintronics devices. The common magnetic
      materials used in research and applications are based on Fe because the pure Fe
      metal is the best yet simple magnetic material from nature. Through systematic
      first-principles calculations, we explored the possibility to produce large PMA
      with ultrathin Fe on non-noble and non-magnetic Pb(001) substrate. Interestingly,
      huge magnetocrystalline anisotropy energy (MAE) of 7.6 meV was found in the
      Pb/Fe/Pb(001) sandwich structure with only half monolayer Fe. The analysis of
      electronic structures reveals that the magnetic proximity effect at the interface
      is responsible for this significant enhancement of MAE. The MAE further increases
      to 13.6 meV with triply repeated capping Pb and intermediate Fe layers.
      Furthermore, the MAE can be tuned conveniently by charge injection.

PMID- 29577726
TI  - Spiny Nanorod and Upconversion Nanoparticle Satellite Assemblies for
      Ultrasensitive Detection of Messenger RNA in Living Cells.
AB  - Quantitation and in situ monitoring of target mRNA (mRNA) in living cells remains
      a significant challenge for the chemical and biomedical communities. To
      quantitatively detect mRNA expression levels in living cells, we have developed
      DNA-driven gold nanorod coated platinum-upconversion nanoparticle satellite
      assemblies (termed Au NR@Pt-UCNP satellites) for intracellular thymidine kinase 1
      (TK1) mRNA analysis. The nanostructures were capable of recognizing target mRNA
      in a sequence-specific manner as luminescence of UCNPs was effectively quenched
      by Au NR@Pt within the assemblies. Following recognition, UCNPs detached from Au
      NR@Pt, resulting in luminescence restoration to achieve effective in situ imaging
      and quantifiable detection of target mRNA. The upconversional luminescence
      intensity of confocal images showed a good linear relationship with intracellular
      TK1 mRNA ranging from 1.17 to 65.21 fmol/10 MUg RNA and a limit of detection
      (LOD) of 0.67 fmol/10 MUg RNA. We believe that our present assay can be broadly
      applied for detection of endogenous biomolecules at the cellular and tissue
      levels and restoration of tissue homeostasis in vivo.

PMID- 29577725
TI  - Origins of the Mechanochemical Coupling of Peptide Bond Formation to Protein
      Synthesis.
AB  - Mechanical forces acting on the ribosome can alter the speed of protein
      synthesis, indicating that mechanochemistry can contribute to translation control
      of gene expression. The naturally occurring sources of these mechanical forces,
      the mechanism by which they are transmitted 10 nm to the ribosome's catalytic
      core, and how they influence peptide bond formation rates are largely unknown.
      Here, we identify a new source of mechanical force acting on the ribosome by
      using in situ experimental measurements of changes in nascent-chain extension in
      the exit tunnel in conjunction with all-atom and coarse-grained computer
      simulations. We demonstrate that when the number of residues composing a nascent
      chain increases, its unstructured segments outside the ribosome exit tunnel
      generate piconewtons of force that are fully transmitted to the ribosome's P
      site. The route of force transmission is shown to be through the nascent
      polypetide's backbone, not through the wall of the ribosome's exit tunnel.
      Utilizing quantum mechanical calculations we find that a consequence of such a
      pulling force is to decrease the transition state free energy barrier to peptide
      bond formation, indicating that the elongation of a nascent chain can accelerate
      translation. Since nascent protein segments can start out as largely unfolded
      structural ensembles, these results suggest a pulling force is present during
      protein synthesis that can modulate translation speed. The mechanism of force
      transmission we have identified and its consequences for peptide bond formation
      should be relevant regardless of the source of the pulling force.

PMID- 29577727
TI  - Pyrene-Containing ortho-Oligo(phenylene)ethynylene Foldamer as a Ratiometric
      Probe Based on Circularly Polarized Luminescence.
AB  - In this manuscript, we report the first synthesis of an organic monomolecular
      emitter, which behaves as a circularly polarized luminescence (CPL)-based
      ratiometric probe. The enantiopure helical ortho-oligo(phenylene)ethynylene ( o
      OPE) core has been prepared by a new and efficient macrocyclization reaction. The
      combination of such o-OPE helical skeleton and a pyrene couple leads to two
      different CPL emission features in a single structure whose ratio linearly
      responds to silver(I) concentration.

PMID- 29577728
TI  - High-Sensitivity Light Detection via Gate Tuning of Organometallic
      Perovskite/PCBM Bulk Heterojunctions on Ferroelectric Pb0.92La0.08Zr0.52Ti0.48O3
      Gated Graphene Field Effect Transistors.
AB  - Organometallic perovskite (OMP) CH3NH3PbI3 doped with [6,6]-phenyl-C61-butyric
      acid methyl ester (PCBM) has been shown to form bulk heterojunction (OMP-PCBM
      BHJ) for improved charge separation. In this work, the OMP-PCBM BHJ
      photosensitizer is combined with graphene field effect transistors (GFETs) with a
      ferroelectric Pb0.92La0.08Zr0.52Ti0.48O3 gate of high gating efficiency. A
      remarkable gate tunability via shifting the Fermi energy of graphene with respect
      to the valence band maximum and conduction band minimum of the OMP was observed,
      which is critical for facilitating efficient charge transfer across the OMP-PCBM
      BHJ/GFET interface. The combination of the high-efficiency charge separation by
      BHJ and charge transfer by high gate tunability leads to achievement of high
      photoresponsivity up to 7 * 106 A/W and detectivity exceeding 7 * 1012 Jones at
      550 nm at a small gate voltage of 1.0 V. These results represent almost 2 orders
      of magnitude improvement over that without a gate tuning under the similar
      experimental condition, illustrating the importance of the interface electronic
      structure in optimizing the optoelectronic performance of the OMP-PCBM BHJ/GFET
      devices.

PMID- 29577729
TI  - Toward Semistructural Cellulose Nanocomposites: The Need for Scalable Processing
      and Interface Tailoring.
AB  - Cellulose nanocomposites can be considered for semistructural load-bearing
      applications where modulus and strength requirements exceed 10 GPa and 100 MPa,
      respectively. Such properties are higher than for most neat polymers but typical
      for molded short glass fiber composites. The research challenge for polymer
      matrix biocomposites is to develop processing concepts that allow high cellulose
      nanofibril (CNF) content, nanostructural control in the form of well-dispersed
      CNF, the use of suitable polymer matrices, as well as molecular scale interface
      tailoring to address moisture effects. From a practical point of view, the
      processing concept needs to be scalable so that large-scale industrial processing
      is feasible. The vast majority of cellulose nanocomposite studies elaborate on
      materials with low nanocellulose content. An important reason is the challenge to
      prevent CNF agglomeration at high CNF content. Research activities are therefore
      needed on concepts with the potential for rapid processing with controlled
      nanostructure, including well-dispersed fibrils at high CNF content so that
      favorable properties are obtained. This perspective discusses processing
      strategies, agglomeration problems, opportunities, and effects from interface
      tailoring. Specifically, preformed CNF mats can be used to design nanostructured
      biocomposites with high CNF content. Because very few composite materials combine
      functional and structural properties, CNF materials are an exception in this
      sense. The suggested processing concept could include functional components
      (inorganic clays, carbon nanotubes, magnetic nanoparticles, among others). In
      functional three-phase systems, CNF networks are combined with functional
      components (nanoparticles or fibril coatings) together with a ductile polymer
      matrix. Such materials can have functional properties (optical, magnetic,
      electric, etc.) in combination with mechanical performance, and the comparably
      low cost of nanocellulose may facilitate the use of large nanocomposite
      structures in industrial applications.

PMID- 29577730
TI  - An Unprecedented (Semi)Favorskii Rearrangement. Evidence for the 2
      (Acyloxy)cyclopropanones.
AB  - Discovery and development of an unprecedented (semi)Favorskii rearrangement has
      been reported. The intermediacy of structurally singular (acyloxy)cyclopropanones
      has been unraveled by fruitful control experiments including a crossover
      experiment. This class of cyclopropanones is found to be inert for classical
      Favorskii functionalization and preferably undergoes a decycloisomerization (ring
      chain valence tautomerism) to alpha-(acyloxy)enones. A cascade conversion of
      alpha,alpha-diiodo-alpha'-acetoxyketones to (acyloxy)cyclopropanones via alpha
      iodo-alpha'-acetoxyketones has been achieved by the synchronous dual basicity
      (Lewis and Bronsted) of amines. The overall process is found to be very general
      for diverse substrates and highly efficient.

PMID- 29577731
TI  - Individually Dispersed Gold Nanoshell-Bearing Cellulose Nanocrystals with
      Tailorable Plasmon Resonance.
AB  - Cellulose nanocrystals (CNCs) can be attractive templates for the generation of
      functional inorganic/organic nanoparticles, given their fine sizes, aspect
      ratios, and sustainable worldwide availability in abundant quantities. Here, we
      present for the first time a scalable, surfactant-free, tailorable wet chemical
      process for converting commercially available CNCs into individual aspected gold
      nanoshell-bearing particles with tunable surface plasmon resonance bands. Using a
      rational cellulose functionalization approach, stable suspensions of positively
      charged CNCs have been generated. Continuous, conductive, nanocrystalline gold
      coatings were then applied to the individual, electrostatically stabilized CNCs
      via decoration with 1-3 nm diameter gold particles followed by electroless gold
      deposition. Optical analyses indicated that these core-shell nanoparticles
      exhibited two surface plasmon absorbance bands, with one located in the visible
      range (near 550 nm) and the other at near infrared (NIR) wavelengths. The NIR
      band possessed a peak maximum wavelength that could be tuned over a wide range
      (1000-1300 nm) by adjusting the gold coating thickness. The bandwidth and
      wavelength of the peak maximum of the NIR band were also sensitive to the
      particle size distribution and could be further refined by fractionation using
      viscosity gradient centrifugation.

PMID- 29577732
TI  - Factor Structure of the CVLT-II Short Form: Evidence From a Trauma-Exposed
      Sample.
AB  - The current study sought to investigate the factor structure of the California
      Verbal Learning Test-Second Edition (CVLT-II) Short Form in a trauma-exposed
      sample. We used confirmatory factor analysis to test four competing models
      proposed by Donders in a study investigating the CVLT-II Standard Form.
      Consistent with Donders, a four-factor model consisting of Attention Span,
      Learning Efficiency, Delayed Memory, and Inaccurate Memory was supported. These
      results confirm the latent structure of the CVLT-II holds for the CVLT-II in its
      Short Form as well as in a trauma-exposed sample. Findings are particularly
      important, given previous research indicating attention span and learning
      efficiency may underpin memory complaints in trauma-exposed individuals.

PMID- 29577733
TI  - Engaging Axiology: Enabling Meaningful Transdisciplinary Collaboration in Adapted
      Physical Activity.
AB  - In this article, I explore the concept of axiology in the context of adapted
      physical activity research and analyze its connection to the more commonly
      discussed paradigmatic assumptions of epistemology and ontology. Following
      methodological scholars, I argue for an acknowledgment of the pivotal role that
      axiology already plays in adapted physical activity research and for the
      potential interdisciplinary and transdisciplinary opportunities that could be
      enabled by engaging with axiology in more explicit ways. I discuss a number of
      potential axiological gaps between the field of adapted physical activity and
      disability communities, arguing that such differences may undermine attempts at
      doing meaningful transdisciplinary research with such communities. I offer
      strategies for bridging these axiological gaps, encouraging us to work together
      in axiologically reflexive ways in order to increase meaningful opportunities for
      more people with disabilities to be engaged in the movement-based activities and
      communities of their choice.

PMID- 29577734
TI  - Do clinicians assess patients' religiousness? An audit of an aged psychiatry
      community team.
AB  - OBJECTIVES: To determine the frequency and quality of religious history taking of
      patients by clinicians working in an old age psychiatry service. METHODS: A
      retrospective audit of 80 randomised patient files from the Koropiko Mental
      Health Services for Older People (MHSOP) in Middlemore Hospital, Auckland, New
      Zealand. RESULTS: A total of 66 clinical records were available for analysis. A
      religious history was taken in 33/66 (50%) patients. However, when such histories
      were evaluated using the FICA assessment tool, only 10/33 (30.3%) histories
      contained detailed information regarding the patient's religiousness.
      CONCLUSIONS: The infrequency and low quality of religious histories discovered in
      this audit suggest that clinicians need more training in taking a religious
      history from patients.

PMID- 29577737
TI  - Editorial.

PMID- 29577735
TI  - Evaluation of a Distance Learning Curriculum for Interprofessional Quality
      Improvement Leaders.
AB  - As health care systems move toward value-based care, training future leaders in
      quality improvement (QI) is essential. Web-based training allows for broad
      dissemination of QI knowledge to geographically distributed learners. The authors
      conducted a longitudinal evaluation of a structured, synchronous web-based,
      advanced QI curriculum that facilitated engagement and real-time feedback.
      Learners (n = 54) were satisfied (overall satisfaction; M = 3.31/4.00), and there
      were improvements in cognitive (immediate QI knowledge tests; P = .02), affective
      (self-efficacy of QI skills; P < .001), and skill-based learning (Quality
      Improvement Knowledge Application Tool; P < .001). There was significant
      improvement in affective transfer (interprofessional attitudes on the job; p <
      .01) but no significant change on cognitive (distal QI knowledge test; P = .91),
      or skill-based transfer (self-reported interprofessional collaboration job
      skills; P = .23). The findings suggest that this model can be effective to train
      geographically distributed future QI leaders.

PMID- 29577738
TI  - Challenged and changed: Quiet ego and posttraumatic growth in mothers raising
      children with autism spectrum disorder.
AB  - Posttraumatic growth theory posits that when life circumstances are perceived as
      stressful, secondary appraisal processes can be recruited in ways to facilitate
      both coping efforts and personal growth. Using a mixed-methods approach, we found
      mothers' most challenging experiences involved child behavior (e.g. aggression,
      communication, and social issues) and psychosocial impacts (e.g. lack of social
      support, perceived judgment of others, perceived loss, and personal distress).
      Descriptions of most rewarding experiences reflect posttraumatic growth
      frameworks including constructive perceptions about themselves, life, and their
      relationships as well as evidence for what Maercker and Zoellner call illusory
      types of posttraumatic growth. Quantitative data were subjected to a hierarchical
      regression analysis for self-reported posttraumatic growth and included mothers'
      demographics, child functioning, and psychosocial measures. As predicted,
      posttraumatic growth was positively associated with social support from mothers'
      most important network member and quiet ego characteristics, a type of eudaimonic
      motivation. Contrary to expectation, neither autism spectrum disorder-related
      rumination nor time since diagnosis (or their interaction) was associated with
      posttraumatic growth. Discussion focuses on the practical implications of our
      findings that posttraumatic growth-related coping includes both constructive and
      illusory forms and the importance of social support and eudaimonic motivation in
      facilitating positive forms of secondary coping.

PMID- 29577739
TI  - Choosing wisely and the use of antibiotics in ophthalmic surgery: There is more
      than meets the eye.
AB  - BACKGROUND:: One of the directions of modern ophthalmology is toward an
      odontoiatric model, and new settings of eye care are becoming the standard of
      care: one day surgery and also office-based therapies. METHODS:: Retrospective
      analysis of three tertiary-care centers in Italy and analysis of the literature.
      RESULTS:: We provide readers with state-of-the-art measures of prophylaxis in
      ophthalmic surgery. DISCUSSION AND CONCLUSION:: Role of antibiotics is criticized
      in the light of stewardship antimicrobial paradigm.

PMID- 29577740
TI  - Biological, Psychological, and Social Predictors of Longevity Among Utah
      Centenarians.
AB  - Studies of longevity among centenarians examine biological, psychological, and
      social factors, yet few consider these components concurrently. This study
      explores such factors individually and collectively, as they are related to days
      lived past the age of 100 years. Data from 268 family members of centenarians
      identified in the State of Utah between 2008 and 2015 were used in negative
      binomial models predicting number of days lived among the centenarians. Findings
      suggested that sleep latency (biological), life satisfaction (psychological), and
      attachment closeness (social) were predictive factors of more days lived within
      individual models. When considered together, sleep latency and life satisfaction
      remained significant predictors of days lived. Although biological factors are
      commonly considered in relation to longevity, this study further indicates that
      psychological and social factors may play important roles in life expectancy.
      Further examination is needed to explore how these factors link additionally to
      active life expectancy.

PMID- 29577742
TI  - Understanding Disability: Biopsychology, Biopolitics, and an In-Between-All
      Politics.
AB  - What do disability labels give us and what do they steal from us? How possible is
      it to live our lives without categories when life is necessarily categorical? In
      this brief provocation, I want to explore the disability labels through recourse
      to three perspectives that have much to say about categorization, disability, and
      the human condition: the biopsychological, the biopolitical, and, what I term, an
      in-between-all politics. It is my view that disability categories intervene in
      the world in some complex and often contradictory ways. One way of living with
      contradictions is to work across disciplinary boundaries, thus situating
      ourselves across divides and embracing uncertainty and contradiction to enhance
      all our lives. I will conclude with some interdisciplinary thoughts for the field
      of adapted physical activity.

PMID- 29577741
TI  - LIBERTI: A SMART study in plastic surgery.
AB  - BACKGROUND/AIMS: Laser treatment of burns scars is considered by some providers
      to be standard of care. However, there is little evidence-based research as to
      the true benefit. A number of factors hinder evaluation of the benefit of laser
      treatment. These include significant heterogeneity in patient response and
      possible delayed effects from the laser treatment. Moreover, laser treatments are
      often provided sequentially using different types of equipment and settings, so
      there are effectively a large number of overall treatment options that need to be
      compared. We propose a trial capable of coping with these issues and that also
      attempts to take advantage of the heterogeneous response in order to estimate
      optimal treatment plans personalized to each individual patient. It will be the
      first large-scale randomized trial to compare the effectiveness of laser
      treatments for burns scars and, to our knowledge, the very first example of the
      utility of a Sequential Multiple Assignment Randomized Trial in plastic surgery.
      METHODS: We propose using a Sequential Multiple Assignment Randomized Trial
      design to investigate the effect of various permutations of laser treatment on
      hypertrophic burn scars. We will compare and test hypotheses regarding laser
      treatment effects at a general population level. Simultaneously, we hope to use
      the data generated to discover possible beneficial personalized treatment plans,
      tailored to individual patient characteristics. RESULTS: We show that the
      proposed trial has good power to detect laser treatment effect at the overall
      population level, despite comparing a large number of treatment combinations. The
      trial will simultaneously provide high-quality data appropriate for estimating
      precision-medicine treatment rules. We detail population-level comparisons of
      interest and corresponding sample size calculations. We provide simulations to
      suggest the power of the trial to detect laser effect and also the possible
      benefits of personalization of laser treatment to individual characteristics.
      CONCLUSION: We propose, to our knowledge, the first use of a Sequential Multiple
      Assignment Randomized Trial in surgery. The trial is rigorously designed so that
      it is reasonably straightforward to implement and powered to answer general
      overall questions of interest. The trial is also designed to provide data that
      are suitable for the estimation of beneficial precision-medicine treatment rules
      that depend both on individual patient characteristics and on-going real-time
      patient response to treatment.

PMID- 29577743
TI  - Challenges, Opportunities, and Methods for Large-Scale Evaluations.
AB  - The logic, theory, and practice of large-scale evaluation were once limited to
      large federal initiatives. However, with the advent of regularly collected
      performance measures and the often multisite implementation of quality
      improvement efforts, there is an opportunity to adopt large-scale evaluation
      methods in local and regional evaluation efforts. While ineffective programs show
      little variation in their ineffectiveness, effective programs generally show a
      range of effects. A central task of large-scale evaluation is to describe and
      ascribe why the same program, implemented in multiple settings, produces
      different effects. By its attention to variation attributable to setting,
      activities, outputs, and by participants and documenting the conditions in which
      programs achieve greater and lesser success, large-scale evaluation supports the
      needs of decision-makers when choosing to implement an evidence-based program. In
      addition to knowing a program is effective, decision-makers want to know whether
      it is appropriate for their situation and what facilitates or impedes effective
      implementation and bears on the program's ultimate effectiveness. This article
      presents the different methods and approaches appropriate for effectively and
      efficiently constructing and executing a large-scale evaluation that will provide
      decision-makers the evidence they need for evidence-informed adoption of
      effective programs.

PMID- 29577744
TI  - Aromatic compounds produced by endophytic fungi isolated from red alga
      Asparagopsis taxiformis - Falkenbergia stage.
AB  - Endophytic fungi were isolated from red alga Asparagopsis taxiformis -
      Falkenbergia stage, collected from the Brazilian coast, and were identified as
      Annulohypoxylon stygium (AT-03) and A. yungensis (AT-06) based on their
      macro/micromorphological and molecular features. Bioassay-guided fractionation of
      the EtOAc extract from laboratory cultures of both strains yielded known
      compounds pyrogallol from A. stygium, (3R)-scytalone and (3R,4R)-4-hydroxy
      scytalone from A. yungensis. Pyrogallol was active against methicillin-resistant
      Staphylococcus aureus (MRSA) and Escherichia coli strains. An inactive fraction
      from A. stygium afforded two additional compounds, (3R,4R)-3,4,5-trihydroxy-1
      tetralone and tyrosol. Optically active compounds had their stereochemistry
      determined by circular dichroism (CD) spectroscopy.

PMID- 29577745
TI  - Cost Analysis of a High Support Housing Initiative for Persons with Severe Mental
      Illness and Long-Term Psychiatric Hospitalization.
AB  - OBJECTIVE: The objective of this article was to conduct a cost analysis comparing
      the costs of a supportive housing intervention to inpatient care for clients with
      severe mental illness who were designated alternative-level care while inpatient
      at the Centre for Addiction and Mental Health in Toronto. The intervention,
      called the High Support Housing Initiative, was implemented in 2013 through a
      collaboration between 15 agencies in the Toronto area. METHOD: The perspective of
      this cost analysis was that of the Ontario Ministry of Health and Long-Term Care.
      We compared the cost of inpatient mental health care to high-support housing.
      Cost data were derived from a variety of sources, including health administrative
      data, expenditures reported by housing providers, and document analysis. RESULTS:
      The High Support Housing Initiative was cost saving relative to inpatient care.
      The average cost savings per diem were between $140 and $160. This amounts to an
      annual cost savings of approximately $51,000 to $58,000. When tested through
      sensitivity analysis, the intervention remained cost saving in most scenarios;
      however, the result was highly sensitive to health system costs for clients of
      the High Support Housing Initiative program. CONCLUSIONS: This study suggests the
      High Support Housing Initiative is potentially cost saving relative to inpatient
      hospitalization at the Centre for Addiction and Mental Health.

PMID- 29577746
TI  - Comparative effects of some extraction solvents on the antimicrobial activity of
      Eucalyptus camaldulensis leaf, bud, capsule and seed crude extracts.
AB  - Well diffusion method was used to evaluate the antibacterial activity of
      Eucalyptus camaldulensis, while the antifungal effect was assessed by calculating
      the reduction percent in the radial growth of mycelia. The inhibition zones
      exerted by E. camaldulensis crude extracts varied significantly (p <= 0.01). The
      capsule crude extract (acetone 30%) highly inhibited the growth of Acinetobacter
      baumannii (35 mm clear zone). The highest antifungal activity was against
      Rhizopus stolonifer with a reduction percent in its radial growth reached to 96%.
      The bacterial MICs ranged from 20 to 0.5 mg/mL against Escherichia coli and
      Bacillus subtilis respectively. The MIC values for fungi were between 18 mg/mL
      (Mucor sp.) and 4 mg/mL (R. stolonifer). Both type and concentration of the
      solvent greatly affected the antimicrobial potentials of E. camaldulensis. The
      empty capsule and bud of E. camaldulensis are recognized for the first time as
      potentially natural resources of effective antimicrobial agents.

PMID- 29577747
TI  - Fractures of the Lateral Process of the Talus With Associated Ankle Instability:
      A Report of 2 Cases.
AB  - : Fractures of the lateral process of the talus are uncommon, but often
      overlooked. They can result in significant functional deficit with residual
      nonunion and arthritis if not recognized and treated appropriately. We describe 2
      cases of such injuries, one with acute recognition and management, and one with
      delayed diagnosis and nonunion. In both cases, pain from the fracture was
      accompanied by symptoms of instability requiring simultaneous lateral ligament
      reconstruction along with fracture fixation. Evaluation of patients with lateral
      process fractures should include assessment of the lateral ligaments; ankle
      instability may need to be surgically addressed along with intervention for
      fracture fixation. LEVELS OF EVIDENCE: Level IV: Case report.

PMID- 29577748
TI  - Incarcerated Plantar Dislocation of the First Metatarsophalangeal Joint:
      Reduction Using Intra-articular Saline Injection.
AB  - : Plantar dislocation of the first metatarsophalangeal (MTP) joint is exceedingly
      rare, and in prior reported cases, simple closed manipulation easily enabled
      reduction. We present here the first reported plantar dislocation that failed
      closed manipulation. We also report a technique involving injection of saline
      into the joint to facilitate reduction. The saline insufflation likely relieves
      buttonholing of the metatarsal head through the dorsal joint capsule. For first
      MTP joint plantar dislocations that fail reduction with manipulation, we
      recommend attempting injection of the joint with saline prior to subjecting the
      patient to open reduction. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case
      report.

PMID- 29577749
TI  - Proliferation, Migration, and ECM Formation Potential of Human Annulus Fibrosus
      Cells Is Independent of Degeneration Status.
AB  - Objective The objective was to evaluate the proliferating, migratory and
      extracellular matrix (ECM) forming potential of annulus fibrosus cells derived
      from early (edAFC) or advanced (adAFC) degenerative tissue and their usability as
      a possible cell source for regenerative approaches for AF closure. Design EdAFC (
      n = 5 Pfirrman score of 2-3) and adAFC (n = 5 Pfirrman score of 4-5) were
      isolated from tissue of patients undergoing spine stabilizing surgery. Cell
      migration on stimulation with human serum (HS), platelet-rich plasma (PRP), and
      transforming growth factor beta-3 (TGFB3) was assessed by migration assay and
      proliferation was assessed on stimulation with HS. Induction of ECM synthesis was
      evaluated by gene expression analysis of AF-related genes in three-dimensional
      scaffold cultures that have been stimulated with 5% PRP or 10 ng/mL TGFB3 and
      histologically by collagen type I, type II, alcian blue, and safranin-O staining.
      Results EdAFC and adAFC were significantly attracted by 10% HS and 5% PRP.
      Additionally, both cell groups proliferated under stimulation with HS.
      Stimulation with 10 ng/mL TGFB3 showed significant induction of gene expression
      of collagen type II and aggrecan, while 5% PRP decreased the expression of
      collagen type I. Both cell groups showed formation of AF-like ECM after
      stimulation with TGFB3, whereas stimulation with PRP did not. Conclusions Our
      study demonstrated that AF cells retain their potential for proliferation,
      migration, and ECM formation independent of the degeneration status of the
      tissue. Proliferation, migration, and ECM synthesis of the endogenous AF cells
      can be supported by different supplements. Hence, endogenous AF cells might be a
      suitable cell source for a regenerative repair approaches.

PMID- 29577750
TI  - A new furostanol saponin from Dendrobium chrysanthum Lindl. with cytotoxic
      activity.
AB  - A new furostanol saponin, (25R)-26-O-(alpha-d-glucopyranosyl)-(1->2)-alpha-l
      rhamnopyranosyl-furost-5-ene-3beta, 22alpha, 26-triol-3-O-alpha-d-glucopyranoside
      (1), together with four known compounds 2-5 were isolated from the ethanolic
      extract of the stems of Dendrobium chrysanthum Lindl. The structures of these new
      compounds were identified by extensive spectroscopic analysis including 1D and 2D
      NMR and HR-ESI-MS, as well as chemical methods. Compounds 1-3 were isolated from
      D. chrysanthum for the first time. Furthermore, the inhibitory effects of the
      compounds on tumor cells were evaluated, and compounds 1-2 exhibited significant
      cytotoxic activities potentially against SPC-A1, MCF-7 and HeLa human cancer cell
      lines. Compounds 3-5 showed inhibitory activity against the SPC-A1 and MCF-7.

PMID- 29577751
TI  - New compound from Euphorbia alatavica Boiss.
AB  - One new compound alatavinol (1), together with five known compounds, kaempferol
      (2), quercetin (3), laricircsinol (4), secoisolariciresinol (5) and loliolide (6)
      were isolated from the whole plant of Euphorbia alatavica Boiss. Those compounds
      were isolated and purified by various column chromatographic methods and their
      structures were elucidated by spectroscopic (1D, 2D NMR, and HR-MS) chemical
      analyses. All compounds were isolated for the first time from E. alatavica Boiss,
      and biochemical pathway of the new compound has been hypothesized. Furthermore,
      these compounds were evaluated for antioxidant properties based on the DPPH
      radical scavenging activities. Results showed that IC50 values of compounds 1, 3,
      4, 5 and 6 were 25.69, 1.88, 2.87, 11.55 and 17.81 MUg/mL, respectively, as
      compared to the control ascorbic acid (5.34 MUg/mL).

PMID- 29577752
TI  - Fungal burden exposure assessment in podiatry clinics from Ireland.
AB  - : Fungi are amongst the bioaerosols of most importance, as indicated by the
      growing interest in this field of research. The aim was to characterize the
      exposure to fungal burden in podiatry clinics using culture-based and molecular
      methods. METHODS: Airborne fungi were collected using an impaction air sampler
      and surface samples were also performed. Fourteen air samples were collected for
      direct detection of fungal DNA from filamentous fungi and dermatophytes. Overall,
      63.6 % of the evening samples and 46 % of the morning samples surpassed the
      threshold values (150 CFU/m3). Molecular detection, by real time PCR, of the
      target fungal species/strains (Aspergillus and Stachybotrys species) was negative
      for all samples collected. Trichophyton rubrum was detected by PCR analysis in
      one DNA sample collected on day six. Results suggest the use of both culture
      based and molecular methodologies are desirable for a complete evaluation of
      fungal burden in this particular health care setting.

PMID- 29577753
TI  - Purification of the total steroidal saponins from fenugreek seeds (Trigonella
      foenum-graecum L.) using aqueous two-phase system and determination of diosgenin
      content using micellar electrokinetic chromatography method.
AB  - The total steroidal saponins, particularly its major steroidal sapogenin
      (diosgenin), are the main active principles of fenugreek seed extract. In this
      study, an ethanol-salt aqueous two-phase system (ATPS) was explored for the
      purification of the total steroidal saponins, and the process conditions were
      optimized by response surface methodology (RSM). Under the optimized conditions,
      the RSM predicted recovery of the total steroidal saponins in the top phase of
      ATPS was 97.9%, which agreed with the average experimental recovery (98.3 +/-
      4.2% (n = 6)). Moreover, a rapid micellar electrokinetic chromatography (MEKC)
      method was developed for the determination of diosgenin from extracts. The
      diosgenin content in the ATPS top phase extract was 3-fold higher than that in
      crude extract, suggesting this ATPS having a great potential for purification
      pharmacological active ingredients from fenugreek seeds.

PMID- 29577754
TI  - A Multivariate Analysis of the Pathological Narcissism Inventory's Nomological
      Network.
AB  - The Pathological Narcissism Inventory (PNI) has enjoyed widespread use in the
      study of the narcissism. However, questions have been raised about whether the
      PNI's grandiosity scale adequately captures narcissistic grandiosity as well as
      other popular measures do. Specifically, some have noted that PNI grandiosity
      shows a pattern of external associations that diverges from patterns for
      narcissistic grandiosity predicted by experts, and is more similar to the
      predictions for the vulnerability scale than is desirable. Previous research
      driving these critiques has relied on patterns of zero-order correlations to
      examine the nomological networks of these scales. The present study reexamines
      the nomological networks of PNI grandiosity and vulnerability scales using
      hierarchical regression. Results indicate that once accounting for overlapping
      variance of vulnerability and grandiosity, the unique variance in the PNI's
      grandiosity scale closely matches contemporary expert conceptualizations of
      narcissistic grandiosity based on expected associations with other personality
      variables.

PMID- 29577755
TI  - Mono- and di-thiocarbamate inhibition studies of the delta-carbonic anhydrase
      TweCAdelta from the marine diatom Thalassiosira weissflogii.
AB  - The inhibition of the delta-class carbonic anhydrase (CAs, EC 4.2.1.1) from the
      diatom Thalassiosira weissflogii, TweCAdelta, was investigated using a panel of
      36 mono- and di-thiocarbamates chemotypes that have recently been shown to
      inhibit mammalian and pathogenic CAs belonging to the alpha- and beta-classes.
      TweCAdelta was not significantly inhibited by most of such compounds (KI values
      above 20 uM). However, some aliphatic, heterocyclic, and aromatic mono and di
      thiocarbamates inhibited TweCAdelta in the low micromolar range. For some
      compounds incorporating the piperazine ring, TweCAdelta was effectively inhibited
      (KIs from 129 to 791 nM). The most effective inhibitors identified in this study
      were 3,4-dimethoxyphenyl-ethyl-mono-thiocarbamate (KI of 67.7 nM) and the R
      enantiomer of the nipecotic acid di-thiocarbamate (KI of 93.6 nM). Given that the
      activity and inhibition of this class of enzyme have received limited attention
      until now, this study provides new molecular probes and information for
      investigating the role of delta-CAs in the carbon fixation processes in diatoms,
      which are responsible for significant amounts of CO2 taken from the atmosphere by
      these marine organisms.

PMID- 29577756
TI  - Identification of cisplatin-binding sites on the large cytoplasmic loop of the
      Na+/K+-ATPase.
AB  - Cisplatin is the most widely used chemotherapeutic drug for the treatment of
      various types of cancer; however, its administration brings also numerous side
      effects. It was demonstrated that cisplatin can inhibit the Na+/K+-ATPase (NKA),
      which can explain a large part of the adverse effects. In this study, we have
      identified five cysteinyl residues (C452, C456, C457, C577, and C656) as the
      cisplatin binding sites on the cytoplasmic loop connecting transmembrane helices
      4 and 5 (C45), using site-directed mutagenesis and mass spectrometry experiments.
      The identified residues are known to be susceptible to glutathionylation
      indicating their involvement in a common regulatory mechanism.

PMID- 29577757
TI  - Association between sperm mitochondrial ND2 gene variants and total fertilization
      failure.
AB  - : The objective of this study was to explore the association of sperm
      mitochondrial ND2 (MT-ND2) gene variants with total fertilization failure (TFF).
      A retrospective comparative study of 246 cases of fresh in vitro fertilization
      (IVF) cycles or half-intracytoplasmic sperm injection cycles in the Han Chinese
      population was performed from July 2011 to May 2017. A total of 59 cases
      undergoing TFF, and 187 control cases with normal fertilization (fertilization
      rates >50%) were included. The sperm mitochondrial genovariation was determined
      using nested sequencing. A total of 32 homoplasmic variants and 47 heteroplasmic
      variants of MT-ND2 gene were observed in this study. There were no significant
      differences in the frequencies of the 32 homoplasmic variants of MT-ND2 gene
      between the TFF and control groups. A total of 53 pair-wise comparisons were
      performed, and the general characteristics of the IVF failure and control
      subjects were adjusted in logistic models. Data suggested that there were no
      significant differences in the frequencies of point 4914, 5320, and 5426
      heteroplasmic variants of MT-ND2 gene between the TFF and control groups. In
      addition, no significant difference was observed in the frequency of mtDNA
      haplogroup D or haplogroup G between the IVF failure group and the normal
      fertilization group. This study suggests that the MT-ND2 gene variants might not
      be associated with TFF. ABBREVIATIONS: ATP: adenosine triphosphate; dNTP: deoxy
      ribonucleoside triphosphate; FADH2: flavin adenine dinucleotide; FDR: false
      discovery rate; FSH: follicle-stimulating hormone; IVF: in vitro fertilization;
      LH: luteinizing hormone; MTATP6: mitochondrially encoded ATP synthase 6; MTCYB:
      mitochondrially encoded cytochrome b; mtDNA: mitochondrial DNA; MT-ND2:
      mitochondrial ND2; NADH: nicotinamide adenine dinucleotide; ND2: NADH
      dehydrogenase subunit 2; OXPHOS: oxidative phosphorylation; PCR: single
      nucleotide polymorphisms; SNPs: single nucleotide polymorphisms; TFF: total
      fertilization failure.

PMID- 29577758
TI  - Petroleum coke exposure leads to altered secretome profiles in human lung models.
AB  - Petroleum coke (PC) is a coal-like product that is produced during the refinement
      of crude oil and bituminous sand. Fugitive dust from open storage of PC in urban
      areas is a potential human health concern. Animal inhalation studies suggest that
      PC leads to an adverse pulmonary histopathology, including areas of fibrosis and
      chronic inflammation; however, little is known about its impact on human health.
      In order to identify biomarkers and cellular pathways that are associated with
      exposure, we performed two-dimensional liquid chromatography-mass spectrometric
      analyses on secreted proteins from two human lung culture models. A total of 2795
      proteins were identified and relatively quantified from an immortalized cell line
      and 2406 proteins from primary cultures that were either mock treated or exposed
      to particulate matter with a diameter of 2.5-10 MUm PC or filtered urban air
      particulates for 16 h. Pathway analysis on secretomes from primary lung cultures
      indicated that PC exposure suppressed the secretion of proteins involved in the
      organization of the extracellular matrix and epithelial differentiation. Because
      these cellular processes could facilitate fibrosis, we performed chronic 12-day
      exposure studies on three-dimensional human lung cultures consisting of epithelia
      and stromal fibroblasts. Relative to mock-treated cells, matrix metallopeptidase
      9 levels in the conditioned media were lower by 4 days postexposure and remained
      suppressed for the duration of the experiment. Immunocytochemical staining of
      collagen III, a marker associated with fibrosis, showed increased accumulation in
      the epithelial layer and at the air-liquid interface.

PMID- 29577759
TI  - [Seroprevalence of Bordetella pertussis antibodies in adults in Hungary: results
      of an epidemiological cross-sectional study].
AB  - INTRODUCTION: Pertussis (whooping cough) is an acute respiratory tract infection
      caused by Bordetella pertussis that is characterized by a chronic, severe cough.
      The optimum immunization schedule for pertussis is unclear, so these vary by
      countries. AIM: To estimate the seroprevalence of pertussis in adults in Hungary.
      METHOD: Serum anti-pertussis toxin immunoglobulin G (anti-PT IgG) antibody levels
      were analyzed using enzyme-linked immunosorbent assay in adults in general
      practitioners' practices during one year. Sera were classified following
      manufacturer's instructions as: strongly indicative of current/recent infection
      (>=1.5 optical density [OD] units); indicative of current/recent infection (>=1.0
      OD units); seropositive (>0.3 OD units); or seronegative (<=0.3 OD units).
      RESULTS: 1999 adults (60.6% female; mean age 47.4 +/- 17.7 years) were included.
      14.8% were seropositive, 1.1% were indicative of current/recent infection, and
      0.1% were strongly indicative of current/recent infection. CONCLUSIONS: 85.2% of
      the subjects were seronegative and therefore susceptible to pertussis infection.
      Approximately 1% was suspicious of current/recent pertussis infection,
      potentially transmissible to susceptible young infants. Vaccination of adults is
      a key way to indirectly protect infants. Orv Hetil. 2018; 159(13): 503-510.

PMID- 29577761
TI  - [Open and endovascular repair of iliac artery aneurysms].
AB  - INTRODUCTION AND AIM: Iliac artery aneurysms make up 2% of all aneurysms. There
      are only a few data available on the results of surgical treatment, therefore the
      optimal treatment is unclear. Our objective was the retrospective analysis of the
      perioperative morbidity and mortality of patients who underwent iliac artery
      surgery as well as the comparison of elective open surgery and endovascular iliac
      aneurysm repair (EVIAR). METHOD: Retrospective analysis of patients who underwent
      surgery for iliac artery aneurysm between 1 January 2005 and 31 December 2014.
      RESULTS: During the 10-year period, 62 patients with a mean age of 68.9 years
      underwent elective surgery for iliac artery aneurysm (54 males, 87.1%). In 10
      cases acute surgery was performed due to aneurysm ruptures (13.9%), 3 patients
      died within the perioperative period (30%). Regarding anatomical localisation,
      aneurysm developed mostly on the common iliac artery (80.6%). As an elective
      surgery, 35 patients (56.5%) underwent open surgery, 25 (40.3%) underwent EVIAR
      and other endovascular interventions were performed in 2 cases (3.2%).
      Postoperative complications (1 patient [4.0%] vs. 17 patients [48.5%]; p<0.001)
      and intensive care treatment (29 patients [82.8%] vs. 2 patients [8.0%]; p<0.001)
      were significantly rarer after EVIAR than after open surgery. Furthermore, EVIAR
      resulted in considerably shorter postoperative hospital stays (4.7 +/- 2.3 days
      vs. 11.8 +/- 12.2 days; p = 0.006) and significantly less blood transfusion
      demand (1 patient [4.0%] vs. 26 patients [74.2%]; p<0.001). There were no
      significant differences regarding long-term survival rates between EVIAR and open
      surgery (81.4% vs. 71.4%; p = 0.95). CONCLUSION: In case of the surgical
      treatment of iliac artery aneurysms, owing to the lower complication rates and
      shorter postoperative length of stay, EVIAR is primarily recommended. Orv Hetil.
      2018; 159(13): 520-525.

PMID- 29577762
TI  - [Oral mucositis as the most common complication of childhood cancer therapy.
      Review of the literature].
AB  - Mucositis is the most common oral complication of cancer therapy. Oral mucositis
      in childhood is more frequent and severe compared to adults, especially in
      children with leukemia. Lesions develop as the chemotherapeutic agents attack the
      rapidly dividing cells of the oral mucous membrane. Patients may experience
      trouble in eating, drinking, swallowing or even speaking due to the significant
      pain caused by the ulceration of the oral mucosa. Oral mucositis has a direct
      impact on the quality of life and may affect survival. The regular assessment of
      the oral mucosa is crucial during chemotherapy to evaluate the effectiveness of
      the oral mucositis prevention and treatment. Several oral mucositis scoring tools
      have been developed for adults to qualify the symptoms, but there is no
      universally accepted assessment scale for children. The prevention and treatment
      of therapy-related mucositis is difficult, though several methods and
      pharmacologic agents have been tested. Here we discuss the pathogenesis of
      chemotherapy-induced oral mucositis, the available assessment tools and their
      applicability to pediatric patients and the available therapeutic and preventive
      strategies. Orv Hetil. 2018; 159(13): 495-502.

PMID- 29577763
TI  - [An objective scoring system to evaluate the credibility of health related
      websites].
AB  - INTRODUCTION AND AIM: The unreliable quality of online health contents poses a
      serious challenge to the medical profession. Evaluating websites on the basis of
      their credibility increases the chance for readers to access professional content
      of better quality. Hungary still lags behind in taking practical steps to improve
      the quality and reliability of online patient education. METHOD: EgeszsegKommando
      (HealthCommando) is a new Hungarian objective scoring system established to
      evaluate the credibility of health related websites. It uses four types of
      indicators: transparency, content, recommendations, references. RESULTS: We
      evaluated 122 websites with EgeszsegKommando. Out of this, 22.1% qualified as
      credible. The same assessment using JAMA benchmarks yielded only one credible
      website (0.8%). The most frequent deficiencies were the absence of reference to
      source, the omission of the quote that "the website information does not replace
      the doctor-patient discussion", and the identity of the author. In 45.9% of the
      cases, however, the content was written by medical professionals with contact
      information. CONCLUSION: By applying different types of credibility and quality
      indicators in a scoring system, EgeszsegKommando can efficiently assess the
      websites on health-awareness. In cases where the recognized indicators are absent
      multiple times from a website, it will not pass the credibility test. Thus,
      EgeszegKommando can act as a filter. At the same time, EgeszsegKommando is also
      capable of assessing webpages of different sorts systemically, and can recommend
      a proportionately large amount of reliable Hungarian medical web resources to
      those interested. Orv Hetil. 2018; 159(13): 511-519.

PMID- 29577764
TI  - [Immunoadsorption in a patient with dilated cardiomyopathy. The first case in
      Hungary].
AB  - Dilated cardiomyopathy is the main cause of heart transplantation. The etiology
      is unknown in almost half of the cases. Many cardiac specific antibodies have
      been identified till now which can cause decreased cardiac function, ventricular
      tachycardia or sudden heart death. The prognosis of DCM is poor despite the
      development of medical treatment. Immunoadsorption is hopeful since, with the
      removal of antibodies, cardiac function and NYHA class can improve and LVAD/heart
      transplantation-free survival can be prolonged. At the University of Debrecen,
      Faculty of Medicine, Department of Internal Medicine, Division of Angiology,
      Intensive Care and Therapeutic Apheresis Unit we performed the first
      immunoadsorption. Our patient was a 43-year-old man with idiopathic dilated
      cardiomyopathy, NYHA class IV, a heart transplantation candidate, whose cardiac
      specific antibody, type IgG was indentified by Western blot. Before the treatment
      he had ejection fraction of 18%. Discussing with his cardiologists we decided for
      immunoadsorption therapy. We performed 5 cycles on consecutive days in Intensive
      Care Unit. After 1 month we detected improvement in exercise capacity. We
      detected improvement in isovolemic contraction (from 465 mmHg/s to 575 mmHg/s),
      increased stroke volume (from 49 ml to 66 ml). After 3 months we repeated SPECT
      investigation which showed improvement in ejection fraction, from 18% to 32%. Orv
      Hetil. 2018; 159(13): 532-536.

PMID- 29577765
TI  - Incidence of Drug Interactions Identified by Clinical Pharmacists in Veterans
      Initiating Treatment for Chronic Hepatitis C Infection.
AB  - BACKGROUND: Many direct-acting antivirals (DAAs) have drug-drug interactions
      (DDIs) with the potential to affect efficacy and safety. OBJECTIVE: To describe
      the incidence and severity of DDIs with DAAs identified by the hepatitis C virus
      (HCV) clinical pharmacist within a Veterans Affairs health care system. METHODS:
      This single-center, retrospective cohort study evaluated patients with HCV
      treated with DAA therapy. Primary end points included the total number of
      identified DDIs, percentage of patients with at least 1 DDI, mean number of DDIs
      per patient, and the number of DDIs by severity category. Additional end points
      included characterization of interacting drugs, clinical consequence of
      interaction, intervention recommended, acceptance rate of actionable
      recommendations, and achievement of sustained virological response 12 weeks after
      treatment (SVR12). RESULTS: A total of 300 patients were included. There were 554
      identified DDIs, and 80.3% of patients had at least 1 DDI, with an average of
      1.85 DDIs per patient; 76% of the DDIs identified were categorized as either a
      potentially clinically significant or critical interaction. The most common DDIs
      involved acid suppression agents (20%). Patient monitoring was the most commonly
      recommended intervention (59%), followed by dose modification of the interacting
      medication (30%). There was no difference in SVR12 between patients with at least
      1 DDI compared with those with no DDIs (94.8% vs 95.8%; P = 0.73). There were a
      total of 227 actionable recommendations, with an acceptance rate of 84.1%.
      CONCLUSIONS: This study suggests that DDIs are prevalent among patients treated
      with DAAs for HCV. A HCV clinical pharmacist can help optimize patient care by
      identifying DDIs and recommending interventions to providers.

PMID- 29577766
TI  - Cost of Prescription Drug-Related Morbidity and Mortality.
AB  - BACKGROUND: Public attention and recent US Congressional activity has intensified
      focus on escalating medication prices. However, the actual cost of medication use
      extends beyond the up-front cost of purchasing medicines. It also encompasses the
      additional medical costs of morbidity and mortality resulting from nonoptimized
      medication regimens, including medication nonadherence. OBJECTIVES: Applying the
      most current nationally representative data sources, our goal was to estimate the
      cost of prescription drug-related morbidity and mortality in the United States.
      METHODS: Total costs of nonoptimized prescription drug use and average pathway
      costs for a patient who experienced a treatment failure (TF), a new medical
      problem (NMP), or a TF and NMP were modeled in Microsoft Excel (Microsoft
      Corporation, Redmond, WA) and TreeAge Pro Healthcare, v2014 (TreeAge Software,
      Inc, Williamstown, MA), respectively. RESULTS: The estimated annual cost of
      prescription drug-related morbidity and mortality resulting from nonoptimized
      medication therapy was $528.4 billion in 2016 US dollars, with a plausible range
      of $495.3 billion to $672.7 billion. The average cost of an individual
      experiencing TF, NMP, or TF and NMP after initial prescription use were $2481
      (range: $2233, $2742), $2610 (range: $2374, $2848) and $2572 (range: $2408,
      $2751), respectively. CONCLUSIONS: The estimated annual cost of drug-related
      morbidity and mortality resulting from nonoptimized medication therapy was $528.4
      billion, equivalent to 16% of total US health care expenditures in 2016. We
      propose expansion of comprehensive medication management programs by clinical
      pharmacists in collaborative practices with physicians and other prescribers as
      an effective and scalable approach to mitigate these avoidable costs and improve
      patient outcomes.

PMID- 29577767
TI  - Reply: Should an LDL Cholesterol Target-Based Approach Be Readopted?

PMID- 29577768
TI  - Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing
      Percutaneous Coronary Intervention: Where Are We Now?
AB  - OBJECTIVE: To synthesize the literature and provide guidance to practitioners
      regarding double therapy (DT) and triple therapy (TT) in patients with atrial
      fibrillation (AF) requiring percutaneous coronary intervention (PCI). DATA
      SOURCES: PubMed and MEDLINE (January 2000 to February 2018) were searched using
      the following terms: atrial fibrillation, myocardial infarction, acute coronary
      syndrome, percutaneous coronary intervention, anticoagulation, dual-antiplatelet
      therapy, clopidogrel, aspirin, ticagrelor, prasugrel, and triple therapy. STUDY
      SELECTION AND DATA EXTRACTION: The results included randomized and nonrandomized
      clinical trials and meta-analyses. Each study was reported based on study design,
      population, intervention, comparator, and key cardiovascular (CV) and bleeding
      outcomes. DATA SYNTHESIS: A total of 15 studies were included in the review. The
      majority of studies evaluating DT and TT utilized clopidogrel and warfarin as
      components of the regimen, although there are emerging data with newer agents.
      Evidence purporting DT regimens to be equally effective in preventing CV events
      and improved safety profiles compared with TT regimens included populations with
      relatively low risk for recurrent CV events, and many of these studies were
      observational in nature. Overall, current evidence as well as American and
      European guidelines support the use of TT in patients with AF who require PCI for
      the least possible amount of time, depending on patient-specific factors
      involving bleeding and thrombosis. CONCLUSIONS: In the majority of patients with
      AF who require PCI, TT should be used for the shortest period of time possible.
      DT regimens may be used in patients requiring PCI who have low risk for
      thrombosis and/or high bleeding risk.

PMID- 29577769
TI  - Perceptions of Healthy Eating Among Hispanic Parent-Child Dyads.
AB  - Limited research exists exploring the perceptions of healthy and unhealthy eating
      among Hispanic families, yet understanding their perceptions could inform public
      health practice with regard to nutrition and obesity prevention. This study
      conducted an exploratory analysis of interview data collected from 25 parent
      child dyads as part of a program evaluation to learn more about both parent and
      child beliefs and practices regarding healthy eating, and in particular fruit and
      vegetable consumption. Families described an incomplete knowledge regarding
      healthy eating, specifically how to increase fruit and vegetable consumption, and
      the benefits of healthy eating as well as risks of unhealthy eating. Parents in
      particular seemed to identify many of the foods to avoid but were unclear about
      healthier alternatives. Children focused more on the benefits of healthy eating,
      while parents spoke more about the risks of unhealthy eating and the challenges
      of eating vegetables, particularly among families where child weight was also
      raised as a concern.

PMID- 29577770
TI  - Enrolling Underserved Women in mHealth Programs: Results From Text4baby Outreach
      Campaigns.
AB  - Public health practitioners have increasingly leveraged technology-based
      communication to get health information into the hands of hard-to-reach
      populations; however, best practices for outreach and enrollment into mobile
      health (mHealth) programs are lacking. This article describes enrollment results
      from campaigns focused on enrolling underserved pregnant women and mothers in
      Text4baby-a free, mHealth service-to inform outreach strategies for mHealth
      programs. Text4baby participants receive health and safety information,
      interactive surveys, alerts, and appointment reminders through at least three
      weekly texts and a free app-timed to users' due date or babies' birth date.
      Text4baby worked with partners to implement national, state, and community-based
      enrollment campaigns. Descriptive statistics were used to compare baseline
      enrollment prior to a campaign with enrollment during a campaign to generate
      enrollment estimates. Enrollment rates were calculated for campaigns for which
      the number targeted/reached was available. National television campaigns resulted
      in more than 10,000 estimated enrollments. Campaigns that were integrated with an
      existing program and text-based recruitment had the highest enrollment rates,
      ranging from 7% to 24%. Facebook advertisements and traditional media targeting
      providers and consumers were least effective. mHealth programs should consider
      text-based recruitment and outreach via existing programs; additional research is
      needed on return on investment for different outreach strategies and on the
      effectiveness of different outreach strategies at reaching and enrolling specific
      target populations.

PMID- 29577772
TI  - Training Community Health Workers in Motivational Interviewing to Promote Cancer
      Screening.
AB  - Health disparities researchers attempting to engage and effectively deliver
      interventions to underserved populations often encounter a number of challenges
      ranging from geographical considerations to more complex issues of medical
      mistrust. While there are a number of strategies researchers may employ to
      address these challenges, one of the most successful of these has been the use of
      community health workers (CHWs). Despite the documented success of CHWs, little
      information exists on the use of theory-driven intervention strategies with these
      community partners. Researchers who have partnered with CHWs tend to provide
      brief descriptions of training strategies and provide little discussion of the
      challenges and barriers to training a lay population in the delivery of technical
      interventions, including ensuring fidelity to the intervention protocol. The
      purpose of this article is to describe the feasibility of training CHWs to
      deliver a motivational interviewing intervention to promote cancer screening in
      underserved populations. With this article we present an innovative way to use
      motivational interviewing delivered by CHWs. Specifically, we will detail the
      development of the training protocol, the implementation of that training in a
      variety of research settings, and the development and implementation of fidelity
      protocols. We will use examples from two research studies where CHWs were
      successfully trained to use MI to promote cancer screening in underserved
      communities to highlight the challenges and barriers faced in developing and
      implementing the training and strategies used to overcome these challenges during
      the refinement of the intervention.

PMID- 29577771
TI  - A Participatory Process to Engage Appalachian Youth in Reducing Sugar-Sweetened
      Beverage Consumption.
AB  - Children and adolescents consume excessive amounts of sugar-sweetened beverages
      (SSBs), which are associated with adverse health outcomes. We describe a yearlong
      participatory research study to reduce SSBs in Central Appalachia, where
      excessive consumption is particularly prevalent. This study was conducted in
      partnership with a community advisory board in Southwest Virginia. Nine "youth
      ambassadors," aged 10 to 13 years helped to systematically adapt SIPsmartER, an
      effective theory-based program for Appalachian adults, to be age and culturally
      appropriate and meet desired theoretical objectives. They then assisted with
      delivering the curriculum during a school-based feasibility study and led an
      advocacy event in their community. Satisfaction surveys and feedback sessions
      indicate that ambassadors found the program acceptable and important for other
      students. Validated surveys and focus groups suggested that theoretical
      objectives were met. Findings from these mixed methods sources informed
      curricular changes to further enhance acceptability and refine theoretical
      objectives. Participation in follow-up advocacy activities was tracked and
      described. Following the yearlong study, ambassadors reported having advocacy
      skills and motivation to continue reducing SSB intake in their community.
      Results, challenges, and lessons learned are presented to inform larger efforts
      to enhance acceptability of programs and inspire youth to take action to reduce
      health disparities in Appalachian communities.

PMID- 29577773
TI  - The promise of eHealth for primary care: opportunities for service delivery,
      patient-doctor communication, self-management, shared decision making and
      research.

PMID- 29577774
TI  - Managing out of hours clinical photography at the University Hospitals Bristol.
AB  - In recent years, Medical Illustration at University Hospitals Bristol (UHBristol)
      NHS Foundation Trust has seen a steady increase in photography requests,
      including the need for out of hours photography provision. This paper details how
      Medical Illustration at UHBristol decided to manage an out of hours clinical
      photography service.

PMID- 29577775
TI  - Cancer Ward 12: art, medical science, literature and life.
AB  - Cancer Ward 12 is an ongoing creative project concerned with expressing and
      articulating, through art, the physical, emotional and social impact of a cancer
      diagnosis. The first stage of the project was carried out through an artist
      residency on the general oncology ward, locally known as Ward 12, at Singleton
      Hospital in Swansea, Wales, in November 2016, and this led to a public exhibition
      of artwork, launched in Swansea in May 2017. This paper focuses on the
      methodology and rationale behind the Cancer Ward 12 project, and on the nature of
      the relation between creative practice and medical science.

PMID- 29577776
TI  - Comparison of barbed unidirectional suture with figure-of-eight standard sutures
      in vaginal cuff closure in total laparoscopic hysterectomy.
AB  - The aim of the study was to compare postoperative vaginal cuff complications due
      to the use of barbed sutures (V-LocTM 180 unidirectional suture; Covidien,
      Mansfield, MA) and standard braided sutures (Vicryl(r); Ethicon Inc., Somerville,
      MA) during vaginal cuff closure of patients undergoing a total laparoscopic
      hysterectomy (TLH) due to benign diseases. Eighty-nine patients were in the
      standard suture group and 208 patients were included in the barbed suture group.
      Vaginal cuff dehiscence was identified in only three (3.3%) patients within the
      standard suture group and none in the barbed suture group. Five (5.6%) patients
      in the standard suture group and two (0.9%) patients in the barbed suture group
      developed postoperative cuff infection/cellulitis. Duration of the surgery was
      significantly shorter in the barbed suture group than in the standard suture
      group (p < .05). V-LocTM 180 unidirectional barbed suture, which is used during
      TLH for vaginal cuff closure, is an applicable, safe and tolerable alternative to
      a standard suture. IMPACT STATEMENT What is already known on this subject: Barbed
      sutures are a relatively new type of suture that include sharp barbs inserted on
      monofilament material in various configurations, and are used for approximating
      tissues without any need for surgical knotting. They have increasingly been used
      in obstetrics and gynaecology in recent years, particularly in total laparoscopic
      hysterectomy and laparoscopic myomectomy. At present, there are a limited number
      of studies of V-LocTM suture in the literature. What the results of this study
      add: We demonstrated that barbed sutures used for enabling vaginal cuff integrity
      did not cause major morbidity and mortality for the patient. We suggest that V
      LocTM 180 barbed sutures offer a practical, safe and tolerable alternative for
      surgeons because they are easy to use, do not cause a significant increase in
      vaginal cuff complications, and shorten the operating time. Our study with V
      LocTM 180 unidirectional barbed suture is the second largest series after the
      study of Cong et al. What the implications are of these findings for clinical
      practice and/or further research: We believe that the barbed suture, the surgery
      results of which are openly discussed in our study, will be more prominent in
      clinical practice owing to the shortened operating time, and that the use of
      these sutures does not cause a significant increase in vaginal cuff
      complications.

PMID- 29577777
TI  - Factors associated with spontaneous perineal lacerations in deliveries without
      episiotomy in a university maternity hospital in the city of Recife, Brazil: a
      cohort study.
AB  - OBJECTIVES: The objective of this study is to determine factors associated with
      spontaneous perineal laceration in low-risk pregnant women who delivered
      vaginally without episiotomy in a university maternity hospital in Recife,
      Pernambuco, Brazil. METHODS: A prospective cohort study was conducted with 222
      low-risk, full-term pregnant women admitted in labor with a single fetus in
      cephalic presentation. Women with malformed fetuses were excluded from the study.
      The variables analyzed were: the frequency and severity of lacerations, the
      women's biological, sociodemographic, clinical and obstetrical characteristics,
      neonatal characteristics, and data on their deliveries and procedures. For the
      data analysis, risk ratios and their 95% confidence intervals were calculated. A
      significance level of 5% was adopted and multiple regression analysis was
      performed. RESULTS: Spontaneous first-degree perineal tears were registered in
      47% of the women, second-degree tears in 31%, and third degree tears in only
      1.8%. There were no cases of fourth-degree tears. Having experienced normal
      childbirth previously constituted a protective factor against vaginal tearing (OR
      =  0.46; 95%CI: 0.23-0.91; p = .027). CONCLUSION: The principal protective factor
      against spontaneous lacerations was having experienced normal childbirth
      previously. Intrapartum strategies aimed at protecting the perineum and pelvic
      floor muscle training during prenatal care should be encouraged in these women.

PMID- 29577778
TI  - Management of Postfasciotomy Wounds and Skin Defects Following Complex Vascular
      Trauma to the Extremities Using the External Tissue Extender System.
AB  - Management of large postfasciotomy wounds and/or skin and soft tissue defects
      after major vascular trauma to the extremities can be challenging. The External
      Tissue Extender (Blomqvist; ETE), a skin-stretching device, which consists of
      silicone tapes and plastic stoppers, approximates wound margins and facilitates
      delayed primary closure. We describe our experience with the use of ETE in 5
      patients (4 males) with a total of 8 wounds (7 postfasciotomy, 1 soft tissue
      defect) over the past 12 years. The mean patient age was 32 (range 17-61) years.
      The wounds involved the lower limb in 3 patients and the upper limb in 2, whereas
      the injured arteries were the popliteal in 3, the axillary in 1, and the brachial
      in 1. The mean wound length was 24 cm (range 9-37 cm), and the mean number of ETE
      silicone tapes used per wound was 13 (range 5-19). The median duration of ETE
      therapy was 7 days (range 4-7). ETE therapy resulted in sufficient wound
      approximation to allow complete closure with conventional suturing in 7 out of
      the 8 wounds. Of these, one developed infection that required drainage,
      debridement, and resuturing. All wounds achieved satisfactory healing status and
      all limbs had been salvaged. In conclusion, the ETE is a useful, easy-to-use, and
      simple adjunct that may facilitate delayed primary closure of large
      postfasciotomy wounds or extensive skin and soft tissue defects following complex
      vascular trauma to the extremities.

PMID- 29577779
TI  - A review in gait rehabilitation devices and applied control techniques.
AB  - PURPOSE: The aim of this review is to analyse the different existing technologies
      for gait rehabilitation, focusing mainly in robotic devices. Those robots help
      the patient to recover a lost function due to neurological gait disorders,
      accidents or after injury. Besides, they facilitate the identification of normal
      and abnormal features by registering muscle activity providing the doctor
      important data where he can observe the evolution of the patient. METHOD: A deep
      literature review was realized using selected keywords considering not only the
      most common medical and engineering databases, but also other available sources
      that provide information on commercial and scientific gait rehabilitation
      devices. The founded literature for this review corresponds to control techniques
      for gait rehabilitation robots, since the early seventies to the present year.
      RESULTS: Different control strategies for gait analysis in rehabilitation devices
      have been developed and implemented such as position control, force and impedance
      control, haptic simulation, and control of EMG signals. These control techniques
      are used to analyze the force of the patient during therapy, compensating it with
      the force generated by the mechanism in the rehabilitation device. It is observed
      that the largest number of studies reported, focuses on the impedance control
      technique. Leading to include new control techniques and validate them using the
      necessary protocols with ill patients, obtaining reliable results that allows a
      progressive and active rehabilitation. CONCLUSIONS: With this exhaustive review,
      we can conclude that the degree of complexity of the rehabilitation device
      influences in short and long-term therapeutic results since the movements become
      more controlled. However, there is still a lot of work in the sense of motion
      control in order to perform trajectories that are more alike the natural
      movements of humans. There are many control techniques in other areas, which seek
      to improve the performance of the process. These techniques may possibly be
      applicable in gait rehabilitation devices, obtaining controllers that are more
      efficient and that adapts to different people and the necessities that entail
      every disease. Implications for Rehabilitation Rehabilitation helps people to
      improve the activities of their daily life, allowing them to observe their
      progress in the functional abilities as the months pass by with intensive and
      repetitive therapies. There is a mobility issue when the patient needs to move to
      the hospital or to the laboratory, which is not always feasible. For overcoming
      it, patients use the equipment at home to perform their daily therapy. However,
      they need the sufficient knowledge about its operation, also about the
      therapeutic movements, the therapy duration and the movement speed. Besides, is
      necessary to place the equipment in a proper and lively environment that helps to
      forget or reduce pain while the patient moves his joints progressively. The
      purpose of robotic rehabilitation devices is to generate repetitive and
      progressive movements, according to the motor disability. There are training
      trajectories to follow, which motivate patients to generate active movements. The
      benefits of robotic rehabilitation depend on the ability of each patient to adapt
      to the speed and load variations generated by the device, improving and
      reinforcing motor functions in therapy, especially in patients with advanced
      disabilities in early rehabilitation. Multi-joint rehabilitation devices are more
      effective than single-joint rehabilitation devices because they involve a higher
      number of muscles in the therapy. The greater the number of degrees of freedom
      (DoF) of the device, it cushions its effect in the patient because the inertia is
      reduced and higher torques are generated. The assistive technological devices
      allows to explore different rehabilitation techniques that motivate the patient
      in therapy, increasing appropriately the energy and pressure in the blood which
      is reflected in gradually recovering his ability to walk.

PMID- 29577780
TI  - Random placenta margin incision for control hemorrhage during cesarean delivery
      complicated by complete placenta previa: a prospective cohort study.
AB  - INTRODUCTION: Complete placenta previa (CPP) is one of the most problematic types
      of abnormal placenta, which is further complicated by placenta accreta or
      percreta that can unexpectedly lead to catastrophic blood loss, infection,
      multiple complications, emergency hysterectomy, and even death. The present study
      aimed to assess the efficacy of random placenta margin incision in controlling
      intraoperative and total blood loss during cesarean section for CPP women.
      METHODS: A prospective cohort study, including a total of 100 consecutive
      pregnant women with CPP, was performed at a tertiary university-affiliated
      medical center between March 2016 and July 2017. All of them underwent random
      placenta margin incision, and intraoperative and total blood loss were analyzed.
      Through antenatal diagnosis using color Doppler, women were further divided into
      abnormally invasive placenta (AIP) and non-AIP groups, and anterior and posterior
      placenta groups. The protocol was registered with the Clinical Trial Registry
      under registration number NCT02695069. RESULTS: Mean maternal age and gestational
      age at delivery were 32.26 +/- 5.03 years old and 36.21 +/- 2.07 weeks,
      respectively. Total duration of the surgical procedure time was 52.50 (42.43
      64.00) min. Median estimated intraoperation blood loss was 746.43 (544.44
      1092.86) ml. Total blood loss was 875.00 (604.50-1196.67) ml, and 38 (38.0%) had
      post-partum hemorrhage. The change from baseline in the median hemoglobin level
      was -0.33 (6.00-13.20). No women underwent hysterectomy due to massive hemorrhage
      during the study period. No women had an intraoperative urinary bladder injury,
      postoperative wound infection, and required relaparotomy, owing to intra
      abdominal bleeding. The median hospitalization time was 5.41 (4.18-7.58) d.
      CONCLUSION: The random placenta margin incision may be a potentially valuable
      surgical procedure to control the volumes of intraoperative and postoperative
      blood loss and reduce the incidence of postpartum hemorrhage among women with
      complete placenta previa.

PMID- 29577781
TI  - Kurtosis-Based Detection of Intracranial High-Frequency Oscillations for the
      Identification of the Seizure Onset Zone.
AB  - Pathological High-Frequency Oscillations (HFOs) have been recently proposed as
      potential biomarker of the seizure onset zone (SOZ) and have shown superior
      accuracy to interictal epileptiform discharges in delineating its anatomical
      boundaries. Characterization of HFOs is still in its infancy and this is
      reflected in the heterogeneity of analysis and reporting methods across studies
      and in clinical practice. The clinical approach to HFOs identification and
      quantification usually still relies on visual inspection of EEG data. In this
      study, we developed a pipeline for the detection and analysis of HFOs. This
      includes preliminary selection of the most informative channels exploiting
      statistical properties of the pre-ictal and ictal intracranial EEG (iEEG) time
      series based on spectral kurtosis, followed by wavelet-based characterization of
      the time-frequency properties of the signal. We performed a preliminary
      validation analyzing EEG data in the ripple frequency band (80-250 Hz) from six
      patients with drug-resistant epilepsy who underwent pre-surgical evaluation with
      stereo-EEG (SEEG) followed by surgical resection of pathologic brain areas, who
      had at least two-year positive post-surgical outcome. In this series, kurtosis
      driven selection and wavelet-based detection of HFOs had average sensitivity of
      81.94% and average specificity of 96.03% in identifying the HFO area which
      overlapped with the SOZ as defined by clinical presurgical workup. Furthermore,
      the kurtosis-based channel selection resulted in an average reduction in
      computational time of 66.60%.

PMID- 29577782
TI  - Anatomically corrected malposition of the great arteries: a challenging fetal
      diagnosis.
AB  - Anatomically corrected malposed great arteries are uncommon and benign entity.
      Basically, this occurs with ventriculoarterial concordance in which the great
      vessels arise parallel instead of a twisting fashion. In this manuscript, we
      described two cases in which the antenatal diagnosis of anatomically corrected
      malposition of great arteries was suspected and confirmed during the postnatal
      period. During the fetal life, this diagnosis remains a challenge and this
      condition is often misdiagnosed as the transposition of the great arteries (TGA).
      Differently to TGA, anatomically corrected malposition of the great arteries may
      not require any cardiac surgical intervention depending on the associated cardiac
      anomalies. Indeed, postnatal examination for concerns related to anomalies that
      can be associated with this condition, such as anomalous origins of coronary
      arteries and left ventricular outflow tract obstruction, should be performed.

PMID- 29577783
TI  - Chasing as a model of psychogenic stress: characterization of physiological and
      behavioral responses.
AB  - Being chased by a predator or a dominant conspecific can induce significant
      stress. However, only a limited number of laboratory studies have employed
      chasing by itself as a stressor. In this study, we developed a novel stress
      paradigm in which rats were chased by a fast-moving object in an inescapable
      maze. In Experiment 1, defensive behaviors and stress hormone changes induced by
      chasing stress were measured. During the chasing stress, the chasing-stress group
      (n = 9) froze and emitted 22-kHz ultrasonic vocalizations (USVs), but the no
      chasing control group (n = 10) did not. Plasma corticosterone levels
      significantly increased following the chasing and were comparable to those of the
      restraint-stress group (n = 6). In Experiment 2, the long-lasting memory of the
      chasing event was tested after three weeks. The chasing-stress group (n = 15)
      showed higher levels of freezing and USV than the no-chasing group (n = 14) when
      they were presented with the tone associated with the object's chasing action.
      Subsequently, the rats were subjected to Pavlovian threat conditioning with a
      tone as a conditioned stimulus and footshock as an unconditioned stimulus. The
      chasing-stress group showed higher levels of freezing and USV during the
      conditioning session than the no-chasing group, indicating sensitized defensive
      reactions in a different threat situation. Taken together, the current results
      suggest that chasing stress can induce long-lasting memory and sensitization of
      defensive responses to a new aversive event as well as immediate, significant
      stress responses.

PMID- 29577785
TI  - Botulism in pregnancy - a clinical approach to diagnosis and management.
AB  - Botulism is a life-threatening toxin mediated disease that often presents with a
      sudden rapid onset of paralysis of their skeletal muscles with subsequent
      respiratory compromise and sudden death. Given the natural physiological changes
      during pregnancy, pregnant women with botulism may experience a more exaggerated
      course and have worse outcomes compared to nonpregnant women. Medical providers
      caring for such patients should not only maintain a high level of suspicion for
      botulism, but administration of an antitoxin early in their care can help reduce
      morbidity and mortality, while awaiting confirmatory laboratory results. It is
      not uncommon for a medical provider caring for these women to mistakenly
      associate the signs and symptoms associated with botulism with pregnancy-related
      findings; therefore, this article illustrates a clinical algorithmic approach to
      caring for these women, including a systematic approach to establishing a
      diagnosis and management plan for pregnant women with botulism.

PMID- 29577784
TI  - Updated standard operating procedures for electrochemotherapy of cutaneous
      tumours and skin metastases.
AB  - Electrochemotherapy is now in routine clinical use to treat cutaneous metastases
      of any histology, and is listed in national and international guidelines for
      cutaneous metastases and primary skin cancer. Electrochemotherapy is used by
      dermatologists, surgeons, and oncologists, and for different degrees and
      manifestations of metastases to skin and primary skin tumours not amenable to
      surgery. This treatment utilises electric pulses to permeabilize cell membranes
      in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer
      agents. Response rates, often after only one treatment, are very high across all
      tumour types. The most frequent indications are cutaneous metastases from
      malignant melanoma and breast cancer. In 2006, standard operating procedures
      (SOPs) were written for this novel technology, greatly facilitating introduction
      and dissemination of the therapy. Since then considerable experience has been
      obtained treating a wider range of tumour histologies and increasing size of
      tumours which was not originally thought possible. A pan-European expert panel
      drawn from a range of disciplines from dermatology, general surgery, head and
      neck surgery, plastic surgery, and oncology met to form a consensus opinion to
      update the SOPs based on the experience obtained. This paper contains these
      updated recommendations for indications for electrochemotherapy, pre-treatment
      information and evaluation, treatment choices, as well as follow-up.

PMID- 29577786
TI  - Complicated unsafe abortion in a Nigerian teaching hospital: pattern of morbidity
      and mortality.
AB  - Addressing unsafe abortion in developing countries may propel a rapid decline in
      overall maternal death. A retrospective review of patients with complicated
      unsafe abortion was conducted in a Nigerian Tertiary Hospital. In order to
      provide evidence that may inform policy changes, we describe patients' clinical
      profiles, abortion providers, and morbidity and mortality patterns. Of 3122
      gynaecological admissions, 231 (7.4%) had unsafe abortion-related complications.
      The majority (53.2%) of admissions were between 16 and 25 years. Single women
      constituted 51% while 57% were nulliparous. Common presentations were abdominal
      pain (62%), fever (54%) and vaginal bleeding (53%). The most frequent
      complications were anaemia (55%) and retained products of conception (47%).
      Doctors reportedly performed 42% of abortions. There were 392 maternal
      mortalities; 39 (9.9%) from unsafe abortions and sepsis was responsible in 31
      (80%) patients. Abortion remains a major public health issue. Youths are mostly
      involved. Doctors were reportedly the highest abortion providers. Mortality is
      high, occurring mostly from sepsis. Impact Statement What is already known on
      this subject? Doctors are reported as being involved in a high proportion of
      unsafe abortions in low and middle income countries where abortion remains a
      significant contributor to maternal mortality and morbidity. What the results of
      this study add? Our study agrees with existing literature that doctors reportedly
      performed most of the unsafe abortions. It also found that doctors were reported
      as abortion providers in the majority (35.9%) of those unsafe abortions that
      ended in mortality. What the implications are of these findings for clinical
      practice and/or further research? There is a need to conduct studies that will
      verify the status of abortion providers rather than rely on clients' report; and
      also inspect facilities to confirm adherence to minimum medical standards. Such
      research findings will be needed prior to local and possibly national healthcare
      interventions and policy changes.

PMID- 29577787
TI  - Clinical and economic outcomes associated with the use of fluticasone propionate
      250 mcg and salmeterol 50 mcg combination versus tiotropium bromide 18 mcg as
      initial maintenance treatment for chronic obstructive pulmonary disease in
      managed care.
AB  - AIMS: To examine the clinical and economic outcomes associated with the use of
      long-acting bronchodilators for initial maintenance treatment of chronic
      obstructive pulmonary disease (COPD) by analyzing health insurance claims data in
      the US. METHODS: A retrospective, observational, matched cohort study used health
      insurance claims data (January 2008 to June 2013) to assess COPD-related outcomes
      for subjects aged >=40 years. Subjects were assigned to a study cohort according
      to the first observed prescription fill for a long-acting bronchodilator
      (fluticasone propionate 250 mcg/salmeterol 50 mcg [FSC] or tiotropium bromide 18
      mcg [TIO]). The analysis period for each subject comprised a 1-year pre-index
      date and 1-year post-index date. Primary outcome measure was total COPD-related
      costs per-patient per-year (PPPY) during the follow-up period. Secondary outcome
      measures included COPD-related exacerbations and the components of COPD-related
      costs. RESULTS: Overall, 24,040 subjects were identified; the analysis sample
      consisted of 19,090 subjects (9,545 per cohort) with no significant differences
      between cohorts. Mean COPD-related total costs PPPY were numerically lower among
      the FSC cohort; however, the difference was not statistically significant ($2,224
      [+/-4,108] vs $2,352 [+/-3,721], p = .057). There was no difference between
      cohorts for COPD-related medical costs (p = .894). COPD-related pharmacy costs
      were significantly, yet modestly, lower in the FSC cohort compared with the TIO
      cohort ($1,160 [+/-1,106] vs 1,275 [+/-1,110], p < .001). There were no
      statistically significant differences in the rate or number of exacerbations
      between the matched cohorts. LIMITATIONS: While propensity scoring achieved
      balance in baseline characteristics, some residual confounding unobserved in the
      database may be present. CONCLUSIONS: Few clinical and economic differences
      between subjects initiating maintenance therapy with FSC or TIO were observed.

PMID- 29577788
TI  - Barrels XXX meeting report: Barrels in Baltimore.
AB  - The Barrels meeting annually brings together researchers focused on the rodent
      whisker to cortical barrel system prior to the Society for Neuroscience meeting.
      The 2017 meeting focused on the classification of cortical interneurons, the role
      interneurons have in shaping brain dynamics, and finally on the circuitry
      underlying oral sensations. The meeting highlighted the latest advancements in
      this rapidly advancing field.

PMID- 29577789
TI  - A sandwich technique (N&H variation technique) to reduce blood loss during
      cesarean delivery for complete placenta previa: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of A sandwich technique Nahla & Hany
      variation (N&H) technique versus stepwise uterine devascularization on blood loss
      during cesarean section (CS) in patients with complete placenta previa. METHODS:
      The study was single-blind randomized controlled trial carried out in a tertiary
      University Hospital between March 2015 to March 2018. We included patients
      scheduled for CS due to complete placenta previa. They were randomly allocated to
      group (I) managed by stepwise uterine devascularization, group (II) managed by
      double transverse compression suture at the lower uterine segment plus
      intrauterine inflated Foley's catheter Balloon (H&N variation sandwich) at the
      lower uterine segment. The primary outcome was the amount of total estimated
      blood loss both intra- and post-operative. RESULTS: One hundred and six patients
      were enrolled (n = 53 in each group). There was a great reduction in
      intraoperative blood loss in group II 570 (400-1300) compared with Group I 1030
      (500-1540) (p = .0001), or blood in the intraabdominal drain in group II than
      group I (p = .0001) Also, there was no significant reduction in postoperative
      vaginal bleeding. Hence, the total estimated blood loss in group II 750 (550
      1580) showed significant reduction compared with group I 1350 (780-1800) (p =
      .0001). CONCLUSIONS: N&H variation sandwich technique in the management of
      complete placenta previa is a simple technique, safe and effective to decrease
      blood loss.

PMID- 29577790
TI  - Parent Psychological Distress in the Neonatal Intensive Care Unit Within the
      Context of the Social Ecological Model: A Scoping Review.
AB  - BACKGROUND: Neonatal intensive care unit (NICU) parents are at risk for
      psychological distress and impaired mental health, and statistics related to
      parent psychological distress vary. OBJECTIVE: To determine the scope of
      literature regarding the mental health and psychosocial well-being of parents in
      the NICU. DESIGN: A scoping review within the Arksey and O'Malley framework and
      the SEM was undertaken to answer, "What factors contribute to parent's mental
      health in the NICU?" A systematic review of the literature was performed using
      the PRISMA methodology. RESULTS: Common socioeconomic factors and infant and
      parent characteristics may place parents at a greater risk for developing
      distress. History of mental illness, family cohesion, birth trauma, altered
      parenting role, gestational age, birth weight, and severity of
      prematurity/illness emerged as themes. CONCLUSION: Further research is required
      to provide a standard for the screening and assessment of parents' mental health
      and psychosocial well-being during a NICU hospitalization. The experiences of
      nonbirth parents in the NICU should be explored to examine the effects of the
      hospitalization on all types of parents.

PMID- 29577791
TI  - Automated detection and classification of the proximal humerus fracture by using
      deep learning algorithm.
AB  - Background and purpose - We aimed to evaluate the ability of artificial
      intelligence (a deep learning algorithm) to detect and classify proximal humerus
      fractures using plain anteroposterior shoulder radiographs. Patients and methods 
      1,891 images (1 image per person) of normal shoulders (n = 515) and 4 proximal
      humerus fracture types (greater tuberosity, 346; surgical neck, 514; 3-part, 269;
      4-part, 247) classified by 3 specialists were evaluated. We trained a deep
      convolutional neural network (CNN) after augmentation of a training dataset. The
      ability of the CNN, as measured by top-1 accuracy, area under receiver operating
      characteristics curve (AUC), sensitivity/specificity, and Youden index, in
      comparison with humans (28 general physicians, 11 general orthopedists, and 19
      orthopedists specialized in the shoulder) to detect and classify proximal humerus
      fractures was evaluated. Results - The CNN showed a high performance of 96% top-1
      accuracy, 1.00 AUC, 0.99/0.97 sensitivity/specificity, and 0.97 Youden index for
      distinguishing normal shoulders from proximal humerus fractures. In addition, the
      CNN showed promising results with 65-86% top-1 accuracy, 0.90-0.98 AUC, 0.88/0.83
      0.97/0.94 sensitivity/specificity, and 0.71-0.90 Youden index for classifying
      fracture type. When compared with the human groups, the CNN showed superior
      performance to that of general physicians and orthopedists, similar performance
      to orthopedists specialized in the shoulder, and the superior performance of the
      CNN was more marked in complex 3- and 4-part fractures. Interpretation - The use
      of artificial intelligence can accurately detect and classify proximal humerus
      fractures on plain shoulder AP radiographs. Further studies are necessary to
      determine the feasibility of applying artificial intelligence in the clinic and
      whether its use could improve care and outcomes compared with current orthopedic
      assessments.

PMID- 29577792
TI  - Relation of Diabetes to Cognitive Function in Hispanics/Latinos of Diverse
      Backgrounds in the United States.
AB  - OBJECTIVES: To examine the association between diabetes and cognitive function
      within U.S. Hispanics/Latinos of Central American, Cuban, Dominican, Mexican,
      Puerto Rican, and South American background. METHOD: This cross-sectional study
      included 9,609 men and women (mean age = 56.5 years), who are members of the
      Hispanic Community Health Study/Study of Latinos. We classified participants as
      having diabetes, prediabetes, or normal glucose regulation. Participants
      underwent a neurocognitive battery consisting of tests of verbal fluency, delayed
      recall, and processing speed. Analyses were stratified by Hispanic/Latino
      subgroup. RESULTS: From fully adjusted linear regression models, compared with
      having normal glucose regulation, having diabetes was associated with worse
      processing speed among Cubans (beta = -1.99; 95% CI [confidence interval] = [
      3.80, -0.19]) and Mexicans (beta = -2.26; 95% CI = [-4.02, -0.51]). Compared with
      having normal glucose regulation, having prediabetes or diabetes was associated
      with worse delayed recall only among Mexicans (prediabetes: beta = -0.34; 95% CI
      = [-0.63, -0.05] and diabetes: beta = -0.41; 95% CI = [-0.79, -0.04]). No
      associations with verbal fluency. DISCUSSION: The relationship between diabetes
      and cognitive function varied across Hispanic/Latino subgroup.

PMID- 29577793
TI  - Can we predict levator ani muscle avulsion in instrumental deliveries through
      intrapartum transperineal ultrasound?
AB  - INTRODUCTION: To determine whether intrapartum translabial ultrasound (ITU) is
      useful for the prediction of levator ani muscle (LAM) avulsions in instrumental
      deliveries (vacuum and forceps). MATERIALS AND METHODS: Prospective,
      observational study, including (1/2016 - 5/2016) 77 nulliparous women, with
      singleton pregnancies of >=37 weeks of gestation and with cephalic presentation,
      who required vacuum or forceps instrumentation to complete the delivery. The ITU
      parameters evaluated were Angle of Progression (AoP), Progression Distance (PD),
      Head Direction (HD), and Midline Angle (MLA), both at rest and with maternal
      push. Evaluation of LAM avulsion was performed at 6 months postpartum with 3-4D
      transperineal ultrasound. Complete avulsion was defined as an abnormal insertion
      of LAM in the lower pubic branch identified in all three central slices. RESULTS:
      Data from 48 nulliparous women were finally included in the study (34 vacuum and
      14 forceps). We observed no difference in obstetric parameters between the two
      study groups (group with avulsion of LAM -14 cases, 29.2% - and group without
      avulsion of LAM -34 cases, 70.8%). The "LAM avulsion group" had an AoP and a PD
      of 136.7 +/- 22.4 and 43.5 +/- 15.6, respectively, versus 141.6 +/- 21.3 and 47.2
      +/- 16.8 recorded in the group without avulsion (NS), respectively. We obtained a
      ROC curve for AoP and PD with a push of 0.66 (95% CI, 0.28-1.00) and 0.57 (95%
      CI, 0.39-0.75), respectively. CONCLUSIONS: ITU is not a useful technique to
      predict the occurrence of LAM avulsion in instrumental deliveries with vacuum or
      forceps.

PMID- 29577794
TI  - Pelvic Ring Fracture Accompanying Traumatic Thrombosis and Posterior Peritoneum
      Hernia in a 2-Year-Old Child: A Case Report.
AB  - A 2-year-old girl who was badly injured by a forklift, was presented to the
      emergency department with open and comminuted pelvic fracture, dislocation of
      right sacroiliac jointand femoral neck fracture on the left side. An urgent
      debridement was performed. However, postoperatively, the girl had apparent
      abdominal distension. The results of contrast-enhanced CT implied that the
      intestineherniated through the fissure formed by dislocation of the sacroiliac
      joint, which was confirmed during the operation. Therefore, hernia repair and
      reduction of the sacroiliac joint were performed by a Multidisciplinary team.With
      regard to patient's age, the sacroiliac joint was reduced and sutured with two
      absorbable anchors. The fracture healed in the following 3 months after
      discharge.

PMID- 29577796
TI  - Microwave ablation compared to thyroidectomy to treat benign thyroid nodules.
AB  - OBJECTIVE: Benign thyroid nodules occur commonly but only require treatment when
      symptomatic. Surgical treatment, once routine, has been replaced by newer
      technologies, such as microwave ablation (MWA). The aim of this study was to
      assess the efficacy, tolerability and cost of MWA compared to surgery to treat
      benign thyroid nodules. METHODS: After obtaining ethical approval and informed
      consent, a prospective trial was conducted with 52 patients who had symptomatic
      benign thyroid nodules. Patients were randomly assigned to receive MWA or
      surgical treatment. The volume reduction ratio (VRR), thyroid function,
      complications, HRQoL, costs and some parameters were compared. RESULTS: MWA
      reduced mean nodule volume by 72.3% at 3 months, 84.5% at 6 months and 92.4% at
      12 months as effective as surgery in inactivating nodules, and thyroid
      dysfunction did not occur during 12-month follow-up for those receiving MWA.
      Although both MWA and surgery were safe, patients undergoing MWA had fewer cases
      of complications and rarely reported pain. The MWA group was superior to the
      surgery group in length of stay, postoperative scar length and the operation
      time. Compared to patients who underwent surgery, those who underwent MWA had
      better general health and mental health scores at 6 months and 12 months. The
      mean total cost of the MWA group was lower than that of the surgery group.
      CONCLUSION: MWA can significantly reduce nodule volume and nodule-related
      symptoms with more rapid recovery, more pleasing esthetic outcomes, less
      physiologic disruption and less expense compared to the surgery.

PMID- 29577795
TI  - Regional citrate-calcium anticoagulation during polymyxin-B hemoperfusion: A case
      series.
AB  - INTRODUCTION: So far, only heparin-based anticoagulation has been proposed during
      polymyxin-B hemoperfusion. However, postsurgical septic patients can be at high
      risk of bleeding due to either surgical complications or septic coagulation
      derangement. Consequently, heparin should not represent in some cases the
      anticoagulation regimen of choice in this type of patients. METHODS AND RESULTS:
      We present a case series of four postsurgical septic patients treated with
      polymyxin-B hemoperfusion using regional citrate anticoagulation. All the
      treatments were performed without complications. During each treatment, there
      were no episodes of filter clotting, no bleeding, and no metabolic complications
      for any of the patients. CONCLUSION: To our knowledge, this is the second
      published report on the use of citrate anticoagulation during polymyxin-B
      hemoperfusion. Our case series continued to show that regional citrate
      anticoagulation regimen is feasible and safe during polymyxin-B hemoperfusion
      treatment in postsurgical septic patients.

PMID- 29577797
TI  - Using Behavior Sequence Analysis to Map Serial Killers' Life Histories.
AB  - The aim of the current research was to provide a novel method for mapping the
      developmental sequences of serial killers' life histories. An in-depth
      biographical account of serial killers' lives, from birth through to conviction,
      was gained and analyzed using Behavior Sequence Analysis. The analyses highlight
      similarities in behavioral events across the serial killers' lives, indicating
      not only which risk factors occur, but the temporal order of these factors.
      Results focused on early childhood environment, indicating the role of parental
      abuse; behaviors and events surrounding criminal histories of serial killers,
      showing that many had previous convictions and were known to police for other
      crimes; behaviors surrounding their murders, highlighting differences in victim
      choice and modus operandi; and, finally, trial pleas and convictions. The present
      research, therefore, provides a novel approach to synthesizing large volumes of
      data on criminals and presenting results in accessible, understandable outcomes.

PMID- 29577798
TI  - Effects of Art Intervention Program for Siblings of Children With Cancer: A Pilot
      Study.
AB  - Siblings of children with cancer often experience negative feelings, and art
      intervention can help them express their feelings and overcome hardships. This
      study aimed to develop an Art Intervention Program to improve the psychological
      adaptation of siblings of children with cancer and to evaluate its effects.
      Participants were seventeen 7- to 10-year-old siblings of children with cancer.
      The program comprised 12 sessions conducted once a week. The effects of the
      intervention were assessed in terms of self-esteem, anxiety, depression, and
      problem behavior. Self-esteem significantly improved after intervention compared
      with pretest. Children showed improved scores in externalizing problems and total
      behavior problems; however, anxiety and depression did not change. The study
      results indicated that the art intervention program helped improve the self
      esteem and helped reduce somatic symptoms, aggressiveness, externalizing
      problems, and emotional instability among problem behaviors of siblings of
      children with cancer. However, the study was limited by its small sample size and
      the lack of a control group. Therefore, the study design allows no firm
      conclusions, and a randomized controlled trial is needed to investigate the
      effectiveness of the program.

PMID- 29577799
TI  - What Affects the Demand for Long-Term Care Insurance? A Study of Middle-Aged and
      Older Adults in Hong Kong.
AB  - Despite the potential of private insurance in financing long-term care (LTC), its
      coverage remains rather limited. This study is built on a comprehensive framework
      to examine the demand for LTC insurance in Hong Kong, a rapidly aging Asian
      society. A telephone survey was conducted in 2016 to collect data that formed a
      sample of 1,474 middle-aged and older adults. Multivariate analysis reveals more
      nuanced characteristics of Hong Kong middle-aged and older adults who tend to
      show a demand for LTC insurance, including: (a) being younger, better educated,
      relatively high status, and financially literate; (b) living with children but
      reluctant to be a burden on the family; (c) being in a better financial situation
      and able to afford premiums; and (d) anticipation of LTC needs and dependence,
      and a preference for formal care. This study offers preliminary evidence to
      understand the demand structure of the LTC insurance market in an Asian society.

PMID- 29577800
TI  - Cognitive Social Capital and Formal Volunteering Among Older Adults in Urban
      China: Does Gender Matter?
AB  - This study examined the moderating effect of gender on the relationship between
      cognitive social capital and formal volunteering among older adults in urban
      China. Cognitive social capital refers to individuals' perceptions of their
      social relationships in local communities. We used quota sampling to recruit 456
      older adults aged 60 years and older from 16 communities of Gusu district, Suzhou
      city, in late 2015. Multiple group analysis was used to examine the proposed
      model. Gender had a moderating effect on the relationship between cognitive
      social capital and volunteering. The associations between cognitive social
      capital and volunteering were higher among older men than older women. The
      findings highlight the important role of cognitive social capital in influencing
      formal volunteering among older adults in urban Chinese contexts. The findings
      are particularly important for enhancing volunteering among older adults across
      different social and economic backgrounds. Policy and intervention implications
      are discussed.

PMID- 29577801
TI  - Early Identification of Barriers and Facilitators to Self-Management Behaviors in
      Pediatric Patients With Sickle Cell Disease to Minimize Hematopoietic Cell
      Transplantation Complications.
AB  - Hematopoietic cell transplantation (HCT) is an elective, curative treatment
      option for patients with sickle cell disease (SCD). Transplant requires extensive
      self-management behaviors to be successful. The purpose of this study was to
      describe potential barriers and facilitators to self-management in a group of
      pediatric patients with SCD prior to HCT and their medical outcomes post-HCT. A
      multiple case study approach was used to describe 4 pairs of transplant
      recipients grouped by age, donor type, and donor source. Each pair included a
      case with minimal and increased post-HCT complications. Complications included
      readmissions, graft-versus-host disease, systemic infections, and survival in the
      first year post-HCT. Variables were retrospectively collected and content
      analyzed to identify barriers and facilitators within and across pairs using
      existing self-management frameworks. While higher risk transplants experienced
      more complications, 3 of the 4 cases with increased complications had a larger
      number of modifiable barriers identified compared with those experiencing minimal
      complications. At least one modifiable barrier and multiple facilitators were
      identified in all cases. A standardized psychosocial assessment process with an
      established plan to mitigate barriers and promote facilitators to self-management
      is essential to optimize outcomes in patients with SCD undergoing elective HCT.

PMID- 29577802
TI  - Diameter of inflow as a predictor of radiocephalic fistula flow.
AB  - INTRODUCTION:: The optimal method for vascular access surveillance is largely
      unknown. A previous case-control study suggested a simplified anatomical measure
      obtained by Doppler ultrasound-the narrowest segment of the circuit or "minimal
      luminal diameter" may identify patients with a dysfunctional radiocephalic
      arteriovenous fistula. The relationship between minimal luminal diameter and
      access flow (Qa) in the radiocephalic arteriovenous fistula has not previously
      been studied. METHODS:: Patients undergoing Doppler ultrasound of a radiocephalic
      arteriovenous fistula over an 8-month period were identified retrospectively.
      Minimal luminal diameter was identified and demographic and clinical data were
      collected. Qa was estimated by Doppler estimation of brachial artery flow. The
      relationship between minimal luminal diameter and Qa was examined by correlation
      and using different levels of minimal luminal diameter as a simplified measure to
      detect or exclude low Qa (<600 mL/min). RESULTS:: A total of 81 Doppler
      ultrasound scans were performed. In all, 26 scans demonstrated brachial artery
      flow <600 mL/min. Simple logistic regression indicated a weak statistical
      relationship between the minimal luminal diameter and Qa (R2 = 0.27, p < 0.01).
      Minimal luminal diameter performed poorly as a marker of low Qa with low
      specificity, however, showed high negative predictive value for ruling out low Qa
      at a minimal luminal diameter of 3.2 mm or higher (94%). Qa estimated by brachial
      artery flow correlated well with Qa estimated by indicator dilution (R2 = 0.83, p
      < 0.01) without significant mean difference or proportional bias. CONCLUSION::
      Minimal luminal diameter correlates weakly with Qa. Low minimal luminal diameter
      values should not be used in isolation to determine low Qa for a radiocephalic
      arteriovenous fistula. Conversely, minimal luminal diameter >3.2 mm largely
      excludes a low-flow radiocephalic arteriovenous fistula in this cohort. Brachial
      artery flow is a reasonable measure of Qa in comparison with indicator dilution.

PMID- 29577803
TI  - Corrigendum.
AB  - Jung Ye-Ha, Kim H, Jeon SY, Kwon JM, Lee D, Choi Soo-Hee and Kang Do-Hyung.
      Aberrant interactions of peripheral measures and neurometabolites with lipids in
      complex regional pain syndrome using magnetic resonance spectroscopy: A pilot
      study. Mol Pain 2018; 14: doi: 10.1177/1744806917751323 In this article, the
      authors inadvertently changed the name of the Lip dependents and forgot to
      mention the usage of the findings. This is corrected for all the versions of the
      article and the updated text is mentioned below. The authors regret this error.
      Lip09-dependent right thalamus and Lip13a-dependent left thalamus may be
      important to elucidate abnormal interactions between lipids in the central
      thalamus and peripheral measures in CRPS patients, suggestive of unique
      mechanisms underlying lipidassociated pathophysiology in CRPS, These findings may
      be used to develop personalized therapies according to the dominant side of the
      thalamus (right versus left) and the presence and interactions of specific
      metabolites.

PMID- 29577804
TI  - Inflectional Morphology in Fluent Aphasia: A Case Study in a Highly Inflected
      Language.
AB  - Inflectional morphology difficulties are typically reported in non-fluent aphasia
      with agrammatism, but a growing number of studies show that they can also be
      present in fluent aphasia. In agrammatism, morphological difficulties are
      conceived as the consequence of impaired phonological encoding and would affect
      regular verbs more than irregular verbs. However, studies show that inflectional
      morphology difficulties concern both regular and irregular verbs, and that their
      origin could be more conceptual/semantic in nature. Additionally, studies report
      more pronounced impairments for the processing of the past tense compared to
      other tenses. The goal of this study was to characterize the impairment of
      inflectional morphology in fluent aphasia. RY, a 69-year-old man with chronic
      fluent aphasia completed a short neuropsychological and language battery and
      three experimental tasks of inflectional morphology. The tasks assessed the
      capacity to select the correct inflected form of a verb based on time
      information, to access the time information included in an inflectional morpheme,
      and to produce verbs with tense inflection. His performance was compared to a
      group of five adults without language impairments. Results showed that RY had
      difficulties selecting the correct inflected form of a verb, accessing time
      information transmitted by inflectional morphemes, and producing inflected verbs.
      His difficulties affected both regular and irregular verbs, and verbs in the
      present, past, and future tenses. The performance also shows the influence of
      processing limitations over the production and comprehension of inflectional
      morphology. More studies of inflectional morphology in fluent aphasia are needed
      to understand the origin of difficulties.

PMID- 29577806
TI  - Corrigendum.
AB  - Callesen J, Richter C, Kristensen C, et al. Test-retest agreement and reliability
      of the Six Spot Step Test in persons with multiple sclerosis. Mult Scler. Epub
      ahead of print 20 December 2017. DOI: 10.1177/1352458517745725 In this article,
      'Intraclass Correlation Coefficient' appeared incorrectly as 'Interclass
      Correlation Coefficient' on two occasions, once on line eight of the abstract and
      once on page four, on the first line of paragraph two. This error has now been
      corrected in the online version of the article.

PMID- 29577805
TI  - Impact of Cyrillic on Native English Speakers' Phono-lexical Acquisition of
      Russian.
AB  - We investigated the influence of grapheme familiarity and native language
      grapheme-phoneme correspondences during second language lexical learning. Native
      English speakers learned Russian-like words via auditory presentations containing
      only familiar first language phones, pictured meanings, and exposure to either
      Cyrillic orthographic forms (Orthography condition) or the sequence <XXX> (No
      Orthography condition). Orthography participants saw three types of written
      forms: familiar-congruent (e.g., <KOM>-[kom]), familiar-incongruent (e.g., <PAT>
      [ralphat]), and unfamiliar (e.g., <FIL>-[fil]). At test, participants determined
      whether pictures and words matched according to what they saw during word
      learning. All participants performed near ceiling in all stimulus conditions,
      except for Orthography participants on words containing incongruent grapheme
      phoneme correspondences. These results suggest that first language grapheme
      phoneme correspondences can cause interference during second language phono
      lexical acquisition. In addition, these results suggest that orthographic input
      effects are robust enough to interfere even when the input does not contain novel
      phones.

PMID- 29577807
TI  - Changing vision: a review of pharmacogenetic studies for treatment response in
      age-related macular degeneration patients.
AB  - Nonresponsiveness to age-related macular degeneration (AMD) treatments has become
      a growing concern in ophthalmology. Disparity among publications that have
      assessed pharmacogenetic (PGx) connections between AMD disease genes and
      treatments has delayed the implementation of PGx testing in AMD. We assessed all
      AMD PGx publications to identify the degree of agreement for publications within
      similar ethnic cohorts and worldwide, and the causes for differences in study
      outcomes. There are no accepted genotype-phenotype correlations, either within
      similar ethnic cohorts or worldwide. The diversity of measured outcomes,
      treatment protocols and statistical methods used may be causing this discrepancy.
      A universally accepted treatment protocol and the creation of agreed response
      group classification may bridge the gap between AMD PGx publications.

PMID- 29577808
TI  - Winners of the Third Annual TCN/AACN Student Project Competition.

PMID- 29577809
TI  - Spectrum of Neuromuscular Disorders With HyperCKemia From a Tertiary Care
      Pediatric Neuromuscular Center.
AB  - Elevated creatine kinase is a useful screening test in the diagnostic workup of
      patients with neuromuscular disorders. We did a retrospective study of children
      with hyperCKemia (>175 IU/L) who were followed in the neuromuscular program of a
      tertiary care pediatric center from 2005 to 2016. Patients with hyperCKemia were
      divided into 2 groups: myopathic and nonmyopathic. Within the myopathic group,
      there were 3 arbitrary subgroups based on creatine kinase values: A (creatine
      kinase >10 times normal), B (creatine kinase 5-10 times normal), and C (creatine
      kinase 1-5 times normal). The 3 major categories of myopathies across all the
      subgroups were muscular dystrophies (commonest) followed by metabolic myopathies
      and inflammatory myopathies. Among the nonmyopathic causes of hyperCKemia, spinal
      muscular atrophy was the commonest. Muscular dystrophies should be considered in
      children with hyperCKemia, muscle weakness, or calf hypertrophy, and metabolic
      myopathies to be considered in children with recurrent rhabdomyolysis.

PMID- 29577811
TI  - Are haplotypes in a single methotrexate pathway more predictive for response in
      rheumatoid arthritis than in different pathways?
AB  - Letter to the editor with respect to: Lima A, Bernardes M, Azevedo R, Seabra V
      and Medeiros R. Moving toward personalized medicine in rheumatoid arthritis: SNPs
      in methotrexate intracellular pathways are associated with methotrexate
      therapeutic outcome. Pharmacogenomics 17(15), 1649-1674 (2016).

PMID- 29577810
TI  - Pharmacologic targeting of endothelial Ca2+-activated K+ channels: A strategy to
      improve cardiovascular function.
AB  - Endothelial small and intermediate-conductance, Ca2+-activated K+ channels
      (KCa2.3 and KCa3.1, respectively) play an important role in the regulation of
      vascular function and systemic blood pressure. Growing evidence indicates that
      they are intimately involved in agonist-evoked vasodilation of small resistance
      arteries throughout the circulation. Small molecule activators of KCa2.x and 3.1
      channels, such as SKA-31, can acutely inhibit myogenic tone in isolated
      resistance arteries, induce effective vasodilation in intact vascular beds, such
      as the coronary circulation, and acutely decrease systemic blood pressure in
      vivo. The blood pressure-lowering effect of SKA-31, and early indications of
      improvement in endothelial dysfunction suggest that endothelial KCa channel
      activators could eventually be developed into a new class of endothelial targeted
      agents to combat hypertension or atherosclerosis. This review summarises recent
      insights into the activation of endothelial Ca2+ activated K+ channels in various
      vascular beds, and how tools, such as SKA-31, may be beneficial in disease
      related conditions.

PMID- 29577813
TI  - Scapular kinematics during scaption in competitive swimmers.
AB  - This study aimed (1) to describe and compare scapular kinematics between three
      groups of swimmers of different levels and a group of non-swimmers, and (2) to
      assess whether swimming practice alters the asymmetries in scapular kinematics
      between the dominant and non-dominant sides, both during unilateral arm raising
      and lowering in the scapular plane. Scapular kinematics were assessed bilaterally
      during arm raising and lowering in the scapular plane using an electromagnetic
      system in 42 healthy males, which were split into four groups: control (n = 11),
      adolescent elite swimmers (n = 11), adult elite swimmers (n = 10), and club-level
      adult swimmers (n = 10). One-Way ANOVA SPM(t) on two repeated measures showed
      that the three groups of swimmers had more protracted shoulder between 30 degrees
      and 90 degrees  of arm raising and lowering (p < .001). The three groups of
      swimmers presented no bilateral difference in scapular upward rotation, while the
      dominant scapula was more upwardly rotated than the non-dominant one between 74
      degrees  and 104 degrees  of arm elevation in the control group (p < .001). The
      scapula of adult elite swimmers was more internally rotated between 67 degrees 
      and 116 degrees  of humeral elevation during arm raising, and between 81 degrees 
      and 54 degrees  during arm lowering in comparison to the other swimming and
      control groups (p <= .02), who presented similar scapular positioning in internal
      rotation. In conclusion, the findings of the study pointed out that swimming
      practice generated protracted shoulders and removed bilateral differences in
      scapular upward rotation during scaption, while accumulation of swimming practice
      at elite level enlarged scapular internal rotation.

PMID- 29577814
TI  - A Two-Step Markov Processes Approach for Parameterization of Cancer State
      Transition Models for Low- and Middle-Income Countries.
AB  - Implementation of organized cancer screening and prevention programs in high
      income countries (HICs) has considerably decreased cancer-related incidence and
      mortality. In low- and middle-income countries (LMICs), screening and early
      diagnosis programs are generally unavailable, and most cancers are diagnosed in
      late stages when survival is very low. Analyzing the cost-effectiveness of
      alternative cancer control programs and estimating resource needs will help
      prioritize interventions in LMICs. However, mathematical models of natural cancer
      onset and progression needed to conduct the economic analyses are predominantly
      based on populations in HICs because the longitudinal data on screening and
      diagnoses required for parameterization are unavailable in LMICs. Models
      currently used for LMICs mostly concentrate on directly calculating the shift in
      distribution of cancer diagnosis as an evaluative measure of screening. We
      present a mathematical methodology for the parameterization of natural cancer
      onset and progression, specifically for LMICs that do not have longitudinal data.
      This full onset and progression model can help conduct comprehensive analyses of
      cancer control programs, including cancer screening, by considering both the
      positive impact of screening as well as any adverse consequences, such as over
      diagnosis and false-positive results. The methodology has been applied to breast,
      cervical, and colorectal cancers for 2 regions, under the World Health
      Organization categorization: Eastern Sub-Saharan Africa (AFRE) and Southeast Asia
      (SEARB). The cancer models have been incorporated into the Spectrum software and
      interfaced with country-specific demographic data through the demographic
      projections (DemProj) module and costing data through the OneHealth tool. These
      software are open-access and can be used by stakeholders to analyze screening
      strategies specific to their country of interest.

PMID- 29577815
TI  - The efficacy of drug-eluting stent for recurrent central venous restenosis in a
      patient undergoing hemodialysis.
AB  - INTRODUCTION: Recurrent central venous restenosis is problematic in patients with
      ipsilateral arteriovenous fistula. We report our experience using a drug-eluting
      stent for the treatment of recurrent central vein restenosis. CASE REPORT: A 60
      year-old man consulted our hospital because of recurrent swelling of his left
      upper limb with radial-cephalic arteriovenous fistula that originated in the
      distal forearm. More than 3 years prior, two bare-metal stents were placed for
      the obstructed lesions in the left subclavian and brachiocephalic venous lesions,
      and repeated balloon angioplasty for recurrent in-stent stenosis was performed
      approximately every 3 months. Angiography with iodinated contrast agents revealed
      an approximately 3-cm-long restenosis at the distal part of the bare-metal
      stents. One drug-eluting stent (Zilver PTX Drug-Eluting Peripheral Stent; Cook
      Medical, Bloomington, IN, USA) was deployed at the narrowing lesion, followed by
      balloon angioplasty. The stenotic lesion was successfully and safely dilated. The
      patient consulted our hospital 5.5 months after drug-eluting stent placement
      because of restenosis at the distal part of the drug-eluting stent, but only in a
      shorter segment than before. Freedom from clinically driven target-lesion
      revascularization (TLR) extended from 3.1 to 5.5 months after drug-eluting stent
      placement. Although additional implantation of the second drug-eluting stent was
      required 14.6 months after the first drug-eluting stent placement, freedom from
      TLR before/after the second drug-eluting stent placement extended from 4.4 months
      to more than 8.6 months. CONCLUSION: Drug-eluting stent placement is an effective
      strategy for recurrent central venous stenosis in patients with ipsilateral
      arteriovenous fistula. To our knowledge, this is the first report of drug-eluting
      stent placement for recurrent venous stenosis in a patient undergoing
      hemodialysis.

PMID- 29577816
TI  - CDE Pharmacists in the United States.
AB  - Purpose The purpose of the study was to identify current practice settings for
      Certified Diabetes Educators (CDEs) who are pharmacists. Following nurses and
      dietitians, pharmacists are the third largest group of health professionals who
      hold the CDE credential. The growing number of CDE pharmacists highlights the
      increasing involvement of pharmacists in diabetes care. What remains unknown is
      the specific settings in which pharmacist CDEs practice. Methods A cross
      sectional, nationwide electronic survey was sent to all CDE pharmacists in the
      United States. Questions regarding demographics, practice setting
      characteristics, certification information, and common diabetes-related
      counseling topics were asked of all respondents. Survey items also sought to
      determine pharmacists' perceptions of the benefits and barriers to obtaining the
      CDE credential. The questions were dichotomous, Likert-scale response, or open
      ended. Results A total of 462 survey responses were included in the analysis for
      a response rate of (462/1275) 36.2%. Respondents identified hospital or health
      system as the most common practice setting (n = 311), followed by academia (n =
      100), community (n = 81), managed care (n = 44), and other settings. Conclusions
      Study findings provide important data that describe where CDE pharmacists are
      practicing to provide diabetes education. The continued steady growth of CDE
      pharmacists suggests a consistent increase of pharmacists practicing diabetes
      education. Diabetes educators should recognize that CDE pharmacists practice in a
      variety of different settings.

PMID- 29577817
TI  - Carbon/FexOy magnetic composites obtained from PET and red mud residues:
      paracetamol and dye oxidation.
AB  - Composite materials from PET and red mud (RM) wastes were used as catalysts for
      environmental application such as the wastewater treatment. The PET-RM catalysts
      were obtained by a mechanical mixture of the residues followed by thermal
      treatment under an N2 atmosphere (300 degrees C/1 h). An additional activation of
      the composites with CO2 was investigated (at 800-900 degrees C) to reduce the red
      mud basicity. The CO2 activation affected the composites surface area and reduced
      their carbon content. XRD revealed that the haematite (alpha-Fe2O3) and
      maghemite/magnetite are the main iron oxides present in the composites. Mossbauer
      characterization indicated the formation of reduced iron species (Fe2+), highly
      reactive, after the composites heat treatment. The materials were very active
      catalysts for methylene blue (MB) and paracetamol (PRC) removal from aqueous
      solution. The catalytic activity revealed to be dependent on the surface area and
      mainly of the presence of reduced iron species in the catalysts. The MB removal
      reached 97% for both PET-RM 800/2 h and PET-RM 800/5 h, after 1 h of reaction. In
      the case of PRC, the highest removal was also obtained for PET-RM 800/2 h and PET
      RM 800/5 h, of ~25% and 40%, respectively. The contaminants removal mechanism
      likely occurred through combined adsorption and Fenton-like oxidation processes.

PMID- 29577818
TI  - Vietnamese American Women's Beliefs and Perceptions About Breast Cancer and
      Breast Cancer Screening: A Community-Based Participatory Study.
AB  - INTRODUCTION: Although breast cancer (BC) rates are declining in White non
      Hispanic American women, they are increasing among Vietnamese American women
      (VAW) at 1.2% (95% confidence interval [0.1, 2.2]) per year. BC screening rates
      (64%) are below the national rates (81.1%). This article explores VAW's beliefs
      about BC and screening. METHOD: Using community-based participatory qualitative
      descriptive methods, 40 VAW were recruited from Oregon, and four focus groups
      were conducted. A directed content analysis was used. RESULTS: Main themes were
      as follows: deferred to a health care provider or relying on self-detection and
      symptoms; fear of BC versus fear of procedural pain; limited knowledge;
      motivation by observing others' journey in BC death or survivorship; body image
      concern; "living carefree," "good fortune-having good health"; and coverage for a
      mammogram expense means health care access. DISCUSSION: Tailored interventions
      should address mammogram knowledge, fear, erroneous information, body image, fate
      and luck, and promoting access.

PMID- 29577819
TI  - Comparison of the efficacy of parenteral and oral treatment for nutritional
      vitamin B12 deficiency in children.
AB  - OBJECTIVE: Although, oral replacement for vitamin B12 deficiency has been proved
      to be effective in adults, it is mainly treated with parenteral therapy. There
      are only few studies on oral replacement therapy of vitamin B12 with children.
      Therefore, we aimed to compare the efficacy of oral treatment with intramuscular
      vitamin B12 injections in pediatric population. METHODS: Children with serum
      cobalamin concentrations less than 300 pg/mL, were treated either with the
      parenteral therapy or with oral vitamin B12. The primary and secondary outcomes
      of the study were the normalization of serum vitamin B12 and hemoglobin at first
      month, respectively. RESULTS: Post-treatment vitamin B12 values were
      significantly higher than pre-treatment values (p-value <.001). Vitamin B12
      increased from 183.5 +/- 47 pg/mL to 482 +/- 318.9 pg/mL in the oral and from
      175.5 +/- 42.5 pg/mL to 838 +/- 547 pg/mL in the parenteral treatment arm (p
      value <.001). Before treatment, 82 children had anemia according to age and
      gender. After treatment, 14/41 and 8/41 patients still had anemia at the first
      month of treatment in the parenteral and oral arms, respectively. The number of
      patients who still have anemia at the end of the 1st month of treatment did not
      significantly changed in the parenteral and oral treatment groups (p-value =
      .44). CONCLUSIONS: In this study, both oral and parenteral formulations were
      shown to be effective in normalizing vitamin B12 levels. We suggest that oral
      formulations may be considered to be safe as a first line treatment for vitamin
      B12 deficiency in children.

PMID- 29577820
TI  - Risk factor profile in patients with stroke at a young age.
AB  - Background The distribution of risk factors for stroke is related to gender and
      age. The main objective of study was to determine the type and frequency of
      stroke risk factors in patients with first-in-life stroke before the age of 50.
      Methods Our study included patients under the age of 50 with first-in-life
      stroke. The following data obtained from all participants were analyzed: a
      neuroimaging of the head, wide panel of blood tests, electrocardiogram,
      transesophageal echocardiography, ultrasound of the carotid/cerebral arteries. 24
      hour ECG monitoring and angio-MRI of head were performed in most patients.
      Results One hundred and eighty-four patients were qualified into the study; mean
      age - 39 years (female 45%). The female gender was significantly more often
      associated with diabetes, carotid/cerebral artery stenosis, myocardial
      infarction, cardiomyopathy and risk factors associated with lifestyle. More than
      half of the patients presented at least two risk stroke factors. The most
      frequent categories of risk factors were related to arteries and metabolic
      diseases. Vascular risk factors were among the most frequent in individual age
      categories. Hereditary stroke-burden was significant in the patient before the
      age of 20.15% of the patients haven't got known stroke risk factor. Conclusions
      Angiopathy is the most common risk factor for stroke at a young age. More than
      half of the patients with stroke at a young age have at least two independent
      risk factors for stroke. In the first two decades of life, the most frequent risk
      factors for stroke are heart diseases; arterial diseases play a dominant role in
      the consecutive three decades.

PMID- 29577821
TI  - A patient's view on the location of the temporomandibular joint.
AB  - Objective A survey was held to establish whether laypeople knew the location of
      their temporomandibular joint. Methods A sample of 61 participants, visiting
      their dental office for a routine check-up, was given a three-question survey of
      whether they knew the location of their temporomandibular joint and could point
      to this location. Results Thirty-eight participants answered the question
      affirmatively. Only 13 pointed to the correct location. Of these, six
      participants received consultation for TMD in the past, three participants were
      healthcare providers, and four participants actually had knowledge of the exact
      location. Out of 23 participants who did not know the location, one accidently
      designated the correct position. Conclusion The location of the temporomandibular
      joint is not a well-known site for many patients. In the presence of orofacial
      pain, it seems advisable to let the patient designate and record the site of the
      pain on a drawing on the patient chart.

PMID- 29577822
TI  - Psychocardiological disorder and brain serotonin after comorbid myocardial
      infarction and depression: an experimental study.
AB  - Objectives We investigated whether trimetazidine pretreatment can regulate
      central and peripheral serotonin (5-HT) in rats of myocardial infarction (MI)
      combined with depression. Methods Forty rats were randomly assigned to a sham
      operation group (n = 10) and a disease model group (n = 30). The sham operation
      group was pretreated with normal saline for 4 weeks. The disease model group was
      randomly assigned further into a negative control subgroup, a positive control
      subgroup, and a treatment subgroup - the groups received saline, sertraline, and
      trimetazidine pretreatment, respectively, for 4 weeks, then the rats were
      subjected to MI combined with depression. 5-HT concentrations in the serum,
      platelet lysate, and cerebral cortex lysate were analyzed with ELISA. Results The
      levels of serum 5-HT and platelet 5-HT were significantly lower in negative
      control subgroup than the sham operation group (P < 0.05), but there was no
      significant difference in brain 5-HT (P > 0.05). Compared with the negative
      control subgroup, the levels of serum 5-HT and platelet 5-HT in the positive
      control subgroup and treatment subgroup were significantly higher (P < 0.05). The
      levels of 5-HT in brain of the positive control subgroup and treatment subgroup
      were significantly lower than those in the negative control subgroup (P < 0.05).
      Conclusions Trimetazidine pretreatment can increase serum and platelet 5-HT
      levels in rats with MI and depression and decrease 5-HT levels in brain tissue.
      This regulatory effect on central and peripheral 5-HT suggests a role for
      trimetazidine in the treatment of psychocardiological diseases.

PMID- 29577823
TI  - Testing the Predictive Validity of the Hendrich II Fall Risk Model.
AB  - Cumulative data on patient fall risk have been compiled in electronic medical
      records systems, and it is possible to test the validity of fall-risk assessment
      tools using these data between the times of admission and occurrence of a fall.
      The Hendrich II Fall Risk Model scores assessed during three time points of
      hospital stays were extracted and used for testing the predictive validity: (a)
      upon admission, (b) when the maximum fall-risk score from admission to falling or
      discharge, and (c) immediately before falling or discharge. Predictive validity
      was examined using seven predictive indicators. In addition, logistic regression
      analysis was used to identify factors that significantly affect the occurrence of
      a fall. Among the different time points, the maximum fall-risk score assessed
      between admission and falling or discharge showed the best predictive
      performance. Confusion or disorientation and having a poor ability to rise from a
      sitting position were significant risk factors for a fall.

PMID- 29577824
TI  - Cavitating Leukoencephalopathy With Posterior Predominance Caused by a Deletion
      in the APOPT1 Gene in an Indian Boy.
AB  - A 5-year-old Indian boy presented with subacute onset regression of milestones
      associated with seizures and spasticity. The symptoms started after an attack of
      measles. The magnetic resonance imaging (MRI) of the brain showed cavitating
      leukodystrophy with posterior predominance. Molecular analysis of the APOPT1
      gene, a recently described gene associated with mitochondrial leukodystrophy,
      showed the patient to be homozygous for a 12.82-kilobase deletion, including
      coding exon 3. Deletion of exon 3 produces a frameshift, predicting the
      translation of a truncated protein (p.Glu121Valfs*4). The patient was started on
      mitochondrial cocktail regimen of thiamine, riboflavin, coenzyme Q and carnitine.
      Although he initially showed some improvement, he died 6 months after the onset
      of his illness.

PMID- 29577825
TI  - Trajectories of positive aspects of caregiving among family caregivers of stroke
      survivors: the differential impact of stroke-survivor disability.
AB  - Objective To delineate positive aspects of caregiving trajectories among family
      caregivers of stroke-survivors and determine the impact of stroke-survivor
      disability, a time-varying factor, on the delineated trajectories. Methods In a
      longitudinal study, family caregivers of 173 stroke-survivors in Singapore were
      administered the Positive Aspects of Caregiving scale (PAC scale) thrice
      (baseline/3 months/6 months). Group-based trajectory modeling delineated positive
      aspects of caregiving trajectories and identified the impact of stroke-survivor
      disability on the trajectories. Results Two distinct positive aspects of
      caregiving trajectories, Persistently Low and Persistently High were delineated.
      Increase in stroke-survivor disability was associated with a significant downward
      shift (reduction in positive aspects of caregiving) of the Persistently Low
      trajectory and a significant upward shift (increase in positive aspects of
      caregiving) of the Persistently High trajectory. Older caregivers were more
      likely to follow the Persistently High trajectory. Conclusions Care professionals
      should be mindful of the heterogeneity in the longitudinal pattern of positive
      feelings resulting from care provision among family caregivers of stroke
      survivors, and the differential impact of stroke-survivor disability on the
      pattern of positive feelings. Younger caregivers as well as family caregivers who
      have low positive feelings at the start of their caregiver journey and experience
      worsening functional disability of their care recipient (stroke-survivor) require
      greater attention and support.

PMID- 29577826
TI  - Pain, Fear of Falling, and Functional Performance Among Nursing Home Residents: A
      Longitudinal Study.
AB  - The aim of this study was to analyze the impact of being pain-affected and fear
      of falling on functional performance among nursing home residents,
      longitudinally. We used 6-month follow-up data from a cluster-randomized trial of
      12 nursing homes (cluster level) with 239 nursing home residents at baseline
      (mean age, 95% confidence interval [CI] = 83.04 [81.40, 84.69], 70% women). The
      longitudinal analysis provided data on pain, fear of falling, functional
      mobility, and activities of daily living (individual level). The data revealed a
      trend indicating that pain-relieved nursing home residents showed better
      functional mobility over time. The results on fear of falling demonstrate obvious
      differences in the functional performance of nursing home residents cross
      sectionally but not longitudinally. Nevertheless, the results underline the
      importance of an effective pain treatment to prevent decline in functional
      mobility among nursing home residents. Further longitudinal surveys are needed to
      verify the findings on functional performance.

PMID- 29577827
TI  - The transfer of strength and power into the stroke biomechanics of young swimmers
      over a 34-week period.
AB  - The purpose of this study was to learn the interplay between dry-land strength
      and conditioning, and stroke biomechanics in young swimmers, during a 34-week
      training programme. Twenty-seven swimmers (overall: 13.33 +/- 0.85 years old; 11
      boys: 13.5 +/- 0.75 years old; 16 girls: 13.2 +/- 0.92 years old) competing at
      regional- and national-level competitions were evaluated. The swimmers were
      submitted to a specific in-water and dry-land strength training over 34 weeks
      (and evaluated at three time points: pre-, mid-, and post-test; M1, M2, and M3,
      respectively). The 100-m freestyle performance was chosen as the main outcome
      (i.e. dependent variable). The arm span (AS; anthropometrics), throwing velocity
      (TV; strength), stroke length (SL), and stroke frequency (SF; kinematics) were
      selected as independent variables. There was a performance enhancement over time
      (M1 vs. M3: 68.72 +/- 5.57 s, 66.23 +/- 5.23 s; Delta = -3.77%; 95% CI: -3.98;
      3.56) and an overall improvement of the remaining variables. At M1 and M2, all
      links between variables presented significant effects (p < .001), except the TV
      SL and the TV-SF path. At M3, all links between variables presented significant
      effects (p <= .05). Between M1 and M3, the direct effect of the TV to the stroke
      biomechanics parameters (SL and SF) increased. The model predicted 89%, 88%, and
      92% of the performance at M1, M2, and M3, respectively, with a reasonable
      adjustment (i.e. goodness-of-fit M1: chi2/df = 3.82; M2: chi2/df = 3.08; M3:
      chi2/df = 4.94). These findings show that strength and conditioning parameters
      have a direct effect on the stroke biomechanics, and the latter one on the
      swimming performance.

PMID- 29577828
TI  - Restless legs syndrome in Multiple Sclerosis patients: a contributing factor for
      fatigue, impaired functional capacity, and diminished health-related quality of
      life.
AB  - Objectives Restless legs syndrome (RLS) symptoms are common in Multiple Sclerosis
      (MS) patients. The aim of the current study was to examine for the first time
      whether RLS could affect the functional capacity and various contributing
      parameters related to quality of life and fatigue in MS patients. Methods
      According to their RLS status, 50 relapsing-remitting MS patients were divided
      into the RLS (n = 10) and non-RLS groups (n = 40). Specific questionnaires were
      used in order to assess the health-related quality of life (HRQoL), fatigue
      levels, sleep quality, daily sleepiness, and depression symptoms of the patients.
      Functional capacity was examined using a battery of functional tests. Total body
      and visceral fat levels were assessed via bioelectrical impedance analyzers.
      Results Sleep quality, depression, fatigue, and HRQoL levels were found to be
      significantly worse in the patients with RLS compared to their free-RLS
      counterparts (P < 0.05). In addition, patients with RLS were found to exhibit
      further impairments in their performance in various functional tests related
      mainly with strength levels of lower extremities (P < 0.05). Finally, the
      patients with RLS were found to have significantly higher both total and trunk
      fat levels compared to patients without RLS (P < 0.05). A strong correlation was
      observed between the severity of RLS symptoms, sleep quality, fatigue, and QoL
      levels. Discussion It seems that RLS contributes even further to impairments on
      sleep quality, fatigue, functional capacity, and therefore HRQoL levels in
      relapsing-remitting MS patients, whilst for the first time a link between high
      fat levels has been revealed.

PMID- 29577829
TI  - Single-Docking Full Robotic Surgery for Rectal Cancer: A Single-Center
      Experience.
AB  - PURPOSE: Robotic surgery has gradually gained importance in the treatment of
      rectal cancer. However, recent studies have not shown any advantages when
      compared with laparoscopy. The objective of this study is to report a single
      surgeon's experience in robotic rectal surgery focusing on short-term and long
      term outcomes. METHODS: Sixty consecutive robotic rectal resections for
      adenocarcinoma, over a 4-year period, were retrospectively reviewed. Patients'
      characteristics and perioperative outcomes were analyzed. Oncological outcomes
      and surgical resection quality as well as overall and disease-free survival were
      also assessed. RESULTS: Thirty patients out of 60 (50%) underwent neoadjuvant
      therapy. Anterior rectal resection was performed in 52 cases (86.7%), and
      abdominoperineal resection was done in 8 cases (13.3%). Mean operative time was
      283 (+/-68.6) minutes. The conversion rate was 5% (3 patients). Postoperative
      complications occurred in 10 cases (16.7%), and reoperation was required in 1
      case (1.7%). Mean hospital stay was 9 days, while 30-day mortality was 1.7% (1
      patients). The histopathological analysis reported a negative circumferential
      radial margin and distal margins in 100% of cases with a complete or near
      complete total mesorectal excision in 98.3% of patients. Mean follow-up was 32.8
      months with a recurrence rate of 3.4% (2 patients). Overall survival and disease
      free survival were 94% and 87%, respectively. CONCLUSIONS: Robotic surgery for
      rectal cancer proves to be safe and feasible when performed by highly skilled
      surgeons. It offers acceptable perioperative outcomes with a conversion rate
      notably lower than with the laparoscopic approach. Adequate pathological results
      and long-term oncological outcomes were also obtained.

PMID- 29577830
TI  - Robotic Colorectal Resection With and Without the Use of the New Da Vinci Table
      Motion: A Case-Matched Study.
AB  - BACKGROUND: The da Vinci Table Motion (dVTM) is a new device that enables
      patients to be repositioned with instruments in place within the abdomen, and
      without undocking the robot. The present study was designed to compare operative
      and short-term outcomes of patients undergoing colorectal cancer surgery with the
      da Vinci Xi system, with or without use of the dVTM. METHODS: Ten patients
      underwent robotic colorectal resection for cancer with the use of dVTM (Xi-dVTM
      group) between May 2015 and October 2015 at our center. The intraoperative and
      short-term clinical outcome were compared, using a case-control methodology
      (propensity scores approach to create 1:2 matched pairs), with a similar group of
      patients who underwent robotic colorectal surgery for cancer without the use of
      the dVTM device (Xi-only group). RESULTS: Overall robotic operative time was
      shorter in the Xi-dVTM group ( P = .04). Operations were executed fully robotic
      in all Xi-dVTM cases, while 2 cases of the Xi-only group required conversion to
      open surgery because of bulky tumors and difficult exposure. Postoperative
      medical complications were higher in the Xi-only group ( P = .024). CONCLUSIONS:
      In this preliminary experience, the use of the new dVTM with the da Vinci Xi in
      colorectal surgery, by overcoming the limitations of the fixed positions of the
      patient, enhanced the workflow and resulted in improved exposure of the operative
      field. Further studies with a greater number of patients are needed to confirm
      these benefits of the dVTM-da Vinci Xi robotically assisted colorectal surgery.

PMID- 29577831
TI  - The Use of Barbed Suture for Intracorporeal Mechanical Anastomosis During a
      Totally Laparoscopic Right Colectomy: Is It Safe? A Retrospective Nonrandomized
      Comparative Multicenter Study.
AB  - BACKGROUND: A totally laparoscopic right colectomy could be perceived as a more
      challenging procedure over a laparoscopic-assisted right colectomy owing to the
      difficulty of intracorporeal anastomosis and the closure of the enterotomy. The
      aim of this study is to evaluate the safety and efficacy of the barbed auto
      locking absorbable suture for the closure of an anastomotic stapler-access
      enterotomy during a totally laparoscopic right colectomy. METHODS: From January
      2010 to April 2016, data from patients who had undergone a laparoscopic right
      colectomy in 2 different departments of 2 institutions (the Department of General
      and Minimally Invasive Surgery, San Camillo Hospital in Trento and the Department
      of Surgical Specialties and Nephrology, University Federico II in Naples) were
      retrospectively analyzed. We compared the data of patients in whom the stapler
      access enterotomy was closed through a conventional absorbable suture (Group A),
      with the data of patients in whom a stapler-access enterotomy was closed through
      a V-Loc 180 suture (Group B). Biometric features and intraoperative and
      postoperative data were collected and analyzed. RESULTS: The 2 groups (Group A:
      40 patients; Group B: 40 patients) were comparable for biometric features and
      postoperative outcomes. The anastomosing time was lower in Group B. A
      statistically significant difference was noted in the mean operative time between
      Groups A and B (Group A = 134.92 +/- 34.17; Group B = 120.92 +/- 23.27, P =
      .035). Only one anastomotic leakage per group was recorded, each treated with an
      anastomosis redo. During the reoperations, we find in both groups an intact
      stapler-access enterotomy. CONCLUSION: On retrospective analysis, barbed suture
      appears to be safe and efficient for closure of the stapler-access enterotomy
      during totally laparoscopic right colectomy.

PMID- 29577832
TI  - The Need for Accurate Records.
AB  - Dear AfPP I have recently obtained a senior post in a hospital that is in a
      different part of the UK in relation to where I have always worked. I have become
      aware of differing practices, many of which are improving patient care. However,
      I am concerned that in this perioperative environment, there is no permanent
      record of items used during each case. The only records of the items used in any
      one case are those that are recorded on the swab board and the signatures of the
      staff who undertake the final count in the theatre register. In some of my
      previous jobs, we have recorded the count on a separate sheet that was then filed
      in the patients' notes by the scrub practitioner of the case, thus providing a
      permanent record of the count in the patients' notes. Can AfPP advise on whether
      a record in the patients' notes is necessary? Concerned from County Armagh.

PMID- 29577834
TI  - "Do You Want to Go Forward or Do You Want to Go Under?" Men's Mental Health in
      and Out of Prison.
AB  - More than 11 million people are currently imprisoned worldwide, with the vast
      majority of incarcerated individuals being male. Hypermasculine environments in
      prison are often tied to men's health risks, and gathering information about
      mental health is fundamental to improving prison as well as community services.
      The purpose of the current study was to describe the connections between
      masculinities and men's mental health among prisoners transitioning into and out
      of a Canadian federal correctional facility. Two focus groups were conducted with
      a total of 18 men who had recently been released from a federal correctional
      facility. The focus group interviews were analyzed to inductively derive patterns
      pertaining to men's mental health challenges and resiliencies "on the inside" and
      "on the outside." Participant's challenges in prison related to heightened
      stresses associated with being incarcerated and the negative impact on
      preexisting mental illness including imposed changes to treatment regimens. Men's
      resiliencies included relinquishing aggression and connecting to learn from other
      men "on the inside." Mental health challenges "on the outside" included a lack of
      work skills and finances which increased the barriers that many men experienced
      when trying to access community-based mental health services. Mental health
      resiliencies employed by participants "on the outside" included self-monitoring
      and management to reduce negative thoughts, avoiding substance use and attaining
      adequate exercise and sleep. The current study findings offer practice and policy
      guidance to advance the well-being of this vulnerable subgroup of men in as well
      as out of prison.

PMID- 29577833
TI  - Association Between Nonalcoholic Fatty Liver Disease and Severe Male Reproductive
      Organ Impairment (Germinal Epithelial Loss): Study on a Mouse Model and on Human
      Patients.
AB  - Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic
      fatty liver disease (NAFLD) is a multisystemic disease that affects different
      organs, but its effect on the testes is unknown. A study analyzing germ cell
      involvement on BALB/c mice was carried out. A parallel comparative study was
      conducted that investigated alterations in the germinal epithelium of male humans
      that died from an unrelated acute event. The complete medical histories and
      histologic samples of the thoracic aorta, liver tissue, and testicular tissue
      from the deceased subjects were collected. The degree of germinal epithelial loss
      (DGEL) was evaluated and the clinical and histologic data were compared between
      individuals with and without NAFLD. The only metabolic or morphologic variable
      that caused a significant difference in the DGEL, in both the animal model and
      humans, was the presence of liver steatosis. The percentage of steatosis was also
      correlated with the percentage of the DGEL. In humans, steatosis (greater than
      20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95%
      CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS
      components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD
      was a strongly associated factor implicated in severe DGEL, as well as the testis
      was identified as a probable target organ for damage caused by the disease. This
      finding could result in the search for new approach strategies in the management
      of men with fertility problems. Further studies are required to confirm these
      results.

PMID- 29577835
TI  - Hispanic Young Males' Mental Health From Adolescence Through the Transition to
      Fatherhood.
AB  - The objective of the current study was to examine the associations between the
      transition to fatherhood and depressive symptoms scores among Hispanic men. Using
      the sample of Hispanic men included in the National Longitudinal Study of
      Adolescent to Adult Health, depressive symptom scores were examined from 1994 to
      2008. A "fatherhood-year" data set was created that included the men's Center for
      Epidemiologic Studies Depression Scale (CES-D) scores as well as residency status
      with the child. By regressing age-adjusted standardized depressive symptom
      scores, associations between mental health scores of Hispanic men and their
      transition to fatherhood were identified. Among the 1,715 Hispanic men, resident
      ( n = 502) and nonresident ( n = 99) Hispanic fathers reported an increase in
      depressive symptom scores (CES-D) during the first 5 years after entrance into
      fatherhood (beta = 0.150, 95% CI [0.062, 0.239] and beta = 0.153, 95% CI [0.034,
      0.271], respectively) compared to non-fathers ( n = 1,114), representing an
      increase of 10% for resident fathers and a 15% for nonresident fathers. Hispanic
      non-fathers reported a decrease in depressive symptom scores (CES-D) during
      parallel ages. Hispanic fathers, regardless of residency status, reported
      increased depressive symptoms in the first 5 years after the transition into
      fatherhood, a period critical in child development.

PMID- 29577836
TI  - "Boy Crisis" or "Girl Risk"? The Gender Difference in Nonsuicidal Self-Injurious
      Behavior Among Middle-School Students in China and its Relationship to Gender
      Role Conflict and Violent Experiences.
AB  - PURPOSE: We attempted to test if there were gender differences in nonsuicidal
      self-injurious (NSSI) behaviors among Chinese middle-school students, and analyze
      the impact of gender role conflict and violent experiences on these behaviors
      among middle-school students of different genders. METHOD: Based on the survey
      data from seven middle schools in Xi'an region of China, the gender difference in
      NSSI behaviors and its associated factors were analyzed in this study. RESULTS:
      There was no significant gender difference in NSSI behaviors among middle-school
      students; however, female middle-school students were more likely to experience
      gender role conflicts while male students were more likely to experience all
      kinds of violence earlier. Gender role conflicts and violent experiences can
      explain the prevalence of NSSI behaviors by gender, to some extent. CONCLUSIONS:
      The hypothesis on gender patterns of "boy crisis" or "girl risk" on NSSI
      prevalence was not verified; however, a "girl risk" for gender role conflicts and
      a "boy crisis" in violent experiences were found. The gender role conflicts were
      significantly associated with NSSI prevalence among middle-school students to
      some extent; however, this relationship was adjusted by variables of violent
      experiences. The different variables of violent experiences were the important
      predictors of NSSI prevalence among male and female middle-school students with
      specific contents varying across genders.

PMID- 29577837
TI  - 2016 Survey of State-Level Health Resources for Men and Boys: Identification of
      an Inadvertent and Remediable Service and Health Disparity.
AB  - This survey evaluated resources available to men and boys at the state level
      including state public health departments (SPHDs), other state agencies, and
      governor's offices. Most of the resources and programs are found in the SPHDs and
      these administer state-initiated and federally funded health programs to provide
      services and protection to a broad range of populations; however, many men's
      health advocates believe that SPHDs have failed to create equivalent services for
      men and boys, inadvertently creating a health disparity. Men's Health Network
      conducts a survey of state resources, including those found in SPHDs, every 2
      years to identify resources available for men and women, determine the extent of
      any disparity, and establish a relationship with SPHD officials. Data were
      obtained from all 50 states and Washington, D.C. An analysis of the 2016 survey
      data indicates that there are few resources allocated and a lack of readily
      available information on health and preventive care created specifically for men
      and boys. The data observed that most health information intended for men and
      boys was scarce among states or oftentimes included on websites that primarily
      focused on women's health. A potential result of this is a loss of engagement
      with appropriate health-care providers due to a lack of information. This study
      continues to validate the disparity between health outcomes for women and men. It
      continues to highlight the need for better resource allocation, outreach, and
      health programs specifically tailored to men and boys in order to improve overall
      community well-being.

PMID- 29577838
TI  - Effort-Reward Imbalance and Work Productivity Among Hotel Housekeeping Employees:
      A Pilot Study.
AB  - This study explored the relationship between effort-reward imbalance (ERI) at
      work and work productivity among hotel housekeepers. A community-based approach
      was used to recruit 23 hotel housekeepers who completed the ERI and Work
      Performance Questionnaires. Work productivity was determined by combining self
      report absenteeism and presenteeism. More than 40% of the participants reported
      high ERI (ERI >1). Also, 59.1% reported low work productivity. Interestingly,
      despite the individualized high reports of ERI and low work productivity,
      correlation analysis showed that high ERI was correlated with high presenteeism
      and work productivity as a whole. This is the first study to explore work
      productivity among this worker group. Despite the small sample size and the cross
      sectional nature of the study, this study points to the need for organization
      based interventions to not only improve employee health but also their work
      productivity.

PMID- 29577839
TI  - Single-sided deaf tactical unit officer treated with cochlear implantation.
AB  - OBJECTIVES: To demonstrate the efficacy of cochlear implantation for management
      of a severe single-sided deaf tactical unit officer. Showing that hearing
      improvement provided by cochlear implantation was sufficient for him to return to
      work as a police tactical officer. METHODS: Case report. RESULTS: A 43 years-old
      man working as a tactical unit officer suffered from a work-related severe single
      sided hearing loss. He tried unsuccessfully many types of hearing aids including
      a contralateral routing of sound (CROS) system and a bone conduction hearing aid
      with a headband. He was finally treated with cochlear implantation which provided
      enough localization and hearing abilities for a complete return to work as a
      tactical unit officer. DISCUSSION: This case report demonstrates that cochlear
      implantation was very successful for a patient suffering from severe single-sided
      hearing loss. The current literature demonstrates benefits from cochlear implant
      over CROS and osseointegrated devices in unilateral hearing loss. Nevertheless,
      literature does not report any case of patient suffering from single-sided
      deafness that received a cochlear implant and a complete bilateral hearing
      rehabilitation that allowed him to return to work as a police tactical officer.
      CONCLUSION: Cochlear implantation was the only effective treatment to provide our
      patient enough localization and hearing abilities for a complete return to work
      as a police tactical officer. As no consensus has been established about
      selection criteria for cochlear implantation in single-sided deafness, we suggest
      that the patient's occupation should be considered when reviewing his candidacy
      for cochlear implantation.

PMID- 29577840
TI  - The Relevance of Victimization Experiences for Predicting the Development of
      Threat Symptoms During Adolescence and Early Adulthood.
AB  - The "threat" portion of the threat/control override symptom constellation is
      characterized by the belief by an individual that others seek to do them harm.
      There has yet to be an examination of the link between perceived threat
      symptomatology and the experience of victimization, despite the fact that both
      constructs are linked to the perpetration of violent behavior. Furthermore, there
      has yet to be research which examines the heterogeneity in developmental patterns
      of threat symptomatology. The present research utilized the Pathways to
      Desistance data to model the developmental heterogeneity in perceived threat
      symptomatology across adolescence and early adulthood using group-based
      trajectory modeling. A series of multinomial logistic regression models were then
      estimated to examine the relevance of victimization experiences for predicting
      trajectory group assignment. A five-group model of development during adolescence
      and early adulthood best fit the threat symptom data. Victimization experienced
      prior to age 16 predicted assignment to all groups in the model characterized by
      presentation of threat symptoms at some point during the study. Victimization
      experienced between ages 16 and 23 predicted assignment to the High Chronic group
      and marginally predicted assignment to the Accelerating group. These results
      indicate that victimization does indeed predict the presentation of perceived
      threat symptomatology. This indicates that presentation of threat symptoms may be
      indicative of a history of victimization. Proper screening of those presenting
      threat symptoms may help to better orient treatment plans for modalities centered
      on victimization experiences. Future research should investigate the possibility
      that threat symptoms mediate the relationship between victimization and violent
      behavior.

PMID- 29577841
TI  - Exploring the Potential Campus-Level Impact of Online Universal Sexual Assault
      Prevention Education.
AB  - Campus sexual assault is a long-standing challenge and continues to be a severe
      problem for American higher education. The present study examines the short-term
      impact of a widely utilized sexual violence prevention course for matriculating
      college students as a population-level prevention approach. The course focuses on
      correcting misperceptions of normative behavior, increasing students' likelihood
      to intervene in disconcerting situations, and encouraging empathy and support for
      victims. Participants were 167,424 first-year college students from 80 four-year
      institutions who completed preintervention and postintervention surveys to assess
      changes in composite factor scores derived from 20 attitudinal, self-efficacy,
      and behavioral intention items. Employing the composite factor scores as
      dependent variables, individual ANOVAs were run for each of the institutions to
      test whether there were significant increases in mean factor scores. High
      percentages of institutions saw statistically significant increases ( p < .05) in
      self-reported ability and intention to intervene to prevent sexual assault and
      relationship violence (98%), empathy and support for victims (84%), and corrected
      perceptions of social norms (75%). Fewer schools saw significant reductions in
      endorsement of sexual assault myths (34%). These findings suggest that when
      implemented as a population-level intervention for all first-year college
      students, the prevention course can foster accurate perceptions of positive
      social norms, increase empathy and support for victims, and increase students'
      stated ability and intention to intervene.

PMID- 29577842
TI  - Sexual Violence Among College Students Attending a Nonresidential Campus.
AB  - Using the empirical powers of theories of intersectionality, the study
      investigates the association between students' demographics (such as gender
      identity, race, ethnicity, age, and socioeconomic status) and sexual violence
      victimization. An anonymous survey was employed to collect data from a cluster
      random sample of 966 students attending face-to-face courses at a midsize urban
      nonresidential campus. The empirical findings suggest that being older and female
      are the only statistically significant factors in the analysis. As the first
      attempt to focus on students attending nonresidential programs in the United
      States, the study presents implications for policy and program implementation to
      include issues pertinent to students' diversity to better respond to students'
      risk of victimization.

PMID- 29577843
TI  - Contributions to Depressed Affect in Latina Women: Examining the Effectiveness of
      the Moms' Empowerment Program.
AB  - Intimate partner violence (IPV) is a significant social and public health problem
      that includes physical violence, sexual violence, threats of physical or sexual
      violence, stalking, and psychological aggression by an intimate partner.
      Estimates suggest that 35% of Latinas living in the United States experience IPV
      in their lifetime, with known severe negative outcomes. One mental health
      consequence of concern is depression, which disproportionately affects IPV
      exposed Latinas. The present study tested the effectiveness of the Moms'
      Empowerment Program (MEP), a culturally adapted intervention to reduce depressive
      symptoms among IPV-exposed Spanish-speaking Latina mothers. Additional
      psychosocial predictors of levels of depressed affect over time are examined,
      including levels of post-traumatic stress, IPV exposure, positive parenting,
      parental acceptance of children's negative emotions, and maternal employment.
      Participants ( N = 72) were assigned to a treatment or a wait-list comparison
      condition, and those in the treatment group completed a 10-week group
      intervention addressing the unique problems associated with IPV exposure, mental
      health, and parenting among Spanish-speaking Latinas. Results of multilevel
      modeling revealed that participation in the MEP was associated with significant
      reductions in depressed affect. Lower levels of post-traumatic stress and higher
      levels of positive parenting, maternal acceptance of children's negative
      emotions, and maternal employment predicted lower levels of depressed affect. The
      amount of total IPV exposure was not significantly associated with the extent of
      depressed affect. The MEP represents a culturally tailored, evidence-based
      intervention to reduce depressed affect among Spanish-speaking Latinas. The
      clinical implications of the additional predictors of levels of depressed affect
      are discussed.

PMID- 29577844
TI  - Factors Affecting Sexual History Taking in a Health Center Serving Homeless
      Persons.
AB  - Low rates of documentation of sexual histories have been reported and research on
      sexual history taking (SHT) has focused on the content of, barriers to
      collecting, and interventions to improve documentation of sexual histories.
      Absent from this literature is an understanding of the contextual factors
      affecting SHT. To address this gap, a focused ethnography of one health center
      was conducted. Data were collected through observations of health care encounters
      and interviews with health care providers (HCPs). No SHT was observed and this
      was likely influenced by patients' characteristics, communication between
      patients and HCPs, the prioritization of patients' basic needs, and time
      constraints imposed upon encounters. Given that the health center studied serves
      patients experiencing homelessness, behavioral health concerns, and opioid use
      disorder, findings illuminate areas for future inquiry into a patient population
      affected by social as well as physiologic determinants of health and potentially
      at high risk for adverse sexual health outcomes.

PMID- 29577845
TI  - The Dominant Obesity Discourse Versus Children's Conceptualizations of Health: A
      Comparison Through Dialogue and Drawings.
AB  - The emphasis on childhood obesity reduction has been attributed to the dominant
      obesity discourse. However, some researchers argue that this discourse may be
      ineffective and even harmful for children. From a post-structuralist perspective,
      the dominant obesity discourse has the power to shape children's subjectivities,
      though subjectivities may also be influenced by personal experiences and other
      knowledge about bodies and health. There is limited research which explores how
      children's conceptualizations of health are informed by the dominant obesity
      discourse. To address this knowledge gap, qualitative data were collected from 8-
      to 11-year-old children ( n = 29) regarding their conceptualizations of health,
      healthy bodies, and health practices. Results suggest that children's
      conceptualizations reflected arguments embedded within the dominant obesity
      discourse, but at times, also contradicted or deviated from it. Study findings
      can be applied toward children's health promotion programming to offer a more
      holistic and inclusive perspective on health and well-being.

PMID- 29577846
TI  - "Like Every Normal Person?!" The Paradoxical Effect of Aging With Schizophrenia.
AB  - Studies on aging with schizophrenia have focused mainly on the adversities of
      aging with mental illness. The present study, however, examined the subjective
      experience of well-being among individuals with schizophrenia. Taking a
      phenomenological reflective life-world approach, in-depth, semistructured
      interviews with 18 aging individuals with schizophrenia were thematically
      analyzed. Four main themes emerged: (a) "I love the pills . . . they are very
      helpful": A balanced course of the illness as a basis for well-being in old age;
      (b) "I'm going to have my own exhibition at the museum": Self-fulfillment as
      promoting well-being; (c) "It's just like a family here": Experiencing a sense of
      belonging; and (d) "I live like everyone else": Aging as an opportunity for
      normalization. Alongside hardship, the participants perceived old age as a
      "window of opportunity," enabling the fulfillment of lifelong desires for a
      social life, acceptance, and a satisfying occupation. Implications regarding
      interventions with this unique population are discussed.

PMID- 29577847
TI  - When Your Pregnancy Echoes Your Illness: Transition to Motherhood With
      Inflammatory Bowel Disease.
AB  - Our aim is to provide an understanding of the experience of women with
      inflammatory bowel disease (IBD) who have made the transition to motherhood. A
      total of 22 mothers with IBD were recruited from around the United Kingdom. Semi
      structured interviews were conducted and analyzed using thematic analysis. The
      central concept- Blurred Lines-offers a novel frame for understanding the
      transition to motherhood with IBD through identifying parallels between having
      IBD and becoming, and being, a mother. Parallels clustered into three main
      themes: Need for Readiness, Lifestyle Changes, and Monitoring Personal and
      Physical Development. Hence, women with IBD are in some ways well prepared for
      the challenges of motherhood even though, as a group, they tend to restrict their
      reproductive choices. We recommend health professionals initiate conversations
      about reproduction early and provide a multidisciplinary approach to pregnancy
      and IBD in which women have confidence that their ongoing treatment will be
      integrated successfully with their maternity care.

PMID- 29577848
TI  - Survival, Signaling, and Security: Foster Carers' and Residential Carers'
      Accounts of Self-Harming Practices Among Children and Young People in Care.
AB  - Research on clinicians' interpretations of self-harming practices has shown that
      they can often be negative. To date there has been limited consideration of other
      professionals' narratives, notably those working in social care. This article
      presents focus group and interview data generated with foster carers ( n = 15)
      and residential carers ( n = 15) to explore the symbolic meanings ascribed to
      self-harm among the children and young people they care for. Three repertoires of
      interpretation are presented: survival, which conceives self-harm as a mechanism
      for redefining the identity of "looked-after"; signaling, which understands self
      harm as a communicative tool for the expression of emotion; and security, which
      sees self-harming practices as testing the authenticity and safety of the caring
      relationship. Through their focus on sociocultural narratives, carers position
      themselves as experts on self-harm due to their intimacy with young people's
      social worlds. This construction potentially creates distance from health
      professionals, which is problematic given the current privileging of
      interprofessional working.

PMID- 29577849
TI  - Facial nerve stimulation after cochlear implantation: Our experience in 448 adult
      patients.
AB  - Facial nerve stimulation (FNS) after cochlear implant activation is a well-known
      side effect, with an incidence rate raging between 1% and 14.9%. Some causes of
      deafness have been associated with a higher incidence of this entity, however,
      there is still no consensus regarding its pathophysiological mechanisms. Although
      FNS can be solved with changes in speech processor programming, in some cases
      this can lead to a decrease in performance. The aim of this work was to review
      the epidemiologic, clinical aspects, and performance results in a group of FNS
      after cochlear implantation. It was conducted a retrospective chart review of 448
      adult patients, all implanted between 1985 and 2016. Speech perception tests
      results were statistically analysed, using non-parametric tests. We registered a
      group of 13 patients with FNS, contributing to a prevalence of 2.9%. The causes
      of hearing loss in this group varied between otosclerosis, Meniere's disease,
      head trauma, and idiopathic cause. Six cases were managed by changing the
      programming strategy and the other seven required the deactivation of the
      affected electrodes. Statistical evaluation showed no statistically significant
      difference between the performance results of the groups with and without FNS. In
      this series, the overall incidence of FNS was consistent with the literature. Our
      study supports the current idea that FNS can frequently be eliminated by changing
      programming strategies or deactivating the involved electrodes, without affecting
      the implant's performance.

PMID- 29577850
TI  - A Statistical Approach to Detect Intrinsically Disordered Proteins Associated
      with Uterine Leiomyoma.
AB  - BACKGROUND: Uterine Leiomyoma is mainly widespread non-malignant tumor. Around
      more than 80% woman have these particular tumor among them only 30% of them are
      detected. Integrin-?1 is one of the up regulated biomarkers during tumorigenesis
      which is also associated with structural disordered. Intrinsically disordered
      proteins are one of the types which are dealing with un-structuredness especially
      in tertiary structural orchestration. Around 30% of the human proteins consist of
      intrinsically disordered regions. It is obvious that IDPs should have a
      significant change of functional activities under structure-function paradigm.
      Mostly IDPs are associated with malignancies, neurodegenerative diseases and
      heart diseases. DNA methylation is one Post Transcriptional Modification (PTM)
      techniques where methyl groups are added to nucleotide bases. It is responsible
      to control the functionality of Transcription Factors (TFs). Along with that, the
      structural orchestration is also affected due to PTM. Very few diseases related
      studies are focused on structural disordered along with methylation. OBJECTIVE:
      In this article, our motivation is to establish a relation between uterine
      leiomyoma at differential methylation rate and tissue specific disordered
      proteins. METHOD: In this article, we propose a framework for achieving our
      aforementioned object. We start with two set of data i.e., set of gene
      specifically related with uterine leiomyoma (GUL) and set of tissue specific
      proteins from uniprot (Puterine). Subsequently, 'two sample T-Test' is applied on
      GUL to find differentially methylated sample for uterine leiomyoma (DGUL).
      Comparing the gene transcripts of DGUL with the Puterine , the common biomarkers
      are selected (DPuterine). Thereafter the selected list of proteins is analyzed
      under D2P2 to find percentage disorder rate, number SCOP, number protein families
      and rate PTM. Proteins, with more than 10% of structural disorder rate, consider
      as structurally disordered (PUL disordered). Finally, to validate the listed up
      proteins we perform KEGG pathway and Gene Ontology analysis. RESULTS: Following
      the proposed framework, we start with 2246 proteins from uniprot which are kept
      in Puterine. Under DGUL there are 6555 genes which are differentially methylated
      (p-value <0.05). Only 434 proteins selected from the intersection of DGUL and
      Puterine. Among them only 210 proteins are fallen PUL disordered with more than
      10% structural disorder. Top ten proteins under the range of 100% to 74.2% are
      selected shown in the article. After performing KEGG pathway analysis and Gene
      Ontology analysis, it is found that Q969W3 has no connection with KEGG or GO
      terms. CONCLUSION: After the applying the framework, we get some verified group
      of proteins at different stages of the proposed method. The group of 210
      disordered proteins is verified from the KEGG and GO analysis. As the result is
      verified at satisfactory level then it can be said that the framework is
      successfully analyzed intrinsically disordered proteins, having a connection with
      differential methylation levels for a specific disease.

PMID- 29577851
TI  - Structural and Aggregation Properties of Alpha-Synuclein Linked to Phospholipase
      A2 Action.
AB  - BACKGROUND: Alpha-synuclein is a protein involved in the pathogenesis of
      Parkinson's disease. In vitro observations have shown that specific brain
      enriched polyunsaturated fatty acids, such as arachidonic acid, can give rise to
      a conformational change in alpha-synuclein and ultimately induce its
      fibrillation. Arachidonic acid is released by phospholipase A2 activity and
      clinical observations have shown a link between mutations in PLA2G6, the gene
      responsible for the production of phospholipase A2, and early-onset types of
      parkinsonism. It is unknown how phospholipase A2-driven release of arachidonic
      acid can affect the conformation of alphasynuclein. OBJECTIVE: The main objective
      of this study was to investigate if phospholipase A2-induced release of
      arachidonic acid can induce changes in conformation and aggregation state of
      alpha-synuclein. METHODS: Recombinant human alpha-synuclein was expressed and
      isolated and incubated in the presence of phosphatidylcholine and
      phosphatidylserine (PC/PS) containing liposomes. The release of free fatty acids
      from PC/PS liposomes by bee venom phospholipase A2 was measured with the
      fluorescent probe acrylodated intestinal fatty acid-binding protein (ADIFAB) and
      radioactive labelling by preparing liposomes in the presence of L- 3
      phosphatidylcholine, 1-stearyl-2[1-14C] arachidonoyl. The effect of free fatty
      acid release on the conformation of alpha-synuclein was assayed by far-UV
      circular dichroism and resistance against V8 protease-induced limited
      proteolysis. Aggregation of alpha-synuclein upon exposure to phospholipase A2
      induced action on PC/PS liposomes was measured using thioflavin T fluorescence,
      SDS-PAGE, gel filtration chromatography, and transmission electron microscopy.
      RAW264.7 cells were transiently transfected with human alpha-synuclein and
      release of arachidonic acid was quantified using radiolabeling and liquid
      scintillation counting. RESULTS: Phospholipase A2 is capable of releasing
      arachidonic acid from biomimetic phospholipid membranes. Exposure of alpha
      synuclein to phospholipase A2-induced release of arachidonic acid from PC/PS
      liposomes induces a conformational transition of the protein and leads to partial
      resistance against proteolytic cleavage by V8 protease. Prolonged incubation of
      alpha-synuclein with arachidonic acid, derived from PC/PS liposomes by
      phospholipase A2 leads to aggregate formation. In line with this, transiently
      transfected RAW264.7 cells with alpha-synuclein showed arachidonic acid release
      and punctate alpha-synuclein staining upon phospholipase A2 activation. The
      ability of arachidonic acid to drive alpha-synuclein to aggregate was independent
      of its oxidation state. CONCLUSION: We present data that suggest a biological
      context for the previously reported clinical observation that linked mutations in
      PLA2G6, the gene responsible for the production of phospholipase A2, and early
      onset types of parkinsonism. Release of arachidonic acid, independent of its
      oxidation state, through activation of phospholipase A2-driven hydrolysis of
      phospholipid membranes, leads to the structural transition and aggregation of
      alpha-synuclein.

PMID- 29577852
TI  - In-Vitro Drug Dissolution Studies in Medicinal Compounds.
AB  - After oral administration, drug absorption from solid dosage forms depends on the
      release of the drug active compounds from the dosage form, the dissolution or
      solubilization of the drug under physiological conditions, and the permeability
      across the gastrointestinal tract. Dissolution testing is an essential part of
      designing more effective solid dosage forms in pharmaceutical industry. Moreover,
      dissolution testing contributes to the selection of appropriate formulation
      excipients for improving the dosage form efficiency. This study aims to analyze
      in-vitro drug dissolution testing in solid dosage forms since 2010 in order to
      present a comprehensive outlook of recent trends. In doing that the previous
      studies in the literature are summarized in the form of a table to demonstrate
      the apparatuses used for dissolution testing, the media in which the solid dosage
      form is dissolved, the method preferred for analysis from dissolution media, the
      conditions of analyses and the results obtained.

PMID- 29577853
TI  - New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for
      Therapeutic Intervention.
AB  - Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the
      regulation of electrolyte homeostasis and blood pressure. Although this role is
      undoubtedly important, it is not a hormonal action that attracts the most
      attention. Aldosterone seems to be very important as a local messenger in the
      pathology of cardiovascular diseases (CVD). In the last few years, the attention
      was focused on the correlation between raised aldosterone level and increased
      risk of cardiovascular events. It has been demonstrated that aldosterone
      contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic
      disorders, and oxidative stress leading to CVD development and progression. It
      used to be thought that the effects of aldosterone are mediated via classic
      nuclear receptors - mineralocorticoid receptors (MRs). Now we know that the
      mechanism of aldosterone action in the cardiovascular system (CVS) is much more
      complex since experimental and clinical studies indicate that MR blockade may be
      not sufficient to abolish aldosterone-induced harmful effects in CVS. Thus, the
      involvement of some other than MR, receptors, and factors is suggested. Moreover,
      in addition to the generally known genomic action of aldosterone, which involves
      MR activation, the nongenomic pathways are postulated in the mode of hormone
      action. More and more attention is focused on the membrane-coupled receptors,
      which mediate the rapid effects of aldosterone and have been already confirmed in
      different cells and tissues of CVS. Therefore, this brief review summarizes
      recent findings about new sides of aldosterone action in CVS that could be
      potential targets for therapeutic intervention.

PMID- 29577854
TI  - Flavonoids and its Neuroprotective Effects on Brain Ischemia and
      Neurodegenerative Diseases.
AB  - Brain ischemia is among the leading cause of death with majority of the cases are
      associated with ischemic strokes. It can occur in two forms of either focal or
      global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson
      diseases is also on the rise worldwide. These disorders have common similarities;
      i.e. they all affecting the central nervous system with debilitating effect to
      the patient. In this review, we look into the promising role of flavonoids, a
      natural bioactive compound found abundant in vegetables, fruits and traditional
      herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin
      and baicalin have shown promising neuroprotective effects against ischemic
      induced injury. Besides anticancer, antioxidant and immunomodulation properties,
      flavonoid also exerts neuroprotective effects by increases neuronal viability,
      increases tissue perfusion and cerebral blood flow and reduce ischemic-related
      apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and
      reduces loss of dopaminergic neurons in the brain. These results suggesting
      flavonoids might be able to serve as a potential therapeutic agent in brain
      disorders.

PMID- 29577855
TI  - Nanoparticles in Cancer Treatment: Opportunities and Obstacles.
AB  - In the United States, the estimated number of new cancer cases in 2018 will be
      approx. 1.7 million. Historically, combination chemotherapy has been the primary
      choice of treatment. However, chemotherapeutics have pharmaceutical limitations,
      among which include problems with stability and aqueous solubility. Likewise,
      dose limiting toxicity is significant with nonspecific toxicity to healthy cells,
      hair loss, loss of appetite, peripheral neuropathy and diarrhea being typical
      side effects. The emergence of Multidrug resistance (MDR) also presents s a
      significant challenge for the successful treatment of cancer whereby cancer cells
      become cross resistant to many of the chemotherapeutic agents used.
      Nanotechnology presents a new frontier for cancer treatment. It holds potential
      in minimizing systemic toxicity through the development of functionalized
      particles for targeted treatment. They also provide an alternative strategy to
      circumvent multidrug resistance as they have a capacity to by-pass the drug
      efflux mechanism associated with this phenotype. Aside from the advantages they
      offer in treatment, nanoparticles are also emerging to be valuable diagnostic
      entities. This article highlights the various ways nanotechnology is being used
      to improve the treatment and management of cancer. We also discuss the
      opportunities and obstacles in this area and provide an up to date review of
      progress in the treatment of cancer.

PMID- 29577856
TI  - Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a
      nos2b Signaling.
AB  - BACKGROUND: Vascular network formation induced by angiogenesis plays an important
      role in many physiological and pathological processes. However, the role of blood
      flow and underlying mechanisms in vascular network formation, for example for the
      development of the caudal vein plexus (CVP), is poorly understood. OBJECTIVE: The
      aim of this study was to explore the role of ERK5-klf2a-nos2b signaling in the
      CVP angiogenesis. METHOD AND RESULTS: In this study on tnnt2a-MO injection and
      chemical blood flow modulator treatment in zebrafish embryos, we demonstrated
      that decreased blood flow disrupted CVP formation. The hemodynamic force was
      quantitatively analyzed. Furthermore, CVP angiogenesis in zebrafish embryos was
      inhibited by disruption of the blood flow downstream effectors ERK5, klf2a, and
      nos2b in response to treatment with the ERK5 specific inhibitor and to injection
      of klf2a-MO, nos2b-MO. Overexpression of klf2a mRNA or nos2b mRNA restored
      vascular defects in tnnt2a or klf2a morphants. The data suggest that flow-induced
      ERK5-klf2a-nos2b signaling is involved in CVP angiogenesis in zebrafish embryos.
      CONCLUSION: We have demonstrated that blood flow is essential for vascular
      network formation, specifically for CVP angiogenesis in zebrafish. A novel
      genetic and mechanical mechanism was discovered in which ERK5 facilitates the
      integration of blood flow with the downstream klf2a-nos2b signaling for CVP
      angiogenesis.

PMID- 29577857
TI  - Erythropoietin Protects Retina Against Ceramide 2-Induced Damage in Rat.
AB  - BACKGROUND: Ceramide plays critical roles in cell proliferation, senescence and
      apoptosis, and is implicated in neurodegenerative diseases, etc. To clarify if
      ceramide plays some roles in retinal diseases, we established in vivo and in
      vitro retinal injury models with ceramide 2 (C2) treatment. In addition,
      Erythropoietin (EPO), which showed protective effects on retinal cells and blood
      retinal barrier (BRB), was also tested for its protection and possible
      mechanism(s) in these models. METHODS: Male Sprague-Dawley rats were divided into
      four groups, i.e., normal control, vehicle control, C2 treatment, and C2+EPO
      treatment. After intravitreal injection, the rats were examined for eye fundus,
      electroretinogram, histological study, and immunostaining, etc. In vitro, retinal
      neuronal cell line (R28) and the primary human retinal microvascular endothelial
      cells (HRMECs) were treated with C2, cell viability assay, transendothelial
      electrical resistance (TEER) and BRB-related molecules were studied to test the
      protective effect of EPO. RESULTS: Intravitreal C2-treatment caused significant
      vision loss in rats, as reflected by reduced b-wave amplitude, increased TUNEL
      positive cells and GFAP immunostaining in retina. Another major retinal injury
      observed was BRB breakdown following C2- treatment. Such C2-induced injuries were
      further confirmed by in vitro study. When HRMECs were treated with C2, the TEER
      was significantly reduced. The mechanisms for C2 to induce such injuries might be
      through evidently increased expressions of the related molecules like plasmalemma
      vesicle-associated protein (PLVAP or PV-1), ecto- 5'-nucleotidase (CD73) and
      intercellular adhesion molecule-1 (ICAM-1), as observed in C2-treated R28 cells.
      All these injuries induced by C2 were significantly prevented by EPO both in vivo
      and in vitro, and its protective mechanisms here might be, in addition to
      neuroprotective, closely related to its maintenance of BRB integrity, through
      reducing the expressions of PV-1, CD73 and ICAM-1. CONCLUSION: C2 could induce
      severe retinal injury, and such injuries could be effectively prevented by EPO
      treatment.

PMID- 29577858
TI  - Expression and Prognostic Relevance of GAGE1 and XAGE1 Cancer/Testis Antigens in
      Head and Neck Squamous Cell Carcinoma.
AB  - BACKGROUND: In the last decades, survival rates in head and neck squamous cell
      carcinoma (HNSCC) have not changed, with a five-year survival of only 50%. Thus,
      there is a great need for the identification of new molecular targets and
      development of novel therapeutic strategies. Cancer-testis antigens (CTAs) are
      expressed in various types of tumor but rarely in healthy normal tissues.
      Therefore, they appear as ideal targets for immunotherapy approaches, as well as,
      unique markers for cancer diagnosis/prognosis. OBJECTIVE: This study evaluated
      the expression pattern of cancer/testis antigens (CTA) in HNSCC samples and
      correlated the expression data with the clinicopathological prognostic variables.
      METHODS: An in silico screening was performed using all CTA genes cataloged on
      the CTDatabase and the expression of the eight CTA genes (ARMC3, DDX53, FTHL17,
      GAGE1, MAGEA11, SYCE1, TCP11, and XAGE1) was examined in 89 HNSCC and 20 normal
      mucosa samples using RT-PCR analysis. RESULTS: GAGE1 (48.3%), XAGE1 (40.4%) and
      MAGEA11 (19.1%) were frequently and specifically expressed in HNSCC samples and
      68.5% of the cases expressed at least one of these antigens. Moreover, GAGE1 and
      XAGE1 mRNA positivity was significantly associated with the presence of
      metastasis in the lymph nodes (p=0.038 and p=0.023, respectively) and, by
      multivariate analysis, male gender (p=0.032), advanced clinical stage (p=0.018)
      and mRNA positivity for GAGE1 (p=0.010) were independent prognostic factors for
      overall survival. CONCLUSION: These findings suggest GAGE1 and XAGE1 expressions
      to be useful as prognostic markers for HNSCC.

PMID- 29577859
TI  - Update on Asthma Genetics: Results From Meta-Analyses of Candidate Gene
      Association Studies.
AB  - Several studies have investigated the risk factors associated with asthma. Both
      genetic and environmental factors are considered to contribute to asthma
      susceptibility. Individual genetic association studies usually suffer from small
      sample size leading to biased results. Meta-analysis is a powerful tool that has
      the potential to resolve this limitation by increasing the statistical power of
      analyses. The current review summarizes the recent knowledge concerning genetic
      factors involved in asthma predisposition based on meta-analyses. Using the
      keywords: asthma, meta-analysis, polymorphism, we searched Pubmed, Medline,
      Embase and Google Scholar databases for the associated articles. Genetic
      polymorphisms in twenty-three genes are associated with asthma risk in meta
      analyses. However, polymorphisms in nine genes showed none significant
      association. These findings are used to assess the genetic risk factors and to
      understand the molecular pathways related to asthma.

PMID- 29577860
TI  - Prognostic Value of White Blood Cell Counts and C-reactive Protein in Acute
      Ischemic Stroke Patients After Intravenous Thrombolysis.
AB  - BACKGROUND: The prognostic value of White Blood Cell (WBC) counts and C-reactive
      Protein (CRP) in clinical outcomes of Acute Ischemic Stroke (AIS) patients after
      Intravenous Thrombolysis (IVT) remains unknown. We investigated the association
      of WBC counts and CRP with 3-month functional outcomes and all-cause mortality in
      AIS patients. METHODS: 447 AIS patients treated with IVT between May 2010 and May
      2017 were enrolled. WBC counts and CRP were measured within 24 hours after IVT.
      The main outcomes included poor functional outcomes (modified Rankin score >=3)
      at 3 months and 3-month all-cause mortality. RESULTS: High WBC counts were
      associated with poor functional outcomes (adjusted OR (odds ratio) 4.48; 95% CI
      (confidence interval) 2.00-10.03; P-trend<0.001) and with all-cause mortality
      (adjusted HR (hazard ratio) 2.19; 95% CI 1.07-4.49; P-trend=0.018). In addition,
      high CRP levels were associated with poor functional outcomes (adjusted OR 4.95;
      95% CI 1.39-17.65; Ptrend= 0.002). However, no significant association between
      high CRP levels and all-cause mortality was observed (adjusted HR 2.61; 95% CI
      0.80-8.47; P-trend=0.138). CONCLUSION: Our analysis indicated that elevated WBC
      counts and CRP levels after IVT can independently predict poor outcome among AIS
      patients.

PMID- 29577861
TI  - Kidney Dysfunction is Associated with a High Burden of Cerebral Small Vessel
      Disease in Primary Intracerebral Hemorrhage.
AB  - OBJECTIVES: To investigate the association of kidney function with the total
      burden of Cerebral Small Vessel Disease (CSVD) in primary Intracerebral
      Hemorrhage (pICH). METHODS: Cerebral magnetic resonance imagings of consecutively
      enrolled pICH patients were reviewed to assess for lacunes, White Matter
      Hyperintensity (WMH), Cerebral Microbleeds (CMBs) and Enlarged Perivascular
      Spaces (EPVS). Minor refinements to the CSVD score, namely modified CSVD score 1
      and 2, were made by incorporating different weightings of CSVD markers. Kidney
      function was assessed using the estimated Glomerular Filtration Rate (eGFR). We
      used ordinal regression analysis to assess the association of kidney function
      with the CSVD score and modified scores. RESULTS: In the 108 patients included,
      the presence of lacunes, CMBs, MWH and basal ganglia EPVS>10 was 27.8%, 67.6%,
      47.2% and 35.2%, respectively. In multivariable ordinal regression, a decreasing
      eGFR value was associated with an increased CSVD score [Odds Ratio (OR) 0.978,
      95% Confidence Interval (CI) 0.962 to 0.995, P=0.013], modified CSVD score 1 (OR
      0.973, 95% CI 0.957 to 0.990, P=0.002) and 2 (OR 0.969, 95% CI 0.953 to 0.986,
      P<0.001). The link between eGFR and the total burden of CSVD was significant in
      strictly deep pICH (P=0.011 for CSVD score; P=0.001 for modified score 1 and 2),
      but not strictly lobar pICH in subgroup analysis. CONCLUSIONS: Low eGFR is
      associated with a high burden of CSVD in patients with deep pICH, but not lobar
      pICH. Future studies are warranted to assess whether low eGFR is a potential
      therapeutic target for preventing the progress of CSVD burden for deep pICH.

PMID- 29577862
TI  - Increased Arterial Stiffness is Associated with Poor Collaterals in Acute
      Ischemic Stroke from Large Vessel Occlusion.
AB  - BACKGROUND: Cerebral collateral circulation is a network of arterial anastomotic
      channels capable of providing supplementary perfusion to brain regions in
      response to ischemic insults. Arterial stiffness could negatively affect
      collateral circulation development, by means of its effects on the structural
      intracerebral vasculature. OBJECTIVE: The aim of our study is to investigate a
      possible link between arterial stiffness and presence of collateral circulation
      in patients with acute ischemic stroke. METHODS: 113 patients (age: 74+/-12
      years) with acute anterior ischemic stroke underwent neuroimaging examination and
      24-hour blood pressure monitoring. Arterial Stiffness Index (ASI) and Pulse
      Pressure (PP) were assumed as surrogate measures of arterial stiffness.
      Collateral circulation was evaluated by means of the collateral grading system
      that was scored on a scale of 0-3. RESULTS: According to TOAST classification,
      etiology of ischemic stroke was the following: Large-Artery Atherosclerosis
      (LAA)(n:41), Cardioembolism (CE)(n:60), Undetermined Etiology (UE)(n:12).
      Logistic regression analysis showed that good predictors of poor collaterals were
      ASI (OR 2.78 for 0.1, 95% CI:1.19-6.50, p=0.01) and PP (OR 1.81 for 10 mmHg, 95%
      CI:1.01-3.22, p=0.04) in stroke from LAA. CONCLUSION: Our results suggest that,
      in patients with ischemic stroke from LAA, arterial stiffness may contribute to
      the impairment of collateral circulation and, therefore, it could reduce the
      beneficial effects of acute treatments.

PMID- 29577863
TI  - Hepatic Elimination of Drugs in Gestational Diabetes.
AB  - BACKGROUND: The liver is the major metabolic clearance organ for chemical agents
      from the human body. Pregnancy is associated with several physiological changes
      that may affect one or more of these factors, and also induces changes in the
      hepatic clearance of certain drugs. The aim of this paper was to review some of
      the currently available information in the field to provide some insights about
      the relevance of these changes on the clearance of some drugs. METHODS: A
      comprehensive literature search was carried out to identify eligible studies from
      MEDLINE/PubMed, EMBASE and SCIELO databases through 1970 first semester. RESULTS:
      Gestational Diabetes Mellitus (GDM) is a frequent disease commonly associated
      with other entities as obesity, hypertension, dyslipidemia, non-alcoholic fatty
      liver disease, prothrombotic conditions, changes in intestinal microbiome. These
      entities, together with the glycemic fluctuations associated with GDM might
      affect the determinants of the hepatic clearance (hepatic blood flow, the unbound
      fraction of drugs, and the hepatic intrinsic clearance). GDM is frequently
      associated with multi-drug treatments. While many of these drugs are cleared by
      the liver, little is known about the clinical relevance of these GDM associated
      pharmacokinetic changes. CONCLUSION: Considering the frequency of the disease and
      the effects that these pharmacokinetic changes might have on the mother and
      child, the need for further research seems advisable. In the meantime, cautious
      clinical judgment in the management of drug administration in women affected by
      this disease is recommended.

PMID- 29577864
TI  - Dyspnea in Cancer Patients: A Well-Known and Neglected Symptom.
AB  - BACKGROUND: Dyspnea is a very common and well-known symptom in patients with
      advanced cancer, but it is often neglected by physicians. Moreover, despite the
      high frequency of dyspnea, few controlled studies have been conducted on cancer
      patients. In most cases, this 'awareness of breathing with difficulty' and its
      severity can only be judged by the patient. Moderate or severe dyspnea is
      described in 20-80% of patients with advanced cancer and breathlessness is
      considered a prognostic factor for shorter survival, either alone or associated
      with other parameters. METHODS: I reviewed the literature and guidelines on the
      topic with the aims to focus on what is known and on future pathways to follow
      for the diagnosis and treatment of dyspnea. RESULTS: There is no uniformity
      regarding the definition of dyspnea; consequently, there is still no general
      agreement about which tools are the best to use in clinical practice to detect
      the presence and severity of this symptom. In addition to the difficulty of
      assessing the symptom, a further limit concerns the management of dyspnea: a very
      limited number of therapies, both pharmacological and otherwise, are currently
      available that lead to satisfactory outcomes. Opioids such as morphine remain the
      cornerstone of treating dyspnea. CONCLUSION: Dyspnea is a complex,
      multidimensional symptom that results from an interaction between factors and
      their causes, perception and expression. The main target of assessment and
      management is the intensity of dyspnea, as expressed by the patient, rather than
      the objective parameters of the disease. Although dyspnea is a very common
      symptom, debilitating and often difficult to control, especially in the terminal
      phase of the disease, few controlled studies have been conducted on cancer
      patients. Dyspnea remains a well-known but neglected symptom in advanced and
      terminal cancer patients. Future studies should be conducted regarding the
      careful assessment and management of this symptom.

PMID- 29577865
TI  - Synthesis and Biological Evaluation of New 1,3,4-Oxadiazoles as Potential
      Anticancer Agents and Enzyme Inhibitors.
AB  - BACKGROUND: 1,3,4-Oxadiazoles have been known with a wide variety of
      pharmacological activities including anticancer activity. OBJECTIVE: In this
      study, novel 2,5-disubstituted 1,3,4-oxadiazole derivatives were synthesized and
      evaluated for determining their anticancer, anticholinesterase and lipoxygenase
      (LOX) inhibitory activity. METHODS: All compounds were tested against C6 rat
      glioma, A549 human lung carcinoma and NIH/3T3 mouse embryo fibroblast cell lines
      to define cytotoxic concentrations and apoptosis induction levels which they
      cause. RESULTS: Many of the compounds exhibited remarkable potency that compounds
      2a, 2b, 2e, 2h and 2j against C6 cells and compounds 2a, 2b, 2d, 2g, 2i, 2j
      against A549 cells were found more active than cisplatin. Compound 2d namely, 2
      [(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-chlorophenyl)ethan-1-one
      induced apoptosis of A549 cells with 74.9% whereas cisplatin caused 70.9%
      percentage. CONCLUSION: Among them, compounds 2d and 2j against A549 cell line,
      compounds 2b and 2e against both tumor cell lines showed selective cytotoxicity
      evaluating the inhibition concentration against NIH/3T3 cell line. None of the
      compounds showed significant acetylcholinesterase (AChE) and lipoxygenase
      inhibitory activities.

PMID- 29577867
TI  - Platelet Activation Polymorphisms in Ischemia.
AB  - BACKGROUND: Ischemia is a multifactorial disorder in which several genetic and
      environmental factors are involved. Platelets are the major causative agents of
      this disease because their elevated activity and aggregation would increase the
      risk of atherosclerosis and thrombosis, as well as ischemia. A number of
      polymorphisms in platelet receptors can increase the risk of ischemia and single
      nucleotide polymorphisms (SNPs) have been detected in platelets. In addition,
      polymorphisms in other genes have been shown to cause platelet adhesion and
      aggregation that plays a role in ischemia. Patients respond differently to anti
      platelet drugs which are used to treat patients with ischemia. Polymorphisms
      affect patients' responses to anti-platelet drugs, for instance, by increasing
      platelet activity and causing resistance of platelets to these drugs. Diagnosis
      of these polymorphisms can greatly contribute to better prediction of prognosis
      and response to treatment of patients, leading to more effective therapeutic
      strategies and a proper approach to ischemia. CONCLUSION: In this review, we have
      evaluated the role of polymorphisms involved in platelet activation and
      development of ischemia.

PMID- 29577866
TI  - Synthesis and Anticancer Properties of Novel Truncated Carbocyclic Nucleoside
      Analogues.
AB  - Series of novel truncated carbocyclic nucleoside analogues have been synthesized
      from the versatile starting material D-ribose and their anticancer activities
      have been evaluated. The nucleoside analogues induced cytotoxicity in breast and
      ovarian cancer cell lines. These compounds are less cytotoxic to normal kidney
      cell line (HEK 293) as compared to the cancer cells. Among the synthesized
      compounds, 1b and 1d showed the better cytotoxic effect with IC50 44 and 54 MUM,
      in MCF7 cells, respectively. These compounds inactivate the important signaling
      kinases AKT and mTOR and thereby induce autophagy. Collectively our observation
      suggests that compound 1b and 1d inhibit the cancer cell proliferation through
      induction of autophagy mode of cell death.

PMID- 29577868
TI  - Regulation of Smooth Muscle Myosin Light Chain Phosphatase by Multisite
      Phosphorylation of the Myosin Targeting Subunit, MYPT1.
AB  - BACKGROUND: Smooth muscle contraction is triggered primarily by activation of
      Ca2+/calmodulin-dependent myosin light chain kinase leading to phosphorylation of
      the regulatory light chains of myosin II. Numerous contractile stimuli also
      induce inhibition of myosin light chain phosphatase thereby prolonging the
      contractile response. The phosphatase is a trimeric enzyme containing a catalytic
      subunit, a regulatory, myosin-binding subunit (MYPT1) and a third subunit of
      uncertain function. MYPT1 is phosphorylated at multiple sites by several kinases,
      which regulate phosphatase activity, protein-protein interactions and subcellular
      localization. The best-characterized phosphorylation events involve
      phosphorylation by Rho-associated coiled-coil kinase (ROCK) at T697 and T855,
      which inhibits phosphatase activity, and phosphorylation by cAMP- or
      cGMPdependent protein kinases (PKA and PKG, respectively) at S696, T697, S854 and
      T855, which has no effect on phosphatase activity. Furthermore, phosphorylation
      by ROCK at T697 and T855 prevents phosphorylation by PKA or PKG at the
      neighboring serine residues. Some 30 phosphorylation sites have been identified
      in MYPT1 with many more suggested by large-scale phosphoproteomic studies. It is
      important to gain as complete understanding as possible of the complex
      phosphorylation-mediated mechanisms of regulation of MYPT1 functions in part
      because of their involvement in pathological processes. For example,
      dysfunctional MYPT1 phosphorylation has been implicated in the pathogenesis of
      several vascular disorders, including type 2 diabetes. CONCLUSION: Much effort is
      now being devoted to the development of novel therapeutics targeting MYPT1 and
      specific kinases involved in the phosphorylation of MYPT1.

PMID- 29577869
TI  - Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide
      (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues.
AB  - BACKGROUND: Membrane transport protein organic anion transporting polypeptide
      (OATP) 1B3 mediates the cellular uptake of many clinically important drugs
      including anti-cancer drugs (e.g., paclitaxel). In addition to the well
      recognized hepatic expression and function of OATP1B3 [herein named liver-type
      (Lt) OATP1B3], OATP1B3 also expresses in cancers and has been postulated to play
      a role in cancer therapy, presumably by facilitating the influx of anti-cancer
      drugs. Recently, a cancer type (Ct)-OATP1B3 mRNA variant was identified in colon
      and lung cancer tissues, which encodes truncated Ct-OATP1B3 with negligible
      transport activity. Other than in colon and lung cancers, reports on mRNA
      expression of OATP1B3 in other cancers cannot distinguish between the Ltand Ct
      OATP1B3. OBJECTIVE: The current studies were designed to characterize the
      expression of Lt- and Ct-OATP1B3 mRNA in ovarian, prostate, bladder, breast, and
      lung tissues. METHODS: Lt- and Ct-OATP1B3 isoform-specific PCR primers were
      utilized to determine the mRNA levels of Lt- and Ct-OATP1B3, respectively. An
      expression vector expressing green fluorescent protein (GFP)-tagged Lt-OATP1B3
      was transiently transfected into the ovarian cancer cell line SKOV3. Confocal
      live-cell microscopy was utilized to determine the localization of GFP-Lt-OATP1B3
      in SKOV3 cells. RESULTS: For the first time, Lt-OATP1B3 mRNA was detected in
      ovarian, prostate, bladder and breast cancers. The localization of GFP-Lt-OATP1B3
      on the plasma membrane of SKOV3 cells after transient transfection was readily
      detected by confocal microscopy. CONCLUSION: Our findings are supportive of the
      potential role of Lt-OATP1B3 in cancer cells.

PMID- 29577870
TI  - Conflicts of Interest in Clinical Guidelines: Lack of Authors and Disclosures in
      the AAOMS White Papers.
AB  - PURPOSE: The purpose of this study was to evaluate current state of authorship,
      financial disclosures, and conflicts of interest in position papers published by
      the American Association of Oral and Maxillofacial Surgeons (AAOMS). MATERIALS
      AND METHODS: This is a cross-sectional review of the position papers published by
      the AAOMS from 2013 to 2017. Primary outcome variables include position papers
      published by the AAOMS. Secondary outcome variables include declaration of
      authorship, financial disclosures, and financial payments. The Open Payments
      Database for financial disclosures was reviewed for the year the position paper
      was published and the immediate preceding year. RESULTS: Ten position papers were
      published by the AAOMS from 2013 to 2017. Of the 10 papers, authorship was listed
      in 3, and none explicitly addressed the presence or absence of financial
      disclosures or conflicts of interest. Contributors to 3 of the 3 authored papers
      were found at review of the Open Payments Database to have received industry
      funding in the year the position paper was published and the immediate preceding
      year. The remuneration ranged from less than $1,000 to $554,006.02. CONCLUSION:
      Position papers published by the AAOMS lack standardization for authorship and
      statements on potential financial disclosure. The authors suggest full
      disclosures of authorship and authors' conflicts of interest should be stated on
      all position papers to provide transparency to the process.

PMID- 29577871
TI  - Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the
      insulin responses in male mice.
AB  - The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long
      noncoding RNA and its overexpression is associated with the development of many
      types of malignancy. MALAT1 null mice show no overt phenotype. However, in
      transcriptome analysis of MALAT1 null mice we found significant upregulation of
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulated antioxidant
      genes including Nqo1 and Cat with significant reduction in reactive oxygen
      species (ROS) and greatly reduced ROS-generated protein carbonylation in
      hepatocyte and islets. We performed lncRNA pulldown assay using biotinylated
      antisense oligonucleotides against MALAT1 and found MALAT1 interacted with Nrf2,
      suggesting Nrf2 is transcriptionally regulated by MALAT1. Exposure to excessive
      ROS has been shown to cause insulin resistance through activation of c-Jun N
      terminal kinase (JNK) which leads to inhibition of insulin receptor substrate 1
      (IRS-1) and insulin-induced phosphorylation of serine/threonine kinase Akt. We
      found MALAT1 ablation suppressed JNK activity with concomitant insulin-induced
      activation of IRS-1 and phosphorylation of Akt suggesting MALAT1 regulated
      insulin responses. MALAT1 null mice exhibited sensitized insulin-signaling
      response to fast-refeeding and glucose/insulin challenges and significantly
      increased insulin secretion in response to glucose challenge in isolated MALAT1
      null islets, suggesting an increased insulin sensitivity. In summary, we
      demonstrate that MALAT1 plays an important role in regulating insulin sensitivity
      and has the potential as a therapeutic target for the treatment of diabetes as
      well as other diseases caused by excessive exposure to ROS.

PMID- 29577873
TI  - Intermittent hypoxia-generated ROS contributes to intracellular zinc regulation
      that limits ischemia/reperfusion injury in adult rat cardiomyocyte.
AB  - Intermittent hypoxia (IH) has been shown to exert cardioprotective effects
      against ischemia/reperfusion (I/R) injury through the preservation of ion
      homeostasis. I/R dramatically elevated cytosolic Zn2+ and caused cardiomyocyte
      death. However, the role of IH exposure in the relationship between Zn2+
      regulation and cardioprotection is still unclear. The aim of the present study
      was to study whether IH exposure could help in intracellular Zn2+ regulation,
      hence contributing to cardioprotection against I/R injury. Adult rat
      cardiomyocytes were exposed to IH (5% O2, 5% CO2 and balanced N2) for 30 min
      followed by 30 min of normoxia (21% O2, 5% CO2 and balanced N2). Changes in
      intracellular Zn2+ concentration were determined using a Zn2+-specific
      fluorescent dye, FluoZin-3 or RhodZin-3. Fluorescence was monitored under an
      inverted fluorescent or confocal microscope. The results demonstrated that I/R or
      2,2'-dithiodipyridine (DTDP), a reactive disulphide compound, induced Zn2+
      release from metallothioneins (MTs), subsequently causing cytosolic Zn2+
      overload, which in turn increased intracellular Zn2+ entry into the mitochondria
      via a Ca2+ uniporter, hence inducing mitochondrial membrane potential loss, and
      eventually led to cell death. However, the cytosolic Zn2+ overload and cell death
      caused by I/R or DTDP was significantly reduced by treatment of cardiomyocytes
      with IH. The findings from this study suggest that IH might exert its
      cardioprotective effect through reducing the I/R-induced cytosolic Zn2+ overload
      and cell death in cardiomyocytes.

PMID- 29577872
TI  - Adaptive reduction of human myometrium contractile activity in response to
      prolonged uterine stretch during term and twin pregnancy. Role of TREK-1 channel.
AB  - Quiescence of myometrium contractile activity allows uterine expansion to
      accommodate the growing fetus and prevents preterm labor particularly during
      excessive uterine stretch in multiple pregnancy. However, the mechanisms
      regulating uterine response to stretch are unclear. We tested the hypothesis that
      prolonged uterine stretch is associated with decreased myometrium contractile
      activity via activation of TWIK-related K+ channel (TREK-1). Pregnant women at
      different gestational age (preterm and term) and uterine stretch (singleton and
      twin pregnancy) were studied, and uterine strips were isolated for measurement of
      contractile activity and TREK-1 channel expression/activity. Both oxytocin- and
      KCl-induced contraction were reduced in term vs preterm pregnancy and in twin vs
      singleton pregnancy. Oxytocin contraction was reduced in uterine segments exposed
      to 8 g stretch compared to control tissues under 2 g basal tension. TREK-1 mRNA
      expression and protein levels were augmented in Singleton-Term vs Singleton
      Preterm, and in uterine strips exposed to 8 g stretch. The TREK-1 activator
      arachidonic acid reduced oxytocin contraction in preterm and term, singleton and
      twin pregnant uterus. The TREK-1 blocker l-methionine enhanced oxytocin
      contraction in Singleton-Term and twin pregnant uterus, and reversed the
      decreases in contraction in uterine strips exposed to prolonged stretch.
      Carboprost-induced uterine contraction was also reduced by arachidonic acid and
      enhanced by l-methionine. Thus, myometrium contraction decreases with gestational
      age and uterine expansion in twin pregnancy. The results suggest that prolonged
      stretch enhances the expression/activity of TREK-1 channel, leading to decreased
      myometrium contractile activity and maintained healthy term pregnancy
      particularly in multiple pregnancy.

PMID- 29577874
TI  - The subesophageal ganglion modulates locust inter-leg sensory-motor interactions
      via contralateral pathways.
AB  - The neural control of insect locomotion is distributed among various body
      segments. Local pattern-generating circuits at the thoracic ganglia interact with
      incoming sensory signals and central descending commands from the head ganglia.
      The evidence from different insect preparations suggests that the subesophageal
      ganglion (SEG) may play an important role in locomotion-related tasks. In a
      previous study, we demonstrated that the locust SEG modulates the coupling
      pattern between segmental leg CPGs in the absence of sensory feedback. Here, we
      investigated its role in processing and transmitting sensory information to the
      leg motor centers and mapped the major related neural pathways. Specifically, the
      intra- and inter-segmental transfer of leg-feedback were studied by
      simultaneously monitoring motor responses and descending signals from the SEG.
      Our findings reveal a crucial role of the SEG in the transfer of intersegmental,
      but not intrasegmental, signals. Additional lesion experiments, in which the
      intersegmental connectives were cut at different locations, together with double
      nerve staining, indicated that sensory signals are mainly transferred to the SEG
      via the connective contralateral to the stimulated leg. We therefore suggest
      that, similar to data reported for vertebrates, insect leg sensory-motor loops
      comprise contralateral ascending pathways to the head and ipsilateral descending
      ones.

PMID- 29577875
TI  - Characterization of antibody-C1q interactions by Biolayer Interferometry.
AB  - IgG molecules exert important effector functions including complement-dependent
      cytotoxicity (CDC). Different IgG isotypes induce CDC effect with variation,
      largely due to their differential binding to C1q, the initiating molecule of the
      classical CDC pathway. Here we report a method to characterize the binding of IgG
      to C1q using label-free technique. With this method, we determined the binding
      affinities of multiple IgG1, IgG2 and IgG4 antibodies to C1q. To explore whether
      antigen binding to antibodies affects C1q binding, we assessed the binding of
      Trastuzumab and Adalimumab with bound antigen proteins to C1q. The results showed
      that although the two tested IgG1 mAbs alone bind C1q similarly, their FC binding
      to C1q was significantly impacted by antigen binding to the Fab. The data
      suggested that the first step of complement pathway, whether C1q binds target
      cell bound antibody molecules, may significantly affect the CDC activities of
      antibody drugs.

PMID- 29577876
TI  - Data Transparency.

PMID- 29577877
TI  - Monomorphic pathogens: The case of Candidatus Xenohaliotis californiensis from
      abalone in California, USA and Baja California, Mexico.
AB  - Withering syndrome (WS) is a chronic wasting disease affecting abalone species
      attributed to the pathogen Candidatus Xenohaliotis californiensis (CXc). Wild
      populations of blue (Haliotis fulgens) and yellow (H. corrugata) abalone have
      experienced unusual mortality rates since 2009 off the peninsula of Baja
      California and WS has been hypothesized as a possible cause. Currently, little
      information is available about the genetic diversity of CXc and particularly the
      possible existence of strains differing in pathogenicity. In a recent
      phylogenetic analysis, we characterized five coding genes from this rickettsial
      pathogen. Here, we analyze those genes and two additional intergenic non-coding
      regions following multi-locus sequence typing (MLST) and multi-spacer typing
      (MST) approaches to assess the genetic variability of CXc and its relationship
      with blue, yellow and red (H. rufescens) abalone. Moreover, we used 16S rRNA
      pyrosequencing reads from gut microbiomes of blue and yellow abalone to complete
      the genetic characterization of this prokaryote. The presence of CXc was
      investigated in more than 150 abalone of the three species; furthermore, a total
      of 385 DNA sequences and 7117 16S rRNA reads from Candidatus Xenohaliotis
      californiensis were used to evaluate its population genetic structure. Our
      findings suggest the absence of polymorphism in the DNA sequences of analyzed
      loci and the presence of a single lineage of CXc infecting abalone from
      California (USA) and Baja California (Mexico). We posit that the absence of
      genetic variably in this marine rickettsia may be the result of evolutionary and
      ecological processes.

PMID- 29577878
TI  - Establishment of a tumor neovascularization animal model with biomaterials in
      rabbit corneal pouch.
AB  - AIMS: The present animal model of tumor neovascularization most often used by
      researchers is zebrafish. For studies on human breast cancer cell
      neovascularization, a new animal model was established to enable a more
      convenient study of tumor neovascularization. MAIN METHODS: A sodium alginate
      gelatin blend gel system was used to design the new animal model. The model was
      established using rabbit corneal pouch implantation. Then, the animal model was
      validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. KEY
      FINDINGS: The experiment intuitively observed the relationship between tumor and
      neovascularization, and demonstrated the advantages of this animal model in the
      study of tumor neovascularization. SIGNIFICANCE: The use of sodium alginate
      gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is
      a novel and ideal method for the study of neovascularization. It may be a better
      animal model for expanding the research in this area.

PMID- 29577879
TI  - Overexpressed miR-145 inhibits osteoclastogenesis in RANKL-induced bone marrow
      derived macrophages and ovariectomized mice by regulation of Smad3.
AB  - BACKGROUND: MicroRNAs (miRs) play an important role in osteoclastogenesis.
      However, no study has investigated the underlying molecular mechanisms of miR-145
      in this process. The purpose of the present study was to investigate the role of
      miR-145 and its post-transcriptional mechanism in the progression of osteoclast
      differentiation. METHODS: Macrophage colony stimulating factor (M-CSF) and
      receptor activator of nuclear factor-kB ligand (RANKL) were used to induce
      osteoclastogenesis originated from bone marrow-derived macrophages (BMMs). Female
      C57BL/6J mice were divided into sham, OVX, OVX + NC-agomir and OVX + miR-145
      agomir groups. Tartrate-resistant acid phosphatase (TRAP) staining was performed
      to identify osteoclasts in-vitro and in-vivo. The mRNA and protein levels in
      osteoclast and tibia were assayed by qRT-PCR and western blotting, respectively.
      RESULTS: miR-145 expression was inhibited in RANKL-induced osteoclastogenesis,
      whereas overexpression of miR-145 attenuated it. We further found that Smad3 is a
      direct target gene of miR-145 by binding with its 3'-UTR. Overexpression of miR
      145 significantly suppressed Smad3 mRNA and protein expression. In-vivo, miR-145
      agomir treatment inhibited osteoclast activity in OVX mice by inhibiting Smad3
      expression. CONCLUSION: We provide the evidence that over-expression of miR-145
      could inhibit osteoclast differentiation, at least partially, by decreasing Smad3
      expression.

PMID- 29577880
TI  - Nanoparticles designed to regulate tumor microenvironment for cancer therapy.
AB  - Increasing understanding in tumor pathology reveals that tumor microenvironment
      (TME), which supports tumor progression and poses barriers for available
      therapies, takes a great responsibility in inefficient treatment and poor
      prognosis. In recent years, the versatile nanotechnology employed in TME
      regulation has made great progress. The nanoparticles (NPs) can be tailored as
      needed to accurately target TME components by distinguishing healthy tissues from
      malignancy, and to regulate TME to promote tumor regression. Meanwhile, the
      emerging microRNAs (miRNAs) demonstrate great potentials for TME regulation, but
      are regrettably restricted by quick degradation. NPs systems enable the
      successful delivery of miRNA to TME without the limitation, expanding the
      application of nucleic acid drug. In this review, we summarized recent NPs-based
      strategies aiming at regulating TME in different ways, including anti
      angiogenesis, extracellular matrix (ECM) remodeling, tumor-associated fibroblasts
      (TAFs) treatment and tumor-associated macrophages (TAMs) treatment, along with
      the miRNAs-loaded NPs for TME regulation. Catching and utilizing the features of
      TME for NPs design can contribute to reversing drug-resistance, optimized drug
      distribution, and eventually more efficient cancer therapy.

PMID- 29577881
TI  - On Doctors and Their Operas: A Critical (and Lyrical) Analysis of Medicine in
      Opera.
AB  - The goal of this research was to analyze the opera repertoire in terms of
      contents of physician roles. An additional goal was to pinpoint significant
      characters and passages that exemplify the changing role and perception of
      medicine in society over five centuries. A systematic search was performed.
      Musical characteristics and performing roles, and their determinants, were
      tabulated and formally analyzed. Of 493 operas listed, 53 (10.7%) were identified
      as having either a patient and/or doctor as characters. These operas span 239
      years, from 1777 to 2016. Beyond unspecified Family Medicine and Generalists,
      some operas could be attributed to medical specialties, including 3 (5.7%) to
      Respiratory. Most interestingly, the 34 operas (6.9%) with physician roles are
      all represented by male characters, distributed by voice register mostly in the
      grave chords. Overall, the composer that appears with the highest interest in
      reporting disease is Giuseppe Verdi, with nine operas that include medical
      doctors. Finally, a trend can be observed regarding the evolving role of doctors,
      from mostly minor, buffal roles, either with magical or comical components in the
      18th century, to a professional/technical physician more recently. Opera depicts
      a changing perception of the roles of doctors throughout history, with a blatant
      gender bias that still persists.

PMID- 29577882
TI  - TPC2-mediated Ca2+ signaling is required for the establishment of synchronized
      activity in developing zebrafish primary motor neurons.
AB  - During the development of the early spinal circuitry in zebrafish, spontaneous
      Ca2+ transients in the primary motor neurons (PMNs) are reported to transform
      from being slow and uncorrelated, to being rapid, synchronized and patterned. In
      this study, we demonstrated that in intact zebrafish, Ca2+ release via two-pore
      channel type 2 (TPC2) from acidic stores/endolysosomes is required for the
      establishment of synchronized activity in the PMNs. Using the
      SAIGFF213A;UAS:GCaMP7a double-transgenic zebrafish line, Ca2+ transients were
      visualized in the caudal PMNs (CaPs). TPC2 inhibition via molecular, genetic or
      pharmacological means attenuated the CaP Ca2+ transients, and decreased the
      normal ipsilateral correlation and contralateral anti-correlation, indicating a
      disruption in normal spinal circuitry maturation. Furthermore, treatment with MS
      222 resulted in a complete (but reversible) inhibition of the CaP Ca2+
      transients, as well as a significant decrease in the concentration of the Ca2+
      mobilizing messenger, nicotinic acid adenine diphosphate (NAADP) in whole embryo
      extract. Together, our new data suggest a novel function for NAADP/TPC2-mediated
      Ca2+ signaling in the development, coordination, and maturation of the spinal
      network in zebrafish embryos.

PMID- 29577883
TI  - The cellular prion protein promotes olfactory sensory neuron survival and axon
      targeting during adult neurogenesis.
AB  - The cellular prion protein (PrPC) has been associated with diverse biological
      processes including cell signaling, neurogenesis, and neuroprotection, but its
      physiological function(s) remain ambiguous. Here we determine the role of PrPC in
      adult neurogenesis using the olfactory system model in transgenic mice. Olfactory
      sensory neurons (OSNs) within the olfactory sensory epithelium (OSE) undergo
      neurogenesis, integration, and turnover even into adulthood. The neurogenic
      processes of proliferation, differentiation/maturation, and axon targeting were
      evaluated in wild type, PrP-overexpressing, and PrP-null transgenic mice. Our
      results indicate that PrPC plays a role in maintaining mature OSNs within the
      epithelium: overexpression of PrPC resulted in greater survival of mitotically
      active cells within the OSE, whereas absence of prion protein resulted in fewer
      cells being maintained over time. These results are supported by both
      quantitative PCR analysis of gene expression and protein analysis characteristic
      of OSN differentiation. Finally, evaluation of axon migration determined that OSN
      axon targeting in the olfactory bulb is PrPC dose-dependent. Together, these
      findings provide new mechanistic insight into the neuroprotective role for PrPC
      in adult OSE neurogenesis, whereby more mature neurons are stably maintained in
      animals expressing PrPC.

PMID- 29577884
TI  - Regional-specific effects of cerebral ischemia/reperfusion and
      dehydroepiandrosterone on synaptic NMDAR/PSD-95 complex in male Wistar rats.
AB  - Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over
      activation represent well-known hallmarks of cerebral ischemia/reperfusion (I/R)
      injury, still, expression of proteins involved in this aspect of I/R
      pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone
      (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R
      induced changes up to date remains questionable. Therefore, I/R-governed
      alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit
      composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology
      alone or following DHEA treatment were examined. For that purpose, adult male
      Wistar rats were treated with a single dose of vehicle or DHEA (20 mg/kg i.p.) 4
      h following sham operation or 15 min bilateral common carotid artery occlusion.
      Western blot was used for analyses of synaptic protein expressions in hippocampus
      and prefrontal cortex, while neuronal morphology was assessed using Nissl
      staining. Regional-specific postischemic changes were detected on protein level
      i.e. signs of neuronal damage in CA1 area was accompanied with hippocampal
      vGluT1, NR1, NR2B enhancement and PSD-95 decrement, while histological changes
      observed in layer III were associated with decreased NR1 subunit in prefrontal
      cortex. Under physiological conditions DHEA had no effect on protein and
      histological appearance, while in ischemic milieu it restored hippocampal PSD-95
      and NR1 in prefrontal cortex to the control level. Along with intact neurons,
      ones characterized by morphology observed in I/R group were also present. Future
      studies involving NMDAR-related intracellular signaling and immunohistochemical
      analysis will reveal precise effects of I/R and DHEA treatment in selected brain
      regions.

PMID- 29577885
TI  - Primary microglia isolation from mixed cell cultures of neonatal mouse brain
      tissue.
AB  - BACKGROUND: Microglia are the main resident immunological cells of the central
      nervous system (CNS) that are functionally equivalent to macrophages. However,
      due to the cellular heterogeneity of the brain, it is technically challenging to
      obtain highly specific, healthy microglia with the desired phenotype in
      sufficient yield for in vivo experiments. NEW METHOD: This study presents a new
      and easy method for the isolation of microglia cells from mouse pups (P1-P3).
      This method consists of a 20-day protocol, divided in three sections: mixed cell
      culture, culture maintaining (astrocytes growing), and isolation after astrocytes
      confluence. RESULTS: This procedure produces microglia with no astrocyte, neuron
      and oligodendrocyte precursors cells contamination that are functionally active
      to answer inflammatory responses based on the measurement of cell and
      inflammatory markers. This technique requires approximately three hours for the
      isolation of neonatal mixed cell culture, 20 to 22 days for microglia growing and
      two days before starting experiments from pure and healthy microglia. COMPARISON
      WITH EXISTING METHODS AND CONCLUSIONS: This study presents an isolation protocol
      that is adapted from existing methods and is economic, rapid, not tedious, with
      little manipulation time and work. This method also allows to isolate large
      amount of high specific microglia cells with no specific phenotype and with great
      reproducibility and efficiently. This study provides a detailed description of
      the methods that is routinely used in our laboratory for the isolation and the
      culture of microglia, with emphasis on the steps that are deemed most critical
      for obtaining large amount of pure and healthy cultures.

PMID- 29577886
TI  - Mouse models of ALS: Past, present and future.
AB  - Genome sequencing of both sporadic and familial patients of Amyotrophic Lateral
      Sclerosis (ALS) has led to the identification of new genes that are both
      contributing and causative in the disease. This gene discovery has come at an
      unprecedented rate, and much of it in recent years. Knowledge of these genetic
      mutations provides us with opportunities to uncover new and related mechanisms,
      increasing our understanding of the disease and bringing us closer to defined
      therapies for patients. Mouse models have played an important role in our current
      understanding of the pathophysiology of ALS and have served as important
      preclinical models in testing new therapeutics. With these new gene discoveries,
      new mouse models will follow. The information derived from these new models will
      depend on the careful construction and importantly, an understanding of the
      capabilities and limitations of each of the models. The genetic discovery in ALS
      comes at a time when genetic engineering technologies in mice are highly
      efficient through CRISPR/Cas9 and can be applied to a wide array of genetic
      backgrounds. New mouse resources in the forms of the Collaborative Cross and
      Diversity Outbred panels provide us with unique opportunities to study these
      mutations on diverse genetic backgrounds, and importantly in the context of a
      population. This review focuses on the mouse models of the past and present, and
      discusses exciting new opportunities for mouse models of the future.

PMID- 29577887
TI  - Disinhibiting neurons in the dorsomedial hypothalamus delays the onset of
      exertional fatigue and exhaustion in rats exercising in a warm environment.
AB  - Stimulants cause hyperthermia, in part, by increasing heat generation through
      exercise. Stimulants also delay the onset of fatigue and exhaustion allowing
      animals to exercise longer. If used in a warm environment, this combination
      (increased exercise and decreased fatigue) can cause heat stroke. The dorsomedial
      hypothalamus (DMH) is involved in mediating locomotion from stimulants.
      Furthermore, inhibiting the DMH decreases locomotion and prevents hyperthermia in
      rats given stimulants in a warm environment. Whether the DMH is involved in
      mediating exercise-induced fatigue and exhaustion is not known. We hypothesized
      that disinhibiting neurons in the dorsomedial hypothalamus (DMH) would delay the
      onset of fatigue and exhaustion in animals exercising in a warm environment. To
      test this hypothesis, we used automated video tracking software to measure
      fatigue and exhaustion. In rats, using wearable mini-pumps, we demonstrated that
      disinhibiting the DMH, via bicuculline perfusion (5 uM), increased the duration
      of exercise in a warm environment as compared to control animals (25 +/- 3 min vs
      15 +/- 2 min). Bicuculline-perfused animals also had higher temperatures at
      exhaustion (41.4 +/- 0.2  degrees C vs 40.0 +/- 0.4  degrees C). Disinhibiting
      neurons in the DMH also increased the time to fatigue. Our data show that the
      same region of the hypothalamus that is involved in mediating locomotion to
      stimulants, is also involved in controlling exhaustion and fatigue. These
      findings have implications for understanding the cause and treatment of stimulant
      induced-hyperthermia.

PMID- 29577888
TI  - Inhibition of basal and amphetamine-stimulated extracellular signal-regulated
      kinase (ERK) phosphorylation in the rat forebrain by muscarinic acetylcholine M4
      receptors.
AB  - The mitogen-activated protein kinase (MAPK), especially its extracellular signal
      regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian
      brain. While ERK is central to cell signaling and neural activities, the
      regulation of ERK by transmitters is poorly understood. In this study, the role
      of acetylcholine in the regulation of ERK was investigated in adult rat striatum
      in vivo. We focused on muscarinic M1 and M4 receptors, two principal muscarinic
      acetylcholine (mACh) receptor subtypes in the striatum. A systemic injection of
      the M1-preferring antagonist telenzepine did not alter ERK phosphorylation in the
      two subdivisions of the striatum, the caudate putamen and nucleus accumbens.
      Similarly, telenzepine did not affect ERK phosphorylation in the medial
      prefrontal cortex (mPFC), hippocampus, and cerebellum. Moreover, telenzepine had
      no effect on the ERK phosphorylation induced by dopamine stimulation with the
      psychostimulant amphetamine. In contrast to telenzepine, the M4-preferring
      antagonist tropicamide consistently increased ERK phosphorylation in the striatum
      and mPFC. This increase was rapid and transient. Tropicamide and amphetamine when
      coadministered at subthreshold doses induced a significant increase in ERK
      phosphorylation. These results demonstrate that mACh receptors exert a subtype
      specific modulation of ERK in striatal and mPFC neurons. While the M1 receptor
      antagonist has no effect on ERK phosphorylation, M4 receptors inhibit
      constitutive and dopamine-stimulated ERK phosphorylation in these dopamine
      innervated brain regions.

PMID- 29577889
TI  - Amyloid beta peptides, locus coeruleus-norepinephrine system and dense core
      vesicles.
AB  - The evolution of peptidergic signaling systems in the central nervous system
      serves a distinct and crucial role in brain processes and function. The diversity
      of physiological peptides and the complexity of their regulation and secretion
      from the dense core vesicles (DCV) throughout the brain is a topic greatly in
      need of investigation, though recent years have shed light on cellular and
      molecular mechanisms that are summarized in this review. Here, we focus on the
      convergence of peptidergic systems onto the Locus Coeruleus (LC), the sole
      provider of norepinephrine (NE) to the cortex and hippocampus, via large DCV. As
      the LC-NE system is one of the first regions of the brain to undergo degeneration
      in Alzheimer's Disease (AD), and markers of DCV have consistently been
      demonstrated to have biomarker potential for AD progression, here we summarize
      the current literature linking the LC-NE system with DCV dysregulation and Abeta
      peptides. We also include neuroanatomical data suggesting that the building
      blocks of senile plaques, Abeta monomers, may be localized to DCV of the LC and
      noradrenergic axon terminals of the prefrontal cortex. Finally, we explore the
      putative consequences of chronic stress on Abeta production and the role that DCV
      may play in LC degeneration. Clinical data of immunological markers of DCV in AD
      patients are discussed.

PMID- 29577890
TI  - Host and parasite morphology influence congruence between host and parasite
      phylogenies.
AB  - Comparisons of host and parasite phylogenies often show varying degrees of
      phylogenetic congruence. However, few studies have rigorously explored the
      factors driving this variation. Multiple factors such as host or parasite
      morphology may govern the degree of phylogenetic congruence. An ideal analysis
      for understanding the factors correlated with congruence would focus on a diverse
      host-parasite system for increased variation and statistical power. In this
      study, we focused on the Brueelia-complex, a diverse and widespread group of
      feather lice that primarily parasitise songbirds. We generated a molecular
      phylogeny of the lice and compared this tree with a phylogeny of their avian
      hosts. We also tested for the contribution of each host-parasite association to
      the overall congruence. The two trees overall were significantly congruent, but
      the contribution of individual associations to this congruence varied. To
      understand this variation, we developed a novel approach to test whether host,
      parasite or biogeographic factors were statistically associated with patterns of
      congruence. Both host plumage dimorphism and parasite ecomorphology were
      associated with patterns of congruence, whereas host body size, other plumage
      traits and biogeography were not. Our results lay the framework for future
      studies to further elucidate how these factors influence the process of host
      parasite coevolution.

PMID- 29577891
TI  - Assessment of two CRISPR-Cas9 genome editing protocols for rapid generation of
      Trypanosoma cruzi gene knockout mutants.
AB  - CRISPR/Cas9 technology has been used to edit genomes in a variety of organisms.
      Using the GP72 gene as a target sequence, we tested two distinct approaches to
      generate Trypanosoma cruzi knockout mutants using the Cas9 nuclease and in vitro
      transcribed single guide RNA. Highly efficient rates of disruption of GP72 were
      achieved either by transfecting parasites stably expressing Streptococcus
      pyogenes Cas9 with single guide RNA or by transfecting wild type parasites with
      recombinant Staphylococcus aureus Cas9 previously associated with single guide
      RNA. In both protocols, we used single-stranded oligonucleotides as a repair
      template for homologous recombination and insertion of stop codons in the target
      gene.

PMID- 29577892
TI  - A partition of Toxoplasma gondii genotypes across spatial gradients and among
      host species, and decreased parasite diversity towards areas of human settlement
      in North America.
AB  - Toxoplasma gondii counts among the most consequential food-borne parasites, and
      although the parasite occurs in a wide range of wild and domesticated animals,
      farms may constitute a specific and important locus of transmission. If so,
      parasites in animals that inhabit agricultural habitats might be suspected of
      harbouring genetically distinct parasite types. To better understand habitat
      effects pertinent to this parasite's transmission, we compiled and analysed
      existing genotypic data of 623 samples from animals across a proximity gradient
      from areas of human settlement to the wilderness in North America. To facilitate
      such analysis, T. gondii isolates were divided into three groups: (i) from farm
      bound animals (with the most limited home ranges on farms); (ii) from free
      roaming animals (with wider home ranges on or near farms); and (iii) from
      wildlife. In addition, parasite genotype distribution in different animal species
      was analysed. We observed no absolute limitation of any of five major genotypes
      to any one habitat; however, the frequency of four genotypes decreased across the
      gradient from the farm-bound group, to the free-roaming group, then the wildlife,
      whereas a fifth genotype increased along that gradient. Genetic diversity was
      greater in free-roaming than in farm-bound animals. The genotypic composition of
      parasites in wildlife differed from those in farm-bound and free-roaming animals.
      Furthermore, parasite genotypes differed among host species. We conclude that T.
      gondii genotype distributions are influenced by the spatial habitat and host
      species composition, and parasite diversity decreases towards areas of human
      settlement, elucidating facts which may influence transmission dynamics and
      zoonotic potential in this ubiquitous but regionally variable parasite.

PMID- 29577894
TI  - Bilateral quinolinic acid-induced lipid peroxidation, decreased striatal
      monoamine levels and neurobehavioral deficits are ameliorated by GIP receptor
      agonist D-Ala2GIP in rat model of Huntington's disease.
AB  - Huntington's disease (HD) is an inherited complex progressive neurodegenerative
      disorder with an established etiopathology linked to neuronal oxidative stress
      and corticostriatal excitotoxicity. Present study explores the effects of glucose
      dependent insulinotropic polypeptide (GIP) receptor agonist on the
      neurobehavioral sequelae of quinolinic acid-induced phenotype of Huntington's
      disease in rats. Bilateral administration of quinolinic acid (300 nmol/4 MUl) to
      the rat striatum led to characteristic deficits in, locomotor activity, motor
      coordination, neuromuscular coordination and short-term episodic memory.
      Therapeutic treatment for 14 days with a stable and brain penetrating GIP
      receptor agonist, D-Ala2GIP (100 nmol/kg, i.p.), attenuated the neurobehavioral
      deficits due to quinolinic acid (QA) administration. Protective actions of D
      Ala2GIP were sensitive to blockade with a GIP receptor antagonist, (Pro3)GIP (50
      nmol/kg, i.p.), indicating specific involvement of GIP receptor signaling
      pathway. Stimulation of GIP receptor with D-Ala2GIP attenuated lipid
      peroxidation, evidenced by reduced levels of brain malondialdehyde (MDA), and
      restoration of reduced glutathione (GSH) levels in brain. Quinolinic acid
      administration led to significant loss of striatal monoamines, e.g.,
      norepinephrine, epinephrine, serotonin, dopamine, and metabolites, 3,4
      Dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5
      Hydroxyindoleacetic acid (5-HIAA). D-Ala2GIP attenuated the QA-induced depletion
      of striatal monoamines, without affecting the monoamine degradation pathways.
      Thus, observed effects with D-Ala2GIP in the QA-induced Huntington's disease
      model could be attributable to reduction in lipid peroxidation, restoration of
      endogenous antioxidants and decreased striatal monoamine levels. These findings
      together suggest that stimulation of GIP receptor signaling pathway in brain
      could be a potential therapeutic strategy in the symptomatic management of
      Huntington's disease.

PMID- 29577893
TI  - Participation of transient receptor potential vanilloid 1 in paclitaxel-induced
      acute visceral and peripheral nociception in rodents.
AB  - The clinical use of paclitaxel as a chemotherapeutic agent is limited by the
      severe acute and chronic hypersensitivity caused when it is administered via
      intraperitoneal or intravenous routes. Thus far, evidence has suggested that
      transient receptor potential vanilloid-1 (TRPV1) has a key role in the chronic
      neuropathy induced by paclitaxel. Despite this, the role of TRPV1 in paclitaxel 
      related acute nociception, especially the development of visceral nociception,
      has not been evaluated. Thus, the goal of this study was to evaluate the
      participation of TRPV1 in a model of acute nociception induced by paclitaxel in
      rats and mice. A single intraperitoneal (i.p.) paclitaxel administration (1
      mg/kg, i.p.) produced an immediate visceral nociception response 1 h after
      administration, caused mechanical and heat hypersensitivity, and diminished
      burrowing behaviour 24 h after administration. These nociceptive responses were
      reduced by SB-366791 treatment (0.5 mg/kg, i.p., a TRPV1 antagonist). In
      addition, TRPV1-positive sensory fibre ablation (using resiniferatoxin, 200
      ug/kg, s.c.) reduced visceral nociception and mechanical or heat hypersensitivity
      caused by paclitaxel injection. Similarly, TRPV1 deficient mice showed a
      pronounced reduction in mechanical allodynia to paclitaxel acute injection and
      did not develop heat hypersensitivity. Moreover, 24 h after its injection,
      paclitaxel induced chemical hypersensitivity to capsaicin (a TRPV1 agonist, 0.01
      nmol/site) and increased TRPV1 immunoreactivity in the dorsal root ganglion and
      sciatic nerve. In conclusion, TRPV1 is involved in mechanical and heat
      hypersensitivity and spontaneous-pain behaviour induced 24 h after a single
      paclitaxel injection. This receptor is also involved in visceral nociception
      induced immediately after paclitaxel administration.

PMID- 29577895
TI  - Biophysical characteristics of hematopoietic cells during division.
AB  - Cell division is managed by a complex and coordinated sequence of cytoskeleton
      alterations that give rise to major morphological changes. During dividing the
      cleavage furrow of the cell is significantly stiffened due to the accumulation of
      actomyosin. However, it is unclear whether the stiffness on top of the cell is
      changed or not. Here, we used atomic force microscopy to measure stiffness on
      this location of non-adhesion Jurkat T cell and its derivative D1.1 cell from
      interphase to cytokinesis. The results showed that during division the cell
      stiffness significantly increases at anaphase and telophase. These increases in
      cell stiffness are most likely due to the cell surface tension created by the
      pulling forces of the microtubules to separate sister chromatids in the anaphase
      and the contraction forces of the contractile ring to separate the mother cell
      into daughters in the telophase. The dynamic measurement of cell elasticity
      during cell division may be used as a tool to gain further insight into the
      involved molecules and mechanisms.

PMID- 29577896
TI  - Platelet endothelial aggregation receptor-1 (PEAR1) is involved in C2C12 myoblast
      differentiation.
AB  - C2C12 murine myoblasts are a common model for studying muscle differentiation.
      Platelet endothelial aggregation receptor-1 (PEAR1), an epidermal growth factor
      repeat-containing transmembrane receptor, is known to participate in platelet
      contact-induced activation. In the present study, we demonstrated that PEAR1 is
      involved in the differentiation of C2C12 murine myoblasts. Western blotting and
      immunofluorescence staining were used to determine PEAR1 expression and
      localization during C2C12 cell differentiation. Subsequently, PEAR1 expression
      was activated and inhibited using clustered regularly interspaced short
      palindromic repeats-dCas9 technology to explore its effects on this process.
      PEAR1 expression was found to increase over the course of C2C12 cell
      differentiation. This protein was predominately localized on the membrane of
      these cells, where it clustered upon induction of differentiation. Expression of
      the myogenic markers Desmin, MYOG, and MYH2 revealed that PEAR1 positively
      regulated C2C12 cell differentiation. Moreover, induction of muscle injury by
      administration of bupivacaine to mice indicated that PEAR1 might play a role in
      muscle regeneration. In summary, our study confirmed the involvement of PEAR1 in
      C2C12 cell differentiation, contributing to our understanding of the molecular
      mechanisms underlying muscle development.

PMID- 29577897
TI  - The RNA binding protein tristetraprolin down-regulates autophagy in lung
      adenocarcinoma cells.
AB  - Tristetraprolin (TTP) is the most well-known member of RNA-binding zinc-finger
      protein that play a significant role in accelerating mRNA decay. Increasingly
      studies have reported that TTP was functioned as a tumor suppressor gene in
      several types of carcinomas, while its underlying mechanism is not clear yet. In
      the current study, we found that TTP overexpression decreased cell proliferation
      and increased cell death in lung adenocarcinoma cells, with the cell cycle arrest
      at the S phase. Remarkably, instead of inducing cell apoptosis directly, TTP
      overexpression alters cell autophagy. Our studies demonstrate that TTP
      overexpression has no effect on apoptosis related genes, but decreases the
      expression of autophagy-related genes, including Beclin 1 and LC3II. The level of
      autophagy flux assessed by infection with the mGFP-RFP-LC3 adenovirus
      construction has been blocked by TTP overexpression. Moreover, the autophagic
      vacuoles number detected by transmission electron microscopy decreased with TTP
      expression up-regulation. Our results indicate, for the first time, that TTP
      suppresses cell proliferation and increases cell death through cell autophagy
      pathway in lung cancer cells. Our study provides a new angle of view for TTP
      function as a tumor suppressor which could be targeted in tumor treatment.

PMID- 29577898
TI  - Reproductive endocrinology of environmental nitrate.
AB  - Nitrate is a widespread contaminant of aquatic ecosystems and drinking water. It
      is also broadly active in organismal physiology, and as such, has the potential
      to both enhance and disrupt normal physiological function. In animals, nitrate is
      a proposed endocrine disrupter that is converted in vivo to nitrite and nitric
      oxide. Nitric oxide, in particular, is a potent cell signaling molecule that
      participates in diverse biological pathways and events. Here, we review in vivo
      nitrate cycling and downstream mechanistic physiology, with an emphasis on
      reproductive outcomes. However, in many cases, the research produces
      contradictory results, in part because there is good evidence that nitrate
      follows a non-monotonic dose-response curve. This conundrum highlights an array
      of opportunities for scientists from different fields to collaborate for a full
      understanding of nitrate physiology. Opposing conclusions are especially likely
      when in vivo/in vitro, long term/short term, high dose/low dose, or
      hypoxia/normoxia studies are compared. We conclude that in vivo studies are most
      appropriate for testing an organism's integrated endocrine response to nitrate.
      Based on the limited available studies, there is a generalized trend that shorter
      term studies (less than 1 month) or studies involving low doses (<=5 mg/L NO3-N)
      cause steroid hormone levels to decline. Studies that last more than a month
      and/or involve higher, but still environmentally relevant, exposures (>50-100
      mg/L NO3-N) cause steroid hormone levels to increase. Very high nitrate doses
      (>500 mg/L NO3-N) are cytotoxic in many species. Hypoxia and acidity are likely
      to intensify the effects of nitrate. For study design, degree of study animal
      reproductive maturity or activity is important, with immature/reproductively
      quiescent animals responding to nitrate differently, compared with reproductively
      active animals. A detailed table of studies is presented.

PMID- 29577899
TI  - Integrin expression and glycosylation patterns regulate cell-matrix adhesion and
      alter with breast cancer progression.
AB  - Integrins are the major cell adhesion glycoproteins involved in cell
      extracellular matrix (ECM) interaction and metastasis. Further, glycosylation on
      integrin is necessary for its proper folding and functionality. Herein,
      differential expression of integrins viz., alphavbeta3 and alphavbeta6 was
      examined in MDA-MB-231, MDA-MB-468 and MCF-10A cells, which signify three
      different stages of breast cancer development from highly metastatic to non
      tumorigenic stage. The expression of alphavbeta3 and alphavbeta6 integrins at
      mRNA and protein levels was observed in all three cell lines and the results
      displayed a distinct pattern of expression. Highly metastatic cells showed
      enhanced expression of alphavbeta3 than moderate metastatic and non-tumorigenic
      cells. The scenario was reversed in case of alphavbeta6 integrin, which was
      strongly expressed in moderate metastatic and non-tumorigenic cells. N
      glycosylation of alphavbeta3 and alphavbeta6 integrins is required for the
      attachment of cells to ECM proteins like fibronectin. The cell adhesion
      properties were found to be different in these cancer cells with respect to the
      type of integrins expressed. The results testify that alphavbeta3 integrin in
      highly metastatic cells, alphavbeta6 integrin in both moderate metastatic and non
      tumorigenic cells play an important role in cell adhesion. The investigation
      typify that N-glycosylation on integrins is also necessary for cell-ECM
      interaction. Further, glycosylation inhibition by Swainsonine is found to be more
      detrimental to invasive property of moderate metastatic cells. Conclusively,
      types of integrins expressed as well as their N-glycosylation pattern alter
      during the course of breast cancer progression.

PMID- 29577900
TI  - Protective effects of kenpaullone on cardiomyocytes following H2O2-induced
      oxidative stress are attributed to inhibition of connexin 43 degradation by
      SGSM3.
AB  - A previous study showed that small G protein signaling modulator 3 (SGSM3) was
      highly correlated with Cx43 in heart functions and that high levels of SGSM3 may
      induce Cx43 turnover through lysosomal degradation in infarcted rat hearts. Here,
      we investigated the protective effects of kenpaullone on cardiomyocytes following
      H2O2-induced oxidative stress mediated by the interaction of SGSM3 with Cx43. We
      found that the gap junction protein Cx43 was significantly down-regulated in an
      H2O2 concentration-dependent manner, whereas expression of SGSM3 was up-regulated
      upon H2O2 exposure in H9c2 cells. The effect of kenpaullone pretreatment on H2O2
      induced cytotoxicity was evaluated in H9c2 cells. H2O2 markedly increased the
      release of lactate dehydrogenase (LDH), while kenpaullone pretreatment suppressed
      LDH release in H9c2 cells. Moreover, kenpaullone pretreatment significantly
      reduced ROS fluorescence intensity and significantly down-regulated the level of
      apoptosis-activating genes (cleaved caspase-3, cleaved caspase-9 and cytochrome
      C), autophagy markers (LC3A/B), and the Cx43-interacting partner SGSM3. These
      results suggest that kenpaullone plays a role in protecting cardiomyocytes from
      oxidative stress and that the turnover of Cx43 through SGSM3-induced lysosomal
      degradation underlies the anti-apoptotic effect of kenpaullone.

PMID- 29577901
TI  - O-GlcNAc site-mapping of liver X receptor-alpha and O-GlcNAc transferase.
AB  - The Liver X Receptor alpha (LXRalpha) belongs to the nuclear receptor superfamily
      and plays an essential role in regulating cholesterol, lipid and glucose
      metabolism and inflammatory responses. We have previously shown that LXRalpha is
      post-translationally modified by O-linked beta-N-acetyl-glucosamine (O-GlcNAc)
      with increased transcriptional activity. Moreover, we showed that LXRalpha
      associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver.
      In this study, we report that human LXRalpha is O-GlcNAc modified in its N
      terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O
      GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42. However, O-GlcNAc site
      mutations did not modulate LXRalpha transactivation of selected target gene
      promoters in vitro. Peptide array and co-immunoprecipitation assays demonstrate
      that LXRalpha interacts with OGT in its NTD and ligand-binding domain (LBD) in a
      ligand-independent fashion. Moreover, we map two new O-GlcNAc sites in the
      longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain
      and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids
      826-832) in the intervening region (Int-D) within the catalytic domain. We also
      map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437
      in the TPRs 11-13 domain. Future studies will reveal the biological role of
      identified O-GlcNAc sites in LXRalpha and OGT.

PMID- 29577902
TI  - Identification of aberrant circular RNA expression and its potential clinical
      value in primary great saphenous vein varicosities.
AB  - This study aimed to identify aberrant circRNA expression in primary great
      saphenous vein varicosities (PGSVVs) and investigate its potential clinical
      significance. High-throughput sequencing was applied to analyze the differential
      expression of circRNAs in three paired vein samples of PGSVVs and a control
      group. Computational bioinformatics analyses, including gene ontology (GO)
      analysis and encyclopedia of genes and genomes (KEGG) pathway analysis, were
      performed to further enrich microRNA data. Real-time quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) was used to verify the selected
      aberrant circRNAs in all vein samples, and a receiver operating characteristic
      (ROC) curve was plotted to evaluate the diagnostic and potential clinical
      significance. A total of 232 circRNAs were significantly aberrantly expressed in
      PGSVVs, including 105 and 127 upregulated and downregulated circRNAs,
      respectively. The predicted top 10 downstream miRNAs of the significantly altered
      circRNAs are hsa-miR-103a-2-5p, hsa-miR-141-5p, hsa-miR-3692-5p, hsa-miR-4659a
      3p, hsa-miR-4659b-3p, hsa-miR-4691-5p, hsa-miR-4778-3p, hsa-miR-6738-3p, hsa-miR
      6792-3p and hsa-miR-6873-3p. GO analysis revealed that the most enriched and
      meaningful biological process, cellular component, and molecular function terms
      were related to the regulation of catabolic processes, the cytoplasm and ATP
      binding, respectively. The most enriched and meaningful pathways revealed by KEGG
      pathway analysis were related to "axon guidance" "vitamin digestion and
      absorption" and "NF-Kappa B signaling pathway". Hsa_circ_0006427 (P = 0.007),
      hsa_circ_0089810 (P = 0.044) and hsa_circ_0005267 (P = 0.049) were significantly
      downregulated in the PGSVV group relative to their expression levels in the
      control group, and the area under the ROC curve was 0.9091, 0.8025 and 0.8148,
      respectively. This study demonstrated that circRNAs were differentially expressed
      in PGSVVs, and highlights the crucial roles of circRNAs in the pathogenesis of
      PGSVVs and indicates that hsa_circ_0006427, hsa_circ_0089810 and hsa_circ_0005267
      might be potential diagnostic and clinical biological markers.

PMID- 29577903
TI  - Hypertonic saline regulates microglial M2 polarization via miR-200b/KLF4 in
      cerebral edema treatment.
AB  - BACKGROUND: Hypertonic saline (HS) has been used clinically for treatment of
      cerebral edema for decades. Previously we have demonstrated that HS alleviates
      cerebral edema via regulating water/ion channel protein and attenuating
      neuroinflammation. However, whether HS treatment triggers microglia polarization
      and its regulatory mechanism during this process is unclear. METHODS AND RESULTS:
      The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery
      occlusion (MCAO) were used for assessment of neuroinflammation and microglia
      functions. Treatment of 10% HS not only significantly reduced infarct size and
      ipsilateral ischemic hemispheric brain water content (BWC) via attenuating
      ischemia-induction of TNF-alpha, IL-1beta, microglia M1 markers (iNOS, CD86) and
      miR-200b, but also increased neurotrophic factors such as IL-10 and IL-4,
      microglia M2 markers (Arg1, CD206) and Kruppel-like factor 4 (KLF4). Similar
      changes were confirmed in primary microglial cells subjected to hypoxia
      with/without HS in vitro. Importantly, overexpression of miR-200b was able to
      induce microglia M1 polarization via directly targeting KLF4. Restoring KLF4
      expression abolished this effect. On the contrary, miR-200b inhibitor or KLF4
      overexpression led to microglia M2 polarization. Mechanistically, KLF4 directly
      binds to promoter region of Agr1, thus inducing its transcription. Similar to
      treatment of HS, experimental overexpression of KLF4 in vivo exerted significant
      beneficial effects on ischemia-induced cerebral edema. However, knockdown of KLF4
      abrogated the benefits of HS. CONCLUSIONS: Hypertonic saline regulates microglial
      M2 polarization via miR-200b/KLF4 during its treatment of cerebral edema. This
      study may provide new insights of HS-related therapy for cerebral edema.

PMID- 29577904
TI  - Giantin is required for coordinated production of aggrecan, link protein and type
      XI collagen during chondrogenesis.
AB  - Extracellular matrix (ECM) constitutes a proper micro-environment for cell
      proliferation, migration and differentiation, as well as playing pivotal roles in
      developmental processes including endochondral ossification. Cartilage ECM is
      mainly composed of fibrous proteins, including collagen, proteoglycan, and
      hyaluronan. Because almost all ECM components are transported by intracellular
      vesicular transport systems, molecules that mediate vesicle transport are also
      important for endochondral ossification. Giantin, encoded by the Golgb1 gene, is
      a tethering factor for coatomer 1 (COPI) vesicles and functions in the cis-medial
      Golgi compartments. An insertion mutation in the Golgb1 gene, resulting in a lack
      of giantin protein expression, has been detected in ocd/ocd rats that exhibit a
      pleiotropic phenotype including osteochondrodysplasia. To reveal the function of
      giantin in chondrogenesis, the present study assessed the effects of loss of
      giantin expression on cartilage ECM and Golgi morphology. Giantin was expressed
      in normal, but not in ocd/ocd, chondrocytes in the epiphyseal areas of embryonic
      femurs, whereas GM130 was expressed in both normal and ocd/ocd chondrocytes. The
      staining intensities of safranin O and azan (aniline blue) were reduced and
      enhanced, respectively, in epiphyseal cartilage of ocd/ocd femurs. Immunostaining
      showed that levels of type II collagen and fibronectin were comparable in normal
      and ocd/ocd cartilage. Levels of type XI collagen were higher, while levels of
      aggrecan, link protein and hyaluronan were lower, in ocd/ocd than in normal
      cartilage, although semi-quantitative RT-PCR showed similar levels of type XI
      collagen, aggrecan and link protein mRNAs in normal and ocd/ocd cartilage.
      Isolated chondrocytes of ocd/ocd and normal rats showed similar immunostaining
      patterns for cis-, medial-, and trans-Golgi marker proteins, whereas monolayers
      of ocd/ocd chondrocytes showed reduced levels of aggrecan and link protein and
      increased level of type XI collagen in spite of similar transcripts levels. These
      findings suggest that giantin plays a pivotal role in coordinated production of
      aggrecan, link protein and type XI collagen in chondrocytes, and that loss of
      giantin causes osteochondrodysplasia with disturbance of these ECM components.

PMID- 29577905
TI  - Conditional reprogrammed human limbal epithelial cells represent a novel in vitro
      cell model for drug responses.
AB  - In this study, we established human limbal epithelial cells (LECs) from normal
      limbal tissues by using Conditional Reprogramming (CR) technology (refer to CR
      LEC cells in this study). We have successfully established CR-LEC cell strains
      from three human donors (3 out of 3), and normal rabbits (2 out of 2) and pig (1
      out of 1) as well. CR-LEC cells sustained a continuous and stable proliferation
      status with a normal karyotype, normal response to DNA damage, well-defined
      structured spheres in matrigel 3D culture. Responses of CR-LEC cells to IFN
      alpha2b, Ganciclovir and 5-Fluorouracil were different, suggesting that these
      drugs had different toxicities to these cells as expected. More important, there
      was no significant difference of responses to drugs between early and late
      passages of CR-LEC cells (p>0.05), indicating CR-LEC cells can serve a stable
      normal human cell model for toxicity assessment. Toxicity tests with monolayer
      cultures of CR-LEC cells were measured by staining the F-actin and Dsg-1
      expression. Toxicity of three drugs at LD50 concentration resulted in a gradually
      increased destruction of monolayer, which is, in accordance with the irritation
      grade of three drugs on human cornea epithelium. Therefore, CR-LEC cells provide
      a novel and reliable in vitro physiological cell model for corneal toxicity
      assessment.

PMID- 29577906
TI  - Soy undecapeptide induces Drosophila hind leg grooming via dopamine receptor.
AB  - beta-Conglycinin alpha subunit (323-333) [betaCGalpha(323-333)] is an exogenous
      neuromodulating undecapeptide found from enzymatic digest of beta-conglycinin, a
      soy major storage protein by mice behavior tests. We investigated effect of
      betaCGalpha(323-333) on Drosophila behavior. Oral administration of
      betaCGalpha(323-333) in Drosophila increased hind leg grooming, which may act
      through specific sets of neurons. It was reported that dopamine receptor (DopR)
      meditates hind leg grooming, and we tested involvement of DopR in betaCGalpha(323
      333)-induced hind leg grooming by using DopR knockout flies. In the wild type but
      not in the DopR-knockout flies, betaCGalpha(323-333) increased hind leg grooming.
      These results suggest that betaCGalpha(323-333) induces hind leg grooming via
      activating the DopR. This is the first report showing that exogenously
      administered peptide changes fly behaviors.

PMID- 29577907
TI  - Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent
      skin dermal fibroblast.
AB  - Cellular senescence suppresses cancer by inducing irreversible cell growth
      arrest. Nevertheless, senescent cells is proposed as causal link with aging and
      aging-related pathologies. The physiological beneficial functions of senescent
      cells are still of paucity. Here we show that senescent human dermal fibroblast
      accelerates keratinocytes scratch wound healing and stimulates differentiation of
      fibroblast. Using oxidative stress (100 MUM H2O2 exposure for 1 h) induction, we
      successfully triggered fibroblast senescence and developed senescence associated
      secretory phenotype (SASP). The induction of SASP was regulated by
      p38MAPK/MSK2/NF-kappaB pathway. Interestingly, inhibition of p38MAPK activation
      only partially suppressed SASP. However, SASP was significantly inhibited by
      SB747651A, a specific MSK inhibitor. Additionally, we demonstrate that SASP
      stimulates migration of keratinocytes and myofibroblast transition of fibroblast,
      through fold-increased secretion of growth factors, platelet-derived growth
      factor AA (PDGF-AA) and AB (PDGF-AB), transforming growth factor beta 1 (TGF
      beta1) and beta 2 (TGF-beta2), vascular endothelial growth factor A (VEGF-A) and
      D (VEGF-D), vascular endothelial growth factor receptor 2 (VEGFR2) and 3
      (VEGFR3). Importantly, we also confirmed ginsenoside Rb1 promoted SASP-mediated
      healing process via p38MAPK/MSK2/NF-kappaB pathway. The results pointed to
      senescent fibroblast as a potential mechanism of wound healing control in human
      skin. Further, it provided a candidate targeted for wound therapy.

PMID- 29577908
TI  - Promoter-associated proteins of EPAS1 identified by enChIP-MS - A putative role
      of HDX as a negative regulator.
AB  - Presence of perivascular neuroblastoma cells with high expression of hypoxia
      inducible factor (HIF)-2alpha correlates with distant metastasis and aggressive
      disease. Regulation of HIFs are traditionally considered to occur post
      translationally, but we have recently shown that HIF-2alpha is unconventionally
      regulated also at the transcriptional level in neuroblastoma cells. Regulatory
      factors binding directly to EPAS1 (encoding HIF-2alpha) to promote transcription
      are yet to be defined. Here, we employ the novel CRISPR/Cas9-based engineered DNA
      binding molecule-mediated chromatin immunoprecipitation (enChIP) - mass
      spectrometry (MS) methodology to, in an unbiased fashion, identify proteins that
      associate with the EPAS1 promoter under normoxic and hypoxic conditions. Our
      enChIP analysis resulted in 27 proteins binding to the EPAS1 promoter in
      neuroblastoma cells. In agreement with a general hypoxia-driven downregulation of
      gene transcription, the majority (24 out of 27) of proteins dissociate from the
      promoter at hypoxia. Among them were several nucleosome-associated proteins
      suggesting a general opening of chromatin as one explanation to induced EPAS1
      transcription at hypoxia. Of particular interest from the list of released
      factors at hypoxia was the highly divergent homeobox (HDX) transcription factor,
      that we show inversely correlates with HIF-2alpha in neuroblastoma cells. We
      propose a putative model where HDX negatively regulates EPAS1 expression through
      a release-of-inhibition mechanism.

PMID- 29577909
TI  - Genome-wide identification and expression analysis of the fatty acid desaturase
      genes in Medicago truncatula.
AB  - Fatty acid desaturases (FADs) are of great importance and play critical roles in
      regulating plant fatty acid (FA) compositions. But to date, no reports about
      characterization of the FAD genes have been reported in the model dicotyledonous
      grass species Medicago truncatula. In this study, using database searches, 20
      full-length FAD genes were identified in M. truncatula. These FAD genes were
      unevenly distributed on six chromosomes except the chromosome 6 and 8.
      Phylogenetic analysis showed the FAD genes in M. truncatula were clustered into
      six subfamilies and had similar exon number and intron phase in the same
      subfamily. Moreover, expression analysis based on qRT-PCR indicated these FAD
      genes were extensively involved in cold and heat responses. This study would
      provide an important foundation for future cloning and functional studies of FAD
      genes in M. truncatula and other related legume species.

PMID- 29577910
TI  - Blood Is Thicker: Hyperviscosity Syndrome.

PMID- 29577911
TI  - Long non coding RNA XIST as a prognostic cancer marker - A meta-analysis.
AB  - BACKGROUND: The X inactivate-specific transcript (XIST), derived from XIST gene,
      is aberrantly expressed in various cancers. High-expression of XIST is related to
      poor clinical outcome. This meta-analysis evaluated the potential role of XIST as
      novel predictor of prognosis in human cancer. MATERIALS AND METHODS: This meta
      analysis collected eligible studies about XIST and tumor prognosis through
      retrieving keywords in Web of Science, PubMed, Embase and the CNKI database, from
      1993 to August 21, 2017. The quantitative meta-analysis was carried out with
      Stata SE12.0 and RevMan3.23 software. The aim was to determine whether XIST
      expression is associated with cancer prognosis and clinicopathology. RESULTS: A
      total of 858 patients from 10 eligible studies were included in the final meta
      analysis. Overall, a significant negative association between XIST and overall
      survival (OS) time (HR = 2.62, 95% CI: 2.18-3.14) was observed. Statistical
      significance was also showed in subgroup meta-analysis stratified by the country,
      sample size, follow-up and publication year. It was reported that increased XIST
      was positively related to advanced clinical TNM stage (OR = 4.03, 95% CI: 2.22
      7.30), lymph node metastasis (LNM) (OR = 2.70, 95% CI: 1.73-4.21), distant
      metastasis (DM) (OR = 2.61, 95% CI: 1.57-4.33) and tumor size (OR = 3.10, 95% CI:
      2.24-4.30). CONCLUSIONS: LncRNA XIST may serve as a potential biomarker to
      predict solid tumor prognosis. This molecule can be effectively used to predict
      the clinical and pathological features of cancers.

PMID- 29577912
TI  - Comment on "Copeptin in heart failure: Review and meta-analysis" by Zhong Y et
      al.

PMID- 29577913
TI  - Reference limits of the urinary gamma-glutamyltransferase in a healthy population
      and effects of short-term storage on the enzyme activity.
AB  - BACKGROUND: Gamma-glutamyltransferase (GGT) is present mainly in proximal renal
      tubule, and urinary GGT is an indicator of tubular damage since it may show renal
      changes before they are identified by using conventional measurements. Therefore,
      it is of interest to establish the reference limits of urinary GGT for a healthy
      population, as well as to investigate the stability of GGT in urine samples
      stored at 4  degrees C and -20  degrees C. METHODS: GGT was assessed in urine
      samples from 127 healthy patients by use of a reference method based on the 5
      Amino-2-Nitrobenzoate formation. Stability of GGT was evaluated in 10 urine
      samples stored at temperatures of 4  degrees C and -20  degrees C for a period up
      to 4 weeks. RESULTS: Urinary GGT values for healthy volunteers were 14 U/g
      creatinine for the lower reference limit and 79 U/g creatinine for the upper
      reference limit. Urinary GGT values were approximately 56% lower in samples
      stored at -20  degrees C than fresh samples, while samples stored at 4  degrees C
      presented a decrease of 11% in GGT values compared to fresh samples. CONCLUSIONS:
      Reference limits for urinary GGT in healthy subjects were 14 to 79 U/g
      creatinine, and it is recommended to measure urinary GGT in fresh specimens.

PMID- 29577914
TI  - The importance of the learning process in ST analysis interpretation and its
      impact in improving clinical and neonatal outcomes.
AB  - BACKGROUND: Intrapartum fetal heart rate monitoring was introduced with the goal
      to reduce fetal hypoxia and deaths. However, continuous fetal heart rate
      monitoring has been shown to have a high sensitivity but also a high false
      positive rate. To improve specificity, adjunctive technologies have been
      developed to identify fetuses at risk for intrapartum asphyxia. Intensive
      research on the value of ST-segment analysis of the fetal electrocardiogram as an
      adjunct to standard electronic fetal monitoring in lowering the rates of fetal
      metabolic acidosis and operative deliveries has been ongoing. The conflicting
      results in randomized and observational studies may partly be due to differences
      in study design. OBJECTIVE: This study aims to determine the significance of the
      learning process for the introduction of ST analysis into clinical practice and
      its impact on initial and subsequent obstetric outcomes. STUDY DESIGN: This was a
      prospective observational study with the primary objective to evaluate the
      importance of the learning period on the rates of metabolic acidosis and
      operative deliveries after the implementation of ST analysis. The study was
      conducted at the Turku University Hospital, Turku, Finland, with 3400-4200 annual
      deliveries. The whole study population consisted of all 42,146 deliveries during
      the study period 2001 through 2011. The ST analysis usage rate was 18%. The data
      were collected prospectively from labors monitored with ST analysis as an adjunct
      to conventional intrapartum fetal heart rate monitoring. Primary endpoints were
      the rates of metabolic acidosis (cord artery pH <7.05 and an extracellular fluid
      compartment base deficit >12.0 mmol/L), fetal scalp blood sampling, and operative
      deliveries. Comparisons of these outcomes were made between the initiation period
      (the first 2 years) and the subsequent usage period (the next 9 years). RESULTS:
      In the whole study population the prevalence of cord pH <7.05 decreased from 1.5
      0.81% (relative risk, 0.54; 95% confidence interval, 0.43-0.67), the rate of
      cesarean deliveries from 17.2-14.1% (relative risk, 0.82; 95% confidence
      interval, 0.89-0.97), and the rate of fetal scalp blood sampling from 1.75-0.82%
      (relative risk, 0.47; 95% confidence interval, 0.38-0.58) when the 2 study
      periods were compared. In the ST analysis group, the frequency of cord metabolic
      acidosis rate was reduced from 1.0-0.25% (relative risk, 0.33; 95% confidence
      interval, 0.15-0.72). CONCLUSION: We provide evidence that the results improve
      over time and there is a learning curve in the introduction of the ST analysis
      method. This was demonstrated by the lower rates of metabolic acidosis and
      operative deliveries after the initial implementation period.

PMID- 29577915
TI  - Training contraceptive providers to offer intrauterine devices and implants in
      contraceptive care: a cluster randomized trial.
AB  - BACKGROUND: US unintended pregnancy rates remain high, and contraceptive
      providers are not universally trained to offer intrauterine devices and implants
      to women who wish to use these methods. OBJECTIVE: We sought to measure the
      impact of a provider training intervention on integration of intrauterine devices
      and implants into contraceptive care. STUDY DESIGN: We measured the impact of a
      continuing medical education-accredited provider training intervention on
      provider attitudes, knowledge, and practices in a cluster randomized trial in 40
      US health centers from 2011 through 2013. Twenty clinics were randomly assigned
      to the intervention arm; 20 offered routine care. Clinic staff participated in
      baseline and 1-year surveys assessing intrauterine device and implant knowledge,
      attitudes, and practices. We used a difference-in-differences approach to compare
      changes that occurred in the intervention sites to changes in the control sites 1
      year later. Prespecified outcome measures included: knowledge of patient
      eligibility for intrauterine devices and implants; attitudes about method safety;
      and counseling practices. We used multivariable regression with generalized
      estimating equations to account for clustering by clinic to examine intervention
      effects on provider outcomes 1 year later. RESULTS: Overall, we surveyed 576
      clinic staff (314 intervention, 262 control) at baseline and/or 1-year follow-up.
      The change in proportion of providers who believed that the intrauterine device
      was safe was greater in intervention (60% at baseline to 76% at follow-up) than
      control sites (66% at both times) (adjusted odds ratio, 2.48; 95% confidence
      interval, 1.13-5.4). Likewise, for the implant, the proportion increased from 57
      77% in intervention, compared to 61-65% in control sites (adjusted odds ratio,
      2.57; 95% confidence interval, 1.44-4.59). The proportion of providers who
      believed they were experienced to counsel on intrauterine devices also increased
      in intervention (53-67%) and remained the same in control sites (60%) (adjusted
      odds ratio, 1.89; 95% confidence interval, 1.04-3.44), and for the implant
      increased more in intervention (41-62%) compared to control sites (48-50%)
      (adjusted odds ratio, 2.30; 95% confidence interval, 1.28-4.12). Knowledge scores
      of patient eligibility for intrauterine devices increased at intervention sites
      (from 0.77-0.86) 6% more over time compared to control sites (from 0.78-0.80)
      (adjusted coefficient, 0.058; 95% confidence interval, 0.003-0.113). Knowledge
      scores of eligibility for intrauterine device and implant use with common medical
      conditions increased 15% more in intervention (0.65-0.79) compared to control
      sites (0.67-0.66) (adjusted coefficient, 0.15; 95% confidence interval, 0.09
      0.21). Routine discussion of intrauterine devices and implants by providers in
      intervention sites increased significantly, 71-87%, compared to in control sites,
      76-82% (adjusted odds ratio, 1.97; 95% confidence interval, 1.02-3.80).
      CONCLUSION: Professional guidelines encourage intrauterine device and implant
      competency for all contraceptive care providers. Integrating these methods into
      routine care is important for access. This replicable training intervention
      translating evidence into care had a sustained impact on provider attitudes,
      knowledge, and counseling practices, demonstrating significant changes in
      clinical care a full year after the training intervention.

PMID- 29577916
TI  - Prevention of obesity and diabetes in pregnancy: is it an impossible dream?
AB  - The obesity and diabetes epidemic is an unintended consequence of economic,
      social, and technological changes. In nonpregnancy, people identified as high
      risk to develop type 2 diabetes may delay progression by 30-70% with lifestyle
      interventions and pharmacological agents. In pregnancy, lifestyle interventions
      have been the primary focus to prevent fetal short- and long-term complications
      that may evolve into substantial weight gain and gestational diabetes mellitus.
      The dilemma for obstetricians is whether diabetes and obesity can be prevented
      and not simply treated after the fact. Interventions after women become pregnant
      may be too late to see the kinds of meaningful improvements in child and maternal
      health because there is a short interval from gestational diabetes mellitus
      diagnosis to delivery. Therefore, future efforts need to incorporate quality
      research, lifestyle interventions that designate time of initiation and duration
      during pregnancy, the preventative intervention of a prepregnant "fourth
      trimester," coupled with the concept of precision medicine so that there is the
      potential to make the impossible dream a reality.

PMID- 29577918
TI  - Blockade of Granzyme B Remarkably Improves Mucocutaneous Diseases with
      Keratinocyte Death in Interface Dermatitis.

PMID- 29577919
TI  - Evaluation of sPGA * BSA as an Outcome Measure and Treatment Target for Clinical
      Practice.
AB  - Clinical outcome measures are becoming more important in psoriasis treatment.
      Reliable and standardized measures of severity feasible for clinical practice are
      needed. Our objective was to investigate body surface area (BSA) and the product
      of BSA and static Physician Global Assessment (sPGA) (ie, BSA * sPGA) as
      potential proxy measures for PASI scores. Data were pooled from three
      multicenter, randomized, double-blind, placebo-controlled, phase 3 trials of
      ixekizumab in patients with moderate to severe psoriasis (UNCOVER-1, -2, -3; N =
      3,866). Assessments included the Psoriasis Area and Severity Index (PASI), BSA,
      and BSA * sPGA. Rank correlations between BSA * sPGA and PASI were stronger than
      between BSA and PASI (baseline, r = 0.759 vs. r = 0.707; week 12, r = 0.959 vs. r
      = 0.924). Week 12 concordance rates with PASI responses were as follows: for 75%
      reduction in PASI: BSA, 86.2%; BSA * sPGA, 93.8%; for 90% reduction in PASI: BSA,
      86.9%; BSA * sPGA, 88.2%. The 75% reduction in PASI positive and negative
      predictive values were higher for BSA * sPGA versus BSA; for 90% reduction in
      PASI, positive predictive value was lower and negative predictive value was
      higher for BSA * sPGA versus BSA. Receiver operating characteristic curve
      analyses identified the most accurate percentage changes in BSA and BSA * sPGA as
      66% and 83% for a 75% reduction in PASI cutoff and 84% and 94% for a 90%
      reduction in PASI, respectively. These results suggest that BSA and BSA * sPGA
      are viable tools for use as a PASI proxy by real-world practitioners and may be
      appropriate measurements for use in clinical practice for treat-to-target
      strategies.

PMID- 29577917
TI  - Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis.
AB  - Cutaneous wounds in adult mammals typically heal by scarring. However, large full
      thickness wounds undergo wound-induced hair follicle neogenesis (WIHN), a form of
      regeneration. Here, we show that WIHN requires transient expression of epidermal
      Msx2 in two phases: the wound margin early and the wound center late. Msx2
      expression is present in the migrating epithelium during early wound healing and
      then presents in the epithelium and mesenchyme later in the wound center. WIHN is
      abrogated in germline and epithelial-specific Msx2 mutant mice. Unlike the full
      length Msx2 promoter, a minimal Msx2 promoter fails activation in the wound
      center, suggesting complex regulation of Msx2 expression. The Msx2 promoter
      binding sites include Tcf/Lef, Jun/Creb, Pax3, and three SMAD sites. However,
      basal epithelial-induced BMP suppression by noggin overexpression did not affect
      WIHN. We propose that Msx2 signaling is required for the epidermis to acquire
      spatiotemporal competence during WIHN. Topologically, hair regeneration dominates
      in the wound center, coinciding with late Msx2 expression. Together, these
      results suggest that intrinsic Msx2 expression supports epithelial competency
      during hair follicle neogenesis. This work provides insight into endogenous
      mechanisms modulating competency of adult epidermal progenitors for mammalian
      ectodermal appendage neogenesis, and offers the target Msx2 for future
      regeneration-promoting therapies.

PMID- 29577920
TI  - IL-21 Attenuates FITC-Induced Contact Hypersensitivity Response via Regulation of
      Dendritic Cell Function.
AB  - IL-21 is mainly produced by activated CD4+ T cells and is involved in the
      activation of immune cells such as T cells and macrophages. In contrast, IL-21
      suppresses dendritic cell maturation. We studied the effect of IL-21 in a mouse
      model of FITC-induced contact hypersensitivity using IL-21 isoform transgenic (IL
      21iso-Tg) mice. Tissue inflammation at 24 hours after elicitation in IL-21iso-Tg
      mice was significantly weaker than that in wild-type mice. In agreement with
      tissue inflammation, recruitment of CD4+ and CD8+ T cells, neutrophils, and
      macrophages into the inflamed tissue was decreased in IL-21iso-Tg mice. In
      addition, both mRNA expression and protein production of inflammatory cytokines
      were lower in IL-21iso-Tg mice. In the skin, T cells were activated at inducible
      skin-associated lymphoid tissue, which is likely a gut-associated lymphoid
      tissue. The mRNA level of CXCL2, an essential chemokine for inducible skin
      associated lymphoid tissue formation, was significantly lower in IL-21iso-Tg
      mice, and histological analysis showed that dendritic cell clustering, a
      preliminary step in inducible skin-associated lymphoid tissue formation, was
      impaired. Our study showed that IL-21 down-regulated inducible skin-associated
      lymphoid tissue formation and reduced contact hypersensitivity response.

PMID- 29577921
TI  - Rigid Plate Fixation Versus Wire Cerclage for Sternotomy After Cardiac Surgery: A
      Meta-Analysis.
AB  - BACKGROUND: Traditionally, wire cerclage has been used to reapproximate the
      sternum after sternotomy. Recent evidence suggests that rigid plate fixation for
      sternal closure may reduce the risk of sternal complications. METHODS: The
      Medline and Embase databases were searched from inception to February 2017 for
      studies that compared rigid plate fixation with wire cerclage for cardiac surgery
      patients undergoing sternotomy. Random effects meta-analysis compared rates of
      sternal complications (primary outcome, defined as deep or superficial sternal
      wound infection, or sternal instability), early mortality, and length of stay
      (secondary outcomes). RESULTS: Three randomized controlled trials (n = 427) and
      five unadjusted observational studies (n = 1,025) met inclusion criteria. There
      was no significant difference in sternal complications with rigid plate fixation
      at a median of 6 months' follow-up (incidence rate ratio 0.51, 95% confidence
      interval [CI]: 0.20 to 1.29, p = 0.15) overall, but a decrease when including
      only patients at high risk for sternal complications (incidence rate ratio 0.23,
      95% CI: 0.06 to 0.89, p = 0.03; two observational studies). Perioperative
      mortality was reduced favoring rigid plate fixation (relative risk 0.40, 95% CI:
      0.28 to 0.97, p = 0.04; four observational studies and one randomized controlled
      trial). Length of stay was similar overall (mean difference -0.77 days, 95% CI: 
      1.65 to +0.12, p = 0.09), but significantly reduced with rigid plate fixation in
      the observational studies (mean difference -1.34 days, 95% CI: -2.05 to -0.63, p
      = 0.0002). CONCLUSIONS: This meta-analysis, driven by the results of unmatched
      observational studies, suggests that rigid plate fixation may lead to reduced
      sternal complications in patients at high risk for such events, improved
      perioperative survival, and decreased hospital length of stay. More randomized
      controlled trials are required to confirm the potential benefits of rigid plate
      fixation for primary sternotomy closure.

PMID- 29577922
TI  - Efficacy and Cost of Awake Thoracoscopy and Video-Assisted Thoracoscopic Surgery
      in the Undiagnosed Pleural Effusion.
AB  - BACKGROUND: The study aim is to compare the diagnostic yield, safety, and cost of
      outpatient awake thoracoscopy (AT) with video-assisted thoracoscopic surgery
      (VATS) pleural biopsy in undiagnosed pleural effusions. METHODS: The diagnostic
      yield of pleural biopsy performed by AT or VATS in patients with undiagnosed
      exudative pleural effusions at a tertiary thoracic surgery center in Canada
      between 2011 and 2015 was retrospectively evaluated. Test sensitivity,
      specificity, positive predictive value, and negative predictive value were
      compared. Procedure safety, hospital length of stay, additional pleural-based
      interventions, and procedure-related costs were compared. RESULTS: Patients
      underwent either AT (n = 78) or VATS (n = 99) during the study period.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were 85%, 100%, 100%, and 79% for AT and 93%, 94%, 99%, and 76% for VATS,
      with no significant difference in diagnostic test performance. There was no
      difference in the rate of major complications (2 AT [2.6%] versus 4 VATS [4.0%],
      p = 0.696), minor complications (14 AT [17.9%] versus 16 VATS [16.2%], p = 0.841)
      or need for additional pleural-based procedures (20 AT [25.6%] versus 18 VATS
      [18.2%], p = 0.270). The VATS was associated with longer median hospital stay
      (VATS 3 days [interquartile range: 1 to 4] versus AT 0 days [interquartile range:
      0 to 1], z = 6.98, p < 0.001) and a higher procedure-related average cost (VATS
      Canadian dollars $7,962 [95% confidence interval: $7,134 to $8,790] versus AT
      Canadian dollars $2,815 [95% confidence interval: $2,010 to $3,620], p < 0.001).
      CONCLUSIONS: Awake thoracoscopy and VATS have similar diagnostic yield and safety
      profiles in the assessment of undiagnosed pleural effusions; however, AT is
      associated with shorter length of stay and lower average per-procedure cost. In
      the appropriate clinical setting, AT may be the diagnostic test of choice.

PMID- 29577923
TI  - Arteriovenous Malformation Presenting as an Infiltrating Mass of the Right
      Ventricle.

PMID- 29577924
TI  - The Society of Thoracic Surgeons 2018 Adult Cardiac Surgery Risk Models: Part 2
      Statistical Methods and Results.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) uses statistical models to
      create risk-adjusted performance metrics for Adult Cardiac Surgery Database
      (ACSD) participants. Because of temporal changes in patient characteristics and
      outcomes, evolution of surgical practice, and additional risk factors available
      in recent ACSD versions, completely new risk models have been developed. METHODS:
      Using July 2011 to June 2014 ACSD data, risk models were developed for operative
      mortality, stroke, renal failure, prolonged ventilation, mediastinitis/deep
      sternal wound infection, reoperation, major morbidity or mortality composite,
      prolonged postoperative length of stay, and short postoperative length of stay
      among patients who underwent isolated coronary artery bypass grafting surgery (n
      = 439,092), aortic or mitral valve surgery (n = 150,150), or combined valve plus
      coronary artery bypass grafting surgery (n = 81,588). Separate models were
      developed for each procedure and endpoint except mediastinitis/deep sternal wound
      infection, which was analyzed in a combined model because of its infrequency. A
      surgeon panel selected predictors by assessing model performance and clinical
      face validity of full and progressively more parsimonious models. The ACSD data
      (July 2014 to December 2016) were used to assess model calibration and to compare
      discrimination with previous STS risk models. RESULTS: Calibration in the
      validation sample was excellent for all models except mediastinitis/deep sternal
      wound infection, which slightly underestimated risk and will be recalibrated in
      feedback reports. The c-indices of new models exceeded those of the last
      published STS models for all populations and endpoints except stroke in valve
      patients. CONCLUSIONS: New STS ACSD risk models have generally excellent
      calibration and discrimination and are well suited for risk adjustment of STS
      performance metrics.

PMID- 29577925
TI  - The Society of Thoracic Surgeons 2018 Adult Cardiac Surgery Risk Models: Part 1
      Background, Design Considerations, and Model Development.
AB  - BACKGROUND: The last published version of The Society of Thoracic Surgeons (STS)
      Adult Cardiac Surgery Database (ACSD) risk models were developed in 2008 based on
      patient data from 2002 to 2006 and have been periodically recalibrated. In
      response to evolving changes in patient characteristics, risk profiles, surgical
      practice, and outcomes, the STS has now developed a set of entirely new risk
      models for adult cardiac surgery. METHODS: New models were estimated for isolated
      coronary artery bypass grafting surgery (CABG [n = 439,092]), isolated aortic or
      mitral valve surgery (n = 150,150), and combined valve plus CABG procedures (n =
      81,588). The development set was based on July 2011 to June 2014 STS ACSD data;
      validation was performed using July 2014 to December 2016 data. Separate models
      were developed for operative mortality, stroke, renal failure, prolonged
      ventilation, reoperation, composite major morbidity or mortality, and prolonged
      or short postoperative length of stay. Because of its low occurrence rate, a
      combined model incorporating all operative types was developed for deep sternal
      wound infection/mediastinitis. RESULTS: Calibration was excellent except for the
      deep sternal wound infection/mediastinitis model, which slightly underestimated
      risk because of higher rates of this endpoint in the more recent validation data;
      this will be recalibrated in each feedback report. Discrimination (c-index) of
      all models was superior to that of 2008 models except for the stroke model for
      valve patients. CONCLUSIONS: Completely new STS ACSD risk models have been
      developed based on contemporary patient data; their performance is superior to
      that of previous STS ACSD models.

PMID- 29577926
TI  - Type A Aortic Dissection After the Ross Procedure.
AB  - We describe a case of type A aortic dissection in a 25-year-old woman who had
      undergone a Ross procedure for aortic valve endocarditis 13 years previously. She
      was pregnant and noted to have significant enlargement of the aortic root during
      the latter portion of the third trimester of her pregnancy. An echocardiogram
      after delivery demonstrated new aortic valve insufficiency in addition to an
      aortic root diameter of 6.5 cm. A computed tomography angiogram demonstrated a
      type A aortic dissection involving only the very proximal portion of the
      ascending aorta. At operation, the dissection was found to be limited to the
      pulmonary autograft. This was repaired using a valve-sparing technique. Her
      postoperative course was uneventful, and the aortic valve has shown only trace
      insufficiency at 3 years of follow-up.

PMID- 29577927
TI  - Influence of Diabetes Mellitus on Outcomes in Patients After Left Ventricular
      Assist Device Implantation.
AB  - BACKGROUND: Despite previous studies, the mortality risk of patients with
      diabetes mellitus after left ventricular assist device (LVAD) implant remains
      unclear. In addition, the relationship between the degree of glycemic control and
      long-term mortality risk in LVAD patients with diabetes has not been established.
      METHODS: Ninety-five nondiabetic patients and 96 diabetic patients from the
      University of Rochester Medical Center who received a HeartMate II (Thoratec,
      Pleasanton, CA) continuous-flow LVAD between May 2008 and June 2014 were included
      in this study. The primary outcome was all-cause mortality. Secondary outcomes
      included rates of infection, neurologic dysfunction, renal dysfunction, and
      rehospitalization. Kaplan-Meier survival analyses and Cox models were utilized.
      RESULTS: During follow-up, 32 diabetic patients (33%) and 15 nondiabetic patients
      (16%) died after LVAD implantation. Cumulative probability of death was higher
      for diabetic patients when compared with nondiabetic patients (42% versus 21% at
      3 years, p = 0.013). There were no significant differences in overall rates of
      infection, neurologic dysfunction, and rehospitalization between the two groups.
      However, after an initial secondary outcome event, diabetic patients continued to
      have a higher mortality rate when compared with nondiabetic patients. There was
      no statistically significant difference in the risk of death between diabetic
      patients with pre-LVAD hemoglobin A1c less than 7.0% and diabetic patients with
      pre-LVAD hemoglobin A1c 7.0% or greater (hazard ratio 1.71, 95% confidence
      interval: 0.72 to 4.08, p = 0.223). CONCLUSIONS: Diabetic patients who underwent
      LVAD implantation had a higher risk of death compared with nondiabetic patients.
      Adverse event rates did not differ between the two groups. Finally, the degree of
      glycemic control in diabetic patients before LVAD was not found to influence
      mortality.

PMID- 29577928
TI  - Pleural Coating by 50% Glucose Solution Reduces Postoperative Recurrence of
      Spontaneous Pneumothorax.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery is the standard procedure for
      treatment of spontaneous pneumothorax. However, postoperative recurrence is
      relatively common even if an absorbable covering sheet is used for reinforcement
      of the visceral pleura. Injection of a high concentration glucose solution to the
      thoracic cavity was recently reported to be effective in stopping postoperative
      air leakage or as a prophylactic procedure to prevent postoperative recurrence of
      spontaneous pneumothorax. Therefore, we used 50 mL of a 50% glucose solution for
      pleural coating (GPC) on an absorbable sheet intraoperatively to prevent
      postoperative recurrence of spontaneous pneumothorax. This is a retrospective
      study, and patient backgrounds are heterogeneous. We evaluated the feasibility of
      GPC using propensity scores to adjust for heterogeneity in their backgrounds.
      METHODS: Between January 2010 and December 2017, 376 patients who underwent video
      assisted thoracoscopic surgery, with or without GPC, were evaluated. The GPC
      group consisted of 106 patients, and the non-GPC group consisted of 270. We
      analyzed the factors preventing postoperative recurrence of spontaneous
      pneumothorax by univariate analysis and Cox regression analysis with or without
      propensity score matching. RESULTS: Univariate analysis revealed age of 25 or
      older, smoking habit, no history of an ipsilateral operation, and GPC were
      significant factors preventing postoperative recurrence. GPC significantly
      prevented postoperative recurrence as shown by Cox regression analysis with
      propensity score matching (hazard ratio, 0.15; p = 0.014) and the inverse
      probability of treatment weighted method (hazard ratio, 0.23; p = 0.0038).
      CONCLUSIONS: Intraoperative GPC significantly reduced the postoperative
      recurrence rate of spontaneous pneumothorax.

PMID- 29577929
TI  - Giant Cell Tumor of Bone Presenting as Left Posteromedial Chest Wall Tumor.
AB  - Giant cell tumor is a relatively uncommon bone tumor rarely originating from the
      chest wall. Given its proximity to vital structures in the thoracic cavity,
      treatment options may be challenging. We report the case of a patient with a
      giant cell tumor of the posterolateral chest wall with invasion of the thoracic
      spine treated with neoadjuvant denosumab, followed by surgical resection.

PMID- 29577930
TI  - Need for Permanent Pacemaker After Surgical Aortic Valve Replacement Reduces Long
      Term Survival.
AB  - BACKGROUND: Permanent pacemaker (PPM) implantation has been touted as an
      inconsequential complication after transcatheter aortic valve replacement. As
      transcatheter aortic valve replacement moves to lower risk patients, the long
      term implications remain poorly understood; therefore, we evaluated the long-term
      outcomes of pacemaker for surgical aortic valve replacement patients. METHODS: A
      total of 2,600 consecutive patients undergoing surgical aortic valve replacement
      over the past 15 years were reviewed using The Society of Thoracic Surgeons (STS)
      institutional database and Social Security death records. Patients were
      stratified by placement of a PPM within 30 days of surgery. The impact of PPM
      placement on long-term survival was assessed by Kaplan-Meier analysis and risk
      adjusted survival by Cox proportional hazards modeling. RESULTS: A total of 72
      patients (2.7%) required PPM placement postoperatively. Patients requiring PPM
      had more postoperative complications, including atrial fibrillation (43.1% versus
      27.0%, p = 0.003), prolonged ventilation (16.7% versus 5.7%, p < 0.0001), and
      renal failure (12.5% versus 4.6%, p = 0.002). These led to greater resource
      utilization including longer intensive care unit stay (89 versus 44 hours, p <
      0.0001) and hospital length of stay (9 versus 6 days, p < 0.0001), and higher
      inflation-adjusted hospital cost ($81,000 versus $47,000, p < 0.0001). Median
      follow-up was 7.5 years, and patients requiring PPM had significantly worse long
      term survival (p = 0.02), even after risk adjustment with STS predicted risk of
      mortality (hazard ratio 1.48, p = 0.02). CONCLUSIONS: The need for PPM after
      aortic valve replacement independently reduces long-term survival. The rate of
      PPM placement after surgical aortic valve replacement remains very low but
      dramatically increases resource utilization. As transcatheter aortic valve
      replacement expands to low-risk patients, the impact of PPM placement on long
      term survival warrants close monitoring.

PMID- 29577931
TI  - New Screening Techniques in Barrett's Esophagus: Great Ideas or Great Practice?

PMID- 29577932
TI  - Looking for the right mate in diploid species: How does genetic dominance affect
      the spatial differentiation of a sexual trait?
AB  - Divergence between populations for a given trait can be driven by sexual
      selection, interacting with migration behaviour. Mating preference for different
      phenotypes may lead to specific migration behaviour, with departures from
      populations where the preferred trait is rare. Such preferences can then trigger
      the emergence and persistence of differentiated populations, even without any
      local adaptation. However the genetic architecture underlying the trait targeted
      by mating preference may have a profound impact on population divergence. In
      particular, dominance between alleles encoding for divergent phenotypes can
      interfere with the differentiation process. Using a diploid model of a trait
      determining both mating success and migration rate, we explored differentiation
      between two connected populations, assuming either co-dominance or strict
      dominance between alleles. The model assumes that individuals prefer mating with
      partners displaying the same phenotype and therefore tend to move to the other
      population when their own phenotype is rare. We show that the emergence of
      differentiated populations in this diploid moded is limited as compared to
      results obtained with the same model assuming haploidy. When assuming co
      dominance, differentiation arises only when migration is limited compared to the
      strength of the preference. Such differentiation is less dependent on migration
      when assuming strict dominance between haplotypes. Dominant alleles frequently
      invade populations because their phenotype is more frequently expressed,
      resulting in higher local mating success and a rapid decrease in migration.
      However, depending on the initial distribution of alleles, this advantage
      associated with dominance (i.e. Haldane's sieve) may lead to fixation of the
      dominant allele throughout both populations. Depending on the initial
      distribution of heterozygotes in the two populations, persistence of
      polymorphisms within populations can also occur because heterozygotes displaying
      the predominant phenotype benefit from high mating success. Altogether, our
      results highlight that heterozygotes' behaviour has a strong impact on population
      differentiation and highlight the need for diploid models of differentiation and
      speciation driven by sexual selection.

PMID- 29577934
TI  - Selective Spatiotemporal Vulnerability of Central Nervous System Neurons to
      Pathologic TAR DNA-Binding Protein 43 in Aged Transgenic Mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and fatal disease
      characterized by muscular atrophy because of loss of upper and lower motor
      neurons. Histopathologically, most patients with ALS have abnormal cytoplasmic
      accumulation and aggregation of the nuclear RNA-regulating protein TAR DNA
      binding protein 43 (TDP-43). Pathogenic mutations in the TARDBP gene that encode
      TDP-43 have been identified in familial ALS. We have previously reported
      transgenic mice with neuronal expression of human TDP-43 carrying the pathogenic
      A315T mutation (iTDP-43A315T mice), presenting with early-onset motor deficits in
      adolescent animals. Here, we analyzed aged iTDP-43A315T mice, focusing on the
      spatiotemporal profile and progression of neurodegeneration in upper and lower
      motor neurons. Magnetic resonance imaging and histologic analysis revealed a
      differential loss of upper motor neurons in a hierarchical order as iTDP-43A315T
      mice aged. Furthermore, we report progressive gait problems, profound motor
      deficits, and muscle atrophy in aged iTDP-43A315T mice. Despite these deficits
      and TDP-43 pathologic disorders in lower motor neurons, stereological analysis
      did not show cell loss in spinal cords. Taken together, neuronal populations in
      aging iTDP-43A315T mice show differential susceptibility to the expression of
      human TDP-43A315T.

PMID- 29577935
TI  - Parathyroid Hormone-Like Hormone Induces Epithelial-to-Mesenchymal Transition of
      Intestinal Epithelial Cells by Activating the Runt-Related Transcription Factor
      2.
AB  - Epithelial-to-mesenchymal transition (EMT) is a key contributor to fibroblast
      activation in fibrosis of multiple organs, including the intestine. Parathyroid
      hormone-like hormone (PTHLH) is an important factor in renal fibrosis and
      regulates several processes, including EMT. Herein, we investigated the role of
      PTHLH-induced EMT in intestinal fibrosis associated with Crohn disease. The
      expression levels of the EMT-related proteins, PTHLH, and parathyroid hormone
      receptor 1 (PTH1R) in intestinal tissues were determined by immunohistochemistry,
      and our results revealed that PTHLH and PTH1R were significantly elevated and
      associated with EMT marker expression. Moreover, neutralizing PTH1R and
      antagonizing PTHLH bioactivity prevented transforming growth factor-beta1-induced
      EMT. PTH1R can propagate the protein kinase A (PKA) signal and activate
      downstream nuclear transcription factors, including runt-related transcription
      factor 2 (Runx2). In addition, lentiviral vector-PTHLH-treated mice were highly
      sensitive to 2,4,6-trinitrobenzene sulfonic acid, and analysis of the PTHLH-PTH1R
      axis revealed the involvement of PKA-Runx2 in PTHLH-induced EMT. Our results
      indicate that PTHLH triggered EMT in intestinal epithelial cells through the PKA
      Runx2 pathway, which might serve as a therapeutic target for intestinal fibrosis
      in Crohn disease.

PMID- 29577933
TI  - Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and
      Metastatic Prostate Cancer.
AB  - Antibodies targeting the programmed cell death protein 1/programmed death-ligand
      1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD
      L1 protein expression is a clinically validated predictive biomarker of response
      for such therapies. Prior studies evaluating the expression of PD-L1 in primary
      prostate cancers have reported highly variable rates of PD-L1 positivity. In
      addition, limited data exist on PD-L1 expression in metastatic castrate-resistant
      prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by
      immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large
      and representative cohort of primary prostate cancers and prostate cancer
      metastases. The study included 539 primary prostate cancers comprising 508 acinar
      adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and
      a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar
      adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining.
      Increased levels of PD-L1 expression were noted in 42.9% of small-cell
      carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In
      conclusion, in this comprehensive evaluation of PD-L1 expression in prostate
      cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates
      of PD-L1 positivity were observed in mCRPC. These results will be important for
      the future clinical development of programmed cell death protein 1/PD-L1
      targeting therapies in prostate cancer.

PMID- 29577936
TI  - Possible Involvement of Human Mast Cells in the Establishment of Pregnancy via
      Killer Cell Ig-Like Receptor 2DL4.
AB  - The involvement of mast cells in the establishment of pregnancy is unclear.
      Herein, we found that human mast cells are present in the decidual tissues of
      parous women and expressed a human-specific protein killer cell Ig-like receptor
      (KIR) 2DL4, a receptor for human leukocyte antigen G expressed on human
      trophoblasts. In contrast, decreased numbers of decidual mast cells and reduced
      KIR2DL4 expression were observed in these cells of infertile women who had
      undergone long-term corticosteroid treatment. Co-culture of the human mast cell
      line, LAD2, and human trophoblast cell line, HTR-8/SVneo, accelerated the
      migration and tube formation of HTR-8/SVneo cells in a KIR2DL4-dependent manner.
      These observations suggest the possible involvement of human mast cells in the
      establishment of pregnancy via KIR2DL4 and that long-term corticosteroid
      treatment may cause infertility by influencing the phenotypes of decidual mast
      cells.

PMID- 29577937
TI  - Hepatitis C Virus Mimics Effects of Glypican-3 on CD81 and Promotes Development
      of Hepatocellular Carcinomas via Activation of Hippo Pathway in Hepatocytes.
AB  - Glypican (GPC)-3 is overexpressed in hepatocellular carcinomas (HCCs). GPC3 binds
      to CD81. Forced expression of CD81 in a GPC3-expressing HCC cell line caused
      activation of Hippo, a decrease in ezrin phosphorylation, and a decrease in yes
      associated protein (YAP). CD81 is also associated with hepatitis C virus (HCV)
      entry into hepatocytes. Activation of CD81 by agonistic antibody causes
      activation of tyrosine-protein kinase SYK (SYK) and phosphorylation of ezrin, a
      regulator of the Hippo pathway. In cultures of normal hepatocytes, CD81 agonistic
      antibody led to enhanced phosphorylation of ezrin and an increase in nuclear YAP.
      HCV E2 protein mimicked GPC3 and led to enhanced Hippo activity and decreased YAP
      in cultured normal human hepatocytes. HCC tissue microarray revealed a lack of
      expression of CD81 in most HCCs, rendering them insusceptible to HCV infection.
      Activation of CD81 by agonistic antibody suppressed the Hippo pathway and
      increased nuclear YAP. HCV mimicked GPC3, causing Hippo activation and a decrease
      in YAP. HCV is thus likely to enhance hepatic neoplasia by acting as a promoter
      of growth of early CD81-negative neoplastic hepatocytes, which are resistant to
      HCV infection, and thus have a proliferative advantage to clonally expand as they
      participate in compensatory regeneration for the required maintenance of 100% of
      liver weight (hepatostat).

PMID- 29577938
TI  - HS218 as an FXR antagonist suppresses gluconeogenesis by inhibiting FXR binding
      to PGC-1alpha promoter.
AB  - INTRODUCTION: Farnesoid X receptor (FXR) as a member of nuclear receptor is
      tightly associated with glucose metabolism. Accumulated evidence has addressed
      the potential of FXR antagonist in the treatment of type 2 diabetes mellitus
      (T2DM), although the related mechanisms remain unclear. Here, we determined a
      specific FXR antagonist HS218 (N-benzyl-N-(3-(tert-butyl)-4-hydroxyphenyl)-2,4
      dichlorobenzamide), which exhibited high activities in suppressing
      gluconeogenesis and ameliorating glucose homeostasis in db/db and HFD/STZ-induced
      T2DM mice. We would like to investigate the mechanisms underlying FXR antagonism
      in the regulation of gluconeogenesis by using HS218 as a probe. METHODS: HS218
      was evaluated by glucose output assay. Binding affinity of HS218 to the ligand
      binding domain of FXR (FXR-LBD) was detected by Surface Plasmon Resonance (SPR)
      technology-based Biacore and fluorescence quenching assays. Mammalian one-hybrid
      and transactivation assays were carried out to detect the antagonistic effect of
      HS218 on FXR. Real-time PCR assay was performed to measure the expressions of FXR
      target and gluconeogenic genes. Anti-diabetic efficiencies of HS218 were
      determined in db/db and HFD/STZ-induced T2DM mice. Assays by promoter 5'-deletion
      analysis and Chromatin immunoprecipitation (ChIP) were performed to detect the
      binding of FXR to peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) promoter. Western blot assay was used to determine the
      protein level in either cells or the liver tissues of mice. RESULTS: We
      determined that HS218 as a new FXR specific antagonist could FXR-dependently
      suppress gluconeogenesis in mouse primary hepatocytes, and effectively improve
      glucose homeostasis in db/db and HFD/STZ-induced T2DM mice. HS218 decreased
      gluconeogenesis by inhibiting the FXR-induced increase in the promoter activity
      of the key gluconeogenic gene PGC-1alpha, leading to the repression of PGC-1alpha
      and its target gene peroxisome proliferator-activated receptor alpha (PPARalpha).
      CONCLUSIONS: To our knowledge, our work might be the first report on the
      mechanism underlying FXR antagonist in the regulation of gluconeogenesis, and all
      results have also highlighted the potential of HS218 in the treatment of T2DM.

PMID- 29577939
TI  - Trends in vanadium neurotoxicity.
AB  - Vanadium, atomic number 23, is a transition metal widely distributed in nature.
      It is a major contaminant of fossil fuels and is widely used in industry as
      catalysts, in welding, and making steel alloys. Over the years, vanadium
      compounds have been generating interests due to their use as therapeutic agents
      in the control of diabetes, tuberculosis, and some neoplasms. However, the
      toxicity of vanadium compounds is well documented in literature with occupational
      exposure of workers in vanadium allied industries, environmental pollution from
      combustion of fossil fuels and industrial exhausts receiving concerns as major
      sources of toxicity and a likely predisposing factor in the aetiopathogenesis of
      neurodegenerative diseases. A lot has been done to understand the neurotoxic
      effects of vanadium, its mechanisms of action and possible antidotes. Sequel to
      our review of the subject in 2011, this present review is to detail the recent
      insights gained in vanadium neurotoxicity.

PMID- 29577940
TI  - Vascular architecture in free flaps: Analysis of vessel morphology and
      morphometry in murine free flaps.
AB  - The aim of this study was to analyze the development of vascular architecture as
      well as vascular morphometry and morphology of anastomosed microvascular free
      flaps. Free pectoral skin flaps were raised in 25 rats and anastomosed to the
      femoral vessels in the groin region. CD31 immunohistology was performed after 3,
      7 and 12 d (each 5 animals each) to analyze microvessel density (MVD),
      microvessel area (MVA) and microvessel size (MVS). Microvascular corrosion
      casting was performed after 7 and 12 d (5 animals each) to analyze vessel
      diameter (VD), intervascular distance (IVD), interbranching distance (IBD), and
      branching angle (BA). Further on, sprout and pillar density as hallmarks of
      sprouting and intussusceptive angiogenesis were analyzed. Pectoral skin isles
      from the contralateral side served as controls. A significantly increased MVD was
      found after 7 and 12 d (p each <0.001). MVA was significantly increased after 3,
      7 and 12 d (p each <0.001) and a significantly increased MVS was analyzed after 3
      and 7 d (p each <0.001). VD and IVD were significantly increased after 7 and 12 d
      (p each <0.001). For IBD, a significantly increase was measured after 7 d (p <
      0.001). For IBA, sprout and pillar density, no significant differences were found
      (p each >=0.05). Significant changes in the vascular architecture of free flaps
      after successful microvascular anastomosis were seen. Since there was no evidence
      for sprout and pillar formation within the free flaps, the increased MVD and flap
      revascularization might be induced by the receiving site.

PMID- 29577941
TI  - How and why do gastrointestinal peptides influence food intake?
AB  - Despite the ability of some gastrointestinal hormones to reliably reduce meal
      size when administered prior to a meal, it is not understood why the repeated
      administration or genetic knockout of these hormones appear largely ineffective
      in reducing food intake and body weight. Here, we review evidence that the
      ability of GI peptides such as cholecystokinin (CCK) to elicit satiation is a
      consequence of prior learning. Evidence includes first, that the ability of some
      of these signals to modify food intake depends upon past experience and is
      malleable with new experience. Additionally, the ability of CCK and other gut
      signals to reduce food intake may not be hard-wired; i.e., any so-called
      "satiation" signal that reduces food intake in a single-meal situation may not
      continue to do so over repeated trials. The individual will respond to the signal
      only so long as it provides reliable information about caloric content. If a
      particular signal becomes unreliable, the individual will rely on other signals
      to end meals. Thus, gut peptides/hormones have important metabolic effects such
      as mediating absorption, digestion, and many aspects of the distribution of
      ingested nutrients throughout the body; and, if they have been reliably
      associated with natural stimuli that mediate satiation, they also inform
      behavior.

PMID- 29577942
TI  - Emodin protects hyperglycemia-induced injury in PC-12 cells by up-regulation of
      miR-9.
AB  - BACKGROUND: Diabetic foot is a severe complication of diabetes mellitus, mainly
      caused by diabetic peripheral neuropathy. The objective of this study was to
      investigate the function of emodin (a neuroprotective agent reported previously)
      in diabetic peripheral neuropathy. METHODS: A neuron-like cell line PC-12 was
      subjected with high level glucose, before which emodin was applied to treat
      cells. The expression of miR-9 in cell was overexpressed or suppressed by miRNA
      transfection. Thereafter, cell viability, apoptosis and autophagy were assessed,
      respectively. RESULTS: High glucose exhibited cytotoxicity in PC-12 cells. Emodin
      protected PC-12 cells against high glucose-induced apoptosis and viability
      impairment. These observations were coupled with the down-regulations of p21,
      p16, Bax, cleaved caspase-3 and -9, and the up-regulations of CyclinD1 and Bcl-2.
      Additionally, high glucose-induced autophagy was alleviated by emodin, as Beclin
      1 was down-regulated, p62 was up-regulated, and the conversion of LC3-I to LC3-II
      was decreased. miR-9 was highly expressed in response to emodin treatment. More
      interestingly, the protective actions of emodin on high glucose-induced injury
      were reversed by miR-9 suppression. Also, the activation of PI3K/AKT signaling
      and deactivation of NF-kappaB signaling induced by emodin were recovered by miR-9
      suppression. CONCLUSION: Emodin protected PC-12 cells against high glucose
      induced apoptosis and autophagy. The neuroprotective activities might be realized
      by up-regulation of miR-9, and modulation of PI3K/AKT and NF-kappaB signaling
      pathways.

PMID- 29577943
TI  - Evidence-based adverse outcome pathway approach for the identification of BPA as
      en endocrine disruptor in relation to its effect on the estrous cycle.
AB  - Proper cyclicity is essential to reach successful optimal fertility. In rats and
      mice, BPA exposure is repeatedly and reliably reported to show an adverse effect
      on the estrous cycle after exposures at different life stages. In humans, a
      possible association between modifications of menstrual cycle characteristics
      (e.g. length of the cycle, duration of menstrual bleeding) and sub-fecundity or
      spontaneous abortion has been observed. Alterations of ovarian cyclicity can
      therefore be definitely considered as an adverse health outcome. As a
      prerequisite for the EU REACH regulation to identify a substance as an endocrine
      disruptor and a SVHC,1 the proof has to be established that the substance can
      have deleterious health effects resulting from an endocrine mode of action. This
      review provides an overview of the currently available data allowing to conclude
      that the adverse effects of BPA exposure on ovarian cyclicity is mediated by an
      endocrine mode of action.

PMID- 29577944
TI  - Downregulation of plasma SELENBP1 protein in patients with recent-onset
      schizophrenia.
AB  - Upregulation of selenium binding protein 1 (SELENBP1) mRNA expression has been
      reported in schizophrenia, primarily in the dorsolateral prefrontal cortex.
      However, peripheral blood studies are limited and results are inconsistent. In
      this study, we examined SELENBP1 mRNA expression in whole blood and protein
      expression in plasma from patients with recent-onset schizophrenia (n = 30),
      treatment-resistant schizophrenia (n = 71) and healthy controls (n = 57). We also
      examined the effects of SELENBP1 genetic variation on gene and protein
      expression. We found lower SELENBP1 plasma protein levels in patients with recent
      onset schizophrenia (p = 0.042) but not in treatment-resistant schizophrenia (p =
      0.81). Measurement of peripheral mRNA levels showed no difference between
      treatment-resistant schizophrenia and healthy controls (p = 0.234) but clozapine
      plasma levels (p = 0.036) and duration of illness (p = 0.028) were positively
      correlated with mRNA levels. Genetic variation was not associated with mRNA or
      protein expression. Our data represent the first peripheral proteomic study of
      SELENBP1 in schizophrenia and suggest that plasma SELENBP1 protein is
      downregulated in patients with recent-onset schizophrenia.

PMID- 29577945
TI  - Effect of experience, equipment and fire actions in psychophysiological response
      and memory of soldiers in actual underground operations.
AB  - The present study aimed to analyze the effect of underground operations on the
      psychophysiological and memory response of soldiers taking into consideration
      experience, the use of nocturne vision systems and previous combat actions on the
      psychophysiological response. Seventy participants were recruited and divided in
      four groups, three experimental groups with different experimental conditions,
      SNFV (Soldiers No-Fire Night-Vision), SFV (Soldiers Fire Night-Vision), SNFNV
      (Soldiers No-Fire No Night-Vision), and one control group, CNFV (Control No-Fire
      Night-Vision). We analyzed modifications in psychophysiological and memory
      response pre and post an underground operation. The underground operation
      produced a significant increase (p < 0.05) in blood lactate, blood oxygen
      saturation, rated perceived exertion, heart rate, cognitive and somatic anxiety
      and sympathetic modulation in all groups. Groups with higher stress values scored
      higher incorrect items in the memory post mission questionnaire. The higher
      psychophysiological activation correlated positively with cognitive impairment
      and lower memory. We concluded that an underground operation produced an increase
      in psychophysiological activation and a negative effect on memory, being
      modulated by previous training and experience. The lack of special equipment as
      night vision systems in underground operations induced similar stress response
      than prior combat actions, decreasing conciseness of time.

PMID- 29577946
TI  - Specificity of spontaneous EEG associated with different levels of cognitive and
      communicative dysfunctions in children.
AB  - This study aimed to reveal electrophysiological markers of communicative and
      cognitive dysfunctions of different severity in children with autism spectrum
      disorder (ASD). Eyes-opened electroencephalograms (EEGs) of 42 children with ASD,
      divided into two groups according to the severity of their communicative and
      cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and
      70 age-matched controls aged 4-9 years were examined by means of spectral and
      group independent component (gIC) analyses. A predominance of theta and beta EEG
      activity in both groups of children with ASD compared to the activity in the
      control group was found in the global gIC together with a predominance of beta
      EEG activity in the right occipital region. The quantity of local gICs with
      enhanced slow and high-frequency EEG activity (within the frontal, temporal, and
      parietal cortex areas) in children 4-9 years of age might be considered a marker
      of cognitive and communicative dysfunction severity.

PMID- 29577947
TI  - RIFM fragrance ingredient safety assessment cyclohexanecarboxylic acid, CAS
      Registry Number 98-89-5.

PMID- 29577948
TI  - l-Arginine induces antioxidant response to prevent oxidative stress via
      stimulation of glutathione synthesis and activation of Nrf2 pathway.
AB  - Arginine is a conditionally essential amino acid. To elucidate the influence of l
      arginine on the activation of endogenous antioxidant defence, male Wistar rats
      were orally administered daily with l-arginine at different levels of 25, 50, 100
      mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities
      and glutathione (GSH) contents in the plasma and in the liver were uniformly
      enhanced with the increasing consumption of l-arginine, whereas the oxidative
      stress was effectively suppressed by l-arginine treatment. After 14 days feeding,
      the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced
      by increasing l-arginine intake, resulting that the nuclear factor Nrf2 was
      activated. Upon activation of Nrf2, the expressions of antioxidant responsive
      element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT,
      SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, indicating an upward
      trend in antioxidant capacity uniformly with the increasing consumption of l
      arginine. The present study demonstrates that the supplementation of l-arginine
      stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation
      of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the
      availability of l-arginine is a critical factor to suppress oxidative stress and
      induce an endogenous antioxidant response.

PMID- 29577949
TI  - Quantification of ligand density and stoichiometry on the surface of liposomes
      using single-molecule fluorescence imaging.
AB  - Despite the longstanding existence of liposome technology in drug delivery
      applications, there have been no ligand-directed liposome formulations approved
      for clinical use to date. This lack of translation is due to several factors, one
      of which is the absence of molecular tools for the robust quantification of
      ligand density on the surface of liposomes. We report here for the first time the
      quantification of proteins attached to the surface of small unilamellar liposomes
      using single-molecule fluorescence imaging. Liposomes were surface-functionalized
      with fluorescently labeled human proteins previously validated to target the
      cancer cell surface biomarkers plasminogen activator inhibitor-2 (PAI-2) and
      trastuzumab (TZ, Herceptin(r)). These protein-conjugated liposomes were
      visualized using a custom-built wide-field fluorescence microscope with single
      molecule sensitivity. By counting the photobleaching steps of the fluorescently
      labeled proteins, we calculated the number of attached proteins per liposome,
      which was 11 +/- 4 proteins for single-ligand liposomes. Imaging of dual-ligand
      liposomes revealed stoichiometries of the two attached proteins in accordance
      with the molar ratios of protein added during preparation. Preparation of PAI
      2/TZ dual-ligand liposomes via two different methods revealed that the post
      insertion method generated liposomes with a more equal representation of the two
      differently sized proteins, demonstrating the ability of this preparation method
      to enable better control of liposome protein densities. We conclude that the
      single-molecule imaging method presented here is an accurate and reliable
      quantification tool for determining ligand density and stoichiometry on the
      surface of liposomes. This method has the potential to allow for comprehensive
      characterization of novel ligand-directed liposomes that should facilitate the
      translation of these nanotherapies through to the clinic.

PMID- 29577950
TI  - Primary deuterium kinetic isotope effects prolong drug release and polymer
      biodegradation in a drug delivery system.
AB  - We have developed a chemically-controlled drug delivery system in which a drug is
      covalently attached via a carbamate to hydrogel microspheres using a beta
      eliminative linker; rate-determining proton removal from a CH bond adjacent to an
      electron withdrawing group results in a beta-elimination to cleave the carbamate
      and release the drug. After subcutaneous injection of the hydrogel-drug
      conjugate, the drug is slowly released into the systemic circulation and acquires
      an elimination t1/2,beta that matches the t1/2 of linker cleavage. A similar beta
      eliminative linker with a slower cleavage rate is installed into crosslinks of
      the polymer to trigger gel degradation after drug release. We have now prepared
      beta-eliminative linkers that contain deuterium in place of the hydrogen whose
      removal initiates cleavage. In vitro model systems of drug release and degelation
      show large primary deuterium kinetic isotope effects of kH/kD ~ 2.5 to 3.5. Using
      a deuterated linker to attach the peptide octreotide to hydrogel-microspheres,
      the in vivo t1/2,beta of the drug was increased from ~1.5 to 4.5 weeks in the
      rat. Similarly, the in vivo time to biodegradation of hydrogels with deuterium
      containing crosslinks could be extended ~2.5-fold compared to hydrogen-containing
      counterparts. Thus, the use of primary deuterium kinetic isotope effects in a
      single platform technology can control rates of beta-elimination reactions in
      drug release and polymer biodegradation rates.

PMID- 29577951
TI  - Interaction of porcine reproductive and respiratory syndrome virus major envelope
      proteins GP5 and M with the cellular protein Snapin.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is characterized
      by abortions in pregnant sows and respiratory disease, particularly in young
      pigs. The causative agent is porcine reproductive and respiratory syndrome virus
      (PRRSV), a member of the arterivirus family. GP5 and M are the major envelope
      proteins encoded by PRRSV. To further characterize these two viral proteins, a
      yeast two-hybrid approach was utilized to identify interacting partners of PRRSV
      GP5 and M proteins. METHODS: Interacting partners of PRRSV GP5 and M were
      identified using a porcine macrophage cDNA library yeast two-hybrid screen.
      Subsequently, the interactions between PRRSV GP5/M and the cellular protein
      Snapin were mapped using truncated versions of the GP5 and M proteins in a yeast
      two-hybrid assay to localize the interactions. The Snapin gene from the African
      green monkey kidney cell line MARC-145, which is permissive to PRRSV, was cloned
      and sequenced, and compared to porcine Snapin. Cellular Snapin expression was
      reduced in PRRSV-infected cells via Snapin-specific siRNA targeting. RESULTS:
      Here we show that the cellular Snap-Associated Protein (Snapin), an accessory
      protein of the SNARE membrane fusion network and also a member of the BLOC-1
      complex, specifically interacts with GP5 and M. Inhibition of Snapin expression
      via siRNA targeting of Snapin results in the reduction of PRRSV replication.
      CONCLUSIONS: The PRRSV GP5 and M proteins are known to form a heterodimeric
      complex which is important for viral structure and infectivity, and both PRRSV
      proteins can interact with cellular Snapin. Snapin knock-down suggests these
      interactions could be important in the PRRSV lifecycle. GP5 and M proteins may
      interact with Snapin to exploit its roles in intracellular transport and membrane
      fusion.

PMID- 29577952
TI  - Lipid transfer protein isolated from noni seeds displays antibacterial activity
      in vitro and improves survival in lethal sepsis induced by CLP in mice.
AB  - In the present study, we aimed to evaluate the antibacterial activity of a lipid
      transfer protein isolated from Morinda citrifolia L. seeds, named McLTP1, and to
      investigate its effect in the cecal ligation and puncture (CLP) mouse sepsis
      model. Antimicrobial assays revealed that McLTP1 (12.5-800 MUg/mL) significantly
      reduced Staphylococcus aureus (ATCC 6538P and ATCC 14458) and Staphylococcus
      epidermidis (ATCC 12228) planktonic growth, reaching maximal inhibition of
      approximately 50% and 98%, respectively. Furthermore, McLTP1 inhibited biofilm
      formation of both S. aureus strains, achieving percentages ranging from 39.1% to
      69.1% (200-800 MUg/mL) for ATCC 6538P and 34.4%-63% (12.5-800 MUg/mL) for ATCC
      14458. A synergistic interaction between McLTP1 and oxacillin against S. aureus
      and S. epidermidis was also observed, as determined by fractional inhibitory
      concentration indices of 0.18 and 0.38, respectively. McLTP1 showed no
      significant inhibitory effect against Gram-negative bacteria. In the in vivo
      experiments, sepsis was lethal to 83% of the animals, 72 h after CLP. In
      contrast, 100% of the animals treated with McLTP1 (8 mg/kg) before
      (intraperitoneal injection or oral dose) or after (oral dose) CLP were still
      alive 3 days later. In addition, oral or intraperitoneal administration of McLTP1
      (8 mg/kg) significantly reduced the body weight loss, fever, leukocytosis, organ
      damage, and the level of inflammatory serum cytokines induced by sepsis. In
      conclusion, McLTP1 could be exploited for its antimicrobial properties, and can
      be considered a potential therapeutic candidate for the management of clinical
      sepsis.

PMID- 29577953
TI  - Synthesis of novel 17-triazolyl-androst-5-en-3-ol epimers via Cu(I)-catalyzed
      azide-alkyne cycloaddition and their inhibitory effect on 17alpha
      hydroxylase/C17,20-lyase.
AB  - The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 17alpha- and
      17beta-azidoandrost-5-en-3beta-ol epimers (3b and 5b) with different terminal
      alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-k and 9a-k). For
      the preparation of 5'-iodo-1',2',3'-triazoles (8m-n and 9m-n), an improved method
      was developed, directly from steroidal azides and terminal alkynes, in reaction
      mediated by CuI and ICl as iodinating agents. Acetolysis and subsequent
      hydrolysis of 8n and 9n yielded 5'-hydroxy-1',2',3'-triazoles 8o and 9o. The
      inhibitory effect of 8a-o, 9a-o, 3, and 5 on rat testicular C17,20-lyase was
      investigated by means of an in vitro radioincubation technique. The results
      revealed that the C-17 epimers of steroidal triazoles influence the C17,20-lyase
      effect. Inhibitors were found only in the 17alpha-triazolyl series (8a-o),
      whereas in the C-17 azide pair the 17beta compound (5b) was more potent.

PMID- 29577954
TI  - Assessment of flow dynamics in retinal and choroidal microcirculation.
AB  - Alterations in ocular blood flow have been implicated in mechanisms that lead to
      vision loss in patients with various ocular disorders such as diabetic
      retinopathy, glaucoma, and age-related macular degeneration. Assessment of
      retinal and choroidal blood flow is also a window to evaluate systemic diseases
      that affect microvasculature. Quantification and qualification of the blood flow
      in the retina and choroid help us understand pathophysiology, stratify disease
      risk, and monitor disease progression in these disorders. Multiple methods are
      used by researchers for assessment of blood flow, but a gold standard is lacking.
      We review commonly used methods, both invasive and noninvasive, for evaluation of
      blood flow, including intravital microscopy, laser Doppler velocimetry, laser
      Doppler flowmetry, laser interferometry, confocal scanning laser Doppler
      flowmetry, laser speckle flowgraphy, Doppler optical coherence tomography, blue
      field entoptic simulation, retinal vessel caliber assessment, optical coherence
      tomography angiography, retinal function imaging, color Doppler imaging, and
      scanning laser ophthalmoscope angiogram. As technology evolves, better evaluation
      of blood flow in various ocular and systemic diseases will likely bring new
      perspectives into clinical practice and translate to better diagnosis and
      treatment.

PMID- 29577955
TI  - Adrenomedullin: Continuing to explore cardioprotection.
AB  - Adrenomedullin (AM), a peptide isolated from an extract of human
      pheochromocytoma, comprises 52 amino acids with an intramolecular disulfide bond
      and amidation at the carboxy-terminus. AM is present in various tissues and
      organs in rodents and humans, including the heart. The peptide concentration
      increases with cardiac hypertrophy, acute myocardial infarction, and overt heart
      failure in the plasma and the myocardium. The principal function of AM in the
      cardiovascular system is the regulation of the vascular tone by vasodilation and
      natriuresis via cyclic adenosine monophosphate-dependent or -independent
      mechanism. In addition, AM may possess unique properties that inhibit aldosterone
      secretion, oxidative stress, apoptosis, and stimulation of angiogenesis,
      resulting in the protection of the structure and function of the heart. The AM
      receptor comprises a complex between calcitonin receptor-like receptor (CLR) and
      receptor activity-modifying protein (RAMP) 2 or 3, and the AM-CLR/RAMP2 system is
      essential for heart development during embryogenesis. Small-scale clinical trials
      have proven the efficacy and safety of recombinant AM peptide therapy for heart
      failure. Gene delivery and a modified AM peptide that prolongs the half-life of
      the native peptide could be an innovative method to improve the efficacy and
      benefit of AM in clinical settings. In this review, we focus on the
      pathophysiological roles of AM and its receptor system in the heart and describe
      the advances in AM and proAM-derived peptides as diagnostic biomarkers as well as
      the therapeutic application of AM and modified AM for cardioprotection.

PMID- 29577956
TI  - Toll immune signal activates cellular immune response via eicosanoids.
AB  - Upon immune challenge, insects recognize nonself. The recognition signal will
      propagate to nearby immune effectors. It is well-known that Toll signal pathway
      induces antimicrobial peptide (AMP) gene expression. Eicosanoids play crucial
      roles in mediating the recognition signal to immune effectors by enhancing
      humoral immune response through activation of AMP synthesis as well as cellular
      immune responses, suggesting a functional cross-talk between Toll and eicosanoid
      signals. This study tested a cross-talk between these two signals. Two signal
      transducing factors (MyD88 and Pelle) of Toll immune pathway were identified in
      Spodoptera exigua. RNA interference (RNAi) of either SeMyD88 or SePelle
      expression interfered with the expression of AMP genes under Toll signal pathway.
      Bacterial challenge induced PLA2 enzyme activity. However, RNAi of these two
      immune factors significantly suppressed the induction of PLA2 enzyme activity.
      Furthermore, RNAi treatment prevented gene expression of cellular PLA2.
      Inhibition of PLA2 activity reduced phenoloxidase activity and subsequent
      suppression in cellular immune response measured by hemocyte nodule formation.
      However, immunosuppression induced by RNAi of Toll signal molecules was
      significantly reversed by addition of arachidonic acid (AA), a catalytic product
      of PLA2. The addition also significantly reduced the enhanced fungal
      susceptibility of S. exigua treated by RNAi against two Toll signal molecules.
      These results indicate that there is a cross-talk between Toll and eicosanoid
      signals in insect immunity.

PMID- 29577957
TI  - Aluminum is a powerful adjuvant in teleost fish despite failing to induce
      interleukin-1beta release.
AB  - Although aluminum salts (Alum) have been extensively used in human vaccination
      for decades, its mechanism of action is controversial. In fish, the use of Alum
      as a vaccine adjuvant is scarce and there are no studies aimed at identifying its
      mechanism of action. In the present study we report that Alum is a powerful
      adjuvant in the gilthead seabream (Sparus aurata L., Sparidae) and the European
      seabass (Dicentrarchus labrax L. Moronidae). Thus, Alum increased the specific
      antibody titers to the model antigen keyhole limpet hemocyanin as the commonly
      used Freund's adjuvant did in both species. In addition, both adjuvants were able
      to increase the transcript levels of the gene encoding the major pro-inflammatory
      mediator interleukin-1beta (Il1b). Strikingly, however, Alum failed to promote
      Il1b release by seabream leukocytes and even impaired Il1b induction, processing
      and release in macrophages. However, it increased NADPH oxidase-dependent
      reactive oxygen species (ROS) production in gilthead seabream leukocytes and
      purified granulocytes. In addition, Alum promoted gilthead seabream leukocyte
      death independently of ROS production and caspases, suggesting that damage
      associated molecular patterns release from dying cells mediate Alum adjuvant
      activity. Our results pave the way for future studies aimed at investigating the
      relevance of danger signals generated by Alum in vivo on its adjuvant activity in
      order to increase our understanding of the mechanisms of action of Alum in fish
      vaccines and to help in the design of new adjuvants for aquaculture.

PMID- 29577958
TI  - The validation & verification of an LC/MS method for the determination of total
      docosahexaenoic acid concentrations in canine blood serum.
AB  - Docosahexaenoic acid (DHA), is an omega 3 fatty acid (n-3 FA) that has been shown
      to play a role in canine growth and physiological integrity and improvements in
      skin and coat condition. However, potential adverse effects of n-3 FA
      specifically, impaired cellular immunity has been observed in dogs fed diets with
      elevated levels of n-3 FA. As such, a safe upper limit (SUL) for total n-3 FAs
      (DHA and EPA) in dogs has been established. Considering this SUL, sensitive
      methods detecting DHA in blood serum as a biomarker when conducting n-3 FA
      supplementation trials involving dogs are required. In this study, an LC-ESI
      MS/MS method of DHA detection in dog serum was validated and verified. Recovery
      of DHA was optimized and parallelism tests were conducted with spiked samples
      demonstrating that the serum matrix did not interfere with quantitation. The
      stability of DHA in serum was also investigated, with -80  degrees C considered
      suitable when storing samples for up to six months. The method was linear over a
      calibration range of 1-500 MUg/mL and precision and accuracy were found to meet
      the requirements for validation. This method was verified in an alternative
      laboratory using a different analytical system and operator, with the results
      meeting the criteria for verification.

PMID- 29577959
TI  - Sirtuin activators and inhibitors: Promises, achievements, and challenges.
AB  - The NAD+-dependent protein lysine deacylases of the Sirtuin family regulate
      various physiological functions, from energy metabolism to stress responses. The
      human Sirtuin isoforms, SIRT1-7, are considered attractive therapeutic targets
      for aging-related diseases, such as type 2 diabetes, inflammatory diseases and
      neurodegenerative disorders. We review the status of Sirtuin-targeted drug
      discovery and development. Potent and selective pharmacological Sirt1 activators
      and inhibitors are available, and initial clinical trials have been carried out.
      Several promising inhibitors and activators have also been described for other
      isoforms. Progress in understanding the mechanisms of Sirtuin modulation by such
      compounds provides a rational basis for further drug development.

PMID- 29577960
TI  - Functional dissociation of temporal processing mechanisms during speech
      production and hand movement: An ERP study.
AB  - Skilled motor actions are mediated by neural mechanisms that incorporate sensory
      feedback for driving or suppressing movement with remarkable temporal precision.
      The predictive coding model proposes that the brain performs this function by
      establishing an internal representation of timing to accelerate movement response
      time. However, it is unclear whether different neural mechanisms are involved in
      temporal processing of movement initiation and cessation. The present study
      examined how temporal information is encoded for initiation and cessation of
      speech and hand movement. Event-related potentials (ERPs) were recorded while
      young healthy subjects performed speech and hand movement initiation and
      cessation in response to temporally predictable and unpredictable visual stimuli.
      We found that predictable stimuli elicited faster movement in both speech and
      hand modalities, with shorter reaction times associated with movement cessation
      compared with initiation. Analysis of ERPs revealed that premotor neural
      activities were significantly attenuated before speech initiation and hand
      movement initiation and cessation for temporally predictable vs. unpredictable
      conditions, but an opposite pattern was observed for speech cessation. In
      addition, we observed that the premotor ERPs were significantly modulated during
      speech initiation vs. cessation, but no such effect was found during hand
      movement. Finally, we found that the premotor ERPs were strongly correlated with
      motor reaction time during movement initiation and cessation for speech and hand
      modalities only in response to temporally predictable stimuli. These findings
      indicate that premotor ERPs reflect a temporal predictive code for planning of
      movement initiation and cessation and highlight functional dissociation of
      temporal processing mechanisms in speech and hand motor systems.

PMID- 29577961
TI  - Sleep-related brain atrophy and disrupted functional connectivity in older
      adults.
AB  - Aging associates with sleep dysfunction as well as brain alterations. However,
      the association between age-related brain alterations and their subjective sleep
      changes is less understood. To address this issue, we recorded T1 weighted
      structural and resting-state functional magnetic resonance imaging from both
      young (n = 62) and older adults (n = 108). In addition, all participants
      completed a battery of psychometric tests, including the Pittsburg Sleep Quality
      Index. We found that the age-related atrophy of cerebral gray matter, hippocampal
      and thalamic volume were associated with subjective sleep decline, and the
      atrophy of cerebral gray matter mediated the age effect on sleep. In addition,
      older adults exhibited decreased functional connectivity within the medial
      temporal lobe subsystem than their young counterparts. Moreover, there is a
      significant positive association between sleep and functional connectivity in
      young but not in older adults. In light of our findings, we suggest a
      neuropathological model in which age-related brain alterations may partially
      explain the well-documented declines in sleep with aging.

PMID- 29577962
TI  - Correlations between donor-specific antibodies and non-adherence with chronic
      active antibody-mediated rejection phenotypes and their impact on kidney graft
      survival.
AB  - Chronic-active antibody-mediated rejection (CAABMR) is associated with poor
      kidney graft survival and has no clear effective treatment. Forty-one cases of
      CAABMR were detected in indication graft biopsies and evaluated according to
      current Banff classification. We investigated the impact of concurrent donor
      specific antibodies (DSA) and their characteristics, together with non-adherence
      regarding immunosuppression on CAABMR histopathological phenotypes and prognosis.
      Twenty-four (59%) patients had detectable DSA at biopsy, with 15 of them being
      considered non-adherent. Graft function at biopsy was similar in DSA (+) and (-)
      patients. DSA (+) patients had significantly higher tubulointerstitial
      inflammation (i and ti) and acute humoral (g+ptc+v+C4d) composite score than DSA
      (-). DSA (+)/non-adherent cases presented additionally with increased
      microvascular inflammation (ptc and v), besides having a distinctively lower ah
      score. C1q DSA strength was higher (P = .046) in non-adherent patients and
      correlated closely with C4d score (P = .002). Lower graft function and ah score,
      higher proteinuria and ci + ct score, and, separately per each model, DSA (+) (HR
      = 2.446, P = .034), DSA (+)/non-adherent (HR = 3.657, P = .005) and DSA (+)/C1q
      (+) (HR = 4.831, P = .003) status were independent predictors of graft failure.
      CAABMR with concomitant DSA pose a higher risk of graft failure. Adherence should
      be evaluated, and histopathological phenotyping and DSA characterization may add
      critical information.

PMID- 29577963
TI  - Dopamine D1 and D3 receptor polypharmacology as a potential treatment approach
      for substance use disorder.
AB  - In the search for efficacious pharmacotherapies to treat cocaine addiction much
      attention has been given to agents targeting dopamine D1 or D3 receptors because
      of the involvement of these receptors in drug-related behaviors. D1-like and D3
      receptor partial agonists and antagonists have been shown to reduce drug reward,
      reinstatement of drug seeking and conditioned place preference in rodents and non
      human primates. However, translation of these encouraging results to clinical
      settings has been limited due to a number of factors including toxicity, poor
      pharmacokinetic properties and extrapyramidal and sedative side effects. This
      review highlights the role of D1 and D3 receptors in drug reward and seeking, the
      discovery of D1-D3 heteromers and their potential as targets in the treatment of
      addiction.

PMID- 29577964
TI  - Resuscitation registers: How many active registers are there and how many collect
      data on paediatric cardiac arrests?
AB  - BACKGROUND: Cardiac arrest, particularly in children, often has a poor outcome
      and international guidelines highlight significant gaps in the evidence base for
      effective resuscitation. Whilst randomised controlled trials for some
      interventions can be justified, they are not appropriate for many aspects of
      resuscitation. Therefore, guidelines must use other sources of data such as
      epidemiological evidence from cardiac arrest registries, to improve the efficacy
      of resuscitation. The aim of our study was to identify existing national cardiac
      arrest registries and document key information about the registries, including
      whether they contain data on paediatric arrests. METHODS: Key bibliographic
      databases were searched for papers about or using data from cardiac arrest
      registries. Two reviewers independently screened the search results for relevant
      papers. A list of registers named in the papers was compiled and information
      obtained from the papers and the websites of registers where possible. RESULTS:
      Twenty three active national or large regional cardiac arrest registries were
      identified. These included five international collaborations and 10 registries
      that cover a population of at least 10 million people. Twelve registries are
      based in Europe, five in North America, four in Asia and two in Australasia. The
      registries vary in their organisation, but the majority (20) defer to the Utstein
      reporting guidelines for cardiac arrest. Registries covered populations between
      0.4 and 174.5 million and contained between 100 and 605,505 records. Sixteen
      collected data on out-of-hospital arrests only; three in-hospital arrests only;
      and four included both. For ten registers the number of paediatric arrests was
      available and ranged from 56 to 3900. CONCLUSIONS: To our knowledge this report
      contains the most complete list of active national and large regional cardiac
      arrest registries. Register data support current guidelines on effective
      resuscitation however, even the largest registries include relatively small
      numbers, particularly of paediatric events. A less fragmented approach has the
      potential to improve the utility of registration data for the benefit of
      patients.

PMID- 29577965
TI  - Bisphenol A-Induced changes in the enteric nervous system of the porcine
      duodenum.
AB  - Bisphenol A (BPA) is an organic compound from the phenolic group commonly used
      for the production of plastics. The use of BPA in food and drinking water
      containers carries a significant risk to human health since BPA can be washed out
      and enter consumables. BPA entering the human body with food shows a multi
      directional effect and causes disorders in the functioning of many systems and
      organs. There is no current knowledge about the effects of BPA on the enteric
      nervous system. The purpose of the present study was to verify the influence of
      BPA on tolerable daily intake (TDI) dose (0.05 mg/kg body weight/day) and a dose
      ten times higher than TDI (0.5 mg/kg body weight/day) administered for 28 days on
      the porcine duodenum. The neurochemical characterization of the enteric neurons
      to five active neuronal substances was then investigated: substance P (SP),
      vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine
      transporter (VAChT) or cocaine- and amphetamine-regulated transcript peptide
      (CART) with double immunofluorescence method. Both doses of BPA caused visible
      changes in duodenal immunoreactivity to the majority of neuronal factors studied
      and the obtained results show that even TDI dose may affect the living organism.

PMID- 29577966
TI  - Intracellular Delivery of HCV NS3p gene using vectored particles.
AB  - Viral hepatitis caused by the hepatitis C virus (HCV) affects millions of people
      worldwide. The non-structural protein 3 (NS3), one of the most conserved proteins
      in HCV, is the target of many therapeutic studies. The NS3 protease domain (NS3p)
      has a range of cytotoxic T lymphocyte (CTL) epitopes, and synthesizing the
      protein inside the cells is the most appropriate way to present it to the immune
      system. We developed a tool to study this kind of presentation, using two
      vectored particle (VP) systems, one based on the Semliki Forest virus (SFV) and
      the other on HCV pseudoparticles (HCVpp), both carrying the protease domain of
      the NS3 gene. In addition to producing the particles, we developed a method to
      quantify these VPs using qRT-PCR. We produced batches of approximately 2.4 * 104
      SFV-NS3p/MUL and 4.0 * 102 HCVpp-NS3p/MUL. BHK-21 and HuH-7 cells treated with
      the VPs expressed the NS3 protein, thus showing the functionality of this system.

PMID- 29577967
TI  - Comparative analysis of two methods to detect donor-specific anti-HLA antibodies
      after kidney transplant.
AB  - Preformed anti-human leukocyte antigen (HLA) antibodies may be present in the
      blood of kidney transplant candidates. The production of these antibodies may
      occur in the post-transplant period, with the possible development of donor
      specific antibodies (DSA). Luminex-based tests, such as the single antigen (SA)
      assay and the Luminex crossmatch (Xm-DSA) assay are the most commonly used tools
      to detect anti-HLA antibodies, due to their high sensitivity and specificity.
      This cross-sectional study aimed to compare the findings of two methods for the
      detection of DSAs after kidney transplant: SA and Xm-DSA. A total of 122 patients
      who underwent deceased donor kidney transplant at Hospital de Clinicas de Porto
      Alegre were included. The SA assay detected anti-class I HLA DSAs in 17 patients
      (13.9%) and anti-class II HLA DSAs in 22 patients (19.6%), whereas the Xm-DSA
      detected DSAs in 18 patients (14.8%) both against class I and class II antigens.
      There was agreement between the two methods for class I (kappa = 0.66, p = 0.001)
      and class II (kappa = 0.54, p = 0.025) antigens. The incidence of DSAs as
      obtained by the SA assay was 15.57%, and the most prevalent DSAs were those
      against HLA-DR antigens. Patient survival at 3 years was 92%. The two techniques
      assessed in this study provide important information on the presence of DSAs and
      may help in the post-transplant patient monitoring and in immunosuppressive
      strategy.

PMID- 29577968
TI  - Glucocorticoids impair platelet thromboxane biosynthesis in community-acquired
      pneumonia.
AB  - Previous reports suggest that community-acquired pneumonia (CAP) is associated
      with an enhanced risk of myocardial infarction (MI) and that enhanced platelet
      activation may play a role. Aims of this study were to investigate if urinary
      excretion of 11-dehydro-thromboxane (Tx) B2, a reliable marker of platelet
      activation in vivo, was elevated in CAP and whether glucocorticoid administration
      reduced platelet activation. Three-hundred patients hospitalized for CAP were
      recruited and followed-up until discharge. Within the first 2 days from
      admission, urinary 11-dehydro-TxB2 and serum levels of methylprednisolone and
      betamethasone were measured. 11-Dehydro-TxB2 was also measured in a control group
      of 150 outpatients, matched for age, sex, and comorbidities. Finally, in-vitro
      studies were performed to assess if glucocorticoids affected platelet activation,
      at the same range of concentration found in the peripheral circulation of CAP
      patients treated with glucocorticoids. Compared to controls, CAP patients showed
      significantly higher levels of 11-dehydro-TxB2 (110 [69-151] vs. 163 [130-225]
      pg/mg creatinine; p < 0.001). During the in-hospital stay, 31 patients
      experienced MI (10%). A COX regression analysis showed that 11-dehydro-TxB2
      independently predicted MI (p = .005). CAP patients treated with glucocorticoids
      showed significantly lower levels of 11-dehydro-TxB2 compared to untreated ones
      (147 [120-201] vs. 176 [143-250] pg/mg creatinine; p < 0.001). In vitro,
      glucocorticoids-treated platelets showed a dose-dependent decrease of ADP-induced
      platelet aggregation, TxB2 production, cPLA2 phosphorylation and arachidonic acid
      release from the platelet membrane. In conclusion, platelet TxB2 is overproduced
      in CAP patients and may be implicated in MI occurrence. Glucocorticoids reduce
      platelet release of TxB2 in vitro and urinary excretion of 11-dehydro-TxB2 in
      vivo and may be a novel tool to decrease platelet activation in this setting.

PMID- 29577969
TI  - Trypanosoma cruzi infection of human induced pluripotent stem cell-derived
      cardiomyocytes: an in vitro model for drug screening for Chagas disease.
AB  - Chagas disease, caused by Trypanosoma cruzi, is an important global public health
      problem which, despite partial efficacy of benznidazole (Bz) in acute phase,
      urgently needs an effective treatment. Cardiotoxicity is a major safety concern
      for conduction of more accurate preclinical drug screening platforms. Human
      induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) are a reliable
      model to study genetic and infectious cardiac alterations and may improve drug
      development. Herein, we introduce hiPSC-CM as a suitable model to study T. cruzi
      heart infection and to predict the safety and efficacy of anti-T. cruzi drugs.

PMID- 29577970
TI  - Can hi-jacking hypoxia inhibit extracellular vesicles in cancer?
AB  - Increasing evidence indicates that extracellular vesicles (EVs) are key players
      in undesirable cell-cell communication in cancer. However, the release of EVs is
      not unique to cancer cells; normal cells release EVs to perform physiological
      roles. Thus, selective inhibition of EV release from cancer cells is desirable.
      Hypoxia contributes to tumour development and aggressiveness. EV quantities and
      thus undesirable communications are substantially increased in hypoxia. Targeting
      hypoxia could selectively inhibit EV release from tumour cells without disturbing
      physiologically relevant EVs. The unfavourable association between hypoxia and EV
      release is evident in multiple tumour types; therefore, targeting hypoxia could
      have a broad therapeutic benefit.

PMID- 29577971
TI  - Can we accelerate medicinal chemistry by augmenting the chemist with Big Data and
      artificial intelligence?
AB  - AI comes to lead optimization: medicinal chemistry in all disease areas can be
      accelerated by exploiting our pre-competitive knowledge in an unbiased way.

PMID- 29577972
TI  - Reply.

PMID- 29577973
TI  - The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil
      leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic
      kidney disease.
AB  - BACKGROUND: Neutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that
      may be important mediators of chronic inflammation in chronic kidney disease
      (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have the potential to attenuate inflammation through
      production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that
      promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also
      attenuates inflammation by reducing MPO and LTB4. OBJECTIVE: This study evaluated
      the independent and combined effects of n-3 FA and CoQ supplementation on
      neutrophil leukotrienes, the pro-inflammatory eicosanoid 5
      hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD.
      DESIGN: In a double-blind, placebo-controlled intervention of factorial design,
      85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both
      supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and
      calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were
      measured at baseline and after 8 weeks. RESULTS: Seventy four patients completed
      the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB5 (P
      < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1
      (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well
      as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive
      from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not
      significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with
      n-3 FA alone (P = 0.013) but not when given in combination with CoQ. CONCLUSION:
      n-3 FA supplementation in patients with CKD leads to increased neutrophil release
      of LTB5 and several SPM, as well as a reduction in plasma MPO that may have
      important implications for limiting chronic inflammation.

PMID- 29577974
TI  - Repetitions to failure versus not to failure during concurrent training in
      healthy elderly men: A randomized clinical trial.
AB  - This randomized clinical trial compared the neuromuscular adaptations induced by
      concurrent training (CT) performed with repetitions to concentric failure and not
      to failure in elderly men. Fifty-two individuals (66.2 +/- 5.2 years) completed
      the pre- and post-measurements and were divided into three groups: repetitions to
      failure (RFG, n = 17); repetitions not to failure (NFG, n = 20); and repetitions
      not to failure with total volume equalized to RFG (ENFG, n = 15). Participants
      were assessed in isometric knee extension peak torque (PTiso), maximal strength
      (1RM) in the leg press (LP) and knee extension (KE) exercises, quadriceps femoris
      muscle thickness (QF MT), specific tension, rate of torque development (RTD) at
      50, 100 and 250 ms, countermovement jump (CMJ) and squat jump (SJ) performance,
      as well as maximal neuromuscular activity (EMGmax) of the vastus lateralis (VL)
      and rectus femoris (RF) muscles. CT was performed over 12 weeks, twice weekly.
      Along with each specific strength training program, each group also underwent an
      endurance training in the same session. After training, all groups improved
      similarly and significantly in LP and KE 1RM, PTiso, CMJ and SJ performance, RTD
      variables, specific tension, and VL EMGmax, (P < 0.05-0.001). QF MT improved only
      in RFG and ENFG (P < 0.01). These results suggest that repetitions until
      concentric failure does not provide further neuromuscular performance gains and
      muscle hypertrophy, and that even a low number of repetitions relative to the
      maximal possible (i.e., 50%) optimizes neuromuscular performance in elderly men.
      Moreover, training volume appears to be more important for muscle hypertrophy
      than training using maximal repetitions.

PMID- 29577975
TI  - Comparing the effects of a home-based exercise program using a gerontechnology to
      a community-based group exercise program on functional capacities in older adults
      after a minor injury.

PMID- 29577976
TI  - Effects of iron oxide contrast agent in combination with various transfection
      agents during mesenchymal stem cells labelling: An in vitro toxicological
      evaluation.
AB  - The use of iron oxide nanoparticles for different biomedical applications, hold
      immense promise to develop negative tissue contrast in magnetic resonance imaging
      (MRI). Previously, we have optimized the labelling of mesenchymal stem cells
      (MSCs) with iron oxide nanoparticles complexed to different transfection agents
      like poly-l-lysine (IO-PLL) and protamine sulfate (Fe-Pro) on the basis of
      relaxation behaviour and its biological expressions. However, there is a distinct
      need to investigate the biocompatibility and biosafety concerns coupled with its
      cytotoxicity and genotoxicity. This study was prepared to evaluate the viability
      of cells, generation of ROS, changes in actin cytoskeleton, investigation of cell
      death, level of GSH and TAC, activities of SOD and GPx, and stability of DNA in
      MSCs after labelling. Results demonstrated a marginal alteration in toxicological
      parameters like ROS generation, cell length, actin cytoskeleton, total apoptosis
      and DNA damage was detected after stem cell labelling. Insignificant depletion of
      GSH and SOD level, and increase in GPx and TAC level in MSCs were measured after
      labelling with IO-PLL and Fe-Pro complexes, which later on recovered and
      normalized to its baseline. This MSCs labelling could provide a reference
      guideline for toxicological analysis and relaxometry based in vivo MRI detection.

PMID- 29577977
TI  - Transcriptome profiling and cataloging differential gene expression in floral
      buds of fertile and sterile lines of cotton (Gossypium hirsutum L.).
AB  - Cytoplasmic Male Sterility is maternally inherited trait in plants, characterized
      by failure to produce functional pollen during anther development. Anther
      development is modulated through the interaction of nuclear and mitochondrial
      genes. In the present study, differential gene expression of floral buds at the
      sporogenous stage (SS) and microsporocyte stage (MS) between CGMS and its fertile
      maintainer line of cotton plants was studied. A total of 320 significantly
      differentially expressed genes, including 20 down-regulated and 37 up-regulated
      in CGMS comparing with its maintainer line at the SS stage, as well as and 89
      down-regulated and 4 up-regulated in CGMS compared to the fertile line at MS
      stage. Comparing the two stages in the same line, there were 6 down-regulated
      differentially expressed genes only induced in CGMS and 9 up-regulated
      differentially expressed gene only induced in its maintainer. GO analysis
      revealed essential genes responsible for pollen development, and cytoskeleton
      category show differential expression between the fertile and CGMS lines.
      Validation studies by qRT-PCR shows concordance with RNA-seq result. A set of
      novel SSRs identified in this study can be used in evaluating genetic
      relationships among cultivars, QTL mapping, and marker-assisted breeding. We
      reported aberrant expression of genes related to pollen exine formation, and
      synthesis of pectin lyase, myosine heavy chain, tubulin, actin-beta, heat shock
      protein and myeloblastosis (MYB) protein as targets for CMS in cotton. The
      results of this study contribute to basic information for future screening of
      genes and identification of molecular portraits responsible for CMS as well as to
      elucidate molecular mechanisms that lead to CMS in cotton.

PMID- 29577978
TI  - Thrombin promotes PAI-1 expression and migration in keratinocytes via ERK
      dependent Smad linker region phosphorylation.
AB  - Keratinocyte proliferation and migration is essential during re-epithelialisation
      for the restoration of the epithelial barrier during skin wound healing. Numerous
      growth factors are involved in the stimulation of keratinocyte proliferation and
      migration. The signalling pathways that drive these processes during wound
      healing are not well defined. This study investigated thrombin-mediated
      signalling in keratinocytes. The thrombin receptor, protease-activated receptor 1
      (PAR-1) is a seven transmembrane G-protein coupled receptor that is known to
      transactivate the epidermal growth factor receptor (EGFR). Immortalized human
      keratinocytes (HaCaT cells) were treated with thrombin and selective inhibitors
      to EGFR and MAP kinases. Whole cell lysates were separated on SDS-PAGE and
      analysed by Western blot using antibodies against transcription factor Smad2.
      Quantitative real-time polymerase chain reaction was used to measure the mRNA
      expression of PAI-1 while scratch wound assays were used to measure keratinocyte
      migration. Western blot data showed that thrombin mediates PAR-1 transactivation
      of EGFR and the downstream phosphorylation of the transcription factor Smad2
      linker (Smad2L) region. ERK1/2 inhibition by UO126 caused a decrease in Smad2L
      phosphorylation while the p38 inhibitor SB202190 and JNK inhibitor SP600125 did
      not. Smad2L Ser250 was specifically phosphorylated by this thrombin mediated
      pathway while Ser245 and Ser255 were not. Thrombin increased PAI-1 mRNA
      expression and keratinocyte migration and this was reduced when either EGFR or
      ERK1/2 were blocked. Taken together these results show that thrombin mediated
      mRNA expression of PAI-1 in keratinocytes and migration occurs via EGFR
      transactivation and involves signalling intermediates ERK1/2 and Smad2 and may be
      a key pathway in skin wound healing.

PMID- 29577979
TI  - Recent advances in our understanding of the environment's role in allergy.

PMID- 29577980
TI  - Safety of a 2-day ultrarush immunotherapy in vespid allergic patients: Focus on
      elevated serum tryptase.

PMID- 29577982
TI  - Human single-stranded DNA binding protein 1 (hSSB1, OBFC2B), a critical component
      of the DNA damage response.
AB  - Our genomic DNA is found predominantly in a double-stranded helical conformation.
      However, there are a number of cellular transactions and DNA damage events that
      result in the exposure of single stranded regions of DNA. DNA transactions
      require these regions of single stranded DNA, but they are only transient in
      nature as they are particularly susceptible to further damage through chemical
      and enzymatic degradation, metabolic activation, and formation of secondary
      structures. To protect these exposed regions of single stranded DNA, all living
      organisms have members of the Single Stranded DNA Binding (SSB) protein family,
      which are characterised by a conserved oligonucleotide/oligosaccharide-binding
      (OB) domain. In humans, three such proteins members have been identified; namely
      the Replication Protein A (RPA) complex, hSSB1 and hSSB2. While RPA is extremely
      well characterised, the roles of hSSB1 and hSSB2 have only emerged recently. In
      this review, we discuss the critical roles that hSSB1 plays in the maintenance of
      genomic stability.

PMID- 29577981
TI  - Perfluorooctane sulfonate mediates secretion of IL-1beta through PI3K/AKT NF-kB
      pathway in astrocytes.
AB  - Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative compound
      that has been widely used in various fields of life and industrial productions,
      because of its special chemical and physical properties. Numerous studies have
      indicated significant neurotoxic effect of PFOS, especially on neurons and
      microglia. However, the influence of PFOS on astrocyte physiology remains
      unclear. In this study, we showed that PFOS triggered reactive astrocytosis in
      time- and dose-dependent manners. The low-doses of PFOS increased the cell number
      and the expression of glial fibrillary acidic protein (GFAP), a well-known
      hallmark of reactive astrocytes, in C6 astrocyte cells. ELISA and RT-PCR analysis
      showed that PFOS promoted the expression and secretion of Interleukin-1 beta (IL
      1beta) in dose- and time-dependent manners. Furthermore, PFOS exposure could
      induce the phosphorylation and degradation of IkappaBalpha, and the translocation
      of NF-kappaB p65 from the cytoplasm to the nucleus in C6 glioma cell line. Thus,
      the NF-kB signaling pathway can be activated after PFOS exposure. In addition,
      pretreatment with AKT inhibitor LY294002 could obviously attenuate PFOS-induced
      NF-kappaB activation and IL-1beta secretion. Taken together, these results
      indicated that PFOS could facilitate reactive astrocytosis and the secretion of
      pro-inflammatory cytokines through AKT-dependent NF-kappaB signaling pathway.

PMID- 29577983
TI  - Age-related NMDA signaling alterations in SOD2 deficient mice.
AB  - Oxidative stress affects the survival and function of neurons. Hence, they have a
      complex and highly regulated machinery to handle oxidative changes. The
      dysregulation of this antioxidant machinery is associated with a wide range of
      neurodegenerative conditions. Therefore, we evaluated signaling alterations,
      synaptic properties and behavioral performance in 2 and 6-month-old heterozygous
      manganese superoxide dismutase knockout mice (SOD2+/- mice). We found that their
      low antioxidant capacity generated direct oxidative damage in proteins, lipids,
      and DNA. However, only 6-month-old heterozygous knockout mice presented
      behavioral impairments. On the other hand, synaptic plasticity, synaptic strength
      and NMDA receptor (NMDAR) dependent postsynaptic potentials were decreased in an
      age-dependent manner. We also analyzed the phosphorylation state of the NMDAR
      subunit GluN2B. We found that while the levels of GluN2B phosphorylated on
      tyrosine 1472 (synaptic form) remain unchanged, we detected increased levels of
      GluN2B phosphorylated on tyrosine 1336 (extrasynaptic form), establishing
      alterations in the synaptic/extrasynaptic ratio of GluN2B. Additionally, we found
      increased levels of two phosphatases associated with dephosphorylation of p-1472:
      striatal-enriched protein tyrosine phosphatase (STEP) and phosphatase and tensin
      homolog deleted on chromosome Ten (PTEN). Moreover, we found decreased levels of
      p-CREB, a master transcription factor activated by synaptic stimulation. In
      summary, we describe mechanisms by which glutamatergic synapses are altered under
      oxidative stress conditions. Our results uncovered new putative therapeutic
      targets for conditions where NMDAR downstream signaling is altered. This work
      also contributes to our understanding of processes such as synapse formation,
      learning, and memory in neuropathological conditions.

PMID- 29577984
TI  - Cystatin C promotes tau protein phosphorylation and causes microtubule
      instability by inhibiting intracellular turnover of GSK3beta in neurons.
AB  - In Alzheimer's disease (AD) tau protein hyperphosphorylation causes
      neurofibrillary tangle formation, microtubule instability and neurodegeneration.
      Determining the mechanism of tau hyperphosphorylation will provide a better
      understanding of AD pathology. Cystatin C (CysC) is a risk factor for late-onset
      AD and its level is upregulated in the brains of AD patients. The role of CysC is
      AD pathogenesis is not known. In this study, we found that CysC level is
      upregulated in 3xTg-AD mouse brain. We demonstrate that CysC does not affect
      cellular Abeta production. However, when overexpressed in neuron (NGF
      differentiated PC12 cells), CysC inhibits turnover of GSK3beta, promotes GSK3beta
      catalyzed tau phosphorylation at Ser396/404 and causes microtubule instability.
      Our data provide a novel insight into the role of CysC in AD pathogenesis.

PMID- 29577986
TI  - Prurigo Pigmentosa: An Itchy, Urticarial Eruption Confused for Food Allergy.

PMID- 29577985
TI  - RND transporters in the living world.
AB  - Transporters of the RND superfamily are well-known as the major drug efflux pumps
      of Gram-negative bacteria. However, they are widespread in organisms ranging from
      Archaea to Eukaryotes, and perform diverse functions. This review gives a brief
      overview of these diverse members of the superfamily with emphasis on their
      structure and functions.

PMID- 29577987
TI  - Generalized pruritus relieved by NSAIDs in the setting of mast cell activation
      syndrome.

PMID- 29577988
TI  - Genetic polymorphism of Baylisascaris procyonis in host infrapopulations and
      component populations in the Central USA.
AB  - Baylisascaris procyonis is a nematode of significant concern to public and
      domestic animal health as well as wildlife management. The population genetics of
      B. procyonis is poorly understood. To gain insights into patterns of genetic
      diversity within (infrapopulation level) and among (component population level)
      raccoon (Procyon lotor) hosts, and specifically to assess the relative importance
      of indirect and direct transmission of the parasite for explaining observed
      population structure, we collected 69 B. procyonis from 17 wild raccoons
      inhabiting five counties in Missouri and Arkansas, USA. Informative regions of
      mitochondrial (CO1, CO2) and nuclear (28S, ITS2) genes were amplified and the
      distribution and genetic variability of these genes were assessed within and
      across raccoons. Concatenation of the CO1 and CO2 mtDNA sequences resulted in 5
      unique haplotypes, with haplotype diversity 0.456 +/- 0.068. The most common
      haplotype occurred in 94% of raccoons and 72.5% of B. procyonis. Sequences for
      28S rDNA revealed four unique nuclear genotypes, the most common found in 100% of
      raccoons and 82.6% of B. procyonis. ITS2 genotypes were assessed using fragment
      analysis, and there was a 1:1 correspondence between 28S and ITS-2 genotypes.
      Infrapopulation variation in haplotypes and genotypes was high and virtually all
      hosts infected with multiple sequenced nematodes also harbored multiple
      haplotypes and genotypes. There was a positive relationship between the size of
      the analyzed infrapopulation (i.e., the number of nematodes analyzed) and the
      number of haplotypes identified in an individual. Collectively this work
      emphasizes the importance of indirect transmission in the lifecycle to this
      parasite.

PMID- 29577989
TI  - Maintaining Academic Integrity and Preventing Scientific Misconduct in Clinical
      Research.

PMID- 29577990
TI  - Whole genome sequencing in the investigation of recurrent invasive Group A
      streptococcus outbreaks in a maternity unit.
AB  - BACKGROUND: The clinical manifestations of Group A streptococcus (GAS) -
      (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonisation to
      devastating invasive disease. Maternity related clusters of invasive Group A
      streptococcus (iGAS) infection are complex to investigate and control, especially
      if recurrent. AIM: We report on the investigation into three episodes of emm 75
      GAS/iGAS infection in maternity patients at one hospital site over a 4 year
      period, two with monophyletic ancestry. METHODS: The episodes are described,
      together with whole genome sequence isolate analyses. Single nucleotide
      polymorphism differences were compared with contemporaneous emm 75 genomes.
      FINDINGS: Seven mothers had GAS/iGAS in over a 4 year period, emm 75, S.pyogenes
      and one had iGAS (in year 4) emm 3, S.pyogenes (subsequently discounted as
      linked). Three (clinical/screening samples) of the seven babies of emm 75
      positive mothers and 3 screened healthcare workers were positive for GAS emm 75.
      Whole genome sequence similarity suggested a shared ancestral lineage and
      suggested a common source transmission but directionality of transmission cannot
      be inferred. However the findings indicate that persistence of a particular clone
      in a given setting may be long-term. CONCLUSIONS: Occupational health procedures
      were enhanced, staff were screened and antibiotic therapy provided to GAS
      positive staff and patients. The definitive source of infection could not be
      identified, although staff/patient transmission is the most likely route. The
      pattern of clonal GAS transmission over 4 years suggests long-term persistence of
      GAS may have occurred.

PMID- 29577991
TI  - Effect of an exfoliating skincare regimen on the numbers of epithelial squames on
      the skin of operating theatre staff, studied by surface microscopy.
AB  - BACKGROUND: The shedding of epithelial squames (skin scales) by staff in
      operating theatre air is an important source of deep infection following joint
      replacement surgery. This is a serious complication, resulting in significant
      morbidity for the patient and substantial cost implications for healthcare
      systems. Much effort has been put into providing clean air in operating theatres,
      yet little attention has been given to reducing the shedding of surface skin
      scales at source. AIM: To develop a novel method for calculating surface skin
      scale density using surface microscopy, and to use it to evaluate the effect of a
      skincare regimen on operating theatre staff. METHODS: Surface microscopy with Z
      stacked imaging was used to visualize the effect of a skincare regimen involving
      three stages: washing with soap; exfoliation; and application of emollient. A USB
      microscope was then used in a field study to take images of the skin of operating
      theatre staff who applied the regimen to one lower limb the night before testing.
      The other limb was used as a control. Two blinded assessors analysed scale
      density. RESULTS: Z-stack images from the surface microscope enabled observations
      of the skincare regimen. The USB microscope also provided adequate images that
      enabled assessment of skin scale density. In the operating theatre staff, a 72.1%
      reduction in visible skin scales was observed following application of the
      skincare regimen. CONCLUSIONS: Further work is required to demonstrate how this
      effect correlates with dispersion of skin particles in a cleanroom, and
      subsequently in live operating theatre studies.

PMID- 29577992
TI  - Panton-Valentine-producing Staphylococcus aureus: what happens to patients after
      skin decolonization in the community?

PMID- 29577993
TI  - Routine screening for colonization by Gram-negative bacteria in neonates at
      intensive care units for the prediction of sepsis: systematic review and meta
      analysis.
AB  - BACKGROUND: At neonatal intensive care units, sepsis due to Gram-negative
      bacteria is an important cause of morbidity and mortality. The benefits of
      routine microbiological screening of neonatal body surface to predict and prevent
      sepsis are controversial. AIM: To evaluate the prognostic value of neonatal body
      surface screening for colonization with Gram-negative bacteria for the prediction
      of late-onset sepsis. METHODS: A systematic review was performed, including
      studies of any design that reported data to calculate prognostic accuracy of
      surface screening for the prediction of late-onset sepsis. Risk of bias was
      assessed and a meta-analysis performed. Evidence quality was appraised using the
      GRADE (Grading of Recommendations Assessment, Development and Evaluation)
      methodology. FINDINGS: Eight studies (all cohort design) were identified as
      eligible. Studies were performed in six countries in Europe, Asia, and North
      America and comprised a total of 4829 participants. All studies were at high risk
      of bias. Pooled sensitivity of body surface screening to predict late-onset
      sepsis was 41% (95% confidence interval: 17-70), whereas pooled specificity was
      56% (34-76) (hierarchical summary receiver operating characteristics (HSROC)
      model). Subgroup analyses showed higher pooled estimates for specificity but not
      sensitivity when screening focused on Escherichia coli or Klebsiella pneumoniae.
      GRADE evidence quality was very low. CONCLUSION: Limited evidence of very low
      quality exists regarding the prognostic value of neonatal screening for late
      onset sepsis. Carefully planned and conducted prospective studies, including
      randomized trials, are needed to clarify the potential value of this measure for
      the prediction and prevention of late-onset sepsis.

PMID- 29577994
TI  - Acinetobacter pittii isolated more frequently than Acinetobacter baumannii in
      blood cultures: the experience of a French hospital.
AB  - This study assessed the characteristics of hospital-acquired Acinetobacter
      calcoaceticus-Acinetobacter baumannii complex bloodstream infections (BSI). From
      2010 to 2017, A. calcoaceticus-A. baumannii complex BSI were investigated. Of 73
      cases, 54.8% were associated with Acinetobacter pittii, 39.7% with Acinetobacter
      baumannii and 5.5% with Acinetobacter nosocomialis. Multi-drug-resistant isolates
      were significantly higher in A. baumannii BSI. Thirty-day mortality was no
      different between A. baumannii or non-baumannii A. calcoaceticus-A. baumannii
      complex BSI. In contrast with other studies, this study found that most hospital
      acquired A. calcoaceticus-A. baumannii complex BSI were associated with non
      baumannii A. calcoaceticus-A. baumannii complex species. This study found that
      these species were important hospital-acquired pathogens, and emphasizes the
      importance of A. calcoaceticus-A. baumannii complex species identification.

PMID- 29577995
TI  - Microbiological risks of reusing dummies for infants in hospital.

PMID- 29577996
TI  - miR-221-3p Inhibits Schwann Cell Myelination.
AB  - Following peripheral nerve injury, Schwann Cells (SCs) undergo dedifferentiation,
      proliferation, migration, and remyelination. Recent works demonstrated the
      importance of the short non-coding RNA (miRNAs) in SC dedifferentiation and
      remyelination after nerve injury. Previously, we found some miRNAs like miR-9,
      miR-221, miR-222 and miR-182 could regulate the proliferation and migration of
      SCs. Therefore, it is imperative to ask whether these miRNAs could regulate the
      myelination of SCs. Here we demonstrated that miR-221-3p could inhibit the
      myelination of SCs when co-cultured with dorsal root ganglion cells in vitro. In
      addition, NGF1-A binding protein 1 (Nab1) which was essential for SCs myelination
      could be downregulated by miR-221-3p. Suppressing the expression of Nab1 could
      reverse the promotion of miR-221-3p antagomir on SC myelination. The effects of
      miR-221-3p on SC myelination might be used to improve peripheral nerve
      regeneration, thus offering a new approach to peripheral nerve repair.

PMID- 29577997
TI  - Memory for Random Time Patterns in Audition, Touch, and Vision.
AB  - Perception deals with temporal sequences of events, like series of phonemes for
      audition, dynamic changes in pressure for touch textures, or moving objects for
      vision. Memory processes are thus needed to make sense of the temporal patterning
      of sensory information. Recently, we have shown that auditory temporal patterns
      could be learned rapidly and incidentally with repeated exposure [Kang et al.,
      2017]. Here, we tested whether rapid incidental learning of temporal patterns was
      specific to audition, or if it was a more general property of sensory systems. We
      used a same behavioral task in three modalities: audition, touch, and vision, for
      stimuli having identical temporal statistics. Participants were presented with
      sequences of acoustic pulses for audition, motion pulses to the fingertips for
      touch, or light pulses for vision. Pulses were randomly and irregularly spaced,
      with all inter-pulse intervals in the sub-second range and all constrained to be
      longer than the temporal acuity in any modality. This led to pulse sequences with
      an average inter-pulse interval of 166 ms, a minimum inter-pulse interval of 60
      ms, and a total duration of 1.2 s. Results showed that, if a random temporal
      pattern re-occurred at random times during an experimental block, it was rapidly
      learned, whatever the sensory modality. Moreover, patterns first learned in the
      auditory modality displayed transfer of learning to either touch or vision. This
      suggests that sensory systems may be exquisitely tuned to incidentally learn re
      occurring temporal patterns, with possible cross-talk between the senses.

PMID- 29577998
TI  - Dual-task Interference Disrupts Parkinson's Gait Across Multiple Cognitive
      Domains.
AB  - Gait dysfunction, a hallmark of Parkinson's disease, contributes to a relatively
      high incidence of falling. Gait function is further diminished during the
      performance of a motor-cognitive task (i.e., dual-task). It is unclear if
      Parkinson's disease-related dual-task deficits are related to a specific area of
      cognitive function or are the result of a more global decline in executive
      function. The aim of this project was to systematically evaluate gait performance
      to determine if gait dysfunction is restricted to certain types of executive
      function or a global phenomenon in individuals with Parkinson's disease. Twenty
      three individuals with mild-moderate Parkinson's disease completed a series of
      dual-task conditions in which gait was paired with cognitive tasks requiring:
      working memory (0, 1, and 2-back), attention and problem solving (serial-7
      subtraction), verbal memory (digit recall), semantic memory (Controlled Oral Word
      Association) and information processing speed (visual Stroop test). The results
      demonstrate that individuals with mild-moderate Parkinson's disease have a
      generalized worsening of spatial-temporal gait parameters regardless of the
      specific cognitive demand being performed concurrently. Overall, gait velocity
      decreased (p < 0.01) and stride and stance time both increased (p < 0.01) across
      all cognitive conditions. The attention and problem solving task resulted in the
      greatest number of gait parameter decrements. Results indicated that performance
      on cognitive tasks remained unchanged from single-task to dual-task conditions.
      Diminished gait performance under dual-task conditions across different cognitive
      function domains suggests a global Parkinson's disease-related deficit in
      information processing and regulation of gait.

PMID- 29578000
TI  - Monkey extensor digitorum communis motoneuron pool: Proximal dendritic trees and
      small motoneurons.
AB  - Transverse sections of the monkey cervical spinal cord from a previous study
      (Jenny and Inukai, 1983) were reanalyzed using Neurolucida to create a three
      dimensional display of extensor digitorum communis (EDC) motoneurons and proximal
      dendrites that had been labeled with horse radish peroxidase (HRP). The EDC
      motoneuron pool was located primarily in the C8 and T1 segments of the spinal
      cord. Small motoneurons (cell body areas less than 500 MUm2 and presumed to be
      gamma motoneurons) comprised about ten percent of the motoneurons and were
      located throughout the length of the motoneuron pool. Most small motoneurons were
      oblong in shape and had one or two major dendrites originating from the cell body
      in the transverse plane of section. The majority of the HRP labeled dendritic
      trees were directed either superiorly, dorsal-medially to the mid zone area
      between the base of the dorsal horn and the upper portion of the ventral horn, or
      medially to the ventromedial gray matter. The longer HRP labeled dendrites
      usually continued in the same radial direction as when originating from the cell
      body. As such we considered the radial direction of the longer proximal HRP
      labeled dendrites to be a reasonable estimate of the radial direction of the more
      distal dendritic tree. Our data suggest that the motoneuron dendritic tree as
      seen in transverse section has direction-oriented dendrites that extend toward
      functional terminal regions.

PMID- 29577999
TI  - Acute stress alters the rates of degradation of cardiac muscle proteins.
AB  - : Stressful experiences can have detrimental effects on many aspects of health
      and wellbeing. The zebrafish (Danio rerio) is a widely used model for stress
      research and a stress phenotype can be induced by manipulating the environmental
      conditions and social interactions. In this study we have combined a zebrafish
      stress model with the measurement of degradation rates of soluble cardiac muscle
      proteins. The results showed that the greater the stress response in the
      zebrafish the lower the level of overall protein degradation. On comparing the
      rates of degradation for individual proteins it was found that four main pathways
      were altered in response to stress conditions with decreased degradation for
      proteins involved in glucose metabolism, gluconeogenesis, the ubiquitin
      proteasome system (UPS) and peroxisomal proliferator-activated receptor (PPAR)
      signalling pathways. Taken together, these data indicate that under stress
      conditions zebrafish preserve cardiac muscle proteins required for the 'fight or
      flight' response together with proteins that play a role in stress mitigation.
      SIGNIFICANCE: This study is the first to investigate the impact of stressful
      experiences on the dynamics of protein turnover in cardiac muscle. Using an
      established zebrafish model of human stress it has been possible to map key
      pathways at the protein level. The results show that the rates of degradation of
      cardiac proteins involved in glucose metabolism, UPS activity, hypoxia and PPAR
      signalling are decreased in stressed zebrafish. These findings indicate that
      proteins involved in the 'fight or flight' response to stress are conserved by
      the heart together with proteins that play a role in stress mitigation. This work
      provides the basis for more detailed investigations aimed at understanding the
      molecular effects of stress, which has implications for human health and disease.

PMID- 29578001
TI  - Long-term administration of Greek Royal Jelly decreases GABA concentration in the
      striatum and hypothalamus of naturally aged Wistar male rats.
AB  - Royal Jelly (RJ) is a unique substance obtained from bees that has been used
      widely in European and Asian traditional medicine for its potential to prevent
      signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic
      and anti-hypercholesterolemic properties. We recently reported an enhancement in
      spatial memory along with changes in monoaminergic transmission in aged rats
      after chronic RJ administration. Here, we aim to further explore the action of RJ
      on central nervous system activity by examining levels of amino acids in selected
      brain structures of aged male Wistar rats following 2-months of Greek RJ
      administration. RJ powder was previously chemically characterized and given
      orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations
      of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid,
      histidine and taurine) in the brain regions examined (prefrontal cortex,
      hippocampus, striatum and hypothalamus) were quantified using HPLC. We also
      examined basic biochemical parameters of renal and hepatic activity, as damage of
      these organs could potentially explain the changes in brain function and
      behavior. Upon biochemical examination, a decrease in the concentration of gamma
      aminobutyric acid was observed in both the striatum and hypothalamus. Liver and
      kidney functions were not changed by chronic RJ-administration. Our results
      provide insight toward understanding the mechanism of action of RJ and its
      effects on neurotransmission in the central nervous system.

PMID- 29578002
TI  - Inhibition of microRNA-34a protects against propofol anesthesia-induced
      neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway.
AB  - AIM: To investigate the protective effect of microRNA-34a (miR-34a) on propofol
      induced neurotoxicity and cognitive dysfunction. METHODS: After SH-SY5Y cells
      were treated with propofol to induce neurotoxicity, microRNA-34a mimics and
      inhibitors were transfected into the cells. The expression of apoptosis-related
      genes and the proteins were measured by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and western blot. Sprague-Dawley (SD) rats
      received intraperitoneal injections of propofol, and were treated with microRNA
      34a mimics and lentivirus-mediated microRNA-34a inhibitors. The Morris water maze
      (MWM) test was used to detect changes in motor function. RESULTS: Propofol
      anesthesia had an adverse effect on cell survival due to the increased expression
      of apoptosis-related genes such as cleaved caspase-3/8 and Bax, which was
      accompanied by reduced expression of ERK1/2, pERK1/2, and phosphorylated NF
      kappaB p65 both in vivo and in vitro. Unexpectedly, microRNA-34a was upregulated
      after propofol treatment, and the inhibitors protected the SH-SY5Y cells from
      propofol-induced apoptosis. The microRNA-34a inhibitor suppressed the apoptosis
      induced effects of propofol. This protection may have been partly diminished by
      PD98059, a MAPK kinase inhibitor. MicroRNA-34a inhibited or reverted the reduced
      expression of ERK1/2 and upregulated the expression of p-CREB significantly and
      specifically. Additionally, the microRNA inhibitors improved the learning and
      memory functions of animals suffering from neurologic impairment due to propofol
      treatment and reduced cell apoptosis in the hippocampus. CONCLUSION: microRNA-34a
      could improve anesthesia-induced cognitive dysfunction by suppressing cell
      apoptosis and recovering the expression of genes associated with the MAPK/ERK
      signaling pathway.

PMID- 29578003
TI  - Abnormal changes in voltage-gated sodium channels subtypes NaV1.1, NaV1.2,
      NaV1.3, NaV1.6 and CaM/CaMKII pathway in low-grade astrocytoma.
AB  - Epileptic seizures are the main clinical manifestation of low-grade astrocytoma.
      Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. Until now,
      the role of VGSCs and the relationships between calmodulin (CaM)/CaM-dependent
      protein kinase II (CaMKII) and VGSCs in low-grade astrocytoma have not been
      demonstrated. In our study, the protein expression of NaV1.3, NaV1.6 and CaM was
      significantly increased in the tumor compared to control tissue, while the level
      of p-CaMKII/CaMKII was significantly decreased in the tumor group as determined
      by Western Blotting and immunohistochemistry. Furthermore, double-labeling
      immunofluorescence results showed that NaV1.3/NaV1.6 and CaM co-localization was
      significantly increased in the tumor group compared to control tissue. This study
      represents the first evidence of the abnormal changes in VGSCs subtypes and
      CaM/CaMKII pathway in human brain low-grade astrocytoma, providing new potential
      targets for molecular therapies of this disease.

PMID- 29578004
TI  - The triple monoamine re-uptake inhibitor DOV 216,303 promotes functional recovery
      after spinal cord contusion injury in mice.
AB  - Serotonin, noradrenaline and dopamine are important neuromodulators for
      locomotion in the spinal cord. Disruption of descending axons after spinal cord
      injury resulted in reduction of excitatory and neuromodulatory inputs to spinal
      neurons for locomotion. Receptor agonists or reuptake inhibitors for these
      neuromodulators have been shown to be beneficial in incomplete spinal cord
      injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for
      its ability to affect motor function recovery after spinal cord injury in mice.
      We impacted C57 mouse spinal cord at the T11 vertebral level and administered
      vehicle or DOV 216,303 at 10 mg/kg, b.i.d via intraperitoneal injections for 7
      days. We monitored motor function with the Basso Mouse Scale for locomotion for 4
      weeks. Spinal cords were harvested and histological examinations were performed
      to assess tissue sparing and lesion severity. Results showed that DOV 216,303
      treated mice recovered significantly better than vehicle treated mice starting at
      14 days post injury until the end of the survival period. Lesion size of the DOV
      216,303 treated mice was also smaller compared to that of vehicle treated mice.
      This study suggests DOV 216,303 as a potential therapeutic after spinal cord
      injury warrants further investigation.

PMID- 29578005
TI  - Antifungal, antioxidant and cytotoxic activities of chitosan nanoparticles and
      its use as an edible coating on vegetables.
AB  - Chitosan is an abundant non-toxic, biodegradable polymer with versatile
      applications. It is a linear amino polysaccharide obtained from crustacean
      shells. The chitosan nanoparticles (ChNP) prepared by ionic gelation of chitosan
      has greater activity owing to its small size. ChNP has been proved to be
      effective in controlling plants diseases. In this work, we have endeavoured to
      study the antifungal and antioxidant activity of ChNP and use of ChNP as a
      vegetable coating material. The activity of ChNP against selected plant pathogens
      Rhizoctonia solani, Fusarium oxysporum, Collectotrichum acutatum, and
      Phytophthora infestans were studied along with a brief account of its mechanism
      of action. The antioxidant activity of ChNP was also analysed. The ability of
      ChNP as a coating material to improve the shelf life of tomato, chilly and
      brinjal was also studied. The cytotoxicity effect of ChNP against L929 fibroblast
      cells was studied. ChNP had good antifungal activity against all selected
      pathogens compared to Amphotericin B. Significant antioxidant activity was
      obtained. The vegetables coated with different concentrations of ChNP (1%, 2%,
      3%, 4% and 5%) showed decreased weight loss compared to uncoated control. ChNP
      was shown to have decreased cytotoxicity thus making it an ideal antifungal,
      antioxidant and coating agent.

PMID- 29578006
TI  - Preparation and development of FeS2 Quantum Dots on SiO2 nanostructures
      immobilized in biopolymers and synthetic polymers as nanoparticles and nanofibers
      catalyst for antibiotic degradation.
AB  - The FeS2 Quantum Dots (QDs) decorated SiO2 nanostructure were prepared by
      hydrothermal synthesis method. Chitosan and polypyrrole as polymers were used for
      the immobilization process. The characteristic structure of prepared samples was
      analyzed using several techniques such as X-ray diffraction, scanning and
      transmittance electron microscopy, photoluminescence and UV-vis spectroscopy. The
      mean crystallite sizes of FeS2 QDs/SiO2 nanocomposites, FeS2 QDs/SiO2-chitosan
      nanocomposites and FeS2 QDs/SiO2-polypyrrole nanohybrids are 56.12, 76.38, and
      83.24nm, respectively. The band gap energy of FeS2 QDs/SiO2 nanocomposites, FeS2
      QDs/SiO2-chitosan nanocomposites and FeS2 QDs/SiO2-polypyrrole nanohybrids were
      found out to be 3.0, 2.8, and 2.7eV, respectively. The photocatalysis properties
      were investigated by degradation of ampicillin under UV light illumination. The
      effect of experimental variables, such as, pH and time, on photo-degradation
      efficiency was studied. The results show that the three prepared samples
      nanopowders under UV light was in pH3 at 60min. As it could be seen that the
      amount of ampicillin degradation was increased with the loading of FeS2 QDs on
      SiO2 and FeS2 QDs/SiO2 on chitosan nanoparticles and polypyrrole nanofiber. The
      antibacterial experiment was investigated under visible light illumination and
      the FeS2 QDs/SiO2-chitosan nanocomposites and FeS2 QDs/SiO2-polypyrrole
      nanohybrids demonstrate good antibacterial compared to FeS2 QDs/SiO2
      nanocomposites.

PMID- 29578007
TI  - Grafted sesbania gum: A novel derivative for sugarcane juice clarification.
AB  - This work describes the significance of graft copolymer induced flocculation
      process in sugarcane juice clarification. The naturally occurring cinnamic acid
      has been successfully incorporated into the structure of sesbania gum through
      microwave assisted technique (hybrid of conventional and microwave based method)
      to develop novel, non-toxic, eco-friendly product with highly extended structure.
      The customized structure of gum derivative has been characterized by a number of
      modern techniques like 13C NMR, FTIR, SEM, XRD, TGA, DSC, elemental and
      viscometric analysis. The separation of suspended colloidal impurities from cane
      juice has been achieved through the application of synthesized gum derivative as
      a flocculant. The clarification performance of the graft copolymer has been
      evaluated in terms of turbidity, absorbance, and degree brix ( degrees bx). The
      flocculant exhibited maximum efficiency at 1.0ppm (optimized dose) without
      altering the nutritional parameters (% sugar content). The clarified juice thus
      obtained may be used as a beverage for direct consumption or for the manufacture
      of white sugar.

PMID- 29578008
TI  - Surface modification of electrospun PVA/chitosan nanofibers by dielectric barrier
      discharge plasma at atmospheric pressure and studies of their mechanical
      properties and biocompatibility.
AB  - In this paper, surface of electrospun PVA/Cs nanofibers is modified using
      dielectric barrier discharge (DBD) plasma and the relationship between the
      observed mechanical properties and biocompatibility of the nanofibers and plasma
      induced surface properties is discussed. Plasma treatment of electrospun PVA/Cs
      nanofibers is carried out with both inert (argon, Ar) and reactive (oxygen, O2)
      gases at atmospheric pressure. Incorporation of oxygen-containing polar
      functional groups on the surface of Ar-plasma treated (PVA/Cs/Ar) and O2-plasma
      treated (PVA/Cs/O2) nanofibers and increase in surface roughness contribute to
      the improvement of surface wettability and the decrease of contact angle with
      water of the nanofibers. Both PVA/Cs/Ar and PVA/Cs/O2 nanofibers show high
      tensile strength (11.6-15.6%) and Young's modulus (33.8-37.3%) as compared to the
      untreated one. Experimental results show that in terms of haemolytic activity the
      PVA/Cs/Ar and PVA/Cs/O2 nanofibers do not cause structural changes of blood cells
      and meet the biocompatibility requirements for blood-contacting polymeric
      materials. MTT cell viability results further reveals improvement in
      biocompatibility of PVA/Cs nanofibers after Ar and O2 plasma treatment. The
      results suggest that DBD plasma treated electrospun PVA/Cs nanofibers have the
      potential to be used as wound dressing and scaffolds for tissue engineering.

PMID- 29578009
TI  - Amino acid-grafted and N-acylated chitosan thiomers: Construction of 3D bio
      scaffolds for potential cartilage repair applications.

PMID- 29578010
TI  - Characterization, optimization and stability studies on Candida rugosa lipase
      supported on nanocellulose reinforced chitosan prepared from oil palm biomass.
AB  - The contribution of chitosan/nanocellulose (CS-NC) to the enzymatic activity of
      Candida rugosa lipase covalently bound on the surface of CS-NC (CRL/CS-NC) was
      investigated. Cellulosic material from oil palm frond leaves (OPFL) were
      bleached, alkaline treated and acid hydrolyzed to obtain the purified NC and used
      as nano-fillers in CS. XRD, Raman spectroscopy and optical fluorescence
      microscopic analyses revealed existence of strong hydrogen bonds between CS and
      the NC nanofillers. The CRLs were successfully conjugated to the surface of the
      CS-NC supports via imine bonds that occurred through a Schiff's based mechanism.
      Process parameters for the immobilization of CRL were assessed for factors
      temperature, concentration of glutaraldehyde and pH, to afford the highest enzyme
      activity to achieve maximum conversion of butyl butyrate within 3h of incubation.
      Conversion as high as 88% was reached under an optimized condition of 25 degrees
      C, 0.3% glutaraldehyde concentration and buffer at pH7. Thermal stability of
      CRL/CS-NCs was 1.5-fold greater than that of free CRL, with biocatalysts
      reusability for up to 8 successive esterification cycles. This research provides
      a promising approach for expanding the use of NC from OPFL for enhancing enzyme
      activity in favour of an alternative eco-friendly means to synthesize butyl
      butyrate.

PMID- 29578011
TI  - Cross-linked enzyme aggregates of alginate lyase: A systematic engineered
      approach to controlled degradation of alginate hydrogel.
AB  - An enzyme aggregate of alginate lyase (EC 4.2.2.3) from flavobactierium was
      prepared using ammonium sulfate. The resultant aggregates upon cross-linking with
      glutaraldehyde produced insoluble and catalytically active cross-linked enzyme
      aggregate (CLEA) enzyme. The catalytic activity and stability of the cross-linked
      enzyme aggregate of alginate lyase (CLEA-AL) was studied in the presence of
      various pH, temperatures and organic solvents. Reusability, storage stability and
      surface morphology of the CLEA-AL were also studied. The native enzyme and CLEA
      AL exhibited maximum enzyme activity at pH of 6.3 and at a temperature of 40
      degrees C. The CLEA-AL has good stability in nonpolar organic solvents and is
      thermally stable up to 50 degrees C over a period of 8h. By encapsulating CLEA-AL
      into alginate hydrogel, we demonstrate that alginate hydrogels can be
      enzymatically degraded in a controlled fashion. The results also showed that
      degradation of alginate hydrogel with CLEA-AL incorporated beads is slower than
      native enzyme and therefore, CLEA-AL can be used for controlled degradation and
      release of various biologics from the degrading gel.

PMID- 29578012
TI  - Structural characterization and immunomodulating activities of a novel
      polysaccharide from Nervilia fordii.
AB  - Nervilia fordii (Hance) Schltr. has been widely used as a medicinal and edible
      herb in Southwest China and Southeast Asia. In this study, NFP-1, a new water
      soluble polysaccharidewith a purity of 97.8%, was purified from water extract of
      Nervilia fordii by DEAE-cellulose and Sephadex G-100 chromatography. NFP-1 has a
      relative molecular weight of 950 kDa determined by high performance gel
      permeation chromatography (HPGPC). Its monosaccharide compositions were analyzed
      by high performance liquid chromatography (HPLC) after pre-column derivatizing
      its hydrolysate with 1-phenyl-3-methyl-5-pyrazolone (PMP). NFP-1 mainly consists
      of galactose, arabinose, rhamnose, and galacturonic acid. Based on FT-IR,
      methylation and GC-MS analysis, and NMR, the structure unit of NFP-1 was
      established as ->4)-alpha-Rhap-(2-> 4)-alpha-GalpA-(1->2)-alpha-Rhap-(1->2)-alpha
      Rhap-(4->1)-beta-Galp-T containing two branch chains of ->2,4)-alpha-Rhap-(1->5)
      alpha-Araf-(1->3)-alpha-Araf-(1->, and ->2,4)-alpha-Rhap-(1->4)-beta-Galp-(1->.
      The immunomodulatory assays revealed the dual-functionalities of NFP-1. NFP-1
      could significantly induce the secretion of nitric oxide (NO), and promote the
      secretions of TNF-alpha, IL-6, and IL-1beta in RAW264.7 macrophages. NFP-1 could
      also significantly inhibit the production of NO, depress the secretions of TNF
      alpha, IL-6 and IL-1beta in RAW264.7 macrophages activated by lipopolysaccharide
      (LPS), and promote the production of IL-10 meanwhile. Our study suggested that
      Nervilia fordii could be an ideal medicinal or functional food due to its dual
      immunomodulatory activities.

PMID- 29578013
TI  - Properties of cellulose/Antarctic krill protein composite fibers prepared in
      different coagulation baths.
AB  - In this paper, cellulose/Antarctic krill protein composite fibers were obtained
      by wet spinning. The raw materials were recyclable cellulose (C) and Antarctic
      krill protein (AKP), while the solvent was an aqueous solution containing 7wt%
      NaOH and 12wt% urea, which is eco-friendly. The fiber was stretched in a
      coagulation bath containing H2SO4 and Na2SO4. The effects of coagulation at
      different bath concentrations on the mechanical performance, crystallinity, and
      morphology of the C/AKP composite fibers were studied systematically. The break
      strength firstly increased and then decreased with an increase in the
      concentration of the bath. At a coagulation bath concentration of H2SO2/Na2SO4
      (12wt%/12wt%), the crystallinity was 15.16%. Scanning electron microscopy (SEM)
      observations revealed the presence of grooves on the fiber surface. The type and
      percentage of hydrogen bonds in the C/AKP composite fibers were analyzed by
      Fourier transform infrared spectroscopy (FT-IR). On the basis of the obtained
      results, we finally optimized the coagulation bath composition and concentration.

PMID- 29578014
TI  - Development of a reusable and sustainable biocatalyst by immobilization of
      soybean peroxidase onto magnetic adsorbent.
AB  - In this work we synthesized an activated carbon/magnetite composite by a simple
      co-precipitation method. The activated carbon (AC) was synthesized from the solid
      waste obtained in the extraction process of the peroxidase enzyme and the
      magnetic composite was used as support for the immobilization of soybean
      peroxidase (SP). After the determination of the optimal immobilization
      parameters, a 100% yield was achieved under the following conditions:
      support:enzyme proportion of 1.0:0.05 g, equilibration time of 7 h, pH 3.0
      (citrate buffer phosphate 0.1 mol L-1) and temperature of 50  degrees C. The
      determination of pH to the point of zero charge was also done to assist in the
      understanding of the immobilization process at different pH values. Several
      characterization techniques were used, such as thermogravimetric analysis,
      elemental analysis composition, X-ray powder diffraction, Fourier transform
      infrared spectroscopy and Scanning electron microscopy. The biocatalyst presented
      excellent operational stability and was reused for 11 consecutive cycles. The
      magnetic properties inserted in the AC contributed to the removal of the
      biocatalyst from the reaction medium without interfering in the adsorptive
      characteristics of the AC. Thus, the activated carbon/magnetite composite can be
      applied to different research fields with high performance.

PMID- 29578015
TI  - Shelf-life of smoked eel fillets treated with chitosan or thyme oil.
AB  - The present study examined the effect of natural antimicrobials: Chitosan, thyme
      oil and their combination, on the shelf-life of smoked eel fillets stored under
      vacuum packaging (VP) at 4 degrees C. Based on sensory odor data smoked eel
      fillets had a shelf-life of 35 (control), 42 (thyme treated and>49 (thyme,
      chitosan-thyme treated) days. The thiobarbituric acid value (TBA) value of the
      control eel sample was significantly higher than the chitosan-thyme-treated eel
      samples. The use of chitosan singly, or in combination with thyme oil reduced
      lipid oxidation (TBA) of the smoked eel samples. A trimethylamine nitrogen (TMA
      N) value of 10mgN/100g, could be suggested as an indication of smoked eel
      spoilage initiation. Control and treated eel reached total volatile basic
      nitrogen (TVB-N) values of 13.1-31.5mgN/100g below the maximum permissible level
      of TVB-N in fish and fishery products. Eel samples reached the value of
      7.0logcfu/g (Total Plate Count, TPC) on days 35 (smoked) and 42 (thyme treated),
      whereas both chitosan and chitosan-thyme treated eel samples never reached this
      limit value. Results of our study show thyme or chitosan (singly, or in
      combination) inhibit the growth of mesophilic bacteria and extend the shelf-life
      of smoked eel.

PMID- 29578016
TI  - Antioxidant and antimicrobial potential of polysaccharides sequentially extracted
      from Polygonatum cyrtonema Hua.
AB  - We examined the antioxidant and antimicrobial attributes of Polygonatum cyrtonema
      Hua polysaccharides (HBSS, CHSS, DASS, CASS). The UV spectra and FT-IR results
      showed the purity and acidic nature of polysaccharides with beta-configurations.
      DASS (78.585% hydroxyl radical scavenging, 92.794% ABTS radical scavenging,
      75.648% DPPH radical scavenging activity, 0.582 reducing power and 98.721% Fe2+
      chelation at 5mg/mL) possessed the best antioxidant potential; while, HBSS
      (21.113% hydroxyl radical scavenging, 14.412% ABTS radical scavenging, 28.005%
      DPPH radical scavenging activity, 0.285 reducing power and 48.969% Fe2+ chelation
      at 5mg/mL) was observed with the lowest antioxidant action. The bacterial
      inhibition effect of four PCHPs on Gram-positive organisms (B. subtilis and S.
      aureus with the maximum inhibitory diameters of 18.9 and 15.8mm, respectively)
      was better than that of Gram-negative bacteria (E. coli and S. typhimurium with
      the maximum inhibitory diameters of 10.9 and 8.4mm, respectively). The bacterial
      sensitivity was observed in the following order: B. subtilis>S. aureus>E. coli>S.
      typhimurium. The trend of antibacterial action of PCHPs was in following order:
      DASS>CHSS>CASS>HBSS. DASS can be considered as natural anti-oxidant as well as
      spoilage inhibitors to enhance the nutritive and functional values of various
      foods.

PMID- 29578017
TI  - Nanostructured lipid carrier-based pH and temperature dual-responsive hydrogel
      composed of carboxymethyl chitosan and poloxamer for drug delivery.
AB  - The aim of this study was to develop a novel nanostructured lipid carrier (NLC)
      based dual-responsive hydrogel for ocular drug delivery of quercetin (QN). NLC
      loaded with quercetin (QN-NLC) was prepared using melt-emulsification combined
      with ultra-sonication technique. A three-factor five-level central composite
      design (CCD) was employed to optimize the formulation of QN-NLC. The optimized QN
      NLC presented a particle size of 75.54nm with narrow size distribution and high
      encapsulation efficiency (97.14%).QN-NLC was characterized by TEM and DSC. In
      addition, a pH and temperature dual-responsive hydrogel composed of carboxymethyl
      chitosan (CMCS) and poloxamer 407(F127) was constructed by a cross-linking
      reaction with a naturally occurring nontoxic crosslinking agent genipin (GP). FT
      IR was employed to demonstrate that F127/CMCS hydrogel was successfully
      synthesized. The results of SEM analysis and swelling experiments indicated that
      F127/CMCS hydrogel was both temperature-responsive and pH-responsive. From the
      results of In vitro release studies, dual temperature and pH responsiveness of
      the hydrogel was demonstrated, and 80.52% of total quercetin was released from
      the QN-NLC based hydrogel (QN-NLC-Gel) within 3days, revealing QN-NLC-Gel
      released drug sustainably. Taken together, the developed NLC-based hydrogel is a
      promising drug delivery system for the ophthalmic application.

PMID- 29578018
TI  - Genotoxicity and osteogenic potential of sulfated polysaccharides from Caulerpa
      prolifera seaweed.
AB  - Marine algae are sources of novel bioactive molecules and present a great
      potential for biotechnological and biomedical applications. Although green algae
      are the least studied type of seaweed, several of their biological activities
      have already been described. Here, we investigated the osteogenic potential of
      Sulfated Polysaccharide (SP)-enriched samples extracted from the green seaweed
      Caulerpa prolifera on human mesenchymal stem cells isolated from Wharton jelly
      (hMSC-WJ). In addition, the potential genotoxicity of these SPs was determined by
      cytokinesis-block micronucleus (CBMN) assay. SP-enriched samples did not show
      significant cytotoxicity towards hMSCs-WJ at a concentration of up to 10MUg/mL,
      and after 72h of exposure. SP enrichment also significantly increased alkaline
      phosphatase (ALP) activity, promoting calcium accumulation in the extracellular
      matrix. Among the SP-enriched samples, the CP0.5 subfraction (at 5MUg/mL)
      presented the most promising results. In this sample, ALP activity was increased
      approximately by 60%, and calcium accumulation was approximately 6-fold above the
      negative control, indicating high osteogenic potential. This subfraction also
      proved to be non-genotoxic, according to the CBMN assay, as it did not induce
      micronuclei. The results of this study highlight, for the first time, the
      potential of these SPs for the development of new therapies for bone
      regeneration.

PMID- 29578019
TI  - Preparation and characterization of chitosan-based antimicrobial active food
      packaging film incorporated with apple peel polyphenols.
AB  - In the present study, apple peel polyphenols (APP) were incorporated into
      chitosan (CS) to develop a novel functional film. Scanning electron microscopy,
      Fourier transform-infrared spectroscopy and thermogravimetric analyses were
      performed to study the structure, potential interaction and thermal stability of
      the prepared films. Physical properties including moisture content, density,
      color, opacity, water solubility, swelling ration and water vapor permeability
      were measured. The results revealed that addition of APP into CS significantly
      improved the physical properties of the film by increasing its thickness,
      density, solubility, opacity and swelling ratio whereas moisture content and
      water vapor permeability were decreased. Tensile strength and elongation at break
      of the CS-APP film with 1% APP was 16.48MPa and 13.33%, respectively,
      significantly lower than those for CS control film. Thermal stability of the
      prepared films was decreased while antioxidant and antimicrobial activities of
      the CS-based APP film were significantly increased. CS-APP film with 0.50% APP
      concentration exhibited good mechanical and antimicrobial properties, indicating
      that it could be developed as bio-composite food packaging material for the food
      industry.

PMID- 29578020
TI  - Molecular docking and in vitro studies of soap nut trypsin inhibitor (SNTI)
      against phospholipase A2 isoforms in therapeutic intervention of inflammatory
      diseases.
AB  - Therapeutic value of allelochemicals in inflammatory disorders and the potential
      drug targets need to be elucidated to alleviate tissue and vascular injury.
      Natural anti-inflammatory agents are known to cause minimal adverse effects.
      Presence of different secondary metabolites (allelochemicals), protease
      inhibitors like soap nut trypsin inhibitor (SNTI) from Sapindus trifoliatus and
      allied compounds from natural sources cannot be blithely ignored as natural
      therapeutics. In the present study, SNTI, a prospective protease inhibitor
      isolated from the seeds of Sapindus trifoliatus were subjected to docking against
      three isoforms of Phospholipase A2 (PLA2) molecules of the inflammatory pathways
      which are localized in the membrane, cytosol and pancreas. Eleven ligand
      molecules were selected from Sapindus trifoliatus and docked against membrane,
      cytosolic and pancreatic PLA2. Cytosolic PLA2 showed a strong inhibition by
      Kampferol, a secondary metabolite from seed endosperm of Sapindus trifoliatus.
      SNTI showed best interaction with membrane PLA2 in both in silico as well as in
      in vitro studies. SNTI showed IC50 value of 29.02 MUM in in vitro assay. Docking
      interaction profiles and in vitro studies validate selected molecules from
      Sapindus trifoliatus as immunomodulators and can mollify inflammatory responses.

PMID- 29578021
TI  - Biocompatible scaffolds based on natural polymers for regenerative medicine.
AB  - The chitosan and gelatine are commonly used biopolymers for the tissue
      engineering applications. In the previous methods for the cryogels synthesis,
      multistep preparation methods using toxic cross-linking agents such as
      glutaraldehyde are reported. Here, we present a two-step preparation method of
      gelatin macroporous cryogels and one-step preparation method of chitosan or
      gelatin cryogels. The physico-chemical properties of obtained scaffolds were
      characterized using FTIR, zeta potential, SEM and laser confocal microscopy. Non
      toxic and biodegradable cross-linking agents such as oxidized dextran and 1,1,3,3
      tetramethoxypropane are utilized. The one-step chitosan cryogels had degradation
      degree ~2 times higher compared to the cryogels prepared with a two-step method
      i.e. reduced by borohydride. Scaffolds cross-linked by glutaraldehyde had about
      40% viability, whereas nine various compositions of cryogels showed significantly
      higher viability (~80%) of fibroblast cells in vitro. The cryogels were obtained
      without using the harmful compounds and therefore can be used straightforward as
      biocompatible and biodegradable scaffolds for the cell culturing purposes and
      other biomedical applications.

PMID- 29578022
TI  - Compositional analysis of sulfated polysaccharides from sea cucumber (Stichopus
      japonicus) released by autolysis reaction.
AB  - Autolysis is not only a major reason for postharvest quality deterioration of sea
      cucumber, but also a promising alternative for exogenous protease to produce
      peptides or polysaccharides. However, little has been known about the effects of
      autolysis on bioactive polysaccharides of sea cucumber. Concerning the quality
      and safety of sea cucumber products involved autolysis reaction, the present
      study focused on the chemical composition of sulfated polysaccharides (SPs)
      released by autolysis reaction. Chemical analysis indicated that after 3-day
      autolysis 63% of sulfated polysaccharides were liberated but with protein chains
      at their reducing ends. Then the composition of SP obtained by autolysis (A-SP)
      was compared with that of total SPs (T-SP) via a series of analysis techniques,
      including FTIR, 1H NMR, HPLC and mass spectroscopy. As indicated by the results,
      fucan to fucosylated chondroitin sulfate ratio was found high in A-SP compared to
      T-SP, fucan with a lower molecular weight was the major fraction in A-SP, and the
      di-sulfated Fuc residue observed in T-SP was absent in A-SP. To conclude, A-SP
      differed greatly from T-SP in the chemical composition, suggesting possible
      changes on their bioactivities.

PMID- 29578023
TI  - Effect of organic additives on physiochemical properties and anti-oxidant release
      from chitosan-gelatin composite films to fatty food simulant.
AB  - Chitosan, gelatin and their blended films prepared and compared in some optical,
      physical and mechanical properties. The release rate of Gallic acid (GA) from the
      film to food fatty simulant studied. The chitosan- gelatin based films showed
      appropriate compatibility and desirable properties in comparison with singular
      gelatin and chitosan film. GA was added using different methods including simple
      addition, with two concentration of tween, with ethanol, with beta-Cyclodextrin
      (beta-CD) in physical mixture and encapsulated form. Incorporation of GA causes
      leads to formation of weak and dark samples. Use of beta-CD with GA decreased
      tensile strength (TS) significantly. Film samples with physical mixture of beta
      CD and GA indicated lower barrier properties against water vapor and release rate
      in comparison with their inclusion complex. Incorporation of tween 20, at low
      concentration leads to higher release rate, elongation at break (EB%) and water
      vapor permeability (WVP). Due to the lowest release rate observed for samples
      with ethanol as well as almost good (desirable) physical and mechanical
      properties, it could be appropriate candidate for fatty food packaging in long
      period. On the other hand, highest rate related to samples contained GA- beta-CD
      inclusion complex, which are suitable to higher anti-oxidant demands and short
      term protection.

PMID- 29578024
TI  - Stimulus-responsive zinc oxide-functionalized macromolecular humic acid
      nanocarrier for enhancement of antibacterial activity of ciprofloxacin
      hydrochloride.
AB  - Macromolecular of naturally occurring humic acid (HA) have garnered interest in
      the chemical, biological and medicine industry owing to their unique behavior,
      i.e., strong adsorptive and non-toxic nature. Here, we investigated the
      functionalization of organic (HA) with inorganic (ZnO) hybrid nanoparticles for
      topical and site-targeted delivery of ciprofloxacin by simple emulsification
      techniques. Ciprofloxacin (CIPRO)-encapsulated hybrid nanocarrier constitute an
      attractive novel drug delivery vehicle for sustained release of antibiotics to
      bacterial infection sites in an extended and controlled manner. The analytical
      characteristics of the designed system were thoroughly investigated by FTIR, XRD,
      SEM/EDAX, and TEM. The drug release of ciprofloxacin over 24h was 87.5%, 98.03%,
      97.44%, and 97.24% for pH2.5, 5.5, 6.8, and 8.0, respectively. The antibacterial
      activities results confirmed that the CIPRO-encapsulated hybrid nanocarrier
      showed excellent growth inhibition against microorganisms. This hybrid
      nanocarrier loaded with antibiotics represents a promising approach for targeted
      and controlled drug delivery to infected sites.

PMID- 29578026
TI  - A subject-transfer framework for obviating inter- and intra-subject variability
      in EEG-based drowsiness detection.
AB  - Inter- and intra-subject variability pose a major challenge to decoding human
      brain activity in brain-computer interfaces (BCIs) based on non-invasive
      electroencephalogram (EEG). Conventionally, a time-consuming and laborious
      training procedure is performed on each new user to collect sufficient
      individualized data, hindering the applications of BCIs on monitoring brain
      states (e.g. drowsiness) in real-world settings. This study proposes applying
      hierarchical clustering to assess the inter- and intra-subject variability within
      a large-scale dataset of EEG collected in a simulated driving task, and validates
      the feasibility of transferring EEG-based drowsiness-detection models across
      subjects. A subject-transfer framework is thus developed for detecting drowsiness
      based on a large-scale model pool from other subjects and a small amount of alert
      baseline calibration data from a new user. The model pool ensures the
      availability of positive model transferring, whereas the alert baseline data
      serve as a selector of decoding models in the pool. Compared with the
      conventional within-subject approach, the proposed framework remarkably reduced
      the required calibration time for a new user by 90% (18.00 min-1.72 +/- 0.36 min)
      without compromising performance (p = 0.0910) when sufficient existing data are
      available. These findings suggest a practical pathway toward plug-and-play
      drowsiness detection and can ignite numerous real-world BCI applications.

PMID- 29578025
TI  - The role of the right superior temporal gyrus in stimulus-centered spatial
      processing.
AB  - Although emerging neuropsychological evidence supports the involvement of
      temporal areas, and in particular the right superior temporal gyrus (STG), in
      allocentric neglect deficits, the role of STG in healthy spatial processing
      remains elusive. While several functional brain imaging studies have demonstrated
      involvement of the STG in tasks involving explicit stimulus-centered judgments,
      prior rTMS studies targeting the right STG did not find the expected neglect-like
      rightward bias in size judgments using the conventional landmark task. The
      objective of the current study was to investigate whether disruption of the right
      STG using inhibitory repetitive transcranial magnetic stimulation (rTMS) could
      impact stimulus-centered, allocentric spatial processing in healthy individuals.
      A lateralized version of the landmark task was developed to accentuate the
      dissociation between viewer-centered and stimulus-centered reference frames. We
      predicted that inhibiting activity in the right STG would decrease accuracy
      because of induced rightward bias centered on the line stimulus irrespective of
      its viewer-centered or egocentric locations. Eleven healthy, right-handed adults
      underwent the lateralized landmark task. After viewing each stimulus,
      participants had to judge whether the line was bisected, or whether the left
      (left-long trials) or the right segment (right-long trials) of the line was
      longer. Participants repeated the task before (pre-rTMS) and after (post-rTMS)
      receiving 20 min of 1 Hz rTMS over the right STG, the right supramarginal gyrus
      (SMG), and the vertex (a control site) during three separate visits. Linear mixed
      models for binomial data were generated with either accuracy or judgment errors
      as dependent variables, to compare 1) performance across trial types (bisection,
      non-bisection), and 2) pre- vs. post-rTMS performance between the vertex and the
      STG and the vertex and the SMG. Line eccentricity (z = 4.31, p < 0.0001) and line
      bisection (z = 5.49, p < 0.0001) were significant predictors of accuracy. In the
      models comparing the effects of rTMS, a significant two-way interaction with STG
      (z = -3.09, p = 0.002) revealed a decrease in accuracy of 9.5% and an increase in
      errors of the right-long type by 10.7% on bisection trials, in both left and
      right viewer-centered locations. No significant changes in leftward errors were
      found. These findings suggested an induced stimulus-centered rightward bias in
      our participants after STG stimulation. Notably, accuracy or errors were not
      influenced by SMG stimulation compared to vertex. In line with our predictions,
      the findings provide compelling evidence for right STG's involvement in healthy
      stimulus-centered spatial processing.

PMID- 29578027
TI  - Distinct and overlapping fusiform activation to faces and food.
AB  - The fusiform cortex is a part of the ventral visual stream and is typically
      associated with face processing. Indeed, a subregion of the fusiform has been
      named the "fusiform face area" or FFA, based on its robust response to faces
      relative to other objects. In a separate literature, appetizing food has also
      been shown to activate bilateral fusiform cortex, yet no study to date has
      directly compared face and food responses within the same paradigm. Here, we use
      functional magnetic resonance imaging (fMRI) to compare face and food responses
      in ventral visual cortex and other regions that are typically associated with
      face processing. We present evidence that a region of the left fusiform cortex
      (typically associated with face processing) actually responds equally to faces
      and food. We go on to describe the similarities and differences in location of
      face- and food-responses in the fusiform, the relationship of fusiform activation
      to body mass index (BMI), and resting state connectivity of face- and food
      selective fusiform. Results are interpreted within a model in which motivational
      relevance or value influence fusiform response.

PMID- 29578028
TI  - Changes in alpha activity reveal that social opinion modulates attention
      allocation during face processing.
AB  - Participants' performance differs when conducting a task in the presence of a
      secondary individual, moreover the opinion the participant has of this individual
      also plays a role. Using EEG, we investigated how previous interactions with, and
      evaluations of, an avatar in virtual reality subsequently influenced attentional
      allocation to the face of that avatar. We focused on changes in the alpha
      activity as an index of attentional allocation. We found that the onset of an
      avatar's face whom the participant had developed a rapport with induced greater
      alpha suppression. This suggests greater attentional resources are allocated to
      the interacted-with avatars. The evaluative ratings of the avatar induced a U
      shaped change in alpha suppression, such that participants paid most attention
      when the avatar was rated as average. These results suggest that attentional
      allocation is an important element of how behaviour is altered in the presence of
      a secondary individual and is modulated by our opinion of that individual.

PMID- 29578029
TI  - UBO Detector - A cluster-based, fully automated pipeline for extracting white
      matter hyperintensities.
AB  - We present 'UBO Detector', a cluster-based, fully automated pipeline for
      extracting and calculating variables for regions of white matter hyperintensities
      (WMH) (available for download at https://cheba.unsw.edu.au/group/neuroimaging
      pipeline). It takes T1-weighted and fluid attenuated inversion recovery (FLAIR)
      scans as input, and SPM12 and FSL functions are utilised for pre-processing. The
      candidate clusters are then generated by FMRIB's Automated Segmentation Tool
      (FAST). A supervised machine learning algorithm, k-nearest neighbor (k-NN), is
      applied to determine whether the candidate clusters are WMH or non-WMH. UBO
      Detector generates both image and text (volumes and the number of WMH clusters)
      outputs for whole brain, periventricular, deep, and lobar WMH, as well as WMH in
      arterial territories. The computation time for each brain is approximately 15
      min. We validated the performance of UBO Detector by showing a) high segmentation
      (similarity index (SI) = 0.848) and volumetric (intraclass correlation
      coefficient (ICC) = 0.985) agreement between the UBO Detector-derived and
      manually traced WMH; b) highly correlated (r2 > 0.9) and a steady increase of WMH
      volumes over time; and c) significant associations of periventricular (t =
      22.591, p < 0.001) and deep (t = 14.523, p < 0.001) WMH volumes generated by UBO
      Detector with Fazekas rating scores. With parallel computing enabled in UBO
      Detector, the processing can take advantage of multi-core CPU's that are commonly
      available on workstations. In conclusion, UBO Detector is a reliable, efficient
      and fully automated WMH segmentation pipeline.

PMID- 29578030
TI  - Practices and pitfalls in inferring neural representations.
AB  - A key challenge for cognitive neuroscience is deciphering the representational
      schemes of the brain. Stimulus-feature-based encoding models are becoming
      increasingly popular for inferring the dimensions of neural representational
      spaces from stimulus-feature spaces. We argue that such inferences are not always
      valid because successful prediction can occur even if the two representational
      spaces use different, but correlated, representational schemes. We support this
      claim with three simulations in which we achieved high prediction accuracy
      despite systematic differences in the geometries and dimensions of the underlying
      representations. Detailed analysis of the encoding models' predictions showed
      systematic deviations from ground-truth, indicating that high prediction accuracy
      is insufficient for making representational inferences. This fallacy applies to
      the prediction of actual neural patterns from stimulus-feature spaces and we urge
      caution in inferring the nature of the neural code from such methods. We discuss
      ways to overcome these inferential limitations, including model comparison,
      absolute model performance, visualization techniques and attentional modulation.

PMID- 29578031
TI  - The UNC/UMN Baby Connectome Project (BCP): An overview of the study design and
      protocol development.
AB  - The human brain undergoes extensive and dynamic growth during the first years of
      life. The UNC/UMN Baby Connectome Project (BCP), one of the Lifespan Connectome
      Projects funded by NIH, is an ongoing study jointly conducted by investigators at
      the University of North Carolina at Chapel Hill and the University of Minnesota.
      The primary objective of the BCP is to characterize brain and behavioral
      development in typically developing infants across the first 5 years of life. The
      ultimate goals are to chart emerging patterns of structural and functional
      connectivity during this period, map brain-behavior associations, and establish a
      foundation from which to further explore trajectories of health and disease. To
      accomplish these goals, we are combining state of the art MRI acquisition and
      analysis techniques, including high-resolution structural MRI (T1-and T2-weighted
      images), diffusion imaging (dMRI), and resting state functional connectivity MRI
      (rfMRI). While the overall design of the BCP largely is built on the protocol
      developed by the Lifespan Human Connectome Project (HCP), given the unique age
      range of the BCP cohort, additional optimization of imaging parameters and
      consideration of an age appropriate battery of behavioral assessments were
      needed. Here we provide the overall study protocol, including approaches for
      subject recruitment, strategies for imaging typically developing children 0-5
      years of age without sedation, imaging protocol and optimization, a description
      of the battery of behavioral assessments, and QA/QC procedures. Combining HCP
      inspired neuroimaging data with well-established behavioral assessments during
      this time period will yield an invaluable resource for the scientific community.

PMID- 29578032
TI  - CaV3.1 isoform of T-type calcium channels supports excitability of rat and mouse
      ventral tegmental area neurons.
AB  - Recent data have implicated voltage-gated calcium channels in the regulation of
      the excitability of neurons within the mesolimbic reward system. While the
      attention of most research has centered on high voltage L-type calcium channel
      activity, the presence and role of the low voltage-gated T-type calcium channel
      (T-channels) has not been well explored. Hence, we investigated T-channel
      properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type
      (WT) rats and mice, CaV3.1 knock-out (KO) mice, and TH-eGFP knock-in (KI) rats in
      acute horizontal brain slices of adolescent animals. In voltage-clamp
      experiments, we first assessed T-channel activity in WT rats with characteristic
      properties of voltage-dependent activation and inactivation, as well as
      characteristic crisscrossing patterns of macroscopic current kinetics. T-current
      kinetics were similar in WT mice and WT rats but T-currents were abolished in
      CaV3.1 KO mice. In ensuing current-clamp experiments, we observed the presence of
      hyperpolarization-induced rebound burst firing in a subset of neurons in WT rats,
      as well as dopaminergic and non-dopaminergic neurons in TH-eGFP KI rats.
      Following the application of a pan-selective T-channel blocker TTA-P2, rebound
      bursting was significantly inhibited in all tested cells. In a behavioral
      assessment, the acute locomotor increase induced by a MK-801 (Dizocilpine)
      injection in WT mice was abolished in CaV3.1 KO mice, suggesting a tangible role
      for 3.1 T-type channels in drug response. We conclude that pharmacological
      targeting of CaV3.1 isoform of T-channels may be a novel approach for the
      treatment of disorders of mesolimbic reward system.

PMID- 29578033
TI  - Propranolol produces short-term facilitation of extinction in a rabbit model of
      post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is a learning-based anxiety disorder with
      significant public health challenges due to difficulties in treating the complex,
      multiple symptomology. We have developed an animal model of PTSD, based on
      Pavlovian eyeblink conditioning in rabbits, that addresses two key features:
      conditioned responses (CRs) to cues associated with an aversive event and a form
      of conditioned hyperarousal referred to as conditioning-specific reflex
      modification (CRM). We have found previously that unpaired extinction is ideal
      for reducing both CRs and CRM simultaneously and shows sensitivity to systemic
      serotonergic and glutamatergic manipulations. The following study aimed to extend
      our work to examine the role of the noradrenergic system, dysregulation of which
      is strongly implicated as part of the neurobiology of PTSD and which may also
      play a role in the balance shift from fear reconsolidation to extinction during
      treatment. The goal of the following two studies was to examine whether the beta
      adrenergic receptor antagonist propranolol combined with either a full or brief
      course of unpaired extinction treatment could enhance extinction of CRs and/or
      CRM. Results showed a within-session facilitation of propranolol on extinction of
      CRs, particularly during the first extinction session, and a short-term
      enhancement of extinction of CRM when extinction treatment was brief. However,
      neither benefit translated to long-term extinction retention for the majority of
      subjects. Findings suggest that propranolol may provide the most therapeutic
      benefit in situations of high arousal early in treatment, which may be more
      important for future patient compliance rather than long-term treatment outcomes.

PMID- 29578034
TI  - The reduction in glutamate release is predictive of cognitive and emotional
      alterations that are corrected by the positive modulator of AMPA receptors S
      47445 in perinatal stressed rats.
AB  - S 47445 is a positive modulator of glutamate AMPA-type receptors, possessing
      neurotrophic and enhancing synaptic plasticity effects as well as pro-cognitive
      and anti-stress properties. Here, the drug was assessed in the perinatal stress
      (PRS) rat model, known to have a high predictive validity with monoaminergic
      antidepressants. The effects of a chronic treatment (i.p.) with S 47445 were
      investigated on risk-taking, motivational and cognitive behavior. S 47445 (1 and
      10 mg/kg) increased the exploration of the elevated-plus maze and light/dark box
      as well as the time spent grooming in the splash test, and improved social memory
      in PRS rats. Also, the effects of S 47445 were examined on the synaptic
      neurotransmission. The reduced depolarization-evoked glutamate release induced by
      PRS was corrected with S 47445 (10 mg/kg). Remarkably, the reduction in glutamate
      release induced by PRS and corrected by S 47445 chronic treatment was correlated
      with all the behavioral changes. S 47445 at 10 mg/kg also normalized the lower
      levels of synaptic vesicle-associated proteins in ventral hippocampus in PRS
      rats. Finally, S 47445 reversed the decrease of mGlu5 receptors, GR and OXTR
      induced by PRS. Collectively, in an animal model of stress-related disorders, S
      47445 corrected the imbalance between excitatory and inhibitory neurotransmission
      by regulating glutamate-evoked release that is predictive of PRS behavioral
      alterations, and also normalized the reduction of trafficking of synaptic
      vesicles induced by PRS. These results support the interest of glutamatergic
      based therapeutic strategies to alleviate stress-related disorders.

PMID- 29578035
TI  - Ras inhibitor S-trans, trans-farnesylthiosalicylic acid enhances spatial memory
      and hippocampal long-term potentiation via up-regulation of NMDA receptor.
AB  - Statins by reducing farnesyl-pyrophosphate or farnesyl transferase inhibitors
      have been demonstrated to enhance spatial memory and long-term potentiation
      (LTP). The objective of this study was to investigate effects of the synthetic
      Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) on spatial
      cognitive function in adult mice, synaptic plasticity in hippocampal CA1 regions,
      and NMDA receptor (NMDAr) activity of pyramidal cells. Here, we show that
      administering FTS (5 mg/kg, i.p.) enhanced spatial cognitive performance, as
      assessed via Morris water maze and Y-maze tests. Treating hippocampal slices with
      FTS (5 MUM) for 2 h enhanced selectively NMDAr-dependent LTP without changing the
      synaptic properties. In comparison with the controls, the FTS-treated slices
      showed increases in the amplitude of NMDA-evoked currents (INMDA) and the
      phosphorylation of NMDAr GluN2A/GluN2B subunits and Src. The Src inhibitor PP2
      blocked the enhancing effects of FTS on the activity and phosphorylation of
      NMDAr. In FTS-treated slices, basal levels of CaMKII, ERK2 and CREB
      phosphorylation did not differ significantly from those of controls; however,
      high-frequency stimulation-induced increases in CaMKII, ERK2 and CREB
      phosphorylation were more significant than in the controls, which were sensitive
      to PP2 and NMDAr antagonist MK801. Furthermore, the phosphorylation of AMPA
      receptor GluR1 during LTP was higher in FTS-treated slices compared with the
      control, which depended on Src and ERK1/2 signaling. The results indicate that
      the Ras inhibition by FTS can enhance NMDAr-dependent LTP by increasing Src
      activity to promote NMDAr GluN2A/GluN2B phosphorylation, which then leads to
      spatial memory potentiation.

PMID- 29578036
TI  - mGlu4 allosteric modulation for treating Parkinson's disease.
AB  - 2017 is the 200th anniversary of the first published description of Parkinson's
      disease (PD). Fifty years ago, the clinical benefit of levodopa was first
      documented, representing the most important advance in the treatment of PD so
      far. Among the novel targets identified in the last decade, positive allosteric
      modulators (PAM) of mGlu4 receptors show great promise, with the potential to
      change the paradigm of the PD treatment approach. mGlu4 PAMs have shown
      consistent efficacy in various preclinical models of PD, and entered clinical
      trials for the first time in 2017. This review synthesizes the rationale for
      mGlu4 PAM development for PD and progress to date, reporting the key achievements
      from preclinical studies to the first-in-class compound assessment in man.

PMID- 29578038
TI  - An ensemble learning system for a 4-way classification of Alzheimer's disease and
      mild cognitive impairment.
AB  - Discriminating Alzheimer's disease (AD) from its prodromal form, mild cognitive
      impairment (MCI), is a significant clinical problem that may facilitate early
      diagnosis and intervention, in which a more challenging issue is to classify MCI
      subtypes, i.e., those who eventually convert to AD (cMCI) versus those who do not
      (MCI). To solve this difficult 4-way classification problem (AD, MCI, cMCI and
      healthy controls), a competition was hosted by Kaggle to invite the scientific
      community to apply their machine learning approaches on pre-processed sets of T1
      weighted magnetic resonance images (MRI) data and the demographic information
      from the international Alzheimer's disease neuroimaging initiative (ADNI)
      database. This paper summarizes our competition results. We first proposed a
      hierarchical process by turning the 4-way classification into five binary
      classification problems. A new feature selection technology based on relative
      importance was also proposed, aiming to identify a more informative and concise
      subset from 426 sMRI morphometric and 3 demographic features, to ensure each
      binary classifier to achieve its highest accuracy. As a result, about 2% of the
      original features were selected to build a new feature space, which can achieve
      the final four-way classification with a 54.38% accuracy on testing data through
      hierarchical grouping, higher than several alternative methods in comparison.
      More importantly, the selected discriminative features such as hippocampal
      volume, parahippocampal surface area, and medial orbitofrontal thickness, etc. as
      well as the MMSE score, are reasonable and consistent with those reported in
      AD/MCI deficits. In summary, the proposed method provides a new framework for
      multi-way classification using hierarchical grouping and precise feature
      selection.

PMID- 29578037
TI  - Cocaine evokes a profile of oxidative stress and impacts innate antiviral
      response pathways in astrocytes.
AB  - HIV-1 and Zika virus (ZIKV) represent RNA viruses with neurotropic
      characteristics. Infected individuals suffer neurocognitive disorders aggravated
      by environmental toxins, including drugs of abuse such as cocaine, exacerbating
      HIV-associated neurocognitive disorders through a combination of astrogliosis,
      oxidative stress and innate immune signaling; however, little is known about how
      cocaine impacts the progression of ZIKV neural perturbations. Impaired innate
      immune signaling is characterized by weakened antiviral activation of interferon
      signaling and alterations in inflammatory signaling, factors contributing to
      cognitive sequela associated with cocaine in HIV-1/ZIKV infection. We employed
      cellular/molecular biology techniques to test if cocaine suppresses the efficacy
      of astrocytes to initiate a Type 1 interferon response to HIV-1/ZIKV, in vitro.
      We found cocaine activated antiviral signaling pathways and type I interferon in
      the absence of inflammation. Cocaine pre-exposure suppressed antiviral responses
      to HIV-1/ZIKV, triggering antiviral signaling and phosphorylation of interferon
      regulatory transcription factor 3 to stimulate type I interferon gene
      transcription. Our data indicate that oxidative stress is a major driver of
      cocaine-mediated astrocyte antiviral immune responses. Although astrocyte
      antiviral signaling is activated following detection of foreign pathogenic
      material, oxidative stress and increased cytosolic double-stranded DNA (dsDNA)
      can drive antiviral signaling via stimulation of pattern recognition receptors.
      Pretreatment with the glial modulators propentofylline (PPF) or pioglitazone
      (PIO) reversed cocaine-mediated attenuation of astrocyte responses to HIV-1/ZIKV.
      Both PPF/PIO protected against cocaine-mediated generation of reactive oxygen
      species (ROS), increased dsDNA, antiviral signaling pathways and increased type I
      interferon, indicating that cocaine induces astrocyte type I interferon signaling
      in the absence of virus and oxidative stress is a major driver of cocaine
      mediated astrocyte antiviral immunity. Lastly, PPF and PIO have therapeutic
      potential to ameliorate cocaine-mediated dysregulation of astrocyte antiviral
      immunity possibly via a myriad of protective actions including decreases in
      reactive phenotype and damaging immune factors.

PMID- 29578039
TI  - In vivo assessment of the human cerebral microcirculation and its glycocalyx: A
      technical report.
AB  - INTRODUCTION: The cerebral microcirculation and its glycocalyx, a matrix coating
      the luminal endothelium, are key regulators of capillary permeability and
      cerebral blood flow. Microvascular abnormalities are described in several
      neurological disorders. However, assessment of the cerebral microcirculation and
      glycocalyx has mainly been performed ex vivo. NEW METHOD: Here, the technical
      feasibility of in vivo assessment of the human cerebral microcirculation and its
      glycocalyx using sidestream dark field (SDF) imaging is discussed. Intraoperative
      assessment requires the application of a sterile drape covering the camera
      (slipcover). First, sublingual measurements with and without slipcover were
      performed in a healthy control to assess the impact of this slipcover.
      Subsequently, using SDF imaging, the sublingual (reference), cortical, and
      hippocampal microcirculation and glycocalyx were evaluated in patients who
      underwent resective brain surgery as treatment for drug-resistant temporal lobe
      epilepsy. Finally, vessel density, and the perfused boundary region (PBR), a
      validated gauge of glycocalyx health, were calculated using GlycoCheck(c)
      software. RESULTS: The addition of a slipcover affects vessel density and PBR
      values in a control subject. The cerebral measurements in five patients were more
      difficult to obtain than the sublingual ones. This was probably at least partly
      due to the introduction of a sterile slipcover. Results on vessel density and PBR
      showed similar patterns at all three measurement sites. COMPARISON WITH EXISTING
      METHODS: This is the first report on in vivo assessment of the human
      cerebrovascular glycocalyx. Assessment of the glycocalyx is an additional
      application of in vivo imaging of the cerebral microcirculation using SDF
      technique. This method enables functional analysis of the microcirculation and
      glycocalyx, however the addition of a sterile slipcover affects the measurements.
      CONCLUSIONS: SDF imaging is a safe, quick, and straightforward technique to
      evaluate the functional cerebral microcirculation and glycocalyx. Because of
      their eminent role in cerebral homeostasis, this method may significantly add to
      research on the role of vascular pathophysiology underling various neurological
      disorders.

PMID- 29578040
TI  - Evaluation of Vasectomy Trends in the United States.
AB  - OBJECTIVE: To use the Truven Health MarketScan database to better approximate the
      annual rate of vasectomies performed in the US population, to determine changes
      over time, regional differences, providers performing this, and to know if there
      is any monthly variation in vasectomy rates. MATERIALS AND METHODS: Claims data
      were evaluated from 2007 to 2015 to determine the annual prevalence of vasectomy
      by patient age and region in the United States. The cohort included men aged 18
      64 years with at least 1 claim in any given year in Truven Health MarketScan.
      Provider type and place of service were evaluated in 2014 and 2015. Monthly
      evaluation of vasectomy prevalence compared with total claims was performed.
      RESULTS: The prevalence of vasectomies decreased from 2007 to 2015, across all
      age groups and in all locations of the country (P <.001). Using these data and
      the most recent US census data, an estimated 527,476 vasectomies were performed
      in the United States in 2015. The North Central and West regions (0.64% and
      0.60%, respectively) had the highest annual prevalence of vasectomies. The month
      of March and the end of the year had the highest proportion of vasectomies
      performed. In both 2014 and 2015, a urologist in the office setting performed 82%
      of vasectomies. CONCLUSION: An estimated 527,476 vasectomies were performed in
      the United States in 2015. From 2007 to 2015 there was a decrease in the
      proportion of vasectomies performed in all age groups and in all locations of the
      country. The end of the year and the month of March are when the most vasectomies
      are performed.

PMID- 29578041
TI  - Intraoperative Conversion From Partial to Radical Nephrectomy: Incidence,
      Predictive Factors, and Outcomes.
AB  - OBJECTIVE: To evaluate preoperative and intraoperative predictors of conversion
      to radical nephrectomy (RN) in a cohort of patients undergoing a planned partial
      nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: A single-center,
      retrospective review was conducted using our PN database that includes patients
      who were scheduled to undergo PN (regardless of the approach) but were converted
      to RN between August 1990 and December 2016. Reasons for conversion were
      collected from the operative report. Patient demographics and perioperative
      variables were compared with the successful PN group. Univariate and multivariate
      logistic regression analyses were conducted to assess predictors of conversion.
      RESULTS: A total of 1857 patients were scheduled to undergo PN. Of these
      patients, 90 (5%) were converted to RN. The multivariate model showed that larger
      tumor size (odds ratio [OR] = 1.20, P = .040), higher RENAL nephrometry score (OR
      = 1.41, P = .001), hilar tumor or renal sinus invasion (OR = 2.80, P = .004),
      laparoscopic PN (OR = 7.34, P <.001), intraoperative bleeding (OR = 19.62, P
      <.001), positive surgical margin (OR = 31.85, P <.001), and advanced pathologic
      tumor-stage (T3 or T4) (OR = 7.29, P <.001) were associated with increased odds
      of intraoperative conversion to RN. CONCLUSION: The rate of conversion to RN was
      low in patients who were scheduled to undergo PN in this series. Larger tumor
      size with increasing complexity, hilar tumor location or renal sinus invasion,
      locally advanced tumors, laparoscopic PN but not robotic PN, bleeding
      complication, and positive surgical margin were associated with intraoperative
      conversion from scheduled PN to RN.

PMID- 29578042
TI  - Volume and Shape Assessment of Renal Radiofrequency Ablation Lesion.
AB  - OBJECTIVE: To evaluate the microscopic characteristics and quantify the volume of
      a radiofrequency ablation (RFA) lesion. METHODS: Ten male pigs were submitted to
      laparoscopic RFA. An RFA needle was introduced in the lower pole of the left
      kidney to create a lesion expected to be a sphere of 2.0 cm diameter. The animals
      were followed up for 21 days. Kidneys were weighed and the volume was assessed
      using Scherle's method. Cavalieri's principle was used to assess the RFA volume,
      and sphericity was calculated to assess RFA lesion. One sample t test was used to
      compare RFA volume with the volume of a sphere of 2.0 cm diameter, and sphericity
      to hypothetical values of a sphere and an icosahedron. Fragments of RFA region
      were histologically evaluated. RESULTS: Three animals developed postoperative
      complications and were excluded from the analyses. There was no difference in the
      mean weight and volume between right and left kidneys following RFA. The mean
      total volume of RFA injury was 3.44 cm3. There was no difference in the RFA
      volume in comparison with hypothetical volumes of a sphere and an icosahedron of
      2.0 cm diameter. Sphericity of the RFA injury was not similar with a sphere;
      however, it was similar to an icosahedron. Histology revealed areas of
      coagulation necrosis, fibrosis, and inflammatory mononuclear infiltration. Areas
      with normal tissue were also observed. CONCLUSION: The volume of injury caused by
      RFA was as expected and its shape was comparable with an icosahedron. Microscopic
      evaluation revealed areas of normal-appearing tissue.

PMID- 29578043
TI  - No Appendix is Too Short-Simultaneous Mitrofanoff Catheterizable Vesicostomy and
      Malone Antegrade Continence Enema (MACE) for Children with Spina Bifida.
AB  - OBJECTIVE: To present the results of simultaneous creation of both Mitrofanoff
      stoma and Malone antegrade continence stoma (MACE) using simple division of the
      appendix and a cecal extension method. MATERIALS AND METHODS: Between June 2011
      and November 2016, simultaneous Mitrofanoff and MACE was performed in 16 children
      (12 children-simple division of the appendix, 4 children-appendicovesicostomy and
      cecal extension of the appendix). Extension of the appendix was achieved by
      tubularization of the excised cecal flap next to the short appendicular stump.
      The new extended channel was then wrapped by cecal wall. RESULTS: Follow-up was
      40 months (10-74 months). Currently, in all children, both stomas are easily
      catheterizable. Obstruction of MACE occurred in 5 children (4 with split
      appendix, 1 with extended appendix); Mitrofanoff stomal stenosis occurred in 1
      child. Endoscopic revision and prolonged catheterization of stenotic stomas were
      effective in all cases. Wound infection and dehiscence was noted in 2 children
      (both with split appendix). Drainage and intravenous antibiotics were effective.
      All Mitrofanoffs are continent. In 4 children there is incident minor leakage of
      the MACE (3 with split appendix and in 1 with extended appendix). CONCLUSION: The
      split appendix procedure is feasible. Cecal extension of the appendix seems to be
      a good option when the appendix is too short for a simple split procedure.

PMID- 29578044
TI  - Systemic and local adipose tissue in knee osteoarthritis.
AB  - Knee osteoarthritis (OA) is the most common joint disease. Body adipose tissue
      has been shown to be related to the development and progression of knee OA. Among
      systemic adipose tissues, subcutaneous adipose tissue is significantly and
      negatively associated with muscle mass and forces, and could be related to the
      presence and progression of knee OA. Visceral adipose tissue is associated with
      increased cartilage loss and production of pro-inflammatory cytokines. Intra
      muscular adipose tissue is associated with knee osteoarthritic changes, but it
      remains controversial if inter-muscular adipose tissue has a role to play in the
      pathogenesis for knee OA. Knee local adipose tissue such as infrapatellar fat pad
      (IPFP) can interact with neighbouring tissues, and may have a biphasic effect in
      knee OA. The underlying mechanisms for the roles of the systemic and local fat in
      knee OA could be related to biomechanical, metabolic, inflammatory factors and
      fat fibrosis, which may have a separated or combined effect on OA. Tissue
      engineering from systemic or local adipose tissue is a new research direction,
      and adipose tissue-derived stem cells from systemic or local adipose tissue may
      be beneficial for OA cartilage repair. Research on systemic and local adipose
      tissue would provide novel approaches for prevention and treatment of knee OA,
      but further studies are required to explore the roles of different adipose
      tissues in knee OA and the effects of stem cells derived from different adipose
      tissues on knee OA.

PMID- 29578045
TI  - Mutations in osteoprotegerin account for the CCAL1 locus in calcium pyrophosphate
      deposition disease.
AB  - OBJECTIVE: Mutations on chromosomes 5p (CCAL2) and 8q (CCAL1) have been linked to
      familial forms of calcium pyrophosphate deposition disease (CPDD). Mutations in
      the ANKH gene account for CCAL2, but the identity of CCAL1 has been elusive.
      Recently, a single Dutch kindred with a mutation in the Tumor Necrosis Factor
      Receptor Super Family member 11B (TNFRSF11B) gene coding for osteoprotegerin
      (OPG) was described as a gain-of-function mutation. Affected family members had
      premature generalized osteoarthritis (PGOA) and CPDD. As the TNFRSF11B gene is on
      8q, we sought additional evidence that TNFRSF11B was CCAL1, and investigated
      potential disease mechanisms. DESIGN: DNA from two novel PGOA/CPDD families was
      screened for sequence variants in the TNFRSF11B gene. Mutations were verified by
      genotype analysis of affected and unaffected family members. We also investigated
      effects of normal and mutant OPG on regulators of CPP crystal formation in
      porcine cartilage. RESULTS: The identical TNFRSF11B mutation described in the
      Dutch family was present in two novel PGOA/CPDD families. ANKH was normal in
      affected patient fibroblasts. Exogenous OPG did not alter ANKH mRNA or protein
      levels, affect translocation of ANKH to the membrane, nor increase [pyrophosphate
      (PPi)] or other key regulators of CPDD. CONCLUSION: We have firmly established
      the identity of CCAL1 as TNFRSF11B (OPG). Our findings suggest that this mutation
      produces disease in an ANKH-independent manner via novel mechanisms not primarily
      targeting cartilage. This work rationalizes further investigation of OPG pathway
      components as potential druggable targets for CPDD.

PMID- 29578046
TI  - Multi-tissue GAL4-mediated gene expression in all Anopheles gambiae life stages
      using an endogenous polyubiquitin promoter.
AB  - The ability to manipulate the Anopheles gambiae genome and alter gene expression
      effectively and reproducibly is a prerequisite for functional genetic analysis
      and for the development of novel control strategies in this important disease
      vector. However, in vivo transgenic analysis in mosquitoes is limited by the lack
      of promoters active ubiquitously. To address this, we used the GAL4/UAS system to
      investigate the promoter of the An. gambiae Polyubiquitin-c (PUBc) gene and
      demonstrated its ability to drive expression in mosquito cell culture before
      incorporation into An. gambiae transgenic driver lines. To generate such lines,
      piggyBac-mediated insertion was used to identify genomic regions able to sustain
      widespread expression and to create phiC31 docking lines at these permissive
      sites. Patterns of expression induced by PUBc-GAL4 drivers carrying single
      intergenic insertions were assessed by crossing with a novel responder UAS
      mCD8:mCherry line that was created by phiC31-mediated integration. Amongst the
      drivers created at single, unique chromosomal integration loci, two were isolated
      that induced differential expression levels in a similar multiple-tissue spatial
      pattern throughout the mosquito life cycle. This work expands the tools available
      for An. gambiae functional analysis by providing a novel promoter for
      investigating phenotypes resulting from widespread multi-tissue expression, as
      well as identifying and tagging genomic sites that sustain broad transcriptional
      activity.

PMID- 29578048
TI  - De novo transcriptome analysis of immune response on cobia (Rachycentron canadum)
      infected with Photobacterium damselae subsp. piscicida revealed inhibition of
      complement components and involvement of MyD88-independent pathway.
AB  - Cobia, Rachycentron canadum, one of the most important aquatic species in Taiwan,
      has suffered heavy losses from Photobacterium damselae subsp. piscicida, which is
      the causal agent of photobacteriosis. In this study, the transcriptomic profiles
      of livers and spleens from Pdp-infected and non-infected cobia were obtained for
      the first time by Illumina-based paired-end sequencing method with a focus on
      immune-related genes. In total, 164,882 high quality unigenes were obtained in
      four libraries. Following Pdp infection, 7302 differentially expressed unigenes
      from liver and 8600 differentially expressed unigenes from spleen were
      identified. Twenty-seven of the differently expressed genes were further
      validated by RT-qPCR (average correlation coefficient 0.839, p-value <0.01).
      Results indicated a negative regulation of complement components and increased
      expression of genes involved in MyD88-independent pathway. Moreover, a remarkable
      finding was the increased expression of IL-10, implying an inadequacy of immune
      responses. This study not only characterized several putative immune pathways,
      but also provided a better understanding of the molecular responses to
      photobacteriosis in cobia.

PMID- 29578047
TI  - Characterization of a Drosophila glutathione transferase involved in
      isothiocyanate detoxification.
AB  - Glutathione transferases (GSTs) are ubiquitous key enzymes that catalyse the
      conjugation of glutathione to xenobiotic compounds in the detoxification process.
      GSTs have been proposed to play a dual role in the signal termination of insect
      chemodetection by modifying odorant and tasting molecules and by protecting the
      chemosensory system. Among the 40 GSTs identified in Drosophila melanogaster, the
      Delta and Epsilon groups are insect-specific. GSTs Delta and Epsilon may have
      evolved to serve in detoxification, and have been associated with insecticide
      resistance. Here, we report the heterologous expression and purification of the
      D. melanogaster GST Delta 2 (GSTD2). We investigated the capacity of GSTD2 to
      bind tasting molecules. Among them, we found that isothiocyanates (ITC),
      insecticidal compounds naturally present in cruciferous plant and perceived as
      bitter, are good substrates for GSTD2. The X-ray structure of GSTD2 was solved,
      showing the absence of the classical Ser catalytic residue, conserved in the
      Delta and Epsilon GSTs. Using molecular dynamics, the interaction of ITC with the
      GSTD2 three-dimensional structure is analysed and discussed. These findings allow
      us to consider a biological role for GSTD2 in chemoperception, considering GSTD2
      expression in the chemosensory organs and the potential consequences of insect
      exposure to ITC.

PMID- 29578049
TI  - The acute stresses role of the atypical 2-cys peroxiredoxin PmPrx5 in black tiger
      shrimp (Penaeus monodon) from biological immunity and environmental toxicity
      stress.
AB  - As a unique atypical 2-Cys Peroxiredoxin (Prx) of the Prx-like superfamily,
      Peroxiredoxin5 (Prx5) possesses special properties, such as its enzymatic
      mechanism, wide subcellular distribution and high affinity for peroxides and
      peroxynitrite. Prx5 plays a crucial role in oxidative stress, immune responses,
      cell apoptosis, proliferation, differentiation, intracellular signaling, the
      modulation of gene expression, ecdysis, etc. In this paper, we obtained a full
      length Prx5 cDNA sequence (designated PmPrx5) from black tiger shrimp (P.
      monodon). The full-length PmPrx5 cDNA sequence was 1686 bp containing a 5'
      untranslated region (UTR) of 76 bp with two nucleotide sequences (AAA), a 3' UTR
      of 1040 bp with a poly (A) tail and two canonical polyadenylation signal
      sequences (AATAAA), and an open reading frame of 570 bp encoding 189 amino acid
      residues with a predicted molecular mass of 20 kDa and a theoretical isoelectric
      point of 6.29. Phylogenetic trees and multiple sequence alignment showed that the
      PmPrx5 had strong homology with Prx5 proteins from other species, such as
      similarity with Palaemon carinicauda (69%) and Macrobrachium rosenbergii (69%),
      containing the highly conserved functional domain. PmPrx5 mRNA was ubiquitously
      detected in all tested tissues. After P. monodon was exposed to pathogenic
      bacteria, osmotic pressure, acidity and alkalinity and the heavy metal, the mRNA
      expression of PmPrx5 in the gills and hepatopancreas was significantly enhanced
      (P < 0.01) because of the immune response and declined with heavy metal copper
      and cadmium challenges as time progressed. The recombinant PmPrx5 protein
      purified in E. coli (DE3) was further confirmed to exhibit antioxidant activity
      and antibacterial properties to a certain extent using a bacterial growth
      inhibition test in both liquid and solid cultures in vitro. E. coli transformed
      with pRSET-PmPrx5 were dramatically protected in response to metal toxicity
      stress. Thus, PmPrx5 may be developed as a potential therapeutic drug against
      pathogenic bacteria and as a biomarker for pollutant levels. This work offers
      useful clues to further explore the functional mechanism of Prx5 in marine shrimp
      immunity.

PMID- 29578050
TI  - Different roles of crayfish hemocytes in the uptake of foreign particles.
AB  - Crustacean hemocytes are known to remove invading pathogens by phagocytosis. In
      this study, we investigated how the semigranular cells (SGCs) and granular cells
      (GCs) of crayfish Cherax quadricarinatus participated in this process. By
      injecting the animals with excessive amounts of fluorescent microspheres (FMs),
      we showed that only a small portion of the circulating hemocytes were phagocytic
      cells, and they took up FMs in a size-dependent manner. The 0.2 MUm FMs were
      internalized almost entirely by SGCs, while GCs and SGCs both contributed to the
      uptake of 2 MUm FMs. Further analysis of the hemocytes from the animals injected
      with a mixture of FMs suggested that there were a subpopulation of SGCs
      specifically ingesting 0.2 MUm FMs. The size-dependent manner was also applied to
      biological particles. Escherichia coli was internalized by both SGCs and GCs,
      whereas white spot syndrome virus (WSSV) was mostly ingested by SGCs. However,
      the bacterial cells were rapidly taken and cleared from the circulation by the
      hemocytes, while the WSSV virions were gradually internalized and remained in the
      cells for a relatively longer period of time. These findings provide basic
      information of the phagocytic hemocytes of crayfish and how they respond to
      different foreign particles.

PMID- 29578051
TI  - Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during
      postnatal growth of normal and dystrophic (mdx) mouse muscles, and their response
      to taurine treatment.
AB  - Post-natal skeletal muscle growth in mice is very rapid and involves complex
      changes in many cells types over the first 6 weeks of life. The acute onset of
      dystropathology also occurs around 3 weeks of age in the mdx mouse model of the
      human disease Duchenne Muscular Dystrophy (DMD). This study investigated (i)
      alterations in expression patterns of regulatory non-coding RNAs (ncRNAs) in
      vivo, including miRNAs, lncRNAs and tRNAs, during early growth of skeletal
      muscles in normal control C57Bl/10Scsn (C57) compared with dystrophic mdx mice
      from 2 to 6 weeks of postnatal age, and revealed inherent differences in vivo for
      levels of 3 ncRNAs between C57 and mdx muscles before the onset of
      dystropathology. Since the amino acid taurine has many benefits and reduces
      disease severity in mdx mice, this study also (ii) determined the impact of
      taurine treatment on these expression patterns in mdx muscles at the onset of
      dystropathology (3 weeks) and after several bouts of myonecrosis and regeneration
      (6 weeks). Taurine treatment of mdx mice only altered ncRNA levels when
      administered from 18 days to 6 weeks of age, but a deficiency in tRNA levels was
      rectified earlier in mdx skeletal muscles treated from 14 days to 3 weeks.
      Myogenesis in tissue culture was also used to (iii) compare ncRNA expression
      patterns for both strains, and (iv) the response to taurine treatment. These
      analyses revealed intrinsic differences in ncRNA expression patterns during
      myogenesis between strains, as well as increased sensitivity of mdx ncRNA levels
      to taurine treatment.

PMID- 29578052
TI  - Diverse mechanisms of IRF5 action in inflammatory responses.
AB  - Interferon regulatory factor 5 (IRF5) is a key signal-dependent transcription
      factor in myeloid cells. Its expression is induced by granulocyte-macrophage
      colony stimulating factor and interferon-gamma. IRF5 protein is further activated
      in response to stimulation, translocating to the nucleus where it mediates
      inflammatory responses. IRF5 is capable of both the up-regulation of pro
      inflammatory genes and repressing anti-inflammatory mediators, thus polarising
      macrophages to a pro-inflammatory phenotype. We discuss IRF5 interactions with a
      wide range of transcriptional regulators that give rise to its diverse effects at
      the level of chromatin.

PMID- 29578053
TI  - Inhibition of testicular steroidogenesis and impaired differentiation of Sertoli
      cells in peripubertal mice offspring following maternal exposure to BDE-209
      during lactation suppress germ cell proliferation.
AB  - Polybrominated diphenyl ethers (PBDEs) are used for fire prevention purpose. BDE
      209, a congener of PBDEs, is thyroid hormones (THs)-disrupting chemical because
      of its structural similarity with THs. Testis is considered as THs-responsive
      organ and is more susceptible to chemical agents during peripubertal period. This
      study, therefore, evaluated the effect and possible mechanism(s) of action of
      maternal exposure to BDE-209 during lactation on germ cell proliferation,
      testicular steroidogenesis and on differentiation of Sertoli cells (SCs) in
      relation to altered THs status in peripubertal mice offspring. Lactating Parkes
      mice were gavaged with 500 and 700 mg/kg BW of BDE-209 in corn oil from postnatal
      day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive
      controls and vehicle-treated controls. Male pups of lactating dams were
      sacrificed at PND 42. Maternal exposure to BDE-209 during lactation markedly
      affected testicular histopathology, germ cell proliferation and steroidogenesis
      with down-regulated expression of various steroidogenic markers in peripubertal
      mice offspring. Decreased expressions of maturational markers of SCs with a
      decline in serum THs levels were also evident in these offspring. Results thus
      suggest that maternal BDE-209 exposure during lactation impairs germ cell
      proliferation via inhibition of steroidogenic pathway and differentiation of SCs
      in peripubertal mice offspring.

PMID- 29578054
TI  - Silver ions are responsible for memory impairment induced by oral administration
      of silver nanoparticles.
AB  - Increasing use of silver nanoparticles (AgNPs) results in increased human
      exposure. AgNPs are able to cross brain-blood barrier and are a risk factor for
      the brain. Thus, we hypothesized that AgNPs exposure might affect hippocampal
      dependent memory, which required cognitive coordination processes. To verify the
      assumption, in this study we evaluated the effects of orally administered bovine
      serum albumin (BSA)-coated AgNPs on spatial memory, which engage cognitive
      coordination processes for on-going stimuli segregation. Rats following 28 days
      of oral administration with 1 mg/kg (n = 10) or 30 mg/kg (n = 10) BSA-AgNPs or
      saline, a control groups (n = 10, n = 8), were tested with an active place
      avoidance task in the Carousel Maze test. The study revealed significant
      impairment of long- and short-term memory, irrespectively of dose of AgNPs,
      whereas non-cognitive activity was on a similar level. We found significantly
      higher content of silver in the hippocampus in comparison to the lateral cortex.
      No silver was found in the cerebellum and the frontal cortex. The nanoSIMS
      analysis reveal a weak signal of silver in the hippocampus of AgNPs treated
      animals that should be attributed to the presence of silver in ionic form rather
      than AgNPs. Our findings indicate that oral exposure to a low dose AgNPs induces
      detrimental effect on memory and cognitive coordination processes. The presence
      of silver ions rather than AgNPs in different brain regions, in particular the
      hippocampus, suggests crucial role of silver ions in AgNPs-induced impairment of
      the higher brain functions.

PMID- 29578055
TI  - Serum nitric oxide level correlates with serum brain natriuretic peptide and
      whole blood viscosity in hemodialysis patients.
AB  - BACKGROUND: Nitric oxide (NO) is tonically synthesized by the vascular
      endothelium and known as a marker of vasodilatation and blood flow. As NO has a
      critical role in hemodynamics, NO may be associated with other hemodynamics
      related factors including atrial natriuretic peptide (ANP), B-type natriuretic
      peptide (BNP) and whole blood viscosity (WBV). It has been reported that serum NO
      level increased in patients undergoing hemodialysis. However, there are few
      reports about the relationship between NO and hemodynamic parameters in
      hemodialysis patients. OBJECTIVE: We investigated the associations between serum
      levels of NO and other hemodynamics-related factors such as ANP, BNP and WBV in
      patients with hemodialysis. METHODS: NO, ANP, and BNP levels before hemodialysis
      were measured using ELISA method. We measured WBV in pre- and post-dialysis.
      RESULTS: Mean serum levels of NO, ANP, and BNP were 13.97 +/- 10.34 MUg/mL,
      198.85 +/- 61.56 pg/mL, and 1233.32 +/- 280.81 pg/mL, respectively in patients
      with hemodialysis. The mean WBV values at shear rates of 1, 5, and 300 s-1 for
      pre-dialyses were 168.5 +/- 62.5, 76.9 +/- 20.6, and 33.3 +/- 3.8 mP,
      respectively. Serum NO level was positively correlated with WBV at shear rates of
      1, 5, and 300 s-1 at pre- and post-hemodialysis. There is a correlation between
      serum nitrite levels and the change of SBV during hemodialysis. Serum nitrite
      levels correlated with the serum BNP levels. ANP levels have a negative
      correlation with pre-dialytic WBV. However, BNP levels did not correlate with WBV
      during hemodialysis. CONCLUSIONS: WBV is linked to an imbalance in serum
      vasoactive substances in hemodialysis patients and can cause significant
      hemodynamic disturbance.

PMID- 29578056
TI  - Redox regulation of soluble guanylyl cyclase.
AB  - The nitric oxide/soluble guanylyl cyclase (NO-sGC) signaling pathway regulates
      the cardiovascular, neuronal, and gastrointestinal systems. Impaired sGC
      signaling can result in disease and system-wide organ failure. This review seeks
      to examine the redox control of sGC through heme and cysteine regulation while
      discussing therapeutic drugs that target various conditions. Heme regulation
      involves mechanisms of insertion of the heme moiety into the sGC protein, the
      molecules and proteins that control switching between the oxidized (Fe3+) and
      reduced states (Fe2+), and the activity of heme degradation. Modifications to
      cysteine residues by S-nitrosation on the alpha1 and beta1 subunits of sGC have
      been shown to be important in sGC signaling. Moreover, redox balance and
      localization of sGC is thought to control downstream effects. In response to
      altered sGC activity due to changes in the redox state, many therapeutic drugs
      have been developed to target decreased NO-sGC signaling. The importance and
      relevance of sGC continues to grow as sGC dysregulation leads to numerous disease
      conditions.

PMID- 29578058
TI  - The chemical foundations of nitroalkene fatty acid signaling through addition
      reactions with thiols.
AB  - Nitroalkene fatty acids can be formed in vivo and administered exogenously. They
      exert pleiotropic signaling actions with cytoprotective and antiinflammatory
      effects. The presence of the potent electron withdrawing nitro group confers
      electrophilicity to the adjacent beta-carbon. Thiols (precisely, thiolates) are
      strong nucleophiles and can react with nitroalkene fatty acids through reversible
      Michael addition reactions. In addition, nitroalkene fatty acids can undergo
      several other processes including metabolic oxidation, reduction, esterification,
      nitric oxide release and partition into hydrophobic compartments. The signaling
      actions of nitroalkenes are mainly mediated by reactions with critical thiols in
      regulatory proteins. Thus, the thio-Michael addition reaction provides a
      framework for understanding the molecular basis of the biological effects of
      nitroalkene fatty acids at the crossroads of thiol signaling and electrophilic
      lipid signaling. In this review, we describe the reactions of nitroalkene fatty
      acids in biological contexts. We focus on the Michael addition-elimination
      reaction with thiols and its mechanism, and extrapolate kinetic and thermodynamic
      considerations to in vivo settings.

PMID- 29578057
TI  - Inflammatory signaling and metabolic regulation by nitro-fatty acids.
AB  - The addition of nitrogen dioxide (NO2) to the double bond of unsaturated fatty
      acids yields an array of electrophilic nitro-fatty acids (NO2-FA) with unique
      biochemical and signaling properties. During the last decade, NO2-FA have been
      shown to exert a protective role in various inflammatory and metabolic disorders.
      NO2-FA exert their biological effects primarily by regulating two central
      physiological adaptive responses: the canonical inflammatory signaling and
      metabolic pathways. In this mini-review, we summarize current knowledge on the
      regulatory role of NO2-FA in the inflammatory and metabolic response via
      regulation of nuclear factor kappa B (NF-kappaB) and peroxisome proliferator
      activated receptor gamma (PPARgamma), master regulators of inflammation and
      metabolism. Moreover, the engagement of novel signaling and metabolic pathways
      influenced by NO2-FA, beyond NF-kappaB and PPAR signaling, is discussed herein.

PMID- 29578059
TI  - The effect of the electrophilic fatty acid nitro-oleic acid on TRP channel
      function in sensory neurons.
AB  - Nitro-oleic acid (NO2-OA) and related nitroalkenes are electrophilic fatty acid
      derivatives that are present in normal tissues at nanomolar concentrations and
      can increase significantly during inflammation. These substances can suppress
      multiple intracellular signaling pathways contributing to inflammation by
      reversible Michael addition reactions with nucleophilic residues such as cysteine
      and histidine leading to post-translational modification of proteins. NO2-OA also
      can influence inflammation and pain by acting on transient receptor potential
      (TRP) channels in primary sensory neurons. TRPV1, TRPA1 and TRPC can respond to
      electrophilic fatty acids because they have ankyrin-like repeats in their N
      terminus that are rich in cysteine residues that react with electrophiles and
      other thiol modifying species. NO2-OA acts on TRP channels to initially
      depolarize and induce firing in sensory neurons followed by desensitization and
      suppression of firing. In vivo experiments revealed that pretreatment with NO2-OA
      reduces nociceptive behavior evoked by local administration of a TRPA1 agonist
      (AITC) to the rat hind paw. These results raise the possibility that NO2-OA might
      be useful clinically to reduce neurogenic inflammation and certain types of
      painful sensations by desensitizing TRPA1 expressing nociceptive afferents.

PMID- 29578060
TI  - Complete genome sequence of Bacillus licheniformis BL-010.
AB  - The biodegradation of Aflatoxin B1 (AFB1) is an industry of increasing
      importance. Bacillus licheniformis BL-010 was isolated from the aflatoxin
      contaminated corn feed storage, and was shown to degrade AFB1 efficiently. Here
      we present the complete genome sequence of BL-010, the genome comprises 4,287,714
      bp in a circular chromosome with a GC content of 46.12% and contains genes
      encoding AFB1 degrading enzymes. The genome sequence displayed that this strain
      contains genes involved in production of laccase, aromatic ring-opening
      dioxygenase which could detoxify AFB1. Complete genome sequence of the strain BL
      010 can further provide the genomic basis for the biotechnological application of
      strain BL-010 as an effective way to degrade AFB1.

PMID- 29578061
TI  - Mefloquine targets beta-catenin pathway and thus can play a role in the treatment
      of liver cancer.
AB  - The current study was designed and performed to investigate the effect of
      mefloquine on the proliferation and tumor formation potential of liver cancer
      stem cells. CD133 + HepG2 cells were identified using MACS and showed markedly
      higher tumor formation potential compared to the parental cells. The secondary
      tumors formed by CD133 + cells were markedly large in size and more in number
      compared to the parental cells. Mefloquine treatment of CD133 + HepG2 cells
      inhibited the proliferation selectively in concentration based manner. The rate
      of proliferation was inhibited to 82 and 12% in parental and CD133 + sphere
      forming cells, respectively on treatment with 10 MUM concentration of mefloquine.
      The number of secondary tumors formed by primary tumors was decreased
      significantly on treatment with 10 MUM mefloquine concentration. Treatment of the
      liver cancer stem cells with mefloquine markedly decreased the potential to
      undergo self-renewal at 10 MUM concentration after 48 h. The results from western
      blot analysis showed significantly higher expression of cancer stem cell
      molecules beta-catenin and cyclin D1 in LCSCs. Treatment of the LCSCs with
      various concentrations of mefloquine reduced the expression levels of beta
      catenin and cyclin D1. Administration of the CD133 + cell tumor xenografts in the
      mice led to the formation of large sized tumors in the control group. However,
      the tumor growth was inhibited significantly in the mice on treatment with 10
      mg/kg doses of mefloquine after day 21. The tumor weight was significantly lower
      in the animals of mefloquine treatment group compared to the control group. Thus,
      mefloquine treatment inhibits self-renewal and proliferation potential of cells
      through targeting beta-catenin pathway.

PMID- 29578062
TI  - Characterization of essential oil from Ocimum gratissimum leaves: Antibacterial
      and mode of action against selected gastroenteritis pathogens.
AB  - Essential oil of fresh leaves of Ocimum gratissimum (OGEO) was water-steam
      distilled and analyzed by GC-MS. Thirty-seven compounds were identified, with
      eugenol (55.6%) as the major component followed by cis-ocimene (13.9%), gamma
      muurolene (11.6%), (Z,E)-alpha-farnesene (5.6%), alpha-trans-bergamotene (4.1%),
      and beta-caryophyllene (2.7%). Antimicrobial activity of OGEO was tested against
      four gastroenteritis pathogens (Staphylococcus aureus, Escherichia coli,
      Salmonella Typhimurium, and Shigella flexneri). OGEO exhibited antibacterial
      effect, with MICs of 1-2 mg ml-1, against the tested species. OGEO also displayed
      rapid killing effect within 5 s at four times of MIC against both E. coli and S.
      Typhimurium. Various assays were performed to investigate the mode of action of
      the oil. OGEO increased the permeability of microbial cell membrane as evidenced
      by LIVE/DEAD BacLight assay. Analyses of the release of absorbing materials at
      260 nm, protein leakage, SDS-PAGE, and SEM strongly suggested the disruptive
      action of the oil on the cytoplasmic membrane of the tested microorganisms.
      Results revealed that the antibacterial property of OGEO could be due to membrane
      disruption.

PMID- 29578063
TI  - Diversity of virulence genes in Brucella melitensis and Brucella abortus detected
      from patients with rheumatoid arthritis.
AB  - The presence of Brucella melitensis and Brucella abortus genomes were
      investigated in the synovial fluid (SF) samples from 90 patients with rheumatoid
      arthritis (RA). DNA extraction and PCR assay were performed for simultaneous
      identification and discrimination of B. melitensis and B. abortus from the SF
      using three specific primers. After gel electrophoresis, the PCR products were
      confirmed by DNA sequencing. The cbg, omp31, manA, virB, and znuA virulence genes
      typing were performed by multiplex-PCR. Of the 90 samples, 14 were positive for
      B. melitensis (n = 9; 10%) and B. abortus (n = 5; 5.5%). The virulotyping of
      positive samples revealed the presence of all five virulence genes in B.
      melitensis. The virB, cbg, and om31 were detected in all five samples of B.
      abortus. In addition, zhuA and manA were detected in three (60%) and four (80%)
      samples, respectively, of the B. abortus-positive samples. Moreover, a total of
      94.2% and 89.2% of the 14 positive samples were also found positive for manA and
      znuA, respectively. Our findings revealed that the Brucella spp. genomes can be
      detected in the SF of RA patients by the PCR-based method. We thus suggest that
      physicians should consider the Brucella spp. as indicators of potential RA for
      the timely diagnosis and treatment of RA.

PMID- 29578064
TI  - Oscimum sanctum extract inhibits growth of Gram positive and Gram negative
      bacterial strains.
AB  - In the present study petroleum ether, chloroform and methanolic extracts of
      Oscimum sanctum were prepared using soxhlet extractor. The extracts were
      evaluated for antibacterial activity against one Gram positive (Staphylococcus
      aureus) and one Gram negative (Escherichia coli) strain. The activity of the
      extracts was compared with the known antibacterial drugs, Oflaxacin and
      Penicillin G. Disc diffusion method revealed good antibacterial activity of the
      chloroform and methanol extracts compared to the petroleum ether extract.
      Methanolic extract was found to be most active against both Staphylococcus aureus
      and Escherichia coli bacterial strains. The zone of inhibition of methanolic
      extract against Staphylococcus aureus and Escherichia coli at 50 mg concentration
      was 16.0 and 18.0 mm, respectively. Chloroform extract also exhibited good
      antibacterial activity against Staphylococcus aureus and Escherichia coli
      bacterial strains. The zone of inhibition of chloroform extract against
      Staphylococcus aureus and Escherichia coli bacterial strains was 8.0 and 6.0 mm,
      respectively. The zone of inhibition of the drug Penicillin G against Escherichia
      coli and Staphylococcus aureus was18.0 and 17.0 mm, respectively. Oflaxacin
      showed zone of inhibition to be 19.0 and 20.0 against Escherichia coli and
      Staphylococcus aureus, respectively. The petroleum ether extract exhibited no
      activity against any of the two tested bacterial strains. These findings suggest
      that methanolic extract of Oscimum sanctum has anti-bacterial potential and
      therefore should be investigated for phytochemistry.

PMID- 29578065
TI  - Biofilm formation by Salmonella Enteritidis and Salmonella Typhimurium isolated
      from avian sources is partially related with their in vivo pathogenicity.
AB  - Salmonella Enteritidis and Salmonella Typhimurium are among the most prevalent
      serotypes isolated from salmonellosis outbreaks and poultry. Salmonella spp. have
      the capacity to form biofilms on several surfaces, which can favour survival in
      hostile environments, such as slaughterhouses. Salmonella strains present
      differences in pathogenicity. However, there is little information regarding the
      pathogenicity of S. Enteritidis and S. Typhimurium isolated from avian sources
      and their relationship to biofilm production. The aim of this study was to use a
      novel pathogenicity index and a biofilm production assay to evaluate their
      relationships within these serotypes. In addition, we detected the presence of
      the spiA and agfA genes in these strains. Biofilm formation was investigated at
      two temperatures (37  degrees C and 28  degrees C) using microtiter plate assay,
      and the results were compared with the individual pathogenicity index of each
      strain. PCR was used to detect spiA and agfA, virulence genes associated with
      biofilm production. S. Enteritidis and S. Typhimurium strains were capable of
      producing biofilm at 37  degrees C and 28  degrees C. Sixty-two percent and 59.5%
      of S. Enteritidis and 73.8% and 46.2% of S. Typhimurium produced biofilm at 37 
      degrees C and 28  degrees C, respectively. Biofilm production at 37  degrees C
      was significantly higher in both serotypes. Only S. Enteritidis was capable of
      adhering strongly at both temperatures. Biofilm production was related to
      pathogenicity index only at 28  degrees C for S. Enteritidis. spiA and agfA were
      found in almost all strains and were not statistically associated with biofilm
      production.

PMID- 29578066
TI  - The most common spoligotype of Mycobacterium bovis isolated in the world and the
      recommended loci for VNTR typing; A systematic review.
AB  - Mycobacterium bovis is a neglected zoonotic organism that epidemiological studies
      are of crucial importance in identifying its source, control it and prevent it
      from spreading. The aim of this study was to investigate the most common
      spoligotypes of Mycobacterium bovis circulating around the world and introduce
      the most and least strong determine powers of loci for VNTR. We have used
      different databases such as ISC, science direct, Embase (Elsevier), Web of
      Science, Scopus and Medline via PubMed. Searches were performed by key words
      including: Mycobacterium bovis, MIRU -VNTR, spoligotyping and discrimination
      power. Finally, thirty-one articles were selected after filtering out some
      titles, abstracts and full texts. Spoligotype SB0120 was the most common
      circulating type on several continents while SB0121 existed in Europe, Africa and
      America. SB0140 was also detected in Asia, Europe and America. QUB3232 and QUB11b
      were more appropriate loci among the loci with high discriminatory power. MIRU 10
      and MIRU4 were among the loci with poor discriminatory power. Taking the
      published data into consideration, SB0120 and SB0121 are predominant spoligotypes
      of M. bovis circulating among animals around the world. Determining the most
      common spoligotype of M. bovis is the key to find source of infection, control
      and prevent the disease.

PMID- 29578067
TI  - Impact of parenteral antimicrobial administration on the structure and diversity
      of the fecal microbiota of growing pigs.
AB  - While antimicrobials are cost-effective tools for prevention and treatment of
      infectious disease, the impact of their use on potentially beneficent mucosal
      microbial communities of growing pigs has not been widely explored. The objective
      of this study was to characterize the impact of parenteral antibiotics
      administration on the composition and diversity of the resident fecal microbiota
      in growing pigs. Five antimicrobial treatment groups, each consisting of four,
      eight-week old piglets, were administered one of the antimicrobials; Ceftiofur
      Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Oxytetracycline
      (OTC), Procaine Penicillin G (PPG) and Tulathromycin (TUL) at label dose and
      route. Individual fecal swabs were collected immediately before antimicrobial
      administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing.
      Genomic DNA was extracted, and the V1-V3 hypervariable region of 16S rRNA gene
      was amplified and sequenced using Illumina Miseq-based sequencing. Across all
      groups, the most abundant phyla were Firmicutes, Bacteroidetes, and
      Proteobacteria. Linear discriminant analysis and stacked area graphs, showed a
      pronounced, antimicrobial-dependent shift in the composition of fecal microbiota
      over time from day 0. By day 14, the fecal microbial compositions of the groups
      receiving CHC and TUL had returned to a distribution that closely resembled that
      observed on day 0, but differences were still evident. In contrast, animals that
      received PPG, OTC and CCFA, showed a tendency towards a balanced homeostatic
      microbiota structure on day 7, but appeared to deviate away from the day 0
      composition by day 14. Based on our results, the observed changes in fecal
      microbiota showed antimicrobial-specific variation in both duration and extent.
      Understanding the impact of these important antimicrobial-induced changes will be
      a critical step in optimizing the use of antimicrobials in health management
      programs in the swine industry.

PMID- 29578068
TI  - Generation and evaluation of a recombinant Newcastle disease virus strain R2B
      with an altered fusion protein cleavage site as a vaccine candidate.
AB  - Newcastle disease (ND) is a highly contagious and fatal disease of chickens.
      Newcastle disease virus (NDV) strain R2B is an Indian mesogenic strain used for
      secondary vaccination in chickens. Mesogenic strains have increased virulence and
      immunogenicity but may cause disease in vaccinated birds, thus rendering them
      ineffective for use. In this study, we generated a recombinant NDV by changing
      the fusion protein cleavage site of mesogenic rNDV-R2B from a polybasic amino
      acid motif RRQKRF to a dibasic amino acid motif GRQGRL leading to generation of
      an attenuated virus, rNDV-R2B-FPCS. The modified recombinant virus had similar
      growth characteristics as rNDV-R2B, but was less virulent in susceptible
      chickens. Immunization of the recombinant attenuated virus to one week of age SPF
      chickens generated a protective immune response with a substantial reduction in
      virus shed after challenge with virulent NDV. The results of the study indicate
      that the modified rNDV-R2B-FPCS virus can be used for primary immunization in
      birds without any adverse reactions.

PMID- 29578069
TI  - CRISPR-Cas9 genome engineering: Treating inherited retinal degeneration.
AB  - Gene correction is a valuable strategy for treating inherited retinal
      degenerative diseases, a major cause of irreversible blindness worldwide. Single
      gene defects cause the majority of these retinal dystrophies. Gene augmentation
      holds great promise if delivered early in the course of the disease, however,
      many patients carry mutations in genes too large to be packaged into adeno
      associated viral vectors and some, when overexpressed via heterologous promoters,
      induce retinal toxicity. In addition to the aforementioned challenges, some
      patients have sustained significant photoreceptor cell loss at the time of
      diagnosis, rendering gene replacement therapy insufficient to treat the disease.
      These patients will require cell replacement to restore useful vision.
      Fortunately, the advent of induced pluripotent stem cell and CRISPR-Cas9 gene
      editing technologies affords researchers and clinicians a powerful means by which
      to develop strategies to treat patients with inherited retinal dystrophies. In
      this review we will discuss the current developments in CRISPR-Cas9 gene editing
      in vivo in animal models and in vitro in patient-derived cells to study and treat
      inherited retinal degenerative diseases.

PMID- 29578071
TI  - The phagosome and redox control of antigen processing.
AB  - In addition to debris clearance and antimicrobial function, versatile organelles
      known as phagosomes play an essential role in the processing of exogenous antigen
      in antigen presenting cells. While there has been much attention on human
      leukocyte antigen haplotypes in the determination of antigenic peptide
      repertoires, the lumenal biochemistries within phagosomes and endosomes are
      emerging as equally-important determinants of peptide epitope composition and
      immunodominance. Recently, the lumenal redox microenvironment within these
      degradative compartments has been shown to impact two key antigenic processing
      chemistries: proteolysis by lysosomal cysteine proteases and disulfide reduction
      of protein antigens. Through manipulation of the balance between oxidative and
      reductive capacities in the phagosome-principally by modulating NADPH oxidase
      (NOX2) and gamma-interferon-inducible lysosomal thiol reductase (GILT) activities
      studies have demonstrated changes to antigen processing patterns leading to
      modified repertoires of antigenic peptides available for presentation, and
      subsequently, altered disease progression in T cell-driven autoimmunity. This
      review focuses on the mechanisms and consequences of redox-mediated phagosomal
      antigen processing, and the potential downstream implications to tolerance and
      autoimmunity.

PMID- 29578072
TI  - A review on ethnomedicinally important pteridophytes of India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pteridophytes have been considered an excellent
      source of medicine since ancient times and remain underexplored in ethnobotanical
      aspects when compared to other vascular plants. Hence, an attempt has been made
      to compile medicinally important pteridophytes used by different ethnic
      minorities and local people in India. MATERIALS AND METHODS: Relevant information
      on the uses of pteridophytes was extracted from scientific journals (local,
      regional, and international), books, book chapters, conference proceedings, M.Sc.
      and Ph.D. dissertations, and other scientific databases. Recent and accepted
      names of plants were validated using standard nomenclature databases. RESULTS: In
      total, 283 species of pteridophytes are enumerated in this review which are used
      to treat 129 ailments. Ethnobotanical records from the states Madhya Pradesh,
      Tamil Nadu, Assam, Arunachal Pradesh, and Uttarakhand revealed 59% of overall
      uses of pteridophytes from India. Pteridaceae was recorded with highest number of
      medicinally important species (57), followed by Polypodiaceae, Dryopteridaceae,
      Thelypteridaceae, and Aspleniaceae with 36, 27, 22, and 21 species respectively.
      CONCLUSIONS: The use of medicinal plants in the primary healthcare of humans and
      livestock has been documented since ancient times, and they offer a useful source
      of new therapeutics. While pteridophytes have considerable importance in
      traditional pharmacopoeias, scientific studies on pharmacology of this group are
      scanty. Hence, studies on the phytochemistry and pharmacology of medicinally
      important pteridophytes with more citations may reveal active principles that can
      be further developed into novel therapeutic agents. Records of indigenous
      medicinal knowledge about pteridophytes need to be given top priority to aid the
      protection of such knowledge before they vanish from present day traditional
      healers.

PMID- 29578070
TI  - An evolving understanding of the S-glutathionylation cycle in pathways of redox
      regulation.
AB  - By nature of the reversibility of the addition of glutathione to low pKa cysteine
      residues, the post-translational modification of S-glutathionylation sanctions a
      cycle that can create a conduit for cell signaling events linked with cellular
      exposure to oxidative or nitrosative stress. The modification can also avert
      proteolysis by protection from over-oxidation of those clusters of target
      proteins that are substrates. Altered functions are associated with S
      glutathionylation of proteins within the mitochondria and endoplasmic reticulum
      compartments, and these impact energy production and protein folding pathways.
      The existence of human polymorphisms of enzymes involved in the cycle
      (particularly glutathione S-transferase P) create a scenario for inter-individual
      variance in response to oxidative stress and a number of human diseases with
      associated aberrant S-glutathionylation have now been identified.

PMID- 29578073
TI  - De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort
      of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre
      Engraftment Period.
AB  - To investigate rates and outcomes of antibiotic de-escalation during pre
      engraftment neutropenia in allogeneic hematopoietic stem cell transplantation
      (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March
      2014 were analyzed. De-escalation was defined as narrowing the spectrum of
      antibiotic treatment either within (early) or after 96 hours (late) from starting
      antibiotics. Discontinuation, considered a form of de-escalation, was defined as
      stopping antibiotics before engraftment. De-escalation failure was defined as
      restarting/escalating antibiotics within 96 hours after de-escalation. Predictors
      of de-escalation were analyzed. Among 102 patients who started antibiotics and
      were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n =
      58), whereas 34 (33%) received combination therapy (mainly meropenem plus
      glycopeptide, n = 24). Median duration of neutropenia was 17 days. Bloodstream
      infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate
      was 25.5% (n = 26) and mostly consisted of reducing the spectrum of beta-lactams
      (n = 11, 42%). In comparison with theoretical scenario of continuing therapy
      until engraftment, the median savings in terms of antibiotic days were 10 for
      meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of
      early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n = 31)
      and failure rate 19% (6/31). The rate of de-escalation any time before
      engraftment was 55.9% (n = 57), including discontinuation in 33 patients (32%).
      Death at day 60 after HSCT occurred in 3 patients who never underwent de
      escalation. Acute myeloid disease and BSIs were independent predictors of early
      de-escalation. De-escalation, including discontinuation, is feasible and safe in
      pre-engraftment neutropenia after allogeneic HSCT.

PMID- 29578074
TI  - SPHRINT - Printing Drug Delivery Microspheres from Polymeric Melts.
AB  - This paper describes a simple, straightforward, and rapid method for producing
      microspheres from molten polymers by merely printing them in an inkjet-like
      manner onto a superoleophobic surface (microsphere printing, hence SPHRINT).
      Similar to 3D printing, a polymer melt is deposited onto a surface; however, in
      contrast to 2D or 3D printing, the surface is not wetted (i.e. exhibiting high
      contact angles with liquids, above 150 degrees , due to its low surface energy),
      resulting in the formation of discrete spherical microspheres. In this study,
      microspheres were printed using polycaprolactone and poly(lactic-co-glycolic
      acid) loaded with a model active pharmaceutical ingredient-ibuprofen (IBU). The
      formation of microspheres was captured by high-speed imaging and was found to
      involve several physical phenomena characterized by non-dimensional numbers,
      including the thinning and breakup of highly viscous, weakly elastic filaments,
      which are first to be described in pure polymer melts. The resulting IBU-loaded
      microspheres had higher sphericity, reproducible sizes and shapes, and superior
      drug encapsulation efficiencies with a distinctly high process yield (>95%) as
      compared to the conservative solvent-based methods used presently. Furthermore,
      the microspheres showed sustained release profiles.

PMID- 29578075
TI  - The effects of maternal diabetes and insulin treatment on neurogenesis in the
      developing hippocampus of male rats.
AB  - Diabetes in pregnancy is associated with an increasing risk of congenital
      malformations and central nervous system disorders (CNS) especially hippocampal
      neuronal circuitry disruption as a discreet region involved in neurogenesis
      phenomenon. This study aimed to investigate the effect of maternal diabetes and
      insulin treatment on the expression and distribution pattern of NeuN and DCX as
      two important markers of neurogenesis paradigm in developing rat hippocampus. All
      animals were randomly divided into three groups as follows: Control group,
      Diabetic (STZ-D), Diabetic treated with insulin (STZ-INS). Diabetes was induced
      in Wistar female rats by Sterptozotocin intraperitoneal injection (single does).
      Following confirmation of diabetes, animals were mated with non-diabetic males.
      Four to six units of protamine-Zinc insulin were delivered subcutaneously (SC) in
      insulin treated group. At the post-natal day 14 (P14), the brain of male
      offspring's were removed for further study. In fact Immunofluorescence staining
      and Real time - PCR assays are used for evaluation of neurogenesis phenomenon.
      Our results showed a significant higher level of hippocampal DCX expression and
      an increase in the mean number of DCX positive cells in the DG of diabetic group
      male offspring (P < 0.05). We also found an insignificant up-regulation in the
      expression of DCX and the mean number of positive cells in the insulin-treated
      diabetic group neonates as compared to control group (P > 0.05). Nevertheless the
      results of immunofluorescence staining for NeuN also indicated that the mean
      number of NeuN+ cells was significantly lower in dentate gyrus of diabetic group
      male offspring (P < 0.05). Besides, there were significant down- regulation in
      the hippocampal mRNA expression of NeuN in diabetic pups compare to control (P <
      0.05 each). Our results revealed that diabetes during pregnancy has an adverse
      effect on the hippocampal neurogenesis in rat neonates. Furthermore, the control
      of glycemia by insulin is sufficient to prevent the alterations in expression of
      neurogenesis markers.

PMID- 29578076
TI  - Erratum to "Intubation and extubation of the ICU patient" [Anaesth. Crit. Care
      Pain Med. 36 (5) (2017) 327-341].

PMID- 29578077
TI  - How can we best organise communication with patients' families?

PMID- 29578078
TI  - Spinal anaesthesia: What is old? What are the new trends?

PMID- 29578079
TI  - ExtraCorporeal Life support for refractory cardiogenic shock: "An efficient
      system support of peripheral organs more than real ventricular assist device...".

PMID- 29578080
TI  - Endovascular Retrograde Suction Decompression-Assisted Clipping of Large
      Paraclinoid Aneurysm in Hybrid Operating Room: 2-Dimensional Operative Video.
AB  - Surgical treatment of large paraclinoid aneurysms remains technically challenging
      due to the adjacent bony anatomy and neurovascular structures. Endovascular
      retrograde suction decompression using a double-lumen balloon catheter
      facilitates clip ligation of the aneurysm. Video 1 demonstrates a large
      paraclinoid aneurysm that was treated with endovascular balloon occlusion and
      retrograde suction decompression in a hybrid operating room. A 49-year-old woman
      presented with progressively worsening headache. Computed tomography angiography
      demonstrated a large 16-mm left paraclinoid aneurysm. Neurologic examination
      showed no deficits. Angiography with compression of the left carotid artery
      showed the collateral blood flow through the posterior communicating artery. The
      aneurysm was exposed via the pterional transsylvian approach. A double-lumen
      balloon guide catheter was placed in the left internal carotid artery.
      Considering the risk of ischemic complications, the "trapping-evacuation"
      technique was not used. After balloon inflation, a temporary clip was placed on
      the posterior communicating artery. Retrograde suction through the guide catheter
      decreased the intra-aneurysmal pressure. Tandem clipping with fenestrated clips
      was used to occlude the aneurysm and reconstruct the parent artery. Postoperative
      angiography confirmed complete obliteration of the aneurysm, and the patient
      recovered without any neurologic deficits. Endovascular balloon occlusion
      obviated the need for cervical dissection of the internal carotid artery.
      Retrograde suction decompression and intraoperative angiography facilitated
      surgical clipping for large and giant paraclinoid aneurysms.

PMID- 29578081
TI  - Effective cellular internalization, cell cycle arrest and improved
      pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles.
AB  - The present study aims at the development of cholesterol based lipopolymeric
      nanoparticles for improved entrapment, better cell penetration and improved
      pharmacokinetics of Tamoxifen (TMX). Self-assembling cholesterol grafted
      lipopolymer, mPEG-b-(CB-{g-chol}-co-LA) was synthesized from poly(ethyleneglycol)
      block-2-methyl-2-carboxyl-propylenecarboxylic acid-co-poly (l-lactide) [mPEG-b
      (CB-{g-COOH}-co-LA)] copolymer followed by carbodiimide coupling for attaching
      cholesterol. Lipopolymeric nanoparticles were prepared using o/w solvent
      evaporation technique, which were subsequently characterized to determine its
      particle size, entrapment efficiency, release pattern and compared with mPEG-PLA
      nanoparticles. Further, in order to assess the in vitro efficacy, cytotoxicity
      studies, uptake, apoptosis assay and cell cycle analysis were performed in breast
      cancer cell lines (MCF-7 and 4T1). Finally, the pharmacokinetic profile of TMX
      loaded mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles was also performed.
      TMX loaded lipopolymeric nanoparticles of particle size 151.25 +/- 3.74 (PDI
      0.123) and entrapment efficiency of 73.62 +/- 3.08% were formulated. The
      haemolytic index, protein binding and in vitro drug release of the optimized
      nanoparticles were found to be comparable to that of the TMX loaded mPEG-PLA
      nanoparticles. Lipopolymeric nanoparticles demonstrated improved IC50 values in
      breast cancer cells (22.2 MUM in 4T1; 18.8 MUM in MCF-7) than free TMX (27.6 MUM
      and 23.5 MUM respectively) and higher uptake efficiency. At IC50 values, TMX
      loaded lipopolymeric nanoparticles induced apoptosis and cell cycle arrest (G0/G1
      phase) to similar extent as that of free drug. Pharmacokinetic studies indicated
      ~2.5-fold increase in the half-life (t1/2) (p < 0.001) and ~2.7-fold (p < 0.001)
      increase in the mean residence time (MRT) of TMX following incorporation into
      lipopolymeric nanoparticles. Thus, mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric
      nanoparticles offer a more promising approach for delivery of Tamoxifen in breast
      cancer by improving drug internalization and prolonging the mean residence time
      of the drug indicating possibility of dose reduction and hence bypassing the
      adverse effects of TMX therapy.

PMID- 29578082
TI  - Genetics of human and animal uncultivable treponemal pathogens.
AB  - Treponema pallidum is an uncultivable bacterium and the causative agent of
      syphilis (subsp. pallidum [TPA]), human yaws (subsp. pertenue [TPE]), and bejel
      (subsp. endemicum). Several species of nonhuman primates in Africa are infected
      by treponemes genetically undistinguishable from known human TPE strains. Besides
      Treponema pallidum, the equally uncultivable Treponema carateum causes pinta in
      humans. In lagomorphs, Treponema paraluisleporidarum ecovar Cuniculus and ecovar
      Lepus are the causative agents of rabbit and hare syphilis, respectively. All
      uncultivable pathogenic treponemes harbor a relatively small chromosome (1.1334
      1.1405 Mbp) and show gene synteny with minimal genetic differences (>98% identity
      at the DNA level) between subspecies and species. While uncultivable pathogenic
      treponemes contain a highly conserved core genome, there are a number of highly
      variable and/or recombinant chromosomal loci. This is also reflected in the
      occurrence of intrastrain heterogeneity (genetic diversity within an infecting
      bacterial population). Molecular differences at several different chromosomal
      loci identified among TPA strains or isolates have been used for molecular typing
      and the epidemiological characterization of syphilis isolates. This review
      summarizes genome structure of uncultivable pathogenic treponemes including
      genetically variable regions.

PMID- 29578083
TI  - Social geography of Rhinoscleroma and qualitatively and quantitatively abnormal
      cell-mediated immunity.
AB  - Rhinoscleroma is a progressive chronic granulomatous disease of the upper
      respiratory tract that may extend to the tracheobronchial tract. It is common
      belief that the pathology is determined by Klebsiella Rhinoscleromatis. In the
      authors' opinion, the infection with Klebsiella Rhinoscleromatis may not
      represent the only etiopathogenic factor of the disease. Rhinoscleroma is
      reported in many countries, but has a peculiar social and geographic
      distribution, in that it assumes an endemic character only in some regions of the
      Middle East, West Russia, North Africa, Indonesia, Central and South America. In
      Europe, most of the cases are reported in Poland, Hungary and Romania. In Italy,
      Rhinoscleroma is almost exclusively located in the southern and island regions.
      Rhinoscleroma is predominantly reported in rural areas, in the presence of poor
      socio-economic conditions, which according to many authors would be a co-factor
      triggering the disease. In this article, the authors review some inconsistencies
      in etiology, histology and epidemiology of Rhinoscleroma. Based on the overall
      picture, they propose that intrinsic factors, possibly of genetic origin, may
      give rise to the disease, and suggest possible lines of research to distinguish
      between extrinsic and intrinsic factors as determinants for Rhinoscleroma.

PMID- 29578084
TI  - Risk factors and prediction analysis of cutaneous leishmaniasis due to Leishmania
      tropica in Southwestern Morocco.
AB  - Cutaneous leishmaniasis is currently a serious public health problem in northern
      Africa, especially in Morocco. The causative parasite is transmitted to a human
      host through the bite of infected female sandflies of the genus Phlebotomus. The
      objective of the present study is to characterize the causative organisms and to
      predict the risk of cutaneous leishmaniasis (CL) cases in six provinces in
      southwestern Morocco, based on the spatial distribution of cases in relation to
      environmental factors and other risk factors such as socio-economic status and
      demographics. A molecular study was carried out using ITS1 PCR-RFLP method of the
      ribosomal DNA of Leishmania. An epidemiological study on CL cases was reported
      between 2000 and 2016 in this current investigation in six provinces in
      southwestern Morocco. Statistical analysis was performed using a linear
      regression model to identify the impact as well as the interaction between all
      predictor variables on the distribution of CL in the studied provinces. The
      forecast Holt-Winters (HW) method was used to describe the trend and seasonality
      of CL cases. The ITS1-PCR- RFLP analysis revealed the presence of Leishmania
      tropica in all studied provinces. The spatial distribution of CL cases documented
      in all studied provinces during the sixteen years showed a heterogeneous pattern
      and fluctuation trend with an average prevalence of 9.92 per 100,000 inhabitants.
      In addition, the forecast HW model predicts continued variability of trend and
      seasonality of CL cases in the upcoming years. This study confirmed the
      importance of socioeconomic factors, in particular poverty and the vulnerability
      rate, on distribution and emergence of CL. This study revealed a relationship
      between increasing risk of CL occurrence due to Leishmania tropica, as well as
      the distribution and emergence thereof, and socioeconomic factors in the
      investigated area.

PMID- 29578085
TI  - The macroecology of cancer incidences in humans is associated with large-scale
      assemblages of endemic infections.
AB  - It is now well supported that 20% of human cancers have an infectious causation
      (i.e., oncogenic agents). Accumulating evidence suggests that aside from this
      direct role, other infectious agents may also indirectly affect cancer
      epidemiology through interactions with the oncogenic agents within the wider
      infection community. Here, we address this hypothesis via analysis of large-scale
      global data to identify associations between human cancer incidence and
      assemblages of neglected infectious agents. We focus on a gradient of three
      widely-distributed cancers with an infectious cause: bladder (~2% of recorded
      cancer cases are due to Shistosoma haematobium), liver (~60% consecutive to
      Hepatitis B and C infection) and stomach (Helicobacter pylori is associated with
      ~70% of cases). We analyzed countries in tropical and temperate regions
      separately, and controlled for many confounding social and economic variables.
      First, we found that particular assemblages of bacteria are associated with
      bladder cancer incidences. Second, we observed a specific and robust association
      between helminths and liver cancer incidences in both biomes. Third, we show that
      certain assemblages of viruses may facilitate stomach cancer in tropical area,
      while others protect against its development in temperate countries. Finally, we
      discuss the implications of our results in terms of cancer prevention and
      highlight the necessity to consider neglected diseases, especially in tropics, to
      adapt public health strategies against infectious diseases and cancer.

PMID- 29578086
TI  - BaTiO3-core Au-shell nanoparticles for photothermal therapy and bimodal imaging.
AB  - : We report sub-100 nm metal-shell (Au) dielectric-core (BaTiO3) nanoparticles
      with bimodal imaging abilities and enhanced photothermal effects. The
      nanoparticles efficiently absorb light in the near infrared range of the spectrum
      and convert it to heat to ablate tumors. Their BaTiO3 core, a highly ordered non
      centrosymmetric material, can be imaged by second harmonic generation, and their
      Au shell generates two-photon luminescence. The intrinsic dual imaging capability
      allows investigating the distribution of the nanoparticles in relation to the
      tumor vasculature morphology during photothermal ablation. Our design enabled in
      vivo real-time tracking of the BT-Au-NPs and observation of their thermally
      induced effect on tumor vessels. STATEMENT OF SIGNIFICANCE: Photothermal therapy
      induced by plasmonic nanoparticles has emerged as a promising approach to
      treating cancer. However, the study of the role of intratumoral nanoparticle
      distribution in mediating tumoricidal activity has been hampered by the lack of
      suitable imaging techniques. This work describes metal-shell (Au) dielectric-core
      (BaTiO3) nanoparticles (abbreviated as BT-Au-NP) for photothermal therapy and
      bimodal imaging. We demonstrated that sub-100 nm BT-Au-NP can efficiently absorb
      near infrared light and convert it to heat to ablate tumors. The intrinsic dual
      imaging capability allowed us to investigate the distribution of the
      nanoparticles in relation to the tumor vasculature morphology during photothermal
      ablation, enabling in vivo real-time tracking of the BT-Au-NPs and observation of
      their thermally-induced effect on tumor vessels.

PMID- 29578087
TI  - Current approaches in biomaterial-based hematopoietic stem cell niches.
AB  - : Hematopoietic stem cells (HSCs) are multipotent progenitor cells that can
      differentiate and replenish blood and immune cells. While there is a growing
      demand for autologous and allogeneic HSC transplantation owing to the increasing
      incidence of hereditary and hematologic diseases, the low population of HSCs in
      cord-blood and bone marrow (the main source of HSCs) hinders their medical
      applicability. Several cytokine and growth factor-based methods have been
      developed to expand the HSCs in vitro; however, the expansion rate is low, or the
      expanded cells fail to survive upon engraftment. This is at least in part because
      the overly simplistic polystyrene culture substrates fail to fully replicate the
      microenvironments or niches where these stem cells live. Bone marrow niches are
      multi-dimensional, complex systems that involve both biochemical (cells, growth
      factors, and cytokines) and physiochemical (stiffness, O2 concentration, and
      extracellular matrix presentation) factors that regulate the quiescence,
      proliferation, activation, and differentiation of the HSCs. Although several
      studies have been conducted on in vitro HSC expansion via 2D and 3D biomaterial
      based platforms, additional work is required to engineer an effective biomaterial
      platform that mimics bone marrow niches. In this study, the factors that regulate
      the HSC in vivo were explained and their applications in the engineering of a
      bone marrow biomaterial-based platform were discussed. In addition, current
      approaches, challenges, and the future direction of a biomaterial-based culture
      and expansion of the HSC were examined. STATEMENT OF SIGNIFICANCE: Hematopoietic
      stem cells (HSC) are multipotent cells that can differentiate and replace the
      blood and immune cells of the body. However, in vivo, there is a low population
      of these cells, and thus their use in biotherapeutic and medical applications is
      limited (i.e., bone marrow transplantation). In this review, the biochemical
      factors (growth factors, cytokines, co-existing cells, ECM, gas concentrations,
      and differential gene expression) that may regulate the over-all fate of HSC, in
      vivo, were summarized and discussed. Moreover, different conventional and recent
      biomaterial platforms were reviewed, and their potential in generating a
      biomaterial-based, BM niche-mimicking platform for the efficient growth and
      expansion of clinically relevant HSCs in-vitro, was discussed.

PMID- 29578088
TI  - RGD/TAT-functionalized chitosan-graft-PEI-PEG gene nanovector for sustained
      delivery of NT-3 for potential application in neural regeneration.
AB  - : In this study, we prepared a multifunctional gene delivery nanovector
      containing a chitosan (CS) backbone and polyethylenimine (PEI) arms with arginine
      glycine-aspartate (RGD)/twin-arginine translocation (TAT) conjugated via
      polyethylene glycol (PEG). Branched PEI, with a molecular weight of 2000 Da, was
      used to achieve a balance between biocompatibility and transfection efficiency,
      whereas RGD/TAT peptides were conjugated for enhanced targeting ability and
      cellular uptake. Synthesis of the copolymers was confirmed by characterizing the
      chemical structure with 1H nuclear magnetic resonance and Fourier Transform
      Infrared Spectroscopy (FTIR). The nanovector was biocompatible with cells and
      showed excellent capability for DNA condensation; the resulting complexes with
      DNA were well-formed, and possessed small particle size and reasonable positive
      charge. Higher gene transfection efficiency, compared to that achieved with PEI
      (25 kDa), was confirmed in tumor (HeLa cells) and normal cells (293T and NIH 3T3
      cells). More importantly, the cells transfected with the chitosan-graft-PEI
      PEG/pCMV-EGFP-Ntf3 complex produced sustained neurotrophin-3 with a linear
      increase in cumulative concentration, which induced neuronal differentiation of
      neural stem cell and promoted neurite outgrowth. These findings suggested that
      our multifunctional copolymers might be ideal nanovectors for engineering cells
      via gene transfection, and could potentially be applied in tumor therapy and
      regenerative medicine. STATEMENT OF SIGNIFICANCE: We successfully prepared a
      multifunctional gene delivery nanovector containing branched PEI with a molecular
      weight of 2000 Da to balance between biocompatibility and transfection
      efficiency, and RGD/TAT peptides for enhanced targeting ability and cellular
      uptake. The well-formed CPPP/DNA complexes of small particle size and reasonable
      positive charges potentially enhanced gene transfection in both tumor and normal
      cells. More importantly, the CPPP/pCMV-EGFP-Ntf3 complex-transfected 293T cells
      could produce sustained NT-3 with a constant ratio, which induced neuron
      differentiation of NSC and promoted neurite outgrowth. Therefore, our study
      provided an effective strategy for producing neurotrophins by engineering cells
      with gene delivery, which deserved wide investigation and potential application
      in regenerative medicine.

PMID- 29578089
TI  - Research Agenda for the Prevention of Pain and Its Impact: Report of the Work
      Group on the Prevention of Acute and Chronic Pain of the Federal Pain Research
      Strategy.
AB  - : After the 2011 Institute of Medicine report on chronic pain, the Interagency
      Pain Research Coordinating Committee (IPRCC) was created to enhance research
      efforts among federal agencies. The IPRCC and Office of Pain Policy at the
      National Institutes of Health collaborated to identify gaps in knowledge and
      address them via a Federal Pain Research Strategy (FPRS). Interdisciplinary work
      groups (WGs) were established to make research recommendations in 5 areas:
      prevention of acute and chronic pain, acute pain and acute pain management,
      transition from acute to chronic pain, chronic pain and chronic pain management,
      and disparities in pain and pain care; cross-cutting issues were also considered.
      The objective was to provide guidance on current research and to make
      recommendations about addressing identified gaps. Findings from the Prevention of
      Acute and Chronic Pain WG are summarized in this article. The WG created
      subgroups to develop recommendations on specific aspects of prevention of acute
      and chronic pain, including: public education, primary prevention, secondary
      prevention, tertiary prevention, transition from acute to chronic pain, and cross
      cutting mediators. No formal literature review was conducted; however, external
      advisors were available and consulted as needed. Seven key research priorities
      were identified. The one deemed "greatest near-term value" was to optimize public
      health strategies to educate patients on managing pain; that deemed "most
      impactful" was to determine an association between patient and intervention
      factors. Other recommendations were related to the epidemiology of acute pain
      from health care procedures, the epidemiology of acute pain from work-related
      injuries, safety and effectiveness of management of pain associated with health
      care procedures, optimizing approaches to acute postsurgical pain, and safety and
      effectiveness of early interventions for tertiary prevention. Stakeholders,
      including federally sponsored research programs, researchers, health care
      providers, policy makers, patients, and others should work together to implement
      recommendations and address important gaps. PERSPECTIVE: The FPRS Steering
      Committee created 5 WGs to identify research needs and make recommendations in
      key areas of research. This article reports the results of one-the Prevention of
      Acute and Chronic Pain group. Several research priorities emerged, and
      recommendations made to fill existing knowledge gaps.

PMID- 29578090
TI  - Effect on Health Care Costs for Adolescents Receiving Adjunctive Internet
      Delivered Cognitive-Behavioral Therapy: Results of a Randomized Controlled Trial.
AB  - : The economic burden of pediatric chronic pain is high, with an estimated annual
      cost of $19.5 billion. Little is known about whether psychological treatment for
      pediatric chronic pain can alter health care utilization for youth. The primary
      aim of this secondary data analysis was to evaluate the effect of adjunctive
      internet cognitive-behavioral therapy intervention or adjunctive internet
      education on health care-related economic costs in a cohort of adolescents with
      chronic pain recruited from interdisciplinary pain clinics across the United
      States. For the full sample, health care expenditures significantly decreased
      from the year before the intervention to the year after the intervention. Results
      indicated that the rate of change in health care costs over time was not
      significantly different between the internet cognitive-behavioral therapy
      intervention and adjunctive internet education groups. Further research is needed
      to replicate these findings and determine patterns and drivers of health care
      costs for youth with chronic pain evaluated in interdisciplinary pain clinics and
      whether psychological treatments can alter these patterns. This trial was
      registered at clinicaltrials.gov (identifier NCT01316471). PERSPECTIVE: Health
      care expenditures significantly decreased in youth with chronic pain from the
      year before initiating treatment to the following year in both intervention
      conditions, adjunctive internet cognitive-behavioral therapy and adjunctive
      internet education. Contrary to our hypothesis, the rate of change in health care
      costs over time was not significantly different between intervention conditions.

PMID- 29578091
TI  - Clinicopathological and prognostic significance of the RUNX3 expression in
      gastric cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: The relationship between expression of runt related transcription
      factor 3 (RUNX3) and clinicopathological parameters of the patients with gastric
      cancer (GC) is controversial. METHODS: The studies were retrieved from those
      already published essay in PubMed, EMBASE, Wan Fang, CNKI (China National
      Knowledge Infrastructure), the Cochrane Library and Google Scholar. All
      statistical tests in this meta-analysis were performed using Stata 10.0 software
      (Stata Corp, College Station, TX). A P value less than 0.05 was considered
      statistically significant. RESULTS: A total of nine studies involving 796
      patients were included in final meta-analysis. The pooled data showed that
      expression of RUNX3 was significant correlated with tumor's differentiation (OR =
      0.387; 95%CI: 0.237-0.633; P = 0.000), depth of invasion (OR = 0.443; 95%CI:
      0.273-0.717; P = 0.001), lymph node metastasis (OR = 0.394; 95%CI: 0.259-0.598; P
      = 0.000), distant metastasis (OR = 0.403; 95%CI: 0.213-0.764; P = 0.005) and TNM
      stage (OR = 0.461; 95%CI, 0.322-0.659; P = 0.000) in GC. Expression of RUNX3 was
      significant correlated with good overall survival (OS) [1-year OS (OR = 2.735;
      95%CI: 1.966-3.806; P = 0.000), 3-year OS (OR = 4.782; 95%CI: 3.634-6.292; P =
      0.000), 5-year OS (OR = 5.191; 95%CI: 3.775-7.138; P = 0.000]. However, RUNX3 was
      not correlated with gender (OR = 1.409; 95%CI: 0.986-2.014; P = 0.060).
      CONCLUSION: RUNX3 expression correlates with tumor's differentiation, depth of
      invasion, lymph node metastasis, distant metastasis, TNM stage and OS of GC
      patients.

PMID- 29578092
TI  - Quercetin dose affects the fate of hepatic ischemia and reperfusion injury in
      rats: An experimental research.
AB  - BACKGROUND: Quercetin found in fruits and vegetables has an antioxidative effect.
      We aimed to investigate the protective effects of quercetin according to
      different doses on hepatic and ischemia-reperfusion (I/R) injury. METHODS: Fifty
      mature male Sprague-Dawley rats were randomly divided into five groups (n = 10
      for each). All the animal groups underwent laparotomy. Group 1 rats served as a
      sham-operated group. Groups 2-5 underwent 1 h hepatic ischemia and were followed
      by 2 h reperfusion. Group 3-5 animals received an additional intraperitoneal dose
      of 25, 50 or 100 mg/kg quercetin respectively before I/R operation. Blood samples
      were collected for determining serum aspartate transaminase (AST), alanine
      transaminase (ALT) and malondialdehyde (MDA) levels. Also, liver tissue samples
      were taken for measuring of liver MDA concentration and for histopathology
      assessment. RESULTS: The highest levels of biochemical parameters were observed
      in group 2. In quercetin-treated groups, serum AST, ALT, MDA levels, and tissue
      MDA concentration were decreased as inversely with increasing quercetin dose.
      Microscopic evaluation revealed that most conspicuous histological improvement
      was observed in 50 mg/kg quercetin co-treated rats. 25 and 100 mg/kg quercetin co
      treatment could not protect completely against hepatic I/R injury. CONCLUSION:
      Quercetin can be effective in preventing of hepatic I/R injury when the correct
      dose was used.

PMID- 29578093
TI  - WITHDRAWN: Glue versus suture for mesh fixation in inguinal hernia repair.
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- 29578094
TI  - Absorbable versus non-absorbable tacks for mesh fixation in laparoscopic ventral
      hernia repair: A systematic review and meta-analysis.
AB  - OBJECTIVES: To investigate the outcomes of absorbable versus non-absorbable tacks
      in patients undergoing laparoscopic ventral hernia repair. METHODS: We performed
      a systematic review in accordance with Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses statement standards. We conducted a search of
      electronic information sources, including MEDLINE; EMBASE; CINAHL; the Cochrane
      Central Register of Controlled Trials (CENTRAL); the World Health Organization
      International Clinical Trials Registry; ClinicalTrials.gov; and ISRCTN Register,
      and bibliographic reference lists to identify all randomised controlled trials
      (RCTs) and observational studies investigating outcomes of absorbable versus non
      absorbable tacks for mesh fixation in patients undergoing laparoscopic ventral
      hernia repair. We used the Cochrane risk of bias tool and the Newcastle-Ottawa
      scale to assess the risk of bias of RCTs and observational studies, respectively.
      Fixed-effect or random-effects models were applied to calculate pooled outcome
      data. RESULTS: We identified three RCTs and two observational studies enrolling a
      total of 1149 patients. The included patients were comparable in terms of age
      [Mean difference (MD) 0.28, 95% confidence intervals (CI) -1.45-2, P = 0.75],
      male gender (MD 0.81, 95% CI 0.63-1.04, P = 0.10), body mass index (MD -041, 95%
      CI -1.28-0.46, P = 0.36) and hernia defect size (MD 0.12, 95% CI -0.26-0.49, P =
      0.54). The mean and median follow-up period was 30 months and 13 months,
      respectively There was no difference between the two mesh fixation techniques in
      terms of recurrence [Risk difference (RD) 0.03, 95% CI -0.04, 0.09, P = 0.47],
      chronic pain [Odds ratio (OR) 0.91, 95% CI 0.62-1.33, P = 0.64], seroma (OR 0.98,
      95% CI 0.37-2.60, P = 0.96), haematoma (RD -0.00, 95% CI -0.04- 0.04, P = 0.99),
      prolonged ileus (OR 0.99, 95% CI 0.24-4.03, P = 0.99), length of hospital stay
      (MD 0.10, 95% CI -0.36-0.56, P = 0.68) and port-site hernia (OR 0.98, 95% CI 0.13
      7.16, P = 0.98). The operative time was longer in absorbable tack group (MD 7.53,
      95% CI 1.49-13.58, P = 0.01). The results remain consistent when randomised
      trials were analysed separately. CONCLUSIONS: We found no difference in clinical
      outcomes between absorbable and non-absorbable tacks for mesh fixation in
      patients undergoing laparoscopic ventral hernia repair. The quality of the
      available evidence is moderate with a possibility of type 2 error. High quality
      RCTs with adequate statistical power are required to provide more robust basis
      for definite conclusions. Considering the similarity of both techniques in terms
      of clinical outcomes, the cost-effectiveness of each technique would be an
      important outcome determining which technique should be used; this needs to be
      considered as an outcome of interest in future studies.

PMID- 29578095
TI  - The impact of improving teamwork on patient outcomes in surgery: A systematic
      review.
AB  - BACKGROUND: The aviation industry pioneered formalised crew training in order to
      improve safety and reduce consequences of non-technical error. This formalised
      training has been successfully adapted and used to in the field of surgery to
      improve post-operative patient outcomes. The need to implement teamwork training
      as an integral part of a surgical programme is increasingly being recognised. We
      aim to systematically review the impact of surgical teamwork training on post
      operative outcomes. METHODS: Two independent researchers systematically searched
      MEDLINE and Embase in accordance with PRISMA guidelines. Studies were screened
      and subjected to inclusion/exclusion criteria. Study characteristics and outcomes
      were reported and analysed. RESULTS: Our initial search identified 2720 articles.
      Following duplicate removal, title and abstract screening, 107 full text articles
      were analysed. Eight articles met our inclusion criteria. Overall, three articles
      supported a positive effect of good teamwork on post-operative patient outcomes.
      We identified key areas in study methodology that can be improved upon, including
      small cohort size, lack of unified training programme, and short training
      duration, should future studies be designed and implemented in this field.
      CONCLUSION: At present, there is insufficient evidence to support the hypothesis
      that teamwork training interventions improve patient outcomes. We believe that
      non-significant and conflicting results can be attributed to flaws in methodology
      and non-uniform training methods. With increasing amounts of evidence in this
      field, we predict a positive association between teamwork training and patient
      outcomes will come to light.

PMID- 29578096
TI  - Perioperative blood transfusion has no effect on overall survival after
      esophageal resection for esophageal squamous cell carcinoma: A retrospective
      cohort study.
AB  - BACKGROUND: The impact of perioperative blood transfusion (PBT) on the prognosis
      of esophageal cancer patients remains inconclusive. The purpose of this study was
      to assess the association between PBT and survival in esophageal squamous cell
      carcinoma (ESCC) patients. MATERIALS AND METHODS: In this retrospective study,
      patients with ESCC who underwent esophageal resection from January 2008 to
      December 2011 were analyzed. The overall survival and postoperative outcomes
      between PBT and non-PBT patients were compared using Cox regression and
      propensity score matching (PSM) analysis. RESULTS: A total of 935 patients were
      enrolled in this study. Before PSM, the 5-year overall survival rates in PBT and
      non-PBT patients were 48.4% and 56.3% (P = 0.001), respectively. The
      postoperative infection rate in PBT patients was 32.32%, which exceeded the rate
      of 24.22% in non-PBT patients (P = 0.008). PSM created 306 pairs of patients.
      After PSM, the 5-year overall survival rates in PBT and non-PBT patients were
      49.4% and 51.0% (P = 0.334), respectively. The postoperative infection rate in
      PBT patients was 31.04%, which was higher than the rate of 26.47% in non-PBT
      patients (P = 0.105). Multivariable Cox regression analyses showed that PBT was
      not an independent risk factor for overall survival (HR: 0.792, 95% CI: 0.615
      1.021, P = 0.072). CONCLUSION: Perioperative blood transfusion has no effect on
      the overall survival of ESCC patients.

PMID- 29578098
TI  - Influencers and preference predictors of HPV vaccine uptake among US male and
      female young adult college students.
AB  - OBJECTIVE: The purpose of the study was to assess the knowledge, attitudes and
      beliefs of male and female college students in Kentucky about HPV associated
      diseases and vaccines, and to determine which parameters predicted self-reported
      uptake of HPV vaccination. MATERIALS AND METHODS: A self-selected cross-sectional
      sample of college students completed an evidence-based online survey. RESULTS: Of
      approximately 1200 potential respondents, 585 completed the survey. The average
      age was 20.6 (SD 3.15) and 78% were female; 84% of the population had had one or
      more sexual partners. Concern for HPV vaccine safety and potential need for
      boosters did not significantly deter vaccine uptake. Likewise, knowledge about
      HPV associated cancers was not predictive of vaccine uptake. On the other hand,
      parental influence for vaccination was a strong predictor for vaccine uptake (aOR
      = 5.32, 2.71-13.03), and free vaccine nearly doubled the likelihood of being
      vaccinated (aOR 1.90, 1.05-3.41). In addition, the strong preference for the
      respondent's partner to be HPV vaccinated predicted vaccine uptake (aOR = 4.04,
      95% CI: 2.31-7.05), but the lack of preference for partner vaccination predicted
      an unvaccinated self (aOR = 0.50, 0.27-0.93). CONCLUSIONS: HPV vaccination has
      been successful in young adult college students in Kentucky. Young adults prefer
      their partners to be HPV vaccinated regardless of whether they themselves are
      vaccinated. Parental influence and free vaccine were positive predictors for
      vaccine uptake in this population.

PMID- 29578097
TI  - Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18
      years? Results from a cohort study in India.
AB  - Extending two-dose recommendations of HPV vaccine to girls between 15 and 18
      years will reduce program cost and improve compliance. Immunogenicity and vaccine
      targeted HPV infection outcomes were compared between 1795 girls aged 15-18 years
      receiving two (1-180 days) and 1515 girls of same age receiving three (1-60-180
      days) doses. Immunogenicity outcomes in 15-18 year old two-dose recipients were
      also compared with the 10-14 year old three-dose (N = 2833) and two-dose (N =
      3184) recipients. The 15-18 year old two-dose recipients had non-inferior L1
      binding antibody titres at seven months against vaccine-targeted HPV types
      compared to three-dose recipients at 15-18 years and three-dose recipients at 10
      14 years of age. Neutralizing antibody titres at 18 months in 15-18 year old two
      dose recipients were non-inferior to same age three-dose recipients for all
      except HPV 18. The titres were inferior to those in the 10-14 year old three-dose
      recipients for all targeted types. Frequency of incident infections from vaccine
      targeted HPV types in the 15-18 year old two-dose recipients was similar to the
      three dose recipients. None of the girls receiving two or three doses had
      persistent infection from vaccine-targeted types. These findings support that two
      doses of HPV vaccine can be extended to girls aged 15-18 years.

PMID- 29578099
TI  - miR2Pathway: A novel analytical method to discover MicroRNA-mediated dysregulated
      pathways involved in hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs involved in the regulation of gene
      expression at a post-transcriptional level. Recent studies have shown miRNAs as
      key regulators of a variety of biological processes, such as proliferation,
      differentiation, apoptosis, metabolism, etc. Aberrantly expressed miRNAs
      influence individual gene expression level, but rewired miRNA-mRNA connections
      can influence the activity of biological pathways. Here, we define rewired miRNA
      mRNA connections as the differential (rewiring) effects on the activity of
      biological pathways between hepatocellular carcinoma (HCC) and normal phenotypes.
      Our work presented here uses a PageRank-based approach to measure the degree of
      miRNA-mediated dysregulation of biological pathways between HCC and normal
      samples based on rewired miRNA-mRNA connections. In our study, we regard the
      degree of miRNA-mediated dysregulation of biological pathways as disease risk of
      biological pathways. Therefore, we propose a new method, miR2Pathway, to measure
      and rank the degree of miRNA-mediated dysregulation of biological pathways by
      measuring the total differential influence of miRNAs on the activity of pathways
      between HCC and normal states. miR2Pathway proposed here systematically shows the
      first evidence for a mechanism of biological pathways being dysregulated by
      rewired miRNA-mRNA connections, and provides new insight into exploring
      mechanisms behind HCC. Thus, miR2Pathway is a novel method to identify and rank
      miRNA-dysregulated pathways in HCC.

PMID- 29578100
TI  - Wisdom of artificial crowds feature selection in untargeted metabolomics: An
      application to the development of a blood-based diagnostic test for thrombotic
      myocardial infarction.
AB  - INTRODUCTION: Heart disease remains a leading cause of global mortality. While
      acute myocardial infarction (colloquially: heart attack), has multiple proximate
      causes, proximate etiology cannot be determined by a blood-based diagnostic test.
      We enrolled a suitable patient cohort and conducted a non-targeted quantification
      of plasma metabolites by mass spectrometry for developing a test that can
      differentiate between thrombotic MI, non-thrombotic MI, and stable disease. A
      significant challenge in developing such a diagnostic test is solving the NP-hard
      problem of feature selection for constructing an optimal statistical classifier.
      OBJECTIVE: We employed a Wisdom of Artificial Crowds (WoAC) strategy for solving
      the feature selection problem and evaluated the accuracy and parsimony of
      downstream classifiers in comparison with traditional feature selection
      techniques including the Lasso and selection using Random Forest variable
      importance criteria. MATERIALS AND METHODS: Artificial Crowd Wisdom was generated
      via aggregation of the best solutions from independent and diverse genetic
      algorithm populations that were initialized with bootstrapping and a random
      subspaces constraint. RESULTS/CONCLUSIONS: Strong evidence was observed that a
      statistical classifier utilizing WoAC feature selection can discriminate between
      human subjects presenting with thrombotic MI, non-thrombotic MI, and stable
      Coronary Artery Disease given abundances of selected plasma metabolites.
      Utilizing the abundances of twenty selected metabolites, a leave-one-out cross
      validation estimated misclassification rate of 2.6% was observed. However, the
      WoAC feature selection strategy did not perform better than the Lasso over the
      current study.

PMID- 29578101
TI  - Diagnostic accuracy of multiplex real-time PCR approaches compared with
      cultivation -based detection methods: Monitoring the endopathogenic microbiota
      pre and post photo-activated disinfection.
AB  - BACKGROUND: Several microbial species have been implicated in the pathogenesis of
      endodontic diseases that colonize the infected root canal system. Since the
      complete removal of endopathogenic agents is essential in endodontic infection
      therapy, photo-activated disinfection (PAD) is suggested as an alternative method
      to traditional antimicrobial therapy. Recent studies reported that the molecular
      methods with low sensitivity and high efficiency to identify fastidious anaerobic
      endopathogenic microbiota can be replaced by the cultivation-based approaches.
      This study aimed to validate the multiplex real-time PCR in order to identify six
      common microorganisms associated with the endodontic infections before and after
      the PAD. MATERIALS AND METHODS: Microbial specimens from the root canals of 50
      patients with primary and secondary endodontic infections were collected before
      PAD treatment using sterile paper points. Toluidine blue O (TBO)-mediated PAD was
      performed on the root canals, followed by resampling. The prePAD- and postPAD
      treatment endodontic samples were transferred to a transport medium and six
      target microorganisms were then identified from the samples using the
      microbiological culture techniques and multiplex real-time PCR approach. RESULTS:
      Multiplex real-time PCR could represent the presence of all target microorganisms
      in 100% cases before and after the PAD. Before PAD, using the culture method,
      Enterococcus faecalis (100%) was found to be the most frequent, followed by
      Veillonella parvula (97.5%), Aggregatibacter actinomycetemcomitans (94.7%),
      Porphyromonas gingivalis (84.3%), Lactobacillus rhamnosus (84.3%), and
      Actinomyces naeslundii (66.6%); whereas, after PAD these microbial frequencies
      changed to 80%, 83.3%, 66.6%, 80%, 66.6%, and 33.3%, respectively. The
      sensitivity and negative predictive value of the multiplex real-time PCR were
      100% before and after the PAD, whereas the highest and the lowest specificities
      were 100% and 82% before PAD, and 97% and 89% after PAD for E. faecalis and P.
      gingivalis, respectively. The highest (100%) and the lowest (66%) positive
      predictive values were for V. parvula and A. naeslundii before and after the PAD,
      respectively. CONCLUSION: As observed from the results, multiplex real-time PCR
      demonstrated high sensitivity and specificity when compared to the culture
      technique. Therefore, it can prove to be a highly sensitive technique to detect
      the endodontic infections microflora.

PMID- 29578102
TI  - Secondary prevention of chronic musculoskeletal pain: A systematic review of
      clinical trials.
AB  - BACKGROUND: Chronic musculoskeletal pain disorders are highly prevalent and have
      high personal and societal cost. Hence, early detection and care of patients at
      risk of developing chronic pain is important. Risk factors are well known and
      screening tools exist, but much less is known about the care of at-risk patients.
      The aim of this study was to investigate the effectiveness of secondary
      prevention strategies for musculoskeletal pain. METHODS: We performed a
      systematic review of clinical trials in which treatments were adjusted to the
      risk of chronicity in adults with acute or subacute musculoskeletal pain.
      Clinical trials, systematic reviews and meta-analyses published after January 1,
      2000 were searched in PubMed and PEDro databases and in the reference list of
      relevant papers. The risk of bias was assessed by the PEDro score. RESULTS: We
      identified 4807 potentially eligible articles; 13, corresponding to 9 studies,
      met the inclusion criteria. Most studies investigated low back pain. The overall
      risk of bias was moderate, mainly because of the difficulty of blinding in
      physiotherapy studies. As compared with a "one-size-fits-all" treatment,
      stratified programmes showed significant improvements in several domains of the
      International Classification of Functioning, Disability and Health: body
      structures and functions (pain, mood), activities (functional capacity),
      participation (return to work, quality of life), as well as environmental factors
      (healthcare consumption). Effect sizes were moderate. Overall, simple educational
      messages seemed sufficient for low-risk patients. Medium- and high-risk patients
      benefited from a physical reactivation programme combined with education. In high
      risk patients, an additional cognitive-behavioural intervention further improved
      the outcome. CONCLUSIONS: A stratified approach seems effective in reducing long
      term disability in patients with musculoskeletal pain. However, more research is
      necessary to confirm these results.

PMID- 29578103
TI  - Acute bronchodilator therapy does not reduce wasted ventilation during exercise
      in COPD.
AB  - This randomized, double-blind, crossover study aimed to determine if acute
      treatment with inhaled bronchodilators, by improving regional lung hyperinflation
      and ventilation distribution, would reduce dead space-to-tidal volume ratio
      (VD/VT); thus contributing to improved exertional dyspnea in COPD. Twenty COPD
      patients (FEV1 = 50 +/- 15% predicted; mean +/- SD) performed pulmonary function
      tests and symptom-limited constant-work rate exercise at 75% peak-work rate (with
      arterialized capillary blood gases) after nebulized bronchodilator (BD;
      ipratropium 0.5mg + salbutamol 2.5 mg) or placebo (PL; normal saline). After BD
      versus PL: Functional residual capacity decreased by 0.4L (p = .0001). Isotime
      during exercise after BD versus PL (p < .05): dyspnea decreased: 1.2 +/- 1.9 Borg
      units; minute ventilation increased: 3.8 +/- 5.5 L/min; IC increased: 0.24 +/-
      0.28 L and VT increased 0.19 +/- 0.16 L. There was no significant difference in
      arterial CO2 tension or VD/VT, but alveolar ventilation increased by 3.8 +/- 5.5
      L/min (p = .02). Post-BD improvements in respiratory mechanics explained 51% of
      dyspnea reduction at a standardized exercise time. Bronchodilator-induced
      improvements in respiratory mechanics were not associated with reduced wasted
      ventilation - a residual contributory factor to exertional dyspnea during
      exercise in COPD.

PMID- 29578104
TI  - Impact of operative time on early joint infection and deep vein thrombosis in
      primary total hip arthroplasty.
AB  - PURPOSE: Infections and deep vein thrombosis (DVT) after total hip arthroplasty
      (THA) are challenging problems for both the patient and surgeon. Previous studies
      have identified numerous risk factors for infections and DVT after THA but have
      often been limited by sample size. We aimed to evaluate the effect of operative
      time on early postoperative infection as well as DVT rates following THA. We
      hypothesized that an increase in operative time would result in increased odds of
      acquiring an infection as well as a DVT. METHODS: We conducted a retrospective
      analysis of prospectively collected data using the American College of Surgeons
      National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2015
      for all patients undergoing primary THA. Associations between operative time and
      infection or DVT were evaluated with multivariable logistic regressions
      controlling for demographics and several known risks factors for infection. Three
      different types of infections were evaluated: (1) superficial surgical site
      infection (SSI), an infection involving the skin or subcutaneous tissue, (2) deep
      SSI, an infection involving the muscle or fascial layers beneath the subcutaneous
      tissue, and (3) organ/space infection, an infection involving any part of the
      anatomy manipulated during surgery other than the incisional components. RESULTS:
      In total, 103,044 patients who underwent THA were included in our study. Our
      results suggested a significant association between superficial SSIs and
      operative time. Specifically, the adjusted odds of suffering a superficial SSI
      increased by 6% (CI=1.04-1.08, p<0.0001) for every 10-minute increase of
      operative time. When using dichotomized operative time (<90minutes or
      >90minutes), the adjusted odds of suffering a superficial SSI was 56% higher for
      patients with prolonged operative time (CI=1.05-2.32, p=0.0277). The adjusted
      odds of suffering a deep SSI increased by 7% for every 10-minute increase in
      operative time (CI=1.01-1.14, p=0.0335). No significant associations were
      detected between organ/space infection, wound dehiscence, or DVT and operative
      time either as continuous or as dichotomized. CONCLUSION: Prolonged operative
      times (>90min) are associated with increased rates of superficial SSIs, but not
      deep SSIs, organ/space infections, wound dehiscence, or DVT. LEVEL OF EVIDENCE:
      III.

PMID- 29578105
TI  - Arthroscopy-assisted Trillat procedure for anterior shoulder instability:
      Surgical technique and preliminary clinical results.
AB  - The Trillat procedure performed as open surgery to treat anterior shoulder
      instability has been proven effective in preventing recurrences and restoring
      range of motion. An arthroscopically assisted variant of the Trillat procedure is
      described here, together with the preliminary clinical results in 18 patients
      treated between 2011 and 2014. After a mean follow-up of 24.7+/-9.8 months, the
      clinical outcomes were very satisfactory, with a Walch-Duplay score of 81.5+/
      18.0, a Rowe score of 83.6+/-16.0, and 94% of satisfied or very satisfied
      patients. Mean operative time was 55+/-13min. No recurrences were recorded. As an
      easily performed procedure that provides good clinical outcomes, the
      arthroscopically assisted Trillat procedure is a simple and reproducible
      alternative to arthroscopic Latarjet procedure, which is still reserved for
      highly experienced surgical teams.

PMID- 29578106
TI  - Two-team management of vascular injuries concomitant with osteo-articular
      injuries in 36 patients over six years.
AB  - BACKGROUND: Patients with both vascular and osteoarticular injuries require
      multidisciplinary management. Vascular injuries may be function- and/or life
      threatening. The lower limbs are predominantly affected. Traffic, domestic, and
      work-related accidents contribute most of the cases. The primary objective of
      this study was to describe the management of patients with concomitant vascular
      and osteo-articular injuries, with special attention to the rates of amputation
      and fasciotomy. The secondary objective was to suggest a management sequence to
      optimise our surgical practice. HYPOTHESIS: The management sequence is a crucial
      consideration in patients with both vascular and osteo-articular injuries.
      MATERIAL AND METHODS: A 6-year, retrospective, observational study was conducted
      in patients with concomitant vascular and osteo-articular injuries. RESULTS: The
      study included 36 patients with a mean age of 40.6+/-22.1 years. The main sources
      of injury were traffic accidents (n=19, 52.8%), crush injury (n=8, 22.2%), and
      falls (n=5, 13.9%). A compound fracture was present in 20 (55.6%) patients.
      Evidence of ischaemia in 25 (69.4%) patients, and bleeding in 11 (30.6%)
      patients. Pre-operative imaging, by ultrasonography or computed tomography, was
      performed in 27 (75.0%) patients. The lower limb was involved in 30 (83.3%)
      patients, who had osteoarticular injuries to the femur and leg combined with
      injury to the popliteal artery. Fasciotomy was performed in 11 (30.6%) patients
      and secondary amputation in 7 (19.4%) patients. The limb salvage rate was 80.6%.
      Median patient survival was 9.3 [0-74.8] months. DISCUSSION: Coordinated work by
      two surgical teams is crucial to manage concomitant vascular and osteo-articular
      injuries. The management sequence must be defined clearly. Computed tomography
      angiography is the investigation of choice and should be performed at the
      slightest suspicion of vascular injury. LEVEL OF EVIDENCE: IV, retrospective
      observational study.

PMID- 29578107
TI  - Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors
      in 26 Patients With Advanced Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: With expanding indications for programmed death 1 (PD-1) axis
      inhibitors in non-small cell lung cancer (NSCLC), acquired resistance (AR) to
      these therapies is increasingly being encountered. We sought to characterize
      clinical patterns of AR to PD-1 axis inhibitors in patients with advanced NSCLC,
      and evaluate subsequent outcome and management strategies for such patients.
      METHODS: Patients with NSCLC who developed AR to PD-1 axis inhibitor therapy
      initiated between December 2009 and February 2016 at one institution were
      identified and examined by clinical and radiographic features. AR was defined as
      progressive disease after initial response by either Response Evaluation Criteria
      in Solid Tumors v1.1 or immune-related response criteria. RESULTS: Twenty-six
      patients with AR to PD-1 axis inhibitor therapy were identified and evaluated.
      Median time to AR was 313 days; the 2-year survival rate from AR was 70% (95%
      confidence interval: 0.53-0.92). Twenty patients (77%) experienced AR in lymph
      nodes (LNs), including 11 patients with LN-only progression. Twenty-three (88%)
      patients had recurrence limited to one (54%) or two (35%) sites of disease.
      Fourteen patients (54%) continued PD-1 axis inhibitor therapy beyond progression.
      Three patients were re-challenged with the same PD-1 axis inhibitor after holiday
      from and progression off therapy, 2 again responded. Fifteen patients (58%)
      received local therapy to site(s) of AR, 11 continued respective PD-1 axis
      inhibitor after local therapy. The 2-year survival rate from AR among these 15
      patients was 92% (95% confidence interval: 0.77-1). CONCLUSIONS: Acquired
      resistance to PD-1 axis inhibitors is often limited to one or two sites when
      local therapy and continuation of PD-1 axis inhibitor therapy can result in
      prolonged benefit. LN metastases appear to be particularly susceptible sites to
      AR. When progression of disease following response occurs after holiday from PD-1
      axis inhibitor, re-challenge can again lead to tumor regression.

PMID- 29578109
TI  - Center variation in episode-of-care costs for adult spinal deformity surgery:
      results from a prospective, multicenter database.
AB  - BACKGROUND CONTEXT: Adult spinal deformity (ASD) surgery is associated with
      significant resource utilization, costing more than $958 million in charges for
      Medicare patients and more than $1.7 billion in charges for managed care
      population in the last decade. Given the recent move toward bundled payment
      models, it is important to understand the various care components a patient
      receives over the course of a defined clinical episode, its associated cost, and
      the proportion of cost for each component toward the bundled payment. PURPOSE: To
      examine the degree and determinants of variation in inpatient episode-of-care
      (EOC) cost, resource utilization, and patient-reported outcomes for patients
      undergoing ASD surgery across four spine deformity centers in the United States.
      STUDY DESIGN/SETTING: Retrospective analysis of prospective, multicenter
      database. PATIENT SAMPLE: Consecutive patients enrolled in an ASD database from
      four spinal deformity centers. OUTCOME MEASURES: Total in-patient EOC costs and
      Short Form (SF)-6D. METHODS: The study used a multicenter database of 210
      consecutively enrolled operative patients from 2008 to 2013 at four participating
      centers in the United States. Demographic, surgical, and direct cost data,
      expressed in 2013 dollars, for the entire inpatient EOC were obtained from
      administrative databases from the respective hospitals. Mixed models and
      multivariable linear regression were used to evaluate the impact of center on
      total costs adjusting for patient characteristics, length of stay (LOS), and
      surgical factors. RESULTS: A total of 126 patients with complete baseline and 2
      year follow-up data were included. The percentages of patients from each center
      were 36.5%, 7.1%, 24.6%, and 31.7%. Overall, the mean patient age was 58.4+/-12.6
      years, 86% were women, and 94% were Caucasian. The proportion of total cost
      variation explained by the center at which the patient was treated was 17%. After
      adjusting for patient, LOS, and surgical factors the cost variation reduced to
      4%. In multivariable analysis, each additional level fused increased total cost
      variation by $2,500, whereas recombinant human bone morphogenetic protein-2 (BMP)
      use and posterior-only surgical approach lowered total EOC costs by $10,500 and
      $9,400, respectively. No significant difference was observed in 2-year quality
      adjusted life year across centers. CONCLUSIONS: Total EOC costs for ASD surgery
      varied significantly by center. Levels fused, BMP use, and surgical approach were
      the primary drivers of cost variation across centers. Differences in resource
      utilization had no impact on 2-year quality-adjusted life year improvement across
      centers.

PMID- 29578108
TI  - Initiative for Early Lung Cancer Research on Treatment: Development of Study
      Design and Pilot Implementation.
AB  - INTRODUCTION: To maximize the benefits of computed tomographic screening for lung
      cancer, optimal treatment for small, early lung cancers is needed. Limiting the
      extent of surgery spares lung tissue, preserves pulmonary function, and decreases
      operative time, complications, and morbidities. It also increases the likelihood
      of resecting future new primary lung cancers. The goal is to assess alternative
      treatments in a timely manner. METHODS: The focus sessions with patients and
      physicians separately highlighted the need to consider their perceptions.
      Literature reviews and analyses of treatment results using large databases were
      performed to formulate critical questions about long-term treatment outcomes,
      recurrence, and quality of life of alternative treatments. Based on these
      analyses, the investigators developed a prospective multi-institutional cohort
      study, the Initiative for Early Lung Cancer Research for Treatment, to compare
      treatments for stage I NSCLC. HIPAA compliant institutional review board approval
      was obtained and we performed a feasibility study of the first 206 surgical
      patients. RESULTS: Lobectomy was performed in 89 (43.2%) patients, and sublobar
      resection was performed in 117 (56.7%) patients. Mediastinal lymph node resection
      was performed in 173 (84.0%) patients, 8 had N1 and 3 N2 lymph node metastases.
      Patients stated that both the surgeon's opinion (93%) and the patient's own
      opinion (93%) were extremely important, followed by the patients' view that the
      chosen procedure would provide the best quality of life (90%). CONCLUSIONS: It
      was feasible to obtain pre- and postsurgical information from patients and
      surgeons. We anticipate statistically meaningful results about treatment
      alternatives in 3 to 5 years.

PMID- 29578110
TI  - Spontaneous correction of coronal imbalance after selective thoracolumbar-lumbar
      fusion in patients with Lenke-5C adolescent idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Coronal imbalance is a complication of corrective surgeries
      in adolescent idiopathic scoliosis (AIS). However, few studies about immediate
      coronal decompensation in Lenke-5C curves have reported its incidence, prognosis,
      and related factors. PURPOSE: To evaluate the development of coronal imbalance
      after selective thoracolumbar-lumbar (TL/L) fusion (SLF) in Lenke-5C AIS, and to
      reveal related factors. STUDY DESIGN: Retrospective comparative study. PATIENT
      SAMPLE: This study included 50 consecutive patients with Lenke-5C AIS who
      underwent SLF at a single center. OUTCOME MEASURES: Whole-spine anteroposterior
      and lateral radiographs were used to measure radiological parameters. METHODS:
      Patients were divided into two groups according to the presence or absence of
      coronal imbalance (distance between C7 plumb line and central sacral vertical
      line >2 cm) in the early (1 month) postoperative period. Various radiological
      parameters were statistically compared between groups. RESULTS: Of the patients,
      28% (14 of 50) showed coronal imbalance in the early postoperative period;
      however, most of them (13 of 14) showed spontaneous correction during follow-up.
      The development of coronal imbalance was related to less flexibility of the TL/L
      curve (51.3% vs. 52.6%, p=.040), greater T10-L2 kyphosis (11.7 degrees  vs. 6.4
      degrees , p=.034), and greater distal junctional angle (6.0 degrees  vs. 3.7
      degrees , p=.025) in preoperative radiographs. Lowermost instrumented vertebra
      (LIV) tilt was greater in the decompensation [+] group in the early postoperative
      period (8.8 degrees  vs. 4.4 degrees , p=.009). However, this difference
      disappeared in final follow-up with the decrease of LIV tilt in the
      decompensation [+] group. CONCLUSIONS: Less flexibility of the TL/L curve,
      greater TL kyphosis, and greater distal junctional angle preoperatively were
      predictive factors for immediate coronal imbalance in Lenke-5C curves. Although
      coronal imbalance was frequently detected in the early postoperative period after
      SLF, it was mostly corrected spontaneously with a decrease of LIV tilt. Thus, SLF
      for Lenke-5C curves can be a good option regardless of the possible coronal
      imbalance in the early postoperative period.

PMID- 29578111
TI  - Nanoscale linear permittivity imaging based on scanning nonlinear dielectric
      microscopy.
AB  - A nanoscale linear permittivity imaging method based on scanning nonlinear
      dielectric microscopy (SNDM) was developed. The ?C/?z-mode SNDM (?C/?z-SNDM)
      technique described herein employs probe-height modulation to suppress
      disturbances originating from stray capacitance and to improve measurement
      stability. This method allows local permittivity distributions to be examined
      with extremely low noise levels (approximately 0.01 aF) by virtue of the highly
      sensitive probe. A cross-section of a multilayer oxide film was visualized using
      ?C/?z-SNDM as a demonstration, and numerical simulations of the response signals
      were conducted to gain additional insights. The experimental signal intensities
      were found to be in a good agreement with the theoretical values, with the
      exception of the background components, demonstrating that absolute sample
      permittivity values could be determined. The signal profiles near the boundaries
      between different dielectrics were calculated using various vibration amplitudes
      and the boundary transition widths were obtained. The beneficial aspects of
      higher-harmonic response imaging are discussed herein, taking into account
      assessments of spatial resolution and quantitation.

PMID- 29578112
TI  - Quantum tunneling of electron snake states in an inhomogeneous magnetic field.
AB  - In a two dimensional free electron gas subjected to a perpendicular spatially
      varying magnetic field, the classical paths of electrons are snake-like
      trajectories that weave along the line where the field crosses zero. But quantum
      mechanically this system is described by a symmetric double well potential which,
      for low excitations, leads to very different electron behavior. We compute the
      spectrum, as well as the wavefunctions, for states of definite parity in the
      limit of nearly degenerate states, i.e. for electrons sufficiently far from the B
      z   =  0 line. Transitions between the states are shown to give rise to a
      tunneling current. If the well is made asymmetrical by a time-dependent parity
      breaking perturbation then Rabi-like oscillations between parity states occur.
      Resonances can be excited and used to stimulate the transfer of electrons from
      one side of the potential barrier to the other through quantum tunneling.

PMID- 29578113
TI  - Passive magnetic shielding in MRI-Linac systems.
AB  - Passive magnetic shielding refers to the use of ferromagnetic materials to
      redirect magnetic field lines away from vulnerable regions. An application of
      particular interest to the medical physics community is shielding in MRI systems,
      especially integrated MRI-linear accelerator (MRI-Linac) systems. In these
      systems, the goal is not only to minimize the magnetic field in some volume, but
      also to minimize the impact of the shield on the magnetic fields within the
      imaging volume of the MRI scanner. In this work, finite element modelling was
      used to assess the shielding of a side coupled 6 MV linac and resultant
      heterogeneity induced within the 30 cm diameter of spherical volume (DSV) of a
      novel 1 Tesla split bore MRI magnet. A number of different shield parameters were
      investigated; distance between shield and magnet, shield shape, shield thickness,
      shield length, openings in the shield, number of concentric layers, spacing
      between each layer, and shield material. Both the in-line and perpendicular MRI
      Linac configurations were studied. By modifying the shield shape around the linac
      from the starting design of an open ended cylinder, the shielding effect was
      boosted by approximately 70% whilst the impact on the magnet was simultaneously
      reduced by approximately 10%. Openings in the shield for the RF port and beam
      exit were substantial sources of field leakage; however it was demonstrated that
      shielding could be added around these openings to compensate for this leakage.
      Layering multiple concentric shield shells was highly effective in the
      perpendicular configuration, but less so for the in-line configuration. Cautious
      use of high permeability materials such as Mu-metal can greatly increase the
      shielding performance in some scenarios. In the perpendicular configuration,
      magnetic shielding was more effective and the impact on the magnet lower compared
      with the in-line configuration.

PMID- 29578114
TI  - Electrostatic potential in a bent piezoelectric nanowire with consideration of
      size-dependent piezoelectricity and semiconducting characterization.
AB  - Determining the electric potential in a bent piezoelectric nanowire (NW) is a
      fundamental issue of nanogenerators and nanopiezotronics. The combined influence
      of the flexoelectric effect, the semiconducting performance and the angle of
      atomic force microscope (AFM) tip has never been studied previously and will be
      investigated in this paper. The exact solution for the electric potential of a
      bent piezoelectric semiconductor NW is derived. The electric potential of the
      present model with consideration of flexoelectric effect varies along the length
      of the NW and is different from that of the classical piezoelectric model.
      Flexoelectric effect enhances but the semiconducting performance reduces the
      electric potential of the NW. In addition, it is found that if the angle of the
      AFM tip reaches 30 degrees , the error of the electric potential obtained from
      the model ignored the effect of the angle of the AFM tip is almost 16%, which is
      unacceptable.

PMID- 29578115
TI  - Utility of cell-free nucleic acid and circulating tumor cell analyses in prostate
      cancer.
AB  - Prostate cancer is characterized by bone metastases and difficulty of objectively
      measuring disease burden. In this context, cell-free circulating tumor DNA
      (ctDNA) and circulating tumor cell (CTC) quantitation and genomic profiling
      afford the ability to noninvasively and serially monitor the tumor. Recent data
      suggest that ctDNA and CTC quantitation are prognostic for survival. Indeed, CTC
      enumeration using the CellSearch(r) platform is validated as a prognostic factor
      and warrants consideration as a stratification factor in randomized trials.
      Changes in quantities of CTCs using CellSearch also are prognostic and may be
      employed to detect a signal of activity of new agents. Molecular profiling of
      both CTCs and ctDNA for androgen receptor (AR) variants has been associated with
      outcomes in the setting of novel androgen inhibitors. Serial profiling to detect
      the evolution of new alterations may inform drug development and help develop
      precision medicine. The costs of these assays and the small quantities in which
      they are detectable in blood are a limitation, and novel platforms are required
      to address this challenge. The presence of multiple platforms to assay CTCs and
      ctDNA also warrants the consideration of a mechanism to allow comparison of data
      across platforms. Further validation and the continued development and
      standardization of these promising modalities will facilitate their adoption in
      the clinic.

PMID- 29578116
TI  - Seminal plasma miR-192a: a biomarker predicting successful resolution of
      nonobstructive azoospermia following varicocele repair.
AB  - This study was performed to investigate a potential marker for the presence of
      spermatozoa in the ejaculate following varicocelectomy in Chinese men with
      nonobstructive azoospermia and varicoceles. The micro-RNA (miR)-192a levels in
      seminal plasma and testicular tissue were evaluated by quantitative real-time
      polymerase chain reaction from 60 men with nonobstructive azoospermia and
      varicoceles (Group A: 27 men with spermatozoa found in the ejaculate after
      surgery; Group B: 33 men without spermatozoa found in the ejaculate after
      surgery) and 30 controls. The seminal plasma and testicular tissue miR-192a
      levels were higher in Group B than in Group A and the controls (P < 0.001), and
      there was no significant difference between Group A and the controls (P > 0.05).
      Apoptosis and proliferation assays with miR mimics and inhibitors showed that miR
      192a induced GC-2 cell apoptosis through the activation of Caspase-3 protein.
      Thus, seminal plasma miR-192a appears to be a potential marker for successfully
      indicating spermatozoa in the ejaculate following microsurgical varicocelectomy
      in men with nonobstructive azoospermia and varicoceles. Seminal plasma miR-192a
      may be a useful clinical marker for prescreening to determine which patients with
      nonobstructive azoospermia and varicoceles would benefit from varicocelectomy.

PMID- 29578117
TI  - Platelet Distribution Width on Admission Predicts In-Stent Restenosis in Patients
      with Coronary Artery Disease and Type 2 Diabetes Mellitus Treated with
      Percutaneous Coronary Intervention.
AB  - Background: It is known that there is a definite association between platelet
      distribution width (PDW) and poor prognosis in patients with coronary artery
      disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data
      available regarding the prognostic significance of PDW for in-stent restenosis
      (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on
      admission that predicted ISR in patients with CAD and T2DM. Methods: Between
      January 2012 and December 2013, a total of 5232 consecutive patients diagnosed
      with CAD and T2DM undergoing percutaneous coronary intervention were admitted.
      Three years of retrospective follow-up was undertaken. A total of 438 patients
      with second angiography operations were included. ISR was defined as >=50%
      luminal stenosis of the stent or peri-stent segments. Continuous data were
      presented as the mean +/- standard deviation or median (P25, P75) and were
      compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical
      variables were presented as percentages and were compared by Chi-square test or
      Fisher's exact test. The association between PDW and ISR was calculated by
      logistic regression analysis. A two-sided value of P < 0.05 was considered
      statistically significant. Statistical analyses were performed by SPSS version
      22.0 for windows. Results: Fifty-nine patients with ISR, accounting for 13.5% of
      the total, were included. ISR was significantly more frequent in patients with
      higher PDW quartiles compared with lower quartiles. We observed that PDW had a
      strong relationship with mean platelet volume (r = 0.647, 95% confidence interval
      [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves
      showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with
      sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701,
      95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of
      ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]:
      1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more
      than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR:
      4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided
      by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI:
      0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4:
      OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001).
      Conclusion: PDW is an independent predictor of ISR in patients with CAD and T2DM.

PMID- 29578118
TI  - Low-Dose Unfractionated Heparin with Sequential Enoxaparin in Patients with
      Diabetes Mellitus and Complex Coronary Artery Disease during Elective
      Percutaneous Coronary Intervention.
AB  - Background: Despite its limitations, unfractionated heparin (UFH) has been the
      standard anticoagulant used during percutaneous coronary intervention (PCI). This
      study compared the safety of low-dose UFH with sequential enoxaparin with that of
      UFH in patients with diabetes mellitus (DM) and complex coronary artery disease
      receiving elective PCI. Methods: In this retrospective study, 514 consecutive
      patients with atherosclerotic cardiovascular diseases and type 2 DM were admitted
      to the hospital and received selective PCI, from January 2013 to December 2015.
      All patients with PCI received low-dose UFH with enoxaparin (intraductal 50 U/kg
      UFH and 0.75 mg/kg enoxaparin, n = 254; UFH-Enox group) or UFH only (intraductal
      100 U/kg UFH, n = 260; UFH group). The study endpoints were major adverse cardiac
      events (MACEs), namely death, myocardial infarction (MI), stroke, target-vessel
      immediate revascularization (TVR), and thrombolysis in MI (TIMI) major bleeding,
      within 30 days and 1 year after PCI. Any catheter thrombosis during the procedure
      was recorded. Results: Only one patient had an intraductal thrombus in the UFH
      group. At the 30-day follow-up, no MACE occurred in any group; seven and five
      cases of recurrent angina and/or rehospitalization were reported in the UFH-Enox
      and UFH groups, respectively; there was no significant difference between the two
      groups (chi2 = 0.11, P = 0.77). There was no TIMI major bleeding in the groups.
      With respect to the 1-year endpoint, two cases of recurrent MI and two of TVRs
      were reported in the UFH-Enox group, whereas in the UFH group, one case of
      recurrent MI and three of TVRs were reported; no significant difference existed
      between the two groups (chi2 = 0, P = 0.99). There were 30 and 25 recurrent
      angina and/or rehospitalizations in the UFH-Enox and UFH groups, respectively;
      there was no significant difference between the two groups (chi2 = 0.37, P =
      0.57). Conclusion: In elective PCI, low-dose UFH with sequential enoxaparin has
      similar effects and safety to the UFH-only method.

PMID- 29578119
TI  - Molecular Analysis-Based Genetic Characterization of a Cohort of Patients with
      Duchenne and Becker Muscular Dystrophy in Eastern China.
AB  - Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD)
      are common X-linked recessive neuromuscular disorders caused by mutations in
      dystrophin gene. Multiplex polymerase chain reaction (multiplex PCR) and
      multiplex ligation-dependent probe amplification (MLPA) are the most common
      methods for detecting dystrophin gene mutations. This study aimed to contrast the
      two methods and discern the genetic characterization of patients with DMD/BMD in
      Eastern China. Methods: We collected 121 probands, 64 mothers of probands, and 15
      fetuses in our study. The dystrophin gene was detected by multiplex PCR primarily
      in 28 probands, and MLPA was used in multiplex PCR-negative cases subsequently.
      The dystrophin gene of the remaining 93 probands and 62 female potential carriers
      was tested by MLPA directly. In fetuses, multiplex PCR and MLPA were performed on
      4 fetuses and 10 fetuses, respectively. In addition, sequencing was also
      performed in 4 probands with negative MLPA. Results: We found that 61.98% of the
      subjects had genetic mutations including deletions (50.41%) and duplications
      (11.57%). There were 43.75% of mothers as carriers of the mutation. In 15
      fetuses, 2 out of 7 male fetuses were found to be unhealthy and 2 out of 8 female
      fetuses were found to be carriers. Exons 3-26 and 45-52 have the maximum
      frequency in mutation regions. In the frequency of exons individually, exon 47
      and exon 50 were the most common in deleted regions and exons 5, 6, and 7 were
      found most frequently in duplicated regions. Conclusions: MLPA has better
      productivity and sensitivity than multiplex PCR. Prenatal diagnosis should be
      applied in DMD high-risk fetuses to reduce the disease incidence. Furthermore, it
      is the responsibility of physicians to inform female carriers the importance of
      prenatal diagnosis.

PMID- 29578120
TI  - Central Nervous System Involvement in Hemophagocytic Lymphohistiocytosis in
      Adults: A Retrospective Analysis of 96 Patients in a Single Center.
AB  - Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening
      clinical syndrome. Central nervous system (CNS) involvement is a severe
      complication, which can lead to rapid disease development and higher morality.
      However, this has not been given enough attention in adult HLH. Therefore, we
      carried out this study to analyze the clinical features, laboratory findings,
      treatment outcomes, and other characteristics of adult HLH with CNS involvement.
      Methods: A retrospective analysis of 96 adult patients with HLH combined with CNS
      involvement between June 2003 and December 2016 was conducted. Clinical features,
      cerebrospinal fluid (CSF) features, image changes, and therapeutic outcomes were
      analyzed. Results: Among the 96 patients, 86 had various CNS symptoms and 33
      (38.4%) had already presented symptoms before the HLH diagnosis was confirmed. A
      total of 59 patients received CSF examinations and showed abnormalities in 23
      patients (39.0%). Seventy patients received imaging examinations and the results
      showed fifty patients with imaging changes (71.4%). Fifty-seven patients received
      multiple rounds of repeated intrathecal injection therapy and 35 patients
      improved (61.4%). As for the multiple analyses of effective factors on survival
      time, the results showed that the effects of combined Epstein-Barr virus (EBV)
      infection (P = 0.026, Exp(B) = 2.309, 95% confidence interval [CI] [1.108, 4.823)
      and intrathecal injection therapy (P = 0.013, Exp(B) = 0.422, 95% CI [0.214,
      0.831]) on the survival time of the CNS-HLH patients were significant.
      Conclusions: Complication with EBV infection is a risk factor, and intrathecal
      injection is a protective factor. CNS involvement in HLH is not rare, which can
      result in a poor prognosis. Multiple rounds of repeated intrathecal injection
      therapy can improve the prognosis of CNS-HLH patients.

PMID- 29578121
TI  - A Retrospective Study Comparing Surgical and Early Oncological Outcomes between
      Intracorporeal and Extracorporeal Ileal Conduit after Laparoscopic Radical
      Cystectomy from a Single Center.
AB  - Background: Robot-assisted/laparoscopic intracorporeal ileal conduit (ICIC) has
      been reported in many experienced centers. Whether laparoscopic ICIC is superior
      to extracorporeal ileal conduit (ECIC) and whether laparoscopic ICIC should be
      promoted is still controversial. The aim of the study was to compare surgical and
      early oncological outcomes between patients undergoing laparoscopic radical
      cystectomy (LRC) with ICIC and ECIC. Methods: From January 2011 to June 2016, a
      total of 45 patients with bladder cancer underwent LRC with ileal conduit at our
      department, of whom 20 patients underwent LRC with ECIC and 25 patients underwent
      LRC with ICIC. Data of each patient's characteristics, surgical outcomes, and
      short-term oncological outcomes were collected and analyzed. Results: LRC with
      ileal conduit was performed successfully on all 45 patients. There were no
      significant differences in patients' characteristics, mean total operative time,
      and mean estimated blood loss between the ICIC and ECIC groups. Median time of
      flatus and oral intake was shorter in the ICIC group compared with the ECIC group
      (3 vs. 5 days, P = 0.035; 4 vs. 5 days, P = 0.002). The complications rates did
      not show significant difference between the two groups within the first 90 days
      postoperatively (P = 0.538). Cancer staging showed 45% of patients in the ECIC
      group and 36% in the ICIC group had a pathologic stage of T3 or T4, and 50% of
      patients in the ECIC group and 44% in the ICIC group had a pathologic stage of N1
      or N1+. Kaplan-Meier analysis showed no significant difference in overall
      survival at 24 months (60% vs. 62%, P = 0.857) between the ECIC and ICIC groups.
      Conclusions: ICIC after LRC may be successful with the benefits of faster
      recovery time. No significant difference was found in complications and
      oncological outcomes between ICIC and ECIC. However, larger series with longer
      follow-up are needed to validate this procedure.

PMID- 29578122
TI  - Efficacy and Safety of Unmanipulated Haploidentical Related Donor Allogeneic
      Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory
      Acute Myeloid Leukemia.
AB  - Background: Studies of haploidentical-related donor (HRD) stem cell
      transplantation using a combination of peripheral blood stem cells (PBSCs) and
      bone marrow as the graft have reported encouraging results for patients with
      hematological diseases. However, few studies specifically reported
      transplantation of only PBSCs from HRDs among patients with relapsed or
      refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side
      effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for
      relapsed/refractory AML were analyzed. Methods: We performed a retrospective
      analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT
      from HRDs (n = 36). Results: Thirty-one (86.1%) patients in the HRD-PBSCT group
      achieved platelet recovery. The cumulative incidence of acute graft-versus-host
      disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence
      of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD
      PBSCT group had recurrent disease at a median of 183 days after transplantation
      (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5
      years. On multivariate analysis, donor age and patient age >40 years were
      independent risk factors for inferior disease-free survival or overall survival
      (P < 0.05). The results of the present study demonstrate rapid and complete
      neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising
      survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating
      factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT
      under myeloablative conditioning when no matched sibling donor is available.
      Conclusions: Our results support the feasibility, effectiveness, and tolerability
      of PBSCs as a graft source in unmanipulated HRD transplantation under
      myeloablative conditioning in patients with leukemia.

PMID- 29578123
TI  - A Novel SLC20A2 Mutation Associated with Familial Idiopathic Basal Ganglia
      Calcification and Analysis of the Genotype-Phenotype Association in Chinese
      Patients.
AB  - Background: Idiopathic basal ganglia calcification (IBGC) is a genetic disorder
      characterized by bilateral basal ganglia calcification and neural degeneration.
      In this study, we reported a new SLC2OA2 mutation of IBGC and reviewed relevant
      literature to explore the association between phenotypes and genotypes in Chinese
      IBGC patients. Methods: Clinical information of the proband and her relatives
      were collected comprehensively. Blood samples of both the patient and her father
      were obtained, and genetic screening related to IBGC was performed using second
      generation sequencing with their consent. Findings were confirmed by Sanger
      sequencing. Polyphen-2 was used to predict the potential association between
      mutations and disease. Then, we retrieved literatures of Chinese IBGC patients
      and explored the association between phenotype and genotype. Results: A novel
      mutation was identified through genetic testing, and it is suggested to be a
      damage mutation predicted by Polyphen-2. Through literature review, we found that
      SLC20A2 mutation is the most common cause for IBGC in China. Its hot spot regions
      are mainly on the 1st and 8th exons; the second common one is PDGFB where the hot
      spot covered a length of 220-230 bp localized on the 2nd exon; moreover, Chinese
      IBGC patients featured early-onset, more severe movement disorder and relatively
      mild cognitive impairment compared with those in other countries. Conclusions:
      There is significant heterogeneity both in phenotype and genotype in Chinese IBGC
      patients. Further research of pathogenic mechanism of IBGC is required to
      eventually develop precise treatment for individuals who suffered this disease.

PMID- 29578124
TI  - Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation
      in ventilator-induced lung injury.
AB  - Background: Ventilator-induced lung injury (VILI) is commonly associated with
      barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI,
      but its role has not been fully elucidated. This study examined the relationship
      between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]
      alpha, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were
      ameliorated by glutamine in VILI, both in vitro and in vivo. Methods: For the in
      vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into
      five groups with random number table (n = 6 in each group): control (Group C);
      low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high
      tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in
      all groups, except Group C, underwent mechanical ventilation for 4 h. For the in
      vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine
      underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were
      obtained to detect the junction proteins, inflammatory cytokines, and lung
      pathological changes by the Western blotting, cytokine assay, hematoxylin and
      eosin staining, and immunofluorescence. Results: In vivo, compared with Group C,
      total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = 
      28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-alpha (t = -19.812, P <
      0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P <
      0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group
      H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t =
      10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group
      H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the
      percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01),
      and TNF-alpha (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G;
      IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = 
      14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group
      H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = 
      21.111, P < 0.01) and TNF-alpha (t = -15.270, P < 0.01) were increased in the 20%
      cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the
      expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P <
      0.01) were decreased in the 20% cyclic stretching group. Compared with the
      stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-alpha (t =
      8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = 
      3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and
      p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.
      Conclusions: High tidal volume mechanical ventilation and 20% cyclic stretching
      could cause VILI. Glutamine regulates VILI by improving cytokines and increasing
      the adherens junctions, protein E-cadherin and p120-catenin, to enhance the
      epithelial barrier function.

PMID- 29578125
TI  - In vitro Effects of Nerve Growth Factor on Cardiac Fibroblasts Proliferation,
      Cell Cycle, Migration, and Myofibroblast Transformation.
AB  - Background: Recent research indicates that nerve growth factor (NGF) promotes
      cardiac repair following myocardial infarction by promoting angiogenesis and
      cardiomyocyte survival. The purpose of this study was to investigate the effects
      of NGF on cardiac fibroblasts (CFs) proliferation, cell cycle, migration, and
      myofibroblast transformation in vitro. Methods: CFs were obtained from ventricles
      of neonatal Sprague-Dawley rats and incubated with various concentrations of NGF
      (0, 0.01, 0.1, 1, 10, and 100 ng/ml; 0 ng/ml was designated as the control
      group). Cell proliferation and cell cycle of the CFs were measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry
      (FCM), respectively. A cell scratch wound model and transwell were carried out to
      observe effects of NGF on migration of CFs after 24 h of culture. Real-time
      polymerase chain reaction (RT-PCR) and Western blotting were used to measure
      alpha-smooth muscle actin (alpha-SMA) at mRNA and protein levels after CFs were
      incubated with various concentrations of NGF. Results: Expression of alpha-SMA
      measured by RT-PCR and Western blotting significantly increased in the 1 and 10
      ng/ml NGF groups (P < 0.05). Absorbance values of CFs showed that NGF did not
      influence the proliferation of CFs (The A490values were 0.178 +/- 0.038, 0.182 +/
      0.011, 0.189 +/- 0.005, 0.178 +/- 0.010, 0.185 +/- 0.025, and 0.177 +/- 0.033,
      respectively, in the 0, 0.01, 0.1, 1, 10, and 100 ng/ml NGF groups [P = 0.800,
      0.428, 0.981, 0.596, and 0.913, respectively, compared with control group]), and
      FCM analysis showed that the percentage of CFs in G0/G1, S, and G2/M phases was
      not changed (P > 0.05). The cell scratch wound model and transwell showed that
      CFs migration was not significantly different (P > 0.05). Conclusion: NGF induces
      myofibroblast transformation but does not influence proliferation, cell cycle, or
      migration of CFs in vitro.

PMID- 29578126
TI  - Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in
      Kidney Transplant Recipients: A Network Meta-Analysis of Randomized Controlled
      Trials.
AB  - Background: Mineral and bone disorder is one of the severe complications in
      kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates
      had favorable effects on bone mineral density (BMD). We sought to compare
      different bisphosphonate regimens and rank their strategies. Methods: We searched
      PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL)
      up to April 01, 2017, for randomized controlled trials (RCTs) comparing
      bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We
      executed the tool recommended by the Cochrane Collaboration to evaluate the risk
      of bias. We performed pairwise meta-analyses using random effects models and
      network meta-analysis (NMA) using Bayesian models and assessed the quality of
      evidence. Results: A total of 21 RCTs (1332 participants) comparing 6
      bisphosphonate regimens were included. All bisphosphonates showed a significantly
      increased percentage change in BMD at the lumbar spine compared to calcium except
      clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in
      comparison to clodronate with calcium (mean difference [MD], 9.84; 95%
      credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D
      analogs had a significantly lower influence than adding either pamidronate or
      alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24,
      respectively). In terms of percentage BMD change at the femoral neck, both
      pamidronate and ibandronate combined with calcium demonstrated a remarkable gain
      compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32
      14.22, respectively). The combination of ibandronate with calcium displayed a
      significant increase in absolute BMD compared to any other treatments and was
      ranked best. Conclusions: Our NMA suggested that new-generation bisphosphonates
      such as ibandronate were more favorable in KTRs to improve BMD. However, the
      conclusion should be treated with caution due to indirect comparisons.

PMID- 29578127
TI  - Mindfulness Meditation for Primary Headache Pain: A Meta-Analysis.
AB  - Background: Several studies have reported that mindfulness meditation has a
      potential effect in controlling headaches, such as migraine and tension-type
      headache; however, its role remains controversial. This review assessed the
      evidence regarding the effects of mindfulness meditation for primary headache
      pain. Methods: Only English databases (PubMed, Cochrane Central Register of
      Controlled Trials [the Cochrane Library], PsycINFO, Psychology and behavioral
      science collection, PsyArticles, Web of Science, and Scopus) were searched from
      their inception to November 2016 with the keywords ("meditation" or "mindfulness"
      or "vipassana" or "dzogchen" or "zen" or "integrative body-mind training" or
      "IBMT" or "mindfulness-based stress reduction" or "MBSR" or "mindfulness-based
      cognitive therapy" or "MBCT" and "Headache" or "Head pain" or "Cephalodynia" or
      "Cephalalgia" or "Hemicrania" or "Migraine"). Titles, abstracts, and full-text
      articles were screened against study inclusion criteria: controlled trials of
      structured meditation programs for adult patients with primary headache pain. The
      quality of studies included in the meta-analysis was assessed with the Yates
      Quality Rating Scale. The meta-analysis was conducted with Revman 5.3. Results:
      Ten randomized controlled trials and one controlled clinical trial with a
      combined study population of 315 patients were included in the study. When
      compared to control group data, mindfulness meditation induced significant
      improvement in pain intensity (standardized mean difference, -0.89; 95%
      confidence interval, -1.63 to -0.15; P = 0.02) and headache frequency (-0.67; 
      1.24 to -0.10; P = 0.02). In a subgroup analysis of different meditation forms,
      mindfulness-based stress reduction displayed a significant positive influence on
      pain intensity (P < 0.000). Moreover, 8-week intervention had a significant
      positive effect (P < 0.000). Conclusions: Mindfulness meditation may reduce pain
      intensity and is a promising treatment option for patients. Clinicians may
      consider mindfulness meditation as a viable complementary and alternative medical
      option for primary headache.

PMID- 29578129
TI  - DNA Methylation and Uveal Melanoma.
AB  - Objective: The objective of the study was to summarize the role of DNA
      methylation in the development and metastasis of uveal melanoma (UM). Data
      Sources: The relevant studies in MEDLINE were searched. Study Selection: In this
      review, we performed a comprehensive literature search in MEDLINE using "uveal
      melanoma" AND ("DNA methylation" OR "epigenetics") for original research/review
      articles published before February 2018 on the relationship between DNA
      methylation and UM. References of the retrieved studies were also examined to
      search for potentially relevant papers. Results: Previous studies on the
      relationship between DNA methylation and UM covered many genes including tumor
      suppressor genes (TSGs), cyclin-dependent kinase genes, and other genes. Among
      them, the TSG genes such as RASSF1A and p16INK4a, which encodes a cyclin
      dependent kinase inhibitor, are relatively well-studied genes. Specifically, a
      high percentage of promoter methylation of RASSF1A was observed in UM cell lines
      and/or patients with UM. Promoter methylation of RASSF1A was also associated with
      the development of metastasis. Similarly, a high percentage of promoter
      hypermethylation of p16INK4a was found in UM cell lines. DNA promoter methylation
      can control the expression of p16INK4a, which affect cell growth, migration, and
      invasion in UM. Many other genes might also be involved in the pathogenesis of UM
      such as the Ras and EF-hand domain containing (RASEF) gene, RAB31, hTERT,
      embryonal fyn-associated substrate, and deleted in split-hand/split-foot 1.
      Conclusions: Our review reveals the complex mechanisms underlying the
      tumorigenesis of UM and highlights the great needs of future studies to discover
      more genes/5'-C-phosphate-G-3' sites contributing to the development/metastasis
      of UM and explore the mechanisms through which epigenetic changes exert their
      function in UM.

PMID- 29578128
TI  - Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting
      Cardiomyocyte Autophagy.
AB  - Objective: Hydrogen sulfide (H2S), a gaseous signal molecule, plays a crucial
      role in many pathophysiologic processes in the cardiovascular system. Autophagy
      has been shown to participate in the occurrence of many cardiac diseases.
      Increasing evidences indicated that H2S regulates myocardial structure and
      function in association with the altered autophagy and plays a "switcher" role in
      the autophagy of myocardial diseases. The aim of this review was to summarize
      these insights and provide the experimental evidence that H2S targets
      cardiomyocyte autophagy to regulate cardiovascular function. Data Sources: This
      review was based on data in articles published in the PubMed databases up to
      October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy,"
      and "cardiovascular diseases." Study Selection: Original articles and critical
      reviews on H2S and autophagy were selected for this review. Results: When
      autophagy plays an adaptive role in the pathogenesis of diseases, H2S restores
      autophagy; otherwise, when autophagy plays a detrimental role, H2S downregulates
      autophagy to exert a cardioprotective function. For example, H2S has beneficial
      effects by regulating autophagy in myocardial ischemia/reperfusion and plays a
      protective role by inhibiting autophagy during the operation of cardioplegia and
      cardiopulmonary bypass. H2S postpones cardiac aging associated with the
      upregulation of autophagy but improves the left ventricular function of smoking
      rats by lowering autophagy. Conclusions: H2S exerts cardiovascular protection by
      regulating autophagy. Cardiovascular autophagy would likely become a potential
      target of H2S therapy for cardiovascular diseases.

PMID- 29578131
TI  - Painless Colonoscopy: A Pilot Study of a 5.9-mm Endoscope for Routine
      Colonoscopy.

PMID- 29578130
TI  - Is Human-induced Pluripotent Stem Cell the Best Optimal?
AB  - Objective: Since the advent of induced pluripotent stem cell (iPSC) technology a
      decade ago, enormous progress has been made in stem cell biology and regenerative
      medicine. Human iPSCs have been widely used for disease modeling, drug discovery,
      and cell therapy development. In this review, we discuss the progress in
      applications of iPSC technology that are particularly relevant to drug discovery
      and regenerative medicine, and consider the remaining challenges and the emerging
      opportunities in the field. Data Sources: Articles in this review were searched
      from PubMed database from January 2014 to December 2017. Study Selection:
      Original articles about iPSCs and cardiovascular diseases were included and
      analyzed. Results: iPSC holds great promises for human disease modeling, drug
      discovery, and stem cell-based therapy, and this potential is only beginning to
      be realized. However, several important issues remain to be addressed.
      Conclusions: The recent availability of human cardiomyocytes derived from iPSCs
      opens new opportunities to build in vitro models of cardiac disease, screening
      for new drugs and patient-specific cardiac therapy.

PMID- 29578132
TI  - Study Progress of the Influence of Atrial Fibrillation Treatment on Dementia.

PMID- 29578134
TI  - Imaging Features of Uterine Leiomyomatosis with the Inferior Vena Cava and the
      Right Atrium Involvement.

PMID- 29578133
TI  - Liquid Chromatography-Tandem Mass Spectrometry-Based Characterization of Steroid
      Hormone Profiles in Healthy 6 to 14-Year-Old Male Children.

PMID- 29578135
TI  - Accessory Spleen Presenting as a Submucosal Lesion on Stomach Wall after
      Splenectomy.

PMID- 29578136
TI  - A New Technique for Identifying the Recurrent Laryngeal Nerve: Our Experience in
      71 Patients.

PMID- 29578137
TI  - Bilateral Lower Limb and Abdominal Elephantiasis Due to Erysipelas.

PMID- 29578138
TI  - Laparoscopic Retrieval of a Tilted Inferior Vena Cava Filter.

PMID- 29578139
TI  - Multibacillary Leprosy in a Child.

PMID- 29578141
TI  - Interesting dynamic contrast-enhanced magnetic resonance imaging findings of
      metaplastic breast carcinoma with skeletal muscle metastasis.

PMID- 29578140
TI  - Specific White Matter Impairments in Patients with Treatment-Refractory First
      Episode Schizophrenia: A 1-Year Follow-up Pilot Study.

PMID- 29578142
TI  - Learning from Clostridium novyi-NT: How to defeat cancer.
AB  - Side effects associated with conventional anticancer therapies have prompted the
      new idea of solid tumor treatment strategy. One of them is using bacteria
      explored as potential antitumor agents over more than one century. Notably, the
      ideal therapy is a specifical target to tumors with limited toxicity. Here, we
      take "Clostridium novyi" for the search keyword in the PubMed from 2000 to 2015
      and describe that C. novyi-NT spores act as "Trojan horse" for bacteriolytic
      therapy. This therapy is based on the fact that the live and attenuated obligate
      anaerobic bacteria are capable of binary fission selectively in anoxic areas of
      solid tumors and direct tumoricidal effects. Our succinct review mainly
      concentrates on the potential mechanisms of combination bacteriolytic therapy, an
      effective and safe tumor therapy with the help of C. novyi-NT. Importantly, C.
      novyi-NT spores were shown to induce solid tumor regression and exhibit the
      property to initiate an immune response. Therefore, C. novyi-NT spores should be
      an effective and safe tumor therapy.

PMID- 29578143
TI  - The relationship of indoor coal use and environmental tobacco smoke exposure with
      lung cancer in China: A meta-analysis.
AB  - Objective: To assess the association between long-term exposures to smoky coal,
      environmental tobacco smoke (ETS) and lung cancer incidence in China. Methods: A
      meta-analysis was performed on literature searched through Web of Science,
      Chinese National Knowledge Infrastructure, Weipu, and Wanfang databases. Odds
      ratio (OR) with 95% confidence intervals (CIs) was used to assess the strength of
      association between air pollution and lung cancer in China. Results: Twenty-eight
      studies were included in the meta-analysis. Stratification by ETS exposure
      source, amount, and gender found a variation in effect. The pooled OR (95% CI)
      for exposure to spousal, parents, and work ETS was 1.153 (1.000-1.329), 2.117
      (1.626-2.755), and 1.454 (1.307-1.618), respectively. The OR (95% CI) values
      related to childhood exposure was 1.297 (1.142-1.473), adulthood exposure 1.102
      (0.937-1.296), exposure lower than 20 cigarette/day 1.088 (0.809-1.464), higher
      than 20 cigarette/day 1.776 (1.392-2.267), male 1.555 (1.304-1.855), female 1.487
      (1.265-1.748), and coal use 1.490 (1.330-1.669). Conclusion: The meta-analysis
      provided evidence that indoor coal use and ETS were significantly associated with
      lung cancer in China.

PMID- 29578144
TI  - Transdermal fentanyl for cancer pain: Trial sequential analysis of 3406 patients
      from 35 randomized controlled trials.
AB  - Objective: The aim of this study was to assess the effectiveness and safety of
      transdermal fentanyl for the treatment of moderate or severe cancer-related pain.
      Materials and Methods: Electronic databases including PubMed, Embase, the
      Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, the
      Chinese Biomedical Literature Database, and Chongqing Weipu and Wanfang Database
      were searched for relevant studies published prior to January 2015. Only
      randomized controlled trials on the use of the transdermal fentanyl patch for the
      treatment of cancer pain were selected. Two reviewers independently screened the
      studies and extracted data. The quality assessment of the studies included was
      based on the Cochrane Handbook for Systematic Reviews of Interventions (version
      5.1.0). RevMan 5 (version 5.3) and Trial Sequential Analysis software (TSA,
      version 2.1, provided by Copenhagen Trial Unit, Denmark) were used for data
      analyses. Results: A total of 35 studies involving 3406 participants met the
      inclusion criteria for this meta-analysis. There was no statistically significant
      difference with regard to the effectiveness of management for cancer pain between
      the use of transdermal fentanyl patch and oral morphine (risk ratio = 1.00, 95%
      confidence interval, 0.97-1.03, P > 0.05). TSA results demonstrated that the
      cumulative Z-score crossed its monitoring boundaries, and therefore, reliable
      conclusions had been drawn. Moreover compared with oral morphine, the use of
      transdermal fentanyl patch resulted in statistically significantly decreased
      incidence of constipation, nausea and vomiting, drowsiness, and urinary
      retention. There was a significantly greater incidence of skin irritation in
      patients who used a transdermal fentanyl patch (P < 0.05). Conclusions: The
      findings from this study demonstrate that use of transdermal fentanyl for the
      management of moderate or severe cancer pain had more advantages compared to oral
      morphine.

PMID- 29578145
TI  - Identifying key genes in retinoblastoma by comparing classifications of several
      kinds of significant genes.
AB  - Objective: The objective of this paper was to investigate key genes in
      retinoblastoma using a novel method which is mainly based on five kinds of genes,
      differentially expressed genes (DEGs), differential pathway genes (DPGs), seed
      genes (common genes between DEGs and DPGs), hub genes and informative genes
      (common genes of hub genes and DEGs), and support vector machines (SVM) model.
      Materials and Methods: In the proposed method, the first step was to identify
      five types of significant genes. DEGs were identified using linear models for
      microarray data (Limma) package (The Walter and Eliza Hall Institute of Medical
      Research, Melbourne, Australia). DPGs were originated from differential pathways
      based on attract method. Hub genes of mutual information network which is
      constructed by the context likelihood of relatedness algorithm were obtained
      according to topological degree centrality analysis. For the second step, SVM
      model was implemented to assess the classification performance of DEGs, DPGs,
      seed genes, hub genes, and informative genes, depending on its induces the area
      under the receiver operating characteristics curve (AUC), true negative rate
      (TNR), true positive rate (TPR) and the Matthews coefficient correlation
      classification (MCC). Results: We detected 479 DEGs, 747 DPGs, 29 seed genes, 34
      hub genes, and 7 informative genes in total for retinoblastoma. The
      classification performance of informative genes was the best of all with AUC =
      1.00, TNR = 1.00, TPR = 1.00, and MCC = 1.00, hence they were considered to key
      genes which included EPARS1, FN1, HLA-DPA1, HLA-DPB1, HLA-DRA, CFI, and
      transforming growth factor, beta receptor II. Conclusions: We have successfully
      identified seven key genes, which might be potential biomarkers for detection and
      therapy of retinoblastoma for current and future study.

PMID- 29578146
TI  - Human epidermal growth factor receptor 2, epidermal growth factor receptor, and c
      MET overexpression and survival in biliary tract cancer: A meta-analysis.
AB  - Background: Tyrosine kinase growth factor receptors (TKGFRs) play an important
      role in the progression of cancer. A variety of studies have investigated the
      clinicopathologic correlation of these receptors and their influences on patient
      survival in different types of cancer. As the members of TKGFRs, the biomarkers c
      MET, epidermal growth factor receptor (EGFR), and human epidermal growth factor
      receptor 2 (HER-2) have been extensively investigated in biliary tract cancer
      (BTC). However, their prognostic value is still controversial. Our study aimed to
      evaluate the prognostic significance of the three markers in BTC patients based
      on the published studies. The correlation between high expression of these
      markers and clinical parameters or overall survival (OS) has been assumed in this
      paper. Materials and Methods: Including PubMed, EMBASE, China National Knowledge
      Infrastructure, and Springer, a comprehensive search for the related literature
      published in Chinese and English has been done. Finally, 31 studies were selected
      in our research. Results: Surprisingly, the meta-analysis indicated that HER-2
      high expression was not correlated with age, gender, primary tumor, tumor node
      metastasis (TNM) stage, lymph node status, and differentiation. We also found
      that EGFR high expression was not associated with the parameters, such as age,
      gender, TNM stage, differentiation, or lymph node status. c-MET high-expression
      was not associated with age, differentiation, gender, TNM stage, or lymph node
      status. In addition, our study showed that HER-2, EGFR, and c-MET high expression
      had an adverse influence on OS in BTC, the pooled hazard ratio for HER-2, EGFR,
      and c-MET was statistically significant. Conclusion: The present meta-analysis
      indicated that EGFR and HER-2 high expression have little impact on OS in
      patients with BTC while c-MET high expression influenced OS in patients with BTC
      to a large extent. However, c-MET, EGFR, and HER-2 expression did not show any
      correlation with those clinical parameters. c-MET may be a potential therapeutic
      target for BTC.

PMID- 29578147
TI  - Comparison of the efficacy of strontium-89 chloride in treating bone metastasis
      of lung, breast, and prostate cancers.
AB  - Objective: The aim of this study was to comparatively evaluate the efficacy of
      strontium-89 chloride (89 SrCl2) in treating bone metastasis-associated pain in
      patients with lung, breast, or prostate cancer. Materials and Methods: The 126
      patients with lung cancer included 88, 16, 15, 4, and 3 patients with
      adenocarcinoma, squamous cell carcinoma, nonsmall cell carcinoma, mixed
      carcinoma, and small cell carcinoma, respectively, and the control group
      consisted of patients with breast (71 patients) or prostate cancer (49 patients)
      who underwent 89 SrCl2 treatment during the same period. The treatment dose of 89
      SrCl2 was 2.22 MBq/kg. Results: The efficacy rate of treatment in the lung cancer
      group was 75.4%, compared to 95.0% in the control group. Approximately 67% of
      patients with lung cancer and bone metastases and 47% of control patients
      exhibited mild-to-moderate reductions of leukocyte and platelet counts 4 weeks
      after 89 SrCl2 treatment. Conclusions: 89 SrCl2 can safely and effectively
      relieve bone pain caused by bone metastasis from lung cancer. However, its
      efficacy was lower in patients with lung cancer with bone metastasis than in
      those with breast or prostate cancer with bone metastasis, and its effects on the
      peripheral hemogram were also significantly stronger in the lung cancer group.

PMID- 29578148
TI  - Effect of inhibition of intermediate-conductance-Ca2+-activated K+ channels on
      HeLa cell proliferation.
AB  - Purpose: To explore the influence of intermediate-conductance-Ca2+-activated K+
      channels. (IKCal) on HeLa cell proliferation. Materials and Methods: An IKCal
      blocking agent (clotrimazole (CLT)) and small hairpin ribonucleic acid
      interference (RNAi) was used to block IKCal in HeLa cells; subsequently, cell
      growth was observed. Furthermore, the messenger ribonucleic acid (mRNA)
      expression of IKCal was detected by reverse transcriptase polymerase chain
      reaction (RT-PCR) after IKCal-blocking. Results: The obvious morphological
      changes in HeLa cells were observed 48 h after CLT-blocking. The PCR results
      indicated that CLT reduced the mRNA expression of IKCal in HeLa cells. HeLa cells
      were transfected with pGenesil via RNAi; the HeLa cells transfected with pGenesil
      IK displayed obvious morphological changes 48 h after transfection. In addition,
      RT-PCR further demonstrated the reduced mRNA expression of IKCal in the pGenesil
      group. Conclusion: CLT and blocking of IKCal gene expression effectively inhibits
      HeLa cell proliferation; therefore, the use of a blocking agent and RNAi both
      effectively downregulated the mRNA expression of IKCal, which in turn mediated
      the proliferation of HeLa cells, producing an antitumor effect.

PMID- 29578149
TI  - Hypoxia-inducible factor-1alpha rs11549465 C>T and rs11549467 G>A gene
      polymorphisms are associated with an increased risk of digestive cancers in
      Asians.
AB  - Objective: We used a meta-analysis framework to examine the correlation between
      HIF-1alpha gene polymorphisms and the susceptibility to digestive cancers.
      Methods: Cochrane Library Database, EMBASE, MEDLINE, Pubmed, CINAHL, Chinese
      Biomedical Database and Web of Science were searched without language
      restrictions to identify relevant case-control studies reporting data on HIF
      1alpha gene polymorphisms in digestive cancers. Data was extracted from the
      selected studies and meta-analysis was carried out using STATA 12.0 and
      Comprehensive Meta-analysis 2.0 softwares. Relative risk (RR) and its 95%
      confidence interval (95%CI) were calculated. A total of 8 eligible case-control
      studies were included. These 8 studies contained a combined total of 1,276
      patients diagnosed with various digestive cancers and 3,392 healthy controls. Two
      functional HIF-1alpha polymorphisms (rs11549465 C>T and rs11549467 G>A) were
      examined in these 8 studies. Results: Our findings demonstrated that both
      rs11549465 C>T and rs11549467 G>A HIF-1alpha polymorphisms conferred
      significantly increased risk of digestive cancers. However, ethnicity-stratified
      analysis revealed that HIF-1alpha rs11549465 C>T and rs11549467 G>A polymorphisms
      were associated with an elevated risk of digestive cancer in Asians, but not in
      Caucasians. These two polymorphisms also conferred different degrees of
      susceptibility to various digestive cancer types. Conclusion: Our meta-analysis
      suggests that HIF-1alpha rs11549465 C>T and rs11549467 G>A polymorphisms
      influence the pathogenesis of digestive cancers in Asians.

PMID- 29578150
TI  - Elevated expression of matrix metalloproteinase-9 is associated with bladder
      cancer pathogenesis.
AB  - Objective: This study investigated the association between abnormal matrix
      metalloproteinase-9 (MMP-9) expression and bladder cancer (BC) development.
      Materials and Methods: In a retrospective analysis, this study used tissue
      samples derived from 92 patients pathologically diagnosed with BC (experimental
      group), who were hospitalized between September 2012 and June 2014 at the Urinary
      Surgery of Department of Urology, Lanzhou University Second Hospital. As controls
      (control group), 63 normal pericancerous bladder mucosal tissues (3 cm distant
      form edge of BC foci) with confirmed pathology were selected from the same time
      period. Immunohistochemistry was employed to detect MMP-9 protein expression in
      the tissues and enzyme-linked immunosorbent assay was performed to measure MMP-9
      protein levels in tissue samples of patients and control subjects. Finally, a
      meta-analysis was conducted to understand the overall impact of MMP-9 on BC
      pathogenesis. STATA 12.0 software (Stata Corp, College Station, TX, USA) was used
      for all statistical analyses. Results: The MMP-9 positive expression rate in
      tissue samples and MMP-9 levels were significantly greater in the experimental
      group compared to the control group (both P < 0.001). The frequency of MMP-9
      positive status showed statistically significant differences between G1 (low
      grade) and G3 (high-grade) (P < 0.001), between G2 and G3 (P < 0.05), and between
      G1/G2 and G3 (P = 0.001). Our meta-analysis findings provided further evidence
      that MMP-9 positive expression status and MMP-9 levels in the experimental group
      were significantly higher than the control group (positive expressions: Odds
      ratio [OR] = 18.59, 95% confidence interval [95% CI] = 11.63-29.71, P < 0.001;
      expression levels: Standard mean difference = 1.51, 95%CI = 0.63-2.39, P =
      0.001). The positive expression status of MMP-9 was notably lower in G1/G2
      compared to G3 (OR = 0.24, 95%CI = 0.15-0.36, P < 0.001). Conclusion: Our study
      demonstrated that both positive expression status in tumor tissue and expression
      levels of MMP-9 are significantly elevated in BC patients and correlate with
      disease progression. Thus, MMP-9 can serve as a biomarker to determine the degree
      of BC malignancy.

PMID- 29578151
TI  - MiR-186 inhibits cell proliferation and invasion in human cutaneous malignant
      melanoma.
AB  - Aims: MicroRNA-186 (miR-186) has been shown to be involved in various types of
      cancer. The purpose of this study was to investigate the expression level and
      functional role of miR-186 in human cutaneous malignant melanoma cells. Subjects
      and Methods: Expression of miR-186 was analyzed in human cutaneous malignant
      melanoma (CMM) cell lines SK-MEL-1, G-361, A375 and A875, and human normal
      epidermal melanocytes cell line HEMn-LP by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). Additionally, the functional role of miR-186
      on melanoma cells was investigated by transfection of miR-186 mimic followed by
      analyses of cell proliferation, apoptosis, and metastasis. Results: We found that
      the expression levels of miR-186 were decreased in CMM cell lines compared with
      normal epidermal melanocytes cell line. Moreover, overexpression of miR-186
      inhibited cells proliferation through abrogating the G1-S transition, and reduced
      cells migration and invasion. Conclusions: Our findings suggested that miR-186
      exhibit an inhibitory effect on CMM cell proliferation, migration, and invasion;
      thus, may serve as a potential therapeutic target for human CMM intervention.

PMID- 29578152
TI  - Death-associated protein kinase promoter methylation correlates with
      clinicopathological and prognostic features in nonsmall cell lung cancer
      patients: A cohort study.
AB  - Objective: The objective was to study the correlation between death-associated
      protein kinase (DAPK) promoter methylation and the clinicopathological and
      prognostic features in nonsmall cell lung cancer (NSCLC) patients. Materials and
      Methods: A total of 117 NSCLC patients were recruited into our study between
      December 2012 and December 2014. Methylation-specific polymerase chain reaction
      was employed to detect the methylation status of DAPK in cancer tissues,
      peficancerous tissues, and serum samples of 117 NSCLC patients. In addition,
      serum samples of 115 healthy subjects were analyzed as controls. A literature
      search of English and Chinese databases, based on predefined criteria, identified
      published studies closely related to this study. Data were extracted, and meta
      analysis was performed using STATA 12.0 software (STATA Corporation, College
      Station, TX, USA). Results: Our study results showed that DAPK promoter
      methylation frequency was significantly higher in NSCLC tissues compared to
      peficancerous normal tissues (58.1% vs. 12.8%, chi2 = 52.45, P < 0.001). When
      serum samples were compared, DAPK methylation frequency in NSCLC patients was
      higher than the control group (27.4% vs. 0, chi2 = 37.07, P < 0.001). Our meta
      analysis results demonstrated that DAPK methylation frequency was lower in tumor
      node metastasis (TNM) stage I-II compared to TNM stage III-IV (relative risk [RR]
      =0.87, 95% confidence interval [CI] =0.76-0.99, P = 0.041). DAPK promoter
      methylation frequency in NSCLC patients with lymph node metastasis was
      significantly higher compared to the patients with no metastases (RR = 1.26, 95%
      CI = 1.04-1.52, P = 0.020). Finally, the 5-year survival rate was lower in NSCLC
      patient group with high frequency of DAPK methylation, compared to the patient
      group with unmethylated DAPK (RR = 0.71, 95% CI = 0.56-0.89, P = 0.004).
      Conclusion: Our results showed that DAPK promoter methylation is tightly
      correlated with clinicopathological features of NSCLC and is associated with poor
      prognosis in patients.

PMID- 29578153
TI  - Dual-specificity phosphatase 6 genetic variants associated with risk of lung
      squamous cell carcinoma in Han Chinese.
AB  - Background: Nonsmall cell lung cancer (NSCLC) mainly contains adenocarcinoma (AC)
      and squamous cell carcinoma (SqCC). This study investigated single nucleotide
      polymorphism (SNP) of topoisomerase II alpha (TOP2A) and dual-specificity
      phosphatase 6 (DUSP6) in a hospital-based case and control cohort of individuals
      for association with risk of different histological subtypes of NSCLC. Materials
      and Methods: A total of 454 (237 SqCC and 217 AC) NSCLC patients, and 454 healthy
      controls were recruited for analysis of TOP2A rs471692 and DUSP6 rs2279574
      genotypes using the TaqMan polymerase chain reaction technique. Results: TOP2A
      rs471692 and DUSP6 rs2279574 SNPs were in complete linkage disequilibrium;
      however, frequency of DUSP6 rs2279574 genotype was significantly different
      between the case and control, that is, DUSP6 rs2279574a/A and A/C genotypes might
      contribute to an increased risk of lung squamous carcinoma compared with the C/C
      genotype. Moreover, DUSP6 rs2279574 AA genotype was also significantly associated
      with advanced stages of lung cancer. In contrast, frequency of the TOP2A rs471692
      genotype had no association between cases and controls (P = 0.906). Genotype
      frequency of DUSP6 rs2279574 was 11.9% for C/C, 43.6% for C/A, and 44.5% for A/A
      in the case versus 16.7% C/C, 43.4% C/A, and 39.9% A/A in the control population
      (chi2 = 3.136, P= 0.077 by Hardy-Weinberg equilibrium test [HWE]). The genotype
      frequency of TOP2A rs471692 was 50.0% for C/C, 41.6% for C/T, and 8.4% for T/T in
      the case versus 50.2% C/C, 43.0% C/T, and 6.8% T/T in the control populations
      (chi2 = 0.023, P= 0.879 by HWE test). Conclusion: Individuals are carrying DUSP6
      rs2279574 AA and AC genotypes associated with an increased risk in developing
      lung squamous carcinoma in Han Chinese and with advanced NSCLC stages.

PMID- 29578154
TI  - Meta-analysis of molecular targeted agents in the treatment of elderly patients
      with metastatic colorectal cancer: Does the age matter?
AB  - Aim: Patients aged 65 years and older are often underrepresented in clinical
      trials of metastatic colorectal cancer (mCRC) and probably undertreated in
      clinical practice. We performed a meta-analysis of randomized controlled trials
      (RCTs) to assess the efficacy of molecular targeted agents (MTAs) in this
      population. Materials and Methods: A comprehensive literature search for studies
      published up to December 2014 was performed. The endpoints were overall survival
      (OS) and progression-free survival (PFS). The pooled hazard ratio (HR) and 95%
      confidence intervals (CIs) were calculated employing fixed- or random-effects
      models depending on the heterogeneity of the included trials. Results: Eleven
      RCTs involving 8,488 patients were ultimately identified. The pooled analysis
      demonstrated that the use of MTAs in elderly patients with mCRC significantly
      improve OS (HR 0.84, 95% CI: 0.76-0.92, P < 0.001) and PFS (HR 0.78, 95% CI: 0.64
      0.96, P = 0.017) when compared to MTAs-free therapies. Similar results of OS were
      observed in subgroup analysis according to treatment line, therapy regimes, and
      approval status of MTAs. No publication bias was detected by Begg's and Egger's
      tests. Conclusions: The introduction of MTAs to therapies offered a survival
      benefit in elderly patients with mCRC. Further studies aimed at this specific
      patient population were still needed to watchfully monitor potential treatment
      related toxicities to optimize the use of these drugs.

PMID- 29578155
TI  - Meta-analysis of prognostic value of inflammation parameter in breast cancer.
AB  - Context: Recently, increasing studies investigated the association between
      inflammation parameter such as neutrophil to lymphocyte ratio (NLR) and the
      prognosis of cancers. However, the clinical and prognostic significance of NLR in
      breast cancer remains controversial. Aim: This meta-analysis was conducted to
      establish the overall accuracy of the NLR test in the diagnosis of breast cancer.
      Materials and Methods: A comprehensive search of the literature was conducted
      using PubMed and Web of Science. Six studies dating up to July 2014 with 2267
      patients were enrolled in the present study. STATA 11.0 software (STATA
      Corporation, College Station, TX, USA) was selected for data analysis. In order
      to evaluate the association between NLR and overall survival (OS), disease-free
      survival (DFS), recurrence-free survival or cancer-specific survival, the hazard
      ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Results:
      Subgroup analyses showed that NLR was a strong prognostic factor for OS in
      multivariate analysis (HR = 2.81, 95% CI = 2.13-3.71, PH = 0.992) and without
      metastasis (HR = 1.45, 95% CI = 0.37-5.66, PH < 0.001). Elevated NLR was
      associated with a high risk for DFS in subgroups of multivariate analysis (HR =
      2.16, 95% CI = 1.67-2.80, PH = 0.977) and mixed metastasis (HR = 2.13, 95% CI =
      1.38-3.30, PH = 0.84). Conclusion: In summary, NLR may be considered as a
      predictive factor for patients with breast cancer.

PMID- 29578156
TI  - Circulating gelatinases are not prognostic of treatment response and survival in
      locally advanced rectal cancer patients undergoing preoperative
      chemoradiotherapy.
AB  - Purpose: To investigate whether the serum levels of matrix metalloproteinases
      (MMPs) are predictive on treatment response and survival in locally advanced
      rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy. Patients
      and Methods: Serum MMP-2 and MMP-9 was analyzed by enzyme-linked immunosorbent
      assay and obtained before, midway, and 1-month after the end of preoperative
      radiotherapy treatment. The prognostic significance of serum MMP-2 and MMP-9
      levels and their association with other pathological findings for LARC patients
      were evaluated. Results: Serum levels of MMP-2 or MMP-9 were found to decrease
      with increasing clinical stage and negative correlation was statistically
      significant (P < 0.05). There was no statistically significant difference in
      tumor response and survival between the low and high MMP-2 and MMP-9 groups. MMP
      2 and MMP-9 were not correlated with local-regional recurrence. Conclusions: We
      propose that serum levels of MMP-2 and MMP-9 are not predictive on treatment
      response and survival in LARC patients.

PMID- 29578157
TI  - miR-146a rs2910164 polymorphism and the risk of colorectal cancer in Chinese
      population.
AB  - Objective: MicroRNAs-associated single nucleotide polymorphisms are thought to
      play an important role in cancer development. We investigated the association of
      miR-146a rs2910164 polymorphism with the risk of colorectal cancer (CRC) in
      Chinese population. Materials and Methods: In this hospital-based case-control
      study of 560 cases and 780 age- and gender-matched healthy controls, the miR-146a
      rs2910164 polymorphism was genotyped by polymerase chain reaction-restriction
      fragment length polymorphism. Results: We found that miR-146a rs2910164
      polymorphism was not associated with CRC risk. However, the subgroup analysis by
      gender showed significant associations in male subjects (GG vs. CC: Odds ratios
      [OR] = 1.54, 95% confidence intervals [CI] = 1.04-2.29, P = 0.03; G vs. C: OR =
      1.21, 95% CI = 1.01-1.45, P = 0.04). Conclusion: Our study provides evidence that
      miR-146a rs2910164 polymorphism may play an important role in susceptibility to
      CRC in Chinese male population.

PMID- 29578158
TI  - Effect of spleen tyrosine kinase on nonsmall cell lung cancer.
AB  - Aim of Study: To investigate the anti.tumor effect of spleen tyrosine kinase.
      (Syk) on the human nonsmall cell lung cancer cells in vitro and its mechanism.
      Materials and Methods: In this study, we constructed a eukaryotic expression
      vector pcDNA3.1D/V5-His-TOPO/Syk and transfected it into human nonsmall cell lung
      cancer cells A549. Then, we not only analyzed the expression of Syk in
      transfected cells and its invasion but also the expression of matrix
      metalloproteinase-9 (MMP-9). Results: The results showed that overexpressed Syk
      significantly inhibited A549 cell invasive ability by decreasing the expression
      of MMP-9. Conclusion: The overexpressed Syk plays an important role in tumor
      invasion and metastasis, and a negative role in human nonsmall cell lung cancer
      cells.

PMID- 29578159
TI  - Cyclooxygenase-2 gene polymorphisms and susceptibility to hepatocellular
      carcinoma: A meta-analysis based on 10 case-control studies.
AB  - Objective: The association between cyclooxygenase-2 (COX-2) gene polymorphisms
      and hepatocellular carcinoma (HCC) has been widely reported, but the results are
      still controversial. To clarify the effect of COX-2 -1195G/A (rs689466), -765G/C
      (rs20417), and +8473T/C (rs5275) polymorphisms on HCC risk, a meta-analysis was
      performed. Materials and Methods: The PubMed, Embase, Cochrane Library, Web of
      Science, Chinese BioMedical Literature, Wanfang, and Chinese National Knowledge
      Infrastructure databases were systematically searched to identify potential
      studies published up to October 10, 2014. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated to assess the strength of association. A total of
      eight studies with 2060 HCC cases and 2610 controls for -1195G/A, six studies
      with 1295 cases and 2193 controls for -765G/C, and four studies with 1477 cases
      and 1747 controls for +8473T/C were included in this meta-analysis. Results:
      Overall, the COX-2 -1195G/A, and +8473T/C polymorphisms were both significantly
      associated with an increased risk of HCC (rs689466 GA + AA vs. GG: OR = 1.390, P
      = 0.006, 95% CI: 1.099-1.759, I2 = 50.7%, Pheterogeneity = 0.048; rs5275 CC vs.
      TT + TC: OR = 1.484, P = 0.041, 95% CI: 1.017-2.165, I2 = 0.0%, Pheterogeneity =
      0.416). In the subgroup analyses stratified by ethnicity, the COX-2 -1195G/A, 
      765G/C, and +8473T/C were all associated with an increased HCC risk in Asian
      populations (rs689466 A vs. G: OR = 1.346, P = 0.001, 95% CI: 1.137-1.595, I2 =
      0.0%, Pheterogeneity = 0.869; rs20417 CC vs. GG + GC: OR = 3.069, P = 0.013, 95%
      CI: 1.265-7.447; rs5275 CC vs. TT + TC: OR = 1.626, P = 0.020, 95% CI: 1.079
      2.452, I2 = 0.0%, Pheterogeneity = 0.495). Conclusions: Our meta-analysis
      suggests that -1195G/A, -765G/C, and +8473T/C in COX-2 may contribute
      significantly to HCC risk.

PMID- 29578160
TI  - Concomitant high expression of survivin and vascular endothelial growth factor-C
      is strongly associated with metastatic status of lymph nodes in papillary thyroid
      carcinoma.
AB  - Purpose: Papillary thyroid carcinoma (PTC) has a strong propensity to metastasize
      to regional lymph nodes which increases the risk of local-regional relapse and
      affects the course of the disease. Molecular pathogenesis of lymph node
      metastasis (LNM) is not yet fully understood. Survivin, a multifunctionale
      molecule involved in apoptosis, proliferation and angiogenesis, and vascular
      endothelial growth factor-C (VEGF-C) are suggested to be implicated in lymphatic
      metastases of human malignancies. Materials and Methods: Expression of survivin
      and VEGF-C was examined by immunohistochemistry and Western blot in 75 cases of
      PTCs in relation to their LNM status. Additionally, survivin and VEGF-C were
      immunohistochemically analyzed in 15 primary PTCs paired with their metastatic
      tissue in lymph nodes. Results: High expression of survivin and VEGF-C was found
      in 62.7% and 64.0% cases, respectively, with a positive correlation to each other
      (Spearman's correlation co-efficient = 0.878, P < 0.001). Expression levels of
      both proteins were significantly higher in patients with LNM than in those
      without LNM (P < 0.001). The rate of concomitant high expression of survivin and
      VEGF-C in patients with LNM involvement was 88.9% (P < 0.01). Metastatic tissue
      in lymph nodes expressed survivin and VEGF-C at the same high extent as their
      primary tumors. Conclusion: Concomitant high expression of survivin and VEGF-C is
      closely associated with LNM status of PTC patients, which suggests their
      cooperation in the metastatic process. Evaluation of survivin and VEGF-C
      expression could be clinically significant in predicting the metastatic potential
      of PTC and subsequent treatment and follow-up of these patients.

PMID- 29578161
TI  - Incidence of radiation enteritis in cervical cancer patients treated with
      definitive radiotherapy versus adjuvant radiotherapy.
AB  - Objective: The study aimed to evaluate the incidence of early and late radiation
      enteritis in cervical cancer patients receiving definitive or adjuvant
      radiotherapy (RT). Materials and Methods: Three hundred and twenty-four cervical
      cancer patients receiving definite or adjuvant RT in our hospital from January
      2010 to December 2012 were divided into definitive (132 patients) or adjuvant RT
      (192 patients) and performed detailed analysis. Results: Early radiation
      enteritis was found in 54.3%, and late radiation enteritis was found in 17.9% of
      cervical patients. Early (P < 0.007) and late (P < 0.003) radiation enteritis
      appeared more frequently in patients treated with definitive RT than that with
      adjuvant RT. In the definitive RT group, incidence of both early and late
      radiation enteritis in the RT group was higher than in the radiochemotherapy
      (RCHT) group, and the difference was statistically significant (P < 0.004).
      Severe cases of late radiation enteritis (Grade 3 and 4) can be seen higher in
      the definitive radiation group (both the RT and RCHT group) than in the adjuvant
      radiation group, and the difference was statistically significant (P < 0.005).
      Conclusion: The incidence of both early and late radiation enteritis in the
      definitive RT group is higher than in the adjuvant RT group. The occurrence of
      side effects was associated with the prolongation of total irradiation time due
      to necessary interruptions of RT. Methods to decrease the interruptions in the RT
      and the irradiated volume of the small bowel will further lessen enteric
      morbidity.

PMID- 29578162
TI  - The autophagy induced by curcumin via MEK/ERK pathway plays an early anti
      leukemia role in human Philadelphia chromosome-positive acute lymphoblastic
      leukemia SUP-B15 cells.
AB  - Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +
      ALL) is triggered by BCR/ABL tyrosine kinase which activates the downstream
      signaling pathways, such as Akt/mTOR, RAF/MEK/ERK, and STAT5 pathways. Curcumin
      has been shown to have inhibitory effects on cancers by inducing apoptosis and
      autophagy. We demonstrated that curcumin inhibited activation of Akt-mTOR,
      ABL/STAT5 pathways, inhibited cell proliferation, and induced apoptosis in Ph +
      ALL cells. Experiments here, were conducted to determine whether autophagy via
      MEK/ERK pathway involved in anti-leukemia effect of curcumin in Ph + ALL.
      Materials and Methods: Ph + ALL cell line SUP-B15 was treated with curcumin.
      Cytotoxic activity of curcumin was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl-2H-tetrazolium bromide assay. Signaling protein and specific maker of
      autophagy and conversion of LC3-I to LC3-II were determined by Western blot
      analysis. Cell apoptosis was determined by flow cytometry. Results: Curcumin
      treatment up-regulated the activation of RAF/MEK/ERK at 4 h and 8 h after
      curcumin exposure in SUP-B15 cells, curcumin treatment induced autophagy at
      exactly 4 h and 8 h after curcumin exposure. Curcumin exerted cytotoxic activity
      against SUP-B15 cells at 4 h and 8 h, which was independent of apoptosis. MEK
      specific inhibitor U0126 inhibited the occurrence of autophagy, and then blocked
      curcumin-induced cytotoxicity at 4 h and 8 h. Conclusions: Curcumin induce
      autophagic cell death in SUP-B15 cells via activating RAF/MEK/ERK pathway. These
      findings suggest that autophagic mechanism contribute to the curcumin-induced
      early SUP-B15 cell death, and autophagy is another anti-leukemia mechanism of
      curcumin.

PMID- 29578163
TI  - Upregulation of miR-371-373 cluster, a human embryonic stem cell specific
      microRNA cluster, in esophageal squamous cell carcinoma.
AB  - Aims: Esophageal squamous cell carcinoma (ESCC) is the most common subtype of
      esophageal cancer in Iran. MicroRNAs (miRNAs) are a class of noncoding RNAs that
      are found to be involved in different processes and can play a role in
      tumorigenesis and result in cancer. MiR-371, miR-372, and miR-373 are a gene
      cluster that is located in the region of the human chromosome of 19q13.4. They
      are specifically expressed in human embryonic stem cells (ESCs) and involved in
      the maintenance of the stemness features through regulating the expression of
      certain key genes and signaling pathways. The present study investigated the
      potential expression of miR-371-373 cluster in tumor and nontumor tissues of
      ESCC. Materials and Methods: The expression level of miR-371-373 cluster was
      analyzed in paraffin-embedded tissues of tumor and tumor margin in 36 patients
      with ESCC. Total RNA was isolated and the miR-371-373 clusters were quantified
      with quantitative real-time-polymerase chain reaction expression analysis.
      Computed tomography analysis (2-DeltaDeltaCT) and t-test were used to determine
      the relationship between the characteristics of the tumor and nontumor tissues.
      Statistically, P value of <0.05 were considered significant. Data analysis was
      performed using SPSS 16. Results: We provided miR-371, miR-372, and miR-373
      upregulation evidence significantly with 14.36, 26.9, and 21.1-fold in esophageal
      cancer cells compared with their adjacent normal cells (P < 0.05), respectively.
      In addition, evaluation of these genes expression in various grades didn't show a
      significant difference. Conclusion: Our findings support the hypothesis that
      these miRNAs might play a role in tumorigenesis in esophageal cancer.

PMID- 29578164
TI  - Phosphatase and tensin homolog protein may be linked to lymph node metastasis and
      tumor node metastasis staging in nonsmall cell lung cancer.
AB  - Background: This study aims to investigate the correlations of positive rate of
      phosphatase and tensin homolog (PTEN) protein with lymph node metastasis (LNM)
      and tumor node metastasis (TNM) staging of nonsmall cell lung cancer (NSCLC)
      patients by conducted a meta-analysis. Materials and Methods: Covering several
      electronic databases (Embase, Cochrane Library, China BioMedicine, China National
      Knowledge Infrastructure, PubMed, and Web of Science), published papers eligible
      for enrollment in the current meta-analysis had to fulfill our predefined
      selection criteria. Odds ratios (ORs) with their 95% confidence interval (95%CI)
      were aggregated utilizing comprehensive meta-analysis 2.0 software (Biostatic
      Inc., Englewood, New Jersey, USA). Results: Twelve cohort studies with a total of
      419 NSCLC patients were incorporated into the current meta-analysis. A decreased
      positive rate of PTEN protein was detected in NSCLC patients with TNM stage III
      IV rather than those patients with TNM stage I-II (OR = 0.454, 95%CI = 0.338
      0.610, P < 0.001). PTEN in NSCLC patients without LNM expressed higher than that
      in the patients with LNM (OR = 0.532, 95%CI: 0.299-0.948, P = 0.032). Ethnicity
      stratified analysis demonstrated a negative relationship between positive rate of
      PTEN protein and TNM staging of NSCLC among both Asians and Caucasians (both P <
      0.05). However, we found no significant association between positive rate of PTEN
      protein and LNM among Asians and Caucasians (both P > 0.05). Conclusion: Our
      findings indicate that decreased positive rate of PTEN protein may be linked to
      TNM staging and LNM in NSCLC, and it could be an important diagnostic biomarker
      of NSCLC.

PMID- 29578165
TI  - Predictive value of excision repair cross-complementation group 1 protein in
      locoregionally advanced nasopharyngeal carcinomas receiving cisplatin-based
      concurrent chemoradiotherapy.
AB  - Objective: To investigate the ability of excision repair cross-complementation
      group 1 (ERCC1) protein to predict cisplatin-based concurrent chemoradiotherapy
      (CCRT) response in locoregionally advanced nasopharyngeal carcinoma (NPC).
      Materials and Methods: The clinical data of 205 patients with locoregionally
      advanced NPC, who received cisplatin-based CCRT, were analyzed retrospectively.
      Immunohistochemical analysis was used to assess the ERCC1 expression in
      nasopharyngeal tumor tissues. Receiver operating characteristic (ROC) curve
      analysis, univariate and multivariate Cox proportional hazards analyses were
      performed to evaluate the association between ERCC1 expression and failure-free
      survival (FFS), overall survival (OS), locoregional-FFS (L-FFS), and distant-FFS
      (D-FFS). Results: Our results revealed that although the overall response rate in
      patients with high-ERCC1 expression (97.3%) and those with low-ERCC1 expression
      (100.0%) were not statistically different, but treatment-sensitive group
      displayed significantly lower ERCC1 expression in comparison to the treatment
      resistant group (P = 0.001). The Kaplan-Meier plots revealed that the low-ERCC1
      expression was significantly associated with better L-FFS, FFS, and OS of locally
      advanced NPC patients receiving cisplatin-based CCRT. Both univariate and
      multivariate analysis demonstrated that the ERCC1 expression, tumor node
      metastasis stage and performance status were independent predictors of OS and
      FFS. Conclusion: ERCC1 expression may be a useful predictive marker in patients
      with locoregionally advanced NPC, who are receiving cisplatin-based CCRT.

PMID- 29578166
TI  - The effect of temperature-control microwave on HELA and MG-63 cells.
AB  - Context: Hyperthermia has now been used to treat many kinds of solid
      malignancies. However, the applied thermal parameters about heat temperature and
      time varied all over the world, and no consensus about the optimal formula had
      been reached. Microwave ablation, as one of thermal ablation methods, is usually
      applied based on the fixed parameters of power and duration. As a result, too
      high temperature or overheating might not be avoided and excessive heating might
      cause some additional side effects to normal tissues. Aims: To explore the
      optimal parameters of power and duration for the HELA and MG-63 cells in vitro.
      Settings and Design: With a temperature-controlled microwave workstation, a
      microwave thermal ablation experiment was performed in vitro. Subjects and
      Methods: The HELA and MG-63 cells were heated with 40 degrees C, 45 degrees C, 50
      degrees C, 55 degrees C, and 60 degrees C lasting for 5-30 min, respectively.
      Then, the cell viability was detected using four methods: Flow cytometer assay,
      nicotinamide adenine dinucleotide-diaphorase staining, Calcein-acetoxymethyl
      ester staining immediately after treatment, and CCK-8 assay 24 h later. Results:
      The temperature-controlled microwave has an excellent ablation effect on both
      cell lines. Furthermore, when the thermal stimulation reached 55 degrees C 25 min
      and 55 degrees C 20 min for the HELA and MG-63 cells, respectively, or 60 degrees
      C 5 min for both, all the viability indexes indicated immediately devitalization.
      Conclusion: It presented a preliminary minimum lethal dose of heat was validated
      on the cellular level in vitro, which should be verified and corrected further in
      vivo.

PMID- 29578167
TI  - Overexpression of S100A4 protein may be associated with the development and
      progression of pancreatic cancer.
AB  - Aim: Accumulated evidence has suggested a relationship between S100A4 protein
      expression and the development and progression of pancreatic cancer (PC) while
      its role in diagnosis and prognosis of PC still keeps inconsistent. To obtain
      definitive associations between S100A4 and PC, a meta-analysis was conducted.
      Materials and Methods: The PubMed and Chinese National Knowledge Infrastructure
      databases were electronically searched to identify studies reporting an
      association between S100A4 protein and PC. Statistical analyses were undergone
      with the utilization of STATA version 12.0 software. Results: Nine clinical
      studies with a total of 545 tumor samples were included in the meta-analysis.
      Results revealed that increased S100A4 expression were associated with the tumor
      node-metastasis stages of PC (III-IV vs. I-II: odds ratio [OR] =5.50, 95%
      confidence interval [95% CI] =3.13-9.67, P < 0.001). Also, compared with 1-2
      histologic grade of PC samples, S100A4 protein was expressed more frequently in
      samples with 3-4 histologic grade (grades 1-2 vs. grades 3-4: OR = 2.57, 95% CI =
      1.05-6.24, P = 0.038). Conclusion: This meta-analysis showed that overexpression
      of S100A4 seems to be associated with tumor progression and poor prognosis of PC
      patients.

PMID- 29578168
TI  - Short-term outcomes after transition from Sweet to thoracoscopic esophagectomy:
      Our experience and cost analysis.
AB  - Objective: Thoracoscopic esophagectomy (TSE), as a minimally invasive technique,
      has obtained wide acceptance for treating esophageal cancer. In this study, we
      report our experience of the transfer from open sweet esophagectomy (OSE) to TSE
      and compare cost associated with the two approaches for esophageal cancer.
      Patients and Methods: Data were taken through a retrospective review of operative
      outcomes, complications and cost of 91 patients who underwent OSE or TSE for
      esophageal cancer from January 2012 to June 2014. Results: Among 91 patients, 48
      patients underwent TSE, and 43 patients underwent OSE. Patients dealt with TSE
      had significantly less blood loss (152 ml vs. 204 ml, P = 0.004), shorter chest
      drainage time (3.3 days vs. 4.5 days, P < 0.001), less patients admitted to the
      Intensive Care Unit after surgery (6.3% vs. 30.2%, P = 0.003), and lower
      incidence of respiratory complications (16.7% vs. 37.2%, P = 0.026). However, the
      operative time was statistically longer in TSE group (276.0 min vs. 207.4 min, P
      < 0.001). The total cost (Y61,817 vs. Y48,712, P < 0.001) and the day of surgery
      cost (Y29,701 vs. Y19,446, P < 0.001) were significantly higher in the TSE group.
      Conclusion: This study shows that TSE is a safe and acceptable alternative to
      OSE. TSE will be more competitive if its cost can be reduced.

PMID- 29578170
TI  - Association of toll-like receptors with the risk of oral squamous cell carcinoma.
AB  - Aim of Study: Association of toll-like receptors (TLRs) with the risk of oral
      squamous cell carcinoma (OSCC) from the published reports is still conflicting.
      This study was conducted to evaluate the relationship between TLRs and the risk
      of OSCC using meta-analysis method. Materials and Methods: The association
      studies were identified from PubMed and Cochrane Library on April 01 2015, and
      eligible investigations were included and synthesized using meta-analysis method.
      Result: Three reports were recruited into this meta-analysis for the association
      of TLRs with OSCC susceptibility. In this meta-analysis, we found that TLRs were
      not associated with OSCC susceptibility. However, in the sub-group analysis, we
      found that TLR-7 was associated with OSCC risk. Conclusion: TLR-7 was associated
      with OSCC risk. TLR-7 might be an indicator to predict the OSCC risk. However,
      more studies should be conducted to confirm it.

PMID- 29578169
TI  - Clinical research of goal-directed fluid therapy in elderly patients with radical
      resection of bladder cancer.
AB  - Objective: The aim of this study is to investigate the clinical effect of goal
      directed fluid therapy in elderly patients with radical resection of bladder
      cancer. Materials and Methods: Seventy-six elderly patients with radical
      resection of bladder cancer were selected from October 2012 to October 2014 and
      randomly divided into two groups, in which 38 patients received routine treatment
      as the control group and 38 patients received goal-directed fluid therapy based
      on routine treatment as the observation group. The treatment effect was compared
      between two groups. Results: The cardiac index, stroke volume variability, mean
      arterial pressure, central venous pressure, central venous oxygen saturation,
      oxygen supply index, oxygen consumption index, and oxygen uptake rate in
      observation group were distinctly higher than those in control group at T1, T2,
      T3, and T4 while the artery serum lactate and S100-beta were apparently lower
      than those in control group at T1, T2, T3, and T4. The urine volume and colloidal
      infusion were obviously elevated when compared with those in control group at T1,
      T2, T3, and T4 while the crystalloid infusion volume, total liquid infusion
      volume, hospitalization time, and expenses were significantly less than those in
      control group; further, similar tendency was also found regarding the
      complication incidences of nausea, vomiting, or hypotension in observation group.
      The postoperative flatus and postoperative food-taking times were visibly earlier
      than those in control group (both P < 0.05). Conclusion: The goal-directed fluid
      therapy is beneficial for stabilization of hemodynamic status and maintenance of
      oxygen balance of supply and demand, and it is worthy of clinical expansion for
      good microcirculation perfusion, reduction in therapeutic time and expenses of
      patients, and less complications and superior security.

PMID- 29578171
TI  - Effect of smoking on high-grade cervical cancer in women on the basis of human
      papillomavirus infection studies.
AB  - Purpose: We aimed, in the present study, to measure the risk related to the high
      grade cervical intraepithelial neoplasia grade 3 (CIN3) or worse (CIN3+) or
      worse/high-grade squamous intraepithelial lesions with respect to changes in
      human papillomavirus (HPV) and smoking status. Materials and Methods: A
      structured interview underwent for 7129 women. Then, we obtained their cervical
      cells and subjected to HPV testing. High-risk HPV infected and "no prevalent"
      cervical disease infected women were followed for cervical lesions up to 12 years
      (at baseline; n = 1531). Hazard ratios (HRs) for diagnosis of CIN3 (or worse) or
      worse/high-grade intraepithelial lesions were calculated along with the
      corresponding 95% confidence intervals (CIs). Results: Among high-risk HPV
      positive women, the conditions of long-term (more than 8 years) smokers and heavy
      (18 or more cigarettes/day) smokers are highly responsible for the increased risk
      for CIN3 or CIN3+. In the cases of persistent HPV-infected women, heavy smoking
      led to a higher risk for CIN3+ than those women who never smoked (HR, 2.31; 95%
      CI, 1.12-4.16). Conclusion: We concluded here that smoking leads to an enhanced
      risk of high-grade cervical lesions in persistent high-risk HPV-infected women.
      This makes a good understanding of smoking's role in cervical cancer.

PMID- 29578172
TI  - Effect of bevacizumab combined with chemotherapy at different sequences in the
      gastric-cancer-bearing nude mice.
AB  - Objective: To observe changes in the growth of fluorescence-labelled tumour cells
      in nude mice using small animal in vivo imaging technology and to compare the
      anti-tumour effects of the administration of bevacizumab monoclonal antibodies
      combined with chemotherapy at different time sequences. Materials and Methods:
      Different time sequences of administration of bevacizumab monoclonal antibodies
      combined with the 5-fluorouracil and cisplatin (FP) chemotherapy regimen were
      used for intervention treatment of tumour growth in a subcutaneous xenograft
      model of human gastric cancer in nude mice. Tumour growth, that is, tumour
      volume, was evaluated with the changes in fluorescence signal strength and the
      inhibition rate. Results: Compared with the control group (normal saline),
      experimental groups had a certain inhibition rate, while the tumour inhibition
      rate in the group with a bevacizumab treatment for 24 h followed by the FP
      chemotherapy regimen was the highest (68.42%). Moreover, the fluorescence signal
      strength changed significantly in all of the experimental groups. At the 3rd week
      of bevacizumab administration, the fluorescence signal value in the group with a
      bevacizumab treatment for 24 h followed by the FP chemotherapy regimen was the
      lowest, indicating this is the best treatment out of five groups. Conclusion:
      Bevacizumab monoclonal antibodies combined with chemotherapy had synergistic
      effects. The small animal in vivo imaging system could dynamically obtain long
      and short diameters of tumours and their fluorescence signal values; compared
      with traditional methods that calculate tumour inhibition rates by weighing
      tumours, this method was more sensitive and more objective for drug evaluation.

PMID- 29578173
TI  - Guiding values of multislice spiral computed tomography angiography in
      laparoscopic D2 radical gastrectomy of local advanced gastric carcinoma.
AB  - Objective: This study aims to investigate the application values of preoperative
      multislice spiral computed tomography angiography (MSCTA) in laparoscopic radical
      resection of gastric carcinoma (GC). Materials and Methods: A total of 108 GC
      patients were divided into Groups I (i.e., where preoperative MSCTA was
      performed; n = 60) and II (i.e., where preoperative MSCTA was not performed; n =
      48). Surgery was performed by the same group of surgeons. Results: Seven cases of
      blood vascular variation were detected in Group I during surgery, whereas four
      cases were detected in Group II. The operation time for Group I ([207 +/- 24]
      min) was shorter than that for Group II ([260 +/- 31] min) (95% confidence
      interval [95% CI]: -21.543--0.920, P = 0.044). The operation time of patients
      with gastric vascular anatomic variation in Group I ([189 +/- 49] min) was
      shorter than that of patients in Group II ([257 +/- 61] min) (95% CI: -99.68-
      3.201, P = 0.048). The differences in the number of lymph node dissection,
      average blood loss, eating time, complication rate, and postoperative hospital
      stay between the two groups was not statistically significant (P > 0.05).
      Conclusions: MSCTA before endoscopic radical resection exhibits guiding values in
      assessing blood vascular variations and shortening operation times.

PMID- 29578174
TI  - Effects of continued psychological care toward brain tumor patients and their
      family members' negative emotions.
AB  - Purpose: Numerous studies have confirmed that brain tumor patients and their
      family members frequently exhibit negative emotional reactions, such as anxiety
      and depression, during diagnosis and treatment of the disease. Family members
      experience increasing pressure as the year of survival of patient progress. The
      aim of this study was to investigate the effects of the continued psychological
      care (CPC) toward the brain tumor patients and their family members' emotions.
      Subjects and Methods: The asynchronous clinical control trial was performed, and
      162 brain tumor patients and their family members were divided into the control
      group and the intervention group. The control group was only performed the
      telephone follow-up toward the patients. Beside this way, the intervention group
      was performed the CPC toward the patients and their family member. The self
      rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used
      to measure the negative emotions of the patients and their family members, and
      the patients' treatment compliance and the incidence of seizures were compared.
      Results: The SAS and SDS scores of the intervention group on the 14 days, 28 days
      and 3 months of the CPC were significantly lower than the control group (P <
      0.05); the SAS and SDS scores of the intervention group after the intervention
      were significantly lower than those at the discharging (P < 0.05), the treatment
      compliance of the intervention group was significantly higher than the control
      group (P < 0.05), and the seizure incidence of the intervention group was
      significantly lower than the control group (P < 0.05). Conclusion: The CPC could
      effectively reduce the anxiety and depression among the brain tumor patients and
      their family members.

PMID- 29578175
TI  - TOX high mobility group box family member 3 rs3803662 and breast cancer risk: A
      meta-analysis.
AB  - Aims: Some studies suggested that TOX high mobility group box family member 3
      (TOX3) rs3803662 polymorphism was associated with the risk of breast cancer.
      However, the results were controversy. Therefore, in order to derive a more
      comprehensive estimation of the association between TOX3 rs3803662 polymorphism
      and breast cancer risk, we conducted a meta-analysis to investigate this
      relationship. Materials and Methods: An electronic literature search was
      conducted using the following database: PubMed, EMBASE, and China National
      Knowledge Infrastructure till to March 31, 2015. The strength of the associations
      between the TOX3 rs3803662 polymorphism and breast cancer risk in per alle model
      was measured by odds ratios (ORs) and 95% confidence intervals (CIs). Results: A
      statistically significant association between TOX3 rs3803662 polymorphism and
      breast cancer risk was fond. The data showed that TOX3 rs3803662 polymorphism
      could increase the risk of breast cancer (OR = 1.20; 95% CI: 1.16-1.25; P <
      0.00001). In the subgroup analysis of race, Caucasians, Asians, and Hispanics
      also showed increased breast cancer risk (OR = 1.21; 95% CI: 1.17-1.25; P <
      0.00001; OR = 1.20; 95% CI: 1.08-1.33; P = 0.0004; OR = 1.32; 95% CI: 1.12-1.57;
      P = 0.001). However, African-Americans with TOX3 rs3803662 polymorphism showed
      decreased breast cancer risk (OR = 0.95; 95% CI: 0.86-1.04; P = 0.28), although
      the result was not significant. When considered estrogen receptor (ER) status, we
      found that ER + subjects and ER - subjects all had increased breast cancer risk,
      if they carried this polymorphism (OR = 1.27; 95% CI: 1.19-1.35; P < 0.00001; OR
      = 1.12; 95%CI: 1.08-1.17; P < 0.00001). Similarly, both progesterone receptor
      positive (PR +) subjects and PR - subjects all showed increased breast cancer
      risk, if they carried this polymorphism (OR = 1.32; 95% CI: 1.17-1.49; P <
      0.00001; OR = 1.15; 95% CI: 1.09-1.23; P < 0.00001). Conclusions: This meta
      analysis suggested that TOX3 rs3803662 polymorphism was associated with increased
      breast cancer risk.

PMID- 29578176
TI  - Applications of nerve stimulator-guided thoracic paravertebral nerve block plus
      general anesthesia in small-incision lung cancer surgery.
AB  - Objective: The aim of the study was to investigate the application of nerve
      stimulator-guided thoracic paravertebral nerve block (TPVB) plus general
      anesthesia (GA) in small-incision lung cancer surgery. Methods: Forty patients
      scheduled for small-incision lung cancer surgery, the American Society of
      Anesthesiologists Grade I-II, were randomized into a TPVB-GA group (Group P) and
      a GA group (Group G), with 20 cases in each group. The dosage of general
      anesthetic, mean arterial pressure (MAP) at each time point, and heart rate (HR)
      of the two groups were recorded. The postoperative respiration recovery time,
      extubation time, incidence of adverse reactions, and postoperative visual analog
      scale (VAS) scores of the two groups were also observed. Results: Group P showed
      stable hemodynamics, and lower MAP and HR at each time point than Group G (P <
      0.05). The intraoperative dosage of general anesthetic in Group P was lower than
      that in Group G (P < 0.05). The respiration recovery time and extubation time in
      Group P were significantly shorter than those in Group G (P < 0.05); the
      incidence of agitation was significantly lower than that in Group G (P < 0.05).
      The VAS scores of Group P under quiet and cough status were also better than
      Group G (P < 0.05). Conclusions: Nerve stimulator-guided TPVB-GA is suitable for
      small-incision lung cancer surgery.

PMID- 29578177
TI  - The clinical benefit of epidermal growth factor receptor and human epidermal
      growth factor receptor 2 targeted agents adding to endocrine therapy in hormone
      receptor-positive breast cancer.
AB  - Objectives: Studies have suggested that the crosstalk between estrogen receptor
      and ErbB receptor is involved in endocrine therapy (ET) resistance, which might
      be overcome by drugs-targeting ErbB receptor. However, the results of clinical
      studies remain controversial. The aim of this meta-analysis was to evaluate the
      efficacy and safety of ErbB (mainly epidermal growth factor receptor and human
      epidermal growth factor receptor 2 [HER2]) inhibitors added to ET for hormone
      receptor-positive breast cancer patients. Materials and Methods: Eligible
      randomized clinical trials on ET with or without ErbB receptor-targeting
      inhibitors (ERTI) for hormone receptor-positive breast cancer were identified by
      searching the main electronic databases (up to July 2015). Revman 5.3 was used to
      analyze the outcomes extracted from the included trials. Results: In the overall
      population, ERTI failed to show any significant differences on overall response
      rate (ORR), clinical benefit rate (CBR), and overall survival (OS). However,
      improvement on progression-free survival (PFS) (hazard ratio [HR] 0.84, 95%
      confidence interval [CI] = 0.76-0.93, P = 0.0005) was observed. For the HER2+
      subgroup, ERTI could significantly improve ORR, CBR, PFS, OS, and time to
      progression compared to endocrine monotherapy. This improvement cannot be found
      in the HER2- subgroup. The risk of serious adverse events (SAEs) increased
      significantly when ERTI was present (RR = 2.09, 95% CI = 1.44-3.02, P < 0.0001).
      Conclusions: For HR+/HER2+ breast cancer, ERTI added to ET can significantly
      improve the clinical efficacy with the cost of increasing SAE.

PMID- 29578178
TI  - Comparison of short-course with long-course preoperative neoadjuvant therapy for
      rectal cancer: A meta-analysis.
AB  - Aim: This study attempted to compare the prognostic performance of short- and
      long-course preoperative treatments for neoadjuvant therapy of rectal cancer by
      meta-analysis. Methods: Electronic databases of PubMed and Embase were searched
      for eligible studies updated to February 29, 2016. Studies were included based on
      several predefined inclusion criteria. Quality assessment was carried out
      according to the Cochrane Collaboration recommendations in Cochrane handbook.
      Outcomes such as 1-5 survival rates, death rate, recurrence rate, complication
      rate, and distant metastasis were evaluated. Odds ratio (OR) with the
      corresponding 95% confidence interval (CI) was used to calculate the pooled
      results. Subgroup analysis stratified by radiotherapy (RT) and chemoradiotherapy
      (CRT) was performed. Publication bias was detected based on Egger's test.
      Sensitive analysis was also performed. Results: Eight studies were included, and
      they were randomized controlled trials or controlled clinical trials. The
      included studies involved a total of 1475 patients (short treatment: n = 665;
      long treatment: n = 810). No significant difference was detected in each outcome
      between the short- and long-course preoperative treatments. Subgroup analysis
      indicated that the outcome of distant metastasis was significantly higher in long
      course RT, compared with the short-course RT (OR = 2.65, 95% CI: 1.05, 6.68). No
      significant publication bias was observed. Sensitive analysis did not show any
      reverse result. Conclusion: Short- and long-course preoperative treatments seem
      comparable for management of rectal cancer, in terms of outcomes such as
      survival, recurrence, and complications. However, long-course RT might increase
      risk of distance metastasis, compared to short-course RT.

PMID- 29578179
TI  - Solanum nigrum polysaccharide inhibits tumor growth in H22-bearing mice through
      regulation of caspase-3 and bcl-2.
AB  - Objective: The objective of this study was to investigate the effect of Solanum
      nigrum polysaccharides (SNPs) on tumor growth in H22 hepatocarcinoma cells
      bearing mice and explore the mechanism by focusing on the regulation of the
      expression of caspase-3 and bcl-2. Materials and Methods: Totally, 50 mice
      bearing with H22 cells were randomly divided into five groups: Model group,
      cyclophosphamide group (CTX, 30 mg/kg), SNP groups with low, medium, and high
      doses of SNP (30, 60, and 120 mg/kg). Twenty-four hours after inoculation of H22
      cells, CTX or SNP were given by gavage once a day for 10 days. The growth of
      tumor was observed. The tumor inhibition rate, indexes of the spleen and thymus
      were calculated. The immunohistochemical method was used for the determination of
      caspase-3 and bcl-2 expression in the tumor tissue. Results: SNP (30, 60, and 120
      mg/kg) reduced the average tumor weight compared with that in model group in a
      dose-dependent manner, and the tumor inhibition rates were 37.73%, 38.24%, and
      42.60%, respectively. In addition, SNP dose dependently increased the index of
      the thymus compared with that of the CTX group. Immunohistochemistry results
      showed that the protein expression of caspase-3 in SNP groups was higher, but the
      expression of bcl-2 was lower than that in model group in a dose-dependent
      manner. Conclusion: SNP inhibited the growth of tumor in H22-bearing mice and
      protected the immune organ. The mechanism underlying the inhibition of tumor
      might be related to the upregulation of caspase-3 and downregulation of bcl-2.

PMID- 29578180
TI  - Effect of lenalidomide on the human gastric cancer cell line SGC7901/vincristine
      Notch signaling.
AB  - Aim of Study: To examine the function of lenalidomide (LEN) on the human
      multidrug resistance (MDR)-type gastric cancer line SGC7901/vincristine (VCR) via
      regulating Notch signaling. Materials and Methods: Quantitative polymerase chain
      reaction was used for checking the genes of Notch, DNA methyltransferase (DNMT),
      RBP-J, Hes1/5, Deltex1, MDR/multidrug resistant protein (MRP); the cell
      proliferation and cell death were detected by cell counting kit-8 (CCK8)
      staining, Ki-67 expression, and propidium-iodide staining, and methylated DNA
      immunoprecipitation assay (MeDIP) was used for checking the 5 mC enrichment,
      indicating the DNA methylation of the Notch2 gene loci. Results: LEN reduced the
      mRNA expression of Notch2 (P < 0.01) and increased the expression of the DNMT3A
      (P < 0.001) in SGC7901/VCR cell, suggesting the involvement of epigenetic
      regulation by DNMT3A on Notch2 gene expression. Consistently, Notch2 gene
      expression showed no obvious change between the LEN treatment and the control
      when the DNMT3A was knockdown using the interference of shRNA. The modulation of
      DNA methylation process on gene expression was then confirmed by 5 mC enrichment
      on Notch2 gene loci after LEN treatment. Furthermore, LEN could suppress the
      downstream genes in Notch2 signaling including RBP-J (P < 0.05), Hes1 (P <
      0.001), and Deltex1 (P < 0.01). Due to the changes of gene expression pattern in
      Notch pathway, LEN showed a phenotype of cell proliferation suppression using
      CCK8 staining. Meanwhile, the expression of the genes associated with MDR and MRP
      was also significantly decreased (MDR, P < 0.01; MRP, P < 0.001) after LEN
      treatment. Therefore, inhibition of cell proliferation by LEN via Notch2
      signaling combined with the MDR/MRP expression modulation contributes to the
      efficacy of LEN on the gastric cancer cell line SGC7901/VCR. Conclusion: The data
      implicate that LEN would be an effective chemical for the therapy of drug
      resistant human gastric cancer cell and the gastric cancer patients.

PMID- 29578181
TI  - Identification of key genes related to high-risk gastrointestinal stromal tumors
      using bioinformatics analysis.
AB  - Aim: The purpose of this study was to identify predictive biomarkers used for
      clinical therapy and prognostic evaluation of high-risk gastrointestinal stromal
      tumors (GISTs). Materials and Methods: In this study, microarray data GSE31802
      were used to identify differentially expressed genes (DEGs) between high-risk
      GISTs and low-risk GISTs. Then, enrichment analysis of DEGs was conducted based
      on the gene ontology and kyoto encyclopedia of genes and genomes pathway
      database. In addition, the transcription factors and cancer-related genes in DEGs
      were screened according to the TRANSFAC, TSGene, and TAG database. Finally,
      protein-protein interaction (PPI) network was constructed and analyzed to look
      for critical genes involved in high-risk GISTs. Results: A total of forty DEGs
      were obtained and these genes were mainly involved in four pathways, including
      melanogenesis, neuroactive ligand-receptor interaction, malaria, and
      hematopoietic cell lineage. The enriched biological processes were related to the
      regulation of insulin secretion, integrin activation, and neuropeptide signaling
      pathway. Transcription factor analysis of DEGs indicated that POU domain, class
      2, associating factor 1 (POU2AF1) was significantly downregulated in high-risk
      GISTs. By constructing the PPI network of DEGs, ten genes with high degrees
      formed local networks, such as PNOC, P2RY14, and SELP. Conclusions: Four genes as
      POU2AF1, PNOC, P2RY14, and SELP might be used as biomarkers for prognosis of high
      risk GISTs.

PMID- 29578182
TI  - Diffuse large B-cell lymphoma with concurrent hepatitis B virus infection in the
      MabThera era: Unique clinical features and worse outcomes.
AB  - Aim of Study: Hepatitis B virus (HBV) infection is a risk factor in diffuse large
      B-cell lymphoma (DLBCL); however, little is known other than the prevalence
      evidence. In addition, the impact of HBV infection to DLBCL remains
      controversial. The purpose of this study was to investigate the HBV infection
      status of 136 patients with DLBCL, analyze the clinical property of HBV-infected
      patients, and determine the effects of HBV infection to the outcomes of DLBCL
      patients. Materials and Methods: A retrospective analysis was performed in our
      center from January 2007 to December 2014. A total of 136 DLBCL patients
      accepting three or more cycles of cyclophosphamide, doxorubicin, vincristine, and
      prednisolone (CHOP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and
      prednisolone (R-CHOP) regimen were analyzed. Results: Of the 136 patients, 55
      were HBV-infected and their clinical features were different in several aspects
      such as young onset age (P = 0.027), frequent occurrence of B symptom (P =
      0.009), and advanced disease stage (Stage III/IV, P = 0.037). Besides more HBV
      infected patients exhibited lower levels of peripheral lymphocyte-to-monocyte
      ratio (<=2.0). In the survival assessment, HBV-infected patients were worse in
      both progression-free survival (PFS) (P = 0.001) and overall survival (OS) (P =
      0.030) in MabThera treated group, but get a draw in CHOP regimen group (P = 0.658
      in PFS and P = 0.798 in OS). Sort of surprisingly, HBV-infected patients treated
      with MabThera did not have a superior to the traditional regimen in both PFS (P =
      0.969) and OS (P = 0.875). Conclusion: DLBCL patients with HBV infection are
      subset with unique clinical characters and have worse outcomes. The benefit of
      MabThera to HBV-infected DLBCL patients was uncertain thus have to be weighed
      against the costs before application.

PMID- 29578183
TI  - Four case reports on pelvic tumors with deep venous thromboses as main symptoms
      and literature review.
AB  - To probe into the reasons for misdiagnoses of pelvic tumor as deep venous
      thromboses as well as the diagnostic methods and effective treatments on pelvic
      tumor. Four case reports on misdiagnosing pelvic tumor as deep venous thromboses
      and further analysis on the causes of misdiagnosis, diagnosis, and treatment with
      the literature study. The four cases were misdiagnosed as pelvic tumor, which
      actually were fibroneuroma, myxo.fluidity liposarcoma, moderately differentiated
      squamous cell carcinoma, and synovial sarcoma, respectively. The tumor in first
      case was completely removed, and the tumor in other three cases, which were
      malignant tumors, were resected when the tumors shrank with clear boundary and
      less blood supply after applied with 3. cycles of intra.arterial chemotherapy via
      an implanted pumpies. Pelvic tumor usually show up or is misdiagnosed as deep
      venous thromboses for its untypical clinical manifestation, so it should be on
      the alert for pelvic tumor when deep venous thromboses occurs. Tumor resection is
      preferred for benign tumor, and intra.arterial intervention chemotherapy should
      be applied first for malignant tumor followed by surgery.

PMID- 29578184
TI  - Uterine metastases originating from a pulmonary inflammatory myofibroblastic
      tumor.
AB  - Pulmonary inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor,
      and is considered an inflammatory pseudotumor. Here, we report of a 37-year-old
      woman with severe cough and stridor who was diagnosed with primary IMT of the
      lungs, with adenocarcinoma in situ based on the pathology in December 2012. A
      year later, transabdominal ultrasonography demonstrated a solid mass in the
      uterine wall that was initially diagnosed as a leiomyoma. However, postoperative
      histological examination and immunohistochemical staining revealed it as a
      uterine metastasis of the lung IMT. One year thereafter, the patient died of the
      lung tumor.

PMID- 29578185
TI  - Hypofractionated postoperative irradiation in localized renal cell cancer: A case
      report and pertinent literature review.
AB  - For localized the incidence of renal cell carcinoma (RCC), nephrectomy is the
      standard treatment. As RCC is generally regarded as a radiation-resistant tumor,
      the value of postoperative adjuvant radiotherapy is controversial. However, with
      new advance in radiotherapy (i.e., three-dimensional conformal radiation therapy
      [3DCRT] and intensity-modulated radiation therapy [IMRT]), target volume
      delineation, intensity modulation in treatment planning, and treatment delivery
      are more accurate with fewer adverse effect. A right renal tumor was identified
      in a 50-year-old man during a routine examination. T1N0M0 RCC was clinically
      diagnosed as the tumor was 3 cm * 3.5 cm and well-enhanced with intravenously
      infused contrast material in the arterial phase on computed tomography (CT). No
      metastases to regional lymph nodes or distant sites were evident. 3DCRT after the
      operation was carried out. A total dose of 50 Gy in 20 fractions over 28 days was
      delivered using a 15-MV X-ray. No clinical acute or chronic side effects were
      recorded during or after treatment, which was well tolerated. After radiotherapy,
      the patient came back to the hospital for a check regularly, with no evidence of
      recurrence and metastasis more than 11 years, and the CT for abdominal showed
      partial function of the right renal remained. The present case showed a good
      response with recovery after CRT of 50 Gy in 20 fractions for postoperative RCC.
      Although further experiences and longer follow-up are mandatory to conclude the
      optimal treatment schedule and efficacy of CRT for RCC, postoperative
      radiotherapy definitely reduces locoregional recurrences and with acceptable
      gastrointestinal toxicity if modern techniques (CRT and IMRT) are utilized.

PMID- 29578186
TI  - Contrast-enhanced ultrasound imaging characteristics of malignant transformation
      of a localized type gallbladder adenomyomatosis: A case report and literature
      review.
AB  - Gallbladder adenomyomatosis (GAM) is an acquired, reactive, tumor-like condition.
      Malignant transformation is extremely rare, and imaging features during contrast
      enhanced ultrasound (CEUS) have not been described before. Herein, we describe a
      73-year-old Asian man who had been diagnosed with gallbladder carcinoma by
      conventional ultrasonography (US). Based on additional radiological findings, we
      believed that it was a localized adenomyomatosis. However, the histopathological
      diagnosis was adenocarcinoma originate from adenomyomatosis with serosal
      invasion. We believe this is the first case of adenocarcinoma derived from GAM
      with characteristics of CEUS findings. This case is presented to indicate a
      clinical awareness of malignant transformation of GAM and discuss the radiology
      significance with an emphasis on CEUS.

PMID- 29578187
TI  - Primary renal synovial sarcoma: A case report and literature review.
AB  - Synovial sarcomas (SSs) are very rare, poorly studied tumors that generally
      occurs around joint and muscle tendons. Primary SSs of the kidney are even rarer,
      accounting for <2% of all malignant renal tumors. We report the case of a 44-year
      old man who was diagnosed with primary renal SS on the basis of imaging,
      histopathological, and immunohistochemical examination. We also present a
      comprehensive review of the literature, with a focus on the differential
      diagnosis and treatment of renal tumors.

PMID- 29578188
TI  - Spectrum of hyperosmolar hyperglycaemic state in neurology practice.
AB  - Background & objectives: Hyperosmolar hyperglycaemic state (HHS) is a medical
      emergency, but there is a paucity of studies reporting the spectrum of
      neurological manifestations of HHS. We, therefore, report the neurological
      spectrum, triggering factors and outcome of HHS in general neurology practice.
      Methods: The records of the patients with HHS were extracted from computerized
      hospital information system and those managed currently were prospectively
      included. The demographic, clinical manifestations, duration of diabetes and
      precipitating events such as infection, stress and stroke were noted. Patients
      with HHS were categorized into seizure, movement disorder and encephalopathy
      groups. Their electroencephalography, magnetic resonance imaging (MRI) findings
      and outcome were noted. Results: There were 17 patients with HHS (age range 40
      and 75 yr) and seven were females. Seven patients were diabetic for five years,
      one for four years, one for one year and four were diagnosed after the occurrence
      of HHS. Four patients had epilepsia partialis continua persisting for 72-360 h,
      one patient had focal seizures and his MRI revealed T2 hyperintensity in frontal
      region in one patient and cerebellar vermian hyperintensity in another. All the
      five patients improved, but two had neurological deficits on discharge. Nine
      patients had encephalopathy which was precipitated by stroke in six patients,
      urinary infections in two and meningitis in one. Three females had hemichorea
      hemiballismus syndrome, which was triggered by infections. Abnormal movements
      lasted 5-10 days and responded to correction of hyperosmolarity. Nine out of 17
      patients improved completely whereas the remaining eight had partial recovery,
      these patients had stroke, ventilator-related complications or
      meningoencephalitis. Interpretation & conclusions: The most common presentation
      of HHS was encephalopathy (9) followed by seizure (5) and hemichorea
      hemiballismus syndrome (3) which responded to the correction of hyperosmolar
      state.

PMID- 29578189
TI  - Effect of multilevel lower-limb botulinum injections & intensive physical therapy
      on children with cerebral palsy.
AB  - Background & objectives: Botulinum toxin is considered as an effective treatment
      for spasticity in children with cerebral palsy (CP). However, there are only a
      few long-term studies, and the effects on motor function have been inconclusive.
      Moreover, due to its high cost and need for intensive post-injection therapy,
      utility in context of developing nations has not been established. This
      retrospective study was undertaken to assess the long term effects of botulinum
      toxin-A with physical therapy in children with CP. Methods: This retrospective
      study was conducted at a tertiary care centre in India, where a limited supply of
      botulinum toxin was introduced in the year 2009. It was used in a selective group
      of patients with CP along with intensive physical therapies. All children who
      received lower-limb botulinum injections over a 42-month period were analyzed.
      For evaluation of treatment effect, the measurement at 1st pre-injection
      assessment and the last measurements, i.e. 12 wk after last injection received by
      that child were compared. Results: Twenty nine patients (20 males, median age 51
      months) received 69 sessions of botulinum toxin injections in the lower limbs
      over a 42-month period. Thirteen patients were diplegic, 10 were quadriplegic,
      five were triplegic and one was hemiplegic. There was a significant improvement
      in pre- and post-injection scores on Observational Gait Scale (right side 7.1+/
      3.6 to 10.7+/-3.7, left side 6.7+/-3.5 to 9.9+/-3.4), Gross Motor Function
      Measure Scale (47.9+/-17.7 to 67.6+/-17.2), Modified Ashworth Scale, passive
      range of motion and Gross Motor Function Classification System. Most of the
      patients showed gain in motor milestones as well. Interpretation & conclusions:
      Our results showed that judicious use of botulinum injections along with
      intensive physio/occupational therapies could yield good results in children with
      CP.

PMID- 29578190
TI  - Uromodulin rs4293393 T>C variation is associated with kidney disease in patients
      with type 2 diabetes.
AB  - Background & objectives: Uromodulin, a UMOD gene encoded glycoprotein is
      synthesized exclusively in renal tubular cells and released into urine. Mutations
      lead to uromodulin misfolding and retention in the kidney, where it might
      stimulate cells of immune system to cause inflammation and progression of kidney
      disease. Genome-wide association studies (GWAS) have identified UMOD locus to be
      associated with hypertension and diabetic nephropathy (DN). In this study, we
      investigated the association between rs4293393 variation in UMOD gene and
      susceptibility to kidney disease in individuals with type 2 diabetes mellitus
      (T2DM). Methods: A total of 646 individuals, 208 with T2DM without evidence of
      kidney disease (DM), 221 with DN and 217 healthy controls (HC) were genotyped for
      UMOD variant rs4293393T>C by restriction fragment length polymorphism. Serum
      uromodulin levels were quantified by enzyme-linked immunosorbent assay. Results:
      A significant difference was found in genotype and allelic frequency among DM, DN
      and HC. TC+CC genotype and C allele were found more frequently in DN compared to
      HC (33.9 vs 23.0%, P=0.011 and 20.1 vs 12.9%, P=0.004, respectively). Compared to
      DM, C allele was found to be more frequent in individuals with DN (20.1 vs 14.7%,
      P=0.034). Those with DN had higher serum uromodulin levels compared to those with
      DM (P=0.001). Serum uromodulin levels showed a positive correlation with serum
      creatinine (r=0.431; P<0.001) and negative correlation with estimated glomerular
      filtration rate (r=-0.423; P<0.001). Interpretation & conclusions: The frequency
      of UMOD rs4293393 variant with C allele was significantly higher in individuals
      with DN. UMOD rs4293393 T>C variation might have a bearing on susceptibility to
      nephropathy in north Indian individuals with type 2 diabetes.

PMID- 29578191
TI  - Unenhanced renal magnetic resonance angiography in patients with chronic kidney
      disease & suspected renovascular hypertension: Can it affect patient management?
AB  - Background & objectives: Renal artery stenosis (RAS) is an important cause of
      severe hypertension in patients with chronic kidney disease (CKD). It is
      important to detect RAS early as it can reverse hypertension and stop rapid
      deterioration of renal function. The potential drawbacks of various imaging
      modalities used to detect RAS including contrast-related adverse effects
      associated with diagnostic angiography have led to increasing interest in
      unenhanced magnetic resonance (MR) renal angiography. The aim of this study was
      to detect and grade RAS in patients with CKD and suspected renovascular
      hypertension using unenhanced MR angiography (UMRA) and to identify patients with
      significant RAS (>70%) who would subsequently require further investigation and
      revascularization. Methods: Thirty five CKD patients with suspected RAS were
      subjected to UMRA using non-contrast MR angiography of ArTery and VEins 3D True
      fast imaging with steady state precession technique over a three year period.
      Patients with RAS >70 per cent on UMRA were subjected to digital subtraction
      angiography (DSA) with intervention if indicated. Results: In all, 76 renal
      arteries were evaluated using UMRA in 35 patients, of which 18 arteries showed
      stenosis and 11 were haemodynamically significant (eight patients). Seven
      patients (10 renal arteries) underwent DSA. Interpretation & conclusions: An
      association between UMRA and DSA findings was obtained in six patients (nine
      renal arteries), and these patients were stented. Post-procedure follow up showed
      good improvement in blood pressure and renal function. UMRA was found to be a
      useful non-invasive imaging modality to detect RAS in CKD patients. It can
      identify patients who require further invasive angiography and revascularization.

PMID- 29578192
TI  - Comparison of radiofrequency ablation alone & in combination with percutaneous
      ethanol injection for management of hepatocellular carcinoma.
AB  - Background & objective: It has been shown that the combined use of alcohol before
      radiofrequency ablation (RFA) helps to augment the therapeutic advantage of RFA.
      The present study was conducted to compare the outcome of treatment with RFA
      alone and RFA with alcohol as ablative technique in patients with small
      hepatocellular carcinomas (HCCs), who were not candidates for surgery. Methods:
      Fifty patients with chronic liver disease and concurrent HCC were enrolled in
      this prospective study. The patients were treated with either RFA alone (n=25) or
      RFA combined with alcohol (n=25). Patient outcome was evaluated, and the tumour
      recurrence and survival of the patients were assessed in the two groups. Results:
      The survival rates at six months in patients who completed at least six months of
      follow up were 84 and 80 per cent in patients treated with RFA alone and
      combination therapy, respectively. During the follow up period, 11 and four
      patients treated with RFA alone showed local and distant intrahepatic tumour
      recurrence, respectively. All local recurrences were at one to 18 months of the
      follow up period. The distant recurrences occurred at 6-36 months of the follow
      up period. During the follow up period, eight and six patients treated with
      combination therapy showed local and distant intrahepatic tumour recurrence,
      respectively. All local recurrences were at 1.5-15 months during the follow up
      period. The distant intrahepatic recurrences occurred at 6-72 months during the
      follow up period. Interpretation & conclusions: No significant difference was
      seen between the survival time of the patients treated with RFA alone and RFA
      with alcohol as well as in the local recurrences and distant intrahepatic
      recurrences in RFA compared to RFA and alcohol group patients. Combined use of
      RFA and alcohol did not improve the local tumour control and survival in patients
      with HCC compared to RFA alone.

PMID- 29578193
TI  - Interlink between cholesterol & cell cycle in prostate carcinoma.
AB  - Background & objectives: Earlier reports have shown hypocholesterolaemia in
      cancer patients and high number of lipid rafts in cancer cells. The primary
      objective of this study was to compare the intracellular cholesterol turnover in
      non-cancerous (benign) prostatic hyperplasia (BPH) and carcinoma prostate (CAP)
      with normal prostate cells obtained from patients undergoing radical cystectomy
      for carcinoma bladder (sham control). Methods: ELISA-based estimation of prostate
      specific antigen (PSA), evaluation of expression of low-density lipoprotein
      receptor (LDLR), peripheral-type benzodiazepine receptor (PBR) and cyclin E,
      immunohistochemistry and confocal microscopy, measurement of integrated optical
      density of the diaminobenzidine (DAB)-stained immunohistograms, isolation of
      nucleus and cell cytoplasm from prostate tissue by ultracentrifugation followed
      by estimation of cholesterol spectrophotometrically in isolated nuclear and
      cytoplasmic fractions were performed. Results: Seventy five individuals, 25 for
      each group (BPH n=25; CAP n=25 and sham control n=25), were included in the
      study. Cholesterol was increased in the cytoplasm and nucleus of the prostate
      cancer cells along with elevated expression of LDLR. Increased cholesterol
      concentration in the cell nucleus was found comparable with the increased
      expression of cholesterol transporter viz. PBR in the prostate tumour tissues as
      compared to its expression in normal prostate cells obtained from individuals
      undergoing radical cystectomy for carcinoma bladder. Cell cycle protein cyclin E
      was also highly expressed in cancer tissues. Interpretation & conclusions: The
      present findings along with increased expression of cell cycle protein cyclin E
      in the cell nucleus of the tumour tissue suggested the possibility of an
      intriguing role of cholesterol in the mechanism of cell cycle process of prostate
      cell proliferation.

PMID- 29578194
TI  - Effect of bone bank processing on bone mineral density, histomorphometry &
      biomechanical strength of retrieved femoral head.
AB  - Background & objectives: Standard processing of the bone grafts involves deep
      freezing and sterilization with gamma irradiation which may alter mechanical
      properties of the bone graft. This study was aimed at measuring the effect of
      bone bank processing on the mechanical properties of bone allograft and its
      correlation with bone mineral density [BMD, dual-energy X-ray absorptiometry
      (DEXA Scan)] and histomorphometric indices. Methods: Femoral heads retrieved from
      patients undergoing hip replacement surgeries were used as the material. Twenty
      femoral heads were under taken in the study. Each femoral head was cut into two
      equal cubes. One cube was subjected to BMD measurement using DEXA Scan followed
      by unilateral compression test. Histomorphometric indices such as trabecular
      number (Tb. N.), trabecular separation (Tb. S.), trabecular thickness (Tb. T.)
      and bone volume (B.V.) were calculated on the same specimen by a computer
      software. The other cube was kept in deep freezer (-76 degrees C) for a minimum
      of three weeks, followed by gamma irradiation and subjected to similar tests.
      Results: Results were compared in pre- and post-processed bone specimens. A
      significant loss of biomechanical strength (P<0.001) with mean a loss of 18.90
      per cent was found in post-processed samples in uniaxial compression tests.
      Similarly, BMD (mean decrease by 13.8%, P<0.01) and histomorphometric indices
      such as Tb. T. (mean decrease by 12.37%, P<0.01), Tb. S. (mean increase by
      12.60%, P<0.001) and B.V. (mean decrease by 20.84%, P<0.01) were found. However,
      Tb. N. was not significantly affected. Interpretation & conclusions: The current
      method of processing of bone allografts i.e. deep-freezing and gamma irradiation
      appeared to cause a significant reduction in the biomechanical strength of
      allogenic bone which was more suitable to be use in the morselized form.
      Appropriate consideration for decreased strength needs to be given when using
      allogenic bone graft as a structural graft.

PMID- 29578195
TI  - Assessment of osteoporotic fracture risk in urban Indian population using
      quantitative ultrasonography & FRAX tool.
AB  - Background & objectives: There have been studies around the world on the
      prevalence of osteoporosis and its related risk factors, but there have been
      limited studies on risk factors and osteoporosis in the Indian population. In
      this study, the incidence of osteoporosis and the associated clinical risk
      factors (CRFs) were studied in the urban Indian population. Methods: Bone mineral
      density of 445 individuals >38 yr of age using qualitative ultrasound (QUS) was
      assessed. The patients were also questioned regarding the presence of the various
      CRFs as per the FRAX tool. The patients were categorized into normal, osteopenia
      and osteoporosis groups on the basis of T-score from QUS. Results: There were 223
      males and 222 females in this study. Sex was significantly associated with T
      score (P<0.001). Forty (8.99%) patients were osteoporotic, 265 (59.55%) were
      osteopenic and the remaining 140 (31.46%) were normal. A significant association
      of T-score was found with parent history of fracture (P<0.05), rheumatoid
      arthritis (P<0.05) and secondary osteoporosis (P<0.05). Previous history of
      fracture's association was not found to be significant. Smoking, alcohol intake
      and steroid intake were not found to be significantly associated with T-scores.
      Interpretation & conclusions: The incidence of osteoporosis was found to be high
      in the urban Indian population. More care and attention should be targeted
      towards elderly, especially the ones with the risk factors to prevent
      osteoporosis in future.

PMID- 29578196
TI  - Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical
      Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index
      (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for
      assessing disease activity in patients with rheumatoid arthritis at initial
      presentation.
AB  - Background & objectives: In patients with rheumatoid arthritis (RA), disease
      severity assessment is done using Disease Activity Score in 28 joints with ESR
      (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an
      online calculator. There is a need to validate rapid methods of disease severity
      assessment for routine daily use. This study was conducted to compare DAS28,
      Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire
      Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3
      measures (RAPID3) to assess the disease activity in patients with RA. Methods: We
      prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100
      consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naive
      adult patients with RA seen during January 2013 and June 2014 at a tertiary care
      teaching hospital in south India. Results: The mean age of the patients was
      42.1+/-11.6 yr, there were 82 females. The median [interquartile range (IQR)]
      symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQ-DI
      and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13
      19), respectively. A significant positive correlation was observed between DAS28
      and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and
      RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between
      DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI
      (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust.
      Interpretation & conclusions: In adult patients with RA, in the setting where
      illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of
      severity of disease at the time of initial presentation.

PMID- 29578197
TI  - Immunohistochemical expression of hypoxia-inducible factor-1alpha in stromal
      cells of vaginal tissue in post-menopausal women with pelvic organ prolapse.
AB  - Background & objectives: Pelvic organ prolapse (POP) is a common medical
      condition that affects adult women of different ages. The support of a normal
      pelvic floor is the result of complex interactions between ligaments, muscles,
      connective tissue and vaginal walls. Hypoxia and oxidative stress can reduce
      protein synthesis in the pelvic muscles that may contribute to muscular atrophy.
      Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcriptional activator
      which, expressed in response to hypoxia, activates a number of genes involved in
      cellular response to hypoxia. However, a potential role of hypoxia and oxidative
      stress in pathogenesis of POP is not known. This study was aimed to compare the
      level of HIF-1alpha immunohistochemical expression in the vaginal stromal cells
      of postmenopausal women with and without POP. Methods: Samples of the vaginal
      tissue from 120 menopausal women were obtained during surgery, and
      immunohistochemical expression of HIF-1alpha was assessed. There were 60 women
      with POP while 60 women in the control group were without prolapse but with
      benign gynaecological diseases. Results: In post-menopausal women with prolapse,
      significant differences were observed in the number of HIF-1alpha-positive
      stromal cells in the vaginal tissue compared to the control group. There was a
      significant increase in the number of HIF-1alpha in the stromal cells of the
      vaginal tissue in women with prolapse. Interpretation & conclusions: Difference
      in expression of HIF-1alpha in stromal cells of the vaginal tissue in the post
      menopausal women with and without POP suggests that prolonged hypoxia probably
      has an important role in the aetiopathogenesis of POP.

PMID- 29578198
TI  - Impact of attendance in a daycare centre on depression among elderly in rural
      Puducherry: A pre- & post-intervention study.
AB  - Background & objectives: Depression is higher in the elderly and in the rural
      areas in India. There is a need for interventions to reduce depression among the
      elderly and improve their quality of life (QOL). This study was conducted to
      assess the impact of attendance at a community-based daycare centre in rural
      Puducherry, India, on depression, cognitive impairment (CI) and QOL of the
      elderly. Methods: This was a before and after intervention study with a daycare
      centre set up in the village Thondamanatham in Puducherry, India, between January
      2013 and January 2014. Socializing activities were held at the centre with
      psychological counselling. Depression was measured using Geriatric Depression
      Scale (GDS, short form), CI using the Hindi Mini-Mental Status Examination and
      QOL using WHO QOL BREF. Results: There were 99 males and 164 females; of whom
      42.2 per cent attended the daycare centre at least once a month. Significantly
      higher proportions of elderly had depression among those with lower frequency of
      attendance at the daycare centre. Irrespective of the pre-intervention status,
      attendance at the daycare centre reduced the probability of depression by about
      51 per cent. There was an improvement in the WHO QOL scores in the social domain
      among those who attended more than once a month. Interpretation & conclusions:
      GDS scores decreased and WHO QOL scores increased with increasing attendance at
      the daycare centre. Thus, the intervention was found to be effective in reducing
      depression and improving QOL of the elderly.

PMID- 29578200
TI  - Epigallocatechin gallate & curcumin prevent transforming growth factor beta 1
      induced epithelial to mesenchymal transition in ARPE-19 cells.
AB  - Background & objectives: Proliferative vitreoretinopathy (PVR) is characterized
      by the presence of epiretinal membrane (ERM), which exerts traction and detaches
      the retina. Epithelial to mesenchymal transition (EMT) of the retinal pigment
      epithelial (RPE) cells underlies ERM formation. Adjuvant therapies aimed at
      preventing recurrence of PVR after surgery mostly failed in clinical trials. This
      study was aimed to evaluate the anti-EMT properties of bio-active compounds
      epigallocatechin gallate (EGCG), curcumin and lycopene as inhibitors of EMT
      induced by transforming growth factor beta 1 (TGF-beta1) in cultured ARPE-19
      cells. Methods: ARPE-19 cells were treated with TGF-beta1 alone or co-treated
      with EGCG (1-50 MUM), lycopene (1-10 MUM) and curcumin (1-10 MUM). The mRNA and
      protein expression of EMT markers, alpha-smooth muscle actin, vimentin, zonula
      occludens-1 and matrix metalloproteinase-2 (MMP-2), were assessed by reverse
      transcription polymerase chain reaction/quantitative polymerase chain reaction
      and immunofluorescence/enzyme linked immunosorbent assay. Activity of MMP-2 was
      assessed by zymography. Functional implications of EMT were assessed by
      proliferation assay (MTT assay) and migration assay (scratch assay). Western-blot
      for phosphorylated Smad-3 and total Smad-3 was done to delineate the mechanism.
      Results: EGCG and curcumin at 10 MUM concentration reversed EMT, inhibited
      proliferation and migration through Smad-3 phosphorylation, when induced by TGF
      beta1 in ARPE-19 cells. Lycopene did not prevent EMT in ARPE-19 cells.
      Interpretation & conclusions: EGCG and curcumin are potent in preventing EMT
      induced by TGF-beta1 in ARPE-19 cells and therefore, proposed as potential
      molecules for further pre-clinical evaluation in PVR management.

PMID- 29578201
TI  - Use of covered stents in simultaneous management of coarctation of the aorta and
      patent ductus arteriosus.
AB  - OBJECTIVE: To report clinical and procedural characteristics of twelve patients
      who received a covered stent for the treatment of aortic coarctation and
      concurrent patent ductus arteriosus (PDA). METHODS: A single center database was
      retrospectively evaluated to obtain data of patients with combined aortic
      coarctation and PDA. We selected patients in whom a covered stent was used for
      the treatment of both pathologies. The stent length was chosen so as to cover the
      entire length of the lesion from healthy to healthy tissue and also cover the
      ampulla of PDA. RESULTS: The median age of the patients was 15 (range, 6.5-35)
      years. The diameter of the coarctated segment increased from a median of 8.4
      (range, 2.6-10.8) mm to 16 (range, 9-24) mm (p<0.005), whereas the pressure
      gradient decreased from a median of 43 (range, 10-71) mm Hg to 0 (range, 0-8) mm
      Hg (p<0.005). Fourteen covered stents were used for 12 patients. Following
      deployment, seven stents were flared with larger and low-pressure balloons
      because of the gap between the distal end of the stent and the poststenotic
      dilated segment of the aorta, which caused residual PDA shunts and/or instability
      of the stent. After the procedure, no residual PDA shunt was present in any
      patient. CONCLUSION: To the best of our knowledge, this study includes the
      largest series of patients reported in literature in whom covered CP stents were
      used for simultaneous percutaneous treatment of coarctation and PDA. The
      procedure was successful and stable results were obtained during follow-up in all
      cases.

PMID- 29578199
TI  - Initial treatment dropout in patients with substance use disorders attending a
      tertiary care de-addiction centre in north India.
AB  - Background & objectives: Dropout from substance use disorders treatment is
      associated with poor outcomes. Although many factors have been associated with an
      early dropout of patients, the reasons for dropping out of treatment prematurely
      remain poorly understood particularly in the Indian context. This study was aimed
      to study socio-demographic and clinical variables predicting initial dropout of
      patients attending a tertiary care de-addiction treatment centre in north India.
      Methods: Information was extracted from the records of consecutive newly
      registered patients from January 2011 to December 2014. The patients who did not
      come for follow up within 30 days of the first contact were defined as initial
      dropouts. Results: Data of 7991 patients could be retrieved. Majority of the
      sample consisted of male, married and employed individuals. Of them, 4907
      patients (61.3%) were considered initial dropouts. Multivariate analysis revealed
      that after controlling for other factors, greater age, being employed, lower
      educational status, lesser duration of substance use, use of alcohol, opiate,
      tobacco, cannabis or sedative-hypnotic use but the absence of multi-substance use
      predicted initial drop out. Interpretation & conclusions: This study identified
      some socio-demographic and clinical variables which might predict treatment
      attrition in substance use disorders. Clinician's awareness towards these factors
      and tailor-made intervention might improve initial treatment retention. Future
      research could be directed to find the validity of this assumption.

PMID- 29578202
TI  - The impact of the left ventricular pacing polarity and localization during
      cardiac resynchronization therapy on depolarization and repolarization
      parameters.
AB  - OBJECTIVE: Reversal of myocardial activation sequence during cardiac
      resynchronization therapy (CRT) may increase the transmural dispersion of
      repolarization (TDR), which may lead to ventricular arrhythmias. Quadripolar left
      ventricular (LV) leads offer 10 different pacing configurations. However, little
      is known about the role of pacing polarity on repolarization patterns. Our study
      aimed to investigate the impact of LV pacing polarity on depolarization and
      repolarization parameters in the same substrate in the same patient group.
      METHODS: This study prospectively analyzed 20 patients who were consecutively
      admitted and underwent CRT-D implantation with quadripolar LV leads. Two bipolar
      pacing vectors and two unipolar vectors, also called extended bipolar pacing
      vectors, from the same pacing sites were selected for comparison.
      Electrocardiogram markers of depolarization and repolarization were measured and
      compared. RESULTS: Bipolar LV pacing was associated with a significantly shorter
      QRS duration (basal, unipolar vs. bipolar, 135.1+/-17.8 vs. 119.3+/-14.5, p<0.01;
      non-basal, unipolar vs. bipolar, 134.4+/-15.7 vs. 121.9+/-10.3, p<0.01) and Tp-Te
      value (Basal, unipolar vs. bipolar, 119.1+/-36.7 vs. 97.6+/-27.9, p<0.05; non
      basal, unipolar vs. bipolar, 117.9+/-36.3 vs. 98.6+/-20.4, p<0.05) than those in
      unipolar pacing. LV pacing from basal and non-basal segments had no differential
      effect on the repolarization parameters. CONCLUSION: The LV pacing polarity
      significantly affects QRS duration but not repolarization patterns regardless of
      the pacing site in the same substrate. From the perspective of basal and non
      basal segments, the LV pacing site has no differential effect on the
      repolarization parameters.

PMID- 29578203
TI  - Coronary angiography using the left distal radial approach - An alternative site
      to conventional radial coronary angiography.
AB  - OBJECTIVE: To share our experience with the left distal radial approach for
      transradial coronary angiography and interventions. By performing the radial
      puncture in the fossa radialis or the so called anatomical "Snuffbox" we aimed to
      present the feasibility and complications of this new technique. METHODS: Left
      distal radial artery was used as an access site in 54 patients admitted to our
      clinic for coronary angiography and intervention between May 25th and October
      20th 2017. All of them had pulse in their left distal radial artery. In the
      laboratory, they had their left arm gently flexed at the shoulder so that the
      hand was placed over their right groin. The operator stood on the right side of
      the patient and performed coronary angiography and interventions. During the
      hospital stay, demographic features and complications were recorded. RESULTS:
      Mean age of patients was 59.3 years and 80% were male. We used Judkins 6 French
      catheters for the procedures. Seventeen patients admitted with acute coronary
      syndrome. They all underwent successful left distal transradial coronary
      angiography and intervention. Primary angioplasty was performed in 10 patients.
      In total, 20 patients had coronary intervention. Left anterior descending artery
      was the artery requiring most intervention (11 patients). Two patients
      experienced brachial spasm requiring crossover to right femoral artery. There
      were no cases of radial artery occlusion, hematoma, or hand numbness. The radial
      sheath was removed at procedure termination. Hemostasis was achieved with manual
      compression. CONCLUSION: Left distal radial approach is safe and feasible as a
      new technique for coronary angiography and interventions.

PMID- 29578204
TI  - Differences in gene expression related to the outcomes of obesity treatment, peak
      oxygen uptake, and fatty acid metabolism measured in a cardiopulmonary exercise
      test.
AB  - INTRODUCTION The obesity pandemic requires development of methods that could be
      used on a large scale, such as the cardiopulmonary exercise test (CPET). Gene
      expression may explain CPET results on the molecular level. OBJECTIVES The aim of
      this study was to compare gene expression in obesity, depending on CPET results.
      PATIENTS AND METHODS The study group consisted of 9 obese patients and 7
      controls. The treatment encompassed diet, rehabilitation, and behavioral therapy.
      Diet was based on the body composition analyzed by bioelectrical impedance,
      resting metabolic rate, and subjective patient preferences. The rehabilitation
      depended on the CPET results: maximal oxygen uptake and fatty acid metabolism.
      Behavioral intervention focused on the diagnosis of health problems leading to
      obesity, lifestyle modification, training in self-assessment, and development of
      healthy habits. The intensive treatment lasted for 12 weeks and consisted of
      consultations with a physician, dietitian, and medical rehabilitation specialist.
      RNA was isolated from the whole blood. A total of 47 323 transcripts were
      analyzed, of which 32 379 entities were confirmed to have high quality of RNA.
      RESULTS We observed differences in gene expression related to the CPET results
      indicating abnormalities in fat oxidation and maximal oxygen uptake. The genes
      with major differences in expression were: CLEC12A, HLA-DRB1, HLA-DRB4, HLA
      A29.1, IFIT1, and LOC100133662. CONCLUSIONS The differences in gene expression
      may account for the outcomes of treatment related to inflammation caused by
      obesity, which affects the muscles, fat tissue, and fatty acid metabolism.

PMID- 29578205
TI  - Publisher Correction: Wave energy budget analysis in the Earth's radiation belts
      uncovers a missing energy.
AB  - This corrects the article DOI: 10.1038/ncomms8143.

PMID- 29578206
TI  - Publisher Correction: Is wave-particle objectivity compatible with determinism
      and locality?
AB  - This corrects the article DOI: 10.1038/ncomms5997.

PMID- 29578210
TI  - Metabolism: High salt intake as a driver of obesity.

PMID- 29578209
TI  - Epidemiology: Chronic disease, cancer, and exercise - a common link.

PMID- 29578208
TI  - Angiotensin-converting enzyme in innate and adaptive immunity.
AB  - Angiotensin-converting enzyme (ACE) - a zinc-dependent dicarboxypeptidase with
      two catalytic domains - plays a major part in blood pressure regulation by
      converting angiotensin I to angiotensin II. However, ACE cleaves many peptides
      besides angiotensin I and thereby affects diverse physiological functions,
      including renal development and male reproduction. In addition, ACE has a role in
      both innate and adaptive responses by modulating macrophage and neutrophil
      function - effects that are magnified when these cells overexpress ACE.
      Macrophages that overexpress ACE are more effective against tumours and
      infections. Neutrophils that overexpress ACE have an increased production of
      superoxide, which increases their ability to kill bacteria. These effects are due
      to increased ACE activity but are independent of angiotensin II. ACE also affects
      the display of major histocompatibility complex (MHC) class I and MHC class II
      peptides, potentially by enzymatically trimming these peptides. Understanding how
      ACE expression and activity affect myeloid cells may hold great promise for
      therapeutic manipulation, including the treatment of both infection and
      malignancy.

PMID- 29578207
TI  - Use of oral anticoagulants in patients with atrial fibrillation and renal
      dysfunction.
AB  - Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly
      prevalent in the general population and share common risk factors such as older
      age, hypertension and diabetes mellitus. The presence of CKD increases the risk
      of incident AF, and, likewise, AF increases the risk of CKD development and/or
      progression. Both conditions are associated with substantial thromboembolic risk,
      but patients with advanced CKD also exhibit a paradoxical increase in bleeding
      risk. In the landmark randomized clinical trials that compared non-vitamin K
      antagonist oral anticoagulants (NOACs) with warfarin for thromboprophylaxis in
      patients with AF, the efficacy and safety of NOACs in patients with mild-to
      moderate CKD were similar to those in patients without CKD. Dose adjustment of
      NOACs as per the prescribing label is required in this population. Owing to
      limited trial data, evidence-based recommendations for the management of patients
      with AF and severe CKD or end-stage renal disease on dialysis are lacking.
      Observational cohort studies have reported conflicting results, and the
      management of these particularly vulnerable patients remains challenging and
      requires careful assessment of stroke and bleeding risk and, where appropriate,
      use of warfarin with good-quality anticoagulation control.

PMID- 29578211
TI  - DECLINING PREVALENCE OF HIV AND OTHER SEXUALLY TRANSMITTED INFECTIONS AMONG
      FEMALE SEX WORKERS IN JOS, NORTH-CENTRAL NIGERIA.
AB  - BACKGROUND: Female Sex Workers (FSWs) are key reservoirs of human
      immunodeficiency virus (HIV) and other sexually transmitted infections (STIs)
      from which transmission to the general population fuels epidemics. STIs amplify
      HIV infectiousness and susceptibility. We determined the status of HIV and STIs
      among brothel-based FSWs in Jos as part of an ongoing prevention intervention.
      METHOD: Between January and May 2012, consenting consecutive brothel-based FSWs
      were recruited from previously designated brothels across Jos. HIV counseling and
      testing as well as screening for gonorrhoea, syphilis, trichomonasis, candidasis
      and Bacteria vaginosis (BV) were performed. Positive cases were provided free
      treatment and follow-up at Solat Women Hospital, Jos. Ethical clearance was
      obtained from Jos University Teaching Hospital (JUTH) ethical committee. RESULT:
      Two hundred FSWs aged 27.6 +/- 4.6 years (range 15-55 years) were recruited and
      of these, 47 (23.5%) were HIV Positive, 20 (10.0%) had syphilis, 9 (4.5%) had
      Neisseria gonorrhea, 3 (1.5%) had Trichomonas vaginalis and 86 (43.0%) had BV.
      The association between HIV and bacterial vaginosis was statistically significant
      (OR of 2.2, 95% CI of 1.1-4.2, P-value=0.02). In comparison to similar prevalence
      in 2006, the current findings represent 51.5% decline in HIV prevalence, 40.8%
      decline for syphilis and over 83.3% decline in prevalence for Trichomonas
      vaginalis. There was no significant change in the prevalence of Neisseria
      gonorrhoea and BV. CONCLUSION: The prevalence of HIV and STIs among brothel-based
      FSWs in Jos remain unacceptably high, although, there is a declining trend. A
      comprehensive HIV prevention program targeting these women is required to block
      transmission to the general population.

PMID- 29578212
TI  - Emerging chemical strategies for imprinting magnetism in graphene and related 2D
      materials for spintronic and biomedical applications.
AB  - Graphene, a single two-dimensional sheet of carbon atoms with an arrangement
      mimicking the honeycomb hexagonal architecture, has captured immense interest of
      the scientific community since its isolation in 2004. Besides its extraordinarily
      high electrical conductivity and surface area, graphene shows a long spin
      lifetime and limited hyperfine interactions, which favors its potential
      exploitation in spintronic and biomedical applications, provided it can be made
      magnetic. However, pristine graphene is diamagnetic in nature due to solely sp2
      hybridization. Thus, various attempts have been proposed to imprint magnetic
      features into graphene. The present review focuses on a systematic classification
      and physicochemical description of approaches leading to equip graphene with
      magnetic properties. These include introduction of point and line defects into
      graphene lattices, spatial confinement and edge engineering, doping of graphene
      lattice with foreign atoms, and sp3 functionalization. Each magnetism-imprinting
      strategy is discussed in detail including identification of roles of various
      internal and external parameters in the induced magnetic regimes, with assessment
      of their robustness. Moreover, emergence of magnetism in graphene analogues and
      related 2D materials such as transition metal dichalcogenides, metal halides,
      metal dinitrides, MXenes, hexagonal boron nitride, and other organic compounds is
      also reviewed. Since the magnetic features of graphene can be readily masked by
      the presence of magnetic residues from synthesis itself or sample handling, the
      issue of magnetic impurities and correct data interpretations is also addressed.
      Finally, current problems and challenges in magnetism of graphene and related 2D
      materials and future potential applications are also highlighted.

PMID- 29578213
TI  - Folate decorated hollow spheres of microporous organic networks as drug delivery
      materials.
AB  - Hollow and microporous organic network spheres decorated with folic acids (H-MON
      FA) were prepared using silica templates by the Sonogashira coupling of organic
      building blocks and successive post-synthetic modifications. The drug (DOX)
      delivery performance of H-MON-FA to cancer cells was studied.

PMID- 29578214
TI  - Correction: Jadomycins, put a bigger ring in it: isolation of seven- to ten
      membered ring analogues.
AB  - Correction for 'Jadomycins, put a bigger ring in it: isolation of seven- to ten
      membered ring analogues' by Camilo F. Martinez-Farina et al., Chem. Commun.,
      2015, 51, 14617-14619.

PMID- 29578216
TI  - Chloroplast-containing coacervate micro-droplets as a step towards
      photosynthetically active membrane-free protocells.
AB  - Encapsulation of structurally and functionally intact chloroplasts within
      coacervate micro-droplets is used to prepare membrane-free protocells capable of
      light-induced electron transport.

PMID- 29578215
TI  - alpha-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence
      imaging guided photothermal therapy/chemotherapy of breast cancer.
AB  - Micellar nanoparticles have unique advantages as carriers for therapeutic or
      imaging agents, owing to their smaller size and better penetration of tumors.
      However, some agents, due to their physical or chemical properties, are difficult
      to load into micelles. IR780 is one of these agents, and is also a promising near
      infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer
      photothermal therapy (PTT). Its hydrophobic and high crystallization structure
      results in limited bioavailability in vivo. It is difficult to load into micelles
      constructed from an amphiphilic block polymer with relatively low molecular
      weight. In this study, we use computer simulation and introduce another small
      biomolecule, alpha-lipoic acid, into the micelles constructed from a mPEG-PCL
      copolymer, to lower the energy of molecular interaction between MPEG-PCL and
      IR780, and expect to enhance the loading capacity of the micelles to IR780. The
      introduction of alpha-lipoic acid decreases the energy of molecular interaction
      between MEPG-PCL and IR780 from -46.18 kJ mol-1 to -196.52 kJ mol-1 and increases
      the loading capacity and stability of the mPEG-PCL micelles to IR780, which also
      maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded
      mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of
      cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the
      DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further
      evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast
      cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve
      as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

PMID- 29578217
TI  - Real-space evidence of Watson-Crick and Hoogsteen adenine-uracil base pairs on
      Au(111).
AB  - From the interplay of high-resolution scanning tunneling microscopy imaging and
      density functional theory calculations, we show the real-space evidence of the
      formation of Watson-Crick and Hoogsteen adenine-uracil base pairs on an Au(111)
      surface with the employment of base derivatives, and further investigate the
      relative stability of the two types of adenine-uracil base pairs.

PMID- 29578218
TI  - Correction: Encoding matter with regiospecific 12C/13C isotopic labels.
AB  - Correction for 'Encoding matter with regiospecific 12C/13C isotopic labels' by
      James J. La Clair et al., Chem. Commun., 2018, 54, 2611-2614.

PMID- 29578219
TI  - Palladium-catalyzed dehydrogenative coupling of cyclic enones with thiophenes: a
      rapid access to beta-heteroarylated cyclic enones.
AB  - Dehydrogenative coupling of cyclic enones with heteroarenes has been a
      longstanding challenge because of the competitive ketone dehydrogenation and
      conjugated addition. Herein, a dehydrogenative coupling reaction of cyclic enones
      of different sizes with substituted thiophenes to construct beta-thienyl cyclic
      enone compounds through palladium-catalyzed C-H functionalization under mild
      reaction conditions is reported. Simple substituted thiophenes with different
      functional groups can be directly introduced into cyclic enones with predominant
      regioselectivity at the alpha position of thiophene moieties and excellent
      functional group tolerance. Further molecular transformations of the coupling
      products to synthetically useful meta-heteroarylated phenol derivatives have also
      been demonstrated.

PMID- 29578220
TI  - Unraveling the effects of amino acid substitutions enhancing lipase resistance to
      an ionic liquid: a molecular dynamics study.
AB  - Understanding of the structural and dynamic properties of enzymes in non-aqueous
      media (e.g., ionic liquids, ILs) is highly attractive for protein engineers and
      synthetic biochemists. Despite a growing number of molecular dynamics (MD)
      simulation studies on the influence of different ILs on wild-type enzymes, the
      effects of various amino acid substitutions on the stability and activity of
      enzymes in ILs remain to be unraveled at the molecular level. Herein, we selected
      fifty previously reported Bacillus subtilis lipase A (BSLA) variants with
      increased resistance towards an IL (15 vol% 1-butyl-3-methylimidazolium
      trifluoromethanesulfonate; [Bmim][TfO]), and also ten non-resistant BSLA variants
      for a MD simulation study to identify the underlying molecular principles. Some
      important properties differentiating resistant and non-resistant BSLA variants
      from wild-type were elucidated. Results show that, in 15 vol% [Bmim][TfO] aqueous
      solution, 40% and 60% of non-resistant variants have lower and equal
      probabilities to form a catalytically important hydrogen bond between S77 and
      H156 compared to wild-type, whereas 36% and 56% of resistant variants show
      increased and equal probabilities, respectively. Introducing positively charged
      amino acids close to the substrate-binding cleft for instance I12R is beneficial
      for the BSLA resistance towards 15 vol% [Bmim][TfO], likely due to the reduced
      probability of [Bmim]+ cations clustering near the cleft. In contrast,
      substitution with a large hydrophobic residue like I12F can block the cleft
      through hydrophobic interaction with a neighboring nonpolar loop 134-137 or/and
      an attractive pi-pi interaction with [Bmim]+ cations. In addition, the resistant
      variants having polar substitutions on the surface show higher ability to
      stabilize the surface water molecule network in comparison to non-resistant
      variants. This study can guide experimentalists to rationally design promising IL
      resistant enzymes, and contribute to a deeper understanding of protein-IL
      interactions at the molecular level.

PMID- 29578221
TI  - Packing of metalized polymer nanofibers for aneurysm embolization.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is the extravasation of blood into the
      subarachnoid space and is fatal in most cases. Platinum coils have been used to
      fill the hemorrhage site and prevent the extravasation of blood. Here we explored
      the use of Pt-coated polymer nanofibers (NF) to prevent blood extravasation and
      were able to achieve improved results in vitro. The polymer nanofibers were
      produced via electrospinning and were subsequently electroplated with Pt,
      resulting in metalized nanofibers. These nanofibers were installed within a
      microfluidic channel, and the resulting reduction in the permeability was
      evaluated using a fluid similar to blood. Based on the obtained results, these
      newly developed nanofibers are expected to decrease the operation cost for SAH,
      owing to their reduced size and low material cost. Furthermore, it is expected
      that these nanofibers will be used in a smaller amount during SAH operation while
      having the same preventive effect. This should reduce the operational risk
      associated with the multiple steps required to place the Pt coils at the SAH
      site. Finally, the underlying hydrodynamic mechanism responsible for the reduced
      permeability of the synthesized nanofibers is described.

PMID- 29578222
TI  - Water soluble compounds of Rosmarinus officinalis L. improve the oxidative and
      inflammatory states of rats with adjuvant-induced arthritis.
AB  - Anti-inflammatory and antioxidant properties have been attributed to constituents
      of Rosmarinus officinalis. Considering the inflammatory nature of arthritis and
      the oxidative stress induced by the disease, this work aimed to investigate if R.
      officinalis is able to attenuate oxidative and inflammatory injuries caused by
      the disease. Rats with complete Freund's adjuvant induced arthritis were used. An
      aqueous extract of the rosemary leaves was administered orally. The parameters
      related to oxidative stress were measured in the liver, brain and plasma. The
      administration of the rosemary extract (RE) to arthritic rats diminished
      oxidative damage (e.g., less carbonylated proteins), improved the oxidative state
      (e.g., less reactive oxygen species) and also increased the antioxidant capacity
      by increasing the GSH level and the GSH/GSSG ratio and by almost normalizing the
      activity of several antioxidant enzymes. The treatment of arthritic rats with the
      extract also diminished paw edema, the number of leukocytes recruited in the
      femoro-tibial joint cavities and the weight of the lymph nodes and delayed the
      appearance of secondary lesions. Twelve phenolic compounds were identified and
      quantified in the aqueous RE, rosmarinic acid being the most abundant one. In
      addition, the extract also contains polysaccharides and proteins. The anti
      inflammatory and antioxidant activities of the RE can be attributed, partly at
      least, to its content of polyphenolics with the strong possibility of synergistic
      interactions as well as metabolic activations. The results corroborate and
      amplify the general notion that rosemary aqueous extracts possess efficient anti
      inflammatory agents and suggest that they are able to attenuate the oxidative
      stress inherent to arthritis.

PMID- 29578223
TI  - Fluorescence and photoacoustic dual-mode imaging of tumor-related mRNA with a
      covalent linkage-based DNA nanoprobe.
AB  - We developed a dual-mode DNA nanoprobe based on covalent linkage for fluorescence
      imaging and photoacoustic imaging of tumor-related mRNA.

PMID- 29578224
TI  - Combining gold nanoparticle antennas with single-molecule fluorescence resonance
      energy transfer (smFRET) to study DNA hairpin dynamics.
AB  - The association of a plasmonic nano-antenna with single-molecule FRET technique
      presents new prospects to investigate the dynamics of biological molecules.
      However, the presence of a plasmonic nano-antenna significantly modifies the FRET
      rate and efficiency; this makes its applicability to the prevalent single
      molecule FRET experiments unclear. Herein, using gold nanoparticle antennas of
      different sizes and DNA hairpins labelled with FRET pairs (Cy3 and Cy5) as the
      model system, we performed experiments to study the folding dynamics of single
      DNA hairpins at various salt concentrations. Our results indicate that gold
      nanoparticle antennas can enhance single-molecule fluorescence of Cy3 and Cy5 up
      to 3-5 folds, substantially reduce the FRET efficiency, and alter the obtained
      FRET efficiency histograms. However, the folding dynamics of DNA hairpins remains
      unaffected, and the correct kinetic and dynamic information can still be
      extracted from the seriously modified FRET efficiencies. Therefore, our
      experiments demonstrate the feasibility and compatibility for applying plasmonic
      nano-antennas to the mostly used single-molecule FRET assays, which provide a
      broad range of possibilities for the future applications of these nano-antennas
      in studying various essential biological processes.

PMID- 29578225
TI  - Two-dimensional transition metal dichalcogenides as metal sources of metal
      organic frameworks.
AB  - By taking advantage of the layered structure and decent M-X bond strength of
      transition metal dichalcogenides (TMDCs), herein versatile Ti-MOFs were
      successfully prepared with layered titanium disulfide (TiS2) as the titanium
      source. In addition, the phase evolution mechanism, CO2 adsorption capacity and
      photocatalytic degradation performance of the prepared Ti-MOFs were investigated
      in detail.

PMID- 29578226
TI  - Site-selective bond scission of methylbenzoate following core excitation.
AB  - The chemical bond scission of methylbenzoate (C6H5CO2CH3) following core
      excitation at the C and O K edges was examined from partial ion yield
      measurements across these edges using synchrotron radiation. Site-specific
      scission of the C-O bonds was observed at both edges. Theoretical X-ray
      absorption spectra (XAS) were obtained using density functional theory. Peak
      assignments in the observed spectra were found to be consistent with the theory.
      From core-excited state dynamics calculations, an elongation of the C-O bond was
      predicted and provides an explanation of the observed partial ion yield
      enhancement of CH3+ and C6H5CO+ at the core-excited resonances at both edges.

PMID- 29578227
TI  - Upconversion thermometry: a new tool to measure the thermal resistance of
      nanoparticles.
AB  - The rapid evolution in luminescence thermometry in the last few years gradually
      shifted the research from the fabrication of more sensitive nanoarchitectures
      towards the use of the technique as a tool for thermal bioimaging and for the
      unveiling of properties of the thermometers themselves and of their local
      surroundings, for example to evaluate heat transport at unprecedented small
      scales. In this work, we demonstrated that KLu(WO4)2:Ho3+,Tm3+ nanoparticles are
      able to combine controllable heat release and upconversion thermometry permitting
      to estimate its thermal resistance (in air), a key parameter to model the heat
      transfer at the nanoscale.

PMID- 29578228
TI  - An organic-inorganic hybrid zinc phosphite framework with room temperature
      phosphorescence.
AB  - A novel room temperature phosphorescent material has been developed by the use of
      luminescent organic rigid poly-imidazole moieties coordinating to a zinc
      phosphite framework, which shows excellent thermal and mechanical stability.

PMID- 29578229
TI  - Three-dimensional iron(ii) porous coordination polymer exhibiting carbon dioxide
      dependent spin crossover.
AB  - We report a three-dimensional Fe(ii) porous coordination polymer that exhibits a
      spin crossover temperature change following CO2 sorption (though not N2
      sorption). Furthermore, single crystals of the desolvated polymer with CO2
      molecules at three different temperatures were characterised by X-ray
      crystallography.

PMID- 29578230
TI  - A symmetrical ionic liquid/Li salt system for rapid ion transport and stable
      lithium electrochemistry.
AB  - Contrary to the accepted wisdom that avoids cation symmetry for the sake of
      optimum electrolyte properties, we reveal outstanding behaviour for the
      diethylpyrrolidinium cation ([C2epyr]), in combination with the
      bis(fluorosulfonyl)imide (FSI) anion and Li[FSI]. The equimolar
      [C2epyr][Li][FSI]2 is a liquid with high conductivity, high Li transference
      number and >90% lithium metal cycling efficiency. The high level of performance
      for these electrolytes invites consideration of a new class of electrolytes for
      lithium batteries.

PMID- 29578231
TI  - Connectivity-driven bi-thermoelectricity in heteroatom-substituted molecular
      junctions.
AB  - To improve the thermoelectric performance of molecular junctions formed by
      polyaromatic hydrocarbon (PAH) cores, we present a new strategy for enhancing
      their Seebeck coefficient by utilizing connectivities with destructive quantum
      interference combined with heteroatom substitution. Starting from the parent PAH,
      with a vanishing mid-gap Seebeck coefficient, we demonstrate that the
      corresponding daughter molecule obtained after heteroatom substitution possesses
      a non-zero, mid-gap Seebeck coefficient. For the first time, we demonstrate a "bi
      thermoelectric" property, where for a given heteroatom and parent PAH, the sign
      of the mid-gap Seebeck coefficient depends on connectivity and therefore the
      daughter can exhibit both positive and negative Seebeck coefficients. This bi
      thermoelectric property is important for the design of tandem thermoelectric
      devices, where materials with both positive and negative Seebeck coefficients are
      utilized to boost the thermovoltage. Simple parameter-free rules for predicting
      the Seebeck coefficient of such molecules are presented, which form a powerful
      tool for designing efficient molecular thermoelectric devices.

PMID- 29578232
TI  - Crumpled graphene ball-based broadband solar absorbers.
AB  - Sheet-like graphene tends to stack with each other in thin films, resulting in
      relatively smooth microstructures with increased reflection as the thickness
      increases. In contrast, when the sheets are crumpled into a shape like paper
      balls, reflection is greatly reduced. In this work, crumpled graphene balls are
      found to be strong light absorbers in the visible and near-infrared regions.
      Average absorption of thin films made of crumpled graphene balls can reach up to
      97.4% in the wavelength region of 350-2500 nm. When crumpled graphene balls are
      used as the solar absorber for the interfacial evaporation system, an evaporation
      efficiency of 84.6% was obtained under one sun at ambient pressure. Enhanced
      solar absorption of crumpled graphene balls, coupled with their aggregation
      resistance and universal solution processability, makes them promising candidates
      for solar heating/distillation applications.

PMID- 29578233
TI  - Tuning the surface of Au nanoparticles using poly(ethylene glycol)-block
      poly(propylene glycol)-block-poly(ethylene glycol): enzyme free and label free
      sugar sensing in serum samples using resonance Rayleigh scattering spectroscopy.
AB  - Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (F
      108) functionalized gold nanoparticles (Au NPs) have been successfully
      synthesized. During synthesis it is found that an increase in the F-108
      concentration contributes to agglomeration in the media, increasing the size of
      the Au particles, and boosting the curcumin concentration leads to a higher
      density of functional groups, resulting in smaller Au NPs. FT-IR analysis reveals
      that the hydroxyl and phenolic groups of curcumin and F-108 are involved during
      the functionalization of Au surfaces. Enhancement in the fluorescence/RRS
      intensity is due to the combination of the influence of the shape/size of the Au
      NPs as well as the extent of curcumin conjugation at the interface of the Au NP
      surface and F-108. The presence of sugar molecules remarkably boosts the RRS
      intensity without significantly affecting the fluorescence and surface plasmon
      absorbance of the Au NPs; in contrast, the RRS intensity of standard CTAB
      functionalized Au NPs is unaffected by glucose molecules indicating that the
      functionalization of F-108 at Au surfaces is crucial. Interestingly, no
      interference from other potential interferents and antioxidant substances like
      ascorbic acid, creatinine and acetaminophen is observed. This method is simple
      and fast, and offers a wider linear dynamic range, 0-10 mM, that is applicable
      under physiological conditions and in serum samples. It is stable and provides an
      excellent recovery for serum samples, thus, potentially it can be useful in this
      field due to its low energy consumption, enzyme free assay, fast response time,
      better selectivity and sensitivity.

PMID- 29578234
TI  - Cardiac myoglobin participates in the metabolic pathway of selenium in rats.
AB  - As an essential micronutrient, selenium deficiency is a leading cause of
      cardiovascular diseases. The heart is continuously beating to deliver blood to
      the entire body, and this requires a high amount of energy. An adult heart
      normally obtains 50-70% of its adenosine 5'-triphosphate from fatty acid beta
      oxidation. An increase in fatty acid oxidation activity induces the generation of
      larger amounts of by-products (reactive oxygen species, ROS) from mitochondrial
      oxidative phosphorylation. Selenium-dependent glutathione peroxidases play a
      critical role in the removal of these ROS, especially organic hydroperoxides,
      from the heart. The definitive transport and/or detailed metabolic pathways from
      the selenium-source compounds to the selenoproteins in the heart still remain
      unclear. We explored the selenium-binding proteins in a rat cardiac cell lysate
      using its reactive metabolic intermediate, selenotrisulfide (STS), and MALDI TOF
      mass spectrometry. Several proteins with a free cysteine (Cys) thiol were found
      to be reactive with STS through a thiol-exchange reaction. The most distinctive
      Cys-containing protein in the cardiac cell lysate was identified as myoglobin
      (Mb) from a rat protein database search and tryptic fragmentation experiments.
      When separately examined in selenium adequate rats, selenium-binding to the
      cardiac Mb was verified using selenium-specific fluorometry. Cardiac Mb is
      thought to participate in the selenium metabolic pathway in the heart.

PMID- 29578235
TI  - Quantum spin Hall effect in two-dimensional hydrogenated SnPb alloy films.
AB  - Using first-principles calculations, we studied the geometric and band structures
      of 20 possible configurations of buckled hydrogenated SnPb alloy (SnxPb8-xH8)
      films. The configurations are topological insulators (TIs) when x >= 1. When x
      increases from 1 to 7, the band gap increases from 0.087 eV to 0.98 eV. The
      topological characteristics are suggested by s-pxy band inversion and confirmed
      by helical edge states, which are time-reversal symmetry protected. According to
      spin-orbit coupling (SOC) analysis results, we draw the conclusion that the Pb
      atoms have greater SOC strength than the Sn atoms, so when the number ratio of Pb
      and Sn atoms is greater than 1/12 the SOC strength is large enough to trigger the
      band inversion between the s and pxy orbitals, causing the SnPb alloy film to
      turn into a topological insulator (TI) from a normal band insulator (NI). We give
      a simple rule for the topological criterion of hydrogenated SnPb alloy films by
      comparing the ratio of Pb and Sn atoms. This would provide a useful reference for
      the design of topological devices based on NI-TI hetero-junctions for
      experiments.

PMID- 29578236
TI  - Clustering and assembly dynamics of a one-dimensional microphase former.
AB  - Both ordered and disordered microphases ubiquitously form in suspensions of
      particles that interact through competing short-range attraction and long-range
      repulsion (SALR). While ordered microphases are more appealing materials targets,
      understanding the rich structural and dynamical properties of their disordered
      counterparts is essential to controlling their mesoscale assembly. Here, we study
      the disordered regime of a one-dimensional (1D) SALR model, whose simplicity
      enables detailed analysis by transfer matrices and Monte Carlo simulations. We
      first characterize the signature of the clustering process on macroscopic
      observables, and then assess the equilibration dynamics of various simulation
      algorithms. We notably find that cluster moves markedly accelerate the mixing
      time, but that event chains are of limited help in the clustering regime. These
      insights will inspire further study of three-dimensional microphase formers.

PMID- 29578237
TI  - Nutritional supplements for patients being treated for active visceral
      leishmaniasis.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a disease caused by a parasite, which
      can lead to death if untreated. Poor nutritional status hastens the progression
      of VL infection, and VL worsens malnutrition status. Malnutrition is one of the
      poor prognostic factors identified for leishmaniasis. However, the effects of
      nutritional supplementation in people treated for VL are not known. OBJECTIVES:
      To assess the effects of oral nutritional supplements in people being treated
      with anti-leishmanial drug therapy for VL. SEARCH METHODS: We searched the
      Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE,
      Embase, LILACS, and two trial registers up to 12 September 2017. We checked
      conference proceedings and WHO consultative meeting reports, the reference lists
      of key documents and existing reviews, and contacted experts and nutritional
      supplement companies. SELECTION CRITERIA: Randomized controlled trials (RCTs),
      quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled
      trials (NRCTs) of any oral nutritional supplement, compared to no nutritional
      intervention, placebo, or dietary advice alone, in people being treated for VL.
      DATA COLLECTION AND ANALYSIS: Two review authors independently screened the
      literature search results for studies that met the inclusion criteria. We had
      planned for two review authors to independently extract data and assess the risk
      of bias of the included studies. We planned to follow the Cochrane standard
      methodological procedures for assessing risk of bias and analysing the data. MAIN
      RESULTS: We identified no eligible studies for this review, either completed or
      ongoing. AUTHORS' CONCLUSIONS: We found no studies, either completed or ongoing,
      that assessed the effects of oral nutritional supplements in people with VL who
      were being treated with anti-leishmanial drug therapy. Thus, we could not draw
      any conclusions on the impact of these interventions on primary cure of VL,
      definitive cure of VL, treatment completion, self-reported recovery from illness
      or resolution of symptoms, weight gain, increased skinfold thickness, other
      measures of lean or total mass, or growth in children.This absence of evidence
      should not be interpreted as evidence of no effect for nutritional supplements in
      people under VL treatment. It means that we did not identify research that
      fulfilled our review inclusion criteria.The effects of oral nutritional
      supplements in people with VL who are being treated with anti-leishmanial drug
      therapy have yet to be determined by rigorous experimental studies, such as
      cluster-randomized trials, that focus on outcomes relevant for patients.

PMID- 29578238
TI  - Development of the AAS Statement on "Suicide" and "Physician Aid in Dying".
AB  - In August 2017, the American Association of Suicidology board passed a statement
      titled "Suicide" is not the same as "Physician aid in dying," which was developed
      partly in response to the fact that aid in dying is now legal in a number of
      jurisdictions. In Phase 1, eight members of the AAS who had indicated interest in
      this issue were asked to independently draft such a statement; the convener
      consolidated these drafts and comments into an initial statement. In Phase 2,
      five additional experts who might be expected to object were asked for their
      independent input; the convener consolidated these with the previous draft. No
      one objected to the statement altogether; extensive copyediting and rewording
      suggestions focused primarily on issues of overlap between "suicide" and
      "physician aid in dying." The resulting document represents an effort to try to
      accommodate the basic concerns of all participants. The document does not speak
      for or against legalization of this practice, but it may have bearing on whether
      suicide prevention professionals have an obligation to try to prevent such deaths
      and whether they may serve as consultants for psychological or psychiatric
      evaluations as sometimes required under US state law.

PMID- 29578239
TI  - Prediction of Liquid Specific Heat Capacity of Food Lipids.
AB  - : Specific heat capacity (cp ) is a temperature dependent physical property of
      foods. Lipid-being a macromolecular component of food-provides some fraction of
      the food's overall heat capacity. Fats/oils are complex chemicals that are
      generally defined by carbon length and degree of unsaturation. The objective of
      this investigation was to use advanced specific heat capacity measurement to
      determine the effect of fatty acid chemical structure on specific heat capacity
      of food lipids. In this investigation, the specific heat capacity of a series of
      triacylglycerols were measured to quantify the influence of fatty acid
      composition on specific heat capacity based on two parameters; the -average
      carbon number (C) and the average number of double bonds (U). A prediction model
      for specific heat capacity of food lipids as a function of C, U and temperature
      (T) has been developed. A multiple linear regression to the three-parameter model
      (R2 = 0.87) provided a good fit to the experimental data. The prediction model
      was evaluated by comparison with previously published specific heat capacity
      values of vegetable oils. It was found that the model provided a 0.53% error,
      while three other models from the literature predicted cp values with 0.85% to
      1.83% average relative deviation from experimental data. The outcomes from this
      research confirm that the thermophysical properties of fat present in foods are
      directly related to the physical chemical properties. PRACTICAL APPLICATION: The
      specific heat capacity of food products is widely used in process design.
      Improvements of current models to predict specific heat capacity of food products
      will assist in the development of efficient processes and in the control of food
      quality and safety. Furthermore, the understanding of how changes in chemical
      structure of macromolecular components of foods effect thermophysical properties
      may begin to allude to models that are not just empirical, but represent portions
      of the differences in chemistry.

PMID- 29578240
TI  - Necrotic amplification loop in acute pancreatitis: pancreatic stellate cells and
      nitric oxide are important players in the development of the disease.

PMID- 29578241
TI  - Psychometric properties of the suffering assessment questionnaire in adults with
      chronic diseases or life-threatening illness.
AB  - BACKGROUND: Suffering has been considered by many authors to be a difficult
      concept to assess and measure, as it is subjective and unique. However, to guide
      the diagnosis and decision-making of healthcare professionals, it is important to
      develop an instrument that differentiates the different suffering dimensions,
      namely, intra- and interpersonal suffering, awareness of suffering and spiritual
      suffering. AIM: The aim of this study was thus to design and validate an
      instrument for the assessment of the dimensions of suffering in adult patients
      with chronic diseases or life-threatening illnesses. METHOD: A methodological
      study was developed. The data were collected from two self-help organisations and
      a palliative care unit. The theoretical model was tested using confirmatory
      factor analysis. The study sample consisted of 251 patients with chronic diseases
      or life-threatening illnesses. The Sense of Coherence Scale, the Spiritual
      Assessment Scale and the Suffering Assessment Questionnaire in Adults with
      Chronic Diseases or Life-Threatening Illness (SAQ) were applied to each
      participant and were later returned for analysis. RESULTS: An SAQ version with 12
      items showed adequate psychometric characteristics of validity and internal
      consistency after being adapted to a four-dimensional structure that assesses the
      four dimensions of suffering. CONCLUSION: The results of confirmatory analysis
      indicated a good model fit that suggested that the advocated theoretical model is
      plausible.

PMID- 29578243
TI  - Clusters of Suicidal Events Among Young People: Do Clusters from One Time Period
      Predict Later Clusters?
AB  - We sought to compare clusters of suicidal events between two different time
      periods and examine the extent to which earlier clusters predict later clusters.
      We included data on suicides and suicide attempts from New South Wales between
      July 2001 and June 2012 and Western Australia between January 2000 and December
      2011. Suicide attempts included admissions to hospital for deliberate self-harm
      and suicides were deaths due to deliberate self-harm. We combined data on
      suicides and suicide attempts and grouped them into two equal time periods. We
      detected clusters in each period using Poisson discrete scan statistics adjusted
      for socio-economic status. We estimated the predictive values of earlier clusters
      on later clusters. The results showed that clusters from earlier time period had
      a moderate power (36%) in predicting later clusters. During the later time
      period, some additional cluster areas (14%) were found and some earlier cluster
      areas subsided (64%). Historical clusters predict 36% of the subsequent clusters,
      which is probably not sufficient for targeting interventions. Our study
      highlights the need for other strategies to detect emerging clusters, for
      example, up-to-date data.

PMID- 29578242
TI  - Proanthocyanidin-Rich Grape Seed Extract Modulates Intestinal Microbiota in
      Ovariectomized Mice.
AB  - : Grape-seed extract (GSE) is rich in proanthocyanidins (polymers of flavan-3
      ols). GSE is well known to have various beneficial effects to health. The
      objective of this study was to examine the effect of dietary GSE on the
      intestinal microbiota in ovariectomized (OVX) mice as a model of menopause.
      Phylum-level analyses using 16S rRNA-targeted group-specific polymerase-chain
      reaction primers in fecal samples collected 8 weeks postoperatively from OVX mice
      revealed that the proportion of Firmicutes and Bacteroidetes populations became
      imbalanced as compared with that in sham-operated control mice. That is, the
      ratio of Firmicutes:Bacteroidetes populations in the OVX group were increased
      significantly. When OVX animals were given dietary GSE, the imbalanced proportion
      of Firmicutes and Bacteroidetes populations was normalized to that seen in
      control mice. In addition, the body weight of OVX animals measured at 6 weeks
      postoperatively was significantly higher than that in sham-operated control
      animals. Dietary GSE also prevented OVX animals from increasing body weight.
      Thus, we postulated that GSE can improve imbalanced populations of intestinal
      microbiota, leading to prevention of obesity under conditions of not only
      menopause but morbidity. PRACTICAL APPLICATION: The GSE has a great potential to
      be a functional food to improve dysbiosis in post-menopausal women.

PMID- 29578244
TI  - The Fallen.

PMID- 29578245
TI  - Genome-wide analysis of Glycine soja ubiquitin (UBQ) genes and functional
      analysis of GsUBQ10 in response to alkaline stress.
AB  - Ubiquitin is a highly conserved protein with multiple essential regulatory
      functions through the ubiquitin-proteasome system. Even though its functions in
      the ubiquitin-mediated protein degradation pathway are very well characterized,
      the function of ubiquitin genes in the regulation of the alkaline stress response
      is not fully established. In this study, we identified 12 potential UBQ genes in
      the Glycine soja genome, and analyzed their evolutionary relationship, conserved
      domains and promoter cis-elements. We also explored the expression profiles of G.
      soja UBQ genes under alkaline stress, based on the transcriptome sequencing. We
      found that the expression of GsUBQ10 was significantly induced by alkaline
      stress, and the function of GsUBQ10 was characterized by overexpression in
      transgenic alfalfa (Medicago sativa). Our results suggested that GsUBQ10
      transgenic lines significantly improved the alkaline tolerance in alfalfa. The
      GsUBQ10 transgenic lines showed lower relative membrane permeability, lower malon
      dialdehyde content and higher catalase activity than in the wild-type plants.
      This indicates that GsUBQ10 is involved in regulating the reactive oxygen species
      accumulation under alkaline stress. Taken together, we identified an ubiquitin
      gene GsUBQ10 from G. soja, which plays a positive role in responses to alkaline
      stress in alfalfa.

PMID- 29578246
TI  - Psychological Impairment as a Predictor of Suicide Ideation in Individuals with
      Anorexia Nervosa.
AB  - Anorexia nervosa (AN) is an eating disorder characterized by severe food
      restriction resulting in low body weight and an intense fear of gaining weight.
      This disorder has one of the highest suicide rates of any psychiatric illness;
      however, few studies have investigated prospective predictors of suicide ideation
      (SI) in this population. Quality-of-life impairment may be particularly relevant
      for understanding suicide risk in AN, given associations with SI in other
      psychiatric disorders and associations with chronicity and severity in AN. This
      study explored associations between eating disorder-related impairment and SI in
      individuals with AN (n = 113) who completed assessments at treatment discharge
      and 3, 6, and 12 months after discharge. Greater psychological impairment
      predicted future occurrence of SI controlling for age, depression, history of SI,
      and eating disorder variables. Associations were specific to psychological
      impairment as other domains of impairment did not predict SI over time. Findings
      highlight the potential importance of targeting interpersonal-psychological
      consequences of AN to decrease future suicide risk.

PMID- 29578247
TI  - Benzo[a]pyrene-decreased gap junctional intercellular communication via
      calcium/calmodulin signaling increases apoptosis in TM4 cells.
AB  - The mechanism of male reproductive toxicity induced by benzo[a]pyrene (BaP) is
      poorly understood. Gap junctional intercellular communication (GJIC) is known to
      play a critical role in maintaining spermatogenesis. The aim of the present study
      was to determine the toxic effects of BaP in Sertoli cells, and to explore the
      possibility and potential mechanisms of BaP-induced changes in the level of GJIC,
      and the relationship between GJIC and BaP-induced apoptosis. We treated mouse
      Sertoli cell lines (TM4) with different concentrations (0.1-100 MUm) of BaP for 1
      48 hours, and found that GJIC exhibited a dose- and time-dependent
      downregulation. Treatment with 10 MUm BaP increased apoptosis, intracellular Ca2+
      level ([Ca2+ ]i ) and calmodulin (CaM) protein expression, and decreased the
      protein level of connexin 43 (Cx43) (also known as gap junction alpha-1 protein
      [GJA1]) in TM4 cells. However, BaP had no effect on the phosphorylation of Cx43
      at Ser279/282, Ser255, Ser368 or Ser262. Downregulation of [Ca2+ ]i by BAPTA-AM
      significantly attenuated the BaP-induced GJIC suppression, Cx43 protein decrease
      and CaM protein increase. Interestingly, inhibition of CaM expression by W7
      partially recovered BaP-induced GJIC inhibition, but had no effect on BaP-induced
      Cx43 protein decrease. Pretreatment with the GJIC activator retinoic acid
      significantly mitigated BaP-induced apoptosis. In conclusion, these results
      suggest that BaP can decrease GJIC via Ca2+ /CaM signaling, and that BaP-induced
      GJIC suppression increases apoptosis in TM4 cells.

PMID- 29578248
TI  - Incidence and related factors for intraoperative failed spinal anaesthesia for
      lower limb arthroplasty.
AB  - BACKGROUND: Spinal anaesthesia is the preferred choice for total hip- and knee
      arthroplasty (THA/TKA), due to the claimed superior outcome profile, relative
      simple technique and without the need for advanced airway support. However,
      choosing and informing about spinal anaesthesia should also include the risk for
      intraoperative failed spinal anaesthesia with associated pain, discomfort and
      suboptimal settings for airway management. Small-scale studies suggest incidences
      from 1 to 17%; however, no multi-institutional large data exists on failed spinal
      incidence and related factors during THA/TKA, hindering evidence-based
      information and potential anaesthesia stratification. METHODS: In a sub-analysis,
      data from a prospective study on spinal anaesthesia for THA/TKA were examined for
      incidence of intraoperative conversion to general anaesthesia. Potential
      perioperative factors (age, gender, American Society of Anaesthesiologist (ASA)
      score, height, weight, BMI, procedure, bupivacaine dosage and duration of time
      from spinal administration until end of surgery) were analysed with logistic
      regression for relation to failed spinal anaesthesia. RESULTS: In all, 1451
      patients were included for analysis, whereof 57 (3.9%) had failed spinal
      anaesthesia. Spinal failure patients were significantly younger (61 vs. 67 years,
      P = 0.003), and operation time longer in the failed spinal group vs no-failure,
      respectively (133 vs. 89 min, P < 0.001). No significant differences were found
      with regard to bupivacaine volume, gender, ASA-score, height, weight, BMI or THA
      vs. TKA. CONCLUSION: Failed spinal anaesthesia for THA and TKA is a relatively
      frequent occurrence and identification of risk patients is not feasible. These
      results should be considered when choosing anaesthesia and included in the
      information to patients.

PMID- 29578249
TI  - Preoperative vitamin D deficiency increases the risk of postoperative cognitive
      dysfunction: a predefined exploratory sub-analysis.
AB  - BACKGROUND: Vitamin D is important for maintaining physiological functions
      including cognition and its deficiency is associated with the occurrence of
      cognitive impairment. This study was to explore the association between
      preoperative vitamin D status and the occurrence of postoperative cognitive
      dysfunction (POCD) in elderly patients undergoing major surgery. METHODS: This
      was a predefined exploratory sub-analysis of one-centre data from a randomized
      controlled trial. In all, 123 elderly (>= 65 years) patients who were scheduled
      to undergo major cancer surgery were recruited. Serum 25-hydroxyvitamin D
      concentration was measured before surgery. In total, 59 nonsurgical control
      subjects with comparable age and education level were also enrolled. A battery of
      neuropsychological tests was administered the day before and the 7th day after
      surgery in patients or at the same time interval in control subjects. POCD was
      diagnosed according to the ISPOCD1 definition. RESULTS: 71.5% (88/123) of elderly
      patients had vitamin D deficiency (serum 25-hydroxyvitamin D concentration < 12
      ng/ml) before surgery; 24.4% (30/123) of them developed cognitive dysfunction at
      1 week after surgery. After adjusting for confounding factors, high preoperative
      serum 25-hydroxyvitamine D concentration was related to a decreased risk of POCD
      (odds ratio [OR]: 0.829, 95% confidence interval [CI]: 0.708-0.971; P = 0.020),
      whereas preoperative vitamin D deficiency was associated with an increased risk
      of POCD (OR: 8.427, 95% CI: 1.595-44.511; P = 0.012). CONCLUSIONS: Vitamin D
      deficiency is prevalent in elderly patients undergoing major cancer surgery and
      increases the risk of early POCD development. Whether prophylactic vitamin D
      supplementation can reduce POCD in the elderly deserves further study.

PMID- 29578250
TI  - Vasopressin and nitroglycerin decrease portal and hepatic venous pressure and
      hepato-splanchnic blood flow.
AB  - BACKGROUND: Various methods are used to reduce venous blood pressure in the
      hepato-splanchnic circulation, and hence minimise blood loss during liver
      surgery. Previous studies show that combination of vasopressin and nitroglycerin
      reduces portal pressure and flow in patients with portal hypertension, and in
      this study we investigated this combination in patients with normal portal
      pressure. METHOD: In all, 13 patients were studied. Measurements were made twice
      to confirm baseline (C1 and BL), during vasopressin infusion 4.8 U/h (V), and
      during vasopressin infusion combined with nitroglycerin infusion (V + N). Portal
      venous pressure (PVP), hepatic venous pressure (HVP), central haemodynamics and
      arterial and venous blood gases were obtained at each measuring point, and portal
      (splanchnic) and hepato-splanchnic blood flow changes were calculated. RESULTS:
      Vasopressin alone did not affect PVP, whereas HVP increased slightly. In
      combination with nitroglycerin, PVP decreased from 10.1 +/- 1.6 to 8.9 +/- 1.3
      mmHg (P < 0.0001), and HVP decreased from 7.9 +/- 1.9 to 6.2 +/- 1.3 mmHg (P =
      0.001). Vasopressin reduced portal blood flow by 47 +/- 19% and hepatic venous
      flow by 11 +/- 18%, respectively. Addition of nitroglycerin further reduced
      portal- and hepatic flow by 55 +/- 13% and 30 +/- 13%, respectively. Vasopressin
      alone had minor effects on central haemodynamics, whereas addition of
      nitroglycerin reduced cardiac index (3.2 +/- 0.7 to 2.7 +/- 0.5; P < 0.0001). The
      arterial-portal vein lactate gradient was unaffected. CONCLUSION: The combination
      of vasopressin and nitroglycerin decreases portal pressure and hepato-splanchnic
      blood flow, and could be a potential treatment to reduce bleeding in liver
      resection surgery.

PMID- 29578251
TI  - Quantifying species recovery and conservation success to develop an IUCN Green
      List of Species.
AB  - Stopping declines in biodiversity is critically important, but it is only a first
      step toward achieving more ambitious conservation goals. The absence of an
      objective and practical definition of species recovery that is applicable across
      taxonomic groups leads to inconsistent targets in recovery plans and frustrates
      reporting and maximization of conservation impact. We devised a framework for
      comprehensively assessing species recovery and conservation success. We propose a
      definition of a fully recovered species that emphasizes viability, ecological
      functionality, and representation; and use counterfactual approaches to quantify
      degree of recovery. This allowed us to calculate a set of 4 conservation metrics
      that demonstrate impacts of conservation efforts to date (conservation legacy);
      identify dependence of a species on conservation actions (conservation
      dependence); quantify expected gains resulting from conservation action in the
      medium term (conservation gain); and specify requirements to achieve maximum
      plausible recovery over the long term (recovery potential). These metrics can
      incentivize the establishment and achievement of ambitious conservation targets.
      We illustrate their use by applying the framework to a vertebrate, an
      invertebrate, and a woody and an herbaceous plant. Our approach is a preliminary
      framework for an International Union for Conservation of Nature (IUCN) Green List
      of Species, which was mandated by a resolution of IUCN members in 2012. Although
      there are several challenges in applying our proposed framework to a wide range
      of species, we believe its further development, implementation, and integration
      with the IUCN Red List of Threatened Species will help catalyze a positive and
      ambitious vision for conservation that will drive sustained conservation action.

PMID- 29578253
TI  - Castleman's disease diagnosed on fine needle aspiration cytology: A
      multidisciplinary approach to diagnosis.

PMID- 29578252
TI  - Development of health-related quality of life and symptoms in patients with
      advanced cancer in Greenland.
AB  - A prospective national cohort study assessed the development of health-related
      quality of life (HRQoL) and symptoms in adult patients undergoing treatment and
      care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ-C30
      version 3.0 questionnaire monthly for 4 months. Changes over time and between
      group comparisons were examined. Of 58 patients included in the study, 47%
      completed the questionnaire four times. Functioning was generally high, and
      improved social functioning was observed after 1 and 2 months. The highest
      symptom score was for fatigue followed by pain and nausea/vomiting. A high score
      for financial problems remained unchanged during the entire period. Patients with
      higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than
      patients with income below the poverty line. After 1 month, reduction in pain
      intensity was observed for Nuuk citizens compared with non-Nuuk citizens (p =
      .05). After 2 months, non-Nuuk citizens reported improved social functioning
      compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk
      citizens was improved compared with non-Nuuk citizens (p = .05). An important
      clinical finding was that patients' needs for support are related to social
      status, and geographical factors should be taken into account when planning
      palliative care.

PMID- 29578254
TI  - Muscle function deterioration in patients with haemophilia: Prospective
      experience from Costa Rica.
AB  - INTRODUCTION: In haemophilia, recurrent joint bleeds are responsible for the
      development of chronic joint damage, because blood induces biochemical changes in
      joint structures. Joint degeneration is a long process, and structural damage is
      often preceded by joint dysfunction, which is represented by quantitative and
      qualitative changes in the contraction pattern of muscles around the joints.
      Muscle function in patients with haemophilia is still poorly investigated. AIM:
      The aim of this 2-year prospective study was to assess the changes in muscle
      function of lower limbs in a group of patients affected with haemophilia in San
      Jose, Costa Rica. METHODS: Muscle function of lower limbs was assessed by means
      of surface electromyography (sEMG) accomplished at study enrolment and after 2
      years of follow-up. Gluteus medius, vastus medialis, biceps femoris,
      gastrocnemius and tibialis anterior were examined. All patients underwent
      concurrent clinical examination using Haemophilia Joint Health Score (HJHS).
      RESULTS: Sixty patients aged 2-43 years with severe haemophilia underwent
      clinical and sEMG evaluation. Thirty-two patients (53%) had target joints. sEMG
      parameters were altered in all patients and were not correlated to the presence
      of target joints and/or an abnormal HJHS. Muscle function deterioration was
      observed after 2 years of follow-up despite an unmodified HJHS. CONCLUSIONS:
      Muscle function of lower limbs as detected by means of sEMG was impaired in
      patients with haemophilia irrespective of the presence of overt joint damage.
      sEMG is a simple and sensitive assessment tool able to detect muscle dysfunction
      and so favouring the implementation of early rehabilitation therapy.

PMID- 29578255
TI  - Partial pancreatic transdifferentiation of primary human hepatocytes in the
      livers of a humanised mouse model.
AB  - BACKGROUND: Gene therapy is one treatment that may ultimately cure type 1
      diabetes. We have previously shown that the introduction of furin-cleavable human
      insulin (INS-FUR) to the livers in several animal models of diabetes resulted in
      the reversal of diabetes and partial pancreatic transdifferentiation of liver
      cells. The present study investigated whether streptozotocin-diabetes could be
      reversed in FRG mice in which chimeric mouse-human livers can readily be
      established and, in addition, whether pancreatic transdifferentiation occurred in
      the engrafted human hepatocytes. METHODS: Engraftment of human hepatocytes was
      confirmed by measuring human albumin levels. Following delivery of the empty
      vector or the INS-FUR vector to diabetic FRG mice, mice were monitored for weight
      and blood glucose levels. Intraperitoneal glucose tolerance tests (IPGTTs) were
      performed. Expression levels of pancreatic hormones and transcription factors
      were determined by a reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. RESULTS: Diabetes was reversed for a period of 60 days
      (experimental endpoint) after transduction with INS-FUR. IPGTTs of the insulin
      transduced animals were not significantly different from nondiabetic animals.
      Immunofluorescence microscopy revealed the expression of human albumin and
      insulin in transduced liver samples. Quantitative RT-PCR showed expression of
      human and mouse endocrine hormones and beta-cell transcription factors,
      indicating partial pancreatic transdifferentiation of mouse and human
      hepatocytes. Nonfasting human C-peptide levels were significantly higher than
      mouse levels, suggesting that transdifferentiated human hepatocytes made a
      significant contribution to the reversal of diabetes. CONCLUSIONS: These data
      show that human hepatocytes can be induced to undergo partial pancreatic
      transdifferentiation in vivo, indicating that the technology holds promise for
      the treatment of type 1 diabetes.

PMID- 29578256
TI  - The nutrition impact symptoms (NIS) score detects malnutrition risk in patients
      admitted to nephrology wards.
AB  - BACKGROUND: Nutritional screening tools recommended for the general hospitalised
      population do not always adequately detect malnutrition risk in patients with
      kidney disease. The present study assessed the validity and reliability of the
      Nutrition Impact Symptoms (NIS) score as a nutrition screening tool for
      hospitalised inpatients prefer in nephrology wards. METHODS: Nutritional status
      was classified using Subjective Global Assessment (SGA). NIS scores were
      calculated from the total score of responses to questions assessing symptoms
      impacting upon nutritional status from the patient-generated SGA. Concurrent
      validity of NIS score was assessed using a receiver operating characteristic
      curve to predict malnutrition risk against SGA. Predictive validity was examined
      against length of hospital stay (LOS) and 30-day re-admission using Poisson and
      logistic regression, respectively. Inter-rater reliability of NIS scoring between
      assessors was determined using intraclass correlation. RESULTS: In 143 patients
      [90 males; mean (SD) age 57.8 (15.8) years], malnutrition prevalence was 38%
      (54/143) using SGA (rating B/C). Predicting malnutrition risk with an NIS score
      of >=3 had a sensitivity of 0.89 and a specificity of 0.65 (area under the curve
      = 0.81 [95% confidence interval (CI) = 0.74-0.88]). For each 1-point increase in
      NIS score, the model predicted a 1.9% rise in the risk of an increased LOS (P =
      0.002). Thirty-day re-admission was not associated with NIS score. Inter-rater
      reliability was moderate (mean difference = 0.53; intraclass correlation
      coefficient = 0.74; 95% CI = 0.57-0.85). CONCLUSIONS: Nutrition impact symptoms
      score is a valid stand-alone nutrition screening tool for identifying
      malnutrition risk in nephrology inpatients and is associated with LOS.

PMID- 29578257
TI  - An automated quantitative DNA image cytometry system detects abnormal cells in
      cervical cytology with high sensitivity.
AB  - OBJECTIVE: To evaluate the performance of an automated DNA-image-cytometry system
      as a tool to detect cervical carcinoma. METHODS: Of 384 liquid-based cervical
      cytology samples with available biopsy follow-up were analyzed by both the Imager
      System and a high-risk HPV test (Cobas). RESULTS: The sensitivity and specificity
      of Imager System for detecting biopsy proven high-grade squamous intraepithelial
      lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were
      89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but
      additional HPV 16/18 genotyping increased the specificity to 69.58%. The
      sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+)
      lesions among atypical squamous cells of undetermined significance samples were
      80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst
      the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical
      squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager
      System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and
      33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18
      genotyping increased the specificity to 19.05%. Among low-grade squamous
      intraepithelial lesion cases, the sensitivity and specificity of the Imager
      System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%,
      respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18
      genotyping increased the specificity to 79.76%. The overall results of imager and
      high-risk HPV test agreed in 69.43% (268) of all samples. CONCLUSIONS: The
      automated imager system and HPV 16/18 genotyping can enhance the specificity of
      detecting HSIL+ (CIN2-3+) lesions.

PMID- 29578258
TI  - Inheritance of von Willebrand disease Vicenza in a Japanese family.

PMID- 29578259
TI  - Photoregulating Antifouling and Bioadhesion Functional Coating Surface Based on
      Spiropyran.
AB  - Dynamic regulation of the interactions between specific molecules on functional
      surfaces and biomolecules, for example, proteins or cells, is critical for
      biosensor and biomedical devices. Herein, we present a spiropyran (SP)-based
      light-responsive surface coating, hPG (hyperbranched polyglycerol)-SP, to control
      the adsorption of proteins and adhesion of cells. In the normal state, the SP
      groups on the coating surface were in hydrophobic ring-closed form, which
      promotes the nonspecific protein adsorption and cell adhesion. Under UV
      irradiation, the grafted SP groups were dynamically isomerized into
      hydrophilic/zwitterionic merocyanine. Both hydrophilicity and zwitterions support
      the formation of a hydrated layer and hence the resulting hPG-MC coatings highly
      resist protein adsorption and cell adhesion. Moreover, the presented hPG also
      provided a robust bioinert background to suppress the nonspecific protein
      adsorption and cells adhesion. Therefore, this functionalized coating exhibited a
      good photoregulated antifouling behavior. Moreover, the detachment of adsorbed
      proteins and adhered cells from the coating surface was also realized.

PMID- 29578260
TI  - Dynamic multivoxel-localized 31 P MRS during plantar flexion exercise with
      variable knee angle.
AB  - Exercise studies investigating the metabolic response of calf muscles using 31 P
      MRS are usually performed with a single knee angle. However, during natural
      movement, the distribution of workload between the main contributors to force,
      gastrocnemius and soleus is influenced by the knee angle. Hence, it is of
      interest to measure the respective metabolic response of these muscles to
      exercise as a function of knee angle using localized spectroscopy. Time-resolved
      multivoxel 31 P MRS at 7 T was performed simultaneously in gastrocnemius medialis
      and soleus during rest, plantar flexion exercise and recovery in 12 healthy
      volunteers. This experiment was conducted with four different knee angles. PCr
      depletions correlated negatively with knee angle in gastrocnemius medialis,
      decreasing from 79+/-14 % (extended leg) to 35+/-23 %(~40 degrees ), and
      positively in soleus, increasing from 20+/-21 % to 36+/-25 %; differences were
      significant. Linear correlations were found between knee angle and end-exercise
      PCr depletions in gastrocnemius medialis (R2 =0.8) and soleus (R2 =0.53). PCr
      recovery times and end-exercise pH changes that correlated with PCr depletion
      were consistent with the literature in gastrocnemius medialis and differences
      between knee angles were significant. These effects were less pronounced in
      soleus and not significant for comparable PCr depletions. Maximum oxidative
      capacity calculated for all knee angles was in excellent agreement with the
      literature and showed no significant changes between different knee angles. In
      conclusion, these findings confirm that plantar flexion exercise with a straight
      leg is a suitable paradigm, when data are acquired from gastrocnemius only (using
      either localized MRS or small surface coils), and that activation of soleus
      requires the knee to be flexed. The present study comprises a systematic
      investigation of the effects of the knee angle on metabolic parameters, measured
      with dynamic multivoxel 31 P MRS during muscle exercise and recovery, and the
      findings should be used in future study design.

PMID- 29578261
TI  - Disparities exist between the dietary intake of Indigenous Australian women
      during pregnancy and the Australian dietary guidelines: the Gomeroi gaaynggal
      study.
AB  - BACKGROUND: Little is known about the adequacy of nutrient intakes and the
      overall diet quality of Indigenous Australian pregnant women. The aim of this
      cross-sectional study was to assess nutrient sufficiency and diet quality, as
      measured using the Australian Recommended Food Score (ARFS), in pregnant women
      from the Gomeroi gaaynggal cohort (n = 58). METHODS: Maternal dietary intake
      during pregnancy was assessed using the Australian Eating Survey Food Frequency
      Questionnaire, which was self-administered in the third trimester. Diet quality
      was determined using the ARFS. Food group servings and nutrient intakes were
      compared to the Australian Guide to Health Eating (AGHE) and Australian Nutrient
      Reference Values (NRVs). The current analysis examined the adequacy of usual
      intakes from food sources only, excluding supplements. RESULTS: None of the women
      met all AGHE daily food group serving recommendations. The highest alignment
      rates were for dairy (33%), meat/alternatives (31%) and vegetables (29.3%).
      Almost 93% of participants exceeded the recommended intake of energy-dense,
      nutrient-poor foods and percentage energy from saturated fat was high (15%). Of
      the five key nutrients for optimal reproductive health (folate, iron, calcium,
      zinc and fibre), the nutrients with the highest percentage of pregnant women
      achieving the NRVs were zinc (77.6%) and folate (68.9%), whereas iron was the
      lowest. Only one person achieved all NRVs (folate, iron, calcium, zinc and fibre)
      important in pregnancy. The median ARFS was 28 points (maximum of 73).
      CONCLUSIONS: Although the small cohort limits the generalisability of the
      findings of the present study, the data obtained indicate that the diets of these
      Indigenous pregnant women are inadequate. Therefore, strategies aiming to
      optimise nutrient intakes of Indigenous pregnant women are needed urgently.

PMID- 29578262
TI  - MicroRNA-guided gene expression in prostate cancer: Literature and database
      overview.
AB  - Insight into the aberrant expression of microRNAs (miRNAs) and the genes that
      they regulate during the progression of cancer in general and prostate cancer
      (PCa) in particular is one of the most important issues in current molecular
      biomedicine and allows for the discovery of therapeutic or diagnostic miRNA
      targets. The present study aimed to analyze the available data regarding the
      direct or indirect effects of miRNAs on the expression of the mRNAs involved in
      carcinogenesis and to enable updating and optimizing the selection of the
      corresponding targets. The present review focuses on the data related to the
      genes with miRNA-dependent expression during the development of PCa. The data
      used in this review have been extracted from research papers and the databases
      STRING, PANTHER and TargetScan, with a special focus on the genes directly
      associated with cell transformation and the maintenance of the transformed
      genotype, as well as tumor invasion and spread. The search for miRNA markers of
      PCa and therapeutically active molecules should rely on bioinformatics resources,
      such as data from recent experimental studies, as well as meta-analysis and cross
      analysis of the data on the state of the tumor, patient status,
      histological/immunohistological data and data on mRNA-miRNA coexpression.

PMID- 29578263
TI  - Telomere length determined by the fluorescence in situ hybridisation
      distinguishes malignant and benign cells in cytological specimens.
AB  - BACKGROUND: Telomeres are tandem repeats of TTAGGG at the end of eukaryotic
      chromosomes that play a key role in preventing chromosomal instability. The aim
      of the present study is to determine telomere length using fluorescence in situ
      hybridisation (FISH) on cytological specimens. METHODS: Aspiration samples (n =
      41) were smeared on glass slides and used for FISH. RESULTS: Telomere signal
      intensity was significantly lower in positive cases (cases with malignancy, n =
      25) as compared to negative cases (cases without malignancy, n = 16), and the
      same was observed for centromere intensity. The difference in DAPI intensity was
      not statistically significant. The ratio of telomere to centromere intensity did
      not show a significant difference between positive and negative cases. There was
      no statistical difference in the signal intensities of aspiration samples from
      ascites or pleural effusion (n = 23) and endoscopic ultrasound-guided FNA samples
      from the pancreas (n = 18). CONCLUSIONS: The present study revealed that telomere
      length can be used as an indicator to distinguish malignant and benign cells in
      cytological specimens. This novel approach may help improve diagnosis for cancer
      patients.

PMID- 29578264
TI  - Influence of Different Implant Geometry in Clinical Longevity and Maintenance of
      Marginal Bone: A Systematic Review.
AB  - PURPOSE: To assess, through a systematic review, the influence of different
      implant geometries on clinical longevity and maintenance of marginal bone tissue.
      METHODS: An electronic search was conducted in MEDLINE, Scopus, and Web of
      Science databases, limited to studies written in English from 1996 to 2017 using
      specific search strategies. Only randomized controlled trials (RCTs) that
      compared dental implants and their geometries were included. Two reviewers
      independently selected studies, extracted data, and assessed the risk of bias of
      included studies. RESULTS: From the 4006 references identified by the search, 24
      were considered eligible for full-text analysis, after which 10 studies were
      included in this review. A similar behavior of marginal bone loss between tapered
      and cylindrical geometries was observed; however, implants that had micro-threads
      in the neck presented a slight decrease of marginal bone loss compared to
      implants with straight or smooth neck. Success and survival rates were high, with
      cylindrical implants presenting higher success and survival rates than tapered
      ones. CONCLUSIONS: Implant geometry seems to have little influence on marginal
      bone loss (MBL) and survival and success rates after 1 year of implant placement;
      however, the evidence in this systematic review was classified as very low due to
      limitations such as study design, sample size, and publication bias. Thus, more
      well-designed RCTs should be conducted to provide evidence regarding the
      influence of implant geometry on MBL and survival and success rates after 1 year
      of implant placement.

PMID- 29578265
TI  - Core-Shell Double Gyroid Structure Formed by Linear ABC Terpolymer Thin Films.
AB  - The synthesis and self-assembly in thin-film configuration of linear ABC triblock
      terpolymer chains consisting of polystyrene (PS), poly(2-vinylpyridine) (P2VP),
      and polyisoprene (PI) are described. For that purpose, a hydroxyl-terminated PS-b
      P2VP (45 kg mol-1 ) building block and a carboxyl-terminated PI (9 kg mol-1 ) are
      first separately prepared by anionic polymerization, and then are coupled via a
      Steglich esterification reaction. This quantitative and metal-free catalyst
      synthesis route reveals to be very interesting since functionalization and
      purification steps are straightforward, and well-defined terpolymers are
      produced. A solvent vapor annealing (SVA) process is used to promote the self
      assembly of frustrated PS-b-P2VP-b-PI chains into a thin-film core-shell double
      gyroid (Q230 , space group: Ia3-d) structure. As terraces are formed within PS-b
      P2VP-b-PI thin films during the SVA process under a CHCl3 vapor, different plane
      orientations of the Q230 structure ((211), (110), (111), and (100)) are observed
      at the polymer-air interface depending on the film thickness.

PMID- 29578266
TI  - Diagnostic performance of cone beam computed tomography in assessing peri-implant
      bone loss: A systematic review.
AB  - OBJECTIVES: To evaluate the diagnostic performance of cone beam computed
      tomography (CBCT) in the assessment of peri-implant bone loss and analyze its
      influencing factors. MATERIALS AND METHODS: Clinical and preclinical studies
      reporting diagnostic outcomes of CBCT imaging of peri-implant bone loss compared
      to direct reference measurements were sought by searching five electronic
      databases, PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL Plus, and
      OpenGrey. QUADAS-2 criteria were adapted for quality analysis of the included
      studies. A qualitative synthesis was performed. Two meta-analysis models (random
      effects and mixed-effects) summarized the area under receiver operating
      characteristic (AUC) curve observations reported in the selected studies. The
      mixed-effects meta-analysis model evaluated three possible influencing factors,
      "defect type," "defect size," and "study effect." RESULTS: The initial search
      yielded 3,716 titles, from which 18 studies (13 in vitro and 5 animal) were
      included. Diagnostic accuracy of CBCT was fair to excellent in detecting in vitro
      circumferential-intrabony and fenestration defects, but moderate to low for peri
      implant dehiscences, and tended to be higher for larger defect sizes. Both, over-
      and underestimation of linear measurements were reported for the animal models.
      The meta-analyses included 37 AUC observations from eight studies. The random
      effects model showed significant heterogeneity. The mixed-effects model exhibited
      also significant but lower heterogeneity, and "defect type" and "study effect"
      significantly influenced the variability of AUC observations. CONCLUSION: In
      vitro, CBCT performs well in detecting peri-implant circumferential-intrabony or
      fenestration defects but less in depicting dehiscences. Influencing factors due
      to other site-related and technical parameters on the diagnostic outcome need to
      be addressed further in the future studies.

PMID- 29578267
TI  - A Review on Recent Developments and Prospects for the Oxygen Reduction Reaction
      on Hollow Pt-alloy Nanoparticles.
AB  - Due to their interesting electrocatalytic properties for the oxygen reduction
      reaction (ORR), hollow Pt-alloy nanoparticles (NPs) supported on high-surface
      area carbon attract growing interest. However, the suitable synthesis methods and
      associated mechanisms of formation, the reasons for their enhanced specific
      activity for the ORR, and the nature of adequate alloying elements and carbon
      supports for this type of nanocatalysts remain open questions. This Review aims
      at shedding light on these topics with a special emphasis on hollow PtNi NPs
      supported onto Vulcan C (PtNi/C). We first show how hollow Pt-alloy/C NPs can be
      synthesized by a mechanism involving galvanic replacement and the nanoscale
      Kirkendall effect. Nickel, cobalt, copper, zinc, and iron (Ni, Co, Cu, Zn, and
      Fe, respectively) were tested for the formation of Pt-alloy/C hollow
      nanostructures. Our results indicate that metals with standard potential 
      0.4<E<0.4 V (vs. the normal hydrogen electrode) and propensity to spontaneously
      form metal borides in the presence of sodium borohydride are adequate sacrificial
      templates. As they lead to smaller hollow Pt-alloy/C NPs, mesoporous carbon
      supports are also best suited for this type of synthesis. A comparison of the
      electrocatalytic activity towards the ORR or the electrooxidation of a COads
      monolayer, methanol or ethanol of hollow and solid Pt-alloy/C NPs underlines the
      pivotal role of the structural disorder of the metal lattice, and is supported by
      ab initio calculations. As evidenced by accelerated stress tests simulating
      proton-exchange membrane fuel cell cathode operating conditions, the beneficial
      effect of structural disorder is maintained on the long term, thereby bringing
      promises for the synthesis of highly active and robust ORR electrocatalysts.

PMID- 29578269
TI  - Successful treatment of acquired von Willebrand disease with lenalidomide leading
      to dramatic resolution of intractable gastrointestinal bleeding: A case report.

PMID- 29578268
TI  - Chemical-to-Electricity Carbon: Water Device.
AB  - The ability to release, as electrical energy, potential energy stored at the
      water:carbon interface is attractive, since water is abundant and available.
      However, many previous reports of such energy converters rely on either flowing
      water or specially designed ionic aqueous solutions. These requirements restrict
      practical application, particularly in environments with quiescent water. Here, a
      carbon-based chemical-to-electricity device that transfers the chemical energy to
      electrical form when coming into contact with quiescent deionized water is
      reported. The device is built using carbon nanotube yarns, oxygen content of
      which is modulated using oxygen plasma-treatment. When immersed in water, the
      device discharges electricity with a power density that exceeds 700 mW m-2 , one
      order of magnitude higher than the best previously published result. X-ray
      absorption and density functional theory studies support a mechanism of operation
      that relies on the polarization of sp2 hybridized carbon atoms. The devices are
      incorporated into a flexible fabric for powering personal electronic devices.

PMID- 29578270
TI  - Singlet Oxygen and the Origin of Oxygen Functionalities on the Surface of Carbon
      Electrodes.
AB  - The generation of oxygen-containing functionalities on pristine carbon surfaces
      is investigated and shown to be light sensitive, specifically to infra-red
      radiation. A mechanistic route involving singlet oxygen, 1 O2 , is proposed and
      evidenced.

PMID- 29578272
TI  - Pleased to edit you: discovering the world of science as a journal editor.

PMID- 29578271
TI  - Psychoeducation for psychiatric inpatients following remission of a manic episode
      in bipolar I disorder: A randomized controlled trial.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effectiveness of
      psychoeducation for bipolar I inpatients following remission of a manic episode
      in a Chinese population. METHOD: The study recruited currently medicated bipolar
      I patients, aged 18-60 years, who were in remission from a manic episode, as
      determined using the Diagnostic and Statistical Manual of Mental Disorders Fifth
      Edition (DSM-5). Patients were randomized (1:1) to either eight sessions of group
      based psychoeducation (active treatment group) or regular free discussions
      (control group). The primary outcomes were the rates of any type of recurrence
      and rehospitalization following treatment. The secondary outcomes were changes in
      mood symptoms, medication adherence, global functioning, as well as treatment
      response (as measured using the Clinical Global Impression scale). Subjects were
      assessed at baseline and then at 2 weeks, and 1, 2, 3, 5, 7, 9, and 12 months
      following treatment. RESULTS: At 1 year, patients receiving the psychoeducation
      treatment demonstrated significantly less recurrence. Those in the treatment
      group also showed a significant reduction in mania recurrence but not depressive
      recurrence, and psychoeducation increased time to remission. Notably, lower rates
      of rehospitalization were found in the active treatment group. Those receiving
      the psychoeducation treatment also revealed higher change from baseline on
      measures of depression (17-item Hamilton Rating Scale for Depression), mania
      (Young Mania Rating Scale), global functioning (Clinical Global Impression
      severity scale and World Health Organization Disability Assessment Schedule)
      (P<.05). However, there were no significant group differences for the medication
      adherence scores. CONCLUSION: This preliminary evidence suggests that short,
      group-based psychoeducation benefits currently medicated inpatients following the
      remission of mania in bipolar I disorder. This intervention warrants further
      investigation, especially in other Chinese populations. If future studies confirm
      its benefits, group-based psychoeducation could be incorporated into routine
      psychiatric inpatient care for bipolar patients in China.

PMID- 29578273
TI  - Another Unprecedented Wieland Mechanism Confirmed: Hydrogen Formation from
      Hydrogen Peroxide, Formaldehyde, and Sodium Hydroxide.
AB  - In 1923, Wieland and Wingler reported that in the molecular hydrogen producing
      reaction of hydrogen peroxide with formaldehyde in basic solution, free hydrogen
      atoms (H. ) are not involved. They postulated that bis(hydroxymethyl)peroxide,
      HOCH2 OOCH2 OH, is the intermediate, which decomposes to yield H2 and formate,
      proposing a mechanism that would nowadays be considered as a "concerted process".
      Since then, several other (conflicting) "mechanisms" have been suggested. Our NMR
      and Raman spectroscopic and kinetic studies, particularly the determination of
      the deuterium kinetic isotope effect (DKIE), now confirm that in this base
      dependent reaction, both H atoms of H2 derive from the CH2 hydrogen atoms of
      formaldehyde, and not from the OH groups of HOCH2 OOCH2 OH or from water. Quantum
      chemical CBS-QB3 and W1BD computations show that H2 release proceeds through a
      concerted process, which is strongly accelerated by double deprotonation of HOCH2
      OOCH2 OH, thereby ruling out a free radical pathway.

PMID- 29578274
TI  - Desmopressin stimulation testing: Response to intravenous and intranasal forms.
AB  - INTRODUCTION: Desmopressin is commonly used to reduce bleeding in patients with
      mucocutaneous bleeding disorders and is available in both intravenous and
      intranasal forms. Given the variability in response to desmopressin at an
      individual level, its effectiveness should be assessed with a test dose prior to
      being advised for use. At this time, no trial has extensively compared the use of
      intranasal desmopressin to intravenous desmopressin. AIMS: To determine whether
      both forms of desmopressin are equally effective in yielding a positive response
      in laboratory assays in paediatric patients with von Willebrand disease or
      probable von Willebrand disease. METHODS: We evaluated medical record data for 58
      patients who underwent desmopressin stimulation testing in our haematology clinic
      during a 1-year period. Data were collected on demographic information and
      haematologic laboratory assays prior to desmopressin administration and one hour
      following desmopressin. RESULTS: There was an absolute increase in von Willebrand
      antigen to levels appropriate for haemostasis following both forms of
      desmopressin, although this increase was significantly greater in the intravenous
      group compared to the intranasal group. There was also a significant absolute
      increase in Ristocetin Cofactor and Factor VIII levels following desmopressin in
      both groups. CONCLUSION: Both intravenous and intranasal forms of desmopressin
      produce a positive response during desmopressin stimulation testing and can be
      used to identify patients for whom this medication would be effective.

PMID- 29578275
TI  - Experimental Identification of Ultrafast Reverse Hole Transfer at the Interface
      of the Photoexcited Methanol/Graphitic Carbon Nitride System.
AB  - An experimental scrutiny of the photoexcited hole dynamics in a prototypical
      system is presented in which hole-scavenging methanol molecules are chemisorbed
      on a graphitic carbon nitride (g-C3 N4 ) substrate. A set of comparison and
      control experiments by means of femtosecond time-resolved transient absorption
      (fs-TA) spectroscopy were conducted. The elusive reverse hole transfer (RHT)
      process was identified, which occurs on a timescale of a few hundred picoseconds.
      The critical role of interfacially chemisorbed methoxy (instead of methanol) as
      the dominant species responsible for hole scavenging was confirmed by a control
      experiment using protonated g-C3 N4 as the substrate. A hot-hole transfer effect
      was revealed by implementing different interband photoexcitation scenarios. The
      RHT rate is the key factor governing the hole-scavenging ability of different
      hole scavengers.

PMID- 29578276
TI  - Thermo-Driven Controllable Emulsion Separation by a Polymer-Decorated Membrane
      with Switchable Wettability.
AB  - A thermoresponsive Poly(N-isopropylacrylamide) (PNIPAAm)-modified nylon membrane
      was fabricated via hydrothermal route. Combining rough structure, proper pore
      size, and thermoresponsive wettability, the membrane can separate at least 16
      types of stabilized oil-in-water and water-in-oil emulsions at different
      temperatures. Below the LCST (ca. 25  degrees C), the material exhibits
      hydrophilicity and underwater superoleophobicity, which can be used for the
      separation of various kinds of oil-in-water emulsions. Above the LCST (ca. 45 
      degrees C), the membrane shows the opposite property with high hydrophobicity and
      superoleophilicity, and it can then separate stabilized water-in-oil emulsions.
      The material exhibits excellent recyclability and high separation efficiency for
      various kinds of emulsions and the hydrothermal method is facile and low-cost.
      The membrane shows good potential in real situations such as on-demand oil-spill
      cleanup, industrial wastewater treatment, remote operation of oil/water emulsion
      separation units, and fuel purification.

PMID- 29578277
TI  - Understanding the Pathways from Depression to Suicidal Risk from the Perspective
      of the Interpersonal-Psychological Theory of Suicide.
AB  - Suicide is a major public health concern, especially in adolescence. Identifying
      risk factors for suicide is important to effectively prevent such behavior.
      Depression is one of the most widely examined risk factors for suicidal risk. How
      depression and suicidal risk are related, however, is still not clear. This study
      tested a model with three key constructs of the interpersonal-psychological
      theory of suicidal behavior (IPTS)-perceived burdensomeness, thwarted
      belongingness, and nonsuicidal self-injury (NSSI)-as mediators in the
      relationship between depression and suicidal risk among Chinese adolescents.
      Chinese high school students (N = 1,074; 54.2% male; Mage  = 13.87 years, SD =
      1.48) completed questionnaires assessing all study variables. Results suggested
      that perceived burdensomeness and NSSI partially mediated the relationship
      between depression and suicidal risk. Findings of this study emphasize the
      importance of the IPTS framework in understanding the possible mechanisms
      underlying the relationship between depression and suicidal risk, and suggest a
      possible avenue for suicide interventions.

PMID- 29578278
TI  - Sudden swelling of face and neck following colonoscopy.

PMID- 29578279
TI  - Commentary on "Psychosis in bipolar disorder: Does it represent a more 'severe'
      illness?"

PMID- 29578280
TI  - Factors associated with underuse of mineralocorticoid receptor antagonists in
      heart failure with reduced ejection fraction: an analysis of 11 215 patients from
      the Swedish Heart Failure Registry.
AB  - AIM: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart
      failure with reduced ejection fraction (HFrEF), but are underutilized.
      Hyperkalaemia may be one reason, but the underlying reasons for underuse are
      unknown. The aim of this study was to investigate the independent predictors of
      MRA underuse in a large and unselected HFrEF cohort. METHODS AND RESULTS: We
      included patients with HFrEF (ejection fraction <40%), New York Heart Association
      (NYHA) class II-IV and heart failure (HF) duration >=6 months from the Swedish HF
      Registry. Logistic regression analysis identified independent associations
      between 39 demographic, clinical, co-treatment, and socioeconomic predictors and
      MRA non-use. Of 11 215 patients, 27% were women; mean age was 75 +/- 11 years;
      only 4443 (40%) patients received MRA. Selected characteristics independently
      associated with MRA non-use were in descending order of magnitude: lower
      creatinine clearance (<60 mL/min), no need for diuretics, no cardiac
      resynchronization therapy/implantable cardioverter-defibrillator, higher blood
      pressure, no digoxin use, higher ejection fraction, outpatient setting, older
      age, lower income, ischaemic heart disease, male sex, follow-up in primary vs.
      specialty care, lower NYHA class, and absence of hypertension diagnosis. Plasma
      potassium and N-terminal pro B-type natriuretic peptide levels were not
      associated with MRA non-use. CONCLUSION: Mineralocorticoid receptor antagonists
      remain underused in HFrEF. Their use does not decrease with elevated potassium
      but does with impaired renal function, even in the creatinine clearance 30-59.9
      mL/min range where MRAs are not contraindicated. MRA underuse may be further
      related to non-specialist care, milder HF and no use of other HF therapy.

PMID- 29578281
TI  - Benefit of mepolizumab treatment in a patient with chronic spontaneous urticaria.

PMID- 29578282
TI  - Rash, fever and arthralgia in a 19-year-old woman.

PMID- 29578283
TI  - Non-IgE-dependent hypersensitivity to macrogol 6000.

PMID- 29578284
TI  - Long-term prognosis, subsequent pregnancy, contraception and overall management
      of peripartum cardiomyopathy: practical guidance paper from the Heart Failure
      Association of the European Society of Cardiology Study Group on Peripartum
      Cardiomyopathy.
AB  - Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart
      failure secondary to left ventricular systolic dysfunction towards the end of
      pregnancy or in the months following delivery, where no other cause for heart
      failure is identified. Outcome varies from full recovery to residual left
      ventricular systolic dysfunction and even death. Many women return to their
      physician to acquire information on their long-term prognosis, to seek medical
      advice regarding contraception, or when planning a subsequent pregnancy. This
      position paper summarizes current evidence for long-term outcome, risk
      stratification of further pregnancies and overall management. Based on the best
      available evidence, as well as the clinical experience of the European Society of
      Cardiology Study Group on Peripartum Cardiomyopathy members, a consensus on pre-
      and postpartum management algorithms for women undergoing a subsequent pregnancy
      is presented.

PMID- 29578285
TI  - Comparative Proteomics Analysis Reveals Trans Fatty Acid Isomers Activates
      Different Pathways in Human Umbilical Vein Endothelial Cell.
AB  - Trans fatty acid (TFA), a group of unsaturated fats with at least one double bond
      in the trans configuration, plays a role in lipid metabolism, the structure of
      the cell membrane phospholipids, and apoptosis. Previous studies demonstrated
      that TFA was associated with coronary heart disease, obesity, and insulin
      resistance. Herein, a quantitative proteomics approach estimated the relative
      abundance of proteins in human umbilical vein endothelial cells treated with TFA
      (two different TFA structural isomers: 9t-18:1 and 9t,12t-18:2). The results
      revealed that 174 identified proteins were significantly altered with respect to
      expression. Furthermore, based on the cutoff values, 35 proteins were
      differentially expressed in the 9t-18:1 group as compared to the control group,
      69 proteins were differentially expressed in 9t,12t-18:2 group as compared to the
      control group, and 120 proteins were differentially expressed in the 9t,12t-18:2
      group as compared to the 9t-18:1 group. Based on the bioinformatics analysis, we
      found that TFA could alter the structural constitution of the cytoskeleton
      through protein interactions, localization into the cell membrane, and
      incorporation into the phospholipid of the cell. In addition, 17 differential
      apoptosis-related proteins, including cell division cycle 42, superoxide
      dismutase 1, glyoxalase I, and macrophage migration inhibitory factor were also
      identified. Together, these results might emphasize the need for studying TFA
      induced biological processes.

PMID- 29578286
TI  - PIK3CA-related overgrowth spectrum: concurrence of multiple anomalies in one
      patient.

PMID- 29578287
TI  - Enhanced spectrofluorimetric determination of two novel combination therapies for
      the treatment of benign prostatic hyperplasia containing tamsulosin
      hydrochloride.
AB  - Two novel combination therapies for the treatment of benign prostatic hyperplasia
      were analyzed using simple and enhanced spectrofluorimetric methods based on
      derivative and derivative ratio techniques. The two combinations contained
      tamsulosin hydrochloride (TAM) as a minor component with tolterodine tartrate
      (TOL) or solifenacin succinate (SOL). The fluorescence of the three drugs under
      study was measured in methanolic water solution. For the TAM and SOL mixture,
      successful resolution between both drugs was achieved by derivative manipulation
      of both ratio and zero-order emission spectra with good linearity in the ranges
      of 0.75-3.50 and 2.5-15.0 MUg ml-1 for TAM and SOL, respectively. Extensive
      emission spectral overlap was observed for the TAM and TOL mixture. Therefore,
      only derivative application of the ratio emission spectra resolved such overlap
      and quantitated TAM and TOL simultaneously in the ranges 0.75-3.50 and 2.5-20.0
      MUg ml-1 for TAM and TOL, respectively. Optimization of various experimental
      parameters that affected the fluorescence intensity of the three drugs was
      performed. Successful application of all proposed methods was achieved for
      analysis of the two drugs in each combination therapy in their laboratory
      prepared mixtures and dosage forms with good accuracy and precision.

PMID- 29578288
TI  - Differential growth of pavement cells of Arabidopsis thaliana leaf epidermis as
      revealed by microbead labeling.
AB  - PREMISE OF THE STUDY: In numerous vascular plants, pavement cells of the leaf
      epidermis are shaped like a jigsaw-puzzle piece. Knowledge about the subcellular
      pattern of growth that accompanies morphogenesis of such a complex shape is
      crucial for studies of the role of the cytoskeleton, cell wall and phytohormones
      in plant cell development. Because the detailed growth pattern of the anticlinal
      and periclinal cell walls remains unknown, our aim was to measure pavement cell
      growth at a subcellular resolution. METHODS: Using fluorescent microbeads applied
      to the surface of the adaxial leaf epidermis of Arabidopsis thaliana as landmarks
      for growth computation, we directly assessed the growth rates for the outer
      periclinal and anticlinal cell walls at a subcellular scale. KEY RESULTS: We
      observed complementary tendencies in the growth pattern of the outer periclinal
      and anticlinal cell walls. Central portions of periclinal walls were
      characterized by relatively slow growth, while growth of the other wall portions
      was heterogeneous. Local growth of the periclinal walls accompanying lobe
      development after initiation was relatively fast and anisotropic, with maximal
      extension usually in the direction along the lobe axis. This growth pattern of
      the periclinal walls was complemented by the extension of the anticlinal walls,
      which was faster on the lobe sides than at the tips. CONCLUSIONS: Growth of the
      anticlinal and outer periclinal walls of leaf pavement cells is heterogeneous.
      The growth of the lobes resembles cell elongation via diffuse growth rather than
      tip growth.

PMID- 29578289
TI  - Timing is everything: Dichogamy and pollen germinability underlie variation in
      autonomous selfing among populations.
AB  - PREMISE OF THE STUDY: The evolution of multiple floral traits often underlies the
      transition from outcrossing to selfing. Such traits can influence the ability to
      self, and the timing at which selfing occurs, which in turn affects the costs of
      selfing. Species that display variation in autonomous selfing provide an
      opportunity to dissect the phenotypic changes that contribute to variability in
      the mating system. METHODS: In a common garden, we measured dichogamy and
      herkogamy in 24 populations of the protandrous mixed-mating herb Campanula
      americana, and related these to autonomous fruit set (autonomy). We then measured
      the timing of self-pollen deposition and fruit production in populations with
      high and low autonomy, and determined whether pollen germinability across floral
      development contributes to variation in autonomy. KEY RESULTS: Populations that
      transitioned more rapidly to female phase displayed elevated autonomous selfing,
      but herkogamy was unassociated with autonomous selfing. Selfing occurred more
      rapidly in highly autonomous populations because of greater self-pollen
      deposition early in female phase. Pollen germinability in low-autonomy
      populations remained constant across floral development, but in high-autonomy
      populations it increased after floral anthesis and was highest near the onset of
      female phase. CONCLUSIONS: Reduced dichogamy, elevated self-pollen deposition,
      and higher pollen germination late in male phase contribute to both earlier
      selfing and greater selfing. These traits vary among populations, likely
      reflecting past selection on the mating system. While delayed selfing bears fewer
      fitness costs, the evolution of earlier selfing may be favored if self-pollen
      availability decreases over floral development.

PMID- 29578290
TI  - Limited pollen dispersal, small genetic neighborhoods, and biparental inbreeding
      in Vallisneria americana.
AB  - PREMISE OF THE STUDY: Pollen dispersal is a key process that influences
      ecological and evolutionary dynamics of plant populations by facilitating sexual
      reproduction and gene flow. Habitat loss and fragmentation have the potential to
      reduce pollen dispersal within and among habitat patches. We assessed aquatic
      pollen dispersal and mating system characteristics in Vallisneria americana-a
      water-pollinated plant with a distribution that has been reduced from historic
      levels. METHODS: We examined pollen neighborhood size, biparental inbreeding, and
      pollen dispersal, based on seed paternity using the indirect paternity method
      KinDist, from samples of 18-39 mothers and 14-20 progeny per mother from three
      sites across 2 years. KEY RESULTS: On average, fruits contained seeds sired by
      seven fathers. We found significant biparental inbreeding and limited pollen
      dispersal distances (0.8-4.34 m). However, in a number of cases, correlated
      paternity did not decline with distance, and dispersal could not be reliably
      estimated. CONCLUSIONS: Frequent pollen dispersal is not expected among patches,
      and even within patches, gene flow via pollen will be limited. Limited pollen
      dispersal establishes genetic neighborhoods, which, unless overcome by seed and
      propagule dispersal, will lead to genetic differentiation even in a continuous
      population. Unless loss and fragmentation drive populations to extreme sex bias,
      local pollen dispersal is likely to be unaffected by habitat loss and
      fragmentation per se because the spatial scale of patch isolation already exceeds
      pollen dispersal distances. Therefore, managing specifically for pollen
      connectivity is only relevant over very short distances.

PMID- 29578291
TI  - Polar auxin transport is implicated in vessel differentiation and spatial
      patterning during secondary growth in Populus.
AB  - PREMISE OF THE STUDY: Dimensions and spatial distribution of vessels are
      critically important features of woody stems, allowing for adaptation to
      different environments through their effects on hydraulic efficiency and
      vulnerability to embolism. Although our understanding of vessel development is
      poor, basipetal transport of auxin through the cambial zone may play an important
      role. METHODS: Stems of Populus tremula *alba were treated with the auxin
      transport inhibitor N-1-naphthylphthalamic acid (NPA) in a longitudinal strip
      along the length of the lower stem. Vessel lumen diameter, circularity, and
      length; xylem growth; tension wood area; and hydraulic conductivity before and
      after a high pressure flush were determined on both NPA-treated and control
      plants. KEY RESULTS: NPA-treated stems formed aberrant vessels that were short,
      small in diameter, highly clustered, and angular in cross section, whereas xylem
      formed on the untreated side of the stem contained typical vessels that were
      similar to those of controls. NPA-treated stems had reduced specific conductivity
      relative to controls, but this difference was eliminated by the high-pressure
      flush. The control treatment (lanolin + dimethyl sulfoxide) reduced xylem growth
      and increased tension wood formation, but never produced the aberrant vessel
      patterning seen in NPA-treated stems. CONCLUSIONS: These results are consistent
      with a model of vessel development in which basipetal polar auxin transport
      through the xylem-side cambial derivatives is required for proper expansion and
      patterning of vessels and demonstrate that reduced auxin transport can produce
      stems with altered stem hydraulic properties.

PMID- 29578292
TI  - Vessel-associated cells in angiosperm xylem: Highly specialized living cells at
      the symplast-apoplast boundary.
AB  - BACKGROUND: Vessel-associated cells (VACs) are highly specialized, living
      parenchyma cells that are in direct contact with water-conducting, dead vessels.
      The contact may be sparse or in large tight groups of parenchyma that completely
      surrounds vessels. VACs differ from vessel distant parenchyma in physiology,
      anatomy, and function and have half-bordered pits at the vessel-parenchyma
      juncture. The distinct anatomy of VACs is related to the exchange of substances
      to and from the water-transport system, with the cells long thought to be
      involved in water transport in woody angiosperms, but where direct experimental
      evidence is lacking. SCOPE: This review focuses on our current knowledge of VACs
      regarding anatomy and function, including hydraulic capacitance, storage of
      nonstructural carbohydrates, symplastic and apoplastic interactions, defense
      against pathogens and frost, osmoregulation, and the novel hypothesis of
      surfactant production. Based on microscopy, we visually represent how VACs vary
      in dimensions and general appearance between species, with special attention to
      the protoplast, amorphous layer, and the vessel-parenchyma pit membrane.
      CONCLUSIONS: An understanding of the relationship between VACs and vessels is
      crucial to tackling questions related to how water is transported over long
      distances in xylem, as well as defense against pathogens. New avenues of research
      show how parenchyma-vessel contact is related to vessel diameter and a new
      hypothesis may explain how surfactants arising from VAC can allow water to travel
      under negative pressure. We also reinforce the message of connectivity between
      VAC and other cells between xylem and phloem.

PMID- 29578293
TI  - Challenges and questions in reconstructing the ancestral flower of angiosperms: A
      reply to Sokoloff et al.

PMID- 29578294
TI  - From the sap's perspective: The nature of vessel surfaces in angiosperm xylem.
AB  - PREMISE OF THE STUDY: Xylem sap in angiosperms moves under negative pressure in
      conduits and cell wall pores that are nanometers to micrometers in diameter, so
      sap is always very close to surfaces. Surfaces matter for water transport because
      hydrophobic ones favor nucleation of bubbles, and surface chemistry can have
      strong effects on flow. Vessel walls contain cellulose, hemicellulose, lignin,
      pectins, proteins, and possibly lipids, but what is the nature of the inner,
      lumen-facing surface that is in contact with sap? METHODS: Vessel lumen surfaces
      of five angiosperms from different lineages were examined via transmission
      electron microscopy and confocal and fluorescence microscopy, using fluorophores
      and autofluorescence to detect cell wall components. Elemental composition was
      studied by energy-dispersive X-ray spectroscopy, and treatments with
      phospholipase C (PLC) were used to test for phospholipids. KEY RESULTS: Vessel
      surfaces consisted mainly of lignin, with strong cellulose signals confined to
      pit membranes. Proteins were found mainly in inter-vessel pits and pectins only
      on outer rims of pit membranes and in vessel-parenchyma pits. Continuous layers
      of lipids were detected on most vessel surfaces and on most pit membranes and
      were shown by PLC treatment to consist at least partly of phospholipids.
      CONCLUSIONS: Vessel surfaces appear to be wettable because lignin is not strongly
      hydrophobic and a coating with amphiphilic lipids would render any surface
      hydrophilic. New questions arise about these lipids and their possible origins
      from living xylem cells, especially about their effects on surface tension,
      surface bubble nucleation, and pit membrane function.

PMID- 29578295
TI  - Intercontinental dispersal and whole-genome duplication contribute to loss of
      self-incompatibility in a polyploid complex.
AB  - PREMISE OF THE STUDY: Angiosperm species often shift from self-incompatibility to
      self-compatibility following population bottlenecks. Across the range of a
      species, population bottlenecks may result from multiple factors, each of which
      may affect the geographic distribution and magnitude of mating-system shifts. We
      describe how intercontinental dispersal and genome duplication facilitate loss of
      self-incompatibility. METHODS: Self and outcross pollinations were performed on
      plants from 24 populations of the Campanula rotundifolia polyploid complex.
      Populations spanned the geographic distribution and three dominant cytotypes of
      the species (diploid, tetraploid, hexaploid). KEY RESULTS: Loss of self
      incompatibility was associated with both intercontinental dispersal and genome
      duplication. European plants were largely self-incompatible, whereas North
      American plants were intermediately to fully self-compatible. Within both
      European and North American populations, loss of self-incompatibility increased
      as ploidy increased. Ploidy change and intercontinental dispersal both
      contributed to loss of self-incompatibility in North America, but range expansion
      did not affect self-incompatibility within Europe or North America. CONCLUSIONS:
      When species are subject to population bottlenecks arising through multiple
      factors, each factor can contribute to self-incompatibility loss. In a widespread
      polyploid complex, the loss of self-incompatibility can be predicted by the
      cumulative effects of whole-genome duplication and intercontinental dispersal.

PMID- 29578296
TI  - Novel climates reverse carbon uptake of atmospherically dependent epiphytes:
      Climatic constraints on the iconic boreal forest lichen Evernia mesomorpha.
AB  - PREMISE OF THE STUDY: Changing climates are expected to affect the abundance and
      distribution of global vegetation, especially plants and lichens with an
      epiphytic lifestyle and direct exposure to atmospheric variation. The study of
      epiphytes could improve understanding of biological responses to climatic
      changes, but only if the conditions that elicit physiological performance changes
      are clearly defined. METHODS: We evaluated individual growth performance of the
      epiphytic lichen Evernia mesomorpha, an iconic boreal forest indicator species,
      in the first year of a decade-long experiment featuring whole-ecosystem warming
      and drying. Field experimental enclosures were located near the southern edge of
      the species' range. KEY RESULTS: Mean annual biomass growth of Evernia
      significantly declined 6 percentage points for every +1 degrees C of experimental
      warming after accounting for interactions with atmospheric drying. Mean annual
      biomass growth was 14% in ambient treatments, 2% in unheated control treatments,
      and -9% to -19% (decreases) in energy-added treatments ranging from +2.25 to
      +9.00 degrees C above ambient temperatures. Warming-induced biomass losses among
      persistent individuals were suggestive evidence of an extinction debt that could
      precede further local mortality events. CONCLUSIONS: Changing patterns of warming
      and drying would decrease or reverse Evernia growth at its southern range
      margins, with potential consequences for the maintenance of local and regional
      populations. Negative carbon balances among persisting individuals could
      physiologically commit these epiphytes to local extinction. Our findings
      illuminate the processes underlying local extinctions of epiphytes and suggest
      broader consequences for range shrinkage if dispersal and recruitment rates
      cannot keep pace.

PMID- 29578297
TI  - High-throughput sequencing data clarify evolutionary relationships among North
      American Vitis species and improve identification in USDA Vitis germplasm
      collections.
AB  - PREMISE OF THE STUDY: Grapes are one of the most economically important berry
      crops worldwide, with the vast majority of production derived from the
      domesticated Eurasian species Vitis vinifera. Expansion of production into new
      areas, development of new cultivars, and concerns about adapting grapevines for
      changing climates necessitate the use of wild grapevine species in breeding
      programs. Diversity within Vitis has long been a topic of study; however,
      questions remain regarding relationships between species. Furthermore, the
      identity of some living accessions is unclear. METHODS: This study generated
      11,020 single nucleotide polymorphism (SNP) markers for more than 300 accessions
      in the USDA-ARS grape germplasm repository using genotyping-by-sequencing.
      Resulting data sets were used to reconstruct evolutionary relationships among
      several North American and Eurasian Vitis species, and to suggest taxonomic
      labels for previously unidentified and misidentified germplasm accessions based
      on genetic distance. KEY RESULTS: Maximum likelihood analyses of SNP data support
      the monophyly of Vitis, subg. Vitis, a Eurasian subg. Vitis clade, and a North
      American subg. Vitis clade. Data delineate species groups within North America.
      In addition, analysis of genetic distance suggested taxonomic identities for 20
      previously unidentified Vitis accessions and for 28 putatively misidentified
      accessions. CONCLUSIONS: This work advances understanding of Vitis evolutionary
      relationships and provides the foundation for ongoing germplasm enhancement. It
      supports conservation and breeding efforts by contributing to a growing genetic
      framework for identifying novel genetic variation and for incorporating new,
      unsampled populations into the germplasm repository system.

PMID- 29578298
TI  - Duration of propagule pressure affects non-native plant species abundances.
AB  - PREMISE OF THE STUDY: Invasions by non-native species are known to be related to
      present propagule pressure (e.g., the number of non-native seeds arriving in a
      site each year). However, previous studies have mostly ignored the potential
      effects of the length of time that a site has experienced propagule pressure.
      This study is novel in studying past as well as present propagule pressure and in
      demonstrating the importance of past propagule pressure. METHODS: We tested the
      importance of past and present propagule pressure in three plant communities in
      central Texas to quantify relationships between variables representing past and
      present propagule pressure, other environmental variables, and the abundance of
      non-native and native woody plant species. KEY RESULTS: Duration of propagule
      pressure predicted non-native species richness. Sites had greater non-native
      species richness if they were nearer to development (houses, roads) and if nearby
      development was older. While mesic woodlands had the most native species,
      streamside woodlands had the most non-native species. CONCLUSIONS: First, future
      studies of non-native invasions would benefit from including past as well as
      present propagule pressure. If past propagule pressure is not considered, its
      effects may be wrongly ascribed to present propagule pressure. Second, the non
      native species in this study are widely used in landscaping, and development age
      reflects the years that landscaping has been present nearby. As xeriscaping
      becomes more common, streamside woodlands may someday not have the highest non
      native species richness: the new drought-tolerant landscaping plants may be
      better invaders of drier sites than their predecessors.

PMID- 29578299
TI  - Painful grouped erythematous papules in a segmental distribution.

PMID- 29578300
TI  - Coronal Microleakage of Teeth Restored with Cast Posts and Cores Cemented with
      Four Different Luting Agents after Thermocycling.
AB  - PURPOSE: The apical seal provided by a root canal filling may be breached via
      coronal leakage. This study aimed to compare the teeth restored with custom-made
      cast metal posts and cores cemented with different luting agents in terms of
      coronal microleakage after thermocycling. MATERIALS AND METHODS: This in vitro
      study was conducted on 32 extracted single-canal teeth. Root canals were prepared
      by step-back technique and filled with gutta percha and sealer. The coronal 7 mm
      of gutta percha was removed, and post space was prepared using peeso reamers #2
      and #3 consecutively. After fabricating the acrylic resin patterns of the posts
      and cores, they were cast using Ni-Cr metal alloy. The specimens were divided
      into 4 groups in which the castings were cemented using one of the following
      luting agents: zinc phosphate (ZP), glass ionomer (GI), Panavia F 2.0, and Speed
      CEM. After cementation, the teeth were immersed in distilled water and incubated
      for 7 days. Then, the teeth were subjected to thermocycling, immersed in silver
      nitrate for 6 hours, and finally sectioned. The degree of dye penetration into
      the coronal part of the specimens was measured using a stereomicroscope. Data
      were analyzed using Kruskal-Wallis and Mann-Whitey U tests with significance
      level of 0.05. RESULTS: The median microleakage in ZP, Speed CEM, GI, and Panavia
      were 171.89, 114.76, 26.51, and 20.02 MUm, respectively. Pairwise comparisons
      among GI and ZP, GI, and Speed CEM, ZP and Panavia, ZP and Speed CEM, and Panavia
      and Speed CEM groups yielded significant differences (p < 0.05). CONCLUSION:
      Complete coronal seal was not achieved with any of the luting agents. The highest
      and the lowest degree of microleakage was yielded by ZP and Panavia luting
      agents, respectively.

PMID- 29578302
TI  - Smooth velvety hyperextensible skin in a young patient.

PMID- 29578301
TI  - Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control
      in STZ-Induced Diabetic Mice.
AB  - SCOPE: In this study, we aim to determine the effects of resveratrol (RSV) on
      muscle atrophy in streptozocin-induced diabetic mice and to explore mitochondrial
      quality control (MQC) as a possible mechanism. METHODS AND RESULTS: The
      experimental mice were fed either a control diet or an identical diet containing
      0.04% RSV for 8 weeks. Examinations were subsequently carried out, including the
      effects of RSV on muscle atrophy and muscle function, as well as on the signaling
      pathways related to protein degradation and MQC processes. The results show that
      RSV supplementation improves muscle atrophy and muscle function, attenuates the
      increase in ubiquitin and muscle RING-finger protein-1 (MuRF-1), and
      simultaneously attenuates LC3-II and cleaved caspase-3 in the skeletal muscle of
      diabetic mice. Moreover, RSV treatment of diabetic mice results in an increase in
      mitochondrial biogenesis and inhibition of the activation of mitophagy in
      skeletal muscle. RSV also protects skeletal muscle against excess mitochondrial
      fusion and fission in the diabetic mice. CONCLUSION: The results suggest that RSV
      ameliorates diabetes-induced skeletal muscle atrophy by modulating MQC.

PMID- 29578304
TI  - Anatomical strategy for complete laparoscopic mesocolic excision for splenic
      flexure colonic cancer - a video vignette.

PMID- 29578305
TI  - Yeast culture dietary supplementation modulates gut microbiota, growth and
      biochemical parameters of grass carp.
AB  - Gut microbiota contributes positively to the physiology of their host. Some feed
      additives have been suggested to improve livestock health and stimulate growth
      performance by modulating gut bacteria species. Here, we fed grass carp with 0
      (control), 8% (Treat1), 10% (Treat2), 12% (Treat3) and 16% (Treat4) of yeast
      culture (YC) for 10 weeks. The gut microbiota was analysed by 16S rRNA gene V3-4
      region via an Illumina MiSeq platform. PCoA test showed that gut bacterial
      communities in the control and Treat3 formed distinctly separate clusters.
      Although all the groups shared a large size of OTUs as a core microbiota
      community, a strong distinction existed at genus level. Treat3 contained the
      highest proportion of the beneficial bacteria and obviously enhanced the capacity
      of amino acid, lipid metabolism and digestive system. In addition, Treat3
      significantly improved the fish growth and increased the liver and serum T-SOD
      activities while dramatically decreased the liver GPT and GOT. Collectively,
      these findings demonstrate the beneficial effects of YC feeding on gut
      microbiota, growth and biochemical parameters and Treat3 might be the optimal
      supplementation amount for grass carp, which opens up the possibility that a new
      feed additive can be developed for healthy aquaculture.

PMID- 29578306
TI  - A cytotoxicity, optical spectroscopy and computational binding analysis of 4-[3
      acetyl-5-(acetylamino)-2-methyl-2,3-dihydro-1,3,4-thiadiazole-2-yl]phenyl
      benzoate in calf thymus DNA.
AB  - In this study the interaction mechanism between newly synthesized 4-(3-acetyl-5
      (acetylamino)-2-methyl-2, 3-dihydro-1,3,4-thiadiazole-2-yl) phenyl benzoate
      (thiadiazole derivative) anticancer active drug with calf thymus DNA was
      investigated by using various optical spectroscopy techniques along with
      computational technique. The absorption spectrum shows a clear shift in the lower
      wavelength region, which may be due to strong hypochromic effect in the ctDNA and
      the drug. The results of steady state fluorescence spectroscopy show that there
      is static quenching occurring while increasing the thiadiazole drug concentration
      in the ethidium bromide-ctDNA system. Also the binding constant (K), thermo
      dynamical parameters of enthalpy change (DeltaH degrees ), entropy change (DeltaS
      degrees ) Gibbs free energy change (DeltaG degrees ) were calculated at different
      temperature (293 K, 298 K) and the results are in good agreement with
      theoretically calculated MMGBSA binding analysis. Time resolved emission
      spectroscopy analysis clearly explains the thiadiazole derivative competitive
      intercalation in the ethidium bromide-ctDNA system. Further, molecular docking
      studies was carried out to understand the hydrogen bonding and hydrophobic
      interaction between ctDNA and thiadiazole derivative molecule. In addition the
      docking and molecular dynamics charge distribution analysis was done to
      understand the internal stability of thiadiazole derivative drug binding sites of
      ctDNA. The global reactivity of thiadiazole derivative such as electronegativity,
      electrophilicity and chemical hardness has been calculated.

PMID- 29578307
TI  - Rapid and simultaneous quantification of a mixture of biopharmaceuticals by a
      liquid chromatography/quadrupole time-of-flight mass spectrometric method in rat
      plasma following cassette-dosing.
AB  - RATIONALE: The cassette-dosing technique is a technique that administers various
      drugs to a single animal at once and quantitated simultaneously. The purpose of
      this study was to evaluate the feasibility of cassette-dosing as a means of
      increasing throughput and decreasing animal usage for pharmacokinetic studies of
      biopharmaceuticals using liquid chromatography/time-of-flight mass spectrometric
      (LC/TOF-MS) analysis. METHODS: Brentuximab, trastuzumab, cetuximab and adalimumab
      were used as model biopharmaceuticals. The method consisted of
      immunoprecipitation followed by tryptic digestion for sample preparation and
      LC/TOF-MS analysis of specific signature peptides in the positive ion mode using
      electrospray ionization. The specific signature peptides used for quantification
      were from the complementarity-determining regions of each mAb. All rats received
      a single intravenous bolus injection containing either a single mAb or a mixture
      of four mAbs. RESULTS: The proposed method has been qualified in linearity range
      of 1-100 MUg/mL with correlation coefficients higher than 0.990. The
      qualification run met the acceptance criteria of +/-25% accuracy and precision
      values for quality control (QC) samples. This qualified LC/TOF-MS method was
      successfully applied to a pharmacokinetic study in the rat. The PK properties of
      mAbs administered as a cassette-dosage were similar to the pharmacokinetics of
      each antibody drug when administered as a single entity. CONCLUSIONS: These
      findings suggest that the cassette-dosing approach could be used to evaluate the
      PK properties of biopharmaceuticals in the early drug discovery stage. Also, this
      method would be useful for other preclinical sample analysis without developing
      new reagents for sample preparation.

PMID- 29578308
TI  - Moderate and severe haemophilia in Spain: An epidemiological update.

PMID- 29578309
TI  - Annular paraneoplastic bullous pemphigoid mimicking linear IgA bullous dermatosis
      in a 40-year-old patient.

PMID- 29578310
TI  - Insights into Islet Differentiation and Maturation through Proteomic
      Characterization of a Human iPSC-Derived Pancreatic Endocrine Model.
AB  - PURPOSE: Great progresses have been made for generating in vitro pluripotent stem
      cell pancreatic beta-like cells. However, the maturation stage of the cells still
      requires in vivo maturation to recreate the environmental niche. A deeper
      understanding of the factors promoting maturation of the cells is of great
      interest for clinical applications. EXPERIMENTAL DESIGN: Label-free mass
      spectrometry based proteomic analysis is performed on samples from a longitudinal
      study of differentiation of human induced pluripotent stem cells toward glucose
      responsive insulin producing cells. RESULTS: Proteome patterns correlate with
      specific transcription factor gene expression levels during in vitro
      differentiation, showing the relevance of the technology for identification of
      pancreatic-specific markers. The analysis of proteomes of the implanted cells in
      a longitudinal study shows that the neovascularization process linked to the
      extracellular matrix environment is time-dependent and conditions the proper
      maturation of the cells in beta-like cells secreting insulin in response to
      glucose. CONCLUSIONS AND CLINICAL RELEVANCE: Proteomic profiling is valuable to
      qualify and better understand in vivo maturation of progenitor cells toward beta
      cells. This is critical for future clinical trials where in vivo maturation still
      needs to be improved for robustness and effectiveness of cell therapy. Novel
      biomarkers for predicting the efficiency of maturation represents noninvasive
      monitoring tools for following efficiency of the implant.

PMID- 29578311
TI  - Correlates of toenail selenium and its cross-sectional association with metabolic
      syndrome.
AB  - BACKGROUND: The present study aimed to identify independent correlates of toenail
      selenium levels and to examine the association between toenail selenium levels
      and metabolic syndrome in Korean adults. METHODS: Cross-sectional analysis was
      conducted using baseline data from the Trace Element Study of Korean Adults in
      the Yeungnam area, an ongoing cohort study of Korean adults over the age of 35
      years. The baseline survey consisted of questionnaires on demographics, lifestyle
      characteristics and medical information. Dietary information was obtained through
      a validated semi-quantitative food frequency questionnaire. Toenail selenium
      levels were quantified using neutron activation analysis. Biomarkers associated
      with metabolic syndrome were obtained from biennial medical check-ups. RESULTS:
      In the multivariable-adjusted analyses, independent lifestyle and dietary
      correlates of higher selenium levels were alcohol drinking (4.62% higher than
      nondrinking) and egg intake (0.43% higher per weekly serving), whereas current
      smoking (5.42% lower than nonsmoking) and vegetable consumption (0.05% lower per
      weekly serving) were associated with lower toenail selenium levels. In the
      multivariable adjusted logistic regression, no significant association was
      observed between toenail selenium levels and metabolic syndrome (odds ratio =
      1.33, 95% confidence interval = 0.58-3.05). CONCLUSIONS: Multiple lifestyle and
      dietary factors influenced toenail selenium levels, although no meaningful
      association was observed between toenail selenium levels and metabolic syndrome
      in Korean adults. Future prospective large-scale cohort studies are required to
      determine whether there is a causal relationship between selenium levels and
      metabolic syndrome in Korean adults.

PMID- 29578312
TI  - Group-specific environmental sequencing reveals high levels of ecological
      heterogeneity across the microsporidian radiation.
AB  - The description of diversity is a key imperative in current biological studies
      and has been revolutionised by the molecular era that allows easy access to
      microbial diversity not visible to the naked eye. Broadly targeted SSU rRNA gene
      amplicon studies of diverse environmental habitats continue to reveal new
      microbial eukaryotic diversity. However, some eukaryotic lineages, particularly
      parasites, have divergent SSU sequences, and are therefore undersampled or
      excluded by the methodologies used for SSU studies. One such group is the
      Microsporidia, which have particularly divergent SSU sequences and are rarely
      detected in even large-scale amplicon studies. This is a serious omission as
      microsporidia are diverse and important parasites of humans and other animals of
      socio-economic importance. Whilst estimates of other microbial diversity are
      expanding, our knowledge of true microsporidian diversity has remained largely
      static. In this work, we have combined high throughput sequencing, broad
      environmental sampling and microsporidian-specific primers to broaden our
      understanding of the evolutionary diversity of the Microsporidia. Mapping our new
      sequences onto a tree of known microsporidian diversity we uncover new diversity
      across all areas of the microsporidian tree and uncover clades dominated by novel
      sequences, with no close described relatives.

PMID- 29578313
TI  - "In vitro" correction of the severe factor V deficiency-related coagulopathy by a
      novel plasma-derived factor V concentrate.
AB  - INTRODUCTION: Severe congenital factor V (FV) deficiency is a rare bleeding
      disorder characterized by very low/undetectable levels of FV. Fresh frozen plasma
      is the standard treatment for bleeding manifestations. Recently, a novel plasma
      derived FV concentrate has been developed. AIM: To evaluate the "in vitro"
      ability of the novel FV concentrate to normalize clotting times and generate
      normal amount of thrombin in plasma collected from patients with severe FV
      deficiency. METHODS: Prothrombin time (PT), activated partial thromboplastin time
      (aPTT), FV activity and antigen levels and thrombin generation were measured pre-
      and postspiking of plasma samples of 10 patients with increasing doses of FV
      concentrate (from 0 to 100 IU/dL). RESULTS: Prothrombin time and activated
      partial thromboplastin time ratios as well as all thrombin generation parameters
      were fully corrected by the addition of FV concentrate at a final concentration
      of 25 IU/dL. However, the addition of FV at a concentration of 1-3 IU/dL was
      already sufficient to correct peak height and endogenous thrombin potential (but
      not lag time and time to peak) after activation with 5 pmol/L tissue factor. FV
      activity and antigen levels showed a linear response to supplementation with the
      novel FV concentrate. CONCLUSION: The novel plasma-derived FV concentrate was
      effective to correct "in vitro" severe FV deficiency in patients. The optimal FV
      concentration to fully normalize both global clotting times and thrombin
      generation parameters using the novel plasma-derived FV concentrate was 25 IU/dL.

PMID- 29578315
TI  - Genes involved in stress response influence lithium efficacy in bipolar patients.
AB  - OBJECTIVES: In mood disorders, chronic stimulation with stress results in
      aberrant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Lithium was
      shown to influence HPA axis function. The underlying genetic background as well
      as environmental context may influence the stress response, and therefore lithium
      efficacy. The aim of the present study was to analyze if genetic variants located
      in genes involved in HPA axis regulation affect the response to long-term lithium
      treatment in bipolar patients. METHODS: We included 93 patients with bipolar
      disorder (32 males and 61 females), aged 31-80 years. The patients had been
      treated with lithium carbonate for at least 5 years. The magnitude of the lithium
      response was assessed using the Alda scale. Genotyping was performed for 28
      polymorphisms in the genes encoding the following proteins involved in HPA axis
      regulation: corticotropin-releasing hormone receptor 1 (CRHR1), arginine
      vasopressin receptor 1B (AVPR1b), FK506 binding protein (FKBP) 5, FKBP4, BCL2
      associated athanogene 1 (BAG1), stress induced phosphoprotein 1 (STIP1),
      glucocorticoid-induced transcript 1 (GLCC1), dual specificity phosphatase 1
      (DUSP1) serine and arginine rich splicing factor (SRSF) 3, SRSF9, SRSF5, and acid
      phosphatase 1 (ACP1). Linkage disequilibrium and haplotype analysis were then
      performed, followed by statistical analysis (Statistica v.12; Stasoft, Krakow,
      Poland). RESULTS: We found a correlation between stressful life events at first
      episode and worse response to lithium (P=.019). In single marker analysis, we
      observed a significant association between three FKBP5 polymorphisms (rs1360780,
      rs7748266 and rs9296158), one ACP1 variant (rs300774) and one glucocorticoid
      induced transcript 1 gene (GLCC1) variant (rs37972) and the degree of lithium
      response. Five out of seven FKBP5 polymorphisms showed strong linkage with one
      haplotype demonstrating an association with lithium efficacy (P=.008). No
      relationship was found between the other analyzed polymorphisms and lithium
      response. CONCLUSION: The response to lithium may depend on the variants of genes
      regulating the HPA axis and stressful life events in bipolar patients.

PMID- 29578314
TI  - Aspiring personality: Patients waiting for obesity treatment.
AB  - The aim of the present study was to investigate differences in temperament and
      character between patients (N = 70) waiting for obesity surgery and the general
      population. Patients waiting for obesity surgery scored higher in Harm-Avoidance,
      Reward Dependence, Persistence, and Cooperativeness and also lower in Self
      Directedness.

PMID- 29578316
TI  - Exploring Orthogonal Hydrogen Bonding towards Designing Organic-Salt-Based
      Supramolecular Gelators: Synthesis, Structures, and Anticancer Properties.
AB  - A series of primary ammonium monocarboxylate (PAM) salts derived from beta
      alanine derivatives of pyrene and naphthalene acetic acid, along with the parent
      acids, were explored to probe the plausible role of orthogonal hydrogen bonding
      resulting from amide???amide and PAM synthons on gelation. Single-crystal X-ray
      diffraction (SXRD) studies were performed on two parent acids and five PAM salts
      in the series. The data revealed that orthogonal hydrogen bonding played an
      important role in gelation. Structure-property correlation based on SXRD and
      powder X-ray diffraction data also supported the working hypothesis upon which
      these gelators were designed. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) and cell migration assay on a highly aggressive
      human breast cancer cell line, MDA-MB-231, revealed that one of the PAM salts in
      the series, namely, PAA.B2, displayed anticancer properties, and internalization
      of the gelator salt in the same cell line was confirmed by cell imaging.

PMID- 29578317
TI  - Least median of squares and iteratively re-weighted least squares as robust
      linear regression methods for fluorimetric determination of alpha-lipoic acid in
      capsules in ideal and non-ideal cases of linearity.
AB  - This study outlines two robust regression approaches, namely least median of
      squares (LMS) and iteratively re-weighted least squares (IRLS) to investigate
      their application in instrument analysis of nutraceuticals (that is, fluorescence
      quenching of merbromin reagent upon lipoic acid addition). These robust
      regression methods were used to calculate calibration data from the fluorescence
      quenching reaction (?F and F-ratio) under ideal or non-ideal linearity
      conditions. For each condition, data were treated using three regression
      fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity,
      limits of detection (LOD) and quantitation (LOQ), accuracy and precision were
      carefully studied for each condition. LMS and IRLS regression line fittings
      showed significant improvement in correlation coefficients and all regression
      parameters for both methods and both conditions. In the ideal linearity
      condition, the intercept and slope changed insignificantly, but a dramatic change
      was observed for the non-ideal condition and linearity intercept. Under both
      linearity conditions, LOD and LOQ values after the robust regression line fitting
      of data were lower than those obtained before data treatment. The results
      obtained after statistical treatment indicated that the linearity ranges for drug
      determination could be expanded to lower limits of quantitation by enhancing the
      regression equation parameters after data treatment. Analysis results for lipoic
      acid in capsules, using both fluorimetric methods, treated by parametric OLS and
      after treatment by robust LMS and IRLS were compared for both linearity
      conditions.

PMID- 29578318
TI  - Nitrogen gene regulation in environmental microbes: An annotated selection of
      World Wide Web sites relevant to the topics in environmental microbiology.

PMID- 29578319
TI  - Corrigendum: Gate-Voltage Control of Borophene Structure Formation.

PMID- 29578320
TI  - Corrigendum: A Membrane-Free Redox Flow Battery with Two Immiscible Redox
      Electrolytes.

PMID- 29578321
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 15/2018.

PMID- 29578322
TI  - Towards actionable health information: the expanding armory of laboratory cancer
      diagnostics.

PMID- 29578323
TI  - House Dust Endotoxin Association with Chronic Bronchitis and Emphysema.
AB  - BACKGROUND: Endotoxin has been reported to be associated with chronic bronchitis
      or emphysema (CBE) at high occupational exposures. However, whether levels found
      in domestic environments have similar effects is unknown. OBJECTIVES: We aimed to
      study the association between house dust endotoxin and CBE in a sample
      representative of the U.S. population. METHODS: We analyzed data from 3,393
      participants >=20 y old from the National Health and Nutrition Examination Survey
      (NHANES) 2005-2006. House dust from bedding and from bedroom floors was analyzed
      for endotoxin content. NHANES participants received questionnaires and underwent
      examination as well as extensive laboratory testing. Logistic regression was used
      to examine the association of endotoxin levels with CBE diagnosis and symptoms,
      adjusting for covariates. The survey design and weights were applied so that
      estimates were nationally representative and so that statistical inferences were
      made appropriately. RESULTS: The median endotoxin concentration in house dust was
      14.61 EU/mg dust, and CBE was reported by 8.2% of participants. In the adjusted
      analysis, one unit (EU/mg) increase in log10-transformed endotoxin concentrations
      was associated with a 27% increase in the odds of CBE diagnosis [OR=1.27 (95% CI:
      1.00, 1.61)] and a 78% increase in the odds of chronic bronchitis symptoms
      (defined as cough and phlegm for >=3 mo in a year for >=2 y) [OR=1.78 (95% CI:
      1.01, 3.12)]. Sensitization to inhalant allergens (p=0.001) modified the
      relationship between endotoxin and CBE diagnosis, with stronger associations
      observed in sensitized participants [OR=2.46 (95% CI: 1.72, 3.50) for a unit
      increase in log10-endotoxin]. CONCLUSIONS: In a population-based sample of U.S.
      adults, endotoxin levels in homes were associated with a self-reported history of
      CBE diagnosis and chronic bronchitis symptoms, with stronger associations among
      people sensitized to inhalant allergens. https://doi.org/10.1289/EHP2452.

PMID- 29578324
TI  - Boosting Visible Light Absorption of Metal-Oxide-Based Phototransistors via
      Heterogeneous In-Ga-Zn-O and CH3NH3PbI3 Films.
AB  - To broaden the availability and application of metal-oxide (M-O)-based
      optoelectronic devices, we suggest heterogeneous phototransistors composed of In
      Ga-Zn-O (IGZO) and methylammonium lead iodide (CH3NH3PbI3) layers, which act as
      the amplifier layer (channel layer) and absorption layer, respectively. These
      heterogeneous phototransistors showed low persistence photocurrent compared with
      IGZO-only phototransistors and exhibited high photoresponsivity of 61 A/W,
      photosensitivity of 3.48 * 106, detectivity of 9.42 * 1010 Jones, external
      quantum efficiency of 154% in an optimized structure, and high photoresponsivity
      under water exposure via the deposition of silicon dioxide as a passivation
      layer. On the basis of these electrical results and various analyses, we
      determined that CH3NH3PbI3 could be activated as a light absorption layer,
      current barrier, and plasma damage blocking layer, which would serve to widen the
      range of applications of M-O-based optoelectronic devices with high
      photoresponsivity and reliability under visible light illumination.

PMID- 29578325
TI  - High-Sensitivity and Low-Power Flexible Schottky Hydrogen Sensor Based on Silicon
      Nanomembrane.
AB  - High-performance and low-power flexible Schottky diode-based hydrogen sensor was
      developed. The sensor was fabricated by releasing Si nanomembrane (SiNM) and
      transferring onto a plastic substrate. After the transfer, palladium (Pd) and
      aluminum (Al) were selectively deposited as a sensing material and an electrode,
      respectively. The top-down fabrication process of flexible Pd/SiNM diode H2
      sensor is facile compared to other existing bottom-up fabricated flexible gas
      sensors while showing excellent H2 sensitivity (Delta I/ I0 > 700-0.5% H2
      concentrations) and fast response time (tau10-90 = 22 s) at room temperature. In
      addition, selectivity, humidity, and mechanical tests verify that the sensor has
      excellent reliability and robustness under various environments. The operating
      power consumption of the sensor is only in the nanowatt range, which indicates
      its potential applications in low-power portable and wearable electronics.

PMID- 29578326
TI  - Three-Dimensional Orientation of Anisotropic Plasmonic Aggregates at
      Intracellular Nuclear Indentation Sites by Integrated Light Sheet Super
      Resolution Microscopy.
AB  - Three-dimensional (3D) orientations of individual anisotropic plasmonic
      nanoparticles in aggregates were observed in real time by integrated light sheet
      super-resolution microscopy ( iLSRM). Asymmetric light scattering of a gold
      nanorod (AuNR) was used to trigger signals based on the polarizer angle.
      Controlled photoswitching was achieved by turning the polarizer and obtaining a
      series of images at different polarization directions. 3D subdiffraction-limited
      super-resolution images were obtained by superlocalization of scattering signals
      as a function of the anisotropic optical properties of AuNRs. Varying the
      polarizer angle allowed resolution of the orientation of individual AuNRs. 3D
      images of individual nanoparticles were resolved in aggregated regions, resulting
      in as low as 64 nm axial resolution and 28 nm spatial resolution. The proposed
      imaging setup and localization approach demonstrates a convenient method for
      imaging under a noisy environment where the majority of scattering noise comes
      from cellular components. This integrated 3D iLSRM and localization technique was
      shown to be reliable and useful in the field of 3D nonfluorescence super
      resolution imaging.

PMID- 29578327
TI  - Metallic Ni3S2 Films Grown by Atomic Layer Deposition as an Efficient and Stable
      Electrocatalyst for Overall Water Splitting.
AB  - We describe the direct preparation of crystalline Ni3S2 thin films via atomic
      layer deposition (ALD) techniques at temperatures as low as 250  degrees C
      without postthermal treatments. A new ALD chemistry is proposed using bis(1
      dimethylamino-2-methyl-2-butoxy) nickel(II) [Ni(dmamb)2] and H2S as precursors.
      Homogeneous and conformal depositions of Ni3S2 films were achieved on 4 in.
      wafers (both metal and oxide substrates, including Au and SiO2). The resulting
      crystalline Ni3S2 layers exhibited highly efficient and stable performance as
      electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen
      evolution reaction (OER) in alkaline solutions, with a low overpotential of 300
      mV and a high turnover frequency for HER and an overpotential of 400 mV for OER
      (at a current density of 10 mA/cm2). Using our Ni3S2 films as both the cathode
      and the anode, two-electrode full-cell electrolyzers were constructed, which
      showed stable operation for 100 h at a current density of 10 mA/cm2. The proposed
      ALD electrocatalysts on planar surfaces exhibited the best performance among
      Ni3S2 materials for overall water splitting recorded to date.

PMID- 29578329
TI  - Temperature-Dependent and Gate-Tunable Rectification in a Black Phosphorus/WS2
      van der Waals Heterojunction Diode.
AB  - Heterostructures comprising two-dimensional (2D) semiconductors fabricated by
      individual stacking exhibit interesting characteristics owing to their 2D nature
      and atomically sharp interface. As an emerging 2D material, black phosphorus (BP)
      nanosheets have drawn much attention because of their small band gap
      semiconductor characteristics along with high mobility. Stacking structures
      composed of p-type BP and n-type transition metal dichalcogenides can produce an
      atomically sharp interface with van der Waals interaction which leads to p-n
      diode functionality. In this study, for the first time, we fabricated a
      heterojunction p-n diode composed of BP and WS2. The rectification effects are
      examined for monolayer, bilayer, trilayer, and multilayer WS2 flakes in our
      BP/WS2 van der Waals heterojunction diodes and also verified by density function
      theory calculations. We report superior functionalities as compared to other van
      der Waals heterojunction, such as efficient gate-dependent static rectification
      of 2.6 * 104, temperature dependence, thickness dependence of rectification, and
      ideality factor of the device. The temperature dependence of Zener breakdown
      voltage and avalanche breakdown voltage were analyzed in the same device.
      Additionally, superior optoelectronic characteristics such as photoresponsivity
      of 500 mA/W and external quantum efficiency of 103% are achieved in the BP/WS2
      van der Waals p-n diode, which is unprecedented for BP/transition metal
      dichalcogenides heterostructures. The BP/WS2 van der Waals p-n diodes have a
      profound potential to fabricate rectifiers, solar cells, and photovoltaic diodes
      in 2D semiconductor electronics and optoelectronics.

PMID- 29578328
TI  - Local Conduction in Mo xW1- xSe2: The Role of Stacking Faults, Defects, and
      Alloying.
AB  - Here, we report on the surface conductivity of WSe2 and Mo xW1- xSe2 (0 <= x <=
      1) crystals investigated with conductive atomic force microscopy. We found that
      stacking faults, defects, and chemical heterogeneities form distinct two
      dimensional and one-dimensional conduction paths on the transition metal
      dichalcogenide surface. In the case of WSe2, in addition to step edges, we find a
      significant amount of stacking faults (formed during the cleaving process) that
      strongly influence the surface conductivity. These regions are attributed to the
      alternation of the 2H and 3R polytypism. The stacking faults form regular 2D
      patterns by alternation of the underlying stacking order, with a periodicity that
      varies significantly between different regions and samples. In the case of Mo xW1
      xSe2, its conductivity has a localized nature, which depends on the underlying
      chemical composition and the Mo/W ratio. Segregation to W-rich and Mo-rich
      regions during the growth process leads to nonuniform conduction paths on the
      surface of the alloy. We found a gradual change of the conductivity moving from
      one region to the other, reminiscent of lateral band bending. Our results
      demonstrate the use of C-AFM as a nanoscopic tool to probe the electrical
      properties of largely inhomogeneous samples and show the complicated nature of
      the surface conductivity of TMDC alloys.

PMID- 29578330
TI  - FESTA: An Efficient Nuclear Magnetic Resonance Approach for the Structural
      Analysis of Mixtures Containing Fluorinated Species.
AB  - In complex mixtures, proton nuclear magnetic resonance (NMR) spectra are often
      very crowded, making spectral analysis complicated or even impossible,
      particularly when detailed structural information about the mixture components is
      needed. A new 1D NMR method (fluorine-edited selective TOCSY acquisition, FESTA)
      is introduced that facilitates the structural analysis of mixtures of species
      that contain fluorine. It allows simplified 1H spectra to be obtained that show
      only those protons that are in a spin system coupled to fluorine of interest. The
      new method is illustrated by factorizing a complex 1H spectrum into subspectra
      for individual spin systems involving different 19F sites.

PMID- 29578331
TI  - Disposable MoS2-Arrayed MALDI MS Chip for High-Throughput and Rapid
      Quantification of Sulfonamides in Multiple Real Samples.
AB  - In this work, we demonstrate, for the first time, the development of a disposable
      MoS2-arrayed matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) chip combined with an immunoaffinity enrichment method for high-throughput,
      rapid, and simultaneous quantitation of multiple sulfonamides (SAs). The
      disposable MALDI MS chip was designed and fabricated by MoS2 array formation on a
      commercial indium tin oxide (ITO) glass slide. A series of SAs were analyzed, and
      clear deprotonated signals were obtained in negative-ion mode. Compared with MoS2
      arrayed commercial steel plate, the prepared MALDI MS chip exhibited comparable
      LDI efficiency, providing a good alternative and disposable substrate for MALDI
      MS analysis. Furthermore, internal standard (IS) was previously deposited onto
      the MoS2 array to simplify the experimental process for MALDI MS quantitation. 96
      sample spots could be analyzed within 10 min in one single chip to perform
      quantitative analysis, recovery studies, and real foodstuff detection. Upon
      targeted extraction and enrichment by antibody conjugated magnetic beads, five
      SAs were quantitatively determined by the IS-first method with the linear range
      of 0.5-10 ng/mL ( R2 > 0.990). Good recoveries and repeatability were obtained
      for spiked pork, egg, and milk samples. SAs in several real foodstuffs were
      successfully identified and quantified. The developed method may provide a
      promising tool for the routine analysis of antibiotic residues in real samples.

PMID- 29578332
TI  - Turning Earth Abundant Kesterite-Based Solar Cells Into Efficient Protected Water
      Splitting Photocathodes.
AB  - CZTS/Se kesterite-based solar cells have been protected by conformal atomic layer
      deposition (ALD)-deposited TiO2 demonstrating its feasibility as powerful
      photocathodes for water splitting in highly acidic conditions (pH < 1), achieving
      stability with no detected degradation and with current density levels similar to
      photovoltaic productivities. The ALD has allowed low deposition temperatures of
      200  degrees C for TiO2, preventing significant variations to the kesterite
      structure and CdS heterojunction, except for the pure-sulfide stoichiometry,
      which was studied by Raman spectroscopy. The measured photocurrent at 0 V vs
      reversible hydrogen electrode, 37 mA.cm-2, is the highest reported to date, and
      the associated half-cell solar-to-hydrogen efficiency reached 7%, being amongst
      the largest presented for kesterite-based photocathodes, corroborating the
      possibility of using them as abundant low-cost alternative photoabsorbers as
      their efficiencies are improved toward those of chalcopyrites. An electrical
      circuit has been proposed to model the photocathode, which comprises the photon
      absorption, charge transfer through the protective layer, and catalytic
      performance, which paves the way to the design of highly efficient
      photoelectrodes.

PMID- 29578333
TI  - Charged Residues in the C-Terminal Domain of Apolipoprotein A-I Modulate
      Oligomerization.
AB  - Charged residues of the C-terminal domain of human apolipoprotein A-I (apoA-I)
      were targeted by site-directed mutagenesis. A series of mutant proteins was
      engineered in which lysine residues (Lys 195, 206, 208, 226, 238, and 239) or
      glutamate residues (Glu 234 and 235) were replaced by glutamine. The amino acid
      substitutions did not result in changes in secondary structure content or protein
      stability. Cross-linking and size-exclusion chromatography showed that the
      mutations resulted in reduced self-association, generating a predominantly
      monomeric apoA-I when five or six lysine residues were substituted. The rate of
      phosphatidylcholine vesicle solubilization was enhanced for all variants, with
      approximately a threefold rate enhancement for apoA-I lacking Lys 206, 208, 238,
      and 239, or Glu 234 and 235. Single or double mutations did not change the
      ability to protect lipolyzed low density lipoprotein from aggregation, but
      variants lacking >4 lysine residues were less effective in preventing lipoprotein
      aggregation. ApoA-I mediated cellular lipid efflux from wild-type mice macrophage
      foam cells was decreased for the variant with five lysine mutations. However,
      this protein was more effective in releasing cellular phosphatidylcholine and
      sphingomyelin from Abca1-null mice macrophage foam cells. This suggests that the
      mutations caused changes in the interaction with ABCA1 transporters and that
      membrane microsolubilization was primarily responsible for lipid efflux in cells
      lacking ABCA1. Taken together, this study indicates that ionic interactions in
      the C-terminal domain of apoA-I favor self-association and that monomeric apoA-I
      is more active in solubilizing phospholipid bilayers.

PMID- 29578334
TI  - Cytidine Diphosphoramidate Kinase: An Enzyme Required for the Biosynthesis of the
      O-Methyl Phosphoramidate Modification in the Capsular Polysaccharides of
      Campylobacter jejuni.
AB  - Campylobacter jejuni, a leading cause of gastroenteritis, produces a capsular
      polysaccharide that is derivatized with a unique O-methyl phosphoramidate (MeOPN)
      modification. This modification contributes to serum resistance and invasion of
      epithelial cells. Previously, the first three biosynthetic steps for the
      formation of MeOPN were elucidated. The first step is catalyzed by a novel
      glutamine kinase (Cj1418), which catalyzes the adenosine triphosphate (ATP)
      dependent phosphorylation of the amide nitrogen of l-glutamine. l-Glutamine
      phosphate is used by cytidine triphosphate (CTP):phosphoglutamine
      cytidylyltransferase (Cj1416) to displace pyrophosphate from CTP to generate
      cytidine diphosphate (CDP)-l-glutamine, which is then hydrolyzed by gamma
      glutamyl-CDP-amidate hydrolase (Cj1417) to form cytidine diphosphoramidate (CDP
      NH2). Here, we show that Cj1415 catalyzes the ATP-dependent phosphorylation of
      CDP-NH2 to form 3'-phospho-cytidine-5'-diphosphoramidate. Cj1415 will also
      catalyze the phosphorylation of adenosine diphosphoramidate (ADP-NH2) and uridine
      diphosphoramidate (UDP-NH2) but at significantly reduced rates. It is proposed
      that Cj1415 be named cytidine diphosphoramidate kinase.

PMID- 29578335
TI  - Micropatterned 2D Hybrid Perovskite Thin Films with Enhanced Photoluminescence
      Lifetimes.
AB  - The application of luminescent materials in display screens and devices requires
      micropatterned structures. In this work, we have successfully printed
      microstructures of a two-dimensional (2D), orange-colored organic/inorganic
      hybrid perovskite ((C6H5CH2NH3)2PbI4) using two different soft lithography
      techniques. Notably, both techniques yield microstructures with very high aspect
      ratios in the range of 1.5-1.8. X-ray diffraction reveals a strong preferential
      orientation of the crystallites along the c-axis in both patterned structures,
      when compared to nonpatterned, drop-casted thin films. Furthermore, (time
      resolved) photoluminescence (PL) measurements reveal that the optical properties
      of (C6H5CH2NH3)2PbI4 are conserved upon patterning. We find that the larger grain
      sizes of the patterned films with respect to the nonpatterned film give rise to
      an enhanced PL lifetime. Thus, our results demonstrate easy and cost-effective
      ways to manufacture patterns of 2D organic/inorganic hybrid perovskites, while
      even improving their optical properties. This demonstrates the potential use of
      color-tunable 2D hybrids in optoelectronic devices.

PMID- 29578336
TI  - Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin by
      Cleaving Its Ansa-Bridge.
AB  - Rifampicin monooxygenase (RIFMO) decreases the potency of rifampicin (RIF) by
      converting it to oxidative products. Further decomposition of RIF has been
      observed in bacteria producing RIFMO and contributes to RIFMO-mediated drug
      resistance. Here we report the first crystal structure of RIFMO in complex with
      the hydroxylated RIF product. The 2.10 A resolution structure reveals a breach of
      the ansa aliphatic chain of RIF between naphthoquinone C2 and amide N1. Our data
      suggest that RIFMO catalyzes the hydroxylation of RIF at the C2 atom followed by
      cleavage of the ansa linkage, which leads to inactivation of the antibiotic by
      preventing key contacts with the RNA polymerase target.

PMID- 29578337
TI  - Investigating the Effect of Bioirrigation on In Situ Porewater Concentrations and
      Fluxes of Polychlorinated Biphenyls Using Passive Samplers.
AB  - Polychlorinated biphenyl (PCB) fluxes from contaminated sediments can be caused
      by mechanisms including diffusion, bioirrigation, and resuspension, but it is
      often unclear which mechanisms are important. In the Lower Duwamish Waterway
      (Seattle, Washington), the presence of abundant benthic macrofauna suggests that
      porewater bioirrigation may be an important mechanism for PCB transport from the
      bed into the overlying water column. In this field study, the fluxes of PCBs due
      to bioirrigation were quantified by using (a) polyethylene (PE) samplers to
      quantify in situ and ex situ (i.e., equilibrium) PCB porewater concentration
      profiles and (b) measurements of the geochemical tracer 222Rn to quantify the
      rate of porewater exchange with overlying water. The results showed that
      bioirrigation caused sorptive disequilibrium with the surrounding sediment, which
      led to lower in situ porewater concentrations than expected from sediment
      concentrations. The combined fluxes of seven PCB congeners (Sigma7PCBs) were 1.6
      26 ng/m2/day for the three field sites, similar in magnitude to the upper limit
      estimates of diffusive fluxes calculated assuming water-side boundary layer
      control (Sigma7PCBs = 1.3-47 ng/m2/day). Moreover, the depleted in situ porewater
      concentrations imply lower diffusive flux estimates than if the ex situ porewater
      concentrations had been used to estimate fluxes (Sigma7PCBs = 89-670 ng/m2/day).
      These results suggest that nondiffusive PCB fluxes from the sediment bed are
      occurring and that quantifying in situ porewater concentrations is crucial for
      accurately quantifying both diffusive and nondiffusive PCB fluxes.

PMID- 29578338
TI  - Exploration of the Kinetics of Toehold-Mediated Strand Displacement via Plasmon
      Rulers.
AB  - DNA/RNA strand displacement is one of the most fundamental reactions in DNA and
      RNA circuits and nanomachines. In this work, we reported an exploration of the
      dynamic process of the toehold-mediated strand displacement via core-satellite
      plasmon rulers at the single-molecule level. Applying plasmon rulers with
      unlimited lifetime, single-strand displacement triggered by the invader that
      resulted in stepwise leaving of satellite from the core was continuously
      monitored by changes of scattering signal for hours. The kinetics of strand
      displacement in vitro with three different toehold lengths have been
      investigated. Also, the study revealed the difference in the kinetics of strand
      displacement between DNA/RNA and DNA/DNA duplexes. For the kinetics study in
      vivo, influence from the surrounding medium has been evaluated using both
      phosphate buffer and cell lysate. Applying core-satellite plasmon rulers with
      high signal/noise ratio, kinetics study in living cells proceeded for the first
      time, which was not possible by conventional methods with a fluorescent reporter.
      The plasmon rulers, which are flexible, easily constructed, and robust, have
      proven to be effective tools in exploring the dynamical behaviors of biochemical
      reactions in vivo.

PMID- 29578339
TI  - CsFe4-deltaSe4: A Compound Closely Related to Alkali-Intercalated FeSe
      Superconductors.
AB  - We report the synthesis and characterizations of a new FeSe-based compound CsFe4
      deltaSe4, which is closely related to alkali intercalated FeSe superconductors
      while exhibits distinct features. It does not undergo phase separation and
      antiferromagnetic transition. Powder neutron diffractions, electron microscopy
      and high-angle annular-dark-field images confirm that CsFe4-deltaSe4 possesses an
      ordered Cs arrangement as ?2 * ?2 superstructure, evidencing a B-centered
      orthorhombic lattice with a space group of Bmmm. The temperature-dependent powder
      neutron diffractions indicate no structural and magnetic transition from 320 to 5
      K. In contrast to the symmetry-breaking in FeSe, this phase naturally possesses
      the orthorhombic symmetry even at room temperature. DFT calculations and
      transport measurements reveal a novel Fermi surface geometry with two electron
      like sheets centered on Gamma point and intermediate density of states at the
      Fermi level comparing with the value of FeSe and the superconducting A xFe2Se2.

PMID- 29578340
TI  - Base-Independent DNA Base-Excision Repair of 8-Oxoguanine.
AB  - Living organisms protect their genome from gene mutation by excising damaged DNA
      bases. Here, 8-oxoguanine (8OG) is one of the most abundant DNA lesions. In
      bacteria the base excision is catalyzed by the enzyme formamidopyrimidine-DNA-
      glycosylase (Fpg), for which two different orientations of 8OG binding into the
      active site of Fpg have been proposed: syn- and anti-conformation. Here, we
      present a new ribose-protonated repair mechanism for 8OG that is base-independent
      and can excise 8OG in both conformations. Using high-level QM/MM calculations
      with up to 588/573 atoms in the QM sphere, the activation barrier is computed in
      excellent agreement with the experimentally measured value. Since the excised
      base itself is not directly involved in the mechanism, this implies that lesion
      discrimination does not occur within the active site of the enzyme.

PMID- 29578341
TI  - Size-, Shape-, and Composition-Dependent Model for Metal Nanoparticle Stability
      Prediction.
AB  - Although tremendous applications for metal nanoparticles have been found in
      modern technologies, the understanding of their stability as related to
      morphology (size and shape) and chemical ordering (e.g., in bimetallics) remains
      limited. First-principles methods such as density functional theory (DFT) are
      capable of capturing accurate nanoalloy energetics; however, they are limited to
      very small nanoparticle sizes (<2 nm in diameter) due to their computational
      cost. Herein, we propose a bond-centric (BC) model able to capture cohesive
      energy trends over a range of monometallic and bimetallic nanoparticles and
      mixing behavior (excess energy) of nanoalloys, in great agreement with DFT
      calculations. We apply the BC model to screen the energetics of a recently
      reported 23 196-atom FePt nanoalloys ( Yang et al. Nature 2017 , 542 , 75 - 79 ),
      offering insights into both segregation and bulk-chemical ordering behavior.
      Because the BC model utilizes tabulated data (diatomic bond energies and bulk
      cohesive energies) and structural information on nanoparticles (coordination
      numbers), it can be applied to calculate the energetics of any nanoparticle
      morphology and chemical composition, thus significantly accelerating nanoalloy
      design.

PMID- 29578342
TI  - Isolation, Characterization, and Structure-Activity Relationship Analysis of
      Abietane Diterpenoids from Callicarpa bodinieri as Spleen Tyrosine Kinase
      Inhibitors.
AB  - Species belonging to the genus Callicarpa are used traditionally in Chinese
      medicine for the treatment of inflammation, rheumatism, and pain. Investigation
      of the leaves and twigs of Callicarpa bodinieri resulted in the isolation of nine
      new abietane diterpenoids, bodinieric acids A-I (1-9), along with six known
      compounds (10-15). The structures of 1-9 were elucidated on the basis of the
      interpretation of their HRESIMS and NMR data and by ECD calculations. To explore
      the potential therapeutic target of this plant for immune-mediated disease, the
      inhibitory activities of the isolates obtained were determined against 13 kinase
      enzymes. Eight compounds exhibited moderate inhibitory effects on spleen tyrosine
      kinase (SYK), and the IC50 values of compounds 2 and 6 were 7.2 and 10.7 MUM,
      respectively. In addition, a preliminary structure-activity relationship of this
      scaffold was analyzed with both molecular docking and a 3D-QSAR pharmacophore
      model.

PMID- 29578344
TI  - Effects of High Acidity on Phase Transitions of an Organic Aerosol.
AB  - Aerosol particle morphology influences the effect of particles on climate. Recent
      studies have documented the high acidity found in many ambient aerosol particles.
      The effect of this acidity on the phase transitions of mixed organic/inorganic
      aerosol particles has not been addressed. To investigate this effect, six organic
      compounds and ammonium sulfate were investigated individually with varying
      amounts of sulfuric acid to determine the role of low pH in the separation,
      efflorescence, and deliquescence transitions. All phase transitions were affected
      by the addition of sulfuric acid. This effect was attributed primarily to the
      change in the identity of the inorganic component as the ammonium/sulfate ratio
      (ASR) was changed from 2 to 1.5 to 1. The separation relative humidity (SRH)
      decreased with increasing amounts of sulfuric acid for each system studied, with
      the largest effect seen in compounds that have a lower SRH when mixed with
      ammonium sulfate. Control studies without an inorganic salt revealed that for
      some systems, phase separation occurs for mixtures of sulfuric acid and an
      organic acid. Overall, it was found that for aerosol particles at low pH (<=0.35)
      composed of organic acids and inorganic salts, phase separation can be impeded in
      some cases.

PMID- 29578343
TI  - Human beta-Defensin 1 and beta-Defensin 3 (Mouse Ortholog mBD14) Function as Full
      Endogenous Agonists at Select Melanocortin Receptors.
AB  - beta-Defensin 3 (BD3) was identified as a ligand for the melanocortin receptors
      (MCRs) in 2007, although the pharmacology activity of BD3 has not been clearly
      elucidated. Herein, it is demonstrated that human BD3 and mouse BD3 are full
      micromolar agonists at the MCRs. Furthermore, mouse beta-defensin 1 (BD1) and
      human BD1 are also MCR micromolar agonists. This work identifies BD1 as an
      endogenous MCR ligand and clarifies the controversial role of BD3 as a micromolar
      agonist.

PMID- 29578345
TI  - A Two-Step Procedure for the Overall Transamidation of 8-Aminoquinoline Amides
      Proceeding via the Intermediate N-Acyl-Boc-Carbamates.
AB  - Herein a two-step strategy for achieving overall transamidation of 8
      aminoquinoline amides has been explored. In this protocol, the 8-aminoquinoline
      amides were first treated with Boc2O and DMAP to form the corresponding N-acyl
      Boc-carbamates, which were found to be sufficiently reactive to undergo
      subsequent aminolysis with different amines in the absence of any additional
      reagents or catalysts. To demonstrate the utility of this approach, it was
      applied on a number of 8-aminoquinoline amides from the recent C-H
      functionalization literature, enabling access to a range of elaborate amide
      derivatives in good to high yields.

PMID- 29578346
TI  - Wide-Range Near-Infrared Sensitizing 1 H-Benzo[ c, d]indol-2-ylidene-Based
      Squaraine Dyes for Dye-Sensitized Solar Cells.
AB  - NIR absorbing squaraine dyes SQ1-SQ7 having 1 H-benzo[ c, d]indol-2-ylidene as a
      donor moiety were designed for application in DSSCs. Annulation of the benzene
      ring to an 3 H-indolium-based anchor moiety led to a red-shifted and broadened
      absorption band on TiO2 film, which were reflected in the improved short-circuit
      current density of SQ2 (6.22 mA cm-2) compared to the nonbenzene fused derivative
      SQ1 (4.39 mA cm-2). Although the introduction of a butoxy (SQ4: 806 nm) or
      dialkylamino group (SQ5-SQ7: 815-820 nm) to the 1 H-benzo[ c, d]indol-2-ylidene
      based donor moiety resulted in red-shifted absorption maxima in ethanol compared
      to the nonsubstituted derivative SQ2 (784 nm), the HOMO energy level of SQ4-SQ7
      gave rise to an undesirable approximation to the redox potential of I-/I3-. Thus,
      the butoxy (SQ4: 0.56) and dialkylamino (SQ5-SQ7: 0.25-0.30) derivatives had
      relatively lower conversion efficiencies. Since the 2-ethylhexyl derivative SQ3
      exhibited red-shifted absorption (lambdamax: 796 nm), suitable HOMO and LUMO
      energy levels, and relatively efficient restriction of charge recombination, this
      dye achieved the highest conversion efficiency (1.31%), along with a high IPCE
      response of over 20% over a wide range from 640 to 860 nm and an onset of IPCE at
      1000 nm.

PMID- 29578348
TI  - Gravitationally Driven Wicking for Enhanced Condensation Heat Transfer.
AB  - Vapor condensation is routinely used as an effective means of transferring heat
      or separating fluids. Filmwise condensation is prevalent in typical industrial
      scale systems, where the condensed fluid forms a thin liquid film due to the high
      surface energy associated with many industrial materials. Conversely, dropwise
      condensation, where the condensate forms discrete liquid droplets which grow,
      coalesce, and shed, results in an improvement in heat transfer performance of an
      order of magnitude compared to filmwise condensation. However, current state-of
      the-art dropwise technology relies on functional hydrophobic coatings, for
      example, long chain fatty acids or polymers, which are often not robust and
      therefore undesirable in industrial conditions. In addition, low surface tension
      fluid condensates, such as hydrocarbons, pose a unique challenge because common
      hydrophobic condenser coatings used to shed water (with a surface tension of 73
      mN/m) often do not repel fluids with lower surface tensions (<25 mN/m). We
      demonstrate a method to enhance condensation heat transfer using gravitationally
      driven flow through a porous metal wick, which takes advantage of the
      condensate's affinity to wet the surface and also eliminates the need for
      condensate-phobic coatings. The condensate-filled wick has a lower thermal
      resistance than the fluid film observed during filmwise condensation, resulting
      in an improved heat transfer coefficient of up to an order of magnitude and
      comparable to that observed during dropwise condensation. The improved heat
      transfer realized by this design presents the opportunity for significant energy
      savings in natural gas processing, thermal management, heating and cooling, and
      power generation.

PMID- 29578349
TI  - Safety of propofol sedation directed by endoscopists: how long should we continue
      to generate evidence?
AB  - The administration of propofol by endoscopists is a source of permanent friction
      with the Societies of Anesthesiology, which is based more on a clear conflict of
      economic interest on the part of the anesthesiologists than supported by
      scientific evidence. Maestro Antolin et al. (1) presented a series of more than
      33,000 sedations performed with propofol by endoscopists, observing a frequency
      of cardiorespiratory adverse events of 0.13%. Rather than confrontation between
      different specialties, where the corporatism of the Anesthesiology Societies and
      their interest in monopolizing the use of a safe drug such as propofol prevails
      with no scientific support, anesthesiologists, endoscopists and nurses should
      instead work together for the benefit of our patients.

PMID- 29578347
TI  - A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle
      Constriction and Inflammation by Targeting GABAA Receptors in the Lung.
AB  - We describe lead compound MIDD0301 for the oral treatment of asthma based on
      previously developed positive allosteric alpha5beta3gamma2 selective GABAA
      receptor (GABAAR) ligands. MIDD0301 relaxed airway smooth muscle at single
      micromolar concentrations as demonstrated with ex vivo guinea pig tracheal rings.
      MIDD0301 also attenuated airway hyperresponsiveness (AHR) in an ovalbumin murine
      model of asthma by oral administration. Reduced numbers of eosinophils and
      macrophages were observed in mouse bronchoalveolar lavage fluid without changing
      mucous metaplasia. Importantly, lung cytokine expression of IL-17A, IL-4, and TNF
      alpha were reduced for MIDD0301-treated mice without changing antiinflammatory
      cytokine IL-10 levels. Automated patch clamp confirmed amplification of GABA
      induced current mediated by alpha1-3,5beta3gamma2 GABAARs in the presence of
      MIDD0301. Pharmacodynamically, transmembrane currents of ex vivo CD4+ T cells
      from asthmatic mice were potentiated by MIDD0301 in the presence of GABA. The
      number of CD4+ T cells observed in the lung of MIDD0301-treated mice were reduced
      by an oral treatment of 20 mg/kg b.i.d. for 5 days. A half-life of almost 14 h
      was demonstrated by pharmacokinetic studies (PK) with no adverse CNS effects when
      treated mice were subjected to sensorimotor studies using the rotarod. PK studies
      also confirmed very low brain distribution. In conclusion, MIDD0301 represents a
      safe and improved oral asthma drug candidate that relaxes airway smooth muscle
      and attenuates inflammation in the lung leading to a reduction of AHR at a dosage
      lower than earlier reported GABAAR ligands.

PMID- 29578351
TI  - Endoscopy and sedation: an inseparable binomial for the gastroenterologist.
AB  - The development of endoscopy and its increasing demand among the population have
      led to a growing need for propofol-based sedation techniques. Benefit is
      indisputable for both patients and endoscopists, but some aspects require
      considering the "who" and "how" of sedation as related to safety and health care
      costs. Propofol is first-choice in endoscopy for the European Society of
      Gastrointestinal Endoscopy because of its fast onset of action and short half
      life, and many reports exist on its safety when used by gastroenterologists
      rather than anesthesiologists. In this issue of REED several originals support
      the efficiency and safety of propofol even for complex, high-risk, or protracted
      procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and
      enteroscopy. Propofol may be safely and effectively administered by a team with
      specific skills acquired through education and using a specific procedure.
      However, difficulties arise in real-world clinical practice that preclude such
      training, which in Spain should be included in the MIR (medico interno residente)
      specialization program curriculum. The Comision Nacional de Digestivo (Spanish
      National Commission on Digestive Diseases), sensitive to this training gap, has
      included in their latest version of the MIR program (under assessment) four
      additional competences, with number 145 (training in deep sedation) being most
      relevant here. In addition, the Spanish Society of Gastrointestinal Endoscopy
      (SEED) has invested significant efforts in sedation training, with over 50
      courses on sedation for endoscopists and nurses. Continuing education and
      training in this field (for instance, refresher courses on advanced
      cardiopulmonary resuscitation) should be a goal for all endoscopy units. Because
      of the diversity found among hospitals, with single or multiple endoscopy rooms,
      efforts should be made to persuade those in charge of gastroenterology and
      anesthesiology departments to establish the necessary care circuits in order to
      guarantee patient safety by developing accurate protocols and promoting consensus
      among the scientific societies involved (Spanish Society for Digestive Diseases
      [SEPD], SEED and Spanish Society of Anaesthesiology, Resuscitation and Pain
      Management [SEDAR]) and their respective national commissions.

PMID- 29578350
TI  - Severe cardiorespiratory complications derived from propofol sedation monitored
      by an endoscopist.
AB  - INTRODUCTION: deep sedation with propofol monitored by an endoscopist in
      different endoscopy units is a controversial subject and the source of conflicts
      of interest between the various scientific societies of Anesthesiology and
      Gastroenterology. Many studies have already demonstrated the efficacy, efficiency
      and low incidence of complications associated with sedation when under the
      control of a trained endoscopist vs an anesthesiologist. MATERIAL AND METHODS:
      the rate of severe cardiorespiratory complications during various endoscopic
      examinations (gastroscopy, colonoscopy, endoscopic retrograde
      cholangiopancreatography [ERCP] and endoscopic ultrasound [EUS]) where sedation
      was controlled by an endoscopist within our unit, from 2011 to 2016, was
      reviewed. RESULTS: during the study period, 33,195 examinations were analyzed.
      The rate of cardiorespiratory complications was 0.13% and the majority were
      severe desaturations. Most cases responded to an opening in the airway associated
      with the interruption of drug infusion and an ambu bag was required in a few
      cases. There were no statistically significant differences between the different
      groups, except for mean age, risk by type of examination and ASA risk, where the
      difference between ERCP and the rest of examinations was statistically
      significant. CONCLUSION: there is a high level of evidence in the scientific
      literature suggesting that sedation controlled by a trained endoscopist is safe,
      effective and efficient. However, further prospective studies are required in
      order to confirm this conclusion due to the fact that the majority of studies to
      date are retrospective.

PMID- 29578352
TI  - Prospective study of the factors associated with poor tolerance to ambulatory
      colonoscopy under conscious sedation.
AB  - BACKGROUND: conscious sedation with benzodiazepines and opiates for colonoscopy
      is a widespread clinical practice. OBJECTIVE: to determine the patient's
      tolerance to colonoscopy and identify the factors associated with lower
      tolerance. METHODS: a prospective, single-center, descriptive study of patients
      undergoing ambulatory colonoscopy under conscious sedation. The pain was assessed
      using a visual analogue scale with a score of 0 to 100 and also qualitatively.
      RESULTS: three hundred patients with a median age of 54 years completed the study
      (p25-75: 45-64); 138 were men (46%). Tolerance was good in 273 cases (91%). The
      median value of tolerance was 13 (p25-p75: 4-33). Pain was considered as mild in
      215 (71.7%), moderate in 57 (19%) and intense in 28 (9.3%). In the univariate
      study, greater pain was associated with females, anxiety, the indication for the
      procedure, the length of time and difficulty of the examination, and the doses of
      sedatives. In the multivariate study, both the indication (OR 2.92, 95% CI = 1.03
      8.2, p < 0.05) and the difficulty of the examination (OR 4.68, 95% CI = 1.6-13.6,
      p < 0.01) were significant. Complications were found in 16 patients (5.3%),
      although all of them were insignificant. CONCLUSIONS: tolerance of patients
      undergoing ambulatory colonoscopy under conscious sedation is good in most cases
      and complications are infrequent and minor. A worse tolerance to the test is
      associated with women patients, individuals with anxiety prior to colonoscopy,
      indication, difficult and longer exploration and lower doses of sedatives.

PMID- 29578353
TI  - Barriers to diabetes awareness and self-help are influenced by people's
      demographics: perspectives of South Asians with type 2 diabetes.
AB  - AIM: To determine whether barriers to diabetes awareness and self-help differ in
      South Asian participants of different demographic characteristics (age, gender,
      and literacy) with type 2 diabetes living in the United Kingdom. METHODS: Six
      focus group discussions (FGDs) were carried out in patients who were categorized
      according to age (30-60 years, >=60 years), gender (male, female) and literacy
      status (literate, illiterate). Data were analysed following the iterative process
      of thematic analysis techniques. RESULTS: Barriers were demographic-specific. The
      illiterate groups reported language as the major barrier to improved diabetes
      awareness and self-help. The literate groups reported that information provided
      by healthcare providers was general, and not specific to their diet/culture.
      Major barriers to adherence to the recommended diet for diabetes included:
      insufficient knowledge/awareness about nutritional content of food (all groups);
      lack of self-will to resist eating sweets, especially during weddings/festivals
      (literate older groups/literate younger females/illiterate older males);
      difficulty cooking separate meals for diabetic and non-diabetic family members
      (illiterate/literate older females). Other barriers to seeking advice/help ranged
      from not wanting to disclose their diabetes as it may affect employment/work
      (literate groups) to fear of being singled out at social gatherings (illiterate
      groups). General lack of motivation to exercise was reported by all groups. Time
      constraints and not knowing what/how to exercise was reported by literate younger
      groups whilst the illiterate older groups reported to not having suitable
      exercising facilities at local communities. Different barriers were also reported
      when accessing healthcare; language barriers (illiterate groups), restricted
      access to doctors' appointments/difficulty attending specific appointment slots
      offered by General Practitioners (literate females). CONCLUSION: Different
      barriers exist to improved awareness about diabetes and self-help in different
      patient demographics. Lack of culturally appropriate diabetes
      educational/awareness programs in the community appeared to be a major barrier in
      most older and illiterate participants while younger participants reported time
      constraint.

PMID- 29578354
TI  - Considerations on accuracy, pattern and possible underlying factors of brain
      microbleed progression in older adults with absence or mild presence of vascular
      pathology.
AB  - Objective To analyse brain microbleed (BMB) progression, its possible underlying
      factors, and the influence of inter-observer differences, in older individuals
      with none or mild vascular pathology. Methods This study analysed magnetic
      resonance images, cognitive, demographic and laboratory data from all individuals
      from the Alzheimer's Disease (AD) Neuroimaging Initiative database who had the
      required sequences for identifying BMBs over three consecutive years at the time
      the database was accessed (January 2016). BMBs were assessed independently by two
      observers with similar levels of experience. Results A total of 291 patients were
      included in the study. The number of individuals with BMBs and the number of BMBs
      per individual slightly and nonsignificantly increased across three consecutive
      years (Y1: 55/291 [19%]; Y2: 61/291 [21%]; Y3: 66/291 [23%]) with 1-2 BMBs and
      (Y1: 11/291 [4%]; Y2: 12/291 [4%]; Y3: 14/291 [5%]) with >= 3 BMBs. Both
      observers identified a similar pattern of BMB prevalence and progression in each
      cognitive group (normal < early/late mild cognitive impairment (MCI) > AD
      patients) despite inter-observer differences (1.5 BMBs, 95% confidence interval 
      3.7, 6.2], kappa=0.543), which were mainly in the cortex. Serum cholesterol was
      the main predictor of change in BMB count between time-points but did not predict
      overall progression. Conclusions Inter-observer differences are always present
      and it is difficult to ascertain their influence in the analysis of BMB
      progression, which was observed in cognitively normal and MCI individuals, but
      not in AD patients. This should be confirmed in further studies.

PMID- 29578355
TI  - Risk factors for hypersensitivity reactions to tocilizumab introduction in
      systemic juvenile idiopathic arthritis.
AB  - OBJECTIVES: The objective of this study is to identify risk factors for
      hypersensitivity reaction (HSR) to tocilizumab (TCZ) in systemic juvenile
      idiopathic arthritis (sJIA). METHODS: Clinical records of 40 patients with sJIA
      administered TCZ at one center were retrospectively reviewed. Patients were
      divided into HSR or non-HSR groups depending on the presence of HSR between the
      first and third TCZ administrations; clinical and laboratory assessments,
      including serum cytokine profile, were compared. RESULTS: Five patients displayed
      HSR following the third TCZ administration. They were significantly younger,
      shorter, and lighter, with a higher peak body temperature than non-HSR patients
      following the third administration. Their serum C-reactive protein (CRP) level
      was undetectable following the first administration but detectable by the third
      administration. Before the third administration, the white blood cell counts and
      serum levels of CRP and sTNFRII were significantly higher in the HSR group than
      in the non-HSR group. The serum levels of interleukin-18 and -6 before the third
      TCZ administration were higher and lower than those before the first
      administration in the HSR and non-HSR groups, respectively. CONCLUSION: Patients
      with sJIA having a younger age, shorter stature, and lighter weight and those
      showing increased disease activity in the early period of TCZ administration may
      be at higher risk of TCZ-induced HSR.

PMID- 29578356
TI  - An unusual case of hematemesis and epistaxis caused by a pheochromocytoma.
AB  - Pheochromocytoma is a rare catecholamine-secreting neoplasm that is the cause of
      hypertension in <0.2% of patients with hypertension. We encountered an unusual
      case of pheochromocytoma involving hematemesis and epistaxis episodes with
      accompanying hypertensive attacks. Venous ectasia was detected in the esophagus.
      Abdominal magnetic resonance imaging revealed an adenoma in the left adrenal
      region. The present case illustrates that pheochromocytoma can mimic different
      clinical conditions.

PMID- 29578357
TI  - African-American caregivers' perspectives on aggressive behaviors in dementia.
AB  - Purpose Although African-American dementia caregivers report less upset and more
      confidence managing aggressive behaviors when compared to whites, their
      contextual experience remains unclear and this study explores that context.
      Methods Semi-structured interviews with 13 African-American family caregivers
      were analyzed using content analysis. Results Two themes emerged, "It's the
      disease...not the person" and "You got to pick your battles." "It's the
      disease...not the person," reframing aggressive behavior, included three sub
      themes. Sometimes the person with dementia seemed like a stranger but caregivers
      remembered "In there somewhere is that person." Aggressive behavior made this
      perspective difficult as they reported, "Sometimes it's hard not to take it
      personal." Premorbid dyadic conflict made caregiving difficult but caregivers
      remembered they were "Not who they were then." "You got to pick your battles,"
      reflecting cognitive and behavioral strategies, also included three sub-themes.
      Participants prioritized caregiving over other commitments by reminding
      themselves "I got to do what I gotta do." Preventing aggressive behaviors was
      most successful when "We didn't argue...we didn't insist" and caregivers
      remembered "Don't put her in a position to fail" when involving the person with
      dementia in activities. Implications African-American caregivers described
      substantial challenges when confronted by aggressive behaviors. Strategies
      employed by caregivers enabled them to maintain a caring perspective and the
      person with dementia to maintain calm. Interventions that help caregivers manage
      aggressive behaviors may benefit by considering the challenges, cultural values,
      and effective strategies used by African-Americans.

PMID- 29578358
TI  - Role of FcalphaR EC2 region in extracellular membrane localization.
AB  - The FcalphaR receptor (CD89) binds to the constant region of Immunoglobulin (Ig)
      A to mediate mucosal immunity [1-2]. FcalphaR consist of five exons: two that
      code for the signal peptide regions S1 & S2, two for the extracellular regions
      EC1 and EC2, and the final exon for the transmembrane/cytoplasmic tail region
      [3]. Previously, we reported that the EC1 region plays an essential role for
      extracellular membrane localization of the receptor [4], where the absence of EC1
      would prevent the variants from localizing to the cell surface, even with a full
      signal peptide. In the case of FcalphaR Variant 4 (lacking the S2 region only),
      there was some "leakiness" to membrane surface localization.

PMID- 29578359
TI  - Approach to oligometastatic disease in head and neck cancer, on behalf of the
      GORTEC.
AB  - Median survival for recurrent/metastatic head and neck squamous cell cancer
      (HNSCC) patients is about 10 months after first-line best systemic treatment. We
      aimed to assess current approaches of oligometastatic HNSCC patients by the
      analysis of current concept and published data (1995-2017) in this population.
      Five-year survival rates are over 20% in selected patients who undergo metastasis
      directed therapy by either surgery or stereotactic irradiation. Human
      papillomavirus(+) HNSCC patients have more disseminated metastases but respond
      more favorably and also benefit from ablative treatments. Treatments of
      oligometastases are expanding rapidly. Unmet needs include revised imaging follow
      up strategies to detect metastases earlier, identification of predictive
      noninvasive biomarkers for treatment guidance, assessment and corrections of
      biases in current studies and randomized clinical trials.

PMID- 29578360
TI  - Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever
      patients complicated with amyloidosis.
AB  - BACKGROUND: Colchicine is the mainstay of the treatment of familial Mediterranean
      fever (FMF). However, 10% of FMF patients do not respond well to colchicine.
      Efficacy of interleukin (IL)-1 inhibitors in reducing attacks have been
      demonstrated in colchicine-resistant FMF (crFMF) patients recently. Colchicine is
      still the only approved drug for the prevention of amyloidosis in FMF and utility
      of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be
      elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in
      patients with crFMF-associated AA amyloidosis in a relatively large single center
      study. METHODS: Medical records of FMF patients complicated with AA amyloidosis
      in our dedicated FMF center were retrospectively reviewed and those patients who
      ever treated with IL-1 inhibitors were enrolled into the study. Patient global,
      physician global assessments (on 0-10 cm visual analog scale), C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and 24-h urinary
      protein excretion values for each visit were recruited from computer-based
      hospital records. Treatment response of patients were assessed with clinical
      symptoms, serum albumin, CRP and ESR values. Renal outcome parameters were
      analyzed on those not receiving renal replacement therapy. RESULTS: Seventeen
      patients were identified with crFMF-amyloidosis that ever treated with IL-1
      inhibitors. Background colchicine therapy was continued in all patients in
      maximal-tolerated dose along with IL-1 inhibitors. All patients benefit from IL-1
      antagonists assessed by patient and physician global assessments. Inflammatory
      markers, CRP and ESR, were significantly reduced in all and normalized in 12 out
      of 17 patients. More importantly, the amount of proteinuria was remarkably
      improved following IL-1 inhibitor therapy (1606 mg/day to 519 mg/day, p = .008).
      Both anakinra and canakinumab were well-tolerated without severe side effects.
      All patients were initially treated with anakinra but switched to canakinumab in
      seven patients (one leukopenia, four injection site reaction, two inefficacy).
      CONCLUSION: We evaluated the clinical and laboratory responses to IL-1 inhibitors
      in crFMF-associated amyloidosis patients. We found significant decreases in CRP,
      ESR and proteinuria after IL-1 inhibitor therapy. This study confirmed that IL-1
      inhibitors are effective for controlling attacks and inflammatory activity in FMF
      patients complicated with AA amyloidosis. Moreover, they reduce or stabilize
      amount of proteinuria and preserve renal function in short-term follow-up.
      Prolonged prospective clinical trials are warranted to assess their long-term
      efficacy in this particular patient group.

PMID- 29578362
TI  - Molecular aspects of hypercholesterolemia treatment: current perspectives and
      hopes.
AB  - Hypercholesterolemia is a pathological condition which has been reported in 39%
      of the worlds' adult population. We aimed to review molecular aspects of current
      and novel therapeutic approaches based on low-density lipoprotein cholesterol
      lowering strategies. Pathogenic mutations in the LDLR, ApoB, PCSK9 and LDLRAP
      genes cause deficient clearance of circulating low-density lipoprotein
      cholesterol particles via hepatic LDL receptor. This leads to increased plasma
      LDL cholesterol levels from birth, which can cause LDL depositions in the
      arterial walls. Ultimately, it progresses to atherosclerosis and an increased
      risk of premature cardiovascular diseases. Currently, statins, Ezetimibe, Bile
      acid sequestrants and PCSK9 inhibitors are the main therapeutic agents for the
      treatment of hypercholesterolemia. Moreover, novel RNA-based therapy had a strong
      impact on therapeutic strategies in recent decades. Additional development in
      understanding of the molecular basis of hypercholesterolemia will provide
      opportunities for the development of targeted therapy in the near future. Key
      Messages The most common genes involved in hypercholesterolemia are LDLR, PCSK9
      and ApoB. Pharmacogenetic effects are typically constrained to pathways closely
      related to the pharmacodynamics and pharmacokinetics. Change in lifestyle and
      diet along with treatment of the underlying disease and drug therapy are the
      current therapeutic strategies.

PMID- 29578361
TI  - Immobilization of Trichoderma harzianum alpha-amylase on PPyAgNp/Fe3O4
      nanocomposite: chemical and physical properties.
AB  - In this study, a new support has been developed by immobilization of alpha
      amylase onto modified magnetic Fe3O4-nanoparticles. The characterization of
      soluble and immobilized alpha-amylases with regards to kinetic parameters, pH,
      thermal stability and reusability was studied. The effect of polypyrrole/silver
      nanocomposite (PPyAgNp) percentage on weight of Fe3O4 and pH on the
      immobilization of alpha-amylase was studied. The highest immobilization
      efficiency (75%) was detected at 10% PPyAgNp/Fe3O4-nanocomposite and pH 7.0.
      Immobilization of alpha-amylase on PPyAgNp/Fe3O4-nanocomposite was characterized
      by FT-IR spectroscopy and scanning electron microscopy. The reusability of the
      immobilized enzyme activity was 80% of its initial activity after 10 reuses. The
      immobilized enzyme was more stable towards pH, temperature and metal ions
      compared with soluble enzyme. The kinetic study appeared higher affinity of
      immobilized enzyme (Km 2.5 mg starch) compared with soluble enzyme (Km 3.5 mg
      starch). In conclusion, the immobilization of alpha-amylase on PPyAgNp/Fe3O4
      nanocomposite could successfully be used in industrial and medical applications.

PMID- 29578363
TI  - High prevalence of serum folate receptor autoantibodies in children with autism
      spectrum disorders.
AB  - BACKGROUND: Supplementation of folic acid by pregnant mothers is thought to lower
      the risk of autism spectrum disorders (ASDs) in the offspring. Folic acid is
      taken up by cells via receptors with high affinity for folate and reduced folic
      acid derivatives. However, this is blocked by the presence of folate receptor
      autoantibodies (FRAA). Cerebral FRAA have been detected with high frequency in
      children with ASDs, suggesting the existence of a link between folic acid uptake
      and disease aetiology. METHODS: We investigated the frequency of FRAA in serum
      samples from 40 children with ASDs and 42 gender- and age-matched children with
      typical development (TD). Serum FRAA concentrations were measured by enzyme
      linked immunosorbent assay. RESULTS: We found a significant difference in the
      frequency of serum FRAA in the two study cohorts. Serum FRAA were present in
      77.5% (31/40) of children with ASDs compared with 54.8% (23/42) of TD children (p
      = 0.03746, Fischer's exact test). Thus, serum FRAA are more prevalent in children
      with ASDs than in TD children. CONCLUSIONS: Our data suggest that children with
      ASDs may have defects in folic acid absorption that play a role in the onset of
      ASDs.

PMID- 29578366
TI  - Trimethylamine N-oxide and ACE inhibitors: fighting a new enemy with an
      established weapon?

PMID- 29578364
TI  - Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90
      transarterial radioembolization versus sorafenib.
AB  - AIM: The aim was to evaluate cost-effectiveness of yttrium-90 transarterial
      radioembolization (TARE) in comparison to sorafenib treatment. PATIENTS &
      METHODS: A single-center, retrospective, observational study was performed, 166
      patients with intermediate-/advanced-stage hepatocellular carcinoma were treated
      with sorafenib and 19 with TARE. The patients out of the sorafenib group matching
      the inclusion criteria for TARE, were reassigned to a subgroup SOR3. RESULTS:
      Mean costs for SOR3 patients amounted to ?27,992 per patient, instead for TARE
      treatment, mean expense per patient was ?17,761 (p = 0.028). Overall survival was
      similar between the two groups, while midterm survival rates (p = 0.012) were
      significantly higher with TARE treatment. CONCLUSION: TARE causes significantly
      lower treatment costs than sorafenib with better outcome in midterm survival.

PMID- 29578365
TI  - The Capicua tumor suppressor: a gatekeeper of Ras signaling in development and
      cancer.
AB  - The transcriptional repressor Capicua (CIC) has emerged as an important rheostat
      of cell growth regulated by RAS/MAPK signaling. Cic was originally discovered in
      Drosophila, where it was shown to be inactivated by MAPK signaling downstream of
      the RTKs Torso and EGFR, which results in signal-dependent responses that are
      required for normal cell fate specification, proliferation and survival of
      developing and adult tissues. CIC is highly conserved in mammals, where it is
      also negatively regulated by MAPK signaling. Here, we review the roles of CIC
      during mammalian development, tissue homeostasis, tumor formation and therapy
      resistance. Available data indicate that CIC is involved in multiple biological
      processes, including lung development, liver homeostasis, autoimmunity and
      neurobehavioral processes. Moreover, CIC has been shown to be involved in tumor
      development as a tumor suppressor, both in human as well as in mouse models.
      Finally, several lines of evidence implicate CIC as a determinant of sensitivity
      to EGFR and MAPK pathway inhibitors, suggesting that CIC may play a broader role
      in human cancer than originally anticipated.

PMID- 29578367
TI  - Incidence and survival in sinonasal carcinoma: a Danish population-based,
      nationwide study from 1980 to 2014.
AB  - BACKGROUND: Sinonasal cancers are rare and comprise <1% of all malignancies. This
      study describes incidence and survival in sinonasal carcinomas in Denmark from
      1980 to 2014. METHODS: All patients registered in the Danish Cancer Registry in
      the period were included. Age-adjusted incidence rate, average annual percentage
      change, and relative survival were calculated. Age-period-cohort models were
      constructed. RESULTS: 1,720 patients with sinonasal carcinoma (median age 67
      years, 63% males) were identified. There was no significant change in age
      adjusted incidence; 0.70 in 1980 to 0.43 per 100,000 in 2014 (p > .05). Relative
      5- and 10-year survival were 52% and 40% for men, 58% and 42% for women. An
      increase in 5-year survival from 1980 to 2014 from 46% to 65% (p < .05) was
      found. Nasal carcinomas had a significantly better relative survival compared to
      sinus carcinoma, as did squamous cell carcinomas when compared to neuroendocrine
      malignancies. CONCLUSION: In Denmark between 1980 and 2014, the incidence of
      sinonasal carcinomas has been stable and the relative survival has increased
      significantly.

PMID- 29578368
TI  - Protective effects of banana pectin against aluminum-induced cognitive impairment
      and aluminum accumulation in mice.
AB  - To investigate the effect of pectin on absorption and bio-toxicity of aluminum,
      pectin extract (100 mg kg-1 d-1) from banana pulp was orally administrated to
      aluminum exposed mice (35 mg kg-1 d-1) for 6 weeks. Our result showed that body
      weight gain of the mice treated with aluminum plus banana pectin was 32.5% higher
      than that of mice exposed to aluminum alone after 6 weeks of the administration.
      In both the step-down inhibitory avoidance task and Morris water maze test,
      memory retention of aluminum-exposed mice was significantly improved by the
      pectin administration. Treatment with banana pectin effectively prevented
      absorption of aluminum from the gastrointestinal tract, total aluminum excretion
      of mice treated with banana pectin plus aluminum was 9.3% higher than that of
      mice exposed to aluminum alone on the 12th day. Aluminum level in serum,
      cerebrum, or cerebellum of mice treated with aluminum plus banana pectin was
      30.8%, 17.5%, or 17.9% lower than that of mice exposed to aluminum alone on the
      42nd day, respectively. In conclusion, banana pectin extract can effectively
      reduce aluminum toxicity in mice.

PMID- 29578369
TI  - Migration of metal clips into the duodenum after laparoscopic cholecystectomy: A
      report of two cases.
AB  - Migration of metal clips into the duodenum after laparoscopic cholecystectomy is
      rare. We herein present two cases of migration of metal clips into the duodenum
      in patients who developed upper quadrant discomfort and a poor appetite after
      laparoscopic cholecystectomy. Gastroscopy revealed metal clips in the duodenum.
      In one patient, the clip dropped from the duodenum after 2 months; the other
      patient went to another institution to undergo duodenotomy. The mechanism
      underlying migration of a metal clip into the duodenum remains unclear but might
      be related to chronic inflammation and duodenal peristalsis. In conclusion,
      clinicians must remember that metal clips can migrate after laparoscopic
      cholecystectomy and later cause complications.

PMID- 29578371
TI  - Extra View: Sirt1 Acts As A Gatekeeper Of Replication Initiation To Preserve
      Genomic Stability.
AB  - Since the discovery of a yeast gene silencing modifier (Silent Information
      Modifier 2, SIR2) and its role in maintaining genomic stability more than two
      decades ago, SIR2 homologs (sirtuins) were identified in diverse species.
      Sirtuins are protein deacetylases that play diverse roles in proper cellular
      metabolism including cell cycle progression and maintenance of genomic stability.
      In yeast, SIR2 interacts with replication origins and protein complexes that
      affect both replication origin usage and gene silencing. In metazoans, the
      largest SIR2 homolog, SIRT1, is implicated in epigenetic modifications, circadian
      signaling, DNA recombination and DNA repair. Until recently, very few studies
      investigated the role of mammalian SIRT1 in modulating DNA replication. We
      discuss a newly characterized interaction between human SIRT1 and the DNA
      replication machinery, reviewing data from recent studies that have investigated
      how complex signaling pathways that involve SIRT1 affect cellular growth
      regulatory circuits.

PMID- 29578373
TI  - Application of mindfulness-based stress reduction to a stress management
      intervention in a study of a mining sector company.
AB  - PURPOSE: The aim of this article was to check whether mindfulness-based stress
      reduction (MBSR) is an effective intervention in reducing work-related stress in
      the case of workers in a copper mine. METHODS: Sixty six employees were
      randomized to the experimental group (32 participants) or to the control group
      (34 participants). Work-related stress was measured using the job content
      questionnaire (JCQ) and mental health was measured using the general health
      questionnaire (GHQ-28) Experimental manipulation was 40-h MBSR training. RESULTS:
      Multivariate repeated-measures analysis of variance revealed a significant
      increase of JCQ decision latitude (F = 17.36, p < 0.001) and social support
      (supervisor F = 9.00, p < 0.004; coworker F = 5.61, p < 0.020), and a significant
      decrease in GHQ-28 anxiety (F = 5.28, p < 0.079) and depression (F = 3.95, p <
      0.048) due to the intervention. CONCLUSIONS: The study confirms that MBSR can be
      effective in reducing stress resulting from the external risk (and/or imagined
      fear) of losing one's health or life. The use of MBSR could be recommended in
      health and safety activities in difficult and dangerous work conditions, such as
      mining, to promote workers' well-being.

PMID- 29578370
TI  - Lipodystrophic syndromes due to LMNA mutations: recent developments on
      biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives.
AB  - Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies
      including muscular dystrophies, lipodystrophies, and premature ageing syndromes.
      LMNA mutations have been shown to alter nuclear structure and stiffness, binding
      to partners at the nuclear envelope or within the nucleoplasm, gene expression
      and/or prelamin A maturation. LMNA-associated lipodystrophic features, combining
      generalized or partial fat atrophy and metabolic alterations associated with
      insulin resistance, could result from altered adipocyte differentiation or from
      altered fat structure. Recent studies shed some light on how pathogenic A-type
      lamin variants could trigger lipodystrophy, metabolic complications, and
      precocious cardiovascular events. Alterations in adipose tissue extracellular
      matrix and TGF-beta signaling could initiate metabolic inflexibility. Premature
      senescence of vascular cells could contribute to cardiovascular complications. In
      affected families, metabolic alterations occur at an earlier age across
      generations, which could result from epigenetic deregulation induced by LMNA
      mutations. Novel cellular models recapitulating adipogenic developmental pathways
      provide scalable tools for disease modeling and therapeutic screening.

PMID- 29578372
TI  - Optimization of mRNA untranslated regions for improved expression of therapeutic
      mRNA.
AB  - mRNA based therapies hold great promise for the treatment of genetic diseases.
      However, this therapeutic approach suffers from multiple challenges including the
      short half-life of exogenously administered mRNA and subsequent protein
      production. Modulation of untranslated regions (UTR) represents one approach to
      enhance both mRNA stability and translation efficiency. The current studies
      describe and validate screening methods using a diverse set of 5'UTR and 3'UTR
      combinations for improved expression of the Arginase 1 (ARG1) protein, a
      potential therapeutic mRNA target. Data revealed a number of critical aspects
      which need to be considered when developing a screening approach for engineering
      mRNA improvements. First, plasmid-based screening methods do not correlate with
      protein expression driven by exogenously expressed mRNA. Second, improved ARG1
      protein production was driven by increased translation and not improved mRNA
      stability. Finally, the 5' UTR appears to be the key driver in protein expression
      for exogenously delivered mRNA. From the testing of the combinatorial library,
      the 5'UTR for complement factor 3 (C3) and cytochrome p4502E1 (CYP2E1) showed the
      largest and most consistent increase in protein expression relative to a
      reference UTR. Collectively, these data provide important information for the
      development and optimization of therapeutic mRNAs.

PMID- 29578374
TI  - Dancing Effects on Preschoolers' Sensorimotor Synchronization, Balance, and
      Movement Reaction Time.
AB  - In the present study, we compared an experimental group of preschool children ( n
      = 22; mean age = 5 years, 8 months) who followed an 8-week dance program with a
      control group ( n = 20; mean age = 5 years, 5 months) on pre-post measures of
      sensorimotor synchronization (K-Rhythm Test), balancing on one leg and movement
      reaction time. Compared with the control participants, the dance group
      demonstrated significantly better pretest to posttest improvements on
      sensorimotor synchronization and balance (but not movement reaction time).
      Considering the importance of sensorimotor synchronization and balance for
      subsequent child development and performance of daily and sport activities, these
      results suggest that dancing should be included in early childhood curricula.

PMID- 29578375
TI  - A kinematic comparison between long-line and cross-court top spin forehand in
      competitive table tennis players.
AB  - The aim of the present study was to compare the biomechanical characteristics of
      the table tennis top spin shot when played cross-court (CC) or long-line (LL) in
      competitive table tennis players. Seven national level players respectively
      completed 10 long-line and 10 cross-court top spin shots responding to a standard
      ball machine. A stereophotogrammetric system was used to track body segments
      while executing the motion. Significantly more flexed right knee and elbow angles
      were measured at the moment of maximum velocity of the racket (MMV) in LL. In
      addition, significantly greater angles between the feet and the table and between
      the shoulders and the table at the MMV, indicated more pronounced rotation angles
      of the lower upper and upper-body in LL compared to CC with respect to the table.
      A higher inclination of the racket at the MMV was found in LL. The elbow flexion
      and the racket inclination may be associated to the direction of the shot. The
      present findings show that kinematic differences exist between the LL and the CC
      topspin forehand in competitive table tennis players. Coaches should be aware of
      these differences to adopt the optimal teaching strategies and to reproduce
      proper joint angles during training.

PMID- 29578376
TI  - From 'automation' to 'autonomy': the importance of trust repair in human-machine
      interaction.
AB  - Modern interactions with technology are increasingly moving away from simple
      human use of computers as tools to the establishment of human relationships with
      autonomous entities that carry out actions on our behalf. In a recent commentary,
      Peter Hancock issued a stark warning to the field of human factors that attention
      must be focused on the appropriate design of a new class of technology: highly
      autonomous systems. In this article, we heed the warning and propose a human
      centred approach directly aimed at ensuring that future human-autonomy
      interactions remain focused on the user's needs and preferences. By adapting
      literature from industrial psychology, we propose a framework to infuse a unique
      human-like ability, building and actively repairing trust, into autonomous
      systems. We conclude by proposing a model to guide the design of future autonomy
      and a research agenda to explore current challenges in repairing trust between
      humans and autonomous systems. Practitioner Summary: This paper is a call to
      practitioners to re-cast our connection to technology as akin to a relationship
      between two humans rather than between a human and their tools. To that end,
      designing autonomy with trust repair abilities will ensure future technology
      maintains and repairs relationships with their human partners.

PMID- 29578377
TI  - Statement of Retraction.

PMID- 29578378
TI  - Preparation of high affinity antibody for ribavirin with new haptens and residue
      analysis in chicken muscle, eggs and duck muscle.
AB  - In this work, high affinity polyclonal antibodies for ribavirin (RBV) from new
      haptens were prepared and were used to analyse RBV residues in chicken muscle,
      eggs and duck muscle. The new haptens were synthesised with different spacers,
      and the best antibody was obtained with an IC50 value as low as 0.61 ng/mL in
      indirect competitive enzyme-linked immunosorbent assay (ELISA). The cross
      reactivities with another five antiviral drugs including amantadine, rimantadine,
      moroxydine, zanamivir and oseltamivir were less than 0.1%, which indicated the
      good specificity of the antibody. An ELISA was developed based on the antibody
      and applied to detect RBV in multi-food matrices. The sample preparation prior to
      detection only needed simple dilution after trichloroacetic acid extraction. The
      limits of detection were 1.07, 1.18 and 1.03 MUg/kg in chicken muscle, eggs and
      duck muscle, respectively. Recoveries ranged from 89.0% to 112.7% with
      coefficients of variation below 13.0%. Ten blind samples of chicken muscle were
      analysed simultaneously by ELISA and liquid chromatography-tandem mass
      spectrometry, and a good correlation between the methods was observed. The
      results indicated that the high affinity antibody could be applied for the simple
      and fast detection of RBV in multi-food matrices.

PMID- 29578379
TI  - The relationship between strength asymmetries and jumping performance in
      professional volleyball players.
AB  - Knee peak torque (PT) is associated to jump performance in volleyball players. It
      is not clear whether muscle strength imbalances of the knee joint can influence
      jump performance. The purpose of study was to analyse the association between PT
      and knee muscular imbalances with jump performance in professional volleyball
      players. Eleven elite male volleyball players (90.3 +/- 9.7 kg body mass and 1.94
      +/- 0.06 m height) were evaluated in an isokinetic dynamometer at speeds of 60,
      180 and 300 deg/s. Muscle strength imbalances were obtained through calculation
      of contralateral deficit between limbs and the conventional ratio
      (hamstrings/quadriceps). Countermovement jump (CMJ) was performed on a force
      plate to calculate mechanical power and height. Association was found between
      knee extensor PT at 180 deg/s with CMJ power (r = 0.610, p = 0.046). Conventional
      ratio at 300 deg/s showed negative association with CMJ (r = -0.656, p = 0.029).
      The optimal ratio between knee extensors PT in relation to the flexors PT is
      associated with the greater mechanical power in CMJ. Contralateral deficit does
      not seem to be associated with the CMJ performance. Considering the knee extensor
      PT is associated with CMJ power, our findings suggest that strength-based
      training in volleyball athletes should not omit the conventional muscle ratio.

PMID- 29578380
TI  - Time-motion analysis of goalball players in attacks: differences of the player
      positions and the throwing techniques.
AB  - In this study, we aimed to analyse goalball players time-motion variables
      (distance covered, time spent, maximum and average velocities) in official
      goalball match attacks, taking into account the attack phases (preparation and
      throwing), player position (centres and wings) and throwing techniques (frontal,
      spin and between the legs). A total of 365 attacks were assessed using a video
      based method (2D) through manual tracking using the Dvideo system. Inferential
      non-parametric statistics were applied for comparison of preparation vs. throwing
      phase, wings vs. centres and, among the throwing techniques, frontal, spin and
      between the legs. Significant differences were found between the attack
      preparation versus the throwing phase for all player time-motion variables:
      distance covered, time spent, maximum player velocity and average player
      velocity. Wing players performed most of the throws (85%) and covered longer
      distances than centres (1.65 vs 0.31 m). The between the legs and the spin
      throwing techniques presented greater values for most of the time-motion
      variables (distance covered, time spent and maximum player velocity) than did the
      frontal technique in both attack phases. These findings provide important
      information regarding players' movement patterns during goalball matches that can
      be used to plan more effective training.

PMID- 29578381
TI  - Stride length: the impact on propulsion and bracing ground reaction force in
      overhand throwing.
AB  - Propulsion and bracing ground reaction force (GRF) in overhand throwing are
      integral in propagating joint reaction kinetics and ball velocity, yet how stride
      length effects drive (hind) and stride (lead) leg GRF profiles remain unknown.
      Using a randomised crossover design, 19 pitchers (15 collegiate and 4 high
      school) were assigned to throw 2 simulated 80-pitch games at +/-25% of their
      desired stride length. An integrated motion capture system with two force plates
      and radar gun tracked each throw. Vertical and anterior-posterior GRF was
      normalised then impulse was derived. Paired t-tests identified whether
      differences between conditions were significant. Late in single leg support, peak
      propulsion GRF was statistically greater for the drive leg with increased stride.
      Stride leg peak vertical GRF in braking occurred before acceleration with longer
      strides, but near ball release with shorter strides. Greater posterior shear GRF
      involving both legs demonstrated increased braking with longer strides.
      Conversely, decreased drive leg propulsion reduced both legs' braking effects
      with shorter strides. Results suggest an interconnection between normalised
      stride length and GRF application in propulsion and bracing. This work has shown
      stride length to be an important kinematic factor affecting the magnitude and
      timing of external forces acting upon the body.

PMID- 29578382
TI  - Pre-operative screening for asymptomatic bacteriuria and associations with post
      operative outcomes in patients with spinal cord injury.
AB  - CONTEXT: Screening for asymptomatic bacteriuria (ASB) before non-urologic surgery
      is common but of unclear benefit. Our aim was to describe pre-operative ASB
      screening and post-operative outcomes in patients with neurogenic bladder due to
      spinal cord injury (SCI). METHODS: This was a descriptive retrospective cohort
      study of adults with SCI undergoing neurosurgical spine or orthopedic lower limb
      surgery from 10/1/2012-9/30/2014 at Veterans Affairs (VA) medical centers.
      National VA datasets and medical record review was used to describe frequency of
      pre-operative ASB screening, presence of ASB, and association with post-operative
      surgical site infection, urinary tract infection, and hospital readmission.
      RESULTS: 175 patients were included. Although over half of patients had pre
      operative ASB screening, only 30.8% actually had pre-operative ASB. 15.2% of
      patients screened were treated for ASB with antibiotics before surgery. Post
      operative urinary tract infection (UTI) or surgical site infection (SSI) occurred
      in 10 (5.7%) patients, and 20 patients (11.4%) were readmitted within 30 days.
      Neither ASB screening nor the presence of pre-operative ASB were associated with
      these post-op outcomes (p > 0.2 for all). CONCLUSION: Pre-operative ASB screening
      is common in patients with SCI undergoing elective spine and lower limb surgery,
      although ASB occurs in less than 1/3rd of cases. There were no associations
      between pre-operative ASB and outcomes. Further studies evaluating the clinical
      benefit of this practice in patients with SCI should be performed.

PMID- 29578383
TI  - Prevalence and associated factors of domestic violence among pregnant women
      attending routine antenatal care in Nepal.
AB  - AIMS: The primary aim of this study was to assess the prevalence of domestic
      violence (DV) and its associated factors among pregnant women in Nepal. The
      secondary aims were to investigate disclosure of DV by women to health-care
      personnel and to assess whether health-care personnel had asked women about their
      experience of DV. METHODS: This cross-sectional study included 2004 pregnant
      women between 12 and 28 weeks of gestation attending routine antenatal care at
      two hospitals in Nepal from August 2014 to November 2015. In this study, DV was
      defined as fear of a family member and/or an experience of physical, emotional or
      sexual violence. Associated risk factors were analysed using logistic regression
      analyses. RESULTS: Twenty-one per cent of the women had experienced DV; 12.5%
      experienced fear only, 3.6% violence only and 4.9% experienced both violence and
      fear. Less than 2% per cent reported physical violence during pregnancy. This
      study found that just 17.7% had ever been asked by health-care personnel about
      DV, and of the women who had reported DV, only 9.5% had disclosed their
      experience to health-care personnel. Women of young age and low socio-economic
      status were more likely to have experienced DV. Women who reported having their
      own income and the autonomy to use it were at significantly lower risk of DV
      compared to women with no income. CONCLUSIONS: A substantial proportion of women
      reported having experienced DV. Victims had rarely disclosed their experience of
      DV to health-care personnel. This study underlines the importance of integrating
      systematic assessment of DV in antenatal care.

PMID- 29578384
TI  - Start and turn performances of elite sprinters at the 2016 European Championships
      in swimming.
AB  - The aim of this study was to examine the performance characteristics of male and
      female finalists in the 100-m distance at the 2016 European Championships in
      swimming (long-course-metre). The performances of all 64 (32-males and 32
      females) were analysed (8 swimmers per event; Freestyle, Backstroke, Breaststroke
      and Butterfly). A set of start and turn parameters were analysed. In the start
      main outcome, male swimmers were faster in Butterfly (5.71 +/- 0.14s) and females
      in Freestyle (6.68 +/- 0.28s). In the turn main outcome, male and female swimmers
      were faster in Freestyle (males: 9.55 +/- 0.13s; females: 10.78 +/- 0.28s). A
      significant and strong stroke effect was noted in the start and turn main
      outcome, in both sexes. In the start plus the turn combined, males and females
      were faster in Freestyle (males: 15.40 +/- 0.20s; females: 17.45 +/- 0.54s). The
      start and the turn combined accounted almost one-third of the total race time in
      all events, and non-significant differences (p > 0.05) were noted across the four
      swim strokes. Once this research made evident the high relevance of start and
      turns, it is suggested that coaches and swimmers should dedicate an expressive
      portion of the training perfecting these actions.

PMID- 29578385
TI  - Comparison of step-by-step kinematics of resisted, assisted and unloaded 20-m
      sprint runs.
AB  - This investigation examined step-by-step kinematics of sprint running
      acceleration. Using a randomised counterbalanced approach, 37 female team
      handball players (age 17.8 +/- 1.6 years, body mass 69.6 +/- 9.1 kg, height 1.74
      +/- 0.06 m) performed resisted, assisted and unloaded 20-m sprints within a
      single session. 20-m sprint times and step velocity, as well as step length, step
      frequency, contact and flight times of each step were evaluated for each
      condition with a laser gun and an infrared mat. Almost all measured parameters
      were altered for each step under the resisted and assisted sprint conditions
      (eta2 >= 0.28). The exception was step frequency, which did not differ between
      assisted and normal sprints. Contact time, flight time and step frequency at
      almost each step were different between 'fast' vs. 'slow' sub-groups (eta2 >=
      0.22). Nevertheless overall both groups responded similarly to the respective
      sprint conditions. No significant differences in step length were observed
      between groups for the respective condition. It is possible that continued
      exposure to assisted sprinting might allow the female team-sports players studied
      to adapt their coordination to the 'over-speed' condition and increase step
      frequency. It is notable that step-by-step kinematics in these sprints were easy
      to obtain using relatively inexpensive equipment with possibilities of direct
      feedback.

PMID- 29578386
TI  - The influence of spatial distribution on add-on therapy of designed Ca-Alg/CS
      MEMs system.
AB  - To improve the efficacy and reduce the systemic toxicity of the diabetes
      mellitus, herewith, we developed a novel microparticles-embedded microcapsules
      (MEMs) system, synthesized from calcium alginate/chitosan (Ca-Alg/CS), by
      emulsion gelation using a high voltage electrostatic droplet generator. In our
      study, we selected two antidiabetic drugs insulin (INS) and metformin (MET) as
      model drugs to investigate different spatial distribution appropriate of MEMs
      system. Characterization based on particle size and morphology, encapsulation
      efficiency and drug loading, as well as drug delivery properties were carried out
      on the MEMs system. Typical multi-chamber structure was shown by SEM and the
      optical spectra. The average diameters of microparticles and Ca-Alg/CS MEMs were
      2100 nm and 410 MUm, respectively. Insulin and MET were embedded into MEMs via
      electrostatic reaction according to FT-IR spectra. Moreover, drug loading and
      encapsulation efficiency of INS were higher than that of MET in this system when
      drugs were loaded alone or together. More importantly, this system has potential
      for orderly drug release and well sustained release when MET in the inner and INS
      in the outer space could be applied as a combination therapy for diabetes. The
      obtained in vivo experimental data on diabetes rats has shown that the designed
      MEMs system resulted in a higher hypoglycemic effect within add-on therapy.

PMID- 29578391
TI  - Editorial: The Biologic Era: A Comprehensive Approach for Inflammatory and Immune
      mediated Diseases.

PMID- 29578387
TI  - Identifying natural compounds as multi-target-directed ligands against
      Alzheimer's disease: an in silico approach.
AB  - Alzheimer's disease (AD) is a multi-factorial disease, which can be simply
      outlined as an irreversible and progressive neurodegenerative disorder with an
      unclear root cause. It is a major cause of dementia in old aged people. In the
      present study, utilizing the structural and biological activity information of
      ligands for five important and mostly studied vital targets (i.e. cyclin
      dependant kinase 5, beta-secretase, monoamine oxidase B, glycogen synthase kinase
      3beta, acetylcholinesterase) that are believed to be effective against AD, we
      have developed five classification models using linear discriminant analysis
      (LDA) technique. Considering the importance of data curation, we have given more
      attention towards the chemical and biological data curation, which is a difficult
      task especially in case of big data-sets. Thus, to ease the curation process we
      have designed Konstanz Information Miner (KNIME) workflows, which are made
      available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were
      appropriately validated based on the predictions for experiment derived data from
      test sets, as well as true external set compounds including known multi-target
      compounds. The domain of applicability for each classification model was checked
      based on a confidence estimation approach. Further, these validated models were
      employed for screening of natural compounds collected from the InterBioScreen
      natural database ( https://www.ibscreen.com/natural-compounds ). Further, the
      natural compounds that were categorized as 'actives' in at least two
      classification models out of five developed models were considered as multi
      target leads, and these compounds were further screened using the drug-like
      filter, molecular docking technique and then thoroughly analyzed using molecular
      dynamics studies. Finally, the most potential multi-target natural compounds
      against AD are suggested.

PMID- 29578392
TI  - Editorial: Pharmacological Therapy to Prevent Sudden Cardiac Death: Indications
      and Limitations in the Era of Devices.

PMID- 29578393
TI  - Prevalence and predictors of tricyclic antidepressant use among elderly Koreans
      in primary-care and specialty clinics.
AB  - OBJECTIVES: Tricyclic antidepressants (TCAs) are prescribed with caution in the
      elderly due to diverse side effects. We analyzed the patterns of TCA use in
      elderly patients in primary-care and specialty clinics and investigated factors
      influencing TCA prescriptions. MATERIALS AND METHODS: Elderly patients (>= 65
      years old) prescribed antidepressants in primary-care clinics in 2013 were
      included from the Health Insurance Review and Assessment Service-Aged Patient
      Sample (HIRA-APS). Prevalence of TCA prescriptions was assessed by insurance
      coverage status, clinical specialty, and region. Multiple logistic regression
      analysis was performed to compute odds ratios (ORs) and 95% confidence intervals
      (CIs) for factors associated with TCA prescriptions. RESULTS: TCAs and selective
      serotonin reuptake inhibitors (SSRIs) comprised 45.2% and 15.0% of all
      antidepressant prescriptions, respectively. TCAs comprised 61.5% and 20.7% of
      antidepressant prescriptions for pain and depression, respectively. Patients aged
      >= 85 years were less likely to be treated with TCAs (OR 0.81, 95% CI 0.79 -
      0.84) than those aged 65 - 69 years. The odds for being prescribed TCAs were
      higher for patients residing in cities (OR 1.20, 95% CI 1.18 - 1.23), treated in
      nonpsychiatric clinics (OR 5.64, 95% CI 5.53 - 5.76), and those covered by
      Veteran's Health (OR 1.62, 95% CI 1.37 - 1.90) when compared to patients residing
      in the Seoul metropolitan area, treated in psychiatric clinics, or covered by
      National Health Insurance, respectively. The prescriptions of TCAs with pain
      diagnoses were much higher than prescriptions for depression (OR 1.87, 95% CI
      1.82 - 1.93). CONCLUSIONS: Compared with a 2005 report, the prevalence of TCA
      prescriptions in elderly patients in Korea has decreased substantially, but
      remains high. Various efforts should be considered to reduce TCA prescriptions in
      the elderly.?.

PMID- 29578394
TI  - Comparative efficacy and safety of TNF-inhibitor plus methotrexate versus oral
      triple therapy in patients with active rheumatoid arthritis inadequately
      responding to methotrexate: A meta-analysis of randomized controlled trials.
AB  - AIMS: The study aimed to assess the efficacy and safety of tumor necrosis factor
      inhibitor (TNFI) with methotrexate (MTX) vs. oral triple therapy in patients with
      active rheumatoid arthritis (RA), showing inadequate response to MTX. MATERIALS
      AND METHODS: We performed a meta-analysis of three randomized controlled trials
      (RCTs) (913 MTX-resistant RA patients) to examine the relative efficacy and
      safety of TNFI+MTX compared to triple therapy (hydroxychloroquine, sulfasalazine,
      MTX) in patients with RA responding inadequately to MTX. RESULTS: The American
      College of Rheumatology's 70% improvement (ACR70) response rate was significantly
      higher for TNFI+MTX-treated patients than for triple therapy-treated controls (RR
      1.549, 95% confidence interval (CI) 1.087 - 2.207, p = 0.016). However, the ACR20
      and ACR50 response rates did not differ between the TNFI+MTX group and the triple
      therapy group. The total Sharp score was significantly lower in TNFI+MTX-treated
      patients than in triple therapy-treated controls (SMD -0.173, 95% CI -0.301 to 
      0.045, p = 0.008). There was no significant difference related to the number of
      patients with serious adverse events between the TNFI+MTX group and the triple
      therapy group (RR 1.033, 95% CI 0.710 - 1.504, p = 0.864); however, TNFI+MTX
      resulted in higher infection rates than triple therapy (RR 1.513, 95% CI 1.149 -
      1.992, p = 0.004). CONCLUSION: TNFI+MTX was found to be more effective than
      triple therapy in active RA patients inadequately responsive to MTX, but it is
      associated with a higher risk of infection.?.

PMID- 29578395
TI  - The Dejerine Foundation.

PMID- 29578396
TI  - Nephritis-associated plasmin receptor (NAPlr) positive glomerulonephritis caused
      by Aggregatibacter actinomycetemcomitans bacteremia: A case report.
AB  - Infection-related glomerulonephritis (IRGN) develops after various infections. It
      was previously thought to be caused by Streptococcus species alone but can also
      be caused by other pathogens. Nephritis-associated plasmin receptor (NAPlr) was
      discovered as a candidate nephritis-inducing factor in acute post-streptococcal
      glomerulonephritis. More recently, renal lesions caused by other pathogens were
      found to be positive for the same molecular marker. We report the case of a 64
      year-old man who experienced repeated fever for several months and presented with
      progressively-deteriorating renal function. He had previously undergone aortic
      valve replacement. Aggregatibacter actinomycetemcomitans, a component of the oral
      flora, was detected in a blood culture. Renal biopsy showed diffuse proliferative
      glomerulonephritis. Immunofluorescence staining of the kidney specimen was
      positive for immunoglobulins, complements, and NAPlr. The patient was diagnosed
      with infectious endocarditis and IRGN. Six weeks of intravenous antibiotic
      therapy improved the patient's clinical condition and kidney function. In this
      case, IRGN was caused by a rare pathogen. This is the first published case to
      show NAPlr positivity in the glomeruli after systemic infection with the
      periodontal bacteria, Aggregatibacter actinomycetemcomitans. This case and
      subsequent research might expand the concept of IRGN, anchored by NAPlr as a key
      diagnostic biomarker.?.

PMID- 29578397
TI  - Fibrillary glomerulonephritis in an HIV patient without concurrent hepatitis C
      infection: Case report and review of the literature?.
AB  - The most common renal disease associated with human immunodeficiency virus
      infection (HIV) is HIV-associated nephropathy (HIVAN), especially in the African
      American patient population. However, various patterns of glomerulonephritis (GN)
      are not uncommon, collectively accounting for nearly half of the renal biopsies
      performed in HIV patients. Most GNs that occur in HIV patients are immune complex
      mediated, often with concurrent infections such as hepatitis B or C. Fibrillary
      glomerulonephritis (FGN), a rare primary glomerular disease, has only been
      reported in 2 HIV patients, and both patients had concurrent hepatitis C (HCV)
      infection. Here we report a unique case of FGN with unusual ultrastructural
      morphology in an HIV-positive African American patient without concurrent HCV
      infection. The patient presented with nephrotic range proteinuria and renal
      insufficiency. A percutaneous kidney biopsy showed mesangial and segmental
      endocapillary proliferative GN with crescent formation. Immunofluorescence
      studies revealed IgG-, kappa-, and C3-positive deposits in the mesangium and
      capillary loops. Electron microscopy demonstrated diagnostic features of FGN:
      randomly-arranged fibrillary deposits with a diameter of 15 - 30 nm. The deposits
      had an unusual distribution pattern of hump-like large deposits on the
      subepithelial aspect. Additionally, smaller deposits were also present in the
      mesangium. To our knowledge, this is the first reported case of FGN in an HIV
      patient without concurrent HCV infection.?.

PMID- 29578398
TI  - Variability of serum phosphorus and its association with mortality among
      hemodialysis patients?.
AB  - OBJECTIVE: To determine the relationship between the variability of serum
      phosphorus and mortality among maintenance hemodialysis (MHD) patients. MATERIALS
      AND METHODS: A total of 502 MHD cases were studied from the Shanghai Renal
      Registry Network. Serum phosphorus variability was indicated by a coefficient of
      variation (CV). According to the CV median of serum phosphorus, patients were
      divided into two groups: a high-variability group (CV >= 0.226 mmol/L) and a low
      variability group (CV < 0.226 mmol/L). Average phosphorus <= 1.78 mmol/L was
      defined as the standard phosphorus group and serum phosphorus > 1.78 mmol/L was
      defined as the non-standard phosphorus group. The relationship between serum
      phosphorus variability and all-cause and cardiovascular disease (CVD) mortality
      was assessed. RESULTS: In the 502 MHD cases, the average age of patients was 63.9
      +/- 14.60 years, and dialysis vintage was 82.0 (43.0 - 139.0) months. 118
      patients (23.5%) died, succumbing to all-cause mortality, while 64 patients
      (14.3%) died from CVD. The high-variability group had increased all-cause
      mortality (27.7% vs. 19.3%, p = 0.028). Death from CVD was increased in the high
      variability group, but had no statistical significance (15.4% vs. 10.0%, p =
      0.082). Cox regression analysis showed that older age, low hemoglobin levels, a
      higher phosphorus CV, and low serum albumin were independent risk factors for all
      cause and CVD mortality. The standard group with low-phosphorus variability had a
      decreased mortality compared with the non-standard group with high variability
      (15.3 vs. 29.2%, p = 0.047 and 6.0 vs. 15.0%, p = 0.033, respectively). The
      Kaplan-Meier method revealed that patients with low phosphorus variability had a
      decreased all-cause and CVD mortality (p = 0.023 and p = 0.047, respectively)
      compared with high phosphorus variability patients. CONCLUSION: Higher phosphorus
      CV was independently correlated with all-cause and CVD mortality. Low phosphorus
      variability with on-target levels resulted in decreased patient mortality. Thus,
      stable serum phosphorus levels may improve survival in MHD patients.?.

PMID- 29578399
TI  - Mini-review of kidney disease following hematopoietic stem cell transplant?.
AB  - Advancements in hematopoietic cell transplantation (HCT) have broadened
      indications for its use and resulted in more long-term survivors. Stem cell
      transplantation is associated with several well-known toxicities, although renal
      complications are not well defined. Acute and chronic kidney disease remains a
      common complication following transplantation itself. Incidence and risk factors
      for the development of chronic kidney disease (CKD) is less well understood.
      Recent estimates suggest that nearly 15% of subjects undergoing HCT will develop
      CKD, a complication that can progress to end-stage renal disease (ESRD), disrupts
      overall quality of life, and reduces overall survival. Several commonly-reported
      risk factors include acute kidney injury, graft-versus-host disease, and long
      term calcineurin inhibitor use. This review highlights the incidence, timeline,
      etiology, risk factors, and prognosis of kidney disease in the setting of
      hematopoietic stem cell transplantation. Investigation of the causes of CKD is
      needed, as are ways to prevent, mitigate, and treat kidney injury. Renal disease
      importantly reflects prognosis, with dialysis-requiring patients carrying greater
      than 80% mortality after 3 years. Although CKD following HCT is common,
      prospective studies are needed to confirm risk factors and better define the
      underlying mechanisms in order to promote therapies that prevent this
      complication.?.

PMID- 29578400
TI  - Incidence and timing of inadvertent nephrostomy catheter displacement in patients
      with ureteral obstruction?.
AB  - INTRODUCTION: To evaluate nephrostomy catheter displacement, we assessed the
      cumulative nephrostomy catheter displacement rate in patients with percutaneous
      nephrostomy and compared the nephrostomy displacement rates between pigtail and
      balloon catheters. MATERIALS AND METHODS: Between 2003 and 2011, 87 patients who
      underwent percutaneous nephrostomy catheter placement and more than one
      subsequent catheter replacement were retrospectively identified. We evaluated
      their inadvertent nephrostomy catheter displacement. RESULTS: 20 patients (23.0%)
      experienced incidental nephrostomy catheter displacement during the follow-up
      period. Kaplan-Meier analysis revealed that the 1-year nephrostomy catheter
      displacement-free survival rate was 62 +/- 9%. No significant independent risk
      factors for predicting nephrostomy catheter displacement were identified,
      including the type of catheter. The median time from initial placement to
      displacement of pigtail catheters was shorter than that of balloon catheters.
      CONCLUSION: There were no significant differences in the nephrostomy catheter
      displacement-free survival rates between the two types of catheters. Regardless
      of the type of catheter, our results indicated that careful handling and guiding
      during catheter placement are important for all patients because of the high risk
      of inadvertent events.?.

PMID- 29578401
TI  - Association between preoperative renin-angiotensin system inhibitor use and
      postoperative acute kidney injury risk in patients with hypertension?.
AB  - PURPOSE: To determine whether preoperative renin-angiotensin system (RAS)
      inhibitor use within 7 days of noncardiac surgery is associated with a lower
      incidence of postoperative acute kidney injury (AKI) in hypertensive patients.
      MATERIALS AND METHODS: We retrospectively analyzed 12,545 hypertensive patients
      undergoing noncardiac surgery at the Third Xiangya Hospital of Central South
      University from February 2007 to November 2015. According to the use of RAS
      inhibitors within 7 days of surgery, the patients were divided into a RASI group
      and a non-RASI group. We used a multivariable logistic regression model and
      propensity score matching (PSM) analysis to examine the association between
      preoperative RAS inhibitor use and postoperative AKI incidence. RESULTS: Among
      the 12,545 hypertensive patients undergoing noncardiac surgery who met the
      inclusion/exclusion criteria, 18.74% received preoperative RAS inhibitor
      treatment within 7 days of surgery. After PSM, 2,192 patients in each group were
      matched successfully. The incidence of postoperative AKI in the RASI group was
      significantly lower than that in the non-RASI group (7.39% vs. 12.32%, p <
      0.001). The multivariable logistic regression analysis and the PSM analysis
      demonstrated similar associations between preoperative RAS inhibitor use and
      postoperative AKI incidence. This association was modified by the presence of
      preoperative congestive heart failure (CHF) (p-value for the interaction: 0.027),
      and the observed association was not evident in patients without CHF (CHF:
      adjusted odds ratios (ORs): 0.47; 95% CI: 0.31 - 0.70 vs. no CHF: adjusted OR:
      0.80; 95% CI: 0.62 - 1.03). CONCLUSION: The preoperative use of RAS inhibitors in
      hypertensive patients was associated with a lower incidence of AKI following
      noncardiac surgery, and this association was not significant in the subgroup
      population without CHF.?.

PMID- 29578402
TI  - Chemotherapeutic agents eligible for prior dosing in pancreatic cancer patients
      requiring hemodialysis: a systematic review?.
AB  - AIMS: New chemotherapeutic agents prolong survival of patients with pancreatic
      ductal adenocarcinoma (PDAC). Although their incidence is rising, patients with
      end-stage renal disease (ESRD) requiring hemodialysis (HD) are not included in
      the phase III trials evaluating the effects of these chemotherapies. Many experts
      recommend applying chemotherapy after HD using a reduced dose. Alternatively, the
      concept of prior dosing allows for the application of dialyzable chemotherapeutic
      drugs using a normal dose, with an HD followed shortly after to mimic normal
      renal function. In this work, we provide guidance for clinicians on how to use
      chemotherapy in patients with PDAC on HD and how to identify substances suitable
      for prior dosing. MATERIALS AND METHODS: We systematically searched PubMed, from
      inception to September 2016, for published studies describing patients with ESRD
      on HD who received chemotherapies commonly applied in PDAC, including
      gemcitabine, fluorouracil (5-FU), capecitabine, oxaliplatin, irinotecan,
      docetaxel, erlotinib, sunitinib, S-1, and afatinib. Applied dosages, described
      toxicities, application time relative to HD, and pharmacokinetic measurements of
      the drug and its metabolites were assessed. Quantitative analysis of the drug
      plasma concentrations, including half-life during and in between HD and fraction
      of the drug eliminated during HD, were assessed. RESULTS: We identified 56
      studies describing 128 patients with ESRD undergoing HD during chemotherapeutic
      treatment. Quantitative pharmacokinetic analysis revealed that the following
      substances are dialyzable and thus suitable for application using the prior
      dosing method: gemcitabine, 5-FU, oxaliplatin, irinotecan, and S-1. CONCLUSION:
      This work supports the application of dialyzable chemotherapeutic agents in
      patients with PDAC in standard dose when HD is performed shortly after the
      infusion.?.

PMID- 29578403
TI  - Patient-reported outcomes (PROs) argue against the limited use of peritoneal
      dialysis in end-stage renal disease?.
AB  - AIM: Approximately 40% of dialysis patients are durably treated with peritoneal
      dialysis (PD) in our teaching hospital. Patients' perspectives were studied by
      patient-reported outcome measurements (PROMs) to find possible explanations for
      why the generally-reported decline in the use of PD hardly occurred in our
      facility. MATERIALS AND METHODS: All 75 prevalent adult dialysis patients
      hemodialysis (HD) duration 27, PD 16 months) were included. All had received
      predialysis care and education for > 6 month. Cross-sectional sociodemographic
      and clinical data, SF-36, KDQOL-SF, and predialysis anxiety/depression scores
      were collected in February 2016. Differences in PROMs between PD and HD patients
      were analyzed. RESULTS: Despite more comorbidity in the PD population, generally
      used dialysis parameters were adequate and similar between HD (n = 42) and PD (n
      = 33) patients as was annual mortality. Many factors associated with a
      predialysis modality choice for PD were absent. A higher anxiety/depression score
      was found in pre-HD compared to pre-PD patients. PROMs were returned by 97%. PD
      patients performed better on a number of PROMs than their HD counterparts.
      CONCLUSION: This single-center cross-section with a modest number of patients but
      an almost 100% patient response shows that having 40% of patients on PD is
      possible with excellent results in terms of patient-reported outcomes. A
      structured patient education with attention to personal needs of patients, an
      adequate infrastructure for PD, and a dedicated team with ongoing patient support
      are key factors. Sharing best practices may help to slow down or even reverse the
      decline of PD, which is a pity both for patients and society.?.

PMID- 29578404
TI  - Priapism and hemodialysis: Case report and literature review?.
AB  - BACKGROUND: Priapism is a known but rarely described complication of patients on
      dialysis. The incidence of priapism in the general population is estimated at 1.5
      in 100,000 patients and 2.9 in 100,000 patients in males over 40 years of age;
      however there is little current literature describing priapism in adult dialysis
      patients and no current literature in pediatric dialysis patients [1]. We
      describe two pediatric patients who developed priapism concurrent with
      hemodialysis, each with differing severity and therapeutic management. Case
      diagnosis/treatment: Two adolescent males presented with painful erection during
      a chronic hemodialysis treatment. Patient 1 required urologic intervention for
      management and treatment. Further medical treatment subsequently led to
      pseudoephedrine intoxication which self-resolved. Patient 2's priapism course
      self-resolved with adjustment in hemoglobin targets and did not require further
      surgical or medical intervention. Neither had recurrent episodes of priapism with
      careful management to maintain hemoglobin levels between 11 and 12 g/dL.
      CONCLUSION: Priapism is a rarely reported complication of dialysis in adult
      patients and has not been described in pediatric dialysis patients. The etiology
      remains unclear but is hypothesized to be multifactorial including heparin
      associated effects and epoetin administration. In our patients, commonality
      between the two included presumed high androgen levels (given age) and borderline
      to high hemoglobin levels in patients receiving epoetin alfa. This in combination
      with prior studies highlights the possible role epoetin administration may play.
      The role of heparin remains a possibility but is unclear. Further studies are
      needed to more clearly elucidate the etiology.?.

PMID- 29578405
TI  - NOTCH activity differentially affects alternative cell fate acquisition and
      maintenance.
AB  - The pituitary is an essential endocrine gland regulating multiple processes.
      Regeneration of endocrine cells is of therapeutic interest and recent studies are
      promising, but mechanisms of endocrine cell fate acquisition need to be better
      characterised. The NOTCH pathway is important during pituitary development. Here,
      we further characterise its role in the murine pituitary, revealing differential
      sensitivity within and between lineages. In progenitors, NOTCH activation blocks
      cell fate acquisition, with time-dependant modulation. In differentiating cells,
      response to activation is blunted in the POU1F1 lineage, with apparently normal
      cell fate specification, while POMC cells remain sensitive. Absence of apparent
      defects in Pou1f1-Cre; Rbpjfl/fl mice further suggests no direct role for NOTCH
      signalling in POU1F1 cell fate acquisition. In contrast, in the POMC lineage,
      NICD expression induces a regression towards a progenitor-like state, suggesting
      that the NOTCH pathway specifically blocks POMC cell differentiation. These
      results have implications for pituitary development, plasticity and regeneration.
      Activation of NOTCH signalling in different cell lineages of the embryonic murine
      pituitary uncovers an unexpected differential sensitivity, and this consequently
      reveals new aspects of endocrine lineages development and plasticity.

PMID- 29578406
TI  - Neurovascular sequestration in paediatric P. falciparum malaria is visible
      clinically in the retina.
AB  - Retinal vessel changes and retinal whitening, distinctive features of malarial
      retinopathy, can be directly observed during routine eye examination in children
      with P. falciparum cerebral malaria. We investigated their clinical significance
      and underlying mechanisms through linked clinical, clinicopathological and image
      analysis studies. Orange vessels and severe foveal whitening (clinical
      examination, n = 817, OR, 95% CI: 2.90, 1.96-4.30; 3.4, 1.8-6.3, both p<0.001),
      and arteriolar involvement by intravascular filling defects (angiographic image
      analysis, n = 260, 2.81, 1.17-6.72, p<0.02) were strongly associated with death.
      Orange vessels had dense sequestration of late stage parasitised red cells
      (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360
      degrees  of the lumen circumference, with altered protein expression in blood
      retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening
      was topographically associated with tissue response to hypoxia. Severe
      neurovascular sequestration is visible at the bedside, and is a marker of severe
      disease useful for diagnosis and management.

PMID- 29578407
TI  - Pauses in cholinergic interneuron firing exert an inhibitory control on striatal
      output in vivo.
AB  - The cholinergic interneurons (CINs) of the striatum are crucial for normal motor
      and behavioral functions of the basal ganglia. Striatal CINs exhibit tonic firing
      punctuated by distinct pauses. Pauses occur in response to motivationally
      significant events, but their function is unknown. Here we investigated the
      effects of pauses in CIN firing on spiny projection neurons (SPNs) - the output
      neurons of the striatum - using in vivo whole cell and juxtacellular recordings
      in mice. We found that optogenetically-induced pauses in CIN firing inhibited
      subthreshold membrane potential activity and decreased firing of SPNs. During
      pauses, SPN membrane potential fluctuations became more hyperpolarized and UP
      state durations became shorter. In addition, short-term plasticity of
      corticostriatal inputs was decreased during pauses. Our results indicate that, in
      vivo, the net effect of the pause in CIN firing on SPNs activity is inhibition
      and provide a novel mechanism for cholinergic control of striatal output.

PMID- 29578408
TI  - Differential 3' Processing of Specific Transcripts Expands Regulatory and Protein
      Diversity Across Neuronal Cell Types.
AB  - Alternative polyadenylation (APA) regulates mRNA translation, stability, and
      protein localization. However, it is unclear to what extent APA regulates these
      processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP,
      we discovered significant differences in APA between the principal types of mouse
      cerebellar neurons, the Purkinje and granule cells, as well as between
      proliferating and differentiated granule cells. Transcripts that differed in APA
      in these comparisons were enriched in key neuronal functions and many differed in
      coding sequence in addition to 3'UTR length. We characterize Memo1, a transcript
      that shifted from expressing a short 3'UTR isoform to a longer one during granule
      cell differentiation. We show that Memo1 regulates granule cell precursor
      proliferation and that its long 3'UTR isoform is targeted by miR-124,
      contributing to its downregulation during development. Our findings provide
      insight into roles for APA in specific cell types and establish a platform for
      further functional studies.

PMID- 29578409
TI  - Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure.
AB  - The ability of the Chagas disease agent Trypanosoma cruzi to resist extended in
      vivo exposure to highly effective trypanocidal compounds prompted us to explore
      the potential for dormancy and its contribution to failed drug treatments in this
      infection. We document the development of non-proliferating intracellular
      amastigotes in vivo and in vitro in the absence of drug treatment. Non
      proliferative amastigotes ultimately converted to trypomastigotes and established
      infections in new host cells. Most significantly, dormant amastigotes were
      uniquely resistant to extended drug treatment in vivo and in vitro and could re
      establish a flourishing infection after as many as 30 days of drug exposure.
      These results demonstrate a dormancy state in T. cruzi that accounts for the
      failure of highly cytotoxic compounds to completely resolve the infection. The
      ability of T. cruzi to establish dormancy throws into question current methods
      for identifying curative drugs but also suggests alternative therapeutic
      approaches.

PMID- 29578410
TI  - A conserved function for pericentromeric satellite DNA.
AB  - A universal and unquestioned characteristic of eukaryotic cells is that the
      genome is divided into multiple chromosomes and encapsulated in a single nucleus.
      However, the underlying mechanism to ensure such a configuration is unknown.
      Here, we provide evidence that pericentromeric satellite DNA, which is often
      regarded as junk, is a critical constituent of the chromosome, allowing the
      packaging of all chromosomes into a single nucleus. We show that the multi-AT
      hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1,
      play an evolutionarily conserved role in bundling pericentromeric satellite DNA
      from heterologous chromosomes into 'chromocenters', a cytological association of
      pericentromeric heterochromatin. Defective chromocenter formation leads to
      micronuclei formation due to budding from the interphase nucleus, DNA damage and
      cell death. We propose that chromocenter and satellite DNA serve a fundamental
      role in encapsulating the full complement of the genome within a single nucleus,
      the universal characteristic of eukaryotic cells.

PMID- 29578411
TI  - Dendritic spikes in hippocampal granule cells are necessary for long-term
      potentiation at the perforant path synapse.
AB  - Long-term potentiation (LTP) of synaptic responses is essential for hippocampal
      memory function. Perforant-path (PP) synapses on hippocampal granule cells (GCs)
      contribute to the formation of associative memories, which are considered the
      cellular correlates of memory engrams. However, the mechanisms of LTP at these
      synapses are not well understood. Due to sparse firing activity and the voltage
      attenuation in their dendrites, it remains unclear how associative LTP at distal
      synapses occurs. Here, we show that NMDA receptor-dependent LTP can be induced at
      PP-GC synapses without backpropagating action potentials (bAPs) in acute rat
      brain slices. Dendritic recordings reveal substantial attenuation of bAPs as well
      as local dendritic Na+ spike generation during PP-GC input. Inhibition of
      dendritic Na+ spikes impairs LTP induction at PP-GC synapse. These data suggest
      that dendritic spikes may constitute a key cellular mechanism for memory
      formation in the dentate gyrus.

PMID- 29578412
TI  - Cytokine receptor-Eb1 interaction couples cell polarity and fate during
      asymmetric cell division.
AB  - Asymmetric stem cell division is a critical mechanism for balancing self-renewal
      and differentiation. Adult stem cells often orient their mitotic spindle to place
      one daughter inside the niche and the other outside of it to achieve asymmetric
      division. It remains unknown whether and how the niche may direct division
      orientation. Here we discover a novel and evolutionary conserved mechanism that
      couples cell polarity to cell fate. We show that the cytokine receptor homolog
      Dome, acting downstream of the niche-derived ligand Upd, directly binds to the
      microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila
      male germline stem cells (GSCs). Dome's role in spindle orientation is entirely
      separable from its known function in self-renewal mediated by the JAK-STAT
      pathway. We propose that integration of two functions (cell polarity and fate) in
      a single receptor is a key mechanism to ensure an asymmetric outcome following
      cell division.

PMID- 29578413
TI  - Erratum to 'Improvement of intestinal absorption of curcumin by cyclodextrins and
      the mechanisms underlying absorption enhancement' [Int. J. Pharm. 2018, 535, 340
      349].

PMID- 29578414
TI  - A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral
      Nerves.
AB  - A wireless electrical stimulation implant for peripheral nerves, achieving >10*
      improvement over state of the art in the depth/volume figure of merit, is
      presented. The fully integrated implant measures just 2 mm * 3 mm * 6.5 mm (39
      mm3, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The
      implant is powered using ultrasound and includes a miniaturized piezoelectric
      receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy
      storage capacitor, and platinum stimulation electrodes. The package also includes
      an optional blue light-emitting diode for potential applications in optogenetic
      stimulation in the future. A system-level design strategy for complete operation
      of the implant during the charging transient of the storage capacitor, as well as
      a unique downlink command/data transfer protocol, is presented. The implant
      enables externally programmable current-controlled stimulation of peripheral
      nerves, with a wide range of stimulation parameters, both for electrical (22 to
      5000 MUA amplitude, ~14 to 470 MUs pulse-width, 0 to 60 Hz repetition rate) and
      optical (up to 23 mW/mm2 optical intensity) stimulation. Additionally, the
      implant achieves 15 V compliance voltage for chronic applications. Full
      integration of the implant components, end-to-end in vitro system
      characterizations, and results for the electrical stimulation of a sciatic nerve,
      demonstrate the feasibility and efficacy of the proposed stimulator for
      peripheral nerves.

PMID- 29578415
TI  - [ENDOTHELIAL DYSFUNCTION AND MICROSCIRCULATION FEATURES IN PATIENTS WITH HIGH
      RISK OF DEVELOPMENT OF REPERFUSION SYNDROME IN CONDITIONS OF RECONSTRUCTION
      ARTERIAL OPERATIONS].
AB  - Aim - to study the state of the microcirculatory bed and the endothelial system
      in patients at risk of developing reperfusion syndrome and suggest methods for
      their correction. The work included 29 patients with obliterating diseases of the
      abdominal aorta and lower limb arteries with a high risk of developing
      reperfusion complications. Two groups of patients were identified. Group I - 8
      patients, preoperative preparation include the generally accepted approaches.
      Group II - 21 patients whose preoperative preparation included, in addition to
      preparations for improving rheological blood conditions, prolonged epidural
      anesthesia, intravenous injection of hydroxyethylstarches, korvetin and
      alprostadil. In patients of both groups, a study was made of the state of the
      level of endothelial dysfunction, changes in capillary blood flow and arterio
      venular blood shunting. Revascularization of the lower limbs in patients with a
      high risk of developing reperfusion complications leads to a deepening of
      endothelial dysfunction. The latter is characterized by a 2.3-fold increase
      (p<0.001) in the early postoperative period of circulating endothelial cells in
      the blood, by 2.5 times (p <0.001) endothelin-1, while a 1.3-fold decrease
      (p<0,05) P-selectin and in 1,7 times (p<0,05) E-selectin. The depth of the lesion
      of the endothelial system is indicated by a decrease of 29.9 % (p<0.001) in the
      level of NO. Deepening of endothelial dysfunction after reconstructive
      reconstructive surgery is reflected in violations of the function of the
      microcirculatory bed. It is characterized by a 1.9-fold decrease (p<0.001) of
      skin perfusion, 2.0 times (p<0.001) in the erythrocyte concentration index and a
      14% decrease (p<0.05) in capillary blood flow. This is facilitated by an increase
      of 14% (p<0.05) in skin perfusion pressure and an increase of 16% (p<0.05) in the
      resistance index of the microcirculatory bed, which leads to a decrease in tissue
      oxygenation to a level 3.38+/-0.14 mm.hg.

PMID- 29578416
TI  - [DISTANT CONSEQUENCES AND THE QUALITY OF LIFE OF PATIENTS WITH MILITARY-RELATED
      CRANIOCEREBRAL TRAUMA].
AB  - The purpose of the study was to determine appropriate diagnostic, therapeutic and
      rehabilitation treatments of patients with military-related craniocereberal
      trauma. We have examined 180 male patients: 100 participant of operations in the
      Democratic Republic Afghanistan (1979-1989) and 80 - participants of conflict in
      the east of Ukraine (from 2014 until present) with military-related
      craniocereberal trauma of varying severity. We used clinical-neurological,
      instrumental (craniography of skull, magnetic resonance imaging, ultrasonic
      doppler sonography of the main vessels of the head and neck), biochemical,
      statistical methods of a research, and also questionnaire scale SF-36. It was
      found that the quality of life of patients with military-related craniocereberal
      trauma depends on the severity of the wound and the period after trauma. In the
      early period after military-related craniocereberal trauma of light or average
      severity, the psychological components are more strongly manifested. Patients
      with severe military-related craniocereberal trauma have serious physical,
      psychological and social problems at different periods after trauma. The results
      of the research show that the quality of life depends on the severity of
      functional disorders and have impact on adaptive potential of the organism.

PMID- 29578417
TI  - RELATIONSHIP BETWEEN GENERAL HEALTH, ORAL HEALTH AND HEALTHY LIFESTYLE IN ELDERLY
      POPULATION (REVIEW).
AB  - This literature review aims to investigate how a poor oral health impacts on
      general health and healthy lifestyle of elderly people. The literature review was
      performed using ScienceDirect, Scopus and PubMed databases to identify relevant
      published studies. The year of publication was limited to over the past 5 years
      and the language was limited to English. Having considered the relevant articles'
      abstracts the 36 articles were selected. Systematical literature revision shows
      that recently, the older population has increased worldwide and it is being
      predicted to keep growing in near future. As age-related changes are observed in
      oral cavity, geriatric dentistry becomes more relevant to investigate oral
      disorders and to take relevant measures in elderly population. There is an urgent
      need to clarify the correlations between oral and general health. Unsatisfactory
      oral conditions lead to serious systemic diseases. Based on the currently
      available evidence, better collaboration between medical and dental fields is
      required in order to create and maintain healthy elderly population. A special
      association with professional group is important for implementation of new
      programs, in order to enhance and maintain satisfactory oral hygiene, oral health
      and oral health related quality of life.

PMID- 29578418
TI  - [TRANSOSSEOUS OSTEOSYNTHESIS OF LOWER EXTREMITIES BONES FRACTURES AND QUALITY OF
      LIFE OF PATIENTS IN THE TREATMENT PERIOD].
AB  - The aim of the study is a comparative analysis of the quality of life in the
      treatment of fractures of the bones of the lower extremities of various
      localizations using transosseous and submerged osteosynthesis. We examined 397
      patients with injuries of the lower segment of the lower extremity (patellar
      fractures - 81, multiple bones fractures of the tibia - 84 and fractures of the
      ankles, accompanied by a dislocation of the foot - 232). Patients were
      distributed in the subgroups depending on the treatment. The main group was
      performed using transosseous osteosynthesis, the comparison group - submerged
      osteosynthesis. The quality of life was examined using a general questionnaire SF
      36 and specialized KOOS (with patella fractures) and FOAS (fractures of the bones
      of the lower leg and ankles). In patients with all localizations of fractures the
      quality of life was exceeded in the subgroups of the transosseous osteosynthesis
      group over the parameters of the comparison group. The most significant
      differences with the use of specialized questionnaires were revealed 6-9 months
      after trauma with a tendency to leveling to the end of the study (1 year). A more
      pronounced excess of the quality of life in the main group was seen in fractures
      of the shin bones. The study of the quality of life allows us to recommend the
      use of transosseous osteosynthesis for the treatment of lower segment of the
      lower limb bone fractures.

PMID- 29578419
TI  - [THE CONDITION OF THE CERVIX IN WOMEN LIVING IN OIL AND GAS BEARING AREAS].
AB  - The aim of the study was to determine the influence of oil products on the
      development of cervical pathology in women living in oil and gas bearing areas. A
      retro and prospective study of 300 women was conducted, of which 150 studied -
      Temir district (main group) and 150 women of Khobdinsky district (control group).
      It was revealed that a complex of unfavorable environmental factors affecting the
      body of women living in the oil and gas bearing area leads to deterioration of
      gynecological health and development of the precancerous process of the cervix:
      in women of the main group, under constant exposure to harmful factors,
      significantly more often than in women in the control group reveals precancerous
      conditions of the cervix of varying severity -28 (18.6%) and 9 (6%). Vaginal
      contents in women of the main group are characterized by significant disturbances
      in the microbial flora, which is manifested by a significant increase in the
      number of strict anaerobic bacteria, 69-46% and 31-20.6%, as compared with the
      control group. The increased generation of anaerobes is accompanied by a decrease
      in the frequency of lactobacilli, in particular lactobacilli, which in turn can
      lead to a disruption of the normal epithelization of the cervix.

PMID- 29578420
TI  - [CORRELATION OF ANTI-MULLERIAN HORMONE WITH HORMONAL AND OVARIAN MORPHOLOGICAL
      CHARACTERISTICS IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME WITH AND WITHOUT
      INSULIN RESISTANCE].
AB  - PCOS has a leading place in women's infertility. Based on the data of recent
      researches, Anti-Mullerian hormone (AMH) has been considered as one of the
      diagnostic criteria for PCOS. The aim of study was to determine the correlation
      of Anti-Mullerian hormone with hormonal and ovarian morphological characteristics
      in patients with PCOS, with and without insulin resistance. 110 women with
      diagnosis of PCOS were involved in the study. Patients were divided into two
      groups: PCOS patients with insulin resistance (60 women) and PCOS patients
      without insulin resistance (50 women). All patients underwent hormonal
      investigation (AMH, FSH, LH, T, FT, HOMA- IR, FAI and SHBG). The volume of
      ovaries and the number of antral follicles (AFC) were determined by ultrasound
      imaging. Sorrelation between AMH and the ovarian hormonal and morphological
      characteristics has been shown. In particular, a significant positive correlation
      between AMH and the volume of the ovaries in both groups was demonstrated. In the
      group of patients with PCOS and insulin resistance a positive correlation between
      AMH and the volum of ovary, AFC was shown, as well as a negative correlation
      between AMH and SHBG. In the same group a tendency of the positive correlation
      between AMH and TT, HOMA-IR and IRI was seen. In the group of patients with PCOS
      without insulin resistence a positive correlation between AMH and the volum of
      ovary was observed, as well as the tendency of positive correlation between AMH
      and AFC, TT, HOMA-IR, IRI. Additionally, a negative correlation between AMH and
      SHBG was seen in the later patient group. Increased levels of AMH in all PCOS
      patients in our study, in comparison with the accepted norm, indicates on
      possibility of using this data in the diagnosis of PCOS. AMH levels in PCOS
      patients with and without insulin resistance do not differ significantly. The
      correlation between AMH and the morphological characteristics of ovaries has been
      established.

PMID- 29578421
TI  - THE DIAGNOSTIC VALUE OF OSTEOPONTIN AS AN EARLY MARKER OF PILMONARY HYPERTENSION
      AFFECTED BY CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND CONCOMITANT ISCHEMIC HEART
      DISEASE.
AB  - The article highlights the results of the study of the influence of osteopontin
      on the development of pulmonary hypertension in patients with COPD in combination
      with IHD. 121 patients with established diagnosis of COPD and IHD were randomized
      for the study, all patients underwent general clinical examination, spirography,
      ECG to determine the level of pulmonary artery pressure, a questionnaire
      according to the Borg and mMRC scales, and a 6-minute walk test. All patients
      were divided into 2 groups: group 1 (63 people) with the increased PA pressure,
      group 2 - comparison group - without PH (58 people). The conducted study suggests
      that the concentration of circulating osteopontin above 38.25 ng/ml can be
      considered as an early marker and an independent predictor of pulmonary
      hypertension in patients with COPD and concomitant IHD. In the PH (main) group
      osteopontin statistically significantly positively correlated with the age of
      patients, the right atrial area and the plasma level of interleukin 2 (IL-2).
      Interleukin 4 (IL-4), which is a marker of anti-inflammatory plasma activity,
      does not correlate with either pulmonary hypertension or osteopontin level, which
      indicates insufficient.

PMID- 29578422
TI  - [EFFECT OF VIOLATIONS OF CARBOHYDRATE METABOLISM ON THE LEVELS OF BIOMARKERS OF
      INFLAMMATION OF P-SELECTIN AND GALECTIN-3 IN PATIENTS WITH STABLE ANGINA].
AB  - The aim of the study was to study the effect of carbohydrate metabolism
      disturbances and other factors on the level of new biomarkers of P-selectin and
      Galectin-3 inflammation in patients with stable angina. The study included 119
      patients with angina with or without diabetes mellitus, as well as patients with
      type 2 diabetes. Patients included in the study were tested in addition to
      standard methods to determine the levels of new biomarkers of inflammation of P
      selectin, Galectin-3 and hs-CRP. The data obtained showed that the levels of P
      selectin and Galectin-3 in patients with stable angina are interrelated, but vary
      significantly at the individual level, with both biomarkers of inflammation not
      associated with hs-CRP, which creates the prerequisites for the personalization
      of therapeutic goals in reducing the systemic inflammatory response. A higher
      level of P-selectin in a subgroup of patients with stable angina with concomitant
      diabetes mellitus was revealed in comparison with the subgroup of patients with
      DM without angina (119.9+/-30.1 and 79.3+/-38.2 ng/ml, p<0.05, respectively). P
      selectin is linked at the level of glycosylated hemoglobin (correlation
      coefficient = 0.256, p=0.043) and disorders of carbohydrate metabolism. However,
      the presence of myocardial ischemia influences the activation of the platelet
      component of inflammation to a greater extent. Galectin-3 was also linked
      according to the correlation analysis with violations of carbohydrate metabolism.
      The levels of P-selectin and Galectin-3 in the plasma of patients with angina
      pectoris were influenced by sex, age of patients and age at which angina was
      first diagnosed. However, the greatest effect on P-selectin and Galectin-3 levels
      was exerted by the degree of coronary atherosclerosis and the severity of angina
      pectoris according to loading test data.

PMID- 29578423
TI  - IMPACT OF RADIOFREQUENCY CATHETER ABLATION ON HEALTH-RELATED QUALITY OF LIFE
      ASSESSED BY THE SF-36 QUESTIONNAIRE IN PATIENTS WITH PAROXYSMAL SUPRAVENTRICULAR
      TACHYCARDIA.
AB  - The aim of the study was to investigate the effect of catheter ablation on
      different aspects of health-related quality of life in association with patients'
      age, gender and the type of paroxysmal supraventricular tachycardia. We
      investigated 70 consecutive patients with paroxysmal supraventricular tachycardia
      (AV Nodal Reentrant Tachycardia (AVNRT), AV Reentrant Tachycardia (AVRT) or
      Atrial Tachycardia (AT)) who underwent a catheter ablation. The patients were
      asked to fill out the short form (SF-36) health questionnaire before the ablation
      on the day of the procedure and after 3 months of a successful catheter ablation
      and eight health concept scores (1. Physical functioning; 2. Role limitations due
      to physical health; 3. Role limitations due to emotional problems; 4.
      Energy/fatigue; 5. Emotional wellbeing; 6. Social functioning; 7. Bodily pain;
      and 8. General health) were assessed before and after ablation. All health
      concept scores improved significantly after successful catheter ablation
      procedure. The result for the whole group were as follows: 1. physical
      functioning improved from mean 61.42+/-24.82 to 77.15+/-18.80 (p<0.001). 2. Score
      for the role limitations due to physical health improved from 41.78+/-39.17 to
      75.35+/-33.91 (p<0.001). 3. Score for the role limitations due to emotional
      problems improved from 48.07+/-42.32 to 80.46+/-33.81 (p<0.001). 4.
      Energy/Fatigue score improved from 56.71+/-19.97 to 68.78+/-16.40 (p<0.001). 5.
      Emotional wellbeing score improved from 58.22+/-17.31 to 71.88+/-14.33 (p<0.001).
      6. Social functioning score improved from 68.39+/-24.51 to 81.00+/-19.12
      (p<0.001). 7. Pain score improved from 59.82+/-28.65 to 80.57+/-20.58 (p<0.001)
      and 8. General health score improved from 48.42+/-15.26 to 62.57+/-15.43
      (p<0.001). This study shows that catheter ablation which can effectively cure the
      patients from the paroxysmal supraventricular tachycardia significantly improves
      physical, emotional and social health scores by eliminating the arrhythmia
      episodes and associated symptoms and anxiety in patients with paroxysmal
      supraventricular tachycardia irrespective of patient demographics and the type of
      the SVT.

PMID- 29578424
TI  - INFLUENCE OF CATHETER ABLATION OF PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA ON
      PATIENTS' ANXIETY.
AB  - The aim of the study was to investigate the influence of catheter ablation of
      paroxysmal supraventricular tachycardia on patients' anxiety levels. We
      investigated 70 consecutive patients with paroxysmal supraventricular tachycardia
      (AV Nodal Reentrant Tachycardia (AVNRT), AV Reentrant Tachycardia (AVRT) or
      Atrial Tachycardia (AT)) who underwent a catheter ablation. The patients filled
      out the State and Trait Anxiety Inventory (STAI) before the ablation on the day
      of the procedure and after 3 months of a successful catheter ablation. State and
      trait anxiety scores were compared before and after 3 months of ablation. The
      results were analyzed between different age (<50 vs >=50 y), gender and the type
      of paroxysmal supraventricular tachycardia (AVNRT vs AVRT/AT). Both state and
      trait anxiety scores improved significantly after catheter ablation. State
      anxiety score improved from mean 42.21+/-9.53 to 31.43+/-8.02 (p<0.001). Trait
      anxiety score improved from mean 45.76+/-7.80 to 39.80+/-7.33 (p<0.001). Present
      study demonstrates that the radiofrequency catheter ablation of paroxysmal
      supraventricular tachycardia by providing cure and eliminating the arrhythmia
      episodes significantly reduces both situational and general anxiety levels.

PMID- 29578425
TI  - NEW APPROACHES IN THE DIAGNOSTIC OF ICHTHYOSIS DISORDERS.
AB  - The aim of this study was to study the macroscopic changes in the skin of
      patients with various forms of ichthyosis to improve and optimize treatment. A
      comprehensive examination of 12 patients with ichthyosis under the supervision of
      a dermatovenereologist was conducted at VOKSHVD. For the diagnosis of macroscopic
      skin changes, the dermatoscopy was performed by the HEINE DELTA 20 (r) (Germany)
      apparatus, the results were recorded with a Canon 550D camera (Japan) at 1:35 or
      1:30, with a sensitivity of IZO 200 using an adapter included with the
      dermatoscope. All affected skin were examined, which were compared with unharmed
      ones. The task was performed using the algorithm developed by us for
      dermatoscopic assessment of the severity of ichthyosis. The presence of typical
      dermatoscopic signs in examined patients with ichthyosis, which is manifested by
      the smoothness of the skin pattern, the presence of a pseudo-pigmental mesh,
      formed by keratin of scales in the form of lines, mesh and loop structures
      resembling cerebriform components, are established. The algorithm of estimation
      of expressiveness of dermatoscopic features for patients with light and severe
      clinical course of ichthyosis is proposed. Also, specific dermatological signs
      were observed in the mild clinical course of ichthyosis, in particular the
      phenomenon of "sparkling champagne", and in severe clinical course, the "melting
      ice" phenomal. The use of the dermatoscopic method makes it possible to
      objectively evaluate the severity of the ichthyosis and apply a differentiated
      approach to choosing the most effective treatment schemes.

PMID- 29578426
TI  - DYSFUNCTION OF VARIOUS ORGAN SYSTEMS INDUCED BY SEPSIS WITH UNDERLYING SEVERE
      MYELOMIC DISEASES AND PROSTATE CANCER (CASE REPORT).
AB  - A 65-year-old male patient, unconscious, was admitted into the clinic by the
      Ambulance. From the patient's medical history it was revealed that several hours
      before the admission in the clinic the following symptoms were present: shortness
      of breath, fever, hypotonia, consciousness inhibition, because of which emergency
      brigade was called and was brought by the Emergency Brigade. The history is
      loaded by chronic pathologies: myeloma disease, prostate cancer, ciliary
      arrhythmia, heart failure; received several courses of polichemotherapy, last ten
      days has been treated for pneumonia with antibiotics of ceftriaxone group in
      outpatient setting. It is also noteworthy that for the last three months
      dysfunction of musculoskeletal system with muscle weakness, restricted motion has
      been present. Clinically there was present dysfunction syndrome of several
      organs: disorder of function of several organs that required emergency
      intervention, recovery chance was very low, correlation with morbidity in PIRO
      was high. By investigation it is known, that as SIRS aggravates, and turns into
      septic shock, lethal index increases, especially when the underlying severe
      diseases are present. On basis of certain data we can conclude that the severity
      of the disease may have some compatibility with results, although it is
      alteration of further clinical status of initial stage that has the closest
      compatibility with results. Sepsis toward MODS experiences progress with lethal
      results. Mortality rate in the patients with acute respiratory deficiency
      increases from 50% to 80%. In most patients with sepsis syndrome, who have 3 or
      more organs damaged, lethality is more than 90%. In this certain case organ
      systems that are mostly involved in the process during the sepsis, are
      respiratory, blood, renal and cardiovascular systems, were all involved , in the
      mentioned case a reasonable symptomatic and pathognomic treatment and the
      appropriate measures led to the recovery of the above mentioned patient. Sepsis
      syndrome is developed when the balance between the substances that contribute to
      the inflammation and anti-inflammatory substances is violated. By the mentioned
      case there is sepsis - induced polyorganic insufficiency with underlying severe
      somatic pathological condition, with violation of hemodynamics. Clinically the
      insufficiency of all the organic systems developed at the background of cardio
      respiratory-cerebral insufficiency, with functional insufficiency of all the
      organ systems and violation of buffer system. With reasonable pathognomic and
      symptomatic treatment eradication of vicious circle was possible. The patient was
      discharged from the clinic with positive clinic-laboratory recovery. The
      condition is stable. Neurological status -contact, adequate, with high capacity
      to work, and with an achievement of 2 year remission.

PMID- 29578427
TI  - EVALUATION OF EFFICIENCY OF IMIGLUCERASE (CEREZYME) IN THE TREATMENT OF GAUCHER
      DISEASE (CASE REPORTS AND REVIEW OF THE LITERATURE).
AB  - The data on occurrence and pathogenetic mechanisms of glucosylceramide lipidosis
      (Gaucher disease), which is based on the hereditary deficiency of
      glucocerebrosidase activity -the enzyme involved in the processing of cellular
      metabolism products, is presented. Clinical and morphological manifestations of
      the disease, therapeutic tactics and prognosis are defined. A typical clinical
      case of Gaucher disease type 1 in two adult patients was analyzed. It is shown
      that timely diagnosis of Gaucher disease allows the prescription of adequate
      treatment by means of enzyme replacement therapy with cerezyme drug. That is why
      the correct and timely diagnosis of the disease can prolongate patient's life for
      many years. In this case, the patient should be under the care of doctors
      (pediatricians, general physicians, hematologists). Continued treatment of
      Gaucher disease with cerezyme stabilizes the pathological process completely,
      decreases significant changes in bones and parenchymal organs, improving
      patients' lives considerably. For that reason, the sooner the adequate therapy is
      started, the more effective the results will be.

PMID- 29578428
TI  - UNILATERAL FRONTALIS MUSCLE PARALYSIS: MANAGEMENT WITH BOTULINUM TOXIN A (CASE
      REPORTS).
AB  - Unilateral frontalis muscle palsy is a debilitating disease with a heterogeneous
      etiology. Congenital or acquired unilateral paralysis of the frontalis muscle
      causes ipsilateral brow ptosis and contralateral hypermobility of the non
      paralytic frontalis muscle, resulting in a bizarre asymmetry and emotional
      embarrassment. We present five patients with unilateral frontal muscle paralysis,
      two males and three females, aged between 32 and 68, treated with botulinum toxin
      A injection to the contralateral (non-affected) side. A total dose between 10 to
      30 U botulinum toxin A (onabotulinum or incobotulinum toxin A) successfully
      improve symmetry and facial esthetics without any adverse events. Botulinum toxin
      A is an alternative to facial palsy surgery but may also be used as an adjunct
      after the surgical procedure to optimize the outcome.

PMID- 29578429
TI  - KERATOACANTHOMA OF THE UPPER LIP: REVIEW OF THE LITERATURE AND REPORT OF CASE
      WITH CENTRAL UPPER LIP RECONSTRUCTION.
AB  - Keratoakanthoma (KA) is a common non-melanoma skin tumor of sun-exposed skin.
      Recently it has been classified as a highly differentiated squamous cell
      carcinoma, based on the evidence of local destruction, tissue invasion and
      malignant transformation with metastatic spread described in the medical
      literature. Lower lip KA is not uncommon on lower lip, and quite rare on upper
      lip. The authors present a case of 78-year-old Caucasian male patient with a
      rapidly growing keratotic tumor of the central region of upper lip. After
      complete surgical excision, single-stage reconstruction of the defect was
      performed by modified Goldstein's bilateral advancement myocutaneous vermilion
      flap. The histologic examination confirmed KA with excision margins within
      healthy tissue. Healing was unremarkable and functional and esthetic outcomes
      were very good. KA of the upper lip is a rare tumor that warrants complete
      surgical excision. Reconstruction of the central part of the upper lip is a
      challenge, but bilateral advancement myocutaneous vermilion flap resulted in good
      outcome.

PMID- 29578430
TI  - DEVELOPMENT OF GANGLIONOPATHY AND TABETIC VISCERAL CRISES ON THE BACKGROUND OF
      POLYRADICULONEUROPATHY ASSOCIATED WITH MONOCLONAL GAMMOPATHY (CASE REPORT).
AB  - The article presents an analysis of the clinical occurrence of development of
      chronic polyradiculoneuropathy associated with monoclonal IgG/k (kappa)
      gammopathy of the undetermined significance. The peculiarity of this occurrence
      is the uniqueness of the development of the symptoms which are characteristic of
      tabes dorsalis in this pathology with episodic severe visceral crises and also
      with ganglionopathy. The example describes the clinical polymorphism of the
      course of visceral crises, the problems of their diagnosis and as a consequence
      of inadequate treatment with the development of severe social maladaptation. The
      importance of timely diagnosis and treatment of such conditions is discussed.

PMID- 29578431
TI  - [CASE REPORT OF CANDIDA PNEUMONIA].
AB  - Fungal pneumonia is considered as one of the most serious forms of pneumonia, the
      number of which has recently increased despite the use of new antimycotic drugs
      in pulmonology. Specificity of pathogens and torpid current of pneumomycosis
      represent great difficulties for accurate diagnosis and delay the timely onset of
      therapy, exacerbating inflammatory changes. In this article we present a rare
      case of isolated infection of the lungs parenchyma with Candida albicans in the
      form of focal pneumonia of the right lung lower lobe complicated by a clotted
      pleurisy. Patient is eighteen-year-old young man who is currently finding in the
      army. Our attention was attracted the fact that he was hospitalized twice within
      the 4 months with the same diagnosis - fungal pneumonia. At the same time, the
      localization of the process was the same as in the previous hospitalization. In
      this article, we tried to understand the reasons of unsuccessful treatment of
      this pathology. And we came to the following conclusions that the reason of
      repeated hospitalization of this patient was the short stay in the hospital and
      the duration of the diagnostic tests. Bacteriological examination of sputum takes
      about 5-7 days on average, which led to untimely started treatment. A short
      period of hospitalization, regulated by the protocols of diagnosis and treatment,
      contributed to inadequate treatment of this pathology. Thus, today there is a
      definite demand for the development of rapid diagnostic tests of fungal pneumonia
      and new protocols for diagnosis and treatment, taking into account the duration
      of treatment for Candida infection.

PMID- 29578432
TI  - TREATMENT OF PYOINFLAMMATORY COMPLICATIONS WITH INDIVIDUALLY SELECTED OZONE DOSE
      IN PATIENTS WITH DIABETES.
AB  - The severity of purulent-inflammatory process in patients with diabetes mellitus
      is determined by lymphocytotoxic test. The test shows that application of
      intravenous ozone therapy with individually selected ozone dose significantly
      decreases the spread of necrotic suppurative focus already on the third day of
      treatment. Granulation tissue and marginal epithelization in the wound develops
      on the 6-8th day of hospitalization; normalization of glycemic levels shorten of
      the period of the hospital stay up to 3-5 days, compared to the control group.

PMID- 29578433
TI  - [THE ROLE OF SOME VAZOACTIVE PEPTIDES IN THE PATHOGENESIS OF EARLY FORMES OF
      ROSACEA AND THE HEMOSTASIS SYSTEM].
AB  - Recently, the role of vasoactive peptides has been increasingly discussed in the
      pathogenesis of rosacea. The most attention is paid to the growth factor of the
      vascular endothelium (VEGF). VEGF affects angiogenesis and survival of immature
      blood vessels. Cytokine contributes to an increase in the level of IL-8, which
      plays a role in the development of inflammation. VEGF is synthesized by activated
      keratinocytes as a result of various factors. In particular, after exposure to
      ultraviolet irradiation, the production of cytokines-IL-1 and TNF-alpha-is
      provoced, which stimulate keratinocytes to synthesize of VEGF. The latest data on
      the state of the coagulation system in rosacea patients indicate a shift in the
      functional activity of the hemostasis system toward hypercoagulability. The aim
      of the study was to study the relationship between changes in the concentration
      of certain vasoactive peptides and the parameters of the hemostasis system in
      patients with rosacea. The state of the hemostasis system was assessed by
      prothrombin and thrombin time. The content of fibrinogen, fibrinolytic activity
      of blood, and also prothrombin index were determined as well. The concentration
      of free VEGF, IL-8 in the serum was determined by the method of enzyme
      immunoassay In the study, patients with rosacea, according to their age, were
      divided into 2 groups: -I group - patients aged 35 to 45 years, II group -
      patients aged 45 to 65 years. As the results of the study showed, the
      concentration of vasoactive peptides in patients with various clinical forms of
      rosacea differs significantly from those in the control group. In patients with
      various clinical forms of rosacea, the tendency of changes in all parameters
      (thrombin time, prothrombin time, fibrinogen, prothrombinic index) of the state
      of the coagulating system of blood with the manifestation of hypercoagulability
      is traced. And if the change in the content of cytokines was observed equally
      often in all observed patients, the manifestations of hypercoagulability were
      most pronounced in the second group of patients (aged 45 to 65 years) Thus, the
      results of the study allow us to conclude that an increase in the concentration
      of cytokines (which are a potent provoker of changes in permeability, atony and
      brittleness of the vessel walls), as well as hypercoagulable phenomena,
      indicative of ongoing microcracking processes, are the leading links in the
      pathogenesis of early forms of rosacea.

PMID- 29578434
TI  - POST-TRAUMATIC STRESS DISORDER AND COMORBIDITY: THE ROLE OF MEDIATION AND
      RELATION BETWEEN PTSD AND SOMATIC COMPLAINTS IN MENTAL HEALTH MANAGEMENT.
AB  - Several studies have demonstrated the relationship between PTSD, somatic
      symptoms, and the role of co-morbid depression and anxiety. A study was conducted
      to test whether symptoms of PTSD influence somatic complaints indirectly through
      underlying symptoms of depression and anxiety. The participants included 69
      veterans following a 6-month deployment and who showed criteria for probable PTSD
      diagnosis. Data were collected in 2014 and 2015. Measures included the PTSD
      checklist (PCL-5) and subscales of the Patient Health Questionnaire (PHQ),
      including anxiety disorder, depression, and somatic complaints. Depressive
      symptoms, as well as anxiety symptoms, had significantly mediated the
      relationship between PTSD and somatic complaints and positively related to
      somatic symptom severity. Otherwise, depression is a more robust factor than
      anxiety. Both severities of anxiety and severity of depression were more strongly
      associated with somatic complaints than PTSD itself. These new findings may have
      implications for the management of PTSD treatment in Military mental health
      services as well as in public health management since it recognizes the
      importance of Comorbid depression and anxiety when somatic complaints are
      present.

PMID- 29578435
TI  - [THE ROLE OF MARKER FIBROSIS ST2 AND ANGIOTENZINOGEN GENE POLYMORPHISM IN HEART
      FAILURE PROGRESSING IN PATIENTS WITH TYPE 2 DIABETES MELLITUS].
AB  - Despite the progress in the treatment of HF, its prognosis remains disappointing
      primarily due to the fact that important subgroups of patients with HF are not
      sufficiently investigated. This also applies to patients with HF and background
      metabolic disorders, in particular, type 2 diabetes. It is known that the
      polymorphism of the rs699 marker of the M235T ATG gene is associated with a
      tendency to arterial hypertension, coronary heart disease and atrial
      fibrillation. A relationship was found between the polymorphism of M235T and the
      risk of HF development. One of the promising new biomarkers is the fibrosis
      marker ST2. The purpose of our study was to evaluate the role of the biomarker
      ST2 and the genetic polymorphism of the AT2 gene M235T in the progression of CHF
      and the development of adverse events in patients with concomitant type 2
      diabetes. We found that patients with HFpEF and T2DM with ATG TT + MT genotype
      have a higher level of ST2 and a higher probability of unfavorable cardiovascular
      events during 24 months of observation compared with MM genotype carriers.

PMID- 29578436
TI  - INTERRELATION OF THE GENE 4DKN1A (RS 1801270) POLYMORPHIC STATE AND LEVEL OF
      DEVELOPMENT OF CARIES IN CHILDREN WITH DOWN SYNDROME.
AB  - Study is devoted for rs1801270 polymorphism of CDKN1A gene due to the level of
      intensity of caries development in children with Down syndrome. The full
      development of oral cavity organs is ensured through a complex of genes whose
      protein products control different stages of this difficult process. Changes in
      gene structure, as well as disturbance of their expression may lead to
      abnormalities of development of teeth and periodontal tissues. Analysis of the
      polymorphism of CDKN1A gene Ser31Arg in children living in Kharkiv region has
      shown that the frequency of genotypes and alleles corresponds to the
      theoretically expected distribution by Hardy-Weinberg in the core (chi2=0.12) and
      control (chi2=1.29) groups. There is no significant differences in the frequency
      of alleles of CDKN1A gene in the group of healthy children and children with Down
      syndrome (p=0.978). There is an association of heterozygous option C/A of the
      studied marker Ser31Arg of CDKN1A gene with the level of intensity of caries
      development (by Leus) in children with Down syndrome under 10 years old.

PMID- 29578437
TI  - [CORRELATION BETWEEN HEAT PAIN THRESHOLD DEGREE AND TRPV1 RECEPTOR PROTEIN LEVEL
      OVER VARIOUS PHASES OF THE OVARIAN-MENSTRUAL CYCLE].
AB  - Numerous scientific studies demonstrating differences in pain sensitivity over
      various phases of the ovarian-menstrual cycle (OMC) in healthy women have been
      published in recent decades, but the basis for these differences is however still
      poorly understood. The aim of the current study was to assess the correlation
      between the heat pain threshold degree and the dynamics of TRPV1 (Transient
      receptor potential channeling subfamily V member1) receptor protein level, as
      well as aggression degree in healthy women in the follicular and luteal phases of
      OMC. An increased TRPV1 receptor protein level and a decreased thermal pain
      threshold were found in the luteal phase of the OMC. The study revealed a
      correlation of the progesterone level in the luteal phase with a degree of
      increase of TRPV1 level, as well as with the degree of decrease of heat pain
      threshold. The relationship between the degree of pain threshold, as well as
      TRPV1 level with follicle stimulating (FSH), luteinizing (LH) hormones and
      prolactin levels was not found. Also, there was no correlation between TRPV1 or
      heat pain threshold levels and aggression degree.

PMID- 29578438
TI  - THE MORPHOLOGICAL PICTURE OF LOCAL IMMUNE RESPONSES IN THE KIDNEYS, URETERS AND
      BLADDER OF THE FOETUSES AND NEWBORNS, WHO DEVELOPED IN CONDITIONS OF MATERNAL
      PREECLAMPSIA.
AB  - The purpose of the research consisted in revealing morphological peculiarities of
      local immune responses in the kidneys, ureters and bladder of the foetuses and
      newborns, who developed in conditions of maternal preeclampsia with different
      degrees of its severity. The research was conducted on autopsy material: the
      kidneys, ureters and bladders of mature foetuses and newborns. Four groups were
      formed in the study: group I - foetuses and newborns from mothers with
      physiological pregnancy; group II - foetuses and newborns from mothers, whose
      pregnancy was complicated with a mild degree of preeclampsia; group III -
      foetuses and newborns from mothers, whose pregnancy was complicated with a
      moderately severe degree of preeclampsia; group IV - foetuses and newborns from
      mothers, whose pregnancy was complicated with severe preeclampsia. An immune
      infiltration in the organs of the urinary system of foetuses and newborns was
      studied with help of histological, immunohistochemical and morphometric methods
      of examination. In the course of the study it was revealed that local immune
      responses in the kidneys, ureters and bladder of the foetuses and newborns passed
      with some abnormal deviations characterized by quantitative changes of SD3, SD4,
      SD8, SD20 and SD68 cells, whose degree of manifestation increased from the foetus
      to the newborn and with an aggravation of maternal preeclampsia. Mild, moderately
      severe as well as severe preeclampsia resulted in an extreme activation of the
      macrophage system, T cell and B cell immunity in the kidneys, ureters and bladder
      of foetuses and newborns that manifested itself with an increase of the absolute
      count of CD3, CD20 and CD68 cells. Mild preeclampsia caused an increase of the
      absolute count of CD8 cells and a decrease of the absolute count of CD4 cells
      with a resultant lowering of the immunoregulatory index. Moderately severe and
      severe preeclampsia caused an increase of the absolute count of CD4 cells and a
      decrease of the absolute count of CD8 cells with a corresponding elevation of the
      immunoregulatory index. In foetuses and newborns from mothers with physiological
      pregnancy as well as from mothers, whose pregnancy was complicated with
      preeclampsia having different degrees of severity, their kidneys were
      characterized by a more marked infiltration with immune cells versus their
      ureters and bladder. Thus, as a result of an excessive antigenic stimulation
      caused by maternal preeclampsia the local immune responses in the organs of the
      urinary system, which in physiological conditions fulfill exclusively protective
      functions, can become alterative and develop morphofunctional changes in the
      kidneys, ureters and bladder of foetuses and newborns.

PMID- 29578439
TI  - OCCUPATIONAL HAZARDS AS A RISK FACTOR OF ONSET AND UNFAVORABLE OUTCOME OF
      ISCHEMIC HEART DISEASE.
AB  - Objective -to identify the role of occupational hazards (OH) as a risk factor of
      onset and unfavorable outcome of coronary artery disease (CAD). Retrospective
      study included analysis of 307 case reports of CAD patients, including 59
      patients with long term history of OH exposure. Prospective study included
      observation of 244 STEMI patients during their in-patient treatment, including
      113 patients with prior exposure to OH. OH were demonstrated to contribute to the
      risk of CAD, and to be directly involved in atherosclerotic coronary artery (CA)
      injury, its role being equal to that of the classical risk factors, such as
      arterial hypertension (AH), dyslipidemia, and diabetes mellitus (DM). As shown by
      regression analysis, AH, DM, and dyslipidemia primarily promote atherogenesis in
      second and third order CA, while technogenic xenobiotics - mostly in first and
      second order CA, including the left CA truncus. History of OH directly affects
      the degree of stenosis, along with such important factors as LDL cholesterol, HDL
      cholesterol, triglycerides, and AH. According to Caplan-Meyer curves, OH exposure
      affects the hospital course of STEMI due to the adverse impact of technogenic
      xenobiotics leading, which contributes to the main mechanisms of CAD progression.
      In these patients the activity of systemic inflammation is higher, endothelial
      dysfunction, and autonomic disbalance and heterogeneity of myocardial
      repolarization are more profound. More pronounced remodeling of left ventricle,
      which is apparently due to the pre-existing abnormalities of cardiomyocytes
      caused by the long term effect of technogenic xenobiotics, significantly impairs
      the functional condition of myocardium, and accordingly the patient's prognosis.
      Our data suggest occupational hazards as a risk factor for onset and progression
      of CAD. Further studies involving this patient category are necessary.

PMID- 29578440
TI  - [PHYTOCORRECTION OF IMMUNOLOGICAL AND BIOCHEMICAL CHANGES IN THE COMBINED IMPACT
      OF COAL DUST AND HIGH DOSE OF RADIATION].
AB  - The objective of this researsh is to study the effects of Eminium Regelii
      phytopreparation (ERP) on immune status and free radical oxidation in the tissues
      of the adrenal glands and immunocompetent organs after combined exposure to 6 Gy
      dose of gamma irradiation and coal dust (remote period). The study was realized
      on 30 white laboratory male rats of the Wistar line, weighing 240+/-20g, that
      were divided into equal 3 groups: I group - intact, II group - were exposured to
      combined effects of coal dust and gamma irradiation, III group - were exposured
      to combined effects and in parallel taking phytopreparation Eminium Regel. The
      animals of II and III groups were irradiated 90 days prior to the study at the
      TERAGAM 60Co radiotherapy unit ("ISOTREND spol. S.r.o.", Czech Republic) in dose
      of 6 Gy once. Experimental animals received phytopreparation of ER 2.5 mg/kg per
      day on calculate of body mass for 14 days. The results of the conducted studies
      showed that in the long-term period after the actions of the sublethal dose of
      gamma radiation and coal dust, significant changes were revealed that were
      characterized by a decrease in immunological reactivity, increased
      lipoperoxidation and inhibition of antioxidant defense activity of the organism.
      After exposure to ER, oxidative stress was alleviated, sufficient restoration of
      antioxidant protection and immune system indices, which were disrupted by the
      combined effects of a single high dose of radiation and a prolonged three-month
      inhalation of coal dust.

PMID- 29578441
TI  - EFFECT OF TOBACCO SMOKE ON ROS PRODUCTION AND INFLAMMATION IN RATS OF DIFFERENT
      AGE.
AB  - The aim of our study was to investigate the effect of tobacco smoke on the
      content of reactive oxygen species (ROS) and level of cytokines in blood of rats
      of different age groups. For the purpose of carrying out the dosage, the beards
      of the white mongrel male rats were sub-divided into three groups: immature,
      mature and senile rats. Rat experimental groups were exposed to tobacco smoke
      daily for 45 days. The model of dependence on the chronic action of tobacco smoke
      was created using a sealed chamber in volume of 30 liters, which allowed to
      immerse animals in free behavior. Blood and blood serum was used for research.
      The isolation of neutrophils and lymphocytes from the blood was carried out by
      the method of gradient centrifugation on the double gradient of density ficol
      verografin. The ROS production level was analyzed according to the intensity of
      the fluorescence. The immune enzyme method, using test systems in the blood
      serum, determined the level of proinflammatory cytokine, interleukin 6 (IL-6) and
      anti-inflammatory - interleukin 4 (IL-4). It was found that exposure to tobacco
      smoke in rats developed oxidative stress, as evidenced by increased formation of
      ROS in neutrophils and blood lymphocytes of all the study groups of animals. In
      this case, the level of ROS depends not only on the age of the animals, but also
      on the duration of the action of tobacco smoke. In the blood serum of all age
      groups of rats, pronounced changes in IL-6 content were observed on the 45th day
      of exposure to tobacco smoke. The highest IL-6 content was observed in immature
      rats at the end of the experiment. . At the same time, the content of anti
      inflammatory cytokine IL-4 was significantly decreased in all age groups of
      animals. The results indicate an imbalance between the level of pro- and anti
      inflammatory cytokines, in particular IL-6 and IL-4. The result of exposure to
      tobacco smoke is the development of oxidative stress and inflammatory processes
      that depend on the duration of the smoke, its concentration, the age of the
      animals, and other biologically active constituents.

PMID- 29578442
TI  - DEVELOPMENT OF THE FORMULATION AND TECHNOLOGY OF HYDROGEL, CONTAINING ADJARA
      REGION SULFIDE SILT PELOID.
AB  - In the world today, the demand for the preparations and cosmetics, made of
      peloids is increasing significantly, which is explained by the increased interest
      of the community to the ecologically clean raw materials of natural origin, it
      often replaces expensive chemical preparations, which are often accompanied by
      some contraindications. The increased interest in peloids in the world put on the
      agenda the question of rational use of acting mud mines as well as the problem of
      cosmetic and medicinal preparations, developed on their basis. It is noteworthy
      that the development of ready-made, soft drug forms from the Adjara region
      sulfide silt peloids is one of the most topical and important issues, as at
      present there is not available the form of ready-made drugs containing the
      sulfide silt peloids of this region. Therefore, the aim of the research was to
      develop the formulation and technology of the hydrogel, containing the Adjara
      region sulfide silt peloid. The sulfide silt peloid of the Ardagani lake have
      been used for preparing the hydrogel compositions, as it is distinguished by its
      advantageous physical-chemical properties and content of biologically active
      ingredients compared with other studied peloids. The main physical-chemical and
      technological characteristics of hydrogels compositions have been studied using
      the following methods: uniformity, pH, the colloidal stability, thermal stability
      , osmotic activity - by dialysis method using semiconductor membrane
      (Kruvichinski method), release of active ingredient was studied by using Franz
      diffusion cells, viscosity was determined by Viscometer RVDV-1 T (Dongguan
      Zhongli Instrument Technology Co., China), the structure of hydrogel composition 
      by microscopic (ROW Rathenow, Germany) examination. Based on the conducted
      studies have been established, that the hydrogel composition N6 is distinguished
      by its best properties compared to other hydrogel compositions, in which the
      carboxymethylcellulose was used as a base.The conducted studies became the basis
      for the development of the formula and technological scheme of production for the
      hydrogel of Ardagani lake sulfide silt peloid of Adjara region. The results of
      determining the main characteristics of the given gel provide the desired quality
      and efficiency of the product.

PMID- 29578443
TI  - MICROSCOPIC FEATURES OF THE SPLEEN UNDER THE INFLUENCE OF LAPROXIDES.
AB  - Rapid technology growth and its implementation in all spheres of the people's
      lives dictates the necessity for thorough study of the influence of different
      chemicals on human's health. This study was undertaken to elucidate the
      structural changes that occur in the matured rats' spleen experimentally induced
      by selected xenobiotic, so, purpose of our work was detection of microscopic
      peculiarities of the spleen under the influence of laproxides. In subacute
      experiment were uncovered organometric alterations of the matured male rat's
      spleen after the administration of 1/10 LD50 of polyether-tryglycidyl ether of
      polyoxypropylene triol (TEPPT). The study was performed on 72 outbreed WAG male
      matured rats with the weight 200+/-10g. Histological slides were studied with
      performing morphometric and statistical methods. We revealed changes of
      morphologis data in comparison to control data which shows reactivity of the
      spleen in response to the induced xenobiotic. The received and analyzed data
      demonstrate the morphological changes of the spleen, specifically changes of the
      linear dimensions and weight of the spleen due to the influence of the TEPPT. The
      spleen is very sensitive to the effects of xenobiotics, in particular, TEPPT that
      is even reflected in its grossly (weight and linear dimensions) and histological
      features (reliable changes of the of the white pulp area of the spleen from
      17.87+/-1.04% to 27.37+/-1.71%, diameter of lymphatic follicles from 426.59+/
      11.18 MUm to 382.31+/-11.73 MUm, width of the mantle zone from 45.73+/-1.08 MUm
      to 37.18+/-2.29 MUm, width of the marginal zone from 81.32+/-1.79 MUm to 74.63+/
      2.08 MUm, width of the periarterial zone from 88.73+/-2.69 MUm to 97.24+/-2.61
      MUm).

PMID- 29578444
TI  - MORPHOLOGICAL CHARACTERISTICS OF ANGIOGENESIS IN ADENOCARCINOMA OF COLON.
AB  - The study of the process of angiogenesis and microcirculation with the help of
      modern methods of morphological research including type and maturity of the
      tumor, location and is considered a problem of special importance and value. The
      purpose of this research is to study the particularity of angiogenesis and
      microcirculation in colon adenocarcinomas. The human tissue samples of colon
      adenocarcinoma (19 cases, 40 observation sites) were studied by light
      microscopic, electron- microscopic, electron-radiographic and immunohistochemical
      methods. For electron-radiographic studies - the sections of tissue were
      incubated separately in radioactive precursor 3H - thymidine and 3H - uridine.
      For immohistochemical studies markers CD34 and VEGF-A were used. According to
      analyzed data, de novo hyperplasia of endotheliocytes was detected by positive
      reaction on VEGF-A and CD34 markers in adenocarcinoma vascular structures.
      Special interest provide the VEGF-A and CD34 expression in stromal components.
      There is also an increase DNA synthesis in adenocarcinoma. Intra-tumor
      neoangiogenesis and changes in microcirculation are one of the most important
      factors regulating the processes of proliferation of atypical cells. The data
      obtained makes it possible to judge the prognosis, metastasis, and also the
      biopotential of neoplastic progression.

PMID- 29578445
TI  - EPIDEMIOLOGY OF CLOSTRIDIUM DIFFICILE INFECTION IN HOSPITALISED PEDIATRIC
      PATIENTS IN GEORGIA.
AB  - Clostridium difficile, a Gram-positive spore-forming bacillus, is the most common
      identifiable etiologic agent of antibiotic-associated diarrhea. The incidence of
      Clostridium difficile infections among hospitalized children has been increasing
      across the world. The aim of our study was to evaluate occurrence of Clostridium
      difficile and some other gastrointestinal pathogens among hospitalized pediatric
      patients in Georgia, as far as currently statistical data on the topic is very
      limited in the country. One of the objectives of the study was to test and pilot
      the real-time Polymerase Chain Reaction diagnostic systems for rapid and
      simultaneous identification of number of pathogens with a particular emphasis on
      diarrheal disease diagnostics as these are one of the primary public health
      priorities in Georgia and worldwide. Cross-Sectional study has been performed on
      211 samples collected from 192 pediatric patients. Two pediatric hospitals were
      involved in the study: M. Iashvili Children's Central Hospital and Tbilisi
      Children's Clinical Hospital for Infectious Diseases. Laboratory investigations
      were done in the Clinic NeoLab, Tbilisi, Georgia. Study materials collected for
      testing were stool samples. Samples were tested by EIA kits (CerTest biotec,
      Zaragoza, Spain) for presence of A/B toxin according to the manufacturer's
      instructions. EIA test positive samples were analyzed by home-made multiplex real
      time polymerase chain reaction (NeoPCR Diagnostics, NeoLab, Tbilisi, Gerogia) for
      confirmation of the infection and for simultaneous identification of additional
      gastrointestinal pathogens including Entamoeba histolitica, Giardia lamblia,
      Cryptsporidium parvum, Adenovirus, Rotavirus, Norovirus and Astrovirus. All
      samples were also tested for the presence of the above listed pathogenic agents
      using the same type EIA kits as for Clostridium difficile described above
      (CerTestbiotec, Zaragoza, Spain) for presence of the corresponding pathogen. The
      average age of the study participants was 3.5 years, 56.7% were male and 43.3%
      were female patients. Presence of Clostridium difficile have been documented in
      21 samples out of 211 (10%). Besides the Clostridium difficile, other enteric
      pathogens have been revealed with the following frequencies: Rotavirus in 12
      cases (5.7%), Adenovirus in 11 (5.2%), Giardia lamblia in 10 (4.7%), Astrovirus
      in 3 (1.4%), Cryptsporidium parvum in 3 (1.4%), Entamoeba histolitica in 2
      (0.9%), Norovirus in 2 (0.9%). 49 samples were from out-patient cases (2 samples
      were positive for Clostridium difficile) and 162 samples were from in-patient
      cases (19 samples were positive for Clostridium difficile). Clostridium difficile
      is the frequent pathogenic agent causing diarrheal disease among hospitalized
      pediatric patients. Development of Clostridium difficile related diarrhea is
      associated with the antibiotic treatment of pediatric patients hospitalized due
      to different clinical diagnosis. Targeted early detection of these pathogens is
      important for the optimal management of diarrheal infection in pediatric patient
      which will lead to the better clinical outcome and reduction of morbidity rate
      among hospitalized pediatric patients.

PMID- 29578446
TI  - SELF-PERCEIVED HEALTH STATUS AND ILLNESSES AMONG INTERNALLY DISPLACED PEOPLE IN
      GEORGIA.
AB  - Georgia had several waves of internally displaced people (IDPs) as a result of
      military conflicts on the territories of Abkhazia and Samachablo starting from
      1990's with the latest large wave in 2008. Most of the IDPs live in compact
      settlements, such as old administrative buildings or specially constructed camps.
      In both cases, living conditions and social-economic status of IDPs are below
      Georgia's national average. There is extremely limited data on the health status
      of the IDPs in Georgia. Health Research Union (HRU) with support from ELRHA/R2HC
      program conducted a survey to study health service utilization and expenditures
      among IDPs, and measure the effect of targeted intervention versus untargeted,
      integrated approach to health financing. The aim of the current study was to
      analyze the self-reported health status among IDPs on the basis of the data
      collected through this survey. The survey was carried out among IDPs currently
      living in Georgia mainly residing in compact settlements. Sampling from the
      target population was performed by a multi-stage cluster sampling approach. In
      total 1.319 households with 4,359 household members were recruited and
      interviewed for the survey. Male accounted for almost 55% of all household
      members in the survey. Slightly less than half of respondents were married;
      children under the age of 15 constituted 23% of all IDPs surveyed. In total, 40%
      of all respondents (1729 persons) report being chronically ill and identify a
      wide range of conditions. Of them 532 report having 2 or more chronic diseases.
      About a third of occurrences (29%) of chronic diseases is attributed to
      cardiovascular diseases. Musculoskeletal and gastrointestinal diseases (each)
      constitute 13% of all occurrences of chronic diseases. During last 24 months 129
      household members gave birth. The prevalence of chronic diseases among adult
      population increases as the age advances with the highest rate among those aged
      above 65 with 84% reporting having at least one chronic disease. Self-perceived
      overall health status was characterized as excellent, very good and good by 53%,
      as fair by 32% and as poor and very poor by 16% of the respondents. The conducted
      research was the first wide-scale study of the health status among internally
      displaced people in Georgia. These data may contribute to better understand the
      problems in this vulnerable population and evaluate impact of the implementation
      of the different models of the health care including targeted health insurance
      for IDPs.

PMID- 29578447
TI  - Smectic viral capsids and the aneurysm instability.
AB  - The capsids of certain Archaea-infecting viruses undergo large shape changes,
      while maintaining their integrity against rupture by osmotic pressure. We propose
      that these capsids are in a smectic liquid crystalline state, with the capsid
      proteins assembling along spirals. We show that smectic capsids are intrinsically
      stabilized against the formation of localized bulges with non-zero Gauss
      curvature while still allowing for large-scale cooperative shape transformation
      that involves global changes in the Gauss curvature.

PMID- 29578448
TI  - Laser bioprinting of human induced pluripotent stem cells-the effect of printing
      and biomaterials on cell survival, pluripotency, and differentiation.
AB  - Research on human induced pluripotent stem cells (hiPSCs) is one of the fastest
      growing fields in biomedicine. Generated from patient's own somatic cells, hiPSCs
      can be differentiated towards all functional cell types and returned to the
      patient without immunological concerns. 3D printing of hiPSCs could enable the
      generation of functional organs for replacement therapies or realization of organ
      on-chip systems for individualized medicine. Printing of living cells was
      demonstrated with immortalized cell lines, primary cells, and adult stem cells
      with different printing technologies and biomaterials. However, hiPSCs are more
      sensitive to handling procedures, in particular, when dissociated into single
      cells. Both pluripotency and directed differentiation are influenced by numerous
      environmental factors including culture media, biomaterials, and cell density.
      Notably, existing literature on the effect of applied biomaterials on
      pluripotency is rather ambiguous. In this study, laser bioprinting of
      undifferentiated hiPSCs in combination with different biomaterials was performed
      and the impact on cells' behavior, pluripotency, and differentiation was
      investigated. Our findings suggest that hiPSCs are indeed more sensitive to the
      applied biomaterials, but not to laser printing itself. With appropriate
      biomaterials, such as the hyaluronic acid based solutions applied in this study,
      hiPSCs can be successfully laser printed without losing their pluripotency.

PMID- 29578449
TI  - Inkjet printable-photoactive all inorganic perovskite films with long effective
      photocarrier lifetimes.
AB  - Photoactive perovskite quantum dot films, deposited via an inkjet printer, have
      been characterized by x-ray diffraction and x-ray photoelectron spectroscopy. The
      crystal structure and bonding environment are consistent with CsPbBr3 perovskite
      quantum dots. The current-voltage (I-V) and capacitance-voltage (C-V) transport
      measurements indicate that the photo-carrier drift lifetime can exceed 1 ms for
      some printed perovskite films. This far exceeds the dark drift carrier lifetime,
      which is below 50 ns. The printed films show a photocarrier density 109 greater
      than the dark carrier density, making these printed films ideal candidates for
      application in photodetectors. The successful printing of photoactive-perovskite
      quantum dot films of CsPbBr3, indicates that the rapid prototyping of various
      perovskite inks and multilayers is realizable.

PMID- 29578450
TI  - Multiphoton excitation and high-harmonics generation in topological insulator.
AB  - Multiphoton interaction of coherent electromagnetic radiation with 2D metallic
      carriers confined on the surface of the 3D topological insulator is considered. A
      microscopic theory describing the nonlinear interaction of a strong wave and
      metallic carriers with many-body Coulomb interaction is developed. The set of
      integrodifferential equations for the interband polarization and carrier
      occupation distribution is solved numerically. Multiphoton excitation of Fermi
      Dirac sea of 2D massless carriers is considered for a THz pump wave. It is shown
      that in the moderately strong pump wave field along with multiphoton
      interband/intraband transitions the intense radiation of high harmonics takes
      place.

PMID- 29578451
TI  - Instability of the sliding Luttinger liquid.
AB  - We revise a phase diagram for the sliding Luttinger liquid (SLL) of coupled one
      dimensional quantum wires packed in two- or three-dimensional arrays in the
      absence of a magnetic field. We analyse whether physically justifiable
      (reasonable) inter-wire interactions, i.e. either the screened Coulomb or
      'Coulomb-blockade' type interactions, stabilise the SLL phase. Calculating the
      scaling dimensions of the most relevant perturbations (the inter-wire single
      particle hybridisation, charge-density wave, and superconducting inter-wire
      couplings), we find that their combination always destroys the SLL phase for the
      repulsive intra-wire interaction. However, suppressing the inter-wire tunnelling
      of repulsive fermions (when the charge-density wave is the only remaining
      perturbation), one can observe a stability region emerging due to the inter-wire
      forward scattering interaction.

PMID- 29578452
TI  - Influence of upper limb movement patterns on accelerometer measurements: a
      pediatric case series.
AB  - OBJECTIVE: Previous studies showed success using wrist-worn accelerometers to
      monitor upper-limb activity in adults and children with hemiparesis. However, a
      knowledge gap exists regarding which specific joint movements are reflected in
      accelerometry readings. We conducted a case series intended to enrich data
      interpretation by characterizing the influence of different pediatric upper-limb
      movements on accelerometry data. APPROACH: The study recruited six typically
      developing children and five children with hemiparetic cerebral palsy. The
      participants performed unilateral and bilateral activities, and their upper limb
      movements were measured with wrist-worn accelerometers and the Microsoft Kinect,
      a markerless motion-capture system that tracks skeletal data. The Kinect data
      were used to quantify specific upper limb movements through joint angle
      calculations (trunk, shoulder, elbow and wrist). Correlation coefficients (r)
      were calculated to quantify the influence of individual joint movements on
      accelerometry data. Regression analyses were performed to examine multi-joint
      patterns and explain variability across different activities and participants.
      MAIN RESULTS: Single-joint correlation results suggest that pediatric wrist-worn
      accelerometry data are not biased to particular individual joint movements.
      Rather, the accelerometry data could best be explained by the movements of the
      joints with the most functional relevance to the performed activity.
      SIGNIFICANCE: This case series provides deeper insight into the interpretation of
      wrist-worn accelerometry data, and supports the use of this tool in quantifying
      functional upper-limb movements in pediatric populations.

PMID- 29578453
TI  - Effect of pH on the hinge region of influenza viral protein: a combined constant
      pH and well-tempered molecular dynamics study.
AB  - Despite the knowledge that the influenza protein, hemagglutinin, undergoes a
      large conformational change at low pH during the process of fusion with the host
      cell, its molecular mechanism remains elusive. The present constant pH molecular
      dynamics (CpHMD) study identifies the residues responsible for large
      conformational change in acidic condition. Based on the pKa calculations, it is
      predicted that His-106 is much more responsible for the large conformational
      change than any other residues in the hinge region of hemagglutinin protein.
      Potential of mean force profile from well-tempered meta-dynamics (WT-MtD)
      simulation is also generated along the folding pathway by considering radius of
      gyration (R gyr) as a collective variable (CV). It is very clear from the present
      WT-MtD study, that the initial bending starts at that hinge region, which may
      trigger other conformational changes. Both the protein-protein and protein-water
      HB time correlation functions are monitored along the folding pathway. The
      protein-protein (full or hinge region) HB time correlation functions are always
      found to be stronger than those of the protein-water time correlation functions.
      The dynamical balance between protein-protein and protein-water HB interactions
      favors the stabilization of the folded state.

PMID- 29578454
TI  - Entanglement loss in molecular quantum-dot qubits due to interaction with the
      environment.
AB  - We study quantum entanglement loss due to environmental interaction in a
      condensed matter system with a complex geometry relevant to recent proposals for
      computing with single electrons at the nanoscale. We consider a system consisting
      of two qubits, each realized by an electron in a double quantum dot, which are
      initially in an entangled Bell state. The qubits are widely separated and each
      interacts with its own environment. The environment for each is modeled by
      surrounding double quantum dots placed at random positions with random
      orientations. We calculate the unitary evolution of the joint system and
      environment. The global state remains pure throughout. We examine the time
      dependence of the expectation value of the bipartite Clauser-Horne-Shimony-Holt
      (CHSH) and Brukner-Paunkovic-Rudolph-Vedral (BPRV) Bell operators and explore the
      emergence of correlations consistent with local realism. Though the details of
      this transition depend on the specific environmental geometry, we show how the
      results can be mapped on to a universal behavior with appropriate scaling. We
      determine the relevant disentanglement times based on realistic physical
      parameters for molecular double-dots.

PMID- 29578455
TI  - Spin Hall effect originated from fractal surface.
AB  - The spin Hall effect (SHE) has shown promising impact in the field of spintronics
      and magnonics from fundamental and practical points of view. This effect
      originates from several mechanisms of spin scatterers based on spin-orbit
      coupling (SOC) and also can be manipulated through the surface roughness. Here,
      the effect of correlated surface roughness on the SHE in metallic thin films with
      small SOC is investigated theoretically. Toward this, the self-affine fractal
      surface in the framework of the Born approximation is exploited. The surface
      roughness is described by the k-correlation model and is characterized by the
      roughness exponent H [Formula: see text], the in-plane correlation length xi and
      the rms roughness amplitude delta. It is found that the spin Hall angle in
      metallic thin film increases by two orders of magnitude when H decreases from H 
      =  1 to H  =  0. In addition, the source of SHE for surface roughness with
      Gaussian profile distribution function is found to be mainly the side jump
      scattering while that with a non-Gaussian profile suggests both of the side jump
      and skew scatterings are present. Our achievements address how details of the
      surface roughness profile can adjust the SHE in non-heavy metals.

PMID- 29578456
TI  - Spark plasma sintering of bulk SrAl2O4-Sr3Al2O6 eutectic glass with wide-band
      optical window.
AB  - SrAl2O4-Sr3Al2O6 eutectic glass was prepared by using an aerodynamic levitator
      equipped with a CO2 laser device. A bulk transparent amorphous sample was
      obtained by the spark plasma sintering (SPS) of the prepared eutectic glass. XRD,
      a UV-vis-NIR spectrophotometer and FT-IR were employed to characterize the phase
      evolution and optical properties. The results show that the bulk SrAl2O4-Sr3Al2O6
      samples fabricated by the containerless process and SPS between 852  degrees C
      857  degrees C were fully amorphous. The amorphous sample has a wide transparent
      window between 270 nm and 6.2 MUm. The average refractive index in the visible
      light region is 1.680 and the Abbe number is 27.4. The prepared bulk SrAl2O4
      Sr3Al2O6 eutectic glass with the wide-band optical window may be a promising
      candidate for optical applications.

PMID- 29578457
TI  - Corrigendum: Van der Waals interaction in uniaxial anisotropic media (2013 J.
      Phys.: Condens. Matter 25 035102).
AB  - A multiplication error led to incorrect values of C2e and C1o in Table 1 of the
      above paper. The correct table is given below. All numerical results, graphs, and
      conclusions of the paper remain unchanged. &#13.

PMID- 29578458
TI  - Anisotropic visible photoluminescence from thermally annealed few-layer black
      phosphorus.
AB  - Black phosphorus, a two-dimensional material, with high carrier mobility, tunable
      direct bandgap and anisotropic electronic properties has attracted enormous
      research interest towards potential application in electronic, optoelectronic and
      optomechanical devices. The bandgap of BP is thickness dependent, ranging from
      0.3 eV for bulk to 1.3 eV for monolayer, while lacking in the visible region, a
      widely used optical regime for practical optoelectronic applications. In this
      work, photoluminescence (PL) centered at 605 nm is observed from the thermally
      annealed BP with thickness <=20 nm. This higher energy PL is most likely the
      consequence of the formation of higher bandgap phosphorene oxides and suboxides
      on the surface BP layers as a result of the enhanced rate of oxidation. Moreover,
      the polarization-resolved PL measurements show that the emitted light is
      anisotropic when the excitation polarization is along the armchair direction.
      However, if excited along zigzag direction, the PL is nearly isotropic. Our
      findings suggest that the thermal annealing of BP can be used as a convenient
      route to fill the visible gap of the BP-based optoelectronic and optomechanical
      devices.

PMID- 29578459
TI  - The relationship between serum E2 levels and recurrence in premenopausal, ER
      positive breast cancer patients: A retrospective study.
AB  - BACKGROUND: Among estrogens, estradiol (E2) has the strongest physiological
      activity as a stimulator in estrogen receptor (ER)-positive breast cancer. The
      aim of this study is to investigate E2 dynamics during endocrine therapy and to
      explore the optimal environment in which tamoxifen (TAM) exhibits better efficacy
      for ER-positive premenopausal early breast cancer patients. METHODS: This is a
      retrospective study enrolled 194 patients with premenopausal ER-positive early
      stage breast cancer who aging <=45 years at onset and receiving luteinizing
      hormone-releasing hormone-agonist (LHRH-a) and TAM-therapy. Approximately half of
      the patients also received pre- or post-operative chemotherapy as adjuvant
      systemic therapy. We studied the relationship between recurrence and serum
      hormonal dynamics during adjuvant therapy. We monitored the concentrations of E2
      and, follicle-stimulating hormone (FSH) in the blood before, during, and after
      treatment. The median follow-up period was 80 (14-555) months. RESULTS: Forty-six
      (23.7%) patients developed recurrent breast cancer after surgery. The prognoses
      were favorable in the group receiving longer LHRH-a exposure if those patients
      did not receive chemotherapy as their adjuvant therapy. Paradoxically, patients
      with high serum E2 levels after LHRH-a showed a low recurrence ratio. This
      phenomenon might be explained by the similar mechanisms of estrogen therapy after
      estrogen depletion by aromatase inhibitor (AI) therapy for metastatic breast
      cancer. CONCLUSION: Among patients who received endocrine therapy without
      adjuvant chemotherapy, those with longer LHRH-a exposure had favorable prognoses.
      A potential association was observed between recurrence and E2 concentrations in
      women with premenopausal ER-positive early-stage breast cancer.

PMID- 29578460
TI  - Recovery time course of erythrocyte deformability following exposure to shear is
      dependent upon conditioning shear stress.
AB  - BACKGROUND: Red blood cell (RBC) deformability may increase, or decrease,
      following application of shear stress ("shear conditioning"), depending upon the
      specific magnitude and duration of exposure. However, the time course of altered
      RBC deformability following shear remains unresolved. OBJECTIVE: We utilised
      shear conditioning known to increase (10 Pa) or decrease (64 Pa) RBC
      deformability and subsequently rested the cells; serial measurements of
      deformability during the rest period facilitated defining the time course of
      recoverability. A second experiment repeated the shear conditioning and recovery
      period to explore whether multiple duty-cycles augmented the response following
      the initial exposure. METHODS: Shear conditioning was performed for 300 s at the
      desired shear stress. Ektacytometry was used to quantify human RBC deformability
      immediately and during rest (3, 5, 60, 120, 240, 300 s) using discrete samples.
      RBC were shear conditioned twice in a separate experiment, with 300 s rest
      separating the conditioning. RESULTS: Shear conditioning at 10 Pa induced
      increased cell deformability by 19.5 +/- 0.3%, which reduced to 7.2 +/- 0.4%
      after 300 s of rest. Shear conditioning at 64 Pa decreased cell deformability by
      30.5 +/- 13.9%, and after 300 s rest, remained decreased (19.3 +/- 9.4%) compared
      with baseline. The second duty-cycle augmented initial responses induced by shear
      conditioning. CONCLUSION: Specific shear conditioning results in either
      temporarily increased cell deformability, or a less reversible decrease of RBC
      deformability.

PMID- 29578461
TI  - Comparison of isometric cervical flexor and isometric cervical extensor system
      exercises on patients with neuromuscular imbalance and cervical crossed syndrome
      associated forward head posture.
AB  - BACKGROUND: Isometric cervical flexor system exercise (ICF) and isometric
      cervical extensor system exercise (ICE) are cervical stabilization techniques
      that have been used to restore cervical crossed syndrome (CCS)-associated forward
      head posture. However, the therapeutic effects and underlying motor control
      mechanisms remain elusive. PURPOSE: The purpose of present study was
      investigating the concurrent therapeutic effects of ICF and ICE on muscle size,
      muscle imbalance ratio, and muscle recruitment sequence using ultrasound imaging
      and electromyography. METHODS: A total of 18 participants (7 females; age=24+/
      4.0 years) with CCS associated with forward head posture underwent ICF and ICE.
      Paired t-test analysis was used for statistical analysis. RESULTS: Paired t-test
      analysis showed that sternocleidomastoid thickness was greater during ICF than
      ICE. Similarly, cross-sectional area and horizontal thickness of the longus colli
      were greater during ICE than ICF. The upper trapezius/lower trapezius muscle
      imbalance ratio and the pectoralis major/lower trapezius muscle imbalance ratio
      were significantly decreased during the application of ICE compared to ICF.
      CONCLUSIONS: These results provide compelling, mechanistic evidence as to how ICE
      is more beneficial for the restoration of neuromuscular imbalance than ICF in
      individuals with CCS.

PMID- 29578462
TI  - Preparation and in vitro-in vivo characterization of trans-resveratrol
      nanosuspensions.
AB  - Nanosuspensions technique is an important tool to enhance the saturation
      solubility and dissolution velocity of poorly soluble drugs. Trans-resveratrol (t
      Res) with extensive pharmacological effects was severely restricted by poor
      solubility and short biological half-life. In this study, anti-solvent
      precipitation was employed to development trans-resveratrol nanosuspensions (t
      Res NS) with PVPK30 as stabilizer. The physicochemical properties, in vitro
      release and in vivo pharmacokinetics of t-Res NS were investigated. The mean
      particle size, zeta potential, encapsulation efficiency and drug loading of t-Res
      NS prepared by the optimal prescription were 96.9 nm, -20.4mV, 78% and 28.1%,
      respectively. The morphology of t-Res nanoparticles was spherical indicated by
      SEM with amorphous phase verified by XRD and DSC. The t-Res NS present a good
      physical stability as well as enhanced chemical stability. Compared to crude
      drug, the in vitro dissolution rate of t-Res NS was increased with fitting
      Higuchi equation (Q=0.3215t1/2+0.0070). The in vivo pharmacokinetic test in rats
      showed that the AUC0~t of t-Res NS (559.4 MUg/mL.min) was about 3.6-fold higher
      than that of t-Res solution. Meanwhile, the MRT of t-Res nanosuspensions was
      longer than that of t-Res solution. These results suggested that NS may be a
      potentially nanocarrier for clinical delivery of t-Res.

PMID- 29578463
TI  - Pectin-honey hydrogel: Characterization, antimicrobial activity and
      biocompatibility.
AB  - BACKGROUND: Novel pectin-honey hydrogels have been developed and characterized as
      medical device. Ideally, a wound dressing should maintain optimal fluid affinity,
      permit moisture evaporation, protect the wound from microbes, and have shape
      conformability, biocompatibility, and antibacterial activity. OBJECTIVE: A novel,
      simple and fast method to produce pectin-honey wound dressings is described.
      METHODS: The properties of these pectin-honey hydrogels were investigated,
      including swelling ability, water vapour transmission rate, hydrogen peroxide
      production, methylglyoxal content and antibacterial activity. Biocompatibility
      was assessed by proliferation assays using cultured fibroblast cells and by in
      vivo study with subcutaneous and intraperitoneal implantation in rats. RESULTS:
      Hydrogel showed a good water vapour transmission rate, fluid uptake and were not
      cytotoxic for fibroblasts. The hydrogel demonstrated good antibacterial activity
      toward clinically relevant pathogens, including S. aureus and E. coli.
      Biocompatibility was confirmed by the measurement of plasma levels of interleukin
      (IL)1 beta, IL-6, tumour necrosis factor (TNF) alpha, and prostaglandin (PG)E2.
      No histological changes were observed. CONCLUSIONS: The presence of a natural
      active component, conformability, and complete resorbability are the main
      characteristics of this new biocompatible biomaterial that is well tolerated by
      the body, possibly improves healing, may be used for surgical complications
      prevention, with a simple and inexpensive production process.

PMID- 29578464
TI  - Biological and nano-indentation properties of polybenzoxazine-based composites
      reinforced with zirconia particles as a novel biomaterial.
AB  - INTRODUCTION: The biological and mechanical properties of substances are relevant
      to their application as biomaterials and there are many efforts to enhance
      biocompatibility and mechanical properties of bio-medical materials. OBJECTIVES:
      In this study, to achieve a low rate of shrinkage during polymerization, good
      mechanical properties, and excellent biocompatibility, benzoxazine based
      composites were synthesized. METHODS: Benzoxazine monomer was synthesized using a
      solventless method. FTIR and DSC analysis were carried out to determine the
      appropriate polymerization temperature. The low viscosity of the benzoxazine
      monomer at 70 degrees C attract us to use in situ polymerization after high speed
      ball milling of the benzoxazine and it mixture with different weight fractions of
      zirconia particles. Dispersion and adhesion between the ceramic and polymer
      components were evaluate by SEM. To evaluate the biological properties and
      toxicity of the polybenzoxazine-based composite samples reinforced with zirconia
      particles, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay was
      conducted. The micromechanical properties of each composite were evaluated by
      more than 20 nanoindentation tests and 3 nanoscratching tests. Surface topography
      of scratched regions was investigated using Atomic Force Microscopy. Shrinkage
      was simulated by Materials Studio software. RESULTS: SEM images showed good
      dispersion and adhesion between the ceramic and polymer components.
      Biocompatibility assay showed excellent in vitro biocompatibility. Nano
      indentation force-displacement curves showed matrix, reinforcement and interphase
      regions in specimens and excellent homogeneity in mechanical properties. The
      nanoindentation results showed that the addition of zirconia particles to the
      polybenzoxazine matrix increased the modulus and hardness of the neat
      polybenzoxazine; however, by adding more than an optimum level of reinforcement
      particles, the mechanical properties decreased due to the agglomeration of
      reinforcement particles and weak interphase that cause inappropriate load
      transferring between matrix and reinforcement particles. Results of nano
      scratching tests showed effects of zirconia particles as reinforcement on the
      coeffiecient of friction of the synthesized composites. Shrinkage simulation
      showed a low rate of shrinkage for polybenzoxazine in comparison with other low
      shrinkage polymers, such as Bis-GMA. CONCLUSION: Polybenzoxazine based composites
      that reinforced with an optimum amount of zirconia particles (60% wt micro and
      10% wt nano-particles) could be used as a novel biomaterial duo to its excellent
      biocompatibility, good mechanical properties, appropriate viscosity and low rate
      of polymeization shrinkage.

PMID- 29578465
TI  - Fluid-structure interaction of patient-specific Circle of Willis with aneurysm:
      Investigation of hemodynamic parameters.
AB  - BACKGROUND: Circle of Willis (COW) is a network of cerebral artery which
      continually supplies the brain with blood. Any disturbance in this supply will
      result in trauma or even death. One of these damages is known as brain Aneurysm.
      Clinical methods for diagnosing aneurysm can only measure blood velocity; while,
      in order to understand the causes of these occurrences it is necessary to have
      information about the amount of pressure and wall shear stress, which is possible
      through computational models. OBJECTIVE: In this study purpose is achieving exact
      information of hemodynamic blood flow in COW with an aneurysm and investigation
      of effective factors on growth and rupture of aneurysm. METHODS: Here, realistic
      three-dimensional models have been produced from angiography images. Considering
      fluid-structure interaction have been simulated by the ANSYS.CFX software.
      RESULTS: Hemodynamic Studying of the COW and intra-aneurysm showed that the WSS
      and wall tension in the neck of aneurysms for case A are 129.5 Pa, and 12.2 kPa
      and for case B they are 53.3 Pa and 56.2 kPa, and more than their fundus, thus
      neck of aneurysm is prone to rupture. CONCLUSION: This study showed that the
      distribution of parameters was dependent on the geometry of the COW, and maximum
      values are seen in areas prone to aneurysm formation.

PMID- 29578467
TI  - The influence of curvature wall on the blood flow in stenosed artery: A
      computational study.
AB  - The current study investigates the curvature effect due to various angles of
      curvature on the blood flow in human artery. The stenosis is considered to have
      three sizes 70%, 80% and 90% blockage before the curve section of artery.
      Numerical study of four different angle of curvature was considered to understand
      the flow behavior of artery having various curvatures, on the hemodynamics
      factors that includes drop in arterial pressure, flow velocity as well as wall
      shear stress. It was found that, the augmentation of the flow resistance due to
      the curvature increases in presence of stenosis. It was also noted that the wall
      shear is higher at the outer wall as compared to the inside wall in four models
      considered. Results showed that both the curvature of artery and size of the
      stenosis have significant impact. These two factors should be considered by
      cardiologist to assess the complexity of stenosis.

PMID- 29578466
TI  - Collagen and mPCL-TCP scaffolds induced differential bone regeneration in ovary
      intact and ovariectomized rats.
AB  - BACKGROUND: The data on biomaterial-mediated bone regeneration directly comparing
      commercially available scaffolds in aging and osteoporotic conditions remain
      sparse. OBJECTIVE: To investigate the effects of an absorbable collagen sponge
      (ACS) and a medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP)
      scaffold on calvarial defect healing in ovary-intact and ovariectomized rats.
      METHODS: Forty-two, 5-month old female Sprague-Dawley rats were divided into sham
      (OVI) or ovariectomy (OVX) groups (n=21). When rats reached 6 months old, 7 mm
      diameter calvarial defects were created and treated, further dividing each group
      into blood clot control, mPCL-TCP, or ACS subgroups (n=7). After four weeks, the
      calvarial specimens were evaluated using micro-computed tomography for bone
      volume fraction (BVF), and histopathology. RESULTS: The effects of ovariectomy
      were confirmed by changes in body, uterine, and vaginal weight, and osteopenia in
      the femur. A significant increase in BVF was observed in ACS-subgroups compared
      with their respective control groups (p<0.05). Histopathological analysis
      revealed no cellular inflammatory infiltrate in any group. Fibrous tissue
      encapsulated the mPCL-TCP, while the ACS was well-integrated with the bone
      matrix. The OVX groups presented more osteoid and enlarged marrow cavities
      compared with the OVI groups. CONCLUSION: ACS scaffold enhanced calvarial bone
      regeneration in OVI and OVX rats after four weeks.

PMID- 29578468
TI  - Strategy on biological evaluation for biodegradable/absorbable materials and
      medical devices.
AB  - During the last two decades, biodegradable/absorbable materials which have many
      benefits over conventional implants are being sought in clinical practices.
      However, to date, it still remains obscure for us to perform full physic-chemical
      characterization and biological risk assessment for these materials and related
      devices due to their complex design and coherent processing. In this review,
      based on the art of knowledge for biodegradable/absorbable materials and
      biological risk assessment, we demonstrated some promising strategies to
      establish and improve the current biological evaluation systems for these
      biodegradable/absorbable materials and related medical devices.

PMID- 29578469
TI  - An alternative solvent for electrospinning of fibrinogen nanofibers.
AB  - Fibrinogen plays a necessary role in blood clotting and wound healing. In this
      study, a new solvent mixture of formic acid/acetic acid with low toxicity was
      investigated as an alternative solvent for fibrinogen electrospinning. The
      nanofibers were analyzed by scanning electron microscope (SEM), simultaneous
      thermal analysis (STA) and attenuated total reflectance-Fourier transform
      infrared spectroscopy (ATR-FTIR). The results showed that when the ratio of
      formic acid to acetic acid was 75/25 (v/v) the finest defect-free fibres with
      diameters ranging from 184 +/- 37 to 241 +/- 70 nm were obtained. In addition,
      the average fibre diameters increase with increasing concentration of fibrinogen
      from 10wt% to 12wt%. It is concluded that solvent mixture consisting of formic
      acid/acetic acid can be a great solvent for electrospinning of fibrinogen and is
      able to produce nanofiber structures.

PMID- 29578470
TI  - Development of asymmetric stent for treatment of eccentric plaque.
AB  - The selection of stent and balloon type is decisive in the stenting process. In
      the treatment of an eccentric plaque obstruction, a symmetric expansion from
      stent dilatation generates nonuniform stress distribution, which may aggravate
      fibrous cap prone to rupture. This paper developed a new stent design to treat
      eccentric plaque using structural transient dynamic analysis in ANSYS. A non
      symmetric structural geometry of stent is generated to obtain reasonable stress
      distribution safe for the arterial layer surrounding the stent. To derive the
      novel structural geometry, a Sinusoidal stent type is modified by varying struts
      length and width, adding bridges, and varying curvature width of struts. An end
      ring of stent struts was also modified to eliminate dogboning phenomenon and to
      reduce the Ectropion angle. Two balloon types were used to deploy the stent, an
      ordinary cylindrical and offset balloon. Positive modification results were used
      to construct the final non-symmetric stent design, called an Asymmetric stent.
      Analyses of the deformation characteristics, changes in surface roughness and
      induced stresses within intact arterial layer were subsequently examined.
      Interaction between the stent and vessel wall was implemented by means of changes
      in surface roughness and stress distribution analyses. The Palmaz and the
      Sinusoidal stent were used for a comparative study. This study indicated that the
      Asymmetric stent types reduced the central radial recoiling and the dogboning
      phenomenon. In terms of changes in surface roughness and induced stresses, the
      Asymmetric stent has a comparable effect with that of the Sinusoidal stent. In
      addition, it could enhance the distribution of surface roughening as expanded by
      an offset balloon.

PMID- 29578471
TI  - Kinect-based virtual rehabilitation and evaluation system for upper limb
      disorders: A case study.
AB  - OBJECTIVE: To help patients with disabilities of the arm and shoulder recover the
      accuracy and stability of movements, a novel and simple virtual rehabilitation
      and evaluation system called the Kine-VRES system was developed using Microsoft
      Kinect. METHODS: First, several movements and virtual tasks were designed to
      increase the coordination, control and speed of the arm movements. The movements
      of the patients were then captured using the Kinect sensor, and kinematics-based
      interaction and real-time feedback were integrated into the system to enhance the
      motivation and self-confidence of the patient. Finally, a quantitative evaluation
      method of upper limb movements was provided using the recorded kinematics during
      hand-to-hand movement. RESULTS: A preliminary study of this rehabilitation system
      indicates that the shoulder movements of two participants with ataxia became
      smoother after three weeks of training (one hour per day). CONCLUSION: This case
      study demonstrated the effectiveness of the designed system, which could be
      promising for the rehabilitation of patients with upper limb disorders.

PMID- 29578472
TI  - Bioinformatics analysis of novel transcription factors and related differentially
      regulated modules in non-union skeletal fractures.
AB  - OBJECTIVE: This study aimed to further clarify the underlying pathomechanism of
      non-union skeletal fractures. METHODS: Gene expression profile dataset GSE494
      obtained from six non-union skeletal fracture and six normal samples was
      downloaded from the Gene Expression Omnibus database. Overlapping genes in at
      least two platforms were analyzed, and differentially expressed genes (DEGs)
      between normal and disease groups were screened. Transcriptional regulatory
      relationships and differentially regulated modules of various transcription
      factors (TFs) were determined. Differentially regulated modules with unknown
      functions were subjected to functional enrichment analysis. RESULTS: Overall,
      4,252 overlapping genes in at least two platforms and 77 DEGs, including 31 up
      and 46 downregulated genes, were obtained. Overall, 64,623 transcriptional
      regulatory relationships, including 49 TFs and 3,900 target genes, and 9
      significant modules for differential regulation were identified. Three modules
      with unknown functions regulated by TFs, including zinc finger, ZZ-type
      containing 3 (ZZZ3), nuclear TF Y, alpha (NFYA), and POU class 2 homeobox 2
      (POU2F2), were identified. Enriched GO-BP terms of NFYA and POU2F2 modules
      included cell adhesion and related terms and those of ZZ3 included cell cycle,
      cell proliferation, and associated terms. CONCLUSION: Three TFs, including ZZZ3,
      POU2F2, and NFYA, and their regulated modules may have important effects on non
      union skeletal fractures. Cell proliferation may be related with ZZZ3; cell
      adhesion and its similar process may be related with POU2F2 and NFYA.

PMID- 29578473
TI  - Medial collateral ligament bursitis in a patient with knee osteoarthritis.
AB  - BACKGROUND: Medial collateral ligament (MCL) bursitis has been described as a
      distended and inflamed bursa between the superficial and deep portions of the
      MCL. It is a rare but important cause of medial knee pain. CASE DESCRIPTION: A 65
      year-old woman with knee osteoarthritis (OA) presented with severe pain and
      swelling in her left knee. She did not have a traumatic injury. After a clinical
      examination, a slight decrease in the range of motion of the left knee, and a
      painful swelling and tenderness over the medial side of the knee and proximal
      tibia were detected. The pain was exacerbated by valgus stress test. The magnetic
      resonance (MR) imaging showed a distended bursa with internal septations beneath
      the superficial portion of the MCL. MCL bursitis was considered as diagnosis and
      an ultrasound-guided corticosteroid injection into the bursa was performed.
      RESULTS: There was a significant improvement in pain intensity in the follow-up
      examination. A repeated MR imaging 2 months later showed a marked improvement,
      and approximation of the deep and superficial portions of the MCL. CONCLUSIONS:
      MCL bursitis, which is a rare condition, must be considered for the differential
      diagnosis of increased medial knee pain in patients with knee OA. Corticosteroid
      injection is an effective and safe treatment modality for the management.

PMID- 29578474
TI  - Relationship of hematologic markers with IL-17 and IL-1 beta in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: In this study, we aimed to investigate the relationship of NLR
      (Neutrophil lymphocyte ratio), MPV (mean platelet volume), PDW (distribution
      width) rates in rheumatoid arthritis (RA) patients with IL-17 and IL-1 beta which
      are within the cytokines playing an important role in etiopathogenesis and
      activity of the disease. PATIENTS AND METHODS: Fifty-seven RA patients diagnosed
      according to RA classification criteria of ACR/EULAR 2010 and 37 controls were
      included into the study. WBC (white blood cell), NEU (neutrophil), PLT
      (platelet), LYM (lymphocyte) values in complete blood count received from routine
      blood examination of patients were recorded, and NLR, PLR (platelet lymphocyte
      ratio) rates were recorded. IL-17 and IL-1 beta were studies in serum samples.
      Disease activity of RA patients was evaluated with Disease Activity Score
      (DAS28). Age, gender, disease age, BMI (body mass index), medications used, co
      morbid diseases, smoking of the patients were recorded. RESULTS: Fifty-seven RA
      patients (46 (80.7%) females, 11 (19.3%) males), and 34 patients (24 (70.6%
      females and 10 (29.4) males) as a control group were involved. Demographic
      characteristics were similar between two groups, and statistically significant
      difference was not detected between patient and control groups in terms of
      gender, age, and BMI (p> 0.05). We found higher NLR, MPV, PDW, IL-17 values in RA
      patients compared to control group (p< 0.05). There was a positive correlation of
      NLR with DAS28, CRP. While erythrocyte sedimentation rate (ESR) had negative
      correlation with MPV and PDW, it had positive correlation with PLT. We found
      positive correlation of C-reactive protein (CRP) with NLR and PLT. We could not
      find correlation of IL-1 beta and IL-17 with hematologic markers. CONCLUSION: In
      this study, we investigated the relationship of IL-17 and IL-1 beta which play an
      important role in pathogenesis of RA patients with the parameters analyzed in
      routine complete blood count, providing information about disease activity such
      as DAS 28, CRP, and ESR. We illuminated on an issue which has not discussed
      before by looking from a different angle. More extensive, follow-up studies are
      needed to emphasize the importance of these parameters and to reveal the
      relationship between cytokines during the follow-up of the disease activity.

PMID- 29578475
TI  - Recovery from nonspecific neck pain in office workers.
AB  - BACKGROUND: Neck pain has an episodic course with varying time for recovery and
      identification of individuals likely to recover is important. OBJECTIVE: The aim
      of this study was twofold: 1a) to explore the duration of recovery from
      nonspecific neck pain, and 1b) to investigate the relation between recovery
      duration and age, and 2) to evaluate whether the NHBOW can predict duration of
      recovery from non-specific neck pain. METHODS: One hundred and three from 342
      office workers reported non-specific neck pain, with information collected on
      pain intensity and disability every month for 12 months. The time to recovery was
      measured from the onset of neck pain to full recovery. The 103 office workers
      were divided into two groups using the NHBOW score. Kaplan-Meier survival curves
      were used to describe the median time to recovery. The survival curves of the two
      NHBOW groups were compared using Cox regression analysis. RESULTS: The median
      time to recovery from neck pain was 2 months. The duration of recovery was not
      significantly related with age of participants. There was no significant
      difference in time to recovery from neck pain between the NHBOW low-score group
      and the high-score group. CONCLUSION: This study showed that the NHBOW was unable
      to predict duration of recovery from nonspecific neck pain in office workers.

PMID- 29578476
TI  - Urinary incontinence due to lumbar spinal stenosis causing disability and
      lowering quality of life.
AB  - OBJECTIVES: Lumbar spinal stenosis may lead to urinary inconsistence and can have
      a negative impact on the quality of life. The aim of the study was to assess the
      incidence of urinary incontinence and quality of life in female patients with
      spinal canal stenosis comparing to control group. METHODS: The study population
      consisted of 50 women diagnosed with severe lumbar spinal canal stenosis. Their
      mean age was 55.32 +/- 12.97 years. The clinical control group consisted of 30
      women who did not suffer from any spine disorders. Their mean age was 54.87 +/-
      12.01 years. There was no difference between both groups regarding age, weight,
      BMI and number of parity. The women diagnosed with clinical and radiographic
      symptoms of spinal canal stenosis filled out an anonymous questionnaire, ODI,
      ICIQ-UI-SF, and ICIQ-LUTSqol questionnaires. RESULTS: We found urinary
      incontinence in 56% of women with lumbar spinal canal stenosis and in 43% of
      clinical control group. We also found a statistically significant correlation
      between duration of lumbar stenotic symptoms, the SLR sign, number of deliveries
      and the intensity of urinary incontinence. CONCLUSIONS: Urinary incontinence in
      women with lumbar spinal canal stenosis is significantly different from the
      control group. Leakage of urine happened more frequently, the amount of urine
      leaked was greater, and the general impact on everyday life is harsher, as
      compared to the clinical control group.

PMID- 29578477
TI  - Morpho-functional implications of myofascial stretching applied to muscle chains:
      A case study.
AB  - BACKGROUND: Most lesions of the soft tissues, especially those at the muscle
      level, are due to the lack of elasticity of the connective tissue and fascia.
      Stretching is one of the most commonly used methods of treatment for such
      musculoskeletal issues. OBJECTIVE: This study tracks the effects of stretching on
      the electromyographic activity of muscle chains, applied to a 24-year-old athlete
      diagnosed with the Haglund's disease. METHOD: For the evaluation, we used visual
      examination and surface electromyography (maximum volumetric isometric
      contraction). The therapeutic intervention consisted in the application of the
      static stretching positions, which intended the elongation of the shortened
      muscle chains. The treatment program had a duration of 2 months, with a frequency
      of 2 sessions per week and an average duration of 60 minutes. RESULTS: The
      posterior muscle chains recorded an increase in the EMG activity, while the
      anterior muscle chains tended to diminish their EMG activity. As a result of the
      applied treatment, all the evaluated muscle chains recorded a rebalancing of the
      electromyographic activity, demonstrating the efficiency of stretching as a
      method of global treatment of muscle chains. CONCLUSIONS: By analysing all the
      data, we have come to the conclusion that static stretching is an effective
      treatment method for shortened muscle chains.

PMID- 29578478
TI  - Screening of scoliosis in school children in Tehran: The prevalence rate of
      idiopathic scoliosis.
AB  - BACKGROUND: Scoliosis is the abnormal sideways curve of the spine. Screening for
      scoliosis is controversial, and there has been significant heterogeneity between
      studies. In Iran, there is still no suitable device to screen sideways curves in
      spine. OBJECTIVE: To investigate the simple scolioscreen software for screening
      the students of elementary schools for detecting schoolchildren scoliosis. This
      students has been examined by trained medical student and data entered in
      scolioscreen application of an iPhone. METHODS: One hundred forty-four 7-12 years
      old students from primary schools in the 17th district of Tehran were randomly
      invited to participate. Initial screening of the students was done in schools by
      health care provider or medical student who has been trained by a pediatrician to
      undergo a vertebral examination. Scoliometer for iPhone's smartphone has been
      used for measuring the angle of deviation. RESULTS: 1.4% of students had overt
      scoliosis and 10.4% were suspected to have a kind of mild abnormality in spine
      curve. These individuals were referred to clinic for radiologic evaluation and it
      was confirmed that relative frequency of this abnormality was defined as 4.86% in
      our population study. There was no significant correlation between sex and degree
      of spinal curve. CONCLUSIONS: Regarding the high rate of scoliosis in our
      population and approval of this screening test in different studies, routine use
      of this screening method is highly recommended in schoolchildren. It is cost
      beneficial and can be effective in prevention and early treatment of scoliosis.

PMID- 29578479
TI  - Comprehensive Characterization of the Pyroglutamate Amyloid-beta Induced Motor
      Neurodegenerative Phenotype of TBA2.1 Mice.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder and is
      being intensively investigated using a broad variety of animal models. Many of
      these models express mutant versions of human amyloid-beta protein precursor
      (AbetaPP) that are associated with amyloid-beta protein (Abeta)-induced early
      onset familial AD. Most of these models, however, do not develop bold
      neurodegenerative pathology and the respective phenotypes. Nevertheless, this may
      well be essential for their suitability to identify therapeutically active
      compounds that have the potential for a curative or at least disease-modifying
      therapy in humans. In this study, the new transgenic mouse model TBA2.1 was
      explored in detail to increase knowledge about the neurodegenerative process
      induced by the presence of pyroglutamate modified human Abeta3-42 (pEAbeta3-42).
      Analysis of the sensorimotor phenotype, motor coordination, Abeta pathology,
      neurodegeneration, and gliosis revealed formation and progression of severe
      pathology and phenotypes including massive neuronal loss in homozygous TBA2.1
      mice within a few months. In contrast, the start of a slight phenotype was
      observed only after 21 months in heterozygous mice. These data highlight the role
      of pEAbeta3-42 in the disease development and progression of AD. Based on the
      findings of this study, homozygous TBA2.1 mice can be utilized to gain deeper
      understanding in the underlying mechanisms of pEAbeta3-42 and might be suitable
      as an animal model for treatment studies targeting toxic Abeta species,
      complementary to the well described transgenic AbetaPP mouse models.

PMID- 29578481
TI  - Deficits in Regional Cerebral Blood Flow on Brain SPECT Predict Treatment
      Resistant Depression.
AB  - BACKGROUND: Depression remains an important risk factor for Alzheimer's disease,
      yet few neuroimaging biomarkers are available to identify treatment response in
      depression. OBJECTIVE: To analyze and compare functional perfusion neuroimaging
      in persons with treatment resistant depression (TRD) compared to those
      experiencing full remission. METHODS: A total of 951 subjects from a community
      psychiatry cohort were scanned with perfusion single photon emission computed
      tomography (SPECT) of the brain in both resting and task related settings. Of
      these, 78% experienced either full remission (n = 506) or partial remission (n =
      237) and 11% were minimally responsive (n = 103) or non-responsive (11%. n =
      106). Severity of depression symptoms were used to define these groups with
      changes in the Beck Depression Inventory prior to and following treatment. Voxel
      based analyses of brain SPECT images from full remission compared to the
      worsening group was conducted with the statistical parametric mapping software,
      version 8 (SPM 8). Multiple comparisons were accounted for with a false discovery
      rate (p < 0.001). RESULTS: Persons with depression that worsened following
      treatment had reduced cerebral perfusion compared to full remission in the
      multiple regions including the bilateral frontal lobes, right hippocampus, left
      precuneus, and cerebellar vermis. Such differences were observed on both resting
      and concentration SPECT scans. CONCLUSION: Our findings identify imaging-based
      biomarkers in persons with depression related to treatment response. These
      findings have implications in understanding both depression to prognosis and its
      role as a risk factor for dementia.

PMID- 29578480
TI  - Preserved Structural Network Organization Mediates Pathology Spread in
      Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.
AB  - Models of Alzheimer's disease (AD) hypothesize stereotyped progression via white
      matter (WM) fiber connections, most likely via trans-synaptic transmission of
      toxic proteins along neuronal pathways. An important question in the field is
      whether and how organization of fiber pathways is affected by disease. It remains
      unknown whether fibers act as conduits of degenerative pathologies, or if they
      also degenerate with the gray matter network. This work uses graph theoretic
      modeling in a longitudinal design to investigate the impact of WM network
      organization on AD pathology spread. We hypothesize if altered WM network
      organization mediates disease progression, then a previously published network
      diffusion model will yield higher prediction accuracy using subject-specific
      connectomes in place of a healthy template connectome. Neuroimaging data in 124
      subjects from ADNI were assessed. Graph topology metrics show preserved network
      organization in patients compared to controls. Using a published diffusion model,
      we further probe the effect of network alterations on degeneration spread in AD.
      We show that choice of connectome does not significantly impact the model's
      predictive ability. These results suggest that, despite measurable changes in
      integrity of specific fiber tracts, WM network organization in AD is preserved.
      Further, there is no difference in the mediation of putative pathology spread
      between healthy and AD-impaired networks. This conclusion is somewhat at variance
      with previous results, which report global topological disturbances in AD. Our
      data indicates the combined effect of edge thresholding, binarization, and
      inclusion of subcortical regions to network graphs may be responsible for
      previously reported effects.

PMID- 29578482
TI  - Olfactory Function is Associated with Cognitive Performance: Results of the Heinz
      Nixdorf Recall Study.
AB  - BACKGROUND: There is strong evidence for an association of olfactory dysfunction
      and neurodegenerative diseases. Studies on the association of olfaction and
      cognition in the general population are rare. OBJECTIVE: To evaluate gender- and
      age-specific associations of olfactory function and cognitive performance in a
      well characterized population-based study sample. METHODS: At the third
      examination of the Heinz Nixdorf Recall study (n = 3,087), 2,640 participants
      (48% men; 68.2+/-7.2 years) underwent Sniffin' Sticks Screening Test measuring
      olfactory function on a scale of 0-12 points. Olfactory function was rated as
      anosmic, hyposmic, or normosmic (<=6, 7-10 or >=11 points, respectively). All
      participants performed eight validated cognitive subtests. Age- (55-64 years, 65
      74 years, 75-86 years) and gender-stratified multivariate analysis of covariance
      was used to evaluate group differences in cognitive performance. RESULTS: Women
      showed better olfactory function than men (p < 0.001). For middle-aged
      participants, olfactory groups differed in almost all cognitive subtests. The
      analyses revealed no gender effects, although associations were slightly greater
      for women than for men. Anosmics showed the worst cognitive performance and
      normosmics showed the best cognitive performance. In the young- and old-aged
      groups, a quantitative association was found for anosmics in all subtests and for
      normosmics and hyposmics in almost all subtests. CONCLUSION: This is the first
      study reporting on age-specific associations of olfactory function and cognitive
      performance in the general population. The association found in middle-aged
      participants (65-74 years) may serve as a marker to improve identification of
      persons at high risk for cognitive decline and dementia.

PMID- 29578483
TI  - Polypharmacy and Potentially Inappropriate Medication in People with Dementia: A
      Nationwide Study.
AB  - BACKGROUND: Polypharmacy (use of >=5 different medications) and potentially
      inappropriate medication (PIM) are well-known risk factors for numerous negative
      health outcomes. However, the use of polypharmacy and PIM in people with dementia
      is not well-described. OBJECTIVE: To examine the prevalence of polypharmacy and
      PIM in older people with and without dementia in a nationwide population.
      METHODS: Cross-sectional study of the Danish population aged >=65 in 2014 (n =
      1,032,120) based on register data, including information on diagnoses and
      dispensed prescriptions. Polypharmacy and PIM use among people with (n = 35,476)
      and without dementia (n = 994,231) were compared, stratified by living situation
      and adjusted for age, sex, and comorbidity. The red-yellow-green list from the
      Danish Institute for Rational Pharmacotherapy and the German PRISCUS list were
      used to define PIM. RESULTS: People with dementia were more frequently exposed to
      polypharmacy (dementia: 62.6% versus no-dementia: 35.1%, p < 0.001) and likewise
      PIM (red-yellow-green: 45.0% versus 29.7%, p < 0.001; PRISCUS: 24.4% versus
      13.2%, p < 0.001). After adjustments for age, sex, and comorbidity, the
      likelihood of polypharmacy and PIM was higher for community-dwelling people with
      dementia than without dementia (odds ratio (OR); [95% confidence interval (CI)]
      polypharmacy: 1.50 [1.45-1.55]; red-yellow-green: 1.27 [1.23-1.31]; PRISCUS: 1.25
      [1.20-1.30]). In contrast, dementia slightly decreased the odds of polypharmacy
      and PIM in nursing home residents. CONCLUSION: Use of polypharmacy and PIM were
      widespread in the older population and more so in people with dementia. This
      could have negative implications for patient-safety and demonstrates the need for
      interventions to improve drug therapy in people with dementia.

PMID- 29578484
TI  - HSV-1-Specific IgG Subclasses Distribution and Serum Neutralizing Activity in
      Alzheimer's Disease and in Mild Cognitive Impairment.
AB  - Human Herpes Simplex Virus type 1 (HSV-1) infection is suggested to play a role
      in the development of Alzheimer's disease (AD). Immunoglobulin G (IgG) neutralize
      HSV-1 activity, but the virus can evade IgG-mediated immune responses by
      expressing receptor that efficiently binds the Fc portion of all IgG subclasses
      with the exception of IgG3. We analyzed HSV-1-specific IgG subclasses and IgG
      mediated serum neutralization activity against HSV-1 in individuals with a
      diagnosis of either AD or mild cognitive impairment (MCI), comparing the results
      with those obtained in age-matched healthy controls (HC). 186 individuals were
      enrolled in the study: 67 AD, 58 MCI, and 61 HC. HSV-1 IgG titers and subclasses,
      neutralizing antibody (NAb) titers, and complement C3 concentration-critical
      component of antibody-mediated effector activity-were measured in sera by ELISA;
      IgG neutralizing activity was performed on HSV-1 infected Vero cells. Results
      showed that, whereas HSV-1-specific IgG1, IgG2, and IgG4 titers as well as
      complement C3 serum concentration were comparable in all groups of individuals,
      IgG3 were more frequently detected in MCI (89%) compared to AD (75%; p < 0.05)
      and HC (68%; p = 0.003), whereas the titer is similar among the three groups (AD:
      0.66+/-0.21 OD; MCI: 0.68+/-0.24 OD; HC: 0.72+/-0.28 OD). Notably, HSV-1 specific
      neutralizing ability of AD sera was reduced even in the presence of high quantity
      of IgG3. As IgG3 plays a key role in counteracting the ability of HSV-1 to evade
      immune responses, these data reinforce the hypothesis of a pathogenetic role of
      HSV-1 in AD.

PMID- 29578485
TI  - Cysteine-Rich Repeat Domains 2 and 4 are Amyloid-beta Binding Domains of
      Neurotrophin Receptor p75NTR and Potential Targets to Block Amyloid-beta
      Neurotoxicity.
AB  - The p75 neurotrophin receptor (p75NTR) is an amyloid-beta (Abeta) receptor that
      both mediates Abeta neurotoxicity and regulates Abeta production and deposition,
      thus playing an important role in the pathogenesis of Alzheimer's disease (AD).
      The extracellular domain of p75NTR (p75ECD), consisting of four cysteine-rich
      repeat domains (CRDs), was recently reported to be an endogenous anti-Abeta
      scavenger to block p75NTR-mediated neuronal death and neurite degeneration
      signaling of Abeta and pro-neurotrophins. Identification of the specific Abeta
      binding domains of p75NTR is crucial for illuminating their interactions and the
      etiology of AD. CRDs of p75ECD were obtained by expression of recombinant
      plasmids or direct synthesis. Abeta aggregation inhibiting test and
      immunoprecipitation assay were applied to locate the specific binding domains of
      Abeta to p75ECD. The Abeta neurotoxicity antagonistic effects of different CRDs
      were examined by cytotoxicity experiments including neurite outgrowth assay,
      propidium iodide (PI) staining, and MTT assay. In the Abeta aggregation
      inhibiting test, the fluorescence intensity in the CRD2 and CRD4 treatment groups
      was significantly lower than that in the CRD1 and CRD3 treatment groups.
      Immunoprecipitation assay and western blot confirmed that Abeta could bind to
      CRD2 and CRD4. Besides, CRD2 and CRD4 antagonized Abeta neurotoxicity suggested
      by longer neurite length, less PI labelled cells, and higher cell viability than
      the control group. Our results indicate that CRD2 and CRD4 are Abeta binding
      domains of p75NTR and capable of antagonizing Abeta neurotoxicity, and therefore
      are potential therapeutic targets to block the interaction of Abeta and p75NTR in
      the pathogenesis of AD.

PMID- 29578486
TI  - Volume and Connectivity of the Ventral Tegmental Area are Linked to
      Neurocognitive Signatures of Alzheimer's Disease in Humans.
AB  - BACKGROUND: There is an urgent need to identify the earliest biological changes
      within the neuropathological cascade of Alzheimer's disease (AD) processes.
      Recent findings in a murine model of AD showed significant preclinical loss of
      dopaminergic neurons in the ventral tegmental area (VTA), accompanied by reduced
      hippocampal innervation and declining memory. It is unknown if these observations
      can be translated in humans. OBJECTIVE: We tested the hypothesis that VTA volume
      is associated with the typical clinical markers of AD in a cohort of patients and
      healthy controls. METHODS: Structural and resting state functional MRI scans, and
      neuropsychological scores were acquired for 51 healthy adults, 30 patients with a
      diagnosis of mild cognitive impairment, and 29 patients with a diagnosis of AD
      dementia. VTA volume was quantified together with other control nuclei. The
      association between nuclei volume, hippocampal size, memory performance, and
      linguistic-executive skills was tested. The effect of VTA functional connectivity
      was also tested. RESULTS: VTA size, but not of control nuclei, yielded a strong
      association with both hippocampal size and memory competence (but not linguistic
      executive performance), and this was particularly strong in healthy adults. In
      addition, functional connectivity between the VTA and hippocampus was
      significantly associated with both markers of AD. CONCLUSION: Diminished
      dopaminergic VTA activity may be crucial for the earliest pathological features
      of AD and might suggest new strategies for early treatment. Memory encoding
      processes may represent cognitive operations susceptible to VTA
      neurodegeneration.

PMID- 29578487
TI  - Call for a Uniform Strategy of Collecting Alzheimer's Disease Costs: A Review and
      Meta-Analysis.
AB  - BACKGROUND: There is now a general attempt in developed countries to implement
      strategic plans to fight against Alzheimer's disease and other dementia
      disorders. Among others, attention is paid to the issues of registers and
      calculations of economic burden. Currently available calculations of costs are
      difficult to compare. The problem is a different breakdown of cost categories and
      non-unified monitoring of cost types. OBJECTIVE: The aim of this paper is to note
      the problem of poor availability and inconsistencies in cost monitoring.
      Furthermore, the intersection of cost items that are comparable and consistently
      monitored in expert studies are specified. METHODS: The Web of Science, Elsevier
      Science Direct, PubMed, and Scopus databases are used in a systematic review. Two
      independent reviewers screened the identified records and selected relevant
      articles published in the period from 2010 to 2016. A meta-analysis of costs is
      performed in four categories related to patients suffering from Alzheimer's
      disease. RESULTS: The resulting estimation of total costs per patient per month
      through meta-analysis is ? 3,896, with 95% CI [2078, 5713]. The highest costs
      arise from informal care following non-medical and medical care. CONCLUSION: The
      results confirm assumption that inconsistencies in cost monitoring of the
      treatment and care of people with dementia exists in Europe. Homogeneity could be
      assumed only in the medical costs of severe patients. Heterogeneity is assumed in
      non-medical costs, informal costs. Cost items should be defined and collected
      more precisely for future more precise monitoring of the economic burden.

PMID- 29578489
TI  - REM Sleep Behavior Disorder and Alzheimer's Disease: Definitely No Relationship?
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia
      characterized by the loss of the typical muscular atonia present during healthy
      REM sleep. RBD can occur in the absence of other neurological conditions or in
      association with a neurodegenerative disorder. It is now well established that
      RBD is a strong predictor of neurodegeneration, in particular synucleinopathies,
      such as Parkinson's disease, Lewy body dementia (LBD), or multiple system
      atrophy. However, some longitudinal studies report that a minority of patients
      develop either overlapping form of dementia or Alzheimer disease's (AD). Although
      AD is reported as a possible development in patients with RBD, it is in a limited
      number of cases and there are concerns about the accuracy of the diagnostic
      criteria. Neuropsychological impairments identified in cross-sectional studies of
      RBD patients describe a profile similar to that observed in dementia related to
      synucleinopathies. However, only deficits in executive function predict the
      development of neurodegeneration. Longitudinal studies reported the development
      of AD in RBD patients in about 7% of cases with variability ranging from 3% and
      11%. Since the majority of longitudinal investigations do not report AD as a
      possible development for RBD patients the proportion may be overestimated. The
      study of the relationship between RBD and AD may be confounded by two factors
      that lead to misdiagnosis: the use of clinical criteria alone and the overlap
      between the clinical features and neuropathology of AD and LBD. Future studies to
      investigate this association must use updated diagnostic criteria incorporating
      ancillary investigations.

PMID- 29578488
TI  - Risk Factors Associated with Cortical Thickness and White Matter Hyperintensities
      in Dementia Free Okinawan Elderly.
AB  - BACKGROUND: Cortical gray matter (GM) and white matter (WM) deterioration are
      signals of neurodegeneration and increased dementia risk; however, their specific
      etiologies in dementia-free aging is unclear. OBJECTIVE: The objective of this
      study was to examine potentially modifiable risk factors of GM and WM
      degeneration in a well-characterized cohort of dementia-free elderly. METHODS: 96
      Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging
      Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of
      inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein),
      cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C
      (HgbA1C), total cholesterol), and essential minerals (copper (Cu), magnesium, and
      calcium) were examined in relation to mean cortical thickness (MCT) and white
      matter hyperintensities (WMH), adjusting for age and gender. Voxel-based
      morphometry (VBM) analyses identified relationships between regional GM density
      and the above markers. RESULTS: Decreased MCT was associated with SBP 140 + (p =
      0.029) and increased serum IL-6 (p = 0.036), HgbA1C (p = 0.002), and Cu (p =
      0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with
      decreased GM density in temporal lobe regions. HgbA1C (p = 0.004) was associated
      with greater WMH volume. CONCLUSIONS: Peripheral markers of Cu, CVD risk, and
      inflammation are associated with MRI-markers of decreased brain health in
      dementia-free Okinawan elderly, with regional cortical thinning in areas involved
      in early accumulation of Alzheimer's disease pathology. Results identify
      potentially modifiable biomarkers as targets in the prevention of dementia in
      older individuals.

PMID- 29578490
TI  - Frontotemporal Dementia and Chorea Associated with a Compound Heterozygous TREM2
      Mutation.
AB  - Frontotemporal dementia (FTD) is clinically characterized by behavioral changes,
      language impairment, and executive dysfunction. FTD usually belongs to the
      frontotemporal lobar degeneration (FTLD) disease group, and its familial forms
      are dominantly inherited and linked to a group of genes relevant to frontal and
      temporal brain pathology, such as MAPT, GRN, C9ORF72, TARDBP, CHMP2B, VCP, and
      FUS. However, FTD can also be associated with different clinical or pathological
      phenotypes caused by mutations in other genes, whose heredity can be dominant or
      recessive. In this work we report on a familial case of FTD characterized by
      behavioral changes and aphasia, very early onset and very long duration, choreic
      movements, and white matter lesions at magnetic resonance imaging. We performed a
      wide-range genetic analysis, using a next generation sequencing approach, to
      evaluate a number of genes involved in neurodegeneration. We found a previously
      unreported compound heterozygous mutation in TREM2, that is commonly associated
      with the recessively inherited Nasu-Hakola disease. We discuss the differential
      diagnosis to be taken into account in cases of FTD presenting with atypical
      features.

PMID- 29578491
TI  - The Impact of Creative Arts in Alzheimer's Disease and Dementia Public Health
      Education.
AB  - Previous research involving dramatic performances about Alzheimer's disease and
      dementia perception have targeted health care workers or caretakers. We examined
      the influence of a theater performance on the emotional affect of a general
      audience to determine the utility of this type of theater in large-scale public
      health education efforts. Our study included 147 participants that attended a
      self-revelatory theater performance based on the social/relationship experiences
      of those with dementia and those who care for them. This type of theater engages
      the audience and actors in a dual transformative process, supporting the
      emotional growth of all involved. Participants completed pre- and post
      performance questionnaires regarding their beliefs and feelings surrounding the
      topic of dementia and the importance of the Arts for educating on issues
      surrounding dementia care. We tested for change in emotional affect pre- and post
      performance using sensitivity and center of gravity statistical analyses. We
      found a significant change in emotional affect from an initial strong negative
      affect to slightly more positive/relaxed view after viewing the performance.
      Findings support self-revelatory theater as a resource to destigmatize
      preconceived notions of dementia. Large-scale community health education efforts
      could benefit from using this style of theater to elicit a change in audience
      perception of disease realities.

PMID- 29578492
TI  - Computer-aided planning with exact implementation into surgical technique in TKA
      is as accurate as intraoperative navigation.
AB  - BACKGROUND: Exact positioning of implants and accuracy of alignment are important
      parameters to provide an long survivorship of endoprostheses after total knee
      arthroplasty. It was suggested that an alignment within 3? from centerline
      provides the best long-term survivorship of TKA. Therefore, computer-assisted
      navigation became more important in TKAs. Another tool to improve the accuracy in
      TKA is the preoperative planning software. OBJECTIVE: Main goal was to determine
      if advantages of an intraoperative navigation system during TKA can be reached by
      an exact implementation of a preoperative computer-aided planning. METHODS: Based
      on all patients (n= 100) underwent primarily TKA in 2015 and 2016 two groups were
      declared: (1) conventionally operated TKA without navigation system and (2)
      operation with an optical navigation system. Data on age, sex, date, operative
      time, severe complications and preoperative vs. postoperative alignment were
      collected retrospectively. RESULTS: The two groups do not differ in postoperative
      alignment and frequency of outliers. Furthermore, there was no difference
      referring to complications and the length of stay in hospital, but operative time
      was prolonged in the navigation-assisted group. CONCLUSIONS: It can be stated
      that conventional surgical techniques in TKA are as accurate as navigated ones if
      an exact preoperative computer aided planning is implemented during surgery.

PMID- 29578493
TI  - Body temperature of healthy men evaluated by thermography: A study of
      reproducibility.
AB  - BACKGROUND: Thermography is a safe, painless, and efficient method for checking
      the temperature of the skin. OBJECTIVE: Was to assess the pattern of skin
      temperature of healthy men, as well as to verify the reproducibility of the
      method. METHODS: This cross-sectional observational study was conducted with 30
      men evaluated by thermography in two moments by using an infrared camera (FLIR
      +T650SC(r)). The skin temperature of 24 regions of interest (ROI) was measured.
      RESULTS: The mean difference in temperature of 10 ROIs in the two evaluations was
      not statistically significant. The comparisons of the DeltaTsk between the right
      and left sides by the two evaluations showed no differences. The intra-class
      correlation coefficient (ICC) between the two moments of evaluation were
      statistically significant, where the dorsal measurements (Left forearm and Right
      dorsal arm) showed poor correlations and the others ranged from moderate to
      strong. Greater reproducibility was confirmed for ventral and dorsal hand ROIs;
      however, they presented the highest coefficient of variation (9% and 8%).
      CONCLUSION: There is a similarity between the temperatures of the ROIs and the
      reproducibility in 22 of the 24 ROIs varies from moderate to strong, showing that
      thermography is a reproducible method in healthy men.

PMID- 29578494
TI  - Patient-specific instruments' routine use over conventional total knee
      arthroplasty remains inconclusive: Analysis of 961 cases.
AB  - BACKGROUND: An increasing demand for total knee arthroplasty (TKA) has pushed
      innovations in the industry and created a promising new technique called patient
      specific instruments (PSI). Early reports had promising results such as reducing
      operative time, cost, and improved alignment. More recent reports are
      conflicting. OBJECTIVE: We aimed to evaluate bleeding, operative time,
      complication rates, and in-hospital stay. METHODS: A monocentric retrospective
      analysis was performed on a total of 961 patients that met inclusion criteria.
      Four different TKA Systems, two of which were performed using conventional
      instrumentation (CI) (n= 768) and two with PSI (n= 193) were trialed under the
      same conditions by three senior surgeons. Operative time, complications,
      bleeding, range of motion, and length of stay were analyzed. RESULTS: There was
      no difference in operative time (p= 0.991) and length of hospital stay (p= 0.371)
      between PSI and CI approaches. Complication rates were lower in the PSI group. CI
      patients showed less non-compensated blood loss (p< 0.001) but required more
      transfusions (5.8% vs. 1.5%, p= 0.014). CONCLUSIONS: There was no difference in
      duration of surgery, length of stay, and total blood loss when performing TKA
      with PSI or CI. There were fewer complications in the PSI group. It remains
      debatable whether these findings justify routine use of PSI in TKA.

PMID- 29578495
TI  - Laser Doppler: A Tool for Measuring Pancreatic Islet Microvascular Vasomotion In
      Vivo.
AB  - As a functional status of microcirculation, microvascular vasomotion is important
      for the delivery of oxygen and nutrients and the removal of carbon dioxide and
      waste products. The impairment of microvascular vasomotion might be a crucial
      step in the development of microcirculation-related diseases. In addition, the
      highly vascularized pancreatic islet is adapted to support endocrine function. In
      this respect, it seems possible to infer that the functional status of pancreatic
      islet microvascular vasomotion might affect pancreatic islet function. Analyzing
      the pathological changes of the functional status of pancreatic islet
      microvascular vasomotion may be a feasible strategy to determine contributions
      that pancreatic islet microcirculation makes to related diseases, such as
      diabetes mellitus, pancreatitis, etc. Therefore, this protocol describes using a
      laser Doppler blood flow monitor to determine the functional status of pancreatic
      islet microvascular vasomotion, and to establish parameters (including average
      blood perfusion, amplitude, frequency, and relative velocity of pancreatic islet
      microvascular vasomotion) for evaluation of the microcirculatory functional
      status. In a streptozotocin-induced diabetic mouse model, we observed an impaired
      functional status of pancreatic islet microvascular vasomotion. In conclusion,
      this approach for assessing pancreatic islet microvascular vasomotion in vivo may
      reveal mechanisms relating to pancreatic islet diseases.

PMID- 29578496
TI  - Focused Ion Beam Fabrication of LiPON-based Solid-state Lithium-ion Nanobatteries
      for In Situ Testing.
AB  - Solid-state electrolytes are a promising replacement for current organic liquid
      electrolytes, enabling higher energy densities and improved safety of lithium-ion
      (Li-ion) batteries. However, a number of setbacks prevent their integration into
      commercial devices. The main limiting factor is due to nanoscale phenomena
      occurring at the electrode/electrolyte interfaces, ultimately leading to
      degradation of battery operation. These key problems are highly challenging to
      observe and characterize as these batteries contain multiple buried interfaces.
      One approach for direct observation of interfacial phenomena in thin film
      batteries is through the fabrication of electrochemically active nanobatteries by
      a focused ion beam (FIB). As such, a reliable technique to fabricate
      nanobatteries was developed and demonstrated in recent work. Herein, a detailed
      protocol with a step-by-step process is presented to enable the reproduction of
      this nanobattery fabrication process. In particular, this technique was applied
      to a thin film battery consisting of LiCoO2/LiPON/a-Si, and has further been
      previously demonstrated by in situ cycling within a transmission electron
      microscope.

PMID- 29578497
TI  - Use of a Psychophysiological Script-driven Imagery Experiment to Study Trauma
      related Dissociation in Borderline Personality Disorder.
AB  - This protocol offers a detailed description of a psychophysiological experiment
      using script-driven trauma-related imagery and standardized clinical instruments
      within a comparative design assessing physiological and psychopathological
      features of individuals with BPD. This method aims at studying the psychological
      and physiological effects of trauma-related dissociation. Since the
      psychodiagnostic classification of trauma-related disorders relies on the
      observation of evolutionarily determined responses to life-threat, an integrated
      assessment paradigm for the study of reactions to traumatic memories proposes a
      very appropriate methodological approach. The employed script-driven imagery
      paradigm uses individual recall instructions to activate trauma-related memory
      networks and prompt associated emotional and physiological responses. These
      responses are measured by means of self-rating scales and physiological
      assessments. During the individual recall, participants are asked to vividly
      imagine traumatic and everyday experiences and other situations triggered by
      short personalized verbal scripts they authored beforehand together with the
      experimenters. A wide range of affective reactions and different physiological
      parameters can be measured. We used this paradigm to investigate dissociative
      states in BPD and to find physiological and affective correlates of dissociative
      states. Some of the participants were having severe traumatic antecedents. To
      investigate different reaction patterns within the same diagnostic group,
      participants with different levels of traumatic histories, symptom severities,
      and co-morbidities should be included. By using short verbal scripts, the level
      of stress induced to participants is held as low as possible without affecting
      the validity of the object of investigation.

PMID- 29578498
TI  - Evaluation of Intracellular Location of Reactive Oxygen Species in Solea
      Senegalensis Spermatozoa.
AB  - Oxidative stress is one of the important factors in decreasing sperm quality.
      Developing efficient protocols for detecting reactive oxygen species (ROS) in
      spermatozoa is of high importance in any species, but these methods are rarely
      used and even less in teleost. Cryopreservation is a useful technique in
      aquaculture for different purposes, including gene banking and guaranteed sperm
      availability throughout the year. Freezing/thawing procedures could cause ROS
      production and damage the sperm cells. Considering the prospective damage that an
      excess of ROS production could cause in spermatozoa depending on their
      localization, here a detailed methodology to detect H2O2 and to evaluate its
      intracellular localization by confocal microscopy is provided. For this purpose,
      a combination of 3 fluorochromes (2',7'-Dichlorodihydrofluorescein diacetate
      (DCFH-DA), a live mitochondria stain and 4',6-Diamidino-2-phenylindole
      dihydrochloride (DAPI)) are used to evaluate the co-localization of H2O2 with
      spermatozoa nuclei or mitochondria in Solea senegalesis sperm samples.

PMID- 29578499
TI  - Processing of Bulk Nanocrystalline Metals at the US Army Research Laboratory.
AB  - Given their potential for significant property improvements relative to their
      large grained counterparts, much work has been devoted to the continued
      development of nanocrystalline metals. Despite these efforts, the transition of
      these materials from the lab bench to actual applications has been blocked by the
      inability to produce large scale parts that retain the desired nanocrystalline
      microstructures. Following the development of a method proven to stabilize the
      nanosized grain structure to temperatures approaching that of the melting point
      for the given metal, the US Army Research Laboratory (ARL) has progressed to the
      next stage in the development of these materials - namely the production of large
      scale parts suitable for testing and evaluation in a range of relevant test
      environments. This report provides a broad overview of the ongoing efforts in the
      processing, characterization, and consolidation of these materials at ARL. In
      particular, focus is placed on the methodology used for producing the
      nanocrystalline metal powders, in both small and large-scale amounts, that are at
      the center of ongoing research efforts.

PMID- 29578501
TI  - Capturing the Interaction Kinetics of an Ion Channel Protein with Small Molecules
      by the Bio-layer Interferometry Assay.
AB  - The bio-layer interferometry (BLI) assay is a valuable tool for measuring protein
      protein and protein-small molecule interactions. Here, we first describe the
      application of this novel label-free technique to study the interaction of human
      EAG1 (hEAG1) channel proteins with the small molecule PIP2. hEAG1 channel has
      been recognized as potential therapeutic target because of its aberrant
      overexpression in cancers and a few gain-of-function mutations involved in some
      types of neurological diseases. We purified hEAG1 channel proteins from a
      mammalian stable expression system and measured the interaction with PIP2 by BLI.
      The successful measurement of the kinetics of binding between hEAG1 protein and
      PIP2 demonstrates that the BLI assay is a potential high-throughput approach used
      for novel small-molecule ligand screening in ion channel pharmacology.

PMID- 29578500
TI  - Practical Considerations in Studying Metastatic Lung Colonization in Osteosarcoma
      Using the Pulmonary Metastasis Assay.
AB  - The pulmonary metastasis assay (PuMA) is an ex vivo lung explant and closed cell
      culture system that permits researchers to study the biology of lung colonization
      in osteosarcoma (OS) by fluorescence microscopy. This article provides a detailed
      description of the protocol, and discusses examples of obtaining image data on
      metastatic growth using widefield or confocal fluorescence microscopy platforms.
      The flexibility of the PuMA model permits researchers to study not only the
      growth of OS cells in the lung microenvironment, but also to assess the effects
      of anti-metastatic therapeutics over time. Confocal microscopy allows for
      unprecedented, high-resolution imaging of OS cell interactions with the lung
      parenchyma. Moreover, when the PuMA model is combined with fluorescent dyes or
      fluorescent protein genetic reporters, researchers can study the lung
      microenvironment, cellular and subcellular structures, gene function, and
      promoter activity in metastatic OS cells. The PuMA model provides a new tool for
      osteosarcoma researchers to discover new metastasis biology and assess the
      activity of novel anti-metastatic, targeted therapies.

PMID- 29578502
TI  - Improvement of a Closed Chest Porcine Myocardial Infarction Model by
      Standardization of Tissue and Blood Sampling Procedures.
AB  - Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the
      necrotic area after myocardial infarction. To date there is no approved drug to
      prevent or reduce myocardial I/R injury. The study and understanding of the
      pathophysiological mechanisms of myocardial I/R injury is essential to develop
      successful treatments. Large animal experiments are an important step in
      translational methods. The porcine model of acute myocardial infarction has been
      established and described by ourselves and others. We aimed to further improve
      the value of the model by focusing in detail on the sampling techniques for use
      in future experiments. Furthermore, we emphasize small but important steps that
      can affect the quality of the final results. To mimic the clinical situation of
      myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was
      inserted into the left anterior descending coronary artery (LAD) of an
      anesthetized pig.  degrees  degrees  degrees This model mimics acute myocardial
      infarction and PCI treatment in humans with the possibility of accurately
      determining the area at risk as well as the necrotic- and viable ischemic tissue.
      Here the model was used to investigate the effect of a bicyclic peptide inhibitor
      of FXIIa. The model can also be modified to allow longer reperfusion times to
      study later effects of myocardial infarction.

PMID- 29578503
TI  - Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in
      Drosophila Melanogaster.
AB  - Protein aggregation is a central feature of most neurodegenerative diseases,
      including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's
      disease (HD), and amyotrophic lateral sclerosis (ALS). Protein aggregates are
      closely associated with neuropathology in these diseases, although the exact
      mechanism by which aberrant protein aggregation disrupts normal cellular
      homeostasis is not known. Emerging data provide strong support for the hypothesis
      that pathogenic aggregates in AD, PD, HD, and ALS have many similarities to
      prions, which are protein-only infectious agents responsible for the
      transmissible spongiform encephalopathies. Prions self-replicate by templating
      the conversion of natively-folded versions of the same protein, causing spread of
      the aggregation phenotype. How prions and prion-like proteins in AD, PD, HD, and
      ALS move from one cell to another is currently an area of intense investigation.
      Here, a Drosophila melanogaster model that permits monitoring of prion-like, cell
      to-cell transmission of mutant huntingtin (Htt) aggregates associated with HD is
      described. This model takes advantage of powerful tools for manipulating
      transgene expression in many different Drosophila tissues and utilizes a
      fluorescently-tagged cytoplasmic protein to directly report prion-like transfer
      of mutant Htt aggregates. Importantly, the approach we describe here can be used
      to identify novel genes and pathways that mediate spreading of protein aggregates
      between diverse cell types in vivo. Information gained from these studies will
      expand the limited understanding of the pathogenic mechanisms that underlie
      neurodegenerative diseases and reveal new opportunities for therapeutic
      intervention.

PMID- 29578504
TI  - Ultrasonic Fatigue Testing in the Tension-Compression Mode.
AB  - Ultrasonic fatigue testing is one of a few methods which allow investigating
      fatigue properties in the ultra-high cycle region. The method is based on
      exposing the specimen to longitudinal vibrations on its resonance frequency close
      to 20 kHz. With use of this method, it is possible to significantly decrease the
      time required for the test, when compared to conventional testing devices usually
      working at frequencies under 200 Hz. It is also used to simulate loading of
      material during operation in high speed conditions, such as those experienced by
      components of jet engines or car turbo pumps. It is necessary to operate only in
      the high and ultra-high cycle region, due to the possibility of extremely high
      deformation rates, which can have a significant influence on the test results.
      Specimen shape and dimensions have to be carefully selected and calculated to
      fulfill the resonance condition of the ultrasonic system; thus, it is not
      possible to test the full components or specimens of arbitrary shape. Before each
      test, it is necessary to harmonize the specimen with the frequency of the
      ultrasonic system to compensate for deviations of the real shape from the ideal
      one. It is not possible to run a test until a total fracture of the specimen,
      since the test is automatically terminated after initiation and propagation of
      the crack to a certain length, when the stiffness of the system changes enough to
      shift the system out of the resonance frequency. This manuscript describes the
      process of evaluation of materials' fatigue properties at high-frequency
      ultrasonic fatigue loading with use of mechanical resonance at a frequency close
      to 20 kHz. The protocol includes a detailed description of all steps required for
      a correct test, including specimen design, stress calculation, harmonizing with
      the resonance frequency, performing the test, and final static fracture.

PMID- 29578505
TI  - Robust DNA Isolation and High-throughput Sequencing Library Construction for
      Herbarium Specimens.
AB  - Herbaria are an invaluable source of plant material that can be used in a variety
      of biological studies. The use of herbarium specimens is associated with a number
      of challenges including sample preservation quality, degraded DNA, and
      destructive sampling of rare specimens. In order to more effectively use
      herbarium material in large sequencing projects, a dependable and scalable method
      of DNA isolation and library preparation is needed. This paper demonstrates a
      robust, beginning-to-end protocol for DNA isolation and high-throughput library
      construction from herbarium specimens that does not require modification for
      individual samples. This protocol is tailored for low quality dried plant
      material and takes advantage of existing methods by optimizing tissue grinding,
      modifying library size selection, and introducing an optional reamplification
      step for low yield libraries. Reamplification of low yield DNA libraries can
      rescue samples derived from irreplaceable and potentially valuable herbarium
      specimens, negating the need for additional destructive sampling and without
      introducing discernible sequencing bias for common phylogenetic applications. The
      protocol has been tested on hundreds of grass species, but is expected to be
      adaptable for use in other plant lineages after verification. This protocol can
      be limited by extremely degraded DNA, where fragments do not exist in the desired
      size range, and by secondary metabolites present in some plant material that
      inhibit clean DNA isolation. Overall, this protocol introduces a fast and
      comprehensive method that allows for DNA isolation and library preparation of 24
      samples in less than 13 h, with only 8 h of active hands-on time with minimal
      modifications.

PMID- 29578506
TI  - CRISPR/Cas9-mediated Targeted Integration In Vivo Using a Homology-mediated End
      Joining-based Strategy.
AB  - As a promising genome editing platform, the CRISPR/Cas9 system has great
      potential for efficient genetic manipulation, especially for targeted integration
      of transgenes. However, due to the low efficiency of homologous recombination
      (HR) and various indel mutations of non-homologous end joining (NHEJ)-based
      strategies in non-dividing cells, in vivo genome editing remains a great
      challenge. Here, we describe a homology-mediated end joining (HMEJ)-based
      CRISPR/Cas9 system for efficient in vivo precise targeted integration. In this
      system, the targeted genome and the donor vector containing homology arms (~800
      bp) flanked by single guide RNA (sgRNA) target sequences are cleaved by
      CRISPR/Cas9. This HMEJ-based strategy achieves efficient transgene integration in
      mouse zygotes, as well as in hepatocytes in vivo. Moreover, a HMEJ-based strategy
      offers an efficient approach for correction of fumarylacetoacetate hydrolase
      (Fah) mutation in the hepatocytes and rescues Fah-deficiency induced liver
      failure mice. Taken together, focusing on targeted integration, this HMEJ-based
      strategy provides a promising tool for a variety of applications, including
      generation of genetically modified animal models and targeted gene therapies.

PMID- 29578507
TI  - Real-time Breath Analysis by Using Secondary Nanoelectrospray Ionization Coupled
      to High Resolution Mass Spectrometry.
AB  - Exhaled volatile organic compounds (VOCs) have aroused considerable interest,
      since they can serve as biomarkers for disease diagnosis and environmental
      exposure in a non-invasive manner. In this work, we present a protocol to
      characterize the exhaled VOCs in real time by using secondary nanoelectrospray
      ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS). The
      homemade Sec-nanoESI source was readily set up based on a commercial nanoESI
      source. Hundreds of peaks were observed in the background-subtracted mass spectra
      of exhaled breath, and the mass accuracy values are -4.0-13.5 ppm and -20.3-1.3
      ppm in the positive and negative ion detection modes, respectively. The peaks
      were assigned with accurate elemental composition according to the accurate mass
      and isotopic pattern. Less than 30 s is used for one exhalation measurement, and
      it takes approximately 7 min for six replicated measurements.

PMID- 29578508
TI  - Regeneration of Arrayed Gold Microelectrodes Equipped for a Real-Time Cell
      Analyzer.
AB  - The label-free cell-based assay is advantageous for biochemical study because of
      it does not require the use of experimental animals. Due to its ability to
      provide more dynamic information about cells under physiological conditions than
      classical biochemical assays, this label-free real-time cell assay based on the
      electric impedance principle is attracting more attention during the past decade.
      However, its practical utilization may be limited due to the relatively expensive
      cost of measurement, in which costly consumable disposable gold microchips are
      used for the cell analyzer. In this protocol, we have developed a general
      strategy to regenerate arrayed gold microelectrodes equipped for a commercial
      label-free cell analyzer. The regeneration process includes trypsin digestion,
      rinsing with ethanol and water, and a spinning step. The proposed method has been
      tested and shown to be effective for the regeneration and repeated usage of
      commercial electronic plates at least three times, which will help researchers
      save on the high running cost of real-time cell assays.

PMID- 29578509
TI  - Real-time Analysis of Transcription Factor Binding, Transcription, Translation,
      and Turnover to Display Global Events During Cellular Activation.
AB  - Upon activation, cells rapidly change their functional programs and, thereby,
      their gene expression profile. Massive changes in gene expression occur, for
      example, during cellular differentiation, morphogenesis, and functional
      stimulation (such as activation of immune cells), or after exposure to drugs and
      other factors from the local environment. Depending on the stimulus and cell
      type, these changes occur rapidly and at any possible level of gene regulation.
      Displaying all molecular processes of a responding cell to a certain type of
      stimulus/drug is one of the hardest tasks in molecular biology. Here, we describe
      a protocol that enables the simultaneous analysis of multiple layers of gene
      regulation. We compare, in particular, transcription factor binding (Chromatin
      immunoprecipitation-sequencing (ChIP-seq)), de novo transcription (4-thiouridine
      sequencing (4sU-seq)), mRNA processing, and turnover as well as translation
      (ribosome profiling). By combining these methods, it is possible to display a
      detailed and genome-wide course of action. Sequencing newly transcribed RNA is
      especially recommended when analyzing rapidly adapting or changing systems, since
      this depicts the transcriptional activity of all genes during the time of 4sU
      exposure (irrespective of whether they are up- or downregulated). The
      combinatorial use of total RNA-seq and ribosome profiling additionally allows the
      calculation of RNA turnover and translation rates. Bioinformatic analysis of high
      throughput sequencing results allows for many means for analysis and
      interpretation of the data. The generated data also enables tracking co
      transcriptional and alternative splicing, just to mention a few possible
      outcomes. The combined approach described here can be applied for different model
      organisms or cell types, including primary cells. Furthermore, we provide
      detailed protocols for each method used, including quality controls, and discuss
      potential problems and pitfalls.

PMID- 29578510
TI  - Imaging Intermediate Filaments and Microtubules with 2-dimensional Direct
      Stochastic Optical Reconstruction Microscopy.
AB  - The cytoskeleton, composed of actin microfilaments, microtubules, and
      intermediate filaments (IF), plays a key role in the control of cell shape,
      polarity, and motility. The organization of the actin and microtubule networks
      has been extensively studied but that of IFs is not yet fully characterized. IFs
      have an average diameter of 10 nm and form a network extending throughout the
      cell cytoplasm. They are physically associated with actin and microtubules
      through molecular motors and cytoskeletal linkers. This tight association is at
      the heart of the regulatory mechanisms that ensure the coordinated regulation of
      the three cytoskeletal networks required for most cell functions. It is therefore
      crucial to visualize IFs alone and also together with each of the other
      cytoskeletal networks. However, IF networks are extremely dense in most cell
      types, especially in glial cells, which makes its resolution very difficult to
      achieve with standard fluorescence microscopy (lateral resolution of ~250 nm).
      Direct STochastic Optical Reconstruction Microscopy (dSTORM) is a technique
      allowing a gain in lateral resolution of one order of magnitude. Here, we show
      that lateral dSTORM resolution is sufficient to resolve the dense organization of
      the IF networks and, in particular, of IF bundles surrounding microtubules. Such
      tight association is likely to participate in the coordinated regulation of these
      two networks and may, explain how vimentin IFs template and stabilize microtubule
      organization as well as could influence microtubule dependent vesicular
      trafficking. More generally, we show how the observation of two cytoskeletal
      components with dual-color dSTORM technique brings new insight into their mutual
      interaction.

PMID- 29578511
TI  - Surgical Treatment for Benign Prostatic Hyperplasia: Holmium Laser Enucleation of
      the Prostate (HoLEP).
AB  - Benign prostatic hyperplasia (BPH) commonly occurs among elderly males. The
      condition causes symptoms in the lower urinary tract, thereby reducing the
      quality of life. BPH includes 2 major treatments: medication and surgery.
      Surgical treatment is often the most effective and final intervention. Holmium
      laser enucleation of the prostate (HoLEP), one of the most efficient surgical
      procedures for BPH, is conducted transurethrally. During surgery, the most
      important and most difficult part is to locate the surgical capsule of the
      prostate, which is consistent to the idea of anatomic surgery. Different skills
      may be needed in treating different parts of the prostate. HoLEP tends to be
      efficient and safe with good hemostatic properties, and able to treat bladder
      calculus, which may be the complications of BPH. The technique is particularly
      suitable for prostate of varying volumes and sizes. Indeed, HoLEP also presents
      certain disadvantages, such as a long learning curve and costly equipment.
      Regardless, this method may be the "new standard" and the excellent method for
      the surgical treatment of BPH.

PMID- 29578512
TI  - Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low
      dose Toxicants.
AB  - Bisphenols, such as bisphenol A (BPA) and bisphenol S (BPS) are polymerizing
      agents widely used in the production of plastics and numerous everyday-use
      products. Based on their chemical structure and estradiol-like biological
      properties, they have been classified as endocrine disrupting compounds (EDC).
      Long-term exposure to EDCs, even at low doses, has been linked to various health
      defects including cancer, behavioral disorders and infertility, with greater
      vulnerability indicated during early developmental periods. Cellular and
      molecular studies with the genetically tractable nematode model Caenorhabditis
      elegans have demonstrated that exposure to BPA causes apoptosis, embryonic
      lethality and disruption in the DNA repair mechanisms. We have previously
      reported that exposure of C. elegans embryos to low doses of different bisphenols
      decreases fecundity. In addition, we have shown that the effects of exposure
      during the very early stages of development persist into adulthood as assayed by
      quantifying habituation behavior, a form of non-associative learning. Here, we
      provide detailed protocols for embryonic exposure to low-dose EDCs as well as the
      associated fecundity and anterior touch habituation assays, along with
      representative results.

PMID- 29578513
TI  - Puncture-Induced Iris Neovascularization as a Mouse Model of Rubeosis Iridis.
AB  - We describe a model of puncture-induced iris neovascularization as a general
      model for noninvasive evaluation of angiogenesis. The model is also relevant for
      targeting neovascular glaucoma, a sight-threatening complication of diabetic
      retinopathy. This method is based on the induction of iris vascular response by a
      series of self-sealing uveal punctures on BALB/c mice and takes advantage of the
      postpartum maturation of mouse ocular vasculature. Mouse pups undergo uveal
      punctures from postnatal day 12.5, when the pups naturally open their eyes, until
      postnatal day 24.5. Due to the transparency of the cornea, iris vasculature can
      be analyzed easily through time by noninvasive in vivo methods. Furthermore, the
      semitransparent iris of BALB/c mice can be flatmounted for detailed
      immunohistologic analysis with minimal non-specific background staining. In this
      model, angiogenesis is mainly driven by the inflammatory and plasminogen
      activating systems. The puncture-induced model is the first to induce iris
      neovascularization in small rodents, and has the advantage of allowing direct
      noninvasive in vivo analysis of the angiogenic process. Moreover, the model can
      be combined with angiogenic modulating substances, which highlights its potential
      in the study of angiogenesis with an in vivo perspective.

PMID- 29578514
TI  - Mechanical Ventilation Boot Camp Curriculum.
AB  - Medical management of mechanically ventilated patients is challenging to novice
      providers. Incorrect management of this population may lead to increased
      morbidity and mortality. A three-day simulation-based boot camp serves to provide
      one-on-one instruction with a critical care provider. These intensivists may
      dispense personalized immediate feedback as learners engage in hands-on practice
      with a real mechanical ventilator. Multiple different pathologies can be reviewed
      that may not be encountered in the clinical setting. Learners can visualize
      immediate consequences of their actions and may troubleshoot and ask questions,
      all while in a safe learning environment. We describe the use of human-patient
      simulators connected to breathing simulators and mechanical ventilators.
      Potential curriculum executors should be aware of the cost of the equipment and
      the time needed to dedicate to boot camp execution; however, this intensive
      interactive training has been shown to increase provider competency, knowledge,
      and confidence in ventilator management. This curriculum outline provides
      guidance on how to execute a simulation-based boot camp to train providers on the
      management of mechanically ventilated patients.

PMID- 29578515
TI  - A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen
      dependent and Castration-resistant Prostate Cancer.
AB  - Orthotopic tumor modeling is a valuable tool for pre-clinical prostate cancer
      research, as it has multiple advantages over both subcutaneous and transgenic
      genetically engineered mouse models. Unlike subcutaneous tumors, orthotopic
      tumors contain more clinically accurate vasculature, tumor microenvironment, and
      responses to multiple therapies. In contrast to genetically engineered mouse
      models, orthotopic models can be performed with lower cost and in less time,
      involve the use of highly complex and heterogeneous mouse or human cancer cell
      lines, rather that single genetic alterations, and these cell lines can be
      genetically modified, such as to express imaging agents. Here, we present a
      protocol to surgically injecting a luciferase- and mCherry-expressing murine
      prostate cancer cell line into the anterior prostate lobe of mice. These mice
      developed orthotopic tumors that were non-invasively monitored in vivo and
      further analyzed for tumor volume, weight, mouse survival, and immune
      infiltration. Further, orthotopic tumor-bearing mice were surgically castrated,
      leading to immediate tumor regression and subsequent recurrence, representing
      castration-resistant prostate cancer. Although technical skill is required to
      carry out this procedure, this syngeneic orthotopic model of both androgen
      dependent and castration-resistant prostate cancer is of great use to all
      investigators in the field.

PMID- 29578516
TI  - A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of
      Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4.
AB  - Pharmacological targeting of G protein-coupled receptors (GPCRs) is of great
      importance to human health, as dysfunctional GPCR-mediated signaling contributes
      to the progression of many diseases. The ligand/receptor pair CXC chemokine
      ligand 12 (CXCL12)/CXC chemokine receptor 4 (CXCR4) has raised significant
      clinical interest, for instance as a potential target for the treatment of cancer
      and inflammatory diseases. Small molecules as well as therapeutic antibodies that
      specifically target CXCR4 and inhibit the receptor's function are therefore
      considered to be valuable pharmacological tools. Here, a flow cytometry-based
      cellular assay that allows identification of compounds (e.g., small molecules)
      that abrogate CXCL12 binding to CXCR4, is described. Essentially, the assay
      relies on the competition for receptor binding between a fixed amount of
      fluorescently labeled CXCL12, the natural chemokine agonist for CXCR4, and
      unlabeled compounds. Hence, the undesirable use of radioactively labeled probes
      is avoided in this assay. In addition, living cells are used as the source of
      receptor (CXCR4) instead of cell membrane preparations. This allows easy
      adaptation of the assay to a plate format, which increases the throughput. This
      assay has been shown to be a valuable generic drug discovery assay to identify
      CXCR4-targeting compounds. The protocol can likely be adapted to other GPCRs, at
      least if fluorescently labeled ligands are available or can be generated. Prior
      knowledge concerning the intracellular signaling pathways that are induced upon
      activation of these GPCRs, is not required.

PMID- 29578517
TI  - Rapid Nanoprobe Signal Enhancement by In Situ Gold Nanoparticle Synthesis.
AB  - The use of nanoprobes such as gold, silver, silica or iron-oxide nanoparticles as
      detection reagents in bioanalytical assays can enable high sensitivity and
      convenient colorimetric readout. However, high densities of nanoparticles are
      typically needed for detection. The available synthesis-based enhancement
      protocols are either limited to gold and silver nanoparticles or rely on precise
      enzymatic control and optimization. Here, we present a protocol to enhance the
      colorimetric readout of gold, silver, silica, and iron oxide nanoprobes. It was
      observed that the colorimetric signal can be improved by up to a 10000-fold
      factor. The basis for such signal enhancement strategies is the chemical
      reduction of Au3+ to Au0. There are several chemical reactions that enable the
      reduction of Au3+ to Au0. In the protocol, Good's buffers and H2O2 are used and
      it is possible to favor the deposition of Au0 onto the surface of existing
      nanoprobes, in detriment of the formation of new gold nanoparticles. The protocol
      consists of the incubation of the microarray with a solution consisting of
      chloroauric acid and H2O2 in 2-(N-morpholino)ethanesulfonic acid pH 6 buffer
      following the nanoprobe-based detection assay. The enhancement solution can be
      applied to paper and glass-based sensors. Moreover, it can be used in
      commercially available immunoassays as demonstrated by the application of the
      method to a commercial allergen microarray. The signal development requires less
      than 5 min of incubation with the enhancement solution and the readout can be
      assessed by naked eye or low-end image acquisition devices such as a table-top
      scanner or a digital camera.

PMID- 29578518
TI  - Measuring Endoreduplication by Flow Cytometry of Isolated Tuber Protoplasts.
AB  - Endoreduplication, the replication of a cell's nuclear genome without subsequent
      cytokinesis, yields cells with increased DNA content and is associated with
      specialization, development and increase in cellular size. In plants,
      endoreduplication seems to facilitate the growth and expansion of certain tissues
      and organs. Among them is the tuber of potato (Solanum tuberosum), which
      undergoes considerable cellular expansion in fulfilling its function of
      carbohydrate storage. Thus, endoreduplication may play an important role in how
      tubers are able to accommodate this abundance of carbon. However, the cellular
      debris resulting from crude nuclear isolation methods of tubers, methods that can
      be used effectively with leaves, precludes the estimation of the tuber
      endoreduplication index (EI). This article presents a technique for assessing
      tuber endoreduplication through the isolation of protoplasts while demonstrating
      representative results obtained from different genotypes and compartmentalized
      tuber tissues. The major limitations of the protocol are the time and reagent
      costs required for sample preparation as well as relatively short lifespan of
      samples after lysis of protoplasts. While the protocol is sensitive to technical
      variation, it represents an improvement over traditional methods of nuclear
      isolation from these large specialized cells. Possibilities for improvements to
      the protocol such as recycling enzyme, the use of fixatives, and other
      alterations are proposed.

PMID- 29578519
TI  - Isolation and Culture of Rodent Microglia to Promote a Dynamic Ramified
      Morphology in Serum-free Medium.
AB  - Microglia represent 5 - 10% of all central nervous system (CNS) cells and are
      increasingly drawing attention due to their contributions during development,
      homeostasis, and disease. Although macrophages have been studied in detail for
      decades, specialized features of microglia, the tissue-resident macrophages of
      the CNS, have remained largely mysterious, in part due to limitations in the
      ability to recapitulate mature microglial properties in culture. Here, we
      illustrate a straightforward procedure for the rapid isolation of pure microglia
      from the mature rodent brain. We also describe serum-free culture conditions that
      support high levels of microglial viability over time. Microglia cultured under
      these defined-medium conditions exhibit elaborate ramified processes and dynamic
      surveillance behavior. We illustrate some effects of serum exposure on cultured
      microglia and discuss how these serum-free cultures compare to both serum-exposed
      cultures as well as microglia in vivo.

PMID- 29578520
TI  - Mobile Game-based Virtual Reality Program for Upper Extremity Stroke
      Rehabilitation.
AB  - Stroke rehabilitation requires repetitive, intensive, goal-oriented therapy.
      Virtual reality (VR) has the potential to satisfy these requirements. Game-based
      therapy can promote patients' engagement in rehabilitation therapy as a more
      interesting and a motivating tool. Mobile devices such as smartphones and tablet
      PCs can provide personalized home-based therapy with interactive communication
      between patients and clinicians. In this study, a mobile VR upper extremity
      rehabilitation program using game applications was developed. The findings from
      the study show that the mobile game-based VR program effectively promotes upper
      extremity recovery in patients with stroke. In addition, patients completed two
      weeks of treatment using the program without adverse effects and were generally
      satisfied with the program. This mobile game-based VR upper extremity
      rehabilitation program can substitute for some parts of the conventional therapy
      that are delivered one-on-one by an occupational therapist. This time-efficient,
      easy to implement, and clinically effective program would be a good candidate
      tool for tele-rehabilitation for upper extremity recovery in patients with
      stroke. Patients and therapists can collaborate remotely through these e-health
      rehabilitation programs while reducing economic and social costs.

PMID- 29578521
TI  - Detection of Detergent-sensitive Interactions Between Membrane Proteins.
AB  - Our ability to explore protein-protein interactions is the key to understanding
      regulatory connections in the cell. However, detection of protein-protein
      interactions in many cases is associated with significant experimental
      challenges. In particular, sorting receptors interact with their protein cargo in
      the lumen of the membrane compartments often in a detergent-sensitive fashion,
      making co-immunoprecipitation of these proteins unusable. Binding of the sorting
      receptor sortilin to glucose transporter GLUT4 may serve as an example of weak
      luminal interactions between membrane proteins. Here, we describe a fast, simple,
      and inexpensive assay to validate the interaction between sortilin and GLUT4. For
      that, we have designed and chemically synthesized the myc-tagged peptide
      corresponding to the potential sortilin-binding epitope in the luminal part of
      GLUT4. Sortilin tagged with six histidines was expressed in mammalian cells, and
      isolated from cell lysates using Cobalt beads. Sortilin immobilized on the beads
      was incubated with the peptide solution at different pH values, and the eluted
      material was analyzed by Western blotting. This assay can be easily adapted to
      study other detergent-sensitive protein-protein interactions.

PMID- 29578522
TI  - Histological Quantification to Determine Lung Fungal Burden in Experimental
      Aspergillosis.
AB  - The quantification of lung fungal burden is critical for the determination of the
      relative levels of immune protection and fungal virulence in mouse models of
      pulmonary fungal infection. Although multiple methods are used to assess fungal
      burden, quantitative polymerase chain reaction (qPCR) of fungal DNA has emerged
      as a technique with several advantages over previous culture-based methods.
      Currently, a comprehensive assessment of lung pathology, leukocyte recruitment,
      fungal burden, and gene expression in mice with invasive aspergillosis (IA)
      necessitates the use of a significant number of experimental and control animals.
      Here the quantification of lung histological staining to determine fungal burden
      using a reduced number of animals was examined in detail. Lung sections were
      stained to identify fungal structures with Gomori's modified methanamine silver
      (GMS) staining. Images were taken from the GMS-stained sections from 4 discrete
      fields of each formalin-fixed paraffin-embedded lung. The GMS stained areas
      within each image were quantified using an image analysis program, and from this
      quantification, the mean percentage of stained area was determined for each
      sample. Using this strategy, eosinophil-deficient mice exhibited decreased fungal
      burden and disease with caspofungin therapy, while wild-type mice with IA did not
      improve with caspofungin. Similarly, fungal burden in mice lacking gammadelta T
      cells were also improved by caspofungin, as measured by qPCR and GMS
      quantification. GMS quantification is therefore introduced as a method for the
      determination of relative lung fungal burden that may ultimately reduce the
      quantity of experimental animals required for comprehensive studies of invasive
      aspergillosis.

PMID- 29578523
TI  - Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides
      for Increasing Cellular Accumulation and Improving Tumor Targeting.
AB  - Antibody-conjugates (ACs) modified with virus-derived peptides are a potentially
      powerful class of tumor cell delivery agents for molecular payloads used in
      cancer treatment and imaging due to increased cellular accumulation over current
      ACs. During early AC in vitro development, fluorescence techniques and
      radioimmunoassays are sufficient for determining intracellular localization,
      accumulation efficiency, and target cell specificity. Currently, there is no
      consensus on standardized methods for preparing cells for evaluating AC
      intracellular accumulation and localization. The initial testing of ACs modified
      with virus-derived peptides is critical especially if several candidates have
      been constructed. Determining intracellular accumulation by fluorescence can be
      affected by background signal from ACs at the cell surface and complicate the
      interpretation of accumulation. For radioimmunoassays, typically treated cells
      are fractionated and the radioactivity in different cell compartments measured.
      However, cell lysis varies from cell to cell and often nuclear and cytoplasmic
      compartments are not adequately isolated. This can produce misleading data on
      payload delivery properties. The intravenous injection of radiolabeled virus
      derived peptide-modified ACs in tumor bearing mice followed by radionuclide
      imaging is a powerful method for determining tumor targeting and payload delivery
      properties at the in vivo phase of development. However, this is a relatively
      recent advancement and few groups have evaluated virus-derived peptide-modified
      ACs in this manner. We describe the processing of treated cells to more
      accurately evaluate virus-derived peptide-modified AC accumulation when using
      confocal microscopy and radioimmunoassays. Specifically, a method for
      trypsinizing cells to remove cell surface bound ACs. We also provide a method for
      improving cellular fractionation. Lastly, this protocol provides an in vivo
      method using positron emission tomography (PET) for evaluating initial tumor
      targeting properties in tumor-bearing mice. We use the radioisotope 64Cu (t1/2 =
      12.7 h) as an example payload in this protocol.

PMID- 29578524
TI  - Sampling Strategies and Processing of Biobank Tissue Samples from Porcine
      Biomedical Models.
AB  - In translational medical research, porcine models have steadily become more
      popular. Considering the high value of individual animals, particularly of
      genetically modified pig models, and the often-limited number of available
      animals of these models, establishment of (biobank) collections of adequately
      processed tissue samples suited for a broad spectrum of subsequent analyses
      methods, including analyses not specified at the time point of sampling,
      represent meaningful approaches to take full advantage of the translational value
      of the model. With respect to the peculiarities of porcine anatomy, comprehensive
      guidelines have recently been established for standardized generation of
      representative, high-quality samples from different porcine organs and tissues.
      These guidelines are essential prerequisites for the reproducibility of results
      and their comparability between different studies and investigators. The
      recording of basic data, such as organ weights and volumes, the determination of
      the sampling locations and of the numbers of tissue samples to be generated, as
      well as their orientation, size, processing and trimming directions, are relevant
      factors determining the generalizability and usability of the specimen for
      molecular, qualitative, and quantitative morphological analyses. Here, an
      illustrative, practical, step-by-step demonstration of the most important
      techniques for generation of representative, multi-purpose biobank specimen from
      porcine tissues is presented. The methods described here include determination of
      organ/tissue volumes and densities, the application of a volume-weighted
      systematic random sampling procedure for parenchymal organs by point-counting,
      determination of the extent of tissue shrinkage related to histological embedding
      of samples, and generation of randomly oriented samples for quantitative
      stereological analyses, such as isotropic uniform random (IUR) sections generated
      by the "Orientator" and "Isector" methods, and vertical uniform random (VUR)
      sections.

PMID- 29578525
TI  - Characterization of Immune Cells in Human Adipose Tissue by Using Flow Cytometry.
AB  - Infiltration of immune cells in the subcutaneous and visceral adipose tissue (AT)
      deposits leads to a low-grade inflammation contributing to the development of
      obesity-associated complications such as type 2 diabetes. To quantitatively and
      qualitatively investigate the immune cell subsets in human AT deposits, we have
      developed a flow cytometry approach. The stromal vascular fraction (SVF),
      containing the immune cells, is isolated from subcutaneous and visceral AT
      biopsies by collagenase digestion. Adipocytes are removed after centrifugation.
      The SVF cells are stained for multiple membrane-bound markers selected to
      differentiate between immune cell subsets and analyzed using flow cytometry. As a
      result of this approach, pro- and anti-inflammatory macrophage subsets, dendritic
      cells (DCs), B-cells, CD4+ and CD8+ T-cells, and NK cells can be detected and
      quantified. This method gives detailed information about immune cells in AT and
      the amount of each specific subset. Since there are numerous fluorescent
      antibodies available, our flow cytometry approach can be adjusted to measure
      various other cellular and intracellular markers of interest.

PMID- 29578526
TI  - An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of
      Ischemic Stroke.
AB  - Ischemic stroke leads to vasogenic cerebral edema and subsequent primary brain
      injury, which is mediated through destruction of the blood-brain barrier (BBB).
      Rats with induced ischemic stroke were established and used as in vivo models to
      investigate the functional integrity of the BBB. Spectrophotometric detection of
      Evans blue (EB) in the brain samples with ischemic injury could provide reliable
      justification for the research and development of novel therapeutic modalities.
      This method generates reproducible results, and is applicable in any laboratory
      without a need for special equipment. Here, we present a visualized and technical
      guideline on the detection of the extravasation of EB following induction of
      ischemic stroke in rats.

PMID- 29578527
TI  - Adult Mouse DRG Explant and Dissociated Cell Models to Investigate
      Neuroplasticity and Responses to Environmental Insults Including Viral Infection.
AB  - This protocol describes an ex vivo model of mouse-derived dorsal root ganglia
      (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons
      and glial satellite cells. These are useful and versatile models to investigate a
      variety of biological responses associated with physiological and pathological
      conditions of the peripheral nervous system (PNS) ranging from neuron-glial
      interaction, neuroplasticity, neuroinflammation, and viral infection. The usage
      of DRG explant is scientifically advantageous compared to simplistic single cells
      models for multiple reasons. For instance, as an organotypic culture, the DRG
      explant allows ex vivo transfer of an entire neuronal network including the
      extracellular microenvironment that play a significant role in all the neuronal
      and glial functions. Further, DRG explants can also be maintained ex vivo for
      several days and the culture conditions can be perturbed as desired. In addition,
      the harvested DRG can be further dissociated into an in vitro co-culture of
      primary sensory neurons and satellite glial cells to investigate neuronal-glial
      interaction, neuritogenesis, axonal cone interaction with the extracellular
      microenvironment, and more general, any aspect associated with the neuronal
      metabolism. Therefore, the DRG-explant system offers a great deal of flexibility
      to study a wide array of events related to biological, physiological, and
      pathological conditions in a cost-effective manner.

PMID- 29578528
TI  - Preparation of DMMTAV and DMDTAV Using DMAV for Environmental Applications:
      Synthesis, Purification, and Confirmation.
AB  - Dimethylated thioarsenicals such as dimethylmonothioarsinic acid (DMMTAV) and
      dimethyldithioarsinic acid (DMDTAV), which are produced by the metabolic pathway
      of dimethylarsinic acid (DMAV) thiolation, have been recently found in the
      environment as well as human organs. DMMTAV and DMDTAV can be quantified to
      determine the ecological effects of dimethylated thioarsenicals and their
      stability in environmental media. The synthesis method for these compounds is
      unstandardized, making replicating previous studies challenging. Furthermore,
      there is a lack of information about storage techniques, including storage of
      compounds without species transformation. Moreover, because only limited
      information about synthesis methods is available, there may be experimental
      difficulties in synthesizing standard chemicals and performing quantitative
      analysis. The protocol presented herein provides a practically modified synthesis
      method for the dimethylated thioarsenicals, DMMTAV and DMDTAV, and will help in
      the quantification of species separation analysis using high performance liquid
      chromatography in conjunction with inductively coupled plasma mass spectrometry
      (HPLC-ICP-MS). The experimental steps of this procedure were modified by focusing
      on the preparation of chemical reagents, filtration methods, and storage.

PMID- 29578529
TI  - Moving Upwards: A Simple and Flexible In Vitro Three-dimensional Invasion Assay
      Protocol.
AB  - Although 3D invasion assays have been developed, the challenge remains to study
      cells without affecting the integrity of their microenvironment. Traditional 3D
      assays such as the Boyden Chamber require that cells are displaced from the
      original culture location and moved to a new environment. Not only does this
      disrupt the cellular processes that are intrinsic to the microenvironment, but it
      often results in a loss of cells. These problems are especially challenging when
      dealing with cells that are either rare, or extremely sensitive to their
      microenvironment. Here, we describe the development of a 3D invasion assay that
      avoids both concerns. In this assay, cells are plated within a small well and an
      ECM matrix containing a chemoattractant is laid atop the cells. This requires no
      cell displacement, and allows the cells to invade upwards into the matrix. In
      this assay, cell invasion as well as cell morphology can be assessed within the
      collagen gel. Using this assay, we characterize the invasive capacity of rare and
      sensitive cells; the hybrid cells resulting from fusion between breast cancer
      cells MCF7 and mesenchymal/multipotent stem/stroma cells (MSCs).

PMID- 29578530
TI  - The Lrp of Mycobacterium tuberculosis regulates the innate immune response of
      macrophages.

PMID- 29578531
TI  - Autophagy in dendritic cells.
AB  - Autophagy and immunity share the property of being auto-protective for the
      organism. Autophagy is an important degradation pathway that buffers nutrient
      deprivation by recycling macromolecules in organisms from yeast to man.
      Perturbations in autophagy are associated with inflammation and cancer
      development. Emerging studies have characterized the molecular details regarding
      how autophagy is controlled by immune cells. Among these, dendritic cells (DCs)
      are one of the most potent professional antigen-presenting cells critical for the
      activation of naive T cells to maintain immune tolerance and drive protective
      immunity to infection and cancer. DCs undergo functional maturation that can
      either lead to an immunostimulatory phenotype, as in the context of infection, or
      to a tolerogenic phenotype associated with immunosuppression to self-antigens, as
      well as to cancer. An increasing number of recent studies has characterized the
      involvement of autophagy in DC functions in various physiological and
      pathological contexts. Here, we provide a comprehensive review of these outcomes
      and discuss the limitation of the models used and the forefront of the knowledge
      concerning the crosstalk between autophagy and DC biology.

PMID- 29578532
TI  - Critical role of OX40 signaling in the TCR-independent phase of human and murine
      thymic Treg generation.
AB  - Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of
      Treg function can lead to the development of autoimmunity. Natural Tregs
      generated in the thymus substantially contribute to the Treg pool in the
      periphery, where they suppress self-reactive effector T cells (Teff) responses.
      Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation
      of peripheral Tregs independent of canonical antigen presentation (CAP
      independent) in the presence of low-dose IL-2. Therefore, we hypothesized that
      OX40 signaling might be integral to the TCR-independent phase of murine and human
      thymic Treg (tTreg) development. Development of tTregs is a two-step process:
      Strong T-cell receptor (TCR) signals in combination with co-signals from the
      TNFRSF members facilitate tTreg precursor selection, followed by a TCR
      independent phase of tTreg development in which their maturation is driven by IL
      2. Therefore, we investigated whether OX40 signaling could also play a critical
      role in the TCR-independent phase of tTreg development. OX40-/- mice had
      significantly reduced numbers of CD25-Foxp3low tTreg precursors and CD25+Foxp3+
      mature tTregs, while OX40L treatment of WT mice induced significant proliferation
      of these cell subsets. Relative to tTeff cells, OX40 was expressed at higher
      levels in both murine and human tTreg precursors and mature tTregs. In ex vivo
      cultures, OX40L increased tTreg maturation and induced CAP-independent
      proliferation of both murine and human tTregs, which was mediated through the
      activation of AKT-mTOR signaling. These novel findings show an evolutionarily
      conserved role for OX40 signaling in tTreg development and proliferation, and
      might enable the development of novel strategies to increase Tregs and suppress
      autoimmunity.Cellular and Molecular Immunology advance online publication, 26
      March 2018; doi:10.1038/cmi.2018.8.

PMID- 29578533
TI  - MicroRNA-663 induces immune dysregulation by inhibiting TGF-beta1 production in
      bone marrow-derived mesenchymal stem cells in patients with systemic lupus
      erythematosus.
AB  - Mesenchymal stem cells (MSCs) are critical for immune regulation. Although
      several microRNAs (miRNAs) have been shown to participate in autoimmune
      pathogenesis by affecting lymphocyte development and function, the roles of
      miRNAs in MSC dysfunction in autoimmune diseases remain unclear. Here, we show
      that patients with systemic lupus erythematosus (SLE) display a unique miRNA
      signature in bone marrow-derived MSCs (BMSCs) compared with normal controls,
      among which miR-663 is closely associated with SLE disease activity. MiR-663
      inhibits the proliferation and migration of BMSCs and impairs BMSC-mediated
      downregulation of follicular T helper (Tfh) cells and upregulation of regulatory
      T (Treg) cells by targeting transforming growth factor beta1 (TGF-beta1). MiR-663
      overexpression weakens the therapeutic effect of BMSCs, while miR-663 inhibition
      improves the remission of lupus disease in MRL/lpr mice. Thus, miR-663 is a key
      mediator of SLE BMSC regulation and may serve as a new therapeutic target for the
      treatment of lupus.Cellular and Molecular Immunology advance online publication,
      26 March 2018; doi:10.1038/cmi.2018.1.

PMID- 29578534
TI  - Chemokines: the past, the present and the future.

PMID- 29578535
TI  - NAMD goes quantum: an integrative suite for hybrid simulations.
AB  - Hybrid methods that combine quantum mechanics (QM) and molecular mechanics (MM)
      can be applied to studies of reaction mechanisms in locations ranging from active
      sites of small enzymes to multiple sites in large bioenergetic complexes. By
      combining the widely used molecular dynamics and visualization programs NAMD and
      VMD with the quantum chemistry packages ORCA and MOPAC, we created an integrated,
      comprehensive, customizable, and easy-to-use suite
      (http://www.ks.uiuc.edu/Research/qmmm). Through the QwikMD interface, setup,
      execution, visualization, and analysis are streamlined for all levels of
      expertise.

PMID- 29578536
TI  - Burden-driven feedback control of gene expression.
AB  - Cells use feedback regulation to ensure robust growth despite fluctuating demands
      for resources and differing environmental conditions. However, the expression of
      foreign proteins from engineered constructs is an unnatural burden that cells are
      not adapted for. Here we combined RNA-seq with an in vivo assay to identify the
      major transcriptional changes that occur in Escherichia coli when inducible
      synthetic constructs are expressed. We observed that native promoters related to
      the heat-shock response activated expression rapidly in response to synthetic
      expression, regardless of the construct. Using these promoters, we built a dCas9
      based feedback-regulation system that automatically adjusts the expression of a
      synthetic construct in response to burden. Cells equipped with this general-use
      controller maintained their capacity for native gene expression to ensure robust
      growth and thus outperformed unregulated cells in terms of protein yield in batch
      production. This engineered feedback is to our knowledge the first example of a
      universal, burden-based biomolecular control system and is modular, tunable and
      portable.

PMID- 29578537
TI  - Photoactivatable drugs for nicotinic optopharmacology.
AB  - Photoactivatable pharmacological agents have revolutionized neuroscience, but the
      palette of available compounds is limited. We describe a general method for
      caging tertiary amines by using a stable quaternary ammonium linkage that elicits
      a red shift in the activation wavelength. We prepared a photoactivatable nicotine
      (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study
      nicotinic acetylcholine receptors (nAChRs) in different experimental preparations
      and spatiotemporal scales.

PMID- 29578540
TI  - Retracted: Subclinical Hypothyroidism and Its Association with Increased
      Cardiovascular Mortality.
AB  - [This retracts the article DOI: 10.1155/2017/7539735.].

PMID- 29578538
TI  - Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly
      effective therapeutic strategy in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer
      diagnosed in more than 200,000 women each year and is recalcitrant to targeted
      therapies. Although TNBCs harbor multiple hyperactive receptor tyrosine kinases
      (RTKs), RTK inhibitors have been largely ineffective in TNBC patients thus far.
      We developed a broadly effective therapeutic strategy for TNBC that is based on
      combined inhibition of receptors that share the negative regulator PTPN12.
      Previously, we and others identified the tyrosine phosphatase PTPN12 as a tumor
      suppressor that is frequently inactivated in TNBC. PTPN12 restrains several RTKs,
      suggesting that PTPN12 deficiency leads to aberrant activation of multiple RTKs
      and a co-dependency on these receptors. This in turn leads to the therapeutic
      hypothesis that PTPN12-deficient TNBCs may be responsive to combined RTK
      inhibition. However, the repertoire of RTKs that are restrained by PTPN12 in
      human cells has not been systematically explored. By methodically identifying the
      suite of RTK substrates (MET, PDGFRbeta, EGFR, and others) inhibited by PTPN12,
      we rationalized a combination RTK-inhibitor therapy that induced potent tumor
      regression across heterogeneous models of TNBC. Orthogonal approaches revealed
      that PTPN12 was recruited to and inhibited these receptors after ligand
      stimulation, thereby serving as a feedback mechanism to limit receptor signaling.
      Cancer-associated mutation of PTPN12 or reduced PTPN12 protein levels diminished
      this feedback mechanism, leading to aberrant activity of these receptors.
      Restoring PTPN12 protein levels restrained signaling from RTKs, including
      PDGFRbeta and MET, and impaired TNBC survival. In contrast with single agents,
      combined inhibitors targeting the PDGFRbeta and MET receptors induced the
      apoptosis in TNBC cells in vitro and in vivo. This therapeutic strategy resulted
      in tumor regressions in chemo-refractory patient-derived TNBC models. Notably,
      response correlated with PTPN12 deficiency, suggesting that impaired receptor
      feedback may establish a combined addiction to these proto-oncogenic receptors.
      Taken together, our data provide a rationale for combining RTK inhibitors in TNBC
      and other malignancies that lack receptor-activating mutations.

PMID- 29578539
TI  - Targeting hepatic glutaminase activity to ameliorate hyperglycemia.
AB  - Glucagon levels increase under homeostatic, fasting conditions, promoting the
      release of glucose from the liver by accelerating the breakdown of glycogen (also
      known as glycogenolysis). Glucagon also enhances gluconeogenic flux, including
      from an increase in the hepatic consumption of amino acids. In type 2 diabetes,
      dysregulated glucagon signaling contributes to the elevated hepatic glucose
      output and fasting hyperglycemia that occur in this condition. Yet, the mechanism
      by which glucagon stimulates gluconeogenesis remains incompletely understood.
      Contrary to the prevailing belief that glucagon acts primarily on cytoplasmic and
      nuclear targets, we find glucagon-dependent stimulation of mitochondrial
      anaplerotic flux from glutamine that increases the contribution of this amino
      acid to the carbons of glucose generated during gluconeogenesis. This enhanced
      glucose production is dependent on protein kinase A (PKA) and is associated with
      glucagon-stimulated calcium release from the endoplasmic reticulum, activation of
      mitochondrial alpha-ketoglutarate dehydrogenase, and increased glutaminolysis.
      Mice with reduced levels of hepatic glutaminase 2 (GLS2), the enzyme that
      catalyzes the first step in glutamine metabolism, show lower glucagon-stimulated
      glutamine-to-glucose flux in vivo, and GLS2 knockout results in higher fasting
      plasma glucagon and glutamine levels with lower fasting blood glucose levels in
      insulin-resistant conditions. As found in genome-wide association studies (GWAS),
      human genetic variation in the region of GLS2 is associated with higher fasting
      plasma glucose; here we show in human cryopreserved primary hepatocytes in vitro
      that these natural gain-of-function missense mutations in GLS2 result in higher
      glutaminolysis and glucose production. These data emphasize the importance of
      gluconeogenesis from glutamine, particularly in pathological states of increased
      glucagon signaling, while suggesting a possible new therapeutic avenue to treat
      hyperglycemia.

PMID- 29578541
TI  - Perspectives on narrative medicine.

PMID- 29578543
TI  - Correction.
AB  - [This corrects the article on p. 279 in vol. 47, PMID: 29109897.].

PMID- 29578542
TI  - A Tailorable In-Situ Light-Activated Biodegradable Vascular Scaffold.
AB  - Biodegradable vascular scaffolds (BVS) are novel treatments for obstructive
      atherosclerotic cardiovascular disease that have been developed to overcome the
      limitations of traditional metallic drug-eluting stents (DES). The mechanical
      properties of bioabsorbable polymers used for the production of novel BVS are a
      key consideration for the clinical translation of this emerging technology.
      Herein, we describe the engineering of an in situ light-activated vascular
      scaffold (ILVS) comprised of a biodegradable citric acid-based elastomeric
      polymer, referred to as methacrylated poly-diol citrate (mPDC), and a
      diazeniumdiolate chitosan nitric oxide donor (chitoNO). In vitro studies
      demonstrate that the mechanical properties of the ILVS can be tailored to meet or
      exceed those of commercially available self-expanding bare metal stents (BMS).
      The radial compression strength of the ILVS is higher than that of a BMS despite
      undergoing degradation at physiologic conditions for 7 months. ILVS containing
      chitoNO provides sustained supraphysiologic levels of NO release. Lastly, ILVS
      were successfully cast in porcine arteries ex vivo using a custom designed triple
      balloon catheter, demonstrating translational potential. In conclusion, these
      data demonstrate the ability of an ILVS to provide tunable mechanical properties
      and drug-delivery capabilities for the vasculature, and thereby support mPDC as a
      promising material for the development of novel BVS platforms.

PMID- 29578545
TI  - CORRIGENDUM FOR "Eating Patterns and Health Outcomes in Patients With Type 2
      Diabetes".
AB  - [This corrects the article DOI: 10.1210/js.2017-00349.][This corrects the article
      DOI: 10.1210/js.2017-00349.].

PMID- 29578544
TI  - The orange spotted cockroach (Blaptica dubia, Serville 1839) is a permissive
      experimental host for Francisella tularensis.
AB  - Francisella tularensis is a zoonotic bacterial pathogen that causes severe
      disease in a wide range of host animals, including humans. Well-developed murine
      models of F. tularensis pathogenesis are available, but they do not meet the
      needs of all investigators. However, researchers are increasingly turning to
      insect host systems as a cost-effective alternative that allows greater increased
      experimental throughput without the regulatory requirements associated with the
      use of mammals in biomedical research. Unfortunately, the utility of previously
      described insect hosts is limited because of temperature restriction, short
      lifespans, and concerns about the immunological status of insects mass-produced
      for other purposes. Here, we present a novel host species, the orange spotted
      (OS) cockroach (Blaptica dubia), that overcomes these limitations and is readily
      infected by F. tularensis. Intrahemocoel inoculation was accomplished using
      standard laboratory equipment and lethality was directly proportional to the
      number of bacteria injected. Progression of infection differed in insects housed
      at low and high temperatures and F. tularensis mutants lacking key virulence
      components were attenuated in OS cockroaches. Finally, antibiotics were delivered
      to infected OS cockroaches by systemic injection and controlled feeding; in the
      latter case, protection correlated with oral bioavailability in mammals.
      Collectively, these results demonstrate that this new host system provides
      investigators with a new tool capable of interrogating F. tularensis virulence
      and immune evasion in situations where mammalian models are not available or
      appropriate, such as undirected screens of large mutant libraries.

PMID- 29578546
TI  - Revisiting random walk based sampling in networks: evasion of burn-in period and
      frequent regenerations.
AB  - Background: In the framework of network sampling, random walk (RW) based
      estimation techniques provide many pragmatic solutions while uncovering the
      unknown network as little as possible. Despite several theoretical advances in
      this area, RW based sampling techniques usually make a strong assumption that the
      samples are in stationary regime, and hence are impelled to leave out the samples
      collected during the burn-in period. Methods: This work proposes two sampling
      schemes without burn-in time constraint to estimate the average of an arbitrary
      function defined on the network nodes, for example, the average age of users in a
      social network. The central idea of the algorithms lies in exploiting
      regeneration of RWs at revisits to an aggregated super-node or to a set of nodes,
      and in strategies to enhance the frequency of such regenerations either by
      contracting the graph or by making the hitting set larger. Our first algorithm,
      which is based on reinforcement learning (RL), uses stochastic approximation to
      derive an estimator. This method can be seen as intermediate between purely
      stochastic Markov chain Monte Carlo iterations and deterministic relative value
      iterations. The second algorithm, which we call the Ratio with Tours (RT)
      estimator, is a modified form of respondent-driven sampling (RDS) that
      accommodates the idea of regeneration. Results: We study the methods via
      simulations on real networks. We observe that the trajectories of RL-estimator
      are much more stable than those of standard random walk based estimation
      procedures, and its error performance is comparable to that of respondent-driven
      sampling (RDS) which has a smaller asymptotic variance than many other
      estimators. Simulation studies also show that the mean squared error of RT
      estimator decays much faster than that of RDS with time. Conclusion: The newly
      developed RW based estimators (RL- and RT-estimators) allow to avoid burn-in
      period, provide better control of stability along the sample path, and overall
      reduce the estimation time. Our estimators can be applied in social and complex
      networks.

PMID- 29578547
TI  - Response to: An Aberrant Abductor Digiti Minimi Muscle Crossing the Guyon's Canal
      with Intermittent Compression of Nerve: Crucial Diagnostic Role of Nerve and
      Muscle Ultrasound.

PMID- 29578548
TI  - Orientation Uncertainty Characteristics of Some Pose Measuring Systems.
AB  - We investigate the performance of pose measuring systems which determine an
      object's pose from measurement of a few fiducial markers attached to the object.
      Such systems use point-based, rigid body registration to get the orientation
      matrix. Uncertainty in the fiducials' measurement propagates to the uncertainty
      of the orientation matrix. This orientation uncertainty then propagates to points
      on the object's surface. This propagation is anisotropic, and the direction along
      which the uncertainty is the smallest is determined by the eigenvector associated
      with the largest eigenvalue of the orientation data's covariance matrix. This
      eigenvector in the coordinate frame defined by the fiducials remains almost fixed
      for any rotation of the object. However, the remaining two eigenvectors vary
      widely and the direction along which the propagated uncertainty is the largest
      cannot be determined from the object's pose. Conditions that result in such a
      behavior and practical consequences of it are presented.

PMID- 29578549
TI  - Patient Perceptions of Readmission Risk: An Exploratory Survey.
AB  - Interventions to prevent readmissions often rely upon patient participation to be
      successful. We surveyed 895 general medicine patients slated for hospital
      discharge to (1) assess patient attitudes surrounding readmission, (2) ascertain
      whether these attitudes were associated with actual readmission, and (3)
      determine whether patients can estimate their own readmission risk. Actual
      readmissions and other clinical variables were captured from administrative data
      and linked to individual survey responses. We found that actual readmissions were
      not correlated with patients' interest in preventing readmission, sense of
      control over readmission, or intent to follow discharge instructions. However,
      patients were able to predict their own readmissions (P = .005) even after
      adjusting for predicted readmission rate, race, sex, age, and payer.
      Reassuringly, over 80% of respondents reported that they would be frustrated or
      disappointed to be readmitted and almost 90% indicated that they planned to
      follow all of their discharge instructions. Whether assessing patient-perceived
      readmission risk might help to target preventive interventions warrants further
      study.

PMID- 29578550
TI  - Training Residents in Hospital Medicine: The Hospitalist Elective National
      Survey.
AB  - As the field of hospital medicine expands, internal medicine residency programs
      can play a role in preparing future hospitalists. To date, little is known of the
      prevalence and characteristics of hospitalist-focused resident rotations. We
      surveyed the largest 100 Internal Medicine Residency Programs to better
      understand the prevalence, objectives, and structure of hospitalist-focused
      rotations in the United States. Residency leaders from 82 programs responded
      (82%). The prevalence of hospitalist-focused rotations was 50% (41/82) with an
      additional 9 programs (11%) planning to start one. Of these 41 rotations, 85%
      were elective rotations and 15% were mandatory rotations. Rotations involved
      clinical responsibilities, and most programs incorporated nonclinical curricular
      activities such as teaching, research, and work on quality improvement and
      patient safety. Respondents noted that their programs promoted autonomy,
      mentorship, and "real-world" hospitalist experience. Hospitalist-focused
      rotations may supplement traditional inpatient rotations and teach skills that
      facilitate the transition from residency to a career in hospital medicine.

PMID- 29578551
TI  - The Influence of Hospitalist Continuity on the Likelihood of Patient Discharge in
      General Medicine Patients.
AB  - Hospitalists responsible for specific inpatients may change during their
      hospitalization. To measure the association of hospitalist continuity with the
      adjusted daily discharge probability, 6,405 admissions (38,967 patientdays, 5,208
      patients) to a general medicine service at a tertiary care teaching hospital in
      2015 were investigated. Continuity was measured as the consecutive number of days
      including weekends-a hospitalist treated a particular team of patients. After
      accounting for important covariables, discharge probability increased
      significantly with hospitalist continuity; the adjusted daily discharge
      probabilities for an average patient with a new physician vs. one on service for
      4 continuous weeks were 18.1% and 25.7%, respectively (P < .001). Hospitalist
      continuity did not influence hospital mortality. Increasing hospitalist
      continuity could decrease hospital length of stay.

PMID- 29578552
TI  - Focusing on Inattention: The Diagnostic Accuracy of Brief Measures of Inattention
      for Detecting Delirium.
AB  - BACKGROUND: Delirium is frequently missed in most clinical settings. Brief
      delirium assessments are needed. OBJECTIVE: To determine the diagnostic accuracy
      of reciting the months of year backwards (MOTYB) from December to July (MOTYB-6)
      and December to January (MOTYB-12) for delirium as diagnosed by a psychiatrist
      and to explore the diagnostic accuracies of the following other brief attention
      tasks: (1) spell the word "LUNCH" backwards, (2) recite the days of the week
      backwards, (3) 10-letter vigilance "A" task, and (4) 5 picture recognition task.
      DESIGN: Preplanned secondary analysis of a prospective observational study.
      SETTING: Emergency department located within an academic, tertiary care hospital.
      PARTICIPANTS: 234 acutely ill patients who were =65 years old. MEASUREMENTS: The
      inattention tasks were administered by a physician. The reference standard for
      delirium was a comprehensive psychiatrist assessment using Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria.
      Sensitivities and specificities were calculated. RESULTS: Making any error on the
      MOTYB-6 task had a sensitivity of 80.0% (95% confidence interval [CI], 60.9%
      91.1%) and specificity of 57.1% (95% CI, 50.4%- 63.7%). Making any error on the
      MOTYB-12 task had a sensitivity of 84.0% (95% CI, 65.4%-93.6%) and specificity of
      51.9% (95% CI, 45.2%-58.5%). The best combination of sensitivity and specificity
      was reciting the days of the week backwards task; if the patient made any error,
      this was 84.0% (95% CI, 65.4%-93.6%) sensitive and 81.9% (95% CI, 76.1%-86.5%)
      specific. CONCLUSIONS: MOTYB-6 and MOTYB-12 had very good sensitivities but had
      modest specificities for delirium, limiting their use as a standalone assessment.
      Reciting the days of the week backwards appeared to have the best combination of
      sensitivity and specificity for delirium.

PMID- 29578554
TI  - It Is What It Is... For Now.

PMID- 29578553
TI  - Trends in Inpatient Admission Comorbidity and Electronic Health Data:
      Implications for Resident Workload Intensity.
AB  - In the era of duty hour regulations, there is increasing concern regarding
      resident workload compression. We conducted a retrospective, observational
      assessment of all internal medicine resident admissions to a Veterans Affairs
      hospital over a 15-year period to evaluate several admission components that
      impact resident workload and workload intensity, including electronic health
      record (EHR) data burden and patient comorbidity. A total of 67,346 admissions
      were included in the analysis. Mean patient comorbidity, as measured by the
      Charlson Comorbidity Index, increased throughout the study period. EHR data
      burden, measured by numbers of notes, medications, and discharge summaries
      available per patient at the time of admission, also increased over the study
      period. These findings suggest that EHR data burden and comorbidity have
      increased over time, which impacts resident workload in the era of duty hour
      restrictions.

PMID- 29578555
TI  - Multifunctional trastuzumab-chlorin e6 conjugate for the treatment of HER2
      positive human breast cancer.
AB  - Effective penetration and targeted delivery of anticancer drugs into tumor
      tissues are limiting factors for achieving enhanced therapeutic efficacy. In
      order to overcome the disadvantages of antibody therapy (limited penetration
      efficacy into tumor tissues) and photodynamic therapy (low targeting efficiency)
      on the treatment of HER2-positive human breast cancer simultaneously, an antibody
      and photosensitizer combined Trastuzumab-chlorin e6 conjugate (TMPC) was
      synthesized. TMPC exhibits high singlet oxygen generation under laser
      irradiation. In vitro data show that TMPC has specific HER2 selective
      interactions, and ROS generation ability upon laser irradiation induces
      significant cell death in HER2-positive breast cancer cells. The enhanced tissue
      penetration ability and tissue access of TMPC resulting from local tissue
      destruction by ROS generated from Ce6 is also demonstrated in breast cancer
      tissue blocks. The enhanced ability of TMPC is supported by in vivo fluorescence
      images of SK-BR-3 (HER2-positive cancer cells) tumor-bearing mice. The in vivo
      test demonstrates approximately 6-fold enhanced accumulation of TMPC in xenograft
      tumors with a longer retention time compared to that of the PEG-Ce6 conjugate at
      24 h. Thus, trastuzumab and photosensitizer conjugation brings synergistic
      effects for HER2 selective targeting, where TMPC enhanced tumor tissue
      penetration improves tumor tissue access and responsiveness of trastuzumab in
      HER2 overexpressing breast cancer.

PMID- 29578560
TI  - One-step synthesis of hollow C-NiCo2S4 nanostructures for high-performance
      supercapacitor electrodes.
AB  - Carbon-containing NiCo2S4 hollow-nanoflake structures were fabricated by a one
      step solvothermal method using CS2 as a single source for sulfidation and
      carbonization. The reaction mechanism for the hollow structure with carbon
      residues was explored based on the formation of a bis(dithiocarbamate)-metal
      complex and the Kirkendall effect during solvothermal synthesis. The NiCo2S4
      nanoflake electrode exhibited a high specific capacitance of 1722 F g-1 (specific
      capacity 688.8 C g-1) at a current density of 1 A g-1 and an excellent cycling
      stability (capacity retention of 98.8% after 10 000 cycles). The as-fabricated
      asymmetric supercapacitor based on NiCo2S4 nanoflakes and activated carbon
      electrodes revealed a high energy density of 38.3 W h kg-1 and a high power
      density of 8.0 kW kg-1 with a capacitance retention of 91.5% and a coulombic
      efficiency of 95.6% after 5000 cycles, highlighting its great potential for
      practical supercapacitor applications.

PMID- 29578561
TI  - Comparing winter-time herbicide behavior and exports in urban, rural, and mixed
      use watersheds.
AB  - The presence of pesticides in streams in winter, five to six years following bans
      on their municipal use suggests that complicated transport behaviour, such as
      subsurface retention and/or accumulation of pesticides and its release during
      storms, could be important for understanding recovery time frames following bans
      or legislation that aim to reduce chemical inputs. We investigated late fall and
      winter dynamics of four herbicides in paired urban and rural watersheds in
      Toronto, Canada during rainfall and snowmelt. The range of average concentrations
      and loads of the sum of atrazine, metolachlor, 2,4-D and mecoprop overlapped in
      the two types of watersheds, with slightly higher average concentrations in the
      rural watershed. Relatively consistent herbicide concentration-discharge patterns
      (i.e. dilution) were observed in the urban sub-watersheds during rainfall, while
      concentration-discharge patterns were much more variable in the rural watershed.
      This suggests relatively uniform transport pathways across the urban sub
      watersheds, compared to the rural watershed. Concentration-discharge patterns of
      the neutral herbicides atrazine and metolachlor were similar in both watersheds
      during snowmelt, though varying discharge patterns resulted in divergent timings
      of peak concentrations. In contrast, the acidic pesticides 2,4-D and mecoprop,
      which are primarily associated with urban uses, showed much more variable
      behavior across both watersheds and merit further investigation. Overall, this
      work highlights the need to consider pesticide dynamics throughout the year in
      order to more thoroughly assess the long-term efficacy of legislation governing
      their use.

PMID- 29578563
TI  - Functionalization of MOFs via a mixed-ligand strategy: enhanced CO2 uptake by
      pore surface modification.
AB  - A new Zn(ii) metal-organic framework (MOF) [Me2NH2][Zn2(BDPP)(HTZ)].4DMF (1)
      (H4BDPP = 3,5-bis(3,5-dicarboxylphenyl)pyridine, HTZ = 1H-tetrazole) has been
      constructed under solvothermal conditions by using a mixed-ligand strategy.
      Structural analysis demonstrates that 1 is a 3D framework based on four kinds of
      secondary building units (SBUs), which presents a rare structure constructed from
      quaternary SBUs and shows an uncommon (3,3,4,6)-connected topology. In
      particular, 1 contains two shapes of 1D open channels with suitable pore sizes,
      high porosity, and a highly polar pore system decorated with uncoordinated N
      atoms and carboxylic O atoms, providing a good environment for selective
      adsorption of CO2. Inspired by the structure of 1 and reticular chemistry, 5
      amino-1H-tetrazole (ATZ) was used to replace 1H-tetrazole to enhance CO2 sorption
      capacity by pore surface modification; as a result, an amino-functionalized MOF,
      [Me2NH2][Zn2(BDPP)(ATZ)].4DMF (1-NH2) was successfully built. 1-NH2 exhibits
      multipoint interactions between the CO2 molecules and the framework, resulting in
      better CO2 uptake and selectivity for CO2 over CH4 than 1.

PMID- 29578567
TI  - An inorganic-organic hybrid supramolecular framework as a high-performance anode
      for lithium-ion batteries.
AB  - Herein, an excellent anode was achieved for a lithium-ion battery based on a
      polyoxometalate-organic framework [Ni5(OH)3(trzS)3(en)(H2O)(B-alpha-PW9O34)] for
      the first time. It can deliver a capacity of 710 mA h g-1 at 100 mA g-1 after 50
      cycles and a high capacity retention of 82.2% after 500 cycles at a high rate of
      800 mA g-1, which is supposed to be due to the unique porous characteristic and
      high chemical stability of the proposed anode. The higher capacity was ascribed
      to Ni and W of the building unit taking part in lithium storage.

PMID- 29578568
TI  - A facile modular approach to the 2D oriented assembly MOF electrode for non
      enzymatic sweat biosensors.
AB  - The preparation of ordered metal organic frameworks (MOFs) will be a critical
      process for MOF-based nanoelectrodes in the future. In this work, we develop a
      novel approach to fabricating a type of MOF electrode based on flexible amino
      functionalized graphene paper modified with 2D oriented assembly of Cu3(btc)2
      nanocubes via facile interfacial synthesis and an effective dip-coating method.
      One interesting finding is that 2D arrays of Cu3(btc)2 nanocubes at oil-water
      interfaces can be transferred on amino-functionalized graphene paper, leading to
      a densely packed monolayer of Cu3(btc)2 nanocubes with a uniform size loaded on
      the paper electrode. The electrode demonstrates a variety of excellent sensing
      performances toward sweat lactate and glucose and has been applied in a non
      enzymatic electrochemical biosensing platform for the first time. The modular
      nature of this approach to assembling MOF nanocrystals will provide new insight
      into the design of MOF-based electrodes for a wide range of applications in
      biosensing instruments, wearable electronics, and lab-on-a-chip devices.

PMID- 29578570
TI  - Strengthening rehabilitation services in Indonesia: A brief situation analysis.
AB  - People with disability (PWD) in Indonesia are often neglected by society.
      Improving their life situation towards full participation in society is crucial.
      As a health strategy, rehabilitation can improve func-tioning, quality of life
      and participation in society. However, rehabilitation services in Indonesia need
      improvement. Making a situation analysis of rehabilitation services and their
      provision in the country is a pre-requisite to taking any action towards
      improvement. This paper compiles available data related to disability and
      rehabilitation services in Indonesia, using the Rehabilitation Services
      Assessment Tool (RSAT) as a framework. Gaps in provision were analysed, resulting
      in the compilation of a list of generic recommendations to improve rehabilitation
      services in the country. Indonesia faces many challenges in rehabilitation
      services, including the health workforce and the provision of services. This
      situation analysis and list of generic recommendations may be used in further
      discussions with relevant stakeholders in the country to develop a national
      strategy to strengthen rehabilitation services.

PMID- 29578571
TI  - Optimal model-based control of non-viral siRNA delivery.
AB  - Further quantitative understanding of the biological effects and mechanisms
      involved in cellular and intracellular delivery of nucleic acid materials is
      required to produce clinical applications of gene therapy. Several modeling
      approaches have been used in this field; however, a comprehensive approach that
      integrates all the key pharmacological issues into a holistic framework that is
      applicable for in vivo conditions is still lacking. This contribution presents a
      pharmacokinetic/pharmacodynamic model-based control study of non-viral siRNA
      delivery describing the dynamics of the delivery process and takes into account
      the main multi-objective optimization issues such as efficacy and toxicity, as
      well as the effect of uncertainty in cell doubling time. The methodology
      developed in this work is used to predict the optimal dosage injection rate and
      optimal intracellular exposure of siRNAs in order to improve the pharmacological
      effects before cell division occurs. The present analysis successfully provides
      quantitative predictions of non-viral siRNA activity paving the path for further
      experimental work to probe more efficient delivery systems.

PMID- 29578572
TI  - Physiological characterization and quantitative proteomic analyses of
      metabolically engineered E. coli K4 strains with improved pathways for capsular
      polysaccharide biosynthesis.
AB  - Among capsulated bacteria, some produce polysaccharides with unique properties
      that have been shown to possess relevant industrial applications and commercial
      value. The capsular polysaccharide (CPS) produced by Escherichia coli K4 is
      similar to chondroitin sulphate, and recent efforts focused on the development of
      genetic and fermentation strategies to increase its production titers up to
      technologically attractive levels. However, the control of the metabolic pathways
      leading to CPS synthesis together with the effect of varying the concentration of
      pathway intermediates on CPS final titers, is still quite unexplored, and not
      fully understood. In the present study four genes involved in the biosynthesis of
      UDP-sugar CPS precursors, namely kfoA, kfoF, pgm, and galU, were overexpressed in
      different combinations, and diversely affected the biosynthetic machinery. At the
      physiological level, results revealed a central role for kfoF, coding for UDP
      glucose dehydrogenase, that increased CPS production mostly. In the attempt to
      unravel the molecular mechanisms regulating CPS biosynthesis, an in depth
      analysis of the proteome of the recombinant strains overexpressing respectively
      pgm and galU, and pgm, galU, and kfoF was performed and compared to the wild
      type. Although, interestingly, in both strains the impact of the genetic
      manipulation seemed rather limited at the proteome level, results obtained from
      the triple mutant indicated a crosstalk between the two pathways leading to UDP
      sugar precursors biosynthesis, and also an unexpected link with the purine
      biosynthetic pathway. Overall our results present new insights into the role of
      metabolic intermediates for the formation of capsular polysaccharides, utilizing
      a systematic approach of metabolic engineering, combined with state-of-the-art
      quantitative proteomic approaches, as well as genetic and physiological
      information.

PMID- 29578573
TI  - Hollow microcarriers for large-scale expansion of anchorage-dependent cells in a
      stirred bioreactor.
AB  - With recent advances in biotechnology, mammalian cells are used in
      biopharmaceutical industries to produce valuable protein therapeutics and
      investigated as effective therapeutic agents to permanently degenerative diseases
      in cell based therapy. In these exciting and actively expanding fields, a
      reliable, efficient, and affordable platform to culture mammalian cells on a
      large scale is one of the most vital necessities. To produce and maintain a very
      large population of anchorage-dependent cells, a microcarrier-based stirred tank
      bioreactor is commonly used. In this approach, the cells are exposed to harmful
      hydrodynamic shear stress in the bioreactor and the mass transfer rates of
      nutrients and gases in the bioreactor are often kept below an optimal level to
      prevent cellular damages from the shear stress. In this paper, a hollow
      microcarrier (HMC) is presented as a novel solution to protect cells from shear
      stress in stirred bioreactors, while ensuring sufficient and uniform mass
      transfer rate of gases and nutrients. HMC is a hollow microsphere and cells are
      cultured on its inner surface to be protected, while openings on the HMC provide
      sufficient exchange of media inside the HMC. As a proof of concept, we
      demonstrated the expansion of fibroblasts, NIH/3T3 and the expansion and cardiac
      differentiation of human induced pluripotent stem cells, along with detailed
      numerical analysis. We believe that the developed HMC can be a practical solution
      to enable large-scale expansion of shear-sensitive anchorage-dependent cells in
      an industrial scale with stirred bioreactors.

PMID- 29578574
TI  - Time to challenge the spurious hierarchy of systematic over narrative reviews?

PMID- 29578575
TI  - Hybrid chickadees are deficient in learning and memory.
AB  - Identifying the phenotypes underlying postzygotic reproductive isolation is
      crucial for fully understanding the evolution and maintenance of species. One
      potential postzygotic isolating barrier that has rarely been examined is learning
      and memory ability in hybrids. Learning and memory are important fitness-related
      traits, especially in scatter-hoarding species, where accurate retrieval of
      hoarded food is vital for winter survival. Here, we test the hypothesis that
      learning and memory ability can act as a postzygotic isolating barrier by
      comparing these traits among two scatter-hoarding songbird species, black-capped
      (Poecile atricapillus) and Carolina chickadees (Poecile carolinensis), and their
      naturally occurring hybrids. In an outdoor aviary setting, we find that hybrid
      chickadees perform significantly worse on an associative learning spatial task
      and are worse at solving a novel problem compared to both parental species.
      Deficiencies in learning and memory abilities could therefore contribute to
      postzygotic reproductive isolation between chickadee species. Given the
      importance of learning and memory for fitness, our results suggest that these
      traits may play an important, but as yet overlooked, role in postzygotic
      reproductive isolation.

PMID- 29578576
TI  - Characterization of a membrane-separated and a membrane-less electrobioreactor
      for bioelectrochemical syntheses.
AB  - Bioelectrochemical systems (BESs) have the potential to contribute to the energy
      revolution driven by the new bio-economy. Until recently, simple reactor designs
      with minimal process analytics have been used. In recent years, assemblies to
      host electrodes in bioreactors have been developed resulting in so-called
      "electrobioreactors." Bioreactors are scalable, well-mixed, controlled, and
      therefore widely used in biotechnology and adding an electrode extends the
      possibilities to investigate bioelectrochemical production processes in a
      standard system. In this work, two assemblies enabling a separated and non
      separated electrochemical operation, respectively, are designed and extensively
      characterized. Electrochemical losses over the electrolyte and the membrane were
      comparable to H-cells, the bioelectrochemical standard reaction system. An effect
      of the electrochemical measurements on pH measurements was observed if the
      potential is outside the range of -1,000 to +600 mV versus Ag/AgCl.
      Electrobiotechnological characterization of the two assemblies was done using
      Shewanella oneidensis as an electroactive model organism. Current production over
      time was improved by a separation of anodic and cathodic chamber by a Nafion(r)
      membrane. The developed electrobioreactor was used for a scale-up of the
      anaerobic bioelectrochemical production of organic acids and lysine from glucose
      using an engineered Corynebacterium glutamicum. Comparison to a small-scale
      custom-made electrobioreactor indicates that anodic electro-fermentation of
      lysine and organic acids might not be limited by the BES setup but by the
      biocatalysis of the cells.

PMID- 29578577
TI  - Pharmacokinetics and Tolerability of Letermovir Coadministered With Azole
      Antifungals (Posaconazole or Voriconazole) in Healthy Subjects.
AB  - Letermovir is a human cytomegalovirus terminase inhibitor for cytomegalovirus
      infection prophylaxis in hematopoietic stem cell transplant recipients.
      Posaconazole (POS), a substrate of glucuronosyltransferase and P-glycoprotein,
      and voriconazole (VRC), a substrate of CYP2C9/19, are commonly administered to
      transplant recipients. Because coadministration of these azoles with letermovir
      is expected, the effect of letermovir on exposure to these antifungals was
      investigated. Two trials were conducted in healthy female subjects 18 to 55 years
      of age. In trial 1, single-dose POS 300 mg was administered alone, followed by a
      7-day washout; then letermovir 480 mg once daily was given for 14 days with POS
      300 mg coadministered on day 14. In trial 2, on day 1 VRC 400 mg was given every
      12 hours; on days 2 and 3, VRC 200 mg was given every 12 hours, and on day 4 VRC
      200 mg. On days 5 to 8, letermovir 480 mg was given once daily. Days 9 to 12
      repeated days 1 to 4 coadministered with letermovir 480 mg once daily. In both
      trials, blood samples were collected for the assessment of the pharmacokinetic
      profiles of the antifungals, and safety was assessed. The geometric mean ratios
      (90%CIs) for POS+letermovir/POS area under the curve and peak concentration were
      0.98 (0.83, 1.17) and 1.11 (0.95, 1.29), respectively.
      Voriconazole+letermovir/VRC area under the curve and peak concentration geometric
      mean ratios were 0.56 (0.51, 0.62) and 0.61 (0.53, 0.71), respectively. All
      treatments were generally well tolerated. Letermovir did not affect POS
      pharmacokinetics to a clinically meaningful extent but decreased VRC exposure.
      These results suggest that letermovir may be a perpetrator of CYP2C9/19-mediated
      drug-drug interactions.

PMID- 29578578
TI  - Confirmatory Population Pharmacokinetic Analysis for Sirukumab, a Human
      Monoclonal Antibody Targeting Interleukin-6, in Patients With Moderately to
      Severely Active Rheumatoid Arthritis.
AB  - The population pharmacokinetics of sirukumab, a human immunoglobulin G1kappa
      monoclonal antibody against interleukin-6, were characterized in patients with
      moderately to severely active rheumatoid arthritis in 4 phase 3 studies (SIRROUND
      D, -T, -H, and -M). A total of 17 034 serum concentrations were analyzed from
      1991 rheumatoid arthritis patients who received subcutaneous administration of
      sirukumab 50 mg every 4 weeks or 100 mg every 2 weeks. A stepwise confirmatory
      population PK analysis was conducted to accommodate the staged data release and
      the sparse sampling nature of phase 3 studies and to assess the potential
      covariate influences in an unbiased and timely manner. The base model, that is, a
      1-compartment linear model with first-order absorption and first-order
      elimination, was prespecified based on prior information from a phase 2 study
      along with information about phase 3 study design. The covariate model was also
      prespecified based on pharmacological/physiological relevance and sample size.
      After the primary covariate analysis, a simplified model was produced by removing
      covariates with effect sizes <10%. The estimated apparent clearance (CL/F) and
      volume of distribution were 0.641 L/day and 16.1 L, respectively, at standard
      body weights of 70 kg. The terminal elimination half-life was approximately 17.4
      days. Sirukumab CL/F and volume of distribution increased with body weight, and
      CL/F was higher in patients with diabetic comorbidity. Simulations suggest that
      the effects of diabetic comorbidity and weight on sirukumab exposure were
      additive. To fully understand the clinical relevance including potential dose
      adjustment, current covariate findings need to be evaluated concurrently with the
      efficacy and safety data.

PMID- 29578579
TI  - Intensity modulated operating mode of the rotating gamma system.
AB  - PURPOSE: The purpose of this work was to explore two novel operation modalities
      of the rotating gamma systems (RGS) that could expand its clinical application to
      lesions in close proximity to critical organs at risk (OAR). METHODS: The
      approach taken in this study consists of two components. First, a Geant4-based
      Monte Carlo (MC) simulation toolkit is used to model the dosimetric properties of
      the RGS Vertex 360TM for the normal, intensity modulated radiosurgery (IMRS), and
      speed modulated radiosurgery (SMRS) operation modalities. Second, the RGS Vertex
      360TM at the Rotating Gamma Institute in Debrecen, Hungary is used to collect
      experimental data for the normal and IMRS operation modes. An ion chamber is used
      to record measurements of the absolute dose. The dose profiles are measured using
      Gafchromic EBT3 films positioned within a spherical water equivalent phantom.
      RESULTS: A strong dosimetric agreement between the measured and simulated dose
      profiles and penumbra was found for both the normal and IMRS operation modes for
      all collimator sizes (4, 8, 14, and 18 mm diameter). The simulated falloff and
      maximum dose regions agree better with the experimental results for the 4 and 8
      mm diameter collimators. Although the falloff regions align well in the 14 and 18
      mm collimators, the maximum dose regions have a larger difference. For the IMRS
      operation mode, the simulated and experimental dose distributions are
      ellipsoidal, where the short axis aligns with the blocked angles. Similarly, the
      simulated dose distributions for the SMRS operation mode also adopt an
      ellipsoidal shape, where the short axis aligns with the angles where the orbital
      speed is highest. For both modalities, the dose distribution is highly
      constrained with a sharper penumbra along the short axes. CONCLUSIONS: Dose
      modulation of the RGS can be achieved with the IMRS and SMRS modes. By providing
      a highly constrained dose distribution with a sharp penumbra, both modes could be
      clinically applicable for the treatment of lesions in close proximity to critical
      OARs.

PMID- 29578580
TI  - MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in
      Patients With Parkinson's Disease.
AB  - The most commonly used Parkinson's disease (PD) treatment is the replacement of
      dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and
      catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and
      regulation of dopamine availability. In our study we investigated the possible
      relation among selected single-nucleotide polymorphisms (SNPs) in the MAO-B
      (rs1799836) and COMT (rs4680) genes and the therapeutic response to levodopa (l
      dopa). A total of 162 Brazilian patients from the Pro-Parkinson service of
      Clinics Hospital of Pernambuco diagnosed with sporadic PD and treated with
      levodopa were enrolled. PD patients were stratified into 2 groups according to
      the daily levodopa dose. MAO-B and COMT SNP genotyping was conducted by
      polymerase chain reaction-restriction fragment length polymorphism. After
      multivariate analysis, we observed a significant difference between PD groups for
      the following variables: sex (P = .02), longer duration of disease (P = .02),
      longer levodopa therapy duration (P = .01), younger onset of PD (P = .01), and
      use of COMT inhibitor (P = .02). We observed that patients carrying MAO-B
      (rs1799836) A and AA genotypes and COMT (rs4680) LL genotype suffered more
      frequently from levodopa-induced-dyskinesia. In addition, we found an increased
      risk of 2.84-fold for male individuals carrying the MAO-B G allele to be treated
      with higher doses of levodopa (P = .04). We concluded that before beginning PD
      pharmacological treatment, it is important to consider the genetic variants of
      the MAO-B and COMT genes and the sex, reinforcing the evidence that sexual
      dimorphism in the genes related to dopamine metabolism might affect PD treatment.

PMID- 29578581
TI  - Truncation of the processive Cel5A of Thermotoga maritima results in soluble
      expression and several fold increase in activity.
AB  - Cel5A of Thermotoga maritima, a 37 kDa cellulase of the family GH5, was expressed
      in partially soluble state in E. coli. However, the truncated version tCel5A1,
      produced by removing ten residues from the C-terminal of Cel5A, was expressed in
      a completely soluble form. tCel5A1 showed 7.3- fold increased specific activity
      against carboxy methyl cellulose while the increase in activities against
      regenerated amorphous cellulose and Avicel were 21 and 16 fold, respectively.
      tCel5A1 is stable at 60  degrees C for more than 2 hr and it showed temperature
      and pH optima 70  degrees C and 6.0, respectively, under the assay conditions
      used. These characteristics are similar to those of the native enzyme. As
      expected, CD spectral analysis showed that C-terminal truncation has little
      effect on the secondary structure of the molecule. tCel5A1 showed higher binding
      to pretreated rice straw (84%) as compared to the native form (46%). Molecular
      modelling analysis of tCel5A1 showed that the removal of C-terminal residues
      exposed the active site residues Glu253, Trp286, and Phe292, which are located in
      the catalytic cavity close to the C-terminus. Making these residues more
      accessible to the substrate would result in increased activity. The ratio of
      10.01 between the soluble to the insoluble reducing groups produced from RAC on
      treatment with tCel5A1, and the presence of cellobiose as the major end product
      in the hydrolysate showed that tCel5A1 is a processive cellulase. Although other
      processive cellulases belonging to the family GH5, mainly of the fungal origin,
      have been reported, but tCel5A1, to our knowledge, is the first processive
      cellulase from an extreme thermophile reported so far.

PMID- 29578582
TI  - Long-term follow-up of Chagas heart disease patients receiving an implantable
      cardioverter-defibrillator for secondary prevention.
AB  - BACKGROUND: Chagas heart disease (CHD) is a dilated cardiomyopathy characterized
      by malignant ventricular arrhythmias and increased risk of sudden cardiac death
      (SCD). Much controversy exists concerning the efficacy of implantable
      cardioverter-defibrillator (ICDs) in CHD because of mixed results observed. We
      report our long-term experience with ICDs for secondary prevention in CHD, with
      the specific aim of assessing the results in groups with preserved or depressed
      global left ventricular function. METHODS: 111 patients (75 males; 60 +/- 12
      years) were followed for 1,948 +/- 1,275 days after ICD. Time to death was the
      primary outcome; LVEF <= 45% the exposure; and age, gender, and ICD therapy
      delivery the potential confounders. We used time-to-event methods and Cox
      proportional models for analysis, censoring observations at time of death or at 5
      year follow-up in survivors. RESULTS: Seventy-two percent of the patients
      presented at least one sustained ventricular arrhythmia requiring appropriate
      therapy, and only three patients received inappropriate therapy. Death occurred
      in 50 (45%) patients, with an annual mortality rate of 8.4%, mostly due to
      refractory heart failure or noncardiac causes. Unadjusted survival rates were
      significantly distinct between patients with left ventricular ejection fraction
      (LVEF) <= 45% (26 deaths), 50.5% (95% confidence interval [CI]: 36.2%-63.2%) when
      compared to patients with LVEF > 45% (10 deaths), 77.6% (95% CI: 62.3%-87.3%, P <
      0.01). After adjusting for confounders, low LVEF (hazard ratio [HR]: 5.2, 95% CI:
      2.3-11.6), age (HR: 1.04, 95% CI: 1.01-1.07), and female gender (HR: 3.97, 95%
      CI: 1.85-8.54) were independently associated with the outcome. CONCLUSIONS: ICDs
      successfully aborted life-threatening arrhythmias in CHD patients. Impaired left
      ventricular function predicted higher mortality in CHD patients with an ICD for
      secondary prevention of SCD.

PMID- 29578584
TI  - Rearrangements under confinement lead to increased binding energy of
      Synaptotagmin-1 with anionic membranes in Mg2+ and Ca2.
AB  - Synaptotagmin-1 (Syt1) is the primary calcium sensor (Ca2+ ) that mediates
      neurotransmitter release at the synapse. The tandem C2 domains (C2A and C2B) of
      Syt1 exhibit functionally critical, Ca2+ -dependent interactions with the plasma
      membrane. With the surface forces apparatus, we directly measure the binding
      energy of membrane-anchored Syt1 to an anionic membrane and find that Syt1 binds
      with ~6 kB T in EGTA, ~10 kB T in Mg2+ and ~18 kB T in Ca2+ . Molecular
      rearrangements measured during confinement are more prevalent in Ca2+ and Mg2+
      and suggest that Syt1 initially binds through C2B, then reorients the C2 domains
      into the preferred binding configuration. These results provide energetic and
      mechanistic details of the Syt1 Ca2+ -activation process in synaptic
      transmission.

PMID- 29578583
TI  - Multi-Invasion-Induced Rearrangements as a Pathway for Physiological and
      Pathological Recombination.
AB  - Cells mitigate the detrimental consequences of DNA damage on genome stability by
      attempting high fidelity repair. Homologous recombination templates DNA double
      strand break (DSB) repair on an identical or near identical donor sequence in a
      process that can in principle access the entire genome. Other physiological
      processes, such as homolog recognition and pairing during meiosis, also harness
      the HR machinery using programmed DSBs to physically link homologs and generate
      crossovers. A consequence of the homology search process by a long nucleoprotein
      filament is the formation of multi-invasions (MI), a joint molecule in which the
      damaged ssDNA has invaded more than one donor molecule. Processing of MI joint
      molecules can compromise the integrity of both donor sites and lead to their
      rearrangement. Here, two mechanisms for the generation of rearrangements as a
      pathological consequence of MI processing are detailed and the potential
      relevance for non-allelic homologous recombination discussed. Finally, it is
      proposed that MI-induced crossover formation may be a feature of physiological
      recombination.

PMID- 29578585
TI  - Clinical Pharmacokinetics of Sulfobutylether-beta-Cyclodextrin in Patients With
      Varying Degrees of Renal Impairment.
AB  - Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms
      including methicillin-resistant S aureus and fluoroquinolone-susceptible and 
      resistant Gram-negative organisms. The intravenous formulation of delafloxacin
      contains the excipient sulfobutylether-beta-cyclodextrin (SBECD), which is
      eliminated by renal filtration. This study examined the pharmacokinetics and
      safety of SBECD after single intravenous (IV) infusions in subjects with renal
      impairment. The study was an open-label, parallel-group, crossover study in
      subjects with normal renal function or mild, moderate, or severe renal
      impairment, and those with end-stage renal disease undergoing hemodialysis.
      Subjects received 300 mg delafloxacin IV or placebo IV, containing 2400 mg SBECD,
      in 2 periods separated by >=14-day washouts. SBECD total clearance decreased with
      decreasing renal function, with a corresponding increase in area under the
      concentration-time curve (AUC0-infinity ). After IV delafloxacin 300 mg
      administration, SBECD mean total clearance was 6.28 and 1.24 L/h, mean AUC0
      infinity was 387 and 2130 h.MUg/mL, and mean renal clearance was 5.36 and 1.14
      L/h in normal and severe renal subjects, respectively. Similar values were
      obtained after IV placebo administration. In subjects with end-stage renal
      disease, delafloxacin 300 mg IV produced mean SBECD AUC0-48 values of 2715 and
      7861 h.MUg/mL when dosed before and after hemodialysis, respectively. Total SBECD
      clearance exhibited linear relationships to estimated glomerular filtration rate
      and creatinine clearance. Single doses of IV delafloxacin 300 mg and IV placebo
      were well tolerated in all groups. In conclusion, decreasing renal function
      causes reduced SBECD clearance and increased exposures, but SBECD continues to
      exhibit a good safety and tolerability profile in IV formulations.

PMID- 29578586
TI  - Religion in the Hallways: Academic Performance and Psychological Distress among
      Immigrant origin Muslim Adolescents in High Schools.
AB  - Islamic norms and Islamophobia present unique challenges for Muslim adolescents
      in Western countries. For Muslim students, even "secular" public schools are not
      a religion-free space because their religious beliefs and values are central in
      their manner of living. To inquire more about these issues, an exploratory
      sequential design mixed-method study was conducted that included focus groups and
      a survey addressing the public school experiences of Muslim adolescents in a
      Midwestern state in the United States and how those experiences are related to
      their academic achievement, educational aspirations, and psychological
      adjustment. Overall, the findings characterize this study's sample as coping well
      in the school context in terms of academic achievement, high educational
      expectations, and relatively low levels of psychological distress. However, those
      who experience greater frequency and severity of hassles at school report higher
      levels of psychological distress. In particular, the frequency of hassles
      associated with representing Islam, limited English competency, relations with
      both Muslim and non-Muslim peers, and religious discrimination at school related
      to increased distress. Together, these findings suggest the importance of
      considering both individual and ecological determinants of wellbeing for Muslim
      adolescents. The findings also suggest the importance of looking more carefully
      at the sample, context, and time when the data were collected before making
      generalizations within or across cultural and/or religious groups.

PMID- 29578587
TI  - Utilizing an ecological framework to integrate social identities and
      sociopolitical analysis in psychotherapy.
AB  - This article explores how the political events from the past year have influenced
      psychotherapeutic sessions with a female adolescent who is Peruvian,
      undocumented, and initially presented with symptoms of anxiety and a history of
      trauma. Focusing on this case example and utilizing an ecological framework, this
      article explores how the social identities of the therapist and their relation to
      power and privilege impact the therapeutic interventions that were chosen and not
      chosen. Additionally, there is a review of the benefits of consultation with a
      colleague of differing social identities and how this form of consultation can
      influence a clinician's reactions to clients regarding social or political
      issues, as well as how integrating a sociopolitical analysis is a useful and
      sometimes necessary addition to the usual work of therapy.

PMID- 29578588
TI  - Electrophysiological characterization of a mitochondrial inner membrane chloride
      channel in rat brain.
AB  - Mitochondria are an essential component of cellular integrity and homeostasis,
      and their functions and pathological processes are highly dependent on
      mitochondrial ion channels. Anion channels of the inner mitochondrial membrane
      have been described by direct patch-clamp electrophysiological methods in
      mitoplasts prepared in cardiac, liver, and brown adipose tissue, but not in
      brain. Here, using acutely isolated rat brain mitoplasts, we describe the
      properties of a large conductance, voltage-gated, pH-sensitive, outwardly
      rectifying chloride channel with conductances of 98 pS and 129 pS at negative and
      positive membrane potentials, respectively. While the molecular identity of this
      chloride conductance is unknown, it is unlikely to be a CLIC channel due to
      differences in the observed electrophysiological properties.

PMID- 29578589
TI  - Utilization of oral health services network among children and adolescents with
      leukemia.
AB  - AIM: To evaluate the use of the network of oral health services by children and
      adolescents with leukemia, according to the phase of cancer treatment, type of
      dental treatment received, and access barriers. METHODS AND RESULTS: An
      exploratory cross-sectional study carried out in a referral hospital in cancer in
      northeast of Brazil, with all children and adolescents (3-16 years old) with
      leukemia who used dental services and who attended the medical consultation in
      the outpatient clinic between March and August 2016. The analysis of the medical
      records and a structured interview with caregivers were performed. The majority
      who used only the specialized network were in a single phase of cancer treatment
      (49.1%), had oral mucositis treatment (79.2%), and had a time of displacement for
      oral health services greater than 40 minutes (92.6%). In addition, dental care
      was centered in the specialized network (76.8%) and during hospitalization
      (37.7%). CONCLUSIONS: The findings suggest that the oral health care of these
      individuals is centered on tertiary care, reflecting a deficiency in
      communication between the network services, as well as the nonrecognition of the
      basic network as a caregiver source by its users. Despite this, more research is
      needed.

PMID- 29578590
TI  - Analysis of metabolic networks of Streptomyces leeuwenhoekii C34 by means of a
      genome scale model: Prediction of modifications that enhance the production of
      specialized metabolites.
AB  - The first genome scale model (GSM) for Streptomyces leeuwenhoekii C34 was
      developed to study the biosynthesis pathways of specialized metabolites and to
      find metabolic engineering targets for enhancing their production. The model,
      iVR1007, consists of 1,722 reactions, 1,463 metabolites, and 1,007 genes, it
      includes the biosynthesis pathways of chaxamycins, chaxalactins,
      desferrioxamines, ectoine, and other specialized metabolites. iVR1007 was
      validated using experimental information of growth on 166 different sources of
      carbon, nitrogen and phosphorous, showing an 83.7% accuracy. The model was used
      to predict metabolic engineering targets for enhancing the biosynthesis of
      chaxamycins and chaxalactins. Gene knockouts, such as sle03600 (L-homoserine O
      acetyltransferase), and sle39090 (trehalose-phosphate synthase), that enhance the
      production of the specialized metabolites by increasing the pool of precursors
      were identified. Using the algorithm of flux scanning based on enforced objective
      flux (FSEOF) implemented in python, 35 and 25 over-expression targets for
      increasing the production of chaxamycin A and chaxalactin A, respectively, that
      were not directly associated with their biosynthesis routes were identified.
      Nineteen over-expression targets that were common to the two specialized
      metabolites studied, like the over-expression of the acetyl carboxylase complex
      (sle47660 (accA) and any of the following genes: sle44630 (accA_1) or sle39830
      (accA_2) or sle27560 (bccA) or sle59710) were identified. The predicted knockouts
      and over-expression targets will be used to perform metabolic engineering of S.
      leeuwenhoekii C34 and obtain overproducer strains.

PMID- 29578592
TI  - Impact of a cancer education seminar on knowledge and screening intent among
      Chinese Americans: Results from a randomized, controlled, community-based trial.
AB  - BACKGROUND: Cancer is the leading cause of death for Asian Americans. The authors
      evaluated the status of cancer prevention for Chinese Americans in San Francisco,
      which has had years of cancer prevention efforts. METHODS: Through a community
      based clinic serving Chinese Americans, a randomized, controlled trial (n = 395)
      was conducted among participants who attended either a cancer prevention seminar
      or biospecimen education seminar. Changes in knowledge, attitudes, and screening
      completion/intent were measured across and between seminar groups. RESULTS:
      Participants were mostly women who had low acculturation and education levels.
      Over two-thirds to almost all participants knew about modifiable risk factors for
      cancer and that screening tests were available, including for lung cancer. The
      majority of women had already completed mammography and Papanicolaou (Pap) tests.
      Approximately one-half reported having completed colorectal cancer screening,
      prostate screening, or hepatitis B screening. Most were nonsmokers, but about one
      half "strongly agreed" that they would want a test for tobacco smoke exposure.
      After the cancer prevention seminar, significant increases within group were
      noted for knowledge (eating healthy foods, from 93.1% to 97.7% [P = .0002];
      secondhand smoke causes cancer, from 66.3% to 74.8% [P = .04]) and for screening
      completion/intent (colorectal cancer, from 58.1% to 64.5% [P = .002] cervical
      cancer, from 72.9% to 75.5% [P = .04]) and there was a trend toward an increase
      for prostate cancer (from 50.0% to 61.1%; P = .10). There was a significant
      change between groups for eating healthy foods (P = .004). CONCLUSIONS: The
      current reports documents the gains in cancer prevention among Cantonese-speaking
      Chinese Americans, fostered by academic, community, and public health efforts. A
      community-based seminar demonstrated improvement in some cancer knowledge or
      screening intent and opportunities for continued efforts. Cancer 2018;124:1622
      30. (c) 2018 American Cancer Society.

PMID- 29578591
TI  - Inhibitory effects of Danhong Injection and its major constituents on human
      cytochrome P450 enzymes in vitro.
AB  - Danhong Injection (DHI) as a Chinese patent medicine is mainly used to treat
      ischemic encephalopathy and coronary heart disease in combination with other
      chemotherapy. However, the information on DHI's potential drug interactions is
      limited. The goal of this work was to examine the potential P450-mediated
      metabolism drug interaction arising from DHI and its active components. The
      results showed that DHI inhibited CYP2C19, CYP2D6, CYP3A4, CYP2E1 and CYP2C9 with
      IC50 values of 1.26, 1.42, 1.63, 1.10 and 1.67% (v/v), respectively. Danshensu
      and rosmarinic acid inhibited CYP2E1 and CYP2C9 with IC50 values of 36.63 and
      75.76 MUm, and 34.42 and 76.89 MUm, respectively. Salvianolic acid A and B
      inhibited CYP2D6, CYP2E1 and CYP2C9 with IC50 values of 33.79, 21.64 and 31.94
      MUm, and 45.47, 13.52 and 24.15 MUm, respectively. The study provides some useful
      information for safe and effective use of DHI in clinical practice.

PMID- 29578593
TI  - High frequency of the PNPLA3 rs738409 [G] single-nucleotide polymorphism in Hmong
      individuals as a potential basis for a predisposition to chronic liver disease.
AB  - BACKGROUND: An exploratory study was performed to determine the prevalence of the
      patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs78409 [G]
      allele among the Hmong as a risk factor for nonalcoholic fatty liver disease
      (NAFLD). NAFLD/nonalcoholic steatohepatitis is the world's most common chronic
      liver disease and is expected to replace viral hepatitis as the leading cause of
      cirrhosis and potential precursor to hepatocellular carcinoma (HCC). Of all
      populations in California, the Hmong experience the highest risk of death from
      HCC and the highest prevalence of metabolic syndrome risk factors among Asians
      that predispose them to NAFLD. Here a genetic explanation was sought for the high
      rates of chronic liver disease among the Hmong. The literature pointed to the
      PNPLA3 rs738409 [G] allele as a potential genetic culprit. METHODS: Cell-free DNA
      was isolated from 26 serum samples previously collected in community settings.
      Quantitative polymerase chain reaction-based single-nucleotide polymorphism (SNP)
      genotyping was performed with a validated TaqMan SNP genotyping assay, and
      results were analyzed with TaqMan Genotyper software. RESULTS: The PNPLA3
      rs738409 [C>G] variant occurred at a frequency of 0.46 (12 of 26; 95% confidence
      interval, 0.27-0.67). This carrier rate would rank the Hmong as the third highest
      population in the 1000 Genomes Project. CONCLUSIONS: Although this small sample
      size limits the generalizability, the high frequency rates of this allele along
      with the presence of metabolic syndrome risk factors warrant further studies into
      the etiology of NAFLD among the Hmong. Cancer 2018;124:1583-9. (c) 2018 American
      Cancer Society.

PMID- 29578594
TI  - A physician-initiated intervention to increase colorectal cancer screening in
      Chinese patients.
AB  - BACKGROUND: Among Chinese American individuals, only approximately 42% of cases
      of colorectal cancer (CRC) are diagnosed at an early stage, possibly because
      these patients are less likely than non-Hispanic white individuals to undergo CRC
      screening. METHODS: Primary care physicians (PCPs) were recruited from a local
      independent practice association serving Chinese Americans and randomized into
      early-intervention and delayed-intervention groups. PCPs in the early
      intervention group received continuing medical education (CME), and their
      patients received an intervention mailer, consisting of a letter with the PCP's
      recommendation, a bilingual educational booklet, and a fecal occult blood test
      (FOBT) kit in year 1. PCPs in the delayed-intervention group received no CME, and
      their patients received the mailers in year 2. RESULTS: A total of 20 PCPs were
      assigned to the early-intervention and 22 PCPs to the delayed-intervention group.
      A total of 3120 patients of these participating PCPs who had undergone CRC
      screening that was due during the study period were included. A total of 915
      mailers were sent in year 1 and 830 mailers were sent in year 2. FOBT screening
      rates increased from 26.7% at baseline to 58.5% in year 1 in the early
      intervention group versus 19.6% at baseline to 22.2% in year 1 in the delayed
      intervention group (P<.0001). The overall effect size of the mailer intervention
      with or without CME was estimated as a difference of 26.6 percentage points (95%
      confidence interval, 22.0-31.2 percentage points) from baseline compared with
      usual care. The intervention was found to have no impact on rates of colonoscopy
      or sigmoidoscopy. CONCLUSIONS: The results of the current pilot study
      demonstrated that a mailer including educational materials and FOBT kits can
      increase CRC screening rates with or without CME for the PCPs. Cancer
      2018;124:1568-75. (c) 2018 American Cancer Society.

PMID- 29578595
TI  - Impact of a smoke-free-living educational intervention for smokers and household
      nonsmokers: A randomized trial of Chinese American pairs.
AB  - BACKGROUND: Chinese American men smoke at a high rate, which puts household
      nonsmokers at risk. The objective of this study was to evaluate the effectiveness
      of a brief-intensity versus moderate-intensity smoke-free-living educational
      intervention for household pairs. METHODS: The authors conducted a randomized
      controlled trial of Cantonese-speaking Chinese American smoker and household
      nonsmoker pairs in San Francisco, California. Pairs were randomized to moderate
      intensity or brief-intensity group sessions with their household partner. The
      moderate-intensity group received 2 group sessions, a laboratory report of their
      baseline smoke exposure, as measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL), and 3 follow-up calls over 6 months. The brief-intensity group
      received 1 group session on tobacco-cessation resources. Primary outcomes were
      biochemically validated, past-month smoking abstinence and elimination of
      nonsmoker household exposure at 12 months. RESULTS: Participant pairs (n = 203)
      were male smokers, one-half of whom did not intend to quit within 6 months, with
      mostly female spouses as household nonsmokers. Approximately three-quarters of
      nonsmokers in both groups already had smoke-free home rules. At 12 months,
      smokers in both groups had similar biochemically validated 30-day abstinence
      rates (moderate-intensity group, 0%-20.7%; brief-intensity group, 0%-20.0%; P =
      .002 over time). More smokers in the moderate-intensity group used subsequent
      cessation group classes (moderate-intensity group, 50%; brief-intensity group,
      24%; P = .004). Household nonsmokers in both groups had similar biochemically
      validated rates of no home exposure (moderate-intensity group, 24.5%-42.2%; brief
      intensity group, 24.8%-33.3%; P = .0001 over time). CONCLUSIONS: A moderate
      intensity smoke-free-living educational intervention for Chinese-speaking
      household pairs was not more effective than a brief-intensity intervention for
      smoking abstinence and elimination of household nonsmoker exposure. Abstinence
      rates were similar to those achieved with standard group counseling. Cancer
      2018;124:1590-8. (c) 2018 American Cancer Society.

PMID- 29578596
TI  - Social-cultural, traditional beliefs, and health system barriers of hepatitis B
      screening among Hmong Americans: A case study.
AB  - BACKGROUND: The incidence of liver cancer in Hmong Americans is 5 times higher
      than that of non-Hispanic whites, and there is a low hepatitis B screening rate
      (24%) among Hmong adults compared with other Asian American populations. The
      purpose of this study was to examine the Hmong's perceptions on social-cultural
      determinants, traditional health beliefs, and health care system barriers that
      influenced community-based hepatitis B screening interventions. METHODS: A
      qualitative method was used, integrating a collective case study research design.
      In-depth interviews were used to collect data from 20 Hmong adults from the
      greater Sacramento area. A pattern matching analytic technique was used to
      analyze the data. The main core elements of Culture Care Theory were used to
      capture the key themes presented by the participants. RESULTS: Protecting a
      family's reputation; fear of doctors, medical procedures, and test results; lack
      of trust in medical doctors and medical care services; and using Hmong herbal
      medicines and practicing spiritual healing were identified as social-cultural and
      traditional health belief barriers to obtaining HBV screening. Health care costs,
      perceived discrimination, lack of transportation, linguistic discordance, and
      poor quality of care were identified as barriers to accessing high-quality health
      care services and obtaining hepatitis B screening. CONCLUSION: Providers, health
      policy makers, researchers, and community-based organizations will need to work
      together to develop intervention strategies to address the social-cultural
      factors, traditional health beliefs, and health care challenges that influence
      obtaining hepatitis B screening in the Hmong community. Cancer 2018;124:1576-82.
      (c) 2018 American Cancer Society.

PMID- 29578597
TI  - Perspectives of Chinese American smoker and nonsmoker household pairs about the
      creating smokefree living together program.
AB  - BACKGROUND: Chinese men smoke at high rates, and this puts household members at
      risk for tobacco-related diseases. Culturally responsive interventions that
      provide education and support are needed to promote smokefree living and reduce
      smoke exposure, particularly for US immigrants who experience changes in
      smokefree social norms. This qualitative study examines perspectives of Chinese
      American smoker and nonsmoker household pairs in the Creating Smokefree Living
      Together program. METHODS: Four focus groups were conducted with 30 Chinese
      American participants (15 smokers and 15 nonsmokers) who, in household pairs,
      completed smokefree education interventions of either brief or moderate
      intensity. Nearly three-quarters of the smokers continued to smoke after the
      intervention at the time of focus group participation. All smokers were male, and
      most household nonsmokers were female spouses. All participants had limited
      English proficiency. Focus group meetings were recorded, and the recordings were
      translated and transcribed. Transcripts and field notes were thematically
      analyzed. RESULTS: The following themes, shared by smokers and nonsmokers across
      interventions, were identified: 1) there was a preference for dyadic and group
      interventions because of the support offered, 2) increased knowledge of the
      health harms of smoke exposure within a pair improved the nonsmoker's support for
      smokefree living, 3) learning communication strategies improved household
      relationships and assertiveness for smokefree environments, 4) biochemical
      feedback was useful but had short-term effects, and 5) project magnets provided
      cues to action. CONCLUSIONS: Involving household partners is critical to
      smokefree interventions. Simple reminders at home appear to be more powerful than
      personal biochemical feedback of smoke exposure for sustaining motivation and
      engagement in ongoing behavioral changes within the household. Cancer
      2018;124:1599-606. (c) 2018 American Cancer Society.

PMID- 29578598
TI  - The Asian American Network for Cancer Awareness, Research, and Training
      (AANCART)'s contributions toward reducing Asian American cancer health
      disparities, 2000-2017.
AB  - BACKGROUND: In 2000 and in 2 subsequent 5-year cycles, the National Cancer
      Institute funded grantees on a regional and national basis to address community
      needs for cancer awareness, research, and training. The Asian American Network
      for Cancer Awareness, Research and Training (AANCART) is fortunate to have been
      funded since 2000 to focus on mitigating cancer health disparities facing Asian
      Americans residing primarily in California and Hawaii. This article highlights
      AANCART's achievements with respect to the original specific aims and
      unanticipated outcomes in its most recent funded cycle. METHODS: Sources included
      reports to the National Cancer Institute and peer-reviewed articles as well as
      the insights of the 3 principal investigators. RESULTS: All aims of the original
      application (infrastructure, outreach, research, and training) were attained or
      exceeded. Most distinctive was the completion and publication of 8 randomized
      controlled trials to address Asian American cancer health disparities and its
      nurture of 14 new and early stage investigators who have been productive in terms
      of research career trajectories. CONCLUSIONS: AANCART is contributing to
      mitigating Asian American cancer health disparities by catalyzing academic and
      community collaborations that have resulted in linguistically specific and
      culturally tailored educational products, scientifically rigorous interventions
      addressed at cancer risk factors, and nurturing new and early stage Asian
      American cancer investigators. Cancer 2018;124:1527-34. (c) 2018 American Cancer
      Society.

PMID- 29578599
TI  - Moving toward a true depiction of tobacco behavior among Asian Indians in
      California: Prevalence and factors associated with cultural smokeless tobacco
      product use.
AB  - BACKGROUND: Asian Indians (AIs) in the United States exhibit disproportionate
      burdens of oral cancer and cardiovascular disease, which are potentially linked
      to smokeless tobacco. However, little is known about the use of cultural
      smokeless tobacco (CST) products in this population. METHODS: California Asian
      Indian Tobacco Use Survey data from 2004 (n = 1618) were used to investigate CST
      prevalence among California's AIs. CST products included paan, paan masala, and
      gutka. A multivariable logistic regression was conducted to examine factors
      (socioeconomic status, acculturation measures, and religious affiliation)
      associated with current CST use versus never use. RESULTS: The current CST
      prevalence was 13.0% (14.0% for men and 11.8% for women). In contrast, the
      prevalence of current cigarette use was 5.5% (8.7% for men and 1.9% for women),
      and the prevalence was lower for cultural smoked tobacco (0.1% for bidis and 0.5%
      for hookahs). Factors associated with CST use included the following: being male,
      being 50 years old or older, being an immigrant, speaking an AI language at home,
      having a higher level of education (adjusted odds ratio [AOR] for high
      school/some college, 2.6; 95% confidence interval [CI], 1.1-6.5; AOR for college
      degree or higher, 4.0; 95% CI, 1.7-9.5), having a higher income (AOR for $75,000
      $100,000, 2.5; 95% CI, 1.3-4.7; AOR for >=$100,000, 2.6; 95% CI, 1.4-5.0),
      identifying as non-Sikh (AOR for Hinduism, 10.0; 95% CI, 6.0-16.5; AOR for other
      faiths, 10.2; 95% CI, 5.9-17.7), and disagreeing that spiritual beliefs are the
      foundation of life (AOR, 2.1; 95% CI, 1.2-3.5). CONCLUSIONS: The current CST
      prevalence is relatively high among California's AIs in comparison with the
      prevalence of smoking, with narrower differences between sexes. The association
      with a higher socioeconomic status is contrary to typical cigarette smoking
      patterns. Acculturation and religious affiliation are important factors
      associated with current use. Health care providers and policymakers should
      consider such determinants for targeted interventions. Cancer 2018;124:1607-13.
      (c) 2018 American Cancer Society.

PMID- 29578600
TI  - Colorectal cancer beliefs, knowledge, and screening among Filipino, Hmong, and
      Korean Americans.
AB  - BACKGROUND: To the authors' knowledge, there are few studies to date regarding
      colorectal cancer (CRC) beliefs, knowledge, and screening among multiple Asian
      American populations, who are reported to have lower CRC screening rates compared
      with white individuals. The current study was performed to assess knowledge and
      beliefs regarding the causes of CRC, its prevention, and factors associated with
      CRC screening among 3 Asian American groups. METHODS: The authors conducted an in
      language survey with Filipino (Honolulu, Hawaii), Hmong (Sacramento, California),
      and Korean (Los Angeles, California) Americans aged 50 to 75 years who were
      sampled through social networks. Bivariate and multivariable analyses were
      conducted to assess factors associated with CRC screening. RESULTS: The sample of
      981 participants was 78.3% female and 73.8% reported limited proficiency in
      English. Few of the participants were aware that age (17.7%) or family history
      (36.3%) were risk factors for CRC; 6.2% believed fate caused CRC. Only 46.4% of
      participants knew that screening prevented CRC (74.3% of Filipino, 10.6% of
      Hmong, and 55.8% of Korean participants; P<.001). Approximately two-thirds of
      participants reported ever having undergone CRC screening (76.0% of Filipino,
      72.0% of Hmong, and 51.4% of Korean participants; P<.001) and 48.6% were up to
      date for screening (62.2% of Filipino, 43.8% of Hmong, and 41.4% of Korean
      participants; P<.001). Factors found to be significantly associated with ever
      screening were being Korean (compared with Filipino), having a family history of
      CRC, having health insurance or a regular source of health care, and knowing that
      a fatty diet caused CRC. Believing that fate caused CRC and that praying
      prevented it were found to be negatively associated with ever screening. Factors
      associated with being up to date for CRC screening included being born in the
      United States, having a family history of CRC, and having access to health care.
      CONCLUSIONS: Knowledge regarding the causes of CRC and its prevention among
      Filipino, Hmong, and Korean individuals is low. However, health care access, not
      knowledge or beliefs, was found to be a key determinant of CRC screening. Cancer
      2018;124:1552-9. (c) 2018 American Cancer Society.

PMID- 29578601
TI  - Time, trust, and transparency: Lessons learned from collecting blood biospecimens
      for cancer research from the Asian American community.
AB  - BACKGROUND: Biospecimens from racially diverse groups are needed to advance
      cancer research. The Asian American Cancer Education Study was developed to
      increase the number and proportion of blood biospecimen donations from Asian
      Americans for cancer research. METHODS: The authors' targeted approach included 2
      types of community engagement, in-reach (within institution to Asian American
      patients with cancer) and outreach (external to institution to the general Asian
      American community). Participants received in-language biospecimen education
      followed by the opportunity to donate blood biospecimens. Outreach participants
      donated through our community biospecimen blood drives, and in-reach participants
      consented to donating an extra tube of blood during their routine blood draws as
      a patient. Donated blood biospecimens were spun down to serum and plasma to be
      stored in a biorepository or were sent to the laboratory to test for cancer
      related risk factors. RESULTS: Three hundred eighty-eight Asian Americans donated
      1127 blood biospecimens for cancer research. Four hundred twenty tubes of plasma
      and serum are currently being stored at the cancer center's biorepository, 39
      tubes have been used for cancer genomic research, and 668 tubes were used to
      characterize cancer-related risk factors. CONCLUSIONS: Building upon the past
      decade of the National Cancer Institute-funded Asian American Network for Cancer
      Awareness, Research, and Training's foundation of trust and service among Asian
      Americans, researchers were able to leverage relationships not only to introduce
      the idea of biospecimen contribution to the community but to also exceed
      expectations with regard to the quantity of blood biospecimens collected from
      Asian Americans. Cancer 2018;124:1614-21. (c) 2018 American Cancer Society.

PMID- 29578602
TI  - Colorectal cancer screening prevalence and predictors among Asian American
      subgroups using Medical Expenditure Panel Survey National Data.
AB  - BACKGROUND: Asian American (AA) ethnic subgroups are diverse in socio-economic
      status, years in the United States, English proficiency, and cultures with
      different health seeking behaviors and health care access. Fifty-two percent of
      AAs age >=50 years had colorectal cancer screening (CRCS) in 2013, compared with
      61% of non-Hispanic whites. We hypothesized that CRCS prevalence among AA
      ethnicities is heterogeneous and that the reasons related to CRCS among AA
      subgroups are associated with demographic characteristics, acculturation, health
      care access, and health attitudes. METHODS: Medical Expenditure Panel Survey data
      for 2009-2014 compared CRCS status among whites (n = 28,834), Asian Indians (n =
      466), Chinese (n = 652), and Filipinos (n = 788). Multivariate logistic
      regression examined ethnic differences and correlates of CRCS accounting for
      complex sampling design. RESULTS: Whites had the highest prevalence of screening
      (62.3%), followed by Filipinos (55.0%), Chinese (50.9%), and Asian Indians
      (48.6%). Older age, having health insurance, and having a usual care provider
      predicted CRCS across all ethnicities. Different demographic, health care access,
      and health attitude predictors within each ethnic group were related to CRCS.
      CONCLUSION: This study contributes to the literature on influences of
      differential CRCS prevalence among AA subgroups. CRCS promotion should be
      tailored according to attitudes and structural barriers affecting screening
      behavior of specific ethnic subgroups to truly serve the health needs of the
      diverse AA population. Cancer 2018;124:1543-51. (c) 2018 American Cancer Society.

PMID- 29578603
TI  - Results of a lay health education intervention to increase colorectal cancer
      screening among Filipino Americans: A cluster randomized controlled trial.
AB  - BACKGROUND: Filipino colorectal cancer (CRC) screening rates fall below Healthy
      People 2020 goals. In this study, the authors explore whether a lay health
      educator (LHE) approach can increase CRC screening among Filipino Americans ages
      50 to 75 years in Hawai'i. METHODS: A cluster randomized controlled trial from
      2012 through 2015 compared an intervention, which consisted of LHEs delivering 2
      education sessions and 2 telephone follow-up calls on CRC screening plus a CRC
      brochure versus an attention control, in which 2 lectures and 2 follow-up calls
      on nutrition and physical activity plus a CRC brochure were provided. The primary
      outcome was change in self-reported ever receipt of CRC screening at 6 months.
      RESULTS: Among 304 participants (77% women, 86% had > 10 years of residence in
      the United States), the proportion of participants who reported ever having
      received CRC screening increased significantly in the intervention group (from
      80% to 89%; P = .0003), but not in the control group (from 73% to 74%; P = .60).
      After covariate adjustment, there was a significant intervention effect (odds
      ratio, 1.9; 95% confidence interval, 1.0-3.5). There was no intervention effect
      on up-to-date screening. CONCLUSIONS: This first randomized controlled trial for
      CRC screening among Hawai'i's Filipinos used an LHE intervention with mixed, but
      promising, results. Cancer 2018;124:1535-42. (c) 2018 American Cancer Society.

PMID- 29578604
TI  - Knowledge of colorectal cancer screening guidelines and intention to obtain
      screening among nonadherent Filipino, Hmong, and Korean Americans.
AB  - BACKGROUND: Nonadherence to colorectal cancer (CRC) screening among Asian
      Americans is high but not well understood. This study examined correlates of
      screening intention among Filipino, Hmong, and Korean Americans who were
      nonadherent to CRC screening. METHODS: Using cross-sectional, preintervention
      survey data from 504 Asian Americans (115 Filipinos, 185 Hmong, and 204 Koreans)
      aged 50-75 years who were enrolled in a multisite cluster randomized controlled
      trial of lay health educator intervention, we analyzed correlates of self
      reported CRC screening nonadherence, which was defined as not being up-to-date
      for fecal occult blood test, sigmoidoscopy, or colonoscopy. RESULTS: Only 26.8%
      of participants indicated intention to obtain screening within 6 months (Hmong:
      12.4%; Korean: 30.8%; and Filipino: 42.6%; P < .001). Only one third of
      participants had undergone a prior screening, and a majority did not know that
      screening is a method of CRC prevention method (61.3%) or had any knowledge of
      CRC screening guidelines (53.4%). Multivariable analyses revealed that patient
      provider ethnicity concordance, provider's recommendation of screening,
      participants' prior CRC screening, perceived severity and susceptibility of CRC,
      and knowledge of guidelines were positively associated with screening intention.
      Specifically, knowing one or more screening guidelines doubled the odds of
      screening intention (adjusted odds ratio, 2.38; 95% confidence interval, 1.32
      4.28). Hmong were less likely to have screening intention than Filipinos, which
      was unexplained by socio-demographics, health care factors, perceived needs for
      CRC screening, or knowledge of screening guidelines. CONCLUSION: CRC screening
      intention among nonadherent Filipino, Hmong, and Korean Americans was low.
      Targeting knowledge of CRC screening guidelines may be effective strategies for
      increasing CRC screening intention among nonadherent Asian Americans. Cancer
      2018;124:1560-7. (c) 2018 American Cancer Society.

PMID- 29578605
TI  - The influence of adherence to antipsychotics medication on the quality of life
      among patients with schizophrenia in Indonesia.
AB  - PURPOSE: Investigating factors that can predict medication adherence and quality
      of life, as well as the influence of adherence to medication on the quality of
      life among patients with schizophrenia. DESIGN AND METHODS: This study applies
      descriptive cross-sectional design. Participants were determined from outpatient
      clinic in a psychiatric hospital in Indonesia. Several questionnaires were used,
      including self-report, Glasgow Antipsychotics Side-effect Scale, drug attitude
      inventory and SQOL-18. FINDINGS: Side-effect factor (p < .05) could influence
      medication adherence. Residential area (p < .05) could significantly influence
      quality of life. There was also a correlation between medication adherence and
      quality of life (p < .05). PRACTICE IMPLICATIONS: Findings suggest to put more
      emphasis on assessing medication side effects.

PMID- 29578606
TI  - Structural and enzymatic analyses of Anabaena heterocyst-specific alkaline
      invertase InvB.
AB  - Anabaena sp. PCC 7120 encodes two alkaline/neutral invertases, namely InvA and
      InvB. Following our recently reported InvA structure, here we report the crystal
      structure of the heterocyst-specific InvB. Despite sharing an overall structure
      similar to InvA, InvB possesses a much higher catalytic activity. Structural
      comparisons of the catalytic pockets reveal that Arg430 of InvB adopts a
      different conformation, which may facilitate the deprotonation of the catalytic
      residue Glu415. We propose that the higher activity may be responsible for the
      vital role of InvB in heterocyst development and nitrogen fixation. Furthermore,
      phylogenetic analysis combined with activity assays also suggests the role of
      this highly conserved arginine in plants and cyanobacteria, as well as some
      proteobacteria living in highly extreme environments.

PMID- 29578607
TI  - Mr. Trump: How I learned to stop worrying and love the patient-aggressor.
AB  - This paper offers an integration of social issues, psychoanalytic theory, and
      analytic experience in the treatment of a patient whose political values and
      identifications differed significantly from my own. Our political leanings
      facilitated a dynamic tension of difference, power, and aggression that mirrored
      how each of us felt in relation to the current social-political milieu. In
      particular, the sadomasochistic dynamics on display in the treatment offered me a
      unique way of understanding my relationship with my patient and opened new ways
      of understanding the political present. In the end, I learned to stop worrying
      about getting rid of anger, aggression, and splitting, and instead to embrace
      what these feelings and behaviors can tell me as a therapist, and what they can
      inform for my patients about the nature of relationality, identity, and
      difference.

PMID- 29578608
TI  - Optimization of bioprocess productivity based on metabolic-genetic network models
      with bilevel dynamic programming.
AB  - One of the main goals of metabolic engineering is to obtain high levels of a
      microbial product through genetic modifications. To improve the productivity of
      such a process, the dynamic implementation of metabolic engineering strategies
      has been proven to be more beneficial compared to static genetic manipulations in
      which the gene expression is not controlled over time, by resolving the trade-off
      between growth and production. In this work, a bilevel optimization framework
      based on constraint-based models is applied to identify an optimal strategy for
      dynamic genetic and process level manipulations to increase productivity. The
      dynamic enzyme-cost flux balance analysis (deFBA) as underlying metabolic network
      model captures the network dynamics and enables the analysis of temporal
      regulation in the metabolic-genetic network. We apply our computational framework
      to maximize ethanol productivity in a batch process with Escherichia coli. The
      results highlight the importance of integrating the genetic level and enzyme
      production and degradation processes for obtaining optimal dynamic gene and
      process manipulations.

PMID- 29578609
TI  - Regional Gastrointestinal Absorption of Apixaban in Healthy Subjects.
AB  - This study was conducted to investigate the extent of absorption in different
      regions of the gastrointestinal (GI) tract. The relative bioavailability of an
      apixaban crushed tablet was also assessed to investigate the effect of
      dissolution on absorption. This was an open-label, randomized, 4-period, 4
      treatment crossover study with a 7-day washout period balanced for first-order
      residual effects in 12 healthy subjects. Subjects received a single dose of a 2.5
      mg apixaban solution administered orally, released in the distal small intestine
      and in the ascending colon. In addition, subjects received a single dose of a 2.5
      mg apixaban crushed tablet released in the ascending colon. The solution and
      crushed tablet were delivered via Enterion capsules. The location of Enterion
      capsules was monitored using scintigraphic imaging. Apixaban maximum observed
      plasma concentration (Cmax ) and area under the plasma concentration-time curve
      from zero to the time of the last quantifiable concentration (AUC0-t ) decreased
      by approximately 60% when it was delivered to the distal small bowel compared
      with the oral administration. A greater decrease was observed when it was
      delivered to the ascending colon, with reductions of 90% and 84% in Cmax and AUC0
      t , respectively. A crushed tablet delivered to the ascending colon resulted in
      exposure that was approximately 40% of that observed for solution released in the
      same region. These findings indicate that apixaban exhibits region-dependent
      absorption and that dissolution/solubility of the solid-dose form is limited in
      the ascending colon. Apixaban absorption decreased progressively along the GI
      tract, indicating that absorption occurs primarily in the upper GI tract.

PMID- 29578610
TI  - Nuclear magnetic resonance- and mass spectrometry-based metabolomics to study
      maleic acid toxicity from repeated dose exposure in rats.

PMID- 29578611
TI  - Calcium channel blockers for antipsychotic-induced tardive dyskinesia.
AB  - BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of
      any population. Antipsychotic medications are the primary treatment for these
      disorders. Antipsychotic medications are associated with a variety of adverse
      effects including tardive dyskinesia. Dyskinesia is a disfiguring movement
      disorder of the orofacial region that can be tardive (having a slow or belated
      onset). Tardive dyskinesia is difficult to treat, despite experimentation with
      several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine,
      verapamil, flunarizine) have been among these experimental treatments.
      OBJECTIVES: To determine the effects of calcium channel blocker drugs (diltiazem,
      nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive
      dyskinesia in people with schizophrenia, schizoaffective disorder or other
      chronic mental illnesses. SEARCH METHODS: We searched the Cochrane Schizophrenia
      Group Trials Register (July 2015 and April 2017), inspected references of all
      identified studies for further trials and contacted authors of trials for
      additional information. SELECTION CRITERIA: We selected randomised controlled
      trials comparing calcium channel blockers with placebo, no intervention or any
      other intervention for people with both tardive dyskinesia and schizophrenia or
      serious mental illness who remained on their antipsychotic medication. DATA
      COLLECTION AND ANALYSIS: We independently extracted data and estimated risk
      ratios of dichotomous data or mean differences (MD) of continuous data, with 95%
      confidence intervals (CI). We assumed that people who left the trials early had
      no improvement. We also created a 'Summary of findings' table using GRADE. MAIN
      RESULTS: Previous versions of this review included no trials. From the 2015
      search, we identified three cross-over trials that could be included. The 2017
      search found no new studies relevant to this review. The included trials
      randomised 47 inpatients with chronic mental illnesses in the USA and China.
      Trials were published in the 1990s and were of short duration (six to 10 weeks).
      Overall, the risk of bias was unclear, mainly due to poor reporting; allocation
      concealment was not described, generation of the sequence was not explicit,
      studies were not clearly blinded, and attrition and outcome data were not fully
      reported. Findings were sparse, no study reported on the primary outcome 'no
      clinically important improvement in tardive dyskinesia symptoms,' but two small
      studies (37 participants) found no difference on the tardive dyskinesia symptoms
      scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or
      flunarizine and placebo after three to four weeks' treatment (MD -0.71, 95% CI 
      2.68 to 1.26, very low quality evidence). Only one study randomising 20
      participants reported on adverse events, and reported that there were no adverse
      events with flunarizine or with placebo (very low quality evidence). One study
      with 18 participants reported no events of deterioration in mental state with
      diltiazem or with placebo (very low quality evidence). No studies reported on
      acceptability of treatment or on social confidence, social inclusion, social
      networks or personalised quality of life outcomes designated important to
      patients. AUTHORS' CONCLUSIONS: Available evidence from randomised controlled
      trials is extremely limited and very low quality, conclusions cannot be drawn.
      The effects of calcium channel blockers for antipsychotic-induced tardive
      dyskinesia are unknown. Their use is experimental and should only be given in the
      context of well-designed randomised trials.

PMID- 29578612
TI  - What is your diagnosis? Caudal fossa mass from a dog.

PMID- 29578613
TI  - Digital disparities and vulnerability: mobile phone use, information behaviour,
      and disaster preparedness in Southeast Asia.
AB  - This paper proposes an ecological view to investigate how disparities in mobile
      technology use reflect vulnerabilities in communities vis-a-vis disaster
      preparedness. Data (n=1,603) were collected through a multi-country survey
      conducted equally in rural and urban areas of Indonesia, Myanmar, Philippines,
      and Vietnam, where mobile technology has become a dominant and ubiquitous
      communication and information medium. The findings show that smartphone users'
      routinised use of mobile technology and their risk perception are significantly
      associated with disaster preparedness behaviour indirectly through disaster
      related information sharing. In addition to disaster-specific social support,
      smartphone users' disaster-related information repertoires are another strong
      influencing factor. In contrast, non-smartphone users are likely to rely solely
      on receipt of disaster-specific social support as the motivator of disaster
      preparedness. The results also reveal demographic and rural-urban differences in
      disaster information behaviour and preparedness. Given the increasing shift from
      basic mobile phone models to smartphones, the theoretical and policy-oriented
      implications of digital disparities and vulnerability are discussed.

PMID- 29578614
TI  - Self-assembly and chiroptical properties in supramolecular complexes of adenosine
      phosphates and guanidinium-bispyrene.
AB  - Supramolecular systems that respond to the hydrolysis of adenosine phosphates
      (APs) are attractive for biosensing and to fabricate bioinspired self-assembled
      materials. Here, we report on the formation of supramolecular complexes between
      an achiral guanidinium derivative bearing two pyrene moieties, with each of the
      three adenosine phosphates: AMP, ADP, and ATP. By combining results from circular
      dichroism spectroscopy and molecular modeling simulations, we explore the induced
      chirality, the dynamics of the complexes, and the interactions at play, which
      altogether provide insights into the supramolecular self-assembly between APs and
      the guanidinium-bispyrene. Finally, we identify the chiroptical signals of
      interest in mixtures of the guanidinium derivative with the three APs in
      different proportions. This study constitutes a basis to evolve toward a
      chiroptical detection of the hydrolysis of APs based on organic supramolecular
      probes.

PMID- 29578615
TI  - Enantioselective complexation of 1-phenylethanol with chiral compounds bearing
      urea moiety.
AB  - A detailed study of diastereomeric complexes of chiral ureido-1,1'-binaphthalene
      derivatives with chiral 1-phenylethanol showed that a derivative bearing only one
      urea unit makes five times more stable complex with (S)-enantiomer than with (R)
      enantiomer of the alcohol. This phenomenon could be used in chiral discrimination
      processes. The influence of individual parts of the structure on the complexation
      properties is shown. The probable structure of diastereomeric complexes based on
      experimental results and computational methods is proposed.

PMID- 29578616
TI  - Tauroursodeoxycholic acid produces antidepressant-like effects in a chronic
      unpredictable stress model of depression via attenuation of neuroinflammation,
      oxido-nitrosative stress, and endoplasmic reticulum stress.
AB  - Depression is a common psychiatric disorder with heavy economic and social
      burdens. Searching new agents with better antidepressant-like activities is of
      great significance for depression therapy. Tauroursodeoxycholic acid (TUDCA), a
      clinical drug for gallstone treatment, possesses neuroprotective effects in
      different brain disorders. However, whether it affects depression remains
      unclear. We addressed this issue by evaluating the effect of TUDCA on depression
      induced by chronic unpredictable stress (CUS). Results showed that TUDCA
      treatment at 200 but not 100 mg/kg prevented the 5 weeks of CUS-induced increases
      in the immobile time of C57BL6/J mice in the experiments of forced swimming test
      and tail suspension test as well as the CUS-induced decrease in sucrose intake
      and crossing numbers in the open-field test, and did not enhance the
      antidepressant-like effect of fluoxetine. Attenuation of neuroinflammation may be
      involved in the antidepressant-like effect of TUDCA, as TUDCA treatment (200
      mg/kg) normalized the levels of tumor necrosis factor-alpha and interleukin-6 in
      both hippocampus and prefrontal cortex. The increases in inflammasome and
      microglial activation markers, including interleukin-beta, nod-like receptor
      protein 3, and Iba-1, in CUS-treated mice were reduced by TUDCA treatment (200
      mg/kg). TUDCA treatment (200 mg/kg) also normalized the changes in markers
      reflecting the oxidative-nitrosative and endoplasmic reticulum (ER) stress
      induced by CUS, such as nitric oxide, reduced glutathione, malondialdehyde,
      glucose-regulated protein 78, and C/EBP homologous protein. These results
      revealed that TUDCA improved the CUS-induced depression-like behaviors likely
      through attenuation of neuroinflammation, oxido-nitrosative, and ER stress.

PMID- 29578617
TI  - Dative and Electron-Sharing Bonding in C2 F4.
AB  - The reaction pathway for the rupture of the carbon-carbon double bond of C2 F4
      has been calculated with ab initio methods at the CASSCF(8,8)+NEVPT2/aug-cc-pVTZ
      and CCSD(T)/aug-cc-pVTZ levels and with density functional theory using M06-L and
      M06-2X functionals in conjunction with aug-cc-pVTZ basis sets. The calculations
      suggest that the bond dissociation pathway proceeds by a nonlinear reaction
      course without an activation barrier yielding the CF2 fragments in the (1 A1 )
      ground state. A bonding analysis indicates that there is a continuous change in
      the electronic structure of the CF2 fragments during the elongation of the C-C
      distance from a (3 B1 ) excited state at the equilibrium geometry of C2 F4 to the
      (1 A1 ) ground state. EDA-NOCV calculations suggest that the carbon-carbon
      interactions in C2 F4 at equilibrium distance and longer C-C values up to ~1.60 A
      are best described in terms of electron-sharing bonding between the CF2 fragments
      in the (3 B1 ) excited state. At longer distances, the situation changes toward
      dative bonding between CF2 fragments in the (1 A1 ) ground state.

PMID- 29578618
TI  - High-Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal
      Women-A 3-Month Intervention Study.
AB  - Bone adapts to loading in several ways, including redistributing bone mass and
      altered geometry and microarchitecture. Because of previous methodological
      limitations, it is not known how the bone material strength is affected by
      mechanical loading in humans. The aim of this study was to investigate the effect
      of a 3-month unilateral high-impact exercise program on bone material properties
      and microarchitecture in healthy postmenopausal women. A total of 20 healthy and
      inactive postmenopausal women (aged 55.6 +/- 2.3 years [mean +/- SD]) were
      included and asked to perform an exercise program of daily one-legged jumps (with
      incremental number, from 3*10 to 4*20 jumps/d) during 3 months. All participants
      were asked to register their performed jumps in a structured daily diary. The
      participants chose one leg as the intervention leg and the other leg was used as
      control. The operators were blinded to the participant's choice of leg for
      intervention. The predefined primary outcome was change in bone material strength
      index (BMSi), measured at the mid tibia with a handheld reference probe
      indentation instrument (OsteoProbe). Bone microstructure, geometry, and density
      were measured with high-resolution peripheral quantitative computed tomography
      (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal).
      Differences were analyzed by related samples Wilcoxon signed rank test. The
      overall compliance to the jumping program was 93.6%. Relative to the control leg,
      BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no
      differences were found for any of the XtremeCT-derived bone parameters. In
      conclusion, a unilateral high-impact loading program increased BMSi in
      postmenopausal women rapidly without affecting bone microstructure, geometry, or
      density, indicating that intense mechanical loading has the ability to rapidly
      improve bone material properties before changes in bone mass or structure. (c)
      2018 The Authors. Journal of Bone and Mineral Research Published by Wiley
      Periodicals Inc.

PMID- 29578619
TI  - Transport of Nucleoside Triphosphates into Cells by Artificial Molecular
      Transporters.
AB  - Chemically modified nucleoside triphosphates (NTPs) are widely exploited as
      unnatural metabolites in chemical biology and medicinal chemistry. Because
      anionic NTPs do not permeate cell membranes, their corresponding neutral
      precursors are employed in cell-based assays. These precursors become active
      metabolites after enzymatic conversion, which often proceeds insufficiently. Here
      we show that metabolically-active NTPs can be directly transported into
      eukaryotic cells and bacteria by the action of designed synthetic nucleoside
      triphosphate transporters (SNTTs). The transporter is composed of a receptor,
      which forms a non-covalent complex with a triphosphate anion, and a cell
      penetrating agent, which translocates the complex across the plasma membrane. NTP
      is then released from the complex in the intracellular milieu and accumulates in
      nuclei and nucleoli in high concentration. The transport of NTPs proceeds rapidly
      (seconds to minutes) and selectively even in the presence of other organic
      anions. We demonstrate that this operationally simple and efficient means of
      transport of fluorescently labelled NTPs into cells can be used for metabolic
      labeling of DNA in live cells.

PMID- 29578620
TI  - Ionization of tocopherols and tocotrienols in atmospheric pressure chemical
      ionization.
AB  - RATIONALE: Tocopherols and tocotrienols are chemical compounds insusceptible to
      the ionization process under atmospheric pressure conditions. Therefore, the
      selection of the optimal ion source settings for their quantification requires
      special attention. The aim of this study was to analyse the influence of the APCI
      source parameters on the response of tocochromanols and two related compounds.
      METHODS: Standard solutions of target compounds were injected on the high
      performance liquid chromatography/atmospheric pressure chemical ionization tandem
      mass spectrometry (HPLC/APCI-MS/MS) system separately and analysed with 30
      randomly selected ion source settings. The obtained responses were modelled by
      multivariate linear regression with least absolute shrinkage and selection
      operator. The developed models were used to choose the best APCI conditions.
      RESULTS: Multivariate linear models were built for eight tocochromanols, trolox
      and BHT. The APCI settings derived from the models did not increase the peak
      areas obtained for T and T3 during the ionization process. Ionization conditions
      based on models for trolox and BHT improved analytical responses by 12-36% and 4
      32%, respectively. The application of the ion source settings optimal for trolox
      and BHT to tocochromanols did not result in better analytical responses.
      CONCLUSIONS: The ionization pattern of tocochromanols in the APCI source is
      problematic and should be further investigated. Modelling methodology for
      response improvement presented in this study can be applied in similar studies.

PMID- 29578621
TI  - Site-Selective delta-C(sp3 )-H Alkylation of Amino Acids and Peptides with
      Maleimides via a Six-Membered Palladacycle.
AB  - The site-selective functionalization of unactivated C(sp3 )-H bonds remains one
      of the greatest challenges in organic synthesis. Herein, we report on the site
      selective delta-C(sp3 )-H alkylation of amino acids and peptides with maleimides
      via a kinetically less favored six-membered palladacycle in the presence of more
      accessible gamma-C(sp3 )-H bonds. Experimental studies revealed that C-H bond
      cleavage occurs reversibly and preferentially at gamma-methyl over delta-methyl C
      H bonds while the subsequent alkylation proceeds exclusively at the six-membered
      palladacycle that is generated by delta-C-H activation. The selectivity can be
      explained by the Curtin-Hammett principle. The exceptional compatibility of this
      alkylation with various oligopeptides renders this procedure valuable for late
      stage peptide modifications. Notably, this process is also the first
      palladium(II)-catalyzed Michael-type alkylation reaction that proceeds through
      C(sp3 )-H activation.

PMID- 29578622
TI  - Dynamic Changes in the Structure, Chemical State and Catalytic Selectivity of Cu
      Nanocubes during CO2 Electroreduction: Size and Support Effects.
AB  - In situ and operando spectroscopic and microscopic methods were used to gain
      insight into the correlation between the structure, chemical state, and
      reactivity of size- and shape-controlled ligand-free Cu nanocubes during CO2
      electroreduction (CO2 RR). Dynamic changes in the morphology and composition of
      Cu cubes supported on carbon were monitored under potential control through
      electrochemical atomic force microscopy, X-ray absorption fine-structure
      spectroscopy and X-ray photoelectron spectroscopy. Under reaction conditions, the
      roughening of the nanocube surface, disappearance of the (100) facets, formation
      of pores, loss of Cu and reduction of CuOx species observed were found to lead to
      a suppression of the selectivity for multi-carbon products (i.e. C2 H4 and
      ethanol) versus CH4 . A comparison with Cu cubes supported on Cu foils revealed
      an enhanced morphological stability and persistence of CuI species under CO2 RR
      in the former samples. Both factors are held responsible for the higher C2 /C1
      product ratio observed for the Cu cubes/Cu as compared to Cu cubes/C. Our
      findings highlight the importance of the structure of the active nanocatalyst but
      also its interaction with the underlying substrate in CO2 RR selectivity.

PMID- 29578623
TI  - Spectroscopic Identification of H2 NSO and syn- and anti-HNSOH Radicals.
AB  - The simplest aminosulfinyl radical H2 NSO has been generated in the gas phase
      through flash vacuum pyrolysis of CF3 S(O)NH2 at approximately 1000 K. Upon UV
      light irradiation (365 nm), 1,3-H migration occurs in H2 NSO and furnishes an
      elusive N-amidyl radical HNSOH in syn and anti conformations in cryogenic
      matrices (N2 or Ar, 15 K). Further 266 nm laser irradiation results in
      dissociation of HNSOH to H2 O and SN and concomitant reformation of H2 NSO in
      trace amount. The identification of H2 NSO, syn-HNSOH, and anti-HNSOH by matrix
      isolation IR spectroscopy is supported by high-level quantum chemical
      computations.

PMID- 29578624
TI  - Robust Organocatalysts for the Cleavage of Vegetable Oil Derivatives to Aldehydes
      through Retrobenzoin Condensation.
AB  - A series of thiazolium salts was prepared and tested for the cleavage of the
      alpha-hydroxyketone derived from methyl oleate. The robustness of these
      precatalysts was determined by dynamic thermogravimetric analyses (TGA). It has
      been shown that the stability of these species is mainly governed by the nature
      of the counter-anion and some of them were found to be stable until 350-400 
      degrees C. The alpha-hydroxyketone derived from methyl oleate was cleaved under
      reactive distillation conditions using optimized, thermally robust N
      butylthiazolium triflate to give the cleavage product, namely, nonanal and methyl
      azelaaldehydate, with 85 and 70 % yields. A range of alpha-hydroxyketones derived
      from several fatty acids was cleaved to give the corresponding bio-based
      aldehydes with up to 98 % isolated yields. Finally, this protocol was
      successfully applied to a high-oleic sunflower oil derivative.

PMID- 29578625
TI  - Detection of titanium nanoparticles in the hair shafts of a patient with frontal
      fibrosing alopecia.

PMID- 29578627
TI  - Various cold plasma devices for the treatment of actinic keratosis.

PMID- 29578626
TI  - Both children and adult patients with difficult-to-treat atopic dermatitis have
      high prevalences of concomitant allergic contact dermatitis and are frequently
      polysensitized.
AB  - BACKGROUND: Concomitant allergic contact dermatitis (ACD) has been described as a
      possible cause of atopic dermatitis (AD) becoming difficult-to-treat. However,
      contact sensitization in this patient group has barely been studied. OBJECTIVE:
      To study the occurrence of ACD in a population of difficult-to-treat AD children
      and adults. METHODS: Clinical and patch test information of 48 patients with
      difficult-to-treat AD unresponsive to conventional outpatient treatments was
      gathered retrospectively. We studied prevalence and relevance of common
      allergens, performed dynamic patch test analysis and assessed occurrence of
      polysensitization. RESULTS: In 48 patients with difficult-to-treat AD, 75% (n =
      36/48) had a concomitant contact allergy, and 39% (n = 14/36) of these patients
      were polysensitized. ACD and polysensitization prevalences were equal amongst
      children and adults. The most frequent and relevant reactions were seen against
      wool alcohols, surfactants cocamidopropyl betaine and dimethylaminopropylamine,
      bichromate and fragrance mix I. Dynamic pattern analysis showed these reactions
      to be mostly allergic and not irritative of nature. CONCLUSION: Difficult-to
      treat AD patients frequently suffer from concomitant (multiple) contact
      allergies, and this may be a reason why the AD turns into a difficult-to-treat
      disease. Awareness of this phenomenon is necessary, as pragmatic implementation
      of allergen avoidance strategies may be helpful in getting disease control in
      this population.

PMID- 29578628
TI  - Assessment of two screening tools to identify psoriatic arthritis in patients
      with psoriasis.
AB  - BACKGROUND: Many patients with psoriasis have undiagnosed psoriatic arthritis.
      Low specificity is found with many PsA screening tools. A new instrument, the
      CONTEST questionnaire, was developed utilizing the most discriminative items from
      existing instruments. OBJECTIVE: The aim of this study was to compare the CONTEST
      and PEST screening tools. METHODS: People attending secondary care clinics with
      psoriasis, but not PsA, completed the questionnaires, were assessed for function
      and quality of life, and had a physical examination. Patients thought to have PsA
      were compared to those without. The performance of CONTEST and PEST was compared
      using area under the receiver operating curve (AUC), and sensitivity and
      specificity at the previously published cut-offs. RESULTS: A total of 451
      dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3
      21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95%
      CI) of PEST were 0.60 (0.42-0.78)/0.76 (0.69-0.83) and for CONTEST 0.53 (0.34
      0.72)/0.71 (0.63-0.79). The confidence limits for the AUC overlapped (AUC for
      PEST 0.72 (0.61-0.84), for CONTEST 0.66 (0.54-0.77). CONCLUSIONS: PEST and
      CONTEST questionnaires performed equally well, with no superiority of the new
      CONTEST tool.

PMID- 29578629
TI  - Response to Mroczkowski.

PMID- 29578630
TI  - Outcomes of radiation therapy of indolent cutaneous B-cell lymphomas and
      literature review.
AB  - BACKGROUND: Primary cutaneous B-cell lymphomas represent approximately 25% of
      primary cutaneous lymphomas. Follicular centre cell lymphomas (PCFCL) and
      marginal zone lymphomas (PCMZL) are the two histological subtypes that present an
      indolent evolution. Radiotherapy is one of the recommended treatment options with
      few series reported. OBJECTIVE: This study aimed to evaluate radiotherapy
      outcomes in term of overall survival (OS) and disease-free survival (DFS) for
      patients suffering from a PCMZL or PCFCL, to search for predictive factors of
      recurrence, and to evaluate chronic and aesthetics adverse events and patient's
      satisfaction. METHODS: Patients treated with contact low energy radiotherapy for
      a PMZCL or PCFCL from April 2009 to June 2017 in Saint Louis hospital were
      retrospectively analysed. Total dose ranged from 18 to 30 Gy. Objective response
      (OR) rates, DFS and OS as patterns of recurrence according to radiation fields
      were analysed. Univariate analysis of DFS has been performed according to
      clinical and biological parameters. Acute toxicity, long-term adverse events and
      satisfaction were collected via individualized questionnaires. RESULTS: Forty-six
      patients were included. Median follow-up was 43.5 months. OR was achieved for
      100% of cases. Recurrence occurred in 39% of cases. Median DFS was 44 months.
      Three-year DFS and 5-year DFS were 56% and 51%, respectively. OS at 3 and 5 year
      was 100%. Only sex was significantly associated with DFS. Acute AEs occurred in
      48% of cases without grade 3 and 4. 55% reported some moderate aesthetic sequelae
      for long-term AEs. 97% were satisfied with treatment. CONCLUSION: This study
      confirms the good risk-benefit of radiotherapy for the treatment of primary
      cutaneous indolent B-cell lymphomas due to the high response rate and a long DFS.
      No significant factor for recurrence was identified, except female sex. Long-term
      aesthetic evaluation was good or excellent for most of the patients.

PMID- 29578631
TI  - Coordination in theory, coordination in practice: the case of the Clusters.
AB  - The atomised nature of the humanitarian system has led to frequent and repeated
      attempts to coordinate humanitarian activity. Since 2005, some of the best
      resourced, and arguably most successful, coordination mechanisms have been the
      humanitarian Clusters, groups of UN (United Nations) and non-UN actors that
      engage in sectoral coordination of humanitarian response (such as the provision
      of healthcare and water) at the global and country level. Nevertheless, it is not
      clear exactly what 'coordination' means in the context of a Cluster. Formal
      guidance suggests that they should be aiming to create a single, joint strategy
      to guide the activities of members. Actual experience of the Clusters, however,
      indicates that looser forms of coordination are more effective. This finding
      resonates with organisational theory, and with the experience of emergency
      management professionals beyond the international humanitarian sector. To
      capitalise fully on the success of the Clusters, policymakers may need to rethink
      their attitudes to, and expectations of, coordination.

PMID- 29578632
TI  - A case of hereditary fibrosing poikiloderma with tendon contractures, myopathy
      and pulmonary fibrosis (POIKTMP) with the emphasis on cutaneous histopathological
      findings.

PMID- 29578633
TI  - Probing the Mint2 Protein-Protein Interaction Network Relevant to the
      Pathophysiology of Alzheimer's Disease.
AB  - The intracellular adaptor protein Mint2 binds amyloid precursor protein (APP) and
      presenilin-1, which are both central constituents of the amyloidogenic pathway
      associated with Alzheimer's disease (AD). Additional interaction partners have
      also been suggested for Mint2; several of them are also pertinent to AD
      pathogenesis. However, no comparative mapping of the Mint2 protein-protein
      interaction network is available. Here we provide a systematic characterization
      of seven interaction partners and address their specificities towards the
      different binding domains of Mint2, which reveal domain-specific and -nonspecific
      interaction partners. Moreover, we show that the last two C-terminal amino acids
      of Mint2 are both important for the intramolecular interaction with the PDZ1
      domain and for the stability of Mint2.

PMID- 29578634
TI  - mTOR: A double-edged sword for diabetes.
AB  - Diabetes is both a metabolic and an immune disorder. One intriguing link between
      the two is the serine-threonine protein kinase mammalian target of rapamycin
      (mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR
      is a key regulator of fuel metabolism and function of both pancreatic islet beta
      cells and immune cells. Consequently, it seems that mTOR has both anti- and
      prodiabetic effects. On the one hand, activation of mTOR in beta cells can
      increase their growth and proliferation, opposing impairments of insulin
      secretion in diabetes. On the other, activation of mTOR signaling in specific
      immune cells alters their fuel metabolism, amplifying their contributions to beta
      cell dysfunction, contributing to the development of diabetes. In this review, we
      focus on roles of mTOR signaling in pancreatic beta cells and immune cells and
      their implications in the pathogenesis and treatment of diabetes.

PMID- 29578635
TI  - Impact of the mechanical hyperkeratotic lesions and its association with quality
      of life: An observational case-control study.
AB  - BACKGROUND: Mechanical hyperkeratotic lesions (MHL) are common condition amongst
      population of all ages. Such problems may be associated with pain, reduction in
      mobility, changes of gait and risk of falls and is believed to affect the quality
      of life (QoL), general health and optimal foot health. OBJECTIVE: The main aim of
      this study was to describe and compare both foot and general health-related QoL
      in two groups of participants: (i) with MHL and (ii) healthy controls. METHOD: A
      total sample of 150 patients, mean age 49.50 +/- 36.50 years, was recruited from
      an outpatient clinic. Demographic data, medical history and clinical
      characteristics of overall health were determined, and the obtained values were
      compared by the Foot Health Status Questionnaire (FHSQ). RESULTS: The FHSQ scores
      of the sample with MHL showed lower scores than control subjects in sections one
      and two for footwear, general and foot health, foot pain, foot function and
      physical activity (P < 0.01), but not for social capacity and vigour (P > 0.01).
      CONCLUSIONS: People with MHL showed a decrease in QoL, based on FHSQ scores,
      regardless of gender.

PMID- 29578636
TI  - Octacarbonyl Anion Complexes of Group Three Transition Metals [TM(CO)8 ]- (TM=Sc,
      Y, La) and the 18-Electron Rule.
AB  - We report the gas-phase synthesis of stable 20-electron carbonyl anion complexes
      of group 3 transition metals, TM(CO)8- (TM=Sc, Y, La), which are studied by mass
      selected infrared (IR) photodissociation spectroscopy. The experimentally
      observed species, which are the first octacarbonyl anionic complexes of a TM, are
      identified by comparison of the measured and calculated IR spectra. Quantum
      chemical calculations show that the molecules have a cubic (Oh ) equilibrium
      geometry and a singlet (1 A1g ) electronic ground state. The 20-electron systems
      TM(CO)8- are energetically stable toward loss of one CO ligand, yielding the 18
      electron complexes TM(CO)7- in the 1 A1 electronic ground state; these exhibit a
      capped octahedral structure with C3v symmetry. Analysis of the electronic
      structure of TM(CO)8- reveals that there is one occupied valence molecular
      orbital with a2u symmetry, which is formed only by ligand orbitals without a
      contribution from the metal atomic orbitals. The adducts of TM(CO)8- fulfill the
      18-electron rule when only those valence electrons that occupy metal-ligand
      bonding orbitals are considered.

PMID- 29578637
TI  - The role of Confucianism in South Korea's emergency management system.
AB  - Numerous Western researchers have examined the influence of Confucianism on
      development in Asia, but almost no South Korean researchers have studied the
      topic in regard to emergency management in their own country. This study begins
      by considering Confucianism as a social culture. Next, it goes on to evaluate its
      role in South Korea's emergency management system, contributing, ultimately, to
      efficiencies in emergency management. Drawing on a literature review and a case
      study, the paper assesses the double- and single-faced approaches, using four
      major Confucian components: destiny; family; ritual; and relation. The double
      faced approach includes the positive and negative aspects of emergency
      management, whereas the single-faced approach incorporates only its positive
      aspects. This paper provides, for the first time, a systematic analysis of the
      relationship between Confucianism and emergency management in South Korea. Its
      key finding is that the double-faced approach needs to be transformed into a
      single-faced approach through active facilitation of behavioural change.

PMID- 29578638
TI  - Evaluation of the analytical variability of dipstick protein pads in canine
      urine.
AB  - BACKGROUND: The dipstick is a first-line and inexpensive test that can exclude
      the presence of proteinuria in dogs. However, no information is available about
      the analytical variability of canine urine dipstick analysis. OBJECTIVES: The aim
      of this study was to assess the analytical variability in 2 dipsticks and the
      inter-operator variability in dipstick interpretation. METHODS: Canine urine
      supernatants (n = 174) were analyzed with 2 commercially available dipsticks. Two
      observers evaluated each result blinded to the other observer and to the results
      of the other dipstick. Intra- and inter-assay variability was assessed in 5
      samples (corresponding to the 5 different semi-quantitative results) tested 10
      consecutive times over 5 consecutive days. The agreement between observers and
      between dipsticks was evaluated with Cohen's k test. RESULTS: Intra-assay
      repeatability was good (<=3/10 errors), whereas inter-assay variability was
      higher (from 1/5 to 4/5 discordant results). The concordance between the
      operators (k = 0.68 and 0.79 for the 2 dipsticks) and that of the dipsticks (k =
      0.66 and 0.74 for the 2 operators) was good. However, 1 observer and 1 dipstick
      overestimated the results compared with the second observer or dipstick. In any
      case, discordant results accounted for a single unit of the semi-quantitative
      scale. CONCLUSIONS: As for any other method, analytic variability may affect the
      semi-quantitation of urinary proteins when using the dipstick method. Subjective
      interpretation of the pad and, to a lesser extent, intrinsic staining properties
      of the pads could affect the results. Further studies are warranted to evaluate
      the effect of this variability on clinical decisions.

PMID- 29578639
TI  - Hormone modulation of legume-rhizobial symbiosis.
AB  - Leguminous plants can establish symbiotic associations with diazotropic rhizobia
      to form nitrogen-fixating nodules, which are classified as determinate or
      indeterminate based on the persistence of nodule meristem. The formation of
      nitrogen-fixing nodules requires coordinating rhizobial infection and root nodule
      organogenesis. The formation of an infection thread and the extent of nodule
      formation are largely under plant control, but vary with environmental conditions
      and the physiological state of the host plants. Many achievements in these two
      areas have been made in recent decades. Phytohormone signaling pathways have
      gradually emerged as important regulators of root nodule symbiosis. Cytokinin,
      strigolactones (SLs) and local accumulation of auxin can promote nodule
      development. Ethylene, jasmonic acid (JA), abscisic acid (ABA) and gibberellic
      acid (GA) all negatively regulate infection thread formation and nodule
      development. However, salicylic acid (SA) and brassinosteroids (BRs) have
      different effects on the formation of these two nodule types. Some peptide
      hormones are also involved in nodulation. This review summarizes recent findings
      on the roles of these plant hormones in legume-rhizobial symbiosis, and we
      propose that DELLA proteins may function as a node to integrate plant hormones to
      regulate nodulation.

PMID- 29578640
TI  - Taste and Flavor Perceptions of Glucosinolates, Isothiocyanates, and Related
      Compounds.
AB  - Brassicaceae plants are renowned for their taste, aroma and trigeminal
      characteristics; predominantly bitter taste, sulfurous aroma, and pungency.
      Compounds responsible for these sensations include the glucosinolates (GSLs) and
      their hydrolysis products, particularly isothiocyanates (ITCs), but also sulfur
      containing volatile compounds. This article reviews the relative importance of
      taste and flavor perceptions resulting from such compounds; collating evidence
      from papers where findings are based on sensory analytical correlations, and
      those that have extracted specific compounds prior to sensory evaluation. Where
      specific GSLs impart bitterness and many ITCs impart pungency, this is clearly
      not true for all GSLs and ITCs. Designing crop improvement strategies for sensory
      traits based on total GSL content would be flawed, as it does not consider the
      relative differences in sensory characteristics of different GSLs and ITCs, nor
      the contribution from other GSL hydrolysis products. In addition, some
      Brassicaceae plants are consumed raw, whilst others are cooked; this affects not
      only the hydrolysis of GSLs, but also the generation and release of sulfides.
      Therefore, in breeding new plant varieties, it is prudent to consider the
      individual GSLs, the typical cooking conditions the plant is subjected to, enzyme
      stability, and resultant composition of both GSL hydrolysis products (including
      ITCs) and sulfides.

PMID- 29578641
TI  - Comparative susceptibility and immune responses of Asian and European honey bees
      to the American foulbrood pathogen, Paenibacillus larvae.
AB  - American foulbrood (AFB) disease is caused by Paenibacillus larvae. Currently,
      this pathogen is widespread in the European honey bee-Apis mellifera. However,
      little is known about infectivity and pathogenicity of P. larvae in the Asiatic
      cavity-nesting honey bees, Apis cerana. Moreover, comparative knowledge of P.
      larvae infectivity and pathogenicity between both honey bee species is scarce. In
      this study, we examined susceptibility, larval mortality, survival rate and
      expression of genes encoding antimicrobial peptides (AMPs) including defensin,
      apidaecin, abaecin, and hymenoptaecin in A. mellifera and A. cerana when infected
      with P. larvae. Our results showed similar effects of P. larvae on the survival
      rate and patterns of AMP gene expression in both honey bee species when bee
      larvae are infected with spores at the median lethal concentration (LC50 ) for A.
      mellifera. All AMPs of infected bee larvae showed significant upregulation
      compared with noninfected bee larvae in both honey bee species. However, larvae
      of A. cerana were more susceptible than A. mellifera when the same larval ages
      and spore concentration of P. larvae were used. It also appears that A. cerana
      showed higher levels of AMP expression than A. mellifera. This research provides
      the first evidence of survival rate, LC50 and immune response profiles of Asian
      honey bees, A. cerana, when infected by P. larvae in comparison with the European
      honey bee, A. mellifera.

PMID- 29578642
TI  - Immune configuration in hatchling snakes is affected by incubation moisture, and
      is linked to subsequent growth and survival in the field.
AB  - We incubated the eggs of field-caught keelback snakes (Tropidonophis mairii) on
      wet versus dry substrates to explore impacts of incubation conditions on white
      blood cell (WBC) concentrations and differential WBC counts of hatchlings. In a
      second, independent study young snakes were released into the field, allowing us
      to explore fitness correlates of WBC profiles. Dry incubation reduced embryonic
      survival and hatchling body size, thus decoupling egg size from hatchling size.
      Incubation conditions also altered WBC profiles. Lymphocyte and azurophil counts
      were related to hatchling body size but not to initial egg mass, whereas
      heterophil counts were related to both of these traits. The egg-size effect on
      heterophil counts may reflect a maternal effect on offspring immune
      configuration. The ratio of heterophils to lymphocytes (an index of stress) was
      higher in hatchlings from eggs incubated on dry substrates. Snakes with higher
      counts of lymphocytes at hatching were more likely to be recaptured as adults
      (H:L; an index of survival), whereas snakes with higher basophil counts exhibited
      more rapid growth. In summary, our experiments show that incubation moisture
      levels influence the immune configuration of hatchling snakes, and that variation
      among individuals in WBC counts at hatching is a significant predictor of an
      individual's fitness after it is released into the wild. The demonstrated link
      between incubation conditions and offspring fitness is likely to impose strong
      selection on maternal nest-site choice.

PMID- 29578643
TI  - Arabidopsis thaliana NOP10 is required for gametophyte formation.
AB  - The female gametophyte is crucial for sexual reproduction of higher plants, yet
      little is known about the molecular mechanisms underlying its development. Here,
      we report that Arabidopsis thaliana NOP10 (AtNOP10) is required for female
      gametophyte formation. AtNOP10 was expressed predominantly in the seedling and
      reproductive tissues, including anthers, pollen grains, and ovules. Mutations in
      AtNOP10 interrupted mitosis of the functional megaspore during early development
      and prevented polar nuclear fusion in the embryo sacs. AtNOP10 shares a high
      level of amino acid sequence similarity with Saccharomyces cerevisiae (yeast)
      NOP10 (ScNOP10), an important component of the H/ACA small nucleolar
      ribonucleoprotein particles (H/ACA snoRNPs) implicated in 18S rRNA synthesis and
      rRNA pseudouridylation. Heterologous expression of ScNOP10 complemented the
      mutant phenotype of Atnop10. Thus, AtNOP10 influences functional megaspore
      mitosis and polar nuclear fusion during gametophyte formation in Arabidopsis.

PMID- 29578644
TI  - Point of care diaphragm ultrasound in infants with bronchiolitis: A prospective
      study.
AB  - BACKGROUND: Bronchiolitis is the most common reason for hospitalization of
      children worldwide. Many scoring systems have been developed to quantify
      respiratory distress and predict outcome, but none of them have been validated.
      We hypothesized that the ultrasound evaluation of the diaphragm could quantify
      respiratory distress and therefore we correlated the ultrasound diaphragm
      parameters with outcome. METHODS: Prospective study of infants with bronchiolitis
      (1-12 months) evaluated in a pediatric emergency department. Ultrasonography
      examinations of the diaphragm was performed (diaphragm excursion [DE],
      inspiratory excursion [IS], inspiratory/expiratory relationship [I/E], and
      thickness at end-expiration [TEE] and at end-inspiration [TEI]; thickening
      fraction [TF]). RESULTS: We evaluated 61 infants, 50.8 % males. Mean TF was 47%
      (IQR 28.6-64.7), mean I/E 0.47 (+/- 0.15), mean DE 10.39 +/- 4 mm. There was a
      linear correlation between TF and oxygen saturation at first evaluation (P =
      0.006, r = 0.392). All children with lower values of TF required HFNC and one of
      them required CPAP. A higher IS was associated with the future need of
      respiratory support during admission (P = 0.007). IS correlated with the hours of
      oxygen delivery needed (P = 0.032, r = 0.422). TEI (t = 3.701, P = 0.002) was
      found to be main predictor of hours of oxygen delivery needed. CONCLUSION: This
      study described ultrasound diaphragmatic values of previously healthy infants
      with bronchiolitis. DE, IS, and TEI correlated with outcome. If confirmed in
      larger studies, bedside ultrasound semiology of the diaphragm can be a new
      objective tool for the evaluation and outcome prediction of infants with
      bronchiolitis.

PMID- 29578645
TI  - Harnessing the microbiome for human health.

PMID- 29578646
TI  - Pharmacokinetics, Safety, and Tolerability of Lamotrigine Chewable/Dispersible
      Tablet Following Repeat-Dose Administration in Healthy Chinese Volunteers.
AB  - In this open-label, single-center study, the pharmacokinetics, safety, and
      tolerability of lamotrigine chewable/dispersible tablets were assessed in healthy
      Chinese volunteers. Each volunteer (N = 16) received repeat doses of oral
      lamotrigine titrated from 25 mg to 50 mg to 100 mg over 42 days and was followed
      up for 10-17 days. Safety and tolerability were assessed throughout the study.
      Lamotrigine pharmacokinetic parameters were estimated using noncompartmental
      analysis. Overall, 15 (94%) volunteers completed the study. Lamotrigine serum
      concentrations peaked 2.5 hours postdose, with a mean terminal half-life of 36.8
      hours. The apparent lamotrigine oral clearance was 1577.88 mL/h. The accumulation
      ratios (day 14 vs day 1) were 2.53 and 2.58 for area under the curve and peak
      concentration, respectively. Lamotrigine 25 to 100 mg once daily exhibited dose
      proportional pharmacokinetics (based on area under the curve and peak
      concentration), following repeat dosing. Nine volunteers reported adverse events,
      2 experienced oropharyngeal pain, each receiving 25 mg and 50 mg. One volunteer
      withdrew due to an increase in liver enzymes. No deaths, serious adverse effects,
      or skin rashes were reported during the study. No new safety concerns were
      observed. Overall, the pharmacokinetic profiles after repeat doses of lamotrigine
      chewable/dispersible tablets once daily in a Chinese population were similar to
      those observed in Western populations.

PMID- 29578647
TI  - Bioequivalence of Two Formulations of Gliclazide in a Randomized Crossover Study
      in Healthy Caucasian Subjects Under Fasting Conditions.
AB  - This study aimed to investigate the bioequivalence of 2 formulations of
      gliclazide modified-release tablets 60 mg in 48 healthy Caucasian volunteers
      under fasting conditions. A test product, Gliclazide MR (Ranbaxy Laboratories
      Limited, now Sun Pharmaceutical Industries, India), was compared with a reference
      product, Diamicron MR (Servier, France). The study was performed under a single
      dose, 2-treatment, 2-period, 2-sequence crossover design in a fasted condition
      with a washout period of 21 days. Blood samples were collected for 96 hours after
      drug administration. Drug plasma concentrations were determined by a liquid
      chromatography-tandem mass spectrometry method. Analysis of pharmacokinetic
      characteristics was based on a noncompartmental model. The logarithmically
      transformed data of Cmax and AUC were analyzed for 90% confidence intervals using
      analysis of variance. There was no significant difference in pharmacokinetic
      characteristics between the products, and the 90% confidence intervals were
      within the acceptance range of 80.00%-125.00%. The investigated products were
      bioequivalent under fasted conditions.

PMID- 29578649
TI  - Assessing the impact of the Graduate Certificate in Anatomical Sciences
      Instruction: A post-degree survey.
AB  - There are few graduate programs available for pursuing a doctorate in anatomy
      where students gain specific training in gross anatomy dissection and the
      responsibilities of a medical educator. In light of this fact, the University of
      Kentucky created a Graduate Certificate in Anatomical Sciences Instruction in
      2006. This 12-credit hour curriculum includes detailed training in gross anatomy
      and/or neuroscience courses, practicum experiences, a seminar class in
      pedagogical literature, and a course in educational strategies for the anatomical
      sciences. The award of certificate completion affirms that the candidate has
      demonstrated faculty-supervised proficiency in anatomy dissection, instruction in
      anatomy topics, and teaching strategies for anatomy. Seventeen graduate students
      have earned the certificate since its inception; nine students accepted teaching
      positions in anatomy following their graduate training and currently nine
      certificate graduates have assistant (six) or associate (three) professor
      positions in academia. In 2016, an anonymous survey including Likert-style and
      open-ended questions was emailed to all certificate graduates. Graduates
      favorably responded (each question averaged 4.4 or greater out of 5) that the
      certificate increased their awareness of teaching-faculty responsibilities,
      adequately prepared them for teaching-related duties, and positively contributed
      toward their first employment. Graduates indicated that the lecturing and
      dissection experience, awareness of faculty responsibilities, and job preparation
      (e.g., teaching philosophy development) were the most helpful aspects of the
      certificate. These results indicate that the Graduate Certificate in Anatomical
      Sciences Instruction is viewed by its graduates and their employers as a valuable
      teaching credential that can be attained alongside a basic science degree. Anat
      Sci Educ 11: 516-524. (c) 2018 American Association of Anatomists.

PMID- 29578648
TI  - Identifying Small-Molecule Binding Sites for Epigenetic Proteins at Domain-Domain
      Interfaces.
AB  - Epigenetics is a rapidly growing field in drug discovery. Of particular interest
      is the role of post-translational modifications to histones and the proteins that
      read, write, and erase such modifications. The development of inhibitors for
      reader domains has focused on single domains. One of the major difficulties of
      designing inhibitors for reader domains is that, with the notable exception of
      bromodomains, they tend not to possess a well-enclosed binding site amenable to
      small-molecule inhibition. As many of the proteins in epigenetic regulation have
      multiple domains, there are opportunities for designing inhibitors that bind at a
      domain-domain interface which provide a more suitable interaction pocket.
      Examination of X-ray structures of multiple domains involved in recognising and
      modifying post-translational histone marks using the SiteMap algorithm identified
      potential binding sites at domain-domain interfaces. For the tandem plant
      homeodomain-bromodomain of SP100C, a potential inter-domain site identified
      computationally was validated experimentally by the discovery of ligands by X-ray
      crystallographic fragment screening.

PMID- 29578650
TI  - Quantification of alignment of vascular smooth muscle cells.
AB  - Vascular smooth muscle cells (VSMCs) are essential components that keep the tonus
      of the arterial network, which is the channel used to conduct the blood from the
      heart to the peripheral areas of the body. It is known that mechanical and
      architectural changes in VSMCs may lead to functional modifications in the
      cardiovascular system; therefore, the quantitative characterization of these
      changes can help to elucidate questions that remain unclear in pathological
      situations, such as hypertension, vasospasm, vascular hypertrophy, and
      atherosclerosis. In this work, we have developed a new framework of image
      processing using the Sobel operator, associated with statistical analysis, to
      determine the degree of local alignment of actin filaments, which we found to be
      directly related with the distensibility of the arterial wall. We have also
      compared these results with the rigidity of the cytoskeleton of VSMCs. The
      results suggest that the alignment degree increases from peripheral arteries,
      such as carotid and femoral, to central arteries, as well coronary and thoracic
      aorta, which can indicate that the level of local alignment of the actin fibers
      in VSMCs is related with the mechanical behavior of the arterial wall. (c) 2018
      International Society for Advancement of Cytometry.

PMID- 29578651
TI  - Pilot Scale-up of Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Production by
      Halomonas bluephagenesis via Cell Growth Adapted Optimization Process.
AB  - Poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB), is one of the most
      valuable biopolymers because of its flexible mechanical properties. In this
      study, the goal is to establish a scaled-up process of low cost P(3HB-co-4HB)
      from a 7.5-L fermentor to 1- and 5-m3 industrial bioreactors, respectively, using
      Halomonas bluephagenesis TD40 grown on glucose, gamma-butyrolactone, and waste
      corn steep liquor (CSL) as substrates, under open non-sterile and fed-batch or
      continuous conditions. The non-sterile process enables the energy reduction for
      less steam consumption. Moreover, waste gluconate is successfully utilized to
      replace glucose as a carbon source for cell growth and PHA accumulation in 7.5-L
      fermentor, which opens the possibility of 60% of raw material cost reduction for
      recycling the waste resources. A mathematical model and rational calculation is
      established to help guide the feeding strategy and scale-up, respectively,
      leading to 100 g L-1 cell dry weight (CDW) containing 60.4% P(3HB-co-mol 13.5%
      4HB) after 36 h of growth in the 5 m3 vessel. An even higher P(3HB-co-4HB)
      content of 74% is achieved by decreasing the use of waste CSL. A stable and
      continuous open process for efficient low-cost production of P(3HB-co-4HB) is
      successfully developed coupling fermentation with the downstream extraction
      processing.

PMID- 29578652
TI  - Non-Celiac Gluten Sensitivity: How Its Gut Immune Activation and Potential
      Dietary Management Differ from Celiac Disease.
AB  - Non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the
      ingestion of gluten-containing grains leading to intestinal and/or
      extraintestinal symptoms that resolve once the gluten-containing foodstuff is
      eliminated from the diet, and it is diagnosed when celiac disease (CD) and wheat
      allergy (WA) have been ruled out. The limited knowledge about the pathophysiology
      of NCGS and the lack of validated biomarkers are still major limitations for
      clinical studies, making it difficult to differentiate NCGS from other gluten
      related disorders (GRD). In the absence of clear-cut diagnostic criteria, NCGS is
      still mainly a diagnosis of exclusion. Several studies suggest that NCGS is an
      immune-mediated disease that likely activates an innate immune response.
      Moreover, it has recently been hypothesized that in addition to gluten, other
      components of wheat may be responsible for the symptoms observed in individuals
      without CD. This review aims at discussing available evidence related to the
      histological and immunological features in the gut mucosa of patients with NCGS
      and at outlining new dietary opportunities for these patients.

PMID- 29578653
TI  - Diagnostic accuracy and therapeutic relevance of thoracoscopic lung biopsies in
      children.
AB  - INTRODUCTION: Histopathological assessment of lung biopsies does play an
      important diagnostic role in children's interstitial lung disease (ChILD).
      Thoracoscopic lung biopsy has been shown to be safe and effective. The aim of
      this study was to evaluate the diagnostic accuracy of thoracoscopic lung biopsies
      in children with ChILD. Furthermore, therapeutic relevance of the procedure,
      operative details, and perioperative complications of our series were
      investigated. METHODS: We retrospectively reviewed all consecutive thoracoscopic
      lung biopsies taken from children with suspected ChILD in our institution over an
      11-year period. Feasibility and complications were evaluated as well as
      histopathological diagnoses according to the recent ChILD classification and
      relevance of the procedure for medical treatment. RESULTS: Fifty-nine patients
      (54.2% male, median age 7 years [8 d-18 y]) underwent 112 thoracoscopic lung
      biopsies. An endostapler (27%), endoloop ligature (63%), or cut and suture
      technique (10%) were used. A chest tube was placed in 54% of the cases.
      Complications occurred in 15% of cases and mainly consisted of pneumothoraces or
      bleedings. Adequate tissue was obtained in all but one case and the biopsy led to
      a specific diagnosis according to the ChILD classification in 98%. Medical
      treatment of the underlying disease was changed due to the results of the biopsy
      in 86%. CONCLUSIONS: The diagnostic accuracy of thoracoscopic lung biopsies in
      children with suspected ChILD is high. The histopathologic results lead to a
      disease-specific treatment in the majority of the cases. Thoracoscopic lung
      biopsy is a safe and effective procedure with a low complication rate.

PMID- 29578654
TI  - Typological thinking: Then and now.
AB  - A popular narrative about the history of modern biology has it that Ernst Mayr
      introduced the distinction between "typological thinking" and "population
      thinking" to mark a contrast between a metaphysically problematic and a promising
      foundation for (evolutionary) biology, respectively. This narrative sometimes
      continues with the observation that, since the late-20th century, typological
      concepts have been making a comeback in biology, primarily in the context of
      evolutionary developmental biology. It is hard to square this narrative with the
      historical and philosophical literature on the typology/population distinction
      from the last decade or so. The conclusion that emerges from this literature is
      that the very distinction between typological thinking and population thinking is
      a piece of mere rhetoric that was concocted and rehearsed for purely strategic,
      programmatic reasons. If this is right, it becomes hard to make sense of recent
      criticisms (and sometimes: espousals) of the purportedly typological
      underpinnings of certain contemporary research programs. In this article, I offer
      a way out of this apparent conflict. I show that we can make historical and
      philosophical sense of the continued accusations of typological thinking by
      looking beyond Mayr, to his contemporary and colleague George Gaylord Simpson. I
      show that before Mayr discussed the typology/population distinction as an issue
      in scientific metaphysics, Simpson introduced it to mark several contrasts in
      methodology and scientific practice. I argue that Simpson's insightful discussion
      offers useful resources for classifying and assessing contemporary attributions
      of typological thinking.

PMID- 29578655
TI  - Robotic lateral pelvic lymph node dissection in rectal cancer - a video vignette.

PMID- 29578657
TI  - Reproducibility, stability, and biological variability of thrombin generation
      using calibrated automated thrombography in healthy dogs.
AB  - BACKGROUND: Thrombin plays a central role in hemostasis and thrombosis.
      Calibrated automated thrombography (CAT), a thrombin generation assay, may be a
      useful test for hemostatic disorders in dogs. OBJECTIVES: To describe CAT results
      in a group of healthy dogs, and assess preanalytical variables and biological
      variability. ANIMALS: Forty healthy dogs were enrolled. METHODS: Lag time (Lag),
      time to peak (ttpeak), peak thrombin generation (peak), and endogenous thrombin
      potential (ETP) were measured. Direct jugular venipuncture and winged-needle
      catheter-assisted saphenous venipuncture were used to collect samples from each
      dog, and results were compared between methods. Sample stability at -80 degrees C
      was assessed over 12 months in a subset of samples. Biological variability of CAT
      was assessed via nested ANOVA using samples obtained weekly from a subset of 9
      dogs for 4 consecutive weeks. RESULTS: Samples for CAT were stable at -80 degrees
      C over 12 months of storage. Samples collected via winged-needle catheter
      venipuncture showed poor repeatability compared to direct venipuncture samples;
      there was also poor agreement between the 2 sampling methods. Intra-individual
      variability of CAT parameters was below 25%; inter-individual variability ranged
      from 36.9% to 78.5%. CONCLUSIONS: Measurement of thrombin generation using CAT
      appears to be repeatable in healthy dogs, and samples are stable for at least 12
      months when stored at -80 degrees C. Direct venipuncture sampling is recommended
      for CAT. Low indices of individuality suggest that subject-based reference
      intervals are more suitable when interpreting CAT results.

PMID- 29578658
TI  - Ethical issues associated with HIV phylogenetics in HIV transmission dynamics
      research: A review of the literature using the Emanuel Framework.
AB  - The reduced costs of DNA sequencing and the use of such data for HIV-1 clinical
      management and phylogenetic analysis have led to a massive increase of HIV-1
      sequences in the last few years. Phylogenetic analysis has shed light on the
      origin, spread and characteristics of HIV-1 epidemics and outbreaks. Phylogenetic
      analysis is now also being used to advance our knowledge of the drivers of HIV-1
      transmission in order to design effective interventions. However, HIV
      phylogenetic analysis presents unique ethical challenges, which have not been
      fully explored. This review presents an analysis of what appear to be key ethical
      issues in HIV phylogenetics in the hope of stimulating further conceptual and
      empirical work in this rapidly emerging area. We structure the review using the
      Emanuel Framework, a systematic, holistic framework, which has been adapted for
      use in developing countries, which bear the brunt of the HIV-1 pandemic.

PMID- 29578673
TI  - Ligand-Based Phase Control in Porous Molecular Assemblies.
AB  - Functionalization of isophthalic acid ligands with linear alkoxide groups from
      ethoxy through pentoxy is shown to have a pronounced effect on both the synthesis
      of porous paddlewheel-based molecular assemblies and their resulting surface
      areas and gas adsorption properties. Shorter chain length is compatible with
      either tetragonal or hexagonal two-dimensional materials, with the hexagonal
      phase favored with longer chain length. Precise tuning of reaction conditions
      affords discrete molecular species that are soluble in a variety of organic
      solvents. The isolated porous molecules display BET surface areas ranging from
      125 m2/g to 545 m2/g. The pentoxide-based molecular assembly shows considerable
      promise for the separation of hydrocarbons with average isosteric heats of
      adsorption of -48 and -31 kJ/mol for ethylene and ethane, respectively.

PMID- 29578659
TI  - Drilling and Production Activity Related to Unconventional Gas Development and
      Severity of Preterm Birth.
AB  - BACKGROUND: Studies of unconventional gas development (UGD) and preterm birth
      (PTB) have not presented risk estimates by well development phase or trimester.
      OBJECTIVE: We examined phase and trimester-specific associations between UGD
      activity and PTB. METHODS: We conducted a case-control study of women with
      singleton births in the Barnett Shale area, Texas, from 30 November 2010 to 29
      November 2012. We individually age- and race/ethnicity-matched five controls to
      each PTB case (n=13,328) and truncated controls' time at risk according to the
      matched case's gestational age. We created phase-specific UGD-activity metrics:
      a) inverse squared distance-weighted (IDW) count of wells in the drilling phase
      <=0.5 mi (804.7 meters) of the residence and b) IDW sum of natural gas produced
      <=0.5 mi of the residence. We also constructed trimester- and gestation-specific
      metrics. Metrics were categorized as follows: zero wells (reference), first,
      second, third tertiles of UGD activity. Analyses were repeated by PTB severity:
      extreme, very, and moderate (<28, 28 to<32, and 32 to<37 completed weeks). Data
      were analyzed using conditional logistic regression. RESULTS: We found increased
      odds of PTB in the third tertile of the UGD drilling {odds ratio (OR)=1.20 [95%
      confidence interval (CI): 1.06, 1.37]} and UGD-production [OR=1.15 (1.05, 1.26)]
      metrics. Among women in the third tertile of UGD-production, associations were
      strongest in trimesters one [OR=1.18 (1.02, 1.37)] and two [OR=1.14 (0.99, 1.31).
      The greatest risk was observed for extremely PTB [third tertile ORs: UGD
      drilling, 2.00 (1.23, 3.24); UGD production, 1.53 (1.03-2.27)]. CONCLUSIONS: We
      found evidence of differences in phase- and trimester-specific associations of
      UGD and PTB and indication of particular risk associated with extremely preterm
      birth. Future studies should focus on quantifying specific chemical and
      nonchemical stressors associated with UGD. https://doi.org/10.1289/EHP2622.

PMID- 29578674
TI  - Proteomic Characterization of the Neural Ectoderm Fated Cell Clones in the
      Xenopus laevis Embryo by High-Resolution Mass Spectrometry.
AB  - The molecular program by which embryonic ectoderm is induced to form neural
      tissue is essential to understanding normal and impaired development of the
      central nervous system. Xenopus has been a powerful vertebrate model in which to
      elucidate this process. However, abundant vitellogenin (yolk) proteins in cells
      of the early Xenopus embryo interfere with protein detection by high-resolution
      mass spectrometry (HRMS), the technology of choice for identifying these gene
      products. Here, we systematically evaluated strategies of bottom-up proteomics to
      enhance proteomic detection from the neural ectoderm (NE) of X. laevis using
      nanoflow high-performance liquid chromatography (nanoLC) HRMS. From whole
      embryos, high-pH fractionation prior to nanoLC-HRMS yielded 1319 protein groups
      vs 762 proteins without fractionation (control). Compared to 702 proteins from
      dorsal halves of embryos (control), 1881 proteins were identified after yolk
      platelets were depleted via sucrose-gradient centrifugation. We combined these
      approaches to characterize protein expression in the NE of the early embryo. To
      guide microdissection of the NE tissues from the gastrula (stage 10), their
      precursor (midline dorsal-animal, or D111) cells were fate-mapped from the 32
      cell embryo using a fluorescent lineage tracer. HRMS of the cell clones
      identified 2363 proteins, including 147 phosphoproteins (without phosphoprotein
      enrichment), transcription factors, and members from pathways of cellular
      signaling. In reference to transcriptomic maps of the developing X. laevis, 76
      proteins involved in signaling pathways were gene matched to transcripts with
      known enrichment in the neural plate. Besides a protocol, this work provides
      qualitative proteomic data on the early developing NE.

PMID- 29578675
TI  - Polymer-Assisted Single Crystal Engineering of Organic Semiconductors To Alter
      Electron Transport.
AB  - A new crystal phase of a naphthalenediimide derivative (alpha-DPNDI) has been
      prepared via a facial polymer-assisted method. The stacking pattern of DPNDI can
      be tailored from the known one-dimensional (1D) ribbon (beta phase) to a novel
      two-dimensional (2D) plate (alpha phase) through the assistance from polymers. We
      believe that the presence of polymers during crystal growth is likely to weaken
      the direct pi-pi interactions and favor side-to-side C-H-pi contacts.
      Furthermore, beta phase architecture shows electron mobility higher than that of
      the alpha phase in the single-crystal-based OFET. Theoretical calculations not
      only confirm that beta-DPNDI has an electron transport performance better than
      that of the alpha phase but also indicate that the alpha phase crystal displays
      2D transport while the beta phase possesses 1D transport. Our results clearly
      suggest that polymer-assisted crystal engineering should be a promising approach
      to alter the electronic properties of organic semiconductors.

PMID- 29578676
TI  - Exploratory Study of Zn xPbO y Photoelectrodes for Unassisted Overall Solar Water
      Splitting.
AB  - A complete photoelectrochemical (PEC) water splitting system requires a
      photocathode and a photoanode to host water oxidation and reduction reactions,
      respectively. It is thus important to search for efficient photoelectrodes
      capable of full water splitting. Herein, we report on an exploratory study of a
      new photoelectrode family of Zn xPbO y-ZnPbO3 and Zn2PbO4-similarly synthesized
      by a simple and economical method and shown to be a promising photocathode (p
      type semiconductor) and photoanode (n-type semiconductor), respectively. From PEC
      measurements, the bare ZnPbO3 photocathode achieved a photocurrent density of 
      0.94 mA/cm2 at 0 V versus reversible hydrogen electrode (RHE), whereas the
      pristine Zn2PbO4 photoanode delivered a photocurrent density of 0.51 mA/cm2 at
      1.23 V versus RHE. By depositing suitable cocatalysts onto the photoelectrodes
      established above, we also demonstrated unassisted overall PEC water splitting, a
      rare case, if any, wherein a single material system is compositionally engineered
      for either of the photoelectrodes.

PMID- 29578677
TI  - Deterministic Design of Chemistry and Mesostructure in Li-Ion Battery Electrodes.
AB  - All battery electrodes have complex internal three-dimensional architectures that
      have traditionally been formed through the random packing of the electrode
      components. What is now emerging is a new concept in battery electrode design,
      where the important electronic and ionic pathways, as well as the chemical
      interactions between the components of the electrode, are deterministically
      designed. Deterministic design enables far better properties than are possible
      through random packing, including dramatic improvements in both power and energy.
      Such a design approach is particularly attractive for emerging high-energy
      density materials, which require available free volume as they swell during
      cycling. In addition to controlled structure, another important facet of the
      design of such systems is the stable chemical linkages between the active
      material and the conductive network that survive the lithiation and delithiation
      processes. In this Perspective, we discuss and provide our views on
      deterministically designed battery electrodes.

PMID- 29578678
TI  - Band Edge Dynamics and Multiexciton Generation in Narrow Band Gap HgTe
      Nanocrystals.
AB  - Mercury chalcogenide nanocrystals and especially HgTe appear as an interesting
      platform for the design of low cost mid-infrared (mid-IR) detectors.
      Nevertheless, their electronic structure and transport properties remain poorly
      understood, and some critical aspects such as the carrier relaxation dynamics at
      the band edge have been pushed under the rug. Some of the previous reports on
      dynamics are setup-limited, and all of them have been obtained using photon
      energy far above the band edge. These observations raise two main questions: (i)
      what are the carrier dynamics at the band edge and (ii) should we expect some
      additional effect (multiexciton generation (MEG)) as such narrow band gap
      materials are excited far above the band edge? To answer these questions, we
      developed a high-bandwidth setup that allows us to understand and compare the
      carrier dynamics resonantly pumped at the band edge in the mid-IR and far above
      the band edge. We demonstrate that fast (>50 MHz) photoresponse can be obtained
      even in the mid-IR and that MEG is occurring in HgTe nanocrystal arrays with a
      threshold around 3 times the band edge energy. Furthermore, the photoresponse can
      be effectively tuned in magnitude and sign using a phototransistor configuration.

PMID- 29578679
TI  - One-Pot Fabrication of Antireflective/Antibacterial Dual-Function Ag NP
      Containing Mesoporous Silica Thin Films.
AB  - Thin films that integrate antireflective and antibacterial dual functions are not
      only scientifically interesting but also highly desired in many practical
      applications. Unfortunately, very few studies have been devoted to the
      preparation of thin films with both antireflective and antibacterial properties.
      In this study, mesoporous silica (MSiO2) thin films with uniformly dispersed Ag
      nanoparticles (Ag NPs) were prepared through a one-pot process, which
      simultaneously shows high transmittance, excellent antibacterial activity, and
      mechanical robustness. The optimal thin-film-coated glass substrate demonstrates
      a maximum transmittance of 98.8% and an average transmittance of 97.1%,
      respectively, in the spectral range of 400-800 nm. The growth and multiplication
      of typical bacteria, Escherichia coli ( E. coli), were effectively inhibited on
      the coated glass. Pencil hardness test, tape adhesion test, and sponge washing
      test showed favorable mechanical robustness with 5H pencil hardness, 5A grade
      adhesion, and functional durability of the coating, which promises great
      potential for applications in various touch screens, windows for hygiene
      environments, and optical apparatuses for medical uses such as endoscope, and so
      on.

PMID- 29578680
TI  - Metal Ion/Tannic Acid Assembly as a Versatile Photothermal Platform in
      Engineering Multimodal Nanotheranostics for Advanced Applications.
AB  - This study reports a family of photothermal materials, metal ion/tannic acid
      assemblies (MITAs). MITAs from FeIII, VIII, and RuIII afford excellent
      photothermal efficiency (eta ~ 40%). Sharply differing from the currently
      existing photothermal agents, MITAs are highlighted by merits including green
      synthesis, facile incorporation of diagnostic metal ions, and particularly
      topology-independent adhesion. Owing to the adhesion nature of MITAs, various
      kinds of MITA-based nanoengineerings are readily available via the self-adhesion
      of MITAs onto diverse templates, enabling MITAs well suited as a photothermal
      platform for versatile combination with other therapy approaches and imaging
      techniques. As a proof of concept, polymeric/inorganic nanoparticle/nanovesicle
      supported FeIII-tannic acid (FeIIITA) is fabricated. The photothermal effect is
      shown to be unaffected by the template origin and type and FeIIITA thickness on
      the templates. We validate the potency of nanovesicle-supported FeIIITA
      (PNV@FeIIITA) for tumor-specific photoactivated utilizations, including NIR
      photothermal therapy with complete tumor elimination, photothermal imaging (PTI),
      and photoacoustic imaging (PAI) in addition to T1-MRI imaging. PNV@FeIIITA can be
      simultaneously equipped with functionalities, including T2-MRI imaging by
      additionally doping MnII and NIR fluorescence imaging by encapsulating a
      hydrophilic NIR fluoroprobe. MITA demonstrates unparalleled superiority as a
      photothermal platform in engineering multimodal theranostics for advanced
      applications.

PMID- 29578681
TI  - Solid-Phase Synthesis of beta-Hydroxy Ketones Via DNA-Compatible Organocatalytic
      Aldol Reactions.
AB  - One-bead one-compound (OBOC) libraries constructed by solid-phase split-and-pool
      synthesis are a valuable source of protein ligands. Most OBOC libraries are
      composed of oligoamides, particularly peptides, peptoids, and peptoid-inspired
      molecules. Further diversification of the chemical space covered by OBOC
      libraries is desirable. Toward this end, we report here that the proline
      catalyzed asymmetric aldol reaction, developed by List and Barbas for solution
      phase synthesis, also works well for coupling immobilized aldehydes and soluble
      ketones. These reaction conditions do not compromise the amplification of DNA by
      the polymerase chain reaction. Thus, this chemistry should be useful for the
      construction of novel DNA-encoded OBOC libraries by solid-phase synthesis.

PMID- 29578682
TI  - Zeolite-like Metal-Organic Framework (MOF) Encaged Pt(II)-Porphyrin for Anion
      Selective Sensing.
AB  - The selectivity and sensitivity of sensors are of great interest to the materials
      chemistry community, and a lot of effort is now devoted to improving these
      characteristics. More specifically, the selective sensing of anions is one of the
      largest challenges impeding the sensing-research area due to their similar
      physical and chemical behaviors. In this work, platinum-metalated porphyrin
      (Pt(II)TMPyP) was successfully encapsulated in a rho-type zeolite-like metal
      organic framework (rho-ZMOF) and applied for anion-selective sensing. The sensing
      activity and selectivity of the MOF-encaged Pt(II)TMPyP for various anions in
      aqueous and methanolic media were compared to that of the free (nonencapsulated)
      Pt(II)TMPyP. While the photoinduced triplet-state electron transfer of
      Pt(II)TMPyP showed a very low detection limit for anions with no selectivity, the
      Pt(II)TMPyP encapsulated in the rho-ZMOF framework possessed a unique chemical
      structure to overcome such limitations. This new approach has the potential for
      use in other complex sensing applications, including biosensors, which require
      ion selectivity.

PMID- 29578683
TI  - Immunohistochemical Approach to Understanding the Organization of the Olfactory
      System in the Cuttlefish, Sepia officinalis.
AB  - Cephalopods are nontraditional but captivating models of invertebrate
      neurobiology, particularly in evolutionary comparisons. Cephalopod olfactory
      systems have striking similarities and fundamental differences with vertebrates,
      arthropods, and gastropods, raising questions about the ancestral origins of
      those systems. We describe here the organization and development of the olfactory
      system of the common cuttlefish, Sepia officinalis, using immunohistochemistry
      and in situ hybridization. FMRFamide and/or related peptides and histamine are
      putative neurotransmitters in olfactory sensory neurons. Other neurotransmitters,
      including serotonin and APGWamide within the olfactory and other brain lobes,
      suggest efferent control of olfactory input and/or roles in the processing of
      olfactory information. The distributions of neurotransmitters, along with
      staining patterns of phalloidin, anti-acetylated alpha-tubulin, and a
      synaptotagmin riboprobe, help to clarify the structure of the olfactory lobe. We
      discuss a key difference, the lack of identifiable olfactory glomeruli, in
      cuttlefish in comparison to other models, and suggest its implications for the
      evolution of olfaction.

PMID- 29578684
TI  - Robust Mesoporous CoMo/gamma-Al2O3 Catalysts from Cyclodextrin-Based
      Supramolecular Assemblies for Hydrothermal Processing of Microalgae: Effect of
      the Preparation Method.
AB  - Hydrothermal liquefaction (HTL) is a promising technology for the production of
      biocrude oil from microalgae. Although this catalyst-free technology is efficient
      under high-temperature and high-pressure conditions, the biocrude yield and
      quality can be further improved by using heterogeneous catalysts. The design of
      robust catalysts that preserve their performance under hydrothermal conditions
      will be therefore very important in the development of biorefinery technologies.
      In this work, we describe two different synthetic routes (i.e., impregnation and
      cyclodextrin-assisted one-pot colloidal approach), for the preparation in aqueous
      phase of six high surface area CoMo/gamma-Al2O3 catalysts. Catalytic tests
      performed on the HTL of Nannochloropsis gaditana microalga indicate that solids
      prepared by the one-pot colloidal approach show higher hydrothermal stability and
      enhanced biocrude yield with respect to the catalyst-free test. The positive
      effect of the substitution of the block copolymer Tetronic T90R4 for Pluronic
      F127 in the preparation procedure was evidenced by diffuse reflectance UV-visible
      spectroscopy, X-ray diffraction, N2-adsorption-desorption, and H2-temperature
      programmed reduction measurements and confirmed by the higher quality of the
      obtained biocrude, which exhibited lower oxygen content and higher-energy
      recovery equal to 62.5% of the initial biomass.

PMID- 29578685
TI  - Inkjet Printing Enabled Controllable Paper Superhydrophobization and Its
      Applications.
AB  - Papers' intrinsic interconnected porous structures and hydrophilic properties
      usually results in difficulty and complexity in partial functionalization and
      regulation processes because the capillary effect may lead to the fast diffusion
      of modifiers from one side to the other. Here, we report a simple and innovative
      inkjet printing approach that led to precise hydrophobic functionalization
      controllable in both planar and steric dimensions. Fabrication of Janus
      superwetting papers and superwettable patterned papers with high precision was
      achieved by computer-controlled inkjet printing. Elaborate controls of ink
      quantity enabled superhydrophobic functionalization on one side of the paper
      substrate, with the opposite side superhydrophilic. Static water contact angles
      up to 154 degrees  were obtained on the inkjet-printed side of the paper, thanks
      to an appropriate combination of surface chemistry with dual-scale surface
      roughness. Furthermore, paper-based microfluidics were fabricated and the
      resolution of which were estimated to be ca. 600 MUm. Meanwhile, a paper-based
      analytical device for colorimetric sensing of Ni(II) was designed and
      demonstrated based on superwettable patterned papers by inkjet printing. The
      inkjet printing approach reported here represents a key step forward in
      fabricating Janus materials and complicate patterns for practical applications.

PMID- 29578686
TI  - Silicones for Stretchable and Durable Soft Devices: Beyond Sylgard-184.
AB  - This paper identifies and characterizes silicone elastomers that are well-suited
      for fabricating highly stretchable and tear-resistant devices that require
      interfacial bonding by plasma or UV ozone treatment. The ability to bond two or
      more pieces of molded silicone is important for creating microfluidic channels,
      chambers for pneumatically driven soft robotics, and other soft and stretchable
      devices. Sylgard-184 is a popular silicone, particularly for microfluidic
      applications. However, its low elongation at break (~100% strain) and moderate
      tear strength (~3 N/mm) make it unsuitable for emerging, mechanically demanding
      applications of silicone. In contrast, commercial silicones, such as Dragon Skin,
      have excellent mechanical properties yet are difficult to plasma-bond, likely
      because of the presence of silicone oils that soften the network yet migrate to
      the surface and interfere with plasma bonding. We found that extracting silicone
      oligomers from these soft networks allows these materials to bond but only when
      the Shore hardness exceeds a value of 15 A. It is also possible to mix highly
      stretchable silicones (Dragon Skin and Ecoflex) with Sylgard-184 to create
      silicones with intermediate mechanical properties; interestingly, these blends
      also only bond when the hardness exceeds 15 A. Eight different Pt-cured silicones
      were also screened; again, only those with Shore hardness above 15 A plasma-bond.
      The most promising silicones from this study are Sylgard-186 and Elastosil-M4130
      and M4630, which exhibit a large deformation (>200% elongation at break), high
      tear strength (>12 N/mm), and strong plasma bonding. To illustrate the utility of
      these silicones, we created stretchable electrodes by injecting a liquid metal
      into microchannels created using such silicones, which may find use in soft
      robotics, electronic skin, and stretchable energy storage devices.

PMID- 29578687
TI  - Esterase-Catalyzed Siderophore Hydrolysis Activates an Enterobactin-Ciprofloxacin
      Conjugate and Confers Targeted Antibacterial Activity.
AB  - Enteric Gram-negative bacteria, including Escherichia coli, biosynthesize and
      deploy the triscatecholate siderophore enterobactin (Ent) in the vertebrate host
      to acquire iron, an essential nutrient. We report that Ent-Cipro, a synthetic
      siderophore-antibiotic conjugate based on the native Ent platform that harbors an
      alkyl linker at one of the catechols with a ciprofloxacin cargo attached, affords
      targeted antibacterial activity against E. coli strains that express the pathogen
      associated iroA gene cluster. Attachment of the siderophore to ciprofloxacin, a
      DNA gyrase inhibitor and broad-spectrum antibiotic that is used to treat
      infections caused by E. coli, generates an inactive prodrug and guides the
      antibiotic into the cytoplasm of bacteria that express the Ent uptake machinery
      (FepABCDG). Intracellular hydrolysis of the siderophore restores the activity of
      the antibiotic. Remarkably, Fes, the cytoplasmic Ent hydrolase expressed by all
      E. coli, does not contribute to Ent-Cipro activation. Instead, this processing
      step requires IroD, a cytoplasmic hydrolase that is expressed only by E. coli
      that harbor the iroA gene cluster and are predominantly pathogenic. In the
      uropathogenic E. coli UTI89 and CFT073, Ent-Cipro provides antibacterial activity
      comparable to unmodified ciprofloxacin. This work highlights the potential of
      leveraging and targeting pathogen-associated microbial enzymes in narrow-spectrum
      antibacterial approaches. Moreover, because E. coli include harmless gut
      commensals as well as resident microbes that can contribute to disease, Ent-Cipro
      may provide a valuable chemical tool for strain-selective modulation of the
      microbiota.

PMID- 29578689
TI  - Ratiometric Fluorescent Biosensor for Visual Discrimination of Cancer Cells with
      Different Telomerase Expression Levels.
AB  - Telomerase is inactive in normal somatic cells but highly activated in tumor
      cells to maintain their indefinite proliferation and immortal phenotype. As a
      specific marker for the generation and progress of almost all tumors, the
      detection of telomerase activity by classical PCR techniques has served in the
      biological research of tumors. However, the detection of in situ telomerase
      activity in cell extracts to evaluate the malignancy, progress, and metastasis of
      tumors remains a daunting challenge. Here, a precisely designed FRET-based
      ratiometric fluorescent oligonucleotide probe has achieved high-fidelity
      detection of telomerase activity for accurate discrimination of different cancer
      cells toward advanced diagnosis of tumors. Our method is superior to other
      methods in its capabilities to quantify telomerase activity in cell extracts and
      visualize various tumor cell extracts with different telomerase expression levels
      by the naked eye for clinical diagnosis. In particular, the ratiometric
      fluorescent probe used in the assay could exclude other experimental factors
      influence, and further avoid false positive signal generation. The method
      reported here could provide a reliable, accurate, and convenient way in medical
      diagnostics and therapeutic response assessment.

PMID- 29578688
TI  - Unprecedented Role of Hybrid N-Glycans as Ligands for HIV-1 Broadly Neutralizing
      Antibodies.
AB  - The development of an HIV vaccine has been hampered by the extraordinary
      mutability and genetic diversity of the virus, particularly the substantial
      sequence diversity of gp120 and gp 41 envelope glycoproteins existing in more
      than 2000 HIV variants. The highly diverse glycans on HIV spikes are commonly
      considered as immunologically silent self-antigens; however, the discovery of
      highly potent broadly neutralizing antibodies (bNAbs) from HIV patients targeting
      the viral surface glycans has raised a major question about the origin of their
      antigens. Recent epitope mapping studies of the bNAb PG9 indicated a requirement
      of a properly spaced high mannose and a complex type glycan connected by a short
      peptide spacer. We have recently discovered that a 1:1 mixture of Man5 and sialyl
      biantennary glycan with well-defined distance and without the peptide spacer is
      well recognized by PG9 with high avidity and, thus, proposed that a hybrid glycan
      with oligomannose and complex-type arm could be the proper ligand of PG9. To
      verify this proposition, we first designed and chemo-enzymatically synthesized a
      series of unusual hybrid-type N-glycan structures, which may exist on HIV surface
      glycoproteins through the host-guided N-glycosylation pathway. The synthetic
      hybrid glycans were then used to prepare glycan arrays for the binding studies of
      PG9 and several other highly potent bNAbs, including PG16, PGT121, PGT128-3C,
      2G12, VRC13, VRC-PG05, VRC26.25, VRC26.09, PGDM1400, 35O22, and 10-1074. Our
      results demonstrated that PG9 and some other bNAbs bind with strong avidity
      (subnanomolar Kd) to certain hybrid structures, suggesting that these unusual
      glycans may serve as epitopes for the design of vaccines against HIV.

PMID- 29578690
TI  - Mitochondria-Targeting Peptoids.
AB  - Mitochondria-specific delivery methods offer a valuable tool for studying
      mitochondria-related diseases and provide breakthroughs in therapeutic
      development. Although several small-molecule and peptide-based transporters have
      been developed, peptoids, proteolysis-resistant peptidomimetics, are a promising
      alternative to current approaches. We designed a series of amphipathic peptoids
      and evaluated their cellular uptake and mitochondrial localization. Two peptoids
      with cyclohexyl residues demonstrated highly efficient cell penetration and
      mitochondrial localization without significant adverse effects on the cells and
      mitochondria. These mitochondria-targeting peptoids could facilitate the
      selective and robust targeted delivery of bioactive compounds, such as drugs,
      antioxidants, and photosensitizers, with minimal off-target effects.

PMID- 29578691
TI  - Removal of Arsenic from Strongly Acidic Wastewater Using Phosphorus Pentasulfide
      As Precipitant: UV-Light Promoted Sulfuration Reaction and Particle Aggregation.
AB  - Strongly acidic wastewater (H2SO4) with a high arsenic concentration is produced
      by many industries. The removal of arsenic by traditional sulfide (e.g., Na2S,
      FeS) from strongly acidic wastewater introduces cations (Na+ and Fe2+) to the
      solution, which may prevent the recycle of acid. In this study, a new sulfuration
      agent, phosphorus pentasulfide (P2S5) was employed, and its feasibility in
      arsenic removal from strongly acidic wastewater was investigated. In the dark,
      As(III) was efficiently removed, but the removal rate of As(V) was rather slow,
      which was the crucial defect for this method. We found that this defect can be
      efficiently overcome by UV irradiation through accelerating the formation and
      transformation of an intermediate species, monothioarsenate (H3AsO3S) in the
      As(V) removal process. In addition, the hydrolysis of P2S5 was enhanced under UV
      irradiation, which resulted in the increase of the arsenic removal efficiencies.
      Besides, the aggregation of the formed particles was also promoted. Different
      from FeS and Na2S, P2S5 introduces H3PO4 instead of cations to the solution,
      which can facilitate the recycle and reuse of arsenic and acid in strongly acidic
      wastewater.

PMID- 29578692
TI  - ATP-Linked Chimeric Nucleotide as a Specific Luminescence Reporter of
      Deoxyuridine Triphosphatase.
AB  - Nucleotide surveillance enzymes play important roles in human health, by
      monitoring damaged monomers in the nucleotide pool and deactivating them before
      they are incorporated into chromosomal DNA or disrupt nucleotide metabolism. In
      particular, deamination of cytosine, leading to uracil in DNA and in the
      nucleotide pool, can be deleterious, causing DNA damage. The enzyme deoxyuridine
      triphosphatase (dUTPase) is currently under study as a therapeutic and prognostic
      target for cancer. Measuring the activity of this enzyme is important both in
      basic research and in clinical applications involving this pathway, but current
      methods are nonselective, detecting pyrophosphate, which is produced by many
      enzymes. Here we describe the design and synthesis of a dUTPase enzyme-specific
      chimeric dinucleotide (DUAL) that replaces the pyrophosphate leaving group of the
      native substrate with ATP, enabling sensitive detection via luciferase
      luminescence signaling. The DUAL probe functions sensitively and selectively to
      quantify enzyme activities in vitro and in cell lysates. We further report the
      first measurements of dUTPase activities in eight different cell lines, which are
      found to vary by a factor of 7-fold. We expect that the new probe can be of
      considerable utility in research involving this clinically significant enzyme.

PMID- 29578693
TI  - Memristive Ion Channel-Doped Biomembranes as Synaptic Mimics.
AB  - Solid-state neuromorphic systems based on transistors or memristors have yet to
      achieve the interconnectivity, performance, and energy efficiency of the brain
      due to excessive noise, undesirable material properties, and nonbiological
      switching mechanisms. Here we demonstrate that an alamethicin-doped, synthetic
      biomembrane exhibits memristive behavior, emulates key synaptic functions
      including paired-pulse facilitation and depression, and enables learning and
      computing. Unlike state-of-the-art devices, our two-terminal, biomolecular
      memristor features similar structure (biomembrane), switching mechanism (ion
      channels), and ionic transport modality as biological synapses while operating at
      considerably lower power. The reversible and volatile voltage-driven insertion of
      alamethicin peptides into an insulating lipid bilayer creates conductive pathways
      that exhibit pinched current-voltage hysteresis at potentials above their
      insertion threshold. Moreover, the synapse-like dynamic properties of the
      biomolecular memristor allow for simplified learning circuit implementations. Low
      power memristive devices based on stimuli-responsive biomolecules represent a
      major advance toward implementation of full synaptic functionality in
      neuromorphic hardware.

PMID- 29578694
TI  - Depth Profiling and Cross-Sectional Laser Ablation Ionization Mass Spectrometry
      Studies of Through-Silicon-Vias.
AB  - Through-silicon-via (TSV) technology enables 3D integration of multiple 2D
      components in advanced microchip architectures. Key in the TSV fabrication is an
      additive-assisted Cu electroplating process in which the additives employed may
      get embedded in the TSV body. This incorporation negatively influences the
      reliability and durability of the Cu interconnects. Here, we present a novel
      approach toward the chemical analysis of TSVs which is based on femtosecond laser
      ablation ionization mass spectrometry (fs-LIMS). The conditions for LIMS depth
      profiling were identified by a systematic variation of the laser pulse energy and
      the number of laser shots applied. In this contribution, new aspects are
      addressed related to the analysis of highly heterogeneous specimens having
      dimensions in the range of the probing beam itself. Particularly challenging were
      the different chemical and physical properties of which the target specimens were
      composed. Depth profiling of the TSVs along their main axis (approach 1) revealed
      a gradient in the carbon (C) content. These differences in the C concentration
      inside the TSVs could be confirmed and quantified by LIMS analyses of cross
      sectionally sliced TSVs (approach 2). Our quantitative analysis revealed a C
      content that is ~1.5 times higher at the TSV top surface compared to its bottom.
      Complementary Scanning Auger Microscopy (SAM) data confirmed a preferential
      embedment of suppressor additives at the side walls of the TSV. These results
      demonstrate that the TSV filling concept significantly deviates from common
      Damascene electroplating processes and will therefore contribute to a more
      comprehensive, mechanistic understanding of the underlying mechanisms.

PMID- 29578695
TI  - A Review of Environmental Occurrence, Fate, Exposure, and Toxicity of
      Benzothiazoles.
AB  - Benzothiazole and its derivatives (BTs) are high production volume chemicals that
      have been used for several decades in a large number of industrial and consumer
      products, including vulcanization accelerators, corrosion inhibitors, fungicides,
      herbicides, algicides, and ultraviolet (UV) light stabilizers. Several
      benzothiazole derivatives are used commercially, and widespread use of these
      chemicals has led to ubiquitous occurrence in diverse environmental compartments.
      BTs have been reported to be dermal sensitizers, respiratory tract irritants,
      endocrine disruptors, carcinogens, and genotoxicants. This article reviews
      occurrence and fate of a select group of BTs in the environment, as well as human
      exposure and toxicity. BTs have frequently been found in various environmental
      matrices at concentrations ranging from sub-ng/L (surface water) to several tens
      of MUg/g (indoor dust). The use of BTs in a number of consumer products,
      especially in rubber products, has resulted in widespread human exposure. BTs
      undergo chemical, biological, and photolytic degradation in the environment,
      creating several transformation products. Of these, 2-thiocyanomethylthio
      benzothiazole (2-SCNMeS-BTH) has been shown to be the most toxic. Epidemiological
      studies have shown excess risks of cancers, including bladder cancer, lung
      cancer, and leukemia, among rubber factory workers, particularly those exposed to
      2-mercapto-benzothiazole (2-SH-BTH). Human exposure to BTs continues to be a
      concern.

PMID- 29578696
TI  - Microfluidic Chip with Integrated Electrophoretic Immunoassay for Investigating
      Cell-Cell Interactions.
AB  - Microfluidics have been used to create "body-on-chip" systems to mimic in vivo
      cellular interactions with a high level of control. Most such systems rely on
      optical observation of cells as a readout. In this work we integrated a cell-cell
      interaction chip with online microchip electrophoresis immunoassay to monitor the
      effects of the interaction on protein secretion dynamics. The system was used to
      investigate the effects of adipocytes on insulin secretion. Chips were loaded
      with 190 000 3T3-L1 adipocytes and a single islet of Langerhans in separate
      chambers. The chambers were perfused at 300-600 nL/min so that adipocyte
      secretions flowed over the islets for 3 h. Adipocytes produced 80 MUM of
      nonesterified fatty acids (NEFAs), a factor known to impact insulin secretion, at
      the islets. After perfusion, islets were challenged with a step change in glucose
      from 3 to 11 mM while monitoring insulin secretion at 8 s intervals by online
      immunoassay. Adipocyte treatment augmented insulin secretion by 6-fold compared
      to controls. The effect was far greater than comparable concentrations of NEFA
      applied to the islets demonstrating that adipocytes release multiple factors that
      can strongly potentiate insulin secretion. The experiments reveal that
      integration of chemical analysis with cell-cell interaction can provide valuable
      insights into cellular functions.

PMID- 29578697
TI  - Coencapsulation of (-)-Epigallocatechin-3-gallate and Quercetin in Particle
      Stabilized W/O/W Emulsion Gels: Controlled Release and Bioaccessibility.
AB  - Particle-stabilized W1/O/W2 emulsion gels were fabricated using a two-step
      procedure: ( i) a W1/O emulsion was formed containing saccharose (for osmotic
      stress balance) and gelatin (as a gelling agent) in the aqueous phase and
      polyglycerol polyricinoleate (a lipophilic surfactant) in the oil phase; ( ii)
      this W1/O emulsion was then homogenized with another water phase (W2) containing
      wheat gliadin nanoparticles (hydrophilic emulsifier). The gliadin nanoparticles
      in the external aqueous phase aggregated at pH 5.5, which led to the formation of
      particle-stabilized W1/O/W2 emulsion gels with good stability to phase
      separation. These emulsion gels were then used to coencapsulate a hydrophilic
      bioactive (epigallocatechin-3-gallate, EGCG) in the internal aqueous phase
      (encapsulation efficiency = 65.5%) and a hydrophobic bioactive (quercetin) in the
      oil phase (encapsulation efficiency = 97.2%). The emulsion gels improved EGCG
      chemical stability and quercetin solubility under simulated gastrointestinal
      conditions, which led to a 2- and 4-fold increase in their effective
      bioaccessibility, respectively.

PMID- 29578698
TI  - Enhanced Visible-Light-Driven Photocatalytic Bacterial Inactivation by Ultrathin
      Carbon-Coated Magnetic Cobalt Ferrite Nanoparticles.
AB  - Ultrathin hydrothermal carbonation carbon (HTCC)-coated cobalt ferrite (CoFe2O4)
      composites with HTCC coating thicknesses between 0.62 and 4.38 nm were fabricated
      as novel, efficient, and magnetically recyclable photocatalysts via a facile,
      green approach. The CoFe2O4/HTCC composites showed high magnetization and low
      coercivity, which favored magnetic separation for reuse. The results show that
      the close coating of HTCC on CoFe2O4 nanoparticles enhanced electron transfer and
      charge separation, leading to a significant improvement in photocatalytic
      efficiency. The composites exhibited superior photocatalytic inactivation toward
      Escherichia coli K-12 under visible-light irradiation, with the complete
      inactivation of 7 log10 cfu.mL-1 of bacterial cells within 60 min. The
      destruction of bacterial cell membranes was monitored by field-effect scanning
      electron microscopy analysis and fluorescence microscopic images. The bacterial
      inactivation mechanism was investigated in a scavenger study, and *O2, H2O2, and
      h+ were identified as the major reactive species for bacterial inactivation.
      Multiple cycle runs revealed that these composites had excellent stability and
      reusability. In addition, the composites showed good photocatalytic bacterial
      inactivation performance in authentic water matrices such as surface water
      samples and secondarily treated sewage effluents. The results of this work
      indicate that CoFe2O4/HTCC composites have great potential in large-scale
      photocatalytic disinfection operations.

PMID- 29578699
TI  - Stereochemical Course of Methyl Transfer by Cobalamin-Dependent Radical SAM
      Methyltransferase in Fosfomycin Biosynthesis.
AB  - The methyl groups of [ methyl-( S)]- and [ methyl-( R)]-[ methyl-D,T]-l
      methionine fed to Streptomyces fradiae were incorporated into fosfomycin, which
      was chemically degraded to chiral AcONa. The enzymatic test gave the ( S)
      configuration for the chiral AcONa derived from methionine with the ( S)
      [D,T]methyl group ( F = 31.7) and ( R) for the one derived from methionine with
      the ( R)-[D,T]methyl group ( F = 83.0). The radical SAM methyltransferase
      transfers the methyl group of MeCbl to HEP-CMP with inversion of configuration.

PMID- 29578700
TI  - Revisiting the Mechanism of Oxidative Unzipping of Multiwall Carbon Nanotubes to
      Graphene Nanoribbons.
AB  - Unzipping multiwall carbon nanotubes (MWCNTs) attracted great interest as a
      method for producing graphene nanoribbons (GNRs). However, depending on the
      production method, the GNRs have been proposed to form by different mechanisms.
      Here, we demonstrate that the oxidative unzipping of MWCNTs is intercalation
      driven, not oxidative chemical-bond cleavage as was formerly proposed. The
      unzipping mechanism involves three consecutive steps: intercalation-unzipping,
      oxidation, and exfoliation. The reaction can be terminated at any of these three
      steps. We demonstrate that even in highly oxidative media one can obtain
      nonoxidized GNR products. The understanding of the actual unzipping mechanism
      lets us produce GNRs with hybrid properties varying from nonoxidized through
      heavily oxidized materials. We answer several questions such as the reason for
      the innermost walls of the nanotubes remaining zipped. The intercalation-driven
      reaction mechanism provides a rationale for the difficulty in unzipping single
      wall and few-wall CNTs and aids in a reevaluation of the data from the oxidative
      unzipping process.

PMID- 29578701
TI  - Chemical Transformations in Confined Space of Coordination Architectures.
AB  - The scholastic significance of supramolecular chemistry continues to grow with
      the recent development of catalytic transformations in confined space of
      supramolecular architectures. It has come a long way from a natural cavity
      containing molecules to modern smart materials capable of manipulating reaction
      pathways. The rise of self-assembled coordination complexes provided a diverse
      array of host structures. Starting from purely organic compounds to metalloligand
      surrogates, supramolecular host cavities were tuned according to the requirement
      of the reactions. The understanding of their participation in a reaction led to
      better usage of those assemblies for specific reaction sequences. Commencing from
      cyclodextrin, a wide range of organic molecules was used for cage-catalyzed
      organic transformations. However, difficulties in synthesis and a tedious
      purification procedure led chemists to choose a different pathway of metal-ligand
      coordination-driven self-assembly. The latter stood out as a potential
      replacement of the organic cages, overcoming the previous drawbacks. In the glut
      of different transition-metal assemblies used for catalytic transformations, many
      of them showed chemo- and stereoselective products. However, the small cavity
      size in some of them led to premature failure of the reaction. In that context,
      "molecular barrels" showed good efficacy for the catalytic reaction sequence. The
      large cavity size and bigger orifice for intake of the substrate and easy release
      of the product made them a better choice for catalysis. Additionally these are
      mostly used in aqueous media, which reinforces the idea of green and
      environmentally nonhazardous chemistry. In this Viewpoint, we discuss the use of
      metal-ligand coordination-driven self-assembled molecular containers used for
      catalysis with special emphasis on molecular barrels. This paper built on
      existing literature provides a thorough development of the fertile ground of the
      coordination architecture for catalysis and its future direction of propagation.

PMID- 29578702
TI  - Faster Protocol for Endogenous Fatty Acid Esters of Hydroxy Fatty Acid (FAHFA)
      Measurements.
AB  - Fatty acid esters of hydroxy fatty acids (FAHFAs) are a recently discovered class
      of endogenous lipids with antidiabetic and anti-inflammatory activities. Interest
      in these lipids is due to their unique biological activites and the observation
      that insulin-resistant people have lower palmitic acid esters of hydroxystearic
      acid (PAHSA) levels, suggesting that a FAHFA deficiency may contribute to
      metabolic disease. Rigorous testing of this hypothesis will require the
      measurement of many clinical samples; however, current analytical workflows are
      too slow to enable samples to be analyzed quickly. Here we describe the
      development of a significantly faster workflow to measure FAHFAs that optimizes
      the fractionation and chromatography of these lipids. We can measure FAHFAs in 30
      min with this new protocol versus 90 min using the older protocol with comparable
      performance in regioisomer detection and quantitation. We also discovered through
      this optimization that oleic acid esters of hydroxystearic acids (OAHSAs),
      another family of FAHFAs, have a much lower background signal than PAHSAs, which
      makes them easier to measure. Our faster workflow was able to quantify changes in
      PAHSAs and OAHSAs in mouse tissues and human plasma, highlighting the potential
      of this protocol for basic and clinical applications.

PMID- 29578703
TI  - Electron Injection from Photoexcited Metal-Organic Framework Ligands to Ru2
      Secondary Building Units for Visible-Light-Driven Hydrogen Evolution.
AB  - We report the design of two new metal-organic frameworks (MOFs), Ru-TBP and Ru
      TBP-Zn, based on Ru2 secondary building units (SBUs) and porphyrin-derived
      tetracarboxylate ligands. The proximity of Ru2 SBUs to porphyrin ligands (~1.1
      nm) facilitates multielectron transfer from excited porphyrins to Ru2 SBUs to
      enable efficient visible-light-driven hydrogen evolution reaction (HER) in
      neutral water. Photophysical and electrochemical studies revealed oxidative
      quenching of excited porphyrin by Ru2 SBUs as the initial step of the HER process
      and the energetics of key intermediates in the catalytic cycle. Our work provides
      a new strategy to building multifunctional MOFs with synergistic ligands and SBUs
      for efficient photocatalysis.

PMID- 29578704
TI  - Complete Mechanism of Hemithioindigo Motor Rotation.
AB  - Hemithioindigo-based molecular motors are powered by nondamaging visible light
      and provide very fast directional rotations at ambient conditions. Their ground
      state energy profile has been probed in detail, but the crucial excited state
      processes are completely unknown so far. In addition, very fast processes in the
      ground state are also still elusive to date and thus knowledge of the whole
      operational mechanism remains to a large extent in the dark. In this work we
      elucidate the complete light-driven rotation mechanism by a combination of
      multiscale broadband transient absorption measurements covering a time scale from
      fs to ms in conjunction with a high level theoretical description of the excited
      state. In addition to a full description of the excited state dynamics in the
      various time regimes, we also provide the first experimental evidence for the
      elusive fourth intermediate ground state of the original HTI motor. The fate of
      this intermediate also is followed directly proving complete unidirectionality
      for both 180 degrees  rotation steps. At the same time, we uncover the hitherto
      unknown involvement of an unproductive triplet state pathway, which slightly
      diminishes the quantum yield of the E to Z photoisomerization. A rate model
      analysis shows that increasing the speed of motor rotation is most effectively
      done by increasing the photoisomerization quantum yields instead of barrier
      reduction for the thermal ratcheting steps. Our findings are of crucial
      importance for improved future designs of any light-driven molecular motor in
      general to yield better efficiencies and applicability.

PMID- 29578705
TI  - Understanding the Many-Body Basis Set Superposition Error: Beyond Boys and
      Bernardi.
AB  - : Fragment-based methods promise accurate energetics at a cost that scales
      linearly with the number of fragments. This promise is founded on the premise
      that the many-body expansion (or another similar energy decomposition) needs to
      only consider spatially local many-body interactions. Experience and chemical
      intuition suggest that typically at most four-body interactions are required for
      high accuracy. Bettens and co-workers [ J. Chem. Theory Comput. 2014 9, 3699
      3707] published a detailed study showing that for moderately sized water
      clusters, basis set superposition error (BSSE) undermines this premise.
      Ultimately, they were able to overcome BSSE by performing all computations in the
      supersystem basis set, but such a solution destroys the reduced computational
      scaling of fragment-based methods. Their findings led them to suggest that there
      is "trouble with the many-body expansion". Since then, a subsequent follow-up
      study from Bettens and co-workers [ J. Chem. THEORY: Comput. 2015, 11, 5132-5143]
      as well as a related study by Mayer and Bako [ J. Chem. Theory Comput. 2017, 13,
      1883-1886] have proposed new frameworks for understanding BSSE in the many-body
      expansion. Although the two frameworks ultimately propose the same working set of
      equations to the BSSE problem, their interpretations are quite different, even
      disagreeing on whether or not the solution is an approximation. In this work we
      propose a more general BSSE framework. We then show that, somewhat paradoxically,
      the two interpretations are compatible and amount to two different
      "normalization" conditions. Finally, we consider applications of these BSSE
      frameworks to small water clusters, where we focus on replicating high-accuracy
      coupled cluster benchmarks. Ultimately, we show for water clusters, using the
      present framework, that one can obtain results that are within +/-0.5 kcal mol-1
      of the coupled cluster complete basis set limit without considering anymore than
      a correlated three-body computation in a quadruple-zeta basis set and a four-body
      triple-zeta Hartree-Fock computation.

PMID- 29578706
TI  - Exploring an Artificial Metabolic Route in Fusarium sporotrichioides: Production
      and Characterization of 7-Hydroxy T-2 Toxin.
AB  - An artificial metabolic route to an unnatural trichothecene was designed by
      taking advantage of the broad substrate specificities of the T-2 toxin
      biosynthetic enzymes of Fusarium sporotrichioides. By feeding 7
      hydroxyisotrichodermin, a shunt pathway metabolite of F. graminearum, to a
      trichodiene synthase-deficient mutant of F. sporotrichioides, 7-hydroxy T-2 toxin
      (1) was obtained as the final metabolite. Such an approach may have future
      applications in the metabolic engineering of a variety of fungal secondary
      metabolites. The toxicity of 7-hydroxy T-2 toxin was 10 times lower than that of
      T-2 toxin in HL-60 cells.

PMID- 29578707
TI  - Carboxyl-Functionalized Nanoparticles Produced by Pulsed Plasma Polymerization of
      Acrylic Acid.
AB  - Carboxyl-enriched and size-selected polymer nanoparticles (NPs) may prove to be
      very useful in biomedical applications for linker-free binding of biomolecules
      and their transport to cells. In this study, we report about the synthesis of
      such NPs by low-pressure low-temperature pulsed plasma polymerization of acrylic
      acid. Gas aggregation cluster source was adapted to operate plasma with a
      constant pulse period of 50 MUs and with varying duty cycle. The NPs were
      produced with the size ranging from 31 +/- 5 to 93 +/- 14 nm and with retention
      of the carboxyl groups ranging from 4.0 to 12.0 atom %. Two regimes of the NP
      formation were identified. In the large duty cycle regime, the NP growth was
      interfered with by positive ion bombardment which resulted in the ion-driven
      detachment of the carboxyl species and in the formation of carboxyl-deficient
      NPs. In the small duty cycle regime, the NP growth was accompanied by the radical
      driven chain propagation with the attachment of intact monomer molecules.
      Improved efficacy of the monomer retention resulted in increased concentration of
      the carboxyl groups.

PMID- 29578708
TI  - ACC Deaminase from Lysobacter gummosus OH17 Can Promote Root Growth in Oryza
      sativa Nipponbare Plants.
AB  - Although Lysobacter species are a remarkable source of natural compounds with
      antibacterial and antifungal activities, the ability of these bacteria to produce
      plant growth promoters remains practically unknown. In this work, the ethylene
      precursor 1-aminocyclopropane-1-carboxylic acid (ACC) has been isolated from the
      secretions of Lysobacter gummosus OH17, indicating the presence of an ACC
      deaminase, which was shown to be encoded in the gene peg_1256. The recombinant
      enzyme could not only deaminate ACC to provide 2-oxobutanoic acid but also
      catalyzed the amination of the 2-oxobutanoic acid, demonstrating, for the first
      time, that ACC deaminases can produce ACC. After the treatment of rice Oryza
      sativa Nipponbare plants with OH17 ACC deaminase, the ethylene production levels
      were 44% higher in comparison with the control experiments, allowing significant
      improvements in root, 10%, and stem, 14%, growth.

PMID- 29578709
TI  - Conformational Preference Determined by C-H...pi Interaction of an O-H...O
      Hydrogen-Bonded Binary Complex of p-Fluorophenol with 2,5-Dihydrofuran: A Laser
      Induced Fluorescence Spectroscopy Study.
AB  - Conformational preferences of a binary hydrogen-bonded complex between p
      fluorophenol (pFP) and 2,5-dihydrofuran (DHF) have been studied by means of laser
      induced fluorescence (LIF) spectroscopy in a supersonic jet expansion.
      Calculation predicts two major conformers for this complex, one having a nearly
      linear geometry in which the two molecular moieties are bound only by an O-H...O
      H-bond, but in the other an additional C-H...pi type interaction between an ortho
      C-H group of pFP and ethylene group of DHF contributes to the binding
      stabilization and results in a folded geometry for the complex with respect to a
      global view, although the H-bond angle of the latter is relatively larger. This
      prediction is realized experimentally by identifying transitions corresponding to
      the two discrete conformers in a vibrationally resolved LIF excitation spectrum
      of the complex, and the red shifts of S1-S0 origin band of pFP moiety of the two
      conformers are 542 and 659 cm-1, respectively. The assignments are corroborated
      by means of dispersed fluorescence (DF) spectroscopy. In comparison, the LIF
      spectral bands for the pFP-tetrahydrofuran complex can be corresponded to only
      one conformer, whose S1-S0 origin transition shows a red shift (563 cm-1)
      somewhat similar to the linear conformer of pFP-DHF complex. Such similarities in
      spectral shifting behavior is consistent with the predictions of electronic
      structure calculations. The DF spectra also reveal that the energy threshold and
      pathways of vibrational dynamics in S1 of the two conformers show different
      behavior. Excitation to 6a1 level of pFP moiety of the folded conformer displays
      signatures of restricted intramolecular vibrational energy redistribution (IVR),
      whereas the linear form displays the emission feature for dissipative IVR.

PMID- 29578710
TI  - Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins.
AB  - FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display
      peptidyl-prolyl isomerase activities and act as coreceptors for
      immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs
      can enhance infectivity. However, developing druglike ligands for FKBPs or Mips
      has proven difficult, and many FKBPs and Mips still lack biologically useful
      ligands. To explore the scope and potential of C5-substituted [4.3.1]-aza
      bicyclic sulfonamides as a broadly applicable class of FKBP inhibitors, we
      developed a new synthesis method for the bicyclic core scaffold and used it to
      prepare an FKBP- and Mip-focused library. This allowed us to perform a systematic
      structure-activity-relationship analysis across key human FKBPs and microbial
      Mips, yielding highly improved inhibitors for all the FKBPs studied. A cocrystal
      structure confirmed the molecular-binding mode of the core structure and
      explained the affinity gained as a result of the preferred substituents. The best
      FKBP and Mip ligands showed promising antimalarial, antileginonellal, and
      antichlamydial properties in cellular models of infectivity, suggesting that
      substituted [4.3.1]-aza-bicyclic sulfonamides could be a novel class of anti
      infectives.

PMID- 29578711
TI  - Breakdown of the Simple Arrhenius Law in the Normal Liquid State.
AB  - It is common practice to discuss the temperature effect on molecular dynamics of
      glass formers above the melting temperature in terms of the Arrhenius law. Using
      dielectric spectroscopy measurements of dc conductivity and structural relaxation
      time on the example of the typical glass former propylene carbonate, we provide
      experimental evidence that this practice is not justified. Our conclusions are
      supported by employing thermodynamic density scaling and the occurrence of
      inflection points in isothermal dynamic data measured at elevated pressure.
      Additionally, we propose a more suitable approach to describe the dynamics both
      above and below the inflection point based on a modified MYEGA model.

PMID- 29578712
TI  - Selective Conversion of Methane by Rh1-Doped Aluminum Oxide Cluster Anions
      RhAl2O4-: A Comparison with the Reactivity of PtAl2O4.
AB  - Studying the elementary reactions of single-noble-metal-atom-doped species can
      give theoretical guidance for the design of related single-atom catalysis. Using
      a combination of mass spectrometry and density functional theory calculations,
      the reaction of RhAl2O4- with the most stable alkane molecule CH4 under thermal
      conditions has been studied. The methane tends to be converted into syngas (free
      H2 and adsorbed CO) with activation of four C-H bonds. In sharp contrast,
      formaldehyde was generated in the previously reported reaction of PtAl2O4- with
      CH4. Density functional theory calculations show that the difference in
      reactivity between RhAl2O4- and PtAl2O4- is found to be due to a higher energy
      barrier of the third C-H bond activation for the Pt analogue. This work provides
      the first comparative study on the reactivity of single noble-metal atoms (Rh,
      Pt) on the same cluster support (Al2O4-) and can be helpful for rational design
      of single-atom catalysts for selective methane conversion.

PMID- 29578713
TI  - The Effects of the Interplay between Motor and Brownian Forces on the Rheology of
      Active Gels.
AB  - Active gels perform key mechanical roles inside the cell, such as cell division,
      motion, and force sensing. The unique mechanical properties required to perform
      such functions arise from the interactions between molecular motors and
      semiflexible polymeric filaments. Molecular motors can convert the energy
      released in the hydrolysis of ATP into forces of up to piconewton magnitudes.
      Moreover, the polymeric filaments that form active gels are flexible enough to
      respond to Brownian forces but also stiff enough to support the large tensions
      induced by the motor-generated forces. Brownian forces are expected to have a
      significant effect especially at motor activities at which stable noncontractile
      in vitro active gels are prepared for rheological measurements. Here, a
      microscopic mean-field theory of active gels originally formulated in the limit
      of motor-dominated dynamics is extended to include Brownian forces. In the model
      presented here, Brownian forces are included accurately, at real room
      temperature, even in systems with high motor activity. It is shown that a subtle
      interplay, or competition, between motor-generated forces and Brownian forces has
      an important impact on the mass transport and rheological properties of active
      gels. The model predictions show that at low frequencies the dynamic modulus of
      active gels is determined mostly by motor protein dynamics. However, Brownian
      forces significantly increase the breadth of the relaxation spectrum and can
      affect the shape of the dynamic modulus over a wide frequency range even for
      ratios of motor to Brownian forces of more than a hundred. Since the ratio
      between motor and Brownian forces is sensitive to ATP concentration, the results
      presented here shed some light on how the transient mechanical response of active
      gels changes with varying ATP concentration.

PMID- 29578714
TI  - Easily Accessible Protein Nanostructures via Enzyme Mediated Addressing.
AB  - Site-specific formation of nanoscaled protein structures is a challenging task.
      Most known structuring methods are either complex and hardly upscalable or do not
      apply to biological matter at all. The presented combination of enzyme mediated
      autodeposition and nanosphere lithography provides an easy-to-apply approach for
      the buildup of protein nanostructures over a large scale. The key factor is the
      tethering of enzyme to the support in designated areas. Those areas are provided
      via prepatterning of enzymatically active antidots with variable diameters.
      Enzymatically triggered protein addressing occurs exclusively at the intended
      areas and continues until the entire active area is coated. After this, the
      reaction self-terminates. The major advantage of the presented method lies in its
      easy applicability and upscalability. Large-area structuring of entire support
      surfaces with features on the nanometer scale is performed efficiently and
      without the necessity of harsh conditions. These are valuable premises for large
      scale applications with potentials in biosensor technology, nanoelectronics, and
      life sciences.

PMID- 29578715
TI  - Enhanced Global Post-translational Modification Discovery with MetaMorpheus.
AB  - Correct identification of protein post-translational modifications (PTMs) is
      crucial to understanding many aspects of protein function in biological
      processes. G-PTM-D is a recently developed technique for global identification
      and localization of PTMs. Spectral file calibration prior to applying G-PTM-D,
      and algorithmic enhancements in the peptide database search significantly
      increase the accuracy, speed, and scope of PTM identification. We enhance G-PTM-D
      by using multinotch searches and demonstrate its effectiveness in identification
      of numerous types of PTMs including high-mass modifications such as
      glycosylations. The changes described in this work lead to a 20% increase in the
      number of identified modifications and an order of magnitude decrease in search
      time. The complete workflow is implemented in MetaMorpheus, a software tool that
      integrates the database search procedure, identification of coisolated peptides,
      spectral calibration, and the enhanced G-PTM-D workflow. Multinotch searches are
      also shown to be useful in contexts other than G-PTM-D by producing superior
      results when used instead of standard narrow-window and open database searches.

PMID- 29578716
TI  - Griseofamines A and B: Two Indole-Tetramic Acid Alkaloids with 6/5/6/5 and
      6/5/7/5 Ring Systems from Penicillium griseofulvum.
AB  - Two novel indole-tetramic acid alkaloids-griseofamine A (1) and griseofamine B
      (2)-and ( R)- N-(2-methylbutanoyl)-l-tryptophan (3), were isolated from the
      fungus Penicillium griseofulvum. Compounds 1 and 2 feature a 6/5/6/5 and 6/5/7/5
      tetracyclic ring systems formed by the fusion of an indole unit and a tetramic
      acid via a six or seven-membered N-heterocyclic ring, respectively. The plausible
      biosynthetic pathways of 1-3 are proposed. Compound 1 shows a weak anti
      inflammatory activity by inhibition of NO and TNF-alpha production.

PMID- 29578717
TI  - Superior Sensitivity of Copper-Based Plasmonic Biosensors.
AB  - Plasmonic biosensing has been demonstrated to be a powerful technique for
      quantitative determination of molecular analytes and kinetic analysis of
      biochemical reactions. However, interfaces of most plasmonic biosensors are made
      of noble metals, such as gold and silver, which are not compatible with
      industrial production technologies. This greatly limits biosensing applications
      beyond biochemical and pharmaceutical research. Here, we propose and investigate
      copper-based biosensor chips fully fabricated with a standard complementary metal
      oxide-semiconductor (CMOS) process. The protection of thin copper films from
      oxidation is achieved with SiO2 and Al2O3 dielectric films deposited onto the
      metal surface. In addition, the deposition of dielectric films with thicknesses
      of only several tens of nanometers significantly improves the biosensing
      sensitivity, owing to better localization of electromagnetic field above the
      biosensing surface. According to surface plasmon resonance (SPR) measurements,
      the copper biosensor chips coated with thin films of SiO2 (25 nm) and Al2O3 (15
      nm) show 55% and 75% higher sensitivity to refractive index changes,
      respectively, in comparison to pure gold sensor chips. To test biomolecule
      immobilization, the copper-dielectric biosensor chips are coated with graphene
      oxide linking layers and used for the selective analysis of oligonucleotide
      hybridization. The proposed plasmonic biosensors make SPR technology more
      affordable for various applications and provide the basis for compact biosensors
      integrated with modern electronic devices.

PMID- 29578718
TI  - Silver-Mediated Oxidative Decarboxylative Intramolecular Asymmetric Radical
      Cyclization (Csp3-Csp2) via Memory of Chirality: Access to Circumdatin Alkaloids.
AB  - A novel silver-mediated oxidative decarboxylative intramolecular asymmetric
      radical cyclization has been developed to form a Csp3-Csp2 bond via memory of
      chirality. The application of the process has been demonstrated for the synthesis
      of the circumdatin class of alkaloids in high enantiopurity with retention of the
      configuration. The developed protocol is mild and works with an inexpensive
      silver catalyst in the absence of ligand, base, or additives. The involvement of
      a monoradical in the reaction has been established by trapping the radical
      intermediate.

PMID- 29578719
TI  - Correction to "Total Synthesis of (-)-Geissoschizol through Ir-Catalyzed Allylic
      Amidation as the Key Step".

PMID- 29578720
TI  - Rhodium-Catalyzed C-O Bond Alkynylation of Aryl Carbamates with Propargyl
      Alcohols.
AB  - The rhodium-catalyzed alkynylation of aryl carbamates with propargyl alcohols is
      described. This methodology can provide aryl acetylenes from aryl carbamates via
      C-O bond activation. The use of propargyl alcohols as alkynylating agents allows
      the use of a variety of functional groups that are incompatible with
      organometallic nucleophiles. This reaction also serves to broaden the utility of
      a carbamate moiety as a convertible ortho directing group.

PMID- 29578721
TI  - Identification of an Endogenous Organosulfur Metabolite by Interpretation of Mass
      Spectrometric Data.
AB  - The chemical structure of x11564, a new endogenous organosulfur metabolite, was
      elucidated by de novo interpretation of mass spectrometric data. The structure
      was confirmed by comparison to a synthetic standard. Metabolite x11564 is
      structurally related to intermediates in the methionine salvage pathway.

PMID- 29578722
TI  - Anisotropic-Strain-Induced Band Gap Engineering in Nanowire-Based Quantum Dots.
AB  - Tuning light emission in bulk and quantum structures by strain constitutes a
      complementary method to engineer functional properties of semiconductors. Here,
      we demonstrate the tuning of light emission of GaAs nanowires and their quantum
      dots up to 115 meV by applying strain through an oxide envelope. We prove that
      the strain is highly anisotropic and clearly results in a component along the NW
      longitudinal axis, showing good agreement with the equations of uniaxial stress.
      We further demonstrate that the strain strongly depends on the oxide thickness,
      the oxide intrinsic strain, and the oxide microstructure. We also show that
      ensemble measurements are fully consistent with characterizations at the single
      NW level, further elucidating the general character of the findings. This work
      provides the basic elements for strain-induced band gap engineering and opens new
      avenues in applications where a band-edge shift is necessary.

PMID- 29578723
TI  - Ga-Doped Pt-Ni Octahedral Nanoparticles as a Highly Active and Durable
      Electrocatalyst for Oxygen Reduction Reaction.
AB  - Bimetallic PtNi nanoparticles have been considered as a promising electrocatalyst
      for oxygen reduction reaction (ORR) in polymer electrolyte membrane fuel cells
      (PEMFCs) owing to their high catalytic activity. However, under typical fuel cell
      operating conditions, Ni atoms easily dissolve into the electrolyte, resulting in
      degradation of the catalyst and the membrane-electrode assembly (MEA). Here, we
      report gallium-doped PtNi octahedral nanoparticles on a carbon support (Ga
      PtNi/C). The Ga-PtNi/C shows high ORR activity, marking an 11.7-fold improvement
      in the mass activity (1.24 A mgPt-1) and a 17.3-fold improvement in the specific
      activity (2.53 mA cm-2) compared to the commercial Pt/C (0.106 A mgPt-1 and 0.146
      mA cm-2). Density functional theory calculations demonstrate that addition of Ga
      to octahedral PtNi can cause an increase in the oxygen intermediate binding
      energy, leading to the enhanced catalytic activity toward ORR. In a voltage
      cycling test, the Ga-PtNi/C exhibits superior stability to PtNi/C and the
      commercial Pt/C, maintaining the initial Ni concentration and octahedral shape of
      the nanoparticles. Single cell using the Ga-PtNi/C exhibits higher initial
      performance and durability than those using the PtNi/C and the commercial Pt/C.
      The majority of the Ga-PtNi nanoparticles well maintain the octahedral shape
      without agglomeration after the single cell durability test (30,000 cycles). This
      work demonstrates that the octahedral Ga-PtNi/C can be utilized as a highly
      active and durable ORR catalyst in practical fuel cell applications.

PMID- 29578724
TI  - Transition-Metal-Free [3 + 2] Cycloaddition of Nitroolefins and
      Diazoacetonitrile: A Facile Access to Multisubstituted Cyanopyrazoles.
AB  - A transition-metal-free [3 + 2] cycloaddition reaction between nitroolefins and
      diazoacetonitrile (N2CHCN) is described. This protocol exhibits several merits
      including simple starting materials, mild reaction conditions, broad substrate
      scope, good yields, and regioselectivities. The one-pot three-component reaction
      of nitroolefins with diazoacetonitrile (N2CHCN) and alkyl halides is also
      developed, thus delivering a series of multisubstituted cyanopyrazoles in good to
      high yields.

PMID- 29578725
TI  - Matteson Homologation-Based Total Synthesis of Lagunamide A.
AB  - Matteson homologation was found to be an excellent tool for the synthesis of the
      polyketide fragment of lagunamide A. Starting from a chiral boronic ester, a
      central building block containing all stereogenic centers of the polyketide chain
      was synthesized via six iterative Matteson homologation steps.

PMID- 29578726
TI  - Cascade Radical 1,6-Addition/Cyclization of para-Quinone Methides: Leading to
      Spiro[4.5]deca-6,9-dien-8-ones.
AB  - A cascade three-component iodoazidation of para-quinone methides to construct
      spiro[4.5]deca-6,9-dien-8-ones under mild conditions has been developed. The
      chemoselective 1,6-addition of azide radical triggered a regioselective 5-exo-dig
      cyclization/radical coupling sequence, enabling C-N, C-C, and C-I bond formations
      in a one-pot procedure with high efficiency.

PMID- 29578727
TI  - Excitons in Core-Shell Nanowires with Polygonal Cross Sections.
AB  - The distinctive prismatic geometry of semiconductor core-shell nanowires leads to
      complex localization patterns of carriers. Here, we describe the formation of
      optically active in-gap excitonic states induced by the interplay between
      localization of carriers in the corners and their mutual Coulomb interaction. To
      compute the energy spectra and configurations of excitons created in the
      conductive shell, we use a multielectron numerical approach based on the exact
      solution of the multiparticle Hamiltonian for electrons in the valence and
      conduction bands, which includes the Coulomb interaction in a nonperturbative
      manner. We expose the formation of well-separated quasidegenerate levels, and
      focus on the implications of the electron localization in the corners or on the
      sides of triangular, square, and hexagonal cross sections. We obtain excitonic in
      gap states associated with symmetrically distributed electrons in the spin
      singlet configuration. They acquire large contributions due to Coulomb
      interaction, and thus are shifted to much higher energies than other states
      corresponding to the conduction electron and the vacancy localized in the same
      corner. We compare the results of the multielectron method with those of an
      electron-hole model, and we show that the latter does not reproduce the singlet
      excitonic states. We also obtain the exciton lifetime and explain selection rules
      which govern the recombination process.

PMID- 29578728
TI  - Diels-Alder Reactions with Ethylene and Superelectrophiles.
AB  - Diels-Alder reactions have been accomplished with ethylene as the dienophile
      through the use of inverse-electron demand Diels-Alder chemistry. As a key aspect
      of the chemistry, the dienes are part of tri- or dicationic superelectrophilic
      systems. Theoretical calculations reveal that the highly charged
      superelectrophiles possess exceptionally low lying LUMOs, and this facilitates
      the cycloaddition chemistry with ethylene. The chemistry has been used to prepare
      a series of tetrahydroquinoline products. This represents the first application
      of superelectrophilic activation in a cycloaddition reaction, and a new method of
      utilizing ethylene as a C2 building block.

PMID- 29578729
TI  - Mental health disorders and mental health problems, active component,U.S. Armed
      Forces, 2007-2016.
AB  - Mental health disorders have historically accounted for significant morbidity,
      healthcare utilization, disability, and attrition from military service. From
      2007 through 2016, a total of 853,060 active component service members were
      diagnosed with at least one mental health disorder and 115,378 were diagnosed
      with mental health problems related to family/support group problems,
      maltreatment, lifestyle problems, or substance abuse counseling. Annual incidence
      rates of at least one mental health disorder decreased by approximately 6.2%
      during the period. Most of the incident mental health disorder diagnoses were
      attributable to adjustment disorders, depressive disorders, and anxiety
      disorders. Similar to the findings of a previous MSMR report, rates of incident
      mental health disorders were generally higher among females and Army members, and
      declined with increasing age. The number of individuals affected by any mental
      health diagnosis during deployment to a U.S. Central Command area of
      responsibility decreased from 10,951 in 2008 to 3,239 in 2016. Ongoing efforts to
      assist and treat service members should continue to promote help-seeking behavior
      to improve psychological and emotional well-being of service members and reduce
      the burden of mental health disorders.

PMID- 29578730
TI  - Incidence rates of diagnoses of cardiovascular diseases and associated risk
      factors, active component, U.S. Armed Forces, 2007-2016.
AB  - During 2007-2016, 18.1% of all active component service members were diagnosed
      with at least one of the five risk factors for cardiovascular disease (CVD)
      studied in this analysis. In addition, 0.6% of service members were diagnosed
      with at least one of the four CVDs studied. The most frequently diagnosed risk
      factors were (in descending order of frequency) obesity, hyperlipidemia,
      essential hypertension, abnormal blood glucose level, and diabetes mellitus.
      Incidence rates of both risk factors and CVD were progressively higher with
      advancing age. Annual incidence rates during the 10-year period declined for the
      risk factors hyperlipidemia, hypertension, and diabetes, but rose for obesity and
      abnormal blood glucose level. Annual rates of the CVDs ischemic heart disease and
      cerebrovascular disease declined, but rates of hypertensive heart/kidney disease
      and atherosclerosis remained relatively stable. Noteworthy findings were the
      increase in incidence rates of obesity, the decline in incidence rates of
      ischemic heart disease, and the decline in rates of hypertension in non-Hispanic
      black service members. The identification of CVD risk factors, including others
      not studied in this analysis, offers the opportunity for preventive interventions
      that can reduce the rates of clinical CVD during, but especially after, military
      service.

PMID- 29578731
TI  - Herpes zoster, active component, U.S. Armed Forces, 2000-2016.
AB  - During 2000-2016, a total of 52,895 active component service members received
      incident diagnoses of herpes zoster (HZ), for an overall unadjusted incidence
      rate of 2.5 cases per 1,000 person-years (p-yrs). Compared to their respective
      counterparts, overall incidence rates of HZ were highest among females, those
      aged 50 years or older, and Air Force members. Overall rates generally increased
      with increasing age and were highest among non-Hispanic whites and Asian/Pacific
      Islanders and lowest among non-Hispanic blacks. Unadjusted annual incidence rates
      of HZ increased steadily from 2000 to a peak in 2014. From 2000 through 2016,
      annual rates of HZ increased in each service and increases in annual rates were
      seen in all race/ethnicity groups. Individuals who were identified as
      immunocompromised constituted 2.1% of the total incident HZ cases. During 2000
      2016, the cumulative numbers of incident cases of HZ were highest during June,
      July, and August. The increase in HZ incidence observed in this and many other
      studies is a public health concern that requires a better understanding of key
      risk factors. Additional research focused on these factors could make trends more
      interpretable, suggest new approaches for prevention and treatment of HZ, and
      allow for better targeting of existing strategies.

PMID- 29578732
TI  - Beer for "brohood": A laboratory simulation of masculinity confirmation through
      alcohol use behaviors in men.
AB  - Though alcohol use is a widespread behavior, men tend to drink more and
      experience more alcohol-related negative consequences than do women. Research
      suggests that individuals are motivated to maintain ingroup status by engaging in
      behaviors prototypical of the ingroup when group status has been threatened, and
      that men are particularly likely to do this when masculine ingroup status is
      threatened. The present study investigated masculine drinking behaviors through a
      social lens, examining the impact of masculinity threat on alcohol consumption in
      a simulated bar laboratory. Sixty-five male students ages 21-29 years (Mage =
      22.66; 74% White) consumed beer in a taste-test paradigm after being exposed to
      randomly assigned personality feedback relative to gender standards. This
      feedback suggested that they were either low in masculinity (threat condition, n
      = 22) or high in masculinity (control condition, n = 22). A third condition
      received the low-masculinity feedback and then were exposed to information to
      undermine masculine alcohol use norms (undermine condition, n = 21) to account
      for negative affect reduction motives for use. As hypothesized, individuals in
      the threat condition consumed significantly more alcohol than those in the
      control and undermine conditions, even though the threat and undermine conditions
      reported similar levels of negative affect following masculinity threat. These
      results suggest that consumption of alcohol by men in social contexts may be
      strongly motivated by the desire to confirm masculine status. This understanding
      may be used to enhance the effectiveness of alcohol use intervention protocols.
      (PsycINFO Database Record

PMID- 29578733
TI  - If you're high status and you know it: Teasing apart the within- and between
      person effects of peer- and self-reported status in the drinking group on alcohol
      related outcomes.
AB  - In this longitudinal study, we disentangled within- and between-persons effects
      in the relationship between university students' status in their drinking group
      and alcohol-related behavior. We further examined the role of self-perceived and
      peer-reported status, with the hypothesis that only when students' peers reported
      them as of a higher status, and they were aware of their high status (via self
      report), would they experience increased heavy episodic drinking (HED).
      University students (N = 118; Mage = 19.40, SD = 1.49; 60.2% women) were
      recruited in their natural drinking groups (N = 27). All group members completed
      surveys at 3 time points during the school year, each 2 months apart. We fitted a
      taxonomy of multilevel growth curve models predicting students' self-reported HED
      and the extent to which they encouraged other group members to consume alcohol
      (peer-reported). Between-persons results demonstrated that students who reported
      higher status compared to their group members experienced more HED on average and
      students who were peer-reported as of a higher status relative to their group
      members played a more salient role in encouraging others to drink. Notably, and
      consistent with hypotheses, a within-person interaction revealed that at time
      points when students were higher in peer-reported status relative to their
      average, and they were aware of their increase in status (via self-reports), they
      also engaged in more HED. Results emphasize the importance of considering within
      person effects and highlight the need for university alcohol-prevention
      programming to focus on students' status-related motives and concerns. (PsycINFO
      Database Record

PMID- 29578734
TI  - Investigating the incremental validity of cognitive variables in early
      mathematics screening.
AB  - The purpose of this study was to investigate the incremental validity of a set of
      domain general cognitive measures added to a traditional screening battery of
      early numeracy measures. The sample consisted of 458 kindergarten students of
      whom 285 were designated as severely at-risk for mathematics difficulty.
      Hierarchical multiple regression results indicated that Wechsler Abbreviated
      Scales of Intelligence (WASI) Matrix Reasoning and Vocabulary subtests, and Digit
      Span Forward and Backward measures explained a small, but unique portion of the
      variance in kindergarten students' mathematics performance on the Test of Early
      Mathematics Ability-Third Edition (TEMA-3) when controlling for Early Numeracy
      Curriculum Based Measurement (EN-CBM) screening measures (R2 change = .01).
      Furthermore, the incremental validity of the domain general cognitive measures
      was relatively stronger for the severely at-risk sample. We discuss results from
      the study in light of instructional decision-making and note the findings do not
      justify adding domain general cognitive assessments to mathematics screening
      batteries. (PsycINFO Database Record

PMID- 29578735
TI  - Establishing individual differences in perceptual capacity.
AB  - Limited capacity for visual perception results in various "inattentional
      blindness" phenomena across a wide variety of manipulations that load perception.
      Here, we propose that these phenomena are mediated by an underlying generalized
      capacity for visual perception, which also underlies subitizing: the ability to
      enumerate a limited number of items in parallel from a brief exposure. We tested
      this proposal by examining whether individual differences reveal common
      intraindividual variance between measures of visual perception as well as of
      subitizing capacity. Visual perception was measured in change blindness (Rensink,
      O'Regan, & Clark, 1997), load-induced blindness (Macdonald & Lavie, 2008), and
      multiple object tracking tasks. Subitizing capacity was measured as the number of
      items that could be reported in parallel in an enumeration task. Perceptual
      capacity as indexed by subitizing was consistently a unique predictor of
      performance in change blindness, load-induced blindness, and motion tracking
      beyond any general factors that apply to both subitizing and estimation of larger
      set sizes. Moreover, when measures of working memory were included, factor
      analysis indicated two orthogonal factors: perceptual and working memory.
      Overall, the results support the hypothesis of a generalized capacity for visual
      perception, and establish subitizing capacity as a predictor of individual
      susceptibility to inattentional blindness under load. (PsycINFO Database Record

PMID- 29578736
TI  - Part-list cuing can impair, improve, or not influence recall performance: The
      critical roles of encoding and access to study context at test.
AB  - The results of four experiments are reported, in which we examined how the
      effects of part-list cuing - the presentation of a random selection of studied
      items as retrieval cues at test - on recall of the remaining target items depend
      on encoding and access to study context at test. Encoding was varied by inducing
      high and low degrees of interitem associations; access to study context at test
      was varied by inducing high and low degrees of contextual overlap between study
      and test. Results showed that the effects of part-list cuing depend critically on
      encoding and study context access. Depending on the combination of the two, part
      list cuing impaired, improved, or did not influence recall of the target items. A
      multimechanisms account of part-list cuing is provided to explain how part-list
      cuing affects target recall in the different experimental conditions. (PsycINFO
      Database Record

PMID- 29578737
TI  - Liking goes with liking: An intuitive congruence between preference and
      prominence.
AB  - In a series of 8 experiments, we demonstrate the existence of a "labeling effect"
      wherein people intuitively relate preferred choices to prominently labeled cues
      (such as heads as opposed to tails in a coin toss) and vice versa. Importantly,
      the observed congruence is asymmetric-it does not manifest for nonprominent cues
      and nonpreferred choices. This is because the congruence is driven by a process
      of evaluative matching: prominent cues are liked, but nonprominent cues are
      neutral or at most slightly negative in contrast. When we test prominent, yet
      truly negatively labeled cues, we indeed find a matching with less liked
      products. We discuss the theoretical contributions to the study of preferences
      and decision making, as well as demonstrate the practical implications to
      researchers and practitioners by using this process to assess intuitive
      preferences and reduce the compromise effect. (PsycINFO Database Record

PMID- 29578738
TI  - An exploration of the role of subordinate affect in leader evaluations.
AB  - Leadership research has been encumbered by a proliferation of constructs and
      measures, despite little evidence that each is sufficiently conceptually and
      operationally distinct from the others. We draw from research on subordinates'
      implicit theories of leader behavior, behaviorally anchored rating scales, and
      decision making to argue that leader affect (i.e., the degree to which
      subordinates have positive and negative feelings about their supervisors)
      underlies the common variance shared by many leadership measures. To explore this
      possibility, we developed and validated measures of positive and negative leader
      affect (i.e., the Leader Affect Questionnaires; LAQs). We conducted 10 studies to
      develop the five-item positive and negative LAQs and to examine their convergent,
      discriminant, predictive, and criterion-related validity. We conclude that a) the
      LAQs provide highly reliable and valid tools for assessing subordinates'
      evaluations of their leaders; b) there is significant overlap between existing
      leadership measures, and a large proportion of this overlap is a function of the
      affect captured by the LAQs; c) when the LAQs are used as control variables, in
      most cases, they reduce the strength of relationships between leadership measures
      and other variables; d) the LAQs account for significant variance in outcomes
      beyond that explained by other leadership measures; and e) there is a
      considerable amount of unexplained variance between leadership measures that the
      LAQs do not capture. Research suggestions are provided and the implications of
      our results are discussed. (PsycINFO Database Record

PMID- 29578739
TI  - Proactivity despite discouraging supervisors: The powerful role of prosocial
      motivation.
AB  - Although considerable research demonstrates that employees are unlikely to be
      proactive when they view their supervisors as discouraging this type of behavior,
      we challenge the assumption that this is true for all employees. Drawing on
      motivated information processing theory, we argue that prosocial motivation can
      spark employees to be proactive even when supervisors are perceived as
      discouraging. Specifically, prosocial motivation may weaken the negative
      relationship between perceived discouraging supervisor behaviors and proactivity
      by driving employees to bring about change to impact coworkers or the
      organization. Because they are less focused on self-interest and more focused on
      benefitting others, prosocially motivated employees are able to maintain their
      reason-to (felt responsibility for change) and can-do (efficacy to be proactive)
      motivation even when supervisors do not welcome proactivity. We test our
      hypotheses across three studies, using multisource data from employees and
      supervisors in two organizations (Studies 1a and 1b), and lagged data from
      employees working in a range of industries (Study 2). By identifying the
      mechanisms driving prosocially motivated employees to be proactive despite having
      supervisors who are perceived to be discouraging, we offer novel theoretical and
      practical insights regarding the effects of context on proactivity at work.
      (PsycINFO Database Record

PMID- 29578740
TI  - Confirmatory factor analysis of the Coping Strategies Questionnaire-Revised for
      veterans with pain.
AB  - As the need for appropriate assessment and treatment of veterans with chronic
      pain continues to grow, it is important to ensure that the instruments we use to
      complete these assessments, such as the Coping Strategies Questionnaire-Revised
      (CSQ-R), are validated on this population. The purpose of the present study was
      to confirm the factor structure of the CSQ-R in veterans. Secondary analyses
      examined associations between various pain coping strategies and measures of mood
      and health functioning. Participants consisted of 281 veterans who were referred
      to and evaluated by a Psychology Pain Management Program in a northeastern
      Department of Veterans Affairs health care facility. Participants completed self
      report questionnaires including the CSQ-R and measures of disability, mood, and
      health. Confirmatory factor analysis (CFA) compared the 6-factor solution to
      models identified in other studies. The CFA indicated that the 6-factor solution
      of the CSQ-R proposed by Riley and Robinson (1997) is valid and has the best fit
      of all models tested when used with veterans. The results of the secondary
      correlational analyses were consistent with previous research indicating that
      coping self-statements and ignoring pain are adaptive pain coping strategies. Our
      findings support the psychometric soundness of the 6-factor CSQ-R when used with
      veterans with chronic pain. (PsycINFO Database Record

PMID- 29578742
TI  - Experimental effects of mindfulness inductions on self-regulation: Systematic
      review and meta-analysis.
AB  - Self-regulation is the control of aspects of the self to allow pursuit of long
      term goals, and it is proposed as a central pathway through which mindfulness may
      exert benefits on well-being. However, the effects of a single mindfulness
      induction on self-regulation are not clear, as there has been no comprehensive
      review of this evidence. The current review synthesized existing findings
      relating to the effect of a mindfulness induction delivered in a laboratory
      setting on measures of self-regulation. Twenty-seven studies were included and
      grouped according to 3 outcomes: regulation of experimentally induced negative
      affect (k = 15; meta-analysis), emotion-regulation strategies (k = 7) and
      executive functions (k = 9; narrative synthesis). A mindfulness induction was
      superior to comparison groups in enhancing the regulation of negative affect (d =
      -.28). Executive-function performance was enhanced only when the experimental
      design included an affect induction or when the outcome was sustained attention.
      The effect on emotion-regulation strategies was inconclusive, but with emerging
      evidence for an effect on rumination. Overall, the findings indicate that, in the
      form of an induction, mindfulness may have the most immediate effect on attention
      mechanisms rather than exerting cognitive changes in other domains, as are often
      reported outcomes of longer mindfulness training. Through effecting change in
      attention, emotion regulation of negative affect can be enhanced, and
      subsequently, executive-function performance more quickly restored. The
      interpretations of the findings are caveated with consideration of the low
      quality of many of the included study designs determined by the quality appraisal
      tool. (PsycINFO Database Record

PMID- 29578741
TI  - Dysregulated behavioral responses to hedonic probes among youth with depression
      histories and their high-risk siblings.
AB  - Affect dysregulation in response to rewarding stimuli has been proposed as a
      vulnerability factor for major depressive disorder (MDD). However, it remains
      unclear how affective behavioral dynamics may be altered among individuals who
      are at high risk for depression but not currently depressed. We examined the
      dynamics of affective facial behavior during hedonic probes among 3 groups of
      adolescents: remitted probands who had histories of childhood-onset MDD (n =
      187), never-depressed siblings of probands (high familial risk; n = 207), and
      healthy controls (n = 166). Participants' happy and sad facial expressions were
      coded during 3 hedonic laboratory tasks: receiving a preferred prize, describing
      a positive autobiographical memory, and watching a humorous film. Happy and sad
      behavioral dynamics were indexed by mean level- and time-dependent reactivity,
      variability (mean of the squared successive differences), and inertia
      (autocorrelation). Relative to controls, probands and siblings exhibited a more
      rapid decrease in happy behaviors, and probands exhibited higher inertia of sad
      behaviors during hedonic probes. Both probands and siblings exhibited lower
      inertia of sad behaviors while receiving a desired prize, which highlights the
      importance of context variation in testing hypotheses. Overall, our study
      provides new evidence that hedonic behavioral dysregulation, as reflected in
      dynamic facial behavior, may highlight depression vulnerability. (PsycINFO
      Database Record

PMID- 29578743
TI  - Stereotypes and prejudice affect the recognition of emotional body postures.
AB  - Most research on emotion recognition focuses on facial expressions. However,
      people communicate emotional information through bodily cues as well. Prior
      research on facial expressions has demonstrated that emotion recognition is
      modulated by top-down processes. Here, we tested whether this top-down modulation
      generalizes to the recognition of emotions from body postures. We report three
      studies demonstrating that stereotypes and prejudice about men and women may
      affect how fast people classify various emotional body postures. Our results
      suggest that gender cues activate gender associations, which affect the
      recognition of emotions from body postures in a top-down fashion. (PsycINFO
      Database Record

PMID- 29578744
TI  - The semantics of emotion in false memory.
AB  - The emotional valence of target information has been a centerpiece of recent
      false memory research, but in most experiments, it has been confounded with
      emotional arousal. We sought to clarify the results of such research by
      identifying a shared mathematical relation between valence and arousal ratings in
      commonly administered normed materials. That relation was then used to (a) decide
      whether arousal as well as valence influences false memory when they are
      confounded and to (b) determine whether semantic properties that are known to
      affect false memory covary with valence and arousal ratings. In Study 1, we
      identified a quadratic relation between valence and arousal ratings of words and
      pictures that has 2 key properties: Arousal increases more rapidly as function of
      negative valence than positive valence, and hence, a given level of negative
      valence is more arousing than the same level of positive valence. This quadratic
      function predicts that if arousal as well as valence affects false memory when
      they are confounded, false memory data must have certain fine-grained properties.
      In Study 2, those properties were absent from norming data for the Cornell
      Cortland Emotional Word Lists, indicating that valence but not arousal affects
      false memory in those norms. In Study 3, we tested fuzzy-trace theory's
      explanation of that pattern: that valence ratings are positively related to
      semantic properties that are known to increase false memory, but arousal ratings
      are not. (PsycINFO Database Record

PMID- 29578745
TI  - Boredom as a seeking state: Boredom prompts the pursuit of novel (even negative)
      experiences.
AB  - Building on functional models of emotion, we propose that boredom creates a
      seeking state that prompts people to explore new experiences, even if those
      experiences are hedonically negative. Specifically, as emotional responses fade,
      boredom motivates the pursuit of alternative experiences that differ from the
      experience that resulted in boredom. Participants who reported a higher degree of
      boredom after a neutral task were more likely to choose negative experiences
      (Study 1). Compared with a low-boredom condition, participants in a high-boredom
      condition desired novel experiences and, as a result of this desire, were more
      likely to choose novel negative experiences (Study 2). In Study 3, participants
      were made bored by positive or negative stimuli. Participants in the positive
      boredom conditions were more likely to choose a novel experience that was more
      negative; participants in the negative-boredom conditions were more likely to
      choose a novel experience that was more positive. These findings reveal that
      boredom motivates people to seek out novel experiences that elicit different
      (even more negative) feelings. (PsycINFO Database Record

PMID- 29578746
TI  - Visual features and perceptual context modulate attention towards evolutionarily
      relevant threatening stimuli: Electrophysiological evidence.
AB  - The snake detection hypothesis claims that predatory pressure from snakes has
      shaped the primate visual system, but we still know very little about how the
      brain processes evolutionarily important visual cues, and which factors are
      crucial for quick detection of snakes. We investigated how visual features
      modulate the electrophysiological markers of early attentional processes. In
      Experiment 1, we compared snake, rope, gun, and bird images to isolate the
      effects due to curvilinearity of the stimuli. The results showed that both snake
      and rope images elicited enhanced P1 and N1 event-related potential components as
      well as early posterior negativity (EPN). In Experiment 2, we studied whether
      nonthreatening curvilinear images (i.e., ropes) still elicit the enhanced
      electrophysiological responses when snake images are not presented as stimuli,
      and therefore the context does not provoke top-down attention to curvilinear
      shapes. Rope images still evoked an enhanced EPN, suggesting that curvilinear
      shapes are preferably captured by attentional processes. However, this effect was
      smaller than in Experiment 1, in which snake images were present. Thus, our
      results hint to the possibility that the perceptual context may interact with
      processing of shape information, drawing attention to curvilinear shapes when the
      presence of snakes is expectable. Furthermore, we observed that spatial frequency
      of the visual stimuli modulated especially the early electrophysiological
      responses, and decreased the differences between stimulus categories in EPN
      without completely eliminating them. The findings suggest that low-level and high
      level mechanisms interact to give an attentional priority to potentially
      threatening stimuli. (PsycINFO Database Record

PMID- 29578747
TI  - An experience sampling study examining the potential impact of a mindfulness
      based intervention on emotion differentiation.
AB  - Research has shown that how well people can differentiate between different
      emotional states is an essential requirement for adaptive emotion regulation.
      People with low levels of emotion differentiation tend to be more vulnerable to
      develop emotional disorders. Although we know quite a lot about the correlates of
      emotion differentiation, research on factors or interventions which could improve
      emotion differentiation skills is scarce. Here, we hypothesize, and study
      empirically, whether a mindfulness-based intervention (MBI) may impact the
      differentiation of negative and positive emotions. A within-subjects pre-, post-,
      and follow-up design involving experience sampling was used. At each phase
      participants reported their current emotions and mindfulness skills up to 40
      times across 4 consecutive days using smartphones. Multilevel modeling showed a
      significant improvement in negative emotion differentiation postintervention and
      at 4 months of follow-up, and a significant improvement in positive emotion
      differentiation at 4 months follow-up. The improvement in negative emotion
      differentiation, however, was no longer significant when controlling for levels
      of negative affect. A time-lagged mediation model showed that posttreatment
      changes in mindfulness skills mediated subsequent changes in negative emotion
      differentiation, also when controlling for levels of negative affect. These
      results suggest that MBI is a promising approach to improve people's emotion
      differentiation skills. (PsycINFO Database Record

PMID- 29578748
TI  - Negative emotionality across diagnostic models: RDoC, DSM-5 Section III, and FFM.
AB  - The research domain criteria (RDoC) were established in an effort to explore
      underlying dimensions that cut across many existing disorders and to provide an
      alternative to the Diagnostic and Statistical Manual of Mental Disorders, Fifth
      Edition (DSM-5). One purpose of the present study was to suggest a potential
      alignment of RDoC negative valence with 2 other dimensional models of negative
      emotionality: five-factor model (FFM) neuroticism and the DSM-5 Section III
      negative affectivity. A second purpose of the study, though, was to compare their
      coverage of negative emotionality, more specifically with respect to affective
      instability. Participants were adult community residents (N = 90) currently in
      mental health treatment. Participants received self-report measures of RDoC
      negative valence, FFM neuroticism, and DSM-5 Section III negative affectivity,
      along with measures of affective instability, borderline personality disorder,
      and impairment. Findings suggested that RDoC negative valence is commensurate
      with FFM neuroticism and DSM-5 Section III negative affectivity, and it would be
      beneficial if it was expanded to include affective instability. (PsycINFO
      Database Record

PMID- 29578750
TI  - Operative Management of Acute Triceps Tendon Ruptures: Review of 184 Cases.
AB  - BACKGROUND: Distal triceps tendon ruptures are rare. The authors present a series
      of 184 surgically treated, acute, traumatic triceps tendon avulsions and compare
      the complications between those treated with anchors (A) versus transosseous (TO)
      suture repair. HYPOTHESIS: No difference exists in the retear rate between TO and
      A repairs. Study Designed: Cohort study; Level of evidence, 3. METHODS: All
      patients who underwent an open primary repair of a traumatic triceps tendon
      avulsion within 90 days of injury, between 2007 and 2015, were retrospectively
      reviewed. Surgeries were performed within a multisurgeon (75 surgeons),
      multicenter (14 centers), community-based integrated health care system. Patient
      demographic information, type of repair, complications, and time from surgery to
      release from medical care were recorded. RESULTS: 184 triceps tears in 181
      patients met the inclusion criteria. The mean age was 49 years (range, 15-83
      years). There were 169 males. The most common mechanisms of injury were fall
      (56.5%) and weight lifting (19%). Mean time from injury to surgery was 19 days
      (range, 1-90 days); in 74.5% of cases, surgery was performed in 3 weeks or less.
      There were 105 TO and 73 A repairs. No significant difference was found between
      the two groups in the mean age ( P = .18), sex ( P = .51), completeness of tears
      ( P = .74), tourniquet time ( P = .455), and prevalence of smokers ( P = .64).
      Significant differences were noted between TO and A repairs in terms of
      reruptures (6.7% vs 0%, respectively; P = .0244), overall reoperation rate (9.5%
      vs 1.4%; P = .026), and release from medical care (4.3 vs 3.4 months; P = .0014),
      but no difference was seen in infection rate (3.8% vs 0%; P = .092). No
      difference was noted in release from medical care in patients who underwent
      surgery 3 weeks or less after injury compared with those undergoing surgery more
      than 3 weeks after injury (3.90 vs 4.09 months, respectively; P = .911).
      CONCLUSION: Primary repair of triceps ruptures with TO fixation has a
      significantly higher rerupture rate, higher reoperation rate, and longer release
      from medical care than does repair with A fixation. Implementation of suture
      anchors in triceps repairs offers a lower complication rate and earlier release
      from medical care.

PMID- 29578749
TI  - Positive End-Expiratory Pressure Ventilation Induces Longitudinal Atrophy in
      Diaphragm Fibers.
AB  - RATIONALE: Diaphragm weakness in critically ill patients prolongs ventilator
      dependency and duration of hospital stay and increases mortality and healthcare
      costs. The mechanisms underlying diaphragm weakness include cross-sectional fiber
      atrophy and contractile protein dysfunction, but whether additional mechanisms
      are at play is unknown. OBJECTIVES: To test the hypothesis that mechanical
      ventilation with positive end-expiratory pressure (PEEP) induces longitudinal
      atrophy by displacing the diaphragm in the caudal direction and reducing the
      length of fibers. METHODS: We studied structure and function of diaphragm fibers
      of mechanically ventilated critically ill patients and mechanically ventilated
      rats with normal and increased titin compliance. MEASUREMENTS AND MAIN RESULTS:
      PEEP causes a caudal movement of the diaphragm, both in critically ill patients
      and in rats, and this caudal movement reduces fiber length. Diaphragm fibers of
      18-hour mechanically ventilated rats (PEEP of 2.5 cm H2O) adapt to the reduced
      length by absorbing serially linked sarcomeres, the smallest contractile units in
      muscle (i.e., longitudinal atrophy). Increasing the compliance of titin molecules
      reduces longitudinal atrophy. CONCLUSIONS: Mechanical ventilation with PEEP
      results in longitudinal atrophy of diaphragm fibers, a response that is modulated
      by the elasticity of the giant sarcomeric protein titin. We postulate that
      longitudinal atrophy, in concert with the aforementioned cross-sectional atrophy,
      hampers spontaneous breathing trials in critically ill patients: during these
      efforts, end-expiratory lung volume is reduced, and the shortened diaphragm
      fibers are stretched to excessive sarcomere lengths. At these lengths, muscle
      fibers generate less force, and diaphragm weakness ensues.

PMID- 29578751
TI  - In Vitro and In Vivo Performance of Tissue-Engineered Tendons for Anterior
      Cruciate Ligament Reconstruction.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is the current
      standard of care for ACL tears. However, the results are not consistently
      successful; autografts or allografts have certain disadvantages; and synthetic
      grafts have had poor clinical results. PURPOSE: To determine if recellularization
      of decellularized tendons combined with mechanical stimulation in a bioreactor
      could replicate the mechanical properties of the native ACL and be successfully
      used for ACL reconstruction in vivo. STUDY DESIGN: Controlled laboratory study.
      METHODS: Porcine tibialis tendons were decellularized and then recellularized
      with human adult bone marrow-derived stem cells. Tendons were cultured in a
      tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To
      reproduce mechanical stresses similar to those experienced by the ACL within the
      knee joint, the tendons were subjected to simultaneous tension and torsion in the
      bioreactor. Expression of tendon-specific genes and newly synthesized collagen
      and glycosaminoglycan were used to quantify the efficacy of recellularization and
      dynamic bioreactor culture. The ultimate tensile load to failure and stiffness of
      recellularized constructs were measured after dynamic stimulation. Finally, the
      tissue-engineered tendons were used to reconstruct the ACL in 24 pigs, and
      ultimate tensile load to failure and stiffness were assessed after 3 months.
      RESULTS: Dynamic bioreactor culture significantly increased the expression of
      tendon-specific genes, the quantity of newly synthesized collagen and
      glycosaminoglycan, and the ultimate tensile load and stiffness of recellularized
      tendons. After in vivo reconstruction, the ultimate tensile load and stiffness of
      the tissue-engineered tendons increased significantly up to 3 months after
      surgery and were within 80% of the ultimate tensile load of the natural ACL.
      CONCLUSION: This translational study indicates that recellularization and dynamic
      mechanical stimuli can significantly enhance matrix synthesis and ultimate
      tensile load of decellularized porcine tibialis tendons. This approach to tissue
      engineering can be very useful for ACL reconstruction and may overcome some of
      the disadvantages of autografts and allografts. CLINICAL RELEVANCE: Dynamic
      bioreactor cultivation of tissue-engineered tendons may overcome the limitations
      of autografts and allografts.

PMID- 29578752
TI  - Assessing Asthma Medication Responses in U.S. Minority Children by Whole-Genome
      Sequencing.

PMID- 29578753
TI  - Can Mother-Daughter Communication Buffer Adolescent Risk for Mental Health
      Problems Associated With Maternal Depressive Symptoms?
AB  - The current study sought to test whether higher quality mother-daughter
      communication would buffer associations between maternal depressive symptoms and
      girls' internalizing and externalizing psychopathology symptoms among urban
      African American girls across a 12-month period. One hundred ninety-four
      treatment-seeking urban African American adolescent girls, ages 12-16, and their
      mothers participated in the study. Every 6 months (for up to 3 assessments),
      daughters reported on their internalizing and externalizing symptoms, mothers
      reported on their depressive symptoms, and both mothers and daughters reported on
      the quality of their dyadic communication. Daughters additionally reported on the
      extent to which they felt accepted by their mothers at each assessment. Results
      of multilevel modeling revealed that quality of communication significantly
      interacted with maternal depressive symptoms to predict externalizing and
      internalizing symptoms in daughters, such that the risk associated with maternal
      depressive symptoms was fully buffered for daughters in high-quality
      communication dyads. Secondary analyses demonstrated that these patterns of
      results were not accounted for by higher levels of social status or maternal
      acceptance. Drawing on a vulnerable and understudied population of urban African
      American adolescent girls, this work suggests that family communication may
      contribute to important intergenerational psychopathology transmission processes,
      above and beyond more general features of the family environment.

PMID- 29578755
TI  - Exploring Cost Constraints on Stem Elongation in Plants Using Phenotypic
      Manipulation.

PMID- 29578754
TI  - Auditory Task Irrelevance: A Basis for Inattentional Deafness.
AB  - Objective This study investigates the neural basis of inattentional deafness,
      which could result from task irrelevance in the auditory modality. Background
      Humans can fail to respond to auditory alarms under high workload situations.
      This failure, termed inattentional deafness, is often attributed to high workload
      in the visual modality, which reduces one's capacity for information processing.
      Besides this, our capacity for processing auditory information could also be
      selectively diminished if there is no obvious task relevance in the auditory
      channel. This could be another contributing factor given the rarity of auditory
      warnings. Method Forty-eight participants performed a visuomotor tracking task
      while auditory stimuli were presented: a frequent pure tone, an infrequent pure
      tone, and infrequent environmental sounds. Participants were required either to
      respond to the presentation of the infrequent pure tone (auditory task-relevant)
      or not (auditory task-irrelevant). We recorded and compared the event-related
      potentials (ERPs) that were generated by environmental sounds, which were always
      task-irrelevant for both groups. These ERPs served as an index for our
      participants' awareness of the task-irrelevant auditory scene. Results
      Manipulation of auditory task relevance influenced the brain's response to task
      irrelevant environmental sounds. Specifically, the late novelty-P3 to irrelevant
      environmental sounds, which underlies working memory updating, was found to be
      selectively enhanced by auditory task relevance independent of visuomotor
      workload. Conclusion Task irrelevance in the auditory modality selectively
      reduces our brain's responses to unexpected and irrelevant sounds regardless of
      visuomotor workload. Application Presenting relevant auditory information more
      often could mitigate the risk of inattentional deafness.

PMID- 29578756
TI  - Quantitative Trait Loci for Early- and Late-Developing Skull Characters in Mice:
      A Test of the Genetic Independence Model of Morphological Integration.
AB  - Quantitative genetical theory suggests that characters existing in
      developmentally or functionally integrated groups are expected to be genetically
      correlated because they share a common inheritance. The genetic independence
      model for the cause of this genetic integration predicts that pleiotropic effects
      of single genes are mostly restricted to the characters in these integrated
      groups. We tested this model by estimating the additive and dominance effects of
      quantitative trait loci (QTLs) affecting early- (cranial vault) and late
      developing (face) skeletal characters in F2 house mice originally derived from a
      cross of the Large and Small inbred strains. Interval mapping procedures were
      used that resulted in the identification of 26 QTLs on 17 of the 19 autosomes
      that significantly affected these characters. Additive, but not dominance,
      genotypic effects of many of these QTLs predominantly affected either the cranial
      vault or face characters, which supports the genetic independence model. Only two
      QTLs had positive pleiotropic effects on one group of characters but negative
      pleiotropic effects on the other (antagonistic pleiotropy).

PMID- 29578757
TI  - The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.
AB  - House mice prefer mates genetically dissimilar at the major histocompatibility
      complex (MHC). The highly polymorphic MHC genes control immunological
      self/nonself recognition; therefore, this mating preference may function to
      provide "good genes" for an individual's offspring. However, the evidence for MHC
      dependent mating preferences is controversial, and its function remains unclear.
      Here we provide a critical review of the studies on MHC-dependent mating
      preferences in mice, sheep, and humans and the possible functions of this
      behavior. There are three adaptive hypotheses for MHC-dependent mating
      preferences. First, MHC-disassortative mating preferences produce MHC
      heterozygous offspring that may have enhanced immunocompetence. Although this
      hypothesis is not supported by tests of single parasites, MHC heterozygotes may
      be resistant to multiple parasites. Second, we propose that MHC-dependent mating
      preferences enable hosts to provide a "moving target" against rapidly evolving
      parasites that escape immune recognition (the Red Queen hypothesis). Such
      parasites are suspected to drive MHC diversity through rare-allele advantage.
      Thus, the two forms of parasite-mediated selection thought to drive MHC
      diversity, heterozygote and rare-allele advantage, will also favor MHC-dependent
      mating preferences. Finally, MHC-dependent mating preferences may also function
      to avoid inbreeding; a hypothesis consistent with other evidence that MHC genes
      play a role in kin recognition.

PMID- 29578758
TI  - Plumage Reflectance and the Objective Assessment of Avian Sexual Dichromatism.
AB  - Assessment of color using human vision (or standards based thereon) is central to
      tests of many evolutionary hypotheses. Yet fundamental differences in color
      vision between humans and other animals call this approach into question. Here we
      use techniques for objectively assessing color patterns that avoid reliance on
      species-specific (e.g., human) perception. Reflectance spectra are the invariant
      features that we expect the animal's color cognition to have evolved to extract.
      We performed multivariate analyses on principal components derived from >2,600
      reflectance spectra (300-720 nm) sampled in a stratified random design from
      different body regions of male and female starlings in breeding plumage.
      Starlings possess spatially complex plumage patterns and extensive areas of
      iridescence. Our study revealed previously unnoticed sex differences in plumage
      coloration and the nature of iridescent and noniridescent sex differences. Sex
      differences occurred in some body regions but not others, were more pronounced at
      some wavelengths (both ultraviolet and human visible), and involved differences
      in mean reflectance and spectral shape. Discriminant analysis based on principal
      components were sufficient to sex correctly 100% of our sample. If hidden sexual
      dichromatism is widespread, then it has important implications for
      classifications of animals as mono- or dimorphic and for taxonomic and
      conservation purposes.

PMID- 29578759
TI  - Does Host Self-Regulation Increase the Likelihood of Insect-Pathogen Population
      Cycles?

PMID- 29578760
TI  - How Habitat Edges Change Species Interactions.
AB  - Traditionally, ecologists interested in habitat edges have focused on edge
      related gradients in patterns of species richness or abiotic variables. Here,
      however, we take a different perspective, attempting to synthesize recent
      empirical results concerning the effects of habitat edges on population dynamics
      with contemporary theoretical developments to outline the ways in which species
      interactions, and the dynamics of the communities in which they are embedded, can
      be changed by habitat edges. We find a striking convergence between empirical
      notions of a patch's core area and analytical results from partial differential
      equation models. A review of both empirical and theoretical studies suggests four
      general classes of mechanisms through which habitat edges can have similar
      impacts on dissimilar types of species interactions. Specifically, we focus on
      edges' roles as dispersal barriers or filters, edges' influences on mortality,
      edges' involvement in spatial subsidies (in which dispersers' intrapatch impacts
      are maintained by their activities in other habitats), and edges' roles as
      generators of novel interactions. For each class of edge-mediated effects, we
      provide examples of how one can use spatial modeling to address the relevant
      questions on these topics, which together form a key link between community
      dynamics and landscape structure.

PMID- 29578761
TI  - Corridor Use Predicted from Behaviors at Habitat Boundaries.
AB  - Through empirical studies and simulation, I demonstrate how simple behaviors can
      be used in lieu of detailed dispersal studies to predict the effects of corridors
      on interpatch movements. Movement paths of three butterfly species were measured
      in large (1.64 ha) experimental patches of open habitat, some of which were
      connected by corridors. Butterflies that "reflected" off boundaries between open
      patches and the surrounding forest also emigrated from patches through corridors
      at rates higher than expected from random movement. This was observed for two
      open-habitat species, Eurema nicippe and Phoebis sennae; however, edges and
      corridors had no effect on a habitat generalist, Papilio troilus. Behaviorally
      based simulation models, which departed from correlated random walks only at
      habitat boundaries, predicted that corridors increase interpatch movement rates
      of both open-habitat species. Models also predicted that corridors have
      proportionately greater effects as corridor width increases, that movement rates
      increase before leveling off as corridor width increases, and that corridor
      effects decrease as patch size increases. This study suggests that corridors
      direct movements of habitat-restricted species and that local behaviors may be
      used to predict the conservation potential of corridors in fragmented landscapes.

PMID- 29578762
TI  - Males Feeding Females during Incubation. I. Required by Microclimate or
      Constrained by Nest Predation?
AB  - Nest attentiveness (percentage of time spent on the nest) during incubation
      represents a parent-offspring conflict; incubating birds must balance a trade-off
      between caring for embryos by staying on the nest versus caring for themselves by
      getting off the nest to forage. For species in which females are the sole
      incubator, males can potentially affect this trade-off and increase nest
      attentiveness by feeding incubating females on the nest (incubation feeding).
      Increased nest attentiveness may be required when local microclimate conditions
      are harsh and thereby require greater incubation feeding (microclimate
      hypothesis). Alternatively, incubation feeding may be constrained by risk of
      attracting nest predators (nest predation hypothesis), which in turn may
      constrain female nest attentiveness because of energy limitation. We show that
      incubation feeding rates are much greater among cavity-nesting than among
      coexisting open-nesting birds. Under the microclimate hypothesis, the greater
      incubation feeding rates of cavity-nesting birds generate the prediction that
      microclimate should be harsher than for open-nesting birds. Our results reject
      this hypothesis because we found the opposite pattern; cavity-nesting birds
      experienced more moderate (less variable) microclimates that were less often
      below temperatures (i.e., 16 degrees C) that can negatively impact eggs compared
      with open-nesting species. In contrast, incubation feeding rates were highly
      negatively correlated with nest predation both within and between the two nest
      types, supporting the nest predation hypothesis. Incubation feeding in turn was
      positively correlated with nest attentiveness. Thus, nest predation may
      indirectly affect female incubation behavior by directly affecting incubation
      feeding by the male.

PMID- 29578763
TI  - The Adaptive Dynamics of Consumer Choice.
AB  - This article uses mathematical models to investigate the consequences of
      noninstantaneous choice between two prey types by a predator. The models are
      characterized by three features: sustained cycles in predator and prey population
      sizes, a trade-off between the predator's consumption rates of the two prey and
      adaptive adjustment of the consumption rates at a rate proportional to the change
      in predator fitness per unit change in consumption rates. Adaptive adjustment of
      consumption rates frequently prevents the system from achieving an ideal free
      distribution of predator foraging effort and frequently results in chaotic
      dynamics or alternative attractors. The process of switching to consume the more
      common prey can reduce the minimum density of one or both prey. These phenomena
      occur for a variety of different models, including models in which both prey are
      in the same or in distinct habitats. An ideal free distribution can often be
      attained by adding prey refuges or immigration, provided these have a large
      enough effect on the dynamics of the system. The dynamics of switching can be
      important in determining indirect interactions between prey species and other
      aspects of food web dynamics.

PMID- 29578764
TI  - The Implications of Experimental Design for Biodiversity Manipulations.
AB  - I report a simulation study that tested the ability of a variety of experimental
      designs to achieve two fundamental goals: (1) to determine the association
      between loss of biological diversity and responses such as ecosystem functioning
      and (2) to determine which components of biodiversity, such as number of species,
      functional diversity, or a keystone species, were most responsible for that
      association. For the goal of reliably detecting an overall association, all
      designs I tested performed well and were unlikely to misidentify predominant
      patterns. Thus, this study affirms the common conclusion of many published
      biodiversity experiments that loss of biological diversity is often associated
      with a reduction in ecosystem functioning. However, for the goal of identifying
      the components of biodiversity that are most responsible for the effects, designs
      differed markedly. Some designs performed well in detecting number-of-species
      effects but poorly in detecting effects of unique species or functional groups.
      No design tested was able to discriminate both numeric effects and compositional
      effects in all situations. Thus, this study demonstrates that interpreting
      results about mechanisms from biodiversity experiments will be critically
      dependent on an experiment's design.

PMID- 29578765
TI  - The Evolution of Search Modes: Ecological versus Phylogenetic Perspectives.
AB  - Both theoretical and empirical studies, many of them on lizards, suggest that
      foraging behaviors often take one of two forms, sometimes called "modes": active
      search or sedentary ambush. I tested this by expanding the database on lizard
      foraging behaviors and testing for the existence of modality in this much larger
      database. My findings did not support the validity of some previous analyses.
      Greatly expanded lizard data did not show a bimodal distribution of foraging
      behaviors. Phylogeny, however, was a strong predictor of behavior. One clade,
      Autarchoglossa, was characterized by a wide range of foraging behaviors, but
      closely related species tended to exhibit similar behaviors. Two other clades,
      Iguania and Gekkota, retain the ancestral sedentary behavior. This phylogenetic
      trend, combined with phylogenetically biased sampling, may have been responsible
      for the appearance of bimodality in previous studies. Thus, bimodality of search
      modes is rejected. Some previous generalizations regarding correlates of foraging
      "mode" need to be reevaluated in this light.

PMID- 29578766
TI  - Diversity in Relation to Body Size in Mammals: A Comparative Study.
AB  - A wide variety of higher taxa show right-skewed frequency distributions of
      species' body sizes, and a negative relationship is often found between the
      number of species within a taxonomic group and its mean size. These patterns may
      arise from essentially random cladogenesis and extinction, from the tendency of
      organisms to anagenetically track a relatively small optimal size, or from high
      rates of cladogenesis at relatively small sizes. We used body mass data for about
      65% of the world's mammal species to test the predictions of these alternative
      mechanisms. Using phylogenetically independent contrasts to control for phylogeny
      and clade age, we found that although size does not appear to be a general
      correlate of diversity, large radiations of species do tend to be small bodied.
      This pattern seems most consistent with the hypothesis that the number of niches
      is potentially greatest for small-bodied taxa.

PMID- 29578768
TI  - A Comment on In-Group/Out-Group Comparisons for Fluctuating Asymmetry Based on
      Trait Values from the Left or Right Sides of an Individual.

PMID- 29578767
TI  - Effect of Prey Heterogeneity on the Response of a Model Food Chain to Resource
      Enrichment.
AB  - We demonstrated that the presence of invulnerable prey can result in a shift in
      the balance between top-down and bottom-up control of a model food chain. Our
      model food chain consisted of the bacterium Escherichia coli and the
      bacteriophage T4 (a virus that feeds on E. coli) in chemostats supplied with
      different concentrations of glucose. The E. coli population consisted of
      individuals that were susceptible to predation by T4 ("edible" E. coli) and
      individuals that were resistant to predation by T4 ("inedible" E. coli). The
      equilibrium density of a heterogeneous prey population (consisting of edible and
      inedible E. coli) increased strongly in response to an enrichment of its
      resources. This response consisted of an increase in the inedible fraction of the
      prey population but no change in the edible fraction. In contrast, a homogeneous
      prey population (edible E. coli only) increased only marginally. The equilibrium
      density of the predator population (bacteriophage T4) did not significantly
      increase in response to enrichment when its prey were heterogeneous, but it
      increased strongly when its prey were homogeneous.

PMID- 29578769
TI  - Top-Down Control of Cyanobacteria: A Theoretical Analysis.
AB  - Field patterns and experimental results suggest that the effect of zooplankton
      grazing on the abundance of large colonial cyanobacteria may differ strongly from
      case to case. In this article we present an extensive analysis of a model that
      describes the competition between cyanobacteria of the Oscillatoria group and
      green algae exploited by Daphnia. In particular, we study the response of the
      model to changes in the nutrient concentration and predation by zooplanktivorous
      fish. The analysis is repeated for an array of different assumptions on the
      nutritional value of cyanobacteria and selectivity of zooplankton grazing. When
      fish predation pressure is so high that Daphnia density is negligible, there is
      competitive exclusion between the two primary producers, and over a range of
      nutrient levels, there are two alternative attractors: one with only
      cyanobacteria and one with only green algae. When fish predation pressure is
      lower, zooplankton becomes important, and if grazing by these animals is
      sufficiently selective, this may cause a third attractor on which Daphnia,
      cyanobacteria, and algae coexist. This "mixed" attractor may be stationary,
      oscillatory, or chaotic. Depending on the nutrient level, the nutritional value
      of cyanobacteria, and the selectivity of zooplankton, cyanobacterial dominance
      may be either induced or eliminated in response to reduced fish predation. This
      is well in line with the confusing array of field studies and experimental
      results.

PMID- 29578770
TI  - Erratum.

PMID- 29578771
TI  - The Temporal Coherence of Zooplankton Population Abundances in Neighboring North
      Temperate Lakes.
AB  - We investigated the temporal coherence (i.e., the correlation or synchrony
      between time series) of annual abundances among populations of freshwater
      zooplankton in eight lakes in Ontario, Canada, from 1980 to 1992. We estimated
      temporal coherence using the intraclass correlation coefficient (ri). While
      values of ri were relatively low among comparisons of all eight lakes, they were
      statistically significant for three of the seven common cladoceran and copepod
      taxa (Bosmina longirostris, Leptodiaptomus minutus, and Mesocyclops edax). These
      significant positive correlations imply that a portion of the interannual
      variation in abundance was produced by factors operating on a scale larger than
      the individual lake catchments. Because the eight-lake analysis might obscure
      strong, but conflicting, patterns among lakes in the region, we identified
      homogeneous and temporally coherent subsets of lakes for each species using an
      exploratory stepwise deletion procedure. The resultant homogeneous subsets
      exhibited much greater temporal coherence, accounting for 47% (Eubosmina) to 84%
      (Leptodiaptomus) of the interannual variation in abundance. Our results suggest
      that the factors affecting annual variation in zooplankton abundance must be
      sought both within lakes and beyond their watersheds.

PMID- 29578772
TI  - Sex-Ratio Selection in Species with Helpers at the Nest: The Repayment Model
      Revisited.
AB  - We reexamine the theoretical and empirical basis for the "repayment model" of
      Emlen, Emlen, and Levin, which predicts that the overall sex ratio of offspring
      in cooperative-breeding species with helpers at the nest should be biased toward
      the more helpful sex. We conclude that in theory the model may yield a biased sex
      ratio but only under restricted conditions that are unlikely to be met in most
      populations. In those cases where the model is potentially applicable, estimates
      of both direct and indirect fitness of sons and daughters are necessary in order
      to avoid double accounting. As a result, extensive demographic data are required
      to determine the expected sex-ratio bias. Empirically, none of the three examples
      originally suggested as supporting the repayment model withstand critical
      scrutiny. Using long-term demographic data from two populations of one of these
      species, the red-cockaded woodpecker (Picoides borealis), we determine that the
      model predicts a biased sex ratio not observed in the data. This suggests that
      confounding factors may counter the sex-ratio bias predicted by the model, that
      the extensive empirical data available for this species may be insufficient to
      test the model, or that there are as yet unknown theoretical difficulties with
      the model. Finally, we discuss the recently reported case of the Seychelles
      warbler (Acrocephalus sechellensis). The extraordinarily biased sex ratios
      reported in this species are in accord with those predicted by the model when
      applied at the scale of individual groups but not at the population level.
      Additional empirical work is necessary to determine what, if any, the generality
      and usefulness of the repayment model may be.

PMID- 29578773
TI  - Reptile Extinctions on Land-Bridge Islands: Life-History Attributes and
      Vulnerability to Extinction.
AB  - One of the central questions of conservation biology is what life-history traits
      render a species prone to extinction. We addressed this problem by calculating
      extinction rates for 35 species of turtles and squamates (lizards and snakes)
      occurring on 87 land-bridge islands in the Mediterranean Sea. We calculated
      extinction rates in two ways: first, by incorporating the known sequence of
      historical island separations and second by ignoring history and assuming that
      the islands became isolated simultaneously. The second procedure is simpler and
      more frequently used in the literature and produces estimates of extinction rates
      that are similar to the first, more complex procedure. We then determined the
      relationship between extinction rates (calculated using both methods) and body
      mass, longevity, habitat specialization, and population abundance using two
      methods: first, by accounting for the phylogenetic relationships among species
      and, second, by ignoring them. Only population abundance and habitat
      specialization explained a significant amount of the observed variation in
      species extinction rates. Body mass itself did not explain variation in
      extinction rates, although it was strongly correlated with abundance. These
      conclusions were obtained using both procedures for calculating extinction rates
      and both procedures for correlating extinction rates with life-history traits.

PMID- 29578774
TI  - Greater Static Anterior Tibial Subluxation of the Lateral Compartment After an
      Acute Anterior Cruciate Ligament Injury Is Associated With an Increased Posterior
      Tibial Slope.
AB  - BACKGROUND: Static anterior tibial subluxation of the lateral compartment after
      an anterior cruciate ligament (ACL) injury highlights an increased anterior
      position of the tibia relative to the femur. However, the precise cause of this
      phenomenon is not entirely clear. Recently, an increased posterior tibial slope
      (PTS) has been identified as an independent risk factor for noncontact ACL
      injuries. HYPOTHESIS: An increased PTS is associated with an increased anterior
      position of the lateral compartment of the tibia relative to the femur after
      acute ACL injuries. STUDY DESIGN: Case-control study; Level of evidence, 3.
      METHODS: From March 2016 to March 2017, a total of 154 patients with clinically
      diagnosed noncontact ACL injuries who underwent primary ACL reconstruction were
      retrospectively analyzed. Static anterior subluxation of the lateral compartment
      relative to the lateral femoral condyle was measured on preoperative magnetic
      resonance imaging. Among them, 23 patients (study group) who demonstrated >=6-mm
      anterior subluxation of the lateral compartment were matched in a 1:1 fashion to
      23 control participants (control group), who showed <6-mm anterior subluxation of
      the lateral compartment. The PTS was measured on routinely available preoperative
      weightbearing lateral knee radiographs. Predictors of increased (>=6 mm) static
      anterior subluxation of the lateral compartment, including body mass index (BMI),
      PTS, injuries to the anterolateral ligament (ALL), and concomitant lateral
      meniscal lesions, were assessed by multivariable conditional logistic regression
      analysis. RESULTS: The mean PTS in the study group was 15.4 degrees , which was
      significantly larger than that in the control group (8.8 degrees ) ( P < .001).
      In addition, an abnormal degree of PTS (>=10.0 degrees ) was determined to be an
      independent risk factor (odds ratio, 8.0 [95% CI, 2.7-29.2]; P < .001) associated
      with >=6-mm anterior subluxation of the lateral compartment after acute ACL
      injuries. However, BMI, presence of concomitant lateral meniscal lesions, and
      presence of ALL ruptures were not. CONCLUSION: An increased PTS was identified to
      be an independent anatomic risk factor of increased (>=6 mm) anterior subluxation
      of the lateral compartment in acute noncontact ACL injuries. For patients with
      obviously increased anterior tibial subluxation of the lateral compartment after
      ACL injuries, the PTS should be measured.

PMID- 29578775
TI  - Migration, Virulence, and the Geographic Mosaic of Adaptation by Parasites.
AB  - The geographic mosaic theory of coevolution is predicated on structured
      populations of interacting species where gene flow and the force of selection can
      vary among populations, leading to a mosaic of traits in space. Here, I briefly
      review some recent studies of adaptation by a sterilizing parasite to structured
      populations of a freshwater snail. The results show geographic structure as
      expected under the geographic mosaic model. I then consider the effects of
      virulence and migration on local adaptation by parasites using a computer
      simulation. The results suggest that high virulence and low migration contribute
      to the strength of local adaptation by parasites. Highly virulent parasites
      showed adaptation to local hosts for migration rates of up to 10% of the
      population per generation. In addition, because of the dynamic nature of host
      parasite coevolution, the magnitude of local adaptation fluctuates over time.
      During some points in the cycle, parasites may be no more effective at infecting
      individuals from local host populations, even though they would be shown to be
      locally adapted if examined over enough generations. Contrary to expectation,
      parasite local adaptation was not affected by giving the parasite a longer
      generation time than the host, but differences in local selection intensities had
      a dramatic effect.

PMID- 29578776
TI  - Mutualism in Metapopulations of Legumes and Rhizobia.
AB  - Coevolution in mutualisms may result in a stable mosaic pattern of spatial
      differentiation, with regions occupied by different coadapted pairs of mutualists
      each being resistant to invasion by organisms with alternative phenotypes. The
      evolution of geographic mosaic patterns was analyzed for symbioses of legume
      plants and root-nodule bacteria (rhizobia), where plants are commonly polymorphic
      for genes affecting mutualism specificity. Typically, some alleles confer broad
      compatibility, and others restrict the set of bacterial genotypes accepted by
      plants as mutualist partners. Metapopulation simulation models with genetic
      assumptions matching the observed form of symbiotic specificity show that
      selection can generate a stable geographic mosaic if certain conditions are
      satisfied regarding competitive abilities, fitness benefits from mutualism, and
      migration rates. The structure of geographic variation in natural populations of
      the annual legume Amphicarpaea bracteata, together with patterns of variation in
      symbiotic fitness, is consistent with the interpretation that a mosaic pattern of
      differentiation may exist. Experimental and observational studies necessary to
      test more rigorously for mosaic distributions are outlined.

PMID- 29578777
TI  - Spatial and Temporal Patterns in Coevolving Plant and Pathogen Associations.
AB  - Spatial structuring is important in understanding the ecological and evolutionary
      dynamics of natural populations since local demes are rarely, if ever, completely
      isolated from neighboring demes. Plant host-pathogen interactions provide good
      examples of coevolutionary systems where both numerical and genetic dynamics have
      been explicitly investigated in a spatial context and where genes under selection
      can be unambiguously identified. In this article, we focus on long-term studies
      of several natural host-pathogen interactions that span a range of life histories
      and taxa. We use these studies to evaluate some predictions for numerical and
      genetic patterns at local and regional scales. Specifically, we examine the
      degree of among-population asynchrony in disease presence/absence and abundance,
      and the extent to which this is a function of isolation. For one host-pathogen
      interaction (Linum-Melampsora), we focus on whether there is local correspondence
      between resistance and virulence genes (as would be predicted by single
      population coevolutionary models) or whether such correspondence occurs at larger
      spatial scales. Finally, we discuss the implications of these studies with
      respect to the impact of host and pathogen life-history variation on the spatial
      scale of coevolutionary interactions. Understanding coevolutionary interactions
      in nature requires a multidisciplinary approach, including long-term empirical
      studies of multiple populations and computer modeling.

PMID- 29578778
TI  - Geographic Patterns in the Evolution of Resistance and Virulence in Drosophila
      and Its Parasitoids.
AB  - Many insects are attacked by internal parasitoids against which they mount a
      largely cellular immunological defense. The resistance of a host and the
      virulence of a parasitoid determine which species survives after parasitism.
      Drosophila is parasitized by several hymenopterous parasitoids, especially those
      in the genera Asobara and Leptopilina. Geographic patterns have been found in
      parasitoid virulence and host resistance, the clearest of which is a cline in
      Asobara tabida virulence from the north (low) to the south (high) of Europe.
      Drosophila melanogaster resistance is highest in central-southern Europe and
      lower elsewhere. We review and interpret these patterns in the light of recent
      experimental and theoretical studies of the evolution and coevolution of these
      traits. We find no evidence for genotype-specific virulence and defense, which
      makes "Red Queen"-type coevolution unlikely. The most important explanation for
      the patterns is geographic differences in host-parasitoid community structure.
      Asobara tabida virulence is positively correlated with the resistance of its main
      hosts, and there is more limited evidence that D. melanogaster resistance is
      influenced by the virulence of its parasitoids. We critically appraise whether
      the evidence available so far supports a coevolutionary explanation for the
      levels of these traits.

PMID- 29578779
TI  - The Selection Mosaic and Diversifying Coevolution between Crossbills and
      Lodgepole Pine.
AB  - Asymmetrical competition determines which of two seed predators drives the
      evolution of lodgepole pine (Pinus contorta ssp. latifolia) cones. Red squirrels
      (Tamiasciurus hudsonicus) are effective preemptive competitors in lodgepole pine
      forests so that red crossbills (Loxia curvirostra) are uncommon and selection
      from Tamiasciurus drives cone evolution. When Tamiasciurus are absent, crossbills
      increase in abundance and coevolve in an evolutionary arms race with pine.
      Similarly, Tamiasciurus alters the evolutionary trajectories of large-seeded
      pines, many of which rely on birds (Corvidae) for their seed dispersal.
      Populations therefore exhibit a selection mosaic with coevolutionary hot spots.
      In the coevolutionary hot spots, divergent selection on crossbills potentially
      leads to reproductive isolation and speciation. This results in a subsequent
      reduction in the geographic mosaic but diversifies the adaptive landscape on
      which crossbills have radiated. Thus, divergent selection is a double-edged
      sword. Divergent selection is critical in creating a selection mosaic but erodes
      the selection mosaic when it promotes reproductive isolation and speciation.

PMID- 29578780
TI  - A Comparison of the Taxonomic Richness of Vascular Plants in China and the United
      States.
AB  - Numbers of taxa at the level of order, family, genus, and species were tabulated
      for 12 subclass-level taxonomic groups of vascular plants in the floras of China
      and the United States. Analysis of these data showed that the flora of China is
      significantly more diverse than that of the United States. Furthermore, the
      difference in diversity arises at and below the level of genera. Finally, the
      euasterids II and Caryophyllidae are exceptions to the general trend in being
      more diverse in the United States. As a result, the floras of China and the
      United States are different nonrandom samples of the floras of the North
      Temperate Zone and the world. Phylogenetically older groups have a larger
      proportion of genera shared between China and the United States and also tend to
      have larger proportions of taxa belonging to genera with tropical affinities. The
      two subclass-level groups that are more diverse in the United States have
      primarily temperate affinities and are relatively young phylogenetically. We
      conclude that the patterns of diversity of Chinese and U.S. vascular plants have
      been influenced by the longer and more open access of temperate eastern Asia to
      tropical regions, the presence in southern China of a larger area of subtropical
      climate with complex topography, and the reduced impact of late Tertiary climate
      cooling in eastern Asia compared to North America. The greatest differences in
      diversity occur among older groups having stronger tropical affinities and,
      perhaps, originating in eastern Asia. In the North American flora, these groups
      appear to be disproportionately small relicts of a formerly widespread
      "boreotropical flora" that was relatively homogeneous at the genus level across
      the Bering Land Bridge between eastern Asia and North America. Groups that arose
      and diversified later, and that have fewer genera in common between Asian and
      North American floras, particularly the euasterids II, were better adapted to the
      cooler and drier climates of the Neogene temperate latitudes and evidently were
      relatively unaffected by late Neogene glaciations. These groups are thus as
      diverse, or more diverse, in North America as in eastern Asia. Understanding the
      relative diversity of two regions requires an appreciation of the historical
      development of the floras in the context of large-scale processes and events.

PMID- 29578781
TI  - Increasing Genomic Complexity by Gene Duplication and the Origin of Vertebrates.
AB  - Prevailing hypotheses concerning the origin of the vertebrate genome postulate
      successive genome duplications before the origin of fishes or tetrapods. These
      hypotheses predict episodic expansion of gene families early in vertebrate
      evolution (mostly before the origin of fishes), tetralogous relationships between
      gene copies samples from invertebrates and vertebrates, and gene family trees
      with symmetrical shapes. None of these predictions were evident from a
      phylogenetic analysis of 35 gene families. Overall, the results do not refute the
      hypothesis that gene family evolution is governed by independent gene
      duplications occurring with identical probability across gene lineages. These
      results suggest that the genome complexity of contemporary vertebrates mostly
      reflect small-scale (regional) DNA duplications instead of large-scale (genomic)
      duplications.

PMID- 29578782
TI  - The Evolutionary Advantages of Dying Young: Epidemiological Implications of
      Longevity in Metapopulations.
AB  - Here we show that pathogen-mediated selection can influence the evolution of host
      longevity. Greater longevity can impair the fitness of host organisms subject to
      pathogen attack, by reducing the mortality rate of infected hosts and thus
      creating a larger and more persistent reservoir of disease, from which infection
      can spread to the healthy population. Where longer-lived and shorter-lived hosts
      can infect one another (and thus all share the same risk of infection), selection
      will favor longer-lived individuals, to the detriment of the host population as a
      whole. But in metapopulations, selection can favor shorter-lived hosts that are
      otherwise identical to their longer-lived competitors, because the populations in
      which they occur will have lower incidence of disease. Under some conditions,
      shorter-lived hosts can even invade metapopulations of longer-lived hosts,
      displacing them and driving them to extinction. Our results support three general
      propositions. First, an organism's life-history traits, and not just its
      resistance genes, can affect its risk of pathogen attack. Second, pathogen
      mediated selection may therefore influence the evolution of host life-history
      traits that are unrelated to resistance, per se. Third, the magnitude-and even
      the direction-of selection on host longevity can depend on the structure of the
      host population.

PMID- 29578783
TI  - The Biological Significance of Fluctuating Asymmetry and Sexual Selection: A
      Reply to Palmer.

PMID- 29578784
TI  - Investment Strategies of Breeders in Avian Cooperative Breeding Systems.
AB  - An individual's optimal investment in young depends partly on the number of
      individuals caring for the same brood. In cooperative breeders, the investment
      strategy of parents with helpers is variable. When parents maintain the same
      effort regardless of helper number, helper care is additive. When parents fully
      compensate for the care of helpers by decreasing their own effort, total care
      does not increase. A study of long-tailed tits Aegithalos caudatus showed that
      both parental strategies may occur within a species, depending on the number of
      helpers. A comparative analysis of 27 cooperative breeders was conducted to test
      the predictions of a graphical model that care is additive when nestling
      starvation is frequent and parents exhibit compensatory reductions in care when
      starvation is rare. Both predictions were supported. In this interspecific
      comparison, a species' mean group size was not associated with compensatory
      responses by parents. There was some evidence that males and females had
      different investment rules. Males tended to show compensatory reductions in care
      when adult survival rate was low. In contrast, while both sexes showed
      compensation when nestling starvation was infrequent, this association was
      significant only for females.

PMID- 29578786
TI  - Detecting Publication Bias in Meta-analyses: A Case Study of Fluctuating
      Asymmetry and Sexual Selection.

PMID- 29578785
TI  - Multiannual Vole Cycles and Population Regulation during Long Winters: An
      Analysis of Seasonal Density Dependence.
AB  - The small-rodent community in northern Fennoscandia shows regular multiannual
      fluctuations in abundance. We analyze time series of spring and fall abundances
      covering 44 yr from the vole community at Kilpisjarvi, northern Finnish Lapland,
      which is dominated by the gray-sided vole (Clethrionomys rufocanus). Treating
      spring and fall abundances as variables in a bivariate time-series model, we
      study seasonal aspects of population regulation and thereby utilize more of the
      available data than in most previous analyses of rodent fluctuations. The
      analysis demonstrates substantial density dependence of population growth during
      the winter. This includes a strong direct effect of previous fall density and a
      strong 2-yr delayed effect of spring density. Population growth during the summer
      shows evidence of delayed density dependence but is generally weaker than that
      during the winter season. Winter regulation appears to be a crucial element in
      the production of multiannual cycles in this community, and we suggest that long
      and severe winters coupled with delayed density dependence may be a direct cause
      of the vole fluctuations in northern and high-elevation areas.

PMID- 29578787
TI  - Extrinsic Modification of Vertebrate Sex Ratios by Climatic Variation.
AB  - Evidence for the influences of climate on early development, maternal condition,
      and offspring viability in terrestrial vertebrates suggests that climatic change
      has the potential to induce variation in offspring sex ratios in such organisms.
      Using long-term data at individual and population levels, we investigated the
      influence of global climatic variation, as a result of the North Atlantic
      Oscillation (NAO), on offspring sex ratios of red deer in Norway. The state of
      the NAO during the fetal development of hinds influenced the mass of their sons,
      but not daughters, and increasingly warmer and snowy winters led to increasingly
      male-biased offspring sex ratios, independently of changes in the mean age of
      hinds. Moreover, hinds that were themselves born following warm, snowy winters
      were smaller as adults, produced significantly lighter sons, and tended to
      produce more sons than hinds born following cold, dry winters. In light of the
      fact that these observations defy explanation according to previous hypotheses of
      adaptive modification of offspring sex ratios, we present the extrinsic
      modification hypothesis, which suggests that sex ratios may evolve in variable
      environments through natural selection independently of maternal strategies of
      sex allocation.

PMID- 29578788
TI  - Stabilization of Mixed-Mating Systems by Differences in the Magnitude of
      Inbreeding Depression for Male and Female Fitness Components.

PMID- 29578789
TI  - Using Phylogenies to Test Macroevolutionary Hypotheses of Trait Evolution in
      Cranes (Gruinae).

PMID- 29578790
TI  - Interspecific Killing among Mammalian Carnivores.
AB  - Interspecific killing among mammalian carnivores is common in nature and accounts
      for up to 68% of known mortalities in some species. Interactions may be
      symmetrical (both species kill each other) or asymmetrical (one species kills the
      other), and in some interactions adults of one species kill young but not adults
      of the other. There is a positive significant relationship between the body
      masses of solitary killer species and body masses of their victim species, and
      grouping species kill larger victims than solitary species. Interactions and
      consumption of the victim appear more common when food is scarce or disputed. In
      response to killers, victim species may alter their use of space, activity
      patterns, and form groups. Consequences of interspecific killing include
      population reduction or even extinction, and reduction and enhancement of prey
      populations, and may therefore have important implications for conservation and
      management of carnivores and their prey.

PMID- 29578791
TI  - Predicting Plant Migration Rates in a Changing World: The Role of Long-Distance
      Dispersal.
AB  - Models of plant migration based on estimates of biological parameters severely
      underestimate the rate of spread when compared to empirical estimates of plant
      migration rates. This is disturbing, since an ability to predict migration and
      colonization rates is needed for predicting how native species will distribute
      themselves in response to habitat loss and climate change and how rapidly
      invasive species will spread. Part of the problem is the difficulty of formally
      including rare long-distance dispersal events in spread models. In this article,
      we explore the process of making predictions about plant migration rates. In
      particular, we examine the links between data, statistical models, and ecological
      predictions. We fit mixtures of Weibull distributions to several dispersal data
      sets and show that statistical and biological criteria for selecting the most
      appropriate statistical model conflict. Fitting a two-component mixture model to
      the same data increases the spread-rate prediction by an average factor of 4.5.
      Data limit our ability to fit more components. Using simulations, we show that a
      small proportion (0.001) of seeds moving long-distances (1-10 km) can lead to an
      order of magnitude increase in predicted spread rate. The analysis also suggests
      that most existing data sets on dispersal will not resolve the problem; more
      effort needs to be devoted to collecting data on long-distance dispersal.
      Although dispersal had the strongest effect on the predicted spread rate, we
      showed that dispersal interacts strongly with plant life history, disturbance,
      and habitat loss in influencing the predicted rate of spread. The importance of
      these interactions means that an approach that integrates local and long-distance
      dispersal with plant life history, disturbance, and habitat availability is
      essential for predicting migration rates.

PMID- 29578792
TI  - A Minimal Model for Forest Fire Regimes.
AB  - We show in this article how the characteristics of fire recurrence in forests can
      be theoretically derived from simple information concerning forest morphology.
      The task is accomplished by means of a minimal model encapsulating a few
      assumptions on the interactions between overstory and understory species and on
      the mechanisms of fire development and transmission. The main difference with
      other models for fire prediction and simulation is that, here, fire is an
      endogenous variable with purely deterministic dynamics. Nevertheless, the
      analysis shows that fire recurrence can be chaotic for parameter values
      corresponding to Mediterranean forests. By contrast, the model shows that boreal
      forests and savannas have the tendency to experience periodic fires. These
      general results are in agreement with the studies carried out on many different
      forests in this century.

PMID- 29578793
TI  - Demographic Stochasticity and Social Mating System in the Process of Extinction
      of Small Populations: The Case of Passerines Introduced to New Zealand.
AB  - Underlying the many causes of extinction of small populations is the random fate
      of each constituent individual or, in other words, demographic stochasticity.
      Demographic stochasticity is inherent to any demographic process, regardless of
      the environment, and its strength increases as population size gets smaller. In
      particular, random fluctuations in the proportion of males and females and the
      way they pair for reproduction (i.e., the social mating system) are usually
      neglected. To assess the potential importance of demographic stochasticity to the
      extinction process, a two-sex model with an explicit mating system was built.
      Extinction probabilities computed via Monte Carlo simulation were compared to
      real data, the case of passerines introduced to New Zealand a century ago. This
      minimal model of extinction allowed assessment of the importance of the mating
      system in the colonization process. Monogamous mating led to a higher extinction
      risk than did polygynous mating. Demographic uncertainty imposes high extinction
      probabilities on short-lived bird species as compared to long-lived bird species.
      Theoretical results for two-sex models are provided.

PMID- 29578794
TI  - Sex Roles Are Not Always Reversed When the Potential Reproductive Rate Is Higher
      in Females.
AB  - Sex roles were examined in a cardinalfish, Apogon notatus, in which males alone
      mouthbrood the eggs received from a single female. Before spawning, a male and
      female formed a pair, within which the female is more active in courtship and
      attacks against conspecifics. Females had a higher potential for reproduction and
      on average produced more than twice as many clutches as those mouthbrooded by a
      male in a season by changing mates after spawning. Animals in which mating
      competition is more intense among females and, ultimately, sexual selection is
      more strongly acting on females are defined as sex-role reversed. Sex-role
      reversal is expected where the operational sex ratio (OSR) is female biased. In
      A. notatus, however, the OSR was male biased throughout the breeding season. This
      was due primarily to a higher mortality in females. The theory predicts that
      sexual selection operates more strongly on the sex toward which the OSR is
      biased. The facts that the variance in reproductive success was greater in males
      and the males developed a sexual trait suggest that sexual selection is acting
      more strongly on males than on females. Accordingly, this fish is not sex-role
      reversed.

PMID- 29578795
TI  - An Improved Procedure for Testing the Effects of Key Innovations on Rate of
      Speciation.

PMID- 29578796
TI  - El Nino-Southern Oscillation-Driven Rainfall Variability and Delayed Density
      Dependence Cause Rodent Outbreaks in Western South America: Linking Demography
      and Population Dynamics.
AB  - It is well known that some rodent populations display dramatic density
      fluctuations in semiarid regions of western South America after the unusual
      rainfall levels associated with El Nino-southern oscillation (ENSO) disturbances.
      These correlated phenomena have led some ecologists to believe that rodent
      outbreaks are determined solely by density-independent factors (e.g., rainfall
      regime). However, demographic studies have detected strong delayed density
      dependent effects in one of the most irruptive rodent species, the leaf-eared
      mouse Phyllotis darwini. We tested the effects of rainfall and delayed density
      dependent factors by constructing a structured model based on demographic data
      estimated from a capture-mark-recapture study of this species in Chile. A model
      including both rainfall and delayed density-dependent effects predicts the
      observed population dynamics rather accurately over a 10-yr period.
      Interestingly, small changes in model parameters result in large changes in model
      dynamics, which strongly suggests that local variations in demographic features
      are important in explaining the asynchronous pattern in outbreak occurrences.
      These findings suggest that inextricably intertwined endogenous and exogenous
      forces cause rodent outbreaks in western South America. The former are
      characterized by delayed nonlinear feedbacks, whereas the latter are
      characterized by the positive effects of the El Nino phases and the negative
      effects of the La Nina phases of the ENSO disturbance.

PMID- 29578797
TI  - How Do Grazers Achieve Their Distribution? A Continuum of Models from Random
      Diffusion to the Ideal Free Distribution Using Biased Random Walks.
AB  - A conceptual model is described for generating distributions of grazing animals,
      according to their searching behavior, to investigate the mechanisms animals may
      use to achieve their distributions. The model simulates behaviors ranging from
      random diffusion, through taxis and cognitively aided navigation (i.e., using
      memory), to the optimization extreme of the Ideal Free Distribution. These
      behaviors are generated from simulation of biased diffusion that operates at
      multiple scales simultaneously, formalizing ideas of multiple-scale foraging
      behavior. It uses probabilistic bias to represent decisions, allowing multiple
      search goals to be combined (e.g., foraging and social goals) and the
      representation of suboptimal behavior. By allowing bias to arise at multiple
      scales within the environment, each weighted relative to the others, the model
      can represent different scales of simultaneous decision-making and scale
      dependent behavior. The model also allows different constraints to be applied to
      the animal's ability (e.g., applying food-patch accessibility and information
      limits). Simulations show that foraging-decision randomness and spatial scale of
      decision bias have potentially profound effects on both animal intake rate and
      the distribution of resources in the environment. Spatial variograms show that
      foraging strategies can differentially change the spatial pattern of resource
      abundance in the environment to one characteristic of the foraging strategy.

PMID- 29578799
TI  - A Longitudinal Study of the Relation Between Family Functioning and Preschool
      ADHD Symptoms.
AB  - The present study examined the bidirectional relation between family functioning
      and attention-deficit/hyperactivity disorder (ADHD) symptoms across the preschool
      years. Participants included 197 (110 boys) 3-year-old children (M = 44.14
      months, SD = 3.43; 60% White) with and without behavior problems and their
      parents who took part in a 3-year longitudinal study. Parenting, parent
      psychopathology, life stress, and child symptoms were assessed annually from ages
      3 to 6. Cross-lagged models provided evidence for both parent and child effects
      for mothers. In particular, greater maternal overreactive parenting and life
      stress were predictive of more child ADHD symptoms, and greater child ADHD
      symptoms significantly predicted greater maternal life stress and depressive
      symptoms and lower warmth, controlling for child oppositional defiant disorder
      and parent ADHD symtoms. Child effects were evident for fathers' depression and
      life stress, but these did not remain controlling for paternal ADHD symptoms.
      Findings suggest that targeting child ADHD symptoms, maternal overreactive
      parenting, and maternal stress each hold promise for attenuating the negative
      mutual influence of child ADHD symptoms and family functioning over time.

PMID- 29578800
TI  - The Hea/r/tist Part: Turning the Point of Mothering Toward 100.
AB  - In this Defining Moments essay, I story the a/r/tographical practice of coming to
      understand who I am as a mother, artist, researcher, and teacher in the face of
      my experiences with infertility, pregnancy loss, and the death of my son Milo.
      Through living inquiry and artistically capturing the turning points that have
      defined me over time, I make sense of what it means to do hea/r/t work as I
      engage compassionate love alongside those I mother.

PMID- 29578801
TI  - Problems With Reliability of Speech Variables for Use in Quality Registries for
      Cleft Lip and Palate-Experiences From the Swedish Cleft Lip and Palate Registry.
AB  - OBJECTIVE: To test the reliability of the speech data in the Swedish quality
      registry for cleft lip and palate. DESIGN: Retrospective study. SETTING: Primary
      care university hospital. PARTICIPANTS: Ninety-four children born with cleft
      palate with or without cleft lip between 2005 and 2009 who had been assessed and
      registered in the quality registry at the age of 5 years. MAIN OUTCOME MEASURES:
      Data in the registry on percent oral consonants correct, percent oral errors,
      percent nonoral errors, perceived velopharyngeal function (PVPF), and
      intelligibility were compared with results based on reassessments by 3
      independent raters from audio recordings. Agreement was calculated by the
      intraclass correlation coefficient (ICC), quadratic weighted kappa, and
      percentage agreement. RESULTS: Absolute agreement calculated by average measures
      ICC for percent oral consonants correct, percent oral errors, and percent nonoral
      errors was above >0.90. Single measures ICC for percent oral consonants correct
      was 0.82, for percent oral errors 0.69, and for percent nonoral errors 0.83. The
      kappa coefficient for PVPF was 0.5 to 0.59 and for intelligibility 0.65 to 0.77.
      Exact percentage agreement for PVPF was 33% and for intelligibility 47.8%.
      CONCLUSIONS: The data on oral consonants correct and nonoral errors in the
      quality registry seem to be reliable. The data on oral errors, PVPF, and
      intelligibility should be interpreted with caution. If differences among
      treatment centers are detected, one should go back and examine the collected raw
      data before drawing any definitive conclusions about treatment outcome.

PMID- 29578802
TI  - Comparative Analysis of Three-Dimensional Nasal Shape of Casts from Patients With
      Unilateral Cleft Lip and Palate Treated at Two Institutions Following Rotation
      Advancement Only (Iowa) or Nasoalveolar Molding and Rotation Advancement in
      Conjunction With Primary Rhinoplasty (New York).
AB  - OBJECTIVES: To compare 3-dimensional nasal symmetry in patients with UCLP who had
      either rotation advancement alone or nasoalveolar molding (NAM) followed by
      rotation advancement in conjunction with primary nasal repair. DESIGN: Pilot
      retrospective cohort study. MATERIALS AND METHODS: Nasal casts of 23 patients
      with UCLP from 2 institutions were analyzed; 12 in the rotation advancement only
      group (Iowa) and 11 in the NAM, rotation advancement with primary nasal repair
      group (New York). Casts from patients aged 6 to 18 years were scanned using the
      3Shape scanner and 3-dimensional analysis of nasal symmetry performed using 3dMD
      Vultus software, Version 2507, 3dMD, Atlanta, GA. Cleft and noncleft side
      columellar height, nasal dome height, alar base width, and nasal projection were
      linearly measured. Inter- and intragroup analyses were performed using t tests
      and paired t tests as appropriate. RESULTS: A statistically significant
      difference in mean-scaled 3-dimensional asymmetry index was found between groups
      with group 1 having a larger measure of asymmetry (4.69 cm3) than group 2 (2.56
      cm3; P = .02). Intergroup analysis performed on the most sensitive linear
      measure, alar base width, revealed significantly less asymmetry on average in
      group 2 than in group 1 ( P = .013). CONCLUSION: This study suggests the NAM
      followed by rotation advancement in conjunction with primary nasal repair
      approach may result in less nasal asymmetry compared to rotation advancement
      alone.

PMID- 29578803
TI  - Opioid Sparing in Cleft Palate Surgery.
AB  - OBJECTIVE: This study aimed to determine whether intraoperative acetaminophen was
      able to decrease opioid consumption, pain scores, and length of stay while
      increasing oral intake in cleft palate surgery. DESIGN/SETTING/PATIENTS: One
      hundred consecutive patients with cleft palate who underwent a von Langenbeck or
      2-flap palatoplasty and intravelar veloplasty at a tertiary medical center by the
      2 senior authors from 2010 to 2015 were reviewed. INTERVENTIONS: Three
      intraoperative treatment groups were analyzed: intravenous (IV) acetaminophen,
      per rectal (PR) acetaminophen, and no acetaminophen. All patients received long
      acting local anesthesia infiltration before incision. Additionally, all patients
      were admitted overnight and given weight-based per oral (PO) acetaminophen and
      oxycodone and IV morphine as needed based on pain scores. OUTCOMES MEASURED: The
      study outcomes included pain scores, opioid requirement, length of stay, and oral
      intake. RESULTS: The treatment groups were comprised of 40 patients who received
      IV acetaminophen, 22 PR acetaminophen, and 35 none. Concerning demographic data,
      there was no statistical difference between treatment groups. There was no
      statistically significant difference for opioid intake, although both IV and PR
      acetaminophen groups had decreased pain scores ( P = .029). There was no
      difference in oral intake ( P = .13) or length of stay ( P = .31) between
      treatment groups. CONCLUSION: In this study, intraoperative administration of
      acetaminophen was associated with decreased pain scores, but no opioid-sparing
      effect. As other studies have shown an opioid-sparing effect with postoperative
      acetaminophen, we recommend withholding the intraoperative dose and beginning
      therapy in the immediate postoperative period.

PMID- 29578804
TI  - Modifications in Presurgical Nasoalveolar Molding Treatment of Bilateral Cleft
      Lip and Palate Patients With Severely Malpositioned Premaxillae.
AB  - OBJECTIVE: The aim of this study was to evaluate a modified presurgical
      nasoalveolar molding (PNAM) treatment for patients with bilateral cleft lip and
      palate (BCLP) with severely malpositioned premaxillae. SETTING: This study was
      conducted at the Faculty of Dentistry, Department of Orthodontics, Ege
      University, Bornova, Izmir, Turkey. METHOD: Retention arms were manufactured
      using a mold that we developed, and prefabricated retraction apparatuses were
      applied to the plaster model obtained from the patient. During the acrylic curing
      process, the flanges of the appliances were elongated into the sulcus without
      including the premaxilla. The premaxilla was aligned with the midline with an
      elastic band system, and the lip hanger was constructed with 0.023-in stainless
      steel wire. Elastic bands were stretched between the retraction apparatuses and
      the lip hanger based on the desired force. Nasal stents were added to the
      retention arms when the cleft width was reduced to less than 6 mm. CONCLUSION:
      The modified PNAM treatment enabled faster derotation of the premaxilla and
      earlier initiation of retraction. The prefabricated retraction apparatus and
      retention arm provided efficient PNAM for patients with BCLP.

PMID- 29578805
TI  - Diagnosis and Innovative Multidisciplinary Management of Hallermann-Streiff
      Syndrome: 20-Year Follow-Up of a Patient.
AB  - Hallermann-Streiff syndrome (HSS) is a rare congenital disorder that mainly
      affects head and face development. We described the different patterns of the
      disease throughout the whole growth period and provided innovative treatment
      steps. Indeed, early genioplasty and dental implantation before growth completion
      were performed. These steps allowed to improve facial growth and to provide
      orthodontic anchorage, respectively. Complementary orthognathic surgery achieved
      satisfactory occlusion and refined aesthetics. We believe such an approach could
      be considered as a relevant treatment modality to complete multidisciplinary care
      in patients with HSS.

PMID- 29578806
TI  - Improved Early Cleft Lip and Palate Complications at a Surgery Specialty Center
      in the Developing World.
AB  - OBJECTIVE: To evaluate complication rates following cleft lip and cleft palate
      repairs during the transition from mission-based care to center-based care in a
      developing region. PATIENTS AND DESIGN: We performed a retrospective review of
      3419 patients who underwent cleft lip repair and 1728 patients who underwent
      cleft palate repair in Guwahati, India between December 2010 and February 2014.
      Of those who underwent cleft lip repair, 654 were treated during a surgical
      mission and 2765 were treated at a permanent center. Of those who underwent cleft
      palate repair, 236 were treated during a surgical mission and 1491 were treated
      at a permanent center. SETTING: Two large surgical missions to Guwahati, India,
      and the Guwahati Comprehensive Cleft Care Center (GCCCC) in Assam, India. MAIN
      OUTCOME MEASURE: Overall complication rates following cleft lip and cleft palate
      repair. RESULTS: Overall complication rates following cleft lip repair were 13.2%
      for the first mission, 6.7% for the second mission, and 4.0% at GCCCC. Overall
      complication rates following cleft palate repair were 28.0% for the first
      mission, 30.0% for the second mission, and 15.8% at GCCCC. Complication rates
      following cleft palate repair by the subset of surgeons permanently based at
      GCCCC (7.2%) were lower than visiting surgeons ( P < .05). CONCLUSIONS: Our
      findings support the notion that transitioning from a mission-based model to a
      permanent facility-based model of cleft care delivery in the developing world can
      lead to decreased complication rates.

PMID- 29578807
TI  - Comparison of the Basal View and a Previously Standardized Cleft Lip Rating
      Scale.
AB  - OBJECTIVES: Numerous scales assessing the aesthetics of cleft lip repair exist.
      Most, including the Asher-McDade scale, use frontal and lateral views, while
      neglecting a basal view. We believe this view is important for properly assessing
      the aesthetics of repair. In this study, we evaluate the basal view in comparison
      to the Asher-McDade scale. METHODS: This scale was based on progressive
      columellar shortening and alar flaring/slumping. A panel of 4 plastic surgeons
      applied the basal and Asher-McDade scales to pictures of patients with repaired
      unilateral cleft lip in 56 multiethnic participants aged 5 years to 18 years;
      images were scored from 1 to 5 (best). Statistical analysis was done via Spearman
      correlation. RESULTS: Scores from plastic surgeons correlated strongly for each
      view. There was moderate correlation for the basal view with both nasal form and
      deviation scores ( P < .05). As expected, there were no strong correlations
      between the basal view and vermillion border or profile. DISCUSSION: The Asher
      McDade scale has been used to evaluate cleft lift repairs but is limited due to
      its subjective nature. The basal view scale grades these repairs by using a scale
      of progressive columellar shortening and alar flaring/slumping, which provides an
      opportunity for quantification and standardization. Our results show that the
      basal view correlates with the Asher-McDade scale among raters, thus providing an
      objective and validated measure of cleft lip repair.

PMID- 29578808
TI  - Characteristics of dementia patients who described or did not describe the
      relationship between two people on the COGNISTAT speech sample.
AB  - Speech sample of Cognitive Status Examination (COGNISTAT) is a task in which
      examinees freely talk about what is happening in a presented picture. We
      investigated whether there are differences in the characteristics between
      patients who described or did not describe the relationship between two people in
      the speech sample based on age, gender, cognitive dysfunction, and type of
      dementia (Alzheimer's disease and dementia with Lewy bodies). The participants
      were 60-year-old or older patients diagnosed with Alzheimer's disease or dementia
      with Lewy bodies who undertook the Mini-Mental State Examination (MMSE) and
      COGNISTAT at a general hospital specialized in care for the elderly. MMSE and
      COGNISTAT were performed by a female clinical psychologist in all patients. In a
      stepwise logistic regression analysis using the two groups (description and no
      description groups) as a response variable, and the age, gender, diagnosis, MMSE
      score, and score of each COGNISTAT subtest as explanatory variables, the MMSE
      score (OR = 1.09; 95% CI [1.03, 1.15]) and gender (OR = 1.79; 95% CI [1.09,
      2.93]) factors were extracted. These results indicated that patients with severer
      overall cognitive dysfunction and male patients were unlikely to describe the
      relationship between two people in a speech sample.

PMID- 29578809
TI  - Feasibility and Acceptability of the Gerontological Personality Disorders Scale
      (GPS) in General Practice: A Mixed Methods Study.
AB  - Although the Gerontological Personality Disorders Scale (GPS) can aid in
      detecting personality disorders (PDs) in older adults in general practice, its
      availability does not guarantee its use. This study therefore aimed to examine
      the feasibility and acceptability of the GPS from an older adult, informant, and
      professional perspective. A convergent parallel mixed methods study was
      conducted. Qualitative data were collected through semistructured interviews with
      four general practitioners and four nurse practitioners and were analyzed
      thematically. Quantitative data were collected through a 5-item questionnaire
      completed by 329 older adults and 329 informants. The thematic analysis revealed
      five major themes regarding feasibility and acceptability according to the
      professionals: taboo to ask intimate questions, quite unfamiliar with these
      disorders, assets, PDs are a topic of interest in general practice, and
      preconditions. Descriptive statistics showed that most older adults and
      informants found the GPS items to be clearly phrased, easy to understand, and
      nonconfrontational or not unpleasant to answer. The GPS is a feasible and
      acceptable instrument for detecting PDs in older adults in general practice.
      Educating professionals about PDs in older adults and the GPS is important prior
      to its use in daily practice and might further increase its acceptability.

PMID- 29578810
TI  - Understanding Attachment Transitions Through the Lived Experiences of Young Black
      Gay and Bisexual Men.
AB  - We conducted a mixed-methods study to identify factors that influence transitions
      in attachment style between childhood and adulthood among 28 young Black gay and
      bisexual men (YBGBM) in the United States. We used a phenomenological approach to
      data integration, with the major component to the results being garnered from the
      qualitative interviews. We organized our results by four attachment transition
      groups: stable secure (secure attachment in childhood and young adulthood),
      stable insecure (insecure attachment in childhood and young adulthood), secure to
      insecure (secure in childhood and insecure in adulthood) and insecure to secure
      (insecure in childhood and secure in adulthood). Within each of the typologies,
      two major themes emerged: social support and religion. Generally, transitions
      from secure to insecure attachment were related to experiences of perceived
      rejection by a parental figure during adolescence that corresponded with sexual
      orientation disclosure. Transitions from insecure to secure attachment appeared
      to be related to the absence of an attachment figure early in life, but with the
      acquisition of an attachment figure during early to late adolescence. The
      findings from our study suggest a need for attachment-based approaches to social
      support interventions, as well as for an increased understanding of social and
      cultural factors that impact attachment changes among practitioners who use
      attachment-based therapy models for YBGBM.

PMID- 29578811
TI  - The Validity of the Canadian Occupational Performance Measure (COPM) When Used in
      a Sub-Acute Rehabilitation Setting with Older Adults.
AB  - This study investigated the validity of the Canadian Occupational Performance
      Measure (COPM) when included as one of the scales used by therapists with older
      adults on an inpatient sub-acute rehabilitation setting. Quantitative data from
      36 participants in a sub-acute rehabilitation setting was obtained via the COPM,
      the Functional Independence Measure (FIM) and the Short Form 36 Health Survey (SF
      36) using a pre-post methodology. Pearson's r correlations and linear regression
      analyses were computed. The COPM Performance admission score was significantly
      correlated with the FIM Total and FIM Physical admission scores (p <.05) while
      the COPM Satisfaction admission score was significantly correlated with the FIM
      Total and FIM Physical admission scores (p <.05). The COPM Performance discharge
      score was significantly associated with the FIM Total, FIM Physical, and SF-36
      Physical Health discharge scores (p <.01) while the COPM Satisfaction discharge
      scores was significantly associated with the FIM Total, FIM Physical, and SF-36
      Physical Health discharge scores (p <.01) respectively. Linear regression
      analyses determined that the COPM's Performance admission score uniquely
      explained 8.4% of the SF-36 Physical Health discharge score's total variance (p
      <.05). The results contribute to the COPM's evidence base, supporting its
      convergent validity and predictive validity.

PMID- 29578812
TI  - Palestinian Nurses' and Doctors' Perceptions and Practices Regarding the
      Prevention of Injuries to Children in the Home: An Explorative Qualitative Study.
AB  - Unintentional injuries are a growing global public health problem that causes
      mortality, morbidity, and disability among children. These injuries are common
      among under-fives and form a significant burden on healthcare systems,
      particularly in low- and middle-income countries. Nurses and doctors have a major
      role to play in the prevention of home injuries, as expressed in many
      international reports. In Palestine, there is a paucity of research in this area.
      Therefore, this study aims to explore nurses' and doctors' perceptions and
      practices regarding the prevention of home injuries among children aged under
      five years. A qualitative approach was followed, whereby semi-structured
      interviews were undertaken with 24 nurses and doctors who worked with children in
      a primary health care setting. The derived data were analyzed using thematic
      analysis. This study found that most of the nurses and doctors who were
      interviewed reported positive attitudes toward working on this topic; the
      majority of them attempted to work on injury prevention. Nevertheless, they
      needed further support to fulfil this potential role, as they faced many barriers
      in their daily practice in this area. Policy makers could potentially take
      advantage of this attitude and support them by providing training, resources, and
      time for them to implement this role.

PMID- 29578813
TI  - Comment: conservative management of massive choroidal relapse in retinoblastoma
      patients?

PMID- 29578814
TI  - Mechanisms of Phytonutrient Modulation of Cyclooxygenase-2 (COX-2) and
      Inflammation Related to Cancer.
AB  - The link between chronic inflammation and cancer involves cytokines and mediators
      of inflammatory pathways. Cyclooxygenase-2 (COX-2), a key enzyme in fatty acid
      metabolism, is upregulated during both inflammation and cancer. COX-2 is induced
      by pro-inflammatory cytokines at the site of inflammation and enhanced COX-2
      induced synthesis of prostaglandins stimulates cancer cell proliferation,
      promotes angiogenesis, inhibits apoptosis, and increases metastatic potential. As
      a result, COX-2 inhibitors are a subject of intense research interest toward
      potential clinical applications. Epidemiological studies highlight the potential
      benefits of diets rich in phytonutrients for cancer prevention. Plants contain
      numerous phytonutrient secondary metabolites shown to modulate COX-2. Studies
      have shown that these metabolites, some of which are used in traditional
      medicine, can reduce inflammation and carcinogenesis. This review describes the
      molecular mechanisms by which phytonutrients modulate inflammation, including
      studies of carotenoids, phenolic compounds, and fatty acids targeting various
      inflammation-related molecules and pathways associated with cancer. Examples of
      pathways include those of COX-2, mitogen-activated protein kinase kinase kinase,
      mitogen-activated protein kinase, pro-inflammatory cytokines, and transcription
      factors like nuclear factor kappa B. Such phytonutrient modulation of COX-2 and
      inflammation continue to be explored for applications in the prevention and
      treatment of cancer.

PMID- 29578815
TI  - Response to Khetan and Maitray's "Comment: Conservative management of massive
      choroidal relapse in retinoblastoma patients?"

PMID- 29578816
TI  - The Effect of Evidence-Based Nutrition Clinical Care Pathways on Nutrition
      Outcomes in Adult Patients Receiving Non-Surgical Cancer Treatment: A Systematic
      Review.
AB  - Nutritional decline associated with non-surgical cancer treatment has been well
      documented. The implementation of an evidence-based nutrition care pathway is one
      approach suggested to improve the nutrition outcomes of this group of patients.
      We aimed to systematically review published original research to determine
      whether evidence-based nutrition clinical care pathways, as compared with usual
      care, improve outcomes for patients receiving non-surgical cancer treatment. The
      review was registered with PROSPERO (CRD42017048816) and followed PRISMA
      guidelines. The search strategy was conducted in four databases, and supplemented
      by an internet search, from inception to October 2016. Study quality was assessed
      using the Quality Criteria Checklist for Primary Research. Results were
      synthesized descriptively. Six reports of five studies formed the final library
      with a range of interventions and control practices investigated across several
      diagnostic groups. Nutrition outcomes were reported using multiple approaches
      with either no effect, or in favor of the clinical pathway intervention. Risk of
      bias was low in two studies with some risk in the remaining three studies. It was
      not possible to determine whether the effect on nutritional outcomes was
      attributable to care pathway implementation. The need to extend the evidence base
      through high-quality clinical trials was evident.

PMID- 29578817
TI  - A Dyadic Approach to Pornography Use and Relationship Satisfaction Among
      Heterosexual Couples: The Role of Pornography Acceptance and Anxious Attachment.
AB  - The majority of research on pornography use within committed relationships has
      found such use to be associated with negative outcomes. However, given the
      variability in pornography use among couples, the current study sought to examine
      moderators in the association between pornography use and relationship
      satisfaction in a large sample of heterosexual matched-paired couples (N =
      6,626). Actor-partner interdependence models (APIMs) revealed that for men who
      are more anxiously attached, more pornography use is associated with higher
      relationship satisfaction; whereas for women who are more anxiously attached,
      more pornography use is associated with lower relationship satisfaction. For men
      who are more accepting of pornography, more pornography use is associated with
      more relationship satisfaction; however, for men who are less accepting of
      pornography, more pornography use is associated with less relationship
      satisfaction. There was little difference in relationship satisfaction at
      differing levels of pornography use for women who are high in pornography
      acceptance. For women who are low in pornography acceptance, pornography use is
      associated with less relationship satisfaction. Results are discussed and
      recommendations for practitioners are made through the lens of symbolic
      interaction theory.

PMID- 29578818
TI  - Barriers and Strategies to Engaging Our Community-Based Preceptors.
AB  - ISSUE: This article, from the "To the Point" series that is prepared by the
      Association of Professors of Gynecology and Obstetrics Undergraduate Medical
      Education Committee, is a review of commonly cited barriers to recruiting and
      retaining community-based preceptors in undergraduate medical education and
      potential strategies to overcome them. EVIDENCE: Community-based preceptors have
      traditionally served as volunteer, nonsalaried faculty, with academic
      institutions relying on intrinsic teaching rewards to sustain this model.
      However, increasing numbers of learners, the burdens of incorporating the
      electronic medical record in practice, and increasing demands for clinical
      productivity are making recruitment and retention of community-based preceptors
      more challenging. IMPLICATIONS: General challenges to engaging preceptors, as
      well as those unique to women's health, are discussed. Potential solutions are
      reviewed, including alternative recruitment strategies, faculty development to
      emphasize efficient teaching practices in the ambulatory setting, offers of
      online educational resources, and opportunities to incorporate students in value
      added roles. Through examples cited in this review, clerkship directors and
      medical school administrators should have a solid foundation to actively engage
      their community-based preceptors.

PMID- 29578819
TI  - Effortful Control and Interpersonal Behavior in Daily Life.
AB  - The Cognitive-Affective Processing System (CAPS) was used to examine effortful
      control (EC) as a moderator of daily interpersonal behavior. Participants (N =
      240) were nonclinical young adults who completed a 7-day event-contingent
      experience sampling study of interpersonal perception and affect. Multilevel
      linear models indicated that EC moderated within-person covariation of
      interpersonal warmth and affect activation; high EC individuals reported greater
      momentary warm behaviors when perceiving others as affectively activated. EC also
      amplified between-person covariation of interpersonal warmth between self and
      others; high EC individuals generally responded to perceptions of another's
      warmth with a greater degree of warm behavior. Varying levels of EC predict
      responses to interpersonal perceptions and affect in daily life, suggesting an
      important dimension for interpersonal functioning.

PMID- 29578820
TI  - Effect of applying consistent pressure to the stationary and the moving arm on
      measurement reliability of glenohumeral internal rotation range of motion.
AB  - OBJECTIVES: The aim of this study was to determine the inter-rater reliability of
      glenohumeral internal rotation (GIR) range of motion (ROM) and pressure
      measurements among four measurement methods: (1) Manual stabilization of the
      humeral head and coracoid process (MSHC) without applying consistent pressure
      (ACP) to both the stationary and the moving arms (BSaMA); (2) MSHC with ACP to
      the moving arm; (3) MSHC with ACP to the stationary arm; and (4) MSHC with ACP to
      BSaMA. DESIGN: Test-retest analyses. PARTICIPANTS: 39 subjects with GIR deficit.
      MAIN OUTCOME MEASURES: GIR ROM and pressure were measured on the stationary or
      moving arm by four examiners using the Clinometer application and a pressure
      biofeedback unit. RESULTS: GIR ROM measurement with MSHC and ACP to the moving
      arm resulted in the lowest intra-class correlation coefficient (ICC = .43); the
      ICC for MSHC without ACP to BSaMA was .54; that for MSHC with ACP to the
      stationary arm was .77; and that for MSHC with ACP to BSaMA was highest, at .81.
      CONCLUSION: MSHC with ACP to both arms leads to reliable GIR ROM measurement in a
      clinical setting.

PMID- 29578821
TI  - Personal Income and Substance Use among Emerging Adults in the United States.
AB  - BACKGROUND: Taxation and other policy measures have been implemented across the
      United States to curb the accessibility of substance use, especially among youth.
      While the inverse relationship between price and youth consumption is well known,
      available research on youth earned income and substance use is sparser,
      particularly among emerging adults. OBJECTIVES: We examined the association
      between emerging adult past-year personal income and 30-day substance use.
      METHODS: We analyzed data from Wave 5 (n = 2,202) of the NEXT Generation Health
      Study, an annual survey study administered to a nationally representative sample
      of emerging adults in the U.S. Wave 5 (mean age = 20.28 years, SE = 0.02 years)
      was administered during the 2013-2014 academic year. After grouping participants
      into five levels of self-reported, pre-tax personal income, we used binomial
      logistic regression to examine the association between personal income and
      cigarette smoking, marijuana use, alcohol use, and heavy episodic drinking (HED).
      RESULTS: In unadjusted models, those at certain levels of higher past-year income
      were more likely to smoke cigarettes, consume alcohol, or engage in HED at least
      once in the past 30 days. Several associations remained significant after
      controlling for covariates. Most associations were no longer significant after
      including perceived peer norms as additional covariates. Personal income was not
      associated with 30-day marijuana use in unadjusted or adjusted models.
      Conclusions/Importance: Higher earned income may provide emerging adults greater
      economic access to cigarettes and alcohol, but the association might be partly
      attenuated by social factors, particularly perceived peer norms.

PMID- 29578822
TI  - Pharmacotherapy for chronic non-specific low back pain: current and future
      options.
AB  - INTRODUCTION: Low back pain is associated with a large burden-of-illness. It is
      responsible for the most years lived with disability as compared with any other
      medical condition. A comprehensive overview of the evidence on pharmacological
      treatment options for chronic low back pain is lacking. This review evaluates the
      evidence for the benefits and risks of currently available pharmacological
      treatments for chronic low back pain. Areas covered: The authors focus on the
      recent (Cochrane) systematic reviews and meta-analyses of randomized clinical
      trials covering paracetamol (acetaminophen), NSAIDs, muscle relaxants,
      antidepressants, anticonvulsants, opioids, and other (new) drugs. Expert opinion:
      The overall impression of the efficacy of pharmacological treatments for patients
      with chronic low back pain is rather sobering. The effects on pain reduction and
      improvement of function are commonly small to moderate and short lasting when
      compared to placebo. At the same time, the various types of drugs are not without
      side-effects. This holds especially true for serious side-effects associated with
      (prolonged) use of strong opioids. Future studies on patients with chronic back
      pain should aim to identify subgroups of patients with good response to specific
      pharmacological treatment to facilitate personalized care.

PMID- 29578823
TI  - Possible Allergenic Role of Tropomyosin in Patients with Adverse Reactions after
      Fish Intake.
AB  - In a recent case report, patient's anti-fish tropomyosin IgE was associated with
      gastrointestinal symptoms. We aimed to demonstrate on a wider scale that the
      panallergen tropomyosin should not be limited to invertebrate species and that
      clinically relevant reactions could be elicited by vertebrate tropomyosin. On the
      whole, 19 patients with adverse reactions after fish intake and showing negative
      skin tests with commercial fish extracts were included. Fish tropomyosin was
      recognized by 10/19 patients' IgE by immunoblotting. All patients with
      gastrointestinal complaints after fish intake (6/6) showed an IgE band matching
      with tropomyosin. Cod, albacore, and swordfish tropomyosins were recognized by
      most patients although 3/10 patients did not claim adverse reactions to these
      fish species. Immunoblotting with a battery of antigens from different fish
      species have a high yield of positivity at a band matching with tropomyosin
      molecular weight, even if they have not been claimed to be causative agents of
      symptoms. Tropomyosin is therefore a good candidate to be investigated as a
      clinically relevant fish allergen in patients who report adverse reactions after
      fish intake.

PMID- 29578824
TI  - Probing Water Mobility in Human Dentine with Neutron Spectroscopy.
AB  - The aim of this study was to investigate hydrogen mobility within innate and
      demineralized human dentine. Dentine sections from extracted human molars,
      demineralized or not, were analyzed by combining neutron spectroscopy with
      thermal analysis. For the thermal analysis of the samples, differential scanning
      calorimetry and thermal gravimetric analysis, coupled with Fourier transform
      infrared spectroscopy, were performed. The hydrogen dynamics of water, collagen,
      and hydroxyl groups present in the samples were investigated via neutron
      spectroscopy. From the mass loss observed from the thermogravimetric analysis
      curves up to 600  degrees C, the same amount of organic content is identified in
      the samples. From the differential scanning calorimetry curves, a higher change
      in enthalpy associated with the denaturation of collagen is registered in the
      demineralized dentine; that is, a structural change occurs in the collagen
      subsequent to demineralization. Since the intensity measured by neutron
      spectroscopy is dominated by the signal from hydrogen, in our samples-coming
      mostly from the bulk-like and loosely bound water as well as from the collagen
      itself-higher proton mobility within the demineralized dentine was detected when
      compared with innate dentine. In the demineralized dentine, this proton mobility
      amounts to 80%, while the remaining hydrogen accounts for a combination of 1)
      structural hydroxyls, as a result of the incomplete dissolution of the mineral
      phase by acid etching, and 2) hydrogen tightly bound in the collagen structure.
      By combining neutron spectroscopy with the calorimetry data, our findings support
      the idea that hydroxyapatite protects the collagen in innate dentine.
      Demineralized dentine, however, acts as a sponge where free bulk-like water is
      trapped.

PMID- 29578825
TI  - Reduction of Tribocorrosion Products When Using the Platform-Switching Concept.
AB  - The reduced marginal bone loss observed when using the platform-switching concept
      may be the result of reduced amounts of tribocorrosion products released to the
      peri-implant tissues. Therefore, the purpose of this study was to compare the
      tribocorrosion product release from various platform-matched and platform
      switched implant-abutment couplings under cyclic loading. Forty-eight titanium
      implants were coupled with pure titanium, gold alloy, cobalt-chrome alloy, and
      zirconia abutments forming either platform-switched or platform-matched groups (
      n = 6). The specimens were subjected to cyclic occlusal forces in a wet acidic
      environment for 24 h followed by static aqueous immersion for 6 d. The amount of
      metal ions released was measured using inductively coupled plasma mass
      spectrometry. Microscopic evaluations were performed pre- and postimmersion under
      scanning electron microscope (SEM) equipped with energy-dispersive spectroscopy X
      ray for corrosion assessment at the interface and wear particle characterization.
      All platform-switched groups showed less metal ion release compared with their
      platform-matched counterparts within each abutment material group ( P < 0.001).
      Implants connected to platform-matched cobalt-chrome abutments demonstrated the
      highest total mean metal ion release (218 ppb), while the least total mean ion
      release (11 ppb) was observed in the implants connected to platform-switched
      titanium abutments ( P <= 0.001). Titanium was released from all test groups,
      with its highest mean release (108 ppb) observed in the implants connected to
      platform-matched gold abutments ( P < 0.001). SEM images showed surface
      tribocorrosion features such as pitting and bands of fretting scars. Wear
      particles were mostly titanium, ranging from submicron to 48 um in length. The
      platform-matched groups demonstrated a higher amount of metal ion release and
      more surface damage. These findings highlight the positive effect of the platform
      switching concept in the reduction of tribocorrosion products released from
      dental implants, which consequently may minimize the adverse tissue reactions
      that lead to peri-implant bone loss.

PMID- 29578826
TI  - The Impact of Tobacco Consumption on Rural Household Expenditure and Self-rated
      Health Among Rural Household Members in China.
AB  - OBJECTIVES: To estimate how tobacco consumption affects household expenditure on
      other goods and services in rural China and to assess the tobacco consumption
      affects self-rated health among rural household members in China. METHODS: A
      Seemingly Unrelated Regression was used to assess the impact of tobacco
      consumption on rural household expenditure. To detect tobacco consumption causing
      heterogeneity in self-rated health among adults in rural China, this study
      employed a random effects generalized ordered probit model. 2010-2014 China
      Family Panel Studies was used for the analysis. The data set included 3,611
      households and 10,610 adults in each wave. RESULTS: Tobacco consumption
      households assign significantly lower budget shares to food, health care, dress,
      and education in rural China. Moreover, self-rated health factor has a
      significantly positive coefficient with respect to non-smokers and ex-smokers,
      that is, when the individuals is a non-smoker or ex-smoker, he/ she will be more
      likely to report his/her health status as positive. CONCLUSIONS: The first
      analysis showed that tobacco consumption crowds out expenditures on food, dress,
      health care, and education for rural households in China, and the second analysis
      indicated that non-smokers and ex-smokers are more likely to report their health
      status as better compared with last year. The results of the present study
      revealed that Chinese policymakers might consider controlling tobacco consumption
      since tobacco control can improve not only rural household welfare but also rural
      household members' health status. Therefore, the tobacco tax policy and brief
      clinical interventions by the doctor should be implemented in rural China.

PMID- 29578827
TI  - Burden and Quality of Life of Family Caregivers of Stroke Patients.
AB  - The purpose of this study was to identify the level of burden and quality of life
      of family caregivers of stroke patients and to investigate the correlation
      between burden, quality of life (including physical, social, psychological, and
      environmental domains), age of caregivers, and the care period. A descriptive
      correlational cross-sectional study was performed, with a convenience sample of
      family caregivers (n = 30) of stroke patients in Sao Paulo, Brazil. Data were
      collected using a questionnaire on participants' characteristics, the Zarit
      Burden Interview Scale (ZBIS), and the World Health Organization Quality of Life
      BREF (WHOQOL-BREF) instrument. A descriptive analysis was performed, and
      correlations between variables were analyzed using Pearson's product-moment
      correlation coefficient. The average burden score on the ZBIS was 29.6,
      representing a moderate burden, and the average overall quality of life score on
      the WHOQOL-BREF was 62.06%, which indicates moderate quality of life. A
      significant weak negative correlation was observed between burden and
      environmental domains (r = -0.470; p =.009), quality of life (r = -0.414; p
      =.023), and physical domains (r = -0.394; p =.031). No significant correlations
      were found between burden and quality of life, and variables in the psychological
      and social domains, age of caregivers, or care period. Caregivers for stroke
      patients presented with moderate levels of burden and reduction in quality of
      life. Levels of burden correlated negatively with environmental domains, quality
      of life levels, and physical domains; however, these correlations were weak,
      indicating the possible interference of other factors.

PMID- 29578828
TI  - The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on
      breast cancer cells.
AB  - PURPOSE: The androgen receptor (AR) has attracted attention in the treatment of
      breast cancer. Due to the undesirable side effects of AR agonists, attempts have
      been undertaken to develop selective AR modulators. One of these compounds is Cl
      4AS-1. This study examined this compound more closely at the cellular and
      molecular levels. METHODS: Three different breast cancer cell lines were
      utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453
      cells, and the triple negative, basal MDA-MB-231 cells. RESULTS: High and
      significant concordance between dihydrotestosterone (DHT) and Cl-4AS-1 in
      regulation of gene expression in MDA-MB-453 cells was found. However, some
      differences were noted including the expression of AR, which was upregulated by
      DHT, but not Cl-4AS-1. In addition, both DHT and Cl-4AS-1 caused a similar
      morphological change and reorganization of the actin structure of MDA-MB-453
      cells into a mesenchymal phenotype. Treatment of cells with DHT resulted in
      induction of proliferation of MCF-7 and MDA-MB-453 cells, but no effect was
      observed on the growth of MDA-MB-231 cells. On the other hand, increasing doses
      of Cl-4AS-1 resulted in a dose-dependent inhibition on the growth of the three
      cell lines. This inhibition was a result of induction of apoptosis whereby Cl-4AS
      1 caused a block in entry of cells into the S-phase followed by DNA degradation.
      CONCLUSIONS: These results indicate that although Cl-4AS-1 has characteristics of
      classical AR agonist, it has dissimilar properties that may make it useful in
      treating breast cancer.

PMID- 29578829
TI  - "They Gave Me Life": Motherhood and Recovery in a Tribal Community.
AB  - OBJECTIVE: This study explored factors related to substance misuse and recovery
      among Native mothers in a Pacific Northwest tribe, focusing on motherhood as a
      motivating factor in seeking treatment and sustaining recovery. METHOD: Using a
      community-based participatory research approach, we conducted a thematic analysis
      of 20 in-depth interviews and one focus group (N = 12) with Native women 18 years
      and older living on or near the reservation. RESULTS: Qualitative findings
      highlighted challenges, motivations and strategies for seeking treatment and
      recovery in four major themes: (a) the close relationship between interpersonal
      violence and substance misuse; (b) traditional healing in recovery; (c) community
      specific challenges to recovery; and (d) the motivating role of motherhood in
      seeking treatment and successful recovery. CONCLUSIONS: A central finding of this
      work is that pregnancy and motherhood may be underexplored factors in Native
      women's substance use. Results support previous work suggesting that Native women
      are at high risk of interpersonal trauma and that trauma contributes to substance
      misuse. Findings offer several rich implications for treatment and recovery among
      Native mothers in tribal communities including the necessity of trauma-informed
      treatment, community and culturally-based interventions, more integration of
      treatment services with Child Protective Services, and drawing on motherhood as a
      motivation for seeking and succeeding in recovery.

PMID- 29578830
TI  - Mortality and Cause of Death-A 30-Year Follow-Up of Substance Misusers in Sweden.
AB  - BACKGROUND: This article presents a 30-year follow-up study of a cohort of 1163
      substance misusers who were in inpatient treatment in the early 1980s. Data was
      originally collected in the Swedish Drug Addict Treatment Evaluation (SWEDATE).
      OBJECTIVES: The aim is to examine the overall mortality and identify causes of
      death in different groups based on self-reported most dominant substance misuse
      among those who have died during January 1984-December 2013. METHODS: SWEDATE
      data was linked to the National Cause of Death Register. Five mutually exclusive
      study groups were created based on self-reported most dominant substance misuse
      for the last 12 months before intake to treatment: Alcohol, Cannabis, Stimulants,
      Opiates, and Other. The Standardized Mortality Ratio (SMR) was calculated.
      RESULTS: During the follow-up, 40% died. SMR is 10.3 for women and 11.7 for men.
      The study groups differed regarding SMR; 13.1 in the Alcohol group, 9.2 in the
      Cannabis group, 9.6 in the Stimulants group, 16.7 in the Opiates group and 10.8
      in the Other group. Drug related death was the most common cause of death (28%
      only underlying, 19% both underlying and contributing) followed by alcohol
      related reasons (17% vs. 9%). CONCLUSIONS: Alcohol misuse among substance abusers
      might have a negative impact on mortality rates. Methodological changes in how
      drug related deaths is registered affects the interpretation of the statistics of
      cause of death. Further analysis on the relation between drug related cause of
      death and drug misuse related death is needed.

PMID- 29578831
TI  - Is It Feasible and Safe to Wake Cardiac Arrest Patients Receiving Mild
      Therapeutic Hypothermia After 12 Hours to Enable Early Neuro-Prognostication? The
      Therapeutic Hypothermia and Early Waking Trial Protocol.
AB  - Mild therapeutic hypothermia (MTH 33 degrees C) post out-of-hospital cardiac
      arrest (OHCA) is widely accepted as standard of care. However, uncertainty
      remains around the dose and therapy duration. OHCA patients are usually kept
      sedated+/-paralyzed and ventilated for the first 24-36 hours, which allows for
      targeted temperature management, but makes neurological prognostication
      challenging. The aim of this study is to investigate the feasibility and safety
      of assessing the unconscious OHCA patient after 12 hours for early
      waking/extubation while continuing to provide MTH for 24 hours, and fever
      prevention for 72 hours by using an intravenous temperature management (IVTM)
      system and established conscious MTH anti-shiver regimens. This is a single
      center, prospective, non-randomized observational study that will compare the
      results of early awakening (at 12 hours) with historical controls. A total of 50
      consecutive unconscious survivors of OHCA, treated with MTH, who meet the
      Therapeutic Hypothermia and eArly Waking (THAW) inclusion criteria will be
      enrolled. The patient will receive MTH by using IVTM. After 12 hours of MTH,
      patients will be assessed by using strict clinical criteria to determine
      suitability for early waking and extubation. Once awake and extubated, MTH will
      continue for 24 hours with skin counter-warming and anti-shiver regimen followed
      fever prevention up to 72 hours. All patients will have serial
      electroencephalogram (EEG), somatic sensory potential, and neuro-biomarkers
      performed on admission to intensive care unit, 6 and 12 hours, then every 24
      hours until 72 hours. The study has been approved by the National Research Ethics
      Service, Health Research Authority.

PMID- 29578832
TI  - Pilot Randomized Trial of an Automated Smoking Cessation Intervention via Mobile
      Phone Text Messages as an Adjunct to Varenicline in Primary Care.
AB  - OBJECTIVE: Varenicline is a safe and effective aid to smoking cessation but most
      trials have involved frequent visits or intensive behavioral support unlike that
      typically provided in primary care. The current study examined if motivational
      text messages, sent via cellphone, would increase quit rates in smokers being
      treated with varenicline and 3 brief sessions in a family practice setting.
      METHODS: This study was a randomized controlled, parallel-group smoking cessation
      trial. Intervention group participants (n = 74) received daily motivational text
      messages, additional texted tips in response to keywords, and weekly study
      questions while control group participants (n = 76) received only weekly study
      questions. Both groups received individualized counseling. Self-reported non
      smoking and exhaled breath CO <10ppm were used to validate smoking abstinence at
      3 weeks and 12 weeks. RESULTS: Overall, 30.7% (46/150) of participants were
      abstinent at the 12 week follow-up and the abstinence rate did not differ between
      groups (INT 31.1% v. CON 30.3%, p = .91). The only predictor of abstinence at 12
      weeks was use of varenicline during a previous quit attempt (p = .01).
      Intervention group participants were more likely to rate the text messaging
      program as good or excellent (p < .01), to recommend a similar program to family
      or friends (p < .01), and to complete positive smoking cessation activities (p =
      .04), when compared with the control group. CONCLUSION: Although there were no
      differences in quit rates between the intervention and control group,
      intervention group participants rated the text messaging system more favorably,
      were more likely to recommend the program to others, and were more likely to
      complete positive smoking cessation activities.

PMID- 29578833
TI  - Program theory within policy-initiated evaluations: the Norwegian low-income
      family study.
AB  - Using as an example a project where the Norwegian Labor and Welfare Directorate
      developed a comprehensive model for the follow-up of low-income families, this
      article demonstrates the process of developing a program theory for policy
      initiated interventions. The data consist of interviews with program developers,
      political documents from early stages, and observations of the program's
      development. The results demonstrate that, although research inspired the program
      developers, the program was also the outcome of policy priorities, experiences
      from earlier projects, and input from the practice field. Multiple sources
      contributed to its relevance for the practice field, however, increasing its
      complexity. The program includes several intervention levels and follow-up areas
      and partially builds on elements found to be important across interventions.
      Although a program theory can be difficult to conceptualize within policy
      initiated interventions, it is important to articulate it prior to evaluation
      and, if necessary, reassess it when data have been analyzed.

PMID- 29578834
TI  - Adverse drug events and medication problems in "Hospital at Home" patients.
AB  - "Hospital at Home(HaH)" programs provide an alternative to traditional
      hospitalization. However, the incidence of adverse drug events in these programs
      is unknown. This study describes adverse drug events and potential adverse drug
      events in a new HaH program. We examined the charts of the first 50 patients
      admitted. We found 45 potential adverse drug events and 14 adverse drug events
      from admission to 30 days after HaH discharge. None of the adverse drug events
      were severe. Some events, like problems with medication administration, may be
      unique to the hospital at home setting. Monitoring for adverse drug events is
      feasible and important for hospital at home programs.

PMID- 29578835
TI  - The Center for Social Innovation at Boston College.
AB  - Established in 2011, the Center for Social Innovation at Boston College has
      focused on fostering "effective, sustainable social innovations that enhance
      social justice." the Center is committed to building research evidence that is
      used for changing practice and works to disseminate findings through a three
      channel approach: traditional research publications, convening of practitioners,
      and through use of media outlets.

PMID- 29578837
TI  - My Entrance, Her Exit.

PMID- 29578836
TI  - Protective effects of photobiomodulation against resistance exercise-induced
      muscle damage and inflammation in rats.
AB  - We investigated whether low-level laser therapy (LLLT) prior to or post
      resistance exercise could attenuate muscle damage and inflammation. Female Wistar
      rats were assigned to non-LLLT or LLLT groups. An 830-nm DMC Laser Photon III was
      used to irradiate their hind legs with 2J, 4J, and 8J doses. Irradiations were
      performed prior to or post (4J) resistance exercise bouts. Resistance exercise
      consisted of four maximum load climbs. The load work during a resistance exercise
      bout was similar between Control (non-LLLT, 225 +/- 10 g), 2J (215 +/- 8 g), 4J
      (210 +/- 9 g), and 8J (226 +/- 9 g) groups. Prior LLLT did not induce climbing
      performance improvement, but exposure to 4J irradiation resulted in lower blood
      lactate levels post-exercise. The 4J dose decreased creatine kinase and lactic
      dehydrogenase levels post-exercise regardless of the time of application.
      Moreover, 4-J irradiation exposure significantly attenuated tumor necrosis factor
      alpha, interleukin-6, interleukin-1beta, cytokine-induced neutrophil
      chemoattractant-1, and monocyte chemoattractant protein-1. There was minor
      macrophage muscle infiltration in 4J-exposed rats. These data indicate that LLLT
      prior to or post resistance exercise can reduce muscle damage and inflammation,
      resulting in muscle recovery improvement. We attempted to determine an ideal LLLT
      dose for suitable results, wherein 4J irradiation exposure showed a significant
      protective role.

PMID- 29578838
TI  - Reliability and Validity of Finger Strength and Endurance Measurements in Rock
      Climbing.
AB  - PURPOSE: An advanced system for the assessment of climbing-specific performance
      was developed and used to: (a) investigate the effect of arm fixation (AF) on
      construct validity evidence and reliability of climbing-specific finger-strength
      measurement; (b) assess reliability of finger-strength and endurance
      measurements; and (c) evaluate the relationship between finger flexor all-out
      test scores and climbing ability. METHODS: To determine the effect of AF, 22 male
      climbers performed 2 maximal strength and all-out tests with AF (shoulder and
      elbow flexed at 90 degrees ) and without AF (shoulder flexed at 180 degrees  and
      elbow fully extended). To determine reliability, 9 male climbers completed 2
      maximal strength tests with and without AF and an all-out and intermittent test
      without AF. RESULTS: The maximal strength test without AF more strongly
      determined climbing ability than the test with AF (r2 = .48 and r2 = .42 for
      sport climbing; r2 = .66 and r2 = .42 for bouldering, respectively). Force and
      time variables were highly reliable; the rate of force development and fatigue
      index had moderate and low reliability. The maximal strength test with AF
      provided slightly higher reliability than without AF (intraclass correlation
      coefficient [ICC] = 0.94, ICC = 0.88, respectively). However, smaller maximal
      forces were achieved during AF (484 +/- 112 N) than without AF (546 +/- 132 N).
      All-out test average force had sufficiently high reliability (ICC = 0.92) and a
      relationship to sport climbing (r2 = .42) and bouldering ability (r2 = .58).
      CONCLUSION: Finger strength and endurance measurements provided sufficient
      construct validity evidence and high reliability for time and force parameters.
      Arm fixation provides more reliable results; however, the position without AF is
      recommended as it is more related to climbing ability.

PMID- 29578839
TI  - Utilizing risk index for overdose or serious opioid-induced respiratory
      depression (RIOSORD) scores to prioritize offer of rescue naloxone in an
      outpatient veteran population: A telephone-based project.
AB  - BACKGROUND: Since 2014, the Department of Veterans Affairs (VA) has been working
      to address the ongoing opioid epidemic through opioid-education initiatives, the
      development of risk calculators, and other risk stratification tools. One primary
      focus of VA efforts has been the distribution of rescue naloxone kits to veterans
      at greatest risk of opioid-related adverse events. The purpose of this project
      was to identify primary care veterans at highest risk for serious opioid-related
      adverse events using the Risk Index for Overdose and Serious Opioid-Induced
      Respiratory Depression (RIOSORD) and offer rescue naloxone kits by telephone
      based outreach. RIOSORD is a risk-stratification tool developed and validated
      within the veteran population. METHODS: Veterans identified at highest risk of
      overdose or opioid-related adverse effects were contacted by telephone or letter
      to offer to provide a rescue naloxone kit between November 1st, 2016 and February
      1st, 2017. The primary outcome of the project was the percentage of patients
      contacted that agreed to a naloxone prescription. Secondary outcomes included
      comparative efficacy of phone versus letter contact and reasons for refusal of
      naloxone if the offer was declined. RESULTS: Of 41 veterans targeted by this
      project, most were successfully reached by telephone within three attempts
      (92.7%, n = 38). Approximately two-thirds of those reached by telephone agreed to
      a prescription for rescue naloxone (n = 26, 63.4%). The veterans that requested
      rescue naloxone selected the nasal formulation (n = 17) over the intramuscular
      auto-injector (n = 9). CONCLUSIONS: This project demonstrated that telephone
      based outreach can be one method of distributing rescue naloxone to a high-risk
      patient population without requiring an in-person visit to a provider.

PMID- 29578840
TI  - Emotional arousal deficit or emotional regulation bias? An electrophysiological
      study of age-related differences in emotion perception.
AB  - : Background/Study context: Adult age differences in emotion processing have been
      attributed to age-related decline in earlier emotional perception and age-related
      bias in later emotional regulation. Yet, the relationship between the processes
      of early emotion perception and bias in emotional regulation and their influence
      on behavioral outcomes remains unclear. Event-related potentials (ERPs) have the
      temporal precision to allow for the online measure of neurophysiological activity
      and provide potential insight into the complex dynamics of emotion processing and
      aging. METHODS: ERPs were used as the primary measure to examine the hypotheses
      that younger adults will differ in emotional arousal and emotional bias as
      represented by the early P1 waveform and later P3 waveform, respectively. Thirty
      two younger and older adults (16 each) performed a facial emotion discrimination
      task in which they identified standardized angry, happy, or neutral expressions
      of faces from the NimStim database. RESULTS: Younger adults showed a greater P1
      ERP for angry faces relative to happy faces at parietal channels, while older
      adults did not exhibit any emotional modulation of the P1. In contrast, both
      younger and older adults showed a greater late P3 ERP for angry faces compared to
      happy faces. CONCLUSION: The authors' results provide evidence for an age-related
      deficit in early emotion perception and autonomic arousal. Younger adults, but
      not older adults, exhibited a pattern of neurophysiological activity believed to
      reflect preconscious and reflexive identification of threat. Despite these age
      group differences in early emotion processing, younger and older adults did not
      exhibit differences in neurophysiological processes believed to reflect emotion
      regulation.

PMID- 29578841
TI  - Achieving body confidence for young children: Development and pilot study of a
      universal teacher-led body image and weight stigma program for early primary
      school children.
AB  - Negative body image attitudes develop in early childhood and there is a need for
      school-based resources during the early school years, but no teacher-delivered
      curriculum-based resources exist to mitigate these attitudes in young children.
      Achieving Body Confidence for Young Children (ABC-4-YC), a universal body
      dissatisfaction and weight stigma prevention program, was developed and then
      delivered in a pilot study. Fifty-one 5- to 8-year-old children completed pre-
      and post-intervention interviews assessing body image attitudes, and seven
      teachers provided feedback. Significant improvement in body esteem and positive
      teacher feedback were found. The results provide preliminary support for ABC-4-YC
      to improve children's body image attitudes, but extensive evaluation is needed.

PMID- 29578842
TI  - Associations of Perceived Discrimination With Impaired Functioning in a
      Population Sample With Psychological Distress.
AB  - OBJECTIVE: To test associations between perceived discrimination based on mental
      health status and impaired functioning in a population sample with psychological
      distress. METHODS: Interviews were conducted with a sample of respondents to the
      California Health Interview Survey with mild, moderate, or severe psychological
      distress. Perceived discrimination was assessed using 14 items covering four
      domains in which discrimination is reported: social, partner, institutional, and
      work. Associations of perceived discrimination scores (total score and domain
      scores) with impaired functioning, measured by the likelihood and number of days
      out of role, were estimated with statistical adjustment for demographic
      characteristics and serious psychological distress. RESULTS: Discrimination
      domain scores are significantly correlated (r ranging from .34 to .65).Total
      discrimination score is associated with having days out of role (OR = 1.20, 95%
      CI = 1.10-1.30) and with number of days out of role (5.5 days) after adjustment
      for demographics and psychological distress. The high correlation among the
      domain scores makes the attribution of association to particular domains
      uncertain. Removal of the effect of discrimination using model-based simulation
      reduces past-year days out of role by 39.4 (SE 11.3) days. CONCLUSIONS: This
      observational study supports the suggestion that discrimination against people
      with mental illness contributes to their impaired functioning in a diverse range
      of social roles. The results provide preliminary evidence that reduction in
      discrimination against people with mental illness could improve social
      functioning and work productivity. Correlations among domain scores make it
      difficult to draw conclusions about domain-specific associations.

PMID- 29578843
TI  - Psychosocial Services for Individuals With Serious Mental Illness/Severe
      Emotional Disturbance: Clinical Practice Guideline Toolkit.
AB  - This article presents a short, easy-to-use guideline for clinicians working with
      people with serious mental illness, particularly those with schizophrenia,
      schizoaffective disorder, delusional disorders, other psychotic disorders, or
      depression with significant impact on functioning, and may be of use for those
      working with individuals with bipolar disorder. This guideline is not meant to
      supplant the more detailed, excellent clinical practice guidelines that have been
      developed and published. Rather, the charts and explanation presented here are
      designed as a step-by-step tool that clinicians can use to ensure they are
      following the most appropriate course of action and providing the best
      psychosocial rehabilitation services possible for persons with these disorders.
      Program managers can use this tool to evaluate the processes used in their system
      to ensure that appropriate services are offered for the individuals in their
      care. This guideline is also not meant as a substitute for comprehensive training
      in the practice of assessment and treatment for individuals with serious mental
      illness. Very little detail is provided about the disorders, appropriate
      assessments, and interventions because clinicians providing services to people
      with these disorders should have received the specialized training necessary to
      appropriately deliver the services needed by these individuals.

PMID- 29578845
TI  - Negative stereotypes as motivated justifications for moral exclusion.
AB  - We investigated the connection between moral exclusion of outgroups and on the
      one hand, right-wing authoritarianism (RWA), and social dominance orientation
      (SDO) on the other. We assumed that both RWA and SDO would increase the tendency
      to place other groups out of the scope of justice. However, we also tested
      whether negative stereotypes about an outgroup's threatening and norm-violating
      misbehavior would serve as a justification for moral exclusion. These assumptions
      were tested in connection with Roma, Jewish, and Muslim people as target groups
      in the Hungarian context (N = 441). In line with our hypotheses, we found that
      both RWA and SDO had an indirect effect on moral exclusion mediated by negative
      stereotypes about the particular target group. Our findings suggested that
      negative stereotypes were more important legitimizing factors for RWA than for
      SDO. Our results highlight the benefits of interpreting the process of moral
      exclusion as an outcome of motivated social cognition.

PMID- 29578844
TI  - Home health nurse decision-making regarding visit intensity planning for newly
      admitted patients: a qualitative descriptive study.
AB  - Despite patients referred to home health having diverse and complex needs, it is
      unknown how nurses develop personalized visit plans. In this qualitative
      descriptive study, we interviewed 26 nurses from three agencies about their
      decision-making process to determine visit intensity and analyzed data using
      directed content analysis. Following a multifactorial assessment of the patient,
      nurses relied on their experience and their agency's protocols to develop the
      personalized visit plan. They revised the plan based on changes in the patient's
      clinical condition, engagement, and caregiver availability. Findings suggest
      strategies to improve visit planning and positively influence outcomes of home
      health patients.

PMID- 29578846
TI  - Understanding complex care for older adults within Canadian home care: a
      systematic literature review.
AB  - In the context of an aging population, both the need for home care services and
      its complexity of care have increased in many high-income countries. Yet, the
      definition of what constitutes complex care is largely elusive. This systematic
      review examined the conceptual definition of complex care within the home care
      environment using several social and health science databases for research
      published from 2000 to 2017. Of the 25 articles and reports identified, only 16
      addressed complex care specifically and included older adults, aging, and/or home
      care. The results showed that complex care for older adults is primarily defined
      from a biomedical approach focusing on chronic disease and management and less
      commonly from the perspective of the social determinants of health. Future
      studies should consider the importance of the continuum of care needs from both
      the biomedical and the social determinants to adequately plan and provide care
      for older adults.

PMID- 29578847
TI  - Development of Quality Indicators to Assess Oral Anticoagulant Management in
      Community Pharmacies for Patients with Atrial Fibrillation.
AB  - BACKGROUND: Few studies have evaluated the quality of oral anticoagulant
      management by community pharmacists. There is no complete set of quality
      indicators available for this purpose. OBJECTIVE: To develop a set of specific
      quality indicators to assess oral anticoagulant management by community
      pharmacists for patients with atrial fibrillation (AF). METHODS: Quality
      indicators were developed in 3 phases. In phase 1, potential quality indicators
      were generated based on clinical guidelines and a literature review. In phase 2,
      a modified RAND appropriateness method involving 2 rounds was implemented with 9
      experts, who judged the appropriateness of quality indicators generated in phase
      1 based on the extent to which they were accurate, based on evidence, relevant,
      representative of best practices, and measurable in community pharmacies. Phase 3
      consisted of a feasibility assessment in 5 community pharmacies on 2 patients
      each. RESULTS: The final set included 38 quality indicators grouped into 6
      categories: documentation (n = 29), risk assessment (n = 3), clinical control (n
      = 1), clinical follow-up (n = 15), choice of therapy (n = 11), and interaction
      management (n = 8). The quality indicators referred to process of care (n = 34),
      clinical outcomes (n = 2), or structure of care (n = 2). There were 24 quality
      indicators related to vitamin K antagonists (VKAs), and 17 were related to direct
      oral anticoagulants (DOACs). To assess quality indicators, a questionnaire was
      developed for completion by community pharmacists for each patient, which
      included 17 questions about VKA patients and 12 questions about DOAC patients.
      CONCLUSIONS: A first set of quality indicators is now available to assess the
      quality of oral anticoagulant management by community pharmacists for patients
      with AF. DISCLOSURES: This research was supported by the Reseau Quebecois de
      recherche sur le medicament (RQRM); the Blueprint for Pharmacy in collaboration
      with Pfizer Canada; and the Cercle du Doyen of the Faculty of Pharmacy,
      University of Montreal. The study sponsors were not involved in the study design,
      data collection, data interpretation, the writing of the article, or the decision
      to submit the report for publication. Chartrand received a scholarship from the
      Fonds de Recherche du Quebec en Sante (FRQ-S), the Reseau Quebecois de recherche
      sur l'usage des medicaments with Pfizer, and the Faculty of Pharmacy, University
      of Montreal. Guenette holds a Junior-1 Clinician Researcher Award from the FRQ-S
      in partnership with the Societe quebecoise d'hypertension arterielle. Williamson
      holds a Junior-1 Career Award from the FRQ-S. Cote reported being a medical
      speaker for Bayer, Boehringer Ingelheim Canada, and Pfizer Canada. The other
      authors reported no conflicts of interest. Study concept and design were
      contributed by Lalonde, Chartrand, and Martin. Chartrand, Martin, and Lalonde
      collected the data, along with Brouillette, Cote, Huot, Landry, Martineau,
      Perreault, Williamson, and White-Guay. Data interpretation was performed by
      Chartrand, Gagnon, and Lalonde, along with Guenette and Martin. The manuscript
      was primarily written by Chartrand, along with Guenette and Lalonde, and revised
      by Chartrand, Guenette, and Lalonde, along with the other authors. A portion of
      this study's results was presented at the 4th RQRM Annual Meeting on September 22
      23, 2014, in Orford, Quebec, Canada, in the form of an abstract, which was
      published in the Journal of Population Therapeutics and Clinical Pharmacology,
      2014;21(2):e312.

PMID- 29578848
TI  - The Additional Costs per Month of Progression-Free Survival and Overall Survival:
      An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib
      for Second-Line Treatment of Metastatic Renal Cell Carcinoma.
AB  - BACKGROUND: When considering optimal second-line treatments for metastatic renal
      cell carcinoma (mRCC), clinicians and payers seek to understand the relative
      clinical benefits and costs of treatment. OBJECTIVE: To use an economic model to
      compare the additional cost per month of overall survival (OS) and of progression
      free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for
      the second-line treatment of mRCC from a third-party U.S. payer perspective.
      METHODS: The model evaluated mean OS and PFS and costs associated with drug
      acquisition/administration; adverse event (AE) treatment; monitoring; and
      postprogression (third-line treatment, monitoring, and end-of-life costs) over 1-
      and 2-year horizons. Efficacy, safety, and treatment duration inputs were
      estimated from regimens' pivotal clinical trials; for everolimus, results were
      weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated
      using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and
      administration inputs were consistent with approved prescribing information and
      the clinical trials used to estimate efficacy and safety inputs. Cost inputs came
      from published literature and public data. Additional cost per additional month
      of OS or PFS was calculated using the ratio of the cost difference per treated
      patient and the corresponding difference in mean OS or PFS between everolimus and
      each comparator. One-way sensitivity analyses were conducted by varying efficacy
      and cost inputs. RESULTS: Compared with everolimus, cabozantinib, nivolumab, and
      axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS,
      respectively, over 1 year. Cabozantinib and nivolumab were associated with
      additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2
      years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer
      months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of
      treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1 year
      were $34,141, $19,371, and $17,506 higher, respectively. Everolimus had similar
      OS and lower costs compared with axitinib. The additional cost per month of OS
      was $48,773 for cabozantinib and $24,214 for nivolumab versus everolimus. The
      additional treatment cost with cabozantinib, nivolumab, or axitinib versus
      everolimus for each additional month of PFS was estimated at $21,338, $64,570,
      and $35,012, respectively. Over 2 years, the additional costs per additional
      month of OS for nivolumab and axitinib versus everolimus were similar to the 1
      year analysis; for cabozantinib, the cost was lower. Results were sensitive to
      changes in mean OS, mean PFS, therapy duration, and drug costs estimates.
      CONCLUSIONS: Everolimus for second-line mRCC was associated with similar OS and
      lower costs compared with axitinib over 1- and 2-year horizons. The additional
      cost per additional month of OS and PFS associated with cabozantinib or nivolumab
      versus everolimus creates a metric for evaluating the cost of second-line
      therapies in relation to their respective treatment effects. DISCLOSURES: Funding
      for this research was provided by Novartis, which was involved in all stages of
      study research and manuscript preparation. Ghate and Perez are employees of
      Novartis and own stock/stock options. Swallow, Messali, McDonald, and Duchesneau
      are employees of Analysis Group, which has received consultancy fees from
      Novartis. Study concept and design were contributed by Swallow, Messali, Ghate,
      and Perez, along with McDonald and Duchesneau. Swallow, Messali, McDonald, and
      Duchesneau collected the data, and all authors participated in data
      interpretation. The manuscript was written by Swallow, Messali, and Ghate, along
      with the other authors, and revised by Swallow, Messali, Ghate, and Perez. A
      synopsis of the current research was presented in poster format at the 15th
      International Kidney Cancer Symposium on November 4-5, 2016, in Miami, Florida.

PMID- 29578849
TI  - Disparities in Initial Oral Antidiabetic Medication Adherence Among Veterans with
      Incident Diabetes.
AB  - BACKGROUND: Medication nonadherence is a prevalent public health issue,
      particularly among patients with diabetes mellitus (DM), and negatively affects
      health outcomes. Because of the prevalence of DM among U.S. veterans, it is
      crucial to understand how well these patients adhere to oral antidiabetic (OAD)
      medication and whether certain subgroups are more likely to be nonadherent.
      OBJECTIVE: To assess initial OAD medication use among veterans with uncomplicated
      DM and determine factors associated with adherence in the first 2 years of
      treatment. METHODS: This was a retrospective cohort study using data from the
      Veterans Affairs (VA) Corporate Data Warehouse from 2002 through 2014. The first
      diagnosis for uncomplicated DM was determined, and then medication use was
      assessed following OAD initiation. OAD use was assessed by proportion of days
      covered (PDC) for the first 2 years of therapy using outpatient VA pharmacy
      records. Adherence was determined both continuously and categorically, with a PDC
      of >= 80% used to indicate adherence. Logistic regression was used to determine
      if certain patient characteristics were associated with being adherent to OADs.
      RESULTS: A total of 148,544 veterans with uncomplicated DM were assessed, most of
      whom were white, aged >= 55 years, and initiated OAD therapy on metformin. A
      large portion resided in the southern part of the United States. In the first
      year, PDC averaged 79.2% (SD = 25.9), and 63.2% were adherent to OAD therapy;
      however, these numbers declined in the second year, when the average PDC was
      71.3% (SD = 35.8), and only 59.1% were adherent. Over the course of both years,
      PDC averaged 75.3% (SD = 28.4), and 50.9% were adherent. The odds of being
      adherent were higher among older adults and significantly lower among veterans
      self-identifying as either African American (OR = 0.61; 95% CI = 0.59-0.63),
      Native American (OR = 0.67; 95% CI = 0.61-0.75), or Hawaiian/Pacific Islander (OR
      = 0.84; 95% CI = 0.76-0.92) when compared with whites. Veterans who were either
      divorced/separated (OR = 0.86; 95% CI = 0.83-0.88) or never married (OR = 0.89;
      95% CI = 0.86-0.93) also had lower odds of being initially adherent to OAD
      therapy compared with those who reported being married. Being nonadherent in year
      1 was highly predictive of remaining nonadherent in year 2 (OR = 12.8; 95% CI =
      12.23-12.94), with only 22.2% nonadherent in the first year (8.2% overall)
      becoming adherent in the second year of therapy. Across both years, all
      minorities were less likely to be adherent (compared with whites), and average
      adherence differed among all geographic regions of the country. CONCLUSIONS:
      Within the first year of OAD therapy, medication adherence was suboptimal among
      veterans with DM, and second-year results indicate that adherence is likely to
      decline over time. Future studies should consider deeper regional and subgroup
      analysis to determine what contributes to variation in medication use in
      communities across the country. DISCLOSURES: This study was supported by a KL2
      Career Development Grant from the University of Tennessee Health Science Center's
      Institute for Research, Innovation, Synergy and Health Equity and by resources
      from the U.S. Department of Veterans Affairs. Hung and Kovesdy are employees of
      the Department of Veterans Affairs. Opinions expressed are those of the study
      authors and do not necessarily reflect the views of the Department of Veterans
      Affairs. None of the authors declared significant relevant financial conflicts of
      interest. Results of this study were presented as a poster at the Academy of
      Managed Care Pharmacy Nexus Conference on October 3-6, 2016, in National Harbor,
      Maryland.

PMID- 29578850
TI  - Assessing Quality of Care in Pharmacy: Remembering Donabedian.
AB  - : While some incremental and fragmented progress has been made in recent years,
      assessing the quality of care provided by pharmacists and pharmacy organizations
      remains an elusive goal. Revisiting the simple, elegant model of quality
      assessment originally proposed by physician and scholar Avedis Donabedian can
      assist pharmacy quality managers to develop a more comprehensive approach to
      measuring, monitoring, and managing the quality of care. DISCLOSURES: No funding
      supported the writing of this article. The author has no relevant conflicts of
      interest to disclose.

PMID- 29578851
TI  - Refill-Based Medication Use Quality Measures in Kidney Transplant Recipients:
      Examination of Proportion of Days Covered and Medication Possession Ratio.
AB  - BACKGROUND: The Pharmacy Quality Alliance's definition of proportion of days
      covered (PDC) and medication possession ratio (MPR) have not been examined as
      potential quality measures in the kidney transplant recipient population.
      OBJECTIVES: To (a) describe the frequency distribution of MPR and PDC using
      mycophenolic acid products in a real-world kidney transplant recipient population
      and (b) evaluate associations between MPR and PDC with late (> 90 days after
      transplantation) biopsy-proven acute rejection (BPAR). METHODS: This was a
      retrospective cohort study combining data from the Wisconsin Allograft Recipient
      Database with University of Wisconsin (UW) Health Specialty Pharmacy prescription
      claims and dispensing data from March 10, 2006, to June 30, 2012. Patients who
      met criteria for persistence filling mycophenolic acid prescriptions at UW Health
      Specialty Pharmacy in the first year following discharge from kidney
      transplantation surgery hospitalization were included. Patients were excluded if
      they were enrolled in a clinical trial, if they had BPAR within 90 days of
      transplantation, or if they did not have panel reactive antibody data available.
      PDC and MPR were calculated over 360 days after discharge, and multivariable
      analyses were performed to determine if there were associations between PDC or
      MPR with late BPAR within 3 years. RESULTS: This study included 388 patients. The
      incidence of 3-year late BPAR was 5.1% (n = 20). Characteristics of patients who
      experienced late BPAR were largely consistent with those who did not experience
      late BPAR, with the exception of number of hospital readmissions, which was
      higher among patients who experienced late BPAR. The frequency distribution of
      PDC and MPR exhibited a skewed left distribution, with a median PDC of 0.972 and
      a median MPR of 1.000. Higher PDC was associated with lower odds of late BPAR (OR
      = 0.041, 95% CI = 0.004-0.417) in multivariable analysis, as was a higher MPR (OR
      = 0.041, 95% CI = 0.004-0.419). CONCLUSIONS: MPR and PDC may be calculated from
      data available to pharmacies and health plans, and each was associated with 3
      year late BPAR among patients who did not experience early BPAR. However, the
      construct validity of these medication adherence measures requires further study.
      DISCLOSURES: This study was not funded. The authors report no conflicts of
      interest and no relevant financial interests related to the products or services
      discussed in this article. Study concept and design were contributed by Hofmeyer,
      along with Look and Hager. Hager took the lead in data collection, along with the
      other authors. Data interpretation was performed by Look, along with the other
      authors. The manuscript was primarily written by Hofmeyer, assisted by Look and
      Hager, and revised by all of the authors.

PMID- 29578852
TI  - Economic Burden of Patients with Inadequate Response to Targeted Immunomodulators
      for Rheumatoid Arthritis.
AB  - BACKGROUND: Targeted immunomodulators (TIMs), including biologic disease
      modifying antirheumatic drugs (DMARDs) and JAK/STAT inhibitors, are effective
      therapies for rheumatoid arthritis (RA), but some patients fail to respond or
      lose response over time. This study estimated the real-world prevalence of RA
      patients with inadequate responses to an initial TIM (nonresponders) in the
      United States and assessed their direct and indirect economic burden compared
      with treatment responders. METHODS: Administrative claims data (January 1999
      March 2014) from a large private-insurer database were used, which included work
      loss data from a subset of reporting companies. Eligible patients (classified as
      responders and nonresponders) had >= 1 claim for a TIM approved for the treatment
      of RA and >= 2 RA diagnoses in the claims history, with continuous pharmaceutical
      and medical benefit eligibility for 6 months before (baseline) and 12 months
      after (study period) the date of the first TIM claim (index date). All-cause and
      RA-related health care resource use (HCRU) and costs, work loss, and indirect
      costs during the study period were compared for responders versus nonresponders.
      Multivariable regression was used to adjust for baseline covariates. Sensitivity
      analyses of HCRU and direct costs were conducted for patients with index dates
      before and after 2008 to account for different approval dates of TIMs. RESULTS:
      Of 7,540 eligible patients with RA, 2,527 (34%) were classified as responders,
      and 5,013 (66%) were classified as nonresponders; 407 and 723 had work-loss data,
      respectively. After adjusting for baseline covariates, nonresponders had
      significantly higher HCRU, including inpatient admissions (incidence rate ratio
      [IRR] = 1.94), outpatient visits (IRR = 1.19), emergency department visits (IRR =
      1.53), and number of prescription fills (IRR = 1.09; all, P < 0.001).
      Nonresponders also had significantly higher adjusted all-cause ($12,868 vs.
      $9,621, respectively) and RA-related ($5,740 vs. $4,495; both, P < 0.001) medical
      costs compared with responders. In addition, nonresponders reported significantly
      more days of work lost compared with responders (22.1 vs. 16.7 days,
      respectively; IRR = 1.21; P = 0.007) and higher indirect costs ($3,548 vs.
      $2,890; P = 0.002). Sensitivity analyses of HCRU and direct costs by index date
      (before and after 2008) were consistent with the full sample. CONCLUSIONS: A
      large portion of patients with RA had inadequate responses to their initial TIM
      therapy with significantly higher economic burden, including higher HCRU, medical
      costs, and indirect costs due to work loss, compared with TIM therapy responders.
      DISCLOSURES: Funding for this research was provided by AbbVie, which was involved
      in all stages of the study research and manuscript preparation. Tundia and
      Fuldeore are employed by AbbVie. Song and Macaulay are employed by Analysis
      Group, which received grants from AbbVie to conduct this study. Strand reports
      grants and personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer
      Ingelheim, Celltrion, Corrona, Crescendo, Genentech/Roche, GSK, Janssen, Lilly,
      Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, and UCB outside the
      submitted work. Study concept and design were contributed by Tundia, Song, and
      Macaulay, along with other authors. Data analyses were designed and conducted by
      Song and Macaulay. All authors contributed to data interpretation. Writing of the
      manuscript was led by Tundia, Song, and Macaulay, with revisions by all authors.
      A synopsis of the current research was presented at the American College of
      Rheumatology/Association of Rheumatology Health Professionals meeting, which took
      place in Washington, DC, during November 11-16, 2016.

PMID- 29578853
TI  - Michigan Pharmacists Transforming Care and Quality: Developing a Statewide
      Collaborative of Physician Organizations and Pharmacists to Improve Quality of
      Care and Reduce Costs.
AB  - BACKGROUND: Inappropriate drug use, increasing complexity of drug regimens,
      continued pressure to control costs, and focus on shared accountability for
      clinical measures drive the need to leverage the medication expertise of
      pharmacists in direct patient care. A statewide strategy based on the
      collaboration of pharmacists and physicians regarding patient care was developed
      to improve disease state management and medication-related outcomes. PROGRAM
      DESCRIPTION: Blue Cross Blue Shield of Michigan (BCBSM) partnered with Michigan
      Medicine to develop and implement a statewide provider-payer program called
      Michigan Pharmacists Transforming Care and Quality (MPTCQ), which integrates
      pharmacists within physician practices throughout the state of Michigan. As the
      MPTCQ Coordinating Center, Michigan Medicine established an infrastructure
      integrating clinical pharmacists into direct patient care within patient-centered
      medical home (PCMH) practices and provides direction and guidance for quality and
      process improvement across physician organizations (POs) and their affiliated
      physician practices. The primary goal of MPTCQ is to improve patient care and
      outcomes related to Medicare star ratings and HEDIS measures through integration
      of clinical pharmacists into direct patient care. The short-term goal is to adopt
      and modify Michigan Medicine's integrated pharmacist practice model at
      participating POs, with the long-term goal of developing a sustainable model of
      pharmacist integration at each PO to improve patient care and outcomes.
      Initially, pharmacists are delivering disease management (diabetes, hypertension,
      and hyperlipidemia) and comprehensive medication review services with future
      plans to expand clinical services. OBSERVATIONS: In 2015, 10 POs participated in
      year 1 of the program. In collaboration with the MPTCQ Coordinating Center, each
      PO identified 1 "pharmacist transformation champion" (PTC). The PTC implemented
      the integrated pharmacist model at 2 or 3 practice sites with at least 2
      practicing physicians per site. IMPLICATIONS: MPTCQ is a unique collaboration
      between a large academic institution, physician organizations, a payer, and a
      statewide coordinating center to improve patient care and address medication
      related challenges by integrating pharmacists into a PCMH network. Pharmacists
      can actively provide their medication expertise to physicians and patients and
      optimize quality measure performance. DISCLOSURES: This project was funded by
      Blue Cross Blue Shield of Michigan. Choe and Spahlinger are employees of Michigan
      Medicine. Tungol Lin, Kobernik, Cohen, Qureshi, Leyden, and Darland are employees
      of Blue Cross Blue Shield of Michigan. At the time of manuscript preparation,
      Share and Wesolowicz were employees of Blue Cross Blue Shield of Michigan. Study
      concept and design were primarily contributed by Choe, along with the other
      authors. Choe, Tungol Lin, and Kobernik collected data, and data interpretation
      was performed by Choe, Tungol Lin, Cohen, and Wesolowicz. The manuscript was
      written primarily by Choe, along with Tungol Lin and assisted by Kobernik, Cohen,
      Leyden, and Qureshi. The manuscript was revised by Leyden, Spahlinger, Share, and
      Darland. Material from this manuscript was previously presented as an education
      session at the 2016 AMCP Managed Care & Specialty Pharmacy Annual Meeting; April
      19-22, 2016; San Francisco, California.

PMID- 29578854
TI  - Increasing Access to Hepatitis C Virus Medications: A Program Model Using Patient
      Navigators and Specialty Pharmacy to Obtain Prior Authorization Approval.
AB  - BACKGROUND: Obtaining prior authorization (PA) approval for the new direct-acting
      antiviral (DAA) hepatitis C medications is time consuming and requires specific
      expertise. Our primary care-based program treats hepatitis C virus (HCV)-infected
      patients at an urban academic medical center and employs patient navigators
      trained in the PA process who collaborate with a nurse and specialty pharmacy to
      manage the PA process. OBJECTIVE: To demonstrate the rate of PA approvals for our
      programmatic model and determine potential predictors of PA approval. METHODS: We
      conducted a review of program databases and medical records of patients for whom
      DAA hepatitis C medications were ordered between November 1, 2014, and October
      31, 2015 (n = 197). We first evaluated patient characteristics associated with
      the number of steps to approval. Then we used a multivariable ordinal regression
      to determine independent predictors of fewer steps to approval. Using Kaplan
      Meier methods, we assessed patient characteristics associated with approval time
      and then fit a multivariable Cox regression model to determine independent
      predictors of time to approval. RESULTS: Of the 197 patients, 69% (n = 136) had
      Medicaid; 12% (n = 24) had Medicare; 10% (n = 19) had both Medicaid and Medicare;
      5% (n = 10) had private insurance; and 4% (n = 8) were uninsured. Ninety-three
      percent of the patients were eventually approved for HCV treatment. The steps in
      the PA cascade were approval on first submission (37%; mean days = 30.7; SD =
      29.9); approval after internal appeal (45%; mean days = 66.8; SD = 70.5);
      approval after external appeal (11%; mean days = 124.7; SD = 60.2); and no
      approval obtained (7%). Unadjusted factors found to have a P value < 0.200 in
      relation to fewer steps in the PA cascade were older age, female gender, non
      Medicaid insurance, comorbid hypertension, comorbid diabetes, being domiciled,
      and being nongenotype 2. After adjustment, non-Medicaid insurance and nongenotype
      2 remained significant. In survival analysis, non-Medicaid insurance and mid
      range fibrosis were associated with fewer days to PA approval. CONCLUSIONS: Our
      program obtained 93% of PA approvals for hepatitis C medications. Patient
      navigators collaborating with a nurse and specialty pharmacy as a program may
      improve the PA approval process, although further research with a control group
      is necessary. DISCLOSURES: The Respectful & Equitable Access to Comprehensive
      Healthcare (REACH) program receives funding from the Robin Hood Foundation and
      the New York State Department of Health AIDS Institute. Weiss receives grant
      support from Gilead Sciences and has served as a consultant for AbbVie and Gilead
      Sciences. Vu reports speaker fees from Peer View Institute. All other authors
      report no conflict of interest. Study design and concept were contributed by
      Chasan, Sigel, Vu, and Weiss. Riazi, Ciprian, Giardina, and Gibbs collected the
      data, which were interpreted by Toribio, Amory, Chasan, and Sigel. The manuscript
      was written by Vu and Weiss and revised by Parrella, Cambe, Camacho, and Vu.
      Research from this study was presented as an abstract poster on November 14,
      2016, at the AASLD Liver Meeting in Boston, Massachusetts.

PMID- 29578855
TI  - A Comparison of Pharmacy Dispensing Channel Use and Adherence to Specialty Drugs
      Among Medicare Part D Beneficiaries.
AB  - BACKGROUND: Nonadherence to specialty drugs has been associated with poor
      clinical and economic outcomes. Studies conducted using commercial health plans
      suggest that patients who use specialty pharmacies have higher adherence compared
      with patients using retail pharmacies. However, little is known about the
      frequency of dispensing channel use or the association of dispensing channel use
      with adherence to specialty drugs among Medicare Part D beneficiaries.
      OBJECTIVES: To (a) describe the use of pharmacy dispensing channels by patients
      using self-administered specialty drugs in Medicare Part D and (b) study the
      association between dispensing channel use and adherence to specialty drugs in
      this population. METHODS: This study analyzed 2010 Medicare Part D data.
      Specialty drugs were defined as drugs with a mean cost >= $600 per month. We
      identified the top 13 specialty medications by cost and classified patients into
      the following classes: anticancer, disease-modifying therapy (DMT), and tumor
      necrosis factor inhibitor (TNFi). Dispensing channels included retail, specialty,
      mail order, long-term care, and other. We included patients continuously enrolled
      in Medicare Part D who had >= 1 prescription for a specialty medication before
      the end of June 2010. These patients were followed until the end of 2010.
      Patients with proportion of days covered (PDC) >= 0.8 were considered adherent.
      Adherence rates were calculated by weighting for therapeutic class after
      weighting for drug mix. Multivariable logistic regression analysis examined the
      association between dispensing channel and adherence. RESULTS: Of 5,430 patients,
      1,248 were dispensed anticancer medications, 1,723 were dispensed DMTs, and 2,459
      were dispensed TNFi drugs. About 16% used specialty, 74% used retail, 4% used
      mail order, 4% used long-term care, and 3% used other channels. The distribution
      pattern was similar when stratified by therapeutic class. In the descriptive
      analysis, patients using the specialty channel for the anticancer and TNFi
      classes had 7% and 10% higher adherence rates, respectively, compared with
      retail. For the DMT class, the adherence rate was higher for mail order but
      similar for retail and specialty channels. Adjusted analysis found that overall,
      specialty users had 23% higher odds for being adherent compared with retail users
      (P = 0.0104). For the anticancer and TNFi classes, specialty users had 39% (P =
      0.0311) and 55% (P = 0.0005) higher odds, respectively, for being adherent than
      retail users. For the DMT class, no significant association was observed between
      dispensing channel and adherence (P = 0.9691). CONCLUSIONS: Nearly three quarters
      of Medicare patients on specialty therapies included in this study used the
      retail channel compared with one sixth who used the specialty channel. Overall,
      specialty channel use was associated with higher adherence compared with retail
      channel use. However, this relationship varied by therapeutic class. The
      specialty channel was associated with higher adherence among patients from the
      anticancer and TNFi classes but not among the DMT class. DISCLOSURES: No funding
      supported this study. The authors reported no potential conflicts of interest.
      Kale, Patel, and Carroll were responsible for study concept and design. Data
      analysis was conducted by Kale, assisted by Patel. The manuscript was written
      primarily by Kale, with assistance from Carroll. Some findings from this study
      were presented during the poster presentation at the Academy of Managed Care
      Pharmacy Nexus held in National Harbor, Maryland, on October 4, 2016.

PMID- 29578856
TI  - Drug treatment of hypertension in older patients with diabetes mellitus.
AB  - INTRODUCTION: Hypertension is more prevalent in the elderly (age>65 years)
      diabetic population than in the general population and shows an increasing
      prevalence with advancing age. Both diabetes mellitus (DM) and hypertension are
      independent risk factors for cardiovascular (CV) related morbidity and mortality.
      Optimal BP targets were not identified in elderly patients with DM and
      hypertension. Areas covered: In this review article, the authors briefly discuss
      the pathophysiology of hypertension in elderly diabetics, present evidence with
      various antihypertensive drug classes supporting the treatment of hypertension to
      reduce CV events in older diabetics, and then discuss the optimal target BP goals
      in these patients. Expert opinion: Clinicians should have a BP goal of less than
      130/80 mm in all elderly patients with hypertension and DM, especially in those
      with high CV-risk. When medications are required for optimal BP control in
      addition to lifestyle measures, either thiazide diuretics, angiotensin-converting
      enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers
      should be considered as initial therapy. Combinations of medications are usually
      required in these patients because BP control is more difficult to achieve in
      diabetics than those without DM.

PMID- 29578857
TI  - Interest in prescribing buprenorphine among resident and attending physicians at
      an urban teaching clinic.
AB  - BACKGROUND: Opioid use disorders are a major medical and public health concern.
      Buprenorphine is approved for the treatment of opioid use disorders; however, a
      shortage of physicians prescribing buprenorphine is a significant barrier to
      treatment access. The aims of this study were to evaluate opinions of internal
      medicine attending and resident physicians about buprenorphine and assess
      interest in becoming waivered to prescribe. METHODS: Internal medicine resident
      and attending physicians at a primary care clinic in a large academic hospital
      were invited to complete surveys. The study sample was composed of physicians who
      were not waivered to prescribe buprenorphine. Survey data included demographic
      information, level of training, buprenorphine waiver status, interest in becoming
      waivered to prescribe buprenorphine, and beliefs about buprenorphine for
      treatment of opioid use disorders. High interest in becoming waivered was defined
      as a Likert response >3 (1 = No interest, 5 = Very interested). RESULTS: Of the
      44 physician respondents, 39 were not waivered to prescribe buprenorphine and
      constituted the sample; of those, 27 were residents and 12 were attending
      physicians. Twenty-six of the 39 nonwaivered respondents (66.7%) had high
      interest in becoming waivered. Those with high interest in becoming waivered were
      significantly more likely to be younger (P = .007) and to strongly believe in
      buprenorphine effectiveness (P = .023). DISCUSSION: Most physicians in this
      academic training program showed high interest in prescribing buprenorphine, and
      belief in buprenorphine effectiveness was associated with high interest in
      becoming waivered.

PMID- 29578859
TI  - Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic
      Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle.
AB  - PURPOSE: To develop and characterize vitamin A (VA)-coupled liposomes for the
      targeted delivery of BMP4-siRNA to hepatic stellate cells (HSC). VA was selected
      to increase the uptake by HSC based on their function in the storage of VA.
      METHODS: DOTAP/DOPE liposomes were prepared by film hydration method and their
      surfaces were decorated with VA. The cytotoxicity of VA-conjugated liposomes was
      evaluated by the WST-1 assay. Inhibition of BMP4 and alpha-SMA was determined by
      PCR and ELISA. RESULTS: VA-coated lipoplexes exhibited an average particle sizes
      less than 200 nm and zeta potential around +25 mV both determined using ZetaPALS.
      Inclusion of VA to liposomal surfaces significantly enhanced their cellular
      uptake without affecting cytotoxicity. VA-coupled liposomes carrying BMP4-siRNA
      resulted in a significant reduction in BMP4 and alpha-SMA at both mRNA and
      protein levels.  Conclusion: VA-coated liposomes were successfully designed to
      deliver BMP4-siRNA to specifically target HSC. The novel delivery system
      discussed herein may serve as a potential therapeutic strategy for the treatment
      of liver fibrosis in the future. This article is open to POST-PUBLICATION REVIEW.
      Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the
      issue's contents page.

PMID- 29578858
TI  - Water-Based Aerobic Training Successfully Improves Lipid Profile of Dyslipidemic
      Women: A Randomized Controlled Trial.
AB  - PURPOSE: This study aimed to investigate the effects of water-based aerobic
      training on the lipid profile and lipoprotein lipase (LPL) levels in
      premenopausal women with dyslipidemia. METHOD: Forty women were randomly assigned
      to: aquatic training (WA; n = 20) or a control group (CG; n = 20). The WA group
      underwent 12 weeks of water-based interval aerobic training twice a week at
      intensities ranging from 9 to 15 on the Borg Scale of Perceived Exertion. Total
      cholesterol (TC), triglycerides (TG), high- (HDL) and low- (LDL) density
      lipoprotein, TC/HDL ratio, LPL levels, and peak oxygen consumption (VO2peak) were
      evaluated before and after 12 weeks in both groups. RESULTS: The WA group
      elicited decreases in TC (9%; effect size [ES] = 0.69; 95% CI [0.05, 1.33]), LDL
      (16%; ES = 0.78; 95% CI [0.13, 1.42]), and the TC/HDL ratio (17%; ES = 1.13; 95%
      CI [0.46, 1.79]), as well as increases in VO2peak (10%; ES = 0.64; 95% CI [0.002,
      1.27]) and HDL (10%; ES = 0.28; 95% CI [-0.35. 0.90]), without significant
      changes in TG (ES = 0.16; 95% CI [-0.46, 1.79]) and LPL (ES = 0.36; 95% CI [
      0.27, 0.98]) levels. In the CG, no statistically significant changes in any of
      these variables were found (TC, ES = 0.19, 95% CI [-0.43, 0.82]; LDL, ES = 0.22,
      95% CI [-0.40, 0.85]; HDL, ES = 0.05, 95% CI [-0.57, 0.67]; TG, ES = 0.09, 95% CI
      [-0.53, 0.71]; TC/HDL ratio, ES = 0.20, 95% CI [-0.42, 0.82]; LPL, ES = 0.02, 95%
      CI [-0.60, 0.64]; VO2peak, ES = 0.20, 95% CI [-0.42, 0.82]). CONCLUSION: Water
      based interval aerobic training positively affected the lipid profile in
      premenopausal dyslipidemic women.

PMID- 29578860
TI  - Positive Bacteriological Analyses in Individuals With Diabetes Mellitus:
      Preliminary Results From a Forensic Study.
AB  - Increased infection susceptibility in the diabetic population is a controversial
      issue in the clinical field. The greater frequency of infections in diabetic
      patients has been speculated as caused by the hyperglycemic environment that
      favors immune dysfunction. The aim of this study was to investigate the
      proportion of positive bacterial cultures in a series of diabetic individuals who
      underwent forensic investigations and assess the frequency of hyperglycemia at
      the time of death in these cases as well as the percentage of diabetics with
      cause of death due to bacterial infection. Forensic autopsy cases characterized
      by positive bacterial cultures and pre-existing diagnosis of diabetes mellitus
      were included in the study. Initial findings revealed that 12% (7/58 cases) of
      positive bacterial cultures concerned individuals with a pre-existing diagnosis
      of diabetes mellitus. Bacterial infection was considered to be the cause of death
      in 22% (7/31 cases) of diabetics with positive bacterial cultures. Hyperglycemia
      could be identified in 1 case only at the time of death. These preliminary
      results highlight the usefulness of systematically performing postmortem
      bacteriology in the forensic setting to more precisely characterize infectious
      risk factors in diabetics.

PMID- 29578862
TI  - Inhalational versus Intravenous Induction of Anesthesia in Children with a High
      Risk of Perioperative Respiratory Adverse Events: A Randomized Controlled Trial:
      Erratum.

PMID- 29578861
TI  - Alzheimer Disease Biomarkers and Driving in Clinically Normal Older Adults: Role
      of Spatial Navigation Abilities.
AB  - PURPOSE: Older adults experience impaired driving performance, and modify their
      driving habits, including limiting amount and spatial extent of travel. Alzheimer
      disease (AD)-related pathology, as well as spatial navigation difficulties, may
      influence driving performance and driving behaviors in clinically normal older
      adults. We examined whether AD biomarkers [cerebrospinal fluid (CSF)
      concentrations of Abeta42, tau, and ptau181] were associated with lower self
      reported spatial navigation abilities, and whether navigation abilities mediated
      the relationship of AD biomarkers with driving performance and extent. METHODS:
      Clinically normal older adults (n=112; aged 65+) completed an on-road driving
      test, the Santa Barbara Sense of Direction scale (self-report measure of spatial
      navigation ability), and the Driving Habits Questionnaire for an estimate of
      driving extent (composite of driving exposure and driving space). All
      participants had a lumbar puncture to obtain CSF. RESULTS: CSF Abeta42, but not
      tau or ptau181, was associated with self-reported navigation ability. Lower self
      reported navigation was associated with reduced driving extent, but not driving
      errors. Self-reported navigation mediated the relationship between CSF Abeta42
      and driving extent. CONCLUSIONS: Findings suggest that cerebral amyloid
      deposition is associated with lower perceived ability to navigate the
      environment, which may lead older adults with AD pathology to limit their driving
      extent.

PMID- 29578863
TI  - Electrical Impedance Tomography for Confirmation of Lung Isolation during One
      lung Ventilation.

PMID- 29578864
TI  - Spinal Protein Kinase Mzeta Regulates alpha-Amino-3-hydroxy-5-methyl-4
      isoxazolepropionic Acid Receptor Trafficking and Dendritic Spine Plasticity via
      Kalirin-7 in the Pathogenesis of Remifentanil-induced Postincisional Hyperalgesia
      in Rats.
AB  - BACKGROUND: Intraoperative remifentanil anesthesia exaggerates postoperative pain
      sensitivity. Recent studies recapitulate the significance of protein kinase Mzeta
      in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor
      mediated pathologic pain. Kalirin-7, a Rho guanine nucleotide exchange factor,
      coordinates AMPA receptor trafficking and dendritic spine plasticity. This study
      examines whether protein kinase Mzeta and Kalirin-7 contribute to remifentanil
      induced postincisional hyperalgesia via AMPA receptor. METHODS: Plantar incision
      was performed 10 min after the start of remifentanil infusion (1 ug . kg . min
      for 60 min). Paw withdrawal threshold (primary outcome), spinal protein kinase
      Mzeta activity, Kalirin-7 expression, AMPA receptor trafficking, and spine
      morphology were assessed. Protein kinase Mzeta inhibitor and Kalirin-7 knockdown
      by short hairpin RNA elucidated the mechanism and prevention of hyperalgesia.
      Whole-cell patch-clamp recording analyzed the role of protein kinase Mzeta in
      spinal AMPA receptor-induced current. RESULTS: Remifentanil reduced
      postincisional paw withdrawal threshold (mean +/- SD, control vs. hyperalgesia,
      18.9 +/- 1.6 vs. 5.3 +/- 1.2 g, n = 7) at postoperative 48 h, which was
      accompanied by an increase in spinal protein kinase Mzeta phosphorylation (97.8
      +/- 25.1 vs. 181.5 +/- 18.3%, n = 4), Kalirin-7 production (101.9 +/- 29.1 vs.
      371.2 +/- 59.1%, n = 4), and number of spines/10 um (2.0 +/- 0.3 vs. 13.0 +/-
      1.6, n = 4). Protein kinase Mzeta inhibitor reduced remifentanil-induced
      hyperalgesia, Kalirin-7 expression, and GluA1 trafficking. Incubation with
      protein kinase Mzeta inhibitor reversed remifentanil-enhanced AMPA receptor
      induced current in dorsal horn neurons. Kalirin-7 deficiency impaired
      remifentanil-caused hyperalgesia, postsynaptic GluA1 insertion, and spine
      plasticity. Selective GluA2-lacking AMPA receptor antagonist prevented
      hyperalgesia in a dose-dependent manner. CONCLUSIONS: Spinal protein kinase Mzeta
      regulation of GluA1-containing AMPA receptor trafficking and spine morphology via
      Kalirin-7 overexpression is a fundamental pathogenesis of remifentanil-induced
      hyperalgesia in rats.

PMID- 29578865
TI  - Evaluating Physician Attitudes and Practices Regarding Herpes Zoster Vaccination.
AB  - PURPOSE: To investigate the knowledge, attitudes, and practice patterns of
      primary care physicians regarding administration of the herpes zoster (HZ)
      vaccine at NYU Langone Health (NYULH). METHODS: A cross-sectional online survey
      was distributed from January to March 2017 to all physicians in the Division of
      General Internal Medicine and Clinical Innovation at NYULH across 5 different
      practice settings. RESULTS: The response rate was 26% (138 of 530). Of the
      surveyed physicians, 76% (100/132) agreed that the HZ vaccine was an important
      clinical priority, compared with 93% and 94% for influenza and pneumococcal
      vaccination, respectively (P < 0.001). Only 35% (47/132) strongly agreed that it
      was important, compared with 68% (90/132) and 74% (98/132) who strongly agreed
      that pneumococcal and influenza vaccines, respectively, were important.
      Respondents estimated that 43% of their immunocompetent patients aged 60 or older
      received the HZ vaccine, whereas only 11% of patients aged 50 to 59 received the
      HZ vaccine (P < 0.001). The rate of HZ vaccination was lower in public hospitals
      (26%) than in the NYULH faculty group practice (46%) (P = 0.007). A greater
      percent (67% and 72%) of their patients have received influenza and pneumococcal
      vaccines, respectively (P < 0.001). Almost all doctors (99%, 131/132) consider
      the Centers for Disease Control and Prevention recommendations important in
      determining vaccination practices. CONCLUSIONS: HZ vaccination rates remain
      relatively low compared with rates of influenza and pneumonia vaccination. The
      recommendation for vaccination against zoster by the Centers for Disease Control
      and Prevention for individuals aged 50 years and older and stronger
      recommendations by primary care physicians for administration of zoster vaccines
      are needed to increase HZ vaccination rates.

PMID- 29578866
TI  - Endoscopic ultrasound-guided gallbladder drainage for acute cholecystitis with a
      lumen-apposing metal stent: a systematic review of case series.
AB  - Management of patients with acute cholecystitis unfit for surgery is challenging.
      Recently, endoscopic ultrasound (EUS)-guided gallbladder drainage with a lumen
      apposing metal stent (LAMS) has been introduced for these patients. We performed
      a systematic review and pooled-data analysis in this field. A comprehensive
      review of case series on gallbladder drainage with EUS-guided LAMS placement was
      performed. Only case series with at least five patients were considered. The
      rates of technical success, clinical success, and adverse events were computed.
      Overall, nine case series with a total of 226 patients were identified. The stent
      was positioned successfully in 215 cases [95.1%, 95% confidence interval
      (CI)=92.3-98]. Clinical success was achieved in 207 patients, corresponding to a
      91.6% (95% CI=88-95.2) rate at intention-to-treat analysis and 96.3% (95% CI=93.7
      99) at per-protocol analysis. A total of 24 (10.6%) adverse events occurred,
      including 11 (4.9%) cases during the procedure, and 13 (5.7%) observed at follow
      up (median=6 months; range: 2-12 months). A surgical approach was required in
      only 25% of patients with a major adverse event. No case of procedure-related
      death was reported. EUS-guided LAMS placement for gallbladder drainage in
      patients with acute cholecystitis not suitable for surgery is highly successful
      and acceptably safe.

PMID- 29578867
TI  - The relationship between urinary genistein levels and serum alanine
      aminotransferase levels in adults in the USA: National Health and Nutrition
      Examination Survey 1999-2010.
AB  - BACKGROUND: Genistein, a phytoestrogen with similarities to female sex hormones,
      has been shown to protect against oxidative stress and fibrosis in nonalcoholic
      fatty liver injury in animal studies. However, few studies have examined
      genistein's effects on liver function in humans. PARTICIPANTS AND METHODS: We
      analyzed data from the National Health and Nutrition Examination Survey from 1999
      to 2010. Individuals younger than 21 years, with viral hepatitis, or with serum
      alanine aminotransferase (ALT) at the extremes of distribution (5% on each
      extreme) were excluded. Urinary genistein was normalized by urinary creatinine
      levels. The relationship between normalized urinary genistein (nUG) and serum ALT
      was examined using linear regression models with and without adjustment for
      potential confounders, and the differential effect of sex was examined using an
      interaction term. RESULTS: Of the 9864 participants, 52% were female, 50% were
      White, 24% were elderly, 36% had hypertension, 12% had diabetes, and 8.1% were
      heavy alcohol drinkers. Serum ALT was significantly lower in the highest quartile
      compared with the lowest quartile of nUG (22.3 vs. 23.5 U/l; P<0.001). In
      adjusted models, individuals in the highest quartile had 0.75 U/l lower ALT
      levels than those in the lowest quartile (P=0.02). We found a significant
      difference in ALT levels between the lowest and highest quartiles of nUG in
      males, but not in females (difference in differences=1.77 U/l, interaction
      P=0.04). CONCLUSION: We found a statistically significant association between
      higher nUG and lower serum ALT in males, but not in females. The sex-specific
      role of genistein in mitigating liver disease merits further study.

PMID- 29578868
TI  - Hip Joint Effusion-Synovitis Is Associated With Hip Pain and Sports/Recreation
      Function in Female Professional Ballet Dancers.
AB  - OBJECTIVE: To compare hip joint effusion-synovitis prevalence in professional
      ballet dancers with nondancing athletes and to evaluate the relationship between
      effusion-synovitis and clinical measures and cartilage defects. DESIGN: Case
      control study. SETTING: Elite ballet and sport. PARTICIPANTS: Forty-nine
      professional ballet dancers and 49 age-matched and sex-matched athletes.
      INDEPENDENT VARIABLES: Group (dancers/athletes), sex, age, years of training,
      Copenhagen Hip and Groin Outcome Scores (HAGOSs), hip rotation range of motion
      (ROM), generalized joint hypermobility (GJH), and hip cartilage defect scores.
      MAIN OUTCOME MEASURES: Hip joint effusion-synovitis (absent, grade 1 = 2-4 mm,
      grade 2 = >4 mm) scored with 3-Tesla magnetic resonance imaging. RESULTS: Hip
      joint effusion-synovitis was found in 22 (45%) dancers and 13 (26.5%) athletes (P
      = 0.06). Grade 2 effusion-synovitis was only found in dancers (n = 8, r = 0.31, P
      = 0.009). The prevalence of effusion-synovitis was similar in men (n = 11, 26%)
      and women (n = 24, 43%, P = 0.09). Female dancers with effusion-synovitis had
      lower HAGOS pain (r = 0.63, P = 0.001) and sports/recreation scores (r = 0.66, P
      = 0.001) compared with those without effusion-synovitis. The HAGOS scores were
      not related to effusion-synovitis in male dancers or female and male athletes (P
      > 0.01 for all). Effusion-synovitis was not related to hip ROM, GJH, or cartilage
      defect scores (P > 0.05 for all). CONCLUSIONS: Hip joint effusion-synovitis was
      related to higher levels of pain and lower sports/recreation function in female
      ballet dancers. Effusion-synovitis was not related to hip rotation ROM, GJH or
      cartilage defects. Larger sized joint effusion-synovitis was exclusively found in
      dancers.

PMID- 29578869
TI  - Orthopedic Injuries in Professional Surfers: A Retrospective Study at a Single
      Orthopedic Center.
AB  - BACKGROUND: Literature regarding surfing injuries is scarce and most studies
      report a high number of minor injuries. Recent literature suggests that
      musculoskeletal injuries are more common than previously reported. In the mid
      2000s, competitive surfing has seen an increase in aerial maneuvers, as they have
      become more highly rewarded by the judging panel, which may be contributing to a
      change in injury patterns. Our goal was to evaluate orthopedic injuries in
      professional surfers. HYPOTHESIS: Orthopedic injuries in professional surfers are
      diverse and have evolved with skill and technology. STUDY DESIGN: Retrospective
      observational study. LEVEL OF EVIDENCE: Level 4 Case Series. METHODS: Medical
      records of professional surfers from a single orthopedic center between 1991 and
      2016 were reviewed. Injuries sustained while surfing and chronic injuries related
      to surfing were included. Site of injury, diagnosis, and treatment were recorded
      along with demographic data. RESULTS: In total, 163 injuries in 86 athletes were
      recorded. The median injury age was 28.5 years (range 12-62 years) and 92.6% of
      patients were male. The most frequently injured body parts were the knee (28.2%),
      ankle (22.1%), and shoulder (19%). Most knee injuries were of the medial
      collateral ligament at 49%, with 75% of ankle injuries being sprains, and in
      shoulder, 48% had instability, 42% had a rotator cuff tear, and 35% had a
      superior anterior-posterior labral tear. Lower extremity injuries primarily
      affected the surfers' back leg (72.5%). In all, 34.6% of all injuries required
      surgical intervention and involved shoulder injuries most the time. CONCLUSIONS:
      The most common orthopedic injuries in professional surfers involve the knee,
      ankle, shoulder, hip, and back. Surfers' rear extremities were preferentially
      injured which is the extremity responsible for power and torque. Shoulder
      injuries increased the probability of an operative intervention. Last, overuse
      injuries (femoral-acetabular impingement, rotator cuffs) occurred in the older
      surf population compared with more acute injuries (ankle sprains/fractures,
      anterior cruciate ligament tears) which is also consistent with time to surgery.

PMID- 29578870
TI  - Hepatic Epithelioid Angiomyolipoma and 18F-FDG PET/CT.
AB  - Hepatic epithelioid angiomyolipoma (AML) is rare. Although generally epithelioid
      AML shows benign biological behavior, it can occasionally have malignant
      potential. In this study, we report a case of 2 hepatic epithelioid AMLs with
      different F-FDG uptake; one is intensely FDG avid, and the other is non-FDG avid.

PMID- 29578871
TI  - Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga
      Prostate-Specific Membrane Antigen PET/CT.
AB  - We present here a case of metastatic adrenocortical carcinoma with bilateral lung
      nodules. The patient had been treated with mitotane therapy initially and then
      was later referred for chemotherapy. There was progression of disease noted on
      the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned
      to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed
      peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

PMID- 29578872
TI  - 68Ga-Prostate-Specific Membrane Antigen PET/CT in Triple-Negative Breast Cancer.
AB  - The prostate-specific membrane antigen (PSMA) is a transmembrane protein with
      elevated expression in prostate cancer cells. Breast cancer also shows PSMA
      expression. We present the case of a 30-year-old woman with triple-negative
      bilateral breast carcinoma who underwent bilateral mastectomy, chemotherapy, and
      radiotherapy. She developed a left chest wall and liver recurrence after primary
      therapy. Her recurrent disease was also triple-negative. In view of the known
      poor prognosis and very limited therapeutic options, we performed Ga-PSMA PET/CT
      scan to explore the possibility of PSMA-based therapy as a future option after
      exhausting standard-of-care treatments.

PMID- 29578873
TI  - Unexpected Detection of Bone Metastases on Renal Dynamic Scintigraphy.
AB  - A 57-year-old man with renal mass underwent Tc-diethylenetriaminepentaacetic acid
      renal dynamic scintigraphy for evaluation of renal function. The blood flow phase
      images demonstrated a focus of abnormal increased tracer uptake in the region of
      the right lower quadrant. On the functional phase images, the activity became
      unimpressive gradually. This focus corresponded to an osteolytic lesion in the
      right ilium on the CT and MR images, which was a typical pattern of bone
      metastasis.

PMID- 29578874
TI  - Extradural Arachnoid Cyst Excision.
AB  - Arachnoid cysts are an uncommon postoperative complication and can result in back
      pain, radiculopathy, and/or cauda equina syndrome. For symptomatic postoperative
      arachnoid cysts, surgical management is the accepted treatment. While excision of
      arachnoid cysts is the preferred surgical method, cysts with adhesions to nerve
      roots and/or dura can be treated with cyst fenestration to reduce morbidity of
      excision. Surgeons should be prepared for dural defects after cyst excision,
      which can require dural grafting and lumbar drains for cerebrospinal fluid
      diversion.

PMID- 29578875
TI  - Strategies for the Prevention and Treatment of Surgical Site Infection in the
      Lumbar Spine.
AB  - Surgical site infection (SSI) following spine surgery can be devastating for both
      the patient and the surgeon. It leads to significant morbidity and associated
      health care costs, from readmissions, reoperations, and subsequent poor clinical
      outcomes. Complications associated with SSI following spine surgery include
      pseudarthrosis, neurological deterioration, sepsis, and death. Its management can
      be very challenging. The diagnosis of SSI involves the interpretation of combined
      clinical, laboratory, and occasionally radiologic findings. Most infections can
      be treated with an appropriate course of antibiotics and bracing if required.
      Surgical intervention is usually reserved for infections resistant to medical
      management, the need for open biopsy/culture, evolving spinal instability or
      deformity, and neurologic deficit or deterioration. A thorough knowledge of
      associated risk factors is required and patients should be stratified for risk
      preoperatively. The multifaceted approach of risk stratification, early diagnosis
      and effective treatment, is essential for successful prevention and effective
      treatment and crucial for a satisfactory outcome.

PMID- 29578876
TI  - Surgical Strategies to Prevent Adjacent Segment Disease in the Cervical Spine.
AB  - The most popular approach to treating symptomatic cervical disk disease is
      anterior cervical discectomy and fusion. Although this procedure has significant
      long-term clinical success, it is associated with progressive adjacent segment
      degeneration with an annual incidence of ~3%. Total disk arthroplasty was
      designed as an alternative to fusion that could preserve segmental motion at the
      operative level and potentially delay or prevent adjacent-level breakdown. The
      etiology of adjacent segment pathology (ASP) is multifactorial, and it is likely
      that most cases of ASP are unavoidable. When attempting to surgically prevent
      ASP, it is important to consider nonfusion alternatives, be judicious in one's
      level selection, and attempt to restore sagittal alignment. When ASP becomes a
      clinical problem, it is important to have an algorithm for how best to treat it.

PMID- 29578877
TI  - Thoracolumbar Burst Fractures.
AB  - Thoracolumbar burst fractures are high-energy vertebral injuries, which commonly
      can be treated nonoperatively. Consideration of the injury pattern, extent of
      comminution, neurological status, and integrity of the posterior ligamentous
      complex may help determine whether operative management is appropriate. Several
      classification systems are contingent upon these factors to assist with clinical
      decision-making. A multitude of operative procedures have been shown to have good
      radiographic and clinical outcomes with extended follow-up, and treatment choice
      should be based on the individual's clinical and radiographic presentation.

PMID- 29578878
TI  - Intra-Abdominal Hypertension Is More Common Than Previously Thought: A
      Prospective Study in a Mixed Medical-Surgical ICU.
AB  - OBJECTIVES: To determine the prevalence of intra-abdominal hypertension in mixed
      medical-surgical critically ill patients using modern definitions and measurement
      techniques. Secondarily to determine variables associated with intra-abdominal
      hypertension and ICU mortality. DESIGN: A prospective observational study.
      SETTING: Single institution trauma, medical and surgical ICU in Canada. PATIENTS:
      Consecutive adult patients admitted to the ICU (n = 285). INTERVENTION: Intra
      abdominal pressure measurements twice a day during admission to the ICU.
      MEASUREMENTS AND MAIN RESULTS: In 285 patients who met inclusion criteria, 30%
      were diagnosed with intra-abdominal hypertension at admission and a further 15%
      developed intra-abdominal hypertension during admission. The prevalence of
      abdominal compartment syndrome was 3%. Obesity, sepsis, mechanical ventilation,
      and 24-hour fluid balance (> 3 L) were all independent predictors for intra
      abdominal hypertension. Intra-abdominal hypertension occurred in 28% of
      nonventilated patients. Admission type (medical vs surgical vs trauma) was not a
      significant predictor of intra-abdominal hypertension. Overall ICU mortality was
      20% and was significantly higher for patients with intra-abdominal hypertension
      (30%) compared with patients without intra-abdominal hypertension (11%). Intra
      abdominal hypertension of any grade was an independent predictor of mortality
      (odds ratio, 3.33; 95% CI, 1.46-7.57). CONCLUSIONS: Intra-abdominal hypertension
      is common in both surgical and nonsurgical patients in the intensive care setting
      and was found to be independently associated with mortality. Despite prior
      reports to the contrary, intra-abdominal hypertension develops in nonventilated
      patients and in patients who do not have intra-abdominal hypertension at
      admission. Intra-abdominal pressure monitoring is inexpensive, provides valuable
      clinical information, and there may be a role for its routine measurement in the
      ICU. Future work should evaluate the impact of early interventions for patients
      with intra-abdominal hypertension.

PMID- 29578879
TI  - What Faces Reveal: A Novel Method to Identify Patients at Risk of Deterioration
      Using Facial Expressions.
AB  - OBJECTIVES: To identify facial expressions occurring in patients at risk of
      deterioration in hospital wards. DESIGN: Prospective observational feasibility
      study. SETTING: General ward patients in a London Community Hospital, United
      Kingdom. PATIENTS: Thirty-four patients at risk of clinical deterioration.
      INTERVENTIONS: A 5-minute video (25 frames/s; 7,500 images) was recorded,
      encrypted, and subsequently analyzed for action units by a trained facial action
      coding system psychologist blinded to outcome. MEASUREMENTS AND MAIN RESULTS:
      Action units of the upper face, head position, eyes position, lips and jaw
      position, and lower face were analyzed in conjunction with clinical measures
      collected within the National Early Warning Score. The most frequently detected
      action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for
      head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%)
      for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of
      certain combined face displays was increased in patients requiring admission to
      intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013),
      action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 +
      15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2,
      and face display 3 increased the risk of being admitted to intensive care eight
      fold, 18-fold, and as a sure event, respectively. A logistic regression model
      with face display 1, face display 2, face display 3, and National Early Warning
      Score as independent covariates described admission to intensive care with an
      average concordance statistic (C-index) of 0.71 (p = 0.009). CONCLUSIONS:
      Patterned facial expressions can be identified in deteriorating general ward
      patients. This tool may potentially augment risk prediction of current scoring
      systems.

PMID- 29578880
TI  - A strategy utilizing ambulatory monitoring and home and clinic blood pressure
      measurements to optimize the safety evaluation of noncardiovascular drugs with
      potential for hemodynamic effects: a report from the SYNERGY trial.
AB  - OBJECTIVE: The aim of this study was to perform a blood pressure (BP) safety
      evaluation in patients with an overactive bladder receiving solifenacin (an
      antimuscarinic agent), mirabegron (a beta3-adrenoceptor agonist), or both
      compared with placebo in the SYNERGY trial. PATIENTS AND METHODS: Patients were
      randomized to receive solifenacin 5 mg+mirabegron 50 mg (combination 5+50 mg);
      solifenacin 5 mg+mirabegron 25 mg (combination 5+25 mg); solifenacin 5 mg;
      mirabegron 50 mg; mirabegron 25 mg; or placebo for a double-blind 12-week
      treatment period. Systolic BP, diastolic BP, and heart rate were measured by
      ambulatory BP monitoring, and in the clinic or home. RESULTS: A total of 715
      patients were analyzed in an ambulatory BP monitoring substudy. At the end of
      treatment, ambulatory BP monitoring measurements showed no consistent increases
      from baseline in the mean 24-h systolic BP or diastolic BP for combination versus
      monotherapy groups or for monotherapy groups versus placebo. Analysis of 1-h BP
      averages during the 6 h range that included the Tmax values of both study drugs
      showed no significant BP effects. Shift analysis (switch between different
      normotension/hypertension stages) did not show differences among the active and
      placebo groups, nor did outlier analysis of major BP changes differ between
      placebo and active treatment. Similarly, there were no significant signals in the
      24-h heart rate. Office and home measurements were consistent with ambulatory BP
      monitoring findings. CONCLUSIONS: A paradigm of ambulatory BP monitoring analysis
      designed to test BP safety of noncardiovascular drugs showed that solifenacin
      plus mirabegron combination therapy during 12 weeks produced no meaningful
      changes in BP or heart rate.

PMID- 29578881
TI  - Aggressive Digital Papillary Adenocarcinoma: Population-Based Analysis of
      Incidence, Demographics, Treatment, and Outcomes.
AB  - BACKGROUND: As a rare cutaneous malignancy, epidemiologic and outcomes data for
      aggressive digital papillary adenocarcinoma (ADPA) are limited and no treatment
      guidelines exist. OBJECTIVE: To provide a population-based study of ADPA
      incidence and outcomes with a subgroup comparison of patients with localized
      versus regional disease. METHODS: Data from 18 registries within the National
      Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program
      were examined for patients with ADPA (1995-2013) to provide demographic- and
      cancer-related information, and to calculate race- and age-specific rate ratios,
      incidence, and mortality. Patients were stratified by the stage for further
      comparison. RESULTS: Ninety-four cases of ADPA were identified. Overall, ADPA
      incidence was 0.08 per 1,000,000 person-years, 4 times higher in males than in
      females (0.13 vs 0.03, p < .001), and most common in Caucasians. Regional disease
      spread occurred in 22.3% of patients and disease-specific mortality in 2.1% of
      patients. Patients with regional versus localized disease at diagnosis did not
      differ significantly in sex, age, race, primary site, tumor size, or mortality.
      CONCLUSION: Aggressive digital papillary adenocarcinoma is a rare malignancy with
      increasing incidence. Regional disease spread is not infrequent, but mortality is
      rare. Identification of patients best suited for additional diagnostic procedures
      or more extensive surgical resection remains challenging.

PMID- 29578882
TI  - Basal Cell Carcinoma Arising at the Site of a Lip Piercing.

PMID- 29578883
TI  - Skin and Soft Tissue Surgery in the Office Versus Operating Room Setting: An
      Analysis Based on Individual-Level Medicare Data.
AB  - BACKGROUND: The relative volume of skin and soft tissue excision and
      reconstructive procedures performed in the outpatient office versus facility
      (ambulatory surgical center or hospital) differs by specialty, and has major
      implications for quality of care, outcomes, development of guidelines, resident
      education, health care economics, and patient perception. OBJECTIVE: To assess
      the relative volume of surgical procedures performed in each setting (office vs
      ambulatory surgery center [ASC]/hospital) by dermatologists and
      nondermatologists. METHODS: A cross-sectional analytical study was performed
      using the Medicare public use file (PUF) for 2014, which includes every patient
      seen in an office, ASC, or hospital in the United States billed to Medicare part
      B. Data were divided by physician specialty and setting. RESULT: A total of
      9,316,307 individual encounters were included in the Medicare PUF. Dermatologists
      account for 195,001 (2.1%) of the total. Dermatologists were more likely to
      perform surgical procedures in an office setting only (odds ratio 5.48 [95%
      confidence interval 5.05-5.95], p < .0001) than other specialists in aggregate.
      CONCLUSION: More than 90% of surgical procedures are performed in an office
      setting, and dermatologists are more than 5 times as likely as other specialists
      to operate in an office setting.

PMID- 29578884
TI  - Impact of Muir-Torre Syndrome on Survival in Patients With Sebaceous Carcinoma: A
      SEER Population-Based Study.

PMID- 29578885
TI  - Analysis of Opioid Use Following Curative Cancer Treatment at a Large Urban
      Safety-net Hospital.
AB  - OBJECTIVES: This study examined the pattern of use and factors predicting
      prolonged prescription opioid medications among cancer patients following
      treatment with curative intent. MATERIALS AND METHODS: Patients diagnosed with
      cancer over a 3-year period at a large urban safety-net hospital were included.
      Univariate and multivariate analyses was used to identify factors associated with
      continued opioid use. RESULTS: Of the 199 patients included in the study, 38%
      continued to receive an opioid prescription well beyond the acute diagnosis and
      treatment phase. Mean age was 60.3 years, with a female preponderance (63%).
      Surgical resection only (31.6%) and the combination of surgery, chemotherapy, and
      radiation (19.7%) were the commonest treatment modalities. Pain-related
      comorbidities predating cancer diagnosis were reported in 53.3% of the patients,
      and about 33% were also on pain-modifying medications (odds ratio [OR], 3.58; 95%
      confidence interval [CI], 1.92-6.77; Fisher exact test P<0.001). Average number
      of prescriptions received per patient was 4.8 (range, 1 to 31), over an average
      of 9.5 months (range, 1.2 to 28.1 mo). Mean morphine milligram equivalents
      prescribed per prescription was 319 mg (range, 48 to 2475 mg). According to
      multivariate model, patients who received chemotherapy (OR, 7.25; 95% CI, 2.09
      25.17; P=0.0018), or pain-modifying medications (OR, 4.61; 95% CI, 2.25-9.44;
      P<0.0001) were significantly more likely to continue to receive prescriptions for
      opioids. DISCUSSION: Treatment with chemotherapy, pain-modifying medications,
      cancer stage, and interval between diagnosis and treatment are the best
      predictors for continuous opioid use. The current epidemic of opioid misuse and
      abuse makes examination current practices and identifification of areas of
      improvement imperative.

PMID- 29578886
TI  - Development of a Novel Bone Conduction Verification Tool Using a Surface
      Microphone: Validation With Percutaneous Bone Conduction Users.
AB  - OBJECTIVES: To determine if a newly-designed, forehead-mounted surface microphone
      would yield equivalent estimates of audibility when compared to audibility
      measured with a skull simulator for adult bone conduction users. DESIGN: Data was
      analyzed using a within subjects, repeated measures design. There were two
      different sensors (skull simulator and surface microphone) measuring the same
      hearing aid programmed to the same settings for all subjects. We were looking for
      equivalent results. PATIENTS: Twenty-one adult percutaneous bone conduction users
      (12 females and 9 males) were recruited for this study. Mean age was 54.32 years
      with a standard deviation of 14.51 years. Nineteen of the subjects had
      conductive/mixed hearing loss and two had single-sided deafness. METHODS: To
      define audibility, we needed to establish two things: (1) in situ-level
      thresholds at each audiometric frequency in force (skull simulator) and in sound
      pressure level (SPL; surface microphone). Next, we measured the responses of the
      preprogrammed test device in force on the skull simulator and in SPL on the
      surface mic in response to pink noise at three input levels: 55, 65, and 75 dB
      SPL. The skull simulator responses were converted to real head force responses by
      means of an individual real head to coupler difference transform. Subtracting the
      real head force level thresholds from the real head force output of the test aid
      yielded the audibility for each audiometric frequency for the skull simulator.
      Subtracting the SPL thresholds from the surface microphone from the SPL output of
      the test aid yielded the audibility for each audiometric frequency for the
      surface microphone. The surface microphone was removed and retested to establish
      the test-retest reliability of the tool. RESULTS: We ran a 2 (sensor) * 3 (input
      level) * 10 (frequency) mixed analysis of variance to determine if there were any
      significant main effects and interactions. There was a significant three-way
      interaction, so we proceeded to explore our planned comparisons. There were 90
      planned comparisons of interest, three at each frequency (3 * 10) for the three
      input levels (30 * 3). Therefore, to minimize a type 1 error associated with
      multiple comparisons, we adjusted alpha using the Holm-Bonferroni method. There
      were five comparisons that yielded significant differences between the skull
      simulator and surface microphone (test and retest) in the estimation of
      audibility. However, the mean difference in these effects was small at 3.3 dB.
      Both sensors yielded equivalent results for the majority of comparisons.
      CONCLUSIONS: Models of bone conduction devices that have intact skin cannot be
      measured with the skull simulator. This study is the first to present and
      evaluate a new tool for bone conduction verification. The surface microphone is
      capable of yielding equivalent audibility measurements as the skull simulator for
      percutaneous bone conduction users at multiple input levels. This device holds
      potential for measuring other bone conduction devices (Sentio, BoneBridge,
      Attract, Soft headband devices) that do not have a percutaneous implant.

PMID- 29578887
TI  - Visual Performance and Perception as a Target of Saccadic Strategies in Patients
      With Unilateral Vestibular Loss.
AB  - OBJECTIVES: To evaluate the ability of saccadic strategies developed during
      vestibular compensation to reduce the effect of an impaired vestibulo-ocular
      reflex (VOR) on a retinal smear and image motion sensation. DESIGN: Twenty
      patients with unilateral vestibular loss were examined with a video head impulse
      test before and after vestibular rehabilitation (VR) with the use of gaze
      stabilization and refixation saccades training. Head and eye velocity functions
      were processed to infer the retinal eccentricity, and through its correlation
      with visual acuity (VA), several measurements are proposed to evaluate the
      influence of VR on saccades behavior and visual performance. To isolate the
      effect of saccades on the findings and avoid bias because of gain differences,
      only patients whose VOR gain values remained unchanged after VR were included.
      RESULTS: Improved contribution of covert saccades and reduction of overt saccades
      latency were measured after VR. We found significant differences when assessing
      both the interval less than 70% VA (50.25 ms), which is considered the limit of a
      moderate low vision, and less than 50% VA (39.515 ms), which is the limit for
      severe low vision. Time to recover a VA of 75% (near normal) was reduced in all
      the patients (median: 56.472 ms). CONCLUSION: Despite the absence of VOR gain
      improvement, patients with unilateral vestibular loss are able to develop
      saccadic strategies that allow the shortening of the interval of retinal smear
      and image motion. The proposed measurements might be of use to evaluate VR
      outcomes and visually induced impairment.

PMID- 29578888
TI  - Occupational Contact Dermatitis in the Canadian Aircraft Industry: A 25-Year
      Retrospective Study.
AB  - BACKGROUND: Aircraft building exposes workers to irritant and sensitizing
      products. OBJECTIVE: The aim of this article was to study occupational dermatoses
      among aircraft workers over 25 years. METHODS: The files of aerospace workers
      referred between 1990 and 2015 were extracted from the database of the McGill
      University Health Centre contact dermatitis clinic. These were subdivided
      according to demographics, type of work, patch testing results, and final
      diagnosis. RESULTS: Of 305 workers, 58% were 40 years or younger; one third were
      women. Onset of dermatitis varied from 2 months to 25 years, but 120 cases (39%)
      occurred during the first 3 years. Fifty-one percent of the cases involved
      assemblers, and 27% were composite material technicians, which were
      overrepresented as they constitute 10% of the workforce. Of the 305 workers, 152
      suffered from allergic contact dermatitis, and 96 had irritant contact
      dermatitis. Of those with allergic contact dermatitis, 124 reacted to epoxy-based
      workplace products, but only 48 had positive patch tests to commercially
      available epoxy allergens. CONCLUSION: More than 60% of the cases of epoxy
      allergy would have been missed without testing with workplace products.

PMID- 29578889
TI  - Statistics Commentary Series: Commentary No. 26: Dealing With Outliers.

PMID- 29578890
TI  - Static and Dynamic Pupillary Characteristics in Clinically Unilateral
      Pseudoexfoliation Syndrome.
AB  - PURPOSE: The purpose of this study was to perform a comparison of static and
      dynamic pupillometry measurements in patients with clinically unilateral
      pseudoexfoliation syndrome (PES) and age-matched controls. METHODS: This
      prospective cross-sectional study consisted of 38 patients with unilateral PES
      and 40 control participants. A quantitative pupillometry system was used to
      evaluate the pupil characteristics of eyes with PES (group 1), clinically
      unaffected fellow eyes (group 2), and healthy eyes (group 3). Static pupillometry
      measurements including scotopic pupil diameter (PD), mesopic PD, low photopic PD,
      and high photopic PD were undertaken. Subsequently, dynamic pupillometry
      measurements including resting diameter, amplitude of pupil contraction, latency
      of pupil contraction, duration of pupil contraction, velocity of pupil
      contraction, latency of pupil dilation, duration of pupil dilation, and velocity
      of pupil dilation were undertaken. RESULTS: There were statistically significant
      differences between the groups with regard to scotopic PD, mesopic PD, and low
      photopic PD (P<0.001). The pairwise comparisons exhibited that group 1 shows
      significantly lower PD values compared with groups 2 and 3. Group 2 also had
      significantly lower PD values compared with group 3. In addition, groups 1 and 2
      had statistically significantly lower values of amplitude of pupil contraction,
      velocity of pupil contraction, duration of pupil dilatation, and velocity of
      pupil dilatation values compared with group 3. Moreover, group 1 and 2
      demonstrated statistically significantly prolonged latency of pupil dilatation
      compared with group 3. CONCLUSIONS: Static and dynamic pupil characteristics of
      affected eyes and their fellow eyes of cases with unilateral PES are different
      from the healthy subjects.

PMID- 29578891
TI  - Diagnostic Abilities of the Optical Microangiography Parameters of the 3*3 mm and
      6*6 mm Macular Scans in Glaucoma.
AB  - PURPOSE: To evaluate the diagnostic abilities of macular vessel length and
      perfusion densities measured with optical microangiography (OMAG) over a 3*3 mm
      and a 6*6 mm region, and to compare these with macular ganglion cell-inner
      plexiform layer (GCIPL) thickness in eyes with primary open-angle glaucoma
      (POAG). METHODS: In a cross-sectional study, 96 eyes of 57 control subjects and
      88 eyes of 57 POAG patients underwent macular imaging with optical coherence
      tomography. Area under receiver operating characteristic curves (AUC) and
      sensitivities at 90% specificity of OMAG and GCIPL parameters were evaluated.
      RESULTS: Most OMAG parameters of the 3*3 mm macular scan and all inner sector
      parameters of the 6*6 mm scan were similar (P>0.05) in the POAG and control eyes.
      All outer sector OMAG parameters of the 6*6 mm scan were significantly less
      (P<0.05) in the POAG eyes. AUC and sensitivity at 90% specificity of the best
      parameter of the 3*3 mm OMAG scan (inner temporal vessel length density; 0.65%
      and 26%, respectively) were statistically similar (P>0.05) to that of the 6*6 mm
      scan (outer inferior vessel length density; 0.72% and 30%, respectively). AUC and
      sensitivity of the best GCIPL thickness parameter (inferotemporal GCIPL
      thickness, 0.84% and 67%) were significantly better (P<0.05) than that of the
      vessel length densities. CONCLUSIONS: The outer sector measurements of the 6*6 mm
      macular OMAG scans seem to be better than the inner sector measurements in
      diagnosing glaucoma. The GCIPL thickness measurements were significantly better
      than all macular OMAG parameters in diagnosing glaucoma.

PMID- 29578892
TI  - Comparison of Efficacy and Complications of Cyclophotocoagulation and Second
      Glaucoma Drainage Device After Initial Glaucoma Drainage Device Failure.

PMID- 29578893
TI  - In Reply: Comparison of Efficacy and Complications of Cyclophotocoagulation and
      Second Glaucoma Drainage Device After Initial Glaucoma Drainage Device Failure.

PMID- 29578894
TI  - Comparison of Placental and Neonatal Admission Complete Blood Cell Count and
      Blood Cultures.
AB  - BACKGROUND: The utilization of placental blood for neonatal admission laboratory
      tests, specifically the complete blood cell (CBC) count and blood culture, has
      the potential to delay the onset of anemia of prematurity and intraventricular
      hemorrhage, frequency of blood transfusions and associated complications, and
      painful procedures related to laboratory sampling. PURPOSE: To determine the
      feasibility of drawing neonatal admission laboratory tests from the placenta
      rather than the neonate and to compare CBC count and blood culture results.
      METHODS: All infants less than 35 weeks' gestational age and all term infants
      with a maternal history of chorioamnionitis or untreated, positive group B
      Streptococcus status were eligible to participate. Participating infants had
      paired CBC count and blood cultures obtained from the placenta and the infant.
      RESULTS: All CBC count outcomes were significantly, positively correlated between
      placental and infant blood (all Ps < .05). The paired white blood cells,
      neutrophils, and lymphocytes were strongly correlated (r = 0.761, r = 0.797, and
      r = 0.815, respectively), whereas the hemoglobin, hematocrit, platelet, and
      eosinophils were moderately correlated (r = 0.554, r = 0.545, r = 0.563, and r =
      0.478, respectively). Monocytes and basophils were only weakly correlated (r =
      0.373 and r = 0.217, respectively). There were 13 (93%) pairs where placental
      blood culture was positive but the direct infant draw blood culture was negative,
      and 1 (7%) pair where the placental culture was negative but the direct infant
      draw blood culture was positive. IMPLICATIONS FOR PRACTICE: The results of this
      and other studies suggest that placental blood can be reliably used to obtain
      neonatal admission CBC count and blood cultures. IMPLICATIONS FOR RESEARCH:
      Further research is needed regarding the prevention of blood culture
      contamination, especially in vaginally delivered placentas. Institutions that
      adopt this procedure should perform quality improvement initiatives to monitor
      outcomes and add to the growing body of literature on the utilization of
      placental blood for neonatal admission laboratory tests.

PMID- 29578895
TI  - Concerns about a study on sexually transmitted infections after initiation of HIV
      preexposure prophylaxis.

PMID- 29578896
TI  - Herniation of Hoffa's Fat Pad Through the Lateral Retinaculum: Usefulness of
      Dynamic Ultrasonography to Diagnose a Lateral Knee Mass.

PMID- 29578897
TI  - Development and Validation of the Realistic Anthropomorphic Flexible (RAF)
      Phantom.
AB  - Voxel phantoms developed by segmenting computed tomography images are known to be
      more anatomically accurate than mathematical phantoms. However, due to their lack
      of flexibility and the complexity of voxel datasets, the use of voxel phantoms in
      dosimetry is often impractical. This paper describes the development of the
      realistic anthropomorphic flexible (RAF) polygonal mesh phantom, a novel phantom
      based on Boundary Representation (B-Rep) that merges anatomical accuracy and
      flexibility. Rather than using segmentation of tomography images, the modeling of
      the phantom's organs was based on freely and commercially available anatomical
      atlases, ICRP 89, and recent medical literature. To validate the phantom, a high
      resolution voxel version was created for the MCNPx transport code. The voxelized
      RAF phantom was validated by comparing it with the ICRP 110 male phantom for
      external irradiations with parallel beams of photons and electrons. Dose
      coefficients obtained from simulations with the RAF phantom were compared with
      those from ICRP Publication 116. Relevant differences in organ doses were found.

PMID- 29578898
TI  - Reassessment of Resuspension Factor Following Radionuclide Dispersal: Toward a
      General-purpose Rate Constant.
AB  - A recent analysis of historical radionuclide resuspension datasets confirmed the
      general applicability of the Anspaugh and modified Anspaugh models of
      resuspension factors following both controlled and disastrous releases. While
      observations appear to have larger variance earlier in time, previous studies
      equally weighted the data for statistical fit calculations; this could induce a
      positive skewing of resuspension coefficients in the early time-period. A
      refitting is performed using a relative instrumental weighting of the
      observations. Measurements within a 3-d window are grouped into singular sample
      sets to construct standard deviations. The resulting best-fit equations produce
      tamer exponentials, which give decreased integrated resuspension factor values
      relative to those reported by Anspaugh. As expected, the fits attenuate greater
      error among the data at earlier time. The reevaluation provides a sharper
      contrast between the empirical models and reaffirms their deficiencies in the
      short-lived timeframe wherein the dynamics of particulate dispersion dominate the
      resuspension process.

PMID- 29578899
TI  - Saving Lives and Preventing Injuries From Unjustified Protective Actions-Method
      for Developing a Comprehensive Public Protective Action Strategy for a Severe NPP
      Emergency.
AB  - During the response to the Fukushima Daiichi nuclear power plant (FDNPP)
      emergency, about 50 patients died during or shortly after an evacuation when they
      were not provided with the needed medical support. In addition, it has been shown
      that during the FDNPP emergency there were increases in mortality rates among the
      elderly due to long-term dislocation as a result of evacuation and relocation
      orders and an inability to stay in areas where residents were advised to shelter
      for extended periods. These deaths occurred even though the possible radiation
      exposure to the public was too low to result in radiation-induced deaths,
      injuries, or a meaningful increase in the cancer rate, even if no protective
      actions had been taken. These problems are not unique to the FDNPP emergency and
      would be expected if the recommendations of many organizations were followed.
      Neither the International Commission on Radiological Protection (ICRP), the U.S.
      Nuclear Regulatory Commission (NRC) nor the U.S Environmental Protection Agency
      (EPA) adequately take into consideration in their recommendations and analysis
      the non-radiological health impacts, such as deaths and injuries, that could
      result from protective actions. Furthermore, ICRP, NRC, EPA, and the U.S.
      Department of Homeland Security (DHS) call for taking protective actions at doses
      lower than those resulting in meaningful adverse radiation-induced health effects
      and do not state the doses at which such effects would be seen. Consequently, it
      would be impossible for decision makers and the public to balance all the hazards
      both from radiation exposure and protective actions when deciding whether a
      protective action is justified. What is needed, as is presented in this paper, is
      a method for developing a comprehensive protective action strategy that allows
      the public, decision makers, and others who must work together to balance the
      radiological with the non-radiological health hazards posed by protective
      actions, and to counter the exaggerated fear of radiation exposure that could
      lead to taking unjustified protective actions and adverse psychological,
      sociological, and other effects.

PMID- 29578900
TI  - Joint American Nuclear Society and Health Physics Society Conference:
      Applicability of Radiation Response Models to Low Dose Protection Standards.
AB  - Seventy-five years after the Hanford Site was initially created as the primary
      plutonium production site for atomic weapons development under the Manhattan
      Project, the American Nuclear Society and the Health Physics Society are
      sponsoring a conference from 30 September through 3 October 2018, in Pasco,
      Washington, titled "Applicability of Radiation Response Models to Low Dose
      Protection Standards." The goal of this conference is to use current scientific
      data to update the approach to regulating low-level radiation doses; i.e., to
      answer a quintessential question of radiation protection-how to best develop
      radiation protection standards that protect human populations against detrimental
      effects while allowing the beneficial uses of radiation and radioactive
      materials. Previous conferences (e.g., "Wingspread Conference," "Arlie
      Conference") have attempted to address this question; but now, almost 20 y later,
      the key issues, goals, conclusions, and recommendations of those two conferences
      remain and are as relevant as they were then. Despite the best efforts of the
      conference participants and increased knowledge and understanding of the science
      underlying radiation effects in human populations, the bases of current radiation
      protection standards have evolved little. This 2018 conference seeks to provide a
      basis and path forward for evolving radiation protection standards to be more
      reflective of current knowledge and understanding of low dose response models.

PMID- 29578901
TI  - A Discussion of the Relative Merits of Evacuation of Persons With Health Care
      Needs.

PMID- 29578902
TI  - Reply to Belcuore.

PMID- 29578903
TI  - Acceptance Testing of Thermoluminescent Dosimeter Holders.
AB  - The U.S. Navy uses the Harshaw 8840/8841 dosimetric (DT-702/PD) system, which
      employs LiF:Mg,Cu,P thermoluminescent dosimeters (TLDs), developed and produced
      by Thermo Fisher Scientific (TFS). The dosimeter consists of four LiF:Mg,Cu,P
      elements, mounted in Teflon(r) on an aluminum card and placed in a plastic
      holder. The holder contains a unique filter for each chip made of copper,
      acrylonitrile butadiene styrene (ABS), Mylar(r), and tin. For accredited
      dosimetry labs, the ISO/IEC 17025:2005(E) requires an acceptance procedure for
      all new equipment. The Naval Dosimetry Center (NDC) has developed and tested a
      new non-destructive procedure, which enables the verification and the evaluation
      of embedded filters in the holders. Testing is based on attenuation measurements
      of low-energy radiation transmitted through each filter in a representative
      sample group of holders to verify that the correct filter type and thickness are
      present. The measured response ratios are then compared with the expected
      response ratios. In addition, each element's measured response is compared to the
      mean response of the group. The test was designed and tested to identify
      significant nonconformities, such as missing copper or tin filters, double copper
      or double tin filters, or other nonconformities that may impact TLD response
      ratios. During the implementation of the developed procedure, testing revealed a
      holder with a double copper filter. To complete the evaluation, the impact of the
      nonconformities on proficiency testing was examined. The evaluation revealed
      failures in proficiency testing categories III and IV when these dosimeters were
      irradiated to high-energy betas.

PMID- 29578904
TI  - The use of National Weather Service Data to Compute the Dose to the MEOI.
AB  - The Turner method is the "benchmark method" for computing the stability class
      that is used to compute the X/Q (s m). The Turner method should be used to
      ascertain the validity of X/Q results determined by other methods. This paper
      used site-specific meteorological data obtained from the National Weather
      Service. The Turner method described herein is simple, quick, accurate, and
      transparent because all of the data, calculations, and results are visible for
      verification and validation with published literature.

PMID- 29578907
TI  - Technical Performance as a Predictor of Clinical Outcomes in Laparoscopic Gastric
      Cancer Surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      technical performance and patient outcomes in laparoscopic gastric cancer
      surgery. BACKGROUND: Laparoscopic gastrectomy for cancer is an advanced procedure
      with high rate of postoperative morbidity and mortality. Many variables including
      patient, disease, and perioperative management factors have been shown to impact
      postoperative outcomes; however, the role of surgical performance is
      insufficiently investigated. METHODS: A retrospective review was performed for
      all patients who had undergone laparoscopic gastrectomy for cancer at 3 teaching
      institutions between 2009 and 2015. Patients with available, unedited video
      recording of their procedure were included in the study. Video files were rated
      for technical performance, using Objective Structured Assessments of Technical
      Skills (OSATS) and Generic Error Rating Tool instruments. The main outcome
      variable was major short-term complications. The effect of technical performance
      on patient outcomes was assessed using logistic regression analysis with backward
      selection strategy. RESULTS: Sixty-one patients with available video recordings
      were included in the study. The overall complication rate was 29.5%. The mean
      Charlson comorbidity index, type of procedure, and the global OSATS score were
      included in the final predictive model. Lower performance score (OSATS <=29)
      remained an independent predictor for major short-term outcomes (odds ratio
      6.49), while adjusting for comorbidities and type of procedure. CONCLUSIONS:
      Intraoperative technical performance predicts major short-term outcomes in
      laparoscopic gastrectomy for cancer. Ongoing assessment and enhancement of
      surgical skills using modern, evidence-based strategies might improve short-term
      patient outcomes. Future work should focus on developing and studying the
      effectiveness of such interventions in laparoscopic gastric cancer surgery.

PMID- 29578909
TI  - 3D Modeling of the Anorectum in Fistulous Crohn's Disease: Long Overdue.

PMID- 29578908
TI  - Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic
      Ductal Adenocarcinoma.
AB  - OBJECTIVES: To establish an evidence-based cutoff to differentiate between early
      and late recurrence and to compare clinicopathologic risk factors between the two
      groups. SUMMARY BACKGROUND DATA: A clear definition of "early recurrence" after
      pancreatic ductal adenocarcinoma resection is currently lacking. METHODS:
      Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between
      2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and
      incomplete follow-up. A minimum P-value approach was used to evaluate the optimal
      cut-off value of recurrence-free survival to divide the patients into early and
      late recurrence cohorts based on subsequent prognosis. Potential risk factors for
      early recurrence were assessed with logistic regression models. RESULTS: Of 957
      included patients, 204 (21.3%) were recurrence-free at last follow-up. The
      optimal length of recurrence-free survival to distinguish between early (n = 388,
      51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients
      with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and
      6% compared with 45 and 22% for the late recurrence group (both P < 0.001).
      Preoperative risk factors for early recurrence included a Charlson age
      comorbidity index >=4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR
      1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of
      poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion
      (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38).
      Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated
      with a reduced likelihood of early recurrence. CONCLUSION: A recurrence-free
      interval of 12 months is the optimal threshold for differentiating between early
      and late recurrence, based on subsequent prognosis.

PMID- 29578910
TI  - Multisource Evaluation of Surgeon Behavior is Associated with Malpractice Claims.
AB  - OBJECTIVE: We merged direct, multisource, and systematic assessments of surgeon
      behavior with malpractice claims, to analyze the relationship between surgeon 360
      degree reviews and malpractice history. BACKGROUND: Previous work suggests that
      malpractice claims are associated with a poor physician-patient relationship,
      which is likely related to behaviors captured by 360-degree review. We
      hypothesize that 360-degree review results are associated with malpractice
      claims. METHODS: Surgeons from 4 academic medical centers covered by a common
      malpractice carrier underwent 360-degree review in 2012 to 2013 (n = 385).
      Matched, de-identified reviews and malpractice claims data were available for 264
      surgeons from 2000 to 2015. We analyzed 23 questions, highlighting positive and
      negative behaviors within the domains of education, excellence, humility,
      openness, respect, service, and teamwork. Regression analysis with robust
      standard error was used to assess the potential association between 360-degree
      review results and malpractice claims. RESULTS: The range of claims among the 264
      surgeons was 0 to 8, with 48.1% of surgeons having at least 1 claim. Multiple
      positive and negative behaviors were significantly associated with the risk of
      having malpractice claims (P < 0.05). Surgeons in the bottom decile for several
      items had an increased likelihood of having at least 1 claim. CONCLUSION: Surgeon
      behavior, as assessed by 360-degree review, is associated with malpractice
      claims. These findings highlight the importance of teamwork and communication in
      exposure to malpractice. Although the nature of malpractice claims is complex and
      multifactorial, the identification and modification of negative physician
      behaviors may mitigate malpractice risk and ultimately result in the improved
      quality of patient care.

PMID- 29578911
TI  - Adrenal Metastasectomy in the Presence and Absence of Extraadrenal Metastatic
      Disease.
AB  - OBJECTIVE: To determine if there are differences in overall survival (OS) or
      event-free survival (EFS) in patients with and without concomitant extra-adrenal
      metastases undergoing adrenal metastasectomy. BACKGROUND: There is growing
      interest in the use of local therapies in patients with oligometastatic disease.
      Previously published series have indicated that long-term survival is possible
      with resection. Adrenalectomy has been used to treat adrenal metastases in select
      patients. METHODS: Patients who underwent adrenal metastasectomy from 1994 to
      2015 were identified from a prospectively maintained institutional database of
      adrenalectomy patients, excluding adrenalectomies due to tumor extension or for
      palliation. Sites of disease, treatment history, and survival data were extracted
      from chart review. RESULTS: One hundred seventy-four patients were included.
      Tumor histology included 68 nonsmall cell lung cancer, 34 renal cancer, 18
      colorectal cancer, 11 melanoma cancer, 10 hepatocellular cancer, 8 sarcoma
      cancer, and 25 other cancers. The median follow-up among survivors was 5.2 (1-21)
      years. OS at 3 and 5 years was 50% and 40%, respectively. Patients with (n = 83)
      and without (n = 91) extra-adrenal metastases did not differ with respect to age,
      adrenal tumor size, or margin status. Median OS (3.3 years for patients with
      concomitant extra-adrenal metastases and 3.0 years for patients with isolated
      adrenal metastases; P = 0.816) and EFS (9.39 vs 9.59 months; P = 0.87) were
      similar. Factors negatively associated with OS included adrenal tumor size (P <
      0.01), renal primary versus other (P < 0.01), and adrenal margin status (P <
      0.01). CONCLUSIONS: In selected patients undergoing adrenal metastasectomy, there
      were no significant differences in OS or EFS between patients with and without
      concomitant extra-adrenal metastases.

PMID- 29578913
TI  - A Changing Landscape in Pancreatic Cancer.

PMID- 29578912
TI  - Stent Design Affects Femoropopliteal Artery Deformation.
AB  - BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is
      multifactorial, and severe FPA deformations occurring with limb flexion are
      likely involved. Different stent designs result in dissimilar stent-artery
      interactions, but the degree of these effects in the FPA is insufficiently
      understood. OBJECTIVES: To determine how different stent designs affect limb
      flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into
      n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT
      images were acquired with limbs in the standing, walking, sitting, and gardening
      postures. Image analysis allowed measurement of baseline FPA foreshortening,
      bending, and twisting associated with each posture. Markers were retrieved and 7
      different stents were deployed across the adductor hiatus in the same limbs.
      Markers were then redeployed in the stented FPAs, and limbs were reimaged.
      Baseline and stented FPA deformations were compared to determine the influence of
      each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex
      exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl
      restricted bending of the FPA. Within the stent, all devices except Viabahn
      restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted
      twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn
      restricted bending. Distal to the stents, all devices except AbsolutePro and
      Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl
      exacerbated twisting. All stents except Supera were pinched in flexed limb
      postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb
      flexion-induced FPA deformations, but in different ways. Although certain designs
      seem to accommodate some deformation modes, no device was able to match all FPA
      deformations.

PMID- 29578914
TI  - Understanding and Treating Supralevator Fistula-in-Ano: MRI Analysis of 51 Cases
      and a Review of Literature.
AB  - BACKGROUND: Supralevator fistulas are highly complex. The delineation of the
      supralevator fistula has become accurate because of MRI. OBJECTIVE: The aim of
      the study was to analyze the pathophysiology and treatment of different types of
      supralevator fistulas. DESIGN: This was a prospective study. SETTINGS: The study
      was conducted at a specialized fistula treatment center in North India. PATIENTS:
      All of the patients with fistula-in-ano who presented in the outpatient
      department were assessed with a physical examination and MRI scan. The patients
      in whom the supralevator extension was confirmed on MRI were included in the
      study. MAIN OUTCOME MEASURES: The MRI scans of patients included in the study
      were analyzed in detail to assess the types of supralevator fistulas and other
      characteristics of these fistulas. The patients who were operated on were
      followed for cure rate and deterioration in incontinence. RESULTS: Of 702
      patients with fistula-in-ano who were analyzed by MRI over a period of 3 years,
      51 patients with supralevator fistula-in-ano were identified. The mean age was
      44.3 +/- 12.1 years and the male:female ratio was 16:1. The incidence of
      supralevator fistulas was 7.26% (51 of 702). In supralevator fistulas, the
      supralevator extension (upper part) was found to be in the intersphincteric plane
      in all of the patients. This upper part could be successfully managed by laying
      it open through the transanal route. The infralevator (lower) part could be of 3
      types: intersphincteric (n = 13), low transsphincteric (n = 3), or high
      transsphincteric (n = 35). The lower part could be managed conventionally. There
      were no extrasphincteric fistulas. An extensive review of the literature revealed
      only 2 studies (total fistulas = 16) in which supralevator fistula was studied.
      LIMITATIONS: This was a retrospective study. CONCLUSIONS: The upper supralevator
      extension in all of the supralevator fistulas is almost always in the
      intersphincteric plane. This upper part could be laid open through the transanal
      route. The lower infralevator part could be of 3 types, intersphincteric, low
      transsphincteric, or high transsphincteric, which could be managed
      conventionally. Thus, supralevator fistulas could be managed successfully and
      easily. See Video Abstract at http://links.lww.com/DCR/A630.

PMID- 29578915
TI  - The Necessity and Safety of Resident Involvement in Laparoscopic Colorectal
      Surgery.

PMID- 29578917
TI  - Transanal Total Pelvic Exenteration With Sphincter-Preserving Surgery.

PMID- 29578916
TI  - A Systematic Review and Meta-analysis of Mesenchymal Stem Cell Injections for the
      Treatment of Perianal Crohn's Disease: Progress Made and Future Directions.
AB  - BACKGROUND: There has been a surge in clinical trials studying the safety and
      efficacy of mesenchymal stem cells for the treatment of perianal Crohn's disease.
      OBJECTIVE: The purpose of this work was to systematically review the literature
      to determine safety and efficacy of mesenchymal stem cells for the treatment of
      refractory perianal Crohn's disease. DATA SOURCES: Sources included PubMed,
      Cochrane Library Central Register of Controlled Trials, and Embase. STUDY
      SELECTION: Studies that reported safety and/or efficacy of mesenchymal stem cells
      for the treatment of perianal Crohn's disease were included. Two independent
      assessors reviewed eligible articles. INTERVENTION: The study intervention was
      delivery of mesenchymal stem cells to treat perianal Crohn's disease. MAIN
      OUTCOMES MEASURES: Safety and efficacy of mesenchymal stem cells used to treat
      perianal Crohn's disease were measured. RESULTS: Eleven studies met the inclusion
      criteria and were included in the systematic review. Three trials with a
      comparison arm were included in the meta-analysis. There were no significant
      increases in adverse events (OR = 1.07 (95% CI, 0.61-1.89); p = 0.81) or serious
      adverse events (OR = 0.53 (95% CI, 0.28-0.98); p = 0.04) in patients treated with
      mesenchymal stem cells. Mesenchymal stem cells were associated with improved
      healing as compared with control subjects at primary end points of 6 to 24 weeks
      (OR = 3.06 (95% CI, 1.05-8.90); p = 0.04) and 24 to 52 weeks (OR = 2.37 (95% CI,
      0.90-6.25); p = 0.08). LIMITATIONS: The study was limited by its multiple centers
      and heterogeneity in the study inclusion criteria, mesenchymal stem cell origin,
      dose and frequency of delivery, use of scaffolding, and definition and time point
      of fistula healing. CONCLUSIONS: Although there have been only 3 trials conducted
      with control arms, existing data demonstrate improved efficacy and no increase in
      adverse or serious adverse events with mesenchymal stem cells as compared with
      control subjects for the treatment of perianal Crohn's disease.

PMID- 29578918
TI  - Elective Stoma Reversal Has a Higher Incidence of Postoperative Clostridium
      Difficile Infection Compared With Elective Colectomy: An Analysis Using the
      American College of Surgeons National Surgical Quality Improvement Program and
      Targeted Colectomy Databases.
AB  - BACKGROUND: Clostridium difficile infection is caused by the proliferation of a
      gram-positive anaerobic bacteria after medical or surgical intervention and can
      result in toxic complications, emergent surgery, and death. OBJECTIVE: This
      analysis evaluates the incidence of C difficile infection in elective restoration
      of intestinal continuity compared with elective colon resection. DESIGN: This was
      a retrospective database review of the 2015 American College of Surgeons National
      Surgical Quality Improvement Project and targeted colectomy database. SETTINGS:
      The intervention cohort was defined as the primary Current Procedural Terminology
      codes for ileostomy/colostomy reversal (44227, 44620, 44625, and 44626) and
      International Classification of Diseases codes for ileostomy/colostomy status
      (VV44.2, VV44.3, VV55.2, VV55.3, Z93.2, Z93.3, Z43.3, and Z43.2). PATIENTS: A
      total of 2235 patients underwent elective stoma reversal compared with 10403
      patients who underwent elective colon resection. INTERVENTION: Multivariate
      regression modeling of the impact of stoma reversal on postoperative C difficile
      infection risk was used as the study intervention. MAIN OUTCOME MEASURES: The
      incidence of C difficile infection in the 30 days after surgery was measured.
      RESULTS: The incidence of C difficile infection in the 30-day postoperative
      period was significantly higher (3.04% vs 1.25%; p < 0.001) in patients
      undergoing stoma reversal. After controlling for differences in cohorts,
      regression analysis suggested that stoma reversal (OR = 2.701 (95% CI, 1.966
      3.711); p < 0.001), smoking (OR = 1.520 (95% CI, 1.063-2.174); p = 0.022),
      steroids (OR = 1.677 (95% CI, 1.005-2.779); p = 0.048), and disseminated cancer
      (OR = 2.312 (95% CI, 1.437-3.719); p = 0.001) were associated with C difficile
      infection incidence in the 30-day postoperative period. LIMITATIONS: The study
      was limited because it was a retrospective database review with observational
      bias. CONCLUSIONS: Patients who undergo elective stoma reversal have a higher
      incidence of postoperative C difficile infection compared with patients who
      undergo an elective colectomy. Given the impact of postoperative C difficile
      infection, a heightened sense of suspicion should be given to symptomatic
      patients after stoma reversal. See at Video Abstract at
      http://links.lww.com/DCR/A553.

PMID- 29578919
TI  - Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With
      Colorectal Cancer.
AB  - BACKGROUND: The incidence of colorectal cancer in the young (under age 40) is
      increasing, and this population has worse oncologic outcomes. Mucinous histology
      is a potential prognostic factor in colorectal cancer, but has not been evaluated
      specifically in young patients. OBJECTIVE: The objective of the study was to
      determine factors associated with poor outcome in young patients with colorectal
      cancer (<=40 years) and to determine relationships between mucinous histology and
      oncologic outcomes in this population. DESIGN: This is a retrospective study.
      SETTING: Patients from a single-institution tertiary care center were studied.
      PATIENTS: A total of 224 patients with colorectal cancer under 40 years of age
      diagnosed between 1990 and 2010 were included (mean age, 34.7 years; 51.3%
      female). 34 patients (15.2%) had mucinous histology. INTERVENTIONS(S): There were
      no interventions. MAIN OUTCOME MEASURES: Oncologic outcomes were analyzed
      according to the presence of mucinous histology. RESULTS: The mucinous and
      nonmucin colorectal cancer study populations were statistically similar in age,
      sex, tumor location, pathological stage, differentiation, and adjuvant
      chemotherapy use. Five-year disease-free survival was 29.1% versus 71.3% (p <
      0.0001) and 5-year overall survival was 54.7% versus 80.3% (p < 0.0001) for
      mucinous and nonmucinous patients, respectively. Mucinous colorectal cancers
      recurred earlier at a median time of 36.4 months versus 94.2 months for nonmucin
      colorectal cancers (p < 0.001). On multivariate analysis, pathological stage
      (stage II HR, 3.61; 95% CI, 1.37-9.50; stage III HR, 5.27; 95% CI, 2.12-12.33),
      positive margins (HR, 1.95; 95% CI, 1.12-3.23), angiolymphatic invasion (HR,
      2.15; 95% CI, 1.26-3.97), and mucinous histology (HR, 2.36; 95% CI, 1.44-3.96)
      were independently associated with worse disease-free and overall survival.
      LIMITATIONS: This is a retrospective study without genetic information.
      CONCLUSIONS: Mucinous histology is a negative prognostic factor in young patients
      with colorectal cancer. This is associated with early and high recurrence rates,
      despite use of standard neoadjuvant and adjuvant regimens. Physicians need to be
      aware of this association and potentially explore novel treatment options. See
      Video Abstract at http://links.lww.com/DCR/A575.

PMID- 29578920
TI  - Open Surgical Incisions After Colorectal Surgery Improve Quality Metrics, But Do
      Patients Benefit?
AB  - BACKGROUND: Surgical site infection is a frequent cause of morbidity after
      colorectal resection and is a quality measure for hospitals and surgeons. In an
      effort to reduce the risk of postoperative infections, many wounds are left open
      at the time of surgery for secondary or delayed primary wound closure. OBJECTIVE:
      The purpose of this study was to evaluate the impact of delayed wound closure on
      the rate of surgical infections and resource use. DESIGN: This retrospective
      propensity-matched study compared colorectal surgery patients with wounds left
      open with a cohort of patients with primary skin closure. SETTINGS: The American
      College of Surgeons National Quality Improvement Program Participant Use file for
      2014 was queried. PATIENTS: A total of 50,212 patients who underwent elective or
      emergent colectomy, proctectomy, and stoma creation were included. MAIN OUTCOME
      MEASURES: Rates of postoperative infections and discharge to medical facilities
      were measured. RESULTS: Surgical wounds were left open in 2.9% of colorectal
      cases (n = 1466). Patients with skin left open were broadly higher risk, as
      evidenced by a significantly higher median estimated probability of 30-day
      mortality (3.40% vs 0.45%; p < 0.0001). After propensity matching (n = 1382 per
      group), there were no significant differences between baseline characteristics.
      Within the matched cohort, there were no differences in the rates of 30-day
      mortality, deep or organ space infection, or sepsis (all p > 0.05). Resource use
      was higher for patients with incisions left open, including longer length of stay
      (11 vs 10 d; p = 0.006) and higher rates of discharge to a facility (34% vs 27%;
      p < 0.001). LIMITATIONS: This study was limited by its retrospective design and a
      large data set with a bias toward academic institutions. CONCLUSIONS: In a well
      matched colorectal cohort, secondary or delayed wound closure eliminates
      superficial surgical infections, but there was no decrease in deep or organ space
      infections. In addition, attention should be given to the possibility for
      increased resource use associated with open surgical incisions. See Video
      Abstract at http://links.lww.com/DCR/A560.

PMID- 29578921
TI  - Updated clinical indications for transcatheter aortic valve implantation in
      patients with severe aortic stenosis: expert opinion of the Italian Society of
      Cardiology and GISE.
AB  - : The introduction of percutaneous treatment of severe aortic stenosis with
      transcatheter aortic valve implantation (TAVI) remains one of the greatest
      achievements of interventional cardiology. In fact, TAVI emerged as a better
      option than either medical therapy or balloon aortic valvuloplasty for patients
      who cannot undergo surgical aortic valve replacement (SAVR) or are at high
      surgical risk. Recently, increased operator experience and improved device
      systems have led to a worldwide trend toward the extension of TAVI to low-risk or
      intermediate-risk patients. In this expert opinion paper, we first discuss the
      basic pathophysiology of aortic stenosis in different settings then the key
      results of recent clinical investigations on TAVI in intermediate-risk aortic
      stenosis patients are summarized. Particular emphasis is placed on the results of
      the nordic aortic valve intervention, placement of aortic transcatheter valves
      (PARTNER) 2 and Surgical Replacement and Transcatheter Aortic Valve Implantation
      Randomized trials. The PARTNER 2 was the first large randomized trial that
      evaluated the outcome of TAVI in patients at intermediate risk. The PARTNER 2
      data demonstrated that TAVI is a feasible and reasonable alternative to surgery
      in intermediate-risk patients (Society of Thoracic Surgeons 4-8%), especially if
      they are elderly or frail. There was a significant interaction between TAVI
      approach and mortality, with transfemoral TAVI showing superiority over SAVR.
      Moreover, we examine the complementary results of the recently concluded Surgical
      Replacement and Transcatheter Aortic Valve Implantation trial. This prospective
      randomized trial demonstrated that TAVI is comparable with surgery (primary end
      point 12.6% in the TAVI group vs. 14.0% in the SAVR group) in severe aortic
      stenosis patients deemed to be at intermediate risk. We review the most relevant
      clinical evidence deriving from nonrandomized studies and meta-analyses.
      Altogether, clinical outcome available data suggest that TAVI with a newer
      generation device might be the preferred treatment option in this patient
      subgroup. Finally, the differences between the latest European and American
      Guidelines on TAVI were reported and discussed. The conclusion of this expert
      opinion article is that TAVI, if feasible, is the treatment of choice in patients
      with prohibitive or high surgical risk and may lead to similar or lower early and
      midterm mortality rates compared with SAVR in intermediate-risk patients with
      severe aortic stenosis.

PMID- 29578922
TI  - Old methods of myocardial revascularization to treat refractory angina.

PMID- 29578924
TI  - Sickle Cell Disease is Associated With Elevated Levels of Skin Advanced Glycation
      Endproducts.
AB  - Sickle cell disease (SCD) is associated with increased oxidative stress which
      potentially enhances generation of advanced glycation endproducts (AGEs). We
      estimated skin accumulation of AGEs in SCD patients and assessed their
      relationship with hemolysis and nephropathy. Skin intrinsic fluorescence (SIF),
      an estimate of AGEs, was assessed in African American patients with and without
      SCD. After skin excitation with light at 375, 405, and 420 nm, raw
      autofluorescence was adjusted using specific intrinsic corrections. Group
      differences in SIF were evaluated by multiple variable regression using
      chronological age and sex as covariates. The relationship of SIF with
      reticulocyte count, serum lactate dehydrogenase, estimated glomerular filtration
      rate (GFR), plasma creatinine, bilirubin, and urine microalbumin was assessed.
      There were 48 SCD patients (29 male/19 female, age=13.4+/-3.6 y) and 51 controls
      (25 male/26 female, age=10.4+/-5.0 y). SIF375(1.0,0.0), SIF405(0.5,0.5), and
      SIF420(0.5,0.5) were significantly higher in SCD patients. There was no
      difference in SIF between SCD patients with and without microalbuminuria. SIF
      420(0.5,0.5) was correlated with reticulocyte count (r=0.33; P=0.03). Skin AGEs
      as estimated by SIF were higher in children with SCD and weakly associated with 1
      measure of hemolysis. Further study is needed to determine whether chronic
      increased deposition of AGEs is associated with development of complications of
      SCD.

PMID- 29578925
TI  - Successful Management of a Rare Cause of Hemolytic Uremic Syndrome With
      Eculizumab in a Child.
AB  - BACKGROUND: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic
      hemolytic anemia, acute renal failure, and thrombocytopenia. It very rarely
      coexists with acute lymphoblastic leukemia (ALL) emerging before, simultaneously,
      or after the diagnosis has been made, and management of the patient may be
      difficult. CASE: We present the case of a 7-year-old boy who was diagnosed with
      HUS and initially managed by hemodialysis (HD). Thereafter, HUS progressed, and
      neurological findings developed. The patient was treated with eculizumab,
      agressive blood pressure control, and antiepileptic drugs. At the fifth month of
      follow-up, the patient was diagnosed with acute B-cell lymphoblastic leukemia
      with fever, bone pain, hepatosplenomegaly, and pancytopenia. After initiation of
      ALL treatment, he had no episodes of HUS, despite cessation of eculizumab.
      CONCLUSION: In conclusion, eculizumab may be a treatment of choice to prevent
      further systemic damage in recurrent HUS episodes of patients with borderline
      changes in the bone marrow until ALL is constantly diagnosed.

PMID- 29578926
TI  - Altered white matter microstructure associated with mild and moderate depressive
      symptoms in young adults, a diffusion tensor imaging study.
AB  - In the context of growing evidence supporting disturbed neural connectivity in
      the pathogenesis of depressive symptoms, we used the diffusion tensor imaging
      technique to investigate white matter disruptions in previously undiagnosed and
      hence treatment-naive young adults with mild and moderate depressive symptoms
      screened by Beck's Depression Inventory test compared with age-matched and sex
      matched healthy controls. This is the first diffusion tensor imaging study to
      assess minor forms of depression. We hypothesized that subthreshold depressive
      symptoms share the same neural disruptions as major depressive disorder (MDD).
      Each group included 47 participants with a mean age of 20.1+/-1.1 years. The
      exploratory region of interest method was used to assess integrity (fractional
      anisotropy and mean diffusivity) in 48 regions of the brain based on Mori atlas.
      Data were recruited from the Southwest University Longitudinal Imaging Multimodal
      Brain Data Repository. The following pathways showed significant microstructural
      changes by means of reduced fractional anisotropy in the group with depressive
      symptoms compared with normal participants: pontine crossing tract; genu of the
      corpus callosum; posterior limb of the internal capsule (bilaterally); and
      anterior, posterior, and superior corona radiata (bilaterally). None of the above
      regions, but the middle cerebellar peduncle and the right superior fronto
      occipital fasciculus were shown to differ significantly in the mean diffusivity
      values between the two groups. On the basis of the current results, our findings
      provide evidence that the white matter impairments in the interhemispheric
      connections and frontal-subcortical neural circuits may play a key role in the
      pathogenesis of depression in young adults. The similarity of neural
      underpinnings in MDD and minor depressive disorder in this study further proves
      that these two mood disorders exist in a continuum, and milder depressive
      symptoms can herald a major episode. Besides the high prevalence and great burden
      of subthreshold forms of depression on personal and social aspects of life, there
      is lack of knowledge of them and most studies have mainly focused on MDD. This
      study provides a new avenue in addressing neuropathology of depression, mainly in
      subtle forms that are almost always overlooked.

PMID- 29578927
TI  - Minimal starting time of data reconstruction for qualitative myocardial perfusion
      rubidium-82 positron emission tomography imaging.
AB  - OBJECTIVE: Qualitative positron emission tomography (PET) myocardial perfusion
      imaging (MPI) scans are reconstructed with a delay after an injection of rubidium
      82 (Rb) to ensure blood pool clearance and sufficient left ventricle to
      myocardium contrast. Our aim was to derive the minimal starting time of data
      reconstruction (STDR) after an injection of Rb for which the diagnostic value and
      image quality remained unaffected. MATERIALS AND METHODS: We retrospectively
      included 23 patients who underwent rest-stress Rb PET MPI using 740 MBq. Patients
      fulfilling one of the two criteria indicating a slow blood pool clearance
      (ejection fraction <50% and/or cardiac output <3 l/min) were included in a
      consecutive manner. PET images using five different STDRs (1:15-2:15 min) were
      reconstructed and compared with reference images (STDR of 2:30 min). Differences
      in the summed rest score greater than or equal to 3 and total perfusion deficit
      greater than 3% were considered to significantly influence the diagnostic value.
      In addition, image quality was scored by two experts as not interpretable,
      inferior, adequate, or excellent. RESULTS: The summed rest score differed greater
      than or equal to 3 from the reference in seven or more patients (>=30%) using
      STDR less than or equal to 2:00 min (P<0.02). STDR less than or equal to 1:30 min
      resulted in six or more patients (>=26%) with a total perfusion deficit
      difference greater than 3% (P<0.03).In addition, STDR less than or equal to 2:00
      min resulted in a lower image quality (P<0.002) and STDR less than or equal to
      2:15 min resulted in greater than or equal to two scans with noninterpretable
      image quality. CONCLUSION: STDR less than or equal to 2:15 min resulted in lower
      diagnostic value or insufficient image quality for qualitative PET MPI using 740
      MBq Rb. An STDR of 2:30 min can be considered for clinical adoption.

PMID- 29578928
TI  - Negative correlation of high-density of lipoprotein-cholesterol and bone mineral
      density in postmenopausal Iranian women with vitamin D deficiency.
AB  - OBJECTIVE: The aim of the study was to investigate the association between high
      density lipoprotein (HDL) and bone status taking into account serum vitamin D
      levels in postmenopausal Iranian women. METHODS: During January 2015 and February
      2016, a total of 488 postmenopausal Iranian women participated in this cross
      sectional study, all of whom were not taking osteoporosis medication and were not
      suffering from any chronic disorder. Dual X-ray absorptiometry was used to assess
      bone mineral density (BMD) of the total hip, femoral neck, and lumbar vertebrae
      (L2-L4). Each person was categorized based on the World Health Organization
      osteoporosis criteria in at least one skeletal region. At the end of the data
      collection, lipid profiles and vitamin D levels were measured for all
      participants. Vitamin D serum levels less than 30 ng/mL were defined as vitamin D
      deficiency or insufficiency. RESULTS: 27.9% of all participants displayed
      osteoporosis. Osteoporotic participants tended to be older with higher HDL serum
      levels (P < 0.001). No significant difference was seen in low-density of
      lipoprotein, total triglyceride, and total cholesterol levels among participants
      (P > 0.05). In a univariate model, after adjusting for age, menopausal age,
      obesity, physical activity, and use of antihyperlipidemic drugs (statins), there
      were significant negative associations among HDL levels and BMD values and T
      score in the three regions (P < 0.004). Interestingly, after classification of
      participants based on vitamin D levels and adjustment for confounding factors,
      these significant negative associations between HDL levels and BMD values as well
      as T-score were observed only in participants with vitamin D deficiency or
      insufficiency, in the three regions (P < 0.008). CONCLUSIONS: Our data show that
      in postmenopausal women with vitamin D deficiency, serum levels of HDL have
      negative correlation with bone status.

PMID- 29578929
TI  - The Factors Affecting Teaching and Learning Professionalism Among Medical
      Teachers.
AB  - Given the special importance of medical professionalism, a successful faculty
      development strategy not only teaches professionalism in cognitive domain but
      also creates practical instructors who can act as role models for students. This
      study proposed to identify themes that can explain effective factors in teaching
      and learning professionalism among medical teachers. The study was qualitative.
      Twenty-four experts in medical education participated in the study from all
      medical universities of Iran. Data gathering was performed via semistructured
      interviews. Interviews were transcribed and analyzed by classic content analysis.
      At the end, the factors were confirmed by the focus group consisting of six
      experts. One hundred seventy-seven codes were extracted. Codes were categorized
      into 24 subcategories and five main categories: (1) culture, (2) educational
      factors, (3) background, (4) attitude, and (5) organizational factors. There are
      many effective factors for a proper faculty development in teaching and learning
      professionalism. These factors could be individualized, organizational, or
      external. We cannot design a program without considering these factors.

PMID- 29578930
TI  - Interpersonal Conflict and Organizational Commitment Among Licensed Practical
      Nurses.
AB  - The shortage of nursing professionals in the United States is unquestionable.
      This shortage, which is predicted to continue into the foreseeable future, is a
      particularly salient problem within the nursing profession. This is especially
      true for long-term care facility administrators who not only are faced with the
      challenge of increasing numbers of aging residents but also regularly struggle
      with turnover among more cost-effective nursing staff, such as licensed practical
      nurses (LPNs). The primary purpose of this study was to examine whether perceived
      interpersonal conflict influences organizational commitment among LPNs. To
      accomplish this, we analyzed responses from 1165 LPNs throughout a Midwestern
      state who were queried on their perceptions of interpersonal conflict and
      organizational commitment in their work settings. Considering a wide range of
      potential confounding influences such as age and years working as an LPN, for
      example, we found that higher perceived interpersonal conflict was associated
      with significantly lower levels of organizational commitment. The implications of
      these findings, along with recommendations for nurse administrators to reduce LPN
      turnover, are discussed in the article.

PMID- 29578931
TI  - Contributors to Operating Room Underutilization and Implications for Hospital
      Administrators.
AB  - Operating rooms (ORs) are an important source of hospital revenue, and
      utilization rate is a key determinant of OR efficiency. Multiple factors
      contribute to OR underutilization, and OR managers may have biased views about
      which factors contribute most to OR underutilization. We examined various factors
      leading to OR underutilization at one academic tertriary care center.Data were
      collected retrospectively from over a 12-month period. Contribution to OR
      underutilization was measured in terms of hours of OR underutilization.
      Statistical significance between categories and days was calculated using an
      unpaired t test.By comparing means of the various contributors to OR
      underutilization (patient in the room, turnover time, scheduling gaps, OR holds,
      closed rooms), we determined that mid/end-of-day gaps and closed rooms
      contributed the most hours (9.7% and 4.6%, respectively; P < .0001) to OR
      underutilization, whereas turnover time and "patient in the room" contributed the
      least (2.0% and 0.8%, respectively; P < .0001).The contributors to OR
      underutilization are complex, and many OR staff from physicians to nurses and OR
      administrators may have biased views about which factors contribute most
      predominantly to inefficiency. Awareness of how various factors contribute to OR
      underutilization can pave the way for goal-directed changes on a systems-based
      level to improve efficiency in the OR by decreasing underutilization.

PMID- 29578933
TI  - Complex iatrogenic clubfoot: is it a real entity?
AB  - In our study, we aimed to demonstrate whether a complex iatrogenic clubfoot
      really exists; identify the causative mechanisms; and determine the outcome if
      properly treated. We observed 54 clubfeet previously treated unsuccessfully by
      manipulation and casting elsewhere. All the feet had been classified at diagnosis
      as typical clubfeet. In 26 cases, the cast had slipped down, entrapping the foot
      in a plantar-flexed position. Nine clubfeet out of those 26 cases presented the
      clinical features of a complex iatrogenic deformity. These were treated with the
      modified Ponseti protocol and evaluated at follow-up according to the
      International Clubfoot Study Group Score. The length of follow-up averaged 7.2
      years. Two feet showed an excellent result, five feet showed a good result, and
      two feet showed a fair result. The relapse rate was 55% in complex clubfeet.
      Relapsed clubfeet were treated by Achilles tenotomy or lengthening and anterior
      tibial tendon transfer. We believe that faulty manipulation and a poor casting
      technique may convert a typical clubfoot into a complex iatrogenic deformity.
      Risk factors include severe clubfoot, short and stubby foot, and unmolded casts
      slipping down.

PMID- 29578934
TI  - Universal versus selective ultrasound screening for developmental dysplasia of
      the hip: a single-centre retrospective cohort study.
AB  - A total of 28 068 infants were studied to investigate whether universal
      ultrasound screening for developmental dysplasia of the hip results in fewer
      delayed presentations than selective screening, and whether the screening
      protocol affects subsequent treatment. The rate of delayed presentation was not
      lower with selective screening compared with universal screening but all cases of
      delayed presentation in this cohort were administrative errors. There were no
      sonographic errors (false-negatives). The treatment rate was significantly higher
      with universal screening but infants were treated earlier and were significantly
      less likely to require any surgical intervention. Those requiring surgery were
      less likely to require open reduction or pelvic osteotomy.

PMID- 29578932
TI  - Carotid Artery Stiffness and Cognitive Decline Among Women With or at Risk for
      HIV Infection.
AB  - BACKGROUND: Vascular stiffness is associated with aging and cognitive impairment
      in older populations without HIV. HIV has been linked to increased vascular
      stiffness. We examined whether vascular stiffness relates to cognitive decline at
      younger ages in women with or at risk for HIV. METHODS: We evaluated the
      association of carotid artery stiffness with decline in neuropsychological test
      performance among participants in the Women's Interagency HIV Study and assessed
      whether HIV modified the association. Baseline carotid stiffness, defined by the
      distensibility index, was determined at a single visit using carotid artery
      ultrasound. Longitudinal neuropsychological testing from 2004-2016 included Trail
      Making Tests A and B and the Symbol Digit Modalities Test. Relationships were
      assessed with linear mixed-effect models adjusted for demographic, behavioral,
      cardiometabolic, and neuropsychological factors. RESULTS: Among 1662 women (1192
      [72%] HIV+), median baseline age was 41 years (interquartile range 34-47), with
      60% non-Hispanic black and 28% Hispanic. Lower baseline distensibility (greater
      carotid stiffness) was associated with greater decline in neuropsychological test
      scores over 10-year follow-up as measured by Symbol Digit Modalities Test
      (adjusted beta = -0.06 per SD, P < 0.001), Trail Making Test A (beta = -0.08 per
      SD; P < 0.001), and Trail Making Test B (beta = -0.08 per SD; P < 0.001). Changes
      in cognitive function did not differ by HIV serostatus, or HIV-related factors.
      CONCLUSIONS: Higher carotid stiffness was independently associated with faster
      decline in executive functioning, information processing, and psychomotor speed
      even in mostly middle-aged minority women and regardless of HIV serostatus. Our
      study highlights the need for cardiovascular risk factor modification to prevent
      premature cognitive deterioration in this at-risk population.

PMID- 29578935
TI  - PENETRATING OCULAR INJURY WITH RETAINED INTRAOCULAR FOREIGN BODY FROM DRYWALL.
AB  - PURPOSE: To present a case of open globe injury and retained intraocular foreign
      body secondary to drywall. METHODS: Interventional case report. RESULTS: A 21
      year-old man presented with corneal laceration, iris defect, and vitreous
      hemorrhage after hammering drywall. Computed tomography scan was negative for
      intraocular foreign body, but a drywall intraretinal foreign body was found on 25
      gauge vitrectomy. Intraoperative findings and 6-month follow-up are presented.
      CONCLUSION: Intraocular foreign body must always be suspected in all cases of
      penetrating ocular trauma. Although magnetic resonance imaging is ideal in
      diagnosing nonmetallic foreign bodies, computed tomography scan with Hounsfield
      units should be used in an emergency setting.

PMID- 29578936
TI  - Mathematical Representation of Standard Kt/V Including Ultrafiltration and
      Residual Renal Function.
AB  - A new formula for calculating standard Kt/V from clinical data has been derived
      mathematically. It is based on using the relation between eKt/V and the pre- and
      postdialysis concentrations in order to find the steady state concentrations. The
      resulting expression for standard Kt/V depends on the treatment schedule (number,
      length, and spacing of treatments), residual renal function, and eKt/V and
      relative ultrafiltration volume of each individual treatment. These results
      include the effects of ultrafiltration and residual renal function also in the
      case with unequal treatments that may be arbitrarily distributed over the week.
      The new formula is found to agree, within small fractions of a percentage, with
      standard Kt/V from simulations of 3 and 5 days per week schedules. Several
      approximations are also suggested and their accuracies analyzed. It is shown that
      the use of the midweek eKt/V and ultrafiltration for all treatments of the week
      is an acceptable approximation. In the presence of residual renal function, the
      timing of the treatments is an important factor, and particularly in this case,
      the new formula shows improved accuracy over previously published formulas.

PMID- 29578937
TI  - Determination of Tacrolimus Concentration and Protein Expression of P
      Glycoprotein in Single Human Renal Core Biopsies.
AB  - BACKGROUND: Tacrolimus (TAC) is currently the cornerstone of immunosuppressive
      protocols for renal transplant recipients. Despite therapeutic whole blood
      monitoring, TAC is associated with nephrotoxicity, and it has been hypothesized
      that intrarenal accumulation of TAC and/or its metabolites are involved. As TAC
      is a substrate of P-glycoprotein (P-gp), the expression and activity of this
      efflux transporter could influence the levels of TAC in renal tissue. The primary
      aim of this study was to develop and validate a method for quantification of TAC
      in tissue homogenates from single human renal core biopsies. The secondary aim
      was to provide measures of P-gp expression and of the demethylated metabolites of
      TAC in the same renal biopsy. METHODS: Human renal tissue, with and without
      clinical TAC exposure, was used for method development and validation.
      Homogenates were prepared with bead-beating, and concentrations of TAC and its
      demethylated metabolites were analyzed with liquid chromatography tandem mass
      spectrometry after protein precipitation. A Western blot method was used for
      semiquantification of P-gp expression in the homogenates. The final methods were
      applied to renal core biopsies from 2 transplant patients. RESULTS: The TAC assay
      showed within- and between-run mean accuracy between 99.7% and 107% and
      coefficients of variation <=6.7%. Matrix effects were nonsignificant, and samples
      were stable for 3 months preanalytically when stored at -80 degrees C. TAC
      concentrations in the renal core biopsies were 62.6 and 43.7 pg/mg tissue. The
      methods for measurement of desmethyl-TAC and P-gp expression were suitable for
      semiquantification in homogenates from renal core biopsies. CONCLUSIONS: These
      methods may be valuable for the elucidation of the pharmacokinetic mechanisms
      behind TAC-induced nephrotoxicity in renal transplant recipients.

PMID- 29578938
TI  - Quantification of Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in Human Serum
      by UHPLC-MS/MS-Method Development, Validation, and Application.
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) are prescribed for anticoagulation
      in patients with atrial fibrillation and venous thromboembolic disease. Fixed
      doses are recommended, but measuring their serum drug concentrations as a basis
      for dose adjustments may be useful in some clinical settings. METHODS: An ultra
      high-performance liquid chromatography-tandem mass spectrometry method for the
      analysis of the DOACs apixaban, dabigatran, edoxaban, and rivaroxaban in human
      serum was developed and validated. A 100-uL serum sample was handled using a
      pipetting robot. Protein precipitation was performed with 375 uL of 1% formic
      acid in acetonitrile (vol/vol), and phospholipid removal was performed using a
      Waters Ostro 96-well plate. The injection volume was 1 uL, and run time was 3.0
      minutes. RESULTS: The calibration range was 5-800 nmol/L. The between-day
      precision relative SDs were in the range of 3.3%-10%. Recoveries ranged from 85%
      to 105%, and matrix effects from 88% to 102%, when corrected with internal
      standard. Edoxaban was, in contrast to the other DOACs, unstable when stored for
      more than 6 hours at 30 degrees C. The suitability of the method was demonstrated
      by analyzing routine samples from 345 patients undergoing anticoagulation
      treatment. CONCLUSIONS: The developed method fulfilled the set validation
      criteria, and its suitability was demonstrated in a routine setting. The
      instability of edoxaban may complicate the transport of routine samples to the
      laboratory.

PMID- 29578939
TI  - Diminished Dynamic Physical Performance Is Associated With Orthostatic
      Hypotension in Geriatric Outpatients.
AB  - BACKGROUND AND PURPOSE: Orthostatic hypotension (OH), a blood pressure drop after
      postural change, is a highly prevalent and disabling syndrome in older adults.
      Yet, the association between physical performance and OH is not clearly
      established. The aim of this study was to determine whether different types of
      physical performance are associated with OH in a clinically relevant population
      of geriatric outpatients. METHODS: This cross-sectional study included 280
      geriatric outpatients (mean age: 82.2 years, standard deviation: 7.1).
      Orthostatic hypotension was determined using intermittently measured blood
      pressure and continuously measured blood pressure in a random subgroup of 58
      patients. Physical performance was classified into a dynamic type (4-m Walk Test,
      Chair Stand Test, and Timed Up and Go test) and a static type (standing balance
      tests, handgrip strength). Associations were analyzed using logistic regression
      models with adjustments for age, sex, weight, and height. RESULTS: Diminished
      physical performance on the Chair Stand Test was associated with OH measured
      intermittently. Diminished physical performance on all dynamic physical domains
      (4-m Walk Test, Chair Stand Test, and Timed Up and Go test) was associated with
      OH measured continuously. Static physical performance was not significantly
      associated with OH. CONCLUSION: Dynamic physical performance tests with a
      substantial postural change and center of mass displacement were significantly
      associated with OH. The influence of physical performance on OH in daily routine
      activities should be further explored to establish counteracting interventions.

PMID- 29578940
TI  - RELATIONSHIP OF CLINICAL FEATURES AND BASELINE TUMOR SIZE WITH GENE EXPRESSION
      PROFILE STATUS IN UVEAL MELANOMA: A Multi-institutional Study.
AB  - PURPOSE: To study the relationship between gene expression profile subclass and
      clinical features in a multicenter cohort of patients with uveal melanoma.
      METHODS: A retrospective, multicenter study was undertaken with patients entered
      from nine major ocular oncology centers from across the United States. Eligible
      patients had uveal melanoma and underwent I-125 plaque brachytherapy with
      concurrent tumor biopsy with gene expression profile testing between January 1,
      2010, and October 28, 2014. Data were collected regarding patient demographics,
      baseline tumor clinical features, and gene expression profile results.
      Statistical analyses were performed using the Fisher's exact test, Wilcoxon rank
      sum test, Kruskal-Wallis test, and proportional-odds cumulative logit modeling.
      RESULTS: Inclusion criteria were met for 379 patients. Gene expression profile
      class divided the cohort into two main groups, Class 1 (n = 263) and Class 2 (n =
      113). Class 1 tumors were further subdivided into Class 1a (n = 186) and Class 1b
      (n = 77). The differences between Class 1 and Class 2 tumors were similar to
      previous studies, except the finding of Class 2 tumors being more likely to have
      associated exudative retinal detachment (P < 0.001). There was no statistically
      significant difference between Class 1 and Class 2 tumors based on the presence
      of lipofuscin, drusen, or subretinal fluid. Class 1a tumor patients, compared
      with Class 1b, were significantly older (P = 0.034). Class 2 tumors, when
      compared with Class 1b, were associated with increasing patient age (P < 0.001),
      larger tumor height (P = 0.010), ciliary body involvement (P = 0.001), exudative
      retinal detachment (P = 0.024), and anterior tumor location (P < 0.001). When the
      tumors were grouped into Collaborative Ocular Melanoma Study size categories,
      increasing tumor size category was significantly associated with Class 2 status:
      6% of small tumors, 32% of medium tumors, and 53% of large tumors were Class 2.
      CONCLUSION: In a multi-institutional setting, we found that the only significant
      difference in clinical features between Class 1a and Class 1b tumors was that
      patients with Class 1a tumors were older at the time of diagnosis. We also found
      that Class 1a and Class 1b have clinical features distinct from Class 2 tumors.
      The distribution of the gene expression profile subclasses among the size groups
      was similar to reported time-to-metastasis data among the same size groupings.
      Our clinical findings support the current molecular classification-based survival
      data previously reported in uveal melanoma.

PMID- 29578941
TI  - Reply.

PMID- 29578944
TI  - Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled,
      double-blind clinical study in subjects with painful diabetic peripheral
      neuropathy.
AB  - The effect of PF-05089771, a selective, peripherally restricted Nav1.7 sodium
      channel blocker on pain due to diabetic peripheral neuropathy was investigated in
      a randomised, placebo and active-controlled parallel group clinical trial
      (NCT02215252). A 1-week placebo-run in the period was followed by a 4-week
      treatment period and a 1-week placebo run-out/taper-down period. Single-blind
      placebo was administered throughout run-in and run-out periods. Subjects were
      randomised to receive either PF-05089771 150 mg twice daily, pregabalin 150 mg
      twice daily, or placebo during the 4-week treatment period. One hundred thirty
      five subjects were randomised. The primary endpoint was the average pain score
      derived from subjects' Numerical Rating Scale scores over the past 7 days of week
      4 of the double-blind treatment period. Predefined efficacy criteria for the
      trial were the effect of PF-05089771 being >0.5 units better than placebo at
      interim analysis after completion of the first part of the study. Although a
      trend for a reduction in the weekly average pain score in the PF-05089771
      treatment group was observed, this was not statistically significant when
      compared with placebo at week 4, with a mean posterior difference of -0.41 (90%
      credible interval: -1.00 to 0.17). The effect of PF-05089771 was smaller than
      that seen with pregabalin, which was statistically significant when compared with
      placebo at week 4, with a mean posterior difference of -0.53 (90% credible
      interval: -0.91 to -0.20). As predefined efficacy criteria were not met, the
      study did not proceed to the second part. PF-05089771 was well tolerated.
      Possible reasons for the modest efficacy observed with PF-05089771 are discussed.

PMID- 29578943
TI  - Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits.
AB  - Wind-up is a frequency-dependent increase in the response of spinal cord neurons,
      which is believed to underlie temporal summation of nociceptive input. However,
      whether spinoparabrachial neurons, which likely contribute to the affective
      component of pain, undergo wind-up was unknown. Here, we addressed this question
      and investigated the underlying neural circuit. We show that one-fifth of lamina
      I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in
      these cells is mediated in part by a network of spinal excitatory interneurons
      that show reverberating activity. These findings provide insight into a
      polysynaptic circuit of sensory augmentation that may contribute to the wind-up
      of pain's unpleasantness.

PMID- 29578945
TI  - Mechanical perturbation model of temporomandibular joint disorders and assessment
      of musculature.

PMID- 29578946
TI  - Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle
      cell disease.
AB  - Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by
      chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises
      induced pain can be chronic or episodic. Because analgesics typically used to
      treat pain are not very effective in SCD, opioids, including morphine, are a
      primary treatment for managing pain in SCD but are associated with many serious
      side effects, including constipation, tolerance, addiction, and respiratory
      depression. Thus, there is a need for the development of novel treatments for
      pain in SCD. In this study, we used the Townes transgenic mouse model of SCD to
      investigate the antinociceptive efficacy of the bivalent ligand, MCC22, and
      compared its effectiveness with morphine. MCC22 consists of a mu-opioid receptor
      agonist and a chemokine receptor-5 (CCR5) antagonist that are linked through a 22
      atom spacer. Our results show that intraperitoneal administration of MCC22
      produced exceptionally potent dose-dependent antihyperalgesia as compared to
      morphine, dramatically decreased evoked responses of nociceptive dorsal horn
      neurons, and decreased expression of proinflammatory cytokines in the spinal
      cord. Moreover, tolerance did not develop to its analgesic effects after repeated
      administration. In view of the extraordinary potency of MCC22 without tolerance,
      MCC22 and similar compounds may vastly improve the management of pain associated
      with SCD.

PMID- 29578948
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.
AB  - Peripheral neuropathic pain associated with partial nerve injury is believed to
      be driven partly by aberrant spontaneous activity (SA) in both injured and
      uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are
      not fully understood, but hyperpolarization-activated cyclic nucleotide-gated
      (HCN) channels which underlie the excitatory Ih current have been implicated in
      SA generation in axotomized A-fiber neurons after L5-spinal nerve
      ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which
      involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with
      neuroinflammation-inducing chromic gut, we examined whether HCN channels also
      contribute to SA in the adjacent L4-neurons. Intracellular recordings from L4-DRG
      neurons in control rats, and L4-DRG neurons in mSNA rats were made using in vivo
      voltage- and current-clamp techniques. Compared with control, L4 C-nociceptors
      and Abeta-low-threshold mechanoreceptors (LTMs) exhibited SA 7 days after mSNA.
      This was accompanied, in C-nociceptors, by a significant increase in Ih
      amplitude, the percentage of Ih-expressing neurons, and Ih activation rate.
      Hyperpolarization-activated cyclic nucleotide-gated channel blockade with ZD7288
      (10 mg/kg, intravenously) suppressed SA in C-nociceptors, but not Abeta-LTMs, and
      caused in C-nociceptors, membrane hyperpolarization and a decrease in Ih
      activation rate. Furthermore, intraplantar injection of ZD7288 (100 MUM) was
      found to be as effective as gabapentin (positive control) in attenuating cold
      hypersensitivity in mSNA rats. These findings suggest that HCN channels
      contribute to nerve injury-induced SA in L4 C-nociceptors, but not Abeta-LTMs,
      and that ZD7288 exerts its analgesic effects by altering Ih activation properties
      and/or causing membrane hyperpolarization in L4 C-nociceptors.

PMID- 29578947
TI  - Chronic pain impairs cognitive flexibility and engages novel learning strategies
      in rats.
AB  - Cognitive flexibility, the ability to adapt behavior to changing outcomes, is
      critical to survival. The prefrontal cortex is a key site of cognitive control,
      and chronic pain is known to lead to significant morphological changes to this
      brain region. Nevertheless, the effects of chronic pain on cognitive flexibility
      and learning remain uncertain. We used an instrumental paradigm to assess
      adaptive learning in an experimental model of chronic pain induced by tight
      ligation of the spinal nerves L5/6 (spinal nerve ligation model). Naive, sham
      operated, and spinal nerve ligation (SNL) rats were trained to perform fixed
      ratio, variable-ratio, and contingency-shift behaviors for food reward. Although
      all groups learned an initial lever-reward contingency, learning was slower in
      SNL animals in a subsequent choice task that reversed reinforcement
      contingencies. Temporal analysis of lever-press responses across sessions
      indicated no apparent deficits in memory consolidation or retrieval. However,
      analysis of learning within sessions revealed that the lever presses of SNL
      animals occurred in bursts, followed by delays. Unexpectedly, the degree of
      bursting correlated positively with learning. Under a variable-ratio
      probabilistic task, SNL rats chose a less profitable behavioral strategy compared
      with naive and sham-operated animals. After extinction of behavior for learned
      preferences, SNL animals reverted to their initially preferred (ie, less
      profitable) behavioral choice. Our data suggest that in the face of uncertainty,
      chronic pain drives a preference for familiar associations, consistent with
      reduced cognitive flexibility. The observed burst-like responding may represent a
      novel learning strategy in animals with chronic pain.

PMID- 29578949
TI  - How condition-specific do measures of pain intensity need to be?

PMID- 29578951
TI  - Validation of the Combined Comorbidity Index of Charlson and Elixhauser to
      Predict 30-Day Mortality Across ICD-9 and ICD-10.
AB  - OBJECTIVES: To validate and compare performance of an International
      Classification of Diseases, tenth revision (ICD-10) version of a combined
      comorbidity index merging conditions of Charlson and Elixhauser measures against
      individual measures in the prediction of 30-day mortality. To select a weight
      derivation method providing optimal performance across ICD-9 and ICD-10 coding
      systems. RESEARCH DESIGN: Using 2 adult population-based cohorts of patients with
      hospital admissions in ICD-9 (2005, n=337,367) and ICD-10 (2011, n=348,820), we
      validated a combined comorbidity index by predicting 30-day mortality with
      logistic regression. To appreciate performance of the Combined index and both
      individual measures, factors impacting indices performance such as population
      characteristics and weight derivation methods were accounted for. We applied 3
      scoring methods (Van Walraven, Schneeweiss, and Charlson) and determined which
      provides best predictive values. RESULTS: Combined index [c-statistics: 0.853
      (95% confidence interval: CI, 0.848-0.856)] performed better than original
      Charlson [0.841 (95% CI, 0.835-0.844)] or Elixhauser [0.841 (95% CI, 0.837
      0.844)] measures on ICD-10 cohort. All weight derivation methods provided close
      high discrimination results for the Combined index (Van Walraven: 0.852,
      Schneeweiss: 0.851, Charlson: 0.849). Results were consistent across both coding
      systems. CONCLUSIONS: The Combined index remains valid with both ICD-9 and ICD-10
      coding systems and the 3 weight derivation methods evaluated provided consistent
      high performance across those coding systems.

PMID- 29578952
TI  - Failure-to-Rescue After Acute Myocardial Infarction.
AB  - BACKGROUND: Failure-to-rescue (FTR), originally developed to study quality of
      care in surgery, measures an institution's ability to prevent death after a
      patient becomes complicated. OBJECTIVES: Develop an FTR metric modified to
      analyze acute myocardial infarction (AMI) outcomes. RESEARCH DESIGN: Split-sample
      design: a random 20% of hospitals to develop FTR definitions, a second 20% to
      validate test characteristics, and an out-of-sample 60% to validate results.
      SUBJECTS: Older Medicare beneficiaries admitted to short-term acute-care
      hospitals for AMI between 2009 and 2011. MEASURES: Thirty-day mortality and FTR
      rates, and in-hospital complication rates. RESULTS: The 60% out-of-sample
      validation included 234,277 patients across 1142 hospitals that admitted at least
      50 patients over 2.5 years. In total, 72.1% of patients were defined as Medically
      Complicated (complex on admission or subsequently developed a complication or
      died without a recorded complication) of whom 19.3% died. Spearman r between
      hospital risk-adjusted 30-day mortality and FTR was 0.89 (P<0.0001); Mortality
      versus Complication=-0.01 (P=0.6198); FTR versus Complication=-0.10 (P=0.0011).
      Major teaching hospitals displayed 19% lower odds of FTR versus non-teaching
      hospitals (odds ratio=0.81, P<0.0001), while hospitals as a group defined by
      teaching hospital status, comprehensive cardiac technology, and having good
      nursing mix and staffing, displayed a 33% lower odds of FTR (odds ratio=0.67,
      P<0.0001) versus hospitals without any of these characteristics. CONCLUSIONS: A
      modified FTR metric can be created that has many of the advantageous properties
      of surgical FTR and can aid in studying the quality of care of AMI admissions.

PMID- 29578953
TI  - Care Coordination and Multispecialty Teams in the Care of Colorectal Cancer
      Patients.
AB  - OBJECTIVES: To estimate the association between provider and team experience and
      adherence to guidelines, survival, and utilization among colorectal cancer
      patients in North Carolina. SUBJECTS: The analysis cohort included 7295 patients
      diagnosed with incident stage II/III colorectal cancer between 2004 and 2013 who
      received surgery. METHODS: Primary outcomes included adherence to guidelines:
      consultation with a medical oncologist (stage III), receipt of adjuvant
      chemotherapy (stage III), and receipt of surveillance colonoscopy posttreatment.
      Secondary outcomes included 5-year overall survival, number of surveillance
      radiology studies, any unplanned hospitalization, and any emergency department
      visit. The primary predictors were measures of provider volume and patient
      sharing across surgeons and medical oncologists. Regression analyses adjusted for
      patient and provider characteristics. RESULTS: Patients whose surgeons shared
      >40% of their colorectal cancer patients in the previous year with a medical
      oncologist were (1) more likely to have had a consultation with a medical
      oncologist [marginal effect (ME)=13.3 percentage points, P-value<0.001], (2) less
      likely to receive a surveillance colonoscopy within 12 months (ME=3.5 percentage
      points, P-value=0.049), and (3) received more radiology studies (ME=0.254
      studies, P-value=0.029). Patients whose surgeon and medical oncologist shared
      >20% of their colorectal cancer patients with each other in the previous year had
      a higher likelihood of receiving adjuvant chemotherapy (ME=11.5 percentage
      points, P-value<0.001) and surveillance colonoscopy within 12 months (ME=6.7
      percentage points, P-value=0.030) and within 18 months (ME=6.2 percentage points,
      P-value=0.054). CONCLUSIONS: Our study shows that team experience is associated
      with patients' quality of care, survival, and utilization.

PMID- 29578954
TI  - Health Care Costs and Utilization of Dabigatran Compared With Warfarin for
      Secondary Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation: A
      Retrospective Population Study.
AB  - BACKGROUND: It remains unclear whether the use of new oral anticoagulants,
      compared with warfarin, is economically beneficial in Asian countries. OBJECTIVE:
      The objective of this study is to compare the health care costs and utilization
      between dabigatran and warfarin in a real-world nonvalvular atrial fibrillation
      (NVAF) population. RESEARCH DESIGN: Data were obtained from the Taiwan National
      Health Insurance Database, and patients with an NVAF diagnosis between June 1,
      2012, and May 31, 2014, were identified using the International Classification of
      Diseases, Ninth Revision code of 427.31. The patients in the dabigatran cohort
      were matched 1:2 to those in the warfarin cohort by sex, age, residential region,
      and a propensity score that incorporated a major bleeding history, CHADS2 score,
      and Charlson Comorbidity Index. The all-cause health care utilization and
      associated costs of the 2 treatment groups were compared at 3 and 12 months.
      RESULTS: A total of 1149 patients taking dabigatran were identified and matched
      with 2298 warfarin users. During the 3-month observation period, the likelihood
      of having at least 1 hospitalization among dabigatran users was significantly
      lower than that of warfarin users (odds ratio=0.78; P=0.001). Patients in the
      dabigatran group incurred lower mean emergency department costs ($2383.1 vs.
      $3033.6), mean ischemic stroke-related hospitalization costs ($8869.5 vs.
      $13,990.5), and mean all-cause hospitalization costs ($32,402.2 vs. $50,669.9) at
      3 months. However, both the mean and median outpatient costs of warfarin users
      were consistently lower than those of dabigatran users ($17,161.2 vs. $24,931.4
      and $10,509.0 vs. $20,671.5, respectively). Similar trends were observed at 12
      months, except that the 2 groups had comparable total health care costs.
      CONCLUSIONS: The use of dabigatran is associated with lower emergency department
      and all-cause hospitalization costs but greater outpatient costs in a real-world,
      NVAF patient population compared with warfarin.

PMID- 29578956
TI  - Mineralocorticoid receptor antagonists: time of repositioning them in the
      treatment of arterial hypertension.

PMID- 29578955
TI  - Oregon Medicaid Expenditures After the 2014 Affordable Care Act Medicaid
      Expansion: Over-time Differences Among New, Returning, and Continuously Insured
      Enrollees.
AB  - BACKGROUND: There is interest in assessing health care utilization and
      expenditures among new Medicaid enrollees after the 2014 Medicaid expansion.
      Recent studies have not differentiated between newly enrolled individuals and
      those returning after coverage gaps. OBJECTIVES: To assess health care
      expenditures among Medicaid enrollees in the 24 months after Oregon's 2014
      Medicaid expansions and examine whether expenditure patterns were different among
      the newly, returning, and continuously insured (CI). RESEARCH DESIGN:
      Retrospective cohort study using inverse-propensity weights to adjust for
      differences between groups. SUBJECTS: Oregon adult Medicaid beneficiaries insured
      continuously from 2014 to 2015 who were either newly, returning, or CI. MEASURES:
      Monthly expenditures for inpatient care, prescription drugs, total outpatient
      care, and subdivisions of outpatient care: emergency department, dental, mental
      and behavioral health, primary care, and specialist care. RESULTS: After initial
      increases, newly and returning insured (RI) outpatient expenditures dropped below
      CI. Expenditures for emergency department and dental services among the RI
      remained higher than among the newly insured. Newly insured mental and behavioral
      health, primary care, and specialist expenditures plateaued higher than RI.
      Prescription drug expenditures increased over time for all groups, with CI
      highest and RI lowest. All groups had similar inpatient expenditures over 24
      months post-Medicaid expansion. CONCLUSIONS: Our findings reveal that outpatient
      expenditures for new nonpregnant, non-dual-eligible Oregon Medicaid recipients
      stabilized over time after meeting pent-up demand, and prior insurance history
      affected the mix of services that individuals received. Policy evaluations should
      consider expenditures over at least 24 months and should account for enrollees'
      prior insurance histories.

PMID- 29578957
TI  - Blood pressure variability and kidney disease: another vicious circle?

PMID- 29578958
TI  - Parental target organ damage and risk of target organ damage in offspring.

PMID- 29578959
TI  - Fibrates in hypertension: where do we stand?

PMID- 29578960
TI  - Does increase in arterial stiffness and wave reflection precede development of
      placental-mediated complications in pregnancy?

PMID- 29578961
TI  - Sirtuin 1 as a potential therapeutic target in pulmonary artery hypertension.

PMID- 29578962
TI  - Albuminuria and diabetes: a question of eye and skin points of view.

PMID- 29578963
TI  - Orthostatic hypotension, focus on cognitive pattern.

PMID- 29578965
TI  - Characteristics associated with lower blood pressure when using a sit-stand desk.

PMID- 29578964
TI  - Comparison between invasive and noninvasive techniques of evaluation of
      microvascular structural alterations.
AB  - BACKGROUND: The evaluation of the morphological characteristics of small
      resistance arteries in humans is challenging. The gold standard method is
      generally considered to be the measurement by wire or pressure micromyography of
      the media-to-lumen ratio of subcutaneous small vessels obtained by local
      biopsies. However, noninvasive techniques for the evaluation of retinal
      arterioles were recently proposed; in particular, two approaches, scanning laser
      Doppler flowmetry (SLDF) and adaptive optics, seem to provide useful information;
      both of them provide an estimation of the wall-to-lumen ratio (WLR) of retinal
      arterioles. Moreover, a noninvasive measurement of basal and total capillary
      density may be obtained by videomicroscopy/capillaroscopy. No direct comparison
      of these three noninvasive techniques in the same population was previously
      performed; in particular, adaptive optics was never validated against
      micromyography. METHODS: In the current study, we enrolled 41 controls and
      patients: 12 normotensive lean controls, 12 essential hypertensive lean patients,
      nine normotensive obese patients and eight hypertensive obese patients undergoing
      elective surgery. All patients underwent a biopsy of subcutaneous fat during
      surgery. Subcutaneous small resistance artery structure was assessed by wire
      micromyography and the media-to-lumen ratio was calculated. WLR of retinal
      arterioles was obtained by SLDF and adaptive optics. Functional (basal) and
      structural (total) microvascular density was evaluated by capillaroscopy before
      and after venous congestion. RESULTS AND CONCLUSION: Our data suggest that
      adaptive optics has a substantial advantage over SLDF in terms of evaluation of
      microvascular morphology, as WLR measured with adaptive optics is more closely
      correlated with the M/L of subcutaneous small arteries (r = 0.84, P < 0.001 vs. r
      = 0.52, P < 0.05, slopes of the relations: P < 0.01 adaptive optics vs. SLDF). In
      addition, the reproducibility of the evaluation of the WLR with adaptive optics
      is far better, as compared with SLDF, as intraobserver and interobserver
      variation coefficients are clearly smaller. This may be important in terms of
      clinical evaluation of microvascular morphology in a clinical setting, as
      micromyography has substantial limitations in its clinical application due to the
      local invasiveness of the procedure.

PMID- 29578966
TI  - In Reply.

PMID- 29578967
TI  - Early Second-Trimester Fetal Growth Restriction and Adverse Perinatal Outcomes.

PMID- 29578968
TI  - In Reply.

PMID- 29578969
TI  - Ovarian Vein Thrombosis: Incidence of Recurrent Venous Thromboembolism and
      Survival.

PMID- 29578970
TI  - In Reply.

PMID- 29578972
TI  - In Reply.

PMID- 29578971
TI  - Epidural Analgesia During the Second Stage of Labor: A Randomized Controlled
      Trial.

PMID- 29578973
TI  - Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict
      Preterm Delivery in Symptomatic Women.

PMID- 29578974
TI  - In Reply.

PMID- 29578975
TI  - Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture:
      A Randomized Controlled Trial.

PMID- 29578977
TI  - Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture:
      A Randomized Controlled Trial: Correction.

PMID- 29578976
TI  - In Reply.

PMID- 29578978
TI  - What Do Medical Students Interested in Obstetrics and Gynecology Value in Their
      Future Careers? [28I]: Correction.

PMID- 29578979
TI  - Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict
      Preterm Delivery in Symptomatic Women: Correction.

PMID- 29578982
TI  - ACOG Publications.

PMID- 29578983
TI  - ACOG Committee Opinion No. 732 Summary: Influenza Vaccination During Pregnancy.
AB  - Influenza vaccination is an essential element of prepregnancy, prenatal, and
      postpartum care because influenza can result in serious illness, including a
      higher chance of progressing to pneumonia, when it occurs during the antepartum
      or postpartum period. In addition to hospitalization, pregnant women with
      influenza are at increased risk of intensive care unit admission and adverse
      perinatal and neonatal outcomes. The Centers for Disease Control and Prevention's
      Advisory Committee on Immunization Practices and the American College of
      Obstetricians and Gynecologists recommend that all adults receive an annual
      influenza vaccine and that women who are or will be pregnant during influenza
      season receive an inactivated influenza vaccine as soon as it is available. In
      the United States, the influenza season typically occurs from October to May.
      Ideally, an influenza vaccination should be given before the end of October, but
      vaccination throughout the influenza season is encouraged to ensure protection
      during the period of circulation. Any of the licensed, recommended, age
      appropriate, inactivated influenza vaccines can be given safely during any
      trimester. Therefore, it is critically important that obstetrician-gynecologists
      and other obstetric care providers recommend and advocate for the influenza
      vaccine. Obstetrician-gynecologists are encouraged to stock and administer the
      influenza vaccine to their pregnant patients in their offices, and should get the
      influenza vaccine themselves every season. If the influenza vaccine cannot be
      offered in a practice, obstetrician-gynecologists and obstetric care providers
      should refer patients to another health care provider, pharmacy, or community
      vaccination center. This updated Committee Opinion includes more recent data on
      the safety and efficacy of influenza vaccination during pregnancy and
      recommendations for treatment and postexposure chemoprophylaxis.

PMID- 29578984
TI  - ACOG Committee Opinion No. 733 Summary: Employment Considerations During
      Pregnancy and the Postpartum Period.
AB  - In the United States, it is common for women, including mothers and pregnant
      women, to work outside the home. Working during pregnancy is generally safe. For
      those in high-risk occupations or with medically complicated pregnancies, work
      accommodations often can allow for continued safe employment. The major
      employment issues concerning pregnant women include pregnancy-related
      discrimination, work accommodations that allow continued employment, job
      protected leave, and wage replacement while on leave. Workplace discrimination
      related to being pregnant and pregnancy-related harassment, including
      discrimination in the hiring process, is prohibited by federal and state law.
      There is no federal law guaranteeing comprehensive accommodations for pregnant
      and postpartum workers. Current federal and state laws provide protection for
      some pregnant women, but not others, because of eligibility requirements and
      state-by-state differences. By writing appropriate notes to employers,
      obstetrician-gynecologists and other obstetric care providers can be instrumental
      in obtaining accommodations for their patients who are able to continue working.
      Accommodations that allow a woman to keep working are the most reliable way to
      guarantee pay, benefits, and job protection. Obstetrician-gynecologists and other
      obstetric care providers also can assist pregnant women and their partners by
      providing them with information and resources that might help them better
      understand their employment rights. However, in cases for which potential job
      discrimination has occurred, accommodations are denied, extended medical leave is
      necessary, or when other complex employment questions arise, legal assistance
      should be obtained.

PMID- 29578985
TI  - ACOG Committee Opinion No. 732: Influenza Vaccination During Pregnancy.
AB  - Influenza vaccination is an essential element of prepregnancy, prenatal, and
      postpartum care because influenza can result in serious illness, including a
      higher chance of progressing to pneumonia, when it occurs during the antepartum
      or postpartum period. In addition to hospitalization, pregnant women with
      influenza are at increased risk of intensive care unit admission and adverse
      perinatal and neonatal outcomes. The Centers for Disease Control and Prevention's
      Advisory Committee on Immunization Practices and the American College of
      Obstetricians and Gynecologists recommend that all adults receive an annual
      influenza vaccine and that women who are or will be pregnant during influenza
      season receive an inactivated influenza vaccine as soon as it is available. In
      the United States, the influenza season typically occurs from October to May.
      Ideally, an influenza vaccination should be given before the end of October, but
      vaccination throughout the influenza season is encouraged to ensure protection
      during the period of circulation. Any of the licensed, recommended, age
      appropriate, inactivated influenza vaccines can be given safely during any
      trimester. Therefore, it is critically important that obstetrician-gynecologists
      and other obstetric care providers recommend and advocate for the influenza
      vaccine. Obstetrician-gynecologists are encouraged to stock and administer the
      influenza vaccine to their pregnant patients in their offices, and should get the
      influenza vaccine themselves every season. If the influenza vaccine cannot be
      offered in a practice, obstetrician-gynecologists and obstetric care providers
      should refer patients to another health care provider, pharmacy, or community
      vaccination center. This updated Committee Opinion includes more recent data on
      the safety and efficacy of influenza vaccination during pregnancy and
      recommendations for treatment and postexposure chemoprophylaxis.

PMID- 29578986
TI  - ACOG Committee Opinion No. 733: Employment Considerations During Pregnancy and
      the Postpartum Period.
AB  - In the United States, it is common for women, including mothers and pregnant
      women, to work outside the home. Working during pregnancy is generally safe. For
      those in high-risk occupations or with medically complicated pregnancies, work
      accommodations often can allow for continued safe employment. The major
      employment issues concerning pregnant women include pregnancy-related
      discrimination, work accommodations that allow continued employment, job
      protected leave, and wage replacement while on leave. Workplace discrimination
      related to being pregnant and pregnancy-related harassment, including
      discrimination in the hiring process, is prohibited by federal and state law.
      There is no federal law guaranteeing comprehensive accommodations for pregnant
      and postpartum workers. Current federal and state laws provide protection for
      some pregnant women, but not others, because of eligibility requirements and
      state-by-state differences. By writing appropriate notes to employers,
      obstetrician-gynecologists and other obstetric care providers can be instrumental
      in obtaining accommodations for their patients who are able to continue working.
      Accommodations that allow a woman to keep working are the most reliable way to
      guarantee pay, benefits, and job protection. Obstetrician-gynecologists and other
      obstetric care providers also can assist pregnant women and their partners by
      providing them with information and resources that might help them better
      understand their employment rights. However, in cases for which potential job
      discrimination has occurred, accommodations are denied, extended medical leave is
      necessary, or when other complex employment questions arise, legal assistance
      should be obtained.

PMID- 29578987
TI  - Beyond the real world: attention debates in auditory mismatch negativity.
AB  - The aim of this study was to address the potential for the auditory mismatch
      negativity (aMMN) to be used in applied event-related potential (ERP) studies by
      determining whether the aMMN would be an attention-dependent ERP component and
      could be differently modulated across visual tasks or virtual reality (VR)
      stimuli with different visual properties and visual complexity levels. A total of
      80 participants, aged 19-36 years, were assigned to either a reading-task (21 men
      and 19 women) or a VR-task (22 men and 18 women) group. Two visual-task groups of
      healthy young adults were matched in age, sex, and handedness. All participants
      were instructed to focus only on the given visual tasks and ignore auditory
      change detection. While participants in the reading-task group read text slides,
      those in the VR-task group viewed three 360 degrees  VR videos in a random order
      and rated how visually complex the given virtual environment was immediately
      after each VR video ended. Inconsistent with the finding of a partial significant
      difference in perceived visual complexity in terms of brightness of virtual
      environments, both visual properties of distance and brightness showed no
      significant differences in the modulation of aMMN amplitudes. A further analysis
      was carried out to compare elicited aMMN amplitudes of a typical MMN task and an
      applied VR task. No significant difference in the aMMN amplitudes was found
      across the two groups who completed visual tasks with different visual-task
      demands. In conclusion, the aMMN is a reliable ERP marker of preattentive
      cognitive processing for auditory deviance detection.

PMID- 29578988
TI  - Diversity.

PMID- 29578989
TI  - Our Journal Unites Us: Global Responsibilities and Possibilities for Pediatric
      Physical Therapy.
AB  - PURPOSE: This article was designed to describe personal and social
      responsibilities for strengthening the science of pediatric physical therapy and
      effective international research collaboration and communication. KEY POINTS:
      Common flaws in research design and analysis are reviewed with recommendations
      for developing research students' design and analytical skills. Our social
      responsibility to be informed by global knowledge is highlighted. Barriers to
      scientific collaboration and communication including international disparities in
      scientific development and language barriers are presented. Suggestions to reduce
      these barriers are outlined. The importance of free access to scientific
      literature in developing countries is reviewed. CONCLUSION: The journal should
      assume a leadership role in building a strong science of pediatric physical
      therapy through encouraging personal and social responsibility in research and
      serving as a model of international collaboration and communication. CLINICAL
      RELEVANCE: Treatment for children with movement disorders will be improved by
      stronger science, international collaboration, and communication.

PMID- 29578990
TI  - Effects of Postural Management on Hip Migration in Children With Cerebral Palsy:
      A Systematic Review.
AB  - PURPOSE: To review the existing literature on the effects of postural management
      on hip migration in children with cerebral palsy. METHODS: A systematic
      literature search was performed using 5 databases. Quality of articles was
      assessed and study designs were appraised according to the American Academy of
      Cerebral Palsy and Developmental Medicine Systematic Review Method. RESULTS:
      Eight of 655 identified studies were included, reporting postural management in
      children with cerebral palsy. Seven of 8 studies reported positive effects on hip
      migration after postural management interventions. However, level of evidence and
      quality of the articles were low. CONCLUSION: The evidence for postural
      management to prevent or reduce hip migration in children with cerebral palsy is
      limited by the lack of high-quality studies. Strong recommendations for clinical
      practice are not possible. Future high-quality research is crucial to improve our
      understanding of the effects of postural management to prevent hip migration in
      children with cerebral palsy.

PMID- 29578991
TI  - Commentary on "Effects of Postural Management on Hip Migration in Children With
      Cerebral Palsy: A Systematic Review".

PMID- 29578992
TI  - Hand-Arm Bimanual Intensive Therapy Improves Prefrontal Cortex Activation in
      Children With Hemiplegic Cerebral Palsy.
AB  - PURPOSE: To determine the changes in the prefrontal cortical (PFC) activation
      following hand-arm bimanual intensive therapy (HABIT) in children with hemiplegic
      cerebral palsy (HCP). METHODS: Nine children with HCP and 15 children who were
      developing typically participated in the study. Children with HCP received 50
      hours of HABIT. We assessed pre- and post-HABIT PFC activation using functional
      near-infrared spectroscopy neuroimaging. Bimanual coordination and motor task
      performance were assessed using the Assisting Hand Assessment (AHA), the average
      number of shapes matched, the shape matching errors, the reaction time, the 9
      hole peg test, and the box and blocks test. RESULTS: The PFC activation decreased
      following HABIT and became similar to what was seen in the children who were
      developing typically. Post-HABIT PFC activation improvements paralleled with the
      improvements seen in the AHA and the behavioral outcomes. CONCLUSION: HABIT
      potentially improves the PFC's involvement in the action planning of the upper
      extremity movements in children with HCP.

PMID- 29578993
TI  - Commentary on "Hand-Arm Bimanual Intensive Therapy Improves Prefrontal Cortex
      Activation in Children With Hemiplegic Cerebral Palsy".

PMID- 29578994
TI  - Clubfoot Does Not Impair Gross Motor Development in 5-Year-Olds.
AB  - PURPOSE: To evaluate the gross motor development of 5-year-olds using the Peabody
      Developmental Motor Scales, 2nd Edition (PDMS-2), test after initial nonoperative
      management of clubfoot as infants. METHODS: The PDMS-2 Stationary, Locomotion,
      and Object Manipulation subtests were assessed on 128 children with idiopathic
      clubfeet at the age of 5 years. Children were categorized by their initial
      clubfoot severity as greater than 13, unilateral or bilateral involvement, and
      required surgery. RESULTS: Children with treated clubfeet had average gross motor
      scores (99 Gross Motor Quotient) compared with age-matched normative scores.
      Children with more severe clubfeet required surgery significantly more than
      children with less severe scores (P < .01). Peabody scores were not significantly
      different according to initial clubfoot severity, unilateral versus bilateral
      involvement, and surgical versus nonsurgical outcomes. CONCLUSIONS: Clubfoot does
      not significantly impair gross motor development in 5-year-olds.

PMID- 29578995
TI  - Commentary on "Clubfoot Does Not Impair Gross Motor Development in 5-Year-Olds".

PMID- 29578996
TI  - Role of Pediatric Physical Therapists in Promoting Sports Participation in
      Developmental Coordination Disorder.
AB  - PURPOSE: To explore the role of pediatric physical therapists (PPT) in promoting
      sports participation in children with developmental coordination disorder (DCD)
      and identify associated barriers and facilitators. METHODS: Questionnaires were
      provided to 243 PPTs. Qualitative, semistructured, in-depth interviews were
      administered with the PPTs, children with DCD, and parents. RESULTS:
      Approximately 67% of questionnaires were returned. Approximately 46% of PPTs were
      active in guiding children with DCD to sports clubs. This guidance was
      facilitated by knowledge of local sports, clubs that include children with DCD,
      and contact persons. Barriers to sports participation were the motor impairment
      or coincident disorder, insufficient participants to compose a team, and lack of
      guidance on how to include children with DCD. CONCLUSIONS: PPTs currently guide
      children with DCD to sports clubs, but this guidance may be improved by
      connecting them to special exercise programs and mainstream sports clubs and
      examining children's experiences during sports.

PMID- 29578997
TI  - Commentary on "Role of Pediatric Physical Therapists in Promoting Sports
      Participation in Developmental Coordination Disorder".

PMID- 29578998
TI  - Commentary on "Linking the Pediatric Evaluation of Disability Inventory-Computer
      Adaptive Test (PEDI-CAT) to the International Classification of Function".

PMID- 29578999
TI  - Commentary on "Short-Term Recovery of Balance Control: Association With
      Chemotherapy-Induced Peripheral Neuropathy in Pediatric Oncology".

PMID- 29579000
TI  - Use of a Midliner Positioning System for Prevention of Dolichocephaly in Preterm
      Infants.
AB  - PURPOSE: The purpose of this study was to determine effectiveness of a midliner
      positioning system (MPS, Tortle Midliner) for preventing dolichocephaly. METHODS:
      This was a nonrandomized, prospective study of 30 premature infants (study
      cohort, SC) using an MPS compared with a retrospective study cohort (RSC) of 65
      infants who received standard of care intervention. RESULTS: RSC baseline cranial
      index (CI) of 80% and final CI of 77% significantly decreased over an average 5.5
      weeks (P < .0001). The SC baseline CI and the final CI were both 79% over an
      average 5.7 weeks, indicating no significant difference between CI measures (P =
      .6). Gestational age, birth weight, reflux, time on continuous positive airway
      pressure, and time in a supine position were not associated with dolichocephaly.
      CONCLUSIONS: The SC developed less cranial molding (ie, had greater CI), compared
      with the RSC. A larger randomized study is needed to recommend routine use of MPS
      for prevention and/or treatment of cranial molding in premature infants.

PMID- 29579001
TI  - Commentary on "Use of a Midliner Positioning System for Prevention of
      Dolichocephaly in Preterm Infants".

PMID- 29579002
TI  - Descriptive Report of the Impact of Fatigue and Current Management Strategies in
      Cerebral Palsy.
AB  - PURPOSE: To describe the effect of fatigue and self-management practices for
      adolescents and young adults with cerebral palsy. METHODS: A survey of 124 people
      with cerebral palsy with the Fatigue Impact and Severity Self-Assessment.
      RESULTS: Participants in Gross Motor Function Classification System (GMFCS) level
      I experienced little effect of fatigue, with high proportions of this group
      disagreeing to statements about fatigue impacting their general activities,
      mobility, and social activities. Participants in GMFCS levels II to V reported
      effect of fatigue on activities. Differences between groups were evident in
      questions related to fatigue interference with length of time for physical
      activity and with motivations to participate in social activities. All other
      items related to management of fatigue were not significantly different between
      groups. CONCLUSIONS: Fatigue effect is greater for participants with more
      functional limitations. The lack of significant differences between groups, on
      the Management and Activity Modification subscale, indicates more research is
      needed regarding strategies for fatigue management.

PMID- 29579003
TI  - Commentary on "Descriptive Report of the Impact of Fatigue and Current Management
      Strategies in Cerebral Palsy".

PMID- 29579004
TI  - Head Control Changes After Headpod Use in Children With Poor Head Control: A
      Feasibility Study.
AB  - PURPOSE: To determine the feasibility of Headpod use to improve head control in
      children with cerebral palsy classified as Gross Motor Function Classification
      System level V. METHODS: Children (3-11 years) with poor head control were video
      recorded before and after 3 and 6 months of Headpod use. Head control without
      Headpod was measured by active time children could hold head upright and number
      of head bobs in 5 minutes. RESULTS: Fourteen children enrolled with 43% attrition
      rate. While average active time increased, average head bobs decreased and there
      were significant improvements in active time, but not head bobs. Active times
      were higher at 6 months compared with 3 months and baseline. Surveyed parents
      reported that the changes were apparent, supporting the large quantitative
      treatment effect. CONCLUSIONS: Six months of Headpod use, 45 minutes per day,
      appears to be feasible, has a large effect on active head control, and merits a
      larger randomized controlled trial.

PMID- 29579005
TI  - A Pediatric Service-Learning Program in Physical Therapy Education.
AB  - PURPOSE: The purpose of this report was to describe a pediatric service-learning
      program in entry-level physical therapy (PT) education in Taiwan. KEY POINTS: To
      meet the needs of the local community and provide preclinical service-learning
      experience to PT students with people with physical disability, a service
      learning program of a 2-day camp for children with cerebral palsy (CP) was
      developed in 2012. To date, 356 entry-level PT students have participated in this
      program, serving 286 children and their families. Important professional
      attributes, identified by the World Confederation for Physical Therapy guideline,
      such as altruism, compassion and caring, cultural competence, personal and
      professional development, professional duty, social responsibility and advocacy,
      and teamwork, were in the reflective reports of some of the PT students.
      CONCLUSIONS: The experiences provided by this pediatric PT service-learning
      program appear to have the potential to foster the development of professional
      attributes in entry-level PT students.

PMID- 29579006
TI  - Epidemiology of Cerebral Palsy in Northeastern Switzerland.
AB  - PURPOSE: Cerebral palsy (CP) is the most common motor disability of childhood.
      Less is known about its prevalence and associated factors in Switzerland, so we
      aimed to fill this knowledge gap in one Swiss canton, evaluating the feasibility
      to build up a CP registry. METHODS: A retrospective review of medical records was
      undertaken. Children born during 1995 and 2009 in the canton of Saint Gallen
      diagnosed with CP were eligible for inclusion. RESULTS: A total of 140 patients
      formed the study cohort. The prevalence of CP was 0.19%, with 85% of children
      affected by spastic CP. CONCLUSIONS: The results of the present study were
      comparable with data of the Surveillance of Cerebral Palsy in Europe network.
      Moreover, this pilot study demonstrated the feasibility and usefulness of
      creating a registry of children affected by CP.

PMID- 29579008
TI  - Functional Mobility Improved After Intensive Progressive Resistance Exercise in
      an Adolescent With Spina Bifida.
AB  - PURPOSE: To describe the use and effectiveness of a novel intensive progressive
      resistance exercise (PRE) approach to address the functional goals of a 14-year
      old adolescent with a myelomeningocele. SUMMARY OF KEY POINTS: The child had
      lower extremity weakness, knee and hip flexion contractures, impaired
      somatosensation, and cardiopulmonary deconditioning, affecting gait mechanics and
      functional ambulation. An 8-week intensive PRE-based intervention was designed to
      improve walking in the home by targeting both power-generating and stabilizing
      lower extremity musculature. Secondary intervention focused on cardiopulmonary
      endurance training. CONCLUSIONS: The child demonstrated improvements in gait
      speed, walking endurance, and functional lower extremity strength. Knee
      contracture was moderately responsive to sustained stretching and positioning.
      WHAT THIS CASE ADDS TO EVIDENCE-BASED PRACTICE: This intensive PRE training
      approach had been effective for improving function among youth with cerebral
      palsy, and to our knowledge it had not yet been applied to youth with other
      neurological conditions.

PMID- 29579009
TI  - Targeted Training in Managing Children With Poor Trunk Control: 4 Case Reports.
AB  - PURPOSE: This study investigated whether targeted training was feasible with
      young children younger than 2 years with poor trunk control due to cerebral palsy
      or developmental delay without using specialized equipment and the overall change
      in trunk control and functional ability, with the addition of targeted training
      to standard care physical therapy. SUMMARY OF KEY POINTS: Four children younger
      than 24 months with motor disorders were recruited. No difficulty was identified
      in using targeted training with this group. Within 3 months of commencing
      intervention, the 4 children had increased trunk control and functional abilities
      including independent sitting and bilateral hand use in play. CONCLUSIONS AND
      RECOMMENDATIONS FOR CLINICAL PRACTICE: This form of targeted training was
      feasible for young children with motor disorders and augmented standard care
      therapy in enhancing both trunk control and motor skills. Targeted training
      should be further investigated as a potentially effective treatment.

PMID- 29579011
TI  - Histologic and Outcome Study Supports Reclassifying Appendiceal Goblet Cell
      Carcinoids as Goblet Cell Adenocarcinomas, and Grading and Staging Similarly to
      Colonic Adenocarcinomas.
AB  - Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior
      ranges from indolent to highly aggressive, depending on tumor grade. Current
      grading systems for these tumors are based on identifying an adenocarcinoma
      arising in the setting of a goblet cell carcinoid tumor, which distinguishes this
      tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell
      tumors are predominantly tumors of mucin secreting cells, we propose that they be
      classified as goblet cell adenocarcinomas, and graded using a methodology that
      has parallels in colorectal adenocarcinoma grading. We graded a large series of
      goblet cell adenocarcinomas by assessing the proportion of the tumor that
      demonstrates tubular or clustered growth. Histologic grade correlated with
      overall survival independent of stage, with median overall survival of 204, 86,
      and 29 months for low-grade, intermediate-grade, and high-grade goblet cell
      adenocarcinomas, respectively. Tumor stage also correlated with overall survival.
      We also graded the tumors according to previously proposed grading systems, and
      found that these systems are valid, in that they segregate patients according to
      prognosis.

PMID- 29579010
TI  - Intraoperative Consultation and Macroscopic Handling: The International Society
      of Urological Pathology (ISUP) Testicular Cancer Consultation Conference
      Recommendations.
AB  - The International Society of Urological Pathology held a conference on issues in
      testicular and penile pathology in Boston in March 2015, which included a
      presentation by the testis macroscopic features working group. The presentation
      focused on current published guidance for macroscopic handling of testicular
      tumors and retroperitoneal lymph node dissections with a summary of results from
      an online survey of members preceding the conference. The survey results were
      used to initiate discussions, but decisions on practice were made by expert
      consensus rather than voting. The importance of comprehensive assessment at the
      time of gross dissection with confirmation of findings by microscopic assessment
      was underscored. For example, the anatomic landmarks denoting the distinction of
      hilar soft tissue invasion (pT2) from spermatic cord invasion (pT3 category) can
      only be determined by careful macroscopic assessment in many cases. Other
      recommendations were to routinely sample epididymis, rete testis, hilar soft
      tissue, and tunica vaginalis in order to confirm macroscopic invasion of these
      structures or if not macroscopically evident, to exclude subtle microscopic
      invasion. Tumors 2 cm or less in greatest dimension should be completely
      embedded. If the tumor is >2 cm in greatest dimension, 10 blocks or a minimum of
      1 to 2 additional blocks per centimeter should be taken (whichever is greater).

PMID- 29579012
TI  - The Influence of Concordant Complex Posture and Loading Rate on Motion Segment
      Failure: A Mechanical and Microstructural Investigation.
AB  - STUDY DESIGN: Microstructural investigation of compression-induced herniation of
      a lumbar disc held in a concordant complex posture. OBJECTIVE: To explore the
      significance of loading rate in a highly asymmetric concordant posture, comparing
      the mechanisms of failure to an earlier study using a nonconcordant complex
      posture. SUMMARY OF BACKGROUND DATA: A recent study with a nonconcordant complex
      posture (turning in the opposite direction to that which the load is applied)
      demonstrated the vulnerability of the disc to loading that is borne by one set of
      oblique-counter oblique fiber sets in the alternating lamellae of the annulus,
      and aggravated by an elevated loading rate. Given the strain rate-dependent
      properties of the disc it might be expected that the outcome differs if the
      posture is reversed. METHODS: Forty-one motion segments from ovine 16 spines were
      split into two cohorts; adopting the previously employed low rate (40 mm/min) and
      surprise rate (400 mm/min) of loading. Both groups of damaged discs were then
      analyzed microstructurally. RESULTS: With the lower rate loading the concordant
      posture significantly reduced the load required to cause disc failure than
      earlier described for nonconcordant posture (6.9 vs. 8.4 kN), with more direct
      tears and alternate lamella damage extending to the anterior disc. Contrary to
      this result, with a surprise rate, the load at failure was significantly
      increased with the concordant posture (8.08 vs. 6.96 kN), although remaining
      significantly less than that from a simple flexed posture (9.6 kN). Analysis of
      the damage modes and postures suggest facet engagement plays a significant role.
      CONCLUSION: This study confirms that adding shear to the posture lowers the load
      at failure, and causes alternate lamella rupture. Load at failure in a complex
      posture is not determined by loading rate alone. Rather, the strain rate
      dependent properties of the disc influence which elements of the system are
      brought into play. LEVEL OF EVIDENCE: N/A.

PMID- 29579013
TI  - The Impact of Comorbid Mental Health Disorders on Complications Following
      Cervical Spine Surgery With Minimum 2-Year Surveillance.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To improve understanding of the
      impact of comorbid mental health disorders (MHDs) on long-term outcomes following
      cervical spinal fusion in cervical radiculopathy (CR) or cervical myelopathy (CM)
      patients. SUMMARY OF BACKGROUND DATA: Subsets of patients with CR and CM have
      MHDs, and their impact on surgical complications is poorly understood. METHODS:
      Patients admitted from 2009 to 2013 with CR or CM diagnoses who underwent
      cervical surgery with minimum 2-year surveillance were retrospectively reviewed
      using New York State's Statewide Planning and Research Cooperative System.
      Patients with a comorbid MHD were compared against those without (no-MHD).
      Univariate analysis compared demographics, complications, readmissions, and
      revisions between MHD and no-MHD cohorts. Multivariate binary logistic regression
      models identified independent predictors of outcomes (covariates: age, sex,
      Charlson/Deyo score, and surgical approach). RESULTS: A total of 20,342 patients
      (MHD: n = 4819; no-MHD: n = 15,523) were included. MHDs identified: depressive
      (57.8%), anxiety (28.1%), sleep (25.2%), and stress (2.9%). CR patients had
      greater prevalence of comorbid MHD than CM patients (P = 0.015). Two years
      postoperatively, all patients with MHD had significantly higher rates of
      complications (specifically: device-related, infection), readmission for any
      indication, and revision surgery (all P < 0.05); regression modeling corroborated
      these findings and revealed combined surgical approach as the strongest predictor
      for any complication (CR, odds ratio [OR]: 3.945, P < 0.001; CM, OR: 2.828, P <
      0.001) and MHD as the strongest predictor for future revision (CR, OR: 1.269, P =
      0.001; CM, OR: 1.248, P = 0.008) in both CR and CM cohorts. CONCLUSION: Nearly
      25% of patients admitted for CR and CM carried comorbid MHD and experienced
      greater rates of any complication, readmission, or revision, at minimum, 2 years
      after cervical spine surgery. Results must be confirmed with retrospective
      studies utilizing larger national databases and with prospective cohort studies.
      Patient counseling and psychological screening/support are recommended to
      complement surgical treatment. LEVEL OF EVIDENCE: 3.

PMID- 29579014
TI  - A Physical Test to Estimate Suitable Workloads for an Exercise Program in Breast
      Cancer Survivors.
AB  - Epidemiologic studies suggest that patients with breast cancer who gain weight
      after diagnosis have a higher risk of recurrence and death. Regular physical
      exercise can help minimize post-diagnosis weight gain. The objective of the study
      was to assess the effectiveness of a physical test for individualizing the
      workloads used during a fitness program.To continuously individualize the
      intensity of the training, a test was designed and integrated into the sessions.
      The test consisted in monitoring heart rate and workload during two bouts of
      cycling at moderate intensity. The workload parameters recorded during the tests
      were later used as reference values to plan the intensity of the next inperson
      training sessions.The five tests carried out during the twelve weeks of the
      intervention showed significant differences in intensity (F=3.034, p=0.047).
      Compared to the first evaluation, the intensities measured during the third,
      fourth and fifth tests presented increases of 9.9% (p=0.02), 13.2% (p=0.019) and
      17.5% (p=0.002) respectively. A significant increase in workload with respect to
      body weight was observed in the physical assessment performed after the program
      (t= 13.2, p=0.0001). The peak oxygen consumption with respect to body weight
      (peak VO2) achieved by the participants during the assessment at the end of the
      program had also increased (t= 9.72, P= 0.0001).The intensity test, introduced in
      the training sessions along with the physical exercise program, was an easy-to
      use, practical tool for monitoring intensity. It allows an adjustment of the
      workload over the program period that respects the individual progression of each
      patient.

PMID- 29579015
TI  - The aVOR App Increases Medical Students' Competence in Treating Benign Paroxysmal
      Positional Vertigo (BPPV).
AB  - HYPOTHESIS: Implementation of the "aVOR app" into teaching courses at medical
      school enhances students' satisfaction with the course and increases their
      competence in treating benign paroxysmal positional vertigo (BPPV). BACKGROUND:
      BPPV is often underdiagnosed and left untreated. One problem in teaching the
      management of BPPV to health care professionals is the lack of simulation-based
      training tools. The aVOR app (aVOR = angular vestibulo-ocular reflex) works as a
      bionic labyrinth that simulates the activation of the semicircular canals by
      rotational acceleration and the resulting vestibular evoked eye movements.
      METHODS: In this prospective, randomized, controlled study, medical students at a
      university hospital were randomly assigned to two kinds of small instructional
      groups. Students of the control group (n = 67) practiced diagnostic and
      therapeutic maneuvers for BPPV on each other, while the participants of the study
      group (n = 46) used the aVOR app as a virtual patient in addition. At the end of
      the term, students were asked to arrange the steps of the canalith repositioning
      procedure in the correct order in a written test. RESULTS: Quality of the
      teaching media was rated significantly better in the aVOR group (two-sided Mann
      Whitney test: P < 0.00001). Significantly more students of the aVOR group than
      the control group arranged the steps of the canalith repositioning procedure
      correctly in the final exam (56.3% versus 25.9%, Fisher's exact test: P = 0.006).
      CONCLUSION: Implementation of the aVOR app as a virtual patient into small
      instructional courses is well adopted by medical students and increases their
      competence in treating BPPV.

PMID- 29579016
TI  - Platelets-to-lymphocyte ratio as a predictor of liver fibrosis and insulin
      resistance in hepatitis C virus infection: more evidence is needed.

PMID- 29579018
TI  - Using Black Bone Magnetic Resonance Imaging in Craniofacial Virtual Surgical
      Planning: A Comparative Cadaver Study.
AB  - BACKGROUND: The use of magnetic resonance imaging (MRI) for virtual surgical
      planning has not yet been described. In the United States, over 600,000 computed
      tomographic (CT) scans are performed annually on children, who are at higher risk
      than adults of developing cancer caused by ionizing radiation. The aim of this
      study was to demonstrate whether three-dimensionally-printed craniofacial
      surgical guides created from "black bone" MRI are comparable in accuracy to those
      created from CT scans. METHODS: A mock craniosynostosis surgery translocating
      four calvarial segments was virtually planned and performed in 10 cadavers. For
      five specimens, planning was performed and three-dimensionally-printed guides
      were created using black bone MRI scans. Five specimens underwent standard
      planning using CT scans. Reconstructed skulls underwent CT scans and three
      dimensional reconstruction. Accuracy was compared to that of virtually planned
      surgeries. RESULTS: The preoperative black bone MRI scan had an average deviation
      from the preoperative CT scan of 1.37 mm. There was no statistically significant
      difference in the fit accuracy of MRI versus CT-created guides. Average deviation
      of postoperative anatomy from preoperative plan was within 1.5 mm for guides
      created from either scanning modality, with no statistically significant
      difference in accuracy between the two methods. Planned versus postoperative
      skull volume was not statistically significantly different when MRI versus CT was
      used. CONCLUSIONS: This study demonstrates that virtual surgical planning and
      three-dimensional craniofacial surgical guide creation can be performed using
      black bone MRI with accuracy comparable to that of CT. This could dramatically
      reduce radiation exposure of craniofacial reconstruction patients.

PMID- 29579019
TI  - Long-Term Outcomes of Smile Reconstruction in Mobius Syndrome.
AB  - BACKGROUND: Gracilis muscle transplant is the standard of care for smile
      reconstruction in children with Mobius syndrome. The authors describe the long
      term clinical efficacy, durability, and psychosocial impact of this approach at a
      mean follow-up of 20 years. METHODS: Patients with Mobius syndrome who underwent
      gracilis muscle transfer between 1985 and 2005 were included in the study. The
      authors assessed midfacial movements using photographs and Scaled Measurement of
      Improvement in Lip Excursion measure, administered the patient-reported Facial
      Clinimetric Evaluation Scale, and used semistructured interviews. RESULTS: The
      mean age at surgery was 13.2 +/-10.6 years and the mean follow-up was 20.4 +/-
      4.4 years postoperatively. Twenty-two gracilis muscle transplants were performed,
      all innervated by the motor nerve to the masseter. Photographic analysis using
      Scaled Measurement of Improvement in Lip Excursion software demonstrated that
      movement of the muscle was unchanged 20 years after surgery. Smile symmetry was
      stable long term. The overall mean Facial Clinimetric Evaluation score of the
      cohort was 62.3 +/- 12.0. Facial comfort (86.4 +/- 21.2) and social function
      (69.9 +/- 18.5) subdomains were the highest. Although the facial movement
      subdomain score was 35.6 +/- 12.4, the score related to smiling alone was 84.1 +/
      20.2, indicating satisfaction with the midfacial reconstruction. Interview
      responses indicated high satisfaction with surgery; fulfilled expectations of
      social acceptance; improved communication; enhanced self-confidence; and a sense
      of increased facial symmetry, spontaneity, and smile excursion. CONCLUSION:
      Segmental gracilis muscle transplantation provides long-lasting, durable
      improvements in objective and patient-reported measures of facial function.

PMID- 29579020
TI  - Quality of Life in Adults with Nonsyndromic Craniosynostosis.
AB  - BACKGROUND: Although studies have analyzed quality of life in children with
      nonsyndromic craniosynostosis, to date nobody has investigated long-term quality
      of life in adults with nonsyndromic craniosynostosis. The purpose of this study
      was to compare quality of life in adult nonsyndromic craniosynostosis patients
      with a cohort of unaffected controls. METHODS: The authors queried their
      institution's prospectively maintained craniofacial registry for nonsyndromic
      craniosynostosis patients aged 18 years and older, and administered the validated
      World Health Organization Quality of Life Biomedical Research and Education
      Foundation questionnaire. Responses were compared, using a two-sample t test, to
      an age-matched U.S. normative database provided by the World Health Organization.
      RESULTS: One hundred fifty-one adults met inclusion criteria: 52 were
      successfully contacted and 32 completed the questionnaire. Average age of
      respondents was 23.0 +/- 6.1 years (range, 18.1 to 42.1 years). Nonsyndromic
      craniosynostosis patients had a superior quality of life compared with
      comparative norms in all domains: physical health (17.8 +/- 2.7 versus 15.5 +/-
      3.2; p < 0.001), psychological (16.3 +/- 2.9 versus 13.8 +/- 3.2; p < 0.001),
      social (16.9 +/- 2.6 versus 13.2 +/- 3.6; p < 0.001), and environmental (17.2 +/-
      2.5 versus 11.7 +/- 2.7; p < 0.001). Comparison between single-suture subtypes
      revealed no difference in any quality-of-life domain (p > 0.05). CONCLUSIONS:
      Adult patients previously treated for nonsyndromic craniosynostosis perceive
      their quality of life to be high, superior to that of a normative U.S. SAMPLE:
      Future work will seek to analyze additional patients and better understand the
      reasons behind these findings.

PMID- 29579021
TI  - Genetics of Nonsyndromic Craniosynostosis.
AB  - Occurring once in every 2000 live births, craniosynostosis is one of the most
      frequent congenital anomalies encountered by the craniofacial surgeon. Syndromic
      craniosynostoses account for approximately 15 percent of cases and demonstrate
      Mendelian patterns of inheritance with well-established genetic causes; however,
      nonsyndromic craniosynostoses, which account for approximately 85 percent of
      cases, are genetically heterogeneous and largely unexplored. Nonsyndromic
      craniosynostosis is sporadic in more than 95 percent of affected families; thus,
      surgeons have suggested for decades that nonsyndromic craniosynostosis is likely
      a fluke occurrence. Contrary to this, recent studies have established that
      genetics underlie a substantial fraction of nonsyndromic craniosynostosis risk.
      Given the predominantly sporadic occurrence of disease, parents are often
      bewildered by the primary occurrence of nonsyndromic craniosynostosis or even
      recurrence in their own families and request genetic testing. Existing genetic
      testing panels are useful when the phenotype strongly resembles a known syndrome,
      wherein the risk of disease recurrence can be accurately predicted for future
      offspring of the parents and the future offspring of the affected child. The
      diagnostic utility of existing panels for nonsyndromic craniosynostosis, however,
      is extremely low, and these tests are quite costly. Recent genetic studies have
      identified several novel genes and pathways that cause nonsyndromic
      craniosynostosis, providing genetic evidence linking the causes of syndromic and
      nonsyndromic craniosynostoses, and allowing for genotype-based prediction of risk
      of recurrence in some nonsyndromic families. Based on analysis of exome sequence
      data from 384 families, the authors provide recommendations for a new genetic
      testing protocol for children with nonsyndromic craniosynostosis, which include
      testing nonsyndromic cases of sagittal, metopic, and coronal craniosynostosis.

PMID- 29579022
TI  - New Developments Are Improving Flexor Tendon Repair.
AB  - New developments in primary tendon repair in recent decades include stronger core
      tendon repair techniques, judicious and adequate venting of critical pulleys,
      followed by a combination of passive and active digital flexion and extension.
      During repair, core sutures over the tendon should have sufficient suture
      purchase (no shorter than 0.7 to 1 cm) in each tendon end and must be
      sufficiently tensioned to resist loosening and gap formation between tendon ends.
      Slight or even modest bulkiness in the tendon substance at the repair site is not
      harmful, although marked bulkiness should always be avoided. To expose the tendon
      ends and reduce restriction to tendon gliding, the longest annular pulley in the
      fingers (i.e., the A2 pulley) can be vented partially with an incision over its
      distal or proximal sheath no longer than 1.5 to 2 cm; the annular pulley over the
      middle phalanx (i.e., the A4 pulley) can be vented entirely. Surgeons have not
      observed adverse effects on hand function after judicious and limited venting.
      The digital extension-flexion test to check the quality of the repair during
      surgery has become increasingly routine. A wide-awake surgical setting allows
      patient to actively move the digits. After surgery, surgeons and therapists
      protect patients with a short splint and flexible wrist positioning, and are now
      moving toward out-of-splint freer early active motion. Improved outcomes have
      been reported over the past decade with minimal or no rupture during
      postoperative active motion, along with lower rates of tenolysis.

PMID- 29579023
TI  - Requirements for Successful Trachea Transplantation: A Study in the Rabbit Model.
AB  - BACKGROUND: Although creating a tracheal tube de novo might appear
      straightforward, the first clinical applications have shown that reconstruction
      of long-segment tracheal defects remains challenging. In this study, the authors
      aimed to refine the baseline requirements of successful trachea transplantation
      by means of three proof-of-concept models in the rabbit. METHODS: In each model,
      one characteristic of a perfect tracheal transplant was eliminated. The first
      model was developed to map out the immunologic response of vascularized allogenic
      trachea, transplanted without immunosuppression (n = 6). The second model studied
      (1) the need for wrapping the transplant with a highly vascularized flap and (2)
      the source of angiogenesis after autologous trachea transplantation (n = 18). In
      the third model, the authors examined the importance of an inner epithelial
      covering (n = 12). All models were compared to a control group of heterotopically
      transplanted vascularized autologous tracheae (n = 6). RESULTS: Embedded in an
      avascular matrix, allogenic chondrocytes were protected from an overt immune
      response. Orthotopic transplantation without additional external vascular wrap
      was successful in a well-vascularized environment. Nonetheless, an external
      vascular source was essential to maintain viability of the construct. Epithelial
      covering was necessary to prevent secondary healing. Epithelial migration from
      the anastomoses or graft was not sufficient to cover long-segment defects.
      CONCLUSIONS: These experiments provided ample evidence of the importance of
      baseline requirements when designing a tracheal transplant study. This study
      confirmed that different tracheal cell types possess different immunologic
      sensitivities. External revascularization, preferably in a two-stage procedure,
      and fast reepithelialization were both paramount to successful transplantation.

PMID- 29579024
TI  - Assessing Technical Performance and Determining the Learning Curve in Cleft
      Palate Surgery Using a High-Fidelity Cleft Palate Simulator.
AB  - BACKGROUND: This study assessed technical performance in cleft palate repair
      using a newly developed assessment tool and high-fidelity cleft palate simulator
      through a longitudinal simulation training exercise. METHODS: Three residents
      performed five and one resident performed nine consecutive endoscopically
      recorded cleft palate repairs using a cleft palate simulator. Two fellows in
      pediatric plastic surgery and two expert cleft surgeons also performed recorded
      simulated repairs. The Cleft Palate Objective Structured Assessment of Technical
      Skill (CLOSATS) and end-product scales were developed to assess performance. Two
      blinded cleft surgeons assessed the recordings and the final repairs using the
      CLOSATS, end-product scale, and a previously developed global rating scale.
      RESULTS: The average procedure-specific (CLOSATS), global rating, and end-product
      scores increased logarithmically after each successive simulation session for the
      residents. Reliability of the CLOSATS (average item intraclass correlation
      coefficient (ICC), 0.85 +/- 0.093) and global ratings (average item ICC, 0.91 +/-
      0.02) among the raters was high. Reliability of the end-product assessments was
      lower (average item ICC, 0.66 +/- 0.15). Standard setting linear regression using
      an overall cutoff score of 7 of 10 corresponded to a pass score for the CLOSATS
      and the global score of 44 (maximum, 60) and 23 (maximum, 30), respectively.
      Using logarithmic best-fit curves, 6.3 simulation sessions are required to reach
      the minimum standard. CONCLUSIONS: A high-fidelity cleft palate simulator has
      been developed that improves technical performance in cleft palate repair. The
      simulator and technical assessment scores can be used to determine performance
      before operating on patients.

PMID- 29579025
TI  - A Novel Small-Animal Model of Irradiated, Implant-Based Breast Reconstruction.
AB  - BACKGROUND: There is currently a need for a clinically relevant small-animal
      model for irradiated, implant-based breast reconstruction. Present models are
      inadequate in terms of suboptimal location of expander placement and mode of
      radiation delivery, correlating poorly with the human clinical scenario. The
      authors hypothesized that by delivering fractionated radiation and placing an
      expander under the scalp of the animal, they would achieve soft-tissue changes
      histologically analogous to those seen in human irradiated, implant-based breast
      reconstruction. METHODS: This study consisted of 11 immunocompetent, hairless
      rats divided into three groups as follows: untreated control (n = 3), tissue
      expanded scalps (n = 4), and fractionated irradiation plus tissue expansion of
      the scalp (n = 4). At the completion of the experiment for each group, skin
      tissue samples were analyzed histologically for vascularity, epidermal and dermal
      thickness, and collagen fiber alignment or scar formation. RESULTS: Expanded rat
      epidermis was significantly thicker and dermis was more vascular than nonexpanded
      skin. The authors observed a greater degree of collagen fiber alignment in the
      expanded group compared with nonexpanded skin. The combination of irradiation and
      expansion resulted in significant dermal thinning, vascular depletion, and
      increased scar formation compared with expanded skin alone. CONCLUSIONS: The
      authors describe a novel small-animal model for irradiated, implant-based breast
      reconstruction where histologic analysis shows structural changes in the skin
      consistent with known effects of radiation therapy and expansion in human skin.
      This model represents a significant improvement from previous ones and, as such,
      holds the potential to be used to test new therapeutic agents to improve clinical
      outcomes.

PMID- 29579026
TI  - Targeted Muscle Reinnervation: Considerations for Future Implementation in
      Adolescents and Younger Children.
AB  - Prosthetic options for patients with proximal upper limb absence are limited.
      Current above-elbow prostheses may restore basic motor functions for crucial
      activities, but they are cumbersome to operate, lack sensory feedback, and are
      often abandoned. Targeted muscle reinnervation is a novel surgical procedure that
      enhances the ability of patients with above-elbow amputations to intuitively
      control a myoelectric prosthesis. By transferring multiple severed peripheral
      nerves to a robust target muscle, targeted muscle reinnervation restores
      physiologic continuity and enables more intuitive prosthetic control. Although
      reports have been limited to adults, targeted muscle reinnervation has great
      potential for application in a pediatric population with congenital or acquired
      proximal upper limb absence. In this review, the authors describe the
      rehabilitative challenges of proximal upper limb amputees and outline the
      objectives, techniques, and outcomes of targeted muscle reinnervation. The
      authors then discuss important considerations for adapting targeted muscle
      reinnervation to pediatric patients, including cause of upper limb absence,
      central plasticity, timing of prosthesis fitting, role of the family, surgical
      feasibility, and bioethical aspects. The authors believe that carefully screened
      school-age children and adolescents with bilateral proximal upper limb absence,
      and select adolescents with unilateral proximal upper limb absence, should be
      seriously considered for targeted muscle reinnervation performed by an
      experienced surgical and rehabilitation team.

PMID- 29579027
TI  - Reply: Five Steps to Internal Mammary Vessel Preparation in Less than 15 Minutes.

PMID- 29579028
TI  - Acellular Human Dermal Allograft as a Graft for Nasal Septal Perforation
      Reconstruction.
AB  - BACKGROUND: Nasal septal perforations pose a troubling source of morbidity for
      patients and a difficult problem for the otolaryngologist. Multiple surgical
      techniques have been tried, with inconsistent success. Prosthetic nasal buttons
      also have limitations, including patient intolerance and dissatisfaction.
      Acellular human dermal allograft (AlloDerm) has been described as an alternative
      material for septal perforation repair. The authors studied objective and
      subjective outcomes, including quantification of the patient's symptoms in septal
      perforation repair with AlloDerm. METHODS: The authors performed a prospective
      cohort study of 12 patients with 1- to 2-cm anterior septal perforations who were
      recruited from a tertiary care practice. Patients with admitted smoking or
      cocaine use in the previous 3 months or vascular or granulomatous diseases were
      excluded. Subjective scores on the Sino-nasal Outcome Test-22, along with
      objective nasal endoscopy and acoustic rhinometry measures, were collected at
      baseline and 2, 4, and 12 weeks postoperatively. Patients were followed for
      reperforation 9 to 20 months postoperatively. Data were normalized to baseline
      values and analyzed using analysis of variance and Bonferroni correction.
      RESULTS: Successful closure of the septal perforation was obtained in 10 of 12
      patients and confirmed with rigid nasal endoscopy. Nasal symptom scores (Sino
      nasal Outcome Test-22 ) were significantly reduced to 52.8 percent (95 percent
      CI, 35.1 to 70.5 percent; p < 0.01) of baseline symptoms at 4 weeks
      postoperatively. At 12 weeks postoperatively, symptoms were measured at 26.6
      percent (95 percent CI, 10.9 to 42.1 percent; p < 0.01) of baseline symptoms.
      Acoustic rhinometry confirmed perforation closure, demonstrating a reduction in
      cross-sectional nasal area from baseline of 55.1 percent (95 percent CI, 37.7 to
      66.8 percent; p < 0.01). CONCLUSION: This is the first study to use objective and
      subjective measurements to confirm success with acellular dermis allograft as an
      adjunct for septal perforation repair, demonstrating a statistically significant
      reduction in patient nasal symptoms following repair. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 29579029
TI  - Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of
      the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to
      Success?

PMID- 29579030
TI  - RE: Macro textured breast implants with defined steps to minimize bacterial
      contamination around the device.

PMID- 29579031
TI  - Five Steps to Internal Mammary Vessel Preparation in Less than 15 Minutes.

PMID- 29579032
TI  - Vertical Growth Phase as a Prognostic Factor for Sentinel Lymph Node Positivity
      in Thin Melanomas: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The 2010 American Joint Committee on Cancer guidelines recommended
      consideration of sentinel lymph node biopsy for thin melanoma (Breslow thickness
      <1.0 mm) with aggressive pathologic features such as ulceration and/or high
      mitotic rate. The therapeutic benefit of biopsy-based treatment remains
      controversial. The authors conducted a meta-analysis to estimate the risk and
      outcomes of sentinel lymph node positivity in thin melanoma, and examined
      established and potential novel predictors of positivity. METHODS: Three
      databases were searched by two independent reviewers for sentinel lymph node
      positivity in patients with thin melanoma. Study heterogeneity, publication bias,
      and quality were assessed. Data collected included age, sex, Breslow thickness,
      mitotic rate, ulceration, regression, Clark level, tumor-infiltrating
      lymphocytes, and vertical growth phase. Positivity was estimated using a random
      effects model. Association of positivity and clinicopathologic features was
      investigated using meta-regression. RESULTS: Ninety-three studies were identified
      representing 35,276 patients with thin melanoma who underwent sentinel lymph node
      biopsy. Of these patients, 952 had a positive sentinel lymph node biopsy, for an
      event rate of 5.1 percent (95 percent CI, 4.1 to 6.3 percent). Significant
      associations were identified between positivity and Breslow thickness greater
      than 0.75 mm but less than 1.0 mm, mitotic rate, ulceration, and Clark level
      greater than IV. Seven studies reported on vertical growth phase, which was
      strongly associated with positivity (OR, 4.3; 95 percent CI, 2.5 to 7.7).
      CONCLUSIONS: To date, this is the largest meta-analysis to examine predictors of
      sentinel lymph node biopsy positivity in patients with thin melanoma. Vertical
      growth phase had a strong association with biopsy positivity, providing support
      for its inclusion in standardized pathologic reporting.

PMID- 29579033
TI  - Reply: Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant
      Reconstruction of the Large and Ptotic Breast: Is Preshaping of the Challenging
      Breast a Key to Success?

PMID- 29579034
TI  - Unexpected characteristics of cirrhotic liver tumors.

PMID- 29579035
TI  - Diabetes and cardiovascular disease: from new mechanisms to new therapies.
AB  - Diabetes increases the risk of cardiovascular diseases, which are the leading
      cause of mortality among diabetic patients. Although hyperglycemia is a major
      determinant of macrovascular and microvascular complications in diabetes,
      hypoglycemia and glycemic variability have also a strong influence on the
      cardiovascular system. This overview presents the current state of knowledge on
      the impact of type 2 diabetes on the cardiovascular system and new therapeutic
      strategies that have been recently developed to correct gluco-metabolic
      disturbances in patients with high cardiovascular risk, such as glucagon-like
      peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors
      and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results of several large
      randomized clinical trials (such as EMPA-REG, LEADER, SUSTAIN-6 and CANVAS)
      assessing the efficacy and safety of drugs based on new mechanisms deserve
      attention due to their beneficial impact on serious cardiovascular events,
      including cardiovascular death, myocardial infarction, and stroke. In addition,
      based on the results of recent studies and meta-analyses, an attempt was made to
      answer the questions of whether actions new drugs are mediated solely by the
      glucose lowering effect, and if indeed glycemic control affects the survival of
      patients with diabetes and cardiovascular risk, which seems of key importance
      from the clinical perspective.

PMID- 29579036
TI  - A mechanistic pan-cancer pathway model informed by multi-omics data interprets
      stochastic cell fate responses to drugs and mitogens.
AB  - Most cancer cells harbor multiple drivers whose epistasis and interactions with
      expression context clouds drug and drug combination sensitivity prediction. We
      constructed a mechanistic computational model that is context-tailored by omics
      data to capture regulation of stochastic proliferation and death by pan-cancer
      driver pathways. Simulations and experiments explore how the coordinated dynamics
      of RAF/MEK/ERK and PI-3K/AKT kinase activities in response to synergistic mitogen
      or drug combinations control cell fate in a specific cellular context. In this
      MCF10A cell context, simulations suggest that synergistic ERK and AKT inhibitor
      induced death is likely mediated by BIM rather than BAD, which is supported by
      prior experimental studies. AKT dynamics explain S-phase entry synergy between
      EGF and insulin, but simulations suggest that stochastic ERK, and not AKT,
      dynamics seem to drive cell-to-cell proliferation variability, which in
      simulations is predictable from pre-stimulus fluctuations in C-Raf/B-Raf levels.
      Simulations suggest MEK alteration negligibly influences transformation,
      consistent with clinical data. Tailoring the model to an alternate cell
      expression and mutation context, a glioma cell line, allows prediction of
      increased sensitivity of cell death to AKT inhibition. Our model mechanistically
      interprets context-specific landscapes between driver pathways and cell fates,
      providing a framework for designing more rational cancer combination therapy.

PMID- 29579037
TI  - Scabies in residential care homes: Modelling, inference and interventions for
      well-connected population sub-units.
AB  - In the context of an ageing population, understanding the transmission of
      infectious diseases such as scabies through well-connected sub-units of the
      population, such as residential care homes, is particularly important for the
      design of efficient interventions to mitigate against the effects of those
      diseases. Here, we present a modelling methodology based on the efficient
      solution of a large-scale system of linear differential equations that allows
      statistical calibration of individual-based random models to real data on scabies
      in residential care homes. In particular, we review and benchmark different
      numerical methods for the integration of the differential equation system, and
      then select the most appropriate of these methods to perform inference using
      Markov chain Monte Carlo. We test the goodness-of-fit of this model using
      posterior predictive intervals and propagate forward the resulting parameter
      uncertainty in a Bayesian framework to consider the economic cost of delayed
      interventions against scabies, quantifying the benefits of prompt action in the
      event of detection. We also revisit the previous methodology used to assess the
      safety of treatments in small population sub-units-in this context ivermectin-and
      demonstrate that even a very slight relaxation of the implicit assumption of
      homogeneous death rates significantly increases the plausibility of the
      hypothesis that ivermectin does not cause excess mortality based upon the data of
      Barkwell and Shields.

PMID- 29579038
TI  - Results of a confirmatory mapping tool for Lymphatic filariasis endemicity
      classification in areas where transmission was uncertain in Ethiopia.
AB  - BACKGROUND: The goal of the global lymphatic filariasis (LF) program is to
      eliminate the disease as a public health problem by the year 2020. The WHO
      mapping protocol that is used to identify endemic areas in need of mass drug
      administration (MDA) uses convenience-based sampling. This rapid mapping has
      allowed the global program to dramatically scale up treatment, but as the program
      approaches its elimination goal, it is important to ensure that all endemic areas
      have been identified and have received MDA. In low transmission settings, the WHO
      mapping protocol for LF mapping has several limitations. To correctly identify
      the LF endemicity of woredas, a new confirmatory mapping tool was developed to
      test older school children for circulating filarial antigen (CFA) in settings
      where it is uncertain. Ethiopia is the first country to implement this new tool.
      In this paper, we present the Ethiopian experience of implementing the new
      confirmatory mapping tool and discuss the implications of the results for the LF
      program in Ethiopia and globally. METHODS: Confirmatory LF mapping was conducted
      in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the
      regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of
      previous mapping for LF using the current WHO protocol indicated that LF
      endemicity was uncertain. Within each woreda schools were selected using either
      cluster or systematic sampling. From selected schools, a total of 18,254 children
      were tested for circulating filarial antigen (CFA) using the immuno
      chromatographic test (ICT). RESULTS: Of the 18,254 children in 45 woredas who
      participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive.
      According to the confirmatory mapping threshold, which is >=2% CFA in children 9
      14 years of age, only 3 woredas out of the total 45 had more CFA positive results
      than the threshold and thus were confirmed to be endemic; the remaining 42
      woredas were declared non-endemic. These results drastically decreased the
      estimated total population living in LF-endemic woredas in Ethiopia and in need
      of MDA by 49.1%, from 11,580,010 to 5,893,309. CONCLUSION: This study
      demonstrated that the new confirmatory mapping tool for LF can benefit national
      LF programs by generating information that not only can confirm where LF is
      endemic, but also can save time and resources by preventing MDA where there is no
      evidence of ongoing LF transmission.

PMID- 29579039
TI  - AMYCNE: Confident copy number assessment using whole genome sequencing data.
AB  - Copy number variations (CNVs) within the human genome have been linked to a
      diversity of inherited diseases and phenotypic traits. The currently used
      methodology to measure copy numbers has limited resolution and/or precision,
      especially for regions with more than 4 copies. Whole genome sequencing (WGS)
      offers an alternative data source to allow for the detection and characterization
      of the copy number across different genomic regions in a single experiment. A
      plethora of tools have been developed to utilize WGS data for CNV detection. None
      of these tools are designed specifically to accurately estimate copy numbers of
      complex regions in a small cohort or clinical setting. Herein, we present AMYCNE
      (automatic modeling functionality for copy number estimation), a CNV analysis
      tool using WGS data. AMYCNE is multifunctional and performs copy number
      estimation of complex regions, annotation of VCF files, and CNV detection on
      individual samples. The performance of AMYCNE was evaluated using AMY1A ddPCR
      measurements from 86 unrelated individuals. In addition, we validated the
      accuracy of AMYCNE copy number predictions on two additional genes (FCGR3A and
      FCGR3B) using datasets available through the 1000 genomes consortium. Finally, we
      simulated levels of mosaic loss and gain of chromosome X and used this dataset
      for benchmarking AMYCNE. The results show a high concordance between AMYCNE and
      ddPCR, validating the use of AMYCNE to measure tandem AMY1 repeats with high
      accuracy. This opens up new possibilities for the use of WGS for accurate copy
      number determination of other complex regions in the genome in small cohorts or
      single individuals.

PMID- 29579040
TI  - Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)
      Specific IgM and IgG antibodies in human sera using recombinant CCHFV
      nucleoprotein as antigen in MU-capture and IgG immune complex (IC) ELISA tests.
AB  - As the most widespread tick-borne arbovirus causing infections in numerous
      countries in Asia, Africa and Europe, Crimean-Congo Hemorrhagic Fever Virus
      (CCHFV, family Nairoviridae) was included in the WHO priority list of emerging
      pathogens needing urgent Research & Development attention. To ensure preparedness
      for potential future outbreak scenarios, reliable diagnostic tools for
      identification of acute cases as well as for performance of seroprevalence
      studies are necessary. Here, the CCHFV ortholog of the major bunyavirus antigen,
      the nucleoprotein (NP), was recombinantly expressed in E.coli, purified and
      directly labeled with horseradish peroxidase (HRP). Employing this antigen, two
      serological tests, a MU-capture ELISA for the detection of CCHFV-specific IgM
      antibodies (BLACKBOX CCHFV IgM) and an IgG immune complex (IC) ELISA for the
      detection of CCHFV-specific IgG antibodies (BLACKBOX CCHFV IgG), were developed.
      Test performance was evaluated and compared with both in-house gold standard
      testing by IgM/IgG indirect immunofluorescence (IIF) and commercially available
      ELISA tests (VectoCrimean-CHF-IgM/IgG, Vector-Best, Russia) using a serum panel
      comprising paired samples collected in Kosovo during the years 2013-2016 from 15
      patients with an acute, RT-PCR-confirmed CCHFV infection, and 12 follow-up sera
      of the same patients collected approximately one year after having overcome the
      infection. Reliably detecting IgM antibodies in all acute phase sera collected
      later than day 4 after onset of symptoms, both IgM ELISAs displayed excellent
      diagnostic and analytical sensitivity (100%, 95% confidence interval (CI): 85.2%
      100.0%). While both IgG ELISAs readily detected the high IgG titers present in
      convalescent patients approximately one year after having overcome the infection
      (sensitivity 100%, 95% CI: 73.5%-100.0%), the newly developed BLACKBOX CCHFV IgG
      ELISA was superior to the commercial IgG ELISA in detecting the rising IgG titers
      during the acute phase of the disease. While all samples collected between day 11
      and 19 after onset of symptoms tested positive in both the in-house gold standard
      IIFT and the BLACKBOX CCHFV IgG ELISA (sensitivity 100%, 95% CI: 71.5%-100.0%),
      only 27% (95% CI: 6.0%-61.0%) of those samples were tested positive in the
      commercial IgG ELISA. No false positive signals were observed in either IgM/IgG
      ELISA when analyzing a priori CCHFV IgM/IgG negative serum samples from healthy
      blood donors, malaria patients and flavivirus infected patients as well as CCHFV
      IgM/IgG IIFT negative serum samples from healthy Kosovar blood donors (for
      BLACKBOX CCHFV IgM/IgG: n = 218, 100% specificity, 95% CI: 98.3%-100.0%, for
      VectoCrimean-CHF-IgM/IgG: n = 113, 100% specificity, 95% CI: 96.8%-100.0%).

PMID- 29579041
TI  - The CSR-1 endogenous RNAi pathway ensures accurate transcriptional reprogramming
      during the oocyte-to-embryo transition in Caenorhabditis elegans.
AB  - Endogenous RNAi (endoRNAi) is a conserved mechanism for fine-tuning gene
      expression. In the nematode Caenorhabditis elegans, several endoRNAi pathways are
      required for the successful development of reproductive cells. The CSR-1 endoRNAi
      pathway promotes germ cell development, primarily by facilitating the expression
      of germline genes. In this study, we report a novel function for the CSR-1
      pathway in preventing premature activation of embryonic transcription in the
      developing oocytes, which is accompanied by a general Pol II activation. This CSR
      1 function requires its RNase activity, suggesting that, by controlling the
      levels of maternal mRNAs, CSR-1-dependent endoRNAi contributes to an orderly
      reprogramming of transcription during the oocyte-to-embryo transition.

PMID- 29579042
TI  - Genetic variants in cellular transport do not affect mesalamine response in
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Mesalamine is commonly used to treat ulcerative colitis
      (UC). Although mesalamine acts topically, in vitro data suggest that
      intracellular transport is required for its beneficial effect. Genetic variants
      in mucosal transport proteins may affect this uptake, but the clinical relevance
      of these variants has not been studied. The aim of this study was to determine
      whether variants in genes involved in cellular transport affect the response to
      mesalamine in UC. METHODS: Subjects with UC from a 6-week clinical trial using
      multiple doses of mesalamine were genotyped using a genome-wide array that
      included common exome variants. Analysis focused on cellular transport gene
      variants with a minor allele frequency >5%. Mesalamine response was defined as
      improvement in Week 6 Physician's Global Assessment (PGA) and non-response as a
      lack of improvement in Week 6 PGA. Quality control thresholds included an
      individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion
      for subjects with cryptic relatedness. All included variants met Hardy-Weinberg
      equilibrium (p>0.001). RESULTS: 457 adults with UC were included with 280
      responders and 177 non-responders. There were no common variants in transporter
      genes that were associated with response to mesalamine. The genetic risk score of
      responders was similar to that of non-responders (p = 0.18). Genome-wide variants
      demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5).
      CONCLUSIONS: Common transporter gene variants did not affect response to
      mesalamine in adult UC. The response to mesalamine may be due to rare genetic
      events or environmental factors such as the intestinal microbiome.

PMID- 29579043
TI  - Experiments in interdisciplinarity: Responsible research and innovation and the
      public good.
AB  - In Europe, responsible research and innovation (RRI) has emerged as a science
      policy measure that demands the early integration of a broad range of social
      actors and perspectives into research and development (R&D). More collaboration
      of the social sciences and humanities (SSH) with science and engineering appears
      within this policy framework as a crucial element that will enable better
      technological development. However, RRI is new to both natural scientists and SSH
      scholars, and interdisciplinary collaborations are challenging for many reasons.
      In this paper, we discuss these challenges while suggesting that what RRI can be
      in a particular project is not a given but remains an empirical question. Natural
      scientists and SSH scholars need to coresearch RRI in an experimental mode.

PMID- 29579045
TI  - From correlation to causation: Estimating effective connectivity from zero-lag
      covariances of brain signals.
AB  - Knowing brain connectivity is of great importance both in basic research and for
      clinical applications. We are proposing a method to infer directed connectivity
      from zero-lag covariances of neuronal activity recorded at multiple sites. This
      allows us to identify causal relations that are reflected in neuronal population
      activity. To derive our strategy, we assume a generic linear model of interacting
      continuous variables, the components of which represent the activity of local
      neuronal populations. The suggested method for inferring connectivity from
      recorded signals exploits the fact that the covariance matrix derived from the
      observed activity contains information about the existence, the direction and the
      sign of connections. Assuming a sparsely coupled network, we disambiguate the
      underlying causal structure via L1-minimization, which is known to prefer sparse
      solutions. In general, this method is suited to infer effective connectivity from
      resting state data of various types. We show that our method is applicable over a
      broad range of structural parameters regarding network size and connection
      probability of the network. We also explored parameters affecting its activity
      dynamics, like the eigenvalue spectrum. Also, based on the simulation of suitable
      Ornstein-Uhlenbeck processes to model BOLD dynamics, we show that with our method
      it is possible to estimate directed connectivity from zero-lag covariances
      derived from such signals. In this study, we consider measurement noise and
      unobserved nodes as additional confounding factors. Furthermore, we investigate
      the amount of data required for a reliable estimate. Additionally, we apply the
      proposed method on full-brain resting-state fast fMRI datasets. The resulting
      network exhibits a tendency for close-by areas being connected as well as inter
      hemispheric connections between corresponding areas. In addition, we found that a
      surprisingly large fraction of more than one third of all identified connections
      were of inhibitory nature.

PMID- 29579044
TI  - Suppressed plasmablast responses in febrile infants, including children with
      Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD), the leading cause of acquired heart disease in
      children, primarily affects infants and toddlers. Investigations on immune
      responses during KD are hampered by a limited understanding of normal immune
      responses in these ages. It's well known that Infants have poorer vaccine
      responses and difficulty with maintaining prolonged serum immunity, but there are
      few studies on human infants detailing immune deficiencies. Limited studies
      propose an inability to maintain life-long bone marrow plasma cells. Plasmablasts
      are a transitional cell form of B cells that lead to long-term Plasma cells.
      Plasmablasts levels rise in the peripheral blood after exposure to a foreign
      antigen. In adult studies, these responses are both temporally and functionally
      well characterized. To date, there have been few studies on plasmablasts in the
      predominant age range of KD. METHODS: Children presenting to an urban pediatric
      emergency room undergoing laboratory evaluation, who had concern of KD or had
      fever and symptoms overlapping those of KD, were recruited. Peripheral blood
      mononuclear cells were isolated and evaluated utilizing flow cytometry with
      specific B cell markers from 18 KD subjects and 69 febrile controls. RESULTS:
      Plasmablast numbers and temporal formation are similar between infectious disease
      controls and KD subjects. In both groups, infants have diminished plasmablast
      responses compared to older children. CONCLUSION: In this single-time point
      survey, infants have a blunted peripheral plasmablast response. Overall, similar
      plasmablast responses in KD and controls support an infectious disease
      relationship to KD. Future time-course studies of plasmablasts in infants are
      warranted as this phenomenon may contribute to observed immune responses in this
      age group.

PMID- 29579046
TI  - Scrub typhus point-of-care testing: A systematic review and meta-analysis.
AB  - BACKGROUND: Diagnosing scrub typhus clinically is difficult, hence laboratory
      tests play a very important role in diagnosis. As performing sophisticated
      laboratory tests in resource-limited settings is not feasible, accurate point-of
      care testing (POCT) for scrub typhus diagnosis would be invaluable for patient
      diagnosis and management. Here we summarise the existing evidence on the accuracy
      of scrub typhus POCTs to inform clinical practitioners in resource-limited
      settings of their diagnostic value. METHODOLOGY/PRINCIPAL FINDINGS: Studies on
      POCTs which can be feasibly deployed in primary health care or outpatient
      settings were included. Thirty-one studies were identified through PubMed and
      manual searches of reference lists. The quality of the studies was assessed with
      the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n
      = 14/31) of the included studies were of moderate quality. Meta-analysis showed
      the pooled sensitivity and specificity of commercially available
      immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37-0.86) and 92.0% (95%
      CI 0.83-0.97), respectively. There was a significant and high degree of
      heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71-98.24 for
      sensitivity and I2 value = 98.17%, 95% CI 97.67-98.67 for specificity).
      Significant heterogeneity was observed for total number of samples between
      studies (p = 0.01), study design (whether using case-control design or not, p =
      0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score
      (p = 0.01). CONCLUSIONS/SIGNIFICANCE: There was significant heterogeneity between
      the scrub typhus POCT diagnostic accuracy studies examined. Overall, the
      commercially available scrub typhus ICTs demonstrated better performance when
      'ruling in' the diagnosis. There is a need for standardised methods and reporting
      of diagnostic accuracy to decrease between-study heterogeneity and increase
      comparability among study results, as well as development of an affordable and
      accurate antigen-based POCT to tackle the inherent weaknesses associated with
      serological testing.

PMID- 29579048
TI  - Oxygen-sensing neurons reciprocally regulate peripheral lipid metabolism via
      neuropeptide signaling in Caenorhabditis elegans.
AB  - The mechanisms by which the sensory environment influences metabolic homeostasis
      remains poorly understood. In this report, we show that oxygen, a potent
      environmental signal, is an important regulator of whole body lipid metabolism.
      C. elegans oxygen-sensing neurons reciprocally regulate peripheral lipid
      metabolism under normoxia in the following way: under high oxygen and food
      absence, URX sensory neurons are activated, and stimulate fat loss in the
      intestine, the major metabolic organ for C. elegans. Under lower oxygen
      conditions or when food is present, the BAG sensory neurons respond by repressing
      the resting properties of the URX neurons. A genetic screen to identify
      modulators of this effect led to the identification of a BAG-neuron-specific
      neuropeptide called FLP-17, whose cognate receptor EGL-6 functions in URX
      neurons. Thus, BAG sensory neurons counterbalance the metabolic effect of
      tonically active URX neurons via neuropeptide communication. The combined
      regulatory actions of these neurons serve to precisely tune the rate and extent
      of fat loss to the availability of food and oxygen, and provides an interesting
      example of the myriad mechanisms underlying homeostatic control.

PMID- 29579047
TI  - Bioinformatic characterization of the Anoctamin Superfamily of Ca2+-activated ion
      channels and lipid scramblases.
AB  - Our laboratory has developed bioinformatic strategies for identifying distant
      phylogenetic relationships and characterizing families and superfamilies of
      transport proteins. Results using these tools suggest that the Anoctamin
      Superfamily of cation and anion channels, as well as lipid scramblases, includes
      three functionally characterized families: the Anoctamin (ANO), Transmembrane
      Channel (TMC) and Ca2+-permeable Stress-gated Cation Channel (CSC) families; as
      well as four families of functionally uncharacterized proteins, which we refer to
      as the Anoctamin-like (ANO-L), Transmembrane Channel-like (TMC-L), and CSC-like
      (CSC-L1 and CSC-L2) families. We have constructed protein clusters and trees
      showing the relative relationships among the seven families. Topological analyses
      suggest that the members of these families have essentially the same topologies.
      Comparative examination of these homologous families provides insight into
      possible mechanisms of action, indicates the currently recognized organismal
      distributions of these proteins, and suggests drug design potential for the
      disease-related channel proteins.

PMID- 29579049
TI  - Fecal microbiota in the female prairie vole (Microtus ochrogaster).
AB  - We examined the fecal microbiota of female prairie voles. This species is
      socially and, likely, sexually monogamous, and thus serves as a valuable model in
      which to examine the interaction between the microbiota-gut-brain axis and social
      behavior. At present, little is known about the gastrointestinal microbiota of
      prairie voles; therefore, we performed a first characterization of the fecal
      microbiota using 16S rRNA gene amplicon sequencing. Semiconductor sequencing
      technology on an Ion Torrent PGM platform was used to assess the composition of
      fecal microbiotas from twelve female prairie voles. Following quality filtering,
      1,017,756 sequencing reads were classified from phylum to genus level. At the
      phylum level, Firmicutes, Bacteroidetes, and Saccharibacteria were the
      predominant taxa, while the Bacteriodales, Erysipelotrichaceae, Ruminococcaceae,
      and Lachnospiraceae contributed the most dominant microbial groups and genera.
      Microbial community membership was most similar between vole sibling pairs, but
      consideration of taxon abundances weakened these associations. The
      interdependence of host factors such as genetics and behavior with the
      gastrointestinal microbiota is likely to be particularly pronounced in prairie
      voles. Our pilot characterization of the prairie vole intestinal microbiota
      revealed a microbial community composition remarkably consistent with the
      monogastric alimentary system of these rodents and their diet rich in complex
      plant carbohydrates. The highly social nature of these animals poses specific
      challenges to microbiome analyses that nonetheless are valuable for advancing
      research on the microbiota-gut-brain-behavior axis. Our study provides an
      important basis for future microbiome research in this emerging model organism
      for studying social behavior.

PMID- 29579050
TI  - Seroepidemiology of helminths and the association with severe malaria among
      infants and young children in Tanzania.
AB  - The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is
      high, particularly in Africa, and co-infection is common. However, the effects of
      filarial infection on the risk of severe malaria are unknown. We used the
      remaining serum samples from a large cohort study in Muheza, Tanzania to describe
      vector-borne filarial sero-reactivity among young children and to identify
      associations between exposure to filarial parasites and subsequent severe malaria
      infections. We identified positive filarial antibody responses (as well as
      positive antibody responses to Strongyloides stercoralis) among infants as young
      as six months. In addition, we found a significant association between filarial
      seropositivity at six months of age and subsequent severe malaria. Specifically,
      infants who developed severe malaria by one year of age were 3.9 times more
      likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial
      antigen at six months of age compared with infants who did not develop severe
      malaria.

PMID- 29579051
TI  - Eutrophication and predator presence overrule the effects of temperature on
      mosquito survival and development.
AB  - Adequate predictions of mosquito-borne disease risk require an understanding of
      the relevant drivers governing mosquito populations. Since previous studies have
      focused mainly on the role of temperature, here we assessed the effects of other
      important ecological variables (predation, nutrient availability, presence of
      conspecifics) in conjunction with the role of temperature on mosquito life
      history parameters. We carried out two mesocosm experiments with the common brown
      house mosquito, Culex pipiens, a confirmed vector for West Nile Virus, Usutu and
      Sindbis, and a controphic species; the harlequin fly, Chironomus riparius. The
      first experiment quantified interactions between predation by Notonecta glauca L.
      (Hemiptera: Notonectidae) and temperature on adult emergence. The second
      experiment quantified interactions between nutrient additions and temperature on
      larval mortality and adult emergence. Results indicate that 1) irrespective of
      temperature, predator presence decreased mosquito larval survival and adult
      emergence by 20-50%, 2) nutrient additions led to a 3-4-fold increase in mosquito
      adult emergence and a 2-day decrease in development time across all temperature
      treatments, 3) neither predation, nutrient additions nor temperature had strong
      effects on the emergence and development rate of controphic Ch. riparius. Our
      study suggests that, in addition to of effects of temperature, ecological bottom
      up (eutrophication) and top-down (predation) drivers can have strong effects on
      mosquito life history parameters. Current approaches to predicting mosquito-borne
      disease risk rely on large-scale proxies of mosquito population dynamics, such as
      temperature, vegetation characteristics and precipitation. Local scale management
      actions, however, will require understanding of the relevant top-down and bottom
      up drivers of mosquito populations.

PMID- 29579052
TI  - Correction: MAGPIE: Simplifying access and execution of computational models in
      the life sciences.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005898.].

PMID- 29579053
TI  - Emergence of opinion leaders in reference networks.
AB  - Individuals often refer to opinions of others when they make decisions in the
      real world. Our question is how the people's reference structure self-organizes
      when people try to provide correct answers by referring to more accurate agents.
      We constructed an adaptive network model, in which each node represents an agent
      and each directed link represents a reference. In every iteration round within
      our model, each agent makes a decision sequentially by following the majority of
      the reference partners' opinions and rewires a reference link to a partner if the
      partner's performance falls below a given threshold. The value of this threshold
      is common for all agents and represents the performance assessment severity of
      the population. We found that the reference network self-organizes into a
      heterogeneous one with a nearly exponential in-degree (the number of followers)
      distribution, where reference links concentrate around agents with high intrinsic
      ability. In this heterogeneous network, the decision-making accuracy of agents
      improved on average. However, the proportion of agents who provided correct
      answers showed strong temporal fluctuation compared to that observed in the case
      in which each agent refers to randomly selected agents. We also found a
      counterintuitive phenomenon in which reference links concentrate more around high
      ability agents and the population became smarter on average when the rewiring
      threshold was set lower than when it was set higher.

PMID- 29579054
TI  - The expression and function of KCNQ potassium channels in human chorionic plate
      arteries from women with normal pregnancies and pre-eclampsia.
AB  - Pre-eclampsia is associated with altered maternal and placental vascular
      reactivity. Kv7 channels (encoded by KCNQ 1-5 genes) are a potential contributor
      to the regulation of vascular tone in CPAs (chorionic plate arteries) during
      normal pregnancy. The aim of this study is to establish the expression profile of
      KCNQ subunits in CPAs taken from women with preeclampsia or normotensive women
      and to examine the functional relevance of the Kv7 channels on an altered
      expression profile of KCNQ subunits. The effects of Kv7 channel modulators on
      CPAs were investigated by tension measurement. Quantitative PCR experiments were
      used to analyze the expression of KCNQ genes. Western blotting and
      immunofluorescence were both used to analyze the protein expression of Kv7
      channels. Finally, in CPAs from normotensive women, the Kv7 channel blocker XE991
      increased arterial basal tone and U46619-induced contraction, and pre-contracted
      CPAs (10-7 M U46619) exhibited significant relaxation following treatment with
      Retigabine(Kv7.2-7.5 activator) and BMS-204352(Kv7.2-7.5 activator). However, ICA
      27243(selective KCNQ2 and KCNQ3 activator) and ML277(selective KV7.1 activator)
      had no significant effect on tension in the pre-contracted CPAs. Conversely,
      compared with CPAs from normotensive women, the effects of XE991 on basal tone
      and agonist (U46619)-induced contractions in CPAs from women with preeclampsia
      were markedly attenuated. Moreover, the relaxation effects of Retigabine and BMS
      204352 on pre-contracted CPA vessels from women with pre-eclampsia were also
      markedly down-regulated. Interestingly, the relaxation ability of ICA-27243 in
      pre-contracted CPA vessels in women with pre-eclampsia was enhanced. The mRNA of
      KCNQ3 was specifically up-regulated, whereas those for KCNQ4 and KCNQ5 were down
      regulated in CPAs from women with pre-eclampsia compared with those in
      normotensive women. Similar observations were found in a subsequent analysis of
      protein expression of KCNQ genes 3-5. Thus, down-regulated Kv7 channel function
      in tension regulation of CPAs in women with pre-eclampsia could be associated
      with considerably altered expression profiles of Kv7 subunits.

PMID- 29579055
TI  - Proportion and predictors of transfusion-transmissible infections among blood
      donors in North Shewa Zone, Central North Ethiopia.
AB  - BACKGROUND: Transfusion-transmissible infections (TTIs) pose a significant
      challenge for the availability and safety of blood transfusion. The aim of this
      study was to investigate the prevalence and risk factors for TTIs among blood
      donors in North Shewa zone, central North Ethiopia. METHODS: A retrospective
      survey of blood donors' medical records was conducted from April 2014 to June
      2017 to assess the presence of hepatitis B virus (HBV), hepatitis C virus (HCV),
      human immunodeficiency virus (HIV), and syphilis infections. Descriptive
      statistics such as percentage, median and interquartile range were used to
      summarize the data. RESULTS: Out of 8460 donations, 207 (2.4%, 95% CI 2.06-2.71%)
      had serological evidence of infection with at least one pathogen. Four of the
      blood donors (0.047%) had co-infection with more than one pathogen; 2HIV/HBV and
      2HIV/syphilis. The overall prevalence of HBV, HCV, HIV, and syphilis among the
      donors were 1.2% (95% CI 0.98-1.45%), 0.32% (95% CI 0.2-0.44%), 0.25% (95% CI
      0.14-0.35%), and 0.71% (95% CI 0.53-0.89%) respectively. Male sex was
      significantly associated with higher risk of HBV (OR 1.75, 95% CI 1.1-2.8) and
      syphilis sero-reactivity (OR 4.5, 95% CI1.9-10.5). Farmers and older donors were
      found to be at a higher risk for syphilis seropositivity. CONCLUSION: The
      prevalence of TTIs among blood donors in North Shewa zone was relatively low
      compared to those of other geographic places in Ethiopia. However, TTIs remain a
      concern for the availability and safety of blood transfusion as they are still
      prevalent in the study area. Therefore, more efforts are required to ensure the
      safety of blood supply and transfusions.

PMID- 29579056
TI  - Empathizing-systemizing cognitive styles: Effects of sex and academic degree.
AB  - This study tests if the drives to empathize (E) and systemize (S), measured by
      the Systemizing Quotient-Revised (SQ-R) and Empathy Quotient (EQ), show effects
      of sex and academic degree. The responses of 419 students from the Humanities and
      the Physical Sciences were analyzed in terms of the E-S theory predictions.
      Results confirm that there is an interaction between sex, degree and the drive to
      empathize relative to systemize. Female students in the Humanities on average had
      a stronger drive to empathize than to systemize in comparison to males in the
      Humanities. Male students in the Sciences on average had a stronger drive to
      systemize than to empathize in comparison to females in the Sciences. Finally,
      students in the sciences on average had a stronger drive to systemize more than
      to empathize, irrespective of their sex. The reverse is true for students in the
      Humanities. These results strongly replicate earlier findings.

PMID- 29579057
TI  - Exacerbation induces a microbiota shift in sputa of COPD patients.
AB  - Little is known about the microbiota shift induced by exacerbation in chronic
      obstructive pulmonary disease (COPD) patients. The sputa microbiota of COPD
      patients was evaluated when clinically stable and during acute exacerbations of
      the disease. Sputa microbiota was analyzed using 16S ribosomal RNA gene
      pyrosequencing and quantitative polymerase chain reaction-based pathogen
      detection. Nine COPD patients were enrolled. Pyrosequencing of 16S rRNA genes
      identified 2,267 unique bacterial operational taxonomic units. Principal
      microbiota shifts during exacerbation were in either Proteobacteria, Firmicutes
      or Bacteroidetes. Streptococcus and Moraxella levels were detected during
      exacerbation in severe (Global Initiative for Chronic Obstructive Lung Disease 3)
      COPD patients. Most of the clinically-important genera found in the sputum with
      the pyrosequencing of 16S rRNA gene correlated with specific quantitative
      polymerase chain reactions for bacteria while respiratory viruses were nearly
      absent. Sputum microbiotas of exacerbated COPD patients are complex. This pilot
      study shows a clear shift in the microbiota of patients during exacerbation. The
      nature of this shift varies from patient to patient in such a way that the
      treatment should be patient-specific. Further studies are needed to establish the
      impact of microbial exacerbations on the pulmonary microbiota.

PMID- 29579058
TI  - Comparative oncology approach to drug repurposing in osteosarcoma.
AB  - BACKGROUND: Osteosarcoma is an orphan disease for which little improvement in
      survival has been made since the late 1980s. New drug discovery for orphan
      diseases is limited by the cost and time it takes to develop new drugs.
      Repurposing already approved FDA-drugs can help overcome this limitation. Another
      limitation of cancer drug discovery is the lack of preclinical models that
      accurately recapitulate what occurs in humans. For OS using dogs as a model can
      minimize this limitation as OS in canines develops spontaneously, is locally
      invasive and metastasizes to the lungs as it does in humans. METHODS: In our
      present work we used high-throughput screens to identify drugs from a library of
      2,286 FDA-approved drugs that demonstrated selective growth inhibition against
      both human and canine OS cell lines. The identified lead compound was then tested
      for synergy with 7 other drugs that have demonstrated activity against OS. These
      results were confirmed with in vitro assays and an in vivo murine model of OS.
      RESULTS: We identified 13 drugs that demonstrated selective growth inhibition
      against both human and canine OS cell lines. Auranofin was selected for further
      in vitro combination drug screens. Auranofin showed synergistic effects with
      vorinostat and rapamycin on OS viability and apoptosis induction. Auranofin
      demonstrated single-agent growth inhibition in both human and canine OS
      xenografts, and cooperative growth inhibition was observed in combination with
      rapamycin or vorinostat. There was a significant decrease in Ki67-positive cells
      and an increase in cleaved caspase-3 levels in tumor tissues treated with a
      combination of auranofin and vorinostat or rapamycin. CONCLUSIONS: Auranofin,
      alone or in combination with rapamycin or vorinostat, may be useful new treatment
      strategies for OS. Future studies may evaluate the efficacy of auranofin in dogs
      with OS as a prelude to human clinical evaluation.

PMID- 29579059
TI  - Cardiac findings in infants with in utero exposure to Zika virus- a cross
      sectional study.
AB  - BACKGROUND: Antenatal exposure to Zika virus (ZIKV) is related to severe
      neurological manifestations. A previous study in Brazil reported an increased
      incidence of non-severe congenital heart defects in infants with diagnosis of
      congenital Zika syndrome but without laboratory confirmation of ZIKV infection in
      the mother or infant. The objective of this study is to report echocardiographic
      (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV.
      METHODOLOGY: Cross sectional study of cardiologic assessments of infants born
      between November 2015 and January 2017 with confirmed vertical exposure to ZIKV
      in Rio de Janeiro, Brazil. RESULTS: The study enrolled 120 children with a median
      age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97
      children (80,8%) through positive maternal polymerase chain reaction (PCR)
      results during pregnancy or a positive PCR result at birth; 23 additional
      children (19.2%) had maternal positive PCR results during pregnancy and
      postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO.
      Thirteen infants (10.8%) had major cardiac defects (atrial septal defect,
      ventricular septal defect, patent ductus arteriosus). None of the defects were
      severe. The frequency of major defects was higher in infants whose mothers had a
      rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System
      (CNS) imaging postnatally or were preterm. CONCLUSIONS: Infants with in utero
      ZIKV exposure have a higher prevalence of major cardiac defects, however none
      were severe enough to require immediate intervention. For this reason, guidelines
      for performance of postnatal ECHO in this population should follow general
      newborn screening guidelines, which significantly reduces the burden of
      performing emergent fetal or neonatal ECHOs in a setting where resources are not
      available, such as most Brazilian municipalities.

PMID- 29579061
TI  - Effects of cognitive impairment and functional limitation on depressive symptoms
      among community-dwelling older Korean immigrants in the U.S.
AB  - The present study examined the effects of cognitive impairment and functional
      limitation on depressive symptoms among older Korean American immigrants. The
      sample was drawn from a cross-sectional survey of 210 older Korean immigrants
      (aged 65 years or older) in Los Angeles County. Based on robust hierarchical
      regression, the study found that cognitive ability and functional status were
      significant explanatory factors related to depressive symptoms among older Korean
      immigrants. In addition, the interaction of instrumental activities of daily
      living (IADL) and cognitive function (MMSE) had a significant effect on
      depressive symptoms. This finding suggests that older Korean immigrants in the
      U.S. who experience deficits in cognitive function and/or IADL performance are
      vulnerable to psychological distress as indicated by depressive symptoms.
      Recommendations include implementing culturally-responsive health interventions
      aimed at enabling accessibility to dementia care services and supporting
      improvement of IADL performance among older Korean American immigrants.

PMID- 29579060
TI  - Role of oceanography in shaping the genetic structure in the North Pacific hake
      Merluccius productus.
AB  - Determining the relative influence of biotic and abiotic factors on genetic
      connectivity among populations remains a major challenge in evolutionary biology
      and in the management and conservation of species. North Pacific hake (Merluccius
      productus) inhabits upwelling regions in the California Current ecosystem from
      the Gulf of California to the Gulf of Alaska. In this study, we examined
      mitochondrial DNA (mtDNA) and microsatellite variation to estimate levels of
      genetic differentiation of M. productus in relation to the role of oceanographic
      features as potential barriers to gene flow. Samples were obtained from nine
      sites spanning a large part of the geographic range of the species, from Puget
      Sound, Washington to Costa Rica. The microsatellite results revealed three
      genetically discrete populations: one spanning the eastern Pacific coast, and two
      apparently resident populations circumscribed to the Puget Sound and the northern
      Gulf of California (FST = 0.032, p = 0.036). Cytochrome b sequence data indicated
      that isolation between the Puget Sound and northern Gulf of California
      populations from the coastal Pacific were recent phenomena (18.5 kyr for Puget
      Sound and 40 kyr for the northern Gulf of California). Oceanographic data
      obtained from the Gulf of California support the hypothesis that permanent fronts
      within the region, and strong gradients at the entrance to the Gulf of California
      act as barriers to gene flow. A seascape genetics approach found significant
      genetic-environment associations, where the daytime sea surface temperature and
      chlorophyll concentrations were the best predictive variables for the observed
      genetic differentiation. Considering the potential causes of genetic isolation
      among the three populations, e.g. spawning areas in different latitudes
      associated with upwelling processes, oceanographic barriers, asymmetric migration
      and specialized diet, oceanographic barriers appear to be a likely mechanism
      restricting gene flow.

PMID- 29579062
TI  - Heterogeneity in glycan composition on the surface of HIV-1 envelope determines
      virus sensitivity to lectins.
AB  - Lectins that target N-glycans on the surface of HIV-1 envelope (Env) glycoprotein
      have the potential for use as antiviral agents. Although progress has been made
      in deciphering the molecular details of lectin and Env glycan interaction,
      further studies are needed to better understand Env glycan heterogeneity among
      HIV-1 isolates and its influence on virus-neutralization sensitivity to lectins.
      This study evaluated a panel of lectins with fine specificity for distinct
      oligosaccharides and assessed their ability to inhibit infection of HIV-1 viruses
      known to have differing sensitivity to anti-HIV Env antibodies. The results
      showed that HIV-1 isolates have different sensitivity to lectins specific for
      alpha1-3Man, alpha1-6Man, and alpha1-2Man binding lectins. Considering that
      lectins exclusively recognize the oligosaccharide components of virus Env, these
      data suggest that glycan heterogeneity among HIV-1 isolates may explain this
      differential sensitivity. To evaluate this further, chronic and acute viruses
      were produced in the presence of different glycosidase inhibitors to express more
      homogenous glycans. Viruses enriched for alpha1-2Man terminating Man5-9GlcNAc2
      glycans became similarly sensitive to alpha1-2Man-binding lectins. The alpha1
      3Man- and alpha1-6Man-binding lectins also were more potent against viruses
      expressing predominantly Man5GlcNAc2 and hybrid type glycans with terminal alpha1
      3Man and alpha1-6Man. Furthermore, lectin-mediated inhibition was competitively
      alleviated by mannan and this effect was augmented by enrichment of mannose-type
      glycans on the virus. In addition, while Env of viruses enriched with mannose
      type glycans were sensitive to Endo-H deglycosylation, Env of untreated viruses
      were partially resistant, indicating that HIV-1 Env glycans are heterogeneously
      comprised of complex, hybrid, and mannose types. Overall, our data demonstrate
      that HIV-1 isolates display differential sensitivity to lectins, in part due to
      the microheterogeneity of N-linked glycans expressed on the surface of the virus
      Env glycoprotein.

PMID- 29579064
TI  - Neural processing of food and emotional stimuli in adolescent and adult anorexia
      nervosa patients.
AB  - BACKGROUND: A constant preoccupation with food and restrictive eating are main
      symptoms of anorexia nervosa (AN). Imaging studies revealed aberrant neural
      activation patterns in brain regions processing hedonic and reward reactions as
      well as-potentially aversive-emotions. An imbalance between so called "bottom-up"
      and "top-down" control areas is discussed. The present study is focusing on
      neural processing of disease-specific food stimuli and emotional stimuli and its
      developmental course in adolescent and adult AN patients and could offer new
      insight into differential mechanisms underlying shorter or more chronic disease.
      METHODS: 33 adolescents aged 12-18 years (15 AN patients, 18 control
      participants) and 32 adult women (16 AN patients, 16 control participants)
      underwent functional magnetic resonance imaging (fMRI, 3T high-field scanner)
      while watching pictures of high and low-calorie food and affective stimuli.
      Afterwards, they rated subjective valence of each picture. FMRI data analysis was
      performed using a region of interest based approach. RESULTS: Pictures of high
      calorie food items were rated more negatively by AN patients. Differences in
      activation between patients and controls were found in "bottom up" and "top down"
      control areas for food stimuli and in several emotion processing regions for
      affective stimuli which were more pronounced in adolescents than in adults.
      CONCLUSION: A differential pattern was seen for food stimuli compared to
      generally emotion eliciting stimuli. Adolescents with AN show reduced processing
      of affective stimuli and enhanced activation of regions involved in "bottom up"
      reward processing and "top down" control as well as the insula with regard to
      food stimuli with a focus on brain regions which underlie changes during
      adolescent development. In adults less clear and less specific activation
      differences were present, pointing towards a high impact that regions undergoing
      maturation might have on AN symptoms.

PMID- 29579063
TI  - In silico identification of microRNAs predicted to regulate N
      myristoyltransferase and Methionine Aminopeptidase 2 functions in cancer and
      infectious diseases.
AB  - Protein myristoylation is a key protein modification carried out by N
      Myristoyltransferase (NMT) after Methionine aminopeptidase 2 (MetAP2) removes
      methionine from the amino-terminus of the target protein. Protein myristoylation
      by NMT augments several signaling pathways involved in a myriad of cellular
      processes, including developmental pathways and pathways that when dysregulated
      lead to cancer or immune dysfunction. The emerging evidence pointing to NMT
      mediated myristoylation as a major cellular regulator underscores the importance
      of understanding the framework of this type of signaling event. Various studies
      have investigated the role that myristoylation plays in signaling dysfunction by
      examining differential gene or protein expression between normal and diseased
      states, such as cancers or following HIV-1 infection, however no study exists
      that addresses the role of microRNAs (miRNAs) in the regulation of
      myristoylation. By performing a large scale bioinformatics and functional
      analysis of the miRNAs that target key genes involved in myristoylation (NMT1,
      NMT2, MetAP2), we have narrowed down a list of promising candidates for further
      analysis. Our condensed panel of miRNAs identifies 35 miRNAs linked to cancer, 21
      miRNAs linked to developmental and immune signaling pathways, and 14 miRNAs
      linked to infectious disease (primarily HIV). The miRNAs panel that was analyzed
      revealed several NMT-targeting mRNAs (messenger RNA) that are implicated in
      diseases associated with NMT signaling alteration, providing a link between the
      realms of miRNA and myristoylation signaling. These findings verify miRNA as an
      additional facet of myristoylation signaling that must be considered to gain a
      full perspective. This study provides the groundwork for future studies
      concerning NMT-transcript-binding miRNAs, and will potentially lead to the
      development of new diagnostic/prognostic biomarkers and therapeutic targets for
      several important diseases.

PMID- 29579065
TI  - The effect of estrogenic compounds on psychosis-like behaviour in female rats.
AB  - 17beta-estradiol treatment has shown benefit against schizophrenia symptoms,
      however long-term use may be associated with negative side-effects. Selective
      estrogen receptor modulators, such as raloxifene and tamoxifen, have been
      proposed as suitable alternatives to 17beta-estradiol. An isomer of 17beta
      estradiol, 17alpha-estradiol, is considered less carcinogenic, and non-feminising
      in males, however little is known about its potential as a treatment for
      schizophrenia. Moreover, the mechanism underlying the therapeutic action of
      estrogens remains unclear. We aimed to investigate the ability of these
      estrogenic compounds to attenuate psychosis-like behaviour in rats. We used two
      acute pharmacologically-induced assays of psychosis-like behaviour:
      psychotomimetic drug-induced hyperlocomotion and disruption of prepulse
      inhibition (PPI). Female Long Evans rats were either intact, ovariectomised
      (OVX), or OVX and chronically treated with 17beta-estradiol, 17alpha-estradiol,
      raloxifene or tamoxifen. Only 17beta-estradiol treatment attenuated locomotor
      hyperactivity induced by the indirect dopamine receptor agonist, methamphetamine.
      17beta-estradiol- and tamoxifen-treated rats showed attenuated methamphetamine-
      and apomorphine (dopamine D1/D2 receptor agonist)-induced disruption of PPI.
      Raloxifene-treated rats showed attenuated apomorphine-induced PPI disruption
      only. Baseline PPI was significantly reduced following OVX, and this deficit was
      reversed by all estrogenic compounds. Further, PPI in OVX rats was increased
      following administration of apomorphine. This study confirms a protective effect
      of 17beta-estradiol in two established animal models of psychosis, while
      tamoxifen showed beneficial effects against PPI disruption. In contrast, 17alpha
      estradiol and raloxifene showed little effect on dopamine receptor-mediated
      psychosis-like behaviours. This study highlights the utility of some estrogenic
      compounds to attenuate psychosis-like behaviour in rats, supporting the notion
      that estrogens have therapeutic potential for psychotic disorders.

PMID- 29579066
TI  - Assessment of viral methylation levels for high risk HPV types by newly designed
      consensus primers PCR and pyrosequencing.
AB  - BACKGROUND: Measuring viral DNA methylation in human papillomavirus (HPV)
      infected women showed promise for accurate detection of high-grade cervical
      lesions and cancer. Methylation status has been widely investigated for HPV16,
      sporadically for other HPV types. METHODS: Objective of this methodological study
      was to set up molecular methods to test the methylation levels in the twelve
      oncogenic HPV types by pyrosequencing, minimizing the number of HPV type-specific
      PCR protocols. Target CpGs were selected on the HPV L1 (two regions, L1 I and L1
      II) and L2 genes. Study samples included DNA stored at Turin, Italy, purified by
      cervical cells collected in Standard Transport Medium or PreservCyt from women
      who participated in two studies (N = 126 and 140) nested within the regional
      organized screening programme. PCR consensus primers were designed by PyroMark
      Assay Design software to be suitable for amplification of many different
      oncogenic HPV types. RESULTS: Generation of consensus primers was successful for
      L1 I and II regions, unsuccessful for L2 region, for which HPV type-specific
      primers remained necessary. The difference between replicated tests on the same
      sample was <=4% in 88%, 77% and 91% of cases when targeting the L1 I, L1 II and
      L2 regions, respectively. The corresponding intra-class correlation coefficients
      (ICC) were 0.94, 0.87 and 0.97 respectively. When comparing methylation measures
      based on consensus and type-specific primers, ICC was 0.97 for the L1 I region
      and 0.99 the for L1 II region. CONCLUSIONS: The proposed protocols, applying
      consensus primers suitable to amplify the oncogenic HPV types and minimize the
      number of PCR reactions, represent a promising tool to quantify viral methylation
      in women positive for any high risk HPV type. IMPACT: Potential application of
      these methylation protocols in screening settings can be explored to identify
      women with high probability of progression to high grade lesions.

PMID- 29579067
TI  - Audio-based performance evaluation of squash players.
AB  - In competitive sports it is often very hard to quantify the performance. A player
      to score or overtake may depend on only millesimal of seconds or millimeters. In
      racquet sports like tennis, table tennis and squash many events will occur in a
      short time duration, whose recording and analysis can help reveal the differences
      in performance. In this paper we show that it is possible to architect a
      framework that utilizes the characteristic sound patterns to precisely classify
      the types of and localize the positions of these events. From these basic
      information the shot types and the ball speed along the trajectories can be
      estimated. Comparing these estimates with the optimal speed and target the
      precision of the shot can be defined. The detailed shot statistics and precision
      information significantly enriches and improves data available today. Feeding
      them back to the players and the coaches facilitates to describe playing
      performance objectively and to improve strategy skills. The framework is
      implemented, its hardware and software components are installed and tested in a
      squash court.

PMID- 29579068
TI  - Rapid activity-dependent modulation of the intrinsic excitability through up
      regulation of KCNQ/Kv7 channel function in neonatal spinal motoneurons.
AB  - Activity-dependent changes in the properties of the motor system underlie the
      necessary adjustments in its responsiveness on the basis of the environmental and
      developmental demands of the organism. Although plastic changes in the properties
      of the spinal cord have historically been neglected because of the archaic belief
      that the spinal cord is constituted by a hardwired network that simply relays
      information to muscles, plenty of evidence has been accumulated showing that
      synapses impinging on spinal motoneurons undergo short- and long-term plasticity.
      In the brain, brief changes in the activity level of the network have been shown
      to be paralleled by changes in the intrinsic excitability of the neurons and are
      suggested to either reinforce or stabilize the changes at the synaptic level.
      However, rapid activity-dependent changes in the intrinsic properties of spinal
      motoneurons have never been reported. In this study, we show that in neonatal
      mice the intrinsic excitability of spinal motoneurons is depressed after
      relatively brief but sustained changes in the spinal cord network activity. Using
      electrophysiological techniques together with specific pharmacological blockers
      of KCNQ/Kv7 channels, we demonstrate their involvement in the reduction of the
      intrinsic excitability of spinal motoneurons. This action results from an
      increased M-current, the product of the activation of KCNQ/Kv7 channels, which
      leads to a hyperpolarization of the resting membrane potential and a decrease in
      the input resistance of spinal motoneurons. Computer simulations showed that
      specific up-regulations in KCNQ/Kv7 channels functions lead to a modulation of
      the intrinsic excitability of spinal motoneurons as observed experimentally.
      These results indicate that KCNQ/Kv7 channels play a fundamental role in the
      activity-dependent modulation of the excitability of spinal motoneurons.

PMID- 29579070
TI  - Encountering epidemic effects of leaf spot disease (Alternaria brassicae) on Aloe
      vera by fungal biocontrol agents in agrifields-An ecofriendly approach.
AB  - Aloe vera (L.) Burm.f. is a highly important and extensively cultivated medicinal
      plant and that is also extensively used in the cosmetic industry. It has been
      frequently reported to suffer from Alternaria leaf spot disease in various parts
      of the world. Various fungicides used to combat this disease, have deleterious
      effects on the environment and on pharmacologically important constituents of
      Aloe vera. To avoid the harmful effects of fungicides an ecofriendly approach has
      been adopted here. A weekly survey was conducted during 2013-2015 in and around
      North 24 Parganas (West Bengal) to obtain the percentage of disease index (PDI).
      For biological control of the disease, screening of the antagonistic efficacy of
      biocontrol agents was carried out through the in vitro dual-culture-plate method
      and scanning electron microscopy (SEM) was used to study the mechanism. The in
      vitro effects of fungicides on the radial growth of the pathogen were evaluated
      through the poison food method and were compared with potent antagonistic fungi.
      Field application of potent antagonistic fungi was conducted through the dip-and
      spray method. The results showed that, the PDI peaked during the hot and humid
      conditions of May to September (76.57%-98.57%) but decreased during the winter,
      December-January (35.71-46.66%). Trichoderma asperellum exerted the greatest
      inhibition of the radial growth of A. brassicae acting through non volatile
      (70.39%) and volatile metabolites (72.17%). A SEM study confirmed the
      hyperparasitic nature of T. asperellum through hyphal coiling-T. asperellum was
      similar to 2% blitox-50 (73.92%) and better than 2% bavistin (59.77%) (in vitro).
      In agricultural field trials (2013-15), Trichoderma application restricted the
      disease to the smallest area (PDI 24.00-29.33%) in comparison to untreated plots
      (73.33%). In conclusion, saplings treated with the dip method (108 spores / mL)
      and sprayed 4 times with a spore suspension of biocontrol agents such as T.
      asperellum, T. viride and T. harzianum, standardized at a rate of 2.5 L / plot
      (36 sq ft) (108 spores/ mL) are suggested for the ecofriendly management of this
      epidemic leaf spot disease of Aloe vera in agricultural fields.

PMID- 29579069
TI  - Molecular and morphological data of the freshwater fish Glandulocauda
      melanopleura (Characiformes: Characidae) provide evidences of river captures and
      local differentiation in the Brazilian Atlantic Forest.
AB  - The current distribution of freshwater fishes across multiple basins along
      Eastern Brazil can be associated to two main events: river captures or temporary
      paleoconnections. Apparently, river captures had a more significant role on
      distribution and structuring of species from upland areas, such as Glandulocauda
      melanopleura. Populations of this species are found in contiguous drainages in
      presently isolated upper parts of Rio Tiete and the coastal basins of Guaratuba,
      Itatinga, Itanhaem, and Ribeira de Iguape, in the Atlantic Forest domain. The
      allopatric and disjoint distribution of G. melanopleura associated with variation
      of morphological characters detected among geographically isolated populations
      stimulated this study. Thus, an integrative approach was undertaken, including
      morphological and molecular data, to better understand the evolutionary history
      of the species and the area where it occurs. Molecular analyses based on two
      mitochondrial markers revealed a strong genetic structure within G. melanopleura,
      that allowed recognition of two lineages, one distributed in both the upper Tiete
      and Itanhaem and the other in the Guaratuba. Overall, morphological data revealed
      some intraspecific overlapping variation, indicating that all samples are
      conspecific. Phylogenetic and phylogeographic analyses allied to divergence times
      and geomorphological information indicate that the current distribution of G.
      melanopleura is a result of relatively recent river captures involving the Tiete
      and some other coastal drainages. Although of recent origin, they occurred long
      enough to completely isolate these populations, since there are no haplotypes
      sharing between them. The conservation status of this species is also discussed,
      and our results corroborate the need to understand population structure for
      conservation planning.

PMID- 29579071
TI  - HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of
      superfamily protein sequences with a reliable cut-off threshold.
AB  - BACKGROUND: Protein superfamilies can be divided into subfamilies of proteins
      with different functional characteristics. Their sequences can be classified
      hierarchically, which is part of sequence function assignation. Typically, there
      are no clear subfamily hallmarks that would allow pattern-based function
      assignation by which this task is mostly achieved based on the similarity
      principle. This is hampered by the lack of a score cut-off that is both sensitive
      and specific. RESULTS: HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable
      cut-off threshold to the popular HMMER. Using a high quality superfamily
      phylogeny, it clusters a set of training sequences such that the cluster-specific
      HMMER profiles show cluster or subfamily member detection with 100% precision and
      recall (P&R), thereby generating a specific threshold as inclusion cut-off.
      Profiles and thresholds are then used as classifiers to screen a target dataset.
      Iterative inclusion of novel sequences to groups and the corresponding HMMER
      profiles results in high sensitivity while specificity is maintained by imposing
      100% P&R self detection. In three presented case studies of protein
      superfamilies, classification of large datasets with 100% precision was achieved
      with over 95% recall. Limits and caveats are presented and explained.
      CONCLUSIONS: HMMERCTTER is a promising protein superfamily sequence classifier
      provided high quality training datasets are used. It provides a decision support
      system that aids in the difficult task of sequence function assignation in the
      twilight zone of sequence similarity. All relevant data and source codes are
      available from the Github repository at the following URL:
      https://github.com/BBCMdP/HMMERCTTER.

PMID- 29579072
TI  - Judgement analysis of case severity and future risk of disability regarding
      chronic low back pain by general practitioners in Ireland.
AB  - Chronic low back pain is a major healthcare burden that has wide ranging effects
      on the individual, their family, society and the workplace. However, appropriate
      management and treatment is often difficult, as a majority of cases are non
      specific in terms of underlying pathology. As a result, there are extensive
      differences in both individual patient preferences for treatment and treatment
      decisions amongst general practitioners. The current study examined the clinical
      judgements of GPs in Ireland, regarding fictional patients' case severity and
      future risk of disability, through judgement analysis. Judgement analysis (JA) is
      an idiographic regression modelling technique that has been utilised in extant
      healthcare research for the purpose of allocating weighting to judgement
      criteria, or cues, observed by professionals in their clinical decision-making.
      The primary aim of the study was to model two critical information utilisation
      tasks performed by GPs with regard to CLBP-in combining information cues to form
      a judgement about current case severity and a judgement about the same patient's
      risk of future disability. It was hypothesised that the judgement weighting would
      differ across the two judgements and that judgements regarding future risk of
      disability would be less consistent among GPs than judgements about case
      severity. Results from the regression-based judgement analysis and subsequent
      follow-up statistical analysis provided support for both study hypotheses. Study
      findings are discussed in light of theory and research on judgement, clinical
      decision-making and chronic low back pain.

PMID- 29579073
TI  - The impact of methadone maintenance therapy on access to regular physician care
      regarding hepatitis C among people who inject drugs.
AB  - BACKGROUND & AIMS: People who inject drugs (PWID) living with hepatitis C virus
      (HCV) infection often experience barriers to accessing HCV treatment and care.
      New, safer and more effective direct-acting antiviral-based therapies offer an
      opportunity to scale-up HCV-related services. Methadone maintenance therapy (MMT)
      programs have been shown to be effective in linking PWID to health and support
      services, largely in the context of HIV. The objective of the study was to
      examine the relationship between being enrolled in MMT and having access to
      regular physician care regarding HCV among HCV antibody-positive PWID in
      Vancouver, Canada. DESIGN: Three prospective cohort studies of people who use
      illicit drugs. SETTING: Vancouver, Canada. PARTICIPANTS: We restricted the study
      sample to 1627 HCV-positive PWID between September 2005 and May 2015.
      MEASUREMENTS: A marginal structural model using inverse probability of treatment
      weights was used to estimate the longitudinal relationship between being enrolled
      in MMT and having a regular HCV physician and/or specialist. FINDINGS: In total,
      1357 (83.4%) reported having access to regular physician care regarding HCV at
      least once during the study period. A marginal structural model estimated a 2.12
      (95% confidence interval [CI]: 1.77-2.20) greater odds of having a regular HCV
      physician among participants enrolled in MMT compared to those not enrolled.
      CONCLUSIONS: HCV-positive PWID who enrolled in MMT were more likely to report
      access to regular physician care regarding HCV compared to those not enrolled in
      MMT. These findings demonstrate that opioid agonist treatment may be helpful in
      linking PWID to HCV care, and highlight the need to better engage people who use
      drugs in substance use care, when appropriate.

PMID- 29579074
TI  - Prevalence and determinants of self-medication practice among selected households
      in Addis Ababa community.
AB  - BACKGROUND AND AIM: Self-medication (SM) is one part of self-care which is known
      to contribute to primary health care. If practiced appropriately, it has major
      benefits for the consumers such as self-reliance and decreased expense. However,
      inappropriate practice can have potential dangers such as incorrect self
      diagnosis, dangerous drug-drug interactions, incorrect manner of administration,
      incorrect dosage, incorrect choice of therapy, masking of a severe disease,
      and/or risk of dependence and abuse. The main objective of this study was to
      assess the prevalence and determinants of the self-medication practice (SMP) in
      Addis Ababa. METHODOLOGY: A community based cross-sectional study was conducted
      among selected households in Addis Ababa from April 2016 to May 2016, with a
      recall period of two months before its conduction. Trained data collectors were
      employed to collect the data from the 604 sampled participants using pre-tested
      and validated questionnaires. RESULT: Among the 604 participants involved in this
      study, 422 (69.9%) were female and 182 (30.1%) were male and there was a mean age
      of 41.04 (+/- 13.45) years. The prevalence of SM in this study was 75.5%. The
      three most frequently reported ailments were headache 117 (25.7%), abdominal pain
      59 (12.9%) and cough 54 (11.8%). The two main reasons for SM were mildness of
      illness 216 (47.4%) and previous knowledge about the drug 106 (23.2%). The two
      most frequently consumed medications were paracetamol 92 (20.2%) and traditional
      remedies 73 (16.0%), while drug retail outlets 319 (83.3%) were the main source
      of drugs. The two most frequently reported source of drug information were health
      professionals 174 (45.4%) and experience from previous treatment 82 (21.4%).
      Moreover, there were statistically significant differences among respondents who
      reported practicing SM based on income and knowledge about appropriate SMP.
      CONCLUSION AND RECOMMENDATION: Self-medication was practiced with a range of
      drugs from the conventional paracetamol and NSAIDs to antimicrobials. Being that
      the practice of SM is inevitable, health authorities and professionals are highly
      demanded to educate the public not only on the advantages and disadvantages of SM
      but on its proper use.

PMID- 29579075
TI  - Effects of pharmacologic sclerostin inhibition or testosterone administration on
      soleus muscle atrophy in rodents after spinal cord injury.
AB  - Sclerostin is a circulating osteocyte-derived glycoprotein that negatively
      regulates Wnt-signaling after binding the LRP5/LRP6 co-receptors. Pharmacologic
      sclerostin inhibition produces bone anabolic effects after spinal cord injury
      (SCI), however, the effects of sclerostin-antibody (Scl-Ab) on muscle morphology
      remain unknown. In comparison, androgen administration produces bone
      antiresorptive effects after SCI and some, but not all, studies have reported
      that testosterone treatment ameliorates skeletal muscle atrophy in this context.
      Our purposes were to determine whether Scl-Ab prevents hindlimb muscle loss after
      SCI and compare the effects of Scl-Ab to testosterone enanthate (TE), an agent
      with known myotrophic effects. Male Sprague-Dawley rats aged 5 months received:
      (A) SHAM surgery (T8 laminectomy), (B) moderate-severe contusion SCI, (C) SCI+TE
      (7.0 mg/wk, im), or (D) SCI+Scl-Ab (25 mg/kg, twice weekly, sc). Twenty-one days
      post-injury, SCI animals exhibited a 31% lower soleus mass in comparison to SHAM,
      accompanied by >50% lower soleus muscle fiber cross-sectional area (fCSA) (p<0.01
      for all fiber types). Scl-Ab did not prevent soleus atrophy, consistent with the
      relatively low circulating sclerostin concentrations and with the 91-99% lower
      LRP5/LRP6 gene expressions in soleus versus tibia (p<0.001), a tissue with known
      anabolic responsiveness to Scl-Ab. In comparison, TE partially prevented soleus
      atrophy and increased levator ani/bulbocavernosus (LABC) mass by 30-40% (p<0.001
      vs all groups). The differing myotrophic responsiveness coincided with a 3-fold
      higher androgen receptor gene expression in LABC versus soleus (p<0.01). This
      study provides the first direct evidence that Scl-Ab does not prevent soleus
      muscle atrophy in rodents after SCI and suggests that variable myotrophic
      responses in rodent muscles after androgen administration are influenced by
      androgen receptor expression.

PMID- 29579076
TI  - Genetic structure of wild pea (Pisum sativum subsp. elatius) populations in the
      northern part of the Fertile Crescent reflects moderate cross-pollination and
      strong effect of geographic but not environmental distance.
AB  - Knowledge of current genetic diversity and mating systems of crop wild relatives
      (CWR) in the Fertile Crescent is important in crop genetic improvement, because
      western agriculture began in the area after the cold-dry period known as Younger
      Dryas about 12,000 years ago and these species are also wild genepools of the
      world's most important food crops. Wild pea (Pisum sativum subsp. elatius) is an
      important source of genetic diversity for further pea crop improvement harbouring
      traits useful in climate change context. The genetic structure was assessed on
      187 individuals of Pisum sativum subsp. elatius from fourteen populations
      collected in the northern part of the Fertile Crescent using 18,397 genome wide
      single nucleotide polymorphism DARTseq markers. AMOVA showed that 63% of the
      allelic variation was distributed between populations and 19% between individuals
      within populations. Four populations were found to contain admixed individuals.
      The observed heterozygosity ranged between 0.99 to 6.26% with estimated self
      pollination rate between 47 to 90%. Genetic distances of wild pea populations
      were correlated with geographic but not environmental (climatic) distances and
      support a mixed mating system with predominant self-pollination. Niche modelling
      with future climatic projections showed a local decline in habitats suitable for
      wild pea, making a strong case for further collection and ex situ conservation.

PMID- 29579077
TI  - Simulated tri-trophic networks reveal complex relationships between species
      diversity and interaction diversity.
AB  - Most of earth's biodiversity is comprised of interactions among species, yet it
      is unclear what causes variation in interaction diversity across space and time.
      We define interaction diversity as the richness and relative abundance of
      interactions linking species together at scales from localized, measurable webs
      to entire ecosystems. Large-scale patterns suggest that two basic components of
      interaction diversity differ substantially and predictably between different
      ecosystems: overall taxonomic diversity and host specificity of consumers.
      Understanding how these factors influence interaction diversity, and quantifying
      the causes and effects of variation in interaction diversity are important goals
      for community ecology. While previous studies have examined the effects of
      sampling bias and consumer specialization on determining patterns of ecological
      networks, these studies were restricted to two trophic levels and did not
      incorporate realistic variation in species diversity and consumer diet breadth.
      Here, we developed a food web model to generate tri-trophic ecological networks,
      and evaluated specific hypotheses about how the diversity of trophic interactions
      and species diversity are related under different scenarios of species richness,
      taxonomic abundance, and consumer diet breadth. We investigated the accumulation
      of species and interactions and found that interactions accumulate more quickly;
      thus, the accumulation of novel interactions may require less sampling effort
      than sampling species in order to get reliable estimates of either type of
      diversity. Mean consumer diet breadth influenced the correlation between species
      and interaction diversity significantly more than variation in both species
      richness and taxonomic abundance. However, this effect of diet breadth on
      interaction diversity is conditional on the number of observed interactions
      included in the models. The results presented here will help develop realistic
      predictions of the relationships between consumer diet breadth, interaction
      diversity, and species diversity within multi-trophic communities, which is
      critical for the conservation of biodiversity in this period of accelerated
      global change.

PMID- 29579078
TI  - A novel high-throughput immunofluorescence analysis method for quantifying
      dystrophin intensity in entire transverse sections of Duchenne muscular dystrophy
      muscle biopsy samples.
AB  - Clinical trials using strategies aimed at inducing dystrophin expression in
      Duchenne muscular dystrophy (DMD) are underway or at advanced planning stage,
      including splice switching antisense oligonucleotides (AON), drugs to induce read
      through of nonsense mutations and viral mediated gene therapy. In all these
      strategies, different dystrophin proteins, often internally deleted, are
      produced, similar to those found in patients with the milder DMD allelic variant,
      Becker muscular dystrophy (BMD). The primary biological endpoint of these trials
      is to induce functional dystrophin expression. A reliable and reproducible method
      for quantification of dystrophin protein expression at the sarcolemma is crucial
      to monitor the biochemical outcome of such treatments. We developed a new high
      throughput semi quantitative fluorescent immunofluorescence method for
      quantifying dystrophin expression in transverse sections of skeletal muscle. This
      technique is completely operator independent as it based on an automated scanning
      system and an image processing script developed with Definiens software. We
      applied this new acquisition-analysis method to quantify dystrophin and
      sarcolemma-related proteins using paediatric control muscles from cases without a
      neuromuscular disorder as well as DMD and BMD samples. The image analysis script
      was instructed to recognize myofibres immunostained for spectrin or laminin while
      dystrophin was quantified in each identified myofibre (from 2,000 to over 20,000
      fibres, depending on the size of the biopsy). We were able to simultaneously
      extrapolate relevant parameters such as mean sarcolemmal dystrophin, mean
      spectrin and laminin intensity, fibre area and diameter. In this way we assessed
      dystrophin production in each muscle fibre in samples of DMD, BMD and controls.
      This new method allows the unbiased quantification of dystrophin in every
      myofibre within a transverse muscle section and will be of help for translational
      research projects as a biological outcome in clinical trials in DMD and BMD.

PMID- 29579079
TI  - Enhanced differentiation of human pluripotent stem cells into cardiomyocytes by
      bacteria-mediated transcription factors delivery.
AB  - Virus-mediated expression of defined transcription factor (TF) genes can
      effectively induce cellular reprogramming. However, sustained expression of the
      TFs often hinders pluripotent stem cell (PSC) differentiation into specific cell
      types, as each TF exerts its effect on PSCs for a defined period of time during
      differentiation. Here, we applied a bacterial type III secretion system (T3SS)
      based protein delivery tool to directly translocate TFs in the form of protein
      into human PSCs. This transient protein delivery technique showed high delivery
      efficiency for hPSCs, and it avoids potential genetic alterations caused by the
      introduction of transgenes. In an established cardiomyocyte de novo
      differentiation procedure, five transcriptional factors, namely GATA4, MEF2C,
      TBX5, ESRRG and MESP1 (abbreviated as GMTEM), were translocated at various time
      points. By detecting the expression of cardiac marker genes (Nkx2.5 and cTnT), we
      found that GMTEM proteins delivered on mesoderm stage of the cardiomyocytes
      lineage differentiation significantly enhanced both the human ESC and iPSC
      differentiation into cardiomyocytes, while earlier or later delivery diminished
      the enhancing effect. Furthermore, all of the five factors were required to
      enhance the cardiac differentiation. This work provides a virus-free strategy of
      transient transcription factors delivery for directing human stem cell fate
      without jeopardizing genome integrity, thus safe for biomedical applications.

PMID- 29579080
TI  - Variation in the microbiome of the urogenital tract of Chlamydia-free female
      koalas (Phascolarctos cinereus) with and without 'wet bottom'.
AB  - Koalas (Phascolarctos cinereus) are iconic Australian marsupials currently
      threatened by several processes, including infectious diseases and ecological
      disruption. Infection with Chlamydia pecorum, is considered a key driver of
      population decline. The clinical sign of 'wet bottom', a staining of the rump
      associated with urinary incontinence, is often caused by chlamydial urinary tract
      infections. However, wet bottom has been recorded in koalas free of C. pecorum,
      suggesting other causative agents in those individuals. We used 16S rRNA
      diversity profiling to investigate the microbiome of the urogenital tract of ten
      female koalas in order to identify potential causative agents of wet bottom,
      other than C. pecorum. Five urogenital samples were processed from koalas
      presenting with wet bottom and five were clinically normal. All koalas were
      negative for C. pecorum infection. We detected thirteen phyla across the ten
      samples, with Firmicutes occurring at the highest relative abundance (77.6%). The
      order Lactobacillales, within the Firmicutes, comprised 70.3% of the reads from
      all samples. After normalising reads using DESeq2 and testing for significant
      differences (P < 0.05), there were 25 operational taxonomic units (OTUs) more
      commonly found in one group over the other. The families Aerococcaceae and
      Tissierellaceae both had four significantly differentially abundant OTUs. These
      four Tissierellaceae OTUs were all significantly more abundant in koalas with wet
      bottom. This study provides the foundation for future investigations of causes of
      koala wet bottom, other than C. pecorum infection. This is of clinical relevance
      as wet bottom is often assumed to be caused by C. pecorum and treated
      accordingly. Our research highlights that other organisms may be causing wet
      bottom, and these potential aetiological agents need to be further investigated
      to fully address the problems this species faces.

PMID- 29579081
TI  - Genetics in TNF-TNFR pathway: A complex network causing spondyloarthritis and
      conditioning response to anti-TNFalpha therapy.
AB  - OBJECTIVES: We investigated whether polymorphisms (SNPs) in the promoter region
      of TNFA, or in the autoinflammatory TNFRSF1A and MEFV genes, concur with HLA-B27
      in enhancing the risk of Spondyloarthritis (SpA) and/or in predicting the
      response to anti-TNFalpha treatment. METHODS: 373 controls and 137 SpA (82 with
      Psoriatic Arthritis-PsA and 55 with Ankylosing Spondylitis- AS; 98/137 under
      TNFalpha inhibitor therapy) from the Veneto Region (Italy) were studied. TNFA
      polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) and HLA-B27 were assayed
      by RT-PCR. Direct sequencing of MEFV (exons 2,3,5 and 10) and TNFRSF1A (exons
      2,3,4 and 6) genes were performed. RESULTS: HLA-B27 was associated with AS (chi2
      = 120.1; p = 0.000). Only the TNFA -1031T>C was singly associated with SpA, and
      the haplotype C/G, resulting from -1031T>C/-308G>A combination, was significantly
      associated with a reduced risk of SpA (OR: 0.67, CI: 0.46-0.97; p = 0.035). Two
      SNPs were identified in TNFRSF1A, the R92Q (Minor allele frequency-MAF = 0.034)
      and c.625+10A>G (MAF = 0.479). None of them was associated with SpA (p>0.05). The
      TNFRSF1A c.625+10 G allele was associated with late response to anti-TNFalpha
      therapy (p = 0.031). Twenty-one SNPs were identified in MEFV gene, 10 with a
      known potential functional significance. Variant alleles were extremely rare in
      our population (MAF<0.025) except for R202Q (MAF = 0.27). None was associated
      with SpA diagnosis (p>0.05). CONCLUSION: TNFRSF1A and MEFV gene SNPs are not
      associated with SpA in the North-East of Italy. AS risk appears to depend not
      only on HLA-B27, but also on the protective TNFA haplotype -1031C/-308G. The
      TNFRSF1A c.625+10A>G impacts on the response to anti-TNFalpha therapy.

PMID- 29579082
TI  - PrePex circumcision surveillance: Adverse events and analgesia for device
      removal.
AB  - BACKGROUND: The PrePex medical male circumcision (MMC) device is relatively easy
      to place and remove with some training. PrePex has been evaluated in several
      countries to assess feasibility and acceptability. However, several studies have
      reported pain associated with removal. OBJECTIVE: To assess safety of PrePex and
      whether analgesia administered prior to removal reduces pain experienced by
      participants. METHODS: A multi-site non-randomized, prospective cohort study in
      which adult (18-45 years old) males requesting PrePex device male circumcision,
      were enrolled in six South African clinics from July 2014 to March 2015.
      Participants were routinely provided with analgesia shortly after the
      surveillance commenced following a protocol review. Analgesia regimen for device
      removal depended on medication availability at clinics. RESULTS: Of 1023 enrolled
      participants who had PrePex placed, 98% (1004) had the device removed at a study
      clinic. Their median age was 25 (IQR: 21-30) years. HIV sero-positivity was 3.6%
      (37/1023). Nurses placed and removed half of all devices. Adverse events were
      experienced by 2.4% (25/1023) of participants; 15 required surgical intervention:
      device displacement (5/14), early removals (3/14), self-removals (5/14) and
      insufficient skin removed (2/14). Majority (792: 79%) of participants received
      analgesia. Most received either paracetamol-codeine (33%), lidocaine (29%) or
      EMLA and Oral Combination (28%). A lower proportion of participants who received
      any analgesia (except for lidocaine) prior to PrePex removal experienced severe
      pain compared to those who received no analgesia (16.6% vs. 29%: p = 0.0001).
      CONCLUSION: Reported adverse events during this PrePex active surveillance were
      similar to previous reports and to those of surgical circumcision. Pain
      medication provided prior to removal is effective at decreasing severe pain
      during PrePex device removal.

PMID- 29579083
TI  - Obesity and emergency care in the French CONSTANCES cohort.
AB  - CONTEXT: Obese patients are raising specific questions in emergency care such as
      equipment issues or urgent procedures. Even though obesity prevalence and
      subsequent health expenditure are increasing worldwide, there is scarce
      literature about their specific resource utilization of Emergency Departments
      (ED). These few studies do not take into account both socio-economic situation
      and comorbidities which are well-known factors influencing healthcare use. Our
      objective was to assess the emergency care resource utilization of obese
      individuals (Body Mass Index (BMI) >= 30kg.m-2) compared to normal-weight
      individuals taking into account comorbidities and social-economic situations.
      METHODS: The French CONSTANCES epidemiologic cohort is a randomly selected sample
      of French adults. Participants data are linked to the National Health Insurance
      Database collecting all medical acts. The rate of ED visits of obese (and each
      obesity class) and normal-weight participants were compared considering
      confounding factors (comorbidities, various socio-economic data). The primary
      endpoint was to have visited the ED between 2010 and 2013. Sex-separated analysis
      and multivariate logistic regression models were performed and adjusted odds
      ratios [OR] (95% Confidence Intervals [CI]) were calculated. RESULTS: We included
      21,035 normal-weight and 5,003 obese participants. Obese participants visited the
      ED more often than normal-weight participants (men: 30.5% vs. 26.7%; women: 30.3%
      vs. 24.4%, P<0.001). Obese participants presented more comorbidities and a lower
      socio-economic situation than normal-weight participants. After adjustment, obese
      participants had a higher risk of visiting ED (men: OR = 1.18; 95% CI: 1.04-1.33;
      and women: OR = 1.36; 95% CI: 1.22-1.52), with a higher risk for class III
      participants (BMI >= 40 kg.m-2) (men: OR = 2.18; CI 95%: 1.32-3.63; and women: OR
      = 1.85; 95% CI: 1.38-2.49). CONCLUSION: Obese individuals have a higher level of
      emergency care resource utilization than normal-weight individuals and it
      increases with severe obesity. Further studies are needed to better understand
      their healthcare pathways leading to EDs.

PMID- 29579085
TI  - A performance-based evaluation of chemically similar (carbonate) tempers from
      Late Prehistoric (AD 1200-1700) Ohio: Implications for human selection and
      production of ceramic technology.
AB  - PURPOSE: This study was designed to assess the mechanical properties of two
      calcium carbonate tempers, limestone and burnt shell. These tempers have been
      previously compared, in separate studies, to silicate-based grit or sand temper
      and, relative to the latter, are assumed to possess similar mechanical
      properties. However, their simultaneous use at the Morrison Village site begs the
      question: do these two calcium carbonate tempers indeed possess similar
      mechanical properties? In order to assess their performance characteristics, a
      side-by-side controlled experimental test was conducted to determine the degree
      of similarity in providing increased vessel strength and toughness. METHODS:
      Standardized ceramic test samples were systematically prepared via a set,
      explicit protocol. An Instron Series IX universal testing machine configured with
      a four-point flexural test jig was used to perform a flexural strength test of
      the test samples. The Instron load and deflection data were used to calculate
      three values related to mechanical performance: peak load, modulus of rupture,
      and modulus of elasticity. RESULTS: All four comparative tests clearly show
      substantial differences in peak load, modulus of rupture, and modulus of
      elasticity. These differences are statistically significant for each performance
      attribute in every iteration of the experiment and as indicated by Mann-Whitney U
      Tests. CONCLUSIONS: These results do not support the hypothesis that limestone
      and burnt shell offer the same performance characteristics. These results have
      implications for our understanding of prehistoric human selection of temper and
      the evolution of ceramic technology. Although both carbonate-based tempers are
      currently thought to offer the same benefits during the initial phase of pottery
      production, their contrasting post firing properties would have provided distinct
      benefits in different contexts. Future assessments of the Morrison Village
      ceramic assemblage should focus on residue analysis, or other functional
      indicators, to support or falsify this hypothesis.

PMID- 29579084
TI  - Reliability and usefulness of spirometry performed during admission for COPD
      exacerbation.
AB  - OBJECTIVES: Although not currently recommended, spirometry during hospitalization
      due to exacerbation of chronic obstructive pulmonary disease (COPD) is an
      opportunity to enhance the diagnosis of this disease. The aim of the present
      study was to assess the usefulness and reliability of spirometry before hospital
      discharge, comparing it to measurements obtained during clinical stability.
      METHODS: This prospective longitudinal observational study compares spirometry
      results before and 8 weeks after discharge in consecutive patients admitted for
      COPD exacerbation. Concordance between results was assessed by the Kappa index,
      intraclass correlation coefficient, and Bland-Altman graphs. RESULTS: From an
      initial population of 179 COPD patients, 100 completed the study (mean age 67.8
      years, 83% men, 35% active smokers, FEV1 at clinical stability 40.3%). Forty-nine
      patients could not complete the study because they did not reach clinical
      stability. In three patients with obstructive spirometry during admission, the
      results were normal at follow-up. In the remaining patients, the COPD diagnosis
      was confirmed at stability with acceptable concordance. In 27 cases, spirometry
      improved more than 200 mL.No variables were found to be associated with this
      improvement or to explain it. CONCLUSIONS: This study provides information on the
      role of spirometry prior to hospital discharge in patients admitted for COPD
      exacerbation, demonstrating that it is a valid and reproducible method,
      representing an opportunity toimprove COPD diagnosis.

PMID- 29579086
TI  - Tuberculosis during pregnancy in the United States: Racial/ethnic disparities in
      pregnancy complications and in-hospital death.
AB  - BACKGROUND: Despite decades of efforts to eliminate tuberculosis (TB) in the
      United States (US), TB still contributes to adverse ill health, especially among
      racial/ethnic minorities. According to the Centers for Disease Control and
      Prevention, in 2016, about 87% of the TB cases reported in the US were among
      racial and ethnic minorities. The objective of this study is to explore the risks
      for pregnancy complications and in-hospital death among mothers diagnosed with TB
      across racial/ethnic groups in the US. METHODS: This retrospective cohort study
      utilized National Inpatient Sample data for all inpatient hospital discharges in
      the US. We analyzed pregnancy-related hospitalizations and births in the US from
      January 1, 2002 through December 31, 2014 (n = 57,393,459). Multivariable
      logistic regression was applied to generate odds ratios for the association
      between TB status and the primary study outcomes (i.e., pregnancy complications
      and in-hospital death) across racial/ethnic categories. RESULTS: The prevalence
      of TB was 7.1 per 100,000 pregnancy-related hospitalizations. The overall
      prevalence of pregnancy complications was 80% greater among TB-infected mothers
      than their uninfected counterparts. Severe pre-eclampsia, eclampsia, placenta
      previa, post-partum hemorrhage, sepsis and anemia occurred with greater frequency
      among mothers with a TB diagnosis than those without TB, irrespective of
      race/ethnicity. The rate of in-hospital death among TB patients was 37 times
      greater among TB-infected than in non-TB infected mothers (468.8 per 100,000
      versus 12.6 per 100,000). A 3-fold increased risk of in-hospital death was
      observed among black TB-negative mothers compared to their white counterparts. No
      racial/ethnic disparities in maternal morbidity or in-hospital death were found
      among mothers with TB disease. CONCLUSION: TB continues to be an important cause
      of morbidity and mortality among pregnant women in the US. Resources to address
      TB disease should also target pregnant women, especially racial/ethnic minorities
      who bear the greatest burden of the disease.

PMID- 29579088
TI  - The geography of references in elite articles: Which countries contribute to the
      archives of knowledge?
AB  - This study asks the question on which national "shoulders" the world's top-level
      research stands. Traditionally, the number of citations to national papers has
      been the evaluative measures of national scientific standings. We raise a
      different question: instead of analyzing the citations to a countries' articles
      (the forward view), we examine references to prior publications from specific
      countries cited in the most elite publications (the backward-citing-view). "Elite
      publications" are operationalized as the top-1% most-highly cited articles. Using
      the articles published from 2004 to 2013, we examine the research referenced in
      these works. Our results confirm the well-known fact that China has emerged to
      become a major player in science. However, China still belongs to the low
      contributors when countries are ranked as contributors to the cited references in
      top-1% articles. Using this perspective, the results do not support a decreasing
      trend for the USA; in fact, the USA exceeds expectations (compared to its
      publication share) in terms of references in the top-1% articles. Switzerland,
      Sweden, and the Netherlands also appear at the top of the list. However, the
      results for Germany are lower than statistically expected.

PMID- 29579087
TI  - Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE
      secretion.
AB  - Despite the important role of apolipoprotein E (apoE) secretion from astrocytes
      in brain lipid metabolism and the strong association of apoE4, one of the human
      apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD)
      little is known about the regulation of astrocytic apoE. Utilizing annotated
      chemical libraries and a phenotypic screening strategy that measured apoE
      secretion from a human astrocytoma cell line, inhibition of pan class I histone
      deacetylases (HDACs) was identified as a mechanism to increase apoE secretion.
      Knocking down select HDAC family members alone or in combination revealed that
      inhibition of the class I HDAC family was responsible for enhancing apoE
      secretion. Knocking down LXRalpha and LXRbeta genes revealed that the increase in
      astrocytic apoE in response to HDAC inhibition occurred via an LXR-independent
      pathway. Collectively, these data suggest that pan class I HDAC inhibition is a
      novel pathway for regulating astrocytic apoE secretion.

PMID- 29579089
TI  - To be understood: Transitioning to adult life for people with Autism Spectrum
      Disorder.
AB  - INTRODUCTION: The purpose of this study was to explore the viewpoints of parents
      of young people with Autism Spectrum Disorder (ASD) in relation to their child's
      transition to adulthood. METHODS: Data were collected during four structured
      focus groups with 19 parents of young people with ASD with average to high
      intellectual capacities. Condensed meaning units were identified and checked
      during focus groups, and were subsequently linked to the International
      Classification of Functioning, Disability and Health (ICF). RESULTS: Three major
      themes emerged: to be understood, to understand the world and to succeed. The ICF
      domains of activity and participation and environmental factors emerged as having
      the greatest potential to influence transition outcomes. CONCLUSIONS: Policies
      and services should focus on strengths to maximise participation in higher
      education, employment and independent living amongst young people with ASD.
      Interventions targeting environmental factors could be effective in improving
      participation in adult life. Person-centred and individualised approaches could
      further complement this approach supporting the transition to adulthood for
      people with ASD, ultimately improving outcomes in adulthood.

PMID- 29579090
TI  - Cytotoxic effects of four different root canal sealers on human osteoblasts.
AB  - The aim of this study was to evaluate the effect of an epoxy resin-based (AH
      Plus), a zinc oxide eugenol containing (Pulp-Canal-Sealer) and two calcium
      silicate containing (MTA-Fillapex and BioRoot-RCS) sealers on primary human
      osteoblasts (hOB) in freshly mixed and set state. All sealers were mixed strictly
      according to the manufacturers' instructions and identically samples were
      produced. In a pretest cytotoxic sealer concentrations were determined. Thus, for
      the main cell culture study, dilutions of sealer extract 1:1, 1:2, and 1:10 were
      used. To simulate a clinical scenario, extracts from freshly mixed sealer were
      added to the cells on day one. Extracts form set sealers were used for subsequent
      culturing for 24h, 7d, 14d, and 21d. Cell viability was analyzed by living-cell
      count, MTT-assay, and living/dead-staining, cytotoxicity by LDH-assay, and
      changes by Richardson-staining. All data were statistically evaluated by one way
      ANOVA and a posthoc analysis with Bonferroni-Holm testing (p<0.05). AH-Plus was
      cytotoxic in a freshly mixed state, but not when the sealer was set. MTA-Fillapex
      and Pulp-Canal-Sealer were cytotoxic in a fresh as well as in a set state.
      BioRoot-RCS showed the lowest toxicity in both states; where as a regeneration of
      the cells could be observed over time (p<0.05). Contact of freshly mixed AH-Plus
      to osteoblasts should be avoided. Pulp Canal Sealer and MTA-Fillapex showed no
      biocompatibility in contact with osteoblasts at all. BioRoot-RCS had a positive
      influence on the cell metabolism (bioactivity) and is biocompatible.

PMID- 29579091
TI  - Delay models for the early embryonic cell cycle oscillator.
AB  - Time delays are known to play a crucial role in generating biological
      oscillations. The early embryonic cell cycle in the frog Xenopus laevis is one
      such example. Although various mathematical models of this oscillating system
      exist, it is not clear how to best model the required time delay. Here, we study
      a simple cell cycle model that produces oscillations due to the presence of an
      ultrasensitive, time-delayed negative feedback loop. We implement the time delay
      in three qualitatively different ways, using a fixed time delay, a distribution
      of time delays, and a delay that is state-dependent. We analyze the dynamics in
      all cases, and we use experimental observations to interpret our results and put
      constraints on unknown parameters. In doing so, we find that different
      implementations of the time delay can have a large impact on the resulting
      oscillations.

PMID- 29579092
TI  - Comparison of gizzard and intestinal microbiota of wild neotropical birds.
AB  - Gut bacterial communities have been shown to be influenced by diet, host
      phylogeny and anatomy, but most of these studies have been done in captive
      animals. Here we compare the bacterial communities in the digestive tract of wild
      birds. We characterized the gizzard and intestinal microbiota among 8 wild
      Neotropical bird species, granivorous or frugivorous species of the orders
      Columbiformes and Passeriformes. We sequenced the V4 region of the 16S rRNA gene
      in 94 collected samples from 32 wild birds from 5 localities, and compared
      bacterial communities by foraging guild, organ, locality and bird taxonomy. 16S
      rRNA gene-based sequencing data were examined using QIIME with linear
      discriminant analysis effect size (LEfSe) and metabolic pathways were predicted
      using PICRUSt algorism. We identified 8 bacterial phyla, dominated by Firmicutes,
      Actinobacteria and Proteobacteria. Beta diversity analyses indicated significant
      separation of gut communities by bird orders (Columbiformes vs. Passerifomes) and
      between bird species (p<0.01). In lower intestine, PICRUSt shows a predominance
      of carbohydrate metabolism in granivorous birds and xenobiotics biodegradation
      pathways in frugivorous birds. Gizzard microbiota was significantly richer in
      granivorous, in relation to frugivorous birds (Chao 1; non-parametric t-test,
      p<0.05), suggesting a microbial gizzard function, beyond grinding food. The
      results suggest that the most important factor separating the bacterial community
      structure was bird taxonomy, followed by foraging guild. However, variation
      between localities is also likely to be important, but this could not been
      assessed with our study design.

PMID- 29579093
TI  - How much is too much?-Influence of X-ray dose on root growth of faba bean (Vicia
      faba) and barley (Hordeum vulgare).
AB  - X-ray CT is a powerful technology to study root growth in soil in-situ. Root
      systems can be studied in its true 3D geometry over time. Hence, the same plant
      can be scanned multiple times during development. A downside is the potential of
      X-rays to interfere with biological processes and therefore plant growth. The aim
      of this study is to evaluate the influence of cumulative X-ray dose on Vicia faba
      and Hordeum vulgare during a growth period of 17 days. One control treatment
      without X-ray scanning was compared to two treatments being scanned every two and
      four days, respectively. Scanned treatments received a maximum cumulative dose of
      less than 8 Gy. Plant species differed in their susceptibility to X-ray dose. For
      Vicia faba, mean total root length was reduced significantly. Leave growth was
      reduced as well. Number and length of second order laterals was reduced
      significantly, as well as length of first order laterals. Hordeum vulgare showed
      no negative impact of X-ray dose on any of the root parameters. Large differences
      between the two species investigated were detected in respect to susceptibility
      to X-ray dose. Results indicate that for X-ray CT studies involving temporal
      resolution a control treatment without scanning is required.

PMID- 29579094
TI  - Abdominal obesity is a common finding in normal and overweight subjects of Chile
      and is associated with increased frequency of cardiometabolic risk factors.
AB  - BACKGROUND/OBJECTIVES: Abdominal obesity (AO) is associated with elevated risk
      for cardiovascular diseases; however, this association is less clear for non
      obese people. We estimated the association of AO and cardiovascular risk factors
      (CVRF) and disease in non-obese adult individuals from Chile. SUBJECTS/METHODS:
      5248 adults (15 years of age or older) of both sexes from the Chilean National
      Health Survey (October 2009 -September 2010, response rate 85%.) were included.
      Information on myocardial infarction and stroke was self-reported. BMI, waist
      circumference (WC), arterial pressure, plasma glucose, and cholesterol levels
      were measured. Predictive accuracy of WC was evaluated by area under curve of
      receiver operating characteristic analysis and cut off points were established by
      Youden Index. Relationship between AO and CVRF was analyzed by Chi-squared tests.
      RESULTS: Normal weight/overweight/obesity were present in 34.4%/45.2%/18.1% of
      men and 33.4%/33.6%/27.5% of women. Predictive accuracy of WC to identify at
      least one CVRF was 0.70/0.67 and optimal cutoff points for WC in non-obese
      subjects were 91/83 cm in men/women, respectively. AO was present in 98.2%/99.1%
      of obese, 70.5%/77.4% of overweight and 12.4%/16.4% of normal weight men/women.
      AO was associated with increased frequency of CVRF in overweight men (6/8 and
      stroke) and women (4/8) and higher frequency in normal weight men (8/8 and
      myocardial infarction/stroke) and women (6/8 and myocardial infarction).
      CONCLUSIONS: WC cutoff points calculated for non-obese chilean population
      discriminate more differences in CVRF in normal weight woman. AO significantly
      increases the frequency of CVRF and diseases in overweight and especially normal
      weight individuals. WC can be used as a low cost, feasible and reproducible
      predictor for CVRF in non-obese individuals in most clinical settings.

PMID- 29579095
TI  - DNA strand-exchange patterns associated with double-strand break-induced and
      spontaneous mitotic crossovers in Saccharomyces cerevisiae.
AB  - Mitotic recombination can result in loss of heterozygosity and chromosomal
      rearrangements that shape genome structure and initiate human disease. Engineered
      double-strand breaks (DSBs) are a potent initiator of recombination, but whether
      spontaneous events initiate with the breakage of one or both DNA strands remains
      unclear. In the current study, a crossover (CO)-specific assay was used to
      compare heteroduplex DNA (hetDNA) profiles, which reflect strand exchange
      intermediates, associated with DSB-induced versus spontaneous events in yeast.
      Most DSB-induced CO products had the two-sided hetDNA predicted by the canonical
      DSB repair model, with a switch in hetDNA position from one product to the other
      at the position of the break. Approximately 40% of COs, however, had hetDNA on
      only one side of the initiating break. This anomaly can be explained by a
      modified model in which there is frequent processing of an early invasion (D
      loop) intermediate prior to extension of the invading end. Finally, hetDNA tracts
      exhibited complexities consistent with frequent expansion of the DSB into a gap,
      migration of strand-exchange junctions, and template switching during gap-filling
      reactions. hetDNA patterns in spontaneous COs isolated in either a wild-type
      background or in a background with elevated levels of reactive oxygen species
      (tsa1Delta mutant) were similar to those associated with the DSB-induced events,
      suggesting that DSBs are the major instigator of spontaneous mitotic
      recombination in yeast.

PMID- 29579096
TI  - Comparative pharmacokinetics and safety assessment of transdermal berberine and
      dihydroberberine.
AB  - The natural alkaloid berberine has been ascribed numerous health benefits
      including lipid and cholesterol reduction and improved insulin sensitivity in
      diabetics. However, oral (PO) administration of berberine is hindered by poor
      bioavailability and increasing dose often elicits gastro-intestinal side effects.
      To overcome the caveats associated with oral berberine, we developed transdermal
      (TD) formulations of berberine (BBR) and the berberine precursor dihydroberberine
      (DHB). These formulations were compared to oral BBR using pharmacokinetics,
      metabolism, and general safety studies in vivo. To complete this work, a
      sensitive quantitative LC-MS/MS method was developed and validated according the
      FDA guidelines for bioanalytical methods to simultaneously measure berberine,
      simvastatin, and simvastatin hydroxy acid with relative quantification used for
      the berberine metabolite demethylene berberine glucuronide (DBG). Acute
      pharmacokinetics in Sprague-Dawley rats demonstrated a statistically relevant
      ranking for berberine bioavailability based upon AUC0-8 as DHB TD > BBR TD >> BBR
      PO with similar ranking for the metabolite DBG, indicating that transdermal
      administration achieves BBR levels well above oral administration. Similarly,
      chronic administration (14 days) resulted in significantly higher levels of
      circulating BBR and DBG in DHB TD treated animals. Chronically treated rats were
      given a single dose of simvastatin with no observed change in the drugs
      bioavailability compared with control, suggesting the increased presence of BBR
      had no effect on simvastatin metabolism. This observation was further supported
      by consistent CYP3A4 expression across all treatment groups. Moreover, no changes
      in kidney and liver biomarkers, including alanine aminotransferase and alkaline
      phosphatase, were observed between treatment formats, and confirming previous
      reports that BBR has no effect on HMG-CoA expression. This study supports the
      safe use of transdermal compositions that improve on the poor bioavailability of
      oral berberine and have the potential to be more efficacious in the treatment of
      dyslipidemia or hypercholesterolemia.

PMID- 29579097
TI  - S-allylmercapto-N-acetylcysteine protects against oxidative stress and extends
      lifespan in Caenorhabditis elegans.
AB  - S-allylmercapto-N-acetylcysteine (ASSNAC) was shown in our previous study to
      activate Nrf2-mediated processes and increase glutathione level and resistance to
      oxidative stress in cultured endothelial cells. In this study, we explored the
      antioxidant protective effect of ASSNAC in Caenorhabditis elegans (C. elegans).
      Treatment of gst-4 reporter strain (CL2166) with increasing concentrations of
      ASSNAC (0.2 to 20 mM) for 24 hours and with ASSNAC (10 mM) for various time
      periods demonstrated a significant concentration- and time-dependent increase in
      Glutathione S-transferase (GST) gene expression (up to 60-fold at 20 mM after 24
      hours). In addition, ASSNAC (2 mM; 24 hours) treatment of C. elegans strains N2
      (wild type strain), gst-4 reporter (CL2166) and temperature sensitive sterile
      strain (CF512) significantly increased GST enzyme activity by 1.9-, 1.5- and 1.8
      fold, respectively. ASSNAC (2.0 mM; 24 hours) increased the reduced glutathione
      content in N2 and CF512 strains by 5.9- and 4.9-fold, respectively. Exposure of
      C. elegans (N2 strain) to a lethal concentration of H2O2 (3.5 mM; 120 min)
      resulted in death of 88% of the nematodes while pretreatment with ASSNAC (24
      hours) reduced nematodes death in a concentration-dependent manner down to 8% at
      2.0 mM. C. elegans nematodes (strain CF512) cultured on agar plates containing
      ASSNAC (0.5 to 5.0 mM) demonstrated a significant increase in lifespan compared
      to control (mean lifespan 26.45 +/- 0.64 versus 22.90 +/- 0.59 days; log-rank p
      <= 0.001 at 2.0 mM) with a maximal lifespan of 40 versus 36 days. In conclusion,
      ASSNAC up-regulates the GST gene expression and enzyme activity as well as the
      glutathione content in C. elegans nematodes and thereby increases their
      resistance to oxidative stress and extends their lifespan.

PMID- 29579098
TI  - Low intensity vibration of ankle muscles improves balance in elderly persons at
      high risk of falling.
AB  - In our study we examined postural performance of young healthy persons (HY),
      elderly healthy persons (HE), and elderly persons at high risk of falling (FR).
      Anterio-posterior (AP) and medio-lateral (ML) ankle and hip angular deviations,
      as well as linear displacements of the center of mass (COM) were assessed in
      persons standing with eyes either open or closed, while none, and 40 and 30 Hz
      vibrations were applied bilaterally to the ankle muscle gastrocnemius. During
      quiet standing with eyes open, balance parameters in FR group differed from those
      in healthy groups. ML ankle and hip angular deviations, as well as COM linear
      displacements were noticeably larger in FR group. During quiet standing with eyes
      closed, all balance parameters in participants of all groups had a clear trend to
      increase. During standing with eyes open, 40 Hz vibration increased all but one
      balance parameter within HY group, ankle angular deviations in HE group, but none
      in FR group. In response to 30 Hz vibration, only ankle angular deviations and
      COM linear displacements increased in HY group. There were no changes in both
      elderly groups. During standing with eyes closed, 40 and 30 Hz vibrations did not
      produce consistent changes in balance parameters in HY and HE groups. In FR
      persons, 40 Hz vibration did not change balance parameters. However, in FR
      groups, 30 Hz vibration decreased ankle and hip angular deviations, and COM
      linear displacements. The major result of the study is a finding that low
      intensity vibration of ankle muscles makes balance better in elderly persons at
      high risk of falling. This result is clinically relevant because it suggests that
      applying mild vibration to ankle muscles while standing and walking might benefit
      elderly persons, improving their postural performance and reducing a risk of
      unexpected falls.

PMID- 29579099
TI  - Severe influenza A(H1N1)pdm09 in pregnant women and neonatal outcomes, State of
      Sao Paulo, Brazil, 2009.
AB  - To investigate the factors associated with death and describe the gestational
      outcomes in pregnant women with influenza A(H1N1)pdm09, we conducted a case
      control study (deaths and recovered) in hospitalized pregnant women with
      laboratory-confirmed influenza A(H1N1)pdm09 with severe acute respiratory illness
      (SARI) in the state of Sao Paulo from June 9 to December 1, 2009. All cases were
      evaluated, and four controls that were matched by the epidemiological week of
      hospitalization of the case were randomly selected for each case. Cases and
      controls were selected from the National Disease Notification System-SINAN
      Influenza-web. The hospital records from 126 hospitals were evaluated, and home
      interviews were conducted using standardized forms. A total of 48 cases and 185
      controls were investigated. Having had a previous health visit to a healthcare
      provider for an influenza episode before hospital admission was a risk factor for
      death (adjusted OR (ORadj) of 7.93, 95% CI 2.19-28.69). Although not significant
      in the multiple analysis (ORadj of 2.13, 95% CI 0.91-5.00), the 3rd trimester
      deserves attention, with an OR = 2.22, 95% CI 1.13-4.37 in the univariate
      analysis. Antiviral treatment was a protective factor when administered within 48
      hours of symptom onset (ORadj = 0.16, 95% CI 0.05-0.50) and from 48 to 72 hours
      (ORadj = 0.09, 95% CI 0.01-0.87). There was a higher proportion of fetal deaths
      and preterm births among cases (p = 0.001) and live births with low weight (p =
      0.019), compared to control subjects who gave birth during hospitalization. After
      discharge, control subjects had a favorable neonatal outcome. Early antiviral
      treatment during the presence of a flu-like illness is an important factor in
      reducing mortality from influenza in pregnant women and unfavorable neonatal
      outcomes. It is important to monitor pregnant women, particularly in the 3rd
      trimester of gestation, with influenza illness for diagnosis and early treatment.

PMID- 29579100
TI  - Cerium enhances germination and shoot growth, and alters mineral nutrient
      concentration in rice.
AB  - Cerium (Ce) belongs to the rare earth elements (REEs), and although it is not
      essential for plants, it can stimulate growth and other physiological processes.
      The objective of this research was to evaluate the effect of Ce on seed
      germination, initial seedling growth, and vegetative growth in rice (Oryza sativa
      L.) cv. Morelos A-98. During the germination process, the seeds were treated with
      Ce concentrations of 0, 4, 8, and 12 MUM; after 5 d, germination percentage was
      recorded and after 10 d seedling growth was measured. For vegetative growth, a
      hydroponic system was established where 14-d-old plants without previous Ce
      treatment were transferred into nutrient solution. After two weeks of
      acclimatizing, 0, 25, 50, and 100 MUM Ce were added to the nutrient solution for
      28 d. Ce significantly increased germination and the initial growth variables of
      the seedlings. During vegetative growth, Ce increased plant height, number of
      tillers, root volume, and shoot fresh and dry biomass, without affecting root
      biomass weight. With low Ce concentrations (25 and 50 MUM), the concentrations of
      chlorophylls and amino acids in the shoots were similar to those in the control,
      like amino acid concentration in the roots at a concentration of 25 MUM Ce.
      Conversely, the concentration of total sugars increased in the shoot with the
      application of 25, 50, and 100 MUM Ce, and in the roots with the application of
      50 MUM Ce. Also, Ce did not affect the concentration of macro or micronutrients
      in the shoots. However, in the roots, the high Ce concentration decreased the
      concentrations of Ca, Fe, Mn, and Zn, while the Mg concentration increased. Our
      results indicate that Ce, at the right concentrations, can function as a
      biostimulant in rice germination and growth.

PMID- 29579101
TI  - Characterization of noise in multistable genetic circuits reveals ways to
      modulate heterogeneity.
AB  - Random fluctuations in the amount of cellular components like mRNA and protein
      molecules are inevitable due to the stochastic and discrete nature of biochemical
      reactions. If large enough, this so-called "cellular noise" can lead to random
      transitions between the expression states of a multistable genetic circuit. That
      way, heterogeneity within isogenic populations is created. Our aim is to
      understand which dynamical features of a simple autoregulatory system determine
      its intrinsic noise level, and how they can be modified in order to regulate
      state-transitions. To that end, novel mathematical methods for the state
      dependent characterization and prediction of noise in multistable systems are
      developed. First, we introduce the hybrid LNA, a modified version of the Linear
      Noise Approximation. It yields good predictions on variances of mRNA and protein
      fluctuations, even for reaction systems comprising low-copy-number components
      (e.g. mRNA) and highly nonlinear reaction rates. Furthermore, the temporal
      structure of fluctuations and the skewness of the protein distribution are
      characterized via state-dependent protein burst sizes and burst frequencies.
      Based on this mathematical framework, we develop graphical methods which support
      the intuitive design of regulatory circuits with a desired noise pattern. The
      methods are then used to predict how overall noise in the system can be adapted,
      and how state-specific noise modifications are possible that allow, e.g., the
      generation of unidirectional transitions. Our considerations are validated by
      stochastic simulations. This way, a design of genetic circuits is possible that
      takes population heterogeneity into account and is valuable in applications of
      synthetic biology and biotechnology. Moreover, natural phenomena like the bimodal
      development of genetic competence can be studied.

PMID- 29579102
TI  - Association between cognitive function and supplementation with omega-3 PUFAs and
      other nutrients in >= 75 years old patients: A randomized multicenter study.
AB  - A few studies have assessed the association between omega-3 polyunsaturated fatty
      acids (n-3 PUFA) and cognitive impairment (CI) in very old adults. The aim of
      this study was to evaluate the effect of a multinutrient supplementation rich in
      n-3 PUFA on the cognitive function in an institutionalized >=75-year-old
      population without CI or with mild cognitive impairment (MCI). A multicenter
      placebo-controlled double-blind randomized trial was conducted between 2012 and
      2013. Cognitive function was assessed at baseline and after one year using 4
      neuropsychological tests. Nutritional status was assessed using Mini Nutritional
      Assessment (MNA). Interaction between Mini-Mental State Examination (MMSE) score
      and nutritional status were analyzed using linear regression models. A total of
      99 participants were randomized to receive placebo or pills rich in n-3 PUFA.
      After 1-year follow-up, both groups decreased their MMSE score (-1.18, SD:0. 53
      and -0.82, SD:0. 63, p = 0.67 for the control and the intervention group
      respectively). The memory subscale of the MMSE showed an improvement (+0.26,
      SD:0.18) in the intervention group against a worsening in the control group (
      0.11, SD: 0.14; p = 0.09 for differences between groups). Patients at
      intervention group with normal nutritional status (MNA >=24) showed an
      improvement in the MMSE (+1.03, p = 0.025 for differences between 1-y and
      baseline measurements) against a worsening in the group with malnutrition
      (MNA<24) (-0.4, p = 0.886 for differences between 1-y and baseline; p of
      interaction p = 0.05). Supplementation with n-3 PUFA did not show an improvement
      in the global cognitive function in institutionalized elderly people without CI
      or with MCI. They only suggest an apparent improvement in memory loss if
      previously they were well nourished.

PMID- 29579103
TI  - A metagenomic viral discovery approach identifies potential zoonotic and novel
      mammalian viruses in Neoromicia bats within South Africa.
AB  - Species within the Neoromicia bat genus are abundant and widely distributed in
      Africa. It is common for these insectivorous bats to roost in anthropogenic
      structures in urban regions. Additionally, Neoromicia capensis have previously
      been identified as potential hosts for Middle East respiratory syndrome (MERS)
      related coronaviruses. This study aimed to ascertain the gastrointestinal virome
      of these bats, as viruses excreted in fecal material or which may be replicating
      in rectal or intestinal tissues have the greatest opportunities of coming into
      contact with other hosts. Samples were collected in five regions of South Africa
      over eight years. Initial virome composition was determined by viral metagenomic
      sequencing by pooling samples and enriching for viral particles. Libraries were
      sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37
      million reads. Bioinformatics analysis of the high throughput sequencing data
      detected the full genome of a novel species of the Circoviridae family, and also
      identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae,
      Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families.
      Metagenomic sequencing data was insufficient to determine the viral diversity of
      certain families due to the fragmented coverage of genomes and lack of suitable
      sequencing depth, as some viruses were detected from the analysis of reads-data
      only. Follow up conventional PCR assays targeting conserved gene regions for the
      Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm
      metagenomic data and generate additional sequences to determine genetic
      diversity. The complete coding genome of a MERS-related coronavirus was recovered
      with additional amplicon sequencing on the MiSeq platform. The new genome shared
      97.2% overall nucleotide identity to a previous Neoromicia-associated MERS
      related virus, also from South Africa. Conventional PCR analysis detected diverse
      adenovirus and herpesvirus sequences that were widespread throughout Neoromicia
      populations in South Africa. Furthermore, similar adenovirus sequences were
      detected within these populations throughout several years. With the exception of
      the coronaviruses, the study represents the first report of sequence data from
      several viral families within a Southern African insectivorous bat genus;
      highlighting the need for continued investigations in this regard.

PMID- 29579104
TI  - A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of
      Cdc42 and membrane protrusions.
AB  - De novo formation of epithelial cell-cell contacts relies on actin-based
      protrusions as well as tightly controlled turnover of junctional actin once cells
      encounter each other and adhesion complexes assemble. The specific contributions
      of individual actin regulators on either protrusion formation or junctional actin
      turnover remain largely unexplored. Based on our previous findings of Formin-like
      2 (FMNL2)-mediated control of junctional actin dynamics, we investigated its
      potential role in membrane protrusions and impact on newly forming epithelial
      contacts. CRISPR/Cas9-mediated loss of FMNL2 in human MCF10A cells combined with
      optogenetic control of Rac1 activity confirmed its critical function in the
      establishment of intercellular contacts. While lamellipodial protrusion rates
      remained unaffected, FMNL2 knockout cells were characterized by impaired
      filopodia formation similar to depletion of the Rho GTPase Cdc42. Silencing of
      Cdc42, however, failed to affect FMNL2-mediated contact formation. Hence, we
      propose a cell-cell contact-specific and Rac1-mediated function of FMNL2 entirely
      independent of Cdc42. Consistent with this, direct visualizations of native
      epithelial junction formation revealed a striking and specifically Rac1- and not
      Cdc42-dependent recruitment of FMNL2 to newly forming junctions as well as
      established cell-cell contacts within epithelial sheets.

PMID- 29579105
TI  - Neisseria Heparin Binding Antigen is targeted by the human alternative pathway C3
      convertase.
AB  - Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein
      specific for Neisseria and constitutes one of the three main protein antigens of
      the Bexsero vaccine. Meningococcal and human proteases, cleave NHBA protein
      upstream or downstream of a conserved Arg-rich region, respectively. The cleavage
      results in the release of the C-terminal portion of the protein. The C-terminal
      fragment originating from the processing of meningococcal proteases, referred to
      as C2 fragment, exerts a toxic effect on endothelial cells altering the
      endothelial permeability. In this work, we reported that recombinant C2 fragment
      has no influence on the integrity of human airway epithelial cell monolayers,
      consistent with previous findings showing that Neisseria meningitidis traverses
      the epithelial barrier without disrupting the junctional structures. We showed
      that epithelial cells constantly secrete proteases responsible for a rapid
      processing of C2 fragment, generating a new fragment that does not contain the
      Arg-rich region, a putative docking domain reported to be essential for C2
      mediated toxic effect. Moreover, we found that the C3-convertase of the
      alternative complement pathway is one of the proteases responsible for this
      processing. Overall, our data provide new insights on the cleavage of NHBA
      protein during meningococcal infection. NHBA cleavage may occur at different
      stages of the infection, and it likely has a different role depending on the
      environment the bacterium is interacting with.

PMID- 29579107
TI  - Correction: Prime incision: A minimally invasive approach to breast cancer
      surgical treatment-A 2 cohort retrospective comparison with conventional breast
      conserving surgery.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191056.].

PMID- 29579106
TI  - Impact of nutritional stress on drug susceptibility and biofilm structures of
      Burkholderia pseudomallei and Burkholderia thailandensis grown in static and
      microfluidic systems.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis and regarded as a
      bioterrorism threat. It can adapt to the nutrient-limited environment as the
      bacteria can survive in triple distilled water for 16 years. Moreover, B.
      pseudomallei exhibits intrinsic resistance to diverse groups of antibiotics in
      particular while growing in biofilms. Recently, nutrient-limited condition
      influenced both biofilm formation and ceftazidime (CAZ) tolerance of B.
      pseudomallei were found. However, there is no information about how nutrient
      limitation together with antibiotics used in melioidosis treatment affects the
      structure of the biofilm produced by B. pseudomallei. Moreover, no comparative
      study to investigate the biofilm architectures of B. pseudomallei and the related
      B. thailandensis under different nutrient concentrations has been reported.
      Therefore, this study aims to provide new information on the effects of four
      antibiotics used in melioidosis treatment, viz. ceftazidime (CAZ), imipenem
      (IMI), meropenem (MEM) and doxycycline (DOX) on biofilm architecture of B.
      pseudomallei and B. thailandensis with different nutrient concentrations under
      static and flow conditions using confocal laser scanning microscopy. Impact of
      nutritional stress on drug susceptibility of B. pseudomallei and B. thailandensis
      grown planktonically or as biofilm was also evaluated. The findings of this study
      indicate that nutrient-limited environment enhanced survival of B. pseudomallei
      in biofilm after exposure to the tested antibiotics. The shedding planktonic B.
      pseudomallei and B. thailandensis were also found to have increased CAZ tolerance
      in nutrient-limited environment. However, killing activities of MEM and IMI were
      stronger than CAZ and DOX on B. pseudomallei and B. thailandensis both in
      planktonic cells and in 2-day old biofilm. In addition, MEM and IMI were able to
      inhibit B. pseudomallei and B. thailandensis biofilm formation to a larger extend
      compared to CAZ and DOX. Differences in biofilm architecture were observed for
      biofilms grown under static and flow conditions. Under static conditions,
      biofilms grown in full strength modified Vogel and Bonner's medium (MVBM) showed
      honeycomb-like architecture while a knitted-like structure was observed under
      limited nutrient condition (0.1*MVBM). Under flow conditions, biofilms grown in
      MVBM showed a multilayer structure while merely dispersed bacteria were found
      when grown in 0.1*MVBM. Altogether, this study provides more insight on the
      effect of four antibiotics against B. pseudomallei and B. thailandensis in
      biofilm under different nutrient and flow conditions. Since biofilm formation is
      believed to be involved in disease relapse, MEM and IMI may be better therapeutic
      options than CAZ for melioidosis treatment.

PMID- 29579108
TI  - The association between BMI and body weight perception among children and
      adolescents in Jilin City, China.
AB  - OBJECTIVES: We evaluated the association between BMI and body weight perception
      in a sample of children and adolescents. METHODS: A cross-sectional school-based
      study was conducted among 7-18 year-olds (N = 9727) from 4 districts in Jilin
      City, China. We calculated BMI from measured weight and height and assessed body
      weight perception using a single questionnaire item. We analyzed these data using
      SPSS version 20.0. RESULTS: Approximately 19.8% of these youth perceived
      themselves as underweight, 57.8% as normal weight, and 22.4% as overweight. In
      reality, 4.9% were underweight, 64.3% were normal weight, and 30.8% were
      overweight. Furthermore, approximately 66.4% of these Chinese youth correctly
      perceived their body image, 28.2% underestimated their true body image, and 5.4%
      overestimated their weight status. Girls were more likely than boys to
      overestimate their weight (chi2 = 135.4, p < 0.05). Adolescents 13-18 years old
      were more likely than children 7-12 years old to overestimate their weight (chi2
      = 248.4, p < 0.05). Senior high school students were the most likely to
      overestimate their weight (chi2 = 297.6, p < 0.05). Kappa tests revealed
      significant differences in consistency analysis of BMI and body weight perception
      (Kappa = 0.352, p < 0.05). Kappa < 0.4, the consistency of BMI and body weight
      perception was poor. CONCLUSIONS: A mismatch existed between BMI and body weight
      perception among these children and adolescents. Thus, schools and parents should
      take steps to help them improve weight management and overall health awareness.

PMID- 29579109
TI  - Using data linkage to electronic patient records to assess the validity of
      selected mental health diagnoses in English Hospital Episode Statistics (HES).
AB  - BACKGROUND: Administrative data can be used to support research, such as in the
      UK Biobank. Hospital Episode Statistics (HES) are national data for England that
      include contain ICD-10 diagnoses for inpatient mental healthcare episodes, but
      the validity of these diagnoses for research purposes has not been assessed.
      METHODS: 250 peoples' HES records were selected based on a HES recorded inpatient
      stay at the South London and Maudsley NHS Foundation Trust with a diagnosis of
      schizophrenia, a wider schizophrenia spectrum disorder, bipolar affective
      disorder or unipolar depression. A gold-standard research diagnosis was made
      using Clinical Records Interactive Search pseudonymised electronic patient
      records using, and the OPCRIT+ algorithm. RESULTS: Positive predictive value at
      the level of lifetime psychiatric disorder was 100%, and at the level of lifetime
      diagnosis in the four categories of schizophrenia, wider schizophrenia spectrum,
      bipolar or unipolar depression was 73% (68-79). Agreement varied by diagnosis,
      with schizophrenia having the highest PPV at 90% (80-96). Each person had an
      average of five psychiatric HES records. An algorithm that looked at the last
      recorded psychiatric diagnosis led to greatest overall agreement with the
      research diagnosis. DISCUSSION: For people who have a HES record from a
      psychiatric admission with a diagnosis of schizophrenia spectrum disorder,
      bipolar affective disorder or unipolar depression, HES records appear to be a
      good indicator of a mental disorder, and can provide a diagnostic category with
      reasonable certainty. For these diagnoses, HES records can be an effective way of
      ascertaining psychiatric diagnosis.

PMID- 29579110
TI  - Correction: Genetic structure provides insights into the geographic origins and
      temporal change in the invasive charru mussel (Sururu) in the southeastern United
      States.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180619.].

PMID- 29579111
TI  - Micro-habitat distribution drives patch quality for sub-tropical rocky plateau
      amphibians in the northern Western Ghats, India.
AB  - The importance of patch quality for amphibians is frequently overlooked in
      distribution models. Here we demonstrate that it is highly important for the
      persistence of endemic and endangered amphibians found in the threatened and
      fragile ecosystems that are the rocky plateaus in Western Maharashtra, India.
      These plateaus are ferricretes of laterite and characterise the northern section
      of the Western Ghats/Sri Lanka Biodiversity Hotspot, the eighth most important
      global hotspot and one of the three most threatened by population growth. We
      present statistically supported habitat associations for endangered and data
      deficient Indian amphibians, demonstrating significant relationships between
      individual species and their microhabitats. Data were collected during early
      monsoon across two seasons. Twenty-one amphibian taxa were identified from 14
      lateritic plateaus between 67 and 1179m above sea level. Twelve of the study taxa
      had significant associations with microhabitats using a stepwise analysis of the
      AICc subroutine (distLM, Primer-e, v7). Generalist taxa were associated with
      increased numbers of microhabitat types. Non-significant associations are
      reported for the remaining 9 taxa. Microhabitat distribution was spatially
      structured and driven by climate and human activity. Woody plants were associated
      with 44% of high-elevation taxa. Of the 8 low-elevation taxa 63% related to water
      bodies and 60% of those were associated with pools. Rock size and abundance were
      important for 33% of high elevation specialists. Three of the 4 caecilians were
      associated with rocks in addition to soil and stream presence. We conclude the
      plateaus are individualistic patches whose habitat quality is defined by their
      microhabitats within climatic zones.

PMID- 29579112
TI  - Maternal invasion history of Aedes aegypti and Aedes albopictus into the Isthmus
      of Panama: Implications for the control of emergent viral disease agents.
AB  - Despite an increase in dengue outbreaks and the arrival of chikungunya and Zika
      disease in Panama, studies on the demographic history of the invasive Aedes
      mosquitoes that are the principle vectors of these diseases are still lacking in
      this region. Here, we assess the genetic diversity of these mosquitoes in order
      to decipher their invasion histories into the Isthmus of Panama. DNA sequences
      from the mitochondrial cytochrome C oxidase I gene obtained from 30 localities in
      10 provinces confirmed the presence of more than one mitochondrial haplogroup
      (i.e., maternal lineage) in each species. The invasion of Aedes albopictus was
      likely from temperate European countries, as the most frequent and widespread
      haplogroup in Panama harbored variants that are uncommon elsewhere in the
      Americas. Two infrequent and geographically restricted Ae. albopictus haplotypes
      appear to have subsequently invaded Panama from neighboring Costa Rica and the
      USA, respectively. In addition, we recovered two deeply divergent mitochondrial
      clades in Panamanian Aedes aegypti. The geographic origins of these clades is
      unknown, given that divergence in the mitochondrial genome is probably due to
      ancient population processes within the native range of Ae. aegypti, rather than
      due to its global expansion out of Africa. However, Panamanian Ae. aegypti
      mitochondrial sequences within the first clade were closely related to others
      from Colombia, Bolivia, Brazil, Mexico and the USA, suggesting two separate
      invasions from Western Hemisphere source populations. The pattern of increased
      genetic diversity in Aedes mosquitoes in Panama is likely facilitated by the
      numerous land and water inter-connections across the country, which allows them
      to enter via sea- and land-transportation from Europe, North, Central and South
      America. Our results here should be considered in disease mitigation programs if
      emergent arboviruses are to be effectively diminished in Panama through vector
      suppression.

PMID- 29579113
TI  - Streptococcal M protein promotes IL-10 production by cGAS-independent activation
      of the STING signaling pathway.
AB  - From an evolutionary point of view a pathogen might benefit from regulating the
      inflammatory response, both in order to facilitate establishment of colonization
      and to avoid life-threatening host manifestations, such as septic shock. In
      agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling
      to limit detrimental inflammation in infected mice, but the host-pathogen
      interactions and mechanisms responsible for induction of the type I IFN response
      have remained unknown. Here we used a macrophage infection model and report that
      S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a
      function that was mapped to the B- and C-repeat regions of the M5 protein.
      Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and
      production of type I IFN occurred via M protein-dependent activation of the STING
      signaling pathway. Activation of STING was independent of the cytosolic double
      stranded DNA sensor cGAS, and infection did not induce detectable release into
      the cytosol of either mitochondrial, nuclear or bacterial DNA-indicating DNA
      independent activation of the STING pathway in S. pyogenes infected macrophages.
      These findings provide mechanistic insight concerning how S. pyogenes induces the
      type I IFN response and identify a previously unrecognized macrophage-modulating
      role for the streptococcal M protein that may contribute to curb the inflammatory
      response to infection.

PMID- 29579114
TI  - Chlorophyll, carotenoid and vitamin C metabolism regulation in Actinidia
      chinensis 'Hongyang' outer pericarp during fruit development.
AB  - Ascorbic acid (AsA), chlorophyll and carotenoid contents and their associated
      gene expression patterns were analysed in Actinidia chinensis 'Hongyang' outer
      pericarp. The results showed chlorophyll degradation during fruit development and
      softening, exposed the yellow carotenoid pigments. LHCB1 and CLS1 gene
      expressions were decreased, while PPH2 and PPH3 gene expressions were increased,
      indicating that downregulation of chlorophyll biosynthesis and upregulation of
      its degradation, caused chlorophyll degradation. A decrease in the expression of
      the late carotenoid biosynthesis and maintenance genes (LCYB1, LCYE1, CYP1, CYP2,
      ZEP1, VDE1, VDE2, and NCED2) and degradation gene (CCD1), showed biosynthesis and
      degradation of carotenoid could be regulatory factors involved in fruit
      development. Most genes expression data of L-galactose and recycling pathway were
      agreement with the AsA concentrations in the fruit, suggesting these are the
      predominant pathways of AsA biosynthesis. GMP1, GME1 and GGP1 were identified as
      the key genes controlling AsA biosynthesis in 'Hongyang' outer pericarp.

PMID- 29579115
TI  - Metabolic Syndrome and cognitive decline in the elderly: A systematic review.
AB  - BACKGROUND: Metabolic Syndrome (MetS) refers to a cluster of metabolic
      disturbances which is associated with increased risk for vascular and
      degenerative conditions in general population. Although the relationship between
      vascular risk factors and dementia is undisputable, additional hazard for
      cognitive decline in older population with concurrent metabolic disorders still
      waits to be demonstrated. The present review aims to analyze data on MetS and
      risk for cognitive decline in elderly persons. METHODS: Database searches were
      performed in Medline, ISI and PsycINFO for articles assessing cognitive
      performances of older subjects with MetS. RESULTS: Of a total of 505 studies, 25
      were selected for the review. Risk of selection biases was identified in all the
      studies. Although all articles followed recognized diagnostic recommendations for
      MetS, minor criteria modifications were detected in most of them. Hyperglycemia
      was consistently associated with impaired cognitive performances in older
      individuals, but the role of MetS for cognitive decline and for the onset of
      dementia showed heterogeneous results. DISCUSSION: Current available data in the
      literature concerning the impact of MetS on the cognition of older population is
      inconclusive and based on inconsistent evidence. Differential effects of
      individual MetS components and factors associated with the age of the sample may
      have accounted for divergent findings among articles, but larger and higher
      quality studies in this field are still needed.

PMID- 29579116
TI  - Reference gene selection for qRT-PCR analysis of flower development in
      Lagerstroemia indica and L. speciosa.
AB  - Quantitative real-time polymerase chain reaction (qRT-PCR) is a prevalent method
      for gene expression analysis, depending on the stability of the reference genes
      for data normalization. Lagerstroemia indica and L. speciosa are popular
      ornamental plants which are famous for the long flowering period. However, no
      systematic studies on reference genes in Lagerstroemia have yet been conducted.
      In the present study, we selected nine candidate reference genes (GAPDH, TUA,
      TUB, 18S, RPII, EF-1alpha, ATC, EIF5A and CYP) and evaluated their expression
      stability in different tissues during floral development of L. indica and L.
      speciosa using four algorithms (geNorm, NormFinder, BestKeeper and, RefFinder).
      Results showed that RPII and EF-1alpha were the most stably expressed and
      suitable reference genes for both of Lagerstroemia species. Moreover, ACT
      exhibited high expression stability in L. indica and GAPDH was a suitable
      reference gene for L. speciosa in different flower development stages. TUB was an
      unsuitable reference gene for gene expression normalization due to significant
      variations in expression across all samples. Finally, we verified the reliability
      of the selected candidate reference genes by amplifying an AGAMOUS homolog
      (LsAG1) of Arabidopsis thaliana. This study provides a list of suitable reference
      genes, thereby broadening the genetic basis of the gene expression patterns in
      Lagerstroemia species.

PMID- 29579117
TI  - Correction: The anti-tumorigenic activity of A2M-A lesson from the naked mole
      rat.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189514.].

PMID- 29579118
TI  - Niche overlap between a cold-water coral and an associated sponge for
      isotopically-enriched particulate food sources.
AB  - The cold-water coral Lophelia pertusa is an ecosystem engineer that builds reef
      structures on the seafloor. The interaction of the reef topography with
      hydrodynamics is known to enhance the supply of suspended food sources to the
      reef communities. However, the reef framework is also a substrate for other
      organisms that may compete for the very same suspended food sources. Here, we
      used the passive suspension feeder Lophelia pertusa and the active suspension
      feeding sponge Hymedesmia coriacea as model organisms to study niche overlap
      using isotopically-enriched algae and bacteria as suspended food sources. The
      coral and the sponge were fed with a combination of 13C-enriched bacteria/15N
      enriched algae or 15N-enriched bacteria/13C-enriched algae, which was
      subsequently traced into bulk tissue, coral skeleton and dissolved inorganic
      carbon (i.e. respiration). Both the coral and the sponge assimilated and respired
      the suspended bacteria and algae, indicating niche overlap between these species.
      The assimilation rates of C and N into bulk tissue of specimens incubated
      separately were not significantly different from assimilation rates during
      incubations with co-occurring corals and sponges. Hence, no evidence for
      exploitative resource competition was found, but this is likely due to the
      saturating experimental food concentration that was used. We do not rule out that
      exploitative competition occurs in nature during periods of low food
      concentrations. Food assimilation and respiration rates of the sponge were almost
      an order of magnitude higher than those of the cold-water coral. We hypothesize
      that the active suspension feeding mode of the sponge explains the observed
      differences in resource uptake as opposed to the passive suspension feeding mode
      of the cold-water coral. These feeding mode differences may set constraints on
      suitable habitats for cold-water corals and sponges in their natural habitats.

PMID- 29579119
TI  - High levels of caregiver burden in Prader-Willi syndrome.
AB  - OBJECTIVES: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental
      disorder that is characterized by hyperphagia, developmental delay, incomplete
      sexual development, mild-to-moderate intellectual disability, and a variety of
      challenging behavioral and psychiatric symptoms. The characteristics of PWS can
      be difficult for caregivers to cope with and are likely to cause significant and
      long- term caregiver burden. The current study examined burden in 142 caregivers
      of children and adults with PWS living in the US using the Zarit Burden Interview
      (ZBI). The study aimed to measure the level of burden in caregivers of
      individuals with PWS, to explore the impact of PWS on caregiver quality of life,
      and to assess ZBI as an indicator of that impact. RESULTS: Caregivers
      participating in this study were predominantly mothers, 30-59 years old, non
      Hispanic Whites, married or in a relationship, with an annual household income
      slightly distributed towards higher income. Nearly 90% of the caregiver's
      children with PWS lived at home. Caregivers experienced high caregiver burden
      with an average ZBI score of 44.4 +/- 15.4. ZBI scores were highest for
      caregivers of teenage and young adult individuals with PWS (49.2 +/- 14.6 and
      49.2 +/- 14.1, respectively), while those caring for older adults (>30) and the
      youngest age group had lower scores (38.6 +/-10.5 and 34.8 +/-12.5,
      respectively). Caregivers reported that caring for a person with PWS negatively
      impacted their romantic relationship, ability to work, sleep, and mood. Whereas
      we did not find strong correlations between family income or level of help the
      caregiver receives and ZBI scores, the results showed significant correlations
      and a linear relationship between ZBI scores and caregiver depressed mood,
      feelings of anxiety, negative romantic relationship impact, as well as sleep and
      work disruption. CONCLUSIONS: Our study reveals that PWS incurs high caregiver
      burden and impacts many aspects of the lives of caregiver. We identified the ZBI
      as a good predictor of that impact. Our findings draw attention to the critical
      unmet need for support for caregivers of individuals with PWS.

PMID- 29579120
TI  - HSV-1-induced disruption of transcription termination resembles a cellular stress
      response but selectively increases chromatin accessibility downstream of genes.
AB  - Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of
      transcription termination (DoTT) of most cellular genes, resulting in extensive
      intergenic transcription. Similarly, cellular stress responses lead to gene
      specific transcription downstream of genes (DoG). In this study, we performed a
      detailed comparison of DoTT/DoG transcription between HSV-1 infection, salt and
      heat stress in primary human fibroblasts using 4sU-seq and ATAC-seq. Although
      DoTT at late times of HSV-1 infection was substantially more prominent than DoG
      transcription in salt and heat stress, poly(A) read-through due to DoTT/DoG
      transcription and affected genes were significantly correlated between all three
      conditions, in particular at earlier times of infection. We speculate that HSV-1
      either directly usurps a cellular stress response or disrupts the transcription
      termination machinery in other ways but with similar consequences. In contrast to
      previous reports, we found that inhibition of Ca2+ signaling by BAPTA-AM did not
      specifically inhibit DoG transcription but globally impaired transcription. Most
      importantly, HSV-1-induced DoTT, but not stress-induced DoG transcription, was
      accompanied by a strong increase in open chromatin downstream of the affected
      poly(A) sites. In its extent and kinetics, downstream open chromatin essentially
      matched the poly(A) read-through transcription. We show that this does not cause
      but rather requires DoTT as well as high levels of transcription into the genomic
      regions downstream of genes. This raises intriguing new questions regarding the
      role of histone repositioning in the wake of RNA Polymerase II passage downstream
      of impaired poly(A) site recognition.

PMID- 29579122
TI  - The Monty Hall problem revisited: Autonomic arousal in an inverted version of the
      game.
AB  - The asymmetry of autonomic arousal for potential losses and gains was assessed by
      the galvanic skin response (GSR) of participants playing classic and inverted
      versions of the Monty Hall problem (MHP). In both versions, the prize remained
      the same (a pen valued at L10 for the right answer), but in the modified version,
      prizes were received prior to choosing the door. Both experimental groups showed
      increased levels of GSR while completing the task, demonstrating increased
      autonomic arousal during the game. However, a robust difference in GSR was
      detected between classic and inverted versions of the MHP, thus demonstrating the
      differing autonomic arousal involved in deciding between the alternatives
      presented by the game. Participants experienced a stronger autonomic response
      when they could lose the prize than when they could win the prize. This
      experiment presents the first demonstration of this effect on the MHP. The
      stronger autonomic arousal for the inverted task may indicate a stronger
      emotional reaction and/or greater attentional focus than for the standard version
      of the task. These data demonstrate that potential losses increase arousal in
      more complex tasks than is typically shown.

PMID- 29579121
TI  - The combination of NAD+-dependent deacetylase gene deletion and the interruption
      of gluconeogenesis causes increased glucose metabolism in budding yeast.
AB  - Metabolic engineering focuses on rewriting the metabolism of cells to enhance
      native products or endow cells with the ability to produce new products. This
      engineering has the potential for wide-range application, including the
      production of fuels, chemicals, foods and pharmaceuticals. Glycolysis manages the
      levels of various secondary metabolites by controlling the supply of glycolytic
      metabolites. Metabolic reprogramming of glycolysis is expected to cause an
      increase in the secondary metabolites of interest. In this study, we constructed
      a budding yeast strain harboring the combination of triple sirtuin gene deletion
      (hst3? hst4? sir2?) and interruption of gluconeogenesis by the deletion of the
      FBP1 gene encoding fructose-1,6-bisphosphatase (fbp1?). hst3? hst4? sir2? fbp1?
      cells harbored active glycolysis with high glucose consumption and active ethanol
      productivity. Using capillary electrophoresis-time-of-flight mass spectrometry
      (CE-TOF/MS) analysis, hst3? hst4? sir2? fbp1? cells accumulated not only
      glycolytic metabolites but also secondary metabolites, including nucleotides that
      were synthesized throughout the pentose phosphate (PP) pathway, although various
      amino acids remained at low levels. Using the stable isotope labeling assay for
      metabolites, we confirmed that hst3? hst4? sir2? fbp1? cells directed the
      metabolic fluxes of glycolytic metabolites into the PP pathway. Thus, the
      deletion of three sirtuin genes (HST3, HST4 and SIR2) and the FBP1 gene can allow
      metabolic reprogramming to increase glycolytic metabolites and several secondary
      metabolites except for several amino acids.

PMID- 29579123
TI  - Temporal changes in electrocardiographic frontal QRS-T angle and survival in
      patients with heart failure.
AB  - BACKGROUND: Heart failure (HF) is associated with considerable mortality. The
      electrocardiographic frontal QRS-T angle is a simple parameter to measure,
      reflects changes in the direction of the repolarization sequence and predicts
      outcome in patients with HF. Data regarding temporal changes in the frontal QRS-T
      angle in patients with HF and its impact on outcome is limited. AIM: To evaluate
      temporal changes in the frontal QRS-T angle and its effect on survival in
      patients with HF. METHODS: Baseline and follow-up QRS-T angle were calculated
      from the frontal QRS and T axis of the 12-lead surface electrocardiogram.
      Patients were followed for survival. RESULTS: 2,929 HF patients were evaluated.
      Median interval between baseline ECG and follow-up ECG was 895 days, median
      follow-up time was 1526 days. Overall, the QRS-T angle tended to be stable, with
      minor changes in the angle over time. The median QRS-T angle change was +3
      degrees  (IQR -19 degrees  to +30 degrees ). Overall survival during follow-up
      was 60%. Cox regression analysis after adjustment for significant predictors
      demonstrated that the QRS-T angle was an incremental predictor of increased
      mortality. A widening of the QRS-T angle during follow-up was independently
      associated with an increase in mortality, evident with an increase of the QRS-T
      angle difference above 0 degrees  (P<0.0001 for the adjusted model). CONCLUSION:
      QRS-T angle is relatively stable in patients with HF and is a powerful predictor
      of outcome. Widening of the QRS-T angle has predictive value and is an ominous
      sign.

PMID- 29579124
TI  - Correction: Peripheral Organs of Dengue Fatal Cases Present Strong Pro
      Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES
      Producing Cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0168973.].

PMID- 29579125
TI  - Revocable identity-based proxy re-signature against signing key exposure.
AB  - Identity-based proxy re-signature (IDPRS) is a novel cryptographic primitive that
      allows a semi-trusted proxy to convert a signature under one identity into
      another signature under another identity on the same message by using a re
      signature key. Due to this transformation function, IDPRS is very useful in
      constructing privacy-preserving schemes for various information systems. Key
      revocation functionality is important in practical IDPRS for managing users
      dynamically; however, the existing IDPRS schemes do not provide revocation
      mechanisms that allow the removal of misbehaving or compromised users from the
      system. In this paper, we first introduce a notion called revocable identity
      based proxy re-signature (RIDPRS) to achieve the revocation functionality. We
      provide a formal definition of RIDPRS as well as its security model. Then, we
      present a concrete RIDPRS scheme that can resist signing key exposure and prove
      that the proposed scheme is existentially unforgeable against adaptive chosen
      identity and message attacks in the standard model. To further improve the
      performance of signature verification in RIDPRS, we introduce a notion called
      server-aided revocable identity-based proxy re-signature (SA-RIDPRS). Moreover,
      we extend the proposed RIDPRS scheme to the SA-RIDPRS scheme and prove that this
      extended scheme is secure against adaptive chosen message and collusion attacks.
      The analysis results show that our two schemes remain efficient in terms of
      computational complexity when implementing user revocation procedures. In
      particular, in the SA-RIDPRS scheme, the verifier needs to perform only a
      bilinear pairing and four exponentiation operations to verify the validity of the
      signature. Compared with other IDPRS schemes in the standard model, our SA-RIDPRS
      scheme greatly reduces the computation overhead of verification.

PMID- 29579126
TI  - Improved methods of DNA extraction from human spermatozoa that mitigate
      experimentally-induced oxidative DNA damage.
AB  - Current approaches for DNA extraction and fragmentation from mammalian
      spermatozoa provide several challenges for the investigation of the oxidative
      stress burden carried in the genome of male gametes. Indeed, the potential
      introduction of oxidative DNA damage induced by reactive oxygen species, reducing
      agents (dithiothreitol or beta-mercaptoethanol), and DNA shearing techniques used
      in the preparation of samples for chromatin immunoprecipitation and next
      generation sequencing serve to cofound the reliability and accuracy of the
      results obtained. Here we report optimised methodology that minimises, or
      completely eliminates, exposure to DNA damaging compounds during extraction and
      fragmentation procedures. Specifically, we show that Micrococcal nuclease (MNase)
      digestion prior to cellular lysis generates a greater DNA yield with minimal
      collateral oxidation while randomly fragmenting the entire paternal genome. This
      modified methodology represents a significant improvement over traditional
      fragmentation achieved via sonication in the preparation of genomic DNA from
      human spermatozoa for downstream applications, such as next-generation
      sequencing. We also present a redesigned bioinformatic pipeline framework
      adjusted to correctly analyse this form of data and detect statistically relevant
      targets of oxidation.

PMID- 29579127
TI  - Prognostic factors in epithelial ovarian cancer: A population-based study.
AB  - The overall survival (OS) of patients with ovarian cancer is poor while
      epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of
      the present study was to evaluate the clinico-pathologic characteristics,
      especially the prognostic factors, for patients with epithelial ovarian cancer
      (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to
      2012 was retrieved from the database of the Taiwan Cancer Registry. Data from
      2009 to 2013 for the respective cases from the claims database of Taiwan's
      National Health Insurance and National Death Registry were then retrieved.
      Potential prognostic factors were analyzed. The mean age at diagnosis of the
      2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were
      diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients
      with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and
      younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002,
      p<0.001, respectively) in multivariable analysis. For advanced-stage patients,
      histology (endometrioid type), taxane-based adjuvant chemotherapy, stage, and age
      at diagnosis had a significant impact on OS (p<0.001, p = 0.020, p<0.001,
      p<0.001, respectively). In conclusion, taxane-based chemotherapy impacts the
      outcome of patients with EOC. Personalized medicine may be needed for different
      histological types of EOC because of their different outcomes.

PMID- 29579128
TI  - Performance evaluation of Active Melioidosis Detect-Lateral Flow Assay (AMD-LFA)
      for diagnosis of melioidosis in endemic settings with limited resources.
AB  - Melioidosis is a fatal infection caused by the soil saprophyte Burkholderia
      pseudomallei. Early diagnosis and befitting medical management can significantly
      influence the clinical outcomes among patients with melioidosis. Witnessing an
      annual increment in the number of melioidosis cases, over the past few years,
      mainly from the developing tropical nations, the present study was undertaken to
      evaluate the diagnostic utility of Active Melioidosis DetectTMLateralFlow Assay
      (AMD-LFA), in comparison with enrichment culture and PCR. A total of 206clinical
      specimens obtained from 175 patients with clinical suspicion of melioidosis were
      considered for the evaluation. Positivity for B.pseudomallei using enrichment
      culture, PCR and AMD-LFA were observed among 63 (30.5%), 55 (26.6%) and 63
      (30.5%) specimens respectively. The AMD-LFA failed to detect melioidosis from 9
      culture-confirmed cases (6 whole blood specimens, 2 pus samples, and one synovial
      fluid). Further the test gave faint bands from 9 urine samples which were
      negative by culture and PCR. AMD-LFA demonstrated a sensitivity, specificity, of
      85.71%(CI:74.61% to 93.25%) and 93.62% (CI:88.23% to 97.04%), with positive
      predictive value of 85.71% (CI: 75.98% to 91.92%) and negative predictive value
      of 93.62% (CI:88.89% to 96.42%). The test needs further evaluation in view of the
      faint bands from negative urine samples, for incorporating the test as a point of
      care assay.In view of its rapidity and ease of testing AMD-LFA might be useful in
      early diagnosis of melioidosis at resource constraint settings.

PMID- 29579129
TI  - Estimating large carnivore populations at global scale based on spatial
      predictions of density and distribution - Application to the jaguar (Panthera
      onca).
AB  - Broad scale population estimates of declining species are desired for
      conservation efforts. However, for many secretive species including large
      carnivores, such estimates are often difficult. Based on published density
      estimates obtained through camera trapping, presence/absence data, and globally
      available predictive variables derived from satellite imagery, we modelled
      density and occurrence of a large carnivore, the jaguar, across the species'
      entire range. We then combined these models in a hierarchical framework to
      estimate the total population. Our models indicate that potential jaguar density
      is best predicted by measures of primary productivity, with the highest densities
      in the most productive tropical habitats and a clear declining gradient with
      distance from the equator. Jaguar distribution, in contrast, is determined by the
      combined effects of human impacts and environmental factors: probability of
      jaguar occurrence increased with forest cover, mean temperature, and annual
      precipitation and declined with increases in human foot print index and human
      density. Probability of occurrence was also significantly higher for protected
      areas than outside of them. We estimated the world's jaguar population at 173,000
      (95% CI: 138,000-208,000) individuals, mostly concentrated in the Amazon Basin;
      elsewhere, populations tend to be small and fragmented. The high number of
      jaguars results from the large total area still occupied (almost 9 million km2)
      and low human densities (< 1 person/km2) coinciding with high primary
      productivity in the core area of jaguar range. Our results show the importance of
      protected areas for jaguar persistence. We conclude that combining modelling of
      density and distribution can reveal ecological patterns and processes at global
      scales, can provide robust estimates for use in species assessments, and can
      guide broad-scale conservation actions.

PMID- 29579130
TI  - Epidemiology and outcomes of anaphylaxis-associated out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: Understanding the epidemiological characteristics of anaphylaxis
      associated out-of-hospital cardiac arrest (OHCA) is the first step toward
      developing preventative strategies and optimizing care systems. We aimed to
      describe and compare epidemiological features and clinical outcomes among
      patients with anaphylaxis-associated OHCAs according to causative agent groups.
      METHODS: We identified emergency medical service (EMS)-treated anaphylaxis
      associated OHCA patients from a nationwide OHCA registry between 2008 and 2015.
      We compared epidemiological characteristics and outcomes according to causal
      agents (a natural agents group and an iatrogenic agents group) and evaluated
      temporal variability in incidence. Multivariate logistic regression analysis was
      performed to compare survival to discharge between causative agent groups.
      RESULTS: During the study period (8 years), the total number of anaphylaxis
      associated OHCAs was 233. A total of 224 eligible cases were included in the
      analysis. There were 192 patients (85.6%) in the natural agents group and 32
      patients (14.3%) in the iatrogenic agents group. There was significant diurnal
      and seasonal variability in the frequency of anaphylaxis-associated OHCAs (p
      values<0.01 for both), with the highest incidences occurring during the day (7:01
      am to 3 pm; 64.6%) and in summer (June to August, 48.7%). Compared with the
      natural agents group, the adjusted odds ratio (AOR) for survival to discharge in
      the iatrogenic agents group was statistically insignificant (AOR 3.61, 95% CI
      0.86 to 15.06). CONCLUSION: The incidence of anaphylaxis-associated OHCA is
      considerably low, and significant temporal variability, with a peak during the
      day and in summer, is evident. Anaphylaxis-associated OHCA is more common by
      natural agents than by iatrogenic agents, but no difference in the survival-to
      discharge rate is evident.

PMID- 29579131
TI  - Cost-effectiveness of breast cancer screening using mammography in Vietnamese
      women.
AB  - BACKGROUND: The incidence rate of breast cancer is increasing and has become the
      most common cancer in Vietnamese women while the survival rate is lower than that
      of developed countries. Early detection to improve breast cancer survival as well
      as reducing risk factors remains the cornerstone of breast cancer control
      according to the World Health Organization (WHO). This study aims to evaluate the
      costs and outcomes of introducing a mammography screening program for Vietnamese
      women aged 45-64 years, compared to the current situation of no screening.
      METHODS: Decision analytical modeling using Markov chain analysis was used to
      estimate costs and health outcomes over a lifetime horizon. Model inputs were
      derived from published literature and the results were reported as incremental
      cost-effectiveness ratios (ICERs) and/or incremental net monetary benefits
      (INMBs). One-way sensitivity analyses and probabilistic sensitivity analyses were
      performed to assess parameter uncertainty. RESULTS: The ICER per life year gained
      of the first round of mammography screening was US$3647.06 and US$4405.44 for
      women aged 50-54 years and 55-59 years, respectively. In probabilistic
      sensitivity analyses, mammography screening in the 50-54 age group and the 55-59
      age group were cost-effective in 100% of cases at a threshold of three times the
      Vietnamese Gross Domestic Product (GDP) i.e., US$6332.70. However, less than 50%
      of the cases in the 60-64 age group and 0% of the cases in the 45-49 age group
      were cost effective at the WHO threshold. The ICERs were sensitive to the
      discount rate, mammography sensitivity, and transition probability from remission
      to distant recurrence in stage II for all age groups. CONCLUSION: From the
      healthcare payer viewpoint, offering the first round of mammography screening to
      Vietnamese women aged 50-59 years should be considered, with the given threshold
      of three times the Vietnamese GDP per capita.

PMID- 29579132
TI  - Implementation of a seven-day hospitalist program to improve the outcomes of the
      weekend admission: A retrospective before-after study in Taiwan.
AB  - OBJECTIVE: Patients admitted during weekends may have worse outcomes than those
      during weekdays. Adjusting the practice of senior physicians over weekends may
      reduce the weekend effect. DESIGN: A controlled before-after study, with
      propensity score matching (PSM) for potential confounding variables, to compare
      outcomes between weekday and weekend admissions. SETTING: A 2000-bed medical
      centre in Taiwan. PARTICIPANTS: Hospitalised general medicine patients cared for
      by traditional internal medicine teams (pre-intervention cohort) and those cared
      for by hospitalists after introducing a seven-day hospitalist program in the
      first six-month (post-intervention cohort) and following three-year periods. MAIN
      OUTCOME MEASURES: Proportion of intensive care unit (ICU) admissions,
      cardiopulmonary resuscitation (CPR) events, and in-hospital mortality. RESULTS:
      The pre-intervention cohort included 982 patients. Significantly higher mortality
      rates (11.3% vs. 6.2%, p = 0.032) were recorded in the case of weekend
      admissions, with similar proportions of ICU admission and CPR events. The post
      intervention cohort included 601 patients. No significant difference was recorded
      in any of the main outcomes between weekday and weekend admissions. PSM for pre
      intervention and post-intervention cohort showed shorter LOS after intervention,
      with no difference in ICU admission, CPR, and morality for the weekday and
      weekend admissions, respectively. The three-year cohort that followed, consisting
      of 3315 patients, showed no difference of outcomes between weekday and weekend
      admissions. After PSM, there were no significant differences in ICU admission
      rates (1.0% vs. 1.8%), CPR (0.3% vs. 0.2%) events and hospital mortality rates
      (8.1% vs. 8.5%), when weekday and weekend admissions were compared. CONCLUSIONS:
      The seven-day hospitalist program shows potential in providing equally safe care
      for both weekday and weekend general medicine admissions with sustainable
      development.

PMID- 29579133
TI  - Preparation, characterisation and antioxidant activities of rutin-loaded zein
      sodium caseinate nanoparticles.
AB  - Novel rutin-loaded zein-sodium caseinate nanoparticles (ZP) with antioxidant
      activity in aqueous medium were investigated. The results showed that the sodium
      caseinate concentrations, dosages of rutin and ethanol volume fractions
      significantly affected the zein nanoparticles' characteristics. Concerning the
      antioxidant properties, the highest values of rutin loaded ZP obtained using 2, 2
      diphenyl-1-picrylhydrazyl scavenging and 2 and 2'-azino-bis (3
      ethylbenzothiazoline-6-sulphonic acid) decolourisation assays were 52.7% and
      71.2%, respectively, and the total antioxidant capacity was 0.40 nmol g-1. The
      results suggest that zein-sodium caseinate nanoparticles can be used as a new
      nano carrier system for rutin or other water insoluble active ingredients.

PMID- 29579134
TI  - Correction: Women's reproductive health knowledge, attitudes and practices in
      relation to the Zika virus outbreak in northeast Brazil.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190024.].

PMID- 29579136
TI  - Impact of Diagnosis Threat on Neuropsychological Assessment of People with
      Acquired Brain Injury: Evidence of Mediation by Negative Emotions.
AB  - Objective: Some studies have shown that diagnosis threat (DT) could negatively
      impact the cognitive performance of undergraduate students who had sustained a
      mild traumatic brain injury. This study was designed to examine DT in people with
      acquired brain injury (ABI). As a second goal, we investigated the effect of
      stereotype lift as a way to overcome DT's harmful impact. The purpose of this
      study was also to examine the mechanisms mediating stereotype effects. Method:
      People with ABI and control participants were assigned to one of three
      conditions: DT, cognitive-neutral (in which the cognitive status of participants
      with ABI and the cognitive characteristics of the tasks were deemphasized), and
      stereotype lift (in which a downward comparison was made with another
      neurological group). Participants then completed neuropsychological tasks.
      Negative emotions, intrusive thoughts, task expectancy, and self-efficacy were
      assessed for mediation analyses. Results: Instructions impacted the performance
      of people with ABI, but not control participants. Compared to the cognitive
      neutral condition, participants with ABI in the DT condition performed worse on
      memory and executive tasks (but not on attention tasks). These effects were
      mediated by negative emotions. There was no increase in performance in the
      stereotype lift condition compared to the DT condition. Conclusions: This study
      showed that DT can aggravate the cognitive difficulties of people with ABI during
      neuropsychological assessment. The mediating role of negative emotions and the
      selective impact of DT on tasks that rely heavily on executive functioning are
      discussed in the light of the stereotype threat model.

PMID- 29579135
TI  - Observed Differences between Males and Females in Surgically Treated Carpal
      Tunnel Syndrome Among Non-manual Workers: A Sensitivity Analysis of Findings from
      a Large Population Study.
AB  - Objectives: We aimed at assessing whether differences among males and females in
      carpal tunnel syndrome (CTS) epidemiology might be attributable to segregation
      with respect to occupational biomechanical exposures or differential access to
      care by sex. Methods: We analysed surgically treated cases of CTS occurring among
      non-manual workers in Tuscany between 1997 and 2000. We conducted a Monte Carlo
      simulation to estimate the difference in occupational biomechanical exposures
      between males and females necessary to explain the observed incidence rate
      ratios. We also accounted for the sex-specific probability of receiving surgery
      after the diagnosis of CTS, as women were reported to be more likely to undergo
      surgery in a subset of our study population. We quantified the hypothetical
      biomechanical overload through the hand activity level (HAL) metric proposed by
      the American Conference of Governmental Industrial Hygienists. To quantify the
      effect of HAL on CTS risk, we assumed a prior distribution based on findings from
      two large cohort studies of industrial workers. Results: After adjustment for the
      probability of receiving surgery, women showed a 4-fold incidence of CTS as
      compared with men. To explain this association among non-manual workers, women
      should have an average value of HAL at least 5 points higher. Conclusions: Our
      analysis does not support the hypothesis that the difference in CTS incidence
      between males and females is entirely attributable to occupational risk factors
      or to differential access to surgery. The causal pathway between sex and CTS
      might include more determinants such as hormonal factors, anthropometric
      characteristics, and non-occupational exposure to biomechanical overload (e.g.
      household tasks).

PMID- 29579137
TI  - Trail-Making Test Part B: Evaluation of the Efficiency Score for Assessing Floor
      Level Change in Veterans.
AB  - Objective: The Trail Making Test - Part B (TMT-B) is a commonly used executive
      control measure with a known floor effect, limiting the ability to distinguish
      impairment among individuals unable to complete this task in the standard time
      limit. Our group previously proposed the TMT-B Efficiency Score (TMT-Be), which
      captures performance variability among examinees who fail to complete the task.
      The present study assesses the TMT-Be in a longitudinal clinical sample. Method:
      Data were collected via record review of veterans who underwent two clinical
      neuropsychological evaluations. We identified 30 veterans (mean age Visit 1:69 +/
      8.7 years) who were unable to complete TMT-B during at least one evaluation
      (mean days between visits = 615). Two scoring systems were utilized to examine
      performance variability: TMT-Be and TMT-B Prorated Score (TMT-Bpr). Results: TMT
      Be distribution was less skewed, but more platykuric, compared to TMT-Bpr. TMT-Be
      and TMT-Bpr were highly correlated. Both metrics correlated with psychomotor
      speed and another executive task, but not confrontation naming, providing both
      convergent and discriminant evidence of validity. TMT-Be, but not TMT-Bpr,
      detected significant decline in performance longitudinally. Age and education
      were significant predictors of the TMT-Be, but not TMT-Bpr, difference scores.
      Conclusions: Both metrics captured performance variability in a clinical sample
      and provided sufficient variance for examining floor-level performance on the TMT
      B. TMT-Be appeared to be less prone to creating outliers and more likely to
      detect change. The results support the utility of the TMT-Be metric in research
      and clinical settings.

PMID- 29579138
TI  - Breast Shape Analysis With Curvature Estimates and Principal Component Analysis
      for Cosmetic and Reconstructive Breast Surgery.
AB  - Background: Breast shape is defined utilizing mainly qualitative assessment
      (full, flat, ptotic) or estimates, such as volume or distances between reference
      points, that cannot describe it reliably. Objectives: We will quantitatively
      describe breast shape with two parameters derived from a statistical methodology
      denominated principal component analysis (PCA). Methods: We created a
      heterogeneous dataset of breast shapes acquired with a commercial infrared 3
      dimensional scanner on which PCA was performed. We plotted on a Cartesian plane
      the two highest values of PCA for each breast (principal components 1 and 2).
      Testing of the methodology on a preoperative and postoperative surgical case and
      test-retest was performed by two operators. Results: The first two principal
      components derived from PCA are able to characterize the shape of the breast
      included in the dataset. The test-retest demonstrated that different operators
      are able to obtain very similar values of PCA. The system is also able to
      identify major changes in the preoperative and postoperative stages of a two
      stage reconstruction. Even minor changes were correctly detected by the system.
      Conclusions: This methodology can reliably describe the shape of a breast. An
      expert operator and a newly trained operator can reach similar results in a
      test/re-testing validation. Once developed and after further validation, this
      methodology could be employed as a good tool for outcome evaluation, auditing,
      and benchmarking.

PMID- 29579140
TI  - Significance of whole-genome duplications on the emergence of evolutionary
      novelties.
AB  - Acquisition of evolutionary novelties is a fundamental process for adapting to
      the external environment and invading new niches and results in the
      diversification of life, which we can see in the world today. How such novel
      phenotypic traits are acquired in the course of evolution and are built up in
      developing embryos has been a central question in biology. Whole-genome
      duplication (WGD) is a process of genome doubling that supplies raw genetic
      materials and increases genome complexity. Recently, it has been gradually
      revealed that WGD and subsequent fate changes of duplicated genes can facilitate
      phenotypic evolution. Here, we review the current understanding of the
      relationship between WGD and the acquisition of evolutionary novelties. We show
      some examples of this link and discuss how WGD and subsequent duplicated genes
      can facilitate phenotypic evolution as well as when such genomic doubling can be
      advantageous for adaptation.

PMID- 29579139
TI  - Methanol induces cytosolic calcium variations, membrane depolarization and
      ethylene production in arabidopsis and tobacco.
AB  - Background and Aims: Methanol is a volatile organic compound released from plants
      through the action of pectin methylesterases (PMEs), which demethylesterify cell
      wall pectins. Plant PMEs play a role in developmental processes but also in
      responses to herbivory and infection by fungal or bacterial pathogens. However,
      molecular mechanisms that explain how methanol could affect plant defences remain
      poorly understood. Methods: Using cultured cells and seedlings from Arabidopsis
      thaliana and tobacco BY2 expressing the apoaequorin gene, allowing quantification
      of cytosolic Ca2+, a reactive oxygen species (ROS) probe (CLA, Cypridina
      luciferin analogue) and electrophysiological techniques, we followed early plant
      cell responses to exogenously supplied methanol applied as a liquid or as
      volatile. Key Results: Methanol induces cytosolic Ca2+ variations that involve
      Ca2+ influx through the plasma membrane and Ca2+ release from internal stores.
      Our data further suggest that these Ca2+ variations could interact with different
      ROS and support a signalling pathway leading to well known plant responses to
      pathogens such as plasma membrane depolarization through anion channel regulation
      and ethylene synthesis. Conclusions: Methanol is not only a by-product of PME
      activities, and our data suggest that [Ca2+]cyt variations could participate in
      signalling processes induced by methanol upstream of plant defence responses.

PMID- 29579141
TI  - Where to search top-K biomedical ontologies?
AB  - Motivation: Searching for precise terms and terminological definitions in the
      biomedical data space is problematic, as researchers find overlapping, closely
      related and even equivalent concepts in a single or multiple ontologies. Search
      engines that retrieve ontological resources often suggest an extensive list of
      search results for a given input term, which leads to the tedious task of
      selecting the best-fit ontological resource (class or property) for the input
      term and reduces user confidence in the retrieval engines. A systematic
      evaluation of these search engines is necessary to understand their strengths and
      weaknesses in different search requirements. Result: We have implemented seven
      comparable Information Retrieval ranking algorithms to search through ontologies
      and compared them against four search engines for ontologies. Free-text queries
      have been performed, the outcomes have been judged by experts and the ranking
      algorithms and search engines have been evaluated against the expert-based ground
      truth (GT). In addition, we propose a probabilistic GT that is developed
      automatically to provide deeper insights and confidence to the expert-based GT as
      well as evaluating a broader range of search queries. Conclusion: The main
      outcome of this work is the identification of key search factors for biomedical
      ontologies together with search requirements and a set of recommendations that
      will help biomedical experts and ontology engineers to select the best-suited
      retrieval mechanism in their search scenarios. We expect that this evaluation
      will allow researchers and practitioners to apply the current search techniques
      more reliably and that it will help them to select the right solution for their
      daily work. Availability: The source code (of seven ranking algorithms), ground
      truths and experimental results are available at
      https://github.com/danielapoliveira/bioont-search-benchmark.

PMID- 29579143
TI  - Effort Testing in Dementia Assessment: A Systematic Review.
AB  - Objective: Interpretation of neuropsychological test data is only valid when
      appropriate effort has been exerted. Research, however, suggests that
      neuropsychologists do not always formally test for effort and that this may
      especially be the case in the context of dementia assessment. This review
      systematically examined the literature that has investigated the use of both
      purpose-built and embedded effort-sensitive indices in dementia, mild cognitive
      impairment (MCI), and healthy control samples. The aim was to determine which
      tests of effort are most sensitive to suboptimal effort and least sensitive to
      the type of cognitive impairment seen in dementia. Methods: A systematic search
      of databases was conducted to October 2017. There was no start date. Results:
      Twenty-five studies were included for review. The studies were divided into two
      categories according to methodology. One category of studies (n = 5) was reviewed
      using a tailored methodological quality rating checklist whilst the remaining
      studies (n = 20) were reviewed using the Crowe Critical Appraisal Tool (CCAT).
      Conclusions: The results of this review suggest that PVTs which take a
      hierarchical approach to effort testing such as the WMT, MSVT, and NV-MSVT are
      preferable for use with older adults who are under investigation for possible
      dementia. These tests go above and beyond the traditional pass/fail approach of
      more traditional tests of effort because they allow the examiner to analyze the
      examinee's profile of scores. The methodological limitations and challenges
      involved in this field of research are discussed.

PMID- 29579144
TI  - Gender and Ageing at Work in Chile: Employment, Working Conditions, Work-Life
      Balance and Health of Men and Women in an Ageing Workforce.
AB  - Objectives: In Chile, working after retirement age has grown substantially over
      the last years. This, in addition to the country's current discussion about
      extending retirement age, motivates the need of generating evidence on the
      occupational health and safety of the working old, with a special focus on women,
      who are critically disadvantaged in Chile's labour market. The objective of this
      paper is to describe and compare the ageing workforce of women and men in Chile
      in terms of labour market participation, employment and working conditions, work
      life balance, and health. The social determinants of health and employment
      sustainability frameworks guide this study. Data Sources: Cross-sectional data
      from three publicly available sources: the Chilean Labour Force Survey, NENE
      (2010); the first Chilean Employment and working conditions survey, ENETS (2009
      2010) and the second National Health Survey, ENS (2009). Methods: Participation
      rates and employment conditions (NENE and ENETS), working conditions,
      occupational health and work-life balance (ENETS) and chronic health conditions
      (ENS) were described by 5-year age groups separately for women and men.
      Descriptions cover all age groups in order to identify trends and patterns
      characteristic of older workers. Results: Rates of occupation decrease sharply
      after age 54 in women and 59 in men. Ageing women and men who continue to work
      are more likely to be in own-account (self-employed) work than younger workers;
      in the case of women, in households as domestic workers, and men, in agriculture.
      Social protection and workplace rights are markedly reduced in older workers.
      Part-time work increases from the age of 50 onwards, especially among women, but
      average working hours do not decrease under 30 h a week for either women or men.
      Interestingly, between ages 60 and 64, there is a peak increase of day and night
      shift-work among women, which co-occurs with a peak in domestic work, possibly
      corresponding to women working as caretakers of elderly people. Several workplace
      risks continue to be high into old age: intensive work and demanding physical
      work, especially in men, and the combination of paid and unpaid care work in
      women, which continues to be high up to the age of 70 years. The health of older
      workers is better than that of non-working people of the same age, a gap which is
      markedly larger for women than men and tends to increase among women as they age.
      Conclusion: Results indicate that Chileans working into old age face precarious
      jobs with limited protection and several adverse working conditions. Noteworthy,
      women carry the double burden of paid and unpaid work into their late years. In
      addition, results suggest they are affected more profoundly by the healthy worker
      effect whereby the health condition determines the probability of finding and
      keeping a job-also known as a health selection mechanism-which increases as they
      age. These employment and working conditions indicate that working into old age
      is not yet sustainable in Chile and counts as evidence that needs to be taken
      into account in discussions about delaying the retirement age in the country, as
      well as incorporating support systems to alleviate the double work burden of
      ageing working women.

PMID- 29579142
TI  - The Assessment of Pain in Older People: UK National Guidelines.

PMID- 29579146
TI  - The application of CRISPR-Cas9 genome editing tool in cancer immunotherapy.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-associated
      protein 9 (CRISPR-Cas9) system was originally discovered in prokaryotes
      functioned as a part of the adaptive immune system. Because of its high
      efficiency and easy operability, CRISPR-Cas9 system has been developed to be a
      powerful and versatile gene editing tool shortly after its discovery. Given that
      multiple genetic alterations are the main factors that drive genesis and
      development of tumor, CRISPR-Cas9 system has been applied to correct cancer
      causing gene mutations and deletions and to engineer immune cells, such as
      chimeric antigen receptor T (CAR T) cells, for cancer immunotherapeutic
      applications. Recently, CRISPR-Cas9-based CAR T-cell preparation has been an
      important breakthrough in antitumor therapy. Here, we summarize the mechanism,
      delivery and the application of CRISPR-Cas9 in gene editing, and discuss the
      challenges and future directions of CRISPR-Cas9 in cancer immunotherapy.

PMID- 29579147
TI  - Cas9/sgRNA-based genome editing and other reverse genetic approaches for
      functional genomic studies in rice.
AB  - One of the important and direct ways of investigating the function of a gene is
      to characterize the phenotypic consequences associated with loss or gain-of
      function of the corresponding gene. These mutagenesis strategies have been
      successfully deployed in Arabidopsis, and subsequently extended to crop species
      including rice. Researchers have made vast advancements in the area of rice
      genomics and functional genomics, as it is a diploid plant with a relatively
      smaller genome size unlike other cereals. The advent of rice genome research and
      the annotation of high-quality genome sequencing along with the developments in
      databases and computer searches have enabled the functional characterization of
      unknown genes in rice. Further, with the improvements in the efficiency of
      regeneration and transformation protocols, it has now become feasible to produce
      sizable mutant populations in indica rice varieties also. In this review, various
      mutagenesis methods, the current status of the mutant resources, limitations and
      strengths of insertional mutagenesis approaches and also results obtained with
      suitable screens for stress tolerance in rice are discussed. In addition,
      targeted genome editing using clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) or Cas9/single-guide RNA
      system and its potential applications in generating transgene-free rice plants
      through genome engineering as an efficient alternative to classical transgenic
      technology are also discussed.

PMID- 29579148
TI  - Reduced Pain and Accelerated Recovery Following Primary Breast Augmentation With
      Lightweight Breast Implants.
AB  - Background: The posttreatment pain associated with breast augmentation is a top
      concern of most patients and can affect the decision concerning surgery.
      Objectives: This study aimed to compare the posttreatment pain and recovery times
      of patients undergoing primary breast augmentation with lightweight vs full-mass
      implants of similar volumes. The authors hypothesized that the reduced mechanical
      strain applied by lightweight implants elicits less pain. Methods: In this
      retrospective, observational study, 100 women who had undergone primary breast
      augmentation with either a lightweight breast implant or a traditional full-mass
      silicone implant (n = 50), were contacted by phone and asked about their
      posttreatment experiences and overall satisfaction with the outcome. All women
      were treated by the same surgical team, and the two groups were matched by date
      of surgery. Results: Most patients in the two cohorts had a self-reported
      preoperative B cup size and relatively high tolerance to pain. On average, LWBI
      patients were 6 years older than those undergoing full-mass implantation (32.4 +/
      8.7 vs 26.2 +/- 8.0; P = .0004) and more had experienced at least one pregnancy
      (61.2% vs 24%, P = .0002). LWBI patients opted for implants 39 +/- 28.4 cc larger
      than patients in the control group. Subglandular placement was selected in most
      cases (LWBI: 83.7% and full-mass: 90.0%). Mean posttreatment pain was lower in
      the LWBI cohort (5.5 +/- 2.4 vs 6.5 +/- 2.4) and required a shorter duration of
      analgesics (3.87 +/- 1.77 days vs 5.26 +/- 2.94 days; P = .009). Age- and parity
      adjusted measures demonstrated a respective 2-day and 5-day shorter recovery
      period and return to normal activities interval in the LWBI versus full-mass
      implant cohorts (P = .04 and P = .002, respectively). Conclusions: As compared to
      traditional silicone filled full-mass implants, breast augmentations with B-Lite
      lightweight breast implants (G&G Biotechnology Ltd., Haifa, Israel) elicit less
      posttreatment pain and require less down-time, ultimately, meeting patients'
      quest for desired breast shape at minimal discomfort. Level of Evidence 3: 

PMID- 29579145
TI  - Quantitative single-cell transcriptomics.
AB  - Single-cell RNA sequencing (scRNA-seq) is currently transforming our
      understanding of biology, as it is a powerful tool to resolve cellular
      heterogeneity and molecular networks. Over 50 protocols have been developed in
      recent years and also data processing and analyzes tools are evolving fast. Here,
      we review the basic principles underlying the different experimental protocols
      and how to benchmark them. We also review and compare the essential methods to
      process scRNA-seq data from mapping, filtering, normalization and batch
      corrections to basic differential expression analysis. We hope that this helps to
      choose appropriate experimental and computational methods for the research
      question at hand.

PMID- 29579149
TI  - Genetic differentiation in cauline-leaf-specific wettability of a rosette-forming
      perennial Arabidopsis from two contrasting montane habitats.
AB  - Background and Aims: An altitudinal gradient of leaf wettability is often
      observed between and within species. To understand its functional significance,
      positional variation of leaf surfaces within plants should be taken into account.
      In rosette-forming plants, rosette leaves are near the ground and their adaxial
      surfaces are exposed, whereas cauline leaves are lifted from the ground
      throughout the reproductive season, and their abaxial surfaces are more exposed.
      Here, we investigated leaf wettability of cauline and rosette leaves of
      Arabidopsis halleri subsp. gemmifera growing in contrasting montane habitats
      along an altitudinal gradient at Mt Ibuki, Japan. Methods: We conducted field
      investigations and a growth chamber experiment to determine whether field
      observed variation in leaf wettability was caused by genetic differentiation. We
      further performed gene expression analysis of a wax-related gene, i.e. AhgCER1, a
      homologue of A. thaliana ECERIFERUM1 (CER1) that may be involved in
      differentiation of leaf wettability. Key Results: We found cauline-leaf specific
      genetic differentiation in leaf wettability between contrasting montane habitats.
      Cauline leaves of semi-alpine plants, especially on abaxial surfaces, were non
      wettable. Cauline leaves of low-altitudinal understorey plants were wettable, and
      rosette leaves were also wettable in both habitats. AhgCER1 expression
      corresponded to observed leaf wettability patterns. Conclusions: Low wettability
      of cauline leaves is hypothesized to keep exposed surfaces dry when they are
      wrapping flowering buds in early spring, and presumably protects flowering buds
      from frost damage. The genetic system that controls wax content, specifically for
      cauline leaves, should be involved in the observed genetic differentiation, and
      AhgCER1 control is a strong candidate for the underlying genetic mechanism.

PMID- 29579150
TI  - Dietary fat is a key determinant in balancing mitochondrial dynamics in heart
      failure: a novel mechanism underlying the obesity paradox.

PMID- 29579151
TI  - Contrasting plant height can improve the control of rain-borne diseases in wheat
      cultivar mixture: modelling splash dispersal in 3-D canopies.
AB  - Background and Aims: Growing cultivars differing by their disease resistance
      level together (cultivar mixtures) can reduce the propagation of diseases.
      Although architectural characteristics of cultivars are little considered in
      mixture design, they could have an effect on disease, in particular through spore
      dispersal by rain splash, which occurs over short distances. The objective of
      this work was to assess the impact of plant height of wheat cultivars in mixtures
      on splash dispersal of Zymoseptoria tritici, which causes septoria tritici leaf
      blotch. Methods: We used a modelling approach involving an explicit description
      of canopy architecture and splash dispersal processes. The dispersal model
      computed raindrop interception by a virtual canopy as well as the production,
      transport and interception of splash droplets carrying inoculum. We designed 3-D
      virtual canopies composed of susceptible and resistant plants, according to field
      measurements at the flowering stage. In numerical experiments, we tested
      different heights of virtual cultivars making up binary mixtures to assess the
      influence of this architectural trait on dispersal patterns of spore-carrying
      droplets. Key Results: Inoculum interception decreased exponentially with the
      height relative to the main inoculum source (lower diseased leaves of susceptible
      plants), and little inoculum was intercepted further than 40 cm above the
      inoculum source. Consequently, tall plants intercepted less inoculum than smaller
      ones. Plants with twice the standard height intercepted 33 % less inoculum than
      standard height plants. In cases when the height of suscpeptible plants was
      doubled, inoculum interception by resistant leaves was 40 % higher. This physical
      barrier to spore-carrying droplet trajectories reduced inoculum interception by
      tall susceptible plants and was modulated by plant height differences between
      cultivars of a binary mixture. Conclusions: These results suggest that mixture
      effects on spore dispersal could be modulated by an adequate choice of
      architectural characteristics of cultivars. In particular, even small differences
      in plant height could reduce spore dispersal.

PMID- 29579152
TI  - Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde
      dehydrogenase 2.
AB  - Aims: We previously demonstrated that acute ethanol administration protects the
      heart from ischaemia/reperfusion (I/R) injury thorough activation of aldehyde
      dehydrogenase 2 (ALDH2). Here, we characterized the role of acetaldehyde, an
      intermediate product from ethanol metabolism, and its metabolizing enzyme, ALDH2,
      in an ex vivo model of cardiac I/R injury. Methods and results: We used a
      combination of homozygous knock-in mice (ALDH2*2), carrying the human
      inactivating point mutation ALDH2 (E487K), and a direct activator of ALDH2, Alda
      1, to investigate the cardiac effect of acetaldehyde. The ALDH2*2 mice have
      impaired acetaldehyde clearance, recapitulating the human phenotype. Yet, we
      found a similar infarct size in wild type (WT) and ALDH2*2 mice. Similar to
      ethanol-induced preconditioning, pre-treatment with 50 MUM acetaldehyde increased
      ALDH2 activity and reduced cardiac injury in hearts of WT mice without affecting
      cardiac acetaldehyde levels. However, acetaldehyde pre-treatment of hearts of
      ALDH2*2 mice resulted in a three-fold increase in cardiac acetaldehyde levels and
      exacerbated I/R injury. Therefore, exogenous acetaldehyde appears to have a
      bimodal effect in I/R, depending on the ALDH2 genotype. Further supporting an
      ALDH2 role in cardiac preconditioning, pharmacological ALDH2 inhibition abolished
      ethanol-induced cardioprotection in hearts of WT mice, whereas a selective
      activator, Alda-1, protected ALDH2*2 against ethanol-induced cardiotoxicity.
      Finally, either genetic or pharmacological inhibition of ALDH2 mitigated
      ischaemic preconditioning. Conclusion: Taken together, our findings suggest that
      low levels of acetaldehyde are cardioprotective whereas high levels are damaging
      in an ex vivo model of I/R injury and that ALDH2 is a major, but not the only,
      regulator of cardiac acetaldehyde levels and protection from I/R.

PMID- 29579153
TI  - iterClust: a statistical framework for iterative clustering analysis.
AB  - Motivation: In a scenario where populations A, B1 and B2 (subpopulations of B)
      exist, pronounced differences between A and B may mask subtle differences between
      B1 and B2. Results: Here we present iterClust, an iterative clustering framework,
      which can separate more pronounced differences (e.g. A and B) in starting
      iterations, followed by relatively subtle differences (e.g. B1 and B2), providing
      a comprehensive clustering trajectory. Availability and implementation: iterClust
      is implemented as a Bioconductor R package. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29579155
TI  - A polymorphism in the lysyl oxidase propeptide domain accelerates carcinogen
      induced cancer.
AB  - The propeptide (LOX-PP) domain of the lysyl oxidase proenzyme was shown to
      inhibit the transformed phenotype of breast, lung and pancreatic cells in culture
      and the formation of Her2/neu-driven breast cancer in a xenograft model. A single
      nucleotide polymorphism (SNP, rs1800449) positioned in a highly conserved region
      of LOX-PP results in an Arg158Gln substitution (humans). This arginine (Arg)
      >glutamine (Gln) substitution profoundly impaired the ability of LOX-PP to
      inhibit the invasive phenotype and xenograft tumor formation. To study the effect
      of the SNP in vivo, here we established a knock in (KI) mouse line (LOX-PPGln
      mice) expressing an Arg152Gln substitution corresponding to the human Arg158Gln
      polymorphism. Breast cancer was induced in wild-type (WT) and LOX-PPGln female
      mice beginning at 6 weeks of age by treatment with 7,12-dimethylbenz(a)anthracene
      (DMBA) in combination with progesterone. Time course analysis of tumor
      development demonstrated earlier tumor onset and shorter overall survival in LOX
      PPGln versus WT mice. To further compare the tumor burden in WT and LOX-PPGln
      mice, inguinal mammary glands from both groups of mice were examined for
      microscopic lesion formation. LOX-PPGln glands contained more lesions (9.6 versus
      6.9 lesions/#4 bilateral). In addition, more DMBA-treated LOX-PPGln mice had
      increased leukocyte infiltrations in their livers and were moribund compared with
      DMBA-treated WT mice. Thus, these data indicate that the Arg->Gln substitution in
      LOX-PP could be an important marker associated with a more aggressive cancer
      phenotype and that this KI model is ideal for further mechanistic studies
      regarding the tumor suppressor function of LOX-PP.

PMID- 29579154
TI  - Specification of trophoblast from embryonic stem cells exposed to BMP4.
AB  - Trophoblast (TB) comprises the outer cell layers of the mammalian placenta that
      make direct contact with the maternal uterus and, in species with a highly
      invasive placenta, maternal blood. It has its origin as trophectoderm, a single
      epithelial layer of extra-embryonic ectoderm that surrounds the embryo proper at
      the blastocyst stage of development. Here, we briefly compare the features of TB
      specification and determination in the mouse and the human. We then review
      research on a model system that has been increasingly employed to study TB
      emergence, namely the BMP4 (bone morphogenetic protein-4)-directed
      differentiation of human embryonic stem cells (ESCd), and discuss why outcomes
      using it have proved so uneven. We also examine the controversial aspects of this
      model, particularly the issue of whether or not the ESCd represents TB at all.
      Our focus here has been to explore similarities and potential differences between
      the phenotypes of ESCd, trophectoderm, placental villous TB, and human TB stem
      cells. We then explore the role of BMP4 in the differentiation of human
      pluripotent cells to TB and suggest that it converts the ESC into a totipotent
      state that is primed for TB differentiation when self-renewal is blocked. Finally
      we speculate that the TB formed from ESC is homologous to the trophectoderm
      derived, invasive TB that envelopes the implanting conceptus during the second
      week of pregnancy.

PMID- 29579156
TI  - CEP55 promotes the proliferation and invasion of tumour cells via the AKT
      signalling pathway in osteosarcoma.
AB  - The molecular mechanisms underlying the development of osteosarcoma (OS) are not
      fully understood. In this study, we investigated for the first time the clinical
      significance and biological activity of centrosomal protein 55 (CEP55) in OS. We
      found that CEP55 was overexpressed in OS, and the CEP55 expression level in OS
      was correlated with metastasis and poor prognosis. Through in vitro experiments,
      we confirmed that CEP55 knockdown significantly induced cell cycle arrest at G1
      phase and suppressed OS cell proliferation, migration and invasion. In addition,
      CEP55 knockdown suppressed OS tumour growth in nude mice. Global gene expression
      profiling of CEP55-silenced MNNG/HOS cells showed that the AKT pathway might be
      involved in the regulation of OS cell activity. Two downstream factors of AKT
      signalling, CCND1 and FN1, were found to have significantly higher expression in
      tumour tissues, and their mRNA expression levels were strongly correlated with
      CEP55 expression. To conclude, our data suggest that CEP55 can be used as a
      prognostic marker for OS, highlighting the significance of CEP55 signalling as a
      putative therapeutic target.

PMID- 29579157
TI  - Cellular prion protein is involved in decidualization of mouse uterus.
AB  - Prion protein (PrP) is encoded by a single copy gene Prnp in many cell and tissue
      types. PrP is very famous for its infectious conformers (PrPSC) resulting in
      transmissible spongiform encephalopathies. At present, physiological functions of
      its cellular isoform (PrPC) remain ambiguous. Although PrPC expression has been
      found in uterus, whether it functions in maternal-fetal dialogue during early
      pregnant is unknown. In this study, we examined PrPC mRNA and protein in the
      uterus of peri-implantation mice, and found that they were expressed with a
      spatiotemporal dynamic pattern. Interestingly, PrPC was significantly increased
      in the decidual zones around the implanting embryos at the implantation window
      stage. To further demonstrate that PrPC is involved in the decidualization of
      mouse uterus during embryo implantation, we constructed the artificial
      decidualization models and the delayed implantation models. Once the
      pseudopregnant mice were artificially induced to decidualization, the PrPC
      expression then increased significantly in the decidua zone. And also, if the
      delayed implantation embryos were allowed to implant, PrPC protein was also
      simultaneously improved in stromal cells surrounding the implanting embryos.
      Moreover, PrPC expression can be inhibited by progesterone but upregulated by
      estrogen in mouse uterus. These results suggest that PrPC may play an important
      role in embryo implantation and decidualization.

PMID- 29579158
TI  - Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A
      Randomized Controlled Trial.
AB  - Background: BCG vaccine may reduce overall mortality by increasing resistance to
      nontuberculosis infections. In 2 randomized trials in Guinea-Bissau of early BCG
      Denmark (Statens Serum Institut) given to low-weight (LW) neonates (<2500 g at
      inclusion) to reduce infant mortality rates, we observed a very beneficial effect
      in the neonatal period. We therefore conducted the present trial to test whether
      early BCG-Denmark reduces neonatal mortality by 45%. We also conducted a meta
      analysis of the 3 BCG-Denmark trials. Methods: In 2008-2013, we randomized LW
      neonates to "early BCG-Denmark" (intervention group; n = 2083) or "control"
      (local policy for LW and no BCG-Denmark; n = 2089) at discharge from the
      maternity ward or at first contact with the health center. The infants were
      randomized (1:1) without blinding in blocks of 24. Data was analyzed in Cox
      hazards models providing mortality rate ratios (MRRs). We had prespecified an
      analysis censoring follow-up at oral poliovirus vaccine campaigns. Results: Early
      administration of BCG-Denmark was associated with a nonsignificant reduction in
      neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47-1.04) and a
      34% reduction (0.66; .44-1.00) when censoring for oral poliovirus vaccine
      campaigns. There was no reduction in mortality rate for noninfectious diseases,
      but a 43% reduction in infectious disease mortality rate (MRR, 0.57; 95% CI, .35
      .93). A meta-analysis of 3 BCG trials showed that early BCG-Denmark reduced
      mortality by 38% (MRR, 0.62; 95% CI, .46-.83) within the neonatal period and 16%
      (0.84; .71-1.00) by age 12 months. Conclusion: Early administration of BCG
      Denmark in LW infants is associated with major reductions in mortality rate. It
      is important that all LW infants receive early BCG in areas with high neonatal
      mortality rates. Clinical Trials Registration: NCT00625482.

PMID- 29579159
TI  - Reactivation of the Nkx2.5 cardiac enhancer after myocardial infarction does not
      presage myogenesis.
AB  - Aims: The contribution of resident stem or progenitor cells to cardiomyocyte
      renewal after injury in adult mammalian hearts remains a matter of considerable
      debate. We evaluated a cell population in the adult mouse heart induced by
      myocardial infarction (MI) and characterized by an activated Nkx2.5 enhancer
      element that is specific for multipotent cardiac progenitor cells (CPCs) during
      embryonic development. We hypothesized that these MI-induced cells (MICs) harbour
      cardiomyogenic properties similar to their embryonic counterparts. Methods and
      results: MICs reside in the heart and mainly localize to the infarction area and
      border zone. Interestingly, gene expression profiling of purified MICs 1 week
      after infarction revealed increased expression of stem cell markers and embryonic
      cardiac transcription factors (TFs) in these cells as compared to the non-mycoyte
      cell fraction of adult hearts. A subsequent global transcriptome comparison with
      embryonic CPCs and fibroblasts and in vitro culture of MICs unveiled that (myo
      )fibroblastic features predominated and that cardiac TFs were only expressed at
      background levels. Conclusions: Adult injury-induced reactivation of a cardiac
      specific Nkx2.5 enhancer element known to specifically mark myocardial progenitor
      cells during embryonic development does not reflect hypothesized embryonic
      cardiomyogenic properties. Our data suggest a decreasing plasticity of cardiac
      progenitor (-like) cell populations with increasing age. A re-expression of
      embryonic, stem or progenitor cell features in the adult heart must be
      interpreted very carefully with respect to the definition of cardiac resident
      progenitor cells. Albeit, the abundance of scar formation after cardiac injury
      suggests a potential to target predestinated activated profibrotic cells to push
      them towards cardiomyogenic differentiation to improve regeneration.

PMID- 29579161
TI  - Orthostatic hypotension and cognitive function: cross-sectional results from the
      ELSA-Brasil study.
AB  - Background: The association between orthostatic hypotension (OH) and cognitive
      impairment is controversial, and most studies have investigated older white
      adults from Western Europe and the United States. Therefore, we investigated the
      association between OH and cognitive performance in a large and racially diverse
      sample of adults using cross-sectional data from the Brazilian Longitudinal Study
      of Adult Health (ELSA-Brasil). Methods: OH was defined when systolic blood
      pressures (SBP) decreased 20 mmHg and/or diastolic blood pressure (DBP) decreased
      10 mmHg from supine to standing position. We investigated the association between
      OH and composite global cognition, memory, verbal fluency (VF), and Trail Making
      test z-scores, using multiple linear regression models. We also investigated the
      association of orthostatic hypertension and SBP/DBP changes with cognitive
      performance, as well as the interaction between OH and compensatory heart rate
      (HR) after postural change on cognitive performance. Results: We evaluated 12,826
      participants (mean age=51.5+/-9.0 years, 46% male, 53% white). Participants with
      OH (4% of the sample) had poorer z-scores for VF (beta=-0.108, 95% CI=-0.189; 
      0.025, p=0.01) than participants without OH. Orthostatic hypertension was also
      associated with worse performance on the VF test (beta=-0.080, 95% CI=-0.157; 
      0.003, p=0.04). SBP orthostatic change had a non-linear association with VF. The
      interaction terms between OH and compensatory increase in HR for the Trail Making
      Test z-score (p=0.09) was borderline significant, suggesting that participants
      who lack compensatory HR after postural change might have poorer performance.
      Conclusion: OH and orthostatic hypertension were associated with poorer
      performance on the VF test in participants from Brazil.

PMID- 29579160
TI  - Data-driven models of dominantly-inherited Alzheimer's disease progression.
AB  - See Li and Donohue (doi:10.1093/brain/awy089) for a scientific commentary on this
      article.Dominantly-inherited Alzheimer's disease is widely hoped to hold the key
      to developing interventions for sporadic late onset Alzheimer's disease. We use
      emerging techniques in generative data-driven disease progression modelling to
      characterize dominantly-inherited Alzheimer's disease progression with
      unprecedented resolution, and without relying upon familial estimates of years
      until symptom onset. We retrospectively analysed biomarker data from the sixth
      data freeze of the Dominantly Inherited Alzheimer Network observational study,
      including measures of amyloid proteins and neurofibrillary tangles in the brain,
      regional brain volumes and cortical thicknesses, brain glucose hypometabolism,
      and cognitive performance from the Mini-Mental State Examination (all adjusted
      for age, years of education, sex, and head size, as appropriate). Data included
      338 participants with known mutation status (211 mutation carriers in three
      subtypes: 163 PSEN1, 17 PSEN2, and 31 APP) and a baseline visit (age 19-66; up to
      four visits each, 1.1 +/- 1.9 years in duration; spanning 30 years before, to 21
      years after, parental age of symptom onset). We used an event-based model to
      estimate sequences of biomarker changes from baseline data across disease
      subtypes (mutation groups), and a differential equation model to estimate
      biomarker trajectories from longitudinal data (up to 66 mutation carriers, all
      subtypes combined). The two models concur that biomarker abnormality proceeds as
      follows: amyloid deposition in cortical then subcortical regions (~24 +/- 11
      years before onset); phosphorylated tau (17 +/- 8 years), tau and amyloid-beta
      changes in cerebrospinal fluid; neurodegeneration first in the putamen and
      nucleus accumbens (up to 6 +/- 2 years); then cognitive decline (7 +/- 6 years),
      cerebral hypometabolism (4 +/- 4 years), and further regional neurodegeneration.
      Our models predicted symptom onset more accurately than predictions that used
      familial estimates: root mean squared error of 1.35 years versus 5.54 years. The
      models reveal hidden detail on dominantly-inherited Alzheimer's disease
      progression, as well as providing data-driven systems for fine-grained patient
      staging and prediction of symptom onset with great potential utility in clinical
      trials.

PMID- 29579162
TI  - Scutal Index and Its Role in Guiding Prophylaxis for Lyme Disease Following Tick
      Bite.

PMID- 29579163
TI  - Assessment of Duration of Tick Feeding by the Scutal Index Reduces Need for
      Antibiotic Prophylaxis After Ixodes scapularis Tick Bites.
AB  - Doxycycline is recommended for persons with Ixodes scapularis tick bites in
      certain geographic areas, if the tick had fed for at least 36 hours. Based on the
      scutal index, over 40% of I. scapularis tick bites from patients seen at the Lyme
      Disease Diagnostic Center did not warrant antibiotic prophylaxis.

PMID- 29579164
TI  - Daily Marital Tension and Symptom Severity in Older Adults With Diabetes or
      Osteoarthritis.
AB  - Background: Greater marital quality is associated with better psychological and
      physical health. The quality of daily marital interactions is likely to be
      especially important for individuals with chronic illness, but this question has
      received little attention. Purpose: Using data from two diary studies, the
      current study examined whether individuals with chronic illness would experience
      more severe symptoms on days with more marital tension due in part to greater
      negative affect on those days. Methods: The samples included individuals with
      knee osteoarthritis (OA, N = 145) or type 2 diabetes mellitus (T2DM, N = 129) and
      their spouses. Participants reported on daily marital interaction quality,
      affect, and symptom severity (patients only) for 22 days (knee OA) or 24 days
      (T2DM). Separate multilevel models were run for patients and spouses, controlling
      for the partner's marital tension and negative affect as well as both partners'
      daily marital enjoyment and positive affect. We examined same-day and across-day
      associations. Results: For individuals with T2DM or knee OA, more severe symptoms
      on days with more marital tension were due in part to their greater negative
      affect on those days. Individuals with knee OA who experienced more pain had more
      negative affect and marital tension the next day. Conclusions: Negative marital
      interactions may exacerbate physical symptoms. Effects of daily marital tension
      likely accumulate over time and have long-term implications for health.

PMID- 29579166
TI  - Echo-fluoro fusion imaging guidance for no contrast transfemoral aortic valve
      implantation.

PMID- 29579165
TI  - Integrating ChIP-seq with other functional genomics data.
AB  - Transcription is regulated by transcription factor (TF) binding at promoters and
      distal regulatory elements and histone modifications that control the
      accessibility of these elements. Chromatin immunoprecipitation followed by
      sequencing (ChIP-seq) has become the standard assay for identifying genome-wide
      protein-DNA interactions in vitro and in vivo. As large-scale ChIP-seq data sets
      have been collected for different TFs and histone modifications, their potential
      to predict gene expression can be used to test hypotheses about the mechanisms of
      gene regulation. In addition, complementary functional genomics assays provide a
      global view of chromatin accessibility and long-range cis-regulatory interactions
      that are being combined with TF binding and histone remodeling to study the
      regulation of gene expression. Thus, ChIP-seq analysis is now widely integrated
      with other functional genomics assays to better understand gene regulatory
      mechanisms. In this review, we discuss advances and challenges in integrating
      ChIP-seq data to identify context-specific chromatin states associated with gene
      activity. We describe the overall computational design of integrating ChIP-seq
      data with other functional genomics assays. We also discuss the challenges of
      extending these methods to low-input ChIP-seq assays and related single-cell
      assays.

PMID- 29579167
TI  - Glucocorticoid Receptor Signaling Is Not Required for In Vivo Adipogenesis.
AB  - Regulation of adipogenesis is of major interest given that adipose tissue
      expansion and dysfunction are central to metabolic syndrome. Glucocorticoids
      (GCs) are important for adipogenesis in vitro. However, establishing a role for
      GCs in adipogenesis in vivo has been difficult. GC receptor (GR)-null mice die at
      birth, a time at which wild-type (WT) mice do not have fully developed white
      adipose depots. We conducted several studies aimed at defining the role of GC
      signaling in adipogenesis in vitro and in vivo. First, we showed that GR-null
      mouse embryonic fibroblasts (MEFs) have compromised ability to form adipocytes in
      vitro, a phenotype that can be partially rescued with a peroxisome proliferator
      activated receptor gamma agonist. Next, we demonstrated that MEFs are capable of
      forming de novo fat pads in mice despite the absence of GR or circulating GCs [by
      bilateral adrenalectomy (ADX)]. However, ADX and GR-null fat pads and their
      associated adipocyte areas were smaller than those in controls. Second, using
      adipocyte-specific luciferase reporter mice, we identified adipocytes in both WT
      and GR-null embryonic day (E)18 mouse embryos. Lastly, positive perilipin
      staining in WT and GR-null E18 embryos confirmed the presence of early white
      inguinal and brown adipocytes. Taken together, these results provide compelling
      evidence that GCs and GR augment but are not required for the development of
      functional adipose tissue in vivo.

PMID- 29579169
TI  - Robotic double-sleeve resection of lung cancer: technical aspects.
AB  - For centrally located lung cancer invading the bronchial orifice and pulmonary
      artery, double-sleeve resection is an alternative to pneumonectomy. We have
      performed robotic double-sleeve resection in 4 patients and describe herein the
      technical aspects. No patient was converted to thoracotomy and no postoperative
      complication occurred. All the patients were alive during follow-up. Robotic
      double-sleeve resection is feasible in selected cases.

PMID- 29579168
TI  - Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation.
AB  - Aims: It is recommended to perform atrial fibrillation ablation with continuous
      anticoagulation. Continuous apixaban has not been tested. Methods and results: We
      compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA,
      international normalized ratio 2-3) in atrial fibrillation patients at risk of
      stroke a prospective, open, multi-centre study with blinded outcome assessment.
      Primary outcome was a composite of death, stroke, or bleeding (Bleeding Academic
      Research Consortium 2-5). A high-resolution brain magnetic resonance imaging
      (MRI) sub-study quantified acute brain lesions. Cognitive function was assessed
      by Montreal Cognitive Assessment (MoCA) at baseline and at end of follow-up.
      Overall, 674 patients (median age 64 years, 33% female, 42% non-paroxysmal atrial
      fibrillation, 49 sites) were randomized; 633 received study drug and underwent
      ablation; 335 undertook MRI (25 sites, 323 analysable scans). The primary outcome
      was observed in 22/318 patients randomized to apixaban, and in 23/315 randomized
      to VKA {difference -0.38% [90% confidence interval (CI) -4.0%, 3.3%], non
      inferiority P = 0.0002 at the pre-specified absolute margin of 0.075}, including
      2 (0.3%) deaths, 2 (0.3%) strokes, and 24 (3.8%) ISTH major bleeds. Acute small
      brain lesions were found in a similar number of patients in each arm [apixaban
      44/162 (27.2%); VKA 40/161 (24.8%); P = 0.64]. Cognitive function increased at
      the end of follow-up (median 1 MoCA unit; P = 0.005) without differences between
      study groups. Conclusions: Continuous apixaban is safe and effective in patients
      undergoing atrial fibrillation ablation at risk of stroke with respect to
      bleeding, stroke, and cognitive function. Further research is needed to reduce
      ablation-related acute brain lesions.

PMID- 29579171
TI  - A comparison of early redo surgery rates in Mosaic porcine and Perimount bovine
      pericardial valves.
AB  - OBJECTIVES: The objective of this study was to compare rates of redo surgery for
      the Medtronic Mosaic 305 A Porcine Prosthesis and the Carpentier-Edwards
      Perimount Pericardial Aortic Bioprosthesis 2900. METHODS: This was a single
      centre retrospective observational study. We included all 1018 patients who
      underwent aortic valve replacement with a Mosaic (n = 216) or Perimount (n = 809)
      bioprosthesis between October 2000 and August 2008. The total follow-up was 1508
      patient-years for the Mosaic valve and 5813 for the Perimount valve. The maximal
      follow-up and interquartile range were 14.8 and 7.0 years for the Mosaic valve
      and 15.1 and 5.6 years for the Perimount valve, respectively. A propensity score
      weighted version of the Cox model, Kaplan-Meier analysis and multivariate
      regression model was used. RESULTS: Despite no statistical difference in the
      number of non-structural valve deterioration cases between valves, redo surgery
      occurred earlier in 10 (4.6%) Mosaic than for 17 (2.1%) Perimount valves (P =
      0.02) and was required for structural valve deterioration in 5 (2.3%) Mosaic
      valves when compared with 7 (0.9%; P = 0.04) Perimount valves. Four of 5 Mosaic
      failures occurred before 5 years, whereas all Perimount failures occurred after 5
      years. Redo surgery for non-structural valve deterioration occurred in 3 patients
      with Mosaic valves (1.4%) and no patients with Perimount valves. Surgery for the
      remaining patients with Perimount valves was due to infection or aortic disease.
      CONCLUSIONS: Early redo surgery for structural valve degeneration was uncommon
      but occurred earlier for the Mosaic porcine than the Perimount bovine pericardial
      replacement aortic valve.

PMID- 29579170
TI  - miR-122 Regulates LHR Expression in Rat Granulosa Cells by Targeting Insig1 mRNA.
AB  - Luteinizing hormone/chorionic gonadotropin receptor (LHR) expression in the ovary
      is regulated by a messenger RNA (mRNA) binding protein, which specifically binds
      to the coding region of LHR mRNA. We have shown that miR-122, a short noncoding
      RNA, mediates LHR mRNA levels by modulating the expression of LHR mRNA-binding
      protein (LRBP) through the regulation of sterol regulatory element binding
      protein (SREBP) activation. The present results show that miR-122 regulates LRBP
      levels by increasing the processing of SREBP through the degradation of Insig1,
      the anchoring protein of SREBP. We present evidence showing that mRNA and protein
      levels of Insig1 undergo a time-dependent increase following the treatment of rat
      granulosa cells with follicle-stimulating hormone (FSH), which leads to a
      decrease in LRBP levels. Furthermore, overexpression of miR-122 using an
      adenoviral vector (AdmiR-122) abolished FSH-induced increases in Insig1 mRNA and
      protein. We further confirmed the role of Insig1 by showing that inhibition of
      Insig1 using a specific small interfering RNA prior to FSH treatment resulted in
      the abrogation of LHR upregulation. Silencing of Insig1 also reversed FSH
      mediated decreases in SREBP and LRBP activation. These results show that
      decreased levels of miR-122 increase Insig1 and suppress SREBP processing in
      response to FSH stimulation of rat granulosa cells.

PMID- 29579172
TI  - MicroRNAs in the Mammalian Gut Endocrine Lineage.
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules that modulate gene
      expression at the posttranscriptional level. Numerous reports have elucidated the
      importance of miRNAs in the regulation of a wide array of biological processes
      including metabolism and energy homeostasis. miRNAs in the endocrine pancreas
      have been intensively studied over the last 15 years and linked to pancreatic
      islet development and function. In comparison, knowledge of miRNAs in gut
      endocrine cells, or enteroendocrine cells (EECs), is severely lacking. EECs have
      important roles in systemic energy homeostasis, are highly relevant to type 2
      diabetes etiology, and may be critical to the mechanisms that underlie the rapid
      positive metabolic effects of bariatric surgery. Very recent studies reveal that
      several miRNAs are highly enriched in mature EECs and/or in intestinal stem cells
      that are primed to the EEC lineage. Moreover, functional experiments in
      enteroids/intestinal organoids suggest that some of these miRNAs may be important
      for the regulation of EEC differentiation and function. Another report has raised
      the possibility that EECs secrete miRNAs into circulation. These intriguing
      findings merit further investigation, particularly as it pertains to EEC miRNAs
      as novel therapeutic targets in type 2 diabetes and related diseases.

PMID- 29579173
TI  - Values We Share in Publishing Endocrinology: People and Process.

PMID- 29579174
TI  - Non-herbal tea consumption and ovarian cancer risk: a systematic review and meta
      analysis of observational epidemiologic studies with indirect comparison and dose
      response analysis.
AB  - Ovarian cancer (OC) accounts for 4% of female malignancies worldwide, and its
      prognosis is unfavorable. Currently available epidemiologic data suggest that non
      herbal tea consumption may reduce OC risk, but these evidences are inconsistent.
      A comprehensive literature search for observational epidemiologic studies
      reporting associations between non-herbal tea consumption and OC risk was
      conducted in electronic databases. A random-effects model was used to synthesize
      effect measures in binary meta-analysis, and adjusted indirect comparison was
      used to compare whether there was a difference in effects between green tea (GT)
      and black tea (BT). Both linear and non-linear models were used to explore the
      dose-response relationship. Fourteen studies were included, and we obtained an
      inverse and significant pooled estimate in binary meta-analysis [risk ratio
      (RR)pool = 0.76, 95% confidence interval (CI) 0.61-0.95, PCochran < 0.001, I2 =
      81.5%]. No publication bias was identified in binary meta-analysis. In binary
      meta-analysis stratified by tea types, we observed a significant association for
      GT (RRpool = 0.64, 95% CI 0.45-0.90, PCochran = 0.071, I2 = 53.6%), but not BT
      (RRpool = 0.85, 95% CI 0.65-1.12, PCochran = 0.007, I2 = 65.9%). Indirect
      comparison, which treated BT as the reference, showed an inverse but non
      significant association (RRGT versus BT = 0.74, 95% CI 0.48-1.15). Both linear
      and non-linear models found that OC risk decreased as the consumption levels of
      total non-herbal tea increased. However, the dose-response relationship was
      stronger for GT when compared with BT. Our results suggest that non-herbal tea,
      especially GT, is associated with a reduced risk of OC. Future studies should
      explore biochemical evidence regarding the variation in chemopreventive effects
      between different types of non-herbal tea.

PMID- 29579175
TI  - The Cell Type-Specific Expression of Lhcgr in Mouse Ovarian Cells: Evidence for a
      DNA-Demethylation-Dependent Mechanism.
AB  - The luteinizing hormone receptor (LHCGR) is expressed at low levels in mural
      granulosa cells and cumulus cells of antral follicles and is induced dramatically
      in granulosa cells but not in cumulus cells by follicle-stimulating hormone
      (FSH). Therefore, we hypothesized that FSH not only activates transcription
      factors controlling Lhcgr expression but also alters other events to permit and
      enhance Lhcgr expression in granulosa cells but not in cumulus cells. In
      granulosa cells, the level of DNA methylation in the Lhcgr promoter region was
      significantly decreased by equine chorionic gonadotropin (eCG) in vivo. However,
      in cumulus cells, hypermethylation of the Lhcgr promoter remained after eCG
      stimulation. eCG induced estrogen production from testosterone (T) and retinoic
      acid (RA) synthesis in granulosa cells. When either T or RA in the presence or
      absence of FSH was added to granulosa cell cultures, the combined treatment with
      FSH and RA induced demethylation of Lhcgr-promoter region and Lhcgr expression.
      FSH-dependent RA synthesis was negatively regulated by coculture of granulosa
      cells with denuded oocytes, suggesting that oocyte-secreted factors downregulate
      RA production in cumulus cells where Lhcgr expression was not induced.
      Strikingly, treatment of cultured cumulus-oocyte complexes with a SMAD inhibitor,
      SB431542, significantly induced RA production, demethylation of Lhcgr-promoter
      region, and Lhcgr expression in cumulus cells. These results indicate the
      demethylation of the Lhcgr-promoter region is mediated, at least in part, by RA
      synthesis and is a key mechanism regulating the cell type-specific
      differentiation during follicular development.

PMID- 29579176
TI  - Cognitive Function, Consent for Participation, and Compliance With Wearable
      Device Protocols in Older Adults.
AB  - Background: Population-based studies of older adults increasingly use wearable
      devices to measure activity and sleep. Whether cognitive impairment reduces
      consent and compliance has not been assessed. Methods : In the context of a
      nationally representative cohort of community-dwelling adults aged 62-90,
      individuals were invited to participate in a sleep and activity substudy that
      required wearing a wrist actigraph for 72 consecutive hours. Cognitive function
      in the parent study was assessed with the survey adaptation of the Montreal
      Cognitive Assessment, and individuals were categorized as normal, mild cognitive
      impairment, or dementia. Participants were asked to press an event marker on the
      actigraph when they started trying to fall asleep and when they awoke each day.
      Logistic and negative binomial regressions were used to link cognitive status to
      nonconsent, returning usable data, wearing the actigraph three full days, ever
      taking the device off-wrist during the 3-day study period, and pushing the event
      markers, controlling for demographics. Results: Cognitive status was not
      associated with nonconsent, returning usable data, off-wrist, or missing days.
      However, individuals classified with dementia were more likely to miss bedtime
      and wake-up event markers. Individuals classified as mild cognitive impairment
      were more likely to miss wake-up event markers. Conclusions: Impaired cognition
      does not seem to be a barrier to compliance with simply wearing a device but may
      affect compliance with additional action such as pressing event markers.

PMID- 29579178
TI  - Rupture of a stenotic thin-cap fibroatheroma in an area of low endothelial shear
      stress: Implication for mechanism of acute coronary syndromes.

PMID- 29579177
TI  - Fshb Knockout Mouse Model, Two Decades Later and Into the Future.
AB  - In 1997, nearly 20 years ago, we reported the phenotypes of follicle-stimulating
      hormone (FSH) beta (Fshb) null mice. Since then, these mice have been useful for
      various physiological and genetic studies in reproductive and skeletal biology.
      In a 2009 review titled "FSHbeta Knockout Mouse Model: A Decade Ago and Into the
      Future," I summarized the need for and what led to the development of an FSH
      deficient mouse model and its applications, including delineation of the emerging
      extragonadal roles of FSH in bone cells by using this genetic model. These
      studies opened up exciting avenues of research on osteoporosis and now extend
      into those on adiposity in postmenopausal women. Here, I summarize the progress
      made with this mouse model since 2009 with regard to FSH rerouting in vivo,
      deciphering the role of N-glycosylation on FSHbeta, roles of FSH in somatic-germ
      cell interactions in gonads, and provide a road map that is anticipated to emerge
      in the near future. Undoubtedly, the next 10 years should be an even more
      exciting time to explore the fertile area of FSH biology and its implications for
      basic and clinical reproductive physiology research.

PMID- 29579180
TI  - Expanding the global borders of heart failure: the SHOP and PEOPLE studies.

PMID- 29579179
TI  - A Bayesian framework for multiple trait colocalization from summary association
      statistics.
AB  - Motivation: Most genetic variants implicated in complex diseases by genome-wide
      association studies (GWAS) are non-coding, making it challenging to understand
      the causative genes involved in disease. Integrating external information such as
      quantitative trait locus (QTL) mapping of molecular traits (e.g. expression,
      methylation) is a powerful approach to identify the subset of GWAS signals
      explained by regulatory effects. In particular, expression QTLs (eQTLs) help
      pinpoint the responsible gene among the GWAS regions that harbor many genes,
      while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that
      impact gene expression which in turn affect disease risk. In this work, we
      propose multiple-trait-coloc (moloc), a Bayesian statistical framework that
      integrates GWAS summary data with multiple molecular QTL data to identify
      regulatory effects at GWAS risk loci. Results: We applied moloc to schizophrenia
      (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52
      candidate genes that influence SCZ through methylation. Our method can be applied
      to any GWAS and relevant functional data to help prioritize disease associated
      genes. Availability and implementation: moloc is available for download as an R
      package (https://github.com/clagiamba/moloc). We also developed a web site to
      visualize the biological findings (icahn.mssm.edu/moloc). The browser allows
      searches by gene, methylation probe and scenario of interest. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29579181
TI  - Earthworm-induced shifts in microbial diversity in soils with rare versus
      established invasive earthworm populations.
AB  - European earthworms have colonised many parts of Australia, although their impact
      on soil microbial communities remains largely uncharacterised. An experiment was
      conducted to contrast the responses to Aporrectodea trapezoides introduction
      between soils from sites with established (Talmo, 64 A. trapezoides m-2) and rare
      (Glenrock, 0.6 A. trapezoides m-2) A. trapezoides populations. Our hypothesis was
      that earthworm introduction would lead to similar changes in bacterial
      communities in both soils. The effects of earthworm introduction (earthworm
      activity and cadaver decomposition) did not lead to a convergence of bacterial
      community composition between the two soils. However, in both soils, the
      Firmicutes decreased in abundance and a common set of bacteria responded
      positively to earthworms. The increase in the abundance of Flavobacterium,
      Chitinophagaceae, Rhodocyclaceae and Sphingobacteriales were consistent with
      previous studies. Evidence for possible soil resistance to earthworms was
      observed, with lower earthworm survival in Glenrock microcosms coinciding with A.
      trapezoides rarity in this site, lower soil organic matter and clay content and
      differences in the diversity and abundance of potential earthworm mutualist
      bacteria. These results suggest that while the impacts of earthworms vary between
      different soils, the consistent response of some bacteria may aid in predicting
      the impacts of earthworms on soil ecosystems.

PMID- 29579182
TI  - eDNA from roots: a robust tool for determining Phytophthora communities in
      natural ecosystems.
AB  - Proper isolation and identification of Phytophthora species is critical due to
      their broad distribution and huge impact on natural ecosystems throughout the
      world. In this study, five different sites were sampled and seven methods were
      compared to determine the Phytophthora community. Three traditional isolation
      methods were conducted (i) soil baiting, (ii) filtering of the bait water and
      (iii) isolation from field roots using Granny Smith apples. These were compared
      to four sources of eDNA used for metabarcoding using Phytophthora-specific
      primers on (i) sieved field soil, (ii) roots from field, (iii) filtered baiting
      water and (iv) roots from bait plants grown in the glasshouse in soil collected
      from these sites. Six Phytophthora species each were recovered by soil baiting
      using bait leaves and from the filtered bait water. No Phytophthora species were
      recovered from Granny Smith apples. eDNA extracted from field roots detected the
      highest number of Phytophthora species (25). These were followed by direct DNA
      isolation from filters (24), isolation from roots from bait plants grown in the
      glasshouse (19), and DNA extraction from field soil (13). Therefore, roots were
      determined to be the best substrate for detecting Phytophthora communities using
      eDNA.

PMID- 29579183
TI  - Effects of bottom-water hypoxia on sediment bacterial community composition in a
      seasonally hypoxic enclosed bay (Omura Bay, West Kyushu, Japan).
AB  - The bacterial community strongly drives carbon and other biogeochemical cycles in
      marine sediment. However, little is known about the impact of dissolved oxygen
      (DO) availability on bacterial community composition. To fill this gap, we
      examined diversity, richness and structure of the bacterial population for three
      consecutive years (2011-2013) in the uppermost (0-5 and 0-7 mm depth) and the
      subsurface layers (5-10 and 7-14 mm depth) of Omura Bay, Kyushu, Japan, a
      seasonally hypoxic enclosed bay. Automated ribosomal intergenic spacer analysis
      revealed a unimodal pattern of diversity indices with DO, peaking at the suboxic
      (11 MUM O2) condition. Shifts in the bacterial communities were also evident in
      response to the availability of DO. Changes in the operational taxonomic units
      (OTUs) that were less abundant accounted for a large part of the community
      dissimilarity. It was further demonstrated that the relative abundance of OTUs
      affiliated with Gammaproteobacteria was correlated positively with DO, while that
      with Deltaproteobacteria was inversely correlated with DO. These results strongly
      suggest that DO availability of bottom water plays a fundamental role in shaping
      the bacterial community in sediment surfaces of shallow coastal areas.

PMID- 29579184
TI  - Arteritis of Takayasu in Western man of 31 years.

PMID- 29579187
TI  - Operator volume and mortality in percutaneous coronary intervention: a call for
      better competency metrics.

PMID- 29579185
TI  - Safety of lymphadenectomy during video-assisted thoracic surgery lobectomy:
      analysis from a national database.
AB  - OBJECTIVES: The Italian VATS Group database was accessed to evaluate whether
      preoperative and intraoperative factors may affect the safety of lymphadenectomy
      (LA) during video-assisted thoracic surgery lobectomy. METHODS: All video
      assisted thoracic surgery lobectomy procedures performed between 1 January 2014
      and 30 March 2017 for non-small-cell lung cancer with cN0 or cN1 disease were
      identified in the database. LA safety was evaluated based on intraoperative
      (operative time, bleeding and conversion rate) and postoperative (30-day
      morbidity and mortality, chest drain duration and length of stay) outcomes and
      was correlated with the number of resected lymph nodes and the rates of nodal
      upstaging. Continuous variables were presented as mean +/- standard deviation and
      compared using the unpaired t-test; the chi2 test was used for categorical
      variables. Univariable analysis was performed on selected variables. Significant
      variables (P < 0.30) were entered into a Cox multivariable logistic regression
      model, using the overall and specific occurrence of complications as dependent
      variables. The Spearman's rank correlation coefficient was applied as needed.
      RESULTS: A total of 3181 cases (2077 men, 65.3%; mean age of 69 years) met the
      enrolment criteria. Final pathology was consistent with adenocarcinoma (n = 2262,
      67.5%), squamous cell (n = 520, 15.5%), typical (n = 184, 5.5%) and atypical
      carcinoid (n = 48, 1.4%) and other (n = 335, 10%). The mean number of resected
      lymph nodes was 13.42 +/- 8.24; nodal upstaging occurred in 308 of 3181 (9.68%)
      cases. Six hundred and fifty-five complications were recorded in 404 (12.7%)
      patients; in this series, no mortality was observed. Univariable and
      multivariable analyses did not show any association between the extension of LA
      and intraoperative or postoperative outcomes. The number of resected lymph nodes
      and nodal upstagings showed a minimal correlation with intraoperative outcomes
      and a moderate correlation with postoperative air leak (rho = 0.35 and rho =
      0.48, respectively), arrhythmia (rho = 0.29 and rho = 0.35, respectively), chest
      drain duration (rho = 0.35 and rho = 0.51, respectively) and length of stay (rho
      = 0.35). CONCLUSIONS: Based on the VATS Group data, video-assisted thoracic
      surgery LA proved to be safe and displayed good outcomes even when performed with
      an extended approach.

PMID- 29579186
TI  - Arrhythmias in congenital heart disease: a position paper of the European Heart
      Rhythm Association (EHRA), Association for European Paediatric and Congenital
      Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on
      Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.
AB  - The population of patients with congenital heart disease (CHD) is continuously
      increasing with more and more patients reaching adulthood. A significant portion
      of these young adults will suffer from arrhythmias due to the underlying
      congenital heart defect itself or as a sequela of interventional or surgical
      treatment. The medical community will encounter an increasing challenge as even
      most of the individuals with complex congenital heart defects nowadays become
      young adults. Within the past 20 years, management of patients with arrhythmias
      has gained remarkable progress including pharmacological treatment, catheter
      ablation, and device therapy. Catheter ablation in patients with CHD has
      paralleled the advances of this technology in pediatric and adult patients with
      structurally normal hearts. Growing experience and introduction of new techniques
      like the 3D mapping systems into clinical practice have been particularly
      beneficial for this growing population of patients with abnormal cardiac anatomy
      and physiology. Finally, device therapies allowing maintanence of chronotropic
      competence and AV conduction, improving haemodynamics by cardiac
      resynchronization, and preventing sudden death are increasingly used. For
      pharmacological therapy, ablation procedures, and device therapy decision making
      requires a deep understanding of the individual pathological anatomy and
      physiology as well as detailed knowledge on natural history and long-term
      prognosis of our patients. Composing expert opinions from cardiology and
      paediatric cardiology as well as from non-invasive and invasive electrophysiology
      this position paper was designed to state the art in management of young
      individuals with congenital heart defects and arrhythmias.

PMID- 29579188
TI  - Yellow traffic lights and grey zone fractional flow reserve values: stop or go?

PMID- 29579189
TI  - Cardiac voltage-gated sodium channel mutations associated with left atrial
      dysfunction and stroke in children.
AB  - Aims: Cardiac atrial arrhythmias are the most common type of heart rhythm
      disorders. Its genetic elucidation remains challenging with poor understanding of
      cellular and molecular processes. These arrhythmias usually affect elderly
      population but in rare cases, young children may also suffer from such electrical
      diseases. Severe complications, including stroke, are commonly age related. This
      study aims to identify a genetic link between electro-mechanic atrial dysfunction
      and stroke in children. Methods and results: In two unrelated boys of 11 and 14
      years with both stroke and atrial arrhythmias, the clinical phenotype was
      determined through a complete physical examination, electrocardiogram (ECG),
      Holter ECG, and computed tomography. The genetic testing was performed on a large
      95 genes panel implicated in myocardial electrical imbalance, using the next
      generation sequencing method. The panel also includes the genes usually
      associated with the development of cardiomyopathies. In one child, a left atrial
      dilation was observed. The 2nd boy suffered from atrial standstill. Both suffered
      from atrial bradycardia, flutter, and fibrillation. The complete genetic testing
      revealed the SCN5A c.3823G>A (p.D1275N) mutation in the first family, c.1141-2A>G
      and c.3157G>A (p.E1053K) mutations in the second family. Conclusion: Our results
      strengthen the association between Nav1.5 mutations and the occurrence of stroke
      in young patients. It emphasizes the need to look for atrial myopathy in the
      decision process for anticoagulation in young patients with atrial arrhythmic
      events.

PMID- 29579190
TI  - 27-Hydroxycholesterol Is an Estrogen Receptor beta-Selective Negative Allosteric
      Modifier of 17beta-Estradiol Binding.
AB  - Estrogens bind to two nuclear estrogen receptor (ER) subtypes, ERalpha and
      ERbeta, which are expressed in differing amounts in various tissues. The
      endogenous estrogen, 17beta-estradiol (E2), binds to both subtypes with nearly
      equal affinity and is the prototypical agonist. Selective estrogen receptor
      modulators (SERMs) may bind to both subtypes with equivalent affinities but have
      agonist activities in some tissues while having antagonist activities in others.
      In the present study, we demonstrate that the first reported endogenous SERM, 27
      hydroxycholesterol (27-OHC), binds preferentially (>100-fold) to ERbeta over
      ERalpha. Furthermore, 27-OHC is not able to fully compete with E2 binding,
      suggesting the two may bind at different sites. We provide an allosteric ternary
      complex model for the simultaneous binding of 27-OHC and E2 to ERbeta, which
      accurately describes the binding data we have observed. We conclude that 27-OHC
      is a negative allosteric modifier of E2 binding, with an inhibitor constantof 50
      nM and cooperativity factor (alpha) of 0.036. We also propose an in silico three
      dimensional model of the simultaneous binding to guide future experiments.
      Further study of this unique binding model may allow for the discovery of novel
      ERbeta-selective ligands and potentially explain the lack of effectiveness of
      ERbeta-selective agonists in humans vs preclinical models.

PMID- 29579192
TI  - New prospects for PCSK9 inhibition?

PMID- 29579191
TI  - Glycosyltransferase genes that cause monogenic congenital disorders of
      glycosylation are distinct from glycosyltransferase genes associated with complex
      diseases.
AB  - Glycosylation of proteins, lipids and proteoglycans in human cells involves at
      least 167 identified glycosyltransferases (GTfs), and these orchestrate the
      biosynthesis of diverse types of glycoconjugates and glycan structures. Mutations
      in this part of the genome-the GTf-genome-cause more than 58 rare, monogenic
      congenital disorders of glycosylation (CDGs). They are also statistically
      associated with a large number of complex phenotypes, diseases or predispositions
      to complex diseases based on Genome-Wide Association Studies (GWAS). CDGs are
      extremely rare and often with severe medical consequences. In contrast, GWAS are
      likely to identify more common genetic variations and generally involve less
      severe and distinct traits. We recently confirmed that structural defects in GTf
      genes are extremely rare, which seemed at odds with the large number of GWAS
      pointing to GTf-genes. To resolve this issue, we surveyed the GTf-genome for
      reported CDGs and GWAS candidates; we found little overlap between the two groups
      of genes. Moreover, GTf-genes implicated by CDG or GWAS appear to constitute
      different classes with respect to their: (i) predicted roles in glycosylation
      pathways; (ii) potential for partial redundancy by closely homologous genes; and
      (iii) transcriptional regulation as evaluated by RNAseq data. Our analysis
      suggest that more complex traits are caused by dysregulation rather than
      structural deficiency of GTfs, which suggests that some glycosylation reactions
      may be predicted to be under tight regulation for fine-tuning of important
      biological functions.

PMID- 29579193
TI  - Divide and conquer: improving parental understanding of health-related
      instructions using sequential pictorial instructions.
AB  - Patient misunderstandings of healthcare-related instructions result in
      significant health, social and economic consequences. Pushing the boundaries of
      traditional academic methods may offer strategies that promote new ways to
      improve communication and understanding between healthcare providers, caregivers
      and patients. Comics can be an educational tool, offering an innovative strategy
      to communicate health-related information. Our study objective was to compare
      parents' understanding of health-related instructions (i.e. prescription labels,
      medical instructions and emergency situation scenarios) that were presented using
      two different formats-sequential pictorial instructions (SPIs) versus written
      text instructions (WRIs).This was a cross-sectional study to compare parents'
      understanding of health-related instructions for pediatric patients using
      structured SPIs versus WRIs. Parents (n = 359, 18-82 years old) of pediatric
      patients were given a card with instructions that were presented as SPIs (n =
      195, 54.3%) or WRIs (n = 164, 45.7%), and then they completed a questionnaire.
      Total (14 questions) and grouped scores (10 questions) for parental comprehension
      of prescription and medical emergency instructions were significantly higher
      among participants viewing the SPIs than those viewing the WRIs in both English
      and Spanish. The mean understanding of instructions significantly increased from
      6% to 12.2% when comparing the WRI versus the SPI.Our initial findings indicate
      that parents and caregivers of pediatric patients had significantly better
      understanding and recall of instructions delivered using SPIs than using WRIs.

PMID- 29579194
TI  - Using social norms theory for health promotion in low-income countries.
AB  - Social norms can greatly influence people's health-related choices and
      behaviours. In the last few years, scholars and practitioners working in low- and
      mid-income countries (LMIC) have increasingly been trying to harness the
      influence of social norms to improve people's health globally. However, the
      literature informing social norm interventions in LMIC lacks a framework to
      understand how norms interact with other factors that sustain harmful practices
      and behaviours. This gap has led to short-sighted interventions that target
      social norms exclusively without a wider awareness of how other institutional,
      material, individual and social factors affect the harmful practice. Emphasizing
      norms to the exclusion of other factors might ultimately discredit norms-based
      strategies, not because they are flawed but because they alone are not sufficient
      to shift behaviour. In this paper, we share a framework (already adopted by some
      practitioners) that locates norm-based strategies within the wider array of
      factors that must be considered when designing prevention programmes in LMIC.

PMID- 29579196
TI  - Safety and efficacy of delivering high-power short-duration radiofrequency
      ablation lesions utilizing a novel temperature sensing technology.
AB  - Aims: Delivery of high-power short-duration radiofrequency (RF) ablation lesions
      is not commonly used, in part because conventional thermocouple (TC) technology
      underestimates tissue temperature, increasing the risk of steam pop, and thrombus
      formation. We aimed to test whether utilization of an ablation catheter equipped
      with a highly accurate novel TC technology could facilitate safe and effective
      delivery of high-power RF lesions. Methods and results: Adult male Yorkshire
      swine were used for the study. High-power short-duration ablations (10-s total;
      90 W for 4 s followed by 50 W for 6 s) were delivered using an irrigated force
      sensing catheter, equipped with six miniature TC sensors embedded in the tip
      electrode shell. Power modulation was automatically performed when the
      temperature reached 65 degrees C. Ablation parameters were recorded and
      histopathological analysis was performed to assess lesion formation. One hundred
      and fourteen RF applications, delivered using the study ablation protocol in the
      ventricles of eight swine [53 in the right ventricle (RV), 61 in the left
      ventricle (LV)], were analysed. Average power delivered was 55.4 +/- 5.3 W and
      none of the ablations resulted in a steam pop. Fourteen out of the 114 (12.3%)
      lesions were transmural. The mean lesion depth was 3.9 +/- 1.1 mm for the 100 non
      transmural lesions. Similar ablation parameters resulted in bigger impedance drop
      (11.6 Omega vs. 9.1 Omega, P = 0.009) and deeper lesions in the LV compared with
      the RV (4.3 +/- 1.2 mm vs. 3.3 +/- 0.8 mm, P < 0.001). Conclusion: Delivery of
      high-power short-duration RF energy applications, facilitated by a novel ablation
      catheter system equipped with advanced TC technology, is feasible, safe, and
      results in the formation of effective ablation lesions.

PMID- 29579195
TI  - Negligible Impact of Mass Screening and Treatment on Mesoendemic Malaria
      Transmission at West Timor in Eastern Indonesia: A Cluster-Randomized Trial.
AB  - Background: Mass screening and treatment (MST) aims to reduce malaria risk in
      communities by identifying and treating infected persons without regard to
      illness. Methods: A cluster-randomized trial evaluated malaria incidence with and
      without MST. Clusters were randomized to 3, 2, or no MST interventions: MST3, 6
      clusters (156 households/670 individuals); MST2, 5 clusters (89 households/423
      individuals); and MST0, 5 clusters (174 households/777 individuals). All clusters
      completed the study with 14 residents withdrawing. In a cohort of 324
      schoolchildren (MST3, n = 124; MST2, n = 57; MST0, n = 143) negative by
      microscopy at enrollment, we evaluated the incidence density of malaria during 3
      months of MST and 3 months following. The MST intervention involved community
      wide expert malaria microscopic screening and standard therapy with
      dihydroartemisinin-piperaquine and primaquine for glucose-6 phosphate
      dehydrogenase-normal subjects. All blood examinations included polymerase chain
      reaction assays, which did not guide on-site treatment. Results: The risk ratios
      for incidence density of microscopically patent malaria in MST3 or MST2 relative
      to that in MST0 clusters were 1.00 (95% confidence interval [CI], .53-1.91) and
      1.22 (95% CI, .42-3.55), respectively. Similar results were obtained with
      molecular analysis and species-specific (P. falciparum and P. vivax) infections.
      Microscopically subpatent, untreated infections accounted for 72% of those
      infected. Conclusions: Two or 3 rounds of MST within 3 months did not impact the
      force of anopheline mosquito-borne infection in these communities. The high rate
      of untreated microscopically subpatent infections likely explains the observed
      poor impact. Clinical Trials Registration: NCT01878357.

PMID- 29579197
TI  - Staged surgery for an unusual combination of cardiac and tracheal anomalies.
AB  - Herein, the case of an infant initially diagnosed with left pulmonary artery
      sling, ventricular septal defect and a small atrial septal defect is described.
      Further diagnostic work-up revealed tracheobronchial anomalies and the presence
      of an anomalous origin of the left coronary artery from the pulmonary artery. The
      staged surgical management is described.

PMID- 29579199
TI  - Direct detection of carbapenem resistance determinants in clinical specimens
      using immunochromatographic lateral flow devices.

PMID- 29579198
TI  - A comprehensive evaluation of alignment software for reduced representation
      bisulfite sequencing data.
AB  - Motivation: The rapid development of next-generation sequencing technology
      provides an opportunity to study genome-wide DNA methylation at single-base
      resolution. However, depletion of unmethylated cytosines brings challenges for
      aligning bisulfite-converted sequencing reads to a large reference. Software
      tools for aligning methylation reads have not yet been comprehensively evaluated,
      especially for the widely used reduced representation bisulfite sequencing (RRBS)
      that involves enrichment for CpG islands (CGIs). Results: We specially developed
      a simulator, RRBSsim, for benchmarking analysis of RRBS data. We performed
      extensive comparison of seven mapping algorithms for methylation analysis in both
      real and simulated RRBS data. Eighteen lung tumors and matched adjacent tissues
      were sequenced by the RRBS protocols. Our empirical evaluation found that
      methylation results were less consistent between software tools for CpG sites
      with low sequencing depth, medium methylation level, on CGI shores or gene body.
      These observations were further confirmed by simulations that indicated software
      tools generally had lower recall of detecting these vulnerable CpG sites and
      lower precision of estimating methylation levels in these CpG sites. Among the
      software tools tested, bwa-meth and BS-Seeker2 (bowtie2) are currently our
      preferred aligners for RRBS data in terms of recall, precision and speed.
      Existing aligners cannot efficiently handle moderately methylated CpG sites and
      those CpG sites on CGI shores or gene body. Interpretation of methylation results
      from these vulnerable CpG sites should be treated with caution. Our study reveals
      several important features inherent in methylation data, and RRBSsim provides
      guidance to advance sequence-based methylation data analysis and methodological
      development. Availability and implementation: RRBSsim is a simulator for
      benchmarking analysis of RRBS data and its source code is available at
      https://github.com/xwBio/RRBSsim or https://github.com/xwBio/Docker-RRBSsim.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29579200
TI  - Mechanical dyssynchrony of the left atrium during sinus rhythm is associated with
      history of stroke in patients with atrial fibrillation.
AB  - Aims: We sought to evaluate the relationship between left atrial (LA) mechanical
      dyssynchrony and history of stroke or transient ischaemic attack (TIA) in
      patients with atrial fibrillation (AF). We hypothesized that mechanical
      dyssynchrony of the LA is associated with history of stroke/TIA independent of LA
      function and Cardiac failure, Hypertension, Age, Diabetes, Stroke/transient
      ischaemic attack (TIA), VAscular disease, and Sex category (CHA2DS2-VASc) score
      in patients with AF. Methods and results: We conducted a cross-sectional study of
      246 patients with a history of AF (59 +/- 10 years, 29% female, 26% non
      paroxysmal AF) referred for catheter ablation to treat drug-refractory AF who
      underwent preablation cardiac magnetic resonance (CMR) in sinus rhythm. Using
      tissue-tracking CMR, we measured the LA longitudinal strain and strain rate in
      each of 12 equal-length segments in two- and four-chamber views. We defined
      indices of LA mechanical dyssynchrony, including the standard deviation of the
      time to the peak longitudinal strain (SD-TPS). Patients with a prior history of
      stroke or TIA (n = 23) had significantly higher SD-TPS than those without (n =
      223) (39.9 vs. 23.4 ms, P < 0.001). Multivariable analysis showed that SD-TPS was
      associated with stroke/TIA after adjusting for the CHA2DS2-VASc score, LA minimum
      index volume, and the peak LA longitudinal strain (P < 0.001). The receiver
      operating characteristics curve showed that SD-TPS identified patients with
      stroke/TIA more accurately than CHA2DS2-VASc score alone (c-statistics: 0.82 vs.
      0.75, P < 0.001). Conclusion: Higher mechanical dyssynchrony of the LA during
      sinus rhythm is associated with a history of stroke/TIA in patients with AF.

PMID- 29579201
TI  - Intramacrophage Mycobacterium tuberculosis efflux pump gene regulation after
      rifampicin and verapamil exposure.
AB  - Objectives: Since resistance of Mycobacterium tuberculosis (Mtb) partially
      derives from efflux pumps (EPs) in the plasma membrane, the current study
      evaluates EPs in Mtb exposed to rifampicin in the presence of the EP inhibitor
      verapamil, within a macrophage environment. Methods: Human acute monocytic
      leukaemia cell line THP-1 was infected with Mtb H37Rv and exposed to rifampicin
      and verapamil alone and in combination for 24 and 72 h. After RNA extraction,
      quantitative PCR was carried out for 11 EP genes using SYBR green PCR master mix
      in the StepOneTM Real-Time PCR System. Results: After 24 h of exposure to
      rifampicin, Mtb H37Rv showed that 10 EP genes were up-regulated when compared
      with the control. The rifampicin/verapamil combination induced down-regulation of
      54.5% (6/11) of the EP genes. At 72 h, rifampicin exposure induced up-regulation
      of 10 EP genes and rifampicin/verapamil induced down-regulation of 8 EP genes,
      which suggests effective EP-inhibitory activity of verapamil against Mtb H37Rv in
      an intramacrophage environment. Conclusions: The current study demonstrated that
      rifampicin/verapamil caused down-regulation of several EP genes in Mtb inside the
      macrophage environment. In vivo trials may show that rifampicin/verapamil therapy
      could be of value in enhancing anti-TB treatment.

PMID- 29579203
TI  - Reorienting Norwegian mental healthcare services: listen to patients' learning
      appetite.
AB  - Reorientation of healthcare services towards more efficient health promotion
      interventions is an urgent matter. Despite policies and guidelines being in
      place, it is the least developed key action area of the Ottawa charter. User
      involvement, or the voice of the patient, is missing from the knowledge base of
      health promotion in the mental healthcare services. The aim of this study was to
      add experiential knowledge from former patients. We explored the lived experience
      of 12 former inpatients at a mental healthcare hospital. We describe what they
      perceive as mental health promoting efforts. A salutogenic theoretical framework
      and the methodology of interpretative phenomenological analysis were used. The
      analysis revealed an appetite for learning in order to develop an in depth
      understanding of their former experiences. This was motivated by a desire to
      master daily life despite living with an illness and to increase health and well
      being. The participants perceived the learning processes within the healthcare
      setting as mental health promoting. This craving for a better life is compatible
      with health promotion. It may turn out to be an opportunity to complement the
      curative activity of healthcare services with health promotion educational
      activities.

PMID- 29579202
TI  - Predictors of exclusive breastfeeding across three time points in Bangladesh: an
      examination of the 2007, 2011 and 2014 Demographic and Health Survey.
AB  - Background: The objective of this study was to explore predictors of exclusive
      breastfeeding (EBF) in Bangladesh using data from 2007, 2011 and 2014,
      specifically focusing on potential reasons why rates of EBF changed over those
      time periods. Methods: Data on mother/infant pairs with infants <6 months of age
      were examined at the three time points using the Bangladesh Demographic and
      Health Survey. The EBF prevalence, changes in EBF since the previous survey and
      determinants of EBF at each time period were examined using t-tests, chi2 and
      multilevel logistic regression. Results: The prevalence of EBF was 42.5, 65 and
      59.4% in 2007, 2011 and 2014, respectively. The age of the child was
      significantly associated with EBF across all time points. The largest changes in
      EBF occurred in the 3- to 5-month age group. Predictors of EBF in this specific
      age group were similar to overall predictors (e.g. age of the child and region).
      Participation of the mother in household decisions was a significant predictor in
      2014. Conclusions: EBF prevalence in Bangladesh increased between 2007 and 2011
      and then decreased between 2011 and 2014. The increase in 2011 may have been the
      result of widespread initiatives to promote EBF in that time frame. Due to the
      unexplained decrease in EBF between 2011 and 2014, there is still a need for
      interventions such as peer counselling, antenatal education and community
      awareness to promote EBF.

PMID- 29579204
TI  - Dietary diversity and nutritional status among children in rural Burkina Faso.
AB  - Background: Burkina Faso has a seasonal malnutrition pattern, with higher
      malnutrition prevalence during the rainy season when crop yields are low. We
      investigated the association between dietary diversity and nutritional status
      among children aged 6-59 mo during the low crop yield season in rural Burkina
      Faso to assess the role of dietary diversity during the lean season on childhood
      nutritional status. Methods: Caregivers reported the dietary diversity of the
      past 7 d, consisting of 11 food groups, summed into a scale. Anthropometric
      measurements were taken from all children. Height-for-age (HAZ), weight-for
      height (WHZ) and weight-for-age (WAZ) z-scores were calculated based on 2006 WHO
      standards. Stunting, wasting and underweight were defined as HAZ, WHZ and WAZ <-2
      SD, respectively. Multivariable regression models adjusting for potential
      confounders including household food insecurity and animal ownership were used to
      assess the relationship between anthropometric indices and dietary diversity.
      Results: Of 251 children enrolled in the study, 20.6% were stunted, 10.0% wasted
      and 13.9% underweight. Greater dietary diversity was associated with greater HAZ
      (SD 0.14, 95% CI 0.04 to 0.25) among all children. There was no association
      between dietary diversity and wasting or mid-upper arm circumference in this
      study. Conclusions: Increasing dietary diversity may be an approach to reduce the
      burden of stunting and chronic malnutrition among young children in regions with
      seasonal food insecurity.

PMID- 29579206
TI  - An miR-200 Cluster on Chromosome 23 Regulates Sperm Motility in Zebrafish.
AB  - Besides its well-documented roles in cell proliferation, apoptosis, and
      carcinogenesis, the function of the p53-microRNA axis has been recently revealed
      in the reproductive system. Recent studies indicated that miR-200 family members
      are dysregulated in nonobstructive azoospermia patients, whereas their functions
      remain poorly documented. The aim of this study was to investigate the function
      of the miR-200 family on zebrafish testis development and sperm activity. There
      was no substantial difference in testis morphology and histology between wild
      type (WT) and knockout zebrafish with deletion of miR-200 cluster on chromosome 6
      (chr6-miR-200-KO) or on chromosome 23 (chr23-miR-200-KO). Interestingly, compared
      with WT zebrafish, the chr6-miR-200-KO zebrafish had no difference on sperm
      motility, whereas chr23-miR-200-KO zebrafish showed significantly improved sperm
      motility. Consistently, ectopic expression of miR-429a, miR-200a, and miR-200b,
      which are located in the miR-200 cluster on chromosome 23, significantly reduced
      motility traits of sperm. Several sperm motility-related genes, such as amh,
      wt1a, and srd5a2b have been confirmed as direct targets of miR-200s on chr23.
      17alpha-ethynylestradiol (EE2) exposure resulted in upregulated expression of p53
      and miR-429a in testis and impairment of sperm motility. Strikingly, in p53
      mutant zebrafish testis, the expression levels of miR-200s on chr23 were
      significantly reduced and accompanied by a stimulation of sperm motility.
      Moreover, the upregulation of miR-429a associated with EE2 treatment was
      abolished in testis with p53 mutation. And the impairment of sperm activity by
      EE2 treatment was also eliminated when p53 was mutated. Together, our results
      reveal that miR-200 cluster on chromosome 23 controls sperm motility in a p53
      dependent manner.

PMID- 29579205
TI  - Effect of Tea Saponin-Treated Host Plants on Activities of Antioxidant Enzymes in
      Larvae of the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae).
AB  - Tea saponin (TS) is extracted from the seeds of the tea plant and is generally
      regarded as a safe compound that has insecticidal properties and can act
      synergistically with other compounds. In this study, the activities of
      antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), catalase (CAT),
      and the levels of malondialdehyde (MDA) were compared in midgut tissues of third
      instar larvae of the diamondback moth (DBM), Plutella xylostella L. (Lepidoptera:
      Plutellidae). The larvae were fed on three different host plants, cabbage
      (Brassica oleracea L. var. capitata [Capparales: Brassicaceae]), radish (Raphanus
      sativus L. var. radiculus Persi [Capparales: Brassicaceae]), or rape (Brassica
      campestris L. [Capparales: Brassicaceae]), that had been treated with TS. Higher
      SOD, POD, and CAT activities were found in DBM larvae fed on cabbage after LC20
      (concentration that induced 20% larval mortality) or LC50 (concentration that
      induced 50% larval mortality) treatment than on the control. On rape, TS
      treatments led to lower SOD and CAT activities than in the control and to higher
      POD activities after 24 h. MDA content increased in larvae fed on rape but
      decreased in larvae fed on radish after 12 h. Our results indicated that DBM
      larvae are more susceptible to TS on rape than on cabbage and radish, suggesting
      that this treatment may be an economic and effective means of controlling DBM on
      rape.

PMID- 29579207
TI  - Implementation of a human papillomavirus screen-and-treat model in Mwanza,
      Tanzania: training local healthcare workers for sustainable impact.
AB  - Background: The purpose of this study is to evaluate the development of a 1-wk
      screening campaign and efforts towards the implementation of a sustainable system
      that addresses cervical cancer in Mwanza, Tanzania with a screen-and-treat model
      utilizing visual inspection of the cervix with acetic acid (VIA) and cryotherapy.
      Methods: In partnership with CureCervicalCancer (CCC), a non-profit organization
      based in Los Angeles, CA, USA, 11 medical students at the University of
      California, Irvine School of Medicine established a model for sustainable human
      papillomavirus screening practices in Mwanza, Tanzania. This study both
      quantitatively and qualitatively assesses the successes and limitations of the
      program model. Results: During the 5-day training, a total of 614 women attended
      the screenings and 556 women were screened with VIA, of whom 10.6% (n=59) were
      VIA positive and 89.4% (n=499) were VIA negative. Of those who were VIA positive,
      83.1% (n=49) received cryotherapy while 16.9% (n=10) did not due to suspicion of
      advanced cancer (n=7), refusal to receive cryotherapy (n=2) or pregnancy (n=1).
      Conclusions: The screen-and-treat model for the identification and treatment of
      precancerous cervical lesions is an effective public health intervention with the
      potential to impact women by providing the tools and education needed by local
      healthcare professionals. However, limitations common to resource-poor settings,
      such as continuity of funding, loss to follow-up and transportation costs, remain
      barriers to sustainability.

PMID- 29579208
TI  - Earthworms are associated with subpopulations of Gammaproteobacteria irrespective
      of the total soil microbiota composition and stability.
AB  - Soil represents one of the most complex microbial ecosystems on earth. It is well
      known that invertebrates such as earthworms have a major impact on
      transformations of organic material in soil, while their effect on the soil
      microbiota remains largely unknown. The aim of our work was therefore to
      investigate the association of earthworms with temporal stability, composition
      and diversity in two soil microbiota experimental series. We found that
      earthworms were consistently associated with an increase in subgroups of
      Gammaproteobacteria, despite major differences in microbiota composition and
      temporal stability across the experimental series. Our results therefore suggest
      that earthworms can affect subpopulation dynamics in the soil microbiota,
      irrespective of the total microbiota composition. If the soil microbiota is
      comprised of independent microbiota components, this can contribute to our
      general understanding of the complexity of the soil microbiota.

PMID- 29579210
TI  - Changes in prescription pattern, pharmaceutical expenditure and quality of care
      after introduction of reimbursement restriction in diabetes in Korea.
AB  - Background: To ensure effective prescription practices and reduce diabetes
      related pharmaceutical expenditures, Korea adopted a clinical practice guideline
      for the reimbursement system. Health care providers cannot receive reimbursement
      from National Health Insurance(NHI) unless it is for an appropriate prescription
      under the predefined clinical condition. The aim of this study was to evaluate
      prescription patterns in oral hypoglycemic agents, costs and effects on patient
      care since the introduction of the diabetes reimbursement restriction. Methods:
      We used claim data from 2008 to 2013, which included 26 315 diabetes patients and
      9907 hospitals. An interrupted time series study design using generalized
      estimating equations was used to evaluate changes in patterns of single and
      combination therapy, brand name drug prescriptions, cost and hospital admission
      following the reimbursement restriction. Results: Following reimbursement
      restriction initiation, we found a statistically significant decrease in the
      average prescription rate of brand name drugs (-6.2%), whereas single therapy
      prescription increased (9.9%). There was also a reduction in trend change in the
      monthly prescription rate for combination therapy (-1.7%) and brand name drugs (
      0.8%). For single therapy, the trend change in prescription rate increased after
      the intervention (0.8%). A reduction of trend change in pharmaceutical costs (
      0.3%) was observed. However, we did not find a significant change in hospital
      admission for diabetes. Conclusions: Reimbursement restriction affects both
      pharmaceutical costs and physicians' decisions to prescribe oral hypoglycemic
      agents. We did not observe a significant reduction in quality of care following
      the intervention. Collectively, these findings indicate that reimbursement
      restriction has improved effective drug utilization and decreased health
      expenditures.

PMID- 29579209
TI  - Does minimally invasive coronary artery bypass improve outcomes compared to off
      pump coronary bypass via sternotomy in patients undergoing coronary artery bypass
      grafting?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'In patients undergoing off-pump coronary
      artery bypass grafting, for single or multivessel disease, does minimally
      invasive direct coronary artery bypass (MIDCAB) or off-pump coronary artery
      bypass (OPCAB) provide the superior outcome including a reduction in morbidity
      and mortality?'. A total of 187 papers were found using the reported search, of
      which 12 represented the best evidence to answer the clinical question. The
      authors, date, journal and country of publication, patient group studied, study
      type, relevant outcomes and results of these papers are tabulated. It was found
      that compared to OPCAB, MIDCAB surgery can offer decreased intensive care unit
      length of stay (4.5-57.4 h vs 5.2-52.7 h) and total hospital length of stay (4.5
      8.5 days vs 5.2-12 days), with 1 paper showing a decrease in mortality at 1 year
      (3% vs 14%). However, there were several papers that showed significant risks
      with MIDCAB surgery in patients with either single or multivessel disease. These
      include increased risk of incomplete revascularization (29% vs 0%), significant
      early complications (22.5 vs 0%), urgent reintervention (16% vs 0%), repeat
      revascularization events (12.2% vs 3.7%), progression of native disease (4.8% vs
      0.9%), rehospitalization by 3 months (20% vs 2%) and postoperative infarction
      (2.9% vs 1.45%). These risks did not translate to an increase in early mortality
      (0-1% vs 0-1.6%) or late mortality (0-3% vs 0-14%) in papers that included mid
      term follow up. However, they do represent significant potential risks that
      cannot be overlooked when considering the use of MIDCAB. We conclude that MIDCAB
      is associated with greater morbidity and reintervention compared to OPCAB via
      sternotomy, but both techniques are equivalent in terms of operative and mid-term
      mortality.

PMID- 29579211
TI  - The trials of trials: RCTs to assess causal questions about social interventions.

PMID- 29579212
TI  - Introduction: Food as Medicine, Medicine as Food.

PMID- 29579213
TI  - Global aspects of viral glycosylation.
AB  - Enveloped viruses encompass some of the most common human pathogens causing
      infections of different severity, ranging from no or very few symptoms to lethal
      disease as seen with the viral hemorrhagic fevers. All enveloped viruses possess
      an envelope membrane derived from the host cell, modified with often heavily
      glycosylated virally encoded glycoproteins important for infectivity, viral
      particle formation and immune evasion. While N-linked glycosylation of viral
      envelope proteins is well characterized with respect to location, structure and
      site occupancy, information on mucin-type O-glycosylation of these proteins is
      less comprehensive. Studies on viral glycosylation are often limited to analysis
      of recombinant proteins that in most cases are produced in cell lines with a
      glycosylation capacity different from the capacity of the host cells. The
      glycosylation pattern of the produced recombinant glycoproteins might therefore
      be different from the pattern on native viral proteins. In this review, we
      provide a historical perspective on analysis of viral glycosylation, and
      summarize known roles of glycans in the biology of enveloped human viruses. In
      addition, we describe how to overcome the analytical limitations by using a
      global approach based on mass spectrometry to identify viral O-glycosylation in
      virus-infected cell lysates using the complex enveloped virus herpes simplex
      virus type 1 as a model. We underscore that glycans often pay important
      contributions to overall protein structure, function and immune recognition, and
      that glycans represent a crucial determinant for vaccine design. High throughput
      analysis of glycosylation on relevant glycoprotein formulations, as well as data
      compilation and sharing is therefore important to identify consensus
      glycosylation patterns for translational applications.

PMID- 29579214
TI  - Temocillin dosing in haemodialysis patients based on population pharmacokinetics
      of total and unbound concentrations and Monte Carlo simulations.
AB  - Objectives: To develop a population model describing temocillin pharmacokinetics
      (PK) in patients undergoing haemodialysis and investigate how
      pharmacokinetic/pharmacodynamic (PD) targets can be met with different dosage
      regimens. Patients and methods: Sixteen patients received the currently licenced
      dosing of 1, 2 or 3 g of temocillin (total of 61 doses) corresponding to an inter
      dialytic period of 20, 44 or 68 h, respectively, and a dialysis period of 4 h. A
      non-linear mixed-effects model was developed jointly for total and unbound
      temocillin serum concentrations. The performance of clinically feasible dosing
      regimens was evaluated using a 5000-subject Monte Carlo (MC) simulation for
      determining the highest MIC for which the PK/PD target of 40%fT>MIC would be
      reached in 90% of patients [probability of target attainment (PTA)]. This PK
      study was registered at ClinicalTrials.gov (NCT02285075). Results: Temocillin
      unbound and total serum concentrations (429 samples) were used to fit an open two
      compartment model with non-linear albumin binding and first-order elimination. In
      addition to total body clearance, dialysis clearance was modelled using the
      Michaels function. The currently licenced dosing achieved a 90% PTA for an MIC up
      to 8 mg/L. A new temocillin dosage regimen was designed that would achieve a 90%
      PTA for an MIC of 16 mg/L (MIC90 of target organisms) adjusted to patient weight
      and inter-dialytic period. Conclusions: Currently licensed dosage regimen is
      suboptimal for MICs >8 mg/L (frequently found in clinical isolates). Model-based
      simulations allowed suggestion of a new dosage regimen with improved probability
      of microbiological success, applicability in routine clinical practice and more
      appropriate for empirical therapy.

PMID- 29579215
TI  - Variations in the relative abundance of Wolbachia in the gut of Nasutitermes
      arborum across life stages and castes.
AB  - There are multiple forms of interactions between termites and bacteria. In
      addition to their gut microbiota, which has been intensively studied, termites
      host intracellular symbionts such as Wolbachia. These distinct symbioses have
      been so far approached independently and mostly in adult termites. We addressed
      the dynamics of Wolbachia and the microbiota of the eggs and gut for various life
      stages and castes of the wood-feeding termite, Nasutitermes arborum, using deep
      sequencing of the 16S rRNA gene. Wolbachia was dominant in eggs as expected.
      Unexpectedly, it persisted in the gut of nearly all stages and castes, indicating
      a wide somatic distribution in termites. Wolbachia-related sequences clustered
      into few operational taxonomic units, but these were within the same genotype,
      acquired maternally. Wolbachia was largely dominant in DNA extracts from the guts
      of larvae and pre-soldiers (59.1%-99.1% of reads) where gut-resident lineages
      were less represented and less diverse. The reverse was true for the adult
      castes. This is the first study reporting the age-dependency of the relative
      abundance of Wolbachia in the termite gut and its negative correlation with the
      diversity of the microbiota. The possible mechanisms underlying this negative
      interaction are discussed.

PMID- 29579216
TI  - Acinetobacter baumannii Resistance Trends in Children in the United States, 1999
      2012.
AB  - Background: Acinetobacter baumannii is a common cause of healthcare-associated
      infections. Carbapenem-resistant (CR) A baumannii is a significant threat
      globally. We used a large reference laboratory database to study the epidemiology
      of A baumannii in children in the United States. Methods: Antimicrobial
      susceptibility data from The Surveillance Network were used to phenotypically
      identify antibiotic resistance in A baumannii isolates in children 1-17 years of
      age between January 1999 and July 2012. Logistic regression analysis was used to
      calculate trends in the prevalence of antibiotic resistance in A baumannii.
      Isolates from infants (<1 year old) were excluded. Results: The crude proportion
      of cephalosporin-resistant (CephR) A baumannii increased from 13.2% in 1999 to
      23.4% in 2012 with a peak of 32.5% in 2008, and the proportion of CR A baumannii
      increased from 0.6% in 1999 to 6.1% in 2012 with a peak of 12.7% in 2008. From
      1999 to 2012, the proportion of CephR and CR A baumannii increased each year by
      3% and 8%, respectively (CephR odds ratio [OR] = 1.03, 95% confidence interval
      [CI], 1.01-1.04; CR OR = 1.08, 95% CI, 1.05-1.12); however, after 2008, a
      significant decrease in trend was observed (CephR OR = 0.78, 95% CI, 0.71-0.87;
      CR OR = 0.73, 95% CI, 0.62-0.86), but resistance remained higher than baseline
      (1999). Conclusions: Overall, between 1999 and 2012, CephR and CR A baumannii
      isolates increased in children; however, a decreasing trend was observed after
      2008.There is a need for ongoing surveillance of A baumannii infections and
      continued assessment of effective prevention strategies in vulnerable
      populations.

PMID- 29579217
TI  - Nursing and Hospital Abortions in the United States, 1967-1973.
AB  - Before elective abortion was legalized nationally in 1973 with the U.S. Supreme
      Court decision Roe v. Wade, seventeen states and the District of Columbia
      liberalized their abortion statutes. While scholars have examined the history of
      physicians who had performed abortions before and after it was legal and of
      feminists' work to expand the range of healthcare choices available to women, we
      know relatively little about nurses' work with abortion. By focusing on the
      history of nursing in those states that liberalized their abortion laws before
      Roe, this article reveals how women who sought greater control over their lives
      by choosing abortion encountered medical professionals who were only just
      beginning to question the gendered conventions that framed labor roles in
      American hospitals. Nurses, whose workloads increased exponentially when abortion
      laws were liberalized, were rarely given sufficient training to care for abortion
      patients. Many nurses directed their frustrations to the women patients who
      sought the procedure. This essay considers how the expansion of women's right to
      abortion prompted nurses to question the gendered conventions that had shaped
      their work experiences.

PMID- 29579218
TI  - Social and community factors associated with hypertension awareness and control
      among older adults in Tirana, Albania.
AB  - Background: Determinants of hypertension diagnosis and/or awareness and control
      among older adults are understudied in Albania, a former communist country in
      South Eastern Europe, which is experiencing rapid demographic, socioeconomic and
      epidemiological transition. This paper examines the association of individual,
      interpersonal, organizational and community factors with hypertension awareness
      and control among older adults in Tirana, the Albanian capital. Methods: Using
      2012 International Mobility in Aging Study data on older adults from Albania's
      capital city (n = 393) and the socioecological model as a conceptual framework,
      multinomial regression models identified factors associated with controlled,
      uncontrolled and undiagnosed hypertension. Results: For hypertension, 17.3%
      participants had none, 23.4% were controlled, 48.4% were uncontrolled and 10.9%
      were undiagnosed/unaware. Compared to those with controlled hypertension, in
      multivariable models, a high level of friend support was negatively associated
      with uncontrolled (OR: 0.4; 95% CI: 0.2-0.9) and undiagnosed (OR: 0.2; 95% CI:
      0.1-0.6) hypertension. A high level of perceived neighbourhood safety was
      negatively associated with uncontrolled (OR: 0.6; 95% CI: 0.3-1.0) and
      undiagnosed (OR: 0.4; 95% CI: 0.2-1.0) hypertension. Compared to those with no
      hypertension, children's social support was positively associated with
      uncontrolled (OR: 2.2; 95% CI: 1.1-4.3) and undiagnosed (OR: 3.6; 95% CI: 1.3
      9.6) hypertension. Conclusion: This study provides new insights about distinct
      risk factors for inadequate hypertension management in Albania. It highlights the
      importance of community-level factors (safety) and interpersonal factors (family
      and friend ties) to hypertension diagnosis/awareness and control, which may
      provide novel intervention opportunities for hypertension programs.

PMID- 29579219
TI  - Operator volume is not associated with mortality following percutaneous coronary
      intervention: insights from the British Cardiovascular Intervention Society
      registry.
AB  - Aims: The relationship between operator volume and outcomes for percutaneous
      coronary intervention (PCI) has been studied in the past, but recent analyses of
      national data covering the modern radial, acute coronary syndrome-dominant era
      are limited. Changing in case-mix, practice, and service provision mean that
      previously described volume-outcome relationships may no longer be relevant, and
      a reassessment in contemporary practice is needed. We aim to assess whether
      operator volume is associated with independently reported 30-day mortality in a
      contemporary PCI cohort. Methods and results: This observational cohort study
      analysed procedures recorded in the British Cardiovascular Intervention Society
      PCI database from 2013 to 2014 in England and Wales. Mixed effects multiple
      logistic regression modelling was used to account for operator and centre level
      effects and to adjust for potential confounders. Volume is defined as the total
      number of procedures the operator was responsible for in the previous 12 months.
      A total of 133 970 procedures were analysed. Median volume across all procedures
      was 178 per year (interquartile range 128-239). The 30-day mortality rate was
      2.6%. After adjustment for case-mix, the association between volume and mortality
      was negligible (odds ratio per 100 procedures 0.99, 95% confidence interval 0.93
      1.05; P = 0.725). Sensitivity analyses showed similar results amongst high-risk
      PCI subsets and in-hospital outcomes. Conclusion: There is no evidence that
      mortality differs by operator volume in the UK. Volume-outcome relationships in
      PCI should be carefully monitored in response to future changes in practice.

PMID- 29579220
TI  - Insufficient physical activity in combination with high screen time is associated
      with adolescents' psychosocial difficulties.
AB  - Background: Although screen time (ST) and insufficient physical activity (PA) are
      fairly common among adolescents, it is unclear whether these conditions are
      jointly associated with adolescents' psychosocial difficulties. This study aimed
      to examine interactive associations of ST and PA with psychosocial difficulties
      among adolescents in Bangladesh. Methods: Data were from 671 students (ages 13-16
      y) from eight secondary schools of Dhaka City, Bangladesh. Recreational ST was
      assessed using the Adolescent Sedentary Activity Questionnaire. The 3-day
      Physical Activity Recall instrument was used to estimate PA. Psychosocial
      difficulty was measured using the parent version of the Strengths and
      Difficulties Questionnaire (SDQ). Results: Sixteen percent of the adolescents had
      high SDQ total difficulties scores (>=17) and another 14% had moderate scores (14
      16; borderline). Multivariable modelling showed that adolescents with high ST (>2
      h/day) and insufficient PA (<60 min/day; not meeting the PA recommendation) had
      more psychosocial difficulties than their counterparts who had low ST and met PA
      recommendations (p=0.03). The analysis also found marginal evidence (p=0.06) of
      an association with psychosocial difficulties for adolescents with insufficient
      PA and low ST. Conclusions: Adolescents in Dhaka City who have high recreational
      ST and are not meeting PA recommendations are likely to also have psychosocial
      difficulties. Longitudinal studies are needed to understand the causal
      relationships between these variables.

PMID- 29579221
TI  - Prolonged dialysis duration is associated with graft failure and mortality after
      kidney transplantation: results from the French transplant database.
AB  - Background: Kidney transplantation (KT) is the treatment of choice for end-stage
      renal disease. Preemptive KT (PKT) should be considered when glomerular
      filtration rate is <15 mL/min/1.73 m2 but European reports on the results of PKT
      and the effect of pretransplant dialysis are scarce. Methods: We analysed all
      first kidney-only transplants performed in adults in France between 2002 and
      2012. A Cox multivariable model was used to investigate the association of PKT
      and of pretransplant dialysis time with the hazard of graft failure defined as
      death, return to dialysis or retransplant, whichever occurred first. Results: We
      included 22 345 patients, with a mean +/- SD age at KT of 50.5 +/- 13.4 years;
      61.9% were men and 3112 (14.0%) received a PKT. Median time of follow-up was 4.7
      years. Graft failure occurred in 4952 patients up to 31 December 2013. After
      adjustment for recipients' age and sex, primary kidney disease, donor type
      (living or deceased donor, expanded criteria donor), HLA mismatches, cold
      ischaemia time, centre and year of transplantation, PKT was associated with a
      decreased hazard of graft failure when compared with pretransplant dialysis
      [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.51-0.63], whatever the
      duration of dialysis, even in the first 6 months. The effect of PKT on the hazard
      of graft failure was stronger in living kidney donors (HR 0.32; 95% CI 0.19
      0.55). Conclusions: In France, PKT was associated with a lower risk of graft
      failure than KT performed after the initiation of dialysis, whatever the duration
      of dialysis.

PMID- 29579223
TI  - Assessment of a congenital heart surgery programme: a reappraisal.
AB  - OBJECTIVES: To assess our practice according to the Society of Thoracic Surgeons
      and the European Association for Cardio-Thoracic Surgery (STS-EACTS) Mortality
      Score and to the new concept of unit performance. METHODS: All main procedures
      carried out in the years 2012-2016 were analysed. The STS-EACTS model-based
      mortality risk procedure was used to calculate expected mortality. Surgical
      performance was estimated as the Aristotle complexity score multiplied by
      hospital survival. Unit performance was defined as surgical performance
      multiplied by the number of procedures. RESULTS: In total, 2435 procedures were
      analysed. One hundred and two deaths (95% confidence interval 71-135 deaths) were
      expected; 43 patients died after operation. Observed mortality divided by
      expected mortality was 0.42. The ratio ranged from 0.23 (year 2014) to 0.59 (year
      2013) and was <0.6 in all STS-EACTS mortality categories. The difference between
      observed and expected mortality was highly significant: 1.8% vs 4.2% (P-value
      <0.0001). Observed surgical and unit performances were, higher than expected
      performances every year. Achieved surgical performance was the highest in year
      2012 (7.28 +/- 2.54) and the lowest in year 2014 (7.04 +/- 2.52). The highest
      figure of unit performance was achieved in year 2016: 3980 points. CONCLUSIONS:
      The STS-EACTS score, currently recognized as a sound instrument to assess
      mortality after congenital heart surgery, overestimated postoperative mortality.
      If these results are confirmed by other centres, the model should be recalibrated
      to match the current surgical practice. Although surgical performance can
      evaluate outcome quality, it does not include case volume activity. Unit
      performance provides this information, and it integrates quality and quantity
      into a single value.

PMID- 29579222
TI  - Inhibition of fatty acid amide hydrolase by PF-3845 alleviates the nitrergic and
      proinflammatory response in rat hippocampus following acute stress.
AB  - Background: Long term exposure to stress has been demonstrated to cause
      neuroinflammation through a sustained overproduction of free radicals, including
      nitric oxide, via an increased inducible nitric oxide synthase (iNOS) activity.
      We have previously demonstrated that iNOS activity and mRNA are significantly
      upregulated in the rat hippocampus following just 4 hours of restraint stress.
      Similar to nitric oxide, endocannabinoids are synthesised on demand, with
      preclinical observations suggesting that cannabinoid receptor agonists and
      endocannabinoid enhancers inhibit nitrergic activity. Specifically, previous work
      has shown that enhancement of endocannabinoids via inhibition of fatty acid amide
      hydrolase with PF-3845 reduced iNOS-expressing microglia following traumatic
      brain injury. However, this describes cannabinoid modulation following physical
      injury and therefore the present study aimed to examine the effects of PF-3845 in
      the modulation of nitrergic and inflammatory-related genes within the hippocampus
      after acute stress exposure. Methods: Following vehicle or PF-3845 injections (5
      mg/kg; i.p.), male Wistar rats were exposed to 0 (control), 60, 240, or 360
      minutes of restraint stress after which plasma and dorsal hippocampus were
      isolated for further biochemical and gene expression analysis. Results: The
      results demonstrate that pre-treatment with PF-3845 rapidly ameliorates plasma
      corticosterone release at 60 minutes of stress. An increase in endocannabinoid
      signalling also induces an overall attenuation in iNOS, tumor necrosis factor
      alpha convertase, interleukin-6, cyclooxygenase-2, peroxisome proliferator
      activated receptor gamma mRNA, and the transactivation potential of NF-kappaB in
      the hippocampus. Conclusions: These results suggest that enhanced endocannabinoid
      levels in the dorsal hippocampus have an overall anti-nitrosative and anti
      inflammatory effect following acute stress exposure.

PMID- 29579224
TI  - Comprehensive analysis of Helicobacter pylori infection-associated diseases based
      on miRNA-mRNA interaction network.
AB  - Helicobacter pylori (H. pylori) infection remains a cause of significant
      morbidity and mortality worldwide. Comprehensive understanding of the pathogenic
      mechanism of H. pylori and its interaction with host will contribute to
      developing novel prophylactical and therapeutical strategies. Here, we first
      determined microRNA (miRNA) levels in H. pylori-infected patients with gastritis,
      duodenal ulcer, gastric cancer or mucosa-associated lymphoid tissue lymphoma
      using miRNA data sets. Thirty-four differentially expressed miRNAs were
      identified and functional enrichment analysis of those miRNA target genes
      revealed that H. pylori infection were strongly associated with pathway in cancer
      and regulation of mRNA synthesis. Using disease connectivity analysis of 28 hub
      genes, we found that H. pylori may increase the risk of many extragastric
      diseases (e.g. cardiovascular disease, hemic and lymphatic diseases and nervous
      system disease). Altogether, our integrated analysis provided a new method to
      predict pathogen-human disease connectivity based on miRNA-mRNA interaction
      network and indicated anti-H. pylori therapy as an effective means of human
      diseases prevention.

PMID- 29579226
TI  - CEP peptide hormones: key players in orchestrating nitrogen-demand signalling,
      root nodulation, and lateral root development.
AB  - Secreted peptide hormones play pivotal roles in plant growth and development. So
      far, CEPs (C-TERMINALLY ENCODED PEPTIDEs) have been shown to act through CEP
      receptors (CEPRs) to control nitrogen (N)-demand signalling, nodulation, and
      lateral root development. Secreted CEP peptides can enter the xylem stream to act
      as long-distance signals, but evidence also exists for CEPs acting in local
      circuits. Recently, CEP peptide species varying in sequence, length, and post
      translational modifications have been identified. A more comprehensive
      understanding of CEP biology requires insight into the in planta function of CEP
      genes, CEP peptide biogenesis, the components of CEP signalling cascades and,
      finally, how CEP peptide length, amino-acid composition, and post-translational
      modifications affect biological activity. In this review, we highlight recent
      studies that have advanced our understanding in these key areas and discuss some
      future directions.

PMID- 29579225
TI  - Distinct telomere length and molecular signatures in seminoma and non-seminoma of
      testicular germ cell tumor.
AB  - Testicular germ cell tumors (TGCTs) are classified into two main subtypes,
      seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain
      largely unexplored. Here, we used expression data for mRNAs and microRNAs
      (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic
      investigation to explain the different telomere length (TL) features between NSE
      (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE,
      whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA
      expression profiles could clearly distinguish these two subtypes. Notably, four
      telomere-related genes (TelGenes) showed significantly higher expression and
      positively correlated with telomere elongation in NSE than SE: three telomerase
      activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase
      activity gene (ZSCAN4). We also found that the expression of genes encoding
      Yamanaka factors was positively correlated with telomere lengthening in NSE.
      Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and
      KLF4 had the opposite patterns. These results suggested that enhanced expression
      of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce
      telomere elongation in NSE. Conversely, the relative lack of telomerase
      activation and low expression of independent telomerase activity pathway during
      cell division may be contributed to telomere shortening in SE. Taken together,
      our results revealed the potential molecular profiles and regulatory roles
      involving the TL difference between NSE and SE, and provided a better molecular
      understanding of this complex disease.

PMID- 29579227
TI  - Endovascular repair of a subclavian artery aneurysm in Behcet's disease.
AB  - Behcet's disease is a rare, chronic, relapsing condition comprising multisystemic
      inflammatory dysfunction, whereas subclavian artery aneurysm is a rare peripheral
      atherosclerotic aneurysm that has a high risk of rupture or embolization. Herein,
      we report the case of a 32-year-old man with Behcet's disease who developed
      pseudoaneurysm of the left subclavian artery. He was admitted to the emergency
      department due to radiating pain in the left neck and shoulder. Endovascular
      repair was performed, and high-dose anti-inflammatory therapy was begun.
      Ultrasonography performed on postoperative day 3 showed good stent patency.
      Endovascular therapy may be a safe and effective treatment for arterial aneurysm
      in patients with Behcet's disease.

PMID- 29579228
TI  - Andre Simon, cardiac & transplant surgeon.

PMID- 29579229
TI  - The new SFB/TRR219 Research Centre.

PMID- 29579230
TI  - Ferrara V.

PMID- 29579231
TI  - Ebstein's or Prescher's Anomaly?

PMID- 29579232
TI  - Guidelines for Composing and Assessing a Paper on the Treatment of Pain: A
      Practical Application of Evidence-Based Medicine Principles to the Mint
      Randomized Clinical Trials.
AB  - Objective: To perform a thorough assessment of the recently published Mint Trials
      in order to illustrate how to read and analyze a study critically, according to
      principles of evidence-based medicine. Design: Narrative review. Method: We have
      applied the recently published guidelines for composing and assessing studies on
      the treatment of pain to a recently published article describing a large study
      that claimed its "findings do not support the use of radiofrequency denervation
      to treat chronic low back pain." These guidelines describe the critical
      components of a high-quality manuscript that allows communication of all relevant
      information from authors to readers. Results: Application of evidence-based
      medicine principles to the publication describing the Mint Trials reveals
      significant issues with the methodology and conclusions drawn by the authors. A
      thorough assessment demonstrates issues with inclusion/exclusion criteria,
      diagnostic block protocols, radiofrequency neurotomy technique, co-interventions,
      outcome measurement, power analysis, study sample characteristics, data analysis,
      and loss to follow-up. A failure to definitively establish a diagnosis, combined
      with use of an inadequate technique for radiofrequency neurotomy and numerous
      other methodological flaws, leaves the reader unable to draw meaningful
      conclusions from the study data. Conclusions: Critical analysis, rooted in
      principles of evidence-based medicine, must be employed by writers and readers
      alike in order to encourage transparency and ensure that appropriate conclusions
      are drawn from study data.

PMID- 29579233
TI  - Systematic Review and Meta-Analysis to Assess the Safety of Buproprion and
      Varenicline in Pregnancy.
AB  - Introduction: Smoking in pregnancy is a substantial public health issue, but,
      apart from nicotine replacement therapy (NRT), pharmacological therapies are not
      generally used to promote cessation. Bupropion and varenicline are effective
      cessation methods in non-pregnant smokers and this systematic review investigates
      their safety in pregnancy. Methods: We searched MEDLINE, EMBASE, CINAHL and
      PsychINFO databases for studies of any design reporting pregnancy outcomes after
      bupropion or varenicline exposure. We included studies of bupropion used for
      smoking cessation, depression, or where the indication was unspecified. Depending
      on study design, quality was assessed using the Newcastle-Ottawa Scale or
      Cochrane Risk of Bias Tool. Most findings are reported narratively but meta
      analyses were used to produce pooled estimates for the proportion of live births
      with congenital malformations and of the mean birthweight and gestational age at
      delivery following bupropion exposure. Results: 18 studies were included: two
      randomised controlled trials, eleven cohorts, two case-control studies and three
      case reports. Study quality was variable. Gestational safety outcomes were
      reported in 14 bupropion and four varenicline studies. Meaningful meta-analysis
      was only possible for bupropion exposure, for which the pooled estimated
      proportion of congenital malformations amongst live-born infants was 1.0% (95%
      CI= 0.0-3.0%, I2= 80.9%, 4 studies) and the mean birthweight and mean gestational
      age at delivery was 3305.9g (95% CI= 3173.2-3438.7g, I2= 77.6%, 5 studies) and
      39.2 weeks (95% CI= 38.8-39.6, I2= 69.9%, 5 studies) respectively. Conclusions:
      There was no strong evidence that either major positive or negative outcomes were
      associated with gestational use of bupropion or varenicline. PROSPERO
      registration number CRD42017067064. Implications: We believe this to be the first
      systematic review investigating the safety of bupropion and varenicline in
      pregnancy. Meta-analysis of outcomes following bupropion exposure in pregnancy
      suggests that there are no major positive or negative impacts on the rate of
      congenital abnormalities, birthweight or premature birth. Overall, we found no
      evidence that either of these treatments might be harmful in pregnancy, and no
      strong evidence to suggest safety, but available evidence is of poor quality.

PMID- 29579235
TI  - Duodenoscope-Related Outbreak of a Carbapenem-Resistant Klebsiella pneumoniae
      Identified Using Advanced Molecular Diagnostics.
AB  - Background: Carbapenem-resistant Klebsiella pneumoniae infections are
      increasingly prevalent in North American hospitals. We describe an outbreak of
      carbapenem-resistant K. pneumoniae containing the blaOXA-232 gene transmitted by
      contaminated duodenoscopes during endoscopic retrograde cholangiopancreatography
      (ERCP) procedures. Methods: An outbreak investigation was performed when 9
      patients with blaOXA-232 carbapenem-resistant K. pneumoniae infections were
      identified at a tertiary care hospital. The investigation included 2 case-control
      studies, review of duodenoscope reprocessing procedures, and culture of devices.
      Carbapenem-resistant Enterobacteriacieae (CRE) isolates were evaluated with
      polymerase chain reaction analysis for carbapenemase genes, and isolates with the
      blaOXA-232 gene were subjected to whole-genome sequencing and chromosome single
      nucleotide polymorphism analysis. On recognition of ERCP as a key risk factor for
      infection, targeted patient notification and CRE screening cultures were
      performed. Results: Molecular testing ultimately identified 17 patients with
      blaOxa-232 carbapenem-resistant K. pneumoniae isolates, including 9 with
      infections, 7 asymptomatic carriers who had undergone ERCP, and 1 additional
      patient who had been hospitalized in India and was probably the initial carrier.
      Two case-control studies established a point-source outbreak associated with 2
      specific duodenoscopes. A field investigation of the use, reprocessing, and
      storage of deuodenoscopes did not identify deviations from US Food and Drug
      Administration or manufacturer recommendations for reprocessing. Conclusions:
      This outbreak demonstrated the previously underappreciated potential for
      duodenoscopes to transmit disease, even after undergoing high-level disinfection
      according to manufacturers' guidelines.

PMID- 29579234
TI  - Community-led comparative genomic and phenotypic analysis of the aquaculture
      pathogen Pseudomonas baetica a390T sequenced by Ion semiconductor and Nanopore
      technologies.
AB  - Pseudomonas baetica strain a390T is the type strain of this recently described
      species and here we present its high-contiguity draft genome. To celebrate the
      16th International Conference on Pseudomonas, the genome of P. baetica strain
      a390T was sequenced using a unique combination of Ion Torrent semiconductor and
      Oxford Nanopore methods as part of a collaborative community-led project. The use
      of high-quality Ion Torrent sequences with long Nanopore reads gave rapid, high
      contiguity and -quality, 16-contig genome sequence. Whole genome phylogenetic
      analysis places P. baetica within the P. koreensis clade of the P. fluorescens
      group. Comparison of the main genomic features of P. baetica with a variety of
      other Pseudomonas spp. suggests that it is a highly adaptable organism, typical
      of the genus. This strain was originally isolated from the liver of a diseased
      wedge sole fish, and genotypic and phenotypic analyses show that it is tolerant
      to osmotic stress and to oxytetracycline.

PMID- 29579236
TI  - Improvements in Rhynchophorus ferrugineus (Coleoptera: Dryophthoridae) Trapping
      Systems.
AB  - Improved trap efficacy is crucial for implementing control methods for red palm
      weevil, Rhynchophorus ferrugineus (Olivier; Coleoptera: Dryophthoridae), based on
      trapping systems, such as mass trapping, attract and infect or attract and
      sterilize techniques. Although new trap designs have been proposed and
      aggregation pheromone dispensers have been optimized, aspects such as the use of
      co-attractants (molasses) and trap placement are still not well defined and
      standardized. The efficacy of three concentrations of molasses and different
      formulations to reduce water evaporation in traps was studied in different field
      trials to improve trapping systems and to prolong trap servicing periods. In
      addition, the performance of installing groups of traps or single traps was also
      evaluated with the aim of improving the attracted/captured weevils ratio. Our
      results showed that captures increased when molasses were added at 15% to the
      water contained in the trap and that a thin layer of oil, created by adding 2-3%
      of paraffinic oil to water, was able to effectively reduce evaporation and
      prolong trap servicing periods. Moreover, 3.5-fold more weevils were captured
      when placing five traps instead of one at the same trapping point. Results
      obtained allow improved efficacy and may have an impact in the economic viability
      of trapping systems and, therefore, in integrated pest management programs.

PMID- 29579238
TI  - Pulmonary Colonization Resistance to Pathogens via Noncanonical Wnt and
      Interleukin-17A by Intranasal pep27 Mutant Immunization.
AB  - Background: Previous studies have focused on colonization resistance of the gut
      microbiota against antibiotic resistant strains. However, less research has been
      performed on respiratory colonization resistance. Methods: Because respiratory
      colonization is the first step of respiratory infections, intervention to prevent
      colonization would represent a new approach for preventive and therapeutic
      measures. The Th17 response plays an important role in clearance of respiratory
      pathogens. Thus, harnessing the Th17 immune response in the mucosal site would be
      an effective method to design a respiratory mucosal vaccine. Results: In this
      study, we show that intranasal Deltapep27 immunization induces noncanonical Wnt
      and subsequent interleukin (IL)-17 secretion, and it inhibits Streptococcus
      pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae colonization.
      Moreover, IL-17A neutralization or nuclear factor of activated T-cell inhibition
      augmented bacterial colonization, indicating that noncanonical Wnt signaling is
      involved in pulmonary colonization resistance. Conclusions: Therefore, Deltapep27
      immunization can provide nonspecific respiratory colonization resistance via
      noncanonical Wnt signaling and IL-17A-related pathways.

PMID- 29579237
TI  - Acid ceramidase inhibition ameliorates alpha-synuclein accumulation upon loss of
      GBA1 function.
AB  - GBA1 encodes the lysosomal enzyme beta-glucocerebrosidase (GCase) which converts
      glucosylceramide into ceramide and glucose. Mutations in GBA1 lead to Gaucher's
      disease and are a major risk factor for Parkinson's disease (PD) and Dementia
      with Lewy bodies (DLB), synucleinopathies characterized by accumulation of
      intracellular alpha-synuclein. In this study, we examined whether decreased
      ceramide that is observed in GCase-deficient cells contributes to alpha-synuclein
      accumulation. We demonstrated that deficiency of GCase leads to a reduction of
      C18-ceramide species and altered intracellular localization of Rab8a, a small
      GTPase implicated in secretory autophagy, that contributed to impaired secretion
      of alpha-synuclein and accumulation of intracellular alpha-synuclein. This
      secretory defect was rescued by exogenous C18-ceramide or chemical inhibition of
      lysosomal enzyme acid ceramidase that converts lysosomal ceramide into
      sphingosine. Inhibition of acid ceramidase by carmofur resulted in increased
      ceramide levels and decreased glucosylsphingosine levels in GCase-deficient
      cells, and also reduced oxidized alpha-synuclein and levels of ubiquitinated
      proteins in GBA1-PD patient-derived dopaminergic neurons. Together, these results
      suggest that decreased ceramide generation via the catabolic lysosomal salvage
      pathway in GCase mutant cells contributes to alpha-synuclein accumulation,
      potentially due to impaired secretory autophagy. We thus propose that acid
      ceramidase inhibition which restores ceramide levels may be a potential
      therapeutic strategy to target synucleinopathies linked to GBA1 mutations
      including PD and DLB.

PMID- 29579239
TI  - Ileal digestibility of amino acids in selected feed ingredients fed to young
      growing pigs.
AB  - An experiment was conducted to determine the standardized ileal digestibility
      (SID) of CP and AA in brewers rice, full-fat rice bran (FFRB), defatted rice bran
      (DFRB), peanut meal, sesame meal, rapeseed meal, rapeseed expellers, soybean
      expellers, cassava meal, and bakery meal fed to young growing pigs. Twenty-two
      barrows (initial BW: 14.09 +/- 1.48 kg) were surgically fitted with a T-cannula
      in the distal ileum and randomly allotted to a replicated 11 * 4 incomplete Latin
      square design with 11 diets and four 7-d periods in each square. Eleven
      experimental diets were prepared and test ingredients were the sole source of CP
      and AA in 10 diets and the eleventh diet was a N-free diet used to measure basal
      ileal endogenous losses of CP and AA. Chromic oxide (0.4%) was included in all
      diets as an indigestible marker and ileal digesta were collected on day 6 and 7
      of each period. Results indicated that the SID of CP and AA was greatest (P <
      0.05) in brewers rice and sesame meal and least (P < 0.05) in cassava meal. The
      SID of indispensable AA was greater (P < 0.05) in sesame meal compared with all
      other ingredients except brewers rice. Full-fat rice bran had greater (P < 0.05)
      SID of Arg, Ile, Leu, Lys, and Met compared with DFRB. The SID of CP and most AA
      was not different among rapeseed meal, rapeseed expellers, and soybean expellers.
      Bakery meal had the least (P < 0.05) SID of most AA compared with all other
      ingredients, with the exception of cassava meal. The concentration of
      standardized ileal digestible CP was greater (P < 0.05) in sesame meal and peanut
      meal (482.32 and 452.44 g/kg DM, respectively) than in all other ingredients.
      Soybean expellers had the greatest (P < 0.05) concentration of standardized ileal
      digestible Lys (22.98 g/kg DM) followed by rapeseed meal (16.11 g/kg DM) and
      rapeseed expellers (16.17 g/kg DM). Cassava meal and bakery meal had the least (P
      < 0.05) concentration of standardized ileal digestible CP and most AA compared
      with the other ingredients. Concentrations of standardized ileal digestible CP
      and AA in brewers rice, FFRB, and DFRB were less (P < 0.05) than in rapeseed
      meal, rapeseed expellers, and soybean expellers. In conclusion, peanut meal and
      sesame meal have greater concentrations of standardized ileal digestible CP and
      most AA, with the exception of Lys, than other ingredients. Rapeseed meal,
      rapeseed expellers, and soybean expellers have the greatest concentrations of
      standardized ileal digestible Lys.

PMID- 29579240
TI  - Lethal and Sublethal Effects of Various Pesticides on Trichogramma achaeae
      (Hymenoptera: Trichogrammatidae).
AB  - Little information is available regarding the lethal and sublethal effects of
      pesticides on Trichogramma achaeae (Nagaraja and Nagarkatti; Hymenoptera:
      Tricogrammatidae) during integrated management of Tuta absoluta (Meyrick;
      Lepidoptera: Gelechiidae), an important pest for tomato production. Twenty-two
      pesticides sprayed on Ephestia kuehniella (Zeller; Lepidoptera: Pyralidae) eggs
      were evaluated on the mortality of adult parasitoids upon contact with the hosts
      24 h after the treatments and their sublethal effects on the parasitoids were
      assessed in laboratory conditions. Tests were carried out with fresh solutions at
      the recommended concentration. According to the International Organisation for
      Biological and Integrated Control (IOBC) standards, chlorpyrifos is harmful to
      the parasitoid; merthiocarb, methomyl, spinosad lambda-cyhalothrin, and
      acrinatrin are moderately harmful; and chlorantraniliprole, lufenuron,
      hexythiazox, cyromazine and Bacillus thuringiensis have no effect on the
      parasitoid. Sulfur is slightly harmful, and azoxystrobin is harmless.
      Chlorpyrifos was the most lethal among these pesticides and killed all females in
      less than 24 h. All other pesticides affected the biological parameters of T.
      achaeae to varying degrees. Regarding the lethal and sublethal effects,
      merthiocarb and spinosad killed all female offspring in less than 24 h; lambda
      cyhalothrin and sulfur reduced the number of parasitized eggs; and acrinatrin,
      deltamethrin and azoxystrobin affected the emergence rate. After that, we can
      recommend the use of chlorantraniliprole and B. thuringiensis to control
      Lepidoptera, cyromazine to control Diptera, pirimicarb to control Homoptera,
      hexythiazox to control mites and azoxystrobin can be used as fungicide in an
      integrated pest management program with mass released of T. achaeae.

PMID- 29579241
TI  - Systematic review: What works to address obesity in nurses?
AB  - Background: There is evidence that the prevalence of overweight and obesity among
      nurses is increasing. As well as the impact on health, the costs associated with
      obesity include workplace injury, lost productivity and sickness absence. Finding
      ways to address obesity in nurses may be a challenge because of the barriers they
      face in leading a healthy lifestyle. Aims: To identify the available evidence for
      interventions to address obesity in nurses. Methods: Databases searched included
      CINAHL, SCOPUS (which encompasses the Cochrane Database of Systematic Reviews),
      PsycINFO, MEDLINE and British Nursing Index. Ancillary searching of the grey
      literature was conducted for case studies of weight management interventions in
      National Health Service (NHS) settings. Inclusion criteria were studies involving
      nurses that reported on interventions addressing health behaviours that
      contribute to obesity and included at least one obesity-related outcome measure.
      Results: Eleven primary studies were found concerning lifestyle interventions for
      nurses. There was no strong evidence for any particular intervention to address
      obesity, although integrating interventions into nurses' daily working lives may
      be important. Case studies from the grey literature showcased a range of
      interventions, but very few studies reported outcomes. Conclusions: The review
      demonstrates that there is insufficient good-quality evidence about successful
      interventions to address obesity in nurses. Evidence does indicate that
      interventions should be designed around the specific barriers nurses may face in
      leading a healthy lifestyle.

PMID- 29579242
TI  - Primary hepatic pregnancy.

PMID- 29579243
TI  - Aortic cross-clamp time and cardiopulmonary bypass time: prognostic implications
      in patients operated on for infective endocarditis.
AB  - OBJECTIVES: Prolonged aortic cross-clamp (XCT) and cardiopulmonary bypass time
      (CPBT) are associated with increased morbidity and mortality following cardiac
      surgery. The aim of this study was to assess the predictors of mortality and
      other severe postoperative complications in patients undergoing surgery for
      infective endocarditis (IE), focusing in particular on the role of prolonged XCT
      and CPBT. METHODS: A retrospective single-centre study was conducted from January
      2000 to January 2017, including all patients undergoing valvular surgery for IE.
      The primary end point was early postoperative mortality. The main secondary end
      point was a composite end point for severe postoperative complications. RESULTS:
      During the study period, 264 patients were included. Early postoperative
      mortality was 14%. Prolonged CPBT [odds ratio (OR) 1.008, 95% confidence
      intervals (CIs) 1.003-1.01; P = 0.009] and increasing age (OR 1.04, 95% CI 1.01
      1.07; P = 0.02) independently predicted mortality, while an inverse association
      was observed for left ventricular ejection fraction (OR 0.93, 95% CI 0.89-0.97; P
      = 0.0007). The best mortality cut-offs were >72 min for XCT and >166 min for
      CPBT. Prolonged CPBT also predicted severe complications, along with age, stroke,
      preoperative mechanical ventilation and reduced left ventricular ejection
      fraction. When XCT was included in the multivariable models instead of CPBT, it
      was associated with both mortality and severe complications. CONCLUSIONS:
      Prolonged XCT and CPBT are associated with mortality and development of severe
      complications after valvular surgery for IE. Further validation of safe limits
      for XCT and CPBT might provide novel insights on how to improve intraoperative
      and postoperative outcomes of patients with IE.

PMID- 29579244
TI  - DNA Damage Response of 4-Chloro-Ortho-Toluidine in Various Rat Tissues.
AB  - The potential of 4-chloro-ortho-toluidine (4-CloT), an aromatic amine substituted
      on the ortho- and para-position of the amine function, to induce DNA damage in
      male Wistar rats was evaluated with the micronucleus test (peripheral blood), Pig
      a (peripheral blood), and comet assay (peripheral blood, liver, urinary bladder,
      jejunum) at several time points. In addition to those markers of DNA damage, ie,
      gene mutation and clastogenicity, standard hematology, including methemoglobin,
      histopathology and immunohistochemistry of gamma-H2AX and Ki-67 in liver,
      jejunum, and urinary bladder were performed. 4-CloT was administered orally over
      28 consecutive days (days 1-28), followed by a 28-day treatment-free (days 29
      56), and a second dosing phase of 3 days (days 57-59). 4-CloT showed some effects
      on the integrity of the DNA as measured by the comet assay in liver and urinary
      bladder but not in peripheral blood or jejunum. However, for liver and urinary
      bladder histopathological changes were observed. An increase in the frequency of
      micronuclei in peripheral blood was seen in parallel to a dose-dependent increase
      of reticulocytes and methemoglobin. Therefore, impact from a compensatory
      erythropoiesis on micronucleation cannot be excluded. Interestingly, no increase
      in the frequency of RETCD59- and RBCCD59- was observed in the Pig-a assay.

PMID- 29579245
TI  - The bHLH transcription factor GmPIB1 facilitates resistance to Phytophthora sojae
      in Glycine max.
AB  - Phytophthora sojae Kaufmann and Gerdemann causes Phytophthora root rot, a
      destructive soybean disease worldwide. A basic helix-loop-helix (bHLH)
      transcription factor is thought to be involved in the response to P. sojae
      infection in soybean, as revealed by RNA sequencing (RNA-seq). However, the
      molecular mechanism underlying this response is currently unclear. Here, we
      explored the function and underlying mechanisms of a bHLH transcription factor in
      soybean, designated GmPIB1 (P. sojae-inducible bHLH transcription factor), during
      host responses to P. sojae. GmPIB1 was significantly induced by P. sojae in the
      resistant soybean cultivar 'L77-1863'. Analysis of transgenic soybean hairy roots
      with elevated or reduced expression of GmPIB1 demonstrated that GmPIB1 enhances
      resistance to P. sojae and reduces reactive oxygen species (ROS) accumulation.
      Quantitative reverse transcription PCR and chromatin immunoprecipitation
      quantitative PCR assays revealed that GmPIB1 binds directly to the promoter of
      GmSPOD1 and represses its expression; this gene encodes a key enzyme in ROS
      production. Moreover, transgenic soybean hairy roots with GmSPOD1 silencing
      through RNA interference exhibited improved resistance to P. sojae and reduced
      ROS generation. These findings suggest that GmPIB1 enhances resistance to P.
      sojae by repressing the expression of GmSPOD1.

PMID- 29579246
TI  - High-sensitivity cardiac troponin and natriuretic peptide with risk of lower
      extremity peripheral artery disease: the Atherosclerosis Risk in Communities
      (ARIC) Study.
AB  - Aims: Cardiac troponin T (cTnT) is suggested as a predictor of amputation in
      patients with peripheral artery disease (PAD). However, cTnT-PAD association has
      not been systematically studied in a large study. This study evaluated the
      association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also
      explored whether natriuretic peptide (NT-proBNP), another representative cardiac
      marker, predicts PAD risk. Methods and results: Among 12 288 middle-aged adults,
      the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations
      with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss
      considered as critical limb ischaemia (CLI)]) were quantified with multivariable
      Cox regression models. The risk discrimination was assessed by c-statistic.
      During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases).
      In demographically adjusted models, the highest category of hs-cTnT (>=14 vs. <3
      ng/L) and NT-proBNP (>=258.3 vs. <51.5 pg/mL) showed ~8- and 10-20-fold higher
      risk of PAD and CLI, respectively. Even after adjusting for potential confounders
      and each other, hazard ratios were greater for CLI than for PAD (7.74 95%
      confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs.
      reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the
      highest vs. reference NT-proBNP category). The addition of these cardiac markers
      improved c-statistics for CLI. Conclusion: High-sensitivity cTnT and NT-proBNP
      were independently associated with incident PAD, particularly its severe form,
      CLI. Although future studies are warranted to investigate pathophysiological
      mechanisms behind these associations, our study suggests the usefulness of
      cardiac markers to identify individuals at high risk of CLI.

PMID- 29579247
TI  - Reduced fecundity in HIV-positive women.
AB  - STUDY QUESTION: Is HIV associated with increased time to pregnancy (TTP)? SUMMARY
      ANSWER: HIV-positive women who discontinue a contraceptive method to become
      pregnant have increased TTP, particularly among those who likely do not know
      their status. WHAT IS KNOWN ALREADY: HIV-positive women have fewer children on
      average than their HIV-negative counterparts due to both behavioral and
      biological factors. There is a need to better describe and quantify fecundity
      patterns associated with HIV in the general population. STUDY DESIGN, SIZE,
      DURATION: This cross-sectional study was based on data from 12 Demographic and
      Health Surveys (DHSs) conducted between 2003 and 2013 in 11 African countries.
      All studies collected dried blood spot samples for HIV testing and included a
      retrospective calendar module that recorded women's monthly reproductive status
      in the 5 years preceding the survey. TTP was measured among 3181 women
      discontinuing a contraceptive method within 2 years of the survey in order to
      become pregnant. PARTICIPANTS/MATERIALS, SETTING, METHODS: We use Cox
      proportional hazard models for discrete survival data to model TTP and estimate
      fecundability odds ratios (FOR) and 95% CIs for the 12-month period following
      contraceptive discontinuation. In addition to employing a binary measure of HIV
      status, we also develop an additional explanatory measure that combines HIV
      status with information on whether respondents had ever been tested for HIV and
      received their results (which proxies for knowledge of HIV status) to reduce the
      threat of confounding from behavioral changes following an HIV diagnosis. MAIN
      RESULTS AND THE ROLE OF CHANCE: In our sample, 10.3% of women were HIV-positive,
      and a little more than half (51.8%) of women received test results and likely
      knew their status. Over a 12-month observation period, HIV-positive women had a
      25% average reduction in fecundity compared to HIV-negative women [adjusted FOR
      (aFOR) = 0.75 (0.62-0.92)] after adjusting for confounders. The 12-month
      fecundity patterns differed by women's likely knowledge of their status such that
      results were primarily driven by HIV-positive women who likely did not know their
      status. Moreover, reductions in fecundity attributable to HIV were not uniform
      over time. Among women who were still trying for pregnancy after 3 unsuccessful
      months, HIV-positive women had half the odds of becoming pregnant compared to HIV
      negative women [aFOR = 0.50 (0.35-0.71)]. Conversely, there were no significant
      differences in FORs between HIV-negative and HIV-positive women in the first 3
      months. LIMITATIONS REASONS FOR CAUTION: Because dried blood spot samples for HIV
      testing were collected at the time of the survey but reproductive calendar data
      were collected retrospectively, it is possible that we introduced
      misclassification bias, as we have no knowledge if the acquisition of HIV
      occurred before or after pregnancy attempt. WIDER IMPLICATIONS OF THE FINDINGS:
      As life expectancy and quality health status improve due to earlier initiation of
      antiretroviral (ARV) treatment in HIV-positive women, there has been growing
      awareness that services should also address the fertility desires of HIV-positive
      women who want children. These findings indicate that if a pregnancy does not
      occur after 3 months of attempting pregnancy, HIV-positive women and HIV
      discordant couples should request access to HIV and reproductive pre-pregnancy
      counseling and health assessments. STUDY FUNDING/COMPETING INTEREST(S): A.G. was
      supported by the National Institutes of Health (contract T32-HD007275) during the
      study. During the conceptualization, data collection and analysis time frame,
      S.vdP. was supported by WHO/RHR/HRP Special Program in Reproductive Health and
      Research, Geneva, Switzerland, and HRP (the UNDP/UNFPA/UNICEF/WHO/World Bank
      Special Programme of Research, Development and Research Training in Human
      Reproduction). The authors have no conflicts of interest to declare.

PMID- 29579248
TI  - Leber's hereditary optic neuropathy (LHON)-associated ND5 12338T > C mutation
      altered the assembly and function of complex I, apoptosis and mitophagy.
AB  - Mutations in mitochondrial DNA (mtDNA) have been associated with Leber's
      hereditary optic neuropathy (LHON) and their pathophysiology remains poorly
      understood. In this study, we demonstrated that a missense mutation (m.12338T>C,
      p.1M>T) in the ND5 gene contributed to the pathogenesis of LHON. The m.12338T>C
      mutation affected the first methionine (Met1) with a threonine and shortened two
      amino acids of ND5. We therefore hypothesized that the mutated ND5 perturbed the
      structure and function of complex I. Using the cybrid cell models, generated by
      fusing mtDNA-less (rho degrees ) cells with enucleated cells from LHON patients
      carrying the m.12338T>C mutation and a control subject belonging to the same
      mtDNA haplogroup, we demonstrated that the m.12338T>C mutation caused the
      reduction of ND5 polypeptide, perturbed assemble and activity of complex I.
      Furthermore, the m.12338T>C mutation caused respiratory deficiency, diminished
      mitochondrial adenosine triphosphate levels and membrane potential and increased
      the production of reactive oxygen species. The m.12338T>C mutation promoted
      apoptosis, evidenced by elevated release of cytochrome c into cytosol and
      increased levels of apoptosis-activated proteins: caspases 9, 3, 7 and Poly ADP
      ribose polymerase in the cybrids carrying the m.12338T>C mutation, as compared
      with control cybrids. Moreover, we also document the involvement of m.12338T>C
      mutation in decreased mitophagy, as showed by reduced levels of autophagy protein
      light chain 3 and accumulation of autophagic substrate p62 in the in mutant
      cybrids as compared with control cybrids. These data demonstrated the direct link
      between mitochondrial dysfunction caused by complex I mutation and apoptosis or
      mitophagy. Our findings may provide new insights into the pathophysiology of
      LHON.

PMID- 29579249
TI  - A misleading diagnosis of granulomatosis with polyangiitis disguising Whipple's
      disease.

PMID- 29579250
TI  - Reduction in Cigarettes Per Day Prospectively Predicts Making a Quit Attempt: A
      Fine-Grained Secondary Analysis of a Natural History Study.
AB  - Introduction: Reducing cigarettes per day (CPD) aided by medication increases
      quit attempts (QA) among smokers not trying to quit. If this is due to reducing
      CPD per se, then a greater reduction should predict making a QA. Methods: In this
      secondary analysis, 132 smokers completed nightly calls to report CPD, intention
      to quit tomorrow, and QAs over 12 weeks. We provided no treatment. We identified
      episodes of reduction and tested whether a) percent reduction in CPD, b) absolute
      CPD reduced, c) duration of reduction, or d) CPD on the final day, predicted a QA
      immediately after a reduction episode. We tested this separately among reduction
      episodes that began with and without an intention to quit. Results: Among the
      1,179 episodes that began without intention to quit, all four measures of
      reduction predicted making a QA. Greater percent reduction, longer duration, and
      fewer CPD on the final day were retained in a multivariate model (all p<.05).
      Among the 85 episodes that began with intention to quit, greater percent
      reduction and greater absolute reduction predicted making a QA. Only mean percent
      reduction was retained in a multivariate model (p<.001). Conclusions: Our results
      replicate and extend earlier studies by using fine-grain analyses and examining
      immediately proximal QAs in a sample of self-quitters. Findings suggest that
      reducing CPD per se increases the probability of a QA among smokers without
      intention to quit in a dose-related manner. Whether this is the case among
      smokers who intend to quit remains unclear. Implications: Reducing CPD appears to
      be an effective strategy to increase the probability of making a QA for the
      majority of smokers who do not intend to quit in the near future. However, our
      findings are mixed regarding the effectiveness of reducing among smokers who
      intend to quit. Clinical interventions and polices that promote reducing CPD are
      likely to be an effective way to increase QAs. Reduction may be especially
      helpful for smokers who have not responded to traditional advice to stop
      abruptly.

PMID- 29579251
TI  - Incidence of Healthcare-Associated Influenza-Like Illness After a Primary Care
      Encounter Among Young Children.
AB  - Background: Despite potential respiratory virus transmission in pediatric
      clinics, little is known about the risk of healthcare-associated viral infections
      attributable to outpatient encounters. We evaluated whether exposure to a
      pediatric clinic visit was associated with subsequent influenza-like illness
      (ILI). Methods: Using electronic health record data, we conducted a retrospective
      cohort study of all children aged <6 years who presented to a provider in a 29
      clinic pediatric primary care network for a non-ILI-related encounter over 2
      respiratory virus seasons (September 1, 2012, to April 30, 2014). We defined a
      risk period for potential healthcare-associated (HA) ILI of 1 to 8 days after a
      non-ILI clinic visit and identified all cases of ILI to compare the incidences of
      ILI visits 1 to 8 days after a non-ILI encounter and those of visits >8 days
      after a non-ILI encounter. Results: Among 149987 children <6 years of age (mean
      age, 2.5 years) with >=1 non-ILI visit during the study period, 531928 total
      encounters and 13951 (2.9%) ILI encounters were identified; 1941 (13.9%) occurred
      within the HA-ILI risk window. The incidence rate ratios (IRRs) for ILI 1 to 8
      days after compared with ILI >8 days after a non-ILI visit during season 1 were
      1.36 (95% confidence interval, 1.22-1.52) among children >=2 years of age and
      1.01 (95% confidence interval, 0.93-1.09) among children <2 years of age.
      Estimates remained consistent during season 2 and with a risk window of 3, 4, or
      9 days. Conclusions: Pediatric clinic visits during a respiratory virus season
      were significantly associated with an increased incidence of subsequent ILI among
      children aged 2 to 6 years but not among those aged <2 years. These findings
      support the hypothesis that respiratory virus transmission in a pediatric clinic
      can result in HA ILI in young children.

PMID- 29579252
TI  - Epigenetic modulation as a therapy in systemic sclerosis.
AB  - SSc is an autoimmune idiopathic disease in which there is an inflammatory
      component driving fibrosis. The chief cell involved is the myofibroblast, which
      when activated secretes copious amounts of extracellular matrix that forms
      deposits, leading to stiffness and fibrosis. The fibrosis is most prevalent in
      the skin and lungs. In recent years epigenetic modifications have been uncovered
      that positively and negatively regulate the genesis of the myofibroblasts and
      that can be activated and regulated by a variety of cytokines and hormones. The
      epigenetic contribution to these cells and to SSc is only now really coming to
      light, and this opens up a new therapeutic target for the disease for which many
      epigenetic drugs, such as miRNA replacements, are beginning to be developed. This
      review will examine the epigenetic regulators in the disease and possible
      targeting of these.

PMID- 29579254
TI  - The Tendril Plot-a novel visual summary of the incidence, significance and
      temporal aspects of adverse events in clinical trials.
AB  - Background: In contrast to efficacy, safety hypotheses of clinical trials are not
      always pre-specified, and therefore, the safety interpretation work of a trial
      tends to be more exploratory, often reactive, and the analysis more statistically
      and graphically challenging. Methods: We introduce a new means of visualizing the
      adverse event data across an entire clinical trial. Results: The approach
      overcomes some of the current limitations of adverse event analysis and
      streamlines the way safety data can be explored, interpreted and analyzed. Using
      a phase II study, we describe and exemplify how the tendril plot effectively
      summarizes the time-resolved safety profile of two treatment arms in a single
      plot and how that can provide scientists with a trial safety overview that can
      support medical decision making. Conclusion: To our knowledge, the tendril plot
      is the only way to graphically show important treatment differences with
      preserved temporal information, across an entire clinical trial, in a single
      view.

PMID- 29579253
TI  - Diverse Evolutionary Origins and Mechanisms of Lens Regeneration.
AB  - In this review, we compare and contrast the three different forms of vertebrate
      lens regeneration: Wolffian lens regeneration, cornea-lens regeneration, and lens
      regeneration from lens epithelial cells. An examination of the diverse cellular
      origins of these lenses, their unique phylogenetic distribution, and the
      underlying molecular mechanisms, suggests that these different forms of lens
      regeneration evolved independently and utilize neither conserved nor convergent
      mechanisms to regulate these processes.

PMID- 29579255
TI  - Performance of In Silico Models for Mutagenicity Prediction of Food Contact
      Materials.
AB  - In silico methodologies, such as (quantitative) structure-activity relationships
      ([Q]SARs), are available to predict a wide variety of toxicological properties
      and biological activities for structurally diverse substances. To obtain insights
      in the scientific value of these predictions, the capacity of the prediction
      models to generate (sufficiently) reliable results for a particular type of
      compounds needs to be evaluated. In the current study, performance parameters to
      predict the endpoint "bacterial mutagenicity" were calculated for a battery of
      common (Q)SAR tools, namely Toxtree, Derek Nexus, VEGA Consensus, and Sarah
      Nexus. Printed paper and board food contact material (FCM) constituents were
      chosen as study substances because many of these lack experimental data, making
      them an interesting group for in silico screening. Accuracy, sensitivity,
      specificity, positive predictivity, negative predictivity, and Matthews
      correlation coefficient for the individual models and for the combination of VEGA
      Consensus and Sarah Nexus were determined and compared. Our results demonstrate
      that performance varies among the four models, but can be increased by applying a
      combination strategy. Furthermore, the importance of the applicability domain is
      illustrated. Limited performance to predict the mutagenic potential of substances
      that are new to the model (ie, not included in the training set) is reported. In
      this context, the generally poor sensitivity for these new substances is also
      addressed.

PMID- 29579256
TI  - Characterization of the Neutralizing Antibody Response in a Case of Genetically
      Linked HIV Superinfection.
AB  - This report describes the identification of a genetically confirmed linked
      heterosexual human immunodeficiency virus (HIV) superinfection (HIV-SI) in a
      woman with chronic HIV infection who acquired a second strain of the virus from
      her husband. Serum neutralizing antibody (NAb) responses against their homologous
      and heterologous viruses, including the superinfecting strain, in the woman and
      her husband were examined before and after onset of HIV-SI. The woman displayed a
      moderately potent and broad anti-HIV NAb response prior to superinfection but did
      not possess NAb activity against the superinfecting strain. This case highlights
      the unique potential of linked HIV-SI studies to examine natural protection from
      HIV infection.

PMID- 29579257
TI  - Pyloroplasty may reduce weight loss 1 year after esophagectomy.
AB  - Weight loss after esophagectomy is common and is associated with unfavorable
      prognosis. However, the clinical features and surgical methods that influence
      postesophagectomy weight loss are not well characterized. This study aims to
      determine those features (especially the surgical methods) that may affect
      postoperative weight loss. We reviewed 221 esophageal cancer patients who had
      undergone esophagectomy at Kumamoto University Hospital (Kumamoto, Japan) between
      November 2012 and June 2015. Among these, we recruited 106 patients who had
      undergone transthoracic esophagectomy with gastric conduit reconstruction, had no
      cancer recurrence within 1 year, and no missing follow-up data. We tabulated the
      body weight changes and risk factors associated with weight loss exceeding 10% at
      1-year postesophagectomy. The mean body weights at baseline and 1-year
      postsurgery were 60.3 kg (standard error (SE): 0.91) and 52.6 (SE: 0.91),
      respectively. One year postsurgery, the body weights had changed as follows:
      mean: -12.2%; median: -12.9%; standard deviation: 9.06; range: -36.1-18.56%;
      interquartile range: -10.5 to -14.0%. In the multivariate logistic regression
      analysis, the absence of pyloroplasty was the sole risk factor for more than 10%
      weight loss (OR: 3.22; 95% CI: 1.08-11.9; P = 0.036). Our data suggest that
      pyloroplasty with esophagectomy can overcome the post-surgical weight loss.

PMID- 29579258
TI  - DNA silencing by prokaryotic Argonaute proteins adds a new layer of defense
      against invading nucleic acids.
AB  - Argonaute (Ago) proteins are encoded in all three domains of life and are
      responsible for the regulation of intracellular nucleic acid levels. Whereas some
      Ago variants are able to cleave target nucleic acids by their endonucleolytic
      activity, others only bind to their target nucleic acids while target cleavage is
      mediated by other effector proteins. Although all Ago proteins show a high degree
      of overall structural homology, the nature of the nucleic acid binding partners
      differs significantly. Recent structural and functional data have provided
      intriguing new insights into the mechanisms of archaeal and bacterial Ago
      variants demonstrating the mechanistic diversity within the prokaryotic Ago
      family with astonishing differences in nucleic acid selection and nuclease
      specificity. In this review, we provide an overview of the structural
      organisation of archaeal Ago variants and discuss the current understanding of
      their biological functions that differ significantly from their eukaryotic
      counterparts.

PMID- 29579260
TI  - PAH exposure-associated lung cancer: an updated meta-analysis.
AB  - Background: Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has
      been shown to be associated with lung cancer in various epidemiological studies
      in industries such as aluminium reduction/smelting, coal gasification, coke
      production, iron/steel foundries, coal/coke and related products and
      carbon/graphite electrodes production. Aims: To update data on the association
      between PAH exposure and morbidity and mortality due to lung cancer among workers
      in different occupations, including smoking data. Methods: A comprehensive
      literature search was conducted to retrieve relevant papers for meta-analysis.
      Cohort studies with standardized mortality ratios or standardized incidence
      ratios and calculated overall risk ratio with their corresponding 95% confidence
      intervals (CIs) were included in the analysis. Chi-square test for heterogeneity
      was used to evaluate the consistency of findings between the studies. Results: A
      significant risk of lung cancer was observed among the coal/coke and related
      product industry 1.55 (95% CI 1.01-2.37) and the iron/steel foundry industry 1.52
      (95% CI 1.05-2.20). There was a wide variation in smoking habits and PAHs
      exposure among studies. Conclusions: Coal/coke industry and iron/steel industry
      workers showed a higher risk of lung cancer compared with other occupations
      exposed to PAHs. The confounding effects of smoking and individual exposure
      levels of PAH should be taken into account.

PMID- 29579261
TI  - NeuroForm Atlas Stent-Assisted Coiling: Preliminary Results.
AB  - BACKGROUND: Stent-assisted coiling (SAC) is increasingly being performed as
      intervention for wide-neck intracranial aneurysms. The NeuroForm Atlas Stent (CE
      marked; Stryker, Kalamazoo, Michigan) is relatively new. OBJECTIVE: To evaluate
      the effectiveness and safety of NeuroForm Atlas SAC for intracranial aneurysms in
      the first such study. METHODS:  We retrospectively analyzed data from all
      patients treated with the NeuroForm Atlas SAC of an intracranial aneurysm, both
      ruptured and unruptured, between June 2015 and December 2016. Primary end-points
      were favorable clinical outcomes (modified Rankin scale score 0-2) and successful
      aneurysm occlusion (Raymond-Roy class I/II), both at 6-mo follow-up. Secondary
      end-points were the occurrence of intervention-related complications leading to
      permanent neurological deficit, the occurrence of intervention-related stroke and
      neurological death, immediate aneurysm occlusion, rupture (or rerupture) of the
      aneurysm, and recanalization. RESULTS: Twenty-seven consecutive patients, 10 with
      ruptured saccular wide-neck aneurysms, were treated with NeuroForm Atlas SAC. At
      6-mo follow-up, 18/26 (69.2%) survivors had successful aneurysm occlusion and
      22/26 (84.6%) had favorable clinical outcome. One patient had died of a cause
      unrelated to treatment. No intervention-related complications leading to
      permanent neurological deficit occurred. However, intraprocedural thromboembolic
      complications occurred in 4/27 patients (14.8%), and ischemic stroke related to
      treatment occurred in 4/26 (15.4%). No hemorrhagic complications were observed.
      CONCLUSION: NeuroForm Atlas SAC is a feasible way to treat ruptured and
      unruptured wide-neck aneurysms that are not amenable to conventional coiling or
      clipping. Aneurysm occlusion and favorable clinical outcome are consistent with
      previously reported rates for SAC of wide-neck aneurysms with other devices.

PMID- 29579262
TI  - Acute kidney injury in critically ill patients with solid tumours.
AB  - Background: Patients with solid tumours are at risk for acute kidney injury
      (AKI), however, epidemiological data are limited. Methods: We conducted a study
      that included patients with solid tumours admitted to a single-centre intensive
      care unit (ICU) from January 2011 to December 2015. We analysed factors
      associated with the occurence of AKI, ICU and Day-90 mortality. Results: Two
      hundred and four patients were included. The incidence of AKI was 59%, chiefly
      related to sepsis (80%), hypovolaemia (40%) and outflow tract obstruction (17%).
      Renal replacement therapy was implemented in 12% of the patients, with a hospital
      mortality of 39%. Independent predictors of AKI were: Simplified Acute
      Physiological Score II (SAPS II) [odds ratio (OR) 1.05; 95% confidence interval
      (95% CI) 1.02-1.07; P < 0.001], abdominal or pelvic cancer (OR 2.84; 95% CI 1.35
      5.97; P = 0.006), nephrotoxic chemotherapy within the previous 3 months (OR 3.84;
      95% CI 1.67-8.84; P = 0.002) and sepsis (OR 2.74; 95% CI 1.30-5.77; P = 0.008).
      Renal recovery at Day 90 was inversely related to AKI severity. ICU, hospital and
      Day-90 mortality were 15, 29 and 37%, respectively. Factors independently
      associated with ICU mortality were: total serum protein (OR per 10 g/L, 0.44; 95%
      CI 0.23-0.86; P = 0.02) and SAPS II (OR 1.04; 95% CI 1.01-1.07; P = 0.02), while
      Day-90 mortality was associated with performance status 3-4 (OR 6.59; 95% CI 2.42
      18; P < 0.001) and total serum protein (OR 0.60; 95% CI 0.38-0.94; P = 0.02).
      Conclusions: AKI in patients with solid tumours was frequent and renal recovery
      gradually decreased in proportion to AKI severity. However, AKI was not
      independently associated with a higher short-term mortality.

PMID- 29579259
TI  - High Rates of Prescribing Antimicrobials for Prophylaxis in Children and
      Neonates: Results From the Antibiotic Resistance and Prescribing in European
      Children Point Prevalence Survey.
AB  - Background: This study was conducted to assess the variation in prescription
      practices for systemic antimicrobial agents used for prophylaxis among pediatric
      patients hospitalized in 41 countries worldwide. Methods: Using the standardized
      Antibiotic Resistance and Prescribing in European Children Point Prevalence
      Survey protocol, a cross-sectional point-prevalence survey was conducted at 226
      pediatric hospitals in 41 countries from October 1 to November 30, 2012. Results:
      Overall, 17693 pediatric patients were surveyed and 36.7% of them received
      antibiotics (n = 6499). Of 6818 inpatient children, 2242 (32.9%) received at
      least 1 antimicrobial for prophylactic use. Of 11899 prescriptions for
      antimicrobials, 3400 (28.6%) were provided for prophylactic use. Prophylaxis for
      medical diseases was the indication in 73.4% of cases (2495 of 3400), whereas
      26.6% of prescriptions were for surgical diseases (905 of 3400). In approximately
      half the cases (48.7% [1656 of 3400]), a combination of 2 or more antimicrobials
      was prescribed. The use of broad-spectrum antibiotics (BSAs), which included
      tetracyclines, macrolides, lincosamides, and sulfonamides/trimethoprim, was high
      (51.8% [1761 of 3400]). Broad-spectrum antibiotic use for medical prophylaxis was
      more common in Asia (risk ratio [RR], 1.322; 95% confidence interval [CI], 1.202
      1.653) and more restricted in Australia (RR, 0.619; 95% CI, 0.521-0.736).
      Prescription of BSA for surgical prophylaxis also varied according to United
      Nations region. Finally, a high percentage of surgical patients (79.7% [721 of
      905]) received their prophylaxis for longer than 1 day. Conclusions: A high
      proportion of hospitalized children received prophylactic BSAs. This represents a
      clear target for quality improvement. Collectively speaking, it is critical to
      reduce total prophylactic prescribing, BSA use, and prolonged prescription.

PMID- 29579263
TI  - Etiology of Placental Plasmodium falciparum Malaria in African Women.
AB  - Plasmodium falciparum parasites causing placental malaria express the VAR2CSA
      type of the clonally variant antigen family erythrocyte membrane protein 1
      (PfEMP1). This enables evasion of preexisting immunity and results in placental
      accumulation of infected erythrocytes. We present data on seasonal variation in
      levels of VAR2CSA-specific immunoglobulin G (IgG) and IgG specific for a
      placental malaria-unrelated PfEMP1 protein among Ghanaian women at their first
      antenatal visit. Our results indicate that placental malaria does not require
      recent exposure to infected mosquitoes, in contrast to malaria in general. This
      has implications for the impact of insecticide-treated bed nets on placental
      malaria incidence and for antenatal care in woman with preexisting immunity.

PMID- 29579264
TI  - Potassium: an ion with dangerous airs and graces.
AB  - Take home figureFactors promoting hypokalaemia and hyperkalaemia. CHF, chronic
      heart failure; CKD, chronic kidney disease.

PMID- 29579265
TI  - Imaging of the sacroiliac joints is important for diagnosing early axial
      spondyloarthritis but not all-decisive.
AB  - Objectives: To evaluate the contribution of the results of sacroiliac imaging to
      diagnosis and to the level of confidence in diagnosis in patients presenting with
      chronic back pain (CBP) and suspected of having axial spondyloarthritis (axSpA).
      Methods. Data from 513 patients from the SPondyloArthritisCaughtEarly cohort with
      CBP (?3 months, ?2 years, onset <45 years) were analysed after full diagnostic
      work-up. Rheumatologists were asked not only to provide a diagnosis before and
      after the imaging results had been provided to them, but also to provide the
      level of confidence of this diagnosis on an 11-point numerical scale. Results.
      Before imaging, 317/513 patients were diagnosed with axSpA. Of these patients,
      178/317 (56%) did not have signs of sacroiliitis on either MRI or radiography,
      which led to the rheumatologist refuting the initial diagnosis of axSpA in 81/178
      (46%) patients. Of the 196/513 patients without axSpA before imaging, 35/196
      (18%) had signs of sacroiliitis on imaging. Subsequently, 28/35 (80%) patients
      were diagnosed with axSpA. Overall, imaging was incongruent with the diagnosis
      before imaging in 213 patients. This led to a change in diagnosis in 109/213
      (51%), which corresponds to 21% (109/513) of all patients in the cohort. In
      general, diagnostic confidence increased by having imaging results available
      (from 6.2 to 7.4, P < 0.001). Conclusion: In patients with CBP suspected of
      having axSpA, sacroiliac imaging adds to the confidence in the final diagnosis.
      However, the number of changes in diagnosis suggests that imaging is important
      but not all-decisive in early axSpA diagnosis.

PMID- 29579266
TI  - Time-Dependent Postmortem Redistribution of Opioids in Blood and Alternative
      Matrices.
AB  - Forensic postmortem case interpretation can be challenging, in particular due to
      postmortem redistribution (PMR) phenomena. Recent studies have shown that
      computed tomography (CT)-guided collection of biopsy samples using a robotic arm
      (virtobot) provides a valuable tool for systematic studies on time-dependent PMR.
      Utilizing this strategy, several cases involving opioid use such as methadone,
      fentanyl, tramadol, codeine, oxycodone and hydrocodone were evaluated for time
      dependent concentration changes and potential redistribution mechanisms. Upon
      admission to the institute (t1), blood (femoral and right ventricle heart blood)
      and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose
      tissue) were collected utilizing CT-guided biopsy. Approximately 24 h later (t2;
      mean 28 +/- 15 h), during the autopsy, samples from the same body regions were
      collected manually and in addition brain tissue, gastric content, urine and left
      ventricle heart blood. Analysis was conducted with liquid chromatography tandem
      mass spectrometry. Significant time-dependent methadone concentration increases
      in femoral blood (pB) indicate the occurrence of PMR, however, ultimately not
      relevant for forensic interpretation. The main metabolite of methadone, 2
      ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), showed a less significant
      trend for PMR. Redistribution by passive diffusion along the muscle-to-pB
      concentration gradient seems likely for methadone, but not for EDDP. Results for
      fentanyl suggest extensive PMR. Other opioids such as tramadol, codeine,
      hydrocodone and oxycodone showed no consistent trend for significant PMR.
      Overall, CT-guided biopsy sampling proved to be a valuable tool for the
      investigation of PMR mechanisms.

PMID- 29579268
TI  - An Overview of the Use of Bromelain-Based Enzymatic Debridement (Nexobrid(r)) in
      Deep Partial and Full Thickness Burns: Appraising the Evidence.
AB  - Recent introduction of rapid bromelain-based enzymatic debridement has been
      increasingly popular in its use in nonsurgical debridement in deep partial and
      full thickness burns. We designed this study to evaluate the evidence suggested
      by current studies on the perceived benefits of using Nexobrid(r) compared with
      traditional surgical standard of care in burns wound debridement. A comprehensive
      search on electronic databases Pubmed, Embase, and Web of Science was done to
      identify studies published between 1986 and 2017 involving the use of Nexobrid(r)
      in deep partial and full thickness burns. Studies were evaluated for proposed
      benefits and categorized under supporting evidence, contradicting evidence, and
      anecdotal opinions. Seven well-designed prospective studies met the inclusion
      comprising four randomized controlled trials. Six proposed benefits associated
      with the use of Nexobrid(r) were extracted including reduced time to complete
      debridement, need for surgery, area of burns excised, need for autograft, time to
      wound closure, and improved scar quality. Most proposed benefits have strong
      supporting evidences with minimal anecdotal opinions from controlled trials
      except the proposed improvement in scar quality and reduced time to wound healing
      that had at least three refuting evidence and one anecdotal evidence. Incidence
      of pain was also evaluated and was mainly anecdotal lacking formal objective
      assessment or cohort study. Despite the lack of literatures available, the
      benefits of Nexobrid(r) are evident in published randomized and single arm
      studies. Large number of studies is needed to aid further evaluating the proposed
      benefits of Nexobrid(r).

PMID- 29579267
TI  - Myosin XI-K is involved in root organogenesis, polar auxin transport, and cell
      division.
AB  - The interplay between myosin- and auxin-mediated processes was investigated by
      following root development in the triple myosin knockout mutant xi-k xi-1 xi-2
      (3KO). It was found that the 3KO plants generated significantly more lateral and
      adventitious roots than the wild-type plants or the rescued plant line expressing
      functional myosin XI-K:yellow fluorescent protein (YFP; 3KOR). Using the auxin
      dependent reporter DR5:venus, a significant change in the auxin gradient toward
      the root tip was found in 3KO plants, which correlated with the loss of polar
      localization of the auxin transporter PIN1 in the stele and with the increased
      number of stele cells with oblique cell walls. Interestingly, myosin XI-K:YFP was
      localized to the cell division apparatus in the root and shoot meristems. In
      anaphase and early telophase, XI-K:YFP was concentrated in the midzone and the
      forming cell plate. In late telophase, XI-K:YFP formed a ring that overlapped
      with the growing phragmoplast. Myosin receptors MyoB1 and MyoB2 that are highly
      expressed throughout the plant were undetectable in dividing cells, suggesting
      that the myosin function in cell division relies on distinct adaptor proteins.
      These results suggest that myosin XIs are involved in orchestrating root
      organogenesis via effects on polar distribution of auxin responses and on cell
      division.

PMID- 29579269
TI  - Prediction of digestible and metabolizable energy of corn distillers dried grains
      with solubles for growing pigs using in vitro digestible nutrients.
AB  - The objective of this study was to develop prediction equations (EQS) that
      estimate DE and ME content of corn distillers dried grains with solubles (DDGS)
      using digestible (DIG) nutrients from in vitro or in vivo assays. Chemical
      composition data from 12 sources of corn DDGS were obtained using laboratory
      chemical analysis (LCA) and near infrared spectroscopy (NIRS). In vitro DM
      disappearance (IVDMD) from gastric and small intestine hydrolysis (IVDMDh), large
      intestine fermentation (IVDMDf), and total tract digestion (IVDMDt) were also
      determined along with in vivo apparent total tract digestibility (ATTD) of DM,
      CP, ether extract (EE), NDF, and ADF, and energy values (GE, DE, and ME).
      Correlation analysis was used to compare chemical composition from LCA with NIRS,
      and a stepwise selection of variables was performed using linear regression to
      establish DE and ME prediction EQS. Composition determined by NIRS did not
      correlate with values from LCA. Consequently, significance and R2 were poorer
      when using NIRS data as inputs to predict DE (P = 0.11; R2 = 0.23) and ME (P =
      0.11; R2 = 0.24). However, when using LCA data, DE (P = 0.04; R2 = 0.35) and ME
      (P = 0.04; R2 = 0.52) estimates of corn DDGS obtained from prediction EQS had
      significant P values, but low R2. Better prediction of DE (P < 0.01; R2 = 0.83)
      and ME (P < 0.01; R2 = 0.76) was observed when using in vivo DIG nutrients as
      inputs (DM basis) for DE, kcal/kg = 854.5 + (3.6 * DIG DM, g/kg) + (3.7 * DIG EE,
      g/kg) + (2.0 * DIG NDF, g/kg) and ME, kcal/kg = 704.5 + (3.3 * DIG DM, g/kg) +
      (4.8 * DIG EE, g/kg) + (2.6 * DIG NDF, g/kg). In vitro DIG DM, but not in vitro
      DIG NDF, was selected for use in EQS (7) DE, kcal/kg = 6,383.6 - (42.5 * in vitro
      DIG DM, g/kg) + (35.4 * DIG EE, g/kg) and (8) ME, kcal/kg = 6,635.1 - (49.8 * in
      vitro DIG DM, g/kg) + (41.3 * DIG EE, g/kg), but the significance and accuracy
      for both DE (P = 0.07; R2 = 0.45) and ME (P = 0.05; R2 = 0.49) predictions was
      less using in vitro DIG nutrient values than using in vivo DIG nutrient values.
      If chemical composition was used to replace in vivo EE, along with in vitro DIG
      NDF and DM, the prediction EQS only used the concentration of ADF and EE as
      predictors instead of in vitro DIG NDF and DM. In conclusion, in vivo DIG NDF,
      DM, and EE are the best predictors for DE and ME content of corn DDGS for swine.
      Using NIRS to determine chemical composition, in vitro DIG NDF, and in vitro DIG
      DM did not result in accurate predictions of DE and ME.

PMID- 29579270
TI  - Analysis of segregation patterns of quadrivalent structures and the effect on
      genome stability during meiosis in reciprocal translocation carriers.
AB  - STUDY QUESTION: Do specific factors affect the segregation patterns of a
      quadrivalent structure and can the quadrivalent affect genome stability during
      meiosis? SUMMARY ANSWER: Meiotic segregation patterns can be affected by the
      carrier's gender and age, location of breakpoints and chromosome type, and the
      quadrivalent structure can increase genome instability during meiosis. WHAT IS
      KNOWN ALREADY: Carriers of reciprocal translocations have an increased genetic
      reproductive risk owing to the complex segregation patterns of a quadrivalent
      structure. However, the results of previous studies on the factors that affect
      segregation patterns seem to be contradictory, and the effect of a quadrivalent
      on genome stability during meiosis is unknown. STUDY DESIGN, SIZE, DURATION: We
      designed a retrospective study to analyze the segregation patterns of 24
      chromosomes from reciprocal translocation and non-translocation patients. Data
      for 356 reciprocal translocation carriers and 53 patients with the risk to
      transmit monogenic inherited disorders (RTMIDs) undergoing PGD-single nucleotide
      polymorphism array analysis were collected. The study was performed between March
      2014 and July 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Segregation
      patterns of a quadrivalent in 1842 blastocysts from 466 assisted reproduction
      cycles of reciprocal translocation carriers were analyzed according to the
      location of chromosome breakpoints, the carrier's gender and age, and chromosome
      type. In addition, to analyze the effect of quadrivalent structure on genome
      stability, segregation products of chromosomes which are not involved in the
      translocation from translocation carriers were compared with those of 23 pairs of
      chromosomes in 318 blastocysts from 72 assisted reproduction cycles of patients
      with RTMIDs. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of adjacent-2
      products with severe asymmetric quadrivalent was significantly higher than those
      with mild asymmetric quadrivalent (P = 0.020) while, in contrast, the incidence
      of 4:0/others was lower (P = 0.030). The frequencies of adjacent-1, adjacent-2
      and 3:1 products differed between male and female carriers (P < 0.001, P = 0.015
      and P = 0.001, respectively), and also for adjacent-1 and 4:0/others products in
      young versus older carriers (P = 0.04 and P = 0.002, respectively). In addition,
      adjacent-1 products of a quadrivalent with an acrocentric chromosome were
      significantly higher than those of a quadrivalent without an acrocentric
      chromosome (P = 0.001). Moreover, a quadrivalent could significantly increase the
      frequencies of abnormal chromosomes compared to patients with RTMIDs (P = 0.048,
      odds ratio (OR) = 1.43, 95% CI = 1.01-2.43), especially for the male carriers (P
      = 0.018, OR = 1.58, 95% CI = 1.08-2.25). In contrast, for older carriers, no
      difference was found in both aneuploidy and segmental anomalies compared to
      patients with RTMIDs. LIMITATIONS, REASONS FOR CAUTION: The study contained
      appropriate controls, yet the analysis was limited by a small number of control
      patients and embryos. WIDER IMPLICATIONS OF THE FINDINGS: Until now, there had
      been no definite report about the effect of quadrivalents on genome stability in
      reciprocal translocation carriers compared with control samples, and in the
      present study the large sample size ensured a detailed analysis of factors with a
      possible impact on segregation patterns. These data provide a better insight into
      the meiotic mechanisms involved in non-disjunction events in gametes from
      reciprocal translocation carriers. In addition, our results will help to provide
      each reciprocal translocation carrier couple undergoing PGD with more appropriate
      genetic counseling and a better understanding of the large numbers of abnormal
      embryos with chromosome aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): The
      research was supported by the Research Funding of Shanghai Ji Ai Genetics & IVF
      Institute and the authors declare a lack of competing interests in this study.

PMID- 29579271
TI  - Interleukin-34 is present at the fetal-maternal interface and induces
      immunoregulatory macrophages of a decidual phenotype in vitro.
AB  - STUDY QUESTION: Is the newly discovered cytokine interleukin (IL)-34 expressed at
      the human fetal-maternal interface in order to influence polarization of
      monocytes into macrophages of a decidual immunoregulatory phenotype? SUMMARY
      ANSWER: IL-34 was found to be present at the fetal-maternal interface, in both
      fetal placenta and maternal decidua, and it was able to polarize monocytes into
      macrophages of a decidual phenotype. WHAT IS KNOWN ALREADY: IL-34 was shown to
      bind to the same receptor as macrophage-colony stimulating factor (M-CSF), which
      has an important immunomodulatory role at the fetal-maternal interface, for
      example by polarizing decidual macrophages to an M2-like regulatory phenotype. IL
      34 is known to regulate macrophage subsets, such as microglia and Langerhans
      cells, but its presence at the fetal-maternal interface is unknown. STUDY DESIGN,
      SIZE, DURATION: The presence of IL-34 at the fetal-maternal interface was
      evaluated by immunohistochemistry (IHC) and ELISA in placental and decidual
      tissues as well as in isolated trophoblast cells and decidual stromal cells
      obtained from first trimester elective surgical terminations of pregnancy (n =
      49). IL-34 expression was also assessed in third trimester placental biopsies
      from women with (n = 21) or without (n = 15) pre-eclampsia. The effect of IL-34
      on macrophage polarization was evaluated in an in vitro model of blood monocytes
      obtained from healthy volunteers (n = 14). In this model, granulocyte macrophage
      colony stimulating factor (GM-CSF) serves as a growth factor for M1-like
      polarization, and M-CSF as a growth factor for M2-like polarization.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: First trimester placental and decidual
      tissues were obtained from elective pregnancy terminations. Placental biopsies
      were obtained from women with pre-eclampsia and matched controls in the delivery
      ward. Polarization of macrophages in vitro was determined by flow-cytometric
      phenotyping and secretion of cytokines and chemokines in cell-free supernatants
      by multiplex bead assay. MAIN RESULTS AND THE ROLE OF CHANCE: Our study shows
      that IL-34 is produced at the fetal-maternal interface by both placental cyto-
      and syncytiotrophoblasts and decidual stromal cells. We also show that IL-34, in
      vitro, is able to polarize blood monocytes into macrophages with a phenotype
      (CD14highCD163+CD209+) and cytokine secretion pattern similar to that of decidual
      macrophages. The IL-34-induced phenotype was similar, but not identical to the
      phenotype induced by M-CSF, and both IL-34- and M-CSF-induced macrophages were
      significantly different (P < 0.05-0.0001 depending on marker) from GM-CSF
      polarized M1-like macrophages. Our findings suggest that IL-34 is involved in the
      establishment of the tolerant milieu found at the fetal-maternal interface by
      skewing polarization of macrophages into a regulatory phenotype. LIMITATIONS,
      REASONS FOR CAUTION: Although it is clear that IL-34 is present at the fetal
      maternal interface and polarizes macrophages in vitro, its precise role in vivo
      remains to be established. WIDER IMPLICATIONS OF THE FINDINGS: The recently
      discovered cytokine IL-34 is present at the fetal-maternal interface and has
      immunomodulatory properties with regard to induction of decidual macrophages,
      which are important for a healthy pregnancy. Knowledge of growth factors related
      to macrophage polarization can potentially be translated to treatment of
      pregnancy complications involving dysregulation of this process. STUDY
      FUNDING/COMPETING INTEREST(S): This study was funded by grants from the Medical
      Research Council (Grant K2013-61X-22310-01-04), the Research Council of South
      East Sweden (FORSS), and the County Council of Ostergotland, Sweden. No author
      has any conflicts of interest to declare.

PMID- 29579272
TI  - Accuracy of human sperm DNA oxidation quantification and threshold determination
      using an 8-OHdG immuno-detection assay.
AB  - STUDY QUESTION: Can a discriminant threshold be determined for human sperm DNA
      oxidation? SUMMARY ANSWER: A discriminant threshold was found with 65.8% of 8
      hydroxy-2'-deoxyguanosine (8-OHdG)-positive sperm cells and a mean intensity of
      fluorescence (MIF) of 552 arbitrary units. WHAT IS KNOWN ALREADY: Oxidative
      stress is known to interfere with sperm quality and fertilizing capacity.
      However, current practice does not include the routine determination of oxidative
      DNA damage in spermatozoa; optimized consensus protocols are lacking and no
      thresholds of normality have been established. STUDY DESIGN, SIZE, DURATION:
      Intra- and inter-method comparisons between four protocols (I-IV) were conducted
      to determine the most relevant and efficient means of assessing human sperm 8
      OHdG content. Tests of assay repeatability, specificity, sensitivity and
      stability were performed to validate an optimized methodology for routine
      diagnostic use. PARTICIPANTS/MATERIALS, SETTING, METHODS: This prospective study
      compared three immuno-detection methods including immunocytochemistry,
      fluorescence microscopy and flow cytometry. Sperm DNA oxidation for 80 patients
      was determined relative to semen parameters and clinical conditions, using the
      selected immuno-detection protocol in comparison with a commercial kit. These
      patients (age 35 +/- 1 years: mean +/- SEM) presented with normozoospermic (n =
      40) or altered parameters (necro- or/and astheno- or/and teratozoospermia or/and
      leukocytospermia). MAIN RESULTS AND THE ROLE OF CHANCE: Significant positive
      Pearson and Spearman correlations were determined for 8-OHdG values and sperm
      parameters using protocol III. A notable high and positive correlation was
      revealed for MIF with BMI and leukocyte concentration. Protocol III was the most
      discriminating method regarding assay repeatability, specificity, sensitivity,
      stability and reliability for sperm parameter alterations, in particular
      leukocytospermia according to parametric or non-parametric tests, effect-size
      determinations and factorial analysis such as principal component analysis and
      factor discriminant analysis. Of interest is that 39% of the subjects with
      'pathological' sperm DNA oxidation values were normozoospermic. LIMITATIONS,
      REASONS FOR CAUTION: The oligozoospermic population was not evaluated in this
      study because insufficient material was available to carry out the comparisons.
      However, spermatozoa concentration was taken into account in the statistical
      analysis. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first validation
      of a protocol to determine a discriminant threshold for human sperm DNA
      oxidation. The protocol's detection accuracy for 8-OHdG human sperm DNA residues,
      stability over time, and relationship to human sperm quality were demonstrated.
      The assay should find application in the diagnosis of male factor infertility
      associated with oxidative stress. STUDY FUNDING/COMPETING INTEREST(S): This work
      was funded by institutional grants from the CNRS, INSERM and Universite Clermont
      Auvergne (to J.R.D.) and by Clermont-Ferrand Hospital-CECOS research funds (to
      L.J. and F.B.). P.G., A.M., R.J.A. and J.D. are, respectively, CEO, scientific
      director and scientific advisors of a US-based biotech company (Celloxess,
      Princeton, NJ, USA) involved in preventative medicine with a focus on the
      generation of antioxidant oral supplements.

PMID- 29579273
TI  - Thrombopoietin receptor agonist, splenectomy and intravenous immunoglobulin for
      immune thrombocytopaenia with systemic lupus erythematosus.

PMID- 29579274
TI  - Erratum.

PMID- 29579275
TI  - Erratum.

PMID- 29579277
TI  - MRI thermal burn injury: an unrecognized consequence of wearing novel, high-tech
      undergarments.

PMID- 29579279
TI  - Distribution of Eight QT-Prolonging Drugs and Their Main Metabolites Between
      Postmortem Cardiac Tissue and Blood Reveals Potential Pitfalls in Toxicological
      Interpretation.
AB  - Femoral blood concentrations are usually used in postmortem toxicology to assess
      possible toxic effects of drugs. This includes QT-prolongation and other cardiac
      dysrhythmia, which could have been the cause of death. However, blood
      concentration is only a surrogate for the active site concentration, and
      therefore cardiac tissue concentration may provide a more accurate toxicological
      interpretation. Thus, cardiac tissue and femoral and cardiac blood concentrations
      were examined for eight frequently used QT-prolonging drugs (QTD) and their
      metabolites in a mentally ill population. In total, 180 cases were included from
      the Danish autopsy-based forensic study SURVIVE. The concentrations were analyzed
      using ultra-performance liquid chromatography coupled with tandem mass
      spectrometry utilizing stable isotopically labeled internal standards. The
      results showed that the cardiac tissue concentrations were significantly higher
      compared to femoral and cardiac blood concentrations, with two exceptions. The
      median cardiac tissue-to-femoral blood concentration ratio (Kb) ranged from 2.2
      (venlafaxine) to 15 (nortriptyline). The inter-individual fold difference between
      the minimum and maximum Kb ranged from 2.6-fold (Z-hydroxynortriptyline) to 61
      (venlafaxine). For 12 compounds, postmortem redistribution appeared to be
      minimal, whereas four compounds displayed some degree of postmortem
      redistribution. Citalopram and quetiapine were selected for in-depth analysis of
      the relation between the toxicological interpretation and femoral blood/cardiac
      tissue concentrations. Within this dataset, citalopram displayed a wide overlap
      in cardiac tissue concentrations (~50%) between non-toxic and toxic citalopram
      cases, as estimated from femoral blood concentrations. In contrast, quetiapine
      displayed no overlap in cardiac tissue concentrations between non-toxic and toxic
      quetiapine cases based on femoral blood concentrations. The implication of the
      citalopram finding is that possible intoxications can be overlooked when only
      considering femoral blood concentrations. Based on the present findings, non
      toxic cardiac tissue 10th-90th percentile concentration ranges were estimated for
      citalopram (0.93-4.4 mg/kg) and quetiapine (0.0073-0.60 mg/kg).

PMID- 29579280
TI  - Biomarkers enter the world of peripheral artery disease.

PMID- 29579278
TI  - Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus.
AB  - Adult neurogenesis takes place in the brain subventricular zone (SVZ) in the
      lateral walls of lateral ventricles and subgranular zone (SGZ) in the hippocampal
      dentate gyrus (HDG), and functions to supply newborn neurons for normal brain
      functionality. Subchronic Mn exposure is known to disrupt adult neurogenesis in
      the SVZ. This study was designed to determine whether Mn exposure disturbed
      neurogenesis within the adult HDG. Adult rats (10 weeks old) received a single
      dose of bromodeoxyuridine (BrdU) at the end of 4-week Mn exposure to label the
      proliferating cells. Immunostaining and cell counting data showed that BrdU(+)
      cells in Mn-exposed HDG were about 37% lower than that in the control (p < .05).
      The majority of BrdU(+) cells were identified as Sox2(+) cells. Another set of
      adult rats received BrdU injections for 3 consecutive days followed by 2- or 4
      week Mn exposure to trace the fate of BrdU-labeled cells in the HDG. The time
      course studies indicated that Mn exposure significantly reduced the survival rate
      (54% at 2 weeks and 33% at 4 weeks), as compared with that in the control (80% at
      2 weeks and 51% at 4 weeks) (p < .01). A significant time-dependent migration of
      newborn cells from the SGZ toward the granule cell layer was also observed in
      both control and Mn-exposed HDG. Triple-stained neuroblasts and mature neurons
      further revealed that Mn exposure significantly inhibited the differentiation of
      immature neuroblasts into mature neurons in the HDG. Taken together, these
      observations suggest that subchronic Mn exposure results in a reduced cell
      proliferation, diminished survival of adult-born neurons, and inhibited overall
      neurogenesis in the adult HDG. Impaired adult neurogenesis is likely one of the
      mechanisms contribute to Mn-induced Parkinsonian disorder.

PMID- 29579282
TI  - New insights into the regulation of cell cycle.

PMID- 29579281
TI  - Occupational stress and coping mechanisms in crime scene personnel.
AB  - Background: Studies on occupational stress have shown that police officers (POs)
      are vulnerable to the effects of stress, demonstrated by increased risk of
      cardiometabolic diseases, which may be exacerbated by the use of maladaptive
      coping techniques. Although there is an abundance of research pertaining to
      stress in POs, little research has been done to assess a subset of law
      enforcement, crime scene personnel (CSP). Aims: To assess the stress levels,
      anxiety levels and coping mechanisms of CSP across the state of Texas. Methods:
      The Perceived Stress Scale (PSS), Police Stress Questionnaire (PSQ), and the
      Distress Thermometer were used to measure stress levels, the State-Trait Anxiety
      Inventory (STAI) was utilized to measure anxiety, and the Brief COPE
      questionnaire was used to measure coping mechanisms. Results: CSP (N = 76)
      surveyed reported both low stress and low anxiety for all measures used, with
      males reporting slightly higher stress and anxiety than females. Differences in
      coping mechanisms used by CSP were observed between males and females, but not
      between sworn officers and civilian workers. Female CSP used emotional support (P
      < 0.01), instrumental support (P < 0.05) and positive reframing (P < 0.05) as a
      coping mechanism significantly more often than males. Conclusions: The results
      suggest that adaptive coping mechanisms should be emphasized by those supervising
      CSP. With little research available on CSP, further evaluation of the type of
      stressors experienced by these members of law enforcement is warranted.

PMID- 29579283
TI  - Factors associated with positive Mantoux results in NHS healthcare workers.
AB  - Background: The Mantoux method of tuberculin skin testing has been used in
      tuberculosis (TB) screening of healthcare workers (HCWs) in the UK National
      Health Service (NHS) for many years. More recently, there have been problems with
      the supply of the Mantoux test solution presenting a challenge to its continued
      use. Aims: To review results of Mantoux testing and determine factors associated
      with positive Mantoux result, i.e. tuberculin reactivity, in NHS HCWs, with a
      view to streamlining the TB screening process. Methods: A retrospective
      descriptive study. We extracted data on HCW demographics, country of birth,
      previous stay or work in a high TB prevalence country, TB contact, Bacillus
      Calmette-Guerin (BCG) vaccination, previous tuberculin skin test (TST) and
      Mantoux results from the occupational health records of HCWs who had a Mantoux
      test during 1 January 2007 to 31 December 2010 inclusive. Results: We reviewed
      the records of 246 HCWs. Overall, 46% were Mantoux positive (defined as >=6 mm
      skin induration). Factors associated with positive Mantoux result were BCG
      vaccination [odds ratio (OR) 2.30; 95% confidence interval (CI) 1.14-4.66]; stay
      or work in a high TB prevalence country (OR 7.52; CI 2.76-20.46) and previous TST
      (OR 2.78; CI 1.25-6.19). Conclusions: BCG vaccination, stay or work in a high TB
      prevalence country and previous TST were associated with positive Mantoux
      results. These factors could be used to predict Mantoux results, with the
      potential of substituting Mantoux testing.

PMID- 29579284
TI  - Attractor landscape analysis of the cardiac signaling network reveals mechanism
      based therapeutic strategies for heart failure.
AB  - Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart
      failure (HF), a global leading cause of death, and are regulated through the
      complicated intracellular signaling network, limiting the development of
      effective treatments due to its complexity. To identify effective therapeutic
      strategies for HF at a system level, we develop a large-scale comprehensive
      mathematical model of the cardiac signaling network by integrating all available
      experimental evidence. Attractor landscape analysis of the network model
      identifies distinct sets of control nodes that effectively suppress apoptosis and
      hypertrophy of cardiomyocytes under ischemic or pressure overload-induced HF, the
      two major types of HF. Intriguingly, our system-level analysis suggests that
      intervention of these control nodes may increase the efficacy of clinical drugs
      for HF and, of most importance, different combinations of control nodes are
      suggested as potentially effective candidate drug targets depending on the types
      of HF. Our study provides a systematic way of developing mechanism-based
      therapeutic strategies for HF.

PMID- 29579285
TI  - Sublethal Effects of Some Insecticides on Functional Response of Habrobracon
      hebetor (Hymneoptera: Braconidae) When Reared on Two Lepidopteran Hosts.
AB  - The effects of four commonly used pesticides, diazinon (EC 60%), phosalone (EC
      35%), fipronil (Granular formulation 0.2%), and pyriproxifen (EC 10%), on
      functional response of Habrobracon hebetor (Say) (Hymenoptera: Braconidae) were
      investigated using two lepidopteran hosts, Ephestia kuehniella Zeller
      (Lepidoptera: Pyralidae) and Heliothis viriplaca (Hufnagel) (Lepidoptera:
      Noctuidae). Laboratory bioassays determined diazinon and fipronil as highly toxic
      insecticides for all developmental stages of the parasitoid, while the acute
      toxicity of phosalone and pyriproxyfen was moderate to very low depending on the
      life-stage studied. Larval, pupal, and adult stages of the parasitoid were
      exposed to sublethal concentrations (LC30) of insecticides, and the newly mated
      females were used to study functional response of the parasitoid to different
      host densities. With a single exception, a type II functional response was found
      for control and all insecticide treatments on all life stages and both host
      species. All insecticides tended to decrease the asymptote of the functional
      response curve and the maximum parasitism rate, probably by negatively affecting
      the searching efficiency (a') of the parasitoid. These results indicate that the
      control efficiency of parasitoids may be negatively affected by sublethal doses
      of pesticides, even though the type of functional response remains unchanged. As
      a potential solution, appropriate timing of pesticide application is required to
      avoid the antagonistic interactions with natural enemies under integrated
      management programs.

PMID- 29579287
TI  - Prospective Tractography-Based Targeting for Improved Safety of Focused
      Ultrasound Thalamotomy.
AB  - BACKGROUND: Focused ultrasound thalamotomy (FUS-T) was recently approved for the
      treatment of refractory essential tremor (ET). Despite its noninvasive approach,
      FUS-T reinitiated concerns about the adverse effects and long-term efficacy after
      lesioning. OBJECTIVE: To prospectively assess the outcomes of FUS-T in 10 ET
      patients using tractography-based targeting of the ventral intermediate nucleus
      (VIM). METHODS: VIM was identified at the intercommissural plane based on its
      neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed
      at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo,
      were assessed independently by the Tremor Research Group. We analyzed targeting
      coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was
      analyzed in relation to unbiased thalamic parcellation using probabilisitic
      tractography. Quantitative diffusion-weighted imaging changes were also studied
      in fiber tracts of interest. RESULTS: The tractography coordinates were more
      anterior than the standard. Intraoperatively, therapeutic sonications at the
      tractography target improved tremor (>50% improvement) without motor or sensory
      side effects. Sustained improvement in tremor was observed at 3 mo (tremor score:
      18.3 +/- 6.9 vs 8.1 +/- 4.4, P = .001). No motor weakness and sensory deficits
      after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3
      patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic
      tractography. Significant microstructural changes were observed in the white
      matter connecting VIM with cerebellum and motor cortex. CONCLUSION: This is the
      first report of prospective VIM targeting with tractography for FUS-T. These
      results suggest that tractography-guided targeting is safe and has satisfactory
      short-term clinical outcomes.

PMID- 29579286
TI  - Involvement of Heparanase in the Pathogenesis of Mesothelioma: Basic Aspects and
      Clinical Applications.
AB  - Background: Mammalian cells express a single functional heparanase, an
      endoglycosidase that cleaves heparan sulfate and thereby promotes tumor
      metastasis, angiogenesis, and inflammation. Malignant mesothelioma is highly
      aggressive and has a poor prognosis because of the lack of markers for early
      diagnosis and resistance to conventional therapies. The purpose of this study was
      to elucidate the mode of action and biological significance of heparanase in
      mesothelioma and test the efficacy of heparanase inhibitors in the treatment of
      this malignancy. Methods: The involvement of heparanase in mesothelioma was
      investigated by applying mouse models of mesothelioma and testing the effect of
      heparanase gene silencing (n = 18 mice per experiment; two different models) and
      heparanase inhibitors (ie, PG545, defibrotide; n = 18 per experiment; six
      different models). Synchronous pleural effusion and plasma samples from patients
      with mesothelioma (n = 35), other malignancies (12 non-small cell lung cancer,
      two small cell lung carcinoma, four breast cancer, three gastrointestinal
      cancers, two lymphomas), and benign effusions (five patients) were collected and
      analyzed for heparanase content (enzyme-linked immunosorbent assay). Eighty-one
      mesothelioma biopsies were analyzed by H-Score for the prognostic impact of
      heparanase using immunohistochemistry. All statistical tests were two-sided.
      Results: Mesothelioma tumor growth, measured by bioluminescence or tumor weight
      at termination, was markedly attenuated by heparanase gene silencing (P = .02)
      and by heparanase inhibitors (PG545 and defibrotide; P < .001 and P = .01,
      respectively). A marked increase in survival of the mesothelioma-bearing mice (P
      < .001) was recorded. Heparanase inhibitors were more potent in vivo than
      conventional chemotherapy. Clinically, heparanase levels in patients' pleural
      effusions could distinguish between malignant and benign effusions, and a
      heparanase H-score above 90 was associated with reduced patient survival (hazard
      ratio = 1.89, 95% confidence interval = 1.09 to 3.27, P = .03). Conclusions: Our
      results imply that heparanase is clinically relevant in mesothelioma development.
      Given these preclinical and clinical data, heparanase appears to be an important
      mediator of mesothelioma, and heparanase inhibitors are worthy of investigation
      as a new therapeutic modality in mesothelioma clinical trials.

PMID- 29579288
TI  - Clinical Characterization of Invasive Disease Caused by Haemophilus influenzae
      Serotype b in a High Vaccination Coverage Setting.
AB  - This national study characterized invasive Haemophilus influenzae serotype b
      infections. Vaccinated (n = 41) and nonvaccinated (n = 10) cases were similar
      regarding presentation as meningitis (68.8% vs 90.0%; P = .25), predisposing
      factors (29.3% vs 20.0%; P = .76), admission to intensive care unit or death
      (22.0% vs 10.0%; P = 1.00), or sequelae (21.6% vs 10.0%; P = .81). Haemophilus
      influenzae serotype b occurred in vaccinated, healthy children with comparable
      disease course.

PMID- 29579289
TI  - Comparative efficacy of individual renin-angiotensin system inhibitors on major
      renal outcomes in diabetic kidney disease: a network meta-analysis.
AB  - Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
      receptor blockers (ARBs) are two drug classes with well-documented renal
      protective effects. However, whether there is any difference among individual
      drugs remains unknown. In this study, we aimed to compare the efficacy of
      individual ACEIs/ARBs on major renal outcomes in adults with diabetic kidney
      disease (DKD). Methods: We conducted a Bayesian-framework network meta-analysis
      with a random effects model. We searched PubMed, Embase, Scopus, the Cochrane
      Central Register of Controlled Trials and ClinicalTrials.gov for clinical trials
      of ACEIs or ARBs as monotherapy compared with other conventional antihypertensive
      drugs or placebo. Primary outcomes were end-stage renal disease (ESRD) and
      albuminuria/proteinuria (including change in albuminuria/proteinuria, progression
      to macroalbuminuria and remission to normoalbuminuria). Secondary outcome was
      doubling of serum creatinine levels. We also assessed for hyperkalemia, cough and
      angioedema/edema. International prospective register of systematic reviews
      (PROSPERO) registration CRD42016036997. Results: A total of 100 studies with data
      for 22 365 DKD patients, the majority of whom had type 2 diabetes, were included.
      Individual ACEIs and ARBs at goal doses showed no significant differences in ESRD
      and doubling of serum creatinine levels. They also shared similar effects on
      albuminuria/proteinuria reduction and progression or remission of albuminuria.
      When combining three outcomes of albuminuria/proteinuria as a single endpoint,
      most ACEIs/ARBs consistently showed favorable antiproteinuric effect, with little
      difference in the possibility of being the superior treatment for improving
      albuminuria/proteinuria. Primary outcomes did not change substantially in meta
      regressions and sensitivity analyses. Findings were limited by lack of dose
      equivalence and paucity of data for some outcomes. Conclusions: Based on the
      available evidence, individual ACEIs and ARBs at goal doses appeared to have no
      or little differences in their effect on major renal outcomes.

PMID- 29579290
TI  - The impact of outpatient acute kidney injury on mortality and chronic kidney
      disease: a retrospective cohort study.
AB  - Background: Acute kidney injury (AKI) has been extensively studied in hospital
      settings. Limited data exist regarding outcomes for patients with outpatient AKI
      who are not subsequently admitted. We investigated whether outpatient AKI,
      defined by a 50% increase in creatinine (Cr), is associated with increased
      mortality and renal events. Methods: In this retrospective study, outpatient
      serum Cr values from adults receiving primary care at a health system during an
      18-month exposure period were used to categorize patients into one of five groups
      (no outpatient AKI, outpatient AKI with recovery, outpatient AKI without
      recovery, outpatient AKI without repeat Cr and no Cr). Principal outcomes of all
      cause mortality and renal events (50% decline in estimated glomerular filtration
      rate to <30 mL/min/1.73 m2) were examined using Cox proportional hazards models.
      Results: Among 384 869 eligible patients, 51% had at least one Cr measured during
      the exposure period. Outpatient AKI occurred in 1.4% of patients while hospital
      AKI occurred in only 0.3% of patients. The average follow-up was 5.3 years.
      Outpatient AKI was associated with an increased risk of all-cause mortality
      {adjusted hazard ratio [aHR] 1.90 [95% confidence interval (CI) 1.76-2.06]} and
      results were consistent across all AKI groups. Outpatient AKI was also associated
      with an increased risk of renal events [aHR 1.33 (95% CI 1.11-1.59)], even among
      those who recovered. Conclusions: Outpatient AKI is more prevalent than inpatient
      AKI and is a risk factor for all-cause mortality and renal events, even among
      those who recover kidney function. Further research is necessary to determine
      risk factors and identify strategies for preventing outpatient AKI.

PMID- 29579291
TI  - Sporadic inclusion body myositis: magnetic resonance imaging and ultrasound
      characteristics.

PMID- 29579292
TI  - Do atmospheric CO2 concentration increase, climate and forest management affect
      iWUE of common beech? Evidences from carbon isotope analyses in tree rings.
AB  - Beech is one of the most important forest tree species in Europe, hence possible
      adverse factors affecting its physiology and productivity can have strong
      ecological and economic impacts. In this context, four beech forests along a
      latitudinal gradient from southern Apennines to middle European lowlands were
      selected for chronological determinations of carbon isotope composition
      (delta13C) in tree-ring cellulose. The main objectives of this study were to
      assess (i) the effect of climate on the carbon signature of tree-ring cellulose
      (delta13C); (ii) the physiological response to recent CO2 concentration increment
      and to climatic variation; and (iii) the relationship between intrinsic water-use
      efficiency (iWUE, here the average long-term ratio of net photosynthesis to
      stomatal conductance) and growth of trees in different sites since 1950. Our
      results demonstrated that site climatic conditions peculiarly affect delta13C. In
      northern sites, a climatic control of summer precipitation and temperature on
      stomatal conductance was demonstrated by their opposite correlations with
      delta13C, negative and positive, respectively. Furthermore, an 'earliness effect'
      was suggested by a significant relationship between spring temperature and
      delta13C in the coldest sites and by a positive one between winter temperature
      and delta13C in the warmest ones. In all the study sites, during the maturity
      phase, a positive correlation between the increment of CO2 and iWUE was observed,
      due to an active response of trees to CO2 increment. This increment of CO2 was
      the main driver of the long term increasing trend of iWUE, resulting by an active
      response of trees to CO2 fertilization. Moreover, precipitation mostly influences
      positively and negatively the inter-annual variations of iWUE of the southernmost
      and northernmost sites, respectively. Overall, we observed a mean increment of
      40% of iWUE. Moreover, the sensitivity of iWUE to the increase of CO2 was
      different between the northernmost and southernmost sites. Increasing iWUE was
      correlated to growth in the two sites during the release phase and we hypothesize
      a positive effect of silvicultural treatments.

PMID- 29579293
TI  - Engaging workplace representatives in research: what recruitment strategies work
      best?
AB  - Background: Workplaces are key stakeholders in work and health but little is
      known about the methods used to recruit workplace representatives (WRs),
      including managers, occupational health advisers and colleagues, to externally
      funded healthcare research studies. Aims: To detail the strategies used in
      recruiting WRs from three areas of the UK to a qualitative study concerning their
      experience of employees undergoing hip or knee replacement, to compare the
      strategies and inform recruitment methods for future studies. Methods: Six
      strategies were used to recruit WRs from organizations of different sizes and
      sectors. Data on numbers approached and responses received were analysed
      descriptively. Results: Twenty-five WRs were recruited. Recruitment had to be
      extended outside the main three study areas, and took several months. It proved
      more difficult to recruit from non-service sectors and small- and medium-sized
      enterprises. The most successful strategies were approaching organizations that
      had participated in previous research studies, or known professionally or
      personally to team members. Conclusions: Recruiting a diverse sample of WRs to
      healthcare research requires considerable resources and persistence, and a range
      of strategies. Recruitment is easier where local relationships already exist; the
      importance of building and maintaining these relationships cannot be
      underestimated. However, the potential risks of bias and participant fatigue need
      to be acknowledged and managed. Further studies are needed to explore how WRs can
      be recruited to health research, and to identify the researcher effort and costs
      involved in achieving unbiased and representative samples.

PMID- 29579294
TI  - Topical Review: Perfectionism and Pediatric Chronic Pain: Theoretical
      Underpinnings, Assessment, and Treatment.
AB  - Objective: To use the biopsychosocial model and current literature to clarify
      conceptual underpinnings between chronic pain and perfectionism in youth, provide
      recommendations for assessment and treatment of co-existing perfectionism and
      chronic pain conditions, and suggest a research agenda. Methods: Current
      literature is used to identify biopsychosocial factors common between pediatric
      chronic pain and perfectionism, preliminary research findings are presented, and
      suggestions are made for research that will help inform inclusion and adaptations
      of assessment tools and interventions to address perfectionism. Results:
      Biopsychosocial factors that may contribute to the observed relationship between
      chronic pain and perfectionism seen in many youth are identified. For example,
      cognitive factors known to be associated with perfectionism (e.g., rumination)
      may also contribute to pain-related catastrophizing and disability.
      Biopsychosocial factors may serve as mediating variables between perfectionism
      and pain-related outcomes among youth with chronic pain and their parents.
      Conclusions: Research assuming a biopsychosocial perspective is needed to clarify
      observed links between chronic pain and perfectionism in youth. Findings related
      to the characterization of perfectionism in pediatric chronic pain will inform
      how assessment and treatment tools can better identify and address perfectionism.

PMID- 29579295
TI  - Introduction to the Special Issue: Advances in Behavioral and Psychological Pain
      Research in Children: From Prevention Through Chronic Pain Management.

PMID- 29579296
TI  - Cockroach Ancient Geographic and Genomic History Traced Back to Last
      Supercontinent.

PMID- 29579297
TI  - Bringing Water to the Fountain of Youth: How New Evidence of Sex Reversals Helps
      Show How Sex Chromosomes Are Maintained over Evolutionary Time.

PMID- 29579298
TI  - Long-lasting Glucagon-like Peptide 1 Analogue Exendin-4 Ameliorates the Secretory
      and Synthetic Function of Islets Isolated From Severely Scalded Rats.
AB  - The aim of this article was to observe the intracellular insulin content of
      islets isolated from severely scalded and Exendin-4-treated rats and to evaluate
      the stimulation of insulin mRNA synthesis and secretion by beta cells at
      different glucose concentrations and during different periods of time. A 50% TBSA
      full-thickness scalded rat model was used. Rats were treated with Exendin-4,
      followed by islet isolation and functional measurements. Serum was collected for
      detection of serum insulin, glucose, and glucagon levels. Intracellular insulin
      content was determined by transmission electron microscopy. Isolated islets were
      incubated with different glucose concentrations for 1 or 24 hours to assess the
      effect of scalding with or without Exendin-4 treatment on functional parameters.
      Insulin secretion was analyzed by enzyme-linked immunosorbent assay.
      Intracellular insulin and proinsulin content were analyzed by
      immunoprecipitation. Islet preproinsulin mRNA expression was examined by real
      time polymerase chain reaction. Transmission electron microscopy analyses showed
      that severe thermal injury significantly reduced the number of insulin granules
      per micrometer2. Insulin secretion and intracellular insulin and proinsulin
      levels were markedly reduced in islets stimulated with different glucose
      concentrations; chronic high-glucose-stimulated islet preproinsulin mRNA
      expression was also impaired. Exendin-4 treatment after thermal trauma improved
      the number of intracellular insulin granules. Exendin-4 improved both insulin
      secretion and intracellular insulin reserves under different glucose stimulation
      conditions. Islet insulin mRNA expression was also restored by Exendin-4
      treatment. Exendin-4 can restore the islet beta cell insulin reserve following
      severe scald injury and may also improve insulin secretion, insulin reserve, and
      mRNA expression in islet beta cells.

PMID- 29579299
TI  - Overexpression of PeMIPS1 confers tolerance to salt and copper stresses by
      scavenging reactive oxygen species in transgenic poplar.
AB  - Myo-inositol is a vital compound in plants. As the key rate-limiting enzyme in
      myo-inositol biosynthesis, l-myo-inositol-1-phosphate synthase (MIPS) is regarded
      as a determinant of the myo-inositol content in plants. The up-regulation of MIPS
      genes can increase the myo-inositol content, thereby enhancing the plant's
      resistance to a variety of stresses. However, there are few reports on the roles
      of myo-inositol and the identification of MIPS in woody trees. In this study, a
      MIPS gene, named as PeMIPS1, was characterized from Populus euphratica Oliv. The
      heterologous expression of PeMIPS1 compensated for inositol production in the
      yeast inositol auxotrophic mutant ino1 and the phenotypic lesions of the atmips1
      2 mutant, an Arabidopsis MIPS1 knock-out mutant. A subcellular location analysis
      showed that the PeMIPS1-GFP fusion was localized in the nucleus and cytoplasm,
      but not in the chloroplasts, indicating that PeMIPS1 represented the cytosolic
      form of MIPS in P. euphratica. Interestingly, PeMIPS1 was not only inducible by
      drought and high salinity, but also by CuSO4 treatment. The transgenic poplar
      lines overexpressing PeMIPS1 had greater plant heights, shoot biomasses and
      survival rates than the wild type during the salt- or copper-stress treatment,
      and this was accompanied by an increase in the myo-inositol content. The
      overexpression of PeMIPS1 resulted in the increased activities of antioxidant
      enzymes and the accumulation of ascorbate, a key nonenzymatic antioxidant in
      plant, which partly accounted for the enhanced reactive oxygen species-scavenging
      capacity and the lowered hydrogen peroxide and malondialdehyde levels in the
      transgenic poplar. To the best of our knowledge, this study is the first to
      report the roles of MIPS genes in the tolerance to copper stress.

PMID- 29579300
TI  - Forgiveness, spirituality and love: thematic analysis of last statements from
      Death Row, Texas (2002-17).
AB  - Background: Psychological features associated with execution are not fully
      understood. Aims: To analyse demographics of individuals executed in Texas and
      investigate whether there has been any change in common themes and psychological
      factors evident in last statements before execution between 2002 and 2017.
      Design: Analysis of last statements from Death Row, Texas. Methods: We (a)
      studied themes and psychological factors in last statements in Texas between
      August 2011 and May 2017; and (b) combined our 2011-17 data with our previous
      data (2002-06 and 2006-11) to present an overall analysis of last statements from
      2002 to 2017. Results: Between April 2002 and May 2017 (279 executions; 240 last
      statements), the execution rate in Texas fell from 25 per year to 12; median time
      on death row increased from 108.5 months to 149.5; median age at execution
      increased from 38 years to 40.5; and the proportion of offences involving
      multiple victims rose from 28.4% to 47.1%. The most common themes in last
      statements were love (78%), spirituality (58%), regret (35%) and apology (35%).
      The most common psychological factors were identification-egression (51%),
      unbearable psychological pain (47%) and rejection-aggression (40%). Two themes
      (forgiveness, use of poetry/literature) and three psychological factors
      (inability to adjust, interpersonal relations, identification-egression) became
      less common. Conclusions: Between 2002 and 2017, executed prisoners in Texas
      became fewer and older, spent longer on death row and had committed more serious
      offences. Themes of love and spirituality were constants, but requests for
      forgiveness declined.

PMID- 29579301
TI  - Functional characteristics of phenolic compounds accumulated in young leaves of
      two subtropical forest tree species of different successional stages.
AB  - The abundance of phenolic compounds (including anthocyanins) in leaves is
      associated with photosynthetic performance, but the regulatory mechanism is
      unclear. Schima superba Gardn. et Champ. and Cryptocarya concinna Hance., which
      exhibit distinct anthocyanin accumulation patterns, are dominant tree species in
      the early- and late-successional stages, respectively, of subtropical forests in
      China. RNA-seq and analyses of phenolic concentrations, antioxidant capacity and
      photosynthetic characteristics were performed on young and mature leaves of these
      two species under contrasting light conditions. The high-light-acclimated young
      leaves of S. superba and C. concinna and low-light-acclimated young leaves of C.
      concinna were red. These red leaves had higher ratios of electron transport rate
      to gross photosynthesis (ETR:Pgross) and total antioxidant capacity to
      chlorophyll (TAC:Chl) than did the green leaves, regardless of light conditions.
      In addition, the red leaves had a higher expression level of the UDP
      glucose:flavonoid 3-O-glucosyltransferase (UFGT) gene than did the green leaves,
      irrespective of light conditions. Total antioxidant capacity was positively
      correlated with flavonoid content in C. concinna leaves and with total phenolic
      content in leaves of both species under both high and low light. Consistent with
      the measurements of photosynthetic performance and flavonoids:Chl ratio,
      photosynthesis-related genes were extensively downregulated and flavonoid-pathway
      related genes were extensively upregulated in young leaves relative to mature
      leaves. Under high and low light, both non-photochemical quenching and TAC:Chl,
      which serve as different types of photoprotective tools, were enhanced in young
      leaves of S. superba, whereas only TAC:Chl was enhanced in young leaves of C.
      concinna. Our results indicate that the biosynthesis of phenolic compounds in
      young leaves is likely enhanced by an imbalance between photosynthetic electron
      supply and demand and that flavonoids play a larger role in meditating
      photoprotection in late-successional species than in early-successional ones.

PMID- 29579276
TI  - Contributions of mean and shape of blood pressure distribution to worldwide
      trends and variations in raised blood pressure: a pooled analysis of 1018
      population-based measurement studies with 88.6 million participants.
AB  - Background: Change in the prevalence of raised blood pressure could be due to
      both shifts in the entire distribution of blood pressure (representing the
      combined effects of public health interventions and secular trends) and changes
      in its high-blood-pressure tail (representing successful clinical interventions
      to control blood pressure in the hypertensive population). Our aim was to
      quantify the contributions of these two phenomena to the worldwide trends in the
      prevalence of raised blood pressure. Methods: We pooled 1018 population-based
      studies with blood pressure measurements on 88.6 million participants from 1985
      to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic
      blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year
      age group from 20-29 years to 70-79 years in each study, taking into account
      complex survey design and survey sample weights, where relevant. We used a linear
      mixed effect model to quantify the association between (probit-transformed)
      prevalence of raised blood pressure and age-group- and sex-specific mean blood
      pressure. We calculated the contributions of change in mean SBP and DBP, and of
      change in the prevalence-mean association, to the change in prevalence of raised
      blood pressure. Results: In 2005-16, at the same level of population mean SBP and
      DBP, men and women in South Asia and in Central Asia, the Middle East and North
      Africa would have the highest prevalence of raised blood pressure, and men and
      women in the high-income Asia Pacific and high-income Western regions would have
      the lowest. In most region-sex-age groups where the prevalence of raised blood
      pressure declined, one half or more of the decline was due to the decline in mean
      blood pressure. Where prevalence of raised blood pressure has increased, the
      change was entirely driven by increasing mean blood pressure, offset partly by
      the change in the prevalence-mean association. Conclusions: Change in mean blood
      pressure is the main driver of the worldwide change in the prevalence of raised
      blood pressure, but change in the high-blood-pressure tail of the distribution
      has also contributed to the change in prevalence, especially in older age groups.

PMID- 29579302
TI  - Community-acquired pneumonia and Gram-negative bacilli in Cambodia-incidence,
      risk factors and clinical characteristics.
AB  - Background: In Western settings, community-acquired pneumonia (CAP) due to Gram
      negative bacilli (GNB) is relatively rare. Previous studies from Asia, however,
      indicate a higher prevalence of GNB in CAP, but data, particularly from Southeast
      Asia, are limited. Methods: This is a prospective observational study of 1451
      patients >=15 y of age with CAP from two hospitals in Cambodia between 2007 and
      2010. The proportion of GNB was estimated. Risk factors and clinical
      characteristics of CAP due to GNB were assessed using logistic regression models.
      Results: The prevalence of GNB was 8.6% in all CAP patients and 15.8% among those
      with a valid respiratory sample. GNB infection was independently associated with
      diabetes, higher leucocyte count and CAP severity. Mortality was higher in
      patients with CAP due to GNB. Conclusions: We found a high proportion of GNB in a
      population hospitalized for CAP in Cambodia. Given the complex antimicrobial
      sensitivity patterns of certain GNBs and the rapid emergence of multidrug
      resistant GNB, microbiological laboratory capacity should be strengthened and
      prospective clinical trials comparing empiric treatment algorithms according to
      the severity of CAP are needed.

PMID- 29579303
TI  - Impact of the bicuspid aortic valve on aortic root haemodynamics: three
      dimensional computed fluid dynamics simulation.
AB  - OBJECTIVES: The aim was to evaluate the impact of a bicuspid aortic valve (BAV)
      on local shear stress and on the pressure profile on the elements of the aortic
      root (AoR). METHODS: The experiment setup included a BAV with aortic valve
      stenosis (n = 5 pigs, 67 +/- 3.5 kg) and insufficiency (n = 5 pigs, 66.7 +/- 4.4
      kg). By implanting 6 high-fidelity microsonometric crystals in each AoR, we
      determined the 3-dimensional (3D) geometry of the AoR. Experimental and geometric
      data were used to create a 3D time- and pressure-dependent computed fluid dynamic
      model of the AoR with the BAV. RESULTS: 3D AoR geometry was determined by AoR
      tilt (alpha) and rotation angle (beta). Both values were maximal at the end of
      diastole: 24.41 +/- 1.70 degrees  (alpha) and 20.90 +/- 2.11 degrees  (beta) for
      BAV with stenosis and 31.92 +/- 11.51 degrees  (alpha) and 20.84 +/- 9.80 degrees
      (beta) for BAV with insufficiency and minimal at peak ejection 23.42 +/- 1.65
      degrees  (alpha), 20.38 +/- 1.61 degrees  (beta) for stenosis and 26.62 +/- 7.86
      degrees  (alpha), 19.79 +/- 8.45 degrees  (beta) for insufficiency. In
      insufficiency, low shear stress of 0-0.08 Pa and moderate pressure (60-80 mmHg)
      were present. In BAV with stenosis, low shear stress of 0-0.5 Pa and moderate
      pressure (0-20 mmHg) were present at diastole; at peak ejection high shear stress
      >2 Pa and elevated pressure of >80 mmHg were present. CONCLUSIONS: In a BAV with
      aortic valve stenosis, the haemodynamics are less favourable. The elevated
      pressure with elevated shear stress may over the long term promote degenerative
      processes in the leaflets and consequently valve function failure.

PMID- 29579304
TI  - Molecular cloning and characterization of a brassinosteriod biosynthesis-related
      gene PtoDWF4 from Populus tomentosa.
AB  - Brassinosteroids (BRs) as steroid hormones play an important role in plant growth
      and development. However, little is known about how BRs affect secondary wall
      biosynthesis in woody plants. In this study, we cloned and characterized PtoDWF4,
      a homologus gene of Arabidopsis DWF4 encoding a cytochrome P450 protein, from
      Populus tomentosa. qRT-PCR analysis showed that PtoDWF4 was highly expressed in
      stems, especially in xylem. Overexpression of PtoDWF4 (PtoDWF4-OE) in poplar
      promoted growth rate and biomass yield, increased area and cell layers of xylem.
      Transgenic plants showed a significant increase in plant height and stem diameter
      compared with the wild type. In contrast, the CRISPR/Cas9-generated mutation of
      PtoDWF4 (PtoDWF4-KO) resulted in significantly decreased biomass production in
      transgenic plants. Further studies revealed that constitutive expression of
      PtoDWF4 up-regulated the expression of secondary cell wall (SCW) biosynthesis
      related genes, whereas knock-out of PtoDWF4 down-regulated their expression.
      Quantitative analysis of cell wall components showed a significant increase in
      PtoDWF4-OE lines but a reduction in PtoDWF4-KO lines compared with wild-type
      plants. Taken together, our results indicate that PtoDWF4 plays a positive role
      in improving growth rate and elevating biomass production in poplar.

PMID- 29579305
TI  - Seizure outcomes of supratentorial brain tumor resection in pediatric patients.
AB  - Background: This study aims to identify the prevalence of and risk factors for
      seizure development after supratentorial brain tumor resection in pediatric
      patients. This could be used to guide the postoperative management and usage of
      anti-epileptic drugs (AEDs). Methods: Retrospective study was conducted for
      patients between 0 and 21 years with supratentorial tumor resection between 2005
      and 2015 at a single institution. Results: Two hundred patients (114 males/86
      females) were identified. Median age at resection (+/-SD) was 9.025 +/- 5.720
      years and mean follow-up was 4 +/- 2 years. Resection was gross total in 82
      patients (41%) and partial in 118 patients (59%); 66 patients (33%) experienced
      preoperative seizures, and 67 patients (34%) experienced postoperative seizures;
      18 patients (27%) had early seizures, and 49 patients (73%) had late seizures.
      Univariate analysis identified risk factors for postoperative seizures as:
      preoperative seizures (P < 0.001), age less than 2 years (P = 0.003), temporal
      location (P < 0.001), thalamic location (P = 0.017), preoperative hyponatremia (P
      = 0.017), World Health Organization grade (P = 0.008), and pathology (P = 0.005).
      Multivariate regression identified 5 robust risk factors: temporal location (odds
      ratio [OR] 4.7, 95% CI: 1.7-13.3, P = 0.003), age <2 years (OR 3.9, 95% CI: 1.0
      15.4; P = 0.049), preoperative hydrocephalus (OR 3.8, 95% CI: 1.5-9.4; P =
      0.005), preoperative seizure (OR 2.8, 95% CI: 1.2-6.5; P = 0.016) and parietal
      location (OR 0.25, 95% CI: 0.06-0.99; P = 0.049). Extent of resection did not
      correlate with seizure development (P > 0.05). Conclusions: This study reveals 5
      risk factors for postoperative seizures after resection of supratentorial tumors.
      These factors should be considered in postoperative management of these patients.

PMID- 29579306
TI  - A Novel Multifunctional C-23 Oxidase, CYP714E19, is Involved in Asiaticoside
      Biosynthesis.
AB  - Centella asiatica is widely used as a medicinal plant due to accumulation of the
      ursane-type triterpene saponins asiaticoside and madecassoside. The molecular
      structure of both compounds suggests that they are biosynthesized from alpha
      amyrin via three hydroxylations, and the respective Cyt P450-dependent
      monooxygenases (P450 enzymes) oxidizing the C-28 and C-2alpha positions have been
      reported. However, a third enzyme hydroxylating C-23 remained elusive. We
      previously identified 40,064 unique sequences in the transcriptome of C. asiatica
      elicited by methyl jasmonate, and among them we have now found 149 unigenes
      encoding putative P450 enzymes. In this set, 23 full-length cDNAs were
      recognized, 13 of which belonged to P450 subfamilies previously implicated in
      secondary metabolism. Four of these genes were highly expressed in response to
      jasmonate treatment, especially in leaves, in accordance with the accumulation
      patterns of asiaticoside. The functions of these candidate genes were tested
      using heterologous expression in yeast cells. Gas chromatography-mass
      spectrometry (GC-MS) analysis revealed that yeast expressing only the
      oxidosqualene synthase CaDDS produced the asiaticoside precursor alpha-amyrin
      (along with its isomer beta-amyrin), while yeast co-expressing CaDDS and
      CYP716A83 also contained ursolic acid along with oleanolic acid. This P450 enzyme
      thus acts as a multifunctional triterpenoid C-28 oxidase converting amyrins into
      corresponding triterpenoid acids. Finally, yeast strains co-expressing CaDDS,
      CYP716A83 and CYP714E19 produced hederagenin and 23-hydroxyursolic acid, showing
      that CYP714E19 is a multifunctional triterpenoid oxidase catalyzing the C-23
      hydroxylation of oleanolic acid and ursolic acid. Overall, our results
      demonstrate that CaDDS, CYP716A83 and CYP714E19 are C. asiatica enzymes
      catalyzing consecutive steps in asiaticoside biosynthesis.

PMID- 29579307
TI  - A threonyl-tRNA synthetase-like protein has tRNA aminoacylation and editing
      activities.
AB  - TARS and TARS2 encode cytoplasmic and mitochondrial threonyl-tRNA synthetases
      (ThrRSs) in mammals, respectively. Interestingly, in higher eukaryotes, a third
      gene, TARSL2, encodes a ThrRS-like protein (ThrRS-L), which is highly homologous
      to cytoplasmic ThrRS but with a different N-terminal extension (N-extension).
      Whether ThrRS-L has canonical functions is unknown. In this work, we studied the
      organ expression pattern, cellular localization, canonical aminoacylation and
      editing activities of mouse ThrRS-L (mThrRS-L). Tarsl2 is ubiquitously but
      unevenly expressed in mouse tissues. Different from mouse cytoplasmic ThrRS
      (mThrRS), mThrRS-L is located in both the cytoplasm and nucleus; the nuclear
      distribution is mediated via a nuclear localization sequence at its C-terminus.
      Native mThrRS-L enriched from HEK293T cells was active in aminoacylation and
      editing. To investigate the in vitro catalytic properties of mThrRS-L accurately,
      we replaced the N-extension of mThrRS-L with that of mThrRS. The chimeric protein
      (mThrRS-L-NT) has amino acid activation, aminoacylation and editing activities.
      We compared the activities and cross-species tRNA recognition between mThrRS-L-NT
      and mThrRS. Despite having a similar aminoacylation activity, mThrRS-L-NT and
      mThrRS exhibit differences in tRNA recognition and editing capacity. Our results
      provided the first analysis of the aminoacylation and editing activities of ThrRS
      L, and improved our understanding of Tarsl2.

PMID- 29579308
TI  - The effect of albendazole treatment on non-seizure outcomes in patients with
      symptomatic neurocysticercosis.
AB  - Background: There is little information about the impact of anthelminthic
      treatment on clinical symptoms other than seizures in neurocysticercosis (NC). We
      investigated the effect of albendazole on non-seizure symptoms experienced by
      patients with NC. Methods: Data are from a randomized controlled trial comparing
      albendazole plus prednisone with placebo plus prednisone for treatment of NC
      among 173 patients with active or transitional NC cysts and new-onset symptoms.
      We performed negative binomial regression to examine the number of follow-up
      visits when a symptom was reported, logistic regression to examine the
      probability of experiencing the symptom and Cox proportional hazards models to
      examine the time to first reporting the symptom. Results: Eighty-five percent of
      patients reported at least one non-seizure symptom at baseline. Those treated
      with albendazole had significantly lower odds of memory loss and/or confusion
      during months 1-24 (odds ratio [OR] 0.42, p=0.037) and significantly increased
      odds of anxiety and/or depression during months 1-12 (OR 1.87, p=0.049). No
      treatment difference existed in experiencing symptoms in general or in
      experiencing headaches, limb weakness or gait disturbances, vomiting, nausea
      and/or stomach pain or visual disturbances over the follow-up period.
      Conclusions: While the prevalence of non-seizure symptoms was high, albendazole
      treatment was associated with only two significant differences in the non-seizure
      symptoms over follow-up. Further research is needed to identify strategies to
      reduce the long-term symptom burden in patients with NC.

PMID- 29579309
TI  - ViFi: accurate detection of viral integration and mRNA fusion reveals
      indiscriminate and unregulated transcription in proximal genomic regions in
      cervical cancer.
AB  - The integration of viral sequences into the host genome is an important driver of
      tumorigenesis in many viral mediated cancers, notably cervical cancer and
      hepatocellular carcinoma. We present ViFi, a computational method that combines
      phylogenetic methods with reference-based read mapping to detect viral
      integrations. In contrast with read-based reference mapping approaches, ViFi is
      faster, and shows high precision and sensitivity on both simulated and biological
      data, even when the integrated virus is a novel strain or highly mutated. We
      applied ViFi to matched genomic and mRNA data from 68 cervical cancer samples
      from TCGA and found high concordance between the two. Surprisingly, viral
      integration resulted in a dramatic transcriptional upregulation in all proximal
      elements, including LINEs and LTRs that are not normally transcribed. This
      upregulation is highly correlated with the presence of a viral gene fused with a
      downstream human element. Moreover, genomic rearrangements suggest the formation
      of apparent circular extrachromosomal (ecDNA) human-viral structures. Our results
      suggest the presence of apparent small circular fusion viral/human ecDNA, which
      correlates with indiscriminate and unregulated expression of proximal genomic
      elements, potentially contributing to the pathogenesis of HPV-associated cervical
      cancers. ViFi is available at https://github.com/namphuon/ViFi.

PMID- 29579310
TI  - Transcriptional and epigenetic adaptation of maize chromosomes in Oat-Maize
      addition lines.
AB  - By putting heterologous genomic regulatory systems into contact, chromosome
      addition lines derived from interspecific or intergeneric crosses allow the
      investigation of transcriptional regulation in new genomic environments. Here, we
      report the transcriptional and epigenetic adaptation of stably inherited alien
      maize chromosomes in two oat-maize addition (OMA) lines. We found that the
      majority of maize genes displayed maize-specific transcription in the oat genomic
      environment. Nevertheless, a quarter of the expressed genes encoded by the two
      maize chromosomes were differentially expressed genes (DEGs). Notably, highly
      conserved orthologs were more severely differentially expressed in OMAs than less
      conserved orthologs. Additionally, syntenic genes and highly abundant genes were
      over-represented among DEGs. Gene suppression was more common than activation
      among the DEGs; however, the genes in the former maize pericentromere, which
      expanded to become the new centromere in OMAs, were activated. Histone
      modifications (H3K4me3, H3K9ac and H3K27me3) were consistent with these
      transcriptome results. We expect that cis regulation is responsible for unchanged
      expression in OMA versus maize; and trans regulation is the predominant mechanism
      behind DEGs. The genome interaction identified here reveals the important
      consequences of interspecific/intergeneric crosses and potential mechanisms of
      plant evolution when genomic environments interact.

PMID- 29579311
TI  - Strength and Cardiorespiratory Exercise Rehabilitation for Severely Burned
      Patients During Intensive Care Units: A Survey of Practice.
AB  - Minimizing the deconditioning of burn injury through early rehabilitation
      programs (RP) in the intensive care unit (ICU) is of importance for improving the
      recovery time. The aim of this study was to assess current standard of care (SOC)
      for early ICU exercise programs in major burn centers. We designed a survey
      investigating exercise RP on the ICU for burn patients with >30% total burned
      surface area. The survey was composed of 23 questions and submitted
      electronically via SurveyMonkey(r) to six major (pediatric and adult) burn
      centers in Texas and California. All centers responded and reported exercise as
      part of their RP on the ICU. The characteristics of exercises implemented were
      not uniform. All centers reported to perform resistive and aerobic exercises but
      only 83% reported isotonic and isometric exercises. Determination of intensity of
      exercise varied with 50% of centers using patient tolerance and 17% using vital
      signs. Frequency of isotonic, isometric, aerobic, and resistive exercise was
      reported as daily by 80%, 80%, 83%, and 50% of centers, respectively. Duration
      for all types of exercises was extremely variable. Mobilization was used as a
      form of exercise by 100% of burn centers. Our results demonstrate that although
      early RP seem to be integral during burn survivor's ICU stay, no SOC exists.
      Moreover, early RP are inconsistently administered and large variations exist in
      frequency, intensity, duration, and type of exercise. Thus, future prospective
      studies investigating the various components of exercise interventions are needed
      to establish a SOC and determine how and if early exercise benefits the burn
      survivor.

PMID- 29579313
TI  - Sickle cell disease in southwestern Nigeria: assessment of knowledge of primary
      health care workers and available facilities.
AB  - Background: Patients with sickle cell disease (SCD) benefit optimally from
      comprehensive care. In Nigeria, despite the huge burden, involvement of community
      health workers (CHWs) in the management of SCD is poor. Methods: This community
      based study assessed SCD-related knowledge of 182 CHWs from the 46 primary health
      care (PHC) centres in Ilesa, southwestern Nigeria. Available facilities and
      management practices for SCD care at these centres were also evaluated using
      pretested self-administered questionnaires and observational checklists. Results:
      The majority of CHWs (167/182 [91.8%]) knew that SCD is an inheritable blood
      disorder. However, only 32.4% and 26.4% knew that SCD can be diagnosed in the
      prenatal and neonatal periods, respectively. Also 37.4%, 49.5% and 67.6% knew
      about the role of chemoprophylaxis (folic acid/penicillin), adequate fluids and
      malaria prevention, respectively, in SCD care. Overall, 37.9% had good knowledge
      on the nature and care of the disease. Just 2/46 (4.3%) PHC centres treat
      patients with SCD. SCD-targeted nutritional counselling and referral to
      secondary/tertiary hospitals were poor and unorganized. No centre offered SCD
      screening, home visits or recordkeeping. Conclusions: The level of SCD care and
      knowledge of CHWs at PHC centres in southwestern Nigeria of early SCD diagnosis
      and crisis prevention is poor. CHWs should be regularly trained and equipped for
      basic SCD management, including early detection, crisis prevention, prompt
      referral and provision of basic genetic counselling, to dispel associated myths
      and stigma.

PMID- 29579312
TI  - TGMI: an efficient algorithm for identifying pathway regulators through
      evaluation of triple-gene mutual interaction.
AB  - Despite their important roles, the regulators for most metabolic pathways and
      biological processes remain elusive. Presently, the methods for identifying
      metabolic pathway and biological process regulators are intensively sought after.
      We developed a novel algorithm called triple-gene mutual interaction (TGMI) for
      identifying these regulators using high-throughput gene expression data. It first
      calculated the regulatory interactions among triple gene blocks (two pathway
      genes and one transcription factor (TF)), using conditional mutual information,
      and then identifies significantly interacted triple genes using a newly
      identified novel mutual interaction measure (MIM), which was substantiated to
      reflect strengths of regulatory interactions within each triple gene block. The
      TGMI calculated the MIM for each triple gene block and then examined its
      statistical significance using bootstrap. Finally, the frequencies of all TFs
      present in all significantly interacted triple gene blocks were calculated and
      ranked. We showed that the TFs with higher frequencies were usually genuine
      pathway regulators upon evaluating multiple pathways in plants, animals and
      yeast. Comparison of TGMI with several other algorithms demonstrated its higher
      accuracy. Therefore, TGMI will be a valuable tool that can help biologists to
      identify regulators of metabolic pathways and biological processes from the
      exploded high-throughput gene expression data in public repositories.

PMID- 29579314
TI  - Persistent, Consistent, and Extensive: The Trend of Increasing Pain Prevalence in
      Older Americans.
AB  - Objectives: Assess trends in pain prevalence from 1992 to 2014 among older U.S.
      adults and by major population subgroups, and test whether the trends can be
      explained by changes in population composition. Methods: Health and Retirement
      Study data include information on any pain, pain intensity, and limitations in
      usual activities due to pain. Average annual percent change in prevalence is
      calculated for any and for 2 levels of pain-mild/moderate and nonlimiting and
      severe and/or limiting-across demographic and socioeconomic characteristics, and
      for those with and without specific chronic conditions. Generalized linear latent
      and mixed models examine trends adjusting for covariates. Results : Linear and
      extensive increases in pain prevalence occurred across the total population and
      subgroups. The average annual percent increase was in the 2%-3% range depending
      upon age and sex. Increases were consistent across subgroups, persistent over
      time, and not due to changes in population composition. Without increases in
      educational attainment over time, pain prevalence increases would be even higher.
      Discussion: The increases in pain prevalence among older Americans are alarming
      and potentially of epidemic proportions. Population-health research must monitor
      and understand these worrisome trends.

PMID- 29579316
TI  - Obstacles to improving outcomes in the treatment of uveal melanoma.
AB  - The rate of advances in uveal melanoma has not kept pace with the rate of
      advances in cutaneous melanoma. Many patients lack access to or knowledge of
      specialty centers, and integrated multidisciplinary care between ophthalmology,
      radiation oncology, and medical oncology is far from the norm. This treatment
      isolation leads to limited communication about novel clinical trial
      opportunities. Clinical trials themselves are not widely available, and a lack of
      robust funding limits rapid and complete investigations. This review outlines the
      obstacles to success in uveal melanoma management and highlights strategies for
      overcoming these challenges. Cancer 2018;124:2693-2703. (c) 2018 American Cancer
      Society.

PMID- 29579315
TI  - Co-expression of MU and delta opioid receptors by mouse colonic nociceptors.
AB  - BACKGROUND AND PURPOSE: To better understand opioid signalling in visceral
      nociceptors, we examined the expression and selective activation of MU and delta
      opioid receptors by dorsal root ganglia (DRG) neurons innervating the mouse
      colon. EXPERIMENTAL APPROACH: DRG neurons projecting to the colon were identified
      by retrograde tracing. delta receptor-GFP reporter mice, in situ hybridization,
      single-cell RT-PCR and MU receptor-specific antibodies were used to characterize
      expression of MU and delta receptors. Voltage-gated Ca2+ currents and neuronal
      excitability were recorded in small diameter nociceptive neurons (capacitance <30
      pF) by patch clamp and ex vivo single-unit afferent recordings were obtained from
      the colon. KEY RESULTS: In situ hybridization of oprm1 expression in Fast Blue
      labelled DRG neurons was observed in 61% of neurons. MU and delta receptors were
      expressed by 36-46% of colon DRG neurons, and co-expressed by ~25% of neurons. MU
      and delta receptor agonists inhibited Ca2+ currents in DRG, effects blocked by
      opioid antagonists. One or both agonists inhibited action potential firing by
      colonic afferent endings. Incubation of neurons with supernatants from inflamed
      colon segments inhibited Ca2+ currents and neuronal excitability. Antagonists of
      MU, but not delta receptors, inhibited the effects of these supernatant on Ca2+
      currents, whereas both antagonists inhibited their actions on neuronal
      excitability. CONCLUSIONS AND IMPLICATIONS: A significant number of small
      diameter colonic nociceptors co-express MU and delta receptors and are inhibited
      by agonists and endogenous opioids in inflamed tissues. Thus, opioids that act at
      MU or delta receptors, or their heterodimers may be effective in treating
      visceral pain.

PMID- 29579317
TI  - Capture of tobacco use among population-based registries: Findings from 10
      National Program of Cancer Registries states.
AB  - BACKGROUND: Tobacco use data are important when the epidemiology and prognosis of
      tobacco-associated cancers are being defined. Central cancer registries in 10
      National Program of Cancer Registries states pilot-tested the collection of
      standardized tobacco use variables. This study evaluated the capture of tobacco
      use data and examined smoking prevalence among cancer patients. METHODS:
      Participating registries collected data about the use of tobacco-cigarettes,
      other smoked tobacco, and smokeless tobacco-for cases diagnosed during 2011-2013.
      The percentage of cases with known tobacco variable values was calculated, and
      the prevalence of tobacco use was analyzed by the primary cancer site and state.
      RESULTS: Among 1,646,505 incident cancer cases, 51% had known cigarette use data:
      18% were current users, 31% were former users, and 51% reported never using. The
      percentage of cases with a known status for both other smoked tobacco and
      smokeless tobacco was 43%, with 97% and 98% coded as never users, respectively.
      The percent known for cigarette use ranged from 27% to 81% by state and improved
      from 47% in 2011 to 59% in 2013 for all 10 states combined. The percent known for
      cigarette use and the prevalence of ever smoking cigarettes were highest for
      laryngeal cancer and tracheal, lung, and bronchus cancer. CONCLUSIONS: Cancer
      registrars ascertained cigarette use for slightly more than half of all new
      cancer cases, but other tobacco-related fields were less complete. Studies to
      evaluate the validity of specific tobacco-related variables and the ability of
      cancer registries to capture this information from the medical record are needed
      to gauge the usefulness of collecting these variables through cancer surveillance
      systems. Cancer 2018;124:2381-9. (c) 2018 American Cancer Society.

PMID- 29579318
TI  - Increased resource use in men with metastatic prostate cancer does not result in
      improved survival or quality of care at the end of life.
AB  - BACKGROUND: Cancer care and end-of-life (EOL) care contribute substantially to
      health care expenditures. Outside of clinical trials, to our knowledge there
      exists no standardized protocol to monitor disease progression in men with
      metastatic prostate cancer (mPCa). The objective of the current study was to
      evaluate the factors and outcomes associated with increased imaging and serum
      prostate-specific antigen use in men with mPCa. METHODS: Using Surveillance,
      Epidemiology, and End Results-Medicare data from 2004 to 2012, the authors
      identified men diagnosed with mPCa with at least 6 months of follow-up. Extreme
      users were classified as those who had either received prostate-specific antigen
      testing greater than once per month, or who underwent cross-sectional imaging or
      bone scan more frequently than every 2 months over a 6-month period. Associations
      between extreme use and survival outcomes, costs, and quality of care at EOL, as
      measured by timing of hospice referral, frequency of emergency department visits,
      length of stay, and intensive care unit or hospital admissions, were examined.
      RESULTS: Overall, a total of 3026 men with mPCa were identified, 791 of whom
      (26%) were defined as extreme users. Extreme users were more commonly young,
      white/non-Hispanic, married, higher earning, and more educated (P<.001,
      respectively). Extreme use was not associated with improved quality of care at
      EOL. Yearly health care costs after diagnosis were 36.4% higher among extreme
      users (95% confidence interval, 27.4%-45.3%; P<.001). CONCLUSIONS: Increased
      monitoring among men with mPCa significantly increases health care costs, without
      a definitive improvement in survival nor quality of care at EOL noted. Monitoring
      for disease progression outside of clinical trials should be reserved for those
      in whom findings will change management. Cancer 2018;124:2212-9. (c) 2018
      American Cancer Society.

PMID- 29579319
TI  - Biomarkers in colorectal liver metastases.
AB  - BACKGROUND: Despite a 5-year overall survival rate of 58 per cent after liver
      resection for colorectal liver metastases (CLMs), more than half of patients
      develop recurrence, highlighting the need for accurate risk stratification and
      prognostication. Traditional prognostic factors have been superseded by newer
      outcome predictors, including those defined by the molecular origin of the
      primary tumour. METHODS: This review synthesized findings in the literature using
      the PubMed database of articles in the English language published between 1998
      and 2017 on prognostic and predictive biomarkers in patients undergoing resection
      of CLMs. RESULTS: Responses to preoperative chemotherapy define prognosis in
      patients undergoing CLM resection. There are differences by embryological origin
      too. Somatic mutations in the proto-oncogenes KRAS and NRAS are associated with
      positive surgical margins and tumour regrowth after ablation. Other mutations
      (such as BRAF) and co-occurring mutations in RAS/TP53 and APC/PIK3CA have emerged
      as important biomarkers that determine an individual patient's tumour biology and
      may be used to predict outcome after CLM resection. CONCLUSION: Knowledge of
      somatic mutations can guide the use of preoperative therapy, extent of surgical
      margin and selection for ablation alone.

PMID- 29579320
TI  - Randomized clinical trial of platysma muscle suture versus no suture for wound
      closure after thyroid surgery.
AB  - BACKGROUND: Suturing the platysma muscle during wound closure after thyroid
      surgery is frequently described in the literature. There is no prospective
      evidence to support its use or benefit. The aim of this study was to evaluate how
      a platysma muscle suture influences initial postoperative pain following thyroid
      surgery. METHODS: Patients were assigned randomly to receive a platysma suture or
      no platysma suture in this prospective, patient-blinded trial. The duration of
      follow-up was 6 months. The primary endpoint was wound-specific pain 24 h after
      thyroid resection. Secondary endpoints were intraoperative and perioperative
      analgesia requirement, postoperative pain and complications until postoperative
      day 14, and Patient and Observer Scar Assessment Score (POSAS) 6 months after
      surgery. RESULTS: Forty-one patients were randomized to each group. Visual
      analogue scale scores for wound-specific pain were lower in patients without a
      platysma suture 24 h after surgery (mean(s.d.) 3.15(1.46) versus 2.17(1.41) in
      groups with and without suture respectively; P = 0.002). There were no
      differences in the perioperative and postoperative need for analgesics,
      postoperative wound complications or cervical scar cosmesis 6 months after
      surgery (mean(s.d.) POSAS 23.99(9.53) versus 26.51(8.69); P = 0.148). CONCLUSION:
      Omitting the platysma muscle suture after thyroid surgery resulted in less wound
      specific pain initially, with no difference in postoperative wound complications
      or cosmetic results. Registration number: NCT02951000
      (http://www.clinicaltrials.gov).

PMID- 29579321
TI  - Long-term outcome of relapsed acute promyelocytic leukemia treated with oral
      arsenic trioxide-based reinduction and maintenance regimens: A 15-year
      prospective study.
AB  - BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second
      complete remission (CR2), optimal postremission strategies remain undefined.
      METHODS: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the
      management of patients who had APL in CR2 was examined. RESULTS: Seventy-three
      patients with APL in first relapse (R1) were studied. Oral As2 O3 -based
      reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure.
      All patients received oral As2 O3 -based maintenance in CR2. At a median follow
      up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and
      49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans
      retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance
      treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients
      (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35
      patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had
      self-limiting QTc prolongation. The 10-year leukemia-free survival rate was
      56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in
      27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem
      cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30
      months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10
      year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively.
      Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for
      inferior leukemia-free survival. Central nervous system involvement occurred in
      15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy
      was the only significant risk factor for central nervous system involvement.
      CONCLUSIONS: For patients with relapsed APL, As2 O3 remained effective despite
      repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission
      strategy for CR2. Cancer 2018;124:2316-26. (c) 2018 American Cancer Society.

PMID- 29579322
TI  - Multicentre study of laparoscopic or open assessment of the peritoneal cancer
      index (BIG-RENAPE).
AB  - BACKGROUND: The peritoneal cancer index (PCI) is a comparative prognostic factor
      for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to
      determine the PCI in consideration of cytoreductive surgery remains undetermined,
      and this study was designed to compare it with laparotomy. METHODS: A prospective
      multicentre study was conducted for patients with no known CRPM, but at risk of
      peritoneal disease. Surgery began with laparoscopic exploration followed by open
      exploration to determine the PCI. Concordance between laparoscopic and open
      assessment was evaluated for the diagnosis of CRPM and for the PCI. RESULTS:
      Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34
      (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was
      feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52
      per cent (26 of 50). Among the 25 evaluable patients with satisfactory
      laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per
      cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI
      respectively. Where there were discrepancies, it was laparoscopy that
      underestimated the PCI. CONCLUSION: Laparoscopy may underestimate the extent of
      CRPM.

PMID- 29579323
TI  - Identification of potent and selective small molecule inhibitors of the cation
      channel TRPM4.
AB  - BACKGROUND AND PURPOSE: TRPM4 is a calcium-activated non-selective cation channel
      expressed in many tissues and implicated in several diseases, and has not yet
      been validated as a therapeutic target due to the lack of potent and selective
      inhibitors. We sought to discover a novel series of small-molecule inhibitors by
      combining in silico methods and cell-based screening assay, with sub-micromolar
      potency and improved selectivity from previously reported TRPM4 inhibitors.
      EXPERIMENTAL APPROACH: Here, we developed a high throughput screening compatible
      assay to record TRPM4-mediated Na+ influx in cells using a Na+ -sensitive dye and
      used this assay to screen a small set of compounds selected by ligand-based
      virtual screening using previously known weakly active and non-selective TRPM4
      inhibitors as seed molecules. Conventional electrophysiological methods were used
      to validate the potency and selectivity of the hit compounds in HEK293 cells
      overexpressing TRPM4 and in endogenously expressing prostate cancer cell line
      LNCaP. Chemical chaperone property of compound 5 was studied using Western blots
      and electrophysiology experiments. KEY RESULTS: A series of halogenated
      anthranilic amides were identified with TRPM4 inhibitory properties with sub
      micromolar potency and adequate selectivity. We also showed for the first time
      that a naturally occurring variant of TRPM4, which displays loss-of-expression
      and function, is rescued by the most promising compound 5 identified in this
      study. CONCLUSIONS AND IMPLICATIONS: The discovery of compound 5, a potent and
      selective inhibitor of TRPM4 with an additional chemical chaperone feature,
      revealed new opportunities for studying the role of TRPM4 in human diseases and
      developing clinical drug candidates.

PMID- 29579324
TI  - Salvage treatment using carbon ion radiation in patients with locoregionally
      recurrent nasopharyngeal carcinoma: Initial results.
AB  - BACKGROUND: Reirradiation for locoregionally recurrent nasopharyngeal carcinoma
      (NPC) after a definitive dose of radiotherapy (RT) is challenging and usually
      associated with severe toxicities. Intensity-modulated carbon ion RT (IMCT)
      offers physical/biologic advantages over photon-based intensity-modulated RT.
      Herein, the authors report their initial experience of IMCT in previously
      irradiated patients with locoregionally recurrent NPC. METHODS: Patients with
      locoregionally recurrent, poorly differentiated or undifferentiated NPC who
      underwent salvage therapy with IMCT at the Shanghai Proton and Heavy Ion Center
      between May 2015 and August 2017 were included in the current study. The IMCT
      doses were 50 to 66 Gray equivalent (GyE) (2.0-3.0 GyE/daily fraction), delivered
      via raster scanning technology. The 1-year overall survival, disease-specific
      survival, progression-free survival (PFS), local recurrence-free survival,
      regional recurrence-free survival, and distant metastasis-free survival were
      calculated. Univariate and multivariate analyses of PFS were performed to
      identify possible predictive factors. RESULTS: Among the 75 patients included, 4
      patients, 14 patients, 29 patients, and 28 patients, respectively, had recurrent
      American Joint Committee on Cancer stage I, stage II, stage III, and stage IVA/B
      disease. With a median follow-up of 15.4 months (range, 2.6-29.7 months), the 1
      year overall survival, disease-specific survival, PFS, local recurrence-free
      survival, regional recurrence-free survival, and distant metastasis-free survival
      rates were 98.1%, 98.1%, 82.2%, 86.6%, 97.9%, and 96.2%, respectively. A higher
      fraction size of 3 GyE (vs <3 GyE) or a higher biological equivalent dose
      significantly improved the PFS rate on univariate analysis, but not on
      multivariate analysis. No patient developed acute toxicity of grade >=2 during
      IMCT. Late treatment-induced severe (grade 3 or 4) toxicities were infrequent,
      but included mucosal necrosis (9.3%), xerostomia (1.3%), and temporal lobe
      necrosis (1.3%). CONCLUSIONS: This initial experience in the first 75 patients
      with locoregionally recurrent NPC was encouraging. Carbon ion RT could provide
      promising survival rates with infrequent severe toxicities for patients with
      locoregionally recurrent NPC. Cancer 2018;124:2427-37. (c) 2018 The Authors.
      Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

PMID- 29579326
TI  - Follow-up after endovascular aortic aneurysm repair can be stratified based on
      first postoperative imaging.
AB  - BACKGROUND: Lifelong postoperative surveillance is recommended following
      endovascular aneurysm repair (EVAR). Although the purpose is to prevent and/or
      identify complications early, it also results in increased cost and workload.
      This study was designed to examine whether it may be possible to identify
      patients at low risk of complications based on their first postoperative CT
      angiogram (CTA). METHODS: All patients undergoing EVAR in two Swedish centres
      between 2001 and 2012 were identified retrospectively and categorized based on
      the first postoperative CTA as at low risk (proximal and distal sealing zone at
      least 10 mm and no endoleak) or high risk (sealing zone less than 10 mm and/or
      presence of any endoleak) of complications. RESULTS: Some 326 patients (273 men)
      with a CTA performed less than 1 year after EVAR were included (low risk 212,
      65.0 per cent; high risk 114, 35.0 per cent). There was no difference between the
      groups in terms of sex, age, co-morbidities, abdominal aortic aneurysm (AAA)
      diameter, preoperative AAA neck anatomy, stent-graft type or duration of follow
      up (mean(s.d.) 4.8(3.2) years). Five-year freedom from AAA-related adverse events
      was 97.1 and 47.7 per cent in the low- and high-risk groups respectively (P <
      0.001). The corresponding freedom from AAA-related reintervention was 96.2 and
      54.1 per cent (P < 0.001). The method had a sensitivity of 88.3 per cent,
      specificity of 77.0 per cent and negative predictive value of 96.6 per cent to
      detect AAA-related adverse events. The number of surveillance imaging per AAA
      related adverse event was 168 versus 11 for the low-risk versus high-risk group.
      CONCLUSION: Two-thirds of patients undergoing EVAR have an adequate seal and no
      endoleak on the first postoperative CTA, and a very low risk of AAA-related
      events up to 5 years. Less vigilant follow-up after EVAR may be considered for
      these patients.

PMID- 29579325
TI  - A phase 2 study of the PARP inhibitor veliparib plus temozolomide in patients
      with heavily pretreated metastatic colorectal cancer.
AB  - BACKGROUND: Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors such
      as veliparib are potent sensitizing agents and have been safely combined with DNA
      damaging agents such as temozolomide. The sensitizing effects of PARP inhibitors
      are magnified when cells harbor DNA repair defects. METHODS: A single-arm, open
      label, phase 2 study was performed to investigate the disease control rate (DCR)
      after 2 cycles of veliparib plus temozolomide in patients with metastatic
      colorectal cancer (mCRC) refractory to all standard therapies. Fifty patients
      received temozolomide (150 mg/m2 /d) on days 1 to 5 and veliparib (40 mg twice
      daily) on days 1 to 7 of each 28-day cycle. Another 5 patients with mismatch
      repair-deficient (dMMR) tumors were also enrolled. Twenty additional patients
      were then treated with temozolomide at 200 mg/m2 /d. Archived tumor specimens
      were used for immunohistochemistry to assess mismatch repair, phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN), and O(6)-methylguanine-DNA
      methyltransferase (MGMT) protein expression levels. RESULTS: The combination was
      well tolerated, although some patients required dose reductions for
      myelosuppression. The primary endpoint was successfully met with a DCR of 24% and
      2 confirmed partial responses. The median progression-free survival was 1.8
      months, and the median overall survival was 6.6 months. PTEN protein expression
      and MGMT protein expression were not predictors of DCR. There was also a
      suggestion of worse outcomes for patients with dMMR tumors. CONCLUSIONS: In this
      heavily pretreated mCRC population, a combination of veliparib and temozolomide
      was well tolerated with temozolomide doses up to 200 mg/m2 /d, and it was
      clinically active. PARP inhibitor-based therapy merits further exploration in
      patients with mCRC. Cancer 2018;124:2337-46. (c) 2018 American Cancer Society.

PMID- 29579327
TI  - Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence
      in the FACS randomized clinical trial.
AB  - BACKGROUND: Most guidelines recommend that patients who have undergone curative
      resection for primary colorectal cancer are followed up for 5 years with regular
      blood carcinoembryonic antigen (CEA) tests to trigger further investigation for
      recurrence. However, CEA may miss recurrences, or patients may have false alarms
      and undergo unnecessary investigation. METHODS: The diagnostic accuracy of trends
      in CEA measurements for recurrent colorectal cancer, taken as part of the FACS
      (Follow-up After Colorectal Surgery) trial (2003-2014), were analysed.
      Investigation to detect recurrence was triggered by clinical symptoms, scheduled
      CT or colonoscopy, or a CEA level of at least 7 MUg/l above baseline. Time
      dependent receiver operating characteristic (ROC) curve analysis was used to
      compare the diagnostic accuracy of CEA trends with single measurements. CEA
      trends were estimated using linear regression. RESULTS: The area under the ROC
      curve (AUC) for CEA trend was at least 0.820 across all 5 years of follow-up. In
      comparison, the AUCs for single measurements ranged from 0.623 to 0.749.
      Improvement was most marked at the end of the first year of follow-up, with the
      AUC increasing from 0.623 (95 per cent c.i. 0.509 to 0.736) to 0.880 (0.814 to
      0.947). However, no individual trend threshold achieved a sensitivity above 70
      per cent (30 per cent missed recurrences). CONCLUSION: Interpreting trends in CEA
      measurements instead of single CEA test results improves diagnostic accuracy for
      recurrence, but not sufficiently to warrant it being used as a single
      surveillance strategy to trigger further investigation. In the absence of a more
      accurate biomarker, monitoring trends in CEA should be combined with clinical,
      endoscopic and imaging surveillance for improved accuracy.

PMID- 29579329
TI  - Prediction of morbidity following cytoreductive surgery for metastatic
      gastrointestinal stromal tumour in patients on tyrosine kinase inhibitor therapy.
AB  - BACKGROUND: Although cytoreductive surgery has been shown to be beneficial in
      carefully selected patients with metastatic gastrointestinal stromal tumours
      (GISTs) treated with tyrosine kinase inhibitors (TKIs), factors predictive of
      postoperative morbidity have not been investigated previously. METHODS: A
      surgical complexity score for GIST metastasectomy (GM-SCS) composed of patient
      related and surgical factors was assigned retrospectively to patients with
      metastatic GIST treated with TKI therapy and surgery at two institutions between
      2002 and 2014. The ability of clinicopathological factors and GM-SCS to predict
      postoperative morbidity was assessed by means of a multivariable logistic
      regression model. Postoperative complications were categorized using the Clavien
      Dindo classification. RESULTS: Some 400 operations on 323 patients with
      metastatic GIST on TKIs were included. Complications were observed following 110
      operations (27.5 per cent) including 70 major complications (grade III-V) (17.5
      per cent of 400 operations). Patients were divided into low (5 points or less;
      100 patients, 25.0 per cent), intermediate (6-9 points; 191, 47.8 per cent) and
      high (at least 10 points; 109, 27.3 per cent) complexity scoring groups based on
      the GM-SCS. An intermediate (odds ratio (OR) 2.88; P = 0.008) and high (OR 5.40;
      P < 0.001) GM-SCS were independent predictors of overall complications, whereas
      only a high GM-SCS was independently predictive of a major complication (OR 3.65;
      P = 0.018). Metastatic mitotic index was also an independent predictor of overall
      complications (OR 2.55; P = 0.047). GM-SCS did not predict progression-free or
      overall survival. CONCLUSION: A gastrointestinal stromal tumour metastastectomy
      surgical complexity score can predict morbidity, which may help in preoperative
      risk stratification and optimal treatment planning.

PMID- 29579328
TI  - Complex karyotype in patients with mantle cell lymphoma predicts inferior
      survival and poor response to intensive induction therapy.
AB  - BACKGROUND: Risk stratification of newly diagnosed patients with mantle cell
      lymphoma (MCL) primarily is based on the MCL International Prognostic Index
      (MIPI) and Ki-67 proliferative index. Single-center studies have reported
      inferior outcomes in patients with a complex karyotype (CK), but this remains an
      area of controversy. METHODS: The authors retrospectively reviewed 483 patients
      from 5 academic centers in the United States and described the effect of a CK on
      survival outcomes in individuals with MCL. RESULTS: A CK was found to be
      associated with inferior overall survival (OS) (4.5 vs 11.6 years; P<.01) and
      progression-free survival (PFS) (1.9 vs 4.4 years; P<.01). In patients who
      underwent high-intensity induction followed by autologous stem cell
      transplantation (ASCT) in first remission, a CK was associated with poor OS (5.1
      vs 11.6 years; P = .04) and PFS (3.6 vs 7.8 years; P<.01). Among patients with a
      CK, high-intensity induction had no effect on OS (4.5 vs 3.8 years; P = .77) nor
      PFS (2.3 vs 1.5 years; P = .46). Similarly, ASCT in first remission did not
      improve PFS (3.5 vs 1.2 years; P = .12) nor OS (5.1 vs 4.0 years; P = .27). On
      multivariable analyses with Ki-67 and MIPI, only CK was found to be predictive of
      OS (hazard ratio [HR], 1.98; 95% confidence interval [95% CI], 1.12-3.49 [P =
      .02]), whereas both CK (HR, 1.91; 95% CI, 1.17-3.12 [P = .01]) and Ki-67 >30%
      (HR, 1.86; 95% CI, 1.06-3.28 [P = .03]) were associated with inferior PFS.
      Multivariable analysis did not identify any specific cytogenetic abnormalities
      associated with inferior survival. CONCLUSIONS: CK appears to be independently
      associated with inferior outcomes in patients with MCL regardless of the
      intensity of induction therapy and receipt of ASCT. Cytogenetics should be
      incorporated into the workup of a new diagnosis of MCL and novel therapeutic
      approaches should be investigated for patients with CK. Cancer 2018;124:2306-15.
      (c) 2018 American Cancer Society.

PMID- 29579330
TI  - Impact of the posttransplant lymphoproliferative disorder subtype on survival.
AB  - BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life
      threatening complication of solid organ transplantation. Histologic heterogeneity
      and a lack of treatment standards have made evaluating clinical outcomes in
      specific patient populations difficult. This systematic literature review
      investigated the impact of the PTLD histologic subtype on survival in a large
      data set. METHODS: Case series were identified on PubMed with the search terms
      post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ
      transplantation, with additional publications identified through reference lists.
      The patient characteristics, immunosuppressive regimen, treatment, survival, and
      follow-up time for 306 cases were extracted from 94 articles, and these cases
      were combined with 11 cases from Emory University Hospital. Patients with a
      recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox
      proportional hazards regression analyses identified predictors of overall
      survival (OS) for each subtype and B-cell subgroup. RESULTS: OS differed
      significantly between monomorphic T-cell neoplasms (median, 9 months) and
      polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median
      OS was not reached (P = .0001). Significant differences in OS among B subgroups
      were not detected, but there was a trend toward decreased survival for patients
      with Burkitt-type PTLD. Kidney transplantation and a reduction of
      immunosuppression were associated with increased OS for patients with B-cell
      neoplasms in a multivariate analysis. Immunosuppression with azathioprine was
      associated with decreased OS for patients with T-cell neoplasms, whereas
      radiotherapy was associated with improved OS for patients with that subtype.
      CONCLUSIONS: The histologic subtype represents an important prognostic factor in
      PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower
      survival for certain subsets of patients with B-cell PTLD should be explored
      further and suggests the need for subtype-specific therapies to improve outcomes.
      Cancer 2018;124:2327-36. (c) 2018 American Cancer Society.

PMID- 29579331
TI  - Erlotinib in the treatment of recurrent or metastatic cutaneous squamous cell
      carcinoma: A single-arm phase 2 clinical trial.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a very common malignancy
      in which most patients present with localized disease. Recurrent and metastatic
      disease is rare, and there is no standard therapy. These tumors frequently
      overexpress the epidermal growth factor receptor (EGFR). We conducted a phase 2
      trial to determine the response rate to therapy with erlotinib, an EGFR tyrosine
      kinase inhibitor, in patients with locoregionally recurrent or metastatic CSCC
      that was not amenable to curative treatment (NCT01198028). METHODS: Eligible
      patients had CSCC not amenable to curative intent therapy. Patients who had
      previously received anti-EGFR targeted therapy were excluded. All patients
      received oral therapy with erlotinib 150 mg daily. Response was assessed every 8
      weeks, and treatment continued until progression, unacceptable toxicity, or
      withdrawal of consent. The primary endpoint was overall response rate according
      to RECIST 1.1 criteria. RESULTS: A total of 39 patients received treatment during
      the trial; 29 of these patients were evaluable for response. The overall response
      rate was 10% (3/29); all responses were partial responses. The disease control
      rate (partial response + stable disease) was 72% (21/29). The median progression
      free survival was 4.7 months (95% confidence interval, 3.5-6.2 months); the
      median overall survival was 13 months (95% confidence interval, 8.4-20.5 months).
      No unexpected toxicities were seen. CONCLUSION: Erlotinib therapy was feasible
      for most patients with incurable CSCC and was associated with expected
      toxicities. However, only a modest response rate of 10% was observed. Further
      study of EGFR tyrosine kinase inhibitors in this patient population is not
      warranted. Cancer 2018;124:2169-73. (c) 2018 American Cancer Society.

PMID- 29579332
TI  - Late therapeutic intervention with a respiratory syncytial virus L-protein
      polymerase inhibitor, PC786, on respiratory syncytial virus infection in human
      airway epithelium.
AB  - BACKGROUND AND PURPOSE: Effective anti-respiratory syncytial virus (RSV) agents
      are still not available for clinical use. Current major targets are virus surface
      proteins, such as a fusion protein involved in viral entry, but agents effective
      after RSV infection is established are required. Here we have investigated the
      effects of late therapeutic intervention with a novel inhaled RSV polymerase
      inhibitor, PC786, on RSV infection in human airway epithelium. EXPERIMENTAL
      APPROACH: Air liquid interface-cultured bronchial or small airway epithelium was
      infected with RSVA2. PC786 was applied apically or basolaterally once daily
      following peak virus load on Day 3 post inoculation. Apical wash was collected
      daily for determination of viral burden by PCR and plaque assay (primary
      endpoints) and biomarker analyses. The effects were compared with those of ALS
      8112, an anti-RSV nucleoside analogue, and GS-5806, a fusion-protein inhibitor,
      which were treated basolaterally. KEY RESULTS: Late intervention with GS-5806 did
      not show significant anti-viral effects, but PC786 produced potent, concentration
      dependent inhibition of viral replication with viral load falling below
      detectable limits 3 days after treatment commenced in airway epithelium. These
      effects were superior to those of ALS-8112. PC786 showed inhibitory activities
      against RSV-induced increases of CCL5, IL-6, double-strand DNA and mucin. The
      effects of PC786 were also confirmed in small airway epithelium. CONCLUSION AND
      IMPLICATIONS: Late therapeutic intervention with the RSV polymerase inhibitor,
      PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786
      demonstrates the potential to be an effective therapeutic agent to treat active
      RSV infection.

PMID- 29579333
TI  - Initial experience with purely laparoscopic living-donor right hepatectomy.
AB  - BACKGROUND: There may be concerns about purely laparoscopic donor right
      hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when
      performed by surgeons accustomed to open surgery. This study aimed to describe
      technical tips and pitfalls in PLDRH. METHODS: Data from donors who underwent
      PLDRH at Seoul National University Hospital between December 2015 and July 2017
      were analysed retrospectively. Endpoints analysed included intraoperative events
      and postoperative complications. All operations were performed by a single
      surgeon with considerable experience in open living donor hepatectomy. RESULTS: A
      total of 26 donors underwent purely laparoscopic right hepatectomy in the study
      interval. No donor required transfusion during surgery, whereas two underwent
      reoperation. In two donors, the dissection plane at the right upper deep portion
      of the midplane was not correct. One donor experienced portal vein injury during
      caudate lobe transection, and one developed remnant left hepatic duct stenosis.
      One donor experienced remnant portal vein angulation owing to a different
      approach angle, and one experienced arterial damage associated with the use of a
      laparoscopic energy device. One donor had postoperative bleeding due to masking
      of potential bleeding foci owing to intra-abdominal pressure during laparoscopy.
      Two donors experienced right liver surface damage caused by a xiphoid trocar.
      CONCLUSION: Purely laparoscopic donor hepatectomy differs from open donor
      hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in
      open donor hepatectomy must gain adequate experience in laparoscopic liver
      surgery and make adjustments when performing PLDRH.

PMID- 29579334
TI  - Long-term safety and survival with gefitinib in select patients with advanced non
      small cell lung cancer: Results from the US IRESSA Clinical Access Program
      (ICAP).
AB  - BACKGROUND: This is the first report of long-term (>10 years) safety,
      tolerability, and survival data on patients with non-small cell lung cancer
      (NSCLC) who received treatment with gefitinib, an epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitor. METHODS: Patients with advanced NSCLC
      (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to
      January 2013) and had previously obtained a clinical benefit from gefitinib
      therapy (including patients who had received gefitinib since 2001) were analyzed
      for adverse events (AEs). A subset of patients (n = 79) underwent retrospective
      chart review to capture demographic, safety, and survival data. RESULTS: Seventy
      five of 191 patients (39%) remained on long-term gefitinib therapy as of
      September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%),
      the majority of which were attributed to underlying disease or comorbidities;
      only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib
      related. In the retrospective chart review cohort, 70% of patients were women;
      58% were former smokers, and 30% were never-smokers; 56% were diagnosed with
      adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR
      mutational status was tested in only 17 patients (22%), it was assumed that most
      tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was
      11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year
      survival rates of 86% and 59%, respectively, from the initiation of therapy.
      CONCLUSIONS: A subset of long-term NSCLC survivors who were receiving gefitinib
      had an excellent long-term safety profile. Although it is assumed that most of
      these patients' tumors harbor EGFR mutations, molecular studies of available
      tumor specimens are planned to uncover the features that predict long-term
      survival. Cancer 2018;124:2407-14. (c) 2018 American Cancer Society.

PMID- 29579335
TI  - Cancer survival among Alaska Native people.
AB  - BACKGROUND: Recent cancer survival trends among American Indian and Alaska Native
      (AN) people are not well understood; survival has not been reported among AN
      people since 2001. METHODS: This study examined cause-specific survival among AN
      cancer patients for lung, colorectal, female breast, prostate, and kidney
      cancers. It evaluated whether survival differed between cancers diagnosed in 1992
      2002 (the earlier period) and cancers diagnosed in 2003-2013 (the later period)
      and by the age at diagnosis (<65 vs >=65 years), stage at diagnosis (local or
      regional/distant/unknown), and sex. Kaplan-Meier and Cox proportional hazards
      models were used to estimate univariate and multivariate-adjusted cause-specific
      survival for each cancer. RESULTS: An improvement was observed in 5-year survival
      over time from lung cancer (hazard ratio [HR] for the later period vs the earlier
      period, 0.83; 95% confidence interval [CI], 0.72-0.97), and a marginally
      nonsignificant improvement was observed for colorectal cancer (HR, 0.81; 95% CI,
      0.66-1.01). Site-specific differences in survival were observed by age and stage
      at diagnosis. CONCLUSIONS: This study presents the first data on cancer survival
      among AN people in almost 2 decades. During this time, AN people have experienced
      improvements in survival from lung and colorectal cancers. The reasons for these
      improvements may include increased access to care (including screening) as well
      as improvements in treatment. Improving cancer survival should be a priority for
      reducing the burden of cancer among AN people and eliminating cancer disparities.
      Cancer 2018;124:2570-7. (c) 2018 American Cancer Society.

PMID- 29579337
TI  - Power and sample size calculation incorporating misspecifications of the variance
      function in comparative clinical trials with over-dispersed count data.
AB  - Over-dispersed count data are frequently observed in clinical trials where the
      primary endpoint is occurrence of clinical events. Sample sizes of comparative
      clinical trials with these data are typically calculated under negative binomial
      models or quasi-Poisson models with specified variance functions, or under the
      assumption that the specified "working" variance functions are correctly
      specified. In this article, we propose a sample size formula anticipating
      misspecifications of the working variance function. We derived a method based on
      the asymptotic distribution of a Wald test statistic with a sandwich-type robust
      variance estimator under quasi-Poisson models. Under misspecifications of the
      working variance function, the asymptotic variance of the estimator of the
      treatment effect is expressed as a form involving both true and working variance
      functions. Our sample size formula includes several existing formulas as special
      cases when the working variance function is correctly specified as the true
      variance function. We also consider a sensitivity analysis for possible
      misspecifications of the "true" variance function when estimating sample sizes
      using our formula. A simulation study demonstrated the adequacy of our formulas
      in finite sample size settings. An application to a clinical trial to evaluate
      the treatment effect on prevention of COPD exacerbation is provided.

PMID- 29579336
TI  - Risk profile analysis and complications after surgery for autoimmune thyroid
      disease.
AB  - BACKGROUND: Surgical approaches to autoimmune thyroid disease are currently
      hampered by concerns over postoperative complications. Risk profiles and
      incidences of postoperative complications have not been investigated
      systematically, and studies with sufficient power to show valid data have not
      been performed. METHODS: A prospective multicentre European study was conducted
      between July 2010 and December 2012. Questionnaires were used to collect data
      prospectively on patients who had surgery for autoimmune thyroid disease and the
      findings were compared with those of patients undergoing surgery for multinodular
      goitre. Logistic regression analysis was used to evaluate risk factors for
      thyroid surgery-specific complications, transient and permanent recurrent
      laryngeal nerve (RLN) palsy and hypoparathyroidism. RESULTS: Data were available
      for 22 011 patients, of whom 18 955 were eligible for analysis (2488 who had
      surgery for autoimmune thyroid disease and 16 467 for multinodular goitre).
      Surgery for multinodular goitre and that for autoimmune thyroid disease did not
      differ significantly with regard to general complications. With regard to thyroid
      surgery-specific complications, the rate of temporary and permanent vocal cord
      palsy ranged from 2.7 to 6.7 per cent (P = 0.623) and from 0.0 to 1.4 per cent (P
      = 0.600) respectively, whereas the range for temporary and permanent
      hypoparathyroidism was 12.9 to 20.0 per cent (P < 0.001) and 0.0 to 7.0 per cent
      (P < 0.001) respectively. In logistic regression analysis of transient and
      permanent vocal cord palsy, autoimmune thyroid disease was not an independent
      risk factor. Autoimmune thyroid disease, extent of thyroid resection, number of
      identified parathyroid glands and no autotransplantation were identified as
      independent risk factors for both transient and permanent hypoparathyroidism.
      CONCLUSION: Surgery for autoimmune thyroid disease is safe in comparison with
      surgery for multinodular goitre in terms of general complications and RLN palsy.
      To avoid the increased risk of postoperative hypoparathyroidism, special
      attention needs to be paid to the parathyroid glands.

PMID- 29579338
TI  - Development of CNS metastases and survival in patients with inflammatory breast
      cancer.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is associated with a poor prognosis
      and high risk of central nervous system (CNS) metastases. METHODS: We
      retrospectively reviewed stage III-IBC patients compared with noninflammatory
      invasive ductal carcinoma (NI-IDC) patients treated between January 1, 1984, and
      December 31, 2011, who began primary treatment within 1 year of diagnosis and had
      been followed up for at least 1 year before the development of CNS metastasis or
      death. Cumulative CNS metastasis incidence and post-CNS metastasis overall
      survival (OS) estimates were computed. Multivariable Cox proportional hazard
      models explored factors for post-CNS metastasis survival. RESULTS: A total of
      2323 patients were identified (589-IBC/1734-NI-IDC). Eighty-one IBC patients
      developed CNS metastasis, versus 154 NI-IDC patients. The 2-, 5-, and 10-year
      cumulative CNS metastasis incidence rates in IBC and NI-IDC were 9.8%, 15.8%,
      17.4% and 6.5%, 10.1%, and 12.7%, respectively. This was significantly different
      between IBC and NI-IDC patients (P = .0037). Multicovariate competing risk
      regression models in IBC and NI-IDC patients showed no statistically significant
      associations with the risk of developing CNS metastasis, except neoadjuvant
      taxane use in NI-IDC patients (hazard ratio, 0.45; 95% confidence interval, 0.24
      0.83; P = .011). The median follow-up was 7.2 years, and the median post-CNS
      metastasis OS was not significantly different between IBC (7.6 months) and NI-IDC
      (5.6 months) patients. One hundred ninety patients with CNS metastasis died. HER2
      positive patients had better OS, with a median 14.1 versus 4.3 months (P <
      .0001). Age >50 years (P = .012) but not IBC status was a significant predictor
      of post-CNS metastasis survival. CONCLUSION: IBC patients demonstrated higher CNS
      metastasis incidence rates but OS following CNS metastases is similar in both
      groups. HER2 status and age may play prognostic roles. Cancer 2018;124:2299-305.
      (c) 2018 American Cancer Society.

PMID- 29579339
TI  - Mature results of a prospective study of deintensified chemoradiotherapy for low
      risk human papillomavirus-associated oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The purpose of the current study was to determine quality of life and
      tumor control from a prospective phase 2 clinical trial evaluating deintensified
      chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated
      oropharyngeal squamous cell carcinoma. METHODS: Patients with T0-T3, N0-N2c, M0,
      p16-positive disease and a minimal smoking history were treated with 60 grays of
      intensity-modulated radiotherapy with concurrent weekly intravenous cisplatin (30
      mg/m2 ). The primary study endpoint was the pathologic complete response rate
      based on biopsy of the primary site and dissection of pretreatment positive lymph
      node regions. The pathologic complete response rate as previously reported was
      86%. Herein, the authors report secondary endpoint measures of local control,
      regional control, cause-specific survival, distant metastasis-free survival, and
      overall survival, and patient-reported outcomes (European Organization for
      Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ
      C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for
      Adverse Events [PRO-CTCAE]). RESULTS: A total of 44 patients enrolled with a
      median follow-up of 36 months (88% with >=2 years). The 3-year local control,
      regional control, cause-specific survival, distant metastasis-free survival, and
      overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The
      mean before and 3-year after EORTC QOL scores were: global: 80 of 78; swallowing:
      11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3
      year after PRO-CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of
      1.4. Approximately 39% of patients required a feeding tube (median duration, 15
      weeks; none were permanent). There were no >=grade 3 late adverse events
      reported. CONCLUSIONS: For patients with favorable-risk human papillomavirus
      associated oropharyngeal squamous cell carcinoma, a substantially decreased
      intensity of therapy with 60 grays of intensity-modulated radiotherapy and weekly
      low-dose cisplatin produced better preservation of quality of life compared with
      standard therapies while maintaining excellent 3-year tumor control and survival.
      Cancer 2018;124:2347-54. (c) 2018 American Cancer Society.

PMID- 29579340
TI  - Association of externalizing religious and spiritual beliefs on stage of colon
      cancer diagnosis among black and white multicenter urban patient populations.
AB  - BACKGROUND: This study explores whether externalizing religious and spiritual
      beliefs is associated with advanced-stage colon cancer at initial oncology
      presentation and whether this association is stronger for blacks than for whites.
      METHODS: Patients who had newly diagnosed, invasive colon cancer were recruited
      at 9 sites in the Chicago metropolitan area. Eligible patients were non-Hispanic
      white or black, ages 30 to 79 years, and diagnosed with a primary invasive colon
      cancer. Patients were interviewed on prior screening and diagnosis. Social and
      attitudinal constructs were measured, including the God Locus of Health Control
      (GLHC) and Religious Problem Solving. The final response rate was 52% and
      included 407 patients. RESULTS: The median age was 59 years (range, 30-79 years),
      and 51% of participants were black. Cancer stage was available for 389 (96%)
      patients and was divided between late stage (stages III-IV; 60%) and early stage
      (stages I-II; 40%). Multivariate analysis indicated that patients in the highest
      tertile of scores on the GLHC were more likely have an advanced stage of disease
      at presentation (odds ratio, 2.14; 95% confidence interval, 1.00-4.59; P = .05)
      compared with those in the lowest tertile. No significant interaction was
      identified between race and GLHC scores for stage at presentation (P = .78).
      CONCLUSIONS: In a large sample of black and white individuals across diverse
      health care systems, higher scores on the GLHC predicted late disease stage at
      presentation. Although blacks had significantly higher GLHC scores, race was not
      associated with stage at presentation, nor was the association between GLHC and
      stage limited to blacks. Further work is needed to better understand this
      association and to develop interventions to better connect the religious and
      health care spheres. Cancer 2018;124:2578-87. (c) 2018 American Cancer Society.

PMID- 29579341
TI  - Bayesian nonparametric generative models for causal inference with missing at
      random covariates.
AB  - We propose a general Bayesian nonparametric (BNP) approach to causal inference in
      the point treatment setting. The joint distribution of the observed data
      (outcome, treatment, and confounders) is modeled using an enriched Dirichlet
      process. The combination of the observed data model and causal assumptions allows
      us to identify any type of causal effect-differences, ratios, or quantile
      effects, either marginally or for subpopulations of interest. The proposed BNP
      model is well-suited for causal inference problems, as it does not require
      parametric assumptions about the distribution of confounders and naturally leads
      to a computationally efficient Gibbs sampling algorithm. By flexibly modeling the
      joint distribution, we are also able to impute (via data augmentation) values for
      missing covariates within the algorithm under an assumption of ignorable
      missingness, obviating the need to create separate imputed data sets. This
      approach for imputing the missing covariates has the additional advantage of
      guaranteeing congeniality between the imputation model and the analysis model,
      and because we use a BNP approach, parametric models are avoided for imputation.
      The performance of the method is assessed using simulation studies. The method is
      applied to data from a cohort study of human immunodeficiency virus/hepatitis C
      virus co-infected patients.

PMID- 29579342
TI  - Cost considerations for systemic therapy for patients with advanced genitourinary
      malignancies.
AB  - The rising cost of health care in the United States has been the focus of intense
      debate within the medical, legal, and legislative arenas, with the cost of cancer
      care representing an important component. Cost effectiveness is not always easy
      to define, and there is no standard metric in assessing this measure related to
      cancer therapies. Significant controversy surrounds exactly what is the
      appropriate cost per added year of life. This review examines cost,
      effectiveness, and comparative cost effectiveness of novel systemic therapies for
      patients with urologic malignancies. Cancer 2018;124:2897-905. (c) 2018 American
      Cancer Society.

PMID- 29579343
TI  - Separation of superparamagnetic magnetite nanoparticles by capillary zone
      electrophoresis using non-complexing and complexing electrolyte anions and
      tetramethylammonium as dispersing additive.
AB  - Separations of bare superparamagnetic magnetite nanoparticles (BSPMNPs, approx.
      11 nm diameter) was performed using non-complexing (nitrate) and complexing
      (chloride, citrate and phosphate) electrolyte ions with additions of
      tetramethylammonium hydroxide (TMAOH), which is commonly applied to control the
      synthesis of stable iron oxides. The use of TMAOH as a background electrolyte
      (BGE) additive for capillary electrophoresis (CE) separations provided for the
      first time electropherograms of BSPMNPs exhibiting symmetrical and highly
      reproducible peaks, free of spurious spikes characteristic of nanoparticle
      clusters. Consequently, accurate determination of the electrophoretic effective
      mobility of BSPMNPs was possible, yielding a value of -3.345E-08 m2 V-1 s-1
      (relative standard deviation (RSD) of 0.500%). The obtained mobilities of BSPMNPs
      in the presence of various electrolyte ions show that the degree of complexation
      with the surface of BSPMNPs follows the order chloride < citrate < phosphate,
      correlating with the stabilities of Fe(III) complexes with the respective anions.
      Finally, bare and carboxylated iron oxide nanoparticles were successfully
      separated in only 10 min using 10 mM Tris-nitrate containing 20 mM of TMAOH as
      electrolyte. Our findings show that simple and rapid CE experiments are an
      excellent tool to characterise and monitor properties and interactions of iron
      oxide nanoparticles with other molecules for surface modification purposes.

PMID- 29579344
TI  - A Novel Cell Fixation Method that Greatly Enhances Protein Identification in
      Microproteomic Studies Using Laser Capture Microdissection and Mass Spectrometry.
AB  - Microproteomic studies have improved our knowledge of cell biology. Yet, with
      mass spectrometry (MS) analysis, accuracy can be lost for protein identification
      and quantification when using heterogeneous samples. Laser capture
      microdissection (LCM) allows for the enrichment of specific subsets of cells to
      study their proteome; however, sample fixation is necessary. Unfortunately,
      fixation hampers MS results due to protein cross-linking. The aim of this study
      was to identify both a fixation protocol and an extraction method that returns
      the best yield of proteins for downstream MS analysis, while preserving cellular
      structures. We compared glutaraldehyde (GLU), a common fixative to preserve
      cells, to dithiobispropionimidate (DTBP), a cleavable cross-linker. Our DTBP
      fixation/extraction protocol greatly increased the protein recovery. In fact,
      while 1000 GLU fixed cells returned only 159 unique protein hits, from 1464
      unique peptides of 1994 unique collected spectra, 1000 DTBP fixed cells resulted
      in 567 unique collected protein hits, from 7542 unique peptides, of 10,401 unique
      collected spectra. That is, a 3.57-fold increase in protein hits, 5.15-fold
      increase in unique peptides, and a 5.22-fold increase in unique collected
      spectra. Overall, the novel protocol introduced here allows for a very efficient
      protein recovery and good sample quality for MS after sample collection using
      LCM.

PMID- 29579345
TI  - The effects of prebiotic supplementation on weight gain, diarrhoea, constipation,
      fever and respiratory tract infections in the first year of life.
AB  - AIM: This study was conducted to evaluate the effect of prebiotics on some common
      clinical ailments in healthy term infants. METHODS: Sixty healthy-term, breastfed
      (BF) infants were included. Along with these infants, 120 healthy-term formula
      fed infants were randomly assigned to either the prebiotic formula (PF, n = 60)
      or regular formula (RF, n = 60) groups. Ready-to-use prebiotic-supplemented
      formula containing galacto-oligosaccharides and polydextrose (ratio 1:1) was
      used. RESULTS: At 2 months of age, PF infants demonstrated significantly higher
      weight gain than BF and RF. At 6 months of age, bodyweight was significantly
      higher in the RF group compared to BF and PF groups (P < 0.05). Similar results
      were seen at 8, 10 and 12 months of age. At 10 months of age, the duration of
      diarrhoea was significantly shorter in PF-fed compared to the RF (P = 0.03)
      group. A significant difference was found between PF and RF (P < 0.0001) and BF
      and RF groups (P = 0.002) for diarrhoea duration. Means of constipation episodes
      per year were 0.03 +/- 0.18, 0.433 +/- 0.77 and 0.1 +/- 0.30 for the BF, RF and
      PF groups, respectively, with significant difference found between BF and RF (P =
      0.006) and PF and RF (P = 0.02). The means of episodes of respiratory tract
      infections per year for BF, RF and PF groups were 1 +/- 0.69, 1.6 +/- 0.88 and 1
      +/- 0.58, respectively (P = 0.01). CONCLUSION: Prebiotic-supplemented and regular
      formula were similar to breast milk regarding prophylactic effects for diarrhoea,
      constipation and respiratory tract infections in the first year of life.
      Prebiotic-supplemented formula may be an appropriate substitution for breast milk
      when breast milk in unavailable.

PMID- 29579347
TI  - Two-fold Bioorthogonal Derivatization by Different Formylglycine-Generating
      Enzymes.
AB  - Formylglycine-generating enzymes are of increasing interest in the field of
      bioconjugation chemistry. They catalyze the site-specific oxidation of a cysteine
      residue to the aldehyde-containing amino acid Calpha -formylglycine (FGly). This
      non-canonical residue can be generated within any desired target protein and can
      subsequently be used for bioorthogonal conjugation reactions. The prototypic
      formylglycine-generating enzyme (FGE) and the iron-sulfur protein AtsB display
      slight variations in their recognition sequences. We designed specific tags in
      peptides and proteins that were selectively converted by the different enzymes.
      Combination of the different tag motifs within a single peptide or recombinant
      protein enabled the independent and consecutive introduction of two formylglycine
      residues and the generation of heterobifunctionalized protein conjugates.

PMID- 29579348
TI  - A novel p.Pro353His SERPINC1 mutation in the thrombin-binding region affecting
      stability of Antithrombin molecule in an extended Omani family.

PMID- 29579349
TI  - Profiling of small molecule metabolites and neurotransmitters in crustacean
      hemolymph and neuronal tissues using reversed-phase LC-MS/MS.
AB  - Crustaceans have been long used as model animals for neuromodulation studies
      because of their well-defined neural circuitry. The identification of small
      molecule metabolites and signaling molecules in circulating fluids and neuronal
      tissues presents unique challenges due to their diverse structures, biological
      functions, and wide range of concentrations. LC combined with high resolution
      MS/MS is one of the most powerful tools to uncover endogenous small molecules.
      Here we explored several sample preparation techniques (solid-phase extraction
      and denaturing) and MS data acquisition strategies (data-dependent acquisition
      and targeted MS2-based acquisition) that provided complementary coverage and
      improved overall identification rate in C18 LC-MS/MS experiment. By MS/MS
      spectral matching with mzCloud database and those generated from standard
      compounds, a total of 129 small molecule metabolites and neurotransmitters were
      identified from crustacean hemolymph and neuronal tissues. These confidently
      identified small molecules covered predominant biosynthetic pathways for major
      neurotransmitters, validating the effectiveness of the high-throughput RPLC-MS/MS
      approach in studying the metabolism of neurotransmitters.

PMID- 29579350
TI  - A simple, fast, and accurate thermodynamic-based approach for transfer and
      prediction of gas chromatography retention times between columns and instruments
      Part I: Estimation of reference column geometry and thermodynamic parameters.
AB  - The transfer of retention times based on thermodynamic models between columns can
      aid in separation optimization and compound identification in gas chromatography.
      Although earlier investigations have been reported, this problem remains
      unsuccessfully addressed. One barrier is poor predictive accuracy when moving
      from a reference column or system to a new target column or system. This is
      attributed to challenges associated with the accurate determination of the
      effective geometric parameters of the columns. To overcome this, we designed
      least squares-based models that account for geometric parameters of the columns
      and thermodynamic parameters of compounds as they partition between mobile and
      stationary phases. Quasi-Newton-based algorithms were then used to perform the
      numerical optimization. In this first of three parts, the model used to determine
      the geometric parameters of the reference column and the thermodynamic parameters
      of compounds subjected to separation is introduced. As will be shown, the overall
      approach significantly improves the predictive accuracy and transferability of
      thermodynamic data (and retention times) between columns of the same stationary
      phase chemistry. The data required for the determination of the thermodynamic
      parameters and retention time prediction are obtained from fast and simple
      experiments. The proposed model and optimization algorithms were tested and
      validated using simulated and experimental data.

PMID- 29579351
TI  - Three-dimensional microfluidic chip with twin-layer herringbone structure for
      high efficient tumor cell capture and release via antibody-conjugated magnetic
      microbeads.
AB  - Harvesting rare circulating tumor cells (CTCs) from human blood is distinctly
      substantial to monitor tumor stage and evaluate therapeutic efficacy. As a proof
      of-concept study, a microfluidic chip with twin-layer herringbone grooves was
      developed to isolate and recover tumor cells with high efficiency based on the
      immunoreaction between cells and antibody-conjugated microbeads (MBs) under local
      magnetic field. Functional MBs were initially localized onto the internal channel
      wall through the magnetic guidance. Then, infused tumor cells were deviated into
      the herringbone groove via passive microvortex and were further trapped through
      an irreversible interaction with MBs. Upon the removal of magnet, the captured
      cells and residual MBs were released from the channel and collected for further
      analysis in cell adhesion and proliferation in vitro. Capture efficiency of tumor
      cells reached up to ~90% and limit of detection was down to 50 cells per mL based
      on this approach. Furthermore, recovery rate of tumor cells was as high as ~94%,
      and potencies of cell attachment and proliferation was well maintained in
      retrieved cells. Hence, the present technique has a great potential for the
      isolation, quantitation and recovery of CTCs for cancer theranostic guidance and
      biomolecular analysis.

PMID- 29579352
TI  - Cytologic-histologic correlation: Where are we now, and where are we going?
AB  - The author was the chair of a College of American Pathologists working group at
      the Gynecologic Cytopathology Quality Consensus Conference outlining then current
      practices in cytology-histology correlation, and published this work in the
      Archives of Pathology and Laboratory Medicine. Cancer Cytopathol 2018;126:301-8.
      Published 2018. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 29579353
TI  - Northern Italy in the American South: Assessing interobserver reliability within
      the Milan System for Reporting Salivary Gland Cytopathology.
AB  - BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)
      has been proposed to standardize salivary gland fine-needle aspiration (FNA)
      diagnoses. This study assessed salivary gland FNA results and risk of malignancy
      (ROM) rates at the University of North Carolina as well as the interobserver
      reliability (IOR) of the atypia of undetermined significance (AUS) and salivary
      gland neoplasm of uncertain malignant potential (SUMP) categories. METHODS: The
      electronic medical record was searched for FNA cases from 2010 to 2017 with
      subsequent surgical resections. Histologic diagnosis was used for gold-standard
      comparison. The original cytologic results were then converted into MSRSGC
      categories (nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, suspicious,
      and malignant). For the assessment of IOR, 23 cases were selected with enrichment
      for cases diagnosed as AUS (n = 11) or SUMP (n = 9). Six boarded cytopathologists
      and 1 cytopathology fellow assessed representative slides and provided an MSRSGC
      diagnosis for each case. Fleiss' kappa coefficients were calculated to determine
      IOR. RESULTS: The ROM was 33% for both AUS and SUMP cases; however, the risk of
      neoplasia was 56% for AUS cases and 100% for SUMP cases. Fleiss' kappa for the
      AUS category was 0.217 (P < .05), and Fleiss' kappa for the SUMP category was
      0.024 (P = .74). CONCLUSIONS: In this study assessing the IOR of MSRSGC
      categories, fair agreement and slight agreement were found for the AUS and SUMP
      categories, respectively. Observers preferentially used the AUS or benign
      neoplasm category for SUMP cases, perhaps because of unfamiliarity with SUMP as a
      diagnostic option. The initial adoption of a new reporting system will require a
      quality assessment to ensure that the system is reliable and useful for
      clinicians. Cancer Cytopathol 2018;126:390-6. (c) 2018 American Cancer Society.

PMID- 29579354
TI  - Penetrating head injuries in children presenting to the emergency department in
      Australia and New Zealand: A PREDICT prospective study.
AB  - AIM: Penetrating head injuries (pHIs) are associated with high morbidity and
      mortality. Data on pHIs in children outside North America are limited. We
      describe the mechanism of injuries, neuroimaging findings, neurosurgery and
      mortality for pHIs in Australia and New Zealand. METHODS: This was a planned
      secondary analysis of a prospective observational study of children <18 years who
      presented with a head injury of any severity at any of 10 predominantly
      paediatric Australian/New Zealand emergency departments (EDs) between 2011 and
      2014. We reviewed all cases where clinicians had clinically suspected pHI as well
      as all cases of clinically important traumatic brain injuries (death,
      neurosurgery, intubation >24 h, admission >2 days and abnormal computed
      tomography). RESULTS: Of 20 137 evaluable patients with a head injury, 21 (0.1%)
      were identified to have sustained a pHI. All injuries were of non-intentional
      nature, and there were no gunshot wounds. The mechanisms of injuries varied from
      falls, animal attack, motor vehicle crashes and impact with objects. Mean Glasgow
      Coma Scale on ED arrival was 10; 10 (48%) had a history of loss of consciousness,
      and 7 (33%) children were intubated pre-hospital or in the ED. Fourteen (67%)
      children underwent neurosurgery, two (10%) craniofacial surgery, and five (24%)
      were treated conservatively; four (19%) patients died. CONCLUSIONS: Paediatric
      pHIs are very rare in EDs in Australia and New Zealand but are associated with
      high morbidity and mortality. The absence of firearm-related injuries compared to
      North America is striking and may reflect Australian and New Zealand firearm
      regulations.

PMID- 29579355
TI  - The Role of ANA Determinations in Classification Criteria for SLE.
AB  - At present, an international group under the auspices of the American College of
      Rheumatology (ACR) and the European League Against Rheumatism (EULAR) is
      developing new criteria for the classification of patients with systemic lupus
      erythematosus (SLE) designed to be more sensitive and specific than existing
      criteria [1]. As discussed at the 2017 meeting of the ACR, an important feature
      of these criteria, which are based on a scoring system for clinical and
      laboratory domains, is the prominence of a positive antinuclear antibody (ANA) at
      a titer 1:80 or greater by immunofluorescence (IFA) as an entry criterion. This
      article is protected by copyright. All rights reserved.

PMID- 29579356
TI  - The high burden of alcoholic cirrhosis in privately insured persons in the United
      States.
AB  - : Alcoholic cirrhosis (AC) is a major cause of liver-related morbidity and
      mortality in the United States. Rising rates of alcohol use disorders in the
      United States will likely result in more alcoholic liver disease. Our aim was to
      determine the prevalence, health care use, and costs of AC among privately
      insured persons in the United States. We collected data from persons aged 18-64
      with AC (identified by codes from the International Classification of Diseases,
      Ninth and Tenth Revisions) enrolled in the Truven MarketScan Commercial Claims
      and Encounters database (2009-2015). We determined yearly prevalence, weighted to
      the national employer-sponsored, privately insured population. Using competing
      risk analysis, we estimated event rates for portal hypertensive complications and
      estimated the association between AC and costs as well as admissions and
      readmissions. In 2015, 294,215 people had cirrhosis and 105,871 (36%) had AC.
      Mean age at AC diagnosis was 53.5 years, and 32% were women. Over the 7 years
      queried, estimated national cirrhosis prevalence rose from 0.19% to 0.27% (P <
      0.001) and for AC from 0.07% to 0.10% (P < 0.001). Compared to non-AC, AC
      enrollees were significantly more likely to have portal hypertensive
      complications at diagnosis and higher yearly cirrhosis and alcohol-related
      admissions (25 excess cirrhosis admissions and 6.3 excess alcohol-related
      admissions per 100 enrollees) as well as all-cause readmissions. Per-person costs
      in the first year after diagnosis nearly doubled for AC versus non-AC persons
      (US$ 44,835 versus 23,319). CONCLUSION: In a nationally representative cohort of
      privately insured persons, AC enrollees were disproportionately sicker at
      presentation, were admitted and readmitted more often, and incurred nearly double
      the per-person health care costs compared to those with non-AC. (Hepatology
      2018).

PMID- 29579357
TI  - Venous Thromboembolic Events in Idiopathic Inflammatory Myopathy: Occurrence and
      Relation to Disease Onset.
AB  - OBJECTIVE: To assess the incidence of venous thromboembolic events (VTEs) in
      patients with idiopathic inflammatory myopathies (IIMs), to compare the incidence
      of VTEs in IIM to the incidence in the general population, and to identify
      patient categories at high risk and investigate the development of risk in
      relation to a diagnosis of IIM. METHODS: Using nationwide registers, we
      identified a cohort of 440 individuals with newly diagnosed IIM and 4,459
      individuals from the general population. Patients with IIM were diagnosed between
      2005 and 2011. The start of follow-up was the date of IIM diagnosis and the
      corresponding date in the general population. VTE was defined as hospital care
      with an International Statistical Classification of Diseases and Related Health
      Problems, Tenth Revision code indicating VTE, with a filled prescription for
      anticoagulant medication. Incidence rates including 95% confidence intervals (95%
      CIs) were calculated, and Cox proportional hazards models were used to compare
      the risk of VTE in patients with IIM to the risk in the general population.
      RESULTS: The incidence of VTEs was higher in patients with IIM than in the
      general population and was highest in patients who previously had cancer, who
      were ages >71 years when diagnosed with IIM, or who had dermatomyositis. The
      overall hazard ratio (HR) of VTE comparing the IIM cohort to the general
      population was 7.81 (95% CI 4.74, 12.85). The HR was highest the first year after
      IIM diagnosis, with HR 26.6 (95% CI 10.4, 68.0). CONCLUSION: Patients with IIM
      are at increased risk of VTE compared to the general population, especially
      during the first year after the diagnosis. Preventive measures should be focused
      on patients who previously have had cancer, who are ages >71 years when
      diagnosed, or who have dermatomyositis.

PMID- 29579358
TI  - A 22-Year-Old Woman With Systemic Lupus Erythematosus Presents With Two Damaged
      Kidneys, One Seizure, No Platelets, and Many Possible Diagnoses.

PMID- 29579359
TI  - Hepatic Lipogenesis and Brain Fatty Acid Profile in Response to Different Dietary
      n6/n3 Ratios and DHA/EPA Supplementation in Streptozotocin Treated Rats.
AB  - SCOPE: We investigated the interaction between streptozotocin (STZ)-induced
      diabetes and dietary n6/n3 ratio, and its influence on lipogenesis. METHODS AND
      RESULTS: The animals were treated with STZ and fed with different dietary n6/n3
      ratios: 1, 7, and 60, or supplemented with DHA/EPA. Gene expression was assessed
      by RT-PCR and protein expression by western blotting and immunohistochemistry.
      Fatty acid profile was determined by GC-MS. Pancreas and liver histology were
      assessed by hematoxylin and eosin (H&E) staining. STZ-induced characteristic
      changes in all STZ treated groups, including: increased blood glucose, decreased
      body mass, increased lipid peroxidation and CD36 expression, decreased 16:1n7 and
      18:1n7, increases in 20:3n6, decreases in phospholipid (PL) content of 20:4n6, as
      well as decreases in the expression of SREBP1c, Delta-9-desaturase (Delta9D), and
      Delta-5-desaturase (Delta5D). Additionally, other changes occurred that were
      dependent on the n6/n3 ratio. Among the diabetic groups, the lower n6/n3 ratio
      caused higher lipid peroxidation and CD36 expression, a greater decrease in
      20:4n6 and decreased Delta6-desaturase (Delta6D) expression, while the higher
      n6/n3 ratio caused increased partitioning of 20:4n6 into hepatic neutral lipids
      (NL), a decrease in 20:5n3 content, and increased beta-oxidation. CONCLUSION:
      Presented data suggest that the n6/n3 ratio could significantly influence
      lipogenesis, lipid peroxidation, and beta-oxidation in STZ-induced diabetes,
      which could have clinical significance.

PMID- 29579360
TI  - Use of capillary electrophoresis for characterisation of vinyl-terminated Au
      nanoprisms and nanooctahedra.
AB  - It is described a simple, rapid and efficient methodology to characterise and
      separate gold nanoprisms and nanooctahedra by capillary electrophoresis. This
      technique is suitable to distinguish between morphologies and it can be used as a
      powerful separation tool after a customised synthesis of both structures. This
      synthesis was carried out by amending two parameters, temperature and pH, and a
      sharp decrease was found in nanotriangles when temperature was increased from 70
      up to 95 degrees C. However, when the synthesis was performed at a given
      temperature, an increase in pH did not promote an important change in isolation
      of any structure until pH = 9.5, critical in the final morphology of the
      nanoparticle. Gold nanoprisms and nanooctahedra were successfully separated by
      capillary electrophoresis according to differences in charge-to-mass ratio of the
      morphologies. Final particle morphology was confirmed by transmission electron
      microscopy analysis. Under optimal working conditions, a mixture containing both
      shapes of gold nanoparticles was initially injected and two major peaks were
      obtained for each structure. Capillary electrophoresis allowed to study pH and
      temperature influence on both morphologies. It was inferred that the ratio
      between triangles and octahedra decreased to a great extent when increasing both
      temperature and pH.

PMID- 29579361
TI  - Utility of the BRAF p.V600E immunoperoxidase stain in FNA direct smears and cell
      block preparations from patients with thyroid carcinoma.
AB  - BACKGROUND: The identification of BRAF mutations in thyroid cancer has prognostic
      and therapeutic implications. Although the gold standard for identifying BRAF
      mutations is molecular testing, the ability to perform BRAF p.V600E
      immunostaining on fine-needle aspiration (FNA) samples can facilitate the rapid
      triaging of patients to treatment options. METHODS: A total of 50 thyroid
      carcinoma FNA samples, including papillary (29 samples), poorly differentiated
      (10 samples), anaplastic (9 samples), and Hurthle cell (2 samples) carcinomas,
      with a known BRAF p.V600E mutation status were selected for the current study.
      Immunostaining was performed on smears and cell block sections using an anti-BRAF
      p.V600E antibody (clone VE1). The results were compared with the known mutation
      status obtained by molecular testing and/or immunostaining of surgical pathology
      material from the same patient. RESULTS: Of the total of 50 cases, 26 cases had
      smears available for the evaluation of BRAF p.V600E immunostaining; positive
      immunostaining was noted in 16 samples and negative immunostaining was noted in 4
      samples, whereas 6 cases were equivocal. Of the 34 cases for which cell blocks
      were available for evaluation, BRAF p.V600E immunostaining was positive in 17
      cases, negative in 16 cases, and equivocal in 1 case. The overall sensitivity and
      specificity of BRAF p.V600E immunostaining on the cell block preparation was
      94.4% and 100%, respectively, whereas for the smears it was 80% and 63.6%,
      respectively. CONCLUSIONS: BRAF p.V600E immunostaining can be performed reliably
      on thyroid FNA cell block preparations. However, false-positive results on direct
      smears limit their utility and therefore need to be interpreted with caution.
      Cancer Cytopathol 2018;126:406-13. (c) 2018 American Cancer Society.

PMID- 29579363
TI  - Gout Severity, Socioeconomic Status, and Work Absence: A Cross-Sectional Study in
      Primary Care.
AB  - OBJECTIVE: To examine the association between gout severity and socioeconomic
      status (SES) and gout severity and work absence. METHODS: Postal questionnaires
      were sent to adult patients who were registered with 20 general practices and who
      had consultations regarding gout or had been prescribed allopurinol or colchicine
      in the preceding 2 years. Gout severity was defined using the following proxy
      measures: number of attacks, history of oligoarticular/polyarticular attacks,
      disease duration, and allopurinol use. SES was defined using the English index of
      multiple deprivation (area level) and using self-reported educational attainment
      (individual level). Work absence was defined as taking time off from work in the
      past 6 months because of gout. Adjusted odds ratios (ORadj ; 95% confidence
      intervals [95% CIs]) were calculated using logistic regression models (adjusted
      for age, sex, body mass index, gout severity, and comorbidities). RESULTS: A
      total of 1,184 completed questionnaires were returned. The mean age of patients
      was 65.6 years, and 84% were male. Not having attended further education
      ("further education" is defined as attendance after the statutory minimum school
      leaving age of 16 years) was associated with having had >=2 gout attacks in the
      last year (ORadj 0.54 [95% CI 0.36-0.81]) and oligoarticular/polyarticular
      attacks (ORadj 0.72 [95% CI 0.50-1.05]). Lower area-level deprivation was
      associated with fewer attacks (>=2) (ORadj 0.71 [95% CI 0.51-0.98]). Work absence
      was associated with having had >=2 gout attacks in the last year (ORadj 2.91 [95%
      CI 1.22- 6.92]), oligoarticular/polyarticular attacks (ORadj 3.10 [95% CI 1.46
      6.61]), and shorter disease duration (>18 years) (ORadj 0.13 [95% CI 0.03-0.50]).
      CONCLUSION: Gout severity was associated with individual-level deprivation,
      countering the historic and negative perception of gout as a "rich man's
      disease." The association of gout severity with work absence reinforces the
      argument for earlier urate-lowering therapy to prevent attacks from becoming
      frequent and debilitating.

PMID- 29579362
TI  - Barriers to the recognition of medullary thyroid carcinoma on FNA: Implications
      relevant to the new American Thyroid Association guidelines.
AB  - BACKGROUND: The 2016 American Thyroid Association guidelines recommend multiple
      endocrine neoplasia testing and evaluation for pheochromocytoma before
      thyroidectomy after a thyroid fine-needle aspiration biopsy (FNA) is positive for
      medullary thyroid carcinoma (MTC). In the current study, the authors examined the
      reasons why FNA was unable to definitively diagnose MTC preoperatively, with
      attention to morphologic patterns that can be misleading. METHODS: Cases of MTC
      diagnosed on thyroid surgical resection for which there was a prior FNA and
      slides available for review were included (28 cases). Clinicopathologic data were
      collected. Slides were reviewed for numerous features blinded to the original FNA
      interpretation. Morphologic features were compared between concordant cases (20
      cases) ("positive for MTC" or "suspicious for MTC") and discordant cases (4
      cases) (any other interpretation). Three cases of microscopic MTC (measuring <1
      cm) were excluded from statistical analysis, as was 1 case of sampling error
      (benign thyroid tissue). RESULTS: Nine men and 19 women were diagnosed with MTC.
      Four patients ultimately were diagnosed with multiple endocrine neoplasia, and 1
      had bilateral pheochromocytomas. At the time of surgical excision, the mean tumor
      size was 2.3 cm (range, 0.1-7.5 cm). Review of morphologic features demonstrated
      that the discrepant cases were significantly more likely to have limiting factors
      (air-drying artifact/excess blood), a cohesive pattern, or to lack plasmacytoid
      morphology. None of the discordant cases had pseudoinclusions or amyloid (finding
      was not statistically significant). CONCLUSIONS: The majority (86%) of thyroid
      FNAs from patients with MTC are concordant (positive/suspicious for MTC).
      Patterns of failure include sampling error and limited typical morphologic
      features, particularly a lack of plasmacytoid morphology and cellular dyshesion.
      A high level of suspicion for MTC is critical to ensure patients receive
      appropriate preoperative testing. Cancer Cytopathol 2018;126:397-405. (c) 2018
      American Cancer Society.

PMID- 29579364
TI  - ANA as an Entry Criterion in SLE Classification.
AB  - Thoughtful and eloquent as always, Drs. Pisetsky and Lipsky in their letter (1)
      highlight a critical point in the current SLE classification criteria project
      jointly supported by EULAR and ACR: if ANA positivity is to be the entry
      criterion, the sensitivity of the assay to detect ANA and that of ANA positivity
      for SLE are both important. Indeed, this issue has been a matter constantly
      discussed by the classification criteria steering committee since the beginning
      of the project. Our tenet is not that various ANA assays are comparable, but that
      ANA positivity is optimally positioned as an entry criterion for the
      classification of SLE (2). This article is protected by copyright. All rights
      reserved.

PMID- 29579365
TI  - News for CYTO 2018.

PMID- 29579367
TI  - Special Issue Title Page.

PMID- 29579366
TI  - Welcome to Prague CYTO 2018.

PMID- 29579368
TI  - Quantitative bioimage analysis of cell characteristics.

PMID- 29579369
TI  - Genomic mechanisms of fatigue in survivors of colorectal cancer.
AB  - BACKGROUND: Many cancer survivors experience fatigue as a nagging symptom lasting
      years after treatment. To learn of the relevant biological pathways involved in
      fatigue among cancer survivors, the authors tested for an association between
      fatigue levels and leukocyte gene expression profiles and determined the specific
      mediating immune cell types. METHODS: A sample of 89 Hispanic/Latino adults aged
      60.5 years, 62% of whom were male, who were diagnosed with colorectal cancer and
      were 2.9 years since diagnosis provided blood for transcriptome profiling and
      completed a validated measure of fatigue (Multidimensional Fatigue Symptom
      Inventory-Short Form). The authors applied genome-wide transcriptional profiling
      of leukocyte RNA to identify gene expression activity associated with fatigue,
      tested for the activity of specific transcription factors involved in previously
      established markers of inflammation and immunologic activation, and identified
      the specific cell types mediating these transcriptional alterations. RESULTS: In
      analyses adjusting for demographic and behavioral health risk factors, results
      linked fatigue with increased activation of B lymphocytes and CD8-positive T
      cells, as well as several transcription factors involved in immune activation
      (nuclear factor kappaB [NF-kappaB], signal transducer and activator of
      transcription [STAT], and cAMP responsive element-binding protein [CREB]).
      Results also replicated several specific genomic effects previously observed in
      fatigued cancer survivors, including upregulated expression of alpha-synuclein
      (SNCA) and hemoglobin subunits (HBA and HBB). CONCLUSIONS: Cancer survivors'
      heightened fatigue levels may be partially explained by activation of specific
      immune cell subsets, thereby providing a potential molecular biomarker for
      clinical interventions targeting the remediation of fatigue. Cancer 2018;124:2637
      44. (c) 2018 American Cancer Society.

PMID- 29579370
TI  - Encoding of Self-Referential Pain Catastrophizing in the Posterior Cingulate
      Cortex in Fibromyalgia.
AB  - OBJECTIVE: Pain catastrophizing is a common feature of chronic pain, including
      fibromyalgia (FM), and is strongly associated with amplified pain severity and
      disability. While previous neuroimaging studies have focused on evoked pain
      response modulation by catastrophizing, the brain mechanisms supporting pain
      catastrophizing itself are unknown. We designed a functional magnetic resonance
      imaging (fMRI)-based pain catastrophizing task whereby patients with chronic pain
      engaged in catastrophizing-related cognitions. We undertook this study to test
      our hypothesis that catastrophizing about clinical pain would be associated with
      amplified activation in nodes of the default mode network (DMN), which encode
      self-referential cognition and show altered functioning in chronic pain. METHODS:
      During fMRI, 31 FM patients reflected on how catastrophizing (CAT) statements
      (drawn from the Pain Catastrophizing Scale) impact their typical FM pain
      experience. Response to CAT statements was compared to response to matched
      neutral (NEU) statements. RESULTS: During statement reflection, higher fMRI
      signal during CAT statements than during NEU statements was found in several DMN
      brain areas, including the ventral (posterior) and dorsal (anterior) posterior
      cingulate cortex (vPCC and dPCC, respectively). Patients' ratings of CAT
      statement applicability were correlated solely with activity in the vPCC, a main
      DMN hub supporting self-referential cognition (r = 0.38, P < 0.05). Clinical pain
      severity was correlated solely with activity in the dPCC, a PCC subregion
      associated with cognitive control and sensorimotor processing (r = 0.38, P <
      0.05). CONCLUSION: These findings provide evidence that the PCC encodes pain
      catastrophizing in FM and suggest distinct roles for different PCC subregions.
      Understanding the brain circuitry encoding pain catastrophizing in FM will prove
      to be important in identifying and evaluating the success of interventions
      targeting negative affect in chronic pain management.

PMID- 29579373
TI  - Calcinosis of the Mandible in Dermatomyositis.

PMID- 29579372
TI  - Remitting Seronegative Symmetric Synovitis With Pitting Edema Associated With
      Partial Melanoma Response Under Anti-CTLA-4 and Anti-Programmed Death 1
      Combination Treatment.

PMID- 29579374
TI  - 2017 CPDD Peer Reviewers.

PMID- 29579371
TI  - Review: Synovial Cell Metabolism and Chronic Inflammation in Rheumatoid
      Arthritis.
AB  - Metabolomic studies of body fluids show that immune-mediated inflammatory
      diseases such as rheumatoid arthritis (RA) are associated with metabolic
      disruption. This is likely to reflect the increased bioenergetic and biosynthetic
      demands of sustained inflammation and changes in nutrient and oxygen availability
      in damaged tissue. The synovial membrane lining layer is the principal site of
      inflammation in RA. Here, the resident cells are fibroblast-like synoviocytes
      (FLS) and synovial tissue macrophages, which are transformed toward
      overproduction of enzymes that degrade cartilage and bone and cytokines that
      promote immune cell infiltration. Recent studies have shown metabolic changes in
      both FLS and macrophages from RA patients, and these may be therapeutically
      targetable. However, because the origins and subset-specific functions of
      synoviocytes are poorly understood, and the signaling modules that control
      metabolic deviation in RA synovial cells are yet to be explored, significant
      additional research is needed to translate these findings to clinical
      application. Furthermore, in many inflamed tissues, different cell types can
      forge metabolic collaborations through solute carriers in their membranes to meet
      a high demand for energy or biomolecules. Such relationships are likely to exist
      in the synovium and have not been studied. Finally, it is not yet known whether
      metabolic change is a consequence of disease or whether primary changes to
      cellular metabolism might underlie or contribute to the pathogenesis of early
      stage disease. In this review article, we collate what is known about metabolism
      in synovial tissue cells and highlight future directions of research in this
      area.

PMID- 29579375
TI  - Gabapentin and Pregabalin for the Treatment of Anxiety Disorders.

PMID- 29579376
TI  - Two Mechanisms Determine Quantum Dot Blinking.
AB  - Many potential applications of quantum dots (QDs) can only be realized once the
      luminescence from single nanocrystals (NCs) is understood. These applications
      include the development of quantum logic devices, single-photon sources, long
      life LEDs, and single-molecule biolabels. At the single-nanocrystal level, random
      fluctuations in the QD photoluminescence occur, a phenomenon termed blinking.
      There are two competing models to explain this blinking: Auger recombination and
      surface trap induced recombination. Here we use lifetime scaling on core-shell
      chalcogenide NCs to demonstrate that both types of blinking occur in the same
      QDs. We prove that Auger-blinking can yield single-exponential on/off times in
      contrast to earlier work. The surface passivation strategy determines which
      blinking mechanism dominates. This study summarizes earlier studies on blinking
      mechanisms and provides some clues that stable single QDs can be engineered for
      optoelectronic applications.

PMID- 29579377
TI  - Quantitative Investigation of the Role of Intra-/Intercellular Dynamics in
      Bacterial Quorum Sensing.
AB  - Bacteria utilize diffusible signals to regulate population density-dependent
      coordinated gene expression in a process called quorum sensing (QS). While the
      intracellular regulatory mechanisms of QS are well-understood, the effect of
      spatiotemporal changes in the population configuration on the sensitivity and
      robustness of the QS response remains largely unexplored. Using a microfluidic
      device, we quantitatively characterized the emergent behavior of a population of
      swimming E. coli bacteria engineered with the lux QS system and a GFP reporter.
      We show that the QS activation time follows a power law with respect to bacterial
      population density, but this trend is disrupted significantly by microscale
      variations in population configuration and genetic circuit noise. We then
      developed a computational model that integrates population dynamics with genetic
      circuit dynamics to enable accurate (less than 7% error) quantitation of the
      bacterial QS activation time. Through modeling and experimental analyses, we show
      that changes in spatial configuration of swimming bacteria can drastically alter
      the QS activation time, by up to 22%. The integrative model developed herein also
      enables examination of the performance robustness of synthetic circuits with
      respect to growth rate, circuit sensitivity, and the population's initial size
      and spatial structure. Our framework facilitates quantitative tuning of microbial
      systems performance through rational engineering of synthetic ribosomal binding
      sites. We have demonstrated this through modulation of QS activation time over an
      order of magnitude. Altogether, we conclude that predictive engineering of QS
      based bacterial systems requires not only the precise temporal modulation of gene
      expression (intracellular dynamics) but also accounting for the spatiotemporal
      changes in population configuration (intercellular dynamics).

PMID- 29579378
TI  - Sensitive Rapid Fluorescence Polarization Immunoassay for Free Mycophenolic Acid
      Determination in Human Serum and Plasma.
AB  - In this Article, we describe a fluorescence polarization immunoassay (FPIA) using
      a new label-near-infrared fluorescent dye. The developed FPIA method was
      optimized for the rapid analysis of free mycophenolic acid (MPA) in plasma of
      transplanted patients. The approach is based on the fluorescence competitive
      assay between the target immunosuppressant and a novel emissive near-infrared
      fluorescent dye-tagged MPA and MPA-AO for the binding sites of the anti-MPA
      antibody. The fluorescent analogue of MPA exhibits emission at 654 nm upon
      excitation at 629 nm (lambdaexcmax) and shows a good photochemical stability and
      a significant emission quantum yield (0.16) in phosphate buffer media. Free
      mycophenolic acid was isolated from blood or plasma samples using ultrafiltration
      prior to analysis. The sample was incubated for 20 min with 5 MUg/mL of anti-MPA
      antibody and 1 nM of MPA-AO before the measurements. The developed FPIA displays
      a limit of detection of 0.8 ng/mL (10% binding inhibition) and a dynamic range of
      1.7-39 ng/mL (20%-80% binding inhibition) in a PBST buffer, fitting the
      therapeutic requirements. The immunoassay selectivity was evaluated by measuring
      the cross-reactivity to other immunosuppressive drugs administered in combination
      with MPA (cyclosporin A and tacrolimus), as well as for the metabolite MPA
      glucuronide. The assay has been successfully applied to the analysis of free MPA
      in the blood of a heart-transplanted patient after oral administration of both
      mycophenolate mofetil (MMF) and tacrolimus, and the results have been compared
      with those obtained by rapid-resolution liquid chromatography with diode array
      detection (RRLC-DAD).

PMID- 29579379
TI  - Multiple Reaction Monitoring Tandem Mass Spectrometry Approach for the
      Identification of Biological Fluids at Crime Scene Investigations.
AB  - Knowledge of the nature of biofluids at a crime scene is just as important as DNA
      test to link the nature of the biofluid, the criminal act, and the dynamics of
      the crime. Identification of methods currently used for each biological fluid
      (blood, semen, saliva, urine) suffer from several limitations including
      instability of assayed biomolecules, and low selectivity and specificity; as an
      example of the latter issue, it is not possible to discriminate between alpha
      amylase 1 (present in saliva) and alpha-amylase 2 (present in semen and vaginal
      secretion. In this context, the aim of the work has been to provide a predictive
      protein signature characteristic of each biofluid by the recognition of specific
      peptides unique for each protein in a single analysis. A panel of four protein
      biomarkers for blood, four for saliva, five for semen, and two for urine has been
      monitored has been monitored by using a single multiple reaction monitoring (MRM)
      based method targeting concomitantly 46 different peptides. Then, The optimized
      method allows four biological matrices to be identified when present on their own
      or in 50:50 mixture with another biofluid. Finally, a valid strategy combining
      both DNA analysis and liquid chromatographic-tandem mass spectrometric multiple
      reaction monitoring (LC-MS-MRM) identification of biofluids on the same sample
      has been demonstrated to be particularly effective in forensic investigation of
      real trace evidence collected at a crime scene.

PMID- 29579380
TI  - Fluorescent Chemosensors as Future Tools for Cancer Biology.
AB  - It is well established that aberrant cellular biochemical activity is strongly
      linked to the formation and progression of various cancers. Assays that could aid
      in cancer diagnostics, assessing anticancer drug resistance, and in the discovery
      of new anticancer drugs are highly warranted. In recent years, a large number of
      small molecule-based fluorescent chemosensors have been developed for monitoring
      the activity of enzymes and small biomolecular constituents. These probes have
      shown several advantages over traditional methods, such as the ability to
      directly and selectively measure activity of their targets within complex
      cellular environments. This review will summarize recently developed fluorescent
      chemosensors that have potential applications in the field of cancer biology.

PMID- 29579381
TI  - Remote Control of Mammalian Cells with Heat-Triggered Gene Switches and
      Photothermal Pulse Trains.
AB  - Engineered T cells are transforming broad fields in biomedicine, yet our ability
      to control cellular activity at specific anatomical sites remains limited. Here
      we engineer thermal gene switches to allow spatial and remote control of
      transcriptional activity using pulses of heat. These gene switches are
      constructed from the heat shock protein HSP70B' (HSPA6) promoter, show negligible
      basal transcriptional activity, and activate within an elevated temperature
      window of 40-45  degrees C. Using engineered Jurkat T cells implanted in vivo, we
      use plasmonic photothermal heating to trigger gene expression at specific sites
      to levels greater than 200-fold. We show that delivery of heat as thermal pulse
      trains significantly increase cellular thermal tolerance compared to continuous
      heating curves with identical area-under-the-curve (AUC), enabling long-term
      control of gene expression in Jurkat T cells. This approach expands the toolkit
      of remotely controlled genetic devices for basic and translational applications
      in synthetic immunology.

PMID- 29579382
TI  - Identification of Lasso Peptide Topologies Using Native Nanoelectrospray
      Ionization-Trapped Ion Mobility Spectrometry-Mass Spectrometry.
AB  - Lasso peptides are a fascinating class of bioactive ribosomal natural products
      characterized by a mechanically interlocked topology. In contrast to their
      branched-cyclic forms, lasso peptides have higher stability and have become a
      scaffold for drug development. However, the identification and separation of
      lasso peptides from their unthreaded topoisomers (branched-cyclic peptides) is
      analytically challenging since the higher stability is based solely on
      differences in their tertiary structures. In the present work, a fast and
      effective workflow is proposed for the separation and identification of lasso
      from branched cyclic peptides based on differences in their mobility space under
      native nanoelectrospray ionization-trapped ion mobility spectrometry-mass
      spectrometry (nESI-TIMS-MS). The high mobility resolving power ( R) of TIMS
      resulted in the separation of lasso and branched-cyclic topoisomers ( R up to
      250, 150 needed on average). The advantages of alkali metalation reagents (e.g.,
      Na, K, and Cs salts) as a way to increase the analytical power of TIMS is
      demonstrated for topoisomers with similar mobilities as protonated species,
      efficiently turning the metal ion adduction into additional separation
      dimensions.

PMID- 29579384
TI  - High Mass Loading MnO2 with Hierarchical Nanostructures for Supercapacitors.
AB  - Metal oxides have attracted renewed interest as promising electrode materials for
      high energy density supercapacitors. However, the electrochemical performance of
      metal oxide materials deteriorates significantly with the increase of mass
      loading due to their moderate electronic and ionic conductivities. This limits
      their practical energy. Herein, we perform a morphology and phase-controlled
      electrodeposition of MnO2 with ultrahigh mass loading of 10 mg cm-2 on a carbon
      cloth substrate to achieve high overall capacitance without sacrificing the
      electrochemical performance. Under optimum conditions, a hierarchical
      nanostructured architecture was constructed by interconnection of primary two
      dimensional epsilon-MnO2 nanosheets and secondary one-dimensional alpha-MnO2
      nanorod arrays. The specific hetero-nanostructures ensure facile ionic and
      electric transport in the entire electrode and maintain the structure stability
      during cycling. The hierarchically structured MnO2 electrode with high mass
      loading yields an outstanding areal capacitance of 3.04 F cm-2 (or a specific
      capacitance of 304 F g-1) at 3 mA cm-2 and an excellent rate capability
      comparable to those of low mass loading MnO2 electrodes. Finally, the aqueous and
      all-solid asymmetric supercapacitors (ASCs) assembled with our MnO2 cathode
      exhibit extremely high volumetric energy densities (8.3 mWh cm-3 at the power
      density of 0.28 W cm-3 for aqueous ASC and 8.0 mWh cm-3 at 0.65 W cm-3 for all
      solid ASC), superior to most state-of-the-art supercapacitors.

PMID- 29579385
TI  - Silver-Catalyzed Radical Arylphosphorylation of Unactivated Alkenes: Synthesis of
      3-Phosphonoalkyl Indolines.
AB  - A silver-catalyzed phosphorylation/cyclization cascade of N-allyl anilines was
      developed, allowing direct access to 3-phosphonoalkyl indolines, which were
      previously obtainable only via tedious procedures under harsh/toxic conditions.
      The unactivated double bond serves as the radical acceptor, whereas H
      phosphonates or -phosphine oxides act as the radical precursor. This protocol
      features simple operation, broad substrate scope, and great exo selectivity, and
      a gram-scale synthesis could be readily carried out.

PMID- 29579383
TI  - Engineered Charge Redistribution of Gp2 Proteins through Guided Diversity for
      Improved PET Imaging of Epidermal Growth Factor Receptor.
AB  - The Gp2 domain is a protein scaffold for synthetic ligand engineering. However,
      the native protein function results in a heterogeneous distribution of charge on
      the conserved surface, which may hinder further development and utility. We aim
      to modulate charge, without diminishing function, which is challenging in small
      proteins where each mutation is a significant fraction of protein structure. We
      constructed rationally guided combinatorial libraries with charge-neutralizing or
      charge-flipping mutations and sorted them, via yeast display and flow cytometry,
      for stability and target binding. Deep sequencing of functional variants revealed
      effective mutations both in clone-dependent contexts and broadly across binders
      to epidermal growth factor receptor (EGFR), insulin receptor, and immunoglobulin
      G. Functional mutants averaged 4.3 charge neutralizing mutations per domain while
      maintaining net negative charge. We evolved an EGFR-targeted Gp2 mutant that
      reduced charge density by 33%, maintained net charge, and improved charge
      distribution homogeneity while elevating thermal stability ( Tm = 87 +/- 1 
      degrees C), improving binding specificity, and maintaining affinity ( Kd = 8.8 +/
      0.6 nM). This molecule was conjugated with 1,4,7-triazacyclononane,1-glutaric
      acid-4,7-acetic acid for 64Cu chelation and evaluated for physiological
      distribution in mice with xenografted A431 (EGFRhigh) and MDA-MB-435 (EGFRlow)
      tumors. Excised tissue gamma counting and positron emission tomography/computed
      tomography imaging revealed good EGFRhigh tumor signal (4.7 +/- 0.5%ID/g) at 2 h
      post-injection and molecular specificity evidenced by low uptake in EGFRlow
      tumors (0.6 +/- 0.1%ID/g, significantly lower than for non-charge-modified Gp2, p
      = 0.01). These results provide charge mutations for an improved Gp2 framework,
      validate an effective approach to charge engineering, and advance performance of
      physiological EGFR targeting for molecular imaging.

PMID- 29579386
TI  - Ab Initio Potential Energy Surfaces and Quantum Dynamics for Polyatomic
      Bimolecular Reactions.
AB  - There has been great progress in the development of potential energy surfaces
      (PESs) and quantum dynamics calculations in the gas phase. The establishment of a
      fitting procedure for highly accurate PESs and new developments in quantum
      reactive scattering on reliable PESs allow accurate characterization of reaction
      dynamics beyond triatomic systems. This review will give the recent development
      in our group in constructing ab initio PESs based on neural networks and the time
      dependent wave packet calculations for bimolecular reactions beyond three atoms.
      Bimolecular reactions of current interest to the community, namely, OH + H2, H +
      H2O, OH + CO, H + CH4, and Cl + CH4, are focused on. Quantum mechanical
      characterization of these reactions uncovers interesting dynamical phenomena with
      an unprecedented level of sophistication and has greatly advanced our
      understanding of polyatomic reaction dynamics.

PMID- 29579387
TI  - Generalized Density-Functional Tight-Binding Repulsive Potentials from
      Unsupervised Machine Learning.
AB  - We combine the approximate density-functional tight-binding (DFTB) method with
      unsupervised machine learning. This allows us to improve transferability and
      accuracy, make use of large quantum chemical data sets for the parametrization,
      and efficiently automatize the parametrization process of DFTB. For this purpose,
      generalized pair-potentials are introduced, where the chemical environment is
      included during the learning process, leading to more specific effective two-body
      potentials. We train on energies and forces of equilibrium and nonequilibrium
      structures of 2100 molecules, and test on ~130 000 organic molecules containing
      O, N, C, H, and F atoms. Atomization energies of the reference method can be
      reproduced within an error of ~2.6 kcal/mol, indicating drastic improvement over
      standard DFTB.

PMID- 29579388
TI  - Ordered Surface Structuring of Spherical Colloids with Binary Nanoparticle
      Superlattices.
AB  - Surface-patterning colloidal matter in the sub-10 nm regime generates exceptional
      functionality in biology and photonic and electronic materials. Techniques of
      artificially generating functional patterns in the small nanoscale advanced in a
      fascinating manner in the last several years. However, they remain often
      restricted to planar and noncolloidal substrates. Patterning colloidal matter in
      solution via bottom-up assembly of smaller subunits on larger core particles is
      highly challenging because it is necessary to force the subunits onto randomly
      moving objects. Consequently, the non-equilibrium conditions present during
      nanoparticle self-assembly are difficult to control to eventually achieve the
      desired material structures. Here, we describe the formation of surface patterns
      with intrinsic periodic repeats of 8.9 +/- 0.9 nm and less on hard, amorphous
      colloidal core particles by assembling binary nanoparticle superlattices on the
      curved particle surface. The colloidal environment is preserved during the entire
      bottom-up crystallization of variable building blocks (here, monodispersed 5 nm
      Au and 2.4 nm Pd nanoparticles (NPs) and 230 nm SiO2 core particles) into AB13
      like, binary, and isotropic superlattice domains on the amorphous cores. The
      three-dimensional, bottom-up assembly technique is a new tool for patterning
      colloidal matter in the sub-10 nm surface regime for gaining access to
      multicomponent metamaterials for bionanoscience, photonics, and electronics.

PMID- 29579389
TI  - Salt- and pH-Triggered Helix-Coil Transition of Ionic Polypeptides under
      Physiology Conditions.
AB  - Controlling the helix-coil transition of polypeptides under physiological
      conditions is an attractive way toward smart functional materials. Here, we
      report the synthesis of a series of tertiary amine-functionalized ethylene glycol
      (EG x)-linked polypeptide electrolytes with their secondary structures tunable
      under physiological conditions. The resultant polymers, denoted as P(EG xDMA-Glu)
      ( x = 1, 2, and 3), show excellent aqueous solubility (>20 mg/mL) regardless of
      their charge states. Unlike poly-l-lysine that can form a helix only at pH above
      10, P(EG xDMA-Glu) undergo a pH-dependent helix-coil switch with their transition
      points within the physiological range (pH ~5.3-6.5). Meanwhile, P(EG xDMA-Glu)
      exhibit an unusual salt-induced helical conformation presumably owing to the
      unique properties of EG x linkers. Together, the current work highlights the
      importance of fine-tuning the linker chemistry in achieving conformation
      switchable polypeptides and represents a facile approach toward stimuli
      responsive biopolymers for advanced biological applications.

PMID- 29579390
TI  - Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the
      Treatment of Atopic Dermatitis.
AB  - The histamine H4 receptor (H4R), a member of the G-protein coupled receptor
      family, has been considered as a potential therapeutic target for treating atopic
      dermatitis (AD). A large number of H4R antagonists have been disclosed, but no
      efficient agents controlling both pruritus and inflammation in AD have been
      developed yet. Here, we have discovered a novel class of orally available H4R
      antagonists showing strong anti-itching and anti-inflammation activity as well as
      excellent selectivity against off-targets. A pharmacophore-based virtual
      screening system constructed in-house successfully identified initial hit
      compound 9, and the subsequent homology model-guided optimization efficiently led
      us to discover pyrido[2,3- e]tetrazolo[1,5- a]pyrazine analogue 48 as a novel
      chemotype of a potent and highly selective H4R antagonist. Importantly, orally
      administered compound 48 exhibits remarkable efficacy on antipruritus and anti
      inflammation with a favorable pharmacokinetic (PK) profile in several mouse
      models of AD. Thus, these data strongly suggest that our compound 48 is a
      promising clinical candidate for treatment of AD.

PMID- 29579391
TI  - Modification of Bacterial Cellulose with Quaternary Ammonium Compounds Based on
      Fatty Acids and Amino Acids and the Effect on Antimicrobial Activity.
AB  - In the present work, bacterial cellulose (BC) membranes have been modified with
      bioactive compounds based on long chain dimer of C18 linoleic acid, referred to
      as the dilinoleic acid (DLA) and tyrosine (Tyr), a natural amino acid capable of
      forming noncovalent cation-pi interactions with positively charged ethylene
      diamine (EDA). This new compound, [EDA][DLA-Tyr], has been synthesized by simple
      coupling reaction, and its chemical structure was characterized by 1H NMR and
      Fourier transform infrared spectroscopy. The antimicrobial activity of a new
      compound against S. aureus and S. epidermidis, two cocci associated with skin and
      wound infections, was assessed. The [EDA][DLA-Tyr] impregnated BC exhibited
      strong and long-term antimicrobial activity against both staphylococcal species.
      The results showed a 57-66% and 56-60% reduction in S. aureus and S. epidermidis
      viability, respectively, depending on [EDA][DLA-Tyr] concentration used.
      Importantly, [EDA][DLA-Tyr] molecules were released gradually from the BC
      pellicle, while a reference antibiotic, erythromycine (ER), did not show any
      antibacterial activity against S. aureus and S. epidermidis after 48 h of soaking
      in deionized water. Thus, a combination of [EDA][DLA-Tyr] and BC could be a
      promising new class of wound dressing displaying both biocompatibility and
      antimicrobial activity.

PMID- 29579392
TI  - Template-Assisted Scalable Nanowire Networks.
AB  - Topological qubits based on Majorana Fermions have the potential to revolutionize
      the emerging field of quantum computing by making information processing
      significantly more robust to decoherence. Nanowires are a promising medium for
      hosting these kinds of qubits, though branched nanowires are needed to perform
      qubit manipulations. Here we report a gold-free templated growth of III-V
      nanowires by molecular beam epitaxy using an approach that enables patternable
      and highly regular branched nanowire arrays on a far greater scale than what has
      been reported thus far. Our approach relies on the lattice-mismatched growth of
      InAs on top of defect-free GaAs nanomembranes yielding laterally oriented, low
      defect InAs and InGaAs nanowires whose shapes are determined by surface and
      strain energy minimization. By controlling nanomembrane width and growth time, we
      demonstrate the formation of compositionally graded nanowires with cross-sections
      less than 50 nm. Scaling the nanowires below 20 nm leads to the formation of
      homogeneous InGaAs nanowires, which exhibit phase-coherent, quasi-1D quantum
      transport as shown by magnetoconductance measurements. These results are an
      important advance toward scalable topological quantum computing.

PMID- 29579393
TI  - Hybridization of Nitrogen Determines Hydrogen-Bond Acceptor Strength: Gas-Phase
      Comparison of Redshifts and Equilibrium Constants.
AB  - Gas-phase Fourier transform infrared spectroscopy and quantum chemical
      calculations are combined to illustrate the effect of hybridization on the
      hydrogen-bond acceptor strength of nitrogen by a comparison of nine bimolecular
      complexes. We present gas-phase results for the complexes of methanol, ethanol,
      and 2,2,2-trifluoroethanol with acetonitrile (sp-hybridized N) and find that the
      structure of these complexes is nearly linear and dominated by the OH...N
      hydrogen bond with no experimental indication of an OH-pi bonded structure. We
      compare experimental redshifts and equilibrium constants, obtained by combining
      experiments and theory, for these complexes to the corresponding complexes with
      pyridine (sp2-hybridized N) and trimethylamine (sp3-hybridized N). The comparison
      clearly illustrates that increasing the s-character of the nitrogen lone pair
      decreases the hydrogen-bond acceptor strength (sp3 > sp2 > sp). The observed
      trend correlates with the basicity of the acceptors and can be explained by the
      partial charge on the accepting nitrogen atom and the degree of localization of
      the nitrogen lone pair.

PMID- 29579394
TI  - Wire Placement into the Dural Venous Sinuses during Central Venous Catheter
      Placement.

PMID- 29579395
TI  - Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual
      Differences.
AB  - Genomewide association studies (GWASs) across psychiatric phenotypes have shown
      that common genetic variants generally confer risk with small effect sizes (odds
      ratio < 1.1) that additively contribute to polygenic risk. Summary statistics
      derived from large discovery GWASs can be used to generate polygenic risk scores
      (PRS) in independent, target data sets to examine correlates of polygenic
      disorder liability (e.g., does genetic liability to schizophrenia predict
      cognition?). The intuitive appeal and generalizability of PRS have led to their
      widespread use and new insights into mechanisms of polygenic liability. However,
      when currently applied across traits they account for small amounts of variance
      (<3%), are relatively uninformative for clinical treatment, and, in isolation,
      provide no insight into molecular mechanisms. Larger GWASs are needed to increase
      the precision of PRS, and novel approaches integrating various data sources
      (e.g., multitrait analysis of GWASs) may improve the utility of current PRS.

PMID- 29579396
TI  - Role of Spdef in the Regulation of Muc5b Expression in the Airways of Naive and
      Mucoobstructed Mice.
AB  - Understanding how expression of airway secretory mucins MUC5B and MUC5AC is
      regulated in health and disease is important to elucidating the pathogenesis of
      mucoobstructive respiratory diseases. The transcription factor SPDEF (sterile
      alpha-motif pointed domain epithelial specific transcription factor) is a key
      regulator of MUC5AC, but its role in regulating MUC5B in health and in
      mucoobstructive lung diseases is unknown. Characterization of Spdef-deficient
      mice upper and lower airways demonstrated region-specific, Spdef-dependent
      regulation of basal Muc5b expression. Neonatal Spdef-deficient mice exhibited
      reductions in BAL Muc5ac and Muc5b. Adult Spdef-deficient mice partially
      phenocopied Muc5b-deficient mice as they exhibited reduced Muc5b in
      nasopharyngeal and airway epithelia but not in olfactory Bowman glands, 75%
      incidence of nasopharyngeal hair/mucus plugs, and mild bacterial otitis media,
      without defective mucociliary clearance in the nasopharynx. In contrast, tracheal
      mucociliary clearance was reduced in Spdef-deficient mice in the absence of lung
      disease. To evaluate the role of Spdef in the development and persistence of
      Muc5b-predominant mucoobstructive lung disease, Spdef-deficient mice were crossed
      with Scnn1b-transgenic (Scnn1b-Tg) mice, which exhibit airway surface dehydration
      induced airway mucus obstruction and inflammation. Spdef-deficient Scnn1b-Tg mice
      exhibited reduced Muc5ac, but not Muc5b, expression and BAL content. Airway mucus
      obstruction was not decreased in Spdef-deficient Scnn1b-Tg mice, consistent with
      Muc5b-dominant Scnn1b disease, but increased airway neutrophilia was observed
      compared with Spdef-sufficient Scnn1b-Tg mice. Collectively, these results
      indicate that Spdef regulates baseline Muc5b expression in respiratory epithelia
      but does not contribute to Muc5b regulation in a mouse model of Muc5b-predominant
      mucus obstruction caused by airway dehydration.

PMID- 29579397
TI  - Dicer1 Deficiency in the Idiopathic Pulmonary Fibrosis Fibroblastic Focus
      Promotes Fibrosis by Suppressing MicroRNA Biogenesis.
AB  - RATIONALE: The lung extracellular matrix (ECM) in idiopathic pulmonary fibrosis
      (IPF) mediates progression of fibrosis by decreasing fibroblast expression of miR
      29 (microRNA-29), a master negative regulator of ECM production. The molecular
      mechanism is undefined. IPF-ECM is stiffer than normal. Stiffness drives
      fibroblast ECM production in a YAP (yes-associated protein)-dependent manner, and
      YAP is a known regulator of miR-29. Therefore, we tested the hypothesis that
      negative regulation of miR-29 by IPF-ECM was mediated by mechanotransduction of
      stiffness. OBJECTIVES: To determine how IPF-ECM negatively regulates miR-29.
      METHODS: We decellularized lung ECM using detergents and prepared polyacrylamide
      hydrogels of defined stiffness by varying acrylamide concentrations. Mechanistic
      studies were guided by immunohistochemistry of IPF lung and used cell culture,
      RNA-binding protein assays, and xenograft models. MEASUREMENTS AND MAIN RESULTS:
      Contrary to our hypothesis, we excluded fibroblast mechanotransduction of ECM
      stiffness as the primary mechanism deregulating miR-29. Instead, systematic
      examination of miR-29 biogenesis revealed a microRNA processing defect that
      impeded processing of miR-29 into its mature bioactive forms. Immunohistochemical
      analysis of the microRNA processing machinery in IPF lung specimens revealed
      decreased Dicer1 expression in the procollagen-rich myofibroblastic core of
      fibroblastic foci compared with the focus perimeter and adjacent alveolar walls.
      Mechanistically, IPF-ECM increased association of the Dicer1 transcript with RNA
      binding protein AUF1 (AU-binding factor 1), and Dicer1 knockdown conferred
      primary human lung fibroblasts with cell-autonomous fibrogenicity in zebrafish
      and mouse lung xenograft models. CONCLUSIONS: Our data identify suppression of
      fibroblast Dicer1 expression in the myofibroblast-rich IPF fibroblastic focus
      core as a central step in the mechanism by which the ECM sustains fibrosis
      progression in IPF.

PMID- 29579398
TI  - Response gene to complement 32 suppresses adipose tissue thermogenic genes
      through inhibiting beta3-adrenergic receptor/mTORC1 signaling.
AB  - Our previous studies have shown that response gene to complement (RGC)-32
      deficiency (Rgc32-/-) protects mice from diet-induced obesity and increases
      thermogenic gene expression in adipose tissues. However, the underlying
      mechanisms by which RGC-32 regulates thermogenic gene expression remain to be
      determined. In the present study, RGC-32 expression in white adipose tissue (WAT)
      was suppressed during cold exposure-induced WAT browning. Rgc32-/- significantly
      increased thermogenic gene expression in the differentiated stromal vascular
      fraction (SVF) of inguinal (i)WAT and interscapular brown adipose tissue (BAT).
      Rgc32-/- and cold exposure regulated a common set of genes in iWAT, as shown by
      RNA sequencing data. Pathway enrichment analyses showed that Rgc32-/- down
      regulated PI3K/Akt signaling-related genes. Akt phosphorylation was also
      consistently decreased in Rgc32-/- iWAT, which led to an increase in beta3
      adrenergic receptor (beta3-AR) expression and subsequent activation of mammalian
      target of rapamycin complex (mTORC)-1. beta3-AR antagonist SR 59230A and mTORC1
      inhibitor rapamycin blocked Rgc32-/--induced thermogenic gene expression in both
      iWAT and interscapular BAT. These results indicate that RGC-32 suppresses adipose
      tissue thermogenic gene expression through down-regulation of beta3-AR expression
      and mTORC1 activity via a PI3K/Akt-dependent mechanism.-Chen, S., Mei, X., Yin,
      A., Yin, H., Cui, X.-B., Chen, S.-Y. Response gene to complement 32 suppresses
      adipose tissue thermogenic genes through inhibiting beta3-adrenergic
      receptor/mTORC1 signaling.

PMID- 29579399
TI  - GSK3-activated STAT5 regulates expression of SFRPs to modulate adipogenesis.
AB  - Adipogenesis is a tightly regulated cellular process and is closely associated
      with obesity and its associated metabolic disorders, such as diabetes. Multiple
      transcription factors and signaling pathways are involved in the regulation of
      adipogenesis. Here, we report that glycogen synthase kinase (GSK3), which was
      reported to play an important role in many cellular processes, is essential to
      adipocyte differentiation at early and terminal differentiation phases.
      Mechanistically, GSK3 modulates adipogenesis through regulation of both canonical
      Wnt pathways, which involve Wnt/beta-catenin signaling, and noncanonical Wnt
      pathways, which include JNK and Ras-related C3 botulinum toxin substrate
      signaling. GSK3-regulated adipogenesis is also mediated by secreted frizzled
      related proteins (SFRPs), especially SFRP1, the canonical Wnt antagonist. The
      obesity-induced increase of Sfrp1 expression can be reversed by the GSK3
      inhibitor. GSK3-regulated expression of Sfrp is mediated by signal transducer and
      activator of transcription 5 (STAT5). We demonstrated that GSK3 activates STAT5
      through regulation of its phosphorylation to bind to the promoter of Sfrp genes
      and the peroxisome proliferator-activated receptor gamma gene to stimulate their
      expression, which could ultimately lead to a modulated adipogenic process. Our
      findings identify a GSK3/STAT5/SFRP/Wnt regulatory axis of adipogenesis and shed
      light on the molecular mechanism of adipogenesis by suggesting that different
      pathways and adipogenic regulators coordinately modulate adipocyte
      differentiation.-Wang L., Wang, Y., Meng, Y., Zhang, C., Di, L. GSK3-activated
      STAT5 regulates expression of SFRPs to modulate adipogenesis.

PMID- 29579401
TI  - Critical Comparison of Structured Contactors for Adsorption-Based Gas
      Separations.
AB  - Recent advances in adsorptive gas separations have focused on the development of
      porous materials with high operating capacity and selectivity, useful parameters
      that provide early guidance during the development of new materials. Although
      this material-focused work is necessary to advance the state of the art in
      adsorption science and engineering, a substantial problem remains: how to
      integrate these materials into a fixed bed to efficiently utilize the separation.
      Structured sorbent contactors can help manage kinetic and engineering factors
      associated with the separation, including pressure drop, sorption enthalpy
      effects, and external heat integration (for temperature swing adsorption, or
      TSA). In this review, we discuss monoliths and fiber sorbents as the two main
      classes of structured sorbent contactors; recent developments in their
      manufacture; advantages and disadvantages of each structure relative to each
      other and to pellet packed beds; recent developments in system modeling; and
      finally, critical needs in this area of research.

PMID- 29579400
TI  - Biomolecular Ultrasound and Sonogenetics.
AB  - Visualizing and modulating molecular and cellular processes occurring deep within
      living organisms is fundamental to our study of basic biology and disease.
      Currently, the most sophisticated tools available to dynamically monitor and
      control cellular events rely on light-responsive proteins, which are difficult to
      use outside of optically transparent model systems, cultured cells, or surgically
      accessed regions owing to strong scattering of light by biological tissue. In
      contrast, ultrasound is a widely used medical imaging and therapeutic modality
      that enables the observation and perturbation of internal anatomy and physiology
      but has historically had limited ability to monitor and control specific cellular
      processes. Recent advances are beginning to address this limitation through the
      development of biomolecular tools that allow ultrasound to connect directly to
      cellular functions such as gene expression. Driven by the discovery and
      engineering of new contrast agents, reporter genes, and bioswitches, the nascent
      field of biomolecular ultrasound carries a wave of exciting opportunities.

PMID- 29579403
TI  - Stable Radical Materials for Energy Applications.
AB  - Although less studied than their closed-shell counterparts, materials containing
      stable open-shell chemistries have played a key role in many energy storage and
      energy conversion devices. In particular, the oxidation-reduction (redox)
      properties of these stable radicals have made them a substantial contributor to
      the progress of organic batteries. Moreover, the use of radical-based materials
      in photovoltaic devices and thermoelectric systems has allowed for these emerging
      molecules to have impacts in the energy conversion realm. Additionally, the
      unique doublet states of radical-based materials provide access to otherwise
      inaccessible spin states in optoelectronic devices, offering many new
      opportunities for efficient usage of energy in light-emitting devices. Here, we
      review the current state of the art regarding the molecular design, synthesis,
      and application of stable radicals in these energy-related applications. Finally,
      we point to fundamental and applied arenas of future promise for these designer
      open-shell molecules, which have only just begun to be evaluated in full.

PMID- 29579404
TI  - Analytical Chemistry in the Regulatory Science of Medical Devices.
AB  - In the United States, regulatory science is the science of developing new tools,
      standards, and approaches to assess the safety, efficacy, quality, and
      performance of all Food and Drug Administration-regulated products. Good
      regulatory science facilitates consumer access to innovative medical devices that
      are safe and effective throughout the Total Product Life Cycle (TPLC). Because
      the need to measure things is fundamental to the regulatory science of medical
      devices, analytical chemistry plays an important role, contributing to medical
      device technology in two ways: It can be an integral part of an innovative
      medical device (e.g., diagnostic devices), and it can be used to support medical
      device development throughout the TPLC. In this review, we focus on analytical
      chemistry as a tool for the regulatory science of medical devices. We highlight
      recent progress in companion diagnostics, medical devices on chips for
      preclinical testing, mass spectrometry for postmarket monitoring, and
      detection/characterization of bacterial biofilm to prevent infections.

PMID- 29579405
TI  - Boron Doped Diamond: A Designer Electrode Material for the Twenty-First Century.
AB  - Boron doped diamond (BDD) is continuing to find numerous electrochemical
      applications across a diverse range of fields due to its unique properties, such
      as having a wide solvent window, low capacitance, and reduced resistance to
      fouling and mechanical robustness. In this review, we showcase the latest
      developments in the BDD electrochemical field. These are driven by a greater
      understanding of the relationship between material (surface) properties, required
      electrochemical performance, and improvements in synthetic growth/fabrication
      procedures, including material postprocessing. This has resulted in the
      production of BDD structures with the required function and geometry for the
      application of interest, making BDD a truly designer material. Current research
      areas range from in vivo bioelectrochemistry and neuronal/retinal stimulation to
      improved electroanalysis, advanced oxidation processes, supercapacitors, and the
      development of hybrid electrochemical-spectroscopic- and temperature-based
      technology aimed at enhancing electrochemical performance and understanding.

PMID- 29579406
TI  - A Life in Food: A Grain of Salt and Some Humble Pie.
AB  - From my senior school days, I had wanted to pursue a career in food. In quite
      what capacity I was not too sure. So my starting points were within the fields of
      animal nutrition before moving for the major part of my career to medical schools
      to study human nutrition and health. My career scientific achievements lie within
      the Kuhnian spectrum of normal science, but within that normality, I was always
      one to challenge conventional wisdom. An academic career is about more than just
      research. It is about teaching and not just the minutiae of nutrition, but about
      life and living, about challenges and failures. Reflecting on the experience of
      that career, my advice to early stage researchers is this: Be patient,
      determined, and resilient in the very early stages. Hold no fear of change and be
      courageous in challenging conventional wisdom. Always favor openness and
      collaboration and always seek to help others. Citation indices are important to
      your career, but these other avenues that I advise you to follow are what you
      will eventually be most proud of.

PMID- 29579402
TI  - Biodegradable Polymeric Nanoparticles for Therapeutic Cancer Treatments.
AB  - Polymeric nanoparticles have tremendous potential to improve the efficacy of
      therapeutic cancer treatments by facilitating targeted delivery to a desired
      site. The physical and chemical properties of polymers can be tuned to accomplish
      delivery across the multiple biological barriers required to reach diverse
      subsets of cells. The use of biodegradable polymers as nanocarriers is especially
      attractive, as these materials can be designed to break down in physiological
      conditions and engineered to exhibit triggered functionality when at a particular
      location or activated by an external source. We present how biodegradable
      polymers can be engineered as drug delivery systems to target the tumor
      microenvironment in multiple ways. These nanomedicines can target cancer cells
      directly, the blood vessels that supply the nutrients and oxygen that support
      tumor growth, and immune cells to promote anticancer immunotherapy.

PMID- 29579407
TI  - Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes:
      Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase
      (PI3K)/protein kinase B (Akt) pathway.
AB  - Ketamine is a widely used anesthetic in pediatric clinical practice. Previous
      studies have demonstrated that ketamine induces neurotoxicity and has a
      modulatory effect on the cells of the immune system. Here, we evaluated the
      potential protective effect and underlying mechanisms of natural phenolic
      compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat
      thymocytes were exposed to 100 uM ketamine alone or combined with increasing
      concentrations of curcumin (0.3, 1, and 3 MUM) for 24 hours. Cell viability was
      analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and
      propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen
      species (ROS) production and mitochondrial membrane potential [MMP] were measured
      by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for
      assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase
      (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin
      inhibitor. Ketamine induced toxicity in cells, increased the number of
      hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP.
      Co-incubation of higher concentrations of curcumin (1 and 3 MUM) with ketamine
      markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS
      production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a
      pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine
      effectively attenuated the ketamine-induced apoptosis in rat thymocytes.
      Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine
      significantly decreased the protective effect of curcumin on rat thymocytes. Our
      results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs
      through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt
      signaling pathway is involved in the anti-apoptotic effect of curcumin.

PMID- 29579408
TI  - Analysis of the association between CFH Y402H polymorphism and response to
      intravitreal ranibizumab in patients with neovascular age-related macular
      degeneration (nAMD).
AB  - Pharmacogenetic studies indicate that a variable response to anti-vascular
      endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD
      (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This
      study is the first to investigate the association between CFH Y402H polymorphism
      and the response to ranibizumab therapy in Malaysian patients with nAMD. We
      included 134 patients with nAMD, examined between September 2014 and February
      2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before
      ranibizumab therapy was started. Each patient received an intravitreal injection
      of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best
      corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded
      after 3 and 6 months following the first injection and compared with the baseline
      values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP
      and the amplified product was digested with MluCI restriction enzyme. Association
      between the Y402H genotypes and response to treatment was determined by a
      logistic regression analysis of responder (n = 49) and non-responder (n = 84)
      group. Significantly worse mean BCVA was observed for the CC genotype compared to
      the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018).
      Comparing the baseline and 6-month point measurements, improved mean BCVA was
      observed in responder group, while worse mean BCVA was recorded for non-responder
      group. However, our regression analysis, adjusted for confounding factors, showed
      no significant association between the Y402H genotypes and response to treatment
      in nAMD patients under the recessive model (p > 0.05). Overall, our results
      suggest that factors other than Y402H polymorphism may be involved in the
      progression of nAMD after treatment with anti-VEGF agents, in Malaysian
      population.

PMID- 29579409
TI  - The effect of 131I-induced hypothyroidism on the levels of nitric oxide (NO),
      interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), total nitric oxide
      synthase (NOS) activity, and expression of NOS isoforms in rats.
AB  - Accumulating evidence has shown that hypothyroidism affects the cardiovascular
      system, significantly increasing the incidence of cardiovascular diseases. In the
      present study we investigated the effect of radioactive iodine (I-131)-induced
      hypothyroidism on several parameters of vascular function, such as nitric oxide
      (NO), total nitric oxide synthase (NOS) activity and expression of NOS isoforms,
      as well as on interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) as
      indicators of inflammation, in rats. A dose of 150 uCi of 131-I was determined as
      optimal for establishing the model of hypothyroidism in rats. After
      administration of 131-I, at the end of month 1, 2, and 4 (n = 3 for each time
      point), NO, IL-6, and TNF-alpha in the serum and total NOS activity in the aorta
      were determined in 150 uCi group, compared to controls. The mRNA and protein
      expression of endothelial, neuronal, and inducible NOS (eNOS, nNOS, and iNOS) in
      the rat aorta was also estimated, using quantitative reverse transcription
      polymerase chain reaction and Western blot, respectively. The levels of IL-6 and
      TNF-alpha increased in 150 uCi group; the results were significant at the end of
      month 2 and 4 for IL-6, and at all time points for TNF-alpha. The levels of NO
      decreased significantly at the end of month 2 and 4 in 150 uCi group. The total
      NOS activity increased significantly in 150 uCi group, at all three time points.
      Significant changes in the mRNA and protein expression of all three NOS isoforms
      were observed in 150 uCi group compared to controls. NO, IL-6, TNF-alpha levels
      and NOS activity and expression are altered in hypothyroid state, and the
      underlying mechanism should be further investigated.

PMID- 29579410
TI  - Dose and administration protocol for FSH used for ovarian stimulation affect gene
      expression in sheep cumulus?oocyte complexes.
AB  - The present study evaluated the effect of four ovarian stimulation protocols on
      the follicular population and molecular status of cumulus-oocyte complexes
      (COCs). Twelve Santa Ines ewes (in a cross-over design) received 80 or 120mg FSH
      alone in a multiple-dose (MD80 and MD120) regimen or in combination with 300IU
      equine chorionic gonadotrophin (eCG) in a one-shot (OS80 and OS120) protocol. The
      follicular population, COC recovery rate, mean COCs per ewe and the rate of
      brilliant Cresyl blue-positive (BCB+) COCs were similar among treatments
      (P>0.05). The expression of markers of oocyte competence (ZAR1, zygote arrest 1;
      MATER, maternal antigen that embryo requires; GDF9, growth differentiation factor
      9; BMP15, bone morphogenetic protein 15; Bcl-2, B-cell lymphoma 2; BAX, Bcl-2
      associated X protein) and the steroidogenic pathway (ERalpha, oestrogen receptor
      alpha; LHr, LH receptor; FSHr, FSH receptor; STAR, steroidogenic acute regulatory
      protein) was affected by stimulation. Specifically, the expression of markers of
      the steroidogenic pathway was reduced with increasing FSH dose in the OS
      protocol. FSH at a dose of 80mg reduced the expression of FSHr and ERalpha in the
      OS versus MD protocol. Conversely, in MD protocol, only LHr was affected by
      increasing FSH dose. In conclusion, 80mg FSH in the MD or OS protocol was
      sufficient to promote the development of multiple follicles and obtain fully
      grown (BCB+) oocytes. The MD protocol may be more appropriate for the production
      of better-quality oocytes.

PMID- 29579411
TI  - Comparative expression of PEDF and VEGF in human epidermal keratinocytes and
      dermal fibroblasts: from normal skin to psoriasis.
AB  - Vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor
      (PEDF) have been shown to keep angiogenesis activation and inhibition in balance
      in normal and pathological conditions. In this study, we examined the expression
      of VEGF and PEDF in keratinocytes and fibroblasts from normal and psoriatic skin
      to evaluate their potential roles and interactions in the development of
      psoriasis. The expression of VEGF and PEDF was detected in normal and psoriatic
      skin ex vivo and in co-cultured keratinocytes and fibroblasts in vitro, and
      increased in keratinocytes and fibroblasts from psoriatic skin compared with
      those cells from normal skin. Our results suggest that PEDF act as a multipotent
      factor in the skin and the imbalance of PEDF and VEGF may be responsible for the
      transformation from normal skin to psoriasis.

PMID- 29579412
TI  - Urine biomarkers in the early stages of diseases: current status and perspective.
AB  - As a noninvasive and easily available biological fluid, the urine is becoming an
      important source for disease biomarker study. Change is essential for the
      usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate
      more changes, especially in the early stages of diseases. In this review, we
      summarize current status and discuss perspectives on the discovery of urine
      biomarkers in the early stages of diseases. We emphasize the advantages of urine
      biomarkers compared to plasma biomarkers for the diagnosis of diseases at early
      stages, propose a urine biomarker research roadmap, and highlight a novel
      membrane storage technique that enables large-scale urine sample collection and
      storage efficiently and economically. It is anticipated that urine biomarker
      studies will greatly promote early diagnosis, prevention, treatment, and
      prognosis of a variety of diseases, and provide strong support for translational
      and precision medicine.

PMID- 29579413
TI  - The unusual nutritional and toxin-related underproduction anemias: approaching
      the riddle beyond iron, cobalamin, and folate.
AB  - "Anemias beyond iron, vitamin B12, and folate deficiencies" covers a wide array
      of everything which lies beyond commonly seen anemias caused by deficiencies of
      three micronutrients. Although anemias due to deficiencies of iron, B12, and
      folate are common in daily practice and account for at least one-third of anemia
      etiologies in older adults, it is not uncommon to encounter other nutritional and
      toxin-induced underproduction anemias. The combination of thorough clinical
      examination, careful peripheral blood smear review, and judicious selection of
      supporting laboratory studies is typically sufficient to make an assertive
      diagnosis of those cases. Moreover, the recognition of overlapping features with
      primary hematologic disorders and the diagnostic limitations of conventional
      testing are important for clinicians to determine when to refer to a
      hematologist. Herein, we discuss clinical features and diagnostic approaches to
      unusual underproduction anemias due to deficiencies of vitamin B6 and copper, and
      toxic effects of alcohol and lead.

PMID- 29579415
TI  - A Timely Evaluation of the Psychometric Properties of the KDQOL-36.

PMID- 29579414
TI  - Triggers of inflammatory myopathy: insights into pathogenesis.
AB  - The inflammatory myopathies, which include dermatomyositis, polymyositis, and the
      immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune
      diseases that manifest with muscle, skin, or lung damage. Collectively, these
      autoimmune diseases result from loss of tolerance to a select group of self
      antigens, although the precise mechanism through which this occurs is not known.
      Infection, malignancy, and certain medications including statins and the immune
      checkpoint inhibitors used in cancer therapy have been identified as potential
      immunologic triggers of the inflammatory myopathies. Some of these triggers are
      classically associated with specific myositis-specific autoantibodies (MSAs). The
      strong association between certain triggers and MSAs provides insights into how
      an immunologic event can lead to loss of tolerance to specific self-antigens,
      resulting in autoimmune disease. In this review, we discuss the proposed triggers
      of the inflammatory myopathies and their associations with MSAs, and provide
      insights into how these triggers may result in the inflammatory myopathies.

PMID- 29579416
TI  - Lessons From International Differences in Vascular Access Practices and Outcomes.

PMID- 29579417
TI  - Rising Peritoneal Dialysis Tide May Still Leave Some Patients Behind.

PMID- 29579418
TI  - Erratum Regarding "US Renal Data System 2017 Annual Data Report: Epidemiology of
      Kidney Disease in the United States" (Am J Kidney Dis. 2018;71[3][suppl
      1]:Svii,S1-S676).

PMID- 29579419
TI  - Nephrocalcinosis: A Diagnostic Conundrum.

PMID- 29579420
TI  - AJKD Atlas of Renal Pathology: Pierson Syndrome.

PMID- 29579421
TI  - Inflammation plays a central role in respiratory diseases, including
      tuberculosis.

PMID- 29579422
TI  - Too little too late: Waiting for TB to come.
AB  - There is a new paradigm that preventing tuberculosis (TB) and addressing the
      reservoir of latent TB infection in combination with curing all TB cases is
      essential to accelerate the decline of TB rates and ending TB by 2050. However,
      complacency and incremental change eludes radical policy transformation needed to
      meet global targets. This essay explores current attitudes, policy disparities
      between high and lower burden settings, and what changes are needed to remove the
      obstacles to progress.

PMID- 29579423
TI  - Modalities to monitor the treatment response in tuberculosis.
AB  - Considering the global epidemic of drug resistance in Mycobacterium tuberculosis,
      early and accurate diagnosis as well as prompt initiation of antitubercular
      therapy (ATT) forms the mainstay of tuberculosis control programs. Patients on
      ATT may develop treatment failure due to diverse reasons including emergence of
      drug resistance in the host during the course of therapy. Monitoring the timely
      response to treatment in such cases has a significant role in rapid
      identification of drug resistant strains and institution of change of regimen to
      further decrease the morbidity and mortality associated with the disease.
      Furthermore, availability of faster surrogate end points to assess treatment
      efficacy, disease activity, cure, and relapse is one of the crucial requirements
      for undertaking innovative clinical trials related to TB. The article presents
      here the compilation of currently available methods for monitoring the treatment
      response in pulmonary as well as extrapulmonary TB.

PMID- 29579424
TI  - A selective and sensitive high performance liquid chromatography assay for the
      determination of cycloserine in human plasma.
AB  - BACKGROUND: Cycloserine (CYC) is a second line antitubercular drug that is used
      for the treatment of multidrug resistant tuberculosis (MDR-TB) along with other
      antitubercular agents and is often used in developing countries. Monitoring CYC
      levels in plasma could be useful in the clinical management of patients with MDR
      TB. A high performance liquid chromatography method for the determination of CYC
      in human plasma was developed. METHODS: The method involved extraction of the
      sample using solid phase extraction cartridges and analysis of the extracted
      sample using a reverse phase T3 column (150mm) and detection at 240nm with Photo
      Diode Array (PDA) detector. The chromatogram was run for 15min at a flow rate of
      0.4ml/min at 30 degrees C. RESULTS AND CONCLUSION: The assay was specific for CYC
      and linear from 5.0 to 50.0MUg/ml. The relative standard deviations of within-
      and between-day assays were less than 10%. Recovery of CYC ranged from 102% to
      109%. The interference of other second line anti-TB drugs in the assay of CYC was
      ruled out. The assay spans the concentration range of clinical interest. The
      specificity and sensitivity of this assay makes it highly suitable for
      pharmacokinetic studies.

PMID- 29579425
TI  - Knowledge of private practitioners of Bangalore city in diagnosis, treatment of
      pulmonary tuberculosis and compliance with case notification.
AB  - One hundred and twenty-nine qualified private practitioners (PPs) were assessed
      on their knowledge in diagnosis of pulmonary tuberculosis (PTB), treatment of a
      new drug sensitive PTB case and practices of case notification, using semi
      structured questionnaire. About 20% had adequate knowledge of diagnosis, 29% of
      treatment regimen, 54% the need for Direct Observation Treatment and 57% about
      role of sputum smear examination in monitoring treatment response. Of 85 (68%)
      PPs who had diagnosed any TB case during last two years, 54 (64%) had practised
      notification. These findings suggest the need for upgrading knowledge of PPs in
      TB diagnosis, treatment and notification.

PMID- 29579426
TI  - Prevalence of pulmonary tuberculosis among adults in selected slums of Delhi
      city.
AB  - BACKGROUND: A survey was carried out to estimate the point prevalence of
      bacteriologically positive pulmonary tuberculosis (PTB) among persons >=15 years
      of age residing in Jhuggi-Jhopri (JJ) colonies - urban slums in Delhi, India
      implementing Directly Observed Treatment strategy since 1998. METHODS: Among 12
      JJ colonies selected by simple random sampling, persons having persistent cough
      for >=2 weeks at the time of the survey or cough of any duration along with
      history of contact/currently on ant-TB treatment/known HIV positive were
      subjected to sputum examination - 2 specimens, by smear microscopy for Acid Fast
      Bacilli and culture for Mycobacterium tuberculosis. Persons with at least one
      specimen positive were labelled as bacteriologically confirmed PTB. Prevalence
      was estimated after imputing missing values to correct bias introduced by
      incompleteness of data and corrected for non-screening by X-ray by a
      multiplication factor derived from recently conducted surveys. RESULTS: Of 40,756
      persons registered, 40,529 (99.4%) were screened. Of them, 691 (2%) were eligible
      for sputum examination. Spot specimens were collected from 659 (99.2%) and early
      morning sputum specimens from 647 (98.1%). Using screening by interview alone,
      prevalence of bacteriologically positive PTB in persons >=15 years of age was
      estimated at 160.4 (123.7-197.1) per 100,000 populations and210.0 (CI: 162.5
      258.2) after correcting for non-screening by X-ray. CONCLUSION: Observed
      prevalence suggests further strengthening of TB control program in urban slums.

PMID- 29579427
TI  - Factors predicting treatment success in multi-drug resistant tuberculosis
      patients treated under programmatic conditions.
AB  - BACKGROUND: Treatment success in multi-drug resistant tuberculosis under
      programmatic conditions has been far from satisfactory. Knowledge of the factors
      predicting treatment outcome can guide us to take appropriate corrective measures
      for better results. However, there is a scarcity of data on these predictors in
      Indian patients. The present study was sought to evaluate association of
      different patient and disease specific factors with treatment outcome in MDR-TB
      patients. METHODS: It was a retrospective study that involved evaluation of data
      of MDR-TB patients who were started on Cat-IV treatment between January 2012 and
      December 2014. Medical records of 256 patients were scrutinized and necessary
      information on possible predicting factors like age, gender, body mass index, co
      morbidities, previous TB treatment, blood investigations, treatment adherence,
      culture conversion time, etc. was retrieved. These factors were analyzed for
      their possible association with treatment outcome. RESULTS: Of the 256 patients,
      132 (51.6%) achieved successful outcome after Cat-IV anti-TB regimen. On
      multivariate logistic regression analysis age (adjusted OR=0.95; 95% CI 0.91
      0.98; p=0.01), serum albumin level (adjusted OR=3.71; 95% CI: 1.22-11.3; p=0.02)
      and treatment adherence (adjusted OR=4.52; 95% CI: 1.2-16.6; p=0.02) were
      independently associated with treatment success. Co-morbidities like diabetes and
      alcoholism and previous anti-TB treatment didn't affect the treatment end result
      significantly. CONCLUSION: The treatment outcome in MDR-TB has not significantly
      improved since the inception of DOTS-Plus strategy. Interventions to improve
      nutrition and treatment adherence might help to improve the success rate in MDR
      TB treatment.

PMID- 29579428
TI  - Socio-demographic profile and outcome of TB patients registered at DTC Rewa of
      Central India.
AB  - BACKGROUND: Tuberculosis is a specific infectious disease caused by Mycobacterium
      tuberculosis. The disease is usually chronic with cardinal features such as
      persistent cough with or without expectoration, intermittent fever, and loss of
      appetite, weight loss, chest pain and hemoptysis. OBJECTIVE: (1) To assess the
      socio-demographic profile of the patients attending DOTS Center. (2) To assess
      outcome of treatment under DOTS Center. METHODOLOGY: This is a Prospective
      Longitudinal study conducted among the patients attending DOTS center of DTC
      located at S.G.M.H. campus Rewa Madhya Pradesh Central India, during the last
      quarter of 2014, Study Duration: One year and two months i.e. starting from 1st
      September 2014 to 31st October 2015; total study sample size consisted of 137
      patients who were newly registered during the last quarter of 2014 (from 1st
      October to 31st December 2014) at DOTS Center of DTC. After applying inclusion
      and exclusion criteria, a total of 133 newly registered patients were enrolled
      that can be considered as total sample size in the present study. RESULT: Study
      population comprises a total of 133 patients; out of which 84 (63.15%) were male
      and 49 (36.84%) were female. In both most common age group are 21-30 year were 41
      (30.82%) patients and least common was pediatric TB in age group <10 year were 10
      (7.51%) patients, lower socio-economic class (class-V) 53.38% followed by class
      IV or Lower middle class 29.32%, only 1.5% were from upper class. 96 (72.18%)
      patients were of category-I patient and 37 (27.81%) were category-II patient, 51
      (38.34%) patients were cured, 70 (52.63%) had their treatment completed, so
      overall treatment success rate was 90.97%; in that, 2 cases were (1.50%) failure,
      4 (3%) defaulters, 2 (1.50%) died during treatment and 4 (3%) were transferred
      out. CONCLUSION: Study concluded that most of the patients belonged to lower
      socioeconomic status and in productive age group so it will increase the economic
      burden over the family; therefore, after increasing the living standard the
      outcome of disease becomes favorable.

PMID- 29579429
TI  - Tuberculosis related stigma and its effect on the delay for sputum examination
      under the Revised National Tuberculosis Control Program in India.
AB  - BACKGROUND: One major barrier to achieve goal of tuberculosis (TB) control
      program globally, is the stigma attached to the disease. Perceived stigma can
      delay sputum test in time. Delay will lead to spread of infection in the
      community. There is no scientific information available in India exactly looking
      into the association between delay in sputum examination and stigma. AIM: We
      conducted a study in rural West Bengal among persons with cough for 2 weeks or
      more to assess their level of stigma, its influence on delay for sputum test and
      identify factors those shape the level of stigma. METHODS: A community based
      cross sectional survey was conducted from February to June 2015 in West Bengal,
      India. We interviewed 135 persons of 15-60 years. Data were collected using a
      pretested structured questionnaire. Chi-square and logistic regression analysis
      were done using SPSS 23.0 statistical software. RESULTS: Among the 'lower stigma'
      group (score 4-24), 'delay' (14-25 days) is found among 46.2% respondents and
      'much delay' (26-120 days) among 53.8%. Among the 'higher stigma' (score 25-36)
      group, 'delay' is found among 20.5% respondents and 'much delay' among 79.5%.
      Persons with lower stigma are 0.17 times likely to delay than persons with higher
      stigma [adjusted odds ratio (AOR): 0.17 (0.044-0.668), p=0.011)]. Important
      influencers of stigma are caste [AOR: 5.90 (1.66-20.90), p=0.006], number of
      family members [AOR: 3.46 (1.08-11.06), p=0.009] and residence in urban or rural
      [AOR: 3.97 (1.03-15.27), p=0.045]. CONCLUSION: Revised National Tuberculosis
      Control Program in India should de-stigmatize the community giving priorities to
      lower castes, big families and rural areas.

PMID- 29579430
TI  - Expression profile of CXCL12 chemokine during M. tuberculosis infection with
      different therapeutic interventions in guinea pig.
AB  - Mycobacterium indicus pranii (MIP) already established as an immune-modulator in
      mycobacterial infections generates immune response by acting on CXC chemokines.
      In the present study, the immunomodulatory effect of MIP in conjunction with
      chemotherapy against M.tb infection was evaluated by colony forming units (CFUs)
      following aerosol infection to guinea pig and by measuring CXCL12 chemokine
      expression using q-PCR and in situ RT-PCR. Different experimental groups
      included, infection (Rv), immunoprophylaxis (RvMw), chemotherapy (RvCh) and
      combination of immunoprophylaxis+chemotherapy (RvChMw) group and normal healthy
      (NH) group. In the combination of immunoprophylaxis+chemotherapy (RvChMw) group,
      the CFU counts reduced significantly (p<0.001) at 4th week of infection as
      compared to other treated groups (RvMw and RvCh group). The expression of CXCL12
      was recorded in all the treated groups of animals. The study demonstrated
      suppressed expression of CXCL 12 in both immunoprophylaxis as well as
      chemotherapy groups (6th and 8th week) that become elevated in immunoprophylaxis
      plus chemotherapy group (10th week), at which time point no CFUs were detected in
      RvCh and RvChMw group. The findings indicate that the expression of CXCL12 is
      associated with good response to anti - tubercular treatment. Thus, prior
      immunization with MIP appears to show good immunomodulatory effect to release
      CXCL12 chemokine during infection and also correlates with enhanced effect to
      chemotherapy.

PMID- 29579431
TI  - Quality of life of diabetic patients with smear positive PTB in southeastern
      Iran: A cross-sectional study in a poor region of Iran.
AB  - BACKGROUND: The quality of life is an important indicator of quality of care in
      chronic diseases such as diabetes and TB. The present research is conducted with
      an aim to assess the Quality of Life of Diabetic Patients with Smear Positive
      PTB. METHODS: This cross-sectional study was conducted on 62 diabetic patients
      with smear positive PTB from January to May 2016 in a diabetes clinic in Zahedan
      city (southeast of Iran). A simple random sampling method was used in this study.
      Instrument for data collection was quality of life (SF-36) questioner. RESULTS:
      Total quality of life score was 48 that showed an average level of quality of
      life. Sixty-five patients with diabetes and affected by smear positive pulmonary
      tuberculosis (PTB) with the average age of 51.30+/-10.84 years participated in
      this research. Four patients (0.06%) suffered from type 1 diabetes and 58 (94%)
      from type 2 diabetes, and all of them were smear positive PTB patients. Study of
      their quality of life revealed that, in general, the average scores for quality
      of life in the two main subgroups of physical health and mental health were lower
      than the average and, among the eight studied dimensions, the highest scores were
      those for physical activity (60+/-14.23) and the lowest (31.42+/-12.14) for
      general health in the subgroup of physical health. CONCLUSION: Results indicated
      that the patients had a low quality of life although they received the care and
      treatments that are effective in patients with diabetes and suffering from smear
      positive PTB.

PMID- 29579432
TI  - Clinical features vary by the aetiology of meningitis in HIV seropositive
      patients: A four-year study from a tertiary hospital in India.
AB  - Meningitis is a serious infection of the nervous system associated with high
      mortality in Human Immunodeficiency Virus (HIV) seropositive individuals. Asian
      clinical studies describing meningitis in people living with HIV are scarce. We
      describe the clinical features of meningitis in 116 HIV seropositive patients
      from a tertiary hospital in India as a cross-sectional observational study. The
      mean age of the patients in our study was 35+/-9 years with 70.6% of them being
      men. Eighty-five percent of the patients had an altered sensorium during the
      illness. Tuberculous meningitis [82.6%] was the most common cause. Clinical
      features varied by aetiology. Cranial nerve deficits [40%] were common in
      Cryptococcal meningitis. Hydrocephalus [3%], infarcts [15.9%] and IntraCranial
      Space Occupying Lesions (ICSOLs) [39.1%] were common in tuberculous meningitis.

PMID- 29579433
TI  - Awareness of health care workers, patients and visitors regarding air borne
      infection control - A descriptive study from a Tertiary Care Centre in Kerala,
      southern India.
AB  - Airborne infections are major public health concern especially in hospitals and
      public spaces in a highly populated country like India. Generating awareness
      about good infection control practices among common man and health care workers
      are important steps in curtailing transmission of air borne infections. In this
      study we were trying to assess the awareness of airborne infection control
      measures among patients, bystanders and healthcare workers in a tertiary care
      hospital at Kochi, Kerala. Self-administered questionnaire which included 10
      questions for health care staff and 12 questions for lay men prepared on the
      basis of NAIC and NCDC guideline were given to the study participants. 143 health
      care staff and 332 laymen were participated in the study. In both groups majority
      of the responses were correct. However, only a small proportion of health care
      staff correctly answered fast tracking of a patient with TB (14.7%) and minimum
      air exchanges in air-conditioned settings (15.4%). Among laymen only a few
      correctly identified ideal place for sputum collection (43.3%) and role of hand
      washing in preventing flu (36.4%). Overall more intervention needed in improving
      awareness about good infection control practices among both health care staff and
      laymen.

PMID- 29579434
TI  - Localized hepatic tuberculosis presenting as severe hypercalcemia.
AB  - Hypercalcemia might present itself in association with granulomatous diseases
      such as tuberculosis. We report a rare case of a 62-year-old man with
      hypercalcemia due to hepatic tuberculosis. The diagnosis was based on
      laparoscopic and a histopathological examination. After treatment with anti
      tuberculosis medication, the patient's serum calcium levels were within normal
      limits. Tuberculosis needs to be excluded as a diagnosis in any febrile patient
      with hypercalcemia, especially in countries where tuberculosis is endemic.

PMID- 29579435
TI  - Isoniazid induced early-onset of motor dominant neuropathy and treatment with
      high dose of pyridoxine.

PMID- 29579436
TI  - Tubercular esophagocutaneous fistula: Rare case report.
AB  - Tubercular esophagocutaneous fistula is a rare entity with only about five cases
      reported so far. It can be as a result of primary involvement of esophagus by
      tuberculosis or due to spread of infection from adjacent structures like lungs or
      mediastinal lymph nodes. The fistula usually heals with initiation of
      antitubercular therapy and surgery is rarely required. Here we report a case of
      65-year-old diabetic male who developed esophagocutaneous fistula secondary to
      caseation of mediastinal lymph nodes and was successfully treated with
      antitubercular treatment.

PMID- 29579437
TI  - Intraventricular tuberculoma: An unusual presentation of brain tuberculosis.

PMID- 29579438
TI  - Retraction notice to "SRI36160 is a specific inhibitor of Wnt/<beta>-catenin
      signaling in human pancreatic and colorectal cancer cells" [Canc. Lett. 389C
      (2017) 41-48].

PMID- 29579439
TI  - Retraction notice to "A novel class of specific Hsp90 small molecule inhibitors
      demonstrate in vitro and in vivo anti-tumor activity in human melanoma cells".

PMID- 29579440
TI  - Retraction notice to "MiR-143 inhibits tumor cell proliferation and invasion by
      targeting STAT3 in esophageal squamous cell carcinoma".

PMID- 29579441
TI  - Unending Complexity in the Readmission Program.

PMID- 29579442
TI  - Will Hospital Peer Grouping by Patient Socioeconomic Status Fix the Medicare
      Hospital Readmission Reduction Program or Create New Problems?
AB  - BACKGROUND: In 2016 the U.S. Congress directed the Centers for Medicare &
      Medicaid Services (CMS) to implement the 21st Century Cures Act to fix a flaw in
      the Hospital Readmissions Reduction Program (HRRP). One section of the Act is
      intended to remove bias in calculating penalties for hospitals treating large
      percentages of low socioeconomic status (SES) patients. A study was conducted to
      analyze the effect of the introduction of SES hospital peer groups on the number
      and distribution of the hospitals being penalized. METHODS: The CMS analysis
      files for the fiscal year 2017 HRRP final rule and Disproportionate Share
      Hospital adjustments were used to assign hospital peer groups. The median excess
      readmission ratios for hospital peer groups were calculated, and the resulting
      pattern of hospital penalties within peer groups was analyzed. RESULTS: The
      findings suggest that because CMS assigns individual HRRP penalties on six
      clinical conditions but proposes to assign hospitals to a single SES peer group
      based on all admissions, it will ignore substantial differences in the
      distribution of peer group medians across these conditions. For surgical cases,
      as expected, hospitals with fewer patients had higher readmission rates, while
      for medical cases, hospitals with fewer patients had fewer readmissions. These
      findings may result in distortion of the peer group adjustment intended to
      correct for SES. CONCLUSION: Hospital peer groups may create unintended
      redistributions of penalties through distortion of peer group medians. An
      observed relationship between lower-volume hospitals and fewer readmissions for
      medical conditions requires additional research to establish its basis.

PMID- 29579443
TI  - How Patient Partners Influence Quality Improvement Efforts.
AB  - BACKGROUND: There is growing acknowledgement that patients are key stakeholders
      in improving quality of medical care, yet a key barrier to integrating patients
      into quality improvement teams (QITs) as patient partners is the lack of evidence
      of their impact. This mixed-method study was conducted to identify the ways
      patient partners influence QITs and to document the extent of patient partners'
      impact. METHODS: Focus groups and in-depth interviews were conducted with 17
      patient partners and 11 staff at WellSpan Health and Aligning Forces for Quality
      South Central Pennsylvania to identify the specific mechanisms through which
      patients influenced QIT efforts. Online surveys of 47 patient partners and 56 QIT
      leaders were conducted in summer 2016 to test the ways in which patient partners
      affected quality improvement (QI) and gauge respondents' perceptions of the
      impact of patient partners' contributions. RESULTS: Patient partners influenced
      QI through three key mechanisms: symbolism, providing feedback (on written
      material for patients and new policies), and making suggestions (on office
      communication, educational materials, physical space, and clinical care
      processes). Almost three quarters of the patient partners believed they had a
      moderate to very large impact on their QIT's QI efforts. Eight of the 10 QIT
      leaders reported that patient partners improved patient-centeredness of QI a
      "moderate amount" to a "great deal" through one of the three key mechanisms.
      CONCLUSION: Integrating patient partners into ambulatory care QITs was a largely
      positive experience for patient partners, QIT leaders, and administrators. The
      changes that patient partners prompted were meaningful and likely improved
      patients' experience with care.

PMID- 29579444
TI  - Optimizing Hospitalist-Patient Communication: An Observation Study of Medical
      Encounter Quality.
AB  - BACKGROUND: Optimizing patient-hospitalist interactions heightens patient
      satisfaction, improves patient health outcomes, and improves hospitalist job
      satisfaction. A study was conducted to recognize hospitalist communication that
      enhance encounters, identify hospitalist behaviors for improvement interventions,
      and explore the association of time and gender with communication quality.
      METHODS: Researchers observed encounters between 36 hospitalists and 206 adult
      patients. All but 1 of the hospitalists was observed at a 410-bed, general
      medical and surgical facility in the Midwest. RESULTS: On the adapted Kalamazoo
      Essential Elements of Communication Checklist (KEECC), hospitalists scored
      highest on the Builds a Relationship, Shares Information, and Gathers Information
      dimensions. Participants were seen using multiple, effective verbal and nonverbal
      techniques to show care and concern, as well as create relational rapport, often
      while successfully sharing and obtaining clinical information. Hospitalists
      scored lowest on the Understands the Patient Perspective and Reaches Agreement
      dimensions. Hospitalists were observed infrequently and inconsistently
      empathizing with patients and rarely attempting to gain shared understanding and
      agreement from patients. Significant difference was found in sharing information
      (t [194] = 2.47; p = 0.01), with male hospitalists (mean [M] = 4.14; standard
      deviation [SD] = 1.01) more highly rated than female hospitalists (M = 3.78; SD =
      0.90). Hospitalist and patient gender match revealed significant difference in
      sharing information (F [3,192] = 2.60; p = 0.05). Male hospitalists were rated
      higher interacting with female patients than female hospitalists interacting with
      male patients. CONCLUSION: Results identify specific hospitalist communication
      techniques that may ultimately contribute to better-quality medical encounters.
      Communication interventions are recommended.

PMID- 29579445
TI  - A Collaborative for Implementation of an Evidence-Based Clinical Pathway for
      Enhanced Recovery in Colon and Rectal Surgery in an Affiliated Network of
      Healthcare Organizations.
AB  - BACKGROUND: In 2015 the Mayo Clinic Care Network (MCCN), in an effort to extend
      medical knowledge and share these best practices, embarked on an education
      mission to diffuse the clinical practice redesign involving the practice of colon
      and rectal surgery at Mayo Clinic (Rochester, Minnesota) to members of the MCCN.
      They elected to use a collaborative framework in an attempt to transfer knowledge
      to multiple teams in an efficient and supportive manner. METHODS: Eight MCCN
      members assembled a multidisciplinary team, which participated in both a didactic
      learning session delivered by frontline experts, as well as follow-up remote
      sessions regarding Mayo Clinic's enhanced recovery pathway for colon and rectal
      surgery. Teams departed the group session with established immediate next steps,
      communication plans, and an awareness of potential barriers and strategies for
      mitigation. Monthly coaching calls followed in an effort to help all teams meet
      their time line and overall goals. Finally, all participants met again after six
      months to report their clinical outcomes, as well their unique individual
      organization's successes and barriers encountered. RESULTS: Participating teams
      felt overwhelmingly that the collaborative program exceeded their expectations
      and equipped them with the tools to be successful. They also felt that the
      extended support provided by the Mayo Clinic team was essential, and the
      collaboration with other members markedly enhanced their experience. Importantly,
      all teams were able to successfully reduce length of stay, which was the desired
      main clinical outcome. DISCUSSION: The collaborative format was instrumental in
      the rapid diffusion and successful implementation of a transformative practice
      redesign involving colorectal surgical care of patients.

PMID- 29579446
TI  - The Hidden Cost of Regulation: The Administrative Cost of Reporting Serious
      Reportable Events.
AB  - BACKGROUND: More than half of the 50 states (27) and the District of Columbia
      require reporting of Serous Reportable Events (SREs). The goal is to hold
      providers accountable and improve patient safety, but there is little information
      about the administrative cost of this reporting requirement. This study was
      conducted to identify costs associated with investigating and reporting SREs.
      METHODS: This qualitative study used case study methods that included
      interviewing staff and review of data and documents to investigate each SRE
      occurring at one academic medical center during fiscal year 2013. A framework of
      tasks and a model to categorize costs was created. Time was summarized and costs
      were estimated for each SRE. RESULTS: The administrative cost to process 44 SREs
      was estimated at $353,291, an average cost of $8,029 per SRE, ranging $6,653 for
      an environmental-related SRE to $21,276 for a device-related SRE. Care management
      SREs occurred most frequently, costing an average $7,201 per SRE. Surgical SREs,
      the most expensive on average, cost $9,123 per SRE. Investigation of events
      accounted for 64.5% of total cost; public reporting, 17.2%; internal reporting,
      10.2%; finance and administration, 6.0%; and 2.1%, other. Even with 26 states
      mandating reporting, the 17.2% incremental cost of public reporting is
      substantial. CONCLUSION: Policy makers should consider the opportunity costs of
      these resources, averaging $8,029 per SRE, when mandating reporting. The benefits
      of public reporting should be collectively reviewed to ensure that the
      incremental costs in this resource-constrained environment continue to improve
      patient safety and that trade-offs are acknowledged.

PMID- 29579447
TI  - Using the Patient Safety Huddle as a Tool for High Reliability.
AB  - A Patient Safety Huddle was developed at a community hospital (Providence Little
      Company of Mary Medical Center, San Pedro, California) through consultation with
      key stakeholders. The goal was to become a high reliability organization by
      improving communication across different departments, troubleshooting operational
      problems, focusing on safety and quality metrics, and reporting unusual
      occurrences. The Patient Safety Huddle involved executives in development and
      implementation, respect for employee time, ensuring accountability, and
      empowering frontline staff to foresee and deal with safety issues. The current
      template of the Patient Safety Huddle agenda and the Documentation Tools used to
      address patient safety issues are provided.

PMID- 29579449
TI  - Basidiomycete Genomics.

PMID- 29579448
TI  - Improving Satisfaction with Pediatric Pain Management by Inviting the
      Conversation.
AB  - BACKGROUND: Patient satisfaction with pain management is associated with improved
      patient adherence to medical management and efficient service utilization.
      Pediatric pain control is challenging, given the inability to elicit reliable
      histories, particularly in younger patients. Several studies have suggested that
      communication surrounding pain management can improve satisfaction, although
      there are limited data describing structured interventions with measurable
      outcomes. A quality improvement project was conducted to determine if reliably
      asking families about pain management was associated with improved patient
      satisfaction with pain management. METHODS: In an academic pediatric hospital,
      nurse manager rounds were used to invite a conversation about pain management.
      The question, "Pain management is very important to us. Has your child's pain
      been well controlled?" was added to the established standard questions asked
      during nurse manager rounds. Effectiveness was measured using the preexisting
      Press Ganey survey question, "How well was your child's pain controlled?"
      Responses were compared between those patients who were and were not exposed to
      the rounding question. RESULTS: Data for 1,032 patients were used to establish
      baseline satisfaction with pain management scores. In the intervention period,
      328 patients received nurse manager rounds and 121 did not. The median of the
      weighted mean patient survey satisfaction scores were baseline, 91.5%; receiving
      intervention, 94.2%; and not receiving intervention, 90.0%. Patients who received
      the intervention reported higher satisfaction with pain management than those who
      did not (p <0.0001). CONCLUSION: Hospitals seeking to improve satisfaction with
      pain management should encourage health care providers to reliably discuss pain
      control with pediatric patients.

PMID- 29579450
TI  - Introduction to Virology special issue featuring nidovirus research.

PMID- 29579451
TI  - Introducing . . . FAST TRACK.

PMID- 29579452
TI  - Research Techniques Made Simple: Two-Photon Intravital Imaging of the Skin.
AB  - Over the last few years, intravital two-photon microscopy has matured into a
      powerful technology helping basic and clinical researchers obtain quantifiable
      details of complex biological mechanisms in live and intact tissues. Two-photon
      microscopy provides high spatial and temporal resolution in vivo with little
      phototoxicity that is unattainable by other optical tools like confocal
      microscopy. Using ultrashort laser pulses, two-photon microscopy allows the
      visualization of molecules, cells, and extracellular structures up to depths of 1
      mm within tissues. Consequently, real-time imaging of the individual skin layers
      under both physiological and pathological conditions has revolutionized our
      understanding of cutaneous homeostasis, immunity, and tumor biology. This review
      provides an overview to two-photon microscopy of the skin by covering the basic
      concepts and current applications in diverse preclinical and clinical settings.

PMID- 29579453
TI  - Survival of Second-Line Biologics in Psoriasis: The British BADBIR Registry Data
      Informs Daily Practice.
AB  - Psoriasis is one of the most chronic diseases in dermatology. Only a small
      percentage of patients ever experience relapse-free survival. The constant
      presence of plaques and comorbidities that affect the cardiovascular system,
      joints, and other organs greatly impair patients' quality of life. In addition,
      the life expectancy of psoriatic patients is shortened by several years. Hence,
      long-term and ideally systemic treatment with minimal adverse effects may be
      warranted.

PMID- 29579454
TI  - A Fibroblast Is Not a Fibroblast Is Not a Fibroblast.
AB  - Fibrosis after injury is a huge public health concern, leading to morbidity,
      mortality, and expenditure of billions of health care dollars. Recent mouse
      studies have shown that dermal fibroblasts are heterogeneous. New research using
      single-cell RNA sequencing to identify major fibroblast populations in humans is
      paving the way to a better understanding of fibroblast heterogeneity and
      fibrosis.

PMID- 29579455
TI  - Topical Gentamicin for the Treatment of Genetic Skin Diseases.
AB  - Clinical application of topical gentamicin is a worthwhile option to investigate
      further for Nagashima-type palmoplantar keratosis and other genetic skin diseases
      caused by nonsense mutations. It is especially interesting to study gentamicin 1B
      because it may be more efficacious than other gentamicin components. Topical
      gentamicin has an acceptable safety profile, although prospective tracking of
      antibiotic resistance is warranted.

PMID- 29579456
TI  - Targeting the Plasticity of Psoriasis.
AB  - Psoriasis is a common inflammatory condition found in 1-2% of the population. The
      greatest advances in psoriasis treatment have occurred in patients with severe
      psoriasis, moving from systemic small molecules including methotrexate,
      cyclosporine, and retinoids to targeted agents against psoriasis-associated
      cytokines, such as TNF-alpha, IL-12, IL-23, and IL-17. Although the new biologics
      do not have the same adverse effects as the systemic drugs, they do predispose to
      systemic infections (and perhaps cancer), and they are extremely expensive. The
      focus on biologic therapies has been accompanied by a relative neglect of small
      molecules, which can be used either topically or systemically. No small molecule
      has been able to compete significantly with topical glucocorticoids, the mainstay
      of treatment for mild to moderate psoriasis for more than half a century.

PMID- 29579458
TI  - Addendum.

PMID- 29579457
TI  - A Modeling Conundrum: Murine Models for Cutaneous Wound Healing.
AB  - The complexity of the cutaneous wound healing process and its impairment in
      disease states, combined with the urgent clinical need for new therapies demand
      well-defined preclinical models that facilitate translation of research findings
      to clinical use. Many murine wound models are well suited for studying mechanisms
      of various aspects of wound healing, but they have shown limited utility for
      translating research findings to human conditions, thereby impeding therapeutic
      developments. Ansell et al. underscore the need for standardization of
      preclinical murine models by showing the impact of duration of diabetes, animal
      sex, and assessment methods on healing outcomes in the streptozotocin-induced
      diabetes mellitus rat model. Recognizing and understanding the limitations and
      advantages of preclinical murine wound models will facilitate more effective
      translation of experimental results to improved treatment of human chronic
      wounds.

PMID- 29579459
TI  - SnapshotDx Quiz: April 2018.

PMID- 29579461
TI  - The 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial
      Diseases, in Collaboration With the European Society for Vascular Surgery (ESVS).

PMID- 29579460
TI  - Cells to Surgery Quiz: April 2018.

PMID- 29579462
TI  - Successful Percutaneous Embolization of an Iatrogenic Pulmonary Artery Defect
      through a Chest Drain: A Novel Extravascular Approach (Inside-Out Plug
      Technique).

PMID- 29579464
TI  - Arterial Injury During Bone Marrow Aspiration: Embolization through the Biopsy
      Needle.

PMID- 29579463
TI  - Extrahepatic Collateral Artery Extravasation in Patients with Ruptured
      Hepatocellular Carcinoma.
AB  - This report describes 3 patients with previously untreated hepatic tumors who
      underwent embolization for the treatment of extravasation from extrahepatic
      arteries. Although development of extrahepatic collateral blood supply is well
      known, its importance in the presentation of rupture of liver tumors may be
      underrecognized. Findings that suggest bleeding from extrahepatic arteries
      include a discrepancy in the pattern of extravasation on computed tomography vs
      hepatic angiography and a lack of stabilization of vital signs after embolization
      of hepatic arteries. To achieve successful hemostasis in embolization, the
      potential involvement of such extrahepatic arteries should be accurately
      recognized, suggestive imaging findings considered, and the occult vessels
      selected and embolized.

PMID- 29579465
TI  - Re: Immuno-oncology and Its Opportunities for Interventional Radiologists: Immune
      Checkpoint Inhibition and Potential Synergies with Interventional Oncology
      Procedures.

PMID- 29579467
TI  - Erratum.

PMID- 29579466
TI  - Reply to: "Re: Immuno-oncology and Its Opportunities for Interventional
      Radiologists: Immune Checkpoint Inhibition and Potential Synergies with
      Interventional Oncology Procedures".

PMID- 29579468
TI  - Invited commentary.

PMID- 29579469
TI  - Invited commentary.

PMID- 29579470
TI  - Invited commentary.

PMID- 29579471
TI  - Invited commentary.

PMID- 29579472
TI  - The use of smartphone-attached thermography camera in diagnosis of acute lower
      limb ischemia.

PMID- 29579473
TI  - Intraoperative insertion of paravertebral catheter for postoperative analgesia in
      retroperitoneal aortic aneurysm repair.
AB  - Paravertebral catheters are a well-established analgesic modality in thoracic
      surgery but have not been described in abdominal aortic surgery. We describe a
      simple, safe, and effective technique of paravertebral catheter insertion by the
      operative surgeon after a retroperitoneal abdominal aortic aneurysm repair. Once
      the aneurysm repair is complete, an extrapleural plane between the parietal
      pleura and the twelfth rib is created through blunt dissection. A catheter is
      advanced into the space percutaneously under direct vision, and a continuous
      infusion of local anesthetic is administered. Paravertebral catheters typically
      remain in place for 3 to 5 days and provide excellent postoperative non-narcotic
      analgesia.

PMID- 29579474
TI  - MIPS cost measures for 2018.

PMID- 29579475
TI  - Reply.

PMID- 29579476
TI  - Regarding "Incidence and risk factors of groin lymphocele formation after
      venoarterial extracorporeal membrane oxygenation in cardiogenic shock patients".

PMID- 29579477
TI  - 1-C-phosphonomethyl- and 1-C-difluorophosphonomethyl-1,4-imino-l-arabinitols as
      Galf transferase inhibitors: A comparison.
AB  - The convenient preparation of iminopentitol derivatives, based on a 1,4-dideoxy
      1,4-imino-l-arabinitol scaffold carrying beta-phosphono(difluoromethyl) or beta
      phosphonomethyl appendages, as Galf-1P mimics, is reported. The compounds were
      tested for their ability to inhibit GlfT2, a vital galactofuranosyltransferase
      involved in the cell wall biosynthesis of mycobacteria. Interestingly, the Galf
      1P mimics lacking a fluorine atom (7 and 8) were very poor inhibitors, showing
      less than 20% inhibition of GlfT2, whereas compounds 2 and 3, which contains a
      difluoromethylenephosphonate moiety were more potent inhibitors. Compound 3 that
      is fully deprotected was the most potent showing a significant IC50 value (0.9
      mm), despite the absence of the diphosphate linkage present in the parent sugar
      nucleotide. This study paves the way to the synthesis of more complex beta
      phosphonomethyl-imino-l-arabinitol derivatives as simplified mimics of UDP-alpha
      d-Galf.

PMID- 29579478
TI  - Surgical resection versus systemic therapy for breast cancer liver metastases:
      Results of a European case matched comparison.
AB  - BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with
      systemic treatment is increasingly accepted but not offered as therapeutic
      option. New evidence of the additional value of surgery in these patients is
      scarce while prognoses without surgery remains poor. PATIENTS AND METHODS: For
      this case matched analysis, all nationally registered patients with BCLM confined
      to the liver in the Netherlands (systemic group; N = 523) were selected and
      compared with patients who received systemic treatment and underwent hepatectomy
      (resection group; N = 139) at a hepatobiliary centre in France. Matching was
      based on age, decade when diagnosed, interval to metastases, maximum metastases
      size, single or multiple tumours, chemotherapy, hormonal or targeted therapy
      after diagnosis. Based on published guidelines, palliative systemic treatment
      strategies are similar in both European countries. RESULTS: Between 1983 and
      2013, 3894 patients were screened for inclusion. Overall median follow-up was 80
      months (95% CI 70-90 months). The median, 3- and 5-year overall survival of the
      whole population was 19 months, 29% and 19%, respectively. The resection and
      systemic group had median survival of 73 vs. 13 months (P < 0.001), respectively.
      Three and 5-year survival was 18% and 10% for the systemic group and 75% and 54%
      for the resection group, respectively. After matching, the resection group had a
      median overall survival of 82 months with a 3- and 5-year overall survival of 81%
      and 69%, respectively, compared with a median overall survival of 31 months in
      the systemic group with a 3- and 5-year overall survival of 32% and 24%,
      respectively (HR 0.28, 95% CI 0.15-0.52; P < 0.001). CONCLUSIONS: For patients
      with BCLM, liver resection combined with systemic treatment results in improved
      overall survival compared to systemic treatment alone. Liver resection should be
      considered in selected cases.

PMID- 29579479
TI  - Editorial: Special issue on advances in biomedical image processing.

PMID- 29579480
TI  - Can white-rot fungi be a real wastewater treatment alternative for organic
      micropollutants removal? A review.
AB  - Micropollutants are a diverse group of compounds that are detected at trace
      concentrations and may have a negative effect on the environment and/or human
      health. Most of them are unregulated contaminants, although they have raised a
      concern in the scientific and global community and future regulation might be
      written in the near future. Several approaches have been tested to remove
      micropollutants from wastewater streams. In this manuscript, a focus is placed in
      reactor biological treatments that use white-rot fungi. A critical review of
      white-rot fungal-based technologies for micropollutant removal from wastewater
      has been conducted, several capabilities and limitations of such approaches have
      been identified and a range of solutions to overcome most of the limitations have
      been reviewed and/or proposed. Overall, this review argues that white-rot fungal
      reactors could be an efficient technology to remove micropollutants from specific
      wastewater streams.

PMID- 29579481
TI  - Understanding and alleviating maternal postpartum distress: Perspectives from
      first-time mothers in Australia.
AB  - BACKGROUND: Numerous factors have been shown to cause (or alleviate) maternal
      psychological distress in the early postpartum period, and a variety of
      interventions have been developed with the goal of preventing and/or managing
      such distress. However, only a few studies have explored new mothers'
      perspectives on the sources of their distress in the first six months' postpartum
      alongside the researchers' recommendations for interventions to address those
      sources. OBJECTIVES: The aim of this work was to (a) identify factors associated
      with normative psychological distress in the first 6-months' postpartum by
      healthy Australian first-time mothers, and (b) outline practical methods-rooted
      in those factors-deemed to be effective for preventing maternal psychological
      distress. METHOD: Semi-structured interviews with 32 first-time mothers and
      thematic content analysis. RESULTS: Factors associated with maternal
      psychological distress emerged in relation to cognitive, behavioural, baby, and
      social factors. Mothers also indicated that interventions targeting reductions in
      psychological distress should include education-for mothers and significant
      others-prior to the postpartum period. These interventions should be delivered by
      credible information sources (e.g. other mothers, child-health nurses) and should
      focus on confidence-enhancement and social support provision. CONCLUSION: As well
      as reinforcing evidence regarding common postpartum stressors, this study
      revealed novel insight into issues associated with normative psychological
      distress for new mothers (e.g., self-compassion). Perhaps most significant was
      that mothers also identified a range of clear practical strategies for community
      based intervention designs that target psychological distress. As a result, these
      findings provide guidelines for interventions aimed at reducing psychological
      distress in the early postpartum period for Australian mothers.

PMID- 29579482
TI  - Effect of recorded maternal voice, breast milk odor, and incubator cover on pain
      and comfort during peripheral cannulation in preterm infants.
AB  - PURPOSE: This study was conducted to assess the effect of recorded maternal
      voice, breast milk odor, and incubator cover on the pain and comfort of preterm
      infants during peripheral cannulation. METHODS: This study was a randomized
      controlled trial. The sample of the study included 136 preterm infants who met
      the case selection criteria. The infants were randomly assigned to different
      groups. DATA COLLECTION TOOL: In the study, a recorded maternal voice was played
      to the maternal voice group. The breast milk odor group was exposed to the odor
      of breast milk. The incubator cover group was covered by using an incubator cover
      before, during, and after the peripheral cannulation procedure on the infants in
      the experimental group. RESULT: While no difference was observed between the
      groups before the peripheral cannulation procedure in terms of the total
      Premature Infant Pain Profile (PIPP) scores, a significant difference existed
      between the PIPP scores during and after the procedure. This difference was due
      to the incubator cover group. CONCLUSION: Breast milk odor, recorded maternal
      voice, and incubator cover in preterm infants are recommended as simple, safe,
      and supportive stimuli that facilitate positive effects during painful
      procedures.

PMID- 29579483
TI  - Deliberate practice and nurse competence.
AB  - BACKGROUND: Increasing demand for accountability in health care requires that we
      understand how nurses continually increase their expertise. Development of
      expertise has been linked to deliberate practice in many domains but little is
      known about how deliberate practice impacts the expertise of registered nurses.
      OBJECTIVES: Evaluate the relationships among experience, education, deliberate
      practice, and competence as an empirical referent of expertise, and to identify
      which of the independent variables makes the highest contribution to competence.
      METHODS: Cross-sectional, descriptive, correlational study design was used. A
      purposive sample of RNs from one large, Midwestern teaching hospital was
      surveyed. RESULTS: After taking into consideration demographic variables,
      education and experience, deliberate practice made the greatest contribution to
      competence. No significant relationship was found between years of experience or
      education and competence. CONCLUSION: This study provides empirical evidence for
      the relationship of deliberate practice to competence, a promising concept for
      explaining the development of skill acquisition in nursing.

PMID- 29579484
TI  - Patient-controlled oral analgesia for acute abdominal pain: A before-and-after
      intervention study on pain intensity and use of analgesics.
AB  - AIM: To compare the use of patient-controlled oral analgesia with nurse
      controlled analgesia for patients admitted to hospital with acute abdominal pain.
      The primary outcome measure was pain intensity. The secondary outcome measures
      were the use of analgesics and antiemetics. BACKGROUND: Inadequate pain
      management of patients with acute abdominal pain can occur during hospital
      admission. Unrelieved acute pain can result in chronic pain, stroke, bleeding and
      myocardial ischemia. METHODS: A before-and-after intervention study was conducted
      in an emergency department and a surgical department with three subunits. Data
      were collected from medical charts and analyzed using chi-squared and Kruskal
      Wallis tests. RESULTS: A total of 170 patients were included. The median pain
      intensity score, using the numeric ranking scale, was 2.5 and 2 on Day 2 (p =
      0.10), 2 and 2 on Day 3 (p = 0,40), 2.5 and 0 on Day 4 (p = 0.10), 2 and 0 on Day
      5 (p = 0.045) in the control and intervention group, respectively. The percentage
      of patients receiving analgesics was 93 and 86 on Day 2 (p = 0.20), 91 and 75 on
      Day 3 (p = 0.02), 89 and 67 on Day 4 (p = 0.009) and 80 and 63 on Day 5 (p =
      0.39). The use of antiemetics was similar in the two groups. CONCLUSION: Patient
      controlled oral analgesia significantly reduced the numerical ranking pain scale
      score on Day 5 and the consumption of analgesics on Days 3 and 4 after hospital
      admission. Patient-controlled oral analgesia is feasible as pain management for
      patients, but only with minor impact on experienced pain intensity and use of
      analgesics.

PMID- 29579485
TI  - Nurses, age, job demands and physical activity at work and at leisure: A cross
      sectional study.
AB  - BACKGROUND: The nursing workforce is ageing and increased age and demands at
      work, can impact on physical activity levels in the workplace and at leisure.
      Research has shown that work physical activity, without activity at leisure, is
      insufficient to prolong well-being. This study investigated the physical activity
      levels of a sample of nurses and aimed to determine if age and job demands are
      associated with engaging in recommended physical activity levels at work and at
      leisure. METHODS: A cross-sectional study was conducted with data collected
      during 2016. Two-hundred and ten nurses participated in the study. Two validated
      instruments were used: the Copenhagen Psychosocial Questionnaire (quantitative
      and cognitive demands) and the International Physical Activity Questionnaire.
      RESULTS: Older nurses (>=40-years) were significantly less likely to report
      engaging in recommended physical activity levels at work than younger nurses [OR
      0.47, 95% CI (0.25-0.88) p = 0.02]. Nurses with high quantitative demands were
      over twice as likely to engage in recommended levels of physical activity at work
      and at leisure. Engaging in recommended levels of physical activity at work was
      not associated with leisure-time physical activity reports. CONCLUSION:
      Initiatives need to be put in place to ensure older nurses can fulfil their
      nursing role within their capabilities. These could include offering personal
      physical activity education to both on and off-duty nurses. Assessment of ability
      and patient acuity may be necessary.

PMID- 29579486
TI  - Incidence and risk factors of workplace violence against nurses in a Chinese top
      level teaching hospital: A cross-sectional study.
AB  - PURPOSE: To investigate the incidence of workplace violence involving nurses and
      to identify related risk factors in a high-quality Chinese teaching hospital.
      METHODS: A cross-sectional study design was used. The final sample comprised
      responses from 1831 registered nurses collected with a whole-hospital survey from
      June 1 to June 15, 2016. The demographic characteristics of the nurses who had
      experienced any form of violence were collected, and logistic regression analysis
      was applied to evaluate the risk factors for nurses related to workplace
      violence. RESULTS: Out of the total number of nurses surveyed, 904 (49.4%) nurses
      reported having experienced any type of violence in the past year. The
      frequencies of exposure to physical and non-physical violence were 6.3% (116) and
      49.0% (897), respectively. All the incidence rates of violence were lower than
      those of other studies based on regional hospitals in China and were at the same
      level found in developed countries and districts. Binary logistic regression
      analysis revealed that nurses at levels 2 to 4 and female nurses in clinical
      departments were the most vulnerable to non-physical violence. For physical
      violence, the two independent risk factors were working in an emergency
      department and having 6-10 years of work experience. CONCLUSIONS: Workplace
      violence directly threatens nurses from high-quality Chinese teaching hospitals.
      However, the incidence of WPV against nurses in this teaching hospital was better
      than that in regional hospitals. This study also provides reference material to
      identify areas where nurses encounter relatively high levels of workplace
      violence in high-quality Chinese teaching hospitals.

PMID- 29579487
TI  - Factors affecting the delivery of healthcare on a humanitarian operation in West
      Africa: A qualitative study.
AB  - INTRODUCTION: Medical personnel in the UK Armed Forces are highly trained to
      deploy in support of military operations that assist humanitarian, peacekeeping,
      counter-terrorism and environmental catastrophes anywhere in the world. Such
      environments are often austere and successful outcomes demand an individual is
      highly resilient and able to adapt quickly to any situation. This qualitative
      study aimed to determine the factors that affect healthcare delivery on such
      missions by capturing the personal experiences of the first military personnel
      deployed on a humanitarian operation in support of the Ebola outbreak in West
      Africa between October 2014 and January 2015. METHODS: A grounded theory
      methodology was utilised to probe the personal accounts of these experiences.
      Semi-structured interviews were conducted on 14 multi-disciplinary personnel 3-6
      months following their return to the UK and were transcribed verbatim. Data were
      analysed and a framework generated that had been further refined by discussion
      with military personnel independent of the study but with the contextual
      understanding and experience of this particular deployment. FINDINGS: The
      resultant theoretical framework was underpinned by participants framing their
      experience by "just getting on with it". Stressors such as a poor flow of
      information, a fear of the unknown, strict patient admission criteria,
      environmental constraints and transcultural boundaries to care were mitigated by
      strong leadership, teamwork, peer support and the positive impact of having made
      a difference. CONCLUSION: Collective pre-deployment training generated
      competence, confidence and team cohesiveness providing a firm foundation for
      coping with the challenges of this humanitarian mission, which continued to be
      strengthened throughout the deployment. These factors helped to build personnel's
      resilience to the stressors associated with the mission and may help to protect
      their mental health outcomes in the longer-term.

PMID- 29579488
TI  - Relationships between public health nurse-delivered physical activity
      interventions and client physical activity behavior.
AB  - AIM: The purpose of this study was to identify physical activity interventions
      delivered by public health nurses (PHNs) and examine their association with
      physical activity behavior change among adult clients. BACKGROUND: Physical
      activity is a public health priority, yet little is known about nurse-delivered
      physical activity interventions in day-to-day practice or their outcomes.
      METHODS: This quantitative retrospective evaluation examined de-identified
      electronic-health-record data. Adult clients with at least two Omaha System
      Physical activity Knowledge, Behavior, and Status (KBS) ratings documented by
      PHNs between October 2010-June 2016 (N=419) were included. Omaha System baseline
      and follow-up Physical activity KBS ratings, interventions, and demographics were
      examined. RESULTS: Younger clients typically receiving maternal-child/family
      services were more likely to receive interventions than older clients (p<0.001).
      A total of 2869 Physical activity interventions were documented among 197
      clients. Most were from categories of Teaching, Guidance, Counseling (n=1639) or
      Surveillance (n=1183). Few were Case Management (n=46). Hierarchical regression
      modeling explained 15.4% of the variance for change in Physical activity Behavior
      rating with significant influence from intervention dose (p=0.03) and change in
      Physical activity Knowledge (p<0.001). CONCLUSION: This study identified and
      described physical activity interventions delivered by PHNs. Implementation of
      department-wide policy requiring documentation of Physical activity assessment
      for all clients enabled the evaluation. A higher dose of physical activity
      interventions and increased Physical activity knowledge were associated with
      increased Physical activity Behavior. More research is needed to identify factors
      influencing who receives interventions and how interventions are selected.

PMID- 29579489
TI  - First-time fathers' health status during the perinatal period.
AB  - BACKGROUND: For first-time fathers, the perinatal period is a critical period of
      stress and imbalance. Marital intimacy and social support may affect their stress
      and health status while they change their roles. AIM: This study was to explore
      the changes of and correlations among marital intimacy, social support, and
      health status and predictors of first-time fathers' health status during the
      perinatal period. METHODS: With a repeated measures study design, a total of 217
      first-time fathers whose spouses were in the third trimester of pregnancy were
      recruited for the study. The Chinese Health Questionnaire, Marital Intimacy
      Scale, and Social Support Scale were employed to collect data at a medical center
      in the 36th week of pregnancy and the 1st and 4th weeks after childbirth.
      RESULTS: The levels of marital intimacy and social support of first-time fathers
      during the perinatal period increased significantly with time. Meanwhile, the
      period of the first week after childbirth was a predictor of first-time father's
      health status. CONCLUSIONS: This study only tracked the first-time fathers'
      health status in the 36th week of pregnancy and the 1st and 4th weeks after
      childbirth. Future studies could track them until one year after childbirth in
      order to explore the impact of the perinatal period on the couples and their
      babies. During the perinatal period, health care providers shall assess and
      provide needed interventions to first-time fathers as soon as possible to
      facilitate the first-time fathers to get ready for the role transition and to
      promote their health status.

PMID- 29579490
TI  - Evaluating a psychosocial intervention for men with prostate cancer and their
      partners: Outcomes and lessons learned from a randomized controlled trial.
AB  - AIM: This study evaluated the process and outcome of a psychosocial intervention
      for men with prostate cancer and their partners. As more men survive prostate
      cancer, they and their partners need help and support to help them cope with the
      physical and psychosocial effects of the disease and treatment. There is a lack
      of psychosocial interventions for men with prostate cancer and their partners.
      METHODS: A randomized controlled trial was conducted with 34 participants to
      measure the effects of the intervention on selected psychosocial outcomes, post
      intervention and at one month' follow-up. The nine-week program (CONNECT)
      consisted of three group and two telephone sessions. It focused on symptom
      management, sexual dysfunction, uncertainty management, positive thinking and
      couple communication. The outcomes, measured by validated tools were: self
      efficacy, quality of life, symptom distress, communication, uncertainty and
      illness benefits. RESULTS: The men in the intervention group did better on two
      outcomes (communication and support) than controls. Partners in the intervention
      group did better than controls on most outcomes. Less participants than expected
      participated in the trial. The reasons for non-participation included partners
      not wishing to participate, men not interested in group work, and not
      understanding the core purpose of the intervention. The cost of training
      facilitators and for delivering the intervention appeared to be low. CONCLUSION:
      The knowledge generated from this study will be beneficial for all those
      grappling with the challenges of developing, implementing and evaluating complex
      psychosocial interventions. This study has also highlighted the difficulties in
      recruiting men and their partners in clinical trials.

PMID- 29579491
TI  - Evaluation of an assessment instrument for a sexual health curriculum for nurses
      and midwifery students in Tanzania: The sexual health education for professionals
      scale (SHEPS).
AB  - We assessed the structure and content of a new scale, the SHEPS, to assess change
      in sexual health confidence, knowledge and attitudes in nursing and midwifery
      students following an intervention (a 2-day standardized workshop on sexual
      health). Students were 78 Tanzanian nursing and midwifery students attending a
      University of Health Sciences, who were assessed immediately before and after the
      workshop on matched pre- and post-workshop questionnaires. Data confirmed
      significant changed pre- and post-test on knowledge and confidence on topics
      taught in the workshop, with the effect also extending to some topics not or
      minimally covered, suggesting that there was a general increase in confidence and
      a perception of increased knowledge following the workshop. There was power to
      detect differences even with a moderate sized matched sample. Correlations
      between knowledge and confidence on the same content items were between 0.52 and
      0.63, suggesting that respondents could clearly distinguish between knowledge and
      confidence. There were no significant differences pre- and post-test on several
      controversial cultural and religious attitudes including on abortion and non
      vaginal penetrative sex. Alpha coefficients were 0.93 for pre-test and 0.90 for
      post-test. This field test demonstrates the preliminary appropriateness of the
      SHEPS as a tool for evaluating sexual health interventions in health care
      workers.

PMID- 29579492
TI  - Palliative sedation and moral distress: A qualitative study of nurses.
AB  - BACKGROUND: Clinical nursing practice may involve moral distress, which has been
      reported to occur frequently when nurses care for dying patients. Palliative
      sedation is a practice that is used to alleviate unbearable and refractory
      suffering in the last phase of life and has been linked to distress in nurses.
      AIM: The aim of this study was to explore nurses' reports on the practice of
      palliative sedation focusing on their experiences with pressure, dilemmas and
      morally distressing situations. METHODS: In-depth interviews with 36 nurses
      working in hospital, nursing home or primary care. RESULTS: Several nurses
      described situations in which they felt that administration of palliative
      sedation was in the patient's best interest, but where they were constrained from
      taking action. Nurses also reported on situations where they experienced pressure
      to be actively involved in the provision of palliative sedation, while they felt
      this was not in the patient's best interest. The latter situation related to (1)
      starting palliative sedation when the nurse felt not all options to relieve
      suffering had been explored yet; (2) family requesting an increase of the
      sedation level where the nurse felt that this may involve unjustified hastening
      of death; (3) a decision by the physician to start palliative sedation where the
      patient had previously expressed an explicit wish for euthanasia. CONCLUSIONS:
      Nurses experienced moral distress in situations where they were not able to act
      in what they believed is the patient's best interest. Situations involving moral
      distress require nurses to be well informed and able to adequately communicate
      with suffering patients, distressed family and physicians.

PMID- 29579493
TI  - Missed Nursing Care: Research on Interventions?

PMID- 29579494
TI  - Evaluation of bedside shift report: A research and evidence-based practice
      initiative.
AB  - This evaluation of bedside shift report describes the process of involving
      clinical nurses in evidence-based practice (EBP) and research at an academic
      medical center by using existing structures and resources. Nurse involvement and
      study findings are described from idea inception to asking the clinical question,
      searching and synthesizing literature, collecting and analyzing data,
      interpreting results, and deriving conclusions. Study findings and conclusions
      demonstrate that nurses' active participation in a clinical relevant project
      promotes implementation and integration of EBP and research in the practice
      setting.

PMID- 29579495
TI  - Canadian hospital nurses' roles in communication and decision-making about goals
      of care: An interpretive description of critical incidents.
AB  - BACKGROUND: Nurses in acute medical units are uniquely positioned to support
      goals of care communication. Further understanding of nurse and physician
      perceptions about hospital nurses' actual and possible roles was required to
      improve goals of care communication. OBJECTIVE: To critically examine nurse and
      physician perceptions of the nurse's role in communication with seriously ill
      patients and their families. DESIGN: We focus on the qualitative component of a
      mixed method study. We employed an interpretive descriptive approach informed by
      Flanagan's critical incident technique. SETTINGS: Participants were recruited
      from the acute medical units at three tertiary care hospitals in three Canadian
      provinces. PARTICIPANTS: Thirty participants provided interviews (10 from each
      site): 12 nurses, 9 staff physicians and 9 medical resident physicians. METHODS:
      Participants' described "critical incidents" they considered as "excellent" or
      "poor" or "usual" practice. Interviews, were audiotaped and transcribed. Team
      based analysis used constant comparison and triangulation to identify healthcare
      team members' roles in goals of care communication. RESULTS: We identified two
      major themes from 120 critical incidents: 1) the ambiguous nature of the nurse's
      role in formal, physician-led, decision-making communication, and 2) embedded in
      care serious illness communication. Physicians understood nurses' supportive role
      in relation to their own communication practices that culminated in decisions
      about care; nurses' reported their roles were determined by unit routines,
      physician practices and preferences, and their self-confidence in supporting
      decision-making. Nurses described their unique role in facilitating informal and
      spontaneous communication with patients and families that was critical background
      work to physician-led goals of care communication. CONCLUSIONS: Nurses and
      physicians had different understandings, practices and beliefs about goals of
      care communication The value of nurses embedded in care work is key to supporting
      the interprofessional team's work during formal goals of care communication.

PMID- 29579496
TI  - Effects of bathing interval on skin condition and axillary bacterial colonization
      in preterm infants.
AB  - AIM: The objective of this study was to evaluate the effects of preterm infant
      bathing periods on skin condition and axillary skin colonization. BACKGROUND:
      Reducing the frequency of bathing in preterm infants is beneficial in reducing
      the risk of hypothermia and exposure to stress from frequent nursing contacts.
      METHODS: The subjects of this study were observed at The V hospital at the C
      University in South Korea between December 2012 and August 2013. A total of 32
      preterm infants were included and were randomly assigned to two different bathing
      intervals; every four days (n=16) and the other every two days (n=16) bathing
      groups. A neonatal skin conditions were assessed on a daily basis, whereas,
      axillary skin colonization was measured every eight days before bathing. Data was
      analyzed via the SPSS program with a non-inferiority test, t-test, chi-square
      test, Fisher's exact test, and paired t-test. RESULTS: Mean differences of skin
      condition between the four-day bathing and two-day bathing groups were 0.065 and
      the 97.5% one-sided confidence limit was 0.196 (less than the non-inferiority
      margin, 0.3). There were no statistically significant differences in skin
      condition and axillary skin colonization between the two groups (p>0.05).
      CONCLUSION: The interval of bathing for preterm infants can be changed from every
      two days to every four days without increasing the incidence of skin condition
      problems or axillary skin colonization. Less-frequent bathing may decrease the
      chance of physiological instability caused by the caring process, while providing
      them with a better environment for growth and development.

PMID- 29579497
TI  - The perceptions of patient safety culture: A difference between physicians and
      nurses in Taiwan.
AB  - AIMS: In order to pursue a better patient safety culture and provide a superior
      medical service for patients, this study aims to respectively investigate the
      perceptions of patient safety from the viewpoints of physicians and nurses in
      Taiwan. BACKGROUND: Little knowledge has clearly identified the difference of
      perceptions between physicians and nurses in patient safety culture.
      Understanding physicians and nurses' attitudes toward patient safety is a
      critical issue for healthcare organizations to improve medical quality. METHODS:
      Confirmatory factor analysis (CFA) is used to verify the structure of data (e.g.
      reliability and validity), and Pearson's correlation analysis is conducted to
      demonstrate the relationships among seven patient safety culture dimensions.
      RESULTS: Research results illustrate that more teamwork is exhibited among team
      members, the more safety of a patient is committed. Perceptions of management and
      emotional exhaustion are important components that contribute to a better patient
      safety. More importantly, working conditions and stress recognition are found to
      be negatively related from the perceptions of nurses. Compared to physicians,
      nurses reported higher stress and challenges which result from multi-task working
      conditions in the hospital. CONCLUSIONS: This study focused on the contribution
      of a better patient safety culture from different viewpoints of physicians and
      nurses for healthcare organizations in Taiwan. A different attitudes toward
      patient safety is found between physicians and nurses. The results enable the
      hospital management to realize and design appropriate implications for hospital
      staffs to establish a better patient safety culture.

PMID- 29579498
TI  - Factors associated with psychological distress amongst outpatient chemotherapy
      patients: An analysis of depression, anxiety and stress using the DASS-21.
AB  - AIM: This study sought to identify clinical, demographic and service-related
      factors associated with psychological distress amongst outpatient chemotherapy
      patients. BACKGROUND: Distress in cancer patients leads to increased risk of
      psychological comorbidity, contributing to sub-optimal treatment adherence and
      potentially leading to poorer health outcomes. Screening and recognition of
      distress and risk factors is an important aspect of holistic care within a
      multidisciplinary team environment. METHODS: Data were obtained via survey and
      chart review of ambulatory chemotherapy patients at three public tertiary
      referral hospitals in Perth, Western Australia. The DASS-21 was used to screen
      for psychological distress. Regression analyses were used to assess the
      relationship between distress and a range of cancer, socioeconomic and treatment
      factors. RESULTS: Patients with a Karnofsky Performance Score<=80 (OR 3.8, 95% CI
      [1.7, 78.7]) and average waiting time (between oncology outpatient appointment
      and commencement of chemotherapy infusion) >60min (OR 2.4, 95% CI [1.04, 5.5])
      were at increased risk of moderate-severe distress. Patients with a household
      income between $AU 50-75,000 p.a. had a lower risk of distress compared to
      <$25,000 p.a. (OR 0.05, 95% CI [0.01, 0.52]). On sub-scale analysis, depression
      and anxiety contributed more to overall distress than the stress subscales.
      CONCLUSIONS: Performance status, waiting times and household income were key
      predictors of distress. Findings could assist clinicians to identify higher-risk
      population subsets that could benefit from targeted screening and additional
      psychological and social work support. Findings could also assist administrators
      to consider the contribution of modifiable factors such as waiting times to
      patient distress.

PMID- 29579499
TI  - Using narrative intervention for HPV vaccine behavior change among Khmer mothers
      and daughters: A pilot RCT to examine feasibility, acceptability, and preliminary
      effectiveness.
AB  - PURPOSE: To develop a theory-guided culturally grounded narrative intervention to
      promote HPV vaccination behavior and examine the feasibility, acceptability, and
      preliminary effectiveness of the intervention among dyads of Cambodian American
      mothers and daughters. METHOD: The principles of community-based participatory
      research guided the development and evaluation and involved two phases: Phase 1:
      Development of storytelling narrative intervention videos which focused on a
      series of HPV vaccination-related messages and which integrated the narrative
      theory with the revised network episode model (rNEM); Phase 2: conducting the
      pilot RCT with 19 dyads of Khmer mothers and daughters aged from 14 to 17years to
      examine the feasibility and acceptability of the study. FINDINGS: Recruitment was
      completed in 7months with an overall retention of 84%. The acceptability of the
      intervention was high, as reflected by the number of positive comments on the
      narrative video. Preliminary data indicate that vaccine uptake at one-month
      follow-up was the same (2 vs. 2) between intervention and control groups.
      However, daughters in the narrative intervention group reported higher intention
      to receive HPV vaccination within one month compared to the control group (4 vs.
      1). CONCLUSION: All the procedures to inform a full RCT were examined, including
      identification of eligible participants, recruitment, randomization, intervention
      adherence, and short-term follow-up. The positive preliminary outcomes and
      feedback support the feasibility and potential effectiveness of the theory-guided
      narrative intervention.

PMID- 29579500
TI  - Nursing duties and accreditation standards and their impacts: The nursing
      perspective.
AB  - BACKGROUND: Medical advances and increasingly complex patients presenting to the
      Emergency Department (ED) make nursing challenging. Gaining new knowledge and
      skills is a perpetual requirement. New quality initiatives to improve patient
      safety and care are being constantly introduced and create significant work and
      time pressures for healthcare providers involved. STUDY QUESTION: Do ED nurses
      support the introduction of new quality standards, in addition to their current
      heavy workload? STUDY DESIGN: A cross-sectional survey. METHODS: All ED nurses in
      the Edmonton zone were invited to complete a survey on nursing beliefs regarding
      various accreditation standards and their impacts. The survey was developed
      iteratively, involving study investigators, the Health Authority Management Team,
      and Nursing Managers. Response options included a 7-point Likert scale of
      agreement. Median ratings and interquartile ranges were determined for each
      survey statement. RESULTS: A total of 433/1241 (34.9%) surveys were completed.
      Respondents were RNs (91.4%), female (88.9%), with 0-5years ED experience
      (43.7%). Overall, respondents 'agreed' or 'strongly agreed' with the statements,
      indicating favourable attitudes towards Accreditation Canada standards and other
      quality initiatives. They were neutral towards universal domestic violence
      screening, and the differentiation between a Best Possible Medication History and
      medication reconciliation. CONCLUSIONS: Despite their heavy workload, nurses
      strongly agreed on the importance of medication reconciliation, falls risk, and
      skin care, but felt that improved documentation forms could support efficiency.
      This nursing perspective is valuable in informing attempts to standardize and
      simplify documentation, including the design and implementation of a provincial
      clinical information system.

PMID- 29579501
TI  - Experiences of women and men living with urinary incontinence: A phenomenological
      study.
AB  - AIMS: To explore and understand, from a gender-based perspective, the quality-of
      life experiences of men and women who suffer from urinary incontinence.
      BACKGROUND: Urinary incontinence (UI) is a major health problem with significant
      social, psychological, occupational, sexual and economic effects leading to a
      substantial decrease in quality of life. Although this condition is increasingly
      frequent in men, research has tended to focus on women, adopting a quantitative
      approach. DESIGN: The data were examined using interpretive phenomenological
      analysis (IPA). METHODS: The data were collected through a semi-structured
      interview conducted between January and June 2016. An inductive discourse content
      analysis was performed in three stages: preparation, organization and report.
      Participants were recruited until data saturation was achieved. FINDINGS: A
      sample of 33 participants was recruited: 17 women and 16 men. Gender-specific
      features were found. Six categories emerged: (i) normalization of incontinence;
      (ii) verbalization of the problem; (iii) social isolation; (iv)experienced
      feelings and emotions; (v) impact on daily routine; (vi) self-care strategies to
      address the problem in the most suitable way. CONCLUSION: Urinary incontinence
      has a negative effect on the quality of life of men and women. However, there are
      gender differences as to how this phenomenon is experienced, particularly with
      regard to its psychological and social dimensions. A comprehensive, targeted
      assessment of the needs of these men and women is required on the part of
      professional nurses.

PMID- 29579502
TI  - Surgical weight loss as a life-changing transition: The impact of interpersonal
      relationships on post bariatric women.
AB  - : Surgical Weight Loss as A Life-changing Transition: The Impact of Interpersonal
      Relationships on Post-Bariatric Women BACKGROUND: Although women account for 80%
      of patients having bariatric surgery (BS), the complex psychosocial mechanisms
      that accompany this transformation process have not been well established.
      PURPOSE: The purpose of this study is to explore the lived experience of women
      transitioning in their interpersonal relationships post BS. METHODS: A semi
      structured interview with four questions was used. Six women, from six to 12
      months post BS, were interviewed. The interviews were recorded, transcribed and
      analyzed using thematic analysis. MAIN FINDINGS: By seeking support systems prior
      to undergoing BS, adequate social support was received during their recovery
      period. Attending bariatric support group meetings and using social media were
      significant to these women's satisfactory recovery. Relationship adjustments were
      sometimes needed, but overall these women established fulfilling social lives.
      Within the first year post bariatric surgery, women began to gain emotional
      strength and inspire others to lose weight as well. CONCLUSIONS: By inquiring
      about the psychosocial concerns of women who have undergone BS, healthcare
      providers can provide a more practical wellness plan.

PMID- 29579503
TI  - Effect of peripheral IV based blood collection on catheter dwell time, blood
      collection, and patient response.
AB  - AIM: To evaluate the effect of daily PIV-based phlebotomy using the PIVO device
      on PIVC dwell times and replacement rates, as well as the reliability of blood
      sample collection, and patient response to this method of blood collection.
      BACKGROUND: Blood draws which are also known as phlebotomy for laboratory
      analyses are one of the most common experiences for hospitalized patients. When
      performed by venipuncture, they are often associated with pain and anxiety for
      patients. Most hospitals avoid phlebotomy from peripheral IV catheters due to
      sample hemolysis, sample dilution by fluids in PIVC line or infused medications,
      PIVC dislodgement or infiltration, and increased rates of phlebitis. METHODS: A
      prospective, randomized- controlled study of 160 GI surgery patients was
      enrolled. Patients were randomized to either control evaluation of PIVC dwell or
      to receive daily PIVO blood collections in addition to evaluation of PIVC dwell.
      RESULTS: Daily PIVO blood collections did not negatively affect PIVC dwell or
      replacement rates. Overall 81% of blood collection attempts were successful and
      the likelihood of success was strongly associated with PIVC condition. Patients
      reported 0.7/10 pain for PIVO blood collection on a 0-10 pain scale and a 9.1/10
      preference for PIVO on a 0 (strongly prefer needle) to 10 (strongly prefer PIVO)
      preference scale. Results suggest that use of a PIV based blood collection was a
      reliable and valid approach and was superior to routine phlebotomy in self
      reported responses from patients.

PMID- 29579504
TI  - Mixed methods evaluation of a quality improvement and audit tool for nurse-to
      nurse bedside clinical handover in ward settings.
AB  - BACKGROUND: Nurse bedside handover quality is influenced by complex interactions
      related to the content, processes used and the work environment. Audit tools are
      seldom tested in 'real' settings. OBJECTIVE: Examine the reliability, validity
      and usability of a quality improvement tool for audit of nurse bedside handover.
      DESIGN: Naturalistic, descriptive, mixed-methods. SETTING: Six inpatient wards at
      a single large not-for-profit private health service in Victoria, Australia.
      PARTICIPANTS: Five nurse experts and 104 nurses involved in 199 change-of-shift
      bedside handovers. METHODS: A focus group with experts and pilot test were used
      to examine content and face validity, and usability of the handover audit tool.
      The tool was examined for inter-rater reliability and usability using observation
      audits of handovers across six wards. Data were collected in 2013-2014. RESULTS:
      Two independent observers for 72 audits demonstrated acceptable inter-observer
      agreement for 27 (77%) items. Reliability was weak for items examining the
      handover environment. Seventeen items were not observed reflecting gaps in
      practices. Across 199 observation audits, gaps in nurse bedside handover practice
      most often related to process and environment, rather than content items.
      Usability was impacted by high observer burden, familiarity and non-specific
      illustrative behaviours. CONCLUSION: The reliability and validity of most items
      to audit handover content was acceptable. Gaps in practices for process and
      environment items were identified. Context specific exemplars and reducing the
      items used at each handover audit can enhance usability. Further research is
      needed to develop context specific exemplars and undertake additional reliability
      testing using a wide range of handover settings. WHAT IS ALREADY KNOWN ABOUT THIS
      TOPIC: CONTRIBUTION OF THE PAPER.

PMID- 29579505
TI  - Exercises improve body composition, cardiovascular risk factors and bone mineral
      density for menopausal women: A systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Menopause has been considered as an aggravating factor for developing
      cardiovascular diseases and the metabolic syndromes for women. Exercise might be
      an effective intervention for reducing such threats. OBJECTIVE: The purpose of
      this study was to evaluate the exercise effects on body composition,
      cardiovascular risk factors, and bone mineral density of menopausal women.
      METHODS: Two reviewers did a complete search of five electronic database
      (Medline, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, and the
      Chinese Electronic Periodical Service) records up to January 31, 2014. Randomized
      controlled trials (RCTs) that compared female menopausal participants with
      exercises, and those without exercise or with placebo were included. Risk of bias
      was classified based on the Cochrane Collaboration tool, the meta-analysis was
      conducted using Comprehensive Meta-Analysis Version 2.2. The study selection,
      data extraction, and validation were performed independently by the 2 reviewers.
      RESULTS: A total of 17 RCTs with 792 participants were included for meta
      analysis. Among the eight RCTs (247 participants), a moderate effect size of
      exercise on body fat was found (SMD=-0.34, 95% CI: -0.60 to -0.08). In five RCTs
      (195 participants), a moderate effect size of exercise on waist circumference
      (SMD=-0.39, 95% CI: -0.68 to -0.09), in seven RCTs (162 participants), a moderate
      effect size on triglyceride level (SMD=-0.37, 95% CI: -0.62 to -0.11), and in
      five RCTs (311 participants), a moderate effect size on bone mineral density
      (SMD=0.38, 95% CI: 0.08-0.68). Subgroup analysis revealed a significant effect of
      aerobic exercise on body fat (SMD=-0.29, 95% CI: -0.53 to -0.06), and a short
      term exercise on body fat (SMD=-0.50, 95% CI: -0.89 to -0.11) and on
      triglycerides (SMD=-0.42, 95% CI: -0.79 to -0.04). The trials included in this
      meta-analysis were small and some had methodologic limitations. CONCLUSIONS: This
      study provides evidences to clinical practice for menopause women that exercise,
      compared with nonexercise or placebo exerted significant benefits on body fat,
      waist circumference, triglyceride level, and lumbar spine bone mineral density.
      Particularly, aerobic exercise did help menopausal women improve their body fat.
      A short-term exercise intervention had a benefit on not only body fat but also
      triglyceride level. However, well-designed, well-executed RCTs, and a detailed
      long-term clinical research should be needed in the future.

PMID- 29579506
TI  - A preliminary psychometric evaluation of the eight-item cognitive load scale.
AB  - AIM: The aim of this article is to report the psychometric properties of the
      eight-item cognitive load scale. BACKGROUND: According to cognitive load theory,
      the formatting and delivery of healthcare education influences the degree to
      which patients and/or family members can engage their working memory systems for
      learning. However, despite its relevance, cognitive load has not yet been
      evaluated among surrogate decision makers exposed to electronic decision support
      for healthcare decisions. To date, no psychometric analyses of instruments
      evaluating cognitive load have been reported within healthcare settings. METHODS:
      A convenience sample of 62 surrogate decision makers for critically ill patients
      were exposed to one of two healthcare decision support interventions were
      recruited from four intensive care units at a tertiary medical center in
      Northeast Ohio. Participants were administered a battery of psychosocial
      instruments and the eight-item cognitive load scale (CLS). RESULTS: The CLS
      demonstrated a bidimensional factor structure with acceptable discriminant
      validity and internal consistency reliability (Cronbach's alpha = 0.75 and 0.89).
      CONCLUSIONS: The CLS is a psychometrically sound instrument that may be used in
      the evaluation of decision support among surrogate decision makers of the
      critically ill. The authors recommend application of the cognitive load scale in
      the evaluation and development of healthcare education and interventions.

PMID- 29579507
TI  - Editorial Call for Papers for Special Topical Issues of Archives of Psychiatric
      Nursing.

PMID- 29579508
TI  - Effects of Mandala Art Therapy on Subjective Well-being, Resilience, and Hope in
      Psychiatric Inpatients.
AB  - PURPOSE: This study investigated the effects of Mandala art therapy on subjective
      well-being, resilience, and hope among psychiatric inpatients. METHODS: Recruited
      36 people who had been treated as inpatients in a psychiatric ward at a
      university hospital in Seoul, South Korea, and divided them evenly into
      experimental and control groups. The experimental group was required to attend a
      total of 8 sessions of Mandala art therapy, twice per week, between August 11 and
      October 30, 2015; measures of the three main variables were administered at pre
      test and post-test in both groups. RESULTS: Hope significantly increased in both
      groups, but the overall increase was greater in the experimental group (mean
      score of 9.5 and 15.3 at pre- and post-test, respectively) than in the control
      group (10.9 and 11.9). CONCLUSION: These results suggest that Mandala art therapy
      can have a positive effect on the hope of psychiatric inpatients. However,
      further research concerning its effects on subjective well-being and resilience,
      as well as other psychological constructs, is warranted to better understand the
      effects of Mandala art therapy on psychiatric inpatients.

PMID- 29579509
TI  - A Comparison of Aggression and Self-injury Among Type 1 Diabetic and Healthy
      Adolescents: A Sample From Turkey.
AB  - BACKGROUND: Adolescents tend to have risky behaviors like aggression and self
      injury due to the age period characteristics. The risk of aggression and self
      injury may increase in adolescents with the addition of chronic diseases.
      OBJECTIVES: This study was conducted descriptively to determine and compare the
      aggression and self-injury in those with type 1 diabetes mellitus (T1DM) and
      healthy counterparts. METHODS: The study sample consisted of 60 adolescents with
      T1DM followed up in the child endocrinology polyclinic of a university hospital
      and 319 healthy counterparts, 15-18 aged, at 9th-12th grade at high school. In
      the study, the permission of the institution, Ethical Committee, the parent and
      adolescent consent, the data were collected using a questionnaire form,
      Aggression Questionnaire (AQ) and Inventory of Statements About Self-injury
      (ISAS). The descriptive statistics, Shapiro-Wilk, Mann-Whitney U, Student t, Chi
      square, Spearman correlation tests were used for analyzing data. RESULTS: The
      mean scores of AQ all subscales and the total scale of healthy adolescents were
      higher than adolescents with T1DM (p<0.05). Mean ISAS scores of adolescents with
      T1DM were higher than the healthy ones (p>0.05). The mean scores of autonomic
      function, social function and ISAS were positively moderately correlated with the
      mean scores of total aggression in both healthy and diabetic adolescents
      (p<0.05). CONCLUSIONS: Considering the age period characteristics, training about
      anger-stress management and effective communication skill to adolescents and
      their parents may be recommended by health professionals.

PMID- 29579510
TI  - Effectiveness of Needs-oriented Hospital Discharge Planning for Caregivers of
      Patients With Schizophrenia.
AB  - Hospital discharge planning for clients with schizophrenia reduces client
      rehospitalization rates and improves their medication adherence. The
      effectiveness of caregiver participation in hospital discharge planning has
      seldom been explored. The purpose of this study was to examine the effectiveness
      of caregiver participation in hospital discharge planning for clients with
      schizophrenia in reducing caregiver burden and improving health status. A quasi
      experimental research design was adopted. The research location was in a
      psychiatric hospital in Northern Taiwan. The target population was caregivers of
      inpatients with schizophrenia. Nurses served as care coordinators and provided
      six-step hospital discharge planning services to caregivers. Structured
      questionnaires were employed to measure caregiver burden and health status.
      Intervention effect was tested using analysis of covariance in which outcome
      measure at pretest and selected demographic variables were treated as covariates.
      A total of 114 caregivers completed pretest and posttest evaluations, with 57
      people in each group. A significant difference was found between the experimental
      and the control group regarding the caregiver burden and health status (P<0.001)
      The caregiver burden and health status of the experimental group improved more
      significantly compared with the control group. The caregiver-involved discharge
      planning process developed in this study effectively reduced the burden placed on
      caregivers and improved their health status. Mental health nurses can serve as
      the main care coordinators for assessment, planning, referral and provision of
      the required services. Caregiver-involved hospital discharge planning should
      become part of the routine care process.

PMID- 29579511
TI  - Post-traumatic Stress Disorder Among Health Care Providers Two Years Following
      the Israeli Attacks Against Gaza Strip in August 2014: Another Call for Policy
      Intervention.

PMID- 29579512
TI  - Eating Behaviors and Related Factors in Psychiatric Patients.
AB  - The aim of this study was to determine the risk of eating disorders and
      associated risk factors in individuals with psychiatric disorders. Patients who
      were hospitalized in a psychiatry clinic of the university hospital between the
      dates of February 2014 and July 2014 constitute sample for the study. The study
      sample consisted of a total of 216 patients. Data were collected using a
      questionnaire form and the Eating Attitude Test. The mean age of the patients was
      37+/-0.5, and 56.9% of the patients were female. Problems in eating behavior were
      observed in 11.6% of the patients, and a statistically significant relationship
      was found between the risk of eating disorders and diagnosis, gender, exercise
      and self-perception of weight. The risk of eating disorders was more frequently
      observed in patients diagnosed with depression, in female patients with a self
      perceived weight problem and do not exercise.

PMID- 29579513
TI  - A Comparison of Eating Attitudes Between Vegans/Vegetarians and
      Nonvegans/Nonvegetarians in Terms of Orthorexia Nervosa.
AB  - This descriptive study was performed to compare signs of orthorexia nervosa and
      eating habits and attitudes of vegans/vegetarians and nonvegans/nonvegetarians.
      The study sample included 62 people, of whom 31 were vegan/vegetarian and 31 were
      nonvegan/nonvegetarian. Data were gathered with a personal characteristics form,
      Orthorexia Nervosa Evaluation Scale-11, Eating Attitudes Test-40 and Maudsley
      Obsessive Compulsive Inventory. There were not any significant differences
      between scores for Orthorexia Nervosa Evaluation Scale-11, Eating Attitudes Test
      40 and Maudsley Obsessive Compulsive Inventory (p>0,05). As scores for Orthorexia
      Nervosa Evaluation Scale-11 decreased, predisposition to orthorexia nervosa
      increased. Therefore, although correlation coefficients were negative, they were
      considered positive. There was a significant, negative relation between Eating
      Habits Test-40 scores and Orthorexia Nervosa Evaluation Scale-11 scores (r=
      0.290, p=0.002) and between Maudsley Obsessive Compulsive Inventory scores and
      Orthorexia Nervosa Evaluation Scale-11 scores (r=-0.319, p=0.012). As poor eating
      habits and obsessive symptoms increased, so did orthorectic symptoms. In light of
      obtained results, it seems that people become vegan/vegetarian mainly for ethical
      reasons and that veganism/vegetarianism is not associated with obsession of
      healthy eating.

PMID- 29579514
TI  - The Mental Health Team: Evaluation From a Professional Viewpoint. A Qualitative
      Study.
AB  - BACKGROUND: Health care institutions include workers who must operate in
      accordance with the requirements of the position, even though there are
      psychosocial influences that can affect the stability of the worker. AIMS: To
      analyze the organizational culture of the team of professionals who work in the
      mental health network. METHOD: A qualitative methodology was used to assess a
      sample of 55 mental health professionals who have been practicing for at least
      5years. RESULTS: "Team" was the overall topic. The subtopics within "Team" were:
      getting along in the unit, getting along with the patient, personal resources for
      dealing with patients, adaptive resources of team members and, resources that the
      team uses in their group activities. CONCLUSION: It was observed that the team
      does not work with a common objective and needs an accepted leader to manage the
      group. The definition and acceptance of roles can result in conflict. By
      increasing the skill level of each worker, the multidisciplinary team would be
      more collaborative.

PMID- 29579515
TI  - Exploration of Aggression/Violence Among Adult Patients Admitted for Short-term,
      Acute-care Mental Health Services.
AB  - BACKGROUND/PURPOSE: The purpose of the study was to explore and describe: (a) the
      prevalence of incidents of aggression and violence among patients, including
      frequency, kinds and severity of incidents of among patients; target of the
      aggression; (b) situational factors including time of location and time of event;
      and (c) staff interventions. We describe the relationships among variables to
      answer the following research questions: (1) What factors are associated with
      incidents of aggression and violence, and (2) are factors modifiable? METHODS:
      The exploratory descriptive study used data collected by retrospective chart
      review over a three-year period; the dates of January 1, 2011 to December 31,
      2013. A medical record was included if it met the following criteria: 1) person
      ages 18-75years; 2) admitted to the psychiatric mental care unit (PMCU) during
      the designated time frame; 3) the length of stay was up to 7days; and 4) during
      this time the person made a verbal threat of violence or exhibited violent
      behavior towards property, self, another patient, or a member of the hospital
      staff. We examined data for a relationship among score on risk assessment items,
      sociodemographic factors, and outcome variables. We employed a variety of
      statistical analytic approaches to describe our data and uncover relationships
      among variables. RESULTS: There were 132 incidents of aggression/violence between
      January 1, 2011 and December 31, 2013Of the 93 patients, 68% (n=63) were male and
      32% (n=30) were female. Their ages ranged from 20 to 57years with a mean age of
      37 for females and 39 for males. Significant associations were found between type
      of intervention and patients' admitting diagnoses: Chi2 (5, N=97)=11.603,
      p=0.004. Significant associations were also found with regard to drug history,
      Chi2(1, n=96)=4.673, p=0.03 and history of violence, Chi2(1, N=91)=7.618,
      p=0.006. Key variables were target (the staff) and location (the hallway).
      Multiple factor analysis yielded inconclusive results, as numerous factors were
      identified and variable loadings were weak possibly due to the small sample size
      and high number of relevant variables. CONCLUSION: Findings from this study can
      be used to improve high quality care for hospitalized patients with acute mental
      health problems. All incidents of aggression/violence cannot realistically be
      prevented. Staff must stay vigilant for self-safety. The hallway may be modified
      to reduce visual and auditory stimuli.

PMID- 29579516
TI  - Impact of Menopause on Quality of Life in Community-based Women in China: 1 Year
      Follow-up.
AB  - Quality of life (QOL) throughout menopause has become an outcome variable
      requiring measurement in clinical care. Staff nurses can provide earlier nursing
      during the menopausal transition (MT) stage. The purpose of this study was to
      describe the changes of QOL in different stages of the MT according to The Stages
      of Reproductive Aging Workshop (STRAW) in Chinese women in community settings.
      Prospective longitudinal study design was used to analyze QOL of 327 community
      women age 30-65years old. They were followed up at 1-year. An instrument
      including the Chinese version of the Menopause-Specific Quality of Life
      Questionnaire was used to obtain data. A gradual decline in QOL was seen from
      premenopausal to menopausal transition (MT) and in postmenopausal women.
      Significant differences were observed in vasomotor, physical and sexual scores at
      baseline and follow-up (P<0.05). Significant differences in vasomotor scores were
      observed between baseline and follow-up for women in the premenopausal and Late
      MT stages (P<0.05). There were significant differences in psychosocial and
      physical scores between baseline and follow-up in the Late MT stage (P<0.05).
      Menopause might have a negative impact on QOL independent of age in community
      based women in China. There seemed to be a potential model of the relationship of
      menopause status to change in QOL, but this needs supporting evidence from longer
      longitudinal studies.

PMID- 29579517
TI  - The Relationship Between the Burden of Caregiving, Submissive Behaviors and
      Depressive Symptoms in Primary Caregivers of Patients With Schizophrenia.

PMID- 29579518
TI  - Correlations between stress, anxiety and depression and sociodemographic and
      clinical characteristics among outpatients with heart failure.
AB  - : Aim To describe and investigate correlations among anxiety, stress and
      depression and identify their relationship with sociodemographic and clinical
      characteristics of patients with heart failure. METHODS: This is an analytical
      cross-sectional study. Sociodemographic and clinical characteristics were
      collected, along with levels of anxiety, stress and depression from 309
      outpatients. RESULTS: The mean levels of stress, anxiety and depression were
      correlated but low. Time since diagnosis, the disease's functional class, family
      income, and smoking influenced stress. Functional class and Chagas disease
      influenced anxiety and depression. Being unemployed and smoking influenced
      anxiety, while being a homeowner influenced depression. CONCLUSION: These
      findings should be considered when planning nursing interventions.

PMID- 29579519
TI  - Prevalence of Workplace Violence Against Chinese Nurses and Its Association with
      Mental Health: A Cross-sectional Survey.
AB  - OBJECTIVES: The aim of this study to investigate the prevalence of workplace
      violence (WPV) in nurses in hospitals in China, and its influence on nurses'
      mental health. METHODS: A cross-sectional, anonymous survey was conducted with
      886 nurses (effective response rate: 87.46%) from Heilongjiang Province of China.
      RESULTS: Findings revealed that 595 of the 886 participating nurses (67.2%) were
      exposed to different levels of WPV. Further, WPV was correlated positively with
      nurses' anxiety (r=0.256, P<0.01) and depression (r=0.131, P<0.01) levels. In
      addition, this survey demonstrated that service years (r=0.263, P<0.01) played a
      moderating role in the relationship between WPV and anxiety, and gender (r=0.135,
      P<0.01) played a moderating role in the association between WPV and depression.
      CONCLUSIONS: WPV is an extensive problem in the work setting of nurses and it
      poses a major threat to Chinese nurses. Chinese nurses encounter hospital
      workplace violence frequently, and WPV has a considerably negative impact on the
      mental health and well-being of the nurses. It is critical to establish a more
      secure working environment for Chinese nursing staff to minimize the health
      threats caused by the negative outcomes associated with WPV, such as symptoms
      caused by anxiety and depression. This study also confirmed that new nurses and
      female nurses were more likely to be affected by WPV. Thus, addressing WPV should
      be one of the top concerns for both the government and the society.

PMID- 29579520
TI  - Depression in Community-Dwelling Elderly Patients With Heart Failure.
AB  - The present cross-sectional study discussed the relationship between comorbid
      depression, demographic characteristics, clinical characteristics, and dietary
      self-efficacy among Taiwanese community-dwelling elderly patients with heart
      failure (HF). Specifically, the study examined 175 community-dwelling elderly
      patients with HF between July 2013 and June 2014. In total, 47.13% of the
      patients exhibited symptoms of depression. Those without a spouse, who were
      currently employed, who had an ejection fraction <30%, who had been readmitted to
      the hospital 2 or more times, and who had a high level of HF symptom distress
      were significantly more likely to be depressed. Therefore, it is crucial that
      care programs designed for these patients include the self-management of HF
      symptoms, psychological consultations, cognitive behavioral therapy, and physical
      exercise.

PMID- 29579521
TI  - Social Support as a Mediator of Physical Disability and Depressive Symptoms in
      Chinese Elderly.
AB  - The relationship between physical disability and depressive symptoms has been
      associated with social support. Different aspects of social support may play
      distinct roles in health-related quality of life. The aim of this study was to
      examine the mediation of social support in the relationship between physical
      disability and depressive symptoms among old people in Mainland China. Subjective
      support and utilization of support mediated the relationship between ADL and
      depressive symptoms, with the indirect effect of subjective support and
      utilization of support at 0.038 and 0.030 respectively (the total effect was
      0.180). Subjective support was negatively associated with depressive symptoms in
      independent elderly people, utilization of support was negatively associated with
      depressive symptoms in partially dependent elderly people, and utilization of
      support had a greater association with geriatric depressive symptoms than
      subjective support in severely dependent elderly people. Social support mechanism
      and positive psychological intervention should be established and introduced in
      accordance with the physical disability of the elderly people, to protect them
      from depressive symptoms.

PMID- 29579522
TI  - The Relationship of Maternal-Fetal Attachment and Postpartum Depression: A
      Longitudinal Study.
AB  - AIM: To determine the relationship between maternal-fetal attachment and
      postpartum depression. METHODS: This longitudinal study was done on 242
      primiparous women in 2016. The data collection tools used included a socio
      demographic characteristics questionnaire and Cranley's Maternal-Fetal Attachment
      Scale - which was completed at 32-37weeks of pregnancy - and obstetrics
      information questionnaire and the Edinburgh Postnatal Depression Scale -which was
      completed at 6-8weeks after birth. A multivariate linear regression was used to
      estimate the extent to which maternal-fetal attachment affected postpartum
      depression. RESULTS: The mean Maternal-Fetal Attachment score was 90.0 (SD: 10.3)
      from the attainable score of 23 to 115. The mean depression score was 8.0 (SD:
      3.8) from the attainable score of 0 to 30. Pearson's correlation test showed a
      significant inverse relationship between maternal-fetal attachment and postpartum
      depression (r=-0.196, p<0.001). The multivariate linear regression model showed
      that postpartum depression correlated significantly with the mother's age and two
      dimensions of attachment including differentiation of self from fetus and
      attributing characteristics to the fetus. CONCLUSION: According to the findings,
      maternal-fetal attachment is one of the factors contributing to postpartum
      depression. Greater emphasis should be placed on the preparation of pregnant
      women for accepting their maternal role, so that the maternal-neonatal
      relationship can be enhanced and postpartum depression thus reduced.

PMID- 29579523
TI  - Impact of the I2AO2 interdisciplinary program led by nursing on psychological
      comorbidity and quality of life: Randomized controlled clinical trial.
AB  - OBJECTIVE: Obesity is an entity of highly prevalent multifactorial origin with
      associated metabolic and psychological comorbidity, causing a negative impact on
      the quality of life of those who suffer from it. The objective is to evaluate the
      impact of an interdisciplinary program for nurse-led obesity on quality of life
      related to health and anxiety. METHODS: Randomized controlled clinical trial with
      a sample of 74 subjects diagnosed with obesity (EG: n=37; CG: n=37). The
      intervention consisted of a 12-month interdisciplinary program (with pre-test,
      12month and 24month follow-up) coordinated by nurses. RESULTS: The anxiety
      analysis shows that there is no effect of the intervention on S-STAI (F2;
      144=0.246; p=0.782), which has increased in both groups. However, there is an
      effect on T-STAI (F2; 144=8872; p<0.001), which only increases in the control
      group. The interdisciplinary program has significantly improved health-related
      quality of life (SF-36), both in physical health parameters as well as in mental
      health. CONCLUSION: The interdisciplinary program led by nursing professionals
      has improved the quality of life related to health and has prevented the increase
      of anxiety-trait in participants, maintaining the long-term effects.

PMID- 29579524
TI  - Effects of Relaxation Therapy on Anxiety Disorders: A Systematic Review and Meta
      analysis.
AB  - AIM: To explore the effect of relaxation therapy applied to people with anxiety
      disorders. METHODS: Systematic review with meta-analysis. RESULTS: Sixteen
      Randomized Control Trials (RCTs) were included for meta-analysis to determine the
      effect of relaxation therapy. The overall effect of relaxation therapy on symptom
      of anxiety was significant with Hedges' g=0.62 (95% CI: 0.42-0.81), which
      indicates a medium-high effect; heterogeneity was statistically significant with
      I2=48.84. Subgroup analysis exploring the possible causes of heterogeneity found
      that types of comparison of TAU and CBT was significant (Q=4.20, p=0.04). The
      effect of relaxation therapy on symptoms of depression, phobia, and worry was
      significant; Hedges' g=0.44 (95% CI: 0.30-0.59), 0.40 (95% CI: 0.06-0.75), 0.54
      (95% CI: 0.28-0.79), respectively. CONCLUSION: The results of this study provide
      evidence for the effectiveness of relaxation therapy for people with anxiety
      disorders. Therefore, relaxation therapy can be selected as a useful intervention
      for reducing negative emotions in people with anxiety disorders.

PMID- 29579525
TI  - Do Males and Females Conceptualise Work and Social Impairment Differently
      Following Treatment for Different Mental Health Problems?
AB  - The Work and Social Adjustment Scale (WSAS) is used by psychiatric nurses for
      screening and evaluating patients' treatment outcomes for a variety of mental
      health problems. This study investigated longitudinal and gender measurement
      invariance of WSAS using structural equation modeling within a help-seeking
      problem gambling sample (n=445), and an intervention program for depression and
      anxiety sample (n=444). The concept of functional impairment was defined by all
      WSAS items in males and females at pre- and post-treatment assessments. These
      findings confirm that the WSAS is a robust and efficacious instrument for
      evaluating treatment outcomes in two differing populations.

PMID- 29579526
TI  - Safe and Collaborative Communication Skills: A Step towards Mental Health Nurses
      Implementing Trauma Informed Care.
AB  - Trauma Informed Care (TIC) acknowledges the presence and effects of trauma in the
      lives of many mental health service users and the responsibility of services to
      provide physical and emotional safety. One challenge of TIC is a lack of clarity
      about translating the philosophy into practice. This paper describes the delivery
      and evaluation of a trauma informed communication workshop for mental health
      nurses that aimed to increase their knowledge of the potential impacts of trauma
      on consumers, and translate TIC concepts into their communication approaches
      within the therapeutic relationship.

PMID- 29579527
TI  - Knowledge and Attitude of Family Member of Mentally Ill Patient Regarding
      Restraint, 2016.
AB  - BACKGROUND: People who have observed or are aware that a consumer has been
      restrained may experience distress, confusion, concern, anger or fear and
      perceive as punishment. However, studies that examine the perspective of
      patient's family are limited. This study has explored the knowledge and attitude
      of family member of mentally ill patient. METHOD: A descriptive cross-sectional
      study was carried out among family member of mentally ill patient at Punarjeevan
      Hospital, Balkumari, Lalitpur to assess the knowledge and attitude of family
      member of mentally ill patient regarding restraint. Interview schedule was used
      to collect data related to knowledge and attitude regarding restraint along with
      demographic features. RESULT: The average score of knowledge regarding physical
      restraint was 30.66 (72.99%) and average attitude score was 4.17 (83.31%). In the
      study 40% relationship was found between knowledge and attitude. Regarding the
      association between knowledge and selected socio-demographic variables, knowledge
      was found to be associated with age, educational level and relation with patient
      of respondents. In terms of association between attitude and selected socio
      demographic variables, attitude was found to be associated with relation with
      patient of respondents. CONCLUSION: This study concludes that family member has
      relevant knowledge regarding physical restraint but the knowledge regarding risk
      and consequences of physical restraint was lacking. In terms of attitudes about
      physical restraint over all attitude was found to be positive among family
      members but attitude regarding feeling of patient towards physical restraint was
      contrast.

PMID- 29579528
TI  - Decision-making Capacity for Treatment of Psychotic Patients on Long Acting
      Injectable Antipsychotic Treatment.
AB  - OBJECTIVE: Providing informed, consent requires patients' Decision-Making
      Capacity for treatment. We evaluated the Decision Making Capacity of outpatients
      diagnosed with schizophrenia and schizoaffective disorder on treatment with Long
      Acting Injectable Antipsychotic medication. METHOD: This is a retrospective,
      cross-sectional, correlational study conducted at two Depot Clinics in Athens,
      Greece. Participants included 65 outpatients diagnosed with schizophrenia and
      schizoaffective disorder on treatment with Long Acting Injectable Antipsychotics.
      RESULTS: Over half of the participants showed poor understanding of the
      information given regarding their disease and treatment (Understanding subscale),
      however >70% seemed to comprehend the relevance of this information to their
      medical condition (Appreciation subscale). Moreover, half of the participants
      reported adequate reasoning ability (Reasoning subscale), whilst patients who
      gained >7% of their body weight scored statistically significantly higher in the
      subscales of Understanding and Appreciation. CONCLUSION: Our results suggest that
      there is a proportion of patients with significantly diminished Decision Making
      Capacity, hence a full assessment is recommended in order to track them down.
      Further research is needed to better interpret the association between
      antipsychotic induced weight gain and Decision Making Capacity in patients
      suffering from schizophrenia or schizoaffective disorder.

PMID- 29579529
TI  - Pathological Gambling among Italian Nursing Students.
AB  - PURPOSE: To investigate the role of psychiatric dimensions, behavioral or
      substance addictions and demographical variables as determinants of pathological
      gambling among nursing students. DESIGN: Multicenter cross-sectional study.
      METHODS: From June to October 2015 a survey was carried out among Italian Nursing
      students. Data were collected using a six-section tool. FINDINGS: Nursing
      students who completed the survey numbered 1083, 902 (83.3%) had some problems
      with gambling and 29 (2.7%) showed pathological gambling. Percentage of
      pathological gambling was significantly associate with illicit drug/alcohol use
      (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non
      pathological gambling (20%) and those with some problem (24.2%). Significant main
      effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT
      scores were associated with higher SOGS scores. CONCLUSIONS: Italian nursing
      students have some problems with gambling and pathological gambling problem, and
      males are those who have more problems. Results might be useful for faculties of
      health professionals to identify students at risk in an early stage, to direct
      prevention tailored interventions. CLINICAL RELEVANCE: Nursing faculties should
      be aware of the prevalence of Gambling among students. Prevention interventions
      should be planned to minimize the risk of gambling behavior in the future nurses'
      health care workers.

PMID- 29579530
TI  - Relationship of Student Nurses' Substance Misuse to Perceptions of Peer Substance
      Use and Harmfulness.

PMID- 29579531
TI  - Self-stigma, mentally ill persons and health services: An integrative review of
      literature.
AB  - Integrative review about self-stigma among people with mental illness and its
      relationship with health services. A total of 149 articles were found in four
      databases. After screening, 9 articles were selected for complete reading and
      data extraction. The studies identified that higher levels of self-stigma result
      in lower levels of adherence to treatment and that lower levels of self-stigma
      result in greater adherence to treatment. Active participation and engagement in
      the aspects of care facilitate the empowerment of people with mental illness for
      better adherence to treatment, reduction of self-stigma and increase of recovery
      possibilities.

PMID- 29579532
TI  - Corrigendum to "Personal and Perceived Depression Stigma among Arab Adolescents:
      Associations with Depression Severity and Personal Characteristics" [Archives of
      Psychiatric Nursing 31/5 (2017) 499-506].

PMID- 29579533
TI  - Chained nuclei and python pattern in skeletal muscle cells as histological
      markers for electrical injury.
AB  - Electrical injury is damage caused by an electrical current passing through the
      body. We have previously reported that irregular stripes crossing skeletal muscle
      fibers (python pattern) and multiple small nuclei arranged in the longitudinal
      direction of the muscle fibers (chained nuclear change) are uniquely observed by
      histopathological analysis in the skeletal muscle tissues of patients with
      electrical injury. However, it remains unclear whether these phenomena are caused
      by the electrical current itself or by the joule heat generated by the electric
      current passing through the body. To clarify the causes underlying these changes,
      we applied electric and heat injury to the exteriorized rat soleus muscle in
      situ. Although both the python pattern and chained nuclear change were induced by
      electric injury, only the python pattern was induced by heat injury. Furthermore,
      a chained nuclear change was induced in the soleus muscle cells by electric
      current flow in physiological saline at 40  degrees C ex vivo, but a python
      pattern was not observed. When the skeletal muscle was exposed to electrical
      injury in cardiac-arrested rats, a python pattern was induced within 5 h after
      cardiac arrest, but no chained nuclear change was observed. Therefore, a chained
      nuclear change is induced by an electrical current alone in tissues in vital
      condition, whereas a python pattern is caused by joule heat, which may occur
      shortly after death. The degree and distribution of these skeletal muscle changes
      may be useful histological markers for analyzing cases of electrical injury in
      forensic medicine.

PMID- 29579535
TI  - Electron paramagnetic resonance of a 10B-containing heterocyclic radical.
AB  - Electron paramagnetic resonance measurements for a 10B-containing heterocyclic
      phenanthrenedione radical, (C6F5)2B(O2C14H8), were made at X-band in 9:1
      toluene:dichloromethane from 10 to 293 K and in toluene from 180 to 293 K. In
      well-deoxygenated 0.1 mM toluene solution at room temperature hyperfine couplings
      to 10B, four pairs of protons and five pairs of fluorines contribute to a
      continuous wave spectrum with many resolved lines. Hyperfine couplings were
      adjusted to provide the best fit for spectra of the radical enriched in 10B and
      the analogous radical synthesized with 10,11B in natural abundance, resulting in
      small refinements of the hyperfine coupling constants previously reported for the
      natural abundance sample. Electron spin relaxation rates at temperatures between
      15 and 293 K were similar for samples containing 10B and natural isotope
      abundance. Analysis of electron spin echo envelope modulation and hyperfine
      correlation spectroscopy data at 80 K found Axx = -7.5 +/- 0.3, Ayy = -8.5 +/-
      0.3, and Azz = -10.8 +/- 0.3 MHz for 11B, which indicates small spin density on
      the boron. The spin echo and hyperfine spectroscopy data for the 10B -containing
      radical are consistent with the factor of 2.99 smaller hyperfine values for 10B
      than for 11B.

PMID- 29579534
TI  - Polymerase bypass of N7-guanine monoadducts of cisplatin, diepoxybutane, and
      epichlorohydrin.
AB  - DNA oligonucleotides containing site-specific N7-guanine monoadducts of
      cisplatin, diepoxybutane, and epichlorohydrin were used as templates for DNA
      synthesis by two bacterial DNA polymerases and human polymerase beta. These
      polymerases were able to bypass the lesions effectively, although the efficiency
      was decreased, with inhibition increasing with the size of the lesion. Fidelity
      of incorporation was essentially unaltered, suggesting that N7-guanine
      monoadducts do not significantly contribute to the mutational spectra of these
      agents.

PMID- 29579536
TI  - Novel forecasting approaches using combination of machine learning and
      statistical models for flood susceptibility mapping.
AB  - In this research, eight individual machine learning and statistical models are
      implemented and compared, and based on their results, seven ensemble models for
      flood susceptibility assessment are introduced. The individual models included
      artificial neural networks, classification and regression trees, flexible
      discriminant analysis, generalized linear model, generalized additive model,
      boosted regression trees, multivariate adaptive regression splines, and maximum
      entropy, and the ensemble models were Ensemble Model committee averaging (EMca),
      Ensemble Model confidence interval Inferior (EMciInf), Ensemble Model confidence
      interval Superior (EMciSup), Ensemble Model to estimate the coefficient of
      variation (EMcv), Ensemble Model to estimate the mean (EMmean), Ensemble Model to
      estimate the median (EMmedian), and Ensemble Model based on weighted mean
      (EMwmean). The data set covered 201 flood events in the Haraz watershed
      (Mazandaran province in Iran) and 10,000 randomly selected non-occurrence points.
      Among the individual models, the Area Under the Receiver Operating Characteristic
      (AUROC), which showed the highest value, belonged to boosted regression trees
      (0.975) and the lowest value was recorded for generalized linear model (0.642).
      On the other hand, the proposed EMmedian resulted in the highest accuracy (0.976)
      among all models. In spite of the outstanding performance of some models,
      nevertheless, variability among the prediction of individual models was
      considerable. Therefore, to reduce uncertainty, creating more generalizable, more
      stable, and less sensitive models, ensemble forecasting approaches and in
      particular the EMmedian is recommended for flood susceptibility assessment.

PMID- 29579537
TI  - Use of high metal-containing biogas digestates in cereal production - Mobility of
      chromium and aluminium.
AB  - Biogas digestate use as organic fertilizer has been widely promoted in recent
      years as a part of the global agenda on recycling waste and new sustainable
      energy production. Although many studies have confirmed positive effects of
      digestates on soil fertility, there is still lack of information on the potential
      adverse effects of digestates on natural soil heavy metal content, metal leaching
      and leaching of other pollutants. We have investigated the release of aluminium
      (Al) and chromium (Cr) from different soils treated with commercial digestates
      high in mentioned potentially problematic metals in a field experiment, while a
      greenhouse and a laboratory column experiment were used to address mobility of
      these metals in two other scenarios. Results obtained from the field experiment
      showed an increase in total concentrations for both investigated metals on plots
      treated with digestates as well as a significant increase of water-soluble Al
      concentrations. Factors that were found to be mostly affecting the metal mobility
      were dissolved organic carbon (DOC), pH and type of soil. Metal binding and free
      metal concentrations were modelled using the WHAM 7.0 software. Results indicated
      that the use of digestates with high metal content are comparable to use of
      animal manure with respect to metal leaching. Data obtained through chemical
      modelling for the samples from the field experiment suggested that an
      environmental risk from higher metal mobility has to be considered for Al. In the
      greenhouse experiment, measured concentrations of leached Cr at the end of the
      growing season were low for all treatments, while the concentration of leached Al
      from digestates was higher. The high irrigation column leaching experiment showed
      an increased leaching rate of Cr with addition of digestates.

PMID- 29579538
TI  - Relationship between geosorbent properties and field-based partition coefficients
      for pesticides in surface water and sediments of selected agrarian catchments:
      Implications for risk assessment.
AB  - Studies on pesticide behavior, adsorption-likelihood, and bioavailability vis-a
      vis geosorbent properties and seasons, are critical for understanding pesticide
      fate and risks in pesticide-prone environments. We examined the relationship
      between geosorbent profiles of sediments (percentage sand, silt, clay, organic
      carbon content) across seasons and occurrence of pesticide residues in surface
      water and sediment of agricultural catchments at Owan, Ogbesse and Illushi
      communities of Edo State, Nigeria. Pesticide concentrations were measured monthly
      in samples of surface water and sediments across the selected sites for 18
      months. Pesticide behavior and sorption-likelihoods were examined using partition
      coefficients Kd (sediment-water coefficient), Koc (sediment-water coefficient
      normalized for organic carbon) and Log Kow (octane-water coefficient); the
      relationship between Kd and Koc was also examined. Results of the principal
      component analysis (PCA) indicated that pesticide levels in sediment and surface
      water were positively associated with the rainy season, total organic content
      (TOC), percentage silt and clay in sediment. Field-derived pesticide partition
      coefficients (Kd < 100 and log Koc < 3) indicated that pesticide species were
      largely mobile and less likely to be retained in sediments by adsorption. As
      such, pesticides irrespective of solubility would end up in surface water,
      increasing risks for pelagic biota and humans sourcing river water for domestic
      use. Values of Log Kow indicate that organochlorines including DDT, dieldrin,
      endrin and heptachlor epoxide portend significant bioaccumulation risks to humans
      and biota across sites. The relationship between Kd and Koc for each site fitted
      into a quadratic model; it depicted a biphasic behavior of pesticide adsorption
      and desorption to sediments revealing that concentration of organic carbon across
      study sites was a limiting factor determining the extent of pesticide adsorption.
      This study demonstrates that understanding pesticide mobility using field-based
      partition coefficients could give a clearer picture of pesticide risks to biota
      and human populations.

PMID- 29579539
TI  - New directions on lung clearance index variability and feasibility.

PMID- 29579540
TI  - Pancreatitis from intra-gastric balloon insertion: Case report and literature
      review.
AB  - INTRODUCTION: Intra-Gastric Balloon (IGB) is increasingly used as a non-operative
      management strategy in bariatric patients. However, as IGB use has become more
      prevalent, new potentially life-threatening adverse effects have emerged. We
      report a case of IGB-related acute pancreatitis from a tertiary referral
      hospital. A literature review of electronic databases was conducted to identify
      other cases PRESENTATION OF CASE: A 20-year-old female presented to the emergency
      department with acute onset of epigastric pain on day-1 post-insertion of an IGB
      (Orbera(r)). The diagnosis of acute pancreatitis was made on the basis of the
      clinical picture, with radiological and serological confirmation. Complete
      resolution of symptoms promptly followed endoscopic removal of the balloon.
      DISCUSSION: We examine all prior reported cases of IGB associated pancreatitis in
      the literature, as well as the impact of the particular balloon subtypes. Mass
      effect of the device on the pancreas or dislodgement of the rigid catheter into
      the second part of the duodenum appear to be the underlying cause in all cases.
      While there were no deaths reported, major sequelae have been noted, including
      presence of mucosal ischemia and failure to retrieve the balloon endoscopically,
      necessitating laparotomy. CONCLUSION: Although the incidence of IGB-induced
      pancreatitis is still rare, this complication which must be highlighted as a
      potentially serious adverse outcome.

PMID- 29579541
TI  - SET promotes H2Ak9 acetylation by suppressing HDAC1 in trichloroethylene-induced
      hepatic cytotoxicity.
AB  - Trichloroethylene (TCE) was widely used as an industrial solvent which could
      cause severe liver damage. The histone chaperone SET have been identified as an
      important mediator of TCE-induced hepatic cytotoxicity in our previous study;
      however, the underlying regulatory mechanisms remain poorly understood. In this
      study, we found a total of 136 histone acetylation sites involved in TCE-induced
      hepatic cytotoxicity with the technique of Triton-acid-urea polyacrylamide gel
      electrophoresis (TAU-PAGE) coupled with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Importantly, 17 histone acetylation sites were revealed
      to be mediated by SET in TCE-induced cytotoxicity. The acetylation of histone
      H2AK9 (H2AK9ac) was further validated by Western-blot analysis. The data showed
      that TCE treatment increased the acetylation of H2AK9 in hepatic L-02 cell and
      decreased the one in SET-knockdown L-02 cells. Besides, levels of the histone
      deacetylases (HDACs, including HDAC1, HDAC2, and HDAC3) was also analyzed.
      Interestingly, the level of HDAC1 was aberrantly suppressed in TCE-treated L-02
      cells while enhanced in SET-knockdown L-02 cells. To further explore the
      potential role of HDAC1 in SET-mediated hepatic cytotoxicity of TCE, we employed
      RNA interference (RNAi) to knockdown HDAC1 in both wide type L-02 and SET
      knockdown cells. The results showed that the siRNA inhibition of HDAC1 increased
      the acetylation of H2AK9. Taken together, our data suggested that SET promoted
      the acetylation of H2AK9 via suppressing the level of HDAC1, which was involved
      in SET-mediated hepatic cytotoxicity of TCE.

PMID- 29579542
TI  - Nicorandil alleviates ovalbumin-induced airway inflammation in a mouse model of
      asthma.
AB  - Nicorandil is an antianginal drug that has anti-inflammatory property. This study
      aimed to investigate the effects of nicorandil on allergic asthma induced by
      ovalbumin (OVA) in mice in comparison with dexamethasone. Mice were sensitized to
      OVA (on days 0 and 7) and challenged with OVA three times (on days 14, 15 and
      16). Nicorandil was given orally for 5 days 1 h before OVA treatment in days of
      challenge. Progression of asthma was accompanied by significant elevation in the
      lung/body weight index, LDH, total protein, IL-13 and NF-kappaB levels besides
      inflammatory cell counts in BALF; Also pulmonary MDA and NO contents were
      significantly increased but GSH and SOD levels were decreased. Histopathological
      alterations in lung tissues were also observed. In contrast, nicorandil treatment
      significantly alleviated OVA-induced lung injury. In conclusion, our results
      proposed that nicorandil is equivalent to dexamethasone in ameliorating allergic
      asthma by restoring oxidant/antioxidant balance and reducing inflammation.

PMID- 29579543
TI  - IGFBP-3 plays an important role in senescence as an aging marker.
AB  - Aging study requires aging markers to measure the degree of aging process. The
      aging markers such as senescence associated-beta-galactosidase (SA-beta-gal),
      lipofuscin, telomere, p53 and p16 have been known in aging study until now.
      Therefore, we investigated the role of genes and proteins related to aging in
      young, senescent and H2O2-induced old cells to develop a novel aging marker
      involved in aging mechanism. After cellular aging was compared in young,
      senescent and H2O2-induced old cells using SA-beta-galactosidase staining assay,
      the expression level of genes and proteins in senescent and H2O2-induced old
      cells were compared and analyzed with those of young cells using RT-PCR, western
      blot and immunofluorescence staining. First of all, the senescent cells and the
      cells aged by H2O2 showed higher level of SA-beta-galactosidase staining than
      young cells. In particular, the expression level of IGFBP-3 was decreased in
      senescent and H2O2-induced old cells compared with young cells. Moreover, the
      senescent and H2O2-induced old cells showed higher expression levels of p-PI3K,
      Akt-1, p-mTOR, p-FoxO1 and FoxO1 than young cells. Furthermore, the expression
      levels of p300, Ac-p53, p53, p-p21 and p16 were significantly increased in
      senescent and H2O2-induced cells compared to young cells. However, the expression
      level of SIRT-1 was decreased in senescent and H2O2-induced old cells compared to
      young cells. In conclusion, IGFBP-3 up-regulates PI3K/Akt/mTOR signaling pathway
      and down-regulates autophagy during cell aging. These results suggest that IGFBP
      3 could play a key role in aging study as an important aging marker.

PMID- 29579544
TI  - Systems-synthetic biology in understanding the complexities and simple devices in
      immunology.
AB  - Systems and synthetic biology in the coming era has the ability to manipulate,
      stimulate and engineer cells to counteract the pathogenic immune response. The
      inherent biological complexities associated with the creation of a device allow
      capitalizing the biotechnological resources either by simply administering a
      recombinant cytokine or just reprogramming the immune cells. The strategy
      outlined, adopted and discussed may mark the beginning with promising
      therapeutics based on the principles of synthetic immunology.

PMID- 29579545
TI  - Increase in serum Interleukin-10 does not alleviate pro-inflammatory MCP-1
      production in obese pregnancies.
AB  - Maternal cytokine profiles during pregnancy are characterized by significant
      deviations, varying substantially between gestational time points and tissues.
      Obesity, in turn, is linked with low-grade inflammation in adipose tissue and
      increased concentrations of systemic inflammatory mediators. However, the balance
      of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive.
      In view of the demonstrations that the obesity is a global epidemic in the
      population at reproductive age with a strong intergenerational impact, we
      investigated the relation of gestational immune adaptations and obesity-induced
      inflammation. We found a significant decrease in systemic IL-1beta and MCP-1
      concentration from 1st to 3rd trimester of pregnancy while IL-10 concentration
      increased, respectively. However, in obese pregnancies this reduction of pro
      inflammatory mediators was not detected. This may constitute an additional risk
      factor in obese pregnancies in which the concentration of MCP-1 is already
      upregulated compared to normal weight mothers.

PMID- 29579546
TI  - Role of selective blocking of bradykinin B1 receptor in attenuating immune liver
      injury in trichloroethylene-sensitized mice.
AB  - Trichloroethylene (TCE) is able to induce trichloroethylene hypersensitivity
      syndrome (THS) with multi-system immune injuries. In our previous study, we found
      kallikrein-kinin system (KKS) activation, including the bradykinin B1 receptor
      (B1R), which contributed to immune organ injury in TCE sensitized mice. However,
      the mechanism of B1R mediating immune dysfunction is not clarified. The present
      study initiates to investigate the potential mechanism of B1R on liver injury. We
      establish a TCE sensitized BALB/c mouse model to explore the mechanism with or
      without a B1R inhibitor R715. We found B1R expression was increased in TCE
      sensitization-positive mice. As expect, hepatocyte intracellular organelles and
      mitochondria disappeared, glycogen particles reduced significantly as well in TCE
      sensitization-positive mice via the transmission electron microscopic
      examination, meanwhile, R715 alleviated the deteriorate above. The blockade of
      B1R resulted in a significant decreased p-ERK1/2 and increased p-AKT expression.
      The expression of CD68 kupffer cell and its relative cytokine, including IL-6 and
      TNF-alpha, increased in TCE sensitization-positive mice and decreased in R715
      pretreatment TCE sensitization-positive mice. Together, the results demonstrate
      B1R plays a key role in ERK/MAPK and PI3K/AKT signal pathway activation and
      inflammation cytokine expression in immune liver injury induced by TCE. B1R
      exerts a pivotal role in the development of TCE induced liver injury.

PMID- 29579547
TI  - Transfection of bone marrow derived cells with immunoregulatory proteins.
AB  - In vitro electroporation gene transfer was first performed in 1982. Today, this
      technology has become one of the major vehicles for non-viral transfection of
      cells. All non-viral transfections, such as calcium phosphate precipitation,
      lipofection, and magnetic transfection, have been shown to achieve a transfection
      efficiency of up to 70% in commonly used cell lines, but not in primary cells.
      Here we describe the use of electroporation to transfect primary mouse bone
      marrow-derived cells, such as macrophages (Mphi) and dendritic cells (DCs) with
      high efficiencies (45%-72%) and minimal cell death. The transfection efficiencies
      and cell death varied depending on the culture duration of the DCs and Mphi.
      Moreover, the electroporation efficiency was increased when conditioning medium
      was used for culturing the cells. Furthermore, we demonstrated that measuring the
      plasmid-encoded secreted proteins is a highly sensitive method for determining
      the transfection efficiency. In summary, electroporation with plasmid vectors is
      an efficient method for producing DCs and Mphi with transient expression of
      immunoregulatory proteins.

PMID- 29579548
TI  - Likelihood-based structural analysis of electron microscopy images.
AB  - Likelihood-based analysis of single-particle electron microscopy images has
      contributed much to the recent improvements in resolution. By treating particle
      orientations and classes probabilistically, uncertainties in the reconstruction
      process are explicitly accounted for, and the risk of bias towards the initial
      model is diminished. As a result, the quality and reliability of the
      reconstructions have greatly improved at manageable computational cost.
      Likelihood-based analysis of electron microscopy images also offers a route to
      direct coordinate refinement for dynamic systems, as an alternative to 3D density
      reconstruction. Here, we review recent developments in the algorithms used for
      reconstructions of high-resolution maps, and in the integrative framework of
      combining likelihood methods with simulations to address conformational
      variability in cryo-electron microscopy.

PMID- 29579549
TI  - Neighborhood collective efficacy, parental spanking, and subsequent risk of
      household child protective services involvement.
AB  - Children exposed to negative neighborhood conditions and parental spanking are at
      higher risk of experiencing maltreatment. We conducted prospective analyses of
      secondary data to determine the effects of neighborhood collective efficacy and
      parental spanking on household Child Protective Services (CPS) involvement, and
      whether spanking mediates the relationship between neighborhood collective
      efficacy and CPS involvement. The sample (N = 2,267) was drawn from the Fragile
      Families and Child Wellbeing Study (FFCWS), a stratified random sample of 4,789
      births between 1998-2000 in 20 large U.S. cities. Logistic regression models were
      employed to test the effects of neighborhood collective efficacy and spanking at
      child age 3 on mother's report of CPS contact during the subsequent two years.
      The product-of-coefficient approach was used to test the mediation hypothesis.
      One aspect of neighborhood collective efficacy (i.e., Social Cohesion/Trust) is
      associated with lower odds of CPS involvement (OR = .80, 95% CI 0.670-0.951)
      after controlling for Informal Social Control, parental spanking, and the
      covariates. Parental spanking predicts increased odds of CPS involvement during
      the next two years (OR = 1.38, 95% CI 1.001-1.898), net of neighborhood
      collective efficacy and the covariates. The mediation hypothesis is not
      supported. Promoting both cohesive and trusting relationships between neighbors
      and non-physical discipline practices is likely to reduce the incidence of
      household CPS involvement.

PMID- 29579550
TI  - Corrigendum to "Uptake and effects of a mixture of widely used therapeutic drugs
      in Eruca sativa L. and Zea mays L. plants" [Ecotoxicol. Environ. Saf. 108 (2014)
      52-57].

PMID- 29579551
TI  - Anti-GAD antibodies in a cohort of neuropsychiatric patients.
AB  - OBJECTIVE: Antiglutamate decarboxylase (anti-GAD) antibodies are associated with
      several neurological manifestations, like epilepsy and movement disorders.
      However, in daily neurological practice, it remains hard to define when to test
      for anti-GAD antibodies in patients with neurologic and/or psychiatric symptoms.
      Therefore, here, we report the patient characteristics of a large retrospective
      cohort of patients tested for anti-GAD antibodies in clinical practice and
      compare the characteristics of anti-GAD positive and anti-GAD negative patients.
      METHODS: We blindly assessed relevant clinical symptoms and comorbidities and
      functional outcome with the modified Rankin Scale (mRS) in a retrospective
      observational cohort of all patients in which the decision to assess anti-GAD
      levels had been made based solely on the presence of possible associated
      neurological and/or psychiatric symptoms (N=119). RESULTS: Out of 119 patients,
      17 (14.3%) were anti-GAD positive. The anti-GAD positive patients had a median
      age of 30years (range: 3-64; 2 children). They all had epilepsy, with 8 (47%)
      patients reporting cognitive complaints. Psychiatric symptoms were less prevalent
      in anti-GAD positive patients, only 1 anti-GAD positive patient (6%) versus 34
      anti-GAD negative patients (33%) reported psychiatric symptoms (p=0.021). The
      most frequent comorbidity of anti-GAD positive patients was diabetes mellitus
      type 1 (n=8). Twelve (71%) and 13 (78%) of the anti-GAD positive patients were
      functionally independent at the time of diagnosis and after one year,
      respectively (mRS score: 0 to 2). There was no significant difference in
      functional status at any time during follow-up compared with the anti-GAD
      negative group. CONCLUSION: Antiglutamate decarboxylase (anti-GAD) antibodies
      relate to epilepsy with or without cognitive complaints. However, psychiatric
      symptoms were almost absent in anti-GAD positive patients, and the presence of
      anti-GAD antibodies contributed little to the prognosis in our cohort.

PMID- 29579552
TI  - Proliferative hippocampal activity in a group of patients with Rasmussen's
      encephalitis: Neuronal, glial, and BDNF tissue expression correlations.
AB  - Rasmussen's encephalitis (RE) is a rare and devastating unilateral inflammatory
      brain disease that causes severe and intractable partial epilepsy. It has been
      shown that epilepsy and subsequent inflammation have deleterious influence on
      hippocampal cell survival and neurogenesis, but this still has not been
      systematically explored in human tissue. In this study, we investigated the
      correlation between inflammation and epilepsy as well as the rates of hippocampal
      gliogenesis and neurogenesis in a pediatric group of six patients with RE and six
      control cases. The dentate gyrus (DG) samples were obtained from patients who
      underwent surgery for intractable RE. Sections were processed for
      immunohistochemistry using antibodies against sex determining region Y-box 2
      (Sox2), nestin, human protein encoded by MKI67 gen (Ki67), and brain-derived
      neurotrophic factor (BDNF). There was an increase in the number of Ki67-positive
      granule cells in the DG of patients with RE in comparison with the autopsy
      control group, but no statistical difference for Sox2-positive cells was observed
      between these groups. Nestin immunolabeling was less intense in the RE group
      while BDNF expression was increased. Neurons that were BDNF-positive were found
      in DG from patients with RE but not in the control group. In patients with RE,
      few nestin-positive cells in DG were also positive for BDNF, unlike in controls
      which showed no colocalization for these two markers. These results suggest a
      proliferation activity in the DG subfield of patients with RE, and also future
      studies are necessary to address the role of new cells in the hippocampus of
      patients with RE.

PMID- 29579553
TI  - A systematic review of quality of life in parents of children with epilepsy.
AB  - OBJECTIVES: This systematic review aimed to 1) describe the quality of life (QOL)
      of parents of children with childhood-onset epilepsy (CWE), 2) identify factors
      associated with parental QOL, and 3) evaluate the association between parents'
      QOL and children's psychological well-being. METHODS: We conducted a
      comprehensive search of MEDLINE, EMBASE, and PsycINFO and conducted forward and
      backward citation tracking. A total of 15 articles met inclusion criteria.
      Parents' QOL was compared with population norms, healthy controls, and parents of
      children with other chronic conditions. Factors associated with parental QOL were
      systematically evaluated. RESULTS: Heterogeneity in study design and reporting
      prevented a meta-analytic synthesis of results. The majority of studies found
      that parents of CWE had poorer QOL relative to healthy controls or population
      norms and similar QOL as parents of children with other chronic conditions. In
      addition, poorer parental QOL was consistently associated with greater parental
      anxiety and depressive symptoms and poorer socioeconomic status and child QOL.
      Mothers had poorer QOL relative to fathers. Seizure control was not consistently
      associated with parental QOL. Results highlight the impact of family environment
      and psychosocial factors. SIGNIFICANCE: This review suggests that parents of CWE
      have compromised QOL. The results are in line with previous research showing the
      interdependent nature of psychosocial and medical factors, with psychosocial
      factors playing a critical role in child and parental QOL and well-being.
      Interventions targeting the family unit are warranted, and healthcare providers
      should be aware of the bidirectional relationship of epilepsy, family
      environment, and child/parent health and well-being.

PMID- 29579554
TI  - Clinical and electrophysiological findings in patients with phenylketonuria and
      epilepsy: Reflex features.
AB  - OBJECTIVE: Phenylketonuria (PKU) is the most common form of amino acid metabolism
      disorders with autosomal recessive inheritance. The brain damage can be prevented
      by early diagnosis and a phenylalanine-restricted diet. Untreated or late-treated
      patients may show mental retardation and other cognitive dysfunctions, as well as
      motor disability and/or epilepsy. METHODS: Three patients with PKU and epilepsy
      were recognized to have reflex epileptic features, and there were ten consecutive
      adult patients with PKU and epilepsy who were evaluated retrospectively. Medical
      history, ages at diagnosis and therapy onset, age at seizure onset, seizure types
      and reflex features, neurological findings, cranial imaging,
      electroencephalography (EEG) findings, and final clinical condition were
      evaluated. Reflex epilepsy features were examined in detail. RESULTS: The cases
      (6 females, 4 males) were diagnosed at ages between 3.5months and 12years. All
      patients had various degrees of mental-motor retardation and focal or generalized
      seizures with age at seizure onset varied between neonatal period and 15years.
      Three patients had febrile seizure, 3 patients had myoclonia, and 3 patients had
      status epilepticus. All patients had abnormal EEG findings except one. There was
      a slowing of background activity, and generalized discharges were observed in 7
      patients; 3 of them had asymmetrical discharges. One patient had right
      hippocampal sclerosis (HS), and another patient had hypointensities in the basal
      ganglia and corpus callosum. Reflex features were clinically observed in 3 of the
      patients; however, EEG results did not show any related findings. One patient had
      reflex seizures triggered by photic stimuli, hot water, and startling; one by
      photic stimuli; and the other one by startling. CONCLUSION: Reports on the
      clinical and electrophysiological features of adult patients with PKU were scant.
      We emphasized that reflex clinical features may be observed in this metabolic
      disease, and focal epileptiform abnormalities and asymmetry may be present in
      electrophysiological evaluation besides the rare association with HS.

PMID- 29579555
TI  - Mechanical behavior of surgical meshes for abdominal wall repair: In vivo versus
      biaxial characterization.
AB  - Despite the widespread use of synthetic meshes in the surgical treatment of the
      hernia pathology, the election criteria of a suitable mesh for specific patient
      continues to be uncertain. Thus, in this work, we propose a methodology to
      determine in advance potential disadvantages on the use of certain meshes based
      on the patient-specific abdominal geometry and the mechanical features of the
      certain meshes. To that purpose, we have first characterized the mechanical
      behavior of four synthetic meshes through biaxial tests. Secondly, two of these
      meshes were implanted in several New Zealand rabbits with a total defect
      previously created on the center of the abdominal wall. After the surgical
      procedure, specimen were subjected to in vivo pneumoperitoneum tests to determine
      the immediate post-surgical response of those meshes after implanted in a healthy
      specimen. Experimental performance was recorded by a stereo rig with the aim of
      obtaining quantitative information about the pressure-displacement relation of
      the abdominal wall. Finally, following the procedure presented in prior works
      (Simon-Allue et al., 2015, 2017), a finite element model was reconstructed from
      the experimental measurements and tests were computationally reproduced for the
      healthy and herniated cases. Simulations were compared and validated with the in
      vivo behavior and results were given along the abdominal wall in terms of
      displacements, stresses and strain. Mechanical characterization of the meshes
      revealed SurgiproTM as the most rigid implant and Neomesh SuperSoft(r) as the
      softer, while other two meshes (Neomesh Soft(r), Neopore(r)) remained in between.
      These two meshes were employed in the experimental study and resulted in similar
      effect in the abdominal wall cavity and both were close to the healthy case.
      Simulations confirmed this result while showed potential objections in the case
      of the other two meshes, due to high values in stresses or elongation that may
      led to discomfort in real tissue. The use of this methodology on human surgery
      may provide the surgeons with reliable and useful information to avoid certain
      meshes on specific-patient treatment.

PMID- 29579556
TI  - Variation of mechanical properties and oxidation with radiation dose and source
      in highly crosslinked remelted UHMWPE.
AB  - Ultra-high molecular weight polyethylene (UHMWPE) is the current gold standard
      for bearing materials used in total joint arthroplasty. High-dose radiation is
      commonly used to crosslink UHMWPE, thereby improving its wear resistance. A
      subsequent remelting step eliminates trapped residual free radicals to promote
      oxidative stability on the shelf, and to prevent material degradation over the
      long term. Assessment of clinically retrieved, highly crosslinked UHMWPE devices
      shows signs of unanticipated oxidation occurring in vivo, despite the absence of
      free radicals prior to implantation. These findings warrant further investigation
      into possible factors impacting this phenomenon along with its clinical
      implications. The overall objective of this work is to quantify the influence of
      irradiation dose and source on UHMWPE's oxidative stability, along with the
      effects of oxidation on the ultimate mechanical properties, including strength,
      ductility, and toughness. The results showed a strong positive correlation
      between maximum oxidation and initial transvinylene content. Critical oxidation
      levels in the context of mechanical property loss were determined for e-beam and
      gamma treatments at various radiation doses. Further, it was shown that critical
      oxidation was more dependent on radiation dose and less dependent on source. If
      in vivo oxidation persists in these devices, this can potentially lead to
      mechanical failure (e.g. fatigue damage) as observed in terminally gamma
      sterilized devices.

PMID- 29579557
TI  - Design of a hydraulically-driven bionic folding wing.
AB  - Membranous hind wings of the beetles can be folded under the elytra when they are
      at rest, and rotate and lift the elytra up only when they need to fly. This
      characteristic provides excellent flying capability and good environment
      adaptability. Inspired by the beetles, the new type of the bionic folding wing
      for the flapping wing Micro Air Vehicle (MAV) was designed. This flapping wing
      can be unfolded to get a sufficient lift in flight, and can be folded off flight
      to reduce the wing area and risk of the wing damage. The relationship between the
      internal pressures of the hydraulic system for the bionic wing folding varies and
      temperature was analyzed, the results show that the pressure within the system
      tends to increase with temperature, which proves the feasibility of the schematic
      design in theory. Stress analysis of the bionic wing was conducted, it was shown
      that stress distributions and deformation of the bionic wing under the positive
      and negative side loading are basically the same, which demonstrates that the
      strength of the bionic folding wing meets the requirements and further proves the
      feasibility of the schematic design.

PMID- 29579558
TI  - Does infant negative emotionality moderate the effect of maternal depression on
      motor development?
AB  - Maternal depression represents an important social/environmental factor in early
      childhood; however, its effect on children's motor development may vary depending
      on the role of infants' dispositional variables. The objective of this study is
      to investigate the effect of the interaction between maternal depressive symptoms
      in the first two years of a child's life and the child's temperamental negative
      emotionality on motor development during this time. Using a cross-sectional
      study, we assessed 272 infants aged 0 to 24 months old and their mothers. We
      measured the following variables: maternal depression, infant's negative
      emotionality, and motor development. A three-way interaction effect highlights
      that negative emotionality in infants and maternal depression together affect
      children's overall motor growth trajectory. Infants with low negative
      emotionality display no effect of maternal depression on motor development.
      Conversely, infants with high negative emotionality seem to be more susceptible
      to the effect of maternal depression. Specifically, high maternal depression
      tends to foster the negative effect of infant's negativity on motor development
      across time, albeit not significantly. Finally, the absence of maternal
      depression significantly buffers negative temperament in infants. Findings
      highlighted the importance of integrating different perspectives when describing
      early motor growth. In fact, only when considering the interdependence of
      potential predictors their effect on the motor growth significantly emerges.
      Screening for early temperamental vulnerability might help in tailoring
      interventions to prevent maternal depression from affecting infants' motor
      development.

PMID- 29579559
TI  - Attainment of gross motor milestones by preterm children with normal development
      upon school entry.
AB  - BACKGROUND: Little is known on the motor development of moderately preterm born
      (MPT) children, in comparison with early preterm born (EPT) children and fullterm
      born (FT), for children with normal motor outcomes at school entry. AIMS: To
      compare attainment rates of gross motor milestones reached between ages 1-24
      months for MPT, EPT, and FT children, all with normal development upon school
      entry. STUDY DESIGN: Prospective cohort study. SUBJECTS: We included 1247 preterm
      (PT) children (gestational age [GA] 24.0-35.6 weeks) and 488 FT children (GA 38.0
      41.6 weeks), with normal gross motor development at 4 years according to the Ages
      and Stages Questionnaire. OUTCOME MEASURES: We assessed 11 gross motor milestones
      assessed in preventive child healthcare during six standardized visits at
      calendar age. RESULTS: During the first six months, all PT categories had lower
      milestone attainment-rates than FTs children (differences 9-60% for PTs compared
      with FTs children). For all PT categories attainment rates gradually increased
      during toddlerhood. For PT children with higher GA, differences in attainment
      rates compared with FTs children were smaller and attainment rates became
      comparable to FT children at an earlier age. At age 24 months only attainment
      rates for PT children born <30 weeks GA remained lower than for FTs children (85%
      versus 95%, P < 0.01). CONCLUSION: Milestone attainment rates are highly
      dependent on GA during the first two years. Differences between PT and FT
      children are larger and persist longer with lower GA. For PT children <30 weeks
      GA, differences still occur at 24 months. CLINICAL TRIAL REGISTRY NAME AND
      REGISTRATION NUMBER: controlled-trials.com, ISRCTN 80622320.

PMID- 29579561
TI  - Time-resolved viscoelastic properties of self-assembling iron oxide nanocube
      superlattices probed by quartz crystal microbalance with dissipation monitoring.
AB  - Self-assembly of nanoparticles into superlattices can be used to create
      hierarchically structured materials with tailored functions. We have used the
      surface sensitive quartz crystal microbalance with dissipation monitoring (QCM-D)
      technique in combination with video microscopy (VM) to obtain time-resolved
      information on the mass increase and rheological properties of evaporation
      induced self-assembly of nanocubes. We have recorded the frequency and
      dissipation shifts during growth and densification of superlattices formed by
      self-assembly of oleic acid capped, truncated iron oxide nanocubes and analyzed
      the time-resolved QCM-D data using a Kelvin-Voigt viscoelastic model. We show
      that the nanoparticles first assemble into solvent-containing arrays dominated by
      a viscous response followed by a solvent-releasing step that results in the
      formation of rigid and well-ordered superlattices. Our findings demonstrate that
      QCM-D can be successfully used to follow self-assembly and assist in the design
      of optimized routes to produce well-ordered superlattices.

PMID- 29579560
TI  - Term-equivalent functional brain maturational measures predict neurodevelopmental
      outcomes in premature infants.
AB  - BACKGROUND: Term equivalent age (TEA) brain MRI identifies preterm infants at
      risk for adverse neurodevelopmental outcomes. But some infants may experience
      neurodevelopmental impairments even in the absence of neuroimaging abnormalities.
      OBJECTIVE: Evaluate the association of TEA amplitude-integrated EEG (aEEG)
      measures with neurodevelopmental outcomes at 24-36 months corrected age. METHODS:
      We performed aEEG recordings and brain MRI at TEA (mean post-menstrual age of 39
      (+/-2) weeks in a cohort of 60 preterm infants born at a mean gestational age of
      26 (+/-2) weeks. Forty-four infants underwent Bayley Scales of Infant
      Development, 3rd Edition (BSID-III) testing at 24-36 months corrected age.
      Developmental delay was defined by a score greater than one standard deviation
      below the mean (<85) in any domain. An ROC curve was constructed and a value of
      SEF90 < 9.2, yielded the highest sensitivity and specificity for moderate/severe
      brain injury on MRI. The association between aEEG measures and neurodevelopmental
      outcomes was assessed using odds ratio, then adjusted for confounding variables
      using logistic regression. RESULTS: Infants with developmental delay in any
      domain had significantly lower values of SEF90. Absent cyclicity was more
      prevalent in infants with cognitive and motor delay. Both left and right SEF90 <
      9.2 were associated with motor delay (OR left: 4.7(1.2-18.3), p = 0.02, OR right:
      7.9 (1.8-34.5), p < 0.01). Left SEF90 and right SEF90 were associated with
      cognitive delay and language delay respectively. Absent cyclicity was associated
      with motor and cognitive delay (OR for motor delay: 5.8 (1.3-25.1), p = 0.01; OR
      for cognitive delay: 16.8 (3.1-91.8), p < 0.01). These associations remained
      significant after correcting for social risk index score and confounding
      variables. CONCLUSIONS: aEEG may be used at TEA as a new tool for risk
      stratification of infants at higher risk of poor neurodevelopmental outcomes.
      Therefore, a larger study is needed to validate these results in premature
      infants at low and high risk of brain injury.

PMID- 29579562
TI  - Modification in supercapacitive behavior of CoO-rGO composite thin film from
      exposure to ferri/ferrocyanide redox active couple.
AB  - Present work demonstrates enhanced supercapacitive performance of CoO-rGO
      electrode using redox electrolyte. The long range electrostatic force developed
      during deposition of CoO-rGO composite thin film orient the molecules into the
      hexagonal crystal structure. The incorporated CoO particles into rGO nano-sheets
      make the structure more porous for the intercalation of the electrolyte ions
      through the electrode material. Additionally, 0.025 M K3[Fe(CN)6] + 0.025 M
      K4[Fe(CN)6] redox couple into KOH electrolyte enhances the supercapacitive
      performance than bare KOH electrolyte. The maximum specific capacitance of 1005 F
      g-1 is observed due to the combined effect of K3[Fe(CN)6] and K4[Fe(CN)6] redox
      couple into KOH electrolyte. Also, energy density of 86.74 Wh kg-1 at power
      density of 3.54 kW kg-1 suggest potential application of CoO-rGO composite thin
      film in the development of high energy density supercapacitor based on redox
      active electrolyte.

PMID- 29579563
TI  - Photo-induced surface modification to improve the performance of lead sulfide
      quantum dot solar cell.
AB  - The solution-processed quantum dot (QD) solar cell technology has seen
      significant advancements in recent past to emerge as a potential contender for
      the next generation photovoltaic technology. In the development of high
      performance QD solar cell, the surface ligand chemistry has played the important
      role in controlling the doping type and doping density of QD solids. For
      instance, lead sulfide (PbS) QDs which is at the forefront of QD solar cell
      technology, can be made n-type or p-type respectively by using iodine or thiol as
      the surfactant. The advancements in surface ligand chemistry enable the formation
      of p-n homojunction of PbS QDs layers to attain high solar cell performances. It
      is shown here, however, that poor Fermi level alignment of thiol passivated p
      type PbS QD hole transport layer with the n-type PbS QD light absorbing layer has
      rendered the photovoltaic devices from realizing their full potential. Here we
      develop a control surface oxidation technique using facile ultraviolet ozone
      treatment to increase the p-doping density in a controlled fashion for the thiol
      passivated PbS QD layer. This subtle surface modification tunes the Fermi energy
      level of the hole transport layer to deeper values to facilitate the carrier
      extraction and voltage generation in photovoltaic devices. In photovoltaic
      devices, the ultraviolet ozone treatment resulted in the average gain of 18% in
      the power conversion efficiency with the highest recorded efficiency of 8.98%.

PMID- 29579564
TI  - 2,2'-Dithiodisuccinic acid-stabilized polyion complex micelles for pH and
      reduction dual-responsive drug delivery.
AB  - In this work, a new kind of polyion complex (PIC) micelles with pH and reduction
      dual responsiveness was developed for effective intracellular drug delivery. The
      PIC micelles can be readily prepared by mixing a polycationic block polymer,
      methoxy poly(ethylene glycol)-b-poly(l-lysine) (mPEG-PLL), with a small molecule
      polyacid, 2, 2'-dithiodisuccinic acid (DTS) in aqueous media. The resultant PIC
      micelles are of uniform spherical shapes with hydrodynamic radii ranging from 65
      to 75 nm based on different feeding ratios of mPEG-PLL and DTS. Interestingly, by
      using the small molecule polyacid DTS, the obtained PIC micelles show distinct pH
      responsive disintegration in acid solution. Meanwhile, the PIC micelles were also
      assessed to be reduction-responsive due to the presence of disulfide bond in DTS.
      In view of these stimuli-responsive properties, the potential use of this PIC
      micelle as smart drug carrier was then investigated. Doxorubicin (DOX), a
      cationic anticancer drug, was loaded into the PIC micelles with high efficiency.
      In vitro drug release studies revealed that release of DOX from the PIC micelles
      was suppressed in neutral solutions due to the stable electrostatic interactions
      between PIC micelles and DOX, but could be accelerated in acidic solutions or
      under high GSH condition. Furthermore, flow cytometry and confocal laser scanning
      microscopy (CLSM) studies indicated that the DOX-loaded PIC micelles could be
      effectively internalized by MCF-7 human breast cancer cells and release the
      loaded DOX in intracellular environment. Consequently, the DOX-loaded PIC
      micelles were capable of inhibiting the proliferation of C26 murine colon cancer
      and MCF-7 human breast cancer cells in high efficiency, showing similar IC50
      values as free DOX. Thus, this biocompatible PIC micelle may be promising for
      intracellular drug delivery.

PMID- 29579565
TI  - Facile construction of novel direct solid-state Z-scheme AgI/BiOBr photocatalysts
      for highly effective removal of ciprofloxacin under visible light exposure:
      Mineralization efficiency and mechanisms.
AB  - A novel Z-scheme AgI/BiOBr hybrid photocatalyst was successfully synthesized by a
      solvothermal-precipitation method, and its photocatalytic activity was evaluated
      by the degradation of ciprofloxacin (CIP, a typical antibiotic). The
      crystallization, morphology, photo-response, surface structure and
      electrochemical properties of the as-obtained photocatalyst were characterized by
      XRD, XPS, SEM, TEM, BET, UV-Vis absorption spectroscopy and photoluminescence
      spectra (PL) measurements, respectively. The optimized AgI(20 wt%)/BiOBr
      composite exhibited a remarkable photocatalytic activity and a rapid degradation
      ability for CIP with a removal efficiency of 90.9% in 1 h, which was considerably
      better than those of pure BiOBr (58.6%) and pure AgI (4.6%) alone as well as
      their simple mixtures (31.4%) under the same conditions, suggesting an
      synergistic effect in the hybrid materials. Meanwhile, CIP was efficiently
      mineralized, as revealed by a total organic carbon (TOC) removal efficiency of
      ca. 90% within 2 h, which was further confirmed by the 3D EEMs measurement. The
      reactive species trapping and electron spin resonance (ESR) experiments
      demonstrated that O2-, h+ and OH all participated in the CIP photodegradation
      process. The photocatalytic mechanism of AgI/BiOBr composites could be rationally
      explained by considering the Z-scheme structure, resulting in the higher redox
      potential and more efficient separation of charge carriers. Moreover, the wider
      photo-response range induced by the photosensitization of AgI also contributed to
      the superior photocatalytic activity of the hybrid materials. This work reports a
      novel method for the facile preparation of Z-scheme AgI/BiOBr hybrid
      photocatalyst and provides an effective methodology for the mineralization of
      CIP.

PMID- 29579566
TI  - Fabrication of highly dispersed ultrafine Co9S8 nanoparticles on carbon
      nanofibers as low-cost counter electrode for dye-sensitized solar cells.
AB  - Platinum is the most commonly used dye-sensitized solar cell (DSSC) counter
      electrode (CE) due to its superior electrocatalytic activity and high
      transparency. However, the scarcity and high-cost of Pt restrict its practical
      application for the large-scale production of DSSCs. Herein, a facile approach
      for fabricating highly dispersed Co9S8 nanoparticles with small diameters in the
      range of 5-10 nm on the surface of carbon nanofibers (CNFs) via an
      electrospinning followed by calcination and hydrothermal reaction was developed.
      The composite material could be used as an efficient and low-cost Pt-free CE for
      DSSCs. The DSSC assembled with the prepared Co9S8/CNFs composite as a CE
      exhibited excellent electrocatalytic activity and a power conversion efficiency
      (PCE) of 8.37%, which is comparable to that of the DSSC with conventional
      thermally deposited Pt as the CE (8.50%). Therefore, the Co9S8/CNFs composite can
      be used as an efficient and low-cost promising alternative CE in DSSCs.

PMID- 29579567
TI  - Caring characters and professional identity among graduate nursing students in
      China-A cross sectional study.
AB  - BACKGROUND: Caring is recognized as the essence of nursing and the core of
      nursing practice while a positive professional identity can lead to personal,
      social and professional fulfillment. Analyzing caring characters and professional
      identity yields important indications for the improvement of teaching methods.
      This study aims to explore the graduate nursing students' professional identity
      and caring characters in China, and analyze their correlation. METHOD: A
      descriptive cross-sectional study was used to collect data from 216 graduate
      nursing students between January and February 2017 in China. RESULTS: Graduate
      nursing students perceived they possessed positive caring characters while their
      professional identity was at a low level. A significant positive correlation was
      found between the Nursing Caring Characters Assessment Tool and Professional
      Identity Scale for Nursing Students. CONCLUSION: Graduate nursing students'
      professional identity was not satisfactory and one strategy to improve this is to
      internalize caring into the education process. Nursing educators should focus
      more on the formation of the students' professional identity and caring as a
      contributing factor to it.

PMID- 29579568
TI  - Impact of a critical care postgraduate certificate course on nurses' self
      reported competence and confidence: A quasi-experimental study.
AB  - BACKGROUND: Postgraduate education is said to support the development of nurses'
      professional competence and confidence, essential to the delivery of safe and
      effective care. However, there is a shortness of empirical evidence to
      demonstrate an increase to nurses' self-reported confidence and competence on
      completion of critical care postgraduate certificate-level education. OBJECTIVES:
      To explore the impact of a critical care postgraduate certificate course on
      nurses' self-reported competence and confidence. To explore the psychometric
      properties and performance of the Critical Care Competence and Confidence
      Questionnaire. DESIGN: A quasi-experimental pre/post-test design. PARTICIPANTS: A
      total population sample of nurses completing a critical care postgraduate
      certificate course at an Australian University. METHODS: The Critical Care
      Competence and Confidence Questionnaire was developed for this study to measure
      nurses' self-reported competence and confidence at baseline and follow up.
      Descriptive and inferential statistics were used to explore sample
      characteristics and changes between baseline and follow-up. Reliability of the
      questionnaire was explored using Cronbach's Alpha and item-total correlations.
      RESULTS: There was a statistically significant increase in competence and
      confidence between baseline and follow-up across all questionnaire domains.
      Satisfactory reliability estimates were found for the questionnaire. CONCLUSIONS:
      Completion of a critical care postgraduate certificate course significantly
      increased nurses' perceived competence and confidence. The Critical Care
      Competence and Confidence Questionnaire was found to be psychometrically sound
      for measuring nurses' self-reported competence and confidence.

PMID- 29579569
TI  - Predictors of nurses' level of participation in student care: A multivariable
      analysis.
AB  - OBJECTIVE: To determine the association and predictive nature of certain socio
      demographic, education, work and research variables on nurses' participation
      level in the clinical care of students. DESIGN: A cross-sectional analytical
      study using a validated questionnaire between February and June 2014. SETTING AND
      PARTICIPANTS: A consecutive sample of 117 nurses who worked in public health
      centres in the province of Castellon (Spain) in 2014. The nurses who had never
      mentored students and the questionnaires that were <50% complete were excluded.
      METHODS: A descriptive analysis of the sample and an association analysis between
      variables were performed. The questionnaire and its dimensions were performed
      with a logistic regression and the maximum likelihood method, which used a
      complementary log-log link method. The concordance index was calculated using
      contingency tables. RESULTS: The mean age was 42.56 years, and the overall mean
      questionnaire score was 122.84 (SD = 18.69; 95% CI: 119.415-126.26). Across the
      sample, 58.1% (n = 68) of the nurses obtained an Excellent score, followed by
      Adequate in 41% (n = 48). Overall, the predictive variables were age, mentoring
      of students in the last 5 years and previous training to mentor students.
      CONCLUSION: The main predictive variable for greater participation in the
      mentorship of students was previous training in mentoring. This study also
      reflected on other variables that could influence nurses' participation in
      student mentoring.

PMID- 29579570
TI  - Nursing curriculum and bullying: An integrative literature review.
AB  - OBJECTIVES: The purpose of this integrative review was to identify and synthesize
      key concepts that inform curriculum which increase nursing students' competence,
      skills and strategies when addressing bullying. Specifically, the authors sought
      to examine the concepts informing educational interventions, skills, and
      strategies, which addressed the bullying of nursing students. DESIGN: Integrative
      literature review. DATA SOURCES: A search of the electronic databases CINAHL,
      MEDLINE, ERIC, PsycINFO, Proquest, and PubMed was conducted in January 2016 using
      search terms such as 'bully' 'nursing student' 'education' and 'curriculum'.
      REVIEW METHODS: Articles were screened for relevance and eligibility and
      extracted onto a table. Critical appraisal was conducted using multiple tools.
      Papers were analysed using constant comparison and concept mapping. RESULTS: 61
      articles were included in the synthesis. Concepts identified included:
      empowerment, socialization, support, self-awareness, awareness about bullying,
      collaboration, communication, and self-efficacy. All concepts linked to
      empowerment. Social Cognitive Theory was used by many studies. Active teaching
      methods which gave students opportunities to practice skills were the most
      effective. CONCLUSIONS: Empowered nursing students have the potential to address
      bullying more effectively and competently. Empowerment of nursing students is a
      powerful concept that educators must consider when developing curriculum and
      educational interventions to address bullying.

PMID- 29579571
TI  - Identifying reliable predictors of protein-energy malnutrition in hospitalized
      frail older adults: A prospective longitudinal study.
AB  - BACKGROUND: Decreased food intake is a risk factor for relevant complications
      (e.g. infections, pressure ulcers), longer hospital stays, higher readmission
      rates, greater health care costs and increased patient mortality, particularly in
      frail hospitalized older adults who are malnourished or at risk of malnutrition.
      Nurses are called to improve this criticality, starting from accurately
      identifying malnourished patients at hospital admission and effectively
      monitoring their food intake. OBJECTIVES: The primary aim was to identify
      reliable predictive indicators of reduced food intake at hospital admission. The
      secondary aims were to assess the adequacy of daily energy and protein intake and
      the impact of nutrient intake on patient outcomes. DESIGN: Prospective
      observational longitudinal study. SETTING: Internal Medicine Ward of an Academic
      Teaching University Hospital. PARTICIPANTS: Acute older adults who were
      malnourished or at risk of malnutrition (Nutritional Risk Score-2002 >= 3, middle
      upper arm circumference <23.5 cm or impaired self-feeding ability) at admission.
      METHODS: The effective energy and protein intake was monitored during the first 5
      days of hospital stay by a photographic method and compared to the daily energy
      and protein requirement calculated by specific equations. Data on anthropometry,
      inflammation/malnutrition laboratory data and body composition (phase angle
      calculated using bioelectrical impedance analysis) were collected. RESULTS:
      Eighty-one subjects (age 81.5 +/- 11.5 years) were enrolled. Mean energy intake
      was 669.0 +/- 573.9 kcal/day, and mean protein intake was 30.7 +/- 25.8 g/day.
      Over 60% of patients ingested <=50% of their calculated energy and protein
      requirements: these patients were older (p = 0.026), had a lower middle-upper arm
      circumference (p = 0.022) and total arm area (p = 0.038), a higher C-reactive
      protein/albumin ratio and Instant Nutritional Assessment score (p < 0.01), and
      experienced longer hospital stays (p <= 0.04) and higher in-hospital and 30-day
      post-discharge mortality (p < 0.001). In the multivariate analysis, lower middle
      upper arm circumference, higher C-reactive protein/albumin ratio, and impaired
      self-feeding at admission were independently associated with critically reduced
      energy and protein intake. CONCLUSIONS: Middle-upper arm circumference, C
      reactive protein/albumin ratio, and impaired self-feeding are easily obtainable
      indicators of impaired energy and protein intake and poor clinical outcomes. Such
      parameters should be adopted as screening criteria to assess the risk for
      critically reduced energy/protein intake in hospitalized older adults. These
      findings are relevant to improve clinical practice through the implementation of
      multidisciplinary strategies, given the adverse clinical outcomes related to
      hospital malnutrition.

PMID- 29579572
TI  - Impact of physician-less pediatric critical care transport: Making a decision on
      team composition.
AB  - PURPOSE: To explore the impact of a physician non-accompanying pediatric critical
      care transport program, and to identify factors associated with the selection of
      specific transport team compositions. MATERIALS AND METHODS: Children transported
      to a Canadian academic children's hospital were included. Two eras (Physician
      accompanying Transport (PT)-era: 2000-07 when physicians commonly accompanied the
      transport team; and Physician-Less Transport (PLT)-era: 2010-15 when a physician
      non-accompanying team was increasingly used) were compared with respect to
      transport and PICU outcomes. Transport and patient characteristics for the PLT
      era cohort were examined to identify factors associated with the selection of a
      physician accompanying team, with multivariable logistic regression with triage
      physicians as random effects. RESULTS: In the PLT-era (N=1177), compared to the
      PT-era (N=1490) the probability of PICU admission was significantly lower, and
      patient outcomes including mortality were not significantly different.
      Associations were noted between the selection of a physician non-accompanying
      team and specific transport characteristics. There was appreciable variability
      among the triage physicians for the selection of a physician non-accompanying
      team. CONCLUSIONS: No significant differences were observed with increasing use
      of a physician non-accompanying team. Selection of transport team compositions
      was influenced by clinical and system factors, but appreciable variation still
      remained among triage physicians.

PMID- 29579573
TI  - Cardiovascular ultrasonography detection of embolic sources in trauma.
AB  - Venous thromboembolism (deep vein thrombosis and pulmonary embolism) and bone
      cement implantation syndrome are major sources of embolic events in trauma
      patients. In these patients, embolic events due to venous thromboembolism and
      bone cement implantation syndrome have been detected with cardiac and vascular
      ultrasonography in the emergency setting, during the perioperative period, and in
      the intensive care unit. This article discusses the ultrasonography modalities
      and imaging findings of embolic events related to venous thromboembolism and bone
      cement implantation syndrome. The aim is to present a short review with
      exceptional illustrations that can enable physicians to identify sources of
      emboli in trauma patients with cardiovascular ultrasonography.

PMID- 29579575
TI  - To B or not to B: a tale of unorthodox chromosomes.

PMID- 29579574
TI  - Satellite DNA evolution: old ideas, new approaches.
AB  - A substantial portion of the genomes of most multicellular eukaryotes consists of
      large arrays of tandemly repeated sequence, collectively called satellite DNA.
      The processes generating and maintaining different satellite DNA abundances
      across lineages are important to understand as satellites have been linked to
      chromosome mis-segregation, disease phenotypes, and reproductive isolation
      between species. While much theory has been developed to describe satellite
      evolution, empirical tests of these models have fallen short because of the
      challenges in assessing satellite repeat regions of the genome. Advances in
      computational tools and sequencing technologies now enable identification and
      quantification of satellite sequences genome-wide. Here, we describe some of
      these tools and how their applications are furthering our knowledge of satellite
      evolution and function.

PMID- 29579576
TI  - Systematic review of efficacy and safety of retrievable inferior vena caval
      filters.

PMID- 29579577
TI  - Sniffing bacterial volatile compounds for healthier plants.
AB  - Bacterial volatile compounds (BVCs) are not waste or by-products of primary
      metabolism but rather have critical roles in the biology and ecological
      competence of bacteria. BVCs are exploited as a source of nutrients and
      information in plant-bacteria interactions. They target key points in plant
      physiology, activating downstream metabolic pathways by a domino effect. BVCs are
      an ancient signal and are involved in plant-bacteria communication, which was
      shaped during evolutionary history and established before the development of
      higher plants. This type of communication is not exclusive to mutualistic
      interactions, because pathogens also use volatiles to alter plant physiology.
      Here, fragmented information is drawn together to provide a clearer view of how
      BVCs affect such interactions.

PMID- 29579578
TI  - The molecular machines that traffic signaling receptors into and out of cilia.
AB  - Cilia are surface-exposed organelles that dynamically concentrate signaling
      molecules to organize sensory, developmental and homeostatic pathways. Entry and
      exit of signaling receptors is germane to the processing of signals and the
      molecular machines for entry and exit have started to emerge. The IFT-A complex
      and its membrane recruitment factor Tulp3 complex promotes the entry of signaling
      receptors into cilia while the BBSome and its membrane recruitment factor Arl6GTP
      ferry activated signaling receptors out of cilia. Ciliary exit is a surprisingly
      complex process entailing passage through a first diffusion barrier at the
      transition zone, diffusion inside an intermediate compartment and crossing of a
      periciliary diffusion barrier. The two barriers may organize a privileged
      compartment where activated signaling receptors transiently reside.

PMID- 29579580
TI  - Cost-effectiveness of a management strategy based on exercise echocardiography
      versus exercise electrocardiography in patients presenting with suspected angina
      during long term follow up: A randomized study.
AB  - INTRODUCTION: Exercise ECG (Ex-ECG) is advocated by guidelines for patients with
      low - intermediate probability of coronary artery disease (CAD). However, there
      are no randomized studies comparing Ex-ECG with exercise stress echocardiography
      (ESE) evaluating long term cost-effectiveness of each management strategy.
      METHODS: Accordingly, 385 patients with no prior CAD and low-intermediate
      probability of CAD (mean pre-test probability 34%), were randomized to undergo
      either Ex-ECG (194 patients) or ESE (191 patients). The primary endpoint was
      clinical effectiveness defined as the positive predictive value (PPV) for the
      detection of CAD of each test. Cost-effectiveness was derived using the
      cumulative costs incurred by each diagnostic strategy during a mean of follow up
      of 3.0 years. RESULTS: The PPV of ESE and Ex-ECG were 100% and 64% (p = 0.04)
      respectively for the detection of CAD. There were fewer clinic (31 vs 59, p <
      0.01) and emergency visits (14 vs 30, p = 0.01) and lower number of hospital bed
      days (8 vs 29, p < 0.01) in the ESE arm, with fewer patients undergoing coronary
      angiography (13.4% vs 6.3%, p = 0.02). The overall cumulative mean costs per
      patient were L796 for Ex-ECG and L631 for ESE respectively (p = 0.04) equating to
      a >20% reduction in cost with an ESE strategy with no difference in the combined
      end-point of death, myocardial infarction, unplanned revascularization and
      hospitalization for chest pain between ESE and Ex-ECG (3.2% vs 3.7%, p = 0.38).
      CONCLUSION: In patients with low to intermediate pretest probability of CAD and
      suspected angina, an ESE management strategy is cost-effective when compared with
      Ex-ECG during long term follow up.

PMID- 29579579
TI  - Deciphering functional glycosaminoglycan motifs in development.
AB  - Glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin/dermatan sulfate,
      and keratan sulfate are linear glycans, which when attached to protein backbones
      form proteoglycans. GAGs are essential components of the extracellular space in
      metazoans. Extensive modifications of the glycans such as sulfation,
      deacetylation and epimerization create structural GAG motifs. These motifs
      regulate protein-protein interactions and are thereby repsonsible for many of the
      essential functions of GAGs. This review focusses on recent genetic approaches to
      characterize GAG motifs and their function in defined signaling pathways during
      development. We discuss a coding approach for GAGs that would enable
      computational analyses of GAG sequences such as alignments and the computation of
      position weight matrices to describe GAG motifs.

PMID- 29579581
TI  - Midazolam addition to analgosedation for pulmonary vein isolation may increase
      risk of hypercapnia and acidosis.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) is generally performed under
      analgosedation, but sedation protocols vary and no optimal protocol has been
      defined. We investigated procedural, respiratory and hemodynamic parameters in
      patients undergoing PVI using analgosedation either with or without midazolam.
      METHODS: In a prospective observational study, we compared n = 43 consecutive
      patients (54% male, mean age 62 years) undergoing PVI using analgosedation either
      with or without midazolam added to propofol and fentanyl. A priori defined
      outcome measures were propofol dose, hypotension (systolic blood pressure <100 mm
      Hg or >30 mm Hg drop from baseline), acidosis (pH < 7.30), hypercapnia (pC02 > 55
      mm Hg) and hypoxemia (transdermal oxygen saturation < 90%). RESULTS: Patients in
      the midazolam group (n = 22) received a mean dose of 3 +/- 1.5 mg midazolam and
      required less propofol than those in the no-midazolam group (n = 21, 473 +/- 189
      mg vs. 618 +/- 219 mg, p = .03). Incidence of hypotension did not differ between
      groups (54.5% vs. 61.9%, p = .63). Acidosis was more frequent in the midazolam
      group (63.6% vs. 28.6%, p = .03), as was hypercapnia (50% vs. 14.3%, p = .03)
      while occurrence of hypoxemia did not differ between groups (22.7 vs. 33.3%, p =
      .5). CONCLUSION: Patients receiving midazolam had a more than doubled risk of
      respiratory depression as mirrored by hypercapnia and acidosis, but not
      hypoxemia. These observations may help in choosing an analgosedation and
      monitoring protocol for PVI.

PMID- 29579582
TI  - Non-vitamin K antagonist use in the cryoballoon technique using a purse-string
      suture closure.

PMID- 29579583
TI  - The role of electroanatomical mapping in individualized treatment of paroxysmal
      atrial fibrillation.

PMID- 29579584
TI  - Empirical cavotricuspid isthmus line for atrial fibrillation ablation is futile
      "Repetita Iuvant".

PMID- 29579585
TI  - Resting heart rate in late adolescence and long term risk of cardiovascular
      disease in Swedish men.
AB  - AIM: To investigate the association of resting heart rate (RHR) measured in late
      adolescence with the long term risk of myocardial infarction (MI), ischemic
      stroke (IS), heart failure (HF), atrial fibrillation (AF), cardiovascular- and
      all-cause death. METHODS AND RESULTS: We followed a cohort of Swedish men
      enrolled for conscription in 1968-2005 (n = 1,008,485; mean age = 18.3 years)
      until December 2014. Outcomes were collected from the national inpatient - (IPR),
      outpatient - (OPR) and cause of death registries. Cox proportional hazard models
      were used to analyze the longitudinal association between RHR and outcomes while
      adjusting for potential confounders. While we found no independent association
      between RHR and risk of IS or MI when comparing the highest with the lowest
      quintile of the RHR distribution, but a positive association persisted between
      RHR and incident HF (Hazard ratio (HR) = 1.39 [95% confidence interval (CI) =
      1.29-1.49]) after adjustment for body mass index (BMI) and blood pressure (BP).
      In similarly adjusted models, an inverse association was found for AF while there
      were weaker associations with death from cardiovascular disease (CVD) and all
      causes (adjusted HR = 1.12 [CI = 1.04-1.21] and 1.20 [CI = 1.17-1.24]). After
      further adjustment for cardiorespiratory fitness (CRF), the associations
      persisted for HF (HR = 1.26 [1.17-1.35] for any diagnostic position and HR = 1.43
      [1.28-1.60] for HF as a main diagnosis) and for all-cause death (HR 1.09 [1.05
      1.12]) but not for CVD death. CONCLUSION: Adolescent RHR is associated with
      future risk of HF and death, independently of BP, BMI and CRF, but not with CVD
      death, MI or IS, suggesting a causal pathway between elevated heart rate and
      myocardial dysfunction.

PMID- 29579586
TI  - Subclinical left ventricular dysfunction and correlation with regional strain
      analysis in myocarditis with normal ejection fraction. A new diagnostic
      criterion.
AB  - BACKGROUND: The diagnosis of myocarditis is challenging, especially in case of
      normal left ventricular systolic function. The aim of this study is to test the
      hypothesis that 2D speckle tracking echocardiography (2DSTE) can detect
      subclinical left ventricular (LV) dysfunction in patients with myocarditis and
      preserved LV function without regional wall motion abnormalities and that
      regional strain analysis can correlate with cardiac magnetic resonance (CMR)
      findings. METHODS: Study population consisted of 25 consecutive patients with
      myocarditis and 19 controls. All patients underwent a full echocardiographic
      study at the first day of their admission and in addition to conventional
      echocardiographic measurements, global longitudinal and circumferential strain of
      the left ventricle (LVGLS, LVCS accordingly), as well as regional strains of the
      lateral wall, were estimated. Moreover, all patients underwent a CMR scan during
      the first week from their admission. RESULTS: Although there was no statistical
      difference between the two groups of patients in systolic function, myocarditis
      patients demonstrated significantly impaired LVGLS (-16.5 +/- 2.2 vs -20.5 +/-
      1.3%, p < 0.0001) and LVCS (-16.4 +/- 3.7 vs -20.9 +/- 2%, p = 0.002), as well as
      segmental longitudinal strains of the lateral wall. CMR in all myocarditis
      patients revealed late gadolinium enhancement in the lateral left ventricle free
      wall. CONCLUSIONS: In patients with acute myocarditis with preserved ejection
      fraction, 2DSTE evaluation appears to be a promising, useful noninvasive and
      inexpensive tool in addition to existing methods used for the diagnosis of acute
      myocarditis, since it seems to be able to identify myocardial fibrosis early in
      the setting of the disease.

PMID- 29579587
TI  - A systematic review of clozapine-induced myocarditis.
AB  - BACKGROUND: Clozapine is an atypical antipsychotic that is beneficial to some
      patients who failed to have an adequate clinical response to other antipsychotic
      drugs. Its clinical use is limited due to several potentially fatal adverse
      reactions including myocarditis. Careful monitoring of patients on clozapine is
      required. METHODS: We conducted a systematic review of the literature on
      myocarditis associated with clozapine therapy. The search engines used to
      identify cases were MEDLINE, EMBASE, PsycINFO and Cochrane reviews. The
      references included in the manuscripts reviewed were searched to identify
      additional reports. RESULTS: We identified a total of 3347 articles that
      addressed the cardiac complications of clozapine. Of these, 82 articles detailed
      cases of clozapine-induced myocarditis. The median age of patients and dose of
      clozapine at presentation was 30years and 250mg/day respectively. Symptoms and
      signs of myocarditis developed in 87% of patients within the first month of
      treatment. Clinical presentation included: shortness of breath (67%), fever (67%)
      and tachycardia (58%). Cardiac markers were elevated in 87% of the 54 cases that
      reported these markers. Global ventricular dysfunction was the predominant
      echocardiogram finding (57%). CONCLUSIONS: Patients on clozapine require routine
      monitoring for symptoms and signs of myocarditis during the first three months of
      therapy. This adverse drug reaction is difficult to diagnose due the non-specific
      nature of the symptoms and signs. Alternate causes of myocarditis should be ruled
      out before attributing the myocarditis to clozapine.

PMID- 29579588
TI  - Clozapine-induced myocarditis: "Psychoanalysing" drug-induced myocarditis.

PMID- 29579589
TI  - The (ultra) sound of a burning heart: A matter of speckles.

PMID- 29579590
TI  - Right ventriculo-arterial coupling in heart failure: The role of the
      interventricular septum.

PMID- 29579591
TI  - Right ventriculo-arterial coupling in heart failure - Is the right ventricle
      independent?

PMID- 29579592
TI  - Why is PAP guided therapy effective?

PMID- 29579594
TI  - Comparing cardioprotetion by DiOHF intervention and ischemic preconditioning.

PMID- 29579593
TI  - AMP-activated protein kinase protects against necroptosis via regulation of Keap1
      PGAM5 complex.
AB  - BACKGROUND: The AMP-activated protein kinase (AMPK) plays critical roles in
      growth regulation and metabolism reprogramming. AMPK activation protects cells
      against apoptosis from injury in different cell and animal models. However, its
      function in necroptosis remains largely unclear. METHODS AND RESULTS: In the
      current study, we demonstrated that AMPK was activated upon necroptosis induction
      and protected mouse embryonic fibroblasts (MEFs) and cardiomyocytes from N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) and reactive oxygen species (ROS) induced
      necroptosis. Activation of AMPK with chemicals A-769662, 2-deoxyglucose (2-DG),
      and metformin or constitutively active (CA) AMPK markedly decreased necroptosis
      and cytotoxicity induced by MNNG. In contrast, AMPK inhibitor compound C,
      dominant negative (DN) AMPK, as well as AMPK shRNAs increased necroptosis and
      cytotoxicity induced by MNNG. We further showed that AMPK physically associated
      with a protein complex containing PGAM5 and Keap1 whereby facilitating Keap1
      mediated PGAM5 ubiquitination upon necroptosis induction. The AMPK agonist
      metformin ameliorated myocardial ischemia and reperfusion (IR) injury and reduced
      necroptosis through down-regulating the expression of PGAM5 in the Langendorff
      perfused rat hearts. CONCLUSION: Activation of AMPK protects against necroptosis
      via promoting Keap1-mediated PGAM5 degradation. Metformin may act as a valuable
      agent for the protection of myocardial ischemia and reperfusion injury by
      activating AMPK and reducing necroptosis.

PMID- 29579595
TI  - Glycogen synthase kinase 3beta helps heart to pump better in obese patients.

PMID- 29579596
TI  - AMP-activated kinase "Keaps" ischemia/reperfusion-induced necroptosis under
      control.

PMID- 29579597
TI  - Physiological insights of exercise hyperventilation in arterial and chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) patients show, during exercise, an
      excessive increase in ventilation (VE) compared to carbon dioxide output (VCO2),
      determining a high VE/VCO2 slope. There are several possible causes, including an
      elevated dead space ventilation (VD), VE/perfusion (Q) mismatch and/or an
      enhanced peripheral or central chemoreceptor activity. We evaluated the causes of
      exercise hyperventilation in PH patients. METHODS: Eighteen group I and IV PH
      patients underwent cardiopulmonary exercise test with blood gas analysis at every
      minute. VE, alveolar ventilation (VA) and VD vs. VCO2 relationship were
      calculated. Resting chemoreceptor sensitivity was analyzed through
      hypoxia/hypercapnia tests. RESULTS: PeakVO2 and VE/VCO2 slopes were 1.06+/
      0.24l/min and 39.1+/-9.0, respectively. Throughout the exercise, 30% of VE was
      due to VD. VE/VCO2 slope significantly correlated with VD/VCO2 slope (r=0.82,
      p<0.001) but not with VA/VCO2 slope (r=0.3, p=ns). Peak exercise end-tidal CO2
      (PetCO2) correlated with VD/VCO2 slope (r=-0.79, p<0.001) and VE/VCO2 slope (r=
      0.91, p<0.001). Dead space(DS)/Tidal volume and P(arterial-et)CO2 were elevated
      without arterial hypoxemia suggesting a high VE/Q mismatch. Chemoreceptor
      peripheral response to hypoxia and central CO2 response were both enhanced being
      peripheral responses to hypoxia and hypercapnia 0.416+/-0.402 (normal ref
      values=0.285+/-0.221) l/min/O2Sat and 0.076+/-0.047 (0.066+/-0.430) l/min/mmHg,
      respectively; central hypercapnic chemosensitivity was 4.475+/-3.99 (2.352+/
      0.936) l/min/mmHg. CONCLUSIONS: Increased DS, VE/Q mismatch and chemorecptor
      response are among the main mechanisms involved in exercise hyperventilation in
      PH. ClinicalTrial.govNCT02892981.

PMID- 29579598
TI  - The breathlessness of pulmonary hypertension.

PMID- 29579599
TI  - Letter to "Correlation between pulmonary artery pressure and thoracic impedance:
      Insights from daily monitoring through an implanted device in chronic heart
      failure".

PMID- 29579600
TI  - Inflammatory biomarker profiling in classical orthostatic hypotension: Insights
      from the SYSTEMA cohort.

PMID- 29579601
TI  - Circulating Interleukin-6 is a biomarker for coronary atherosclerosis in
      nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND: Biomarkers to predict the presence and severity of subclinical
      cardiovascular disease (CVD) in nonalcoholic fatty liver disease (NAFLD) are
      lacking. METHODS: 3876 participants from the Multi-Ethnic Study of
      Atherosclerosis (MESA), without known chronic liver disease underwent baseline
      non-contrast cardiac CT, with NAFLD defined by validated liver:spleen ratio (L:S)
      < 1.0, and subclinical CVD defined by coronary artery calcium (CAC) score > 0.
      Randomly-selected subgroups underwent detailed inflammatory marker testing,
      including LpPLA2 mass (N = 2951), activity (N = 3020), high-sensitivity C
      reactive protein (hsCRP; N = 3849), and interleukin-6 (IL-6; N = 3764). Among
      those with NAFLD, we estimated the prevalence of CAC > 0 and CAC > 100 for each
      SD biomarker increase, using multivariable log-binomial regression models
      adjusted for cardiometabolic risk factors. RESULTS: Seventeen percent (N = 668)
      of participants met the criteria for NAFLD. NAFLD participants were younger (mean
      age 61 +/- 10 vs. 63 +/- 10 years, p < .0001) but more likely to have an elevated
      BMI (mean 31.1 +/- 5.5 vs. 28.0 +/- 5.2 kg/m2, p < .0001), diabetes (22% vs. 11%,
      p < .0001), and increased inflammatory biomarkers, including LpPLA2 activity,
      hsCRP and IL-6 (all p < .0001). Among NAFLD participants, IL-6 was the only
      biomarker independently associated with prevalent CAC > 0 (PR = 1.06 [1.00
      1.11]), or CAC > 100 (PR = 1.09 [1.02-1.17]). In contrast, circulating LpPLA2
      mass/activity and hsCRP were not associated with either the prevalence or
      severity of subclinical CVD (all p > .05). CONCLUSION: In a large, multi-ethnic
      population with NAFLD, IL-6 is independently associated with the prevalence and
      severity of subclinical atherosclerosis. Further research into the longitudinal
      effects of NAFLD on progressive CVD will determine whether IL-6 is a marker or
      mediator of NAFLD-related atherosclerosis.

PMID- 29579602
TI  - High on-treatment platelet reactivity and outcome in elderly with non ST-segment
      elevation acute coronary syndrome - Insight from the GEPRESS study.
AB  - BACKGROUND: Elderly treated with dual antiplatelet therapy after percutaneous
      coronary intervention (PCI) represent a challenging population because of
      increased risk of both ischemic and bleeding events. We aimed to investigate the
      association between high on-treatment platelet reactivity (HPR) and long-term
      outcome in elderly with non-ST-elevated acute coronary syndromes (NSTE-ACS)
      undergoing PCI. METHODS: Platelet reactivity was measured by vasodilator
      stimulated phosphoprotein (VASP) assay at three time-points (baseline, discharge,
      1 month after PCI) in 1053 NSTE-ACS patients (311 elderly) treated with
      clopidogrel. Major adverse cardiac events (MACE) were assessed up to 1 year
      follow-up. RESULTS: Elderly with HPR at discharge showed a significantly higher
      incidence of overall MACE (13 vs 4%, p = .006), cardiac death (6 vs 0.7%, p =
      .020), myocardial infarction (MI, 12 vs 4%, p = .031) and a trend for higher
      stent-thrombosis (5 vs 0.7%, p = .068). Similarly, elderly with 1-month-HPR
      showed between 1 month and 1 year significantly higher incidence of MACE (10 vs
      4%, p = .012), cardiac death (6 vs 0.7%, p = .019) and composite cardiac death/MI
      (11 vs 4%, p = .014). Up to 1 year, elderly with HPR showed a 4-fold increased
      risk of MACE compared to both elderly without HPR (for discharge-HPR: p = .005;
      for 1-month-HPR: p = .01) and non-elderly with HPR (for discharge-HPR: p < .001;
      for 1-month-HPR: p < .0001). At multivariable analysis, HPR could independently
      predict 1-year-MACE in elderly (for discharge-HPR: HR = 3.191, CI: 1.373-7.417, p
      = .007; for 1-month-HPR: HR = 3.542, CI: 1.373-9.137, p = .009). CONCLUSIONS: In
      elderly with NSTE-ACS undergoing PCI and treated with clopidogrel, HPR was
      independently associated with an increased risk of MACE up to 1 year.

PMID- 29579603
TI  - Biomarkers in orthostatic hypotension: The answer or just more questions?

PMID- 29579604
TI  - All roads lead to IL-6: A central hub of cardiometabolic signaling.

PMID- 29579605
TI  - Big data analysis from Sweden confirms that resting heart rate in late
      adolescence is significantly associated with incident heart failure and all-cause
      mortality.

PMID- 29579606
TI  - Higher levels of circulating naive CD8+CD45RA+ cells are associated with lower
      extent of coronary atherosclerosis and vascular dysfunction.

PMID- 29579607
TI  - Development and validation of Women Acute Myocardial Infarction in-Hospital
      Mortality Score (WAMI Score).
AB  - BACKGROUND: A variety of risk models have been developed to predict acute
      myocardial infarction (AMI) in-hospital mortality risk. As a distinct, higher
      risk population, women with AMI have different risk profiles from their men
      counterparts. Published researches have indicated that the interaction between
      variables in these models for in-hospital mortality and gender are significant.
      Due to the interaction and gender differences, the predicting value of these risk
      models for women could be controversial. METHODS: Databases from the China
      Patient-centered Evaluative Assessment of Cardiac Events (China PEACE)
      Retrospective AMI Study were utilized for model derivation (n=16,100, women were
      4896) and databases from the China PEACE Prospective AMI Study for model
      validation (n=6207, women were 2090). A multivariable backward stepwise logistic
      regression was used to examine correlates of in-hospital mortality, and the
      variables were subsequently weighted and integrated into a scoring system.
      RESULTS: We constructed a novel risk-predicting tool to estimate the baseline
      risk of in-hospital mortality among women with AMI. The risk score includes 8
      variables [age, systolic blood pressure, heart rate, initial glomerular
      filtration rate (GFR), serum glucose, Killip class, cardiac arrest, ventricular
      tachycardia/ventricular fibrillation (VT/VF)]. The prognostic discriminatory
      capacity of the Women Acute Myocardial Infarction in-Hospital Mortality (WAMI)
      risk score was excellent (c statistic 0.84, 95% confidence interval [CI]: 0.83 to
      0.86, p<0.001). External validation of the model showed better prognostic
      capacity (c statistic 0.87, 95% CI: 0.84 to 0.90, p<0.001) than the GRACE risk
      score (0.77, 95% CI 0.72-0.82, p<0.001) and TIMI risk score (0.72, 95% CI 0.68
      0.77, p<0.001). CONCLUSIONS: The WAMI Score is a simple robust tool for
      predicting the in-hospital mortality risk of women with AMI. TRIAL REGISTRATION:
      "China PEACE-Retrospective AMI Study", NCT01624883, retrospectively registered:
      April 2012. Date of enrolment of the first participant to the trial: June 17,
      2012. "China PEACE-Prospective AMI Study", NCT01624909, prospectively registered:
      December 2012. Date of enrolment of the first participant to the trial: June 17,
      2012.

PMID- 29579608
TI  - Stress echocardiography: time for a reassessment?

PMID- 29579609
TI  - Optimal antiplatelet therapy after an acute coronary syndrome in the elderly: An
      old issue.

PMID- 29579610
TI  - The saga of atherothrombosis and T-cells: Looking for the lost prologue.

PMID- 29579611
TI  - A new risk stratification tool for women with acute coronary syndrome.

PMID- 29579612
TI  - The microvascular network connecting extracardiac arteries to the heart.

PMID- 29579613
TI  - Response to letter from Piciche: The microvascular network connecting
      extracardiac arteries to the heart.

PMID- 29579614
TI  - How should we assess the performance of biodegradable polymer?

PMID- 29579615
TI  - Second-generation cryoballoon ablation as a first-line treatment of symptomatic
      atrial fibrillation: Two-year outcome and predictors of recurrence after a single
      procedure.
AB  - INTRODUCTION: Antiarrhythmic drug (AAD) therapy of patients with atrial
      fibrillation (AF) has limitations. We investigated the 2-year outcome and pre
      procedural predictors of recurrence for first-line catheter ablation using the
      second-generation cryoballoon (CB-Adv) in a large cohort of patients with
      symptomatic AF. METHODS AND RESULTS: For this prospective observational study, we
      enrolled 457 patients with symptomatic AF (278 paroxysmal, 179 persistent) who
      had no history of AAD use and who underwent pulmonary vein isolation (PVI) with
      the CB-Adv at our institution. Follow-up data, including Holter-ECGs, were
      collected during outpatient clinic visits. The impact of several variables on
      outcome was evaluated in univariate and multivariate analyses and Cox
      proportional hazards regression models. Median follow-up duration was 28
      (interquartile range 15/42) months. PVI was sufficient in restoring and
      maintaining sinus rhythm in 79.2% (n=362) of patients. The median procedure and
      fluoroscopy times were 90 (72/120) and 16 (12/21) min, respectively. Phrenic
      nerve injury occurred in 16 (3.5%) patients, persisting until hospital discharge
      in 6 (1.3%) patients; phrenic nerve function recovered in all patients during
      follow-up. Seven patients developed groin hematomas (1.5%). Cox regression
      analysis showed that left atrial area >21cm2 independently predicted recurrence.
      CONCLUSION: This is the first demonstration that PVI with CB-Adv is safe and
      effective as a first-line treatment of symptomatic AF. Sinus rhythm persisted in
      79.2% of patients even 2years after ablation. The success rate was lower in
      patients with enlarged left atria.

PMID- 29579616
TI  - Impact of prophylactic cavotricuspid isthmus ablation in atrial fibrillation
      recurrence after a first pulmonary vein isolation procedure.
AB  - INTRODUCTION: PVI is a well-established therapy for patients with drug refractory
      atrial fibrillation (AF). However, it remains unclear whether prophylactic
      cavotricuspid isthmus (CTI) ablation at the time of PVI improves long-term
      freedom from AF. OBJECTIVE: To compare the outcomes of patients who underwent PVI
      alone vs. PVI + prophylactic CTI ablation. METHODS: Propensity score (PS)
      matching analysis based on a registry dataset of 1931 consecutive patients who
      underwent a first AF catheter ablation. After excluding those with
      documented/inducible atrial flutter (n = 233), 1698 individuals were available
      for matching. Following adjustment for age, gender, body mass index (BMI),
      hypertension, smoking, diabetes, LA volume, type of AF, and type of navigation
      (magnetic vs. manual), PS matched 411 patients who underwent PVI + CTI ablation
      with 411 receiving PVI alone. RESULTS: PS analysis yielded a study population of
      822 matched patients (58 +/- 11 years, 69% males, 64% with paroxysmal AF). Over a
      median 2 years follow-up period there were 278 AF recurrences (34%). Survival
      free of AF (Log rank p = .965) and annual relapse rates were similar in the two
      groups - 10.9%/year vs 10.1%/year (PVI vs PVI + CTI, respectively, p = .97). CTI
      ablation remained unassociated with AF-free survival (HR 1.09, 95%CI: 0.84-1.41,
      p = .54) after Cox regression adjustment for age, sex, type of AF, LA volume,
      hypertension, diabetes, BMI and center. Female gender, current smoking, indexed
      LA volume and non-paroxysmal AF were identified as independent predictors of
      relapse after matching. CONCLUSIONS: Prophylactic CTI ablation at the time of a
      first PVI does not seem to improve long-term freedom from AF.

PMID- 29579618
TI  - Fluorescence-guided surgery of cancer: applications, tools and perspectives.
AB  - Thousands of patients die each year from residual cancer that remains following
      cytoreductive surgery. Use of tumor-targeted fluorescent dyes (TTFDs) to
      illuminate undetected malignant tissue and thereby facilitate its surgical
      resection shows promise for reducing morbidity and mortality associated with
      unresected malignant disease. TTFDs can also improve i) detection of recurrent
      malignant lesions, ii) differentiation of normal from malignant lymph nodes, iii)
      accurate staging of cancer patients, iv) detection of tumors during
      robotic/endoscopic surgery (where tumor palpation is no longer possible), and v)
      preservation of healthy tissue during resection of cancer tissue. Although TTFDs
      that passively accumulate in a tumor mass provide some tumor contrast, the most
      encouraging TTFDs in human clinical trials are either enzyme-activated or ligand
      targeted to tumor-specific receptors.

PMID- 29579617
TI  - Benefits of left ventricular endocardial pacing comparing failed implants and
      prior non-responders to conventional cardiac resynchronization therapy: A
      subanalysis from the ALSYNC study.
AB  - OBJECTIVE: Cardiac resynchronisation therapy (CRT) is limited by a substantial
      proportion of non-responders. Left ventricular endocardial pacing (LVEP) may
      offer enhanced possibility to deliver CRT in patients with a failed attempt at
      implantation and to improve clinical status of CRT non-responders. METHODS: The
      ALternate Site Cardiac ResYNChronisation (ALSYNC) study was a prospective, multi
      centre cohort study that included 118 CRT patients with a successfully implanted
      endocardial left ventricular (LV) lead, including 90 failed coronary sinus (CS)
      implants and 28 prior non-responders who had worsened or unchanged heart failure
      status after at least 6 months of optimal conventional CRT therapy. RESULTS:
      Patients were followed for 19 +/- 9 months. At baseline, prior non-responders
      were sicker as evidenced by a larger LV end-diastolic diameter (70 +/- 12 vs 65
      +/- 9 mm, p = .03) and a trend towards larger LV end-systolic volume index
      (LVESVi, 95 +/- 51 vs 74 +/- 39 ml/m2, p = .07), and were more frequently anti
      coagulated (96% vs 72%, p = .008) despite similar history of atrial fibrillation
      (54% vs 51%, p = .83). At 6 months, LVEP significantly improved LV ejection
      fraction (2.3 +/- 7.5 and 8.6 +/- 10.0%), New York Heart Association Class (0.4
      +/- 0.9 and 0.7 +/- 0.8), LVESVi (9 +/- 16 and 18 +/- 43 ml/m2), and six-minute
      walk test (56 +/- 73 and 54 +/- 92 m) in prior non-responders and failed CS
      implants, relative to baseline (all p < .05), respectively. LVESVi reduction
      >=15% was seen in 47% of the prior non-responder patients and 57% of failed CS
      patients. CONCLUSION: These data suggest that a sizable proportion of CRT non
      responders can improve by LVEP, though to a lesser extent than failed CS
      implants. Clinical trial registration-URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01277783.

PMID- 29579619
TI  - Epigenetic small molecule modulators of histone and DNA methylation.
AB  - DNA and histone methylation belong to the key regulatory components in the
      epigenetic machinery, and dysregulations of these processes have been associated
      with various human diseases. Small molecule modulators of these epigenetic
      targets are highly valuable both as chemical probes to study the biological roles
      of the target proteins, and as potential therapeutics. Indeed, recent years have
      seen the discovery of chemical modulators of several epigenetic targets, some of
      which are already marketed drugs or undergoing clinical trials. In this review,
      we will focus on small molecule modulators of DNA and histone methylation.

PMID- 29579620
TI  - Ground reaction forces during a drop vertical jump: Impact of external load
      training.
AB  - External load training (ELT) is a supplemental training method used to
      potentially improve high intensity task performance. However, biomechanical
      parameters such as ground reaction forces (GRF), ground contact time, and time to
      peak GRF during a drop vertical jump (DVJ) following an ELT intervention have yet
      to be examined. Therefore, this study investigated the impact of ELT on certain
      biomechanical parameters of a DVJ task. Well-trained females stratified into two
      groups (ELT = 9, Control = 10) completed a DVJ from a 45.72 cm box onto a force
      platform at baseline, post-ELT, and post-detraining (DET). ELT consisted of
      wearing weight vests (WV) with 8% body mass for 32 h/week during daily living and
      3 training sessions/week for 3 weeks. After ELT, a 3 week DET phase was
      completed. The control group replicated procedures without ELT intervention. The
      vertical, medial/lateral, and anterior/posterior components of the GRF were
      assessed during the initial contact, minimum force following initial contact,
      push-off, and second landing periods. Dependent variables were analyzed using a 2
      (group) * 3 (time) mixed model ANOVA (p < .05). Significantly greater peak
      vertical GRF during the initial contact period was identified for the ELT group.
      Significant increases in the minimum vertical GRF following the initial contact
      period from baseline to post-ELT following the were observed for the ELT group,
      while significant increases in peak vertical GRF during the second landing period
      at post-ELT and post-DET in comparison to baseline was observed for both groups.
      The combination of greater vertical GRF during the initial contact period and the
      period following initial contact suggests that ELT may increase GRFs during a DVJ
      in comparison to routine training without a weighted vest.

PMID- 29579621
TI  - The effects of dual tasking on gait synchronization during over-ground side-by
      side walking.
AB  - Recent studies have shown that gait synchronization during natural walking is not
      merely anecdotal, but it is a repeatable phenomenon that is quantifiable and is
      apparently related to available sensory feedback modalities. However, the
      mechanisms underlying this phase-locking of gait have only recently begun to be
      investigated. For example, it is not known what role, if any, attention plays. We
      employed a dual tasking paradigm in order to investigate the role attention plays
      in gait synchronization. Sixteen pairs of subjects walked under six conditions
      that manipulated the available sensory feedback and the degree of difficulty of
      the dual task, i.e., the attention. Movement was quantified using a trunk-mounted
      tri-axial accelerometer. A gait synchronization index (GSI) was calculated in
      order to quantify the degree of synchronization of the gait pattern. A simple
      dual task resulted in an increased level of synchronization, whereas a more
      complex dual task lead to a reduction in synchronization. Handholding increased
      synchronization, compared to the same attention condition without handholding.
      These results indicate that in order for two walkers to synchronize, some level
      of attention is apparently required, such that a relatively complex dual task
      utilizes enough attentional resources to reduce the occurrence of
      synchronization.

PMID- 29579622
TI  - Engineering T cells for adoptive therapy: outsmarting the tumor.
AB  - Adoptive transfer of T cells gene-engineered with antigen-specific receptors,
      whether it be chimeric antigen receptors (CARs) or T cell receptors (TCRs), has
      proven its feasibility and therapeutic potential in the treatment of tumors.
      Despite clinical successes, the majority of patients experiences no or non
      sustainable clearance of solid tumors, which is attributed to local T cell
      evasive mechanisms. A rapidly expanding understanding of molecular and cellular
      events that contribute to a reduction in numbers and/or activation of intra-tumor
      T cells has facilitated the development of gene-engineering strategies, enabling
      T cells to counter immune tolerance. Here, we present an overview of gene
      engineering approaches and considerations to improve tumor-selectivity and
      effectiveness of adoptively transferred T cells.

PMID- 29579623
TI  - Chemokines and cancer: new immune checkpoints for cancer therapy.
AB  - The current review focuses on two chemokine-chemokine receptor interactions:
      CXCL10-CXCR3 and CCL1-CCR8. We show that CXCL10 acts on CD4+ and CD8+ T cells to
      enhance anti-tumor immunity, and explore the translational perspectives of these
      findings. As for CCR8 very recently, we identified a novel subset of
      CCR8+CD4+FOXp3+ regulatory T cells (Treg) that are major drivers of immune
      regulation. We observed that one of the four CCR8 ligands, CCL1, produced by
      these cells, potentiates their suppressive activity via induction of CCR8, FOXp3,
      CD39, Granzyme-B, and IL-10 in a positive feedback mechanism, making them master
      drivers of immune regulation. Collectively, this suggests blocking the CCR8-CCL1
      interaction, alone or combined with other immune checkpoint inhibitors, as an
      approach to treat malignant diseases.

PMID- 29579624
TI  - Modulating ion channel function with antibodies and nanobodies.
AB  - Immune cells express various voltage-gated and ligand-gated ion channels that
      mediate the influx and efflux of charged ions across the plasma membrane, thereby
      controlling the membrane potential and mediating intracellular signal
      transduction pathways. These channels thus present potential targets for
      experimental modulation of immune responses and for therapeutic interventions in
      immune disease. Small molecule drugs and natural toxins acting on ion channels
      have illustrated the potential therapeutic benefit of targeting ion channels on
      immune cells. Unwanted side effects and immunogenicity have however hampered the
      application of these molecules. Owing to their high specificity, low
      immunogenicity and beneficial pharmacodynamics, antibodies targeting membrane and
      secretory proteins have emerged as potent therapeutics in oncology and
      inflammation. Nanobodies-single domain fragments derived from heavy chain
      antibodies naturally occurring in camelids-offer additional benefits versus
      antibodies, including protrusion into cryptic epitopes and easy formatting of
      multi-specific reagents. Here we review recent progress in the development and
      application of antibodies and Nanobodies targeting ion channels on immune cells.

PMID- 29579625
TI  - Course of bipolar illness worsens after onset of insulin resistance.
AB  - Cross-sectional studies indicate that comorbid insulin resistance (IR) and type 2
      diabetes are associated with a more severe course of bipolar disorder (BD);
      however, this relationship has not previously been assessed longitudinally. To
      address this, we reviewed health records of a case series of six patients with BD
      and comorbid IR. Severity and length of affective episodes (both mania and
      depression) over the lifetime were recorded using the Affective Morbidity Index;
      these data were obtained from ongoing prospective follow-up and from detailed
      retrospective chart reviews. All six patients with a previously episodic,
      relapsing-remitting course of illness experienced a worsening of morbidity after
      the onset of laboratory-demonstrated IR. These results suggest that IR may be a
      potential testable, modifiable factor in the progression of BD from a treatment
      responsive (episodic) to a non-responsive (chronic) course of illness.

PMID- 29579626
TI  - Applications of genetically engineered human pluripotent stem cell reporters in
      cardiac stem cell biology.
AB  - The advent of human pluripotent stem cells (hPSCs) has benefited many fields,
      from regenerative medicine to disease modeling, with an especially profound
      effect in cardiac research. Coupled with other novel technologies in genome
      engineering, hPSCs offer a great opportunity to delineate human cardiac lineages,
      investigate inherited cardiovascular diseases, and assess the safety and efficacy
      of cell-based therapies. In this review, we provide an overview of methods for
      generating genetically engineered hPSC reporters and a succinct synopsis of a
      variety of hPSC reporters, with a particular focus on their applications in
      cardiac stem cell biology.

PMID- 29579628
TI  - A brief history of NEDA.

PMID- 29579627
TI  - Lenalidomide plus dexamethasone for patients with relapsed or refractory multiple
      myeloma: Final results of a non-interventional study and comparison with the
      pivotal phase 3 clinical trials.
AB  - Lenalidomide (LEN) is an immunomodulatory drug with significant clinical activity
      against relapsed and refractory multiple myeloma (r/r MM). Based on the pivotal
      phase 3 trials MM-009 and MM-010, LEN in combination with dexamethasone (DEX) is
      approved for treatment of patients with MM who have received at least one prior
      therapy. LEN monotherapy is also approved in first line treatment. Here, we
      evaluated LEN/DEX combination therapy in a non-interventional study in patients
      with r/r MM in routine clinical practice. Patients received LEN/DEX as per
      Summary of Product Characteristics. Ninety-eight patients were treated with at
      least 1 cycle of LEN/DEX (median age 71 years; range, 42-88), forty-eight
      patients with at least 6 cycles. The Kaplan-Meier estimate for overall median
      time to progression was 12.0 months, 13.9 months for patients receiving second
      line therapy and 10.3 months for third-line or higher-line therapy. The overall
      response rate was 60.2%. The median overall survival was 24.3 months. The most
      common adverse events were anemia (32.7%), thrombocytopenia (27.6%) and
      leukopenia (24.5%). Seven (7.1%) patients developed thromboembolic events despite
      prophylaxis. In conclusion, the combination of LEN/DEX administered to patients
      with r/r MM in routine clinical practice showed similar effectiveness and safety
      as demonstrated in the registration trials.

PMID- 29579629
TI  - The evolution of "No Evidence of Disease Activity" in multiple sclerosis.
AB  - The availability of effective therapies for patients with relapsing-remitting
      multiple sclerosis (RRMS) has prompted a re-evaluation of the most appropriate
      way to measure treatment response, both in clinical trials and clinical practice.
      Traditional parameters of treatment efficacy such as annualized relapse rate,
      magnetic resonance imaging (MRI) activity, and disability progression have an
      important place, but their relative merit is uncertain, and the role of other
      factors such as brain atrophy is still under study. More recently, composite
      measures such as "no evidence of disease activity" (NEDA) have emerged as new
      potential treatment targets, but NEDA itself has variable definitions, is not
      well validated, and may be hard to implement as a treatment goal in a clinical
      setting. We describe the development of NEDA as an outcome measure in MS, discuss
      definitions including NEDA-3 and NEDA-4, and review the strengths and limitations
      of NEDA, indicating where further research is needed.

PMID- 29579630
TI  - Editors' Welcome.

PMID- 29579631
TI  - Are the high-costs of MS disease-modifying therapies justified?

PMID- 29579632
TI  - Maternal exercise increases but concurrent maternal fluoxetine prevents the
      increase in hippocampal neurogenesis of adult offspring.
AB  - Treating postpartum depression (PPD) with pharmacological antidepressants like
      fluoxetine (FLX) is complicated because these drugs can remain active in breast
      milk and potentially affect infant development. Alternatively, non
      pharmacological treatments such as exercise are associated with beneficial
      effects on infant development but its potential ability to counter the effects of
      PPD are largely unknown. To investigate this, we treated dams with corticosterone
      (CORT) or vehicle (sesame oil) from postpartum days 2-25 to model PPD. Within oil
      and CORT treatments, dams were also assigned to one of these treatments: 1)
      exercise (voluntary running wheel) + FLX (10 mg/kg, i.p.), 2) exercise + saline
      (vehicle for FLX), 3) no exercise + FLX, 4) no exercise + saline. Both male and
      female offspring were analyzed, and this generated a total of 16 experimental
      groups for this study. Adult male and female offspring (125 d old) of these dams
      were tested for anxiety-like behavior in the novelty suppressed feeding test and
      stress reactivity in the dexamethasone suppression test. Hippocampal tissue was
      processed for doublecortin, a protein expressed in immature neurons. Regardless
      of sex, maternal exercise increased neurogenesis in the dorsal hippocampus of
      adult offspring, but concurrent exposure to maternal fluoxetine prevented this
      effect. Exposure to either maternal exercise or maternal FLX facilitated HPA
      negative feedback in adult males but not females. Maternal postpartum CORT also
      facilitated HPA feedback in adult offspring of both sexes. Collectively, these
      data indicate that maternal exercise increased dorsal hippocampal neurogenesis in
      both sexes but differentially affected offspring HPA axis based on sex.
      Alternatively, maternal postpartum FLX facilitated HPA axis negative feedback
      only in males. These findings indicate that different types of maternal
      interventions bear long-term effects on offspring outcome with implications for
      treating PPD.

PMID- 29579633
TI  - LC-MS/MS method for the simultaneous analysis of seven antimalarials and two
      active metabolites in dried blood spots for applications in field trials:
      Analytical and clinical validation.
AB  - In epidemiological studies, antimalarials measurements in blood represent the
      best available marker of drugs exposure at population level, an important driver
      for the emergence of drug resistance. We have developed a liquid chromatography
      tandem mass spectrometry method (LC-MS/MS) for the simultaneous quantification of
      7 frequently used antimalarials (amodiaquine, chloroquine, quinine, sulfadoxine,
      pyrimethamine, mefloquine, lumefantrine) and 2 active metabolites (N-desethyl
      amodiaquine, desbutyl-lumefantrine) in 10-MUl dried blood spots (DBS). This
      sampling approach is suitable for field studies wherein blood samples processing,
      transportation and storage are problematic. Sample preparation included
      extraction from a 3 mm-disk punched out of the DBS with 100-MUl of methanol + 1%
      formic acid containing deuterated internal standards for all drugs. Good
      performances were achieved in terms of trueness (-12.1 to +11.1%), precision (1.4
      15.0%) and sensitivity, with lower limits of quantification comprised between 2
      ng/ml (sulfadoxine) and 20 ng/ml (chloroquine, quinine, pyrimethamine,
      mefloquine, lumefantrine and desbutyl-lumefantrine). All analytes were stable in
      DBS kept for 24 h at room temperature and at 37  degrees C. The developed assay
      was applied within the frame of a pharmacokinetic study including 16 healthy
      volunteers who received a single dose of artemether-lumefantrine. Lumefantrine
      concentrations in plasma and in DBS were highly correlated (R = 0.97) at all time
      points, confirming the assumption that lumefantrine concentrations determined in
      DBS confidently reflect blood concentrations. The blood/plasma ratio of 0.56
      obtained using the Bland-Altman approach (and corresponding to the slope of the
      linear regression) is in line with very low penetration of lumefantrine into red
      blood cells. This sensitive multiplex LC-MS/MS assay enabling the simultaneous
      analysis of antimalarials in DBS is suitable for epidemiological studies in field
      conditions.

PMID- 29579634
TI  - Separation and characterization of allergenic polymerized impurities from
      cephalosporin for injection by trap free two-dimensional high performance size
      exclusion chromatography * reversed phase liquid chromatography coupled with ion
      trap time-of-flight mass spectrometry.
AB  - As requested by regulatory authorities, polymerized impurities are an important
      issue of quality control. In this study, we presented the utilization of a trap
      free two-dimensional chromatography, which was consisted by a high performance
      size exclusion chromatography (HPSEC) and a reversed-phase liquid chromatography
      (RP-LC) coupled to ion trap time-of-flight mass spectrometry with positive mode
      of electrospray ionization, to separate and characterize ten allergenic
      impurities in ceftazidime for injection, cefazolin sodium for injection,
      cefoperazone sodium and sulbactam sodium for injection and cefamandole nafate for
      injection. An effective method for characterizing the polymerized impurities in
      beta-lactam antibiotics was established on the basis of column-switching
      technique which effectively combined the advantages of HPSEC and the ability of
      RP-HPLC to identify the special impurities. In the first dimension, the column
      was the Xtimate SEC-120 analytical column (7.8 mm * 30 cm, 5 MUm) and the flow
      rate was 1.0 mL min-1 with gradient elution using 0.005 mol L-1 phosphate buffer
      solution at pH 7.0 and acetonitrile as mobile phase. In the second dimension, the
      analytical column was ZORBAX SB-C18 (4.6 * 150 mm, 3.5 MUm) using ammonium
      formate solution (10 mM) and ammonium formate (8 mM) in [acetonitrile-water (4:1,
      v/v)] solution as mobile phase at a flow rate of 0.4 mL min-1. Eluent associate
      with each peak separated in the first dimension was trapped by a 20 MUL
      quantitative loop and then transferred (via a six-port valve) into the second
      dimension system with volatile mobile phase. Through the multiple heart-cutting
      2D-LC approach and online desalting technique, the problem of incompatibility
      between non-volatile mobile phase and mass spectrometry was solved completely.
      The fragmentation behaviors of ten allergenic impurities were studied. The
      structures of ten allergenic impurities in cephalosporin drug substance were
      deduced based on the HPLC-MSn data, in which four impurities were polymerized
      impurities. The forming factors of polymerized impurity in cephalosporins were
      also studied.

PMID- 29579635
TI  - Silylation of acetaminophen by trifluoroacetamide-based silylation agents.
AB  - In the presented report, we have described the silylation reaction between the
      amide group in acetaminophen and a two most popular trifluoroacetamide-based
      silylation reagents - BSTFA and MSTFA. Both reagents had a amide groups on
      structures. An investigation was made through the performance of a set of
      experiments, GC-MS analysis, and a theoretical study, namely interpretation of
      mass spectra, presentation of the resonance states of all the involved compounds
      and SN2 reaction schemes, which was found to be different when BSTFA and MSTFA
      was applied. The negligible effect of used solvent was also described. The
      fragmentation of TMS-derivatives (MS spectra) was presented and it has confirmed
      our previous investigations with silylation of pharmaceuticals, and a general
      rules of fragmentation patterns. Thanks to this the structure of di-O,O-TMS
      acetaminophen was proven.

PMID- 29579636
TI  - Determination of dexmedetomidine by UHPLC-MS/MS and its application to evaluate
      the effect of dexmedetomidine concentration on the target-controlled infusion
      concentration of propofol.
AB  - The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used
      in the field of anaesthesiology. This study aimed to develop and validate a
      rapid, simple and sensitive ultra high-performance liquid chromatography-tandem
      mass spectrometry (UHPLC-MS/MS) method for the determination of DEX in human
      plasma. The method was applied to evaluate the effect of DEX concentration on the
      target-controlled infusion (TCI) concentration of PPF. Analytes were separated on
      a Waters XTERRA(r) MS C18 column with a mobile phase of acetonitrile-methanol
      water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v) at
      a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive
      selection reaction monitoring mode. The 201.12 -> 95.12 and 515.29 -> 275.68 mass
      transitions of DEX and IS (telmisartan), respectively, were monitored. The
      calibration curve of DEX was linear over the concentrations of 0.1-10 ng/mL. The
      intra-batch and inter-batch precisions of quality control samples were less than
      10.05% and had accuracies of less than 6.25%. The newly developed method was
      successfully applied to quantify the DEX concentrations of plasma samples from 34
      patients who were co-medicated with DEX prior to receiving anaesthesia by PPF.
      Results showed that comedication with DEX could reduce the requirements of PPF.
      Specifically, it was firstly found that the concentration of DEX is negatively
      correlated with the TCI concentration of PPF at the time of loss of
      consciousness.

PMID- 29579637
TI  - Interactions between the growth hormone and cytokines - A review.
AB  - Numerous reports on the interactions between the immune and endocrine systems,
      especially growth hormone axis, can be found in the literature. Growth hormone
      acts mainly indirectly through insulin-like growth factor-1, which stimulates the
      growth and development processes, metabolism of lipids, proteins, and
      carbohydrates, and it also has a modulating effect on the cells of the immune
      system. Several studies have been conducted on the influence of growth hormone
      therapy on the immunological parameters in children and adults with and without
      growth hormone deficiency. However, there have been no definite results and some
      of them have been even contradictory. Some studies have suggested that
      administration of growth hormone increases the production of tumor necrosis
      factor and certain pro- and anti-inflammatory cytokines; whereas other studies
      have demonstrated the lack of correlation between growth hormone and
      interleukins. The aim of this paper was to evaluate the available literature on
      the interaction between growth hormone and TNF-alpha, pro-inflammatory (IL-1beta,
      IL-2, IL-6) and anti-inflammatory (IL-4, IL-10) interleukins.

PMID- 29579638
TI  - Association between organohalogenated pollutants in cord blood and thyroid
      function in newborns and mothers from Belgian population.
AB  - The last decades have seen the increasing prevalence of thyroid disorders. These
      augmentations could be the consequence of the increasing contamination of the
      environment by chemicals that may disrupt the thyroid function. Indeed, in vitro
      studies have shown that many chemicals contaminating our environment and
      highlighted in human serum, are able to interfere with the thyroid function.
      Given the crucial importance of thyroid hormones on neurodevelopment in fetus and
      newborns, the influence of these pollutants on newborn thyroid homeostasis is a
      major health concern. Unfortunately, the overall evidence for a deleterious
      influence of environmental pollutants on thyroid remains poorly studied.
      Therefore, we assessed the contamination by polychlorinated biphenyls (PCBs),
      organochlorine pesticides and perfluorinated compounds (PFC) in 221 cord blood
      samples collected in Belgium between 2013 and 2016. Our results showed that
      compared to previous studies performed on newborns recruited in Belgium during
      the two last decades, the present pollutant contamination is declining.
      Multivariate statistical analyses pointed out a decrease of thyroid stimulating
      hormone (TSH) level in male newborns with detectable level of 4,4'-
      dichlorodiphenyldichloroethylene (4,4'-DDE) in comparison with those with no
      detectable level (p = 0.025). We also highlighted a negative association between
      perfluorononanoic acid (PFNA) concentration and TSH in male newborns (p = 0.018).
      Logistic regression showed increased odds ratio for presentation of hypothyroid
      in mother for each one unit augmentation of log natural concentration of PFOA (OR
      = 2.30, [1.18-4.5]) and PFOS (OR = 2.03 [1.08-3.83]). Our findings showed that
      the residual contamination by PFCs and organochlorine pollutants in cord blood
      are correlated with thyroid hormone in the newborns and the risk of hypothyroid
      in mothers.

PMID- 29579639
TI  - Generation of a human induced pluripotent stem cell line (VRFi001-A) from orbital
      adipose tissue of a bilateral retinoblastoma patient with heterozygous RB1 gene
      deletion.
AB  - Retinoblastoma (RB) is a pediatric intraocular tumor caused by mutations in
      retinoblastoma (RB1) gene. We have generated induced pluripotent stem cell line
      VRFi001-A from a bilateral retinoblastoma patient with heterozygous RB1 gene
      deletion. The iPSC line VRFi001-A retained the mutation and expressed
      pluripotency markers, had a normal karyotype and was capable of trilineage
      differentiation.

PMID- 29579640
TI  - Soybean TCP transcription factors: Evolution, classification, protein interaction
      and stress and hormone responsiveness.
AB  - TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, a family of plant
      specific proteins, play crucial roles in plant growth and development and stress
      response. However, systematical information is unknown regarding the TCP gene
      family in soybean. In the present study, a total of 54 GmTCPs were identified in
      soybean, which were grouped into 11 groups with the typical TCP conserved
      domains. Phylogenetic relationship, protein motif and gene structure analyses
      distinguished the GmTCPs into two homology classes: Class I and Class II. Class
      II was then differentiated into two subclasses: CIN and CYC/TB1. Unique cis
      element number and composition existed in the promoter regions which might be
      involved in the gene transcriptional regulation of different GmTCPs. Tissue
      expression analysis demonstrated the diverse spatiotemporal expression profiles
      of GmTCPs. Furthermore, the interaction protein of one previously functionally
      unknown TCP protein-GmTCP8 was investigated. Yeast two-hybrid assay showed the
      interaction between GmTCP8 and an abscisic acid receptor (GmPYL10). QRT-PCR
      assays indicated the distinct expression profiles of GmTCPs in response to
      abiotic stresses (heat, drought and salt) and stress-related signals (abscisic
      acid, brassinolide, salicylicacid and methyl jasmonate). These results will
      facilitate to uncover the possible roles of GmTCPs under abiotic stress and
      hormone signal responses in soybean.

PMID- 29579641
TI  - Expression of heterologous lycopene beta-cyclase gene in flax can cause silencing
      of its endogenous counterpart by changes in gene-body methylation and in ABA
      homeostasis mechanism.
AB  - Previously we described flax plants with expression of Arabidopsis lycopene beta
      cyclase (lcb) gene in which decreased expression of the endogenous lcb and
      increased resistance to fungal pathogen was observed. We suggested that co
      suppression was responsible for the change. In this study we investigated the
      molecular basis of the observed effect in detail. We found that methylation
      changes in the Lulcb gene body might be responsible for repression of the gene.
      Treatment with azacitidine (DNA methylation inhibitor) confirmed the results.
      Moreover, we studied how the manipulation of carotenoid biosynthesis pathway
      increased ABA level in these plants. We suggest that elevated ABA levels may be
      responsible for the increased resistance of the flax plants to pathogen infection
      through activation of chitinase (PR gene).

PMID- 29579642
TI  - Molecular docking studies and facile synthesis of most potent biologically active
      N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4
      yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide hybrids: An approach for
      microwave-assisted syntheses and biological evaluation.
AB  - An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted
      phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6
      dihydropyrimidine-5-carboxamide derivatives (4a-4j) under microwave-irradiation
      has been described. All the newly synthesized compounds (4a-4j) were
      characterized by elemental analysis and spectroscopic studies. The synthesised
      compounds (4a-4j) were evaluated for their antibacterial activity by agar-well
      diffusion method and anti-inflammatory activity by egg albumin denaturation
      method. The compound (4f) exhibits antibacterial effect with MIC-2.5 MUg/mL
      against gram positive S. aureus bacterial strain compared to standard
      ciprofloxacin drug (MIC-10 MUg/mL). The compound (4c) shows an inhibition of heat
      induced protein denaturation 75.42% at a concentration of 31.25 MUg/ml and is
      almost ten times more active than compared to standard aceclofenac drug (5.50%).
      Molecular docking study has been performed for all the synthesized compounds with
      S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite
      promising.

PMID- 29579643
TI  - Corrigendum to "Conditional loss of Spata7 in photoreceptors causes progressive
      retinal degeneration in mice" [Exp. Eye Res. 166 (2018) 120-130].

PMID- 29579644
TI  - Physiotherapeutic interventions in multiple sclerosis across Europe: Regions and
      other factors that matter.
AB  - BACKGROUND: A wide variety of interventions exists in physical therapy (PT), but
      knowledge about their use across different geographical regions is limited. This
      study investigated the use of PT interventions in people with multiple sclerosis
      (MS) across Europe. It aimed to determine whether regions differ in applying
      interventions, and explore whether factors other than regions play a role in
      their use. METHODS: In an online cross-sectional survey, 212 respondents from 115
      European workplaces providing PT services to people with MS representing 26
      countries (four European regions) participated. Cluster analysis, Pearson Chi
      squared test and a Poisson regression model were used to analyze the data.
      RESULTS: Thirteen of 45 listed PT interventions were used by more than 75% of
      centers, while nine interventions were used by less than 25%. For 12
      interventions, regions differed markedly in their use. Cluster analysis of
      centers identified four clusters similar in their intervention use. Cluster
      assignment did not fully align with regions. While center region was important,
      center size, number and gender of physical therapists working in the center, and
      time since qualification also played a role. Cluster analysis exploring the use
      of the interventions provided the basis for a categorization of PT interventions
      in line with their primary focus: 1. Physical activity
      (fitness/endurance/resistance) training; 2. Neuroproprioceptive
      "facilitation/inhibition"; 3. Motor/skill acquisition (individualized therapy
      led); 4. Technology based interventions. CONCLUSIONS: To our knowledge this is
      the first study that has explored this topic in MS. The results broaden our
      understanding of the different PT interventions used in MS, as well as the
      context of their use.

PMID- 29579645
TI  - Rapid detection of single E. coli bacteria using a graphene-based field-effect
      transistor device.
AB  - Contamination of surface and drinking water due to the presence of Escherichia
      coli bacteria is a major cause of water-borne disease outbreak. To address unmet
      challenges for practical pathogen detection in contaminated samples, we report
      fabrication of thermally reduced graphene oxide-based field-effect transistor
      (rGO FET) passivated with an ultrathin layer of Al2O3 for real-time detection of
      E. coli bacteria. The sensor could detect a single E. coli cell within 50 s in a
      1 uL sample volume. The ultrathin layer of Al2O3 acted as a barrier between rGO
      and potential interferents present in the sample. E. coli specific antibodies
      anchored on gold nanoparticles acted as probes for selective capture of E. coli.
      The high density of negative charge on the surface of E. coli cells strongly
      modulates the concentration of majority charge carriers in the rGO monolayer,
      thereby allowing real-time monitoring of E. coli concentration in a given sample.
      With a low detection limit of single cell, the FET sensor had a linear range of 1
      100 CFU in 1 uL volume of sample (i.e., 103 to 105 CFU/ mL). The biosensor with
      good selectivity and rapid detection was further successfully demonstrated for E.
      coli sensing in river water. The rGO-based FET sensor provides a low cost and
      label-free approach, and can be mass produced for detection of a broad spectrum
      of pathogens in water or other liquid media.

PMID- 29579646
TI  - Aptamer-based biosensors and nanosensors for the detection of vascular
      endothelial growth factor (VEGF): A review.
AB  - Vascular endothelial growth factor (VEGF) is a key regulator of vascular
      formation and a predominant protein biomarker in cancer angiogenesis. Owing to
      its crucial roles in the cancer metastasis, VEGF detection and quantification is
      of great importance in clinical diagnostics. Today, there exist a wide variety of
      detection strategies for identifying many types of disease biomarkers, especially
      for VEGF. As artificial single-stranded DNA or RNA oligonucleotides with
      catalytic and receptor properties, aptamers have drawn lots of attention to be
      applied in biosensing platforms due to their target-induced conformational
      changes as well as high stability and target versatility. So far, various
      sensitivity-enhancement techniques in combination with a broad range of smart
      nanomaterials have integrated into the design of novel aptasensors to improve
      detection limit and sensitivity of analyte detection. This review article
      provides a brief classification and description of the research progresses of
      aptamer-based biosensors and nanobiosensors for the detection and quantitative
      determination of VEGF based on optical and electrochemical platforms.

PMID- 29579647
TI  - Monitoring the degradation of physical properties and fire hazards of high-impact
      polystyrene composite with different ageing time in natural environments.
AB  - The current study aims at monitoring the role of the different natural
      environments on the physical properties and fire hazards of HIPS composites
      ageing in Turpan and Qionghai. The results indicated that the chromatic
      aberration and degradation of surface appearance intensified with the increasing
      ageing time. More flame retardants migrated and were eroded for HIPS composites
      ageing in Qionghai than those ageing in Turpan, which was caused by the
      combination of sunlight, high temperature and rainwater in Qionghai. After
      degradation in the natural environments, the HIPS composites possessed the lower
      thermal stability and char residues, more toxic gases release, higher peak heat
      release rate and fire hazard. For example, the peak heat release rate in Qionghai
      increased by 88.9%, which is much higher than that of in Turpan (55.6%).
      Moreover, the tensile strength and elongation at break decreased by 46% and 59%
      for HIPS composites ageing in Turpan and reduced by 53% and 67% for HIPS
      composites aged in Qionghai, respectively. The results demonstrate that more
      serious degradation of physical properties and higher fire hazard for HIPS
      composites ageing in Qionghai than those in Turpan due to the different natural
      ageing environments.

PMID- 29579648
TI  - A representative overview of the genetic diversity and lipooligosaccharide
      sialylation in Campylobacter jejuni along the broiler production chain in France
      and its comparison with human isolates.
AB  - Campylobacter jejuni is the most common cause of bacterial gastroenteritis
      worldwide and is associated with post-infectious neuropathies. Moreover, the
      chicken reservoir is described as the main source of human infection and C.
      jejuni sialylated lipooligosaccharides seem to play an important role in the
      pathogenesis of neuropathies. In this study, MultiLocus Sequence Typing (MLST)
      and Comparative Genomic Fingerprinting using 40 assay genes (CGF40) were used to
      describe C. jejuni populations within clinical isolates and a representative
      collection of isolates from French poultry production. In addition, the
      sialylation of C. jejuni LOS was assessed. Here, we report high levels of genetic
      diversity among both chicken and human disease C. jejuni populations. The
      predominance of the ST-21, ST-45, and ST-464 complexes in chicken isolates and of
      the ST-21, ST-206, and ST-48 complexes in the clinical isolates was observed as
      were correlations between some MLST and CGF40 genotypes. Furthermore, some C.
      jejuni genotypes were frequently isolated among clinical cases as well as all
      along the broiler production chain, suggesting a potentially high implication of
      chicken in human campylobacteriosis in France. Finally, the LOS classes A, B and
      C were predominant within clinical C. jejuni isolates supporting the hypothesis
      of a benefit in infectivity for C. jejuni isolates showing sialylated LOS.

PMID- 29579649
TI  - Nitrogen balances of innovative cropping systems for feedstock production to
      future biorefineries.

PMID- 29579650
TI  - Refractory organic matter in coastal salt marshes-effect on C sequestration
      calculations.
AB  - The age and ability of salt marshes to accumulate and sequester carbon is often
      assessed using the carbon isotopic signatures (Delta14C and delta13C) of
      sedimentary organic matter. However, transfers of allochthonous refractory carbon
      (CRF) from the watershed to marshes would not represent new C sequestration. To
      better understand how refractory carbon (CRF) inputs affect assessments of marsh
      age and C sequestration, Delta14C and delta13C of both total organic carbon
      (TOC), CRF, and non-CRF organic matter fractions were measured in salt marshes
      from four contrasting systems on the North Atlantic coast. To our knowledge, no
      salt marsh sediment study has considered refractory or allochthonous carbon in
      carbon budget calculations or the impact on chronologies. Stable and radiogenic
      isotope data suggest that while TOC was dominated by autochthonous plant inputs,
      CRF was dominated by locally recycled or allochthonous C, the delivery of which
      was controlled by the size and slope of each watershed. Steep-gradient rivers
      analyzed delivered Delta14C-depleted CRF to their estuarine marshes, while the
      site located in the low-gradient river was associated with larger CRF content.
      Finally, the marsh isolated from riverine input contained the least fraction of
      TOC as CRF. Laterally transported CRF caused only a small offset in Delta14C in
      relation to TOC in low-gradient systems (average Delta14C offset was -44.4 and 
      24.20/00 at each location). However, the presence of allochthonous Delta14C
      depleted CRF in sediments of steep-gradient rivers led to large overestimates of
      the time of organic matter deposition (i.e. apparent age was older than the
      'true' time of deposition) (Delta14C offset ranged from -170.6 to -528.90/00).
      Further, reliance on TOC or loss on ignition analyses to calculate C
      sequestration by marshes might produce overestimates of at least as much as 10 to
      20% since neither account for the lateral transport of allochthonous carbon.

PMID- 29579651
TI  - Determination of tylosin excretion from sheep to assess tylosin spread to
      agricultural fields by manure application.
AB  - Antibiotics administered to livestock are partly excreted with urine and feces.
      As livestock excrement is used as manure on agricultural fields, soil may be
      contaminated by excreted antibiotics, potentially resulting in the development of
      antibiotic-resistant bacteria. Therefore, it is necessary to determine the amount
      of antibiotic administered to livestock that could spread to agricultural fields
      through manure application. This study reveals the excretion ratio of tylosin
      from sheep. After developing an analysis procedure for tylosin in urine and feces
      from sheep, a tylosin excretion study was performed with two sheep. Tylosin was
      excreted in urine and feces for four days, after which its concentrations dropped
      below the limits of quantification (urine: 0.5MUg/kg, feces: 2.4MUg/kg). The
      total excretion ratio was 11% on average. The results of our study can provide
      useful knowledge for treating excrement in order to prevent the spread of
      antibiotics to agricultural fields through manure application.

PMID- 29579652
TI  - Analytical approaches for the determination of personal care products and
      evaluation of their occurrence in marine organisms.
AB  - Contamination of the aquatic environment caused by multiple human activities may
      exert a negative impact on all living organisms. Several contaminants of emerging
      concern such as personal care products (PCPs) are continuously released into the
      aquatic environment where they are biologically active and persistent. This work
      reviews the current knowledge, provided by papers published after 2010 and
      indexed by SciFinder, Scopus, and Google search engines, about the determination
      and occurrence of PCPs in marine biota. Analytical methodologies have been
      critically reviewed, emphasizing the importance of green and high-throughput
      approaches and focusing the discussion on the complexity of the solute-matrix
      interaction in the extraction step, as well as the matrix effect in the
      instrumental determination. Finally, the worldwide distribution of PCPs is
      surveyed, taking into account the concentrations found in the same organism in
      different marine environments. Differences among various world areas have been
      highlighted, evidencing some critical aspects from an environmental point of
      view.

PMID- 29579653
TI  - Production of gamma-valerolactone from levulinic acid over a Ru/C catalyst using
      formic acid as the sole hydrogen source.
AB  - Conversion of levulinic acid (LA) to gamma-valerolactone (GVL) over a ruthenium
      carbon (Ru/C) catalyst using formic acid (FA) as the sole hydrogen source in
      cellulose hydrolysis process was investigated. The reaction was accelerated using
      Ru(5wt%)/C as the catalyst and by adding triethylamine. The highest LA conversion
      (87.26%) and GVL yield (80.75%) were obtained using 10g/mol (LA) catalyst and
      150mL/mol (LA) triethylamine at 160 degrees C for 180min. In this reaction, the
      hydrogenation process can only be accomplished in the presence of FA, which is
      the byproduct of LA production from cellulose hydrolysis. The application of this
      new route not only improves the economy of the process, but also avoids the
      energy-costly separation of LA from the LA and FA aqueous mixture. A new reaction
      pathway for the conversion of LA and FA into GVL over Ru/C with triethylamine was
      proposed.

PMID- 29579654
TI  - Increased nutrient concentrations in Lake Erie tributaries influenced by
      greenhouse agriculture.
AB  - Greenhouse production of vegetables is a growing global trade. While greenhouses
      are typically captured under regulations aimed at farmland, they may also
      function as a point source of effluent. In this study, the cumulative impacts
      greenhouse effluents have on riverine macronutrient and trace metal
      concentrations were examined. Water samples were collected Bi-weekly for five
      years from 14 rivers in agriculturally dominated watersheds in southwestern
      Ontario. Nine of the watersheds contained greenhouses with their boundaries.
      Greenhouse influenced rivers had significantly higher concentrations of
      macronutrients (nitrogen, phosphorus, and potassium) and trace metals (copper,
      molybdenum, and zinc). Concentrations within greenhouse influenced rivers
      appeared to decrease over the 5-year study while concentrations within non
      greenhouse influenced river remained constant. The different temporal pattern
      between river types was attributed to increased precipitation during the study
      period. Increases in precipitation diluted concentrations in greenhouse
      influenced rivers; however, non-influenced river runoff proportionally increased
      nutrient mobility and flow, stabilizing the observed concentrations of non-point
      sources. Understanding the dynamic nature of environmental releases of point and
      non-point sources of nutrients and trace metals in mixed agricultural systems
      using riverine water chemistry is complicated by changes in climatic conditions,
      highlighting the need for long-term monitoring of nutrients, river flows and
      weather data in assessing these agricultural sectors.

PMID- 29579655
TI  - Dynamic ecological observations from satellites inform aerobiology of allergenic
      grass pollen.
AB  - Allergic diseases, including respiratory conditions of allergic rhinitis (hay
      fever) and asthma, affect up to 500 million people worldwide. Grass pollen are
      one major source of aeroallergens globally. Pollen forecast methods are generally
      site-based and rely on empirical meteorological relationships and/or the use of
      labour-intensive pollen collection traps that are restricted to sparse sampling
      locations. The spatial and temporal dynamics of the grass pollen sources
      themselves, however, have received less attention. Here we utilised a consistent
      set of MODIS satellite measures of grass cover and seasonal greenness (EVI) over
      five contrasting urban environments, located in Northern (France) and Southern
      Hemispheres (Australia), to evaluate their utility for predicting airborne grass
      pollen concentrations. Strongly seasonal and pronounced pollinating periods,
      synchronous with satellite measures of grass cover greenness, were found at the
      higher latitude temperate sites in France (46-50 degrees  N. Lat.), with peak
      pollen activity lagging peak greenness, on average by 2-3weeks. In contrast, the
      Australian sites (34-38 degrees  S. Lat.) displayed pollinating periods that were
      less synchronous with satellite greenness measures as peak pollen concentrations
      lagged peak greenness by as much as 4 to 7weeks. The Australian sites exhibited
      much higher spatial and inter-annual variations compared to the French sites and
      at the Sydney site, broader and multiple peaks in both pollen concentrations and
      greenness data coincided with flowering of more diverse grasses including
      subtropical species. Utilising generalised additive models (GAMs) we found the
      satellite greenness data of grass cover areas explained 80-90% of airborne grass
      pollen concentrations across the three French sites (p<0.001) and accounted for
      34 to 76% of grass pollen variations over the two sites in Australia (p<0.05).
      Our results demonstrate the potential of satellite sensing to augment forecast
      models of grass pollen aerobiology as a tool to reduce the health and
      socioeconomic burden of pollen-sensitive allergic diseases.

PMID- 29579656
TI  - Temporal and spatial variations in sand and dust storm events in East Asia from
      2007 to 2016: Relationships with surface conditions and climate change.
AB  - We analyzed the frequency and intensity of sand and dust storms (SDSs) in East
      Asia from 2007 to 2016 using observational data from ground stations, numerical
      modeling, and vegetation indices obtained from both satellite and reanalysis
      data. The relationships of SDSs with surface conditions and the synoptic
      circulation pattern were also analyzed. The statistical analyses demonstrated
      that the number and intensity of SDS events recorded in spring during 2007 to
      2016 showed a decreasing trend. The total number of spring SDSs decreased from at
      least ten events per year before 2011 to less than ten events per year after
      2011. The overall average annual variation of the surface dust concentration in
      the main dust source regions decreased 33.24MUg/m3 (-1.75%) annually. The
      variation in the temperatures near and below the ground surface and the amount of
      precipitation and soil moisture all favored an improvement in vegetation
      coverage, which reduced the intensity and frequency of SDSs. The strong winds
      accompanying the influx of cold air from high latitudes showed a decreasing
      trend, leading to a decrease in the number of SDSs and playing a key role in the
      decadal decrease of SDSs. The decrease in the intensity of the polar vortex
      during study period was closely related to the decrease in the intensity and
      frequency of SDSs.

PMID- 29579657
TI  - The effect of selected acidic or alkaline chemical agents amendment on
      leachability of selected heavy metals from sewage sludge.
AB  - The aim of the study was to evaluate the effect of acidic (Fenton's reagent,
      peracetic acid) or alkaline (CaO) chemical agents amendment on chemical forms of
      Pb, Ni, and Cd in sewage sludge. The dose of Fenton's reagent was as follows:
      Fe2+=1g.L-1, Fe2+/H2O2=1:100; stabilisation lasted for 2h. The dose of CaO was
      equal to 1g CaO.gd.m.-1. The dose of CH3COOOH was 2.5g.L-1. Total concentration
      of all metals in the digested sewage sludge was higher than in the soil and it
      did not meet Polish law requirements. Acidic chemical stabilisation of sludge did
      not significantly decrease total metal content in the sludge. Amendment of CaO
      decreased the content of Pb, Cd, and Ni in the sludge. Chemical fractions of
      heavy metals were identified in the sludge (exchangeable, carbonate bound, iron
      oxides bound, organic and residual). The results indicate that stabilisation of
      the sludge with Fenton's reagent and peracetic acid increased the exchangeable
      fraction of Pb, Cd, and Ni compared to the digested sludge, but it did not
      increase shares of mobile forms of metals considered as a total of I-st and II-nd
      fraction. Amendment of CaO increased percent share of examined metals in residual
      fraction. Not-mobile fractions of examined metals overweight the mobile ones in
      all sludge samples regardless of the treatment method.

PMID- 29579658
TI  - Estimating land surface variables and sensitivity analysis for CLM and VIC
      simulations using remote sensing products.
AB  - Assessment of Land Surface Models (LSMs) at heterogeneous terrain and climate
      regimes is essential for understanding complex hydrological and biophysical
      parameterization. This study utilized the two LSMs, Community Land Model (CLM
      4.0) and three layer Variable Infiltration Capacity (VIC-3L), to estimate the
      interaction between land surface and atmosphere by means of energy fluxes
      including net radiation (RN), sensible heat flux (H), latent heat flux (LE), and
      ground heat flux (G). The modeled energy fluxes were analyzed at two sites:
      Freeman Ranch-2 (FR2) located in the lowland region of Texas (272m), and
      Providence 301 (P301) located on the mountains of Sierra Nevada in California
      (2015m) from 2003 to 2013. RN was underestimated by CLM with bias -25.06Wm-2 due
      to its snow hydrology scheme at P301. LE was overestimated by the VIC during
      summer precipitation and had a positive bias of 5.51Wm-2, whereas CLM showed a
      negative bias of -6.58Wm-2 at the FR2 site. G was considered as a residual term
      in CLM, which caused weak performance at P301, while VIC calculated G as a
      function of soil temperature, depth, and hydraulic conductivity. In addition, The
      MOD16 showed similar results with models at FR2; however, at P301, they yielded a
      correlation value of 0.85 and 0.21 for LSMs and MOD16, respectively. The later
      has lower correlation with in situ specifically in summer season caused by
      erroneous biophysical or meteorological inputs to the algorithms. The sensitivity
      analysis between soil moisture and turbulent fluxes, exhibited negative trend
      (especially for LE at P301) due to topography and snow cover. The results from
      this study are conducive to improvements in models and satellite based
      characterization of water and energy fluxes, especially at rugged terrain with
      high elevation, where observational experiments are difficult to conduct.

PMID- 29579659
TI  - Temporal-spatial variability in correlations of drought and flood during recent
      500years in Inner Mongolia, China.
AB  - Drought and flood are two frequent natural disasters in the world. Identification
      of temporal-spatial variability and its scale-dependence for drought-flood
      correlation can help to predict, hence to alleviate the losses. The correlations
      of drought with flood at 1, 3, 5, 10, 50 and 100-year scales at moving window of
      30years during recent 500years were analyzed by spatial statistics based on
      geographical information system in Inner Mongolia, China. The results
      demonstrated that the frequency and intensity of two disasters increased
      generally during last 500years. The drought-flood correlations indicated a rhythm
      of alternate positive and negative relation with unspecific timescale, enlarged
      by prolonging of time scale from 1year to 5years, for either frequency or
      intensity. A lag effect, flood always occurred at the 4 or 5year following
      drought was observed. Located in the climatic marginal zone, eastern study region
      was strongly affected by the East Asia monsoon, showed a weak drought-flood
      correlation; western study region was controlled by continental climate, showed a
      significant drought-flood correlation. These correlations were also affected by
      periodic ENSO disturbance and mountain terrains. With the climatic changes, the
      drought-flood correlations also change in recent decades. These long-range
      correlations at various temporal-spatial scales provide a theoretical basis for
      the scientific prediction of drought and flood outbreaks, for a long term as well
      as a short wavelet.

PMID- 29579660
TI  - Assessing the associations of daily respiratory symptoms and lung function in
      schoolchildren using an Air Quality Index for ozone: Results from the RESPOZE
      panel study in Athens, Greece.
AB  - BACKGROUND: Air Quality indicators or indices (AQIs) are mainly used for
      communicating the air pollution levels and risk to the general population.
      However, very few epidemiological studies have used AQIs for characterizing
      exposure. OBJECTIVE: In the framework of the RESPOZE panel study we evaluated the
      association of daily ozone AQI levels with the daily occurrence of respiratory
      symptoms and Peak Expiratory Flow (PEF) and compared the effects with those
      estimated using measurements from fixed outdoor monitoring sites, in the city of
      Athens, Greece. MATERIALS AND METHODS: A panel of 97 children, aged 10-11years,
      was followed intensively for 35days (5weeks) during the academic year 2013-14.
      PEF and symptoms were recorded daily by each child. Two ozone AQIs classifying
      the air quality into 7 categories of increasing severity, were calculated; one
      characterizing the whole Athens area and one the local area around the child's
      residence and school. Measurements from fixed sites were also used. Mixed effects
      models for repeated measurements were applied, adjusting for several confounders.
      RESULTS: Increasing ozone levels were associated with increased incidence of
      symptoms, but the strongest and most statistically significant associations were
      found with the local air quality characterization with the AQI. Specifically, an
      increase in AQI-local by one category was associated with 34% (95% CI: 9%, 64%)
      increased odds of stuffy nose. When the AQI categories were "Bad" and "Severe",
      an increase in the incidence of cough was observed (OR 3.05 (95% CI: 1.29, 7.22)
      and 6.42 (95% CI: 1.47, 28.03) respectively). We did not observe a statistically
      significant association between AQI and PEF. CONCLUSION: Our results show that
      the use of an AQI based on local conditions may be advantageous over the use of
      only measurements when investigating the effects of air pollution on health
      outcomes for improving communication of risk to the public.

PMID- 29579661
TI  - Microplastic ingestion by Daphnia magna and its enhancement on algal growth.
AB  - The rapid increase in plastic use over the last few decades has resulted in
      plastic pollution in freshwater and marine ecosystems. However, more attention
      has been paid to plastic pollution in marine ecosystems than to freshwater
      ecosystems. This research determined microplastic ingestion by Daphnia magna and
      the potential effect of microplastics on the organism's survival and
      reproduction. The study also examined the potential of microplastics to enhance
      algal growth in support of understanding effects of microplastic ingestion on the
      organism. When exposed to 25, 50, and 100mg/L fluorescent green polyethylene
      microbeads at size of 63-75MUm, D. magna ingested significant amount of plastic
      microbeads. The number of ingested beads increased with increasing particle
      concentration and exposure time. However, no significant effect on survival and
      reproduction was observed although the gut of D. magna was filled with plastic
      microbeads. In the algal experiment, Raphidocelis subcapitata grew more in the
      exposure media with the present of plastic microbeads than without plastic
      microbeads. This result suggests that plastic microbeads could serve as
      substrates for R. subcapitata to grow. Raphidocelis subcapitata then could be
      transferred to the organism's gut and provided energy for survival and
      reproduction. Results of the present study add to the literature of microplastic
      ingestion by aquatic organisms. Caution should be taken when interpreting hazards
      of microplastics based on ingestion, such as the measurement unit and the
      presence of algae in the environment.

PMID- 29579662
TI  - Application of a multivariate analysis method for non-target screening detection
      of persistent transformation products during the cork boiling wastewater
      treatment.
AB  - Cork boiling wastewater is a very complex mixture of naturally occurring
      compounds leached and partially oxidized during the boiling cycles. The effluent
      generated is recalcitrant and could cause a significant environmental impact.
      Moreover, if this untreated industrial wastewater enters a municipal wastewater
      treatment plant it could hamper or reduce the efficiency of most activated sludge
      degradation processes. Despite the efforts to treat the cork boiling wastewater
      for reusing purposes, is still not well-known how safe these compounds (original
      compounds and oxidation by-products) will be. The purpose of this work was to
      apply an HPLC-high resolution mass spectrometry method and subsequent non-target
      screening using a multivariate analysis method (PCA), to explore relationships
      between samples (treatments) and spectral features (masses or compounds) that
      could indicate changes in formation, degradation or polarity, during
      coagulation/flocculation (C/F) and photo-Fenton (PhF). Although, most of the
      signal intensities were reduced after the treatment line, 16 and 4 new peaks were
      detected to be formed after C/F and PhF processes respectively. The use of this
      non-target approach showed to be an effective strategy to explore, classify and
      detect transformation products during the treatment of an unknown complex
      mixture.

PMID- 29579663
TI  - Composition and functional diversity of microbial community across a mangrove
      inhabited mudflat as revealed by 16S rDNA gene sequences.
AB  - The gradient distribution of microbial communities has been detected in profiles
      along many natural environments. In a mangrove seedlings inhabited mudflat, the
      microbes drive a variety of biogeochemical processes and are associated with a
      dramatically changed environment across the tidal zones of mudflat. A better
      understanding of microbial composition, diversity and associated functional
      profiles in relation to physicochemical influences could provide more insights
      into the ecological functions of microbes in a coastal mangrove ecosystem. In
      this study, the variation of microbial community along successive tidal flats
      inhabited by mangrove seedlings were characterized based on the 16S rDNA gene
      sequences, and then the factors that shape the bacterial and archaeal communities
      were determined. Results showed that the tidal cycles strongly influence the
      distribution of bacterial and archaeal communities. Dissimilarity and gradient
      distribution of microbial communities were found among high tidal flat, mid-low
      tidal flat and seawater. Discrepancies were also as well observed from the
      surface to subsurface layers specifically in the high tidal flat. For example,
      Alphaproteobacteria displayed an increasing trend from low tidal to high tidal
      flat and vice versa for Deltaproteobacteria; Cyanobacteria and Thaumarchaeota
      were more dominant in the surface layer than the subsurface. In addition, by
      classifying the microorganisms into metabolic functional groups, we were able to
      identify the biogeochemical pathway that was dominant in each zone. The
      (oxygenic) photoautotrophy and nitrate reduction were enhanced in the mangrove
      inhabited mid tidal flat. It revealed the ability of xenobiotic metabolism
      microbes to degrade, transform, or accumulate environmental hydrocarbon
      pollutants in seawater, increasing sulfur-related respiration from high tidal to
      low tidal flat. An opposite distribution was found for major nitrogen cycling
      processes. The shift of both composition and function of microbial communities
      were significantly related to light, oxygen availability and total dissolved
      nitrogen instead of sediment types or salinity.

PMID- 29579664
TI  - Environmental correlates underlying elevational richness, abundance, and biomass
      patterns of multi-feeding guilds in litter invertebrates across the treeline.
AB  - Elevational richness patterns and underlying environmental correlates have
      contributed greatly to a range of general theories of biodiversity. However, the
      mechanisms underlying elevational abundance and biomass patterns across several
      trophic levels in belowground food webs remain largely unknown. In this study, we
      aimed to disentangle the relationships between the elevational patterns of
      different trophic levels of litter invertebrates and their underlying
      environmental correlates for two contrasting ecosystems separated by the
      treeline. We sampled 119 plots from 1020 to 1770 asl in forest and 21 plots from
      1790 to 2280 asl in meadow on Dongling Mountain, northwest of Beijing, China.
      Four functional guilds were divided based on feeding regime: omnivores,
      herbivores, predators, and detritivores. We used eigenvector-based spatial
      filters to account for spatial autocorrelation and multi-model selection to
      determine the best environmental correlates for the community attributes of the
      different feeding guilds. The results showed that the richness, abundance and
      biomass of omnivores declined with increasing elevation in the meadow, whereas
      there was a hump-shaped richness pattern for detritivores. The richness and
      abundance of different feeding guilds were positively correlated in the forest,
      while not in the meadow. In the forest, the variances of richness in omnivores,
      predators, and detritivores were mostly correlated with litter thickness, with
      omnivores being best explained by mean annual temperature in the meadow. In
      conclusion, hump-shaped elevational richness, abundance and biomass patterns
      driven by the forest gradient below the treeline existed in all feeding guilds of
      litter invertebrates. Climate replaced productivity as the primary factor that
      drove the richness patterns of omnivores above the treeline, whereas
      heterogeneity replaced climate for herbivores. Our results highlight that the
      correlated elevational richness, abundance, and biomass patterns of feeding
      guilds are ecosystem-dependent and that the underlying environmental correlates
      shifted at the treeline for most feeding guilds.

PMID- 29579665
TI  - Microplastics in surface waters of Dongting Lake and Hong Lake, China.
AB  - Microplastics pollution is an environmental issue of increasing concern. Much
      work has been done on the microplastics pollution in the marine environments.
      Although freshwaters are potential sources and transport pathways of plastic
      debris to the oceans, there is a lack of knowledge regarding the presence of
      microplastics in freshwater systems, especially in China, the world's largest
      producer of plastics. This study investigated the occurrence and properties of
      microplastics in surface waters of two important lakes in the middle reaches of
      the Yangtze River. The concentration ranges of microplastics in Dongting Lake and
      Hong Lake were 900-2800 and 1250-4650n/m3, respectively. Fiber was the dominant
      shape. Colored items occupied the majority. Particles with a size of <330MUm
      comprised >20% of total microplastics collected in both lakes. Most of the
      selected particles were identified as plastics, with polyethylene (PE) and
      polypropylene (PP) being the major components. This study can provide valuable
      reference for better understanding the microplastics pollution in inland
      freshwater ecosystems.

PMID- 29579666
TI  - Graphitic carbon nitride based nanocomposites for the photocatalysis of organic
      contaminants under visible irradiation: Progress, limitations and future
      directions.
AB  - Graphitic carbon nitride (g-C3N4) has drawn great attention recently because of
      its visible light response, suitable energy band gap, good redox ability, and
      metal-free nature. g-C3N4 can absorb visible light directly, therefore has better
      photocatalytic ability under solar irradiation and is more energy-efficient than
      TiO2. However, pure g-C3N4 still has the drawbacks of insufficient light
      absorption, small surface area and fast recombination of photogenerated electron
      and hole pairs. This review summarizes the recent progress in the development of
      g-C3N4 nanocomposites to photodegrade organic contaminants in water. Element
      doping especially by potassium has been reported to be an efficient method to
      promote the degradation efficacy. In addition, compound doping improves
      photodegradation performance of g-C3N4, especially Ag3PO4-g-C3N4 which can
      completely degrade 10mgL-1 of methyl orange under visible light irradiation in
      5min, with the rate constant (k) as high as 0.236min-1. Moreover, co-doping
      enhances the photodegradation rate of multiple contaminants while immobilization
      significantly improves catalyst stability. Most of g-C3N4 composites possess high
      reusability enabling their practical applications in wastewater treatment.
      Furthermore, environmental conditions such as solution pH, reaction temperature,
      dissolved oxygen, and dissolved organic matter all have important effects on the
      photocatalytic ability of g-C3N4 photocatalyst. Future work should focus on the
      synthesis of innovative g-C3N4 nanocomposites for the efficient removal of
      organic contaminants in water and wastewater.

PMID- 29579667
TI  - The impact of highway base-saturation flow rate adjustment on Kuwait's transport
      and environmental parameters estimation.
AB  - Traditional transportation systems' management and operation mainly focused on
      improving traffic mobility and safety without imposing any environmental
      concerns. Transportation and environmental issues are interrelated and affected
      by the same parameters especially at signalized intersections. Additionally,
      traffic congestion at signalized intersections has a major contribution in the
      environmental problem as related to vehicle emission, fuel consumption, and
      delay. Therefore, signalized intersections' design and operation is an important
      parameter to minimize the impact on the environment. The design and operation of
      signalized intersections are highly dependent on the base saturation flow rate
      (BSFR). Highway Capacity Manual (HCM) uses a base-saturation flow rate of 1900
      passenger car/h/lane for areas with a population intensity greater than or equal
      to 250,000 and a value of 1750-passenger car/h/lane for less populated areas. The
      base-saturation flow rate value in HCM is derived from a field data collected in
      developed countries. The adopted value in Kuwait is 1800passengercar/h/lane,
      which is the value that used in this analysis as a basis for comparison. Due to
      the difference in behavior between drivers in developed countries and their
      fellows in Kuwait, an adjustment was made to the base-saturation flow rate to
      represent Kuwait's traffic and environmental conditions. The reduction in fuel
      consumption and vehicles' emission after modifying the base-saturation flow rate
      (BSFR increased by 12.45%) was about 34% on average. Direct field measurements of
      the saturation flow rate were used while using the air quality mobile lab to
      calculate emissions' rates.

PMID- 29579668
TI  - Spatially distributed potential evapotranspiration modeling and climate
      projections.
AB  - Evapotranspiration integrates energy and mass transfer between the Earth's
      surface and atmosphere and is the most active mechanism linking the atmosphere,
      hydrosphsophere, lithosphere and biosphere. This study focuses on the fine
      resolution modeling and projection of spatially distributed potential
      evapotranspiration on the large catchment scale as response to climate change.
      Six potential evapotranspiration designed algorithms, systematically selected
      based on a structured criteria and data availability, have been applied and then
      validated to long-term mean monthly data for the Shannon River catchment with a
      50m2 cell size. The best validated algorithm was therefore applied to evaluate
      the possible effect of future climate change on potential evapotranspiration
      rates. Spatially distributed potential evapotranspiration projections have been
      modeled based on climate change projections from multi-GCM ensembles for three
      future time intervals (2020, 2050 and 2080) using a range of different
      Representative Concentration Pathways producing four scenarios for each time
      interval. Finally, seasonal results have been compared to baseline results to
      evaluate the impact of climate change on the potential evapotranspiration and
      therefor on the catchment dynamical water balance. The results present evidence
      that the modeled climate change scenarios would have a significant impact on the
      future potential evapotranspiration rates. All the simulated scenarios predicted
      an increase in potential evapotranspiration for each modeled future time
      interval, which would significantly affect the dynamical catchment water balance.
      This study addresses the gap in the literature of using GIS-based algorithms to
      model fine-scale spatially distributed potential evapotranspiration on the large
      catchment systems based on climatological observations and simulations in
      different climatological zones. Providing fine-scale potential evapotranspiration
      data is very crucial to assess the dynamical catchment water balance to setup
      management scenarios for the water abstractions. This study illustrates a
      transferable systematic method to design GIS-based algorithms to simulate
      spatially distributed potential evapotranspiration on the large catchment
      systems.

PMID- 29579669
TI  - Contamination and health risk assessment of PAHs in farmland soils of the Yinma
      River Basin, China.
AB  - The concentration, composition, sources and incremental lifetime cancer risk of
      farmland soil polycyclic aromatic hydrocarbons (PAHs) of the Yinma River Basin
      were analyzed. In 2016, the total concentration of 16 PAHs ranged from 491.65 to
      1007.73 ng/g in May, from 427.31 to 781.38 ng/g in August and from 580.40 to
      999.40 ng/g in November, respectively. Levels of seven potentially carcinogenic
      PAHs generally accounted for 33-36.7% of total 16 PAHs in three seasons, and the
      PAHs contained two to six rings, mainly Fla, Pyr, and Chr. The correlation
      analysis suggested that the soil organic matter (SOM) was no correlation with
      PAHs except for August, and there were no significant relationship between the pH
      and total PAHs. Isomer ratios indicated that the soil PAHs in the farmland of the
      Yinma River Basin was determined to be the combustion of coal, biomass, and
      petroleum. The toxic equivalent (BaPeq) concentrations ranged from 15.2 to 133 ng
      BaPeq g-1 in three seasons. The 95th percentiles of incremental lifetime cancer
      risk (ILCR) due to human exposure to farmland soil PAHs of the Yinma River Basin
      was (1.36 * 10-6) in May, (1.00 * 10-6) in August, and (1.18 * 10-6) in November
      for children, (1.10 * 10-6) in May, (8.15 * 10-7) in August, and (9.58 * 10-7) in
      November for adolescence and (1.61 * 10-6) in May, (4.22 * 10-6) in August and
      (1.40 * 10-6) in November for adulthood. The result indicated a moderate
      carcinogenic risk and the risk of exposure to farmland soil PAHs was pervasive
      for residents. This investigation might provide useful information on human
      exposure to PAHs in soil of the Yinma River Basin, and is valuable for policy
      makers and scientists.

PMID- 29579670
TI  - Fluoride contamination in groundwater sources in Southwestern Nigeria: Assessment
      using multivariate statistical approach and human health risk.
AB  - The present study investigated the ionic and fluoride concentrations in tap water
      and its associated health risk to local dwellers of Ogun State (Abeokuta south),
      Nigeria. 63 samples were collected from twenty-one different locations. Results
      obtained revealed the mean concentration of fluoride (F-) as 1.23 mg/L. Other
      water quality parameters such as total dissolved solids (TDS), electrical
      conductivity (EC), F-, Fe2+, and SO42- surpassed the WHO guidance for drinking
      water. Strong positive correlation was observed between F- and TDS; F- and pH;
      TDS and EC; TDS and Mg2+; TDS and SO42-; TDS and HCO3-; EC and HCO3-; EC and SO42
      ; Na+ and Cl-; SO42- and Cl-. In addition, Empirical Bayesian Kriging (EBK) model
      was employed to spatially distribute the concentration of the analyzed elements
      within the study region. The chronic daily dose (CDD) and hazard quotient (HQ)
      were also used to evaluate the health risk associated with F-, considering dermal
      and ingestion as pathways. The results revealed that the associated HQ for
      infants between the age range of 6-12months within about 91% of the study region
      surpassed the accepted HQ limit. However, the HQ for age categories 11-16years;
      >65years; 18-21years; 21years; 16-18years within 95.2%, 90.5%, 80.95% and 100% of
      the study location were less than 1. Conclusively, the HQ values obtained in this
      study should serve as a baseline information for water management authorities,
      policymakers and the society at large towards addressing these pollution issues.

PMID- 29579671
TI  - External validation of the TIMI risk score for secondary cardiovascular events
      among patients with recent myocardial infarction.
AB  - BACKGROUND AND AIMS: Risk stratification of patients with recent myocardial
      infarction (MI) for subsequent cardiovascular (CV) events helps identify patients
      most likely to benefit from secondary prevention therapies. This study externally
      validated a new risk score (TRS2P) for secondary events derived from the TRA2
      degrees P-TIMI 50 trial among post-MI patients from two large health care
      systems. METHODS: This retrospective cohort study included 9618 patients treated
      for acute MI at either the Cleveland Clinic (CC) or Geisinger Health System (GHS)
      between 2008 and 2013. Patients with a clinic visit within 2-52 weeks of MI were
      included and followed for CV death, repeat MI, and ischemic stroke through
      electronic medical records (EMR). The TRS2P is based on nine factors determined
      through EMR documentation. Discrimination and calibration of the TRS2P were
      quantified in both patient populations. RESULTS: MI patients at CC and GHS were
      older, had more comorbidities, received fewer medications, and had higher 3-year
      event rates compared to subjects in the TRA2 degrees P trial: 31% (CC), 33%
      (GHS), and 10% (TRA2 degrees P-TIMI 50). The proposed risk score had similar
      discrimination across the three cohorts with c-statistics of 0.66 (CC), 0.66
      (GHS), and 0.67 (TRA2 degrees P-TIMI 50). A strong graded relationship between
      the risk score and event rates was observed in all cohorts, though 3-year event
      rates were consistently higher within TRS2 degrees P strata in the CC and GHS
      cohorts relative to TRA2P-TIMI 50. CONCLUSIONS: The TRS2P demonstrated consistent
      risk discrimination across trial and non-trial patients with recent MI, but event
      rates were consistently higher in the non-trial cohorts.

PMID- 29579672
TI  - Induction of extracranial arteriogenesis by an arteriovenous fistula in a pig
      model.
AB  - BACKGROUND AND AIMS: Arteriogenesis, the positive outward remodeling and growth
      of pre-existent collateral vessels, holds potential as a novel treatment for
      ischemic vascular disease. An extracranial arteriogenesis model in a pig will
      allow us to study molecular changes in a complex arteriolar network in a more
      clinically relevant large-animal model. To increase fluid shear stress in the
      brain, an experimental carotid arteriovenous fistula (AVF model) in minipigs was
      established, providing high flow through the extracranial rete mirabile. The aim
      of the study was to examine whether creation of a carotid AVF can induce
      extracranial arteriogenesis in the pig. METHODS: Angiography was performed to
      demonstrate blood flow diversion. Animals were sacrificed after 0, 3 and 14 days
      post-surgery and both retia mirabilia were removed. Immunohistochemical analysis
      was performed to analyze cell proliferation and accumulation of mononuclear cells
      in the vessel wall. RESULTS: After 3 days of high-flow conditions, increases in
      vascular cell proliferation (approximately 1.5-fold; p = 0.143) and monocyte
      invasion (approximately 6-fold; p = 0.057) were observed when compared to animals
      sacrificed immediately after AVF formation. Quantitative PCR (RT-qPCR) analysis
      from rete mirabile tissue samples 3 days post-surgery revealed that monocyte
      chemoattractant protein (MCP)-1 and tissue inhibitor of metalloproteinases (TIMP)
      1 were highly upregulated. Expression of the pro-arteriogenic marker, CD44,
      reached maximum expression level 14 days post-surgery. CONCLUSIONS: In response
      to high levels of shear stress produced in the pig AVF model, the onset of the
      arteriogenic process can be induced. This was demonstrated by enhanced cell
      proliferation, monocyte invasion and vascular remodeling.

PMID- 29579673
TI  - Associations between normal range albuminuria, renal function and cardiovascular
      function in a population-based imaging study.
AB  - BACKGROUND AND AIMS: In patients with impaired renal function and
      macroalbuminuria, cardiovascular risk factors are highly prevalent, however,
      whether this is also present in the general population is unclear. We
      investigated whether normal-range albuminuria and renal function are associated
      with cardiovascular function in the general population. METHODS: In this cross
      sectional analysis of the NEO study, urinary albumin-creatinine ratio (UACR),
      estimated glomerular filtration rate (eGFR), and intima-media thickness were
      assessed in all participants (n = 6503), and a random subset underwent MRI for
      pulse wave velocity (n = 2451) and/or cardiac imaging (n = 1138). RESULTS:
      Multiple linear regression analysis was performed while adjusting for sex, age,
      smoking, mean arterial blood pressure, total body fat, and fasting glucose. After
      adjustment, albuminuria and renal function were positively associated with left
      ventricle (LV) mass index (UACR, 0.941 g/m2 [95% CI: 0.21,1.67] p = 0.012; eGFR,
      0.748 g/m2 [95% CI: 0.15,1.35] p = 0.015) and LV cardiac index (UACR, 0.056
      L/min/m2 [95% CI: 0.00,0.11] p = 0.038; eGFR, 0.080 L/min/m2 [95% CI: 0.03,0.13]
      p = 0.001). Albuminuria showed a weak association with arterial thickness (UACR,
      0.003 mm [95% CI: 0.00,0.01] p = 0.015) and arterial stiffness (UACR, 0.073 m/s
      [95% CI: 0.01,0.13] p = 0.036), but not with renal function. No associations were
      observed for LV ejection fraction and LV diastolic function. CONCLUSIONS: Normal
      range albuminuria was positively associated with LV mass index, LV cardiac index,
      arterial thickness and arterial stiffness. Our findings support the hypothesis
      that even within normal range, albuminuria is a marker of cardiovascular health.

PMID- 29579674
TI  - Bioremediation of a pentacyclic PAH, Dibenz(a,h)Anthracene- A long road to trip
      with bacteria, fungi, autotrophic eukaryotes and surprises.
AB  - Dibenz(a,h)Anthracene (DBahA), classified as a probable human carcinogen (B2) is
      the first Poly Aromatic Hydrocarbons (PAH) to be chemically purified and used for
      cancer-based studies. Till date, only 30 papers focus on the bioremediation
      aspects of DBahA out of more than 200 research publications for each of the other
      15 priority PAHs. Thus, the review raises an alarm and calls for efficient
      bioremediation strategies for considerable elimination of this compound from the
      environment. This article reviews and segregates the available papers on DBahA
      bioremoval from the beginning till date into bacteria, fungi and plant-mediated
      remediation and offers suggestions for the most competent and cost-effective
      modes to bioremove DBahA from the environment. One of the proficient ways to get
      rid of this PAH could with the use of biosurfactant-enriched bacterial consortium
      in DBahA polluted environment, which is given considerable importance here. Among
      the bacterial and fungal microbiomes, unquestionably the former are the
      beneficiaries which utilize the breakdown products of this PAH metabolized by the
      latter. Nevertheless, the use of plant communities for efficient DBahA
      utilization through fibrous root system is also discussed at length. The current
      status of DBahA as reflected by the publications at https://www.ncbi.nlm.nih.gov
      and recommendations among the explored groups [bacterial/fungal/plant
      communities] for better DBahA elimination are pointed out. Finally, the review
      emphasizes the pros and cons of all the methodologies used for
      selective/combinatorial removal of DBahA and present the domain to the
      researchers to carry forward by incorporating their individual ideas.

PMID- 29579675
TI  - Removal of lindane wastes by advanced electrochemical oxidation.
AB  - The effective removal of recalcitrant organochlorine pesticides including
      hexachlorocyclohexane (HCH) present in a real groundwater coming from a landfill
      of an old lindane (gamma-HCH) factory was performed by electrochemical oxidation
      using a BDD anode and a carbon felt cathode. Groundwater (SigmaHCHs = 0.42 mg L
      1, TOC0 = 9 mg L-1, pH0 = 7, conductivity = 3.7 mS cm-1) was treated as received,
      achieving the complete depletion of the HCH isomers and a mineralization degree
      of 90% at 4 h electrolysis at constant current of 400 mA. Initial groundwater
      contains high chloride concentration (Cl0- = 630 mg L-1) that is progressively
      decreased due to its oxidation to different oxychlorine species: Cl2, HClO, ClO-,
      ClO2- ClO3- and ClO4- some of them (Cl2, HClO, ClO-) playing an important role in
      the oxidation of organic pollutants. The oxidation rate of chloride (and its
      oxidized intermediates) depends on the applied current value. Although some of
      the species generated from them are active oxidants, the presence of inorganic
      salts is detrimental to the efficiency of the electrochemical process when
      working at current densities above 100 mA due to the high consumption of hydroxyl
      radicals in wasting reactions. The initial organic carbon content is not crucial
      for the extension of the process but high organic loads are more profitable for
      cost effectiveness. The addition of a supporting electrolyte to the solution
      could be interesting since it increases the conductivity, reducing the cell
      potential and therefore, decreasing the energy consumption.

PMID- 29579676
TI  - Ciprofloxacin vs. temperature: Antibiotic toxicity in the free-floating liverwort
      Ricciocarpus natans from a climate change perspective.
AB  - The physiological responses of the aquatic liverwort Ricciocarpus natans to
      ciprofloxacin (Cipro) exposure under different growth temperatures were
      investigated. Cipro appears to act as an inhibitor of mitochondrial Complex III
      by blocking the oxidation of quinol, resulting in the formation of hydrogen
      peroxide (H2O2). H2O2 accumulation upon Cipro exposure is responsible for
      decreased photosynthesis in plants. The amount of H2O2 in plants is kept under
      control by antioxidant enzymes, whose activities are central to the responses of
      plants to Cipro yet are influenced by temperature. Increased temperature favored
      Cipro uptake by plants as well as its deleterious effects on mitochondrial
      activity; however, it also favored the activity of antioxidant enzymes, thereby
      preventing the exacerbation of the deleterious effects of Cipro. The uptake of
      Cipro by plants appears to be largely a passive process, although some uptake
      must be driven by an energy-consuming process. Ricciocarpus natans should be
      considered for programs aimed at the reclamation of Cipro since this plant
      exhibits high Cipro-tolerance, the capacity for accumulation and increased uptake
      rates of the antibiotic with increasing temperatures (from 20 to 30  degrees C).

PMID- 29579677
TI  - Humic substances, their microbial interactions and effects on biological
      transformations of organic pollutants in water and soil: A review.
AB  - Depicted as large polymers by the traditional model, humic substances (HS) tend
      to be considered resistant to biodegradation. However, HS should be regarded as
      supramolecular associations of rather small molecules. There is evidence that
      they can be degraded not only by aerobic but also by anaerobic bacteria. HS
      presence alters biological transformations of organic pollutants in water and
      soil. HS, including humin, have a great potential for an application in aerobic
      and anaerobic wastewater treatment as well as in bioremediation. Black carbon
      materials, including char (biochar) and activated carbon (AC), long recognized
      effective sorbents, have been recently discovered to act as effective redox
      mediators (RM), which may significantly accelerate degradation of organic
      pollutants in a way similar to HS. Humic-like coating on the biochar surface has
      been identified. Explanation of mechanisms and possibility of applications of
      black carbon materials have only started to be explored. Results of many original
      and review papers, presented and discussed in this article, show an enormous
      potential for an interesting, multidisciplinary research as well as for a
      development of new, green technologies for biological wastewater treatment and
      bioremediation. Future research areas have been suggested.

PMID- 29579678
TI  - Organohalogen contaminants in common loons (Gavia immer) breeding in Western
      Alberta, Canada.
AB  - We examined the influence of biological and geographical factors on the levels
      and patterns of organohalogen contaminants in blood of adult common loons (Gavia
      immer) collected from 20 lakes in Alberta, Canada. The loons were captured in the
      2006 and 2007 breeding seasons over a 900 m elevation gradient across the eastern
      slope of the Canadian Rocky Mountains. While PCBs dominated the composition of
      these contaminants in loons at all sites (?PCBs > p,p'-DDE > ?PBDEs > ?Chlordanes
      > HCB), p,p'-DDE and ?PBDEs were also important, averaging approximately 50% and
      20% of total PCB concentrations, respectively. ?PCBs and ?PBDEs were higher in
      males than in females. Inter-lake variation was apparent for contaminant
      concentrations and patterns and were largely explained by dietary signatures
      (delta15N and delta13C) and proximity to a large hydroelectric dam. Mean ?PCB
      (19.6 ng/g wet weight (ww)) and organochlorine pesticide (OCP) (p,p'-DDE: 11.8
      ng/g, cis-nonachlor: 0.10 ng/g, trans-nonachlor: 0.32 ng/g, HCB: 0.34 ng/g ww)
      concentrations in loons were approximately 4- to 17-fold lower than average
      concentrations reported in common loons from Atlantic Canada and were well below
      concentrations which have been associated with impaired reproductive success and
      eggshell thinning in other piscivorous birds. Dominant PBDE congeners were BDE47,
      BDE99, and BDE100. The regional mean for ?PBDEs (4.04 ng/g ww) in loons from the
      present study was within the range reported for ?PBDEs in nestling bald eagle
      plasma from British Columbia. This is the first report of PBDEs in loons and the
      first report of PCBs and OCPs in common loons from Western North America.

PMID- 29579679
TI  - Hg in snow cover and snowmelt waters in high-sulfide tailing regions (Ursk
      tailing dump site, Kemerovo region, Russia).
AB  - Gold-bearing polymetallic Cu-Zn deposits of sulphur-pyrite ores were discovered
      in the Novo-Ursk region in the 1930s. The average content of mercury (Hg) was
      approximately 120 MUg/g at the time. A comprehensive study of Hg distribution in
      waste of metal ore enrichment industry was carried out in the cold season on the
      tailing dump site and in adjacent areas. Mercury concentration in among snow
      particulate, dissolved and colloid fractions was determined. The maximal Hg
      content in particulate fraction from the waste tailing site ranged 230-573 MUg/g.
      Such indices as the frequency of aerosol dust deposition events per units of time
      and area, enrichment factor and the total load allowed to establish that the
      territory of the tailing waste dump site had a snow cover highly contaminated
      with dust deposited at a rate of 247-480 mg/(m2?day). Adjacent areas could be
      considered as area with low Hg contamination rate with average deposition rate of
      30 mg/(m2?day). The elemental composition of the aerosol dust depositions was
      determined as well, which allowed to reveal the extent of enrichment waste
      dispersion throughout adjacent areas. The amount of Hg entering environment with
      snowmelt water discharge was estimated. As a result of snowmelting, in 2014 the
      nearest to the dump site hydrographic network got Hg as 7.1 g with colloids and
      as 5880 g as particles. The results obtained allowed to assess the degree of Hg
      contamination of areas under the impact of metal enrichment industry.

PMID- 29579680
TI  - The antihistamine diphenhydramine is demethylated by anaerobic wastewater
      microorganisms.
AB  - While emerging pharmaceutical contaminants are monitored in wastewater treatment
      and the environment, there is little information concerning their microbial
      metabolites. The transformation of diphenhydramine by microorganisms in anaerobic
      digester sludge was investigated using anaerobic cultures amended with 1 mM
      diphenhydramine as the sole carbon source. Complete transformation of the parent
      compound to a persistent metabolite occurred within 191 days. Using GC/MS
      analysis, the metabolite was identified as N-desmethyl diphenhydramine. Loss of
      the parent compound diphenhydramine followed a first order rate constant of 0.013
      day-1. There was no observed decrease in metabolite concentration even after a
      further 12 months of incubation, suggesting that the metabolite resists further
      degradation during wastewater treatment. Bacterial community diversity in the
      diphenhydramine transforming assay cultures showed enrichment in Comamonadaceae,
      Symbiobacteriaceae, Anaerolineaceae, and Prevotellaceae relative to unamended
      background controls. An anaerobic toxicity assay demonstrated that
      diphenhydramine has an inhibitory effect on both fermentative bacteria and
      methanogenic archaea in the wastewater community. In contrast, the metabolite N
      desmethyl diphenhydramine partially suppressed methanogens but did not impact the
      fermenting community. To our knowledge, this is the first report of
      diphenhydramine metabolism by a bacterial community. The limited transformation
      of diphenhydramine by wastewater microorganisms indicates that N-desmethyl
      diphenhydramine will enter the environment along with unmetabolized
      diphenhydramine.

PMID- 29579681
TI  - Reactive Black 5 as electron donor and/or electron acceptor in dual chamber of
      solar photocatalytic fuel cell.
AB  - The role of azo dye Reactive Black 5 (RB5) as an electron donor and/or electron
      acceptor could be distinguished in dual chamber of photocatalytic fuel cell
      (PFC). The introduction of RB5 in anode chamber increased the voltage generation
      in the system since degradation of RB5 might produce electrons which also would
      transfer through external circuit to the cathode chamber. The removal efficiency
      of RB5 with open and closed circuit was 8.5% and 13.6%, respectively and removal
      efficiency for open circuit was low due to the fact that recombination of
      electron-hole pairs might happen in anode chamber since without connection to the
      cathode, electron cannot be transferred. The degradation of RB5 in cathode
      chamber with absence of oxygen showed that electrons from anode chamber was
      accepted by dye molecules to break its azo bond. The presence of oxygen in
      cathode chamber would improve the oxygen reduction rate which occurred at
      Platinum-loaded carbon (Pt/C) cathode electrode. The Voc, Jsc and Pmax for
      different condition of ultrapure water at cathode chamber also affected their
      fill factor. The transportation of protons to cathode chamber through Nafion
      membrane could decrease the pH of ultrapure water in cathode chamber and undergo
      hydrogen evolution reaction in the absence of oxygen which then increased
      degradation rate of RB5 as well as its electricity generation.

PMID- 29579682
TI  - Association between serum polybrominated diphenyl ethers, new flame retardants
      and thyroid hormone levels for school students near a petrochemical complex,
      South China.
AB  - As surrogates of polybrominated diphenyl ethers (PBDEs), new flame retardants
      (NFRs) include a series of chlorinated and brominated flame retardants. Though
      the NFRs are thought to induce similar thyroid hormone (TH) disrupting effects as
      PBDEs, few studies have focused on them. Given the increasing levels of NFRs in
      the environment, more in depth investigation of the potential TH disrupting
      effects of NFRs is warranted. This research involved a health survey to collect
      data and examine the associations between PBDEs, NFRs and TH. 174 school students
      lived near a petrochemical complex in South China participated in the survey,
      completing questionnaires and providing blood samples. Thirteen congeners of
      PBDEs, eight species of NFRs, TH and thyroid-stimulating hormone (TSH) were
      measured. The median levels of SigmaPBDE (sum of thirteen congeners of PBDEs) and
      SigmaNFR (sum of eight species of NFRs) for students were 140 and 240 ng g-1
      lipid, respectively. Nonmonotonic relationships were observed between quartile
      levels of PBDEs, NFRs and corresponding TH. In contrast to SigmaPBDE that was
      positively associated with triidothyrine (T3) level, SigmaNFR was not
      statistically associated with TH. SigmaPBDE + NFR (sum of thirteen congeners of
      PBDEs and eight species of NFRs) was significantly associated with T3 level.

PMID- 29579683
TI  - Drought promotes increases in total mercury and methylmercury concentrations in
      fish from the lower Paraiba do Sul river, southeastern Brazil.
AB  - Bioaccumulation of mercury and methylmercury in fish represents a serious risk to
      human beings. Extreme climate events like droughts may increase the trophic
      transfer of contaminants and net methylation of mercury. The present study
      assessed the influence of the 2014 drought on total mercury and methylmercury
      levels in fish from the lower Paraiba do Sul river basin. Contaminant levels were
      compared for Pimelodus fur, Pachyurus adspersus, Pimelodella lateristriga,
      Oligosarcus hepsetus, and Crenicichla lacustris captured in five sites in 2013 (N
      = 212) and 2014 (N = 231). The results indicate that levels of contaminants were
      higher during the drought in most species. Rainfall was weakly and negatively
      correlated with total mercury levels in most of the species. The weak
      relationship between these two variables was due to the indirect influence of
      rainfall on mercury bioaccumulation. In summary, drought increased the levels of
      two contaminants in fish.

PMID- 29579684
TI  - Insecticides alter prey choice of potential biocontrol agent Philodromus cespitum
      (Araneae, Philodromidae).
AB  - Even though pesticides can have various sublethal effects on behaviour of
      biocontrol agents, no study to date has investigated the effects of pesticides on
      the prey choice of generalist predators. Prey choice of generalist predators is
      among key factors determining the predation pressure they exert on pests, because
      it influences fitness of predators and consequently their densities and per
      capita capture rate. Here, we investigated the effect of Integro (a.i.
      methoxyfenozide) and SpinTor 480 Sc (a.i. spinosad) on prey choice and predatory
      activity of the spider Philodromus cespitum, which is known significantly to
      reduce hemipteran and dipteran pests in fruit orchards. We compared the prey
      preferences of philodromids between the psyllid pest Cacopsylla pyri (Hemiptera,
      Psyllidae) and beneficial Theridion sp. spiders in laboratory experiments. We
      found that both pesticides altered the prey preferences of philodromids. While
      the philodromids in a control treatment preferred theridiid spiders over the
      psyllid pest, philodromids in the pesticide treatments exhibited no significant
      prey preferences. The changes in prey preferences were caused by increased
      predation on the psyllids, while the predation on the theridiid remained similar.
      We suggest that the changes in prey preferences might theoretically be due to 1)
      impaired sensory systems, 2) altered taste, and/or 3) altered mobility. In
      combination with other studies finding reduced predation on fruit flies in P.
      cespitum after exposure to SpinTor, our results indicate that the sublethal
      effects of pesticides on predatory behaviour of generalist predators can depend
      on prey type and/or prey community composition.

PMID- 29579685
TI  - Impact of insulin signaling and proteasomal activity on physiological output of a
      neuronal circuit in aging Drosophila melanogaster.
AB  - The insulin family of growth factors plays an important role in development and
      function of the nervous system. Reduced insulin and insulin-growth-factor
      signaling (IIS), however, can improve symptoms of neurodegenerative diseases in
      laboratory model organisms and protect against age-associated decline in neuronal
      function. Recently, we showed that chronic, moderately lowered IIS rescues age
      related decline in neurotransmission through the Drosophila giant fiber escape
      response circuit. Here, we expand our initial findings by demonstrating that
      reduced functional output in the giant fiber system of aging flies can be
      prevented by increasing proteasomal activity within the circuit. Manipulations of
      IIS in neurons can also affect longevity, underscoring the relevance of the
      nervous system for aging.

PMID- 29579686
TI  - Cerebral microhemorrhages due to traumatic brain injury and their effects on the
      aging human brain.
AB  - Although cerebral microbleeds (CMBs) are frequently associated with traumatic
      brain injury (TBI), their effects on clinical outcome after TBI remain
      controversial and poorly understood, particularly in older adults. Here we (1)
      highlight major challenges and opportunities associated with studying the effects
      of TBI-mediated CMBs; (2) review the evidence on their potential effects on
      cognitive and neural outcome as a function of age at injury; and (3) suggest
      priorities for future research on understanding the clinical implications of
      CMBs. Although TBI-mediated CMBs are likely distinct from those due to cerebral
      amyloid angiopathy or other neurodegenerative diseases, the effects of these 2
      CMB types on brain function may share common features. Furthermore, in older TBI
      victims, the incidence of TBI-mediated CMBs may approximate that of cerebral
      amyloid angiopathy-related CMBs, and thus warrants detailed study. Because the
      alterations effected by CMBs on brain structure and function are both unique and
      age-dependent, it seems likely that novel, age-tailored therapeutic approaches
      are necessary for the adequate clinical interpretation and treatment of these
      ubiquitous and underappreciated TBI sequelae.

PMID- 29579688
TI  - Cluster analysis of autism spectrum disorder symptomatology: Qualitatively
      distinct subtypes or quantitative degrees of severity of a single disorder?
AB  - The decision to collapse several related disorders into a single diagnosis of
      Autism Spectrum Disorder (ASD) generated significant controversy and debate.
      There has been mixed evidence as to whether various ASD subtypes are
      qualitatively distinct or if they exist on a spectrum of symptom severity. The
      present study conducted a two-step cluster analysis of major ASD symptoms in a
      sample of 147 young males with ASD aged between 6yr and 18yr with IQ > 70.
      Results indicated that a two-cluster solution (high and low severity of ASD
      symptomatology) was reliable and valid. Further, the construct of challenging
      behaviour was not a necessary component of the two-cluster solution, verifying
      the new conceptualisation of ASD. Further replication of these findings with
      other subsets of individuals with ASD is needed.

PMID- 29579689
TI  - Improved production of isobutanol in pervaporation-coupled bioreactor using
      sugarcane bagasse hydrolysate in engineered Enterobacter aerogenes.
AB  - A process of isobutanol production from sugarcane bagasse hydrolysates in
      Enterobacter aerogenes was developed here with a pervaporation-integrated
      procedure. Isobutanol pathway was overexpressed in a mutant strain with
      eliminated byproduct-forming enzymes (LdhA, BudA, and PflB). A glucose-and-xylose
      coconsuming ptsG mutant was constructed for effective utilization of
      lignocellulosic biomass. Toxic effects of isobutanol were alleviated by in situ
      recovery via a pervaporation procedure. Compared to single-batch fermentation,
      cell growth and isobutanol titer were improved by 60% and 100%, respectively, in
      the pervaporation-integrated fermentation process. A lab-made cross-linked
      polydimethylsiloxane membrane was cast on polyvinylidene fluoride and used in the
      pervaporation process. The membrane-penetrating condensate contained 55-226 g m-2
      h-1 isobutanol with 6-25 g L-1 ethanol after separation. This study offers
      improved fermentative production of isobutanol from lignocellulosic biomass with
      a pervaporation procedure.

PMID- 29579687
TI  - Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and
      hippocampal amyloid beta-peptide levels, without discernable behavioral effects
      in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) involves progressive deposition of amyloid beta-peptide
      (Abeta), synapse loss, and neuronal death, which occur in brain regions critical
      for learning and memory. Considerable evidence suggests that lipid peroxidation
      contributes to synaptic dysfunction and neuronal degeneration, both upstream and
      downstream of Abeta pathology. Recent findings suggest that lipid peroxidation
      can be inhibited by replacement of polyunsaturated fatty acids (PUFA) with
      isotope-reinforced (deuterated) PUFA (D-PUFA), and that D-PUFA can protect
      neurons in experimental models of Parkinson's disease. Here, we determined
      whether dietary D-PUFA would ameliorate Abeta pathology and/or cognitive deficits
      in a mouse model of AD (amyloid precursor protein/presenilin 1 double mutant
      transgenic mice). The D-PUFA diet did not ameliorate spatial learning and memory
      deficits in the AD mice. Compared to mice fed an hydrogenated-PUFA control diet,
      those fed D-PUFA for 5 months exhibited high levels of incorporation of deuterium
      into arachidonic acid and docosahexaenoic acid, and reduced concentrations of
      lipid peroxidation products (F2 isoprostanes and neuroprostanes), in the brain
      tissues. Concentrations of Abeta40 and Abeta38 in the hippocampus were
      significantly lower, with a trend to reduced concentrations of Abeta42, in mice
      fed D-PUFA compared to those fed hydrogenated-PUFA. We conclude that a D-PUFA
      diet reduces the brain tissue concentrations of both arachidonic acid and
      docosahexaenoic acid oxidation products, as well as the concentration of Abetas.

PMID- 29579691
TI  - Microbial communities underpinning mesophilic anaerobic digesters treating food
      wastewater or sewage sludge: A full-scale study.
AB  - Ten mesophilic full-scale anaerobic digesters treating food wastewater (FW
      digesters) or sewage sludge (SL-digesters) were monitored for 1 year to
      investigate: (1) microbial communities underpinning FW-digesters and SL
      digesters, (2) the effects of total ammonia-nitrogen concentration [TAN] and Na+
      concentration [Na+] on variations of these communities. [TAN] and [Na+] in the
      digester varied among digesters: 1.7-6.5 g TAN/L and 1.0-3.6 g Na+/L for the FW
      digesters, and 0.1-2.2 g TAN/L and 0.1-1.2 g Na+/L for the SL-digesters; [TAN]
      negatively correlated with the process efficiency of the FW-digesters. Microbial
      communities were less diverse in the FW-digesters than in the SL-digesters. The
      FW- and SL-digesters formed very distinct microbial community structures; [TAN]
      and [Na+] in the digester were the critical factors shaping these structures.
      Immigrant bacteria from influent sludge significantly influence the bacterial
      communities of the SL-digesters. Methanoculleus might be tolerant to high ammonia
      in AD of such organic wastewater.

PMID- 29579690
TI  - A novel approach to developing a reusable marine macro-algae adsorbent with
      chitosan and ferric oxide for simultaneous efficient heavy metal removal and easy
      magnetic separation.
AB  - Chitosan modified magnetic kelp biochar (Chi-KBm) was successfully synthesized
      for efficient removal of heavy metals (Cu2+) from wastewater. Interestingly, the
      characterization results indicated that Chi-KBm showed 6 times higher surface
      area (6.17 m2/g) than the pristine magnetic kelp biochar KBm (0.97 m2/g). In
      addition, new functional groups, such as NH and CN group, have been created on
      the surface of biochar as a result of chitosan modification process, which in
      turns led to improve the Cu2+ adsorption capacity. The effect of pH and chitosan
      loading on heavy metal adsorption, and competition reaction of different metal
      ions adsorption were also investigated. Chi-KBm exhibited a separation efficiency
      of more than 99.8%, which allows to recovery and reusability of the adsorbent
      material and heavy metals simultaneously. Overall, this study highlighted the Chi
      KBm is a promise adsorbent for heavy metal removal without sacrificing of the
      separation ability using magnetism.

PMID- 29579692
TI  - Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer:
      A review.
AB  - Prostate-specific antigen (PSA) is a serine protease produced by epithelial
      prostatic cells and its main function is to liquefy seminal coagulum. Currently,
      PSA is a biomarker for the diagnosis and screening of prostate cancer and it was
      the first cancer biomarker approved by the FDA. The quantity and serum isoforms
      of male PSA, allows distinguishing between carcinoma and benign inflammatory
      disease of the prostate. Initially, it was thought that PSA was produced only by
      the prostate, and thus, a protein that was expressed exclusively in men. However,
      several authors report that PSA is a protein that is expressed by multiple non
      prostatic tissues not only in men but also in women. Some authors also report
      that in women, the expression of this protein is highly related to breast and
      colon cancer and therefore can act as a possible biomarker for early detection,
      diagnosis and prognosis of these cancers in women. In this review, we will focus
      on the characteristics of the PSA at a molecular level, its current clinical
      implications, the expression of this protein in non-prostatic tissues, and its
      relationship with cancer, especially in women.

PMID- 29579693
TI  - Secretins revealed: structural insights into the giant gated outer membrane
      portals of bacteria.
AB  - The acquisition and evolution of customized and often highly complex secretion
      systems allows Gram-negative bacteria to efficiently passage large macromolecules
      across both inner and outer membranes and, in some cases, that of the infected
      host. Essential to the virulence and ultimate survival of the many pathogenic
      species that encode them, secretion systems export a wide variety of effector
      proteins and DNA as well as the downstream extracellular filaments of the
      secretion apparatus themselves. Although these customized secretion systems
      differ in their cytosolic and inner membrane components, several commonly rely on
      the secretin family of giant pores to allow these large substrates to traverse
      the outer membrane. Recently, several near-atomic resolution cryo-EM secretin
      structures have unveiled the first insights into the unique structural motifs
      required for outer membrane localization, assembly, hallmark ultrastable nature,
      spontaneous membrane insertion, and mechanism of action-including the requisite
      central gating needed to prevent deleterious passage of periplasmic contents to
      the extracellular space.

PMID- 29579694
TI  - Translocation of lipoproteins to the surface of gram negative bacteria.
AB  - The surface of many Gram-negative bacteria contains lipidated protein molecules
      referred to as surface lipoproteins or SLPs. SLPs play critical roles in host
      immune evasion, nutrient acquisition and regulation of bacterial stress response,
      and have been extensively studied as vaccine antigens. The aim of this review is
      to summarize the recent studies that have investigated the biosynthetic and
      translocation pathways used by different bacterial species to deliver SLPs to the
      surface. We will specifically focus on Slam, a novel outer membrane protein first
      discovered in pathogenic Neisseria sp., that is involved in translocation of SLPs
      across the outer membrane.

PMID- 29579695
TI  - 'They'll be judging us' a qualitative study of pregnant women's experience of
      being offered participation in a supportive intervention.
AB  - OBJECTIVE: to explore pregnant women's experience of being offered participation
      in a supportive intervention and how their experience influenced the outcome of
      the intervention. DESIGN AND SETTING: a qualitative, phenomenological hermeneutic
      study based on semi-structured interviews with eight Danish first-time mothers.
      FINDINGS: the study revealed a divergence between the professional's and the
      women's perception of their vulnerability. The women typically felt the offer of
      participation as a stigma, which they met with anxiety and confusion.
      Insufficient information led to uncertainty and a feeling of being evaluated as
      inadequate mothers or parents. The information offered failed to provide the
      basis of informed choice. However, the development of a trusting, supportive and
      non-judgemental relationship with the health professionals ensured most women a
      positive outcome of the intervention. KEY CONCLUSION: being invited to
      participate in an intervention targeting vulnerable women may induce unintended
      feelings in relation to stigmatization and judgement, leading to doubt about own
      ability to cope with motherhood. Inadequate information and explication about
      aims and contents of the intervention are likely to cause confusion and anxiety
      and a feeling of being judged as parents. Information combined with establishing
      a trusting and non-judgemental relationship between women and professionals
      appears to have significant impact on outcomes. IMPLICATIONS FOR PRACTICE: care
      providers should be aware of the induced negative feelings and sense of judgement
      and stigmatization as a result of being categorized as vulnerable and perceived
      in need of help to cope with motherhood, and that they may play a key role in
      helping women cope with this. Furthermore, detailed information about the
      intervention and the background of the offer should be ensured as well as an
      informed choice of participation.

PMID- 29579696
TI  - Support for pregnant women identified with fear of childbirth (FOC)/tokophobia -
      A systematic review of approaches and interventions.
AB  - BACKGROUND: providing appropriate care for pregnant women with high or severe
      fear of childbirth (FOC) is a challenge in midwifery care today. FOC is
      associated with predisposing anamnestic factors, various sociodemographic and
      psychosocial characteristics, and may result in serious healthrelated
      consequences. It is therefore important to establish which interventions may
      increase a woman's faith in her own ability to cope with labour and birth. AIM:
      to systematically identify and review studies examining interventions for relief
      of severe fear of childbirth in pregnancy and their underlying conceptual
      foundation. METHODS: a systematic literature search was performed following
      Cochrane Collaboration and PRISMA Statement recommendations. Inclusion criteria
      were: studies including pregnant women diagnosed with high or severe FOC or who
      requested a caesarean section due to severe FOC, studies (regardless of design)
      observing the effect of an intervention addressing FOC, and studies published in
      English. Publications addressing anxiety or stress were excluded. 377 references
      were screened by title and abstract. The risk of bias was assessed. FINDINGS: 19
      articles referring to 15 research projects were included in the analysis. The
      studies show heterogeneity regarding assessment methods, type, conceptualisation
      and application of interventions. There is evidence that both cognitive therapy
      sessions and a theory-based group psychoeducation with relaxation are effective
      interventions. KEY CONCLUSIONS: despite methodological limitations, single or
      group psychoeducation sessions for nulliparous women or therapeutic conversation
      during pregnancy (in group or individual sessions) have the potential to
      strengthen women's self-efficacy and decrease the number of caesarean sections
      due to FOC. The theoretical validation of an intervention deepens the
      understanding of psychological processes in women coping with severe FOC.
      IMPLICATIONS FOR PRACTICE: theory-based concepts of care for both antenatal and
      intrapartum support of pregnant women with high or severe FOC should be
      developed, piloted, tested, evaluated and implemented within the given healthcare
      system. Midwives need to be competent to address pregnant women's fears regarding
      labour and birth in antenatal care. The use of a valid assessment tool to
      identify the level of FOC in women, even if they do not raise the issue, is
      recommended in routine antenatal care so that appropriate expert support can be
      offered. A one-on-one conversation may be feasible for those women unwilling to
      fill in a questionnaire. Cooperative local networks between midwives,
      psychologists and obstetricians qualified in psychotherapy should be established
      to ensure timely and effective care for women with high or severe FOC.

PMID- 29579697
TI  - Neighborhood social and economic change and retail food environment change in
      Madrid (Spain): The heart healthy hoods study.
AB  - This study explores the association between neighborhood social and economic
      change from 2009 to 2013 and changes in the retail food environment from 2013 to
      2017 in Madrid (Spain). We classified neighborhoods into four types: decreasing
      SES, new housing/gentrifying, increasing SES, and aging (population and housing).
      Food store data was obtained from a retail spaces census and classified as
      supermarket, specialized small store, or fruit and vegetable store. Compared to
      aging areas, new housing/gentrifying and areas with increasing SES had a higher
      baseline presence and proportion of supermarkets and a lower proportion of
      specialized stores and fruit and vegetable stores. Areas with decreasing SES had
      an initially higher presence and proportion of fruit and vegetable stores but
      showed a declining trend in both presence and proportion of fruit and vegetable
      stores.

PMID- 29579698
TI  - Understanding temporal change of spatial accessibility to healthcare: An analytic
      framework for local factor impacts.
AB  - Population demand, health service supply, and the linkages between them (e.g.,
      transport infrastructure) are important factors that determine spatial
      accessibility to healthcare at a place. These three factors vary differently over
      time and location, leading to temporal changes and spatial disparities in access
      to healthcare. Few analytic methods have been developed to measure local impacts
      of these factors on healthcare accessibility over time, which are essential to
      alleviating health disparities and evaluating intervention programs. We propose a
      spatially explicit analytic framework to measure local factor impacts over time
      by adopting a chain substitution method from economics. The analysis is
      illustrated by a case study of spatial accessibility to physicians in Florida,
      USA, from 1990 to 2010. For each census block group, the results show the impact
      of local population change, physician relocation, and road-network expansion on
      the loss and gain of healthcare accessibility over time. The leading impact
      factor are identified for each census block group through comparison, and spatial
      clusters of factor impacts are discovered. To the literature of healthcare
      accessibility, this article presents a promising start of factor impact analysis
      and offers new perspectives in exploring spatial processes underlying people's
      access to healthcare.

PMID- 29579699
TI  - Social cohesion and self-rated health among adults in South Africa: The
      moderating role of race.
AB  - In African countries including South Africa, the nexus between social cohesion
      and health remains under-researched. Using data from the 2012 South African
      social attitudes survey with a sample of 1988 adults in South Africa aged 18
      years or older, we used the collective efficacy theory by Sampson and colleagues
      to examine the relationship between social cohesion and self-rated health in an
      African sample. We also examined how this relationship differed by race. Results
      from the multivariate analysis after adjusting for covariates suggested that
      adults in the highest tertile of social cohesion were more likely to report
      moderate or good health compared to those in the lowest tertile. Sub-group
      analysis provided no evidence that the relationship was moderated by race. These
      findings corroborate prior evidence that social cohesion is important for
      improving the health of adults.

PMID- 29579700
TI  - The associations between interpersonal violence and psychological distress among
      rural and urban young women in South Africa.
AB  - BACKGROUND: Approximately 25% of the world's population consists of young people.
      The experience of violence peaks during adolescence and the early adult years. A
      link between personal experience of violence and mental health among young people
      has been demonstrated but rural-urban differences in these associations are less
      well known in low to middle income countries. The aim of this study was to
      investigate the associations between interpersonal violence and psychological
      distress among rural and urban young women. METHODS: Data on experiences of
      violence and psychological distress were collected from a total of 926 non
      pregnant young women aged between 18 and 22 years of age in rural and urban sites
      in South Africa. The General Health Questionnaire-28 was used to assess
      psychological distress as an indicator of mental health. Generalised structural
      equation models were employed to assess potential pathways of association between
      interpersonal violence and psychological distress. RESULTS: Thirty-four percent
      of the urban young women (n = 161) reported psychological distress compared to
      18% of rural young women (n = 81). In unadjusted analysis, exposure to
      interpersonal violence doubled the odds of psychological distress in the urban
      adolescents and increased the odds 1.6 times in the rural adolescents. In
      adjusted models, the relationship remained significant in the urban area only (OR
      1.84, 95% CI 1.13-3.00). Rural residence seemed protective against psychological
      distress (OR 0.41, 95% CI 0.24-0.69). Structural equation modelling did not
      reveal any direct association between exposure to interpersonal violence and
      psychological distress among rural young women. Stressful household events were
      indirectly associated with psychological distress, mediated by violence among
      young women in the urban area. CONCLUSION: The relationship between violence and
      psychological distress differs between urban and rural-residing young women in
      South Africa, and is influenced by individual, household and community
      (contextual) factors.

PMID- 29579701
TI  - Gait deviations in Duchenne muscular dystrophy-Part 1. A systematic review.
AB  - BACKGROUND: Although prolonged ambulation is considered important in children
      with Duchenne muscular dystrophy (DMD), articles describing gait deviations in
      DMD are scarce. RESEARCH QUESTION: Therefore, our research questions were the
      following: 1) what are the most consistently reported spatiotemporal-, kinematic
      , kinetic-, and muscle activity deviations in children with DMD in literature, 2)
      what is the quality of the studies describing these deviations, and 3) is there
      need for further research? METHODS: We conducted a systematic literature search
      for studies published before the end of June 2017 in six online databases. We
      created a data extraction form to define information on materials and methods and
      on the analyzed gait parameters for each paper included in the review. If enough
      information was available, we calculated standardized mean differences (SMDs).
      RESULTS: The search yielded nine articles, but generalizability was poor. Seventy
      nine parameters were analyzed by seven research groups, but they only agreed on a
      decrease in walking speed (minimal SMD: 1.26), stride length (1.83), step length
      (1.80), dorsiflexion during swing (1.43), maximal power generation at the hip
      (0.92), maximal knee extension torque (0.99), maximal dorsiflexion torque (
      1.30), and maximal power generation at the ankle (0.92), and an increased knee
      range of motion (-0.82) in DMD. SIGNIFICANCE: In order to keep children with DMD
      ambulant as long as possible, a clear understanding of their pathological gait
      pattern is necessary. However, gait deviations in DMD appear not well defined.
      Previous studies appear to be of an exploratory nature while using predefined
      gait parameters to assess an undirected null hypothesis. This made them prone to
      regional focus bias, thereby increasing the chance of a type I error. Therefore,
      further research is required to define the altered gait pattern in children with
      DMD.

PMID- 29579702
TI  - Gait and footwear in children and adolescents with Charcot-Marie-Tooth disease: A
      cross-sectional, case-controlled study.
AB  - OBJECTIVE: Children with Charcot-Marie-Tooth disease (CMT) report problems with
      gait and footwear. We evaluated differences in spatio-temporal gait variables and
      gait variability between children with CMT and typically developing (TD)
      children, and investigated the effect of footwear upon gait. METHOD: A cross
      sectional study of 30 children with CMT and 30 age- and gender-matched TD
      children aged 4-18 years. Gait was assessed at self-selected speed on an
      electronic walkway while barefoot and in two types of the child's own footwear;
      optimal (e.g., athletic-type runners) and suboptimal (e.g., flip-flops). RESULTS:
      Children with CMT walked more slowly (mean (SD) -13.81 (3.61) cm/s), with shorter
      steps (-6.28 (1.37) cm), wider base of support (+2.47 (0.66) cm; all p < 0.001)
      and greater base of support variability (0.48 (0.15) cm, p = 0.002) compared to
      TD children. Gait was faster in optimal footwear than suboptimal (-7.55 (1.31)
      cm/s) and barefoot (-7.42 (1.07) cm/sec; both p < 0.001) in the combined group of
      children. Gait in suboptimal footwear was more variable compared to barefoot and
      optimal footwear. Greater base of support variability and reduced balance was
      moderately correlated for both groups (CMT and TD). CONCLUSION: Gait is slower
      with shorter, wider steps and greater base of support variability in children
      with CMT. Poor balance is associated with greater base of support gait
      variability. Suboptimal footwear negatively affects gait in all children (CMT and
      TD), which has clinical implications for children and adolescents with CMT who
      have weaker feet and ankles, and poor balance.

PMID- 29579703
TI  - Backbone amide 15N chemical shift tensors report on hydrogen bonding interactions
      in proteins: A magic angle spinning NMR study.
AB  - Chemical shift tensors (CSTs) are an exquisite probe of local geometric and
      electronic structure. 15N CST are very sensitive to hydrogen bonding, yet they
      have been reported for very few proteins to date. Here we present experimental
      results and statistical analysis of backbone amide 15N CSTs for 100 residues of
      four proteins, two E. coli thioredoxin reassemblies (1-73-(U-13C,15N)/74-108-(U
      15N) and 1-73-(U-15N)/74-108-(U-13C,15N)), dynein light chain 8 LC8, and CAP-Gly
      domain of the mammalian dynactin. The 15N CSTs were measured by a symmetry-based
      CSA recoupling method, ROCSA. Our results show that the principal component
      delta11 is very sensitive to the presence of hydrogen bonding interactions due to
      its unique orientation in the molecular frame. The downfield chemical shift
      change of backbone amide nitrogen nuclei with increasing hydrogen bond strength
      is manifested in the negative correlation of the principal components with
      hydrogen bond distance for both alpha-helical and beta-sheet secondary structure
      elements. Our findings highlight the potential for the use of 15N CSTs in protein
      structure refinement.

PMID- 29579704
TI  - Chitooligosaccharide: An evaluation of physicochemical and biological properties
      with the proposition for determination of thermal degradation products.
AB  - Being the most versatile biopolymer, chitooligosaccharide/chitosan
      oligosaccharide (COS) has been extensively studied for a range of exceptional
      biological activities and potential developments of novel medical devices and
      systems in biomedical and pharmaceutical fields. While possessing intrinsic
      biocompatibility, mucoadhesiveness, and non-toxicity it gained more interests in
      the biomedical development of novel systems, devices, and pharmaceutical
      formulations. The bioactive relativity of chitosan and COS are of highly
      significant and thus explored in this paper while highlighting its multiple
      biological activities and promising biomedical applications. More emphasis is on
      the molecular weight, degree of acetylation/deacetylation, degree of
      polymerization and reactive groups in relation to chitin and chitosan. Despite
      COS wide acceptance and utilization, the associated viscosity and instability are
      crucial factors that posed a great challenge to researchers. The apparent reason
      attributed to instability and viscosity could be the presence intrinsic variable
      oligomers within COS. Due to lack of data on safety and impurity analysis of
      thermal exposure of COS, we hypothesized that different molecules could be
      generated with thermal treatment of COS, thus finally suggested a prospective
      determination of thermal degradation product(s)in COS. Hence the aim of this
      paper is to highlight COS physicochemical and biological significance with
      reference to its recent developments and propose a further chemical analysis
      thermal treated COS. This could trigger future researchers for possible isolation
      and characterization of distinct biomolecules from COS.

PMID- 29579705
TI  - LncRNA SNHG6 acts as a prognostic factor to regulate cell proliferation in glioma
      through targeting p21.
AB  - It has been certified that long noncoding RNAs (lncRNAs) are crucial regulators
      in the progression of various human cancers. snoRNA host gene 6 (SNHG6) has been
      uncovered to affect the initial stage and tumorigenesis of hepatocellular
      carcinoma. Nevertheless, the expression pattern and biological role of SNHG6 in
      glioma still need to be investigated. The study aims to investigate the
      expression pattern, biological role and the potential mechanism of SNHG6 in
      glioma. In this study, the high expression of SNHG6 was tested in both glioma
      tissues and glioma cells. The correlation between expression levels of SNHG6 and
      the overall survival of glioma patients was demonstrated by using Kaplan Meier
      method analysis. Next, gain of function assays revealed that overexpression of
      SNHG6 can promote the formation of malignant phenotype of 1800 cell. However,
      results of loss-of-function assays revealed that silenced SNHG6 exerted the
      inhibitory function on glioma cell growth. Flow cytometric analysis was performed
      in glioma cells to detect the anti-oncogenic effects of silenced SNHG6 on cell
      cycle and apoptosis. Finally, we identified that p21 was involved in glioma cell
      proliferation after SNHG6 was downregulated. Taken together, we concluded that
      SNHG6 is a regulator and a potential therapeutic target in glioma.

PMID- 29579706
TI  - Molecular basis of vascular damage caused by cigarette smoke exposure and a new
      approach to the treatment: Alpha-linolenic acid.
AB  - Exposure to cigarette smoke (CS) causes vessel damage and mechanism of this
      damage has not yet been clearly identified. Therefore, in this study we aimed to
      investigate whether vessel damage due to the CS exposure will be prevented by the
      alpha-linolenic acid (ALA) or not which has anti-inflammatory effect in mice. For
      this reason, mice were grouped as controls (with and without CS) and ALA (with
      and without CS). The CS application continued 5 days a week for two months. At
      the end of two months, the mice were killed by cervical dislocation and their
      blood and thoracic aortas were isolated. ALA Treatment increased acetylcholine
      relaxations. CS decreased acetylcholine relaxation. CS with ALA treatment
      increased acetylcholine relaxations versus just CS treatment. CS caused rising in
      cyclooxigenase-2 and phospholipase A2 levels. This rise is inhibited with ALA
      treatment. CS decreased eNOS levels. But this result was not statistically
      significant. Furthermore, according to electron microscopic study CS damaged both
      smooth muscle and endothelium. While ALA treatment prevented smooth muscle damage
      it didn't prevent endothelial damage. Using cigarette and CS exposure is a risk
      factor for cardiovascular disease. Our study showed that this disease.

PMID- 29579707
TI  - Arctigenin protects against liver injury from acute hepatitis by suppressing
      immune cells in mice.
AB  - As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants,
      such as those used in traditional Chinese herbal medicine, including Arctium
      lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and
      anticancer activities. In this study, we investigated the protective role of
      arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin
      remarkably reduced the congestion and necroinflammation of livers, and improved
      hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo. The
      infiltration of CD4 T, NKT and macrophages into the livers was found to be
      reduced with arctigenin treatment. Arctigenin suppressed ConA-induced T
      lymphocyte proliferations that might have resulted from enhanced IL-10 production
      by macrophages and CD4 T cells. These results suggested that arctigenin could be
      a powerful drug candidate for acute hepatitis through immune suppression.

PMID- 29579708
TI  - Punicalagin ameliorates the elevation of plasma homocysteine, amyloid-beta, TNF
      alpha and apoptosis by advocating antioxidants and modulating apoptotic mediator
      proteins in brain.
AB  - The present study investigated the neuroprotective role of punicalagin, a major
      polyphenolic compound of pomegranate on methionine-induced brain injury.
      Hyperhomocysteinemia (HHcy) was induced in two months old male BALB c mice by
      methionine supplementation in drinking water (1 g/kg body weight) for 30 days.
      Punicalagin (1 mg/kg) was injected i.p every other day concurrently with
      methionine. Punicalagin significantly prevented the rise in the levels of
      homocysteine, amyloid-beta and TNF-alpha. HHcy is associated with a decrease in
      the activities of superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (PGx) and glutathione reductase (GR) and glutathione (GSH) levels in
      the brains of methionine-treated mice while these antioxidants are increased by
      punicalagin supplementation. The treatment with punicalagin significantly
      decreased oxidative stress as indicated by decreased malondialdehyde and protein
      carbonyl formation in the brain. Compared with methionine-treated animals, mice
      that treated with methionine and punicalagin remarkably displayed less apoptosis,
      indicated by the lower level of proapoptotic protein (Bax, caspases- 3, 9 and
      p53) and higher levels of antiapoptotic Bcl-2 protein than those in
      hyperhomocysteinemic mice. The potent bioactivity of punicalagin extends to
      protect neuronal DNA as evidenced by the inhibition of the increase of comet
      parameters compared to the methionine-treated mice. In conclusion, punicalagin
      protected from methionine-induced HHcy and brain damage with an ability to
      repress apoptosis by modulating apoptotic mediators and maintaining DNA integrity
      in the brain of mice.

PMID- 29579709
TI  - The novel piperazine-containing compound LQFM018: Necroptosis cell death
      mechanisms, dopamine D4 receptor binding and toxicological assessment.
AB  - Piperazine is a promising scaffold for drug development due to its broad spectrum
      of biological activities. Based on this, the new piperazine-containing compound
      LQFM018 (2) [ethyl 4-((1-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl)piperazine-1
      carboxylate] was synthetized and some biological activities investigated. In this
      work, we described its ability to bind aminergic receptors, antiproliferative
      effects as well as the LQFM018 (2)-triggered cell death mechanisms, in K562
      leukemic cells, by flow cytometric analyses. Furthermore, acute oral systemic
      toxicity and potential myelotoxicity assessments of LQFM018 (2) were carried out.
      LQFM018 (2) was originally obtained by molecular simplification from LASSBio579
      (1), an analogue compound of clozapine, with 33% of global yield. Binding profile
      assay to aminergic receptors showed that LQFM018 (2) has affinity for the
      dopamine D4 receptor (Ki = 0.26 MUM). Moreover, it showed cytotoxicity in K562
      cells, in a concentration and time-dependent manner; IC50 values obtained were
      399, 242 and 119 MUM for trypan blue assay and 427, 259 and 50 MUM for MTT method
      at 24, 48 or 72 h, respectively. This compound (427 MUM) also promoted increase
      in LDH release and cell cycle arrest in G2/M phase. Furthermore, it triggered
      necrotic morphologies in K562 cells associated with intense cell membrane rupture
      as confirmed by Annexin V/propidium iodide double-staining. LQFM018 (2) also
      triggered mitochondrial disturb through loss of DeltaPsim associated with
      increase of ROS production. No significant accumulation of cytosolic cytochrome c
      was verified in treated cells. Furthermore, it was verified an increase of
      expression of TNF-R1 and mRNA levels of CYLD with no involviment in caspase-3 and
      -8 activation and NF-kappaB in K562 cells. LQFM018 (2) showed in vitro
      myelotoxicity potential, but it was orally well tolerated and classified as UN
      GHS category 5 (LD50 > 2000-5000 mg/Kg). Thus, LQFM018 (2) seems to have a non
      selective action considering hematopoietic cells. In conclusion, it is suggested
      LQFM018 (2) promotes cell death in K562 cells via necroptotic signaling, probably
      with involvement of dopamine D4 receptor. These findings open new perspectives in
      cancer therapy by use of necroptosis inducing agents as a strategy of reverse
      cancer cell chemoresistance.

PMID- 29579710
TI  - Bu-shen-zhu-yun decoction promotes synthesis and secretion of FSHbeta and LHbeta
      in anterior pituitary cells in vitro.
AB  - Luteal phase defects (LPD) are an important etiology of infertility which has
      increased in recent years. Studies have shown that bu-shen-zhu-yun decoction
      (BSZY-D) can lower the expression of estrogen receptor and progesterone receptor,
      in rats endometrium of embryonic implantation period, which upregulated by
      mifepristone, and improve uterine receptivity. The aim of present study was to
      determine the effect of BSZY-D on the synthesis and secretion of gonadotropic
      hormones in the anterior pituitary cells of rats. Rats were treated with saline
      (control) or BSZY-D two times/day for three estrous cycles by gavage. The
      cerebrospinal fluid (CSF) were collected for further cell treatment. The
      components in BSZY-D, serum and CSF were analysed by High Performance Liquid
      Chromatography (HPLC). Cells were either pretreated with normal CSF or BSZY-D/CSF
      before being stimulated with or without cetrorelix. The mRNA and proteins levels
      of receptors, hormones, and transcription factors were detected by RT-PCR,
      western blot analysis and immunostaining. We show that non-toxic concentrations
      of cetrorelix, a GnRH antagonist, can reduce the mRNA and protein levels of
      GnRHR, LH, and FSH. This effect could be reversed by the addition of BSZY-D/CSF.
      We also show decreased mRNA and protein expression of transcription factors, such
      as CREB, and Egr-1 and secretory vescicles, including SNAP-25 and Munc-18 upon
      treatment with cetrorelix could be reversed post co-treatment with BSZY-D/CSF.
      These results indicate that BSZY-D/CSF treatment led to increased levels of
      GnRHR, transcription factors, and secretory vesicles leading to increased
      secretion of FSH and LH. Thus, BSZY-D presents a promising candidate to treat
      luteal phase defects and infertility.

PMID- 29579711
TI  - Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and
      induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors
      and is known to be lack of effective therapy. Thus, novel therapeutic strategies
      are greatly needed for treatment of ESCC. Osthole, a natural active extract, has
      been documented to have anti-tumor activity. However, the effect of osthole on
      ESCC cells has not been elucidated. In this study, we demonstrated that osthole
      could inhibit the ESCC cell proliferation in dose- and time-dependent manner.
      Osthole treatment also induced G2/M phase arrest and apoptosis of ESCC cells.
      Furthermore, upon exposure to osthole, the expression of Cyclin B1, Cdc2, Bcl-2,
      PARP1 and Survivin was decreased, while the expression of BAX, cleaved PARP1,
      cleaved Caspase3 and cleaved Caspase9 was increased. In addition, osthole
      treatment elicited upregulation of PTEN and downregulation of PI3K and
      phosphorylated AKT (p-AKT). Taken together, our study demonstrates that osthole
      could suppress ESCC proliferation through inducing cell cycle arrest and
      apoptosis. Moreover, PTEN-PI3K/AKT signaling pathway can be regulated by osthole.
      Our results indicate that osthole may find therapeutic application in the
      treatment of ESCC patients.

PMID- 29579712
TI  - Ginkgetin ameliorates experimental atherosclerosis in rats.
AB  - Atherosclerosis is a common disease seriously detrimental to human health.
      Natural products are important sources of therapeutic candidates for
      atherosclerosis. We here evaluated the effects of ginkgetin on experimental
      atherosclerosis in rats and explored the underlying mechanisms. Atherosclerosis
      was induced by high-fat diet for 12 weeks combined with single intraperitoneal
      injection of vitamin D3 in rats. The atherosclerotic rats were then treated with
      ginkgetin at 25, 50 and 100 mg/kg/d or simvastatin at 2 mg/kg/d for 8 weeks.
      Blood and thoracic aortas were collected for analyses of histopathology, lipid
      deposition, serum biochemistry, matrix metalloproteinases (MMPs), and nitric
      oxide (NO)/NO synthase (NOS) system. We found that ginkgetin improved thoracic
      aortic intima structure, reduced intima-media thickness and intima/media ratio,
      and attenuated lipid deposition in aorta of atherosclerotic rats. Ginkgetin also
      decreased the serum levels of total cholesterol, triglyceride and low-density
      lipoprotein cholesterol, but restored the serum levels of high-density
      lipoprotein cholesterol in atherosclerotic rats. Additionally, ginkgetin reduced
      the mRNA and protein expression of MMP-2 and MMP-9 in thoracic aortas of rats
      with atherosclerosis. Further examinations showed that ginkgetin increased the NO
      and NOS levels in serum and thoracic aortas. Ginkgetin also unregulated the
      expression of endothelial NOS and downregulated the expression of inducible NOS
      at both mRNA and protein levels in thoracic aortas of atherosclerotic rats.
      Altogether, ginkgetin showed therapeutic effects on experimental atherosclerosis
      associated with improving lipid profile and modulating the MMPs and NO/NOS
      systems in rats. Ginkgetin could be a promising candidate for the treatment of
      atherosclerosis.

PMID- 29579714
TI  - Two colorimetric and ratiometric fluorescence probes for hydrogen sulfide based
      on AIE strategy of alpha-cyanostilbenes.
AB  - Aggregation-induced emission (AIE) active fluorescent probes have attracted great
      potential in biological sensors. In this paper two cyanostilbene based
      fluorescence chemoprobe Cya-NO2 (1) and Cya-N3 (2) were developed and evaluated
      for the selective and sensitive detection of hydrogen sulfide (H2S). Both of
      these probes behave aggression-induced emission (AIE) activity which fluoresces
      in the red region with a large Stokes shift. They exhibit rapid response to H2S
      with enormous colorimetric and ratiometric fluorescent changes. They are readily
      employed for assessing intracellular H2S levels.

PMID- 29579713
TI  - Mesoscale connectomics.
AB  - Brain cells communicate with one another via local and long-range synaptic
      connections. Structural connectivity is the foundation for neural function. Brain
      wide connectivity can be described at macroscopic, mesoscopic and microscopic
      levels. The mesoscale connectome represents connections between neuronal types
      across different brain regions. Building a mesoscale connectome requires a
      detailed understanding of the cell type composition of different brain regions
      and the patterns of inputs and outputs that each of these cell types receives and
      forms, respectively. In this review, I discuss historical and contemporary
      tracing techniques in both anterograde and retrograde directions to map the input
      and output connections at population and individual cell levels, as well as
      imaging and network analysis approaches to build mesoscale connectomes for
      mammalian brains.

PMID- 29579716
TI  - Special feature of kinetics of ZcE isomerization of beta-N-methylaminovinyl
      trifluoromethyl ketone in Ar matrix exposed to UV radiation and spontaneous E?Z
      isomerization of alpha-methyl-beta-N-methylaminovinyl trifluoromethyl ketone.
AB  - Although it is well known that reactivity of alpha,beta-unsaturated
      enaminoketones is closely associated with spatial and electronic structure but
      until now little attention was devoted to quantitative investigation of
      interconversion of different stereoisomeric forms of enaminoketones. In present
      work we studied peculiarities of kinetics of Z?E isomerization of enaminoketone 4
      (N-methylamino)-1,1,1-trifluorobut-3-en-2-one F3C-COCHCHNH(CH3) (1) in Ar-matrix
      exposed to UV-radiation (lambda=340nm) with IR Fourier and 2D correlation
      spectroscopy and we found that Z-s-Z-s-trans isomer transforms primarily into two
      E-isomers, E-s-E-s-trans and E-s-Z-s-trans which further turn into the E-s-E-s
      cis and E-s-Z-s-cis conformers all interconversion rate constants being
      comparable in magnitude. Along with this process long-term exposure to the UV
      radiation results in proton transfer from nitrogen of methylamino group to
      carbonyl oxygen with simultaneous isomerization of 'cyclic' iminoenol form into
      'linear'one. In solution of enaminoketone 4-(N-methylamino)-1,1,1-trifluoro-3
      methylbut-3-en-2-one F3C-CO-C(CH3)CH-NH(CH3) (2) we observed reversed process,
      namely, spontaneous interconversion of the E-s-E-s-trans and E-s-Z-s-trans
      conformers into the Z-s-Z-trans isomer. It was found that rate constants of the
      dimeric forms of the E-s-E-s-trans and E-s-Z-s-trans conformers are higher than
      those of the monomers and are independent on total enaminoketone concentration.
      Addition of highly polar HMPA promotes proton transfer from nitrogen to oxygen in
      the Z-s-Z-s-trans isomer of 2 with subsequent isomerization into the linear imino
      enol product but the rate constant of this transformation is ten-fold smaller
      than that for 1 in the Ar matrix exposed to UV radiation.

PMID- 29579715
TI  - Blue emitting copper nanoclusters as colorimetric and fluorescent probe for the
      selective detection of bilirubin.
AB  - Hurdles to develop point of care diagnostic methods restrict the translation of
      progress in the health care sector from bench side to bedside. In this article a
      simple, cost effective fluorescent as well as colorimetric nanosensor was
      developed for the early and easy detection of hyperbilirubinemia. A stable, water
      soluble bovine serum albumin stabilised copper nanocluster (BSA CuNC) was used as
      the fluorescent probe which exhibited strong blue emission (404nm) upon 330nm
      excitation. The fluorescence of the BSA CuNC can be effectively quenched by the
      addition of bilirubin by the formation of copper-bilirubin complex. Meanwhile the
      copper-bilirubin complex resulted in an observable colour change from pale violet
      to green facilitating colorimetric detection. The prepared sensor displayed good
      selectivity and sensitivity over other co-existing molecules, and can be used for
      quantifying bilirubin with a detection limit down to 257fM. Additionally, the as
      prepared probe was coated on a paper strip to develop a portable paper strip
      sensor of bilirubin. Moreover, the method was successfully applied in real sample
      analysis and obtained promising result.

PMID- 29579717
TI  - Pseudoprogression and hyperprogression after checkpoint blockade.
AB  - Immune checkpoint inhibitors appear to be one of the most promising
      immunotherapies with significant clinical benefits and durable responses in
      multiple tumor types. A heterogeneity of responses appears in patients receiving
      checkpoint blockade, including pseudoprogression where the tumor burden or number
      of tumor lesions increases initially before decreasing. Another special response
      observed after checkpoint blockade is hyperprogression, a phenomenon reflecting a
      very rapid tumor progression following immunotherapy, suggesting that checkpoint
      blockade could impact detrimentally on a small subset of patients. As
      immunotherapeutics, especially anti-PD-1/PD-L1 agents, become more widely
      available, evaluating the efficacy of these novel drugs poses a major challenge
      to clinicians, who aim to avoid either premature withdrawal of the treatment or
      prolonging ineffective treatment. Although the mechanism and recognition of
      pseudoprogression have gradually come to light, the incidence, basis,
      identification and predictive biomarkers of hyperprogression have been largely
      unknown, and this review documents the existing research findings and points out
      the areas where further studies are badly needed.

PMID- 29579718
TI  - Post-feeding activity of Lucilia sericata (Diptera: Calliphoridae) on common
      domestic indoor surfaces and its effect on development.
AB  - Developmental data of forensically important blowflies used by entomologists to
      estimate minimum post mortem interval (mPMI) are established under controlled
      laboratory conditions for various temperature ranges throughout the stages of
      egg, 1st-3rd instar, puparia, and adult fly emergence. However, environmental
      conditions may influence the patterns of development and behaviour of blowflies,
      potentially impacting on these established development rates. Previous studies
      investigating indoor colonisation have focused on the delay to oviposition, with
      behaviour during the post-feeding phase in this setting often overlooked. The
      environment in which third instar larvae disperse when searching for a
      pupariation site may vary drastically at both outdoor and indoor scenarios,
      influencing the activity and distance travelled during this phase and possibly
      affecting developmental rates. This study investigated the effect of eight common
      domestic indoor surfaces on dispersal time, distance travelled, and behaviour of
      post-feeding Lucilia sericata as well as any resulting variation in development.
      It was found that pupariation and puparia length within a pupariation medium of
      sawdust (often used in laboratory settings) produced comparable results with that
      of carpeted environments (those deemed to be 'enclosed'). Non-carpeted
      environments (those which were 'exposed') produced a delay to pupariation likely
      due to increased activity and energy expenditure in searching for pupariation
      sites which enabled burial. In addition, the observed speed of travel during
      dispersal was seen via time lapse photography to be greater within 'exposed'
      conditions. Larvae which dispersed upon burnt laminate flooring were observed to
      travel faster than in all other conditions and showed the only significant
      variation (P=0.04) in the day of emergence in comparison to the control condition
      of sawdust. This study has demonstrated that wandering phase activity is affected
      by the environmental surface which has potential implications for estimating both
      the distance travelled by dispersing larvae in indoor conditions and with further
      research, may be a consideration in mPMI calculations.

PMID- 29579720
TI  - Biomechanical analysis of the durability of a modified S1 vertebrae
      transpedicular screws insertion technique.
AB  - BACKGROUND: One of the most important elements of the transpedicular screw
      implantation technique, which enables a strong screw-bone interface, is the
      precise choice of the site of screw insertion and the screw's trajectory. Due to
      the complex biomechanics of the lumbosacral interface and different shape of the
      sacrum, fixation of this segment remains a challenge for surgeons. Because of
      this, Kubaszewski et al. proposed a modified technique in which the entry point
      for screw insertion in the S1 vertebra is changed. METHODS: Six human cadaver
      specimens of the S1 vertebrae were examined. Two transpedicular screws were
      inserted into the body of each examined vertebra using two implantation methods
      with different screw entry points and trajectories. The screws were subjected to
      cyclic preloading, followed by the pull-out test. The ultimate pull-out force,
      displacement, stiffness, and failure energy were measured. FINDINGS: The average
      pull-out force obtained for the standard method of implantation was 498 N (SD
      201), whereas for the modified technique, it was 1308 N (SD 581). Displacement of
      the inserted screws in the new method was 36% higher than in the case of the
      standard method. This method is also characterized by the greater stiffness of
      the obtained interface and greater failure energy than the normally used
      technique. INTERPRETATION: The obtained results demonstrate that the use of the
      new technique of implantation significantly increases the strength of the
      obtained screw-bone interface. It should also increase the success rate of the
      performed fixations and increase the safety of such fixations in clinical
      practice.

PMID- 29579721
TI  - The influence of isolated femur and tibia rotations on patella cartilage stress:
      a sensitivity analysis.
AB  - BACKGROUND: To determine the influence of femur and tibia rotations in the
      transverse and frontal planes on patella cartilage stress. METHODS: Patella
      cartilage stress profiles of six healthy females were obtained during a squatting
      task using subject-specific finite element models of the patellofemoral joint (45
      degrees  of knee flexion). Input parameters for the finite element model included
      joint geometry, quadriceps muscle forces, and weight-bearing patellofemoral joint
      kinematics. The femur and tibia of each model were then rotated to 2 degrees , 4
      degrees , 6 degrees , 8 degrees , and 10 degrees  along their respective axes
      beyond that of the natural degree of rotation in weight-bearing. The process was
      repeated for internal rotation, external rotation, adduction, and abduction.
      Quasi-static loading simulations were performed to quantify average patella
      cartilage stress. FINDINGS: Incremental femur internal rotation beyond that of
      the natural rotation resulted in progressively greater patella cartilage stress
      (41-77%), whereas incremental tibia internal rotation resulted in a decrease in
      patella cartilage stress (7-10%). Femur and tibia external rotation resulted in a
      mild increase in patella cartilage stress, but only at 10 degrees  (9%).
      Incremental femur adduction resulted in an increase in patella cartilage stress,
      but only at 10 degrees  (43%). Femur abduction and frontal plane tibia rotation
      in either direction had no influence on patella cartilage stress. INTERPRETATION:
      Femur internal rotation and adduction resulted in the greatest increases in
      patella cartilage stress. In contrast, tibia rotations in the transverse and
      frontal planes had minimal to no influence on patella cartilage stress. These
      results emphasize the need for clinicians to identify and correct faulty hip
      kinematics in persons with PFP.

PMID- 29579719
TI  - Copper accumulation in senescent cells: Interplay between copper transporters and
      impaired autophagy.
AB  - Cellular senescence is characterized by irreversible growth arrest incurred
      through either replicative exhaustion or by pro-oncogenic cellular stressors
      (radioactivity, oxidative stress, oncogenic activation). The enrichment of
      senescent cells in tissues with age has been associated with tissue
      dyshomeostasis and age-related pathologies including cancers, neurodegenerative
      disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g.
      diabetes). We identified copper accumulation as being a universal feature of
      senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial
      cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs
      was accompanied by elevated levels of high-affinity copper uptake protein 1
      (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export)
      and enhanced antioxidant defence reflected by elevated levels of glutathione
      (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of
      intracellular copper were further increased in senescent MEFs cultured in copper
      supplemented medium and in senescent Mottled Brindled (Mobr) MEFs lacking
      functional Atp7a. Finally, we demonstrated that the restoration/preservation of
      autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment
      correlated with attenuation of copper accumulation in these cells despite a
      further decrease in Atp7a levels. This study for the first time establishes a
      link between Atp7a and the autophagic-lysosomal pathway, and a requirement for
      both to effect efficient copper export. Such a connection between cellular
      autophagy and copper homeostasis is significant, as both have emerged as
      important facets of age-associated degenerative disease.

PMID- 29579722
TI  - Attachment insecurity and power regulation in intimate relationships.
AB  - Power and dependence are fundamental to the development of attachment insecurity
      and attachment insecurity is central in defining different ways people regulate
      power. This paper applies an integrated power and attachment perspective to
      advance understanding of the diverse ways people attempt to negotiate dependence
      and power in adult relationships. The paper demonstrates how: (1) power is
      integral to the concerns and goals underlying attachment avoidance and anxiety,
      (2) the situations that activate attachment strategies represent specific power
      relevant concerns and goals, (3) the reactions associated with avoidance and
      anxiety reflect distinct strategies to regulate dependence and control, and (4)
      partners counter with their own power regulation attempts. The integrative model
      presented generates new insights into both power and attachment dynamics.

PMID- 29579723
TI  - Attachment and eating disorders: a research update.
AB  - Prominent models of eating disorders tend to focus on cognitive and behavioral
      features, but tend not to consider important developmental issues related to
      affect regulation, interpersonal style, self concept, and mentalization-all of
      which are well conceptualized within attachment theory. Higher levels of
      attachment insecurity across diagnoses are related to greater eating disorder
      symptoms. Low parental care and early trauma may lead to attachment insecurity
      that then might lead to greater eating disorder symptoms. The association between
      insecure attachment and eating disorder severity is likely mediated by affect
      dysregulation and perfectionism. Recent research using the Adult Attachment
      Interview highlights the importance of reflective functioning in predicting
      treatment response and therapeutic processes, and on the utility of therapies
      that increase mentalization.

PMID- 29579724
TI  - Associations between opioid and nicotine dependence in nationally representative
      samples of United States adult daily smokers.
AB  - INTRODUCTION: Smoking prevalence among adults with opioid dependence far exceeds
      that of the general population, and cessation outcomes in this group are one
      fourth that of smokers without a substance use disorder. Understanding the
      reasons underlying these poor outcomes is critical for developing more effective
      smoking interventions in this group. Elevated baseline severity of nicotine
      dependence is associated with lower rates of smoking cessation over time. We
      examined whether nicotine dependence severity among smokers may vary as a
      function of opioid dependence status using nationally representative samples of
      adult smokers. METHODS: Data were derived from multiple years of the National
      Survey on Drug Use and Health (NSDUH, 2006-2014; n = 58,971). Nicotine dependence
      was measured by the Nicotine Dependence Syndrome Scale (NDSS) and the first item
      (i.e., time to first cigarette) of the Fagerstrom Test for Nicotine Dependence
      (FTND). Opioid dependence was assessed using the Diagnostic and Statistical
      Manual of Mental Disorders criteria. RESULTS: Opioid-dependent smokers exhibited
      greater severity of nicotine dependence compared to non-opioid dependent smokers,
      as evidenced by higher mean NDSS scores (p < 0.05). On both NDSS and FTND
      measures of nicotine dependence, opioid-dependent smokers were also approximately
      twice as likely to be dependent on nicotine than those not dependent on opioids
      (p's < 0.05). CONCLUSIONS: Opioid dependence is associated with increased
      severity and prevalence of nicotine dependence among smokers. Considering the
      disproportionate societal and economic burdens of smoking and smoking-related
      consequences in this vulnerable population, continued investigations are needed
      to better understand opioid-dependent individuals' poor cessation outcomes.

PMID- 29579725
TI  - Addressing discordant quantitative urine buprenorphine and norbuprenorphine
      levels: Case examples in opioid use disorder.
AB  - INTRODUCTION: Urine adulteration is a concern among patients treated for opioid
      use disorder. Quantitative urine testing for buprenorphine (B) and
      norbuprenorphine (NB), and the appropriate interpretation of B and NB levels, can
      facilitate constructive conversations with patients that may lead to
      modifications in the treatment plan, and strengthening of the patient-provider
      relationship. CASE SUMMARY: Three cases are presented in which discordant urine B
      and NB levels were recognized. Each patient was submerging buprenorphine/naloxone
      strips in their urine to mask ongoing illicit drug use. The authors used an
      approach to addressing intentional adulteration of urine samples that adheres to
      the principles of harm-reduction, the centrality of the patient-provider
      relationship, and the acknowledgment that ongoing illicit drug use and subsequent
      dishonesty about disclosure may be common among persons with substance use
      disorders. Each of the three patients ultimately endorsed diluting their urine,
      which allowed for strengthening of the patient-provider relationship and
      modifications to their treatment plans. Two of the three patients stabilized and
      achieved abstinence, while the third was eventually referred to a methadone
      treatment program. CONCLUSION: Providers should routinely monitor B and NB
      levels, rather than qualitative screening alone, and discordant levels should
      elicit a timely conversation with the patient. The authors use of a nonjudgmental
      approach to address urine adulteration, including giving patients an opportunity
      to reflect on potential solutions, has been effective at helping patients and
      providers to reestablish a therapeutic alliance and maintain retention in
      treatment.

PMID- 29579726
TI  - Significance, evolution and recent advances in adsorption technology, materials
      and processes for desalination, water softening and salt removal.
AB  - Desalination and softening of sea, brackish, and ground water are becoming
      increasingly important solutions to overcome water shortage challenges. Various
      technologies have been developed for salt removal from water resources including
      multi-stage flash, multi-effect distillation, ion exchange, reverse osmosis,
      nanofiltration, electrodialysis, as well as adsorption. Recently, removal of
      solutes by adsorption onto selective adsorbents has shown promising perspectives.
      Different types of adsorbents such as zeolites, carbon nanotubes (CNTs),
      activated carbons, graphenes, magnetic adsorbents, and low-cost adsorbents
      (natural materials, industrial by-products and wastes, bio-sorbents, and
      biopolymer) have been synthesized and examined for salt removal from aqueous
      solutions. It is obvious from literature that the existing adsorbents have good
      potentials for desalination and water softening. Besides, nano-adsorbents have
      desirable surface area and adsorption capacity, though are not found at
      economically viable prices and still have challenges in recovery and reuse. On
      the other hand, natural and modified adsorbents seem to be efficient alternatives
      for this application compared to other types of adsorbents due to their
      availability and low cost. Some novel adsorbents are also emerging. Generally,
      there are a few issues such as low selectivity and adsorption capacity, process
      efficiency, complexity in preparation or synthesis, and problems associated to
      recovery and reuse that require considerable improvements in research and process
      development. Moreover, large-scale applications of sorbents and their practical
      utility need to be evaluated for possible commercialization and scale up.

PMID- 29579727
TI  - Protected area effectiveness against land development in Spain.
AB  - Land use-land cover (LULC) changes towards artificial covers are one of the main
      global threats to biodiversity conservation. In this comprehensive study, we
      tested a number of methodological and research hypotheses, and a new covariate
      control technique in order to address common protected area (PA) assessment
      issues and accurately assess whether different PA networks have had an effect at
      preventing development of artificial LULCs in Spain, a highly biodiverse country
      that has experienced massive socioeconomic transformations in the past two
      decades. We used digital census data for four PA networks designated between 1990
      and 2000: Nature Reserves (NRs), Nature Parks (NPs), Sites of Community
      Importance (SCIs) and Special Protection Areas (SPAs). We analysed the effect of
      explanatory variables on the ecological effectiveness of protected polygons
      (PPs): Legislation stringency, cummulative legal designations, management, size,
      age and bio-physical characteristics. A multiple Before-After-Control-Impact
      (BACI) semi-experimental research design was used whereby artificial land cover
      increase (ALCI) and proportional artificial land cover increase (PALCI) results
      were compared inside and outside PAs, using 1 km and 5 km buffer areas
      surrounding PAs as controls. LULC data were retrieved from Corine Land Cover
      (CLC) 1990 and 2006 data. Results from three spatial-statistical models using
      progressively restrictive criteria to select control areas increasingly more
      accurate and similar to the assessed PPs were compared. PAs were a generally
      effective territorial policy to prevent land development in Spain. NRs were the
      most effective PA category, with no new artificial land covers in the assessed
      period, although exact causality could not be attributed due to legal overlaps.
      SPAs were the least effective category, with worse ALCI data than their control
      areas. Legal protection was effective against land development, which was
      influenced by most bio-physical variables. However, cumulative legal designations
      and PA management did not seem to influence land development. The spatial
      statistical technique used to make cases and control environmentally similar did
      not produce consistent outcomes and should be refined.

PMID- 29579728
TI  - Wastewater post-treatment for simultaneous ammonium removal and elemental sulfur
      recovery using a novel horizontal mixed aerobic-anoxic fixed-bed reactor
      configuration.
AB  - A novel horizontal mixed anoxic-aerobic fixed-bed reactor configuration based on
      nitrification coupled with autotrophic denitrification using hydrogen sulfide as
      an electron donor was developed. The nitrification removal efficiency (RE)
      reached values greater than 99% but was slightly affected by the accumulation of
      dissolved sulfur species in the liquid phase. The denitrification RE reached 99%
      with a H2S inlet load of 28.6 g S m-3 h-1, although the use of aluminum
      polychloride (PAC) as a sulfur coagulant in the anoxic zone affected the
      buffering capacity of the system and resulted in a decrease in the RE. The
      performance of the reactor was primarily affected by the buffering capacity of
      the system, and this effect could be controlled with an increase in the NaHCO3
      concentration. The recovery of biogenic elemental sulfur was possible using PAC
      as a coagulant, although the solid collected at the bottom of the settling tank
      contained only 1.5% S0.

PMID- 29579729
TI  - Antibacterial activity on superhydrophobic titania nanotube arrays.
AB  - Bacterial infections are a serious issue for many implanted medical devices.
      Infections occur when bacteria colonize the surface of an implant and form a
      biofilm, a barrier which protects the bacterial colony from antibiotic
      treatments. Further, the anti-bacterial treatments must also be tailored to the
      specific bacteria that is causing the infection. The inherent protection of
      bacteria in the biofilm, differences in bacteria species (gram-positive vs. gram
      negative), and the rise of antibiotic-resistant strains of bacteria makes device
      acquired infections difficult to treat. Recent research has focused on reducing
      biofilm formation on medical devices by modifying implant surfaces. Proposed
      methods have included antibacterial surface coatings, release of antibacterial
      drugs from surfaces, and materials which promote the adhesion of non-pathogenic
      bacteria. However, no approach has proven successful in repelling both gram
      positive and gram-negative bacteria. In this study, we have evaluated the ability
      of superhydrophobic surfaces to reduce bacteria adhesion regardless of whether
      the bacteria are gram-positive or gram-negative. Although superhydrophobic
      surfaces did not repel bacteria completely, they had minimal bacteria attached
      after 24 h and more importantly no biofilm formation was observed.

PMID- 29579730
TI  - Emotion regulation in Schizophrenia: A comparison between implicit (EEG and
      fNIRS) and explicit (valence) measures: Preliminary observations.

PMID- 29579731
TI  - Conceptualizing plant systems evolution.
AB  - Organisms inhabiting extreme environments are emerging models in systems
      evolution, enabling us to identify the molecular alterations effecting major
      phenotypic divergence through comparative approaches. Here I discuss possible
      physiological mechanisms underlying evolutionary adaptations to extreme
      environments both theoretically and in relation to experimental observations.
      Reasoning leads me to the 'conserved steady-state' hypothesis of evolutionary
      adaptation: Between closely related plants adapted to differently composed soils,
      the homeostatically controlled steady-state set point cytosolic (buffered)
      concentrations of mineral ions are conserved. Subsequently, I compare molecular
      alterations expected to contribute to physiological adaptations with our present
      knowledge. Key roles of enhanced gene product dosage in plant evolutionary
      adaptations question the widespread stimulus response-centric paradigm. As a
      broader implication, co-regulation networks can lack decisive functional network
      elements. With this article, I hope to stimulate a discussion across research
      fields and provide an initial conceptual framework for future experimental
      testing and for quantitative modelling.

PMID- 29579732
TI  - Development, validation and utilization of a highly sensitive LC-MS/MS method for
      quantification of levonorgestrel released from a subdermal implant in human
      plasma.
AB  - Levonorgestrel (LNG) is a synthetic progestin that is available in oral
      contraceptive tablets, a subdermal implant, and an intrauterine system for
      contraception. LNG pharmacokinetics are a pivotal determinant of contraceptive
      efficacy and essential in assessing drug-drug interactions influencing LNG
      exposure following different routes of LNG administration. A highly sensitive LC
      MS/MS method was developed and validated to quantify levonorgestrel in human
      plasma. Liquid-liquid extraction was utilized with a sample volume of 500 MUL to
      extract levonorgestrel from plasma. Chromatographic separation of LNG was
      achieved with a FortisTM C18 (3 MUm: 100 mm * 2.1 mm) reverse phase analytical
      column. The mobile phases consisted of de-ionized water plus 0.1% NH4OH
      (100:0.1%, v/v) (A), and methanol plus 0.1% NH4OH (100:0.1%, v/v) (B) delivered
      as a gradient at a flow rate of 400 MUL/min. Detection of LNG and internal
      standard (D-(-)-norgestrel-d7) was achieved using positive polarity mode
      monitoring at 313.2-245.2 amu and 320.1-251.2 amu, respectively. The assay was
      linear over the calibration range of 49.6 to 1500 pg/mL. This method was used to
      quantify plasma LNG released by subdermal implant in support of a drug
      interaction study among women with HIV receiving efavirenz- or nevirapine-based
      antiretroviral therapy.

PMID- 29579733
TI  - Optimization of a two-dimensional liquid chromatography-supercritical fluid
      chromatography-mass spectrometry (2D-LC-SFS-MS) system to assess "in-vivo" inter
      conversion of chiral drug molecules.
AB  - Enantioselective analysis is an essential requirement during the pharmaceutical
      development of chiral drug molecules. In pre-clinical and clinical studies, the
      Food and Drug Administration (FDA) mandates the assessment of "in vivo" inter
      conversion of chiral drugs to determine their physiological effects. In-vivo
      analysis of the active pharmaceutical ingredient (API) and its potential
      metabolites could be quite challenging due to their low abundance (ng/mL levels)
      and matrix interferences. Therefore, highly selective and sensitive analytical
      techniques are required to separate the API and its metabolites from the matrix
      components and one another. Additionally, for chiral APIs, further analytical
      separation is required to resolve the API and its potential metabolites from
      their corresponding enantiomers. In this work, we demonstrate the optimization of
      our previously designed two-dimensional liquid chromatography-supercritical fluid
      chromatography-mass spectrometry (2D-LC-SFC -MS) system to achieve 10 ng/mL
      detection limit [1]. The first LC dimension, used as a desalting step, could
      efficiently separate the API from its potential metabolites and matrix
      components. The API and its metabolites were then trapped/focused on small
      trapping columns and transferred onto the second SFC dimension for chiral
      separation. Detection can be achieved by ultra-violet (UV) or MS detection.
      Different system parameters such as column dimensions, transfer volumes, trapping
      column stationary phase, system tubing internal diameter (i.d.), and detection
      techniques, were optimized to enhance the sensitivity of the 2D-LC-SFC-MS system.
      The limit of detection was determined to be 10 ng/mL. An application is described
      where a mouse hepatocyte treated sample was analyzed using the optimized 2D-LC
      SFC-MS system with successful assessment of the ratio of API to its metabolite
      (1D-LC), as well as the corresponding enantiomeric excess values (% e.e.) of each
      (2D-SFC).

PMID- 29579734
TI  - Major signal suppression from metal ion clusters in SFC/ESI-MS - Cause and
      effects.
AB  - The widening application area of SFC-MS with polar analytes and water-containing
      samples facilitates the use of quick and simple sample preparation techniques
      such as "dilute and shoot" and protein precipitation. This has also introduced
      new polar interfering components such as alkali metal ions naturally abundant in
      e.g. blood plasma and urine, which have shown to be retained using screening
      conditions in SFC/ESI-TOF-MS and causing areas of major ion suppression. Analytes
      co-eluting with these clusters will have a decreased signal intensity, which
      might have a major effect on both quantification and identification. When
      investigating the composition of the alkali metal clusters using accurate mass
      and isotopic pattern, it could be concluded that they were previously not
      described in the literature. Using NaCl and KCl standards and different
      chromatographic conditions, varying e.g. column and modifier, the clusters proved
      to be formed from the alkali metal ions in combination with the alcohol modifier
      and make-up solvent. Their compositions were [(XOCH3)n + X]+, [(XOH)n + X]+,
      [(X2CO3)n + X]+ and [(XOOCOCH3)n + X]+ for X = Na+ or K+ in ESI+. In ESI-, the
      clusters depended more on modifier, with [(XCl)n + Cl]- and [(XOCH3)n + OCH3]-
      mainly formed in pure methanol and [(XOOCH)n + OOCH]- when 20 mM NH4Fa was added.
      To prevent the formation of the clusters by avoiding methanol as modifier might
      be difficult, as this is a widely used modifier providing good solubility when
      analyzing polar compounds in SFC. A sample preparation with e.g. LLE would remove
      the alkali ions, however also introducing a time consuming and discriminating
      step into the method. Since the alkali metal ions were retained and affected by
      chromatographic adjustments as e.g. mobile phase modifications, a way to avoid
      them could therefore be chromatographic tuning, when analyzing samples containing
      them.

PMID- 29579735
TI  - Variability between organs of proanthocyanidins in Geranium sylvaticum analyzed
      by off-line 2-dimensional HPLC-MS.
AB  - Proanthocyanidins have been characterized in the different organs of Geranium
      sylvaticum by using an off-line 2-dimensional chromatographic method. In the
      first dimension, proanthocyanidins were separated according to their increasing
      degree of polymerization by hydrophilic interaction liquid chromatography. In the
      second dimension, reversed-phase liquid chromatography was used to separate the
      same size isomers based on their hydrophobicity. Ultraviolet detection and high
      resolution electrospray ionization time-of-flight mass spectrometry were used for
      the identification and characterization of proanthocyanidins. The method was
      proven to be suitable for the analysis of plant organ fractions of G. sylvaticum
      that contained complex mixtures of phenolic compounds and proanthocyanidins from
      several classes. Procyanidins, prodelphinidins and mixed proanthocyanidins
      composed of both (epi)catechin and (epi)gallocatechin units including monomers,
      oligomers and polymers up to the degree of polymerization of 20 were identified.
      The type and size of proanthocyanidins varied between eight studied organs of G.
      sylvaticum. The 2-dimensional analysis revealed that each proanthocyanidin type
      occur in the equally complex isomeric pattern. The mean degree of polymerization
      of different proanthocyanidins in the eight plant organs of G. sylvaticum was 5
      and it varied only slightly between plant organs.

PMID- 29579737
TI  - A Facets Analysis of Analytic vs. Holistic Scoring of Identical Short Constructed
      Response Items: Different Outcomes and Their Implications for Scoring Rubric
      Development.
AB  - In scoring short constructed-response items it may be possible to apply different
      rubric types depending on the trait of achievement assessed. A rating scale and a
      partial credit Many-Facet Rasch Models (MFRM) were used to investigate whether
      levels-based (holistic) and hybrid (analytic) scoring rubrics functioned
      interchangeably when scoring short-response English reading comprehension test
      items. Whereas most research in similar contexts has focused solely on rater
      reliability, the use of MFRM in this study enabled examination of both the
      reliability and rating scale functioning aspects of scoring rubrics in parallel.
      It also enabled consideration of their effects on item and examinee parameters.
      This more comprehensive approach allowed the findings to be linked to general
      notions of rubric construct-relevance and score interpretation, and to
      demonstrate an approach to generating evidence for a more balanced consideration
      of advantages and disadvantages of each rubric in terms of both reliability and
      validity.

PMID- 29579736
TI  - Metformin reduces glucose intolerance caused by rapamycin treatment in
      genetically heterogeneous female mice.
AB  - The use of rapamycin to extend lifespan and delay age-related disease in mice is
      well-established despite its potential to impair glucose metabolism which is
      driven partially due to increased hepatic gluconeogenesis. We tested whether a
      combination therapeutic approach using rapamycin and metformin could diminish
      some of the known metabolic defects caused by rapamycin treatment in mice. In
      genetically heterogeneous HET3 mice, we found that chronic administration of
      encapsulated rapamycin by diet caused a measurable defect in glucose metabolism
      in both male and female mice as early as 1 month after treatment. In female mice,
      this defect was alleviated over time by simultaneous treatment with metformin,
      also by diet, such that females treated with both drugs where indistinguishable
      from control mice during glucose tolerance tests. While rapamycin-mediated
      glucose intolerance was unaffected by metformin in males, we found metformin
      prevented rapamycin-mediated reduction in insulin and leptin concentrations
      following 9 months of co-treatment. Recently, the Interventions Testing Program
      showed that mice treated with metformin and rapamycin live at least as long as
      those treated with rapamycin alone. Together, our data provide compelling
      evidence that the pro-longevity effects of rapamycin can be uncoupled from its
      detrimental effects on metabolism through combined therapeutic approaches.

PMID- 29579738
TI  - Q-Matrix Optimization Based on the Linear Logistic Test Model.
AB  - This study explored optimization of item-attribute matrices with the linear
      logistic test model (Fischer, 1973), with optimal models explaining more variance
      in item difficulty due to identified item attributes. Data were 8th-grade
      mathematics test item responses of two TIMSS 2007 booklets. The study
      investigated three categories of attributes (content, cognitive process, and
      comprehensive cognitive process) at two grain levels (larger, smaller) and also
      compared results with random attribute matrices. The proposed attributes
      accounted for most of the variance in item difficulty for two assessment booklets
      (81% and 65%). The variance explained by the content attributes was very small
      (13% to 31%), less than variance explained by the comprehensive cognitive process
      attributes which explained much more variance than the content and cognitive
      process attributes. The variances explained by the grain level were similar to
      each other. However, the attributes did not predict the item difficulties of two
      assessment booklets equally.

PMID- 29579739
TI  - Mapping a Data Modeling and Statistical Reasoning Learning Progression using
      Unidimensional and Multidimensional Item Response Models.
AB  - There are different ways to conceive and measure learning progressions. The
      approach used by the ADMSR project followed the "four building blocks" approach
      outlined by the Berkeley Evaluation and Assessment Research (BEAR) Center and the
      BEAR Assessment System. The final building block of this approach involves the
      application of a measurement model. This paper focuses on the application of
      unidimensional and multidimensional item response theory (IRT) measurement models
      to the data from the ADMSR project. Unidimensional IRT models are applied to aid
      in construct development and validation to see if the proposed theory of
      development presented by the construct map is supported by the results from an
      administration of the instrument. Multidimensional IRT measurement models are
      applied to examine the relationships between the seven constructs in the ADMSR
      learning progression. When applying the multidimensional model, specific links
      between levels of the constructs are analyzed across constructs after the
      application of a technique to align the seven dimensions.

PMID- 29579740
TI  - Psychometric Properties of the Classroom Assessment Scoring System (Pre-K):
      Implications for Measuring Interaction Quality in Diverse Early Childhood
      Settings.
AB  - The Classroom Assessment Scoring System (CLASS) is an observational instrument
      assessing the nature of everyday interactions in educational settings. The
      instrument has strong theoretical groundings; however, prior empirical validation
      of the CLASS has exposed some psychometric weaknesses. Further the instrument has
      not been the subject of psychometric analysis at the indicator level. Using a
      large dataset including observations of 993 Australian classrooms, confirmatory
      factor analysis is used to replicate findings from the few existing validation
      studies. Item response modelling is used to examine individual indicator
      behaviour. Latent growth models are used to produce new findings about estimating
      factor scores. Findings show that the CLASS exhibits stable psychometric
      properties within classrooms over repeated observations. Model fit is improved
      and factor scores are more reliable when the repeated-observations made in
      administering the CLASS are accounted for statistically. It is recommended that
      researchers enforce a fixed number of repeated observations to minimise bias.

PMID- 29579741
TI  - Ordered Partition Model for Confidence Marking Modeling.
AB  - Confidence marking is increasingly used in multiple choice testing situations,
      but when the Rasch measurement model is applied to the data, only the binary data
      is used, discarding the information given by the confidence marking. This study
      shows how Wilson's ordered partition model (OPM), a member of the Rasch family of
      models, can be used to model the confidence information. The result is a model
      which is in strict relation to the binary Rasch model, since the Rasch ICC's are
      "split" into a set of curves each representing a confidence level. The new model
      provides a set of item parameters that map the probability of being in each
      confidence level in relation to the test-taker's ability. The study provides a
      powerful diagnostic tool to assess item difficulty, overconfidence or misuse of
      confidence levels but also the fact that a question is particularly tricky or
      creates a lot of doubt.

PMID- 29579742
TI  - Development of an Item Bank for the Assessment of Knowledge on Biology in
      Argentine University Students.
AB  - The calibration of item banks provides the basis for computerized adaptive
      testing that ensures high diagnostic precision and minimizes participants' test
      burden. This study aims to develop a bank of items to measure the level of
      Knowledge on Biology using the Rasch model. The sample consisted of 1219
      participants that studied in different faculties of the National University of
      Cordoba (mean age = 21.85 years, SD = 4.66; 66.9% are women). The items were
      organized in different forms and into separate subtests, with some common items
      across subtests. The students were told they had to answer 60 questions of
      knowledge on biology. Evaluation of Rasch model fit (Zstd >|2.0|), differential
      item functioning, dimensionality, local independence, item and person separation
      (>2.0), and reliability (>.80) resulted in a bank of 180 items with good
      psychometric properties. The bank provides items with a wide range of content
      coverage and may serve as a sound basis for computerized adaptive testing
      applications. The contribution of this work is significant in the field of
      educational assessment in Argentina.

PMID- 29579743
TI  - Room-temperature nine-um-wavelength photodetectors and GHz-frequency heterodyne
      receivers.
AB  - Room-temperature operation is essential for any optoelectronics technology that
      aims to provide low-cost, compact systems for widespread applications. A recent
      technological advance in this direction is bolometric detection for thermal
      imaging, which has achieved relatively high sensitivity and video rates (about 60
      hertz) at room temperature. However, owing to thermally induced dark current,
      room-temperature operation is still a great challenge for semiconductor
      photodetectors targeting the wavelength band between 8 and 12 micrometres, and
      all relevant applications, such as imaging, environmental remote sensing and
      laser-based free-space communication, have been realized at low temperatures. For
      these devices, high sensitivity and high speed have never been compatible with
      high-temperature operation. Here we show that a long-wavelength (nine
      micrometres) infrared quantum-well photodetector fabricated from a metamaterial
      made of sub-wavelength metallic resonators exhibits strongly enhanced performance
      with respect to the state of the art up to room temperature. This occurs because
      the photonic collection area of each resonator is much larger than its electrical
      area, thus substantially reducing the dark current of the device. Furthermore, we
      show that our photonic architecture overcomes intrinsic limitations of the
      material, such as the drop of the electronic drift velocity with temperature,
      which constrains conventional geometries at cryogenic operation. Finally, the
      reduced physical area of the device and its increased responsivity allow us to
      take advantage of the intrinsic high-frequency response of the quantum detector
      at room temperature. By mixing the frequencies of two quantum-cascade lasers on
      the detector, which acts as a heterodyne receiver, we have measured a high
      frequency signal, above four gigahertz (GHz). Therefore, these wide-band uncooled
      detectors could benefit technologies such as high-speed (gigabits per second)
      multichannel coherent data transfer and high-precision molecular spectroscopy.

PMID- 29579744
TI  - Antimicrobial Essential Oil Combinations to Combat Foot Odour.
AB  - Foot odour (bromodosis) is an embarrassing and perplexing condition mostly caused
      by bacteria of the Brevibacterium species. Essential oils are a credible option
      as an affordable treatment of odour and contribute towards antimicrobial
      efficacy. Therefore, this study sets out to investigate the antimicrobial
      activity of essential oil combinations against odour-causing bacteria. The broth
      microdilution method was used to investigate the antimicrobial activity of 119
      essential oil combinations, and the fractional inhibitory index was calculated to
      determine the interactive profile. Combinations that resulted in synergy in 1 : 1
      ratios were further evaluated in different concentrations, and isobolograms were
      plotted to determine the influence of the ratio on overall activity. Numerous
      combinations could be identified as having synergistic interactions against the
      Brevibacterium spp. and no antagonism was observed. The combination of Juniperus
      virginiana (juniper) and Styrax benzoin (benzoin) demonstrated synergy against
      all three Brevibacterium spp. tested and J. virginiana was the essential oil
      responsible for the majority of the synergistic interactions. The results
      reported here confirm the promising potential of the majority of these oils and
      selected combinations in treating and controlling bromodosis.

PMID- 29579745
TI  - Free-Flap Lower Extremity Reconstruction: A Cohort Study and Meta-Analysis of
      Flap Anastomotic Outcomes between Perforator and Nonperforator Flaps.
AB  - INTRODUCTION:  Free-flap outcomes in lower extremity reconstruction carry the
      lowest anastomotic success rates compared with other anatomical sites. Despite
      their advantages over traditional nonperforator flaps, free perforator flaps have
      only recently become established in this area due to the additional challenges
      faced. It is therefore crucial to assess the anastomotic outcomes of perforator
      and nonperforator free flaps. METHODS:  We performed a single-center
      retrospective cohort study and combined this with a meta-analysis of the relevant
      literature. We evaluated three flap anastomotic outcomes: reexploration,
      operative salvage, and flap failure rates. RESULTS:  Between January 2010 and
      June 2015, our center managed 161 patients who underwent lower extremity free
      flap reconstruction, which included 76 perforator flaps and 85 nonperforator
      flaps. The perforator flaps had higher reexploration rates compared with the
      nonperforator flaps, but this was not statistically significant (18.4 and 10.6%;
      p = 0.18). Perforator flaps had a higher flap salvage rate but were not
      statistically significant (78.6 and 22.2%; p = 0.374). Lastly, although not
      statistically significant, perforator flaps had a lower rate of complete failure
      due to anastomotic complications (3.9 and 8.2%; p = 0.336). The meta-analysis
      included 12 studies (inclusive of the index study) and found no statistical
      difference in all three outcomes. CONCLUSION:  Our meta-analysis is the first
      reported study and serves as an indication that free perforator flaps in lower
      extremity are as reliable as their traditional nonperforator counterparts. This
      does come with the prerequisite appreciation of the anatomical variations, the
      delicate handling of these flaps, and a low threshold for reexploration.

PMID- 29579746
TI  - Good Agreement Between Transabdominal and Endoscopic Ultrasound of the Pancreas
      in Chronic Pancreatitis.
AB  - PURPOSE:  We aimed to evaluate the agreement of single criteria and dedicated
      scores from transabdominal ultrasound of the pancreas (US) compared to standards
      by endoscopic ultrasound (EUS) and computed tomography (CT). MATERIALS AND
      METHODS:  In this observational cohort study performed in a tertiary care center,
      US and EUS were performed in 110 patients referred for suspected CP. Based on the
      Mayo score, 52 patients were diagnosed with CP. The sonographic findings obtained
      by both methods were registered. The number of criteria was counted and scored
      according to the Rosemont score. RESULTS:  Agreement between the number of
      detected US and EUS criteria was substantial (ICC = 0.74 [0.61 - 0.83]. Adding
      Rosemont weighting improved the agreement (ICC = 0.88 [0.81 - 0.92]). Regarding
      individual criteria, the agreement was substantial for the detection of
      calcifications (kappa = 0.86) and moderate for cysts and irregular or dilated
      pancreatic duct (kappa = 0.42 - 0.58). Agreement for the other criteria was
      poorer (kappa<= 0.40). The diagnostic performance indices [95 % CI] of US for
      diagnosing CP (using Mayo score as reference standard) were for the unweighted
      score: Sensitivity: 0.65 [0.51 - 0.78], specificity: 0.97 [0.87 - 1.00]; and for
      Rosemont score: Sensitivity: 0.75 [0.61 - 0.86], specificity: 0.95 [0.83 - 0.99].
      CONCLUSION:  The agreement between US and EUS for the unweighted and weighted
      scores was substantial. For the features calcifications, cysts and main
      pancreatic duct (MPD) changes, agreement was moderate to substantial. For the
      other detected US criteria, the agreement with EUS was too poor to be clinically
      relevant.

PMID- 29579747
TI  - [Posterior Impingement Syndrome of the Ankle Joint].

PMID- 29579748
TI  - ?

PMID- 29579750
TI  - ?

PMID- 29579749
TI  - ?

PMID- 29579751
TI  - ?

PMID- 29579752
TI  - ?

PMID- 29579753
TI  - ?

PMID- 29579754
TI  - ?

PMID- 29579755
TI  - ?

PMID- 29579756
TI  - ?

PMID- 29579757
TI  - Liberal versus Indicated Maternal Oxygen Supplementation in Labor: A Before-and
      After Trial.
AB  - BACKGROUND:  Although supplemental oxygen (SO2) is routinely administered to
      laboring gravidas, benefits and harms are not well studied. OBJECTIVE:  This
      article compares strategies of liberal versus indicated SO2 therapy during labor
      on cesarean delivery (CD) rate and neonatal outcomes. STUDY DESIGN:  A
      controlled, before-and-after trial of laboring women with term, singleton
      pregnancies. During an initial 8-week period, maternal SO2 was administered at
      the discretion of the provider followed by an 8-week period where SO2 was to be
      given only for protocol indications. RESULTS:  Our study included 844 women.
      There was no difference in number of women receiving SO2 (53% liberal vs. 50%
      indicated; p = 0.33). For those receiving SO2, there was no difference in SO2
      duration (median, 89 minutes [interquartile range, 42-172] vs. 87 minutes [36
      152]; p = 0.42). There were no differences in overall CD rate (20% vs. 17%; p =
      0.70), CD for nonreassuring fetal status, or use of intrauterine resuscitative
      measures. There were more 5-minute APGAR < 7 in the indicated group, but no
      difference in umbilical artery pH < 7.1 or neonatal intensive care unit (NICU)
      admission. CONCLUSION:  Approximately half of women receive SO2 intrapartum
      regardless of a strategy of liberal or indicated oxygen use. There were no
      clinically significant differences in outcomes between strategies.

PMID- 29579758
TI  - Glucose Gel in Infants at Risk for Transitional Neonatal Hypoglycemia.
AB  - OBJECTIVE:  To evaluate whether glucose gel as a supplement to feedings in
      infants admitted to the newborn nursery at risk for neonatal hypoglycemia (NH)
      reduces the frequency of transfer to a higher level of care for intravenous
      dextrose treatment. STUDY DESIGN:  We revised our newborn nursery protocol for
      management of infants at risk for NH to include use of 40% glucose gel (200
      mg/kg). Study population included late preterm, small and large for gestational
      age infants, and infants of diabetic mothers. We compared outcomes before (4/1/14
      3/31/15: Year 1) and after (4/1/15-3/31/16: Year 2) initiation of the revised
      protocol. Our prospective primary outcome was transfer to the neonatal intensive
      care unit (NICU) for treatment with a continuous infusion of dextrose. RESULTS: 
      NICU transfer for management of NH fell from 8.1% in Year 1 (34 of 421 at-risk
      infants screened) to 3.7% in Year 2 (14 of 383 at-risk infants screened). Rate of
      exclusive breastfeeding increased from 6% in Year 1 to 19% in Year 2. Hospital
      charges for the study population decreased from 801,276 USD to 387,688 USD in
      Year 1 and Year 2, respectively. CONCLUSION:  Our study supports the adjunctive
      use of glucose gel to reduce NICU admissions and total hospitalization expense.

PMID- 29579759
TI  - Risk Factors for Neonatal Hypoxic-Ischemic Encephalopathy in the Absence of
      Sentinel Events.
AB  - OBJECTIVE:  Hypoxic-ischemic encephalopathy (HIE) may be associated with
      intrapartum sentinel events or may be unexplained. We sought to identify risk
      factors for unexplained HIE cases and compare their morbidity and mortality to
      cases associated with sentinel events. STUDY DESIGN:  Retrospective cohort study
      of all neonates admitted with suspected HIE treated with whole-body hypothermia
      from January 2007 through July 2017. Cases of unexplained HIE were compared with
      those with a sentinel event. RESULTS:  A total of 223 neonates met the inclusion
      criteria, of which 86 (38.6%) experienced a sentinel event and 137 (61.4%) did
      not. Placental histopathology was performed for 28/31 (90.3%) and 48/53 (90.6%)
      inborn neonates with and without sentinel events, respectively. Placentas from
      unexplained HIE cases more often exhibited histologic chorioamnionitis (43.8% vs.
      17.9%, p = 0.02) and funisitis (25% vs. 3.6%, p = 0.02). Neonatal morbidity and
      mortality were similar. On multivariable regression, nulliparity (odds ratio
      [OR], 4.11, 95% confidence interval [CI]: 1.24-13.62) and histologic funisitis
      (OR, 20.33, 95% CI: 1.11-373.4) remained significant. CONCLUSION:  Other than
      nulliparity and infection which could be identified on umbilical cord examination
      following delivery but not on clinical assessment prior to delivery, there are no
      other identifiable risk factors for HIE in the absence of a sentinel event, and
      morbidity and mortality are similar between groups.

PMID- 29579760
TI  - Genetics of Lithium Response in Bipolar Disorder.
AB  - INTRODUCTION: Lithium remains the best-established long-term treatment for
      bipolar disorder because of its efficacy in maintaining periods of remission and
      reducing the risk of suicide. Not all patients successfully respond to lithium
      treatment, and the individual response, including the occurrence of side effects,
      is highly variable and not easy to predict. The genetic basis of lithium response
      is supported by the fact that the response clusters in families. Likewise, recent
      high-throughput genomic analyses have shed light on its genetic architecture.
      METHODS: This nonsystematic review summarizes the main results obtained in
      genetic association studies using lithium response as target trait. RESULTS:
      These studies suggest that several genetic loci might modulate the way a patient
      responds to lithium maintenance treatment. Further studies to fully characterize
      the genetic architecture of lithium response are warranted. DISCUSSION: The
      identification of genetic factors associated with lithium response will be
      important for (1) better understanding of lithium's mode of action and (2)
      development of a predictive model for optimization of long-term treatment of
      bipolar disorder.

PMID- 29579761
TI  - Surgical Site Infection in a Tertiary Neonatal Surgery Centre.
AB  - INTRODUCTION:  Surgical site infection (SSI) is a key performance indicator to
      assess the quality of surgical care. Incidence and risk factors for SSI in
      neonatal surgery are lacking in the literature. AIM:  To define the incidence of
      SSI and possible risk factors in a tertiary neonatal surgery centre. MATERIALS
      AND METHODS:  This is a prospective cohort study of all the neonates who
      underwent abdominal and thoracic surgery between March 2012 and October 2016. The
      variables analyzed were gender, gestational age, birth weight, age at surgery,
      preoperative stay in neonatal intensive care unit, type of surgery, length of
      stay, and microorganisms isolated from the wounds. Statistical analysis was done
      with chi-square, Student's t- or Mann-Whitney U-tests. A logistic regression
      model was used to evaluate determinants of risk for SSI; variables were analyzed
      both with univariate and multivariate models. For the length of hospital stay, a
      logistic regression model was performed with independent variables. RESULTS:  A
      total of 244 neonates underwent 319 surgical procedures. The overall incidence of
      SSIs was 43/319 (13.5%). The only statistical differences between neonates with
      and without SSI were preoperative stay (<4 days vs. >=4 days, p < 0.01) and
      length of hospital stay (<30 days vs. >=30 days, p < 0.01). A pre-operative stay
      longer than 4 days was associated with almost three times increased risk of SSI
      (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.05-8.34, p = 0.0407).
      Gastrointestinal procedures were associated with more than ten times the risk of
      SSI compared with other procedures (OR 10.17, 95% CI 3.82-27.10, p < 0.0001).
      Gastroschisis closure and necrotizing enterocolitis (NEC) laparotomies had the
      highest incidence SSI (54% and 62%, respectively). The risk of longer length of
      hospital stay after SSI was more than three times higher (OR = 3.36, 95%CI 1.63
      6.94, p = 0.001). CONCLUSION:  This is the first article benchmarking the
      incidence of SSI in neonatal surgery in the United Kingdom. A preoperative stay
      >=4 days and gastrointestinal procedures were independent risk factors for SSI.
      More research is needed to develop strategies to reduce SSI in selected neonatal
      procedures.

PMID- 29579762
TI  - Strategies in Development and Delivery of Nanotechnology Based Cosmetic Products.
AB  - The science of formulation involving cosmetic ingredients has always been a
      challenge since the release of active components greatly depends upon the carrier
      system involved and the selectivity of skin barrier. The principle obstacle of
      the skin resides in the epidermis and it's hard for many active components to
      cross it. The formulation related factors like size of particles, viscosity and
      lipophilicity of the components also play an important role in permeation of the
      dermal composition. Though widely used; conventional creams and gels still
      struggle in terms of success. This work focuses on nano based formulation
      strategies for successful delivery of cosmetic agents. Novel strategies like
      nanoemulsion, nanogels, liposomes, aquasomes, niosomes, dendrimers and fullerenes
      have paved way for successful delivery of dermal formulations to desire depths in
      the skin.

PMID- 29579763
TI  - Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a
      Randomised Withdrawal Design.
AB  - INTRODUCTION: Previous findings from a pragmatic trial suggest that usual care
      compared with usual care plus individualised homeopathy is not a feasible design
      to address homeopathic interventions for asthma. OBJECTIVE: The main purpose of
      this article was to investigate the feasibility of the randomised withdrawal
      design as a strategy to assess the effectiveness of a standardised clinical
      pharmaceutical homeopathic protocol (Organon.modus) on perennial asthma in
      adolescents. METHODS: Randomised withdrawal, double-blind, parallel, placebo
      controlled, 12-week study. PATIENTS: 12 to 17 years old adolescents, with the
      diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol
      for wheezing episodes), who achieved 3 months of well-controlled asthma, after a
      variable period of individualised homeopathic treatment according to
      Organon.modus protocol. SETTING: a secondary care medical specialist centre.
      INTERVENTION: continuation with the individualised homeopathic medicine or with
      indistinguishable placebo during 12 weeks of beclomethasone step-down. PRIMARY
      OUTCOME: number of days of well-controlled asthma. Secondary measures: number of
      days of fenoterol use, number of visits to an emergency service (without
      hospitalisation) and percentage of patients excluded due to an exacerbation
      characterising a partly controlled asthma. Tolerability was assessed by Adverse
      Events, registered at every visit. RESULTS: Nineteen patients were randomised to
      continue treatment with homeopathy and 21 with placebo. Effectiveness measures
      for the homeopathy and placebo groups respectively were median number of days of
      good clinical control: 84 versus 30 (p = 0.18); median number of days of
      fenoterol use per patient: 3 versus 5 (p = 0.41); visits to an emergency room: 1
      versus 6 (p = 0.35); percentage of exclusion due to partly controlled asthma:
      36.8% versus 71.4% (p = 0.05). Few Adverse Events were reported. CONCLUSIONS:
      This pilot study supports the feasibility of the double-blind randomised
      withdrawal design in studies investigating homeopathy on teenage asthma, when
      performed by specialists following a standardised clinical-pharmaceutical
      homeopathic protocol. CLINICAL TRIAL REGISTRATION: RBR-6XTS8Z.

PMID- 29579764
TI  - Lung Transplantation: Controversies and Evolving Concepts.

PMID- 29579765
TI  - Selection of Candidates for Lung Transplantation and Controversial Issues.
AB  - Lung transplantation is a widely accepted treatment to manage the advanced stages
      of many lung diseases that have failed to respond to all other therapeutic
      interventions. There have been ever-expanding indications for lung
      transplantation as a treatment for lung disease. The International Society for
      Heart and Lung Transplantation (ISHLT) updated guidelines for candidate selection
      in 2014. This document was published to serve as a guide in selecting appropriate
      candidates for lung transplantation. Ideal candidates for lung transplantation
      are those with near-end stage disease, limited life expectancy due to their lung
      disease, and who experience significant loss in quality of life. At the same
      time, candidates should be free of significant comorbidities that might
      negatively impact successful transplantation. Despite well thought out published
      guidelines for candidate selection, many controversial issues surrounding
      selection of lung transplant candidates remain. This review will focus on some of
      the more common controversial issues and explain how most centers approach these
      issues when choosing candidates for lung transplantation.

PMID- 29579766
TI  - How Should Lungs Be Allocated for Transplant?
AB  - As lung transplantation became established therapy for end-stage lung disease,
      there were not nearly enough suitable lungs from brain-dead organ donors to meet
      the need, leading to a focus on how lungs are allocated for transplant.
      Originally lungs were allocated by the United Network for Organ Sharing (UNOS)
      like hearts-by waiting time, first to listed recipients in the organ procurement
      organization of the donor, then to potential recipients in concentric 500
      nautical mile circles. This resulted in long waiting times and increasing
      waitlist deaths. In 1999, the Health Resources and Services Administration
      published a Final Rule, requesting UNOS to review organ allocation algorithms to
      ensure that they complied with the desire to allocate organs based on urgency,
      avoiding futile transplants, and minimizing the role of waiting time in organ
      allocation. This led to development of the lung allocation score (LAS), which
      allocates lungs based on urgency and transplant benefit, introduced in 2005. The
      U.S. LAS system was adopted by Eurotransplant to allocate unused lungs between
      donor countries, and by both Germany and the Netherlands for lung allocation in
      their countries. This article will review the history of lung allocation, discuss
      the impact of LAS and its shortcomings, suggest recommendations to increase the
      number of lungs for transplant, and improve allocation of donated lungs.
      Ultimately, the goal of organ transplant research is to have so many organs to
      transplant that allocation systems are unnecessary.

PMID- 29579767
TI  - Donation after Brain Death versus Donation after Circulatory Death: Lung Donor
      Management Issues.
AB  - Lung transplantation (LTx) has traditionally been limited by a lack of suitable
      donor lungs. With the recognition that lungs are more robust than initially
      thought, the size of the donor pool of available lungs has increased dramatically
      in the past decade. Donation after brain death (DBD) and donation after
      circulatory death (DCD) lungs, both ideal and extended are now routinely
      utilized. DBD lungs can be damaged. There are important differences in the
      public's understanding, legal and consent processes, intensive care unit
      strategies, lung pathophysiology, logistics, and potential-to-actual donor
      conversion rates between DBD and DCD. Notwithstanding, the short- and long-term
      outcomes of LTx from any of these DBD versus DCD donor scenarios are now similar,
      robust, and continue to improve. Large audits suggest there remains a large
      untapped pool of DCD (but not DBD) lungs that may yet further dramatically
      increase lung transplant numbers. Donor scoring systems that might predict the
      donor conversion rates and lung quality, the role of ex vivo lung perfusion as an
      assessment and lung resuscitation tool, as well as the potential of donor lung
      quality biomarkers all have immense promise for the clinical field.

PMID- 29579768
TI  - Chronic Lung Allograft Dysfunction: Evolving Concepts and Therapies.
AB  - Lung transplantation has become an established therapeutic option for a variety
      of end-stage lung diseases. Technical advances in graft procurement,
      implantation, perioperative care, immunosuppression, and posttransplant medical
      management have led to significant improvements in 1-year survival, but outcomes
      after the first year have improved minimally over the last two decades. The main
      limitation to better long-term survival after lung transplantation is chronic
      lung allograft dysfunction (CLAD). CLAD also impairs quality of life and
      increases the costs of medical care. Our understanding of CLAD manifestations,
      risk factors, and mechanisms is rapidly evolving. Recognition of different CLAD
      phenotypes (e.g., bronchiolitis obliterans syndrome and restrictive allograft
      syndrome) and the unique pathogenic mechanisms will be important for developing
      novel therapies. In addition to alloimmune-mediated rejection, we now recognize
      the importance of alloimmune-independent mechanisms of injury to the allograft.
      CLAD is the consequence of dysregulated repair of allograft injury.
      Unfortunately, currently available therapies for CLAD are usually not effective.
      However, the advances in knowledge, reviewed in this manuscript, should lead to
      novel strategies for CLAD prevention and treatment, as well as improvement in
      long-term outcomes after lung transplantation. We provide an overview of the
      evolving terminology related to CLAD, its varying clinical phenotypes and their
      diagnosis, natural history, pathogenesis, and potential treatments.

PMID- 29579769
TI  - Immunosuppression: Have We Learnt Anything?
AB  - Outcomes after lung transplantation remain disappointing because there is a high
      incidence of chronic lung allograft dysfunction (CLAD), which typically follows a
      progressive clinical course and often results in allograft failure and death.
      Chronic rejection is considered the predominant cause of CLAD. Thus, optimal
      immunosuppression has been viewed as having the potential to prevent CLAD and
      improve survival after lung transplantation. Numerous clinical trials have been
      conducted investigating the efficacy and safety of various immunosuppressive
      agents. Many studies have been small and single-center clinical trials but some
      have been international and multicenter trials enrolling more than 300 patients.
      This review focuses on clinical trials of immunosuppression conducted in lung
      transplantation and points out strengths and limitations of the various studies.
      Ultimately, the findings of these clinical trials explain the current state of
      practice in lung transplantation and identify gaps in knowledge that require
      additional study. Finally, there is an ongoing need for carefully designed and
      conducted clinical trials to improve clinical practice and outcomes after lung
      transplantation.

PMID- 29579770
TI  - Acute Cellular Rejection: Is It Still Relevant?
AB  - Despite significant progress in the field of transplant immunology, acute
      cellular rejection (ACR) remains a very frequent complication after lung
      transplantation (LTx), with almost 30% of LTx recipients experiencing at least
      one episode of treated ACR during the first year of follow-up. Most episodes
      respond to the first-line immunosuppressive treatment and are rarely a direct
      cause of death. However, the association of ACR with later adverse outcomes, such
      as chronic lung allograft dysfunction, bronchial stricture, and infectious
      complications associated with the intensification of immunosuppression,
      negatively impacts long-term survival. The burden imposed on patients and health
      care resources is even higher in cases of refractory or recurrent ACR, which
      accelerates lung function decline. Although important laboratory and clinical
      research conducted over the last two decades has improved our understanding of
      the mechanisms underlying ACR, there are still many uncertainties about the risk
      factors for ACR, the optimal monitoring strategies, and the prediction of long
      term outcomes. These knowledge gaps contribute to the large variability in
      clinical practice among LTx centers, which renders multicenter studies of ACR
      challenging. In this review, we summarize current evidence on the epidemiology,
      pathogenesis, and risk factors of ACR. We describe diagnostic and therapeutic
      approaches that are currently used in the clinical practice and also review
      promising diagnostic tools that are under investigation. Associations between ACR
      and other adverse outcomes of LTx are examined. Finally, within each topic of
      discussion, we highlight the main areas of controversy and opportunities for
      future research.

PMID- 29579771
TI  - The Human Respiratory Microbiome: Implications and Impact.
AB  - Once considered a sterile site below the larynx, the tracheobronchial tree and
      parenchyma of the lungs are now known to harbor a rich diversity of microbial
      species including bacteria, viruses, fungi, and archaea. Many of these organisms,
      particularly the viruses which comprise the human respiratory virome, have not
      been identified, so their true role is unknown. It seems logical to conclude that
      a "healthy" respiratory microbiome exists which may be modified in disease states
      and perhaps by therapies such as antibiotics, antifungals, and antiviral
      treatments. It is likely that there is a critical relationship or equilibrium
      between components of the microbiome until such time as perturbations occur which
      lead to a state of dysbiosis or an "unhealthy" microbiome. The act of lung
      transplantation provides an extreme change to an individual's respiratory
      microbiome as, in effect, the donor respiratory microbiome is transplanted into
      the recipient. The mandatory ex-vivo period of the donor lungs appears to be
      associated with blooms of resident viral species in particular. Subsequently,
      allograft injury, rejection, and immune suppressive therapy all combine to create
      periods of dysbiosis which when combined with transient infections such as
      community acquired respiratory viruses may facilitate the development of chronic
      allograft dysfunction in predisposed individuals. As our understanding of the
      respiratory microbiome is rapidly expanding, based on the use of new-generation
      sequencing tools in particular, it is to be hoped that insights gained into the
      subtle relationship between the microbiome and the lung allograft will facilitate
      improved outcomes by directing novel therapeutic endeavors.

PMID- 29579772
TI  - Community-Acquired Respiratory Viruses.
AB  - The incidence of community-acquired respiratory viruses (CARVs) is ~15 cases per
      100 patient-years after lung transplantation (LTx). Paramyxoviruses account for
      almost 50% of the cases of CARV infection in LTx. Most patients will be
      symptomatic with a mean decline of 15 to 20% in forced expiratory volume in 1
      second. The attributable death rate is low in recent years 15 to 25% CARV
      infected LTx patients will develop chronic lung allograft dysfunction within a
      year after CARV infection. This risk seems to be increased in comparison to the
      noninfected LTx recipient.Detection rate of CARV dependent on clinical awareness,
      sampling, and diagnostic method with nucleic acid testing by polymerase chain
      reaction in bronchoalveolar lavage is the gold standard after LTx.There is no
      approved treatment for paramyxoviruses, most centers use ribavirin by various
      routes. Toxicity of systemic ribavirin is of concern and some patients will have
      contraindication to this treatment modality. Treatment may reduce the risk to
      develop chronic lung allograft dysfunction and respiratory failure. Agents under
      development are inhibiting viral attachment and use silencing mechanisms of viral
      replication.

PMID- 29579773
TI  - Surveillance Bronchoscopy: Is It Still Relevant?
AB  - The performance of bronchoscopy with bronchoalveolar lavage and transbronchial
      biopsy is an essential tool and skill required by any clinician caring for
      patients postlung transplantation. Making a confident diagnosis is crucial in
      initiating different treatment strategies which may be in turn hazardous to the
      patient in light of an inaccurate diagnosis. Having more information available
      for evaluation optimizes the chances of tailoring appropriate therapeutic options
      in this complex patient population. Performing a bronchoscopy with
      bronchoalveolar lavage and transbronchial biopsy indeed provides a wealth of
      information via microbiological, cytological, and histological samples that
      assist us to differentiate infection from rejection, or to confirm the presence
      of both. This review aims to discuss the utility of bronchoscopy postlung
      transplantation in the diagnosis of rejection, infection, and airway
      complications, as well as looking into the ongoing controversy regarding
      monitoring practices worldwide and safety concerns.

PMID- 29579774
TI  - Fungal Infections Complicating Lung Transplantation.
AB  - Lung transplantation is an increasingly utilized modality for treating advanced
      lung disease. However, lung transplant recipients (LTRs) experience high rates of
      infection-related mortality and, compared with other solid organ transplant
      recipients, are at increased risk of infectious complications given the intensity
      of immunosuppression employed, the presence of airway abnormalities after surgery
      and exposure of the allograft to the environment. Fungal infections, particularly
      mold infections, are problematic after transplantation as they are often
      associated with limited treatment options and poor outcomes. We describe the non
      Candida fungal infections occurring in LTRs, including their epidemiology,
      clinical features, and treatment.

PMID- 29579775
TI  - Defining Success in Lung Transplantation: From Survival to Quality of Life.
AB  - Lung transplantation (LT) has the potential to extend survival and improve
      quality of life (QOL) for patients suffering from end-stage lung disease. This
      review describes the many ways in which success can be defined in LT. It
      evaluates the improvements in survival outcomes after LT over time, and describes
      ways to measure the success of LT other than survival after transplantation. It
      also addresses the importance of patient-centered outcomes and how improvements
      in health-related quality of life (HRQL) are pivotal to defining success within
      LT.

PMID- 29579776
TI  - Linear and nonlinear variable selection in competing risks data.
AB  - Subdistribution hazard model for competing risks data has been applied
      extensively in clinical researches. Variable selection methods of linear effects
      for competing risks data have been studied in the past decade. There is no
      existing work on selection of potential nonlinear effects for subdistribution
      hazard model. We propose a two-stage procedure to select the linear and nonlinear
      covariate(s) simultaneously and estimate the selected covariate effect(s). We use
      spectral decomposition approach to distinguish the linear and nonlinear parts of
      each covariate and adaptive LASSO to select each of the 2 components. Extensive
      numerical studies are conducted to demonstrate that the proposed procedure can
      achieve good selection accuracy in the first stage and small estimation biases in
      the second stage. The proposed method is applied to analyze a cardiovascular
      disease data set with competing death causes.

PMID- 29579777
TI  - Comparing hierarchical models via the marginalized deviance information
      criterion.
AB  - Hierarchical models are extensively used in pharmacokinetics and longitudinal
      studies. When the estimation is performed from a Bayesian approach, model
      comparison is often based on the deviance information criterion (DIC). In
      hierarchical models with latent variables, there are several versions of this
      statistic: the conditional DIC (cDIC) that incorporates the latent variables in
      the focus of the analysis and the marginalized DIC (mDIC) that integrates them
      out. Regardless of the asymptotic and coherency difficulties of cDIC, this
      alternative is usually used in Markov chain Monte Carlo (MCMC) methods for
      hierarchical models because of practical convenience. The mDIC criterion is more
      appropriate in most cases but requires integration of the likelihood, which is
      computationally demanding and not implemented in Bayesian software. Therefore, we
      consider a method to compute mDIC by generating replicate samples of the latent
      variables that need to be integrated out. This alternative can be easily
      conducted from the MCMC output of Bayesian packages and is widely applicable to
      hierarchical models in general. Additionally, we propose some approximations in
      order to reduce the computational complexity for large-sample situations. The
      method is illustrated with simulated data sets and 2 medical studies, evidencing
      that cDIC may be misleading whilst mDIC appears pertinent.

PMID- 29579778
TI  - The sum of standardized residuals: Goodness-of-fit test for binary response
      models.
AB  - We propose a new goodness-of-fit statistic for evaluating generalized linear
      models with binary responses on the basis of the sum of standardized residuals.
      We derive the asymptotic distribution of the sum of standardized residuals
      statistic and argue that, despite its relative simplicity, it typically
      outperforms many of the more sophisticated currently used goodness-of-fit
      statistics.

PMID- 29579780
TI  - Multivariate joint frailty model for the analysis of nonlinear tumor kinetics and
      dynamic predictions of death.
AB  - The Response Evaluation Criteria in Solid Tumors are used as standard guidelines
      for the clinical evaluation of cancer treatments. The assessment is based on the
      anatomical tumor burden: change in size of target lesions and evolution of
      nontarget lesions (NTL). Despite unquestionable advantages of this standard tool,
      Response Evaluation Criteria in Solid Tumors are subject to some limitations such
      as categorization of continuous tumor size or negligence of its longitudinal
      trajectory. In particular, it is of interest to capture its nonlinear shape and
      model it simultaneously with recurrent progressions of NTL and overall survival.
      We propose a multivariate nonlinear mechanistic joint frailty model for
      longitudinal data, recurrent events, and a terminal event. In the model, the
      tumor size trajectory is described using an ordinary differential equation that
      accounts for the natural growth and treatment-induced decline. We perform a
      simulation study to validate the method and apply the model to a phase III
      clinical trial in colorectal cancer. In the results of the analysis, we determine
      on which component, tumor size, NTL, or death the treatment acts mostly and
      perform dynamic predictions of death. We compare the model with other models that
      consider parametric functions or splines for the tumor size trajectory in terms
      of goodness of fit and predictive accuracy.

PMID- 29579779
TI  - Late sodium current inhibitors to treat exercise-induced obstruction in
      hypertrophic cardiomyopathy: an in vitro study in human myocardium.
AB  - BACKGROUND AND PURPOSE: In 30-40% of hypertrophic cardiomyopathy (HCM) patients,
      symptomatic left ventricular (LV) outflow gradients develop only during exercise
      due to catecholamine-induced LV hypercontractility (inducible obstruction).
      Negative inotropic pharmacological options are limited to beta-blockers or
      disopyramide, with low efficacy and tolerability. We assessed the potential of
      late sodium current (INaL )-inhibitors to treat inducible obstruction in HCM.
      EXPERIMENTAL APPROACH: The electrophysiological and mechanical responses to beta
      adrenoceptor stimulation were studied in human myocardium from HCM and control
      patients. Effects of INaL -inhibitors (ranolazine and GS-967) in HCM samples were
      investigated under conditions simulating rest and exercise. KEY RESULTS: In
      cardiomyocytes and trabeculae from 18 surgical septal samples of patients with
      obstruction, the selective INaL -inhibitor GS-967 (0.5 MUM) hastened twitch
      kinetics, decreased diastolic [Ca2+ ] and shortened action potentials, matching
      the effects of ranolazine (10MUM). Mechanical responses to isoprenaline
      (inotropic and lusitropic) were comparable in HCM and control myocardium.
      However, isoprenaline prolonged action potentials in HCM myocardium, while it
      shortened them in controls. Unlike disopyramide, neither GS-967 nor ranolazine
      reduced force at rest. However, in the presence of isoprenaline, they reduced
      Ca2+ -transient amplitude and twitch tension, while the acceleration of
      relaxation was maintained. INaL -inhibitors were more effective than disopyramide
      in reducing contractility during exercise. Finally, INaL -inhibitors abolished
      arrhythmias induced by isoprenaline. CONCLUSIONS AND IMPLICATIONS: Ranolazine and
      GS-967 reduced septal myocardium tension during simulated exercise in vitro and
      therefore have the potential to ameliorate symptoms caused by inducible
      obstruction in HCM patients, with some advantages over disopyramide and beta
      blockers.

PMID- 29579781
TI  - Proportional hazard model estimation under dependent censoring using copulas and
      penalized likelihood.
AB  - This paper considers Cox proportional hazard models estimation under informative
      right censored data using maximum penalized likelihood, where dependence between
      censoring and event times are modelled by a copula function and a roughness
      penalty function is used to restrain the baseline hazard as a smooth function.
      Since the baseline hazard is nonnegative, we propose a special algorithm where
      each iteration involves updating regression coefficients by the Newton algorithm
      and baseline hazard by the multiplicative iterative algorithm. The asymptotic
      properties for both regression coefficients and baseline hazard estimates are
      developed. The simulation study investigates the performance of our method and
      also compares it with an existing maximum likelihood method. We apply the
      proposed method to a dementia patients dataset.

PMID- 29579782
TI  - Identification of a Golgi apparatus protein complex important for the asexual
      erythrocytic cycle of the malaria parasite Plasmodium falciparum.
AB  - Compared with other eukaryotic cell types, malaria parasites appear to possess a
      more rudimentary Golgi apparatus being composed of dispersed, unstacked cis and
      trans-cisternae. Despite playing a central role in the secretory pathway of the
      parasite, few Plasmodium Golgi resident proteins have been characterised. We had
      previously identified a new Golgi resident protein of unknown function, which we
      had named Golgi Protein 1, and now show that it forms a complex with a previously
      uncharacterised transmembrane protein (Golgi Protein 2, GP2). The Golgi Protein
      complex localises to the cis-Golgi throughout the erythrocytic cycle and
      potentially also during the mosquito stages. Analysis of parasite strains where
      GP1 expression is conditionally repressed and/or the GP2 gene is inactivated
      reveals that though the Golgi protein complex is not essential at any stage of
      the parasite life cycle, it is important for optimal asexual development in the
      blood stages.

PMID- 29579783
TI  - Stormwater Management: When Is Green Not So Green?

PMID- 29579784
TI  - SlugIn 1.0: A Free Tool for Automated Slug Test Analysis.
AB  - The correct characterization of aquifer parameters is essential for water-supply
      and water-quality investigations. Slug tests are widely used for these purposes.
      While free software is available to interpret slug tests, some codes are not user
      friendly, or do not include a wide range of methods to interpret the results, or
      do not include automatic, inverse solutions to the test data. The private sector
      has also generated several good programs to interpret slug test data, but they
      are not free of charge. The computer program SlugIn 1.0 is available online for
      free download, and is demonstrated to aid in the analysis of slug tests to
      estimate hydraulic parameters. The program provides an easy-to-use Graphical User
      Interface. SlugIn 1.0 incorporates automated parameter estimation and facilitates
      the visualization of several interpretations of the same test. It incorporates
      solutions for confined and unconfined aquifers, partially penetrating wells, skin
      effects, shape factor, anisotropy, high hydraulic conductivity formations and the
      Mace test for large-diameter wells. It is available in English and Spanish and
      can be downloaded from the web site of the Geological Survey of Spain. Two field
      examples are presented to illustrate how the software operates.

PMID- 29579785
TI  - Grouping methods for estimating the prevalences of rare traits from complex
      survey data that preserve confidentiality of respondents.
AB  - Originally, 2-stage group testing was developed for efficiently screening
      individuals for a disease. In response to the HIV/AIDS epidemic, 1-stage group
      testing was adopted for estimating prevalences of a single or multiple traits
      from testing groups of size q, so individuals were not tested. This paper extends
      the methodology of 1-stage group testing to surveys with sample weighted complex
      multistage-cluster designs. Sample weighted-generalized estimating equations are
      used to estimate the prevalences of categorical traits while accounting for the
      error rates inherent in the tests. Two difficulties arise when using group
      testing in complex samples: (1) How does one weight the results of the test on
      each group as the sample weights will differ among observations in the same
      group. Furthermore, if the sample weights are related to positivity of the
      diagnostic test, then group-level weighting is needed to reduce bias in the
      prevalence estimation; (2) How does one form groups that will allow accurate
      estimation of the standard errors of prevalence estimates under multistage
      cluster sampling allowing for intracluster correlation of the test results. We
      study 5 different grouping methods to address the weighting and cluster sampling
      aspects of complex designed samples. Finite sample properties of the estimators
      of prevalences, variances, and confidence interval coverage for these grouping
      methods are studied using simulations. National Health and Nutrition Examination
      Survey data are used to illustrate the methods.

PMID- 29579786
TI  - Ecballium Elaterium for Gastrointestinal Cancer

PMID- 29579787
TI  - Significant SNPs Related to Telomere Length and Hepatocellular Carcinoma Risk in
      Chronic Hepatitis B Carriers
AB  - Chronic hepatitis B virus (HBV) infection increases the risk of developing
      cirrhosis and hepatocellular carcinoma(HCC) with suspected interactions between
      virus replication and host immune responses. A number of reports havesuggested
      that telomerase function may be involved in chronic hepatitis B (CHB)
      pathogenesis, but positive or negativeassociations with HCC risk remain for
      discussion. Mean telomere length is an indicator of biological aging and it
      hasbeen reported that reduction in NBV carriers compared to normal individuals.
      In somatic cells, telomeres containsimple, tandemly repeated G-rich sequences
      that frequently are reduced by 50 to 200 base pairs at each cell division.Several
      genome-wide association studies (GWAS) in diverse ethnic populations have
      revealed eleven single nucleotidepolymorphisms (SNPs) linked to telomere length.
      Two of these, rs398652 and rs621559, have prognostic value and couldbe used as
      genetic markers. This review describes current knowledge concerning telomerase
      activity and telomere lengthas well as significant polymorphisms in HBV-related
      HCC patients. In particular, to cast light on genotype-phenotypeinteractions, we
      used SNPnexus to evaluate effects of the two SNPs on risk of disease and complex
      disorders.

PMID- 29579788
TI  - Risk Factors for Gastric Cancer: A Systematic Review
AB  - Objective: Gastric cancer is one of the leading causes of death worldwide, with
      many influences contributing to thedisease. The aim of this study was to identify
      the most important risk factors. Methods: This study was conducted in2017 with a
      structured overview in the Science Directe, Scopus, PubMed, Cochrane, Web of
      Science (ISI) databases.In the first step, articles were extracted based on their
      titles and abstracts; the quality of 43 articles was evaluatedusing the STORBE
      tool. Inclusion criteria were studies carried out on human, English language
      (first step), year ofthe study and the study type (second step). Results:
      Finally, 1,381 articles were found, of which 1,269 were excludedin primary and
      secondary screening. In reviewing the references of the remaining 44 papers, 4
      studies were added.Finally, 43 articles were selected for the quality assessment
      process. A total of 52 risk factors for gastric cancer wereidentified and
      classified into nine important categories: diet, lifestyle, genetic
      predisposition, family history, treatmentand medical conditions, infections,
      demographic characteristics, occupational exposures and ionizing
      radiation'.Conclusion: Several environmental and genetic factors are involved in
      the development of gastric cancer. Regardingthe role of changes in 'diet and
      lifestyle', considering appropriate nutrition and improving the level of
      education andawareness of people is vital for early diagnosis and timely
      treatment of this disease, especially in people with a familyhistory and genetic
      predisposition.

PMID- 29579790
TI  - Preface.

PMID- 29579789
TI  - Risk Factors for Cholangiocarcinoma in Thailand: A SystematicReview and Meta
      Analysis
AB  - Background and objective: Cholangiocarcinoma remains a serious public health
      concern in Thailand. While manyof the risk factors for cholangiocarcinoma in
      western countries are well-recognized, it remains unclear whether theyare the
      same in Thailand. We set out to investigate the risk factors for
      cholangiocarcinoma in Thailand. Methods:Starting March 4, 2016, we reviewed
      studies found using pre-specified keywords on SCOPUS, Pro Quest ScienceDirect,
      PubMed, and online public access catalog of Khon Kaen University. Two review
      authors independently screenedstudies for inclusion criteria, extracted data, and
      assessed the studied Risk of Bias. The Newcastle-Ottawa Scale and theJoanna
      Briggs Institute Critical Appraisal Tools were used to assess the quality of
      included studies. The risk effects offactors were estimated as a pooled adjusted
      odds ratio with a 95% confidence interval. The heterogeneity of results
      wasconsidered using the I-square, Tau-square and Chi-square statistics. Results:
      A strong association was found betweencholangiocarcinoma and age, Opisthorchis
      viverrini infection, eating raw cyprinoid fish, family history of cancer,
      liquorconsumption, and taking praziquantel. There was only a mild association
      found between eating nitrite-containing foods,fresh vegetables, education,
      smoking behavior, and sex. No association was found between cholangiocarcinoma
      andeating fermented fish (Pla-ra), northeastern Thai or Chinese sausage, sticky
      rice, meat, chewing betel nut, or eatingfruit. There were two protective factors
      including fresh vegetables consumption and education attainment. Conclusion:There
      are unique risk factors of cholangiocarcinoma in Thailand, including age,
      Opisthorchis viverrini infection, eatingraw cyprinoid fish, family history of
      cancer, liquor consumption, and taking praziquantel.

PMID- 29579791
TI  - Emigration From Puerto Rico to Florida: Multivariate Analysis of Factors That
      Condition Attitudes of the Puerto Rican Population Toward Organ Donation for
      Transplant.
AB  - BACKGROUND: The Puerto Rican population represents one of the largest immigration
      groups in Florida, and this has an impact on the organ transplant donation
      process. Our aim was to analyze attitudes toward organ donation among Puerto
      Ricans who currently reside in the state of Florida (USA). METHODS: The
      population screened consisted of individuals >15 years old, who were born in
      Puerto Rico, living in Florida, and awaiting organs for transplant. All
      participants completed the "PCID-DTO Rios" questionnaire. Random selection was
      done according to stratification. Support from immigration associations in Spain
      was needed for advice on the locations of potential respondents. Study
      participation was anonymized and self-administered. RESULTS: There were 259
      respondents, 37% (n = 95) were in favor of donation, 36% (n = 93) were against
      donation, and 27% (n = 71) were undecided. The variables associated with these
      attitudes were: age (P = .017); civil status (P = .021); level of education (P <
      .001); previous experience with donation and transplant (P < .001); attitude
      toward organ donation of a relative (P < .001); carrying out pro-social
      activities (P < .001); discussing the issue of transplant with the family (P <
      .001) or couple (P < .001); attitude toward incineration (P < .001), burial (P <
      .001), and autopsy (P < .001); fear of mutilation after donation (P < .001); and
      religious beliefs (P < .001). In the multivariate study, it remained an
      independent variable to have discussed the issue at the family level (odds ratio
      = 11.627; P = .009). CONCLUSION: The Puerto Rican study population residing in
      Florida has an unfavorable attitude toward organ donation.

PMID- 29579792
TI  - Differences in Attitudes Toward Living Kidney Donation Among Dominican Immigrants
      Living in Spain and the United States.
AB  - BACKGROUND: The Dominican population has a double-emigration pathway: one is to
      the USA, by proximity, and the other is to Spain, by sociocultural
      identification. Our aim was to determine attitudes toward living organ donation
      among Dominicans residing in Florida (USA) and Spain. METHODS: All study
      participants were at least 15 years old and living in either Florida (USA) or
      Spain, and stratified by gender and age. A questionnaire on attitudes toward
      living kidney donation ("PCID-LKD Rios") was used. The support of immigrant
      associations in Florida and Spain was required to advise on survey locations.
      Data obtained were anonymized and self-administered. RESULTS: The study
      questionnaire was completed by 123 Dominicans, 68% of whom were in favor of
      living related kidney donation. There were differences (P = .004) according to
      the country of residence. Eighty-one percent of Spain's Dominican residents were
      in favor, compared with 56% of Florida's residents. Factors associated with
      attitude toward donation were level of education (P < .001), previous experience
      with organ donation (P = .006), attitude toward cadaveric organ donation (P <
      .001), belief in the possibility of needing a transplant in the future (P =
      .016), discussing the issue with one's family (P = .007), discussing the issue
      with husband/wife/partner (P = .002), carrying out pro-social activities (P =
      .029), religious beliefs (P = .001), and understanding the risk of living kidney
      donation (P = .046). CONCLUSION: Attitudes toward living kidney donation among
      immigrant Dominicans varies between Spain and the USA, with the former showing a
      more positive view.

PMID- 29579793
TI  - Factors That Affect the Attitudes of the Bolivian Population in Spain With Regard
      to Organ Donation for Transplant.
AB  - BACKGROUND: The Bolivian population is an emerging Latin American immigrant group
      in Spain, several of whom have been transplanted or are awaiting transplant. We
      aimed to assess attitudes toward organ donation among Bolivians currently
      residing in Spain. METHOD: The population screened was born in Bolivia but living
      in Spain, stratified by gender and age. The appraisal tool used was a
      questionnaire that assesses attitudes toward organ donation for transplant ("PCID
      DTO Rios"). Support from immigration associations in Spain was needed for advice
      on locations of potential respondents. Survey participation was anonymized and
      the questionnaire was self-administered. Verbal consent was obtained before
      participation. RESULTS: There were 206 respondents: 49% (n = 101) in favor of
      donating their organs after death; 21% (n = 44) against donation; and 30% (n =
      61) undecided. Their attitudes were found to be associated with level of
      education (P = .008), previous experience with donation and transplant (P =
      .011), concern regarding mutilation after donation (P = .002), knowing the
      attitude of their religion toward transplant (P = .001), the opinion of their
      partner (P < .001), and the possibility of needing a future transplant (P =
      .050). In the multivariate study, the main factor was having a partner in favor
      of organ donation (odds ratio = 16.129; P = .003). CONCLUSION: Attitudes toward
      organ donation among Bolivians residing in Spain are far more negative compared
      with rest of the Spanish population, due to various factors.

PMID- 29579794
TI  - Knowledge of the Brain Death Concept Among the Population of Havana, Cuba.
AB  - BACKGROUND: One of the main reasons against organ donation is the fear of
      apparent death due to ignorance of the brain death concept. Our aim was to assess
      knowledge about and acceptance of the brain death concept among the population of
      Havana, Cuba. METHODS: The population screened, stratified by gender and age,
      included those >15 years old and living in Havana, Cuba. The appraisal tool
      utilized was a questionnaire on attitude toward organ donation ("PCID-DTO Rios").
      A random selection of individuals were surveyed according to the stratification.
      Cuba's census data were used. The participation was anonymized and self
      administered. The verbal consent of participants was provided. RESULTS: There
      were 920 respondents: 31% (n = 282) knew the concept of brain death and accepted
      it; 57% (n = 529) did not; and 12% (n = 109) had a misperception, or did not
      accept brain death as a person's death. Those who knew and accepted the concept
      had a more favorable attitude toward their own organ donation after death (85% vs
      61%; P < .001). The psychosocial factors related to the knowledge of brain death
      concept were: the gender (P = .002), to make up for speaking at a family level
      about the organ transplant (P < .001), the couple's opinion about the organ
      donation (P < .001) and the religion (P < .001). CONCLUSION: The brain death
      concept is not well understood in the population of Havana, Cuba.

PMID- 29579795
TI  - Factors That Condition the Attitude Toward Living Related Kidney Donation Among
      Santiago of Cuba's Population.
AB  - INTRODUCTION: Living kidney donation is currently the most important kidney donor
      source in Latin America, and it is necessary to further increase its rates.
      OBJECTIVE: To analyze the attitude toward living kidney donation among the
      Santiago de Cuba's population and to determine the sociopersonal factors with
      which it is associated. METHOD: The population over 15 years old residing in
      Santiago de Cuba, stratified by sex and age, was screened. The "PCID-LKD Rios"
      attitude questionnaire toward living kidney donation was administered to a random
      selection of the people surveyed according to the stratification and the census
      data. The completion was anonymized and self-administered. Verbal consent was
      obtained. RESULTS: The study was completed by 445 people, of whom the 86% (n =
      389) were in favor of living related kidney donation. This attitude is associated
      with the level of education (P < .001); previous experience with organ donation
      (P = .006); attitude toward cadaveric organ donation (P < .001); carrying out of
      prosocial activities (P = .010); discussion of the issue with the family (P <
      .001) and the significant other (P < .001); concern about mutilation after
      donation (P = .001); religious beliefs (P = .001); and assessment of the risk of
      living kidney donation (P < .001). In the multivariate study, the following
      variables persisted: (1) level of education; (2) attitude of cadaveric donation;
      (3) carrying out of prosocial activities; and (4) risk assessment of living
      donation. CONCLUSIONS: Living related donation is very well accepted among the
      Santiago de Cuba's population.

PMID- 29579796
TI  - Algerian Immigrants to Spain: Study of Attitude to the Donation of Organs for
      Transplantation.
AB  - INTRODUCTION: Many Africans are emigrating to the European Economic Community
      from countries with little knowledge of transplantation. This population has not
      yet been studied. OBJECTIVE: Analyze the attitude toward donation among the
      Algerian population living in Spain. METHODS: We studied the population born in
      Algeria and residing in Spain, over 15 years old, and stratified by age and sex.
      Attitude was surveyed using a questionnaire of organ donation for transplantation
      ("PCID-DTO Rios"). Support from African immigration associations was needed to
      advise on the location of potential respondents. The completion was anonymous and
      self-administered. Verbal consent was obtained to assist in the study. RESULTS:
      Of the 441 respondents, 27% (n = 119) were in favor of donation after death, 43%
      (n = 191) were against, and 30% (n = 131) were undecided. The variables
      associated with the attitude toward the donation were sex (P = .033), having
      offspring (P = .027), having commented on the subject of organ transplantation at
      the family level (P < .001), attitude (P < .001), religion (P < .001), and
      partner's opinion on organ donation and transplantation (P < .001). Only 16% of
      the respondents have known a transplant recipient or donor, with this subgroup
      having the most favorable attitude (68% vs 19%, P < .001). CONCLUSIONS: The
      Algerian population emigrant to Spain has a very unfriendly attitude toward the
      donation of their own organs.

PMID- 29579798
TI  - Approach of Social Groups With Little Sensitization to Organ Donation: Pilot
      Study in the Gypsy Population to Assess the Best Approach to Determine the
      Attitude Toward Organ Donation for Transplantation.
AB  - BACKGROUND: There are social groups with very low donation rates, and action is
      needed to try to reverse this situation. The goal of this study was to determine
      which approach is the best to use with the gypsy population in Spain to determine
      their attitude toward organ donation. METHODS: The study population screened was
      the adult gypsy population resident in Spain. An attitude questionnaire regarding
      organ donation for transplant ("PCID-DTO Rios: Questionnaire of "Proyecto
      Colaborativo Internacional Donante" about Organ Donation and Transplant
      [developed by Dr. Rios]") was used as the assessment instrument. In 3 gypsy
      towns, the patriarch was contacted, who agreed to the questionnaire and to inform
      the others of our presence. Two forms of action were valued: (1) a direct
      approach (n = 100), with personal interview; and (2) an alternative approach (n =
      200), which involved leaving the questionnaire in a meeting point of the town and
      collecting the questionnaires at the end of the meeting. The completion was
      anonymous and self-administered. RESULTS: The completion level of the study was
      anecdotal in both groups. The direct approach presented several problems: (1)
      null participation to complete the questionnaire (only 12 questionnaires were
      collected); (2) the attempt to generate empathy and request re-evaluation
      generated in 78% of the cases a hostile environment; and (3) the male population
      presented a harder and more aggressive attitude. With the alternative approach,
      only 10 of the 200 questionnaires left were retrieved, 9 of them blank or
      painted. CONCLUSIONS: The approach of the gypsy population is complex; because of
      their hostile and unfavorable attitude, a more global approach is needed, with
      the collaboration of people of their own ethnic group.

PMID- 29579797
TI  - Does the Attitude Toward Organ Donation Change as a Function of the Country Where
      People Emigrate? Study Between Uruguayan Emigrants to the United States and
      Spain.
AB  - INTRODUCTION: The Uruguayan population is sensitized toward transplantation.
      However, it has not been studied how this awareness can change when emigrating to
      different countries. OBJECTIVE: To analyze the attitude toward cadaveric organ
      donation and living organ donation between the Uruguayan population residing in
      Florida (United States) and the Uruguayan population residing in Spain. METHOD:
      Adults born in Uruguay and residing in Florida and Spain were screened. The
      questionnaire "PCID-DTO Rios" (donation of cadaveric organs) and "PCID-DVR Rios"
      (living renal donation) were used. Subjects were randomly selected according to
      age and gender stratification. Support from Latin-American immigration
      associations in Spain and Florida was needed. The survey was anonymized and self
      administered. Verbal consent was obtained to collaborate in the study. RESULTS:
      Because the emigrant population to Spain is far larger than the emigrant
      population to the United States, a 2:1 proportional sampling was performed (n =
      132). Sixty-seven percent of residents in Spain were in favor of organ donation
      at the time of death compared with 50% among residents in Florida (P = .082), and
      100% of residents in Spain were in favor of living renal donation compared with
      50% of those living in Florida (P < .001). CONCLUSIONS: The attitude toward
      donation is more favorable among Uruguayan emigrants to Spain than emigrants to
      the United States, especially in related kidney donation.

PMID- 29579799
TI  - Is the Incipient Community of Senegalese Emigrants to Spain in Favor of the
      Donation of Related Renal Live?
AB  - BACKGROUND: Senegalese populations are massively migrating to the southern parts
      of the European Union, especially Spain, France, and Italy. The attitude towards
      living kidney donation in this group is little known. The objective of this study
      was to analyze the attitude toward living kidney donation of subjects from the
      population of Senegalese residents in Spain. METHODS: The study subjects were the
      Senegalese population residing in Spain aged >15 years stratified according to
      age and sex, according to census data and immigrant support associations. The
      evaluation instrument used was an attitude questionnaire toward renal live
      transplant ("PCID-DVR" Rios: The questionnaire of the International Collaborative
      Donor Project about Living Kidney Donation ["Proyecto Colaborativo Internacional
      Donante sobre Donacion de Vivo Renal" in Spanish] developed by Dr. Rios). Support
      of African immigration associations was used to advise on the location of
      potential respondents. Fulfillment of the questionnaire was anonymous and self
      administered. Verbal consent was requested for collaboration in the study.
      Student t tests, the chi2 test, Fisher exact test, and a logistic regression
      analysis were used in the statistical analysis. RESULTS: The study included 293
      respondents. Overall, 62% (n = 181) were in favor of renal live donation
      (relatives and close friends); 38% (n = 112) did not consider the possibility of
      renal live donation or they had doubts. This attitude is not related to social
      variables or general information (P > .05). The variables associated with this
      attitude (P < .05) were related to the family environment (especially with the
      partner) and the risk assessment of donating a living kidney. CONCLUSIONS: Based
      on these results, the Senegalese population that has immigrated to Spain has a
      very unfriendly attitude toward renal live donation.

PMID- 29579800
TI  - Psychometric Characteristics of the Attitude Questionnaire Toward the Donation of
      Organs for Transplant (PCID-DTO-RIOS).
AB  - INTRODUCTION: Most psychosocial attitude studies for donors are not evaluated and
      are not valid. Validated questionnaires are necessary to compare results and
      guarantee that they measure what they are intended to measure. OBJECTIVE: To
      analyze the psychometric characteristics of the attitude questionnaire toward the
      donation of one's own organs after death. We evaluated PCID-DTO RIOS
      (Questionnaire of "Proyecto Colaborativo Internacional Donante" about organ
      donation and transplant; donacion y trasplante de organos in Spanish), developed
      by Dr Rios, for its validation in a Spanish-speaking population. METHOD: A sample
      of 600 Spaniards over 18 stratified by age and gender according to the center
      were included. The PCID-DTO-RIOS was used, which allows determination of the
      factors that condition that attitude. Structured analysis was used in several
      stages, with an initial description of the data, exploratory factorial analysis,
      item analysis, and internal factor consistency. RESULTS: The 20 items of the
      questionnaire are grouped into 4 factors, which explain 63.203% of the total
      variance. By factors, this is distributed as follows: factor 1 (6 items) 26.287%;
      factor 2 (7 items) 24.972%; factor 3 (4 items) 6.834%; and factor 4 (3 items)
      5.110%. The analysis of the items and the internal consistency measured through
      Cronbach alpha (alpha1 = .95, alpha2 = .80, alpha3 = .74, and alpha4 = .64)
      support the four-factor composition, with alpha = 0.834. CONCLUSIONS: The
      questionnaire PCID-DTO-RIOS is composed of 4 factors that explain a high
      percentage of the attitude toward the donation of one's own organs after death.

PMID- 29579801
TI  - Guinean Population Emigrant to Spain Has Very Little Awareness of the Donation
      and Transplantation of Organs.
AB  - INTRODUCTION: The Guinean population is an emerging group in Europe, but the
      group's awareness of organ donation and transplantation has not been studied.
      OBJECTIVE: To analyze the attitude toward organ donation among the population
      born in Guinea living in Spain. METHODS: The population older than 15 years, born
      in Guinea, and resident in Spain was studied, stratified by age and sex,
      according to census data and immigrant assistance associations. The valuation
      tool used was the attitude questionnaire toward organ donation PCID-DTO RIOS
      (questionnaire on "Donor International Collaborative Project" on organ donation
      and transplantation developed by Dr Rios). A random selection of people to survey
      was based on stratification. Support from African immigration support
      associations was needed to advise on the location of potential respondents. The
      completion was anonymous and self-administered. A descriptive statistic was
      performed, and Student t, chi2, and Fisher tests and a logistic regression
      analysis were applied. RESULTS: In all, 181 Guineans were surveyed, of whom 32%
      (n = 58) were in favor of the donation of their own organs after death, 32% (n =
      57) were against, and 36% (n = 66) were undecided. The variables that are
      associated with attitude toward donation are separated mainly into 4 large groups
      (P < .001): (1) knowledge about the process of donation and organ
      transplantation; (2) attitude toward the manipulation of the body; (3) religious
      variables; and (4) sociofamily variables, especially in relation to the couple.
      CONCLUSIONS: The Guinean population emigrant to Spain has an unfriendly attitude
      toward organ donation.

PMID- 29579802
TI  - Nigerian Immigrant Population in Spain Is Little Sensitized to Living-Related
      Kidney Donation.
AB  - BACKGROUND: The Nigerian population is an emerging group in Spain and in Europe,
      but their sensitization toward living kidney donation has not been studied. The
      aim of this work was to analyze the attitude toward related renal donation while
      alive among the population born in Nigeria resident in Spain. METHODS: A
      population older than 15 years born in Nigeria and resident in Spain, stratified
      by age and sex, was studied with the use of the attitude questionnaire about
      living kidney donation, "PCID-DVR-Rios." People were randomly selected based on
      stratification. African immigration support associations advised on the location
      of potential respondents. Completion of the questionnaire was anonymous and self
      administered. Verbal consent was requested to assist in the study. Statistical
      methods included Student t test, chi2, Fisher exact test, and logistic regression
      analysis. RESULTS: A total of 179 respondents were included in the study: 70% (n
      = 125) were in favor of living-related kidney donation, and 30% (n = 54) remained
      against or undecided. This attitude was associated with different psychosocial
      factors: marital status (P = .001), having offspring (P = .029), risk assessment
      of live donation (P < .001), partner's opinion about donation (P < .001),
      previous relationship with donation and/or transplantation (P < .001), religion
      (P < .001), and fear of mutilation after donation (P < .001). In the multivariate
      analysis, the previous relationship with donation and/or transplantation (odds
      ratio, 8.064) persisted as the main related factor. CONCLUSIONS: The Nigerian
      immigrant population in Spain has a less favorable attitude toward living kidney
      donation than the native western European and Spanish population.

PMID- 29579803
TI  - Attitude Toward Organ Donation Related to Personal Preferences for the Final
      Disposition of the Dead Body in Nursing Students in Southeast Spain.
AB  - INTRODUCTION: In organ donation and transplantation (ODT) and in nursing
      students, it is important to know the preferences about the final destination of
      the body once deceased. Whether these future professionals are afraid of this
      issue could influence their attitude toward ODT and future donation rates.
      OBJECTIVE: To analyze the attitude of nursing students toward cremation, burial,
      and autopsy and to determine the factors affecting this attitude. METHODS: A
      sociologic, interdisciplinary, multicenter, and observational study included
      nursing diploma students (n = 750) from 2010 to 2011 at 3 universities in the
      southeast of Spain. A validated questionnaire (PCID-DTO RIOS) was self
      administered and completed anonymously. RESULTS: Questionnaire completion rate
      was 92% (n = 687), with 71% (n = 486) of students accepting cremation as a body
      treatment after death. Those who were not worried about the possible mutilation
      of the body after donation (P < .05) and those who were in favor of deceased
      donation (P < .001) had a greater degree of acceptance. Of the students, 43% (n =
      278) would accept burial of their body, which was related with being in the
      second year (P < .05) of study. Finally, 86% (n = 586) of students would accept
      an autopsy being carried out, if necessary, and this was related with the
      attitude toward ODT (P = .004). CONCLUSIONS: A high percentage of nursing
      students would accept an autopsy being carried out. This degree of acceptance was
      related with a favorable attitude toward organ donation. The appropriate training
      of future nurses in ODT process will optimize their promotion.

PMID- 29579804
TI  - Attitude Toward Organ Donation and Transplantation in Veterinary Students: A
      Multicenter and Stratified Study in Spain.
AB  - BACKGROUND: Veterinarians often hold decision-making positions in the public
      health care system and can therefore influence public opinion about organ
      donation and transplantation (ODT). The aim of this work was to analyze the
      attitude of Spanish veterinary students toward ODT, because they may influence
      public opinion in the future, and to determine the factors that condition it.
      METHODS: This was a sociologic, interdisciplinary, multicenter, observational
      study in Spain. The study population was students studying for a veterinary
      degree in Spain (n = 9000), and a sample of 2815 students (confidence of 99% and
      precision of +/-1%) was stratified by geographic area and academic year. A
      validated questionnaire of attitude toward ODT (PCID-DTO-Rios) was self
      administered and anonymous. RESULTS: Of the 2815 selected students (2790 plus the
      0.9% per type of sample), 2650 completed the questionnaire (response rate,
      94.14%): 83% (n = 2207) of the respondents were in favor of donation and 17%
      against. The following main variables were related to a favorable attitude: being
      female (odds ratio [OR], 0.752; P = .034); knowing a donor (OR, 1.834; P = .003);
      having discussed the matter with one's family (OR, 1.587; P = .002); having
      spoken about the subject in social circles with friends (OR, 1.633; P < .001),
      and being in favor of donating a deceased family member's organs (OR, 2.403; P <
      .001). CONCLUSIONS: Seventeen percent of Spanish veterinary students were not in
      favor of ODT. It is important to know the factors that determine their attitude,
      because this will make it possible to optimize the resources invested in
      campaigns to promote ODT and to take more specific action.

PMID- 29579805
TI  - Multivariate Analysis of Factors That Influence the Attitude of the Ecuadorian
      Population Resident in Spain Toward Living-Related Kidney Donation.
AB  - BACKGROUND: The Ecuadorian population is the largest Latin-American immigrant
      group in Spain. Currently, several Ecuadorians have received transplants or are
      awaiting transplants in Spain. The aim of this work was to analyze the attitude
      toward living kidney donation among the Ecuadorian population residing in Spain.
      METHODS: The population screened were born in Ecuador, residing in Spain, and >15
      years old, stratified by gender and age, and appraised with the use of the
      questionnaire on attitude toward organ donation for transplantation "PCID-DVR
      Rios." Support from immigration associations in Spain was used to advise on the
      location of potential respondents. The completion was anonymous and self
      administered. Verbal consent was obtained. Statistics included Student t test,
      chi2, Fisher exact test, and logistic regression analysis. RESULTS: A total of
      461 respondents were included: 80% (n = 367) were in favor of living-related
      kidney donation (for a relative or close friend). This attitude was associated
      with psychosocial variables that persisted in the multivariate study: 1) female
      gender (odds ratio [OR], 3.086; P = .001); 2) considering oneself a potential
      kidney receptor in the future (OR, 16.949; P = .002); 3) economic incentive in
      the donation (OR, 100; P = .004); and 4) knowing the attitude of their religion
      toward transplantation (OR, 32.258; P < .001). CONCLUSIONS: Living-related
      donation is accepted among the Ecuadorian population residing in Spain and is
      associated with sociopersonal and religious factors.

PMID- 29579806
TI  - Living Kidney Donation Questionnaire (PCID-DVR-Rios): Validation and Psychometric
      Characteristics in a Spanish-Speaking Population.
AB  - BACKGROUND: The attitude toward living kidney donation is important for certain
      promotion campaigns, however, there are few validated questionnaires in this
      regard. The aim of this work was to analyze the psychometric characteristics of
      the attitudes questionnaire about living renal donation, PCID-DVR-Rios
      (Cuestionario del Proyecto Colaborativo Internacional Donante sobre Donacion de
      Vivo Renal [Questionnaire of the International Collaborative Donor Project on
      Living Kidney Donation] developed by Dr Rios) for the validation of the
      questionnaire in population of Spanish speakers. METHODS: The sample studied
      represented the population >18 years of age, native and resident of Spain,
      stratified by age and sex. The measurement instrument was the PCID-DVR-Rios
      questionnaire. Analysis of data was structured in several stages: an initial
      description of the data, exploratory factor analysis, item analysis, and internal
      consistency of the factors. RESULTS: The questionnaire consists of 11 items,
      distributed in 3 factors of 6, 3, and 2 items. This structure accounts for
      63.995% of the total variance. By factors, the variance is distributed as
      follows: factor 1: 38.461%; factor 2: 14.228%; and factor 3: 11.306%. The
      analysis of items and internal consistency supported the trifactorial
      composition. Each factor is internally consistent (alpha1 = .80; alpha2 = .70;
      alpha3 = .55). CONCLUSIONS: The analyzed dimensions of the PCID-DVR Rios
      questionnaire to analyze attitude toward living kidney donation showed a good fit
      in terms of factorial validity and internal consistency values.

PMID- 29579807
TI  - Council of Europe Black Sea Area Project: International Cooperation for the
      Development of Activities Related to Donation and Transplantation of Organs in
      the Region.
AB  - BACKGROUND: In 2011, the European Directorate for the Quality of Medicines &
      Healthcare of the Council of Europe launched a 3-year collaborative project to
      address the organ shortage and improve access to transplant health services in
      Council of Europe member states in the Black Sea area (Armenia, Azerbaijan,
      Bulgaria, Georgia, Moldova, Romania, Turkey, Ukraine, and the Russian Federation)
      through the development of safe and ethical donation and transplantation
      programs. OBJECTIVE: Support the development of donation and transplantation
      programs through close interstate cooperation between national health
      organizations and relevant stakeholders. METHODOLOGY: Several work packages (WP)
      were established: WP1, project coordination (European Directorate for the Quality
      of Medicines & Healthcare); WP2, development and implementation of an effective
      legislative and financial framework (Czech Republic and France); WP3,
      establishment of National Transplant Authorities (Italy and Portugal); and WP4,
      clinical practices (DTI Foundation). Data collection, surveys, and expert visits
      allowed for the collection of first-hand information from each participant
      country at national, regional, and hospital levels. RESULTS: Data analysis showed
      the positive impact of the project represented by a tendency to increase the
      total donation rates (per million people) in the participant countries (2011 vs
      2013): Azerbaijan, +7.3; Armenia, -0.7; Georgia, +3.3; Bulgaria, +0.9; Moldova,
      +2.5; Ukraine:, +0.8; Romania, +2.3; and Turkey, +2.7. CONCLUSIONS: Increases in
      total donation rates are the result of a number of initiatives in the Black Sea
      area, including the stepwise implementation of legislative, organizational and
      institutional country-specific recommendations tailored by the CoE, efforts of
      the respective Ministries of Health in each country and synergism with other
      European projects in the region. These countries should invest further in
      implementing the recommendations that emerged from this project to improve their
      organ donation and transplantation programs and progress toward self-sufficiency.

PMID- 29579808
TI  - The Process of Kidney Donation in the Northern Macroregional Area of Parana,
      Brazil.
AB  - INTRODUCTION: The high morbidity and mortality caused by chronic kidney disease,
      and consequently, the increase in the need for kidney transplants, makes the
      evaluation of the kidney donation process relevant to verifying the service's
      fragility with the goal of optimizing this process. OBJECTIVE: This study
      analyzed the process of kidney donation in the Northern Macroregional area of
      Parana, Brazil. METHOD: This was a cross-sectional and retrospective evaluation
      study based on 586 reports of deaths provided by the Intra-Hospital Organ
      Donation and Transplant Tissue Commissions to the Organ Procurement Organization
      of the Northern Macroregional area of Parana in Brazil between 2011 and 2015.
      Data were analyzed by descriptive statistics, prevalence ratio, and Poisson
      regression. RESULTS: The prevalence of kidney donation was higher among the
      deaths of individuals younger than 61 years of age (P = .018) due to traumatic
      brain injury and hemorrhagic cardiovascular accident (P < .001), assisted in
      private institutions (P = .037), and occurring in the second half of the year (P
      = .015). CONCLUSION: The process of kidney donation was mainly compromised due to
      the refusal of the family and was associated with clinical and organizational
      aspects.

PMID- 29579809
TI  - Access to Grafts in a Liver Transplant Center: Does It Rely on the Severity of
      the Waiting List Population?
AB  - BACKGROUND: The number of transplants performed relies, partially, on recipients'
      variables on the waiting list. The goal of this study was to compare recipients
      from a high-volume liver center in Argentina with the rest of the country.
      METHODS: This study was a retrospective analysis of liver transplant recipients
      nationally between January 2013 and April 2017. It involved extracting data from
      the open database CRESI-SINTRA (the Argentinian database of the National
      Procurement Organization, an equivalent to the United Network for Organ Sharing);
      expressing results by percentages, medians, and interquartile ranges (IQRs); and
      comparing the national population with the population transplanted at Hospital El
      Cruce (HEC). The Mann-Whitney U test was used for analysis. RESULTS: Nationally,
      1434 liver transplants were performed. A total of 177 (12.34%) were emergency
      status; 811 (56.6%) were by the Model for End-Stage Liver Disease (MELD) (n =
      759)/PELD (Pediatric End-Stage Liver Disease) (n = 52), with a median graft
      assignment position of 5 (IQR, 3-10) in 57.2 days (IQR, 11-217). Median MELD
      access was 29 points (IQR, 24-33). A total of 446 (31.1%) had MELD exceptions;
      249 (55.8%) of these were due to Milan hepatocellular carcinoma. At the HEC, 167
      liver transplantations were performed; 26 (15.6%) were emergency status and 97
      (58.1%) by MELD (none PELD). Their median graft assignment position was 4 (IQR, 4
      16) in 19.1 days (IQR, 4-90); median MELD access was 28 points (IQR, 24-31).
      Forty-five patients (26.9%) had MELD exceptions; 31 (68.9%) were due to
      hepatocellular carcinoma. CONCLUSIONS: Our center has a larger proportion of
      recipients transplanted by emergency status and MELD, similar MELD access, and
      less waiting list time, reflecting our wide policy of liver graft acceptance.

PMID- 29579810
TI  - Trend Analysis of Organ and Tissue Donation for Transplantation.
AB  - BACKGROUND: The goal of this study was to identify the tendency toward donations
      of tissue and organs from donors with brain death between 2001 and 2016 as
      registered by an organ procurement organization in Sao Paulo City. METHODS: This
      quantitative, retrospective, exploratory study encompassed all Tissue and Organ
      Donation Terms signed between 2001 and 2016. A logistic regression model was
      applied to verify whether there was an upward or downward trend in donation.
      RESULTS: After statistical analysis, a significant change trend was identified in
      skin, bones, valve, vessel, heart, lung, and pancreas donations, indicating an
      increase in the donation rate through the years. The donation rate did not show
      changes over the years for donations of liver, kidneys, and corneas. CONCLUSIONS:
      The decision-making process regarding organ and tissue donation is restricted not
      only to the dilemma of whether to donate but another question then arises as
      well: which organs and tissues are to be donated? The discrepancy between the
      authorization for organ donation and the authorization for tissue donation, as
      well as the option for one or another organ and/or tissue, must be thoroughly
      examined because these factors directly affect the number of transplants and
      acquirements effectively accomplished. These factors may be related to explaining
      to one's relatives aspects of the surgery, body reassembling, and usage of such
      organs and/or tissues. They may also be related to the lack of knowledge
      concerning organ donation and the symbolism represented by the organ and/or
      tissue, among other factors.

PMID- 29579811
TI  - Bone Tissue Donation: Tendency and Hurdles.
AB  - INTRODUCTION: The aim of this study was to identify the percentage of bone tissue
      donation in a brain death situation and the tendency of donation rate of this
      tissue in an organ procurement organization in the county of Sao Paulo from 2001
      to 2016. It is a retrospective and quantitative study, based on the Organ and
      Tissue Donation Term of donors who died of brain death between 2001 and 2016.
      METHODS: A logistic regression model was applied, and the odds of donation were
      identified throughout the years, regarding the odds ratio different from zero.
      Finally, it was measured the accuracy of the odds ratio through the confidence
      interval. RESULTS: The analysis has shown a significant change on the trend of
      bone donation (P < .001). In this case, the odds ratio was >1, indicating that
      the donation rate has increased. However, the percentage of growth is still
      considered low. CONCLUSIONS: The study evidences a growth trend regarding the
      donation of bone tissue, but the percentage is still too low to adequately meet
      the demand of patients who need this modality of therapeutic intervention. It is
      believed that educational campaigns of donation are not emphasizing the donation
      of tissues for transplantation, which may be directly impacting their consent
      rates.

PMID- 29579812
TI  - Neurocritical Patient Characteristics Related to Brain Death.
AB  - BACKGROUND: The lack of viable organs for transplantation led to the creation in
      Argentina of the Glasgow 7 Program based on the detection and follow-up of acute
      neurologic patients admitted with Glasgow scores <=7 in selected hospitals. The
      objective of this study was to determine the likelihood of hospitalized acute
      neurologic patients progressing to brain death (BD) based on several variables,
      including age, sex, and admission diagnosis. METHODS: This study was a
      retrospective cohort analysis of data obtained from the SINTRA (Procurement and
      Transplantation National Information System) database between 2006 and 2015.
      Independent variables included the following: age, sex, and diagnosis at
      admission; ischemic stroke; spontaneous intracerebral hematoma (SIH);
      subarachnoid hemorrhage (SH); anoxia, meningitis; penetrating head injury (PHI);
      closed head injury; and tumors. A multivariate analysis was performed adjusting
      the diagnosis at admission according to age and sex. RESULTS: A total of 31,877
      patients were included: 19,308 (61%) patients died and 9736 (30%) evolved to BD.
      Overall, 36% of women and 28% of men evolved to BD (relative risk, 0.87 [95%
      confidence interval (CI), 0.86-0.89]; P < .001). In the multivariate analysis
      adjusted for age and sex, we observed the following: SIH OR, 1.79 (95% CI, 1.69
      1.9; P < .001); ischemic stroke OR, 0.82 (95% CI, 0.73-0.92; P < .001); SH OR,
      2.33 (95% CI, 2.16-2.52; P < .001); anoxia OR, 0.71 (95% CI, 0.64-0.79; P <
      .001); closed head injury OR, 0.41 (95% CI, 0.38-0.43; P < .001); PHI OR, 2.64
      (95% CI, 2.38-2.94; P < .001); and tumors OR, 1.07 (95% CI, 0.93-1.24; P = .31).
      CONCLUSIONS: Thirty percent of the patients who entered the Glasgow 7 Program
      evolved with BD. The characteristics most likely to result in BD were age, female
      sex, PHI, SH, and SIH.

PMID- 29579813
TI  - Does Traumatic Brain Injury by Firearm Injury Accelerates the Brain Death
      Cascade? Preliminary Results.
AB  - Brain death (BD) triggers a series of pathophysiological events similar to
      multiple-organ dysfunction. Traumatic brain injury (TBI) due to firearm injury
      (FAI) causes lesions that could lead to BD. Patients admitted to the ICU due to
      severe TBI that evolved to BD were studied, including those caused by FAI; the 2
      groups were compared with the objective of demonstrating that the support of the
      deceased donor by TBI due to FAI is more unstable and of shorter duration than
      the one related to TBI by another cause. Preliminary results demonstrated that
      the individuals with TBI by FAI died in BD in a higher percentage than the
      individuals with TBI caused by accidents (83% vs 41%). The donor treatment period
      was lower in individuals who presented TBI by FAI. These individuals needed
      higher doses of noradrenaline as vasopressor support for their treatment, without
      showing a statistically significant difference (P = .15), compared with
      individuals whose BD cause was TBI caused by accident.

PMID- 29579814
TI  - Epidemiologic and Evolutionary Profile of Patients With Subarachnoid Hemorrhage
      With Glasgow Coma Scale Score of 8 or Less Who Entered the Follow-Up Program of
      the National Institute of Donation and Transplantation.
AB  - INTRODUCTION: The improvement in understanding the process that determines the
      death of an individual and his or her evolution toward brain death allows
      organization and planning of health policies, optimization of clinical activity
      and management of organ and tissue procurement processes for transplantation.
      OBJECTIVE: This study sought to analyze the epidemiological and evolutionary
      profile of patients with spontaneous subarachnoid hemorrhage (SAH) with a Glasgow
      Coma Scale score (GCS) <=8 who entered follow-up in the Neurocritical Patient
      Monitoring Program (SPN) of Instituto Nacional de Donacion y Trasplante (INDT),
      Uruguay. MATERIALS AND METHODS: SPN, a monitoring and follow-up program for
      neurocritical patients with GCS <= 8, prospectively collected data from 5 public
      and private intensive care units. A total of 160 patients with SAH with GCS <=8
      in 10 years were identified and analyzed using a 2-step nested model. Firstly,
      independent risk factors for mortality were identified, tested in different
      combinations, and one of them was selected using the best correct classification
      rate. In the second step, risk factors for evolution to brain death were
      investigated. RESULTS: The mortality of patients with SAH with GCS <=8 was 68%.
      Mortality for GCS 3 was 82%, significantly higher than for other values on the
      scale (P = .0025). Female sex (P = .011) and arterial hypertension (P = .017)
      were associated with higher mortality. There was no significant association
      between mortality and age, Acute Physiology and Chronic Health Evaluation score,
      and Simplified Acute Physiologic Score II. Administration of analgesia and/or
      sedation was a protective factor (P < .0001). Of the patients who died, 50% were
      in brain death. We did not find clinical elements capable of identifying an
      increased probability of developing brain death. CONCLUSIONS: Based on
      epidemiological data, models capable of improving the understanding of the
      complex process of death and particularly brain death can be generated. More
      studies are needed to explore the differential evolutionary behavior of critical
      neurological illness.

PMID- 29579815
TI  - Utility of Transcranial Doppler in the Coordination of Transplants: 10 Years of
      Experience.
AB  - Transcranial Doppler (TCD) integrated to multimodal neuromonitoring of
      neurocritical patients is a useful tool in the clinical follow-up. A
      retrospective and descriptive study of 194 patients who were admitted into the
      intensive care unit (ICU) was carried out from December 2007 to February 2017. We
      analyzed the distribution of study frequencies with respect to the pathologies
      that motivated them, the characteristics of patients who evolved to brain death
      (BD), and most frequent patterns of cerebral circulatory arrest. Ninety-four of
      the patients that evolved to BD required 126 studies during their follow-up. The
      insonation of the 2 middle cerebral arteries and the basilar artery was the most
      frequent combination (30%). Most frequent reasons of request for a TCD included
      apnea test intolerance and reduction of waiting time and sedation analgesia.
      These 10 years of experience have enabled a deeper understanding of the cerebral
      hemodynamics and the identification of common patterns of high resistance to
      different pathologies (subarachnoid hemorrhage, severe skull trauma, anoxic
      ischemia, ammonia encephalopathy) that explain the severity of the acute brain
      injury, related to the increase of brain volume and its deleterious consequence:
      the elevation of intracranial pressure (ICP). In the same way, because invasive
      ICP monitoring is not available in all cases, with a tomographic scan of the
      skull we have been able to observe a correlation of some imaging signs suggestive
      of intracranial hypertension with patterns of high resistance obtained by the TCD
      in the pathologies mentioned. We recommend that each ICU that assists
      neurocritical patients should have TCD equipment and the skilled personnel to
      carry out the technique.

PMID- 29579816
TI  - Systodiastolic Separation Expresses Cerebral Circulatory Arrest?
AB  - There is a situation before the cerebral circulatory cessation phase, the
      systodiastolic separation in transcranial Doppler (TCD), which may raise doubts
      to the operator technician who performs it. A total of 266 studies were performed
      in 188 neurocritical patients over a 9-year period: 88 cases (77%) corresponded
      to cerebral circulatory arrest (CCA) which accompanies brain death (BD); 9 (5%)
      presented the systodiastolic separation pattern. In 1 of those 9 there was
      persistence of cough reflex and spontaneous breathing; in 5, CCA was not reached;
      only 3 evolved to CCA. The finding of a minimal persistent neurologic semiology
      is a categoric fact that would rule out the clinical correlation between this
      pattern and BD diagnosis.

PMID- 29579817
TI  - Sterility and Safety Validation for Transport Packaging of Organs and Tissues.
AB  - The bags used in the transport of organs and tissues must be sterile, nontoxic,
      pyrogen free, and must serve as a barrier throughout their useful life. The goal
      of this study was to show the sterility, safety, and functionality of the bags
      subjected to irradiation, through validated procedures and techniques. The
      selected sterilization method was the use of gamma radiation. The sterilization
      dose was determined based on validated standards for the sterilization of medical
      products, ISO 11137-2: 2013 and ISO/TS 13004: 2013, using the Verification Dose
      Maximum method on samples belonging to 3 manufacturing lots. The ISO 10993-5:
      2009 standard was used in the cytotoxicity tests, by means of extracts test and
      quantitative technique of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide. The tests to determine the expiration date of the
      kit were performed by ASTM F1980, accelerated aging, and ASTM D3078 to evaluate
      hermeticity. The irradiation dose validated to reach the required sterility
      safety level was 22.5 kGy. The constituent materials and the sterilization method
      do not generated cellular toxicity, and the product was not modified during the
      simulated time of 5 years. Sterilization by irradiation is a method that leaves
      no residue, does not harm the properties of the material because it is conducted
      in cold, and as the sterilizing agent, the energy absorbed by the product is
      highly penetrating and can be treated in its final packaging, with no risk of
      postcontamination. It is for this reason that it is prioritized over other
      methods of sterilization.

PMID- 29579818
TI  - Single-Center Long-Term Follow-Up of Kidney Donors in Argentina (Hospital
      Italiano de Buenos Aires).
AB  - INTRODUCTION: Living kidney donor (LKD) transplantation is increasing due to
      organ shortage. Clinical studies have shown that the risk of developing end-stage
      renal disease (ESRD) in donors is similar to that in the general population. Our
      goal was to evaluate postdonation renal outcomes assessed by glomerular
      filtration rate (GFR), proteinuria, and blood pressure. METHODS: A total of 210
      LKD transplants were performed at Hospital Italiano de Buenos Aires between 2000
      and 2014. Postdonation outcomes were analyzed in 109 donors. GFR was assessed by
      24-hour creatinine clearance (as 24-hour ClCr) and estimated using the
      Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease
      Epidemiology Collaboration (CKD-EPI) equations. Additionally, we correlated the
      predonation renal functional reserve (RFR) with postdonation GFR. Donor results
      were compared to the expected GFR (adjusted to age and single kidney). Other
      renal outcome indicators measured were albuminuria and blood pressure, and they
      were compared (predonation and postdonation) using univariate analysis. RESULTS:
      A total of 109 patients were followed up for 47 +/- 34 months (range, 12-168):
      70% were female, age at donation was 48.58 years (range, 25-70), and predonation
      serum creatinine was 0.85 +/- 0.17 mg/dL. Postnephrectomy GFR (24-hour ClCr) was
      significantly lower compared to predonation GFR (105.38 +/- 21.78 mL/min/1.73 m2
      vs 90.14 +/- 17.78 mL/min/1.73 m2). However, postdonation GFR was not
      significantly different compared to the expected GFR. No differences were found
      for blood pressure or albuminuria. Age >50 and an RFR (<20%) was associated with
      a lower GFR. CONCLUSIONS: In this population of LKD, renal outcome (24-hour CrCl,
      albuminuria, and blood pressure) was within the expected outcome for healthy
      individuals after uninephrectomy.

PMID- 29579819
TI  - Correlation of the Glomerular Filtration Rate Measured With the Use of DTPA-Tc99m
      in Live Kidney Donors With Equations Based on Creatinine and Cystatin C.
AB  - BACKGROUND: Renal donation leads to a risk of developing chronic kidney disease,
      with an incidence of 0.47%. To evaluate for its presence, formulas based on serum
      creatinine are used, but up to 80% of these formulas underestimate the glomerular
      filtration rate (GFR) in donors. The aim of this work was to confirm the highest
      correlation of the GFR as measured with the use of DTPA-Tc99m with the GFR as
      estimated by means of the formula based on serum cystatin C (CKD-EPI creatinine
      cystatin C) in healthy kidney donors. METHODS: In this observational, analytic,
      cross-sectional study, the GFR of kidney donors was determined >=1 year after
      donation by means of DTPA gammagram and estimation with the use of conventional
      formulations and with cystatin C. RESULTS: Of 112 donors, 38 (34%) were included,
      20 (60%) were female, with an overall average age of 40 years, 36.5 months after
      donation, and body mass index of 25.5 kg/m2. Correlation with the GFR as measured
      by means of DTPA gammagram was better with the use of CKD-EPI cystatin C (0.402;
      P = .020) and CKD-EPI creatinine-cystatin (0.549; P < .001) than the conventional
      formulas. Linear correlation with serum cystatin C was 0.825 (P < .001; 95%
      confidence interval, -105.3 to -63.2) for the CKD-EPI cystatin C formula, 0.77 (P
      < .001; -89.9 to -48.1) for the CKD-EPI creatinine-cystatin formula, and 0.525 (P
      = .002; -91.1 to -23.2) for DTPA-Tc99m scintigraphy. CONCLUSIONS: There is a
      strong correlation between estimate the GFR by equations based on cystatin C and
      the measurement of the GFR by DTPA-Tc99m gammagram.

PMID- 29579820
TI  - Correlation of the Renal Cortex Volume With the Glomerular Filtration Rate in
      Live Donors for Renal Transplantation.
AB  - INTRODUCTION: As a pretransplantation evaluation, renal function is determined by
      the glomerular filtration rate (GFR) with the use of renal scintigraphy (RS) and
      the estimated glomerular filtration rate (eGFR). To date, there are few studies
      that correlate renal cortex volume with eGFR determined with renal gammagram (GR)
      and eGFR by equations (Cockroft-Gault, Modification of Diet in Renal Disease, and
      Chronic Kidney Disease Epidemiology Collaboration equation) in Latin American
      living donors. AIM: This study sought to determine whether there is correlation
      of the volume of the renal cortex by Herts equation with the GFR determined with
      renal gammagram (GFR-GR). PATIENTS AND METHODS: This was an analytical,
      observational, and cross-sectional study. A review of the donor charts from
      January 1, 2014, to December 1, 2014, with a complete clinical file, kidney
      measurements, predonation tomography volume, and eGFR by different formulas and
      by renal scintigraphy. RESULTS: Thirty-three donors were included, 51.5% male and
      48.5% female. The mean age was 38.58 +/- 10 years, with an average volume of
      127.83 +/- 28.30 mL, with diethylenetriamine-pentaacetate (DTPA) of 54.80 +/-
      7.13 mL/min/1.73 m2 in the donated kidney. Spearman correlation showed the best
      association with the Herts equation (r = 0.346) reaching significance (P = .049)
      when comparing the different equations against the GFR with DTPA. Using the Bland
      Altman method, the lowest variability and best significance was verified with the
      same equation compared to the other formulas (P = .0002). CONCLUSIONS: There is
      no consensus regarding which is the best formula for calculating the GFR of both
      kidneys. Of the different formulas, the one that best correlated with the GFR was
      the Herts method, which uses the volume of the kidney.

PMID- 29579821
TI  - Experience and Security of the Hand-Assisted Laparoscopic Nephrectomy of a Living
      Donor in a Public Health Center.
AB  - BACKGROUND: Hand-assisted laparoscopic nephrectomy (HALDN) is currently the
      procedure of choice for obtaining living donor kidneys for transplantation. In
      our institution, it has been the standard procedure for 5 years. Previous studies
      have shown the same function of the graft as that obtained by open surgery, with
      a lower rate of bleeding and no differences in complications. We sought to
      demonstrate the experience and safety of HALDN compared with open donor
      nephrectomy in healthy donors for kidney transplantation. METHODS: A
      retrospective analytical observational study was conducted, reviewing the records
      of the living donors for kidney transplant undergoing open donor nephrectomy or
      HALDN in our center from March 1, 2009, to March 1, 2016. Renal function was
      assessed by the estimated glomerular filtration rate by the Modification of Diet
      in Renal Disease method before and after donation, as well as bleeding (mL), and
      complications (according to Clavien), performing a comparative analysis between
      the two techniques using parametric or nonparametric tests. RESULTS: A total of
      179 living donor nephrectomies were performed during the study period-31 open
      donor nephrectomy (17.3%) and 148 HALDN (82.7%)-without relevant baseline
      differences, except for creatinine. HALDN has a shorter surgical time (156,473 +/
      87.75 minutes vs 165,484 +/- 69.95 minutes) and less bleeding (244.59 +/- 416.08
      mL vs 324.19 +/- 197.986 mL) and a shorter duration of hospital stay (3.74 +/-
      1.336 days vs 4.75 +/- 1.226 days). There were no significant differences in
      surgical complications at 30 days, or graft loss reported; there were 3
      conversions (1.7%) from the HALDN to the open technique. There were no
      differences in renal function in the donors or recipients at the 5th day or the
      month after surgery. CONCLUSIONS: Laparoscopic nephrectomy has replaced open
      surgery as the gold standard for living kidney donors. HALDN is a safe and
      feasible procedure when compared with open donor nephrectomy, achieving a shorter
      surgical time with less bleeding, and no difference in the number of
      complications. This procedure lowers costs by decreasing the duration of the
      hospital stay, making is feasible to perform it at any institution with
      appropriately trained personnel.

PMID- 29579822
TI  - Highly HLA Sensitized Kidney Transplant Patients in a Transplant Center.
AB  - INTRODUCTION: Approximately 10% to 30% of patients on renal transplant waiting
      lists are sensitized, which gives them more time on the waiting list.
      Transplantation in this setting has a greater risk of rejection and decreased
      graft survival. New strategies of donor allocation through virtual crossmatching
      and optimization of immunosuppressive therapies in induction and maintenance have
      allowed the allocation of organs for this population, which in other
      circumstances would not be chosen for a kidney transplant. OBJECTIVE: To describe
      the experience of renal transplantation in highly sensitized patients with a
      panel reactive antibody of >80% in a transplant center, through virtual
      crossmatching, discarding unacceptable antigens, and without desensitization
      treatment. METHODS: An observational, descriptive, retrospective case series
      study was conducted on highly sensitized kidney transplant patients with a panel
      reactive antibody of >=80% from 2010 to 2016. RESULTS: A total of 10 highly
      sensitized transplant patients were identified. Six patients were women, all of
      whom had a history of pregnancy; all patients had undergone blood transfusions,
      and 40% had undergone a first transplant. Average time spent on dialysis was
      148.5 months, and on the waiting list, 45.8 months. Average follow-up was 42
      months (range, 10-84 months). The estimated glomerular filtration rate by the
      Chronic Kidney Disease Epidemiology Collaboration method at year 1 was 75
      mL/min/1.73 m2 body surface. Nine patients at 1 year posttransplantation had
      graft and patient survivals of 100%, as did 5 patients at >3 years
      posttransplantation. CONCLUSIONS: Renal transplantation based on virtual
      crossmatching is a good alternative for highly sensitized patients.

PMID- 29579823
TI  - Impact of Clinical Simulation Training in Transplantation.
AB  - INTRODUCTION: The Hospital El Cruce is a high complexity center that performs
      transplants, both the procurement and the implant of organs and tissues. To deal
      with the low availability of organs and tissues from cadaveric donors it has been
      implemented the training through clinical simulation. OBJECTIVE: To assess if
      continuous training through procurement clinical simulation workshops modifies
      the production and quality indicators of organ and tissue procurement for
      transplantation in the hospital. MATERIALS AND METHODS: The workshop focuses on
      the procurement difficulties as detailed: workshops with high fidelity
      simulators: detection of potential donor; certification of death; treatment and
      selection of potential donor; workshops with role play actors; communication of
      the patient's death; and request for the last will of the deceased. A
      retrospective study was performed to compare between two periods the procurement
      activity. These periods defined 30-month before and after the opening of the
      workshop, as periods 1 and 2. RESULTS: In period 1, 44 patients underwent organ
      transplantation and 64 patients a tissue transplantation. After training through
      workshops (period 2), the number of patients increased to 71 for organ
      transplantation and 116 for tissue transplantation. CONCLUSIONS: Assessment of
      the two periods indicates that the production and quality indicators of organ and
      tissue procurement improved in the second period. Continuous training through
      procurement clinical simulation workshops is highlighted within all tasks carried
      out in the hospital. Clinical simulation is a motivating factor for the
      development of this activity in the hospital.

PMID- 29579824
TI  - Peripheral Blood Regulatory T Cells Are Diminished in Kidney Transplant Patients
      With Chronic Allograft Nephropathy.
AB  - BACKGROUND: Our aim in this study was to assess peripheral blood CD4+CD25+FOXP3+
      regulatory T cell (Treg) levels in patients with chronic allograft nephropathy
      (CAN) 1 year after kidney transplantation. METHODS: Twelve renal transplant
      patients with an initial onset of CAN, 12 patients with chronic kidney disease
      (CKD) stage G5 on dialysis, and 13 healthy control individuals were evaluated
      regarding the proportion of Tregs in their peripheral blood via flow cytometry.
      RESULTS: The renal transplant patients with CAN had a significantly lower
      proportion of Tregs than the hemodialysis CKD patients and healthy controls (P <
      .0001). In contrast, the hemodialysis CKD patients showed higher levels of Tregs
      than the renal transplant patients with CAN and the healthy controls (P < .0001).
      CONCLUSION: The high level of peripheral blood Tregs in the hemodialysis CKD
      patients suggests a chronic inflammatory state. However, the low frequency of
      Tregs in the peripheral blood from the renal transplant patients with CAN
      suggests an unfavorable prognosis for allograft immune tolerance.

PMID- 29579825
TI  - Renal Transplantation in Second-Level Private Hospitals in the State of Mexico.
AB  - BACKGROUND: Kidney transplantation (KT) is the replacement therapy of choice in
      patients with end-stage renal disease (ESRD). Here we show a cohort of kidney
      transplant recipients from the period of May 1994 to May 2016 in 2 2nd-level
      private hospitals from the city of Toluca in the state of Mexico. METHODS: We
      checked the clinical files of all the patients that received KT in the period of
      study. RESULTS: We report 25 KT: 23 performed in Sanatorio Toluca and 2 in
      Sanatorio Florencia; 16 (64%) male and 9 (26%) female; mean age 36.03 +/- 15.9
      years (range, 10-66); 19 (76%) hemodialysis and 9 (24%) continuous ambulatory
      peritoneal dialysis before KT; ESRD etiology unknown in 16 (64%), diabetes in 5
      (20%), IgA nephropathy in 2 (8%), and other in 2 (8%); living donors in 13 (52%)
      and deceased donors in 12 (48%); blood group 0+ in 18 (72%), A+ in 5 (20%), and
      B+ in 2 (8%); 21 (84%) with 0 and 4 (16%) with 1 HLA mismatch; and delayed graft
      function in 8 (32%), of which 7 were from deceased donors and 1 from a living
      donor. All 25 (100%) had a functional kidney at 1 year of follow-up.
      Immunosuppression regime consisted of multitarget maintenance therapy in all 25
      (100%): cyclosporine in 18 (72%) and tacrolimus in 7 (28%). We used only
      methylprednisolone (MTP) as induction therapy. There were only 2 cases (8%) of
      acute rejection during the 1st 6 months of follow-up, and both responded to
      treatment with MTP. CONCLUSIONS: KT is the treatment of choice for patients with
      ESRD. The obtained results using only an MTP induction regime are satisfactory,
      with graft and patient survivals of 100% in the 1st year of follow-up.

PMID- 29579826
TI  - Cardiac Remodeling in Structure and Function Six Months After Kidney
      Transplantation.
AB  - BACKGROUND: Cardiovascular disease accounts for 35% to 50% of the causes of
      mortality in chronic kidney disease. The majority of patients in substitution
      therapy in Mexico are subdialyzed owing to limited economic resources. This
      produces more cardiac deterioration than described in the statistics and has a
      direct impact on the prognosis of kidney transplantation. The aim of this work
      was to demonstrate and to quantify the improvement in the echocardiographic
      parameters 6 months after renal transplantation in patients with stable renal
      function. METHODS: This was an observational, analytic, prospective study of 23
      patients with chronic kidney disease who received transplants in 2016 and had a
      glomerular filtration rate >=80 mL/min (Chronic Kidney Disease-Epidemiology
      Collaboration) 6 months after transplantation. RESULTS: Echocardiographic results
      showed an increase in the left ventricular ejection fraction from 57.17 +/-
      10.46% to 64.09 +/- 9.8%, an increase in the right ventricular ejection fraction
      from 0.56 +/- 0.09% to 0.60 +/- 0.08% and a reduction of the pulmonary arterial
      systolic pressure from 44.57 +/- 13.88 mm Hg to 39.74 +/- 11.04 mm Hg. There were
      also decreases in mitral regurgitation from 1.0 to 0.43, tricuspid insufficiency
      from 1.35 to 0.43, pulmonary insufficiency from 0.48 to 0.04, and aortic
      insufficiency from 0.35 to 0.04, all of these significant with P < .05.
      CONCLUSIONS: There was a significant improvement in cardiovascular function in
      our population 6 months after transplantation, despite the fact that renal
      transplantation is performed with greater cardiac deterioration than described in
      patients in other countries.

PMID- 29579827
TI  - Epidemiologic Study and Genotyping of BK Virus in Renal Transplant Recipients.
AB  - BK virus (BKV) infection occurs during childhood and remains latent in the
      urinary tract. The virus is reactivated in immunosuppressed patients,
      particularly in those with cellular immunity deficiency, allowing its detection
      in urine and blood. Nephropathy caused by the virus in renal transplantation
      recipients may lead to graft failure. The purpose of this study is to know the
      prevalence of BKV variables in renal transplantation recipients and to evaluate
      their clinical evolution through molecular methods of "in house" development.
      Urine and peripheral blood samples from 66 renal transplantation recipients from
      the province of Buenos Aires, Argentina, were systematically analyzed every 3
      months as well as when there was graft dysfunction. Renal biopsies, which were
      included in the BKV detection study, were performed on those patients with graft
      dysfunction. Genotyping of 24 BKVs was performed, and the following distribution
      was found: 21 (87.5%) belonged to subtype I, 3 (12.5%) to subtype II. BKV
      belonging to subtypes III or IV were not found. As regards subtype I subgroups,
      the following were identified: 1 (4.76%) from Ia, 10 (47.61%) from Ib1 and 10
      (47.61%) from Ib2. Presence of subgroup Ic was not shown. Viremia presented in
      33.33% of cases, whereas 75% corresponded to subgroup Ib 1. Genotype Ib1 is
      prevailing in Southeast Asia, while Ib2 is prominent in Europe. Although an
      important proportion of the inhabitants of the province of Buenos Aires are
      European descendants, the prevailing genotype is Ib1, the Asian type. Genotyping
      might be related to the evolution of the disease in the recipient.

PMID- 29579828
TI  - Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.
AB  - BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant
      patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory
      drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been
      reported. This study assesses the effect, safety, and possible drug interactions
      in kidney transplant patients treated with CBD for chronic pain. METHODS: We
      assessed patients who asked to receive CBD for pain treatment. Doses were
      increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count,
      liver function, liver enzymes, and drug levels were determined every 48 hours the
      first week and then once a week thereafter. RESULTS: We assessed 7 patients with
      a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD
      dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent
      nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and
      21 owing to persisting elevated levels (even before CBD) and itching, and on day
      21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the
      control 1 week later. Patients on cyclosporine were stable. Adverse effects were
      nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD
      dose decrease was required in 2 patients. Two patients had total pain
      improvement, 4 had a partial response in the first 15 days, and in 1 there was no
      change. CONCLUSIONS: During this follow-up, CBD was well-tolerated, and there
      were no severe adverse effects. Plasma levels of tacrolimus were variable.
      Therefore, longer follow-up is required.

PMID- 29579829
TI  - Mortality Analysis of Acute Liver Failure in Uruguay.
AB  - BACKGROUND: Acute liver failure (ALF) is a syndrome with high mortality.
      OBJECTIVE: Describe characteristics and outcomes of patients with ALF in Uruguay,
      and identify factors associated with mortality. METHODS: A retrospective analysis
      of 33 patients with ALF was performed between 2009 and 2017. RESULTS: The
      patients' median age was 43 years, and 64% were women. Average Model for End
      Stage Liver Disease (MELD) score at admission was 33. The median referral time to
      the liver transplant (LT) center was 7 days. The most common etiologies were
      viral hepatitis (27%), indeterminate (21%), autoimmune (18%), and Wilson disease
      (15%). Overall mortality was 52% (71% of transplanted and 46% of nontransplanted
      patients). Dead patients had higher referral time (10 vs 4 days, P = .008),
      higher MELD scores at admission (37 vs 28) and highest achieved MELD scores (42
      vs 29; P < .001), and higher encephalopathy grade III to IV (94% vs 25%, P <
      .001) than survivors. Patients without LT criteria (n = 4) had lower MELD score
      at admission (25 vs 34, P = .001) and highest achieved MELD score (27 vs 37, P =
      .008) compared with the others. Patients with LT criteria but contraindications
      (n = 7) had higher MELD scores at admission (38 vs 31, P = .02), highest achieved
      MELD scores (41 vs 34, P = .03), and longer referral time (10 days) than those
      without contraindications (3.5 days) or those without LT criteria (7.5 days, P =
      .02). Twenty-two patients were listed; LT was performed in 7, with a median time
      on waiting list of 6 days. CONCLUSIONS: ALF in Uruguay has high mortality
      associated with delayed referral to the LT center, MELD score, and
      encephalopathy. The long waiting times to transplantation might influence
      mortality.

PMID- 29579830
TI  - Acute Liver Failure-25 Years at a Single Center: Role of Liver Transplantation in
      the Survival of Adult Patients.
AB  - BACKGROUND: Acute liver failure (ALF) leads to high morbidity and mortality and
      is characterized by an accelerated deterioration of hepatic function in patients
      without prior liver disease. The survival rate is <15% without liver
      transplantation (LT). The aim of this study was to describe the population of
      patients with ALF in the Unit of Liver Transplantation of the University of
      Campinas, Brazil, from 1991 to 2017, comparing those submitted and not submitted
      to LT. METHODS: The patients were divided into 2 groups: 1, listed but not
      transplanted; and 2, transplanted. RESULTS: There were 73 patients with ALF
      listed for LT, with a mean age of 33.6 years, 49 (67.1%) female and 24 (32.9%)
      male. Group 1, with 32 patients, had a mean age of 29.3 years; 26 (81.25%) died
      on the waiting list; 6 (8.45%), with a mean age of 12.33 years, were removed from
      the list because of recovery of liver function. Considering only adult patients,
      the mortality without LT was 96.29%. Group 2 had 41 patients, with a mean age of
      37.1 years, and a 30-day survival of 41.02%. Thus, LT led to a significant
      improvement in the survival of adult patients with ALF. The time of surgery,
      packed red blood cells, and intraoperative plasma, were associated with LT
      survival after logistic regression study, whereas age, body mass index,
      bilirubin, international normalized ratio, creatinine, sodium, and Model for End
      Stage Liver Disease score were not. CONCLUSIONS: ALF affects an active age range,
      and LT decreases mortality; there was no good preoperative prognostic indicator
      to assess which patients would benefit from transplantation.

PMID- 29579831
TI  - Acute Liver Failure Induced by Carthamus tinctorius Oil: Case Reports and
      Literature Review.
AB  - BACKGROUND: Acute liver failure (ALF) is a clinical syndrome that results from
      the abrupt loss of liver function in a patient without previous liver disease.
      The most frequent causes are viral hepatitis, drug induced, and autoimmune
      disease, but in 20% of cases no cause is identified. Carthamus tinctorius
      (safflower) oil is used as a dietary supplement for weight loss and antioxidant.
      There are 4 cases described in the literature of ALF induced by the use of this
      substance. The objective of this study was to report 3 cases of ALF treated at
      the Clinical Hospital of the State University of Campinas that suggest the use of
      C tinctorius oil as a probable etiologic factor. CASE REPORTS: The 3 patients had
      a diagnosis of ALF according to the King's College criteria. All had a history of
      ingestion of this oil for weight loss. During etiologic evaluation, viral
      hepatitis, autoimmune diseases, or any other drug cause were excluded, thus
      pointing to C tinctorius oil as the triggering factor. All 3 patients underwent
      liver transplantation: 2 had good postoperative evolution, and 1 died 12 days
      after the procedure. CONCLUSIONS: Two cases are described in which the hepatic
      insufficiency induced by C tinctorius oil was successfully treated through liver
      transplantation. This highlights the risk of misuse of this substance for weight
      loss.

PMID- 29579832
TI  - Characteristics of Liver Transplantation in Argentina: A Multicenter Study.
AB  - INTRODUCTION: There is a lack of information regarding outcomes after liver
      transplant in Latin America. OBJECTIVES: This study sought to describe outcomes
      after liver transplant in adult patients from Argentina. METHODS: We performed an
      ambispective cohort study of adult patients transplanted between June 2010 and
      October 2012 in 6 centers from Argentina. Only patients who survived after the
      first 48 hours postransplantation were included. Pretransplantation and
      posttransplantation data were collected. RESULTS: A total of 200 patients were
      included in the study. Median age at time of transplant was 50 (interquartile
      range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the
      most frequent etiology in these patients was hepatitis C (32%). A total of 35
      (17%) patients were transplanted with hepatocellular carcinoma. In patients with
      cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of
      liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for
      elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for
      urgent patients. Almost 40% of the patients were readmitted during the first 6
      months after liver transplant. Acute rejection occurred in 27% of the patients.
      Biliary and vascular complications were reported in 39 (19%) and 19 (9%)
      patients, respectively. Renal failure, diabetes, and dyslipidemia were present in
      40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We
      believe the information contained in this article might be of value for reviewing
      current practices and developing local policies.

PMID- 29579833
TI  - Tumor Biology as Predictor of Mortality in Liver Transplantation for
      Hepatocellular Carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant
      liver tumor, with the Milan criteria considered to be the gold standard for
      patient selection for liver transplantation (LT). MATERIALS AND METHODS: We
      performed a descriptive observational study, reviewing 20 years of experience of
      LT in patients with HCC in the Fundacion Valle del Lili in Cali, Colombia.
      Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015.
      RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In
      the first period patients within the Milan criteria had a recurrence-free
      survival at 5 years of 66.6%, and in those who exceeded the Milan criteria,
      recurrence-free survival was 75%. In the second period, patients within the Milan
      criteria, recurrence-free survival at 5 years was 93.5%, and in those who
      exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically
      significant difference was found in either period. For patients with mild and
      moderate tumor differentiation, the relapse survival rate at 5 years was 69.4%
      (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90),
      respectively. All patients with poor tumor differentiation relapsed and died
      within 3 years. CONCLUSION: Global and recurrence-free survival among patients
      who met and patients who exceeded the Milan criteria was not significantly
      different, suggesting an expansion of the Milan criteria to include potential
      recipients who were previously excluded. Obtaining histologic differentiation and
      identifying vascular invasion will provide a more worthwhile contribution to LT
      decision making.

PMID- 29579834
TI  - Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South
      American Transplant Center.
AB  - BACKGROUND: Around 2.4% of the world's population is infected with hepatitis C
      virus (HCV), and it is the most common cause of liver transplantation (LT) in the
      world. Latin America (LA), with nearly 9% of the world population, has had a
      continuous increase in the number of LTs per year. Yet, due to the lack of
      mandatory data collection and a well-developed health-care system, access to
      transplantation is limited in most LA countries. We report the first LA
      experience of HCV-infected LT patients. METHODS: We performed a retrospective
      cohort study by reviewing the medical histories of all HCV-infected LT patients
      between 1996 and 2016 who acquired HCV before their LT, at the Fundacion Valle
      del Lili, Cali, Colombia. RESULTS: Between January 1996 and December 2015, a
      total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV
      infection. With a median follow-up time of 24.4 months (interquartile range [IQR]
      4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996
      2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in
      30.6% of the patients, and overall postoperative complications had an incidence
      of 80%. CONCLUSIONS: This is the first report of LT in HCV-infected patients in
      Colombia and in LA. Our results are comparable to those of other transplant
      centers worldwide with regard to postoperative complications and patient
      survival. Patients with LT in the 1996-2006 time frame had higher morbidity and
      mortality. Studies including larger numbers of patients are needed to determine
      the reason for this finding.

PMID- 29579835
TI  - Risk Factors of Mortality After Liver Transplantation in Uruguay.
AB  - INTRODUCTION: Identification of predictive factors of mortality in a liver
      transplant (LT) program optimizes patient selection and allocation of organs.
      OBJECTIVE: To determine survival rates and predictive factors of mortality after
      LT in the National Liver Transplant Program of Uruguay. METHODS: A retrospective
      study was conducted analyzing data prospectively collected into a
      multidisciplinary database. All patients transplanted since the beginning of the
      program on July 2009 to April 2017 were included (n = 148). Twenty-nine factors
      were analyzed through the univariate Kaplan-Meier model. A Cox regression model
      was used in the multivariate analysis to identify the independent prognostic
      factors for survival. RESULTS: Overall survival was 92%, 87%, and 78% at
      discharge, 1 year, and 3 years, respectively. The Kaplan-Meier survival curves
      were significantly lower in: recipients aged >60 years, Model for End-Stage Liver
      Disease score >21, LT due to hepatocellular carcinoma (HCC) and acute liver
      failure (ALF), donors with comorbidities, intraoperative blood loss beyond the
      median (>2350 mL), red blood cell transfusion requirement beyond the median
      (>1254 mL), intraoperative complications, delay of extubation, invasive
      bacterial, and fungal infection after LT and stay in critical care unit >4 days.
      The Cox regression model (likelihood ratio test, P = 1.976 e-06) identified the
      following independent prognostic factors for survival: LT for HCC (hazard ratio
      [HR] 4.511; P = .001) and ALF (HR 6.346; P = .004), donors with comorbidities (HR
      2.354; P = .041), intraoperative complications (HR 2.707; P = .027), and invasive
      fungal infections (HR 3.281; P = .025). CONCLUSION: The survival rates of LT
      patients as well as the mortality-associated factors are similar to those
      reported in the international literature.

PMID- 29579836
TI  - Early Bacterial Pneumonia After Hepatic Transplantation: Epidemiologic Profile.
AB  - BACKGROUND: Postoperative pulmonary complications are major cause of morbidity
      and mortality in patients receiving liver transplantation (LT), particularly
      bacterial pneumonia occurring within the first 100 days after transplantation.
      Our aim in this study was to determine the incidence, microorganisms involved,
      associated factors, and morbidity of bacterial pneumonia presenting in the first
      100 days posttransplant. METHODS: We performed a cohort study in which patients
      receiving liver transplantation were included prospectively in our national
      database (Database of Infections in Transplantation of Solid Organs). The study
      period was from July 14, 2009 to July 24, 2015. RESULTS: One hundred six patients
      were transplanted during the 6-year period. We documented 9 bacterial pneumonia
      cases with an incidence of 8.5 per 100 patients; 2 patients had hospital-acquired
      pneumonia (HAP) and 7 had ventilator-associated pneumonia (VAP). In 4 of the 9
      bacterial pneumonia cases, patients presented with bacteremia. Eleven
      microorganisms were isolated these 9 patients. Microbiologic diagnosis methods
      included 5 cases of alveolar bronchoalveolar lavage (BAL), 1 case of BAL and
      pleural fluid puncture, 1 case of pleural fluid puncture, and 1 case through
      sputum study. Of the 11 isolated organisms, 9 corresponded to Gram-negative
      bacilli (GNB): Klebsiella spp, n = 3; Acinetobacter baumannii, n = 4; Morganella
      morganii, n = 1; and Pseudomonas aeruginosa, n = 1. Regarding the resistance
      profile, 7 presented with a multiresistance profile (MDR) and extreme resistance
      (XDR). Univariate analysis identified the Model for End-Stage Liver Disease
      (MELD) pretransplant score as a factor associated with developing pneumonia (P <
      .001, 95% confidence interval [CI] 2.872-10.167), and early extubation, before 8
      hours posttransplant, as a protective factor (P = .008; relative risk [RR] 0.124;
      95% CI 0 .041-0.377). Hospital stay was longer in patients with pneumonia
      compared to those without pneumonia (P < .0001, 95% CI 17.79-43.11 days). There
      was also an increased risk of death in patients with pneumonia (RR 17.963; 95% CI
      5106-63,195). CONCLUSIONS: Early bacterial pneumonia after hepatic
      transplantation is associated with higher morbidity and mortality. At our center,
      4 of 9 patients had bacteremia. GNB cases with MDR and XDR profiles are
      predominant. Early extubation is a protective factor.

PMID- 29579837
TI  - Corneal Donor Profile and Evolution of Corneal Donation in a Brazilian State
      Where the Number of Individuals on the Waiting List Reached Zero But Increased
      Again.
AB  - BACKGROUND: In most countries, the amount of corneal graft tissue available for
      transplantation is insufficient to meet demand. In 2010, there were 459 patients
      on the waiting list for corneal transplantation (WLCT) in Espirito Santo (ES), a
      Brazilian state with 3,885,000 inhabitants. Several strategies were implemented
      to reduce the number of individuals on the WLCT, which reached zero in 2011.
      Studies on the evolution of corneal donation contribute to reducing the WLCT
      worldwide. The aim of this study was to describe the evolution of corneal
      donation in ES and the profile of corneal donors from 2010 to 2013. METHODS: This
      was a retrospective study. The data were collected from records referring to
      donations of corneas and from the archives of the Center for Organ Procurement
      and Distribution of ES. Statistical software was used to perform descriptive
      analysis of the data. RESULTS: The sample consisted of 1359 donors, aged 46.82 +/
      17.32 (mean +/- standard deviation), 70.1% of whom were male. Most of the
      consent forms for donation were signed by the sons of the donors. In 2011, there
      was a major increase (105%) in the number of corneal transplants compared with
      2010; consequently, the number of patients on the WLCT reached zero, but
      increased again, reaching 139 patients in 2013. CONCLUSION: This study shows that
      strategies to increase corneal donations should be continued even after reduction
      or elimination waiting time on the WLCT.

PMID- 29579839
TI  - The 10th Congress of the Andalusian Society of Organ and Tissue Transplantation
      (SATOT).

PMID- 29579838
TI  - Endoscopic Treatment for Vesicoureteral Reflux in Recurrent Urinary Tract
      Infections in Kidney Transplant: Experience of One Center.
AB  - Vesicoureteral reflux (VUR) after renal transplantation in adult patients has
      been reported. In renal transplant recipients, symptomatic urinary tract
      infection can cause high morbidity despite improved immunosuppressive and
      antibiotic treatment. In our country there have been few reported cases about use
      of copolymer of dextranomer and hyaluronic acid (DX-HA) injection in a renal
      transplant. We present 3 cases of recurrent or complicated infections with
      evidence of high-grade VUR, which were treated with DX-HA. Only 1 case had a
      partial remission; however, there were no episodes of urinary tract infection in
      12 months of follow-up. Suburethral injection is an endoscopic treatment modality
      with low morbidity in our country.

PMID- 29579840
TI  - Teenagers in Rural Areas Faced With Organ Donation and Transplantation.
AB  - INTRODUCTION: In rural areas it is common to find unfavorable attitudes toward
      organ donation, and therefore it is important to find out the attitude and
      profile of new generations for improving predisposition to organ donation in
      these areas. Our objective was to analyze the attitude toward organ donation and
      the related variables of teenagers in a rural area. MATERIALS AND METHODS:
      Students in the final year of compulsory education (mostly 15-16 years of age)
      were selected from secondary schools in a rural area in southeastern Spain (n =
      319; population density <300 inhabitants/km2). The instrument of measurement used
      was a validated psychosocial questionnaire. Completion was anonymous and self
      administered. Descriptive statistical analysis, Student t test, chi2 test, and
      multivariate analysis were employed. RESULTS: There was a completion rate of 96%
      (n = 306). Overall, 65% (n = 200) were in favor of donating their organs, 30% (n
      = 90) were undecided, and 5% (n = 16) were against. Attitude toward the donation
      of one's own organs was related with sex (P = .015), previous experience of organ
      donation or transplantation (P = .046), comment on the topic of organ donation
      within the family (P = .003; odds ratio 2.155), knowing one's mother's opinion
      about the matter (P = .021), knowing the correct concept of brain death (P =
      .012; odds ratio 2.076), and religion (P = .014). CONCLUSIONS: A favorable
      attitude of teenagers in rural areas toward organ donation is slightly higher
      than in the adult population and is determined by many psychosocial variables,
      above all family discussion about organ donation and transplantation and correct
      knowledge of the brain death concept.

PMID- 29579841
TI  - Importance for the Elderly of Discussion in the Family and Society About Attitude
      Toward Organ Donation.
AB  - BACKGROUND: The aging of the population has changed some of the approaches to the
      organ donation and transplant (ODT) process, such as considering elderly people
      as potential donors. We aimed to assess social and family discussions among the
      elderly about ODT and its effect on their attitude toward organ donation.
      METHODS: A study was carried out at 2 publicly-funded social centers for the
      elderly. Contact was made with individuals >65 years of age (n = 120) to seek
      their participation in the study. A questionnaire was distributed to them with
      questions about ODT. A descriptive assessment was performed with the Student t
      test and chi2 test used for statistical analysis. RESULTS: The completion rate
      was 87% (n = 104). Of the respondents with a partner and children, 48% had
      discussed the topic of ODT. It was found that talking about the subject with
      one's partner, children, or friends had a favorable influence on attitude
      compared with when this was not done (93%, 86%, and 83% vs 19%, 30%, and 31%,
      respectively; P < .001). In addition, the opinion of one's partner and children
      toward ODT also had an influence; if favorable, the respondent's attitude was
      more favorable, compared with when they did not know their opinion (92% to 88% vs
      58% to 37%, respectively; P < .001). Other ODT-related variables did not affect
      their attitude (P > .05). CONCLUSIONS: Almost half of the elderly people had
      discussed ODT socially or with their family. This discourse has a favorable
      influence on their attitude toward organ donation and, therefore, it is important
      to encourage social and family dialog among this group.

PMID- 29579842
TI  - Teenagers and Their Future Role in Transplantation: An Analysis of Their
      Attitudes Toward Solid Organ Xenotransplantation.
AB  - INTRODUCTION: It is important to determine the level of social acceptance of
      xenotransplantation, especially in places where there are preclinical
      xenotransplantation projects. In this sense, it is important to know the attitude
      of teenagers, given that their attitude could have an influence on this kind of
      donation in the future. OBJECTIVES: The aim of this study is to analyze the
      attitudes of teenagers toward xenotransplantation and to determine the variables
      affecting their attitudes. MATERIAL AND METHODS: A random simple was obtained of
      students who were between 12 and 16 years of age in secondary schools in the
      southeast of Spain (n = 3633). Their attitudes were assessed with the use of a
      validated psychosocial questionnaire about xenotransplantation (PCID-XenoTx
      Rios). The questionnaire was completed anonymously and was self-administered.
      Descriptive statistical analysis, Student t, and chi2 tests were used. RESULTS:
      The completion rate was 97% (n = 3531). With regard to animal organ donation for
      humans, 44% (n = 1569) would be in favor, 22% (n = 784) against, and 34% (n =
      1178) undecided. Attitude was related to knowing a transplantation patient (P =
      .02), believing that transplant organ needs are not covered (P = .004), having
      received information about organ donation and transplantation (ODT) on television
      and from schools (P = .001), family discussion about ODT (P < .001), attitude of
      the respondent's parents (P < .001), and attitude toward human donation (P <
      .001). CONCLUSIONS: More than half of the teenagers had unfavorable attitudes
      toward xenotransplantation as this was determined by factors related to knowledge
      of and previous information about ODT, the attitude of one's family, and
      attitudes toward the different types of human organ donation.

PMID- 29579843
TI  - Short-term Results From a Training Program to Improve Organ Donation in
      Uncontrolled Donation After Circulatory Death.
AB  - BACKGROUND: In all organ transplantation programs, election of the proper
      protocol relies primarily on the professionals involved in the detection of
      potential donors. The objective of our study was to assess the impact of a series
      of prehospital training sessions, as well as to develop several positive feedback
      strategies within the uncontrolled organ donation after circulatory death (uDCD)
      program in our city. METHODS: A before-after intervention study was carried out
      in 3 steps. First, professionals enrolled in the Emergency Health Services Agency
      061 (EPES-061) program underwent specific training to identify potential donors.
      Second, a specific logotype was designed to alert emergency health care
      professionals that in cases where cardiopulmonary resuscitation was ineffective
      and after treatment of all potentially reversible causes, the "chain of survival"
      should be considered a "chain of opportunities." Third, a positive feedback
      strategy was put in place, whereby each time a donation was procured, the EPES
      061 personnel that had identified the potential donor were notified by phone and
      in a personal letter. RESULTS: The mean age for donors was 50.5 years of age
      (interquartile range 37-52.5), and 89.5% of all donations came from male
      subjects. Positive feedback letters and phone calls, including information on
      final outcome, were provided to the appropriate personnel in 100% of the cases.
      Postintervention information showed an increase in both eligible and utilized
      donors. CONCLUSIONS: Interventions outside the hospital setting that facilitate
      optimal implementation of the uDCD program are an essential part of this strategy
      to increase the donor pool and make the wait shorter for transplant patients.

PMID- 29579844
TI  - Postoperative Care in Kidney Transplantation: A Comparison Between Controlled and
      Uncontrolled Donation After Circulatory Death.
AB  - Recent research in kidney transplantation has revealed differences in the
      evolution of renal function among patients transplanted from 2 alternative
      programs for donation after circulatory death (DCD). A retrospective,
      observational, single-center study was carried out from 2013 to 2016 at a level
      III hospital intensive care unit (ICU) to assess the progression of kidney
      recipients after transplants from uncontrolled DCD (uDCD) or controlled DCD
      (cDCD). The following variables were collected for data analysis: demographics,
      comorbidities, type of donation, lactate, hemoglobin and glucose levels at ICU
      admission, creatinine concentration at ICU admission, at-hospital ward transfer,
      at-hospital discharge, radioisotope imaging results, ICU and in-hospital length
      of stay, and mortality. There were 87 patients eligible for analysis, 42.5% of
      which were uDCD recipients. Improvement in kidney function was significantly
      delayed after uDCD compared with cDCD. A multivariate analysis showed that both
      uDCD and lactate levels at ICU admission increase the risk of poor outcome after
      renal transplantation. No deaths were registered in either patient group. Our
      results suggest that kidney transplantation recipients from uDCD recover renal
      function at a slower rate than patients transplanted from cDCD, a factor that
      does not affect mortality.

PMID- 29579845
TI  - Results of Controlled Donation After Circulatory Death in a Third-Level Hospital.
AB  - OBJECTIVE: To investigate the characteristics and evolution of controlled
      donation after circulatory death (DCD) type III. MATERIALS AND METHODS:
      Observational and retrospective study of controlled DCD type III of donors
      conducted from 2014 to 2016. Clinical data, intensive care unit (ICU) stay, cause
      of death, warm ischemia time, and total time were collected. Delayed graft
      function (DGF) and survival of renal transplant were also registered. Qualitative
      variables are described as frequencies and absolute values and quantitative
      variables as medians and interquartile ranges. RESULTS: A total of 21 donors were
      collected; 71% (15) were males, median age was 55 years (interquartile range [IR]
      48-72), and median ICU stay was 7 days (IR 4-12). The main cause of death was
      anoxic encephalopathy (57%, 12), followed by intracerebral hemorrhage (28%, 6).
      In 48%, withdrawal of life support occurred in the operating room, and 98% of
      donors were preserved by abdominal super-rapid cannulation technique. Average
      warm ischemia time was 20 minutes (IR 16-24), and total ischemia time was 26
      minutes (IR 23-34). Of the donations, 57% were livers and 90% were kidneys. Out
      of 42 kidneys donated, 54% (23) of them were valid. Median renal transplant
      hospital stay was 18 days (IR 6-24), and 46% develop DGF. Survival at discharge
      was 100%. CONCLUSION: DCD type III ensures a source of organs. The main cause of
      death was anoxic encephalopathy. Most donors were able to donate some solid
      organ.

PMID- 29579846
TI  - Combined Flush With Histidine-Tryptophan-Ketoglutarate and University of
      Wisconsin Solutions in Liver Transplantation: Preliminary Results.
AB  - INTRODUCTION: Ischemia reperfusion injury (IRI) is the main cause of early
      allograft dysfunction (EAD) and subsequent primary allograft failure (PAF).
      OBJECTIVES: The purpose of this study is to compare IRI, EAD, and PAF in liver
      transplantation in a cohort of patients perfused with histidine-tryptophan
      ketoglutarate (HTK) solution and University of Wisconsin (UW) solution versus HTK
      alone. METHODS: A randomized trial was performed to compare outcomes in liver
      recipients who underwent transplantation surgery in the University Regional
      Hospital of Malaga, Spain. Forty patients were randomized to two groups. Primary
      endpoints included IRI, EAD, PAF, re-intervention, acute cellular rejection,
      retransplantation, arterial complications, and biliary complications at
      postoperative day 90. RESULTS: Postoperative glutamic oxaloacetic transaminase
      (1869.15 +/- 1559.75 UI/L vs. 953.15 +/- 777.27 UI/L; P = .004) and glutamic
      pyruvic transaminase (1333.60 +/- 1115.49 U/L vs. 721.70 +/- 725.02 U/L; P =
      .023) were significantly higher in patients perfused with HTK alone. A clear
      tendency was observed in recipients perfused with HTK alone to present moderate
      to severe IRI (7 patients in the HTK + UW solution group vs. 15 patients in the
      HTK-alone solution group; P = .06), EAD (0 patients in the HTK + UW solution
      group vs. 0 patients in the HTK-alone solution group; P = .76), and PAF (3
      patients in the HTK + UW solution group vs. 8 patients in the HTK-alone solution
      group; P = .15). CONCLUSIONS: Initial perfusion with HTK solution followed by UW
      solution in liver transplantation improves early liver function as compared to
      perfusion with HTK alone.

PMID- 29579847
TI  - Living Donor in Renal Transplantation: Minimizing Risks.
AB  - In recent years, the broadening of indications for renal transplantation,
      together with the progressive reduction of donations following brain stem death,
      has led to living donation being considered in increasing numbers of cases for
      renal transplantation. To investigate this further, it is necessary to assess the
      impact it has on the postoperative outcomes in the intensive care unit (ICU). Our
      group conducted a retrospective, observational, single-center study from 2013 to
      2016 to evaluate differences in outcomes between living and cadaveric kidney
      donation both during ICU admission and total hospitalization. We compared
      differences in characteristics between living and deceased graft recipients
      including demographics, comorbidities, analytical data, radioisotope imaging test
      results, complications, ICU and hospital ward length of stay, and mortality. In
      all, 387 patients were eligible for analysis, and 13% received living donor
      grafts. Our results demonstrate that this group had significantly fewer
      complications, shorter length of hospital stay, and reduced mortality in
      comparison with recipients of cadaveric donor grafts. The better postoperative
      outcomes from living donor grafts could result from careful selection of the
      donor and less inflammatory injury, minimizing risk in the postoperative period.

PMID- 29579848
TI  - Anti-HLA Antibodies After Precocious Transplantectomy by Vascular Thrombosis.
AB  - BACKGROUND: Our objective in this study was to determine the effects of early
      renal transplantectomy on patients and the production of anti-human leukocyte
      antigen (anti-HLA) antibodies. METHODS: Between January 2003 and May 2017, we
      analyzed a group of patients for the presence of specific HLA class I and/or II
      donor-specific antibodies (DSA), their panel-reactive antibodies (PRA), and the
      time period in which the antibodies were still detectable after transplantectomy.
      RESULTS: Anti-HLA antibodies were detected in 60.8% of patients, 60.8% and 52.2%
      of those patients had anti-class I and anti-class II antibodies, respectively.
      DSA were detected in 91.7% of the anti-HLA class I patients. Class II DSA were
      detected all of the patients with anti-HLA class II antibodies. The average (mean
      +/- SD) PRA levels in our patients after transplantectomy was 60 +/- 34% in class
      I and 63 +/- 36% in class II. CONCLUSION: Anti-HLA antibodies can be detected
      well after transplantectomy. Even if the kidney allograft had been transplanted
      for only a short time, when the intensity of immunosuppression was the highest,
      many patients developed anti-HLA antibodies. The patients who continued with
      immunosuppression after transplantectomy did not develop anti-HLA antibodies.

PMID- 29579849
TI  - Local Variation in Inclusion on Kidney Transplant Waiting Lists: Analysis in the
      Reference Area of a Kidney Transplant Center.
AB  - BACKGROUND: Access for end-stage renal disease (ESRD) patients to the renal
      transplant (RT) waiting list can vary depending on the criteria used and how they
      are applied in each dialysis unit. METHODS: This study was performed in the
      reference area (2.5 million inhabitants) of a transplant center. Data were from a
      regional registry (Information System of the Autonomous Coordination of
      Transplants in Andalusia) of total dialysis patients. Patients were grouped
      according to transplant status as: effective waiting list (WL); never recorded or
      excluded (E); incomplete immunologic study or discharge data (IIS); temporary
      contraindication (TC); or active (A). RESULTS: There were 1424 dialysis patients.
      Of these, 58% were E, 18% were IIS, 14% were TC, and 10% were A. Significant
      differences were detected for proportion of patients listed as active status (A)
      in 3 hospital dialysis units (2.9%-13.4%) and 12 hemodialysis centers (4.2%
      29.2%); proportion of IIS cases in the hospitals (0%-57%) and dialysis centers
      (0%-58%); and in proportion of TC cases in the hospitals (19%-50%) and dialysis
      centers (2.5%-19.3%). The mean age of patients varied significantly between IIS,
      TC, and A groups (60.3, 54.8, and 52.3 years old, respectively, P < .001).
      Accentuated differences between the 2 provinces included in the sector were
      verified. There are notable differences in inclusion of pre-dialysis patients
      between hospital units. CONCLUSION: We detected considerable variability between
      hospital units and non-hospital dialysis centers in relation to inclusion on the
      active transplant waiting list and the proportion of patients with IIS or TC
      status. It is essential to implement a more homogeneous system for case selection
      through a specific intervention program from the reference center.

PMID- 29579850
TI  - Reasons for Noninclusion on the Kidney Transplant Waiting List: Analysis in a Set
      of Hemodialysis Centers.
AB  - INTRODUCTION: End-stage renal disease patients' access to the renal transplant
      (RT) waiting list (WL) depends on general criteria and their specific application
      in the different treatment units. METHODS: Study in nonhospital hemodialysis
      centers (n = 9), dependent on an adult RT center. Cases included 228 patients
      considered to have nonactive status on the WL due to incomplete immunologic data
      (no blood group or HLA typing) or temporary contraindication from an incomplete
      pretransplant study (nonimmunologic) or comorbidity. Each individual situation
      was studied by reviewing the center's clinical history with the nephrologist in
      charge. RESULTS: Three situations were classified three groups. (1) Patients in
      this group had incomplete basic study (65 patients, 28.5%) pending cardiologic
      evaluation in 34%; urologic evaluation, 26%; both 18%; others, 9%; study not
      initiated, 12%. (2) Patients in this group had pre-existing or onset
      comorbidities (117 patients, 51.3%) pending studies or confirmed resolution:
      obesity, 30%; cancer, 17%; cardiovascular disease, 14%; digestive pathology, 10%;
      infection, 9%; neuropsychiatric disorders, 7%; multiple, 13%. (3) Patients in
      this group had other situations contraindicating RT (46 patients, 20.2%): poor
      therapeutic adherence, 30%; negative will of the patient, 26%; social issues, 9%;
      excluded by the center (not reported), 35%. CONCLUSIONS: We detected a high
      incidence of cases pending basic tests for inclusion on the WL. Obesity can be
      highlighted as the most frequent cause for noninclusion. Further support and
      coordination is required with referral hospital centers to increase and refine
      the RT WL.

PMID- 29579851
TI  - CXCR3+ Monocytes Increase Significantly in Graft Blood Compared to Peripheral
      Blood in Patients With Stable Kidney Graft Function.
AB  - INTRODUCTION: We have recently reported that some lymphocyte populations do not
      maintain the same proportion in kidney graft blood as in peripheral blood,
      despite a stable function of the transplanted kidney. These results suggest that
      a comparative study between leukocyte cells from graft blood and those obtained
      from peripheral blood could provide information about the inflammatory state of
      the transplanted organ. In this work we selected the population of CD4+
      lymphocytes and monocytes expressing CXCR3 to test this hypothesis. MATERIAL AND
      METHODS: The study was performed by flow cytometry during month 3, 6, and 12
      after transplantation in 58 patients who received an isolated kidney transplant
      and the same immunosuppressive regimen. The peripheral blood sample was obtained
      by venipuncture and the graft blood by fine needle aspiration. RESULTS: We found
      a significant percentage decrease in CXCR3+ monocytes throughout the first year
      of transplantation in peripheral blood (15.9 +/- 20.7 vs. 12.6 +/- 12.4 vs. 6.3
      +/- 9.0, at 3, 6, and 12 months, respectively; P = .001), whereas the percentage
      of CXCR3+ monocytes in graft blood did not change over this period. This
      situation resulted in a significant percentage difference between the CXCR3+
      monocytes from the graft blood and those from the peripheral blood at the sixth
      (15.8 +/- 8.1 vs. 12.6 +/- 12.4, respectively; P = .008) and 12th months (12.9 +/
      8.1 vs. 6.3 +/- 9.0, respectively; P < .001). CONCLUSIONS: Therefore, we can
      conclude that the significant percentage increase of CXCR3+ monocytes in graft
      blood with respect to peripheral blood suggests the presence of inflammatory
      activity despite renal function being stable during the second half of the first
      year post-transplantation.

PMID- 29579852
TI  - 24-Hour Proteinuria Versus Spot Protein-Creatinine Ratio for Kidney Transplant
      Management in Clinical Practice.
AB  - BACKGROUND: 24-hour proteinuria (24h-P) has been the most widespread test for
      clinical follow-up of proteinuria after kidney transplantation (KT), but urine
      collection is often not properly collected. Spot protein-creatinine ratio (P/Cr)
      has become the alternative to 24h-P for proteinuria evaluation in many KT units.
      However, its reliability, equivalence to 24h-P, and prognostic value regarding
      allograft outcome remain unknown. Therefore, the aim of this study was to
      evaluate the correlation and agreement between both methods for assessing
      proteinuria and to analyze which of them is a better predictor of graft survival.
      METHODS: We collected proteinuria measurements from KT patients in our center.
      24h-P was adjusted for body surface area. Pearson correlation test and the Bland
      Altman method were used to analyze correlation and agreement. Survival analysis
      was performed with the use of the Kaplan-Meier method and multivariate Cox
      proportional hazard model. RESULTS: A total of 8,549 urine samples were analyzed
      from 472 patients in whom 24h-P and P/Cr were simultaneously measured. A
      significant correlation was observed between 24h-P and P/Cr (r = .76; P < .001);
      however, the agreement between methods showed that P/Cr overestimated proteinuria
      compared with 24h-P, particularly when the latter was >1 g/24 h. The Cox
      regression multivariate model showed an increased risk of graft loss associated
      with proteinuria when assessed by either 24h-P (hazard ratio [HR] 6.53, 95%
      confidence interval [CI] 2.49-17.1) or P/Cr (HR 3.34, 95% CI 1.04-10.7).
      CONCLUSIONS: P/Cr is an method interchangeable with 24h-P for detecting
      proteinuria after KT. When proteinuria increases, the P/Cr overestimates 24h-P,
      even though it also has a significant and similar prognostic value for predicting
      graft survival.

PMID- 29579853
TI  - Survival and Evolution of Renal Function in Kidney Transplant Recipients From
      Type II Asystolic Donations: A Single-center Experience.
AB  - BACKGROUND: In recent years, stagnation in the number of kidneys from after brain
      dead donors (DBD) has stimulated the use of non-heart beating donors (NHBDs).
      Herein we present our 5-year experience with type II Maastricht NHBDs in renal
      transplantation. METHODS: All patients (n = 50) in this study received type II
      Maastricht NHBD kidneys (March 2012 to February 2017), with a median follow-up of
      33 months. RESULTS: Mean donor age was 39 +/- 12 years, mean creatinine 1.24 +/-
      0.2 mg/dL, and the most frequently observed blood group (donors and recipients)
      was type A (64%). Recipients were slightly younger (51 +/- 11 years old), with
      mean time on dialysis of 30 +/- 24 months. Almost all were primary transplants.
      Pre-transplant panel-reactive antibodies (PRA) were <25%; initial
      immunosuppression was thymoglobulin, corticosteroids, mycophenolate mofetil, and
      delayed introduction of tacrolimus. Six percent were nonfunctioning kidneys;
      79.6% presented with delayed renal function (mean duration 14 +/- 9 days). Acute
      rejection was seen in 6% of patients. Mean creatinine at month 3 was 1.7 +/- 0.8
      mg/dL, and 1.5 +/- 0.8 mg/dL in the first year. The last available mean
      creatinine was 1.54 +/- 0.7 mg/dL. Proteinuria in the third month, first year,
      and third year was 0.70, 0.41, and 0.26 g/d, respectively. Recipient survival at
      the first, third, and fifth year was 100%, 100%, and 86%, and when graft-censored
      for death was 94%, 91%, and 91%, respectively. The incidence of acute rejection
      during first year was 6%, and 2% in the second year. Exitus incidence was 4% and
      cytomegalovirus infection was 21.3%. BK viremia between 1000 and 10,000 copies/mL
      was seen in 4.3%, and reached >10,000 copies/mL in 2.1%. CONCLUSIONS: Type II
      NHBD has shown limited frequency of nonfunctioning kidney and high functional
      delay. The results in survival and renal function are very acceptable, comparable
      with levels seen in donation after brain death.

PMID- 29579854
TI  - Influence of Proportion of Normal Saline Administered in the Perioperative Period
      of Renal Transplantation on Kalemia Levels.
AB  - BACKGROUND: The hyperchloremic metabolic acidosis triggered by the infusion of
      normal saline (NS) significantly increases the level of extracellular potassium.
      In this study we assessed the influence of proportion of NS administered in the
      perioperative period of renal transplantation on potassium levels in usual
      clinical practice. METHODS: This study was a retrospective cohort analysis of
      patients undergoing renal transplantation during a 24-month period (2015-2016).
      To determine the influence of NS on K+ levels, simple linear regression and
      multiple linear regression analyses were performed, adjusted for the total volume
      of fluids administered, establishing the difference in serum K+ levels for each
      20% increase in the proportion of NS. RESULTS: As the proportion of NS
      administered increased, K+ levels at 24 hours were significantly increased (P =
      .026) (0.69 mEq/L K+ increase per 20% increase in NS ratio). Mean K+ values at 24
      hours (adjusted for total volume of fluids administered) ranged from 4.17 mEq/L
      (95% confidence interval [CI] 3.7-4.56) in patients who did not receive NS to
      4.85 mEq/L (95% CI 4.56-5.15) in those administered exclusively NS. CONCLUSION:
      The risk of developing hyperkalemia in patients who receive a balanced solution
      with potassium in its formulation compared with NS in the perioperative period of
      renal transplantation is not increased, but the volume of NS administered is
      significantly associated with increases in K+ levels at 24 hours.

PMID- 29579855
TI  - Renal Transplant Immunosuppression in Patients With Hemolytic Uremic Syndrome:
      Four Case Reports.
AB  - A high rate of recurrence has been described in atypical hemolytic uremic
      syndrome renal transplant recipients, favored by certain immunosuppressant drugs
      that can induce complement activation. We present four case series in which three
      patients were diagnosed pretransplantation and a fourth who had onset in the very
      early post-transplantation period. The patients received different
      immunosuppression schedules, and all had improvement after more than 2-years. We
      suggest the need to stratify the risk of atypical hemolytic uremic syndrome
      recurrence using genetic studies and the available drugs as the main factors that
      allow graft survival improvement today.

PMID- 29579856
TI  - Resistant Cytomegalovirus Infection After Renal Transplantation: Literature
      Review.
AB  - BACKGROUND: Resistant cytomegalovirus (R-CMV) is an emerging problem in the renal
      transplantation population. The most frequent CMVs are high-resistance mutations
      (UL97 gene). METHODS: We describe our experience in management of R-CMV after
      renal transplant at our center (2012-2016). RESULTS: We encountered 3 cases of R
      CMV infection after renal transplant (all primary infections). All 3 patients
      received induction therapy with corticosteroids, tacrolimus, and mycophenolate
      mofetil. The first patient (basiliximab induction, preemptive CMV) developed CMV
      replication on day +53, which responded poorly both to standard-dose
      valganciclovir (vGCV) and high-dose ganciclovir (GCV) (creatinine clearance
      [CrCl] >70 mL/min; vGCV 900 mg twice daily for 50 days and GCV 7.5 mg/kg twice
      daily for 8 days). Hematologic toxicity occurred. The R-CMV test was positive and
      foscarnet (FOS) was initiated (90 mg/kg twice daily for 21 days). The second
      patient presented CMV infection (day +30, thymoglobulin induction, CMV
      prophylaxis), which was not controlled with the high dose (CrCl 23 mL/min; GCV
      3.5 mg/kg twice daily and vGCV 900 mg twice daily), resulting in severe
      neutropenia. R-CMV was detected and FOS initiated (FOS 50 mg/kg twice daily for 7
      days and 50 mg/kg every 2 days for 13 days). The third patient's infection
      occurred on day +22 (basiliximab induction, preemptive CMV). Standard-dose vGCV
      was uneffective (CrCl >70 mL/min, vGCV 900 mg twice daily) and it did not respond
      to the high dose (GCV 7.5 mg/kg twice daily and vGCV 2700 mg/d). Moderate
      hematologic toxicity occurred. R-CMV was diagnosed and FOS treatment begun (FOS
      70 mg/kg per day for 2 weeks). CONCLUSIONS: Resistant CMV infection may be severe
      due to viral infection and side effects of high-dose antiviral treatment. We
      presented 3 cases requiring the use of FOS in the absence of response or toxic
      effects from the usual treatment, with an optimal sustained response (temporary
      in case 2) and without serious side effects.

PMID- 29579857
TI  - Cytomegalovirus Infection Monitoring Based on Interferon Gamma Release Assay in
      Kidney Transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common viral infection after kidney
      transplantation and is associated with significant morbidity and mortality.
      Recent studies showed that CMV-specific CD8+ T cells play the crucial role in
      protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN
      gamma) release assay (IGRA test) that measures the IFN-gamma response to a range
      of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility
      of QF-CMV assay to predict CMV infection in kidney transplant recipients and
      evaluated if reactive result in QF-CMV test could be predictor of the duration of
      treatment. METHODS: We studied 75 renal transplant recipients who had IGRA
      testing just before transplantation. The donor and recipient variables were
      reported from the clinical history. The variables related to transplantation were
      collected from transplantation process data and included CMV infection or
      disease, CMV treatment, and immunosuppressive treatment. Laboratory variables
      were C3-C4 complement fractions and DNA quantification of CMV. RESULTS: Fifty
      percent of patients had CMV infection, and 35.9% had CMV disease. The time of
      negativization of CMV DNA was 56.61 +/- 23.5 days. Univariate analysis related to
      CMV infection only showed a statistically significant relation with thymoglobulin
      treatment (P = .001). Statistically significant variables in relation with CMV
      infection incidence were donor serology (P = .044) and thymoglobulin treatment (P
      = .004). The probability of CMV infection was lower with positive IGRA assay (P =
      .025). CONCLUSION: We found that IFN-gamma response measured by QF-MV is a
      protective factor against CMV infection in post-transplantation kidney
      recipients.

PMID- 29579858
TI  - Visceral Leishmaniasis in Renal Transplant Recipients: Report of 2 Cases.
AB  - Visceral leishmaniasis is a disease caused by the protozoan Leishmania and is
      transmitted by Lutzomyia longipalpis (sand fly). It is an endemic parasitic
      infection in numerous areas around the Mediterranean basin. Though
      immunocompetent patients may not develop the disease, in transplant recipients
      the use of corticoids and intensified immunosuppressants to prevent graft
      rejection may accelerate the disease, causing severe damage to the liver, spleen,
      and hematopoietic system. We report 2 cases of visceral leishmaniasis with an
      atypical presentation in transplant recipients. The first patient, who had a
      kidney transplant, was treated successfully with liposomal amphotericin B, and
      the second patient, a combined kidney-pancreas transplant recipient, suffered a
      relapse 3 years after treatment. Visceral leishmaniasis should be considered in
      the differential diagnosis of pancytopenia or unexplained fever occurring after
      organ transplantation in patients living in endemic areas or returning from
      endemic countries.

PMID- 29579859
TI  - Changes in Antihypertensive Therapy After Renal Transplantation.
AB  - INTRODUCTION: Post-transplant hypertension is extremely frequent, occurring in
      60% to 90% of cases. It is involved in the pathogenesis of chronic graft
      dysfunction and patient survival. OBJECTIVES: We sought to describe changes in
      antihypertensive therapy after renal transplantation (RT) depending on the type
      of pretransplant renal replacement therapy (RRT), hemodialysis (HD) or peritoneal
      dialysis (PD). METHODS: We performed a retrospective cohort study of RT patients
      who were divided into 2 groups according to the type of pretransplant RRT (HD
      group: 69 patients; PD group: 38 patients). Patients with a diagnosis of
      nonessential hypertension etiology, diagnosis of renal artery stenosis of the
      graft, active urologic complications, and history of acute graft rejection were
      excluded. Variables related to chronic kidney disease and RT as well as
      antihypertensive therapy were studied. RESULTS: PD patients had reduced number of
      antihypertensive drugs at 1 month after RT (1.39 +/- 1.03) compared with pre-RT
      (2.16 +/- 1.30; P = .001), a trend that was maintained at 6 months (1.70 +/-
      1.18; P = .06). In HD group, the number of antihypertensive drugs increased at 6
      months after RT (1.59 +/- 1.17) compared with pretransplant (1.15 +/- 1.13; P =
      .027). The use of calcium channel blockers increased by 10.2% by 1 month (P =
      .071) and 9.2% (P = .036) by 6 months after RT. CONCLUSION: By 1 month after RT,
      antihypertensive therapy was reduced. Calcium channel blockers were the most
      common drug group, although it is usually necessary to use more than 1 drug.

PMID- 29579860
TI  - Initial Experience in the Use of Novel Auto-expandable Metal Ureteral Stent in
      the Treatment of Ureter Stenosis in Kidney Transplanted Patients.
AB  - INTRODUCTION: Ureter stenosis in renal transplantation patients is a relatively
      frequent complication that negatively conditions graft evolution. The use of
      ureteral stents is a valid treatment alternative to the use of double-J catheters
      in patients for whom surgery is not contemplated or after surgical recurrence. We
      present our initial experience with five patients treated using this technique.
      MATERIALS AND METHODS: We describe a total of five patients with ureteral
      stenosis after renal transplantation who were treated using ureteral stent model
      UVENTA (Taewoong Medical, Seoul, Korea) in our center. The median follow-up was
      18 months (range, 4 to 38 months). We describe the clinical history of patients
      and previous treatments on ureteral stenosis. The technical procedure of
      placement is described. The clinical course is analyzed by measurement of renal
      function and imaging tests, as well as post-stent complications. Survival of the
      renal graft is evaluated. RESULTS: The procedure could be completed in all
      patients without complications. The technique was effective in all patients, with
      correction of creatinine value and hydronephrosis during the renal ultrasound
      test. One patient suffered a urinary tract infection episode associated with the
      use of the ureteral stent. One patient suffered the loss of the renal graft
      secondary to the development of cryoglobulins. One hundred percent of the
      ureteral stents are functioning as of the writing of this article. CONCLUSIONS:
      In renal transplantation patients with ureter stenosis, metallic stents are a
      useful technique with low morbidity and associated complications.

PMID- 29579861
TI  - Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan
      Criteria After Downstaging: Is It Worth It?
AB  - BACKGROUND: The outcome of orthotopic liver transplantation (OLT) for
      hepatocellular carcinoma (HCC) is excellent if it is performed within the Milan
      criteria (ie, single tumor less than 5 cm or 3 tumors less than 3 cm each one and
      no macrovascular invasion). However, after a few studies, it has become possible
      to have a similar survival expanding those criteria. The aim of this study is to
      evaluate the survival of patients with advanced HCC who, after downstaging, did
      not met the Milan criteria although they were within the "up to seven" benchmark,
      and were transplanted at our center in the last 5 years. PATIENTS AND METHODS:
      This is a retrospective study of patients who underwent OLT for HCC in the last 5
      years in our center exceeding Milan criteria despite remaining within the "up to
      seven" benchmark. An observational study of associated factors with overall
      survival based on patient characteristics after OLT was performed. For the
      statistical study, the statistical program SPSS v. 17.0 (Chicago, Illinois,
      United States) was used. RESULTS: We studied 95 patients who had been
      transplanted for HCC in this period, 11 of whom met the study requirements. There
      were 10 (91%) males and 1 female. The mean age of the patients was 54.73 +/- 8.75
      years, with an average waiting list time of 279 days. Nine patients had a Child A
      status, with a mean Model for End-stage Liver Disease score of 9.64 (range, 6 to
      16). The most frequent etiology of cirrhosis was hepatitis C virus infection in 6
      patients (50%) followed by hepatitis B virus infection and ethanolic and
      cryptogenic cirrhosis. Ten patients (91%) had at least one pretransplantation
      transarterial chemoembolization. The survival of patients after 1 year was 75%,
      whereas after 4 years that rate decreases to 25%. At this time, we do not have
      any patients with a 5-year survival rate. The longest survival rate is 55 months.
      CONCLUSIONS: Although the expanded indication of transplantation in HCC raises
      controversies, especially after downstaging, it is possible to provide acceptable
      survival rates for patients within the expanded criteria of "up to seven" after
      locoregional therapies. The performance of a liver transplant in the patient
      profile shown in this article should also be evaluated from the perspective of
      the relative lack of organs for transplantation.

PMID- 29579862
TI  - Liver Transplantation in Recipients With High Model for End-stage Liver Disease
      Score.
AB  - OBJECTIVES: The score in the Model of End-stage Liver Disease, or MELD, is a good
      indicator of the survival in patients on the liver transplant waiting list. In
      this study, an analysis is performed on the benefits of liver transplant on those
      patients with a very high MELD score and who thus start from a very severe
      baseline state that could affect the surgical outcome. MATERIALS AND METHODS: A
      prospective study was conducted on a cohort of 331 patients that received a liver
      transplant between 2002 and 2014. The patients were divided into 2 groups
      according to the MELD score (<28 vs >=28), and differences in age, postoperative
      complications, stay in the intensive care unit (ICU), hospital stay, and survival
      were compared. RESULTS: Of the total of 331 patients, 21 (6.3%) had a MELD score
      >= 28. The mean age of the group with MELD score >= 28 was lower than the age in
      the group with MEDL score < 28 (42.5 vs 53.7 years; P < .0001). No significant
      increase was observed in postoperative complications. Although there were also no
      differences in survival, the group with MELD score >= 28 did have a longer stay
      in ICU and a longer hospital stay (with a mean of 6.7 days in ICU and 41.5 days
      admission vs 4.1 and 26.9, respectively). CONCLUSIONS: A very high MELD score is
      associated with a longer stay in ICU and more days of hospital admission,
      although no differences were observed in postoperative complications or survival.
      Therefore, there does not seem to be any contraindication in transplantation in
      this group of patients.

PMID- 29579863
TI  - Analysis of Indications and Results in Liver Retransplantation: Is Late
      Retransplantation Worthwhile?
AB  - BACKGROUND: Liver retransplantation (LrT) is the only therapeutic option for
      irreversible hepatic graft failure. Despite various improvements, its technical
      complexity entails a greater morbidity in the short and long term. The main goal
      of the study was to analyze the activity of LrT at our center, as well as its
      indications, timing, postoperative evolution, and the long-term survival of
      patients. METHODS: We designed a descriptive study of a cohort of patients who
      underwent LrT in a Spanish Hepatic Transplant Unit, between April 1, 2002 and
      December 31, 2015. RESULTS: A total of 366 primary orthotopic liver
      transplantations were performed, 20 of which were LrTs, resulting in a 5.5%
      retransplantation rate. The most frequent indication for LrT was hepatic artery
      thrombosis (HAT) (35%). Twenty-five percent of the LrTs were early
      retransplantations and 75% were late retransplantations. After LrT, 35% of the
      grafts showed liver dysfunction. The overall mortality rate was 45%: in early LrT
      this was 25% and in late LrT it was 46.7%. Graft actuarial survival at 1 month
      post-LrT was 75% and at 5 years it was 63.6%. The overall actuarial survival
      after LrT at month 1, year 1, year 3, and year 5 was 80%, 69.6%, 58.9%, and
      50.5%, respectively. In the late LrT group, the results proved less favorable, so
      it is necessary to define the minimum acceptable result before proceeding to a
      second graft. CONCLUSION: Our LrT rate was lower than that reported by other
      groups in our country. The actuarial survival rates for graft and patient are
      comparable to those obtained by other groups.

PMID- 29579864
TI  - Outcomes of Liver Transplantation Using Older Donors After Circulatory Death and
      the Super-Rapid Technique: 14 Cases.
AB  - INTRODUCTION: Donation after circulatory death (DCD) has increased in the last
      decade, although a slight increase in surgical complications has been reported in
      liver transplantation (LT). Therefore, DCD is not recommended with donors aged 60
      years or more because it entails an added risk. However, donation after brain
      death (DBD)-LT with donors aged 70 years or more shows acceptable results.
      OBJECTIVE: The objective was to analyze the characteristics and complications of
      DCD-LT with donors aged 70 years or more (DCD-70). MATERIALS AND METHODS: We
      included 14 DCD-70-LT and compared them with a control group of 28 DBD-LT aged 70
      years or more. STATISTICAL ANALYSIS: A descriptive analysis, Mann-Whitney U test,
      and Pearson chi-square or Fisher test were performed when appropriate. RESULTS:
      Significant differences were found in aminotransferase peak at 24 hours, with an
      increase in the DCD-70 group (aspartate aminotransferease [AST] 1038 vs 507, P =
      .013; alanine aminotransferase [ALT] 750 vs 399, P = .014). The cold ischemia
      time was lower in DCD-70 although without significant differences (4.8 vs 6.7
      hours). Biliary complications (28.6% vs 31.7%) and vascular complications (7.1%
      vs 7.1%) were similar. A single transplant with DCD-70 required a
      retransplantation due to arterial thrombosis. Mortality was the same in both
      cases (14.3%). CONCLUSION: LT results with DCD-70 are similar to those of DBD-70,
      so the age criteria could also be extended in this type of donation.

PMID- 29579865
TI  - Analysis of the Predictive Ability for Graft Loss and Mortality of Two Criteria
      for Early Allograft Dysfunction After Liver Transplantation.
AB  - INTRODUCTION: The current imbalance between available donors and potential
      recipients for orthotopic liver transplantation (OLT) has led to a liberalization
      of organ acceptance criteria, increasing the risk of post-transplant
      complications such as early allograft dysfunction (EAD). Consequently, we need
      accurate criteria to detect patients with early poor graft function to guide the
      strategies of management. We evaluated the usefulness of two frequently used
      criteria: the definition from Olthoff et al and the Model for Early Allograft
      Function (MEAF) scoring. PATIENTS AND METHODS: Unicentric cohort study of
      patients undergoing OLT between January 1, 2010, and November 20, 2016. We
      performed a univariate study to detect donor, recipient, and transplant factors
      favoring EAD, defined both by Olthoff criteria and a MEAF score higher than 7.
      Finally, we developed a comparative survival analysis for cases having or not
      EAD. RESULTS: In all, 201 transplants met inclusion criteria. According to the
      stated cutoff for MEAF score, the frequency of EAD was 9.3%, with a significant
      association to low recipient body mass index and prolonged total graft ischemia
      time, resulting in lower patient 3-month postoperative survival. According to
      Olthoff criteria, EAD incidence was 22.1% and was associated with younger donor
      and recipient ages and higher Model for End-stage Liver Disease and Child-Pugh
      recipient scores. Its development resulted in lower graft and recipient survival
      at 3 months after OLT. CONCLUSION: MEAF score and Olthoff criteria are useful
      tools for detection of EAD. The latter could select more appropriately patients
      at risk, but its calculation cannot be done until the seventh day after OLT,
      unlike MEAF score, available on third day.

PMID- 29579866
TI  - How Thinking About the Donor Influences Post-traumatic Growth in Liver Transplant
      Recipients.
AB  - OBJECTIVE: The aim of this work was to find out whether thinking frequently about
      the donor influences post-traumatic growth of liver transplant recipients.
      METHODS: The sample of 240 patients selected was made up of 185 men and 55 women
      with an overall mean age of 60.21 (SD 9.3) years. All of them had received liver
      transplants from cadaver donors. Transplant recipients were asked whether they
      thought frequently about the donor (yes or no) and filled out the Post-traumatic
      Growth Inventory. The t test for unpaired samples was applied to analyze how
      thinking frequently about the donor or not influenced post-traumatic growth. We
      also calculated the effect sizes by means of Cohen d or Cohen w depending on the
      nature of the variables analyzed (quantitative or qualitative). RESULTS: The
      liver transplant recipients who thought frequently about the donor, compared with
      those who did not, had higher total scores on post-traumatic growth (P = .000; d
      = 0.57; medium effect size). Furthermore, considering the effect sizes, the
      differences between the subgroups were more relevant on the following subscales:
      new possibilities (P = .000; d = 0.53; medium effect size), appreciation of life
      (P = .000; d = 0.60; medium effect size), and spiritual change (P = .000; d =
      0.54; medium effect size). CONCLUSIONS: Patients who think frequently about the
      donor have more post-traumatic growth than those who do not.

PMID- 29579867
TI  - Multicentric Study of the Andalusian Experience in Polycystic Liver Disease as
      Indication for Liver Transplantation.
AB  - BACKGROUND: The purpose of this study was to determine the morbidity and survival
      in patients with polycystic liver disease (PLD) undergoing liver transplantation
      (LT) in 4 Spanish hospitals. METHODS: A multicentric retrospective study using a
      prospective database was designed including 19 LTs after PLD diagnosis performed
      from January 1, 1990, to December 31, 2016. Pediatric patients were excluded from
      the analysis. RESULTS: Of the included patients, 63.2% were female, the overall
      average age was 52.16 +/- 11.276 years, median time on the waiting list was 394
      days (interquartile range [IQR], 96.25-464.50) and most of them were classified
      with Model for End-Stage Liver Disease scores of <=17. Eleven patients received
      isolated LT, 1 patient had a previous kidney transplantation (KT), and 7 patients
      received combined liver-kidney transplantation, 4 of them with a previous
      nephrectomy. Complications include hepatopulmonary syndrome in 10.5%, paralytic
      ileus in 10.5%, transient renal dysfunction in 10.5%, and hepatorenal syndrome in
      5.3%. The most common surgical complication was bleeding (15.8%). Three patients
      presented graft rejection, which was treated by means of immunosuppressive
      optimization (15.8%), with corticosteroid addition needed in 1 of them.
      Thrombosis of the hepatic artery occurred in 3 patients, requiring
      retransplantation in 2 of them. Most of the patients had improved renal function
      after the procedure. The mortality rate was 15.8%, related to tumors or sepsis,
      with an estimated 86% 5-year graft survival. CONCLUSIONS: PLD as indication of LT
      presents a low complications rate and better graft survival and renal function,
      especially when KT is associated with LT.

PMID- 29579868
TI  - Results of 15-Year Experience in Liver Transplant for Hepatocellular Carcinoma.
AB  - BACKGROUND: Liver transplant (LT) supposes a curative option for those patients
      with hepatocellular carcinoma (HCC) meeting the Milan criteria. Adjuvant
      therapies, such as transarterial chemoembolization (TACE), can prevent tumor
      progression. Our aim was to analyze the outcomes of patients who have been
      transplanted at our center and to assess the effectiveness of TACE in patients on
      the waiting list for LT. METHODS: Eighty-nine patients who underwent LT for HCC
      at our hospital from 2002 to 2017 were included. Data on the number and size of
      nodules on image testing and explant, frequency of TACE and tumor response,
      mortality, and tumor recurrence were collected. TACE was indicated when waiting
      time was estimated to exceed 6 months in patients with well-preserved liver
      function (Child-Pugh score A-B7). Magnetic resonance imaging (MRI) was performed
      after TACE. RESULTS: We found a single nodule in 64% of patients and multiple
      nodules in 36% of patients. Mean size of nodule on image testing was 38.29 mm,
      similar to the mean size at explant (32.65 mm). TACE was performed in 66 patients
      (74.2%). Ten patients did not meet the Milan criteria at explant, 6 of whom died,
      and 10 patients had tumor recurrence at mean of 22.6 months. Overall mortality
      was 44.9%, but only 10 patients died because of tumor recurrence. CONCLUSIONS:
      TACE responses were achieved in one third of patients and there was an 11.2%
      recurrence rate for HCC. Mortality in our experience has been related to
      exceeding the Milan criteria at explant.

PMID- 29579869
TI  - Efficacy and Safety of Anti-TNF-alpha Agents in Inflammatory Bowel Disease After
      Liver Transplant: A Case Series.
AB  - BACKGROUND: Ulcerative colitis (UC) and Crohn disease (CD) can appear de novo or
      worsen after liver transplant. Our aim was to assess the efficacy and safety of
      anti-tumor necrosis-alpha (anti-TNF-alpha) agents after transplantation. METHODS:
      We reviewed the clinical database of our center searching for all liver
      transplant patients with inflammatory bowel disease who were treated with anti
      TNF-alpha agents between 1997 and 2017. Clinical response was assessed from
      clinical activity indices 12 weeks after starting treatment. The median age of
      the 6 patients (3 women) was 37 years. Four patients were diagnosed before
      transplantation (2 UC and 2 CD), and in the other 2 the disease appeared de novo
      (1 UC and 1 CD). The indications for transplant were primary sclerosing
      cholangitis (n = 3), cryptogenic cirrhosis (n = 2), and hepatitis C virus
      cirrhosis (n = 1). RESULTS: Clinical response was seen in 3 of the 6 patients
      and, in the 3 cases for whom endoscopic data were available, no mucous healing
      was seen. The only adverse effects noted over a mean follow-up of 15 months were
      1 cytomegalovirus infection and 1 severe infusion reaction to infliximab. No
      patients had recurrence of primary sclerosing cholangitis in the graft, and none
      of the patients died. CONCLUSION: Use of an anti-TNF-alpha agent in a liver
      transplant patient with inflammatory bowel disease may be an effective option,
      with an acceptable risk-benefit ratio. Further studies are required to confirm
      their use in this context.

PMID- 29579870
TI  - Matrix Metalloproteinase 1 as a Novel Biomarker for Monitoring Hepatocellular
      Carcinoma in Liver Transplant Patients.
AB  - INTRODUCTION: Orthotopic liver transplantation (LT) is considered to be one of
      the few curative treatments available for early stages of hepatocellular
      carcinoma (HCC). Alfa-fetoprotein (AFP) is the most-used biomarker for HCC
      despite low sensitivity and specificity. Matrix metalloproteinase 1 (MMP-1) has
      been considered to be involved in the process of vascular invasion of the
      malignant cells. The objective of this study was to assess the use of MMP-1 for
      the management of HCC patients for LT. METHODS: Levels in serum of MMP-1 (ng/mL)
      and AFP (ng/mL) were assessed in 20 HCC patients (Milan criteria) before and 1,
      6, and 12 months after LT. RESULTS: There was a strong significant correlation
      between levels of MMP-1 and levels of AFP (rho = .954; P <= .05). There were
      statistical differences in the levels of MMP-1 and APF between the pre
      transplantation and post-transplantation groups (1 and 12 months). Increments of
      both markers 6 months after LT compared with the levels 1 month after LT were
      detected in 4 of the 20 HCC patients. The detection of recurrence by means of
      imaging was coincident with the increment of both markers 6 months after LT in 3
      of those 4 patients. CONCLUSIONS: After 12 months of follow-up, levels of MMP-1
      were comparable to AFP levels after LT. Levels of both markers increase 6 months
      after LT in patients showing recurrence, indicating discriminatory power to
      predict relapse and thus serving as valuable markers for HCC monitoring. MMP-1
      could be useful in the management of HCC after LT.

PMID- 29579871
TI  - Analysis of Ischemic Cholangiopathy After Treatment of Arterial Thrombosis in
      Liver Transplantation in Our Series.
AB  - Liver transplantation offers patients with terminal liver disease an effective
      treatment accompanied by excellent quality of life, but it also has
      complications, such as hepatic artery thrombosis and development of ischemic
      cholangiopathy, described in 3%-17% of patients. It is a very important cause of
      morbidity and mortality. The objective of this report was to analyze the efficacy
      of the treatment they received in relation to the development of ischemic
      cholangiopathy and a comparative survival analysis and to propose prophylactic
      measures for high-risk patients.

PMID- 29579872
TI  - Therapy With Direct-Acting Antiviral Agents for Hepatitis C in Liver Transplant
      Recipients.
AB  - BACKGROUND: Recurrent infection with the hepatitis C virus (HCV) after liver
      transplantation (LT) is associated with decreased graft and patient survival.
      Direct-acting antiviral (DAA) therapies have changed the landscape of HCV due to
      their excellent safety profile and cure rates. Our aim was to evaluate the
      efficacy and tolerability of antiviral therapy in recurrent HCV after LT with DAA
      therapy. METHODS: Our retrospective analysis included 46 LT recipients with HCV
      recurrence. Patients received therapy with DAA therapy between November 2014 and
      May 2016. Stage of fibrosis was documented by transient elastography (FibroScan).
      RESULTS: Thirty-three of the patients were men (71.7%), with a mean age of 59.6
      years. Most patients were infected with HCV genotype 1 (71.7%) (1a = 7, 1b = 26)
      or genotype 3 (19.6%). Cirrhosis was present in 10 (21.7%). The most frequent
      immunosuppression regimen was tacrolimus + mycophenolate mofetil (MMF) (41.3%).
      Most patients received sofosbuvir + simeprevir (SOF+SMV) (n = 13, 28.3%) and
      sofosbuvir + daclatasvir (SOF+DCV) (n = 15, 32.6%). A virologic response at
      posttreatment week 12 was detected in 93.8% of the patients. Two patients failed
      treatment (1 had resistance-associated variants [RAVs] Y93H in NS5A). Three
      patients died due to chronic rejection, acute arterial thrombosis, and
      spontaneous bacterial peritonitis. Adverse events were observed in 23 patients
      (50%). The most common events were asthenia in 17 (37%) and headache in 6 (13%)
      patients. One patient discontinued treatment due to serious adverse events
      attributable to the drug's interaction with tacrolimus. CONCLUSIONS: DAAs are
      safe and effective for use in treating HCV recurrence after LT, with results
      similar to those seen in the general population, including patients with
      cirrhosis.

PMID- 29579873
TI  - Long-term Survival and Evolution of the Kidney Function for Liver Transplant
      Patients Who Required Postoperative Dialysis.
AB  - Patients who underwent orthotopic liver transplantation (OLT) frequently develop
      chronic kidney disease, with those who present postoperative acute kidney failure
      and require renal replacement therapy (RRT) at higher risk. The objective of the
      study was to assess the kidney function and long-term survival of patients who
      underwent OLT and required RRT during or in the immediate postoperative period.
      Medical records of OLT and postoperative RRT patients with over 6-month survival
      were reviewed between January 1, 2005, and December 31, 2015. A variance analysis
      was carried out for repeated measurements to compare the estimate glomerular
      filtration rate (eGFR) baseline with the different periods (statistical
      significance level P < .05). Kaplan-Meier estimator was used to estimate the
      survival rate. Of 539 patients, 20 (3.7%) met the selection criteria. The basal
      eGFR at 6 months and 1, 3, 5, and 7 years was 93.41 +/- 25, 78.28 +/- 33, 73.06
      +/- 29, 65.96 +/- 19, 79.81 +/- 28, and 59.06 +/- 24 mL/min/1.73 m2,
      respectively. The comparison of the eGFR baseline within the different periods
      was statistically significant at 1 year and at 3 years. Four patients died, 3 of
      them due to sepsis and 1 due to recurrence of hepatitis C virus infection. The
      average survival was 28 months. The probability of surviving at 1 year was 100%,
      at 3 years was 84.21% (95% confidence interval: 58.65-94.62), and at 5 and 10
      years was 78.6% (95% confidence interval: 52.49-91.39). In conclusion, we have
      found a progressive worsening of the kidney function in the long term in patients
      who required postoperative dialysis. However, actuarial survival of these
      patients was very successful.

PMID- 29579874
TI  - Cold Ischemia Time as a Factor in Post-transplantation Complications for
      Orthotopic Hepatic Transplantation.
AB  - OBJECTIVE: This study aims to compare a shorter cold ischemia time with the
      present one in relation to the complications developed in liver transplantations.
      DESIGN: This is a retrospective, observational study of orthotopic liver
      transplantations performed with grafts from brain-dead donors during 12 months at
      a University Hospital (Seville). We compare incidence rates of complications
      (reperfusion syndrome, arterial and biliary complications, and prostaglandin
      requirements) between two groups according to cold ischemia times (group A < 6
      hours; group B > 6 hours). RESULTS: Sixty cases were included. There were more
      males in both groups as donors (55.5%) and recipients (75%). The median age was
      higher in group B in two cases. The Model for End-stage Liver Disease score was
      higher in patients with a shorter cold ischemia time, with a median of 20 hours
      (range, 16 to 26.5 hours). We observed that reperfusion syndrome (3.4% vs. 13.3%;
      P = .353), vascular complications (6.9% vs. 24.1%; P = .144), biliary tract
      complications (13.8% vs. 20.7%; P = .730), and prostaglandin requirements (3.4%
      vs. 20.7%; P = .102) were more common in group B, although without reaching
      statistical significance. After uni- and multivariate analyses, cold ischemia
      time longer than 6 hours was the only risk factor to develop complications (odds
      ratio: 3.578; 95% confidence interval: 1.125 to 11.374, P = .031). CONCLUSION:
      According to the results of our analysis, cold ischemia times longer than 6
      hours, as tends to be the usual procedure in most centers, imply higher rates of
      complications after liver transplantation.

PMID- 29579875
TI  - Donors Older Than 75 Years Do Not Influence the Appearance of Biliary
      Complications After Liver Transplantation.
AB  - BACKGROUND: In recent years, several studies have shown that the age of the donor
      may be related to an increase in the occurrence of biliary complications (BCs),
      which remain the main cause of morbidity after liver transplantation. This study
      analyzed the type and management of these BCs, the impact of BCs on graft and
      patient survival rates, and the influence of some characteristics of donors and
      recipients on BC appearance in patients transplanted with donors 75 years of age
      or older. PATIENTS AND METHODS: From 2003 to 2016, 100 liver transplantations
      with donors 75 years of age or older (15.6%) were performed in our hospital. The
      data were compared with a control group of 400 patients with younger donors (case
      control 1:4 per chronology). RESULTS: The BC rate in the group of patients
      transplanted with organs from elderly donors was 18%, compared to 21.5% in the
      control group. Specifically, in the immediate post-transplantation period, 14% of
      the elderly donor group and 13.8% of the control group presented some BCs, with
      no statistically significant differences in the incidence, type, and treatment of
      BCs between the two groups. The occurrence of BCs was not a factor associated
      with graft and patient survival rates. In the global population, donor death by
      cerebral vascular accident and male donors have influenced the occurrence of BCs.
      CONCLUSIONS: The advanced age of the donor has not influenced BC rates after
      transplantation.

PMID- 29579876
TI  - Orthotopic Liver Transplantation: Preliminary Analysis of Complications With
      Grafts From Elderly Donors.
AB  - OBJECTIVE: This study aims to determine if donor grafts of patients older than 65
      years develop more post-transplantation complications than those of younger
      patients. DESIGN: This is a retrospective, observational study of liver
      transplant recipients during 12 months in Virgen del Rocio University Hospital.
      We compare incidence rates of reperfusion syndrome, acute kidney injury, and need
      for intra- and postoperative red blood cell transfusions in two donor age groups
      in which group A is <65 years old and group B is >=65 years old. RESULTS: Sixty
      cases were included. Reperfusion syndrome, acute kidney injury, and both intra-
      and postoperative red blood cell transfusion were more frequent in group A than
      group B (11.4% vs. 4%, P = .390; 44% vs. 32%, P = .423; 68.8% vs. 48%, P = .120;
      and 70.6% vs. 64%, P = .779, respectively). Six recipients (17.1%) died at 12
      months from group A whereas there were no deaths register in group B during that
      time (P = .036). CONCLUSION: Our results showed that including elderly donors
      does not aggravate incidence of complications, emphasizing that advanced age
      should not be an exclusion criteria for liver transplantation.

PMID- 29579877
TI  - Family Caregivers of Liver Transplant Recipients: Coping Strategies Associated
      With Different Levels of Post-traumatic Growth.
AB  - OBJECTIVE: Analyze the influence of 2 variables (post-traumatic growth and time
      since liver transplantation) on coping strategies used by the transplant
      recipient's family members. METHODS: In all, 218 family members who were their
      main caregivers of liver transplant recipients were selected. They were evaluated
      using the Posttraumatic Growth Inventory and the Brief COPE. A 3 * 3 factorial
      analysis of variance was used to analyze the influence that post-traumatic growth
      level (low, medium, and high) and time since transplantation (<=3.5 years, >3.5
      to <=9 years, and >9 years) exerted on caregiver coping strategies. RESULTS: No
      interactive effects between the two factors in the study were found. The only
      significant main effect was the influence of the post-traumatic growth factor on
      the following variables: instrumental support (P = .007), emotional support (P =
      .005), self-distraction (P = .006), positive reframing (P = .000), acceptance (P
      = .013), and religion (P = <.001). According to the most relevant effect sizes,
      low post-traumatic growth compared with medium growth was associated with less
      use of self-distraction (P = .006, d = -0.52, medium effect size), positive
      reframing (P = .001, d = -0.62, medium effect size), and religion (P = .000, d = 
      0.66, medium effect size), and in comparison with high growth, it was associated
      with less use of positive reframing (P = .002, d = -0.56, medium effect size) and
      religion (P = .000, d = 0.87, large effect size). CONCLUSION: Regardless of the
      time elapsed since the stressful life event (liver transplantation), family
      members with low post-traumatic growth usually use fewer coping strategies
      involving a positive, transcendent vision to deal with transplantation.

PMID- 29579878
TI  - Prognostic Value of Blood Panel Parameters in Patients With Dilated
      Cardiomyopathy and Advanced Heart Failure.
AB  - BACKGROUND: Patients with dilated cardiomyopathy (DCM) and left ventricular
      dysfunction have a varied clinical course, not only dependent on left ventricular
      ejection fraction (LVEF) and symptoms. Finding prognostic markers for
      stratification in these 2 conditions is a critical area of research. Our aim was
      determine the prognostic value of blood panel basic parameters. METHODS: We
      analyzed all patients with idiopathic or familial DCM and LVEF <30% coming to our
      heart failure unit for evaluation for non-urgent heart transplant during the
      period of 2009 to 2011. With 5 years of follow-up data, we could study the
      prognostic value of blood panel parameters. Moreover, we determined the
      combination of platelet count and neutrophil to lymphocyte ratio score from the
      BIOSTAT-CHF study. RESULTS: Eighty-seven patients were included in the study.
      After 5 years follow-up, 49 patients (57%) remain alive (group A) and 38 (43%)
      either died or needed a heart transplant. There were no differences between
      groups with regard to age or sex. Patients with good progress showed a lower red
      cell distribution width (RDW), a higher lymphocyte count, and a lower
      neutrophil/lymphocyte ratio in the initial blood panel. An RDW >=15% was
      associated with long-term mortality or heart transplant. CONCLUSION: A basic
      blood panel could be a useful tool in assessing patients with heart failure.
      Larger studies are necessary to confirm our findings. A multimarker strategy
      could also be useful for stratification of patients with advanced heart failure.

PMID- 29579879
TI  - Short-term Use of Ventricular Assist Device in a Patient With Restrictive
      Cardiomyopathy: A Case Report.
AB  - The CentriMag (Levitronix LLC, Waltham, MA, USA) ventricular assist device is a
      centrifugal pump designed for short-term support in patients with cardiogenic
      shock. In patients with restrictive physiology, there is some concern about the
      use of these devices due a very small ventricular cavity. We review the evolution
      of a 32-year-old woman with restrictive cardiomyopathy, moderate pulmonary
      hypertension, and severe biventricular systo-diastolic dysfunction in whom a
      biventricular Centrimag device was implanted due to a progressive clinical
      worsening.

PMID- 29579880
TI  - Complex Congenital Heart Disease: Is Heart Transplantation an Option?
AB  - INTRODUCTION: Within the heart transplant (HT) population, few patients have
      complex congenital heart disease (CHD) underlying disease. Our objective is to
      assess the complications and follow-up of patients with CHD transplanted in our
      center (1991-present). MATERIAL AND METHODS: Retrospective analysis of patients
      older than 14 years old with CHD and HT. Clinical and surgical variables were
      analyzed. RESULTS: Ten patients (age 25 +/- 7 years old, 60% male) were analyzed,
      which represents 2.2% of the entire series of HT; 9 of the 10 patients were
      electively transplanted and 1 was under support with extracorporeal membrane
      oxygenation. Compared with the rest of the transplanted patients, patients with
      CHD had a lower median age (25 [25-36] vs 53 [15-69]; P < .009); more cardiac
      surgeries prior to HT (100% vs 14.4%; P < .001); a lower percentage of
      cardiovascular risk factors (CVRF; 0% vs 60%; P < .001). The left ventricle
      ejection fraction also showed statistically significant differences (33.5 [12-67]
      vs 20 [6-70]). CONCLUSIONS: Our patients with CHD and HT are younger and have
      less CVRF and more cardiac surgeries, which highlights that it is a subgroup with
      clear clinical differences in its comorbidity and pretransplantation assessment.
      They also require longer extracorporeal circulation time, more hours of
      intubation, and more days in the intensive care unit. Primary graft failure is
      more common in patients with CHD. Therefore, survival at 1-month follow-up is
      lower than the rest of the series and equalizes after the year of follow-up. This
      long-term survival reaffirms the possibility of HT in CHD despite the fact that
      its postoperative period is more difficult.

PMID- 29579881
TI  - Long-term Prognosis After Lung Transplantation: A Monocentric Study in 510
      Patients.
AB  - INTRODUCTION: Lung transplantation is the final treatment option in patients with
      respiratory failure. Morbidity and mortality rates associated with the management
      of complications is high despite advances. Postoperative complications include
      acute transplant rejection, bronchiolitis obliterans, and infections. Because of
      that, the success of this treatment option depends on the correct choice of donor
      and candidates to receive a transplant. OBJECTIVE: This study aims to perform a
      survival analysis of transplanted patients in our center and determine predictive
      variables of mortality. PATIENTS AND METHODS: This study is a retrospective
      assessment of data collected from 510 patients at the Hospital University Reina
      Sofia from October 1993 to December 31, 2016. Patients who were retransplanted
      were excluded. We collected data regarding basal characteristics of the donors
      and candidates to receive a transplant. We analyzed the impact in terms of future
      survival of basal variables from donor and donor recipients. RESULTS: Five
      hundred ten patients were included (average age 44 +/- 17 years, 69% male), with
      a maximum follow-up period of 21.6 years (average follow-up 4.52 years,
      interquartile ratio: 0.13 to 6.97 years). Two hundred twenty-seven patients died
      (54.3% of the total amount). The influence of donor's basal characteristics on
      mortality was analyzed; moreover, the relationship between basal variables and
      survival were analyzed using univariate analysis. Available variables were
      analyzed through multivariate analysis. CONCLUSION: Lung transplantation is a
      treatment option with an acceptable risk of morbidity and mortality. Increased
      awareness of features of evolution could help to reduce postoperative
      complications.

PMID- 29579882
TI  - Left Single Lung Transplantation Through Left Anterolateral Thoracotomy With
      Longitudinal Partial Sternotomy (Hemiclamshell): An Innovative Surgical Resource.
AB  - INTRODUCTION: Pulmonary fibrosis (PF) is one of the main indications for lung
      transplantation among end-stage respiratory diseases. PF represents a surgical
      challenge due to the pulmonary retraction, reduction of pleural space, and
      limitation for access of the lung hilum by elevation, specifically on the left
      lung. Unilateral sternothoracotomy, or hemiclamshell (HCS) approach, is the
      anterolateral thoracotomy with longitudinal partial sternotomy with possibility
      of cervical extension. This was initially described as a surgical approach for
      resection of lung apex tumors and of the cervicothoracic region, excision of
      mediastinal and thoracic wall tumors, and as an urgent incision for the repair of
      mediastinal and cervicothoracic vascular lesions. HCS is not usually described
      for liver transplantation. CASE: A 62-year-old man who was a nonsmoker was
      diagnosed with idiopathic PF. After 3 years of medical management and follow-up,
      the patient was referred to us for a pretransplantation study. He presented with
      dyspnea grade III according to the Medical Research Council. In the radiograph of
      the chest and computed tomography of the thorax showed signs of pulmonary
      fibrosis predominantly left-lung associated with loss of volume and alteration of
      respiratory function tests. We performed left single lung transplantation through
      a left HCS approach. During implantation we converted the superior pulmonary vein
      into "neo-atrium" for the atrial anastomosis. The patient presented excellent
      evolution and was discharged from the hospital at 26 days. CONCLUSION: We present
      a case of left single lung transplantation by PF through an HCS approach as novel
      and effective resource for this type of procedure.

PMID- 29579883
TI  - What Is the Influence of Both Risk Donor and Risk Receiver on Simultaneous
      Pancreas-Kidney Transplantation?
AB  - INTRODUCTION: Some factors affect the pancreas of a marginal donor, and although
      their influence on graft survival has been determined, there is an increasing
      consensus to accept marginal organs in a controlled manner to increase the pool
      of organs. Certain factors related to the recipient have also been proposed as
      having negative influence on graft prognosis. The objective of this study was to
      analyze the influence of these factors on the results of our simultaneous
      pancreas-kidney (SPK) transplantation series. MATERIALS AND METHODS:
      Retrospective analysis of 126 SPK transplants. Donors and recipients were
      stratified in an optimal group (<2 expanded donor criteria) and a risk group (>=2
      criteria). A pancreatic graft survival analysis was performed using a Kaplan
      Meier test and log-rank test. Prognostic variables on graft survival were studied
      by Cox regression. Postoperative complications (graded by Clavien classification)
      were compared by chi2 test or Fisher test. RESULTS: Median survival of pancreas
      was 66 months, with no significant difference between groups (P > .05).
      Multivariate analysis showed risk factors to be donor age, cold ischemia time,
      donor body mass index, receipt body mass index, and receipt panel-reactive
      antibody. CONCLUSIONS: In our series, the use of pancreatic grafts from donors
      with expanded criteria is safe and has increased the pool of grafts. Different
      variables, both donor and recipient, influence the survival of the pancreatic
      graft and should be taken into account in organ distribution systems.

PMID- 29579884
TI  - Prevalence and Survival of Cancer After Pancreas-Kidney Transplantation.
AB  - BACKGROUND: Malignancy is an important cause of mortality in solid organ
      transplantation. There have been few studies of de novo solid organ malignancy
      (NSOM) after pancreas-kidney transplantation (PKT). The aim of this study was
      analyze the prevalence of NSOM and transplant outcomes. METHODS: We studied the
      development of NSOM after PKT in our center from May 1990 to February 2017. We
      analyzed demographic characteristics, prevalence of cancer, and survival after
      cancer diagnosis. We excluded nonmelanoma skin cancer and patients with history
      of malignancy before transplantation. RESULTS: We included 194 patients who
      received 206 PKTs (184 simultaneous PKTs and 22 pancreas after kidney
      transplants) with triple immunosuppressive therapy and basiliximab in more than
      95%. The mean age at transplantation was 39 +/- 7 years and 74% were male
      patients. Twelve patients developed malignancies (6.1%). Median time from
      transplant to NSOM was 6.6 (interquartile range [IQR] 0.2-11.7) years. The
      malignancies were 2 cecal appendix tumors, 2 hematologic tumors, 2 breast tumors,
      1 melanoma, 1 native kidney tumor, 1 brain tumor, 1 bladder tumor, 1 prostate
      tumor, and 1 leiomyosarcoma. Thirty-five of the 194 patients of the whole cohort
      died throughout the follow-up, 4 of whom died after NSOM diagnosis (11.4%).
      Patient and grafts survivals were lower in recipients with tumor compared with
      recipients without tumor, but the difference was not statistically significant:
      renal graft survival was 80% vs 90% at 10 years (P = .86); and pancreatic graft
      survival was 45% vs 70% at 10 years (P = .15), respectively. The mean patient
      survival time from the diagnosis of cancer was 36.6 (IQR 18-54) months. Patient
      survival after NSOM diagnosis was 90% at 1 year and 50% at 5 years. CONCLUSION:
      The prevalence of NSOM in our PKT recipients is low, despite the scarce series of
      published data for comparison. Also hematologic tumors rate is very low, possibly
      influenced by age and type of induction.

PMID- 29579885
TI  - Intraoperative Heparinization During Simultaneous Pancreas-Kidney
      Transplantation: Is It Really Necessary?
AB  - INTRODUCTION: The use of intraoperative sodium heparin during simultaneous
      pancreas-kidney transplantation (SPKT) remains as a routine practice in some
      referral centers to minimize pancreatic graft thrombosis rate. One of its
      disadvantages is the theoretical increased risk of postoperative bleeding. In our
      center, we have abandoned its use since 2011. MATERIALS AND METHODS: We performed
      a retrospective analysis among 198 SPKTs performed in our center between the
      years 1989 and 2017. The variables of our study were vascular thrombosis of the
      pancreatic graft and hemoperitoneum and upper gastrointestinal bleeding in the
      mediate postoperative period (up to 2 months after the transplant). We compared
      these results between SPKT recipients who had undergone intraoperative
      heparinization (n = 157) and those who had not (n = 51). To avoid bias, a second
      comparison was performed using propensity score matching on the following
      characteristics: sex, recipient age, recipient body mass index, cold ischemia
      time, preoperative hemodialysis or peritoneal dialysis, time of diabetes, and
      Pancreas Donor Risk Index. Student t test or Mann-Whitney U test was used for
      intergroup comparisons of quantitative variables where appropriate, whereas chi2
      or Fisher exact test was used to compare categorical data. RESULTS: No
      statistically significant differences were found when comparing the use of
      intraoperative heparin, even after the homogenization of both groups.
      CONCLUSIONS: In our experience, intraoperative heparinization during SPKT surgery
      was not useful because it did not significantly decrease the graft thrombosis
      rate, and its withdrawal did not enhance hemoperitoneum or upper gastrointestinal
      bleeding postoperative rates.

PMID- 29579886
TI  - Pancreas Donor Hypernatremia: Is it Really a Risk Factor for Simultaneous
      Pancreas-kidney Transplantation?
AB  - INTRODUCTION: Solid organ donor hypernatremia has been classically reported to be
      a risk factor for cell lysis and graft damage. National criteria for pancreatic
      donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be
      relative exclusion criteria. The aim of our study is to review the postoperative
      outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in
      terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas
      graft thrombosis, early pancreatectomy, and reoperation rates regarding different
      ranges of donor sodium levels. MATERIAL AND METHODS: We performed a retrospective
      analysis among 161 SPKTs performed in our center between the years 2001 and 2017.
      We compared the aforementioned postoperative variables in two situations: 1)
      Whether the donor pancreas sodium levels were inferior to 149 mEq/L, or equal to
      or greater than 150 mEq/L; and 2) If they had severe hypernatremia (considering
      sodium levels greater than or equal to 160 mEq/L as threshold) or not. To ensure
      the comparability of the groups, a second comparison was performed on new samples
      after using propensity score matching. A Student t test or Mann-Whitney U test
      was used for intergroup comparisons of quantitative variables where appropriate,
      whereas a chi2 test or Fisher's exact test was used to compare categorical data.
      RESULTS: No statistically significant differences were found between the groups
      that relate high donor serum sodium levels with the morbidity variables included
      in our study or with early pancreatic graft loss. CONCLUSIONS: In our cohort,
      early postoperative main morbidity and pancreas graft loss of SPKT recipients do
      not differ significantly regarding donor serum sodium levels.

PMID- 29579887
TI  - Donor Selection Based on Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype
      May Improve Outcome After T-Cell-Replete Haploidentical Transplantation.
AB  - BACKGROUND: In haploidentical stem cell transplantation (SCT), the "ideal donor"
      selection is not performed in a standardized way according to killer cell
      immunoglobulin-like receptor (KIR) genotype expressed by potential donors. The
      aim of this study was to evaluate the relevance of KIR genotype in a series of
      patients submitted to haploidentical SCT in our center. METHODS: We
      retrospectively analyzed 30 patients that were prepared with the use of a
      conditioning regimen including thiotepa-busulfan-fludarabine with high doses of
      post-transplantation cyclophosphamide (CyPT) and tacrolimus as graft-versus-host
      disease (GVHD) prophylaxis. We analyzed the impact of the KIR genotype variables
      (donor AA/Bx haplotype, donor B content, KIR inhibitor mismatches, and
      mismatching in KIR ligands in the graft-versus-host direction and the host-versus
      graft direction) on overall survival, GVHD-free survival, and event-free
      survival. RESULTS: Statistical significance was found for the presence of
      mismatches on KIR ligands in the graft-versus-host direction in relation to the
      diagnosis of chronic GVHD (54% vs 100%; P = .004). Significance was also found
      for the effect of the donor presence AA or Bx haplotype in relation to the
      diagnosis of chronic GVHD (50% vs 86%; P = .033). CONCLUSIONS: KIR genotyping can
      provide useful information that can help us with the right donor choice for
      haploidentical SCT without T-cell depletion with high doses of CyPT. Donors with
      Bx haplotype that do not show KIR ligand incompatibilities in the graft-versus
      host direction may provide a lower risk of GVHD.

PMID- 29579888
TI  - Severe Scedosporium apiospermum Infection in a Recent Renal Transplant Recipient:
      Case Report.
AB  - Infections in transplanted patients are still an important cause of morbidity and
      mortality. Among them, fungal infections with pathogens have become increasingly
      more prevalent in the last decade. We report the clinical course and management
      of disseminated Scedosporium apiospermum infection in a kidney transplant
      recipient, with microbiological isolation of the fungus in cerebrospinal fluid
      culture. S apiospermum is a fungus that is distributed worldwide and can be grown
      from soil samples or stagnant water. Disseminated infection is the most frequent
      form of infection, with cerebral involvement in most cases, which leads to a very
      high mortality (around 75%). Post-transplant renal infections require a thorough
      evaluation. Specifically, a high suspicion index is necessary, considering
      Scedosporium infection among the differential diagnosis of invasive fungal
      diseases in renal transplantation patients. It is essential to confirm the
      microbiological diagnosis for an adequate diagnosis and treatment.

PMID- 29579889
TI  - Retransplant Due to Fulminant Hepatic Failure From Hepatitis E Virus: A Case
      Report.
AB  - Hepatitis E virus (HEV) usually causes self-limiting acute liver infections from
      fecal or oral transmission, though other routes of infection exist (vertical
      transmission, blood transfusion, zoonosis). It may give rise to fulminant hepatic
      failure in 1% of cases. Cases have recently been reported of chronic infection
      evolving to cirrhosis in immunosuppressed patients, such as those with a liver or
      kidney transplant. Nonetheless, development of acute liver failure in these
      patients is exceptional, with few cases published. We present a case of acute
      liver failure due to HEV in a liver transplant patient who required a liver
      retransplant 9 years after receiving the original transplant.

PMID- 29579891
TI  - Erratum.

PMID- 29579890
TI  - Molecular Adsorbent Recirculating System Treatment Can Reduce Blood Levels of N
      Acetylcysteine in Patients With Acetaminophen Overdose: Case Reports.
AB  - BACKGROUND: Acetaminophen poisoning continues to be a major cause of liver
      failure that can lead to liver transplantation. N-acetylcysteine (NAC) is the
      cornerstone of treatment. Some authors use a Molecular Adsorbent Recirculating
      System (MARS) system in acetaminophen poisoning. It is reported that the MARS
      system eliminates acetaminophen more efficiently than conventional dialysis. It
      is theoretically possible that treatment with MARS administered after NAC will
      increase the effectiveness of treatment. CASE REPORTS: The first patient, a woman
      of 14 years old, presented blood levels of 112 mg/dL 12 hours after ingestion of
      15 g of acetaminophen. Treatment with NAC was initiated. At 17 and 23 hours after
      ingestion, blood levels were 23.5 MUg/mL and 5.9 MUg/mL, respectively. The second
      patient, a woman of 28 years old, presented blood levels of 115 mg/dL 4 hours
      after ingestion of 40 g of acetaminophen. Treatment with NAC was initiated. At 14
      and 23 hours after ingestion, blood levels were 15.8 MUg/mL and <2 MUg/mL,
      respectively. In both patients, we performed MARS after completing treatment with
      NAC, and after the first session, blood levels were below the lower limit of
      detection (<=2 MUg/mL). DISCUSSION: The correct timing of MARS to avoid
      interactions with the administered dose of NAC in acetaminophen overdose is
      essential so as to not impair the effectiveness of this treatment. These
      considerations in the management of this entity help in the resolution of liver
      failure, thus avoiding the need for a liver transplant.

PMID- 29579892
TI  - Tds of cheese: Implications of analyzing texture and taste simultaneously.
AB  - This study aimed to evaluate the implications of analyzing texture and taste
      simultaneously on Temporal Dominance of Sensations (TDS) descriptions of Prato
      cheese. TDS tests were performed in two ways: I-panelists performed TDS tests of
      cheeses evaluating an attribute list with taste and texture sensations in a same
      session; II-TDS sessions were performed for each sensory modality. The difficulty
      and reliability degrees on performing the tests were assessed by the panelists;
      and some physico-chemical parameters were determined to compare the sensory and
      instrumental results. During TDS tests, simultaneous evaluations provided a
      higher number of significant sensations (considering both taste and texture
      sensations), but at lower dominance rates. Moreover, it was noted that one of the
      main implications of the simultaneous analysis on TDS results was the temporality
      differences (the time to reach the significance level, the sensation duration and
      the sensations sequence). However, regarding only the attributes that most
      characterized the samples, the results suggested a great similarity between the
      descriptions obtained from both TDS modalities. The simultaneous analysis implied
      greater difficulty in performing the tests and less reliable results according to
      the panelist's opinions. Moreover, the panel considered the texture evaluation
      more difficult than the taste evaluation. Regarding the instrumental analysis,
      the physico-chemical parameter intensity (amplitude) was not strongly linked to
      the maximum dominance rate.

PMID- 29579893
TI  - Environmental impacts of chocolate production and consumption in the UK.
AB  - This study evaluates life cycle environmental impacts associated with chocolate
      products made and consumed in the UK. The paper focuses on three representative
      chocolate products occupying 90% of the market: 'moulded chocolate', 'chocolate
      countlines' and 'chocolates in bag'. The impacts were estimated using life cycle
      assessment (LCA) as a tool and following the ReCiPe impact assessment method. The
      water footprint was also considered. For example, the global warming potential
      ranges between 2.91 and 4.15 kg CO2 eq., primary energy demand from 30 to 41 MJ
      and the water footprint, including water stress, from 31 to 63 l per kilogram of
      chocolate. The raw materials are the major hotspot across all impact categories
      for all three product types, followed by the chocolate production process and
      packaging. The raw material impacts are mainly due to milk powder, cocoa
      derivatives, sugar and palm oil. The sensitivity analysis shows that the results
      for global warming potential are sensitive to land-use change (LUC) associated
      with cocoa production, increasing the impact of the chocolate products by three
      to four times if LUC is involved. The improvement opportunities targeting the key
      contributing stages suggest that GWP of chocolates could be reduced by 14%-19%.
      Chocolate countlines have the highest contribution to the total impacts at the UK
      level (37%-43%), followed by chocolates in bag (28%-33%). Moulded chocolates and
      other chocolate confectionary make up the rest of the impacts, with a roughly
      equal share each. Chocolate consumption in the UK contributes 4.7% to the primary
      energy consumption and 2.4% to the GHG emissions from the whole food and drink
      sector. The results of this work will be of interest to policy makers, chocolate
      producers and consumers, helping them to make more informed decisions towards
      sustainable production and consumption of chocolate products.

PMID- 29579894
TI  - Synergistic effects of nutmeg and citrus peel extracts in imparting oxidative
      stability in meat balls.
AB  - Nutmeg (NM) and citrus peel (CP) extracts are potential sources of phytochemicals
      high in antioxidant activity. The synergistic effect of the extracts when
      incorporated as a binary mixture (NM-CP) demonstrated high antioxidant activity,
      exceeding the expected values indicating possible interactive synergism. This
      effect prompted us to investigate the potential of NM, CP and NM-CP extracts in
      imparting oxidative stability to meat balls during frozen storage. NM-CP was
      evaluated at two concentrations 0.5% (NMCP) and 1.0% (NMCP1). Meat balls with
      added salt (MS) and control (without any salt and antioxidant) served as control.
      Binary mixture (NM-CP) at 1% showed a stronger inhibitory effect on lipid
      oxidation in comparison to the NMCP and individual extracts NM and CP. However,
      with respect to protein oxidation, both concentrations (NMCP and NMCP1) exhibited
      higher inhibitory activity than the individual counterparts. Color, flavor and
      sensory scores further confirmed the efficacy of NM-CP in extending the storage
      life of frozen meat. Synergistic effect of binary extract NMCP in retarding lipid
      and protein oxidation in meat balls could be of practical value for meat
      processors.

PMID- 29579895
TI  - Evaluating the efficacy of turbimetric measurements as a rapid screening
      technique to assess fungal susceptibility to antimicrobial compounds as
      exemplified by the use of sodium metabisulfite.
AB  - The in vitro susceptibility to sodium metabisulphite (NaMBS) was investigated in
      10 different food spoilage filamentous fungi, namely Aspergillus flavus, A.
      carbonarius, A. niger, A. ochraceus, A. tubingensis, A. westerdijkiae,
      Cladosporium cladosporioides, Fusarium oxysporum, Penicillium commune and P.
      expansum. The fungi were inoculated in sterile 96-well microtiter plates
      containing Yeast-extract Sucrose (YES) semi-solid agar supplemented with NaMBS in
      concentrations ranging from 2000 to 3.9 mg l-1 and incubated at 25  degrees C.
      Growth was monitored by absorbance measurements at 600 nm using a multi
      spectrophotometer. The surface areas under the optical density (OD) vs. time
      growth curves obtained were used to calculate the fractional area f(a), from
      which the non-inhibitory (NIC) and minimum inhibitory concentrations (MIC) of the
      antifungal agent were calculated for each fungus using the Gompertz model for
      decay. Most Aspergillus species showed remarkable resistance to NaMBS, presenting
      NIC and MIC values higher than 250 and 2500 mg l-1, respectively. The most
      susceptible fungi were the two Penicillium species and A. carbonarius, which
      presented very low NIC (<100 mg l-1) and MIC (<1300 mg l-1) values, whereas C.
      cladosporioides and F. oxysporum presented intermediate values. The method has
      the advantage of good repeatability and accuracy, rapid results within 48-72 h,
      growth detection and susceptibility to the antifungal agent for several fungi at
      the same time, and optimal use of microbiological media by using small volumes of
      consumables.

PMID- 29579896
TI  - Molecular interactions and redox effects of carvacrol and thymol on myofibrillar
      proteins using a non-destructive and solvent-free methodological approach.
AB  - The present study provides molecular insight into the effect of thymol and
      carvacrol on the oxidative damage caused to myofibrillar proteins by a hydroxyl
      radical generating system (HRGS). An innovative model system was designed, in
      which gels, prepared with increasing levels of myofibrillar proteins, were
      oxidized by a HRGS (Fe3+/H2O2, 60  degrees C and 7 days) in the presence of
      lipids. The molecular affinity between myofibrillar proteins and both terpenes,
      as well as their effect on the oxidative stability of the gel systems, were
      studied using a non-destructive and solvent-free procedure based on fluorescence
      spectroscopy. Carvacrol displayed more affinity than thymol for establishing
      chemical interactions with protein residues. Both terpenes exhibited a
      significant antioxidant potential against the generation of lipid-derived
      volatile carbonyls and against the formation of protein crosslinking. This
      procedure may be applied to meat products to assess the effectiveness of a given
      antioxidant additive without size reduction or sample processing.

PMID- 29579897
TI  - Quantitative risk assessment of antimicrobials in biosolids applied on
      agricultural land and potential translocation into food.
AB  - The use of biosolids as a fertiliser may be an indirect route for contaminants
      into the food chain. One of the main concerns regarding the spreading of
      biosolids on agricultural land is the potential uptake of contaminants into
      plants which may bio-transfer into grazing animals that supply the food chain
      directly (e.g. meat and milk) and hence are subsequently consumed. The aim of
      this project was to create a quantitative risk assessment model to estimate the
      fate and translocation of triclosan (TCS) and triclocarban (TCC) into the feed
      (grass) and food chain with subsequent human exposure. The model's results
      indicate that TCS and TCC have low potential to transfer into milk and beef
      following the ingestion of contaminated grass by dairy cows. Mean estimated TCS
      and TCC residues in milk and beef show that TCC had the greatest concentration
      (mean values of 7.77*10-6mgkg-1 in milk and 1.36*10-4mgkg-1 in beef). Human
      exposure results show that TCC was greater for milk consumption in infants (1
      4years) (mean value 1.14*10-7mgkg-1bwd-1) and for beef consumption by teens (12
      17years) (mean value 6.87*10-8mgkg-1bwd-1). Concentrations of TCS and TCC were
      well below the estimated acceptable daily intake (ADI). Human health risk was
      estimated by evaluation of the hazard quotient (HQ), which used the NOAEL as a
      toxicity endpoint, combined with milk and beef human exposure estimates. HQ
      results show that all values were <0.01 (no existing risk). A sensitivity
      analysis revealed that the Kow and initial concentration in biosolids as the
      parameters of greatest importance (correlation coefficients 0.91 and 0.19,
      respectively). This highlights the importance of physio-chemical properties of
      the compounds and their detection in biosolids post wastewater treatment along
      with their persistence in soil following application. This model is a valuable
      tool in which to ascertain the potential transfer of contaminants in the
      environment into animal forage with knock on consequences for exposure through
      the human food chain.

PMID- 29579898
TI  - Temperature-pressure-time combinations for the generation of common bean
      microstructures with different starch susceptibilities to hydrolysis.

PMID- 29579899
TI  - Use of Fourier transform infrared spectroscopy for monitoring the shelf life of
      ham slices packed with probiotic supplemented edible films after treatment with
      high pressure processing.
AB  - The aim of the present study was to investigate the potential use of Fourier
      transform infrared (FTIR) spectroscopy to quantify biochemical changes occurring
      in ham slices packed with probiotic supplemented edible films and treated with
      High Pressure Processing (HPP), in monitoring spoilage. Details regarding the
      data collection and experimental procedure were presented by Pavli et al. (2017).
      A series of Partial Least Squares (PLS) models were developed to correlate
      spectral data from FTIR analysis with ham spoilage during storage under vacuum at
      different temperatures (4, 8 and 12 degrees C). FTIR spectra were collected from
      the surface of the ham samples in parallel with microbiological analysis of total
      viable counts (TVC) and lactic acid bacteria (LAB). Qualitative interpretation of
      spectral data was based on a sensory evaluation, using a hedonic scale,
      classifying the samples in three quality classes, fresh, semi-fresh and spoiled.
      The scope of the modeling approach was to discriminate the ham slices in their
      respective quality class and additionally to predict the microbial population
      directly from spectral data. The results obtained demonstrated that the
      processing of the samples affected the performance of classification in the
      sensory classes, with better results observed in the case of for ham slices
      packed with probiotic supplemented (PS) edible films and of control samples
      without HPP. The performance of PLS regression models on providing quantitative
      estimations of microbial counts were based on specific figures of merit (bias
      factor, accuracy factor, root mean square error, percentage of prediction error).
      Bias and accuracy factors were close to unity for both microbial groups tested
      for samples without HPP, whereas for HPP treated samples the values of these
      indices ranged from 0.963 to 1.332, depending on the case and indice. The results
      of this study demonstrated for the first time that although FTIR can be used
      reliably for the rapid assessment of sliced ham, additional processes such as HPP
      can affect its performance.

PMID- 29579900
TI  - Development of fish-based model systems with various microstructures.
AB  - The effectiveness of predictive microbiology is limited by the lack of knowledge
      concerning the influence of food microstructure on microbial dynamics. Therefore,
      future modelling attempts should be based on experiments in structured food model
      systems as well as liquid systems. In this study, fish-based model systems with
      various microstructures were developed, i.e., two liquid systems (with and
      without xanthan gum), an emulsion, an aqueous gel, and a gelled emulsion. The
      microstructural effect was isolated by minimising compositional and physico
      chemical changes among the different model systems. The systems were suitable for
      common growth and mild thermal inactivation experiments involving both
      homogeneous and surface inoculation. Average pH of the model systems was 6.36+/
      0.03 and average aw was 0.988+/-0.002. The liquid system without xanthan gum
      behaved like a Newtonian fluid, while the emulsion and the liquid containing
      xanthan gum exhibited (non-Newtonian) pseudo-plastic behaviour. Both the aqueous
      gel and gelled emulsion were classified as strong gels, with a hardness of 1.35+/
      0.07N and 1.25+/-0.05N, respectively. Fat droplet size of the emulsion and gelled
      emulsion model systems was evenly distributed around 1MUm. In general, the set of
      model systems was proven to be suitable to study the influence of important
      aspects of food microstructure on microbial dynamics.

PMID- 29579901
TI  - Quantification of Campylobacter jejuni contamination on chicken carcasses in
      France.
AB  - Highly prevalent in poultry, Campylobacter is a foodborne pathogen which remains
      the primary cause of enteritis in humans. Several studies have determined
      prevalence and contamination level of this pathogen throughout the food chain.
      However it is generally performed in a deterministic way without considering
      heterogeneity of contamination level. The purpose of this study was to quantify,
      using probabilistic tools, the contamination level of Campylobacter spp. on
      chicken carcasses after air-chilling step in several slaughterhouses in France.
      From a dataset (530 data) containing censored data (concentration <10CFU/g),
      several factors were considered, including the month of sampling, the farming
      method (standard vs certified) and the sampling area (neck vs leg). All
      probabilistic analyses were performed in R using fitdistrplus, mc2d and nada
      packages. The uncertainty (i.e. error) generated by the presence of censored data
      was small (ca 1 log10) in comparison to the variability (i.e. heterogeneity) of
      contamination level (3 log10 or more), strengthening the probabilistic analysis
      and facilitating result interpretation. The sampling period and sampling area
      (neck/leg) had a significant effect on Campylobacter contamination level. More
      precisely, two "seasons" were distinguished: one from January to May, another one
      from June to December. During the June-to-December season, the mean Campylobacter
      concentration was estimated to 2.6 [2.4; 2.8] log10 (CFU/g) and 1.8 [1.5; 2.0]
      log10 (CFU/g) for neck and leg, respectively. The probability of having
      >1000CFU/g (higher limit of European microbial criterion) was estimated to 35.3%
      and 12.6%, for neck and leg, respectively. In contrast, during January-to-May
      season, the mean contamination level was estimated to 1.0 [0.6; 1.3] log10
      (CFU/g) and 0.6 [0.3; 0.9] log10 (CFU/g) for neck and leg, respectively. The
      probability of having >1000CFU/g was estimated to 13.5% and 2.0% for neck and
      leg, respectively. An accurate quantification of contamination level enables
      industrials to better adapt their processing and hygiene practices. These results
      will also help in refining exposure assessment models.

PMID- 29579902
TI  - Plum (Prunus salicina) peel and pulp microparticles as natural antioxidant
      additives in breast chicken patties.
AB  - Fiber microparticles (MPCs) separately obtained from peel and pulp of Japanese
      plum residues contained co-extracted beta-carotene, lutein, and alpha- and gamma
      tocopherols, as well as polyphenols (cyanidins, quercetin derivatives, pentameric
      proanthocyanidins). Peel and pulp MPCs were then separately evaluated as natural
      antioxidant additives (2.0% w/w level) in raw breast chicken patty, susceptible
      to oxidation. Their effect on technological properties was also analyzed. MPCs
      reduced in 50% the formation of thiobarbituric acid reactive substances (TBARS)
      in raw patties during 10-days storage at 4.0 degrees C. Ferric reducing power
      (FRAP) was 77-157% higher in MPCs-added patties, especially with peel MPCs, being
      then attributed to the antioxidants supplied by these MPCs. It can be also
      associated to the highest alpha- and gamma-tocopherol levels found in the peel
      MPCs-added patties, which remained high after cooking as well. Also, higher
      pectin and low lignin contents of pulp MPCs determined greater hydration,
      stabilized the cyanidins and, hence, the red color transferred to raw patties,
      and increased springiness of cooked patties. Plum peel and pulp MPCs are
      efficient additives for chicken meat products.

PMID- 29579903
TI  - Berries extracts as natural antioxidants in meat products: A review.
AB  - The aim was to evaluate antioxidants from berries as replacement food additives
      for inhibition of lipid and protein oxidation in meat and meat products, since
      meats are highly susceptible to oxidation. Oxidation can be delayed/retarded by
      synthetic antioxidants with phenolic structures (e.g. butylated hydroxytoluene).
      However, new natural alternatives are needed for synthetic antioxidants due to
      the controversy regarding their possible negative health effects and consumers'
      demand for more 'natural' food additives. Berries are a good source of phenolic
      compounds, especially anthocyanins, which can be used as the potential
      alternative. Reviewed berries included bearberry (Arctostaphylos sp.), blueberry
      (Vaccinium sp.), blackberry (Rubus sp.), blackcurrant (Ribes nigrum), cranberry
      (Vaccinium sp.), cloudberry (Rubus chamaemorus), strawberry (Fragaria ananassa),
      and grape berries (Vitis sp.). Data implied that blueberries, blackberries,
      cranberries, and grapes can be useful for replacing/decreasing synthetic
      antioxidants in meat products. Their extracts have antioxidant polyphenols with
      health benefits that are useful for stabilizing meat products.

PMID- 29579904
TI  - Wine tasting based on emotional responses: An expedite approach to distinguish
      between warm and cool climate dry red wine styles.
AB  - In this study, we improved an empirical tasting sheet including emotional
      responses and common sensory attributes. An Optimized Descriptive Profile (ODP)
      was run to characterize different red wines according to sensory descriptors used
      in the improved sheet. A total of 5 wines were evaluated by a Consumer Panel (CP)
      of 103 subjects (36 females, 67 males) using the improved sheet and a Check-All
      That-Apply (CATA) list of 25 emotions. In the ODP, the panel identified the main
      discriminating sensory attributes as "Complexity", "Astringency" and "Duration of
      the wine fragrance". However, this analysis did not allow for differentiating
      very distinct dry red wine styles originating from warmer or cooler regions. On
      the contrary, Principal Component Analysis of emotional attributes demonstrated
      that these two wine styles could be easily distinguished. In particular, wine
      with a red-brick color, complex smell and aggressive mouthfeel consistent with
      those from cooler regions was less liked by the CP than a warm climate gold
      awarded wine. Although receiving lower scores considering its color and smell,
      the former wine was regarded as the most "surprising" in the CATA.

PMID- 29579905
TI  - Parameter estimations in predictive microbiology: Statistically sound modelling
      of the microbial growth rate.
AB  - When building models to describe the effect of environmental conditions on the
      microbial growth rate, parameter estimations can be performed either with a one
      step method, i.e., directly on the cell density measurements, or in a two-step
      method, i.e., via the estimated growth rates. The two-step method is often
      preferred due to its simplicity. The current research demonstrates that the two
      step method is, however, only valid if the correct data transformation is applied
      and a strict experimental protocol is followed for all experiments. Based on a
      simulation study and a mathematical derivation, it was demonstrated that the
      logarithm of the growth rate should be used as a variance stabilizing
      transformation. Moreover, the one-step method leads to a more accurate estimation
      of the model parameters and a better approximation of the confidence intervals on
      the estimated parameters. Therefore, the one-step method is preferred and the two
      step method should be avoided.

PMID- 29579906
TI  - Growth of Listeria monocytogenes in pasteurized vanilla cream pudding as affected
      by storage temperature and the presence of cinnamon extract.
AB  - The objective of the present study was the assessment and quantitative
      description of the growth behavior of Listeria monocytogenes as a function of
      temperature in vanilla cream pudding, formulated with or without cinnamon
      extract. Commercially prepared pasteurized vanilla cream pudding, formulated with
      (0.1% w/w) or without cinnamon extract, was inoculated with a five-strain mixture
      of L. monocytogenes (ca. 2logCFU/g) and stored aerobically at 4, 8, 12 and 16
      degrees C. At appropriate time intervals, L. monocytogenes populations were
      determined, and the primary model of Baranyi and Roberts was fitted to the
      derived microbiological data for the estimation of the pathogen's growth kinetic
      parameters. The effect of temperature on maximum specific growth rate (MUmax) was
      then modeled for each product type using a square-root-type model, and the
      developed models were validated using independent growth data generated during
      storage of inoculated vanilla cream samples under dynamic temperature conditions.
      Although the kinetic behavior of the pathogen was similar in cream with and
      without cinnamon extract during storage at higher temperatures, significant
      (P<0.05) differences were observed between the two product types at 4 degrees C.
      With regard to secondary modelling, the estimated values of Tmin for cream with
      and without cinnamon extract were 0.39 degrees C and -2.54 degrees C,
      respectively, while the dynamic models exhibited satisfactory performance.
      Finally, as demonstrated by the findings of pulsed-field gel electrophoresis,
      both temperature and cinnamon extract affected the pathogen's strains dominating
      during storage. According to the collected data, cinnamon extract exhibits an
      important potential of enhancing the microbiological safety of vanilla cream
      pudding, provided that efficient temperature control is in place. The developed
      models should be useful in quantitative microbial risk assessment regarding the
      studied cream products.

PMID- 29579907
TI  - An interaction model for the combined effect of temperature, pH and water
      activity on the growth rate of E. coli K12.
AB  - Previous research has indicated that more complex model structures than the
      commonly used gamma model are needed to obtain an accurate prediction of the
      effect of multiple environmental conditions on the microbial growth rate. Due to
      the complexity associated with the development of such model structures, it is
      recommended that the model structure is compatible with a modular model building
      method. In this research, a gamma-interaction model was built to describe the
      combined effect of temperature, pH and water activity on the microbial growth
      rate of E. coli K12 based on a dataset of 68 bioreactor experiments. This novel
      interaction model was compared with the standard gamma model. The model
      structures were tested separately for the combined effects of (i) temperature and
      pH, (ii) pH and water activity, (iii) temperature and water activity and (iv)
      temperature, pH and water activity. Based on the results of this research, it was
      concluded that models for the combined effect of environmental conditions need to
      allow for sufficient flexibility for the description of combined effects of
      environmental conditions to obtain accurate model predictions. In the current
      study, this flexibility was successfully introduced by using the gamma
      interaction model. A cross-validation study also demonstrated that the
      predictions of the interaction model are more robust with respect to the specific
      data used than the gamma model. As such, the gamma-interaction model provides
      food producers and food safety authorities with a more accurate and reliable tool
      for the prediction of the microbial growth rate as a function of multiple
      environmental conditions.

PMID- 29579908
TI  - Quantitative microbiological risk assessment in food industry: Theory and
      practical application.
AB  - The objective of this article is to bring scientific background as well as
      practical hints and tips to guide risk assessors and modelers who want to develop
      a quantitative Microbiological Risk Assessment (MRA) in an industrial context.
      MRA aims at determining the public health risk associated with biological hazards
      in a food. Its implementation in industry enables to compare the efficiency of
      different risk reduction measures, and more precisely different operational
      settings, by predicting their effect on the final model output. The first stage
      in MRA is to clearly define the purpose and scope with stakeholders, risk
      assessors and modelers. Then, a probabilistic model is developed; this includes
      schematically three important phases. Firstly, the model structure has to be
      defined, i.e. the connections between different operational processing steps. An
      important step in food industry is the thermal processing leading to microbial
      inactivation. Growth of heat-treated surviving microorganisms and/or post-process
      contamination during storage phase is also important to take into account.
      Secondly, mathematical equations are determined to estimate the change of
      microbial load after each processing step. This phase includes the construction
      of model inputs by collecting data or eliciting experts. Finally, the model
      outputs are obtained by simulation procedures, they have to be interpreted and
      communicated to targeted stakeholders. In this latter phase, tools such as what
      if scenarios provide an essential added value. These different MRA phases are
      illustrated through two examples covering important issues in industry. The first
      one covers process optimization in a food safety context, the second one covers
      shelf-life determination in a food quality context. Although both contexts
      required the same methodology, they do not have the same endpoint: up to the
      human health in the foie gras case-study illustrating here a safety application,
      up to the food portion in the brioche case-study illustrating here a quality
      application.

PMID- 29579909
TI  - Determining quality parameters of fish oils by means of 1H nuclear magnetic
      resonance, mid-infrared, and near-infrared spectroscopy in combination with
      multivariate statistics.
AB  - Fish oil is becoming increasingly popular as a dietary supplement as well as for
      its use in animal feed, which is mainly due to its high contents of the health
      promoting omega-3 fatty acids. However, these polyunsaturated fatty acids are
      highly susceptible to oxidation, which results in a decrease of the fish oil
      quality. This study investigated the potential of 1H NMR, FT-MIR, and FT-NIR
      spectroscopy in the quality assessment of fish oils. A total of 84 different fish
      oils, of which 22 were subjected to accelerated storage with varying temperature
      and light exposure, were used to develop models for predicting the peroxide value
      (PV), the anisidine value (AnV), and the acid value (AV). Predictions were based
      on comprehensive spectroscopic data in combination with Artificial Neural
      Networks (ANN) as well as Partial Least Squares Regression (PLSR). The best ANN
      model for PV was obtained from NMR data, with a predictive coefficient of
      determination (Q2) of 0.961 and a Root Mean Square Error of Prediction (RMSEP) of
      1.5meqO2kg-1. The combined MIR/NIR data provided the most reliable ANN model for
      AnV (Q2=0.993; RMSEP=0.74). For AV, the ANN model based on the MIR data yielded a
      Q2 of 0.988 and an RMSEP of 0.43mgNaOHg-1. In most cases, the accuracy of the ANN
      models was superior to the respective PLSR models. Variable selection and data
      dimensionality reduction turned out to improve the performance of the ANN models
      in some cases. The application of 1H NMR, FT-MIR, and FT-NIR spectroscopy in
      combination with ANN can be considered very promising for a rapid, reliable, and
      sustainable assessment of fish oil quality.

PMID- 29579910
TI  - Effect of dietary fiber (inulin) addition on phenolics and in vitro
      bioaccessibility of tomato sauce.
AB  - The effect of the addition of inulin (5 and 10%) on the phenolic content and in
      vitro gastrointestinal digestion of tomato sauces has been investigated. Results
      have shown that the addition of inulin to tomato sauce significantly decreased
      the total phenolic content (57-68%), total flavonoid content (48-60%), and total
      antioxidant capacity (49-61%). Similarly, all assays of the sauce containing both
      5% and 10% inulin, showed a slight decrease during in vitro gastrointestinal
      digestion of tomato sauces. Higher levels of inulin added to tomato sauce
      resulted in the greatest decrease in phenolic content, probably because of the
      interaction between inulin and phenolic compounds. To address the effects of
      inulin on the global metabolite profile of tomato sauce, an untargeted
      metabolomics approach was followed. Changes related to the presence of inulin
      suggest that inulin quenches a subset of unidentified compounds which are present
      in sauce but not in fruit, suggesting that inulin can contribute to the
      conservation of fruit properties in tomato sauce.

PMID- 29579911
TI  - Aflatoxigenic and ochratoxigenic fungi and their mycotoxins in spices marketed in
      Brazil.
AB  - During their processing, spices usually remain close to the ground for drying, a
      fact that disposes to fungal contamination, as well as moisture transferred from
      the tropical environment can allow their multiplication and synthesis of
      mycotoxins. The objective of this study was to evaluate the presence of
      potentially toxigenic fungi and mycotoxins in spices marketed in Brazil. The
      fungal contamination was evaluated by direct plating for samples of clove, black
      and white peppers. Spread plate was used for the samples of rosemary, cinnamon,
      fennel, pepperoni pepper and oregano. Analyses were performed in triplicate in
      DG18 media with incubation at 25 degrees C for 7days. The isolation and
      identification of fungi followed specific recommendations of culture media and
      incubation period for each genus. The presence of mycotoxins in spices was
      verified by high-performance liquid chromatography (HPLC) coupled to
      fluorescence. The frequency of species potentially toxigenic was high in white
      and black peppers with presence of both aflatoxigenic and ochratoxigenic fungi.
      Only rosemary and fennel showed contamination with aflatoxin B1 and there was a
      positive correlation (rho<0.01) between the rosemary contamination with the
      presence of AFB1 and A. flavus. Even in the presence of ochratoxigenic fungi,
      ochratoxin A was not detected in the samples. The presence of natural components
      with antimicrobial activity could justify the low presence of mycotoxins, even in
      the presence of known toxigenic fungi in the samples. Mycotoxins were not
      detected in spices covered by Brazilian regulation of mycotoxins. On the other
      hand, these contaminants were present in other spices consumed by population and
      not mentioned in the regulation, which could be considered a cause to concern.

PMID- 29579912
TI  - Fungi in cake production chain: Occurrence and evaluation of growth potential in
      different cake formulations during storage.
AB  - This study aimed to determine the prevalence and populations of fungi in cake
      production chain. Besides, the growth potential of twelve fungal strains in
      different cake formulations was evaluated. Raw materials from two different
      batches (n=143), chocolate cakes (n=30), orange cakes (n=20), and processing
      environment air samples (n=147) were analyzed. Among the raw materials, wheat
      flour (3.2+/-0.3 log CFU per g) and corn meal (3.8+/-0.8 log CFU per g) belonging
      to batch #1 showed significant higher fungal counts (p<0.05). The fungal counts
      in the processing environment air reached up to 2.56 log CFU per m3 (p<0.05). The
      predominant fungi species in the industrialized cakes were Aspergillus flavus
      (28.15%), Penicillium citrinum (18.45%), Penicillium paxilli (14.56%), and
      Aspergillus niger (6.8%), which were also detected in the raw materials and
      processing environment air. Only Penicillium glabrum and Penicillium citrinum
      showed visible mycelium (>3mm) in the free of preservative cake formulation at
      19th and 44th days of storage at 25 degrees C, respectively. Revealing the
      biodiversity of fungi in ingredients, air and final products, as well as
      challenging final products with representative fungal strains may assist to
      implement effective controlling measures as well as to gather data for the
      development of more robust cake formulations.

PMID- 29579913
TI  - Absorption kinetics of vitamin E nanoemulsion and green tea microstructures by
      intestinal in situ single perfusion technique in rats.
AB  - The absorption kinetics of food ingredients such as nanoemulsified vitamin E and
      green tea microstructures were evaluated by the intestinal in situ single
      perfusion technique. Absorption rate, sub-acute oral toxicity and organ
      morphology in a rat model were examined. The intestinal in situ single perfusion
      technique and HPLC analysis were applied to investigate the absorption rate of
      selected materials by examining time-dependent changes in the serum levels of
      catechin and dl-alpha-tocopherol. The acute toxicity test and histopathological
      evaluation were applied to analyze the safety of microsized green tea and
      nanosized vitamin E in a rat model. Total serum dl-alpha-tocopherol levels
      significantly increased with nanosized vitamin E administration (P<0.05). Rats
      treated to nanosized vitamin E until 90min after administration showed
      significantly increased absorption rate of serum dl-alpha-tocopherol levels at
      each time point (10min interval) (P<0.001). Rats administered 2000mg/kg of
      nanosized vitamin E and microsized green tea did not show signs of acute toxicity
      or death after 14days of observation. In addition, macroscopic analysis showed
      that there were no changes in representative organ sections of rats following the
      oral administration of food-related nanoscale materials. We successfully
      demonstrated that using nanosized vitamin E increased absorption rate to a
      greater extent than normal food-related material, and these results occurs via
      safety analyses on food-related nanoscale materials for human consumption. These
      results could be useful for the design and development of novel nanoemulsified
      vitamin E and microsized green tea formulations that can overcome the problem of
      their bioavailability and improve their efficacy while still maintaining their
      essential therapeutic efficacies.

PMID- 29579914
TI  - Characterization of taste and aroma compounds in Tianyou, a traditional fermented
      wheat flour condiment.
AB  - Taste and aroma compounds in Tianyou were determined using HPLC and GC-MS/GC
      olfactometry. By comparison with light soy sauce (control), the contents of salt,
      sugar, total nitrogen and total acid in Tianyou were higher, while the contents
      of umami, sweet and bitter free amino acids, and the percentage of 1-5kDa
      peptides in Tianyou were lower. Thirty-one aroma-active compounds were identified
      in both Tianyou and the control (30 compounds in common). Aroma extraction
      dilution analysis indicated that most flavor dilution factors of aroma-active
      compounds were lower in Tianyou than the control. Quantitative descriptive
      analysis showed that Tianyou had significantly stronger salty and sweet tastes,
      weaker umami taste and weaker malty, caramel-like and smoky notes when compared
      to the control (p<0.05), which were in agreement with the analyses of taste and
      aroma compounds. This confirms that Tianyou has a distinctively different flavor
      from light soy sauce.

PMID- 29579915
TI  - Specialized oxygenated heterocyclics from Villorita cyprinoides with
      cyclooxygenase-2 and 5-lipoxygenase inhibitory properties.
AB  - Villorita cyprinoides is traditional seafood in the coastal regions of Arabian
      Sea. Bioactivity-guided purification of ethyl acetate:methanol extract of V.
      cyprinoides resulted in the identification of two O-spirocyclic ether derivatives
      (1-2) along with one O-heterocyclic irregular meroterpenoid (3). The structures
      and their relative stereochemistries were elucidated through comprehensive
      spectroscopic experiments. These specialized metabolites were found to exhibit
      potential antioxidative (IC50<0.70mg/mL) and anti-inflammatory activities against
      pro-inflammatory inducible 5-lipoxygenase (anti-5-LOX IC50<=0.80mg/mL) and
      cyclooxygenase-2 (anti-COX-2 IC50<0.75mg/mL) enzymes. Molecular docking
      simulations were used to describe the interactions of the isolated compounds
      (ligands) with COX-2 and 5-LOX inflammation model. The permissible hydrophobic
      hydrophilic balance and lesser steric bulk of spirocyclic ether derivative
      (compound 2), along with greater number of hydrogen bonding interactions in the
      active sites of COX-2 and 5-LOX manifested towards its greater bioactivities
      compared to other compounds isolated from V. cyprinoides.

PMID- 29579916
TI  - Effect of technological treatments on bovine lactoferrin: An overview.
AB  - Lactoferrin (LF) is a multifunctional protein that exerts important activities in
      the neonate through its presence in milk, and also in other external mucosas,
      acting as a defense protein of innate immunity. The addition of bovine LF to
      infant formula and also to other functional products and cosmetics has increased
      during the last decades. Consequently, it is essential to know the effect that
      the technological processes, necessary to elaborate those products, have on LF
      activity. In this study, we have revised the effect of classical treatments on
      lactoferrin structure and activity, such as heat treatment or drying, and also of
      emerging technologies, like high pressure or pulsed electric field. The results
      of the studies included in this review indicate that LF stability is dependent on
      its level of iron-saturation and on the characteristics of the treatment media.
      Furthermore, the studies revised here reveal that the non-thermal treatments are
      interesting alternatives to the traditional ones, as they protect better the
      structure and activity of lactoferrin. It is also clear the need for research on
      LF encapsulation by different ways, to protect its properties before it reaches
      the intestine. All this knowledge would allow designing processes less harmful
      for LF, thus maintaining all its functionality.

PMID- 29579917
TI  - Factors affecting migration kinetics from a generic epoxy-phenolic food can
      coating system.
AB  - This study investigated how the properties of a polymeric can coating film, such
      as thickness and crosslink density as well as the type of migrant, influence the
      migration kinetics of model migrants in an attempt to better understand, model
      and control the migration process. Four model migrants were used BADGE (bisphenol
      A diglycidyl ether), BADGE.H2O, cyclo-diBADGE and Uvitex OB, that differ in size
      and polarity. Fatty and aqueous food simulants were used at high temperatures (70
      130 degrees C). The apparent diffusion coefficients were found to decrease with
      increasing crosslink density, while they increased with increasing film
      thickness. The apparent activation energy of BADGE and BADGE-related compounds
      was calculated from the diffusion data and were high, in the range of 250
      264kJmol-1. The polarity of the simulant and the polarity of the migrant were
      found to influence migration. The results can be used to improve existing
      migration models, and thereby help to reduce migration from packaging into food
      by using safety-by-design approaches in new product development.

PMID- 29579919
TI  - Extensional and shear rheology of okra hydrocolloid-saliva mixtures.
AB  - This is an investigation of the shear and extensional properties of okra
      polysaccharide-saliva mixtures, intended to model the mechanical behavior a food
      hydrocolloid during oral processing. Shear measurements show that incorporation
      of okra mucilage in saliva interferes with the self-assembly of salivary mucins,
      with partly detrimental effects on the low-shear viscosity of the mixture. This
      is counter-acted by excluded volume effects, as the overall concentration of
      macromolecules in the mixture reaches the semi-dilute regime. Particle tracking
      confirms the lack of direct interactions between the two polymeric populations.
      The contribution of extensional viscosity to the overall behavior of okra
      hydrocolloid-saliva mixtures is dominant, at about one to two orders of size
      higher than the equivalent shear values. The Trouton ratio values are in the
      order of tens or hundreds for the range of concentrations and deformation rates
      under study. Although the extensional viscosity dominates viscous flow, the two
      types of flow are equally important concerning the elastic behavior, giving
      insight on the mechanical behavior of mucilages in the oral cavity.

PMID- 29579918
TI  - Non-destructive analysis of sucrose, caffeine and trigonelline on single green
      coffee beans by hyperspectral imaging.
AB  - Hyperspectral imaging (HSI) is a novel technology for the food sector that
      enables rapid non-contact analysis of food materials. HSI was applied for the
      first time to whole green coffee beans, at a single seed level, for quantitative
      prediction of sucrose, caffeine and trigonelline content. In addition, the intra
      bean distribution of coffee constituents was analysed in Arabica and Robusta
      coffees on a large sample set from 12 countries, using a total of 260 samples.
      Individual green coffee beans were scanned by reflectance HSI (980-2500nm) and
      then the concentration of sucrose, caffeine and trigonelline analysed with a
      reference method (HPLC-MS). Quantitative prediction models were subsequently
      built using Partial Least Squares (PLS) regression. Large variations in sucrose,
      caffeine and trigonelline were found between different species and origin, but
      also within beans from the same batch. It was shown that estimation of sucrose
      content is possible for screening purposes (R2=0.65; prediction error of ~0.7%
      w/w coffee, with observed range of ~6.5%), while the performance of the PLS model
      was better for caffeine and trigonelline prediction (R2=0.85 and R2=0.82,
      respectively; prediction errors of 0.2 and 0.1%, on a range of 2.3 and 1.1% w/w
      coffee, respectively). The prediction error is acceptable mainly for laboratory
      applications, with the potential application to breeding programmes and for
      screening purposes for the food industry. The spatial distribution of coffee
      constituents was also successfully visualised for single beans and this enabled
      mapping of the analytes across the bean structure at single pixel level.

PMID- 29579920
TI  - Effects of cocoa butter triacylglycerides and minor compounds on oil migration.
AB  - In a multi-component chocolate product, oil migration, from high oil content
      filling into chocolate, is one of the major contributors to the product quality
      loss. Among various parameters influencing oil diffusivity, cocoa butter is
      studied intensively. Studies have shown that the rate of oil transportion in
      cocoa butter is affected by its composition, the way that it is crystallized, and
      also the storage conditions. To model and study effects of cocoa butter type and
      processing conditions on oil migration, five different cocoa butter samples were
      studied in this work. Samples' chemical compositions in addition to their
      structural properties were analyzed to understand and compare oil migrations in
      the networks. Crystallized cocoa butter samples were placed in contact with a
      cream as a source of liquid oil. Using Magnetic Resonance Imaging, the movement
      of liquid oil into samples was investigated. The effects of minor differences in
      the cocoa butter chemical compositions on oil migrations rate are shown clearly.
      The highest effective diffusion coefficient was observed in the sample with the
      higher unsaturated fatty acids and phospholipids content. Although shearing at
      250s-1 delayed oil migration in all the samples and a significantly lower
      diffusion coefficient was observed in the dynamic samples, the effects of
      chemical composition were still dominant. This study successfully highlighted
      that even minor differences in cocoa butter composition affect the network mass
      transfer phenomenon dramatically and that it is not easy to diminish these
      possessions by just crystallization processes.

PMID- 29579921
TI  - Changes in the volatile profile of Pinot noir wines caused by Patagonian
      Lactobacillus plantarum and Oenococcus oeni strains.
AB  - The ability of Patagonian L. plantarum and O. oeni strains to change the volatile
      profile of a sterile Pinot noir wine was studied through fermentation assays, at
      laboratory scale. Two strains of each LAB species were selected based on data
      regarding to their ability to survive in wine and to consume l-malic acid. Both
      O. oeni strains but only one L. plantarum (UNQLp 11) strain were able to remain
      viable, consuming l-malic acid through the fermentation assay with a concomitant
      increase of l-lactic acid. The volatile profile of Pinot noir wine, before and
      after LAB inoculation, was measured by using HS-SPME gas chromatography
      technique. This analysis showed that alcohols were the main volatile compounds
      after alcoholic fermentation and that after fermentation with the selected LAB
      strains, a decrease in the volatile alcohols concentration and an increase in the
      volatile esters concentration could be observed. The O. oeni UNQOe 73.2 strain
      produced the most notable change in the volatile profile, with the production of
      some important odorant esters at higher concentration, compared to O. oeni UNQOe
      31b strain. Although, L. plantarum UNQLp 11 strain showed a better performance in
      the consumption of l-malic acid, this strain had a low capacity to modify the
      volatile compounds profile after incubation in red wine. The results found in the
      present work showed that different strains selected as potential malolactic
      starters could have different behavior when are incubated in real wine. Although
      L. plantarum UNQLp 11 strain showed a good consumption of l-malic acid, the O.
      oeni UNQOe 73.2 strain exhibited superior capacity to improve the flavor of wine
      due to its esterase activity that produce an increase of fruity and creamy
      odorants.

PMID- 29579922
TI  - MLVA subtyping of Listeria monocytogenes isolates from meat products and meat
      processing plants.
AB  - Listeria monocytogenes is widely distributed in meat products and the meat
      processing industry thus posing a risk to consumers. The aim of this study was to
      evaluate the suitability of the multilocus variable-number tandem-repeat analysis
      (MLVA) for use as a L. monocytogenes subtyping technique for surveillance and
      routine control in meat products and meat processing plants. A collection of 113
      isolates (including control strains and isolates from meat products and meat
      processing plants) were subject to MLVA analysis using two different platforms
      for fragment sizing: 1.) ABI 3730xl DNA analyzer (Life Technologies) as the
      reference method and 2.) The QIAxcel Advanced System (Qiagen). Although
      discrepancies in fragment sizing were observed it was possible to standardize
      results in order to assign the same allele for a given fragment independently of
      the platform used for fragment sizing. A total of 27 different MLVA profiles were
      obtained considering all the isolates (N=113), 24 of them corresponding to the
      meat industry isolates (N=106). MLVA and multilocus sequence typing (MLST)
      results were compared and yielded Simpson's diversity indices of 0.907 and 0.872,
      respectively. The congruence between both typing methods was measured with the
      adjusted Wallace coefficient (AW). Using MLVA as the primary method, AW=0.946
      suggested that MLVA can predict the sequence type with high accuracy. Given its
      discriminatory power and high throughput, MLVA could be considered a rapid,
      reliable, and high-throughput alternative to existing subtyping methods for
      surveillance and control of L. monocytogenes in the meat-processing industry.

PMID- 29579923
TI  - A metabolic fingerprinting approach based on selected ion flow tube mass
      spectrometry (SIFT-MS) and chemometrics: A reliable tool for Mediterranean origin
      labeled olive oils authentication.
AB  - Selected Ion flow tube mass spectrometry (SIFT-MS) in combination with
      chemometrics was used to authenticate the geographical origin of Mediterranean
      virgin olive oils (VOOs) produced under geographical origin labels. In
      particular, 130 oil samples from six different Mediterranean regions (Kalamata
      (Greece); Toscana (Italy); Meknes and Tyout (Morocco); and Priego de Cordoba and
      Baena (Spain)) were considered. The headspace volatile fingerprints were measured
      by SIFT-MS in full scan with H3O+, NO+ and O2+ as precursor ions and the results
      were subjected to chemometric treatments. Principal Component Analysis (PCA) was
      used for preliminary multivariate data analysis and Partial Least Squares
      Discriminant Analysis (PLS-DA) was applied to build different models (considering
      the three reagent ions) to classify samples according to the country of origin
      and regions (within the same country). The multi-class PLS-DA models showed very
      good performance in terms of fitting accuracy (98.90-100%) and prediction
      accuracy (96.70-100% accuracy for cross validation and 97.30-100% accuracy for
      external validation (test set)). Considering the two-class PLS-DA models, the one
      for the Spanish samples showed 100% sensitivity, specificity and accuracy in
      calibration, cross validation and external validation; the model for Moroccan
      oils also showed very satisfactory results (with perfect scores for almost every
      parameter in all the cases).

PMID- 29579924
TI  - Unlocking Phacelia tanacetifolia Benth. honey characterization through
      melissopalynological analysis, color determination and volatiles chemical
      profiling.
AB  - Phacelia tanacetifolia Benth. honey (14 samples) collected in Poland was
      characterized by melissopalynological analysis, color determination (CIE
      L*a*b*Cab*hab degrees  coordinates) and volatiles (VOCs) composition. VOCs were
      isolated by headspace solid-phase microextraction (HS-SPME, two fibers) and
      ultrasound-assisted solvent extraction (USE, two solvents) and analyzed by GC-MS.
      Principal component analysis (PCA) and hierarchical-tree clustering (HTC) were
      applied to show trends and form groups and to indicate the most representative
      unifloral samples. Six samples were pointed out with average pollen 74.9% and
      color parameters (L=85.1; a*=-0.8; b*=27.9; Cab*=27.9; hab*=91.9) that were
      significantly correlated. High abundance of trans-linalool oxide (27.3-45.9%)
      that was significantly correlated with the pollen percentages, hexan-1-ol (4.4
      5.7%) and lavender lactone (0.8% - 1.5%) were characteristic for their headspace.
      C13-norisoprenoids, mainly (E)-/(Z)-3-oxo-retro-alpha-ionol (4.7-5.4%; 6.9-9.4%)
      and vomifoliol (9.0-13.0%) dominated in their USE extracts.

PMID- 29579925
TI  - Impact of starter culture, ingredients, and flour type on sourdough bread
      volatiles as monitored by selected ion flow tube-mass spectrometry.
AB  - This study deals with the detection of volatile compounds originating from the
      crumb of breads made with sourdoughs obtained through starter culture-initiated
      fermentations, which differed in flour type (wheat and teff), ingredients
      (citrate and malate), fermentation time (24h or 72h), and starter culture strains
      (homo- and heterofermentative lactic acid bacteria species and acetic acid
      bacteria species) applied. Therefore, selected ion flow tube-mass spectrometry
      (SIFT-MS) was used. SIFT-MS is an easy-to-use and promising technique in the
      field of food and flavor analysis. Volatile compounds of crumb samples from the
      breads with sourdough were measured and compared with those of reference bread
      crumb samples. In general, sourdough addition had a positive effect on the
      concentrations of the volatile compounds measured by SIFT-MS. Furthermore, a
      trend toward higher concentrations of several volatiles was seen upon the
      addition of sourdoughs that were fermented up to 72h, compared to the addition of
      sourdoughs that were fermented for a shorter time. Ethanol was the major volatile
      compound identified tentatively, next to alcohols, aldehydes, esters, terpenes,
      and heterocyclic compounds. Also acetoin/ethyl acetate could be identified, but
      these compounds could not be distinguished. Higher alcohols showed an increase
      upon the use of sourdough fermented for a long time. High concentrations of
      acetic acid were found in breads made with Gluconobacter oxydans IMDO A845
      initiated sourdough, indicating its potential for sourdough production. Breads
      made with teff sourdoughs were distinct from wheat-based sourdough breads as to
      their volatile compound profiles.

PMID- 29579926
TI  - An 1H NMR-based metabolomic approach to compare the chemical profiling of retail
      samples of ground roasted and instant coffees.
AB  - The present non-targeted 1H NMR-based fingerprinting approach along with
      multivariate analysis established differences between representative aqueous
      extracts of commercial ground roasted coffee (GRC) and instant (soluble) coffee
      (IC) samples. The latter were prepared either by spray drying or freeze drying.
      When comparing a total of 33 compounds between GRC and IC, the latter product
      contained a remarkable increase in 5-(hydroxymethyl)furfural and carbohydrates,
      as well as a clear decrease in trigonelline, N-methylpyridinium, caffeine,
      caffeoylquinic acids and 2-furylmethanol. Furthermore, the current protocol was
      able to detect the subtle chemical differences between spray-dried and freeze
      dried IC. The aforementioned metabolites could serve as target molecules in the
      attempt to preserve, as much as possible, the organoleptic and nutraceutical
      properties of GRC during the industrial drying processes used in the production
      of the two commercial types of IC.

PMID- 29579927
TI  - Recovery of soluble proteins from migratory locust (Locusta migratoria) and
      characterisation of their compositional and techno-functional properties.
AB  - Edible insects emerged as an alternative source of high-quality proteins.
      Therefore, the effect of an extraction procedure for the recovery of migratory
      locust (Locusta migratoria) protein concentrate (MLPC) on the compositional
      characteristics and techno-functional properties was studied. The influence of pH
      value (2-10) and salt concentration (0, 1 and 3% w/v) on techno-functional
      properties was evaluated. Proteins were identified and characterized by RP-HPLC,
      SDS-PAGE and LC-MS/MS. The initial crude protein content of the whole locusts
      (65.9% on dry base) could be enhanced to 82.3% (MLPC). Solubility profiles of
      MLPC showed maximum solubility at pH9 (100%). Promising functionality comparable
      to egg white protein in terms of emulsifying activity at pH5, foamability at pH3
      and 3% NaCl, and foam stability at pH9 were found. Consequently, MLPC offers a
      nutritious protein source with good functional properties at certain conditions,
      which could be used as food ingredient in a variety of food systems.

PMID- 29579928
TI  - Thymol/cyclodextrin inclusion complex nanofibrous webs: Enhanced water
      solubility, high thermal stability and antioxidant property of thymol.
AB  - The development of novel nanomaterials that provide an efficient encapsulation
      and protection for the active food additives is one of the main focuses of
      current research efforts at food application areas. From this point of view, in
      this study, nanofibrous webs from inclusion complexes (IC) of modified
      cyclodextrins (hydroxypropyl-beta-cyclodextrin (HPbetaCD), hydroxypropyl-gamma
      cyclodextrin (HPgammaCD) and methyl-beta-cyclodextrin (MbetaCD)) and essential
      oils compound (i.e. thymol) was produced through electrospinning technique. While
      pure thymol has a highly volatile nature, the volatility of thymol was
      effectively suppressed by the inclusion complexation and ~88-100% (w/w) of thymol
      was preserved in electrospun thymol/cyclodextrin inclusion complex nanofibers
      (Thymol/CD-IC NF). The aqueous solubility enhancement for hydrophobic thymol was
      demonstrated by phase solubility diagram which also suggested the 1:1M inclusion
      complexation between thymol and CD molecules. Besides, Thymol/CD-IC NF displayed
      quite fast disintegration in water compared to poorly water soluble thymol. By
      inclusion complexation, high temperature stability for volatile thymol was
      achieved for Thymol/CD-IC NF samples. The loading of thymol in Thymol/CD-IC NF
      conferred DPPH radical scavenging ability to these nanofibrous webs. So, the
      Thymol/CD-IC NF have shown antioxidant activity along with enhanced water
      solubility and high thermal stability of thymol. In brief, encapsulation of
      essential oil compounds such as thymol in electrospun CD-IC nanofibers can
      promote its potential application in food and oral-care products by associating
      the large surface area of nanofibrous webs along with CD inclusion complexation
      which provides enhanced water solubility and antioxidant property, and high
      temperature stability for thymol.

PMID- 29579929
TI  - Evaluation of the Pivot Profile(c), a new method to characterize a large variety
      of a single product: Case study on honeys from around the world.
AB  - Honey is a natural product with very diverse sensory attributes that are
      influenced by the flower source, the bee species, the geographic origin, the
      treatments and conditions during storage. This study aimed at describing 50
      honeys from diverse flower sources in different continents and islands, stored
      under various conditions. Many articles have been published on the sensory
      characterization of honeys, thus a common list of attributes has been
      established, but it appeared to be poorly suited to describe a large number of
      honeys from around the world. This is why the novel and rapid sensory evaluation
      method, the Pivot Profile(c), was tested, with the participation of 15 panelists
      during five sessions. The first objective was to obtain a sensory description of
      the 50 honeys that were tested. From 1152 distinct terms, a list of 29 sensory
      attributes was established and the attributes divided into three categories:
      color/texture (8 terms), aroma (16 terms), and taste (5 terms). At first, the
      honeys have been ranked according to their level of crystallization from
      fluid/liquid to viscous/hard. Then color was the second assessment factor of the
      variability. In terms of aroma, honeys from Africa were characterized by smoky,
      resin, caramel and dried fruit as opposed to floral and fruity, mainly for honeys
      from South America and Europe. Finally, the honeys were ranked according to their
      sweetness. The second objective of this study was to test the new sensory method,
      called Pivot Profile(c) which is used to describe a large number of products with
      interpretable results.

PMID- 29579930
TI  - Antioxidative and antibacterial activities of aqueous ethanol extracts of
      berries, leaves, and branches of berry plants.
AB  - Phenolic compounds were extracted with food grade solvent of acidified aqueous
      ethanol from leaves, berries, berry press cakes, and branches of Finnish berry
      plants and analyzed with HPLC-DAD, UPLC-DAD-ESI-MS and NMR. In addition, press
      cakes from two berry species and branches from one species were also extracted
      and analyzed with the same methods. The antioxidant activities of the extracts
      were evaluated using Folin-Ciocalteau, oxygen radical absorbance capacity (ORAC),
      DPPH free radical scavenging, and total radical trapping antioxidant parameter
      (TRAP) assays. The antibacterial activities were investigated against various
      Gram-negative and Gram-positive foodborne pathogens. The leaf extracts showed
      higher antioxidative activities (3-20 fold in ORAC assay, 10-20 fold in TRAP)
      than the berry extracts, in association with the higher contents of phenolic
      compounds in the leaf extracts; Strongest anti-bacterial effects was observed in
      the leaf extracts of lingonberry (Vaccinium vitis-idaea), sea buckthorn
      (Hippophae rhamnoides ssp. rhamnoides) and saskatoon (Amelanchier alnifolia) on
      Staphylococcus aureus, Listeria monocytogenes, and Bacillus cereus. However, the
      antibacterial efficacy varied with bacterial species and strains. The Folin
      Ciocalteu, ORAC, and TRAP values was strongly correlated with the total content
      of flavonoids with less association shown with the content of total phenolics and
      flavonol glycosides. The results suggest a major contribution of pranthocyanidins
      and flavan-3-ols to the antioxidative activities of the extracts. The growth
      inhibition on Staphylococcus aureus and Bacillus cereus was clearly associated
      with the content of total phenolics and ellagitannins.

PMID- 29579931
TI  - Sensory profiling and quality assessment of research Cabernet Sauvignon and
      Chardonnay wines; quality discrimination depends on greater differences in
      multiple modalities.
AB  - The sensory profiles of Cabernet Sauvignon and Chardonnay research wines were
      determined and analysed together with wine quality scores of expert judges.
      Research Cabernet Sauvignon and Chardonnay wines from three and two vintages,
      respectively, were evaluated. Wines of both varieties were produced with grapes
      harvested from across South Australian wine making regions throughout 2013-2016
      vintages. Wines within varieties were vinified identically across samples and
      also across vintages. Wines were profiled in triplicate using descriptive
      analysis with a panel of trained assessors (n=9-11) and graded for quality in
      triplicate by winemakers (n=6-9) using a sorting task based on similarity of
      quality and with the aid of definitions formed by the winemakers prior to
      sorting. The data sets were analysed using canonical variate analysis (CVA) and
      multidimensional scaling (MDS). The scores from CVA and MDS per variety per
      vintage were analysed using Generalised Procrustes Analysis (GPA). Differences in
      Cabernet Sauvignon samples by provenance were determined, where associations with
      regions by sensory attributes were observed in all vintages. These wines were
      consistently sorted based on quality by the winemakers, evident from GPA.
      Chardonnay in comparison were poorly discriminated in both sensory profiles and
      quality. The combination of descriptive sensory analysis with sorting was
      complimentary to each other and was able to uncover additional information about
      the sensory properties of wines when the two methods were used in concert, such
      as balance and complexity. However the red wine variety had more intrinsic
      characteristics that lead to better discrimination based on sensory properties
      and hence quality than the white wine variety.

PMID- 29579932
TI  - Multi-functional application of Moringa oleifera Lam. in nutrition and animal
      food products: A review.
AB  - Research on the use of various parts of the Moringa oleifera Lam. plant (M.
      oleifera) as a nutritional and neutraceutical resource for human and animal diets
      has increased in recent years, emanating from the widespread use of the plant in
      traditional cuisines and medicinal remedies in several regions of the world.
      Analytical studies have identified M. oleifera as an important source of
      essential nutrients; rich in protein, essential amino acids, minerals, and
      vitamins, with a relatively low amount of antinutrients. It is also a rich source
      of other bio active compounds including flavonoids and phenolic compounds; with
      several studies detailing demonstrated in vitro and in vivo functional
      properties, most substantially, antioxidant activities. Moringa oleifera
      consumption has been reported to improve the health status, feed conversion
      efficiency, growth performance and product quality of several livestock species,
      at dietary inclusion rates generally not exceeding 5% of total dry matter intake.
      Fortification of processed foods with M. oleifera has been reported to increase
      nutritional value, some organoleptic properties, oxidative stability and product
      shelf life; with a notable need for further analytical and consumer studies in
      the development of these products. There is a paucity of literature detailing
      clinical studies, nutrient bioavailability, toxicity and the mode of action of
      the bioactive compounds to which the health claims associated with M. oleifera
      consumption are attributed. Many of these are not yet fully understood; therefore
      more research in these areas is required in order to fully utilize the potential
      benefits of this plant in human and livestock nutrition.

PMID- 29579933
TI  - Portulaca oleracea extracts and their active compounds ameliorate inflammatory
      bowel diseases in vitro and in vivo by modulating TNF-alpha, IL-6 and IL-1beta
      signalling.
AB  - Portulaca oleracea L. (P. oleracea) is an herb that is widely used in traditional
      medicine to treat various diseases. However, its effects on inflammatory
      diseases, such as inflammatory bowel disease (IBD), are not yet well
      characterized. Here, we investigated the impact of the ethyl acetate (EtOAc) and
      ethanol (EtOH) extracts of P. oleracea on lipopolysaccharide (LPS)-induced
      inflammatory responses and phosphorylation of ERK, JNK, and p38 expression in
      RAW264.7 macrophages. In addition, the inhibitory effects of these extracts and
      fractions on 3% dextran sulphate sodium (DSS)-induced ulcerative colitis were
      examined using an ICR mouse model. DSS-induced colitis, including body weight
      loss, reduced colon length, and histological colon injury, was significantly
      ameliorated in mice fed the P. oleracea extracts (200 and 500mg/kg). In
      particular, P. oleracea extracts also inhibited pro-inflammatory cytokine (TNF
      alpha, IL-6, and 1L-1beta) production in mice with DSS-induced colitis; the P.
      oleracea extracts displayed higher and/or similar inhibitory activity to
      sulfasalazine at high concentrations. Furthermore, the chemical structures of
      active compounds separated from the EtOAc extract of P. oleracea were elucidated
      using nuclear magnetic resonance (NMR) spectroscopy (see Figure in supplementary
      materials), resulting in the identification of three known compounds. Among these
      active compounds, cis-N-feruloyl-3'-methoxytyramine (2) exhibited the strongest
      effects on preventing DSS-induced IBD in animal models. Thus, extract of P.
      oleracea and their active compounds represents a new therapeutic approach for
      patients with inflammatory bowel diseases.

PMID- 29579934
TI  - In vitro protein digestion of pork cuts differ with muscle type.
AB  - Porcine trapezius, longissimus dorsi and biceps femoris muscles have been shown
      to contain different types of muscle fibers. Little is known about the
      differences in digestibility among cooked pork cuts. In this study, we compared
      the protein losses of porcine trapezius, longissimus dorsi and biceps femoris
      muscles under in vitro digestion conditions. Meat samples were cooked in 72
      degrees C water bath to center temperature of 70 degrees C. Then meat samples
      were homogenized and incubated with pepsin alone or followed by trypsin. The in
      vitro protein losses and particle size were measured. The pepsin and trypsin
      digestion products were separated and identified by SDS-PAGE and Nano LC-LTQ
      Orbitrap XL MS/MS. The results indicated that longissimus dorsi muscle had the
      highest losses under both pepsin and trypsin treatments (P<0.05). In untreated
      samples, biceps femoris muscle showed the greatest particle size (P<0.05), but
      enzymatic treatment decreased particles to the similar size for all the three
      muscles (P>0.05). Proteome analysis indicated that biceps femoris muscle had the
      highest susceptibility to digestion. Interaction analysis reveals that
      differential proteins mainly are related to glycolysis and muscle contraction.
      And thus fiber types could be the key factor to cause the differences in protein
      composition and their susceptibility to digestion.

PMID- 29579935
TI  - Characterization of oat beta-glucan and coenzyme Q10-loaded beta-glucan powders
      generated by the pressurized gas-expanded liquid (PGX) technology.
AB  - The physicochemical properties of the oat beta-glucan powder (BG) and coenzyme
      Q10 (CoQ10)-loaded BG powder (L-BG) produced by the pressurized gas-expanded
      liquid (PGX) technology were studied. Helium ion microscope, differential
      scanning calorimeter, X-ray diffractometer, AutoSorb iQ and rheometer were used
      to determine the particle morphology, thermal properties, crystallinity, surface
      area and viscosity, respectively. Both BG (7.7MUm) and L-BG (6.1MUm) were
      produced as micrometer-scale particles, while CoQ10 nanoparticles (92nm) were
      adsorbed on the porous structure of L-BG. CoQ10 was successfully loaded onto BG
      using the PGX process via adsorptive precipitation mainly in its amorphous form.
      Viscosity of BG and L-BG solutions (0.15%, 0.2%, 0.3% w/v) displayed Newtonian
      behavior with increasing shear rate but decreased with temperature. Detailed
      characterization of the physicochemical properties of combination ingredients
      like L-BG will lead to the development of novel functional food and natural
      health product applications.

PMID- 29579936
TI  - Effect of ultrasound on the physicochemical and microbiological characteristics
      of Italian salami.
AB  - Italian salami were sonicated in different times (0, 3, 6 and 9min) using
      ultrasound bath (US, 25kHz). The effect of sonication on microbial growth (lactic
      acid bacteria and Micrococcaceae), lipid and protein oxidation, total heme
      pigments (THP), non heme iron (NHI) and metmyoglobin (MMb) was investigated
      during processing (0, 2, 15, and 28days) and storage (1, 30, and 120days). US
      enhanced growth of microorganisms (P<0.05), mainly for the treatment 9min of
      sonication. The lipid (peroxide value and TBARS) and protein (thiol group)
      oxidative reactions were accelerated by US (P<0.05) and they should be considered
      to maintain Italian salami quality. Sonication contributed to maintenance of THP
      (P<0.05), especially during storage. MMb pigment was not affected by sonication
      (P>0.05). This study presented some features of US application that could be
      explored in the manufacture of Italian salami.

PMID- 29579937
TI  - Volatile changes in cv. Verdeal Transmontana olive oil: From the drupe to the
      table, including storage.
AB  - This study focused on the volatile changes in cv. Verdeal Transmontana throughout
      the entire olive oil processing chain, from the drupe to olive oil storage up to
      12 months, while correlating it with quality parameters and sensory quality.
      During crushing and malaxation, the volatiles formed were mainly "green-leaf
      volatiles" (GLVs), namely (E)-2-hexenal, hexanal, and 1-hexanol. Centrifugation
      and clarification steps increased the total volatile amounts to 130 mg kg-1.
      However, clarification also increased nonanal and (E)-2-decenal contents, two
      markers of oxidation, with a noticeable loss of phenolic compounds and oxidative
      stability. During storage, the total volatile amounts reduced drastically (94% at
      12 months after extraction), together with the positive sensory attributes
      fruity, green, bitter, and pungent. Despite being classified as extra-virgin
      after one year of storage, peroxides and conjugated dienes were significantly
      higher while there was a reduction in antioxidant capacity as well as in phenolic
      compounds (less 50%) and oxidative stability (57%). The present work allowed
      concluding that the extraction process modulates the volatile composition of
      olive oil, with a concentration of volatiles at the clarification step. During
      storage, volatiles are lost, mainly eight months after extraction, leading to the
      loss of important sensory attributes.

PMID- 29579938
TI  - Patterns of sweetness preference in red wine according to consumer
      characterisation.
AB  - The preference for sweet taste in red wine was examined according to consumer
      categories of age, gender, drinking experience and personality type (Big-5
      personality-test). A total of 114 subjects revealed their preferences for
      sweetness after tasting dry red wine spiked with equal concentrations of glucose
      and fructose at 2g/L, 4g/L, 8g/L, 16g/L and 32g/L, following an ascending forced
      choice paired comparison method (2-AFC). The overall preference for sweetness was
      shown within the range of 4.8 to 21.9g/L, with maximal liking at 8g/L. Three
      patterns of response to sweetness were observed (sweet dislikers, sweet likers
      and indifferent to sweet) according to the different categories of consumers.
      Differences (p>0.05) were not found in sweetness preference among the categories
      up to 16g/L sugar except for the trait extraversion at 8g/L, where low extraverts
      showed a higher proportion of responses preferring the sweeter sample. Most
      significant differences were found only under the highest tasted concentration
      (32g/L). Females and novices preferred sweeter samples (p<0.05) when compared
      with the response of males and experienced consumers, respectively.

PMID- 29579939
TI  - Maltodextrin: A consummate carrier for spray-drying of xylooligosaccharides.
AB  - The aim of this study was to evaluate the influence of spray-drying on the powder
      qualities and microstructures of prebiotic xylooligosaccharides (XOS). The
      relationships between glass transition temperature (Tg) and XOS retention,
      moisture content, drying yield as well as specific surface area under different
      inlet air temperatures and maltodextrin concentrations were investigated.
      Antioxidant activity retention, hygroscopicity, color attributes, X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FT-IR) of the spray-dried XOS product were also assessed.
      The results indicated that an increase in inlet air temperature decreased the
      moisture content, hence the Tg value was increased. Higher maltodextrin
      concentration increased the Tg value, and was attributed to the molecular weight
      increase. The wall deposition was a tendency to occur when the temperature beyond
      the Tg, reduced the drying yield. Higher temperature and wall deposition promoted
      the decomposition of XOS into monosaccharide. The crust formation rate of
      droplets and stickiness of microparticles were affected by Tg, and hence,
      influenced the specific surface area. The antioxidant activity retention of XOS
      exhibited a concentration-dependent behavior. The hygroscopicity of the
      microparticles could be reduced by both of the low inlet air temperature and high
      maltodextrin concentration. According to the results of color attributes, XRD and
      SEM, the particles were colorless and amorphous, and tended to become more
      spherical and scattered with the addition of maltodextrin. The FT-IR analysis
      confirmed that no chemical reaction occurred between XOS and agent, which
      indicated that maltodextrin is a promising carrier for producing bioactive XOS
      powder.

PMID- 29579940
TI  - Impact of temperature, nutrients, pH and cold storage on the germination, growth
      and resistance of Bacillus cereus spores in egg white.
AB  - B. cereus spores are a concern to the food industry, especially to the producers
      of heat sensitive food products like egg white or precooked and stored food such
      as fried rice. This study investigated the impact of nutrients, temperature (4,
      8, 15 and 25  degrees C), pH (4, 5, 7 and 9), and cold storage on the
      germination, growth and resistance of B. cereus spores. In egg white held at 4 
      degrees C for 12 days spore germination was not apparent, however the addition of
      egg yolk (5%) resulted in a 2 Log colony forming units (CFU)/mL increase in
      vegetative cells (p < .05). Adding l-alanine (0.9 mg/mL) to egg white did not
      induce germination unless the spores were simultaneously heat activated at 70 
      degrees C for 30 min. On incubation at 15 or 25  degrees C in egg white, spore
      germination increased by 3.0 Log and 3.7 Log CFU/mL on day 12. The presence of 5%
      yolk further enhanced germination and subsequent sporulation during storage at 15
      and 25  degrees C. Acidification (pH 4) of 10% egg white solution prevented
      germination at 4, 8, 15 and 25  degrees C. Spores held at 4  degrees C for 6 days
      in phosphate buffer (50 mM, pH 4) had visible deformations on their surface
      (scanning electron microscopy) and a significant reduction in D88, and D92 values
      of 13.9 and 8.2 min respectively. A better understanding of how spores sense and
      respond to changing environmental conditions will help in the development of
      processing strategies, involving multiple hurdles to ensure the prevention of
      germination and subsequent toxin production.

PMID- 29579942
TI  - A novel antioxidative peptide derived from chicken blood corpuscle hydrolysate.
AB  - Chicken blood contains copious amounts of edible protein, which is currently
      underutilized. In this study, chicken blood corpuscle was hydrolyzed using two
      proteases (papain and flavourzyme) and its hydrolysis conditions were optimized
      by means of response surface methodology (RSM). The optimal conditions based on
      obtaining a hydrolysate with maximum antioxidant activity were E/S 2.0%,
      temperature 50 degrees C, and time 6.0h. Under the above conditions, the DPPH
      (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, superoxide anion
      scavenging activity and reducing power of papain and flavourzyme hydrolysate
      (PFH) were 94.99+/-0.31%, 57.39+/-2.82%, and 1.83+/-0.06, respectively.
      Additionally, PFH showed not only a stable DPPH scavenging activity in the pH
      ranges of 1 to 7, but also a good tolerance to magnesium (Mg2+), potassium (K+)
      and calcium (Ca2+). We also found that PFH retained at least 95% of antioxidant
      capacity under simulated gastrointestinal digestion. Subsequently, PFH was
      purified sequentially by ultrafiltration, anion exchange chromatography, gel
      filtration chromatography, and high-performance liquid chromatography (HPLC).
      Finally, the sequence of the peptide with the highest antioxidant activity was
      identified to be AEDKKLIQ (943.5Da) using LC-ESI-MS/MS. Further, this peptide
      showed free radicals scavenging ability and reducing power as well as that of GSH
      (P>0.05), further evidencing its potential used as an antioxidative ingredient.

PMID- 29579941
TI  - Effect of endogenous proteins and lipids on starch digestibility in rice flour.
AB  - The composition and structure of the food matrix can have a major impact on the
      digestion. The aim of this work was to investigate the effects of endogenous
      proteins and lipids on starch digestibility in rice flour, with an emphasis on
      establishing the underlying physicochemical mechanisms involved. Native long
      grain indica rice flour and rice flour with the lipids and/or proteins removed
      were subjected to a simulated digestion in vitro. A significant increase in
      starch digestibility was observed after removal of proteins, lipids, or both. The
      starch digestibility of the rice flour without lipids was slightly lower than
      that without proteins, even though the proteins content was about 10-fold higher
      than the lipids content. Microstructural analysis suggested that the proteins and
      lipids were normally attached to the surfaces of the starch granules in the
      native rice flour, thus inhibiting their contact with digestive enzymes.
      Moreover, the proteins and lipids restricted the swelling of the starch granules,
      which may have decreased their digestion by reducing their surface areas. In
      addition, amylose-lipid complex was detected in the rice flour, which is also
      known to slow down starch digestion. These results have important implications
      for the design of foods with improved nutritional profiles.

PMID- 29579943
TI  - Moisture adsorption properties and shelf-life estimation of dried and pulverised
      edible house cricket Acheta domesticus (L.) and black soldier fly larvae Hermetia
      illucens (L.).
AB  - Edible insects are part of the diets of a significant proportion of rural
      populations in the tropics especially Africa and Asia, and their use as source of
      key nutrients for better nutrition is re-emerging. Indigenously, elemental
      methods are used to process the insects before they are consumed or sold in
      retail outlets. In recent years, better knowledge of processing, packaging and
      storage has become necessary because of commercialisation needs. A common
      processing approach involves drying after a brief heat-treatment step, and then
      milling into a powdered product which is sold to manufacturers or consumers as
      ingredient for processing final products. The hydration properties of dried
      powders of edible house cricket and black soldier fly larvae (BSFL) were studied
      with the aim of predicting shelf-life stability under typical packaging and
      storage temperatures experienced in the tropics. Moisture adsorption isotherms
      were determined gravimetrically at 25, 30 and 35  degrees C, over 0.11-0.97 water
      activity (aW) range, and the data fitted to various models. Sorption isotherms
      were of type II according to Brunauer classification indicating monolayer
      multilayer sorption behaviour. Cricket powder exhibited higher hydration
      capacity, and aW of this product was less sensitive to temperature variation as
      compared to BSFL powder. In the two products, water exhibited transitions from
      bound- to free- state at ~5 g/100 g moisture content. Based on Heiss-Eichner
      model, a shelf-life of 7 months at 25  degrees C can be achieved if the cricket
      and BSFL powders are dried to ca. 5 g/100 g moisture content and packaged in 80
      MUm thick polyethylene films. At 35  degrees C the shelf-life of the cricket
      product is shortened three- to four-fold whereas the BSFL powder is unable to
      store.

PMID- 29579944
TI  - Characterization of microbial community structure and metabolic potential using
      Illumina MiSeq platform during the black garlic processing.
AB  - Black garlic is a distinctive garlic deep-processed product made from fresh
      garlic at high temperature and controlled humidity. To explore microbial
      community structure, diversity and metabolic potential during the 12days of the
      black garlic processing, Illumina MiSeq sequencing technology was performed to
      sequence the 16S rRNA V3-V4 hypervariable region of bacteria. A total of 677,917
      high quality reads were yielded with an average read length of 416bp. Operational
      taxonomic units (OTU) clustering analysis showed that the number of species OTUs
      ranged from 148 to 1974, with alpha diversity increasing remarkably, indicating
      the high microbial community abundance and diversity. Taxonomic analysis
      indicated that bacterial community was classified into 45 phyla and 1125 distinct
      genera, and the microbiome of black garlic samples based on phylogenetic analysis
      was dominated by distinct populations of four genera: Thermus, Corynebacterium,
      Streptococcus and Brevundimonas. The metabolic pathways were predicted for 16S
      rRNA marker gene sequences based on Kyoto Encyclopedia of Genes and Genomes
      (KEGG), indicating that amino acid metabolism, carbohydrate metabolism and
      membrane transport were important for the black garlic fermentation process.
      Overall, the study was the first to reveal microbial community structure and
      speculate the composition of functional genes in black garlic samples. The
      results contributed to further analysis of the interaction between microbial
      community and black garlic components at different stages, which was of great
      significance to study the formation mechanism and quality improvement of black
      garlic in the future.

PMID- 29579945
TI  - Formulating orange oil-in-water beverage emulsions for effective delivery of
      bioactives: Improvements in chemical stability, antioxidant activity and
      gastrointestinal fate of lycopene using carrier oils.
AB  - The influence of carrier oil type on the chemical stability, antioxidant
      properties and bioaccessibility of lycopene in orange oil-in-water beverage
      emulsions was investigated. The emulsions were formulated with orange oil (A),
      which was partially (50%) replaced with tributyrin (B) or corn oil (C) because of
      their distinctively different fatty acid composition. The addition of corn oil
      enhanced the physical stability of the beverage during chilled storage by
      inhibiting Ostwald ripening. The formation of oxidation products was
      insignificant after storage for 28 days at 4  degrees C, regardless the type of
      added oil. Lycopene was more susceptible to chemical degradation in the presence
      of unsaturated, long chain triglycerides and the retention followed the order: A
      (87.94%), B (64.41%) and C (57.39%). Interestingly, bioaccessibility of lycopene
      was significantly lower for emulsions formulated with 50% corn oil as opposed to
      100% orange oil as indicated by the simulated in vitro gastric digestion model.

PMID- 29579946
TI  - Comparative study on the composition of free amino acids and derivatives in the
      two botanical origins of an edible Chinese herb "Xiebai", i.e., Allium chinense
      G. Don and Allium macrostemon Bunge species.
AB  - Xiebai is an edible Chinese herb with various health and therapeutic benefits. To
      evaluate its nutritional and health values, the free amino acids and derivatives
      of its two botanical origins (i.e., Allium chinense G. Don and Allium macrostemon
      Bunge) were isolated using a solvent extraction method and analyzed using
      automatic amino acid analysis and ultra-performance liquid chromatography
      quadrupole-time of flight (UPLC-Q-TOF) mass spectrometry. Our data show that both
      plants contain abundant free amino acids, and the amount of total free amino
      acids in A. chinense G. Don is higher than that in A. macrostemon Bunge. The free
      amino acid compositions in the two plants are qualitatively similar, including
      nineteen proteinogenic and four non-proteinogenic amino acids. The identified
      proteinogenic amino acids include eight essential amino acids and five semi
      essential amino acids. The sum of essential and semi-essential amino acids
      accounts for 64.9% and 69.7% of the total free amino acids of the two plants,
      respectively. The principal amino acids of both plants, from highest
      concentration to lowest concentration, are arginine, glutamine, glutamic acid,
      asparagine and serine. A. chinense G. Don is also rich in citrulline and lysine.
      In addition, two amino acid derivatives were identified from the two plants,
      i.e., the proline analog N-methyl-proline and the dipeptide H-Glu-Tyr-OH. For the
      first time, the presence of N-methyl-proline in the plants of the Allium genus
      and the presence of H-Glu-Tyr-OH in unprocessed food sources are reported. The
      influences of the identified substances on the flavor, nutrition and health
      values of Xiebai are discussed.

PMID- 29579947
TI  - Sensory description of marine oils through development of a sensory wheel and
      vocabulary.
AB  - The Omega-3 industry lacks a defined methodology and a vocabulary for evaluating
      the sensory quality of marine oils. This study was conducted to identify the
      sensory descriptors of marine oils and organize them in a sensory wheel for use
      as a tool in quality assessment. Samples of marine oils were collected from six
      of the largest producers of omega-3 products in Norway. The oils were selected to
      cover as much variation in sensory characteristics as possible, i.e. oils with
      different fatty acid content originating from different species. Oils were
      evaluated by six industry expert panels and one trained sensory panel to build up
      a vocabulary through a series of language sessions. A total of 184 aroma (odor by
      nose), flavor, taste and mouthfeel descriptors were generated. A sensory wheel
      based on 60 selected descriptors grouped together in 21 defined categories was
      created to form a graphical presentation of the sensory vocabulary. A selection
      of the oil samples was also evaluated by a trained sensory panel using
      descriptive analysis. Chemical analysis showed a positive correlation between
      primary and secondary oxidation products and sensory properties such as
      rancidity, chemical flavor and process flavor and a negative correlation between
      primary oxidation products and acidic. This research is a first step towards the
      broader objective of standardizing the sensory terminology related to marine
      oils.

PMID- 29579948
TI  - Multiple protective effect of peptides released from Olea europaea and Prunus
      persica seeds against oxidative damage and cancer cell proliferation.
AB  - The long exposition to reactive species results in oxidative stress which has
      been related with the development of cancer and other serious diseases. Olea
      europaea and Prunus persica seeds present a high protein content and preliminary
      results demonstrated their high potency to obtain bioactive peptides. The
      protective effect against oxidative damage exerted by peptides released from Olea
      europaea and Prunus persica seeds has been evaluated in this work. Seed
      hydrolysates showed protection against oxidation through four different
      mechanisms: inhibition of the formation of hydroxyl radicals, scavenging of free
      radicals, reduction of oxidizing compounds, and inhibition of lipid peroxidation.
      Moreover, seed hydrolysates also reduced the oxidative stress induced by an
      oxidizing agent on human cancer cells. Despite protection evaluated by individual
      mechanisms seemed to be significantly affected by the seed genotype, overall
      protection of seed hydrolysates was not so different. Seeds hydrolysates were not
      cytotoxic on normal cells but they demonstrated antiproliferative effect on human
      cancer cells (HeLa, PC-3, and HT-29). Peptides in all seed hydrolysates were
      sequenced by RP-HPLC-ESI-Q-TOF. Eighteen common peptides were observed among
      olive seed hydrolysates while a wider variability was observed among Prunus seed
      hydrolysates.

PMID- 29579950
TI  - Hydrolysis and transepithelial transport of two corn gluten derived bioactive
      peptides in human Caco-2 cell monolayers.
AB  - The objective of this paper was to investigate the transepithelial transport of
      two novel corn gluten-derived antioxidant peptides, YFCLT and GLLLPH, using Caco
      2 cell monolayers. Results showed that both of YFCLT and GLLLPH could transport
      in intact form across Caco-2 cell monolayers with apparent permeability
      coefficient (Papp) values of (1.10+/-0.16)*10-7cm/s and (1.98+/-0.23)*10-7cm/s,
      respectively. However, it was found that the two peptides were susceptible and
      easily hydrolyzed by brush border membrane peptidases. In the presence of
      diprotin A, an inhibitor of dipeptidyl peptidase IV (DPPIV), the hydrolysis of
      YFCLT and GLLLPH decreased and their permeabilities increased significantly
      compared to control group (P<0.05). The results of transport routes revealed that
      Gly-Sar, a peptide transporter 1 (PepT1) substrate, had little effects on the
      transepithelial permeability (P>0.05), suggesting that the transport of YFCLT and
      GLLLPH across Caco-2 cell monolayers was not mediated by PepT1. However, it was
      found that cytochalasin d, a tight junctions (TJs) disruptor, increased the
      permeability significantly (P<0.05). While wortmannin, a transcytosis inhibitor,
      and sodium azide, an ATP synthesis inhibitor, both decreased the permeability
      significantly (P<0.05). It indicated that the TJs-mediated paracellular pathway
      and energy-dependent transcytosis were involved in the transport of YFCLT and
      GLLLPH across Caco-2 cell monolayers.

PMID- 29579949
TI  - Microbiological criteria and ecology of commercially available processed cheeses
      according to the product specification and physicochemical characteristics.
AB  - Although global cheese manufacturers release a variety of products onto the
      market, research on the microbiological quality and safety of cheese has focused
      mainly on conventional cheeses made from milk. Here, this study aimed to
      investigate commercially processed cheese products produced by mixing
      conventional cheeses after melting. Two approaches were used: a summary and
      comparison of legal definitions and standards/regulations regarding the
      microbiological criteria used by major cheese traders in the global market
      (Australia/New Zealand, China, European Union, Japan, Mexico, Republic of Korea,
      and the United States) and a comprehensive microbiological analysis of commercial
      products (n = 800), along with an assessment of salinity, pH, water activity, and
      heating conditions. The results of the literature search showed that major
      importing countries (China, Japan, Mexico, and the Republic of Korea) have
      stricter microbiological criteria for commercially available cheese products than
      major exporters (Australia/New Zealand, EU, and the USA). The former set limits
      with respect to the number of total coliforms in the product. Microbiological
      analyses were designed according to global standards and recommendations. No test
      sample contained detectable levels of Clostridium perfringens, enterohemorrhagic
      Escherichia coli, Listeria monocytogenes, Salmonella, or Staphylococcus aureus.
      In addition, no coliform bacteria (including E. coli) were detected. Overall,
      79.9% of the samples contained detectable aerobic plate counts (1.0-7.8 log
      CFU/g); these levels varied significantly according to product type (grated
      cheese > chunks; cream cheese > portions or sliced) (p < .05). There was no
      significant association between microbe levels and salinity, water activity, pH,
      and heating conditions. The results can be used to develop a comprehensive
      database about commercially processed cheese products available in the global
      market and, as such, may be helpful for both national authorities and cheese
      manufacturers when considering novel strategic management plans for
      microbiological quality and safety.

PMID- 29579951
TI  - Stability of functional compounds and antioxidant activity of fresh and
      pasteurized orange passion fruit (Passiflora caerulea) during cold storage.
AB  - This research aimed to evaluate differences in the stability of physicochemical
      and color parameters, phenolic compounds, flavonoids, carotenoids and antioxidant
      capacity in fresh and pasteurized juice of orange passion fruit, respectively
      cold stored (8  degrees C) during 0-4 or during 0-15 days. The results showed
      that in the physicochemical analysis, no significant differences were observed
      comparing pasteurized and fresh juice during storage. The pasteurized juice
      showed higher concentrations of color parameters, phenolic compounds (15% more of
      retention for days 0 and 4), epigallocatechin gallate (40% in day 0 and 27% in
      day 4), lycopene (142% for day 0 and 39% for day 4), total carotenoids (114% in
      day 0 and 8% in day 4) and antioxidant capacity (12% in day 0 and 7% in day 4).;
      already fresh juice retained more values of quercetin (79% in day 0 and 245% in
      day 4), alpha-carotene (57% in day 4), beta-carotene and provitamin A (80% of
      retention in day 4). Therefore, the pasteurization processing was positive in
      orange passion fruit juice and improved the accessibility of most bioactive
      compounds.

PMID- 29579952
TI  - High pressure homogenization combined with pH shift treatment: A process to
      produce physically and oxidatively stable hemp milk.
AB  - Hemp milk, an emerging beverage with high nutritional value and low
      allergenicity, is an attractive alternative to dairy, soy, and nut milks. To
      obtain a non-thermally processed, physically and oxidatively stable hemp milk,
      high pressure homogenization (HPH) combined with pH shift treatment was
      investigated. For hemp milk (4% protein, 5% fat) without pH shift, increasing the
      homogenization pressure (up to 60 MPa) resulted in a more uniform distribution of
      emulsion droplets (2.2-2.7 MUm). When pH shift was applied prior to HPH, large
      clusters and aggregates of oil droplets (3.5-8.2 MUm) were formed. Interestingly,
      hemp milk with such interactive structures was remarkably stable, showing
      negligible phase separation within 3-day storage at 4  degrees C. Moreover, hemp
      milk made by combined pH shift and HPH exhibited delayed hydroperoxides
      (expressed as peroxide value, PV) and malondialdehyde (expressed as
      thiobarbituric acid-reactive substances, TBARS) production, suggesting the
      resistance of such emulsion cluster structures to radicals. On the other hand, a
      significant reduction of microbial population was observed in hemp milk prepared
      by pH shift combined with HPH. The results indicate that the pH shift + HPH
      combination treatment may potentially be employed for the production of non
      thermally processed hemp milk.

PMID- 29579953
TI  - Effects of the gastric juice injection pattern and contraction frequency on the
      digestibility of casein powder suspensions in an in vitro dynamic rat stomach
      made with a 3D printed model.
AB  - Previously, we have prepared a version of the dynamic in vitro rat stomach system
      (DIVRS-II or Biomimic Rat II). It was constructed and tested by showing similar
      digestive behaviors with those occurred in vivo. In the present work, a 3D
      printed plastic mold was employed to create highly repeatable silicone rat
      stomach model. It has been seen to have shortened the time to handcraft a model
      like that used in DIVRS-II. The maximum mechanical force of the current stomach
      model generated by rolling extrusion is found to be more stable probably due to
      the more uniform wall thickness of the new model. Then the effects of the
      simulated gastric secretion patterns and contraction frequency of the system on
      the in vitro digestibility of casein powder suspensions were investigated. The
      results have shown that the location of the gastric secretion injection has an
      impact on experimental digestibility. The position of rolling-extrusion area,
      established at the central part of glandular portion (stomach B), displayed the
      highest digestibility compared to that at the other locations. Furthermore, the
      extent of digestion was positively correlated with the contraction frequency of
      the model stomach system, with the maximum frequency of 12cpm giving the highest
      digestibility. This highest digestibility is almost the same as the average value
      found in vivo. The better digestive performance produced by optimizing the
      gastric secretion pattern and contraction frequency may be both resulted from the
      improved mixing efficiency of the food matrix with digestive juice. This study
      shows that it is possible to achieve what in vivo in a simulated digestion
      device, which may be used for future food and nutrition studies in vitro.

PMID- 29579954
TI  - Effect of household cooking techniques on the microbiological load and the
      nutritional quality of mealworms (Tenebrio molitor L. 1758).
AB  - Mealworms are new food products in Europe, but consumers do not know how to cook
      them. Although cooking could increase the safety, acceptability, palatability,
      and digestibility of insects, the heating process could have deleterious effects
      on protein and lipid quality. Therefore, this study characterized the effects of
      different household cooking methods (boiling, pan-frying, vacuum cooking, and
      oven cooking) on the microbial load and nutritive value of mealworms, with a
      focus on protein digestibility and fatty acid composition. Boiling and cooking
      under vacuum were the most efficient techniques to reduce microbial load while
      maintaining the high levels of protein and polyunsaturated fatty acids of
      mealworms. Cooking method-related changes were very low on macronutrients content
      except for pan-fried mealworms which exhibited the highest lipid content. Cooking
      slightly changed fatty acid composition of mealworms by principally decreasing
      their level of saturated fatty acids but also increased the in vitro crude
      protein digestibility of mealworms.

PMID- 29579955
TI  - Improving microbiological safety and quality characteristics of wheat and barley
      by high voltage atmospheric cold plasma closed processing.
AB  - Contamination of cereal grains as a key global food resource with insects or
      microorganisms is a persistent concern for the grain industry due to irreversible
      damage to quality and safety characteristics and economic losses. Atmospheric
      cold plasma presents an alternative to conventional grain decontamination methods
      owing to the high antimicrobial potential of reactive species generated during
      the treatment, but effects against product specific microflora are required to
      understand how to optimally develop this approach for grains. This work
      investigated the influence of ACP processing parameters for both cereal grain
      decontamination and grain quality as important criteria for grain or seed use. A
      high voltage (HV) (80 kV) dielectric barrier discharge (DBD) closed system was
      used to assess the potential for control of native microflora and pathogenic
      bacterial and fungal challenge microorganisms, in tandem with effects on grain
      functional properties. Response surface modelling of experimental data probed the
      key factors in relation to microbial control and seed germination promotion. The
      maximal reductions of barley background microbiota were 2.4 and 2.1 log10 CFU/g
      and of wheat - 1.5 and 2.5 log10 CFU/g for bacteria and fungi, respectively,
      which required direct treatment for 20 min followed by a 24 h sealed post
      treatment retention time. In the case of challenge organisms inoculated on barley
      grains, the highest resistance was observed for Bacillus atrophaeus endospores,
      which, regardless of retention time, were maximally reduced by 2.4 log10 CFU/g
      after 20 min of direct treatment. The efficacy of the plasma treatment against
      selected microorganisms decreased in the following order: E. coli > P. verrucosum
      (spores) > B. atrophaeus (vegetative cells) > B. atrophaeus (endospores). The
      challenge microorganisms were more susceptible to ACP treatment than naturally
      present background microbiota. No major effect of short term plasma treatment on
      the retention of quality parameters was observed. Germination percentage measured
      after 7 days cultivation was similar for samples treated for up to 5 min, but
      this was decreased after 20 min of direct treatment. Overall, ACP proved
      effective for cereal grain decontamination, but it is noted that the diverse
      native micro-flora may pose greater resistance to the closed, surface
      decontamination approach than the individual fungal or bacterial challenges,
      which warrants investigation of grain microbiome responses to ACP.

PMID- 29579956
TI  - Mechanistic insight into softening of Canadian wonder common beans (Phaseolus
      vulgaris) during cooking.
AB  - The relative contributions of cotyledons and seed coats towards hardening of
      common beans (Phaseolus vulgaris) were investigated and the rate-limiting process
      which controls bean softening during cooking was determined. Fresh or aged whole
      beans and cotyledons were soaked and cooked in demineralised water or 0.1 M
      NaHCO3 solution, and texture evolution, microstructure changes and thermal
      properties were studied. Fresh and aged whole beans cooked in demineralised water
      had significantly different softening rate constants and so did fresh and aged
      cotyledons. The comparable softening rate constants of aged whole beans and
      cotyledons indicated an insignificant role of the seed coat in hardening during
      storage. All samples cooked faster in 0.1 M NaHCO3 solution. Disintegration of
      cooked tissues followed by microscopic examination revealed a transition from
      cell breakage through a phase of cell breakage and separation to complete cell
      separation with increased cooking time wherefore texture decayed. Therefore,
      progressive solubilization of pectin in the middle lamella greatly promoted
      texture decay. While residual birefringence even after substantial cooking time
      suggested some molecular order of the starch, calorimetric analyses revealed
      complete starch gelatinisation before complete cell separation occurred. This
      implies an insignificant role of starch in texture decay during cooking but its
      hindered uncoiling into a viscous gel after gelatinisation due to the restricting
      cell wall could promote its retrogradation. Therefore, we suggest that the rate
      determining process in bean softening relates to cell wall/middle lamella changes
      influencing pectin solubilization.

PMID- 29579957
TI  - The role of product information on consumer sensory evaluation, expectations,
      experiences and emotions of cricket-flour-containing buns.
AB  - Studies suggest that consumer' acceptance of edible insects can be enhanced by
      processing and blending them with familiar food products. This is however,
      expected to result in changes in some sensory attributes. In this study, we
      investigated how consumers evaluate the appropriateness of sensory attributes of
      a common bakery product (buns) that was blended with cricket-flour i.e., cricket
      flour-containing (CFC) buns. We also tested whether provision of information can
      modulate the sensory evaluations, personal involvement and emotions. The study is
      based on a field experiment involving 432 participants drawn from rural
      communities in Kenya. Participants were randomly assigned to 3 information
      treatment groups: i) Control group - received only general information, ii)
      Treatment 1 - received general information and information about the benefits
      (i.e., positive attributes), iii) Treatment 2 - received general information and
      information about the potential drawbacks (i.e., negative attributes).
      Participants evaluated the CFC buns before and after tasting using Just-About
      Right (JAR) scale. Results indicate that providing product information affected
      sensory evaluation of the product's sensory attributes. They also indicate that
      actual tasting of the CFC buns improved the convergence of sensory evaluation of
      the attributes towards the ideal level. Results further show that CFC buns
      elicited more positive feelings with little differences in the emotional profiles
      between the information treatments, which suggests general interest in the buns.
      These results provide useful insights on how to enhance consumer acceptance of
      insect-based foods. We discuss the implications of the findings.

PMID- 29579958
TI  - Simultaneous HPLC determination of flavonoids and phenolic acids profile in Pera
      Rio orange juice.
AB  - The aim of this study was to develop and validate an HPLC-DAD method to evaluate
      the phenolic compounds profile of organic and conventional Pera-Rio orange juice.
      The proposed method was validated for 10 flavonoids and 6 phenolic acids. A wide
      linear range (0.01-223.4MUg.g-1), good accuracy (79.5-129.2%) and precision
      (CV<=3.8%), low limits of detection (1-22ng.g-1) and quantification (0.7-7.4MUg),
      and overall ruggedness were attained. Good recovery was achieved for all phenolic
      compounds after extraction and cleanup. The method was applied to organic and
      conventional Pera-Rio orange juices from beginning, middle and end of the 2016
      harvest. Flavones rutin, nobiletin and tangeretin, and flavanones hesperidin,
      narirutin and eriocitrin were identified and quantified in all organic and
      conventional juices. Identity was confirmed by mass spectrometry. Nineteen non
      identified phenolic compounds were quantified based on DAD spectra characteristic
      of the chemical class: 7 cinnamic acid derivatives, 6 flavanones and 6 flavones.
      The phenolic compounds profile of Pera-Rio orange juices changed during the
      harvest; levels increased in organic orange juices, and decreased or were about
      the same in conventional orange juices. Phenolic compounds levels were higher in
      organic (0.5-1143.7mg.100g-1) than in conventional orange juices (0.5
      689.7mg.100g-1). PCA differentiated organic from conventional FS and NFC juices,
      and conventional FCOJ from conventional FS and NFC juices, thus differentiating
      cultivation and processing.

PMID- 29579959
TI  - Formulation and characterization of water-in-oil nanoemulsions loaded with acai
      berry anthocyanins: Insights of degradation kinetics and stability evaluation of
      anthocyanins and nanoemulsions.
AB  - Acai berry is the fruit of an Amazonian palm tree and rich in anthocyanins
      (ACNs). Scientific studies have proven the health benefits of acai berry and
      declared this fruit as "super fruit". ACNs have high antioxidant activities, but
      they are unstable and can easily deteriorate during food processing. In order to
      protect ACNs and increase their applicability, food-grade water-in-oil (W/O)
      emulsions were successfully formulated with different concentrations of acai
      berry extracts (AEs). The formulated W/O nanoemulsions were relatively stable,
      with no phase separation after 30 days of storage. The average droplet size
      varied between 146.8 and 814.8 nm, with higher values corresponding to samples
      without AEs. All W/O nanoemulsion samples exhibited antioxidant activity and high
      retention rates of polyphenols after 30 days of storage. ACN retention followed
      first-order kinetics, with high protection of ACNs observed in emulsified
      samples. 2% AE encapsulated in a 30 wt% W/O nanoemulsion had an estimated half
      life of 385 days. The results indicate that stable nanoemulsion systems with high
      ACN protection can be produced with possible applications in the food and
      pharmaceutical industries.

PMID- 29579960
TI  - Ultrasonic-assisted extraction combined with sample preparation and analysis
      using LC-ESI-MS/MS allowed the identification of 24 new phenolic compounds in
      pecan nut shell [Carya illinoinensis (Wangenh) C. Koch] extracts.
AB  - Ultrasonic-assisted extraction combined with statistical tools (factorial design,
      response surface methodology and kinetics) were used to evaluate the effects of
      the experimental conditions of temperature, solid-to-solvent ratio, ethanol
      concentration and time for the extraction of the total phenolic content from
      pecan nut shells. The optimal conditions for the aqueous and hydroalcoholic
      extract (with 20% v/v of ethanol) were 60 and 80  degrees C; solid to solvent
      ratio of 30 mL.g-1 (for both) and extraction time of 35 and 25 min, respectively.
      Using these optimize extraction conditions, 426 and 582 mg GAE.g-1 of phenolic
      compounds, from the aqueous and hydroalcoholic phases respectively, were
      obtained. In addition, the analysis of the phenolic compounds using the LC-ESI
      MS/MS system allowed the identification of 29 phenolic compounds, 24 of which had
      not been reported in literature for this raw material yet.

PMID- 29579961
TI  - Evaluation of the neuroprotective and antidiabetic potential of phenol-rich
      extracts from virgin olive oils by in vitro assays.
AB  - In this work, phenol-rich extracts from 'Cornicabra' and 'Picual' virgin-olive
      oils (EVOOs) were examined, for the first time, to establish their capacity to
      inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase
      (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (LOX)), major depressive
      disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: hMAO-A and hMAO
      B respectively), and diabetes mellitus (DM) (alpha-glucosidase and alpha
      amylase). 'Cornicabra' displayed the best inhibitory activity against all
      enzymes, when compared to 'Picual': BuChE (IC50 = 156 +/- 4 and 308 +/- 33 mg mL
      1), LOX (IC50 = 26 +/- 0.5 and 37 +/- 3 mg mL-1), hMAO-A (IC50 = 20 +/- 2 and 37
      +/- 0.2 mg mL-1), hMAO-B (IC50 = 131 +/- 7 and 215 +/- 13 mg mL-1) and alpha
      glucosidase (IC50 = 154 +/- 17 and 251 +/- 31 mg mL-1), respectively. The
      behaviour observed can be associated with the higher content of secoiridoids,
      lignans and phenolic acids in 'Cornicabra' EVOO.

PMID- 29579962
TI  - The effect of prefermentative addition of gallic acid and ellagic acid on the red
      wine color, copigmentation and phenolic profiles during wine aging.
AB  - : Though non-anthocyanin phenolics normally do not have red color, they affect
      the red color expression in the copigmentation of red wines. In this study, the
      influence of prefermentative addition of 300mg/L gallic acid and ellagic acid, as
      cofactors, on aging dry red wines had been systematically evaluated at the
      industrial scales from the perspectives of color, phenolic profiles and
      copigmentation effects of anthocyanins. Red wines made with these two compounds
      exhibited better color properties than the control, having better CIELAB
      chromatic parameters. Additionally, significantly higher levels of detectable
      anthocyanins and copigmented anthocyanin ratio had been observed. Wines with
      ellagic acid showed better chromatic properties and phenolic profiles than wines
      with gallic acid, as shown in previous theoretical results. Anti-copigmentation
      phenomenon was noticed and elucidated. These practical results confirmed that
      ellagic acid was the better cofactor, and would give more additional guidance for
      the production of high quality wine. CHEMICAL COMPOUNDS: Malvidin-3-O-glucoside
      (PubChem CID: 443,652); Petunidin-3-O-glucoside (PubChem CID: 443,651);
      Delphinidin-3-O-glucoside (PubChem CID: 443,650); Peonidin-3-O-glucoside (PubChem
      CID: 443,654); Ellagic acid (PubChem CID: 5,281,855); Gallic acid (PubChem CID:
      370); Quercetin (PubChem CID: 443,654); Caffeic acid (PubChem CID: 689,043); (+)
      catechin (PubChem CID: 9064); Vanillic acid (PubChem CID: 8468).

PMID- 29579963
TI  - On the effect of ultrasound-assisted atmospheric freeze-drying on the antioxidant
      properties of eggplant.
AB  - The low operating temperatures employed in atmospheric freeze-drying permits an
      effective drying of heat sensitive products, without any impairment of their
      quality attributes. When using power ultrasound, the drying rate can be
      increased, thus reducing the process duration. However, ultrasound can also
      affect the product quality. The aim of this study was to evaluate the effect of
      various drying process variables, namely air temperature and velocity, ultrasound
      power and sample size, on the antioxidant properties of eggplant (Solanum
      melongena L.) samples. For this reason, drying experiments were carried out at
      different drying temperatures (-5, -7.5, -10  degrees C), power ultrasound levels
      (0, 25, 50 W; 21.9 kHz) and air velocities (2, 5 m s-1) using different sample
      sizes (8.8 mm and 17.6 mm cube side). The ascorbic acid content (Jagota and Dani
      method), total phenolic content (Folin-Ciocalteau method), and the antioxidant
      capacity (FRAP method) of the dried products were considered as quality
      indicators of the dried samples. The increase in air velocity and temperature, as
      well as the sample size, significantly reduced the antioxidant potential of the
      dried samples (p-value < .05). For a given sample size, the application of
      ultrasound, at the acoustic power levels tested, did not produce significant
      effects on the antioxidant indicators considered. Temperature measurements inside
      the drying sample showed a non-negligible temperature rise when acoustic power
      was applied.

PMID- 29579964
TI  - High angiotensin-I converting enzyme (ACE) inhibitory activity of Alcalase
      digested green soybean (Glycine max) hydrolysates.
AB  - As a protein-rich, underutilized crop, green soybean could be exploited to
      produce hydrolysates containing angiotensin-I converting enzyme (ACE) inhibitory
      peptides. Defatted green soybean was hydrolyzed using four different food-grade
      proteases (Alcalase, Papain, Flavourzyme and Bromelain) and their ACE inhibitory
      activities were evaluated. The Alcalase-generated green soybean hydrolysate
      showed the highest ACE inhibitory activity (IC50: 0.14 mg/mL at 6 h hydrolysis
      time) followed by Papain (IC50: 0.20 mg/mL at 5 h hydrolysis time), Bromelain
      (IC50: 0.36 mg/mL at 6 h hydrolysis time) and Flavourzyme (IC50: 1.14 mg/mL at 6
      h hydrolysis time) hydrolysates. The Alcalase-generated hydrolysate was profiled
      based on its hydrophobicity and isoelectric point using reversed phase high
      performance liquid chromatography (RP-HPLC) and isoelectric point focusing (IEF)
      fractionators. The Alcalase-generated green soybean hydrolysate comprising of
      peptides EAQRLLF, PSLRSYLAE, PDRSIHGRQLAE, FITAFR and RGQVLS, revealed the
      highest ACE inhibitory activity of 94.19%, 99.31%, 92.92%, 101.51% and 90.40%,
      respectively, while their IC50 values were 878 MUM, 532 MUM, 1552 MUM, 1342 MUM
      and 993 MUM, respectively. It can be concluded that Alcalase-digested green
      soybean hydrolysates could be exploited as a source of peptides to be
      incorporated into functional foods with antihypertensive activity.

PMID- 29579965
TI  - Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source
      of antidiabetic peptides.
AB  - Large quantities of low-value protein rich co-products, such as salmon skin and
      trimmings, are generated annually. These co-products can be upgraded to high
      value functional ingredients. The aim of this study was to assess the
      antidiabetic potential of salmon skin gelatin and trimmings-derived protein
      hydrolysates in vitro. The gelatin hydrolysate generated with Alcalase 2.4L and
      Flavourzyme 500L exhibited significantly higher (p < 0.001) insulin and GLP-1
      secretory activity from pancreatic BRIN-BD11 and enteroendocrine GLUTag cells,
      respectively, when tested at 2.5 mg/mL compared to hydrolysates generated with
      Alcalase 2.4L or Promod 144MG. The gelatin hydrolysate generated with Alcalase
      2.4L and Flavourzyme 500L showed significantly more potent (p < 0.01) DPP-IV
      inhibitory activity than those generated with Alcalase 2.4L or Promod 144MG. No
      significant difference was observed in the insulinotropic activity mediated by
      any of the trimmings-derived hydrolysates when tested at 2.5 mg/mL. However, the
      trimmings hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L exhibited
      significantly higher DPP-IV inhibitory (p < 0.05:Alcalase 2.4L and p <
      0.01:Promod 144MG) and GLP-1 (p < 0.001, 2.5 mg/mL) secretory activity than those
      generated with Alcalase 2.4L or Promod 144MG. The salmon trimmings hydrolysate
      generated with Alcalase 2.4L and Flavourzyme 500L when subjected to simulated
      gastrointestinal digestion (SGID) was shown to retain its GLP-1 secretory and DPP
      IV inhibitory activities, in addition to improving its insulin secretory
      activity. However, the gelatin hydrolysate generated with Alcalase 2.4L and
      Flavourzyme 500L was shown to lose GLP-1 secretory activity following SGID. A
      significant increase in membrane potential (p < 0.001) and intracellular calcium
      (p < 0.001) by both co-product hydrolysates generated with Alcalase 2.4L and
      Flavourzyme 500L suggest that both hydrolysates mediate their insulinotropic
      activity through the KATP channel-dependent pathway. Additionally, by stimulating
      a significant increase in intracellular cAMP release (p < 0.05) it is likely that
      the trimmings-derived hydrolysate may also mediate insulin secretion through the
      protein kinase A pathway. The results presented herein demonstrate that salmon co
      product hydrolysates exhibit promising in vitro antidiabetic activity.

PMID- 29579966
TI  - The impact of newly produced protein and dietary fiber rich fractions of yellow
      pea (Pisum sativum L.) on the structure and mechanical properties of pasta-like
      sheets.
AB  - Two fractions from pea (Pisum sativum L.), protein isolate (PPI) and dietary
      fiber (PF), were newly produced by extraction-fractionation method and
      characterized in terms of particle size distribution and structural morphology
      using SEM. The newly produced PPI and PF fractions were processed into pasta-like
      sheets with varying protein to fiber ratios (100/0, 90/10, 80/20, 70/30 and
      50/50, respectively) using high temperature compression molding. We studied
      protein polymerization, molecular structure and protein-fiber interactions, as
      well as mechanical performance and cooking characteristics of processed PPI-PF
      blends. Bi-modal particle size distribution and chemical composition of the PPI
      and PF fractions influenced significantly the physicochemical properties of the
      pasta-like sheets. Polymerization was most pronounced for the 100 PPI, 90/10 and
      80/20 PPI-PF samples as studied by SE-HPLC, and polymerization decreased with
      addition of the PF fraction. The mechanical properties, as strength and
      extensibility, were likewise the highest for the 100 PPI and 90/10 PPI-PF blends,
      while the E-modulus was similar for all the studied blends (around 38 MPa). The
      extensibility decreased with the increasing amount of PF in the blend. The
      highest amounts of beta-sheets were found in the pasta-like sheets with high
      amounts of PPI (100, 90 and 80%), by FT-IR. An increase in PF fraction in the
      blend, resulted into the high amounts of unordered structures as observed by FT
      IR, as well as in an increase in the molecular scattering distances observed by
      SAXS. The water uptake increased and cooking loss decreased with increased
      proportions of the PF fraction, and the consistency of 10 min cooked pasta-like
      sheets were alike al dente texture. The new knowledge obtained in this study on
      the use of extraction-fractionation method to produce novel PPI and PF fractions
      for developing innovative high nutritious food can be of a great importance. The
      obtained knowledge on the pea protein and fiber processing behaviour could
      greatly contribute to a better control of functional properties of various
      temperature-processed products from yellow pea.

PMID- 29579967
TI  - Complexation of thermally-denatured soybean protein isolate with anthocyanins and
      its effect on the protein structure and in vitro digestibility.
AB  - The complexation of anthocyanin-rich black rice extracts (ARBRE) with soybean
      protein isolate (SPI) heated at 0, 70, 85, and 100  degrees C and its effect on
      protein digestibility were studied. The structural changes of SPI during its
      interaction with ARBRE in all the samples were studied by Fourier transform
      infrared, circular dichroism, and fluorescence spectroscopy. The secondary
      structure changes of SPI in all the samples after complexation with ARBRE showed
      a significant increase in alpha-helix and a significant decrease in beta-sheet
      contents. Results also showed that ARBRE quenched the SPI fluorescence (in both
      unheated and heated samples) via static quenching with a single binding site. The
      digestibility of unheated and heated SPI was improved upon complexing with ARBRE.
      The formation of the SPI-ARBRE complexes is beneficial for the application of soy
      protein-based products in foods by increasing their protein digestibility and
      nutritional quality.

PMID- 29579968
TI  - The regulation mechanisms of soluble starch and glycerol for production of
      azaphilone pigments in Monascus purpureus FAFU618 as revealed by comparative
      proteomic and transcriptional analyses.
AB  - Monascus spp. have been used for thousands of years as a traditional food
      additive in China. This mold can produce many different types of commercially
      valuable secondary metabolites of biological activity. Soluble starch and
      glycerol are the two principal carbon sources universally utilized by Monascus
      for the production of beneficial metabolites. In this study, the effects and
      regulation mechanisms of soluble starch and glycerol for M. purpureus FAFU618 on
      Monascus azaphilone pigments (MonAzPs) were investigated through ultra
      performance liquid chromatography quadrupole time of flight mass spectrometry
      (UPLC-QTOF-MS/MS), comparative proteomics and quantitative real-time reverse
      transcription polymerase chain reaction (RT-qPCR). The production of
      intracellular and extracellular pigments was significantly different between the
      soluble starch group (SSG) and glycerol group (GCG). Additionally, the components
      of intracellular pigments revealed by UPLC-QTOF-MS/MS showed that Monascin and
      Ankaflavin increased significantly in the GCG, while Rubropunctatin and
      Monascorubrin increased in the SSG. Differentially expressed proteins of mycelia
      between SSG and GCG were analyzed by two-dimensional gel electrophoresis (2-DE)
      and MALDI-TOF/TOF MS. We identified 27 proteins with statistically altered
      expression, of which 18 proteins associated with the EMP (glycolytic pathway),
      translation, energy generation, proteolysis, etc. were up-regulated, and 9
      proteins, including ribosomal proteins, heat shock proteins (HSPs) and others,
      were down-regulated in GCG. Meanwhile, the expression levels of MonAzP
      biosynthetic genes were also analyzed by RT-qPCR, and the results showed that
      mppA, mppC, mppR1 and mppR2 were down-regulated, whereas genes MpPKS5, MpFasA2,
      MpFasB2, mppB, mppD and mppE were up-regulated. Collectively, these findings
      illustrate that the regulation of MonAzPs is not only closely related to the
      expression levels of certain proteins in the polyketide synthesis pathway but
      also closely related to the concentration of primary metabolism-generated
      molecules that are used as substrates for polyketide synthesis. The present study
      provides insights into the regulation of different carbon sources on the
      metabolism of MonAzPs in M. purpureus FAFU618. These results may promote further
      development of functional foods or medicines from Monascus spp. fermented
      products.

PMID- 29579969
TI  - De-stoning technology for improving olive oil nutritional and sensory features:
      The right idea at the wrong time.
AB  - De-stoning technology has been introduced in the olive oil sector more than
      twenty years ago. It has not gained momentum because, sometimes, innovative ideas
      are not accepted since they are suggested at the wrong time or under the wrong
      circumstances. Virgin olive oil (VOO) is one of the most popular functional
      foods, mainly due to its antioxidant properties. These features, as well as other
      nutritional characteristics are generally enhanced by the de-stoning process.
      However, despite the improvement of the nutritional value, in the past the de
      stoned oil didn't achieve marketing success mainly in relation to technological
      limitations (i.e. low oil yield). Only in recent years healthy properties became
      an element able to influence consumers' behavior, overcoming the limit of low oil
      yields and attracting the attention of olive oil producers. An analysis of the
      advantages, in terms of product quality and process sustainability, is given in
      this review. Here, for the first time, the fragmented results reported in
      literature are critically analyzed underlining the contradictions reported by
      different authors showing the main reasons for the unlucky fate of this
      technology in the industrial sector. In the final section the challenges, that
      future research must focus on, are presented, including emerging technologies in
      VOO processing. Literature data, for the first time discussed here exhaustively,
      show that de-stoning technology is a mechanical strategy useful to increase the
      nutritional and the sensory quality of the product. Moreover, it reduces the
      depletion of natural resources obtaining a selective crushing of the drupe by
      removing the stones from the olive paste so increasing the sustainability and
      efficiency of VOO extraction plants.

PMID- 29579970
TI  - Mimicking gluten functionality with beta-conglycinin concentrate: Evaluation in
      gluten free yeast-leavened breads.
AB  - Fractionation of soy proteins has proved to produce protein concentrates with
      viscoelastic properties. In the present study, a beta-conglycinin concentrate
      (betaCC) obtained by a pH fractionation of soy flour was tested as structuring
      agent in gluten-free yeast-leavened bread model. A lean formulation with betaCC
      and corn starch was used to produce gluten-free breads with two hydration
      conditions and three levels of protein (5%, 10% and 15%). Vital gluten was used
      to compare the functionality of betaCC protein and its performance for
      breadmaking. Breads were characterized in moisture, color, textural parameters
      and image analysis. betaCC presented lower hydration properties and higher
      emulsifying activity compared to vital gluten. Blends betaCC:starch had higher
      water binding capacity compared to vital gluten blends. The hydration conditions
      tested affected the moisture, color and cell density of breads. Breads produced
      with betaCC presented higher 2D area and height and presented higher crumb
      softness and cohesiveness, and did not present significant differences in
      springiness and resilience compared to vital gluten breads. The image analysis of
      crumbs showed higher cell density but lower porosity and mean cell areas in
      betaCC breads. Thus, betaCC proved to have potential as a structuring agent in
      gluten-free breads.

PMID- 29579971
TI  - Alterations in the morphological, sugar composition, and volatile flavor
      properties of petai (Parkia speciosa Hassk.) seed during ripening.
AB  - Petai seeds are one of the well-known strong-smelling foods of the Southeast
      Asian region that have been harvested and commercially offered in different
      ripening forms. The current study focused on alterations in the size, color,
      sugar composition, and volatile flavor properties of petai seeds in the four
      ripening stages (unripe, mid ripe, ripe, and over-ripe). The ripening process was
      mainly indicated by the increase in size and weight as seed color turned paler
      and less greenish. The total sugar content gradually increased during ripening,
      and then elevated from 1.60 g/100 g (ripe seed) to the level of 2.82 g/100 g in
      the over-ripe seed. Ripening also altered the volatile flavor composition of
      petai seed, wherein the predominant aldehydes (hexanal and acetaldehyde) were
      decreased, and the sulfuric compounds (hydrogen sulfide, methanethiol, and 1,2,4
      trithiolane) tended to increase. Additionally, gas chromatography-olfactometry
      (GC-O) analysis revealed alterations in the perceived odor strength and sensation
      of each volatile compound and demonstrated volatile flavor profiles, viz.
      detection percentages of volatile group odor strengths and descriptive odors, of
      petai seed. These results provide valuable information for monitoring alterations
      in the physical appearance, sugar composition, and aroma that represent the
      flavor quality in seasonal petai seed.

PMID- 29579972
TI  - Volatile molecular markers of VOO Thermo-oxidation: Effect of heating processes,
      macronutrients composition, and olive ripeness on the new emitted aldehydic
      compounds.
AB  - Heating operation has been applied to Chetoui extra-virgin olive oils (EVOOs)
      extracted from fruits with several ripening stages (RS). The studied samples,
      were subjected to microwave and conventional heating. Results showed that heated
      VOOs after 2.5 h and 7 min of conventional and microwave heating, respectively,
      gave rise to a drastically decrease of LOX products and allowed the detection of
      toxic new formed aldehydic volatiles (alkanal: nonanal, alkenals: (Z)-2-heptenal
      and (E)-2-decenal, and alkadienals: (E.E)-2.4-decadienal), which can be used as
      markers of VOO degradation. Their abundance in the VOO headspaces depends on
      their boiling points, the rate of their possible degradation to yield other
      compounds, on the heating processes and on the rate of macronutrients. The
      emission rate of the new synthesized volatiles during heating processes was
      mainly attributed to enzymatic oxidation of some fatty acids. Hexanal, (Z)-2
      heptenal, (E)-2-octenal, (E)-2-nonenal, (E,E) and (E,Z)-2,4-decadienal, and (E,E)
      2,4-nonadienal, derived from linoleic acid, and heptanol, octanal, nonanal,
      decanal, (E) and (Z)-2-decenal, (E)-2-undecenal, and (E,E)-2,4-nonadienal, are
      emitted after degradation of oleic acid. During thermo-oxidation, the ECN44 (LLO,
      and OLnO), and the ECN46 (OLO, and PLO + SLL) compounds decreased, whereas, the
      ECN48 (OOO, and PPO), and the ECN50 (SOO) compounds increased when temperature
      and heating time increased. The several variations of the studied biochemical
      compounds depend to the heating processes. Ripening stage of olive fruits can be
      used as a tool to monitor the emission rate of the aldehydic volatiles, but
      cannot be used for a chemometric discrimination.

PMID- 29579973
TI  - On printability, quality and nutritional properties of 3D printed cereal based
      snacks enriched with edible insects.
AB  - 3D printing technology was employed to obtain snacks with a designed cylindrical
      geometry from wheat flour dough enriched by ground larvae of Yellow mealworms
      (Tenebrio molitor) as novel source of proteins. The main microstructural
      features, overall quality, and nutritional attributes were studied as a function
      of formulation, time and temperature of baking. The addition of ground insects up
      to 20 g/100 g (d.b.) resulted in softer dough. This caused an overflow in dough
      deposition producing the increase in diameter, height and weight of snacks.
      Baking conditions did not alter the overall aspect of the snacks, but
      modification of the main dimensional and microstructure attributes were observed
      due to the better water evaporation. The optimization of baking conditions found
      that 22 min and 200  degrees C allowed obtaining a maximum desirability of 0.693.
      Baked in these conditions, the printed snacks enriched with 10 and 20% of ground
      insects significantly increased the total essential amino acid, from 32.5 (0%
      insects) to 38.2 and 41.3 g/100 g protein, respectively. The protein
      digestibility corrected amino acid score increased from 41.6 to 65.2 from 0 to
      20% insect enrichment, with lysine and methionine + cysteine being the respective
      limiting amino acid. Our results evidenced the rational promotion of insects
      based on nutritional arguments and validated the use of 3D printing as technology
      to manufacture innovative printed snacks without adverse impact on technological
      quality.

PMID- 29579974
TI  - Determination of four Alternaria alternata mycotoxins by QuEChERS approach
      coupled with liquid chromatography-tandem mass spectrometry in tomato-based and
      fruit-based products.
AB  - A liquid chromatography-tandem mass spectrometry method for the determination of
      four Alternaria toxins, i.e. alternariol, alternariol monomethyl ether, tentoxin,
      and tenuazonic acid in tomato-based and fruit-based products was developed using
      a QuEChERs approach for the extraction of the mycotoxins. To optimise the
      QuEChERs extraction, several parameters were tested: types of QuEChERs pouches,
      sample weights, quantities of added water, use of dispersive SPE as a
      purification step, types of solvent and conditions of shaking. The method showed
      good linearity (R2 > 0.997) and precision (RSD% < 10) for all analytes.
      Tenuazonic acid showed very good recovery (98.8%-108.9%) for tomato-based
      products, as well as for fruit-based products. The method was successfully
      applied to 57 samples collected from the Italian market. Tenuazonic acid was
      found in appreciable concentrations in some products. The highest value was found
      in a tomato sauce sample (814 MUg/kg).

PMID- 29579975
TI  - Analysis of volatile compounds in gluten-free bread crusts with an optimised and
      validated SPME-GC/QTOF methodology.
AB  - The aroma of bread crust, as one of the first characteristics perceived, is
      essential for bread acceptance. However, gluten-free bread crusts exhibit weak
      aroma. A SPME-GC/QTOF methodology was optimised with PCA and RSM and validated
      for the quantification of 44 volatile compounds in bread crust, extracting 0.75 g
      of crust at 60  degrees C for 51 min. LODs ranged between 3.60 and 1760 MUg Kg-1,
      all the R2 were higher than 0.99 and %RSD for precision and %Er for accuracy were
      lower than 9% and 12%, respectively. A commercial wheat bread crust was
      quantified, and furfural was the most abundant compound. Bread crusts of wheat
      starch and of japonica rice, basmati rice and teff flours were also quantified.
      Teff flour and wheat starch crusts were very suitable for improving gluten-free
      bread crust aroma, due to their similar content in 2-acetyl-1-pyrroline and 4
      hydroxy-2,5-dimethyl-3(2H)-furanone compared to wheat flour crust and also for
      their high content in pyrazines.

PMID- 29579976
TI  - In vitro lipolysis of dairy and soy based infant formula.
AB  - Hydrolysed and non-hydrolysed dairy and soy proteins with vegetable oils are
      commonly used in infant formulations. Lipid digestion of these infant formula
      emulsions was studied under an in vitro gastrointestinal condition for 60 min in
      the stomach and 120 min in the small intestine (with and without the presence of
      enzyme proteases). The distribution of oil droplets, the released free fatty
      acids, and micro-structure changes of the digesta were monitored over the
      digestion period. Oil droplet coalescence was observed during gastric phase but
      not in the intestinal phase for most of formulations. The emulsion structure and
      the oil-water interface of the oil droplets play an important part in lipolysis
      kinetics. Higher rate of lipolysis in infant formula emulsion stabilized by
      hydrolysed proteins was noted. The obtained results suggest that digestive
      proteases had a limited impact on lipolysis of infant formulations.

PMID- 29579977
TI  - Influence of time orientation on food choice: Case study with cookie labels.
AB  - Time orientation can influence health-related behaviors, including food
      consumption. The aim of the present work was to study the influence of time
      orientation on food choice, using cookie labels as case study. A choice-conjoint
      task was designed using labels differing in type of cookie (chocolate chips vs.
      granola), front-of-pack nutrition information (nutritional warnings vs. Facts Up
      Front system) and nutritional claim (no claim vs. "0% cholesterol. 0% trans
      fat"). An online study was conducted, in which 155 participants evaluated 8 pairs
      of cookie labels and selected the one they would buy if they were in the
      supermarket. Then, they were asked to complete a consideration of future
      consequences scale (CFC) adapted to eating habits, as well as a questionnaire
      about socio-demographic characteristics. Time orientation influenced
      participants' choices of cookies labels; particularly the importance attached to
      type of cookie. Participants with greater consideration of future consequences
      preferred the granola cookies, associated with health, while those who
      prioritized immediate consequences preferred chocolate chip cookies. In addition,
      nutritional warnings discouraged choice regardless of participants' time
      orientation. Results from the present work provide additional evidence of the
      influence of time preferences on food choices and suggest that strategies to
      stimulate and generate a more future-oriented perspective on eating habits could
      contribute to more healthful food choices.

PMID- 29579978
TI  - Cytotoxic, proapoptotic and antioxidative potential of flavonoids isolated from
      propolis against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines.
AB  - Isolated and structurally confirmed, eleven flavonoids from propolis were
      examined for their cytotoxicity toward human colon cancer and human breast cancer
      cells. Their effect on induction of apoptosis and their antioxidative activities
      were also evaluated. Six flavonoids induced cytotoxic effects in both cell lines.
      Luteolin had a marked effect on both cell lines, especially on HCT-116 cells
      (IC50 72h, 66.86MUM). Also, luteolin was observed to have the highest apoptotic
      potential after 72h treatment of examined cell lines (27.13% and 37.09%,
      respectively). Myricetin exhibited selective inhibition of cell growth (IC50
      114.75MUM) and induced apoptosis in MDA-MB-231 cells only. Luteolin and galangin
      exhibited prooxidative properties 24h after the treatment in HCT-116 cells, while
      myricetin induced prooxidative effects in MDA-MB-231 cells. On the other hand,
      selected flavonoids exhibited antioxidative properties 72h after the treatment,
      decreasing superoxide anion radical and nitrite levels in both cell lines.
      Cytotoxic and proapoptotic effects on colon and breast cancer cell lines and the
      influence on their redox status make tested flavonoids good candidates for
      developing new anticancer drugs.

PMID- 29579979
TI  - Cheese matrix protects the immunomodulatory surface protein SlpB of
      Propionibacterium freudenreichii during in vitro digestion.
AB  - Propionibacterium freudenreichii is a traditional Swiss-type cheeses starter and
      constitutes an emergent probiotic, exerting several beneficial effects, including
      anti-inflammatory modulation of gut inflammation. This feature relies on several
      metabolites and on surface proteins, with a prominent role of the surface protein
      SlpB. In this study, we firstly investigated the relevance to avoid SlpB
      digestive proteolysis, by comparing the effect of i) P. freudenreichii CIRM-BIA
      129, ii) its native Slps, or iii) peptides resulting from Slps digestive
      proteolysis, with respect to modulation of HT-29 cells response to a
      lipopolysaccharide (LPS) challenge. The anti-inflammatory effect exerted by P.
      freudenreichii CIRM-BIA 129 and by its native surface proteins (Slps) on HT-29
      cells was abolished by digestive proteolysis. This result confirmed the
      importance to protect immunomodulatory surface proteins from digestive
      proteolysis in order to allow gut immune system modulation. Thus, we examined the
      effect of dairy matrices on P. freudenreichii viability and on SlpB integrity
      during digestion. In comparison with liquid matrices, the cheese matrix provided
      an enhanced tolerance towards digestive stresses and protection of SlpB towards
      proteolysis, during two in vitro digestion models: static and dynamic. Taken
      together, these results show that cheese is an adequate delivery vehicle for P.
      freudenreichii immunomodulatory proteins. This opens perspectives for the
      development of fermented dairy functional foods aimed at target populations at
      high risk for diet-related diseases with an inflammatory component.

PMID- 29579980
TI  - Tayloring W/O/W emulsion composition for effective encapsulation: The role of
      PGPR in water transfer-induced swelling.
AB  - The role of the lipophilic surfactant, polyglycerol polyricinoleate (PGPR) in
      water transfer in food-grade double emulsions was investigated, and related to
      physical emulsion stability. Double (W/O/W) emulsions were prepared with various
      PGPR concentrations (0.5-5.0 wt%) in the oil phase, at initial osmotic pressure
      differences of up to 1.1 MPa between the water phases. At high PGPR
      concentrations (>2 wt%), emulsions showed good physical stability, with
      encapsulation efficiency close to 100%. It was found that PGPR is involved in
      water transfer between the water phases through reverse micelle formation by PGPR
      molecules or hydrated monomers of PGPR, and this allows for controlled swelling.
      Emulsions that are initially of low viscosity (milk-like emulsions), obtain an
      apparent viscosity of up to 3 Pa.s, and this effect can be used to tune the
      emulsion properties to the targeted application, whithout the need to gel either
      the internal or external phase.

PMID- 29579981
TI  - Location effects on the polyphenolic and polysaccharidic profiles and colour of
      Carignan grape variety wines from the Chilean Maule region.
AB  - This paper reports on a study of chemical characterization and colour parameters
      of cv. Carignan red wines from six locations and two production years of the
      Chilean Maule valley. The chemical study was performed on polyphenolic
      composition (benzoic acids, hydroxycinnamic acid derivatives, stilbenes, flavan-3
      ols, flavonols and anthocyanins) and several fractions of proanthocyanidins and
      polysaccharides. Results revealed that although significantly (p < 0.05)
      different content of anthocyanins were observed according to the production year,
      it could be possible to establish fingerprints of the different locations of the
      Maule valley wines. Thus, wines from zones closer to the Andes Mountains had
      higher content of procyanidin B3 (Caliboro), polysaccharides and cis-resveratrol
      glucoside (Loncomilla and Melozal), whereas the proximity to the Pacific Ocean
      provoked a unifying effect in chemical and colorimetric terms (Cauquenes, Sauzal
      and Huerta del Maule).

PMID- 29579982
TI  - Nutritional potential, chemical profile and antioxidant activity of Chicha
      (Sterculia striata) nuts and its by-products.
AB  - The Sterculia striata nut commonly known as chicha is consumed raw or toasted
      inBrazil but information on its chemical composition and antioxidant activity are
      scarce in the literature. In this work, the nutritional composition, minerals
      profile, lipid composition and phenolic compounds profile of chicha nuts and its
      by-products (pellicle and shell) were determined. The results showed that the
      nuts and the cake contain considerable amount of fibers and proteins and are rich
      in minerals (Fe, Mn and Cu). Oleic acid was the main fatty acid (37.8%), and PPO
      (36.0%) and POP (15.6%) were the main triacylglycerides present in the chicha
      oil. The phytosterols beta-sitosterol, stigmasteroland campesterol (1848.5MUgg-1,
      542.2MUgg-1 and 186.3MUgg-1, respectively), and the gamma-, delta-, alpha- and
      beta-tocopherol (8.85; 2.10; 1.64, and 0.11mg100g-1, respectively) were
      identified in the oil. The antioxidant activity (ABTS and FRAP assays) followed
      the order pellicle>shell>nuts (13.25 and 84.65; 8.71 and 64.3; 5.85 and
      36.79MUmolTEACg-1, respectively). The main phenolic compounds identified in the
      extracts were ellagic and ferulic acids; ellagic and protocatechuic acids; and
      protocatechuic, ellagic and methoxyphenylacetic acids for the nuts, shells and
      pellicle, respectively. A strong positive correlation was observed between total
      phenolic content and antioxidant activity determined by ABTS and FRAP assays
      (r=0.9067, p<0.01; and r=0.9584, p<0.01; respectively). Collectively, the results
      showed that the chicha is a nut of high nutritional value, rich in bioactive
      compounds.

PMID- 29579983
TI  - Controlled-release of antacids from biopolymer microgels under simulated gastric
      conditions: Impact of bead dimensions, pore size, and alginate/pectin ratio.
AB  - The highly acidic nature of the gastric fluids inside the human stomach can cause
      have health problems in certain individuals e.g., acid reflux and ulcers. Antacid
      loaded biopolymer microgels can be used to control the acidity of the gastric
      fluids, which may be useful for developing functional foods to treat these
      problems. In this study, the impact of biopolymer microgel dimensions and
      composition on the dissolution rate of encapsulated antacid was determined under
      simulated gastric conditions. The microgels were formed by injecting antacid
      (magnesium hydroxide) and biopolymers (alginate or alginate/pectin) into a
      calcium chloride solution to promote cross-linking. Microgels of varying
      dimensions were formed using either a hand-held syringe or a vibrating nozzle
      encapsulation device with different nozzle sizes. The rate of antacid dissolution
      was measured using an automatic titration device (pH stat) that added HCl
      solution into the simulated gastric fluids to maintain a constant pH of 2.5. The
      antacid dissolution rate decreased with increasing microgel diameter (300 to 1660
      MUm) and decreasing pore size (0.8 to 2.0% alginate). The slowest dissolution
      rate was observed in microgels containing 80% alginate and 20% pectin, which may
      have been due to the impact of biopolymer composition on bead dimensions and pore
      size. The results of this study may be useful for the design of biopolymer
      microgels that can control the release of antacids in the stomach, thereby
      leading to better control over the pH of the gastric fluids.

PMID- 29579984
TI  - Inter-correlation of apple firmness determinations and development of cross
      validated regression models for prediction of sensory attributes from
      instrumental and compositional analyses.
AB  - The texture of apples is paramount for determining fruit quality. This research
      explored the correlations among firmness determinations from the Sinclair iQTM
      Firmness Tester (SiQTM), the Aweta Acoustic Firmness Sensor (AFS), and eight
      measurements from the Mohr Digi-Test-2 (MDT) instrument. Assessments were
      conducted on a collection of nine apple cultivars (Ambrosia, Aurora Golden
      GalaTM, Honeycrisp, Fuji, Imperial Gala, McIntosh, Pink LadyTM, Silken,
      SalishTM), with a broad range of firmness values, in each of two years. Sensory
      analysis of the apples was conducted using a semi-trained panel (n = 10) to
      evaluate crispness, hardness, juiciness and skin toughness, in quadruplicate at
      two testing dates, providing eight data points per cultivar per year. Inter
      correlations of the instrumental firmness determinations (SiQTM, AFS, MDT)
      revealed that most values were highly correlated with one another (r > 0.500 n =
      72). This suggested that the instruments were tracking similar, but not
      identical, underlying characteristics. Multiple regression models were developed
      using the 2016 data to predict the sensory attributes from the instrumental and
      compositional (titratable acidity, soluble solids concentration, absorbed juice)
      analyses. Models with the highest R2 were cross-validated using the 2015 data.
      Accuracy of these models was evaluated using R2 and prediction standard errors
      (PSEs) - an index quantifying the difference between the predicted and actual
      values. In general, simple 1- and 2-variable models satisfactorily predicted
      hardness and crispness, with the R2 values ranging between 85 and 89%, while more
      complex non-linear models were required to predict juiciness and skin toughness.
      Correlations coefficients reported in this research allow for interconversion of
      experimental firmness data, as determined by the SiQTM, AFS and MDT. Regression
      models predicting hardness, crispness and juiciness from
      instrumental/compositional analyses, revealed that the quality factor (QF)
      variable was particularly important for estimation of textural characteristics.
      Therefore the MDT, among the instruments evaluated, was the instrument of choice
      for quality assessment of apples. Since cross-validation of the models accounted
      for a high proportion of the variance (70-82%) in a new data set with small PSEs
      (2.67-6.36) (on a 100-unit scale), the developed models were appropriate for
      estimating the apple textural attributes.

PMID- 29579985
TI  - Application of a recombinant laccase-chlorogenic acid system in protein crosslink
      and antioxidant properties of the curd.
AB  - Milk protein crosslink through the action of enzymes represents a feasible
      strategy to impart new functionalities to cheese. In this work we reported the
      effects of a laccase mediator system (LMS) on protein crosslink and antioxidant
      property of curd. The crosslinking activity of a purified recombinant laccase
      Ery4 and a commercial enzyme preparation (cLC), with three mediators was firstly
      evaluated in milk and then applied before curd manufacture. Only Ery4-LMS
      significantly increased curd weight compared to that of the control sample. SDS
      PAGE revealed that similar high molecular weight bands produced by both LMSs in
      milk were also retained in curds. The antioxidant activity recorded in curds with
      Ery4-LMS was the highest among all samples both before and after gastro
      pancreatic digestion. This is the first time that a CGA-based LMS is used in
      manufacture of curd with improved antioxidant properties. These results open new
      perspectives for dairy applications.

PMID- 29579986
TI  - Ohmic Heating: A potential technology for sweet whey processing.
AB  - The use of Ohmic Heating (OH) for sweet whey processing was investigated in this
      study. Whey samples were subjected to both different OH parameters (2, 4, 5, 7
      and 9 V.cm-1 at 60 Hz, up to 72-75  degrees C/15 s) and conventional processing
      (72-75  degrees C/15 s). Physicochemical analyses (pH), color measurements (L*,
      a*, b*), rheological properties (flow curves and particle size distribution),
      microstructure (optical microscopy), bioactive compounds (ACE and antioxidant
      capacity), microbiological characterization (mesophilic bacteria, total
      coliforms, and thermotolerant coliforms), water mobility (TD-magnetic resonance
      domain), and sensory evaluation (descriptive analysis) were carried out. The OH
      effects on sweet whey characteristics depended on the applied electric field
      intensity. Higher saturation, higher color variation (DeltaE*), and higher
      luminosity (L*) were observed in low electric fields. For bioactive compounds,
      the increase of the electric field negatively affected the preservation of the
      antioxidant capacity and the ACE Inhibitory Activity of bioactive peptides. OH
      and conventional samples exhibited a pseudo-plastic behavior (n < 1). OH
      performed at 4 and 5 V.cm-1 was able to provide similar levels of sensory profile
      and higher volatile compounds levels. The results suggested the OH technology as
      an interesting alternative to whey processing.

PMID- 29579987
TI  - Inactivation kinetics of Escherichia coli in cranberry juice during multistage
      treatment by electric fields.
AB  - The inactivation of Escherichia coli inoculated in cranberry juice by processing
      with radio frequency electric fields was studied. E. coli ATCC 35218 was chosen
      among three non-pathogenic strains based on its ability to survive in low pH
      cranberry juice. Studies were conducted by measuring the survival population when
      changing the electric field strength between 2.2 and 13.2 kV cm-1, number of
      treatment stages from 1 to 6 and flow rates between 13 and 25 L h-1 at moderate
      temperatures of 20, 30 and 40  degrees C. A minimum inactivation of 5-log
      reduction, as requested by the Food and Drug Administration (FDA), can be
      achieved by increasing the number of treatment stages, temperature or both. At 40
      degrees C and 6 treatment stages, 6.57 +/- 0.02 log CFU ml-1 reduction in the
      initial population of E. coli (ATCC 35218) was obtained. At a constant electric
      field, increasing the temperature produced higher microbial inactivation,
      consuming lower radio frequency energy input, than increasing the number of
      treatment stages. Furthermore, a primary model that accounts for the combined
      effect of time and electric field is proposed. The model represented the
      sigmoidal curve composed of shoulder, log-linear and tailing sections as observed
      when changing electric fields. A secondary model that accounts for the effect of
      temperature and flow rate on the primary model constants is also proposed. The
      combined primary and secondary models were found to fit the data well with a high
      coefficient of determination (R2 = 0.965). The proposed model can be extended to
      kinetic models for pulsed electric fields.

PMID- 29579988
TI  - Assessment of the color modulation and stability of naturally copigmented
      anthocyanin-grape colorants with different levels of purification.
AB  - Grape skins or their by-products from wine production are rich sources of
      anthocyanins and various colorless phenolics, depending on the grape variety.
      Phenolics have strong antioxidant and anthocyanin stabilizing properties and help
      to produce functional anthocyanin colorants with improved stability. This study
      aimed to assess differences in color expression and stability of anthocyanin
      colorants from red grape varieties naturally copigmented and with different
      levels of purity and to compare them to synthetic FD&C Red No. 3. Model juice
      systems were prepared at pH 3.5 with anthocyanins and phenolic copigments
      extracted from four Vitis vinifera grape varieties ('Tempranillo', 'Syrah', 'C.
      Sauvignon', and 'Graciano') both crude and purified by C18 solid phase
      extraction. Attention was focused on differential colorimetry and phenolic
      composition related to the color. Degradation kinetics of total color were also
      studied during storage of 17 days in darkness at 25  degrees C. Grape variety
      significantly influenced pigment yield, proportion of acylation, and proportion
      of copigments:pigments ratios in crude extracts; purification modulated the
      copigment:pigment ratios. This proportion was related to perceptible color
      variability among colorants and to different stabilities. With the same pigment
      content, grape varieties richer in skin copigments and higher copigment/pigment
      ratios ('Syrah' and 'Tempranillo') produced more intensely colored crude extracts
      whose tonalities ranged from reddish ('Graciano') to red-bluish ('Syrah'),
      depending on the proportion of acylation. Increasing the purity of the pigments
      diminished the color variability due to variety, making them less vivid and
      visually more similar to one another and also to the synthetic colorant.
      Degradation kinetic studies showed that unpurified grape colorants had higher
      color stability over time, with the greatest stabilizing effects achieved with
      varieties richer in skin flavonols ('Tempranillo' and 'Syrah').

PMID- 29579989
TI  - Fabrication of beta-conglycinin-stabilized nanoemulsions via ultrasound process
      and influence of SDS and PEG 10000 co-emulsifiers on the physicochemical
      properties of nanoemulsions.
AB  - Nanoemulsions stabilized by beta-conglycinin (7S), beta-conglycinin/sodium
      dodecyl sulfate (SDS) and beta-conglycinin/polyethylene glycol 10000 (PEG 10000)
      were produced via ultrasound process. All the nanoemulsions showed the desired
      mean particle size and narrow size distribution. The effects of pH, ionic
      strength and temperature on the properties of the nanoemulsions were
      investigated, and the long-term stability of the fabricated nanoemulsions was
      also monitored during storage at 4  degrees C. The nanoemulsions prepared by 7S
      exhibited a good stability over various pH (<4 or >5), ionic strength (0-500 mM
      NaCl), thermal treatment (80  degrees C) and storage time (0-45 days). The
      stability of 7S nanoemulsions was enhanced by adding SDS, whereas reduced by
      adding PEG 10000, which could be attributed to the higher zeta-potential in the
      present of SDS leading to stronger electrostatic repulsion against droplet
      flocculation, whereas opposite was observed for the addition of PEG 10000.
      Therefore, this study provided important evidences for the fabrication of
      nanoemulsions using protein/surfactant complexes as the emulsion stabilizer via
      ultrasound process.

PMID- 29579990
TI  - Stability and release behavior of encapsulated flavor from spray-dried
      Saccharomyces cerevisiae and maltodextrin powder.
AB  - Yeast cells (Saccharomyces cerevisiae), from which beta-glucans have been
      partially extracted, were used to encapsulate flavor inside the lipid bilayer
      membrane as natural encapsulant. The focus of this study was to investigate the
      release and stability of flavors (d-limonene and ethyl hexanoate) encapsulated in
      yeast cells and maltodextrin (MD) (DE = 19) by spray drying. The release behavior
      of encapsulated flavors from yeast cells was measured at 40, 60, 80, and 105 
      degrees C with different moisture content (0, 50, 100, and 200% of powder). Water
      affected flavor release from the yeast cells. The release rate constants were
      correlated using Gaussian distribution of the activation energy of the release
      rate constants. The release of d-limonene from the spray-dried MD powder showed a
      different trend than that of yeast cells at various temperatures. The activation
      energies of the release rate constant for ethyl hexanoate and d-limonene from
      yeast were 55 and 49 kJ/mol, respectively, under a wet condition. The formation
      rates of limonene oxide and carvone were slower in yeast than that of MD powder
      at 30  degrees C after 2 months.

PMID- 29579991
TI  - Valorization of okara oil for the encapsulation of Lactobacillus plantarum.
AB  - Oil-in-water (O/W) emulsions of okara oil-caseinate (1:2; 1:3 and 1:4 O/W ratios)
      were used to encapsulate Lactobacillus plantarum CIDCA 83114. Once encapsulated,
      microorganisms were freeze-dried or spray-dried, and observed by scanning
      electronic and confocal microscopies. A physical characterization of the
      dehydrated capsules was carried out by determining their moisture content, water
      activity, particle size, polydispersity index and zeta potential. Determining the
      induction times and peroxide values provided information about their
      susceptibility to oxidation. In turn, bacterial stability was analyzed by plate
      counting before and after freeze-drying and spray-drying, and during storage at 4
      degrees C. Spray-dried emulsions had lower Z-sizes and polydispersity indexes,
      higher induction times and lower peroxide values than the freeze-dried ones, thus
      resulting better systems to protect L. plantarum CIDCA 83114. In addition, the
      culturability of spray-dried bacteria did not decrease neither after spray-drying
      nor up to 60days of storage at 4 degrees C. The results showed that the better
      physical-chemical stability of spray-dried capsules determined the greater
      stability of microorganisms. This demonstrates the importance of defining
      adequate emulsions' formulations for an efficient encapsulation of
      microorganisms, with promising applications in the development of novel
      functional foods.

PMID- 29579992
TI  - Mild high hydrostatic pressure pretreatments applied before soaking process to
      modulate wholegrain brown rice germination: An examination on embryo growth and
      physicochemical properties.
AB  - This investigation aimed to examine the effects of a novel processing pattern,
      combining high hydrostatic pressure (HHP) with germination, on the embryo growth
      and physicochemical characteristics of wholegrain brown rice (WBR). WBR grains
      were firstly subjected to mild HHP stress (30-90 MPa/5 min) and then incubated at
      37  degrees C for 52 h for obtaining germinated samples (GBR). The results showed
      that HHP shock resulted in a delayed embryo growth of WBR grains, maintaining
      acceptable sprouting rates ranging from 65% to 76% when germination was finished.
      The contents of gama-aminobutyric acid in GBR were greatly increased responding
      to HHP stress, showing pressure intensities dependent. Total digestible and
      resistant starch contents in samples stressed at 60/90 MPa were decreased, mainly
      associated with high pressure-induced amorphization as revealed by SEM imaging
      and FTIR, which promoted starch hydrolysis during germination. Besides, the
      levels of zinc and iron were influenced by HHP pretreatments due to the high
      pressure-mediated degradation behavior for phytic acids. The storability of HHP
      stressed GBR grains was significantly enhanced through reducing free fatty acids
      formation and maintaining color stability during a storage testing. These results
      obtained from the current work demonstrated that mild HHP stress pretreatment
      prior to germination process could be used as a promising strategy to modulate
      certain physicochemical characteristics of WBR products.

PMID- 29579993
TI  - Metabolic variation and cooking qualities of millet cultivars grown both
      organically and conventionally.
AB  - Millet plays a major role in food security in Africa and Asia. In addition to
      being a rich source of nutrients, millet contains many phytochemicals that are
      potentially beneficial for human health, and several of these compounds are
      related to its cooking properties. In this study, 172 metabolites and 3 cooking
      quality traits of millet from the same two cultivars grown both organically and
      conventionally were analyzed. The results indicated that the differences in the
      metabolities and cooking quality of the millets could be attributed mostly to the
      cultivar and whether the millet was grown conventionally or organically. Organic
      growing conditions only enhanced the accumulation of some carbohydrates such as
      fructose and glucose. Therefore, cultivar selection was important in organic
      millet cultivation. The relationships between metabolites and cooking quality
      traits showed that, overall, 57.43% of the variation in the cooking quality
      matrix was explained by metabolome matrix, which indicated that some chemical
      compounds could also be used to evaluate the cooking qualities of millet. These
      results could contribute to breeding millet to improve its the nutritional
      properties and cooking qualities.

PMID- 29579994
TI  - Standardizing the analysis of phenolic profile in propolis.
AB  - The analysis of propolis is controversial, hampering the comparison of its
      biological properties and estimation of its commercial value. This work evaluates
      the effectiveness of combining maceration and ultrasonication extraction
      techniques on the yield, total phenol content (Folin-Ciocalteau) and the specific
      phenolic compounds (HPLC-UV), on propolis from different origins. The extraction
      method was not significant in any case; therefore ultrasonication is recommended
      (time-saving) but only when a double extraction is performed. Propolis yield
      varies significantly between samples, as it includes impurities, consequently the
      results should be expressed considering the yield (as balsam) instead of raw
      propolis. Of the 13 quantified phenolic compounds, CAPE and pinocembrin (803 and
      701 mg/g balsam) stand out. The phenolic profile of a propolis must be fixed
      using both total phenol content (with a consensus reference compound) and the
      specific phenolic compounds, since the latter provides information about
      compounds that can play a significant antioxidant role.

PMID- 29579995
TI  - Metabolomics approach for understanding geographical dependence of soybean leaf
      metabolome.
AB  - The soybean plant (Glycine max) is widely used as an ingredient in various foods,
      nutraceuticals and cosmetics, due to their diverse bioactive compounds. Their
      metabolic compositions are likely affected by environmental conditions during
      growth. To investigate the influence of different environmental conditions on the
      metabolite composition of soybean leaves, we cultivated soybean (G. max Sinhwa)
      in the southernmost island and volcanic region of Korea, and in the central
      section and limestone region of the Korean peninsula. Comprehensive metabolite
      variations of their leaves were analyzed through 1H NMR-based metabolomics
      approach. With marked differences in soil compositions and climatic conditions
      between the two growing areas, differences in accumulations of pinitol and
      diverse flavonoids were noted between the soybean leaves, reflecting the distinct
      metabolism of soybean plants for physiological adaptation toward different
      environmental conditions. Therefore, the current study highlights the
      geographical dependences of diverse soybean leaf metabolites for developing
      biofunction-enhanced soybean products.

PMID- 29579996
TI  - Effects of sonication on the physicochemical and functional properties of walnut
      protein isolate.
AB  - The objective of this study was to investigate the impact of high-intensity
      ultrasound treatment (sonication) on the molecular, physicochemical, and
      functional properties of walnut protein isolate. Aqueous walnut protein
      suspensions were sonicated at varying power levels (200, 400 or 600 W) and times
      (15 or 30 min), and then any alternations in protein structure and properties
      were determined. SDS-PAGE demonstrated that there were no changes in protein
      electrophoretic patterns, indicating that sonication did not break covalent
      bonds. Circular dichroism spectroscopy indicated a small change in protein
      secondary structure after sonication, with a decrease in alpha-helix and increase
      in beta-sheet, beta-turn, and random coil content. There was an increase in
      surface free sulfhydryl (SH) groups and a decrease in fluorescence intensity
      after sonication, indicating that appreciable changes in tertiary structure
      occurred. Ultrasound reduced the size of the particles in aqueous walnut protein
      dispersions as confirmed by static light scattering and scanning electron
      microscopy, suggesting that sonication dissociated protein aggregates. Moreover,
      the water-solubility (+22%), emulsifying activity index (+26%), and emulsifying
      stability index (+41%) all increased after sonication. These results suggest that
      sonication is a valuable tool for improving the functional attributes of walnut
      proteins.

PMID- 29579997
TI  - Cold atmospheric pressure ambient air plasma inhibition of pathogenic bacteria on
      the surface of black pepper.
AB  - In present study, the inhibition effect of low temperature plasma on Bacillus
      subtilis, Escherichia coli, Salmonella Enteritidis and B. subtilis endospores
      inoculated on the surface of black peppercorns was studied. Plasma was generated
      by Diffuse Coplanar Surface Barrier Discharge (DCSBD) at atmospheric pressure in
      ambient air. Plasma treatment time of 300 s led to log10 CFU/g reduction of B.
      subtilis from 7.36 to 2.30 and B. subtilis endospores from 4.42 to 2.39. Plasma
      treatment reduced the number of E. coli and Salmonella Enteritidis to below
      detection level (1.0 log10 CFU/g) from initial populations of 7.45 log10 CFU/g
      and 7.60 log10 CFU/g, respectively. The inactivation kinetics was explained by
      Weibull model. Decimal reduction times (D-values) for B. subtilis, E. coli,
      Salmonella Enteritidis, and B. subtilis endospores were determined as 43 s, 47 s,
      58 s, and 142 s, respectively. The surface morphology observed by Scanning
      Electron Microscopy showed no significant changes after the plasma treatment. The
      influence of plasma on chemical bonds on the surface and inside the peppercorns
      was studied by Attenuated Total Reflectance - Fourier Transform Infrared
      Spectroscopy.

PMID- 29579998
TI  - 1H NMR-based metabolomic profiling for identification of metabolites in Capsicum
      annuum cv. mirasol infected by beet mild curly top virus (BMCTV).
AB  - Beet mild curly top virus (BMCTV) is associated with an outbreak of curly top in
      chili pepper, tomato and other Solanaceae species, which can cause severe crop
      losses. The aim of this work was to obtain the 1H NMR metabolomic profiling of
      both healthy chili peppers (cv. mirasol) and infected chili peppers with BMCTV in
      order to find chemical markers associated to the infection process. Significant
      differences were found between the two groups, according to principal component
      analysis and orthogonal projections to latent structure discriminant analysis.
      Compared to the asymptomatic peppers, the symptomatic fruits had higher relative
      abundance of fructose, isoleucine, histidine, phenylalanine and tryptophan.
      Contrarily, the asymptomatic samples showed greater amounts of malonate and
      isobutyrate. These results suggest that in diseased chili peppers there are
      metabolic changes related to the viral acquisition of energy for replication and
      capsid assembly. This is the first study describing the chemical profiling of a
      polar extract obtained from Capsicum annuum infected by BMCTV under open field
      conditions.

PMID- 29579999
TI  - Influence of in vitro digestion process on polyphenolic profile of skin grape
      (cv. Italia) and on antioxidant activity in basal or stressed conditions of human
      intestinal cell line (HT-29).
AB  - White table grape cv. Italia is a typical component of the Mediterranean diet and
      a source of phenolic compounds, particularly abundant in the skin portion. The
      aim of this study was to characterize the phenolic profile of the table grape
      skin and to assess its stability after the in vitro digestion process. The main
      phenolic compounds identified by the HPLC-DAD analysis were: procyanidin B1,
      caftaric acid, catechin, coutaric acid, quercetin 3-glucuronide and quercetin 3
      glucoside. All compounds showed a good stability after in vitro digestion (from
      43 to 80%). Moreover, the influence of grape skin polyphenols on the modulation
      of ROS and GSH levels was evaluated in basal and in stressed conditions on human
      intestinal cells (HT-29). In basal conditions, a higher polyphenol concentrations
      exerted pro-oxidant effect corresponding to high ROS level and low GSH content.
      This effect was probably due to the polyphenolic oxidation in cell culture
      condition with consequent production of hydrogen peroxide. Otherwise, in stressed
      conditions, grape skin polyphenols exerted antioxidant effects up to 1.3 * 10-6
      MUg/g and restored the stress-related GSH reduction. The in vitro digestion
      process attenuated the biological effect of grape skin polyphenols on intestinal
      cell line (HT-29). In conclusion, grape skin polyphenols showed different
      behavior in relation to their concentrations and to the intracellular ROS levels.

PMID- 29580000
TI  - The effect of dense phase carbon dioxide on the conformation of hemoglobin.
AB  - Dense phase carbon dioxide (DPCD) sterilization is a non-thermal sterilization
      technology used to process heat-sensitive foods. Although nutritional and
      sensorial quality of food is preserved while unwanted microbial activity is
      reduced during DPCD sterilization, the effect on protein structure remains
      unclear. In this work, the effect of DPCD on the higher order structure and
      fluorescence properties of Hemoglobin (Hb) was investigated. The different
      conditions assessed during DPCD processing included variation in pressure, pH and
      heating conditions. Results from this study showed an inversely proportional
      correlation between alpha-helical content of Hb and pressure. As the pressure was
      lowered, the levels of alpha-helical content increased. The increased levels of
      alpha-helix correlated with a lower fluorescence intensity and a limited redshift
      in the fluorescence emission wavelength. TEM imaging showed that DPCD processing
      resulted in Hb with larger molecular diameters, which became smaller as the
      pressure increased. Interestingly, after 7-day storage at 4  degrees C, an
      increase in alpha-helical content was observed. Results from this work show that
      DPCD sterilization does impact the conformation of hemoglobin, with a notable
      impact on secondary and tertiary structure.

PMID- 29580001
TI  - Comparison of rapid descriptive sensory methodologies: Free-Choice Profiling,
      Flash Profile and modified Flash Profile.
AB  - Rapid sensory methods have been developed as alternatives to traditional sensory
      descriptive analysis methods. Among them, Free-Choice Profiling (FCP) and Flash
      Profile (FP) are two that have been known for many years. The objectives of this
      work were to compare the rating-based FCP and ranking-based FP method; to
      evaluate the impact of adding adjustments to FP approach; to investigate the
      influence of the number of assessors on the outcome of modified FP. To achieve
      these aims, a conventional descriptive analysis (DA), FCP, FP and a modified
      version of FP were carried out. Red wines made by different grape maturity and
      ethanol concentration were used for sensory testing. This study showed that DA
      provided a more detailed and accurate information on products through a
      quantitative measure of the intensity of sensory attributes than FCP and FP.
      However, the panel hours for conducting DA were higher than that for rapid
      methods, and FP was even able to separate the samples to a higher degree than DA.
      When comparing FCP and FP, this study showed that the ranking-based FP provided a
      clearer separation of samples than rating-based FCP, but the latter was an easier
      task for most assessors. When restricting assessors on their use of attributes in
      FP, the sample space became clearer and the ranking task was simplified. The FP
      protocol with restricted attribute sets seems to be a promising approach for
      efficient screening of sensory properties in wine. When increasing the number of
      assessors from 10 to 20 for conducting the modified FP, the outcome tended to be
      slightly more stable, however, one should consider the degree of panel training
      when deciding the optimal number of assessors for conducting FP.

PMID- 29580002
TI  - Improved freeze drying efficiency by ice nucleation proteins with ice morphology
      modification.
AB  - This study aims to use ice nucleation proteins (INPs) as a novel approach to
      improve the efficiency of freeze drying process and investigate the related
      mechanism of ice morphology. Our results show that INPs can significantly improve
      freeze drying efficiency with increased primary drying rate under the increase of
      INP concentration from 0 to 10-2mg/mL. Moreover, such improvement was more
      significant at higher subzero freezing temperatures with the addition of INPs,
      when the control samples were unable to freeze. Those improvements further lead
      to reduced total drying time, which suggests an estimated total energy saving of
      28.5% by INPs. Our ice morphology results indicate the ability of INPs to alter
      ice morphology with lamellar ice structure and larger crystal size, which both
      show linear relationships with primary drying rate. The results further suggest
      that these ice morphology characteristics induced by INPs are very likely to
      facilitate the water vapor flow and improve the sublimation rate. Additionally,
      the increase of freeze drying efficiency can also be achieved by INPs in other
      food systems like coffee and milk with elevated primary drying rate. The results
      of this study suggest great potential of using INPs to improve the efficiency of
      freeze drying process for a wide range of food products and other related
      applications. This study also provides new insights into the relationship between
      process efficiency and ice morphology.

PMID- 29580003
TI  - Kinetic modelling of ascorbic and dehydroascorbic acids concentrations in a model
      solution at different temperatures and oxygen contents.
AB  - The degradation kinetics of vitamin C (ascorbic and dehydroascorbic acids, AA and
      DHA) were determined under controlled conditions of temperature (50-90  degrees
      C) and oxygen concentrations in the gas phase (10-30% mol/mol) using a specific
      reactor. The degradation of vitamin C in malate buffer (20 mM, pH 3.8), mimetic
      of an apple puree, was assessed by sampling at regular intervals and
      spectrophotometric quantification of AA and DHA levels at 243 nm. The results
      showed that AA degradation increased with temperature and oxygen concentration,
      while DHA exhibited the behaviour of an intermediate species, appearing then
      disappearing. A kinetic model was successfully developed to simulate the
      experimental data by two first order consecutive reactions. The first one
      represented AA degradation as a function of temperature and concentration in
      dissolved oxygen, and the second reflected DHA degradation as a function of
      temperature only, both adequately following Arrhenius' law.

PMID- 29580004
TI  - Application of metabolomics profiling in the analysis of metabolites and taste
      quality in different subtypes of white tea.
AB  - Three subtypes of white tea, Silver Needle (SN), White Peony (WP), and Shou Mei
      (SM), differ in their taste, aroma, bioactivity, and commercial value. Here, a
      metabolomics investigation on the chemical compositions combining taste
      equivalent-quantification and dose-over-threshold (DoT) determination on the
      taste qualities were applied to comprehensively characterize the white tea
      subtypes for the first time. Significant differences in the contents of
      catechins, dimeric catechins, amino acids, phenolic acids, flavonol/flavone
      glycosides, and aroma precursors were observed among these 3 white teas.
      Metabolite content comparison and partial least-squares (PLS) analysis suggest
      that theanine, aspartic acid, asparagine, and AMP were positively correlated with
      the umami taste in white tea, and flavan-3-ols, theasinensins, procyanidin B3,
      and theobromine had positive correlations with higher bitterness and astringency
      tastes. In addition, puckering astringent (-)-epigallocatechin gallate (EGCG), (
      )-epicatechin gallate (ECG) and theogallin, bitter-tasting caffeine, and the
      mouth-drying/velvety-like astringent gamma-aminobutyric acid (GABA) were
      identified as key taste compounds of white tea infusion by absolute
      quantification and DoT factor calculations. This work provided systematic and
      comprehensive knowledge on the chemical components, taste qualities, and sensory
      active metabolites for the subtypes of white tea.

PMID- 29580005
TI  - Discrimination of Tunisian and Italian extra-virgin olive oils according to their
      phenolic and sterolic fingerprints.

PMID- 29580006
TI  - The ultrasound assisted hydration as an opportunity to incorporate nutrients into
      grains.
AB  - Hydration is an important but long step in processing beans. Consequently, any
      ways of taking advantage of this processing time are desirable. One possibility
      is to fortify the beans during the hydration process, especially with water
      soluble nutrients. This work studied the incorporation of iron into beans during
      hydration with and without ultrasound, describing the kinetics of water and iron
      uptake, the entrance pathway and its effect on germination and the cooking
      process. For that, carioca beans were soaked in ferrous sulfate solution (0.271%
      w/v) with and without ultrasound (91 W/L; 25 kHz) at 25  degrees C. It was
      demonstrated that iron could be incorporated during the hydration process,
      describing a similar kinetics behavior to the water uptake. In addition,
      ultrasound accelerated this process, achieving 60.1 mg Fe/100 g w.b. after 510
      min of process, in contrast to 34.4 mg Fe/100 g w.b. when the beans were hydrated
      without ultrasound. Finally, by hydrating the beans with ferrous sulfate, the
      cooking process was accelerated, which is desirable. However, the capacity for
      germination of the beans was reduced. In conclusion, the hydration process time
      can be used to fortify the beans with iron (and, possibly, other water-soluble
      nutrients). Nevertheless, future studies must be performed to determine if the
      incorporated iron is bioavailable and bioaccessible, as well as how relevant this
      approach is as a nutritional policy.

PMID- 29580007
TI  - Functional characterization of Lactobacillus plantarum ITEM 17215: A potential
      biocontrol agent of fungi with plant growth promoting traits, able to enhance the
      nutritional value of cereal products.
AB  - In this work, we explored the potential of 25 Lactobacillus plantarum strains
      isolated from cereals and milk-based products, testing characteristics related to
      antifungal activity and to nutritional quality. The tested strains demonstrated
      interesting beneficial traits, such as the ability to utilize fructo
      oligosaccharides, prebiotic substances that help probiotic microorganisms to grow
      in the human gut, and to reduce phytate, an antinutrient present in cereal
      sector. Regarding mould inhibition, we highlighted the ability of the strains to
      inhibit Penicillium roqueforti, Mucor circinelloides and mycotoxinogenic moulds
      associated with cereal grains as Aspergillus flavus, A. niger, Fusarium
      verticillioides. Moreover, a moderate reduction of the bioavailability of
      aflatoxin AFB1 was detected. The selected L. plantarum strain ITEM 17215, showed
      a strong inhibitory ability towards fungal growth and was able to produce 1,2
      dihydroxybenzene, benzoic acid, p-hydroxyphenyllactic acid and 3-phenyllactic
      acid. The latter compound, already described as efficient antifungal inhibitor,
      was the most abundant and its concentration was further increased by adding
      phenylalanine and phenylpyruvic acid in the growth medium. The metabolites
      produced by strain ITEM 17215 could also be related to the ability of the strain
      to induce cereal germination and promote plant growth. This aspect, not yet
      investigated in L. plantarum, could have interesting applications in the agro
      food sector.

PMID- 29580008
TI  - Water-in-oil-in-water emulsion obtained by glass microfluidic device for
      protection and heat-triggered release of natural pigments.
AB  - Anthocyanins and norbixin are natural pigments used in food; however, they are
      unstable. The aim of this study was to evaluate the microencapsulation technique
      to protect these pigments. Elderberry extract (source of anthocyanins) and
      norbixin were encapsulated using a microfluidic device with palm oil as middle
      phase in a water-in-oil-in-water emulsion. The formulations were characterized
      for morphology, particle size, encapsulation efficiency, zeta potential, color
      release under heating, Fourier transform infrared spectrophotometry, and color
      stability under different conditions. Spherical, mononucleated microcapsules,
      with particle size of 187-190 MUm (elderberry) and 164-184 MUm (norbixin), and
      with encapsulation efficiencies values of 47.80-54.87% (elderberry) and 49.18
      74.73% (norbixin) were obtained. The formulations showed high color retention,
      with the encapsulated elderberry extract stored at pH 3.0 being the most stable.
      This study shows that the microencapsulation of these pigments using a
      microfluidic device provided protection, and represents a new method for
      anthocyanins and norbixin delivery in foods.

PMID- 29580009
TI  - In vitro and in vivo anti-diabetic and anti-hyperlipidemic effects of protein
      hydrolysates from Octopus vulgaris in alloxanic rats.
AB  - This study aims to examine the effects of non-hydrolyzed octopus (Octopus
      vulgaris) muscle proteins (NHOPs) and their hydrolysates (OPHs) on alloxan
      induced diabetes in Wistar rats (AIDR). Animals were allocated into seven groups
      of six rats each: control group (C), diabetic group (D) and diabetic rats treated
      with acarbose (D + Acar), non-hydrolyzed octopus proteins (D + NHOPs) and octopus
      proteins hydrolysates (D + OPHs) groups. The diabetic rats presented a
      significant increase in glycemic status such as alpha-amylase activity (in
      plasma, pancreas and intestine), hepatic glycogen, blood glucose and glycated
      hemoglobin (HbA1c) levels, as well as a significant decrease in the levels of
      plasma insulin and total hemoglobin compared to control group. In addition,
      plasma and liver contents in total cholesterol, triglycerides and LDL-cholesterol
      significantly increased in AIDR compared to control group. However, the daily
      administration of OPHs for 30 days improved the glucose tolerance test, the
      glycemic status of diabetic rats and corrected the lipid profiles. Further, a
      significant increase in the activities of alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well
      as in the level of plasma bilirubin on diabetic status was observed, indicating
      considerable hepatocellular injury. OPHs treatment was found to attenuate the
      increased activities of the plasma enzymes produced by diabetes and caused a
      subsequent recovery towards normalization compared to the control group. By
      contrast, the NHOPs treatment was found to increase the glucose metabolic
      disorders in AIDR. These beneficial effects of OPHs were confirmed by
      histological findings in the hepatic and pancreatic tissues of diabetic treated
      rats. Indeed, they avoid lipid accumulation in the hepatocytes and protect the
      pancreatic beta-cells from degeneration. Our results thus suggest that OPHs may
      be helpful in the preventing from diabetic complications by reversing
      hepatotoxicity.

PMID- 29580010
TI  - Physicochemical characterization of native and modified sodium caseinate- Vitamin
      A complexes.
AB  - Native and modified sodium caseinate- Vitamin A complexes {Sodium caseinate- Vit
      A complex by stirring (NaCas-VA ST), succinylated sodium caseinate- Vit A complex
      by stirring (SNaCas-VA ST), reassembled sodium caseinate- Vit A complex (RNaCas
      VA) and reassembled succinylated sodium caseinate- Vit A complex (RSNaCas-VA)}
      were prepared and characterized for their physicochemical characteristics e.g.
      particle size, zeta potential, turbidity analysis and tryptophan intensities
      which confirmed structural modification of both native (NaCas-VA ST) and modified
      (SNaCas-VA ST, RNaCas-VA and RSNaCas- VA) proteins upon complex formation with
      vitamin A. Binding of vitamin A to milk protein reduced the turbidity caused by
      vitamin A, however, the particle size and zeta potential of milk protein
      increased after complexation. Microstructure details of NaCas (spray dried)
      showed uniform spherical structure, however, other milk proteins and milk protein
      Vit A complexes (freeze dried) showed broken glass and flaky structures. Tiny
      particles were observed on the surface of reassembled protein and reassembled
      protein- Vit A complexes. Binding of vitamin A to milk protein did not have an
      influence on the electrophoretic mobility and elution profile (RP-HPLC).

PMID- 29580011
TI  - The effect of organic wheat flour by-products on sourdough performances assessed
      by a multi-criteria approach.
AB  - In this study, we determined the effect of organic (i) flour ash content (1%
      1.4%) and (ii) flour by-product addition (bran, shorts and germ) on sourdough
      performances. After five consecutive back-sloppings, sourdough was used for bread
      making and its bread-related properties were assessed. No effect of flour
      composition factors (i & ii) on sourdough lactic acid bacteria and yeasts were
      highlighted. Nonetheless, they greatly altered lactic acid and acetic acid
      sourdough contents from 6.9 to 17.4 g/kg and from 0.9 to 2.2 g/kg, respectively.
      The flour ash content (i) had a significant and positive effect on sourdough
      acidity and CO2 production. Bread made with sourdough with a high ash content had
      a significantly higher acidity and specific volume. These physicochemical
      differences between breads were perceived by sensory evaluation in a significant
      way. Sourdough supplemented (ii) with germ had higher lactic acid and carbon
      dioxide contents than sourdough supplemented with bran and shorts. Hence, flour
      composition, combining ash content and flour by-products, appears to be an
      effective factor to obtain a better control of sourdough performances.

PMID- 29580013
TI  - Influence of enzymatic and chemical interesterification on crystallisation
      properties of refined, bleached and deodourised (RBD) palm oil and RBD palm
      kernel oil blends.
AB  - Interesterification reaction involves rearrangement of the fatty acid radicals on
      the glycerol backbone, either randomly (chemical interesterification) or
      regioselectivity (enzymatic interesterification). Refined, bleached and
      deodourised palm oil (RBDPO) and palm kernel oil (RBDPKO) were blended in ratios
      from 25:75 to 75:25 (wt/wt). All blends were subjected to enzymatic (EI) and
      chemical interesterification (CI) using Lipozyme TL IM (4% w/w) and sodium
      methoxide (0.2% m/m) as the catalysts, respectively. The effect of EI and CI on
      the triacylglycerol (TAG) composition, thermal behaviour, polymorphism, crystal
      morphology and crystallisation kinetics were studied. The aim of this research is
      to characterise the nature of crystals in food product for certain desired
      structure. The crystallisation behaviour discussed in this study involves
      microstructure (PLM), polymorphism (XRD), thermal properties and crystallisation
      kinetics by DSC. The alteration in TAG composition was greater after CI as
      compared to EI with the reduction of LaLaLa (from 11.00% to 5.15%) and POO (from
      14.28% to 4.87%). The DSC complete melting and crystallisation temperature of
      blend with 75% PO increased after CI, from 39.58  degrees C to 41.67  degrees C
      and from -30.84  degrees C to -28.33  degrees C, respectively. EI contributed to
      finer crystals than CI. However, the beta' and beta polymorph mixture and
      crystallisation kinetics (n = 2) of PO-PKO blends did not change after CI and EI.
      The knowledge on controlling crystallisation of RBDPO and RBDPKO blends is vital
      for proper processing condition like margarine production.

PMID- 29580012
TI  - Degradation of beta-casomorphins and identification of degradation products
      during yoghurt processing using liquid chromatography coupled with high
      resolution mass spectrometry.
AB  - Liquid chromatography-high resolution mass spectrometry (LC-HRMS) was used to
      investigate the degradation of beta-casomorphin 5 (beta-CM5) and beta-casomorphin
      7 (beta-CM7) by Streptococcus thermophilus and/or Lactobacillus delbrueckii ssp.
      bulgaricus, and to identify the degradation products forming during yoghurt
      processing. Bovine UHT milk was fermented with: (i) a single strain of L.
      delbrueckii ssp. bulgaricus, (ii) a single strain of S. thermophilus and (iii)
      the mixture of S. thermophilus and L. delbrueckii ssp. bulgaricus to pH4.5 and
      then stored at 4 degrees C for 1 and 7days. Results showed that L. delbrueckii
      ssp. bulgaricus and/or S. thermophilus completely degraded beta-CM5 and beta-CM7
      upon fermentation to pH4.5 and degradation products were significantly influenced
      by bacteria strains and storage time. Four peptides, beta-CNf60-61 (YP), beta
      CNf62-63 (FP), beta-CNf64-66 (GPI) and beta-CNf62-66 (FPGPI) were tentatively
      identified through high resolution MS/MS experiments; however, it was not
      possible to confirm if either milk protein or beta-casomorphins was a source
      releasing these peptides. Nonetheless, in this study peptides YP and GPI were
      released by L. delbrueckii ssp. bulgaricus. This is the first time GPI has been
      identified and thus future investigation of its bioactivity is warranted.

PMID- 29580014
TI  - Profile changes in banana flavour volatiles during low temperature drying.
AB  - Headspace gas chromatography mass spectrometry (HS-GC-MS) was used to measure
      changes in selected volatile flavour compounds in fresh banana during low
      temperature heat pump drying. Ten compounds from a range of chemical classes were
      measured during drying at three different drying conditions. Ester compounds were
      found to be the most affected, with losses varying from 25 to 87% during drying.
      Three patterns of depletion were observed in this study. Ester and aldehyde
      levels reduced quickly during the early stages of drying, but levels stabilised
      at non-zero values towards the end of drying; alcohol levels initially increased,
      then decreased and stabilised; whilst high molecular weight compounds, such as
      elemicine and eugenol, were not affected significantly. Selective diffusion and
      volatility affected the degree of flavour retention.

PMID- 29580015
TI  - Product involvement and consumer food-elicited emotional associations: Insights
      from emoji questionnaires.
AB  - Individual differences in food-related consumer behaviour are well documented,
      but lack thorough exploration in relation to product-elicited emotional
      associations. In this research, focus is directed to product involvement as a
      factor that modulates emotional associations to tasted products (dried fruit, n =
      4) and written descriptions of consumption situations (drinking red wine, cooking
      dinner using seafood). Emoji questionnaires were used (as check-all-that-apply
      questions: CATA), and across two studies with consumers in New Zealand (n = 352)
      and China (n = 450), higher levels of involvement were associated with more
      positive emotional associations. For example, consumers with higher involvement
      for dried fruit used emoji with positive meanings (e.g., face savouring delicious
      food (), smiling face with heart-shaped eyes () and smiling face with smiling
      eyes () more frequently than those with lower levels of involvement. Conversely,
      emoji with negative or neutral meanings (e.g., confused face (), confounded face
      (), neutral face ()), were more frequently used by consumers with lower levels of
      product involvement. The number of significant differences between the samples of
      dried fruit were lower in the less involved consumer segment, and these
      consumers, on average, used less emoji to characterise the samples. A similar
      pattern of results were established for the written stimuli, which were used with
      Chinese consumers. For example, in the segment with greater involvement with
      seafood, associations to emoji with positive meanings were higher when responding
      to the situation "cooking dinner using frozen seafood as one of the ingredients."
      In the case of "drinking French red wine," the strategy used to define segments
      (median vs. triadic split of summed involvement scores) additionally influenced
      the results, and bigger differences were established when comparing more discrete
      segments (two extreme groups following triadic split).

PMID- 29580016
TI  - Neurosurgical Management in Anticoagulated Patient: Always a Challenge.

PMID- 29580017
TI  - Unusual Appearance of Trigemino-Cardiac Reflex During Cerebellopontine Angle
      Surgery.

PMID- 29580018
TI  - Letter to the Editor Regarding "Computed Tomography Angiography Spot Sign as an
      Indicator for Ultra-Early Stereotactic Aspiration of Intracerebral Hemorrhage."

PMID- 29580019
TI  - Anterior Transdiskal Screws.

PMID- 29580020
TI  - Ideally, How Early Should Cranioplasty Be Performed-Days, Weeks, or Months
      Following Decompressive Craniectomy Surgery to Label as "Optimal Early
      Cranioplasty"? Big Enigma.

PMID- 29580021
TI  - Letter to the Editor Regarding "World Health Organization Grade II Meningiomas:
      The Role of Adjuvant/Salvage Gamma Knife Surgery After Initial Surgery and
      Prognostic Factor Assessment".

PMID- 29580022
TI  - On the Use of Catheter Angiography for Stereoelectroencephalography Trajectory
      Planning.

PMID- 29580023
TI  - In Reply to the Letter to the Editor "On the Use of Catheter Angiography for
      Stereoelectroencephalography Trajectory Planning".

PMID- 29580024
TI  - Actual Oncologic Impact of Radical Surgical Resection for Malignant Gliomas.

PMID- 29580025
TI  - In Reply to the Letter to the Editor "Actual Oncologic Impact of Radical Surgical
      Resection for Malignant Gliomas".

PMID- 29580026
TI  - Letter to the Editor Regarding "Cisternostomy for Refractory Posttraumatic
      Intracranial Hypertension".

PMID- 29580027
TI  - Less Dogmatic Approach to Severe Traumatic Brain Injury.

PMID- 29580028
TI  - Global Neurosurgery.

PMID- 29580029
TI  - Osteopontin b and c Splice isoforms in Leukemias and SolidTumors: Angiogenesis
      Alongside Chemoresistance
AB  - Osteopontin (OPN) is a glycoprotein involved in regulation of various influences
      on tumor progression, such ascellular proliferation, apoptosis, angiogenesis, and
      metastasis. Vascular endothelial growth factor (VEGF) is a secretedmolecule
      supporting angiogenesis in various cancers through activation of the
      PI3K/AKT/ERK1/2 pathway. OPN andVEGF have a number of isoforms with various
      activities. In spite of the well-defined association between OPN andVEGF isoform
      expression and cure rate for solid tumors, there is a scarcity of information as
      to any association inleukemia. Based on the critical role of OPN in cell
      survival, it seems reasonable to hypothesize that OPN and VEGFisoform expression
      levels may impact on chemoresistance and relapse in leukemia the same as in solid
      tumors. Hence,the aim of our review was to explain relationships between OPN and
      VEGF isoforms and angiogenesis and relatedpathways in chemoresistance of leukemia
      and solid tumors. Our findings demonstrated that OPNb and OPNc alongsidewith VEGF
      isoforms and other gene pathways are involved in angiogenesis and also might
      promote chemoresistanceand even recurrence in leukemia and solid tumors. To sum
      up, targeting OPN isoforms, particularly b and c, might bea novel therapeutic
      strategy for the treatment of leukemia as well as solid tumors.

PMID- 29580030
TI  - Knowledge, Attitudes and Practices Regarding Breast Cancer amongst Lebanese
      Females in Beirut
AB  - Objectives: Regular screening for breast cancer is associated with better
      survival, but compliance with guidelinesdepends on good knowledge and attitudes.
      This study aimed to assess the level of breast cancer knowledge, attitudesand
      screening practices in Lebanese females, and identify their socio-demographic
      determinants as well as barriers tomammography use. Methods: This cross-sectional
      study was conducted with 371 Lebanese females residing in Beirutaged 18-65 with
      no history of breast cancer. The questionnaire applied was adapted from Stager
      and Champion.The overall knowledge score was determined with sections on general
      knowledge, curability, symptoms, and screening;the overall attitude score
      concerned attitudes towards breast cancer, screening, and barriers; and the
      overall practicesscore was for breast self examination (BSE), clinical breast
      examination (CBE) and mammography. Bivariate andmultivariate analyses of
      socioeconomic determinants were performed for each score. Results: The mean
      knowledgescore was 55.5+/-17.1% and that for attitudes was 71.9+/-8.3%. For self
      examination, mammography and clinicalexamination practices, individual means were
      45.7+/-42.3%, 77.9+/-36.5% and 29.1+/-45.5%, respectively. Knowledge,attitudes
      and practices correlated positively with each other (p<0.0001). The highest
      average was the knowledgeof symptoms (72.8+/-24.7%), and the lowest that of
      curability (49.6+/-25.7%). Most frequent barriers to mammographywere fear of
      learning bad news, pain, costs, and staff unpleasantness. Higher education was
      associated with betterknowledge (p=0.002) and smoking with lower levels
      (p=0.003). Older age (p=0.002), higher education (p=0.02),and taking exercise
      (p=0.02) were associated with better attitudes. Higher education (p=0.02) and
      having children(p=0.003) were associated with better practices. Conclusion: More
      emphasis should be placed on educating femaleson the curability of breast cancer
      and specific targeting of the barriers identified.

PMID- 29580031
TI  - Effects of an Educational Program for Prostate Cancer Prevention on knowledge and
      PSA Testing in Men Over 50Years old in Community Areas of Shiraz in 2016
AB  - Background and Objectives: Prostate cancer was reported to be the second cause of
      cancer death in men in 2013.Studies have shown that those with higher knowledge
      levels are much more likely to undergo prostate cancer screening.The present
      study was aimed to determinate the effect of an educational program for prostate
      cancer prevention onknowledge and prostate-specific antigen (PSA) testing in men
      over 50 years old in community areas of Shiraz. Methods:This clinical trial was
      conducted among 93 men over 50 years old who were randomly divided into an
      intervention(n=48) and a control (n=45) group. The intervention group took part
      in an educational program focusing on theimportance of prostate cancer prevention
      with emphasis on cultural and economic issues. Data were collected usinga
      demographic information form, the Weinrich questionnaire for measuring the
      knowledge level about prostate cancerand screening, and also a researcher-made
      questionnaire covering reasons for not doing the test, before and 3 monthsafter
      the intervention. Additionally, participation in PSA testing was evaluated 3
      months after the intervention. All datawere entered into the SPSS statistical
      software (version 14) and p<0.05 was considered to be statistically
      significant.Findings: The results showed that the intervention group's
      participation in PSA testing increased from 6.12% to 36.4%three months after the
      intervention. However, no significant change was observed in the control group.
      In addition,the intervention group's mean score of knowledge increased by about
      2.69 points after the intervention, and a significantdifference was observed
      between the two groups in this regard (p<0.05). Conclusion: The results of the
      current studyrevealed effectiveness of the educational program in increasing the
      knowledge about prostate cancer and participationin PSA testing in men over 50
      years of age. Hence, managers and authorities should execute plans to educate
      menregarding prostate cancer screening and promote their health status.

PMID- 29580032
TI  - Comparative Evaluation of a 6MV Flattened Beam and a Flattening Filter Free Beam
      for Carcinoma of Cervix - IMRTPlanning Study
AB  - Purpose: Intensity modulated radiotherapy (IMRT) plan quality, beam on time and
      integral dose were compared using6MV FB (Flattened Beam) and FFFB (Flattening
      filter free beam) for carcinoma of cervix. Materials and Methods:Ten patients
      with stage II-IIIB cervix cancer (Ca.Cx) were retrospectively identified from the
      department database.Target volume (TV) and organ at risk (OAR) were delineated as
      per Radiation Therapy Oncology Group (RTOG) cancerguidelines. Dose prescribed to
      planning target volume (PTV) was 50.4Gy in 28 fractions. Two plans (6MV FB
      IMRTand 6MV FFFB IMRT) were generated to achieve 95% of prescription dose to PTV
      and sparing OAR as per normaltissue guidelines. Numbers of beams and their
      orientations were the same for all plans. The homogeneity index (HI),conformity
      index (CI), treatment monitor unit (MU), beam on time (BOT) and non-tumor
      integral dose (NTID) werechosen for comparison. Results: FFFB generated plans
      were clinically acceptable. There was a statistically significantdifference among
      the FB IMRT and FFFB IMRT plans with respect to CI, HI, D50%, D2% in PTV
      coverage, bladderV50Gy, MU, mean NTID and non-tumor low dose volume. Conclusions:
      6MV flattened and flattening filter free photonbeams produce comparable plans by
      IMRT . FFF beams allow time efficient treatment delivery and may help reducethe
      risk of secondary malignances in carcinoma cervix cases.

PMID- 29580033
TI  - Evaluation the Anti-Cancer Effect of PEGylated Nano-Niosomal Gingerol, on Breast
      Cancer Cell lines (T47D), In-Vitro
AB  - Background: Cancer is a significant problem in modern medicine, also is the most
      common cause of death aftercardiovascular diseases, and in need of targeted drug
      release. Although, chemotherapy is an important candidate incancer treatment, but
      it has many side effects on healthy tissues of the body. Therefore, Nano
      technology is usedfor specific function, by the least side effects and damage to
      normal cells. Materials and method: In this study, thepharmacological properties
      of PEGylated Nano-niosomal Gingerol was examined. Noisome were prepared using
      reversephase evaporation method, which contains specific proportion of
      cholesterol, span60 and polyethylene glycol. Then,PEGylated the prepared
      formulation by PEG6600. The amount of release and encapsulation of the drug was
      investigated.The percentage of remains of cancer cell line T47D treated with
      PEGylated niosomal Gingerol. Results: The averagediameter of the nanoparticles,
      size distribution and zeta potential were reported for PEGylated niosomal sample
      35.65nm, 0.17 and 21 mv, and for PEGylated niosomal drug sample 256.9 nm, 0.23
      and 28 mv, respectively. The amountof OD for encapsulated drug was 0.198, also
      the amount of concentration of the drug which is not encapsulated, was0.77947 MUl
      of the drug per ml. This value of encapsulated drug was 76.38 percent.
      Conclusion: The results showed thatIC50 of the formulation of PEGylated
      nanoniosomal Gingerol is less than the standard drug. It seems, the cause of
      thisphenomenon is due to the effect of Polyethylene glycol, in more stability and
      slower drug release, in the formulationof PEGylated niosome. Also, Polyethylene
      glycol makes increase in the drug dealing and its greater influence with
      thetarget cell. In this study, more than 76% of the Gingerol drug in PEGylated
      nanoniosomal formulation were enclose.Also, we could reduce the amount of drug
      release, as much as possible.

PMID- 29580034
TI  - Risk Factors, Biomarkers, Etiology, Outcome and Prognosis of Ischemic Stroke in
      Cancer Patients
AB  - Introduction: Cerebrovascular disease is the second most common complication in
      individuals with tumours.The aim of this study was to investigate risk factors,
      biomarkers, etiology and prognosis of ischemic stroke in cancerpatients (ISCPs).
      Methods: The medical records of 619 consecutive patients who were admitted with
      acute ischemicstroke from January 2012 to November 2014 were retrospectively
      evaluated. The patients were divided into two groups(group 1, patients with an
      active cancer prior to the onset of ischemic stroke; group 2, patients without an
      active cancerhistory). The demographic data, risk factors, NIHSS scores,
      thrombocyte count, D-dimer, fibrinogen and C reactiveprotein (CRP) level at
      admission, modified Rankin Scale (mRS) scores in the follow-up period and
      location of lesionson DWI were recorded. The Mann-Whitney U test, chi-squared
      test and logistic regression was used for analyzing data,p<0.05 being considered
      statistically significant. Results: A total of 46 (7.4%) ISCPs were included.
      Hyperlipidemiawas significantly lower in the ISCP group (p=0.001). Elevated
      thrombocyte counts, D-dimer, fibrinogen and CRP levelsat admission, acute
      multiple ischemic lesions, other causes, mortality in hospital and worse outcome
      were significantlyrelated to ISCP (p<0.05). On logistic regression analysis,
      follow up mRS>3, acute multiple ischemic lesions locatedin more than one vascular
      territory (AMIMCT) and other causes were significantly associated with ISCP
      (p<0.001).Conclusion: In our study, other causes, AMIMCT and mRS>3 were more
      common in the ISCP group. We consider thatCCS could be more suitable for
      detecting other causes than TOAST. Biomarkers could be important in the ISCP
      group.

PMID- 29580035
TI  - Fluorescence in Situ Hybridization (FISH) for Differential Diagnosis of Soft
      Tissue Sarcomas
AB  - Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid
      malignancies. The latest editionof WHO soft tissue pathology lists 94 benign and
      malignant soft tissue tumors. Many of these show a large degreeof morphological
      overlap. Immunohistochemistry has been shown to be reliable in many cases for
      differential diagnosisof lesions, although cytogenetic tests are considered the
      gold standard for many entities.Fluorescence in-situ hybridization(FISH) is a
      cytogenetic technique that uses fluorescent probes that bind to only those parts
      of the chromosome whichhave a high degree of sequence complementarity. Many soft
      tissue tumors show recurrent genetic mutations that arenow being used as
      diagnostic markers. Knowledge of the molecular identity allows prediction of
      behavior, prognosisand treatment response. Objective:The aim of this study was to
      identify genetic mutations in soft tissue sarcomas usingFISH testing and to
      assess correlations with histological diagnosis. Material and methods:A total of
      25 cases of differentsoft tissue sarcomas diagnosed on histology with the help of
      immunohistochemical staining and for which FISH studieswere requested were
      included in this study. Three pathologists with a special interest in soft tissue
      sarcomas reviewedthe cases. FISH tests for EWS, the X:18 translocation, FOXO1 and
      MDM2 were respectively applied for 8 cases ofEwing sarcoma, 8 cases of synovial
      sarcoma, 2 cases of rhabdomyosarcoma and 7 cases of dedifferentiated
      liposarcomaand atypical lipomatous tumors/well differentiated liposarcomas.
      Results:EWS gene fusion was detected in 7 out of8 cases of Ewing sarcoma and the
      X:18 translocation was positive in 3 of the 8 cases of synovial sarcoma. FOXO1was
      not detected in either of the two rhabdomyosarcomas. MDM2 by FISH was detected in
      only one out of 5 cases ofatypical lipomatous tumors and 1 out of 2
      dedifferentiated liposarcomas. Conclusion: FISH is a useful adjunct in
      thediagnostic assessment of different types of soft tissue sarcomas. It is easy
      to set up, is relatively inexpensive and hasthe ability to diagnose sarcomas with
      great accuracy, especially in cases which can not be accurately classified
      evenafter thorough histological and immunohistochemical evaluation. It may play a
      very important role in the accuratediagnosis and correct management of patients.

PMID- 29580036
TI  - Clinical implication of hepatic volumetry for living donor liver transplantation.

PMID- 29580037
TI  - Analysis of the Expression of Surface Receptors on NK Cells and NKG2D on
      Immunocytes in Peripheral Blood of Patientswith Nasopharyngeal Carcinoma
AB  - Background: The aberrant expression of surface receptors on immunocytes may
      represent potential markers of tumorescape for nasopharyngeal carcinoma (NPC).
      The aim of this study was to investigate the expression of
      representativereceptors on natural killer (NK) cells and NK group 2, member D
      (NKG2D) on immunocytes in the peripheral bloodof patients with NPC. Methods:
      Patients (n = 64) with NPC prior to initiation of treatment were defined as the
      studygroup. Healthy volunteers (n = 31) served as the control group. The
      expression of NK cells and NKT cells; the triggeringreceptors NKp30, NKp44, and
      NKp46 on NK cells; the activating receptor NKG2D on NK cells, CD4+ T cells,
      andCD8+ T cells; and the inhibitory receptors CD158b and CD159a on NK cells were
      analyzed by flow cytometry in thetwo groups. Results: Here, our study showed that
      no differences were observed in terms of the numbers of NK cells orNKT cells, or
      the expression of CD158b and CD159a on the surface of NK cells between the two
      groups. Nevertheless,the expression levels of NKp30 and NKp46 on NK cells in the
      NPC patients were significantly lower than in the healthyindividuals (P < 0.05).
      No differences existed in the expression of NKG2D on NK cells, but NKG2D on CD8+
      T cellsshowed a markedly lower expression in the study group (P < 0.001).
      Conclusions: Our findings may reflect a possiblemechanism of immune evasion for
      NPC. The enhancement of immunotherapy concerning NKp30, NKp46, and NKG2Dmay be an
      innovative treatment strategy for patients with NPC.

PMID- 29580039
TI  - Impact of Parents and Peers Smoking on Tobacco Consumption Behavior of University
      Students
AB  - Introduction: In the United Arab Emirates, smoking prevalence has increased in
      both sexes, especially amongyoung adults. Various factors have led to this
      catastrophe; examples include coverage on TV and social media, as wellas market
      availability. One major influence is smoking by parents and peers. A lot of
      students may start smoking becauseof the behavior of their family and friends,
      and therefore it is necessary to quantify adverse contributions. The aim ofthis
      project was to study to what degree parents and peers smoking habits may impact
      on smoking behavior of studentsat the University of Sharjah. Methods: This cross
      sectional observational study with a non-probability convenient typeof sampling,
      was conducted with university students aged 18 to 23. Information was collected
      using a self-administeredquestionnaire, comprising 23 questions, developed by
      ourselves. Results: A total of 400 University of Sharjah students(50% males and
      50% females) were included.Some 15.8% of the smoking students had smoking
      parents, and 17.1%of them had smoking peers. The respective figures were 22.2%
      and 21.7% for males and 10% and 7.8% for females.Conclusions: Peers had a
      stronger impact than parents and both parents and peers had greater influence on
      males thanon females. Interestingly, almost 80% of the smoking students did not
      have smoking parents or peers, which leavesthe question unanswered of why they
      started smoking in the first place. Actions at a societal level should be taken
      intoconsideration to prevent smoking and thus help create a non-smoking
      generation.

PMID- 29580038
TI  - Epigenetic Downregulation and Growth Inhibition of IGFBP7 in Gastric Cancer
AB  - Background: Insulin-like growth factor-binding protein 7 (IGFBP7) has been found
      to be a tumor suppressorin several human cancers, but the role of IGFBP7 in
      gastric cancer has not yet been fully investigated. Herein, weexamined the
      epigenetic downregulation of IGFBP7 expression in gastric cancer. Methods:
      Expression and methylationof IGFBP7 in gastric cancer cells and primary gastric
      cancer patients were determined using qRT-PCR, western blot,immunohistochemistry,
      and methylation specific-PCR, respectively. The effects of IGFBP7 on gastric
      cancer cellswere investigated by various experimental conditions, such as
      proliferation, colony formation, apoptosis, invasion,and migration assay.
      Results: IGFBP7 methylation was inversely correlated with IGFBP7 expression in
      gastriccancer. Univariate and multivariate analysis showed that IGFBP7 expression
      and tumor stage were independentprognostic factors. IGFBP7 knockdown increased
      gastric cancer cell growth, invasion, and migration, whereas IGFBP7overexpression
      in gastric cancer cells induced cell growth inhibition and apoptosis. Conclusion:
      Our data suggest thatIGFBP7 functions as a tumor suppressor in gastric cancer via
      an epigenetic pathway.

PMID- 29580040
TI  - Adverse Effects of Vincristine Chemotherapy on Cell Changes in Seminiferous
      Tubules and Cetrorelix GnRH AntagonistInhibitory Effects in Mice
AB  - The present study was designed to determine changes in spermatogenesis in adult
      mice after an intraperitoneal injectionof vincristine. The effect of a GnRH
      antagonist synchronous to chemotherapy, which might protect spermatogenesisby
      halting cell division in spermatogenic cells, was also investigated. Method and
      Materials: A total of 30 adult malemice were studied in three equal groups of
      ten. In the V group, a single dose of the chemotherapy drug vincristine
      wasinjected intraperitonally at 1.5 mg/kg. In the V+C, group, the injection of
      Cetrorelix was started, and one week beforeto one week after vincristine
      injection continued ( for 3 weeks). Controls received no treatment. Samples were
      takenfrom the testicles, and fixed in Boueins fixative for light microscopy.
      Results: Comparing the mean number of Sertoliand spermatogony cells and the rate
      of spermatogenesis index (SI) in the V group with controls showed
      significantdifferences,which were not evident in the V+C group. Conclusion:
      According to the results, the cetrorelix antagonist(GnRH) could largely prevent
      side effects of vincristine administration regarding seminiferous tubules.

PMID- 29580041
TI  - Galectin-3 Serum Levels Could Help Clinicians Screen for Salivary Gland Tumor
      Patients
AB  - Objective: To identify serum levels of galectin-3 in salivary gland cancer and
      healthy populations; a prospectiveanalysis was performed on serum specimens from
      105 patients with salivary gland cancer and 56 healthy persons.Methods: Enzyme
      linked immunosorbent assay (ELISA) was used to measure levels of galectin-3 (GAL
      3). Serumlevels were compared between patients with salivary gland tumors and
      healthy control. A total of 105 patients wereenrolled in the study (55 men, 50
      women). Result: Mean age was 45.5 years. Thirty-nine patients with malignant
      and66 cases with benign tumors were compared with 56 healthy participants with a
      mean age of 51.7. No statisticallysignificant differences were observed when
      comparing GAL-3 serum levels between malignant and benign salivary glandtumor
      patients, but a statistically significant difference was found between case and
      control patients with p-values of0.02. Serum levels of galectin-3 protein were
      elevated in patients with salivary gland cancer compared with the
      healthypopulation. Conclusion: The difference between benign and malignant tumor
      patients was significant, but revealedno clinic pathological characteristics in
      malignant tumors. To the best of the authors' knowledge, this is the first timea
      study suggests that GAL-3 serum levels could help clinicians screen for salivary
      gland cancer.

PMID- 29580042
TI  - Associations of ICOS and PD.1 Gene Variants with Colon Cancer Risk in The Iranian
      Population
AB  - Background: Positive and negative co-stimulatory molecules are important factors
      determining the outcomeof immune responses to the presence of tumors. Since co
      stimulatory molecule expression may be affected by genepolymorphisms, we aimed to
      investigate associations between variants of PD.1 and ICOS and susceptibility to
      coloncancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (
      538G/A) gene polymorphisms wereevaluated by the PCR-RFLP method in 76 colon
      cancer patients and 73 healthy controls. Results: The frequenciesof the GG
      genotype and the G allele at position -693 of the ICOS gene were significantly
      higher in the patient group(P=0.014 and p=0.0002), while the AA genotype was
      significantly more common in controls (P=0.0016). At position-538 of PD.1, GG
      genotype and G allele frequencies were higher in the patient group (P<0.0001and
      P<0.0001). Again,AA and also AG genotypes significantly predominated in controls
      (P<0.0001 and P=0.012). Regarding genotypesand alleles of ICOS at position +1720.
      Frequencies of GCG and GTG haplotypes were higher in patients comparedto those of
      controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG
      haplotypes were higher incontrols (P=0.0017, P<0.0001 and P=0.015). GTG/GTG and
      GTG/GCG double haplotypes were more frequent inpatients compared to controls
      (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A)
      andICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors
      for the development of colon canceramong Iranian patients.

PMID- 29580043
TI  - Prostate Specific Antigen, Mean Platelet Volume, and Platelet Distribution Width
      in Combination to Discriminate ProstateCancer from Benign Prostate Hyperplasia
AB  - Background: Prostate cancer (PCa) represents the second most commonly diagnosed
      malignancy and the sixthleading cause for cancer related death among men
      worldwide. Although use of the prostate specific antigen (PSA) asa diagnostic
      marker has improved the detection and management of PCa, low specificity and
      sensitivity has limited itsclinical efficacy. Moreover, elevated PSA is
      frequently observed in benign prostate hyperplasia (BPH). Mean plateletvolume
      (MPV) and platelet distribution width (PDW) are commonly used indicators of
      platelet activation. The purposeof current study was to investigate the ability
      of PSA, MPV, and PDW individually or in combination, to differentiatePCa from
      BPH. Materials and Methods: This study included 100 patients with PCa and 108
      patients with BPH. Wecollected all participants' clinical and laboratory
      characteristics. The benefit of adding MPV and PDW to a modelwith only PSA was
      evaluated as an increased in the area under the curve (AUC) obtained by receiver
      operating curve(ROC). Results: PCa patients had reduced MPV and elevated PSA and
      PDW levels compared to BPH patients. Singlebiomarkers had AUC values ranging from
      0.683 for PDW to 0.865 for PSA. Moreover, the combination of PSA, MPV,and PDW
      increased the AUC to 0.935 (0.892-0.964) (p<0.0001), significantly higher than
      those of any single marker.Conclusions: The combined use of PSA, MPV, and PDW may
      be clinically useful in distinguishing between PCa andBPH.

PMID- 29580044
TI  - Alcohol Consumption as a Risk Factor for Breast Cancer Development: A Case
      Control Study in Brazil
AB  - Background: Alcohol consumption is a well-established risk factor for breast
      cancer, but the evidence is mostlyfrom developed countries. Brazil is going
      through a rapid demographic expansion, and studies of this relationship arealso
      needed in such unexplored settings. Methods: We assessed the relationship between
      alcohol consumption andbreast cancer risk among 1,506 Brazilian women (406 cases
      and 1,100 controls). Regression models were used tocalculate odds ratios (OR) and
      95% confidence intervals (CI). All statistical tests were two-tailed. Results:
      The meanage of the 1,506 women was 42.0 (standard deviation, +/-15.0) years.
      There was a significant association between breastcancer and age, body mass
      index, age at menarche, menstrual flow and menstrual cycle. Multivariate analysis
      showedan increased risk of invasive breast cancer in regular alcohol consumers
      (<50 years old: OR 4.7; 95% CI 1.4-16.2; >=50years old: OR 3.9; 95% CI 1.2-13.4)
      compared with abstainers or occasional drinkers. Women with a regular
      alcoholintake for 10 years or more who were less than 50 years old had a
      threefold higher risk of developing breast cancer(OR 3.0; 95% CI 1.2-7.6).
      Conclusion: Regular alcohol consumption increases the risk of breast cancer
      mainly amongwomen less than 50 years old.

PMID- 29580045
TI  - Thirty Years Cancer Incidence Data for Lahore, Pakistan: Trends and Patterns 1984
      2014
AB  - This research was conducted to generate trends and patterns of most common male
      and female cancers from1984-2014 for the city population of Lahore Pakistan.
      Cancer incidence data gathered for different organs wereprocessed through
      cleaning, integration, transformation, reduction and mining for ultimate
      representation. Risk ofcancer appeared to be continuously increasing among both
      males and females. Overall, lymphomas and breast cancerare the most common
      neoplasm in males and females, respectively, in Lahore with almost the highest
      rates in the AsianPacific region. The incidence of head and neck, brain, and lung
      cancers, as well as leukemia have rapidly increasedamong males, whereas, ovarian,
      cervix, head and neck and lymphomas have become more common among females.The
      present communication should be helpful for adequate strategic planning,
      identification of risk factors and takingappropriate prevention and control
      measures at the national level.

PMID- 29580046
TI  - Initial clinical outcomes of proton beam radiotherapy for hepatocellular
      carcinoma.
AB  - PURPOSE: This study aimed to evaluate the initial outcomes of proton beam therapy
      (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety.
      MATERIALS AND METHODS: HCC patients who were not indicated for standard curative
      local modalities and who were treated with PBT at Samsung Medical Center from
      January 2016 to February 2017 were enrolled. Toxicity was scored using the Common
      Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was
      evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST).
      RESULTS: A total of 101 HCC patients treated with PBT were included. Patients
      were treated with an equivalent dose of 62-92 GyE10. Liver function status was
      not significantly affected after PBT. Greater than 80% of patients had Child-Pugh
      class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78
      patients followed for three months after PBT, infield complete and partial
      responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively.
      CONCLUSION: PBT treatment of HCC patients showed a favorable infield complete
      response rate of 69.2% with acceptable acute toxicity. An additional follow-up
      study of these patients will be conducted.

PMID- 29580047
TI  - The feasibility of shear wave elastography for diagnosing superficial benign soft
      tissue masses.
AB  - Purpose: The purpose of this study was to investigate the feasibility of shear
      wave ultrasound elastography for differentiating superficial benign soft tissue
      masses through a comparison of their shear moduli. Methods: We retrospectively
      analyzed 48 masses from 46 patients from February 2014 to May 2016. Surgical
      excision, fine-needle aspiration, and clinical findings were used for the
      differential diagnosis. The ultrasonographic examinations were conducted by a
      single musculoskeletal radiologist, and the ultrasonographic findings were
      reviewed by two other radiologists who were blinded to the final diagnosis.
      Conventional ultrasonographic features and the median shear modulus were
      evaluated. We compared the median shear moduli of epidermoid cysts, ganglion
      cysts, and lipomatous tumors using the Kruskal-Wallis test. Additionally, the
      Mann-Whitney U test was used to compare two distinct groups. Results: Significant
      differences were found in the median shear moduli of epidermoid cysts, ganglion
      cysts, and lipomatous tumors (23.7, 5.8, and 9.2 kPa, respectively, P=0.019).
      Epidermoid cysts showed a greater median shear modulus than ganglion cysts
      (P=0.014) and lipomatous tumors (P=0.049). Conclusion: Shear wave elastography
      may contribute to the differential diagnosis of superficial benign soft tissue
      masses through a direct quantitative analysis.

PMID- 29580048
TI  - Elucidating Environmental Fingerprinting Mechanisms of Unconventional Gas
      Development through Hydrocarbon Analysis.
AB  - Hydraulic fracturing is an increasingly common technique for the extraction of
      natural gas entrapped in shale formations. This technique has been highly
      criticized due to the possibility of environmental contamination, underscoring
      the need for method development to identify chemical factors that could be
      utilized in point-source identification of environmental contamination events.
      Here, we utilize comprehensive two-dimensional gas chromatography (GC * GC)
      coupled to high-resolution time-of-flight (HRT) mass spectrometry, which offers a
      unique instrumental combination allowing for petroleomics hydrocarbon
      fingerprinting. Four flowback fluids from Marcellus shale gas wells in geographic
      proximity were analyzed for differentiating factors that could be exploited in
      environmental forensics investigations of shale gas impacts. Kendrick mass defect
      (KMD) plots of these flowback fluids illustrated well-to-well differences in
      heteroatomic substituted hydrocarbons, while GC * GC separations showed variance
      in cyclic hydrocarbons and polyaromatic hydrocarbons among the four wells.
      Additionally, generating plots that combine GC * GC separation with KMD
      established a novel data-rich visualization technique that further differentiated
      the samples.

PMID- 29580049
TI  - First-Principles Integrated Adsorption Modeling for Selective Capture of Uranium
      from Seawater by Polyamidoxime Sorbent Materials.
AB  - Nuclear power is a relatively carbon-free energy source that has the capacity to
      be utilized today in an effort to stem the tides of global warming. The growing
      demand for nuclear energy, however, could put significant strain on our uranium
      ore resources, and the mining activities utilized to extract that ore can leave
      behind long-term environmental damage. A potential solution to enhance the supply
      of uranium fuel is to recover uranium from seawater using amidoximated adsorbent
      fibers. This technology has been studied for decades but is currently plagued by
      the material's relatively poor selectivity of uranium over its main competitor
      vanadium. In this work, we investigate the binding schemes between uranium,
      vanadium, and the amidoxime functional groups on the adsorbent surface. Using
      quantum chemical methods, binding strengths are approximated for a set of
      complexation reactions between uranium and vanadium with amidoxime
      functionalities. Those approximations are then coupled with a comprehensive
      aqueous adsorption model developed in this work to simulate the adsorption of
      uranium and vanadium under laboratory conditions. Experimental adsorption studies
      with uranium and vanadium over a wide pH range are performed, and the data
      collected are compared against simulation results to validate the model. It was
      found that coupling ab initio calculations with process level adsorption modeling
      provides accurate predictions of the adsorption capacity and selectivity of the
      sorbent materials. Furthermore, this work demonstrates that this multiscale
      modeling paradigm could be utilized to aid in the selection of superior ligands
      or ligand compositions for the selective capture of metal ions. Therefore, this
      first-principles integrated modeling approach opens the door to the in silico
      design of next-generation adsorbents with potentially superior efficiency and
      selectivity for uranium over vanadium in seawater.

PMID- 29580050
TI  - Indirect X-ray Detectors Based on Inkjet-Printed Photodetectors with a Screen
      Printed Scintillator Layer.
AB  - Organic photodetectors (PDs) based on printing technologies will allow to expand
      the current field of PD applications toward large-area and flexible applications
      in areas such as medical imaging, security, and quality control, among others.
      Inkjet printing is a powerful digital tool for the deposition of smart and
      functional materials on various substrates, allowing the development of
      electronic devices such as PDs on various substrates. In this work, inkjet
      printed PD arrays, based on the organic thin-film transistor architecture, have
      been developed and applied for the indirect detection of X-ray radiation using a
      scintillator ink as an X-ray absorber. The >90% increase of the photocurrent of
      the PDs under X-ray radiation, from about 53 nA without the scintillator film to
      about 102 nA with the scintillator located on top of the PD, proves the
      suitability of the developed printed device for X-ray detection applications.

PMID- 29580051
TI  - General Theory of Absorption in Porous Materials: Restricted Multilayer Theory.
AB  - In this article, we present an approach for the generalization of adsorption of
      light gases in porous materials. This new theory goes beyond Langmuir and
      Brunauer-Emmett-Teller theories, which are the standard approaches that have a
      limited application to crystalline porous materials by their unphysical
      assumptions on the amount of possible adsorption layers. The derivation of a more
      general equation for any crystalline porous framework is presented, restricted
      multilayer theory. Our approach allows the determination of gas uptake
      considering only geometrical constraints of the porous framework and the
      interaction energy of the guest molecule with the framework. On the basis of this
      theory, we calculated optimal values for the adsorption enthalpy at different
      temperatures and pressures. We also present the use of this theory to determine
      the optimal linker length for a topologically equivalent framework series. We
      validate this theoretical approach by applying it to metal-organic frameworks
      (MOFs) and show that it reproduces the experimental results for seven different
      reported materials. We obtained the universal equation for the optimal linker
      length, given the topology of a porous framework. This work applied the general
      equation to MOFs and H2 to create energy-storage materials; however, this theory
      can be applied to other crystalline porous materials and light gases, which opens
      the possibility of designing the next generations of energy-storage materials by
      first considering only the geometrical constraints of the porous materials.

PMID- 29580052
TI  - High Selectivity Toward C2H4 Production over Cu Particles Supported by Butterfly
      Wing-Derived Carbon Frameworks.
AB  - Converting carbon dioxide to useful C2 chemicals in a selective and efficient
      manner remains a major challenge in renewable and sustainable energy research.
      Herein, we adopt butterfly wings to assist the preparation of an electrocatalyst
      containing monodispersed Cu particles supported by nitrogen-doped carbon
      frameworks for an efficient reduction of CO2. Benefiting from structure
      advantages and the synergistic effect between nitrogen dopants and stepped
      surface-rich Cu particles, the resulting catalyst exhibited a high faradic
      efficiency of 63.7 +/- 1.4% for ethylene production (corresponding to an
      ethylene/methane products' ratio of 57.9 +/- 5.4) and an excellent durability
      (~100% retention after 24 h). This work presents some guidelines for the rational
      design and accurate modulation of metal heterocatalysts for high selectivity
      toward ethylene from CO2 electroreduction.

PMID- 29580053
TI  - Occurrence of Glucocorticoids, Mineralocorticoids, and Progestogens in Various
      Treated Wastewater, Rivers, and Streams.
AB  - In the current study a high sensitive analytical method was developed for the
      determination of 60 steroids including glucocorticoids (GC), mineralocorticoids
      (MC), and progestogens (PG) in WWTP effluents and surface water using liquid
      chromatography with tandem mass spectrometry detection (LC-MS/MS). The limits of
      quantification (LOQ) ranged between 0.02 ng/L (cortisone) to 0.5 ng/L
      (drospirenone) in surface water and from 0.05 ng/L (betamethasone) to 5 ng/L
      (chlormadinone) in treated wastewater. After optimization, the developed method
      was applied to WWTP effluents, rivers, and streams around Germany. Numerous
      steroids have been detected during the sampling campaign and predominant analytes
      from all steroid types were determined. Moreover, the occurrence of dienogest,
      mometasone furoate, flumethasone pivalate, and the metabolites 6beta-hydroxy
      dienogest, 6beta-hydroxy triamcinolone acetonide, 7alpha-thiomethyl
      spironolactone, and 11alpha-hydroxy canrenone is reported for the first time. In
      addition, this study revealed the ubiquitous presence of topically applied GC
      monoesters betamethasone propionate, betamethasone valerate, and 6alpha
      methylprednisolone propionate in WWTP effluents and surface water.

PMID- 29580054
TI  - Efficient Bifacial Semitransparent Perovskite Solar Cells Using Ag/V2O5 as
      Transparent Anodes.
AB  - Bifacial semitransparent inverted planar structured perovskite solar cells (PSCs)
      based on Cs0.05FA0.3MA0.7PbI2.51Br0.54 using an Ag thin film electrode and V2O5
      optical coupling layer are investigated theoretically and experimentally. It is
      shown that the introduction of the cesium (Cs) ions in the perovskite could
      obviously improve the device performance and stability. When only the bare Ag
      film electrode is used, the PSCs show a bifacial performance with the power
      conversion efficiency (PCE) of 14.62% illuminated from the indium tin oxide (ITO)
      side and 5.45% from the Ag film side. By introducing a V2O5 optical coupling
      layer, the PCE is enhanced to 8.91% illuminated from the Ag film side, which is
      63% improvement compared with the bare Ag film electrode, whereas the PCE
      illuminated from the ITO side remains almost unchanged. Moreover, when a back
      reflector is employed, the PCE of device could be further improved to 15.39% by
      illumination from the ITO side and 12.44% by illumination from the Ag side. The
      devices also show superior semitransparent properties and exhibit negligible
      photocurrent hysteresis, irrespective of the side from which the light is
      illuminated. In short, the Ag/V2O5 double layer is a promising semitransparent
      electrode due to its low cost and simple preparation process, which also point to
      a new direction for the bifacial PSCs and tandem solar cells.

PMID- 29580056
TI  - Study of the Gemini Surfactants' Self-Assembly on Graphene Nanosheets: Insights
      from Molecular Dynamic Simulation.
AB  - Understanding the mechanism of adsorption and self-assembly of surfactants on
      graphene is highly important to perform better optimization of the graphene
      dispersion process. Because of Gemini surfactants' special structure, they have a
      high charge capacity, high hydrophobicity, and unique self-assembly properties
      compared to single-chain surfactants. Therefore, Gemini surfactants with their
      small concentrations are expected to disperse and stabilize graphene nanosheets
      in aqueous solutions more effectively. We conducted molecular dynamics
      simulations to study adsorption and self-assembly of single-chain cationic
      surfactant dodecyltrimethylammonium bromide (C12TAB) and its same family Gemini
      surfactant dimethylene-alpha,beta-bis(dodecyldimethylammonium bromide) ([12-2
      12]Br2) on graphene nanosheets. The results showed that assemblies morphology
      formed on graphene is affected by surfactant structure. We observed that
      increasing surface coverage, especially for [12-2-12]Br2, leads to a transmission
      in adsorption mechanism and most [12-2-12]Br2 head groups tend toward the aqueous
      phase and prevent water molecules from accessing graphene surface. It can be
      concluded from morphological assessments that [12-2-12]Br2 is more effective than
      C12TAB in stabilizing graphene aqueous suspensions. Moreover, we investigated the
      effect of graphene sheet size and Gemini surfactant spacer length on the
      structure of surfactant assemblies on graphene. The present study results can
      expand our comprehension of dispersion mechanism of graphene nanosheets by Gemini
      surfactants.

PMID- 29580055
TI  - Gate-Induced Metal-Insulator Transition in MoS2 by Solid Superionic Conductor
      LaF3.
AB  - Electric-double-layer (EDL) gating with liquid electrolyte has been a powerful
      tool widely used to explore emerging interfacial electronic phenomena. Due to the
      large EDL capacitance, a high carrier density up to 1014 cm-2 can be induced,
      directly leading to the realization of field-induced insulator to metal (or
      superconductor) transition. However, the liquid nature of the electrolyte has
      created technical issues including possible side electrochemical reactions or
      intercalation, and the potential for huge strain at the interface during cooling.
      In addition, the liquid coverage of active devices also makes many surface
      characterizations and in situ measurements challenging. Here, we demonstrate an
      all solid-state EDL device based on a solid superionic conductor LaF3, which can
      be used as both a substrate and a fluorine ionic gate dielectric to achieve a
      wide tunability of carrier density without the issues of strain or
      electrochemical reactions and can expose the active device surface for external
      access. Based on LaF3 EDL transistors (EDLTs), we observe the metal-insulator
      transition in MoS2. Interestingly, the well-defined crystal lattice provides a
      more uniform potential distribution in the substrate, resulting in less interface
      electron scattering and therefore a higher mobility in MoS2 transistors. This
      result shows the powerful gating capability of LaF3 solid electrolyte for new
      possibilities of novel interfacial electronic phenomena.

PMID- 29580057
TI  - Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging beta
      Amyloid in Alzheimer's Disease Affected Brain.
AB  - In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2-
      a]pyridine derivatives and examine their suitability as novel probes for single
      photon emission computed tomography (SPECT)-based imaging of beta-amyloid
      (Abeta). Among the 11 evaluated compounds, 10 showed moderate affinity to Abeta(1
      42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7
      +/- 6.07-87.6 +/- 39.8 nM. In vitro autoradiography indicated that 123I-labeled
      triazole-substituted derivatives displayed highly selective binding to Abeta
      plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain.
      Moreover, biodistribution studies performed on normal rats demonstrated that all
      123I-labeled probes featured high initial uptake into the brain followed by a
      rapid washout and were thus well suited for imaging Abeta plaques, with the
      highest selectivity observed for a 1 H-1,2,3-triazole-substituted 2-pyridyl
      imidazopyridine derivative, [123I]ABC577. This compound showed good kinetics in
      rat brain as well as moderate in vivo stability in rats and is thus a promising
      SPECT imaging probe for AD in clinical settings.

PMID- 29580058
TI  - Influence of High pH on the Organization of Acetonitrile at the Silica/Water
      Interface Studied by Sum Frequency Generation Spectroscopy.
AB  - The acetonitrile-water mixture is one of the most commonly used solvents in
      hydrophilic interaction chromatography, which contains silica as the solid phase.
      As such, the silica/acetonitrile-water interface plays a large role in the
      separation of compounds. Varying the pH is one way to influence retention times,
      particularly of ionizable solutes, yet the influence of high pH is often
      unpredictable. To determine how the structure of this interface changes with pH,
      we utilized the surface specific technique sum frequency generation (SFG).
      Previous SFG studies at neutral pH have suggested the existence of acetonitrile
      bilayers at the aqueous silica interface even at low acetonitrile mole fractions.
      Here we find that the SFG signal from 2900 to 3040 cm-1 at the
      silica/acetonitrile-water interface increased as we adjusted the aqueous pH from
      near neutral to high values. This increase in signal was attributed to a greater
      amount of aligned water which is consistent with an increase in silica surface
      charge at high pH. In contrast, complementary measurements of the
      silica/acetonitrile-deuterium oxide interface revealed that the acetonitrile
      methyl mode nearly vanished as the aqueous pH was increased. This loss of methyl
      mode signal is indicative of a decrease in the number density of acetonitrile
      molecules at the interface, as orientation analysis indicates no significant
      change in the net orientation of the outer leaflet of the acetonitrile bilayer
      over the pH range studied.

PMID- 29580059
TI  - Adsorbed Layer Thickness Determination for Convective-Based Media from Pressure
      Drop Data.
AB  - In the present work, we derive a theoretical framework to determine the adsorbed
      layer thickness from pressure drop measurements for convective-based media
      without any assumptions about the geometry of the pore structure of the
      stationary phase matrix. Equations are presented to calculate accuracy of the
      estimated adsorbed layer thickness as a consequence of measurement error and
      approximations of the mathematical model. We discovered that there is a minimum
      in the error for certain pressure drops that results in optimal experimental
      conditions for determining the adsorbed layer thickness. We demonstrate that the
      adsorbed layer thickness can be determined with less than 10% error using a wide
      range of experimental conditions simply from pressure drop data. By careful
      selection of porous bed dimensions and flow rates, the adsorbed layer thicknesses
      from subnanometer dimensions up to several hundred nanometers can be determined
      by measurement of the pressure drop in a range of several bars. The method was
      experimentally tested on methacrylate monolithic columns using monodisperse latex
      nanoparticles as a reference standard and two different proteins as unknowns
      demonstrating close agreement with calculations.

PMID- 29580060
TI  - In Nano, Volume 12, Issue 3.

PMID- 29580061
TI  - Energy Storage in Nanomaterials - Capacitive, Pseudocapacitive, or Battery-like?

PMID- 29580062
TI  - Service user preferences for diabetes education in remote and rural areas of the
      Highlands and Islands of Scotland.
AB  - INTRODUCTION: Diabetes prevalence in Scotland is 5.3%, with type 2 diabetes
      accounting for 86.7% of all cases in the National Health Service Highlands health
      board area and 85.7% in the Western Isles. Structured education is a key
      component in the management of this chronic disease. However, current group
      session models are less feasible in lower-population non-urban environments due
      to distance, participant numbers and access to appropriately trained healthcare
      professionals. Group sessions may also be a less attractive option in small
      communities, where people tend to have close day-to-day personal contact. This
      study assesses the access and delivery preferences of remote and rural service
      users in the Highlands and Western Isles to structured diabetes education
      programs. METHODS: The study used a mixed methods approach of focus groups and
      questionnaires with people with type 2 diabetes in the Highlands and Islands of
      Scotland. Both modes of participation were designed to explore perception of
      diabetes knowledge, diabetes education and use of technology. RESULTS: One-to-one
      delivery was the delivery method of choice; however, there was a preference for a
      digital approach over group education sessions. Service users expressed a strong
      desire to be able to learn at their own pace, when and where they wanted to, and
      with no requirement to travel. To address these requirements an online resource,
      providing access to both learning sessions and trusted sources of information,
      was the preferred mode of delivery. CONCLUSIONS: People with type 2 diabetes
      living in remote and rural areas of the Scottish Highlands and Islands who
      already use the internet are receptive to the use of digital technology for
      delivery of diabetes education and are interested in learning more about
      management of their condition through this medium. They believe that a technology
      approach will provide them with more control over the pace of learning, and where
      and when this learning can take place.

PMID- 29580063
TI  - Ambient air pollution and cardiovascular diseases: From bench to bedside.
AB  - Air pollution has a great impact on health, representing one of the leading
      causes of death worldwide. Previous experimental and epidemiological studies
      suggested the role of pollutants as risk factors for cardiovascular diseases. For
      this reason, international guidelines included specific statements regarding the
      contribution of particulate matter exposure to increase the risk of these events.
      In this review, we summarise the main evidence concerning the mechanisms involved
      in the processes linking air pollutants to the development of cardiovascular
      diseases.

PMID- 29580064
TI  - Digest April 2018

PMID- 29580065
TI  - Status of Rifaximin: A Review of Characteristics, Uses and Analytical Methods.
AB  - Rifaximin, an oral antimicrobial, has many advantages because it is selective
      intestine, has minimal adverse effects and is used for the treatment of some
      diseases such as hepatic encephalopathy, irritable bowel syndrome, travelers'
      diarrhea, ulcerative colitis, Clostridium difficile and acute diarrhea. Rifaximin
      in the form of 200 mg tablets is commercially available. The crystalline alpha
      form is therapeutically safe and effective. In most of the official compendia,
      rifaximin has no monograph and in none of them is there a monograph for rifaximin
      tablets. The literature, however, contemplates this gap with varied methods. The
      literature presents some methods for evaluation of rifaximin in both biological
      fluid and pharmaceutical product. High performance liquid chromatography stands
      out for the evaluation of rifaximin. Most of the methods reported in the
      literature are for pharmaceuticals products. They use (1) toxic organic solvents,
      harmful to the operator and the environment, and/or (2) buffer solution, which
      has a shorter service life and requires time-consuming washes of the
      chromatographic system generating more waste. So, this work aims to discuss (i)
      properties; (ii) applications; (iii) polymorphism and (iv) analytical methods of
      rifaximin by the look of green chemistry. This review shows an extremely current
      topic of great importance to the chemical-pharmaceutical area and everything it
      involves, since the analytical process until the impact on the environment in
      which it is embedded.

PMID- 29580066
TI  - Application of edible coating with essential oil in food preservation.
AB  - Compared with other types of packaging, edible coatings are becoming more and
      more popular because of their more environmentally friendly properties and active
      ingredients carrying ability. The edible coating can reduce the influence of
      essential oils (EOs) on the flavor of the product and also can prolong the action
      time of EOs through the slow-release effect, which effectively promote the
      application of EOs in food. Understanding the different combinations of edible
      coatings and EOs as well as their antimicrobial effects on different
      microorganisms will be more powerful and targeted to promote the application of
      EOs in real food systems. The review focus on the contribution of the combination
      of EOs and edible coatings (EO-edible coatings) to prolong the shelf life of food
      products, (1) specifically addressing the main materials used in the preparation
      of EO-edible coatings and the application of EO-edible coatings in the product,
      (2) systematically summarizing the main production method of EO-edible coatings,
      (3) discussing the antiseptic activity of EO-edible coatings on different
      microorganisms in food.

PMID- 29580067
TI  - Migraine is common in patients with sarcoidosis.
AB  - OBJECTIVE: To describe the frequency of migraine and predictors of having
      migraine in sarcoidosis patients. METHODS: The ID migraine questionnaire was
      administered to a well-phenotyped observational cohort of sarcoidosis patients
      (most of whom were seeking specialty care) and healthy controls. Predictors of
      migraine status were examined using univariate and multivariable logistic
      regression. RESULTS: Migraine was seen in 29% of 96 patients with sarcoidosis and
      13% of 39 healthy controls, ( p = 0.049). Among those with sarcoidosis, in
      univariate regression analysis only female sex was predictive of having migraine,
      and in a multivariable regression female sex remained significant (OR 4.6, 95% CI
      1.2-18.2). There was no association between migraine and age, depression,
      dyspnea, immunosuppression use, or ESR. CONCLUSIONS: Migraine is a common
      comorbidity in sarcoidosis patients. As such, better recognition and targeted
      treatment of migraine has the potential to improve quality of life as part of a
      comprehensive care plan for sarcoidosis patients.

PMID- 29580069
TI  - Is a rapid increase in nitrogen oxides really associated with an acute myocardial
      infarction?

PMID- 29580068
TI  - Gut interpretations: how difficulties in emotion regulation may help explain the
      relation of visceral sensitivity with depression and anxiety among young adults
      with gastrointestinal symptoms.
AB  - It is widely recognized that abdominal pain and discomfort are common problems in
      the United States and are often associated with negative quality of life. The
      prevalence of anxiety/depression elevations and disorders among persons with
      gastrointestinal disturbances (GI) is estimated to be at least two to three times
      the rate in the general population. Visceral sensitivity reflects anxiety about
      GI sensations and its accompanying contexts and often leads to worsening of
      sensations (e.g. bloating, upset stomach, diarrhea). Among individuals with GI
      symptoms, visceral sensitivity may be associated with interpreting common
      sensations as catastrophic which may be related to greater difficulties with
      emotion dysregulation (e.g. severe anxiety and depression). The current study
      evaluated the indirect association of visceral sensitivity via emotion
      dysregulation in relation to depression, anxious arousal, and social anxiety
      symptoms among 344 young adults with a current history of GI symptoms and
      problems. Results indicated an indirect effect of visceral sensitivity via
      emotion dysregulation. These findings provide novel empirical support for the
      association of visceral sensitivity with emotional distress symptoms among young
      adults with GI symptoms. Based on the results, targeting emotion dysregulation
      may be a promising health promotion tactic among young adults with GI symptoms
      and disorders.

PMID- 29580070
TI  - Circadian gene methylation profiles are associated with obesity, metabolic
      disturbances and carbohydrate intake.
AB  - The circadian clock regulates the daily rhythms of several physiological and
      behavioral processes. Disruptions in clock genes have been associated with
      obesity and related comorbidities. This study aimed to analyze the association of
      DNA methylation signatures at circadian rhythm pathway genes with body mass index
      (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was
      determined by microarray in white blood cells from 474 adults from the Methyl
      Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and
      Genomes database was used to identify the genes integrating the circadian rhythm
      pathway. Network enrichment analyses were performed with the PathDIP platform.
      Associations between circadian methylation patterns with anthropometric
      measurements, the metabolic profile, clinical data and dietary intakes were
      analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm
      pathway genes were strongly correlated with BMI (false discovery rates <0.0001).
      These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3),
      cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1),
      cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment
      analyses revealed that the six BMI-associated genes statistically contributed to
      the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition,
      methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628
      (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p <
      0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant
      correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628
      (BHLHE40) with total energy and carbohydrate intakes were found. This
      investigation revealed potential associations of DNA methylation profiles at
      circadian genes with obesity, metabolic disturbances and carbohydrate intake,
      with potential impact on weight homeostasis.

PMID- 29580071
TI  - Metabolic syndrome components: Is there a difference according to exposure to
      night work?
AB  - The aim of this study was to compare metabolic aspects potentially associated
      with metabolic syndrome (MetS), in addition to serum leptin levels and sleep,
      according to exposure to night work among nursing staff. A cross-sectional study
      involving 60 nursing staff was conducted. Sociodemographic, sleep (Karolinska
      Sleep Questionnaire), physical activity (International Physical Activity
      Questionnaire), and nutrition data (16-Food Intake Questionnaire) were collected.
      Body measurements and blood pressure were taken and blood collected to determine
      glycemia, total cholesterol and portions of low-density lipoprotein and high
      density lipoprotein and triglycerides, and leptin levels. The sample was divided
      into three groups according to exposure to night work (nonexposed, currently
      exposed, past exposure). Furthermore, to evaluate the relationship between
      exposure time and prevalence of MetS, the night-exposed groups (past and current)
      were divided according to time exposed to night shifts (<10 years and >=10
      years). Mean age of participants was 39.8 +/- 10.5 years. The groups were
      homogenous with regard to sociodemographic characteristics, physical activity,
      dietary patterns, and health aspects. The prevalence of MetS in the population
      studied was 32%, above the rate for the general population. However, there were
      no significant differences among the groups. In addition, a higher proportion of
      participants with hypertriglyceridemia and diastolic arterial hypertension was
      observed in the currently exposed group. The currently exposed group also
      reported less sleep and higher sleep debt than the other groups on workdays.
      Although no differences were observed among the groups regarding MetS, the
      currently exposed group had more sleep disturbances than the others, and a higher
      prevalence of two out of three risk factors for the MetS diagnosis.

PMID- 29580072
TI  - Bright light exposure before bedtime impairs response inhibition the following
      morning: a non-randomized crossover study.
AB  - INTRODUCTION: Bright light exposure in the late evening can affect cognitive
      function the following morning either by changing the biological clock and/or
      disturbing sleep, but the evidence for this effect is scarce, and the underlying
      mechanism remains unknown. In this study, we first aimed to evaluate the effect
      of bright light exposure before bedtime on frontal lobe activity the following
      morning using near-infrared spectroscopy (NIRS) during a Go/NoGo task. Second, we
      aimed to evaluate the effects of bright light exposure before bedtime on
      polysomnographic measures and on a frontal lobe function test the following
      morning. METHODS: Twenty healthy, young males (mean age, 25.5 years) were
      recruited between September 2013 and August 2014. They were first exposed to
      control light (150 lux) before bedtime (from 20:00 h to 24:00 h) for 2 days and
      then to bright light (1,000 lux) before bedtime for an additional 5 days. We
      performed polysomnography (PSG) on the final night of each light exposure period
      (on nights 2 and night 7) and performed NIRS, which measures the concentrations
      of oxygenated and deoxygenated hemoglobin (OxyHb and DeoxyHb, respectively),
      coupled with a Go/NoGo task the following morning (between 09:30 h and 11:30 h).
      The participants also completed frontal lobe function tests the following
      morning. RESULTS: NIRS showed decreased hemodynamic activity (lower OxyHb and a
      tendency toward higher DeoxyHb concentration) in the right frontal lobe during
      the NoGo block after 1000-lux light exposure compared with that during the NoGo
      block after 150-lux light exposure. The commission error rate (ER) during the
      Go/NoGo task was higher after 1000-lux light exposure than that during the
      Go/NoGo task after 150-lux light exposure (1.24 +/- 1.09 vs. 0.6 +/- 0.69, P =
      0.002), suggesting a reduced inhibitory response. CONCLUSION: This study shows
      that exposure to bright light before bedtime for 5 days impairs right frontal
      lobe activation and response inhibition the following morning.

PMID- 29580073
TI  - The Effects of the Perception of Being Recognized by Patients With Alzheimer
      Disease on a Caregiver's Burden and Psychophysical Health.
AB  - Caring for a patient with Alzheimer disease (AD) represents a real challenge that
      can have considerable long-term psychological and physical consequences. The aim
      of this study was to evaluate the impact of the perception of being recognized on
      both the psychophysical health and the level of burden reported in caregivers of
      patients with AD. The secondary aim was to evaluate the association between the
      use of a home care assistance service and the burden and psychophysical health in
      caregivers. The Caregiver Burden Inventory (CBI), the 36-item Short-Form Health
      Survey (SF-36), and a visual analog scale (VAS) to evaluate the level of
      perception of being recognized were administered to 31 caregivers of patients
      with AD. Data were also collected from patients with AD using the Mini-Mental
      State Examination (MMSE). The level of perception of being recognized was
      significantly and negatively correlated with total burden ( r = -0.36; P = .045)
      and objective burden ( r = -0.53; P = .002). It was also significantly and
      positively correlated with the MMSE score ( r = 41; P = .02). Regression models
      showed that only the perception of being recognized, and not MMSE, significantly
      predicted lower caregiver objective burden scores. Furthermore, the use of a home
      care assistance service significantly predicted higher caregiver physical
      functioning. The perception of being recognized by an AD relative significantly
      predicted the caregiver's objective burden associated with a shortage of time.
      The use of a home care assistance service also resulted in a promotion in the
      caregiver's social functioning. Further studies are needed to confirm these
      results.

PMID- 29580074
TI  - Early Palliative Care for Patients With Brain Metastases Decreases Inpatient
      Admissions and Need for Imaging Studies.
AB  - BACKGROUND: Early encounters with palliative care (PC) can influence health-care
      utilization, clinical outcome, and cost. AIM: To study the effect of timing of PC
      encounters on brain metastasis patients at an academic medical center.
      SETTING/PARTICIPANTS: All patients diagnosed with brain metastases from January
      2013 to August 2015 at a single institution with inpatient and/or outpatient PC
      records available for review (N = 145). DESIGN: Early PC was defined as having a
      PC encounter within 8 weeks of diagnosis with brain metastases; late PC was
      defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts
      of early (n = 46) and late (n = 46) PC patients were compared to control for
      differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis.
      Details of the palliative encounter, patient outcomes, and health-care
      utilization were collected. RESULTS: Early PC versus late PC patients had no
      differences in baseline KPS, age, or gender. Early PC patients had significantly
      fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency
      department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed
      tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8
      vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were
      no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following
      inpatient admissions, early PC patients were more likely to be discharged home
      (59% vs 35%; P = .04). CONCLUSIONS: Timely PC consultations are advisable in this
      patient population and can reduce health-care utilization.

PMID- 29580075
TI  - The Determinants of Palliative Care Use in Patients With Colorectal Cancer: A
      National Study.
AB  - BACKGROUND: Palliative care is associated with improved survival and quality of
      life, but its use among patients with colorectal cancer varies nationwide and the
      determinants of those variations are not clear. OBJECTIVE: To determine the
      factors associated with palliative care use among patients who died of colorectal
      cancer. METHODS: Deceased patients treated for colorectal cancer (2004-2013) were
      identified within the National Cancer Database. Multivariable logistic regression
      was used to evaluate patient and institutional characteristics associated with
      palliative care use. Patients were classified based on their length of survival
      (<6 months, 6-24 months, and 24+ months) to provide timing context. RESULTS: A
      total of 287 923 patients were analyzed. Overall, 4.3% of the patients received
      palliative care. Patients who received palliative care were more likely to be
      younger, recently diagnosed, treated at academic hospitals, and have stage IV
      disease. Patients living in Mountain and Pacific regions had higher odds of
      palliative care receipt than those in the East Coast. Patients without insurance
      had higher odds of palliative care if they survived <24 months. Insurance
      coverage through Medicaid was associated with increased palliative care use among
      patients who survived 6 to 24 months. Patients who survived <6 months and lived
      >9 miles from the institution received more palliative care. CONCLUSION:
      Palliative care use among patients with colorectal cancer is associated with a
      younger age, a more recent year of diagnosis, insurance status, academic
      hospitals, and living in Mountain and Pacific regions.

PMID- 29580076
TI  - Analyses of separate and concatenated cox1 and 18S rRNA gene sequences indicate
      that the bat piroplasm Babesia vesperuginis is phylogenetically close to
      Cytauxzoon felis and the 'prototheilerid' Babesia conradae.
AB  - Babesia vesperuginis is the only piroplasm known to infect bats. Unlike most
      members of the genus Babesia, it is probably transmitted by a soft tick species
      (i.e. Argas vespertilionis). Recently, two studies have been conducted to clarify
      the phylogenetic status of this species, and both agreed on placing it into a
      basal position among Babesia sensu stricto (s.s.). However, several important
      groups of piroplasms were not included in the already reported phylogenetic trees
      of B. vesperuginis isolates. Therefore, the aim of the present study was to
      amplify an approx. 950-bp fragment of the cytochrome c oxidase subunit 1 (cox1)
      gene of B. vesperuginis from A. vespertilionis specimens, and to compare its
      sequences with those from other piroplasmid groups in a broader phylogenetic
      context. Sequence comparisons focusing on either 18S rRNA or cox1 genes, as well
      as phylogenetic analyses involving separate and concatenated 18S rRNA and cox1
      sequences indicate that B. vesperuginis is more closely related to the
      phylogenetic group of Theileriidae than to Babesia s.s. In particular, B.
      vesperuginis clustered closest to Cytauxzoon felis and the 'prototheilerid' B.
      conradae. The results of this study highlight that B. vesperuginis is a unique
      and taxonomically important species, which should be included in future studies
      aimed at resolving the comprehensive phylogeny of Piroplasmida.

PMID- 29580078
TI  - Characterisation of a multiresistant Pasteurella multocida strain isolated from
      cattle.
AB  - The emergence of simultaneous resistance to multiple classes of antibiotics
      presents an increasing threat. Plasmid-borne multiresistance and integrative
      conjugative elements have been reported in Pasteurella multocida. We report an
      alternative strategy for the development of multiresistance observed in a P.
      multocida strain (Pm238) isolated from calf pneumonia. We identified genes
      integrated into the chromosomal DNA without known integrative and conjugative
      elements. These genes conferred resistance to streptomycin (strA), tetracycline
      (tetB), chloramphenicol (catAIII), and sulphonamides (sulII). We also detected
      mutation in the quinolone-resistance-determining regions of parC. No plasmids
      could be isolated from strain Pm238. These results suggest that P. multocida can
      accumulate multiple resistance determinants on the chromosome as single genes.

PMID- 29580077
TI  - Caffeine strongly improves motility parameters of turkey spermatozoa with no
      effect on cell viability.
AB  - The purpose of this study was to evaluate the impact of caffeine on turkey
      spermatozoa during in vitro incubation. Experimental samples were prepared by
      diluting the raw semen with nine different concentrations of caffeine - from
      0.078125 mg/mL to 10 mg/mL. The individual motility parameters were evaluated by
      the Computer Assisted Semen Analyser (CASA) system, and the viability of
      spermatozoa was evaluated using eosin-nigrosin staining. Selected parameters were
      recorded at six time periods: 0, 1, 2, 3, 4 and 5 h at 5  degrees C and 41 
      degrees C. A significantly higher motility and progressive motility of
      spermatozoa (P < 0.01 and P < 0.001, respectively) was detected in the samples
      containing caffeine ranging from 0.15625 to 7.5 mg/mL as compared to the control
      sample at 5  degrees C. At an incubation temperature of 41  degrees C the
      positive effect of caffeine on motility parameters was observed only at the
      beginning of incubation (at times 0 and 1). The tested caffeine concentrations
      showed no significant effect on the viability of turkey spermatozoa at any time
      period of incubation. A higher percentage of dead spermatozoa was observed for
      incubation at 41  degrees C (from 5.96% to 11.1%) in comparison to 5  degrees C
      (from 1.62% to 5.79%). The results suggest that caffeine can be used as a
      suitable component of turkey semen extenders and has the potential to improve
      fertility.

PMID- 29580079
TI  - Metagenomic analysis of bat guano samples revealed the presence of viruses
      potentially carried by insects, among others by Apis mellifera in Hungary.
AB  - The predominance of dietary viruses in bat guano samples had been described
      recently, suggesting a new opportunity to survey the prevalence and to detect new
      viruses of arthropods or even plant-infecting viruses circulating locally in the
      ecosystem. Here we describe the diversity of viruses belonging to the order
      Picornavirales in Hungarian insectivorous bat guano samples. The metagenomic
      analysis conducted on our samples has revealed the significant predominance of
      aphid lethal paralysis virus (ALPV) and Big Sioux River virus (BSRV) in Hungary
      for the first time. Phylogenetic analysis was used to clarify the relationship to
      previously identified ALPV strains infecting honey bees, showing that our strain
      possesses a close genetic relationship with the strains that have already been
      described as pathogenic to honey bees. Furthermore, studies have previously
      confirmed the ability of these viruses to replicate in adult honey bees; however,
      no signs related to these viruses have been revealed yet. With the identification
      of two recently described possibly honey bee infecting viruses for the first time
      in Hungary, our results might have importance for the health conditions of
      Hungarian honey bee colonies in the future.

PMID- 29580080
TI  - Coronavirus infection retards the development of the cortico-medullary capillary
      network in the bursa of Fabricius of chicken.
AB  - Coronavirus infection delays the development of the cortico-medullary (CM)
      capillary network which results in retarded development of bursal follicles. The
      smaller size of the medulla in the coronavirus-infected birds may lead to a lower
      number of B lymphocytes and bursal secretory dendritic cells, which negatively
      affects the reactivity and efficacy of the immune system. Contrary to the wild
      type infectious bronchitis virus (IBV) strain, infection induced by H120 vaccine
      virus exerts only a moderate influence on caveolin-1 expression of the CM
      capillary web and on follicular development compared to the untreated controls.

PMID- 29580081
TI  - Pulmonary hypertensive response of broiler chickens to arginine and
      guanidinoacetic acid under high-altitude hypoxia.
AB  - This study assessed the preventive effects of arginine (ARG) and guanidinoacetic
      acid (GAA) on the incidence of pulmonary hypertension syndrome (PHS) in broiler
      chickens. Four isoenergetic and isonitrogenous diets were prepared, including:
      (i) the control, (ii) the control supplemented with 1 g/kg ARG, (iii) the control
      supplemented with 1 g/kg GAA, and (iv) the control supplemented with 1.5 g/kg
      GAA. These diets were fed to broilers (Ross 308) from day 1 to 42 post-hatch.
      Criteria evaluated in the experiment were growth performance, carcass
      characteristics, serum and blood variables, lead-II electrocardiogram, and ET-1
      and iNOS gene expression in heart and lungs. Mortality from PHS was recorded
      daily. The results showed that ARG and GAA supplements improved the feed
      conversion ratio (FCR) compared to the control (P < 0.05). Supplementation of ARG
      and GAA significantly (P < 0.05) increased serum nitric oxide (NO) concentration.
      ARG and GAA supplementation significantly reduced the haematocrit value and the
      heterophil to lymphocyte ratio in the blood. A significant (P < 0.05) decline in
      S-wave amplitude of the lead-II electrocardiogram, right to total ventricular
      weight ratio (RV:TV) and ascites mortality was observed by supplementing ARG or
      1.5 g/kg GAA. Addition of ARG and GAA supplements did not significantly change ET
      1 and iNOS gene expression in the heart and lung relative to the control. In
      conclusion, GAA supplementation at 1.5 g/kg had a potential to improve growth
      performance and could prevent PHS.

PMID- 29580082
TI  - Association of amniotic uric acid, glucose, lactate and creatinine concentrations
      and lactate/creatinine ratio with newborn survival in small-sized dogs -
      preliminary results.
AB  - In order to define the normal composition of canine amniotic fluid and to detect
      differences between surviving and non-surviving newborn puppies, the present
      study determined the uric acid, glucose, lactate and creatinine concentrations
      and the lactate to creatinine ratio in amniotic fluids collected during elective
      Caesarean section from small-sized purebred bitches. The possible relationship
      between newborn survival and the studied parameters, as well as the effects of
      maternal parity, fetal gender and Apgar score were assessed. The study enrolled
      27 small-sized purebred bitches submitted to elective Caesarean section at term.
      After opening the fetal membranes, amniotic fluid samples were collected
      aseptically from the amniotic sac of each fetus. The data obtained from 74
      amniotic fluid samples collected from 27 bitches showed that amniotic glucose
      concentration was lower (P < 0.05) in non-surviving than in surviving puppies.
      Within the normal, surviving puppies, amniotic glucose concentration was higher
      (P < 0.05) in male than in female newborns, and the lactate/creatinine ratio was
      significantly higher in multiparous than in primiparous bitches (P < 0.05). These
      preliminary results demonstrate the relevance of amniotic glucose, but not of
      uric acid, lactate, creatinine and the lactate to creatinine ratio for detecting
      puppies at risk of death immediately after birth.

PMID- 29580083
TI  - Rapid in-house detection method of Campylobacter spp. from food by redox
      potential monitoring combined with real-time PCR.
AB  - The rapid detection of Campylobacter spp. is of utmost importance for the
      reduction of infections in humans by contaminated food products. The standard
      culturing method (ISO 10272-1:2006) involves a high time and labour demand. In
      this paper, we present a method that reduces the detection time of Campylobacter
      spp. to or below one third as compared to the ISO method, at a reduced cost per
      test. We used redox potential change of enrichment cultures (Bolton broth with
      Bolton selective supplement) for reliably selecting Campylobacter-contaminated
      raw milk and broiler meat samples. Identification of Campylobacter spp. in the
      contaminated samples was done by real-time PCR method. Culturing time to
      conclusive redox monitoring varied between 6 and 24 h for positive samples,
      depending on the contamination rate, in contrast to 136 h with the standard
      culturing process. However, now the Campylobacter-negative majority of food
      samples will not need to be tested by real-time PCR because redox potential
      monitoring can identify them in the selective enrichment phase. This method could
      be potentially used as a faster alternative to the current standard ISO 10272
      1:2006, for nonregulatory monitoring purposes.

PMID- 29580084
TI  - Effect of methionine deficiency on oxidative stress and apoptosis in the small
      intestine of broilers.
AB  - The aim of this study was to investigate the effects of methionine (Met)
      deficiency on antioxidant functions (in the duodenal, jejunal and ileal mucosa)
      and apoptosis in the duodenum, jejunum and ileum of broiler chickens. A total of
      120 one-day-old Cobb broilers were divided into two groups and fed a Metdeficient
      diet and a control diet, respectively, for six weeks. The activities of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px),
      the ability to inhibit hydroxyl radicals, and glutathione (GSH) content were
      significantly decreased in the Met-deficient group compared to the control. In
      contrast, malondialdehyde (MDA) content was significantly higher in the Met
      deficient group. As measured by terminal deoxynucleotidyl transferase 2'
      deoxyuridine 5'- triphosphate dUTP nick end-labelling (TUNEL) and flow cytometry
      (FCM), the percentages of apoptotic cells were significantly increased. In
      conclusion, dietary Met deficiency can cause oxidative stress and then induce
      increased apoptosis in the intestine. Oxidative stress contributes to intestinal
      apoptosis. This results in the impairment of local intestinal mucosal immunity
      due to oxidative stress and apoptosis in the small intestine. The results of this
      study provide new experimental evidence for understanding the negative effects of
      Met deficiency on mucosal immunity or the functions of other immune tissues.

PMID- 29580085
TI  - Monitoring minimal residual disease in canine lymphomas treated with modified L
      COP or L-CHOP protocols.
AB  - Heteroduplex polymerase chain reaction for antigen receptor rearrangements
      (hPARR) was developed to monitor minimal residual disease (MRD) in canine B- and
      T-cell lymphomas treated with the modified L-COP or L-CHOP protocol. Thirty-five
      dogs were recruited in this study and their neoplastic lineages were determined
      by immunophenotyping with Pax5 and CD3. Peripheral blood leukocytes were
      collected prior to and during chemotherapy in weeks 4, 9 and 13 to detect MRD by
      hPARR. Twenty-eight dogs (80%) had B-cell lymphoma while seven dogs (20%) had T
      cell lymphoma. A monoclonal band was detected in 11 cases that showed complete or
      partial remission before tumour relapse and no response to the current treatment
      without statistical difference in clinical outcomes; however, the treatment
      response had an association with the MRD result (P < 0.05). Modified L-CHOP
      prolonged median progression-free survival as compared to modified L-COP (215
      days vs. 93 days; P < 0.05). Substage b had shorter progression-free survival
      than substage a (90 days vs. 215 days; P < 0.05). Clinical stage III affected
      median overall survival time when compared to clinical stages IV and V (432, 173
      and 118 days, respectively; P < 0.05). hPARR could be used for screening
      refractory lymphoma together with lymph node measurement in routine clinical
      cases.

PMID- 29580086
TI  - Short-term effects of T-2 toxin or deoxynivalenol on glutathione status and
      expression of its regulatory genes in chicken.
AB  - Short-term (48-hour) effects of 3.74/1.26 mg kg-1 T-2/HT-2 toxin or 16.12 mg kg-1
      DON in feed were investigated in the liver of three-week-old cockerels (body
      weight: 749.60 +/- 90.98 g). Markers of lipid peroxidation showed no significant
      changes. At hour 24, glutathione content in the T-2/HT-2 toxin group was
      significantly higher than in the control. Glutathione peroxidase activity was
      significantly higher than the control at hour 24 in the T-2/H-2 toxin group and
      at hour 48 in the DON group. In the DON group, expression of the glutathione
      peroxidase 4 gene (GPX4) was significantly lower than in the control at hours 12
      and 14, and higher at hour 48. Expression of the glutathione reductase gene (GSR)
      was significantly lower than in the control at hour 12 in the T-2/HT-2 toxin
      group, and at hours 12, 24 and 48 in the DON group. However, at hour 36 higher
      GSR expression was measured in the DON group. Due to the effect of both
      trichothecenes, expression of the glutathione synthetase gene (GSS) was
      significantly lower than in the control at hours 24 and 48. In conclusion, T-2/HT
      2 toxin and DON had a moderate short-term effect on free radical formation. T
      2/HT-2 toxin induced more pronounced activation of the glutathione redox system
      than did DON.

PMID- 29580088
TI  - Effect of fulvic and humic acids on copper and zinc homeostasis in rats.
AB  - The objective of this study was to investigate the effects of fulvic acid (FA)
      and humic acid (HA), the two main compounds of humic substances (HSs), on copper
      (Cu) and zinc (Zn) homeostasis. Seventy-two male Wistar rats were randomly
      divided into nine experimental groups. The control diet (AIN-93G formula) and the
      diets supplemented with 0.1%, 0.2%, 0.4% and 0.8% FA or HA were fed for 26 days.
      Cu and Zn concentrations of the large intestinal content (LIC), liver, kidney,
      femur and hair were determined. FA and HA did not influence significantly the Cu
      or Zn contents of the experimental diets, the rats' feed intake, weight gain and
      the feed to gain ratio. Both FA and HA decreased the Cu concentrations of the LIC
      significantly and in a dose-related manner; however the absorption-stimulating
      effect of HA was more pronounced. FA increased the Cu content of the liver, but
      neither FA nor HA had a dose-dependent effect on it. FA or HA supplementations
      had no significant effect on the Cu concentration of the kidney. At the
      concentrations used, dietary FA or HA supplementations are not promising growth
      promoters. FA influences the Cu homeostasis unlike HA, because FA not only
      stimulates Cu absorption, but the extra quantity of absorbed Cu is retained in
      the organism. The stimulatory effect of HA on Zn absorption may not be manifested
      in Cu and Zn homeostasis, because of the tight connection of these microelements
      to FA and HA, which prevents the transmission of Zn from the ZnHA complex to the
      organs. As regards the effect of FA and HA on Cu and Zn homeostasis, both FA and
      HA stimulated the absorption of these microelements, but only FA increased the
      retention of Cu (in the liver) and Zn (in the kidney).

PMID- 29580089
TI  - Detection and molecular characterisation of Ehrlichia canis in naturally infected
      dogs in South West Nigeria.
AB  - Canine ehrlichiosis is an important tick-borne rickettsial disease mainly caused
      by Ehrlichia canis. This study aimed to detect and characterise E. canis in dogs
      in Abeokuta, Nigeria by microscopy and nested PCR. Blood samples were collected
      from 205 dogs, thin smears were made, field-stained, and DNA was extracted from
      the blood samples. A partial region of the 16S rRNA gene was amplified by
      polymerase chain reaction (PCR) and sequenced unidirectionally. Ehrlichial
      morulae were detected in three dogs (1.5%). The PCR test revealed that 47 dogs
      (22.9%) were positive for E. canis. The lengths of the sequences obtained range
      from 374 bp to 376 bp with an average G-C content of 37% and 98-99% homology with
      the reference sequences in GenBank. The aligned autochthonous sequences were less
      polymorphic. The phylogenetic analysis separated sequences reported previously in
      Nigeria from the autochthonous sequences. The present work shows that the strain
      of E. canis detected in the study area is genetically different from those
      reported in the northern part of Nigeria and more closely related to sequences
      from Brazil and India.

PMID- 29580090
TI  - Helminths of European smelt Osmerus eperlanus (Linnaeus, 1758) in Lake Hancza and
      the Vistula Lagoon, with special regard to their zoonotic threats.
AB  - Reports published in recent years on the increased risk in the Baltic Sea of fish
      infection with larvae of nematodes potentially pathogenic to humans have prompted
      a study of European smelt Osmerus eperlanus with respect to the presence of these
      parasites in the Vistula Lagoon. Additionally, samples of this fish from Lake
      Hancza were comparatively considered. The body cavity, the surface of internal
      organs, the alimentary tract and the swimbladder of fish from two environmentally
      different water bodies were taken into account in the analysis. Only the tapeworm
      Proteocephalus longicollis was found in the alimentary tract of the fish from
      Lake Hancza. Depending on the period of study, the prevalence ranged from 60% to
      100%, and the mean intensity from 11.5 to 42.0. The helminth fauna of smelt from
      the Vistula Lagoon was more diverse: Cystidicola farionis occurred with a
      prevalence from 25.9 to 75.0% and a mean intensity of infection from 2.7 to
      66.0%, Proteocephalus longicollis and cystacanths of Corynosoma with a prevalence
      ranging in different years from 12.0 to 44.0% and from 14.8 to 50.0%,
      respectively. Zoonotic parasites, such as nematode larvae of the Anisakidae
      family (Contracaecum sp., Anisakis simplex), occurred in the intestine with a
      prevalence of 31%, 72% and 22% in consecutive years of the study.

PMID- 29580091
TI  - Maternal-Neonatal Pheromone/Interomone Added to Cat Litter Improves Litter Box
      Use and Reduces Aggression in Pair-Housed Cats.
AB  - Introducing a new cat into a household with one or more resident cats can be a
      significant source of stress for the cats involved. These studies sought to
      determine if rabbit maternal-neonatal pheromone (2-methyl-2-butenal [2M2B]) in
      litter impacted cat social behaviors and litter box use. Study 1 determined that
      cats preferred to eliminate in litter containing 2M2B; other semiochemicals
      tested did not change litter box use. Cats prone to aggression were identified in
      an intermediate pilot study, and eight pairs of these cats were selected for
      Study 2. In Study 2, cat pairs were provided litter containing either vehicle or
      2M2B for 24 hours. Cats experiencing control litter displayed more aggression
      during the first 6 hours (p < .01) and spent more time using the litter box 12
      hours and 18 hours after pairing compared with cats experiencing litter with 2M2B
      (p = .02). These results suggest 2M2B-infused cat litter may act as an interomone
      in cats housed domestically to prevent initial occurrences of aggression and may
      improve cat welfare in multicat households.

PMID- 29580092
TI  - Ventral tegmental area inactivation alters hormonal, metabolic, and locomotor
      responses to inescapable stress.
AB  - CONTEXT: The involvement of unilateral and bilateral inhibition of the ventral
      tegmental area (VTA) in response to stress is not well understood. OBJECTIVE: In
      the present study, the effect of unilateral and bilateral inhibition of the VTA
      on hormonal, metabolic, and locomotor responses to stress was assessed. MATERIAL
      AND METHODS: Male rats seven days after cannulation into the VTA received electro
      foot-shock stress for seven consecutive days. Twenty minutes before induction of
      stress, 2% lidocaine hydrochloride or sterile saline (control) was injected
      either uni- or bi-laterally into the VTA. RESULTS: Results showed that stress
      significantly increased serum corticosterone level, adrenal gland weight and
      anorexia, reduced weight gain, food-intake, and locomotor activity. However,
      bilateral inactivation of VTA prevented stress-induced these parameters changes.
      CONCLUSION: The present study demonstrated that the bilateral VTA blockade
      effectively relieves the symptoms of stress, while the unilateral VTA blockade
      does not significantly improve the changes caused by stress.

PMID- 29580093
TI  - What is the relationship between self-reported aberrant driving behaviors,
      mindfulness, and self-reported crashes and infringements?
AB  - OBJECTIVES: This study investigated the relationship between self-reported
      aberrant driving behaviors, mindfulness, and self-reported crashes and
      infringements. METHODS: Three hundred and eighteen participants (M = 46.0 years,
      SD = 13.7 years; female: 81.8%) completed an online survey that assessed aberrant
      driving behaviors, mindfulness (including regular mindfulness meditation [MM]),
      and self-reported crashes and infringements during the past 2 years. Structural
      equation modeling (SEM) was used to examine the relationship between self
      reported aberrant driving behaviors and mindfulness simultaneously, as well as
      with participants' age and estimated kilometers driven over the past year.
      RESULTS: The results of the SEM showed that mindfulness was negatively related to
      each self-reported aberrant driving behavior, with the strongest relationships
      being between mindfulness and driving-related lapses (-0.58) and errors (-0.46).
      Participants who practice MM had significantly fewer crashes in the past 2 years
      and reported significantly fewer driving-related violations and lapses compared
      to participants who did not practice MM (crashes: 9.3% vs. 18.8%, P < .05;
      violations: M = 6.66 [SD = 3.44] vs. M = 7.68 [SD = 4.53], P < .05; errors: M =
      5.17 [SD = 3.44] vs. M = 6.19 [SD = 4.12], P < .05). CONCLUSIONS: More research
      is needed to understand whether MM results in more mindful and attentive drivers
      or whether individuals who practice MM may have other traits or behaviors that
      are linked to improved safety.

PMID- 29580094
TI  - Outcomes of Noninvasively Treated Idiopathic Toe Walkers.
AB  - : Idiopathic toe walking (ITW) causes a common problem in pediatric orthopaedics.
      In the literature, numerous treatment options have been reported, but consensus
      about the management of ITW is still missing. The aim of the current study was to
      evaluate conservative treatment with pyramidal insoles. A total of 193 patients
      underwent conservative treatment between January 2010 and June 2013. Mean age at
      the beginning of the treatment was 7.75 +/- 0.23 years (range 2.0-17.0 years).
      For all patients, demographic data, comorbid diseases, passive range of motion
      (ROM), persistent toe walking, and performed operations were retrospectively
      evaluated. Following operative treatment was defined failure. Eight (4.15%)
      patients underwent Achilles tendon lengthening operation after mean therapy time
      of 2.72 years (range 0.1-7.0 years), 174 cases were treated successfully
      (90.16%). In 50 cases, toe walking suspended completely after mean therapy time
      of 2.83 years. In cases of failure, patients were older at diagnosis and at the
      beginning of the treatment. Mean passive ROM increased over the time. In cases of
      failure, ROM decreased from the first to the second examination. Conservative
      treatment of ITW using pyramidal insoles can be effective. Ankle dorsiflexion
      significantly improved in the patients who were successfully treated. Therapy
      should start early. A decrease of ROM under therapy should lead to critical
      revisal of individual therapy. LEVELS OF EVIDENCE: Therapeutic, level IV: Case
      series.

PMID- 29580095
TI  - Minimal Invasive Fixation Can Decrease Infection Rates in Diabetic and Obese
      Patients With Severe Ankle Fracture and Syndesmotic Injury.
AB  - BACKGROUND: Ankle fractures involving syndesmosis disruption cause severely
      unstable joint conditions. Traditional invasive operations put certain patient
      groups at an increased risk of infection. There is limited literature discussing
      the outcomes of minimally invasive fixation of severe ankle fractures including
      syndesmotic injury, as clinicians may be tempted to treat these difficult cases
      with open reduction internal fixation (ORIF). METHODS: A retrospective case
      control study was conducted on patients treated at a level one trauma center.
      Patients were divided into 2 groups based on presence of diabetes and/or obesity
      (body mass index >=30.0 kg/m2). Those with either comorbidity were defined as
      high infection risk patients and placed in a comorbidity group. Patients were
      further divided into subgroups based on the operation's invasiveness; either
      traditional ORIF or percutaneous cannulated screw fixation. RESULTS: Comorbid
      patients (N = 67) were more likely to sustain Weber C fractures compared to
      noncomorbid patients (N = 43) (59.70% to 37.21%, P = .019). Additionally,
      patients receiving minimally invasive fixation procedures experienced fewer
      infections than those receiving ORIF (0 vs 11 incidences, P = .01), without
      effect on union rates, fracture reduction, pain, need for revision surgery, or
      time to full weightbearing. CONCLUSIONS: Diabetic and obese patients are at an
      increased risk of experiencing severe ankle fractures. The use of minimally
      invasive fixation methods can reduce the risk of postoperative infection without
      sacrificing other surgical outcomes, even with fractures involving syndesmotic
      injury. LEVELS OF EVIDENCE: Therapeutic, Level III: Retrospective comparative
      study.

PMID- 29580096
TI  - Comparison of intensive versus conventional insulin therapy in traumatic brain
      injury: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To compare intensive insulin therapy (IIT) and conventional insulin
      therapy (CIT) on clinical outcomes of patients with traumatic brain injury (TBI).
      METHODS: MEDLINE, EMBASE, Google Scholar, ISI Web of Science, and Cochrane
      Library were systematically searched for randomized controlled trials (RCTs)
      comparing IIT to CIT in patients with TBI. Study-level characteristics, intensive
      care unit (ICU) events, and long-term functional outcomes were extracted from the
      articles. Meta-analysis was performed with random-effect models. RESULTS: Seven
      RCTs comprising 1070 patients were included. Although IIT was associated with
      better neurologic outcome (GOS > 3) (RR=0.87, 95% CI=0.78-0.97; P=0.01; I2=0%),
      sensitivity analysis revealed that one study influenced this overall estimate
      (RR=0.90, 95% CI=0.80-1.01, P=0.07; I2=0%). IIT was strongly associated with
      higher risk of hypoglycaemia (RR=5.79, 95% CI=3.27-10.26, P<0.01; I2=38%). IIT
      and CIT did not differ in terms of early or late mortality (RR=0.96, 95% CI=0.79
      1.17, P=0.7; I2=0%), infection rate (RR=0.82, 95% CI=0.59-1.14, P=0.23; I2=68%),
      or ICU length of stay (SMD= -0.14, 95% CI=-0.35 to 0.07, P=0.18; I2=45%0.)
      Conclusions: IIT did not improve long-term neurologic outcome, mortality, or
      infection rate and was associated with increased risk of hypoglycaemia.
      Additional well-designed RCTs with defined TBI subgroups should be performed to
      generate more powerful conclusions.

PMID- 29580097
TI  - The Influence of Materialism on Purebred Dogs' Welfare Among Two Different
      Generations in Colombia (South America).
AB  - Some consumers in Colombia show a clear preference for purebred dogs. At the same
      time, there are many abandoned dogs on the streets and in shelters in this
      country. Previous research has revealed that appearances of the breeds influence
      the caregivers' (owners') choice. A choice based on appearances has been
      connected with materialism in the psychology and consumer behavior literature.
      Buying purebred dogs based on materialistic standards could affect the welfare of
      these nonhuman animals. With the use of quantitative research and the methodology
      of structural equation modeling, this research demonstrated that more
      materialistic consumers in Colombia have purebred dogs who, in the owners'
      opinions, show more behavioral problems. Furthermore, the results showed that
      materialism influenced the owners' intentions to abandon their companion animals
      when they perceived these problems. Finally, this research examined the
      moderating effect of generational segmentation regarding these relationships. It
      was observed that the intention to abandon the dogs was greater among members of
      Generation X than among members of Generation Y.

PMID- 29580098
TI  - Three new triterpenoid saponins from the stems of Ilex asprella.
AB  - Three new triterpenoid saponins, namely asprellinoids A-C (1-3), featuring a
      sulfate substitution in sugar moiety, were isolated from the stems of Ilex
      asprella (Hook. et Arn.) Champ. ex Benth. Their structures were elucidated by the
      spectroscopic data analyses including HR-ESI-MS, IR, and NMR spectra, and
      chemical method.

PMID- 29580099
TI  - Global medicinal chemistry and GPCR conference: interview with Stevan Djuric.
AB  - Stevan Djuric speaks to Benjamin Walden, Commissioning Editor. Stevan Djuric is
      head of the global Medicinal Chemistry Leadership Team at AbbVie and is also Vice
      President of the Discovery Chemistry and Technology organization within their
      Discovery organization and chemistry outsourcing activities. He spoke at the
      Global-Medicinal-Chemistry and GPCR summit on the imperative to develop chemistry
      related technology that can reduce cycle time, cost of goods and improve
      probability of success. To this end, he discussed his efforts in the chemistry
      technology area with a focus on integrated synthesis-purification bioassay, and
      flow photochemistry and high temperature chemistry platforms.

PMID- 29580100
TI  - Assessment of AAV Vector Tropisms for Mouse and Human Pluripotent Stem Cell
      Derived RPE and Photoreceptor Cells.
AB  - Adeno-associated viral vectors are showing great promise as gene therapy vectors
      for a wide range of retinal disorders. To date, evaluation of therapeutic
      approaches has depended almost exclusively on the use of animal models. With
      recent advances in human stem cell technology, stem cell-derived retina now
      offers the possibility to assess efficacy in human organoids in vitro. Here we
      test six adeno-associated virus (AAV) serotypes [AAV2/2, AAV2/9, AAV2/8,
      AAV2/8T(Y733F), AAV2/5, and ShH10] to determine their efficiency in transducing
      mouse and human pluripotent stem cell-derived retinal pigment epithelium (RPE)
      and photoreceptor cells in vitro. All the serotypes tested were capable of
      transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the
      most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and
      ShH10 achieved similarly robust transduction of human embryonic stem cell-derived
      cone photoreceptors. Furthermore, we show that human embryonic stem cell-derived
      photoreceptors can be used to establish promoter specificity in human cells in
      vitro. The results of this study will aid capsid selection and vector design for
      preclinical evaluation of gene therapy approaches, such as gene editing, that
      require the use of human cells and tissues.

PMID- 29580101
TI  - Application of energy derivative method to determine the structural components'
      contribution to deceleration in crashes.
AB  - OBJECTIVE: For occupant protection, it is important to understand how a car's
      deceleration time history in crashes can be designed using efficient of energy
      absorption by a car body's structure. In a previous paper, the authors proposed
      an energy derivative method to determine each structural component's contribution
      to the longitudinal deceleration of a car passenger compartment in crashes. In
      this study, this method was extended to 2 dimensions in order to analyze various
      crash test conditions. The contribution of each structure estimated from the
      energy derivative method was compared to that from a conventional finite element
      (FE) analysis method using cross-sectional forces. METHOD: A 2-dimensional energy
      derivative method was established. A simple FE model with a structural column
      connected to a rigid body was used to confirm the validity of this method and to
      compare with the result of cross-sectional forces determined using conventional
      analysis. Applying this method to a full-width frontal impact simulation of a car
      FE model, the contribution and the cross-sectional forces of the front rails were
      compared. In addition, this method was applied to a pedestrian headform FE
      simulation in order to determine the influence of the structural and inertia
      forces of the hood structures on the deceleration of the headform undergoing
      planar motion. RESULT: In an oblique impact of the simple column and rigid body
      model, the sum of the contributions of each part agrees with the rigid body
      deceleration, which indicates the validity of the 2-dimensional energy derivative
      method. Using the energy derivative method, it was observed that each part of the
      column contributes to the deceleration of the rigid body by collapsing in the
      sequence from front to rear, whereas the cross-sectional force at the rear of the
      column cannot detect the continuous collapse. In the full-width impact of a car,
      the contributions of the front rails estimated in the energy derivative method
      was smaller than that using the cross-sectional forces at the rear end of the
      front rails due to the deformation of the passenger compartment. For a pedestrian
      headform impact, the inertial and structural forces of the hood contributed to
      peaks of the headform deceleration in the initial and latter phases,
      respectively. CONCLUSIONS: Using the 2-dimensional energy derivative method, it
      is possible to analyze an oblique impact or a pedestrian headform impact with
      large rotations. This method has advantages compared to the conventional approach
      using cross-sectional forces because the contribution of each component to system
      deceleration can be determined.

PMID- 29580102
TI  - Ocular surface changes in recurrent pterygium cases post-operatively treated with
      5-fluorouracil subconjunctival injections.
AB  - INTRODUCTION: To investigate the ocular surface changes occurring in eyes with
      recurrent pterygium post-operatively treated with 5-fluorouracil intralesional
      injections. METHODS: Retrospective observational study of recurrent pterygium
      cases treated with weekly intralesional injections of 0.1 mL (5 mg) of 5
      fluorouracil (10 injections). Impression cytology samples taken from the lesion,
      the healthy conjunctivae (inferior, superior, and contralateral to injury), and
      the cornea before and after treatment were analyzed. Clinical ocular
      characteristics (including Schirmer's test and break-up time) were evaluated
      during treatment. RESULTS: A total of 15 eyes were treated, with the mean follow
      up of 27 +/- 8.7 months (mean +/- standard deviation). Prior to treatment
      initiation, the ocular surface citology over the pterygium was found to be
      abnormal. No epithelial cells (27%) and a lower goblet cell density (73%)
      compared to the healthy conjunctivae (p < 0.01) were found. Squamous metaplasia
      was observed to some degree in the cornea (100%), pterygium (81%) and healthy
      conjunctivae (73%). Following treatment, pterygium composition had changed:
      epithelial cell number (100%) and goblet cell density (47%) had increased (p <
      0.05). Goblet cell density was also increased in healthy conjunctivae (67%; p <
      0.05). The degree of squamous metaplasia decreased in the cornea (67%), pterygium
      (45%), and healthy conjunctivae (60%; p < 0.05). No adverse effects were
      reported, recurrence progression was arrested, and conjunctival redness and dry
      eye severity level were decreased in all cases (p < 0.01). DISCUSSION: The
      cytology of ocular surface in recurrent pterygium is abnormal. After weekly
      intralesional 5-fluorouracil injections, it tends to normalize. The 5
      fluorouracil compound is a safe and effective treatment to prevent pterygium
      recurrence.

PMID- 29580103
TI  - Distribution of keratometry and its determinants in a general population of 6- to
      12-year-old children.
AB  - PURPOSE: To determine the distribution of keratometry and its determinants in
      Iranian school children. METHODS: The present cross-sectional study was conducted
      in 2015 in Shahroud in the north of Iran. The entire rural population of
      elementary school children was invited to the study. In urban areas, cluster
      sampling was conducted. Pentacam HR (Oculus Inc., Lynnwood, WA) was used to
      measure the flat meridian, the steep meridian, and the mean keratometry. Linear
      regression was used to determine the associated variables with mean keratometry.
      RESULTS: Of 5620 participated in the study, 5559 children were analyzed after
      applying the exclusion criteria. Mean keratometry was 43.56 +/- 1.96 diopters (D)
      (95% confidence interval = 43.48-43.64) in the total sample, 43.18 +/- 2.23 D
      (95% confidence interval = 43.09-43.26) in boys, and 44.01 +/- 1.46 D (95%
      confidence interval = 43.95-44.07) in girls (p < 0.001). The highest and lowest
      mean keratometry was 43.28 +/- 1.66 D (95% confidence interval = 43.00-43.55) and
      42.89 +/-2.70 D (95% confidence interval = 42.68-43.11) in 6-year-old and 10-year
      old children, respectively (p = 0.031). The results of multiple linear regression
      showed that mean keratometry in girls was 0.82 D higher than in boys (p < 0.001),
      and in groups older than 9 years, it was significantly decreased. Mean
      keratometry in myopic children was 0.62 D higher than emmetropic children (p <
      0.001). CONCLUSION: This study provided valuable findings from the status of
      keratometry in Iranian children. In line with other studies, corneal power was
      higher in girls than in boys, and the cornea becomes flatter with age in
      children.

PMID- 29580105
TI  - Herbal Remedies: A Boon for Diabetic Neuropathy.
AB  - Diabetic neuropathy is a chronic complication of diabetes mellitus affecting
      about 50% of patients. Its symptoms include decreased motility and severe pain in
      peripheral parts. The pathogenesis involved is an abnormality in blood vessels
      that supply the peripheral nerves, metabolic disorders such as myo-inositol
      depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in
      neurons results in activation of multiple biochemical pathways, which results in
      the generation of free radicals. Apart from available marketed formulations,
      extensive research is being carried out on herbal-based natural products to
      control hyperglycemia and its associated complications. This review is focused to
      provide a summary on diabetic neuropathy covering its etiology, types, and
      existing work on herbal-based therapies, which include pure compounds isolated
      from plant materials, plant extracts, and Ayurvedic preparations.

PMID- 29580104
TI  - Soluble glycoprotein 130 is inversely related to severity of coronary
      atherosclerosis.
AB  - PURPOSE: Recent studies indicate that the effects of interleukin 6 (IL-6)
      realized via soluble IL-6 receptor (sIL-6R) facilitate the development of various
      pathological processes. Soluble gp130 (sgp130) is a naturally occurring inhibitor
      of signal transduction via this pathway. In this study, we assessed the
      relationship between circulating levels of IL-6, sIL-6R and sgp130 and severity
      of coronary atherosclerosis in patients with stable coronary artery disease
      (CAD). METHODS: Plasma levels of IL-6, sIL-6R and sgp130 were measured in
      patients with atherosclerotic coronary lesions (n = 128, group 1) and with intact
      coronary arteries (n = 48, group 2). The severity of coronary atherosclerosis was
      evaluated by the number of affected arteries and by Gensini Score index. RESULTS:
      Circulating IL-6 levels in group 1 were significantly higher than those in group
      2. The levels of sIL-6R did not differ considerably in both the groups. The
      levels of sgp130 in group 1 were significantly lower than in group 2. A negative
      correlation has been revealed between sgp130 levels and the number of affected
      coronary arteries and Gensini Score index. CONCLUSIONS: Serum concentration of
      sgp130 in patients with stable CAD is inversely related to severity of coronary
      damage. Low sgp130 level may serve as an additional indicator of coronary
      atherosclerosis severity.

PMID- 29580106
TI  - Flagellin as a vaccine adjuvant.
AB  - INTRODUCTION: Bacterial flagellin, as a pathogen-associated molecular pattern
      (PAMP), can activate both innate and adaptive immunity. Its unique structural
      characteristics endow an effective and flexible adjuvant activity, which allow
      the design of different types of vaccine strategies to prevent various diseases.
      This review will discuss recent progress in the mechanism of action of flagellin
      and its prospects for use as a vaccine adjuvant. Areas covered: Herein we
      summarize various types of information related to flagellin adjuvants from
      PubMed, including structures, signaling pathways, natural immunity, and extensive
      applications in vaccines, and it discusses the immunogenicity, safety, and
      efficacy of flagellin-adjuvanted vaccines in clinical trials. Expert commentary:
      It is widely accepted that as an adjuvant, flagellin can induce an enhanced
      antigen-specific immune response. Flagellin adjuvants will allow more effective
      flagellin-based vaccines to enter clinical trials. Furthermore, vaccine
      formulations containing PAMPs are crucial to exert the maximum potential of
      vaccine antigens. Therefore, combinations of flagellin-adjuvanted vaccines with
      other adjuvants that act in a synergistic manner, particularly TLR ligands,
      represent a promising method for tailoring targeted vaccines to meet specific
      requirements.

PMID- 29580107
TI  - Erratum.
AB  - Narayan SW, Jamieson HA, Nishtala PS. Evaluation of the National Minimum Data Set
      for Neurological Conditions in Older Adults. Journal of Geriatric Psychiatry and
      Neurology. 2017; 30(6):331-336. doi: 10.1177/0891988717732154 In the above
      referenced article, the corresponding author's qualifications were incorrectly
      listed as BPharm, MPharm, PG DipClinPharm, PhD which is an overlap of another
      author's qualifications. The online and print versions have been updated to
      reflect the correct qualification of the corresponding author as BPharm,
      MPharmPrac.

PMID- 29580108
TI  - The feasibility of assessing speech and non-speech function of the speech
      apparatus in adults with cerebral palsy.
AB  - This short note reports on observations concerning the feasibility of a set of
      speech and non-speech assessment tasks in an investigation of dysarthria in 21
      adults (15 males/6 females; median 23 years) with cerebral palsy and concomitant
      cognitive impairment. The participants were assessed with nine tasks representing
      standard components of clinical dysarthria assessment (i.e. six speech and three
      non-speech tasks). The tasks were evaluated for their feasibility on the basis of
      common clinical criteria. Our results indicated that, overall, speech tasks were
      more feasible than non-speech tasks. Several participants showed signs of
      dysexecutive behaviour on some of the non-speech tasks, but not on the speech
      tasks. The current note provides tentative clues regarding the impact of
      cognitive deficits on the feasibility of assessment tasks in the diagnosis of
      dysarthria.

PMID- 29580109
TI  - Total pathological complete response versus breast pathological complete response
      in clinical trials of reference and biosimilar trastuzumab in the neoadjuvant
      treatment of breast cancer.
AB  - INTRODUCTION: Trastuzumab is a key drug in the neoadjuvant treatment of breast
      cancers that overexpress the human epidermal growth factor receptor 2 (HER2).
      Pathological complete response (pCR) is commonly used as an endpoint in
      neoadjuvant clinical trials of trastuzumab as evidence suggests it may be a
      surrogate for long-term survival. Several biosimilar candidates of originator or
      'reference' trastuzumab are in development and have used pCR as a primary
      endpoint to assess therapeutic equivalence between treatments. The exact
      definition of pCR has varied across studies. Areas covered: Here we look at the
      clinical relevance of pCR and compare rates of total pCR (defined as ypT0/is
      ypN0) and breast pCR (defined as ypT0/is) in clinical trials of reference and
      biosimilar trastuzumab. Expert commentary: In order to evaluate the efficacy of
      neoadjuvant systemic therapies in a uniform way, standardization of trial
      endpoints is necessary. Future studies in HER2-positive breast cancer should
      include full assessment of the breast and lymph node basin before and after
      neoadjuvant systemic therapy, and the use of total pCR as the primary outcome.

PMID- 29580110
TI  - Current and future molecular approaches in the diagnosis of cystic fibrosis.
AB  - INTRODUCTION: Cystic Fibrosis is among the first diseases to have general
      population genetic screening tests and one of the most common indications of
      prenatal and preimplantation genetic diagnosis for single gene disorders. During
      the past twenty years, thanks to the evolution of diagnostic techniques, our
      knowledge of CFTR genetics and pathophysiological mechanisms involved in cystic
      fibrosis has significantly improved. Areas covered: Sanger sequencing and
      quantitative methods greatly contributed to the identification of more than 2,000
      sequence variations reported worldwide in the CFTR gene. We are now entering a
      new technological age with the generalization of high throughput approaches such
      as Next Generation Sequencing and Droplet Digital PCR technologies in diagnostics
      laboratories. These powerful technologies open up new perspectives for scanning
      the entire CFTR locus, exploring modifier factors that possibly influence the
      clinical evolution of patients, and for preimplantation and prenatal diagnosis.
      Expert commentary: Such breakthroughs would, however, require powerful
      bioinformatics tools and relevant functional tests of variants for analysis and
      interpretation of the resulting data. Ultimately, an optimal use of all those
      resources may improve patient care and therapeutic decision-making.

PMID- 29580111
TI  - The African American Eye Disease Study: Design and Methods.
AB  - PURPOSE: To describe the study design, operational and recruitment strategies,
      procedures, and baseline characteristics of the African American Eye Disease
      Study (AFEDS), a population-based assement of the prevalence of visual
      impairment, ocular disease, visual function, and health-related quality of life
      in African Americans. METHODS: This population-based, cross-sectional study
      included over 6000 African Americans 40 years and older residing in and around
      Inglewood, California. A detailed interview and eye examination was performed on
      each eligible participant. The interview included an assessment of demographic,
      behavioral, and ocular risk factors and health-related and vision-related quality
      of life. The eye examination included measurements of visual acuity, intraocular
      pressure, visual fields; fundus and optic disc photography; a detailed anterior
      and posterior segment examination; and measurements of blood pressure,
      glycosylated hemoglobin levels, and blood glucose levels. RESULTS: The AFEDS
      cohort includes more than 6000 participants that have completed a home
      questionnaire and a comprehensive eye examination. The majority of participants
      were female (63%), the average (+/- standard deviation) overall age was 60.9 (+/
      11.3). Participants are mostly working (40%) or retired (41%), non-smoking (57%),
      partial drinking (54%), and with at least some college education (38%). A trust
      development recruitment strategy was refined in order to overcome challenges in
      study participation. CONCLUSION: The AFEDS is the largest epidemiologic eye study
      among African Americans to date. The AFEDS cohort will provide information about
      the prevalence and risk factors of ocular disease in the largest ophthalmologic
      study population of African Americans in the United States.

PMID- 29580112
TI  - Invasive Mammary Carcinoma With Mixed Invasive Papillary and Glycogen Rich Clear
      Cell Features.
AB  - Invasive papillary carcinoma (IPC) and glycogen-rich clear cell carcinoma (GRCCC)
      are rare primary breast carcinomas. IPC typically have favorable prognosis,
      whereas the prognosis of GRCCC is less established. We report a unique case of
      high-grade invasive mammary carcinoma with mixed IPC and GRCCC features. We
      review the imaging and pathologic features and discuss prognosis of these unusual
      breast cancer subtypes.

PMID- 29580113
TI  - Platelet biomechanics, platelet bioenergetics, and applications to clinical
      practice and translational research.
AB  - The purpose of this review is to explore the relationship between platelet
      bioenergetics and biomechanics and how this relationship affects the clinical
      interpretation of platelet function devices. Recent experimental and
      technological advances highlight platelet bioenergetics and biomechanics as
      alternative avenues for collecting clinically relevant data. Platelet
      bioenergetics drive energy production for key biomechanical processes like
      adhesion, spreading, aggregation, and contraction. Platelet function devices like
      thromboelastography, thromboelastometry, and aggregometry measure these
      biomechanical processes. Platelet storage, stroke, sepsis, trauma, or the
      activity of antiplatelet drugs alters measures of platelet function. However, the
      specific mechanisms governing these alterations in platelet function and how they
      relate to platelet bioenergetics are still under investigation.

PMID- 29580114
TI  - Athletes and Supplements: Prevalence and Perspectives.
AB  - In elite sport, where opponents are evenly matched, small factors can determine
      the outcome of sporting contests. Not all athletes know the value of making wise
      nutrition choices, but anything that might give a competitive edge, including
      dietary supplements, can seem attractive. Between 40% and 100% of athletes
      typically use supplements, depending on the type of sport, level of competition,
      and the definition of supplements. However, unless the athlete has a nutrient
      deficiency, supplementation may not improve performance and may have a
      detrimental effect on both performance and health. Dietary supplements are
      classified as a subcategory of food, so manufacturers are not required to provide
      evidence of product safety and efficacy, nor obtain approval from regulatory
      bodies before marketing supplements. This creates the potential for health risks,
      and serious adverse effects have been reported from the use of some dietary
      supplements. Athletes who compete in sports under an anti-doping code must also
      realize that supplement use exposes them to a risk of ingesting banned substances
      or precursors of prohibited substances. Government systems of regulations do not
      include specific laboratory testing for banned substances according to the WADA
      list, so a separate regulatory framework to evaluate supplements for their risk
      of provoking a failed doping test is needed. In the high-performance culture
      typical of elite sport, athletes may use supplements regardless of possible
      risks. A discussion around medical, physiological, cultural, and ethical
      questions may be warranted to ensure that the athlete has the information needed
      to make an informed choice.

PMID- 29580116
TI  - Novel Surgical Techniques in Guided Bone Regeneration.

PMID- 29580115
TI  - Comparison of four methods to assess high-on platelet reactivity under P2Y12
      receptor inhibitor.
AB  - P2Y12 receptor inhibitors are antiplatelet agents commonly prescribed in the
      treatment of coronary artery disease. Their efficacy can be limited by high on
      treatment platelet reactivity (HPR), which can be evaluated by different
      biological assays. Most commonly, HPR is evaluated by flow cytometric vasodilator
      stimulated phosphoprotein-phosphorylation (VASP-P) assay, which can be time
      consuming. To evaluate the potential interest of novel technologies, we compared
      four different assays. Ninety patients receiving P2Y12 inhibitors were included.
      Four technologies were evaluated: the current standard test measuring VASP-P by
      flow cytometry, the historical reference test based on light transmittance
      aggregation (LTA), and two relatively novel techniques: whole blood multiple
      electrode aggregometry (MEA) and platelet function analyzer (PFA), which are less
      time consuming. The three latter tests were compared with the VASP-P assay as a
      reference using receiver operating characteristics (ROC) analysis: LTA has an
      excellent comparability with the VASP test (ROC AUC > 0.9); the other two tests
      (multiplate and PFA) have only satisfactory comparability (ROC AUC around 0.7)
      and therefore may not replace the VASP "gold standard" test, if importance is
      attached to a quantitative assessment of the substitution parameter of VASP.
      Nevertheless, if a binary approach of the anti-aggregation result is sought, then
      one can conclude that the three tests are equivalent since Cohen's kappa
      coefficients are very close for the three tests (k = 0.548 for LTA; k = 0.554 for
      MEA; k = 0.570 for PFA/P2Y), and a similar proportion of patients are
      misclassified (15% for LTA, 14% for MEA, and 13.6% for PFA). Discriminant factor
      analysis using all the parameters provided by each test did not improve the
      diagnostic performance of MEA or PFA. In conclusion, only LTA shows a good
      comparability to the VASP assay using ROC curve analysis, probably because
      misclassified patients have results close to the cutoff values. All three tests
      have moderate agreement regarding the classification of patients as responders to
      P2Y12 inhibition.

PMID- 29580117
TI  - Evidence for panmixia despite barriers to gene flow in the hooked mussel,
      Ischadium recurvum (Mytilidae; Brachidontinae) along the North American
      coastline.
AB  - The discovery of phylogeographic patterns within broadly distributed marine
      species can be particularly challenging because absolute physical barriers to
      dispersal can be inconspicuous. Genetic boundaries often lie where ocean currents
      meet, forming sharp physical and ecological gradients, which may act as barriers
      to successful migrants. In eastern North America, coastal species often show
      phylogeographic differentiation associated with two recognized genetic barriers:
      the Gulf/Atlantic and the Virginia/Carolina discontinuities. We examined 185
      specimens of the intertidal hooked mussel Ischadium recurvum collected from 15
      locations along the eastern coastline of North America to examine
      phylogeographic, migration and historical demographic patterns associated climate
      change associated with Pleistocene glacial patterns. Hypothesis testing using
      Bayes factors in Migrate-n rejected the presence of phylogeographic breaks
      consistent with either maritime discontinuity and favoured a panmictic population
      model. The migration rate from the Gulf to the Atlantic was approximately three
      times higher than the migration from the Atlantic to the Gulf whereas the
      Carolina-Virginia migration rates were nearly equal. The summary statistics
      (Tajima's D, Fu's Fs) were significant and the demographic analyses (mismatch
      distributions, Bayesian skyline plot) were consistent with patterns of population
      expansion following glacial retreat during the Pleistocene epoch.

PMID- 29580118
TI  - Invasive Solid Papillary Carcinoma of the Nipple With Pagetoid Extension and
      Nodal Metastasis.
AB  - We report a case of invasive solid papillary carcinoma (SPC) of the nipple with
      Pagetoid extension to the skin and lymph node metastasis. SPC is an uncommon
      primary breast cancer accounting for less than 1% of all breast cancers. Only 2
      cases occurring in the nipple have been reported. However, both cases were
      without Pagetoid extension or lymph node metastasis. The presently reported tumor
      consisted of irregularly shaped solid cell nests with delicate fibrovascular
      cores. The tumor cells had round nuclei with low-grade atypia and eosinophilic
      cytoplasm. Neuroendocrine differentiation was confirmed by immunohistochemical
      positivity for CD56, synaptophysin, and chromogranin A. Immunohistochemistry also
      confirmed the absence of myoepithelial cells around the tumor cell nests.
      Therefore, a diagnosis of invasive SPC was made. Additionally, tumor cell
      deposits in the intramammary and axillary lymph nodes were identified, and these
      deposits had the same histological characteristics as the invasive SPC of the
      nipple. The invasiveness of SPC can be difficult to determine. However, the tumor
      cell nests in the current case exhibited a retraction artifact, which is known to
      be associated with invasive carcinoma and a poor prognosis, as well as
      morphological patterns that have been previously identified as characteristic of
      invasive SPC. Although SPC is widely recognized as having a favorable outcome,
      the existence of exceptionally aggressive cases occurring in the nipple must be
      recognized. Additional cases of invasive SPC of the nipple are needed to analyze
      the clinicopathological correlation.

PMID- 29580119
TI  - A nationwide cohort study of the role of CHADS2 score in predicting lower
      extremity amputation and death among patients with peripheral arterial occlusive
      disease.
AB  - OBJECTIVES: The current study aimed to explore whether the CHADS2 score was
      predictive of lower extremity amputation (LEA) and death in people with
      peripheral arterial occlusive disease (PAOD). METHODS: This nationwide cohort
      came from Taiwan, with 16,888 PAOD patients, from 2000 through 2011, extracted
      from the Longitudinal Health Insurance Database 2000. Cox proportional hazard
      regression models were employed to identify the LEA and mortality risk according
      to CHADS2 score. The discriminatory properties of the score in predicting the
      outcomes were quantified by the area under the receiver operating characteristic
      curve (AUROC) and the Cox C-index. RESULTS: The AUROC of the CHADS2 score in
      predicting LEA and death were 0.75 (95% CI = 0.73-0.77) and 0.70 (95% CI = 0.69
      0.71), respectively. The CHADS2 score had an acceptable stratification capacity
      for LEA (C-index = 0.79) and death (C-index = 0.76) based on Cox-regression
      analysis. CONCLUSIONS: This study correlates the CHADS2 score with risk of
      developing LEA and death in patients with PAOD. The acceptable discriminative
      power of the score diversifies its predictive role in this population.

PMID- 29580120
TI  - Placental growth factor as a predictor of the efficacy of tadalafil treatment for
      fetal growth restriction.
AB  - PURPOSE: We recently demonstrated the efficacy of tadalafil treatment for fetal
      growth restriction (FGR). This study aimed to evaluate the utility of serum
      placental growth factor (PlGF) level for predicting the efficacy of tadalafil for
      the treatment of FGR. MATERIALS AND METHODS: The correlations between serum level
      of PlGF and fetal growth velocity were retrospectively assessed in nine pregnant
      women receiving tadalafil for FGR before 30 weeks' gestation. RESULTS: Median
      gestational age was 26 weeks (range 26-28 weeks), and median deviation of
      estimated fetal weight from standard weight was -2.1 standard deviations (SD) (
      2.2 to -1.9 SD) at the beginning of tadalafil treatment. The median serum PlGF
      level was 227 pg/ml (40.2-427.0 pg/ml) before tadalafil treatment and 278 pg/ml
      (66.2-729.5 pg/ml) more than 2 weeks after initiation of tadalafil treatment
      (median gestational week at measurement of PlGF after treatment, 33 weeks [28-33
      weeks]). The median fetal growth velocity from enrollment to birth was 17.5 g/day
      (12.1-20.3 g/day). Maternal serum PlGF levels were increased after tadalafil
      treatment in all nine cases (median increase in PlGF, 73.1 pg/ml [26.0-281.5
      pg/ml]). Notably, maternal serum PlGF level before tadalafil treatment
      significantly correlated with fetal growth velocity (R2 = 0.63, p < .01).
      CONCLUSIONS: Tadalafil treatment may increase maternal serum PlGF levels. Our
      results suggest that maternal serum PlGF levels can be used as a predictor of the
      efficacy of tadalafil treatment for FGR.

PMID- 29580122
TI  - "Comparison of Adjacent Segment Degeneration After Non-Rigid Fixation System and
      Posterior Lumbar Interbody Fusion for Single-Level Lumbar Disc Herniation: A New
      Method of MRI Analysis of Lumbar Nucleus Pulposus Volumen".

PMID- 29580121
TI  - Depletion of reactive oxygen species induced by chlorogenic acid triggers
      apoptosis-like death in Escherichia coli.
AB  - Chlorogenic acid (CGA) is a phenolic compound with various health-promoting
      properties, including antioxidant effects and a wide range of antibacterial
      activities. However, the antibacterial mechanism remains unclear. We investigated
      the underlying mode of action of CGA against Escherichia coli, which shows
      bacterial apoptosis-like death. Cells treated with CGA showed apoptotic features
      such as membrane depolarisation, caspase-like protein expression, increased
      intracellular Ca2+ levels, phosphatidylserine externalisation, and DNA
      fragmentation. In contrast to common bacterial apoptosis-like death, which is
      caused by reactive oxygen species (ROS) accumulation, CGA depleted intracellular
      ROS. Because ROS are important intracellular signalling molecules, and ROS
      depletion may affect bacterial intracellular signalling pathways, leading to cell
      death. To determine whether deficiencies in intracellular ROS cause apoptosis
      like death, the cells were treated with H2O2 after CGA treatment. H2O2 restored
      depleted intracellular ROS levels to similar levels as in untreated cells, and
      cell viability was increased compared to CGA-treated cells. Moreover, apoptotic
      features were attenuated in H2O2 post-treated cells. These results demonstrate
      that CGA induces bacterial apoptosis in E. coli and intracellular ROS depletion
      is a core regulator in the progression of bacterial apoptosis-like death.

PMID- 29580123
TI  - Ethnic and racial difference in Helicobacter pylori infection in patients with
      immune thrombocytopenia treated at a major urban medical center.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disorder with a complex
      immunopathology and pathogenesis characterized by thrombocytopenia and bleeding
      manifestations. The disorder is separated into primary (idiopathic) ITP and
      secondary ITP, when associated with other immune or lymphoproliferative disorders
      and certain chronic infections. Helicobacter pylori (H. pylori) is a recognized
      bacterial cause of ITP. In regions with high prevalence of infection, bacterial
      eradication has resulted in improvement in platelet count. However, the
      prevalence of H. pylori infection and response to antimicrobial therapy in North
      American ITP patients is reportedly low. We evaluated the prevalence of H. pylori
      infection in ITP patients diagnosed and treated at a large urban medical center.
      Eighty-two patients were screened for H. pylori, by stool antigen (n = 54), H.
      pylori breath test (n = 11), and H. pylori antibodies (n = 16), of which 15
      (18.3%) were white non-Hispanic (WNH), 55 (67%) Hispanic (H), 8 (9.8%) Asian (A),
      and 4 (4.9%) African-American (AA). Of the screened patients, 36/82 (43.9%)
      tested positive for H. pylori. The prevalence of H. pylori infection within the
      represented ethnic groups was 2/15 (13%) WNH, 29/55 (52.7%) H, 3/8 (37.5%) A, and
      2/4 (50%) AA. There was a significant difference in prevalence of infection
      comparing WNH and H patients (p = 0.007). There were 36 treated patients, with H.
      pylori eradication documented in 26 patients. Fifteen of the 26 patients were
      evaluable for response with 8 of 15 (53%) having clinical responses, 6 complete
      responses, and 2 partial responses. Our study demonstrates an increased
      prevalence of H. pylori infection in the Hispanic ITP population with a
      reasonable platelet response among patients with H. pylori eradication.

PMID- 29580124
TI  - De-epithelialized turnover dorsal flap for coverage of finger injuries: a
      modified technique.

PMID- 29580125
TI  - Familial bilateral congenital absence of the flexor pollicis longus.

PMID- 29580126
TI  - Long-Standing Ulcerative Colitis May Trigger a Multilineage Cancerization Field.
AB  - Longstanding/relapsing inflammation characterizing ulcerative colitis (UC) has
      been associated to an increased risk of colon mucosa neoplastic transformation.
      We describe the clinicopathological features of a UC-related poorly
      differentiated neuroendocrine carcinoma coexisting with a conventional
      adenocarcinoma. This case supports UC as a multilineage cancerization field.

PMID- 29580127
TI  - Epithelial sodium channel blockade and new beta-ENaC polymorphisms among
      normotensive and hypertensive adult Nigerians.
AB  - We sought to determine the effect of amiloride on blood pressure (BP) and the
      presence of polymorphisms of the beta-subunit of the epithelial sodium channel
      (ENaC) among normotensive (NT) and hypertensive (HT) Nigerians. Healthy
      volunteers-47 NT and 53 age-matched HT were recruited after giving informed
      consent. Subjects were salt-loaded with 200 mmol of NaCl daily for 5 days.
      Following a week washout period, salt-loading was repeated in addition to the
      administration of 5 mg amiloride daily for five days. Blood pressure, plasma and
      urine electrolytes were measured at baseline, after salt-loading and after salt
      loading plus amiloride. PCR amplicons were sequenced for beta-ENaC polymorphisms.
      Salt-loading led to a significant increase (p < 0.05) in SBP among NT and HT and
      in DBP (p < 0.001) only among HT. Amiloride reduced SBP and DBP to below baseline
      levels in NT (p < 0.05) and HT (p < 0.001) subjects. Five of the subjects had the
      beta-T594M polymorphism, HT 3/53; NT 2/47 (p = 0.75). Four previously unreported
      beta-ENaC mutations were recorded: E632V and E636V, respectively, among two HT
      subjects, D638Y in another HT and L628Q in one NT subject. We showed the presence
      of beta-ENaC polymorphisms among our populace and the possible usefulness of
      amiloride as a single antihypertensive among Nigerians.

PMID- 29580128
TI  - Breast cancer lung metastasis: Molecular biology and therapeutic implications.
AB  - Distant metastasis accounts for the vast majority of deaths in patients with
      cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving
      bone, liver, lung, and brain. Breast cancer can be divided into different
      subtypes based on gene expression profiles, and different breast cancer subtypes
      show preference to distinct organ sites of metastasis. Luminal breast tumors tend
      to metastasize to bone while basal-like breast cancer (BLBC) displays a lung
      tropism of metastasis. However, the mechanisms underlying this organ-specific
      pattern of metastasis still remain to be elucidated. In this review, we will
      summarize the recent advances regarding the molecular signaling pathways as well
      as the therapeutic strategies for treating breast cancer lung metastasis.

PMID- 29580129
TI  - Bidirectional influence of amygdala beta1-adrenoceptors blockade on cannabinoid
      signaling in contextual and auditory fear memory.
AB  - The basolateral amygdala (BLA) is a major target and modulator of stress and has
      a critical role in the neural circuitry presenting learned fear behaviors. On the
      other hand, both the endocannabinoid and noradrenergic systems may be involved in
      regulating the stress responses, fear, and anxiety. Considering the
      aforementioned, we have investigated the involvement of the BLA beta1
      adrenoceptors in conditioned fear responses induced by ACPA, a CB1 receptor
      (CB1R) agonist. In adult male NMRI mice, freezing responses to context and cue
      were measured using a Pavlovian fear conditioning apparatus. Pre-training intra
      BLA microinjection of xamoterol (0.01 and 0.02 ug/mouse), a partial beta1
      adrenoceptor agonist, or atenolol (0.5 ug/mouse), a beta1-adrenoceptor
      antagonist, decreased freezing behavior, which suggests an impairment of
      contextual and auditory fear retrieval. Similar results were found with pre
      training intraperitoneal administration of ACPA (0.5 mg/kg). A sub-threshold dose
      of xamoterol, infused into the BLA, decreased ACPA (0.005 and 0.05 mg/kg) effect
      on both memories, while atenolol increased ACPA response to the context at the
      middle dose and decreased ACPA response to the tone at the lower dose. It can be
      concluded that the blockade of BLA beta1-adrenoceptors differentially affects
      ACPA response on the contextual and auditory conditioned fear memories.

PMID- 29580130
TI  - Repeated intermittent oral amphetamine administration results in locomotor
      tolerance not sensitization.
AB  - BACKGROUND: The phenomenon of locomotor sensitization to injected amphetamine is
      well-characterised. The increased locomotor activity found acutely is enhanced
      with repeated intermittent treatment. This effect arises due to
      hypersensitization of the dopaminergic system and is linked to drug addiction. A
      clinical population exposed to chronic repeated intermittent amphetamine
      treatment, such as is found for attention deficit hyperactivity disorder (ADHD),
      may be expected to be more at risk of addiction following this treatment.
      However, evidence suggests the opposite may be true. This suggests the route of
      administration may determine the direction of effects. AIMS AND METHODS: We aimed
      to establish how an oral amphetamine treatment regimen, similar to that used in
      ADHD, impacts on locomotor activity, specifically whether tolerance or
      sensitization would arise. Healthy hooded Lister rats were given amphetamine (2
      mg/kg, 5 mg/kg and 10 mg/kg) or a vehicle solution once daily for 4 weeks with a
      5 day on, 2 day off schedule. Locomotor activity was measured on the first day of
      treatment to establish the acute effects and on the final day of treatment to
      examine the chronic effects. RESULTS: As expected, acute doses of amphetamine
      increased locomotor activity, although this only reached statistical significance
      for the 5 mg/kg and 10 mg/kg doses. By contrast, after chronic treatment, animals
      administered these doses showed reduced activity indicating drug tolerance rather
      than sensitization had occurred. CONCLUSION: We suggest that the route of
      administration used in ADHD, which results in more stable and longer duration
      drug levels in the blood, results in tolerance rather than sensitization and that
      this effect could explain the reduced likelihood of substance addiction in those
      treated with psychostimulants for ADHD.

PMID- 29580131
TI  - How Do Allied Health Professionals Define and Apply Equity When Making Resource
      Allocation Decisions?
AB  - An ethnographic study was conducted in 2 stages to understand how allied health
      professionals define and apply equity when making resource allocation decisions.
      Participants were allied health managers and clinicians from Victoria, Australia.
      Stage 1 included 4 semi-structured forums that incorporated real-life case
      studies, group discussions, and hypothetical scenarios. The project's steering
      committee began a thematic analysis during post-forum discussions. Stage 2
      included a key stakeholder working party that further discussed the concept of
      equity. The forum recordings were transcribed verbatim, and a detailed thematic
      analysis ensured the initial thematic analysis was complete. Several domains of
      equity were discussed. Participants would readily identify that equity was a
      consideration when making resource decisions but were generally silent for a
      prolonged period when prompted to identify what they meant when using this term.
      The findings indicate that asking allied health professionals to directly state
      how they define and apply equity to their decision-making could be too difficult
      a task, as this did not elicit rich and meaningful discussions. Future research
      should examine individual domains of equity when applied to resource allocation
      decisions.

PMID- 29580132
TI  - Learning "Math on the Move": Effectiveness of a Combined Numeracy and Physical
      Activity Program for Primary School Children.
AB  - BACKGROUND: Physically active learning that combines physical activity with core
      curriculum areas is emerging in school-based health interventions. This study
      investigates the effectiveness of learning an important numeracy skill of times
      tables (TT) while concurrently engaging in aerobic activity compared with a
      seated classroom approach. METHODS: Grade-4 primary school students were randomly
      allocated to physical activity (P) or classroom (C) groups and received the
      alternate condition in the following term. P group received moderate to vigorous
      exercise (20 min, 3 times per week, 6 wk) while simultaneously learning selected
      TT. C group received similar learning, but seated. Changes in TT accuracy,
      general numeracy, aerobic fitness, and body mass index were assessed. Data were
      expressed as mean (SEM) and between-condition effect size (ES; 95% confidence
      interval). RESULTS: Participants [N = 85; 55% male, 9.8 (0.3) y, 36.4%
      overweight/obese] improved similarly on TT in both conditions [C group: 2.2%
      (1.1%); P group: 2.5% (1.3%); ES = 0.03; -0.30 to 0.36; P = .86]. Improvement in
      general numeracy was significantly greater for P group than C group [C group:
      0.7% (1.2%); P group: 5.3% (1.4%); ES = 0.42; 0.08 to 0.75; P < .03]. An
      improvement in aerobic fitness for P group (P < .01) was not significantly
      greater than C group [C group: 0.8 (0.6); P group: 2.2 (0.5) mL.kg.min-1; ES =
      0.32; -0.01 to 0.66; P = .06]. Body mass index was unchanged. CONCLUSION:
      Combined movement with learning TT was effective. Physically active learning
      paradigms may contribute to meeting daily physical activity guidelines while
      supporting or even boosting learning.

PMID- 29580133
TI  - Time interval of revaccination with 23-valent pneumococcal polysaccharide vaccine
      more than 5 years does not affect the immunogenicity and safety in the Japanese
      elderly.
AB  - In the previous study, revaccination with 23-valent pneumococcal polysaccharide
      vaccine (PPSV23) in a total of 161 elderly subjects (>=70 years of age) who had
      received the initial vaccination at least 5 years before (range: 5 to11 years)
      showed an acceptable safety profile and induction of immune responses to the
      serotypes in PPSV23. The optimal interval between the initial vaccination and
      revaccination with PPSV23 is of interest to protect elderly from pneumococcal
      disease over the long-term. In this post-hoc analysis, we analyzed that the
      immunogenicity and safety of revaccination with PPSV23 by time interval after the
      initial vaccination. The level of serotype-specific immunoglobulin G (IgG)
      geometric mean concentrations (GMCs) and opsonophagocytic killing activity (OPA)
      geometric mean titers (GMTs) at 4 weeks after revaccination with PPSV23 in each
      subgroup based on time interval (5, 6, 7, 8 and 9-11 years) after the initial
      vaccination were comparable to those after the primary vaccination and vaccine
      induced serotype-specific IgG and OPA levels were similar regardless of the time
      interval after the initial vaccination. There was no difference in the safety
      profiles among the subgroups. In conclusion, administration of a second dose of
      PPSV23 at least 5 years after the initial vaccination was immunogenic and well
      tolerated in the elderly >=70 years of age regardless of the time interval after
      the initial vaccination.

PMID- 29580134
TI  - Low- and High-Volume Water-Based Resistance Training Induces Similar Strength and
      Functional Capacity Improvements in Older Women: A Randomized Study.
AB  - BACKGROUND: Water-based resistance training (WRT) has been indicated to promote
      strength gains in elderly population. However, no study has compared different
      training strategies to identify the most efficient one. The aim of this study was
      to compare the effects of 3 WRT strategies on the strength and functional
      capacity of older women. METHODS: In total, 36 women were randomly allocated to
      training groups: simple set of 30 seconds [1 * 30s; 66.41 (1.36) y; n = 12],
      multiple sets of 10 seconds [3 * 10s; 66.50 (1.43) y; n = 11], and simple set of
      10 seconds [1 * 10s; 65.23 (1.09) y; n = 13]. Training lasted for 12 weeks. The
      maximal dynamic strength (in kilograms) and muscular endurance (number of
      repetitions) of knee extension, knee flexion, elbow flexion, and bench press, as
      well as functional capacity (number of repetitions), were evaluated. RESULTS: All
      types of training promoted similar gains in maximal dynamic strength of knee
      extension and flexion as well as elbow flexion. Only the 1 * 30s and 1 * 10s
      groups presented increments in bench press maximal strength. All 3 groups showed
      increases in muscular endurance in all exercises and functional capacity.
      CONCLUSIONS: WRT using long- or short-duration simple sets promotes the same
      gains in strength and functional capacity in older women as does WRT using
      multiple sets.

PMID- 29580135
TI  - Understanding the Nature of Measurement Error When Estimating Energy Expenditure
      and Physical Activity via Physical Activity Recall.
AB  - BACKGROUND: The National Health and Nutrition Examination Survey physical
      activity questionnaire (PAQ) is used to estimate activity energy expenditure
      (AEE) and moderate to vigorous physical activity (MVPA). Bias and variance in
      estimates of AEE and MVPA from the PAQ have not been described, nor the impact of
      measurement error when utilizing the PAQ to predict biomarkers and categorize
      individuals. METHODS: The PAQ was administered to 385 adults to estimate AEE
      (AEE:PAQ) and MVPA (MVPA:PAQ), while simultaneously measuring AEE with doubly
      labeled water (DLW; AEE:DLW) and MVPA with an accelerometer (MVPA:A). RESULTS:
      Although AEE:PAQ [3.4 (2.2) MJ.d-1] was not significantly different from AEE:DLW
      [3.6 (1.6) MJ.d-1; P > .14], MVPA:PAQ [36.2 (24.4) min.d-1] was significantly
      higher than MVPA:A [8.0 (10.4) min.d-1; P < .0001]. AEE:PAQ regressed on AEE:DLW
      and MVPA:PAQ regressed on MVPA:A yielded not only significant positive
      relationships but also large residual variances. The relationships between AEE
      and MVPA, and 10 of the 12 biomarkers were underestimated by the PAQ. When
      compared with accelerometers, the PAQ overestimated the number of participants
      who met the Physical Activity Guidelines for Americans. CONCLUSIONS: Group-level
      bias in AEE:PAQ was small, but large for MVPA:PAQ. Poor within-participant
      estimates of AEE:PAQ and MVPA:PAQ lead to attenuated relationships with
      biomarkers and misclassifications of participants who met or who did not meet the
      Physical Activity Guidelines for Americans.

PMID- 29580137
TI  - Natural Diversity in Heat Resistance of Bacteria and Bacterial Spores: Impact on
      Food Safety and Quality.
AB  - Heat treatments are widely used in food processing often with the aim of reducing
      or eliminating spoilage microorganisms and pathogens in food products. The
      efficacy of applying heat to control microorganisms is challenged by the natural
      diversity of microorganisms with respect to their heat robustness. This review
      gives an overview of the variations in heat resistances of various species and
      strains, describes modeling approaches to quantify heat robustness, and addresses
      the relevance and impact of the natural diversity of microorganisms when
      assessing heat inactivation. This comparison of heat resistances of
      microorganisms facilitates the evaluation of which (groups of) organisms might be
      troublesome in a production process in which heat treatment is critical to
      reducing the microbial contaminants, and also allows fine-tuning of the process
      parameters. Various sources of microbiological variability are discussed and
      compared for a range of species, including spore-forming and non-spore-forming
      pathogens and spoilage organisms. This benchmarking of variability factors gives
      crucial information about the most important factors that should be included in
      risk assessments to realistically predict heat inactivation of bacteria and
      spores as part of the measures for controlling shelf life and safety of food
      products.

PMID- 29580138
TI  - Stability and Stabilization of Enzyme Biosensors: The Key to Successful
      Application and Commercialization.
AB  - Fifty-five years have passed and more than 100,000 articles have been published
      since the first report of an electrochemical enzyme biosensor. However, very few
      biosensors have reached practical application and commercialization. The bulk of
      the research effort has been on increasing sensitivity and selectivity. In
      contrast, the number of publications dealing with stability or stabilization of
      enzyme biosensors is very small. Here, we critically review enzyme stabilization
      strategies as well as the progress that has been done in the past 20 years with
      respect to enzyme biosensor stabilization. Glucose oxidase, lactate oxidase,
      alcohol oxidase, and xanthine oxidase are the focus of this review because of
      their potential applications in food. The inconsistency in reporting biosensor
      stability was identified as a critical hurdle to research progress in this area.
      Fundamental questions that remain unanswered are outlined.

PMID- 29580139
TI  - Use of Natural Selection and Evolution to Develop New Starter Cultures for
      Fermented Foods.
AB  - The fermented foods industry is constantly seeking new starter cultures to deal
      with changing consumer preferences and new fermentation processes. New cultures
      can either be composed of strains isolated from nature or improved derivatives of
      existing isolates. A variety of techniques involving natural selection and
      evolution are available to enhance the performance of existing strains, including
      the isolation of mutants with desired properties, adaptive laboratory evolution,
      genome shuffling, and genome editing. Numerous examples of traits that can be
      improved are provided. These include resistance to bacteriophages; the secretion
      of glucose to increase sweetness; the production of vitamins, antifungal
      compounds, bacteriocins, texture, or aroma; enhancement of acidification rates
      and acid tolerance; and elimination of biofilm formation. Careful consideration
      is required to ensure the developed strains are suitable for the desired purpose,
      as some approaches may lead to regulatory concerns.

PMID- 29580136
TI  - Milk Glycans and Their Interaction with the Infant-Gut Microbiota.
AB  - Human milk is a unique and complex fluid that provides infant nutrition and
      delivers an array of bioactive molecules that serve various functions. Glycans,
      abundant in milk, can be found as free oligosaccharides or as glycoconjugates.
      Milk glycans are increasingly linked to beneficial outcomes in neonates through
      protection from pathogens and modulation of the immune system. Indeed, these
      glycans influence the development of the infant and the infant-gut microbiota.
      Bifidobacterium species commonly are enriched in breastfed infants and are among
      a limited group of bacteria that readily consume human milk oligosaccharides
      (HMOs) and milk glycoconjugates. Given the importance of bifidobacteria in infant
      health, numerous studies have examined the molecular mechanisms they employ to
      consume HMOs and milk glycans, thus providing insight into this unique enrichment
      and shedding light on a range of translational opportunities to benefit at-risk
      infants.

PMID- 29580140
TI  - Uptake of Engineered Nanoparticles by Food Crops: Characterization, Mechanisms,
      and Implications.
AB  - With the rapidly increasing demand for and use of engineered nanoparticles (NPs)
      in agriculture and related sectors, concerns over the risks to agricultural
      systems and to crop safety have been the focus of a number of investigations.
      Significant evidence exists for NP accumulation in soils, including potential
      particle transformation in the rhizosphere and within terrestrial plants,
      resulting in subsequent uptake by plants that can yield physiological deficits
      and molecular alterations that directly undermine crop quality and food safety.
      In this review, we document in vitro and in vivo characterization of NPs in both
      growth media and biological matrices; discuss NP uptake patterns,
      biotransformation, and the underlying mechanisms of nanotoxicity; and summarize
      the environmental implications of the presence of NPs in agricultural ecosystems.
      A clear understanding of nano-impacts, including the advantages and
      disadvantages, on crop plants will help to optimize the safe and sustainable
      application of nanotechnology in agriculture for the purposes of enhanced yield
      production, disease suppression, and food quality.

PMID- 29580141
TI  - Lactic Acid Bacteria Exopolysaccharides in Foods and Beverages: Isolation,
      Properties, Characterization, and Health Benefits.
AB  - Exopolysaccharides produced by lactic acid bacteria are a diverse group of
      polysaccharides produced by many species. They vary widely in their molecular,
      compositional, and structural characteristics, including mechanisms of synthesis.
      The physiochemical properties of these polymers mean that they can be exploited
      for the sensorial and textural enhancement of a variety of food and beverage
      products. Traditionally, lactic acid bacteria exopolysaccharides have an
      important role in fermented dairy products and more recently are being applied
      for the improvement of bakery products. The health benefits that are continually
      being associated with these polysaccharides enable the development of dual
      function, added-value, and clean-label products. To fully exploit and understand
      the functionality of these exopolysaccharides, their isolation, purification, and
      thorough characterization are of great importance. This review considers each of
      the above factors and presents the current knowledge on the importance of lactic
      acid bacteria exopolysaccharides in the food and beverage industry.

PMID- 29580142
TI  - A rare case of multicentric castleman's disease transforms into multiple myeloma
      and its successful treatment.
AB  - Multicentric Castleman's disease (MCD) is a rare kind of lymphoproliferative
      disorder characterized by systemic problems such as frequent fever, fatigue and
      weight loss with angiofollicular lymph node hyperplasia. However, unlike
      unicentric Castleman's disease (UCD) with long-time survival by surgery and local
      radiotherapy, MCD remains poor prognosis due to no well-defined optimal treatment
      strategies and high risk of developing malignances especially lymphoma. We
      reported a case of MCD who received chemotherapy by ECHOP with unsatisfactory
      outcome and then oral administration with thalidomide combined with prednisone
      without disease progression after therapy. After 3 y, his MCD turned into
      multiple myeloma (MM) and accompanied by obvious response to combination of
      thalidomide with prednisone. Nowadays, there is no standard of therapy yet
      established for MCD. We successfully treated one such patient and found
      thalidomide based therapy may have a significant effect on MCD. We also proposed
      further researches with therapeutic potential about thalidomide for MCD.

PMID- 29580143
TI  - MiR-135a-5p represses proliferation of HNSCC by targeting HOXA10.
AB  - OBJECTIVES: This research aimed to explore the role of miR-135a-5p in head and
      neck squamous cell carcinoma (HNSCC) cells and its influence on cell viability.
      Moreover, we aimed to compare effects of miR-135a-5p and miR-494 in HNSCC, which
      was found to repress HOXA10 expression in oral cancer. METHODS: The association
      between miR-135a-5p and HOXA10 was confirmed by green fluorescence protein
      reporter assay and qRT-PCR. The expression levels of HOXA10 in HNSCC cell lines
      (CAL-27, FaDu and NEC) were examined using western blot. The expression levels of
      HOXA10 in FaDu cells and CAL-27 cells were examined by western blot after
      transfection with miR-135a-5p mimics and miR-494 mimics. Colony formation assay
      and flow cytometry assay were respectively utilized to detect the proliferation
      and apoptosis of HNSCC cells after transfection with HOXA10 plasmids and HOXA10
      KO plasmids. In vitro tumor xenograft experiments were performed to analyze the
      inhibitive effect of miR-135a-5p on HOXA10 in BALA/c mice. RESULTS: HOXA10 was
      overexpressed in HNSCC cells, while miR-135a-5p was under-expressed. Therefore,
      low expression of HOXA10 lengthened disease-free survival time and overall
      survival time. MiR-135a-5p overexpression could inhibit HOXA10 expression by
      directly targeting HOXA10 3'UTR, and the inhibition was more effective than miR
      494. HOXA10 suppression inhibited proliferation and enhanced apoptosis of HNSCC
      cells. In vivo experiments showed that miR-135a-5p could decelerate the growth of
      tumor cells in mice by downregulating HOXA10 expression. CONCLUSION: MiR-135a-5p
      could repress HNSCC cells proliferation and enhance apoptosis by directly
      targeting HOXA10, implying miR-135a-5p's significance on HNSCC treatment.

PMID- 29580144
TI  - Natural dietary compound naringin prevents azoxymethane/dextran sodium sulfate
      induced chronic colorectal inflammation and carcinogenesis in mice.
AB  - : Naringin, a natural occurring flavonoid compound, enriches in citrus fruits. We
      aimed to evaluate the inhibitory effect of naringin on colitis and chronic
      inflammation-driven carcinogenesis. Male C57BL/6 mice were exposed to AOM/DSS to
      induce colorectal inflammation and carcinogenesis. Naringin by oral
      administration prevented AOM/DSS-induced ulcerative colitis and carcinogenesis
      without significant side effects. Naringin attenuated the severity of colitis and
      colorectal adenomas through inhibiting myeloid-derived suppressor cells (MDSCs),
      pro-inflammatory mediators GM-CSF/M-CSF, IL-6 and TNF-alpha and the NF-kappaB/IL
      6/STAT3 cascades in colorectal tissues. Naringin-treated mice exhibited
      normalized structures of colorectal tissues. Electron microscopy analysis showed
      the suppression of robust endoplasmic reticulum (ER) stress-induced autophagy.
      Naringin inhibited the secretion of the ER-spanning transmembrane proteins, such
      as GRP78 ATF6, IRE1alpha and activated PERK phosphorylated eIF-2alpha and complex
      of autophagosomes ATG3, ATG5, ATG7, ATG12, ATG16 and ATG16L1 in the colorectal
      mucosal cells. CONCLUSION: Naringin prevented colitis and colorectal
      carcinogenesis through suppressing robust ER stress-induced autophagy in
      colorectal mucosal cells. Naringin could develop a promising therapeutic agent
      for the prevention of ulcerative colitis and colorectal tumor.

PMID- 29580146
TI  - Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on
      Older Adults' Cardiovascular Profile: Part 2-Isotemporal Substitution Approach.
AB  - BACKGROUND: The aim of the study was to provide an isotemporal substitution model
      to predict how changes in physical behavior may affect the cardiovascular
      parameters (CVPs) of older adults. METHODS: Participants wore a thigh-mounted
      accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal
      artery was conducted using ultrasound. Isotemporal substitution was used to
      simulate the degree to which replacing 1 hour of physical behavior with another
      would affect CVP. RESULTS: Substitution of sedentary behavior with Standing and
      sporadic moderate- to vigorous-intensity physical activity (MVPA accumulated in
      bouts <10 min) would reduce resting heart rate [-6.20 beats per minute (-12.1 to 
      0.22) and -3.72 beats per minute (-7.01 to -0.44), respectively]. Substitution of
      sedentary behavior with light-intensity physical activity would reduce carotid
      artery diameter [-0.54 mm (-1.00 to -0.07)]. Substitution of Standing with
      sporadic MVPA would increase popliteal artery diameter [1.31 mm (0.11 to 2.51)].
      CONCLUSIONS: Our modeling suggests that an accumulation of MVPA bouts that are
      shorter than the recommended 10-minute minimum may still improve CVP, with lower
      intensity physical activity also influencing CVP. Our findings are a promising
      avenue for lifestyle interventions in older adults to reduce the aging effects on
      CVP for those who cannot engage or sustain sufficient MVPA.

PMID- 29580145
TI  - Ovarian dysgerminoma in pregnancy: A case report and literature review.
AB  - BACKGROUND: Dysgerminoma is an uncommon malignant tumor arising from the germ
      cells of the ovary. Its association with pregnancy is extremely rare; the
      incidence is about 0.2-1 per 100,000 pregnancies. Because of its infrequency,
      there are few recommendations regarding its management in pregnancy; therefore,
      it is important to discuss and summarize the treatment strategy. CASE: We
      presented a case of a 23-year-old pregnant woman with a large dysgerminoma
      originated from the right ovary, which had the unusual coincidence of being
      associated with an abdominal desmoid tumor simultaneously. We did not find any
      similar cases published in the PubMed database after 1947. A cesarean section was
      performed at 34 + 6 weeks gestation secondary to her abdominal pain worsening.
      The patient delivered a healthy boy and had fertility-preserving surgery,
      followed by 6 cycles of chemotherapy. This case is compared with 21 other
      reported cases of pure ovarian dysgerminoma in the literature to evaluate the
      clinical characteristics, feto-maternal compromise, treatment, long-term
      survival, and fertility outcome. CONCLUSION: The treatment strategy in women with
      ovarian dysgerminoma should be discussed and structured on an individual basis.
      If pregnancy is desired, surgical intervention undertaken in the second trimester
      seems to be the first choice. When chemotherapy is indicated, unless delivery can
      be accomplished within a few weeks of diagnosis, it should not necessarily be
      delayed until after delivery. Good reproductive function and high survival rate
      can be achieved in patients treated with conservative surgery and adjuvant
      chemotherapy.

PMID- 29580147
TI  - Early brain metastasis of advanced gastric cancer with a pathological complete
      response to neoadjuvant chemotherapy followed by surgery: A case report and
      literature review.
AB  - Advanced gastric cancer with a pathological complete response to neoadjuvant
      chemotherapy and surgery followed by early brain metastasis is rare. A 52-y-old
      male patient who was diagnosed with advanced gastric cancer (cT4N2M0, stage SHB).
      Radiological examinations after three cycles of preoperative chemotherapy with a
      modified FOLFOX6 (mFOLFOX6) regimen showed a partial response (PR) had been
      achieved. The patient underwent curative surgery consisting of proximal
      gastrectomy, and D2 lymph node dissection. The lack of abnormal gastric cancer
      cells in the primary lesion or lymph nodes confirmed a pathological complete
      response (pCR). Postoperative chemotherapy with oral S-1 was administrated.
      However, during the second cycles of postoperative chemotherapy, the patient
      experienced headaches, projectile vomiting and convulsion. Upon further
      examination, a tumor representing metastasis to the brain was recognized by
      cranial enhanced magnetic resonance imaging (MRI) examination and cytopathology
      of cerebrospinal fluid. In addition to documenting the case report, we reviewed
      the literature associated to features of metastatic brain malignancies that form
      from gastric cancer. In short, advanced gastric cancer patents achieved pCR after
      preoperative chemotherapy typically have good prognosis; however, great attention
      should be paid on detecting metastatic events.

PMID- 29580148
TI  - Can Exposure to Online Conversations About Death and Dying Influence Death
      Competence? An Exploratory Study Within an Australian Massive Open Online Course.
AB  - A Massive Open Online Course, Dying2Learn, was designed to foster community death
      conversations and strengthen community awareness of palliative care and death as
      a normal process. This exploratory study used a pre-post prospective design to
      determine if participation in Dying2Learn and exposure to online conversations
      about death and dying resulted in any significant influence on death competence
      in 134 participants who completed the Coping-with-Death-Scale both at the
      beginning and end of the course in 2016. Death competence refers to a range of
      attitudes and capabilities people have for dealing with death. Results at the end
      of the course indicated that engagement in Dying2Learn led to significant
      improvements in death competence scores over time (medium-to-large effect size).
      The positive impact was greater for those who completed more of the course, and
      effectiveness did not depend on sociodemographic characteristics. In conclusion,
      this study found that an online learning platform in the form of a Massive Open
      Online Course could engage community members in meaningful social discussion
      about death and dying, and that exposure to these conversations was beneficial
      for all participants regardless of previous exposure to death. Further
      exploration is required to determine whether this change in death competence will
      have an impact on participant's behavior in the community regarding death
      conversations and preparedness.

PMID- 29580150
TI  - Embodied Interaction Priority: Other's Body Part Affects Numeral-Space Mappings.
AB  - Traditionally, the spatial-numerical association of response codes (SNARC) effect
      was presented in two-choice condition, in which only one individual reacted to
      both even (small) and odd (large) numbers. Few studies explored SNARC effect in a
      social situation. Moreover, there are many reference frames involved in SNARC
      effect, and it has not yet been investigated which reference frame is dominated
      when two participants perform the go-nogo task together. In the present study, we
      investigated which reference frame plays a primary role in SNARC effect when
      allocentric and egocentric reference frames were consistent or inconsistent in
      social settings. Furthermore, we explored how two actors corepresent number-space
      mapping interactively. Results of the two experiments demonstrated that
      egocentric reference frame was at work primarily when two reference frames were
      consistent and inconsistent. This shows that body-centered coordinate frames
      influence number-space mapping in social settings, and one actor may represent
      another actor's action and tasks.

PMID- 29580149
TI  - A novel BRCA2 mutation in prostate cancer sensitive to combined radiotherapy and
      androgen deprivation therapy.
AB  - Genetic factors contribute to more than 40% of prostate cancer risk, and
      mutations in BRCA1 and BRCA2 are well-established risk factors. By using target
      capture-based deep sequencing to identify potential pathogenic germline
      mutations, followed by Sanger sequencing to determine the loci of the mutations,
      we identified a novel pathogenic BRCA2 mutation caused by a cytosine-to-guanine
      base substitution at position 4211, resulting in protein truncation
      (p.Ser1404Ter), which was confirmed by immunohistochemistry. Analysis of
      peripheral blood also identified benign polymorphisms in BRCA2 (c.7397T>C,
      p.Val2466Ala) and SRD5A2 (c.87G>C, p.Lys29Asn). Analysis of tumor tissues
      revealed seven somatic mutations in prostate tumor tissue and nine somatic
      mutations in esophageal squamous carcinoma tissue (single nucleotide
      polymorphisms, insertions, and deletions). Five-year follow-up results indicate
      that ADT combined with radiotherapy successfully treated the prostate cancer. To
      our knowledge, we are the first to report the germline BRCA2 mutation c.4211C>G
      (p.Ser1404Ter) in prostate cancer. Combined ADT and radiotherapy may be effective
      in treating other patients with prostate cancer caused by this or similar
      mutations.

PMID- 29580151
TI  - Effects of Facial Skin Smoothness and Blemishes on Trait Impressions.
AB  - People make trait inferences based on facial appearance, and these inferences
      guide social approach and avoidance. Here, we investigate the effects of textural
      features on trait impressions from faces. In contrast to previous work, which
      exclusively manipulated skin smoothness, we manipulated smoothness and the
      presence of skin blemishes independently (Study 1) and orthogonally (Study 2). We
      hypothesized that people are particularly sensitive to skin blemishes because
      blemishes potentially indicate poor health and the presence of an infectious
      disease. We therefore predicted that the negative effect of blemished skin is
      stronger than the positive effect of smoothed skin. The results of both studies
      are in line with this reasoning. Across ratings of trustworthiness, competence,
      maturity, attractiveness, and health, the negative influence of skin blemishes
      was stronger and more consistent than the positive influence of skin smoothness
      (Study 1). Moreover, the presence of skin blemishes diminished the positive
      effect of skin smoothness on attractiveness ratings (Study 2). In sum, both
      facial skin blemishes and facial skin smoothness influence trait impression, but
      the negative effect of blemished skin is larger and more salient than the
      positive effect of smooth skin.

PMID- 29580152
TI  - Epidemiology, risk factors, and clinical outcomes in severe microbial keratitis
      in South India.
AB  - PURPOSE: Here, we report risk factors associated with outcome in severe bacterial
      keratitis (BK), fungal keratitis (FK), and Acanthamoeba keratitis (AK) in India.
      METHODS: Prospective observational cohort study conducted in Aravind Eye
      Hospital, India. Adults presenting with severe microbial keratitis (MK) were
      enrolled (size >=3 mm) and followed to 21 days post-enrolment. Ulcer clinical
      features were recorded at presentation. Outcomes by final visit were classified
      as good (completely healed or reduced infiltrate size) or poor (enlarged
      infiltrate size, perforated, or surgery performed). RESULTS: Of 252 participants
      with severe MK, 191 had FK, 18 had AK, 19 had BK, 4 had mixed BK/FK, and 20 were
      microbiologically negative. Median age was 50 years (interquartile range [IQR]:
      37-60 years), 64% were male, 63% were agriculturalists, and 45% had no formal
      education. Corneal trauma occurred in 72%, and median symptom duration before
      presentation was 7 days (IQR: 5-15 days). Clinical features associated with FK
      were feathery margins (p < 0.001), raised profile (p = 0.039), or dry surface (p
      = 0.007). Hypopyon was more likely in BK (p = 0.001) and ring infiltrate in AK (p
      < 0.001). Ulcers with poor outcome (n = 106/214) were more likely to be larger
      (odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.30-2.05, p < 0.001),
      involve the posterior cornea at presentation (OR: 2.31, 95% CI: 1.16-4.59, p =
      0.017), involve Aspergillus sp. (OR: 3.23, 95% CI: 1.26-8.25, p = 0.014), or
      occur in females (OR: 2.04, 95% CI: 1.03-4.04, p = 0.04). Even after treatment,
      34% (n = 76/221) had severe visual impairment by the final visit. CONCLUSIONS:
      Severe MK occurred predominantly in agriculturalists post-corneal trauma and
      often had poor outcomes. Provision of community-based eyecare may allow earlier
      treatment and improve outcomes.

PMID- 29580153
TI  - Peripheral nerve injury increases contribution of L-type calcium channels to
      synaptic transmission in spinal lamina II: Role of alpha2delta-1 subunits.
AB  - Background Following peripheral nerve chronic constriction injury, the
      accumulation of the alpha2delta-1 auxiliary subunit of voltage-gated Ca2+
      channels in primary afferent terminals contributes to the onset of neuropathic
      pain. Overexpression of alpha2delta-1 in Xenopus oocytes increases the opening
      properties of Cav1.2 L-type channels and allows Ca2+ influx at physiological
      membrane potentials. We therefore posited that L-type channels play a role in
      neurotransmitter release in the superficial dorsal horn in the chronic
      constriction injury model of neuropathic pain. Results Whole-cell recording from
      lamina II neurons from rats, subject to sciatic chronic constriction injury,
      showed that the L-type Ca2+ channel blocker, nitrendipine (2 uM) reduced the
      frequency of spontaneous excitatory postsynaptic currents. Nitrendipine had
      little or no effect on spontaneous excitatory postsynaptic current frequency in
      neurons from sham-operated animals. To determine whether alpha2delta-1 is
      involved in upregulating function of Cav1.2 L-type channels, we tested the effect
      of the alpha2delta-1 ligand, gabapentin (100 uM) on currents recorded from
      HEK293F cells expressing Cav1.2/beta4/alpha2delta-1 channels and found a
      significant decrease in peak amplitude with no effect on control
      Cav1.2/beta4/alpha2delta-3 expressing cells. In PC-12 cells, gabapentin also
      significantly reduced the endogenous dihydropyridine-sensitive calcium current.
      In lamina II, gabapentin reduced spontaneous excitatory postsynaptic current
      frequency in neurons from animals subject to chronic constriction injury but not
      in those from sham-operated animals. Intraperitoneal injection of 5 mg/kg
      nitrendipine increased paw withdrawal threshold in animals subject to chronic
      constriction injury. Conclusion We suggest that L-type channels show an increased
      contribution to synaptic transmission in lamina II dorsal horn following
      peripheral nerve injury. The effect of gabapentin on Cav1.2 via alpha2delta-1 may
      contribute to its anti-allodynic action.

PMID- 29580155
TI  - Self-Compassion and the Self-Regulation of Exercise: Reactions to Recalled
      Exercise Setbacks.
AB  - Self-compassion facilitates health behavior self-regulation; few studies have
      examined self-compassion and exercise. This online, cross-sectional study
      investigated self-compassion's relationship with exercise self-regulation of an
      exercise setback. Adults (N = 105) who had experienced an exercise setback within
      the last 6 months completed baseline measures, recalled an exercise setback, and
      completed questionnaires assessing self-regulation in this context. Self
      compassion associated with self-determined motivations and exercise goal
      reengagement, and negatively related to extrinsic motivations, state rumination,
      and negative affect. Self-compassion predicted unique variance, beyond self
      esteem, in exercise goal reengagement, external regulation, state rumination, and
      negative affect experienced after an exercise setback. Self-compassion and self
      esteem had unique relationships with goal reengagement, state rumination, and
      situational motivation, while having a complementary relationship with negative
      affect. This research adds to the few studies that examine the role of self
      compassion in exercise self-regulation by examining how self-compassion and self
      esteem relate to reactions to a recalled exercise setback.

PMID- 29580156
TI  - Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer.
AB  - INTRODUCTION: Tissue sampling of gallbladder cancer (GBCa) is challenging because
      of the anatomy of the gallbladder. The aim of this study is to investigate the
      possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in
      addition to current diagnostic methods. METHODS: Thirty patients with GBCa were
      enrolled in this study. Cytological examination was performed in all patients.
      Using next generation sequencing (NGS), DNA isolated from the bile and tumor
      tissue was analyzed for mutations in 49 oncogenes. We also compared these
      mutations with cytology results. RESULTS: 57.1% of DNA samples from tumor tissue
      were positive for a mutation. In these patients, 87.5% of the bile circulating
      tumor DNA (ctDNA) samples had the same mutation. The concordance rate between
      bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies
      detected in ctDNA were approximately half of what was detected in tumor tissue
      DNA. On the other hand, the sensitivity of the cytological and bile ctDNA
      analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology
      and bile ctDNA analyses was 87.5%. CONCLUSIONS: Mutated tumor DNA could be
      detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa
      because of higher sensitivity and positive predict value compared to cytology
      with ERCP.

PMID- 29580154
TI  - Inhibitory Gi/O-coupled receptors in somatosensory neurons: Potential therapeutic
      targets for novel analgesics.
AB  - Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are
      responsible for sensing mechanical and thermal stimuli, as well as detecting
      tissue damage. These neurons express ion channels that respond to thermal,
      mechanical, or chemical cues, conduct action potentials, and mediate transmitter
      release. These neurons also express a large number of G-protein coupled
      receptors, which are major transducers for extracellular signaling molecules, and
      their activation usually modulates the primary transduction pathways. Receptors
      that couple to phospholipase C via heterotrimeric Gq/11 proteins and those that
      activate adenylate cyclase via Gs are considered excitatory; they positively
      regulate somatosensory transduction and they play roles in inflammatory
      sensitization and pain, and in some cases also in inducing itch. On the other
      hand, receptors that couple to Gi/o proteins, such as opioid or GABAB receptors,
      are generally inhibitory. Their activation counteracts the effect of Gs
      stimulation by inhibiting adenylate cyclase, as well as exerts effects on ion
      channels, usually resulting in decreased excitability. This review will summarize
      knowledge on Gi-coupled receptors in sensory neurons, focusing on their roles in
      ion channel regulation and discuss their potential as targets for analgesic and
      antipruritic medications.

PMID- 29580157
TI  - Spontaneous response to and expressive regulation of mirth elicited by humorous
      cartoons in younger and older adults.
AB  - Many studies have examined the effect of aging on the ability to regulate
      negative emotions but less is known about the way the elderly people control
      their positive affects. Thirty-eight younger and 38 older adults were compared on
      their affective, expressive, physiological, and behavioral spontaneous responses
      to and in expressive regulation of mirth elicited by humorous cartoons. Compared
      to younger adults, older adults were equally amused and aroused but showed lower
      expressivity in their spontaneous reaction. They were similarly successful in
      implementing expressive regulation but they had lower physiological activation
      under amplification condition and more gaze avoidance from the key areas of the
      cartoons under suppression condition. This indicates that in older, amplification
      skills are disjointed from the physiological responses and suppression skills
      seem supplanted by a less costly strategy of attention redeployment. This also
      suggests that older adults' behavior is not driven by a greater preference for
      positive information.

PMID- 29580158
TI  - Quantifying beetle-macrofungal associations in a temperate biodiversity hot spot.
AB  - Beetles (Coleoptera) are often among the most abundant and diverse insects that
      feed on sporocarps of macrofungi, but little is known regarding their relative
      specialism or generalism in most communities. We surveyed >9000 sporocarps in
      montane hardwood forest in the Appalachian Mountains (USA) to characterize
      associations of mycophagous beetles and macrofungi. We used traditional metrics
      and network analyses to quantify relationships between sporocarp traits (mass,
      age, persistence, and toughness) and assemblages of adult beetles, drawing from
      >50 000 beetles collected over two survey years. Strict-sense specificity was
      rare in these associations: most beetle species were found on multiple fungal
      genera, and most fungi hosted multiple beetle species. Sporocarp age and fresh
      mass were positively associated with beetle diversity in fungi with ephemeral
      sporocarps (here including 12 genera of Agaricales and Russulales), but sporocarp
      persistence was not. In Polyporales, beetle diversity was greater in softer
      sporocarps than in tough or woody sporocarps. The increase of beetle diversity in
      aging sporocarps could not be attributed to increases in sporocarp mass or
      sampling point in the growing season, suggesting that age-related changes in
      chemistry or structure may support increasingly diverse beetle communities.
      Interaction networks differed as a function of sporocarp age, revealing that
      community-wide measures of generalism (i.e., network connectance) and evenness
      (i.e., variance in normalized degree) change as sporocarps mature and senesce.
      Beetles observed on Agaricales and Russulales with more persistent sporocarps had
      narrower interaction breadth (i.e., were more host-specific) than those on less
      persistent sporocarps, and beetles on Polyporales with tougher sporocarps had
      narrower interaction breadth than those on soft sporocarps. In addition to
      providing a large-scale evaluation of sporocarp use by adult beetles in this
      temperate biodiversity hot spot, this study shows that characteristics of food
      organisms are associated with specialism and generalism in interactions relevant
      to fungal and forest ecology.

PMID- 29580159
TI  - A systematic review and meta-analysis of the effects of educating parents on the
      benefits and schedules of childhood vaccinations in low and middle-income
      countries.
AB  - Public health benefits of childhood vaccinations risk being derailed by low
      vaccination coverage in low and middle-income countries. One reason for the low
      coverage is poor parental knowledge of the importance of completing vaccination
      schedules. We therefore assessed the effects on childhood vaccination coverage,
      of educating parents and other persons assuming the parental role. We
      prospectively registered the systematic review, published the protocol, and used
      standard Cochrane methods to collect and synthesise the evidence. We found six
      eligible randomised trials with 4248 participants. Three trials assessed health
      facility based education of mothers on the importance of completing vaccination
      schedules; immediately after birth and three months later (one study) or during
      the first vaccination visit (two studies). The other trials assessed community
      based education, including information campaigns on the importance of vaccines
      using audiotaped presentations and leaflet distributions (one study); structured
      group discussions on benefits and costs of childhood vaccination and local action
      plans for improving vaccine uptake (one study); and home-based information
      sessions using graphic cards showing benefits and costs of childhood vaccinations
      and location of vaccination centres (one study). Combining the data shows that
      these interventions lead to substantial improvements in childhood vaccination
      coverage (relative increase 36%, 95% confidence interval 14% to 62%). There was
      no difference between the effects of community-based and facility-based
      education. Therefore, education in communities and health facilities on the
      importance of childhood vaccinations should be integrated into all vaccination
      programmes in low and middle-income countries; accompanied by robust monitoring
      of impacts and use of data for action.

PMID- 29580160
TI  - Significant transcriptome and cytokine changes in hepatitis B vaccine non
      responders revealed by genome-wide comparative analysis.
AB  - Individuals fail to elicit protective antibody after hepatitis B vaccination
      remain at risk for hepatitis B virus infection. Analysis of the transcriptome of
      peripheral blood mononuclear cells (PBMCs) is essential to elucidate the
      characteristics of gene expression in non-responders. In this study, we enrolled
      seven responders who had received three injections and seven non-responders who
      had six injections of hepatitis B vaccine before. All the participants were then
      vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay
      were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine
      and chemokine profiles in non-responders and responders. Differentially expressed
      genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3rd,
      7th, 28th day post the first dose vaccination and 7th day post the second dose
      vaccination indicated a dense network trend. Compared with responders, nine
      coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were
      significantly up-regulated in non-responders at all 5 time points, which could
      probably be the characteristic genes in hepatitis B vaccine non-responsiveness.
      Gene ontology analysis revealed that most of the DEGs were related with immune
      responses. Validation results of these 9 genes using quantitative real-time
      polymerase chain reaction were mostly consistent with the results of microarray.
      Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders
      were significantly higher than non-responders on the 3rd day after the first dose
      and 7th day after the second dose of vaccination, respectively. No significant
      difference was observed in other cytokine and chemokine signatures between the
      two groups. In conclusion, our results revealed characteristic transcriptome and
      cytokine changes in hepatitis B vaccine non-responders after boost immunization.

PMID- 29580161
TI  - Comparison of EpCAMhighCD44+ cancer stem cells with EpCAMhighCD44- tumor cells in
      colon cancer by single-cell sequencing.
AB  - Cancer stem cells (CSCs) are considered to be responsible for tumorigenesis and
      cancer relapse. EpCAMhighCD44+ tumor cells are putative colorectal CSCs that
      express high levels of stem cell genes, while the EpCAMhighCD44- population
      mostly contains differentiated tumor cells (DTCs). This study aims to determine
      whether single CSC (EpCAMhighCD44+) and DTC (EpCAMhighCD44-) can be distinguished
      in terms of somatic copy number alterations (SCNAs). We applied fluorescence
      activated cell sorting to isolate the CD45-EpCAMhighCD44+ and CD45-EpCAMhighCD44-
      populations from two primary colon tumors, on which low-coverage single-cell
      whole-genome sequencing (WGS) was then performed ~0.1x depth. We compared the
      SCNAs of the CSCs and DTCs at single-cell resolution. In total, 47 qualified
      single cells of the two populations underwent WGS. The single-cell SCNA profiles
      showed that there were obvious SCNAs in both the CSCs and DTCs of each patient,
      and each patient had a specific copy number alteration pattern. Hierarchical
      clustering and correlation analysis both showed that the SCNA profiles of CSCs
      and DTCs from the same patient had similar SCNA pattern, while there were
      regional differences in the CSCs and DTCs in certain patient. SCNAs of CSCs in
      the same patient were highly reproducible. Our data suggest that major SCNAs
      occurred at an early stage and were inherited steadily. The similarity of
      ubiquitous SCNAs between the CSCs and DTCs might have arisen from lineage
      differentiation. CSCs from the same patient had reproducible SCNA profiles,
      indicating that gain or loss in certain chromosome is required for colon cancer
      development.

PMID- 29580162
TI  - Updates in pancreatic cancer: Modest gains and hopeful targets.
AB  - Pancreatic cancer is the twelfth most common cancer in the United States,
      representing 3.2% of all new cancer cases. While composing a small percentage of
      cancer diagnoses, pancreatic cancer is amongst the most lethal carcinomas, with
      an overall 5-year survival of 8.2% and incidence rates almost equivocal to death
      rates. By the time of diagnosis, a majority of patients will present with
      advanced stage disease. For patients with resectable disease, the estimated
      overall survival (OS) remains low at 20% as most will develop metastatic disease
      within 5 years. The lethality of this cancer is attributed to several factors
      including delayed presentation, lack of effective screening, and complex tumor
      biology and genetics. Data also suggest that even upon early presentation,
      pancreatic cancer is a systemic disease with micrometastasis present in the early
      stages. Traditional cytotoxic therapies have not been clinically impactful in
      pancreatic cancer, especially in advanced stages, and very little headway has
      been made in the development of new targeted therapies. As such, this review will
      discuss current advances in standard of care treatments and novel drug targets
      being researched.

PMID- 29580163
TI  - From Homer and Hippocrates to modern personalized medicine: is there a role for
      pharmacoepigenomics in the treatment of alcohol addiction?
AB  - From the earliest times to the present, alcohol has evolved as part of life and
      culture. For most adults, moderate alcohol use is harmless, however, it lies at
      one end of a range that moves through alcohol abuse to alcohol addiction. Alcohol
      addiction is a serious and chronic psychiatric disorder that, on top of its heavy
      consequences on health, also brings significant social and economic losses to
      individuals and society at large. Pharmacotherapy of alcohol addiction exists,
      but its effectiveness varies significantly among individuals. Genomic and
      nongenomic factors are significant contributors to interindividual variation in
      the clinical presentation of alcohol problems and the response to a given
      treatment. In addition, emerging evidence suggests pharmacoepigenomics of alcohol
      addiction as a novel promising area for improvement of alcohol addiction
      management.

PMID- 29580164
TI  - Emergence of KRAS-mutation in liver metastases after an anti-EGFR treatment in
      patient with colorectal cancer: Are we aware of the therapeutic impact of
      intratumor heterogeneity?
AB  - Tumors represent a dynamic system where the genomic plasticity permits to adapt
      to the perturbation induced by environmental pressures, supporting the importance
      of longitudinal tumor sampling strategies to deciphering the temporal acquisition
      of driver event that could impact treatment outcome. We describe the case of a
      metastatic colorectal cancer (mCRC) patient, RAS wild-type, who responded to anti
      EGFR therapy and underwent liver surgery, revealing a KRAS mutations in the
      metastatic lesion, not detectable prior to initiation of therapy in the colonic
      biopsy. After liver surgery, the patient received chemotherapy alone, then
      underwent left colectomy and the final pathological report confirmed the KRAS
      wild-type status. We can speculate the existence of two distinct populations of
      KRAS wild-type and mutant CRC cells sharing the same genetic origin. The anti
      EGFR treatment represented a selective pressure which allowed the selection of
      KRAS mutant subclones. The prognostic and /or predictive role of intratumor
      heterogeneity has not been assessed prospectively. Our case report is of clinical
      relevance because patients with mCRC who respond to anti-EGFR antibodies often
      develop resistance within several months of initiating therapy, thus outlining
      the importance to better ascertain the molecular landscape of tumors to design
      better therapeutic strategies.

PMID- 29580165
TI  - Accelerometer and GPS Analysis of Trail Use and Associations With Physical
      Activity.
AB  - BACKGROUND: Concurrent use of accelerometers and global positioning system (GPS)
      data can be used to quantify physical activity (PA) occurring on trails. This
      study examined associations of trail use with PA and sedentary behavior (SB) and
      quantified on trail PA using a combination of accelerometer and GPS data.
      METHODS: Adults (N = 142) wore accelerometer and GPS units for 1-4 days. Trail
      use was defined as a minimum of 2 consecutive minutes occurring on a trail, based
      on GPS data. We examined associations between trail use and PA and SB. On trail
      minutes of light-intensity, moderate-intensity, and vigorous-intensity PA, and SB
      were quantified in 2 ways, using accelerometer counts only and with a combination
      of GPS speed and accelerometer data. RESULTS: Trail use was positively associated
      with total PA, moderate-intensity PA, and light-intensity PA (P < .05). On trail
      vigorous-intensity PA minutes were 346% higher when classified with the
      combination versus accelerometer only. Light-intensity PA, moderate-intensity PA,
      and SB minutes were 15%, 91%, and 85% lower with the combination, respectively.
      CONCLUSIONS: Adult trail users accumulated more PA on trail use days than on
      nontrail use days, indicating the importance of these facilities for supporting
      regular PA. The combination of GPS and accelerometer data for quantifying on
      trail activity may be more accurate than accelerometer data alone and is useful
      for classifying intensity of activities such as bicycling.

PMID- 29580166
TI  - Anaesthetic effects of alfaxalone administered intraperitoneally alone or
      combined with dexmedetomidine and fentanyl in the rat.
AB  - Alfaxalone is a neuroactive steroid used as a general anaesthetic in several
      species including dogs, cats, rabbits and ferrets. It has a wide margin of safety
      and a similar anaesthetic profile to propofol. To increase its aqueous
      solubility, a new formulation with cyclodextrins has been marketed recently. The
      objective of this study was to evaluate the anaesthetic effect of several doses
      of alfaxalone alone, considering differences between sexes, and alfaxalone
      combined with dexmedetomidine and fentanyl in the rat administered by the
      intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three
      studies, were used. Firstly, 25, 35 and 45 mg kg-1 of alfaxalone alone were
      tested. In a second study, alfaxalone (25 mg kg-1, females; 75 mg kg-1, males)
      was combined with dexmedetomidine (0.05 mg kg-1). Finally, alfaxalone (20 mg kg
      1, females; 60 mg kg-1, males) was combined with dexmedetomidine (0.05 mg kg-1)
      and fentanyl (0.1 mg kg-1). Times of onset and duration of anaesthesia, and
      analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone
      alone produced a 2 - to 3-fold longer time of anaesthesia in females, although
      surgical anaesthesia was not achieved in either sex. The addition of
      dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia
      as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone
      produces light anaesthesia in rats, and males required a higher dose. The
      combination with other sedatives or analgesics, such as dexmedetomidine or
      fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially
      suitable for invasive procedures.

PMID- 29580167
TI  - Evaluation of heat stress and heat strain among employees working outdoors in an
      extremely hot environment.
AB  - A heat stress evaluation was conducted among employees engaged in strenuous work
      in an extremely hot outdoor environment. Environmental conditions that contribute
      to heat stress along with various physiological indicators of heat strain were
      monitored on a task-basis for nine employees daily across four workdays.
      Employees performed moderate to heavy tasks in elevated environmental conditions
      for longer periods of time than recommended by various heat stress exposure
      limits. Seven of nine employees showed evidence of excessive heat strain
      according to criteria yet all employees were able to self-regulate task duration
      and intensity to avoid heat-related illness.

PMID- 29580169
TI  - Integration of membrane separation and Fenton processes for sanitary landfill
      leachate treatment.
AB  - The appropriate treatment of sanitary landfill leachate is one of the greatest
      challenges nowadays due to the large volumes of solid waste generated. Thus, the
      aim of this study is to evaluate the performance of different routes involving
      the integration of advanced oxidation processes based on Fenton's reagents (AOP
      Fenton) and microfiltration (MF) and nanofiltration (NF) membrane processes for
      the treatment of landfill leachate. MF module configuration (submerged or
      sidestream) and MF and NF recovery rate were evaluated. The combination of AOP
      Fenton, MF and NF proved to be an effective treatment for landfill leachate. High
      removal efficiencies of chemical oxidation demand (94-96%) and colour (96-99%)
      were obtained. The configuration named route 3, composed of MF of raw landfill
      leachate (MF1), POA-Fenton-MF2 of the MF1 concentrate and NF of both MF1 and MF2
      permeates, showed a higher global water recovery and was responsible for lower
      waste generation. It was considered the best one in terms of environmental,
      technical and economical aspects.

PMID- 29580170
TI  - Comparison of Therapeutic Triiodothyronine Versus Metoprolol in the Treatment of
      Myocardial Infarction in Rats.
AB  - BACKGROUND: Beta blockers are standard therapy for myocardial infarction (MI).
      Preclinical studies have shown efficacy and safety of thyroid hormone (TH)
      treatment of cardiovascular disorders. Since THs interact with the
      sympathoadrenergic system, this study aimed to compare triiodothyronine (T3) and
      metoprolol (Met) in the treatment of rats with MI on pathophysiology and TH
      adrenergic signaling. METHODS: Female Sprague-Dawley rats aged 12 weeks underwent
      left anterior descending coronary artery ligation (MI) or sham surgeries. T3 (5
      MUg/kg/day) or Met (100 mg/kg/day) was given in drinking water immediately after
      surgery for eight weeks. At the terminal of the experiments, the rats were
      subjected to morphological, functional, and molecular examination. RESULTS: T3
      and Met significantly enhanced left ventricular contractility (left ventricular
      fractional shortening 21.37 +/- 2.58% and 21.14 +/- 3.71%, respectively) compared
      to untreated MI (17.88 +/- 1.23%), and decreased the incidence of inducible
      atrial tachyarrhythmia by 87.5% and 62.5%, respectively. Although both treatments
      showed efficacy, T3 but not Met showed statistically significant improvements
      compared to MI in arrhythmia duration, left atrial diameter (T3 vs. MI 4.33 +/-
      0.63 vs. 5.65 +/- 1.32 mm; p < 0.05), fibrosis (6.1 +/- 0.6%, 6.6 +/- 0.6% vs.
      8.2 +/- 0.7%, T3, Met vs. MI, respectively), and aortic vasorelaxation
      responsiveness to acetylcholine (pD2 6.97 +/- 0.22, 6.83 +/- 0.21 vs. 6.66 +/-
      0.22, T3, Met vs. MI, respectively). Quantitative polymerase chain reaction
      showed that T3 and Met attenuated expression of genes associated with
      inflammation and oxidative stress and restored expression of ion channels and
      contractile proteins. CONCLUSION: These results support comparable efficacy of T3
      and Met treatments, suggesting that T3 may provide a therapeutic alternative to
      standard beta-receptor blockade, especially for patients intolerant to treatment
      with beta-blockers after MI.

PMID- 29580171
TI  - MRI for Fetal Developmental Brain Abnormalities: Perspectives From the Pregnant
      Patient.
AB  - Ultrasound is routinely used as a prenatal screening and diagnostic tool but has
      limitations. Some anomalies in the developing fetal brain can be difficult to
      detect, and in utero magnetic resonance imaging (iuMRI) is increasingly used as
      an adjunct to ultrasound. However, understandings of patient perspectives of
      iuMRI technology are still developing. Our qualitative study of 41 mothers who
      experienced iuMRI was embedded in a diagnostic accuracy trial and aimed to inform
      policy recommendations that might stem from the clinical findings. Our analysis
      suggests that iuMRI is seen as useful, offering valuable additional information
      and helping women make decisions about care options at a difficult time. However,
      patients' experiences demonstrated the uncertainty and anxiety associated with
      the prenatal diagnosis (PND) process relating to brain anomalies including the
      challenges of their embodied contributions. Our findings suggest more could be
      done to reduce the impact on pregnant women during an already difficult, anxious
      period.

PMID- 29580168
TI  - Photocrosslinkable Gelatin/Tropoelastin Hydrogel Adhesives for Peripheral Nerve
      Repair.
AB  - Suturing peripheral nerve transections is the predominant therapeutic strategy
      for nerve repair. However, the use of sutures leads to scar tissue formation,
      hinders nerve regeneration, and prevents functional recovery. Fibrin-based
      adhesives have been widely used for nerve reconstruction, but their limited
      adhesive and mechanical strength and inability to promote nerve regeneration
      hamper their utility as a stand-alone intervention. To overcome these challenges,
      we engineered composite hydrogels that are neurosupportive and possess strong
      tissue adhesion. These composites were synthesized by photocrosslinking two
      naturally derived polymers, gelatin-methacryloyl (GelMA) and methacryloyl
      substituted tropoelastin (MeTro). The engineered materials exhibited tunable
      mechanical properties by varying the GelMA/MeTro ratio. In addition, GelMA/MeTro
      hydrogels exhibited 15-fold higher adhesive strength to nerve tissue ex vivo
      compared to fibrin control. Furthermore, the composites were shown to support
      Schwann cell (SC) viability and proliferation, as well as neurite extension and
      glial cell participation in vitro, which are essential cellular components for
      nerve regeneration. Finally, subcutaneously implanted GelMA/MeTro hydrogels
      exhibited slower degradation in vivo compared with pure GelMA, indicating its
      potential to support the growth of slowly regenerating nerves. Thus, GelMA/MeTro
      composites may be used as clinically relevant biomaterials to regenerate nerves
      and reduce the need for microsurgical suturing during nerve reconstruction.

PMID- 29580172
TI  - Paw preferences in the Asian small-clawed otter - using an inexpensive, video
      based protocol to study laterality of rare species in the zoo.
AB  - It is still debated whether limb-use preferences represent a common trait in
      vertebrates, which is based on a shared phylogenetic history. Unravelling the
      evolutionary origin and pattern of paw preferences in vertebrates requires the
      analysis of a larger number of species within an ecologically relevant setting.
      We therefore investigated whether observations in a zoo enable the collection of
      reliable data sets by quantifying paw use in two independent groups of Asian
      small-clawed otters (Amblonyx cinerea). Employing a continuous focal animal
      sampling method, each day one of the ten individuals was video recorded from
      outside of the enclosure during usual activity. We selected four types of
      unimanual behaviour (reaching for food, reaching for non-food, reaching into a
      hole, carrying an object) and quantified paw use for each animal. Our study
      provides first evidences for individual paw preferences in otters, which were in
      line with previously reported forelimb use pattern in carnivoran species.
      Preferences differed between motor acts but for "reaching into a hole" a
      population-level right paw bias was detected. These data support that
      observations in a zoological setting are useful to explore task-dependent paw
      preferences and may facilitate future studies investigating paw preferences under
      experimentally controlled conditions.

PMID- 29580173
TI  - Reinforced Electrospun Polycaprolactone Nanofibers for Tracheal Repair in an In
      Vivo Ovine Model.
AB  - Tracheal stenosis caused by congenital anomalies, tumors, trauma, or intubation
      related damage can cause severe breathing issues, diminishing the quality of
      life, and potentially becoming fatal. Current treatment methods include
      laryngotracheal reconstruction or slide tracheoplasty. Laryngotracheal
      reconstruction utilizes rib cartilage harvested from the patient, requiring a
      second surgical site. Slide tracheoplasty involves a complex surgical procedure
      to splay open the trachea and reconnect both segments to widen the lumen. A clear
      need exists for new and innovative approaches that can be easily adopted by
      surgeons, and to avoid harvesting autologous tissue from the patient. This study
      evaluated the use of an electrospun patch, consisting of randomly layered
      polycaprolactone (PCL) nanofibers enveloping 3D-printed PCL rings, to create a
      mechanically robust, suturable, air-tight, and bioresorbable graft for the
      treatment of tracheal defects. The study design incorporated two distinct uses of
      PCL: electrospun fibers to promote tissue integration, while remaining air-tight
      when wet, and 3D-printed rings to hold the airway open and provide external
      support and protection during the healing process. Electrospun, reinforced
      tracheal patches were evaluated in an ovine model, in which all sheep survived
      for 10 weeks, although an overgrowth of fibrous tissue surrounding the patch was
      observed to significantly narrow the airway. Minimal tissue integration of the
      surrounding tissue and the electrospun fibers suggested the need for further
      improvement. Potential areas for further improvement include a faster degradation
      rate, agents to increase cellular adhesion, and/or an antibacterial coating to
      reduce the initial bacterial load.

PMID- 29580174
TI  - Effect of hydrochlorothiazide on serum uric acid concentration: a genome-wide
      association study.
AB  - AIM: To recognize genetic associations of hydrochlorothiazide-induced change in
      serum uric acid (SUA) concentration. PATIENTS & METHODS: We conducted a genome
      wide association study on hydrochlorothiazide-induced change in SUA in 214
      Finnish men from the GENRES study. Replication analyses were performed in 465
      Finns from the LIFE study. RESULTS: In GENRES, we identified 31 loci associated
      with hydrochlorothiazide-induced change in SUA at p < 5 * 10-5. rs1002976 near
      VEGFC associated with the change in GENRES and in LIFE. rs950569 near BRINP3
      associated with the change in SUA in GENRES and LIFE. The analysis of previously
      reported SNPs and candidate genes provided some proof for PADI4 and ABCC4.
      CONCLUSION: We report genetic markers that may predict the increase in SUA
      concentration during thiazide treatment.

PMID- 29580175
TI  - The Usage of Digital Resources by Swedish Suicide Bereaved in Their Grief Work: A
      Survey Study.
AB  - This study examined Swedish suicide bereaved individuals' use of different
      resources in their grief work and how they value these resources. The material
      consisted of a web-based survey, which was analyzed with quantitative methods.
      The results showed that the psychosocial ill-health was severe among the suicide
      bereaved participants and that a majority used digital resources in their grief
      work. The propensity to engage in online support groups or memorial websites was
      not predicted by the severity of psychosocial consequences following the suicide.
      However, multiple regressions showed that higher online support group activity
      predicted more satisfaction with current psychosocial health, while memorial
      websites seemed to have the opposite effect. This study not only indicates that
      some digital resources, for example, online support groups, may be an effective
      way of coping with grief related to suicide loss, but also suggests that memorial
      websites may increase rumination and in this way cause emotional distress.

PMID- 29580176
TI  - Reliability and Validity of Tethered Swimming Lactate Minimum Test and Their
      Relationship With Performance in Young Swimmers.
AB  - PURPOSE: To test the reliability and validity of tethered swimming lactate
      minimum test in young swimmers. METHODS: Lactate minimum test was performed twice
      to test the reliability (experiment 1; n = 13). In addition, the validity was
      investigated through lactate minimum test relationships with tethered swimming
      lactate threshold and peak force obtained during graded exercise test (experiment
      2; n = 11). Finally, the correlations with mean speeds observed during 200-m
      (s200m) and 30-minute continuous efforts (s30min) were also analyzed (experiment
      3; n = 15). In all experiments, the lactate minimum test began with 3-minute all
      out effort to induce lactatemia, followed by an exhaustive graded exercise test.
      RESULTS: The lactate minimum intensity and mean force during the entire 3-minute
      all-out effort (MF) showed high reliability (coefficient of variation < 8.9% and
      intraclass correlation coefficient > .93). The lactate minimum intensity was not
      different compared with lactate threshold (P = .22), presenting high correlations
      (r = .92) and agreement (95% limits of agreement = +/-7.9 N). The mean force
      during the entire 3-minute all-out effort was similar to peak force obtained
      during graded exercise test (P = .41), presenting significant correlations (r =
      .88) and high indices of agreement (95% limits of agreement = +/-11.3 N). In
      addition, lactate minimum test parameters correlated both with mean speeds
      observed during 200-m (r > .74) and 30-minute continuous efforts (r > .70).
      CONCLUSION: Thus, tethered swimming lactate minimum test can be used for training
      recommendations and to monitor aerobic adaptations in young swimmers.

PMID- 29580177
TI  - Sensor-triggered sampling to determine instantaneous airborne vapor exposure
      concentrations.
AB  - It is difficult to measure transient airborne exposure peaks by means of
      integrated sampling for organic chemical vapors, even with very short-duration
      sampling. Selection of an appropriate time to measure an exposure peak through
      integrated sampling is problematic, and short-duration time-weighted average
      (TWA) values obtained with integrated sampling are not likely to accurately
      determine actual peak concentrations attained when concentrations fluctuate
      rapidly. Laboratory analysis for integrated exposure samples is preferred from a
      certainty standpoint over results derived in the field from a sensor, as a sensor
      user typically must overcome specificity issues and a number of potential
      interfering factors to obtain similarly reliable data. However, sensors are
      currently needed to measure intra-exposure period concentration variations (i.e.,
      exposure peaks). In this article, the digitized signal from a photoionization
      detector (PID) sensor triggered collection of whole-air samples when toluene or
      trichloroethylene vapors attained pre-determined levels in a laboratory
      atmosphere generation system. Analysis by gas chromatography-mass spectrometry of
      whole-air samples (with both 37 and 80% relative humidity) collected using the
      triggering mechanism with rapidly increasing vapor concentrations showed good
      agreement with the triggering set point values. Whole-air samples (80% relative
      humidity) in canisters demonstrated acceptable 17-day storage recoveries, and
      acceptable precision and bias were obtained. The ability to determine exceedance
      of a ceiling or peak exposure standard by laboratory analysis of an
      instantaneously collected sample, and to simultaneously provide a calibration
      point to verify the correct operation of a sensor was demonstrated. This latter
      detail may increase the confidence in reliability of sensor data obtained across
      an entire exposure period.

PMID- 29580178
TI  - Combining NSAM and CPC concentrations to determine airborne nanoparticle count
      median diameter: Application to various laboratory and workplace aerosols.
AB  - Because nanomaterials have been increasingly developed and used in many
      technology and industry sectors over the last 20 years, an increasing number of
      workers is likely to be exposed to airborne nanoparticles. In addition, the
      question of the nanomaterial characteristics that should be assessed in
      epidemiological studies remains open. Thus, assessing occupational exposure to
      airborne nanoparticles will not only rely on mass concentration and chemical
      composition. Rather, key parameters, such as particle size, have to be included
      in measurement strategies. We previously proposed a methodology to estimate the
      Count Median Diameter (CMD) of an aerosol based on the simultaneous size
      integrated measurement of two particle concentrations, lung-deposited surface
      area, and number, thanks to field-portable, commercially available aerosol
      instruments (Nanoparticle Surface Area Monitor/Condensation Particle Counter
      combination). In addition to previous work, this study investigates the case of
      various polydisperse metal oxides, organic oil, and salt particles with CMDs
      ranging from 16-410 nm. Once corrected, the CMDs derived from the NSAM/CPC agree
      within +/-20% with regard to the reference electrical mobility equivalent
      diameter, regardless of aerosol composition, morphology, or geometric standard
      deviation (GSD). Furthermore, the field-applicability of the method was tested
      through 6 sets of experimental data stemming from workplace measurement campaigns
      where different materials were produced and handled (TiO2, SiO2, Ag, Multi-Walled
      Carbon Nanotubes-MWCNT), covering a range of CMDs between 40 and 190 nm. All
      situations considered, the approach based on the combination of a NSAM and a CPC
      leads to a satisfying estimation of particle CMD, within +/-20% compared to
      reference CMD.

PMID- 29580179
TI  - The IARC Perspective on Colorectal Cancer Screening.

PMID- 29580180
TI  - Response to Cuttler et al. re: "Low-Dose Childhood Radiation Effects to the
      Thyroid Follow a Linear Dose-Response Trend and Persist Even 45+ Years After
      Exposure".

PMID- 29580181
TI  - Decellularized Cartilage Directs Chondrogenic Differentiation: Creation of a
      Fracture Callus Mimetic.
AB  - Complications that arise from impaired fracture healing have considerable
      socioeconomic implications. Current research in the field of bone tissue
      engineering predominantly aims to mimic the mature bone tissue microenvironment.
      This approach, however, may produce implants that are intrinsically unresponsive
      to the cues present during the initiation of fracture repair. As such, this study
      describes the development of decellularized xenogeneic hyaline cartilage matrix
      in an attempt to mimic the initial reparative phase of fracture repair. Three
      approaches based on vacuum-assisted osmotic shock (Vac-OS), Triton X-100 (Vac
      STx), and sodium dodecyl sulfate (Vac-SDS) were investigated. The Vac-OS
      methodology reduced DNA content below 50 ng/mg of tissue, while retaining 85% of
      the sulfate glycosaminoglycan content, and as such was selected as the optimal
      methodology for decellularization. The resultant Vac-OS scaffolds (decellularized
      extracellular matrix [dcECM]) were also devoid of the immunogenic alpha-Gal
      epitope. Furthermore, minimal disruption to the structural integrity of the dcECM
      was demonstrated using differential scanning calorimetry and fluorescence
      lifetime imaging microscopy. The biological integrity of the dcECM was confirmed
      by its ability to drive the chondrogenic commitment and differentiation of human
      chondrocytes and periosteum-derived cells, respectively. Furthermore,
      histological examination of dcECM constructs implanted in immunocompetent mice
      revealed a predominantly M2 macrophage-driven regenerative response both at 2 and
      8 weeks postimplantation. These findings contrasted with the implanted native
      costal cartilage that elicited a predominantly M1 macrophage-mediated
      inflammatory response. This study highlights the capacity of dcECM from the Vac
      OS methodology to direct the key biological processes of endochondral
      ossification, thus potentially recapitulating the callus phase of fracture
      repair.

PMID- 29580182
TI  - Perceived importance and difficulty of online activities among visually impaired
      persons in Nigeria.
AB  - This study investigated perceived relevance of and difficulties in access to day
      to-day online activities among visually impaired computer users who used screen
      readers. The 98 participants in the study were grouped into visually impaired
      adults (aged 20-59, n = 60) and visually impaired older adults (aged 60 and over,
      n = 38). Data were collected in structured interview questionnaires with Likert
      scales exploring ratings of perceived importance and difficulty of access to 11
      online platforms of various internet activities. Analyses revealed that the two
      groups did not differ significantly in ratings of perceived importance of four
      major online activities, namely sending or reading email (p = 0.5224), online
      banking (p = 0.2833), online shopping (p = 0.1829), and health information
      seeking (p = 0.1414). The topmost rated activity of priority among both groups
      was sending and reading emails. Findings also show that, apart from sending and
      reading emails, activities rated as important were mostly perceived as difficult
      to access. The implications of the study for inclusive design and strategies
      and/or interventions to encourage uptake of internet use among the visually
      impaired population are discussed.

PMID- 29580183
TI  - 13th International Workshop on Resistance to Thyroid Hormone and Thyroid Hormone
      Action.

PMID- 29580184
TI  - Launching the dialogue: Safety and innovation as partners for success in advanced
      manufacturing.
AB  - Emerging and novel technologies, materials, and information integrated into
      increasingly automated and networked manufacturing processes or into traditional
      manufacturing settings are enhancing the efficiency and productivity of
      manufacturing. Globally, there is a move toward a new era in manufacturing that
      is characterized by: (1) the ability to create and deliver more complex designs
      of products; (2) the creation and use of materials with new properties that meet
      a design need; (3) the employment of new technologies, such as additive and
      digital techniques that improve on conventional manufacturing processes; and (4)
      a compression of the time from initial design concept to the creation of a final
      product. Globally, this movement has many names, but "advanced manufacturing" has
      become the shorthand for this complex integration of material and technology
      elements that enable new ways to manufacture existing products, as well as new
      products emerging from new technologies and new design methods. As the breadth of
      activities associated with advanced manufacturing suggests, there is no single
      advanced manufacturing industry. Instead, aspects of advanced manufacturing can
      be identified across a diverse set of business sectors that use manufacturing
      technologies, ranging from the semiconductors and electronics to the automotive
      and pharmaceutical industries. The breadth and diversity of advanced
      manufacturing may change the occupational and environmental risk profile,
      challenge the basic elements of comprehensive health and safety (material,
      process, worker, environment, product, and general public health and safety), and
      provide an opportunity for development and dissemination of occupational and
      environmental health and safety (OEHS) guidance and best practices. It is unknown
      how much the risk profile of different elements of OEHS will change, thus
      requiring an evolution of health and safety practices. These changes may be
      accomplished most effectively through multi-disciplinary, multi-sector, public
      private dialogue that identifies issues and offers solutions.

PMID- 29580185
TI  - Assessing occupational erionite and respirable crystalline silica exposure among
      outdoor workers in Wyoming, South Dakota, and Montana.
AB  - Erionite is a naturally occurring fibrous mineral found in many parts of the
      world, including the western United States. Inhalational exposure to erionite
      fibers in some localities is associated with health effects similar to those
      caused by asbestos exposure, including malignant mesothelioma. Therefore, there
      is concern regarding occupational exposures in the western United States.
      Currently, there are no standard sampling and analytical methods for airborne
      erionite fibers, as well as no established occupational exposure limits. Due to
      the potential adverse health effects, characterizing and minimizing exposures is
      prudent. Crystalline silica also occurs naturally in areas where erionite is
      found, principally as the mineral quartz. Work activities involving rocks
      containing quartz and soils derived from those rocks can lead to exposure to
      respirable crystalline silica (RCS). The typically dry and dusty environment of
      the western United States can increase the likelihood of exposures to aerosolized
      rocks and soils, but inhalation exposure is also possible in more humid
      conditions. In this case study, we describe several outdoor occupational
      environments with potential exposures to erionite and RCS. We describe our method
      for evaluating those exposures and demonstrate: (1) the occurrence of
      occupational exposures to airborne erionite and RCS, (2) that the chemical make
      up of the erionite mineral can be determined, and (3) that effective dust control
      practices are needed to reduce employee exposures to these minerals.

PMID- 29580186
TI  - Chronic Discrimination and Sleep Problems in Late Life: Religious Involvement as
      Buffer.
AB  - The association between chronic discrimination and sleep problems is important to
      examine in older adults because sleep is highly reactive to stress and impaired
      sleep has diverse adverse health effects. The association between chronic
      discrimination and sleep problems may, however, be confounded by a number of time
      stable influences, and this association may also vary by religious involvement.
      In three waves (2006, 2010, and 2014) of the Health and Retirement Study ( N =
      7,130), the overall association between chronic discrimination and sleep problems
      is negated in econometric models that control for all time-stable sources of
      confounding. Religious involvement does not modify this association for men, but
      a significant association is found among women who do not attend religious
      services. These analyses suggest that the association between chronic
      discrimination and sleep quality in late life is substantially inflated due to
      unobserved time-stable confounders, although women who do not attend religious
      services may be at risk.

PMID- 29580187
TI  - Grandparenting and Self-Rated Health Among Older Korean Women.
AB  - An increasing number of older Korean women have played an important role in
      taking care of their grandchildren to help their adult children. This study
      investigates the effects of grandparenting on older women' health in South Korea.
      Using the Korean Longitudinal Study of Aging ( N = 3,092), we estimated ordinal
      logistic regression models with lagged dependent variable to examine whether and
      how grandparenting type and transition and grandparenting intensity are
      associated with older women's self-rated health. Results show that grandmothers
      who provide long-term nonresidential grandparenting have better self-rated health
      than grandmothers who are not engaged in grandparenting. Grandmothers caring for
      grandchildren in skipped-generation households or multigenerational households do
      not suffer from a deficit in health. Grandparenting intensity is not associated
      with grandmothers' health. Our findings suggest that the implications of
      grandparenting for older women's health may differ in different social and
      cultural contexts.

PMID- 29580188
TI  - Ovarian cancer-derived extracellular vesicles affect normal human fibroblast
      behavior.
AB  - It has become clear that non-tumor cells in the microenvironment, especially
      fibroblasts, actively participate in tumor progression. Fibroblasts conditioned
      by tumor cells become "activated" and, as such, are identified as CAFs (cancer
      associated fibroblasts). These CAFs remodel the tumor stroma to make it more
      favourable for cancer progression. The aim of this work was to verify whether EVs
      (extracellular vesicles - whose role as mediators of information between tumor
      and stromal cells is well known) released from human ovarian cancer cells were
      able to activate fibroblasts. EVs isolated from SKOV3 (more aggressive) and CABA
      I (less aggressive) cells were administered to fibroblasts. The consequent
      activation was supported by morphological and molecular changes in treated
      fibroblasts; XTT assays, zymographies, wound healing tests and invasion assays
      also highlighted higher proliferation, motility, invasiveness and enzyme
      expression. The secretome of these "activated" fibroblasts was, in turn, able to
      modulate the responses (proliferation, motility and invasion) of fibroblasts, and
      of tumor and endothelial cells. These findings support the idea that ovarian
      cancer cells can modulate fibroblast behaviour through the release of EVs,
      activating them to a CAFs-like state; the latter are able, in turn, to stimulate
      the surrounding cells. EVs from SKOV3 rather than from CABA I seem to be more
      efficient in some processes.

PMID- 29580189
TI  - Occupational exposure monitoring data collection, storage, and use among state
      based and private workers' compensation insurers.
AB  - Despite substantial financial and personnel resources being devoted to
      occupational exposure monitoring (OEM) by employers, workers' compensation
      insurers, and other organizations, the United States (U.S.) lacks comprehensive
      occupational exposure databases to use for research and surveillance activities.
      OEM data are necessary for determining the levels of workers' exposures;
      compliance with regulations; developing control measures; establishing worker
      exposure profiles; and improving preventive and responsive exposure surveillance
      and policy efforts. Workers' compensation insurers as a group may have particular
      potential for understanding exposures in various industries, especially among
      small employers. This is the first study to determine how selected state-based
      and private workers' compensation insurers collect, store, and use OEM data
      related specifically to air and noise sampling.  Of 50 insurers contacted to
      participate in this study, 28 completed an online survey. All of the responding
      private and the majority of state-based insurers offered industrial hygiene (IH)
      services to policyholders and employed 1 to 3 certified industrial hygienists on
      average. Many, but not all, insurers used standardized forms for data collection,
      but the data were not commonly stored in centralized databases. Data were most
      often used to provide recommendations for improvement to policyholders. Although
      not representative of all insurers, the survey was completed by insurers that
      cover a substantial number of employers and workers. The 20 participating state
      based insurers on average provided 48% of the workers' compensation insurance
      benefits in their respective states or provinces. These results provide insight
      into potential next steps for improving the access to and usability of existing
      data as well as ways researchers can help organizations improve data collection
      strategies. This effort represents an opportunity for collaboration among
      insurers, researchers, and others that can help insurers and employers while
      advancing the exposure assessment field in the U.S.

PMID- 29580190
TI  - Sami yoik, Sami history, Sami health: a narrative review.
AB  - Music as a possible health-promoting agent has attained increasing academic and
      scientific interest over the last decades. Nonetheless, possible connections
      between indigenous singing traditions and health beyond traditional ceremonial
      healing practices are still under-researched worldwide. The Sami, the indigenous
      people living in Northern Fennoscandia, have a distinct ancient vocal music
      tradition called "yoik" practiced from immemorial times. The Sami share a history
      of assimilation with many indigenous people. During this period of nearly 400
      years, yoik alongside other cultural markers was under hard pressure and even
      banned at times. Compared to other indigenous people in the Arctic, Sami public
      health shows few significant unfavourable differences to the majority population.
      The potential role of yoik as a protective health and resilience factor within
      the Sami culture is the topic of this review. We suggest a two stage model for
      the health promoting effects of yoik through i) emotion regulation and stress
      relief on the level of the individual, and ii) as a socio-cultural resilience
      factors within the Sami population. This review is to be understood as theory
      building review article striving for a scholarly review of the literature.

PMID- 29580192
TI  - Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms.
AB  - While the use of vinegar to fi ght against infections and other crucial
      conditions dates back to Hippocrates, recent research has found that vinegar
      consumption has a positive effect on biomarkers for diabetes, cancer, and heart
      diseases. Different types of vinegar have been used in the world during different
      time periods. Vinegar is produced by a fermentation process. Foods with a high
      content of carbohydrates are a good source of vinegar. Review of the results of
      different studies performed on vinegar components reveals that the daily use of
      these components has a healthy impact on the physiological and chemical structure
      of the human body. During the era of Hippocrates, people used vinegar as a
      medicine to treat wounds, which means that vinegar is one of the ancient foods
      used as folk medicine. The purpose of the current review paper is to provide a
      detailed summary of the outcome of previous studies emphasizing the role of
      vinegar in treatment of different diseases both in acute and chronic conditions,
      its in vivo mechanism and the active role of different bacteria.

PMID- 29580193
TI  - Releasability of asbestos fibers from weathered roof cement.
AB  - Chrysotile asbestos fibers were added to roofing products, including roof cement,
      for several decades. The fibers were described as "encapsulated" and therefore
      incapable of being released, an assertion that is disproved by the study reported
      herein. Three test panels of roof cement from the original container were exposed
      to ambient weathering in 2015 and 2016. Two panels were then sampled using the
      ASTM D5755 microvacuum method. Sampling revealed a light brown sub-layer under
      the dark brown surface layer, both of which crumbled and became friable during
      sampling. Analysis of the microvacuum samples with transmission electron
      microscopy showed that the material on the 2 panels contained 4,432,000 and
      3,320,000 asbestos structures per cm2 with nearly all of the structures
      consisting of fibers less than 5 um long. Energy dispersive spectrometry
      determined that none of the fibers reported were coated with asphalt. The
      presence of free fibers was confirmed by direct examination of the surfaces of
      the panels and of dust released from handling the panels via scanning electron
      microscopy. This study confirmed the releasability of uncoated asbestos fibers
      from dried roof cement that was indicated in 2 previous studies published in 2007
      and 2010. These results suggest that the finding of the Fifth Circuit Court in
      1997 that uncoated airborne asbestos fibers cannot be released from roof cement,
      and therefore do not present a potential exposure by inhalation, was erroneous in
      retrospect. The exemption of roof cement from regulation under the Occupational
      Safety and Health Administration Construction Industry Standard for asbestos by
      the Court should not be relied on by employers of workers who remove weathered
      asbestos-containing roof cement, and precautions should be taken against exposure
      to airborne asbestos fibers during this work.

PMID- 29580194
TI  - Post-licensure safety surveillance of zoster vaccine live (Zostavax(r)) in the
      United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.
AB  - BACKGROUND: Herpes zoster (HZ), or shingles, is caused by reactivation of
      varicella-zoster virus in latently infected individuals. Live-attenuated HZ
      vaccine (zoster vaccine live, ZVL) is approved in the United States for persons
      aged >=50 years and recommended by the CDC for persons >=60 years. METHODS: We
      analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the
      Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to
      monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31,
      2015. We conducted descriptive analysis, clinical reviews of reports with
      selected pre-specified conditions, and empirical Bayesian data mining. RESULTS:
      VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were
      classified as non-serious. Of reports where age was documented (n = 18,817), 83%
      were in persons aged >=60 years. Reporting rates of AEs were 106 and 4.4 per
      100,000 ZVL doses distributed for all reports and serious reports, respectively.
      When ZVL was administered alone among persons aged >=50 years, injection site
      erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the
      most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%),
      and rash (16%) were the most commonly reported symptoms among serious reports.
      Six reports included laboratory evidence of vaccine-strain varicella-zoster virus
      (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and
      local reaction with vesicles. In our review of reports of death with sufficient
      information to determine cause (n = 46, median age 75 years), the most common
      causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical
      Bayesian data mining did not detect new or unexpected safety signals.
      CONCLUSIONS: Findings from our safety review of ZVL are consistent with those
      from pre-licensure clinical trials and other post-licensure assessments.
      Transient injection-site reactions, HZ, and rashes were most frequently reported
      to VAERS following ZVL. Overall, our results are reassuring regarding the safety
      of ZVL.

PMID- 29580195
TI  - Sex Differences in the Association Between Gaming and Serious Violence Among
      Predominantly African American Youth.
AB  - Video gaming, a remarkably popular hobby in the United States, has been
      consistently identified as a correlate of aggressive behavior, and this
      association is not limited to violent video gaming. Prior studies of sex
      differences in the association between video gaming and aggression have not
      controlled for other well-known violence correlates (e.g., substance use,
      community violence exposure, violence attitudes) or focused primarily on high
      risk youth. In this study, we used data from an emergency department in Flint,
      Michigan ( N = 409, 59.9% female, 93.4% African American) to identify sex
      differences in the association between video gaming and serious peer violence.
      Youth aged 14 to 20 years were recruited from October 2011 to March 2015, and
      self-administered computerized surveys including measures of demographics,
      violence perpetration, gaming frequency, substance use, community violence
      exposure, and violence attitudes. The primary outcome was an indicator of any
      serious violence perpetration (e.g., choking, burning, weapon violence) in the
      past 2 months. Using logistic regression, we estimated the association between
      gaming and serious violence perpetration, and how it varied by sex, while
      controlling for demographics, substance use, community violence exposure, and
      violence attitudes. Approximately 36.6% of males and 27.3% of females reported
      past 2-month serious violence. On adjusted analysis, hours spent gaming was
      associated with violence among females (odds ratio [OR] = 1.40, 95% confidence
      interval [CI] = [1.16, 1.78]), but not males (OR = 1.03, 95% CI = [0.89, 1.19]);
      in the model including both males and females, the interaction between hours
      gaming and sex was significant ( p < .01). Our findings suggest video gaming is a
      stronger marker of severe violence perpetration in females than males among at
      risk youth. Violence interventions among females may be improved by including
      content related to video gaming and identifying other prosocial activities for
      youth as an alternative to video gaming. Additional research is required to
      clarify the causal process underlying the identified associations, and to
      determine what aspects of video gaming are risk-enhancing.

PMID- 29580196
TI  - Family Violence: An Insight Into Perspectives and Practices of Australian Health
      Practitioners.
AB  - Family violence is threatening behavior carried out by a person to coerce or
      control another member of the family or causes the family member to be fearful.
      Health practitioners are well placed to play a pivotal role in identifying and
      responding to family violence; however, their perceived capacity to respond to
      patients experiencing family violence is not well understood. We aim to explore
      Australian health practitioners' current perspectives, practices, and perceived
      barriers in working with family violence, including perceived confidence in
      responding effectively to cases of family violence encountered during their work
      with patients. A total of 1,707 health practitioners primarily practicing in the
      wider Melbourne region were identified, and 114 health practitioners participated
      in the study between March 2016 and August 2016 by completing an investigator
      developed questionnaire. Descriptive, qualitative, and thematic analyses were
      performed. The majority of participants recognized family violence to be a health
      issue and that family violence would impact the mental health of afflicted
      persons. Despite this, only a fifth of participants felt they were very confident
      in screening, supporting, and referring patients with family violence
      experiences. Perceived barriers to inquire about family violence included time
      constraints and greater importance placed on screening for other health issues.
      Health practitioners reported that additional training on screening, supporting,
      and referring patients would be beneficial. Australian health practitioners need
      to be upskilled. Recently, in Australia, state-relevant toolkits have been
      developed to provide succinct information about responding to initial patient
      presentations of family violence, how to inquire about family violence, and how
      to handle disclosures (and nondisclosures) by patients. Further resources could
      be developed to aid health practitioners in providing assistance to their
      patients as indicated. These initiatives would be a step toward addressing the
      concerns with regard to the lack of training and could possibly optimize outcomes
      for patients experiencing family violence.

PMID- 29580197
TI  - Identifying Youth at Risk for Commercial Sexual Exploitation Within Child
      Advocacy Centers: A Statewide Pilot Study.
AB  - Commercial sexual exploitation of children (CSEC) is a social problem in the
      United States that has recently received growing attention from policy makers,
      advocates, and researchers. Despite increasing awareness of this issue,
      information on the prevalence, demographic profile, and psychosocial needs of
      victims of CSEC is scarce. To better understand the scope of CSEC and to examine
      the feasibility of screening for CSEC in Child Advocacy Centers (CACs), a pilot
      study was initiated through Arkansas Building Effective Services for Trauma
      (ARBEST) to identify youth who may be at risk for commercial sexual exploitation.
      Data for this pilot study were collected from all of the state's CACs ( n = 14)
      over a 6-month period. Family advocates completed a screening questionnaire
      adapted from Greenbaum, Dodd, and McCracken with 918 youth aged 12 to 18 years
      old treated at CACs. Almost 20% of youth were identified as being at high risk
      for experiencing CSEC. Furthermore, youth classified as high-risk for commercial
      sexual exploitation reported significantly more avoidance symptoms on the UCLA
      (University of California at Los Angeles) PTSD (Posttraumatic Stress Disorder)
      Reaction Index than youth classified as low-risk. The results suggest that a
      significant portion of youth treated at CACs in Arkansas are at high risk for
      experiencing commercial sexual exploitation, which may be associated with a
      particular pattern of trauma symptoms. These findings also lend support for the
      feasibility and utilization of a screening questionnaire as part of routine care
      in CACs to potentially identify youth at risk for CSEC.

PMID- 29580198
TI  - Pharmacogenetics of oral antidiabetic therapy.
AB  - Type 2 diabetes prevalence is still on the rise worldwide. Antidiabetic drugs are
      widely prescribed to patients with Type 2 diabetes. Most patients start with
      metformin which is mostly well tolerated. However, a high percentage of patients
      fail to achieve glycemic control. The effectiveness of metformin as well as most
      other antidiabetic drugs depends among other factors on interindividual genetic
      differences that are up to now ignored in the treatment of Type 2 diabetes.
      Interestingly, many genes influencing the effectiveness of antidiabetic drugs are
      Type 2 diabetes risk genes making matters worse. Here, we shed light on these
      interindividual genetic differences.

PMID- 29580199
TI  - Screening of Pig (Sus scrofa) Bactericidal Permeability-Increasing Protein (BPI)
      Gene as Marker for Disease Resistance.
AB  - Salmonella infection can cause septicemia, acute or chronic enteritis and wasting
      in weaned pigs, but may occur in other age groups. The bactericidal/permeability
      increasing protein (BPI) gene plays an important role in the natural defense of
      the host and is found to be associated with resistance/susceptibility to
      Salmonella infection and identified as a candidate gene for disease resistance
      breeding in pig. This study was conducted to screen the resistance and/or
      susceptibility of pigs to Salmonella infection, to determine the genotype and
      evaluate presence of resistant allele of the BPI gene in population of pigs, and
      to establish genetic data for pig breeders for the improvement of Philippine pig
      industry. In this study, 389 blood samples from different pig breeds were
      collected from pig breeder farms in the Philippines. Genomic DNA was extracted
      from these samples and genotyping was done by PCR-RFLP analysis using AvaII
      restriction enzyme. Out of 389 pigs, the genotypic frequency showed that 98.4,
      1.3, and 0.3% pigs are resistant (GG), heterozygous type (AG), and susceptible
      (AA), respectively. The application of BPI gene as marker for disease resistance
      will provide information to the pig industry to implement strategies for the
      identification of Salmonella infection-resistant pigs.

PMID- 29580200
TI  - Evaluating the effect of training along with fit testing on earmuff users in a
      Chinese textile factory.
AB  - A hearing protection fit testing was conducted on workers (n = 189) in a textile
      factory in southern China. The 3M E-A-Rfit Dual-Ear Validation System was used to
      measure the personal attenuation rating (PAR) on an over-the-head style earmuff
      at the work site. In addition, PARs were obtained several times throughout the
      same work shift to capture different fits on 39 workers. Follow-up visits were
      conducted in approximate 6-month or 12-month intervals to repeat the fit testing.
      Both the immediate and residual effects of training on the field attenuation of
      hearing protection devices obtained by workers, and the effects of training
      toward improving the attenuation and protection of earmuffs after a period of
      daily use, were observed. A questionnaire survey was used to assess the awareness
      of hearing health and motivation toward the use of earmuffs in a high temperature
      environment. The results showed that there were wide variations in PARs among the
      workers tested. The one-on-one training together with fit testing improved PAR
      and helped to reduce the negative impact caused by use of protective hair covers.
      Since earmuffs are often used for long periods of time (>1 year), repeating fit
      tests could be helpful in order to verify the attenuation received throughout
      their useful life.

PMID- 29580201
TI  - Combining six genome scan methods to detect candidate genes to salinity in the
      Mediterranean striped red mullet (Mullus surmuletus).
AB  - BACKGROUND: Adaptive genomics may help predicting how a species will respond to
      future environmental changes. Genomic signatures of local adaptation in marine
      organisms are often driven by environmental selective agents impacting the
      physiology of organisms. With one of the highest salinity level, the
      Mediterranean Sea provides an excellent model to investigate adaptive genomic
      divergence underlying salinity adaptation. In the present study, we combined six
      genome scan methods to detect potential genomic signal of selection in the
      striped red mullet (Mullus surmuletus) populations distributed across a wide
      salinity gradient. We then blasted these outlier sequences on published fish
      genomic resources in order to identify relevant potential candidate genes for
      salinity adaptation in this species. RESULTS: Altogether, the six genome scan
      methods found 173 outliers out of 1153 SNPs. Using a blast approach, we
      discovered four candidate SNPs belonging to three genes potentially implicated in
      adaptation of M. surmuletus to salinity. The allele frequency at one of these
      SNPs significantly increases with salinity independently from the effect of
      longitude. The gene associated to this SNP, SOCS2, encodes for an inhibitor of
      cytokine and has previously been shown to be expressed under osmotic pressure in
      other marine organisms. Additionally, our results showed that genome scan methods
      not correcting for spatial structure can still be an efficient strategy to detect
      potential footprints of selection, when the spatial and environmental variation
      are confounded, and then, correcting for spatial structure in a second step
      represents a conservative method. CONCLUSION: The present outcomes bring
      evidences of potential genomic footprint of selection, which suggest an adaptive
      response of M. surmuletus to salinity conditions in the Mediterranean Sea.
      Additional genomic data such as sequencing of a full-genome and transcriptome
      analyses of gene expression would provide new insights regarding the possibility
      that some striped red mullet populations are locally adapted to their saline
      environment.

PMID- 29580203
TI  - Sample size determination for mediation analysis of longitudinal data.
AB  - BACKGROUND: Sample size planning for longitudinal data is crucial when designing
      mediation studies because sufficient statistical power is not only required in
      grant applications and peer-reviewed publications, but is essential to reliable
      research results. However, sample size determination is not straightforward for
      mediation analysis of longitudinal design. METHODS: To facilitate planning the
      sample size for longitudinal mediation studies with a multilevel mediation model,
      this article provides the sample size required to achieve 80% power by
      simulations under various sizes of the mediation effect, within-subject
      correlations and numbers of repeated measures. The sample size calculation is
      based on three commonly used mediation tests: Sobel's method, distribution of
      product method and the bootstrap method. RESULTS: Among the three methods of
      testing the mediation effects, Sobel's method required the largest sample size to
      achieve 80% power. Bootstrapping and the distribution of the product method
      performed similarly and were more powerful than Sobel's method, as reflected by
      the relatively smaller sample sizes. For all three methods, the sample size
      required to achieve 80% power depended on the value of the ICC (i.e., within
      subject correlation). A larger value of ICC typically required a larger sample
      size to achieve 80% power. Simulation results also illustrated the advantage of
      the longitudinal study design. The sample size tables for most encountered
      scenarios in practice have also been published for convenient use. CONCLUSIONS:
      Extensive simulations study showed that the distribution of the product method
      and bootstrapping method have superior performance to the Sobel's method, but the
      product method was recommended to use in practice in terms of less computation
      time load compared to the bootstrapping method. A R package has been developed
      for the product method of sample size determination in mediation longitudinal
      study design.

PMID- 29580202
TI  - Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a
      potential role of macrophages.
AB  - BACKGROUND: We sought to identify the carcinoembryonic antigen (CEA) as a marker
      of radioresistance in rectal cancer. METHODS: From July 1997 to January 2008, 104
      patients with stage II or III rectal cancer who were treated with post-operative
      radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged
      from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the
      actuarial rates of overall survival (OS), distant metastasis (DM), and local
      recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed
      with Cox regression models. We used THP-1 monocyte cell lines for macrophage
      differentiation (M0, M1 or M2). The RNA extracted from the macrophages was
      analyzed via a genomic method in the core laboratory. The radiosensitivities of
      CEA-rich LS1034 cells were compared between cells with and without the
      conditioned media from CEA-stimulated macrophages. RESULTS: Preoperative CEA
      levels >=10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p =
      0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA
      levels < 10 ng/mL and >=10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively.
      The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding
      rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA
      elicited a dose-response relationship with M2 differentiation. In the CEA
      stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including
      MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of
      GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells
      elicited an increase in the numbers of LS180, SW620, and LS1034 cells after
      irradiation. CEA caused the M2 differentiation of the macrophages. CONCLUSION:
      Pretreatment CEA levels >=10 ng/mL are a significant risk factor for OS, DM, and
      LR following PORT for rectal cancer. CEA causes radioresistance in the presence
      of M2 macrophages. More comprehensive examinations prior to surgery and intensive
      adjuvant therapy are suggested for patients with CEA levels >=10 ng/mL. Further
      studies of these mechanisms are needed.

PMID- 29580204
TI  - Anti-EGFR targeted therapy delivered before versus during radiotherapy in
      locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence
      platform-based analysis.
AB  - BACKGROUND: Little is known about the prognostic difference of anti-EGFR therapy,
      cetuximab (CTX) or nimotuzumab (NTZ), concurrently with induction chemotherapy
      (IC, investigational arm) or RT (control arm) for patients with locoregionally
      advanced nasopharyngeal carcinoma (LA-NPC). We conducted this retrospective study
      to address this. METHODS: We identified 296 patients with newly diagnosed LA-NPC
      at Sun Yat-Sen University Cancer Center between January 2012 and May 2015.
      Patients were treated by IC with CCRT or RT and CTX/NTZ was delivered during IC
      or radiotherapy. Survival outcomes and toxicities between different arms were
      compared. RESULTS: In total, there were 149 patients in the investigational arm
      and 147 in control arm. The 3-year disease-free survival, overall survival,
      distant metastasis-free survival and locoregional relapse-free survival rates for
      investigational arm vs. control arm were 84.3% vs. 74.3% (P = 0.027), 94.0% vs.
      92.1% (P = 0.673), 88.0% vs. 81.8% (P = 0.147) and 93.3% vs. 88.0% (P = 0.093).
      Multivariate analysis revealed patients in the control arm achieved significantly
      worse disease-free survival (HR, 1.497; 95% CI, 1.016-2.206; P = 0.026) compared
      with those in the investigational arm; however, no significant difference was
      identified for other endpoints. Patients in the investigational arm experienced
      more grade 3-4 skin reaction (15.4% vs. 2.0%, P <  0.001) and mucositis (10.1%
      vs. 3.4%, P = 0.022) during induction phase, but less skin reaction (5.4% vs.
      25.9%, P <  0.001) and mucositis (24.8% vs. 36.7%, P = 0.026) during RT.
      CONCLUSIONS: Our findings suggested that CTX/NTZ concurrently with IC may be a
      more effective and promising strategy for patients with LA-NPC receiving
      intensity-modulated radiotherapy.

PMID- 29580207
TI  - The effect of Kenya's free maternal health care policy on the utilization of
      health facility delivery services and maternal and neonatal mortality in public
      health facilities.
AB  - BACKGROUND: Kenya abolished delivery fees in all public health facilities through
      a presidential directive effective on June 1, 2013 with an aim of promoting
      health facility delivery service utilization and reducing pregnancy-related
      mortality in the country. This paper aims to provide a brief overview of this
      policy's effect on health facility delivery service utilization and maternal
      mortality ratio and neonatal mortality rate in Kenyan public health facilities.
      METHODS: A time series analysis was conducted on health facility delivery
      services utilization, maternal and neonatal mortality 2 years before and after
      the policy intervention in 77 health facilities across 14 counties in Kenya.
      RESULTS: A statistically significant increase in the number of facility-based
      deliveries was identified with no significant changes in the ratio of maternal
      mortality and the rate of neonatal mortality. CONCLUSION: The findings suggest
      that cost is a deterrent to health facility delivery service utilization in Kenya
      and thus free delivery services are an important strategy to promote utilization
      of health facility delivery services; however, there is a need to simultaneously
      address other factors that contribute to pregnancy-related and neonatal deaths.

PMID- 29580205
TI  - Primordial origin and diversification of plasmids in Lyme disease agent bacteria.
AB  - BACKGROUND: With approximately one-third of their genomes consisting of linear
      and circular plasmids, the Lyme disease agent cluster of species has the most
      complex genomes among known bacteria. We report here a comparative analysis of
      plasmids in eleven Borreliella (also known as Borrelia burgdorferi sensu lato)
      species. RESULTS: We sequenced the complete genomes of two B. afzelii, two B.
      garinii, and individual B. spielmanii, B. bissettiae, B. valaisiana and B.
      finlandensis isolates. These individual isolates carry between seven and sixteen
      plasmids, and together harbor 99 plasmids. We report here a comparative analysis
      of these plasmids, along with 70 additional Borreliella plasmids available in the
      public sequence databases. We identify only one new putative plasmid
      compatibility type (the 30th) among these 169 plasmid sequences, suggesting that
      all or nearly all such types have now been discovered. We find that the linear
      plasmids in the non-B. burgdorferi species have undergone the same kinds of
      apparently random, chaotic rearrangements mediated by non-homologous
      recombination that we previously discovered in B. burgdorferi. These
      rearrangements occurred independently in the different species lineages, and
      they, along with an expanded chromosomal phylogeny reported here, allow the
      identification of several whole plasmid transfer events among these species.
      Phylogenetic analyses of the plasmid partition genes show that a majority of the
      plasmid compatibility types arose early, most likely before separation of the
      Lyme agent Borreliella and relapsing fever Borrelia clades, and this, with
      occasional cross species plasmid transfers, has resulted in few if any species
      specific or geographic region-specific Borreliella plasmid types. CONCLUSIONS:
      The primordial origin and persistent maintenance of the Borreliella plasmid types
      support their functional indispensability as well as evolutionary roles in
      facilitating genome diversity. The improved resolution of Borreliella plasmid
      phylogeny based on conserved partition-gene clusters will lead to better
      determination of gene orthology which is essential for prediction of biological
      function, and it will provide a basis for inferring detailed evolutionary
      mechanisms of Borreliella genomic variability including homologous gene and
      plasmid exchanges as well as non-homologous rearrangements.

PMID- 29580206
TI  - Correlates of evolutionary rates in the murine sperm proteome.
AB  - BACKGROUND: Protein-coding genes expressed in sperm evolve at different rates. To
      gain deeper insight into the factors underlying this heterogeneity we examined
      the relative importance of a diverse set of previously described rate correlates
      in determining the evolution of murine sperm proteins. RESULTS: Using partial
      rank correlations we detected several major rate indicators: Phyletic gene age,
      numbers of protein-protein interactions, and survival essentiality emerged as
      particularly important rate correlates in murine sperm proteins. Tissue
      specificity, numbers of paralogs, and untranslated region lengths also correlate
      significantly with sperm genes' evolutionary rates, albeit to a lesser extent.
      Multifunctionality, coding sequence or average intron lengths, and mean
      expression level have insignificant or virtually no independent effects on
      evolutionary rates in murine sperm genes. Gene ontology enrichment analyses of
      three equally sized murine sperm protein groups classified based on their
      evolutionary rates indicate strongest sperm-specific functional specialization in
      the most quickly evolving gene class. CONCLUSIONS: We propose a model according
      to which slowly evolving murine sperm proteins tend to be constrained by factors
      such as survival essentiality, network connectivity, and/or broad expression. In
      contrast, evolutionary change may arise especially in less constrained sperm
      proteins, which might, moreover, be prone to specialize to reproduction-related
      functions. Our results should be taken into account in future studies on rate
      variations of reproductive genes.

PMID- 29580208
TI  - Screening for inhibitors of mutacin synthesis in Streptococcus mutans using
      fluorescent reporter strains.
AB  - BACKGROUND: Within the polymicrobial dental plaque biofilm, bacteria kill
      competitors by excreting mixtures of bacteriocins, resulting in improved fitness
      and survival. Inhibiting their bacteriocin synthesis might therefore be a useful
      strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly
      acidogenic inhabitant of dental plaque, as a model and searched for natural
      products that reduced mutacin synthesis. To this end we fused the promoter of
      mutacin VI to the GFP+ gene and integrated the construct into the genome of S.
      mutans UA159 by single homologous recombination. RESULTS: The resulting reporter
      strain 423p - gfp + was used to screen 297 secondary metabolites from different
      sources, mainly myxobacteria and fungi, for their ability to reduce the
      fluorescence of the fully induced reporter strain by > 50% while growth was
      almost unaffected (> 90% of control). Seven compounds with different chemical
      structures and different modes of action were identified. Erinacine C was
      subsequently validated and shown to inhibit transcription of all three mutacins
      of S. mutans. The areas of the inhibition zones of the sensor strains S.
      sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to
      controls in the presence of erinacine C, demonstrating that the amount of active
      mutacins in the culture supernatants of S. mutans was reduced. Erinacines are
      cyathane diterpenes that were extracted from cultures of the edible mushroom
      Hericium erinaceus. They have anti-inflammatory, antimicrobial and
      neuroprotective effects. For erinacine C, a new biological activity was found
      here. CONCLUSIONS: We demonstrate the successful development of a whole-cell
      fluorescent reporter for the screening of natural compounds and report that
      erinacine C suppresses mutacin synthesis in S. mutans without affecting cell
      viability.

PMID- 29580209
TI  - Physical activity and fitness are associated with verbal memory, quality of life
      and depression among nursing home residents: preliminary data of a randomized
      controlled trial.
AB  - BACKGROUND: Few studies have simultaneously examined changes in physical,
      cognitive and emotional performance throughout the aging process. METHODS:
      Baseline data from an ongoing experimental randomized study were analyzed.
      Physical activity, handgrip, the Senior Fitness Test, Trail Making Test A, Rey
      Auditory-Verbal Learning Test, Quality of Life-Alzheimer's Disease Scale (QoL-AD)
      and the Goldberg Depression Scale were used to assess study participants.
      Logistic regression models were applied. TRIAL REGISTRATION: ACTRN12616001044415
      (04/08/2016). RESULTS: The study enrolled 114 participants with a mean age of
      84.9 (standard deviation 6.9) years from ten different nursing homes. After
      adjusting for age, gender and education level, upper limb muscle strength was
      found to be associated with Rey Auditory-Verbal Learning Test [EXP(B): 1.16, 95%
      confidence interval (CI): 1.04-1.30] and QoL-AD [EXP(B): 1.18, 95% CI: 1.06
      1.31]. Similarly, the number of steps taken per day was negatively associated
      with the risk of depression according to the Goldberg Depression Scale [EXP(B):
      1.14, 95% CI: 1.000-1.003]. Additional analyses suggest that the factors
      associated with these variables are different according to the need for using an
      assistive device for walking. In those participants who used it, upper limb
      muscle strength remained associated with Rey Auditory-Verbal Learning Test
      [EXP(B): 1.21, 95% CI: 1.01-1.44] and QoL-AD tests [EXP(B): 1.19, 95% CI: 1.02
      1.40]. In those individuals who did not need an assistive device for walking,
      lower limb muscle strength was associated with Rey Auditory-Verbal Learning Test
      [EXP(B): 1.35, 95% CI: 1.07-1.69], time spent in light physical activity was
      associated with QoL-AD test [EXP(B): 1.13, 95% CI: 1.00-1.02], and the number of
      steps walked per day was negatively associated with the risk of depression
      according to the Goldberg Depression Scale [EXP(B): 1.27, 95% CI: 1.000-1.004].
      CONCLUSIONS: Muscle strength and physical activity are factors positively
      associated with a better performance on the Rey Auditory-Verbal Learning Test,
      QoL-AD and Goldberg Depression Scale in older adults with mild to moderate
      cognitive impairment living in nursing homes. These associations appeared to
      differ according to the use of an assistive device for walking. Our findings
      support the need for the implementation of interventions directed to increase the
      strength and physical activity of individuals living in nursing homes to promote
      physical, cognitive and emotional benefits. TRIAL REGISTRATION:
      ACTRN12616001044415 (04/08/2016).

PMID- 29580210
TI  - Defense against territorial intrusion is associated with DNA methylation changes
      in the honey bee brain.
AB  - BACKGROUND: Aggression is influenced by individual variation in temperament as
      well as behavioral plasticity in response to adversity. DNA methylation is stably
      maintained over time, but also reversible in response to specific environmental
      conditions, and may thus be a neuromolecular regulator of both of these
      processes. A previous study reported DNA methylation differences between
      aggressive Africanized and gentle European honey bees. We investigated whether
      threat-induced aggression altered DNA methylation profiles in the honey bee brain
      in response to a behavioral stimulus (aggression-provoking intruder bee or inert
      control). We sampled five minutes and two hours after stimulus exposure to
      examine the effect of time on epigenetic profiles of aggression. RESULTS: There
      were DNA methylation differences between aggressive and control bees for
      individual cytosine-guanine dinucleotides (CpGs) across the genome. Eighteen
      individual CpG sites showed significant difference between aggressive and control
      bees 120 min post stimulus. For clusters of CpGs, we report four genomic regions
      differentially methylated between aggressive and control bees at the 5-min time
      point, and 50 regions differentially methylated at the120-minute time point
      following intruder exposure. Differential methylation occurred at genes involved
      in neural plasticity, chromatin remodeling and hormone signaling. Additionally,
      there was a significant overlap of differential methylation with previously
      published epigenetic differences that distinguish aggressive Africanized and
      gentle European honey bees, suggesting an evolutionarily conserved use of brain
      DNA methylation in the regulation of aggression. Lastly, we identified
      individually statistically suggestive CpGs that as a group were significantly
      associated with differentially expressed genes underlying aggressive behavior and
      also co-localize with binding sites of transcription factors involved in
      neuroplasticity or neurodevelopment. CONCLUSIONS: There were DNA methylation
      differences in the brain associated with response to an intruder. These
      differences increased in number a few hours after the initial exposure and
      overlap with previously reported aggression-associated genes and
      neurobiologically relevant transcription factor binding sites. Many DNA
      methylation differences that occurred in association with the expression of
      aggression in real time also exist between Africanized bees and European bees,
      suggesting an evolutionarily conserved role for epigenetic regulation in
      aggressive behavior.

PMID- 29580211
TI  - New insight into the mechanism underlying the silk gland biological process by
      knocking out fibroin heavy chain in the silkworm.
AB  - BACKGROUND: Exploring whether and how mutation of silk protein contributes to
      subsequent re-allocation of nitrogen, and impacts on the timing of silk gland
      degradation, is important to understand silk gland biology. Rapid development and
      wide application of genome editing approach in the silkworm provide us an
      opportunity to address these issues. RESULTS: Using CRISPR/Cas9 system, we
      successfully performed genome editing of Bmfib-H. The loss-of-function mutations
      caused naked pupa and thin cocoon mutant phenotypes. Compared with the wild type,
      the posterior silk gland of mutant showed obviously degraded into fragments in
      advance of programmed cell death of silk gland cells. Comparative transcriptomic
      analyses of silk gland at the fourth day of the fifth instar larval
      stage(L5D4)identified 1456 differential expressed genes (DEGs) between posterior
      silk gland (PSG) and mid silk gland (MSG) and 1388 DEGs between the mutant and
      the wild type. Hierarchical clustering of all the DEGs indicated a remarkable
      down-regulated and an up-regulated gene clade in the mutant silk glands,
      respectively. Down-regulated genes were overrepresented in the pathways involved
      in cancer, DNA replication and cell proliferation. Intriguingly, up-regulated
      DEGs are significantly enriched in the proteasome. By further comparison on the
      transcriptome of MSG and PSG between the wild type and the mutant, we
      consistently observed that up-regulated DEGs in the mutant PSG were enriched in
      protein degrading activity and proteasome. Meantime, we observed a series of up
      regulated genes involved in autophagy. Since these protein degradation processes
      would be normally occur after the spinning time, the results suggesting that
      these progresses were activated remarkably ahead of schedule in the mutant.
      CONCLUSIONS: Accumulation of abnormal fib-H protein might arouse the activation
      of proteasomes as well as autophagy process, to promote the rapid degradation of
      such abnormal proteins and the silk gland cells. Our study therefore proposes a
      subsequent process of protein and partial cellular degradation caused by mutation
      of silk protein, which might be helpful for understanding its impact of the silk
      gland biological process, and further exploration the re-allocation of nitrogen
      in the silkworm.

PMID- 29580212
TI  - Frequency of HPV in oral cavity squamous cell carcinoma.
AB  - BACKGROUND: The prevalence of high-risk human papillomavirus (HPV) DNA in cases
      of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study
      is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort
      of patients with oral cavity SCC. METHODS: Biopsy and resected frozen and
      formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from
      101 patients who were recruited at two Brazilian centres. Stringent measures with
      respect to case selection and prevention of sample contamination were adopted to
      ensure reliability of the data. Nested PCR using MY09/MY11 and GP5+/GP6+ as well
      as PGMY09/11 L1 consensus primers were performed to investigate the presence of
      HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing.
      Shapiro-Wilk and Student t test were used to evaluate data normality and to
      compare the means, respectively. Qualitative variables were analysed by logistic
      regression. RESULTS: Our results demonstrate that the frequency of high-risk HPV
      types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases
      were HPV16. In addition, our results do not show a significant association
      between the tumour clinical features and the risk factors (tobacco, alcohol and
      HPV) for oral cavity SCC. CONCLUSION: In the current study, we observed an
      overlapping pattern of risk factors that are related to tumour development. This,
      along with a low frequency of high-risk HPV DNA, supports the findings that HPV
      is not involved in the genesis of oral cavity SCC in Brazilian population.

PMID- 29580213
TI  - Feasibility and acceptability of expressive writing with postpartum women: a
      randomised controlled trial.
AB  - BACKGROUND: Pregnancy, birth and adjusting to a new baby is a potentially
      stressful time that can negatively affect women's mental and physical health.
      Expressive writing, where people write about a stressful event for at least 15
      min on three consecutive days, has been associated with improved health in some
      groups but it is not clear whether it is feasible and acceptable for use with
      postpartum women. This study therefore examined the feasibility and acceptability
      of expressive writing for postpartum women as part of a randomised controlled
      trial (RCT). METHODS: The Health After Birth Trial (HABiT) was an RCT evaluating
      expressive writing for postpartum women which included measures of feasibility
      and acceptability. At 6 to 12 weeks after birth 854 women were randomised to
      expressive writing, a control writing task or normal care, and outcome measures
      of health were measured at baseline, one month later and six months later.
      Feasibility was measured by recruitment, attrition, and adherence to the
      intervention. Quantitative and qualitative measures of acceptability of the
      materials and the task were completed six months after the intervention. RESULTS:
      Recruitment was low (10.7% of those invited to participate) and the recruited
      sample was from a restricted sociodemographic range. Attrition was high,
      increased as the study progressed (35.8% at baseline, 57.5% at one month, and
      68.1% at six months) and was higher in the writing groups than in the normal care
      group. Women complied with instructions to write expressively or not, but
      adherence to the instruction to write for 15 min per day for three days was low
      (Expressive writing: 29.3%; Control writing: 23.5%). Acceptability measures
      showed that women who wrote expressively rated the materials/task both more
      positively and more negatively than those in the control writing group, and
      qualitative comments revealed that women enjoyed the writing and/or found it
      helpful even when it was upsetting. CONCLUSIONS: The feasibility of offering
      expressive writing as a universal self-help intervention to all postpartum women
      6 to 12 weeks after birth in the HABiT trial was low, but the expressive writing
      intervention was acceptable to the majority of women who completed it. TRIAL
      REGISTRATION: ISRCTN58399513, 10/09/2013.

PMID- 29580214
TI  - Priming effect of root-applied silicon on the enhancement of induced resistance
      to the root-knot nematode Meloidogyne graminicola in rice.
AB  - BACKGROUND: Silicon (Si) can confer plant resistance to both abiotic and biotic
      stress. In the present study, the priming effect of Si on rice (Oryza sativa cv
      Nipponbare) against the root-knot nematode Meloidogyne graminicola and its
      histochemical and molecular impact on plant defense mechanisms were evaluated.
      RESULTS: Si amendment significantly reduced nematodes in rice roots and delayed
      their development, while no obvious negative effect on giant cells was observed.
      Increased resistance in rice was correlated with higher transcript levels of
      defense-related genes (OsERF1, OsEIN2 and OsACS1) in the ethylene (ET) pathway.
      Si amendment significantly reduced nematode numbers in rice plants with enhanced
      ET signaling but had no effect in plants deficient in ET signaling, indicating
      that the priming effects of Si were dependent on the ET pathway. A higher
      deposition of callose and accumulation of phenolic compounds were observed in
      rice roots after nematode attack in Si-amended plants than in the controls.
      CONCLUSION: These findings indicate that the priming effect may partially depend
      on the production of phenolic compounds and hydrogen peroxide. Further research
      is required to model the ethylene signal transduction pathway that occurs in the
      Si-plant-nematode interaction system and gain a better understanding of Si
      induced defense in rice.

PMID- 29580215
TI  - Nomograms predict long-term survival for patients with periampullary
      adenocarcinoma after pancreatoduodenectomy.
AB  - BACKGROUND: The prognosis of patients with periampullary adenocarcinoma after
      pancreatoduodenectomy is diverse and not yet clearly illustrated. The aim of this
      study was to develop a nomogram to predict individual risk of overall survival
      (OS) and progression-free survival (PFS) in patients with periampullary
      adenocarcinoma after pancreatoduodenectomy. METHODS: A total of 205 patients with
      periampullary adenocarcinoma after pancreatoduodenectomy were retrospectively
      included. OS and PFS were evaluated by the Kaplan-Meier method. Two nomograms for
      predicting OS and PFS were established, and the predictive accuracy was measured
      by the concordance index (Cindex) and calibration plots. RESULTS: Lymph node
      ratio (LNR), carbohydrate antigen 19-9 (CA19-9) and anatomical location were
      incorporated into the nomogram for OS prediction and LNR, CA19-9; anatomical
      location and tumor differentiation were incorporated into the nomogram for PFS
      prediction. All calibration plots for the probability of OS and PFS fit well. The
      Cindexes of the nomograms for OS and PFS prediction were 0.678 and 0.68,
      respectively. The OS and PFS survival times were stratified significantly using
      the nomogram-predicted survival probabilities. CONCLUSIONS: The present nomograms
      for OS and PFS prediction can provide valuable information for tailored decision
      making for patients with periampullary adenocarcinoma after
      pancreatoduodenectomy.

PMID- 29580216
TI  - An evaluation of functional mental capacity in forensic mental health practice:
      the Dundrum capacity ladders validation study.
AB  - BACKGROUND: Because of the potential gravity of finding a person incompetent,
      assessment of mental capacity is challenging for clinicians. We aimed to test
      validity of a new structured professional judgement tool designed to assess
      functional mental capacity in three domains - finances, welfare and healthcare.
      METHODS: Fifty-five male forensic psychiatric patients with Schizophrenia were
      interviewed using the Dundrum Capacity Ladders - a new semi-structured interview,
      and scores were assigned on a stratified scoring system, measuring ability to
      understand, reason, appreciate the personal importance of the decision at hand
      and communicate a decision. Data were also gathered pertaining to level of
      therapeutic security at the time of interview, diagnosis, neurocognitive function
      and a validated measure of real world function. RESULTS: The results show that
      internal consistency and inter-rater reliability were high for all items. There
      were correlations between higher scores of functional mental capacity,
      neurocognitive function and measures of real world function in this population.
      Correlations were in the range 0.358 to 0.693, effect sizes that were moderate to
      high. CONCLUSIONS: The DUNDRUM Capacity Ladders appear to be a valid measure of
      functional mental capacity in this population. Further prospective studies of
      functional mental capacity as a measure of recovery are now required.

PMID- 29580218
TI  - Education and employment status of adults with autism spectrum disorders in
      Germany - a cross-sectional-survey.
AB  - BACKGROUND: Adults with autism spectrum disorders (ASD) experience challenges in
      participating in the labour market and struggle to achieve and maintain
      appropriate professional positions, possibly due to impairments of communication
      and social interaction. Studies have shown high rates of unemployment as well as
      evidence of inadequate employment. As knowledge on the participation in the
      German labour market is scarce, the aim of our study was to examine employment
      status, type of occupation and inadequate employment in a sample of clinically
      mostly late-diagnosed and most likely not intellectually disabled adults with ASD
      in Germany. METHODS: We conducted a cross-sectional-survey in clinically mostly
      late-diagnosed adults with ASD. Employment status, type of occupation, and the
      level of formal education and training were examined through a postal
      questionnaire. Inadequate employment regarding participants' current and longest
      practised occupation was assessed by transforming participants' information into
      skill levels of the "Classification of Occupations 2010" of the German Federal
      Employment Agency, and comparing these with participants' level of formal
      education and training. RESULTS: The response rate was 43.2% (N = 185 of N = 428
      potential participants). 94.6% were first-time diagnosed when being 18 years of
      age or older. 56.8% held a general university entrance-level qualification and
      24.9% had obtained a Masters' or diploma degree as their highest vocational
      qualification. 94.1% had been employed at some time. Of these, 68.4% reported
      being currently employed, 13.5% being currently unemployed and 17.0% being
      retired for health reasons. Regarding the longest-practised and the current
      occupation, the highest proportion of participants was found in the occupational
      area "health and social sector, teaching and education" (22.4% and 23.3%,
      respectively). With respect to inadequate employment, 22.1% were found to be
      overeducated in relation to their longest-practised occupation and 31.3% in
      relation to their current occupation. This is significantly higher than the
      percentage of overeducation in the general population. CONCLUSIONS: Despite
      largely high formal qualifications, the clinically mostly late-diagnosed adults
      with ASD represented in our sample are disadvantaged regarding their
      participation in the German labour market, especially with respect to rates of
      unemployment, early retirement and overeducation. Employment support programs
      should be developed to improve employment outcomes.

PMID- 29580217
TI  - Foreign peptide triggers boost in pneumococcal metabolism and growth.
AB  - BACKGROUND: Nonencapsulated Streptococcus pneumoniae bacteria are successful
      colonizers of the human nasopharynx and often possess genes aliB-like ORF 1 and 2
      in place of capsule genes. AliB-like ORF 2 binds peptide FPPQSV, found in
      Prevotella species, resulting in enhanced colonization. How this response is
      mediated is so far unknown. RESULTS: Here we show that the peptide increases
      expression of genes involved in release of host carbohydrates, carbohydrate
      uptake and carbohydrate metabolism. In particular, the peptide increased
      expression of 1,5-anhydro-D-fructose reductase, a metabolic enzyme of an
      alternative starch and glycogen degrading pathway found in many organisms, in
      both transcriptomic and proteomic data. The peptide enhanced pneumococcal growth
      giving a competitive advantage to a strain with aliB-like ORF 2, over its mutant
      lacking the gene. Possession of aliB-like ORF 2 did not affect release of
      inflammatory cytokine CXCL8 from epithelial cells in culture and the
      nonencapsulated wild type strain was not able to establish disease or
      inflammation in an infant rat model of meningitis. CONCLUSIONS: We propose that
      AliB-like ORF 2 confers an advantage in colonization by enhancing carbohydrate
      metabolism resulting in a boost in growth. This may explain the widespread
      presence of aliB-like ORF 2 in the nonencapsulated pneumococcal population in the
      human nasopharynx.

PMID- 29580219
TI  - A Sequel to Sanger: amplicon sequencing that scales.
AB  - BACKGROUND: Although high-throughput sequencers (HTS) have largely displaced
      their Sanger counterparts, the short read lengths and high error rates of most
      platforms constrain their utility for amplicon sequencing. The present study
      tests the capacity of single molecule, real-time (SMRT) sequencing implemented on
      the SEQUEL platform to overcome these limitations, employing 658 bp amplicons of
      the mitochondrial cytochrome c oxidase I gene as a model system. RESULTS: By
      examining templates from more than 5000 species and 20,000 specimens, the
      performance of SMRT sequencing was tested with amplicons showing wide variation
      in GC composition and varied sequence attributes. SMRT and Sanger sequences were
      very similar, but SMRT sequencing provided more complete coverage, especially for
      amplicons with homopolymer tracts. Because it can characterize amplicon pools
      from 10,000 DNA extracts in a single run, the SEQUEL can reduce greatly reduce
      sequencing costs in comparison to first (Sanger) and second generation platforms
      (Illumina, Ion). CONCLUSIONS: SMRT analysis generates high-fidelity sequences
      from amplicons with varying GC content and is resilient to homopolymer tracts.
      Analytical costs are low, substantially less than those for first or second
      generation sequencers. When implemented on the SEQUEL platform, SMRT analysis
      enables massive amplicon characterization because each instrument can recover
      sequences from more than 5 million DNA extracts a year.

PMID- 29580220
TI  - Pragmatic RAndomised controlled trial of a trauma-focused guided self-help
      Programme versus InDividual trauma-focused cognitive Behavioural therapy for post
      traumatic stress disorder (RAPID): trial protocol.
AB  - BACKGROUND: There is good evidence that trauma-focused therapies for Post
      Traumatic Stress Disorder are effective. However, they are not always feasible to
      deliver due a shortage of trained therapists and demands on the patient. An
      online trauma-focused Guided Self-Help (GSH) programme which could overcome these
      barriers has shown promise in a pilot study. This study will be the first to
      evaluate GSH against standard face-to-face therapy to assess its suitability for
      use in the NHS. METHODS: The study is a large-scale multi-centre pragmatic
      randomised controlled non-inferiority trial, with assessors masked to treatment
      allocation. One hundred and ninety-two participants will be randomly allocated to
      receive either face-to-face trauma-focused cognitive behaviour therapy (TFCBT) or
      trauma-focused online guided self-help (GSH). The primary outcome will be the
      severity of symptoms of PTSD over the previous week as measured by the Clinician
      Administered PTSD Scale for DSM5 (CAPS-5) at 16 weeks post-randomisation.
      Secondary outcome measures include PTSD symptoms over the previous month as
      measured by the CAPS-5 at 52 weeks plus the Impact of Event Scale - revised (IES
      R), Work and Social Adjustment Scale (WSAS), Patient Health Questionnaire-9 (PHQ
      9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Test (AUDIT-O),
      Multidimensional Scale for Perceived Social Support (MSPSS), short Post-Traumatic
      Cognitions Inventory (PTCI), Insomnia Severity Index (ISI) and General Self
      Efficacy Scale (GSES) measured at 16 and 52 weeks post-randomisation. Changes in
      health-related quality of life will be measured by the EQ-5D and the level of
      healthcare resource utilisation for health economic analysis will be determined
      by an amended version of the Client Socio-Demographic and Service Receipt
      Inventory European Version. The Client Satisfaction Questionnaire (CSQ) will be
      collected at 16 weeks post-randomisation to evaluate treatment satisfaction.
      DISCUSSION: This study will be the first to compare online GSH with usual face-to
      face therapy for PTSD. The strengths are that it will test a rigorously developed
      intervention in a real world setting to inform NHS commissioning. The potential
      challenges of delivering such a pragmatic study may include participant
      recruitment, retention and adherence, therapist retention, and fidelity of
      intervention delivery. TRIAL REGISTRATION: ISRCTN13697710 registered on
      20/12/2016.

PMID- 29580221
TI  - Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic
      defects and deformation of nuclei in cancer cells.
AB  - BACKGROUND: Nucleocytoplasmic transport is a tightly regulated process carried
      out by specific transport machinery, the defects of which may lead to a number of
      diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the
      karyopherin alpha nuclear importer family, is expressed at a high level during
      embryogenesis, reduced to very low or absent levels in most adult tissues but re
      expressed in cancer cells. METHODS: We used siRNA-based knock-down of KPNA7 in
      cancer cell lines, followed by functional assays (proliferation and cell cycle)
      and immunofluorescent stainings to determine the role of KPNA7 in regulation of
      cancer cell growth, proper mitosis and nuclear morphology. RESULTS: In the
      present study, we show that the silencing of KPNA7 results in a dramatic
      reduction in pancreatic and breast cancer cell growth, irrespective of the
      endogenous KPNA7 expression level. This growth inhibition is accompanied by a
      decrease in the fraction of S-phase cells as well as aberrant number of
      centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7
      depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina
      proteins, and drastic alterations in nuclear morphology with lobulated and
      elongated nuclei. CONCLUSIONS: Taken together, our data provide new important
      evidence on the contribution of KPNA7 to the regulation of cancer cell growth and
      the maintenance of nuclear envelope environment, and thus deepens our
      understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

PMID- 29580222
TI  - Drug-related deaths in Scotland 1979-2013: evidence of a vulnerable cohort of
      young men living in deprived areas.
AB  - BACKGROUND: Even after accounting for deprivation, mortality rates are higher in
      Scotland relative to the rest of Western Europe. Higher mortality from alcohol-
      and drug-related deaths (DRDs), violence and suicide (particularly in young
      adults) contribute to this 'excess' mortality. Age-period and cohort effects help
      explain the trends in alcohol-related deaths and suicide, respectively. This
      study investigated whether age, period or cohort effects might explain recent
      trends in DRDs in Scotland and relate to exposure to the changing political
      context from the 1980s. METHODS: We analysed data on DRDs from 1979 to 2013 by
      sex and deprivation using shaded contour plots and intrinsic estimator regression
      modelling to identify and quantify relative age, period and cohort effects.
      RESULTS: The peak age for DRDs fell around 1990, especially for males as rates
      increased for those aged 18 to 45 years. There was evidence of a cohort effect,
      especially among males living in the most deprived areas; those born between 1960
      and 1980 had an increased risk of DRD, highest for those born 1970 to 1975. The
      cohort effect started around a decade earlier in the most deprived areas compared
      to the rest of the population. CONCLUSION: Age-standardised rates for DRDs among
      young adults rose during the 1990s in Scotland due to an increased risk of DRD
      for the cohort born between 1960 and 1980, especially for males living in the
      most deprived areas. This cohort effect is consistent with the hypothesis that
      exposure to the changing social, economic and political contexts of the 1980s
      created a delayed negative health impact.

PMID- 29580223
TI  - Association between braced curve behavior by pubertal growth peak and bracing
      effectiveness in female idiopathic scoliosis: a longitudinal cohort study.
AB  - BACKGROUND: Pre-pubertal idiopathic scoliosis (IS) is associated with high risk
      of bracing ineffectiveness. Integrated multidimensional maturity assessments are
      useful but complex to predict the high-risk occurrence of curve progression. This
      study is designed to provide a simple screening method for brace effectiveness by
      determining whether or not the braced curve behavior at growth spurt, being
      defined as variations in Cobb angle velocity (AV) at peak height velocity (PHV),
      can be a new factor predictive of brace outcome prescribed before PHV. METHODS:
      This is a retrospective study of a series of 35 IS girls with simplified skeletal
      maturity score no more than 3 at initiation of bracing treatment and followed up
      through the growth spurt until brace weaning or surgery. Serial Cobb angle and
      maturity indicators involving height velocity, Risser sign, triradiate cartilage,
      simplified skeletal maturity score and distal radius and ulna classification were
      assessed and patients were stratified into either a positive or negative category
      based on a positive or negative value of AV at PHV. Comparisons were made between
      the positive and negative AV groups, as well as the failed and successful bracing
      groups, using independent sample T test and crosstab analysis. Logistic
      regression analysis was used to identify the predictive factors of failed brace
      treatment. RESULTS: Brace treatment prescribed before PHV was found to have an
      overall failure rate of 57.1% and a surgical rate of 45.7%. Negative AV at PHV
      accounting for 54.3% of the recruited patients were associated with lower brace
      failure rate (36.8% vs. 81.2%, p = 0.016) and surgical rate (21.1% vs. 75.0%, p =
      0.002). Patients in the failed bracing group showed higher ratio of thoracic
      curve (80.0% vs. 26.7%,p = 0.002) and higher AV at growth peak (2.3 +/- 9.1 vs. 
      6.5 +/- 11.4 degrees /yrs., p = 0.016). The logistic regression analysis revealed
      that positive AV at PHV (OR = 9.268, 95% CI = 1.279-67.137, p = 0.028) and
      thoracic curve type (OR = 13.391, 95% CI = 2.006-89.412, p = 0.007) were strong
      predictive factors of ineffective brace treatment initiated before PHV.
      CONCLUSIONS: Sustained curve correction following bracing despite early onset and
      rapid pubertal growth was strongly predictive of effective brace control of
      scoliosis.

PMID- 29580225
TI  - Psychotropic medication use among patients with celiac disease.
AB  - BACKGROUND: Celiac disease is a multi-system disorder with manifestations that
      may result in psychiatric disorders. We assessed the prevalence of medication use
      to treat psychiatric disorders in celiac disease patients. METHODS: We conducted
      a cross-sectional study of patients undergoing esophagogastroduodenoscopy over 9
      years at a celiac disease referral center. We compared the prevalence of
      psychotropic medication use among celiac disease patients (n = 1293) to a control
      group (n = 1401) with abdominal pain or reflux. RESULTS: Among all patients the
      mean age was 48.4 years, most were female (69.5%), and 22.7% used any
      psychotropic medication. There was no difference between overall psychotropic
      medication use among celiac disease patients and controls (23.9% vs 21.8%, OR
      1.16; 95% CI 0.96-1.39, p = 0.12). However, those with celiac disease were more
      likely to use antidepressants on univariate (16.4% vs 13.4%, p = 0.03) and
      multivariate analysis (OR 1.28; 95% CI 1.03-1.59; p = 0.03). Use of psychotropic
      medications was not associated with disease duration or mode of presentation of
      celiac disease. CONCLUSIONS: Celiac disease patients use psychotropic medications
      at similar rates as those with other gastrointestinal diseases, though subgroup
      analysis suggests they may use more antidepressants. Future studies should
      investigate whether celiac disease is associated with mood disorders that are not
      treated with medications.

PMID- 29580224
TI  - Intraspecific comparative genomics of isolates of the Norway spruce pathogen
      (Heterobasidion parviporum) and identification of its potential virulence
      factors.
AB  - BACKGROUND: Heterobasidion parviporum is an economically most important fungal
      forest pathogen in northern Europe, causing root and butt rot disease of Norway
      spruce (Picea abies (L.) Karst.). The mechanisms underlying the pathogenesis and
      virulence of this species remain elusive. No reference genome to facilitate
      functional analysis is available for this species. RESULTS: To better understand
      the virulence factor at both phenotypic and genomic level, we characterized 15 H.
      parviporum isolates originating from different locations across Finland for
      virulence, vegetative growth, sporulation and saprotrophic wood decay. Wood decay
      capability and latitude of fungal origins exerted interactive effects on their
      virulence and appeared important for H. parviporum virulence. We sequenced the
      most virulent isolate, the first full genome sequences of H. parviporum as a
      reference genome, and re-sequenced the remaining 14 H. parviporum isolates.
      Genome-wide alignments and intrinsic polymorphism analysis showed that these
      isolates exhibited overall high genomic similarity with an average of at least
      96% nucleotide identity when compared to the reference, yet had remarkable intra
      specific level of polymorphism with a bias for CpG to TpG mutations. Reads
      mapping coverage analysis enabled the classification of all predicted genes into
      five groups and uncovered two genomic regions exclusively present in the
      reference with putative contribution to its higher virulence. Genes enriched for
      copy number variations (deletions and duplications) and nucleotide polymorphism
      were involved in oxidation-reduction processes and encoding domains relevant to
      transcription factors. Some secreted protein coding genes based on the genome
      wide selection pressure, or the presence of variants were proposed as potential
      virulence candidates. CONCLUSION: Our study reported on the first reference
      genome sequence for this Norway spruce pathogen (H. parviporum). Comparative
      genomics analysis gave insight into the overall genomic variation among this
      fungal species and also facilitated the identification of several secreted
      protein coding genes as putative virulence factors for the further functional
      analysis. We also analyzed and identified phenotypic traits potentially linked to
      its virulence.

PMID- 29580226
TI  - Prevalence of alcohol consumption and alcohol use disorders among outdoor
      drinkers in public open places in Nigeria.
AB  - BACKGROUND: There is a rapid shift in the social context of drinking, with a
      large proportion of regular drinkers favouring outdoor-open space drinking, such
      as motor-parks, by the road sides, the majority of which are unlicensed premises
      for drinking. METHOD: This study determined the prevalence and determinants of
      harmful or hazardous alcohol use and possible dependence, defined as a "likely
      alcohol use disorder" (AUD) in a community sample of 1119 patrons of open space
      drinking places in Ibadan, Nigeria, using the AUDIT. Scores of 8 and above
      signified a likely AUD. The associations between a likely AUD and demographic
      characteristics were sought using Chi square statistics and binary regression
      analysis was used to determine the effects of multiple confounding variables on a
      likely AUD using the SPSS version 20.0 software. RESULTS: Of the entire
      population, the prevalence of likely AUD was 39.5%, and 44.4% out of the drinking
      population Multivariate analysis showed that Islamic religion was a negative
      predictor for likely AUD, OR = 0.13, 95% CI (0.06-0.26), while rural residence,
      OR = 1.84, 95% CI (1.34-2.53) and cigarette smoking OR = 1.81, 95% CI (1.37-2.40)
      were predictive of likely AUD. CONCLUSION: Outdoor-open space drinkers are likely
      to have AUD compared with the general population. Open space drinking has a huge
      public health implication because of the associated health risks and injuries.

PMID- 29580227
TI  - First case report of M1 macrophage polarization in an untreated symptomatic
      patient with toxoplasmosis.
AB  - BACKGROUND: In immunocompetent patients, acute toxoplasmosis is usually
      asymptomatic. We identified M1 macrophages in a case of symptomatic acute
      Toxoplasma gondii infection that resolved without treatment. M1 macrophages have
      been demonstrated in animal models of toxoplasmosis, but not in humans. CASE
      PRESENTATION: A 63-year-old woman presented with laterocervical and axillary
      bilateral lymphadenopathy. Her anamnesis defined an episode of high fever and
      prolonged asthenia 4 months previously, which suggested an infectious disease.
      Following laboratory, radiological, and pathological analyses, she was diagnosed
      with toxoplasmosis. Immunohistochemical analyses were performed on lymph node
      sections. More than 50% of the macrophages in the lymph node microgranulomas were
      M1 macrophages, defined by CD68+/p-Stat1+ staining, and the presence of T helper
      1 lymphocytes indicated an immune response known to induce M1 macrophage
      polarization. Activated endothelial cells were found only in inflamed areas. No
      therapy was administered before or after diagnosis, and the lymphadenopathy
      resolved after a follow-up of 5 months. CONCLUSIONS: This is the first report to
      demonstrate the presence of M1 macrophages in human toxoplasmosis. Our findings
      contribute to the understanding of the pathogenesis of toxoplasmosis, and
      encourage further studies on the role of macrophage polarization in human
      toxoplasmosis.

PMID- 29580228
TI  - Intra- and interobserver reliability of glenoid fracture classifications by
      Ideberg, Euler and AO.
AB  - BACKGROUND: Representing 3%-5% of shoulder girdle injuries scapula fractures are
      rare. Furthermore, approximately 1% of scapula fractures are
      intraarticularfractures of the glenoid fossa. Because of uncertain fracture
      morphology and limited experience, the treatment of glenoid fossa fractures is
      difficult. The glenoid fracture classification by Ideberg (1984) and Euler (1996)
      is still commonly used in literature. In 2013 a new glenoid fracture
      classification was introduced by the AO. The purpose of this study was to examine
      the new AO classification in clinical practice in comparison with the
      classifications by Ideberg and Euler. METHODS: In total CT images of 84 patients
      with glenoid fossa fractures from 2005 to 2018 were included. Parasagittal,
      paracoronary and axial reconstructions were examined according to the
      classifications of Ideberg, Euler and the AO by 3 investigators (orthopedic
      surgeon, radiologist, student of medicine) at three individual time settings.
      Inter- and intraobserver reliability of the three classification systems were
      ascertained by computing Inter- and Intraclass (ICCs) correlation coefficients
      using Spearman's rank correlation coefficient, 95%-confidence intervals as well
      as F-tests for correlation coefficients. RESULTS: Inter- and intraobserver
      reliability for the AO classification showed a perspicuous coherence (R = 0.74
      and R = 0.79). Low to moderate intraobserver reliability for Ideberg (R = 0.46)
      and Euler classification (R = 0.41) was found. Furthermore, data show a low
      Interobserver reliability for both Ideberg and Euler classification (R < 0.2).
      Both the Inter- and Intraclass reliability using AO is significantly higher than
      those using Ideberg and Euler (p < 0.05). Using the new AO classification, it was
      possible to find a proper class for every glenoid fossa fracture. On average,
      according to Euler classification 10 of 84 fractures were not classifiable
      whereas to Ideberg classification 21 of 84 fractures were not classifiable.
      CONCLUSION: The new AO classification system introduced 2013 facilitates reliable
      grading of glenoid fossa fractures with high inter- and intraobserver reliability
      in 84 patients using CT images. It should possibly be applied in order to enable
      a valid, reliable and consistent academic description of glenoid fossa fractures.
      The established classifications by Euler and Ideberg are not capable of providing
      a similar reliability.

PMID- 29580229
TI  - Population admixture can enhance establishment success of the introduced
      biological control agent Cryptolaemus montrouzieri.
AB  - BACKGROUND: Introduced biological control agents have opportunities of population
      admixture through multiple introductions in the field. However, the importance of
      population admixture for their establishment success often remains unclear.
      Previous studies based on genetic markers have suggested a history of population
      admixture in the predatory ladybird Cryptolaemus montrouzieri Mulsant in China.
      RESULTS: We tested whether population admixture may lead to fitness changes under
      laboratory conditions. We first found no mating barrier or strong bias between
      two parental populations, despite their differences in genetics and phenotypes.
      Then, our experimental evidence supported the hypothesis that admixed populations
      have a higher potential of establishment success, due to their superior
      reproductive ability, and hunger and cold tolerance inherited from one of the
      parental populations. CONCLUSIONS: We suggest that population admixture can be a
      breeding method to improve the performance of biological control agents,
      particularly when used in a classical biological control approach, but that
      consequences for potential invasiveness need to be considered.

PMID- 29580230
TI  - Palliative care for people with schizophrenia: a qualitative study of an under
      serviced group in need.
AB  - BACKGROUND: People with schizophrenia are at risk of receiving poorer end of life
      care than other patients. They are often undertreated, avoid treatment and are
      about half as likely to access palliative care. There are limited options for end
      of life care for this under-serviced group in need. This study aims to address
      the paucity of research by documenting possible need, experiences of health care
      service use and factors affecting palliative care use for people with
      schizophrenia who have advanced life limiting illness. METHODS: Semi-structured
      interviews were undertaken with 16 experienced health professionals caring for
      people with schizophrenia in Western Australia. The interviews focussed on their
      perceptions and experiences of end of life care, their patients' unmet needs,
      palliative care options, and suggested services to support this vulnerable group
      and improve health care provision. The research used a qualitative design and
      thematic analyses. RESULTS: The participants all advocated strongly for their
      patients and recognised their extreme vulnerability. They identified a range of
      challenges and unmet needs experienced by people with schizophrenia at the end of
      life including: illness factors such as the impact of schizophrenia on
      information processing and communication; social factors such as stigma,
      isolation and the absence of a carer; and health care factors such as late
      diagnosis, delayed access to care, and mismanagement in care. Four themes were
      organised into two domains with the first exploring the individual and social
      circumstances of people with schizophrenia, including the challenges they
      experience in the health care system. The second domain covers themes that
      discuss barriers and facilitators to people with schizophrenia receiving
      palliative care and key features in palliative care provision, including
      recognising declining health, communication and planning, and collaboration and
      capacity building in the broader health, mental health and palliative care
      sectors. CONCLUSIONS: To ensure people with schizophrenia are well supported at
      the end of life a model of palliative care is required that offers both
      specialised services and capacity building within the pre-existing health
      workforce. Resources are needed to address the stigma and lack of services faced
      by this vulnerable group.

PMID- 29580231
TI  - GDF15 predict platinum response during first-line chemotherapy and can act as a
      complementary diagnostic serum biomarker with CA125 in epithelial ovarian cancer.
AB  - BACKGROUND: Growth differentiation factor 15 (GDF15) has attracted much interest
      as a novel biomarker for epithelial ovarian carcinoma (EOC). Research focus has
      been directed at GDF15 as a diagnostic detection, while the prognostic
      determination of GDF15 in EOC patients remains to be clearly elucidated. The
      present study aimed to investigate GDF15 level relative to clinicopathological
      characters, chemoresponse, and clinical outcome of EOC patients. METHODS: Serum
      from 122 patients with primary diagnosed EOC were analyzed for GDF15 and serum
      cancer antigen 125 (CA125). All cases were treated with debulking surgery and
      first-line chemotherapy, and samples were obtained just before debulking surgical
      treatment and first-line chemotherapy. Subsequently, clinical characteristics,
      responses to chemotherapy and progression-free survival (PFS) were recorded.
      RESULTS: Increasing levels of serum GDF15 was significantly associated with FIGO
      stage and lymphonodus metastasis. GDF15 and CA125 detection are complementary in
      the diagnosis of EOC and can be simultaneously profiled. The chemo-resistant EOC
      patients (median, 1225.0 pg/mL) showed significantly higher GDF15 than chemo
      sensitive patients (median, 824.2 pg/mL; P = 0.013). Highly expressed GDF15 was
      an independent negative prognostic indicator in the PFS (P = 0.026) of the 122
      EOC cases in the multivariate analysis. Additionally, patients with high level of
      serum CA125 significantly associated with suboptimal (P = 0.043) debulking
      surgery. CONCLUSIONS: Our results provide valuable evidence that GDF15 is related
      with first-line chemo-resistance, with highly expressed GDF15 being a strong and
      an independent indicator of shorter PFS in EOC patients.

PMID- 29580232
TI  - Mental disorders around cancer diagnosis and increased hospital admission rate -
      a nationwide cohort study of Swedish cancer patients.
AB  - BACKGROUND: Whether the emotional distress around cancer diagnosis is associated
      with the long-term outcomes and care utilization is unknown. We aimed to examine
      the association of mental disorders around cancer diagnosis with the hospital
      admission rates of cancer patients thereafter. METHODS: We conducted a nationwide
      cohort study including 218,508 cancer patients diagnosed in Sweden during 2004
      2009 and followed them from 90 days after cancer through 2010. We used a clinical
      diagnosis of stress-related mental disorders from 90 days before to 90 days after
      cancer diagnosis as the exposure. We studied first all hospital admissions and
      then separately three common admissions, including external injuries, infections,
      and cardiovascular diseases. The Cox model was used to estimate hazard ratios
      (HRs) with 95% confidence intervals (CIs). RESULTS: Four thousand one hundred
      five patients received a diagnosis of stress-related mental disorders around the
      cancer diagnosis, and experienced a 35% increased rate of any hospital admission
      during follow-up (HR: 1.35, 95%CI: 1.28-1.41) as well as hospital admissions for
      external injuries (HR: 1.89, 95%CI: 1.67-2.14), infections (HR: 1.28, 95%CI: 1.08
      1.52), and cardiovascular diseases (HR: 1.16, 95%CI: 1.03-1.30). Similar
      association was noted for most common cancer types. CONCLUSIONS: These data
      suggest that cancer patients diagnosed with a stress-related mental disorder
      immediately before or after cancer diagnosis are subsequently at increased risk
      of hospital admissions for major comorbidities of cancer.

PMID- 29580233
TI  - Oligohistidine and targeting peptide functionalized TAT-NLS for enhancing
      cellular uptake and promoting angiogenesis in vivo.
AB  - BACKGROUND: Gene therapy has been developed and used in medical treatment for
      many years, especially for the enhancement of endothelialization and
      angiogenesis. But slow endosomal escape rate is still one of the major barriers
      to successful gene delivery. In order to evaluate whether introducing
      oligohistidine (Hn) sequence into gene carriers can promote endosomal escape and
      gene transfection or not, we designed and synthesized Arg-Glu-Asp-Val (REDV)
      peptide functionalized TAT-NLS-Hn (TAT: typical cell-penetrating peptide, NLS:
      nuclear localization signals, Hn: oligohistidine sequence, n: 4, 8 and 12)
      peptides with different Hn sequence lengths. pEGFP-ZNF580 (pZNF580) was condensed
      by these peptides to form gene complexes, which were used to transfect human
      umbilical vein endothelial cells (HUVECs). RESULTS: MTT assay showed that the
      gene complexes exhibited low cytotoxicity for HUVECs. The results of cellular
      uptake and co-localization ratio demonstrated that the gene complexes prepared
      from TAT-NLS-Hn with long Hn sequence (n = 12) benefited for high internalization
      efficiency of pZNF580. In addition, the results of western blot analysis and PCR
      assay of REDV-TAT-NLS-H12/pZNF580 complexes showed significantly enhanced gene
      expression at protein and mRNA level. Wound healing assay and transwell migration
      assay also confirmed the improved proliferation and migration ability of the
      transfected HUVECs by these complexes. Furthermore, the in vitro and in vivo
      angiogenesis assay illustrated that these complexes could promote the tube
      formation ability of HUVECs. CONCLUSION: The above results indicated that the
      delivery efficiency of pZNF580 and its expression could be enhanced by
      introducing Hn sequence into gene carriers. The Hn sequence in REDV-TAT-NLS-Hn is
      beneficial for high gene transfection. These REDV and Hn functionalized TAT-NLS
      peptides are promising gene carriers in gene therapy.

PMID- 29580234
TI  - In vitro inhibition of porcine reproductive and respiratory syndrome virus
      replication by short antisense oligonucleotides with locked nucleic acid
      modification.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes
      porcine reproductive and respiratory syndrome (PRRS), which is currently
      insufficiently controlled. From a previous small-scale screen we identified an
      effective DNA-based short antisense oligonucleotide (AS-ON) targeting viral NSP9,
      which could inhibit PRRSV replication in both Marc-145 cells and pulmonary
      alveolar macrophages (PAMs). The objective of this study was to explore the
      strategy of incorporating locked nucleic acids (LNAs) to achieve better
      inhibition of PRRSV replication in vitro. METHODS: The effective DNA-based AS-ON
      (YN8) was modified with LNAs at both ends as gap-mer (LNA-YN8-A) or as mix-mer
      (LNA-YN8-B). Marc-145 cells or PAMs were infected with PRRSV and subsequently
      transfected. RESULTS: Compared with the DNA-based YN8 control, the two AS-ONs
      modified with LNAs were found to be significantly more effective in decreasing
      the cytopathic effect (CPE) induced by PRRSV and thus in maintaining cell
      viability. LNA modifications conferred longer lifetimes to the AS-ON in the cell
      culture model. Viral ORF7 levels were more significantly reduced at both RNA and
      protein levels as shown by quantitative PCR, western blot and indirect
      immunofluorescence staining. Moreover, transfection with LNA modified AS-ON
      reduced the PRRSV titer by 10-fold compared with the YN8 control. CONCLUSION:
      Taken together, incorporation of LNA into AS-ON technology holds higher
      therapeutic promise for PRRS control.

PMID- 29580235
TI  - Performance of in silico prediction tools for the classification of rare BRCA1/2
      missense variants in clinical diagnostics.
AB  - BACKGROUND: The use of next-generation sequencing approaches in clinical
      diagnostics has led to a tremendous increase in data and a vast number of
      variants of uncertain significance that require interpretation. Therefore,
      prediction of the effects of missense mutations using in silico tools has become
      a frequently used approach. Aim of this study was to assess the reliability of in
      silico prediction as a basis for clinical decision making in the context of
      hereditary breast and/or ovarian cancer. METHODS: We tested the performance of
      four prediction tools (Align-GVGD, SIFT, PolyPhen-2, MutationTaster2) using a set
      of 236 BRCA1/2 missense variants that had previously been classified by expert
      committees. However, a major pitfall in the creation of a reliable evaluation set
      for our purpose is the generally accepted classification of BRCA1/2 missense
      variants using the multifactorial likelihood model, which is partially based on
      Align-GVGD results. To overcome this drawback we identified 161 variants whose
      classification is independent of any previous in silico prediction. In addition
      to the performance as stand-alone tools we examined the sensitivity, specificity,
      accuracy and Matthews correlation coefficient (MCC) of combined approaches.
      RESULTS: PolyPhen-2 achieved the lowest sensitivity (0.67), specificity (0.67),
      accuracy (0.67) and MCC (0.39). Align-GVGD achieved the highest values of
      specificity (0.92), accuracy (0.92) and MCC (0.73), but was outperformed
      regarding its sensitivity (0.90) by SIFT (1.00) and MutationTaster2 (1.00). All
      tools suffered from poor specificities, resulting in an unacceptable proportion
      of false positive results in a clinical setting. This shortcoming could not be
      bypassed by combination of these tools. In the best case scenario, 138 families
      would be affected by the misclassification of neutral variants within the cohort
      of patients of the German Consortium for Hereditary Breast and Ovarian Cancer.
      CONCLUSION: We show that due to low specificities state-of-the-art in silico
      prediction tools are not suitable to predict pathogenicity of variants of
      uncertain significance in BRCA1/2. Thus, clinical consequences should never be
      based solely on in silico forecasts. However, our data suggests that SIFT and
      MutationTaster2 could be suitable to predict benignity, as both tools did not
      result in false negative predictions in our analysis.

PMID- 29580236
TI  - The FieldTrip-SimBio pipeline for EEG forward solutions.
AB  - BACKGROUND: Accurately solving the electroencephalography (EEG) forward problem
      is crucial for precise EEG source analysis. Previous studies have shown that the
      use of multicompartment head models in combination with the finite element method
      (FEM) can yield high accuracies both numerically and with regard to the
      geometrical approximation of the human head. However, the workload for the
      generation of multicompartment head models has often been too high and the use of
      publicly available FEM implementations too complicated for a wider application of
      FEM in research studies. In this paper, we present a MATLAB-based pipeline that
      aims to resolve this lack of easy-to-use integrated software solutions. The
      presented pipeline allows for the easy application of five-compartment head
      models with the FEM within the FieldTrip toolbox for EEG source analysis.
      METHODS: The FEM from the SimBio toolbox, more specifically the St. Venant
      approach, was integrated into the FieldTrip toolbox. We give a short sketch of
      the implementation and its application, and we perform a source localization of
      somatosensory evoked potentials (SEPs) using this pipeline. We then evaluate the
      accuracy that can be achieved using the automatically generated five-compartment
      hexahedral head model [skin, skull, cerebrospinal fluid (CSF), gray matter, white
      matter] in comparison to a highly accurate tetrahedral head model that was
      generated on the basis of a semiautomatic segmentation with very careful and time
      consuming manual corrections. RESULTS: The source analysis of the SEP data
      correctly localizes the P20 component and achieves a high goodness of fit. The
      subsequent comparison to the highly detailed tetrahedral head model shows that
      the automatically generated five-compartment head model performs about as well as
      a highly detailed four-compartment head model (skin, skull, CSF, brain). This is
      a significant improvement in comparison to a three-compartment head model, which
      is frequently used in praxis, since the importance of modeling the CSF
      compartment has been shown in a variety of studies. CONCLUSION: The presented
      pipeline facilitates the use of five-compartment head models with the FEM for EEG
      source analysis. The accuracy with which the EEG forward problem can thereby be
      solved is increased compared to the commonly used three-compartment head models,
      and more reliable EEG source reconstruction results can be obtained.

PMID- 29580237
TI  - Assessment of population coverage of hypertension screening in Thailand based on
      the effective coverage framework.
AB  - BACKGROUND: Hypertension (HT) is a major risk factor, and accessible and
      effective HT screening services are necessary. The effective coverage framework
      is an assessment tool that can be used to assess health service performance by
      considering target population who need and receive quality service. The aim of
      this study is to measure effective coverage of hypertension screening services at
      the provincial level in Thailand. METHODS: Over 40 million individual health
      service records in 2013 were acquired. Data on blood pressure measurement, risk
      assessment, HT diagnosis and follow up were analyzed. The effectiveness of the
      services was assessed based on a set of quality criteria for pre-HT, suspected
      HT, and confirmed HT cases. Effective coverage of HT services for all non-HT Thai
      population aged 15 or over was estimated for each province and for all Thailand.
      RESULTS: Population coverage of HT screening is 54.6%, varying significantly
      across provinces. Among those screened, 28.9% were considered pre-HT, and another
      6.0% were suspected HT cases. The average provincial effective coverage was at
      49.9%. Around four-fifths (82.6%) of the pre-HT group received HT and
      Cardiovascular diseases (CVD) risk assessment. Among the suspected HT cases, less
      than half (38.0%) got a follow-up blood pressure measurement within 60 days from
      the screening date. Around 9.2% of the suspected cases were diagnosed as having
      HT, and only one-third of them (36.5%) received treatment within 6 months. Within
      this group, 21.8% obtained CVD risk assessment, and half of them had their blood
      pressure under control (50.8%) with less than 1 % (0.7%) of them managed to get
      the CVD risk reduced. CONCLUSIONS: Our findings suggest that hypertension
      screening coverage, post-screening service quality, and effective coverage of HT
      screening in Thailand were still low and they vary greatly across provinces. It
      is imperative that service coverage and its effectiveness are assessed, and both
      need improvement. Despite some limitations, measurement of effective coverage
      could be done with existing data, and it can serve as a useful tool for
      performance measurement of public health services.

PMID- 29580238
TI  - The effectiveness of treatment for Severe Acute Malnutrition (SAM) delivered by
      community health workers compared to a traditional facility based model.
AB  - BACKGROUND: In most health systems, Community Health Workers (CHWs) identify and
      screen for severe acute malnutrition (SAM) in the community. This study aimed to
      investigate the potential of integrating SAM identification and treatment
      delivered by CHWs, in order to improve the coverage of SAM treatment services.
      METHODS: This multicentre, randomised intervention study was conducted in Kita,
      Southwest Mali between February 2015 and February 2016. Treatment for
      uncomplicated SAM was provided in health facilities in the control area, and by
      Community Health Workers and health facilities in the intervention area. Clinical
      outcomes (cure, death and defaulter ratios), treatment coverage and quality of
      care were examined in both the control and intervention group. RESULTS: Six
      hundred ninety nine children were admitted to the intervention group and 235
      children to the control group. The intervention group reported cure ratios of
      94.2% compared to 88.6% in the control group (risk ratio 1.07 [95% CI 1.01;
      1.13]). Defaulter ratios were twice as high in the control group compared to the
      intervention group (10.8% vs 4.5%; RR 0.42 [95% CI 0.25; 0.71]). Differences in
      mortality ratios were not statistically significant (0.9% in the intervention
      group compared to 0.8% in the control group). Coverage rates in December 2015
      were 86.7% in intervention group compared to 41.6% in the control (p < 0.0001).
      CONCLUSIONS: With minimal training, CHWs are able to appropriately treat SAM in
      the community. Allowing CHWs to treat SAM reduces defaulter ratios without
      compromising treatment outcomes and can lead to improved access to treatment.
      TRIAL REGISTRATION: Retrospectively registered in ISRCTN Register with
      ISRCTN33578874 on March 7th 2018.

PMID- 29580239
TI  - Is double-approach surgery and tenodesis without a gastrocnemius flap better for
      dealing with proximal fibular osteosarcoma?
AB  - BACKGROUND: Resection of proximal fibular osteosarcoma involving the
      posteromedial aspect of the fibula is challenging. Reconstruction using a
      gastrocnemius flap may result in significant lateral instability and abnormal
      knee movement. Furthermore, postoperative gait may be disturbed by foot drop
      resulting from scarification of the common peroneal nerve. METHODS: Between
      January 2011 and December 2013, five patients with proximal fibular osteosarcoma
      were treated via the double-approach procedure using en bloc resection without a
      gastrocnemius flap. Simultaneously, all patients received one-stage tenodesis of
      the anterior tibial and toe extensor tendons. Clinical outcomes, including local
      tumor recurrence, complications, and functional outcomes, were evaluated.
      RESULTS: The mean follow-up duration was 47.2 months (range 42-52 months). No
      patients experienced local recurrence. The patients' Enneking functional scores
      were excellent (80%) or good (20%) at the final follow-up. CONCLUSIONS: In
      patients with proximal fibular osteosarcoma, the double-approach procedure allows
      easier and safer en bloc tumor resection with vessel and nerve protection. One
      stage tenodesis without a gastrocnemius flap is associated with good functional
      outcomes.

PMID- 29580240
TI  - Exploring native genetic elements as plug-in tools for synthetic biology in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - BACKGROUND: The unicellular cyanobacterium Synechocystis sp. PCC 6803 has been
      widely used as a photoautotrophic host for synthetic biology studies. However, as
      a green chassis to capture CO2 for biotechnological applications, the genetic
      toolbox for Synechocystis 6803 is still a limited factor. RESULTS: We
      systematically characterized endogenous genetic elements of Synechocystis 6803,
      including promoters, ribosome binding sites, transcription terminators, and
      plasmids. Expression from twelve native promoters was compared by measuring
      fluorescence from the reporter protein EYFP in an identical setup, exhibiting an
      8000-fold range of promoter activities. Moreover, we measured the strength of
      twenty native ribosome binding sites and eight native terminators, indicating
      their influence on the expression of the reporter genes. In addition, two shuttle
      vectors, pCA-UC118 and pCB-SC101, capable of replication in both Synechocystis
      6803 and E. coli were constructed. Expression of reporter proteins were
      significantly enhanced in cells containing these new plasmids, thus providing
      superior gene expression platforms in this cyanobacterium. CONCLUSIONS: The
      results of this study provide useful and well characterized native tools for
      bioengineering work in the model cyanobacterium Synechocystis 6803.

PMID- 29580241
TI  - Enhanced expression of histone chaperone APLF associate with breast cancer.
AB  - DNA damage-specific histone chaperone Aprataxin PNK-like factor (APLF) regulates
      mesenchymal-to-epithelial transition (MET) during cellular reprogramming. We
      investigated the role of APLF in epithelial-to-mesenchymal transition (EMT)
      linked to breast cancer invasiveness and metastasis. Here, we show that a
      significant manifestation of APLF is present in tumor sections of patients with
      invasive ductal carcinoma when compared to their normal adjacent tissues. APLF
      was significantly induced in triple negative breast cancer (TNBC) cells, MDAMB
      231, in comparison to invasive MCF7 or normal MCF10A breast cells and supported
      by studies on invasive breast carcinoma in The Cancer Genome Atlas (TCGA).
      Functionally, APLF downregulation inhibited proliferative capacity, altered cell
      cycle behavior, induced apoptosis and impaired DNA repair ability of MDAMB-231
      cells. Reduction in APLF level impeded invasive, migratory, tumorigenic and
      metastatic potential of TNBC cells with loss in expression of genes associated
      with EMT while upregulation of MET-specific gene E-cadherin (CDH1). So, here we
      provided novel evidence for enrichment of APLF in breast tumors, which could
      regulate metastasis-associated EMT in invasive breast cancer. We anticipate that
      APLF could be exploited as a biomarker for breast tumors and additionally could
      be targeted in sensitizing cancer cells towards DNA damaging agents.

PMID- 29580242
TI  - Plasma procalcitonin concentrations predict organ dysfunction and outcome in dogs
      with sepsis.
AB  - BACKGROUND: Procalcitonin (PCT) is a valuable prognostic biomarker in human
      sepsis that is predictive of organ dysfunction, septic shock and mortality. Data
      on PCT in dogs is limited. This study aimed to investigate the prognostic value
      of baseline and serial PCT measurements in dogs with sepsis and to determine the
      association between PCT and sepsis severity and the presence of organ
      dysfunction. PCT concentrations were measured in citrated plasma samples
      collected from 53 dogs with sepsis at the time of admission (T0, n = 53) and at
      24 h (T1, n = 35) and 48 h (T2, n = 30) post-admission using a commercial ELISA.
      Dogs were classified by sepsis severity (sepsis without organ dysfunction; severe
      sepsis; septic shock) and outcome (survivors; non-survivors). Organ dysfunctions
      were recorded at T0 and during hospitalization, and the APPLEfast score
      calculated at T0. Healthy dogs (n = 12) were used as controls. RESULTS: There
      were 18 septic dogs without organ dysfunction, 24 dogs with severe sepsis and 11
      with septic shock. Baseline PCT concentrations were significantly greater in dogs
      with sepsis compared to healthy controls (P < 0.0001), and in dogs with septic
      shock compared to dogs without cardiovascular compromise (P = 0.01). Baseline PCT
      was significantly correlated with organ dysfunction (P = 0.003). Declining PCT
      concentrations were documented in survivors at T1 and T2 compared to PCT at T0 (P
      = 0.0006), and PCT clearance at 24 h was significantly higher in survivors (n =
      38) compared to non-survivors (n = 15) (P = 0.037). Canine APPLEfast score was
      not predictive of sepsis severity, the development of MODS or outcome.
      CONCLUSION: In dogs with sepsis, PCT concentrations at hospital admissions are
      predictive of organ dysfunction and septic shock. Serial procalcitonin monitoring
      may offer valuable prognostic information in canine sepsis, wherein early
      decreases in PCT concentrations are associated with survival.

PMID- 29580243
TI  - Factors associated with the use of cognitive aids in operating room crises: a
      cross-sectional study of US hospitals and ambulatory surgical centers.
AB  - BACKGROUND: Operating room (OR) crises are high-acuity events requiring rapid,
      coordinated management. Medical judgment and decision-making can be compromised
      in stressful situations, and clinicians may not experience a crisis for many
      years. A cognitive aid (e.g., checklist) for the most common types of crises in
      the OR may improve management during unexpected and rare events. While
      implementation strategies for innovations such as cognitive aids for routine use
      are becoming better understood, cognitive aids that are rarely used are not yet
      well understood. We examined organizational context and implementation process
      factors influencing the use of cognitive aids for OR crises. METHODS: We
      conducted a cross-sectional study using a Web-based survey of individuals who had
      downloaded OR cognitive aids from the websites of Ariadne Labs or Stanford
      University between January 2013 and January 2016. In this paper, we report on the
      experience of 368 respondents from US hospitals and ambulatory surgical centers.
      We analyzed the relationship of more successful implementation (measured as
      reported regular cognitive aid use during applicable clinical events) with
      organizational context and with participation in a multi-step implementation
      process. We used multivariable logistic regression to identify significant
      predictors of reported, regular OR cognitive aid use during OR crises. RESULTS:
      In the multivariable logistic regression, small facility size was associated with
      a fourfold increase in the odds of a facility reporting more successful
      implementation (p = 0.0092). Completing more implementation steps was also
      significantly associated with more successful implementation; each implementation
      step completed was associated with just over 50% higher odds of more successful
      implementation (p <= 0.0001). More successful implementation was associated with
      leadership support (p < 0.0001) and dedicated time to train staff (p = 0.0189).
      Less successful implementation was associated with resistance among clinical
      providers to using cognitive aids (p < 0.0001), absence of an implementation
      champion (p = 0.0126), and unsatisfactory content or design of the cognitive aid
      (p = 0.0112). CONCLUSIONS: Successful implementation of cognitive aids in ORs was
      associated with a supportive organizational context and following a multi-step
      implementation process. Building strong organizational support and following a
      well-planned multi-step implementation process will likely increase the use of OR
      cognitive aids during intraoperative crises, which may improve patient outcomes.

PMID- 29580244
TI  - Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance
      associated mutations in the Colombian Amazonian region.
AB  - BACKGROUND: Malaria continues being a public health problem worldwide. Plasmodium
      vivax is the species causing the largest number of cases of malaria in Asia and
      South America. Due to the lack of a completely effective anti-malarial vaccine,
      controlling this disease has been based on transmission vector management, rapid
      diagnosis and suitable treatment. However, parasite resistance to anti-malarial
      drugs has become a major yet-to-be-overcome challenge. This study was thus aimed
      at determining pvmdr1, pvdhfr, pvdhps and pvcrt-o gene mutations and haplotypes
      from field samples obtained from an endemic area in the Colombian Amazonian
      region. METHODS: Fifty samples of parasite DNA infected by a single P. vivax
      strain from symptomatic patients from the Amazonas department in Colombia were
      analysed by PCR and the pvdhfr, pvdhps, pvmdr1 and pvcrt-o genes were sequenced.
      Diversity estimators were calculated from the sequences and the haplotypes
      circulating in the Colombian Amazonian region were obtained. CONCLUSION: pvdhfr,
      pvdhps, pvmdr1 and pvcrt-o genes in the Colombian Amazonian region are
      characterized by low genetic diversity. Some resistance-associated mutations were
      found circulating in this population. New variants are also being reported. A
      selective sweep signal was located in pvdhfr and pvmdr1 genes, suggesting that
      these mutations (or some of them) could be providing an adaptive advantage.

PMID- 29580245
TI  - The clinical relevance of advanced artificial feedback in the control of a multi
      functional myoelectric prosthesis.
AB  - BACKGROUND: To effectively replace the human hand, a prosthesis should seamlessly
      respond to user intentions but also convey sensory information back to the user.
      Restoration of sensory feedback is rated highly by the prosthesis users, and
      feedback is critical for grasping in able-bodied subjects. Nonetheless, the
      benefits of feedback in prosthetics are still debated. The lack of consensus is
      likely due to the complex nature of sensory feedback during prosthesis control,
      so that its effectiveness depends on multiple factors (e.g., task complexity,
      user learning). METHODS: We evaluated the impact of these factors with a
      longitudinal assessment in six amputee subjects, using a clinical setup (socket,
      embedded control) and a range of tasks (box and blocks, block turn, clothespin
      and cups relocation). To provide feedback, we have proposed a novel vibrotactile
      stimulation scheme capable of transmitting multiple variables from a
      multifunction prosthesis. The subjects wore a bracelet with four by two uniformly
      placed vibro-tactors providing information on contact, prosthesis state (active
      function), and grasping force. The subjects also completed a questionnaire for
      the subjective evaluation of the feedback. RESULTS: The tests demonstrated that
      feedback was beneficial only in the complex tasks (block turn, clothespin and
      cups relocation), and that the training had an important, task-dependent impact.
      In the clothespin relocation and block turn tasks, training allowed the subjects
      to establish successful feedforward control, and therefore, the feedback became
      redundant. In the cups relocation task, however, the subjects needed some
      training to learn how to properly exploit the feedback. The subjective evaluation
      of the feedback was consistently positive, regardless of the objective benefits.
      These results underline the multifaceted nature of closed-loop prosthesis control
      as, depending on the context, the same feedback interface can have different
      impact on performance. Finally, even if the closed-loop control does not improve
      the performance, it could be beneficial as it seems to improve the subjective
      experience. CONCLUSIONS: Therefore, in this study we demonstrate, for the first
      time, the relevance of an advanced, multi-variable feedback interface for
      dexterous, multi-functional prosthesis control in a clinically relevant setting.

PMID- 29580246
TI  - Correction to: A randomized controlled trial of an intervention delivered by
      mobile phone app instant messaging to increase the acceptability of effective
      contraception among young people in Tajikistan.
AB  - After publication of the original article [1], it came to the authors' attention
      that there is a typo in the Results section.

PMID- 29580247
TI  - Nationwide insecticide resistance status and biting behaviour of malaria vector
      species in the Democratic Republic of Congo.
AB  - BACKGROUND: Globally, the Democratic Republic of Congo (DRC) accounted for 9% of
      malaria cases and 10% of malaria deaths in 2015. As part of control efforts, more
      than 40 million long-lasting insecticidal nets (LLINs) were distributed between
      2008 and 2013, resulting in 70% of households owning one or more LLINs in 2014.
      To optimize vector control efforts, it is critical to monitor vector behaviour
      and insecticide resistance trends. Entomological data was collected from eight
      sentinel sites throughout DRC between 2013 and 2016 in Kingasani, Mikalayi,
      Lodja, Kabondo, Katana, Kapolowe, Tshikaji and Kalemie. Mosquito species present,
      relative densities and biting times were monitored using human landing catches
      (HLC) conducted in eight houses, three times per year. HLC was conducted monthly
      in Lodja and Kapolowe during 2016 to assess seasonal dynamics. Laboratory data
      included resistance mechanism frequency and sporozoite rates. Insecticide
      susceptibility testing was conducted with commonly used insecticides including
      deltamethrin and permethrin. Synergist bioassays were conducted with PBO to
      determine the role of oxidases in permethrin resistance. RESULTS: In Lodja,
      monthly Anopheles gambiae s.l. biting rates were consistently high at > 10
      bites/person/night indoors and outdoors. In Kapolowe, An. gambiae s.l. dominated
      during the rainy season, and Anopheles funestus s.l. during the dry season. In
      all sites, An. gambiae and An. funestus biting occurred mostly late at night. In
      Kapolowe, significant biting of both species started around 19:00, typically
      before householders use nets. Sporozoite rates were high, with a mean of 4.3%
      (95% CI 3.4-5.2) for An. gambiae and 3.3% (95% CI 1.3-5.3) for An. funestus.
      Anopheles gambiae were resistant to permethrin in six out of seven sites in 2016.
      In three sites, susceptibility to deltamethrin was observed despite high
      frequency permethrin resistance, indicating the presence of pyrethroid-specific
      resistance mechanisms. Pre-exposure to PBO increased absolute permethrin
      associated mortality by 24%, indicating that resistance was partly due to
      metabolic mechanisms. The kdr-1014F mutation in An. gambiae was present at high
      frequency (> 70%) in three sites (Kabondo, Kingasani and Tshikaji), and lower
      frequency (< 20%) in two sites (Lodja and Kapolowe). CONCLUSION: The finding of
      widespread resistance to permethrin in DRC is concerning and alternative
      insecticides should be evaluated.

PMID- 29580248
TI  - Knockdown of IFI27 inhibits cell proliferation and invasion in oral squamous cell
      carcinoma.
AB  - BACKGROUND: The development of oral squamous cell carcinoma (OSCC) involves
      genetic mutations, epigenetic gene expression modification, and other processes.
      It has been reported that IFI27 is upregulated in OSCC, but its function is
      unknown. The aim of this study was to investigate the role of IFI27 on OSCC cell
      proliferation and invasion. METHODS: The protein level of IFI27 in OSCC tissues
      and adjacent tissues was detected by immunohistochemistry. In the OSCC cell
      model, we designed the IFI27 siRNA to downregulate the expression of IFI27; gene
      and protein of IFI27 in those models were then detected by Q-PCR and Western
      blot. MTT assay was used to detect the effect of -IFI27 knockdown on cell
      proliferation; Annexin V-PI staining flow cytometry was used to detect the effect
      of IFI27 downregulation on apoptosis of cancer cells. The effect of IFI27
      downregulation on oral cancer cell invasion was detected using Transwell assay.
      RESULTS: IFI27 was highly expressed in OSCC tissues by immunohistochemical assay.
      In the OSCC cell model, IFI27 siRNA could downregulate the mRNA and protein
      expression level of IFI27. As showed in MTT assay, Annexin V-PI assay, and
      Transwell assay, through the downregulation of IFI27, TSCCA and TCA8113 cell
      proliferation were inhibited, OSCC cell apoptosis was promoted, and its migration
      and invasion were inhibited. CONCLUSION: IFI27 is involved in the development and
      progression of OSCC. Its high expression promotes cell proliferation and invasion
      and reduces apoptosis. These findings may provide new biomarkers and therapeutic
      targets for OSCC diagnosis and clinical treatment.

PMID- 29580249
TI  - Evaluation of a program for routine implementation of shared decision-making in
      cancer care: study protocol of a stepped wedge cluster randomized trial.
AB  - BACKGROUND: Shared decision-making (SDM) has become increasingly important in
      health care. However, despite scientific evidence, effective implementation
      strategies, and a prominent position on the health policy agenda, SDM is not
      widely implemented in routine practice so far. Therefore, we developed a program
      for routine implementation of SDM in oncology by conducting an analysis of the
      current state and a needs assessment in a pilot study based on the Consolidated
      Framework for Implementation Research (CFIR). Based on these results, the main
      aim of our current study is to evaluate the process and outcome of this
      theoretically and empirically grounded multicomponent implementation program
      designed to foster SDM in routine cancer care. METHODS: We use a stepped wedge
      design, a variant of the cluster randomized controlled trial. The intervention to
      be implemented is SDM. Three participating clinics of one comprehensive cancer
      center will be randomized and receive the multicomponent SDM implementation
      program in a time-delayed sequence. The program consists of the following
      strategies: (a) SDM training for health care professionals, (b) individual
      coaching for physicians, (c) patient activation strategy, (d) provision of
      patient information material and decision aids, (e) revision of the clinics'
      quality management documents, and (f) critical reflection of current organization
      of multidisciplinary team meetings. We will conduct a mixed methods outcome and
      process evaluation. The outcome evaluation will consist of four measurement
      points. The primary outcome is adoption of SDM, measured by the 9-item Shared
      Decision Making Questionnaire. A range of other implementation outcomes will be
      assessed (i.e., acceptability, readiness for implementing change,
      appropriateness, penetration). The implementation process will be evaluated using
      stakeholder interviews and field notes. This will allow adapting interventions if
      necessary. DISCUSSION: This study is the first large study on routine
      implementation of SDM conducted in German cancer care. We expect to foster
      implementation of SDM at the enrolled clinics. Insights gained from this study,
      using a theoretically and empirically grounded approach, can inform other SDM
      implementation studies and health policy developments, both nationally and
      internationally. TRIAL REGISTRATION: clinicaltrials.gov, NCT03393351 . Registered
      8 January 2018.

PMID- 29580250
TI  - Effectiveness of Omega-3 fatty acid for polycystic ovary syndrome: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness and safety of omega-3 fatty acid for
      patients with PCOS. METHODS: In this meta-analysis, data from randomized
      controlled trials were obtained to assess the effects of omega-3 fatty acid
      versus placebo or western medicine in women with PCOS. The study's registration
      number is CRD42017065859. The primary outcomes included the change of homeostatic
      model assessment (HOMA) of insulin resistance, total cholesterol (TC),
      triglyceride (TG) and adiponectin. RESULT: Nine trials involving 591 patients
      were included. Comparing with the control group, omega-3 fatty acid may improve
      HOMA index (WMD -0.80; 95% CI -0.89, - 0.71; P<0. 00001), decrease TC and TG
      level [TC: (WMD -9.43; 95% CI -11.90, - 6.95; P<0. 00001); TG: (WMD -29.21; 95%
      CI -48.08, - 10.34; P = 0. 002)], and increase adiponectin level (WMD 1.34; 95%
      CI 0.51, 2.17; P = 0. 002). CONCLUSION: Based on current evidence, omega-3 fatty
      acid may be recommended for the treatment of PCOS with insulin resistance as well
      as high TC (especially LDL-C) and TG.

PMID- 29580252
TI  - Early musculoskeletal classroom education confers little advantage to medical
      student knowledge and competency in the absence of clinical experiences: a
      retrospective comparison study.
AB  - BACKGROUND: Deficiencies in medical student knowledge in musculoskeletal medicine
      have been well documented. To address these deficiencies, numerous curricular
      changes at our institution were instituted. The objective of this study was to
      determine whether medical students in their preclinical years benefit from early
      exposure to musculoskeletal medicine when compared to students exposed to
      musculoskeletal medicine just prior to completion of their preclinical
      curriculum. METHODS: United States Medical Licensing Examination (USMLE) Step 1
      and 2 scores were compared for periods of time before and after institution of
      the new curriculum. Scores on the previously validated 24-question short answer
      survey from Freedman and Bernstein were also compared over these same periods of
      time between these two groups and to established standards for competency, using
      a student's two-tailed unpaired t-test for significance. Entering Medical College
      Admission Test (MCAT) scores were used to compare baseline preparation of
      students. RESULTS: Overall USMLE scores as well as scores on the USMLE subtest on
      Musculoskeletal, Skin and Connective Tissue Disease showed no improvement when
      scores were compared between the two groups of students. There was a
      statistically significant lower performance on the Freedman and Bernstein
      knowledge assessment exam for students in the new pre-clinical curriculum as
      compared to those introduced under the old model, considering both
      musculoskeletal knowledge (p < 0.001) and proficiency (p < 0.01), though the
      response rate on the recent survey was low (112/986 or 11%). Spine remained the
      least understood sub-topic, while a dedicated course in rheumatology likely
      contributed to increased student knowledge in that area. Additional exposure to
      musculoskeletal topics during the clinical years increased student knowledge.
      There was no difference between groups when comparing entering MCAT scores.
      CONCLUSIONS: Classroom curricular changes, including moving the introductory
      musculoskeletal course to the first year, intended to optimize musculoskeletal
      medicine education in the pre-clinical years of medical school did not appear to
      improve student musculoskeletal knowledge at any year of training. Further
      efforts to improve the education of medical students in musculoskeletal medicine
      should be directed towards providing more clinical experiences with patients
      having musculoskeletal concerns. This was a retrospective comparative study,
      level III evidence.

PMID- 29580251
TI  - Defining the external implementation context: an integrative systematic
      literature review.
AB  - BACKGROUND: Proper implementation of evidence-based interventions is necessary
      for their full impact to be realized. However, the majority of research to date
      has overlooked facilitators and barriers existing outside the boundaries of the
      implementing organization(s). Better understanding and measurement of the
      external implementation context would be particularly beneficial in light of
      complex health interventions that extend into and interact with the larger
      environment they are embedded within. We conducted a integrative systematic
      literature review to identify external context constructs likely to impact
      implementation of complex evidence-based interventions. METHODS: The review
      process was iterative due to our goal to inductively develop the identified
      constructs. Data collection occurred in four primary stages: (1) an initial set
      of key literature across disciplines was identified and used to inform (2)
      journal and (3) author searches that, in turn, informed the design of the final
      (4) database search. Additionally, (5) we conducted citation searches of relevant
      literature reviews identified in each stage. We carried out an inductive thematic
      content analysis with the goal of developing homogenous, well-defined, and
      mutually exclusive categories. RESULTS: We identified eight external context
      constructs: (1) professional influences, (2) political support, (3) social
      climate, (4) local infrastructure, (5) policy and legal climate, (6) relational
      climate, (7) target population, and (8) funding and economic climate.
      CONCLUSIONS: This is the first study to our knowledge to use a systematic review
      process to identify empirically observed external context factors documented to
      impact implementation. Comparison with four widely-utilized implementation
      frameworks supports the exhaustiveness of our review process. Future work should
      focus on the development of more stringent operationalization and measurement of
      these external constructs.

PMID- 29580253
TI  - Excessive nerve growth factor impairs bidirectional communication between the
      oocyte and cumulus cells resulting in reduced oocyte competence.
AB  - BACKGROUND: Excessive nerve growth factor (NGF) is commonly found in the
      follicular fluid of patients with polycystic ovary syndrome (PCOS). Furthermore,
      oocytes from PCOS patients exhibit lower developmental competence. The purpose of
      this study was to explore the association between excessive NGF and low oocyte
      competence in vitro. METHODS: Excessive NGF was added to mouse cumulus oocyte
      complexes (COCs) cultured in vitro to investigate meiotic maturation of the
      oocyte. After culture, mRNA expression levels of Pfkp and Ldha genes in cumulus
      cells (CCs) and Gdf9, Bmp15 and Fgf8 genes in oocytes, were determined by real
      time quantitative polymerase chain reaction (qPCR). We also investigated the mRNA
      content of Pfkp and Ldha in CCs from PCOS and non-PCOS patients. RESULTS:
      Excessive NGF significantly inhibited oocyte meiotic maturation. The inhibitory
      effect was mediated by the NGF high-affinity receptor, NTRK1. mRNA content of
      Pfkp and Ldha genes in CCs was significantly reduced by excessive NGF
      stimulation. Moreover, the expression levels of Gdf9, Bmp15 and Fgf8 were also
      decreased in oocytes, and was induced by excessive NGF-stimulated CCs. In
      addition, lower expression levels of Pfkp and Ldha in CCs were identified in
      Chinese PCOS patients with excessive NGF (PCOS, 22 +/- 2.63 ng/ml, n = 13; non
      PCOS, 7.18 +/- 2.42 ng/ml, n = 9; p < 0.01) in the follicular fluid, suggesting a
      potential association between excessive NGF and decreased glycolysis in the CCs
      of women with PCOS. CONCLUSIONS: Excessive NGF impairs bidirectional
      communication between oocyte and cumulus cells, which might be related to low
      oocyte competence.

PMID- 29580254
TI  - Implementation of surgical debriefing programs in large health systems: an
      exploratory qualitative analysis.
AB  - BACKGROUND: The role of the "debrief" to address issues related to patient safety
      and systematic flaws in care is frequently overlooked. In our study, we interview
      surgical leaders who have developed successful strategies of debriefing within a
      comprehensive program of quality improvement. METHODS: Semi-structured interviews
      of four implementation leaders were performed. The observations, beliefs and
      strategies of surgical leaders are compared and contrasted. Common themes are
      identified related to program success and failure. Quality and safety researchers
      performed, coded and categorized the interviews and coordinated the analysis and
      interpretation of the results. The authors from the four institutions aided in
      interpretation and framing of the results. RESULTS: The debriefing programs
      evaluated were part of comprehensive quality improvement projects. Seven high
      level themes and 24 subthemes were identified from the interviews. Themes related
      to leadership included early engagement, visible ongoing commitment and
      enforcement. Success appeared to depend upon meaningful and early debriefing
      feedback. The culture of safety that promoted success included a commitment to
      open and fair communication and continuous improvement. There were many
      challenges to the success of debriefing programs. The loss of institutional
      commitment of resources and personnel was the instigating factor behind the
      collapse of the program at Michigan. Other areas of potential failure included
      communication issues and loss of early and meaningful feedback. CONCLUSIONS:
      Leaders of four surgical systems with strong debriefing programs report success
      using debriefing to improve system performance. These findings are consistent
      with previously published studies. Success requires commitment of resources, and
      leadership engagement. The greatest gains may be best achieved by programs that
      provide meaningful debriefing feedback in an atmosphere dedicated to open
      communication.

PMID- 29580255
TI  - Total energy expenditure in adults aged 65 years and over measured using doubly
      labelled water: international data availability and opportunities for data
      sharing.
AB  - BACKGROUND: Increasing population lifespan necessitates a greater understanding
      of nutritional needs in older adults (65 year and over). A synthesis of total
      energy expenditure in the older population has not been undertaken and is needed
      to inform nutritional requirements. We aimed to establish the extent of the
      international evidence for total energy expenditure (TEE) using doubly-labelled
      water (DLW) in older adults (65 years and over), report challenges in obtaining
      primary data, and make recommendations for future data sharing. METHODS: Four
      databases were searched to identify eligible studies; original research of any
      study design where participant level TEE was measured using DLW in participants
      aged >=65 years. Once studies were identified for inclusion, authors were
      contacted where data were not publicly available. RESULTS: Screening was
      undertaken of 1223 records; the review of 317 full text papers excluded 170
      records. Corresponding or first authors of 147 eligible studies were contacted
      electronically. Participant level data were publicly available or provided by
      authors for 45 publications (890 participants aged >=65 years, with 248 aged >=80
      years). Sixty-seven percent of the DLW data in this population were unavailable
      due to authors unable to be contacted or declining to participate, or data being
      irretrievable. CONCLUSIONS: The lack of data access limits the value of the
      original research and its contribution to nutrition science. Openly accessible
      DLW data available through publications or a new international data repository
      would facilitate greater integration of current research with previous findings
      and ensure evidence is available to support the needs of the ageing population.
      TRIAL REGISTRATION: The protocol was registered with the International
      Prospective Register of Systematic Reviews (PROSPERO), registration number
      CRD42016047549 .

PMID- 29580256
TI  - Utilization of institutional delivery service and associated factors among
      mothers in North West Ethiopian.
AB  - OBJECTIVE: The aim of this study was to assess institutional delivery and its
      associated factors in Benishangul-Gumez region, North-West of Ethiopia. The data
      were obtained at community level in a single survey within 1 month and there is
      no continuation of this study or previously published part elsewhere. RESULTS:
      Among the 428 eligible respondents recruited for this study, 427 of them
      responded completely to the interview, giving a response rate of 99.8%. Of the
      total (427) respondents, 51.1% women delivered the recent child at health
      facility in the 12 months preceding the survey. Among the common reasons for home
      delivery were, labour was urgent (25.8%), home birth was usual habit for them
      (23.9%) and distance to health center was too far. Age (AOR = 3.4, 95% CI 1.46,
      7.97), husband occupation (AOR = 5.16, 95% CI 1.74, 15.31), frequency of
      antenatal care visit (AOR = 3.34, 95% CI 1.88, 5.94) and maternal knowledge on
      danger signs of pregnancy and delivery (AOR = 7.18, 95% CI 3.77, 13.66) were
      significantly associated factors with institutional delivery. Although, the
      prevalence of institutional delivery has improved when compared to previous
      reports, strategic modification is important to increase health facility
      delivery.

PMID- 29580259
TI  - Correction to: Redefining mouse transgenesis with CRISPR/Cas9 genome editing
      technology.
AB  - CORRECTION: In the recent Research Highlight [1], it has been highlighted that
      part b of Fig. 1 was incorrectly labelled as "sgRNA + tracrRNA" instead of "sgRNA
      (crRNA + tracrRNA)". An updated Figure 1, including also the amended figure
      legend has therefore been provided below.

PMID- 29580257
TI  - Gut microbiome modulates efficacy of immune checkpoint inhibitors.
AB  - Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer
      treatments in recent years. However, it was observed that most patients treated
      with ICIs could not get benefit from the therapy, which led to the limitation of
      clinical application. Motivated by potent and durable efficacy of ICIs,
      oncologists endeavor to explore the mechanisms of resistance to ICIs and increase
      the drug sensitivity. It is known that heterogeneity of gut microbiome in
      populations may result in different outcomes of therapy. In xenograft model,
      bacteria in gut have been proved as a crucial factor regulating immunotherapy
      efficacy. And the similar phenomenon was obtained in patients. In this review, we
      summarized relevant advancements about gut microbiome and ICIs. Furthermore, we
      focused on modulatory function of gut microbiome in ICIs therapy and possible
      antitumor mechanism of specific commensals in ICIs treatment. We propose that gut
      microbiome is an important predictive factor, and manipulation of gut microbiome
      is feasible to elevate response rate in ICIs therapy.

PMID- 29580258
TI  - Detection of Creutzfeldt-Jakob disease prions in skin: implications for
      healthcare.
AB  - Evidence has recently been reported of prion seeding activity in skin tissue from
      patients with sporadic Creutzfeldt-Jakob disease (sCJD). This is relevant
      information for infection control measures during surgery. The work uses very
      sensitive prion assays now available for medical research, and may soon be
      adapted to related neurodegenerative disorders.

PMID- 29580260
TI  - Systematic Techniques to Enhance rEtention in Randomised controlled trials: the
      STEER study protocol.
AB  - BACKGROUND: Non-retention of participants seriously affects the credibility of
      clinical trial results and significantly reduces the potential of a trial to
      influence clinical practice. Non-retention can be defined as instances where
      participants leave the study prematurely. Examples include withdrawal of consent
      and loss to follow-up and thus outcome data cannot be obtained. The majority of
      existing interventions targeting retention fail to describe any theoretical basis
      for the observed improvement, or lack of improvement. Moreover, most of these
      interventions lack involvement of participants in their conception and/or design,
      raising questions about their relevance and acceptability. Many of the causes of
      non-retention involve people performing a behaviour (e.g. not returning a
      questionnaire). Behaviour change is difficult, and the importance of a strong
      theoretical basis for interventions that aim to change behaviour is increasingly
      recognised. This research aims to develop and pilot theoretically informed,
      participant-centred, evidence-based behaviour change interventions to improve
      retention in trials. METHODS: This research will generate data through semi
      structured interviews on stakeholders' perspectives of the reasons for trial non
      retention. It will identify perceived barriers and enablers to trial retention
      using the Theoretical Domains Framework. The intervention development work will
      involve identification of behaviour change techniques, using recognised
      methodology, and co-production of retention interventions through discussion
      groups with end-users. An evaluation of intervention acceptability and
      feasibility will be conducted in focus groups. Finally, a ready-to-use evaluation
      framework to deploy in Studies Within A Trial as well as an explanatory retention
      framework will be developed for identifying and tackling modifiable issues to
      improve trial retention. DISCUSSION: We believe this to be one of the first
      studies to apply a theoretical lens to the development of interventions to
      improve trial retention that have been informed by, and are embedded within,
      participants' experiential accounts. By developing and identifying priority
      interventions this study will support efforts to reduce research waste.

PMID- 29580261
TI  - A novel Babesia orientalis 135-kilodalton spherical body protein like:
      identification of its secretion into cytoplasm of infected erythrocytes.
AB  - BACKGROUND: The spherical body is a distinct organelle only existing in Babesia
      and Theileria. Spherical body proteins (SBPs) are secreted from spherical bodies
      and incorporated into the cytoplasm of infected erythrocytes during invasion and
      post-invasion stages. Four different SBP homologues (SBP1, SBP2, SBP3 and SBP4)
      have been identified in Babesia bovis and Babesia bigemina. So far, there has
      been no report available about the identification of SBPs in Babesia orientalis.
      METHODS: The SBP3-like in B. orientalis (BoSBP3-like) was cloned, sequenced,
      characterized and compared to the SBP3 sequences of B. bovis and B. bigemina by
      bioinformatics analyses. The BoSBP3-like gene was truncated into three fragments:
      BoSBP3-like-1 (915 bp), BoSBP3-like-2 (1311 bp) and BoSBP3-like-3 (1011 bp),
      which were amplified and cloned into the expression vector pET-28a and expressed
      as three truncated recombinant (His-fusion) proteins. The immunogenicity, native
      forms and localization of BoSBP3-like were identified by western blot and
      indirect immunofluorescence assay (IFA). RESULTS: The BoSBP3-like gene was
      intronless with an open reading frame (ORF) of 3237 bp, encoded a 1079 amino acid
      polypeptide with a predicted size of 135 kDa, and contained a cysteine-rich
      region, three dispersing FAINT domains and a signal peptide (1-16 aa) at the N
      terminus. The amino acid sequence of BoSBP3-like was 61.6 and 35.0% identical to
      that of B. bovis and B. bigemina, respectively. BoSBP3-like was identified as 135
      kDa in the parasite lysate by rabbit antiserum against the truncated recombinant
      BoSBP3-like-1 (rBoSBP3-like-1). Three specific bands corresponding to rBoSBP3
      like-1 (1-305 aa, 43 kDa), rBoSBP3-like-2 (306-742 aa, 58 kDa) and rBoSBP3-like-3
      (743-1079 aa, 52 kDa) were detected by reaction with serum from B. orientalis
      infected buffalo. The BoSBP3-like was not only localized in the spherical body of
      B. orientalis but also in the cytoplasm of infected erythrocytes of buffalo as
      puncta-like protein specks at both single and paired parasite development stages.
      CONCLUSIONS: Through secretion into the cytoplasm of infected erythrocytes,
      BoSBP3-like may play a significant role in adaptation, interaction, and
      modification related to the host environment to benefit the growth and survival
      of Babesia. BoSBP3-like could react with the serum from B. orientalis-infected
      buffalo, but not healthy buffalo, implicating that BoSBP3-like is highly
      antigenic and may serve as a candidate diagnostic antigen for the detection of B.
      orientalis.

PMID- 29580262
TI  - Treatment of B-cell precursor acute lymphoblastic leukemia with the Galectin-1
      inhibitor PTX008.
AB  - BACKGROUND: Drug resistance of B-cell precursor acute lymphoblastic leukemia (BP
      ALL) cells is conferred by both intrinsic and extrinsic factors, which could be
      targeted to promote chemo-sensitization. Our previous studies showed that
      Galectin-3, a lectin that clusters galactose-modified glycoproteins and that has
      both an intracellular and extracellular location, protects different subtypes of
      BP-ALL cells against chemotherapy. Galectin-1 is related to Galectin-3 and its
      expression was previously reported to be restricted to the MLL subtype of BP-ALL.
      METHODS AND RESULTS: Here, we report that Galectin-1 is expressed at different
      levels in and on different subclasses of BP-ALLs. Bone marrow plasma also
      contains high levels of Galectin-1. PTX008 is an allosteric inhibitor which
      inhibits Galectin-1 but not Galectin-3-mediated agglutination. The compound
      reduces migration of BP-ALL cells to CXCL12 and OP9 stromal cells and inhibits
      fibronectin-mediated adhesion. It also affects cell cycle progression of BCP-ALL
      cells. PTX008 is cytostatic for BP-ALL cells even when these are co-cultured with
      protective stroma, and can sensitize ALL cells to vincristine chemotherapy in
      vitro and in mice. CONCLUSIONS: PTX008 inhibits multiple functions that
      contribute to BP-ALL survival. The effects of Galectin-1 inhibition on both BP
      ALL cell proliferation and migration suggest both the leukemia cells as well as
      the microenvironment that protects these cells may be targeted.

PMID- 29580263
TI  - Post-millennial trends of socioeconomic inequalities in chronic illness among
      adults in Germany.
AB  - OBJECTIVE: Time trends in health inequalities have scarcely been studied in
      Germany as only few national data have been available. In this paper, we explore
      trends in socioeconomic inequalities in the prevalence of chronic illness using
      Germany-wide data from four cross-sectional health surveys conducted between 2003
      and 2012 (n = 54,197; ages 25-69 years). We thereby expand a prior analysis on
      post-millennial inequality trends in behavioural risk factors by turning the
      focus to chronic illness as the outcome measure. The regression-based slope index
      of inequality (SII) and relative index of inequality (RII) were calculated to
      estimate the extent of absolute and relative socioeconomic inequalities in
      chronic illness, respectively. RESULTS: The results for men revealed a
      significant increase in the extent of socioeconomic inequalities in chronic
      illness between 2003 and 2012 on both the absolute and relative scales (SII2003 =
      0.06, SII2012 = 0.17, p-trend = 0.013; RII2003 = 1.18, RII2012 = 1.57, p-trend =
      0.013). In women, similar increases in socioeconomic inequalities in chronic
      illness were found (SII2003 = 0.05, SII2012 = 0.14, p-trend = 0.022; RII2003 =
      1.14, RII2012 = 1.40, p-trend = 0.021). Whereas in men this trend was driven by
      an increasing prevalence of chronic illness in the low socioeconomic group, the
      trend in women was predominantly the result of a declining prevalence in the high
      socioeconomic group.

PMID- 29580264
TI  - Improving Recovery and Outcomes Every Day after the ICU (IMPROVE): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Delirium affects nearly 70% of older adults hospitalized in the
      intensive care unit (ICU), and many of those will be left with persistent
      cognitive impairment or dementia. There are no effective and scalable recovery
      models to remediate ICU-acquired cognitive impairment and its attendant elevated
      risk for dementia or Alzheimer disease (AD). The Improving Recovery and Outcomes
      Every Day after the ICU (IMPROVE) trial is an ongoing clinical trial which
      evaluates the efficacy of a combined physical exercise and cognitive training on
      cognitive function among ICU survivors 50 years and older who experienced
      delirium during an ICU stay. This article describes the study protocol for
      IMPROVE. METHODS: IMPROVE is a four-arm, randomized controlled trial. Subjects
      will be randomized to one of four arms: cognitive training and physical exercise;
      cognitive control and physical exercise; cognitive training and physical exercise
      control; and cognitive control and physical exercise control. Facilitators
      administer the physical exercise and exercise control interventions in individual
      and small group formats by using Internet-enabled videoconference. Cognitive
      training and control interventions are also facilitator led using Posit Science,
      Inc. online modules delivered in individual and small group format directly into
      the participants' homes. Subjects complete cognitive assessment, mood
      questionnaires, physical performance batteries, and quality of life scales at
      baseline, 3, and 6 months. Blood samples will also be taken at baseline and 3
      months to measure pro-inflammatory cytokines and acute-phase reactants;
      neurotrophic factors; and markers of glial dysfunction and astrocyte activation.
      DISCUSSION: This study is the first clinical trial to examine the efficacy of
      combined physical and cognitive exercise on cognitive function in older ICU
      survivors with delirium. The results will provide information about potential
      synergistic effects of a combined intervention on a range of outcomes and
      mechanisms of action. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03095417 .
      Registered on 23 March 2017. Last updated on 15 May 2017.

PMID- 29580265
TI  - Unexpected association between subclinical hearing loss and restorative sleep in
      a middle-aged and elderly Japanese population.
AB  - OBJECTIVE: Hearing loss may be associated with certain sleep abnormalities. We
      recently reported that subclinical hearing loss (SHL) was more prevalent in
      individuals in a broad Japanese population who slept longer than 8 h; however,
      the underlying mechanism was unknown. Therefore, we investigated the association
      between SHL and self-reported restorative sleep (RS), assessed by questionnaire,
      in a database of 33,888 Japanese aged 40-69 years without overt or diagnosed
      hearing loss (20,225 men, 13,663 women). RESULTS: The proportion of individuals
      with RS (more than half of the subjects) was significantly higher in the group
      with bilateral than with unilateral SHL at 4000 Hz and intact hearing; however,
      that was not the case at 1000 Hz, independent of age (P < 0.0001, two-way
      analysis of variance). Multivariate logistic regression analysis showed that
      bilateral SHL at 4000 Hz, but not at 1000 Hz, was significantly associated with
      RS. This relationship was independent of potential relevant confounders,
      including age, sex, and cardiometabolic risk factors. The present study extends
      our earlier work by revealing an unexpected association between early hearing
      impairment and satisfactory sleep in a middle-aged and elderly population. This
      association requires further confirmation regarding the possible underlying
      mechanism and clinical relevance.

PMID- 29580266
TI  - Synergistic anti-proliferative effects of combination of ABT-263 and MCL-1
      selective inhibitor A-1210477 on cervical cancer cell lines.
AB  - OBJECTIVE: There are number of studies which report that BCL-2 anti-apoptotic
      proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer
      tissues compared to the normal cervical epithelia. Despite these reports,
      targeting these proteins for cervical cancer treatment has not been explored
      extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may
      hold encouraging treatment outcomes for cervical cancer management. Hence, the
      aim of this pilot study is to investigate the sensitivity of cervical cancer cell
      lines to combination of two BH3-mimetics namely ABT-263 which selectively
      inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor.
      RESULTS: We report that combination of A-1210477 and ABT-263 exhibited
      synergistic effects on all cervical cancer cell lines tested. Drug sensitization
      studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa
      and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also
      occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A
      1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477
      could be a potential treatment strategy for cervical cancer. Extensive drug
      mechanistic studies and drug sensitivity studies in physiological models are
      necessary to unleash the prospect of this combination for cervical cancer
      therapy.

PMID- 29580267
TI  - Bevacizumab-induced intestinal perforation in a patient with inoperable breast
      cancer: a case report and review of the literature.
AB  - BACKGROUND: Gastrointestinal perforation is known as a serious adverse event,
      but, for breast cancer, there are very few reports of gastrointestinal
      perforation. This report highlights gastrointestinal perforation caused by
      bevacizumab for breast cancer, which is of special interest because
      gastrointestinal perforations caused by bevacizumab are very rare in breast
      cancer. CASE PRESENTATION: We describe the case of 54-year-old Japanese woman.
      She was diagnosed as having inoperable breast cancer T2 N1 M1 (pleura,
      peritoneum), Stage IV, and received chemotherapy by paclitaxel. There was
      reduction in the primary tumor and disappearance of the pleural effusion;
      however, the ascites did not change. We performed diagnostic laparoscopy which
      revealed that her whole peritoneum was thickened, and her small intestine, colon,
      and her omentum were grouped and formed an omental cake. We submitted a part of
      her peritoneum to pathological examination and diagnosed the peritoneum
      dissemination of breast cancer. On the basis of these results, paclitaxel and
      bevacizumab combination chemotherapy was started, and a decrease in ascites was
      seen. However, a gastrointestinal perforation occurred on 26th day of second
      cycle of bevacizumab + paclitaxel, and we performed an emergency operation. In
      the operation, the omental cake was resolved, and we could search the full length
      of the gastrointestinal tract. Two small perforations of her small intestine were
      seen. We performed simple closures for perforations, and peritoneal lavage and
      drainage. She was in a state of septic shock, but it improved. It was thought
      that the small intestinal perforations were caused by the bevacizumab-additional
      chemotherapy which was very effective. CONCLUSIONS: We report a very rare and
      valuable case. This case suggests that the risk of gastrointestinal perforation
      must be considered in a case of bevacizumab administration, and it is necessary
      to determine carefully the patient administered bevacizumab, regardless of the
      type of cancer.

PMID- 29580269
TI  - Comparison of an injectable toltrazuril-gleptoferron (Forceris(r)) and an oral
      toltrazuril (Baycox(r)) + injectable iron dextran for the control of
      experimentally induced piglet cystoisosporosis.
AB  - BACKGROUND: Cystoisospora suis causes diarrhoeal disease and reduced weight gain
      in suckling piglets, and a toltrazuril-based oral suspension is available for
      treatment. Recently a combinatorial product with toltrazuril plus iron has been
      developed for parenteral application. In this study we compared the efficacy of
      the injectable product with the oral suspension against experimentally induced
      piglet cystoisosporosis. METHODS: In a randomised controlled study, three groups
      of piglets (n = 10-13) were treated either with a fixed dose of 45 mg toltrazuril
      + 200 mg gleptoferron i.m. per piglet (Forceris(r)) on the second day of life
      (study day 2; SD 2) or with 20 mg toltrazuril/kg body weight as an oral
      suspension (Baycox(r) 5%) on SD 4 or left untreated (Control group). The
      Baycox(r) and the Control group received 200 mg of iron dextran/piglet on SD 2.
      All piglets were infected with 1000 sporulated C. suis oocysts on SD 3. Faecal
      samples were taken daily from SD 7 to SD 20 to determine faecal consistency,
      oocyst shedding and other diarrhoeal pathogens. Body weight was recorded on SD 1
      and then weekly until SD 29. Animals were observed daily for general health and
      after treatment for possible adverse events. RESULTS: In the Control group all
      animals shed oocysts for 3.1 days on average and all animals showed diarrhoea for
      an average of five days. Excretion peaked on SD 9 (max. 48,618 oocysts per gram
      of faeces). Treatment with Forceris(r) completely suppressed oocyst excretion. In
      the Baycox(r) group, low levels of excretion could be detected. Diarrhoea was
      reduced to single piglets in the treated groups. Body weight development was
      reduced in the Control group compared to the treated groups. Enteropathogenic
      bacteria (Escherichia coli, Clostridium perfringens) could be detected. All
      parameters related to oocyst excretion, faecal consistency and weight gain were
      significantly improved in the treated groups compared to the Control group
      without significant differences between the treated groups. Both products were
      safe to use. CONCLUSIONS: Treatment with both the injectable (Forceris(r)) and
      the oral (Baycox(r)) formulation of toltrazuril in the prepatent period were safe
      and highly effective against experimental infection with C. suis in newborn
      piglets.

PMID- 29580268
TI  - The impact of direct oral anticoagulants in traumatic brain injury patients
      greater than 60-years-old.
AB  - BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death among
      trauma patients. Patients under antithrombotic therapy (ATT) carry an increased
      risk for intracranial haematoma (ICH) formation. There is a paucity of data about
      the role of direct oral anticoagulants (DOACs) among TBI patients. METHODS: In
      this retrospective study, we investigated all TBI patients >=60-years-old who
      were admitted to the intensive care unit (ICU) from January 2014 until May 2017.
      Patients were grouped into those receiving vitamin K antagonists (VKA), platelet
      inhibitors (PI), DOACs and no antithrombotic therapy (no-ATT). RESULTS: One
      hundred-eighty-six, predominantly male (52.7%) TBI patients with a median age of
      79 years (range: 70-85 years) were enrolled in the study. Glasgow Coma Scale and
      S-100beta were not different among the groups. Patients on VKA and DOACs had a
      higher Charlson Comorbidity Index compared to the PI group and no-ATT group (p =
      0.0021). The VKA group received reversal agents significantly more often than the
      other groups (p < 0.0001). Haematoma progression in the follow-up cranial
      computed tomography (CCT) was lowest in the DOAC group. The number of CCT and
      surgical interventions were low with no differences between the groups. No
      relevant differences in ICU and hospital length of stay were observed. Mortality
      in the VKA group was significantly higher compared to DOAC, PI and no-ATT group
      (p = 0.047). DISCUSSION: Data from huge registry studies displayed higher
      efficacy and lower fatal bleeding rates for DOACs compared to VKAs. The current
      study revealed comparable results. Despite the fact that TBI patients on VKAs
      received reversal agents more often than patients on DOACs (84.4% vs. 24.2%, p <
      0.001), mortality rate was significantly higher in the VKA group (p = 0.047).
      CONCLUSION: In patients >=60 years suffering from TBI, anticoagulation with DOACs
      appears to be safer than with VKA. Anti-thrombotic therapy with VKA resulted in a
      worse outcome compared to DOACs and PI. Further studies are warranted to confirm
      this finding.

PMID- 29580270
TI  - Overactive bladder induces transient hypertension.
AB  - OBJECTIVES: Several studies have shown the relationship between lower urinary
      tract symptoms and autonomic imbalance. We investigated the relationship between
      detrusor overactivity (DO) or urgency, and transient increase in blood pressure
      as a type of hypertension related to sympathetic hyperactivity. Study 1: we
      enrolled 14 male patients with DO and 10 without DO. We measured the overactive
      bladder symptom score (OABSS) and blood pressure during cystometry. Study 2: we
      enrolled 14 men patients with overactive bladder (OAB) and 8 without OAB. We
      measured OABSS and blood pressure using a 24-h ambulatory device. RESULTS: Study
      1: the mean systolic pressure was significantly higher at urgency or SDV than at
      the other measurement points in the DO group (161.3 +/- 23.2 vs. 134.5 +/- 16.3,
      137.8 +/- 15.3, or 139.5 +/- 14.8 mmHg). Study 2: the mean systolic pressure was
      significantly higher at the measurement points before micturition than at the
      points unrelated to micturition in the OAB group (159.7 +/- 24.9 vs. 124.9 +/-
      13.8 mmHg). In conclusion, DO or urgency induces a transient increase of blood
      pressure, suggesting that OAB induces a type of hypertension before micturition.

PMID- 29580271
TI  - Local adaptation in European populations affected the genetics of psychiatric
      disorders and behavioral traits.
AB  - BACKGROUND: Recent studies have used genome-wide data to investigate evolutionary
      mechanisms related to behavioral phenotypes, identifying widespread signals of
      positive selection. Here, we conducted a genome-wide investigation to study
      whether the molecular mechanisms involved in these traits were affected by local
      adaptation. METHODS: We performed a polygenic risk score analysis in a sample of
      2455 individuals from 23 European populations with respect to variables related
      to geo-climate diversity, pathogen diversity, and language phonological
      complexity. The analysis was adjusted for the genetic diversity of European
      populations to ensure that the differences detected would reflect differences in
      environmental exposures. RESULTS: The top finding was related to the association
      between winter minimum temperature and schizophrenia. Additional significant geo
      climate results were also observed with respect to bipolar disorder (sunny
      daylight), depressive symptoms (precipitation rate), major depressive disorder
      (precipitation rate), and subjective well-being (relative humidity). Beyond geo
      climate variables, we also observed findings related to pathogen diversity and
      language phonological complexity: openness to experience was associated with
      protozoan diversity; conscientiousness and extraversion were associated with
      language consonants. CONCLUSIONS: We report that common variation associated with
      psychiatric disorders and behavioral traits was affected by processes related to
      local adaptation in European populations.

PMID- 29580272
TI  - Ejaculated boar spermatozoa displaying a rare multivesicular defect.
AB  - Two cases of a previously unreported sperm defect appearing in boar studs in
      Finland are presented. Spermatozoa showed small particles scattered on their
      surface with a prevalence decreasing with boar age. Semen samples, either stained
      with eosin-nigrosin or examined with phase contrast optics on formaldehyde-fixed
      spermatozoa, revealed the presence of multiple particles attached to the surface
      of spermatozoa counted as dead cells at fixation. Transmission electron
      microscopy revealed these were multivesicular and multilamellar vesicles, built
      up by phospholipid membranes. The case is classified as a post-epididymal
      multivesicular sperm defect with a favorable prognosis.

PMID- 29580273
TI  - Effect of total exemption from medical service co-payments on potentially
      inappropriate medication use among elderly ambulatory patients in a single center
      in Japan: a retrospective cross-sectional study.
AB  - OBJECTIVE: The effect of total exemption from medical service co-payments on drug
      prescribing practices has not been extensively evaluated. We conducted a
      retrospective cross-sectional study to evaluate the effect of total exemption
      from medical service co-payments on potentially inappropriate medication (PIM)
      and benzodiazepine use in elderly ambulatory patients. We defined PIM based on
      the Beers Criteria. RESULTS: Six hundred seventy-one consecutive patients aged 65
      years or older who routinely visited internal medicine physicians were included.
      Their mean age was 75.7 years, and 342 (51.0%) patients were men. The proportions
      of patients taking any PIMs or benzodiazepines were 37.7% and 16.2%,
      respectively. Of all patients, 62 (9.2%) were totally exempt from medical service
      co-payments. The patients who were totally exempt from medical service co
      payments showed a significantly increased risk of PIM (OR 2.16, 95% CI 1.28-3.66)
      or benzodiazepine use (OR 2.12, 95% CI 1.16-3.87) compared with patients who were
      not. These associations did not change after adjusting for age, gender,
      comorbidities and polypharmacy. These findings should be confirmed in other
      settings or hospitals in Japan.

PMID- 29580274
TI  - Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and
      lymphocytes in patients with anterior tuberculosis compared to tobacco related
      COPD.
AB  - OBJECTIVE: The inflammatory profile of chronic obstructive pulmonary disease
      (COPD) related to tobacco is known in certain studies while that of the post
      tuberculosis form is not yet known. This study aimed to evaluate the levels of
      neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with
      history of smoking or anterior tuberculosis. Enumeration of cells in samples was
      analyzed using standard microscopy. RESULTS: We enrolled 92 participants, 46
      (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with
      anterior tuberculosis while 46 (50%) healthy persons constituted the control
      group. The levels of neutrophils, lymphocytes and monocytes were statistically
      higher in COPD patients compared to the control group with p-values of 0.0001
      respectively. Neutrophils levels were higher in COPD patients with history of
      tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72
      * 106/ml and 2.48 * 106/ml respectively (p = 0.04). The monocytes and lymphocytes
      levels were not statistically different between the two sub-groups of COPD
      patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only
      inflammatory cells that were significantly higher in COPD patients with history
      of smoking as compared to COPD patients with anterior tuberculosis.

PMID- 29580275
TI  - The emerging roles of exosomes in the modulation of immune responses in cancer.
AB  - Exosomes are promising tools for improving cancer care, but conversely may also
      contribute to tumor progression. Here, we highlight recently discovered roles of
      exosomes in modulating immune responses in cancer, with emphasis on exosomal
      surface proteins and on RNA and DNA content. We also discuss how exosomes could
      be exploited as biomarkers and delivery vehicles in cancer therapy.

PMID- 29580276
TI  - Indicators for prediction of Mycobacterium tuberculosis positivity detected with
      bronchoalveolar lavage fluid.
AB  - BACKGROUND: The diagnosis of active pulmonary tuberculosis (TB) remains a
      challenge in clinic, especially for sputum negative pulmonary TB. Bronchoalveolar
      lavage fluid (BALF) has higher sensitivity than sputum for detection of
      Mycobacterium tuberculosis (Mtb). However, bronchoscopy is invasive and costly,
      and not suitable for all patients. In order to make TB patients get more benefit
      from BALF for diagnosis, we explore which indicator might be used to optimize the
      choice of bronchoscopy. METHODS: A total of 1539 sputum-smear-negative pulmonary
      TB suspects who underwent bronchoscopy were recruited for evaluation. The
      sensitivity, specificity and accuracy of Mtb detection in sputum and BALF were
      compared. Odds ratios and 95% confidence intervals were used to assess variables
      that associated with positive acid-fast bacilli (AFB) smear, Mtb culture and
      nucleic acid amplification test (NAAT) of BALF in sputum-negative and non-sputum
      producing pulmonary TB suspects. RESULTS: BALF has significantly higher
      sensitivity (63.4%) than sputum (43.5%) for Mtb detection by culture and NAAT.
      19.7% (122/620) sputum-negative and 40.0% (163/408) non-sputum-producing suspects
      had positive bacteriological results in BALF. Among sputum-negative and non
      sputum-producing pulmonary TB suspects, the positivity of Mtb detection in BALF
      is associated with a younger age, the presence of pulmonary cavities and a
      positive result of interferon-gamma release assay (IGRA). Sputum-negative
      patients under 35 years old with positive IGRA and pulmonary cavity had 84.8%
      positivity of Mtb in BALF. CONCLUSIONS: Our study indicated that combination of
      age, the presence of pulmonary cavity, and the result of IGRA is useful to
      predict the positivity of Mtb detection in BALF among sputum-negative and non
      sputum producing pulmonary TB suspects. Those who are under 35 years old,
      positive for the presence of pulmonary cavity and IGRA, should undergo
      bronchoscopy to collect BAFL for Mtb tests, as they have the highest possibility
      to get bacteriologically confirmation of TB.

PMID- 29580277
TI  - How to best distribute written patient education materials among patients with
      rheumatoid arthritis: a randomized comparison of two strategies.
AB  - BACKGROUND: The aim of this randomized controlled trial was to evaluate the
      effect of a 'supply on demand'-distribution strategy, compared to an 'unsolicited
      supply'-distribution strategy, on the use of a care booklet and clinical outcomes
      among patients with rheumatoid arthritis (RA). In addition, differences in socio
      demographic and clinical characteristics between users and non-users were
      explored. METHODS: As part of regular care the care booklet was distributed among
      RA-patients of two hospitals in the Netherlands. 1000 patients received the care
      booklet by mail, whereas another 1000 received an information letter with the
      option to order the care booklet. Four months after distribution, a random sample
      of 810 patients (stratified by hospital and distribution method) received a
      questionnaire on the use of the booklet, social-demographic and clinical
      characteristics. To compare effects between the two distribution strategies and
      differences between users and non-users univariate and multilevel regression
      analyses were performed. Secondary analysis included a per-protocol analysis
      (excluding participants who did not order the care booklet). RESULTS: One hundred
      ninety four patients in the 'unsolicited supply' and 176 patients in the 'supply
      on demand' group (46%) returned the questionnaire. In the 'supply on demand'
      group 106 (60.2%) participants ordered the care booklet. In total, no difference
      was found in use between the 'unsolicited supply'-group (23.2%) and the 'supply
      on demand'-group (21.6%) (OR 0.9 CI:0.6-1.5). However, the proportion of users
      among patients in the 'supply on demand'-group who ordered the booklet (35%) was
      significantly higher than in the 'unsolicited supply'-group (OR 1.9 CI:1.1-3.2).
      Regardless of distribution method, use of the care booklet was associated with
      being married (OR 2.4 CI:1.2-4.6), higher disease activity (mean difference 0.5
      CI: 0.0-1.1), more activity limitations (mean difference 0.2 CI: 0.1-0.4), use of
      corticosteroids (OR 1.9 CI:1.0-3.5), perception of disease course as fluctuating
      (mean difference 1.4 CI:0.5-2.3) and higher educational needs (mean difference
      9.7 CI: 2.9-16.6). CONCLUSIONS: From an economic and environmental perspective a
      'supply on demand'-distribution strategy could be recommended. Results of this
      study provide starting points to optimize further implementation strategies of a
      care-booklet in routine care. TRIAL REGISTRATION: ISRCTN registry (
      ISRCTN22703067 ). Retrospectively registered 27 March 2017.

PMID- 29580278
TI  - A mobile phone based tool to identify symptoms of common childhood diseases in
      Ghana: development and evaluation of the integrated clinical algorithm in a cross
      sectional study.
AB  - BACKGROUND: The aim of this study was the development and evaluation of an
      algorithm-based diagnosis-tool, applicable on mobile phones, to support guardians
      in providing appropriate care to sick children. METHODS: The algorithm was
      developed on the basis of the Integrated Management of Childhood Illness (IMCI)
      guidelines and evaluated at a hospital in Ghana. Two hundred and thirty-seven
      guardians applied the tool to assess their child's symptoms. Data recorded by the
      tool and health records completed by a physician were compared in terms of
      symptom detection, disease assessment and treatment recommendation. To compare
      both assessments, Kappa statistics and predictive values were calculated.
      RESULTS: The tool detected the symptoms of cough, fever, diarrhoea and vomiting
      with good agreement to the physicians' findings (kappa = 0.64; 0.59; 0.57 and
      0.42 respectively). The disease assessment barely coincided with the physicians'
      findings. The tool's treatment recommendation correlated with the physicians'
      assessments in 93 out of 237 cases (39.2% agreement, kappa = 0.11), but
      underestimated a child's condition in only seven cases (3.0%). CONCLUSIONS: The
      algorithm-based tool achieved reliable symptom detection and treatment
      recommendations were administered conformably to the physicians' assessment.
      Testing in domestic environment is envisaged.

PMID- 29580279
TI  - Distinct clinical characteristics and helminth co-infections in adult
      tuberculosis patients from urban compared to rural Tanzania.
AB  - BACKGROUND: Differences in rural and urban settings could account for distinct
      characteristics in the epidemiology of tuberculosis (TB). We comparatively
      studied epidemiological features of TB and helminth co-infections in adult
      patients from rural and urban settings of Tanzania. METHODS: Adult patients (>=
      18 years) with microbiologically confirmed pulmonary TB were consecutively
      enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants
      (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000
      inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine
      samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine
      filtration, and circulating cathodic antigen tests. Differences between groups
      were assessed by chi2, Fisher's exact, and Wilcoxon rank sum tests. Logistic
      regression models were used to determine associations. RESULTS: Between August
      2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and
      208 (31.1%) at the rural site. Median patient age was 35 years (interquartile
      range [IQR]: 27-41.5 years), and 454 (68%) were males. Patients from the rural
      setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower
      median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P <  0.001), a higher
      proportion of recurrent TB cases (9% vs. 1%, P <  0.001), and in HIV/TB co
      infected patients a lower median CD4 cell counts (147 cells/MUl vs. 249
      cells/MUl, P = 0.02) compared to those from urban Tanzania. There was no
      significant difference in frequencies of HIV infection, diabetes mellitus, and
      haemoglobin concentration levels between the two settings. The overall prevalence
      of helminth co-infections was 22.9% (95% confidence interval [CI]: 20.4-27.0%).
      The significantly higher prevalence of helminth infections at the urban site
      (25.7% vs. 17.3%, P = 0.018) was predominantly driven by Strongyloides
      stercoralis (17.0% vs. 4.8%, P <  0.001) and Schistosoma mansoni infection (4.1%
      vs. 16.4%, P <  0.001). Recurrent TB was associated with living in a rural
      setting (adjusted odds ratio [aOR]: 3.97, 95% CI: 1.16-13.67) and increasing age
      (aOR: 1.06, 95% CI: 1.02-1.10). CONCLUSIONS: Clinical characteristics and
      helminth co-infections pattern differ in TB patients in urban and rural Tanzania.
      The differences underline the need for setting-specific, tailored public health
      interventions to improve clinical management of TB and comorbidities.

PMID- 29580280
TI  - Report of the first international workshop on onchocerciasis-associated epilepsy.
AB  - BACKGROUND: Recently, several epidemiological studies performed in Onchocerca
      volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy
      (OAE) may constitute an important but neglected public health problem in many
      countries where onchocerciasis is still endemic. MAIN TEXT: On October 12-14th
      2017, the first international workshop on onchocerciasis-associated epilepsy
      (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants
      from 20 different countries. Recent research findings strongly suggest that O.
      volvulus is an important contributor to epilepsy, particularly in meso- and
      hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated
      with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures
      but also atonic neck seizures (nodding), and stunted growth. OAE is characterised
      by an onset of seizures between the ages of 3-18 years. Multidisciplinary working
      groups discussed topics such as how to 1) strengthen the evidence for an
      association between onchocerciasis and epilepsy, 2) determine the burden of
      disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons
      with OAE and affected families, 5) identify the pathophysiological mechanism of
      OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence
      associated with OAE. An OAE Alliance was created to increase awareness about OAE
      and its public health importance, stimulate research and disseminate research
      findings, and create partnerships between OAE researchers, communities, advocacy
      groups, ministries of health, non-governmental organisations, the pharmaceutical
      industry and funding organizations. CONCLUSIONS: Although the exact
      pathophysiological mechanism underlying OAE remains unknown, there is increasing
      evidence that by controlling and eliminating onchocerciasis, OAE will also
      disappear. Therefore, OAE constitutes an additional argument for strengthening
      onchocerciasis elimination efforts. Given the high numbers of people with
      epilepsy in O. volvulus-endemic regions, more advocacy is urgently needed to
      provide anti-epileptic treatment to improve the quality of life of these
      individuals and their families.

PMID- 29580281
TI  - A retrospective review of 146 active and passive fixation bradycardia lead
      implantations in 74 dogs undergoing pacemaker implantation in a research setting
      of short term duration.
AB  - BACKGROUND: Canine veterinary patients increasingly benefit from implantation of
      transvenous pacemakers for bradyarrhythmias. No published data exist examining
      procedural outcomes of pacemaker implantation performed in the preclinical
      laboratory. The purpose was to review short term complication, infection,
      dislodgement, penetration rates, plus overall morbidity following pacemaker
      implantation in the research setting. A retrospective review of 74 Class A
      purpose-bred mongrels implanted with active (n = 89) and passive fixation (n =
      57) intracardiac leads for dual (n = 72) or single (n = 2) chamber pacing was
      performed. RESULTS: All leads were implanted successfully, meeting electrical
      implant criteria. Follow-ups typically occurred every 7 days (first month), then
      at 30 day intervals. Seroma formation was 1.4% and 10.8% at the venotomy and
      pulse generator site respectively. Overall infection rate was 1.4%. Overall
      dislodgement rate was 2.1%, (2 passive atrial leads, 1 passive ventricular lead).
      Overall fractures and insulation defects were zero. Two helix penetrations were
      noted incidentally post mortem, one at the right atrial appendage and one at the
      right ventricle (64 dogs, 128 leads evaluated), a 1.6% event rate. Major in-life
      adverse events were 5.4% (4 of 74 dogs), including 1 infection and 3 lead
      dislodgements. CONCLUSIONS: This review demonstrates a low complication rate with
      bradycardia lead implants in the short term (up to 180 days), in a high volume
      research setting. Lead type, implant technique, surgeon experience, healthy
      patient population, patient size and follow-up care play a role. This review also
      suggests active fixation leads in the right atrial appendage of dogs are safe and
      reliable.

PMID- 29580282
TI  - Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD.
AB  - BACKGROUND: Asthma-chronic obstructive pulmonary disorder (COPD) overlap (ACO) is
      characterized by the coexistence of features of both asthma and COPD and is
      associated with rapid progress and a poor prognosis. Thus, the early recognition
      of ACO is crucial. OBJECTIVES: We sought to explore the plasma levels of
      biomarkers associated with asthma (periostin, TSLP and YKL-40), COPD (NGAL) and
      their possible correlation with lung function, the bronchodilator response and
      radiographic imaging in patients with asthma, COPD and with features of ACO.
      METHODS: We enrolled 423 subjects from 6 clinical centers. All participants
      underwent blood collection, lung function measurements, bronchodilator response
      tests and high-resolution CT. Correlations of the plasma biomarkers with lung
      function, the bronchodilator response and percentemphysema were calculated by
      Spearman's rank correlation and multivariate stepwise regressionanalysis.
      RESULTS: 1) Patients with features of ACO had lower plasma YKL-40 than COPD
      patients and a moderate elevated plasma level of NGAL compared with asthma
      patients. 2) Patients with features of ACO had an intermediate degree of airflow
      obstruction, the bronchodilator response and emphysema between patients with COPD
      and asthma. 3) Plasma YKL-40 was negatively correlated with lung function and
      with the bronchodilator response, and plasma NGAL was positively correlated with
      the extent of emphysema. CONCLUSIONS: Plasma YKL-40 is a promising candidate for
      distinguishing between patients with features of ACO and COPD patients, while
      plasma NGAL may be a valuable biomarker for differentiating between patients with
      features of ACO and asthma patients. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC
      16009221.

PMID- 29580283
TI  - Prevalence and reasons for intentional use of complementary and alternative
      medicine as an adjunct to future visits to a medical doctor for chronic disease.
AB  - BACKGROUND: Intentional use of complementary and alternative medicine (CAM) has
      previously only been researched in small, possibly biased, samples. There seems
      to be a lack of scientific information regarding healthy individual's attitudes
      and presumed use of CAM. The aim of this study is to describe prevalence and
      characteristics of participants who intend to see a CAM provider compared to
      participants who intend to see a medical doctor (MD) only when suffering from a
      chronic, non- life-threatening disease and in the need of treatment. Further to
      describe differences between the groups regarding expected reasons for CAM use
      and expected skills of CAM providers. METHOD: The survey was conducted in January
      2016 as part of the "TNS Gallup Health policy Barometer". In total, 1728
      individuals aged 16-92 years participated in the study, constituting an overall
      response rate of 47%. The survey included questions regarding opinions and
      attitudes towards health, health services and health politics in Norway. RESULTS:
      The majority of the participants (90.2%) would see a MD only if they were
      suffering from a chronic, non- life-threatening disease and were in the need of
      treatment. Men over the age of 60 with a university education tended to see a MD
      only. Only 9.8% of all respondents would in addition visit a CAM provider. Being
      an intentional user of a MD + CAM provider was associated with being a woman
      under the age of 60. The respondents believed that CAM providers have
      professional competence based on formal training in CAM. They also believed that
      individuals seeing a CAM provider have poor health and are driven by the hope of
      being cured. Further, that they have heard that others have good experience with
      such treatment. CONCLUSION: Intentional use of CAM is associated with positive
      attitudes, trustworthiness, and presumed positive experiences in the CAM-patient
      setting. Intentional CAM users also have the impression that CAM providers have
      professional competence based on formal training in alternative therapies.

PMID- 29580284
TI  - The development of facility standards for common outpatient procedures and
      implications for the context of abortion.
AB  - BACKGROUND: In recent years, an increasing number of states have enacted laws
      that impose specific requirements for facilities in which abortions are
      performed. In this study, we sought to understand the processes used to develop
      facility standards in the context of other, less politically charged areas of
      health care and consider implications for the context of abortion. METHODS: We
      conducted key informant interviews with 20 clinicians and accreditation
      professionals involved in facility standards development for common outpatient
      procedures (endoscopy, gynecology, oral surgery, plastic surgery). We examined
      the motivations for and processes used in facility standards development, use of
      scientific evidence in standards development, and decision-making in the absence
      of evidence. Interview data were thematically coded and analyzed using an
      iterative approach. RESULTS: In contrast to U.S. state laws that target abortion
      facilities, standards for other outpatient procedures are commonly set by
      committees of clinicians organized by professional associations or accreditation
      organizations. These committees seek to establish standards that ensure patient
      safety without placing unnecessary burden on clinicians in practice. They aim to
      create evidence-based standards but can be hampered by lack of relevant research.
      In the absence of research evidence, committees rely on their clinical expertise
      and sense of best practices in decision-making. According to respondents,
      considerations of potential harm (e.g., deeper levels of sedation, invasiveness),
      rather than the specific procedure, should prompt additional requirements.
      CONCLUSIONS: If facility standards in the context of abortion were developed
      through processes similar to other outpatient procedures, 1) professionals who
      perform the procedure would be involved in standards development and 2) in the
      absence of clear research evidence, the expertise of clinicians, and the
      guidelines and standards of other organizations, are used to describe a best
      practice standard of care.

PMID- 29580285
TI  - Pioglitazone is effective for multiple phenotyepes of the Zucker fa/fa rat with
      polycystc ovary morphology and insulin resistance.
AB  - BACKGROUND: Hyperandrogenism and insulin resistance may be related to the
      etiology of PCOS. Zucker fa/fa rats with polycystic ovary are obese, have insulin
      resistance without diabetes mellitus or hyperandrogenism and can be utilized as
      PCOS model rats without effects of hyperandrogenemia. PCOS patients are reported
      to have elevated levels of serum anti-Mullerian hormone (AMH), which has an
      inhibitory action on folliculogenesis, and low levels of serum adiponectin, which
      blocks apoptosis and induces biological effects in some tissues. Pioglitazone, an
      insulin sensitizer, is administered to PCOS patients with insulin resistance to
      induce ovulation but the mechanisms by which this occurs have not been
      elucidated. METHODS: We purchased 4-week-old female fatty Zucker fa/fa rats as
      well as lean Zucker +/+ rats for use as control rats with normal insulin
      sensitivity. The Zucker fa/fa rats were administered pioglitazone (2.5 mg/kg body
      weight/day) or a vehicle every day for 14 days in separate groups. The Zucker +/+
      rats were also administered the vehicle. After 2 weeks of treatment, they were
      euthanized and we obtained serum samples and both ovaries and determined the body
      weight, ovarian weight, and serum AMH, adiponectin, testosterone, and
      androstenedione levels. We also examined ovarian histology to check follicle
      numbers by using hematoxylin-eosin staining, and the number of atretic follicles
      using Tdt-mediated dUTP nick end labeling (TUNEL) methods. RESULTS: The Zucker
      fa/fa rats used as PCO model rats and Pioglitazone treated PCO model rats were
      significantly heavier than the Zucker +/+ control rats (p < 0.05) at 15 day old.
      Pioglitazone treatment did not influence body weight or ovarian weight in either
      group. However, the total number of follicles was significantly larger in the PCO
      model rats than in the control rats (P < 0.05). Although pioglitazone treatment
      appeared to decrease the total number of follicles in the PCO model rats, the
      decrease was not statistically significant. However, pioglitazone treatment
      significantly decreased the total number of atretic follicles and the rate of
      atreteic follicles in the PCO model rats (P < 0.05). The serum AMH level was
      significantly higher in the PCO model rats than in the control rats. Pioglitazone
      treatment significantly decreased the serum AMH level and significantly increased
      the serum adiponectin level in the PCO model rats (P < 0.05). Serum testosterone
      and androstenedione levels were quite low or undetectable in the 3 groups of
      rats, and were not influenced by pioglitazone treatment. CONCLUSION: In this
      study, pioglitazone treatment reduced the serum AMH level and increased the serum
      adiponectin level in PCO model rats. These effects are related to reduction of
      the total number of atretic follicles and rate of atretic follicles. This proves
      that pioglitazone treatment improves healthy follicle growth in these PCO model
      rats with insulin resistance.

PMID- 29580286
TI  - Hematoma block or procedural sedation and analgesia, which is the most effective
      method of anesthesia in reduction of displaced distal radius fracture?
AB  - BACKGROUND: Procedure sedation and analgesia (PSA) is often used to alleviate
      discomfort and to facilitate fracture reduction for patients with distal radius
      fracture in emergency departments and clinics, but risks of respiratory distress
      and needs for different levels of monitoring under PSA are still under concern.
      Hematoma block (HB) is a simple alternative method of providing rapid pain relief
      during reduction of distal radius fracture. However, there is still in lack of
      strong evidence to promote HB over PSA in clinical practice. The aim of this
      study was to compare HB and PSA for adult and pediatric patients during reduction
      of displaced distal radius fracture to identify the level of pain relief,
      frequency of adverse effects (AEs), and reduction failure. METHODS: The PubMed,
      ScienceDirect, Cochrane Library, and ClinicalTrials.gov were searched for studies
      comparing HB or PSA in distal radius fracture reduction. The search revealed four
      randomized controlled trials and one non-randomized trial, which included two
      studies of pediatric subjects and three studies of adult subjects. Subgroup meta
      analysis for adult and pediatric groups were specifically performed according to
      age difference to avoid potential bias. RESULTS: In the adult group, the effect
      of HB on post-reduction pain severity was better than that of PSA with
      significant heterogeneity (Hedges' g - 0.600, 95% confidence interval (CI) -
      1.170 to - 0.029, p = 0.039), although there was no difference on the pain
      severity during reduction between these two groups with significant heterogeneity
      (Hedges' g 0.356, 95% CI - 1.101 to 1.812, p = 0.632). In the pediatric group,
      the treatment effect on pain severity was significantly better by HB than that by
      PSA but without significant heterogeneity (Hedges' g - 0.402, 95% CI - 0.718 to -
      0.085, p = 0.013, I 2  < 0.001%). Most of the reported adverse effects (AEs)
      include nausea, vomiting, and respiratory distress developed in adult patients
      treated by PSA. The rates of reported AEs did not significantly differ between HB
      and PSA in the pediatric group. Additionally, final outcomes of reduction failure
      did not significantly differ between HB and PSA in both adult and pediatric
      groups. CONCLUSION: Hematoma block is a safe and effective alternative of
      anesthesia in reduction of distal radius fracture without inferior pain relief
      compared with PSA among adult and pediatric patients.

PMID- 29580287
TI  - How I do it: feasibility of a new ultrasound probe fixator to facilitate high
      quality stress echocardiography.
AB  - BACKGROUND: Stress echocardiography (SE) has recently regained momentum as an
      important diagnostic tool for the assessment of both ischemic and non-ischemic
      heart disease. Performing SE during physical exercise is challenging due to a
      suboptimal patient position and vigorous movements of the patient's chest. This
      hampers a stable ultrasound position and reduces the diagnostic performance of
      SE. A stable ultrasound probe position would facilitate producing high quality
      images during continuous measurements. With Probefix (Usono, Eindhoven, The
      Netherlands), a newly developed tool to fixate the ultrasound probe to the
      patient's chest, stabilization of the probe during physical exercise is possible.
      IMPLEMENTATION AND RESULTS: The technique of SE with the Probefix and its'
      feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound
      probe to the patient's chest, using two chest straps and a fixation device. The
      ultrasound probe position and angle may be altered with a relative high degree of
      freedom. We tested the Probefix for continuous echocardiographic imaging in 12
      study subjects during supine and upright ergometer stress tests. One patient was
      unable to perform exercise and in two study subjects good quality images were not
      achieved. In the other patients (82%) a stable probe position was obtained, with
      subsequent good quality echocardiographic images during SE. CONCLUSION: We have
      demonstrated the feasibility of the Probefix support during ergometer tests in
      supine and upright positions and conclude that this external fixator may
      facilitate continuous monitoring of cardiac function in a group of patients.

PMID- 29580288
TI  - Modulating PD-L1 expression in multiple myeloma: an alternative strategy to
      target the PD-1/PD-L1 pathway.
AB  - Even with recent advances in therapy regimen, multiple myeloma patients commonly
      develop drug resistance and relapse. The relevance of targeting the PD-1/PD-L1
      axis has been demonstrated in pre-clinical models. Monotherapy with PD-1
      inhibitors produced disappointing results, but combinations with other drugs used
      in the treatment of multiple myeloma seemed promising, and clinical trials are
      ongoing. However, there have recently been concerns about the safety of PD-1 and
      PD-L1 inhibitors combined with immunomodulators in the treatment of multiple
      myeloma, and several trials have been suspended. There is therefore a need for
      alternative combinations of drugs or different approaches to target this pathway.
      Protein expression of PD-L1 on cancer cells, including in multiple myeloma, has
      been associated with intrinsic aggressive features independent of immune evasion
      mechanisms, thereby providing a rationale for the adoption of new strategies
      directly targeting PD-L1 protein expression. Drugs modulating the transcriptional
      and post-transcriptional regulation of PD-L1 could represent new therapeutic
      strategies for the treatment of multiple myeloma, help potentiate the action of
      other drugs or be combined to PD-1/PD-L1 inhibitors in order to avoid the
      potentially problematic combination with immunomodulators. This review will focus
      on the pathophysiology of PD-L1 expression in multiple myeloma and drugs that
      have been shown to modulate this expression.

PMID- 29580289
TI  - A multi-host approach to identify a transposon mutant of Pseudomonas aeruginosa
      LESB58 lacking full virulence.
AB  - OBJECTIVE: Pseudomonas aeruginosa is an opportunistic bacterial pathogen well
      known to cause chronic lung infections in individuals with cystic fibrosis (CF).
      Some strains adapted to this particular niche show distinct phenotypes, such as
      biofilm hyperproduction. It is necessary to study CF clinical P. aeruginosa
      isolates, such as Liverpool Epidemic Strains (LES), to acquire a better
      understanding of the key genes essential for in vivo maintenance and the major
      virulence mechanisms involved in CF lung infections. Previously, a library of
      9216 mutants of the LESB58 strain were generated by signature-tagged mutagenesis
      (STM) and screened in the rat model of chronic lung infection, allowing the
      identification of 163 STM mutants showing defects in in vivo maintenance.
      RESULTS: In the present study, these 163 mutants were successively screened in
      two additional surrogate host models (the amoeba and the fruit fly). The STM
      PALES_11731 mutant was the unique non-virulent in the three hosts. A competitive
      index study in rat lungs confirmed that the mutant was 20-fold less virulent than
      the wild-type strain. This study demonstrated the pertinence to use a multi-host
      approach to study the genetic determinants of P. aeruginosa strains infecting CF
      patients.

PMID- 29580290
TI  - Rescue of an aggressive female sexual courtship in mice by CRISPR/Cas9 secondary
      mutation in vivo.
AB  - OBJECTIVE: We had previously reported a mouse line carrying the Atypical female
      courtship (HoxD Afc ) allele, where an ectopic accumulation of Hoxd10 transcripts
      was observed in a sparse population of cells in the adult isocortex, as a result
      of a partial deletion of the HoxD gene cluster. Female mice carrying this allele
      displayed an exacerbated paracopulatory behavior, culminating in a severe
      mutilation of the studs' external genitals. To unequivocally demonstrate that
      this intriguing phenotype was indeed caused by an illegitimate function of the
      HOXD10 protein, we use CRISPR/Cas9 technology to induce a microdeletion into the
      homeobox of the Hoxd10 gene in cis with the HoxD Afc allele. RESULTS: Females
      carrying this novel HoxDDel(1-9)d10hd allele no longer mutilate males. We
      conclude that a brain malfunction leading to a severe pathological behavior can
      be caused by the mere binding to DNA of a transcription factor expressed
      ectopically. We also show that in HoxD Afc mice, Hoxd10 was expressed in cells
      containing glutamate decarboxylase (Gad1) and Cholecystokinin (Cck) transcripts,
      corroborating our proposal that a small fraction of GABAergic neurons in adult
      hippocampus may participate to some aspects of female courtship.

PMID- 29580291
TI  - Pulling the genome in opposite directions to dissect gene networks.
AB  - Orthogonal CRISPR-Cas systems have been integrated into combinatorial screens to
      decipher complex genetic relationships in two recent studies.

PMID- 29580292
TI  - Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in
      childhood.
AB  - BACKGROUND: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder
      with oculocutaneous albinism, may be caused by mutations in one of at least 10
      separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia
      and knowledge of its pulmonary phenotype in children is scarce. METHODS: Six
      children with genetically proven HPS-2 presented to the chILD-EU register between
      2009 and 2017; the data were collected systematically and imaging studies were
      scored blinded. RESULTS: Pulmonary symptoms including dyspnea, coughing, need for
      oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean
      age of 8.83 years (range 2-15). All children had recurrent pulmonary infections,
      3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of
      pulmonary complaints increased over time. The leading radiographic pattern was
      ground-glass opacities with a rapid increase in reticular pattern and traction
      bronchiectasis between initial and follow-up Computer tomography (CT) in all
      subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the
      patients received a lung biopsy for diagnosis; histological patterns were
      cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like,
      and desquamative interstitial pneumonia. CONCLUSIONS: HPS-2 is characterized by a
      rapidly fibrosing lung disease during early childhood. Effective treatments are
      required.

PMID- 29580293
TI  - Effects of oncological care pathways in primary and secondary care on patient,
      professional, and health systems outcomes: protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: The high impact of a cancer diagnosis on patients and their families
      and the increasing costs of cancer treatment call for optimal and efficient
      oncological care. To improve the quality of care and to minimize healthcare costs
      and its economic burden, many healthcare organizations introduce care pathways to
      improve efficiency across the continuum of cancer care. However, there is limited
      research on the effects of cancer care pathways in different settings. METHODS:
      The aim of this systematic review and meta-analysis described in this protocol is
      to synthesize existing literature on the effects of oncological care pathways. We
      will conduct a systematic search strategy to identify all relevant literature in
      several biomedical databases, including Cochrane library, MEDLINE, Embase, and
      CINAHL. We will follow the methodology of Cochrane Effective Practice and
      Organisation of Care (EPOC), and we will include randomized trials, non
      randomized trials, controlled before-after studies, and interrupted time series
      studies. In addition, we will include full economic evaluations (cost
      effectiveness analyses, cost-utility analyses, and cost-benefit analyses), cost
      analyses, and comparative resource utilization studies, if available. Two
      reviewers will independently screen all studies and evaluate those included for
      risk of bias. From these studies, we will extract data regarding patient,
      professional, and health systems outcomes. Our systematic review will follow the
      PRISMA set of items for reporting in systematic reviews and meta-analyses.
      DISCUSSION: Following the protocol outlined in this article, we aim to identify,
      assess, and synthesize all available evidence in order to provide an evidence
      base on the effects of oncological care pathways as reported in the literature.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017057592 .

PMID- 29580294
TI  - First report of Giardia duodenalis and Enterocytozoon bieneusi in forest musk
      deer (Moschus berezovskii) in China.
AB  - BACKGROUND: Giardia duodenalis and Enterocytozoon bieneusi are widespread
      pathogens that can infect humans and various animal species. Thus far, there are
      only a few reports of G. duodenalis and E. bieneusi infections in ruminant
      wildlife. Thus, the objective of this study was to examine the prevalence of G.
      duodenalis and E. bieneusi in forest musk deer in Sichuan, China, as well as
      identifying their genotypes. RESULTS: In total, we collected 223 faecal samples
      from musk deer at the Sichuan Institute of Musk Deer Breeding in Dujiangyan (n =
      80) and the Maerkang Breeding Institute (n = 143). Five (2.24%) faecal samples
      were positive for G. duodenalis; three belonged to assemblage E, and two belonged
      to assemblage A based on the sequence analysis of the beta-giardin (bg) gene. One
      sample each was found to be positive based on the glutamate dehydrogenase (gdh)
      and triosephosphate isomerase (tpi) gene, respectively. Thirty-eight (17.04%)
      faecal samples were found to be E. bieneusi-positive based on the internal
      transcribed spacer (ITS) sequence, and only SC03 genotype was identified, which
      belonged to the zoonotic group 1 according to the phylogenic analysis. The
      infection rates were significantly different among the different geographical
      areas and age groups but had no apparent association with gender or clinical
      symptoms. CONCLUSIONS: To our knowledge, this was the first molecular
      characterisation of G. duodenalis and E. bieneusi in musk deer. Identification of
      the zoonotic genotypes indicated a potential public health threat, and our study
      suggested that the forest musk deer is an important carrier of these parasites.

PMID- 29580295
TI  - Correction to: Cohort profile: the Saskatchewan Rural Health Study-adult
      component.
AB  - Following publication of the original article [1] the authors notified Production
      that the names of three authors-Valerie Elliot, Louise Hagel, and Roland Dyck-had
      been unintentionally omitted in the final online version of the manuscript. The
      corrected author list is shown in this Correction.

PMID- 29580296
TI  - Spatial distribution of leprosy in India: an ecological study.
AB  - BACKGROUND: As leprosy elimination becomes an increasingly realistic goal, it is
      essential to determine the factors that contribute to its persistence. We
      evaluate social and economic factors as predictors of leprosy annual new case
      detection rates within India, where the majority of leprosy cases occur. METHODS:
      We used correlation and linear mixed effect regressions to assess whether
      poverty, illiteracy, nighttime satellite radiance (an index of development), and
      other covariates can explain district-wise annual new case detection rate and
      Grade 2 disability diagnoses. RESULTS: We find only weak evidence of an
      association between poverty and annual new case detection rates at the district
      level, though illiteracy and satellite radiance are statistically significant
      predictors of leprosy at the district level. We find no evidence of rapid decline
      over the period 2008-2015 in either new case detection or new Grade 2 disability.
      CONCLUSIONS: Our findings suggest a somewhat higher rate of leprosy detection, on
      average, in poorer districts; the overall effect is weak. The divide between
      leprosy case detection and true incidence of clinical leprosy complicates these
      results, particularly given that the detection rate is likely disproportionately
      lower in impoverished settings. Additional information is needed to distinguish
      the determinants of leprosy case detection and transmission during the
      elimination epoch.

PMID- 29580297
TI  - Clinical impact of "pure" empirical catheter ablation of slow-pathway in patients
      with non-ECG documented clinical on-off tachycardia.
AB  - BACKGROUND: Catheter ablation of slow-pathway (CaSP) has been reported to be
      effective in patients with dual atrioventricular nodal conduction properties (dcp
      AVN) and clinical ECG documentation but without the induction of tachycardia
      during electrophysiological studies (EPS). However, it is unknown whether CaSP is
      beneficial in the absence of pre-procedural ECG documentation and without the
      induction of tachycardia during EPS. The aim of this study was to evaluate long
      term results after a "pure" empirical CaSP (peCaSP). METHODS: 334 consecutive
      patients who underwent CaSP (91 male, 47.5 +/- 17.6 years) were included in this
      study. Sixty-three patients (19%) who had no pre-procedural ECG documentation,
      and demonstrated dcp-AVN with a maximum of one echo-beat were assigned to the
      peCaSP group. The remaining 271 patients (81%) were assigned to the standard CaSP
      group (stCaSP). Clinical outcomes of the two groups were compared, based on ECG
      documented recurrence or absence of tachycardia and patients' recorded symptoms.
      RESULTS: CaSP was performed in all patients without any major complications
      including atrioventricular block. During follow-up (909 +/- 435 days), 258
      patients (77%) reported complete cessation of clinical symptoms. There was no
      statistically significant difference in the incidence of AVNRT recurrence between
      the peCaSP and stCaSP groups (1/63 [1.6%] vs 3/271 [1.1%], P = 0.75). Complete
      cessation of clinical symptoms was noted significantly less frequently in
      patients after peCaSP (39/63 [62%] vs 219/271 [81%], P = 0.0013). The incidence
      of non-AVNRT atrial tachyarrhythmias (AT) was significantly higher in patients
      after peCaSP (5/63 [7.9%] vs 1/271 [0.4%], P = 0.0011). CONCLUSION: A higher
      incidence of other AT and subjective symptom persistence are demonstrated after
      peCaSP, while peCaSP improves clinical symptoms in 60% of patients with non
      documented on-off tachycardia.

PMID- 29580298
TI  - Submental liposuction for the management of lymphedema following head and neck
      cancer treatment: a randomized controlled trial.
AB  - BACKGROUND: Patients who have undergone treatment for head and neck cancer are at
      risk for neck lymphedema, which can severely affect quality of life. Liposuction
      has been used successfully in cancer patients who suffer from post-treatment limb
      lymphedema. The purpose of our study was to review the outcomes of head and neck
      cancer patients at our center who have undergone submental liposuction for post
      treatment lymphedema and compare their subsequent results with a control group.
      METHODS: All head and neck cancer patients at an oncology center in tertiary
      hospital setting who complained to their attending surgeon or radiation
      oncologist regarding cervical lymphedema secondary to head and neck cancer
      treatment, and had been disease-free for a minimum of one year, with no previous
      facial plastic surgical procedures were eligible for inclusion into the study.
      Study design was a non-blinded randomized controlled trial. Twenty patients were
      randomized into a treatment arm (underwent submental liposuction n = 10) and
      control arm (n = 10). Both groups of patients completed two surveys (Modified
      Blepharoplasty Outcome Evaluation and the validated Derriford Appearance Scale)
      on initial office visit after consenting for the trial. The treatment group then
      completed the surveys 6 months post-operatively while the control group filled
      the surveys 6 months after the initial assessment but had no intervention. Mann
      Whitney U tests were performed to compare the responses of those that did and did
      not receive liposuction. RESULTS: Our study demonstrated a statistically
      significant improvement in patients' self-perception of appearance and
      statistically significant subjective scoring of appearance following submental
      liposuction. CONCLUSIONS: Submental liposuction is an effective and safe
      procedure to improves the quality of life for head and neck cancer patients
      suffering from post-treatment lymphedema.

PMID- 29580299
TI  - A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated
      Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of
      Multidrug-Resistant Acinetobacter baumannii.
AB  - OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case
      fatality rate and length of stay) and economic burden (healthcare cost) of
      healthcare-associated infections (HAIs) due to multidrug-resistant organisms
      (MDROs) among patients in intensive care units (ICUs) in Southeast
      Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature
      search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases
      from their inception through September 30, 2016. Clinical and economic burdens
      and study quality were assessed for each included study.RESULTSIn total, 41
      studies met our inclusion criteria; together, 22,876 ICU patients from 7
      Southeast Asian countries were included. The cumulative incidence of HAI caused
      by A. baumannii (AB) in Southeast Asia is substantially higher than has been
      reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and
      multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response
      relationship between different degrees of drug resistance and excess mortality
      due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence
      interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively
      drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB
      (PDR-AB). There is, however, a paucity of published data on additional length of
      stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the
      challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram
      negative bacteria are abundant and have a strong impact on society. With our
      findings, we hope to draw the attention of clinicians and policy makers to the
      problem of antibiotic resistance and to issue a call for action in the management
      of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.

PMID- 29580300
TI  - Association study highlights the influence of ELOVL fatty acid elongase 6 gene
      region on backfat fatty acid composition in Large White pig breed.
AB  - Dietary fatty acid (FA) composition has an impact on human health. There is an
      increasing request from consumers for healthier food and pork industry must
      respond to it without worsening performance and the technological properties of
      pork products. The inclusion of genetic markers for carcass FA composition in pig
      selection schemes could be a useful tool to reach the right balance between
      unsaturated and saturated FAs to satisfy market demands. With the aim of finding
      genomic regions associated with porcine backfat FA composition, a genome-wide
      association study was performed on 798 Italian Large White pigs genotyped using
      Illumina PorcineSNP60 k. The strongest associations with backfat contents of
      palmitic, palmitoleic, oleic, medium-chain and long-chain FAs were found for the
      Sus scrofa chromosome (SSC) 8 region located at 119 to 122 Mb, where the gene
      ELOVL FA elongase 6 is mapped. Palmitic, palmitoleic, stearic and oleic acid
      contents were also found associated with SSC14, in particular with the genomic
      region at 121 to 124 Mb, where stearoyl-CoA desaturase Delta9 gene lies. On the
      other hand, the genomic regions associated with backfat contents of arachidic,
      arachidonic, n-6 and n-3 FAs showed to harbour mainly genes involved in dietary
      lipids and carbohydrates digestion, absorption and utilisation. To our knowledge,
      this is the first study performed in Large White pigs identifying markers and
      genomic regions associated with backfat FA composition. The results validate in
      Large White some associations previously detected in other pig breeds and
      indicate the involvement of distinct metabolic pathways in the deposition pattern
      of essential and non-essential FAs.

PMID- 29580302
TI  - Determinants of poor sleep quality in elderly patients with diabetes mellitus,
      hyperlipidemia and hypertension in Singapore.
AB  - : AimThe objective of this study was to assess determinants of poor sleep quality
      which is an under-diagnosed and under-treated problem in elderly patients with
      diabetes mellitus, hyperlipidemia and hypertension. BACKGROUND: Poor sleep
      quality is linked to decreased quality of life, increased morbidity and
      mortality. Poor sleep quality is common in the elderly population with associated
      cardiometabolic risk factors such as diabetes, hyperlipidemia and hypertension.
      METHODS: This is a cross-sectional study undertaken in the primary healthcare
      setting (Singhealth Polyclinics-Outram) in Singapore. Singaporeans aged 65 years
      and above who had at least one of the three cardiometabolic risk factors
      (diabetes, hypertension and hyperlipidemia) were identified. Responders' sleep
      quality was assessed using the Pittsburgh Sleep Quality Index (PSQI)
      questionnaire and were divided into those with good quality sleep and those with
      poor quality sleep, based on the PSQI score. Information on demographics, co
      morbidities and lifestyle practices were collected. Descriptive and multivariate
      analyses of determinants of poor sleep were determined.FindingsThere were 199
      responders (response rate 88.1%). Nocturia (adjusted prevalence rate ratio 1.54,
      95% confidence interval 1.06-2.26) was found to be associated with an increased
      risk of poor sleep quality in elderly patients with diabetes mellitus,
      hypertension and hyperlipidaemia. Nocturia, a prevalent problem in the Asian
      elderly population, has been found to be associated with poor sleep quality in
      our study. Hence, it is imperative to identify and treat patients with nocturia
      to improve sleep quality among them.

PMID- 29580301
TI  - Changes in the nutritional quality of fast-food items marketed at restaurants,
      2010 v. 2013.
AB  - OBJECTIVE: To examine the nutritional quality of menu items promoted in four (US)
      fast-food restaurant chains (McDonald's, Burger King, Wendy's, Taco Bell) in 2010
      and 2013. DESIGN: Menu items pictured on signs and menu boards were recorded at
      400 fast-food restaurants across the USA. The Nutrient Profile Index (NPI) was
      used to calculate overall nutrition scores for items (higher scores indicate
      greater nutritional quality) and was dichotomized to denote healthier v. less
      healthy items. Changes over time in NPI scores and energy of promoted foods and
      beverages were analysed using linear regression. SETTING: Four hundred fast-food
      restaurants (McDonald's, Burger King, Wendy's, Taco Bell; 100 locations per
      chain). SUBJECTS: NPI of fast-food items marketed at fast-food restaurants.
      RESULTS: Promoted foods and beverages on general menu boards and signs remained
      below the 'healthier' cut-off at both time points. On general menu boards,
      pictured items became modestly healthier from 2010 to 2013, increasing (mean
      (se)) by 3.08 (0.16) NPI score points (P<0.001) and decreasing (mean (se)) by 130
      (15) kJ (31.1 (3.65) kcal; P<0.001). This pattern was evident in all chains
      except Taco Bell, where pictured items increased in energy. Foods and beverages
      pictured on the kids' section showed the greatest nutritional improvements.
      Although promoted foods on general menu boards and signs improved in nutritional
      quality, beverages remained the same or became worse. CONCLUSIONS: Foods, and to
      a lesser extent, beverages, promoted on menu boards and signs in fast-food
      restaurants showed limited improvements in nutritional quality in 2013 v. 2010.

PMID- 29580303
TI  - Healthy changes in some cardiometabolic risk factors accompany the higher
      summertime serum 25-hydroxyvitamin D concentrations in Iranian children: National
      Food and Nutrition Surveillance.
AB  - OBJECTIVE: To investigate seasonal variations of vitamin D status at different
      latitudes and if these changes are accompanied by corresponding variations in
      certain health parameters in children living in a broad latitudinal range in
      Iran. DESIGN: Longitudinal study. SUBJECTS: In total, 530 apparently healthy
      children aged 5-18 years were randomly selected from six regions of Iran with a
      latitudinal gradient from 29 degrees N to 37.5 degrees N. All anthropometric and
      biochemical assessments were performed twice during a year (summer, winter). High
      BMI (Z-score >1), low HDL cholesterol (150 mg/dl) were considered cardiometabolic
      risk factors. RESULTS: Serum 25-hydroxyvitamin D (25(OH)D) showed between-season
      variation, with significantly higher concentrations (mean (sd)) in summer v.
      winter (43 (29) v. 27 (18) nmol/l; P33 degrees N v. <33 degrees N: 4.5; 0.09,
      9.0; P=0.04) were predictors of change of serum 25(OH)D between two seasons.
      CONCLUSIONS: Summertime improvement of vitamin D status was accompanied by
      certain improved cardiometabolic risk factors, notably serum TAG, total
      cholesterol and BMI, in children.

PMID- 29580304
TI  - Impact of Discontinuing Contact Precautions for Methicillin-Resistant
      Staphylococcus aureus and Vancomycin-Resistant Enterococcus: An Interrupted Time
      Series Analysis.
AB  - : OBJECTIVETo investigate the impact of discontinuing contact precautions among
      patients infected or colonized with methicillin-resistant Staphylococcus aureus
      (MRSA) or vancomycin-resistant Enterococcus (VRE) on rates of healthcare
      associated infection (HAI). DESIGN: Single-center, quasi-experimental study
      conducted between 2011 and 2016.METHODSWe employed an interrupted time series
      design to evaluate the impact of 7 horizontal infection prevention interventions
      across intensive care units (ICUs) and hospital wards at an 865-bed urban,
      academic medical center. These interventions included (1) implementation of a
      urinary catheter bundle in January 2011, (2) chlorhexidine gluconate (CHG)
      perineal care outside ICUs in June 2011, (3) hospital-wide CHG bathing outside of
      ICUs in March 2012, (4) discontinuation of contact precautions in April 2013 for
      MRSA and VRE, (5) assessments and feedback with bare below the elbows (BBE) and
      contact precautions in August 2014, (6) implementation of an ultraviolet-C
      disinfection robot in March 2015, and (7) 72-hour automatic urinary catheter
      discontinuation orders in March 2016. Segmented regression modeling was performed
      to assess the changes in the infection rates attributable to the
      interventions.RESULTSThe rate of HAI declined throughout the study period.
      Infection rates for MRSA and VRE decreased by 1.31 (P=.76) and 6.25 (P=.21) per
      100,000 patient days, respectively, and the infection rate decreased by 2.44 per
      10,000 patient days (P=.23) for device-associated HAI following discontinuation
      of contact precautions.CONCLUSIONThe discontinuation of contact precautions for
      patients infected or colonized with MRSA or VRE, when combined with horizontal
      infection prevention measures was not associated with an increased incidence of
      MRSA and VRE device-associated infections. This approach may represent a safe and
      cost-effective strategy for managing these patients.Infect Control Hosp Epidemiol
      2018;39:676-682.

PMID- 29580305
TI  - Genotyping of individual Ceratonova shasta (Cnidaria: Myxosporea) myxospores
      reveals intra-spore ITS-1 variation and invalidates the distinction of genotypes
      II and III.
AB  - Genotypes of the myxosporean parasite Ceratonova shasta are defined by the number
      of ATC repeats in the parasite's ribosomal DNA internal transcribed spacer region
      1. These genotypes correlate with specific salmonid fish hosts. We observed coho
      salmon (Oncorhynchus kisutch) and rainbow trout (Oncorhynchus mykiss) with
      mixtures of genotypes II and III, and assumed that this was a consequence of fish
      having an aggregate infection from multiple individual parasites. We hypothesized
      that although multiple ITS copies are present within a parasite spore, the DNA
      sequences of these copies are identical, and thus individual C. shasta spores are
      a single genotype. We tested this by extracting and sequencing DNA from
      individual myxospores. We trialed three approaches for in-tube DNA extraction;
      digestion with proteinase K was superior to simply rehydrating spores, or
      incubation in the buffer. Sequences from 14 myxospores were each a mixture of
      genotypes II and III. Therefore, intra-genomic ribosomal DNA variants exist
      within individual parasite spores, and II and III should no longer be regarded as
      discrete C. shasta genotypes. This single-spore genotyping approach will be a
      useful tool for testing validity of other C. shasta genotypes, and for correctly
      matching genotype with phenotype for mixed infections of other myxozoan species.

PMID- 29580306
TI  - Assessment of thyroid function in children, adults and pregnant and lactating
      women after long-term salt iodisation measurements.
AB  - Universal salt iodisation (USI) has been successfully implemented in China for
      more than 15 years. Recent evidence suggests that the definition of 'adequate
      iodine' (100-199 ug/l) be revised to 'sufficient iodine' (100-299 ug/l) based on
      the median urinary iodine concentration (MUI) in school-age children. The
      objective of this study was to determine the prevalence of thyroid dysfunction in
      populations after long-term salt iodisation and examine whether the definition of
      adequate iodine can be broadened to sufficient iodine based on the thyroid
      function in four population groups. A cross-sectional survey was conducted in six
      provinces in the northern, central and southern regions of China. Four population
      groups consisting of 657 children, 755 adults, 347 pregnant women and 348
      lactating women were recruited. Three spot urinary samples were collected over a
      10-d period and blood samples were collected on the 1st day. In the study, among
      the adults, pregnant women and lactating women, the prevalence rates of elevated
      thyroglobulin antibody and thyroid microsomal antibody levels were 12.4, 8.5 and
      7.8 %, and 12.1, 9.1 and 9.1 %, respectively. Abnormally high thyroid dysfunction
      prevalence was not observed after more than 15 years of USI in China because the
      thyroid dysfunction rates were all <5 %. The recommended range should be
      cautiously broadened from adequate iodine to sufficient iodine according to the
      MUI of school-age children considering the high levels of hormones and antibodies
      in the other populations. Adults, particularly pregnant women positive for
      thyroid antibodies, should be closely monitored.

PMID- 29580307
TI  - n-3 PUFA and obesity: from peripheral tissues to the central nervous system.
AB  - The current paradigms of prevention and treatment are unable to curb obesity
      rates, which indicates the need to explore alternative therapeutic approaches.
      Obesity leads to several damages to the body and is an important risk factor for
      a number of other chronic diseases. Furthermore, despite the first alterations in
      obesity being observed and reported in peripheral tissues, studies indicate that
      obesity can also cause brain damage. Obesity leads to a chronic low-grade
      inflammatory state, and the therapeutic manipulation of inflammation can be
      explored. In this context, the use of n-3 PUFA (especially in the form of fish
      oil, rich in EPA and DHA) may be an interesting strategy, as this substance is
      known by its anti-inflammatory effect and numerous benefits to the body, such as
      reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation,
      and has shown potential to help treat obesity. Thereby, the aim of this narrative
      review was to summarise the literature related to n-3 PUFA use in obesity
      treatment. First, the review provides a brief description of the obesity
      pathophysiology, including alterations that occur in peripheral tissues and at
      the central nervous system. In the sequence, we describe what are n-3 PUFA, their
      sources and their general effects. Finally, we explore the main topic linking
      obesity and n-3 PUFA. Animal and human studies were included and alterations on
      the whole organism were described (peripheral tissues and brain).

PMID- 29580308
TI  - Introduction: From "The Popularization of Science through Film" to "The Public
      Understanding of Science".
AB  - Science in film, and usual equivalents such as science on film or science on
      screen, refer to the cinematographic representation, staging, and enactment of
      actors, information, and processes involved in any aspect or dimension of science
      and its history. Of course, boundaries are blurry, and films shot as research
      tools or documentation also display science on screen. Nonetheless, they
      generally count as scientific film, and science in and on film or screen tend to
      designate productions whose purpose is entertainment and education. Moreover,
      these two purposes are often combined, and inherently concern empirical,
      methodological, and conceptual challenges associated with popularization, science
      communication, and the public understanding of science. It is in these areas that
      the notion of the deficit model emerged to designate a point of view and a mode
      of understanding, as well as a set of practical and theoretical problems about
      the relationship between science and the public.

PMID- 29580309
TI  - Harnessing the Persuasive Power of Narrative: Science, Storytelling, and Movie
      Censorship, 1930-1968.
AB  - Argument As the deficit model's failure leaves scientists searching for more
      effective communicative approaches, science communication scholars have begun
      promoting narrative as a potent persuasive tool. Narratives can help the public
      make choices by setting out a scientific issue's contexts, establishing the
      stakes involved, and offering potential solutions. However, employing narrative
      for persuasion risks embracing the same top-down communication approach
      underlying deficit model thinking. This essay explores the parallels between
      movie censorship and the current use of narrative to influence public opinion by
      examining how the Hays Office and the Catholic Legion of Decency responded to
      science in movies. I argue that deploying narratives solely as public relations
      exercises demonstrates the same mistrust of audiences that provided the
      foundation of movie censorship. But the history of movie censorship reveals the
      dangers of using narrative to remove the public's agency and to coerce them
      towards a preferred position rather than fostering their ability to come to their
      own conclusions.

PMID- 29580310
TI  - Taking Spectacle Seriously: Wildlife Film and the Legacy of Natural History
      Display.
AB  - Argument I argue through an analysis of spectacle that the relationship between
      wildlife documentary films' entertainment and educational mandates is complex and
      co-constitutive. Accuracy-based criticism of wildlife films reveals assumptions
      of a deficit model of science communication and positions spectacle as an
      external commercial pressure influencing the genre. Using the Planet Earth (2006)
      series as a case study, I describe spectacle's prominence within the recent blue
      chip renaissance in wildlife film, resulting from technological innovations and
      twenty-first-century consumer and broadcast market contexts. I connect spectacle
      in contemporary wildlife films to its relevant precursors within natural history,
      situating spectacle as a central feature of natural history display designed to
      inspire awe and wonder in audiences. I show that contemporary documentary
      spectacle is best understood as an opportunity for affective knowing rather than
      a constraint on accuracy; as a result, spectacle contributes to the virtuous
      inter-reinforcement of entertainment and education at work in blue-chip wildlife
      films.

PMID- 29580311
TI  - Configuring Epistemic Authority: The Significance of Film Style in Documentaries
      about Science.
AB  - Argument Among the many limitations of the deficit model of science communication
      is its inability to account for the qualities of communication products that
      arise from creative decisions about form and style. This paper examines two
      documentaries about the nature of time - Patricio Guzman's Nostalgia for the
      Light and the first episode of the BBC's Wonders of the Universe series - in
      order to consider how film style inflects science with different meanings. The
      analysis pays particular attention to the ways in which authority is assigned
      between film author, narrator, and depicted subjects and the degree to which
      different film styles promote epistemological certainty or hesitancy.

PMID- 29580312
TI  - The Shifting Aesthetics of Expertise in the Sharing Economy of Scientific
      Medicine.
AB  - Argument The deficit model of science communication assumes that the creation and
      dissemination of knowledge is limited to researchers with formal credentials.
      Recent challenges to this model have emerged among "e-patients" who develop
      extensive online activist communities, demand access to their own health data,
      conduct crowd-sourced experiments, and "hack" health problems that traditional
      medical experts have failed to solve. This article explores the aesthetics of
      medical media that enact the transition from a deficit model to a patient-driven
      model of visual representation and health communication. I present a framework
      for understanding the role of film and video in patient movements by analyzing
      the historical transition from researchers filming patients as nameless,
      voiceless human research subjects to patients recording their own health
      narratives through activist cinematography. By comparing several approaches to
      patient-centered video, I argue that imperfect production aesthetics play a
      critically important role in establishing the credibility of health
      communications.

PMID- 29580313
TI  - The Changing Nature of Modernization Discourses in Documentary Films.
AB  - Argument Franco's fascist regime in Spain (1939-1975) offers the possibility of
      exploring the complex relationship between media communication practices and the
      processes of production, circulation, and management of knowledge. The regime
      persistently used film, and later on television, as indoctrination and
      disciplining devices. These media thus served to shape the regime's
      representation, which largely relied on the generation of positive attitudes of
      adherence to the rulers through people's submission and obedience to experts.
      This article examines the changing nature of modernization discourses and
      practices, as a fundamental element of the regime's propaganda strategies, and as
      portrayed in documentaries produced under its rule. The rhetoric of modernization
      involved an explicit deficit model of knowledge management, which aimed at
      legitimating the regime's deeds and policies in its first decades, as we shall
      see regarding colonial-medical documentaries produced for the official newsreel
      in the 1940s. However, the focus of such rhetoric, despite its enduring political
      aims, had to somehow open up as the relationship between experts and non-experts
      changed, both in epistemological and practical terms, such as in wildlife
      documentary films produced for television in the 1970s, the regime's last decade.

PMID- 29580314
TI  - Accuracy, Authenticity, Fidelity: Aesthetic Realism, the "Deficit Model," and the
      Public Understanding of Science.
AB  - Argument "Deficit model" designates an outlook on the public understanding and
      communication of science that emphasizes scientific illiteracy and the need to
      educate the public. Though criticized, it is still widespread, especially among
      scientists. Its persistence is due not only to factors ranging from scientists'
      training to policy design, but also to the continuance of realism as an aesthetic
      criterion. This article examines the link between realism and the deficit model
      through discussions of neurology and psychiatry in fiction film, as well as
      through debates about historical movies and the cinematic adaptation of
      literature. It shows that different values and criteria tend to dominate the
      realist stance in different domains: accuracy for movies concerning neurology and
      psychiatry, authenticity for the historical film, and fidelity for adaptations of
      literature. Finally, contrary to the deficit model, it argues that the cinema is
      better characterized by a surplus of meaning than by informational shortcomings.

PMID- 29580315
TI  - Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for
      histochemical analysis and serodiagnosis of clonorchiasis.
AB  - Due to the lack of an effective prophylactic intervention and diagnosis, human
      liver fluke Clonorchis sinensis continues to afflict a large human population,
      causing a chronic inflammatory bile duct disease. With an aim to identify target
      antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3)
      was successfully expressed in soluble form in Escherichia coli by fusion to an
      RNA-interacting domain derived from human Lys-tRNA synthetase and purified by
      Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of
      mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C.
      sinensis. Histochemical analysis showed that CsAK3 was localized to the
      subtegumental tissue of C. sinensis and was excreted into the bile duct of the
      host. When tested against sera from various parasite-infected patients by enzyme
      linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to
      C. sinensis-infected sera. The results suggest that CsAK3, either alone or in
      combination with other antigens, could be used for improving the clinical
      diagnosis of clonorchiasis.

PMID- 29580316
TI  - Interventions to address household food insecurity in high-income countries.
AB  - Household food insecurity is a serious public health concern in high-income
      countries. Canada and the USA regularly monitor household food insecurity, while
      in other countries, such as the UK, it has been the rapid rise of food bank usage
      that has drawn increased attention to this longstanding, but largely overlooked,
      problem. This review evaluates evidence on interventions intended to reduce
      household food insecurity in high-income countries. Research on social protection
      interventions suggests both cash transfers and food subsidies (e.g. the US
      Supplement Nutrition and Assistance Programme) reduce household food insecurity.
      In contrast, research on community-level interventions, such as food banks and
      other food programmes, suggests limited impacts. Although food banks have become
      a common intervention for food insecurity in high-income countries, evidence
      suggests their reliance on donations of volunteer time and food make them
      inevitably limited in the assistance they are able to provide. The stigma people
      feel using food banks may also make them untenable. Alternatives to, or enhanced,
      food banks such as community shops or community kitchens, have become common, but
      evidence also suggests they may be limited in effectiveness if they do not reach
      people experiencing food insecurity. This review highlights the difficulty of
      trying to address household food insecurity with community-based food
      interventions when solutions likely lie upstream in social protection policies.

PMID- 29580317
TI  - Streptomyces salilacus sp. nov., an actinomycete isolated from a salt lake.
AB  - The taxonomic position of a novel actinomycete, strain TRM 41337T, isolated from
      sediment of a salt lake, Xiaoerkule Lake, Xinjiang, China, was determined by a
      polyphasic approach. Strain TRM 41337T grew optimally at 28  degrees C and in the
      presence of 1 % (w/v) NaCl. It grew at up to pH 12. The whole-cell sugars of
      strain TRM 41337T were ribose and xylose. The diagnostic diamino acid contained
      ll-diaminopimelic acid. The polar lipids were diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylinositolmannoside and two other unidentified phospholipids. The
      predominant menaquinones were MK-9(H8), MK-9, MK-9(H4) and MK-9(H6). The major
      fatty acids were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 1 H.
      Based on morphological and chemotaxonomic characteristics, the isolate was
      determined to belong to the genus Streptomyces. The phylogenetic tree based on
      its nearly complete 16S rRNA gene sequence (1498 nt) with representative strains
      showed that the strain consistently falls into a distinct phyletic lineage
      together with Streptomyces barkulensis DSM 42082T (97.48 % similarity) and a
      subclade consisting of Streptomyces fenghuangensis GIMN 4.003T (97.20 %),
      Streptomyces macrosporus NBRC 14748T (97.14 %) and Streptomyces radiopugnans R97T
      (97.01 %). On the basis of these data, strain TRM 41337T should be designated as
      a representative of a novel species of the genus Streptomyces, for which the name
      Streptomyces salilacus sp. nov. is proposed. The type strain is TRM 41337T
      (=CCTCC AA 2015030T=KCTC 39726T).

PMID- 29580318
TI  - alpha7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in
      Cholestatic Bile Duct-Ligated Mice.
AB  - alpha7-nAChR is a nicotinic acetylcholine receptor [specifically expressed on
      hepatic stellate cells (HSCs), Kupffer cells, and cholangiocytes] that regulates
      inflammation and apoptosis in the liver. Thus, targeting alpha7-nAChR may be
      therapeutic in biliary diseases. Bile duct ligation (BDL) was performed on wild
      type (WT) and alpha7-nAChR-/- mice. We first evaluated the expression of alpha7
      nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to
      assess intrahepatic bile duct mass (IBDM), and Sirius Red staining was performed
      to quantify the amount of collagen deposition. Immunofluorescence was performed
      to assess colocalization of alpha7-nAChR with bile ducts (costained with CK-19)
      and HSCs (costained with desmin). The mRNA expression of alpha7-nAChR, Ki-67/PCNA
      (proliferation), fibrosis genes (TGF-beta1, fibronectin-1, Col1alpha1, and alpha
      SMA), and inflammatory markers (IL-6, IL-1beta, and TNF-alpha) was measured by
      real-time PCR. Biliary TGF-beta1 and hepatic CD68 (Kupffer cell marker)
      expression was assessed using IHC. alpha7-nAChR immunoreactivity was observed in
      both bile ducts and HSCs and increased following BDL. alpha7-nAChR-/- BDL mice
      exhibited decreased (i) bile duct mass, liver fibrosis, and inflammation, and
      (ii) immunoreactivity of TGF-beta1 as well as expression of fibrosis genes
      compared to WT BDL mice. alpha7-nAChR activation triggers biliary proliferation
      and liver fibrosis and may be a therapeutic target in managing extrahepatic
      biliary obstruction.

PMID- 29580319
TI  - Liver and Pancreas: Do Similar Embryonic Development and Tissue Organization Lead
      to Similar Mechanisms of Tumorigenesis?
AB  - The liver and pancreas are closely associated organs that share a common
      embryological origin. They display amphicrine properties and have similar
      exocrine organization with parenchymal cells, namely, hepatocytes and acinar
      cells, secreting bile and pancreatic juice into the duodenum via a converging
      network of bile ducts and pancreatic ducts. Here we compare and highlight the
      similarities of molecular mechanisms leading to liver and pancreatic cancer
      development. We suggest that unraveling tumor development in an organ may provide
      insight into our understanding of carcinogenesis in the other organ.

PMID- 29580320
TI  - ICTV Virus Taxonomy Profile: Avsunviroidae.
AB  - Members of the family Avsunviroidae have a single-stranded circular RNA genome
      that adopts a rod-like or branched conformation and can form, in the strands of
      either polarity, hammerhead ribozymes involved in their replication in plastids
      through a symmetrical RNA-RNA rolling-circle mechanism. These viroids lack the
      central conserved region typical of members of the family Pospiviroidae. The
      family Avsunviroidae includes three genera, Avsunviroid, Pelamoviroid and
      Elaviroid, with a total of four species. This is a summary of the ICTV Report on
      the taxonomy of the family Avsunviroidae, which is available at
      http://www.ictv.global/report/avsunviroidae.

PMID- 29580321
TI  - Salinivirga fredricksonii gen. nov., sp. nov., a heterotrophic halophile isolated
      from a photosynthetic mat, a member of a novel lineage (Salinarimonadaceae fam.
      nov.) within the order Rhizobiales, and reclassification of the genus
      Salinarimonas Liu et al. 2010 into Salinarimonadaceae.
AB  - A halophilic bacterial strain, HL-109T, was isolated from the unicyanobacterial
      consortium UCC-O, which was obtained from the photosynthetic mat of Hot Lake
      (Washington, USA). A polyphasic approach using phenotypic, genotypic and
      chemotaxonomic data was used to classify the strain within the order Rhizobiales.
      The organism stained Gram-negative and was a moderate thermophile with a growth
      optimum of 45  degrees C. It was obligately aerobic, heterotrophic and
      halophilic, growing in both NaCl and MgSO4 brines. The novel isolate had a
      polymorphic cellular morphology of short rods with occasional branching, and
      cells were monotrichous. The major fatty acids detected were C18 : 1, C18 : 0,
      C16 : 0 and C18 : cyc. Phylogenetic analysis of the 16S rRNA gene placed the
      strain in the order Rhizobiales and it shared 94 % identity with the type strain
      of its nearest relative, Salinarimonas ramus. Morphological, chemotaxonomic and
      phylogenetic results did not affiliate the novel organism with any of the
      families in the Rhizobiales; therefore, HL-109T is representative of a new
      lineage, for which the name Salinivirga fredricksonii gen. nov., sp. nov. is
      proposed, with the type strain HL-109T (=JCM 31876T=DSM 102886T). In addition,
      examination of the phylogenetics of strain HL-109T and its nearest relatives,
      Salinarimonas ramus and Salinarimonasrosea, demonstrates that these halophiles
      form a clade distinct from the described families of the Rhizobiales. We further
      propose the establishment of a new family, Salinarimonadaceae fam. nov., to
      accommodate the genera Salinivirga and Salinarimonas (the type genus of the
      family).

PMID- 29580322
TI  - Two novel totiviruses in the white-backed planthopper, Sogatella furcifera.
AB  - There is little information about commensal viruses in the white-backed
      planthopper, Sogatella furcifera, although it is an important agricultural
      insect. Here, two novel double-stranded RNA viruses related to the viruses in the
      family Totiviridae were identified using next-generation sequencing and
      tentatively named Sogatella furcifera totivirus 1 and 2 (SfTV1 and SfTV2). Their
      complete genomes consist of 6310 and 6303 nt, respectively, showing typical
      genomic features with viruses in the family Totiviridae. Identity, phylogenetic
      and conserved sequence analyses showed that SfTV1, SfTV2 and three other insect
      viruses may form a proposed novel genus of the family Totiviridae. Vertical
      transmission of the two viruses was highly efficient, and they were detected in
      all insect tissues and developmental stages, with the highest titres in the adult
      and in the haemolymph and reproductive organs. To our knowledge, this is the
      first report of viruses in the family Totiviridae found in a hemipteran insect.

PMID- 29580323
TI  - Aquimarina celericrescens sp. nov., isolated from seawater.
AB  - An orange-coloured, slender rod-shaped, gliding bacterium, designated NS08T, was
      isolated from coastal water of Xiaoshi Island, Weihai, China (37 degrees  31'
      36'' N 122 degrees  00' 58'' E). Cells were Gram-stain-negative, non-spore
      forming, non-flagellated, aerobic, catalase-positive and oxidase-negative. Growth
      occurred at 10-37  degrees C (optimum 30  degrees C), in the presence of 1.0-5.0
      % (w/v) NaCl (optimum 2.0-3.0 %) and at pH 6.5-9.0 (optimum pH 7.0-7.5).
      Carotenoid pigments were produced but flexirubin-type pigments were not. The
      major fatty acids (>10 %) were iso-C15 : 0 and iso-C17 : 0 3-OH. The sole
      isoprenoid quinone of strain NS08T was menaquinone MK-6 and the DNA G+C content
      was 39.4 mol%. The polar lipid compositions of strain NS08T and the type strain
      of the type species of the genus Aquimarina, Aquimarina muelleri KCTC 12285T,
      were very similar with phosphatidylethanolamine, an unidentified aminolipid and
      two unknown polar lipids as the major components. A phylogenetic tree based on
      16S rRNA gene sequences showed that strain NS08T formed an evolutionary lineage
      within the genus Aquimarina and shared the highest level of similarity to A.
      versatilis JCM 19528T (96.0 %) while level to A. muelleri KCTC 12285T was 95.0 %.
      Phenotypic characteristics distinguished strain NS08T from described members of
      the genus Aquimarina. On the basis of the evidence presented in this study,
      strain NS08T represents a novel species of the genus Aquimarina, for which the
      name Aquimarina celericrescens sp. nov. is proposed. The type strain is NS08T
      (=KCTC 52897T=MCCC 1H00191T).

PMID- 29580324
TI  - Emended description of Salinivibrio proteolyticus, including Salinivibrio
      costicola subsp. vallismortis and five new isolates.
AB  - We carried out a comparative taxonomic study of Salinivibrio proteolyticus and
      Salinivibrio costicola subsp. vallismortis, as well as of five halophilic strains
      (IB574, IB872, PR5, PR919 and PR932), isolated from salterns in Spain and Puerto
      Rico that were closely related to these bacteria. Multilocus sequence analysis of
      concatenated gyrB, recA, rpoA and rpoD housekeeping genes showed that they
      constituted a single cluster separate from the other species and subspecies of
      Salinivibrio. Experimental and in silico DNA-DNA hybridization studies indicated
      that they are members of the same species, with relatedness of 100-74 % and 97.8
      70.0 %, respectively. The average nucleotide identity (ANI) determined for these
      strains was 99.7-95.6 % for ANIb and 99.7-95.7 % for OrthoANI. However, the ANI
      values for S. costicolasubsp.vallismortis DSM 8285T with respect to S.
      costicolasubsp.costicola DSM 11403T and S. costicolasubsp.alcaliphilus DSM 16359T
      were 78.7 and 78.9 % (ANIb) and 79.4 and 79.4 % (OrthoANI), respectively. The
      phylogenomic tree based on 1072 concatenated orthologous single-copy core genes
      confirmed that S. proteolyticus, S. costicolasubsp.vallismortis and the five new
      isolates constitute a coherent single phylogroup, separated from the other
      species and subspecies of Salinivibrio. All these data indicate that S.
      costicolasubsp.vallismortis is a heterotypic synonym of S. proteolyticus and we
      propose an emended description of this species.

PMID- 29580339
TI  - Endovascular Relining of a Perigraft Hygroma After Open Abdominal Aortic Aneurysm
      Repair.

PMID- 29580325
TI  - Understanding ACGME Scholarly Activity Requirements for General Surgery Programs
      in the Era of Single Accreditation and the Next Accreditation System.
AB  - Becoming compliant with the Accreditation Council for Graduate Medical Education
      (ACGME) requirements for scholarly activity and remaining compliant over time
      requires time and attention to the development of an environment of inquiry,
      which is reflected in detailed documentation submitted in program applications
      and annual updates. Since the beginning of the next accreditation system, all
      ACGME programs have been required to submit evidence of scholarly activity of
      both residents and faculty on an annual basis. Since 2014, American Osteopathic
      Association-accredited programs have been able to apply for ACGME accreditation
      under the Single Graduate Medical Education Accreditation initiative. The
      Residency Program Director, Chair, Designated Institutional Official, Faculty,
      and coordinator need to work cohesively to ensure compliance with all program
      requirements, including scholarly activity in order for American Osteopathic
      Association-accredited programs to receive Initial ACGME Accreditation and for
      current ACGME-accredited programs to maintain accreditation. Fortunately, there
      are many ways to show the type of scholarly activity that is required for the
      training of surgeons. In this article, we will review the ACGME General Surgery
      Program Requirements and definitions of scholarly activity. We will also offer
      suggestions for how programs may show evidence of scholarly activity.

PMID- 29580341
TI  - Laparoscopic Heller Myotomy with Anterior Fundoplication Improves Frequency and
      Severity of Symptoms of Achalasia, Regardless of Preoperative Severity Determined
      by Esophagography.
AB  - This study was undertaken to determine whether postoperative outcomes after
      laparoscopic Heller myotomy with anterior fundoplication could be predicted by
      preoperative findings on esophagography. Preoperative barium esophagograms of 135
      patients undergoing laparoscopic Heller myotomy with anterior fundoplication were
      reviewed. The number of esophageal curves, esophageal width, and angulation of
      the gastroesophageal junction (GEJ) were determined; correlations between these
      determined parameters and symptoms were assessed using linear regression
      analysis. The number of esophageal curves correlated with the preoperative
      frequency of dysphagia, vomiting, chest pain, regurgitation, and heartburn. The
      width of the esophagus negatively correlated with the preoperative frequency of
      regurgitation. The angulation of the GEJ did not correlate with preoperative
      symptoms. Laparoscopic Heller myotomy with anterior fundoplication significantly
      reduced the frequency and severity of all symptoms, regardless of the number of
      esophageal curves, esophageal width, or angulation of the GEJ. Laparoscopic
      Heller myotomy with anterior fundoplication provides dramatic palliation for
      achalasia. More esophageal curves on preoperative esophagography correlate well
      with the frequency of a broad range of preoperative symptoms, including the
      frequency of dysphagia and regurgitation. Patients experience dramatically
      improved frequency and severity of symptoms after laparoscopic Heller myotomy
      with anterior fundoplication for achalasia regardless of the number of esophageal
      curves, esophageal width, or the angulation of the GEJ. Findings on barium
      esophagogram, in evaluating achalasia, should not deter the application of
      laparosocopic Heller myotomy with anterior fundoplication.

PMID- 29580342
TI  - Early Uncomplicated Appendicitis-Who Can We Treat Nonoperatively?
AB  - This study evaluated nonoperative treatment for mild appendicitis and reviewed
      selection criteria to be used in introducing this option into clinical practice.
      A retrospective review of 73 consecutive cases of appendicitis treated by a
      single surgeon from 2011 to 2013 was completed. Patients who were diagnosed with
      mild appendicitis meeting the criteria of an APPENDICITIS scoring algorithm
      proposed in this manuscript were considered for nonoperative management. An
      additional 17 patients with mild appendicitis were offered and successfully
      treated nonoperatively between 2014 and 2016 and reviewed. Of these original 73
      patients, 37 had moderate to severe appendicitis and directly underwent
      appendectomy. The remaining patients were diagnosed with mild appendicitis and
      considered eligible for nonoperative management. Of these, 14 patients were
      offered nonoperative therapy. Thirteen responded successfully; one patient
      responded partially, but later opted for surgery. In 2014, this scoring system
      and preliminary results were shared with the other surgeons in our department.
      Nonoperative management was then selectively adopted by a few of the surgeons
      from 2014 to 2016 with another 17 patients (APPENDICITIS score of 0 or 1) being
      offered and successfully managed nonoperatively. Patients with mild or early
      appendicitis can be successfully managed nonoperatively. A proposed APPENDICITIS
      scoring system may provide a helpful mnemonic for successfully selecting patients
      for this option.

PMID- 29580343
TI  - Incidence and Impact of Variant Celiacomesenteric Vascularization and Vascular
      Stenosis on Pancreatic Surgery Outcomes: Personal Experience.
AB  - Ischemic complications after pancreatic surgery can raise postoperative mortality
      from 4 to 83 per cent. Variants in vascular anatomy play a major role in
      determining such complications, but they have been only occasionally reported in
      the literature. We retrospectively analyzed 100 records of patients consecutively
      treated between January 2011 and December 2013 for resectable malignant diseases
      who underwent pancreaticoduodenectomy (PD) or total pancreatectomy to state the
      statistical impact of anatomical vascular variations in surgical outcomes (mean
      surgical timing, mean blood loss during surgery, and postoperative major
      complications onset) and to state whether preoperatively undetected vascular
      anomalies (VA) can raise the risk of postoperative ischemic complications. PD was
      performed in 89 patients, requiring multiorgan resections in three cases and
      total pancreatectomy was performed in 11 cases, which was associated to
      splenectomy in four patients. Incidence of VA was 25/100 (25%), whereas in 18/25
      cases (72%) they were detected by preoperative radiologic setting. Their presence
      in patients undergoing PD significantly raised mean surgical timing (P = 0.003)
      and increased mean blood loss (P < 0.0001). Preoperatively undetected VA resulted
      in a major risk of postoperative acute liver ischemia (P = 0.008).
      Celiacomesenteric aberrant anatomy was proven to be related to an increased risk
      of intraoperative complications. If undetected preoperatively, they can be
      associated with anastomotic complications and liver failure. Maximal efforts must
      be done to detect and to preserve vascular anatomy of celiacomesenteric district.

PMID- 29580344
TI  - Building a Single-Site Robotic Cholecystectomy Program in a Public Teaching
      Hospital: Is It Safe for Patients and Feasible for Residents to Participate?
AB  - Single-site robotic cholecystectomy (SSRC) accounts for most of the robotic
      surgery cases performed by general surgeons at our institution since acquiring
      the da Vinci Si Surgical SystemTM (Intuitive Surgical, Inc., Sunnyvale, CA) in
      2014. We sought to determine whether a SSRC program is safe to start in a public
      teaching hospital and to determine whether resident participation in this
      procedure is feasible. Data on age, gender, race, BMI, total operative time,
      length of stay, comorbidities, and conversion from laparoscopic to open surgery
      were examined for elective SSRC and laparoscopic cholecystectomies (LCs)
      performed by two faculty surgeons between February 2015 and August 2015. Thirty
      eight patients underwent elective SSRC, whereas 27 patients underwent LC.
      Residents participated as operating surgeons for some portion of the case in 15
      SSRC cases and in all LC cases. There were no significant differences in
      operative time, length of stay, or 30-day readmission rates, regardless of
      resident involvement. Patients in the SSRC group had a significantly lower BMI
      (25.8 vs 33.7, P = 0.008). This study suggests that resident participation does
      not increase complications or total operative time and that SSRC is a safe
      procedure to start in a public teaching hospital after proper faculty and
      resident training.

PMID- 29580345
TI  - Minimally Invasive versus Open Simultaneous Resections of Colorectal Cancer and
      Synchronous Liver Metastases: A Meta-Analysis.
AB  - The aim of this meta-analysis was to compare the efficacy and safety of
      simultaneous resections between the minimally invasive approach (MIA) and the
      open approach (OA) for patients with colorectal cancer (CRC) and synchronous
      colorectal liver metastases (SCRLM). A systematic search was conducted in the
      Cochrane Library, PubMed, EMBASE and Ovid databases (until May 5, 2016). Studies
      comparing the perioperative results and long-term outcomes for patients
      undergoing simultaneous CRC and SCRLM resections between the two approaches were
      evaluated. Six studies were identified, which included 164 minimally invasive and
      213 open simultaneous resections of CRC and SCRLM. MIA was associated with lesser
      surgical blood loss (mean difference = -155.85 mL; 95% confidence interval: 
      305.64 to -6.06, P = 0.04) and shorter length of postoperative stay (mean
      difference = -3.16 days; 95% confidence interval: -4.00 to -2.31, P < 0.00001.).
      The other perioperative results, including operating time, operative blood
      transfusion, intestinal function recovery time, and postoperative complications,
      did not differ significantly. No significant difference in the disease-free
      survival and overall survival rates between the two approaches was observed. In
      conclusion, compared with the OA, the MIA for simultaneous CRC and SCRLM
      resections is safe and effective for the treatment of SCRLM with lesser surgical
      blood loss and shorter length of postoperative stay. The MIA may be an
      alternative to the OA for simultaneous CRC and SCRLM resections for appropriately
      selected patients with resectable SCRLM.

PMID- 29580346
TI  - Head CT before Transfer Does Not Decrease Time to Craniotomy for TBI Patients.
AB  - Rural trauma education emphasizes that radiologic imaging should be discouraged
      if it delays transfer to definitive care. With increased capacity for image
      sharing, however, radiography obtained at referring hospitals (RH) could help
      providers at trauma centers (TC) prepare for patients with traumatic brain
      injury. We evaluated whether a head CT prior to transfer accelerated time to
      neurosurgical intervention at the TC. The study was conducted at a combined adult
      Level I and pediatric Level II TC with a catchment area that includes rural
      hospitals within a 150 mile radius. The trauma registry was used to identify
      patients with traumatic brain injury who went to surgery for a neurosurgical
      procedure immediately after arrival at the TC. All patients were transferred in
      from a RH. Differences between groups were assessed using analysis of variance
      and chi-square. Fifty-six patients met study criteria during the study period
      (2010-2015). The majority (86%) of patients received head CT imaging at the RH,
      including a significant percentage of patients (18%) who presented with GCS <=8.
      There was no statistically significant decrease in time to surgery when patients
      received imaging at the RH. CT imaging was associated with a delay in transfer
      that exceeded 90 minutes. Findings demonstrate that imaging at the RH delayed
      transfer to definitive care and did not improve time to neurosurgical
      intervention at the TC. Transfer to the TC should not be obstructed by imaging,
      especially for patients with severe TBI.

PMID- 29580347
TI  - Follow-Up Imaging in Patients with Blunt Splenic or Hepatic Injury Managed
      Nonoperatively.
AB  - Nonoperative management of blunt splenic and hepatic injuries has become the
      standard of care for hemodynamically stable patients. However, nonoperative
      management may lead to delayed complications and appropriate follow-up is
      therefore crucial. The aim of this systematic literature review was to assess the
      role of different imaging modalities in the follow-up assessment of patients with
      blunt splenic or hepatic injuries using the PubMed database. Eighteen studies
      were found to be relevant to the topic. A total of 2725 patients were enrolled in
      the included studies. Both retrospective and prospective studies, but no
      randomized controlled trials were found. In these studies, CT, ultrasound, and
      contrast-enhanced ultrasound were discussed. CT was the most commonly used
      imaging modality. Taking into account all studies included, only one patient
      underwent intervention due to a complication diagnosed by follow-up CT scan in
      the absence of clinical signs and symptoms. This equates to a total of 920 CT
      scans performed to diagnose one clinically nonevident complication that required
      intervention. Based on the reviewed literature, routine imaging follow-up CT
      scans may not be indicated in asymptomatic patients with lower grade blunt
      splenic or hepatic injuries. Contrast-enhanced ultrasound is a promising
      alternative imaging modality for the follow-up of these patients.

PMID- 29580348
TI  - Prosthetic Mesh Repair in the Emergency Management of Acutely Strangulated Groin
      Hernias with Grade I Bowel Necrosis: A Rational Choice.
AB  - The aim of this study was to determine the feasibility of prosthetic mesh repair
      according to the degree of bowel necrosis in the emergency management of acutely
      strangulated groin hernias. Emergency prosthetic mesh repair versus primary
      suture repair was randomly performed in 208 consecutive strangulated groin hernia
      patients with bowel necrosis between January 2005 and August 2016. The degree of
      bowel necrosis of each patient was determined according to a modified three-grade
      classification system. Patient characteristics sorted by repair method were
      analyzed by using Pearson's chi-squared tests. Correlations between mortality and
      wound-related morbidity with bowel necrosis grade and repair method were
      analyzed. There was no difference in gender, age, body mass index, comorbid
      diseases, hernia type (left or right, primary or recurrent), necrosis grade, and
      mortality between the mesh repair and suture repair groups (all P > 0.05).
      However, with regard to wound-related morbidity, there was significant difference
      between the two groups (P < 0.05). Mortality and wound-related morbidity showed
      significant relationship with necrosis grade, especially with regard to
      postoperative wound infection (P < 0.001). The wound infection rate with mesh
      repair was significantly higher than that with primary suture in Grade II and III
      necrosis patients (P < 0.05), but there was no difference in Grade I patients (P
      > 0.05). The use of prosthetic mesh in the emergency repair of acutely
      strangulated groin hernias seems to be as safe as suture-only repair in patients
      with noninfected strangulated bowel (Grade I necrosis). The use of prosthetic
      mesh repair is a rational choice made based on the degree of bowel necrosis in
      the emergency management of acutely strangulated hernias.

PMID- 29580349
TI  - eFAST for Pneumothorax: Real-Life Application in an Urban Level 1 Center by
      Trauma Team Members.
AB  - The focused assessment with sonography for trauma (FAST) examination has become
      the standard of care for rapid evaluation of trauma patients. Extended FAST
      (eFAST) is the use of ultrasonography for the detection of pneumothorax (PTX).
      The exact sensitivity and specificity of eFAST detecting traumatic PTX during
      practical "real-life" application is yet to be investigated. This is a
      retrospective review of all trauma patients with a diagnosis of PTX, who were
      treated at a large level 1 urban trauma center from March 2013 through July 2014.
      Charts were reviewed for results of imaging, which included eFAST, chest X-ray,
      and CT scan. The requirement of tube thoracostomy and mechanism of injury were
      also analyzed. A total of 369 patients with a diagnosis of PTX were identified. A
      total of 69 patients were excluded, as eFAST was either not performed or not
      documented, leaving 300 patients identified with PTX. A total of 113 patients had
      clinically significant PTX (37.6%), requiring immediate tube thoracostomy
      placement. eFAST yielded a positive diagnosis of PTX in 19 patients (16.8%), and
      all were clinically significant, requiring tube thoracostomy. Chest X-ray
      detected clinically significant PTX in 105 patients (92.9%). The literature on
      the utility of eFAST for PTX in trauma is variable. Our data show that although
      specific for clinically significant traumatic PTX, it has poor sensitivity when
      performed by clinicians with variable levels of ultrasound training. We conclude
      that CT is still the gold standard in detecting PTX, and clinicians performing
      eFAST should have adequate training.

PMID- 29580350
TI  - Frailty Predicts Morbidity after Colectomy for Ulcerative Colitis.
AB  - The rate of ulcerative colitis (UC), an inflammatory bowel disease, has been on
      the rise in the United States for the last several decades. Colectomy can be
      performed when other treatment options cannot provide a reasonable quality of
      life to patients with UC. Frailty has been shown to be a strong tool for
      evaluating preoperative risk factors for poor postoperative outcomes. The
      National Surgical Quality and Improvement Program cross-institutional database
      was used for this study. Data from 943 patients who underwent colectomy for UC
      between 2005 and 2012 were evaluated. Modified frailty index (mFI) is a
      previously described and validated 11-variable frailty measure used in the
      National Surgical Quality and Improvement Program to assess frailty. Outcome
      measures included serious morbidity; overall morbidity; cardiopulmonary, septic,
      and wound complications; and Clavien class IV (requiring ICU) and V (mortality)
      complications. Median age was 46 years and median body mass index was 25.5 Kg/m2.
      In all, 54.3 per cent of patients were male and 39.38 per cent of patients were
      American Society of Anesthesiologists Class lll or higher. The median mFI was 0
      (0-0.54). As the mFI increased from 0 (nonfrail) to 0.18 and above, the overall
      morbidity increased from 25.40 to 52.1 per cent (P < 0.05), serious morbidity
      increased from 14.9 to 42.1 per cent (P < 0.05), septic complications increased
      from 9.87 to 21.49 per cent (P < 0.05), cardiopulmonary complications increased
      from 2.98 to 23.14 per cent (P < 0.05), Clavien class IV complications increased
      from 3.5 to 26.5 per cent (P < 0.05), and Clavien V complications increased from
      0.16 to 6.61 per cent (P < 0.05). On multivariate analysis, mFI was an
      independent predictor of septic complications [Adjusted Odds Ratio (AOR): 31.26;
      P = 0.006], cardiopulmonary complications (AOR: 216.3; P <= 0.001), serious
      morbidity(AOR: 66.8; P <= 0.001), overall morbidity (AOR: 25.5; P <= 0.001),
      Clavien class IV (AOR: 204.9; P <= 0.001) complications, and return to the
      operating room (AOR: 14.29; P = 0.048). Frailty is associated with an increase in
      morbidity and mortality after colectomy in patients with UC. mFI is an easy-to
      use tool and can play an important role in the risk stratification of these
      patients.

PMID- 29580351
TI  - Short- and Long-Term Results of Laparoscopic Parenchyma-Sparing Hepatectomy for
      Small-Sized Hepatocellular Carcinoma: A Comparative Study Using Propensity Score
      Matching Analysis.
AB  - The aim of this study was to evaluate the degree of invasiveness and the clinical
      outcomes of laparoscopic parenchyma-sparing hepatectomy (LPSH) for a maximum
      hepatocellular carcinoma (HCC) size <=5 cm. Sixty-one LPSHs and 175 open
      parenchyma-sparing hepatectomies (OPSHs) for small-sized HCC were analyzed using
      a propensity score matching analysis. The median operative time was significantly
      shorter in the LPSH group (194 min) than in the OPSH group (275 minutes) (P <
      0.0001). The estimated blood loss was significantly lower in the LPSH group (100
      mL) than in the OPSH group (380 mL) (P < 0.0001). The incidences of superficial
      incisional surgical site infections and respiratory complications were
      significantly lower in the LPSH group than in the OPSH group (P = 0.0161 and
      0.0285, respectively). During the postoperative course, the white blood cell
      counts and C-reactive protein levels were significantly lower in the LPSH group.
      There were no differences in overall survival and disease-free survival (P =
      0.1293 and 0.4039, respectively), and no significant differences in terms of type
      of recurrence and site of intrahepatic recurrence (P = 0.1410). The data from the
      present series suggest the lesser invasiveness and safety of LPSH even for small
      sized HCC patients.

PMID- 29580352
TI  - Weight Loss and Glycemic Control after Sleeve Gastrectomy: Results from a Middle
      Eastern Center of Excellence.
AB  - Obesity and its associated metabolic disorders are strongly linked to both
      morbidity and mortality. Sleeve gastrectomy (SG) has been established as an
      effective means of weight loss for obese patients as well as a treatment for type
      2 diabetes mellitus (T2DM). This study was designed to examine the short- and
      midterm outcomes of patients who underwent SG in a Middle Eastern Center of
      Excellence, a military training teaching hospital. The clinical outcomes of 59
      patients with impaired glucose tolerance and T2DM who underwent SG between 2011
      and 2014 with at least one and up to four years of follow-up were studied. Data
      were collected and compared, including the pre- and post-surgery measures of
      weight, body mass index, glycosylated hemoglobin (HbA1c), and fasting blood
      glucose. Complete remission was defined as a fasting blood glucose level <=100
      mg/dL, an HbA1c <=6 mg/dL, without use of antidiabetic medications. All patients
      showed significant reduction in body mass index following SG. Tight glycemic
      control was achieved among both diabetic and prediabetic patients. In this study,
      88.14 per cent of all patients (diabetic and prediabetic) achieved complete
      resolution from their impaired glucose tolerance and T2DM and maintained normal
      blood glucose and HbA1C levels from one to four years postoperatively. SG is
      beneficial both in terms of short- and midterm weight loss and glucose control in
      both diabetic and prediabetic obese patients.

PMID- 29580353
TI  - When Hiring New Trauma and Surgical Critical Care Fellowship Graduates, What
      Qualities Are Most Desirable? A Survey of Trauma Directors and Trauma Program
      Administrators.
AB  - : A general surgeon shortage exists and fewer surgical residents specialize in
      trauma and surgical critical care (TSCC). We conducted a survey of trauma
      directors and administrators to determine what qualities are most desirable when
      hiring new TSCC fellowship graduates. METHODS: The survey, entitled "A Survey of
      Directors of Trauma on Hiring New Attending Trauma Surgeons," was submitted to
      the Eastern Association for the Surgery of Trauma (EAST) and distributed to the
      association members in January 2016. Categorical data were summarized using
      frequency counts and percentages. Comparisons of responses were analyzed using
      the chi-squared or Fisher's exact test. Statistical significance was denoted by P
      < 0.05. RESULTS: A total of 317 respondents from 1364 submitted surveys presented
      a response rate of 23.2 per cent. Of these respondents, 85.8 per cent (n = 272)
      decide whether or not a new trauma surgeon is hired and 33.7 per cent were trauma
      directors. In all, 82.9 per cent work at academic centers and have an
      Accreditation Council for Graduate Medical Education-approved general surgery
      residency and 58.4 per cent have an Accreditation Council for Graduate Medical
      Education-approved surgical critical care or acute care surgery fellowship. In
      total, 72.6 per cent work in American College of Surgeons-verified trauma centers
      and 45.0 per cent hire new trauma surgeons as needed. Of the 272 respondents who
      decide whether or not a new trauma surgeon is hired, the recommendation of the
      residency and fellowship program director is important. Word of mouth was the
      most important manner of finding a new hire and the most important qualities of a
      new TSCC physician were personality and likeability. CONCLUSION: The survey
      revealed that well-trained, likeable, enthusiastic, and personable TSCC
      physicians are the best candidates for hire.

PMID- 29580354
TI  - Prehospital Extrication Techniques: Neurological Outcomes Associated with the
      Rapid Extrication Method and the Kendrick Extrication Device.
AB  - Most emergency medical service personnel rely on one of two techniques to
      extricate motor vehicle crash victims; the Rapid Extrication Maneuver (REM) or
      the Kendrick Extrication Device (KED). The purpose of this study was to compare
      pre- and postextrication neurological outcomes between these two techniques. A
      retrospective review was conducted of all adult patients with a vertebral column
      injury resulting from motor vehicle collision and admitted to a Level I trauma
      center between January 1, 2003 and December 31, 2010. Standardized pre- and
      postextrication neurological examinations were reviewed for all patients. More
      than half of patients (N = 81) were extricated using the KED (53.1%, n = 43) and
      46.9 per cent (n = 38) were extricated with the REM. Except for the thoracic
      Abbreviated Injury Score, no differences between groups emerged related to the
      Glasgow Coma Scale score, Injury Severity Score or Abbreviated Injury Score.
      There were no pre- and postextrication changes for motor to all extremities and
      sensation to all extremities using either method. The results of this study
      suggest that the REM and the KED are equivalent in protecting the patient from
      neurologic injury after motor vehicle collision.

PMID- 29580355
TI  - A Cost-Benefit Analysis of Reducing Surgical Site Infections.
AB  - Surgical Site Infections (SSI) represent an onerous burden on our health-care
      system. This study was undertaken to determine the impact of a protocol aimed at
      reducing SSIs on the frequency and cost of SSIs after abdominal surgery.
      Beginning in 2013, 811 patients undergoing gastrointestinal operations were
      prospectively followed. In 2014, we initiated a protocol to reduce SSIs. SSIs
      were monitored before and after protocol implementation, and differences in SSI
      incidence and associated costs were determined. Before protocol initiation,
      standardized operative preparation cost was $40.85 to $126.94 per patient
      depending on the results of methicillin-resistant Staphylococcus aureus screen;
      after protocol initiation, the cost was $43.85 per patient, saving up to $83.09
      per patient. With the protocol in place, SSI rate was reduced from 4.9 to 3.4 per
      cent (13 of 379) representing a potential prevention of eight infections that
      would have cost payers $166,280 ($20,785 per infection). Notably, the SSI rate
      after pancreatectomy was reduced by 63 per cent (P = 0.04). With preparation and
      diligence, SSI rate can be meaningfully reduced and potential cost savings can be
      achieved. In particular, SSI rate reduction for major abdominal operations and
      especially pancreatic resections can be achieved. A protocol to reduce SSI is a
      "win-win" for all stakeholders and should be encouraged with thoughtful and
      active participation from all hospital disciplines.

PMID- 29580356
TI  - Substernal Goiter: Correlation between Grade and Surgical Approach.
AB  - Substernal goiter is defined as a thyroid growth beyond the thoracic inlet. Using
      the cross-section imaging CT system, it can be classified into three grades. The
      aim of the study was to validate the surgical approach and the occurrence of
      postoperative complications with substernal goiter extension in our patient
      population. From a total of 1145 patients who underwent thyroid surgery at our
      institution in a 15-year period, 60 patients with substernal goiter were
      included. Clinical features and demographics, degree of extension, surgical
      details, and complications were analyzed. Mean +/- SD age of the patients was 58
      +/- 14.7 years and 88 per cent were females. According to the cross-section
      imaging CT system 61.7 per cent were grade I, 23.3 per cent grade II, and 15 per
      cent grade III. Total thyroidectomy was performed in 78.3 per cent of the
      patients, subtotal thyroidectomy in 18.3 per cent, and lobectomy in 3.3 per cent.
      The cervical approach was sufficient to perform 96.7 per cent of the
      thyroidectomies, requiring partial sternotomy in only two patients with grade III
      substernal goiter. Patients with grade III substernal goiter had a higher risk
      for postoperative dysphonia (OR = 14.29, IC95% 1.14-178.9, P = 0.03), which
      occurred in three patients (two transient and one permanent). Transitory
      hypoparathyroidism was present in 20 patients (33.3%) and did not correlate with
      goiter extension. Most substernal goiters can be resected through a cervical
      approach, with relatively low morbidity. Postoperative dysphonia was directly
      related to the extension of the goiter. Few cases with grade III goiters require
      a partial sternotomy.

PMID- 29580357
TI  - Severe Bleeding in Pelvic Fractures: Considerations in Planning Damage Control.
AB  - Severe bleeding due to pelvic fractures may require damage control procedures,
      such as preperitoneal packing. In many cases, preperitoneal packing is performed
      without full abdominal exploration. There are concerns that such an approach may
      miss major iliac vascular injuries or other intraabdominal injuries. This
      analysis assessed the incidence of iliac vascular and intraabdominal injuries in
      patients with pelvic fractures. The National Trauma Data Bank was queried for
      blunt trauma patients. Patients with severe pelvic fractures were observed.
      Common or external iliac vascular lacerations (CEIVL) and associated
      intraabdominal injuries were recorded. The study comprised 42,122 patients with
      pelvic fractures, of which 3,221 (7.6%) were severe pelvic fractures. The
      incidence of CEIVL in patients with severe pelvic fractures was 10.7 per cent.
      Patient age greater than or equal to 65 years was an independent predictor of
      CEIVL. A total of 34.3 per cent of severe pelvic fracture patients had severe
      associated intraabdominal injuries, including injuries to the bladder (26.5%) and
      bowel (16.7%). Severe pelvic fractures are associated with a high incidence of
      iliac vascular and intraabdominal injuries. Preperitoneal pelvic packing without
      abdominal exploration may miss these injuries.

PMID- 29580358
TI  - Clinicopathological Features and Management of Appendiceal Mucoceles: A
      Systematic Review.
AB  - Appendiceal mucoceles (AMs) are rare mucin-containing neoplasms with malignant
      potential. Lack of evidence-based data exists defining clinicopathological
      features for management. MEDLINE search between 1995 and 2015 was performed using
      search criteria "Appendix mucocele." Systematic review of patient-, pathologic-,
      and treatment-related characteristics was performed and data analyzed. Among 276
      cases of non-perforated AMs, 163 (59%) patients were female, with variable and
      nonspecific presentation. Patients were treated with appendectomy (52.1%), right
      hemicolectomy (17.6%), partial cecectomy (17.2%), and ileocecetomy (13.1%).
      Pathologic evaluation revealed the following: cystadenoma/low-grade appendiceal
      mucinous neoplasm (54%), unspecified/benign (25%), retention cyst (14.1%),
      cystadenocarcinoma (4.2%), and mucosal hyperplasia (2.9%). All 11 (4.2%) patients
      with cystadenocarcinoma were female (P = 0.004), odds ratio for malignancy 1.07
      times higher for women. Synchronous colonic malignancy was reported in three
      patients (27%) with cystadenocarcinoma (P = 0.007), odds ratio of 12.1. AMs have
      low risk for malignancy. Treatment should begin with appendectomy-only and
      subsequently guided by pathologic diagnosis.

PMID- 29580359
TI  - Comparison of Transarterial Chemoembolization Combined with Radiofrequency
      Ablation Therapy versus Surgical Resection for Early Hepatocellular Carcinoma.
AB  - Both radiofrequency ablation (RFA) and surgical resection (SR) are radical
      treatment recommended for early hepatocellular carcinoma (HCC). Transarterial
      chemoembolization (TACE) is a palliative treatment for intermediate HCC, and
      TACE+RFA combined therapy is considered superior to TACE or RFA alone for
      management of early HCC. This systematic review compared the efficacy and safety
      of TACE+RFA combined therapy with SR for early HCC. Web of Science, PubMed,
      EMBASE, and the Cochrane Library were searched for literatures related with our
      topic. The primary endpoint was overall survival (OS), and the secondary endpoint
      was the recurrence-free survival (RFS) rate; safety was measured by the rate of
      major complications. The effect sizes of OS, RFS, and local progression rates
      were expressed by odds ratio (OR), while the effect size of complications was
      presented using relative risk. TACE+RFA combined therapy and SR had a similar 1
      year OS rate [OR: 1.84; 95% confidence interval (CI): 0.82, 4.14; P > 0.05], 3
      year OS rate (OR: 0.84; 95% CI: 0.43, 1.67; P > 0.05), 1-year RFS rate (OR: 0.77;
      95% CI: 0.53, 1.11; P > 0.05), and 3-year RFS rate (OR: 0.88; 95% CI: 0.48, 1.42;
      P > 0.05) for early HCC. However, the 5-year OS rate (OR: 0.54; 95% CI: 0.40,
      0.73; P < 0.05) and 5-year RFS rate (OR: 0.49; 95% CI: 0.27, 0.90; P < 0.05) were
      lower in patients with TACE+RFA than in those with SR. SR is associated with
      better long-term survival outcomes and a lower recurrence rate than TACE+RFA for
      patients with early HCC and is the optimal choice for patients with early HCC.

PMID- 29580360
TI  - Helmets Matter: Kentucky All-Terrain Vehicle Crashes Seen at a Tennessee Trauma
      Center.
AB  - All-terrain vehicle (ATV) safety laws, including helmet use, vary by state and
      are sporadically enforced. Kentucky state laws require safety helmets only for
      younger riders. We hypothesized that ATV riders injured in Kentucky and seen at a
      Tennessee trauma center would more likely be unhelmeted, have more severe head
      injuries, and have higher mortality rates than those injured in Virginia or
      Tennessee. A Trauma Registry review of 750 injured ATV riders from June 1, 2005,
      through June 1, 2015 examined state location of accident, helmet use, markers of
      injury severity, and outcomes. Multiple logistic regression analysis examined
      predictors of severe head injuries and death with P < 0.05 significant.
      Unhelmeted ATV rider status predicted more severe head injuries (relative risk
      23.5, P < 0.001) and death (relative risk 4.6, P < 0.001). ATV riders injured in
      the state of Kentucky were twice as numerous. In addition, they were more likely
      than ATV riders injured in Tennessee or Virginia to be unhelmeted, to have severe
      head injuries, and to sustain fatal injuries (all P < 0.001). This single trauma
      center study lends support for maintaining and enforcing current universal helmet
      laws for ATV riders of all ages in states where they are in effect and highlights
      the need to upgrade helmet laws that apply only to some riders.

PMID- 29580361
TI  - Supervisor, Colleague, or Assistant: General Surgery Resident Perceptions of
      Advanced Practitioners.
AB  - Integration of advanced practitioners (APs) into academic medical centers can
      improve processes of care and decrease physician workload but may adversely
      impact general surgery residency training. The aim of the present study was to
      characterize general surgery resident perceptions of APs and their impact on
      resident training. We conducted an institutional review board-approved survey
      covering five topic areas: knowledge of AP training, interaction with APs, scope
      of-practice of APs, role of APs in the health-care team, and impact of APs on
      physician training. The survey was administered to general surgery residents at
      six large academic medical centers. One hundred eighteen general surgery
      residents completed the survey. The majority (43.6%) of respondents were junior
      residents. All respondents had interactions with APs with 90.7 per cent having
      worked directly with an AP in the last month. Residents reported minimal formal
      educational involvement by APs with 6.8 per cent reporting participation in
      didactics and 22.2 per cent teaching operative techniques. Almost half (44.1%) of
      the respondents reported that APs played an important role in their education,
      and 42.4 per cent of respondents disagreed or strongly disagreed that the role of
      the AP is well defined in their hospital. Today's general surgery residents work
      closely with APs who seem to positively impact resident education. Although
      residents perceive significant benefit with integration of APs, well-defined
      roles are lacking.

PMID- 29580362
TI  - Inadequacy of Algorithmic Ventilator-Associated Pneumonia Diagnosis in Acute Care
      Surgery.
AB  - Clinical utility of algorithms to diagnose ventilator-associated pneumonia (VAP)
      in surgical patients has not been established. We aimed to test the diagnostic
      accuracy of two established methods to reliably diagnose VAP in acutely ill and
      injured surgical patients. After institutional review board approval, we
      prospectively collected data on 508 mechanically ventilated acute care surgery
      patients. Microbiologic samples were taken daily from all patients. Demographics,
      clinical, laboratory, and radiographic data were collected. The Johanson Criteria
      (JC) and Clinical Pulmonary Infection Score (CPIS) were calculated and analyzed.
      Sensitivity, specificity, and positive predictive values (PPV) and negative
      predictive value (NPV) were calculated in comparison to positive respiratory
      cultures. Of the 508 patients, 312 (61.4%) were acutely injured; emergent general
      surgery was performed in 141 (27.8%) patients, and 54 (10.6%) underwent elective
      operation. Positive respiratory cultures were identified in 198 (39%) of the 508
      patients. JC diagnosed VAP in 291 (57.3%) patients (sensitivity 82.8%,
      specificity 59%, PPV 56.4%, NPV 84.3%, accuracy 68.3%). The CPIS resulted in 189
      (37.2%) VAP diagnoses (sensitivity 61.1%, specificity 78.1%, PPV 64%, NPV 75.9%,
      and accuracy 71.5%). To address the inaccuracy of the algorithms, concordance
      testing was performed on the data to evaluate correlation between the algorithmic
      VAP diagnosis criteria and respiratory culture data. Nonconcordance with culture
      data diagnosis was identified with both JC (rho 0.41) and CPIS (rho 0.41).
      Sensitivity, specificity, PPV and NPV, and accuracy of both established clinical
      formulas was unacceptably low in acute care surgery patients.

PMID- 29580363
TI  - Prospective Analysis of Epigastric, Umbilical, and Small Incisional Hernia Repair
      Using the Modified Kugel Oval Patch.
AB  - The study was performed to determine the complication and recurrence rate using
      the modified Kugel oval patch for small ventral hernia repair. Another aim of the
      study was to find risk factors for recurrence in patients with this repair.
      Seventy-three patients underwent ventral hernia repair with the modified Kugel
      oval patch between April 2013 and February 2015. Prospective follow-up data (18
      months postoperative) were collected and evaluated. A total of 58 primary (18
      epigastric/40 umbilical) and 15 incisional ventral hernias were repaired with the
      modified Kugel oval patch (7.6/10.2 cm/8 * 12 cm). We found three patients
      suffered superficial wound infection and two participants got hernia recurrence.
      Placement of mesh was found to be a significant risk factor for hernia
      recurrence. Small ventral hernia repair using the modified Kugel oval patch is a
      novel and useful approach and we recommend placing the patch preperitoneally.

PMID- 29580365
TI  - A Case of Non-Obstructive Afferent Loop Syndrome after Roux-en-Y Gastric Bypass.

PMID- 29580364
TI  - Statewide Analysis Shows Collaborative Regional Trauma Network Reduces Regional
      Mortality.
AB  - A Regional Trauma Network (RTN), composed of one level I and several lower-level
      trauma centers (TCs) across multiple hospital systems, was established in 2010.
      This collaborative network used a unified triage protocol and a single transfer
      center. The impact of this RTN was assessed by evaluating regional mortality
      changes before and after RTN establishment. Patients in the state trauma registry
      aged 15 and older from 2006 to 2012 were analyzed; 2006 to 2009 and 2010 to 2012
      were designated as pre-RTN and RTN periods, respectively. The region was defined
      as a county containing L1TC and its adjacent counties. Any counties bordering
      multiple L1TC-containing counties were excluded from analysis. Mortality was
      compared for all regions before and after RTN implementation. The following
      subgroups were also included a priori for the comparison: Injury Severity Score
      >=15, age >=65, and trauma mechanisms. 121,448 patients were analyzed; 66,977 and
      54,471 patients were in the pre-RTN and RTN groups, respectively. Mean age was
      58; 90 per cent had blunt injuries. The overall mortality was 4.9 per cent.
      Mortality comparisons over time for all regions are presented. The RTN region was
      the only region in the state that had mortality reduction in all patient
      subgroups. After adjusting for age, Injury Severity Score, level of TC that
      performed treatment, and trauma mechanism, RTN implementation was an independent
      predictor of survival (odds ratio: 0.876; 95% CI: 0.771-0.995, P = 0.04, c
      statistic: 0.84). These findings suggest that regional collaboration and network
      wide, uniform triage practices should be key components in the development of
      regionalized trauma networks.

PMID- 29580366
TI  - Mixed Adenoneuroendocrine Carcinoma (MANEC) of the Distal Common Bile Duct
      Arising from a Choledochal Cyst.

PMID- 29580367
TI  - Comparison of the Cepheid Xpert HPV test and the HC2 High-Risk HPV DNA Test for
      detection of high-risk HPV infection in cervical smear samples in SurePath
      preservative fluid.
AB  - PURPOSE: Cytological and histological cervical screening methods for human
      papillomavirus may be subjective. Current guidelines recommend the use of direct
      human papillomavirus screening by molecular methods in conjunction with cytology
      for the detection of high-risk human papillomavirus types with carcinogenic
      potential. In this study, we compared the performance of the molecular Cepheid
      Xpert HPV test to the FDA-approved HC2 High-Risk HPV DNA Test on samples from
      patients presenting for cervical screening, regardless of the cytology results,
      in which cervical cell samples were originally collected for Papanicolaou (Pap)
      smear specimens in Becton Dickinson (BD) SurePath preservative fluid.
      METHODOLOGY: Cervical cells were obtained for Pap smear specimens from 343 women
      attending Qatif Central Hospital in Saudi Arabia for cervical cancer screening
      using a Cytobrush Plus GT and immersed in BD SurePath preservative fluid in BD
      SurePath collection vials. The study was carried out between December 2015 and
      July 2016. RESULTS: The Xpert HPV test was positive in 27 (7.9 %) of the samples.
      The HC2 High-Risk HPV DNA Test was positive in 32 (9.3 %) of the samples. The
      most common HPV types according to the Xpert HPV test were HPV other types,
      either alone (n=15) or in combination with HPV16 (n=3). The overall concordance
      rate between the tests was 98.5 %. The positive concordance was 84.4 %.
      CONCLUSION: The Xpert HPV test is convenient to use on cervical cell samples
      collected for Pap smear specimens in BD SurePath preservative fluid within an
      hour and is a viable alternative to the HC2 High-Risk HPV DNA Test for HPV
      testing.

PMID- 29580368
TI  - Anaerobacillus isosaccharinicus sp. nov., an alkaliphilic bacterium which
      degrades isosaccharinic acid.
AB  - Strain NB2006T was isolated from an isosaccharinate-degrading, nitrate-reducing
      enrichment culture in minimal freshwater medium at pH 10. Analysis of the 16S
      rRNA gene sequence indicated that this strain was most closely related to species
      of the newly established genus Anaerobacillus. This was supported by phenotypic
      and metabolic characterisation that showed that NB2006T was rod-shaped, Gram
      stain-positive, motile and formed endospores. It was an aerotolerant anaerobe and
      an obligate alkaliphile that grew at pH 8.5-11, could tolerate up to 6 % (w/v)
      NaCl, and grew at a temperature between 10 and 40  degrees C. In addition, it
      could utilise a number of organic substrates, and was able to reduce nitrate and
      arsenate. The predominant cellular fatty acids were C16 : 0, C16 : 1omega11c,
      anteiso-C15 : 0, iso-C15 : 0, C16 : 1omega7c/iso-C15 : 0 2-OH and C14 : 0. The
      cell wall peptidoglycan contained meso-diaminopimelic acid and the DNA G+C
      content was 37.7 mol%. In silico DNA-DNA hybridization with the four known
      species of the genus Anaerobacillus showed 21.8, 21.9, 22.4, and 21.5 %
      relatedness to Anaerobacillusarseniciselenatis DSM 15340T, Anaerobacilus
      alkalidiazotrophicus DSM 22531T, Anaerobacillusalkalilacustris DSM 18345T, and
      Anaerobacillus macyae DSM 16346T, respectively. NB2006T differed from strains of
      other species of the genus Anaerobacillus in its ability to metabolise
      isosaccharinate, an alkaline hydrolysis product of cellulose. On the basis of the
      consensus of phylogenetic and phenotypic analyses, this strain represents a novel
      species of the genus Anaerobacillus, for which the name Anaerobacillus
      isosaccharinicus sp. nov. is proposed. The type strain is NB2006T (=DSM
      100644T=LMG 30032T).

PMID- 29580369
TI  - Mechanism of activation of the BNLF2a immune evasion gene of Epstein-Barr virus
      by Zta.
AB  - The human gamma herpes virus Epstein-Barr virus (EBV) exploits multiple routes to
      evade the cellular immune response. During the EBV lytic replication cycle, viral
      proteins are expressed that provide excellent targets for recognition by
      cytotoxic T cells. This is countered by the viral BNLF2a gene. In B cells during
      latency, where BNLF2a is not expressed, we show that its regulatory region is
      embedded in repressive chromatin. The expression of BNLF2a mirrors the expression
      of a viral lytic cycle transcriptional regulator, Zta (BZLF1, EB1, ZEBRA), in B
      cells and we propose that Zta plays a role in up-regulating BNLF2a. In cells
      undergoing EBV lytic replication, we identified two distinct regions of
      interaction of Zta with the chromatin-associated BNLF2a promoter. We identify
      five potential Zta-response elements (ZREs) in the promoter that are highly
      conserved between virus isolates. Zta binds to these elements in vitro and
      activates the expression of the BNLF2a promoter in both epithelial and B cells.
      We also found redundancy amongst the ZREs. The EBV genome undergoes a biphasic
      DNA methylation cycle during its infection cycle. One of the ZREs contains an
      integral CpG motif. We show that this can be DNA methylated during EBV latency
      and that both Zta binding and promoter activation are enhanced by its
      methylation. In summary, we find that the BNLF2a promoter is directly targeted by
      Zta and that DNA methylation within the proximal ZRE aids activation. The
      implications for regulation of this key viral gene during the reactivation of EBV
      from latency are discussed.

PMID- 29580370
TI  - Identification of a newly described OsHV-1 uvar from the North Adriatic Sea
      (Italy).
AB  - The surveillance activities for abnormal bivalve mortality events in Italy
      include the diagnosis of ostreid herpesvirus type 1 (OsHV-1) in symptomatic
      oysters. OsHV-1-positive oysters (Crassostrea gigas) were used as a source for in
      vivo virus propagation and a virus-rich sample was selected to perform shotgun
      sequencing based on Illumina technology. Starting from this unpurified
      supernatant sample from gills and mantle, we generated 3.5 million reads (2*300
      bp) and de novo assembled the whole genome of an Italian OsHV-1 microvariant
      (OsHV-1-PT). The OsHV-1-PT genome encodes 125 putative ORFs, 7 of which had not
      previously been predicted in other sequenced Malacoherpesviridae. Overall, OsHV-1
      PT displays typical microvariant OsHV-1 genome features, while few polymorphisms
      (0.08 %) determine its uniqueness. As little is known about the genetic
      determinants of OsHV-1 virulence, comparing complete OsHV-1 genomes supports a
      better understanding of the virus pathogenicity and provides new insights into
      virus-host interactions.

PMID- 29580371
TI  - Small RNA Esr41 inversely regulates expression of LEE and flagellar genes in
      enterohaemorrhagic Escherichia coli.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) is a life-threatening human pathogen
      worldwide. The locus of enterocyte effacement (LEE) in EHEC encodes a type three
      secretion system and effector proteins, all of which are essential for bacterial
      adherence to host cells. When LEE expression is activated, flagellar gene
      expression is down-regulated because bacterial flagella induce the immune
      responses of host cells at the infection stage. Therefore, this inverse
      regulation is also important for EHEC infection. We report here that a small
      regulatory RNA (sRNA), Esr41, mediates LEE repression and flagellar gene
      activation. Multiple copies of esr41 abolished LEE expression by down-regulating
      the expression of ler and pch, which encode positive regulators of LEE. This
      regulation led to reduced EHEC adhesion to host cells. Translational gene
      reporter fusion experiments revealed that Esr41 regulates ler expression at a
      post-transcriptional level, and pch transcription, probably via an unknown target
      of Esr41. Esr41-mediated ler and pch repression was not observed in cells lacking
      hfq, which encodes an RNA-binding protein essential for most sRNA functions,
      indicating that Esr41 acts in an Hfq-dependent manner. We previously reported an
      increase in cell motility induced by Esr41. This motility enhancement was also
      observed in EHEC lacking ler, showing that Esr41-mediated enhancement of cell
      motility is in a ler-independent manner. In addition, Esr41 activated the
      expression of flagellar Class 3 genes by indirectly inducing the transcription of
      fliA, which encodes the sigma factor for flagellar synthesis. These results
      suggest that Esr41 plays important roles in the inverse regulation of LEE and
      flagellar gene expression.

PMID- 29580372
TI  - Neptunicoccus sediminis gen. nov., sp. nov., a member of the family
      Rhodobacteraceae isolated from the Yellow Sea.
AB  - A novel Gram-stain-negative bacterium, designated strain CY02T, was isolated from
      sediment of the Yellow Sea. Cells of CY02T were aerobic, coccus or short rods.
      Growth occurred at 5-42  degrees C (optimum, 35  degrees C), pH 6-10 (optimum,
      8.0) and 0.5-9.0 % NaCl (optimum, 1.5-3.0 %). Phylogenetic analysis of 16S rRNA
      gene sequences revealed that CY02T was a member of the family Rhodobacteraceae
      and exhibited less than 95 % sequence similarities with the closely related type
      strains of the family Rhodobacteraceae. The genomic DNA G+C content of CY02T was
      57.5 mol%. The major respiratory quinone was ubiquinone-10 (Q-10). The polar
      lipids consisted of phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, diphosphatidylglycerol, three unidentified lipids, one
      unidentified phospholipid and one unidentified aminolipid. The predominant
      cellular fatty acids were C18 : 1omega7c (57.6 %), 11-methyl C18 : 1omega7c (22.8
      %) and C16 : 0 (10.6 %). Based on the results of morphological, physiological,
      biochemical, chemotaxonomic, genotypic and phylogenetic analyses, strain CY02T
      represents a novel species of a novel genus of the family Rhodobacteraceae, for
      which the name Neptunicoccus sediminis gen. nov., sp. nov. is proposed. The type
      strain of Neptunicoccus sediminis is CY02T (=CCTCC AB 2015430T=KCTC 42985T=NBRC
      111872T=MCCC 1K03518).

PMID- 29580373
TI  - Comparative analysis of prions in nervous and lymphoid tissues of chronic wasting
      disease-infected cervids.
AB  - The prevalence, host range and geographical bounds of chronic wasting disease
      (CWD), the prion disease of cervids, are expanding. Horizontal transmission
      likely contributes the majority of new CWD cases, but the mechanism by which
      prions are transmitted among CWD-affected cervids remains unclear. To address the
      extent to which prion amplification in peripheral tissues contributes to
      contagious transmission, we assessed the prion levels in central nervous and
      lymphoreticular system tissues in white-tailed deer (Odocoileus virginianus), red
      deer (Cervus elaphus elaphus) and elk (Cervus canadensis). Using real-time
      quaking-induced conversion, cervid prion cell assay and transgenic mouse
      bioassay, we found that the retropharyngeal lymph nodes of red deer, white-tailed
      deer and elk contained similar prion titres to brain from the same individuals.
      We propose that marked lymphotropism is essential for the horizontal transmission
      of prion diseases and postulate that shed CWD prions are produced in the
      periphery.

PMID- 29580374
TI  - Mitochondrial dysfunction suppresses p53 expression via calcium-mediated nuclear
      factor-kB signaling in HCT116 human colorectal carcinoma cells.
AB  - Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types.
      Although the correlation between mitochondrial dysfunction and cancer malignancy
      has been demonstrated by several studies, further research is required to
      elucidate the molecular mechanisms underlying accelerated tumor development and
      progression due to mitochondrial mutations. We generated an mtDNA-depleted cell
      line, rho0, via long-term ethidium bromide treatment to define the molecular
      mechanisms of tumor malignancy induced by mitochondrial dysfunction.
      Mitochondrial dysfunction in rho0 cells reduced drug-induced cell death and
      decreased the expression of pro-apoptotic proteins including p53. The p53
      expression was reduced by activation of nuclear factor-kappaB that depended on
      elevated levels of free calcium in HCT116/rho0 cells. Overall, these data provide
      a novel mechanism for tumor development and drug resistance due to mitochondrial
      dysfunction. [BMB Reports 2018; 51(6): 296-301].

PMID- 29580375
TI  - Photoperiod sensing system for timing of flowering in plants.
AB  - CONSTANS (CO) induces the expression of FLOWERING LOCUS T (FT) in the
      photoperiodic pathway, and thereby regulates the seasonal timing of flowering. CO
      expression is induced and CO protein is stabilized by FLAVIN-BINDING KELCH REPEAT
      F-BOX PROTEIN 1 (FKF1) in the late afternoon, while CO is degraded by
      CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) during the night. These regulatory
      cascades were thought to act independently. In our study, we investigated the
      relationship between FKF1 and COP1 in the regulation of CO stability in response
      to ambient light conditions. A genetic analysis revealed that FKF1 acts as a
      direct upstream negative regulator of COP1, in which cop1 mutation is epistatic
      to fkf1 mutation in the photoperiodic regulation of flowering. COP1 activity
      requires the formation of a hetero-tetramer with SUPPRESSOR OF PHYA-105 (SPA1),
      [(COP1)2(SPA1)2]. Light-activated FKF1 has an increased binding capacity for
      COP1, forming a FKF1-COP1 hetero-dimer, and inhibiting COP1 homo-dimerization at
      its coiled-coil (CC) domain. Mutations in the CC domain result in poor COP1
      dimerization and misregulation of photoperiodic floral induction. We propose that
      FKF1 represses COP1 activity by inhibiting COP1 dimerization in the late
      afternoon under long-day conditions, resulting in early flowering. [BMB Reports
      2018; 51(4): 163-164].

PMID- 29580376
TI  - High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD
      negative women not known to be sensitised to the RhD antigen: a systematic review
      and economic evaluation.
AB  - BACKGROUND: High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus
      (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D
      immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although
      this may lead to an increased risk of RhD sensitisations. OBJECTIVES: To
      systematically review the evidence on the diagnostic accuracy, clinical
      effectiveness and implementation of high-throughput NIPT and to develop a cost
      effectiveness model. METHODS: We searched MEDLINE and other databases, from
      inception to February 2016, for studies of high-throughput NIPT free-cell fetal
      deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD
      status in RhD-negative pregnant women who were not known to be sensitised to the
      RhD antigen. Study quality was assessed with the Quality Assessment of Diagnostic
      Accuracy Studies 2 (QUADAS-2) and A Cochrane Risk of Bias Assessment Tool: for
      Non-Randomised Studies of Interventions (ACROBAT-NRSI). Summary estimates of
      false-positive rates (FPRs) and false-negative rates (FNRs) were calculated using
      bivariate models. Clinical effectiveness evidence was used to conduct a
      simulation study. We developed a de novo probabilistic decision tree-based cohort
      model that considered four alternative ways in which the results of NIPT could
      guide the use of anti-D immunoglobulin antenatally and post partum. Sensitivity
      analyses (SAs) were conducted to address key uncertainties and model assumptions.
      RESULTS: Eight studies were included in the diagnostic accuracy review, seven
      studies were included in the clinical effectiveness review and 12 studies were
      included in the review of implementation. Meta-analyses included women mostly at
      or post 11 weeks' gestation. The pooled FNR (women at risk of sensitisation) was
      0.34% [95% confidence interval (CI) 0.15% to 0.76%] and the pooled FPR (women
      needlessly receiving anti-D) was 3.86% (95% CI 2.54% to 5.82%). SAs did not
      materially alter the overall results. Data on clinical outcomes, including
      sensitisation rates, were limited. Our simulation suggests that NIPT could
      substantially reduce unnecessary use of antenatal anti-D with only a small
      increase in the risk of sensitisation. All large implementation studies suggested
      that large-scale implementation of high-throughput NIPT was feasible. Seven cost
      effectiveness studies were included in the review, which found that the potential
      for the use of NIPT to produce cost savings was dependent on the cost of the
      test. Our de novo model suggested that high-throughput NIPT is likely to be cost
      saving compared with the current practice of providing routine antenatal anti-D
      prophylaxis to all women who are RhD negative. The extent of the cost saving
      appeared to be sufficient to outweigh the small increase in sensitisations.
      However, the magnitude of the cost saving is highly sensitive to the cost of NIPT
      itself. LIMITATIONS: There was very limited evidence relating to the clinical
      effectiveness of high-throughput NIPT, with no evidence on potential adverse
      effects. The generalisability of the findings to non-white women and multiple
      pregnancies is unclear. CONCLUSIONS: High-throughput NIPT is sufficiently
      accurate to detect fetal RhD status in RhD-negative women from 11 weeks'
      gestation and would considerably reduce unnecessary treatment with routine anti-D
      immunoglobulin, potentially resulting in cost savings of between L485,000 and
      L671,000 per 100,000 pregnancies if the cost of implementing NIPT is in line with
      that reflected in this evaluation. FUTURE WORK: Further research on the
      diagnostic accuracy of NIPT in non-white women is needed. STUDY REGISTRATION:
      This study is registered as PROSPERO CRD42015029497. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 29580377
TI  - Chemsex among men who have sex with men in Germany: motives, consequences and the
      response of the support system.
AB  - : Background In Germany, drug use in sexual settings (i.e. chemsex) among men who
      have sex with men (MSM) has increasingly been the subject of discussion for
      considerable time. At the same time, however, little is known about this
      practice. It is against this background that what is currently known about
      chemsex among MSM in Germany is discussed. METHODS: The present study
      observations are essentially based on the results of two research projects of a
      qualitative-explorative nature. In-depth interviews with drug-using MSM (n=14),
      as well as qualitative, problem-centred interviews with drug-using MSM (n=75) and
      expert interviews (n=27) were conducted within these research projects. RESULTS:
      Chemsex is a minority behaviour among MSM in Germany. The reasons for using drugs
      in sexual settings are manifold. For the most part, the effects of the drugs are
      used to intensify sexual feelings and to achieve greater intimacy. Men who
      consider their consumption to be problematic, in particular, report a range of
      negative consequences, such as sexually transmissible infections. Even though
      chemsex is a minority behaviour, suitable offers of support are, hence,
      necessary, especially for these men. However, such offers are not yet available
      in most German cities. CONCLUSIONS: In order to close this gap in provision of
      support services, tangible practical steps, such as further training of people
      who work at drug and gay advisory services, are necessary, along with further
      research into the backgrounds and contexts of chemsex.

PMID- 29580378
TI  - Hypoexcitability precedes denervation in the large fast-contracting motor units
      in two unrelated mouse models of ALS.
AB  - Hyperexcitability has been suggested to contribute to motoneuron degeneration in
      amyotrophic lateral sclerosis (ALS). If this is so, and given that the
      physiological type of a motor unit determines the relative susceptibility of its
      motoneuron in ALS, then one would expect the most vulnerable motoneurons to
      display the strongest hyperexcitability prior to their degeneration, whereas the
      less vulnerable should display a moderate hyperexcitability, if any. We tested
      this hypothesis in vivo in two unrelated ALS mouse models by correlating the
      electrical properties of motoneurons with their physiological types, identified
      based on their motor unit contractile properties. We found that, far from being
      hyperexcitable, the most vulnerable motoneurons become unable to fire
      repetitively despite the fact that their neuromuscular junctions were still
      functional. Disease markers confirm that this loss of function is an early sign
      of degeneration. Our results indicate that intrinsic hyperexcitability is
      unlikely to be the cause of motoneuron degeneration.

PMID- 29580379
TI  - Single-cell RNA-seq reveals hidden transcriptional variation in malaria
      parasites.
AB  - Single-cell RNA-sequencing is revolutionising our understanding of seemingly
      homogeneous cell populations but has not yet been widely applied to single-celled
      organisms. Transcriptional variation in unicellular malaria parasites from the
      Plasmodium genus is associated with critical phenotypes including red blood cell
      invasion and immune evasion, yet transcriptional variation at an individual
      parasite level has not been examined in depth. Here, we describe the adaptation
      of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute
      transcriptional variation for more than 500 individual parasites of both rodent
      and human malaria comprising asexual and sexual life-cycle stages. We uncover
      previously hidden discrete transcriptional signatures during the pathogenic part
      of the life cycle, suggesting that expression over development is not as
      continuous as commonly thought. In transmission stages, we find novel, sex
      specific roles for differential expression of contingency gene families that are
      usually associated with immune evasion and pathogenesis.

PMID- 29580380
TI  - Resilience of small intestinal beneficial bacteria to the toxicity of soybean oil
      fatty acids.
AB  - Over the past century, soybean oil (SBO) consumption in the United States
      increased dramatically. The main SBO fatty acid, linoleic acid (18:2), inhibits
      in vitro the growth of lactobacilli, beneficial members of the small intestinal
      microbiota. Human-associated lactobacilli have declined in prevalence in Western
      microbiomes, but how dietary changes may have impacted their ecology is unclear.
      Here, we compared the in vitro and in vivo effects of 18:2 on Lactobacillus
      reuteri and L. johnsonii. Directed evolution in vitro in both species led to
      strong 18:2 resistance with mutations in genes for lipid biosynthesis, acid
      stress, and the cell membrane or wall. Small-intestinal Lactobacillus populations
      in mice were unaffected by chronic and acute 18:2 exposure, yet harbored both
      18:2- sensitive and resistant strains. This work shows that extant small
      intestinal lactobacilli are protected from toxic dietary components via the gut
      environment as well as their own capacity to evolve resistance.

PMID- 29580381
TI  - Origin and evolution of the nuclear auxin response system.
AB  - The small signaling molecule auxin controls numerous developmental processes in
      land plants, acting mostly by regulating gene expression. Auxin response proteins
      are represented by large families of diverse functions, but neither their origin
      nor their evolution is understood. Here, we use a deep phylogenomics approach to
      reconstruct both the origin and the evolutionary trajectory of all nuclear auxin
      response protein families. We found that, while all subdomains are ancient, a
      complete auxin response mechanism is limited to land plants. Functional
      phylogenomics predicts defined steps in the evolution of response system
      properties, and comparative transcriptomics across six ancient lineages revealed
      how these innovations shaped a sophisticated response mechanism. Genetic analysis
      in a basal land plant revealed unexpected contributions of ancient non-canonical
      proteins in auxin response as well as auxin-unrelated function of core
      transcription factors. Our study provides a functional evolutionary framework for
      understanding diverse functions of the auxin signal.

PMID- 29580382
TI  - High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1
      dependent phosphorylation of Cdc28CDK1.
AB  - Whole-genome duplications (WGDs) have played a central role in the evolution of
      genomes and constitute an important source of genome instability in cancer. Here,
      we show in Saccharomyces cerevisiae that abnormal accumulations of histones are
      sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation
      of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of
      histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation
      and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA
      damage response. Our results link high levels of histones to a specific type of
      genome instability that is quite frequently observed in cancer and uncovers a new
      mechanism that might be able to respond to high levels of histones.

PMID- 29580383
TI  - Cherub versus brat.
AB  - A long non-coding RNA molecule called cherub is a driver of tumor development.

PMID- 29580385
TI  - Synergistic effect of kappa-carrageenan and gelatin blends towards adipose tissue
      engineering.
AB  - The current paper focuses on the functionalization of kappa-carrageenan and
      gelatin as extracellular matrix polysaccharide and protein mimic respectively to
      produce hydrogel films for adipose tissue engineering. More specifically, kappa
      carrageenan as well as gelatin have been functionalized with methacrylate and
      methacrylamide moieties respectively to enable subsequent UV-induced crosslinking
      in the presence of a photo-initiator. The gel fraction, the mass swelling ratio
      and the mechanical properties of both the one-component hydrogels and the
      protein/polysaccharide blends have been evaluated. The mechanical and swelling
      properties of the blends could be tuned by varying the hydrogel composition as
      well as the crosslinking method applied. The in vitro biocompatibility assays
      indicated a significantly higher cell viability of adipose tissue-derived
      mesenchymal stem cells seeded onto the blends as compared to the one-component
      hydrogels. The results show that the blends of gelatin and kappa-carrageenan
      clearly outperform the one-component hydrogels in terms of adipose tissue
      engineering potential.

PMID- 29580386
TI  - Two structurally similar fucosylated chondroitin sulfates from the holothurian
      species Stichopus chloronotus and Stichopus horrens.
AB  - Two fucosylated chondroitin sulfates SC and SH were isolated from the holothurian
      species Stichopus chloronotus and Stichopus horrens, respectively. The molar
      ratio of monosaccharides and sulfate (GalNAc:GlcA:Fuc:SO3Na) was suggested as
      ~1:1:1:4 for both polysaccharides. Really this theoretical ratio was slightly
      distorted by the presence of some fucan sulfate in both preparations (about 2% in
      SH and 10% in SC), which could not be separated probably due to coincidence with
      the main components in charge density and molecular weight. The 1D and 2D NMR
      spectroscopic methods were applied for the detailed structural characterization
      of SC and SH, which were found to have similar structures. The main chain of SC
      and SH was shown to be composed of the repeating disaccharide units ->4)-beta-d
      GlcA-(1 -> 3)-beta-d-GalNAc-(1-> sulfated at O-4 or both at O-4 and O-6 of the N
      acetyl-galactosaminyl residues. The ratio of mono- and disulfated GalNAc residues
      was determined as 1:9 for SC and SH. Only one type of branches linked to O-3 of
      glucuronyl residues, namely fucosyl 2,4-disulfate residues, were found in both
      polysaccharides. Therefore polysaccharides SC and SH are two new examples of
      highly regular fucosylated chondroitin sulfates.

PMID- 29580384
TI  - The asymmetrically segregating lncRNA cherub is required for transforming stem
      cells into malignant cells.
AB  - Tumor cells display features that are not found in healthy cells. How they become
      immortal and how their specific features can be exploited to combat tumorigenesis
      are key questions in tumor biology. Here we describe the long non-coding RNA
      cherub that is critically required for the development of brain tumors in
      Drosophila but is dispensable for normal development. In mitotic Drosophila
      neural stem cells, cherub localizes to the cell periphery and segregates into the
      differentiating daughter cell. During tumorigenesis, de-differentiation of cherub
      high cells leads to the formation of tumorigenic stem cells that accumulate
      abnormally high cherub levels. We show that cherub establishes a molecular link
      between the RNA-binding proteins Staufen and Syncrip. As Syncrip is part of the
      molecular machinery specifying temporal identity in neural stem cells, we propose
      that tumor cells proliferate indefinitely, because cherub accumulation no longer
      allows them to complete their temporal neurogenesis program.

PMID- 29580387
TI  - Synthesis of novel grafted hyaluronic acid with antitumor activity.
AB  - In our study, we aimed to synthesize novel grafted hyaluronic acid with cationic
      biodegradable polymer, poly (N-vinyl imidazole) (PVI), through free radical
      polymerization using potassium persulfate as initiator. The effect of various
      grafting factors including initiator and monomer concentrations, reaction time
      and temperature was studied on the percentage of grafting parameters such as;
      graft yield (% GY), grafting efficiency (% GE) and amount of homopolymer
      formation (% H). Maximum grafted HA was% GY = 235% and%GE = 83% obtained on
      optimum conditions at [In] = 17.5 mmol L-1, [M] = 1.25 mol L-1, Temp. = 50 
      degrees C, time = 1.5 h and [HA] = 0.025 mol L-1. The structure of grafted HA (HA
      g-PVI) was elucidated via various analysis tools such as; elemental analyses,
      FTIR, 1H NMR, XRD, TGA and Field emission scanning electron microscopy (FE-SEM).
      Hepatic and breast cancers are two common cancer types threatening people
      worldwide, so, the antitumor activity of two grafted HA samples (% GY = 155% and
      235%) was studied against hepatic cancer (HepG-2) and breast cancer cell lines
      (MCF-7) compared to unmodified HA and PVI. The results showed that antitumor
      activity of grafted samples was more than unmodified HA and increased with
      increasing the grafting percentage of PVI onto HA chains, also, the antitumor
      activity of tested samples against HepG-2 cell lines was higher than MCF-7 cell
      lines.

PMID- 29580388
TI  - Development of gelatin/carboxymethyl chitosan/nano-hydroxyapatite composite 3D
      macroporous scaffold for bone tissue engineering applications.
AB  - The present study delineates a relatively simpler approach for fabrication of a
      macroporous three-dimensional scaffold for bone tissue engineering. The novelty
      of the work is to obtain a scaffold with macroporosity (interconnected networks)
      through a combined approach of high stirring induced foaming of the
      gelatin/carboxymethyl chitosan (CMC)/nano-hydroxyapatite (nHAp) matrix followed
      by freeze drying. The fabricated macroporous (SGC) scaffold had a greater pore
      size, higher porosity, higher water retention capacity, slow and sustained
      enzymatic degradation rate along with higher compressive strength compared to
      that of non-macroporous (NGC, prepared by conventional freeze drying methodology)
      scaffold. The biological studies revealed the increased percentage of viability,
      proliferation, and differentiation as well as higher mineralization of
      differentiated human Wharton's jelly MSC microtissue (wjhMSC-MT) on SGC as
      compared to NGC scaffold. RT-PCR also showed enhanced expression level of
      collagen type I, osteocalcin and Runx2 when seeded on SGC. MUCT and histological
      analysis further revealed a penetration of cellular spheroid to a greater depth
      in SGC scaffold than NGC scaffold. Furthermore, the effect of cryopreservation on
      microtissue survival on the three-dimensional construct revealed significant
      higher viability upon revival in macroporous SGC scaffolds. These results
      together suggest that high stirring based macroporous scaffolds could have a
      potential application in bone tissue engineering.

PMID- 29580389
TI  - Electrochemical behavior of polypyrrole/chitosan composite coating on Ti metal
      for biomedical applications.
AB  - In the present work, the corrosion resistance performance and biocompatibility of
      polypyrrole/chitosan (PPy/CHI) composite coated Ti was studied. The deposition of
      composite coating was carried out by electropolymerization method. The deposited
      PPy/CHI composite coatings were different in morphology, structural, surface
      roughness and wettability compared PPy coated Ti. The presence of composite
      coating was confirmed by solid 13C NMR. The PPy/CHI composite coating showed
      enhanced microhardness and adhesion strength compared to the PPy coating. The
      corrosion protection ability of PPy/CHI composite coatings at various applied
      potentials was analyzed by dynamic electrochemical impedance spectroscopy (DEIS),
      exhibited higher impedance in all the potentials compared to uncoated and PPy
      coated Ti. The lower corrosion current density obtained for PPy/CHI-2 composite
      coating from polarization studies revealed increased corrosion protection ability
      in SBF solution. The stability of composite coating was confirmed by immersion
      studies. PPy/CHI-2 composite coating immersed in SBF solution enhances
      hydroxyapatite (HAp) formation.

PMID- 29580390
TI  - Carboxymethyl cellulose prepared from mesquite tree: New source for promising
      nanocomposite materials.
AB  - In the current article cellulose pulp extracted from mesquite tree was
      characterized and used as a raw material for preparation of carboxymethyl
      cellulose (CMC) which further used for preparing nanocomposite. CMC/Fe3O4
      nanocomposite was synthesized by co-precipitation of iron (II) and (III) salts by
      aqueous ammonia in CMC solution. Cellulose pulp, CMC and CMC/Fe3O4 materials were
      characterized by using FTIR, XRD, TGA, SEM and TEM analysis. The results showed
      that homogenous spherical magnetic nanoparticles with diameter ~25 nm were
      formed. The nanocomposite was further applied to remove methylene blue (MB) from
      aqueous solutions. The adsorption experiments showed the maximum adsorption
      capacity at pH 7. The adsorption results were analyzed by different isotherm and
      kinetic models and the results were fitted well with the Langmuir model and
      pseudo second-order model respectively. The current article showed that mesquite
      tree is a new resource for cellulose pulp which could be employed for preparing
      sustainable and environmentally friendly composite materials.

PMID- 29580391
TI  - Cellulose ultrafine fibers embedded with titania particles as a high performance
      and eco-friendly separator for lithium-ion batteries.
AB  - Mixtures of cellulose acetate (M.W. ~3 * 104 g/mol) dissolved in 75% v/v acetic
      acid in water (17% w/w) and ground anatase titania particles with diameters of
      197 +/- 75 nm (0%, 5% and 10% w/w) were electrospun at 17 kV with a fiber
      collection distance and a feed rate of 10 cm and 0.6 mL/h. Then, the fiber was
      treated with 0.5 M potassium hydroxide in ethanol. Rough regenerated cellulose
      (RC)-titania separators with diameters of ~310 nm and uniformly dispersed titania
      particles showed ~78% porosities. They decomposed at 300  degrees C, higher than
      the decomposition temperature of polyethylene separators (220  degrees C). Added
      titania particles increased the electrolyte wettability and lithium transference
      number (from 0.22 to 0.62). RC - 10% titania separator retained the capacity with
      79 mA h/g after 30 cycles and had excellent discharge capacity. These fascinating
      properties make RC-titania separator promising for lithium ion battery.

PMID- 29580392
TI  - Improved miscibility of PA6 and chitosan by the electric-field assisted phase
      inversion.
AB  - A facile and efficient method for the improved miscibility of natural
      polymer/synthetic polymer blends is reported here based on the electric-field
      driven phase inversion. We have employed bioderived chitosan (CS) and Polyamide-6
      (PA6) as an example since their blends are known to always result in a large
      scale phase separation (i.e. CS settles to the bottom of the blends as sediment)
      during phase inversion procedure. The condensed structure of the polymer blends
      has been well characterized, notably by the polarized attenuated total
      reflectance infrared spectroscopy and proton longitudinal relaxation time (T1)
      distribution. The application of an electric field can orient the polar groups
      which will hinder the crystallization of blends and also increase the interphase
      interaction between PA6 and CS. The miscibility of the PA6/CS blends has been
      characterized by scanning electron microscopy and confocal Raman spectroscopy. It
      is shown that this controllable hydrogen bonding environment, induced by the
      presence of electric field, indeed greatly hinder the sedimentation of CS without
      destroying its chemical structure. The improved miscibility of PA6/CS blends can
      thus significantly increase the toughness and generate a somewhat larger tensile
      strength.

PMID- 29580393
TI  - Synthesis of a bioadsorbent from jute cellulose, and application for aqueous Cd
      (II) removal.
AB  - A low-cost, high-adsorption-capacity, eco-friendly bioadsorbent for removing Cd2+
      from aqueous solution is reported. J-g-P(AM-co-AANa) was prepared by hydrolysis
      of the grafted copolymer, which was synthesized by free radical polymerization of
      acrylamide (AM) with jute fibers (JSE) pretreated by continuous screw-extrusion
      steam explosion. Fourier transform infrared and solid-state 13C nuclear magnetic
      resonance spectroscopies, confirmed that amino and carboxylate groups were
      introduced into J-g-P(AM-co-AANa). X-ray diffraction showed that the
      crystallinity of J-g-P(AM-co-AANa) was significantly lower than that of JSE. The
      surface morphology of bioadsorbent was investigated by scanning electron
      microscopy (SEM). The adsorption capacity of Cd2+ on J-g-P(AM-co-AANa) was
      evaluated for different solution pH values, contact times, and initial Cd2+
      concentrations. The adsorption kinetics followed the pseudo-second-order kinetic
      model, and the rate controlling step was chemisorption. The adsorption isotherm
      was well fitted by the Freundlich model, and the adsorption process was
      multilayer adsorption. The maximum adsorption capacity was 344.8 mg/g, which
      indicated that the bioadsorbent was effective for removing Cd2+ from aqueous
      solution.

PMID- 29580394
TI  - Size-dependent pharmacological activities of differently degraded fucoidan
      fractions from Fucus vesiculosus.
AB  - Fucose-containing sulfated glycans (syn. fucoidans) from brown algae exhibit a
      wide range of bioactivities and are therefore considered promising candidates for
      health-supporting and medical applications. In this study, we investigated the
      pharmacological activities of fucoidan from Fucus vesiculosus and 18 gradually
      depolymerized fractions, which were obtained by hydrothermal and H2O2 treatment,
      respectively. All the activities decreased with decreasing molecular mass (Mw)
      but to a different extent resulting in some modified pharmacological profiles in
      dependence on the Mw as well as on the degradation method. H2O2 treatment was not
      only more efficient, simpler and cheaper than hydrothermal degradation, but also
      led to superior activity profiles and additionally eliminated co-extracted
      contaminants. Compared to heparin, the prime example of biologically active
      sulfated glycans, evenly sized H2O2 fractions exhibited considerable effects
      being relevant for anti-inflammatory activity, however only negligible
      anticoagulant activity and FXII activating potency. Due to their improved
      biopharmaceutical characteristics and favorable activities, degraded fucoidan
      fractions are worth to be further investigated as anti-inflammatory and
      anticomplementary agents.

PMID- 29580395
TI  - Isolation and characterization of cellulose nanofibrils from Colombian Fique
      decortication by-products.
AB  - Fique fibers are extracted from Furcraea spp. leaves, with 5% average mass yield,
      using mechanical decortication. Juice, pulp and tow, the by-products of this
      process, amount 95% of the leaf weight and are considered waste. We extracted
      cellulose nanofibrils (CNF) from Fique tow, via ultrasound-assisted TEMPO
      followed by mechanical disintegration with sonication. Fique CNF exhibit
      diameters around 100 nm, degree of oxidation (DO) of 0.27 and surface charge
      density (sigma) of 1.6 mmol/g. Fique CNF aqueous suspensions show optical
      birefringence and high colloidal stability due to a high zeta potential (-53 mV).
      The morphology, chemical structure, crystallinity and phase transitions of Fique
      CNF were studied using FESEM, IR-ATR, XRD and TGA. We observed that the
      delignification pretreatment and the TEMPO reaction assisted by ultrasound
      significantly increase Fique CNF sigma and zeta potential, in contrast with the
      oxidation carried out without ultrasound or with raw (lignified) tow.

PMID- 29580396
TI  - Chitin nanocrystals prepared by oxidation of alpha-chitin using the
      O2/laccase/TEMPO system.
AB  - Laccase mediator oxidation was applied to chitin at pH 6.8 and 30  degrees C to
      prepare chitin nanocrystals with a catalytic amount of 2,2,6,6
      tetramethylpiperidine-1-oxyl radical (TEMPO). When 40 mM TEMPO and a total of 500
      U laccase were added to 1 g chitin, the yield of water-insoluble oxidized chitin
      was more than 95%, and the carboxylate content was 0.43 mmol/g. Adsorption of
      laccase molecules on chitin particles occurred in a buffer at pH 6.8, which may
      have been caused by electrostatic interactions between positively charged C2
      ammonium groups of chitin and anionically charged groups of laccase. Rod-like
      chitin nanocrystals (ChNCs) were obtained with average lengths and widths of 480
      +/- 200 nm and 24 +/- 17 nm, respectively, by sonication of the oxidized
      chitin/water suspensions. The O2/laccase/TEMPO oxidation caused no decrease in
      the degree of N-acetylation or the crystallinity of the original chitin based on
      FTIR and X-ray diffraction data.

PMID- 29580397
TI  - Double helix formation from non-natural amylose analog polysaccharides.
AB  - Double helix formation from the non-natural anionic and cationic amylose analog
      polysaccharides (amylouronic acid and amylosamine, respectively) was achieved
      through electrostatic interactions. A water-insoluble complex was obtained by
      simply mixing the two polysaccharides in water. The 1H NMR analysis indicated
      that the formation of the complexes with an approximately equimolar unit ratio
      from the two polysaccharides was resulted regardless of feed ratios for mixing.
      The powder X-ray diffraction (XRD) measurement suggested that the helix had
      larger sizes both in diameter and pitch compared with well-known amylose double
      helix. The formation of the double helical structure was also examined by
      theoretical calculations. The double helix models, differing in a chain polarity
      and a charge state of the residues, were constructed based on the 6-fold left
      handed amylose chain of the A-amylose crystal structure. Molecular dynamics
      calculations indicated that those with an antiparallel chain polarity retained an
      intertwined form. The antiparallel double helical model with the free form
      residues was suggested to be the most likely structure for the non-natural
      polysaccharides.

PMID- 29580398
TI  - Covalently bonded ionic liquid onto cellulose for fast adsorption and efficient
      separation of Cr(VI): Batch, column and mechanism investigation.
AB  - Combining the advantages of both cellulose and ionic liquid, ionic liquid
      functionalized cellulose (ILFC) as adsorbent was prepared through radiation
      grafting glycidyl methacrylate onto cellulose microsphere following by reaction
      with ionic liquid 1-aminopropyl-3-methyl imidazolium nitrate. Its adsorption
      properties towards Cr(VI) were investigated in batch and column experiments. In
      batch experiments, the adsorption kinetics was well fitted with pseudo-second
      order mode with equilibrium time of 2 h and the adsorption capacity reached 181.8
      mg/g at pH 2 calculated from Langmuir model. In fixed column, both Yoon-Nelson
      and Thomas models gave satisfactory fit to experimental data and breakthrough
      curves, and equilibrium adsorption capacity calculated by Thomas model was 161.0
      mg/g. Moreover, ILFC exhibited high selectivity towards Cr(VI) even in synthetic
      chrome-plating wastewater. Besides, adsorption/desorption test revealed ILFC can
      be regenerated and reused several times without obvious decrease in adsorbed
      amount. The adsorption process was demonstrated to anion exchange-reduction
      mechanism via XPS analysis.

PMID- 29580399
TI  - Durable antimicrobial cotton textiles coated sonochemically with ZnO
      nanoparticles embedded in an in-situ enzymatically generated bioadhesive.
AB  - An important preventive measure for providing a bacteria-free environment for the
      patients is the introduction of highly efficient and durable antibacterial
      textiles in hospitals. This work describes a single step sono-enzymatic process
      for coating of cotton medical textiles with antibacterial ZnO nanoparticles (NPs)
      and gallic acid (GA) to produce biocompatible fabrics with durable antibacterial
      properties. Cellulose substrates, however, need pre-activation to achieve
      sufficient stability of the NPs on their surface. Herein, this drawback is
      overcome by the simultaneous sonochemical deposition of ZnO NPs and the synthesis
      of a bio-based adhesive generated by the enzymatic cross-linking of GA in which
      the NPs were embedded. GA possesses the multiple functions of an antibacterial
      agent, a building block of the cross-linked phenolic network, and as a compound
      providing the safe contact of the coated materials with human skin. The ZnO NPs
      GA coated fabrics maintained above 60% antibacterial efficacy even after 60
      washing cycles at 75  degrees C hospital laundry regime.

PMID- 29580400
TI  - A promptly approach from monosaccharides of biomass to oligosaccharides via sharp
      quenching thermo conversion (SQTC).
AB  - In this study, a novel and facile approach of conversion monosaccharides (glucose
      and xylose) to oligosaccharides (Cello-oligosaccharides and Xylo
      oligosaccharides) was demonstrated. The approach did not introduce any chemical
      reagent and the preparation process could be environmentally friendly.
      Identification and quantification by ion chromatography (IC) and high performance
      liquid chromatography (HPLC) showed that the yields of COS and XOS reached to
      44.62% (38 s) and 47.09% (30 s) respectively at 500  degrees C reaction
      temperature coupled with sharp-quenching method. Structural characterization
      indicated that such oligosaccharides showed a degree of polymerization (DP) with
      2-6, and the units mainly linked by beta-(1 -> 4)-glycosidic bond.

PMID- 29580402
TI  - Preparation and characterization of green-nano-composite material based on
      polyaniline, multiwalled carbon nano tubes and carboxymethyl cellulose: For
      electrochemical sensor applications.
AB  - In this paper, we are presenting the preparation and characterization of
      "polyaniline/multiwalled carbon nanotubes/carboxymethyl cellulose" based novel
      composite material. It's morphological, thermal, structural, and electrochemical
      properties were investigated by using different instrumental techniques. During
      the in-situ chemical polymerization of aniline in the aqueous suspension of CMC
      and MWCNTs, the particle size change in two different ways "top to bottom" (low
      molecular weight oligomers grows in size) and "bottom to top" (long fibers of CMC
      fragmented in the reaction mixture). The combination of these two processes
      facilitated the fabrication of an integrated green-nano-composite material. In
      addition, a little amount of conductive nanofillers (MWCNTs) boosts the
      electrical and electrocatalytic properties of the material. Electron-rich centers
      of benzenoid rings exhibited pi-pi stacking with sp2 carbon of MWCNTs. CMC
      dominantly impact on the properties of PANI, negatively charged carboxylate group
      of CMC ionically bonded with protonated amine/imine. FTIR and Raman analysis
      confirmed that the material has dominated quinoid units and effective charge
      transfer. Hydroxyl and carboxyl groups and bonded water molecules of CMC results
      in a network of hydrogen bonds (which induced directional property).
      PANI/MWCNTs/CMC have nanobead-like structures (TEM analysis), large surface area,
      large pore volume, small pore diameter (BET and BJH studies) and good dispersion
      ability in the aqueous phase. Nanostructures of aligned PANI exhibited excellent
      electrochemical properties have attracted increasing attention. Modified carbon
      paste electrode was used for electrocatalytic detection of ascorbic acid (as a
      model analyte). The sensor exhibited a linear range 0.05 mM-5 mM, sensitivity
      100.63 MUA mM-1 cm-2, and limit of detection 0.01 mM. PANI/MWCNTs/CMC is suitable
      nanocomposite material for apply electroactive/conducting ink and membrane (which
      could be used in electrochemical sensor applications).

PMID- 29580401
TI  - Enhancement of transparent hydrogel sanxan production in Sphingomonas
      sanxanigenens NX02 via rational and random gene manipulation.
AB  - Polymer sanxan is a novel microbial polysaccharide produced by Sphingomonas
      sanxanigenens NX02, which can produce poly-3-hydroxybutyrate (PHB)
      simultaneously. A strategy of combining rational and random gene manipulation was
      investigated to improve the yield of sanxan. Several crucial PHB biosynthesis
      genes were deleted through homologous recombination, then the PHB-deficient
      mutant was treated with plasma mutagenesis to obtain NXdP, an engineering strain.
      Ultimately, the yield of purified sanxan produced by strain NXdP increased from
      14.88 +/- 0.83 g/L to 21.20 +/- 0.38 g/L in a 5 L bioreactor, while the cell dry
      weight (CDW) was decreased from 9.61 +/- 0.14 g/L to 3.12 +/- 0.15 g/L. The total
      precipitable material (crude sanxan) produced from NXdP showed higher zero-shear
      viscosity, light transmittance, and greater gel strength than that from NX02 due
      to the enhancement of its purity. The engineering strategies explored here are
      useful for engineering cell factories to produce other valuable metabolites.

PMID- 29580403
TI  - Tailor-made conductive inks from cellulose nanofibrils for 3D printing of neural
      guidelines.
AB  - Neural tissue engineering (TE), an innovative biomedical method of brain study,
      is very dependent on scaffolds that support cell development into a functional
      tissue. Recently, 3D patterned scaffolds for neural TE have shown significant
      positive effects on cells by a more realistic mimicking of actual neural tissue.
      In this work, we present a conductive nanocellulose-based ink for 3D printing of
      neural TE scaffolds. It is demonstrated that by using cellulose nanofibrils and
      carbon nanotubes as ink constituents, it is possible to print guidelines with a
      diameter below 1 mm and electrical conductivity of 3.8 * 10-1 S cm-1. The cell
      culture studies reveal that neural cells prefer to attach, proliferate, and
      differentiate on the 3D printed conductive guidelines. To our knowledge, this is
      the first research effort devoted to using cost-effective cellulosic 3D printed
      structures in neural TE, and we suppose that much more will arise in the near
      future.

PMID- 29580404
TI  - Improved antifungal activity and stability of chitosan nanofibers using cellulose
      nanocrystal on banknote papers.
AB  - Microorganisms can spread on the surface of banknotes and cause many infectious
      diseases. Chitosan nanofibers (CNFs) and cellulose nanocrystals (CNCs) are
      nanomaterials, which can affect the antimicrobial properties. In this study, the
      fungal species that grew on the surfaces of collected banknotes from different
      places were identified. To examine the antifungal effect of the both
      nanomaterials on the banknotes, the stable coatings using CNFs and CNCs emulsions
      were prepared by roller coating. The results revealed that the most colonies in
      the banknotes obtained from the bakeries and butcheries were Aspergillus sp.,
      whereas the colonies in bus terminals and the hospitals were Aspergillus niger
      and Penicillium, respectively. The results showed that the CNCs had no antifungal
      effect alone on the aforementioned species, but it could improve the antifungal
      effect, adhesion, and stability of CNFs on the banknote surfaces. This study
      suggested a new approach to decrease the infection spreads through banknotes.

PMID- 29580405
TI  - Physical characterization and modeling of chitosan/peg blends for injectable
      scaffolds.
AB  - Injectable scaffolds find many applications on the biomedical field due to
      several advantages on preformed scaffolds such as being able to fill any defect
      can be used in minimal invasion surgeries and are ready to use products. The most
      critical parameter for an injectable scaffold usage is its injectability, which
      can be related with rheological properties. Therefore, the objective of the
      present work was to increase knowledge about the critical parameters influencing
      injectability of biopolymers used for injectable scaffolds. Rheological and
      mechanical properties of a biopolymer blend in combination with injectability
      tests for a given design space controlled by the concentrations of both polymers
      and temperatures was made. Then those results were modeled to better understand
      the impact of parameters on injectability. The biopolymer blend chosen was
      Chitosan physically blended with Poly(ethylene glycol) where variations of both
      polymer concentrations and molecular weights were tested. Rheological and
      mechanical properties of all samples were determined, together with the injection
      force using a compression test at different injection conditions. All solutions
      were clear and transparent suggesting perfect miscibility. Rheological results
      were modeled using Ostwald-Waelle law and revealed a shear thinning pseudo
      plastic solution at any composition and temperature, being chitosan concentration
      the most influencing variable. Compression tests results revealed mean injection
      forces ranging from 9.9 +/- 0.06N to 29.9 +/- 0.65N and it was possible to
      accurately estimate those results. Simulations revealed draw speed as the most
      influencing parameter. Cell viability tests revealed a non-cytotoxic biopolymer
      blend.

PMID- 29580406
TI  - Novel method for holocellulose analysis of non-woody biomass wastes.
AB  - Compositional analysis of non-woody biomass is quite important to determine its
      possible applications. However, current standard methods developed for woody
      biomass compositional analysis have been revealed to be unsuitable when applied
      to non-woody biomass. Therefore, a novel and less-time consuming modified method
      which enables for a proper isolation of holocellulose in non-woody biomass
      samples while increasing lignin degradation has been developed. The novel method
      mainly consists in a treatment with sodium chlorite and glacial acetic acid at
      boiling point, which precludes changes in the holocellulose crystallinity degree
      or losses of carbohydrates, as shown by DSC, XRPD, and HPLC analysis. It was
      successfully applied to the determination of the structural components of 10
      different non-woody biomass samples. Also, its use revealed that non-woody
      biomass belongs to LHC and LCH groups in the biomass structural composition
      ternary diagram, which are completely different than the ones the woody biomass
      belongs to.

PMID- 29580407
TI  - Chitosan/waste coffee-grounds composite: An efficient and eco-friendly adsorbent
      for removal of pharmaceutical contaminants from water.
AB  - Waste coffee-grounds (WCG), a poorly explored source of biocompounds, were
      combined with chitosan (Cs) and poly(vinyl alcohol) (PVA) in order to obtain
      composites. Overall, WCG showed a good interaction with the polymeric matrix and
      good dispersibility up to 10 wt-%. At 5 wt-% WCG, the composite exhibited a
      noticeable enhancement (from 10 to 44%) of the adsorption of pharmaceuticals
      (metamizol (MET), acetylsalicylic acid (ASA), acetaminophen (ACE), and caffeine
      (CAF)) as compared to the pristine sample. The highest removal efficiency was
      registered at pH 6 and the removal followed the order ASA > CAF > ACE > MET. For
      all pharmaceuticals, the adsorption kinetics was found to follow the pseudo
      second order model, while the adsorption mechanism was explained by the
      Freundlich isotherm. Reuse experiments indicated that the WCG-containing
      composite has an attractive cost-effectiveness since it presented a remarkable
      reusability in at least five consecutive adsorption/desorption cycles.

PMID- 29580408
TI  - Factors affecting the properties of nitrocellulose emulsions: A comparative
      study.
AB  - In this study the influence of viscosity and chemical nature of dispersed phase,
      preparation conditions and storage temperature on the properties of
      nitrocellulose emulsions produced by gel emulsification (G) and direct mechanical
      emulsification (D) methods were examined. Chemical nature of dispersed phase had
      no effect on the drop size for both methods; however it had a significant effect
      on emulsion stability. Viscosity of dispersed phase did not considerably affect
      drop breakage process in route G, while strongly affected drop breakage in route
      D. Addition rate had no significant effect on the drop size produced by route D;
      while for route G high addition rate resulted in catastrophic phase inversion.
      The drop size produced by route D decreased dramatically by increasing stirring
      speed, whereas stirring speed had a minimal effect on the drop breakage process
      in route G. Finally, it was found that emulsion stability was greatly influenced
      by storage temperature.

PMID- 29580409
TI  - Conjugates of modified hyaluronic acid with amino compounds for biomedical
      applications.
AB  - Hyaluronic acid (HA) modified with an aldehyde group (HA-CHO) has enormous
      potential for the covalent attachment of the amino compounds and for the
      crosslinking of HA with bis or multi-functional amino linkers under physiological
      conditions. Modification of HA-CHO to its alpha,beta-unsaturated analogue
      (DeltaHA-CHO) generally increases the stability of the reversible imino
      attachment due to conjugation of the imine moiety with the adjacent CC double
      bound. Conjugation of a wide range of structurally different amines including the
      amines with enhanced biological activity were studied in detail. Results showed
      that the stabilities of the final conjugates DeltaHACHNR significantly depend on
      the chemical structure of the amine and on the pH value.

PMID- 29580410
TI  - Reinforcement of thermoplastic chitosan hydrogel using chitin whiskers optimized
      with response surface methodology.
AB  - To strengthen the mechanical strength of thermo-sensitive hydroxybutyl chitosan
      (HBC) hydrogel, chitin whiskers were used as sticker to fabricate reinforced HBC
      (HBCW) hydrogel by using response surface methodology. Unlike the intrinsic
      network of HBC hydrogel, HBCW hydrogel showed a laminar shape with firm
      structure. The preparation condition was optimized by three-factor-three-level
      Box-Behnken design. The maximum mechanical strength (1011.11 Pa) was achieved at
      50  degrees C, when the concentrations of HBC and chitin whiskers were 5.1 wt%
      and 2.0 wt%, respectively. The effects of temperature, pH value and NaCl
      concentration on mechanical strength of HBCW hydrogels were investigated via the
      oscillatory stress sweeps. The results showed that HBCW hydrogel could reach the
      maximum stiffness (~1126 Pa) at 37  degrees C pH 12.0. Low pH and high salty ions
      could decrease the stability of hydrogel, while chitin whiskers could increase
      the stress tolerance and related ruptured strain of HBCW hydrogels.

PMID- 29580411
TI  - Polysaccharides from Dendrobium huoshanense stems alleviates lung inflammation in
      cigarette smoke-induced mice.
AB  - The present work investigated the inhibitory activity of the polysaccharide from
      cultivated Dendrobium huoshanense (cDHP) on lung inflammation in cigarette smoke
      (CS)-induced mouse model. cDHP was mainly composed of mannose and glucose in a
      molar ratio of 1.89: 1.00, and had a backbone with linkages of 1,4-Manp, 1,4
      Glcp, 1,4,6-Manp and 1-Glcp. Hematoxylin and Eosin (HE) staining and
      immunohistochemistry analysis showed that cDHP can increase alveolar number,
      thicken alveolar wall, inhibit pulmonary bulla formation and decrease
      inflammatory cell infiltration as compared to the model group. ELISA
      determination revealed that cDHP can inhibit CS-induced enhancement in TNF-alpha
      and IL-1beta secretion in serum and lung. These results suggested that cDHP can
      resist CS-induced lung inflammation. Further, the phosphorylation analysis of
      p65, IkappaB, p38 and JNK as well as the DNA binding activity analysis of NF
      kappaB and AP-1 implied that the anti-inflammation function of cDHP is mediated
      via regulating NF-kappaB and MAPK signaling.

PMID- 29580412
TI  - Structural characterization of the exopolysaccharides from water kefir.
AB  - Water kefir is a beverage which is produced by initiating fermentation of a fruit
      extract/sucrose solution with insoluble kefir grains. Exopolysaccharides that are
      formed from sucrose play a major role in the kefir grain formation, but the
      exopolysaccharides in the kefir beverage and the detailed structural composition
      of the whole kefir grains have not been studied yet. Therefore, kefir grains and
      the corresponding kefir beverage were analyzed for exopolysaccharides by multiple
      chromatographic approaches and two-dimensional NMR spectroscopy. Furthermore,
      different fractionation techniques were applied to obtain further information
      about the exopolysaccharides. The exopolysaccharide-fraction of the investigated
      kefir beverage was predominantly composed of O3- and O2-branched dextrans as well
      as lower amounts of levans. The insoluble dextrans from the kefir grains were
      mostly O3-branched and contained an elevated portion of 1,3-linked glucose units
      compared to the soluble dextrans. The structurally different exopolysaccharides
      in water kefir suggest the involvement of multiple bacteria.

PMID- 29580413
TI  - Conductive nanostructured materials based on poly-(3,4-ethylenedioxythiophene)
      (PEDOT) and starch/kappa-carrageenan for biomedical applications.
AB  - Smart electroactive biomaterials are sought to allow the direct delivery of
      electrical, electrochemical and electromechanical signals to biological tissues.
      Specifically, poly-(3,4-ethylenedioxythiophene) (PEDOT) is a polymer of special
      interest attending to its biocompatibility, tuneable electrical conductivity and
      processing versatility. In this work, nanostructured PEDOT was synthesized using
      starch/kappa-carrageenan aerogels as templates. kappa-carrageenan biopolymer
      acted as doping agent of the conductive polymer to enhance the biocompatibility
      and the electrical response. The physicochemical, morphological, mechanical and
      electrical properties of the nanostructured PEDOT and templates were
      characterized. The incorporation of kappa-carrageenan to the nanostructured
      materials resulted in an increase in the compressive strength of ca. 40% and a
      decrease in the electrical impedance of one order-of-magnitude. The synergistic
      combination of the inherent electrical properties of the PEDOT, the advantageous
      features of kappa-carrageenan as doping agent and the porous morphology of the
      aerogel template resulted in electroactive PEDOT nanostructures with relevant
      properties for biomedical applications.

PMID- 29580414
TI  - Natural gum-type biopolymers as potential modified nonpolar drug release systems.
AB  - In this work, the relationship between surface properties and drug release
      mechanism from binary composition tablets formed by quetiapine fumarate and
      biopolymer materials was studied. The biopolymers correspond to xanthan and
      tragacanth gums, which are projected as modified drug release systems. The
      surface studies were carried out by the sessile drop method, while the surface
      free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical
      models. On the other hand, the drug release studies were performed by in vitro
      dissolution tests, where the data were analyzed through kinetic models of zero
      order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that
      depending on the type and the proportion of biopolymer, surface properties, and
      the drug release processes are significantly affected, wherein tragacanth gum
      present a usual erosion mechanism, while xanthan gum describes a swelling
      mechanism that controls the release of the drug.

PMID- 29580415
TI  - The novel application of chitosan: Effects of cross-linked chitosan on the fire
      performance of thermoplastic polyurethane.
AB  - In this paper, a novel flame retardant (ACS) was prepared by crosslinking
      chitosan with bis-(4-formylphenyl)-phenyl-phosphonate (ABPO). ACS in association
      with ammonium polyphosphate (APP) and organic modified montmorillonite (OMMT)
      were used to prepare flame retardant thermoplastic polyurethane (TPU) composite
      through melt blending. For the TPU sample containing 10% flame retardants, the
      limiting oxygen index was increased from 20.8 to 29.0%, the vertical burning (UL
      94) rating was upgraded from no rating to V-0, and the peak heat release rate was
      decreased from 1090 to 284 kW/m2. The thermal gravity analysis (TGA) indicated
      that ACS had excellent char formation ability and could greatly enhance the
      thermal stability of TPU. The tensile strength and elongation at break for flame
      retardant sample could reach 16.5 MPa and 1443% respectively.

PMID- 29580416
TI  - Fabrication of calcium phosphate-loaded carboxymethyl cellulose non-woven sheets
      for bone regeneration.
AB  - Calcium phosphate-loaded carboxymethyl cellulose non-woven sheets (CMC/CaP sheet)
      were fabricated and their potential to induce in vitro osteoblast differentiation
      and in vivo bone regeneration were investigated. The CMC/CaP sheets were prepared
      by alternately soaking protonated-CMC non-woven sheets in CaCl2 and Na2HPO4
      aqueous solutions. Because of its slow water uptake rate, the protonated-CMC was
      successfully loaded with a mixed phase of brushite and hydroxyapatite. In vitro,
      the CMC/CaP sheet induced osteoblast differentiation of human mesenchymal stromal
      cells (hMSCs), as shown by calcification and the upregulation of osteoblast
      marker genes. In absence of CaP, hMSCs on the CMC sheet had enhanced expression
      of alkaline phosphatase (ALP) only, indicative of early osteoblast
      differentiation. Finally, bone regeneration by the CMC/CaP sheet was demonstrated
      in a mouse calvarial defect model, based on micro-computed tomography (micro-CT),
      Masson's trichrome staining, and immunostaining for osteoblast markers. Cells
      expressing the transcription factor Sp7/Osterix, which is essential for
      osteoblast differentiation, were detected around the new bone. The combined
      effect of CMC and CaP enhanced osteoblast differentiation and the CMC/CaP non
      woven sheet was found to be an easy-to-handle and flexible scaffold for bone
      regeneration.

PMID- 29580417
TI  - Grafting polycaprolactone diol onto cellulose nanocrystals via click chemistry:
      Enhancing thermal stability and hydrophobic property.
AB  - Hydrophobic and thermally-stable cellulose nanocrystals (CNCs) were synthesized
      by polycarpolactone diol (PCL diol) grafting via click chemistry strategy. The
      synthesis was designed as a three-step procedure containing azide-modification of
      CNCs, alkyne-modification of PCL diol and sequent copper(I)-catalyzed azide
      alkyne cycloaddition reaction. The structure of azide-modified CNCs and alkyne
      modified PCL diol, the structure, hydrophobic ability and thermal stability of
      click products CNC-PCL were characterized. FTIR, XPS and H1 NMR results indicated
      a successful grafting of the N3 groups onto the CNCs, synthesis of PCL diol-CCH,
      and formation of the CNC-PCL material. CNC-PCL had enhanced dispersion in the non
      polar solvent chloroform owing to the well-maintained microscale size and PCL
      induced hydrophobic surface. The thermal stability of CNC-PCL was largely
      increased due to the grafting of thermally-stable PCL. This work demonstrates
      that click chemistry is an attractive modification strategy to graft CNCs with
      polyester chains for further potential application in polymer composites.

PMID- 29580418
TI  - Structure of water in hybrid cellulose acetate-silica ultrafiltration membranes
      and permeation properties.
AB  - Hybrid cellulose acetate (CA) silica (SiO2) (CA/SiO2) membranes were synthesized
      by promoting the in situ condensation between silanols from the SiO2 precursor
      and the COH or acetate groups from the CA polymer. For all the CA/SiO2 membranes,
      the ATR-FTIR peak assigned to (SiOC) proves the hybrid condensation reaction and
      confirms the synthesis of monophasic hybrid membranes. ATR-FTIR shows the
      presence of uncondensed highly reactive SiOH species, in membranes with silica
      contents higher than 20 mol%. Together with RMN studies, results show molecular
      water strongly hydrogen-bonded with SiOH groups, yielding a drastic decrease in
      the membrane hydraulic permeability, from 57 to 10 kg/h/m2/bar. The incorporation
      of 5 and 10 mol% of silica increased the hydraulic permeability from 32 to 82
      kg/h/m2/bar when compared to the CA membrane.

PMID- 29580419
TI  - Redox-sensitive nanoparticles based on 4-aminothiophenol-carboxymethyl inulin
      conjugate for budesonide delivery in inflammatory bowel diseases.
AB  - The purpose of this study was to develop an oral nanocarrier as budesonide
      delivery system and to evaluate its therapeutic potential for inflammatory bowel
      disease (IBD). The nanoparticles (NPs) based on an amphiphilic inulin polymer
      with 4-aminothiophenol (ATP) grafted onto carboxymethyl inulin (CMI) were
      prepared. The particle sizes were about 210.18 nm and had the obvious pH/redox
      sensitive swelling transitions. The drug-release study of NPs <-- >in vitro
      showed a low release rate (about 45 wt%) in GSH-free media, whereas high release
      rate (about 80 wt%) in the media containing 20 mM GSH, exhibiting a redox
      responsive property. Further in vivo experiments found the NPs tended to
      accumulate in inflamed sites, and exerted excellent therapeutic efficacy in
      comparison to drug suspension in colitis mice model. All the results demonstrated
      that the redox-sensitive NPs, based on amphiphilic inulin, may be used as colon
      targeted drug delivery for the treatment of IBD.

PMID- 29580420
TI  - Design of amphoteric chitosan flocculants for phosphate and turbidity removal in
      wastewater.
AB  - An amphoteric flocculant (CMC-CTA) was synthesized by grafting 3-chloro-2
      hydroxypropyl trimethylammonium chloride onto carboxymethyl chitosan (CMC). The
      turbidity and orthophosphate (Pi) removal properties of chitosan (CHI), CMC, and
      CMC-CTA were compared in the presence (and absence) of FeCl3 coagulant. At a
      fixed FeCl3 dosage, the effects of flocculant dosage, pH and settling time were
      evaluated. Turbidity removal (%) and optimal dosage (FeCl3; mg/L) was determined:
      CMC-CTA (95.8%;5), CHI (88.8%;7.0) and CMC (68.8%;9.0). The corresponding Pi
      removal (%) and dosage (mg/L) are listed: (93.4%;10), (90.6%;10), and (67.4%;5).
      Optimal turbidity and Pi removal occurred at pH 4, where CMC-CTA had greater
      efficiency over CMC and CHI. The turbidity removal kinetics was described by the
      pseudo-second-order model, while Pi removal followed the pseudo-first-order
      model. The removal process involves cooperative Coulombic interactions between
      the biopolymer/Fe(III)/Pi and/or kaolinite colloids, along with polymer bridging
      effects.

PMID- 29580421
TI  - Facile hydrothermal synthesis of Fe3O4@cellulose aerogel nanocomposite and its
      application in Fenton-like degradation of Rhodamine B.
AB  - A magnetic cellulose aerogel-supported Fe3O4 nanoparticles composite was designed
      as a highly efficient and eco-friendly catalyst for Fenton-like degradation of
      Rhodamine B (RhB). The composite (coded as Fe3O4@CA) was formed by embedding well
      dispersed Fe3O4 nanoparticles into the 3D structure of cellulose aerogels by
      virtue of a facile and cheap hydrothermal method. Comparative studies indicate
      that the RhB decolorization ratio is much higher in co-presence of Fe3O4 and H2O2
      than that in presence of Fe3O4 or H2O2 only, revealing that the Fe3O4@CA
      catalyzed Fenton-like reaction governed the RhB decolorization process. It was
      also found that almost 100% RhB removal was achieved in the Fenton-like system.
      Moreover, the composite exhibited higher catalytic activity than that of the
      individual Fe3O4 particles. In addition, the Fe3O4@CA catalyst retained ~97% of
      its ability to degrade RhB after the six successive degradation experiments,
      suggesting its excellent reusability. All these merits indicate that the green
      and low-cost catalyst with strong magnetic responsiveness possesses good
      potential for H2O2-driven Fenton-like treatment of organic dyestuff wastewater.

PMID- 29580422
TI  - Wound dressings from naturally-occurring polymers: A review on homopolysaccharide
      based composites.
AB  - Wound dressings are designed to support the wound bed and protect it from the
      factors that may delay or impede its healing such as contaminations and moisture
      loss, thereby facilitating and accelerating the healing process. The materials
      used to prepare wound dressings include natural and synthetic polymers, as well
      as their combinations, in the forms of films, sponges and hydrogels.
      Polysaccharides are naturally-occurring polymers that have been extensively used
      as wound dressing materials. Homopolysaccharides are a class of polysaccharides
      consist of only one type of monosaccharide. The current review intends to
      overview the studies in which wound dressings from naturally-occurring polymers,
      based on homopolysaccharides, were prepared and evaluated. Homopolysaccharides
      such as cellulose, chitosan, chitin, pullulan, starch and beta-glucan were
      considered.

PMID- 29580423
TI  - A novel enzymatic approach to nanocrystalline cellulose preparation.
AB  - In this work, conditions for an enzymatic pretreatment prior to NCC isolation
      from cotton linter were assessed. Different cellulase doses and reaction times
      were studied within an experimental design and NCC were obtained. At optimal
      enzymatic conditions (20U, 2 h), a total yield greater than 80% was achieved and
      the necessary enzymatic treatment time was reduced 90%. Different intensities of
      enzymatic treatments led to proportional decreases in fiber length and viscosity
      and also were inversely proportional to the amount of released oligosaccharides.
      These differences within fibers lead to quantitative differences in NCC: increase
      in acid hydrolysis yield, reduction of NCC surface charge and crystallinity
      increase. Benefits produced by enzymatic treatments did not have influence over
      other NCC characteristics such as their sulfur content (~1%), size (~200 nm),
      zeta potential (~-50 mV) or degree of polymerization (~200). Evidence presented
      in this work would reduce the use of harsh sulfuric acid generating a cleaner
      stream of profitable oligosaccharides.

PMID- 29580424
TI  - Corrigendum to "Synthesis and melt processing of cellulose esters for preparation
      of thermoforming materials and extended drug release tablets" [Carbohydr. Polym.
      177 (2017) 105-115].

PMID- 29580425
TI  - A comparative study of gelatin and starch-based nano-composite films modified by
      nano-cellulose and chitosan for food packaging applications.
AB  - Environmental concerns have led to extensive research for replacing polymer-based
      food packaging with bio-nano-composites. In this study, incorporation of nano
      cellulose into gelatin and starch matrices is investigated for this purpose.
      Chitosan is used to improve mechanical, anti-fungal and waterproof properties.
      Experiments are designed and analyzed using response surface methodology. Nano
      Cellulose is synthesized via acid hydrolysis and incorporated in base matrices
      through wet processing. Also, tensile strength test, food preservation,
      transparency in visible and UV and water contact angle are performed on the nano
      composite films. DSC/TGA and air permeability tests are also performed on the
      optimal films. The results show that increasing nano-cellulose composition to 10%
      leads to increase the tensile strength at break to 8121 MN/m2 and decrease the
      elongation at break. Also, increasing chitosan composition from 5% to 30% can
      enhance food preservation up to 15 days.

PMID- 29580426
TI  - A new biodegradable sisal fiber-starch packing composite with nest structure.
AB  - A new completely biodegradable sisal fiber-starch packing composite was proposed.
      The effects of fiber content and alkaline treatment on the cushioning property of
      the composites were studied from energy absorption efficiency, cellular
      microstructure and compatibility between fiber and starch. With increasing fiber
      content, the nest structure of composites becomes dense first and then loosens,
      resulting in initial enhancement and subsequent weakening of the cushioning
      property of the composites. The composite with 4:13 mass ratio of fiber and
      thermoplastic starch (TPS) exhibit the optimal cushioning property. Alkaline
      treatment increases the compatibility between sisal fiber and TPS, promotes the
      formation of dense nest structure, thereby enhances the cushioning property of
      the composites. After biodegradability tests for 28 days, the weight loss of the
      composites was 62.36%. It's found that the composites are a promising replacement
      for expandable polystyrene (EPS) as packing material, especially under large
      compression load (0.7-6 MPa).

PMID- 29580427
TI  - Synthesis of chitosan-based micelles for pH responsive drug release and
      antibacterial application.
AB  - The over- and inefficient release of antibiotics from common delivery systems
      causes the development of drug-resistant bacteria. In the present work, methoxy
      poly(ethylene glycol)-poly(epsilon-caprolactone)-chitosan/montmorillonite
      (MPC/MMT) hybrid multilayer films were constructed for bacterial infections and
      pH-dependent release of the hydrophobic drug triclosan (TCA). The thickness of
      the (MPC-T/MMT)10 multilayer films was 384.4 +/- 26.5 nm, and the TCA loading
      dosage was 2.4 MUg/cm2. Staphylococcus aureus, Escherichia coli and
      Staphylococcus epidermidis were used in the antibacterial tests. pH responsive
      TCA release from the prepared multilayer films was examined by measuring the
      bactericidal activity of the films after immersion in PBS (pH 7.4) or MES (pH
      5.5) and zone of inhibition on nutrient agar. In vitro bacterial shake-flask,
      zone of inhibition and live/dead staining results demonstrated the high
      sterilization efficiency of the films. Furthermore, cell biocompatibility
      measurements toward L929 fibroblasts and human lens epithelial cells showed no
      adverse effects of the multilayer film.

PMID- 29580428
TI  - Effects of sodium salt types on the intermolecular interaction of sodium
      alginate/antarctic krill protein composite fibers.
AB  - Sodium alginate (SA) and antarctic krill protein (AKP) were blended to fabricate
      the SA/AKP composite fibers by the conventional wet spinning method using 5%
      CaCl2 as coagulation solution. The sodium salt was added to the SA/AKP solution
      to adjust the ionization degree and intermolecular interaction of composite
      system. The main purpose of this study is to investigate the influences of sodium
      salt types (NaCl, CH3COONa, Na2SO4) on the intermolecular interaction of SA/AKP
      composite fibers. The intermolecular interaction, morphology, crystallinity,
      thermal stability and mechanical properties of SA/AKP composite fibers were
      analyzed by fourier transform infrared spectroscopy (FT-IR), scanning electron
      microscope (SEM), x-ray diffraction (XRD), thermogravimetric analysis (TGA). The
      results show that the types of sodium salt have obvious influences on the content
      of both beta-sheet, intermolecular hydrogen bond, breaking strength and surface
      morphology in SA/AKP composite fibers, but have a negligible effect on the
      crystallinity and thermal stability.

PMID- 29580429
TI  - Facile synthesis of cellulose nanofiber nanocomposite as a SERS substrate for
      detection of thiram in juice.
AB  - There has been growing interest in the use of nanocellulose-based substrate for
      surface-enhanced Raman spectroscopy (SERS) applications. This study aimed to use
      cellulose nanofibers (CNF) to develop novel CNF-based nanocomposite as a SERS
      substrate. CNF were cationized with ammonium ions and then interacted with
      citrate-stabilized gold nanoparticles (AuNPs) via electrostatic attraction to
      form uniform nanocomposites. The CNF-based nanostructures were loaded with AuNPs
      that were firmly adhered on the CNF surfaces, providing a three-dimensional
      plasmonic SERS platform. A Raman-active probe molecule, 4-aminothiophenol, was
      selected to evaluate the sensitivity and reproducibility of CNF-based SERS
      substrate. The intensity of SERS spectra obtained from CNF/AuNP nanocomposite was
      20 times higher than that from the filter paper/AuNP substrate. The SERS
      intensity map demonstrates good uniformity of the CNF/AuNP substrate. CNF/AuNP
      nanocomposites were used in rapid detection of thiram in apple juice by SERS and
      a limit of detection of 52 ppb of thiram was achieved. These results demonstrate
      that CNF/AuNP nanocomposite can be used for rapid and sensitive detection of
      pesticides in food products.

PMID- 29580430
TI  - Hydroxyethyl methacrylate grafted carboxy methyl tamarind (CMT-g-HEMA)
      polysaccharide based matrix as a suitable scaffold for skin tissue engineering.
AB  - Patho-physiologies related to skin are diverse in nature such as burns, skin
      ulcers, atopic dermatitis, psoriasis etc. which impose severe bio-medical
      problems and thus enforce requirement of new and healthy skin prepared through
      tissues engineering methodologies. However, fully functional and biodegradable
      matrix for attachment, growth, proliferation and differentiation of the relevant
      cells is not available. In the present study, we introduce a set of hydrogels
      synthesized by incorporation of a synthetic monomer (Hydroxyethlmethacryate) with
      a semi-synthetic polymer backbone (carboxy methyl tamarind, CMT) in different
      mole ratios. We termed these materials as CMT:HEMA based hydrogels and these were
      characterized by different physico-chemical techniques, namely by X-Ray
      Diffraction, SEM and Dynamic Light Scattering. Biocompatibility studies with
      HaCaT, NIH-3T3 and mouse dermal fibroblasts confirm that this material is
      biocompatible. MTT assay further confirmed that this material does not have any
      cytotoxic effects. Assays for mitochondrial functionality such as ATP assay and
      mitochondrial reactive oxygen (ROS) generation also suggest that this material is
      safe and does not have any cytotoxicity. Hemolytic assay with red blood cells and
      acute skin irritation test on SD Rats confirmed that this material is suitable
      for ex-vivo application in future. We suggest that this hydrogel is suitable for
      in-vivo applications and may have clinical and commercial importance against skin
      disorders.

PMID- 29580431
TI  - Effect of cellulose nanocrystals on the crystallization behavior and enzymatic
      degradation of poly(butylene adipate).
AB  - Cellulose nanocrystals (CNCs) are nature-resourced nanoparticles and have been
      widely used to improve performance of biodegradable polyesters. Two types of CNCs
      respectively prepared by sulphuric acid hydrolysis (aCNCs) and ammonium
      persulfate oxidation (oCNCs) processes were incorporated into poly(butylene
      adipate) (PBA) matrix to regulate its crystallization behavior and enzymatic
      degradation performance. Thermal and X-ray diffraction analysis revealed that
      both aCNCs and oCNCs could promote the crystallization ability and lamellar
      thickening of alpha-form PBA, while oCNCs showed stronger promotion than aCNCs.
      Optical morphology study indicated that both two types of CNCs enhanced the
      nucleation ability of PBA. Furthermore, the mechanism of crystallization
      promotion of CNCs on PBA was further discussed and attributed to the "memory
      effect" in the melt state of PBA/CNCs composites, which was originated from the
      hydrogen-bonding interaction between CNCs and PBA chains. The enzymatic
      degradation testing proved that CNCs could slower down degradation rate of PBA
      and PBA/oCNCs composites possessed lower degradation rate than PBA/aCNCs
      composites.

PMID- 29580433
TI  - Post-treatment surveillance imaging in lymphoma.
AB  - Appropriate post-treatment management of patients with lymphoma has been
      controversial, with imaging frequently performed as post-treatment surveillance.
      The goal of post-treatment imaging is to identify relapse prior to clinical
      symptoms, when the burden of disease is lower and the possibility of effective
      salvage therapy and cure are greater. However, little data exist to support the
      performance of surveillance imaging after completion of treatment, with the vast
      majority of studies suggesting there is no clinical benefit to surveillance
      imaging in asymptomatic patients. Ongoing efforts seek to identify a subset of
      patients with a higher risk of relapse that might benefit from surveillance
      imaging, though financial and other costs associated with imaging are non
      negligible and must be considered. Here we summarize the current data regarding
      post-treatment surveillance imaging in lymphoma.

PMID- 29580432
TI  - Surveillance imaging following definitive radiotherapy for non-small cell lung
      cancer: What is the clinical impact?
AB  - Lung cancer is the leading cause of cancer death worldwide. Recurrence rates at
      all stages are high, but evidence-based post-treatment surveillance imaging
      strategies to detect recurrence are poorly defined, and salvage options are
      frequently limited. A number of national and international oncology guidelines
      address post-treatment imaging, but are largely based on low-level, retrospective
      evidence because of a paucity of high-quality data, particularly in regard to
      cost-effectiveness and quality-of-life endpoints. Given the lack of randomized
      data addressing appropriate surveillance imaging modality and interval following
      definitive treatment of lung cancer, there remains an unmet clinical need.
      Meaningful surveillance endpoints should include the financial impact, patient
      quality-of-life outcomes, and access-to-care issues associated with intensive
      follow-up to ensure that guidelines reflect quality and sustainability. A need
      for prospective randomized data on the subject of imaging surveillance after
      definitive local therapy remains an unmet need, and an opportunity for
      collaboration and further research.

PMID- 29580434
TI  - Surveillance imaging following treatment of head and neck cancer.
AB  - Post-treatment surveillance is an important component in the treatment of head
      and neck cancers, especially as the proportion of human papilloma virus-positive
      cancers increases. Early detection of recurrences or second malignancies can
      increase success and minimize the toxicity of salvage treatment. Unfortunately,
      there are no consensus guidelines on the frequency and modality of post-treatment
      imaging. Computed tomography, ultrasound, magnetic resonance imaging and positron
      emission tomography-computed tomography (PET-CT) all have unique advantages and
      disadvantages when used as surveillance imaging. There is evidence that PET-CT
      may be the most sensitive of these modalities, but further research is needed to
      show an improvement in patient outcomes. Institutions will benefit most from a
      surveillance plan that is consistent and tailored to the individualized needs of
      their patients. This review focuses on the available evidence for different
      imaging modalities and general guidelines for developing an institution-specific
      practice pattern.

PMID- 29580435
TI  - Cell-free DNA as a post-treatment surveillance strategy: current status.
AB  - Circulating tumor DNA (ctDNA) consists of cell-free DNA (cfDNA) fragments that
      are released from tumor cells into the bloodstream. ctDNA harbors cancer-specific
      genetic and epigenetic alterations that allow its detection and quantification
      using a variety of emerging techniques. The promise of convenient non-invasive
      access to the complex and dynamic molecular features of cancer through peripheral
      blood has galvanized translational researchers around this topic with compelling
      routes to clinical implementation, particularly in the post-treatment
      surveillance setting. Although analysis methods must contend with the small
      quantities of ctDNA present in most patients, and the relative over-abundance of
      background cfDNA derived from normal tissues, recent technical innovations have
      led to dramatic improvements in the sensitivity of ctDNA detection. As a result,
      ever more studies are investigating the clinical utility of ctDNA for
      applications in (1) treatment response assessment, (2) identification of emerging
      resistance mechanisms, (3) minimal residual disease detection, and (4)
      characterization of clonal heterogeneity and selection. In this review, we
      describe the detection methods currently used in clinical studies to assess low
      fractions of ctDNA, as well as their utility in the applications previously
      described. Finally, we address current limitations that have hampered the
      clinical implementation of ctDNA analysis for post-treatment surveillance and
      propose steps that could be made to address them.

PMID- 29580436
TI  - The Surgical Management of Prostate Cancer.
AB  - Prostate cancer is a heterogeneous disease with a variable natural history.
      Therefore, optimal management remains challenging. While many men with newly
      diagnosed prostate cancer may be candidates for active surveillance, there are
      others who will benefit from aggressive local therapy. Radical prostatectomy is
      associated with improvements in cancer-specific mortality, metastasis-free
      survival, and need for palliative treatments when compared with observation in
      several randomized controlled trials. Additionally, radical prostatectomy may
      have some oncologic benefit over radiation therapy. All aggressive therapy for
      prostate cancer negatively impacts erectile function and urinary continence. The
      decision for which treatment modality to pursue should incorporate shared
      decision making and consider cancer risk and severity in addition to patient
      preferences.

PMID- 29580437
TI  - Second-line therapy in patients with metastatic castration-resistant prostate
      cancer with progression after or under docetaxel: A systematic review of nine
      randomized controlled trials.
AB  - Treatment decisions are challenging in patients with metastatic castration
      resistant prostate cancer with progression after or under docetaxel. The current
      review systematically searched the published literature on all treatment options,
      and assessed the risk of bias and quality of evidence. It found the best
      available evidence for effective prolongation of overall survival and progression
      free survival for abiraterone acetate plus prednisone versus placebo plus
      prednisone and enzalutamide versus placebo. Other treatment modalities could be
      beneficial for individual patients by taking into consideration the: selection
      criteria of the randomized clinical trials, risk of bias, subgroup analyses, and
      quality of life and adverse events. Further research is needed to determine the
      sequence, timing asnd combination of different treatments.

PMID- 29580438
TI  - "Mind the Gap" Revisited.

PMID- 29580439
TI  - Response to letter to the editor on 'Mind the gap'.

PMID- 29580441
TI  - Visiting Black Patients: Racial Disparities in Security Standby Requests.

PMID- 29580440
TI  - Corrigendum to "Central insulin dysregulation and energy dyshomeostasis in two
      mouse models of Alzheimer's disease" [Neurobiol. Aging 58 (2017) 1-13].

PMID- 29580442
TI  - Integrated Patient Centered Approach to Treating Opioid Use Disorder.

PMID- 29580443
TI  - The Relationship Between Structural Racism and Black-White Disparities in Fatal
      Police Shootings at the State Level.
AB  - OBJECTIVE: The objective of this study was to discern the relationship between
      state-level structural racism and Black-White disparities in police shootings of
      victims not known to be armed. METHODS: Using a Poisson regression, we evaluated
      the effect of structural racism on differences between states in Black-White
      disparities in fatal police shootings involving victims not known to be armed
      during the period from January 1, 2013 through June 30, 2017. We created a state
      racism index, which was comprised of five dimensions: (1) residential
      segregation; and gaps in (2) incarceration rates; (3) educational attainment; (4)
      economic indicators; and (5) employment status. RESULTS: After controlling for
      numerous state-level factors and for the underlying rate of fatal shootings of
      black victims in each state, the state racism index was a significant predictor
      of the Black-White disparity in police shooting rates of victims not known to be
      armed (incidence rate ratio: 1.24; 95% confidence interval, 1.02-1.50). For every
      10-point increase in the state racism index, the Black-White disparity ratio of
      police shooting rates of people not known to be armed increased by 24%.
      CONCLUSION: These findings suggest that structural racism is an important
      predictor of the Black-White disparity in rates of police shootings of unarmed
      victims across states.

PMID- 29580444
TI  - Medical Simulation as a Vital Adjunct to Identifying Clinical Life-Threatening
      Gaps in Austere Environments.
AB  - BACKGROUND: Maternal mortality and morbidity are major causes of death in low
      resource countries, especially those in Sub-Saharan Africa. Healthcare workforce
      scarcities present in these locations result in poor perioperative care access
      and quality. These scarcities also limit the capacity for progressive development
      and enhancement of workforce training, and skills through continuing medical
      education. Newly available low-cost, in-situ simulation systems make it possible
      for a small cadre of trainers to use simulation to identify areas needing
      improvement and to rehearse best practice approaches, relevant to the context of
      target environments. METHODS: Nurse anesthetists were recruited throughout Sierra
      Leone to participate in simulation-based obstetric anesthesia scenarios at the
      country's national referral maternity hospital. All subjects participated in a
      detailed computer assisted training program to familiarize themselves with the
      Universal Anesthesia Machine (UAM). An expert panel rated the morbidity/mortality
      risk of pre-identified critical incidents within the scenario via the Delphi
      process. Participant responses to critical incidents were observed during these
      scenarios. Participants had an obstetric anesthesia pretest and post-test as well
      as debrief sessions focused on reviewing the significance of critical incident
      responses observed during the scenario. RESULTS: 21 nurse anesthetists, (20% of
      anesthesia providers nationally) participated. Median age was 41 years and median
      experience practicing anesthesia was 3.5 years. Most participants (57.1%) were
      female, two-thirds (66.7%) performed obstetrics anesthesia daily but 57.1% had no
      experience using the UAM. During the simulation, participants were observed and
      assessed on critical incident responses for case preparation with a median score
      of 7 out of 13 points, anesthesia management with a median score of 10 out of 20
      points and rapid sequence intubation with a median score of 3 out of 10 points.
      CONCLUSION: This study identified substantial risks to patient care and provides
      evidence to support the feasibility and value of in-situ simulation-based
      performance assessment for identifying critical gaps in safe anesthesia care in
      the low-resource settings. Further investigations may validate the impact and
      sustainability of simulation based training on skills transfer and retention
      among anesthesia providers low resource environments.

PMID- 29580445
TI  - Health Literacy (HL) & Health-Related Quality of Life (HRQL) Among Minority Men.
AB  - Health literacy remains a key factor in the continuance of health disparities in
      our society as health related quality of life can be negatively affected by
      limited health literacy. This study explores how limited health literacy among
      minority men, attending a community health fair, correlates with their health
      related quality of life. Findings reflect that minority men who possess lower
      levels of health literacy experience lower self-reported quality of life.
      Directions for healthcare providers, community health educators and future
      research approaches are provided.

PMID- 29580446
TI  - A Little Effort Can Withstand the Hardship: Fielding an Internet-Based
      Intervention to Prevent Depression among Urban Racial/Ethnic Minority Adolescents
      in a Primary Care Setting.
AB  - BACKGROUND: This study explored the implementation of Chicago Urban Resiliency
      Building (CURB), a randomized clinical trial designed as an Internet-based
      primary care depression prevention intervention for urban African American and
      Latino adolescents. METHODS: We utilized a mixed methods analysis to explore four
      aims. First, we estimated the percent of at-risk adolescents that were
      successfully screened. Second, we examined clinic site factors and performance.
      Third, primary care providers (n = 10) and clinic staff (n = 18) were surveyed to
      assess their knowledge and attitudes about the intervention. Fourth, clinic staff
      (nursing and medical assistant) interviews were analyzed using thematic analysis
      to gather perspectives of the implementation process. RESULTS: We found that the
      estimated percent of at-risk adolescents who were successfully screened in each
      clinic varied widely between clinics with a mean of 14.48%. Daily clinic
      communication was suggestive of greater successful screening. Feasibility of
      screening was high for both primary care providers and clinic staff. Clinic staff
      exit interviews indicated the presence of community barriers that inhibited
      successful implementation of the intervention. CONCLUSION: This study shares the
      challenges and successes for depression screening and implementing Internet-based
      mental health interventions for urban racial/ethnic minority adolescents in
      primary care settings.

PMID- 29580447
TI  - Is Unsedated Colonoscopy Gaining Ground Over Sedated Colonoscopy?
AB  - Colorectal cancer (CRC) is a prevalent cancer with high global incidence and a
      leading cause of cancer death worldwide. CRC screening is important for early
      cancer detection and prevention. Most premalignant adenomas can be identified and
      removed before they become malignant. Colonoscopy plays a vital role in reducing
      the risk for developing CRC. Although screening programs with colonoscopy have
      been implemented in many countries and considered beneficial for a number of
      people, this technique is generally associated with anxiety, embarrassment, pain,
      and discomfort, resulting in lack of adherence to the recommended screening
      guidelines. In the US, colonoscopy is mostly performed under sedation, thereby
      causing amnesia and analgesia. In contrast to sedated colonoscopy, which has been
      associated with some disadvantages, unsedated colonoscopy exhibits advantages and
      has been preferred over sedated colonoscopy in numerous cancer centers worldwide.
      This review enumerates the features of sedated and unsedated colonoscopy with the
      use of the current relevant evidence-based literature. Unsedated colonoscopy can
      be a reasonable option for routine and unscheduled CRC screening.

PMID- 29580448
TI  - Hospital Admissions, Mortality and Comorbidities Among New York State Sickle Cell
      Patients, 2005-2013.
AB  - Analyses of administrative and large data sources in Sickle Cell Disease (SCD)
      can answer questions not suitable for prospective study but have been hampered by
      lack of validated methods to adjust for individual comorbidities and lack of
      baseline utilization data over time. We sought to develop a database to
      characterize inpatient SCD care across New York State and generate a re-weighted
      sickle-cell specific Charlson Comorbidity index (S-CCI) for use in future large
      data SCD research. We identified 18,541 individual SCD patients admitted to New
      York State hospitals between 2005 and 2013 from the SPARCS database. We present
      data from both a randomly selected derivation cohort, used to develop the S-CCI
      and a validation cohort, The S-CCI resulted in small improvements in model fit
      and discrimination while using fewer covariates, allowing a more parsimonious
      model. Despite being the most common comorbidity, chronic pulmonary disease was
      not predictive of mortality. Mortality per hospitalization was 0.61%. Many
      patients (32%) were admitted only once during the nine year period. However, the
      majority was admitted more frequently with over 15% of patients being admitted
      more than once per year.

PMID- 29580449
TI  - Medical Students Rate Black Female Peers as Less Socially Connected.
AB  - BACKGROUND: Social and cultural outcomes are critically important in medical
      education. A large medical school located in the United States implemented a
      learning community model intended to promote social and cultural growth among its
      medical students. The purpose of this study was to evaluate the degree to which
      medical students from the same peer cohort were socially connected across racial
      and sex groups. METHODS: Because most assessments involving social and cultural
      outcomes involve self-reported data of a personal nature, the possibility of
      social desirability bias is increased. To mitigate this threat, this study
      utilized a novel method for measuring medical students social connectedness by
      having peers in one's advisory college provide social connectedness ratings about
      one another. RESULTS: While surface level results did not reveal any significant
      differences, a closer inspection of data revealed Black females were less
      socially connected with medical student peers from their cohort than other peer
      groups. DISCUSSION: Possible explanations for this are discussed. Future research
      should continue to investigate the experiences of Black females in medical
      schools so as to better understand the needs of this important and valuable
      subpopulation of students.

PMID- 29580450
TI  - Opioid Utilization by Pregnant Women with Sickle Cell Disease and the Risk of
      Neonatal Abstinence Syndrome.
AB  - BACKGROUND: Pregnant women with sickle cell disease (SCD) are at increased risk
      of maternal and fetal complications. There are limited data on the outcome of the
      treatment of VOCs with opioids in relation to neonatal complications during
      pregnancy. METHODS: This is a retrospective cohort study of women with SCD from
      January 1999 to December 2008. Women with SCD were identified by ICD-9 codes and
      matched 2:1 to a control group of women on methadone for opioid dependence. The
      primary outcome was the rate of neonatal abstinence syndrome (NAS). Secondary
      outcomes included the mean NAS score prior to treatment and the length of
      treatment. Statistical analysis was performed using SPSS. RESULTS: Twenty-one
      women with SCD who delivered a total of 23 neonates were included. The rate of
      NAS among infants born to women with SCD who were treated with opioids at any
      time was 22% compared to 54% in the methadone controls (p = .010). The rate of
      NAS was 27% among infants born to women taking opioids daily compared to 54% in
      the methadone control group (p = .062). CONCLUSIONS: Neonates born to women with
      SCD who are treated with daily opioids are at a similar risk for developing NAS
      as those born to mothers on methadone for opioid dependence. Neonates born to
      women with SCD treated with episodic opioids are at a significantly lower risk
      for developing NAS than those born to women on methadone for opioid dependence.

PMID- 29580451
TI  - Racial Differences in Heart Age and Impact on Mortality.
AB  - BACKGROUND: Heart age is an estimate of the age of a person's cardiovascular
      system given their cardiovascular disease (CVD) risk factors. The difference
      between a person's chronological age and heart age (excess heart age) represents
      their added CVD risk. OBJECTIVE: To examine racial differences in excess heart
      age and whether race impacts the association between excess heart age and CVD
      mortality. METHODS: This analysis included 5110 participants (2449 non-Hispanic
      white, 1287 non-Hispanic black, and 1374 Mexican-American) from the NHANES III
      who were free of CVD. Heart age was calculated using the sex-specific non
      laboratory-based Framingham risk prediction functions. Multivariable Cox
      proportional-hazards regression models were used to evaluate the relationship
      (overall and by race) between excess heart age and CVD mortality. RESULTS: Mean
      excess heart age was greatest in non-Hispanic blacks (13.0 years), followed by
      Mexican-Americans (10.5 years), and non-Hispanic whites (8.5 years); p < 0.001
      for pairwise differences. Over a mean follow-up of 13.0 years, 394 CVD deaths
      occurred. Each 10 years of excess heart age was associated with 65% increased
      risk of CVD mortality (HR, 95% CI: 1.65, 1.53-1.78). This association was
      stronger in non-Hispanic whites (1.83, 1.63-2.02) compared to non-Hispanic blacks
      (1.50, 1.29-1.72) and Mexican American (1.60, 1.33-1.87), interaction p = 0.065.
      CONCLUSIONS: Compared to non-Hispanic whites, non-Hispanic blacks and Mexican
      Americans have more excess heart age, but the risk of CVD death for the same
      level of excess heart age appears more pronounced in non-Hispanic whites. Further
      investigation is needed to show the usefulness of these findings in directing
      future efforts and resource allocation for reduction of health disparities
      between ethnic groups.

PMID- 29580452
TI  - Effect of Age, Gender, and Sun Exposure on Ethnic Skin Photoaging: Evidence
      Gathered Using a New Photonumeric Scale.
AB  - BACKGROUND: African-Americans are less affected by photoaging than lighter skin
      individuals. Although scales for photoaging have been developed for Caucasians
      and Asians, no scale exists for African-Americans. AIM: To develop a photonumeric
      scale for photoaging and to determine factors that contribute to photoaging in
      African-Americans. METHODS: Five participants' photographs were selected as
      standards to create a 9-point photonumeric scale (0 = none, 8 = most severe).
      Three blinded dermatologists used the scale to grade the remaining participants'
      photographs. RESULTS: Interrater reliabilities were 0.775 (95% CI: 0.635, 0.880)
      for trial 1 and 0.832 (0.747, 0.883) for trial 2. Intrarater reliabilities,
      assessed over a 1 week interval, were 0.863 (0.727, 0.940), 0.928 (0.890, 0.954),
      and 0.866 (0.739, 0.935) for the three graders, indicating strong agreement.
      Photoaging scores were then correlated with participants' survey on lifestyle
      factors, which yielded age as a significant predictor (r = 0.91, p < 0.001).
      Furthermore, multiple regression model to predict facial photoaging (adjusted R2
      = 0.849) selected age (b1 = 0.111, p < 0.001), sun exposure (b2 = 0.206, p =
      0.014), and gender (b2 = -0.388, p = 0.063) as the most important variables.
      CONCLUSIONS: A reliable photonumeric scale for photoaging in African Americans
      was developed. Age, sun exposure, and male gender were found to be contributory
      factors to photoaging.

PMID- 29580453
TI  - "We Would Still Find Things to Talk About": Assessment of Mentor Perspectives in
      a Systemic Lupus Erythematosus Intervention to Improve Disease Self-Management,
      Empowering SLE Patients.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder
      with significant disparate impact on African American women. The current study
      sought to highlight how the Peer Approaches to Lupus Self-management (PALS)
      intervention worked bi-directionally wherein both women with SLE leading the
      disease self-management program (mentors), and those participants who served as
      mentees, were empowered toward greater disease self-efficacy. METHODS: Data was
      captured for this study in two formats from the seven mentors participating in
      the pilot study: 1) mentor logs and 2) mentor interviews with the principle
      investigator. This information was then analyzed for themes relating to their
      experience within the study. RESULTS: We found that empowerment was facilitated
      by mentors taking their mentorship responsibilities seriously and seeking several
      avenues for collaboratively developing success with their mentees. Mentors
      reported that although challenges arose, their desire for success resulted in
      multiple approaches to be flexible and responsive to the needs of their mentees.
      Additionally, reciprocity was found to be a vital element of the program.
      CONCLUSIONS: Key thematic areas supported our ability to demonstrate the
      usefulness of a peer mentoring program for SLE disease self-management on evoking
      empowerment through reciprocal relationships among mentors and mentees within our
      study population. Furthermore the feedback from PALS participants yielded very
      rich and contextual information that can be used as a thematic guide for
      developing and refining evidence-based interventions that seek to incorporate
      empowerment into disease self-management efforts for women suffering from SLE.

PMID- 29580455
TI  - Development of Rope Connected Life-Saving Equipment for Transferring Numerous
      People.
AB  - BACKGROUND: This study is focused on a rapid and safe transfer when there are
      many people who need rescuing in unapproachable location. Generally, a stretcher,
      a basket or a mesh drawing is used to transfer injured people or survivors in the
      emergency rescue, however, it turned out that it takes long time to transfer a
      number of people with a stretcher and it is difficult to transfer injured people
      safely with a basket or a mesh drawing. It would expect to transfer many people
      who need rescuing promptly and harmlessly. METHODS: In this article, Targeted
      Acceptable Responses to Generated Events of Tasks (TARGETS), an event-based team
      performance measurement methodology was used to investigate the effects of
      Mission Oriented Protective Posture (MOPP) on the behavioral processes underlying
      team performance during simulated rescue tasks while wearing chemical protective
      equipment. In addition, this study determined which team processes were related
      to team performance outcomes. Results of six primary analyses indicated that team
      process performance was not degraded by MOPP 4 on any rescue task and that the
      team processes critical for successful task performance are task-dependent.
      RESULTS: As a result, authors have developed a new life-saving equipment.
      Numerous people who need rescuing can be quickly and safely rescued and
      transferred to the hospital with it. From a medical point of view, it reduces the
      risk of secondary damage from transport and helps avoid missing the golden time
      for first aid caused by delay in transferring emergency patients as numerous
      people can be transferred safely and quickly. CONCLUSION: The article is due to
      introduce the equipment which can transfer people who need rescuing promptly and
      effectively in a situation such as when numerous people need rescuing in the
      mountain. In a rescue situation such as mountain rescue, rope connected life
      saving equipment is dropped to the rescue site with a rope from a rescue
      helicopter and laying down the injured on the life-saving equipment body and
      equip life-saving equipment to the rope consecutively. In this way, it is
      expected to transfer the injured rapidly and safely.

PMID- 29580454
TI  - Characterizing Mobility Limitations Among Older African American Men.
AB  - This study represents an effort to contribute to the limited body of research on
      biopsychosocial contextual factors that influence or contribute to mobility
      limitations for older African American men. Specifically, we were interested in
      examining associations between socio-demographic, physical and emotional health
      experiences with mobility limitations. A secondary analysis of 1666 older African
      American men was performed to investigate socio-demographic, mental and physical
      health correlates to a specific measures of mobility limitation. In the final
      model, difficulty with self-care, severe pain interference, and problems with
      usual activities were most strongly associated with mobility limitations. Men who
      were married were significantly less likely to experience mobility limitations.
      Findings highlighted the relationship between mobility limitations and difficulty
      performing activities of daily living. Additional research should examine the
      impact of poor emotional health and the buffering effects of marriage on mobility
      for older African American men, a population at high risk of experiencing
      disparate health outcomes.

PMID- 29580456
TI  - Pseudo-Exfoliation of the Lens Capsule: Relation to "True" Exfoliation of the
      Lens Capsule as Reported in the Literature and Role in the Production of Glaucoma
      Capsulocuticulare.

PMID- 29580457
TI  - Letter by Derkenne et al. regarding the article, "The use of trained volunteers
      in the response to out-of-hospital cardiac arrest - the GoodSAM experience".

PMID- 29580458
TI  - Reply to: Letter by Derkenne et al. regarding the article, 'The use of trained
      volunteers in the response to out-of-hospital cardiac arrest - The GoodSAM
      experience.'

PMID- 29580459
TI  - Electrocardiographic patterns in postresuscitation patients?

PMID- 29580460
TI  - Reply to: Electrocardiographic patterns in postresuscitation patients?

PMID- 29580461
TI  - Effects of Respiratory Training on Heart Rate Variability and Baroreflex
      Sensitivity in Individuals with Chronic Spinal Cord Injury.

PMID- 29580462
TI  - Response to Letter to the Editor regarding "Effects of respiratory training on
      heart rate variability and baroreflex sensitivity in individuals with chronic
      spinal cord injury".

PMID- 29580463
TI  - Correction.

PMID- 29580464
TI  - Correction.

PMID- 29580465
TI  - Quorum sensing system-regulated genes affect the spoilage potential of Shewanella
      baltica.
AB  - Large yellow croaker (Pseudosciaena crocea) is a popular and nutritious but also
      highly perishable fish species, with Shewanella baltica being the primary
      spoilage bacteria during low-temperature storage. Clarifying the factors
      promoting spoilage will facilitate efforts to predict and control the shelf life
      of foods. This study focused on spoilage-related genes in two Shewanella baltica
      strains with different spoilage potentials. Using whole genome sequencing and
      alignment, three distinguishing genes (torT, cysM and trxB) were identified.
      Further protein sequence comparison and protein structure modeling revealed
      possible motifs responsible for the spoilage activity. Moreover, diketopiperazine
      (DKP) quorum sensing (QS) signaling molecules regulated biofilm formation and
      spoilage gene expression, indicating a relationship between the QS system,
      biofilm formation and spoilage potential. Our results suggest that DKPs and
      spoilage genes are potential targets for developing novel food antiseptics, as
      well as new markers for fish product spoilage.

PMID- 29580466
TI  - Integrated combined effects of temperature, pH and sodium chloride concentration
      on biofilm formation by Salmonella enterica ser. Enteritidis and Typhimurium
      under low nutrient food-related conditions.
AB  - Salmonella enterica is a major foodborne bacterial pathogen. This forms biofilms
      on surfaces and persists, depending on the strain and the environment. The
      integrative interaction of temperature (T; 13-39  degrees C), pH (5-8) and sodium
      chloride (NaCl) concentration (0.5-8.5%) on biofilm formation by two S. enterica
      strains (ser. Enteritidis and Typhimurium) was here evaluated under low nutrient
      conditions. This was achieved using response surface methodology to model the
      combined effect of each factor on the response, through mathematical quadratic
      fitting of the outcomes of a sequence of designed experiments. These last were
      executed by incubating stainless steel coupons carrying sessile bacteria, for 24
      h, in 1:10 diluted tryptone soya broth, under 15 different combinations of three
      independent factors (T, pH and NaCl). For each strain, a second order polynomial
      model, describing the relationship between biofilm formation (log CFU/cm2) and
      the factors (T, pH and NaCl), was developed using least square regression
      analysis. Both derived models predicted the combined influences of these factors
      on biofilm formation, with agreement between predictions and experimental
      observations (R2 >= 0.96, P <= 0.0001). For both strains, the increase of NaCl
      content restricted their sessile growth, while under low salinity conditions
      (NaCl < 4%) biofilm formation was favored as pH increased, regardless of T.
      Interestingly, under low salt content, and depending on the strain, biofilm
      formation was either favored or hindered by increasing T. Thus, 34.5 and 13 
      degrees C were the T predicted to maximize biofilm formation by strains
      Enteritidis and Typhimurium, respectively, something which was also
      experimentally verified. To sum, these models can predict the interactive
      influences of crucial food-related factors on biofilm growth of a significant
      foodborne pathogen towards the efforts to limit its persistence in food industry.

PMID- 29580467
TI  - Extracts of black garlic exhibits gastrointestinal motility effect.
AB  - In this studied, extracts of black garlic on the improvement of gastrointestinal
      function, antioxidant activity, total polyphenols, total flavonoids and total
      polysaccharides were evaluated. Results showed that the black garlic n-butanol
      fraction extract (BA) had significantly increased effect within small intestine
      in vitro, while the ethyl acetate fractions had no significant effect on small
      intestine in vitro. Increase of 5-HT4 content effectively stimulated the
      gastrointestinal peristalsis, which enhanced its gastrointestinal tract emptying,
      and promoted defecation. As for antioxidant activity test, the water extract was
      more effective in SOD activity test, DPPH radical scavenging rates, ferric
      reducing antioxidant power and reducing power. In addition, the water fraction
      was simulated by gastric acid digestion and hydrolysis, and the small intestine
      was isolated after acid hydrolysis (AW). It was found that the water fraction
      extract after acid hydrolysis did significantly improve the intestinal
      contraction rate. In short, extract of black garlic could effectively promote
      gastrointestinal motility and promote defecation. The active compounds were
      highly polar ingredients since water extract of black garlic exhibits most
      significant effect on improving gastrointestinal function.

PMID- 29580468
TI  - Processed cheese as a polymer matrix composite: A particle toolkit for the
      replacement of milk fat with canola oil in processed cheese.
AB  - In this study, we show that the replacement of milk fat with canola oil in a
      model caseinate-based imitation cheese product to increase its nutritional value
      can be done by treating processed cheese as a particle filled gel network. Using
      microscopy, model imitation cheese products with different lipid phases were
      found to have similar microstructures where fat or oil appears as inert particle
      fillers in a continuous protein network. Using a texture profile analyzer, we
      show that the textural properties of model imitation cheese are dependent on the
      material properties of the inert filler. Addition of rigid particle fillers
      generally results in greater reinforcement of the matrix (i.e., increased
      hardness). The addition of oat fiber particles at 5% volume fraction to model
      cheese containing 51% milk fat and 49% canola oil resulted in a product with
      similar functionalities (i.e., hardness, oil stability, and meltability) as that
      of model cheese containing 100% milk fat. The current study therefore shows that
      the addition of edible non-fat particles for matrix reinforcement can be used as
      an alternative method for reducing saturated fats in foods while keeping other
      desirable properties of the product.

PMID- 29580469
TI  - Comparison of fresh watermelon juice aroma characteristics of five varieties
      based on gas chromatography-olfactometry-mass spectrometry.
AB  - Qualitative and quantitative analysis and odor active value (OAV) calculation
      were applied to identify the aroma-active compounds of fresh watermelon juice in
      five varieties: Seedless, Jingxin, Lianfa, Qilin, and Texiaofeng. Principal
      component analysis and cluster analysis were selected to compare the similarity
      and difference among watermelons juices. Fifty-five volatiles were identified in
      watermelon juice in five varieties, among which 6 volatiles were identified for
      the first time in watermelon. (Z)-6-nonenal, (E, Z)-2,6-nonadienal, (E)-2
      nonenal, and (E, E)-2,4-nonadienal contributed greater to aroma profiles than
      alcohols due to lower threshold through odor active values. It was indicated by
      principal component analysis and cluster analysis that watermelon juices were
      separated into three groups, Jingxin, Lianfa-Texiaofeng, and Seedless-Qilin,
      whose characteristic volatiles were aldehydes, alcohols, and ketones
      respectively. The average distance between JX and the other varieties was higher
      than that of others through cluster analysis, indicating that the aroma of
      Jingxin differed from that of the other four varieties greatly.

PMID- 29580470
TI  - Degradation of carotenoids in dehydrated pumpkins as affected by different
      storage conditions.
AB  - The degradation kinetics of carotenoids in dehydrated pumpkins, stored at 4, 25,
      and 40  degrees C under air or controlled atmosphere conditions (N2), was
      evaluated using reversed-phase high performance liquid chromatography coupled
      with diode array and mass spectrometry detectors. The degradations of predominant
      carotenoids including beta-carotene, alpha-carotene and lutein depended on the
      storage temperature, the storage duration as well as the presence of oxygen,
      which was following the first-order kinetics. The temperature dependence of
      reaction constants were well explained by the Arrhenius relationship. The
      activation energy (Ea) for carotenoids degradation ranged from 23.69 kJ/mol for
      lutein in N2-packaged dehydrated pumpkins to 13.82 kJ/mol for beta-carotene in
      air-packaged samples. Lutein was less degradable than alpha-carotene and beta
      carotene in dehydrated pumpkins during storage. Higher all-E-carotenoid
      degradation in N2-packaged dehydrated pumpkins stored at 40  degrees C occurred
      than that stored at lower temperature under N2 or air storage, and those storage
      conditions were beneficial to the formation of Z-isomers (e.g., 15-Z-beta
      carotene and 13-Z-beta-carotene). Storage under N2 at 4  degrees C enhanced the
      retention of all-E-carotenoids in dehydrated pumpkins. Thus, package atmosphere
      should be paid more attention during long-term storage.

PMID- 29580471
TI  - The xylooligosaccharide addition and sodium reduction in requeijao cremoso
      processed cheese.
AB  - The addition of xylooligosaccharide (XOS), sodium reduction and flavor enhancers
      (arginine and yeast extract) on the manufacture of requeijao cremoso processed
      cheese was investigated. The addition of XOS resulted in a denser and compact
      structure, with increased apparent viscosity, elasticity (G') and firmness (G*).
      The addition of XOS and yeast extract improved the rheological and
      physicochemical properties (decrease in viscosity and particle size and increase
      in melting rate) and sensory characteristics (improvement in salty and acid
      taste, greater homogeneity, and lower bitter taste). In addition, a positive
      effect of arginine was observed in the sensory characteristics of the requeijao
      cremoso processed cheese, but without improvements in the physicochemical and
      rheological characteristics. Overall, the XOS addition and sodium reduction
      proportionated the development of a healthier processed cheese formulation.

PMID- 29580472
TI  - Effect of outer water phase composition on oil droplet size and yield of
      (w1/o/w2) double emulsions.
AB  - In this study the effect of various emulsifiers (whey protein isolate (WPI), Na
      caseinate, and Tween 20) and thickeners (xanthan and pectin) present in the outer
      water phase, w2, on oil droplet size and yield of the inner water phase, w1, of
      (w1/o/w2) double emulsions was investigated. Double emulsions stabilized by Tween
      20 had smaller oil droplet sizes and higher yields in comparison to emulsions
      stabilized by WPI and Na-caseinate. Gelation of the inner water droplets w1
      increased yield by 20% for all emulsifiers. Upon the addition of thickeners, the
      increasing viscosity of the outer water phase, w2, facilitated oil droplet
      breakup. This resulted in smaller oil droplets and lower yields. When pectin was
      used as a thickener, in comparison to xanthan, an additional decrease in yield
      was observed. The yield decreased to values close to zero indicating that all
      inner water droplets w1 were lost during emulsification. We conclude that type of
      hydrophilic emulsifier, properties of inner water droplets, viscosity ratio of
      continuous and dispersed phase, as well as type of thickener influence oil
      droplet size and yield of w1 phase of double emulsions. This work provides a
      better understanding of how composition influences the properties of double
      emulsions and how this can be used to design double emulsions as fat replacers in
      more complex food systems.

PMID- 29580473
TI  - Genotypic characterization of ESBL-producing E. coli from imported meat in South
      Korea.
AB  - Twenty extended-spectrum beta-lactamase (ESBL)-producing E. coli strains were
      isolated from imported meat in South Korea. ESBL strains of E. coli were detected
      in chicken (14/20) more often than in pork (6/20) and beef (0/20); the highest
      number (12/20) was detected in Brazilian meats. The blaCTX-M genes were
      predominant in meats from many countries. E. coli from pork imported from France
      produced the blaCTX-M-58 enzyme, which has never been documented previously in
      ESBL-producing bacteria from clinical or environmental sources. Additionally, the
      coexistence of the blaCTX-M-2 and blaOXA-1 enzymes in EC12-5 isolate was found
      for the first time in an ESBL E. coli isolate. A rare blaCTX-M type, blaCTX-M-25,
      was found in 40% of ESBL E. coli isolates. Phenotypic susceptibility testing
      showed that E. coli isolates were resistant to up to eleven antibiotics,
      including ciprofloxacin. For the first time, a new combination in an integron
      gene cassette, aacA4-cmlA6-qacEDelta1, was found in an E. coli isolate from
      poultry imported from Brazil. Three E. coli ST117 isolates, from an avian
      pathogenic lineage producing CTX-M-94, harbored fimH, fyuA, iutA, papC, rfc, and
      traT virulence genes and were not susceptible to quinolones. For the first time,
      rfc and papG virulence factors were detected in ESBL E. coli strains isolated
      from meat products. Even though E. coli CC21 and CC22 were obtained from meats
      from the USA and Brazil, respectively, they had a similarity coefficient higher
      than 99% in rep-PCR and the same MLST type (ST117), phenotypic antibiotic
      resistance pattern, integron gene (qacEDelta1), and plasmid DNA profile. This
      study indicates that imported meat products may be a source of ESBL-producing E.
      coli strains in South Korea.

PMID- 29580474
TI  - Transport of cowpea bean derived peptides and their modulator effects on mRNA
      expression of cholesterol-related genes in Caco-2 and HepG2 cells.
AB  - This work studied the cell transport of peptidase-generated peptides from cowpea
      bean proteins and their effects on mRNA expression of cholesterol-related genes
      in intestinal and liver cells. The <=3 kDa hydrolysate was obtained and incubated
      with Caco-2 intestinal cells using Transwell(r) plates. HepG2 liver cells were
      incubated with synthetic analogues of peptides (MELNAVSVVHS and MELNAVSVVSH)
      identified by "de novo" peptide sequencing in the Caco-2 monolayer permeates. The
      mRNA expression of NPC1L1, ABCA1 and ABCG1 was measured in Caco-2 cells, in the
      presence or absence of <=3 kDa hydrolysate and the expression of HMGCR, SREBP2,
      LXRalpha, AMPK1, was determined in the HepG2 cells in the presence or absence of
      synthetic peptides. Exposure of Caco-2 cells to cowpea <=3 kDa hydrolysate (2.5
      and 5 mg/mL) increased ABCG1 expression at 6 h and 12 h. SREBP2, HMGCR and LDLR
      mRNA levels were reduced in HepG2 cells after 24 h of treatment with MELNAVSVVHS
      peptide (50 MUM and 100 MUM). These results suggest that MELNAVSVVHS peptide is
      able to cross intestinal barrier and to modulate genes involved in cholesterol
      homeostasis.

PMID- 29580475
TI  - Viscozyme L pretreatment on palm kernels improved the aroma of palm kernel oil
      after kernel roasting.
AB  - With an interest to enhance the aroma of palm kernel oil (PKO), Viscozyme L, an
      enzyme complex containing a wide range of carbohydrases, was applied to alter the
      carbohydrates in palm kernels (PK) to modulate the formation of volatiles upon
      kernel roasting. After Viscozyme treatment, the content of simple sugars and free
      amino acids in PK increased by 4.4-fold and 4.5-fold, respectively. After kernel
      roasting and oil extraction, significantly more 2,5-dimethylfuran, 2
      [(methylthio)methyl]-furan, 1-(2-furanyl)-ethanone, 1-(2-furyl)-2-propanone, 5
      methyl-2-furancarboxaldehyde and 2-acetyl-5-methylfuran but less 2-furanmethanol
      and 2-furanmethanol acetate were found in treated PKO; the correlation between
      their formation and simple sugar profile was estimated by using partial least
      square regression (PLS1). Obvious differences in pyrroles and Strecker aldehydes
      were also found between the control and treated PKOs. Principal component
      analysis (PCA) clearly discriminated the treated PKOs from that of control PKOs
      on the basis of all volatile compounds. Such changes in volatiles translated into
      distinct sensory attributes, whereby treated PKO was more caramelic and burnt
      after aqueous extraction and more nutty, roasty, caramelic and smoky after
      solvent extraction.

PMID- 29580477
TI  - Thermal treatment of skim milk concentrates in a novel shear-heating device:
      Reduction of thermophilic spores and physical properties.
AB  - Endospores of thermophilic bacilli are a major concern for producers of dairy
      powders. In this study, we heat treated 10 different spore suspensions at 110 
      degrees C in skim milk and skim milk concentrate (36% dry matter) of the species
      Geobacillus stearothermophilus (10 min) and Anoxybacillus flavithermus (5 min) in
      a new shear-heating device. The highest log reduction in skim milk concentrate
      was 3.5. The death behavior of the spores was strain dependent. Particle
      formation and Maillard reaction were observed. By increasing the shear-rate up to
      1500 s-1 the particle size was reduced for both heating times (D90 reduction:
      57.4 and 77.0%, respectively). The particle size was lessened by a reduction of
      dry matter of 27%, compared to 36%. This work emphasizes, that heat treatment of
      concentrated dairy products represents a technological option to reduce
      thermophilic spores in skim milk concentrate and powders produced thereof.

PMID- 29580476
TI  - Correlating the properties of different carioca bean cultivars (Phaseolus
      vulgaris) with their hydration kinetics.
AB  - This work explained how the intrinsic properties of beans affects the hydration
      process. For that, different properties of six cultivars of carioca bean (a
      variety of common bean) were analyzed to verify the correlation with their
      hydration kinetics characteristics (hydration rate, lag phase time and
      equilibrium moisture content), using a Multiple Factorial Analysis (MFA): the
      chemical composition (starch, protein, lipids, minerals (Mg, P, S, K, Ca, Mn, Fe,
      Cu, Zn), functional groups from the seed coat analyzed by FT-IR), physical
      properties (size, 1000 grain weight, seed coat thickness, energy to penetrate the
      bean) and microstructure. Only few properties correlated with the hydration
      kinetics characteristics of the studied bean, comprising both composition and
      structure. The fat content, potassium content, specific surface, and the protein
      to lipids ratio correlated with the lag phase time, which is related with the
      seed coat impermeability to water. The necessary energy to perforate the seed
      coat correlated negatively with the hydration rate. It was concluded that the
      hydration of beans process is a complex phenomenon and that despite being from
      the same variety of legume, any change due to agronomic enhancement may affect
      their hydration process kinetics.

PMID- 29580478
TI  - Supersaturation of calcium citrate as a mechanism behind enhanced availability of
      calcium phosphates by presence of citrate.
AB  - Dissolution of amorphous calcium phosphate (ACP) in aqueous citrate at varying pH
      has been studied with perspective of increasing availability of calcium from
      sidestreams of whey protein, lactose and/or cheese production or on development
      of new functional foods. ACP formed as an initial precipitate in 0.10 mol L-1
      equimolar aqueous calcium chloride, sodium citrate, and sodium hydrogenphosphate
      was used as model for mineral residues formed during milk processing. Upon
      acidification of the ACP suspension by hydrochloric acid decreasing pH from 6.5
      to 4.5, the transformations of ACP occurred through an 8 h period of
      supersaturation prior to a slow precipitation of calcium citrate tetrahydrate.
      This robust supersaturation, which may explain increased availability of calcium
      phosphates in presence of citrate, presented a degree of supersaturation of 7.1
      and was characterized by precipitation rates for 0.10 mol L-1 equimolar aqueous
      calcium chloride, sodium hydrogencitrate, and sodium hydrogenphosphate with pH
      5.5, and for 0.10 mol L-1 equimolar aqueous calcium chloride, sodium
      hydrogencitrate, and sodium dihydrogenphosphate with pH 4.1, with a degree of
      supersaturation of 2.7. The crystallization processes were similar according to
      Avrami's model with a half-life for precipitation of approximately 5 h
      independent of the degree of supersaturation. Ion speciation based on measurement
      of pH, and total concentrations of calcium, phosphate and citrate, and of
      conductivity and calcium ion activity during precipitation indicates a low
      driving force for precipitation with calcium citrate complex dominating at pH 5.5
      and calcium hydrogencitrate complex dominating at pH 4.1. Calcium hydrogencitrate
      is suggested to be the species involved in the crystal growth followed by solid
      state transformation to calcium citrate tetrahydrate.

PMID- 29580479
TI  - Health benefits of ancient grains. Comparison among bread made with ancient,
      heritage and modern grain flours in human cultured cells.
AB  - Nowadays the higher nutritional value of whole grains compared to refined grains
      is recognized. In the last decade, there has been a renewed interest in the
      ancient wheat varieties for producing high-value food products with enhanced
      health benefits. This study compared two ancient grains, two heritage grains, and
      four modern grains grown in the same agronomic conditions considering not only
      their chemical characteristics, but also their biological effects. Whole grain
      flours were obtained and used to make bread. Bread was in vitro digested, the
      digesta were supplemented to HepG2 cells, and the biological effects of
      supplementation were evaluated. In addition, cells previously supplemented with
      the different digested bread types were then exposed to inflammatory agents to
      evidence possible protective effects of the pre-treatments. Despite the
      impossibility to discriminate bread made with different grains based on their
      chemical composition, results herein reported evidence that their supplementation
      to cultured cells exerts different effects, confirming the potential health
      benefits of ancient grains. This research represents an advancement for the
      evaluation of the apparent positive effects of ancient grains and the formulation
      of cereal-based products with added nutritional value.

PMID- 29580480
TI  - Chemical characterization complemented with chemometrics for the botanical origin
      identification of unifloral and multifloral honeys from India.
AB  - Chemical fingerprints based on FTIR spectra, phenolics and volatiles were studied
      for a total of 30 honey types of eight different botanical origin i.e. litchi,
      neem, ginger, eucalyptus, lemon (unifloral) and Kashmiri white, BR Hills & Pan
      India honey (Multifloral). Chemometrics based on principal component analysis
      (PCA) was used as a complementary tool for chemical fingerprint of honey. ATR
      FTIR had a good predictive capability to discriminate among honey when conjugated
      with chemometric tools, providing the rapid first-line of classification for
      honey. The specific phenolic compounds identified were homovanillic acid for
      neem, zingerone and gingerol for ginger, tricetin for eucalyptus, hesperitin and
      naringenin for lemon honey. Analysis of volatiles led to identification of odor
      active compounds such as azadirachtin for neem and zingiberene in ginger honey
      for the first time, whereas cis-rose oxide for litchi, 2-hydroxycineole for
      eucalyptus and methyl anthranilate & limonene diol for lemon honey as per
      previous studies which were well correlated with PCA of phenolics and volatiles.

PMID- 29580481
TI  - Impact of wall material physicochemical characteristics on the stability of
      encapsulated phytochemicals: A review.
AB  - Phytochemicals are plant-derived chemicals that have a number of protective or
      health-promoting properties. However, their health benefits and thus commercial
      potential can be restricted due to their instability to environmental factors
      such as moisture, heat, light, oxygen etc. A common approach to improve stability
      is via encapsulation whereby the phytochemical is encased inside a wall material,
      thereby forming a protective barrier between the phytochemical and the external
      environment. The impact of a wide range of wall materials and their combinations
      on the stability of various phytochemicals has been studied in the last twenty
      years. This review focuses on the specific inherent physicochemical
      characteristics of the wall material as well as the encapsulation process
      dependant physical characteristics that has shown to have the greatest impact on
      the stability of encapsulated phytochemicals. The information contained in this
      review could assist researchers in addressing some of the most important
      considerations when designing a wall material for increased phytochemical
      stability.

PMID- 29580482
TI  - Growth of non-toxigenic Clostridium botulinum mutant LNT01 in cooked beef: One
      step kinetic analysis and comparison with C. sporogenes and C. perfringens.
AB  - The objective of this study was to investigate the growth kinetics of Clostridium
      botulinum LNT01, a non-toxigenic mutant of C. botulinum 62A, in cooked ground
      beef. The spores of C. botulinum LNT01 were inoculated to ground beef and
      incubated anaerobically under different temperature conditions to observe growth
      and develop growth curves. A one-step kinetic analysis method was used to analyze
      the growth curves simultaneously to minimize the global residual error. The data
      analysis was performed using the USDA IPMP-Global Fit, with the Huang model as
      the primary model and the cardinal parameters model as the secondary model. The
      results of data analysis showed that the minimum, optimum, and maximum growth
      temperatures of this mutant are 11.5, 36.4, and 44.3  degrees C, and the
      estimated optimum specific growth rate is 0.633 ln CFU/g per h, or 0.275 log
      CFU/g per h. The maximum cell density is 7.84 log CFU/g. The models and kinetic
      parameters were validated using additional isothermal and dynamic growth curves.
      The resulting residual errors of validation followed a Laplace distribution, with
      about 60% of the residual errors within +/-0.5 log CFU/g of experimental
      observations, suggesting that the models could predict the growth of C. botulinum
      LNT01 in ground beef with reasonable accuracy. Comparing with C. perfringens, C.
      botulinum LNT01 grows at much slower rates and with much longer lag times. Its
      growth kinetics is also very similar to C. sporogenes in ground beef. The results
      of computer simulation using kinetic models showed that, while prolific growth of
      C. perfringens may occur in ground beef during cooling, no growth of C. botulinum
      LNT01 or C. sporogenes would occur under the same cooling conditions. The models
      developed in this study may be used for prediction of the growth and risk
      assessments of proteolytic C. botulinum in cooked meats.

PMID- 29580483
TI  - Pre-fermentative cold maceration in presence of non-Saccharomyces strains:
      Evolution of chromatic characteristics of Sangiovese red wine elaborated by
      sequential inoculation.
AB  - Two different Metschnikowia strains (M. pulcherrima MP 346 or M. fructicola MF 98
      3) were applied for the first time, during pre-fermentative cold maceration (PCM)
      in order to enhance the properties and stability of Sangiovese wine color. During
      the 2014 and 2015 vintages a total of eight wines were produced with 24 h of cold
      maceration (PCM 24 h) or 72 h (PCM 72 h), respectively. PCM was carried out in
      presence of MP 346 or MF 98-3 or pectic enzyme (Cuvee Rouge). The sequential
      inoculation of S. cerevisiae strain was carried out at the end of PCM. After 12
      months in the bottle, the MP 346 and MF 98-3 wines contained much higher levels
      of total flavonoids than the Control sample for both vintages and regardless PCM
      duration. Moreover, in both vintages only MF 98-3 showed a higher color intensity
      than the Control sample after 12 months in the bottle. However, neither PCM
      duration nor the microbial/enzymatic treatment increased the level of
      anthocyanins at draining off. Both wines produced by the pre-fermentative
      inoculum with Metschnikowia strains (MP 346 and MF 98-3) retained their red hue,
      regardless the duration of pre-fermentative and fermentative macerations, while
      the Control wines were characterized by faster rates of color loss.

PMID- 29580484
TI  - Optimal characterization of thermal microbial inactivation simulating non
      isothermal processes.

PMID- 29580485
TI  - Application of Raman spectroscopy and chemometric techniques to assess sensory
      characteristics of young dairy bull beef.
AB  - This work aims to develop a rapid analytical technique to predict beef sensory
      attributes using Raman spectroscopy (RS) and to investigate correlations between
      sensory attributes using chemometric analysis. Beef samples (n = 72) were
      obtained from young dairy bulls (Holstein-Friesian and Jersey*Holstein-Friesian)
      slaughtered at 15 and 19 months old. Trained sensory panel evaluation and Raman
      spectral data acquisition were both carried out on the same longissimus thoracis
      muscles after ageing for 21 days. The best prediction results were obtained using
      a Raman frequency range of 1300-2800 cm-1. Prediction performance of partial
      least squares regression (PLSR) models developed using all samples were moderate
      to high for all sensory attributes (R2CV values of 0.50-0.84 and RMSECV values of
      1.31-9.07) and were particularly high for desirable flavour attributes (R2CVs of
      0.80-0.84, RMSECVs of 4.21-4.65). For PLSR models developed on subsets of beef
      samples i.e. beef of an identical age or breed type, significant improvements on
      prediction performances were achieved for overall sensory attributes (R2CVs of
      0.63-0.89 and RMSECVs of 0.38-6.88 for each breed type; R2CVs of 0.52-0.89 and
      RMSECVs of 0.96-6.36 for each age group). Chemometric analysis revealed strong
      correlations between sensory attributes. Raman spectroscopy combined with
      chemometric analysis was demonstrated to have high potential as a rapid and non
      destructive technique to predict the sensory quality traits of young dairy bull
      beef.

PMID- 29580486
TI  - Encapsulation of Hibiscus sabdariffa L. anthocyanins as natural colours in yeast.
AB  - Hibiscus sabdariffa extracts, a rich source of anthocyanin, were subjected to
      encapsulation in yeast cells. An encapsulation yield (EY) of 208 MUg/100 mg of
      cells and an encapsulation efficiency (EE) of 27%, were reached after
      optimisation of the ratios (0.5 g wet yeast cells for 5 ml of anthocyanin
      extracts at 1 g.L-1) and with 10% of ethanol. The storage stability of
      encapsulated pigments was investigated in water and buffer pH 1.5 at 5 & 37 
      degrees C for 10 days and 90  degrees C for 30 min. The percentage of loss of
      colour was determined by colourimetry assays. The microparticles made of yeast
      with or without heat treatment exhibited different protecting effects (P < 0.01).
      At 37  degrees C, the percentage of loss of colour in water was of 2.5% for heat
      treated and 36.5% for non-treated yeast microparticles, suggesting that yeast
      enzymes would be responsible for the loss of anthocyanin during storage. These
      results are confirmed by the percentage of loss of colour which was far lower in
      conditions of low enzymatic activity: 3.1% at 5  degrees C for non-heat-treated
      cells in water. The pH of solvent had also an important effect on the degradation
      of encapsulated anthocyanin; in buffer at pH 1.5 and 37  degrees C with the non
      heat-treated cells, the degradation decreased strongly to 9.4% compared with
      36.5% in water. These results show that yeast cells are a good mean of
      encapsulation of pigments for a colouring purpose and that they provide
      anthocyanins a good protection as long as their enzymes are inactivated.

PMID- 29580487
TI  - Viscoelastic properties of soy protein isolate - pectin blends: Richer than those
      of a simple composite material.
AB  - Concentrated soy protein isolate (SPI) - pectin blends acquire fibrous textures
      by shear-induced structuring while heating. The objective of this study was to
      determine the viscoelastic properties of concentrated SPI-pectin blends under
      similar conditions as during shear-induced structuring, and after cooling. A
      closed cavity rheometer was used to measure these properties under these
      conditions. At 140  degrees C, SPI and pectin had both a lower G* than the blend
      of the two and also showed a different behavior in time. Hence, the viscoelastic
      properties of the blend are richer than those of a simple composite material with
      stable physical phase properties. In addition, the G'pectin was much lower
      compared with the G'SPI and G'SPI-pectin upon cooling, confirming that pectin
      formed a weak dispersed phase. The results can be explained by considering that
      the viscoelastic properties of the blend are influenced by thermal degradation of
      the pectin phase. This degradation leads to: i) release of galacturonic acid, ii)
      lowering of the pH, and iii) water redistribution from the SPI towards the pectin
      phase. The relative importance of those effects are evaluated.

PMID- 29580488
TI  - Biocontrol of Listeria monocytogenes in a meat model using a combination of a
      bacteriocinogenic strain with curing additives.
AB  - The aim of this work was to evaluate the effect of meat curing agents on the
      bioprotective activity of the bacteriocinogenic strain, Enterococcus (E.) mundtii
      CRL35 against Listeria (L.) monocytogenes during meat fermentation. The ability
      of E. mundtii CRL35 to grow, acidify and produce bacteriocin in situ was assayed
      in a meat model system in the presence of curing additives (CA). E. mundtii CRL35
      showed optimal growth and acidification rates in the presence of CA. More
      importantly, the highest bacteriocin titer was achieved in the presence of these
      food agents. In addition, the CA produced a statistical significant enhancement
      of the enterocin CRL35 activity. This positive effect was demonstrated in vitro
      in a meat based culture medium, by time-kill kinetics and finally by using a
      beaker sausage model with a challenge experiment with the pathogenic L.
      monocytogenes FBUNT strain. E. mundtii CRL35 was found to be a promising strain
      of use as a safety adjunct culture in meat industry and a novel functional
      supplement for sausage fermentation, ensuring hygiene and quality of the final
      product.

PMID- 29580489
TI  - Plant cells as food - A concept taking shape.
AB  - Plant cell cultures from cloudberry, lingonberry and stoneberry were studied in
      terms of their nutritional properties as food. Carbohydrate, lipid and protein
      composition, in vitro protein digestibility and sensory properties were
      investigated. Dietary fibre content varied between 21.2 and 36.7%, starch content
      between 0.3 and 1.3% and free sugar content between 17.6 and 33.6%. Glucose and
      fructose were the most abundant sugars. High protein contents between 13.7 and
      18.9% were recorded and all samples had a balanced amino acid profile. In vitro
      protein digestion assay showed hydrolysis by digestive enzymes in fresh cells but
      only limited hydrolysis in freeze-dried samples. The lipid analysis indicated
      that the berry cells were rich sources of essential, polyunsaturated fatty acids.
      In sensory evaluation, all fresh berry cells showed fresh odour and flavour.
      Fresh cell cultures displayed a rather sandy, coarse mouthfeel, whereas freeze
      dried cells melted quickly in the mouth. All in all the potential of plant cells
      as food was confirmed.

PMID- 29580490
TI  - Effect of whey protein isolate films incorporated with montmorillonite and citric
      acid on the preservation of fresh-cut apples.
AB  - The objective of this paper was to evaluate the effect of bioactive whey protein
      isolate/montmorillonite films containing citric acid on the inhibition of
      enzymatic browning and physicochemical properties in minimally processed apples.
      Whey protein isolate films incorporated with montmorillonite (3 g/100 g) and
      citric acid (5 and 10 g/100 g) were applied to the apples slices. All samples
      were packaged in polypropylene trays (14.6 cm * 11.4 cm * 6.5 cm) and stored at 5
      +/- 2  degrees C and 85 +/- 3% RH for eight days. Every two days, the apples
      samples were evaluated for color, acidity, pH, soluble solids, water activity and
      polyphenol oxidase and peroxidase enzyme activity. The enzymatic browning of the
      apples slices was reduced for all films during storage. However, the films
      containing citric acid maintained the color characteristics, reducing the loss of
      quality associated the maintenance of acidity, soluble solids, water activity,
      reduction of polyphenol oxidase and peroxidase activity, thus prolonging the
      shelf life of the apples.

PMID- 29580491
TI  - Application of electrospray ionization mass spectrometry fingerprinting
      associated with macroscopic and histological analysis for Plantago major herbal
      infusions quality control.
AB  - The present study demonstrates the need to conduct an integrative quality control
      of teas marketed as Plantago major. In the present study, quality control checks
      were performed through macroscopic, microscopic and chemical analyses of
      commercial brands. Leaves with parts not allowed for consumption were found in
      all brands. Six brands showed histological similarity <50% with the authentic P.
      major. Eight brands demonstrated low chemical similarity (40 to 60%), indicating
      that they do not have the same compounds from the authentic P. major. All
      commercial samples are contaminated with aflatoxins, indicative of fungicide
      contamination and consequent degradation of phenolic compounds and reduction of
      antioxidant activity from the commercial samples. The difference in the present
      study is the integrative application of methods for success in the quality
      control of P. major, which can be applied to other species. Thus, more rigorous
      inspection actions in the production of teas to guarantee the therapeutic benefit
      of these products.

PMID- 29580492
TI  - Utilisation of water-in-oil-water (W1/O/W2) double emulsion in a set-type yogurt
      model for the delivery of probiotic Lactobacillus paracasei.
AB  - W1/O/W2 emulsion in set-type yogurt has the potential to segregate probiotics in
      order to avoid interference with the starter culture as well as protection
      against harsh processing and digestion conditions. Lactobacillus paracasei subsp.
      paracasei DC 412 probiotic cells in milk-based W1/O/W2 emulsions were
      incorporated in yogurt, in addition to starter cultures Lactobacillus bulgaricus
      and Streptococcus thermophilus, and the effect on the fermentation, bacterial
      growth kinetics, physicochemical properties, and structural characteristics was
      investigated. Stability of W1/O/W2 was monitored with optical microscopy and cryo
      SEM and localisation of encapsulated L. paracasei in yogurt was monitored using
      fluorescent microscopy. During fermentation, starter culture was not affected by
      introduction of L. paracasei and/or W1/O/W2 emulsion. The viability of L.
      paracasei encapsulated in W1/O/W2 emulsion was enhanced during storage and after
      exposure to simulated gastrointestinal conditions. L. paracasei remained within
      the inner W1 phase till the end of the storage period (28 days at 4  degrees C).
      Moreover, W1/O/W2 emulsion altered physicochemical and textural properties;
      however, these were within acceptable range. These results demonstrate the
      capability of W1/O/W2 emulsion to be utilised for probiotic fortification of
      yogurt to increase functionality without interfering with starter culture and
      fermentation.

PMID- 29580493
TI  - Development of LLDPE based active nanocomposite films with nanoclays impregnated
      with volatile compounds.
AB  - In this study, a novel procedure was performed for grafting of nanoclays
      (montmorillonite (MMT) and halloysite (HNT)) with essential oil constituents
      (thymol (THY), eugenol (EUG) and carvacrol (CRV)) using Tween 80 as surfactant
      and then the nanoclay particles were incorporated into LLDPE pellets (5 wt%) to
      produce active nanocomposite films using a twin screw extruder. The resulting
      nanocomposite films were analyzed for antimicrobial and antioxidant capacity as
      well as thickness, mechanical, color, barrier, thermal properties and surface
      morphology and molecular composition. Release of the active compounds from the
      films at the refrigerated and room temperature conditions were also tested. The
      results showed that the films had strong in vitro antibacterial activity against
      pathogenic bacteria (Salmonella Typhimurium, Escherichia coli O157:H7, Listeria
      monocytogenes, Staphylococcus aureus and Bacillus cereus) while their effect
      against lactic acid bacteria (Lactobacillus rhamnosus and Lb. casei) was limited.
      The lowest and highest DPPH scavenging ability levels were 65.59% and % 87.92,
      belonged to THY-MMT and EUG-MMT, respectively. Release of active compounds at 24 
      degrees C was much more rapid than at 4  degrees C. CRV-HNT and THY-HNT provided
      slower release than the other films. SEM results showed that nanoclays were
      uniformly dispersed in the polymer matrix with exceptional agglomerates.
      Incorporation of the active nanoclays significantly (P > 0.05) improved tensile
      strength and elongation of the films. The results confirmed that LLDPE based
      active nanocomposite films could be successfully produced due to its good
      interaction with MMT and HNT, activated with THY, EUG and CRV.

PMID- 29580494
TI  - Orange juice affects acylcarnitine metabolism in healthy volunteers as revealed
      by a mass-spectrometry based metabolomics approach.
AB  - Citrus juices, especially orange juice, constitute rich sources of bioactive
      compounds with a wide range of health-promoting activities. Data from
      epidemiological and in vitro studies suggest that orange juice (OJ) may have a
      positive impact on lipid metabolism. However, the effect of orange juice intake
      on blood lipid profile is still poorly understood. We have used two different
      blood samples, Dried Blood Spots (DBS) and plasma, to assess the effect of two
      week orange juice consumption in healthy volunteers by a mass-spectrometry based
      metabolomics approach. DBS were analysed by liquid chromatography mass
      spectrometry (LC-MS) and plasma samples were analysed by the gas chromatography
      mass spectrometry (GC-MS). One hundred sixty-nine lipids including acylcarnitines
      (AC), lysophosphatidylcholines (LysoPC), (diacyl- and acyl-alkyl-)
      phosphatidylcholines (PC aa and PC ae) and sphingomyelins (SM) were identified
      and quantified in DBS. Eighteen fatty acids were identified and quantified in
      plasma. Multivariate analysis allowed to identify an increase in C3:1, C5-DC(C6
      OH), C5-M-DC, C5:1-DC, C8, C12-DC, lysoPC18:3, myristic acid, pentadecanoic acid,
      palmitoleic and palmitic acid and a decrease in nervonic acid, C0, C2, C10,
      C10:1, C16:1, C16-OH, C16:1-OH, C18-OH, PC aa C40:4, PC ae C38:4, PC ae C42:3, PC
      ae C42:4 and cholesterol levels after orange juice intake. A two-week period of
      orange juice intake could affect fatty acids beta-oxidation through mitochondrial
      and peroxisomal pathways, leading to an increase of short-chain acylcarnitines
      and a decrease of medium and long-chain acylcarnitines. This is the first report
      analyzing the effect of orange juice intake in healthy volunteers using a dried
      blood spot-based metabolomics approach.

PMID- 29580495
TI  - Isolation, molecular and phenotypic characterization of Cronobacter spp. in ready
      to-eat salads and foods from Japanese cuisine commercialized in Brazil.
AB  - The aim of this study was to detect Cronobacter from 30 samples of ready-to-eat
      (RTE) salads and 30 foods from Japanese cuisine as commercially available in
      Brazil. The detection of Cronobacter was as according to the ISO standard
      22964:2017. The isolates were phenotypically characterized by Vitek 2.0 and the
      antibiotic susceptibility profile was determined using the standardized agar disc
      diffusion method. Molecular characterization was accomplished by real-time PCR
      targeting dnaG gene, multiplex-PCR targeting cgcA gene, and fusA allele
      sequencing. Twenty-seven samples (45.0%) contained Cronobacter, 14 (23.3%)
      samples of foods from Japanese cuisine and 13 (21.7%) samples of RTE salads.
      Twenty-nine unique Cronobacter isolates were selected from the 27 positive
      samples and were identified as C. sakazakii (n = 18), C. malonaticus (n = 8), and
      C. dublinensis (n = 3). A high genetic diversity was observed, with 29
      Cronobacter strains being assigned to 11 different fusA alleles, a ratio of 2.6
      strains by fusA allele was found. The cgcA multiplex-PCR failed to identify many
      of the Cronobacter isolates at the species level. Four (13.8%) Cronobacter
      isolates were resistant to one or more antibiotics tested (n = 12). The presence
      of Cronobacter in RTE foods could be a potential threat to human health and
      highlights the need for high levels of hygiene, particularly when preparing food
      for elderly, immunosuppressed persons or adults with prior underlying pathology.
      Epidemiological surveillance agencies should be aware of the risk that these RTE
      foods may represent, for these groups.

PMID- 29580496
TI  - Evaluation of dry heat treatment of soft wheat flour for the production of high
      ratio cakes.
AB  - An accurate method to heat treat flour samples has been used to quantify the
      effects of heat treatment on flour functionality. A variety of analytical methods
      has been used such as oscillatory rheology, rheomixer, solvent retention capacity
      tests, and Rapid Visco Analysis (RVA) in water and in aqueous solutions of
      sucrose, lactic acid, and sodium carbonate. This work supports the hypothesis
      that heat treatment facilitates the swelling of starch granules at elevated
      temperature. Results furthermore indicated improved swelling ability and
      increased interactions of flour polymers (in particular arabinoxylans) of heat
      treated flour at ambient conditions. The significant denaturation of the proteins
      was indicated by a lack of gluten network formation after severe heat treatments
      as shown by rheomixer traces. Results of these analyses were used to develop a
      possible cake flour specification. A method was developed using response surfaces
      of heat treated flour samples in the RVA using i) water and ii) 50% sucrose
      solution. This can uniquely characterise the heat treatment a flour sample has
      received and to establish a cake flour specification. This approach might be
      useful for the characterisation of processed samples, rather than by baking
      cakes. Hence, it may no longer be needed to bake a cake after flour heat
      treatment to assess the suitability of the flour for high ratio cake production,
      but 2 types of RVA tests suffice.

PMID- 29580497
TI  - Sugar reduction in fruit nectars: Impact on consumers' sensory and hedonic
      perception.
AB  - Sugar sweetened beverages are one of the main sources of added sugar in the diet.
      Therefore, sugar reduction in these products could contribute to the prevention
      of various negative health conditions, such as obesity, diabetes and
      cardiovascular diseases. In this context, the present work aimed to study
      consumer sensory and hedonic perception towards sugar reduction in fruit nectars.
      Five sequential difference thresholds for added sugar in three fruit nectars
      (passion fruit, orange/passion fruit and orange/pomegranate) were determined
      based on consumer perception. In each test, difference thresholds were estimated
      using survival analysis based on the responses of 50 consumers to six paired
      comparison tests. Each pair was composed of two samples, a control nectar and a
      sample that was reduced in added sugar from the control. Consumers were asked to
      try each of the samples in each pair and to indicate which was sweeter. Then,
      consumers' sensory and hedonic perception of nectar samples was evaluated for
      each nectar using a 9-point hedonic scale and a check-all-that-apply question.
      Difference thresholds were estimated in 4.20%-8.14% of the added sugar
      concentration of the nectars. No significant differences in overall liking were
      detected for fruit nectars with 20% sugar reduction. However, large heterogeneity
      in consumer hedonic reaction towards sugar reduction was found, which should be
      taken into account in the design of sugar reduction programs. Consumer hedonic
      reaction towards sugar reduction was product dependent. Results from the present
      work reinforce the idea that gradual sugar reduction in sugar sweetened beverages
      is a feasible strategy that could contribute to reduce the sugar intake of the
      population.

PMID- 29580498
TI  - Chemical properties and oxidative stability of Arjan (Amygdalus reuteri) kernel
      oil as emerging edible oil.
AB  - The oxidative stability, as well as the chemical composition of Amygdalus reuteri
      kernel oil (ARKO), were evaluated and compared to those of Amygdalus scoparia
      kernel oil (ASKO) and extra virgin olive oil (EVOO) during and after holding in
      the oven (170  degrees C for 8 h). The oxidative stability analysis was carried
      out by measuring the changes in conjugated dienes, carbonyl and acid values as
      well as oil/oxidative stability index and their correlation with the antioxidant
      compounds (tocopherol, polyphenols, and sterol compounds). The oleic acid was
      determined as the predominant fatty acid of ARKO (65.5%). Calculated
      oxidizability value and an iodine value of ARKO, ASKO and EVOO were reported as
      3.29 and 3.24, 2.00 and 100.0, 101.4 and 81.9, respectively. Due to the high wax
      content (4.5% and 3.3%, respectively), the saponification number of ARKO and ASKO
      (96.4 and 99.8, respectively) was lower than that of EVOO (169.7). ARKO had the
      highest oxidative stability, followed by ASKO and EVOO. Therefore, ARKO can be
      introduced as a new source of edible oil with high oxidative stability.

PMID- 29580499
TI  - Effect of the luxS gene on biofilm formation and antibiotic resistance by
      Salmonella serovar Dublin.
AB  - Biofilms are communities of bacterial cells that serve to protect them from
      external adverse influences and enhance bacterial resistance to antibiotics and
      sanitizers. Here, we studied the regulatory effects of glucose and sodium
      chloride on biofilm formation in Salmonella serovar Dublin (S. Dublin). To
      analyze expression levels of the quorum sensing gene luxS, we created a luxS
      knockout mutant. Also, antimicrobial resistance, hydrophobicity and autoinducer-2
      (AI-2) activity of both the wild-type (WT) and the mutant strain were
      investigated. Our results revealed that glucose was not essential for S. Dublin
      biofilm formation but had an inhibitory effect on biofilm formation when the
      concentration was over 0.1%. NaCl was found to be indispensable in forming
      biofilm, and it also exerted an inhibitory effect at high concentrations (>1.0%).
      Both the WT and the mutant strains displayed significant MIC growth after biofilm
      formation. An increase of up to 32,768 times in the resistance of S. Dublin in
      biofilm phonotype against antibiotic (ampicillin) compared to its planktonic
      phonotype was observed. However, S. Dublin luxS knockout mutant only showed
      slight differences compared to the WT strain in the antimicrobial tests although
      it displayed better biofilm-forming capacity than the WT strain. The mutant
      strain also exhibited higher hydrophobicity than the WT strain, which was a
      feature related to biofilm formation. The production of the quorum sensing
      autoinducer-2 (AI-2) was significantly lower in the mutant strain than in the WT
      strain since the LuxS enzyme, encoded by the luxS gene, plays an essential role
      in AI-2 synthesis. However, the limited biofilm-forming ability in the WT strain
      indicated AI-2 was not directly related to S. Dublin biofilm formation.
      Furthermore, gene expression analysis of the WT and mutant strains revealed
      upregulation of genes related to biofilm stress response and enhanced resistance
      in the luxS mutant strain, which may provide evidence for the regulatory role of
      the luxS gene in biofilm formation.

PMID- 29580500
TI  - Effect of preheat treatment of milk proteins on their interactions with cyanidin
      3-O-glucoside.
AB  - In this study, the binding of cyanidin-3-O-glucoside (C3G) to preheated milk
      proteins beta-lactoglobulin (beta-Lg) and beta-casein (beta-CN) at 55-90  degrees
      C under pH 3.6 and pH 6.3 was investigated using multi-spectral techniques.
      Fluorescence quenching spectroscopy data showed C3G quenched milk proteins'
      fluorescence strongly. Thermodynamic analysis revealed that C3G bound to beta-Lg
      mainly through hydrogen bonding and hydrophobic interactions, and that their
      binding affinity increased gradually with increasing preheating temperature at pH
      6.3, whereas it decreased at pH 3.6. Hydrogen bonding and van der Waals forces
      played the major roles in the interaction of beta-CN with C3G, their affinity
      decreasing with increasing preheating temperature at both pH values. The
      combination of C3G and preheated beta-Lg at 85  degrees C had the strongest
      binding affinity, with a KA of 14.10 (+/-0.33) * 105 M-1 (pH 6.3, 298 K).
      Preheating of milk proteins did not change their major forces with C3G. Fourier
      transform infrared spectra (FT-IR) results showed that C3G binding altered the
      secondary structures of beta-Lg and beta-CN by reducing the proportion of alpha
      helix and beta-sheet structures and increasing the proportion of random coil and
      turn structures. The structural changes of preheated beta-Lg upon C3G binding
      were more pronounced than that of native beta-Lg, while there was little
      difference between preheated and native beta-CN in their structural changes upon
      C3G binding. These results will be helpful in better understanding the relevance
      of native and preheated milk protein-C3G interactions to the stability of C3G,
      and in promoting its application in the food industry as a natural pigment.

PMID- 29580501
TI  - Extraction and identification of antimicrobial peptides from the Canastra
      artisanal minas cheese.
AB  - Canastra artisanal Minas cheese samples were collected in Minas Gerais - Brazil.
      The samples were evaluated in order to observe the presence of antimicrobial
      peptides during 30 days of ripening. Soluble peptides extracted from the cheeses
      were fractionated by reverse phase liquid chromatography and their fractions
      evaluated for inhibitory action of E. coli. Fractions containing antimicrobial
      activity were analyzed by MALDI-TOF/TOF and then peptides were sequenced and
      identified using MASCOT Daemon coupled with UniProt database. The identified
      peptides were then validated by SCAFFOLD application. The peptides present in
      fractions with antimicrobial activity were RPKHPIKHQ, RPKHPIKHQG, RPKHPIKHQGLPQ
      and RPKHPIKHQGLPQE, HQPHQPLPPT and MHQPHQPLPPT. Peptide sequences PKHPIKHQ,
      RPKHPIKHQG, RPKHPIKHQGLPQ and RPKHPIKHQGLPQE were originated from alphas1-casein
      and are their fragments belonging to Isracidine, which in turn is a well known
      antimicrobial peptide. The HQPHQPLPPT and MHQPHQPLPPT peptides were related to
      beta-casein and were isolated in other studies, but their biological activities
      are still unknown.

PMID- 29580502
TI  - Food grade microemulsion systems: Sunflower oil/castor oil derivative
      ethanol/water. Rheological and physicochemical analysis.
AB  - Microemulsions are thermodynamically stable systems that have attracted
      considerable attention in the food industry as delivery systems for many
      hydrophobic nutrients. These spontaneous systems are highly dependent on
      ingredients and composition. In this work phase diagrams were constructed using
      two surfactants (Kolliphor RH40 and ELP), water, sunflower oil, and ethanol as
      cosurfactant, evaluating their physicochemical properties. Stability of the
      systems was studied at 25 and 60  degrees C, monitoring turbidity at 550 nm for
      over a month to identify the microemulsion region. Conductivity was measured to
      classify between water-in-oil and oil-in-water microemulsions. The phase diagram
      constructed with Kolliphor RH40 exhibited a larger microemulsion area than that
      formulated with Kolliphor ELP. All formulations showed a monomodal droplet size
      distribution with low polydispersity index (<0.30) and a mean droplet size below
      20 nm. Systems with higher water content presented a Newtonian behavior;
      increasing the dispersed phase content produced a weak gel-like structure with
      pseudoplastic behavior under flow conditions that was satisfactorily modeled to
      obtain structural parameters.

PMID- 29580503
TI  - Encapsulation of purple corn and blueberry extracts in alginate-pectin hydrogel
      particles: Impact of processing and storage parameters on encapsulation
      efficiency.
AB  - Purple corn (PC) and blueberry (BB) extracts were encapsulated in alginate-pectin
      hydrogel particles to protect anthocyanins (ACNs) from degradation. Combinations
      of alginate to pectin ratios at 82 to 18% and 43 to 57% and total gum
      concentrations (TGC) at 2.2% and 2.8% TGC were prepared to encapsulate both PC
      and BB ACN. The alginate-pectin hydrogel particles containing PC or BB extracts
      were produced by dripping solution into pH 1.2 buffer. Blueberry extract
      encapsulation efficiency was significantly higher than that of purple corn
      extract due to ACN chemical structure differences and the compatibility between
      the ACN structures and alginate-pectin hydrogel structure at the low pH
      environment. Effect of initial ACN concentration in droplets, particle shape,
      alginate to pectin ratio, TGC, ACN source, and curing bath conditions on
      encapsulation efficiency after curing (EEm) was investigated. The initial ACN
      concentration and particle shape didn't influence the EEm, while the alginate to
      pectin ratio, TGC, ACN source and the pH of the curing bath showed significant
      effect on the EEm. The EEm was improved from 26% to 65% for PC ACN and from 48%
      to 116% for BB ACN by augmenting curing bath with ACN at various concentrations.
      The ACN retention during storage (ARs) in hydrogel particles stored in pH 3.0
      buffer was improved at low temperature and high particle weight to solution
      volume ratio. Higher amount of ACN was retained in the hydrogel particles when
      spherical particles were used. Encapsulation in hydrogel particles significantly
      reduced the anthocyanin photodegradation upon exposure to fluorescence light. The
      degradation of ACN was described with a first-order kinetics with half-life
      values of 630 h for encapsulated PC ACN and 58 h for PC ACN aqueous solution.
      Hydrogel production and subsequent storage conditions can be optimized to
      increase the anthocyanin delivered to human body using the low pH beverages such
      as fruit juices as a delivery vehicle.

PMID- 29580504
TI  - In vitro digestion models suitable for foods: Opportunities for new fields of
      application and challenges.
AB  - In vitro digestion assays simulate the physiological conditions of digestion in
      vivo and are useful tools for studying and understanding changes, interactions,
      as well as the bioaccessibility of nutrients, drugs and non-nutritive compounds.
      The technique is widely used in fields such as nutrition, pharmacology and food
      chemistry. Over the last 40 years, more than 2500 research articles have been
      published using in vitro digestion assays (85% of which have been published in
      the last two decades) to elucidate multiple aspects such as protein
      digestibility, nutrient interactions or the viability of encapsulated
      microorganisms. The most recent trend in the use of this technique involves the
      determination of the antioxidant activity of bioactive compounds after digestion.
      However, the inability to reproduce certain in vivo digestion events, as well as
      the multiple models of in vitro digestion, point to a need to optimize and
      validate the method with in vivo assays to determine its limitations and uses.
      The purpose of this paper is to provide an overview of the current state of the
      art of in vitro digestion models through an analysis of how they have evolved in
      terms of the development of digestion models (parameters, protocols, guidance)
      and taking into consideration the boom in new fields of application.

PMID- 29580505
TI  - The prevalence of Listeria spp. food contamination in Iran: A systematic review
      and meta-analysis.
AB  - Listeria monocytogenes can cause circling disease, encephalitis, meningitis,
      septicemia, and mastitis in dairy cattle. Contamination from the environment can
      contaminate foods with Listeria spp. Consumption of foods containing L.
      monocytogenes can lead to listeriosis in susceptible people (adults with a
      compromised immune system), pregnant women, and infants. The objective of this
      study was to determine the prevalence of Listeria spp. and L. monocytogenes in
      various foods in Iran. We searched PubMed, Science direct, Scopus, Google
      scholar, and Iranian local databases including Iranian scientific information
      database and Magiran for relevant studies up to May 2015 using related keywords.
      In our preliminary search, we retrieved 1344 articles. After removing duplicates
      and reviewing titles/abstracts, 117 articles were considered, out of which, 75
      articles had sufficient quality for inclusion in this meta-analysis. The
      prevalence of Listeria spp. contamination was about 18.3% in poultry, 8.5% in raw
      meat, 14.6% in ready-to-eat (RTE) foods, 10% in sea foods, 7.3% in traditional
      dairy, 3.2% in commercial dairy, and 0.1% in eggs. The findings showed that L.
      monocytogenes was most prevalent in ready to eat (9.2%), seafood (5.1%), poultry
      (5%), traditional dairy (4%), raw meat (2.6%), commercial dairy (1.4%), and egg
      (0.2%), respectively. Furthermore, the presence of L. monocytogenes particularly
      in RTE foods (that are consumed without further heat processing) and under-cooked
      products could be a potential risk for public health. So, contamination should be
      controlled at all levels of the food chain.

PMID- 29580506
TI  - Inoculation of Torulaspora delbrueckii as a bio-protection agent in winemaking.
AB  - In oenology, bio-protection consists in adding bacteria, yeasts or a mixture of
      microorganisms on grape must before fermentation in order to reduce the use of
      chemical compounds such as sulphites. More particularly, non-Saccharomyces yeasts
      are used as a total or partial alternative to sulphites. However, scientific data
      capable of proving the effectiveness of adding these yeasts on grape must is
      lacking. This study reports the analysis of antimicrobial and antioxidant effects
      of one non-Saccharomyces yeast, Torulaspora delbrueckii, inoculated at the
      beginning of the white winemaking process in two Burgundian wineries as an
      alternative to sulphiting. The implantation of the T. delbrueckii strain was
      successful in both wineries and had no impact on fermentation kinetics. Adding T.
      delbrueckii reduced biodiversity during the pre-fermentation stages compared to
      sulphited controls and it also effectively limited the development of spoilage
      microorganisms in the same way as the addition of sulphites. T. delbrueckii could
      protect must and wine from oxidation as demonstrated by the analysis of colour
      and phenolic compounds. This is the first evidence that early addition of T.
      delbrueckii during winemaking can be a microbiogical and chemical alternative to
      sulphites. However, its contribution seems to be matrix dependent.

PMID- 29580507
TI  - Study of two-stage ohmic hydro-extraction of essential oil from Artemisia aucheri
      Boiss.: Antioxidant and antimicrobial characteristics.
AB  - The effect of two-stage ohmic-assisted hydrodistillation (TSOH) on the extraction
      and characteristics of essential oils (EOs) from the Artemisia aucheri Boiss. was
      studied, and the results were compared to conventional hydrodistillation (HD).
      According to the results, the yield of EOs obtained through TSOH was almost 30%
      higher than those extracted by HD in nearly one-quarter of a time used by the HD.
      Scanning electron micrographs of A. aucheri leaves showed almost complete
      eruption of EO glands and their surrounding area in TSOH extraction method, hence
      achieving higher yield. The components of the EOs obtained through TSOH were only
      slightly different from those of HD. GC/MS analysis indicated some differences in
      the quantity of the main components, too. The main components of EOs were
      identified as Thymol, Linalool, Geraniol, Camphor, and 1, 8-Cineole, Davana ether
      and Cis-Davanone. Thymol (~17%) and Cis-Davanone (~23%) were the highest quantity
      in the EOs extracted from TSOH and HD, respectively. The variation of antioxidant
      and antimicrobial activities of the EOs may be attributed to these differences in
      the percentage of the main components. The radical scavenging activity of the EOs
      obtained by TSOH was almost twice that of HD. Based on antimicrobial activity
      assays, the EOs were efficient against S. aureus (a Gram-positive), E. coli (a
      Gram-negative), and S. cerevisiae (yeast). However, the efficacy was higher in
      gram-positive than gram-negative bacteria and yeast. The results indicate TSOH
      has a potential to produce EOs from herbal plants at a faster rate, higher yield,
      being probably more efficient in terms of energy although having similar
      antimicrobial and antioxidant efficacy.

PMID- 29580508
TI  - Hydrolysis of tannins by tannase immobilized onto magnetic diatomaceous earth
      nanoparticles coated with polyaniline.

PMID- 29580509
TI  - Microfiltration and ultra-high-pressure homogenization for extending the shelf
      storage stability of UHT milk.
AB  - Fat separation, gelation or sedimentation of UHT milk during shelf-storage
      represent instability phenomena causing the product rejection by consumers.
      Stability of UHT milk is of increasing concern because access to emerging markets
      currently implies for this product to be stable during shipping and prolonged
      storage, up to 12 months. The role of microfiltration prior to UHT process in
      avoiding or retarding the gelation or sediment formation was studied by comparing
      microfiltered UHT milk to conventional UHT milk. A second trial was set up to
      study the effects of double ultra-high pressure homogenization in delaying the
      cream rising and UHT milk homogenized once at lower pressure was taken as
      control. All milk samples were produced at industrial plant level. Milk packages
      were stored at 22  degrees C, opened monthly for visually inspecting the presence
      of cream layer, gel or sediment and then analysed. Microfiltration markedly
      delayed the formation of both gel particles and sediment, with respect to the
      control, and slowed down the proteolysis in terms of accumulation of peptides
      although no correlation was observed between the two phenomena. The double
      homogenization, also evaluated at ultra-structural level, narrowed the fat
      globule distribution and the second one (400 MPa), performed downstream to the
      sterilization step, disrupted the fat-protein aggregates produced in the first
      one (250 MPa). The adopted conditions avoided the appearance of the cream layer
      in the UHT milk up to 18 months. This study contributes important knowledge for
      developing strategies to delay instability phenomena in UHT milk destined to
      extremely long shelf storage.

PMID- 29580510
TI  - Phenolic-rich jaboticaba (Plinia jaboticaba (Vell.) Berg) extracts prevent high
      fat-sucrose diet-induced obesity in C57BL/6 mice.

PMID- 29580511
TI  - Supercritical CO2 impregnation of PLA/PCL films with natural substances for
      bacterial growth control in food packaging.
AB  - Biodegradable polymers with antibacterial properties are highly desirable
      materials for active food packaging applications. Thymol, a dietary monoterpene
      phenol with a strong antibacterial activity is abundant in plants belonging to
      the genus Thymus. This study presents two approaches for supercritical CO2
      impregnation of poly(lactic acid)(PLA)/poly(epsilon-caprolactone)(PCL) blended
      films to induce antibacterial properties of the material: (i) a batch
      impregnation process for loading pure thymol, and (ii) an integrated
      supercritical extraction-impregnation process for isolation of thyme extract and
      its incorporation into the films, operated in both batch or semi-continuous modes
      with supercritical solution circulation. The PCL content in films, impregnation
      time and CO2 flow regime were varied to maximize loading of the films with thymol
      or thyme extract with preserving films' structure and thermal stability.
      Representative film samples impregnated with thymol and thyme extract were tested
      against Gram (-) (Escherichia coli) and Gram(+) (Bacillus subtilis) model
      strains, by measuring their metabolic activity and re-cultivation after exposure
      to the films. The film containing thymol (35.8 wt%) showed a strong antibacterial
      activity leading to a total reduction of bacterial cell viability. Proposed
      processes enable fast, controlled and organic solvent-free fabrication of the
      PLA/PCL films containing natural antibacterial substances at moderately low
      temperature, with a compact structure and a good thermal stability, for potential
      use as active food packaging materials.

PMID- 29580512
TI  - Synergistic effect of X-ray irradiation and sodium hypochlorite against
      Salmonella enterica serovar Typhimurium biofilms on quail eggshells.
AB  - The present study investigated the synergistic bactericidal effects of combined X
      ray irradiation (0.5, 1.0, 1.5, and 2.0 kGy) and sodium hypochlorite (NaOCl) (50,
      100, 150, 200, and 300 ppm) treatment on the reduction of S. enterica serovar
      Typhimurium ATCC 14028 biofilms on quail eggshells. Additionally, the color
      change of the quail eggshells was measured by hunter color "L" (lightness), "a"
      (red/green), "b" (yellow/blue), and "DeltaE" (total color difference).
      Additionally, the puncture force was tested to evaluate eggshell thickness after
      the combined treatments. The highest biofilm reduction values were observed as
      4.6 log CFU/egg after X-ray (2.0 kGy) and NaOCl (300 ppm) treatment. Moreover,
      the synergistic reduction in values after combined treatment was evaluated, and
      the highest biofilm reduction value was 4.3 log CFU/egg by 2.0 kGy X-ray/50 ppm
      NaOCl (1.47 log higher than the sum of reduction values of the individual
      treatments). The color of the quail eggshell and puncture force were not
      significantly changed by combined treatments (p > 0.05 at both cases).
      Consequently, 2.0 kGy X-ray/50 ppm NaOCl was considered optimal for combination
      treatment for eliminating S. enterica ser. Typhimurium biofilms on eggshell
      without any color or thickness changes. Furthermore, combination treatment could
      be useful for improving microbiological safety in the quail egg industry.

PMID- 29580513
TI  - Food isolate Listeria monocytogenes harboring tetM gene plasmid-mediated
      exchangeable to Enterococcus faecalis on the surface of processed cheese.
AB  - The genetic basis of tetracycline resistance in a food isolate Listeria
      monocytogenes (Lm16) was evaluated. Resistance to tetracycline was associated
      with the presence of the tetM gene in plasmid DNA. The sequence of tetM showed
      100% of similarity with the Enterococcus faecalis sequences found in the EMBL
      database, suggesting that Lm16 received this gene from E. faecalis. Various size
      bands were detected in the DNA plasmid analysis, the largest being approximately
      54.38 kb. Transferability of the tetM gene was achieved in vitro by agar matings
      between Lm16 and E. faecalis JH2-2, proving the potential for the spread of tetM
      by horizontal gene transfer. Furthermore, the conjugation experiments were
      performed on the surface of processed cheese, confirming the transferability in a
      food matrix. PCR assays were used to confirm the identity of E. faecalis and to
      detect the tetM gene in transconjugant bacteria. Additionally, the minimal
      inhibitory concentration for tetracycline and rifampicin and plasmid profiling
      were performed. This is the first report of a food isolate L. monocytogenes
      carrying the tetM gene in plasmid DNA, and it highlights the potential risk of
      spreading antimicrobial resistance genes between different bacteria.

PMID- 29580514
TI  - Addition of sucrose during the blueberry heating process is good or bad?
      Evaluating the changes of anthocyanins/anthocyanidins and the anticancer ability
      in HepG-2 cells.
AB  - The objectives of this study were to evaluate the role of sucrose on the
      stability of anthocyanins during heating and the anticancer effects of
      anthocyanins/anthocyanidins on HepG-2 cells. The anthocyanins extract was heated
      at 70  degrees C, 100  degrees C, and 120  degrees C in the presence of 5%, 10%,
      and 20% sucrose. Total anthocyanin content, anthocyanin/anthocyanidin species,
      and the ability to induce HepG-2 cell apoptosis were evaluated. The results
      indicated that the total anthocyanin content decreased during heating at
      temperatures above 70  degrees C. Anthocyanins were degraded into anthocyanidins
      after heat treatment and the degradation rate positively correlated with
      temperature. The degradation of anthocyanins was inhibited with the addition 5%
      to 20% sucrose. However, sucrose had no protective effect on the total
      anthocyanin content. The anticancer ability of blueberry extract was assayed
      using HepG-2 cells and found to be associated with the concentration of
      anthocyanins. Anthocyanins displayed stronger anticancer activity than
      anthocyanidins and this has not been reported so far.

PMID- 29580515
TI  - Probiotic potential of yeasts isolated from pineapple and their use in the
      elaboration of potentially functional fermented beverages.
AB  - Pineapple (Ananas comosus (L.) Merril) is a tropical fruit rich in nutrients
      characterized by a pleasant taste and widely consumed in several countries. It is
      used to produce juice, jams and wine. In this work, 150 yeasts isolates were
      obtained from peel (18) and spontaneously fermented pineapple pulp (132). The
      probiotic potential of 50 isolates was studied. Survival at pH 2.0, pepsin 3.0
      g/L, and tolerance of bile salts (0.1 and 1% (w/v) were determined as indicators
      of survival potential of the isolates during the passage through the human
      gastrointestinal tract in simulated conditions. The selected isolates were also
      evaluated for their resistance to 6 antibiotics, antimicrobial activity against 6
      pathogenic bacteria and autoaggregation and hydrophobicity properties. Five of
      them survived to gastrointestinal conditions, showed antibiotic resistance and
      autoaggregation properties. They were identified by MALDI-TOF MS and sequencing
      of ITS region as Candida lusitaniae (3) and Meyerozyma caribbica (2). Among these
      isolates, M. caribbica 9 D was evaluated in the production of a fermented
      pineapple beverage. The Saccharomyces cerevisiae var. boulardii was used as
      control, due to the fact that it is the only commercially available probiotic
      yeast. With M. caribbica inoculum, the beverage produced showed higher
      concentrations of residual glucose (24.19 g/L) and fructose (8.67 g/L), lower
      concentration of acetic acid (0.22 g/L); higher total phenolic compounds (196.93
      mg/L), catechin (155.56 mg/L), chlorogenic acid (3.64 mg/L), vanillin (0.18 mg/L)
      and ferulic acid (33.2 mg/L). It was observed that M. caribbica population
      remained stable during refrigerated storage with cell counts greater than 7.00
      log CFU/mL over 21 days. Compared to beverage produced with S. cerevisiae var.
      boulardii, the one produced with M. caribbica presented greater acceptance in the
      sensorial analysis for taste, aroma and general acceptance. The fermented
      pineapple beverage prepared with M. caribbica proved to be a good alternative in
      development of a potential probiotic beverage with different sensory and
      nutritional properties.

PMID- 29580516
TI  - Effect of cellulose nanocrystals from sugarcane bagasse on whey protein isolate
      based films.
AB  - Whey protein isolate (WPI) has been utilized as edible film or food packaging
      material. However, WPI films are hydrophilic due to highly polar amino acids
      which provide a moderate barrier to water vapor and low mechanical properties. To
      overcome these drawbacks, cellulose nanocrystals (CNCs) extracted from sugarcane
      bagasse were incorporated with whey protein. FTIR and TGA were used to confirm
      the changes in chemical structures and to observe the thermal properties,
      respectively. The CNCs had sizes of 200-300 nm and diameters of 20-40 nm using
      TEM and AFM technique, respectively. Different amounts of CNCs (0-8 wt% based on
      WPI) were added into whey protein solution and formed films. The lightness and
      transparency of the films tended to decrease with increasing WPI content. The
      water activity (aw) and water solubility of those films increased, whereas their
      water contact angle values decreased, implying that the film became more
      hydrophilic when the cellulose nanocrystal was added. The addition of CNCs
      increased the tensile strength and Young's modulus and reduced the water vapor
      permeability of WPI-based CNC films. However, the CNCs did not change the oxygen
      permeability of the film. Therefore, the obtained WPI films provided good
      mechanical performance and may be promising as an alternative product for film
      packaging.

PMID- 29580517
TI  - Qualitative carbonyl profile in coffee beans through GDME-HPLC-DAD-MS/MS for
      coffee preliminary characterization.
AB  - In this work, an analytical methodology for volatile carbonyl compounds
      characterization in green and roasted coffee beans was developed. The methodology
      relied on a recent and simple sample preparation technique, gas diffusion
      microextraction for extraction of the samples' volatiles, followed HPLC-DAD-MS/MS
      analysis. The experimental conditions in terms of extraction temperature and
      extraction time were studied. A profile for carbonyl compounds was obtained for
      both arabica and robusta coffee species (green and roasted samples). Twenty-seven
      carbonyl compounds were identified and further discussed, in light of reported
      literature, with different coffee characteristics: coffee ageing, organoleptic
      impact, presence of defective beans, authenticity, human's health implication,
      post-harvest coffee processing and roasting. The applied methodology showed to be
      a powerful analytical tool to be used for coffee characterization as it measures
      marker compounds of different coffee characteristics.

PMID- 29580518
TI  - A different approach for the analysis of grapes: Using the skin as sensing
      element.
AB  - In this work, an alternative method to monitor the phenolic maturity of grapes
      was developed. In this approach, the skins of grapes were used to cover the
      surface of carbon paste electrodes and the voltammetric signals obtained with the
      skin-modified sensors were used to obtain information about the phenolic content
      of the skins. These sensors could easily detect differences in the phenolic
      composition of different Spanish varieties of grapes (Mencia, Prieto Picudo and
      Juan Garcia). Moreover, sensors were able to monitor changes in the phenolic
      content throughout the ripening process from veraison until harvest. Using PLS-1
      (Partial Least Squares), correlations were established between the voltammetric
      signals registered with the skin-modified sensors and the phenolic content
      measured by classical methods (Glories or Total Polyphenol Index). PLS-1 models
      provided additional information about Brix degree, density or sugar content,
      which usually used to establish the harvesting date. The quality of the
      correlations was influenced by the maturation process and the structural and
      mechanical skin properties. Thus the skin sensors fabricated with Juan Garcia and
      Prieto Picudo grapes (that showed faster polyphenolic maturation and a higher
      amount of extractable polyphenols than Mencia), showed good correlations and
      therefore could be used to monitor the ripening.

PMID- 29580519
TI  - Properties of flour films as affected by the flour's source and particle size.
AB  - Wheat (W) and rye flour (R, R1 and R2) films were developed. The rye flours used
      differed in their particle size. R1 and R2 resulted from jet milling of the R
      flour at two different feed rates. The mean particle size of W, R, R1 and R2
      flours was 173.87, 100.91, 54.59 and 35.66 MUm, respectively. Glycerol was used
      as plasticizer at concentrations of 0.5, 0.7 and 1 g/g of flour. Films made from
      mixtures of flours (50:50 w/w) were also studied in the presence of 0.7 g
      glycerol/g of flour. Colour, moisture content, solubility, thickness, viscosity,
      microstructure and mechanical properties were assessed. In most cases the films
      were homogeneous. Film moisture content, thickness, opacity and mechanical
      properties were correlated to glycerol concentration. Particle size was found
      important for the mechanical properties. Wheat films were lighter ([L*] ~ 49) and
      less opaque (135). For both single and composite films, moisture content varied
      from 24 to 35%, solubility from 43.5-58%, opacity from 135 to 371, thickness from
      0.66-0.72 mm and mechanical strength from 0.68-1.7 MPa. All film-forming
      solutions exhibited shear thinning behaviour. Wheat flour dominated most of the
      studied properties in composite films. Rye films were more opaque, with
      relatively high solubility but greater mechanical strength.

PMID- 29580520
TI  - Effect of proteolysis index level on instrumental adhesiveness, free amino acids
      content and volatile compounds profile of dry-cured ham.
AB  - Defective textures in dry-cured ham are a common problem that causes important
      economic losses in the ham industry. An increase of proteolysis during the dry
      cured ham processing may lead to high adhesiveness and consumer rejection of the
      product. Therefore, the influence of proteolysis index (PI) on instrumental
      adhesiveness, free amino acids and volatile profile of dry-cured ham was
      assessed. Two hundred Spanish dry-cured ham units were firstly classified
      according to their PI: low PI (<32%), medium PI (32-36%) and high PI (>36%).
      Instrumental adhesiveness was affected by PI, showing the lowest values in the
      batch with low PI. Significant differences (P < 0.05) among groups were found in
      six amino acids: serine, taurine, cysteine, methionine, isoleucine and leucine.
      The content of leucine, serine, methionine, and isoleucine significantly (P <
      0.05) increased as the proteolysis index rose. However, taurine and cysteine
      content showed an opposite behaviour, reaching the highest values in the dry
      cured hams with low PI. Significant differences (P < 0.001) in the total content
      of volatile compounds among ham groups were observed, with the highest
      concentration in the batch with low PI, and decreasing the concentration as the
      PI increased. Regarding the different chemical families of volatiles, the
      hydrocarbons (the main family), alcohols, aldehydes, ketones and acids were more
      abundant in the hams showing the lowest PI. Esters did not show significant
      differences among the three batches of hams studied. The present study
      demonstrated that, apart from the effect on the adhesiveness, an excessive
      proteolysis seems to be associated with negative effects on the taste and aroma
      of the dry-cured ham.

PMID- 29580521
TI  - Yellow tea (Camellia sinensis L.), a promising Chinese tea: Processing, chemical
      constituents and health benefits.
AB  - Yellow tea, also known as huangcha in Chinese, is a lightly fermented tea unique
      to China. As a rare and precious variety of tea, it has gained increasing
      popularity in recent years because of its pleasant mellow taste and known health
      benefits such as anti-oxidation, anti-inflammation and anti-cancer properties.
      Yellow tea is similar to green tea in many ways. The initial production process
      of both teas is the same, but the production of yellow tea requires additional
      steps. A unique procedure called "sealed yellowing" is always involved in yellow
      tea processing to increase the oxidation level and remove the characteristic
      grassy smell associated with green tea while still preserving its health
      benefits. Compared to other types of teas, yellow tea is much less well-known and
      studied. In this review, the history and classification of yellow tea are
      introduced. The processing procedures, including detailed information about
      "sealed yellowing", are presented. The bioactive chemical compounds common in
      various types of teas or unique to yellow tea are discussed. Finally, future
      needs in research and development of yellow tea are proposed.

PMID- 29580522
TI  - Citrus fruit extracts with carvacrol and thymol eliminated 7-log acid-adapted
      Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes: A
      potential of effective natural antibacterial agents.
AB  - Despite the widespread belief that citrus fruit extracts (CFEs) are
      microbiologically safe due to their acidity, limited bactericidal effect results
      in low applicability as antibacterial agent and outbreaks occurred by acid
      adapted pathogens. Here, we examined the antibacterial effects of CFEs [lime
      (Citrus medica), lemon (Citrus limon), calamansi (Citrus microcarpa)] combined
      with essential oil components (EOCs; carvacrol and thymol) against non-acid
      adapted/acid-adapted Escherichia coli O157:H7, Salmonella Typhimurium, and
      Listeria monocytogenes under 22  degrees C for 5 min. CFEs (<20%) alone or small
      amounts of EOCs (2.0 mM; 0.032%) alone could not inactivate the target bacteria
      effectively. However, combined treatments exhibited marked synergy: CFE + EOCs
      eliminated all the bacteria (>6.9 log CFU/ml). Among the CFEs tested, the highest
      synergism was shown by calamansi, an exotic citrus fruit previously unrecognized
      as an antibacterial agent. Although acid-adaptation improved bacterial survival,
      calamansi (<20%) + EOCs (<0.032%) completely inactivated even the most resistant
      pathogen (E. coli O157:H7). Validation test also showed that all tested
      commercial juice products also eliminated acid-adapted pathogens when used with
      EOCs. Physicochemical analysis of tested CFEs (pH measurement and HPLC analysis
      of components) revealed that low pH and flavanone (hesperidin) did not contribute
      to the synergistic bactericidal effects. Rather, the high citric acid content is
      likely to contribute to the strong synergistic effect with EOCs by damaging
      susceptible bacterial membranes. Sensory scores for CFEs were not altered by
      addition of EOCs at concentrations up to 1.5 mM. This study provides new insight
      into the utility of CFEs with EOCs to improve not only the microbiological safety
      of food products containing CFEs but also their applicability as natural
      antibacterial complex.

PMID- 29580523
TI  - Postprandial lipemia and fecal fat excretion in rats is affected by the calcium
      content and type of milk fat present in Cheddar-type cheeses.
AB  - The aim of this study was to better understand the effect of calcium on the
      bioavailability of milk lipids from a cheese matrix using a rat model. Cheddar
      type cheeses were manufactured with one of three types of anhydrous milk fat,
      control, olein or stearin, and salted with or without CaCl2. The cheeses were fed
      to rats and postprandial lipemia was monitored. Feces were analyzed to quantify
      fatty acids excreted as calcium soaps. Higher calcium concentration in cheese
      caused a higher and faster triacylglycerol peak in blood, except for cheeses
      containing stearin. Furthermore, calcium soaps were more abundant in feces when
      the ingested cheese had been enriched with calcium and when the cheese was
      prepared with stearin. Increased lipid excretion was attributable to the affinity
      of saturated long-chain fatty acids for calcium. Results showed that lipid
      bioaccessibility can be regulated by calcium present in Cheddar cheese. This
      study highlights the nutritional interaction between calcium and lipids present
      in the dairy matrix and confirms its physiological repercussions on fatty acid
      bioavailability.

PMID- 29580524
TI  - Investigation on complex coacervation between fish skin gelatin from cold-water
      fish and gum arabic: Phase behavior, thermodynamic, and structural properties.
AB  - The study is aimed to investigate phase behavior, thermodynamic, and structural
      properties based on complex coacervation between fish skin gelatin (FSG) from
      cold-water fish and gum arabic (GA). Phase separation behavior between FSG and GA
      was investigated as a function of pH through varying mixing ratios from 4:1 to
      1:4 at 25  degrees C and 1.0 wt% of total biopolymer concentration. The turbidity
      of FSG-GA mixture reached the maximum (1.743) at the 1:2 of mixing ratio and
      pHopt 3.5, and stabilized at zero. Then physicochemical properties of FSG-GA
      coacervates at pHopt 3.5 and FSG-GA mixtures at pH 6.0 (>pHc) were evaluated.
      Scanning electron microscope (SEM) and X-ray diffraction (XRD) showed that the
      interactions between FSG and GA occurred at pHopt 3.5 and were very weak at pH
      6.0 (>pHc). The isothermal titration calorimetry (ITC) results including the
      negative Gibbs free energy change (DeltaG = -18.71 +/- 1.300 kJ/mol), binding
      enthalpy (DeltaH = -41.81 +/- 1.300 kJ/mol) and binding entropy (TDeltaS = -23.10
      kJ/mol) indicated that the complexation between FSG and GA was spontaneous and
      driven by negative enthalpy owing to the electrostatic interaction and hydrogen
      bondings. The zeta potential (ZP) of FSG-GA coacervates at pHopt 3.5 was -9.00 +/
      0.79 mV that was not close to electrically neutral, indicating other
      interactions besides electronic interaction. Hydrogen bondings in FSG-GA mixtures
      at pH 6.0 and 3.5 were found to be stronger than pure FSG at pH 6.0 and 3.5 owing
      to that the amide II peaks shifted to high wavenumbers. Electronic interaction
      was proven to exist in FSG-GA mixtures at pH 6.0 through the vanishment of
      asymmetric COO- stretching. However, the electronic interaction in FSG-GA
      coacervates at pHopt 3.5 was obviously stronger than FSG-GA mixtures at pH 6.0,
      resulting from the vanishment of asymmetric and symmetric COO- stretching
      vibration and the positively charged FSG and GA. The intrinsic fluorescence
      represented that the introduction of GA changed the microenvironment of tyrosine
      residues in FSG, which may be owing to the unfolding of the tertiary
      conformation. Moreover, the decrease of pH could promote the formation of random
      coils of FSG through circular dichroism (CD). Therefore the addition of GA into
      FSG and decrease of pH might enhance the conformation freedom of FSG, which would
      bring about favorable entropic effects and contribute to the complexation.

PMID- 29580525
TI  - Assessment of effects of phenolic fractions from leaves and petals of dandelion
      in selected components of hemostasis.
AB  - Aerial parts and roots of Taraxacum officinale (dandelion) have been found to be
      rich sources of polyphenols, including cinnamic acid derivatives, flavonoids and
      triterpenoids, which exert different biological activities, such as anti
      inflammatory, anticancer and antimicrobial. Additionally, the whole plant is
      recognized as safe and well tolerated by humans, with no reported adverse
      effects. Nowadays, dandelion is a commonly available dietary supplement and a
      component of pharmaceutical preparations used for the treatment of bladder,
      liver, and spleen. Nevertheless, the effect of dandelion on blood platelets and
      plasma - components of hemostasis involved in the functioning of a cardiovascular
      system and linked with various cardiovascular diseases, has not been studied yet.
      Thus, the main objective of our in vitro experiments was to examine the anti
      platelet and antioxidant properties of four standardized dandelion phenolic
      fractions, i.e. leaves 50% and 85% methanol fractions, and petals 50% and 85%
      methanol fractions, in blood platelets. Additionally, aforementioned plant
      preparations were investigated for hemostatic activity in plasma, using three
      selected hemostatic parameters: the activated partial thromboplastin time (APTT),
      prothrombin time (PT) and thrombin time (TT). None of the studied dandelion
      fractions, caused the damage of human blood platelets, at the whole tested range.
      The inhibition of lipid peroxidation in platelets treated with H2O2/Fe (the donor
      of OH) was observed for two fractions: leaves and petals 50% fractions, both at
      the dose 50 MUg/mL. Analysis of the effect on the coagulation activity of human
      plasma demonstrated that three fractions: petals 50% fraction, and leaves and
      petals 85% fractions, significantly prolonged the thrombin time, at the whole
      tested range. On the contrary, none of the fractions changed the APTT and the PT.
      The obtained results demonstrate that dandelion preparations, based on aerial
      parts, especially rich in hydroxycinnamic acid derivatives (leaves and petals 50%
      fractions) are promising plant materials exerting both antioxidant and
      anticoagulant activities of the hemostatic system that is beneficial in the
      prevention and treatment of cardiovascular diseases.

PMID- 29580526
TI  - Structuration of lipid bases with fully hydrogenated crambe oil and sorbitan
      monostearate for obtaining zero-trans/low sat fats.
AB  - Several studies have shown that excessive intake of trans and saturated fatty
      acids is associated with an increased risk of cardiovascular disease. In this
      context, the food industry has sought alternatives for the development of healthy
      lipid bases, with higher levels of unsaturated fatty acids, adapting to current
      legislation. The incorporation of structuring agents into liquid oils has proven
      to be a potential alternative for obtaining semi-plastic lipid bases with reduced
      levels of saturated fatty acids. Thus, the objective of this study was to produce
      zero trans fat bases with lower saturated fatty acids levels. Palm oil (PO) was
      used as a zero trans-lipid base reference because of its technological
      functionality. Blends containing different proportions of high oleic sunflower
      oil (HOSO) and PO were prepared as follows: control 100: 0; 80:20; 60:40; 40:60;
      20:80; and 100: 0 PO: HOSO (w/w%), respectively. Then, 3% of fully hydrogenated
      crambe oil (FHCO) and 3% sorbitan monostearate (SMS) were added to the blends as
      structuring agents, forming the structured (S) blends. The addition of HOSO to
      the PO decreased the saturated fatty acids by up to 30.6%, with consequent
      increase of unsaturated fatty acids, especially oleic acid. The joint action of
      the SMS and the FCHO allowed for obtaining structured blends with plastic and
      spreadability characteristics, as well as modifications throughout the
      crystallization process of the original blends.

PMID- 29580527
TI  - Rapid determination of the aromatic compounds methyl-anthranilate, 2'
      aminoacetophenone and furaneol by GC-MS: Method validation and characterization
      of grape derivatives.
AB  - A methodology for the rapid determination of the aromatic compounds methyl
      anthranilate (MA), 2'-aminoacetophenone (2-AAP) and furaneol by GC-MS was
      validated and used to characterize grape juice and wine elaborated with the new
      Brazilian grape varieties cultivated in northeastern Brazil, and Brazilian grape
      nectars. The method presented linearity (R2 ? 0.9952), good accuracy (CV <
      12.9%), recovery (76.6% to 106.3%), limit of detection (23 MUg L-1 to 94 MUg L-1)
      and limit of quantification (96 MUg L-1 to 277 MUg L-1) acceptable in only 20 min
      of running. The methodology was considered satisfactory for the purpose, being a
      simple and rapid method for the determination of these compounds in grape
      derivatives drinks. In the characterization of the nectars the compound that
      stood out was the MA, being its presence attributed to the addition of flavorings
      in these products. It was evidenced a significant contribution of furaneol in the
      aroma of grape juice and wines elaborated with the new Brazilian grape varieties.

PMID- 29580528
TI  - Sorting out the phytoprostane and phytofuran profile in vegetable oils.
AB  - Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are prostaglandin-like
      compounds, contributing to defense signaling and prevention of cellular damage.
      These plant oxylipins result from autoxidation of alpha-linolenic acid (ALA) and
      have been proposed as new bioactive compounds due to their structural analogies
      with isoprostanes (IsoPs) and prostanoids derived from arachidonic acid in
      mammals, which have demonstrated diverse biological activities. The present work
      assesses a wide range of vegetable oils - including extra virgin olive oils (n =
      7) and flax, sesame, argan, safflower seed, grapeseed, and palm oils - for their
      content of PhytoPs and PhytoFs. Flax oil displayed the highest concentrations,
      being notable the presence of 9-epi-9-D1t-PhytoP, 9-D1t-PhytoP, 16-B1-PhytoP, and
      9-L1-PhytoP (7.54, 28.09, 28.67, and 19.22 MUg mL-1, respectively), which
      contributed to a total PhytoPs concentration of 119.15 MUg mL-1, and of ent-16
      (RS)-9-epi-ST-Delta14-10-PhytoF (21.46 MUg mL-1). Palm and grapeseed oils
      appeared as the most appropriate negative controls, given the near absence of
      PhytoPs and PhytoFs (lower than 0.15 MUg mL-1). These data inform on the chance
      to develop nutritional trials using flax and grapeseed oils as food matrices that
      would provide practical information to design further assays intended to
      determine the actual bioavailability/bioactivity in vivo.

PMID- 29580529
TI  - Evaluation of the health benefits of consumption of extruded tannin sorghum with
      unfermented probiotic milk in individuals with chronic kidney disease.
AB  - This study investigated the chemical and nutritional composition of breakfast
      cereal based on whole sorghum, and the effect of its association with unfermented
      probiotic milk on the inflammation and oxidative stress of individuals with
      chronic kidney disease. Extruded sorghum breakfast meal presented higher
      carbohydrate concentration (approximately 71%), followed by protein
      (approximately 11%) and lipid (approximately 0.4%). When compared to extruded
      maize breakfast meal, it presented higher percentage of dietary fiber (p < 0.05),
      and higher content of phenolic compounds and tannin, consequently higher
      antioxidant activity (p < 0.05). Extruded sorghum breakfast cereal combined with
      unfermented probiotic milk decreased the C-reactive protein (p < 0.05) and
      malondialdehyde (p < 0.05) serum levels and increased the total antioxidant
      capacity and superoxide dismutase (p < 0.05) in patients with chronic kidney
      disease. Therefore, the extruded sorghum, source of tannin, anthocyanin, and
      dietary fiber, when consumed with unfermented probiotic milk alleviates the
      inflammation and oxidative stress in patients with chronic kidney disease.

PMID- 29580530
TI  - Gazing behavior reactions of Vietnamese and Austrian consumers to Austrian wafers
      and their relations to wanting, expected and tasted liking.
AB  - Predictability of consumers' food choice based on their gazing behavior using eye
      tracking has been shown and discussed in recent research. By applying this
      observational technique and conventional methods on a specific food product, this
      study aims at investigating consumers' reactions associated with gazing behavior,
      wanting, building up expectations, and the experience of tasting. The tested food
      products were wafers from Austria with hazelnut, whole wheat, lemon and vanilla
      flavors, which are very well known in Austria and not known in Vietnam. 114
      Vietnamese and 128 Austrian participants took part in three sections: The results
      indicate that: i) the gazing behavior parameters are highly correlated in a
      positive way with the wanting-to-try choice; ii) wanting to try is in compliance
      with the expected liking for the Austrian consumer panel only, which is very
      familiar with the products; iii) the expected and tasted liking of the products
      are highly country and product dependent. The expected liking is strongly
      correlated with the tasted liking for the Austrian panel only. Differences
      between the reactions of the Vietnamese and Austrian consumers are discussed in
      detail. The results, which reflect the complex process from gazing for "wanting
      to try" to the expected and tasted liking, are discussed in the context of the
      cognitive theory and food choice habits of the consumers.

PMID- 29580531
TI  - Changes of free-form volatile compounds in pre-treated raisins with different
      packaging materials during storage.
AB  - The aroma profiles of volatile compounds (VOCs) were analyzed by GC/MS in pre
      treated air-dried (PAD) and sun-dried (PSD) raisins during storage. Total 98, 94
      and 81 VOCs were identified in Zixiang Seedless raisins (ZSRs), Centennial
      Seedless raisins (CSRs) and Thompson Seedless raisins (TSRs), respectively.
      During storage, the overall concentrations of VOCs of PSD raisins were higher in
      plastic bag (PB) compared to those in woven bag (WB). Regarding fruity and floral
      aromas, the effect of PAD and PB was significant throughout the storage periods
      (3, 6 and 9 months), however, fatty aroma was higher in PSD raisins due to the
      major contribution of 2,3-butanedione. The main fruity and floral aroma
      contributors were beta-damascenone, limonene, rose oxide, geraniol and ethyl
      hexanoate. This study showed that compounds came from unsaturated fatty acid
      oxidation, glycosidically-derived and grape-derived source were contributed to
      fruity, floral or herbaceous aromas, but Maillard reaction-derived VOCs imparted
      fatty and roasted aromas.

PMID- 29580532
TI  - Changes in levels of phytic acid, lectins and oxalates during soaking and cooking
      of Canadian pulses.
AB  - Raw and processed (soaked or cooked) seeds of peas, lentils, chickpeas, fava
      beans and common beans were studied for their contents of antinutritional factors
      (lectins, phytic acid, total and soluble oxalates), along with soybean as a
      control. Analysis of variance indicated that legume type, treatment and their
      interactive effects were significant on these antinutrients. The raw soybean seed
      was found to contain the highest levels of lectins (692.8 HU/mg), phytic acid
      (22.91 mg/g), total oxalate (370.5 mg/100 g) and soluble oxalate (200.7 mg/100 g)
      among all investigated seeds. Relatively high contents of lectins were detected
      in beans (87.69-88.59 HU/mg) and other pulses ranging from 2.73-11.07 HU/mg.
      Phytic acid in Canadian pulses varied slightly from 8.55-22.85 mg/g. Total
      oxalates were variable, ranging from 244.7-294.0 mg/100 g in peas, 168.6-289.1
      mg/100 g in lentils, 241.5-291.4 mg/100 g in fava beans, 92.2-214.0 mg/100 g in
      chickpeas and 98.86-117.0 mg/100 g in common beans. Approximately 24-72% of total
      oxalate appeared to be soluble in all investigated pulses. Soaking the seeds in
      distilled water significantly decreased the contents of lectins (0.11-5.18%),
      total oxalate (17.40-51.89%) and soluble oxalate (26.66-56.29%), but had no
      impact on phytic acid. The cooking process was found to be more effective in
      reducing levels of all the investigated antinutritional factors, except phytic
      acid in common beans and soybean.

PMID- 29580533
TI  - Product reformulation in the context of nutritional warning labels: Exploration
      of consumer preferences towards food concepts in three food categories.
AB  - The reformulation of the food products available in the marketplace to improve
      their nutritional quality has been identified as one of the most cost-effective
      policies for controlling the global obesity pandemic. Front-of-pack (FOP)
      nutrition labelling is one of the strategies that has been suggested to encourage
      the food industry to reformulate their products. However, the extent to which
      certain FOP labels can encourage product reformulation is dependent on consumer
      reaction. The aim of the present work was to assess consumers' perception towards
      product reformulation in the context of the implementation of nutritional
      warnings, an interpretive FOP nutrition labelling scheme. Three product
      categories were selected as target products: bread, cream cheese and yogurt, each
      associated with high content of one target nutrient. For each category, six
      packages were designed using a 3 * 2 experimental design with the following
      variables: product version (regular, nutrient-reduced and nutrient-free) and
      brand (market leader and non-market leader). A total 306 Uruguayan participants
      completed a choice experiment with 18 choice sets. Reformulated products without
      nutritional warnings were preferred by participants compared to regular products
      with nutritional warnings. No apparent preference for products reformulated into
      nutrient-reduced or nutrient-free product versions was found, although
      differences depended on the product category and the specific reformulation
      strategy. Preference for reformulated products without nutritional warnings was
      more pronounced for non-market leaders. Results from the present work suggest
      that reformulation of foods in the context of the implementation of nutritional
      warnings holds potential to encourage consumers to make more healthful food
      choices and to cause a reduction of their intake of nutrients associated with non
      communicable diseases.

PMID- 29580534
TI  - Assessment of cocoa (Theobroma cacao L.) butter content and composition
      throughout fermentations.
AB  - Cocoa fermentation is a crucial step for the development of cocoa aroma and
      precursors of high quality cocoa and by-products. This bioprocess has been
      studied for years to understand cocoa chemical changes but some matters
      concerning changes in fat content remain that are investigated in this work.
      Changes in the quantity (free and total fat), extractability and composition of
      cocoa butter were assessed in samples from Madagascar, the Dominican Republic and
      Ecuador. Increases in free fat content were highlighted in samples from each
      origin thanks to the use of the 'soxtec' solvent method, which preserves the
      integrity of the butter. A 4.71% increase in free fat was measured in the
      Ecuadorian samples fermented for 144 h. Conversely, total fat content remained
      stable throughout fermentation. Protein and polyphenol contents decreases were
      linked to fat content augmentation by a strong negative interaction. Triglyceride
      and total and linked fatty acid kinetics (0 to 6 days) of the butter remained
      statistically stable during fermentation, as did unsaponifiable matter. The
      origin of fermentation had a predominant and significant impact on composition,
      revealed by PCA. This work underlines and explains the importance of fermentation
      process in improving yield of fat that can be extracted while preserving the
      composition of this cocoa butter. This study highlights an interaction in cocoa
      unfermented or partially fermented beans. This phenomenon causes butter content
      retention but is slowly broken after 72 h fermentation. Therefore, fermentation
      appears to be also necessary to enhance the cocoa butter content extracted from
      the nibs.

PMID- 29580535
TI  - The effect of carrageenan on the acid-induced aggregation and gelation conditions
      of quinoa proteins.

PMID- 29580536
TI  - Physicochemical and textural properties of mozzarella cheese made with konjac
      glucomannan as a fat replacer.
AB  - Konjac glucomannan (KGM) is a natural polysaccharide with several favorable
      nutritional characteristics, and exhibits functional properties as a potential
      fat-replacer in dairy products. In our study, composition, color and browning
      (L*, a* and b* before and after heating), and textural characteristics of low-fat
      and skimmed Mozzarella cheese with KGM (LFKGM and SKKGM) were compared with those
      of full-fat, low-fat and skimmed Mozzarella cheese controls (FFC, LFC and SKC)
      after 0, 7, 14, 21 and 28 days of storage at 4  degrees C. In general, LFKGM and
      SKKGM had similar composition to LFC and SKC, respectively, except that LFKGM had
      higher moisture than LFC and SKKGM had high aw than SKC. The LFKGM and SKKGM had
      higher L* (lightness) than LFC and SKC, respectively, and LFKGM had similar
      whiteness to FFC before and after heating. However, the browning factor was not
      affected by KGM addition. The a* values (greenness) of LFKGM and SKKGM were more
      negative than for LFC and SKC before and after heating. The b* values
      (yellowness) of LFKGM and SKKGM were higher than LFC and SKC, respectively.
      Grated SKKGM exhibited lower firmness than SKC, and LFKGM exhibited higher
      stickiness than LFC. The melted LFKGM and SKKGM had similar resistance and
      stretch quality to LFC and SKC when they were stretched, respectively. The
      changes in the lightness, moisture and firmness as affected by KGM addition in
      the cheeses were more close to those of full-fat cheese compared with the cheeses
      without KGM, indicating KGM would be a potential fat replacer to be used in
      Mozzarella cheese.

PMID- 29580537
TI  - Combined high-power ultrasound and high-pressure homogenization
      nanoemulsification: The effect of energy density, oil content and emulsifier type
      and content.
AB  - Combinations of ultrasound (US) and high-pressure homogenization (HPH) at low
      medium energy densities were studied as alternative processes to individual US
      and HPH to produce Tween 80 and whey protein stabilized nanoemulsions, while
      reducing the energy input. To this aim, preliminary trials were performed to
      compare emulsification efficacy of single and combined HPH and US treatments
      delivering low-medium energy densities. Results highlighted the efficacy of US
      HPH combined process in reducing the energy required to produce nanoemulsions
      stabilized with both Tween 80 and whey protein isolate. Subsequently, the effect
      of emulsifier content (1-3% w/w), oil amount (10-20% w/w) and energy density (47
      175 MJ/m3) on emulsion mean particle diameter was evaluated by means of a central
      composite design. Particles of 140-190 nm were obtained by delivering 175 MJ/m3
      energy density at emulsions containing 3% (w/w) Tween 80 and 10% (w/w) oil. In
      the case of whey protein isolate stabilized emulsions, a reduced emulsifier
      amount (1% w/w) and intermediate energy density (120 MJ/m3) allowed a minimum
      droplet size around 220-250 nm to be achieved. Results showed that, in both
      cases, at least 50% of the energy density should be delivered by HPH to obtain
      the minimum particle diameter.

PMID- 29580538
TI  - Alfalfa but not milk in lamb's diet improves meat fatty acid profile and alpha
      tocopherol content.
AB  - To establish animal feeding recommendations, it is required to quantify whether
      the effects of combining dietary alfalfa and milk on meat composition of light
      lambs are overlapped or independent. This experiment aimed to evaluate the
      separate effects of dietary alfalfa and milk access on the light lamb carcass
      quality (10-11 kg), meat colour, chemical composition, fatty acid profile and
      alpha-tocopherol content. Thirty-two lambs were assigned to one of four
      treatments in a 2 * 2 factorial design. The factors were the inclusion of dietary
      forage (grazed alfalfa vs. concentrate-fed indoors) and lactation length (weaning
      at a target live-weight of 13 kg vs. suckling until slaughter at 22-24 kg).
      Dietary alfalfa but not milk supply improved conjugated linoleic acid isomers
      (CLA), omega-3 fatty acids and alpha-tocopherol contents in lamb meat without
      affecting meat colour attributes. Milk supply affected more the fatty acid
      profile (more saturated) than the alpha-tocopherol content of meat. Thus, dietary
      alfalfa improved CLA, omega-3 fatty acids and alpha-tocopherol content in light
      lamb without affecting the meat colour, whereas lengthening the lactation period
      did not provide benefits in terms of meat colour or healthy nutrient composition.

PMID- 29580539
TI  - One-step ultrasound producing O/W emulsions stabilized by chitosan particles.

PMID- 29580540
TI  - Chemical composition of kale as influenced by dry vermicast, potassium humate and
      volcanic minerals.
AB  - Biofortification using agronomic practices can be used to improve the nutritional
      quality of food crops. Three natural media amendments (dry vermicast, potassium
      (K)-humate and volcanic minerals) were assessed under greenhouse conditions to
      determine the effects on the chemical composition of kale (Brassica oleracea L.
      var. acephala 'Ripbor'). The results indicated that K-humate had low pH, while
      the volcanic minerals had high pH. Plants grown in the dry vermicast amended
      media had the highest levels of macronutrients and micronutrients except for zinc
      and iron. However, the glycolipid: phospholipid ratio was lower in kale plants
      cultivated in dry vermicast compared to plants cultivated in the volcanic
      minerals or K-humate. Conversely, plants cultivated in the dry vermicast had
      enhanced levels of polyunsaturated fatty acids. The omega-3 fatty acid content
      was significantly (P < 0.05) higher in plants cultivated in dry vermicast and
      potassium humate, while the omega-6 fatty acids were unaffected by media
      amendments. Dry vermicast was the most effective at increasing plant tissue oleic
      acid content. The total phenolic content and antioxidant capacity were highest in
      plants treated with K-humate, but lowest in the dry vermicast treated plants. In
      conclusion, dry vermicast proved to be the most effective in enhancing the
      phytochemical composition of kale 'Ripbor'. These results suggest dry vermicast
      could be a potential target natural media amendment for biofortifying kale plants
      during cultivation.

PMID- 29580541
TI  - Wild Lonicera caerulea berry polyphenol extract reduces cholesterol accumulation
      and enhances antioxidant capacity in vitro and in vivo.
AB  - The hypocholesterolemic effect of Lonicera caerulea berry extract rich in
      polyphenols (LCBP) on high cholesterol-induced hypercholesterolemia and
      lipoprotein metabolite changes was examined in Caco-2 cells and rats. Cyanidin-3
      glucoside, catechin, and chlorogenic acid are the major phenolic components of
      LCBP. The cholesterol-reducing effect and antioxidant capacity of these
      components were compared in Caco-2 cells. LCBP (80 MUg/mL) and cyanidin-3
      glucoside, catechin, and chlorogenic acid (50 MUM) were found to be effective (p
      < 0.05). Rats were fed a high cholesterol diet (HCD) with or without LCBP
      supplementation (75, 150, and 300 mg/kg body weight intragastrically once daily)
      for 12 weeks. Compared with the HCD control group, LCBP supplementation at 150
      and 300 mg/kg decreased the levels of TC, TG, and LDL-C, but increased that of
      HDL-C. LCBP treatment promoted greater neutral and acidic sterol excretion (p <
      0.05) and improved the antioxidant capacity of the colon tissue, colon contents,
      and blood. Moreover, trimethylamine N-oxide (TMAO) levels were decreased in serum
      (p < 0.05). NPC1L1, ACAT2, and MTP mRNA and protein expression were reduced and
      ABCG5/8 expression was increased (p < 0.05) after LCBP treatment. Our results
      suggest that LCBP could be used as a functional food for the prevention and
      treatment of diseases related to excessive cholesterol accumulation.

PMID- 29580542
TI  - Characterisation of rheology and microstructures of kappa-carrageenan in ethanol
      water mixtures.
AB  - The effects of ethanol (up to 20 wt%) on the rheological properties and
      structural characteristics of kappa-carrageenan gel were investigated by Field
      Emission Scanning Electron Microscopy (FESEM) and Small Angle X-ray Scattering
      (SAXS). Both the sol-gel and gel-sol transition temperatures shifted to higher
      degree (from 36.8 +/- 0.5 to 52.5 +/- 1.4  degrees C and from 51.2 +/- 0.6 to
      67.0 +/- 0.5  degrees C, respectively) upon 20 wt% ethanol addition (P < 0.05).
      The critical relaxation exponent n and the critical gel strength Sg obtained from
      Winter-Chambon criterion decreased and increased, respectively as the ethanol
      concentration increased. The kappa-carrageenan gel was formed due to the
      formation of fibrillar networks, and the fibrillar density increased upon ethanol
      addition via FESEM. Moreover, upon 20 wt% ethanol addition, the average radius of
      gyration of kappa-carrageenan strand increased from 1.18 +/- 0.03 of control to
      1.55 +/- 0.02 nm by SAXS. A mechanism underlying the effect of ethanol on the
      kappa-carrageenan gelation was proposed based on coil to double helix transition
      followed by the helix aggregation.

PMID- 29580543
TI  - The relevance of supply chain characteristics in GHG emissions: The carbon
      footprint of Maltese juices.
AB  - AIMS: Foods and drinks are major contributors (17%) to the greenhouse gas (GHG)
      emissions caused by private consumption in Europe. The carbon footprint (CF) of a
      certain product expresses the total GHG emissions over its whole life cycle, and
      its calculation for foodstuff is a necessary first step to reduce their
      contribution to global warming. The calculation of the CF of Maltese food
      products is especially relevant for two reasons: the economic characteristics of
      the island, whose food sector is highly dependent on imports, implying longer
      transport distances; and the Maltese electricity production mix, based almost
      exclusively on oil combustion. METHODS AND RESULTS: The CF of ten multi-fruit
      juices marketed in Malta has been determined, covering all the processes from the
      agricultural stage to the distribution of the final products. As a functional
      unit (FU), a 250 ml bottle of packaged product arriving at the retailer has been
      considered. The Maltese orange juice, the only final product in which only local
      ingredients are used, presents the lowest CF (0.50 kgCO2/FU), while the remaining
      ones range from 0.67 kgCO2/FU to 0.80 kgCO2/FU. The major contributor to all the
      CFs is juice processing at the Maltese plant (0.42 kgCO2/FU), mainly due to the
      use of electricity (78%). CONCLUSIONS: The influence of both the electricity mix
      and the Maltese supply chain in the CF of the final products has been
      demonstrated. Alternatives to reduce the impacts of the final products have been
      proposed and evaluated that could lower the average CF of the juices by 32%.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The calculation of the CF of Maltese juices
      represents an innovative case study due to the characteristics of the island, and
      it is expected to act as a first step to lower their environmental impacts.

PMID- 29580544
TI  - High voltage electrical discharges combined with enzymatic hydrolysis for
      extraction of polyphenols and fermentable sugars from orange peels.
AB  - Orange peels are a biomass rich in carbohydrates and polyphenols and
      characterized by their low lignin content. This work focuses on finding the best
      combination between physical and biological treatments to enhance the extraction
      of fermentable sugars and polyphenols. High voltage electrical discharges (HVED)
      (0 to 900 kJ/kg) or enzymatic hydrolysis with Viscozyme(r) L (12 FBGU/g) were
      applied on fresh or defatted orange peels for the extraction of polyphenols and
      fermentable sugars. An HVED energy input of 222 kJ/kg was optimal for the
      extraction of reducing sugars (19 g/100 g DM) and polyphenols (0.7 g/100 g DM).
      However, enzymatic hydrolysis allowed a higher extraction of reducing sugars (50
      g/100 g DM). HVED were then applied prior or simultaneously to enzymatic
      hydrolysis to maximize the extraction of biomolecules from orange peels. Thus,
      the results clearly showed that the HVED pretreatment of orange peels is
      efficient to enhance the accessibility of cellulosic biomass to enzymes. HVED
      (222 kJ/kg) prior to enzymatic hydrolysis (12 FBGU/g), was the most effective
      combination of these two processes to get an intensive extraction of biomolecules
      from orange peels.

PMID- 29580545
TI  - Recent advancements in lactic acid production - a review.

PMID- 29580546
TI  - Use of edible films and coatings in cheese preservation: Opportunities and
      challenges.
AB  - In the last years, there has been a growing interest in the use of edible
      materials in food packaging. The cheese industry is clearly one of the sectors
      where these materials have a good opportunity for application, as shown by the
      recent developments on edible coatings and films for cheese. Edible coatings and
      films, besides its edibility, can be used to reduce weight loss and prevent the
      microbiological spoilage through the control of oxygen and carbon dioxide
      exchange rate and as a carrier of antimicrobial compounds. This review summarizes
      the recent results on edible films and coatings for cheese, the main developments
      and the main future perspectives for the application of these materials in the
      cheese industry.

PMID- 29580547
TI  - Preparation and cellular protection against oxidation of Konjac oligosaccharides
      obtained by combination of gamma-irradiation and enzymatic hydrolysis.
AB  - Konjac glucomannan (KGM) is an important source for preparation of Konjac oligo
      glucomannan (KOG), but high molecular weight and viscosity in KGM inhibited its
      full degradation into KOG. In this study, KOG with a degree of polymerization
      between 2 and 9 was obtained by combining gamma-irradiation and enzymatic
      hydrolysis in high yield. We investigated the protective effect of KOG against
      H2O2 - induced oxidative damage in vitro, using human hepatic cell line (LO2) as
      a cell model. Our results demonstrated that pretreating LO2 with KOG
      significantly increases cellular survival and antioxidant activities of GSH-Px
      and CAT enzymes, and reduces levels of LDH, MDA, intracellular accumulation of
      ROS and Ca2+ concentration within the cell. Marked protective effect against
      oxidative damage, in addition to obtained high yield of KOG, supports its
      potential use as an abundant source of antioxidant. To conclude, our study
      provided a theoretical perspective for future uses of KGM.

PMID- 29580548
TI  - Analysis of an old controversy: The compensation temperature for micellization of
      surfactants.
AB  - The actual significance of the so-called compensation temperature Tc for
      micellization of surfactants is reviewed. It is demonstrated that it is possible
      to obtain as many Tc values as the number of temperature intervals in which the
      dependencies of enthalpy and entropy changes with temperature are analyzed. The
      value of each Tc will be the central value To of each temperature interval. These
      two facts suggest that Tc is simply such experimental To. Thus any physical
      interpretation derived from Tc is unfounded.

PMID- 29580549
TI  - Improving the psychometric properties of dot-probe attention measures using
      response-based computation.
AB  - BACKGROUND AND OBJECTIVES: Abnormal threat-related attention in anxiety disorders
      is most commonly assessed and modified using the dot-probe paradigm; however,
      poor psychometric properties of reaction-time measures may contribute to
      inconsistencies across studies. Typically, standard attention measures are
      derived using average reaction-times obtained in experimentally-defined
      conditions. However, current approaches based on experimentally-defined
      conditions are limited. In this study, the psychometric properties of a novel
      response-based computation approach to analyze dot-probe data are compared to
      standard measures of attention. METHODS: 148 adults (19.19 +/- 1.42 years, 84
      women) completed a standardized dot-probe task including threatening and neutral
      faces. We generated both standard and response-based measures of attention bias,
      attentional orientation, and attentional disengagement. We compared overall
      internal consistency, number of trials necessary to reach internal consistency,
      test-retest reliability (n = 72), and criterion validity obtained using each
      approach. RESULTS: Compared to standard attention measures, response-based
      measures demonstrated uniformly high levels of internal consistency with
      relatively few trials and varying improvements in test-retest reliability.
      Additionally, response-based measures demonstrated specific evidence of anxiety
      related associations above and beyond both standard attention measures and other
      confounds. LIMITATIONS: Future studies are necessary to validate this approach in
      clinical samples. CONCLUSIONS: Response-based attention measures demonstrate
      superior psychometric properties compared to standard attention measures, which
      may improve the detection of anxiety-related associations and treatment-related
      changes in clinical samples.

PMID- 29580550
TI  - Correlation Between Clinical, Histopathologic, and Ultrasound Findings in Focal
      Acral Hyperkeratosis.

PMID- 29580551
TI  - Determination of Dynamical Heterogeneity from Dynamic Neutron Scattering of
      Proteins.
AB  - Motional displacements of hydrogen (H) in proteins can be measured using
      incoherent neutron-scattering methods. These displacements can also be calculated
      numerically using data from molecular dynamics simulations. An enormous amount of
      data on the average mean-square motional displacement (MSD) of H as a function of
      protein temperature, hydration, and other conditions has been collected. H
      resides in a wide spectrum of sites in a protein. Some H are tightly bound to
      molecular chains, and the H motion is dictated by that of the chain. Other H are
      quite independent. As a result, there is a distribution of motions and MSDs of H
      within a protein that is denoted dynamical heterogeneity. The goal of this paper
      is to incorporate a distribution of MSDs into models of the H incoherent
      intermediate scattering function, I(Q,t), that is calculated and observed. The
      aim is to contribute information on the distribution as well as on the average
      MSD from comparison of the models with simulations and experiment. For example,
      we find that simulations of I(Q,t) in lysozyme are well reproduced if the
      distribution of MSDs is bimodal with two broad peaks rather than a single broad
      peak.

PMID- 29580553
TI  - Karyotype classification, clinical manifestations and outcome in 124 Turner
      syndrome patients in China.
AB  - OBJECTIVE: To investigate the karyotype, clinical manifestations and natural and
      therapeutic outcome of Turner syndrome (TS) in China. METHOD: A total of 124 TS
      patients with definite diagnosis were included. Karyotype, main clinical signs,
      sexual development and therapeutic outcome were analyzed. RESULTS: TS karyotype
      was classified in 4 types: monosomy (32.7%), mosaic (15.9%), variant (23.9%) and
      mosaic with variant (27.4%). All patients showed short stature, with mean adult
      height<145cm. Sixteen percent of adolescent patients showed spontaneous breast
      development and 8% spontaneous menstruation. The rate of spontaneous sexual
      development was lowest in the monosomy karyotype. Common signs included cubitus
      valgus and wide breast space in about 50% of patients, epicanthus and skin nevus
      in 30% and webbed neck and shield chest in 10-20%. More than 10% of patients had
      associated heart, kidney or thyroid abnormalities. The rate of kidney
      malformation was highest in the monosomy karyotype. Growth hormone (GH) therapy
      can accelerate growth, with 7.6cm and 6.7cm increase in height in the first and
      second years of therapy respectively, slowing to 5.7cm and 4.1cm in the third and
      fourth years. Treated patients who reached nearly adult height were 10.2cm taller
      than untreated patients. Therapeutic effect correlated with GH therapy duration.
      CONCLUSION: TS patients showed a variety of karyotypes, related to the diversity
      of clinical manifestations and outcomes. Sexual development and adult height were
      poorer in monosomy karyotypes than in other types.

PMID- 29580552
TI  - Evidence for DNA Sequence Encoding of an Accessible Nucleosomal Array across
      Vertebrates.
AB  - Nucleosome-depleted regions around which nucleosomes order following the
      "statistical" positioning scenario were recently shown to be encoded in the DNA
      sequence in human. This intrinsic nucleosomal ordering strongly correlates with
      oscillations in the local GC content as well as with the interspecies and
      intraspecies mutation profiles, revealing the existence of both positive and
      negative selection. In this letter, we show that these predicted nucleosome
      inhibitory energy barriers (NIEBs) with compacted neighboring nucleosomes are
      indeed ubiquitous to all vertebrates tested. These 1 kb-sized chromatin patterns
      are widely distributed along vertebrate chromosomes, overall covering more than a
      third of the genome. We have previously observed in human deviations from neutral
      evolution at these genome-wide distributed regions, which we interpreted as a
      possible indication of the selection of an open, accessible, and dynamic
      nucleosomal array to constitutively facilitate the epigenetic regulation of
      nuclear functions in a cell-type-specific manner. As a first, very appealing
      observation supporting this hypothesis, we report evidence of a strong
      association between NIEB borders and the poly(A) tails of Alu sequences in human.
      These results suggest that NIEBs provide adequate chromatin patterns favorable to
      the integration of Alu retrotransposons and, more generally to various
      transposable elements in the genomes of primates and other vertebrates.

PMID- 29580554
TI  - Paramunity-inducing Factors (PINDs) in dendritic cell (DC) cultures lead to
      impaired antileukemic functionality of DC-stimulated T-cells.
AB  - INTRODUCTION: Paramunity-inducing-Factors (PINDs) consist of
      attenuated/inactivated viruses of various poxvirus-genera, used in veterinary
      medicine as non-antigen-specific, non-immunising stimulators of the innate immune
      system against infectious and malignant diseases. Their danger-signaling
      interactions were tested for their capacity to improve leukemic antigen
      presentation on DC generated from AML-patients' blasts ('DCleu') and DC
      stimulation/activation of antileukemic T-cells. METHODS: We analyzed, whether the
      addition of PINDs during DC cultures (15 healthy, 22 leukemic donors) and mixed
      lymphocyte culture (MLC, n = 15) with autologous (n = 6), allogeneic (n = 2) or T
      cells after stem cell transplantation (SCT; n = 7) would alter the quality and
      quantity of DC, the composition of T-cell-subsets, and/or their antileukemic
      functionality (AF) as studied by FACS and functional Fluorolysis-cytotoxicity
      assays. RESULTS: Effects on 1. DC-cultures: PINDs in DC-cultures lead to
      increased proportions of mature DC and DCleu, but reduced proportions of viable
      and overall, as well as TLR4- and TLR9-expressing DC. 2. MLC: PINDs increased
      early (CD8+) T-cell activation (CD69+), but reduced proportions of effector-T
      cells after MLC 3. AF: Presence of PINDs in DC- and MLC-cultures reduced T-cells'
      as well as innate cells' antileukemic functionality. 4. Cytokine-release profile:
      Supernatants from PIND-treated DC- and MLC-cultures resembled an inhibitory
      microenvironment, correlating with impaired blast lysis. CONCLUSIONS: Our data
      shows that addition of PINDs to DC-cultures and MLC result in a "blast-protective
      capacity" leading to impaired AF, likely due to changes in the composition of T
      /innate effector cells and the induction of an inhibitory microenvironment. PINDs
      might be promising in treating infectious diseases, but cannot be recommended for
      the treatment of AML-patients due to their inhibitory influence on antileukemic
      functionality.

PMID- 29580555
TI  - Laparoscopic assisted repair of Morgagni hernia and extended right colectomy for
      colon cancer.

PMID- 29580556
TI  - Discussion of "Does the implementation of a pediatric appendicitis pathway
      promoting ultrasound work outside of a children's hospital?"

PMID- 29580557
TI  - Outcomes associated with resident involvement in ventral hernia repair: A
      population based study using the NSQIP database.
AB  - INTRODUCTION: This study evaluated the effect of resident involvement on patient
      outcomes following major ventral hernia repair (VHR). METHODS: National Surgical
      Quality Improvement Program database was queried to identify patients with major
      VHR between 2007 and 2010. Patient outcomes were compared based on presence or
      absence of resident in the operating room. RESULTS: Residents participated in 57%
      of the 27,773 identified cases. There was no significant difference in return to
      operating room or 30-day mortality. A higher incidence of superficial surgical
      site infection (SSI) (4.9% vs 3.9%, P = 0.013) and longer operative time (129.2
      vs 99.1 min, P < 0.001) were observed with resident involvement in open inpatient
      cases. We found no evidence of a "July effect" on outcomes. CONCLUSION: Resident
      involvement in VHR has little impact on morbidity, and patients can be reassured
      that resident participation in their care is safe.

PMID- 29580558
TI  - Prevalence and Predictors of Depression Among Patients With Epilepsy, Stroke, and
      Multiple Sclerosis Using the Cleveland Clinic Knowledge Program Within the
      Neurological Institute.
AB  - BACKGROUND: Neurological conditions carry a high risk of depression. Given this
      risk, the Neurological Institute (NI) at Cleveland Clinic has initiated
      systematic screening for depression using the 9-item Patient Health Questionnaire
      9 (PHQ-9) embedded within its electronic medical record and its data capture
      system, the Knowledge Program (KP)1. OBJECTIVE: We sought to (1) estimate the
      prevalence of depression among patients with epilepsy, stroke, and multiple
      sclerosis (MS); (2) identify risk factors for depression within each disease; and
      (3) determine differential risks and predictors across neurological disorders.
      METHODS: The KP1 database provided information on approximately 23,000 visits
      involving 7946 outpatients with epilepsy, stroke, or MS seen in neurology
      specialty clinics. The primary outcome measure was depression as defined as a PHQ
      9 >= 10. RESULTS: Overall, the point prevalence of depression was 29.0%. For
      stroke, epilepsy, and MS, prevalence of depression was 23% (95% CI: 21-25%), 33%
      (95% CI: 31-35%), and 29% (95% CI: 28-30%), respectively. For all 3 conditions,
      increasing disease severity and decreased health-related quality of life were
      independent predictors of depression. In multivariable models, there was a
      significant interaction between age and condition, and condition with disease
      severity. In stroke and MS, increasing age was associated with reduced odds for
      depression, whereas in epilepsy, increasing age was associated with an increased
      odds for depression. CONCLUSIONS: Although depression is common among patients
      with neurological disorders, our data suggest that predictors of depression such
      as age and disease severity varied by condition, supporting important possible
      phenomenological and pathophysiological differences of depression across these
      neurological conditions.

PMID- 29580559
TI  - Microplastics in freshwater systems: A review on occurrence, environmental
      effects, and methods for microplastics detection.
AB  - The continuous increase in synthetic plastic production and poor management in
      plastic waste have led to a tremendous increase in the dumping into our aqueous
      environment. Consequently, microplastics commonly defined as sizes less than 5 mm
      are produced and stay in both seawater and freshwater environment. The presence
      of microplastics as a new type of emerging contaminant has become a great issue
      of concerns from public and government authorities. The sources of microplastics
      to freshwater systems are many with the largest portion from wastewater treatment
      plants. The abundance of microplastics varies with the location, from above 1
      million pieces per cubic meter to less than 1 piece in 100 cubic meters.
      Microplastics can cause several harmful physical effects on humans and living
      organisms through such mechanisms as entanglement and ingestion. The
      microplastics can act as carriers of various toxins such as additives from
      industrial production processes and persistent contaminants by the sorption in
      waters. Those toxins may cause great health problems to humans. A few studies on
      the fishes demonstrated that the microplastics and the associated toxins are bio
      accumulated and cause such problems as intestinal damage and change in metabolic
      profiles. In studies of microplastics, fresh water is first sampled by the nets
      with typical mesh size of 330 MUm for collection of microplastics. After the
      volume reducing process, the samples will then go through the purification
      process including density separation by such inorganic salts as sodium chloride
      and digestion process by oxidizing agents or enzymes. The sequence of these two
      processes (namely purification and digestion) is dependent on the sample type.
      The purified samples can be studied by several analytical methods. The commonly
      used methods for the qualification studies are FTIR spectroscopy, Raman
      spectroscopy, pyrolysis-GC/MS, and liquid chromatography. A tagging method can be
      used in the quantification study. Our literature study finds that there is still
      no universal accepted quantification and qualification tools of microplastics in
      fresh waters. More work is anticipated so as to obtain accurate information on
      microplastics in freshwater, which can then be used for the better assessment of
      the environmental risk.

PMID- 29580560
TI  - Understanding implementation and uptake in the National Health Service Health
      Check Programme.
AB  - OBJECTIVES: We present findings from a national online survey of uptake and
      implementation of the National Health Service Health Check (NHSHC) programme. The
      research aimed to understand national variation in implementation of NHSHCs and
      to explore the relationship between uptake and different components of
      implementation. STUDY DESIGN: The study design was a descriptive online survey.
      METHODS: Data were collected via an online survey between November 2015 and
      August 2016. The survey was distributed nationally to practice managers in the
      Midlands and East of England, South of England, North of England and London via
      local NHSHC leads with the help of the national programme manager. RESULTS:
      Responses were received from 153 participants, half of who were practice managers
      (49.7%). Common components of implementation included using postal invitations
      accompanied by the national leaflet, delivering NHSHCs routinely with other
      appointments, offering NHSHC outside of working hours and taking blood samples
      during the consultation. Meaningful exploration of the relationship between
      uptake and components of implementation was not possible given the inaccuracy of
      self-reported uptake data, which was confirmed by comparison with public health
      data in a subsample (n = 18). The comparison also found that a number of
      practices were reporting more completed health checks than the total number of
      patients invited, which again indicates problems that may have implications for
      uptake figures locally and nationally. CONCLUSIONS: Overall, our findings showed
      considerable variation in the implementation of NHSHCs on a national scale and
      issues with quality of programme uptake data, which has implications for national
      reporting for NHSHC.

PMID- 29580561
TI  - Association between bedtime and self-reported illness among college students: a
      representative nationwide study of China.
AB  - OBJECTIVE: This study was to examine the association between bedtime and self
      reported illness among Chinese college students. METHODS: Participants were
      11,942 students, who were identified through a multistage survey sampling
      process. Sleep and illness status were obtained by self report. Both unadjusted
      and adjusted methods were considered in the analyses. RESULTS: The logistic
      regression model found that late bedtime was positively associated with self
      reported short and long-term illness (OR: 3.70 and 1, 79) after adjusting for
      demographic characteristics, short sleep duration, and mental disorders.
      CONCLUSIONS: This study is the first to find a positive relationship between late
      bedtime and self reported illnesses in China or elsewhere. The findings
      underscore the importance of educating college students about the importance of
      sleep.

PMID- 29580562
TI  - An alternative digital workflow for fabricating a mandibular implant-supported
      complete fixed dental prosthesis with limited restorative space: A clinical
      report.
AB  - This clinical report describes the prosthetic rehabilitation of a patient with a
      mandibular implant-supported complete fixed dental prosthesis with limited
      interocclusal restorative space. The problem was manifested by repeated fractures
      of the acrylic resin teeth and distortion of the supporting framework. The
      definitive restoration included a custom computer-aided design and computer-aided
      manufacturing (CAD-CAM) titanium framework with the lingual cusps and most of the
      occlusal table of the mandibular posterior teeth milled in titanium as part of
      the framework. An esthetic CAD-CAM milled denture base along with teeth was
      bonded over this framework.

PMID- 29580563
TI  - Predictors of health-related quality of life in chronically ill children and
      adolescents over time.
AB  - OBJECTIVE: This study aims at identifying predictors of generic health-related
      quality of life (HRQoL) in chronically ill children and adolescents over time.
      The newly developed computer-adaptive test Kids-CAT was used to assess five
      dimensions of HRQoL. METHODS: Longitudinal data from the Kids-CAT study on
      children and adolescents with asthma, diabetes and juvenile arthritis (n = 248;
      aged 7-17 years) were assessed at three measurement points over six months.
      Individual growth modeling served to investigate effects of sociodemographic,
      disease- and health-related as well as psychosocial factors on HRQoL dimensions
      Physical Well-Being (WB), Psychological WB, Parent Relations, Social Support &
      Peers, and School WB over time. RESULTS: Besides effects of sociodemographic
      variables on HRQoL dimensions Social Support & Peers as well as School WB, we
      found that a longer duration of the disease was associated with better Physical
      WB. Lower scores were found for patients with juvenile arthritis compared to
      those with diabetes in HRQoL dimensions Physical WB and Social Support & Peers.
      Disease control was positively related to Physical and Psychological WB over
      time. Mental health problems were negatively associated with four, and subjective
      health complaints with all five HRQoL dimensions over time. Parental mental
      health was positively related to the patients' HRQoL score in Parent Relations
      over time. CONCLUSIONS: HRQoL as a multidimensional construct is associated with
      a wide range of different factors. Pediatricians should consider potential mental
      health problems and subjective health complaints in their patients. Finally,
      parental HRQoL can affect HRQoL in chronically ill children and adolescents.

PMID- 29580564
TI  - Clinical value of autoantibodies for lupus myelitis and its subtypes: A
      systematic review.
AB  - OBJECTIVE: We conducted a systematic review to investigate the clinical value of
      clinical characteristics and autoantibodies, especially lupus-specific
      antibodies, for lupus myelitis and its subtypes. METHODS: We searched PubMed,
      EMBASE, and ICHUSHI without language restrictions for case reports or series of
      lupus myelitis. We focused on cases reported since 1997, when the revised
      classification criteria for systemic lupus erythematosus were published.
      Associations between patient characteristics including autoantibodies and
      functional outcome, survival, subtypes of myelitis (grey and white matter
      myelitis), and treatment were examined. We attempted to contact authors to
      supplement missing information for analysis. RESULTS: Our search identified 224
      cases from 105 articles. White matter myelitis predicted favorable function (odds
      ratio = 15.18; 99% confidence interval, 3.09-151.31; p < 0.0001). Grey matter
      myelitis was associated with longitudinally extensive transverse myelitis (p <
      0.001) and anti-double-stranded DNA (p = 0.003), and tended to be associated with
      anti-beta2-glycoprotein I (p = 0.011). White matter myelitis tended to be
      associated with optic neuritis and anti-neuromyelitis optica antibodies. Although
      our study might be susceptible to under-reporting of original cases and selection
      bias, we aimed to provide a conservative interpretation by setting the
      statistical significance threshold at p < 0.01. CONCLUSIONS: This systematic
      review confirmed that grey matter myelitis predicted poor functional outcome and
      was associated with longitudinally extensive transverse myelitis and anti-double
      stranded DNA antibodies. White matter myelitis was associated with favorable
      functional outcomes and may partially represent a complication of neuromyelitis
      optica.

PMID- 29580565
TI  - Pleuroparenchymal Fibroelastosis and Silicosis: An Unexpected Association.

PMID- 29580566
TI  - Interventional Pulmonology and Solitary Pulmonary Nodule.

PMID- 29580567
TI  - Association of depression, anxiety and post-traumatic stress disorder with
      migraine: Data from Kosovo.
AB  - INTRODUCTION: Migraine is ranked as the seventh leading cause of disability
      worldwide, and it is characterized by a manifestation of combined neurological,
      gastrointestinal, and autonomic symptoms linked with different provoking factors.
      AIM OF THE STUDY: This study investigates the association between migraine and
      PTSD, depression and anxiety in the Kosovo population during the post-war period.
      MATERIAL AND METHODS: 273 war survivors with headache were enrolled in the study
      and were divided into two groups: 153 individuals with confirmed migraine (the
      study group) and 120 individuals with non-migraine headaches (control group). All
      individuals were evaluated using the ICHD-II 2004 diagnostic criteria for
      migraine, as well as the mini-test for PTSD, MMPI (Minnesota Multiphasic
      Personality Inventory) for psychological evaluation, PAI (Personality Assessment
      Inventory) and Hamilton Scale for Depression. RESULTS: Among migraine patients,
      depressive disorders were present in 27.5% of patients, anxiety was found in
      60.8%, and PTSD was present in 39.2%. While the prominence of depression was not
      different between groups, anxiety was significantly more common (p<0.05) in women
      from the control group. PTSD was significantly more common (p<0.001) in migraine
      patients overall, whereas the difference in PTSD prevalence between women from
      the migraine and control groups came close to significance (p=0.05). Females in
      the migraine group had higher incidences of aura (50% vs. 25.5%), whereas the
      incidence of aura in males in each group was approximately equal (9.8% vs.
      7.84%). CONCLUSION: Based on our data, we can confirm an association between PTSD
      and migraine in a sample of patients from Kosovo.

PMID- 29580568
TI  - Giant intradural cervical spine arteriovenous malformations - A case and review
      of literature.
AB  - INTRODUCTION: Spinal arteriovenous malformations (SAVMs) are very rare and can be
      very challenging to treat since none of the therapeutic options does provide a
      definitive cure to these lesions. We believe that incorporation of intraoperative
      angiography during surgery in a hybrid theatre can help achieve a better cure.
      CASE PRESENTATION: We present a 45 years old woman with three (3) years history
      of weakness and ten (10) days' history of acute pain in right upper extremity.
      Magnetic resonance angiography (MRA) of the cervical segment of spinal cord
      revealed tortuous vascular masses from foramen magnum to the inferior margin of
      fourth cervical (C4) vertebral. Spinal digital subtracting angiography (DSA)
      confirmed vascular malformation at the cervical segment of the spinal cord with
      their origin from bilateral posterior spinal arteries. She was successfully
      operated on with the aid of intraoperative angiography without any neurological
      deficient. CONCLUSION: Spinal angiography is the gold standard for all-inclusive
      assessment of SAVMs. Surgery and endovascular techniques equally have key
      therapeutic valves in treatment of SAVMs but a combination of the two gives a
      more accurate and reliable cure to this disorder.

PMID- 29580569
TI  - Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days
      After Ketamine Administration.
AB  - BACKGROUND: The symptoms of major depressive disorder (MDD) are rapidly
      alleviated by administration of a single dose of the glutamatergic modulator
      ketamine. However, few studies have investigated the potential sustained neural
      effects of this agent beyond immediate infusion. This study used functional
      magnetic resonance imaging to examine the effect of a single ketamine infusion on
      the resting state default mode network (DMN) at 2 and 10 days after a single
      ketamine infusion in unmedicated subjects with MDD as well as healthy control
      subjects (HCs). METHODS: Data were drawn from a double-blind, placebo-controlled
      crossover study of 58 participants (33 with MDD and 25 HCs) who received an
      intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2
      separate test days spaced 2 weeks apart. Eight minutes of functional magnetic
      resonance imaging resting state data was acquired at baseline and at about 2 and
      10 days after both infusions. The DMN was defined using seed-based correlation
      and was compared across groups and scans. RESULTS: In subjects with MDD,
      connectivity between the insula and the DMN was normalized compared with HCs 2
      days postketamine infusion. This change was reversed after 10 days and did not
      appear in either of the placebo scans. Group-specific connectivity differences in
      drug response were observed, most notably in the insula in subjects with MDD and
      in the thalamus in HCs. CONCLUSIONS: Connectivity changes in the insula in
      subjects with MDD suggest that ketamine may normalize the interaction between the
      DMN and salience networks, supporting the triple network dysfunction model of
      MDD.

PMID- 29580571
TI  - Sample Size, Model Robustness, and Classification Accuracy in Diagnostic
      Multivariate Neuroimaging Analyses.

PMID- 29580570
TI  - Increased Alcohol Seeking in Mice Lacking Gpr88 Involves Dysfunctional
      Mesocorticolimbic Networks.
AB  - BACKGOUND: Alcohol use disorder (AUD) is devastating and poorly treated, and
      innovative targets are actively sought for prevention and treatment. The orphan G
      protein-coupled receptor GPR88 is enriched in mesocorticolimbic pathways, and
      Gpr88 knockout mice show hyperactivity and risk-taking behavior, but a potential
      role for this receptor in drug abuse has not been examined. METHODS: We tested
      Gpr88 knockout mice for alcohol-drinking and -seeking behaviors. To gain system
      level understanding of their alcohol endophenotype, we also analyzed whole-brain
      functional connectivity in naive mice using resting-state functional magnetic
      resonance imaging. RESULTS: Gpr88 knockout mice showed increased voluntary
      alcohol drinking at both moderate and excessive levels, with intact alcohol
      sedation and metabolism. Mutant mice also showed increased operant responding and
      motivation for alcohol, while food and chocolate operant self-administration were
      unchanged. Alcohol place conditioning and alcohol-induced dopamine release in the
      nucleus accumbens were decreased, suggesting reduced alcohol reward in mutant
      mice that may partly explain enhanced alcohol drinking. Seed-based voxelwise
      functional connectivity analysis revealed significant remodeling of
      mesocorticolimbic centers, whose hallmark was predominant weakening of prefrontal
      cortex, ventral tegmental area, and amygdala connectional patterns. Also,
      effective connectivity from the ventral tegmental area to the nucleus accumbens
      and amygdala was reduced. CONCLUSIONS: Gpr88 deletion disrupts executive, reward,
      and emotional networks in a configuration that reduces alcohol reward and
      promotes alcohol seeking and drinking. The functional connectivity signature is
      reminiscent of alterations observed in individuals at risk for AUD. The Gpr88
      gene, therefore, may represent a vulnerability/resilience factor for AUD, and a
      potential drug target for AUD treatment.

PMID- 29580572
TI  - Reply to: Sample Size, Model Robustness, and Classification Accuracy in
      Diagnostic Multivariate Neuroimaging Analyses.

PMID- 29580573
TI  - [Benign and malignant giant-cell rich lesions of bone: Pathological diagnosis
      with special emphasis on recent immunohistochemistry and molecular techniques].
AB  - The infiltration by numerous osteoclastic giant cells is a frequent finding in
      bone tumors and pseudo-tumors. Pathologists must integrate clinical and
      radiological data to achieve a correct diagnosis in bone pathology. Benign giant
      cell rich lesions of bone encompass giant cell tumor of bone, aneurysmal bone
      cyst, chondroblastoma, brown tumor and fibrous cortical defect/non-ossifying
      fibroma. Amongst malignant neoplasms, variants of conventional osteosarcoma,
      undifferentiated pleomorphic sarcoma, leiomyosarcoma and bone metastasis must be
      discussed. Recently, new diagnostic markers, antibodies for immuno-histochemistry
      and genetic markers, have been developed and are helpful to diagnose such
      lesions.

PMID- 29580574
TI  - Diabetes and the Kidney: Sweet Dreams.

PMID- 29580575
TI  - Diabetic Kidney Disease (c. 2018).

PMID- 29580576
TI  - The Global Epidemiology of Diabetes and Kidney Disease.
AB  - The prevalence of diabetes is increasing worldwide, with the greatest increases
      occurring in low- and middle-income countries. In most developed countries, type
      2 diabetes is presently the leading cause of end-stage renal disease and also
      contributes substantially to cardiovascular disease. In countries with weaker
      economies type 2 diabetes is rapidly replacing communicable diseases as a leading
      cause of kidney disease and is increasingly competing for scarce health care
      resources. Here, we present a narrative review of the prevalence and incidence of
      diabetes-related kidney disease worldwide. Mortality among those with diabetes
      and kidney disease will also be explored. Given the high morbidity and mortality
      associated with chronic kidney disease, we will also examine the level of
      awareness of this disease among people who have it.

PMID- 29580577
TI  - Competing Risk of Death With End-Stage Renal Disease in Diabetic Kidney Disease.
AB  - The concept of competing risks is particularly relevant to survival analyses of
      diabetic ESRD given the high likelihood of death prior to ESRD. Approaches such
      as Kaplan-Meier curves and Cox regression models operate on the assumption that
      there are no competing risks for the event of interest, yielding uninterpretable
      and generally biased estimates in the presence of competing risks. The cumulative
      incidence function and Fine-Gray regression are more appropriate methodologies
      for survival analysis when competing risks are present. We present an example
      taken from the Action to Control Cardiovascular Risk in Diabetes, a randomized
      trial of people with type 2 diabetes at high risk for cardiovascular disease.
      Participants were stratified according to baseline markers of kidney disease: (1)
      no kidney disease; (2) low estimated glomerular filtration rate; (3)
      microalbuminuria alone; and (4) macroalbuminuria. The macroalbuminuria group had
      the highest risk for ESRD and demonstrated the most marked difference between the
      Kaplan-Meier and cumulative incidence estimator. Cox and Fine-Gray regression
      models yielded similar risk estimates for baseline characteristics, with the
      exception of diabetes duration, which was significant in the Cox but not Fine
      Gray model. We underscore the importance of competing risk methods, particularly
      when the competing risk is common, as is the case in diabetic kidney disease.

PMID- 29580578
TI  - Glycemic Control as Primary Prevention for Diabetic Kidney Disease.
AB  - Improving strategies to prevent the development and progression of CKD is a
      highly desirable outcome for all involved in the care of patients with diabetes.
      This is because CKD is a major factor contributing to morbidly and mortality in
      patients with diabetes. Furthermore, diabetes is the leading cause of ESRD in
      most developed countries. Although tight glucose control is now an established
      modality for preventing the development and progression of albuminuria, evidence
      is now accumulating to suggest that it can also ameliorate glomerular filtration
      rate loss and possibly progression to ESRD. These benefits of intensive glucose
      control appear to be most pronounced when applied to patients with the early
      stages of CKD. Recently, medications that belong to the sodium glucose
      cotransporter-type 2 inhibitor and the glucagon-like peptide-1 receptor analogue
      classes have been shown to reduce progression of CKD in patients with type 2
      diabetes and relatively well-preserved kidney function. Here, we review the
      evidence from observational and interventional clinical studies that link good
      glucose control with the primary prevention of diabetic kidney disease with a
      focus on preventing early glomerular filtration rate loss.

PMID- 29580579
TI  - New Glucose-Lowering Agents for Diabetic Kidney Disease.
AB  - The prevalence of diabetes mellitus is increasing and is associated with a range
      of complications including nephropathy. New antidiabetic agents are sought which
      also have positive effects to diminish diabetic complications. Examples of
      promising new classes of such agents are glucagon-like peptide-1 receptor
      agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2
      inhibitors. In addition to cardiovascular protective effects such as weight loss
      and decreased blood pressure of some of these agents, there is evidence for
      renoprotective effects with these agents. This review elaborates on the main
      results of renoprotective effects of these 3 treatment classes. In conclusion,
      currently available trials have demonstrated renoprotective effects for certain
      glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the
      sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin.
      Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective
      effect. Nevertheless, larger studies with respect to renoprotective effects of
      these 3 drug classes are currently being performed, and thus, no conclusions for
      all of these agents can yet be made.

PMID- 29580580
TI  - Treatment of Diabetic Kidney Disease With Hypertension Control and Renin
      Angiotensin System Inhibition.
AB  - The global incidence and prevalence of diabetes continues to expand due primarily
      to the influences of obesity and the contribution of obesity to the progression
      of type 2 diabetes mellitus. The rising prevalence of type 2 diabetes has driven
      an increase in rates of CKD in the past 3 decades in the United States. In turn,
      so have the rates for complications related to type 2 diabetes including CKD, eg,
      diabetic kidney disease (DKD). Although incident rates for DKD have stabilized in
      the recent years, diabetes continues to be the leading cause of ESRD in the
      United States. The United Kingdom Prospective Diabetes Study data and other
      population-level studies support that lowering blood pressure reduces kidney
      disease and cardiovascular disease in patients with type 2 diabetes. Furthermore,
      strategies targeting renin-angiotensin-aldosterone system interruption have shown
      to improve DKD outcomes to a greater extent than other classes of
      antihypertensive regimens.

PMID- 29580582
TI  - Inflammatory Mechanisms as New Biomarkers and Therapeutic Targets for Diabetic
      Kidney Disease.
AB  - Diabetic kidney disease (DKD) is the leading cause of CKD and end-stage kidney
      disease (ESKD) worldwide. Approximately 30-40% of people with diabetes develop
      this microvascular complication, placing them at high risk of losing kidney
      function as well as of cardiovascular events, infections, and death. Current
      therapies are ineffective for arresting kidney disease progression and mitigating
      risks of comorbidities and death among patients with DKD. As the global count of
      people with diabetes will soon exceed 400 million, the need for effective and
      safe treatment options for complications such as DKD becomes ever more urgent.
      Recently, the understanding of DKD pathogenesis has evolved to recognize
      inflammation as a major underlying mechanism of kidney damage. In turn,
      inflammatory mediators have emerged as potential biomarkers and therapeutic
      targets for DKD. Phase 2 clinical trials testing inhibitors of monocyte
      chemotactic protein-1 chemokine C-C motif-ligand 2 and the Janus kinase/signal
      transducer and activator of transcription pathway, in particular, have produced
      promising results.

PMID- 29580585
TI  - Corrigendum to "DNA Triple Helices: Biological consequences and therapeutic
      potential" [Biochimie 90/8 (2008) 1117-1130].

PMID- 29580581
TI  - Acute Kidney Injury and Progression of Diabetic Kidney Disease.
AB  - Diabetic kidney disease, commonly termed diabetic nephropathy (DN), is the most
      common cause of end-stage kidney disease (ESKD) worldwide. The characteristic
      histopathology of DN includes glomerular basement membrane thickening, mesangial
      expansion, nodular glomerular sclerosis, and tubulointerstitial fibrosis.
      Diabetes is associated with a number of metabolic derangements, such as reactive
      oxygen species overproduction, hypoxic state, mitochondrial dysfunction, and
      inflammation. In the past few decades, our knowledge of DN has advanced
      considerably although much needs to be learned. The traditional paradigm of
      glomerulus-centered pathophysiology has expanded to the tubule-interstitium, the
      immune response and inflammation. Biomarkers of proximal tubule injury have been
      shown to correlate with DN progression, independent of traditional glomerular
      injury biomarkers such as albuminuria. In this review, we summarize mechanisms of
      increased susceptibility to acute kidney injury in diabetes mellitus and the
      roles played by many kidney cell types to facilitate maladaptive responses
      leading to chronic and end-stage kidney disease.

PMID- 29580583
TI  - Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease.
AB  - Although estimated glomerular filtration rate and albuminuria are well
      established biomarkers of diabetic kidney disease (DKD), additional biomarkers
      are needed, especially for the early stages of the disease when both albuminuria
      and estimated glomerular filtration rate may still be in the normal range and are
      less helpful for identifying those at risk of progression. Traditional biomarker
      studies for early DKD are challenging because of a lack of good early clinical
      end points, and most rely on changes in existing imprecise biomarkers to assess
      the value of new biomarkers. There are well-characterized changes in kidney
      structure, however, that are highly correlated with kidney function, always
      precede the clinical findings of DKD and, at preclinical stages, predict DKD
      progression. These structural parameters may thus serve as clinically useful end
      points for identifying new biomarkers of early DKD. In addition, investigators
      are analyzing tissue transcriptomic data to identify pathways involved in early
      DKD which may have associated candidate biomarkers measurable in blood or urine,
      and differentially expressed microRNAs and epigenetic modifications in kidney
      tissue are beginning to yield important observations which may be useful in
      identifying new clinically useful biomarkers. This review examines the emerging
      literature on the use of kidney tissue in biomarker discovery in DKD.

PMID- 29580584
TI  - The Promise of Systems Biology for Diabetic Kidney Disease.
AB  - Diabetic kidney disease (DKD) has a complex and prolonged pathogenesis involving
      many cell types in the kidney as well as extrarenal factors. It is clinically
      silent for many years after the onset of diabetes and usually progresses over
      decades. Given this complexity, a comprehensive and unbiased molecular approach
      is best suited to help identify the most critical mechanisms responsible for
      progression of DKD and those most suited for targeted intervention. Systems
      biological investigations provide such an approach since they examine the entire
      network of molecular changes that occur in a disease process in a comprehensive
      way instead of focusing on a single abnormal molecule or pathway. Systems
      biological studies can also start with analysis of the disease in humans, not in
      animal or cell culture models that often poorly reproduce the changes in human
      DKD. Indeed, in the last decade, systems biological approaches have led to the
      identification of critical molecular abnormalities in DKD and have directly led
      to development of new biomarkers and potential treatments for DKD.

PMID- 29580586
TI  - Paediatric bilateral vocal cord paralysis: our experience.
AB  - : Bilateral vocal cord paralysis (BVCP) is the second most common cause of
      neonatal stridor. The aim of this study was to describe the demographic features,
      aetiology, comorbidities, and management of our patients with BVCP. MATERIAL AND
      METHODS: We conducted a retrospective review of the clinical charts of all
      patients diagnosed with BVCP seen at the Department of Respiratory Endoscopy
      between 2011 and 2015. RESULTS: 47 patients were included. Mean age at diagnosis
      was 1 month and male sex predominated (63%). The aetiology was congenital in 59%
      and acquired in 41% of the infants. The cause was most frequently idiopathic in
      the former group and secondary to postoperative injury in the latter. Overall, 42
      patients (89%) required tracheostomy, without statistically significant
      differences between the causes. Of all the patients, 39% regained vocal-cord
      mobility; 44% of those with congenital BVCP, 31% of those with acquired BVCP and
      62.5% with idiopathic BVCP. In five patients a laryngotracheoplasty was performed
      with a posterior costal cartilage graft and one underwent posterior cordectomy.
      All were decannulated. In one patient vocal-cord lateralization was performed,
      avoiding tracheostomy. CONCLUSION: BVCP was most commonly of congenital cause and
      was mainly idiopathic within this group of patients, with a slight male
      preponderance. A high percentage of patients required tracheostomy. A higher
      recovery rate of vocal-cord mobility was observed in idiopathic BVCP, which
      allowed for successful decannulation. In this series, decannulation was possible
      in all patients that underwent surgery; however, further studies with comparison
      of techniques and objective assessment of swallowing and phonation are necessary.

PMID- 29580587
TI  - Olfactory Disorder Pattern In Patients With Neurological Diseases Excluding
      Psychiatric And Traumatic Aetiologies.
AB  - INTRODUCTION: The most common cause of olfactory ENT disorders are colds and flu,
      chronic sinusitis, allergies and traumatic brain injury. Rarer aetiologies
      include certain neurological, psychiatric and metabolic injuries. TARGET: The aim
      of this paper was to check the sort of olfactory disorders found in people who
      have suffered a brain injury, excluding: cranial traumas, psychiatric diseases,
      epilepsy, Parkinson's and Alzheimer's disease, and synaesthesia. MATERIAL AND
      METHODS: A descriptive study based on 61 patients with diagnoses of various
      neurological injuries, which were tested by BAST-24 olfactometer. The results
      were compared with those of a control group (n= 120). RESULTS: The results show
      major impairment in these patients' olfactory sense. The neurological injury
      patients were able to detect from 60-77% of the odours, while the control group
      were able to detect between 98-100%. The neurological patients were able, at
      best, to identify, 11-32% of the odours correctly, while the control group were
      able to correctly detect between 59 -75%. The differences between odour detection
      and correct identification were statistically significant (p<.05). CONCLUSIONS:
      We concluded: a) Neurological injury, not caused by traumatic brain injury,
      psychiatric disorders or ENT diseases, ranged from 68-89% of the olfactory
      failures. b) We must bear in mind that these sorts of injuries can cause
      olfactory disorders. c) ENT and Neurologists should collaborate in the treatment
      of these disorders.

PMID- 29580588
TI  - Globalization of Perianesthesia Nursing.

PMID- 29580589
TI  - Mary Margo McCaffery.

PMID- 29580590
TI  - Decreasing Postanesthesia Care Unit to Floor Transfer Times to Facilitate Short
      Stay Total Joint Replacements.
AB  - PURPOSE: We describe a process for studying and improving baseline postanesthesia
      care unit (PACU)-to-floor transfer times after total joint replacements. DESIGN:
      Quality improvement project using lean methodology. METHODS: Phase I of the
      investigational process involved collection of baseline data. Phase II involved
      developing targeted solutions to improve throughput. Phase III involved measured
      project sustainability. FINDINGS: Phase I investigations revealed that patients
      spent an additional 62 minutes waiting in the PACU after being designated ready
      for transfer. Five to 16 telephone calls were needed between the PACU and the
      unit to facilitate each patient transfer. The most common reason for delay was
      unavailability of the unit nurse who was attending to another patient (58%).
      Phase II interventions resulted in transfer times decreasing to 13 minutes (79%
      reduction, P < .001). Phase III recorded sustained transfer times at 30 minutes,
      a net 52% reduction (P < .001) from baseline. CONCLUSIONS: Lean methodology
      resulted in the immediate decrease of PACU-to-floor transfer times by 79%, with a
      52% sustained improvement. Our methods can also be used to improve efficiencies
      of care at other institutions.

PMID- 29580591
TI  - A Comparison of Aromatherapy to Standard Care for Relief of PONV and PDNV in
      Ambulatory Surgical Patients.
AB  - PURPOSE: To determine effectiveness of aromatherapy (AT) compared with standard
      care (SC) for postoperative and postdischarge nausea and vomiting (PONV/PDNV) in
      ambulatory surgical patients. DESIGN: Prospective randomized study. METHODS:
      Patients (n = 254) received either SC or AT for PONV and interviewed for
      effectiveness of PDNV. Machine learning methods (eight algorithms) were used to
      evaluate. FINDING: Of patients (64 of 221) that experienced PONV, 52% were in the
      AT group and 48% in the SC group. The majority were satisfied with treatment
      (timely, P = .60; effectiveness, P = .86). Of patients that experienced PDNV,
      treatment was 100% effective in the AT group and 67% in the SC group. The cforest
      algorithm was used to develop a model for predicting PONV with literature-based
      risk factors (0.69 area under the curve). CONCLUSIONS: AT is an effective way to
      manage PONV/PDNV. Gender and age were the most important predictors of PONV.

PMID- 29580592
TI  - Benchmarking the Applicability of Four Methods of Endotracheal Tube Cuff
      Inflation for Optimal Sealing: A Randomized Trial.
AB  - PURPOSE: To assess the comparable applicability of four methods of endotracheal
      tube cuff (ETTc) inflation on the basis of optimal level of intracuff pressure
      and presence of intubation-related complications. DESIGN: Double-blind,
      randomized trial. METHODS: A total of 139 adult surgical patients scheduled to
      undergo nitrous oxide-free general anesthesia were assigned into one of four
      groups according to the method used for ETTc inflation. The cuff pressure and air
      volume applied in each method, and laryngotracheal complications were recorded.
      FINDINGS: The highest and lowest ETTc pressure and air volume values were
      recorded in palpation and minimum leak technique group, respectively.
      Laryngotracheal complaints were maximized in palpation and minimized in minimal
      occlusive volume and minimum leak techniques. CONCLUSIONS: The air-return back
      into the syringe method emerges as an attractive and simple-to-perform
      alternative regarding effective ETTc sealing and low incidence of intubation
      related morbidity when a cuff manometer is not readily available. STUDY
      REGISTRATION: ACTRN12615000699561.

PMID- 29580593
TI  - Multimodal Perioperative Analgesia Regimen to Improve Patient Outcomes After
      Total Knee Arthroplasty: A Multidisciplinary Quality Improvement Project.
AB  - PURPOSE: The primary aim of this quality improvement project was to improve
      mobilization for patients after total knee arthroscopy by developing and
      implementing a standardized, evidence-based, multimodal analgesia regimen and
      patient-educational video. Secondary outcomes included opioid consumption, pain,
      and length of stay. DESIGN: A pre-post implementation design was used to compare
      two independent samples. METHODS: Patients were screened based on inclusion and
      exclusion criteria 1-2 weeks before surgery. The anesthesia provider made the
      final determination for inclusion. Data were collected by retrospective chart
      review. FINDINGS: Following implementation, patients displayed significantly
      improved mobilization, reduced opioid consumption, and reduced length of stay.
      Patient-reported pain scores were similar or significantly lower in the
      postimplementation group. CONCLUSIONS: Variability of patient outcomes was
      reduced, and quality of care was improved by standardizing care and incorporating
      the best available evidence, consistent with organization's resources in the
      nonacademic-affiliated, community hospital setting.

PMID- 29580594
TI  - Efficacy of an Ice Popsicle on Thirst Management in the Immediate Postoperative
      Period: A Randomized Clinical Trial.
AB  - PURPOSE: Perioperative thirst is an intense discomfort with high incidence in the
      immediate postoperative period, but nonetheless, it is highly neglected in
      clinical practice. The purpose of this study was to evaluate the efficacy of an
      ice popsicle compared with water at room temperature for thirst relief in the
      immediate postoperative period in terms of variation in the intensity of the
      initial compared with the final thirst and the satiety reached after an hour of
      evaluation and intervention. DESIGN: A parallel randomized clinical trial was
      used. METHODS: A total of 208 patients in the immediate postoperative period were
      assessed for 1 hour, every 15 minutes. Thirst intensity was assessed initially
      and subsequently; interventions were performed according to the group: (1)
      control group, 10 mL of water at room temperature; and (2) experimental group, 10
      mL ice popsicle. FINDINGS: The ice popsicle was 37.8% (P < .01) more effective
      than water regarding the intensity variation between the initial and final
      thirst. The thirst intensity and number of interventions were different for the
      two groups as from the second moment (P < .01). Regarding not reaching satiety
      after an hour of evaluation and intervention, the relative risk was 41%, the
      relative risk reduction was 59%, the absolute risk reduction was 31%, and the
      number needed to treat was 3.2. CONCLUSIONS: Ice popsicle has greater efficacy
      than water at room temperature for thirst management in the immediate
      postoperative period.

PMID- 29580595
TI  - Comfort Theory in Practice-Nurse Anesthetists' Comfort Measures and Interventions
      in a Preoperative Context.
AB  - PURPOSE: The Comfort Theory proposes a systematic work approach to respond to
      patients' holistic needs. The usefulness of the Comfort Theory in the
      perioperative setting should be investigated. The aim of this study was to
      describe and analyze the nurse anesthetist's comfort measures in the preoperative
      context on the basis of the Comfort Theory DESIGN: Qualitative observational
      study METHODS: Semi-structured, clinical observation data collection in the
      preoperative context and deductive thematic analysis FINDINGS: The nurse
      anesthetist's comfort measures in the preoperative phase in the operating room
      department aim to ensure the patient's needs of relief, ease and transcendence in
      the physical, psycho-spiritual, environmental and socio-cultural contexts
      CONCLUSIONS: The application of the Comfort Theory to daily work in the
      preoperative phase is of value for the nurse anesthetist in becoming more aware
      of the individual holistic needs of the patient and in this way adapting and
      initiating comfort measures and interventions.

PMID- 29580596
TI  - A Survey of Perianesthesia Nursing Electronic Documentation.
AB  - PURPOSE: Electronic health records have become a common part of the
      perianesthesia care workflow, particularly for data gathering and documentation.
      The purpose of this survey of perianesthesia nurses was to examine patterns of
      adoption of electronic health records and their effect on clinical documentation
      and patient care. DESIGN: A survey was sent to nurses who are members of the
      American Society of Perianesthesia Nursing (ASPAN). METHODS: The electronic
      documentation survey was sent to the e-mail addresses of 13,339 ASPAN members
      representing various practice environments across the United States. Results were
      examined through descriptive statistics. FINDINGS: About two thirds (66.02%) of
      the respondents indicated that they could capture 80% of their clinical
      interactions with the patient. Few nurses indicated that adoption of the EHR was
      done using a standardized terminology. Respondents (63.99%) overwhelmingly
      indicated that they spent less time interacting with patients and families
      because of electronic documentation demands. CONCLUSIONS: The results pertaining
      to the impact of the EHR on their practice were fairly mixed with some indication
      that there was greater access to important patient data, but with a trade-off of
      less satisfaction and efficiency. Improvements and evaluation of clinical
      documentation are being done, but ongoing optimization and improvements to the
      EHR based on the knowledge needs of nurses will help realize the promise of
      greater quality, safety, and access to data.

PMID- 29580597
TI  - The Quality of Patient Education in Day Surgery by Adult Patients.
AB  - PURPOSE: The purpose of the study was to describe the quality of patient
      education in day surgery as evaluated by adult patients. DESIGN: Descriptive
      design using survey methodology. METHODS: The data were collected by
      questionnaire and measured the quality and implementation of education resources
      for day surgery patients (n = 600) in a university hospital. The data were
      analyzed statistically using basic and multivariate methods. FINDINGS: The
      implementation of patient education has been done in a patient-centered and goal
      oriented way by half of respondents. Most respondents (81%) were satisfied with
      the interaction in patient education. The education resources were reported as
      good by 77% of respondents. CONCLUSIONS: Health care staff should assess for the
      presence of anxiety as a barrier to the comprehension of information. In
      developing patient education, the professional expertise and skills of health
      care staff in educating patients should be used.

PMID- 29580598
TI  - Patterns of Changes in Patients' Postoperative Recovery From a Short-Term
      Perspective.
AB  - PURPOSE: To explore patterns of changes in patients' postoperative recovery over
      1 month within different surgery groups. DESIGN: A quantitative longitudinal
      survey design was used. METHODS: A standardized questionnaire was used (N = 167
      patients); the postoperative recovery profile for self-assessment of recovery.
      The postoperative recovery profile developed for hospitalized patients contains
      17 items distributed over five dimensions: physical symptoms, physical function,
      psychological function, social function, and activity. FINDINGS: Overall,
      orthopaedic patients perceived a lower recovery than general surgery patients.
      All major surgery groups and subgroups except for joint replacement patients
      indicated significant systematic changes toward lower levels of problems. The
      orthopaedic patients assessed their psychological functioning as impaired, and
      the gastric bypass group was the most recovered. CONCLUSIONS: The patients'
      expectations should be charted initially, and patients should be given realistic
      information to achieve a realistic hope for a good life in the future. A
      patient's recovery trajectory may not start after the surgery is completed.
      Rather, it has already commenced before surgery.

PMID- 29580599
TI  - Anesthetists and Surgeons Predict Postoperative Pain.
AB  - PURPOSE: Nurses, surgeons and anesthetists are responsible for the management of
      postoperative pain. This study aimed to investigate surgeons', surgical
      residents', anesthesiologists', and anesthetic residents' predictions of
      patients' postoperative pain and satisfaction with pain management, compared to
      patients' postoperative ratings. DESIGN: The bias and limits of agreement between
      physician and patient ratings of postoperative pain were compared. METHODS:
      Doctors and patients completed a pain questionnaire (Numeric Rating Scale 11
      point) regarding patients' overall pain, worst pain, and dissatisfaction with
      pain management during the first three days postoperatively. FINDINGS: All
      doctors overestimated the degree of pain. Possible reasons include the efforts of
      the postoperative multidisciplinary team. Surgeons were the most accurate
      regarding patients' worst pain. The limits of agreement for doctor and patient
      ratings were very wide. CONCLUSIONS: Postoperative pain management is better than
      predicted.

PMID- 29580600
TI  - Globalization of Health Service: Sharing of Best Practices in Perianesthesia
      Nursing Care, a Case Study of Cross-Border Institutional Collaboration.
AB  - Healthcare is a global concern among all nations and nursing is a global
      profession as evidenced by the flow of healthcare professionals across
      international boundaries. With English as the language of science and commerce
      and post-colonial influence in domestic healthcare practice and training, many
      former Anglo-speaking colonial settlements become parts of an expansive market
      for health human resources migration. The movement of health personnel mainly
      flows from low and medium income countries to high income countries to sustain
      their health systems. The resulting brain drain adversely impacts a source
      country's health system, leading the World Health Organization to declare global
      health migration as the biggest health threat of the 21st century. This report
      illustrates how an overseas health network achieves its goals of developing
      clinical and management excellence through an international exchange program. The
      provider institution also fulfills its mission of contributing to a more
      balanced, equitable and healthier world.

PMID- 29580601
TI  - Effective Communication Improves Patient Safety.

PMID- 29580602
TI  - PACU Nurse Staffing and Patient Outcomes: The Evidence Is Still Missing.

PMID- 29580603
TI  - Dispatches from Haiti: mental health training in a resource-limited setting.

PMID- 29580604
TI  - Dietary advice for people with severe mental illness.

PMID- 29580605
TI  - The cost of child and adolescent mental health services.

PMID- 29580607
TI  - Julian Leff: changing the face of schizophrenia treatment.

PMID- 29580608
TI  - Mental health in the construction industry.

PMID- 29580609
TI  - Those vanished years-In the Mood for Love.

PMID- 29580610
TI  - Social determinants of mental disorders and the Sustainable Development Goals: a
      systematic review of reviews.
AB  - Mental health has been included in the UN Sustainable Development Goals. However,
      uncertainty exists about the extent to which the major social determinants of
      mental disorders are addressed by these goals. The aim of this study was to
      develop a conceptual framework for the social determinants of mental disorders
      that is aligned with the Sustainable Development Goals, to use this framework to
      systematically review evidence regarding these social determinants, and to
      identify potential mechanisms and targets for interventions. We did a systematic
      review of reviews using a conceptual framework comprising demographic, economic,
      neighbourhood, environmental events, and social and culture domains. We included
      289 articles in the final Review. This study sheds new light on how the
      Sustainable Development Goals are relevant for addressing the social determinants
      of mental disorders, and how these goals could be optimised to prevent mental
      disorders.

PMID- 29580611
TI  - Solving the problem of cannabis quantification.

PMID- 29580612
TI  - Drug evaluation in children 10years after the European pediatric regulation
      current challenges and perspectives.
AB  - The European pediatric regulation, that entered into force in June 2007 with the
      objectives to improve the health of children in Europe, dramatically changed the
      regulatory environment of paediatric drug evaluation in Europe. The recent
      10years European medicines agency (EMA) report showed that the number of
      paediatric trials increased and that 238 new medicines and indications for use in
      children were authorised in the EU. However, results remain constrated and futur
      developments require european collaborations beween all experts in developmental
      pharmacology, drug evaluation and trial conduct, training, all aspects already
      considered in different EU paediatric programs.

PMID- 29580613
TI  - Pharmacoepidemiology in pediatrics: Needs, challenges and future directions for
      research.
AB  - Despite international initiatives to promote clinical research in pediatrics,
      there are still many gaps of knowledge in the use of drugs to treat this specific
      population. When important information cannot be derived only from clinical
      trials, use of available observational research tools is required. In this paper,
      we provide an overview of the particular interest of pharmacoepidemiological
      research into the evaluation of drug effects in children and adolescents. We also
      sought to underline the unique challenges and specific needs regarding this
      research. Implementation of innovative methodologies and expansion of database
      networks to perform necessary studies could further improve performances of
      observational research.

PMID- 29580614
TI  - Off-label and unlicensed drug use in children population.
AB  - INTRODUCTION: Off-label (OL) and unlicensed (UL) drug use is widely developed in
      the pediatric population according to previous reviews published in the early
      2010s. The present study is a narrative review of the literature of OL-UL drug
      use from 2013. METHODS: We performed a literature search of research articles
      assessing OL-UL drug use in children (<18 years-old) published in Medline(r) from
      January 2013 until May 2017. RESULTS: Twenty-seven studies were included. OL drug
      use was defined by inappropriate age, indication, dosage or way of administration
      according to the summary of product characteristics in >80% of studies. UL drug
      used was defined by the use of drugs not licensed in the country or modifications
      of licensed drugs in >70% of studies. Among in- and out-patients, the frequency
      of patients exposed to at least one OL-UL drug ranged from 36.3 to 97.0% and from
      18.6 to 40.2%, respectively. Drug use was categorized as OL mostly due to
      inappropriate age, dosage or indication. OL-UL drug use was the most prevalent in
      newborns (mainly preterms) and pre-school children (aged 2-5years). Various drugs
      were involved, depending on patients' age. Polypharmacy and long hospital stays
      were risk factors for OL-UL drug use. Whether OL-UL drug use leads to a higher
      incidence of adverse drug reactions is a controversial finding. CONCLUSIONS: OL
      UL drug use is frequent in children. A standardized definition of OL-UL drug use
      is needed to better assess its frequency, risk factors and impact.

PMID- 29580616
TI  - Increasing robustness of radial GRASE acquisition for SAR-reduced brain imaging.
AB  - PURPOSE: To improve a radial multi-slice 2D gradient- and spin-echo (GRASE)
      sequence and provide an appropriate image reconstruction technique for SAR
      reduced high-resolution neuroimaging. METHODS: Additional readout gradients per
      radio-frequency (RF) refocusing allow for a reduced number of RF pulses. In this
      way, a specific absorption rate (SAR) reduction is achieved and the application
      at high-field systems becomes more feasible. A phase insensitive image
      reconstruction is proposed to reduce signal dropout artifacts originating from
      opposite readout polarities. In addition, the image reconstruction allows for the
      calculation of images with varying contrast from one measurement. RESULTS:
      Results obtained at 3T and 7T demonstrate a SAR-reduction of at least 66% for a
      single-slice experiment with radial GRASE. The reduced SAR is used for an
      increased spatial coverage without increasing the measurement time. Experiments
      at 3T and 7T showed that the visual image quality is comparable to standard TSE
      and GRASE sequences with the same measurement parameters. Using higher EPI
      factors and the presented image reconstruction, artifact-free images with a
      significant SAR-reduction can be achieved. CONCLUSION: Radial GRASE enables SAR
      reduced acquisitions of high-resolution brain images with different contrasts
      from one measurement and is a promising sequence for high-field neuroimaging.

PMID- 29580615
TI  - [SaO2 and PaO2 mismatch: Do not forget hemoglobinopathy].
AB  - INTRODUCTION: Different clinico-biological parameters are used to estimate the
      amount of oxygen available for the organism. Oxygen saturation measured with
      pulse oxymetry (SpO2), oxygen saturation of arterial blood (SaO2) and oxygen
      partial pressure of the arterial blood (PaO2) are the most commonly used. CASE
      REPORT: We report the case of a patient admitted for investigation of respiratory
      failure in the context of chronic dyspnea of effort. SpO2 and SaO2 were
      decreased, though the PaO2 was normal. This mismatch between oxygen saturation
      and PaO2 led to the diagnosis of hemoglobinopathy (Bassett hemoglobin).
      CONCLUSION: The diagnosis of hemoglobinopathy should be considered in cases of
      oxygen desaturation with normal respiratory and cardiac investigations. There are
      no reasons to prescribe long-term oxygen to these patients.

PMID- 29580617
TI  - Biocontrol activity of surfactin A purified from Bacillus NH-100 and NH-217
      against rice bakanae disease.
AB  - The potential of the Bacillus genus to antagonize phytopathogens is associated
      with the production of cyclic lipopeptides. Depending upon the type of
      lipopeptide, they may serve as biocontrol agents that are eco-friendly
      alternatives to chemical fertilizers. This study evaluates the biocontrol
      activity of surfactin-producing Bacillus (SPB) strains NH-100 and NH-217 and
      purified surfactin A from these strains against rice bakanae disease.
      Biologically active surfactin fractions were purified by HPLC, and surfactin A
      variants with chain lengths from C12 to C16 were confirmed by LCMS-ESI. In
      hemolytic assays, a positive correlation between surfactin A production and halo
      zone formation was observed. The purified surfactin A had strong antifungal
      activity against Fusarium oxysporum, F. moniliforme, F. solani, Trichoderma
      atroviride and T. reesei. Maximum fungal growth suppression (84%) was recorded at
      2000 ppm against F. moniliforme. Surfactin A retained antifungal activity at
      different pH levels (5-9) and temperatures (20, 50 and 121  degrees C).
      Hydroponic and pot experiments were conducted to determine the biocontrol
      activity of SPB strains and the purified surfactin A from these strains on Super
      Basmati rice. Surfactin production in the rice rhizosphere was detected by LCMS
      ESI at early growth stages in hydroponics experiments inoculated with SPB
      strains. However, the maximum yield was observed with a consortium of SPB strains
      (T4) and purified surfactin A (T5) treatments in the pot experiment. The outcomes
      of the present study revealed that surfactin A significantly reduced rice bakanae
      disease by up to 80%. These findings suggest that purified surfactin A could be
      an effective biocontrol agent against bakanae disease in rice and should be
      incorporated into strategies for disease management.

PMID- 29580618
TI  - Transcriptional control of the phenol hydroxylase gene phe of Corynebacterium
      glutamicum by the AraC-type regulator PheR.
AB  - Corynebacterium glutamicum can degrade phenol by a meta-cleavage pathway, which
      depends on ncgl2588 (phe) of the phe operon encoding phenol hydroxylase. An
      additional gene, ncgl2587 (pheR), is located upstream of phe. The pheR encodes an
      AraC/XylR-type regulator protein with 377 amino acid residues and is transcribed
      in the same direction as phe. Disruption of pheR by homologous recombination
      resulted in the accumulation of phenol in C. glutamicum. PheR demonstrates a low
      type of constitutive expression where phenol induces phe expression. PheR shares
      75% sequence identity with AraC-type regulator of Corynebacterium lubricantis and
      37 conserved residues, characteristic of AraC family, were located. A constructed
      pK18mobsacB-Pphe:lacZ transcriptional fusion plasmid was transformed into the
      wild-type, DeltapheR, and DeltapheR+ strains, and the results indicated that PheR
      activates the expression of phe encoding phenol hydroxylase. Electrophoretic
      mobility shift assay (EMSA) demonstrated a direct interaction of PheR with the
      phe promoter region and binding site of PheR on the Pphe was located 109-bp
      upstream of phe, as indicated by foot printing analysis. Our research provides
      deep insight into PheR expression and its regulatory function on Phe in C.
      glutamicum.

PMID- 29580619
TI  - Plant growth promoting bacteria as an alternative strategy for salt tolerance in
      plants: A review.
AB  - Approximately 5.2 billion hectare agriculture land are affected by erosion,
      salinity and soil degradation. Salinity stress has significantly affecting the
      fertile lands, and therefore possesses a huge impact on the agriculture and
      economy of a country. Salt stress has severe effects on the growth and
      development of plants as well as reducing its yield. Plants are inherently
      equipped with stress tolerance ability to responds the specific type of stress.
      Plants retained specific mechanisms for salt stress mitigation, such as hormonal
      stimulation, ion exchange, antioxidant enzymes and activation of signaling
      cascades on their metabolic and genetic frontiers that sooth the stressed
      condition. Additional to the plant inherent mechanisms, certain plant growth
      promoting bacteria (PGPB) also have specialized mechanism that play key role for
      salt stress tolerance and plant growth promotion. These bacteria triggers plants
      to produce different plant growth hormones like auxin, cytokinine and gibberellin
      as well as volatile organic compounds. These bacteria also produces growth
      regulators like siderophore, which fix nitrogen, solubilize organic and inorganic
      phosphate. Considering the importance of PGPB in compensation of salt tolerance
      in plants, the present study has reviewed the different aspect and mechanism of
      bacteria that play key role in promoting plants growth and yield. It can be
      concluded that PGPB can be used as a cost effective and economical tool for
      salinity tolerance and growth promotion in plants.

PMID- 29580620
TI  - Physiologically distinct subpopulations formed in Escherichia coli cultures in
      response to heat shock.
AB  - Bacteria can form heterogeneous populations containing phenotypic variants of
      genetically identical cells. The heterogeneity of populations can be considered a
      bet-hedging strategy allowing adaptation to unknown environmental changes - at
      least some individual subpopulations or cells might be able to withstand future
      adverse conditions. Using Percoll gradient centrifugation, we demonstrated that
      in an Escherichia coli culture exposed to heat shock at 50  degrees C, two
      physiologically distinct subpopulations were formed. A high-density subpopulation
      (HD50) demonstrated continued growth immediately after its transfer to LB medium,
      whereas the growth of a low-density subpopulation (LD50) was considerably
      postponed. The LD50 subpopulation contained mainly viable but non-culturable
      bacteria and exhibited higher tolerance to sublethal concentrations of
      antibiotics or H2O2 than HD50 cells. The levels of aggregated proteins and main
      molecular chaperones were comparable in both subpopulations; however, a decreased
      number of ribosomes and a significant increase in protein oxidation were observed
      in the LD50 subpopulation as compared with the HD50 subpopulation. Interestingly,
      under anaerobic heat stress, the formation of the HD50 subpopulation was
      decreased and culturability of the LD50 subpopulation was significantly
      increased. In both subpopulations the level of protein aggregates formed under
      anaerobic and aerobic heat stress was comparable. We concluded that the formation
      of protein aggregates was independent of oxidative damage induced by heat stress,
      and that oxidative stress and not protein aggregation limited growth and caused
      loss of LD50 culturability. Our results indicate that heat stress induces the
      formation of distinct subpopulations differing in their ability to grow under
      standard and stress conditions.

PMID- 29580621
TI  - Heat stress-induced reactive oxygen species participate in the regulation of HSP
      expression, hyphal branching and ganoderic acid biosynthesis in Ganoderma
      lucidum.
AB  - Heat stress (HS) is an important environmental factor that affects the growth and
      metabolism of edible fungi, but the molecular mechanism of the heat stress
      response (HSR) remains unclear. We previously reported that HS treatment
      increased the length between two hyphal branches and induced the accumulation of
      ganoderic acid biosynthesis and the gene expression of heat shock proteins (HSPs)
      in Ganoderma lucidum. In this study, we found that HS induced a significant
      increase in the cytosolic ROS concentration, and exogenously added ROS scavengers
      NAC, VC and NADPH oxidase (Nox) inhibitor DPI reduce the cytosolic ROS
      accumulation in G. lucidum. In addition, the phenomena of the increased gene
      expression and increased length between the two hyphal branches and the
      accumulation of GA biosynthesis induced by HS were mitigated. Furthermore, we
      investigated the effects of HS on Nox-silenced strains (NoxABi-10, NoxABi-11 and
      NoxRi-4, NoxRi-7) and found that the level of ROS concentration was lower than
      that in wild-type (WT) strains treated with HS. Additionally, Nox silenced
      strains reduced the HS-induced increase in HSP expression, the length between two
      hyphal branches and GA biosynthesis compared with the WT strain. These data
      indicate that HS-induced ROS participate in the regulation of HSP expression,
      hyphal branching and ganoderic acid biosynthesis in G. lucidum. In addition,
      these findings identified potential pathways linking ROS networks to HSR,
      physiological and metabolic processes in fungi and provide a valuable reference
      for studying the role of ROS in HSR, mycelium growth and secondary metabolites.

PMID- 29580622
TI  - Phospholipases play multiple cellular roles including growth, stress tolerance,
      sexual development, and virulence in fungi.
AB  - Phospholipases are ubiquitous enzymes that hydrolyze phospholipids. Based on the
      cleavage site of the ester linkage in the substrate phospholipids, phospholipases
      are classified into four major types, phospholipase A (PLA), phospholipase B
      (PLB), phospholipase C (PLC), and phospholipase D (PLD), which are further
      classified into various subtypes. Phospholipases hydrolyze phospholipids into
      various signaling products including phosphatidic acid (PA), diacylglycerol
      (DAG), free fatty acids (FFAs), and lyso-phospholipids (LPLs). These signaling
      products regulate numerous processes such as cytoskeletal dynamics, growth,
      homeostasis, membrane remodeling, nutrient acquisition, secretion, signal
      transduction, stress tolerance, sexual development, and virulence in various
      organisms including fungi. Due to these key cellular roles, phospholipases are
      also promising targets in diagnostic and therapeutic applications. In this
      review, we discuss current knowledge about the cellular roles of different
      classes of phospholipases in fungi.

PMID- 29580623
TI  - Phosphorylation of PppA at threonine 253 controls T6SS2 expression and bacterial
      killing capacity in the marine pathogen Vibrio alginolyticus.
AB  - Type VI secretion systems (T6SSs) are multi-protein secretory nano-machines that
      mediate inter-bacterial competition. Vibrio alginolyticus is an abundant gram
      negative marine bacterium that efficiently kills other bacteria with its T6SS2.
      The V. alginolyticus T6SS2 gene cluster encodes a phosphatase, PppA, and a type
      II membrane-spanning Hanks-type threonine kinase, PpkA2, which have been
      implicated in the activation of T6S. Meanwhile, T6SS2 gene expression is under
      the control of quorum sensing. However, the role of PppA in T6SS2 activity is
      unclear. Here, our phosphoproteomic screen identified PppA as a novel PpkA2
      substrate. Phosphorylation at threonine 253 (T253) of PppA is not conserved in
      other bacteria, suggesting that PppA may play a unique role in T6SS2 activation
      in V. alginolyticus. Interestingly, PppA phosphatase activity was modulated by
      the cognate kinase PpkA2, which implied that a homeostasis is required for
      optimal T6S activity. PppA and phosphorylation of PppA at T253 are important for
      T6S activity and T6SS2-mediated bacterial killing. Moreover, PppA and the
      phosphorylation of PppA are also essential for the expression of LuxR, the master
      regulator of quorum sensing, thus augmenting T6SS2 expression. Collectively, our
      data demonstrated that phosphorylation of PppA at T253 controls the activity of
      T6SS2, thereby enhancing the competitive fitness of V. alginolyticus.

PMID- 29580624
TI  - Antidiabetic "gliptins" affect biofilm formation by Streptococcus mutans.
AB  - Streptococcus mutans, a dental caries causing odontopathogen, produces X-prolyl
      dipeptidyl peptidase (Sm-XPDAP, encoded by pepX), a serine protease known to have
      a nutritional role. Considering the potential of proteases as therapeutic targets
      in pathogens, this study was primarily aimed at investigating the role of Sm
      XPDAP in contributing to virulence-related traits. Dipeptidyl peptidase (DPP IV),
      an XPDAP analogous enzyme found in mammalian tissues,is a well known therapeutic
      target in Type II diabetes. Based on the hypothesis that gliptins, commonly used
      as anti-human-DPP IV drugs, may affect bacterial growth upon inhibition of Sm
      XPDAP, we have determined their ex vivo antimicrobial and anti-biofilm activity
      towards S. mutans. All three DPP IV drugs tested reduced biofilm formation as
      determined by crystal violet staining. To link the observed biofilm inhibition to
      the human-DPP IV analogue present in S. mutans UA159, a pepX isogenic mutant was
      generated. In addition to reduced biofilm formation, CLSM studies of the biofilm
      formed by the pepX isogenic mutant showed these were comparable to those formed
      in the presence of saxagliptin, suggesting a probable role of this enzyme in
      biofilm formation by S. mutans UA159. The effects of both pepX deletion and DPP
      IV drugs on the proteome were studied using LC-MS/MS. Overall, this study
      highlights the potential of Sm-XPDAP as a novel anti-biofilm target and suggests
      a template molecule to synthesize lead compounds effective against this enzyme.

PMID- 29580625
TI  - Letter to the Editor: Public Health Nursing.

PMID- 29580626
TI  - Reprint of: A chemical screen identifies trifluoperazine as an inhibitor of
      glioblastoma growth.
AB  - Glioblastoma (GBM) is regarded as the most common malignant brain tumor but
      treatment options are limited. Thus, there is an unmet clinical need for
      compounds and corresponding targets that could inhibit GBM growth. We screened a
      library of 80 dopaminergic ligands with the aim of identifying compounds capable
      of inhibiting GBM cell line proliferation and survival. Out of 45 active
      compounds, 8 were further validated. We found that the dopamine receptor D2
      antagonist trifluoperazine 2HCl inhibits growth and proliferation of GBM cells in
      a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line
      dependent and correlates with variations in dopamine receptor expression profile.
      We conclude that components of the dopamine receptor signaling pathways are
      potential targets for pharmacological interventions of GBM growth.

PMID- 29580628
TI  - Prognostic Usefulness of Tricuspid Annular Diameter for Cardiovascular Events in
      Patients With Tricuspid Regurgitation of Moderate to Severe Degree.
AB  - Functional tricuspid regurgitation (TR) is frequently encountered. Current
      guidelines recommend the surgical correction of severe TR only at the time of
      left valve surgery despite emphasizing the enlarged tricuspid annulus (TA)
      dimension. We attempted to evaluate the relation between TA dimension and
      clinical outcomes of moderate or severe TR. A total of 213 patients (mean age 68
      years, women 68%) with moderate or severe TR secondary to left-sided valve
      surgery, nonvalvular disease, or isolated primary TR were retrospectively
      identified and classified into tertiles of TA dimension. Cardiovascular (CV)
      outcomes were defined as a composite of hospitalization for worsening heart
      failure (HF), stroke, and CV death over a median follow-up of 3.4 years. Upper
      and lower tertiles of TA dimension had high frequencies of left-sided valve
      surgery and isolated primary TR, respectively. TA dimension was correlated with
      TR severity assigned as color Doppler grade and systolic tissue Doppler imaging
      of the tricuspid valve (TDI s'). During follow-up, there were 87 (41%)
      occurrences of primary outcomes: 65 HFs (31%), 13 CV deaths (6%), and 9 strokes
      (4%). There was a high frequency of adverse outcomes in the upper tertile. TA
      dimension and TDI s' were independently related to outcomes. An enlarged TA
      dimension was associated with outcomes irrespective of subgroups according to
      type or severity of TR and TDI s' (p = 0.21, p = 0.77, p = 0.15 for interaction).
      A cut-off value of 4.0 cm for TA dimension was best for CV event occurrence. When
      assessing clinical CV outcomes, TA dimension should be considered, even in
      moderate TR.

PMID- 29580629
TI  - Rates of Echocardiography, Coronary Angiography, and Coronary Intervention
      Associated With Troponin Testing in Hospitalized Patients.
AB  - Diagnosis of acute myocardial infarction (AMI) often depends on detection of
      cardiac troponin elevation >99th percentile. However, troponin elevation is
      commonly found in patients without AMI. We have previously reported an
      association between troponin elevation and rates of electrocardiogram (ECG),
      echocardiography (ECHO), and coronary angiography (CAG) in patients with a
      primary diagnosis of sepsis. We hypothesized that elevated troponin might be
      associated with greater use of ECHO and CAG in primary diagnoses other than
      sepsis and that this correlation might also include percutaneous coronary
      intervention (PCI). We reviewed all inpatient admissions to nine hospitals in
      Texas in 2016 collecting primary International Statistical Classification of
      Diseases and Related Health Problems (International Classification of Diseases
      10) diagnoses, troponin test data, and the presence of ECHO, CAG, or PCI during
      hospitalization. We identified 56,895 unique inpatient admissions, of which
      14,326 (25.2%) were associated with troponin testing. Of patients tested, 26.1%
      had one or more troponin I values >=0.1 ng/ml (99th percentile). Primary ICD-10
      diagnoses were grouped into (1) AMI, (2) primary diagnosis other than AMI (non
      AMI), (3) congestive heart failure (CHF), (4) sepsis, and (5) Other excluding
      AMI, CHF, or sepsis. Troponin testing was itself associated with greater
      utilization of ECHO, CAG, and PCI in all groups except CHF. Troponin I values
      >=0.1 ng/ml were associated with increased rates of ECHO, CAG, and PCI across all
      groups.

PMID- 29580627
TI  - Alcohol Consumption and Risk of Coronary Artery Disease (from the Million Veteran
      Program).
AB  - Moderate alcohol consumption has been associated with a lower risk of coronary
      artery disease (CAD) in the general population but has not been well studied in
      US veterans. We obtained self-reported alcohol consumption from Million Veteran
      Program participants. Using electronic health records, CAD events were defined as
      1 inpatient or 2 outpatient diagnosis codes for CAD, or 1 code for a coronary
      procedure. We excluded participants with prevalent CAD (n = 69,995) or incomplete
      alcohol information (n = 8,449). We used a Cox proportional hazards model to
      estimate hazard ratios and 95% confidence intervals for CAD, adjusting for age,
      gender, body mass index, race, smoking, education, and exercise. Among 156,728
      participants, the mean age was 65.3 years (standard deviation = 12.1) and 91%
      were men. There were 6,153 CAD events during a mean follow-up of 2.9 years.
      Adjusted hazard ratios (95% confidence intervals) for CAD were 1.00 (reference),
      1.02 (0.92 to 1.13), 0.83 (0.74 to 0.93), 0.77 (0.67 to 0.87), 0.71 (0.62 to
      0.81), 0.62 (0.51 to 0.76), 0.58 (0.46 to 0.74), and 0.95 (0.85 to 1.06) for
      categories of never drinker; former drinker; current drinkers of <=0.5 drink/day,
      >0.5 to 1 drink/day, >1 to 2 drinks/day, >2 to 3 drinks/day, and >3 to 4
      drinks/day; and heavy drinkers (>4 drinks/day) or alcohol use disorder,
      respectively. For a fixed amount of ethanol, intake at >=3 days/week was
      associated with lower CAD risk compared with <=1 day/week. Beverage preference
      (beer, wine, or liquor) did not influence the alcohol-CAD relation. Our data show
      a lower risk of CAD with light-to-moderate alcohol consumption among US veterans,
      and drinking frequency may provide a further reduction in risk.

PMID- 29580630
TI  - Feasibility of Performing Radiofrequency Catheter Ablation and Endomyocardial
      Biopsy in the Same Setting.
AB  - In patients with unexplained cardiomyopathy, electroanatomical mapping can
      identify abnormal tissue to target during electrophysiology-guided endomyocardial
      biopsy (EP-guided EMB). The objective of this study is to determine whether
      catheter ablation performed in the same setting as EP-guided EMB increases
      procedural risk. Sixty-seven patients (mean age 54.4 +/- 13.8, 57% male)
      undergoing EP-guided EMB were included. Radiofrequency catheter ablation was
      performed in 17 patients (25%) for ventricular arrhythmias and in 2 (3%) for
      typical atrial flutter. Femoral arterial access was obtained in 90% ablation
      patients and 40% biopsy-only patients; vascular access complications were more
      common in the ablation group than in the EMB-only group (p = 0.02). There were no
      significant differences in rate of tricuspid regurgitation, thromboembolism, or
      pericardial effusion, whether procedural anticoagulation was used. In conclusion,
      catheter ablation and procedural anticoagulation can be combined with EP-guided
      EMB with an increased risk of vascular access complications, but no significant
      increase in intracardiac complications.

PMID- 29580631
TI  - Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients
      With a Patent Infarct Related Coronary Artery After Percutaneous Coronary
      Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy
      [PRomPT] Trial).
AB  - Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong
      predictor of heart failure and mortality. The predictors of long-term remodeling
      after MI have been incompletely studied. We therefore examined the correlates of
      LV remodeling in patients with large ST-segment elevation myocardial infarction
      and a patent infarct artery after percutaneous 2coronary intervention (PCI) from
      the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial.
      Peri-infarct pacing had a neutral effect on long-term remodeling in patients with
      large first MI. The present analysis includes 109 patients in whom an open artery
      was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline
      and 18 months was assessed by transthoracic echocardiography. Multivariable
      models were fit to identify the independent predictors of LVEDV at baseline and
      18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI
      location (p = 0.03) were independently associated with baseline LVEDV. The
      following variables were independent predictors of increased LVEDV at 18 months:
      younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p =
      0.03), shorter time from MI to baseline transthoracic echocardiography (p =
      0.04), baseline LVEDV (p < 0.0001), and lack of statin use (p = 0.03). In
      conclusion, patients with large MI and an open infarct artery after PCI, anterior
      MI location, and male sex were associated with greater baseline LVEDV, but MI
      location was not associated with 18-month LVEDV. In contrast, younger age, peak
      creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were
      associated with long-term LV remodeling.

PMID- 29580632
TI  - Relation of Blood Pressure to Severity of Pericardial Effusion.
AB  - Subacute tamponade is a challenging diagnosis requiring careful consideration of
      both clinical and imaging data. We aimed at exploring the association of initial
      blood pressure with markers of pericardial effusion severity in patients with
      moderate and large pericardial effusion. We conducted a retrospective, single
      center study in 102 well-phenotyped patients with moderate and large pericardial
      effusion. The presenting systolic and diastolic blood pressure recordings were
      divided into tertiles to examine the association between the blood pressure and
      the different established markers of pericardial effusion severity. On
      presentation, 42% of patients had systolic blood pressure exceeding 130 mm Hg,
      and only 5% of patients had systolic blood pressure <90 mm Hg. Patients in the
      lowest blood pressure tertiles did not differ significantly from patients in the
      upper tertiles in terms of clinical, etiologic, or echocardiographic
      characteristics. Although patients who underwent pericardial drainage had higher
      presenting heart rates, no significant differences were seen in the blood
      pressure recordings, either systolic or diastolic (mean 125 mm Hg vs 130 mm Hg, p
      = 0.36 and 76 vs 75 mm Hg, p = 0.82, respectively). In conclusion, systolic and
      diastolic blood pressure recordings upon initial presentation do not demonstrate
      a significant association with markers of effusion severity or the need for
      drainage in patients with moderate and large pericardial effusion.

PMID- 29580633
TI  - Relation of Testosterone Levels to Mortality in Men With Heart Failure.
AB  - We aimed to investigate the impact of testosterone on the prognosis of heart
      failure (HF), as well as the underlying cardiac function, cardiac damage, and
      exercise capacity. We analyzed consecutive 618 men with HF (age 65.9 years).
      These patients were divided into quartiles based on their serum levels of total
      testosterone (TT): first (TT > 631 ng/dl, n = 154), second (462 < TT <= 631
      ng/dl, n = 155), third (300 < TT <= 462 ng/dl, n = 156), and fourth (TT <= 300
      ng/dl, n = 153) quartiles. In the Kaplan-Meier analysis (mean 1,281 days), all
      cause mortality progressively increased throughout from the first to the fourth
      groups. In the multivariable Cox proportional hazard analysis, TT was found to be
      an independent predictor of all-cause mortality (hazard ratio 0.929, p = 0.042).
      In addition, we compared the parameters of echocardiography and cardiopulmonary
      exercise testing, as well as levels of B-type natriuretic peptide and cardiac
      troponin I, among the 4 groups. Left ventricular ejection fraction and B-type
      natriuretic peptide did not differ among the groups. In contrast, the fourth
      quartile, compared with the first, second, and third groups, had higher levels of
      troponin I and lower peak VO2 (p <0.05, respectively). Decreased serum
      testosterone is associated with myocardial damage, lower exercise capacity, and
      higher mortality in men with HF.

PMID- 29580634
TI  - The relationship between posttraumatic and depressive symptoms during virtual
      reality exposure therapy with a cognitive enhancer.
AB  - Two studies suggest that reductions in posttraumatic symptoms (Aderka et al.,
      2013) and cognitions (Zalta et al., 2014) precede reductions in depressive
      symptoms during prolonged exposure (PE) therapy for posttraumatic stress disorder
      (PTSD) in female assault survivors. The present study explored the temporal
      relationship between posttraumatic and depressive symptoms in a randomized trial
      of D-Cycloserine (DCS) versus placebo augmented virtual reality exposure (VRE)
      therapy for chronic World Trade Center-related PTSD following the September 11,
      2001 terrorist attacks. Twenty-five male and female participants were randomly
      assigned to receive either 100 mg DCS (N = 13) or placebo (N = 12) 90 min before
      12 weekly VRE sessions. Participants contributed a total of 280 weekly PTSD
      Checklist (PCL; Weathers et al., 1993) and Beck Depression Inventory-second
      edition (BDI-II; Beck et al., 1996) symptom scores. Two sets of mediation
      analyses for longitudinal mixed models assessed the effects of 1) lagged PCL on
      BDI-II (Model 1), and 2) lagged BDI-II on PCL (Model 2) in the VRE-DCS and VRE
      Placebo treatment groups, respectively. Results revealed reciprocal relations
      between posttraumatic and depressive symptoms during VRE treatment, although
      reductions in posttraumatic symptoms led to subsequent reductions in depressive
      symptoms to a greater extent than the converse. These effects were stronger in
      the DCS-enhanced group. Findings suggest that VRE primarily decreases
      posttraumatic symptoms, which in turn leads to decreased depressive symptoms, and
      that DCS may strengthen these effects.

PMID- 29580635
TI  - Prevention and treatment of hyperphosphatemia in chronic kidney disease.
AB  - Hyperphosphatemia has consistently been shown to be associated with dismal
      outcome in a wide variety of populations, particularly in chronic kidney disease
      (CKD). Compelling evidence from basic and animal studies elucidated a range of
      mechanisms by which phosphate may exert its pathological effects and motivated
      interventions to treat hyperphosphatemia. These interventions consisted of
      dietary modifications and phosphate binders. However, the beneficial effects of
      these treatment methods on hard clinical outcomes have not been convincingly
      demonstrated in prospective clinical trials. In addition, exposure to high
      amounts of dietary phosphate may exert untoward actions even in the absence of
      overt hyperphosphatemia. Based on this concept, it has been proposed that the
      same interventions used in CKD patients with normal phosphate concentrations be
      used in the presence of hyperphosphatemia to prevent rise of phosphate
      concentration and as an early intervention for cardiovascular risk. This review
      describes conceptual models of phosphate toxicity, summarizes the evidence base
      for treatment and prevention of hyperphosphatemia, and identifies important
      knowledge gaps in the field.

PMID- 29580636
TI  - Pyrophosphate deficiency in vascular calcification.
AB  - Pathologic cardiovascular calcification is associated with a number of conditions
      and is a common complication of chronic kidney disease. Because ambient calcium
      and phosphate levels together with properties of the vascular matrix favor
      calcification even under normal conditions, endogenous inhibitors such as
      pyrophosphate play a key role in prevention. Genetic diseases and animal models
      have elucidated the metabolism of extracellular pyrophosphate and demonstrated
      the importance of pyrophosphate deficiency in vascular calcification. Therapies
      based on pyrophosphate metabolism have been effective in animal models, including
      renal failure, and hold promise as future therapies to prevent vascular
      calcification.

PMID- 29580638
TI  - The effectiveness of influenza vaccination among nursery school children in China
      during the 2016/17 influenza season.
AB  - BACKGROUND: The effectiveness of influenza vaccine among nursery school children
      has not been systematically studied. We conducted a cohort study of children from
      13 nursery schools in Suzhou, China, to estimate the effectiveness of influenza
      vaccine against laboratory-confirmed influenza during 2016-17. METHODS: Children
      aged 36-72 months were chosen from 13 nursery schools from 3 District in Suzhou.
      The surveillance started 2 weeks after vaccination during October 2016-February
      2017. Class teachers reported the names of students with ILI (influenza-like
      illness) to study clinicians on each school day. Further, local physicians
      collected the student's nasopharyngeal swab or throat swab, either at a study
      clinic or at the child's home. The swabs were sent to the National Influenza
      Network Laboratory in Suzhou Center for Disease Control and Prevention for
      influenza testing by RT-PCR. RESULT: A total of 4614 children were enrolled, of
      which 15 children (vaccinated: 2; unvaccinated: 13) were lost to follow-up. Of
      the remaining 4599 children, 558 swabs were collected. Among these swabs, 70
      samples tested positive for influenza virus; 17 in the vaccinated group (B
      Victoria: 2; H3N2: 15) and 53 in the unvaccinated group (B Victoria: 14;
      A(H1N1)pdm09: 1; H3N2: 38). The overall influenza vaccine effectiveness (VE)
      during the influenza season of 2016-2017 was 20.6%. The incidence of developing
      ILI symptoms and healthcare seeking behavior through clinical visits was
      significantly lower in vaccinated children than in the unvaccinated group.
      CONCLUSION: Influenza vaccine protection in vaccinated and unvaccinated children
      showed no statistical difference and the VE percentage varied for different virus
      subtypes. However, the incidence rate of developing ILI and healthcare seeking
      behavior was significant lower in the vaccinated group than in the unvaccinated
      children. Larger studies are required to estimate the VE according to the
      influenza type, subtype, and lineage during influenza seasons in China in the
      future.

PMID- 29580637
TI  - Detection of renin lineage cell transdifferentiation to podocytes in the kidney
      glomerulus with dual lineage tracing.
AB  - Understanding of cellular transdifferentiation is limited by the technical
      inability to track multiple lineages in vivo. To overcome this we developed a new
      tool to simultaneously fate map two distinct cell types in the kidney, and
      genetically test whether cells of renin lineage (CoRL) can transdifferentiate to
      a podocyte fate. Ren1cCreER/tdTomato/Nphs1-FLPo/FRT-EGFP mice (CoRL-PODO mice)
      were generated by crossing Ren1c-CreER/tdTomato CoRL reporter mice with Nphs1
      FLPo/FRT-EGFP podocyte reporter mice. Following tamoxifen administration in these
      animals, CoRL were labeled with red fluorescence (tdTomato) and co-localized with
      renin. Podocytes were labeled green (enhanced green fluorescent protein) and co
      localized with nephrin. Following podocyte loss by nephrotoxic antibody and
      subsequent enalapril-enhanced partial replacement, tdTomato-EGFP-labeled CoRL
      were detected as yellow-colored cells in a subset of glomerular tufts, without
      the use of antibodies. Co-localization with podocin indicated that these cells
      are podocytes, derived from CoRL origin. Thus, our novel study shows that two
      distinct cell types can be simultaneously labeled in the mouse kidney and provide
      strong genetic evidence in vivo that lost podocytes can be replaced in part by
      CoRL.

PMID- 29580639
TI  - Official batch control of influenza vaccines: Is it still useful?
AB  - INTRODUCTION: The governmental quality control of human vaccines is a long
      established tradition in many European countries. In Germany, vaccines have been
      controlled by a governmental agency since 1935. In the beginning, vaccine
      production and control was a purely national activity. However, that changed
      fundamentally in 1994 when the so-called Official Control Authority Batch Release
      Network (OCABR) was implemented shortly after the establishment of the European
      Union. Today, Official Medicinal Control Laboratories (OMCLs) are part of the
      European OCABR Network. In many European countries, OMCLs experimentally test
      every batch of human vaccines before they enter the market. We wanted to gain
      insights into the benefits of batch release by the Network and address the
      question whether batch release is still useful. This question was investigated in
      the context of influenza vaccines. METHODS: Notifications on influenza vaccines
      circulated from 2006 to 2016 within the OCABR network were compiled and organized
      into 32 cases. The impact of these findings was evaluated, and the communication
      pathways between companies and respective European control laboratories were
      examined. RESULTS: Approximately 5850 batches were tested by the OMCL network
      between 2006 and 2016. Among these, notifications belonging to 32 cases were
      observed. The predominant proportion of the circulated notifications related to
      manufacturing issues. In most cases, the manufacturer itself had withdrawn the
      batches before they entered the market. However, in three cases, batches of
      insufficient quality were detected by the respective European Control Laboratory
      leading to withdrawal of 13 batches. CONCLUSION: 13 batches which did not meet
      the specifications of influenza vaccine were detected by the OMCL network between
      2006 and 2016 which would not have been identified by the manufacturer. This
      demonstrates the impact of governmental batch release. Together with the
      intrinsic values of the OCABR system and keeping in mind that vaccines are given
      to healthy often young individuals, governmental batch release of influenza
      vaccines is still justified.

PMID- 29580640
TI  - A randomized, open label trial to evaluate and compare the immunogenicity and
      safety of a novel liquid hexavalent DTwP-Hib/Hep B-IPV (EasySixTM) to licensed
      combination vaccines in healthy infants.
AB  - : Immunogenicity and safety of a newly developed liquid DTwP-Hib/HepB-IPV
      hexavalent vaccine (EasySixTM) was evaluated and compared with administration of
      commercially licensed Pentavac SD(r) (DTwP-HepB/Hib) and Imovax Polio(r) vaccine
      in an open-label, randomized multi-centric trial. 284 participants, aged 6
      10weeks, randomized in a 1:1 allocation, received three doses of test or
      comparator vaccines, administered 4weeks apart. Immunogenicity of the vaccines
      was determined by measuring the baseline and post-vaccination antibody responses
      and comparing the proportions of subjects achieving seroprotection against the
      vaccine antigens; safety was evaluated in terms of solicited (local and systemic)
      and unsolicited incidences in the follow up phase. Post-vaccination,
      seroprotection was achieved against all six vaccine antigens in both vaccine
      groups. The seroresponse rate as well as geometric mean titers of antibody for
      all vaccine components were comparable between EasySixTM and Pentavac SD(r)
      Imovax Polio(r) group. Both vaccines had similar reactogenicity profiles and were
      well tolerated; all adverse events resolved completely without any sequelae. Only
      one serious adverse event was reported that completely resolved; it was regarded
      unconnected to the vaccine administered. This study demonstrated that
      immunogenicity and safety profiles of EasySixTM vaccine, manufactured by Panacea
      Biotec Ltd, are non-inferior to the commercially available vaccines. CLINICAL
      TRIAL REGISTRATION: CTRI/2015/02/005578.

PMID- 29580641
TI  - Status of HPV vaccine introduction and barriers to country uptake.
AB  - During the last 12 years, over 80 countries have introduced national HPV
      vaccination programs. The majority of these countries are high or upper-middle
      income countries. The barriers to HPV vaccine introduction remain greatest in
      those countries with the highest burden of cervical cancer and the most need for
      vaccination. Innovation and global leadership is required to increase and sustain
      introductions in low income and lower-middle income countries.

PMID- 29580643
TI  - Japanese encephalitis virus/yellow fever virus chimera is safe and confers full
      protection against yellow fever virus in intracerebrally challenged mice.
AB  - Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow
      fever virus (YFV), which remains a potential threat to public health. The live
      attenuated YF vaccine (17D strain) is a safe and highly effective measure against
      YF. However, increasing adverse events have been associated with YF vaccinations
      in recent years; thus, safer, alternative vaccines are needed. In this study,
      using the Japanese encephalitis live vaccine strain SA14-14-2 as a backbone, a
      novel chimeric virus was constructed by replacing the pre-membrane (prM) and
      envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a
      reduced growth rate and a much smaller plaque morphology than did either parental
      virus. Furthermore, the chimera was much less neurovirulent than was YF17D and
      protected mice that were challenged with a lethal dose of the YF virus. These
      results suggest that this chimera has potential as a novel attenuated YF vaccine.

PMID- 29580642
TI  - Impact of community-delivered SMS alerts on dog-owner participation during a mass
      rabies vaccination campaign, Haiti 2017.
AB  - Haiti has historically vaccinated between 100,000 and 300,000 dogs annually
      against rabies, however national authorities have not been able to reach and
      maintain the 70% coverage required to eliminate the canine rabies virus variant.
      Haiti conducts massive dog vaccination campaigns on an annual basis and utilizes
      both central point and door-to-door methods. These methods require that dog
      owners are aware of the dates and locations of the campaign. To improve this
      awareness among dog owners, 600,000 text messages were sent to phones in two
      Haitian communes (Gonaives and Saint-Marc) to remind dog owners to attend the
      campaign. Text messages were delivered on the second day and at the mid-point of
      the campaign. A post-campaign household survey was conducted to assess dog
      owner's perception of the text messages and the impact on their participation in
      the vaccination campaign. Overall, 147 of 160 (91.9%) text-receiving dog owners
      indicated the text was helpful, and 162 of 187 (86.6%) responding dog owners said
      they would like to receive text reminders during future rabies vaccination
      campaigns. In areas hosting one-day central point campaigns, dog owners who
      received the text were 2.0 (95% CI 1.1, 3.6) times more likely to have
      participated in the campaign (73.1% attendance among those who received the text
      vs 36.4% among those who did not). In areas incorporating door-to-door
      vaccination over multiple days there was no significant difference in
      participation between dog owners who did and did not receive a text. Text message
      reminders were well-received and significantly improved campaign attendance,
      indicating that short message service (SMS) alerts may be a successful strategy
      in low resource areas with large free roaming dog populations.

PMID- 29580644
TI  - Intracytoplasmic sperm injection use in states with and without insurance
      coverage mandates for infertility treatment, United States, 2000-2015.
AB  - OBJECTIVE: To compare indications and trends in intracytoplasmic sperm injection
      (ICSI) use for in vitro fertilization (IVF) cycles among residents of states with
      and without insurance mandates for IVF coverage. DESIGN: Cross-sectional analysis
      of the National Assisted Reproductive Technology Surveillance System from 2011 to
      2015 for the main outcome and from 2000 to 2015 for trends. SETTING: IVF cycles
      performed in U.S. fertility clinics. PATIENT(S): Fresh IVF cycles.
      INTERVENTION(S): Residency in a state with an insurance mandate for IVF (n = 8
      states) versus no mandate (n = 43 states, including DC). MAIN OUTCOME MEASURE(S):
      ICSI use by insurance coverage mandate status stratified by male-factor
      infertility diagnosis. RESULT(S): During 2000-2015, there were 1,356,377 fresh
      IVF cycles, of which 25.8% (n = 350,344) were performed for residents of states
      with an insurance coverage mandate for IVF. ICSI use increased significantly
      during 2000-2015 in states both with and without a mandate; however, for non-male
      factor infertility cycles, the percentage increase in ICSI use was greater among
      nonmandate states (34.6% in 2000 to 73.9% in 2015) versus mandate states (39.5%
      in 2000 to 63.5% in 2015). For male-factor infertility cycles, this percentage
      increase was ~7.3% regardless of residency in a state with an insurance mandate
      for IVF. From 2011 to 2015, ICSI use was lower in mandate versus nonmandate
      states, both for cycles with (91.5% vs. 94.5%), and without (60.3% vs. 70.9%)
      male-factor infertility. CONCLUSION(S): Mandates for IVF coverage were associated
      with lower ICSI use for non-male-factor infertility cycles.

PMID- 29580645
TI  - Search for new molecular biomarkers to diagnose endometriosis continues.

PMID- 29580646
TI  - Assessment of 30-day mortality and complication rates associated with extended
      deep vein thrombosis prophylaxis following hip fracture surgery.
AB  - BACKGROUND: DVT is a common complication following lower extremity surgery,
      occurring in up to 60% of patients undergoing hip fracture surgery without
      postoperative anticoagulation. The risk of fatal PE continues well-beyond two
      weeks postoperatively, thus extended DVT prophylaxis beyond 14 days may be
      warranted. This investigation sought to examine the association between
      prescription of extended DVT prophylaxis and 30-day postoperative complications
      following hip fracture surgery. METHODS: This study utilized the ACS NSQIP Hip
      Fracture Procedure Targeted dataset, a newly available set of patient variables
      for 2016. The outcome measures were death, occurrence of any postoperative
      complication, complication subtype, readmission or reoperation within 30-days
      postoperatively, and length of stay. The primary independent variable was medical
      DVT prophylaxis continued 28-days postoperatively ("extended DVT prophylaxis").
      The control group contains both patients receiving no prophylaxis and those
      receiving short-duration prophylaxis. Multivariate stepwise logistic regression
      was employed to control for potential demographic, comorbidity, and
      procedural/medical confounding factors. RESULTS: In total, 7533 surgically
      treated hip fracture patients treated in 2016 were analyzed. Overall, 57.8% of
      patients (n = 4354) were prescribed extended DVT prophylaxis. On bivariate
      analysis, prescription of extended DVT prophylaxis was associated with
      significantly lower incidence of death (7.7% without vs. 2.7% with, p < 0.0001)
      and stroke/CVA (1.4% vs. 0.6%, p = 0.0016). In multivariate analysis,
      prescription of extended DVT prophylaxis was significantly associated with lower
      odds of death (OR 0.33, p < 0.0001), stroke/CVA (OR 0.44, p = 0.0010), and acute
      kidney injury (AKI) (OR 0.31, p = 0.0010). CONCLUSIONS: This retrospective cohort
      study of the 2016 ACS NSQIP found that hip fracture surgery patients prescribed
      >=28 days of postoperative DVT prophylaxis exhibited 67% lower odds of death and
      significantly lower rates of AKI and stroke/CVA as compared to those prescribed
      short-duration prophylaxis. Given the retrospective and uncontrolled nature of
      this analysis, these results should be interpreted with caution, and additional
      prospective randomized controlled trials examining the association between
      extended DVT prophylaxis and postoperative outcomes are warranted. If these
      observations accurately reflect real-world experience, these data suggest that
      >=28 days of DVT prophylaxis following hip fracture surgery should be strongly
      considered for patients without explicit contraindications.

PMID- 29580647
TI  - Evaluation of the DiversiLab(r) automated repetitive sequence-based PCR system
      for the characterization of Candida albicans and Candida glabrata isolates.
AB  - The objective of our study was to assess the DiversiLab(r) automated repetitive
      sequence-based PCR (rep-PCR) system for typing C. albicans and C. glabrata
      isolates and to compare it with two proven and routinely used typing methods. A
      total of 39 isolates from 11 patients with candidaemia or tissue candidiasis (two
      to six isolates per patient) were analyzed with three typing methods:
      DiversiLab(r) rep-PCR, multilocus sequence typing and multilocus microsatellite
      typing. DiversiLab(r) rep-PCR results were consistent with those obtained using
      the two other typing methods for C. albicans, but not for C. glabrata. Thanks to
      its simplicity of use, rapidity, standardization and reproducibility, the
      DiversiLab(r) rep-PCR system is an interesting tool to investigate C. albicans
      infections.

PMID- 29580648
TI  - Ageing with a learning disability: Care and support in the context of austerity.
AB  - Recent work in geography has begun to look at the opportunities for care from
      siblings, friends and neighbours alongside parents and spouses. This paper
      examines the daily relationships that middle to older age adults with a learning
      disability have with remaining kin members, friends, and neighbours, within the
      context of declining formal day services. Adults with learning disabilities are
      more likely to have different life course experiences and be living on low
      incomes and in poor housing than the rest of the population as they have had less
      opportunity to work and save money through their lives. We draw on two
      qualitative studies with adults with learning disabilities. Findings suggest that
      friend and kin networks are anything but certain, as opportunities to meet and
      socialise shrink, and connections with siblings do not necessarily lend
      themselves to support. The findings raise the possibility of a space of
      attenuated care to convey the increasingly limited fronts from which support can
      be derived.

PMID- 29580649
TI  - Recommendations for newborn screening for galactokinase deficiency: A systematic
      review and evaluation of Dutch newborn screening data.
AB  - INTRODUCTION: Galactokinase (GALK) deficiency causes cataract leading to severe
      developmental consequences unless treated early. Because of the easy prevention
      and rapid reversibility of cataract with treatment, the Dutch Health Council
      advised to include GALK deficiency in the Dutch newborn screening program. The
      aim of this study is to establish the optimal screening method and cut-off value
      (COV) for GALK deficiency screening by performing a systematic review of the
      literature of screening strategies and total galactose (TGAL) values and by
      evaluating TGAL values in the first week of life in a cohort of screened newborns
      in the Netherlands. METHODS: Systematic literature search strategies in OVID
      MEDLINE and OVID EMBASE were developed and study selection, data collection and
      analyses were performed by two independent investigators. A range of TGAL values
      measured by the Quantase Neonatal Total Galactose screening assay in a cohort of
      Dutch newborns in 2007 was evaluated. RESULTS: Eight publications were included
      in the systematic review. All four studies describing screening strategies used
      TGAL as the primary screening marker combined with galactose-1-phosphate
      uridyltransferase (GALT) measurement that is used for classical galactosemia
      screening. TGAL COVs of 2200 MUmol/L, 1665 MUmol/L and 1110 MUmol/L blood
      resulted in positive predictive values (PPV) of 100%, 82% and 10% respectively.
      TGAL values measured in the newborn period were reported for 39 GALK deficiency
      patients with individual values ranging from 3963 to 8159 MUmol/L blood and 2
      group values with mean 8892 MUmol/L blood (SD +/- 5243) and 4856 MUmol/L blood
      (SD +/- 461). Dutch newborn screening data of 72,786 newborns from 2007 provided
      a median TGAL value of 110 MUmol/L blood with a range of 30-2431 MUmol/L blood.
      CONCLUSION: Based on TGAL values measured in GALK deficiency patients reported in
      the literature and TGAL measurements in the Dutch cohort by newborn screening we
      suggest to perform the GALK screening with TGAL as a primary marker with a COV of
      2500 MUmol/L blood, combined with GALT enzyme activity measurement as used in the
      classical galactosemia screening, to ensure detection of GALK deficiency patients
      and minimize false positive referrals.

PMID- 29580650
TI  - Significance of PITX2 Promoter Methylation in Colorectal Carcinoma Prognosis.
AB  - BACKGROUND: New treatment modalities and a growing understanding of the complex
      genetic tumor landscape have improved the outcome of colorectal cancer (CRC)
      patients. Nonetheless, more individualized treatment regimens, taking individual
      tumor characteristics into account, have been recently postulated and prognostic
      biomarkers are needed. We therefore evaluated the prognostic potential of paired
      like homeodomain transcription factor 2 (PITX2) promoter methylation in CRC
      patients. MATERIALS AND METHODS: Data of 2 independent cohorts were investigated.
      Tissue specimens of cohort A (n = 179) were analyzed for their methylation in the
      PITX2 promoter region using quantitative methylation-specific polymerase chain
      reaction and compared with publicly available data (PITX2 promoter methylation
      and PITX2 mRNA expression levels) from "The Cancer Genome Atlas Research Network"
      (cohort B, n = 443). Data were correlated with clinicopathological parameters and
      outcome. RESULTS: Tumor samples of both cohorts showed a decreased PITX2 promoter
      methylation level (both P < .001) compared with nonmalignant tissue.
      Additionally, PITX2 promoter hypomethylation was prognostic in univariate and
      multivariate analysis (hazard ratio [HR], 1.97 [95% confidence interval (CI),
      1.12-3.47], P = .018 and HR, 1.89 [95% CI, 1.09-3.29], P = .023), and Kaplan
      Meier analysis (median overall survival, 53.2 vs. 70.4 months, P = .004).
      Subanalysis of high-risk vs. low-risk stage II CRC patients also showed a PITX2
      hypomethylation of the promoter region in the high-risk group (P = .006).
      CONCLUSION: Our results suggest a prognostic role of PITX2 promoter methylation
      in CRC as biomarker for risk stratification in stage II CRC patients although the
      results need to be independently validated.

PMID- 29580651
TI  - [Ocular tuberculosis : A case series].
AB  - OBJECTIVES: Ocular tuberculosis is a rare form of extra pulmonary tuberculosis.
      It represents 1-2% of all clinical forms. The aim of this work was to focus on
      diagnostic and therapeutic characteristics of ocular tuberculosis. METHODS: We
      report a case series of 14 patients with ocular tuberculosis seen in an
      infectious diseases department between 2006 and 2015. The diagnosis was retained
      on clinical data and a positive tuberculin skin test or interferon-gamma release
      assay. RESULTS: The patient's mean age was 40.7+/-9years. The most common
      clinical presentation was uveitis (11 patients and 16 eyes). An extra ocular
      involvement was associated in three patients. The mean duration of antitubercular
      therapy was 10+/-2.5 months. Corticosteroid therapy was associated in 11 cases.
      The outcome was favorable in all cases. Two patients had maintained visual
      sequelae. CONCLUSION: Ocular tuberculosis is a rare disease but still remains a
      diagnostic problem. It should be considered in case of any chronic ocular
      symptoms, especially in endemic countries. Early management can improve the
      visual prognosis.

PMID- 29580652
TI  - Gambling behavior in Parkinson's Disease: Impulsivity, reward mechanism and
      cortical brain oscillations.
AB  - Psychopathological components, such as reward sensitivity and impulsivity, and
      dopaminergic treatment are crucial characteristics related to the development of
      Pathological Gambling (PG) in Parkinson's Disease (PD). The aim of the present
      study is to investigate the differences in decision-making in PD patients with or
      without PG considering both neurophysiological and behavioral aspects. The IOWA
      Gambling Task (IGT) and electroencephalographic (EEG) activity were considered to
      elucidate the decision and post-feedback processes in PG. The sample included
      fifty-two PD patients, divided in three groups: 17 PD patients with active
      gambling behavior (PD Gamblers, PDG); 15 PD patients who remitted from PG (PD Non
      Gamblers, PDNG); and a Control Group (CG) composed by 20 patients with PD only.
      EEG and IGT performance were recorded during decision and post-feedback phase.
      Results showed worse performance and an increase of the low frequency bands in
      the frontal area for the PDG group compared to the other two groups. In addition,
      higher BAS (Behavioral Activation System) and BIS-11 (Barratt Impulsiveness
      Scale) personality components were correlated to groups' behavioral response.
      These results show an anomalous behavioral (IGT) and cortical response of PDG
      patients related to their inability to use adequate control mechanisms during a
      decision-making task where reward mechanisms (BAS) and impulsivity (BIS-11) are
      relevant.

PMID- 29580653
TI  - Teaching model based on competencies: Brief review and practical application in
      anesthesia for thoracic surgery.

PMID- 29580654
TI  - Reducing the cost of left ventricular assist devices: Why it matters and can it
      be done?

PMID- 29580655
TI  - Protection of the rat brain from hypothermic circulatory arrest injury by a
      chipmunk protein.
AB  - OBJECTIVES: The study objectives were to test the hypothesis that special protein
      exists in hibernating chipmunk albumin and whether this protein has a
      neuroprotective effect in Sprague-Dawley rats during deep hypothermia circulatory
      arrest. METHODS: Forty chipmunks were allocated into a hibernation group and an
      active group (20 chipmunks in each group). Special protein was detected and
      isolated from hibernating chipmunk albumin. Forty Sprague-Dawley rats were
      randomly divided into a sham group, deep hypothermia circulatory arrest group,
      special protein group, and naloxone group (10 rats in each group). Special
      protein that was detected and collected from hibernating chipmunks were injected
      in rats in the special protein group for 3 consecutive days before operation, and
      naloxone was given at the same time in the naloxone group. Rats were subjected to
      cardiopulmonary bypass and 60-minute deep hypothermia circulatory arrest. Tumor
      necrosis factor-alpha and interleukin-6 levels were detected. Animals received
      neurologic testing. Relative protein expression, malondialdehyde, and superoxide
      dismutase of hippocampus were detected. The brain was fixed for histopathologic
      assessment. RESULTS: The rats that received special protein displayed ischemic
      tolerance after deep hypothermia circulatory arrest. The neuroprotective effect
      could be reversed by naloxone. The inflammation response was attenuated in the
      special protein group (P < .008, compared with the deep hypothermia circulatory
      arrest and naloxone groups). The mature brain-derived neurotrophic factor and
      SIRT1 levels were higher in the special protein group (P < .01, compared with the
      deep hypothermia circulatory arrest and naloxone groups). Histopathologic
      assessment showed that the injury in the special protein group was attenuated
      (pathological score, P < .05; surviving hippocampal CA1 neurons, P < .01; TUNEL
      positive neurons, P < .01; compared with deep hypothermia circulatory arrest and
      naloxone groups). Intravenous injection of special protein significantly improved
      neurologic recovery. CONCLUSIONS: We found that a specific protein existed in
      hibernating chipmunk albumin and could play an important neuroprotective role in
      rats.

PMID- 29580656
TI  - Should prostacyclin be wrapped inside a fatty flap?

PMID- 29580657
TI  - Let's just do what we must.

PMID- 29580658
TI  - Transcutaneous Auricular Vagus Nerve Stimulation with Concurrent Upper Limb
      Repetitive Task Practice for Poststroke Motor Recovery: A Pilot Study.
AB  - BACKGROUND: Invasive vagus nerve stimulation (VNS) has the potential to enhance
      the effects of physiotherapy for upper limb motor recovery after stroke.
      Noninvasive, transcutaneous auricular branch VNS (taVNS) may have similar
      benefits, but this has not been evaluated in stroke recovery. We sought to
      determine the feasibility of taVNS delivered alongside upper limb repetitive task
      specific practice after stroke and its effects on a range of outcome measures
      evaluating limb function. MATERIALS AND METHODS: Thirteen participants at more
      than 3 months postischemic stroke with residual upper limb dysfunction were
      recruited from the community of Sheffield, United Kingdom (October-December
      2016). Participants underwent 18 * 1-hour sessions over 6 weeks in which they
      made 30-50 repetitions of 8-10 arm movements concurrently with taVNS (NEMOS;
      Cerbomed, Erlangen, Germany, 25 Hz, .1-millisecond pulse width) at maximum
      tolerated intensity (mA). An electrocardiogram and rehabilitation outcome scores
      were obtained at each visit. Qualitative interviews determined the acceptability
      of taVNS to participants. RESULTS: Median time after stroke was 1.16 years, and
      baseline median/interquartile range upper limb Fugl-Meyer (UFM) score was 63
      (54.5-99.5). Participants attended 92% of the planned treatment sessions. Three
      participants reported side effects, mainly fatigue, but all performed mean of
      more than 300 arm repetitions per session with no serious adverse events. There
      was a significant change in the UFM score with a mean increase per participant of
      17.1 points (standard deviation 7.8). CONCLUSION: taVNS is feasible and well
      tolerated alongside upper limb repetitive movements in poststroke rehabilitation.
      The motor improvements observed justify a phase 2 trial in patients with residual
      arm weakness.

PMID- 29580659
TI  - Impact of iron deficiency on long-term clinical outcomes of hospitalized patients
      with heart failure.
AB  - BACKGROUND: Iron deficiency (ID) is commonly observed in chronic heart failure
      (HF) patients and is associated with worse clinical outcomes. While ID is
      frequent finding in hospitalized heart failure (HHF), its impact on long-term
      outcome in HHF patients remains unclear. METHODS: We evaluated iron status at
      discharge in 578 HHF patients. Absolute ID was defined as serum ferritin <100
      MUg/L, and functional ID (FID) was defined as serum ferritin of 100-299 MUg/L
      with transferrin saturation <20%. The primary outcome of interest was the
      composite of all-cause mortality and HF admission at one year. RESULTS: Among the
      study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID.
      At one-year post-discharge, 64 patients had died and 112 had been readmitted with
      HF. Patients with absolute ID had more adverse events than those with FID or no
      ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was
      significantly associated with increased risk of adverse events at one year (HR
      1.50, 95% CI 1.02-2.21, p = 0.040) compared with the remaining patients.
      Sensitivity analysis revealed that its prognostic effect did not differ across
      anemic status, or between HF with reduced and preserved ejection fraction (p for
      interaction = 0.17, 0.68, respectively). CONCLUSION: Absolute ID, but not FID, at
      discharge was associated with increased risk of one-year mortality or HF
      admission in patients with HHF. Further studies are required to evaluate the role
      of repleting iron stores and its impact on clinical outcomes in patients with
      HHF.

PMID- 29580661
TI  - New Treatment Options for Hepatitis C Virus Infection in End-Stage Kidney
      Disease: To Treat or Not to Treat.

PMID- 29580660
TI  - CKD Self-management: Phenotypes and Associations With Clinical Outcomes.
AB  - BACKGROUND: To slow chronic kidney disease (CKD) progression and its
      complications, patients need to engage in self-management behaviors. The
      objective of this study was to classify CKD self-management behaviors into
      phenotypes and assess the association of these phenotypes with clinical outcomes.
      STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adults with mild
      to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.
      3,939 participants in the CRIC Study recruited between 2003 and 2008 served as
      the derivation cohort and 1,560 participants recruited between 2013 and 2015
      served as the validation cohort. PREDICTORS: CKD self-management behavior
      phenotypes. OUTCOMES: CKD progression, atherosclerotic events, heart failure
      events, death from any cause. MEASUREMENTS: Latent class analysis stratified by
      diabetes was used to identify CKD self-management phenotypes based on measures of
      body mass index, diet, physical activity, blood pressure, smoking status, and
      hemoglobin A1c concentration (if diabetic); Cox proportional hazards models.
      RESULTS: 3 identified phenotypes varied according to the extent of implementation
      of recommended CKD self-management behaviors: phenotype I characterized study
      participants with the most recommended behaviors; phenotype II, participants with
      a mixture of recommended and not recommended behaviors; and phenotype III,
      participants with minimal recommended behaviors. In multivariable-adjusted models
      for those with and without diabetes, phenotype III was strongly associated with
      CKD progression (HRs of 1.82 and 1.49), death (HRs of 1.95 and 4.14), and
      atherosclerotic events (HRs of 2.54 and 1.90; each P < 0.05). Phenotype II was
      associated with atherosclerotic events and death among those with and without
      diabetes. LIMITATIONS: No consensus definition of CKD self-management; limited to
      baseline behavior data. CONCLUSIONS: There are potentially 3 CKD self-management
      behavior phenotypes that distinguish risk for clinical outcomes. These phenotypes
      may inform the development of studies and guidelines regarding optimal self
      management.

PMID- 29580663
TI  - Asian Fish Tapeworm: The Most Successful Invasive Parasite in Freshwaters.
AB  - The Asian fish tapeworm (AFT), Schyzocotyle acheilognathi, is a notorious and
      highly successful invasive parasite reported in a wide spectrum of freshwater
      fishes, and new reports of its spread continue to emerge. To date, no thorough
      review of its worldwide distribution and host associations is available. In the
      present work, we collected information from 651 articles up until 2017, from
      which we updated the number of the hosts to 312 fish species and 11 non-fish
      species, which is quite unusual among helminths. The AFT has spread to all but
      one continent (Antarctica). The highest number of records are from North America,
      followed by Asia and Europe. A key feature of its invasive success is its broad
      environmental tolerance.

PMID- 29580664
TI  - Diabetes mellitus as a protective factor of abdominal aortic aneurysm: Possible
      mechanisms.
AB  - Abdominal aortic aneurysm (AAA) shares several risk factors with atherosclerosis.
      Among these, diabetes mellitus (DM) could have a negative effect on the
      formation, growth and expansion of AAA. Several systematic reviews and meta
      analyses reported up to 2016 have shown concordant results regarding the possible
      protective effect on AAA formation. However, the pathophysiological mechanisms of
      this supposed protective effect are still unknown. It appears that both
      hyperglycaemia and hyperinsulinemia, which are closely associated with DM, cause
      an increase in advanced glycation end-products, a decrease in fibrinolysis, and
      alterations in smooth muscle cells, leading to a decreased risk of aneurysm
      growth and expansion. This protective role is mainly mediated by a decrease in
      metalloproteinases, mainly type 2 and 9. In addition, drugs used to treat type 2
      DM, as well as those for hypertension and dyslipidaemia could also play an
      important role in this protective effect. Metformin, thiazolidinediones, DPP4
      inhibitors, statins, and angiotensin-converting enzyme inhibitors have been
      evaluated in this field. In conclusion, studies reported so far seem to confirm
      the protective effect of DM in both the formation and expansion of AAA, although
      future long-term studies are needed to confirm the pathophysiological mechanisms
      involved, as well as the role of concomitant medication.

PMID- 29580662
TI  - Duration of Living Kidney Transplant Donor Evaluations: Findings From 2
      Multicenter Cohort Studies.
AB  - BACKGROUND: A prolonged living kidney donor evaluation may result in worse
      outcomes for transplant recipients. Better knowledge of the duration of this
      process may help inform future donors and identify opportunities for improvement.
      STUDY DESIGN: 1 prospective and 1 retrospective cohort study. SETTING &
      PARTICIPANTS: At 16 Canadian and Australian transplantation centers (prospective
      cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed
      the duration of living kidney donor evaluation and explored donor, recipient, and
      transplantation factors associated with longer evaluation times. Data were
      obtained from 2 sources: donor medical records using chart abstraction and health
      care administrative databases. PREDICTORS: Donor and recipient demographics,
      direct versus paired donation, center-level variables. OUTCOMES: Duration of
      living donor evaluation. RESULTS: The median total duration of transplantation
      evaluation (time from when the candidate started the evaluation until donation)
      was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until
      approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until
      donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the
      first and last consultation among donors who completed a nephrology, surgery, and
      psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months,
      and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2)
      months. After adjustment, the total duration of transplantation evaluation was
      longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7]
      months) and if the recipient was referred later relative to the donor's
      evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed
      referral]). Results depended on whether the recipient was receiving dialysis.
      LIMITATIONS: Living donor candidates who did not donate were not included and
      proxy measures were used for some dates in the donor evaluation process.
      CONCLUSIONS: The duration of kidney transplant donor evaluation is variable and
      can be lengthy. Better understanding of the reasons for a prolonged evaluation
      may inform quality improvement initiatives to reduce unnecessary delays.

PMID- 29580665
TI  - Low T3 syndrome improves risk prediction of in-hospital cardiovascular death in
      patients with acute myocardial infarction.
AB  - BACKGROUND: Low triiodothyronine (T3) syndrome (LT3S) is frequently seen in
      patients with acute myocardial infarction (AMI). We examined the association
      between LT3S and severity of myocardial injury and determined whether LT3S adds
      predictive value over thrombolysis in myocardial infarction (TIMI) risk score for
      in-hospital cardiovascular (CV) death. METHODS: Of 2459 AMI patients, 529 pairs
      of euthyroid and LT3S individuals with similar baseline characteristics were
      identified using 1:1 propensity score matching. LT3S was defined as free T3 (fT3)
      <2.36pg/mL, normal values of thyroid-stimulating hormone and free thyroxin.
      Primary outcome was in-hospital CV death. Receiver operating characteristic
      curves were generated to assess the predictive effects of fT3, TIMI risk score,
      and TIMI-LT3S risk score on in-hospital CV death. RESULTS: LT3S was found in
      23.3% of patients with AMI. The peak values of cardiac troponin I in ng/mL and N
      terminal pro-brain natriuretic peptide in ng/mL were significantly higher in
      LT3S: 6.6 (1.3-19.6) vs. 3.5 (0.8-12.1), p<0.001 and 3625 (1046-12,776) vs. 2158
      (774-6759), p<0.001. Patients with LT3S had significantly higher rate of in
      hospital CV death than those without (4.7% vs. 1.7%, p=0.005). Lower levels of
      fT3 yielded an area under the curve (AUC) of 0.741 for predicting CV death. LT3S,
      when added to the TIMI risk score, significantly increased AUC for in-hospital CV
      death than TIMI risk score alone (0.775 vs. 0.738, p=0.005). CONCLUSIONS: LT3S
      was associated with more severe myocardial injury and increased in-hospital CV
      mortality in patients with AMI. Furthermore, it improved risk prediction of in
      hospital CV death post-AMI when it was added to the TIMI risk score.

PMID- 29580666
TI  - Cultural adaptation and validation of Patient and Observer Scar Assessment Scale
      for Turkish use.
AB  - BACKGROUND: This study aimed to evaluate cross-cultural adaptation, validation,
      and reliability of Patient and Observer Scar Assessment Scale (POSAS) for its
      Turkish use. METHOD: This study included 50 burn patients with hypertrophic scars
      who were aged 18-65 years (mean, 37.5+/-1.4years) and were admitted to Wound and
      Burn Treatment Center from February 2014 to April 2014. With regard to the
      cultural adaptation of POSAS from English to Turkish, the scale was translated by
      two people who worked in different health fields. POSAS was administered to the
      patients with a 1-week interval to evaluate the validity and reliability of the
      scale. Internal consistency of the scale was tested using the Cronbach
      alphamethod. RESULTS: The Cronbach alpha value for the observer measurements was
      found to be 0.93 (excellent), and that for patient measurements was found to be
      0.77 (good). Accordingly, the internal consistency of the scale was established.
      CONCLUSION: The Turkish version of POSAS is a valid, reliable and culturally
      appropriate survey for evaluating hypertrophic scars. We believe that the Turkish
      version of POSAS will be an important clinical/scientific tool in the field of
      burn physiotherapy in Turkey, which will lead to new researches in this field.

PMID- 29580667
TI  - Retinal Degeneration in Choroideremia follows an Exponential Decay Function.

PMID- 29580668
TI  - Medication-related osteonecrosis of the jaw: An update on the memorial sloan
      kettering cancer center experience and the role of premedication dental
      evaluation in prevention.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between type
      of antiresorptive medication and medication-related osteonecrosis of the jaw
      (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the
      prevention of MRONJ. STUDY DESIGN: Our database of patients with MRONJ was
      reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3
      frequent medication types associated with MRONJ. To evaluate the role of PMDE in
      the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic
      medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center
      during a 10-year period were subclassified into 2 groups. Group I comprised
      patients seen for PMDE before the commencement of A/A and group II patients seen
      after prior exposure to antiresorptive and/or antiangiogenic medications.
      Fischer's exact test was used to compare the incidence of MRONJ in both groups.
      RESULTS: Patients on denosumab developed MRONJ earlier compared with zoledronate
      and pamidronate (P = .003). Group I had a significantly reduced incidence of
      MRONJ (0.9%) compared with group II (10.5%) (P < .0001). Dentoalveolar trauma as
      a precipitating factor between groups I and II was not statistically significant.
      CONCLUSIONS: Denosumab was associated with an earlier occurrence of MRONJ
      compared with zoledronate and pamidronate. The role of PMDE may be an effective
      preventive strategy in reducing the incidence of MRONJ.

PMID- 29580669
TI  - The incidence of occult metastasis and the status of elective neck dissection in
      salivary adenoid cystic carcinoma: a single center study.
AB  - OBJECTIVE: Adenoid cystic carcinoma (ACC) is characterized by a high rate of
      local recurrence and late distant metastasis. The status of an elective neck
      dissection (END) is controversial in the literature. STUDY DESIGN: In this study
      we retrospectively analyzed the surgical treatment and follow-up examinations of
      59 patients with ACCs of a salivary gland treated in a single center between 1980
      and 2016. RESULTS: The incidence of occult nodal metastases among all patients
      who underwent END was 20.6%. The overall survival and the disease-free survival
      of patients who underwent END versus patients without END had no significant
      differences. Even in the case of positive lymph nodes metastasis there was no
      significant benefit in survival or local recurrence control. CONCLUSION: The
      incidence of occult neck metastases in patients with ACC was 20.6%. There was no
      significant enhanced survival in the group of patients who underwent an END.

PMID- 29580670
TI  - Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal
      injury in symptomatic late onset Alzheimer's disease.
AB  - INTRODUCTION: Individuals in early stages of Alzheimer's disease are a targeted
      population for secondary prevention trials aimed at preserving normal cognition.
      Understanding within-person biomarker(s) change over time is critical for trial
      enrollment and design. METHODS: Longitudinal cerebrospinal fluid samples from the
      Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of
      neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and
      neuroinflammation (YKL-40) and compared with beta amyloid 42, tau, and phospho
      tau181. General linear mixed models were used to compare within-person rates of
      change in three clinical groups (cognitively normal, mild cognitive impairment,
      and Alzheimer's disease) further defined by beta amyloid status. RESULTS: Levels
      of injury markers were highly positively correlated. Despite elevated baseline
      levels as a function of clinical status and amyloid-positivity, within-person
      decreases in these measures were observed in the early symptomatic, amyloid
      positive Alzheimer's disease group. DISCUSSION: Knowledge of within-person
      biomarker change will impact interpretation of biomarker outcomes in clinical
      trials that are dependent on disease stage.

PMID- 29580671
TI  - Intron-retained transcripts of the spinal muscular atrophy genes, SMN1 and SMN2.
AB  - BACKGROUND: The SMN genes, SMN1 and SMN2, are highly homologous genes which are
      related to the development or clinical severity of spinal muscular atrophy. Some
      alternative splicing patterns of the SMN genes have been well documented. In
      2007, an SMN1 transcript with a full sequence of intron 3 was reported as the
      first intron-retained SMN transcript. METHODS: Intron-retained SMN transcripts in
      various cells and tissues were studied using reverse transcription (RT)-PCR. HeLa
      cells were used for subcellular localization of the transcripts and protein
      expression analysis with Western blotting. RESULTS: Two intron-retained SMN
      transcripts were detected, which contain full sequences of intron 2b or intron 3.
      These transcripts were produced from SMN1 and SMN2, and ubiquitously expressed in
      human cells and tissues. Western blotting analysis showed no proteins derived
      from the intron-retained transcripts. Fractionation analysis showed that these
      intron-retained transcripts were localized mainly in the nucleus. Contrary to our
      expectation, the intron-retained transcript levels decreased during the treatment
      of cycloheximide, an inhibitor of nonsense-mediated decay (NMD), suggesting that
      they were not targets of NMD. CONCLUSION: Intron 2b-retained SMN transcript and
      intron3-retained SMN transcript were ubiquitously expressed in human cells and
      tissues. The intron-retained transcripts were mainly localized in the nucleus and
      decreased through non-NMD pathway.

PMID- 29580672
TI  - Athlete's heart and soldier's heart: Is Morganroth striking back?

PMID- 29580673
TI  - Using a social construction of gender lens to understand gender differences in
      posttraumatic stress disorder.
AB  - A wealth of research has established clear gender differences in exposure to
      potentially traumatic events and in subsequent posttraumatic stress disorder
      (PTSD). One perspective that is missing from most conversations about gender
      differences in PTSD is a systematic discussion of gender role socialization, and
      relatedly, the social construction of gender within our society. The purpose of
      the present review is to provide exposure to these theories as they relate to
      gender differences in PTSD, including differences in trauma exposure, risk for
      the development and maintenance of PTSD symptoms, and PTSD treatment outcome. In
      this review we focus on characteristics and behaviors that arise from a way of
      being in the world that is largely influenced by assigned gender. These include
      gender differences in patterns of trauma exposure, chronic environmental strain,
      behavioral responses to distress, cognitive factors, and the experience and
      expression of emotion. We posit that these different sets of factors reciprocally
      influence each other and combine synergistically to influence observed gender
      differences. The research reviewed here indicates that societal definitions of
      masculinity and femininity have psychological consequences in that they produce
      gender differences in major risk factors relevant to PTSD.

PMID- 29580674
TI  - Are Corticosteroids Superior to Nonsteroidal Anti-inflammatory Drugs in the
      Treatment of Acute Gout?

PMID- 29580676
TI  - Research of falls risk of taking central nervous system drugs in oncology
      inpatients.
AB  - This study aimed to analyze the medication use and related falls risk of central
      nervous system(CNS) drugs in oncology inpatients, explore the association between
      CNS drugs and falls. In this study, we enrolled inpatients, hospitalized in the
      oncology department of the Teaching Hospital of Chengdu University of Traditional
      Chinese Medicine, from March 2013 to October 2015. All inpatients were divided
      into two groups: taking-CNS drugs group (treatment group) and non CNS drugs group
      (control group). The falls risk between two groups were being compared and
      analyzed. Results showed that a total of 768 inpatients were enrolled in this
      study; 401 of them were males and 367 were females; the average age was 47.9+/
      5.8 year-old. Of them, 129 were taking CNS drugs, while 639 were not. In the
      treatment group, the number of fall patients was 39, at an incidence rate of
      30.23%; of the 39 fall patients, 3 suffered fractures, and 1 suffered an
      intracranialhemorrhage; while in the control group, the incidence of falls
      totaled at 45, at an incidence rate of 7.04%; 4 of the patients suffered
      fractures. The difference of incidence rate between two groups had statistical
      significance (P< 0.01). The incidence rate of falls in the treatment group was
      4.29 times that in the control group. By the further analysis of CNS drugs,
      results implied that hypnotics, sedatives, selective serotonin reuptake
      inhibitors (no patient taking tricyclic antidepressants in this study), opioids,
      antiepileptics and antipsychotics had relationship with falls (OR>1). Our finding
      indicates that oncology inpatients have a higher risk of falls resulting from
      taking CNS drugs. Therefore, it is necessary to build up a systemic mechanism of
      nursing safety management on preventing falls of oncology inpatients, to improve
      nursing quality, and reduce the risk of falls.

PMID- 29580675
TI  - Evaluating the Current Status of Rectal Cancer Care in the US: Where We Stand at
      the Start of the Commission on Cancer's National Accreditation Program for Rectal
      Cancer.
AB  - BACKGROUND: In an effort to improve the quality of rectal cancer care in the US,
      the American College of Surgeons Commission on Cancer has developed the National
      Accreditation Program for Rectal Cancer (NAPRC). We aimed to describe the current
      status of rectal cancer care before implementation of the NAPRC. STUDY DESIGN:
      The 2011-2014 National Cancer Database was queried for non-metastatic rectal
      cancer patients who underwent proctectomy. The NAPRC process measures evaluated
      included clinical staging completion, treatment starting fewer than 60 days from
      diagnosis, CEA level drawn before treatment, tumor regression grading, and margin
      assessment. The NAPRC performance measures included negative proximal, distal,
      and circumferential margins, and >=12 lymph nodes harvested during resection.
      RESULTS: There were 39,068 patients identified (mean age 62 years, 61.6% male
      sex). In >85% of patients, clinical staging was completed, treatment was started
      within 60 days, and all tumor margins were assessed. Pretreatment CEA level
      (64.6% complete) was the process measure most often omitted. However, completion
      of all included process measures occurred in only 28.1% of patients. All
      pathologic margins were negative in 79.8% of patients and 73.2% of specimens
      reported >=12 lymph nodes. Overall, 56.3% of patients achieved all performance
      measures. Patients treated at high-volume centers (>30 cases/year) had higher
      odds of meeting all performance measures (odds ratio 1.42; p < 0.001).
      CONCLUSIONS: Overall, very few patients achieved all of the proposed quality
      measures for rectal cancer care. It will be important to re-evaluate these data
      after the implementation of the NAPRC.

PMID- 29580677
TI  - Consomic rats parental strains differ in sensory perception, pain developed
      following nerve injury and in IL-1 beta and IL-6 levels.

PMID- 29580678
TI  - Varicocele with an Abdominal Mass.

PMID- 29580680
TI  - Attention Deficit Hyperactivity Disorder in Childhood: Healthcare Use in a Danish
      Birth Cohort during the First 12 Years of Life.
AB  - OBJECTIVES: To compare the mean number of medical and psychiatric hospital-based
      services in children with and without attention deficit hyperactivity disorder
      (ADHD) and to assess the effect of ADHD on hospital-based service use, including
      child-, parental-, and socioeconomic-related risk factors. STUDY DESIGN: A Danish
      birth cohort was followed through 12 years, and children with ADHD were
      identified using Danish nationwide registries. Poisson regression analyses were
      used to assess the association of ADHD with service use and to adjust for a
      comprehensive set of explanatory variables. RESULTS: Children diagnosed with ADHD
      used more medical and psychiatric hospital-based healthcare than those without
      ADHD. In children with ADHD, intellectual disability and parental psychiatric
      disorder were associated with increased medical and psychiatric service use. Low
      birth weight and low gestational age were associated with increased medical
      service use. Psychiatric comorbidity and having a divorced or single parent were
      associated with increased psychiatric service use. CONCLUSIONS: ADHD
      independently affected medical and psychiatric hospital-based service use even
      when adjusting for a comprehensive set of explanatory variables. However, the
      pattern of medical and psychiatric hospital-based service use is complex and
      cannot exclusively be explained by the child-, parental-, and socioeconomic
      related variables examined in this study.

PMID- 29580679
TI  - Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after
      Home Birth and Early Postnatal Discharge.
AB  - OBJECTIVE: To assess the accuracy of pulse oximetry screening for critical
      congenital heart defects (CCHDs) in a setting with home births and early
      discharge after hospital deliveries, by using an adapted protocol fitting the
      work patterns of community midwives. STUDY DESIGN: Pre- and postductal oxygen
      saturations (SpO2) were measured >=1 hour after birth and on day 2 or 3.
      Screenings were positive if the SpO2 measurement was <90% or if 2 independent
      measures of pre- and postductal SpO2 were <95% and/or the pre-/postductal
      difference was >3%. Positive screenings were referred for pediatric assessment.
      Primary outcomes were sensitivity, specificity, and false-positive rate of pulse
      oximetry screening for CCHD. Secondary outcome was detection of noncardiac
      illnesses. RESULTS: The prenatal detection rate of CCHDs was 73%. After we
      excluded these cases and symptomatic CCHDs presenting immediately after birth, 23
      959 newborns were screened. Pulse oximetry screening sensitivity in the remaining
      cohort was 50.0% (95% CI 23.7-76.3) and specificity was 99.1% (95% CI 99.0-99.2).
      Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61%
      (134) had noncardiac illnesses, including infections (31) and respiratory
      pathology (88). Pulse oximetry screening did not detect left-heart obstructive
      CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity
      to 70.2% (95% CI 56.0-81.4). CONCLUSION: Pulse oximetry screening adapted for
      perinatal care in home births and early postdelivery hospital discharge assisted
      the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal
      detection led to a moderate sensitivity of pulse oximetry screening. The
      screening also detected noncardiac illnesses in 0.6% of all infants, including
      infections and respiratory morbidity, which led to early recognition and referral
      for treatment.

PMID- 29580681
TI  - Head-to-tail macrocyclization of cysteine-free peptides using an o-aminoanilide
      linker.
AB  - A head-to-tail macrocyclization protocol for the preparation of cysteine-free
      cyclic peptides was investigated. The o-aminoanilide linker constructed in the
      peptide sequence by a standard Fmoc-based peptide synthesis procedure was
      subjected to nitrite-mediated activation under acidic conditions toward N-acyl
      benzotriazole as the active ester species. The subsequent cyclization smoothly
      proceeded by neutralization in the presence of additives such as 1
      hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) to afford the
      expected cyclic pentapeptide, a CXCR4 antagonist. The cyclization efficiencies
      were dependent on the precursor open-chain sequence. The application of this step
      wise activation-cyclization protocol to microflow reaction systems is also
      described.

PMID- 29580682
TI  - Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by
      ZFN-Mediated In Vivo Genome Editing.
AB  - Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal
      disorder caused by deficiency of iduronate 2-sulfatase (IDS), leading to
      accumulation of glycosaminoglycans (GAGs) in tissues of affected individuals,
      progressive disease, and shortened lifespan. Currently available enzyme
      replacement therapy (ERT) requires lifelong infusions and does not provide
      neurologic benefit. We utilized a zinc finger nuclease (ZFN)-targeting system to
      mediate genome editing for insertion of the human IDS (hIDS) coding sequence into
      a "safe harbor" site, intron 1 of the albumin locus in hepatocytes of an MPS II
      mouse model. Three dose levels of recombinant AAV2/8 vectors encoding a pair of
      ZFNs and a hIDS cDNA donor were administered systemically in MPS II mice.
      Supraphysiological, vector dose-dependent levels of IDS enzyme were observed in
      the circulation and peripheral organs of ZFN+donor-treated mice. GAG contents
      were markedly reduced in tissues from all ZFN+donor-treated groups. Surprisingly,
      we also demonstrate that ZFN-mediated genome editing prevented the development of
      neurocognitive deficit in young MPS II mice (6-9 weeks old) treated at high
      vector dose levels. We conclude that this ZFN-based platform for expression of
      therapeutic proteins from the albumin locus is a promising approach for treatment
      of MPS II and other lysosomal diseases.

PMID- 29580683
TI  - Mandibular reconstruction with free fibula flaps in the elderly: a retrospective
      evaluation.
AB  - The purpose of this study was to evaluate surgical outcomes in elderly patients
      who had undergone free fibula flap transfer for malignant head and neck tumours.
      A retrospective chart review was performed to identify patients who had undergone
      free fibula flap transfer for mandibular reconstruction after malignant tumour
      resection at Jichi Medical University Hospital between May 2009 and April 2015.
      Enrolled patients were divided into an elderly group (>=80years old) and a
      younger group (<80years old). Seventeen patients met the inclusion criteria and
      were included in the elderly group. Age at surgery ranged from 80 to 92years.
      Thirteen patients (76.5%) experienced postoperative complications. Surgical site
      complications occurred in seven patients. The success rate of free fibula flap
      transfer was 100%. Systemic complications occurred in nine patients, most
      commonly delirium (n=6). No perioperative mortality was encountered. The overall
      1-year survival rate was 94.1% (16/17). No patient reported gait disturbance as a
      donor site complication or any other major complication. The incidence of
      postoperative complications did not differ significantly between the elderly and
      younger groups. Almost no difference in postoperative course was seen between the
      groups. Elderly patients appear to tolerate free fibula flap reconstruction just
      as well as younger patients.

PMID- 29580684
TI  - Comparison of 3 Types of Readmission Rates for Measuring Hospital and Surgeon
      Performance After Primary Total Hip and Knee Arthroplasty.
AB  - BACKGROUND: All-cause 30-day hospital readmission is in widespread use for
      monitoring and incentivizing hospital performance for patients undergoing total
      hip arthroplasty (THA) and total knee arthroplasty (TKA). However, little is
      known on the extent to which all-cause readmission is influenced by hospital or
      surgeon performance and whether alternative measures may be more valid. METHODS:
      This is an observational study using multilevel modeling on English
      administrative data to determine the interhospital and intersurgeon variation for
      3 readmission metrics: all-cause, surgical, and return-to-theater. Power
      calculations estimated the likelihood of identifying whether the readmission rate
      for a surgeon or hospital differed from the national average by a factor of 1.25,
      1.5, 2, or 3 times, for both average and high-volume providers. RESULTS: 259,980
      THAs and 311,033 TKAs were analyzed. Variations by both surgeons and hospitals
      were smaller for the all-cause measure than for the surgical or return-to-theater
      metrics, although statistical power to detect differences was higher. Statistical
      power to detect surgeon-level rates of 1.25 or 1.5 times the average was
      consistently low. However, at the hospital level, the surgical readmission
      measure showed more variation by hospital while maintaining excellent power to
      detect differences in rates between hospitals performing the average number of
      THA or TKA cases per year in England. In practice, more outliers than expected
      from purely random variation were found for all-cause and surgical readmissions,
      especially at hospital level. CONCLUSION: The 30-day surgical readmission rate
      should be considered as an adjunctive measure to 30-day all-cause readmission
      rate when assessing hospital performance.

PMID- 29580685
TI  - Systematic review and pooled analysis of the rate of carpal tunnel syndrome after
      prophylactic carpal tunnel release in patients with a distal radius fracture.
AB  - The aim of this study was to determine the rate of carpal tunnel syndrome (CTS)
      in patients with a volar plated distal radius fracture (DRF), with or without
      prophylactic carpal tunnel release (CTR). The PubMed database was searched for
      studies reporting on CTS in patients with a DRF fixed by a volar plate. Selected
      patients were those who underwent prophylactic CTR versus patients who did not.
      Pooled rates of CTS were calculated using inverse - variance weighting assuming a
      random effects model. Tests for heterogeneity were applied. In this study, 172
      patients in the CTR group and 1839 patients in the non-CTR group were included.
      The pooled rate for CTS in the CTR group was 28.1% (95% CI: 11.8% to 48.2%) while
      it was 4.4% (95% CI: 3.1% to 6.0%) in the non-CTR group. CTR is of no
      prophylactic value for postoperative CTS in volar plated DRF patients.

PMID- 29580686
TI  - Relationship between pain and hesitation during movement initiation after distal
      radius fracture surgery: A preliminary study.
AB  - We investigated the relationship between pain and hesitation during movement
      initiation among 11 adult female patients who had undergone surgery for a distal
      radius fracture. Data on the patients' pain at rest, pain during movement and
      score on the Pain Catastrophizing Scale were analyzed. Movement characteristics
      were assessed by the administration of a finger tapping (FT) task using the thumb
      and index finger, with the movement repeated 10 times, recorded and analyzed to
      determine the patient's hesitation when opening or closing her thumb/forefinger
      during the task. Hesitation of movement initiation was significantly correlated
      with subjective factors such as pain at rest, pain during movement, and
      rumination. Pain was not significantly correlated with the physical range of
      motion. Our findings suggest that hesitation during movement initiation for the
      FT task may be a type of behavior that is affected by subjective pain. Movement
      hesitation is a novel clinical sign indicating the possible progression of acute
      pain into chronic pain. The kinematic evaluation described herein is a convenient
      clinical measurement that captures a subjective factor.

PMID- 29580687
TI  - Beadex, a Drosophila LIM domain only protein, function in follicle cells is
      essential for egg development and fertility.
AB  - LIM domain, constituted by two tandem C2H2 zinc finger motif, proteins regulate
      several biological processes. They are usually found associated with various
      functional domains like Homeodomain, kinase domain and other protein binding
      domains. LIM proteins that are devoid of other domains are called LIM only
      proteins (LMO). LMO proteins were first identified in humans and are implicated
      in development and oncogenesis. They regulate various cell specifications by
      regulating the activity of respective transcriptional complexes. The Drosophila
      LMO protein (dLMO), Beadex (Bx), regulates various developmental processes like
      wing margin development and bristle development. It also regulates Drosophila
      behavior in response to cocaine and ethanol. We have previously generated Bx null
      flies and shown its essential function in neurons for multiple aspects of female
      reproduction. However, it was not known whether Bx affects reproduction through
      its independent function in ovaries. In this paper we show that female flies null
      for Bx lay eggs with multiple defects. Further, through knock down studies we
      demonstrate that function of Bx in follicle cells is required for normal egg
      development. We also show that function of Bx is particularly required in border
      cells for Drosophila fertility.

PMID- 29580688
TI  - SIRT3 aggravates metformin-induced energy stress and apoptosis in ovarian cancer
      cells.
AB  - Increasing evidence suggests that mitochondrial respiratory chain complex I
      participates in carcinogenesis and cancer progression by providing energy and
      maintaining mitochondrial function. However, the role of complex I in ovarian
      cancer is largely unknown. In this study we showed that metformin, considered to
      be an inhibitor of complex I, simultaneously inhibited cell growth and induced
      mitochondrial-related apoptosis in human ovarian cancer cells. Metformin
      interrupted cellular energy metabolism mainly by causing damage to complex I that
      impacted mitochondrial function. Additionally, treatment with metformin increased
      the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated
      that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress
      and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3
      overexpression increased activation of AMP-activated protein kinase (AMPK), a
      major sensor of cellular energy status. AMPK compensated for energy loss by
      increasing glycolysis. The impact of this was assessed by reducing glucose levels
      in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis
      and AMPK. The combination of these factors with metformin intensified
      cytotoxicity through further downregulation of ATP. Our study outlines an
      important role for SIRT3 in the antitumor effect of mitochondrial complex I
      inhibitors in human ovarian cancer cells. This effect appears to be mediated by
      induction of energy stress and apoptosis. Strategies that target the mitochondria
      could be enhanced by modulating glycolysis to further aggravate energy stress
      that may increase the antitumor effect.

PMID- 29580689
TI  - Relationships between scalp, brain, and skull motion estimated using magnetic
      resonance elastography.
AB  - The objective of this study was to characterize the relationships between motion
      in the scalp, skull, and brain. In vivo estimates of motion transmission from the
      skull to the brain may illuminate the mechanics of traumatic brain injury.
      Because of challenges in directly sensing skull motion, it is useful to know how
      well motion of soft tissue of the head, i.e., the scalp, can approximate skull
      motion or predict brain tissue deformation. In this study, motion of the scalp
      and brain were measured using magnetic resonance elastography (MRE) and separated
      into components due to rigid-body displacement and dynamic deformation.
      Displacement estimates in the scalp were calculated using low motion-encoding
      gradient strength in order to reduce "phase wrapping" (an ambiguity in
      displacement estimates caused by the 2 pi-periodicity of MRE phase contrast). MRE
      estimates of scalp and brain motion were compared to skull motion estimated from
      three tri-axial accelerometers. Comparison of the relative amplitudes and phases
      of harmonic motion in the scalp, skull, and brain of six human subjects indicate
      that data from scalp-based sensors should be used with caution to estimate skull
      kinematics, but that fairly consistent relationships exist between scalp, skull,
      and brain motion. In addition, the measured amplitude and phase relationships of
      scalp, skull, and brain can be used to evaluate and improve mathematical models
      of head biomechanics.

PMID- 29580691
TI  - Measurement of active muscle stiffness with and without the stretch reflex.
AB  - The purpose of the present study was to evaluate active muscle stiffness with the
      stretch reflex according to changes (in 110-ms period after stretching) in torque
      and fascicle length during slower angular velocity (peak angular velocity of 100
      deg.s-1) in comparison with active muscle stiffness without the stretch reflex
      (in 60-ms period after stretching) during slower and faster (peak angular
      velocity of 250 deg.s-1) angular velocities. Active muscle stiffness in the
      medial gastrocnemius muscle was calculated according to changes in estimated
      muscle force and fascicle length with slower and faster stretching during
      submaximal isometric contractions (10-90% maximal voluntary contractions). Active
      muscle stiffness significantly increased for both angular velocities and analyzed
      periods as torque levels exerted became higher. The effects of angular velocities
      and the interaction between angular velocities and torque levels were not
      significantly different between 250 deg.s-1 (in 60-ms period after stretching)
      and 100 deg.s-1 (in 110-ms period after stretching) conditions. The effects of
      the analyzed periods and the interaction between analyzed periods and torque
      levels were not significantly different between the analyzed periods (60-ms and
      110-ms periods after stretching) for the 100 deg.s-1 condition. Furthermore,
      active muscle stiffness measured during the same angular velocity had significant
      correlations between those calculated in the different analyzed periods, whereas
      those under 250 deg.s-1 (60-ms period after stretching) did not correlate with
      those under 100 deg.s-1 (110-ms period after stretching). These results suggest
      that active muscle stiffness is not influenced by the stretch reflex.

PMID- 29580690
TI  - Opto-mechanical characterization of sclera by polarization sensitive optical
      coherence tomography.
AB  - Polarization sensitive optical coherence tomography (PSOCT) is an interferometric
      technique sensitive to birefringence. Since mechanical loading alters the
      orientation of birefringent collagen fibrils, we asked if PSOCT can be used to
      measure local mechanical properties of sclera. Infrared (1300 nm) PSOCT was
      performed during uniaxial tensile loading of fresh scleral specimens of rabbits,
      cows, and humans from limbal, equatorial, and peripapillary regions. Specimens
      from 8 human eyes were obtained. Specimens were stretched to failure at 0.01 mm/s
      constant rate under physiological conditions of temperature and humidity while
      birefringence was computed every 117 ms from cross-sectional PSOCT. Birefringence
      modulus (BM) was defined as the rate of birefringence change with strain, and
      tensile modulus (TM) as the rate of stress change between 0 and 9% strain. In cow
      and rabbit, BM and TM were positively correlated with slopes of 0.17 and 0.10
      GPa, and with correlation coefficients 0.63 and 0.64 (P < 0.05), respectively,
      following stress-optic coefficients 4.69, and 4.20 GPa-1. In human sclera, BM and
      TM were also positively correlated with slopes of 0.24 GPa for the limbal, 0.26
      GPa for the equatorial, and 0.31 GPa for the peripapillary regions. Pearson
      correlation coefficients were significant at 0.51, 0.58, and 0.69 for each
      region, respectively (<0.001). Mean BM decreased proportionately to TM from the
      limbal to equatorial to peripapillary regions, as stress-optic coefficients were
      estimated as 2.19, 2.42, and 4.59 GPa-1, respectively. Since birefringence and
      tensile elastic moduli correlate differently in cow, rabbit, and various regions
      of human sclera, it might be possible to mechanically characterize the sclera in
      vivo using PSOCT.

PMID- 29580692
TI  - Modeling the two-dimensional accuracy of soccer kicks.
AB  - In many sports, athletes perform motor tasks that simultaneously require both
      speed and accuracy for success, such as kicking a ball. Because of the
      biomechanical trade-off between speed and accuracy, athletes must balance these
      competing demands. Modelling the optimal compromise between speed and accuracy
      requires one to quantifyhow task speed affects the dispersion around a target, a
      level of experimental detail not previously addressed. Using soccer penalties as
      a system, we measured two-dimensional kicking error over a range of speeds,
      target heights, and kicking techniques. Twenty experienced soccer players
      executed a total of 8466 kicks at two targets (high and low). Players kicked with
      the side of their foot or the instep at ball speeds ranging from 40% to 100% of
      their maximum. The inaccuracy of kicks was measured in horizontal and vertical
      dimensions. For both horizontal and vertical inaccuracy, variance increased as a
      power function of speed, whose parameter values depended on the combination of
      kicking technique and target height. Kicking precision was greater when aiming at
      a low target compared to a high target. Side-foot kicks were more accurate than
      instep kicks. The centre of the dispersion of shots shifted as a function of
      speed. An analysis of the covariance between horizontal and vertical error
      revealed right-footed kickers tended to miss below and to the left of the target
      or above and to the right, while left-footed kickers tended along the reflected
      axis. Our analysis provides relationships needed to model the optimal strategy
      for penalty kickers.

PMID- 29580693
TI  - Innovative in cellulo method as an alternative to in vivo neurovirulence test for
      the characterization and quality control of human live Yellow Fever virus
      vaccines: A pilot study.
AB  - Live attenuated vaccines have proved to be mostly valuable in the prevention of
      infectious diseases in humans, especially in developing countries. The safety and
      potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing,
      must be proven before being administrated to humans. For now, the tests used to
      control vaccine safety largely involve animal testing. For live viral vaccines,
      regulations require suppliers to demonstrate the absence of neurovirulence in
      animals, principally in non-human primates and mice. In a search to reduce the
      use of animals and embracing the 3Rs principles (Replacement, Reduction,
      Refinement in the use of laboratory animals), we developed a new Blood-Brain
      Barrier Minibrain (BBB-Minibrain) in cellulo device to evaluate the
      neuroinvasiveness/neurovirulence of live Yellow Fever virus (YFV) vaccines. A
      pilot study was performed using the features of two distinct YFV strains, with
      the ultimate goal of proposing a companion test to characterize YFV
      neurovirulence. Here, we demonstrate that the BBB-Minibrain model is a promising
      alternative to consider for future replacement of YFV vaccine in vivo
      neurovirulence testing (see graphical abstract).

PMID- 29580694
TI  - Mean Right Atrial Pressure for Estimation of Left Ventricular Filling Pressure in
      Patients with Normal Left Ventricular Ejection Fraction: Invasive and Noninvasive
      Validation.
AB  - BACKGROUND: There is a paucity of data on the utility of right atrial pressure
      (RAP) for estimating pulmonary capillary wedge pressure (PCWP) in patients with
      normal ejection fraction (EF), including patients with heart failure with
      preserved EF. METHODS: Mean RAP was compared with PCWP in 129 patients (mean age,
      61 +/- 11 years; 45% men) with exertional dyspnea enrolled in a multicenter
      study. Measurements included left ventricular volumes, EF, and mitral inflow
      velocities. RESULTS: Mean PCWP was 14 +/- 7 mm Hg, and mean RAP was 8 +/- 5 mm
      Hg. A significant relation was present between mean RAP and mean PCWP (r2 = 0.5,
      P < .001). RAP > 8 mm Hg had 76% sensitivity and 86% specificity in detecting
      mean PCWP > 12 mm Hg. In 101 patients with inconclusive mitral filling pattern
      (defined according to American Society of Echocardiography/European Association
      of Cardiovascular Imaging 2016 diastolic function recommendations), RAP by
      catheterization had sensitivity of 73% and specificity of 91%. In a subset of 59
      patients with echocardiographic assessment of mean RAP, RAP by echocardiography
      had sensitivity of 76% and specificity of 89%. CONCLUSIONS: Mean RAP provides
      useful information about mean PCWP in many patients with normal left ventricular
      EF. There is good sensitivity and excellent specificity when combining invasive
      or noninvasive RAP and mitral velocities to determine if PCWP is elevated.

PMID- 29580695
TI  - Vasodilator Stress Single-Photon Emission Computed Tomography or Contrast Stress
      Echocardiography Association with Hard Cardiac Events in Suspected Coronary
      Artery Disease.
AB  - BACKGROUND: We compared the long-term outcome of subjects without prior cardiac
      disease who underwent either vasodilator single-photon emission computed
      tomography (SPECT) or contrast stress-echocardiography (cSE) for suspected
      coronary artery disease (CAD). METHODS: Subjects who underwent vasodilator SPECT
      or cSE between 2008 and 2012 for suspected CAD but no history of cardiac disease
      were included. We retrospectively compared the association of each method with
      combined all-cause death and nonfatal myocardial infarction and their positive
      predictive value (PPV) for angiographically obstructive CAD. RESULTS: A total of
      1,387 subjects were selected: 497 who underwent SPECT and 890 who underwent cSE.
      During 4 years of mean follow-up there were 78 hard events in the cSE group and
      51 in the SPECT group. Event-free survival in subjects testing positive for
      ischemia, either with SPECT or cSE, was significantly worse both in the overall
      population and after propensity matching patients. In multivariable analyses,
      vasodilator SPECT or cSE demonstrated significant stratification capability with
      an ischemic test doubling (SPECT) or more than doubling (cSE) the risk of future
      hard events independently from other variables. PPV of vasodilator SPECT for the
      diagnosis of obstructive CAD was inferior to vasodilator cSE (PPV = 63% vs 89%,
      respectively; P < .001). CONCLUSIONS: Our study suggests that the associations of
      vasodilator SPECT or cSE with outcome are comparable, with cSE demonstrating
      better diagnostic PPV for CAD. The absence of ionizing radiation and anticipated
      lower costs from higher PPV suggest that vasodilator cSE is a valid alternative
      to vasodilator SPECT as a gatekeeper in subjects without a prior history of CAD.

PMID- 29580696
TI  - Outcomes in Patients Treated with Post-mastectomy Chest Wall Radiotherapy without
      the Routine Use of Bolus.
AB  - AIMS: The use of bolus in post-mastectomy radiotherapy (PMRT) varies
      significantly between institutions. We report on chest wall recurrence and acute
      toxicity rates for PMRT patients treated with selective use of bolus. MATERIALS
      AND METHODS: We analysed PMRT patients who received adjuvant chest wall
      radiotherapy for invasive breast cancer between 2004 and 2009. Patient, tumour
      and cancer outcomes were collected from a prospective database, with additional
      radiotherapy and acute toxicity details supplemented retrospectively. Chest wall
      bolus was reserved for patients considered at high risk of local recurrence.
      RESULTS: There were 314 patients suitable for analysis: 52 received bolus, 262
      did not. The mean age was 53.2 years. The median follow-up was 4.2 years. The
      most common T stage was T2 (37%), followed by T3/T4 (33%). There were 229
      patients (73%) who had N+ disease; 213 (68%) patients had grade 3 cancer.
      Oestrogen receptor was positive in 176 (56%) cases, progesterone receptor was
      positive in 134 (43%) and HER2 receptor was positive in 24 (8%). Lymphovascular
      space invasion was present in 146 patients (46%), dermal invasion in 30 patients
      (10%) and positive margin in 14 patients (4%). The 4 year chest wall recurrence
      rate was 14% (95% confidence interval 5.4-26.8%) in the bolus group and only 3.5%
      (95% confidence interval 1.6-6.4%) in the non-bolus group. On univariate
      analysis, use of bolus was associated with a significant difference in chest wall
      recurrence (hazard ratio 3.09; 1.15-8.33; P = 0.025). However, when taking into
      account margin status, this significance was lost (hazard ratio = 2.45; 95%
      confidence interval 0.80-7.50, P = 0.12). There was a higher rate of acute grade
      2 skin toxicity in patients receiving bolus compared with those without, 40%
      versus 21% (P = 0.01). CONCLUSIONS: The selective use of bolus resulted in a
      small risk of chest wall recurrence rates for low-risk patients. This suggests
      that the routine use of bolus in PMRT patients may be unnecessary.

PMID- 29580697
TI  - Intravesical recurrence after bladder sparing treatment of small cell carcinoma
      of the bladder: Characteristics, treatment, and outcome.
AB  - INTRODUCTION: Small cell carcinoma of the bladder (SCCB) is a rare and lethal
      disease. Previously, we and others have reported a bladder sparing strategy with
      platinum-etoposide-based chemotherapy followed by radiotherapy of the bladder.
      Little is known on frequency and treatment of intravesical recurrence following
      this approach. The objective of this study is to describe the incidence of
      intravesical recurrences and their management. MATERIALS AND METHODS:
      Retrospective study including all patients with SCCB treated at a single
      institution from 1993 until 2016. All patients with limited disease (LD) SCCB who
      had a bladder sparing approach with sequential chemotherapy and radiotherapy were
      identified. Intravesical and overall recurrence rate, overall and disease
      specific survival, salvage treatment options and their results were retrieved.
      RESULTS: Of the 110 patients with SCCB (82% male) with a mean age of 65 years and
      a median follow up of 48 months, 89 patients (81%) had LD-SCCB. Of these, 65 were
      treated with chemotherapy and radiotherapy, with a median overall recurrence free
      survival of 22 months (CI: 14-30). Of 65 patients, 23 (35%) progressed to distant
      metastasis without intravesical recurrence after a median of 9 months (CI: 8-11),
      whereas 14 patients (22%) developed isolated intravesical recurrence at a median
      of 24 months (CI: 14-34). Local recurrence contained SCCB, urothelial carcinoma,
      and carcinoma in situ and was treated with various local salvage treatments
      including TURB, cystectomy, neoadjuvant chemotherapy, and BCG. Following salvage
      treatment a complete response was seen in 64%. Median overall survival for
      intravesical vs. systemic recurrence was different, with 28 (CI: 9-47) and 8 (CI:
      5-11) months, respectively (P<0.001). CONCLUSION: SCCB is a serious potentially
      lethal disease. Even in patients with LD-SCCB a high percentage rapidly develops
      systemic disease. This suggests that systemic therapy is more important than the
      type of local treatment to control the disease but small sample sizes limit the
      ability to distinguish between different treatment options in this study. A
      bladder sparing approach can be a reasonable alternative to major surgery.
      However, in those surviving long enough isolated intravesical recurrence occurs
      even after many years. Our results indicate that long term follow up is required
      because salvage therapy can be successful in the majority of patients.

PMID- 29580698
TI  - Application of HRAM screening and LC-MS/MS confirmation of active pharmaceutical
      ingredient in "natural" herbal supplements.
AB  - The growing market of herbal remedies worldwide could pose severe problems to
      consumers' health due to the possible presence of potentially harmful, undeclared
      synthetic substances or analogues of prescription drugs. The present work shows a
      simple but effective approach to unequivocally identify synthetic anorectic
      compounds in allegedly 'natural' herbal extracts, by exploiting liquid
      chromatography/time of flight (Q-TOF LC/MS) technology coupled to liquid
      chromatography/triple quadrupole (LC-MS/MS) confirmation and quantitation. The
      procedure was applied to five tea herbal extracts and pills sold as coadjutant
      for weigh loss. The method exploited liquid-liquid sample extraction (LLE) and
      separation in a C18 (2.1mm*150mm, 1.8MUm) column. QTOF acquisitions were carried
      out both in scan mode and all ion MS/MS mode and results were obtained after
      search against ad hoc prepared library. Sibutramine, 4-hydroxyamphetamine,
      caffeine and theophylline were preliminary identified samples. Confirmation and
      quantitation of the preliminary identified compounds were obtained in LC-MS/MS
      after preparation of appropriated standards. Sibutramine, caffeine and
      theophylline were finally confirmed and quantitate.

PMID- 29580699
TI  - Evaluation of two commercial methods for the susceptibility testing of Candida
      species: Vitek 2(r) and Sensititre YeastOne(r).
AB  - BACKGROUND: An increased incidence of fungal infections caused by Candida
      species, especially Candida glabrata and Candida krusei, which are less
      susceptible to azoles, has been observed. Standardized susceptibility testing is
      essential for clinical management and for monitoring the epidemiology of
      resistance. AIMS: We evaluated the performance of two different susceptibility
      testing commercial methods, Vitek 2(r) and Sensititre YeastOne(r), and compared
      them with the standard broth microdilution method (CLSI). METHODS: A total of 80
      isolates of several Candida species (Candida albicans, Candida parapsilosis
      complex, Candida tropicalis, C. glabrata and C. krusei) were selected for this
      study. RESULTS: We analyzed the categorical agreement (CA) between the methods,
      stratifying the disagreements. The average CA between the methods was 96.3% for
      Vitek 2(r) and 84% for Sensititre YeastOne(r). No very major errors were
      observed. Major errors and minor errors were found for all the isolates tested.
      With the azoles, both Vitek 2(r) and Sensititre YeastOne(r) had good and similar
      performance levels, except for C. tropicalis and C. krusei (Sensititre
      YeastOne(r) showed low CA, 56.2%). With the echinocandins, both methods showed
      good performance for C. albicans, C. parapsilosis and C. tropicalis. However, we
      observed important discrepancies for C. krusei with caspofungin: Vitek 2(r) had
      100% CA while Sensititre YeastOne(r) had only 25%. With amphotericin B, both
      Vitek 2(r) and Sensititre YeastOne(r) had good performance with high CA.
      CONCLUSIONS: Despite the limited isolates tested, we concluded that both methods
      have good performance and are reliable for antifungal susceptibility testing.
      However, caspofungin activity against C. krusei and C. glabrata should be
      interpreted carefully when using Sensititre YeastOne(r) because we observed a low
      CA.

PMID- 29580700
TI  - [Peer support programs in mental health in France: Status report and challenges].
AB  - OBJECTIVES: Recovery is a process through which people experiencing mental
      illness learn to live with their disorder and reach social insertion and
      citizenship. This positive approach focuses on a person's competencies and
      strengths rather than on the symptoms. Within this philosophy, peer support has
      been unevenly developing in mental health services worldwide with roots in the
      South-American social programs for homeless people and in the American recovery
      circles in the field of addiction. Therapeutic efficiency of peer support has
      been proven by several studies including a control group, as being at least as
      good as traditional services and even better in some specific areas such as
      reduction of need for emergency services and ability to reach "difficult"
      patients. The integration of former psychiatric services users in mental health
      services can take several forms, from the participation to scientific research
      studies to the direct involvement in a professional team at mental health
      facilities. In this context, our research aims to sum up the situation in France
      in comparison with other countries. METHODS: We conducted a worldwide literature
      review in English and in French on peer support experiences and policies in
      mental health services, using medical and psychological databases (PsycInfo,
      PsycArticles, SantePsy, Cairn, Medline, Wiley Interscience and PubPsych) on a
      recent period: 2005-2016. In total, 32 relevant scientific papers have been
      included in our research. In some cases, we have also used official reports,
      blogs, Internet sites, and mass media articles when they were relevant. RESULTS:
      Our results show that this movement has been long to develop in France, with
      controversies having been raised since the beginning on the role that peers
      should play and confusion with existing social integration programs in the
      associative sector. Drawing inspiration from the Canadian model, a recent "peer
      mentor" initiative has been analyzed after 2 years of existence: many benefits
      for services users such as the optional aspect of this care process, a more
      authentic therapeutic relationship, a less normative frame, an active
      partnership, and a more optimistic philosophy aiming to make "small steps"
      towards improvement have been reported. Health professionals and peer mentors
      themselves have found benefits during the process. However, several limits such
      as difficulties to find a place with regards to the psychiatric team and
      difficulties to take advantage of the peer specificity, resulting in a
      significant attrition of the number of peer mentors, could be observed. A few
      other important initiatives focused on social insertion and using the help of
      professional peer support have been developed in recent years, but they seem to
      have encountered the same issues about positioning themselves both in terms of
      day-to-day integration in the professional environment and in the job title given
      by institutions which rarely corresponds to their experience and specificity. In
      addition, it remains difficult to obtain reliable information, as only a few
      papers have been published on this matter. Also, while some evaluation studies
      are currently being carried out, independent quantitative studies of the few
      running programs seem to lack in this field. CONCLUSIONS: In our presentation,
      taking into account the difficulties that were raised in French programs and the
      lessons of practical experiences at work in other countries, we propose
      recommendations for larger and more effective implementations of peer support
      programs in France. As this new kind of care is emerging and seems promising in
      terms of benefits for not only the users but also the peer supporters and the
      teams of health professionals, we also insist on the need for a systematic
      scientific and objective evaluation of the programs.

PMID- 29580701
TI  - Facial emotion recognition in children with or without Attention
      Deficit/Hyperactivity Disorder: Impact of comorbidity.
AB  - OBJECTIVES: This study sought to assess facial emotion recognition deficit in
      children with Attention Deficit/Hyperactivity Disorder (ADHD) and to test the
      hypothesis that it is increased by comorbid features. METHOD: Forty children
      diagnosed with ADHD were compared with 40 typically developing children, all aged
      from 7 to 11years old, on a computerized facial emotion recognition task (based
      on the Pictures of Facial Affect). Data from parents' ratings of ADHD and
      comorbid symptoms (on the Conners' Revised Parent Rating Scale) were also
      collected. RESULTS: Children with ADHD had significantly fewer correct answer
      scores than typically developing controls on the emotional task while they
      performed similarly on the control task. Recognition of sadness was especially
      impaired in children with ADHD. While ADHD symptoms were slightly related to
      facial emotion recognition deficit, oppositional symptoms were related to a
      decrease in the number of correct answers on sadness and surprise recognition.
      CONCLUSION: Facial emotion recognition deficit in children with ADHD might be
      related to an impaired emotional process during childhood. Moreover, Oppositional
      Defiant Disorder seems to be a risk factor for difficulties in emotion
      recognition especially in children with ADHD.

PMID- 29580702
TI  - [Methods to improve suicidal adolescents' compliance to care after emergency
      discharge: A literature review].
AB  - OBJECTIVES: Suicidal adolescents admitted in an Emergency Department (ED) present
      a high risk of suicidal reattempts. Poor observance of follow-up in this
      particular group imped the efficacity of the treatment. We propose to summarize
      the international literature on ED interventions promoting suicidal adolescents'
      adherence to care. METHOD: We carried out a comprehensive review of papers listed
      in PubMed, PsycInfo, and CINHAL databases using keywords about adolescence,
      suicide, and ED. We also manually consulted the main journals specialized in
      suicidology (Crisis and Suicide and Life-Threatening Behavior) and adolescence
      (Journal of the American Academy of Child and Adolescent Psychiatry, Journal of
      Adolescent Health, Neuropsychiatrie de l'Enfance et de l'Adolescence). We
      selected the relevant articles describing or evaluating one or more interventions
      initiated in the ED and designed to promote adolescent adherence to post
      emergency care. The results are presented in a narrative review form. RESULTS:
      Interventions are organized in three groups: interventions that take place solely
      at the ED (problem-solving interventions and educational interventions directed
      to families) and interventions that take place during and after emergency care
      (we included in this group the ED-Care program, the FISP program, and the SAFETY
      program), to which should be added interventions that take place prior to care,
      in particular specific trainings for medical and paramedical teams. Small samples
      and barriers in measuring adherence to care make statistical comparisons
      difficult, yet the interventions that seem most effective are those that target
      the time both during and after ED discharge, those which are implemented most
      rapidly after discharge, those which actively include parents, and those which
      involve an implication of the families about barriers to follow-up. CONCLUSION:
      Our results show an effectiveness of complete programs on short-term compliance
      but no conclusion can be drawn on long-term effects. Most comprehensive care
      programs are based on the principle of adolescent compliance, which remains
      problematic. Until today, no ideal protocol exists to improve short-term as well
      as long-term compliance to care among adolescents after a suicide attempt. We
      have to improve our understanding of facilitators and barriers to follow-up using
      quantitative as well as qualitative research studies. Although it is well
      established that parents' involvement in the early stages of care is essential,
      little is known about the underlying processes. In these situations, qualitative
      studies could help to better target interventions that lead more particularly to
      follow up compliance in adolescence.

PMID- 29580703
TI  - [Delusional misidentification syndromes: A factor associated with violence?
      Literature review of case reports].
AB  - OBJECTIVES: Delusional misidentification syndromes (DMS) correspond to the
      delusional belief of misidentification of familiar persons, places or objects and
      to the conviction that they have been replaced or transformed. Several cases of
      patients who developed violent behavior while suffering from DMS have been
      published. This led some authors to consider patients with DMS at risk of
      violence. However, only a few studies have focused on the potential relationship
      between violence and DMS. The aim of our study was to explore this relationship
      with a literature review of published cases of patients having committed violent
      acts associated to DMS. METHODS: A systematic literature search was conducted on
      PubMed up to January 2017 using the following term combination
      "misidentification" and "violence" Fifteen cases of patients with DMS who had
      committed violent acts were identified. The data from these descriptions were
      analyzed and synthetized. RESULTS: Most of the patients were men with a diagnosis
      of schizophrenia and Capgras syndrome. Acts of violence were severe with a
      relatively high number of murders or attempted murders. For half of the patients
      these violent acts were perpetrated with weapons. Victims were regularly the
      patient's family members and the assaults were usually not planned. Delusional
      syndromes often progressed for several years. Importantly, substance abuse, which
      is known to increase the risk of violence in patients with schizophrenia, was
      only observed in two patients. CONCLUSION: DMS are associated with several risk
      factors of violence, such as a diagnosis of schizophrenia, specific delusions
      including megalomania, persecution, negative affects and identified targets.
      Despite this risk for severe violence, there are no existing guidelines on how to
      assess and treat DMS in schizophrenia. Accordingly, we propose (1) the
      establishment of formal diagnostic criteria, (2) the development of rigorous
      research on these syndromes and (3) the integration of DMS in assessment of
      violence risk in schizophrenic patients.

PMID- 29580704
TI  - On cognitive debiasing and the judgment of suicide-attackers.
AB  - Suicide-attacks are possibly increasing in frequency all over the world. To date,
      these attacks are not considered as a manifestation of a particular mental
      illness. However, the process of radicalization of suicide-attackers has to
      interest the field of mental health. One plausible explanation for the
      radicalization of individuals is the use of biased cognitive schemes by the
      indoctrinator. Among these cognitive schemes could figure the causal attribution
      bias in which the subject cannot distinguish in front of two factors that operate
      simultaneously, the share of each factor in achieving a certain goal. Another
      cognitive bias would be the confirmation bias during which the subject would tend
      to adhere to ideas from his/her own thinking or the thinking of subjects who
      share some cultural values with him/her and refute any other ideas. Finally, the
      bias of polarization or splitting could also be incriminated. Through this bias,
      the subject would either be proud of being a member of a cultural group or
      ashamed when he/she feels that this group is being attacked and that he/she is
      unable to rescue it. Approaches to increase the awareness of individuals to the
      adverse effects of these biased cognitive schemes may theoretically reduce the
      risk of committing suicide-attacks. However, despite numerous attempts of
      "deradicalization" involving technological means of communication as well as
      social "reintegration" centers, all approaches aiming at raising awareness of
      cognitive biases need to be studied in a scientific manner before they become
      widespread.

PMID- 29580705
TI  - [Consultation/liaison addiction medicine: Tools and specificities].
AB  - Since the 1970s, the concept of "consultation/liaison (CL) psychiatry" has
      pertained to specialized mobile teams which meet inpatients hospitalized in non
      psychiatric settings to offer them on-the-spot psychiatric assessment, treatment,
      and, if needed, adequate referral. Since the birth of CL psychiatry, a long set
      of theoretical books and articles has aimed at integrating CL psychiatry into the
      wider scope of psychosomatic medicine. In the year 2000, a circular issued by the
      Health Ministry defined the organization of "CL addiction services" in France.
      Official CL addiction teams are named "Equipes de Liaison et de Soins en
      Addictologie" (ELSAs) which are separated from CL psychiatry units. Though this
      separation can be questioned, it actually emphasizes that the work provided by CL
      addiction teams has some very specific features. The daily practice of ELSAs
      somewhat differs from that of psychiatric CL teams. Addictive behaviors often
      result from progressive substance misuse. In this respect, the ELSAs' practice
      frequently involves screening, brief intervention, and referral to treatment
      (SBIRT) interventions, which are rather specific of addiction medicine and
      consist more of prevention interventions than actual addiction treatment.
      Moreover, for patients with characterized substance use disorders substantial
      skills in motivational interviewing are required in ELSA consultations. Though
      motivational interviewing is not specific to addiction medicine, its regular use
      is uncommon for other liaison teams in France. Furthermore, substance misuse can
      induce many types of acute or delayed substance-specific medical consequences.
      These consequences are often poorly known and thus poorly explored by physicians
      of other specialties. ELSAs have therefore the role of advising their colleagues
      for a personalized somatic screening among patients with substance misuse. In
      this respect, the service undertaken by ELSAs is not only based on relational
      skills but also comprises a somatic expertise. This specificity differs from CL
      psychiatry. Moreover, several recent studies have shown that in some cases it was
      useful to extend liaison interventions for addiction into outpatient
      consultations that are directly integrated in the consultation units of certain
      specialties (e.g., hepatology, emergency, or oncology). Such a partnership can
      substantially enhance patients' motivation and addiction outcome. This
      specificity is also hardly transposable in CL psychiatry. In France, addiction
      medicine is an inter-specialty that is not fully-integrated into psychiatry. This
      separation is also applied for CL services which emphasizes real differences in
      the daily practices and in intervention frameworks. Regardless, CL psychiatry
      units and ELSAs share many other features and exhibit important overlaps in terms
      of targeted populations and overall missions. These overlaps are important to
      conjointly address, with the aim to offer integrated and collaborative services,
      within the hospital settings of other medical specialties.

PMID- 29580706
TI  - [Predictive factors of seclusion duration in patients hospitalized in psychiatry
      settings. A prospective multisite study in the DTRF Paris-Sud].
AB  - INTRODUCTION: In psychiatric inpatient settings seclusion is a last resort to
      ensure the safety of the patient, other patients, and staff from disturbed
      behaviors. Despite its major interest for patients, seclusion could negatively
      impact treatment adherence and patient/staff relationships. Indeed, some secluded
      patients report a feeling of guilt during the measure and do not consider
      seclusion to be a healthcare intervention. To be more beneficial and to reduce
      the feeling by patients of being forced, seclusions should be as short and rare
      as possible. In other words, measures to reduce seclusion are available and have
      been clearly identified. Such measures could be applied, in the first instance,
      in patients with longer duration. In this way, the aim of this study was to
      investigate predictive factors of a seclusion of long duration. METHODS: Our
      study was based on the dataset of the EPIC study, an observational prospective
      French multicenter study of seclusion and restraint. The EPIC study occurred in
      seven French psychiatric hospitals in the southern region of Paris. Inclusions
      were realized for 73days and allowed a data collection of 302 seclusion measures.
      Of these measures 236 were effectively a seclusion in a standardized room.
      Because the median duration was 7days, we defined two groups of patients:
      duration<7days and duration >= 7 days. Our variable to be explicated was duration
      >= 7 days. Explicative variables available in EPIC study were age, sex, forced
      hospitalization, autoagressivity, heteroagressivity, use of sedative treatment
      (oral or intramuscular), history of seclusion and patient diagnoses. We used
      bivariate and multivariate analyses to explore the association between a
      seclusion duration >= 7 days and explicative variables. Diagnoses were classified
      as psychotic disorders, mood disorders and others diagnoses. To be included in
      multivariate logistic regressions, diagnoses were treated as dummy variables
      (mood disorder vs psychotic disorders; psychotic disorders vs others; mood
      disorders vs others). Statistical analyses were performed using SPSS software
      20.0 and R 3.4.0. RESULTS: Of the 236 measures of seclusion the mean age was 38.2
      (+/-12.8), 196 (83%) patients were forcibly hospitalized prior to their
      seclusion, 147 (62%) had a diagnosis of psychotic disorder, 43 (18%) a diagnosis
      of mood disorder and 33 (14%) an "other diagnosis". Mean duration was 10.2 (1.5)
      days and median was 7.1 days. One hundred and thirty-five (47%) patients were in
      the group of duration >= 7 days. In bivariate analyses, variables associated with
      a duration >= 7 days were: being in forced hospitalization prior to the seclusion
      (P=0.04), administration of a sedative treatment (P=0.01) and against the group
      of others diagnoses the diagnosis of mood disorders (P<0.0005) and psychotic
      disorders (P=0.001). Multivariate analyses showed that, against the group of
      other diagnoses, the group of psychotic disorders [OR=3.3, CI 95% (1.3-8.4),
      P=0.01], the group of mood disorder [OR=2.7, CI 95% (1.4-4.9), P=0.002] and
      administration of sedative treatment [OR=8.1, CI 95% (2.0-32.5), P=0.003] were
      significantly associated with a duration >= 7 days. These results were
      independent from other confusion variables. Considering the hospitalization
      status, psychotic disorders was the only diagnosis which showed an association
      between duration >= 7 days and forced hospitalization [OR=2.9 CI 95% (1.1-7.8),
      P=0.03]. CONCLUSION: Our study highlighted two profiles of higher risk to remain
      >= 7days in seclusion. The first one is patients with a diagnosis of mood
      disorder who needed sedative treatment. The second one is patients with a
      diagnosis of psychotic disorder who needed sedative treatment and forced
      hospitalized before seclusion. Thus, these two profiles could be a good target to
      practice, in the first instance, measures to reduce seclusion duration in
      psychiatry settings.

PMID- 29580707
TI  - Improving quality of psychiatric care in Latvia by measuring patient experiences.
AB  - In Latvia, as in many former Soviet Union countries, there used to be little
      priority given to systematic assessments of the quality of psychiatric care.
      Furthermore, using the experiences of patients as a measure of quality was
      unthinkable because psychiatric patients were seen as incapable of assessing
      quality of psychiatric services. Over the past few years, and facilitated by
      Latvia's progress along the route of Western democracy and participation in
      international organizations (EU, OECD), as well as funding support from the EU,
      several policy documents have been developed with the aim of improving healthcare
      quality. Simultaneously, several small-scale initiatives have emerged aiming at
      the promotion of quality of care, such as the quality award, and the quality
      comparison of psychiatric hospitals. Furthermore, the Psychiatric Inpatient
      Patient Experience Questionnaire for on-site measurement (PIPEQ-OS) has recently
      been adapted for use in Latvia. The first application of PIPEQ-OS in a
      psychiatric hospital in Riga reveals high patient responsiveness, interest and
      surprise about being asked to participate in the decision-making process
      regarding treatment and pharmaceutical choices. More widespread use of the PIPEQ
      OS has considerable potential for (1) improving information about treatment
      shortcomings from the patients' perspective and (2) improving the treatment
      process by opening doors of cooperation with patients and changing deep-rooted
      paradigms.

PMID- 29580708
TI  - Evolving management and patient choice in pulmonary alveolar proteinosis.

PMID- 29580709
TI  - Impact of Surgical Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive
      Systematic Review and Meta-Analysis.
AB  - PURPOSE: Utilization of robotic partial nephrectomy has increased significantly.
      We report a literature wide systematic review and cumulative meta-analysis to
      critically evaluate the impact of surgical factors on the operative,
      perioperative, functional, oncologic and survival outcomes in patients undergoing
      robotic partial nephrectomy. MATERIALS AND METHODS: All English language
      publications on robotic partial nephrectomy comparing various surgical approaches
      were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic
      Review and Meta-Analyses) statement and AHRQ (Agency for Healthcare Research and
      Quality) guidelines to evaluate PubMed(r), Scopus(r) and Web of ScienceTM
      databases (January 1, 2000 to October 31, 2016, updated June 2017). Weighted mean
      difference and odds ratio were used to compare continuous and dichotomous
      variables, respectively. Sensitivity analyses were performed as needed. To
      condense the sheer volume of analyses, for the first time data are presented
      using novel summary forest plots. The study was registered at PROSPERO
      (https://www.crd.york.ac.uk/prospero/, ID CRD42017062712). RESULTS: Our meta
      analysis included 20,282 patients. When open partial nephrectomy was compared to
      robotic partial nephrectomy, the latter was superior for blood loss (weighted
      mean difference 85.01, p  <0.00001), transfusions (OR 1.81, p <0.001),
      complications (OR 1.87, p <0.00001), hospital stay (weighted mean difference
      2.26, p = 0.001), readmissions (OR 2.58, p = 0.005), percentage reduction of
      latest estimated glomerular filtration rate (weighted mean difference 0.37, p =
      0.04), overall mortality (OR 4.45, p <0.0001) and recurrence rate (OR 5.14, p
      <0.00001). Sensitivity analyses adjusting for baseline disparities revealed
      similar findings. When robotic partial nephrectomy was compared to laparoscopic
      partial nephrectomy, the former was superior for ischemia time (weighted mean
      difference 4.21, p <0.0001), conversion rate (OR 2.61, p = 0.002), intraoperative
      (OR 2.05, p >0.0001) and postoperative complications (OR 1.27, p = 0.0003),
      positive margins (OR 2.01, p <0.0001), percentage decrease of latest estimated
      glomerular filtration rate (weighted mean difference -1.97, p = 0.02) and overall
      mortality (OR 2.98, p = 0.04). Hilar control techniques, selective and unclamped,
      are effective alternatives to clamped robotic partial nephrectomy. An important
      limitation is the overall suboptimal level of evidence of publications in the
      field of robotic partial nephrectomy. No level I prospective randomized data are
      available. Oxford level of evidence was level II, III and IV in 5%, 74% and 21%
      of publications, respectively. No study has indexed functional outcomes against
      volume of parenchyma preserved. CONCLUSIONS: Based on the contemporary
      literature, our comprehensive meta-analysis indicates that robotic partial
      nephrectomy delivers mostly superior, and at a minimum equivalent, outcomes
      compared to open and laparoscopic partial nephrectomy. Robotics has now matured
      into an excellent approach for performing partial nephrectomy for renal masses.

PMID- 29580710
TI  - Extreme delta - With or without brushes: A potential surrogate marker of disease
      activity in anti-NMDA-receptor encephalitis.
AB  - OBJECTIVE: Anti-NMDA receptor encephalitis (NMDARE) may not respond to first line
      immunotherapy. Biomarkers to track disease course and guide escalation of
      immunotherapy are needed. We describe the evolution of EEG in four patients with
      NMDARE requiring prolonged intensive care. METHODS: Within a database of 121
      patients with immune-mediated neurological disorders, ten with NMDARE were
      retrospectively identified. Four patients did not respond to first line
      immunotherapy. Continuous EEG was reviewed and correlated with clinical status
      and treatment. RESULTS: Intermittent polymorphic delta slowing was present in all
      patients. Generalized rhythmic delta occupied increasing proportion of the EEG as
      disease progressed, at times with superimposed beta. The institution of second
      line immunotherapy was followed by progressive decrease in rhythmic delta,
      predating clinical improvement. In one patient who did not respond to second line
      immunotherapy, rhythmic delta continued to occupy a majority of the recording.
      The extreme delta pattern was not seen in a comparison cohort of patients with
      autoimmune encephalitis without anti-NMDA-R antibodies. CONCLUSIONS: Extreme
      delta, with or without brushes, increases with progression of NMDARE, responds to
      escalation of immunotherapy, predating clinical improvement, and is likely
      specific to NMDA-R antibodies. SIGNIFICANCE: Extreme delta may be a surrogate
      marker of disease activity in NMDARE refractory to first line immunotherapy.

PMID- 29580711
TI  - Clinical Outcomes after Pulmonary Cryoablation with the Use of a Triple Freeze
      Protocol.
AB  - PURPOSE: To elucidate clinical variables associated with safety and efficacy in
      patients after cryoablation of pulmonary tumors with the use of a triple freeze
      protocol. MATERIALS AND METHODS: Percutaneous cryoablation of pulmonary tumors
      was performed using Galil Medical cryoprobes (Arden Hills, Minnesota) with a
      triple freeze protocol: 67 nodules in 42 patients were treated at a single
      institution from 2012 to 2016. Average nodule diameter was 1.6 cm (range 0.4
      5.9); 13 nodules (19.4%) were pathologically determined to be a primary lung
      malignancy, whereas 54 (80.6%) were metastatic nodules of extrapulmonary origin.
      Average patient age was 68.1 years (range 39.6-89.6), and the male-female ratio
      was 1.3:1. Ipsilateral thoracic surgery, intervention, or radiotherapy had been
      performed before the first cryoablation in 18 patients (42.9%). Mean imaging
      follow-up was 326 days (range 9-1,152). RESULTS: Pneumothorax occurred in 19
      cases (33.9%), 7 (12.5%) requiring chest tube, the likelihood of which was
      significantly greater in patients with 3 or more cryoprobes (P < .01). Local
      tumor recurrence/residual disease occurred in 6 cases (9.0%). Local tumor
      recurrence was not seen after ablation of nodules measuring <1.0 cm at the time
      of procedure, a significant difference from the recurrence ratee of 14.3% for
      nodules measuring >=1.0 cm (P < .05). Likelihood of tumor recurrence/residual
      disease did not correlate with tumor pathology, tumor location, or procedural
      factors. The estimated marginal probabilities of local recurrence were 11.4%,
      11.4%, and 38.1% at 1, 2, and 3 years after ablation, respectively. CONCLUSIONS:
      Cryoablation of pulmonary tumors with the use of a triple freeze protocol is a
      viable modality with low recurrence and complication rates.

PMID- 29580712
TI  - Prostatic Artery Embolization in the Treatment of Localized Prostate Cancer: A
      Bicentric Prospective Proof-of-Concept Study of 12 Patients.
AB  - PURPOSE: To provide initial data on tumoricidal efficacy of embolization on
      prostate cancer via histopathologic examination of prostatectomy specimens after
      embolization. MATERIALS AND METHODS: In this bicentric prospective trial, 12 men
      with localized prostate cancer underwent radical prostatectomy 6 weeks after
      prostatic artery embolization (PAE) from October 2016 to May 2017. PAE was
      performed with the use of 100-MUm Embozene microspheres (Boston Scientific,
      Natick, Massachusetts). Response of prostate cancer tissue to PAE was assessed
      according to tumor regression grades. The major outcome measure was complete
      histopathologic absence of viable cancer cells, including secondary foci, in the
      prostatectomy specimens. RESULTS: Complete necrosis of the index lesion was found
      in 2 patients and partial necrosis in 5. Considering secondary cancerous foci,
      viable cancer cells were found in all 12 patients. Pathologic specimens were
      characterized by demarcated zones of necrotic tissue predominantly located in the
      central gland. Two patients required additional surgery to remove necrotic
      bladder tissue caused by PAE. CONCLUSIONS: PAE with the use of 100-MUm
      microspheres failed to achieve complete elimination of tumor cells. Extensive
      tumor regression was induced in some lesions, highlighting the need for further
      assessment of PAE as a potential treatment option for prostate cancer.

PMID- 29580713
TI  - Effect of statin therapy on plasma apolipoprotein CIII concentrations: A
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Statins are well-established low-density lipoprotein cholesterol
      lowering drugs. Elevated apolipoprotein CIII (Apo CIII) levels are associated
      with elevated triglyceride-rich particles, which are also considered to be a
      possible risk factor for cardiovascular disease. OBJECTIVE: The aim of this meta
      analysis of randomized placebo-controlled clinical trials was to assess the
      effect of statins on Apo CIII concentrations. METHODS: Randomized placebo
      controlled trials investigating the impact of statin treatment on cholesterol
      lowering that include lipoprotein measurement were searched in PubMed, MEDLINE,
      Scopus, Web of Science, and Google Scholar databases (up to July 31, 2017). 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 Apo CIII concentrations. RESULTS:
      This meta-analysis of data from 6 randomized placebo-controlled clinical trials
      (10 statin arms) involving 802 subjects showed that statin therapy significantly
      decreased circulating Apo CIII concentrations (weighted mean difference [WMD]: 
      2.71, 95% confidence interval [CI]: -3.74 to -1.68, P < .001; I2: 73.83%). The
      effect size was robust in the leave-one-out sensitivity analysis and not driven
      by any single study. Subgroup analysis showed a reduction of Apo CIII
      concentrations by atorvastatin (WMD: -4.74, 95% CI: -3.74 to -1.68, P = .002; I2:
      84.02%), rosuvastatin (WMD: -2.68, 95% CI: -4.52 to -0.84, P = .004; I2: 0%), and
      lovastatin (WMD: -1.64, 95% CI: -2.22 to -1.07, P < .001; I2: 0%). CONCLUSION:
      This meta-analysis suggests that statin treatment significantly reduces plasma
      Apo CIII levels.

PMID- 29580715
TI  - Response: Artificial blastocoel collapse of human blastocysts before
      vitrification and its effect on re-expansion after warming.

PMID- 29580714
TI  - Controllable and uncontrollable stress differentially impact pathogenicity and
      survival in a mouse model of viral encephalitis.
AB  - Intranasal instillation of vesicular stomatitis virus (VSV) into mice given
      controllable stress (modeled by escapable foot shock, ES) resulted in enhanced
      pathogenicity and decreased survival relative to infected mice given
      uncontrollable stress (modeled by inescapable foot shock, IS) and non-shocked
      control mice. Survival likely reflected differential cytokine gene expression
      that may have been regulated by miR146a, a predicted stress-responsive upstream
      regulator. Controllability also enhanced the accumulation of brain T resident
      memory cells that persisted long after viral clearance. The unexpected
      facilitatory effect of ES on antiviral neuroimmune responses and pathogenicity
      may arise from differential immunoactivating and immunosuppressive effects of
      uncontrollable and controllable stress.

PMID- 29580716
TI  - Image Gently(r) at 10 Years.

PMID- 29580717
TI  - National Trends in the Utilization of Skeletal Radiography From 2003 to 2015.
AB  - PURPOSE: Examine recent trends in the use of skeletal radiography and assess the
      roles of various nonradiologic specialties in the interpretations. METHODS:
      Medicare Part B fee-for-service claims data files from 2003 to 2015 were analyzed
      for all Current Procedural Terminology, version 4 (CPT-4) procedure codes related
      to skeletal radiography. The files provide examination volume, and we calculated
      utilization rates per 1,000 Medicare beneficiaries. Medicare's physician
      specialty codes were used to determine the specialties of the providers. Total
      utilization rate trends were analyzed, as well as those for radiologists and
      nonradiologists. We determined which nonradiologist specialties were the highest
      users of skeletal radiography. Medicare place-of-service codes were used to
      identify the locations where the services were provided. RESULTS: The total
      utilization rate per 1,000 of skeletal radiography within the Medicare population
      increased 9.5% from 2003 to 2015. The utilization rate for radiologists increased
      5.5% from 2003 to 2015 versus 11.1% for nonradiologists as a group. Among
      nonradiologist specialties in all health care settings over the study period,
      orthopedic surgeons increased 10.6%, chiropractors and podiatrists together
      increased 14.4%, nonphysician providers (primarily nurse practitioners and
      physician assistants) increased 441%, and primary care physicians' rate decreased
      33.5%. Although radiologists do almost all skeletal radiography interpretation in
      hospital settings, nonradiologists do the majority in private offices. There has
      been strong growth in skeletal radiography in emergency departments, but a
      substantial drop in inpatient settings. CONCLUSIONS: The utilization of skeletal
      radiography has increased more rapidly among nonradiologists than among
      radiologists. This raises concerns about self-referral and quality.

PMID- 29580718
TI  - Burden of Illness Associated with Tenosynovial Giant Cell Tumors.
AB  - PURPOSE: Little is known about the burden of illness in patients with
      tenosynovial giant cell tumors (TGCT), which are rare, typically benign, lesions
      of the synovial tissue including giant cell tumor of the tendon sheath (GCT-TS)
      and pigmented villonodular synovitis (PVNS). The objective of this study was to
      describe health care resource use and costs for patients with GCT-TS and PVNS,
      which are rare and typically benign TGCT. METHODS: A retrospective cohort study
      design was used to analyze administrative claims for adult commercial and
      Medicare Advantage health plan enrollees with evidence of GCT-TS and PVNS from
      January 1, 2006 through March 31, 2015. Participants were continuously enrolled
      for 12 months before (pre-index period) and 12 months after (post-index period)
      the date of the first tenosynovial giant cell tumor (TGCT) claim (index date).
      Preindex and postindex measures were compared using the McNemar test and Wilcoxon
      signed-rank test. Results were stratified by TGCT type. FINDINGS: The study
      identified 4664 patients with TGCT, 284 with GCT-TS, and 4380 with PVNS. Mean age
      (GCT-TS group: 50 years; PVNS group: 51 years) and sex distributions (GCT-TS
      group: 60.2% female; PVNS group: 59.5% female) were similar for each group. Most
      patients with GCT-TS (78.2%) had at least one postindex surgery, compared with
      38.7% of patients with PVNS. Mean total health care costs increased from $8943 in
      the preindex period to $14,880 in the postindex period (P < 0.001) for GCT-TS and
      from $13,221 in the preindex period to $17,728 in the postindex period (P <
      0.001) for PVNS. Preindex to postindex ambulatory costs increased nearly 120% for
      patients with GCT-TS ($4340 to $9570, P < 0.001) and 50% for patients with PVNS
      ($6782 to $10,278, P < 0.001), and physical therapy use increased significantly
      during the same period (GCT-TS: 18% to 40%, P < 0.001; PVNS: 38% to 60%, P <
      0.001). IMPLICATIONS: Costs increased substantially 1 year after the first TGCT
      claim, with more than half the costs covering ambulatory care. These results
      suggest a high health care burden once TGCT is identified.

PMID- 29580719
TI  - The toxicity of E-cigarettes and children's respiratory health.
AB  - Electronic cigarettes (E-cig), also referred to as Electronic Nicotine Delivery
      System (ENDS), were initially developed in 2003 to reduce the harmful effects of
      tobacco smoking. Since then, E-cig have become widely available in many countries
      and are used by many young people who would be unlikely to take up cigarette
      smoking. However, the adverse effects on child health remain largely unknown. E
      cigs are available through regulated sale in many countries, but easily
      accessible by the internet in others. Adverse effects may be ascribed to the
      nicotine itself, to the accompanying substances in the aerosol (often referred to
      as vapour) or to temperature modifications of the content. There is a lack of
      human studies to assess respiratory effects of nicotine exposure to the unborn or
      young child. Also assessing the effects of the vaping content apart from nicotine
      is challenging, with the huge variety of exposure by frequency, duration and
      content, but experimental studies are on the way that may indicate the level of
      harm by such products. This article will summarize what is currently known about
      the use of E-cigs in children and in pregnancy, and discuss adverse effects of
      direct or in utero exposure to E-cig on the respiratory health of children. We
      thereby hope to provide a background for discussing potential harms to the
      respiratory system of children by E-cig exposure in pregnancy and early post
      natal life, in a setting where an increasing proportion of adolescent and young
      adults use E-cigs, marketed to be 95% less harmful than conventional cigarettes.

PMID- 29580720
TI  - [Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series
      of 86 consecutive patients].
AB  - INTRODUCTION: The endoscopic endonasal approach has become the gold standard for
      the surgical treatment of pituitary adenomas. OBJECTIVES: The aim of this study
      is to present the results obtained in our hospital in purely endoscopic surgery
      of pituitary adenomas. METHODS: From February 2011 to August 2016, we conducted a
      prospective study on a series of 86 patients with pituitary adenoma, all of whom
      underwent surgery with a purely endoscopic endonasal approach. The 'four hands
      two nostrils' technique was performed in all cases by a surgical team composed of
      an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients
      were evaluated according to clinical, radiological and endocrinological criteria.
      RESULTS: In our series, 53% were women and 47% men. The age ranged from 14 to 84
      years of age, with a mean of 54 years of age. The most common initial symptom was
      visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly
      being the most common clinical syndrome. The most common tumours were non
      functioning tumours (73%), while GH-secreting tumours (65%) were the most common
      functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11%
      microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited
      suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp
      grade >=3). Total excision was achieved in 77% of the cases. After the
      intervention, visual improvement was achieved in 91% and remission of endocrine
      hyperfunction in up to a 73% of cases. The most common complication was anterior
      pituitary insufficiency of at least one axis (9%). There were no cases of
      postoperative cerebrospinal fluid fistula. CONCLUSIONS: In terms of surgical
      quality, our results are similar to those of published series, and demonstrate
      the efficacy and safety of the endoscopic endonasal approach as the surgical
      treatment of choice for pituitary adenomas. However, further studies with a
      higher sample size are necessary to obtain clinically significant results.

PMID- 29580721
TI  - Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped
      individuals with late-stage age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is associated with the formation of sub
      retinal pigment epithelial (RPE) deposits that block circulatory exchange with
      the retina. The factors that contribute to deposit formation are not well
      understood. Recently, we identified the presence of spherular hydroxyapatite
      (HAP) structures within sub-RPE deposits to which several AMD-associated proteins
      were bound. This suggested that protein binding to HAP represents a potential
      mechanism for the retention of proteins in the sub-RPE space. Here we performed
      quantitative proteomics using Sequential Window Acquisition of all THeoretical
      fragment-ion spectra-Mass Spectrometry (SWATH-MS) on plasma samples from 23
      patients with late-stage neovascular AMD following HAP-binding. Individuals were
      genotyped for the high risk CFH variant (T1277C) and binding to HAP was compared
      between wild type and risk variants. From a library of 242 HAP binding plasma
      proteins (1% false discovery rate), SWATH-MS revealed significant quantitative
      differences in the abundance of 32 HAP-binding proteins (p < 0.05) between the
      two homozygous groups. The concentrations of six proteins (FHR1, FHR3, APOC4,
      C4A, C4B and PZP) in the HAP eluted fractions and whole plasma were further
      analysed using ELISA and their presence in sections from human cadaver eyes was
      examined using immunofluorescence. All six proteins were found to be present in
      the RPE/choroid interface, and four of these (FHR1, FHR3, APOC4 and PZP) were
      associated with spherules in sub-RPE space. This study provides qualitative and
      quantitative information relating to the degree by which plasma proteins may
      contribute to sub-RPE deposit formation through binding to HAP spherules and how
      genetic differences might contribute to deposit formation.

PMID- 29580722
TI  - High-temperature Requirement Protein A1 Regulates Odontoblastic Differentiation
      of Dental Pulp Cells via the Transforming Growth Factor Beta 1/Smad Signaling
      Pathway.
AB  - INTRODUCTION: Dentinogenesis includes odontoblast differentiation and
      extracellular matrix maturation as well as dentin mineralization. It is regulated
      by numerous molecules. High-temperature requirement protein A1 (HtrA1) plays
      crucial roles in bone mineralization and development and is closely associated
      with the transforming growth factor beta (TGF-beta) signal in osteogenesis
      differentiation. Simultaneously, the TGF-beta1/small mother against
      decapentaplegic (Smad) signaling pathway is an important signaling pathway in
      various physiological processes and as a downstream regulation factor of HtrA1.
      However, the role of HtrA1 and its relationship with the TGF-beta1/Smad signaling
      pathway in dentin mineralization is unknown. METHODS: We detected the role of
      HtrA1 and its relationship with the TGF-beta1/Smad signaling pathway in
      odontoblastic differentiation of human dental pulp cells (hDPCs) in this study.
      First, hDPCs were cultured in mineralized medium, and odontoblastic
      differentiation was confirmed by investigating mineralized nodule formation,
      alkaline phosphatase (ALP) activity, and the expression of mineral-associated
      genes, including ALP, collagen I, and dentin sialophosphoprotein. Then, the
      expression of HtrA1 and TGF-beta1/Smad in hDPCs was investigated in hDPCs during
      mineralized induction. After HtrA1 knockdown by lentivirus, the mineralized
      nodule formation, ALP activity, and expression of mineral-associated genes and
      TGF-beta1/Smad genes were investigated to confirm the effect of HtrA1 on
      odontoblastic differentiation and its relationship with the TGF-beta1/Smad
      signaling pathway. RESULTS: The expression of HtrA1 and TGF-beta1 was increased
      during odontoblastic differentiation of hDPCs along with the messenger RNA
      expression of downstream factors of the TGF-beta1/Smad signaling pathway. In
      addition, lentivirus-mediated HtrA1 knockdown inhibited the process of
      mineralization and the expression of HtrA1 and TGF-beta1/Smad genes. CONCLUSIONS:
      These findings suggest that HtrA1 might positively regulate odontoblastic
      differentiation of hDPCs through activation of the TGF-beta1/Smad signaling
      pathway.

PMID- 29580723
TI  - The Performance of a Zirconium-based Root Filling Material with Artifact
      Reduction Properties in the Detection of Artificially Induced Root Fractures
      Using Cone-beam Computed Tomographic Imaging.
AB  - INTRODUCTION: Limited field of view cone-beam computed tomographic (CBCT) imaging
      has been used to augment clinical testing of vertical root fractures (VRFs);
      however, the presence of gutta-percha (GP) in the canal space generates
      substantial imaging artifacts that make fracture detection difficult. The purpose
      of this study was to evaluate the influence of a zirconium (Zr)-based root
      filling material with radiologic properties that reduce beam hardening (BH)
      artifacts using CBCT imaging in the in vitro diagnosis of VRFs. METHODS: One
      hundred seventy-six single-rooted mandibular premolar teeth were obtained, and
      half of these teeth were filled with GP or Zr (CPoint; EndoTechnologies, LLC,
      Shrewsbury, MA). VRFs were induced in 44 decoronated teeth in each group using an
      Instron (Norwood, MA) Universal Testing Machine. Each root was then placed in a
      dry human mandible and imaged with the Carestream 9000 3D CBCT system (Carestream
      Dental, Atlanta, GA). The images were evaluated by 6 oral maxillofacial
      radiologists (OMRs) and residents. RESULTS: The sensitivity was greater for
      detecting VRFs in the Zr group than the GP group (P = .035). However, the
      specificity was greater for the GP group than the Zr group (P = .028). Receiver
      operating characteristic area under the curve values were greater for the Zr
      group than the GP group, but these differences were not statistically
      significant. The OMRs outperformed the residents in the detection of VRFs in the
      Zr group with respect to specificity (P = .006) and positive predictive value (P
      = .012). CONCLUSIONS: The reduced BH of the Zr group improved the sensitivity of
      the detection of artificially induced VRFs. The ability to detect VRFs in the Zr
      group was further enhanced by clinical experience.

PMID- 29580724
TI  - Application of Enamel Matrix Derivative (Emdogain) in Endodontic Therapy: A
      Comprehensive Literature Review.
AB  - INTRODUCTION: Enamel matrix derivative (EMD) is a protein extract used for the
      treatment of periodontal defects and soft tissue recession. Its use in
      endodontics has been a subject of exploration, especially in regenerative
      procedures. The aim of this review was to evaluate the current literature
      available on the application of EMD in the field of endodontics. METHODS: An
      initial literature search of databases using different combinations of the search
      terms yielded 1089 articles. From the 29 qualified studies, there were 17 animal
      studies and 12 human case series and clinical trials. RESULTS: The evidence for
      the application of EMD as a direct pulp capping agent was relatively dichotomous.
      In determining the possible effect of EMD on pulpotomy procedures, only 1 animal
      study qualified under the criteria set forth previously. When comparing EMD
      against calcium hydroxide (Ca[OH]2), Portland cement, and mineral trioxide
      aggregate (MTA), Ca(OH)2 induced more histologic hard tissue formation, whereas
      MTA performed best clinically and radiographically. The scientific literature
      available is inconclusive on the effectiveness of EMD in preventing root
      resorption. In regeneration, EMD treatment induced mainly the formation of a
      cementumlike tissue at the apical region of the root's external surface and
      showed an ingrowth of newly formed hard tissues into the root canal space.
      CONCLUSIONS: The results of EMD application in endodontic treatments are highly
      variable, warranting additional research, specifically in the subjects of
      replantation and regeneration/revascularization.

PMID- 29580725
TI  - [Isolated sternal tuberculosis in immunocompetent adult].
AB  - Isolated sternal tuberculosis is a rarely described entity even in countries
      where tuberculosis is endemic. We report the case of 25 old years patient who
      presented with a chest wall mass. Imaging concluded to a (ring-enhancing
      hypodense soft tissue mass surrounding the sternum with sternal fracture).
      Malignancy was eliminated by a core needle biopsy. We noted clinical and
      radiological recovery with medical tuberculosis treatment. Neoplastic origin was
      removed by biopsy and anatomopathological study of the lesion.

PMID- 29580726
TI  - [White hemithorax in a young women carrying coffee and milk spots].
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF1) or Von Recklinghausen disease is an
      autosomal dominant genetic disorder with multivisceral manifestations. We report
      the case of a spontaneous haemothorax in a young lady wearing this genetic
      pathology. CASE REPORT: A 31-year-old woman with kyphoscoliosis developed acute
      chest pain and dyspnea. The physical examination revealed a right pleuritic
      syndrome, coffee and milk spots and neurofibromas of the trunk. Biological
      assessment showed anemia at 6.4g/dl. Chest x-ray revealed a right side
      opacification. The pleural puncture showed an incoagulable hemorrhagic fluid. The
      chest CT scan showed no vascular abnormalities. The diagnosis of spontaneous
      haemothorax, revealing NF1, was retained. Transfusion and thoracic drainage were
      performed followed by haemostasis surgery. Pleural exploration showed pleural
      hematoma with regard to the 5th intercostal space. Electrocoagulation and
      declogging were performed. The evolution of the patient was favorable.
      CONCLUSION: Haemothorax is a rare and serious complication which may reveal NF1.
      It must be suspected when sudden and spontaneous white haemithorax occurs in NF1.

PMID- 29580727
TI  - Folate receptor-directed orthogonal click-functionalization of siRNA
      lipopolyplexes for tumor cell killing in vivo.
AB  - The delivery of small interfering RNA (siRNA) and its therapeutic usage as an
      anti-cancer agent requires a carrier system for selective internalization into
      the cytosol of tumor cells. We prepared folate-bearing formulations by first
      complexing siRNA with the novel azido-functionalized sequence-defined
      cationizable lipo-oligomer 1106 (containing two cholanic acids attached to an
      oligoaminoamide backbone in T-shape configuration) into spherical, ~100-200 nm
      sized lipopolyplexes, followed by surface-functionalization with various folate
      conjugated DBCO-PEG agents. Both the lipo-oligomer and the different defined
      shielding and targeting agents with mono- and bis-DBCO and varying PEG length
      were generated by solid phase supported synthesis. A bivalent DBCO surface agent
      with a PEG24 spacer was identified as the optimal formulation in terms of
      nanoparticle size, folate receptor (FR) targeting, cellular uptake and gene
      silencing in vitro. Notably, near-infrared fluorescence bioimaging studies showed
      that double-click incorporation of bivalent DBCO-PEG24 resulted in
      siRNA/1106/DBCO2-ss2-PEG24-FolA lipopolyplexes with extended biodistribution and
      intratumoral delivery in a subcutaneous FR-positive leukemia mouse model.
      Intravenous administration of analogous therapeutic siRNA lipopolyplexes
      (directed against the kinesin spindle motor protein EG5) mediated tumoral EG5
      mRNA knockdown by ~60% and, in combination with the novel antitubulin drug
      pretubulysin, significantly prolonged survival of aggressive leukemia bearing
      mice without noticeable side effects.

PMID- 29580728
TI  - Effect of torrefaction pretreatment on the pyrolysis of rubber wood sawdust
      analyzed by Py-GC/MS.
AB  - The aim of this study was to investigate the effect of torrefaction on the
      pyrolysis of rubber wood sawdust (RWS) using pyrolysis-gas chromatography/mass
      spectrometry (Py-GC/MS). Three typical torrefaction temperatures (200, 250, and
      300  degrees C) and pyrolysis temperatures (450, 500, and 550  degrees C) were
      considered. The results suggested that only diethyl phthalate, belonging to
      esters, was detected at the torrefaction temperatures of 200 and 250  degrees C,
      revealing hemicellulose degradation. With the torrefaction temperature of 300 
      degrees C, esters, aldehydes, and phenols were detected, suggesting the
      predominant decomposition of hemicellulose and lignin. The double-shot pyrolysis
      indicated that the contents of oxy-compounds such as acids and aldehydes in
      pyrolysis bio-oil decreased with rising torrefaction temperature, implying that
      increasing torrefaction severity abated oxygen content in the bio-oil. With the
      torrefaction temperature of 300  degrees C, relatively more cellulose was
      retained in the biomass because the carbohydrate content in the pyrolysis bio-oil
      increased significantly.

PMID- 29580729
TI  - A review on microbial lipids as a potential biofuel.
AB  - Energy security, environmental concerns, and unstable oil prices have been the
      driving trifecta of demand for alternative fuels in the United States. The United
      States' dependence on energy resources, often from unstable oil-producing
      countries has created political insecurities and concerns. As we try to gain
      energy security, unconventional oil becomes more common, flooding the market, and
      causing the major downshift of the usual unstable oil prices. Meanwhile,
      consumption of fossil fuels and the consequent CO2 emissions have driven
      disruptions in the Earth's atmosphere and are recognized to be responsible for
      global climate change. While the significance of each of these three factors may
      fluctuate with global politics or new technologies, transportation energy will
      remain the prominent focus of multi-disciplined research. Bioenergy future
      depends on the price of oil. Current energy policy of the United States heavily
      favors petroleum industry. In this review, the current trend in microbial lipids
      as a potential biofuel is discussed.

PMID- 29580730
TI  - Risk factors for repeat surgical intervention in pediatric nephrolithiasis: A
      Pediatric Health Information System database study.
AB  - INTRODUCTION: Successful surgical therapy for pediatric upper urinary tract
      calculi (UUTC) minimizes the need for repeat surgical interventions. However,
      staged procedures, whether planned or unplanned, are sometimes necessary. We
      assessed predictors of repeat intervention for children with UUTC using a
      nationwide administrative dataset. METHODS: Using the Pediatric Health
      Information System (PHIS) dataset, we assessed children with UUTC undergoing
      shock wave lithotripsy (SWL) or ureteroscopy (URS) for an index stone from
      January 2010 to June 2015. Primary outcome was additional treatment for
      nephrolithiasis within 90 days. Patient and procedural variables were assessed as
      potential risks for retreatment. Multivariable logistic regression models were
      used to compare the risk of retreatment adjusting for potential confounding
      factors. RESULTS: A total of 2788 patients undergoing URS (2,216, 79.5%) and SWL
      (572, 20.5%) were identified. SWL, stenting at the index operation without pre
      index stenting, chronic comorbidities, renal calculi, and age <5 years were
      independent risk factors for retreatment. Use of ureteral stenting, most commonly
      employed in URS, was also a strong predictor of retreatment. Odds for
      reintervention, adjusted by multivariate modeling, are shown in the Figure.
      CONCLUSIONS: Adjusting for measured confounders, SWL is associated with a 2.6
      fold higher risk of repeat stone-related interventions. Additional patient
      related factors also increase likelihood of retreatment. Intra-operative stent
      placement is a strong predictor of retreatment, perhaps serving as a marker for
      complex cases or planned staged procedures. Prospective studies are needed to
      assess comparative effectiveness of SWL and URS and improve mono-therapeutic
      success for children with UUTC.

PMID- 29580731
TI  - Active surveillance for antenatally detected ureteroceles: Predictors of success.
AB  - INTRODUCTION: Historically, ureteroceles were surgically treated, as patients
      were diagnosed after developing symptoms. However, with the advance of fetal
      medicine, antenatal detection has provided an opportunity to look at the natural
      history of ureteroceles. OBJECTIVES: With data derived from a retrospective chart
      review of patients with ureteroceles that were detected antenatally, the current
      study aimed to determine which group of children would be at risk for failure on
      active surveillance. It was hypothesized that single system ureteroceles (SSU)
      and male patients with duplex system ureteroceles (DSU) would be ideal for
      observation. METHODS: Outcomes were assessed by descriptive statistics. Kaplan
      Meier curves were utilized to estimate median duration on active surveillance in
      both single and duplex cohorts. Breakthrough febrile urinary tract infection
      (fUTI) and surgery were determined by Cox regression in the duplex system cohort.
      Surgery was considered surveillance failure. RESULTS: A total of 102 patients (64
      females/38 males) met the criteria: 78 (76.5%) had DSU and 24 (23.5%) SSU. The
      overall median observation was 1.2 years (range 0.7-3.1). Follow-up ranged from
      0.3 to 11.7 years for SSU, and from 0.02 to 17.3 years for DSU. The predictors of
      failure of active surveillance (AS) in DSU (surgical intervention) were male
      gender (HR 1.8, 1.0-3.3, P = 0.037), or fUTI (HR 3.1, 1.7-5.8, P = 0.002).
      Predictors of fUTI were contralateral hydroureter or ipsilateral hydronephrosis
      +/- hydroureter (OR 9.5, 1.2-71.7, P = 0.028). Interestingly, vesicoureteral
      reflux (VUR) was not a predictor of fUTI. The SSU patients were ideal for AS,
      while in DSU, surveillance was successful in 30% of patients who were primarily
      females without contralateral hydroureter or ipsilateral hydronephrosis +/-
      hydroureter. However, in contradiction to the hypothesis, males were at higher
      risk for surgical intervention in the DSU cohort. CONCLUSION: Active surveillance
      is an option for patients with antenatally detected ureteroceles, but careful
      long term follow up is mandatory. Parents should be advised that surgical
      intervention may still be necessary, particularly in males with DSU.

PMID- 29580732
TI  - Non-stented versus stented urethroplasty for distal hypospadias repair: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Studies have shown that non-stented distal hypospadias repair
      eliminates stent-related bladder spasm and stent removal discomfort without
      increasing complications; however, results are inconsistent. We performed a
      systematic review to assess the complication rates of non-stented compared to the
      stented distal hypospadias repair. METHODS: The literature search included
      randomized control trials (RCTs) and cohort studies published prior to October
      2016 in all languages (PROSPERO CRD42016047563). All included studies were
      assessed according to Cochrane Collaborative recommendations and included for
      meta-analysis. Surgical outcomes from each treatment group were classified
      according to early complications and later final outcomes. Outcomes were
      expressed as relative risk (RR) and 95% confidence intervals (CI). Interstudy
      heterogeneity was assessed using chi-square and I2. Effect estimates were pooled
      using the inverse variant method with random effect model. Subgroup analysis was
      performed according to surgical technique (Mathieu versus tubularized incised
      plate) and study design. RESULTS: A total of 20 studies (14 cohorts, 6 RCTs) with
      2466 hypospadias repairs (1290 non-stented, 1176 stented) were included for the
      meta-analysis. Serious risk of bias was noted among the cohort studies with
      publication bias likely present, while the included RCTs were of moderate
      methodological quality. The overall pooled effect estimates comparing non-stented
      versus stented distal hypospadias repair showed no between-group difference for
      outcomes of early and late complications (RR 0.83, 95% CI 0.46-1.50; RR 0.96, 95%
      CI 0.92, 1.48; respectively) CONCLUSIONS: Current evidence of low to moderate
      quality suggests that there is likely no outcome difference between non-stented
      and stented distal hypospadias repair.

PMID- 29580733
TI  - The administration of adjuvant chemo(-immuno) therapy in the post ACOSOG-Z0011
      era; a population based study.
AB  - PURPOSE: The ACOSOG-Z0011-study has resulted in a trend to a more conservative
      treatment of the axilla for selected sentinel-node-positive patients. However,
      axillary nodal involvement has always been an important factor for tumor staging
      and tailoring adjuvant chemotherapy plans. This study evaluates the impact of
      omitting completion axillary lymph node dissection (cALND) on the administration
      of adjuvant chemo (-immuno)therapy in Dutch clinical T1-2N0M0 (cT1-2N0M0)
      sentinel-node-positive breast cancer patients. METHODS: Data were obtained from
      the nationwide NABON breast cancer audit. Descriptive analyses were used to
      demonstrate trends in axillary surgery and adjuvant chemo (-immuno)therapy.
      Multivariable logistic regression analyses were used to identify factors
      associated with the prescription of chemo (-immuno)therapy. RESULTS: In this
      cohort of 4331 patients, the omission of a cALND increased from 34% to 92%, and
      the administration of chemo (-immuno)therapy decreased from 68% to 55%, between
      2011 and 2015 (P < 0.001). Patients treated with cALND had an OR of 2.2 for
      receiving adjuvant chemo (-immuno)therapy compared with SLNB only patients. Lower
      age, a hormone receptor (HR) status other than HR-positive, HER2-negative,
      increasing tumor grade and stage, and a lymph node status >= pN2 were
      independently associated with a higher probability of chemo (-immuno)therapy (P <
      0.05). CONCLUSIONS: This study showed that Dutch cT1-2N0M0 sentinel node-positive
      breast cancer patients treated with cALND had a higher independent probability
      for receiving adjuvant chemo (-immuno)therapy compared with SLNB only patients,
      even when corrected for lymph node status and HR-status. Probably, the decisions
      to administer adjuvant chemo (-immuno)therapy were not only based on guidelines
      and tumor characteristics, but also on the preferences from physicians and
      patients.

PMID- 29580734
TI  - Morbidity of rectosigmoid resection in cytoreductive surgery for ovarian cancer.
      Risk factor analysis.
AB  - AIM: Rectosigmoid resection is often performed during cytoreductive surgery for
      ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the
      morbidity associated with rectosigmoid resection and the underlying risk factors.
      METHODS: We retrospectively assessed consecutive patients managed with
      rectosigmoid resection during cytoreductive surgery for ovarian cancer at our
      centre in Paris, France, between 2005 and 2013. All previously identified risk
      factors were analysed. Major complications were defined as grade III-IV in the
      Clavien-Dindo classification. RESULTS: Of 228 patients, 116 had primary and 112
      interval surgery; 43/228 [18.9%]; experienced major complications, and these were
      more common after primary surgery [24.1% vs. 13.4%, p = .04]. The 69 patients who
      had rectosigmoid resection [33 primary vs. 36 interval surgery, p = .32] had a
      higher morbidity rate compared to the other patients [30.4% vs. 14.6%, p = .006].
      The anastomotic leakage rate was 2.89%. By multivariate logistic regression,
      independent risk factors for morbidity were postmenopausal status [adjusted odds
      ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9], surgery after
      neoadjuvant chemotherapy [aOR, 4.4; 95%CI, 1.1;18.8], and peritoneal stripping of
      the left; paracolic gutter [aOR, 11.3; 95%CI, 2.3;54.3]. CONCLUSION: The
      morbidity of rectosigmoid resection during cytoreductive surgery for ovarian
      cancer seems acceptable. Ileostomy does not seem associated with a lower risk of
      major complications or adjuvant bevacizumab with a higher complication rate.

PMID- 29580735
TI  - The impact of primary tumour location in patients undergoing hepatic resection
      for colorectal liver metastasis.
AB  - BACKGROUND: Primary tumour location has long been debated as a prognostic factor
      in colorectal cancer patients with liver metastases (CRLM) undergoing liver
      resection. This retrospective study was conducted to clarify the prognostic value
      of tumour location after radical hepatectomy for CRLM and its underlying causes.
      METHODS: We retrospectively analysed clinical data from 420 patients with CRLM
      whom underwent liver resection between January 2002 and December 2015. Right
      sided (RS) tumours include tumours located in the cecum, ascending colon, and
      transverse colon, and left-sided (LS) tumours include those located in the
      splenic flexure, descending colon, sigmoid colon, and rectum. RESULTS: Both
      overall survival (OS) and disease-free survival (DFS) were similar between
      patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5
      year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was
      significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis
      showed that the RAS mutation on the LS and RS tumours have different prognostic
      impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P
      = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable
      analysis showed that RAS mutant is an independent factor influencing OS in
      patients with LS primary tumour only. CONCLUSIONS: The site of the primary tumour
      has no significant impact on the long-term survival in patients with CRLM
      undergoing radical surgery. However, prognostic value of RAS status differs
      depending on the site of the primary tumour.

PMID- 29580736
TI  - Quantitative phosphoproteomic analysis of caprine muscle with high and low meat
      quality.
AB  - During the conversion of muscle to meat, protein phosphorylation can regulate
      various biological processes that have important effects on meat quality. To
      investigate the phosphorylation pattern of protein on rigor mortis, goat
      longissimus thoracis and external intercostals were classified into two groups
      (high quality and low quality), and meat quality was evaluated according to meat
      quality attributes (Warner-Bratzler shear force, Color, pH and drip loss). A
      quantitative mass spectrometry-based phosphoproteomic study was conducted to
      analyze the caprine muscle at 12h postmortem applying the TiO2-SIMAC-HILIC (TiSH)
      phosphopeptide enrichment strategy. A total of 2125 phosphopeptides were
      identified from 750 phosphoproteins. Among them, 96 proteins had differed in
      phosphorylation levels. The majority of these proteins are involved in glucose
      metabolism and muscle contraction. The differential phosphorylation level of
      proteins (PFK, MYL2 and HSP27) in two groups may be the crucial factors of
      regulating muscle rigor mortis. This study provides a comprehensive view for the
      phosphorylation status of caprine muscle at rigor mortis, it also gives a better
      understanding of the regulation of protein phosphorylation on various biological
      processes that affect the final meat quality attributes.

PMID- 29580737
TI  - An approach for N-linked glycan identification from MS/MS spectra by target-decoy
      strategy.
AB  - Glycan structure determination serves as an essential step for the thorough
      investigation of the structure and function of protein. Currently, appropriate
      sample preparation followed by tandem mass spectrometry has emerged as the
      dominant technique for the characterization of glycans and glycopeptides.
      Although extensive efforts have been made to the development of computational
      approaches for the automated interpretation of glycopeptide spectra, the
      previously appeared methods lack a reasonable quality control strategy for the
      statistical validation of reported results. In this manuscript, we introduced a
      novel method that constructed a decoy glycan database based on the glycan
      structures in the target database, and searched the experimental spectra against
      both the target and decoy databases to find the best matched glycans.
      Specifically, a two-layer scoring scheme for calculating a normalized matching
      score is applied in the search procedure which enables the unbiased ranking of
      the matched glycans. Experimental analysis showed that our proposed method can
      report more structures with high confidence compared with previous approaches.

PMID- 29580738
TI  - SpliceVec: Distributed feature representations for splice junction prediction.
AB  - Identification of intron boundaries, called splice junctions, is an important
      part of delineating gene structure and functions. This also provides valuable
      insights into the role of alternative splicing in increasing functional diversity
      of genes. Identification of splice junctions through RNA-seq is by mapping short
      reads to the reference genome which is prone to errors due to random sequence
      matches. This encourages identification of splicing junctions through
      computational methods based on machine learning. Existing models are dependent on
      feature extraction and selection for capturing splicing signals lying in the
      vicinity of splice junctions. But such manually extracted features are not
      exhaustive. We introduce distributed feature representation, SpliceVec, to avoid
      explicit and biased feature extraction generally adopted for such tasks.
      SpliceVec is based on two widely used distributed representation models in
      natural language processing. Learned feature representation in form of SpliceVec
      is fed to multilayer perceptron for splice junction classification task. An
      intrinsic evaluation of SpliceVec indicates that it is able to group true and
      false sites distinctly. Our study on optimal context to be considered for feature
      extraction indicates inclusion of entire intronic sequence to be better than
      flanking upstream and downstream region around splice junctions. Further,
      SpliceVec is invariant to canonical and non-canonical splice junction detection.
      The proposed model is consistent in its performance even with reduced dataset and
      class-imbalanced dataset. SpliceVec is computationally efficient and can be
      trained with user-defined data as well.

PMID- 29580739
TI  - Clinical Implications of the BIM Deletion Polymorphism in Advanced Lung
      Adenocarcinoma Treated With Gefitinib.
AB  - BACKGROUND: Proapoptotic protein Bcl-2-like 11 (BIM) is a crucial tumor
      suppressor gene in lung cancer development. A 2903-bp genomic deletion
      polymorphism is present in BIM intron 2, which alters RNA splicing and impairs
      the generation of the death-inducing isoform of BIM and resistance to epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In the present
      study, we investigated the clinical implications of this genetic polymorphism in
      patients with advanced lung adenocarcinoma treated with gefitinib. MATERIALS AND
      METHODS: After genotyping the BIM deletion polymorphism in 111 patients with
      stage IIIB or IV lung adenocarcinoma receiving gefitinib, the hazard ratio (HR)
      and 95% confidence interval (CI) for progression-free survival and overall
      survival were estimated using Cox proportional hazards models. RESULTS:
      Possession of >= 1 deletion allele of the BIM polymorphism was observed in 18.02%
      of the patients. The BIM deletion polymorphism was an independent indicator of a
      shorter PFS (7.5 months vs. 11.3 months; HR, 2.38; 95% CI, 1.30-4.34; P = .005)
      and shorter OS (9.9 months vs. 27.5 months; HR, 2.53; 95% CI, 1.37-4.65; P =
      .003). Additionally, patients carrying the BIM deletion allele were more likely
      to experience acquired gefitinib-resistant disease. CONCLUSION: Our results
      indicate that the BIM deletion polymorphism might be a promising germline
      biomarker for gefitinib treatment in Chinese patients with lung adenocarcinoma.

PMID- 29580740
TI  - Negative voice-content as a full mediator of a relation between childhood
      adversity and distress ensuing from hearing voices.
AB  - A key predictor of whether or not an individual who hears voices (auditory verbal
      hallucinations; AVH) meets criteria for a psychiatric diagnosis is the level of
      negative content of the voices (e.g., threats, criticism, abuse). Yet the factors
      that contribute to negative voice-content are still not well understood. This
      study aimed to test the hypotheses that levels of childhood adversity would
      predict levels of negative voice-content, and that negative voice-content would
      partially mediate a relation between childhood adversity and voice-related
      distress. These hypotheses were tested in a clinical sample of 61 patients with
      formally diagnosed psychotic disorders (48 schizophrenia, 13 bipolar). We found
      evidence consistent with negative voice-content fully (not partially) mediating
      the relation between childhood adversity and voice-related distress. Although
      bivariate analyses found depression to be associated with both negative voice
      content and voice-related distress, we found no evidence of an indirect effect of
      childhood adversity on either negative voice-content or voice-related distress
      via depression. Alternative study designs are now needed to test if our findings
      are replicable and causal. Should they be, it will be necessary for psychological
      therapies to devise ways to reduce negative voice-content itself, rather than
      just changing beliefs about voices. A number of techniques are discussed (Avatar
      Therapy, Compassion Focused Therapy, voice-dialogue) that already show promise
      for this.

PMID- 29580741
TI  - Accidental deaths among persons with schizophrenia: A nationwide population-based
      cohort study.
AB  - OBJECTIVES: Persons with schizophrenia have a shorter life expectancy by 15
      20years compared to the background population, but little is known about deaths
      caused by accidents. We aimed to investigate the rates of accidental death among
      persons with schizophrenia and compare these rates with those of the background
      population. METHODS: We conducted a national register-based cohort study of all
      persons born in Denmark between 1955 and 2011. The cohort included 2,703,307
      persons, representing 56,845,085 person years at risk. We compared rates of
      accidental death between persons with schizophrenia and those without by using
      Cox regression analysis. The main outcome measure was hazard ratio (HR) for
      accidental death. RESULTS: A total of 12,425 accidental deaths were identified,
      including 371 accidental deaths among persons with schizophrenia. We found an
      increased HR for both women with schizophrenia (10.47; 95% CI=8.07-13.58) and men
      with schizophrenia (8.33; 95% CI=7.44-9.33) compared to the background
      population. After adjusting for substance abuse, we found attenuated HRs for both
      women (HR=3.22; 95% CI=2.46-4.20) and men (HR=3.23; 95% CI=2.87-3.63).
      CONCLUSIONS: Schizophrenia is a strong independent risk factor for accidental
      deaths. Substance abuse seems to constitute a substantial part of the
      association.

PMID- 29580742
TI  - Propionibacterium Acnes Persists Despite Various Skin Preparation Techniques.
AB  - PURPOSE: To investigate the efficacy of various skin preparations at eradicating
      Propionibacterium acnes in the dermal layer of the skin. METHODS: Twelve healthy
      volunteers consented to participate in this study. Each subject's upper back was
      prepped using 4 different techniques: an isopropyl alcohol control, chlorhexidine
      gluconate paint, chlorhexidine gluconate plus a mechanical scrub, and a high
      concentration chlorhexidine gluconate plus a mechanical scrub. A 3-mm dermal
      punch biopsy specimen was obtained at each preparation site. The 4 punch biopsy
      specimens were cultured for 14 days to assess for P. acnes growth. A Fisher's
      exact test was used to compare the proportion of positive cultures in each group
      and across biopsy sites. A Skillings-Mack test was used to compare the degree of
      culture positivity between the treatment arms. RESULTS: There were no reported
      complications in any of our subjects. P. acnes grew in 7 of the 12 control sites,
      5 of the 12 chlorhexidine gluconate sites, 6 of the 12 chlorhexidine plus
      mechanical scrub sites, and 6 of the 12 high-concentration chlorhexidine
      gluconate plus mechanical scrub sites. There were no statistically significant
      differences between any of the treatment arms (P = .820). CONCLUSIONS: P. acnes
      persisted despite a variety of clinically relevant skin antisepsis preparations
      and techniques. LEVEL OF EVIDENCE: Level II, prospective comparative study.

PMID- 29580743
TI  - Surgical Trends in Arthroscopic Hip Surgery Using a Large National Database.
AB  - PURPOSE: To assess the practice trends in hip arthroscopy, including
      femoroplasty, acetabuloplasty, and labral repair Current Procedure Terminology,
      4th edition (CPT-4), codes that have been implemented since many of the previous
      studies were published, without concerns for Hawthorne or observer effect as can
      be seen during a board collection window, and in a larger volume of patients with
      a more comprehensive database than previous published data. METHODS: The
      MarketScan Commercial Claims and Encounters database was searched using CPT-4
      codes to identify patients who underwent any arthroscopic hip procedure from 2008
      to 2013. Patients identified were characterized by gender, age group, and year of
      the initial procedure. Regression analysis was used to evaluate differences in
      surgical trends between individual patient groups delineated by age and gender.
      The Cochran-Armitage trend test was used to identify significant differences in
      surgical trends seen yearly. RESULTS: A total of 62,782 arthroscopic hip
      procedures in 31,569 surgeries in 27,997 patients were identified and included
      from 2008 through 2013. The number of surgeries in the database increased every
      year. After changes to CPT coding in 2011, femoroplasty became the most common
      procedure in 2012, comprising 28% of all procedures performed in 2013. Patients
      ages 40 to 49 underwent the most procedures (7,467, 27%). Females were more
      likely to undergo any arthroscopic procedure during the study period (.068% vs
      .041%, P < .0001). A total of 2,754 patients (10%) underwent a second surgery
      during the study period. A total of 1,625 patients (6%) underwent a total hip
      arthroplasty following an arthroscopic procedure during the study period.
      CONCLUSIONS: Arthroscopic hip procedures continue to increase, with femoroplasty,
      labral repair, and acetabuloplasty being the 3 most common procedures performed.
      Females are more likely to undergo any procedure, and labral repair is now
      performed more commonly than labral debridement. LEVEL OF EVIDENCE: Level IV,
      cross-sectional study.

PMID- 29580744
TI  - Anthropometric Study of the Radiocapitellar Joint.
AB  - PURPOSE: There is scant knowledge about the relationship between the size of the
      radial head and the size of the capitellum. Also, no data exist comparing the
      size of the capitellum between the left and the right elbow. METHODS: Eight pairs
      of elbows and 12 single elbows from fresh-frozen cadavers were obtained for this
      study. The vertical height and anterior width of the capitellum were measured
      with digital calipers. Four different measurements were performed at the radial
      head: longest outer diameter, shortest outer diameter, the long dish diameter,
      and short dish diameter. The Pearson intrarater intraclass correlation
      coefficients were obtained for all measurements. RESULTS: For the paired elbows,
      the correlations ranged between 0.95 and 0.96 for the capitellar dimensions and
      0.77 and 0.98 for the radial head dimensions. The correlations between the long
      outer diameter of the radial head with the vertical height and the anterior width
      of the capitellum were 0.8 and 0.9, respectively. CONCLUSIONS: There is a high
      correlation between the long outer diameter of the radial head and the vertical
      height of the capitellum as well its anterior width. There is also a high
      correlation between the left and the right elbow. CLINICAL RELEVANCE: These
      findings are relevant to radiocapitellar arthroplasty and may be useful for
      radiocapitellar prosthetic design as well as in the preoperative planning of
      cases in which the radial head and/or the capitellum is destroyed.

PMID- 29580745
TI  - Biomechanical characterization of three iliac screw fixation techniques: A finite
      element study.
AB  - We aim to characterize the biomechanical properties of a modified iliac screw
      fixation method compared with the classic iliac screw fixation and the S2 alar
      iliac screw (S2AI) fixation using a FEM. A three-dimensional, non-linear FEM of
      lumbosacral spine and pelvis (L1-pelvis) was modified to simulate 3 different
      iliac screw fixations based on posterior screw fusion. The peak von Mises stress
      (PVMS) values of the iliac screws in the 3 different iliac screw fixations were
      recorded in during flexion/extension/axial rotation/lateral bending. The
      interaction stress which arose between the screw head and the shaft of iliac
      screws, was also measured for each case. The PVMS values of the 3 different iliac
      screw fixation techniques were lower than the fatigue strength levels under
      physiological loadings. PVMS of iliac screws was observed in the screw shaft for
      S2AI, in the screw neck for the modified iliac screw technique, and in the offset
      connectors of the classic iliac screw technique. The interaction between the
      screw head and the neck was compressed in modified iliac screw fixation
      technique. On the other hand, distraction force was observed in the S2AI
      technique between the screw head and the screw shaft. This FEM study supports our
      previous clinical results, which found that the modified iliac screw fixation
      technique can be an effective alternative sacropelvic fixation technique
      comparable to the classic iliac screw and the S2AI technique.

PMID- 29580746
TI  - REVEAL risk score in patients with chronic thromboembolic pulmonary hypertension
      receiving riociguat.
AB  - BACKGROUND: The REVEAL risk score (RRS) was developed to predict survival in
      patients with pulmonary arterial hypertension (PAH), based on multiple patient
      characteristics. Herein we calculated RRS for patients in the randomized CHEST-1
      study and open-label CHEST-2 extension study of riociguat in inoperable or
      persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). We
      investigated the effect of riociguat vs placebo on RRS in the CHEST-1 study, and
      the relationship between RRS and long-term outcomes in the CHEST-2 study.
      METHODS: RRS was calculated post hoc for baseline and Week 16 of CHEST-1 and Week
      12 of CHEST-2, based on 9 evaluable elements. Patients were grouped into risk
      strata by RRS. Relationships between RRS and both survival and clinical worsening
      free survival were examined by Kaplan-Meier and Cox proportional hazards
      analyses. RESULTS: Overall, 237 patients completed CHEST-1 and entered CHEST-2.
      In CHEST-1, riociguat significantly improved RRS (p < 0.0001) and risk stratum (p
      < 0.001) vs placebo from baseline to Week 16. RRS at baseline, and at Week 16,
      and change in RRS during CHEST-1 were significantly associated with survival
      (hazard ratios for a 1-point reduction in RRS: 0.702, 0.692, and 0.682,
      respectively) and clinical worsening-free survival (hazard ratios: 0.697, 0.719,
      and 0.754, respectively) over 2 years in CHEST-2. CONCLUSIONS: Riociguat improved
      RRS in patients with inoperable and persistent/recurrent CTEPH. RRS at baseline
      and Week 16, and change in RRS from baseline, predicted survival and clinical
      worsening-free survival. This analysis of RRS in patients with inoperable or
      persistent/recurrent CTEPH suggests utility for the RRS in indications beyond
      PAH.

PMID- 29580747
TI  - MR imaging features of peritoneal alveolar echinococcosis.

PMID- 29580748
TI  - Letter to the Editor referring to the retracted publication entitled "Straticyte
      demonstrates prognostic value over oral epithelial dysplasia grade for oral
      potentially malignant lesion assessment" by Hwang et al.

PMID- 29580749
TI  - Novel Biomarkers in Cardiac Resynchronization Therapy: Hepatocyte Growth Factor
      Is an Independent Predictor of Clinical Outcome.
AB  - INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is
      beneficial for selected heart failure (HF) patients, although nonresponse to
      therapy is still prevalent. We investigated a set of novel biomarkers associated
      with various pathophysiological pathways of HF. Our purpose was to assess their
      ability to predict clinical outcomes after CRT. METHODS: We studied 136 chronic
      HF patients undergoing CRT. We measured the plasma levels of fractalkine,
      pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix
      metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the
      study was 5-year all-cause mortality, and we considered the absence of 6-month
      reverse remodelling (defined as at least a 15% decrease in end-systolic volume)
      as a secondary endpoint. RESULTS: Fifty-eight patients died during the 5-year
      follow-up period and 66 patients were categorized as nonresponders. In
      multivariable models, only an increased HGF was an independent predictor of both
      mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase)
      and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1
      standard deviation increase). Applying HGF to the basic multivariable model of
      both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P<.0001;
      integrated discrimination improvement=0.06; 95%CI, 0.02-0.11) and reverse
      remodelling (net reclassification improvement=0.39; 95%CI, 0.07-0.71; P=.01;
      integrated discrimination improvement=0.03; 95%CI, 0.00-0.06) resulted in a
      statistically significant reclassification and discrimination improvement.
      CONCLUSIONS: Of the investigated biomarkers, only HGF predicted clinical outcomes
      following CRT independently of other parameters. Reclassification analyses showed
      that HGF measurements could be useful in refining patient selection.

PMID- 29580751
TI  - Novel 1,3,4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2
      mediated JAK2/STAT3 signals as evidenced through data-based mathematical
      modeling.
AB  - We attempted a preclinical study using DMH-induced CRC rat model to evaluate the
      antitumor potential of our recently synthesized 1,3,4-thiadiazoles. The molecular
      insights were confirmed through ELISA, qRT-PCR and western blot analyses. The CRC
      condition was produced in response to COX-2 and IL-6 induced activation of
      JAK2/STAT3 which, in turn, was due to the enhanced phosphorylation of JAK2 and
      STAT3. The treatment with 1,3,4-thiadiazole derivatives (VR24 and VR27) caused
      the significant blockade of this signaling pathway. The behavior of STAT3
      populations in response to IL-6 and COX-2 stimulations was further confirmed
      through data-based mathematical modeling using the quantitative western blot
      data. Finally, VR24 and VR27 restored the perturbed metabolites associated to DMH
      induced CRC as evidenced through 1H NMR based serum metabolomics. The tumor
      protecting ability of VR24 and VR27 was found comparable or to some degree better
      than the marketed chemotherapeutics, 5-flurouracil.

PMID- 29580750
TI  - Targeted next-generation-sequencing for reliable detection of targetable
      rearrangements in lung adenocarcinoma-a single center retrospective study.
AB  - Oncogenic rearrangements leading to targetable gene fusions are well-established
      cancer driver events in lung adenocarcinoma. Accurate and reliable detection of
      these gene fusions is crucial to select the appropriate targeted therapy for each
      patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay
      (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk
      immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged,
      18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and
      specificity of 100% for detection of ALK rearrangements using the OFA panel. In
      addition, targeted next generation sequencing allowed us to analyze a set of 23
      driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR
      ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All
      EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted
      next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit,
      Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed
      by Alk immunohistochemistry and all but one by ALK FISH. In our experience,
      targeted next-generation sequencing is a reliable and timesaving tool for
      multiplexed detection of targetable rearrangements. Therefore, targeted next
      generation sequencing represents an efficient alternative to time-consuming
      single target assays currently used in molecular pathology.

PMID- 29580752
TI  - Dose-dependent effects of frutalin on in vitro maturation and fertilization of
      pig oocytes.
AB  - The aim of the present study was to evaluate the effect of frutalin (FTL) on in
      vitro maturation (IVM), and fertilization (IVF) of pig oocytes. In the Experiment
      1, cumulus-oocyte complexes (COCs) were submitted to IVM in maturation medium
      alone or supplemented with different FTL concentration (0.6, 6 and 60 MUg/mL), or
      0.3 MUg/mL doxorubicin (DXR). After IVM, some oocytes were evaluated for
      chromatin configuration, and the remaining oocytes were submitted to in vitro
      fertilization. In Experiment 2, matured oocytes were fertilized in IVF medium
      alone (control) or in presence of different FTL concentration (0.6, 6 and 60
      MUg/mL), or 0.3 MUg/mL DXR. After 18 h post fertilization, the endpoints
      penetration rate, monospermy, spermatozoa per oocyte, and the IVF efficiency were
      evaluated in both experiments. In Experiment 1, 6 and 60 MUg/mL FTL, as well as
      DXR increased (P < 0.05) the rate of oocytes with abnormal chromatin
      configuration when compared to oocyte matured in control medium alone or
      supplemented with 0.6 MUg/mL FTL. The percentage of meiotic resumption in oocytes
      cultured with 60 MUg/mL FTL or DXR was less (P < 0.05) than in the other
      treatments. Moreover, oocytes matured with 6 or 60 MUg/mL FTL and DXR had a
      lesser IVM efficiency when compared to those matured with 0.6 MUg/mL FTL or in
      control medium. Additionally, there was a greater (P < 0.05) with culture in a
      medium containing 6 MUg/mL FTL for the rate of partenogenetically activated
      oocytes when compared with the other treatments. Culturing of COCs during IVM in
      a medium containing 6 or 60 FTL resulted in a lesser (P < 0.05) sperm penetration
      and spermatozoa/oocyte rates when compared to other treatments, and IVF
      efficiency was less (P < 0.05) than that in control medium alone or with a medium
      containing 0.6 MUg/mL FTL. In Experiment 2, culturing in a medium containing 0.6
      MUg/mL FTL resulted in greater (P < 0.05) monospermy and IVF efficiency rates
      when compared to culturing in the control medium. In addition, culturing in a
      medium with 6 and 60 MUg/mL FTL resulted in a lesser (P < 0.05) spermatozoa
      penetration, sperm/oocyte rates and IVF efficiency, although there were greater
      (P < 0.05) monospermy rates. In conclusion, culturing in a medium containing 0.6
      MUg/mL FTL resulted in lesser spermatozoa penetration rates and number of
      spermatozoa/oocyte increasing the IVF efficiency without harmful effects. Use of
      a greater concentration of FTL in the medium has toxic effects during oocyte
      maturation and results in a reduced IVF efficiency.

PMID- 29580753
TI  - Sephadex filtration as successful alternative to density-gradient centrifugation
      procedures for ram sperm selection with improved kinetics.
AB  - Density-gradients centrifugation (DGC) and filtration columns (FC) are used to
      separate deformed or dead sperm, debris, and other cells that may negatively
      affect the fertilizing capacity of sperm in fresh, chilled and frozen/thawed
      semen. The present study was conducted to evaluate the suitability of DGC
      (BoviPure(r), Percoll(r) and Accudenz(r)) and FC (Sephadex G-15(r)) sperm
      selection procedures for fresh-extended and cold-stored ram semen by assessment
      of post-treatment sperm quality variables. Twenty normospermic ejaculates from
      ten adult Merino rams were used. Sperm concentration of recovered cells was
      greater (P < 0.001) after BoviPure treatment than other procedures in both fresh
      and cold semen. With the Sephadex method, there were more desirable values than
      with use of DGC procedures in several sperm motility variables measured by using
      the CASA system. In non-refrigerated semen samples, the percentage of progressive
      sperm motility (%PSM) after Sephadex filtration was greater (P < 0.05) than after
      BoviPure treatment; the straightline velocity (VSL) value after Sephadex
      filtration was greater (P < 0.01) than after Accudenz treatment; the amplitude of
      lateral head displacement (ALH) after Sephadex and Accudenz treatment was less
      than non-filtered semen (P < 0.001) and after Percoll (P < 0.01) and BoviPure (P
      < 0.05) treatments. In cold-stored semen samples, the %PSM after Sephadex
      filtration was greater than non-filtered (P < 0.05) semen and after BoviPure (P <
      0.05), Percoll (P < 0.05) and Accudenz (P < 0.001) treatments. It is concluded
      that Sephadex column filtration can be used to select ram sperm in non
      refrigerated and cooled semen, because percentage progressively motile sperm and
      some other sperm motility characteristics are greater with use of this techniques
      as compared with use of DGC methods.

PMID- 29580754
TI  - Energy utilization associated with regular activity breaks and continuous
      physical activity: A randomized crossover trial.
AB  - AIMS: To quantify and compare energy utilization associated with prolonged
      sitting alone, or interrupted with regular activity breaks and/or an additional
      bout of continuous physical activity. METHODS AND RESULTS: Thirty six adults (11
      males, BMI 24.1 +/- 4.6) completed four interventions: (1) prolonged sitting
      (SIT), (2) sitting with 2-min of walking every 30 min (RAB), (3) prolonged
      sitting with 30-min of continuous walking at the end of the day (SIT + PA), (4) a
      combination of the activities in (2) and (3) above (RAB + PA). All walking was at
      a speed and incline corresponding to 60% VO2max. Energy utilization over 7 h for
      each intervention was estimated using indirect calorimetry. Compared to SIT, SIT
      + PA increased total energy utilization by 709 kJ (95% CI 485-933 kJ), RAB by 863
      kJ (95% CI 638-1088 kJ), and RAB + PA by 1752 kJ (95% CI 1527-1927 kJ) (all p <
      0.001). There was no difference in total energy utilization between SIT + PA and
      RAB, however, post-physical activity energy utilization in RAB was 632 kJ greater
      than SIT + PA (95% CI 561-704 kJ; p < 0.001). CONCLUSIONS: Short frequent
      activity, results in greater accumulation of elevated post-physical activity
      energy utilization compared to a single bout of continuous activity; however the
      total energy utilization is similar. Combining activity breaks with a longer
      continuous bout of activity will further enhance energy utilization, and in the
      longer term, may positively affect weight management of a greater magnitude than
      either activity pattern performed alone. TRIAL REGISTRATION:
      ANZCTR12614000624684.

PMID- 29580755
TI  - Incidence and clinical outcomes of the different neovascular forms of age-related
      macular degeneration in Valencia (Spain).
AB  - OBJECTIVE: To analyse the incidence and outcomes of the different neovascular
      subtypes in age-related macular degeneration (AMD). MATERIAL AND METHODS: A
      retrospective review was carried out on patients with neovascular AMD treated in
      the University and Polytechnic Hospital la Fe in Valencia by the same retinal
      physician (RGP) between December 2012 and July 2015. The anatomic classification
      of the neovascular lesions was recorded, as well as the number of intravitreal
      treatments administered and the change in visual acuity (VA) obtained throughout
      the follow-up. RESULTS: A total number of 174 eyes of 156 patients (mean age:
      79.9years) with a minimum follow-up of 4 months were included. The anatomic
      classification of choroidal neovascularisation (CNV) showed the presence of type1
      lesions in 40,8%, type2 lesions in 12%, type3 lesions in 31%, and mixed lesions
      in 14.4%, with 1.7% showing polypoidal choroidal vasculopathy features. Overall,
      the mean baseline VA was 0,32, improving to 0,38 at 24months, after having
      received a mean of 9.3 injections. Type2, 3, and mixed forms showed a visual
      result significantly lower than type1, but there was no significant difference in
      the polypoidal vasculopathy. CONCLUSIONS: Type 1 CNV was the most common finding,
      and was associated with a better visual prognosis, compared to the other
      neovascular lesions.

PMID- 29580756
TI  - Case series of ocular involvement due to dengue. First reported cases in
      Guatemala.
AB  - OBJECTIVE: Describe the ocular findings of a case series of 8 patients with a
      diagnosis of dengue. MATERIALS AND METHODS: Review of clinical records and
      interviews with patients during outpatient visits, after informed consent was
      obtained and following the ethical standards of the Helsinki declaration. The
      patients were diagnosed with diagnosis by IgM / IgG dengue serology in whom
      ocular involvement was identified, between January and October 2017 in Retinal
      vascular clinic of the "Dr. Rodolfo Robles Valverde Hospital", Guatemala.
      RESULTS: The 8 patients, 5 men and 3 women from rural areas in Guatemala, were
      diagnosed with dengue by IgM / IgG serology with associated ocular involvement.
      The mean age was 32.3 years, with the oldest being 45 years old and the youngest
      being 20 years old. The ocular manifestations identified were, 4 neuroretinitis,
      3 venous obstructions, 3 maculopathies, 2 serous detachments, 1 episcleritis, and
      1 vasculitis. Two patients developed optic atrophy after resolving the
      neuroretinitis, and 1 developed peri-foveal scarring after the maculopathy. The
      ocular involvement was resolved in all patients after treatment, with an
      improvement in visual acuity, although in some cases damage to the visual field
      developed as a sequela of neuroretinitis. CONCLUSION: It is necessary to consider
      dengue as an important differential diagnosis in an endemic country such as
      Guatemala. There are a large number of ocular manifestations due to direct
      involvement, as well as by an immune system reaction, and thus avoid considering
      the different ocular manifestations as idiopathic, or due to a different
      condition.

PMID- 29580757
TI  - External ophthalmomyiasis due to Dermatobia hominis. A case report.
AB  - CLINICAL CASE: A 46-year-old woman with no relevant medical history, native of
      Honduras and resident in Spain for one and a half months. The patient went to the
      Emergency Department due to inflammation of the upper eyelid of the right eye,
      with an area that simulated an abscess. This was drained (obtaining hardly any
      purulent content). Treatment was prescribed with oral and topical antibiotics, as
      well as an anti-inflammatory drug. One week later the patient returned, with
      improvement of the inflammatory signs, but with discomfort and corneal erosions.
      After eversion of the upper eyelid, a "worm" type parasite emerged from the
      tarsus. The extraction was completed with a clamp, and was later identified as
      Dermatobia hominis (Dh) by examination of a fresh specimen. The subsequent
      outcome of the patient was favourable. DISCUSSION: Preseptal cellulitis in
      patients from tropical and sub-tropical areas can be caused by Dh.

PMID- 29580758
TI  - Nitric oxide-donating compounds for IOP lowering in glaucoma.
AB  - INTRODUCTION: An elevated intraocular pressure (IOP) remains the main risk factor
      for progression of glaucoma upon which we can efficiently act. Pharmacological
      strategies to reduce IOP are directed towards the reduction of aqueous humour
      (AH) production and/or the increase in AH drainage through the uveoscleral
      pathway. However, there are no drugs currently available as first-line treatment
      to increase AH outflow primarily via the conventional route. Ocular nitric oxide
      (NO) production takes place in AH outflow pathways and in the ciliary muscle,
      modulating the cellular response to elevated IOP. METHODS: This review describes
      the mechanism of action of endogenous NO and NO-donating compounds that are under
      research. It includes information regarding pre-clinical and clinical studies
      previously conducted with these compounds, discussing their role and therapeutic
      potential in the pharmacological treatment of ocular hypertension in glaucoma.
      RESULTS: The topical ocular administration of NO-donating compounds significantly
      lowered IOP and maintained it in animal models of glaucoma and subjects with
      ocular hypertension. CONCLUSIONS: The mechanism of action of these compounds is
      novel and scientific evidence that shows promising results. However, there is a
      need for more comprehensive studies to assess long-term safety and tolerability
      in order to properly evaluate their use in chronic therapies.

PMID- 29580759
TI  - Uveitis and serous retinal detachment secondary to systemic dabrafenib and
      trametinib.
AB  - CASE REPORT: The case is presented of a 39-year-old woman with metastatic
      melanoma treated with dabrafenib and trametinib. She presented with a severe
      acute panuveitis with granulomatous anterior uveitis, vitritis, and multiple
      serous retinal detachments. Dabrafenib and trametinib were suspended, and
      treatment with a systemic and topical corticosteroid was started. A good response
      was obtained, with a recovery of visual acuity of 1.0 in both eyes within two
      weeks. DISCUSSION: Dabrafenib and trametinib can lead to severe uveitis.
      Treatment with corticosteroids and discontinuation of therapy with dabrafenib and
      trametinib led to an anatomical and functional improvement, and resolved the
      episode rapidly. Ophthalmologists must be aware of this toxicity, given the
      increasing use of those drugs.

PMID- 29580760
TI  - Iris metastasis as a first manifestation of lung adenocarcinoma.
AB  - OBJECTIVE: To describe a case of lung adenocarcinoma for which the first clinical
      manifestation was an iris metastasis. CASE REPORT: A 76-year-old male patient
      came for consultation referring a "pinkish speck" on his right eye. On
      biomicroscopy examination, a mass was found on the iris of the right eye.
      Subsequent systemic work-up of the patient revealed a left lung adenocarcinoma.
      DISCUSSION: Although uncommon, iris metastasis secondary to lung cancer should be
      part of differential diagnosis in iris tumours.

PMID- 29580761
TI  - The impact of social protection and poverty elimination on global tuberculosis
      incidence: a statistical modelling analysis of Sustainable Development Goal 1.
AB  - BACKGROUND: The End TB Strategy and the Sustainable Development Goals (SDGs) are
      intimately linked by their common targets and approaches. SDG 1 aims to end
      extreme poverty and expand social protection coverage by 2030. Achievement of SDG
      1 is likely to affect the tuberculosis epidemic through a range of pathways. We
      estimate the reduction in global tuberculosis incidence that could be obtained by
      reaching SDG 1. METHODS: We developed a conceptual framework linking key
      indicators of SDG 1 progress to tuberculosis incidence via well described risk
      factor pathways and populated it with data from the SDG data repository and the
      WHO tuberculosis database for 192 countries. Correlations and mediation analyses
      informed the strength of the association between the SDG 1 subtargets and
      tuberculosis incidence, resulting in a simplified framework for modelling. The
      simplified framework linked key indicators for SDG 1 directly to tuberculosis
      incidence. We applied an exponential decay model based on linear associations
      between SDG 1 indicators and tuberculosis incidence to estimate tuberculosis
      incidence in 2035. FINDINGS: Ending extreme poverty resulted in a reduction in
      global incidence of tuberculosis of 33.4% (95% credible interval 15.5-44.5) by
      2035 and expanding social protection coverage resulted in a reduction in
      incidence of 76.1% (45.2-89.9) by 2035; both pathways together resulted in a
      reduction in incidence of 84.3% (54.7-94.9). INTERPRETATION: Full achievement of
      SDG 1 could have a substantial effect on the global burden of tuberculosis. Cross
      sectoral approaches that promote poverty reduction and social protection
      expansion will be crucial complements to health interventions, accelerating
      progress towards the End TB targets. FUNDING: World Health Organization.

PMID- 29580762
TI  - Predicting the effect of improved socioeconomic health determinants on the
      tuberculosis epidemic.

PMID- 29580763
TI  - The upcoming UN general assembly resolution on tuberculosis must also benefit
      children.

PMID- 29580764
TI  - Histology of the mesorectal lymphatics explains aspects of rectal cancer.

PMID- 29580765
TI  - Preoperative erythropoietin treatment improves survival following major hepatic
      resection in a cirrhotic rat model.
AB  - AIM: Major hepatic resection of a cirrhotic liver may result in a fatal clinical
      course. Preoperative erythropoietin (EPO) treatment has been shown to have
      protective properties and to stimulate liver regeneration. This study aims to
      investigate the effect of preoperative EPO on survival following major hepatic
      resection in a cirrhotic rat model. METHODS: Cirrhotic liver was induced by
      intraperitoneal injection of thioacetamide (200mg/kg/mL) in 72 Lewis rats. Each
      36 rats received EPO (1IU/g, every second day, 5 times preoperatively) or saline
      (control) and major hepatectomy (removal of the left and half of the median lobe)
      was performed. Biochemical and immunohistochemical parameters, cytokines and
      overall survival were compared following surgery. RESULTS: Rats that received
      preoperative EPO had decreased hepatic aspartate aminotransferase, alanine
      aminotransferase and interleukin (IL)-1beta expression, 48hours following
      surgery. They had increased hepatocyte growth factor and vascular endothelial
      growth factor expression at 1hour, increased IL-6 expression at 24, 48 and
      120hours and increased Ki-67, 120hours following surgery. Overall, survival was
      significantly improved among EPO-treated rats (P=0.034). CONCLUSION: Preoperative
      EPO treatment has a protective effect and stimulates liver regeneration, leading
      to improved overall survival following major hepatectomy in a cirrhotic rat
      model.

PMID- 29580766
TI  - Editor-in-Chief's Comment on the Paleo-oncology Special Issue.

PMID- 29580767
TI  - Fatty liver index is associated to pulse wave velocity in healthy subjects: Data
      from the Brisighella Heart Study.
AB  - BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is associated to increased
      risk of cardiovascular disease. Our aim was to evaluate association of indexes of
      fatty liver with arterial stiffness (AS). METHODS: We analyzed data of adult
      volunteers visited during the last Brisighella survey. We evaluated the Pulse
      Wave Velocity (PWV) and the following non-invasive indexes of liver steatosis:
      Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), Hepatic Steatosis
      Index (HSI). We compared patients according to the risk of Non-Alcoholic
      Steatohepatitis (NASH): low-risk (BMI < 28 and no diabetes), intermediate-risk
      (BMI >= 28 or diabetes), high-risk (BMI >= 28 and diabetes). Multiple Linear
      Regression analysis was assessed for predictors of AS. RESULTS: We studied 1731
      volunteers. In subjects with low metabolic risk, HSI (RR = 0.138, 95%CI 0.105
      0.170, p < 0.001), FLI (RR = 0.024, 95%CI 0.016-0.032, p < 0.001), LAP (RR =
      0.014, 95%CI 0.008-0.020, p < 0.001) and Serum Uric Acid (RR = 0.150, 95%CI 0.024
      0.275, p = 0.019) were significant predictors of AS. HSI and FLI emerged as
      predictors of PWV in intermediate risk group (RR = 0.116, 95%CI 0.071-0.160, p <
      0.001; RR = 0.010, 95%CI 0.001-0.020, p = 0.041). In volunteers with high risk,
      FLI and Uric Acid were related to PWV (RR = 0.049, 95%CI 0.011-0.087, p = 0.013;
      RR = 0.632, 95% CI 0.222-1.041, p = 0.003). CONCLUSION: Fatty liver indirect
      indexes were associated to AS in subjects with different metabolic risk profiles.

PMID- 29580768
TI  - Functional Connectivity Between Anterior Insula and Key Nodes of Frontoparietal
      Executive Control and Salience Networks Distinguish Bipolar Depression From
      Unipolar Depression and Healthy Control Subjects.
AB  - BACKGROUND: Patients with bipolar depression are characterized by dysregulation
      across the full spectrum of mood, differentiating them from patients with
      unipolar depression. The ability to switch neural resources among the default
      mode network, salience network, and executive control network (ECN) has been
      proposed as a key mechanism for adaptive mood regulation. The anterior insula is
      implicated in the modulation of functional network switching. Differential
      connectivity between anterior insula and functional networks may provide insights
      into pathophysiological differences between bipolar and unipolar mood disorders,
      with implications for diagnosis and treatment. METHODS: Resting-state functional
      magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24
      bipolar, and 39 healthy control subjects). Pearson correlations were computed
      between bilateral insula seed regions and a priori defined target regions from
      the default mode network, salience network, and ECN. After r-to-z transformation,
      a one-way multivariate analysis of covariance was conducted to identify
      significant differences in connectivity between groups. Post hoc pairwise
      comparisons were conducted and Bonferroni corrections were applied. Receiver
      operating characteristics were computed to assess diagnostic sensitivity.
      RESULTS: Patients with bipolar depression evidenced significantly altered right
      anterior insula functional connectivity with the inferior parietal lobule of the
      ECN relative to patients with unipolar depression and control subjects. Right
      anterior insula-inferior parietal lobule connectivity significantly discriminated
      patients with bipolar depression. CONCLUSIONS: Impaired functional connectivity
      between the anterior insula and the inferior parietal lobule of the ECN
      distinguishes patients with bipolar depression from those with unipolar
      depression and healthy control subjects. This finding highlights a
      pathophysiological mechanism with potential as a therapeutic target and a
      clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and
      specificity.

PMID- 29580769
TI  - Novel DYW-type pentatricopeptide repeat (PPR) protein BLX controls mitochondrial
      RNA editing and splicing essential for early seed development of Arabidopsis.
AB  - In plants, RNA editing is a post-transcriptional process that changes specific
      cytidine to uridine in both mitochondria and plastids. Most pentatricopeptide
      repeat (PPR) proteins are involved in organelle RNA editing by recognizing
      specific RNA sequences. We here report the functional characterization of a PPR
      protein from the DYW subclass, Baili Xi (BLX), which contains five PPR motifs and
      a DYW domain. BLX is essential for early seed development, as plants lacking the
      BLX gene was embryo lethal and the endosperm failed to initiate cellularization.
      BLX was highly expressed in the embryo and endosperm, and the BLX protein was
      specifically localized in mitochondria, which is essential for BLX function. We
      found that BLX was required for the efficient editing of 36 editing sites in
      mitochondria. Moreover, BLX was involved in the splicing regulation of the fourth
      intron of nad1 and the first intron of nad2. The loss of BLX function impaired
      the mitochondrial function and increased the reactive oxygen species (ROS) level.
      Genetic complementation with truncated variants of BLX revealed that, in addition
      to the DYW domain, only the fifth PPR motif was essential for BLX function. The
      upstream sequences of the BLX-targeted editing sites are not conserved,
      suggesting that BLX serves as a novel and major mitochondrial editing factor
      (MEF) via a new non-RNA-interacting manner. This finding provides new insights
      into how a DYW-type PPR protein with fewer PPR motifs regulates RNA editing in
      plants.

PMID- 29580770
TI  - A new empiricism for harm reduction.
AB  - This commentary reflects on the key methodological innovations presented in
      Nicole Vitellone's recent book Social Science of the Syringe (Vitellone, 2017).
      Vitellone's book offers a critical account of harm reduction steeped in the
      material practices of empirical inquiry. In Vitellone's hands, harm reduction
      becomes a "matter of care"; a means of thinking, feeling and knowing the life
      worlds of people who inject drugs, such that these worlds may be encountered
      differently. Vitellone couches this analysis in terms of a novel social science
      of the syringe. Throughout her analysis, Vitellone asks us to reimagine the
      syringe, not as a fixed technical object, but as a dense point of capacities and
      affects around which certain forms of sociality become possible. The book follows
      the implications of this logic for scholars interested in the social and
      political contexts - the situated materialities - of injection drug use. I will
      close with some brief reflections on Vitellone's book in relation to broader
      efforts to advance a novel social science for harm reduction.

PMID- 29580771
TI  - Interactions of amyloid-beta peptides on lipid bilayer studied by single molecule
      imaging and tracking.
AB  - The amyloid-beta peptides (Abeta40 and Abeta42) feature prominently in the
      synaptic dysfunction and neuronal loss associated with Alzheimer's disease (AD).
      This has been proposed to be due either to interactions between Abeta and cell
      surface receptors affecting cell signaling, or to the formation of calcium
      permeable channels in the membrane that disrupt calcium homeostasis. In both
      mechanisms the cell membrane is the primary cellular structure with which Abeta
      interacts. Abeta concentrations in human bodily fluids are very low (pM-nM)
      rendering studies of the size, composition, cellular binding sites and mechanism
      of action of the oligomers formed in vivo very challenging. Most studies,
      therefore, have utilized Abeta oligomers prepared at micromolar peptide
      concentrations, where Abeta forms oligomeric species which possess easily
      observable cell toxicity. Such toxicity has not been observed when nM
      concentrations of peptide are used in the experiment highlighting the importance
      of employing physiologically relevant peptide concentrations for the results to
      be of biological significance. In this paper single-molecule microscopy was used
      to monitor Abeta oligomer formation and diffusion on a supported lipid bilayer at
      nanomolar peptide concentrations. Abeta monomers, the dominant species in
      solution, tightly associate with the membrane and are highly mobile whereas
      trimers and higher-order oligomers are largely immobile. Abeta dimers exist in a
      mixture of mobile and immobile states. Oligomer growth on the membrane is more
      rapid for Abeta40 than for the more amyloidogenic Abeta42 but is largely
      inhibited for a 1:1 Abeta40:Abeta42 mixture. The mechanism underlying these
      Abeta40-Abeta42 interactions may feature in Alzheimer's pathology.

PMID- 29580773
TI  - Patient-centeredness and endometriosis: Definition, measurement, and current
      status.
AB  - The patient-centeredness of care is important for health care quality, especially
      because it was recently associated with health-related quality of life, which is
      increasingly being recognized as the ultimate outcome parameter of health care.
      Therefore, insight into the definition, measurement, and current status of the
      patient-centeredness of clinics is important for all health care professionals
      caring for patients with endometriosis. The definition of patient-centered
      endometriosis care is based on research into the most common preferences, needs,
      and values of patients with endometriosis and can be summarized in ten
      dimensions. One valid and reliable questionnaire exists, the ENDOCARE
      questionnaire, which allows measuring the patient-centeredness status of an
      endometriosis clinic. This questionnaire has been used to benchmark centers in
      different countries and has allowed the identification of ten targets for
      improving the patient-centeredness of endometriosis care. The next step would be
      to use the ENDOCARE questionnaire before and after an improvement project.

PMID- 29580774
TI  - Comment on Favorable association of polyphenol-rich diets with lung function:
      Cross-sectional findings from the Moli-sani study.

PMID- 29580772
TI  - Acute Brain Dysfunction: Development and Validation of a Daily Prediction Model.
AB  - BACKGROUND: The goal of this study was to develop and validate a dynamic risk
      model to predict daily changes in acute brain dysfunction (ie, delirium and
      coma), discharge, and mortality in ICU patients. METHODS: Using data from a
      multicenter prospective ICU cohort, a daily acute brain dysfunction-prediction
      model (ABD-pm) was developed by using multinomial logistic regression that
      estimated 15 transition probabilities (from one of three brain function states
      [normal, delirious, or comatose] to one of five possible outcomes [normal,
      delirious, comatose, ICU discharge, or died]) using baseline and daily risk
      factors. Model discrimination was assessed by using predictive characteristics
      such as negative predictive value (NPV). Calibration was assessed by plotting
      empirical vs model-estimated probabilities. Internal validation was performed by
      using a bootstrap procedure. RESULTS: Data were analyzed from 810 patients (6,711
      daily transitions). The ABD-pm included individual risk factors: mental status,
      age, preexisting cognitive impairment, baseline and daily severity of illness,
      and daily administration of sedatives. The model yielded very high NPVs for "next
      day" delirium (NPV: 0.823), coma (NPV: 0.892), normal cognitive state (NPV:
      0.875), ICU discharge (NPV: 0.905), and mortality (NPV: 0.981). The model
      demonstrated outstanding calibration when predicting the total number of patients
      expected to be in any given state across predicted risk. CONCLUSIONS: We
      developed and internally validated a dynamic risk model that predicts the daily
      risk for one of three cognitive states, ICU discharge, or mortality. The ABD-pm
      may be useful for predicting the proportion of patients for each outcome state
      across entire ICU populations to guide quality, safety, and care delivery
      activities.

PMID- 29580775
TI  - Reply.

PMID- 29580776
TI  - Successful Resection of Esophageal Carcinoma With a Double Aortic Arch.
AB  - We report a patient with esophageal carcinoma accompanied by a double aortic
      arch. The preoperative computed tomography scan only detected the right aortic
      arch, but we found the double aortic arch during the operation. The patient
      underwent an esophagectomy through a left thoracotomy. Preoperative three
      dimensional reconstruction of computed tomography images should be conducted to
      completely understand the anomalies of the great vessels.

PMID- 29580777
TI  - Quality of Life After Cardiac Operations Based on the Minimal Clinically
      Important Difference Concept.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is an increasingly important
      issue in assessing the consequences of any surgical or medical intervention. Our
      study aimed to evaluate change in HRQOL 6 months after elective cardiac
      operations and to identify specific predictors of poor HRQOL. METHODS: In this
      prospective, single-center study, HRQOL was evaluated before and 6 months after
      the operation using the Medical Outcome Study 36-Item Short Form Health Survey
      questionnaire and its two components: the Physical Component Summary and the
      Mental Component Summary. We distinguished patients with worsening of HRQOL
      according to the minimal clinically important difference. All consecutive adult
      patients undergoing cardiac operations were included. RESULTS: The preoperative
      and postoperative 36-Item Short Form Health Survey questionnaires were completed
      by 326 patients, and 24 patients died before completing follow-up questionnaires.
      On the basis of the definition used, clinically significant deterioration of
      HRQOL was observed in 93 patients (26.6%) for the Physical Component Summary and
      in 99 patients (28.2%) for the Mental Component Summary. Renal replacement for
      acute renal failure and mechanical ventilation for longer than 48 hours were
      independent risk factors for Physical Component Summary and Mental Component
      Summary worsening or death. CONCLUSIONS: Although our study showed overall
      improvement of quality of life after cardiac operations, more than one-quarter of
      the patients manifested deterioration of HRQOL at 6 months postoperatively. The
      findings from this study should help clinicians to inform patients about their
      likely postoperative functional status and quality of life.

PMID- 29580778
TI  - Two-Field Lymphadenectomy During Esophagectomy: The Presence of Thoracic Duct
      Lymph Nodes.
AB  - BACKGROUND: Resection of the thoracic duct is part of the formal en bloc
      mediastinal esophagolymphadenectomy for cancer, although with the adaptation of
      minimally invasive techniques, some centers started to leave the thoracic duct
      compartment in situ. However, previous studies reported thoracic duct lymph nodes
      in this compartment that may contain metastasis. The aim of this study was to
      assess the presence and number of lymph nodes in the fatty tissue surrounding the
      thoracic duct. METHODS: A right-sided thoracoscopic esophagectomy was performed
      on seven fresh-frozen human cadavers (male, n = 3; female, n = 4). The esophagus
      and lymph node stations 7, 8, and 9 were resected en bloc, followed by resection
      of the thoracic duct compartment consisting of the fatty tissue covering the
      aorta, the thoracic duct and thoracic duct lymph nodes. Lymph nodes were
      visualized by a hematoxylin and eosin stain and counted macroscopically and
      microscopically. RESULTS: Thoracic duct lymph nodes were found in 6 of 7 cadavers
      (86%), with a median number of 1 (range, 0 to 6). Nodes were predominantly
      located in the area of the azygos vein. A median of 4 subcarinal nodes (range, 1
      to 8) and 2 periesophageal nodes (range, 1 to 4) were present. CONCLUSIONS: This
      study shows that thoracic duct lymph nodes are located within the fatty tissue
      surrounding the thoracic duct. Resection of this compartment during an
      esophagectomy for cancer increases lymph node yield.

PMID- 29580779
TI  - Long-Term Results for Clinical Stage IA Lung Cancer: Comparing Lobectomy and
      Sublobar Resection.
AB  - BACKGROUND: Lobectomy has been compared with sublobar resection for the treatment
      of stage IA non-small cell lung cancer (NSCLC). Accurate long-term data are
      lacking on the risk of recurrence in routine clinical practice. This study used a
      unique and representative dataset to compare recurrence, overall survival (OS),
      and lymph node staging between lobectomy and sublobar resection. METHODS: The
      American College of Surgeons performed a Special Study of the National Cancer
      Data Base, by reabstracting records to augment NSCLC data with enhanced
      information on preoperative comorbidity and cancer recurrence from 2007 to 2012.
      For patients treated with lobectomy or sublobar resection (wedge resection or
      segmentectomy) for clinical stage IA NSCLC, propensity matching and competing
      risks models compared 5-year OS and risk of cancer recurrence. Secondary measures
      included lymph nodes collected, pathologic upstaging, and surgical margin status.
      RESULTS: A total of 1,687 patients with stage IA NSCLC were identified (1,354 who
      underwent lobectomy, and 333 who had sublobar resections). Propensity matching
      yielded 325 pairs. Lobectomy and sublobar resection groups had similar 5-year OS
      (61.8% vs 55.6%, p = 0.561). The sublobar group had a 39% increased risk of NSCLC
      recurrence (hazard ratio, 1.39; 95% confidence interval, 1.04 to 1.87). Median
      lymph node counts were higher for lobectomy-treated patients (7 [3, 10] vs 1 [0,
      4], p < 0.001)]. CONCLUSIONS: In an enhanced national dataset representative of
      outcomes for stage IA NSCLC, sublobar resection was associated with a 39%
      increased risk of cancer recurrence. The majority of patients treated with
      sublobar resection had an inadequate lymph node assessment. These real-world
      results must be considered when existing clinical trial results comparing these
      treatments are extrapolated for clinical use.

PMID- 29580780
TI  - Cardiac Calcified Amorphous Tumor in a Newborn.
AB  - Calcified amorphous tumors (CATs) of the heart are rare, nonneoplastic,
      intracavitary lesions, previously thought of as pseudotumors, hamartomas, or
      calcified thrombi, only reported in few adults in the available literature. This
      report describes a case of a pedunculated oscillating CAT arising from the left
      atrial appendage that prolapses through the mitral valve and causes severe mitral
      regurgitation in a newborn. This is the only case of cardiac CAT described in a
      neonate.

PMID- 29580781
TI  - Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory
      Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial
      Cystitis/Bladder Pain Syndrome Patients.
AB  - OBJECTIVE: To investigate whether urinary levels of macrophage migration
      inhibitory factor (MIF) are elevated in interstitial cystitis/bladder pain
      syndrome (IC/BPS) patients with Hunner lesions and also whether urine MIF is
      elevated in other forms of inflammatory cystitis. METHODS: Urine samples were
      assayed for MIF by enzyme-linked immunosorbent assay. Urine samples from 3 female
      groups were examined: IC/BPS patients without (N = 55) and with Hunner lesions (N
      = 43), and non-IC/BPS patients (N = 100; control group; no history of IC/BPS;
      cancer or recent bacterial cystitis). Urine samples from 3 male groups were
      examined: patients with bacterial cystitis (N = 50), radiation cystitis (N = 18)
      and noncystitis patients (N = 119; control group; negative for bacterial
      cystitis). RESULTS: Urine MIF (mean MIF pg/mL +/-  standard error of the mean)
      was increased in female IC/BPS patients with Hunner lesions (2159 +/- 435.3)
      compared with IC/BPS patients without Hunner lesions (460 +/- 114.5) or non
      IC/BPS patients (414 +/- 47.6). Receiver operating curve analyses showed that
      urine MIF levels discriminated between the 2 IC groups (area under the curve =
      72%; confidence interval 61%-82%). Male patients with bacterial and radiation
      cystitis had elevated urine MIF levels (2839 +/- 757.1 and 4404 +/- 1548.1,
      respectively) compared with noncystitis patients (681 +/- 75.2). CONCLUSION:
      Urine MIF is elevated in IC/BPS patients with Hunner lesions and also in patients
      with other bladder inflammatory and painful conditions. MIF may also serve as a
      noninvasive biomarker to select IC/BPS patients more accurately for endoscopic
      evaluation and possible anti-inflammatory treatment.

PMID- 29580782
TI  - Physiological differences between female limited, alternative life history
      strategies: The Alba phenotype in the butterfly Colias croceus.
AB  - Across a wide range of taxa, individuals within populations exhibit alternative
      life history strategies (ALHS) where their phenotypes dramatically differ due to
      divergent investments in growth, reproduction and survivorship, with the
      resulting trade-offs directly impacting Darwinian fitness. Though the maintenance
      of ALHS within populations is fairly well understood, little is known regarding
      the physiological mechanisms that underlie ALHS and how environmental conditions
      can affect the evolution and expression of these phenotypes. One such ALHS, known
      as Alba, exists within females of many species in the butterfly genus Colias.
      Previous works in New World species not only found that female morphs differ in
      their wing color due to a reallocation of resources away from the synthesis of
      wing pigments to other areas of development, but also that temperature played an
      important role in these trade-offs. Here we build on previous work conducted in
      New World species by measuring life history traits and conducting lipidomics on
      individuals reared at hot and cold temperatures in the Old World species Colias
      croceus. Results suggest that the fitness of Alba and orange morphs likely varies
      with rearing temperature, where Alba females have higher fitness in cold
      conditions and orange in warm. Additionally shared traits between Old and New
      World species suggest the Alba mechanism is likely conserved across the genus.
      Finally, in the cold treatment we observe an intermediate yellow morph that may
      have decreased fitness due to slower larval development. This cost may manifest
      as disruptive selection in the field, thereby favoring the maintenance of the two
      discrete morphs. Taken together these results add insights into the evolution of,
      and the selection on, the Alba ALHS.

PMID- 29580783
TI  - Enhancement of fermentative hydrogen production from Spirogyra sp. by increased
      carbohydrate accumulation and selection of the biomass pretreatment under a
      biorefinery model.
AB  - In this work, hydrogen (H2) was produced through the fermentation of Spirogyra
      sp. biomass by Clostridium butyricum DSM 10702. Macronutrient stress was applied
      to increase the carbohydrate content in Spirogyra, and a 36% (w/w) accumulation
      of carbohydrates was reached by nitrogen depletion. The use of wet microalga as
      fermentable substrate was compared with physically and chemically treated biomass
      for increased carbohydrate solubilisation. The combination of drying, bead
      beating and mild acid hydrolysis produced a saccharification yield of 90.3%
      (w/w). The H2 production from Spirogyra hydrolysate was 3.9 L H2 L-1, equivalent
      to 146.3 mL H2 g-1 microalga dry weight. The presence of protein (23.2 +/- 0.3%
      w/w) and valuable pigments, such as astaxanthin (38.8% of the total pigment
      content), makes this microalga suitable to be used simultaneously in both food
      and feed applications. In a Spirogyra based biorefinery, the potential energy
      production and food-grade protein and pigments revenue per cubic meter of
      microalga culture per year was estimated on 7.4 MJ, US $412 and US $15,
      respectively, thereby contributing to the cost efficiency and sustainability of
      the whole bioconversion process.

PMID- 29580784
TI  - Predictive modelling of chromium removal using multiple linear and nonlinear
      regression with special emphasis on operating parameters of bioelectrochemical
      reactor.
AB  - Bioelectrochemical system (BES) is a novel, self-sustaining metal removal
      technology functioning on the utilization of chemical energy of organic matter
      with the help of microorganisms. Experimental trials of two chambered BES reactor
      were conducted with varying substrate concentration using sodium acetate (500
      mg/L to 2000 mg/L COD) and different initial chromium concentration (Cri) (10-100
      mg/L) at different cathode pH (pH 1-7). In the current study mathematical models
      based on multiple linear regression (MLR) and non-linear regression (NLR)
      approach were developed using laboratory experimental data for determining
      chromium removal efficiency (CRE) in the cathode chamber of BES. Substrate
      concentration, rate of substrate consumption, Cri, pH, temperature and hydraulic
      retention time (HRT) were the operating process parameters of the reactor
      considered for development of the proposed models. MLR showed a better
      correlation coefficient (0.972) as compared to NLR (0.952). Validation of the
      models using t-test analysis revealed unbiasedness of both the models, with t
      critical value (2.04) greater than t-calculated values for MLR (-0.708) and NLR (
      0.86). The root-mean-square error (RMSE) for MLR and NLR were 5.06 % and 7.45 %,
      respectively. Comparison between both models suggested MLR to be best suited
      model for predicting the chromium removal behavior using the BES technology to
      specify a set of operating conditions for BES. Modelling the behavior of CRE will
      be helpful for scale up of BES technology at industrial level.

PMID- 29580785
TI  - Donor mesenchymal stem cell linetics after transamniotic stem cell therapy
      (TRASCET) for experimental spina bifida.
AB  - PURPOSE: We sought to examine donor mesenchymal stem cell (MSC) kinetics after
      transamniotic stem cell therapy (TRASCET) in experimental spina bifida. METHODS:
      Pregnant Sprague-Dawley dams exposed to retinoic acid for the induction of fetal
      neural tube defects received volume-matched intra-amniotic injections on
      gestational day 17 (E17; term=E22): either amniotic fluid MSCs (afMSCs) labeled
      with a luciferase reporter gene (n=78), or luciferase protein alone (n=66).
      Samples from twelve organ systems from each surviving fetus with spina bifida
      (total n=60) were screened via microplate luminometry at term. RESULTS: Donor
      afMSCs were identified exclusively in the placenta, umbilical cord, spleen, bone
      marrow, hip bones, defect, and brain. Luminometry was negative in control fetuses
      receiving luciferase alone (p<0.001). Signal intensity in relative light units
      (RLUs) was moderately correlated between the defect and the hip bones (rho=0.38,
      p=0.048), and between the placenta and the brain (rho=0.40, p=0.038).
      CONCLUSIONS: Amniotic mesenchymal stem cells engraft to specific sites after
      concentrated intra-amniotic injection in the setting of spina bifida. A
      hematogenous route encompassing the bone marrow as well as distant central
      nervous system homing are fundamental constituents of cell trafficking. These
      findings must be considered during eventual patient selection for transamniotic
      stem cell therapy in the prenatal management of spina bifida.

PMID- 29580786
TI  - Neurodevelopmental outcomes in CDH survivors: A single institution's experience.
AB  - PURPOSE: Survivors of congenital diaphragmatic hernia (CDH) face high morbidity.
      We studied the neurodevelopmental outcomes of CDH survivors at a single
      institution. METHODS: CDH survivors born July 2006-March 2016 at a free-standing
      children's hospital were reviewed. Neurodevelopment was assessed using the
      Peabody Developmental Motor Scales (PDMS-2) broken into gross, fine, and total
      motor quotients. Data collected included prenatal variables (liver herniation,
      defect laterality, observed:expected total fetal lung volume (o:eTFLV) on MRI),
      birth demographics (sex, race, estimated gestational age (EGA), birth weight
      (BtWt), 5 min APGAR, associated anomalies), and therapies/hospital course
      (HFOV/HFJV, ECMO, timing of repair, pulmonary hypertension (PHTN) severity,
      length of stay, ventilator days). Variables were analyzed using mixed linear
      modeling. RESULTS: Sixty-eight children were included. Most patients had left
      sided CDH (55/68, 81%) without liver herniation (42/68, 62%). ECMO utilization
      was 25/68 (37%). The mean [95% confidence interval] gross motor quotient for the
      entire cohort was 87 [84-91], fine motor quotient was 92 [88-96], and total motor
      quotient was 88 [84-93], representing below average, average, and below average
      functioning, respectively. o:eTFLV predicted fine motor quotient among prenatal
      variables. Associated anomalies and ECMO use predicted all quotients in the final
      model. CONCLUSIONS: Associated anomalies and ECMO use predict neurodevelopmental
      delay in CDH survivors. TYPE OF STUDY: Retrospective observational study;
      Prognostic. LEVEL OF EVIDENCE: II.

PMID- 29580787
TI  - Using bibliometrics to analyze the state of academic productivity in US pediatric
      surgery training programs.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME)
      Common Program Requirements state that faculty must establish and maintain an
      environment of inquiry and scholarship. Bibliometrics, the statistical analysis
      of written publications, assesses scientific productivity and impact. The goal of
      this study was to understand the state of scholarship at Pediatric Surgery
      training programs. METHODS: Following IRB approval, Scopus was used to generate
      bibliometric profiles for US Pediatric Surgery training programs and faculty.
      Statistical analyses were performed. RESULTS: Information was obtained for 430
      surgeons (105 female) from 48 US training programs. The mean lifetime h
      index/surgeon for programs was 14.4 +/- 4.7 (6 programs above 1 SD, 9 programs
      below 1 SD). The mean 5-yearh-index/surgeon for programs was 3.92 +/- 1.5 (7
      programs above 1 SD, 8 programs below 1 SD). Programs accredited after 2000 had a
      lower lifetime h-index than those accredited before 2000 (p=0.0378). Female
      surgeons had a lower lifetime h-index (p<0.0001), 5-yearh-index (p=0.0049), and m
      quotient (p<0.0001) compared to males. Mean lifetime h-index increased with
      academic rank (p<0.0001), with no gender differences beyond the assistant
      professor rank (p=NS). CONCLUSION: Variability was identified based on
      institution, gender, and rank. This information can be used for benchmarking the
      academic productivity of faculty and programs and as an adjunct in
      promotion/tenure decisions. TYPE OF STUDY: Original Research. LEVEL OF EVIDENCE:
      n/a.

PMID- 29580788
TI  - Tailoring CT Dose to Patient Size: Implementation of the Updated 2017 ACR Size
      specific Diagnostic Reference Levels.
AB  - RATIONALE AND OBJECTIVES: To use an automatic computed tomography (CT) dose
      monitoring system to analyze the institutional chest and abdominopelvic CT dose
      data as regards the updated 2017 American College of Radiology (ACR) diagnostic
      reference levels (DRLs) based on water-equivalent diameter (Dw) and size-specific
      dose estimates (SSDE) to detect patient-size subgroups in which CT dose can be
      optimized. MATERIALS AND METHODS: All chest CT examinations performed between
      July 2016 and April 2017 with and without contrast material, CT of the pulmonary
      arteries, and abdominopelvic CT with and without contrast material were included
      in this retrospective study. Dw and SSDE were automatically calculated for all
      scans using a previously validated in-house developed Matlab software and stored
      into our CT dose monitoring system. CT dose data were analyzed as regards the
      updated ACR DRLs (size groups: 21-25 cm, 25-29 cm, 29-33 cm, 33-37 cm, 37-41 cm).
      SSDE and volumetric computed tomography dose index (CTDIvol) were used as CT dose
      parameter. RESULTS: Overall, 30,002 CT examinations were performed in the study
      period, 3860 of which were included in the analysis (mean age 62.1 +/- 16.4
      years, Dw 29.0 +/- 3.3 cm; n = 577 chest CT without contrast material, n = 628
      chest CT with contrast material, n = 346 CT of chest pulmonary, n = 563
      abdominopelvic CT without contrast material, n = 1746 abdominopelvic CT with
      contrast material). Mean SSDE and CTDIvol relative to the updated DRLs were 43.3
      +/- 26.4 and 45.1 +/- 27.9% for noncontrast chest CT, 52.3 +/- 23.1 and 52.0 +/-
      23.1% for contrast-enhanced chest CT, 68.8 +/- 29.5 and 70.0 +/- 31.0% for CT of
      pulmonary arteries, 41.9 +/- 29.2 and 43.3 +/- 31.3% for noncontrast
      abdominopelvic CT, and 56.8 +/- 22.2 and 58.8 +/- 24.4% for contrast-enhanced
      abdominopelvic CT. Lowest dose compared to the DRLs was found for the Dw group of
      21-25 cm in noncontrast abdominopelvic CT (SSDE 30.4 +/- 21.8%, CTDIvol 30.8 +/-
      21.4%). Solely the group of patients with a Dw of 37-41 cm undergoing noncontrast
      abdominopelvic CT exceeded the ACR DRL (SSDE 100.3 +/- 59.0%, CTDIvol 107.1 +/-
      63.5%). CONCLUSIONS: On average, mean SSDE and CTDIvol of our institutional chest
      and abdominopelvic CT protocols were lower than the updated 2017 ACR DRLs. Size
      specific subgroup analysis revealed a wide variability of SSDE and CTDIvol across
      CT protocols and patient size groups with a transgression of DRLs in noncontrast
      abdominopelvic CT of large patients (Dw 37-41 cm).

PMID- 29580789
TI  - Designing a Curriculum for Professionalism and Ethics Within Radiology:
      Identifying Challenges and Expectations.
AB  - Although professionalism and ethics represent required competencies, they are
      more challenging than other competencies to design a curriculum for and teach.
      Reasons include variability in agreed definitions of professionalism within
      medicine and radiology. This competency is also framed differently whether as
      roles, duties, actions, skills, behavior, beliefs, and attitudes. Standardizing a
      curriculum in professionalism is difficult because each learner's (medical
      student/resident) professional experiences and interactions will be unique.
      Professionalism is intertwined throughout all (sub) specialties and areas and its
      teaching cannot occur in isolation as a standalone curriculum. In the past,
      professionalism was not emphasized enough or at all, with global (or no)
      assessments, with the potential effect of trainees not valuing it. Although we
      can teach it formally in the classroom and informally in small groups, much of
      professionalism is witnessed and learned as "hidden curricula". The formal,
      informal, and hidden curricula often contradict each other creating confusion,
      disillusion, and cynicism in trainees. The corporatization of medicine
      pressurizes us to increase efficiency (throughput) with less focus on aspects of
      professionalism that add value, creating a disjoint between what we do in
      practice and preach to trainees. Progressively, expectations for our curriculum
      include providing evidence for the impacts of our efforts on patient outcomes.
      Generational differences in the perception of professionalism and the
      increasingly diverse and multicultural society in which we live affects our
      interpretation of professionalism, which can add to confusion and
      misunderstanding. The objectives of this article are to outline challenges facing
      curriculum design in professionalism and to make suggestions to help educators
      avoid or overcome them.

PMID- 29580790
TI  - Recognition of Neonatal Lymphatic Flow Disorder: Fetal MR Findings and Postnatal
      MR Lymphangiogram Correlation.
AB  - RATIONALE AND OBJECTIVES: This study aimed to describe prenatal and postnatal
      imaging features and outcomes of neonates with neonatal lymphatic disorders
      (NLDs). MATERIALS AND METHODS: An institutional review board-approved search of
      the radiology database for patients with NLD identified five patients. Inclusion
      criteria include prenatal imaging (fetal magnetic resonance [MR] imaging and
      ultrasound) and postnatal three-dimensional T2 Sampling Perfection with
      Application optimized Contrasts using different flip angle Evolution (SPACE) and
      dynamic contrast-enhanced MR lymphangiography within 6 months of life. Chart
      review was undertaken to evaluate morbidity and mortality. RESULTS: Prenatal
      finding of "nutmeg lung" or fetal pulmonary lymphatic disorder was identified in
      all five patients on fetal MR imaging, and in four of five patients on fetal
      ultrasound. Postnatal dynamic contrast-enhanced MR lymphangiography demonstrated
      abnormal lymphatic flow to the lungs in four of five patients, but absent in the
      single patient with coexisting hypoplastic left heart syndrome (HLHS). Dermal
      backflow was seen in one patient, also the only patient with prenatal body wall
      edema. Three patients with lymphatic flow to the lungs only were classified as
      neonatal chylothorax. The patient with dermal backflow and perfusion to the lungs
      was diagnosed with central lymphatic flow disorder (CLFD). The HLHS patient with
      normal lymphatic perfusion maintained the HLHS diagnosis. Of the five patients,
      the patient with CLFD and the one with HLHS expired because of respiratory
      distress. CONCLUSIONS: NLDs can be recognized on prenatal and postnatal imaging
      and may be primary, as in neonatal chylothorax or CLFD, or secondary. In this
      small series, "nutmeg lung" was present in all patients. Prenatal imaging
      demonstrates that body wall edema may correlate with postnatal dermal backflow,
      which, in our small cohort, carried a poor prognosis.

PMID- 29580791
TI  - Breast Lesions Detected via Molecular Breast Imaging: Physiological Parameters
      Affecting Interpretation.
AB  - RATIONALE AND OBJECTIVES: To evaluate correlations between molecular breast
      imaging (MBI) descriptor characteristics and positive predictive value (PPV) in
      detecting breast cancer. MATERIALS AND METHODS: A retrospective review was
      performed on 193 suspicious findings from 153 women (31-81 years) with positive
      MBI examinations. We assessed associations between (i) lesion pattern (mass vs.
      nonmass) and PPV; (ii) lesion pattern and suspected likelihood of cancer (low vs.
      moderate vs. high); (iii) background parenchymal uptake (BPU) (homogeneous vs.
      heterogeneous) and PPV; (iv) breast density (dense vs. non-dense) and PPV; and
      (v) BPU and density. RESULTS: One hundred ten of 153 patients were diagnosed with
      malignancy or high-risk pathology (PPV1 = 71.9%), and 130/193 biopsies resulted
      in malignant or high-risk lesions (PPV3 = 67.4%). Biopsies of mass vs. nonmass
      findings had comparable PPV3 (71.7% vs. 61.3%; P = .0717). Mass findings were
      correlated with higher suspicion for cancer than nonmass findings (P < .001).
      There was no significant difference in PPV3 when comparing biopsies from
      homogeneous vs. heterogeneous BPU (72.5% vs. 60.7%; P = .103). No association was
      found between patients' BPU and diagnosed cancer or high-risk lesions (P = .513).
      Biopsies from nondense breasts demonstrated higher PPV3 than biopsies from dense
      breasts (85.4% vs. 60.6%; P = .0025); patients with nondense breasts were more
      likely to be diagnosed with cancer or high-risk pathology (PPV1 = 87.8% vs.
      66.0%; P = .00844). Dense breasts had a greater association with heterogeneous
      BPU (P = .0844). CONCLUSION: Neither variability in mass or nonmass positive MBI
      findings, nor variability in BPU on MBI were significant determinants for the
      probability of malignancy. Dense breasts were associated with lower
      predictability and heterogeneous BPU on MBI.

PMID- 29580792
TI  - Observer Variability in Breast Cancer Diagnosis between Countries with and
      without Breast Screening.
AB  - RATIONAL AND OBJECTIVES: Image reporting is a vital component of patient
      management depending on individual radiologists' performance. Our objective was
      to explore mammographic diagnostic efficacy in a country where breast cancer
      screening does not exist. MATERIALS AND METHODS: Two mammographic test sets were
      used: a typical screening (TS) and high-difficulty (HD) test set. Nonscreening
      (NS) radiologists (n = 11) read both test sets, while 52 and 49 screening
      radiologists read the TS and HD test sets, respectively. The screening
      radiologists were classified into two groups: a less experienced (LE) group with
      <=5 years' experience and a more experienced (ME) group with >=5 years'
      experience. A Kruskal-Wallis and Tukey-Kramer post hoc test were used to compare
      reading performance among reader groups, and the Wilcoxon matched pairs tests was
      used to compare TS and ND test sets for the NS radiologists. RESULTS: Across the
      three reader groups, there were significant differences in case sensitivity (chi2
      [2] = 9.4, P = .008), specificity (chi2 [2] = 10.3, P = .006), location
      sensitivity (chi2 [2] = 19.8, P < .001), receiver operating characteristics, area
      under the curve (chi2 [2] = 19.7, P < .001) and jack-knife free-response receiver
      operating characteristics (JAFROCs) (chi2 [2] = 18.1, P < .001). NS performance
      for all measured scores was significantly lower than those for the ME readers (P
      < .006), while only location sensitivity was lower (chi2 [2] = 17.5, P = .026)
      for the NS compared to the LE group. No other significant differences were
      observed. CONCLUSION: Large variations in mammographic performance exist between
      radiologists from screening and nonscreening countries.

PMID- 29580793
TI  - Comparison of in vivo vs. ex situ obtained material properties of sheep common
      carotid artery.
AB  - Patient-specific biomechanical modelling can improve preoperative surgical
      planning. This requires patient-specific geometry as well as patient-specific
      material properties as input. The latter are, however, still quite challenging to
      estimate in vivo. This study focuses on the estimation of the mechanical
      properties of the arterial wall. Firstly, in vivo pressure, diameter and
      thickness of the arterial wall were acquired for sheep common carotid arteries.
      Next, the animals were sacrificed and the tissue was stored for mechanical
      testing. Planar biaxial tests were performed to obtain experimental stress
      stretch curves. Finally, parameters for the hyperelastic Mooney-Rivlin and Gasser
      Ogden-Holzapfel (GOH) material model were estimated based on the in vivo obtained
      pressure-diameter data as well as on the ex situ experimental stress-stretch
      curves. Both material models were able to capture the in vivo behaviour of the
      tissue. However, in the ex situ case only the GOH model provided satisfactory
      results. When comparing different fitting approaches, in vivo vs. ex situ, each
      of them showed its own advantages and disadvantages. The in vivo approach
      estimates the properties of the tissue in its physiological state while the ex
      situ approach allows to apply different loadings to properly capture the
      anisotropy of the tissue. Both of them could be further enhanced by improving the
      estimation of the stress-free state, i.e. by adding residual circumferential
      stresses in vivo and by accounting for the flattening effect of the tested
      samples ex vivo. * Competing interests: none declared * Word count: 4716.

PMID- 29580794
TI  - Intra-Arterial Fibrinous Sheath Development as a Potential Complication of the
      Impella Ventricular Assist Device.

PMID- 29580795
TI  - Coronary Artery Bypass Grafting Survival is Related to the Duration of
      Postoperative Intubation: Continued Insights From the Surgical Treatment for
      Ischemic Heart Failure (STICH) Trial.

PMID- 29580796
TI  - Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic
      Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a
      Multicenter Randomized Trial.
AB  - OBJECTIVE: Acute kidney injury (AKI) occurs frequently after cardiac surgery.
      Levosimendan might reduce the incidence of AKI in patients undergoing cardiac
      surgery. The authors investigated whether levosimendan administration could
      reduce AKI incidence in a high-risk cardiac surgical population. DESIGN: Post hoc
      analysis of a multicenter randomized trial. SETTING: Cardiac surgery operating
      rooms and intensive care units of 14 centers in 3 countries. PARTICIPANTS: The
      study comprised 90 patients who underwent mitral valve surgery with an estimated
      glomerular filtration rate <60 mL/min/1.73 m2 and perioperative myocardial
      dysfunction. INTERVENTIONS: Patients were assigned randomly to receive
      levosimendan (0.025-0.2 MUg/kg/min) or placebo in addition to standard inotropic
      treatment. MEASUREMENTS AND MAIN RESULTS: Forty-six patients were assigned to
      receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14
      (30%) patients in the levosimendan group versus 23 (52%) in the placebo group
      (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035).
      The incidence of major complications also was lower (18 [39%]) in the
      levosimendan group versus that in the placebo group (29 [66%]) (absolute
      difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum
      creatinine at intensive care unit discharge was observed in the levosimendan
      group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76]
      mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). CONCLUSIONS:
      Levosimendan may improve renal outcome in cardiac surgery patients with chronic
      kidney disease undergoing mitral valve surgery who develop perioperative
      myocardial dysfunction. Results of this exploratory analysis should be
      investigated in future properly designed randomized controlled trials.

PMID- 29580797
TI  - Frailty in Cardiac Surgery.

PMID- 29580798
TI  - The South Asian Origins of the Global Network to Eradicate Blindness: WHO, NGOs,
      and Decentralization.
AB  - The global network to eradicate blindness emerged out of the work of Western and
      South Asian professionals to eradicate smallpox which was endemic in South Asia.
      The history of the emergence of the global network to eradicate blindness
      demonstrates a shift from vertical command and control public health programs
      directed by the WHO, to the decentralized public health services originating in
      non-profit, non-governmental organizations and coordinated by the WHO. The WHO
      constitution started with a federal regionalist structure that encouraged
      collaboration and coordination with NGOs. In South Asia in particular,
      epidemiologists and general medical practitioners moved from eradicating smallpox
      through the WHO to creating their own domestic and international NGOs based in
      various countries with a mission to control blindness in South Asia and Africa.
      In 1975, pushed by the WHO Director General, these new NGOs in turn joined with
      individual ophthalmologists and existing blind member associations to form the
      International Agency for the Prevention of Blindness. Thus, the WHO was shaped
      by, and shaping, international NGOs such as the IAPB. The IAPB pushed for the
      formation of the WHO Prevention of Blindness program. This was the earliest
      example of how the IAPB facilitates bottom-up agenda-setting in the WHO. In 1980,
      when the WHO officially closed the smallpox program, the Prevention of Blindness
      program first received independent funding. Presently, the IAPB acts as a
      decentralized arm of the WHO.

PMID- 29580799
TI  - Gold nanoparticles dispersion stability under dynamic coating conditions in
      capillary zone electrophoresis.
AB  - Capillary zone electrophoresis (CZE) of unmodified gold nanoparticles (Au NPs)
      was investigated in terms of dispersion stability in a presence of buffering
      counter-ions in background electrolyte (BGE). Capillary length, migration time
      and electric field strength were identified among factors influencing particles
      CZE. Moreover, BGE electrolysis was found to significantly affect analyses
      repeatability. The adsorption of NPs to capillary wall was recognized as the main
      problem. It was shown that this inconvenience can be overcome by the application
      of relatively big counter-ions. According to this observation, steric
      stabilization of NPs suspension by BGE components during CZE was hypothesized. In
      result, repeatable CZE of bare Au NPs under dynamic coating conditions was shown.

PMID- 29580800
TI  - Construction of chiral ligand exchange capillary electrochromatography for d,l
      amino acids enantioseparation and its application in glutaminase kinetics study.
AB  - A chiral ligand exchange capillary electrochromatography (CLE-CEC) protocol was
      designed and implemented for d,l-amino acids enantioseparation with poly(maleic
      anhydride-styrene-methacryloyl-l-arginine methyl ester) as the coating. The block
      copolymer was synthesized through the reversible addition fragmentation chain
      transfer reaction. In the constructed CLE-CEC system, poly (methacryloyl-l
      arginine methyl ester) moiety of the block copolymer played the role as the
      immobilized chiral ligand and Zn (II) was used as the central ion. Key factors,
      including pH of buffer solution, ratio of Zn (II) to ligands, the mass ratio of
      monomers in the block copolymer, which affect the enantioresolution were
      investigated. Comparing with the bare capillary, the CLE-CEC enantioresolution
      was enhanced greatly with the coating one. 5 Pairs of d,l-amino acids enantiomers
      obtained baseline separation with 5 pairs partly separated. The mechanism of
      enhancement enantioresolution of the developed CLE-CEC system was explored
      briefly. Further, good linearities were achieved in the range of 25.0 MUM-5.0 mM
      for quantitative analysis of d-glutamine (r2 = 0.997) and l-glutamine (r2 =
      0.991). Moreover, the proposed CLE-CEC assay was successfully applied in the
      kinetics study of glutaminase by using l-glutamine as the substrate.

PMID- 29580801
TI  - Reversible Concanavalin A (Con A) ligands immobilization on metal chelated
      macroporous cellulose monolith and its selective adsorption for glycoproteins.
AB  - The present work deals with the development of novel affinity monolith with
      reversible protein ligands for protein chromatography. As for the formation of
      reversible ligands, Concanavalin A (Con A) is chelated with Cu(II)-iminodiacetic
      acid (IDA) immobilized macroporous cellulose monolith (MCM) for glycoprotein
      adsorption. The reversible immobilization is realized by Cu ions, which bridge
      affinity ligands and support by strong chelation interaction. The fabrication
      process of reversible Con A immobilized adsorbent is studied, especially with
      regards to the effect of synthesis conditions on the ligands immobilization. The
      adsorption behavior is then evaluated to elucidate the potential of Con A-Cu(II)
      IDA-MCM for protein chromatography. It reveals that the static adsorption
      capacity and dissociation constant of glucose oxidase (GOD) on Con A-Cu(II)-IDA
      MCM are determined to be 17.4 +/- 0.6 mg mL-1 and 0.055 +/- 0.011 mg mL-1 by
      Langmuir model. With frontal analysis, the dynamic binding capacity of GOD at 10%
      breakthrough point is about 11.4 +/- 1.0 mg mL-1 and changes less with an
      increase of flow velocity from 0.2 to 1.0 mL min-1. Moreover, Con A-Cu(II)-IDA
      MCM displays weak nonspecific adsorption for the impurities and is able to
      successfully enrich glycoprotein ovalbumin (OVA) from diluted chicken egg white.
      In addition, Con A-Cu(II)-IDA-MCM exhibits excellent stability by the repeated
      adsorption/desorption operations. By taking these advantages of high adsorption
      capacity, excellent specificity and structure stability, the prepared affinity
      adsorbent of Con A-Cu(II)-IDA-MCM has great potential for high performance
      protein chromatography.

PMID- 29580802
TI  - Poly(butylene terephthalate) based novel achiral stationary phase investigated
      under supercritical fluid chromatography conditions.
AB  - Poly(butylene terephthalate) based novel stationary phase (SP), composed of
      planar aromatic phenyl group together with ester group monomer units, was
      designed for supercritical fluid chromatography (SFC) use. As expected from its
      structure, this phase shows planarity recognition of isomeric aromatics and
      closely similar compounds. Interestingly, for most analytes, the retention
      behavior of this SP is significantly distinct from that of the 2-ethylpyridine
      based SPs which is among the most well-known SFC dedicated phases. Although the
      poly(butylene terephthalate) is coated on silica gel, the performance of the
      column did not change by using extended range modifiers such as THF,
      dichloromethane or ethyl acetate and column robustness was confirmed by cycle
      durability testing.

PMID- 29580803
TI  - Childbirth Narratives of Women With Posttraumatic Stress Symptoms in the
      Postpartum Period.
AB  - OBJECTIVE: To examine cognitive, emotional, and perceptual differences in the
      childbirth narratives of women with high levels of posttraumatic stress symptoms
      (PTSS) compared with women with low levels of PTSS in the postpartum period.
      DESIGN: A cross-sectional design. Participants were retrospectively assigned to
      the high or low PTSS group on the basis of their scores on the Perinatal
      Posttraumatic Stress Disorder Questionnaire (PPQ) administered at 1 week and 3
      months after childbirth. SETTING: Participants' homes and Internet survey.
      PARTICIPANTS: Twenty-five women were included in the high PTSS group (PPQ score
      >= 12), and 25 were included in the low PTSS group (PPQ score <= 1). METHODS:
      Participants completed the PPQ and a writing task about the birth experience 1
      week after birth and completed an online version of the PPQ 3 months after birth.
      Characteristics of the narratives were analyzed and compared between the two
      groups using the Linguistic Inquiry Word Count. RESULTS: Compared with
      participants with low levels of PTSS, participants with high levels of PTSS
      reported more negative emotions, including horrific images connected to labor and
      birth and fewer positive emotions. Participants with high levels of PTSS used
      more sensory and perceptual terms (tactile, visual, and auditory). In contrast,
      women with low levels of PTSS described more active participation during birth
      and used more future tense verbs. CONCLUSION: Our findings suggest the aspects
      that are involved in the development and maintenance of PTSS after birth and may
      be considered for use in clinical practice to improve quality of care and women's
      health during the postpartum period.

PMID- 29580804
TI  - Neurometabolite levels in antipsychotic-naive/free patients with schizophrenia: A
      systematic review and meta-analysis of 1H-MRS studies.
AB  - BACKGROUND: Studies using proton magnetic resonance spectroscopy (1H-MRS) have
      reported altered neurometabolite levels in patients with schizophrenia. However,
      results are possibly confounded by the influence of antipsychotic (AP). Thus,
      this meta-analysis aimed to examine neurometabolite levels in AP-naive/free
      patients with schizophrenia. METHODS: A literature search was conducted using
      Embase, Medline, and PsycINFO to identify studies that compared neurometabolite
      levels in AP-naive/free patients with schizophrenia to healthy controls (HCs).
      Eight neurometabolites (glutamate, glutamine, glutamate + glutamine, N
      acetylaspartate [NAA], choline, creatine, myo-inositol, and gamma-Aminobutyric
      acid [GABA]) and seven regions of interest (ROI; medial prefrontal cortex,
      dorsolateral prefrontal cortex, frontal white matter, occipital lobe, basal
      ganglia, hippocampus/medial temporal lobe, and thalamus) were examined. RESULTS:
      Twenty-one studies (N = 1281) were included in the analysis. The results showed
      lower thalamic NAA levels (3 studies, n = 174, effect size = -0.56, P = 0.0005)
      in the patient group. No group differences were identified for other
      neurometabolites. CONCLUSIONS: Our findings suggest that impaired neuronal
      integrity in the thalamus may be a potential trait maker in the early stages of
      schizophrenia.

PMID- 29580805
TI  - Mycoplasma infection and hypoxia initiate succinate accumulation and release in
      the VM-M3 cancer cells.
AB  - Succinate is known to act as an inflammatory signal in classically activated
      macrophages through stabilization of HIF-1alpha leading to IL-1beta production.
      Relevant to this, hypoxia is known to drive succinate accumulation and release
      into the extracellular milieu. The metabolic alterations associated with
      succinate release during inflammation and under hypoxia are poorly understood.
      Data are presented showing that Mycoplasma arginini infection of VM-M3 cancer
      cells enhances the Warburg effect associated with succinate production in
      mitochondria and eventual release into the extracellular milieu. We investigated
      how succinate production and release was related to the changes of other soluble
      metabolites, including itaconate and 2-HG. Furthermore, we found that hypoxia
      alone could induce succinate release from the VM-M3 cells and that this could
      occur in the absence of glucose-driven lactate production. Our results elucidate
      metabolic pathways responsible for succinate accumulation and release in cancer
      cells, thus identifying potential targets involved in both inflammation and
      hypoxia. This article is part of a Special Issue entitled 20th European
      Bioenergetics Conference, edited by Laszlo Zimanyi and Laszlo Tretter.

PMID- 29580807
TI  - Immunogenicity and antitumor activity of the superlytic lambdaF7 phage
      nanoparticles displaying a HER2/neu-derived peptide AE37 in a tumor model of
      BALB/c mice.
AB  - Phage display technique has been increasingly researched for vaccine design and
      delivery strategies in recent years. In this study, the AE37 (Ii-Key/HER-2/neu
      776-790) peptide derived from HER2 (human epidermal growth factor receptor
      protein) was used as a fused peptide to the lambda phage (lambdaF7) coat protein
      gpD, and the phage nanoparticles were used to induce antitumor immunogenicity in
      a TUBO model of breast cancer in mice. Mice were immunized with the AE37 peptide
      displaying phage, lambdaF7 (gpD::AE37) every 2-week intervals over 6-weeks, then
      the generated immune responses were evaluated. An induction of CTL immune
      response by the lambdaF7 (gpD::AE37) construct compared to the control lambdaF7
      and buffer groups was observed in vitro. Moreover, in the in vivo studies, the
      vaccine candidate showed promising prophylactic and therapeutic effects against
      the HER2 overexpressing cancer in BALB/c mice.

PMID- 29580806
TI  - Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514,
      to suppress breast cancer progression and lung metastasis.
AB  - Metastasis is a major cause of breast cancer-associated mortality. Natural
      products extracted from herbs provide rich bioactive compounds with anticancer
      efficacy but may have limited or moderate potency and considerable toxicity. We
      developed a novel aziridonin, YD0514, by aziridinating oridonin, a natural
      product of the medicinal herb Rabdosia rubescens. In this study, we found that
      YD0514 significantly inhibited proliferation, motility, and adhesion of
      metastatic breast cancer cell lines MDA-MB-231, GI101, GILM2, and GILM3. YD0514
      also decreased the protein expression of matrix metalloproteinases 2 and 9 (MMP2
      and MMP9), focal adhesion kinase (FAK), and integrin family members. Importantly,
      YD0514 suppressed the growth of metastatic breast cancer xenograft tumors and
      significantly inhibited lung metastasis in vivo. Lastly, we showed that YD0514's
      anti-metastatic effect on highly aggressive breast cancer is mediated via
      regulating the NRF-2/RHOA/ROCK signaling pathway. These results demonstrate that
      YD0514, the first active analog based on an oridonin D-ring modification, has the
      potential to be developed as an anti-metastasis therapy for patients with
      metastatic cancers.

PMID- 29580808
TI  - Basement membrane destruction by pancreatic stellate cells leads to local
      invasion in pancreatic ductal adenocarcinoma.
AB  - Stroma invasion is an important step in pancreatic cancer progression. However,
      how pancreatic ductal adenocarcinoma (PDAC) with ductal structure invades the
      surrounding stroma has not been clear. Here, we elucidated the mechanism of
      stromal invasion of PDAC, using organoids. From resected PDAC specimens, we
      established human PDAC organoids, which developed ductal and basement membrane
      (BM) structures. When the organoids were co-cultured with pancreatic stellate
      cells (PSCs) in a collagen matrix, organoids lost their BM and ductal structures,
      and invaded collagen matrix more frequently than did mono-cultured organoids.
      Interestingly, direct contact by PSCs to PDAC organoids was observed before BM
      destruction. Matrix metalloproteinase (MMP) 2 or membrane type-1 MMP (MT1MMP)
      knockdown in PSCs significantly attenuated BM destruction by PSCs, and retained
      the ductal structures in organoids. Our results imply that direct contact by PSCs
      induces BM destruction and stromal invasion of PDAC via MMP2 which binds to
      MT1MMP on PSCs.

PMID- 29580809
TI  - Commentary regarding Gannon et al. "Viral infections and breast cancer - A
      current perspective".

PMID- 29580810
TI  - Accurate detection and quantification of epigenetic and genetic second hits in
      BRCA1 and BRCA2-associated hereditary breast and ovarian cancer reveals multiple
      co-acting second hits.
AB  - BACKGROUND: This study characterizes the second hit spectrum in BRCA1 and BRCA2
      associated breast and ovarian cancers at both gene loci to investigate if second
      hit mechanisms are mutually exclusive or able to coincide within the same tumor.
      METHODS: Loss of heterozygosity, somatic point mutations and copy number
      alterations along with promoter methylation were studied in 56 breast and 15
      ovarian cancers from BRCA1 and BRCA2 germline mutation carriers. A mathematical
      methodology was introduced to quantify the tumor cell population carrying a
      second hit. RESULTS: Copy neutral LOH was the most prevalent LOH mechanism in
      this cohort (BC 69%, OC 67%). However, only 36% of BC and 47% of OC showed LOH in
      all cancerous cells. Somatic intragenic deletions and methylated subclones were
      also found in combination with (partial) loss of heterozygosity. Unequivocal
      deleterious somatic point mutations were not identified in this cohort.
      CONCLUSION: Different mechanisms inactivating the wild type allele are present
      within the same tumor sample at various extents. Results indicate that BRCA1/2
      linked breast and ovarian cancer cells are predominantly characterized by LOH,
      but harbor a complex combination of second hits at various frequencies.

PMID- 29580811
TI  - Characterizing alleles with large deletions using region specific extraction.
AB  - Two novel HLA class II alleles, DRB4*03:01N and DQB1*03:276N, containing large
      deletions were identified during routine typing. Extraction of DNA encompassing
      the deletions was carried out with a panel of capture oligonucleotides followed
      by whole genome amplification. Next generation DNA sequencing was then used to
      characterize the sequences. DRB4*03:01N has a 16 kilobase pair deletion
      stretching upstream from intron 2 toward centromeric DRB8. DQB1*03:276N has two
      deletions separated by 844 nucleotides. The first deletion (3.7 kilobase pairs)
      is upstream of intron 1 and the second deletion removes 3.3 kilobase pairs
      further upstream towards centromeric DQA2.

PMID- 29580812
TI  - DDX3 in HIV-1 infection and sensing: A paradox.
AB  - HIV-1 sensors and their signaling features have been an ongoing topic of intense
      research over the last decade, as these mechanisms fail to establish protective
      immunity against HIV-1. Here, we discuss how HIV-1 infects dendritic cells (DCs)
      and which sensors play a role in recognizing viral DNA and RNA in these
      specialized immune cells. We will elaborate on the RNA helicase DDX3, which is
      crucial in translation initiation of HIV-1 mRNA, but also fulfills an important
      role as RNA sensor and inducer of antiviral immunity in DCs. As DDX3 is
      indispensable for HIV-1 replication, the virus cannot escape sensing by DDX3,
      which is an important aspect of its function. Last but not least, we will discuss
      how HIV-1 suppresses DDX3 sensing and how this impacts the viral load in HIV-1
      infected individuals.

PMID- 29580813
TI  - Association between impaired IL-10 production following exposure to
      Staphylococcus aureus enterotoxin B and disease severity in eosinophilic chronic
      rhinosinusitis.
AB  - BACKGROUND: IL-10 is a major anti-inflammatory cytokine that prevents
      inflammation-mediated tissue damage. We characterized the production of IL-10 by
      sinonasal tissue cells following exposure to Staphylococcus aureus enterotoxin B
      (SEB), which elicits cellular responses and is associated with the pathogenesis
      of eosinophilic chronic rhinosinusitis (ECRS). METHODS: Dispersed nasal polyp
      (NP) cells and uncinate tissue (UT) cells were prepared from patients with CRS
      with and without NP, respectively. Cells were incubated with SEB, and then the
      levels of IL-10 in the cell supernatants were determined. The effect of
      neutralizing IL-10 on SEB-induced IL-5, IL-13, IFN-gamma, and IL-17A production
      was examined. Expression of IL-10 in NPs was also determined. RESULTS: IL-10 was
      expressed in infiltrating inflammatory cells in NPs. NP cells, especially non
      adherent NP cells, produced substantial amounts of IL-10 in response to SEB.
      Although baseline production of IL-10 was significantly higher in NP cells than
      UT cells, the degree of IL-10 response to SEB was not significantly different
      between the cell types. The degree of IL-10 production was negatively correlated
      with the degree of eosinophilia both in tissues and peripheral blood whereas
      positively correlated with the 1-s forced expiratory volume/forced vital capacity
      ratio. Patients with severe ECRS displayed a significant decrease in IL-10
      production compared with those with non-ECRS. IL-10 neutralization significantly
      augmented SEB-induced IL-13 and IFN-gamma production by NP cells. CONCLUSIONS:
      Impaired IL-10 production in response to SEB in NP may exacerbate the
      pathophysiology of ECRS including eosinophilia and lower airway obstruction.

PMID- 29580814
TI  - Development and Evaluation of a New Formative Assessment of Surgical Performance.
AB  - BACKGROUND: Formative assessment of operative performance is a mandatory part of
      surgical training. Engagement with assessment is limited in part by the time
      consuming nature and the high perceived stakes of current assessment tools.
      OBJECTIVES: Our aims were to develop and collect validity evidence for a new
      operative assessment tool that addresses barriers to assessment that current
      trainers and trainees experience. METHODS: We developed the Generic Operative
      Supervised Learning Event (GOSLE). Orthopedic trainees were invited to complete
      GOSLEs with their trainers after surgical procedures. Experienced consultants
      assessed videotaped operations performed by trainees using the GOSLE. Validity
      evidence for content, relationships to other scores, internal structure, response
      process, and consequences of testing were evaluated. RESULTS: A total of 250
      GOSLEs were completed. A strong correlation was found between the GOSLE scores
      and the Procedure-Based Assessment ratings (r = 0.87, p < 0.001). Rasch analysis
      confirmed satisfactory internal structure of the rating scale, with sequential
      increases in rating as performance improved. The reproducibility coefficient was
      0.88, with 10 assessments of the same trainee who has to achieve a reliability
      coefficient of 0.8. Over 90% of users found the GOSLE easy to use, with most
      preferring it to other assessment methods. Feedback quality was higher using the
      GOSLE than with current assessments. CONCLUSION: We have collected validity
      evidence across multiple domains in support of the GOSLE. Its psychometric
      performance is comparable to that of current assessments. It is preferred by
      trainers and trainees over existing assessments. It stimulates high-quality,
      actionable feedback which better supports formative assessment. By addressing
      issues experienced with existing assessments, we expect engagement among users to
      be high.

PMID- 29580815
TI  - Age dependent variations in the deep brain photoreceptors (DBPs), GnRH-GnIH
      system and testicular steroidogenesis in Japanese quail, Coturnix coturnix
      japonica.
AB  - The complex physiology of aging involves a number of molecular and biochemical
      events, manifested as signs of senescence. Japanese quail is a very unique and
      advantageous model to study the signs and symptoms of senescence in the central
      and peripheral modules of HPG axis. In the present study, we have investigated
      the age dependent variations in hypothalamic deep brain photoreceptors (DBPs),
      central GnRH-I/II-GnIH-Mel1cR system, testicular GnRH-GnIH system, testicular
      steroidogenic genes and proteins, androgen receptor (AR) and serum testosterone
      level in quail of different age groups [3-wk (sexually immature), 6-wk (sexually
      mature and crossed the puberty), 16-wk (adult, sexually active and showing full
      breeding phase) and 144-wk (aged)]. Findings of our present study showed the
      differential expression of these genes/proteins in quail of different age groups.
      The low levels of the DBPs, GnRH-I, GnIH, Mel1cR in hypothalamus and GnRH-II in
      midbrain, significantly decreased testicular GnRH/GnRH-R-GnIH, steroidogenic
      genes/proteins and serum testosterone were observed in immature quail. The
      significantly increased expression of opsins in the DBPs, GnRH-I, GnIH, Mel1cR in
      hypothalamus and GnRH-II in midbrain influences the testicular GnRH-GnIH and
      stimulate the testicular steroidogenesis in mature and adult quail. In aged
      quail, the significantly decreased levels of hypothalamic DBPs, GnRH-I, GnIH,
      Mel1cR and midbrain GnRH-II modulates the testicular GnRH-GnIH and further
      suppresses the genes/proteins involved in steroidogenesis and results in reduced
      serum testosterone. Hence, it can be concluded from our findings that the
      testicular steroidogenesis and its neuroendocrine regulation varies with age, in
      Japanese quail.

PMID- 29580816
TI  - Overexpression of Egr2 and Egr4 protects rat brains against ischemic stroke by
      downregulating JNK signaling pathway.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of Egr2 and
      Egr4 upregulation on ischemic stroke recovery of rats. METHODS: In this study,
      Sprague Dawley (SD) rats assigned at random into control, sham and MCAO (middle
      cerebral artery occlusion) group were treated accordingly to build MCAO models.
      The neurological severity scores (NSS) test was applied to assess rats' behavior.
      Triphenyltetrazolium chloride (TTC) staining reflected infarct areas while Nissl
      staining revealed the number of neurons. Levels of pro-inflammatory cytokines
      (interleukin [IL]-1beta, IL-6 and tumor necrosis factor [TNF]-alpha) were judged
      by enzyme-linked immunosorbent assay (ELISA) in brain and serum tissues. We
      applied western blot to check the expression of Egr2, Egr4 and JNK/c-JUN (c-Jun N
      terminal kinase) pathway. Further grouping of rats were based on various
      transfection, requiring control, sham, MCAO, MCAO + Egr2 cDNA (complementary
      DNA), MCAO + Egr4 cDNA, MCAO + Egr2 cDNA + Egr4 cDNA group to observe difference
      in MCAO recovery and JNK/c-JUN-pathway-related protein expression. RESULTS: Under
      successful modeling of MCAO, western blot results suggested down-regulation of
      Egr2 and Egr4 and overexpression of pro-inflammatory cytokines. The JNK/c-JUN
      pathway was activated. On upregulation of Egr2 and Egr4 in infarct areas,
      neurological function of SD rats recovered along with repressed JNK/c-JUN pathway
      activation and increased neuron number. CONCLUSION: Upregulation of Egr2 and Egr4
      could demote the activation of JNK/c-JUN pathway and the expression of pro
      inflammatory cytokines in MCAO rats, so that Egr2 and Egr4 might be potential
      targets for ischemic stroke in future.

PMID- 29580817
TI  - Concrete action now: UN High-Level Meeting on Tuberculosis.

PMID- 29580818
TI  - Tuberculosis: advances and challenges in development of new diagnostics and
      biomarkers.
AB  - Tuberculosis remains the leading cause of death from an infectious disease
      worldwide. Early and accurate diagnosis and detection of drug-sensitive and drug
      resistant tuberculosis is essential for achieving global tuberculosis control.
      Despite the introduction of the Xpert MTB/RIF assay as the first-line rapid
      tuberculosis diagnostic test, the gap between global estimates of incidence and
      new case notifications is 4.1 million people. More accurate, rapid, and cost
      effective screening tests are needed to improve case detection. Diagnosis of
      extrapulmonary tuberculosis and tuberculosis in children, people living with HIV,
      and pregnant women remains particularly problematic. The diagnostic molecular
      technology landscape has continued to expand, including the development of tests
      for resistance to several antituberculosis drugs. Biomarkers are urgently needed
      to indicate progression from latent infection to clinical disease, to predict
      risk of reactivation after cure, and to provide accurate endpoints for drug and
      vaccine trials. Sophisticated bioinformatic computational tools and systems
      biology approaches are being applied to the discovery and validation of
      biomarkers, with substantial progress taking place. New data have been generated
      from the study of T-cell responses and T-cell function, serological studies, flow
      cytometric-based assays, and protein and gene expression studies. Alternative
      diagnostic strategies under investigation as potential screening and triaging
      tools include non-sputum-based detection with breath-based tests and automated
      digital radiography. We review developments and key achievements in the search
      for new tuberculosis diagnostics and biomarkers. We highlight gaps and challenges
      in evaluation and rollout of new diagnostics and biomarkers, and prioritise areas
      needing further investment, including impact assessment and cost-benefit studies.

PMID- 29580819
TI  - Tuberculosis: progress and advances in development of new drugs, treatment
      regimens, and host-directed therapies.
AB  - Tuberculosis remains the world's leading cause of death from an infectious
      disease, responsible for an estimated 1 674 000 deaths annually. WHO estimated
      600 000 cases of rifampicin-resistant tuberculosis in 2016-of which 490 000 were
      multidrug resistant (MDR), with less than 50% survival after receiving
      recommended treatment regimens. Concerted efforts of stakeholders, advocates, and
      researchers are advancing further development of shorter course, more effective,
      safer, and better tolerated treatment regimens. We review the developmental
      pipeline and landscape of new and repurposed tuberculosis drugs, treatment
      regimens, and host-directed therapies (HDTs) for drug-sensitive and drug
      resistant tuberculosis. 14 candidate drugs for drug-susceptible, drug-resistant,
      and latent tuberculosis are in clinical stages of drug development; nine are
      novel in phase 1 and 2 trials, and three new drugs are in advanced stages of
      development for MDR tuberculosis. Specific updates are provided on clinical
      trials of bedaquiline, delamanid, pretomanid, and other licensed or repurposed
      drugs that are undergoing investigation, including trials aimed at shortening
      duration of tuberculosis treatment, improving treatment outcomes and patient
      adherence, and reducing toxic effects. Ongoing clinical trials for shortening
      tuberculosis treatment duration, improving treatment outcomes in MDR
      tuberculosis, and preventing disease in people with latent tuberculosis infection
      are reviewed. A range of HDTs and immune-based treatments are under investigation
      as adjunctive therapy for shortening duration of therapy, preventing permanent
      lung injury, and improving treatment outcomes of MDR tuberculosis. We discuss the
      HDT development pipeline, ongoing clinical trials, and translational research
      efforts for adjunct tuberculosis treatment.

PMID- 29580820
TI  - Plant food allergy: Influence of chemicals on plant allergens.
AB  - Plant-derived foods are the most common allergenic sources in adulthood. Owing to
      the rapidly increasing prevalence of plant food allergies in industrialized
      countries, the environmental factors are suspected to play a key role in
      development of allergic sensitization. The present article provides an overview
      of ways by which chemicals may influence the development and severity of allergic
      reactions to plant foods, with especial focus on plant allergens up-regulated
      under chemical stress. In plants, a substantial part of allergens have defense
      related function and their expression is highly influenced by environmental
      stress and diseases. Pathogenesis-related proteins (PR) account for about 25% of
      plant food allergens and some are responsible for extensive cross-reactions
      between plant-derived foods, pollen and latex allergens. Chemicals released by
      anthropogenic sources such as agriculture, industrial activities and traffic
      related air pollutants are potential drivers of the increasing sensitization to
      allergenic PRs by elevating their expression and by altering their immunogenicity
      through post-translational modifications. In addition, some orally-taken
      chemicals may act as immune adjuvants or directly trigger non-IgE mediated food
      allergy. Taken together, the current literature provides an overwhelming body of
      evidence supporting the fact that plant chemical exposure and chemicals in diet
      may enhance the allergenic properties of certain plant-derived foods.

PMID- 29580821
TI  - PAHs in seafood from the Mediterranean Sea: An exposure risk assessment.
AB  - Seafood represent an important food source for human, and seafood quality is
      associated with marine environment quality. PAHs are one of the main organic
      environmental contaminants and they can be introduced into the body through
      different way (ingestion, inhalation, dermal absorption). We present data on
      bioaccumulation of the sixteen PAHs, defined priority by the U.S.- EPA, in
      Sardina pilchardus, Solea solea and Donax trunculus, three species caught in the
      Catania Gulf and highly consumed by the local population. The risk to develop
      chronic systemic and carcinogenic effects due to the consumption of these target
      species was evaluated through the EDI, THQ and CR. EDI derived from D. trunculus
      ingestion falls within the range calculated by the EFSA. The THQ is less than 1,
      and the CR calculated for the Benzo(a)Pyrene is at the limit of the ARL (1?10-5).
      EDI derived from S. pilchardus and S. solea ingestion are below the range
      calculated by the EFSA. The THQ is less than 1, and the CR is below the
      acceptable risk level. The contamination level found in local seafood determines
      a low risk to develop chronic systemic effects, but the cancer risk could be of
      health concern especially for high-frequency molluscs consumers.

PMID- 29580822
TI  - Dietary exposure to cadmium and health risk assessment in children - Results of
      the French infant total diet study.
AB  - Besides specific occupational activities or smoking, food is the main route of
      cadmium exposure for the general population. In France a total diet study
      previously conducted for adults and children over 3 years old revealed that
      health concerns due to Cd dietary exposure existed for both adults and children.
      This study showed that the Cd tolerable weekly intake, based on potential
      nephrotoxicity effects, is exceeded by a high proportion of children under 3
      years old. Nephrotoxicity results from the accumulation of cadmium in the kidney
      and appears typically after long-term exposure (40-50 years). Despite the
      exceeding of the tolerable weekly intake observed during the first three years of
      childhood, due to low body weights compared to adults, the accumulation rate of
      cadmium is much lower during the whole childhood period (from 0 to 17 years of
      age) than during adulthood. These data suggest that dietary exposure to cadmium
      should be reduced for both children and adults to prevent health concerns
      associated with nephrotoxicity in later life. Moreover, recent literature
      suggests that Cd can induce other adverse health effects (especially endocrine
      disruption or neurotoxicity) that could be triggered at even lower doses than
      those triggering nephrotoxicity.

PMID- 29580823
TI  - GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by
      improving hepatic energy metabolism in high-fat diet fed mice.
AB  - Endoplasmic reticulum (ER) stress and hepatic steatosis are intertwined with
      insulin resistance. PPARs are at the crossroads of these pathways. This study
      aimed to investigate the effects of GW0742 (PPAR-beta agonist) on hepatic energy
      metabolism and ER stress in a murine diet-induced obesity model. HF diet caused
      overweight, hyperinsulinemia, hepatic inflammation (increased NF-kB, TNF-alpha,
      and IL-6 protein expression) and favored hepatic lipogenesis, leading to ER
      stress, with ultrastructural and molecular alterations, ending up in proapoptotic
      stimulus. GW0742 rescued the overweight and the glucose tolerance, tackled
      hepatic inflammation and favored hepatic beta-oxidation over lipogenesis. These
      results comply with ER ultrastructure improvement, reducing ER stress and
      apoptosis in treated animals. Our results indicate that the PPAR-beta/delta
      activation alleviated the ER stress by improving the insulin sensitivity and
      maximizing the hepatic energy metabolism with a shift towards beta-oxidation.
      PPAR-beta/delta activation could be an essential tool to avoid the NAFLD
      progression and other obesity constraints.

PMID- 29580824
TI  - ESR2 regulates granulosa cell genes essential for follicle maturation and
      ovulation.
AB  - Estrogen receptor 2 (ESR2) plays a critical role in folliculogenesis and
      ovulation. Disruption of ESR2-function in the rats results in female infertility
      due to failure of ovulation. Ovulation failure occurred in two distinct rat
      models, a null mutant and a DNA binding domain (DBD) mutant of ESR2, indicating
      that transcriptional regulation by ESR2 is indispensable for ovulation. To define
      the regulatory role of ESR2 in preovulatory follicular maturation and ovulation,
      we investigated ovarian responsiveness to exogenous gonadotropins in prepubertal
      females. Granulosa cells (GCs) play a vital role in follicle maturation and
      ovulation, and ESR2-dependent estrogen signaling is predominant in GCs,
      therefore, we examined the differential expression of gonadotropin-induced genes
      in GCs. Of 32,623 genes detected by RNA-sequencing, 1696 were differentially
      expressed in Esr2-mutant rats (789 downregulated, and 907 upregulated, absolute
      fold change 2, FDR p < 0.05). Molecular pathway analyses indicated that these
      differentially expressed genes are involved in steroidogenesis, follicle
      maturation, and ovulation. Many of these genes are known regulators of ovarian
      function and a subset were also disrupted in Esr2-mutant mice. Interestingly,
      Kiss1 was identified as one of the differentially expressed genes implicating a
      potential role within the follicle and its regulation by ESR2. Our findings
      indicate that ESR2 regulates key genes in GCs that are essential for follicle
      maturation and ovulation in the rat.

PMID- 29580825
TI  - PIWI-piRNA pathway: Setting the pace of aging by reducing DNA damage.
AB  - Transposable elements (TEs) are powerful drivers of genome evolutionary dynamics
      but are principally deleterious to the host organism by compromising the
      integrity and function of the genome. The transposition of TEs may result in
      mutations and DNA damage. DNA double-strand breaks (DSBs), which may be caused by
      the transposition, are one of the processes directly linked to aging. TEs may
      thus be considered to constitute an internal source of aging and the frequency of
      transposition may, in turn, be considered to affect the pace of aging. The PIWI
      piRNA pathway is a widespread strategy used by most animals to effectively
      suppress transposition. Interestingly, the PIWI-piRNA pathway is expressed
      predominantly in the animal germline, a more or less continuous immortal lineage
      set aside after the first few cell divisions of a developing embryo. Recent
      findings further imply that the PIWI-piRNA pathway and TE suppression constitute
      an important mechanism regulating aging. This article discusses the proposed role
      of the PIWI-piRNA pathway in setting the pace of aging as well as the possible
      mechanisms underlying this process.

PMID- 29580826
TI  - Protein aggregates and proteostasis in aging: Amylin and beta-cell function.
AB  - The ubiquitin-proteasomal-system (UPS) and the autophagy-lysosomal-system (ALS)
      are both highly susceptible for disturbances leading to the accumulation of
      cellular damage. A decline of protein degradation during aging results in the
      formation of oxidatively damaged and aggregated proteins finally resulting in
      failure of cellular functionality. Besides protein aggregation in response to
      oxidative damage, amyloids are a different type of protein aggregates able to
      distract proteostasis and interfere with cellular functionality. Amyloids are
      clearly linked to the pathogenesis of age-related degenerative diseases such as
      Alzheimer's disease. Human amylin is one of the peptides forming fibrils in beta
      sheet conformation finally leading to amyloid formation. In contrast to rodent
      amylin, human amylin is prone to form amyloidogenic aggregates, proposed to play
      a role in the pathogenesis of Type 2 Diabetes by impairing beta-cell
      functionality. Since aggregates such as lipofuscin and beta-amyloid are known to
      impair proteostasis, it is likely to assume similar effects for human amylin. In
      this review, we focus on the effects of IAPP on UPS and ALS and their role in
      amylin degradation, since both systems play a crucial role in maintaining
      proteome balance thereby influencing, at least in part, cellular fate and aging.

PMID- 29580827
TI  - Dual antiplatelet therapy versus single antiplatelet therapy after transaortic
      valve replacement: Meta-analysis.
AB  - BACKGROUND: The current guidelines recommend empirical therapy with DAPT of
      aspirin and clopidogrel for six months after TAVR. This recommendation is based
      on expert consensus only. Giving the lack of clear consensus on treatment
      strategy following TAVR. Goal of this meta-analysis is to assess the efficacy and
      safety of mono-antiplatelet therapy (MAPT) versus dual antiplatelet therapy
      (DAPT) following transcatheter aortic valve replacement (TAVR). METHODS AND
      MATERIALS: We performed a meta-analysis from randomized clinical trials (RCTs)
      and prospective studies that tested DAPT vs. MAPT for all-cause mortality and
      major bleeding of 603 patients. The primary efficacy outcomes were 30 days
      mortality and stroke. The primary safety outcomes were major bleeding and major
      vascular complications. RESULTS: We included 603 patients from 4 studies. The use
      of MAPT was associated with similar mortality rate (5.9% vs. 6.6%; RR = 0.92; 95%
      CI 0.49-1.71; P = 0.68) and stroke rate compared with DAPT (1.3% vs. 1.3%; RR
      1.04; 95% CI 0.27 to 4.04; P = 0.81). There was no difference in major vascular
      complication (4.2% vs. 8.9%; RR 0.52; 95% CI 0.23 to 1.18; P = 0.17) or minor
      vascular complication (4.2% vs. 7.3%; RR 0.58; 95% CI 0.25 to 1.34; P = 0.14).
      However, MAPT was associated with significantly less risk of major bleeding (4.9%
      vs. 14.5%; RR 0.37; 95% CI 0.20 to 0.70; P < 0.01) but no difference in minor
      bleeding (4.2% vs. 3.6%; RR 1.16; 95% CI 0.43 to 3.10; P = 0.85). CONCLUSION:
      MAPT use after TAVR is associated with lower rates of major bleeding compared
      with DAPT with no significant difference in mortality, stroke or vascular
      complications.

PMID- 29580828
TI  - Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate
      with pulmonary function decline.
AB  - BACKGROUND: To characterize glucose patterns with continuous glucose monitoring
      (CGM) in cystic fibrosis (CF) and assess relationships between CGM and clinical
      outcomes. METHODS: 110 CF youth and healthy controls (HC), 10-18 years, wore CGM
      up to 7 days. Correlations between CGM and lung function and BMI z-score change
      over the prior year were determined. RESULTS: Multiple CGM measures were higher
      in CF Normal Glycemic (CFNG) youth versus HC (peak glucose, excursions >140
      mg/dl/day, %time > 140 mg/dl, standard deviation (SD) and mean amplitude of
      glycemic excursions (MAGE)). Hypoglycemia was no different among groups. In CF,
      decline in FEV1% and FVC% correlated with maximum CGM glucose, excursions >200
      mg/dl/day, SD, and MAGE. CONCLUSIONS: CFNG youth have higher glucoses and glucose
      variability than HC on CGM. Higher and more variable glucoses correlate with lung
      function decline. Whether earlier treatment of CGM abnormalities improves lung
      function in CF requires further study.

PMID- 29580829
TI  - Sweat test for cystic fibrosis: Wearable sweat sensor vs. standard laboratory
      test.
AB  - BACKGROUND: Sweat chloride testing for diagnosis of cystic fibrosis (CF) involves
      sweat induction, collection and handling, and measurement in an analytical lab.
      We have developed a wearable sensor with an integrated salt bridge for real-time
      measurement of sweat chloride concentration. Here, in a proof-of-concept study,
      we compare the performance of the sensor to current clinical practice in CF
      patients and healthy subjects. METHOD: Sweat was induced on both forearms of 10
      individuals with CF and 10 healthy subjects using pilocarpine iontophoresis. A
      Macroduct sweat collection device was attached to one arm and sweat was collected
      for 30 min and then sent for laboratory analysis. A sensor was attached to the
      other arm and the chloride ion concentration monitored in real time for 30 min
      using a Bluetooth transceiver and smart phone app. RESULTS: Stable sweat chloride
      measurements were obtained within 15 min following sweat induction using the
      wearable sensor. We define the detection time as the time at which the standard
      deviation of the real-time chloride ion concentration remained below 2 mEq/L for
      5 min. The sweat volume for sensor measurements at the detection time was 13.1 +/
      11.4 MUL (SD), in many cases lower than the minimum sweat volume of 15 MUL for
      conventional testing. The mean difference between sweat chloride concentrations
      measured by the sensor and the conventional laboratory practice was 6.2 +/- 9.5
      mEq/L (SD), close to the arm-to-arm variation of about 3 mEq/L. The Pearson
      correlation coefficient between the two measurements was 0.97 highlighting the
      excellent agreement between the two methods. CONCLUSION: A wearable sensor can be
      used to make real-time measurements of sweat chloride within 15 min following
      sweat induction, requiring a small sweat volume, and with excellent agreement to
      standard methods.

PMID- 29580831
TI  - Commentary on "A Feasibility Study of a New Unibody Branched Stent Graft Applied
      to Reconstruct the Canine Aortic Arch".

PMID- 29580830
TI  - Myocardial Injury is More Common than Deep Venous Thrombosis after Vascular
      Surgery and is Associated with a High One Year Mortality Risk.
AB  - OBJECTIVE/BACKGROUND: Venous thromboembolism (VTE) has been considered the
      dominant major life threatening vascular complication after non-cardiac surgery,
      but recent studies have shifted the emphasis toward myocardial injury after non
      cardiac surgery (MINS) as a common adverse event in the peri-operative setting.
      The aim of the present study was to compare the incidence and influence on
      mortality of two dominant venous and arterial events in the peri-operative period
      by prospectively screening a consecutive cohort of patients undergoing vascular
      surgery. METHODS: This was a sub-study of Vascular Events In Non-cardiac Surgery
      Patients Cohort Evaluation (VISION), the main objective of which was to evaluate
      major peri-operative complications after non-cardiac surgery. Patients undergoing
      vascular surgery had their blood collected to measure the Roche fifth generation
      high sensitivity troponin T (hsTnT) assay before and four times after surgery (6
      12 h post-operatively, on the first, second, and third day following the
      procedure). MINS was defined as an elevated post-operative hsTnT >=65 ng/L or an
      hsTnT >=20 to <65 ng/L with an absolute change of >=5 ng/L that was judged to be
      due to ischaemia. All patients underwent ultrasound venous compression testing
      for deep vein thrombosis (DVT) before, 4, and 7 days after surgery and follow-up
      was performed by telephone 30 days and 1 year after surgery. RESULTS: In total,
      164 consecutive patients were included in this sub-study. MINS was diagnosed in
      39 patients (23.8%) and DVT in four patients (2.4%). The 1 year mortality was
      higher in MINS (9/39 [23.1%]) than non-MINS patients (9/125 [7.2%]; p = .006).
      None of the patients who developed DVT died in the first year after surgery.
      CONCLUSION: MINS is a common complication after vascular surgery. It occurs more
      frequently than DVT and is associated with high 1 year mortality.

PMID- 29580832
TI  - Response to Commentary on "Five-year Results of Great Saphenous Vein Treatment: A
      Meta-analysis".

PMID- 29580833
TI  - Association between physical activity and walking capacity with cognitive
      function in peripheral artery disease patients.
AB  - OBJECTIVE: To identify the association between objectively measured physical
      activity and walking capacity with cognitive function in patients with
      symptomatic peripheral artery disease. METHODS: This was an observational, cross
      sectional study. One hundred and thirty patients (age 67 +/- 8 years) were
      recruited at a tertiary centre specializing in vascular disease. Cognitive
      function (global, memory, executive function and attention) was evaluated using
      the Montreal Cognitive Assessment tool. Physical activity levels (total, light,
      and moderate-vigorous) were obtained using an accelerometer. A 6 min and 4 m walk
      test were undertaken to assess walking capacity. Crude and covariate adjusted,
      linear regression analyses confirmed significant associations between physical
      activity levels and walking capacity with cognitive function. RESULTS: Positive
      and significant associations were observed between moderate to vigorous physical
      activity (p = .039) and walking capacity (p = .030) with memory after adjusting
      for covariates. No significant association was identified between light physical
      activity and usual gait speed with any cognitive function outcome. CONCLUSION:
      Greater memory performance was associated with greater moderate to vigorous
      physical activity levels and walking capacity in patients with symptomatic
      peripheral artery disease. Clinical interventions focused on improving moderate
      to vigorous physical activity levels and walking capacity may provide important
      therapies to potentially enhance cognitive health in patients with peripheral
      artery disease.

PMID- 29580834
TI  - Niemann-Pick C2 protein regulates sterol transport between plasma membrane and
      late endosomes in human fibroblasts.
AB  - Niemann-Pick disease type C2 is a lipid storage disorder in which mutations in
      the NPC2 protein cause accumulation of lipoprotein-derived cholesterol in late
      endosomes and lysosomes (LE/LYSs). Whether cholesterol delivered by other means
      to NPC2 deficient cells also accumulates in LE/LYSs is currently unknown. We show
      that the close cholesterol analog dehydroergosterol (DHE), when delivered to the
      plasma membrane (PM) accumulates in LE/LYSs of human fibroblasts lacking
      functional NPC2. We measured two different time scales of sterol diffusion; while
      DHE rich LE/LYSs moved by slow anomalous diffusion in disease cells (D ~ 4.6?10-4
      MUm2/sec; alpha~0.76), a small pool of sterol could exchange rapidly with D ~ 3
      MUm2/s between LE/LYSs, as shown by fluorescence recovery after photobleaching
      (FRAP). By quantitative lipid mass spectrometry we found that esterification of
      13C-labeled cholesterol but not of DHE is reduced 10-fold in disease fibroblasts
      compared to control cells. Internalized NPC2 rescued the sterol storage phenotype
      and strongly expanded the dynamic sterol pool seen in FRAP experiments. Together,
      our study shows that cholesterol esterification and trafficking of sterols
      between the PM and LE/LYSs depends on a functional NPC2 protein. NPC2 likely acts
      inside LE/LYSs from where it increases non-vesicular sterol exchange with other
      organelles.

PMID- 29580835
TI  - Implications of the Mediterranean diet and physical exercise on the lipid profile
      of metabolically healthy obese women as measured by nuclear magnetic resonance
      spectroscopy (1H NMR).
AB  - OBJECTIVE: There is a lack of consensus when it comes to establishing the
      biochemical parameters that define metabolically healthy obese (MHO) subjects.
      Indeed, most studies do not include subjects' lipid profiles. Our objective was
      to characterize lipoprotein size, particle and subclass concentration using 1H
      NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean
      diet and physical exercise. METHODS: 115 non-diabetic women (aged 35-55 years)
      with a body mass index (BMI) of 30-40 kg/m2 and <=1 of the following criteria:
      blood pressure >=135/85 mmHg, fasting plasma glucose >=100 mg/dL, HDL cholesterol
      <=50 mg/dL and triglycerides >=150 mg/dL were included. After two years of
      intensive lifestyle modification (Mediterranean diet and physical exercise), they
      were classified according to their weight loss: <5%, >=5%-<10% and >=10%.
      Lipoprotein size, particle and subclass concentrations were measured using 1H
      NMR. RESULTS: The final population, after dropouts, were 67 women (age: 44.5 +/-
      3.7 years, BMI: 36.3 +/- 4.7 kg/m2), of whom 23 (38.3%) lost <5%, and 22 (36.7%),
      lost >=5% to <10% and >=10% of baseline body weight, respectively. The lipid
      profile showed no significant changes after intervention, especially in small LDL
      particles or in production of HDL. The diameter of LDL and HDL particles did not
      change after two years of a Mediterranean diet and physical exercise. CONCLUSION:
      These results indicate that intensive lifestyle modification does not produce
      significant changes in the lipid profile of MHO women. Levels of more atherogenic
      or atheroprotective particles did not change after two years, despite the
      intervention.

PMID- 29580836
TI  - Differential expression of two Piwil orthologs during embryonic and gonadal
      development in pufferfish, Takifugu fasciatus.
AB  - Piwil was an important regulator gene in germ cell division during gonadal
      development. Two Piwi-like genes, Piwil1 and Piwil2, were first cloned from T.
      fasciatus. The full-length cDNAs of Piwil1 and Piwil2 were of 2933 and 3394 bp,
      respectively. Piwil1 and Piwil2 possessed an open reading frame (ORF) of 2565 and
      3138 bp, encoding 854 and 1045 amino acids, respectively. The tissue distribution
      analysis demonstrated that Piwil1 and Piwil2 were expressed at higher levels in
      gonad compared to other tissues (brain, liver, gill, etc.). The time-course
      dynamic expressions of Piwils during embryonic indicated that Piwil1 and Piwil2
      were mainly enriched in the early embryonic development. In testis, the
      expression of Piwil1 and Piwil2 increased at first but then decreased at mRNA and
      protein levels. However, the expression of Piwil1 and Piwil2 in the ovary showed
      a downward trend from the beginning. In addition, the expression levels of Piwil1
      and Piwil2 were weak in mature testes or ovaries. The immunohistochemistry
      analysis revealed that Piwil1 and Piwil2 were abundantly expressed in cytoplasm
      of spermatogonia, spermatocytes, oocyte I and oocytes II, which were mainly
      presented in the early stages of gonadal development. Our results suggested that
      Piwil was related to the differentiation of germ cells, and might play an
      important role in embryonic development. Therefore, our findings provided
      valuable information of Piwils in the reproductive cycle of T. fasciatus.

PMID- 29580837
TI  - Identification and characterization of two distinct sigma-class glutathione-S
      transferase from freshwater bivalve Cristaria plicata.
AB  - Glutathione-S-transferases (GSTs) are multifunctional phase II detoxification
      enzymes that catalyze the attachment of electrophilic substrates to glutathione,
      and play an important role in protecting organisms against the toxicity of
      reactive oxygen species. In this study, two distinct sigma-class GST (CpGSTsigma1
      and 2) cDNA sequences were cloned from freshwater bivalve Cristaria plicata. The
      full length cDNA of CpGSTsigma1 and 2 was 826 bp and 1609 bp, which encoded 213
      and 248 amino acid residues, respectively. Their transcripts were expressed in
      all detected tissues and the highest expression level was in hepatopancreas from
      C. plicata. The expression level of CpGSTsigma1 and 2 in hepatopancreas and
      hemocytes showed a significantly increased trend after bacterial challenge. The
      recombinant CpGSTsigma1 was successfully expressed as a soluble form in
      Escherichia coli DE3. The specific activity of recombinase toward CDNB was 46.965
      +/- 0.082 MUmol/min/mg, and its optimum temperature and pH was 37  degrees C and
      9.0, respectively. The recombinant of CpGSTsigma1 could bear 6 M urea and 8% SDS,
      when the concentration of urea was 8 M and its activity was only below 20%. The
      results might provide a better perspective on the mechanisms of resistance to
      bacterial infection in molluscs.

PMID- 29580838
TI  - Tackling mortality due to childhood tuberculosis.

PMID- 29580839
TI  - The now and then of gut-brain signaling.
AB  - Since their very beginnings, animals had gut sensory epithelial cells. In one of
      the first multicellular animals, Trichoplax - a literal wandering gut - food
      sensing and feeding was coordinated by specialized ventral sensor cells. In
      mammals, including humans, gut epithelial sensor cells (a.k.a enteroendocrine
      cells) have been recognized for an array of neuropeptides, like ghrelin and
      cholecystokinin, that modulate hunger or satiety. Indeed, since first described
      as "clear cells" by Rudfolf Heidenhain (1868), research efforts increasingly
      focused on their hormone neuropeptides leading to the alphabetical classification
      of one cell-one hormone (e.g. I-cell synthesizes only cholecystokinin). A recent
      explosion of molecular tools to study the biology of single cells is expanding
      the imagination of studies and unveiling intriguing aspects of gut sensory
      transduction. To mention a few: multimodal sensing, one cell expressing both
      ghrelin and cholecystokinin-the yin and yang of appetite-, and synapses with
      nerves. This brief account examines recent advances on gut sensory transduction
      to highlight how food and bacteria in the gut alter eating.

PMID- 29580840
TI  - HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway
      and Blocks Anti-viral ISG Induction.
AB  - Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to
      provide a cure. During infection Type 1 IFNs normally play an essential role in
      viral clearance, but in vivo IFN-alpha only has a modest impact on HIV-1
      infection, suggesting its possible targeting by HIV. Here, we report that the HIV
      protein, Vif, inhibits effective IFN-alpha signalling via degradation of
      essential JAK/STAT pathway components. We found that STAT1 and STAT3 are
      specifically reduced in HEK293T cells expressing Vif and that full length,
      infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent
      manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-alpha
      mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a
      functional consequence of this HIV-1-mediated immune evasion strategy.
      Interestingly, while total STAT levels were not reduced upon in vitro IIIB
      infection of primary human PBMCs, IFN-alpha-mediated phosphorylation of STAT1 and
      STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBDeltaVif),
      partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3
      expression and IFN-alpha-induced ISG15 were reduced in PBMCs from HIV-infected
      patients, compared to healthy controls. Furthermore, IFN-alpha pre-treatment of a
      CEM T lymphoblast cells significantly inhibited HIV infection/replication
      (measured by cellular p24), only in the absence of Vif (IIIBDeltaVif), but was
      unable to suppress full length IIIB infection. When analysing the mechanism by
      which Vif might target the JAK/STAT pathway, we found Vif interacts with both
      STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and
      MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin
      SOCS-box binding motif enables the formation of an active E3 ligase complex,
      which we found to be required for Vif's degradation of STAT1 and STAT3. In fact,
      the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be essential
      for Vif-mediated proteasomal degradation of STAT1 and STAT3. These results reveal
      a target for HIV-1-Vif and demonstrate how HIV-1 impairs the anti-viral activity
      of Type 1 IFNs, possibly explaining why both endogenous and therapeutic IFN-alpha
      fail to activate more effective control over HIV infection.

PMID- 29580841
TI  - Long Non-Coding RNAs Associated with Metabolic Traits in Human White Adipose
      Tissue.
AB  - Long non-coding RNAs (lncRNAs) belong to a recently discovered class of molecules
      proposed to regulate various cellular processes. Here, we systematically analyzed
      their expression in human subcutaneous white adipose tissue (WAT) and found that
      a limited set was differentially expressed in obesity and/or the insulin
      resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related
      lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both
      obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by
      antisense oligonucleotides in in vitro differentiated human adipocytes revealed
      that both genes regulated adipogenesis, lipid mobilization and adiponectin
      secretion. The observed effects could be attributed to crosstalk between ASMERs
      and genes within the master regulatory pathways for adipocyte function including
      PPARG and INSR. Altogether, our data demonstrate that lncRNAs are modulators of
      the metabolic and secretory functions in human fat cells and provide an emerging
      link between WAT and common metabolic conditions.

PMID- 29580843
TI  - In-clinic secondary tracheoesophageal puncture and voice prosthesis placement in
      laryngectomees.
AB  - Secondary tracheoesophageal puncture (TEP) with voice prosthesis placement
      represents one of the possibility to restore vocal function after total
      laryngectomy. However, some patients have comorbidities that contraindicate
      general anesthesia. In our department, an in-clinic TEP procedure for retrograde
      voice prosthesis placement was developed. It allows the immediate placement of
      the prosthesis and the avoidance of the use of dilators. We described our
      technique with advantages and pitfalls. The Provox Vega Puncture Set was used.
      Our technique for in-clinic secondary TEP without general anesthesia or target
      controlled infusion was a safe and effective procedure. It allows the use of the
      traditional TEP set, with possibility of voice prosthesis placement after
      previous TEP closure.

PMID- 29580842
TI  - MARCKSL1 Regulates Spine Formation in the Amygdala and Controls the Hypothalamic
      Pituitary-Adrenal Axis and Anxiety-Like Behaviors.
AB  - Abnormalities in limbic neural circuits have been implicated in the onset of
      anxiety disorders. However, the molecular pathogenesis underlying anxiety
      disorders remains poorly elucidated. Here, we demonstrate that myristoylated
      alanine-rich C-kinase substrate like 1 (MARCKSL1) regulates amygdala circuitry to
      control the activity of the hypothalamic-pituitary-adrenal (HPA) axis, as well as
      induces anxiety-like behaviors in mice. MARCKSL1 expression was predominantly
      localized in the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala
      of the adult mouse brain. MARCKSL1 transgenic (Tg) mice exhibited anxiety-like
      behaviors dependent on corticotropin-releasing hormone. MARCKSL1 increased spine
      formation in the central amygdala, and downregulation of MARCKSL1 in the amygdala
      normalized both increased HPA axis activity and elevated anxiety-like behaviors
      in Tg mice. Furthermore, MARCKSL1 expression was increased in the PFC and
      amygdala in a brain injury model associated with anxiety-like behaviors. Our
      findings suggest that MARCKSL1 expression in the amygdala plays an important role
      in anxiety-like behaviors.

PMID- 29580844
TI  - Primary Maxillary Deficiency Dentofacial Deformities: Occlusion and Facial
      Esthetic Surgical Outcomes.
AB  - PURPOSE: The purpose of this study was to document the malocclusion and facial
      dysmorphology in patients with primary maxillary deficiency (PMD) and chronic
      obstructive nasal breathing before treatment and the outcomes after bimaxillary
      orthognathic, genioplasty, and intranasal surgery. MATERIALS AND METHODS: A
      retrospective cohort study of patients with PMD undergoing bimaxillary
      orthognathic, chin, and intranasal surgery was implemented. The predictor
      variables were grouped into demographic, anatomic, operative, and longitudinal
      follow-up categories. The primary outcome variables were the initial
      postoperative occlusion achieved (T2; 5 weeks postoperatively) and that
      maintained long-term (T3 or T4; >2 years after surgery). Six occlusion parameters
      were assessed: overjet, overbite, coincidence of dental midlines, Angle
      classification, and molar vertical and transverse positions. A second outcome
      variable was facial esthetic results. Photographs were analyzed to document 7
      facial contour characteristics. RESULTS: Sixty-six patients met the inclusion
      criteria. Age at operation averaged 22 years (15 to 55 yr). The study included 18
      women (27%). Most patients (57 of 66; 86%) achieved and maintained a favorable
      occlusion for each parameter studied long-term (mean, 5 yr). The need for a 3
      segment Le Fort I was strongly associated with long-term posterior malocclusion.
      Facial dysmorphology before surgery included the appearance of a prominent chin
      (56%), flat labiomental fold (61%), prominent lower lip (88%), prominent nose
      (77%), sunken midface (100%), flat cheekbones (82%), and recessed upper lip
      (73%). Before surgery, 82% of patients exhibited at least 5 of the 7 key facial
      contour deformities. Correction of all 7 facial contour deformities was confirmed
      in 92% of patients in the long-term. In 8% of patients, an overly prominent
      appearing chin persisted. CONCLUSION: Using orthognathic techniques, most
      patients with PMD achieved and maintained a corrected occlusion long-term. In
      unoperated patients, a "facial esthetic type" was identified. Bimaxillary
      orthognathic and chin surgery proved effective in correcting associated facial
      dysmorphology in most patients.

PMID- 29580845
TI  - Occupational exposure and asthma.

PMID- 29580846
TI  - Barriers to medication adherence in asthma: The importance of culture and
      context.
AB  - OBJECTIVE: Significant disparities exist in asthma outcomes. Racial and ethnic
      minorities have lower controller medication adherence, which may contribute to
      differences in asthma morbidity between minority and non-minority groups. The
      objective of this review is to identify individual, patient-provider
      communication, and systems issues that contribute to this pattern of medication
      underuse and to discuss potential strategies for intervention. DATA SOURCES: Data
      were gathered from numerous sources, including reports of pharmacy and medical
      records, observational studies, and trials. STUDY SELECTIONS: Studies analyzed
      factors contributing to patterns of asthma medication adherence that differ by
      race and ethnicity. RESULTS: There is clear evidence of underuse of asthma
      controller medications among racial and ethnic minorities in prescription
      receipt, prescription initiation, and medication use once obtained. Individual
      factors such as medication beliefs and depressive symptoms play a role. Provider
      communication is also relevant, including limited discussion of complementary and
      alternative medicine use, difficulties communicating with patients and caregivers
      with limited English proficiency, and implicit biases regarding cultural
      differences. Systems issues (eg, insurance status, cost) and social context
      factors (eg, exposure to violence) also present challenges. Culturally informed
      strategies that capitalize on patient strengths and training providers in
      culturally informed communication strategies hold promise as intervention
      approaches. CONCLUSION: Disparities in controller medication use are pervasive.
      Identifying the sources of these disparities is a critical step toward generating
      intervention approaches to enhance disease management among the groups that bear
      the greatest asthma burden.

PMID- 29580847
TI  - Parabens and measures of adiposity among adults and children from the U.S.
      general population: NHANES 2007-2014.
AB  - BACKGROUND: Emerging experimental studies suggest that parabens could affect
      metabolism by altering the microbiome or signaling pathways involved in adipocyte
      differentiation. While human exposure to parabens is widespread, epidemiologic
      studies assessing the role of these chemicals on adiposity measures are scarce.
      OBJECTIVE: We examined associations of parabens with adiposity measures among
      adults and children in the U.S. general population. METHODS: We conducted
      covariate-adjusted linear and logistic regression models to examine associations
      between urinary biomarker concentrations of four parabens (butyl-BP, ethyl-EP,
      methyl-MP, and propyl paraben-PP) and measures of adiposity (obesity; body mass
      index, BMI or BMI z-score; and waist circumference) among 4730 adults (2007-2014)
      and 1324 children (2007-2012), participating in the National Health and Nutrition
      Examination Survey. We also assessed heterogeneity of associations by gender.
      RESULTS: We generally observed significant inverse associations between adiposity
      measures and paraben biomarker concentrations among adults (BP, EP, MP, PP) and
      children (MP). For example, adjusted prevalence odds ratios (95% confidence
      intervals, CI) for obesity per a ten-fold increase in MP concentrations were 0.64
      (95% CI: 0.55, 0.73) for adults and 0.71(95% CI: 0.52, 0.95) for children.
      Strength of inverse associations typically increased monotonically with
      increasing paraben exposure quartiles; and, in general, inverse associations were
      more pronounced among females. Associations remained when controlling for other
      phenolic compounds previously linked with adiposity measures. CONCLUSIONS: In
      this cross-sectional study of adiposity measures and parabens, we observed
      consistent inverse associations in a representative sample of U.S adults and
      children. Further studies are warranted to confirm our findings, examine the
      potential role of paraben sequestration in adipose tissue, and elucidate
      mechanisms by which parabens could alter metabolism.

PMID- 29580848
TI  - Human biomonitoring reference values for some non-persistent chemicals in blood
      and urine derived from the Canadian Health Measures Survey 2009-2013.
AB  - The Canadian Health Measures Survey collects nationally representative human
      biomonitoring data on a suite of chemicals and their metabolites, including many
      non-persistent chemicals. Data has been collected on non-persistent chemicals,
      including acrylamide, chlorophenols, environmental phenols and triclocarban,
      organophosphate insecticides, phthalates, polycyclic aromatic hydrocarbon,
      pyrethroid insecticides, and volatile organic compounds from 2009 to 2013. Using
      a systematic approach building on the reference interval concept proposed by the
      International Federation of Clinical Chemistry and Laboratory Medicine and the
      International Union of Pure and Applied Chemistry, we derive human biomonitoring
      reference values (RV95s) for these classes of non-persistent chemicals in blood
      and urine for the general Canadian population. RV95s were derived for biomarkers
      of non-persistent chemicals with widespread detection in Canadians (>66%
      detection rate). Samples with urinary creatinine levels outside the recommended
      range of 0.3-3.0 MUg/L were excluded. Reference populations were constructed by
      applying smoking and fasting as exclusion criteria where appropriate. Age and sex
      were evaluated as possible partitioning criteria and separate RV95s were derived
      for sub-populations in cases where partitioning was deemed necessary. Reference
      values were derived for 40 biomarkers and represent the first set of RV95s for
      non-persistent chemicals in the general Canadian population. These values provide
      a measure of the upper margin of background exposure in the general population
      and can be compared against individual and population human biomonitoring data.
      RV95s can be used to by public health officials to identify individuals with high
      exposures, and by risk assessors and risk managers to identify atypical exposures
      or subpopulations with elevated exposures.

PMID- 29580850
TI  - Selective binding and controlled release of anticancer drugs by polyanionic
      cyclodextrins.
AB  - The binding stoichiometry, binding constants, and inclusion mode of some water
      soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3
      sulfanylpropanoic acid)]-beta-cyclodextrin(H1), heptakis-[6-deoxy-6-(2
      sulfanylacetic acid)]-beta-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic
      acid)]-beta-cyclodextrin (H3) and mono-[6-deoxy-6-(2-sulfanylacetic acid)]-beta
      cyclodextrin (H4), with three anticancer drugs, i.e. irinotecan hydrochloride;
      topotecan hydrochloride; doxorubicin hydrochloride, were investigated by means of
      1H NMR, UV-Vis spectroscopy, mass spectra and 2D NMR. Polyanionic cyclodextrins
      H1-H2 showed the significantly high binding abilities of up to 2.6 * 104-2.0 *
      105 M-1 towards the selected anticancer drugs, which were nearly 50-1000 times
      higher than the corresponding Ks values of native beta-cyclodextrin. In addition,
      these polyanionic cyclodextrins also showed the pH-controlled release behaviors.
      That is, the anticancer drugs could be efficiently encapsulated in the
      cyclodextrin cavity at a pH value similar to that of serum but sufficiently
      released at an endosomal pH value of a cancer cell, which would make these
      cyclodextrin derivatives the potential carriers for anticancer drugs.

PMID- 29580849
TI  - Synthesis and biological evaluation of aminothiazoles against Histoplasma
      capsulatum and Cryptococcus neoformans.
AB  - The design and synthesis of a library of forty novel 2-aminoazole analogues as
      well as their evaluation as antifungal compounds against Histoplasma capsulatum
      and Cryptococcus neoformans is described. These structures were derived from N-[5
      (1-naphthalenylmethyl)-2-thiazolyl]cyclohexanecarboxamide (41F5), a fungistatic
      agent previously identified through phenotypic screening (Antimicrob Agents
      Chemother. 2013;57:4349). Modifications to improve potency and water-solubility
      of 41F5 focused primarily on the 5-naphthalenyl group, the thiazole core, and the
      methylene linker between these two structural elements. In general, compounds
      with lipophilic [5+6] bicyclic ring systems, such as the 7-benzothiophenyl- and 4
      indanyl groups, at the 5-position were 2-3 times more active against both fungal
      species as compared to 41F5. Also, introduction of a carbonyl group at the
      methylene linker of 41F5 resulted in a 2-3-fold increase in potency. These highly
      active compounds also showed generally low toxicities against murine P388D1
      macrophages resulting in selectivity indices ranging from 63 to >200. Compounds
      that were highly active against fluconazole-sensitive C. neoformans strains had
      almost identical activity against fluconazole-resistant variants of this fungus
      indicating that 14alpha-demethylase is not their molecular target. Highly active
      compounds also retained activity against H. capsulatum phagocytosed into P388D1
      macrophages.

PMID- 29580851
TI  - Structure-activity relationships of succinimidyl-Cys-C(O)-Glu derivatives with
      different near-infrared fluorophores as optical imaging probes for prostate
      specific membrane antigen.
AB  - Prostate-specific membrane antigen (PSMA), which is overexpressed in malignant
      prostate cancer (PCa), is an ideal target for imaging and therapy of PCa. We
      previously reported a PSMA imaging probe, 800CW-SCE, based on succinimidyl-Cys
      C(O)-Glu (SCE) for optical imaging of PCa. In this study, we investigated the
      structure-activity relationships of novel SCE derivatives with five different
      near-infrared (NIR) fluorophores (IRDye 680LT, IRDye 750, Indocyanine Green,
      Cyanine 5.5, and Cyanine 7) as optical imaging probes targeting PSMA. An in vitro
      binding assay revealed that 800CW-SCE, 680LT-SCE, and 750-SCE exhibited higher
      binding affinity than 2-PMPA, which is known as a PSMA inhibitor. These three SCE
      derivatives were internalized into PSMA-positive cells (LNCaP cells) but not into
      PSMA-negative cells (PC-3 cells). In the in vivo imaging study, 800CW-SCE and 750
      SCE were highly accumulated in LNCaP tumors but not in PC-3 tumors, and the ratio
      of LNCaP/PC-3 accumulation of 800CW-SCE was higher than that of 750-SCE. The
      present study may provide valuable molecular design information for the future
      development of new PSMA imaging probes based on the SCE scaffold.

PMID- 29580852
TI  - Modelling low pathogenic avian influenza introduction into the commercial poultry
      industry.
AB  - Outbreaks of highly pathogenic avian influenza (HPAI) in commercial poultry
      flocks are rare but highly disruptive to the industry. There is evidence that low
      pathogenic avian influenza (LPAI) can transfer from wild birds to domestic
      flocks, where it may mutate to HPAI, and the industry is concerned that an
      increasing demand for free-range produce may affect the risk of LPAI and HPAI
      outbreaks. In this paper we focus on LPAI introduction and establishment, and
      formulate a branching process model to compare risk between sectors and their
      contribution to overall industry-level risk. Our aim is to determine how
      heterogeneity in avian influenza viruses and the distinct population structures
      of each sector - caged, barn and free-range, meat and layer - interact with a
      continuous risk of virus introduction to affect outbreak probabilities. We show
      that free-range access is the most influential driver of LPAI outbreaks, with
      production cycle length having relatively little effect. We demonstrate that
      variation in virus transmission rates is particularly important when modelling
      avian influenza introduction to domestic poultry. Virus-free status is of
      interest for biosecurity and we distinguish how it differs from the usual
      probability of extinction, and discuss how production cycle length affects this
      difference. We also use the nonlinear relationship between shed size and risk to
      identify conditions for which shed size is most influential.

PMID- 29580853
TI  - FEM simulation of EM field effect on body tissues with bio-nanofluid (blood with
      nanoparticles) for nanoparticle mediated hyperthermia.
AB  - The study of temperature profiles and heat transport within the human body when
      subjected to electromagnetic waves is crucial for development and improvement of
      radiofrequency hyperthermia treatments. These treatments being minimally invasive
      can be a better alternative over surgery and chemotherapy for treatment of
      cancer. Nanoparticle-mediated hyperthermia for cancer therapy is a growing area
      of cancer nanomedicine because of the potential for localized and targeted
      destruction of cancer cells. This treatment is dependent on many factors,
      including thermal conductivity of bio-nanofluid, volume fraction of
      nanoparticles,excitation wavelength and power and metabolic heat generation. The
      present study employs Finite Element Method to investigate and optimize the
      effects of these parameters on temperature distributions and discuss the heat
      transport within the human body injected with nanoparticles and subjected to
      electromagnetic waves. The LTNE (Local Thermal Non Equilibrium) model is used to
      characterize the bioheat transport through the biological medium. In order to
      understand the effects induced by imposed electromagnetic field, the specific
      absorption rate (SAR) of body tissues is also studied. The results obtained have
      been validated against the pertinent numerical results in the literature. This
      study provides benchmark numerical solutions for heat transport through
      biological media thereby, helping in understanding the thermophysiologic response
      of bio-nanofluid towards imposed electromagnetic radiation.

PMID- 29580854
TI  - Metabolomics-based evidence of the hypoglycemic effect of Ge-Gen-Jiao-Tai-Wan in
      type 2 diabetic rats via UHPLC-QTOF/MS analysis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from
      traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata
      (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang
      Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment
      of diabetes in China, reflecting the potent hypoglycemic effect of its
      ingredients. However, little is known of the hypoglycemic effect of GGJTW and the
      underlying metabolic mechanism. AIM OF THE STUDY: This study aimed to investigate
      the hypoglycemic effect of GGJTW in type 2 diabetic rats and the metabolic
      mechanism of action. MATERIALS AND METHODS: Ultra high-performance liquid
      chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry
      (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring
      hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ),
      and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels,
      body weight, and biochemical parameters, including lipid levels, hepatic-renal
      function, and hepatic histopathology were used to confirm the hyperglycaemic
      toxicity and attenuation effects. An orthogonal partial least squared
      discriminant analysis (OPLS-DA) approach highlighted significant differences in
      the metabolome of the healthy control, diabetic, and drug-treated rats. The
      metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes
      (KEGG) database were used to investigate the underlying metabolic pathways.
      RESULTS: Metabolic profiling revealed 37 metabolites as the most potential
      biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of
      the metabolites were primarily associated with bile acid metabolism and lipid
      metabolism. The most critical pathway was primary bile acid biosynthesis pathway
      involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic
      acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA),
      taurochenodesoxycholic acid (TCDCA), and taurine. CONCLUSIONS: The significantly
      altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabetic
      rats and the underlying metabolic mechanism. This study will be meaningful for
      the clinical application of GGJTW and valuable for further exploration of the
      mechanism.

PMID- 29580855
TI  - Statin therapy is associated with higher long-term but not perioperative survival
      after abdominal aortic aneurysm repair.
AB  - BACKGROUND: Although preoperative and perioperative statin therapy improves
      postoperative outcomes in several populations, few data examine its association
      with survival after abdominal aortic aneurysm (AAA) repair. In addition, no data
      exist regarding the benefits of starting statins in patients with AAA not
      currently taking them. METHODS: We performed a registry-based study of all
      patients undergoing repair of AAAs in the Vascular Quality Initiative between
      2003 and 2017 without documented statin intolerance. In our primary analysis, we
      evaluated the association between preoperative statin therapy and long-term
      mortality, 30-day mortality, and in-hospital myocardial infarction and stroke. As
      a secondary analysis, we studied the cohort of patients not taking a statin
      preoperatively and compared their long-term mortality on the basis of whether
      they were discharged on a statin. To account for nonrandom assignment to
      treatment, we constructed propensity scores and applied inverse probability
      weighting. RESULTS: We identified 40,452 AAA repairs, of which 37,950 fit our
      entry criteria (29,257 endovascular and 8693 open). Overall, 25,997 patients
      (69%) were taking a statin preoperatively, with patients undergoing endovascular
      aneurysm repair more frequently taking a statin than those undergoing open repair
      (69% compared with 66%; P < .001). After propensity weighting, preoperative
      statin therapy was not associated with 30-day death or in-hospital stroke or
      myocardial infarction. However, patients taking statins preoperatively
      experienced higher adjusted 1-year (94% vs 90%) and 5-year (85% vs 81%) survival
      from the date of surgery compared with those who were not (P < .001 overall),
      although subgroup analysis showed that this applied only to intact or symptomatic
      aneurysms. Of the 11,941 patients not taking a statin preoperatively and
      discharged alive, 2910 (24%) started on a statin before discharge. In our
      secondary analysis of the subset of patients not taking statins preoperatively,
      those initiated on a statin before discharge experienced higher survival at 1
      year (94% vs 91%) and 5 years (89% vs 81%; P < .001 overall) than those who
      remained off statin therapy, with the greatest absolute long-term survival
      difference in patients with rupture (87% vs 62%; P < .001 overall). CONCLUSIONS:
      Preoperative statin therapy is associated with higher long-term survival but not
      perioperative mortality and morbidity in patients undergoing AAA repair, and
      initiating statin therapy in previously statin-naive patients is associated with
      markedly higher survival. All patients with AAAs without contraindications should
      receive statin therapy. In patients not taking a statin at the time of AAA
      repair, clinicians should consider initiating one before discharge.

PMID- 29580856
TI  - Induction of inosine triphosphatase activity during ribavirin treatment for
      chronic hepatitis C.
AB  - BACKGROUND: Ribavirin (RBV) is an antiviral agent and the primary component for
      chronic hepatitis C (CHC) therapy. Hemolytic anemia is limitation for RBV
      treatment. Inosine triphosphatase (ITPA) activity has been associated with
      severity of RBV-induced anemia. However, changes in ITPA activity during CHC
      therapy are unknown. The aim of this study was to measure the time-dependent
      change in ITPA activity over the RBV treatment. METHODS: Forty-two patients with
      CHC were evaluated for ITPA activity over the course of RBV treatment. RESULTS:
      The median value of ITPA activity at start of RBV treatment was 134.2 MUmol/h/g
      hemoglobin (Hb; range, 26.3-251.0 MUmol/h/g Hb). The ITPA activity values at 4,
      8, and 12 weeks during RBV treatment were 143.2, 202.2, and 225.7 MUmol/h/g Hb,
      respectively, and these ITPA values were significantly elevated compared with the
      start of treatment (p < 0.001). In patients with ITPA variants, patients with
      anemia (Hb < 10 g/dL) had greater elevated ITPA activities compared with patients
      without anemia at 12 weeks. CONCLUSION: Our findings indicate that ITPA
      activities are elevated with RBV therapy, and this elevation may be a risk of
      anemia in late therapeutic phase in patients that began with low ITPA activity.

PMID- 29580857
TI  - Analytical interference of HBOC-201 (Hemopure, a synthetic hemoglobin-based
      oxygen carrier) on four common clinical chemistry platforms.
AB  - BACKGROUND: There are 13 million blood transfusions each year in the US.
      Limitations in the donor pool, storage capabilities, mass casualties, access in
      remote locations and reactivity of donors all limit the availability of
      transfusable blood products to patients. HBOC-201 (Hemopure(r)) is a second
      generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an
      "oxygen bridge" to maintain oxygen carrying capacity while transfusion products
      are unavailable. Hemopure presents the advantages of extended shelf life, ambient
      storage, and limited reactive potential, but its extracellular location can also
      cause significant interference in modern laboratory analyzers similar to severe
      hemolysis. METHODS: Observed error in 26 commonly measured analytes was
      determined on 4 different analytical platforms in plasma from a patient
      therapeutically transfused Hemopure as well as donor blood spiked with Hemopure
      at a level equivalent to the therapeutic loading dose (10% v/v). RESULTS:
      Significant negative error ratios >50% of the total allowable error (>0.5tAE)
      were reported in 23/104 assays (22.1%), positive bias of >0.5tAE in 26/104 assays
      (25.0%), and acceptable bias between -0.5tAE and 0.5tAE error ratio was reported
      in 44/104 (42.3%). Analysis failed in the presence of Hemopure in 11/104 (10.6%).
      Observed error is further subdivided by platform, wavelength, dilution and
      reaction method. CONCLUSION: Administration of Hemopure (or other hemoglobin
      based oxygen carriers) presents a challenge to laboratorians tasked with
      analyzing patient specimens. We provide laboratorians with a reference to
      evaluate patient samples, select optimal analytical platforms for specific
      analytes, and predict possible bias beyond the 4 analytical platforms included in
      this study.

PMID- 29580858
TI  - Analytical validation of an ultra low-cost mobile phone microplate reader for
      infectious disease testing.
AB  - Most mobile health (mHealth) diagnostic devices for laboratory tests only analyze
      one sample at a time, which is not suitable for large volume serology testing,
      especially in low-resource settings with shortage of health professionals. In
      this study, we developed an ultra-low-cost clinically-accurate mobile phone
      microplate reader (mReader), and clinically validated this optical device for 12
      infectious disease tests. The mReader optically reads 96 samples on a microplate
      at one time. 771 de-identified patient samples were tested for 12 serology assays
      for bacterial/viral infections. The mReader and the clinical instrument blindly
      read and analyzed all tests in parallel. The analytical accuracy and the
      diagnostic performance of the mReader were evaluated across the clinical
      reportable categories by comparison with clinical laboratorial testing results.
      The mReader exhibited 97.59-99.90% analytical accuracy and <5% coefficient of
      variation (CV). The positive percent agreement (PPA) in all 12 tests achieved
      100%, negative percent agreement (NPA) was higher than 83% except for one test
      (42.86%), and overall percent agreement (OPA) ranged 89.33-100%. We envision the
      mReader can benefit underserved areas/populations and low-resource settings in
      rural clinics/hospitals at a low cost (~$50 USD) with clinical-level analytical
      quality. It has the potential to improve health access, speed up healthcare
      delivery, and reduce health disparities and education disparities by providing
      access to a low-cost spectrophotometer.

PMID- 29580860
TI  - Trichologic response of platelet-rich plasma in androgenetic alopecia is
      maintained during combination therapy.

PMID- 29580859
TI  - Stage IV melanoma of unknown primary: A population-based study in the United
      States from 1973 to 2014.
AB  - BACKGROUND: Melanoma of unknown primary (MUP) is incompletely described on a
      population level. OBJECTIVE: We sought to characterize stage IV MUP in a
      population-based cancer registry. METHODS: We developed a novel search algorithm
      to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End
      Results 18 registries from 1973 to 2014. Cases of stage IV melanoma of known
      primary (MKP) served as a comparison group. Age-standardized incidence rates,
      demographic characteristics, adjusted disease-specific survival, and Cox
      proportional hazard models were calculated for MUP and MKP. RESULTS: A total of
      322 stage IV MUP cases and 12,796 stage IV MKP cases were identified in
      Surveillance, Epidemiology, and End Results 18 registries from 1973 to 2014. The
      incidence of stage IV MUP is increasing, particularly for patients younger than
      30 years of age. In multivariate analyses, age older than 50 and a lack of
      surgical treatment were negative prognostic factors for stage IV MUP. Relative
      survival, but not 5-year adjusted disease-specific survival, was higher for stage
      IV MUP than for MKP. LIMITATIONS: Limitations include the retrospective study
      design and possible misclassification of MUP. CONCLUSIONS: The incidence of stage
      IV MUP is increasing, and stage IV MUP shares similar prognostic factors with
      stage IV MKP, including age and surgical treatment.

PMID- 29580861
TI  - Melanoma staging: Varying precision and terminal digit clustering in Breslow
      thickness data is evident in a population-based study.
AB  - BACKGROUND: Errors in Breslow thickness reporting can give misclassification of T
      category, an important classifier in melanoma staging. OBJECTIVE: We sought to
      investigate precision (number of digits) and terminal digit clustering in Breslow
      thickness and potential consequences for T category. METHODS: All first primary
      and morphologically verified invasive melanomas in Norway between 2008 and 2015
      were included. A smoothing model was fitted to estimate the underlying Breslow
      thickness distribution without digit clustering. RESULTS: Thickness was reported
      for 13,057 (97.5%) patients; the median was 1.0 mm (range, 0.09-85). It was
      reported as whole numbers (15.6%), to 1 decimal (78.2%) and 2 decimal places
      (6.2%)-thin tumors with more precision than thick tumors. Terminal digit
      clustering was found with marked peaks in the observed frequency distribution for
      terminal digits 0 and 5, and with drops around these peaks. Terminal digit
      clustering increased proportions of patients classified with T1 and T4 tumors and
      decreased proportions classified with T2 and T3. LIMITATIONS: Breslow thickness
      was not reported in 2.5% of cases. CONCLUSIONS: The Norwegian recommendation of
      measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was
      marked, with consequences for T category. Pathologists, clinicians, and
      epidemiologists should know that clustering of thickness data around T category
      cut points can impact melanoma staging with consequent effect on patient
      management and prognosis.

PMID- 29580862
TI  - Galactose metabolism and toxicity in Ustilago maydis.
AB  - In most organisms, galactose is metabolized via the Leloir pathway, which is
      conserved from bacteria to mammals. Utilization of galactose requires a close
      interplay of the metabolic enzymes, as misregulation or malfunction of individual
      components can lead to the accumulation of toxic intermediate compounds. For the
      phytopathogenic basidiomycete Ustilago maydis, galactose is toxic for wildtype
      strains, i.e. leads to growth repression despite the presence of favorable carbon
      sources as sucrose. The galactose sensitivity can be relieved by two independent
      modifications: (1) by disruption of Hxt1, which we identify as the major
      transporter for galactose, and (2) by a point mutation in the gene encoding the
      galactokinase Gal1, the first enzyme of the Leloir pathway. The mutation in
      gal1(Y67F) leads to reduced enzymatic activity of Gal1 and thus may limit the
      formation of putatively toxic galactose-1-phosphate. However, systematic
      deletions and double deletions of different genes involved in galactose
      metabolism point to a minor role of galactose-1-phosphate in galactose toxicity.
      Our results show that molecular triggers for galactose toxicity in U. maydis
      differ from yeast and mammals.

PMID- 29580863
TI  - Stromal progenitor cell modulation by thalidomide in the treatment of oral
      chronic graft-versus-host disease.

PMID- 29580864
TI  - Epstein-barr virus DNAemia monitoring for the management of post-transplant
      lymphoproliferative disorder.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a potentially
      fatal complication of allogeneic hematopoietic cell transplantation (HCT).
      Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the
      development of PTLD. METHODS: We retrospectively studied 306 patients monitored
      for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of
      the monitoring in the management of PTLD. DNAemia was monitored weekly for >=12
      weeks post-transplantation. RESULTS: Reactivation was detected in 82% of
      patients. PTLD occurred in 14% of the total patients (17% of patients with
      reactivation). PTLD was treated with rituximab only when and if the diagnosis was
      established. This allowed us to evaluate potential DNAemia thresholds for pre
      emptive therapy. We suggest 100,000-500,000 IU per mL whole blood as this would
      result in unnecessary rituximab administration to only 4-20% of patients and near
      zero mortality due to PTLD. After starting rituximab (for diagnosed PTLD),
      sustained regression of PTLD occurred in 25/25 (100%) patients in whom DNAemia
      became undetectable. PTLD progressed or relapsed in 12/17 (71%) patients in whom
      DNAemia was persistently detectable. DISCUSSION: In conclusion, for pre-emptive
      therapy of PTLD, we suggest threshold DNAemia of 100,000-500,000 IU/mL.
      Persistently detectable DNAemia after PTLD treatment with rituximab appears to
      have 71% positive predictive value and 100% negative predictive value for PTLD
      progression/relapse.

PMID- 29580865
TI  - Bone marrow-mesenchymal stromal cell infusion in patients with chronic kidney
      disease: A safety study with 18 months of follow-up.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a progressive loss of kidney function
      and structure that affects approximately 13% of the population worldwide. A
      recent meta-analysis revealed that cell-based therapies improve impaired renal
      function and structure in preclinical models of CKD. We assessed the safety and
      tolerability of bone marrow-mesenchymal stromal cell (MSC) infusion in patients
      with CKD. METHODS: A single-arm study was carried out at one center with 18-month
      follow-up in seven eligible patients with CKD due to different etiologies such as
      hypertension, nephrotic syndrome (NS) and unknown etiology. We administered an
      intravenous infusion (1-2 * 106 cells/kg) of autologous cultured MSCs. The
      primary endpoint was safety, which was measured by number and severity of adverse
      events. The secondary endpoint was decrease in the rate of decrease in estimated
      glomerular filtration rate (eGFR). We compared kidney function during the follow
      up visits to baseline and 18 months prior to the intervention. RESULTS: Follow-up
      visits of all seven patients were completed; however, we have not observed any
      cell-related adverse events during the trial. Changes in eGFR (P = 0.10) and
      serum creatinine (P = 0.24) from 18 months before cell infusion to baseline in
      comparison with baseline to 18 months were not statistically significant.
      CONCLUSIONS: We showed safety and tolerability of a single-dose infusion of
      autologous MSCs in patients with CKD.

PMID- 29580866
TI  - Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy
      of acute liver failure.
AB  - BACKGROUND & AIMS: Acute liver failure is a rapidly progressive deterioration of
      hepatic function resulting in high mortality and morbidity. Metabolic enzymes can
      translocate to the nucleus to regulate histone acetylation and gene expression.
      METHODS: Levels and activities of pyruvate dehydrogenase complex (PDHC) and
      lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice
      exposed to various hepatotoxins including CD95-antibody, alpha-amanitin, and
      acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in
      livers of mice with acute liver failure and analyzed by gene ontology enrichment
      analysis. Cell viability was evaluated in cell lines knocked-down for PDHA1 or
      LDH-A and in cells incubated with the LDH inhibitor galloflavin after treatment
      with CD95-antibody. We evaluated whether the histone acetyltransferase inhibitor
      garcinol or galloflavin could reduce liver damage in mice with acute liver
      failure. RESULTS: Levels and activities of PDHC and LDH were increased in nuclear
      fractions of livers of mice with acute liver failure. The increase of nuclear
      PDHC and LDH was associated with increased concentrations of acetyl-CoA and
      lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression
      in livers of mice with acute liver failure suggested that increased histone H3
      acetylation induces the expression of genes related to damage response. Reduced
      histone acetylation by the histone acetyltransferase inhibitor garcinol decreased
      liver damage and improved survival in mice with acute liver failure. Knock-down
      of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus.
      Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC,
      reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines
      in mice with acute liver failure. Mice treated with galloflavin also showed a
      dose-response increase in survival. CONCLUSION: PDHC and LDH translocate to the
      nucleus, leading to increased nuclear concentrations of acetyl-CoA and lactate.
      This results in histone H3 hyper-acetylation and expression of damage response
      genes. Inhibition of PDHC and LDH reduces liver damage and improves survival in
      mice with acute liver failure. Thus, PDHC and LDH are targets for therapy of
      acute liver failure. LAY SUMMARY: Acute liver failure is a rapidly progressive
      deterioration of liver function resulting in high mortality. In experimental
      mouse models of acute liver failure, we found that two metabolic enzymes, namely
      pyruvate dehydrogenase complex and lactic dehydrogenase, translocate to the
      nucleus resulting in detrimental gene expression. Treatment with an inhibitor of
      these two enzymes was found to reduce liver damage and to improve survival.

PMID- 29580867
TI  - Eosinophils Accelerate Pathogenesis of Psoriasis by Supporting an Inflammatory
      Milieu that Promotes Neutrophil Infiltration.
AB  - Eosinophils are proinflammatory granulocytes that are involved in the
      pathogenesis of various inflammatory reactions. However, their roles in psoriasis
      remain largely unknown. In this study, by examining the inflammatory features of
      the eosinophilic cell line EoL-1 and an imiquimod-induced murine model of
      psoriasis, we show that eosinophils provide inflammatory signals that accelerate
      the pathogenesis of psoriasis. EoL-1 cells constitutively expressed TLR7, which
      mediates acute and rapidly developing psoriatic inflammation. The activation of
      TLR7 on EoL-1 cells using R837 resulted in the secretion of inflammatory
      mediators that support the migration, activation, and survival of neutrophils.
      The underlying pathologic role of eosinophils in psoriatic inflammation was
      further substantiated by markedly decreased psoriasiform inflammation in
      imiquimod-treated DeltadblGATA mice, which have a systemic eosinophil deficiency.
      While imiquimod-treated wild-type mice showed a significant increase in the
      eosinophils in their skin, neutrophils remarkably outnumbered the eosinophils in
      the skin, lymph nodes, and spleen in wild-type mice after imiquimod application.
      In addition, lesional skin samples from psoriasis patients also showed up
      regulated eosinophil cytotoxic granules, accompanied by marked neutrophil
      infiltration. Based on these collective data, we propose that eosinophils
      accelerate psoriatic inflammation by supporting inflammatory microenvironments to
      favor the activation and infiltration of neutrophils.

PMID- 29580868
TI  - Downregulated TRPV1 Expression Contributes to Melanoma Growth via the Calcineurin
      ATF3-p53 Pathway.
AB  - Melanoma is the most lethal form of skin cancer with increasing incidence over
      the years. Because of its rapid proliferative and drastic metastatic capacity,
      the prognosis of melanoma remains dismal, although the targeted therapy and
      immunotherapy have gained revolutionary progress recently. Therefore, it is of
      necessity to further clarify the mechanism of melanoma pathogenesis for
      developing an alternative treatment strategy. Transient receptor potential
      vanilloid 1 (TRPV1) is a nonselective Ca2+ channel greatly involved in regulating
      cell apoptosis, proliferation, metabolism, and cancer development, but its role
      in melanoma remains unknown. Herein, we first found that TRPV1 expression was
      significantly decreased in melanoma tissues and cell lines, compared with nevus
      tissues and normal melanocytes, respectively. We then proved that TRPV1
      overexpression or its agonist capsaicin treatment inhibited melanoma growth by
      activating p53 and inducing cell apoptosis. A subsequent mechanistic study
      revealed that TRPV1 induced Ca2+ influx to regulate p53 activation via
      calcineurin-ATF3 transcriptional cascade. Finally, the effect of TRPV1 on
      melanoma growth was proved in vivo. Altogether, our study demonstrates that TRPV1
      is a potential tumor suppressor in melanoma.

PMID- 29580869
TI  - Inverse Relationship between Vitiligo-Related Genes and Skin Cancer Risk.

PMID- 29580870
TI  - Hyfraxins A and B, cytotoxic ergostane-type steroid and lanostane triterpenoid
      glycosides from the invasive ash dieback ascomycete Hymenoscyphus fraxineus.
AB  - A virulent culture of Hymenoscyphus fraxineus, the causal agent of ash dieback,
      was investigated for its production of secondary metabolites in a 70 L batch
      fermentation. Chemical analysis of the mycelial extract by means of flash
      chromatography and preparative HPLC led to the isolation of a new ergostane-type
      steroid (1) and a new related lanostane triterpenoid (2), both revealing the same
      glycosylation pattern. While their planar structures were elucidated by HR-ESIMS
      and NMR data, relative stereochemistry was assigned by ROESY correlations in
      conjunction with H,H and C,H coupling constants. Absolute configuration was
      determined based on ROESY correlations between the aglycons and the sugar
      moieties, which were identified in both cases as d-mannose by GC/MS analysis of
      the trimethylsilylated derivatives. The isolated compounds, for which we propose
      the trivial names hyfraxins A (1) and B (2), were found to be cytotoxic against
      the mouse fibroblast cell line L929 and exhibited moderate to weak activity
      against Gram-positive bacteria.

PMID- 29580872
TI  - Molecular and culture based assessment of bacterial pathogens in subjects with
      diabetic foot ulcer.
AB  - INTRODUCTION: Expeditious and precise discerning of bacterial pathogens is a
      fundamental grail, of clinical diagnostic microbiology. Genotypic detection is a
      budding substitute to recognize phenotypic culture based processes in bacterial
      identification. AIMS: We report a comparative evaluation of biochemical and
      genomic-based assays for exploring the commonest bacterial flora of infected
      diabetic foot ulcers along with clinical variables of subjects enrolled. METHODS:
      The pathogens selected (i) Staphylococcus aureus ii) Pseudomonas aeruginosa, iii)
      Escherichia coli and iv) Klebsiella pneumonia, stood for the most frequent
      isolates of diabetic foot infection in previous studies from Northern India.
      Identification of these pathogens were done by conventional assays and polymerase
      chain reaction. RESULTS: Of 50 specimens obtained from infected DFUs, 74% of
      cases were affirmative by bacteriological assays and 90% showed positivity via
      polymerase chain reaction (PCR). Among processed samples 44 isolates were
      detectable through phenotypic analysis and 65 bacteria by species-specific PCR.
      Thirteen samples and 21 isolates could not be scrutinized by phenotypic
      identification systems. The most prevalent pathogens identifiable were Klebsiella
      pneumonia, followed by Staphylococcus aureus, Pseudomonas aeruginosa, and
      Escherichia coli. CONCLUSIONS: We have shown that PCR-based diagnostic methods
      improved the identification compared to conventional methods and highlight the
      incorporation of PCR due to shorten turnaround time translating into improved
      clinical outcomes.

PMID- 29580871
TI  - Effect of oral vitamin D supplementation on glycemic control in patients with
      type 2 diabetes mellitus with coexisting hypovitaminosis D: A parellel group
      placebo controlled randomized controlled pilot study.
AB  - CONTEXT: Vitamin D supplementation in type 2 diabetes mellitus patients may lead
      to improved glycemic control by improving insulin secretion and decreasing
      insulin resistance. AIMS: To investigate effect of oral vitamin D supplementation
      on glycemic control, in patients with type 2 diabetes mellitus and coexisting
      hypovitaminosis D. SETTINGS AND DESIGN: Randomized, Parallel Group, Placebo
      Controlled Trial carried out in a tertiary care hospital of Indian Armed Forces.
      METHODS AND MATERIAL: Sixty patients with coexisting type 2 diabetes mellitus and
      hypovitaminosis D were randomized into cases and controls and were supplemented
      with oral Vitamin D and microcrystalline cellulose respectively for six months.
      Subjects' HbA1c and vitamin D levels were monitored at the beginning and end of
      the study, fasting plasma glucose (FPG) & post prandial plasma glucose (PPPG)
      during monthly OPD visits. STATISTICAL ANALYSIS USED: Intra-group comparison was
      made by paired t test & unpaired t test was used for inter-group (A v/s B)
      comparisons. Repeated measures ANOVA was undertaken to compare values over time.
      RESULTS: The two groups were comparable for all parameters at baseline. Case
      group showed significant decrease in mean HbA1c levels (7.29% to 7.02%; P =
      0.01), mean FPG levels (131.4 to 102.6 mg/dl; P = 0.04) and mean PPPG levels
      (196.2 to 135.0 mg/dl; P < 0.001). Incidentally, significant improvement in
      systolic as well as diastolic blood pressure and total cholesterol was also noted
      in the cases, while for LDL cholesterol improvement tended towards significance
      (p = 0.05). CONCLUSIONS: We found that oral vitamin D supplementation was
      associated with improved glycemic control and other metabolic parameters in
      patients with type 2 diabetes mellitus. Supplementation to achieve normal levels
      of vitamin D can be a promising adjuvant therapy for T2DM patients & coexisting
      hypovitaminosis D.

PMID- 29580873
TI  - Reproductive Endocrinology: Novel Insights into Pathophysiology and Clinical
      Management.

PMID- 29580875
TI  - A Leadership Taxonomy for Clinical Dietetics Practice.

PMID- 29580874
TI  - Comparison of the Dietary Antioxidant Profiles of 21 a priori Defined
      Mediterranean Diet Indexes.
AB  - BACKGROUND: The Mediterranean Diet (MD) is a dietary pattern that features a high
      quotient of antioxidant-rich foods. Differences in the level of dietary
      antioxidants intake reflected by different MD indexes has received little
      research attention. OBJECTIVE: The purpose of this study was to compare the
      dietary antioxidant profile of 21 a priori defined indexes of adherence to the
      MD. DESIGN: A cross-sectional study. PARTICIPANTS/SETTING: A total of 14,756
      participants belonging to two Spanish European Prospective Investigation into
      Cancer and Nutrition cohorts, aged 32 to 69 years, recruited between 1992 and
      1996, were included. MAIN OUTCOME MEASURE: Participants provided information on
      diet through a validated diet history questionnaire. Antioxidants (vitamin C,
      beta carotene and alpha-tocopherol), total antioxidant capacity, total
      polyphenols, flavonoids, and polyphenol antioxidant content score were estimated
      using different food composition databases. Twenty-one MD indexes were
      operationalized. STATISTICAL ANALYSIS: Spearman correlation coefficients between
      the indexes were calculated and hierarchical clustering was applied to identify
      cluster groups. Weighted kappa statistic was estimated to value the scoring
      agreements between indexes. Antioxidant profiles between the MD indexes were
      compared based on geometric mean intakes. The relationship between each MD index
      with the components of the antioxidant profile was evaluated using linear
      multivariable regression analysis. RESULTS: Correlation patterns between the MD
      indexes showed that about half of the indexes were moderately-to-weakly
      correlated with each other (rho<0.5). The main cluster groups derived denoted the
      high-, moderate-, and low-correlated MD indexes. Three MD indexes (MD pattern
      2002, Prevention with MD, and Alternate MD index) presented the highest mean
      intakes of antioxidant vitamins, total antioxidant capacity, total polyphenols,
      flavonoids, and polyphenol antioxidant content score. These and other indexes
      (mainly those belonging to the MD Scale group) captured higher intake levels of
      dietary antioxidants overall. CONCLUSIONS: The level of dietary antioxidant
      intake that is captured through the different MD indexes differed due to the
      variation in their construction. Study results also suggest that some MD indexes
      reflect a higher antioxidant profile.

PMID- 29580876
TI  - Regulatory respiratory data refinement with reduced animal usage.
AB  - INTRODUCTION: Assessment of effects of potential drug candidates on the
      respiratory system is part of the regulatory preclinical safety assessment
      conducted prior to first in human trials (FTIH). Commonly, this is carried out
      utilizing head out plethysmography (HOP) or whole body plethysmography (WBP)
      which record only ventilatory parameters. When dosing via the inhaled route a
      more thorough respiratory assessment, including a direct measure of airway
      mechanics, is desirable. The aim of the present work was to improve the strategy
      for respiratory safety testing by a) evaluating a telemetered pleural pressure -
      HOP (PP-HOP) model and b) evaluating a crossover study design protocol in the WBP
      model to reduce variability and animal usage. METHODS: For the PP- HOP model,
      rats were surgically implanted with a telemetry device for measurement of pleural
      pressure. Animals were placed in HOP tubes and respiratory function assessed when
      exposed to methacholine at doses of 0 (saline only), 0.42, 1.6 and 3.8 mg/kg. WBP
      assessment was performed in rats in a crossover study design when treated with
      theophylline at doses of 0 (saline only), 3, 10 and 30 mg/kg. RESULTS: Data from
      the PP-HOP study confirmed the expected changes in ventilatory parameters and
      airway mechanics in response to inhaled methacholine, including an increase in
      pulmonary resistance and decrease in tidal volume. Data from the WBP crossover
      study demonstrated similar sensitivity and statistical power to detect changes in
      respiratory rate and tidal volume to a standard parallel group design.
      CONCLUSION: Measurement of PP-HOP in a stand-alone safety pharmacology study in
      conjunction with HOP assessment conducted as part of a toxicology study,
      represents an improved respiratory testing strategy for inhaled drugs. For
      compounds administered by other routes, we conclude that use of WBP using a
      crossover dosing design is a suitable alternative to parallel dosing groups, with
      a significant reduction in animal numbers and no loss of statistical power.

PMID- 29580877
TI  - Establishment of a novel microscale thermophoresis ligand-binding assay for
      characterization of SLC solute carriers using oligopeptide transporter PepT1
      (SLC15 family) as a model system.
AB  - INTRODUCTION: Membrane proteins represent roughly one third of the human proteome
      and many of them serve as targets of therapeutic drugs. An exception is the SLC
      solute carrier superfamily with only a handful of approved drugs targeting SLCs.
      Indeed, for many of the SLCs, the natural transport substrates are still unknown.
      A major limitation for SLCs has been the difficulty to thoroughly characterize
      these multimembrane spanning proteins. The intrinsic properties of membrane
      proteins with alternative hydrophobic and hydrophilic domains lead to
      instability, making the purification tasks even more challenging compared to
      soluble proteins. This issue also holds true for conventional ligand-binding
      assays (LBAs) which usually require high-quality, pure and concentrated protein
      samples. Herein, we report a novel binding assay strategy to overcome these
      issues, taking advantage of a unique combination of yeast expression and
      microscale thermophoresis (MST). Following yeast overexpression of SLC15A1/PepT1
      ortholog from moss Physcomitrella patens, PepTPp, which exhibits remarkable
      similarity to human PepT1, the approach was validated using dipeptide
      glycylsarcosine (Gly-Sar) and antiviral prodrug valacyclovir as test substrates.
      METHOD: The originality of our approach is based on the comparative analysis of
      solubilized total membrane preparations with or without expression of the SLC
      target of interest, using a yeast strain (S. cerevisiae), in which the
      corresponding endogenous SLC homolog is depleted. MST is a recently developed
      technique that takes advantage of the properties of biomolecules in solution to
      migrate along a temperature gradient. Importantly, this migration is affected by
      substrate binding. It is being monitored by fluorescence using labelled SLC
      molecules in the presence of different ligand concentrations. RESULTS: We herein
      report a novel MST/yeast-based method to characterize binding of ligands to SLCs
      without the need for a prior SLC-purification step. For validation purposes, we
      used a close eukaryotic homolog of the human H+-coupled oligopeptide transporter
      PepT1 (SLC15A1) that mediates uptake of di-tripeptides and peptide-like drugs as
      a test model. This approach allowed the successful confirmation of the binding of
      Gly-Sar at the mM range and revealed for the first time the KD of the antiviral
      prodrug valacyclovir to the PepT1 homolog at around 50 MUM. DISCUSSION: This
      novel LBA approach is independent of protein purification. It is suitable for
      drug discovery as it is upscalable to high throughput compound screening. It
      works well for SLC transporters which are underrepresented targets due to their
      difficulties to study them. Moreover, this approach could make a significant
      contribution toward "deorphanization" of SLCs, revealing their transport
      substrates.

PMID- 29580878
TI  - Multidisciplinary Conference and Clinical Management of Rectal Cancer.
AB  - BACKGROUND: Presentation of rectal cancer cases at a colorectal cancer
      multidisciplinary conference (CRC-MDC) is a required standard for the newly
      formed National Accreditation Program for Rectal Cancer administered by the
      Commission on Cancer. The aim of this study was to determine the frequency and
      manner in which CRC-MDC changed the management of rectal cancer patients at a
      tertiary academic center. STUDY DESIGN: All rectal cancer cases presented at a
      weekly CRC-MDC between July 2015 and June 2016 were prospectively included.
      Patient demographics and clinical information were recorded. The presenting
      physician completed a uniform written questionnaire outlining any changes in
      management as a result of the discussion. RESULTS: There were 408 rectal cancer
      cases included, and survey responses were obtained for 371 (91%). Thirty-nine
      patients (11%) had stage IV disease and 20 (5%) had locally recurrent cancer.
      There was a documented change in plan as a result of the CRC-MDC discussion in 97
      of 371 (26%) cases surveyed. Changes in management included a change in therapy
      or change in therapy sequence in 76 cases, and recommendation of additional
      evaluation in 36 cases. Rates of management change were similar regardless of
      surgeon experience. Changes occurred in 23%, 28%, and 26% of cases presented by
      surgeons with <10, 10 to 20, and >20 years of experience, respectively (chi
      square p = 0.63). CONCLUSIONS: The CRC-MDC changes clinical management for a
      significant portion of rectal cancer patients at a tertiary center, independent
      of the presenting surgeon's years of clinical experience. Our results support the
      CRC-MDC standard for the National Accreditation Program for Rectal Cancer.

PMID- 29580879
TI  - Evaluating the Relevance of the 2013 Tokyo Guidelines for the Diagnosis and
      Management of Cholecystitis.
AB  - BACKGROUND: The 2013 Tokyo Guidelines (TG13) are used to diagnose, grade
      severity, and guide management of acute cholecystitis (AC). The aim of our study
      was to verify the diagnostic criteria, severity assessment, and management
      protocols based on the TG13. STUDY DESIGN: Our prospectively maintained emergency
      general surgery registry was used to review patients who had a surgical
      consultation for right upper quadrant pain (from 2013 to 2015). Diagnosis and
      severity were graded based on TG13 and compared with pathology reports. Our
      institutional management protocols were compared with TG13. RESULTS: Nine hundred
      and fifty-two patients were analyzed, of which 857 had biliary diseases. Mean age
      was 42 +/- 18 years and 67% were female. Seven hundred and seventy-nine had a
      cholecystectomy, 15 underwent cholecystostomy tube placement, and 63 patients
      were managed conservatively. Only 4% were febrile on presentation and 51% of
      patients had leukocytosis. Fifty-nine percent of patients did not have any signs
      of AC on ultrasonography. The TG13 criteria had a sensitivity of 53% for
      diagnosing AC (definitive 27%, suspected 26%, and undiagnosed 47%) when compared
      with the final pathology report; 92.5% of patients with grade I, 93% with grade
      II, and even 64% with grade III, underwent cholecystectomy safely at our
      institute. There were no differences in complication rates (3.7% vs 4.7%; p =
      0.81), return to operating room rates (0.6% vs 0.7%; p = 0.95), or mortality
      rates (0.3% vs 0%; p = 0.96) between grade I and grade II patients who underwent
      early cholecystectomy. CONCLUSIONS: The TG13 diagnostic criteria lack sensitivity
      and missed more than half of the patients with AC, as many patients lack clinical
      signs (fever and leukocytosis). The TG13 recommendations for conservative
      management and delayed cholecystectomy in grade II and grade III disease are not
      warranted.

PMID- 29580880
TI  - What Are the Most Significant Cost and Value Drivers for Pancreatic Resection in
      an Integrated Healthcare System?
AB  - BACKGROUND: An initiative was established to improve value-based care for
      pancreatic surgery in a large nonprofit health system. Cost data were presented
      bimonthly to a hepatobiliary clinical performance group via videoconference.
      STUDY DESIGN: The direct costs were calculated for all patients undergoing distal
      pancreatectomy (DP) and pancreaticoduodenectomy (PD) between January 2014 and
      July 2017. Median length of stay, 30-day and 90-day mortality rates, readmission
      rate, and costs were stratified by surgeon volume using 2 published criteria:
      "volume pledge" criteria (>=5 PDs/year) and Leapfrog criteria (>=11 PDs/year).
      RESULTS: There were 270 DPs and 526 PDs performed in 14 hospitals spanning 4
      states. Median PD costs were lower for high-volume surgeons (>=5 PDs/year),
      $21,026 vs $24,706 (p = 0.005). High-volume surgeons had a shorter length of stay
      (9 days vs 11 days; p < 0.001) for PD and DP (6 days vs 7 days; p = 0.001).
      Increased costs for low-volume surgeons included operative/anesthesia costs
      ($7,321 vs $6,325; p = 0.03), room and board ($5,828 vs $4,580; p = 0.01), and
      intensive care costs ($4,464 vs $3,113; p = 0.04). Operating time was increased
      for high-volume surgeons for DP and PD (p < 0.001). There was no difference in 30
      day or 90-day mortality rates or readmissions for DP or PD when stratified by
      volume pledge criteria. There was no difference in total costs for DP or PD when
      stratified by Leapfrog criteria. CONCLUSIONS: There was a significant cost
      reduction for PD but not DP when the threshold of 5 PDs was used as a definition
      of high volume. The sharing of detailed financial data with HPB surgeons on a
      regular basis provides an opportunity to evaluate practice patterns and thereby
      reduce direct costs.

PMID- 29580881
TI  - Doping risk and career turning points in male elite road cycling (2005-2016).
AB  - OBJECTIVES: Determine whether career paths of elite male professional riders
      explain the risk of being sanctioned for an Anti-Doping Rules Violation through
      the International Cycling Union. DESIGN, METHODS: A discrete-time logit model
      explored the link between career path and ADRV risk in a database of 10,551
      riders engaged in the first three world divisions (2005-2016), including 271
      sanctioned riders. RESULTS: Despite a longer career (7.8years), sanctioned riders
      have a precarious path. The odds of finding a sanctioned rider within those who
      experienced a career interruption is 5.80 times higher than for a non-caught one.
      61% of the caught riders have experienced a team change. The odds of finding a
      caught rider within those who experienced such a change is 1.35 times higher. 44%
      of caught riders start before 23years, vs 34% for non-sanctioned ones. The odds
      of being sanctioned are 1.69 times higher for doped riders beginning before 23.
      The odds of finding a sanctioned rider are 1.94 times higher among those starting
      their careers before 2005 (establishment of Pro Tour), than those who started in
      2008 or after. In that year, the Cycling Anti-Doping Foundation and the biologic
      passport were both launched. CONCLUSIONS: Caught riders could have extended their
      more precarious careers with doping. The post-2005 generation effect could mean
      that riders are cleaner or slicker at hiding doping. The higher risk of being
      caught for riders starting after 23 might indicate that an early professional
      socialization reduces the risk by teaching them to be cleaner, or better at
      hiding doping.

PMID- 29580882
TI  - Astrocytes and neurons in locus coeruleus mediate restraint water immersion
      stress-induced gastric mucosal damage through the ERK1/2 signaling pathway.
AB  - Restraint water-immersion stress (RWIS) is considered to be a compound stress
      model that includes psychological and physical stimulation and may cause gastric
      mucosal damage. Studies have shown that locus coeruleus (LC) is involved in the
      gastrointestinal function, but whether it is involved in RWIS-induced gastric
      mucosal damage has not yet been reported. Here, we investigated the expression of
      glial fibrillary acidic protein (GFAP), c-Fos, and phosphorylation extracellular
      signal regulated kinase 1/2 (p-ERK1/2) in the LC after RWIS using
      immunocytochemical staining and western blotting in order to explore whether the
      ERK1/2 signaling pathway interacts with the neuron-astrocyte network in the LC
      during RWIS and whether it is involved in causing RWIS-induced gastric mucosal
      damage. Expression of c-Fos, GFAP, and p-ERK1/2 increased significantly following
      RWIS and peaked at 3 h after RWIS. After intracerebroventricular injection of c
      Fos antisense oligodeoxynucleotides (ASO) and astrocytic toxin L-a-aminoadipate
      (L-AA), the gastric mucosal damage and the activation of neurons and astrocytes
      in the LC significantly decreased. Intracerebroventricular injection of ERK1/2
      signaling pathway inhibitor PD98059 suppressed gastric mucosal damage as well as
      the RWIS-induced activation of neurons and astrocytes in the LC. Activation of LC
      neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may
      play a critical role in RWIS-induced gastric mucosa damage.

PMID- 29580883
TI  - Cre-expressing neurons in the cortical white matter of Ntsr1-Cre GN220 mice.
AB  - Genetically modified mouse strains that express Cre-recombinase in specific
      neuronal sub-populations have become widely used tools for investigating neuronal
      function. The Ntsr1-Cre GN220 mouse expresses this enzyme in corticothalamic
      neurons in layer 6 of cerebral cortex. We observed that about 7% of Cre
      expressing cells in the primary visual cortex are found within the white matter
      bordering layer 6. By using the immunohistochemical marker for layer 6 neurons,
      Forkhead box protein 2 (FoxP2), and fluorescently conjugated latex beads injected
      into the dorsal lateral geniculate nucleus, we show that about half of these
      cells are similar to and could belong to the layer 6 corticothalamic neuron
      population. The other half seems to be a distinct white matter (WM) neuron sub
      population that we estimate to constitute 2-4% of the total cortical Cre
      expressing population. Staining for the neuronal marker Neuronal nuclei (NeuN)
      revealed that about 15-40% of WM neurons are Cre-expressing. Thus, the potential
      contribution from WM neurons needs to be considered when interpreting the results
      from experiments using the Ntsr1-Cre GN220 mouse for investigating
      corticothalamic neuronal function.

PMID- 29580884
TI  - Mycobacterium tuberculosis.
AB  - In this infographic, the genetics, phylogeny, physiology, and pathogenesis
      mechanisms of Mycobacterium tuberculosis are shown. Mycobacterium tuberculosis is
      the etiological agent of tuberculosis (TB), the leading cause of death due to a
      single infectious agent, claiming 1.7 million lives in 2016. Of the deaths
      attributable to TB in 2016, 22% occurred in people coinfected with HIV, and close
      to 5% of the 10.4 million incident cases of this disease were resistant to at
      least two of the first-line TB drugs. In this infographic, we describe the
      fundamental features of the genetics, phylogeny, and physiology of this member of
      the phylum Actinobacteria, which is associated increasingly with drug resistance
      mediated by mutations and rearrangements in its single, circular chromosome. We
      also highlight the key pathogenesis mechanisms employed by this slow-growing,
      facultative intracellular bacterium, which include avoidance of host cell
      clearance by arrest of the normal macrophage maturation process.

PMID- 29580886
TI  - Physical Activity and Sarcopenia in the Geriatric Population: A Systematic
      Review.
AB  - INTRODUCTION: Sarcopenia is an aging-related health problem in the geriatric
      population. Sarcopenia reduces muscle mass, muscle strength, and physical
      performance. Although physical activity is protective against sarcopenia for
      older adults, there are limited studies in this area. The purpose of this study
      was to integrate and analyze research on physical activity and sarcopenia in the
      geriatric population. METHODS: Studies that assess sarcopenia were searched
      across electronic databases that included Medline, PubMed, CINAHL, and Cochrane
      Database of Systematic Reviews. Studies that implemented physical activity
      related intervention or research were included. A critical appraisal skills
      program was used for quality assessment of the selected articles. Study selection
      and data extraction were counted by 2 independent reviewers. RESULTS: Of the 149
      references identified through the database search, 10 studies were included in
      this systematic review. Seven studies were randomized controlled trials, and 3
      were cross-sectional or longitudinal. The results of 8 studies indicated
      significant improvement in muscle mass, muscle strength, and physical performance
      through exercise intervention, as determined by long-term observation.
      CONCLUSIONS: Physical activity is an effective protective strategy for
      sarcopenia. Most studies of older adults exercise intervention indicated that the
      participants achieved positive results, but maintenance of muscle strength
      appeared to depend on continuous implementation of certain types of physical
      activities. A limitation of these 10 reviewed studies was that there was no
      consistency in the measurement of sarcopenia. Therefore, sarcopenia measurement
      needs further investigation.

PMID- 29580885
TI  - Prophylaxis of Venous Thromboembolism in Geriatric Settings: A Cluster-Randomized
      Multicomponent Interventional Trial.
AB  - OBJECTIVES: To evaluate the efficacy of an intervention on the practice of venous
      thromboembolism prevention. DESIGN: A multicenter, prospective, controlled,
      cluster-randomized, multifaceted intervention trial consisting of educational
      lectures, posters, and pocket cards reminding physicians of the guidelines for
      thromboprophylaxis use. SETTINGS: Twelve geriatric departments with 1861 beds
      total, of which 202, 803, and 856 in acute care, post-acute care, and long-term
      care wards, respectively. PARTICIPANTS: Patients hospitalized between January 1
      and May 31, 2015, in participating departments. MEASUREMENTS: The primary
      endpoint was the overall adequacy of thromboprophylaxis prescription at the
      patient level, defined as a composite endpoint consisting of indication, regimen,
      and duration of treatment. Geriatric departments were divided into an
      intervention group (6 departments) and control group (6 departments). The
      preintervention period was 1 month to provide baseline practice levels, the
      intervention period 2 months, and the postintervention period 1 month in acute
      care and post-acute care wards or 2 months in long-term care wards. Multivariable
      regression was used to analyze factors associated with the composite outcome.
      RESULTS: We included 2962 patients (1426 preintervention and 1536
      postintervention), with median age 85 [79;90] years. For the overall 18.9% rate
      of inadequate thromboprophylaxis, 11.1% was attributable to underuse and 7.9%
      overuse. Intervention effects were more apparent in post-acute and long-term care
      wards although not significantly [odds ratio 1.44 (95% confidence interval
      0.78;2.66), P = .241; and 1.44 (0.68, 3.06), P = .345]. Adequacy rates
      significantly improved in the postintervention period for the intervention group
      overall (from 78.9% to 83.4%; P = .027) and in post-acute care (from 75.4% to
      86.3%; P = .004) and long-term care (from 87.0% to 91.7%; P = .050) wards, with
      no significant trend observed in the control group. CONCLUSIONS/IMPLICATIONS:
      This study failed to demonstrate improvement in prophylaxis adequacy with our
      intervention. However, the intervention seemed to improve practices in post-acute
      and long-term care but not acute care wards.

PMID- 29580887
TI  - Neuroimaging correlates of narcolepsy with cataplexy: A systematic review.
AB  - Recent developments in neuroimaging techniques have advanced our understanding of
      biological mechanisms underpinning narcolepsy. We used MEDLINE to retrieve
      neuroimaging studies to compare patients with narcolepsy and healthy controls.
      Thirty-seven studies were identified and demonstrated several replicated
      abnormalities: (1) gray matter reductions in superior frontal, superior and
      inferior temporal, and middle occipital gyri, hypothalamus, amygdala, insula,
      hippocampus, cingulate cortex, thalamus, and nucleus accumbens, (2) decreased
      fractional anisotropy in white matter of fronto-orbital and cingulate area, (3)
      reduced brain metabolism or cerebral blood flow in middle and superior frontal,
      and cingulate cortex (4) increased activity in inferior frontal gyri, insula,
      amygdala, and nucleus accumbens, and (5) N-acetylaspartate/creatine
      phosphocreatine level reduction in hypothalamus. In conclusion, all the
      replicated findings are still controversial due to the limitations such as
      heterogeneity or size of the samples and lack of multimodal imaging or follow-up.
      Thus, future neuroimaging studies should employ multimodal imaging methods in a
      large sample size of patients with narcolepsy and consider age, duration of
      disease, age at onset, severity, human leukocyte antigen type, cerebrospinal
      fluid hypocretin levels, and medication intake in order to elucidate possible
      neuroimaging characteristic of narcolepsy and identify therapeutic targets.

PMID- 29580888
TI  - Characterization of mouse chorda tympani responses evoked by stimulation of
      anterior or posterior fungiform taste papillae.
AB  - Different gustatory papilla types vary in their locations on the tongue.
      Distinctions have often made between types, but variation within fungiform
      papillae has seldom been explored. Here, regional differences in fungiform
      papillae were investigated by flowing solutions selectively over either an
      anterior fungiform (AF, tongue tip) or a posterior fungiform (PF, middle third)
      region as taste-evoked activity was measured in the chorda tympani nerve of
      C57BL/6J (B6) mice. Significantly larger responses were evoked by NaCl applied to
      the AF than PF region, and the ENaC blocker amiloride reduced the NaCl response
      size only for the former. Umami synergy, based on co-presenting MSG and IMP, was
      larger for the AF than PF region. The regions did not differ in response size to
      sour chemicals, but responses to l-lysine, l-arginine, sucrose, and tetrasodium
      pyrophosphate were larger for the AF than PF region. Thus, fungiform papillae on
      the tongue tip differed from those found further back in their transduction
      mechanisms for salty and umami compounds. Gustatory sensitivity also showed
      regional variation, albeit with a complex relationship to palatability and taste
      quality. Overall, the data support a regional organization for the mouse tongue,
      with different functional zones for the anterior, middle, and posterior thirds.

PMID- 29580889
TI  - Behavioral evaluation of auditory stream segregation in rats.
AB  - Perceptual organization of sound sequences into separate sound sources or streams
      is called auditory stream segregation. Neural substrates for this process in both
      the spectral and temporal domains remain to be elucidated. Despite abundant
      knowledge about their auditory physiology, behavioral evidence for auditory
      streaming in rodents is still limited. We provided behavioral evidence for
      auditory streaming in the go/no-go discrimination task, but not in the two
      alternative choice task. In the go/no-go discrimination phase, rats were able to
      discriminate different rhythms corresponding to segregated or integrated tone
      sequences in both short inter-tone interval (ITI) and long ITI conditions.
      Nevertheless, performance was poorer in the long ITI group. In probe testing,
      which assessed the ability to discriminate one of the segregated tone sequences
      from ABA- tone sequences, the detection rate increased with the difference in
      frequency (DeltaF) for short (100 ms), but not long (200 ms) ITIs. Our results
      indicate that auditory streaming in rats on both the spectral and temporal
      features in the ABA- tone paradigm is qualitatively analogous to that observed in
      human psychophysics studies. This suggests that rodents are a valuable model for
      investigating the neural substrates of auditory streaming.

PMID- 29580890
TI  - Mifepristone attenuates depression-like changes induced by chronic central
      administration of interleukin-1beta in rats.
AB  - Increased proinflammatory cytokines, such as interleukin (IL)-1beta, may play an
      important role in the etiology of depression because they cause the hypothalamic
      pituitary-adrenal axis to release glucocorticoids (GC) and induce dysfunction of
      serotonin and norepinephrine neurotransmission. Sustained increase in GC may
      activate microglia to induce neuroinflammation, and suppress astrocytes to
      produce neurotrophins, which lead to neuronal apoptosis. Here, we tested the
      hypothesis that glucocorticoid receptor (GR) antagonist mifepristone (RU486) may
      attenuate IL-1beta-induced depression-like behavior by regulating the
      neuroinflammation and neurotrophin functions of microglia and astrocytes. Rats
      received intracerebroventricular injections of IL-1beta (10 ng) and/or
      subcutaneous injections of RU486 for 14 days. Then animal depression-like
      behaviors, serum corticosterone concentration, the levels of pro-inflammatory
      cytokines (TNF-alpha, IL-6), mRNA and protein expressions of CD11b, GFAP and
      neurotrophins (pro-BDNF, BDNF, GDNF and their receptors TrkB, p75, GFRalpha-1 and
      GFRalpha-2) in the amygdala were studied. Compared to controls, significantly
      decreased rearing score and increased defecation in the open field test,
      decreases in ratio of open/closed time in the elevated plus maze and in sucrose
      preference, while increased level of corticosterone in the serum were found in
      the rats administrated with IL-1beta. IL-1beta administration also reduced the
      expressions of GFAP, BDNF, GDNF and its receptor GFR-alpha1, but increased the
      expressions of CD11b, pro-BDNF, p75 and pro-inflammatory cytokines (TNF-alpha, IL
      6) concentrations. RU486 treatment markedly attenuated these changes induced by
      IL-1beta, except for the expressions of GFR-alpha1. In conclusion, RU486 may
      improve depression-like changes by suppressing microglia and inflammation and
      promoting astrocytes to restore neurotrophin function.

PMID- 29580891
TI  - Repeated social stress leads to contrasting patterns of structural plasticity in
      the amygdala and hippocampus.
AB  - Previous studies have demonstrated that repeated immobilization and restraint
      stress cause contrasting patterns of dendritic reorganization as well as
      alterations in spine density in amygdalar and hippocampal neurons. Whether social
      and ethologically relevant stressors can induce similar patterns of morphological
      plasticity remains largely unexplored. Hence, we assessed the effects of repeated
      social defeat stress on neuronal morphology in basolateral amygdala (BLA),
      hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats
      experienced social defeat stress on 5 consecutive days during confrontation in
      the resident-intruder paradigm with larger and aggressive Wild-type Groningen
      rats. This resulted in clear social avoidance behavior one day after the last
      confrontation. To assess the morphological consequences of repeated social
      defeat, 2 weeks after the last defeat, animals were sacrificed and brains were
      stained using a Golgi-Cox procedure. Morphometric analyses revealed that,
      compared to controls, defeated Wistar rats showed apical dendritic decrease in
      spine density on CA1 but not BLA. Sholl analysis demonstrated a significant
      dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal
      dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in
      defeated animals. Social stress failed to induce lasting structural changes in
      mPFC neurons. Our findings demonstrate for the first time that social defeat
      stress elicits divergent patterns of structural plasticity in the hippocampus
      versus amygdala, similar to what has previously been reported with repeated
      physical stressors. Therefore, brain region specific variations may be a
      universal feature of stress-induced plasticity that is shared by both physical
      and social stressors.

PMID- 29580893
TI  - D-Cycloserine Facilitates Reversal in an Animal Model of Post-traumatic Stress
      Disorder.
AB  - Many psychiatric disorders are associated with cognitive dysfunction that is
      ineffectively treated by existing pharmacotherapies and which may contribute to
      poor real-world functioning. D-cycloserine (DCS) is a partial N-methyl-D
      aspartate (NMDA) agonist that has attracted attention because of its cognitive
      enhancing properties, including in people with post-traumatic stress disorder
      (PTSD). Here, we examined the effect of DCS on reversal learning - a type of
      cognitive flexibility - following exposure to single prolonged stress (SPS), a
      rodent model of PTSD. Male Sprague Dawley rats (n = 64) were trained to press
      levers in an operant chamber, matched for performance and assigned to SPS or
      control (unstressed) groups. Following SPS, rats received three additional lever
      press sessions, followed by a side bias test on day three. One day later they
      learned a response discrimination rule (press left or right lever, opposite to
      side bias) and on a subsequent day were trained (and tested) for reversal to the
      opposite lever. DCS (15 mg/kg) or vehicle was administered 30 minutes prior to
      the reversal session. No between-group differences were found in acquisition or
      retrieval of the initial rule, but a significant drug x stress interaction on
      response discrimination reversal indicated that DCS had a greater beneficial
      effect on SPS rats' cognitive flexibility than it did on performance in controls.
      These findings add to a growing literature on the beneficial effects of DCS for
      treating a wide variety of deficits that develop following exposure to extreme
      stress and may have implications for the development of novel pharmacotherapies
      for PTSD.

PMID- 29580892
TI  - Cocaine- and amphetamine-regulated transcript peptide (CART) induced reward
      behavior is mediated via Gi/o dependent phosphorylation of PKA/ERK/CREB pathway.
AB  - Although the role of cocaine- and amphetamine-regulated transcript peptide (CART)
      in modulating the mesolimbic reward pathway has been suggested, underlying
      cellular mechanisms have not been elucidated. Herein, we investigate the
      involvement of Gi/o dependent protein kinase A (PKA)/extracellular signal
      regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling in
      CART induced reward behavior. The rat was implanted with a stimulating electrode
      targeted at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) and
      conditioned to intracranial self-stimulation (ICSS) in an operant chamber.
      Intracerebroventricular (icv) administration of CART (55-102) dose-dependently
      lowered ICSS threshold suggesting reward promoting action, however, pretreatment
      with subeffective doses of Gi/o inhibitor (pertussis toxin, PTX) or PKA inhibitor
      (Rp-cAMPS) or ERK inhibitor (U0126) via icv route, attenuated CART mediated
      reward experience. Operant conditioned rats showed increased pCREB levels in the
      nucleus accumbens shell (AcbSh), ventral tegmental area (VTA) and hypothalamic
      paraventricular nucleus (PVN). Infusion of CART (icv) in the conditioned rats
      augmented the population of pCREB positive cells in the AcbSh, VTA and PVN areas,
      but not in the arcuate nucleus (ARC). Pretreatment with U0126 significantly
      decreased CART induced pCREB activation in the AcbSh and VTA, but not in PVN and
      ARC. ICSS or CART induced CREB mRNA expression in Acb and VTA was attenuated by
      U0126. We suggest that recruitment of Gi/o dependent PKA/ERK/CREB phosphorylation
      signaling in Acb and VTA might play an important role in CART induced reward
      behavior.

PMID- 29580894
TI  - Gut microbiota profiles in treatment-naive children with attention deficit
      hyperactivity disorder.
AB  - BACKGROUNDS: Although increasing evidence suggests a role for the gut microbiota
      in neurodevelopment, the actual structure and composition of microbiota in
      children with attention-deficit/hyperactivity disorder (ADHD) remain unclear.
      METHODS: Thus, the present study aimed to define the characteristics of gut
      microbiota in treatment-naive children with ADHD and to assess their relationship
      with the severity of ADHD symptoms. High-throughput pyrosequencing was used to
      investigate the microbiota composition in fecal matter from 51 children with ADHD
      and 32 healthy controls (HC). RESULTS: An operational taxonomical unit (OTU)
      level analysis revealed a significant decrease in the fractional representation
      of Faecalibacterium in children with ADHD compared to HC. In individuals with
      ADHD, the abundance of Faecalibacterium was negatively associated with parental
      reports of ADHD symptoms. However, there was no significant difference in alpha
      diversity between the ADHD and control groups. CONCLUSIONS: This present findings
      support the involvement of microbiota alteration in psychiatric diseases and
      Faecalibacterium may represent a potential novel marker of gut microbiota in
      ADHD. Future studies are needed to validate these findings and to elucidate the
      temporal and causal relationships between these variables.

PMID- 29580895
TI  - Effect of mobile laminar airflow units on airborne bacterial contamination during
      neurosurgical procedures.
AB  - BACKGROUND: Surgical site infections (SSIs) after neurosurgery are potentially
      life-threatening and entail great costs. SSIs may occur from airborne bacteria in
      the operating room, and ultraclean air is desired during infection-prone cleaning
      procedures. Door openings and the number of persons present in the operating room
      affect the air quality. Mobile laminar airflow (MLAF) units, with horizontal
      laminar airflow, have previously been shown to reduce airborne bacterial
      contamination. AIM: To assess the effect of MLAF units on airborne bacterial
      contamination during neurosurgical procedures. METHODS: In a quasi-experimental
      design, bacteria-carrying particles (colony-forming units: cfu) during
      neurosurgical procedures were measured with active air-sampling in operating
      rooms with conventional turbulent ventilation, and with additional MLAF units.
      The MLAF units were shifted between operating rooms monthly. Colony-forming unit
      count and bacterial species detection were conducted after incubation. Data was
      collected for a period of 18 months. FINDINGS: A total of 233 samples were
      collected during 45 neurosurgical procedures. The use of MLAF units significantly
      reduced the numbers of cfu in the surgical site area (P < 0.001) and above the
      instrument table (P < 0.001). Logistic regression showed that the only
      significant predictor affecting cfu count was the use of MLAF units (odds ratio:
      41.6; 95% confidence interval: 11.3-152.8; P < 0.001). The most frequently
      detected bacteria were coagulase-negative staphylococci. CONCLUSION: MLAF
      successfully reduces cfu during neurosurgery to ultraclean air levels. MLAF units
      are valuable when the main operating room ventilation system is unable to produce
      ultraclean air in infection-prone clean neurosurgery.

PMID- 29580896
TI  - p53 and glucose metabolism: an orchestra to be directed in cancer therapy.
AB  - Metabolic reprogramming is a hallmark of cancer with a strong impact on tumor
      cell survival, proliferation, dissemination, and resistance to therapy. As such,
      it has represented a promising therapeutic target for cancer. Although cancer
      cells may exhibit a wide range of metabolic profiles, the enhancement of aerobic
      glycolysis to generate lactate and ATP (Warburg effect) is a cancer-associated
      trait, which is under regulation of both oncogenes and tumor suppressor genes.
      Particularly, the tumor suppressor protein p53 was shown to revert the Warburg
      effect, and to negatively influence the oncogenic metabolic adaption of cancer
      cells. This review provides a systematization of the p53 influence on glycolysis
      and oxidative phosphorylation (OXPHOS), giving attention to the interplay of p53
      with key signaling pathways, including c-Myc, HIF-1, LKB1/AMPK, and PI3K/Akt, as
      well as to mutant p53 gain-of-function. It also contributes to a better
      understanding of distinct metabolic profiles in heterogeneous tumor cell
      populations, and of its impact on cancer therapeutic resistance. Additionally, a
      reflection on current strategies adopted in clinical trials to overcome
      therapeutic resistance is presented, highlighting the main limitations and future
      therapeutic perspectives based on metabolic reprogramming. In particular, this
      review emphasizes the p53 activation as a promising therapeutic strategy to
      reprogram tumor glucose metabolism, conducting to cell death. Moreover, potential
      synergisms between p53-activating agents and metabolic inhibitors are discussed,
      fostering the improvement of cancer therapy.

PMID- 29580898
TI  - Deep sequencing-based characterization of transcriptome of Pyrus ussuriensis in
      response to cold stress.
AB  - Pyrus ussuriensis is extremely cold hardy when fully acclimated, but knowledge
      relevant to the molecular mechanisms underlying this economically valuable trait
      is still limited so far. In this study, global transcriptome profiles of Pyrus
      ussuriensis under cold conditions (4  degrees C) over a time course were
      generated by high-throughput sequencing. In total, >57,121,199 high quality clean
      reads were obtained with approximately 11.0 M raw data for each library. Among
      them, the values of 66.84%-72.03% of clean reads in the digital transcript
      abundance measurement could be well mapped to the pear genome database, resulting
      in the identification of 8544 differentially expressed genes (DEGs) having 43
      Gene Ontology (GO) terms and 17 clusters of orthologous groups (COG) involved in
      385 Kyoto Encyclopedia of Genes and Genomes (KEGG) defined pathways. These
      comprised 3124 (1033 up-regulated, 2091 down-regulated), 1243 (729 up-regulated,
      514 down-regulated), and 750 (458 up-regulated, 292 down-regulated) genes from
      the cold-treated samples at 5, 12 and 24 h, respectively. The accuracy of the RNA
      Seq derived transcript expression data was validated by analyzing the expression
      patterns of 16 DGEs by quantitative real-time PCR. Plant-pathogen interaction,
      plant hormone signal transduction, Photosynthesis, signal transduction, innate
      immune response and response to biotic stimulus were the most significantly
      enriched GO categories among in the DEGs. A total of 335 transcription factors
      were shown to be cold responsive. In addition, a number of genes involved in the
      catabolism and signaling of hormones were significantly affected by the cold
      stress. The RNA-Seq and digital expression profiling provides valuable insights
      into the understanding the molecular events related to cold responses in Pyrus
      ussuriensis and dataset may help guide future identification and functional
      analysis of potential genes that are important for enhancing cold hardiness.

PMID- 29580897
TI  - Prevalence and risk factors of Giardia duodenalis in domestic rabbbits
      (Oryctolagus cuniculus) in Jilin and Liaoning province, northeastern China.
AB  - BACKGROUND: Giardia duodenalis is one of the most important intestinal parasites
      that can infect virtually all animals, including rabbits and humans. However,
      there is little information regarding the prevalence and genotypes of G.
      duodenalis in domestic rabbits in China. METHODS: A total of 426 rabbit fecal
      samples (136 from Shenyang City, 174 from Changchun City, and 116 from Jilin
      City) were examined by Lugol's iodine staining with microscopy analysis, and the
      positive samples were genotyped at the triosephosphate isomerase (tpi) and the
      beta giardin (bg) gene loci using nested PCR. RESULTS: Forty-two (9.86%) out of
      426 rabbit fecal samples were G. duodenalis-positive under microscopy analysis,
      and the highest G. duodenalis infection rate was 23.08% on farm 6. The prevalence
      of G. duodenalis in rabbits from different cities ranged from 1.47% to 14.37%.
      Among different age groups, G. duodenalis prevalence in rabbits ranged from 5.41%
      to 12.58%. The prevalence of G. duodenalis in outdoor rabbits and indoor rabbits
      was 14.29% and 6.77%, respectively. In the present study, region and farming mode
      were highly correlated with G. duodenalis infection in rabbits. All 42 G.
      duodenalis isolates were successfully amplified and sequenced at the tpi and bg
      loci, and only G. duodenalis assemblage B were identified. CONCLUSION: This study
      not only further confirmed the dominance of G. duodenalis assemblage B in
      rabbits, but also further improved the foundation data concerning the
      distribution of G. duodenalis assemblages in China.

PMID- 29580899
TI  - Investigation of candidate long noncoding RNAs and messenger RNAs in the
      immediate phase of spinal cord injury based on gene expression profiles.
AB  - Spinal cord injury (SCI) is a serious devastating condition and it has a high
      mortality rate and morbidity rate. The early pathological changes in the
      immediate phase of SCI may play a major part in the development of secondary
      injury. Alterations in the expression of many long noncoding RNAs (lncRNAs) have
      been shown to play fundamental roles in the diseases of the central nervous
      system. However, the roles of lncRNAs and messenger RNAs (mRNAs) in the immediate
      phase of SCI are not clear. We examined the expression of mRNAs and lncRNAs in a
      rat model at 2 h after SCI and identified the differentially expressed lncRNAs
      (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray
      analysis. 772 DE lncRNAs and 992 DE mRNAs were identified in spinal cord samples
      in the immediate phase following SCI compared with control samples. Moreover,
      Gene Ontology (GO) term annotation results showed that CXCR chemokine receptor
      binding, neutrophil apoptotic process, neutrophil migration, neutrophil
      extravasation, macrophage differentiation, monocyte chemotaxis and cellular
      response to interleukin-1 (IL-1) were the main significantly enriched GO terms.
      The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis
      showed that the DEGs were enriched in toll-like receptor signaling pathway, p53
      signaling pathway, MAPK signaling pathway and Jak-STAT signaling pathway. IL6,
      MBOAT4, FOS, TNF, JUN, STAT3, CSF2, MYC, CCL2 and FGF2 were the top 10 high
      degree hub nodes and may be important targets in the immediate phase of SCI. The
      current study on provides novel insights into how lncRNAs and mRNAs regulate the
      pathogenesis of the immediate phase after SCI.

PMID- 29580900
TI  - Deletion of the endogenous TrkB.T1 receptor isoform restores the number of
      hippocampal CA1 parvalbumin-positive neurons and rescues long-term potentiation
      in pre-symptomatic mSOD1(G93A) ALS mice.
AB  - Amyotrophic lateral sclerosis (ALS) causes rapidly progressive paralysis and
      death within 5 years from diagnosis due to degeneration of the motor circuits.
      However, a significant population of ALS patients also shows cognitive
      impairments and progressive hippocampal pathology. Likewise, the mutant
      SOD1(G93A) mouse model of ALS (mSOD1), in addition to loss of spinal motor
      neurons, displays altered spatial behavior and hippocampal abnormalities
      including loss of parvalbumin-positive interneurons (PVi) and enhanced long-term
      potentiation (LTP). However, the cellular and molecular mechanisms underlying
      these morpho-functional features are not well understood. Since removal of
      TrkB.T1, a receptor isoform of the brain-derived neurotrophic factor, can
      partially rescue the phenotype of the mSOD1 mice, here we tested whether removal
      of TrkB.T1 can normalize the number of PVi and the LTP in this model.
      Stereological analysis of hippocampal PVi in control, TrkB.T1-/-, mSOD1, and
      mSOD1 mice deficient for TrkB.T1 (mSOD1/T1-/-) showed that deletion of TrkB.T1
      restored the number of PVi to physiological level in the mSOD1 hippocampus. The
      rescue of PVi neuron number is paralleled by a normalization of high-frequency
      stimulation-induced LTP in the pre-symptomatic mSOD1/T1-/- mice. Our experiments
      identified TrkB.T1 as a cellular player involved in the homeostasis of
      parvalbumin expressing interneurons and, in the context of murine ALS, show that
      TrkB.T1 is involved in the mechanism underlying structural and functional
      hippocampal degeneration. These findings have potential implications for
      hippocampal degeneration and cognitive impairments reported in ALS patients at
      early stages of the disease.

PMID- 29580902
TI  - Early life trauma: An exploratory study of effects on OXTR and NR3C1 gene
      expression and nurturing self-efficacy in mothers of infants.
AB  - BACKGROUND: In animals, adverse early experience alters oxytocinergic and
      glucocorticoid activity and maternal behavior in adulthood. This preliminary
      study explored associations among childhood trauma (loss of a parent or sexual
      abuse in childhood), maternal self-efficacy, and leukocyte gene expression (mRNA)
      of oxytocin and glucocorticoid receptors (OXTR and NR3C1) in mothers of infants.
      METHODS: 62 mothers (20 with early life trauma) with healthy 3-month old infants
      reported maternal self-efficacy, depression, infant temperament, and overall
      social support; the effects of early trauma on these measures were assessed. Of
      these, 35 mothers (14 with early trauma) underwent blood draws after 2 infant
      feeding times; their OXTR and NR3C1 mRNA was compared to a control group of 25 no
      infant women without early trauma, and also was examined for associations with
      self-efficacy. RESULTS: OXTR mRNA was increased in mothers of infants versus no
      infant controls (p < 0.0003), and mothers with greatest prior maternal experience
      had higher OXTR than those with less experience (0-2 vs. 3+ older children, p <
      0.033). Mothers with early trauma and less maternal experience had lower OXTR
      mRNA than no-trauma mothers (p < 0.029) and lower NR3C1 mRNA than controls (p <
      0.004). Mothers with depression also had lower NR3C1 than other mothers (p <
      0.003) but did not differ in OXTR. Mothers with early trauma also reported their
      support network to be less helpful and more upsetting and unpredictable than
      other mothers (p < 0.035-p < 0.005). Regarding maternal behavior, in mothers with
      early trauma, helpful support networks increased self-reported nurturing self
      efficacy when babies were not fussy but decreased it with fussy babies (p <
      0.05). Support was unrelated to self-efficacy in no-trauma mothers. Similarly,
      among mothers with low OXTR or NR3C1 (-1SD, most having early trauma and lower
      maternal experience), greater support was associated with lower self-efficacy (p
      < 0.05), while mothers with high OXTR or NR3C1 (+1SD) tended to have higher self
      efficacy with greater support. CONCLUSIONS: These preliminary findings need
      confirmation in a larger sample but suggest that childhood trauma influences
      maternal behavior and both OXTR and NR3C1 pathways in mothers of infants, and
      that both depression and prior maternal experience may be other important
      factors. Effects on maternal behavior appear to require more complex modeling.

PMID- 29580903
TI  - Neuromagnetic correlates of audiovisual word processing in the developing brain.
AB  - The brain undergoes enormous changes during childhood. Little is known about how
      the brain develops to serve word processing. The objective of the present study
      was to investigate the maturational changes of word processing in children and
      adolescents using magnetoencephalography (MEG). Responses to a word processing
      task were investigated in sixty healthy participants. Each participant was
      presented with simultaneous visual and auditory word pairs in "match" and
      "mismatch" conditions. The patterns of neuromagnetic activation from MEG
      recordings were analyzed at both sensor and source levels. Topography and source
      imaging revealed that word processing transitioned from bilateral connections to
      unilateral connections as age increased from 6 to 17 years old. Correlation
      analyses of language networks revealed that the path length of word processing
      networks negatively correlated with age (r = -0.833, p < 0.0001), while the
      connection strength (r = 0.541, p < 0.01) and the clustering coefficient (r =
      0.705, p < 0.001) of word processing networks were positively correlated with
      age. In addition, males had more visual connections, whereas females had more
      auditory connections. The correlations between gender and path length, gender and
      connection strength, and gender and clustering coefficient demonstrated a
      developmental trend without reaching statistical significance. The results
      indicate that the developmental trajectory of word processing is gender specific.
      Since the neuromagnetic signatures of these gender-specific paths to adult word
      processing were determined using non-invasive, objective, and quantitative
      methods, the results may play a key role in understanding language impairments in
      pediatric patients in the future.

PMID- 29580901
TI  - Species-conserved SYNGAP1 phenotypes associated with neurodevelopmental
      disorders.
AB  - SYNGAP1 loss-of-function variants are causally associated with intellectual
      disability, severe epilepsy, autism spectrum disorder and schizophrenia. While
      there are hundreds of genetic risk factors for neurodevelopmental disorders
      (NDDs), this gene is somewhat unique because of the frequency and penetrance of
      loss-of-function variants found in patients combined with the range of brain
      disorders associated with SYNGAP1 pathogenicity. These clinical findings indicate
      that SYNGAP1 regulates fundamental neurodevelopmental processes that are
      necessary for brain development. Here, we describe four phenotypic domains that
      are controlled by Syngap1 expression across vertebrate species. Two domains, the
      maturation of cognitive functions and maintenance of excitatory-inhibitory
      balance, are defined exclusively through a review of the current literature. Two
      additional domains are defined by integrating the current literature with new
      data indicating that SYNGAP1/Syngap1 regulates innate survival behaviors and
      brain structure. These four phenotypic domains are commonly disrupted in NDDs,
      suggesting that a deeper understanding of developmental Syngap1 functions will be
      generalizable to other NDDs of known or unknown etiology. Therefore, we discuss
      the known molecular and cellular functions of Syngap1 and consider how these
      functions may contribute to the emergence of disease-relevant phenotypes.
      Finally, we identify major unexplored areas of Syngap1 neurobiology and discuss
      how a deeper understanding of this gene may uncover general principles of NDD
      pathobiology.

PMID- 29580904
TI  - Different profiles of decision making and physiology under varying levels of
      stress in trained military personnel.
AB  - Decision making is one of the most vital processes we use every day, ranging from
      mundane decisions about what to eat to life-threatening choices such as how to
      avoid a car collision. Thus, the context in which our decisions are made is
      critical, and our physiology enables adaptive responses that account for how
      environmental stress influences our performance. The relationship between stress
      and decision making can additionally be affected by one's expertise in making
      decisions in high-threat environments, where experts can develop an adaptive
      response that mitigates the negative impacts of stress. In the present study, 26
      male military personnel made friend/foe discriminations in an environment where
      we manipulated the level of stress. In the high-stress condition, participants
      received a shock when they incorrectly shot a friend or missed shooting a foe; in
      the low-stress condition, participants received a vibration for an incorrect
      decision. We characterized performance using signal detection theory to
      investigate whether a participant changed their decision criterion to avoid
      making an error. Results showed that under high-stress, participants made more
      false alarms, mistaking friends as foes, and this co-occurred with increased high
      frequency heart rate variability. Finally, we examined the relationship between
      decision making and physiology, and found that participants exhibited adaptive
      behavioral and physiological profiles under different stress levels. We interpret
      this adaptive profile as a marker of an expert's ingrained training that does not
      require top down control, suggesting a way that expert training in high-stress
      environments helps to buffer negative impacts of stress on performance.

PMID- 29580905
TI  - [Management of epilepsia in older].
AB  - Epilepsy increases in frequency with age, above 60, with consequences in terms of
      independence. Stroke and dementia are the most frequent etiologies. Clinical
      diagnostic of epileptic seizure is challenging at this age, and a clinical
      algorithm is proposed. Sleep EEG during one hour seems to be the most useful
      exam. Interictal and critical discharges can be seen during sleep in dementia ;
      relation between hyperexcitability and evolution of cognition has to be precised
      in this pathology. In a therapeutical point of view, it is necessary to bear in
      mind the pharmacological consequences of aging, polytherapies, and the frequency
      of adverse events in this age group. Two molecules, lamotrigine and levetiracetam
      are recommended as first line treatment. Pronostic is good, as the majority of
      patients are seizure-free in monotherapy.

PMID- 29580906
TI  - Post-traumatic psychiatric disorders: PTSD is not the only diagnosis.
AB  - Traumatic events and their consequences are often hidden or minimised by patients
      for reasons linked to the post-traumatic stress disorder itself
      (inexpressibility, shame, depressive thoughts, fear of stigmatisation, etc.).
      Although post-traumatic stress disorder (PTSD) remains the most widely known
      disorder, chronic post-traumatic psychiatric disorders are many and varied. After
      a trauma, the practitioner has to check for the different clinical forms of post
      traumatic psychological consequences: PTSD is not the only diagnosis. Based on
      our own clinical experience compared to the international literature, we think
      necessary to build a didactic classification describing chronic post-traumatic
      symptoms and syndromes. Post traumatic depressions and bereavement lead to high
      risk of suicidal crisis and self-harm behaviours. Re-experiencing are felt with
      anxiety, hyper arousal increases anxious reactivity, and avoidance strategies
      increase anticipatory anxiety, indicating post-traumatic anxiety disorders
      (agoraphobia, specific phobia, obsessive compulsive disorder, separation anxiety,
      social phobia). Characterising an often-severe clinical picture, the co
      occurrence of post-traumatic and chronic psychotic symptoms is not unusual (post
      traumatic schizophrenia, post-traumatic depression with mood-congruent psychotic
      features, non-schizophrenic post-traumatic psychotic disorder, and bipolar
      reaction to trauma). A physical injury occurring at the same time as a traumatic
      exposure increases the risk of developing post-traumatic stress disorder later
      which, in turn, afflicts the subjective perception of the physical health
      (development of somatoform and psychosomatic disorders, comorbidity with a post
      concussion syndrome). The trauma may cause a rupture in the biography of a
      person, also in his/her internal physiological functioning as in his/her social
      activities (impacts of instinctive functions and behaviours, personality changes,
      and adjustment difficulties on professional and personal life). Although a
      nomenclature is necessary for semiological descriptions, a thorough analysis of
      the patient's general psychological functioning must also be conducted.

PMID- 29580907
TI  - [Subcutaneous emphysema complicating post-traumatic pneumoperitoneum: A rare and
      misleading complication].

PMID- 29580908
TI  - [Extracorporeal life support and heart-lung transplant in children].
AB  - Extracorporeal life support and heart and/or lung transplant are the last resort
      in children with end-stage cardiac and/or pulmonary failure and short-term life
      threaten. Currently, circulatory support is used as a bridge to recovery or as a
      bridge to transplant but not as a destination therapy. The Excor Berlin Heart is
      the long-lasting external pneumatic ventricular assist system that is currently
      available from infancy to adulthood. Long-term prognosis after pediatric cardiac
      and/or pulmonary transplant is conditioned by the occurrence of graft failure,
      coronary disease of the cardiac graft, viral infections and bronchiolitis
      obliterans of the pulmonary graft, the incidence of which increase with time. The
      scarcity of grafts and the risk of acute rejection due to lack of compliance with
      immunosuppressive treatment require the transplant specialized teams to choose
      the best candidates according to psychosocial and biological criteria. The next
      expected developments concern mainly long-term ventricular assistance with
      systems that allow for greater autonomy and a return to the child's home.

PMID- 29580909
TI  - [Ocular toxoplasmosis in an immunocompetent].

PMID- 29580910
TI  - [Neurobiological bases of alcohol addiction].
AB  - Alcohol interacts with numerous neurotransmission systems and particularly
      glutamatergic NMDA receptors and gabaergic GABAA receptors. Binge drinking
      induces both cerebral damages and cognitive deficits. Alcohol addiction is
      associated with an increase in the activation threshold of dopaminegic neurons
      and with a negative emotional state. Alcohol addiction is associated with a
      deficit in inhibitory control and an increase in motivation to drink alcohol.
      Environemental cues associated with alcohol trigger drinking desire and can
      induce relapse. Alcohol disturbs synaptic plasticity phenomena within the brain
      reward system.

PMID- 29580911
TI  - [A simple flatfoot of the child?]

PMID- 29580912
TI  - Usefulness of pharmacokinetic/efficacy analysis of an investigational kisspeptin
      analog, TAK-448, in quantitatively evaluating anti-tumor growth effect in the rat
      VCaP androgen-sensitive prostate cancer model.
AB  - TAK-448 is a kisspeptin analog with improved in vivo potency. In our previous
      studies in the rat JDCaP prostate cancer model, TAK-448 showed more rapid and
      profound reductions in plasma testosterone (T) and prostate-specific antigen
      (PSA, a biomarker of prostate tumor growth) levels than the gonadotropin
      releasing hormone (GnRH) analog leuprolide (TAP-144); however, its effects on
      tumor volume and subsequent tumor recurrence have not been elucidated fully. To
      overcome these challenges, we established the rat VCaP subcutaneous xenograft
      model replicating both the androgen-sensitive and castration-resistant phases of
      prostate cancer, and we performed pharmacokinetic/efficacy (PK/E) correlation
      analyses to compare the overall anti-tumor growth effects of TAK-448 to those of
      TAP-144. Our approach demonstrated TAK-448 had greater anti-tumor growth
      potential, including in the castration-resistant phase, than TAP-144 in this rat
      VCaP model. TAK-448 treatment was associated with a reduction in intra-tumoral
      dihydrotestosterone levels, which might explain its superior anti-tumor activity.
      Thus, our PK/E analysis was effective at providing new insights into the
      therapeutic efficacy of TAK-448 as a novel ADT agent in our rat VCaP model.

PMID- 29580913
TI  - Pulsus alternans: An ominous sign.

PMID- 29580914
TI  - [Postoperative conduction disorder in the context of a sudden right coronary
      thrombosis].

PMID- 29580915
TI  - [Tricuspid valve endocarditis in a non-drug-addicted patient with no prior
      predisposing cardiopathy].

PMID- 29580916
TI  - Influences on Intentions to Place Long-Acting Reversible Contraceptives: A Pilot
      Study Comparing According to Provider Specialty in Ohio.
AB  - STUDY OBJECTIVE: According to the American Academy of Pediatrics, pediatricians
      are to counsel and provide long-acting reversible contraceptives (LARCs) as first
      line of defense contraceptives because they are the most effective. We wanted to
      explore positive influences on LARC placement for pediatricians, particularly
      compared with providers in other specialties who care for women. DESIGN: Survey
      methods with data analyzed using analyses of variance and general linear models
      in statistical software SPSS version 24.0 (IBM Corp). SETTING: Online survey.
      PARTICIPANTS: Participants were 224 providers across the state of Ohio who
      specialize in family medicine (51.8%), obstetrics/gynecology (17.9%), pediatrics
      (16.5%), and internal medicine (13.8%). Most of the sample was female (50.9%) and
      Caucasian (74.6%). The most frequent provider types were Doctors of Osteopathic
      Medicine (42.0%), followed by Doctors of Medicine (37.9%), and Certified Nurse
      Practitioners (8.5%). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Attitudes about
      LARCs, perceived norms about placing LARCs, perceived behavioral control over
      placing LARCs, intentions to place LARCs. RESULTS: Means for all of the variables
      (attitudes, perceived norms, perceived behavioral control, and intentions to
      place) differed according to provider specialty. A pattern emerged across these
      variables in which internal medicine and pediatric practitioners reported lower
      attitudes, perceived norms, perceived behavioral control, and intentions to place
      LARCs than family medicine and obstetrics/gynecology practitioners, in that
      order. CONCLUSION: To increase positive attitudes and perceived norms about
      LARCs, professional organizations should increase communication to providers
      about the importance and expectations to place, counsel about, and facilitate
      placement of LARCs, and medical schooling can improve LARC counseling and
      procedural training to medical students, interns, and residents. Because
      perceived behavioral control is linked to intentions to place LARCs, perhaps
      providers would feel more confident to place them if they had more deliberate
      training. For pediatricians in particular, perhaps encouraging those who do not
      currently provide LARC methods to begin with training in implant placement would
      be a way to capitalize on their more favorable attitudes about implants. For
      pediatricians who do not feel comfortable providing device placement themselves,
      other strategies should be encouraged to facilitate provision of LARCs.

PMID- 29580917
TI  - Comparison of Parental and Adolescent Views on the Confidential Interview and
      Adolescent Health Risk Behaviors within the Gynecologic Setting.
AB  - STUDY OBJECTIVE: To explore parental and adolescent views on the confidential
      interview in the gynecologic setting and compare adolescent reported risk-taking
      behaviors with parental perception. DESIGN: Anonymous surveys were administered
      separately to parents/guardians and adolescents between the ages of 11 and 17
      years. Information pertaining to the patient's Tanner stage and reason for visit
      was obtained from the provider. This first phase served as the usual care group.
      In the second phase of the study, surveys were again distributed after a brief
      educational intervention. Linear regression analysis, Wilcoxon rank sum test, and
      Fisher exact test were used where appropriate. SETTING AND PARTICIPANTS:
      Pediatric and adolescent gynecology clinics in 2 tertiary hospitals.
      INTERVENTIONS: Brief educational handout on key concepts of the confidential
      interview. MAIN OUTCOME MEASURES: Parental perception of the confidential
      interview and adolescent risk-taking behaviors. RESULTS: A total of 248 surveys
      were included in the final analysis, which accounts for 62 adolescent and
      parent/guardian pairs in each group. Most parents and adolescents reported
      perceived benefit to the confidential interview. However, parents were less
      likely to rate benefits of private time specifically for their own adolescent and
      less than half of the parents believed that adolescents should have access to
      private time in the gynecologic setting. Parents/guardians as well as adolescents
      feared that the confidential interview would limit the parent's ability to take
      part in decision-making. The low support for confidential time for their
      adolescent was not different in the usual care group compared with the
      intervention group, although there was a trend toward parental acceptance with
      increased adolescent age. Adolescents were consistently more likely to report
      more risk-taking behaviors than their parents perceived. CONCLUSION: There is a
      discord between parental perception and adolescent reports of risk-taking
      behaviors. This is coupled with a lack of understanding or comfort regarding the
      benefits of the confidential interview among parents and adolescents who present
      for gynecologic care. A short educational intervention had only a modest effect
      on parental perceptions regarding the confidential interview.

PMID- 29580918
TI  - PGC-1alpha sparks the fire of neuroprotection against neurodegenerative
      disorders.
AB  - Recently, growing evidence has demonstrated that peroxisome proliferator
      activated receptor gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) is a
      superior transcriptional regulator that acts via controlling the expression of
      anti-oxidant enzymes and uncoupling proteins and inducing mitochondrial
      biogenesis, which plays a beneficial part in the central nervous system (CNS).
      Given the significance of PGC-1alpha, we summarize the current literature on the
      molecular mechanisms and roles of PGC-1alpha in the CNS. Thus, in this review, we
      first briefly introduce the basic characteristics regarding PGC-1alpha. We then
      depict some of its important cerebral functions and discuss upstream modulators,
      partners, and downstream effectors of the PGC-1alpha signaling pathway. Finally,
      we highlight recent progress in research on the involvement of PGC-1alpha in
      certain major neurodegenerative disorders (NDDs), including Alzheimer's disease,
      Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.
      Collectively, the data presented here may be useful for supporting the future
      potential of PGC-1alpha as a therapeutic target.

PMID- 29580919
TI  - Sirtuins in mitochondrial stress: Indispensable helpers behind the scenes.
AB  - Mitochondria play an essential part in guaranteeing normal cellular physiological
      functions through providing ATP and participating in diverse processes and
      signaling pathways. Recently, more and more studies have revealed the vital roles
      of mitochondria in coping with stressors in the aging process, metabolic
      disturbances and neurological disorders. Mitochondrial stress responses,
      including the mitochondrial unfolded protein response (UPRmt), antioxidant
      defense, mitochondrial fission, mitochondrial fusion and mitophagy, are induced
      to maintain cellular integrity in response to stress. The sirtuin family, a group
      of NAD+-dependent deacetylases, has been the focus of much attention in recent
      years for their multiple regulatory functions, especially in aging and
      metabolism. Recent reports validated the significant link between mitochondrial
      stress responses and the sirtuin family, which may help to elucidate the
      pathogenesis and therapies for diseases such as Alzheimer's disease or
      Parkinson's disease. This review will summarize recent related studies and
      illuminate the interplay between sirtuins and mitochondrial stress.

PMID- 29580920
TI  - Beyond ROS clearance: Peroxiredoxins in stress signaling and aging.
AB  - Antioxidants were long predicted to have lifespan-promoting effects, but in
      general this prediction has not been well supported. While some antioxidants do
      seem to have a clear effect on longevity, this may not be primarily as a result
      of their role in the removal of reactive oxygen species, but rather mediated by
      other mechanisms such as the modulation of intracellular signaling. In this
      review we discuss peroxiredoxins, a class of proteinaceous antioxidants with
      redox signaling and chaperone functions, and their involvement in regulating
      longevity and stress resistance. Peroxiredoxins have a clear role in the
      regulation of lifespan and survival of many model organisms, including the mouse,
      Caenorhabditis elegans and Drosophila melanogaster. Recent research on
      peroxiredoxins - in these models and beyond - has revealed surprising new
      insights regarding the interplay between peroxiredoxins and longevity signaling,
      which will be discussed here in detail. As redox signaling is emerging as a
      potentially important player in the regulation of longevity and aging, increased
      knowledge of these fascinating antioxidants and their mode(s) of action is
      paramount.

PMID- 29580921
TI  - Potential role for Ext1-dependent heparan sulfate in regulating P311 gene
      expression in A549 carcinoma cells.
AB  - BACKGROUND: Exostosin-1 (EXT1), a member of the EXT protein family, is
      indispensable for synthesis of heparan sulfate (HS) chains that bind to and
      modulate the signaling efficiency of numerous growth factor activities. We have
      previously shown that Ext1 mutated mouse embryonic fibroblasts produce short
      sulfated HS chains which dramatically influence tumor cell behavior in a 3
      dimensional (3D) heterospheroid system composed of tumor cells and fibroblasts.
      METHODS: In this study, we have used both 2D co-culture and 3D heterospheroid
      models, consisting of human A549 carcinoma cells co-cultured with wild-type or
      Ext1-mutated mouse embryonic fibroblasts. RESULTS AND CONCLUSIONS: Gene
      expression profiling of differentially expressed genes in fibroblast/A549
      heterospheroids identified P311 as a gene substantially down-regulated in A549
      cells co-cultured with Ext1-mutated fibroblasts. In addition, we observed that
      the Ext1 mutants displayed reduced Tgf-beta1 mRNA levels and lower levels of
      secreted active TGF-beta protein. Re-introduction of Ext1 in the Ext1 mutant
      fibroblasts rescued the levels of Tgf-beta1 mRNA, increased the amounts of
      secreted active TGF-beta in these cells, as well as P311 mRNA levels in adjacent
      A549 cells. Accordingly, small interfering RNAs (siRNAs) against fibroblast Tgf
      beta1 reduced P311 expression in neighboring A549 tumor cells. Our data raises
      the possibility that fibroblast Ext1 levels play a role in P311 expression in
      A549/fibroblast co-culture through TGF-beta1. GENERAL SIGNIFICANCE: This study
      considers a possible novel mechanism of Ext1-regulated heparan sulfate structure
      in modifying tumor-stroma interactions through altering stromal tgf-beta1
      expression.

PMID- 29580922
TI  - Characteristic glycopeptides associated with extreme human longevity identified
      through plasma glycoproteomics.
AB  - BACKGROUND: Glycosylation is highly susceptible to changes of the physiological
      conditions, and accordingly, is a potential biomarker associated with several
      diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years)
      are thought to be a model of human longevity. Thus, we performed glycoproteomics
      using plasma samples of SSCs, and identified proteins and conjugated N-glycans
      that are characteristic of extreme human longevity. METHODS: Plasma proteins from
      Japanese semi-supercentenarians (SSCs, 106-109 years), aged controls (70-88
      years), and young controls (20-38 years) were analysed by using lectin
      microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios
      of glycopeptides to corresponding normalising peptides were subjected to
      orthogonal projections to latent structures discriminant analysis (OPLS-DA).
      Furthermore, plasma levels of clinical biomarkers were measured. RESULTS: We
      found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of
      which protein binding were characteristically increased in SSCs. Peak area ratios
      of ECA-enriched glycopeptides were successfully discriminated between SSCs and
      controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans
      of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated
      glycans of haptoglobin are a potential biomarker of several diseases, such as
      hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs
      analysed here did not suffer from these diseases. CONCLUSIONS: Tri-antennary and
      sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant
      in SSCs and characteristic of extreme human longevity. GENERAL SIGNIFICANCE: We
      found abundant glycans in SSCs, which may be associated with human longevity.

PMID- 29580924
TI  - Electrical-biological hybrid system for CO2 reduction.
AB  - Here we have developed an electrochemical-biological hybrid system to fix CO2.
      Natural biological CO2 fixation processes are relatively slow. To increase the
      speed of fixation we applied electrocatalysts to reduce CO2 to formate. We chose
      a user-friendly organism, Escherichia coli, as host. Overall, the newly
      constructed CO2 and formate fixation pathway converts two formate and one CO2 to
      one pyruvate via glycine and L-serine in E. coli. First, one formate and one CO2
      are converted to one glycine. Second, L-serine is produced from one glycine and
      one formate. Lastly, L-serine is converted to pyruvate. E. coli's genetic
      tractability allowed us to balance various parameters of the pathway. The carbon
      flux of the pathway was sufficient to compensate L-serine auxotrophy in the
      strain. In total, we integrated both electrocatalysis and biological systems into
      a single pot to support E. coli growth with CO2 and electricity. Results show
      promise for using this hybrid system for chemical production from CO2 and
      electricity.

PMID- 29580923
TI  - Endoglin pathway genetic variation in preeclampsia: A validation study in
      Norwegian and Latina cohorts.
AB  - OBJECTIVE: The purpose of this study was to validate our previous genetic
      association findings related to the endoglin (ENG) pathway from an American
      Caucasian preeclampsia cohort in independent preeclampsia cohorts. We also sought
      to explore the ENG pathway for new genetic associations in these independent
      cohorts. STUDY DESIGN: We used a tagging single nucleotide (tSNP) approach to
      assess genetic variability across five ENG pathway genes (ENG, TGFbeta1,
      TGFbetaR1, ALK1, and TGFbetaR2) in a Caucasian cohort from Norway (n = 77
      preeclampsia cases & n = 63 normotensive controls) and a White Hispanic cohort
      from Southern California (n = 69 preeclampsia cases & n = 106 normotensive
      controls). MAIN OUTCOME MEASURES: Univariate analyses (Chi Square, Fisher's
      Exact) and multivariate logistic regression were conducted to evaluate the
      association between tSNP genotype distributions and pregnancy outcome in each
      cohort. Logistic regression models were adjusted for maternal age at delivery,
      infant sex, parity, smoking during pregnancy, and pre-pregnancy BMI. RESULTS:
      Although we were unable to replicate our previous SNP-specific findings (ENG
      rs11792480, rs10121110; TGFbetaR2 rs6550005; p's > 0.05), we found that genetic
      variation in TGFbetaR1[ALK5] (rs6478974) and TGFbetaR2 (rs11129420, rs6802220,
      rs1155708, rs3773640, rs3773663) was significantly associated with preeclampsia
      in the Norwegian cohort and genetic variation in ALK1 (rs706819) and TGFbetaR2
      (rs9843942) was significantly associated with preeclampsia in the Latina cohort.
      CONCLUSION: Overall, our results provide further support for the involvement and
      investigation of the endoglin pathway in preeclampsia.

PMID- 29580926
TI  - 19q13.12 microdeletion syndrome fibroblasts display abnormal storage of
      cholesterol and sphingolipids in the endo-lysosomal system.
AB  - Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency
      syndrome characterized by intellectual deficiency, developmental delays, and
      neurological movement disorders. Variability in the size and interval of the
      deletions makes it difficult to attribute the complex clinical phenotype of this
      syndrome to an underlying gene(s). As an alternate approach, we examined the
      biochemical and metabolic features of fibroblasts from an affected individual to
      derive clues as to the molecular basis for the syndrome. Immunofluorescence and
      electron microscopy of affected fibroblasts revealed an abnormal endo-lysosomal
      compartment that was characterized by rapid accumulation of lysosomotropic dyes,
      elevated LAMP1 and LAMP2 expression and vacuoles containing membrane whorls,
      common features of lysosomal lipid storage disorders. The late endosomes
      lysosomes (LE/LY) of affected fibroblasts accumulated low-density lipoprotein
      cholesterol, and displayed reduced cholesterol esterification and increased de
      novo cholesterol synthesis, indicative of defective cholesterol transport to the
      endoplasmic reticulum. Affected fibroblasts also had increased ceramide and
      sphingolipid mass, altered glycosphingolipid species and accumulation of a
      fluorescent lactosylceramide probe in LE/LY. Autophagosomes also accumulated in
      affected fibroblasts because of decreased fusion with autolysosomes, a defect
      associated with other lysosomal storage diseases. Attempts to correct the
      cholesterol/sphingolipid storage defect in fibroblasts with cyclodextrin,
      sphingolipid synthesis inhibitors or by altering ion transport were unsuccessful.
      Our data show that 19q13.12 deletion fibroblasts have abnormal accumulation of
      cholesterol and sphingolipids in the endo-lysosomal system that compromises
      organelle function and could be an underlying cause of the clinical features of
      the syndrome.

PMID- 29580925
TI  - MACBETH: Multiplex automated Corynebacterium glutamicum base editing method.
AB  - CRISPR/Cas9 or Cpf1-introduced double strand break dramatically decreases
      bacterial cell survival rate, which hampers multiplex genome editing in bacteria.
      In addition, the requirement of a foreign DNA template for each target locus is
      labor demanding and may encounter more GMO related regulatory hurdle in
      industrial applications. Herein, we developed a multiplex automated
      Corynebacterium glutamicum base editing method (MACBETH) using CRISPR/Cas9 and
      activation-induced cytidine deaminase (AID), without foreign DNA templates,
      achieving single-, double-, and triple-locus editing with efficiencies up to
      100%, 87.2% and 23.3%, respectively. In addition, MACBETH was applied to generate
      a combinatorial gene inactivation library for improving glutamate production, and
      pyk&ldhA double inactivation strain was found to improve glutamate production by
      3-fold. Finally, MACBETH was automated with an integrated robotic system, which
      would enable us to generate thousands of rationally engineered strains per month
      for metabolic engineering of C. glutamicum. As a proof of concept demonstration,
      the automation platform was used to construct an arrayed genome-scale gene
      inactivation library of 94 transcription factors with 100% success rate.
      Therefore, MACBETH would be a powerful tool for multiplex and automated bacterial
      genome editing in future studies and industrial applications.

PMID- 29580927
TI  - Acrylamide applied during pregnancy causes the neurotoxic effect by lowering BDNF
      levels in the fetal brain.
AB  - OBJECTIVES: The aim of this study is to elucidate the possible mechanism of
      neurotoxic effect of acrylamide (AA) applied during pregnancy on fetal brain
      development and to show the effect of N-acetylcysteine (NAC) on AA toxicity.
      MATERIALS AND METHODS: Four groups were formed with 9 pregnant rats each as
      control (C), acrylamide (AA), N-acetylcysteine (NAC), acrylamide plus N
      acetylcysteine (AA plus NAC) groups. Caesarian section was implemented on the
      20th day of pregnancy. Malondialdehyde (MDA), reduced glutathione (GSH),
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and
      Brain-derived neurotrophic factor (BDNF) levels were analyzed and histopathologic
      examinations were performed in brain tissues of the fetuses. RESULTS: Our data
      indicated that AA caused necrotic death and hemorrhagic damages in fetal brain
      tissue with decreasing BNDF levels and increasing oxidative stress. N
      acetylcysteine prevented the toxic effects of its on fetal brain (p < 0.05).
      CONCLUSION: Our study indicated that acrylamide has toxic effects in the fetal
      brain and N-acetylcysteine prevents its toxic effect.

PMID- 29580928
TI  - Heteroexpression and biochemical characterization of a glucose-6-phosphate
      dehydrogenase from oleaginous yeast Yarrowia lipolytica.
AB  - Yarrowia lipolytica, a nonpathogenic, nonconventional, aerobic and dimorphic
      yeast, is considered an oleaginous microorganism due to its excellent ability to
      accumulate large amounts of lipids. Glucose-6-phosphate dehydrogenase (G6PD) is
      one of two key enzymes involved in the lipid accumulation in this fungi, which
      catalyzes the oxidative dehydrogenation of glucose-6-phosphate to 6
      phosphoglucono-delta-lactone with the reduction of NADP+ to NADPH. In this study,
      the full-length gene of G6PD from Y. lipolytica (YlG6PD) was cloned without
      intron and heterogeneously expressed in E. coli. Then, YlG6PD was purified and
      biochemically characterized in details. Kinetic analysis showed that YlG6PD was
      completely dependent on NADP+ and its apparent Km for NADP+ was 33.3 MUM. The
      optimal pH was 8.5 and the maximum activity was around 47.5  degrees C. Heat
      inactivation profiles revealed that it remained 50% of maximal activity after
      incubation at 48  degrees C for 20 min YlG6PD activity was competitively
      inhibited by NADPH with a Ki value of 56.04 MUM. Most of the metal ions have no
      effect on activity, but Zn2+ was a strong inhibitor. Furthermore, the
      determinants in the coenzyme specificity of YlG6PD were investigated. Kinetic
      analysis showed that the single mutant R52D completely lost the ability to
      utilize NADP+ as its coenzyme, suggesting that Arg-52 plays a decisive role in
      NADP+ binding in YlG6PD. The identification of Y. lipolytica G6PD may provide
      useful scientific information for metabolic engineering of this yeast as a model
      for bio-oil production.

PMID- 29580929
TI  - Zidovudine: A salvage therapy for mcr-1 plasmid-mediated colistin-resistant
      bacterial infections?

PMID- 29580931
TI  - Pseudomonas aeruginosa sequence type 357 with VEB extended-spectrum beta
      lactamases in the UK: relatedness and resistance.

PMID- 29580930
TI  - Which non-carbapenem antibiotics are active against extended-spectrum beta
      lactamase-producing Enterobacteriaceae?
AB  - In this study, the activity of 18 non-carbapenem antibiotics was evaluated
      against 100 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      (ESBL-Ec) and 50 ESBL-producing Klebsiella pneumoniae (ESBL-Kp) isolated from
      urinary tract infections and bacteraemia in 2016. Minimum inhibitory
      concentrations (MICs) were determined using reference methods and the
      susceptibility profiles were defined according to European Committee on
      Antimicrobial Susceptibility Testing (EUCAST) 2017 recommendations. All of the
      ESBL-Ec isolates were susceptible to ceftazidime/avibactam and a great majority
      of them were susceptible to fosfomycin (98%), piperacillin/tazobactam (97%),
      amikacin (97%) and nitrofurantoin (96%). Mecillinam, cefoxitin and
      ceftolozane/tazobactam remained active against 92%, 83% and 78% of the ESBL-Ec
      isolates, respectively. Moreover, 100%, 94% and 90% of the ESBL-Kp tested were
      susceptible to ceftazidime/avibactam, amikacin and mecillinam, respectively. This
      study showed that there are non-carbapenem options (including orally
      administrable drugs) for the treatment of all of the situations of ESBL-Ec or
      ESBL-Kp infections, with ceftazidime/avibactam being the most efficient
      alternative.

PMID- 29580932
TI  - Postradiation hypothyroidism in head and neck cancers: A Department of Veterans
      Affairs single-institution case-control dosimetry study.
AB  - We performed a case-control study to characterize the dose-volume relationship
      and other variables leading to hypothyroidism after head and neck (H&N) cancer
      radiation therapy (RT) in a homogenous Veterans Affairs (VA) population. All
      records of patients receiving RT for various H&N cancers at a single VA medical
      center between 2007 and 2013 (n = 143) were screened for post-RT thyroid
      stimulating hormone (TSH) levels (n = 77). The thyroid gland was contoured on
      each slice of the planning computed tomography scan when available (hypothyroid:
      n = 18; euthyroid > 2 years: n = 16), and dose-volume histograms based on
      physical dose and biologically equivalent dose (BED) were compared systematically
      to find the significant dose-volume thresholds that distinguish the patients who
      developed clinical hypothyroidism. Dosimetric and clinical variables were
      considered in univariate and multivariate analysis. Preirradiation prevalence of
      hypothyroidism was 8 of 143 (5.6%). After RT, 36 of 77 (47%) screened patients
      had abnormally high TSH, of which 22 of 36 (61%) had clinical hypothyroidism
      after 1.29 +/- 0.99 years. The median follow-up durations were 3.3 years and 4.7
      years for euthyroid and hypothyroid patients, respectively. Compared with the
      euthyroid cohort (n = 41), these hypothyroid patients displayed no significant
      difference in age, gender, primary tumor site, thyroid volume, hypertension,
      diabetes, or use of chemotherapy, surgery, or intensity-modulated radiation
      therapy (IMRT). They were more likely to have had stage 3 or 4 cancer than
      euthyroid patients (86.5% vs 73.2%, p = 0.01). The odds ratios of hypothyroidism
      for stage 3 + 4 cancers and V50Gy < 75% were 5.0 and 0.2, respectively (p <
      0.05). Equivalent BED threshold of V75Gy3 < 75% gave an odds ratio of 0.156 for
      developing hypothyroidism (p = 0.02). The prevalence of post-RT clinical
      hypothyroidism was relatively high for patients with H&N cancers and warrants
      routine surveillance, especially in those with higher stage malignancy. V50Gy <
      75% may be a useful guideline to avoid hypothyroidism. We also show BED data
      which could be used for unconventionally fractionated schemes, and V75Gy3 < 75%
      may be a useful guideline.

PMID- 29580933
TI  - 3D treatment planning system-Pinnacle system.
AB  - The treatment planning system is key for the success of external beam
      radiotherapy, directly impacting the quality of treatment plans and accuracy of
      dose calculation in the plans. In this article, we provided an overview of the
      Pinnacle treatment planning system for external beam planning, including 3
      dimensional (3D) conformal plans, step-shoot intensity modulated radiotherapy
      (IMRT) plans, and volumetric modulated arc therapy (VMAT) plans. We discussed
      dose calculation algorithm and other utilities, including image fusion, plan
      documentation, and adaptive planning. Based on our many years of clinical
      experience with the system, the aim of this article is to provide readers with a
      summary of this particular planning system.

PMID- 29580934
TI  - 3D treatment planning on helical tomotherapy delivery system.
AB  - The helical tomotherapy is a technologically advanced radiation dose delivery
      system designed to perform intensity-modulated radiation therapy (IMRT). It is
      mechanistically unique, based on a small 6-MV linear accelerator mounted on a
      ring gantry that rotates around the patient while the patient moves through a
      bore, ultimately yielding a helical path of radiation dose delivery. The helical
      pattern of dose delivery differentiated tomotherapy from other contemporary
      radiation therapy systems at the time of its inception. The accompanying 3
      dimensional (3D) treatment planning system has been developed to solely support
      this specific type of dose delivery system. The treatment planning system has 2
      modules identified as TomoHelical and TomoDirect to perform IMRT and conformal
      radiation therapy, respectively. The focus of this work within the scope of this
      special issue on 3D treatment planning systems is to assess the use of planning
      tools to generate treatment plans for helical tomotherapy. Clinical examples are
      used throughout to demonstrate the quality and differences of various clinical
      scenarios planned with tomotherapy.

PMID- 29580935
TI  - Seasonal Patterns of Community Participation and Mobility of Wheelchair Users
      Over an Entire Year.
AB  - OBJECTIVE: To describe how people who use wheelchairs participate and move at
      home and in the community over an entire yearlong period, including during times
      of inclement weather conditions. DESIGN: Longitudinal mixed-methods research
      study. SETTING: Urban community in Canada. PARTICIPANTS: People who use a
      wheelchair for home and community mobility (N=11). INTERVENTION: Not applicable.
      MAIN OUTCOME MEASURES: Use of a global positioning system (GPS) tracker for
      movement in community (number of trips per day), use of accelerometer for bouts
      of wheeling mobility (number of bouts per day, speed, distance, and duration),
      prompted recall interviews to identify supports and barriers to mobility and
      participation. RESULTS: More trips per day were taken during the summer (P= .03)
      and on days with no snow and temperatures above 0 degrees C. Participants reliant
      on public transportation demonstrated more weather-specific changes in their trip
      patterns. The number of daily bouts of mobility remained similar across seasons;
      total daily distance wheeled, duration, and speed were higher on summer days,
      days with no snow, and days with temperatures above 0 degrees C. A higher
      proportion of outdoor wheeling bouts occurred in summer (P=.02) and with
      temperatures above 0 degrees C (P=.03). Inaccessible public environments were the
      primary barrier to community mobility and participation; access to social
      supports and private transportation were the primary supports. CONCLUSIONS:
      Objective support is provided for the influence of various seasonal weather
      conditions on community mobility and participation for people who use a
      wheelchair. Longitudinal data collection provided a detailed understanding of the
      patterns of, and influences on, wheelchair mobility and participation within
      wheelchair users' own homes and communities.

PMID- 29580936
TI  - Safety and Feasibility of a Neuroscience Critical Care Program to Mobilize
      Patients With Primary Intracerebral Hemorrhage.
AB  - OBJECTIVE: To measure the impact of a progressive mobility program on patients
      admitted to a neurocritical critical care unit (NCCU) with intracerebral
      hemorrhage (ICH). The early mobilization of critically ill patients with
      spontaneous ICH is a challenge owing to the potential for neurologic
      deterioration and hemodynamic lability in the acute phase of injury. Patients
      admitted to the intensive care unit have been excluded from randomized trials of
      early mobilization after stroke. DESIGN: An interdisciplinary working group
      developed a formalized NCCU Mobility Algorithm that allocates patients to
      incremental passive or active mobilization pathways on the basis of level of
      consciousness and motor function. In a quasi-experimental consecutive group
      comparison, patients with ICH admitted to the NCCU were analyzed in two 6-month
      epochs, before and after rollout of the algorithm. Mobilization and safety
      endpoints were compared between epochs. SETTING: NCCU in an urban, academic
      hospital. PARTICIPANTS: Adult patients admitted to the NCCU with primary
      intracerebral hemorrhage. INTERVENTION: Progressive mobilization after stroke
      using a formalized mobility algorithm. MAIN OUTCOME MEASURES: Time to first
      mobilization. RESULTS: The 2 groups of patients with ICH (pre-algorithm rolllout,
      n=28; post-algorithm rollout, n=29) were similar on baseline characteristics.
      Patients in the postintervention group were significantly more likely to undergo
      mobilization within the first 7 days after admission (odds ratio 8.7, 95%
      confidence interval 2.1, 36.6; P=.003). No neurologic deterioration, hypotension,
      falls, or line dislodgments were reported in association with mobilization. A
      nonsignificant difference in mortality was noted before and after rollout of the
      algorithm (4% vs 24%, respectively, P=.12). CONCLUSIONS: The implementation of a
      progressive mobility algorithm was safe and associated with a higher likelihood
      of mobilization in the first week after spontaneous ICH. Research is needed to
      investigate methods and the timing for the first mobilization in critically ill
      stroke patients.

PMID- 29580937
TI  - Windmill-task as a New Quantitative and Objective Assessment for Mirror Movements
      in Unilateral Cerebral Palsy: A Pilot Study.
AB  - OBJECTIVE: To introduce the Windmill-task, a new objective assessment tool to
      quantify the presence of mirror movements (MMs) in children with unilateral
      cerebral palsy (UCP), which are typically assessed with the observation-based
      Woods and Teuber scale (W&T). DESIGN: Prospective, observational, cohort pilot
      study. SETTING: Children's hospital. PARTICIPANTS: Prospective cohort of children
      (N=23) with UCP (age range, 6-15y, mean age, 10.5+/-2.7y). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The concurrent validity of the Windmill-task
      is assessed, and the sensitivity and specificity for MM detection are compared
      between both assessments. To assess the concurrent validity, Windmill-task data
      are compared with W&T data using Spearman rank correlations (rho) for 2
      conditions: affected hand moving vs less affected hand moving. Sensitivity and
      specificity are compared by measuring the mean percentage of children being
      assessed inconsistently across both assessments. RESULTS: Outcomes of both
      assessments correlated significantly (affected hand moving: rho=.520; P=.005;
      less affected hand moving: rho=.488; P=.009). However, many children displayed
      MMs on the Windmill-task, but not on the W&T (sensitivity: affected hand moving:
      27.5%; less affected hand moving: 40.6%). Only 2 children displayed MMs on the
      W&T, but not on the Windmill-task (specificity: affected hand moving: 2.9%; less
      affected hand moving: 1.4%). CONCLUSIONS: The Windmill-task seems to be a valid
      tool to assess MMs in children with UCP and has an additional advantage of
      sensitivity to detect MMs.

PMID- 29580938
TI  - Is 25Hz enough to accurately measure a dynamic change in the ocular
      accommodation?
AB  - BACKGROUND: Accommodation is often recorded at a low sampling rate using devices
      such as autorefractors that are designed to measure the static refractive error.
      It is therefore important to determine if that resolution is sufficient to
      accurately measure the dynamic properties of accommodation. The current study
      provides both theoretical and empirical evidence on the ideal sampling rate
      necessary to measure a dynamic response. METHODS: Accommodative and
      disaccommodative step stimuli ranging from 1-3D (1D steps) were presented using a
      Badal optical system. Responses from 12 children (8-13 years) and 6 adults (20-35
      years) were recorded using a dynamic photorefractor (DPR). Fast Fourier
      transformation was applied to the unsmoothed dynamic responses including
      position, velocity and acceleration. Also, velocity and acceleration main
      sequence (MS) characteristics were compared between three photorefractor
      conditions on 3 subjects. RESULTS: The Nyquist sampling limit necessary to
      accurately estimate position, velocity and acceleration was at least 5, 10 and
      70Hz, respectively. Peak velocity and acceleration were significantly
      underestimated at a lower rate (p<0.5). However, the slope of MS remained
      invariant with sampling rate (p>0.5). CONCLUSION: Contrary to the previous
      findings, a dynamic accommodative response exhibited frequencies larger than
      10Hz. Stimulus direction and amplitude had no influence on the frequencies
      present in the dynamic response. Peak velocity and acceleration can be
      significantly underestimated when sampled at a lower rate. Taken as a whole, low
      sampling rate instruments can accurately estimate static accommodation, however,
      caution needs to be exercised when using them for dynamic accommodation.

PMID- 29580939
TI  - Non-pharmacological management of a hemodynamically significant patent ductus
      arteriosus.
AB  - The association between the patent ductus arteriosus (PDA) and neonatal
      morbidity, mortality and poor neurodevelopmental outcome in later childhood has
      been the focus of intense debate for decades. The lack of evidence supporting
      therapeutic strategies aimed at achieving PDA closure has led to the widespread
      adoption of conservative management aimed at mitigating the impact of shunt
      volume without achieving ductal closure. In this article, we review this
      management approach, describe the supportive evidence and potential complications
      associated with this strategy.

PMID- 29580940
TI  - Relationships Among Perceived Functional Capacity, Self-Efficacy, and Disability
      After Dysvascular Amputation.
AB  - BACKGROUND: Prosthesis rehabilitation after dysvascular transtibial amputation
      (TTA) is focused on optimizing functional capacity with limited emphasis on
      promoting health self-efficacy. Self-efficacy interventions decrease disability
      for people living with chronic disease, but the influence of self-efficacy on
      disability is unknown for people with dysvascular TTA. OBJECTIVES: To identify if
      self-efficacy mediates the relationship between self-reported functional capacity
      and disability after dysvascular TTA. DESIGN: Cross-sectional, secondary data
      analysis. SETTING: Outpatient rehabilitation facilities. PARTICIPANTS: Thirty
      eight men (63.6 +/- 9.1 years old) with dysvascular TTA. METHODS: Participants
      had been living with an amputation for less than 6 months and using walking as
      their primary form of locomotion using a prosthesis. The independent variable,
      functional capacity, was measured using the Prosthesis Evaluation Questionnaire
      Mobility Scale (PEQ-MS). The proposed mediator, self-efficacy, was measured with
      the Self-Efficacy of Managing Chronic Disease questionnaire (SEMCD). MAIN OUTCOME
      MEASURE: Disability was measured using the World Health Organization Disability
      Assessment Schedule 2.0 (WHODAS 2.0) questionnaire. RESULTS: The relationship
      between self-reported functional capacity and disability is partially mediated by
      self-efficacy. Relationships between WHODAS 2.0 and PEQ-MS (r = -0.61), WHODAS
      2.0 and SEMCD (r = -0.51), and PEQ-MS and SEMCD (r = 0.44) were significant (P <
      .01). Controlling for SEMCD (P = .04), the relationship between PEQ-MS and WHODAS
      2.0 remained significant (P < .01). Statistically significant mediation was
      determined by a bootstrap method for the product of coefficients (95% confidence
      interval: -2.23, -7.39). CONCLUSIONS: This study provides initial evidence that
      the relationship between self-reported functional capacity and disability is
      partially mediated by self-efficacy after dysvascular TTA. The longitudinal
      effect of self-efficacy should be further examined to identify causal pathways of
      disability after dysvascular amputation. Furthermore, additional factors
      contributing to the relationship between self-reported functional capacity and
      disability need to be identified. LEVEL OF EVIDENCE: III.

PMID- 29580941
TI  - Increased epoxyeicosatrienoic acids may be part of a protective mechanism in
      human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide
      hydrolase expression.
AB  - BACKGROUND: Previous preclinical evidence has suggested that the elevation of
      epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP)
      epoxygenases-dependent metabolism of arachidonic acid has important anti
      inflammatory effects. However, the levels of EETs and their synthetic and
      metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To
      evaluate EETs and the expression of relevant CYP isoforms and the metabolizing
      enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16
      pairs of ulcerative colitis patients' tissues and matched with adjacent non
      inflamed tissues. EETs were extracted from tissue homogenates and analyzed by
      liquid chromatography coupled with tandem mass spectrometry. RESULTS: The
      concentration of EETs was higher in ulcerative colitis tissues compared with
      matched adjacent non-inflamed tissues (1.91 +/- 0.98 ng/mg vs. 0.96 +/- 0.77
      ng/mg, mean +/- SD, P < 0.01). As shown by immunohistochemistry, sEH was present
      in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis
      tissues compared with matched adjacent non-inflamed tissues. Western blot
      analyses showed reduced sEH expression in ulcerative colitis tissues compared
      with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in
      ulcerative colitis tissues (P < 0.05). However, there was no statistically
      significant difference observed in CYP2C8 and CYP2C9 protein expression between
      them (P > 0.05). CONCLUSION: Our data suggest that the increase in EET levels may
      be part of a protective mechanism in ulcerative colitis. Furthermore, the
      concentration of EETs could be a key factor for drug therapy for ulcerative
      colitis.

PMID- 29580942
TI  - Targeting the replication stress response in cancer.
AB  - Many conventional chemotherapies used in cancer treatment exert their effect by
      inflicting DNA damage. Highly proliferative tissues, as well as tumour cells, are
      particularly vulnerable to this damage resulting in unwanted toxicities. In
      contrast, a targeted therapeutic approach has the aim of specifically eliminating
      cancer cells but with a reduced effect on healthy tissue. New therapies have been
      developed that target the replication stress response (RSR), a branch of the
      broader DNA damage response that specifically deals with interferences of the
      normal DNA replication program. Different pharmaceutical companies have developed
      inhibitors of the RSR kinases ATR, CHK1 and WEE1, which are currently at
      different phases of clinical development. Here, we review how the RSR works at
      the molecular level, what is the rationale for its targeting, and how we envisage
      its best use in the clinic, based on patient selection and combination therapies
      supported by in vitro and in vivo preclinical studies.

PMID- 29580943
TI  - Protein tyrosine kinase 7 regulates extracellular matrix integrity and
      mesenchymal intracellular RAC1 and myosin II activities during Wolffian duct
      morphogenesis.
AB  - Wolffian duct morphogenesis must be highly coordinated with its specialized
      function of providing an optimal microenvironment for sperm maturation. Without
      normal Wolffian duct morphogenesis, male infertility will result. Our previous
      study showed that mediolateral and radial intercalation of epithelial and
      mesenchymal cells respectively, were major drivers of ductal elongation and were
      regulated by protein tyrosine kinase 7 (PTK7), a member of the planar cell
      polarity (PCP) non-canonical Wnt pathway. To understand the mechanism by which
      PTK7 regulates cell rearrangement/intercalation, we investigated the integrity of
      the extracellular matrix (ECM) and the activity of intracellular cytoskeleton
      mediators following loss of Ptk7. Abnormal assembly of nephronectin, laminin, and
      collagen IV at the basement membrane and fibrosis-like deposition of fibrilla
      collagen in the interstitium were observed in Ptk7 knockout Wolffian ducts.
      Further, the activity levels of RAC1 and myosin II, two cytoskeleton mediators,
      decreased in the Ptk7 knockout mesenchyme compared to controls. In addition, in
      vitro experiments suggested that alterations of ECM and cytoskeleton mediators
      resulted in changes in Wolffian duct morphogenesis. When in-vitro-cultured
      Wolffian ducts were treated with collagenase IV, the degree of cross-linked
      fibrilla collagen was reduced, Wolffian duct elongation and coiling were
      significantly reduced, and an expanded cyst-like duct was observed. When Wolffian
      ducts were treated with RAC1 inhibitor NSC23766, mesenchymal fibrilla collagen
      was disassembled, and Wolffian duct elongation was significantly reduced. Our
      findings provide evidence that PTK7 regulates ECM integrity and the activity
      levels of RAC1 and myosin II, which in turn regulates Wolffian duct morphogenesis
      and therefore, epididymal function.

PMID- 29580944
TI  - Inhibition of anthrax lethal factor by ssDNA aptamers.
AB  - Anthrax is caused by Bacillus anthracis, a bacterium that is able to secrete the
      toxins protective antigen, edema factor and lethal factor. Due to the high level
      of secretion from the bacteria and its severe virulence, lethal factor (LF) has
      been sought as a biomarker for detecting bacterial infection and as an effective
      target to neutralize toxicity. In this study, we found three aptamers, and
      binding affinity was determined by fluorescently labeled aptamers. One of the
      aptamers exhibited high affinity, with a Kd value of 11.0 +/- 2.7 nM, along with
      low cross reactivity relative to bovine serum albumin and protective antigen. The
      therapeutic functionality of the aptamer was examined by assessing the inhibition
      of LF protease activity against a mitogen-activated protein kinase kinase. The
      aptamer appears to be an effective inhibitor of LF with an IC50 value of 15 +/-
      1.5 MUM and approximately 85% cell viability, suggesting that this aptamer
      provides a potential clue for not only development of a sensitive diagnostic
      device of B. anthracis infection but also the design of novel inhibitors of LF.

PMID- 29580945
TI  - Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in
      humans.
AB  - Grape pomace, the major byproduct of the wine and juice industry, is a relevant
      source of bioactive phenolic compounds. However, polyphenol bioavailability in
      humans is not well understood, and the inter-individual variability in the
      production of phenolic metabolites has not been comprehensively assessed to date.
      The pharmacokinetic and excretive profiles of phenolic metabolites after the
      acute administration of a drink made from red grape pomace was here investigated
      in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in
      urine and plasma, respectively. The main circulating metabolites included phenyl
      gamma-valerolactones, hydroxybenzoic acids, simple phenols,
      hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II
      conjugates. A high inter-individual variability was shown both in urine and
      plasma samples, and different patterns of circulating metabolites were unravelled
      by applying unsupervised multivariate analysis. Besides the huge variability in
      the production of microbial metabolites of colonic origin, an important
      variability was observed due to phase II conjugates. These results are of
      interest to further understand the potential health benefits of phenolic
      metabolites on individual basis.

PMID- 29580946
TI  - Research trends in flavonoids and health.
AB  - Herein we describe, based on some bibliometric data, how the field of research on
      flavonoids has evolved over the last 25 years. The number of papers on flavonoids
      has risen in an exponential manner over these years, much faster than other
      fields on food constituents. This increase appears to be related to the
      contemporary explosion of interest in healthy foods, supplements and
      nutraceuticals. It was also probably triggered by large epidemiological studies
      on fruits and vegetables, and particularly on flavonoids, consumption and
      incidence of cancer, stroke and coronary heart disease. The widely distributed
      flavonols constitute the flavonoid subgroup upon which the greatest interest has
      been focused, followed by flavanols and more recently by anthocyanidins and other
      related polyphenols such as resveratrol. Research on isoflavones rapidly emerged
      in the 1990s but plateaued in the 2000s. In the 1990s flavonoids were mainly
      considered as the active components of medicinal plants, while from 2000 onward,
      they switched to be mainly regarded as bioactive food ingredients. We envision a
      continuation in the growth of research for the coming decade focused on clearly
      demonstrating the importance of flavonoids for human health.

PMID- 29580947
TI  - A mass spectrometry approach for the identification and localization of small
      aldehyde modifications of proteins.
AB  - Lipids containing polyunsaturated fatty acids are primary targets of oxidation,
      which produces reactive short-chain aldehydes that can covalently modify
      proteins, a process called lipoxidation. Improved mass spectrometry (MS) methods
      for the analysis of these adducts in complex biological systems are needed.
      Lysozyme and human serum albumin (HSA) were used as model proteins to investigate
      lipoxidation products formed by two short-chain aldehydes, acrolein and pentanal,
      which are unsaturated and saturated aldehydes respectively. The adducts formed
      were stabilized by NaBH4 or NaBH3CN reduction and analysed by MS. Analysis of
      intact modified lysozyme showed a pentanal modification resulting from Schiff's
      base formation (+70 Da), and up to 8 acrolein adducts, all resulting from Michael
      addition (+58 Da). Analysis of tryptic digests identified specific histidine,
      cysteine and lysine residues modified in both lysozyme and HSA, and determined
      characteristic amino acid-specific fragmentations. Eight different internal
      fragment ions were found that could be used as general diagnostic ions for
      pentanal- and acrolein-modified amino acids. The combined use of intact protein
      analysis and LC-MS/MS methods provided a powerful tool for the identification and
      localization of aldehyde-protein adducts, and the diagnostic ions will facilitate
      the development of targeted MS methods for analysis of adducts in more complex
      samples.

PMID- 29580948
TI  - Tubeimoside V sensitizes human triple negative breast cancer MDA-MB-231 cells to
      anoikis via regulating caveolin-1-related signaling pathways.
AB  - Metastatic triple-negative breast cancer (TNBC) has poor outcome with
      conventional chemotherapy regimens due to its aggressive behavior. The
      acquisition of anoikis resistance, a programmed cell death process triggered by
      substratum detachment, is an important mechanism in TNBC metastasis. Therefore,
      agents that can restore the sensitivity of cancer cells to anoikis may be helpful
      for the treatment of metastatic TNBC. In this study, we investigated the
      inhibitory effect of Tubeimosides V (TBMS-V), a cyclic bisdesmoside isolated from
      the ethanol extracts of tubers of B. paniculatum., on anoikis resistance and the
      involvement of caveolin-1(CAV-1)-related signaling pathways in such process in
      MDA-MB-231 cells. The results showed that the treatment of TBMS-V could sensitize
      cancer cells to anoikis, which was associated with suppression of anchorage
      independent culture-induced CAV-1 overexpression, EGFR activation as well as
      ITGB1-FAK activation. The data from this study might contribute to providing a
      potential therapeutic target for metastatic TNBC and suggest the possibility of
      TBMS-V and its derivatives for metastatic TNBC therapy.

PMID- 29580949
TI  - LEC1 (NF-YB9) directly interacts with LEC2 to control gene expression in seed.
AB  - The LAFL transcription factors LEC2, ABI3, FUS3 and LEC1 are master regulators of
      seed development. LEC2, ABI3 and FUS3 are closely related proteins that contain a
      B3-type DNA binding domain. We have previously shown that LEC1 (a NF-YB type
      protein) can increase LEC2 and ABI3 but not FUS3 activity. Interestingly, FUS3,
      LEC2 and ABI3 contain a B2 domain, the function of which remains elusive. We
      showed that LEC1 and LEC2 partially co-localised in the nucleus of developing
      embryos. By comparing protein sequences from various species, we identified
      within the B2 domains a set of highly conserved residues (i.e. TKxxARxxRxxAxxR).
      This domain directly interacts with LEC1 in yeast. Mutations of the conserved
      amino acids of the motif in the B2 domain abolished this interaction both in
      yeast and in moss protoplasts and did not alter the nuclear localisation of LEC2
      in planta. Conversely, the mutations of key amino acids for the function of LEC1
      in planta (D86K) prevented the interaction with LEC2. These results provide
      molecular evidences for the binding of LEC1 to B2-domain containing transcription
      factors, to form heteromers, involved in the control of gene expression.

PMID- 29580950
TI  - The Value of Early Depth of Response in Predicting Long-Term Outcome in EGFR
      Mutant Lung Cancer.
AB  - INTRODUCTION: Traditionally, marked tumor shrinkage has been assumed to portend
      better outcome. We investigated whether depth of tumor response was associated
      with improved survival outcomes in advanced EGFR-mutant NCLC. METHODS: Individual
      patient data from randomized trials (EURTAC, IPASS, ENSURE, LUX-Lung 3, and LUX
      Lung 6) were used. The association of depth of response with progression-free
      survival (PFS) and overall survival was examined using landmark analyses. Depth
      of response based on radiologic assessments at 6 weeks and 12 weeks was
      calculated as the relative changes in the sum of the longest diameters of the
      target lesions from baseline. RESULTS: Of 1081 evaluable patients at 6 weeks with
      no disease progression, 71.2% achieved Response Evaluation Criteria in Solid
      Tumors response. Using a landmark analysis, EGFR-TKI was more effective than
      chemotherapy (PFS hazard ratio = 0.36, p < .0001); and was associated with
      greater mean tumor shrinkage than chemotherapy (35.1% versus 18.5%, p < .0001).
      However, there was no significant difference in the relative PFS benefit between
      treatment groups across the entire spectrum of tumor shrinkage (p = .18 for test
      of interaction between treatment and continuously measured depth of response).
      Depth of response at 6 weeks was not associated with PFS when adjusted for
      treatment effect (hazard ratio = 0.96, p = .78). Similar results were obtained
      for 12-week landmark analysis and for OS outcome. CONCLUSIONS: The PFS advantage
      of EGFR-TKI over chemotherapy in advanced EGFR mutant NCLC is not explained by
      depth of response at 6 or 12 weeks. It should not be used as a surrogate of
      benefit in future trials or routine clinical decision making.

PMID- 29580951
TI  - Modality-specific peripheral antinociceptive effects of MU-opioid agonists on
      heat and mechanical stimuli: Contribution of sigma-1 receptors.
AB  - Morphine induces peripherally MU-opioid-mediated antinociception to heat but not
      to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit MU
      opioid antinociception to mechanical stimuli, but it is unknown whether they
      modulate MU-opioid heat antinociception. We hypothesized that sigma-1 receptors
      might play a role in the modality-specific peripheral antinociceptive effects of
      morphine and other clinically relevant MU-opioid agonists. Mechanical nociception
      was assessed in mice with the paw pressure test (450 g), and heat nociception
      with the unilateral hot plate (55  degrees C) test. Local peripheral
      (intraplantar) administration of morphine, buprenorphine or oxycodone did not
      induce antinociception to mechanical stimulation but had dose-dependent
      antinociceptive effects on heat stimuli. Local sigma-1 antagonism unmasked
      peripheral antinociception by MU-opioid agonists to mechanical stimuli, but did
      not modify their effects on heat stimulation. TRPV1+ and IB4+ cells are
      segregated populations of small neurons in the dorsal root ganglia (DRG) and the
      density of sigma-1 receptors was higher in IB4+ cells than in the rest of small
      nociceptive neurons. The in vivo ablation of TRPV1-expressing neurons with
      resiniferatoxin did not alter IB4+ neurons in the DRG, mechanical nociception, or
      the effects of sigma-1 antagonism on local morphine antinociception in this type
      of stimulus. However, it impaired the responses to heat stimuli and the effect of
      local morphine on heat nociception. In conclusion, peripheral opioid
      antinociception to mechanical stimuli is limited by sigma-1 tonic inhibitory
      actions, whereas peripheral opioid antinociception to heat stimuli (produced in
      TRPV1-expressing neurons) is not. Therefore, sigma-1 receptors contribute to the
      modality-specific peripheral effects of opioid analgesics.

PMID- 29580952
TI  - Brain tissue oxygen regulation in awake and anesthetized neonates.
AB  - Inhaled general anesthetics are used commonly in adults and children, and a
      growing body of literature from animals and humans suggests that exposure to
      anesthesia at an early age can impact brain development. While the origin of
      these effects is not well understood, it is known that anesthesia can disrupt
      oxygen regulation in the brain, which is critically important for maintaining
      healthy brain function. Here we investigated how anesthesia affected brain tissue
      oxygen regulation in neonatal rabbits by comparing brain tissue oxygen and single
      unit activity in the awake and anesthetized states. We tested two common general
      anesthetics, isoflurane and sevoflurane, delivered in both air and 80% oxygen.
      Our findings show that general anesthetics can greatly increase brain tissue PO2
      in neonates, especially when combined with supplemental oxygen. Although
      isoflurane and sevoflurane belong to the same class of anesthetics, notable
      differences were observed in their effects upon neuronal activity and spontaneous
      respiration. Our findings point to the need to consider the potential effects of
      hyperoxia when supplemental oxygen is utilized, particularly in children and
      neonates.

PMID- 29580953
TI  - Effects of drugs of abuse on channelrhodopsin-2 function.
AB  - Channelrhodopsins are light activated ion channels used extensively over the past
      decade to probe the function of genetically defined neuronal populations and
      distinct neural circuits with high temporal and spatial precision. The widely
      used Channelrhodopsin-2 variant (ChR2) is an excitatory opsin that undergoes
      conformational changes in response to blue light, allowing non-selective passage
      of protons and cations across the plasma membrane thus leading to depolarization.
      In the addiction neuroscience field, opsins such as ChR2 provide a means to
      disambiguate the overlapping circuitry involved in mediating the reinforcing and
      aversive effects of drugs of abuse as well as to determine the plasticity that
      can occur in these circuits during the development of dependence. Although ChR2
      has been widely used in animal models of drug and alcohol self-administration,
      direct effects of drugs of abuse on ChR2 function may confound its use and lead
      to misinterpretation of data. As a variety of neuronal ion channels are primary
      targets of various drugs of abuse, it is critical to determine whether ChR2
      mediated currents are modulated by these drugs. In this study, we performed whole
      cell electrophysiological recordings in HEK293 cells expressing the commonly used
      ChR2(H134R) variant and examined the effects of various drugs of abuse and other
      commonly used agents on light-induced currents. We found no differences in ChR2
      mediated currents in the presence of 30 MUM nicotine, 30 MUM cocaine, 100 MUM
      methamphetamine or 3 mM toluene. Similarly, ChR2 currents were insensitive to 30
      mM ethanol but higher concentrations (100-300 mM) produced significant effects on
      the desensitization and amplitude of light-evoked currents. Tetrahydrocannabinol
      (1-10 MUM) and morphine (30-100 MUM) significantly inhibited ChR2 currents while
      the cannabinoid receptor antagonist AM-251 had no effect. The sodium channel
      blocker tetrodotoxin (5 MUM) and the generic channel blocker/contrast agent
      gadolinium chloride (10 mM) also reduced ChR2 currents while the divalent ion
      magnesium (10 mM) had no effect. Together, the results from this study highlight
      the importance of conducting appropriate control experiments when testing new
      compounds in combination with optogenetic approaches.

PMID- 29580954
TI  - Assessing "chaotic eating" using self-report and the UK Adult National Diet and
      Nutrition Survey: No association between BMI and variability in meal or snack
      timings.
AB  - Although regular meal timings are recommended for weight loss, no study has
      characterised irregularity in the timing of eating occasions or investigated
      associations with body-mass index (BMI). Here, we characterise "chaotic eating"
      as the tendency to eat at variable times of day. In two studies, we used a novel
      measure to explore the relationship between BMI and chaotic eating. In Study 1 (N
      = 98) we measured BMI and used a self-report measure to assess the usual range of
      times that meals and snacks are consumed over a seven-day period, as well as meal
      and snack frequency. A separate meal and snack 'chaotic eating index' was derived
      from the number of possible thirty-minute snack- or meal-slots, divided by the
      frequency of these eating events. After adjusting for age, gender, and dietary
      habits (Three-Factor Eating Questionnaire) we found no relationship between BMI
      and chaotic eating of meals (beta = -0.07, p = 0.73) or snacks (beta = -0.10, p =
      0.75). In Study 2, we calculated the same chaotic eating index (meals and snacks)
      using data from the UK National Diet and Nutrition Survey of adults 2000-2001
      (seven-day diet diaries; N = 1175). Again, we found little evidence that BMI is
      associated with chaotic eating of meals (beta = 0.16, p = 0.27) or snacks (beta =
      0.15, p = 0.12). Together, these results suggest that irregular eating timings do
      not promote weight gain and they challenge guidelines that recommend regularity
      in meal timings for weight loss.

PMID- 29580955
TI  - Intraepithelial corneal haemorrhage in a rigid contact lens wearer.
AB  - Intracorneal haemorrhage is a rare complication of modern contact lens wear.
      While a limited number of reports have described intracorneal haemorrhages
      (typically stromal) associated with the extended wear of soft contact lenses with
      limited oxygen permeability for the correction of aphakia, this case report
      documents the management and resolution of a significant intraepithelial corneal
      haemorrhage associated with long-term rigid contact lens wear for keratoconus and
      high myopia.

PMID- 29580956
TI  - The use of miltefosine in the management of refractory Acanthamoeba keratitis.
AB  - Acanthamoeba keratitis (AK) is a sight threatening infection most commonly
      affecting contact lens wearers. The authors report a case of intractable
      A.polyphaga and A.castellanii, with extensive intraocular spread, managed using
      oral miltefosine. A 59-year old male contact lens wearer was referred to the
      tertiary corneal service at Bristol Eye Hospital. Vision was hand movements on
      the left and 6/6 on the right. Clinical examination was consistent with left AK
      (confirmed by corneal scrape). Management included biguanide (polyhexamethylene
      biguanide (PHMB) 0.02%, later 0.06%) and diamidine (hexamidine 0.1%). Further
      treatment included imidazole (guttae voriconazole, oral posaconazole) and
      fortified biguanide (chlorhexidine 0.2%). Therapeutic PKP was performed.
      Microscopy revealed Acanthamoeba throughout host stroma. Corneal scrape and
      anterior chamber tap revealed persistent infection with Acanthamoeba.
      Intracameral voriconazole was administered twice. Clinically there was scleritis,
      with concerns regarding posterior segment involvement. There was a severe
      necrotic keratitis with almost complete corneal melt, requiring enucleation. Oral
      miltefosine was commenced to reduce the risk of transmission of Acanthamoeba
      beyond ocular structures at the time of the enucleation. Histopathological
      analysis detected A.polyphaga and A.castellanii in vitreous but not retina,
      choroid or optic nerve suggesting that infection had not progressed posteriorly
      through the ocular structures and the central nervous system was not involved.
      The use of miltefosine as a component of combination anti-parasitic therapy is
      associated with long-term survival in cases of Acanthamoeba infection of the
      central nervous system. This case reports its first systemic use in the United
      Kingdom in a case of severe intractable AK with intraocular spread.

PMID- 29580957
TI  - Alamandine injected into the paraventricular nucleus increases blood pressure and
      sympathetic activation in spontaneously hypertensive rats.
AB  - Alamandine is a newly discovered new component of the renin-angiotensin (Ang)
      system (RAS) that has been shown to exert vasoactive effects in some areas of the
      nervous system. The present study investigated whether administration of
      alamandine to the hypothalamic paraventricular nucleus (PVN) modulates blood
      pressure and sympathetic activity. Mean arterial pressure (MAP) and renal
      sympathetic nerve activity (RSNA) were recorded in anaesthetized rats. PVN
      microinjection of alamandine increased MAP and RSNA both in Wistar-Kyoto (WKY)
      rats and in spontaneously hypertensive rats (SHRs), but to a greater extent in
      SHRs. Moreover, these effects were blocked by pretreatment with alamandine
      receptor Mas-related G-protein-coupled receptor, member D (MrgD) antagonist D
      Pro7-Ang-(1-7), adenylyl cyclase (AC) inhibitor SQ22536, and protein kinase A
      (PKA) inhibitor rp-adenosine-3',5'-cyclic monophosphorothionate (Rp-cAMP).
      Treatment with D-Pro7-Ang-(1-7), SQ22536, or Rp-cAMP alone in PVN decreased MAP
      and RSNA in the SHRs. Conversely cAMP alone increased MAP and RSNA, and
      pretreatment with cAMP enhanced alamandine's effects. These results indicate that
      microinjection of alamandine into the PVN increases blood pressure and
      sympathetic outflow via MrgD and the cAMP-PKA pathway.

PMID- 29580959
TI  - Repetitive versus standard tactile stimulation of preterm infants at birth - A
      randomized controlled trial.
AB  - AIM: To evaluate the direct effect of repetitive tactile stimulation on breathing
      effort of preterm infants at birth. METHODS: This randomized controlled trial
      compared the effect of repetitive stimulation on respiratory effort during the
      first 4 min after birth with standard stimulation based on clinical indication in
      preterm infants with a gestational age of 27-32 weeks. All details of the
      stimulation performed were noted. The main study parameter measured was
      respiratory minute volume, other study parameters assessed measures of
      respiratory effort; tidal volumes, rate of rise to maximum tidal volumes,
      percentage of recruitment breaths, and oxygenation of the infant. RESULTS: There
      was no significant difference in respiratory minute volume in the repetitive
      stimulation group when compared to the standard group. Oxygen saturation was
      significantly higher (87.6 +/- 3.3% vs 81.7 +/- 8.7%, p = .01) while the amount
      of FiO2 given during transport to the NICU was lower (28.2 (22.8-35.0)% vs 33.6
      (29.4-44.1)%, p = .04). There was no significant difference in administration of
      positive pressure ventilation (52% vs 78%, p = .13), or the duration of
      ventilation (median (IQR) time 8 (0-118)s vs 35 (13-131)s, p = .23). Caregivers
      decided less often to administer caffeine in the delivery room to stimulate
      breathing in the repetitive stimulation group (10% vs 39%, p = .036). CONCLUSION:
      Although the increase in respiratory effort during repetitive stimulation did not
      reach significance, oxygenation significantly improved with a lower level of FiO2
      at transport to the NICU. Repetitive tactile stimulation could be of added value
      to improve breathing effort at birth.

PMID- 29580958
TI  - Cerebral saturation in cardiac arrest patients measured with near-infrared
      technology during pre-hospital advanced life support. Results from Copernicus I
      cohort study.
AB  - AIM: To date, monitoring options during pre-hospital advanced life support (ALS)
      are limited. Regional cerebral saturation (rSO2) may provide more information
      concerning the brain during ALS. We hypothesized that an increase in rSO2 during
      ALS in out-of hospital cardiac arrest (OHCA) patients is associated with return
      of spontaneous circulation (ROSC). METHODS: A prospective, non-randomized
      multicenter study was conducted in the pre-hospital setting of six hospitals in
      Belgium. Cerebral saturation was measured during pre-hospital ALS by a medical
      emergency team in OHCA patients. Cerebral saturation was continuously measured
      until ALS efforts were terminated or until the patient with sustained ROSC (>20
      min) arrived at the emergency department. To take the longitudinal nature of the
      data into account, a linear mixed model was used. The correlation between the
      repeated measures of a patient was handled by means of a random intercept and a
      random slope. Our primary analysis tested the association of rSO2 with ROSC.
      RESULTS: Of the 329 patients 110 (33%) achieved ROSC. First measured rSO2 was 30%
      +/- 18 in the ROSC group and 24% +/- 15 in the no-ROSC group (p = .004; mean +/-
      SD). Higher mean rSO2 values were observed in the ROSC group compared to the no
      ROSC group (41% +/- 13 versus 33% +/- 13 respectively; p < 0.001). The median
      increase in rSO2, measured from start until two minutes before ROSC, was higher
      in the ROSC group (ROSC group 17% (IQR 6-29)) than in the no-ROSC group (8% (IQR
      2-13); p < 0.001). An increase in rSO2 above 15% was associated with ROSC (OR
      4.5; 95%CI 2.747-7.415; p < 0.001). CONCLUSION: Regional cerebral saturation
      measurements can be used during pre-hospital ALS as an additional marker to
      predict ROSC. An increase of at least 15% in rSO2 during ALS is associated with a
      higher probability of ROSC.

PMID- 29580960
TI  - Prediction and risk stratification of survival in accidental hypothermia
      requiring extracorporeal life support: An individual patient data meta-analysis.
AB  - BACKGROUND: Extra-corporeal life support (ECLS) is a life-saving intervention for
      patients with hypothermia induced cardiac arrest or severe cardiovascular
      instability. However, its application is highly variable due to a paucity of data
      in the literature to guide practice. Current guidelines and recommendations are
      based on expert opinion, single case reports, and small case series. Combining
      all of the published data in a patient-level analysis can provide a robust
      assessment of the influence of patient characteristics on survival with ECLS.
      OBJECTIVE: To develop a prediction model of survival with good neurologic outcome
      for accidental hypothermia treated with ECLS. METHODS: Electronic searches of
      PubMed, EMBASE, CINAHL were conducted with a hand search of reference lists and
      major surgical and critical care conference abstracts. Studies had to report the
      use of ECLS configured with a circuit, blood pump and oxygenator with an
      integrated heat exchanger. Randomized and observational studies were eligible for
      inclusion. Non-human, non-English and review manuscripts were deemed ineligible.
      Study authors were requested to submit patient level data when aggregate or
      incomplete individual patient data was provided in a study. Survival with good
      neurologic outcome was categorized for patients to last follow-up based on the
      reported scores on the Cerebral Performance Category (1 or 2), Glasgow Outcome
      Scale (4 or 5) and Pediatric Overall Performance Category (1 or 2). A one-stage,
      individual patient data meta-analysis was performed with a mixed-effects multi
      level logistic regression model reporting odds ratio (OR) with a 95% confidence
      interval (CI). RESULTS: Data from 44 observational studies and 40 case reports (n
      = 658) were combined and analyzed to identify independent predictors of survival
      with good neurologic outcome. The survival rate with good neurologic outcome of
      the entire cohort was 40.3% (265 of 658). ECLS rewarming rate (OR: 0.93; 95% CI:
      0.88, 0.98; p = .007), female gender (OR: 2.78; 95% CI: 1.69, 4.58; p < 0.001),
      asphyxiation (OR: 0.19; 95% CI: 0.11, 0.35; p < 0.001) and serum potassium (OR:
      0.62; 95% CI: 0.53, 0.73; p < 0.001) were associated with survival with a good
      neurologic outcome. The logistic regression model demonstrated excellent
      discrimination (c-statistic: 0.849; 95% CI: 0.823, 0.875). CONCLUSIONS: The use
      of extracorporeal life support in the treatment of hypothermic cardiac arrest
      provides a favourable chance of survival with good neurologic outcome. When used
      in a weighted scoring system, asphyxiation, serum potassium and gender can help
      clinicians prognosticate the benefit of resuscitating hypothermic patients with
      ECLS.

PMID- 29580961
TI  - Childhood aggression: A synthesis of reviews and meta-analyses to reveal patterns
      and opportunities for prevention and intervention strategies.
AB  - This study provides a synthesis of meta-analyses and systematic reviews on non
      pharmacological treatments for childhood aggression. Treatments referred to
      universal prevention, selective prevention, indicated prevention, or intervention
      (Mrazek and Haggerty, 1994). Seventy-two meta-analyses and systematic reviews met
      the inclusion criteria. We describe their characteristics, effect sizes across
      types of treatments, and the effects of various moderators. For universal and
      selective prevention, effects were mostly absent or small; for indicated
      prevention and interventions, effects were mostly small or medium. Only two
      moderators had a positive effect on treatment effectiveness, namely pre-test
      levels of aggression and parental involvement. These results identified
      similarities between indicated prevention and intervention treatments, on the one
      hand, and universal prevention and selective prevention, on the other. Our
      findings suggest that research distinguishing between targets of treatments
      (i.e., factors associated with childhood aggression vs. present aggressive
      behaviors) would be promising. Moreover, to further increase effectiveness of
      treatments for childhood aggression, individual differences warrant scientific
      attention.

PMID- 29580962
TI  - Acute Changes in Electrophysiological Properties of Cortical Regular-Spiking
      Cells Following Seizures in a Rat Lithium-Pilocarpine Model.
AB  - Profound alterations in both the synaptic and intrinsic membrane properties of
      neurons that increase the neuronal network excitability are found in epileptic
      tissue. However, there are still uncertainties regarding the kind of changes in
      the intrinsic membrane properties occurring during epileptogenesis.
      Epileptogenesis is typically triggered by the initial brain-damaging insult, and
      status epilepticus (SE) is one of such insults. In the present study, we explored
      the acute changes in the intrinsic membrane properties of pyramidal cells one day
      after SE in a rat lithium-pilocarpine model. Using whole-cell patch-clamp
      recording and the dynamic-clamp technique, we investigated the properties of
      regular-spiking neurons in the entorhinal cortex (EC) and the medial prefrontal
      cortex (PFC), two areas differentially affected by SE. We found that one day
      after SE: (1) the intrinsic membrane properties of EC neurons are significantly
      altered, while the properties of PFC neurons are mostly unchanged; (2) the input
      resistance and membrane time constant of regular-spiking neurons are reduced due
      to enhanced leak current; (3) the active membrane properties of neurons are
      mostly unaffected; and (4) changes in the passive membrane properties diminish
      the intrinsic neuronal excitability. Therefore, our results suggest that the
      acute changes in the intrinsic membrane properties of entorhinal neurons
      following pilocarpine-induced SE do not contribute to network hyperexcitability.
      In contrast, at the early stage of epileptogenesis, protective homeostatic
      plasticity of intrinsic membrane properties is observed in the EC; it reduces the
      neuronal excitability in response to increased network excitability.

PMID- 29580963
TI  - Neurovascular Coupling During Visual Stimulation in Multiple Sclerosis: A MEG
      fMRI Study.
AB  - The process of neurovascular coupling ensures that increases in neuronal activity
      are fed by increases in cerebral blood flow. Evidence suggests that neurovascular
      coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain
      hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and
      altered levels of vasoactive compounds. Here, we tested the hypothesis that
      neurovascular coupling is impaired in MS. We characterized neurovascular coupling
      as the relationship between changes in neuronal oscillatory power within the
      gamma frequency band (30-80 Hz), as measured by magnetoencephalography (MEG), and
      associated hemodynamic changes (blood oxygenation level dependent, BOLD, and
      cerebral blood flow, CBF) as measured by functional MRI. We characterized these
      responses in the visual cortex in 13 MS patients and in 10 matched healthy
      controls using a reversing checkerboard stimulus at five visual contrasts. There
      were no significant group differences in visual acuity, P100 latencies, occipital
      gray matter (GM) volumes and baseline CBF. However, in the MS patients we found a
      significant reduction in peak gamma power, BOLD and CBF responses. There were no
      significant differences in neurovascular coupling between groups, in the visual
      cortex. Our results suggest that neuronal and vascular responses are altered in
      MS. Gamma power reduction could be an indicator of GM dysfunction, possibly
      mediated by GABAergic changes. Altered hemodynamic responses confirm previous
      reports of a vascular dysfunction in MS. Despite altered neuronal and vascular
      responses, neurovascular coupling appears to be preserved in MS, at least within
      the range of damage and disability studied here.

PMID- 29580964
TI  - Obstetric patients' health-related quality of life before and after intensive
      care.
AB  - BACKGROUND: Intensive care admissions during pregnancy, childbirth, and
      postpartum period are relatively well investigated. However, very little is known
      about these obstetric patients' health-related quality of life (HRQoL) before and
      after critical care. OBJECTIVE: The objective of this study was to assess
      obstetric patients' HRQoL before intensive care admission (baseline) and at 6
      months after discharge (follow-up) DESIGN: This was a retrospective database
      study. In a 5-year period, the data of all women admitted to the intensive care
      unit (ICU) during pregnancy, delivery, or up to 42 days postpartum were analysed.
      METHODS: Four multidisciplinary ICUs of Finnish University hospitals
      participated. The HRQoL was assessed using the EuroQol-5D (EQ-5D) instrument with
      utility score (EQsum) and visual analogue scale (EQ-VAS). RESULTS: A total of 283
      obstetric patients were identified from the clinical information system. Of
      these, 99 (35%) completed the EQ-5D questionnaires both at baseline and follow
      up, and 65 of them (23%) completed EQ-VAS. The comparison of patients' EQsum
      scores before intensive care admission and after discharge showed that patients'
      HRQoL remained good (0.970 vs 0.972) (max 1.0) or increased (0.788 vs 0.982) in
      80.8% of the patients. Patients reported improved overall health on the EQ-VAS at
      6 months follow-up (EQ-VAS mean, 71.86 vs 88.20; p <= 0.001) (max 100). However,
      19.2% of the patients had lower HRQoL (EQsum mean 0.987 vs 0.798) at follow-up.
      Following intensive care, 15% of the patients had more pain/discomfort, and 11%
      expressed more depression/anxiety. Multiparous patients were more likely to
      suffer from worsened depression/anxiety (p = 0.024). CONCLUSION: In the majority
      of the obstetric patients, HRQoL at 6 months follow-up remained good or had
      increased from baseline. However, nearly one-fifth of the patients had impaired
      HRQoL after discharge. Thus, intensive care management should take in to
      consideration follow-up program after intensive care of ICU-admitted obstetric
      patients.

PMID- 29580965
TI  - Designing a nurse-delivered delirium bundle: What intensive care unit staff,
      survivors, and their families think?
AB  - BACKGROUND: Implementation of quality improvement interventions can be enhanced
      by exploring the perspectives of those who will deliver and receive them. We
      designed a non-pharmacological bundle for delirium management for a feasibility
      trial, and we sought to obtain the views of intensive care unit (ICU) staff,
      survivors, and families on the barriers and facilitators to its implementation.
      OBJECTIVE: The objective of this study is to determine the barriers and
      facilitators to a multicomponent bundle for delirium management in critically ill
      patients comprising (1) education and family participation, (2) sedation
      minimisation and pain, agitation, and delirium protocol, (3) early mobilisation,
      and (4) environmental interventions for sleep, orientation, communication, and
      cognitive stimulation. METHODS: Nine focus group interviews were conducted with
      ICU staff (n = 68) in 12 UK ICUs. Three focus group interviews were conducted
      with ICU survivors (n = 12) and their family members (n = 2). Interviews were
      digitally recorded, transcribed, and thematically analysed using the Braun and
      Clarke framework. RESULTS: Overall, staff, survivors, and their families agreed
      the bundle was acceptable. Facilitating factors for delivering the bundle were
      staff and relatives' education about potential benefits and encouraging family
      presence. Facilitating factors for sedation minimisation were evening ward
      rounds, using non-verbal pain scores, and targeting sedation scores. Barriers
      identified by staff were inadequate resources, poor education, relatives'
      anxiety, safety concerns, and ICU culture. Concerns were raised about patient
      confidentiality when displaying orientation materials and managing resources for
      early mobility. Survivors cited that flexible visiting and re-establishing
      normality were important factors; and staff workload, lack of awareness, and poor
      communication were factors that needed to be considered before implementation.
      CONCLUSION: Generally, the bundle was deemed acceptable and deliverable. However,
      like any complex intervention, component adaptations will be required depending
      on resources available to the ICU; in particular, involvement of pharmacists in
      the ward round and physiotherapists in mobilising intubated patients.

PMID- 29580966
TI  - Hand hygiene compliance and behavioural determinants in a paediatric intensive
      care unit: An observational study.
AB  - BACKGROUND: Hand hygiene is considered the single most effective means of
      reducing healthcare-associated infections, but improving and sustaining hand
      hygiene compliance remains a great challenge. OBJECTIVES: To compare hand hygiene
      compliance before and after interventions to promote adherence in a paediatric
      intensive care unit (PICU) and to identify predictors of intention to perform the
      behaviour "hand hygiene during patient care in the PICU". METHODS: A before and
      after study was conducted in three phases. Based on the World Health Organization
      guideline for hand hygiene compliance monitoring, 1261 hand hygiene opportunities
      were directly observed during routine patient care by two observers
      simultaneously, in a nine-bed PICU in Brazil, before and after infrastructure and
      educational interventions. To identify predictors of healthcare professionals'
      intention to perform the behaviour hand hygiene during patient care, a data
      collection instrument was designed based on the Theory of Planned Behaviour.
      Statistical analyses were undertaken using Chi-square test or the Fisher's exact
      test and regression analysis. A significance level of 5% (p < 0.05) was applied
      to all analyses. RESULTS: The hand hygiene compliance rate increased
      significantly from 27.3% in the "pre-intervention phase" to 33.1% in "phase 1
      post-intervention," to 37.0% in "phase 2-post-intervention" (p = .010). Perceived
      social pressure (p = .026) was a determinant factor of intention to perform the
      behaviour. CONCLUSIONS: Hand hygiene compliance raised significantly after
      infrastructure, educational, and performance feedback interventions. However,
      despite the significant effect of the implemented interventions, the overall hand
      hygiene compliance rate was low. Perceived social pressure characterised a
      determinant factor of intention to perform the behaviour "hand hygiene during
      patient care in the PICU", reinforcing the need for behaviour determinants
      analysis when designing promotional interventions.

PMID- 29580967
TI  - Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2
      measurements for estimation of deoxygenated blood volume and hemoglobin oxygen
      saturation.
AB  - Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of
      hemodynamic and metabolic properties of the brain in the baseline state, provides
      spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen
      saturation (HbO2) by means of an analytical model for the temporal evolution of
      free-induction-decay signals in the extravascular compartment. However, mutual
      coupling between DBV and HbO2 in the signal model results in considerable
      estimation uncertainty precluding achievement of a unique set of solutions. To
      address this problem, we developed an interleaved qBOLD method (iqBOLD) that
      combines extravascular R2' and intravascular R2 mapping techniques so as to
      obtain prior knowledge for the two unknown parameters. To achieve these goals,
      asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were
      interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF
      signals were suppressed to produce reliable estimates for cerebral venous blood
      volume fraction (CBVv) as well as venous blood R2 (to yield HbO2). Parameter maps
      derived from the VSSL module were employed to initialize DBV and HbO2 in the
      qBOLD processing. Numerical simulations and in vivo experiments at 3 T were
      performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD
      method. Data obtained in eight healthy subjects yielded plausible values
      averaging 60.1 +/- 3.3% for HbO2 and 3.1 +/- 0.5 and 2.0 +/- 0.4% for DBV in gray
      and white matter, respectively. Furthermore, the results show that prior
      estimates of CBVv and HbO2 from the VSSL component enhance the solution stability
      in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a
      promising alternative to the conventional technique for quantifying
      neurometabolic parameters.

PMID- 29580969
TI  - Unconventional secretion of transmembrane proteins.
AB  - Over the past 20 years it has become evident that eukaryotic cells utilize both
      conventional and unconventional pathways to deliver proteins to their target
      sites. Most proteins with a signal peptide and/or a transmembrane domain are
      conventionally transported through the endoplasmic reticulum to the Golgi
      apparatus and then to the plasma membrane. However, an increasing number of both
      soluble cargos (Type I, II, and III) and integral membrane proteins (Type IV)
      have been found to reach the plasma membrane via unconventional protein secretion
      (UPS) pathways that bypass the Golgi apparatus under certain conditions, such as
      cellular stress or development. Well-known examples of transmembrane proteins
      that undergo Type IV UPS pathways are position-specific antigen subunit alpha 1
      integrin, cystic fibrosis transmembrane conductance regulator, myeloproliferative
      leukemia virus oncogene, and pendrin. Although we collectively refer to all Golgi
      bypassing routes as UPS, individual trafficking pathways are diverse compared to
      the conventional pathways, and the molecular mechanisms of UPS pathways are not
      yet completely defined. This review summarizes the intracellular trafficking
      pathways of UPS cargo proteins, particularly those with transmembrane domains,
      and discusses the molecular machinery involved in the UPS of transmembrane
      proteins.

PMID- 29580968
TI  - Correlation of neural activity with behavioral kinematics reveals distinct
      sensory encoding and evidence accumulation processes during active tactile
      sensing.
AB  - Many real-world decisions rely on active sensing, a dynamic process for directing
      our sensors (e.g. eyes or fingers) across a stimulus to maximize information
      gain. Though ecologically pervasive, limited work has focused on identifying
      neural correlates of the active sensing process. In tactile perception, we often
      make decisions about an object/surface by actively exploring its shape/texture.
      Here we investigate the neural correlates of active tactile decision-making by
      simultaneously measuring electroencephalography (EEG) and finger kinematics while
      subjects interrogated a haptic surface to make perceptual judgments. Since
      sensorimotor behavior underlies decision formation in active sensing tasks, we
      hypothesized that the neural correlates of decision-related processes would be
      detectable by relating active sensing to neural activity. Novel brain-behavior
      correlation analysis revealed that three distinct EEG components, localizing to
      right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and
      supplementary motor area (SMA), respectively, were coupled with active sensing as
      their activity significantly correlated with finger kinematics. To probe the
      functional role of these components, we fit their single-trial-couplings to
      decision-making performance using a hierarchical-drift-diffusion-model (HDDM),
      revealing that the LOC modulated the encoding of the tactile stimulus whereas the
      MFG predicted the rate of information integration towards a choice.
      Interestingly, the MFG disappeared from components uncovered from control
      subjects performing active sensing but not required to make perceptual decisions.
      By uncovering the neural correlates of distinct stimulus encoding and evidence
      accumulation processes, this study delineated, for the first time, the functional
      role of cortical areas in active tactile decision-making.

PMID- 29580970
TI  - Role of autophagy in IL-1beta export and release from cells.
AB  - The autophagy pathway known also as macroautophagy (herein referred to as
      autophagy) is characterized by the formation of double-membrane organelles that
      capture cytosolic material. Based on pathway termination alternatives, autophagy
      has been divided into degradative and secretory. During degradative autophagy,
      autophagosomes typically fuse with lysosomes upon which the sequestered material
      is degraded. During secretory autophagy, instead of degradation the sequestered
      cargo is subjected to active secretion or passive release. In this review, we
      focus on the mechanisms of secretion/passive release of the potent pro
      inflammatory cytokine IL-1beta, as a prototypical leaderless cytosolic protein
      cargo studied in the context of secretory autophagy.

PMID- 29580972
TI  - Making reliable negative predictions of human skin sensitisation using an in
      silico fragmentation approach.
AB  - A previously published fragmentation method for making reliable negative in
      silico predictions has been applied to the problem of predicting skin
      sensitisation in humans, making use of a dataset of over 2750 chemicals with
      publicly available skin sensitisation data from 18 in vivo assays. An assay
      hierarchy was designed to enable the classification of chemicals within this
      dataset as either sensitisers or non-sensitisers where data from more than one in
      vivo test was available. The negative prediction approach was validated
      internally, using a 5-fold cross-validation, and externally, against a
      proprietary dataset of approximately 1000 chemicals with in vivo reference data
      shared by members of the pharmaceutical, nutritional, and personal care
      industries. The negative predictivity for this proprietary dataset was high in
      all cases (>75%), and the model was also able to identify structural features
      that resulted in a lower accuracy or a higher uncertainty in the negative
      prediction, termed misclassified and unclassified features respectively. These
      features could serve as an aid for further expert assessment of the negative in
      silico prediction.

PMID- 29580971
TI  - Retroviral Gag protein-RNA interactions: Implications for specific genomic RNA
      packaging and virion assembly.
AB  - Retroviral Gag proteins are responsible for coordinating many aspects of virion
      assembly. Gag possesses two distinct nucleic acid binding domains, matrix (MA)
      and nucleocapsid (NC). One of the critical functions of Gag is to specifically
      recognize, bind, and package the retroviral genomic RNA (gRNA) into assembling
      virions. Gag interactions with cellular RNAs have also been shown to regulate
      aspects of assembly. Recent results have shed light on the role of MA and NC
      domain interactions with nucleic acids, and how they jointly function to ensure
      packaging of the retroviral gRNA. Here, we will review the literature regarding
      RNA interactions with NC, MA, as well as overall mechanisms employed by Gag to
      interact with RNA. The discussion focuses on human immunodeficiency virus type-1,
      but other retroviruses will also be discussed. A model is presented combining all
      of the available data summarizing the various factors and layers of selection Gag
      employs to ensure specific gRNA packaging and correct virion assembly.

PMID- 29580973
TI  - A pre-clinical safety study of PEGylated recombinant human endostatin (M2ES) in
      Sprague Dawley rats.
AB  - PEGylated recombinant human endostatin (M2ES) exhibited prolonged serum half-life
      and enhanced antitumor activity when compared with endostatin. A pre-clinical
      study was performed to evaluate the safety of M2ES in rats. After intravenous
      (IV) infusions of M2ES at a dose level of 3, 15 and 75 mg/kg in Sprague Dawley
      (SD) rats, M2ES was well tolerated in animals, with no observable changes in
      clinical observation, body weight, food consumption, urine analysis, hematology
      and serum biochemical analysis. The increase of kidney weights, and slight to
      severe vacuolation and necrosis of proximal tubule epithelial cells in kidney
      were observed in 15 and 75 mg/kg M2ES groups, but this adverse-effect was
      reversible. In summary, the major toxicity target organ of M2ES might be kidney,
      and the no observed adverse effect level (NOAEL) of M2ES in rats was 3 mg/kg in
      this study. These pre-clinical safety data contribute to the initiation of the
      ongoing clinical study.

PMID- 29580974
TI  - The safety of green tea and green tea extract consumption in adults - Results of
      a systematic review.
AB  - A systematic review of published toxicology and human intervention studies was
      performed to characterize potential hazards associated with consumption of green
      tea and its preparations. A review of toxicological evidence from laboratory
      studies revealed the liver as the target organ and hepatotoxicity as the critical
      effect, which was strongly associated with certain dosing conditions (e.g. bolus
      dose via gavage, fasting), and positively correlated with total catechin and
      epigallocatechingallate (EGCG) content. A review of adverse event (AE) data from
      159 human intervention studies yielded findings consistent with toxicological
      evidence in that a limited range of concentrated, catechin-rich green tea
      preparations resulted in hepatic AEs in a dose-dependent manner when ingested in
      large bolus doses, but not when consumed as brewed tea or extracts in beverages
      or as part of food. Toxico- and pharmacokinetic evidence further suggests
      internal dose of catechins is a key determinant in the occurrence and severity of
      hepatotoxicity. A safe intake level of 338 mg EGCG/day for adults was derived
      from toxicological and human safety data for tea preparations ingested as a solid
      bolus dose. An Observed Safe Level (OSL) of 704 mg EGCG/day might be considered
      for tea preparations in beverage form based on human AE data.

PMID- 29580975
TI  - Argon Cold Plasma-A Novel Tool to Treat Therapy-resistant Corneal Infections.
AB  - PURPOSE: To test whether therapy-resistant corneal infections can be successfully
      treated with argon cold plasma to reduce or eliminate pathogen microorganisms
      without affecting corneal cell viability. DESIGN: First-in-human case series and
      experimental study. METHODS: Cold plasma effects on viability of primary human
      corneal limbal epithelial cells were studied using exposure times from 0.5 to 10
      minutes (metabolic activity, oxidative stress, apoptosis). Disinfective potential
      of cold plasma was tested against common pathogens (Staphylococcus aureus,
      Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida
      albicans) on culture medium and evaluated by counting colony-forming units and
      optical density measurements, as well as against S aureus in a human cornea
      infection model. Additionally, in a first-in-human trial 4 patients with therapy
      resistant corneal ulcers were treated to evaluate the clinical potential of cold
      plasma. RESULTS: Cells treated for 0.5-5 minutes completely recovered within 24
      hours without changes in morphology; only 10-minute treatment impaired the cells
      permanently. No evident oxidative stress, apoptosis, or damage to the corneal
      structure could be found. All pathogens were susceptible to cold plasma
      treatments, with different levels of sensitivity. The condition of all 4 patients
      significantly improved after cold plasma treatment combined with antibiotic
      therapy. CONCLUSIONS: Our results indicate that argon cold plasma treatment
      reduces or eliminates common pathogens without impairing corneal epithelial cells
      in vitro, ex vivo, and in direct application on patients' eyes. We conclude that
      argon cold plasma therapy offers a potential supplement or alternative therapy
      for therapy-resistant corneal infections. A larger, comparative study is
      necessary to further confirm these findings.

PMID- 29580976
TI  - Inter-eye Asymmetry of Optical Coherence Tomography Angiography Vessel Density in
      Bilateral Glaucoma, Glaucoma Suspect, and Healthy Eyes.
AB  - PURPOSE: To investigate inter-eye retinal vessel density asymmetry in healthy,
      glaucoma suspect, and mild-to-moderate glaucoma subjects, and its potential
      utility for early detection of glaucomatous damage. DESIGN: Cross-sectional
      study. METHODS: In 153 subjects including 55 healthy, 32 glaucoma suspect, and 66
      glaucoma subjects enrolled in the Diagnostic Innovations in Glaucoma Study
      (DIGS), vessel density was obtained from optical coherence tomography angiography
      (OCT-A) macular and optic nerve head scans. Thickness of peripapillary retinal
      nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) was measured
      with spectral-domain optical coherence tomography (SD-OCT) scans. Inter-eye
      asymmetry was calculated by taking the absolute value of difference in vessel
      density and thickness between the right and left eyes. RESULTS: Inter-eye retinal
      vessel density asymmetry parameters were significantly different among the 3
      groups. Glaucoma suspects had significantly higher peripapillary and macular
      inter-eye vessel density asymmetries compared to healthy groups in univariate
      (1.1% vs 2.0%, P = .014 and 1.2% vs 2.5%, P = .027, respectively) and
      multivariate analyses (P = .007 and P = .038, respectively). No significant
      differences in asymmetry of thickness parameters were found between glaucoma
      suspect and healthy groups (all P > .718). However, significant differences in
      asymmetry of thickness parameters between glaucoma suspects and glaucoma patients
      (P < .01) were found for all parameters. CONCLUSION: Inter-eye vessel density
      asymmetry can be quantified by OCT-A measurement. Glaucoma suspects have
      significantly greater vessel density asymmetry than healthy eyes. Longitudinal
      studies are needed to better characterize the relationship of vessel density
      asymmetry with the development and progression of glaucoma.

PMID- 29580977
TI  - Difluprednate for the Treatment of Uveitic Cystoid Macular Edema.
AB  - PURPOSE: To describe clinical outcomes associated with the use of topical
      difluprednate in treating uveitic cystoid macular edema. DESIGN: Retrospective,
      interventional case series. METHODS: Setting: Medical record review in a tertiary
      care uveitis center. PATIENT POPULATION: Fifty-eight patients (72 eyes) with
      uveitic cystoid macular edema (CME) treated with difluprednate 0.05% ophthalmic
      solution between June 2012 and May 2016. MAIN OUTCOME MEASURES: Macular central
      subfield thickness (CST) determined by optical coherence tomography, improvement
      of CME (>=20% reduction in CST or resolution), and resolution of CME (CST <= 320
      MUm with no cysts) at 30 days after starting treatment. Outcomes were assessed up
      to 90 days. RESULTS: CST on average decreased by 17% (95% CI: -33%, -7%) for eyes
      using only difluprednate (n = 43) and by 6% (95% CI: -17%, -2%) for eyes in
      patients using concomitant systemic immunosuppressive therapy (n = 29) at 30
      days, a 12% difference between groups (95% CI: 2%, 21%, P = .02). Of eyes on
      difluprednate alone, 76% had improvement and 48% had resolution of CME. In
      patients using systemic therapy, 37% of eyes had improvement and 17% had
      resolution. Eight eyes (11%) had an intraocular pressure (IOP) > 24 mm Hg within
      the first 30 days. By 90 days, CME had improved in 69% of all eyes and resolved
      in 43% of eyes, with only 9 patients starting or increasing systemic
      immunosuppressive medications and 2 patients receiving periocular corticosteroid
      injections. CONCLUSIONS: Difluprednate was associated with an improvement in
      uveitic CME and could be a reasonable first-line therapy. IOP should be closely
      monitored.

PMID- 29580978
TI  - Sheep as a model for evaluating mesenchymal stem/stromal cell (MSC)-based
      chondral defect repair.
AB  - Osteoarthritis results from the degradation of articular cartilage and is one of
      the leading global causes of pain and immobility. Cartilage has a limited
      capacity for self-repair. While repair can be enhanced through surgical
      intervention, current methods often generate inferior fibrocartilage and repair
      is transient. The development of tissue engineering strategies to improve repair
      outcomes is an active area of research. While small animal models such as rodents
      and rabbits are often used in early pre-clinical work, larger animals that better
      recapitulate the anatomy and loading of the human joint are required for late
      stage preclinical evaluation. Because of their physiological similarities to
      humans, and low cost relative to other large animals, sheep are routinely used in
      orthopedic research, including cartilage repair studies. In recent years, there
      has been considerable research investment into the development of cartilage
      repair strategies that utilize mesenchymal stem/stromal cells (MSC). In contrast
      to autologous chondrocytes derived from biopsies of articular cartilage, MSC
      offer some benefits including greater expansion capacity and elimination of the
      risk of morbidity at the cartilage biopsy site. The disadvantages of MSC are
      related to the challenges of inducing and maintaining a stable chondrocyte-like
      cell population capable of generating hyaline cartilage. Ovine MSC (oMSC) biology
      and their utility in sheep cartilage repair models have not been reviewed.
      Herein, we review the biological properties of MSC derived from sheep tissues,
      and the use of these cells to study articular cartilage repair in this large
      animal model.

PMID- 29580979
TI  - Bone morphogenetic proteins for articular cartilage regeneration.
AB  - Degeneration of articular cartilage (AC) tissue is the most common cause of
      osteoarthritis (OA) and rheumatoid arthritis. Bone morphogenetic proteins (BMPs)
      play important roles in bone and cartilage formation. This article reviews the
      experimental and clinical applications of BMPs in cartilage regeneration.
      Experimental evidence indicates that BMPs play an important role in protection
      against cartilage damage caused by inflammation or trauma, by binding to
      different receptor combinations and, consequently, activating different
      intracellular signaling pathways. Loss of function of BMP-related receptors
      contributes to the decreased intrinsic repair capacity of damaged cartilage and,
      thus, the multifunctional effects of BMPs make them attractive tools for the
      treatment of cartilage damage in patients with degenerative diseases. However,
      the development of BMP therapy as a treatment modality for cartilage regeneration
      has been hampered by certain factors, such as the eligibility of participants in
      clinical trials, financial support, drug delivery carrier safety, availabilities
      of effective scaffolds, appropriate selection of optimal dose and timing of
      administration, and side effects. Further research is needed to overcome these
      issues for future routine clinical applications. Research and development leading
      to the successful application of BMPs can initiate a new era in the treatment of
      cartilage degenerative diseases like OA.

PMID- 29580980
TI  - Tumor suppressor ZHX2 restricts hepatitis B virus replication via epigenetic and
      non-epigenetic manners.
AB  - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the stable
      genomic form as the template for viral transcription, plays a crucial role in
      viral persistence which remains a major global health problem. While accumulating
      evidence suggests the involvement of transcription factors and epigenetic
      machinery in cccDNA transcription, the roles of host transcription factors which
      contribute to epigenetic modification of cccDNA remain largely unknown. Zinc
      finger and homeoboxes 2 (ZHX2) is abundantly expressed in adult hepatocytes,
      where it acts as a transcriptional repressor and tumor suppressor by directly
      inhibiting the promoter activities of target genes. However, whether ZHX2
      influences HBV replication or is involved in cccDNA epigenetic regulation remain
      unknown. In this study, we investigated the role of ZHX2 in cccDNA transcription.
      Analysis of immunohistochemistry showed that ZHX2 nuclear expression negatively
      correlated with serum HBV DNA and HBeAg. Remarkably, ZHX2 significantly decreased
      HBV antigens expression, pregenomic RNA (pgRNA) and HBV core particle DNA
      production both in vitro and in mouse livers supporting HBV antigens expression
      and cccDNA transcription. Dual luciferase and cccDNA ChIP assays confirmed that
      ZHX2 could bind to cccDNA and transcriptionally inhibit HBV promoter activities.
      In addition, ZHX2 suppressed the expression of histone regulator genes, such as
      cccDNA bound p300/CBP, and led to epigenetic repression of cccDNA. These findings
      highlight the roles of a novel restriction factor, ZHX2, in modulating HBV
      replication via regulating HBV promoter activities and cccDNA modifications. This
      study furthers our understanding of HBV transcription from cccDNA and offers new
      insights on potential HBV therapy.

PMID- 29580981
TI  - Improved intracellular PHA determinations with novel spectrophotometric
      quantification methodologies based on Sudan black dye.
AB  - The presence of intracellular polyhydroxyalkanoates (PHAs) is usually studied
      using Sudan black dye solution (SB). In a previous work it was shown that the PHA
      could be directly quantified using the absorbance of SB fixed by PHA granules in
      wet cell samples. In the present paper, the optimum SB amount and the optimum
      conditions to be used for SB assays were determined following an experimental
      design by hybrid response surface methodology and desirability-function. In
      addition, a new methodology was developed in which it is shown that the amount of
      SB fixed by PHA granules can also be determined indirectly through the absorbance
      of the supernatant obtained from the stained cell samples. This alternative
      methodology allows a faster determination of the PHA content (involving 23 and 42
      min for indirect and direct determinations, respectively), and can be undertaken
      by means of basic laboratory equipment and reagents. The correlation between PHA
      content in wet cell samples and the spectra of the SB stained supernatant was
      determined by means of multivariate and linear regression analysis. The best
      calibration adjustment (R2 = 0.91, RSE: 1.56%), and the good PHA prediction
      obtained (RSE = 1.81%), shows that the proposed methodology constitutes a
      reasonably precise way for PHA content determination. Thus, this methodology
      could anticipate the probable results of the above mentioned direct PHA
      determination. Compared with the most used techniques described in the scientific
      literature, the combined implementation of these two methodologies seems to be
      one of the most economical and environmentally friendly, suitable for rapid
      monitoring of the intracellular PHA content.

PMID- 29580982
TI  - Real-time PCR-based method for rapid detection of Aspergillus niger and
      Aspergillus welwitschiae isolated from coffee.
AB  - Some species from Aspergillus section Nigri are morphologically very similar and
      altogether have been called A. niger aggregate. Although the species included in
      this group are morphologically very similar, they differ in their ability to
      produce mycotoxins and other metabolites and their taxonomical status has evolved
      continuously. Among them, A. niger and A. welwitschiae are ochratoxin A and
      fumonisin B2 producers and their detection and/or identification is of crucial
      importance for food safety. The aim of this study was the development of a real
      time PCR-based method for simultaneous discrimination of A. niger and A.
      welwitschiae from other species of the A. niger aggregate isolated from coffee
      beans. One primer pair and a hybridization probe specific for detection of A.
      niger and A. welwitschiae strains were designed based on the BenA gene sequences,
      and used in a Real-time PCR assay for the rapid discrimination between both these
      species from all others of the A. niger aggregate. The Real-time PCR assay was
      shown to be 100% efficient in discriminating the 73 isolates of A. niger/A.
      welwitschiae from the other A. niger aggregate species analyzed as a negative
      control. This result testifies to the use of this technique as a good tool in the
      rapid detection of these important toxigenic species.

PMID- 29580983
TI  - A comparison of ergosterol and PLFA methods for monitoring the growth of
      ligninolytic fungi during wheat straw solid state cultivation.
AB  - Ergosterol, total phospholipid fatty acid (PLFA) and linoleic acid (18:2n-6) have
      all been used to determine fungal growth. This paper compares these methods to
      assess the growth of four different saprotrophic fungal species during solid
      state cultivation using a wheat straw substrate that have not been compared or
      measured previously. Ergosterol production appeared to track the mycelia growth
      well but its production differed considerably between fungi. This means that a
      specific conversion factor needs to be determined and applied for any given
      fungus. In comparison, measurements of total PLFA and linoleic acid only showed
      promise for determining the growth of Postia placenta due to the positive
      correlation with ergosterol measurements. In contrast, the other fungi tested
      (Phanerochaete chrysosporium, Serpula lacrymans and Schizophyllum commune) showed
      either no correlation or in some cases a negative correlation using this assay.
      The novel findings highlight the variation in fungal fatty acid between species,
      culture conditions and durations of incubation; suggesting that measurement of
      linoleic acid is only usable in specific cases. These findings provide important
      consideration for the study of fungi growing in solid substrates and suggest that
      the use of PLFA might bias diversity indices.

PMID- 29580984
TI  - Monitoring cellular redox state under hypoxia using a fluorescent sensor based on
      eel fluorescent protein.
AB  - Genetically encoded fluorescent sensors are widely used to visualize secondary
      messengers, metabolites and dynamic events in living cells. However, almost all
      of these sensors are based on Aequorea GFPs or GFP-like proteins, which do not
      correctly maturate and fluoresce under hypoxia or anoxic conditions, greatly
      limiting their application in biomedical research. Herein, we provide a novel
      strategy for design of sensors and report a series of thiol redox-sensitive
      sensor based on a recently discovered oxygen-independent fluorescent protein UnaG
      from Japanese eel. These redox sensors have large dynamic range, rapid
      responsiveness, a flexible "switch", and pH-independence, are particularly
      compatible with hypoxia conditions, and therefore represent a substantial
      improvement for live-cell redox measurement. We further demonstrated the
      versatility of these redox sensors, by simultaneously monitoring redox changes
      and hypoxia state in living cells, thereby proving its capability as a powerful
      and flexible tool for indexing multidimensional metabolism data in the context of
      physiological stressors and pathological states. These redox sensors are not only
      the first case of UnaG-based functional sensors, but also the first case of
      functional sensors based on non GFP-like proteins. Based on this strategy, more
      oxygen-independent biosensors could be developed, hence, provide new
      opportunities for bioimaging.

PMID- 29580985
TI  - Tributyltin role on the serotonin and histamine receptors in human umbilical
      artery.
AB  - Some studies in animals suggest that TBT may constitute a risk factor for
      cardiovascular diseases. Hence, the main purpose of this study was to investigate
      in human umbilical artery (HUA) the effect of TBT on vascular reactivity, manly
      in serotonin (5-HT) and histamine receptors. Using standard organ bath
      techniques, rings of HUA without endothelium were contracted by 5-HT and
      histamine. We also investigated the effect of TBT on the expression of the
      receptors using Real-time PCR. The results show that TBT short term effects
      include concentration-dependent relaxation. Moreover, at long term exposures, the
      arteries treated with 100 MUM of TBT do not have contraction capacity when 5-HT
      is added, and the gene expression of 5-HT2A receptor decrease. Regarding
      histamine, it was demonstrated that TBT induces a concentration-dependent
      relaxation and the H1 gene expression levels decrease. In conclusion TBT modifies
      the activity and expression of 5-HT and histamine receptors.

PMID- 29580986
TI  - Maduramicin induces apoptosis in chicken myocardial cells via intrinsic and
      extrinsic pathways.
AB  - Maduramicin is one of the most extensively used anticoccidial drugs for the
      treatment of Eimeria spp. infections. However, overdosage, misuse and drug
      interactions have resulted in the development of ionophore toxic syndrome. Heart
      and skeletal muscles have been identified as the main target organs of toxicity.
      In the present study, primary chicken myocardial cells were isolated to
      investigate the toxicity and underlying mechanisms of maduramicin. Our results
      showed that maduramicin causes morphological changes and a decrease in the
      viability of chicken myocardial cells. Annexin V-FITC/PI and 4',6-diamidino-2
      phenylindole (DAPI) staining showed a significant increase in the number of
      apoptotic cells. Furthermore, caspases-3/8/9 were activated at the gene and
      protein levels and this was accompanied by the upregulation of apoptosis-related
      genes, including bcl-2, bax, and cytochrome C. Treatment with the pan-caspase
      inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (O-Me) fluoromethyl ketone (z-VAD-fmk)
      ameliorated the apoptosis and cytotoxicity. Furthermore, intracellular Ca2+ and
      reactive oxygen species (ROS) were elevated, whereas mitochondrial membrane
      potential (MMP) and intracellular glutathione (GSH) decreased with exposure to
      maduramicin. The antioxidant N-acetyl-cysteine (NAC) had no significant effect on
      maduramicin-induced cytotoxicity and apoptosis. Taken together, our findings
      demonstrate that maduramicin is cytotoxic to primary chicken myocardial cells via
      caspase dependent and independent apoptotic pathways.

PMID- 29580987
TI  - Interaction of carbon monoxide-releasing ruthenium carbonyl CORM-3 with plasma
      fibronectin.
AB  - Inhaled carbon monoxide (CO) gas is highly toxic, but the human body produces low
      levels of CO for vasoregulation and other purposes. Given the established
      protective roles of low concentrations of CO gas against a panel of pathological
      insults, CO-releasing molecules (CORMs) have been developed and examined in
      disease models both in vitro and in vivo. Among CORMs, CORM-3
      [Ru(CO)3Cl(glycinate)], a ruthenium carbonyl compound, has been extensively
      studied since it is water-soluble and is suitable for in vivo application. As one
      of the most prominent features of CO gas is its anti-fibrotic effect, we examined
      the effects of CORM-3 on mouse embryonic fibroblasts (MEFs). The application of 1
      mM CORM-3 to MEFs resulted in the decreased syntheses of collagens I and III
      within 24 h, confirming an anti-fibrotic effect. To our surprise, CORM-3 caused a
      rapid (within 1 h) dissociation of cell-associated plasma fibronectin (FN) from
      the cells, which is associated with formation of a reduction-resistant oligomer
      of plasma FN. This aberrant oligomerization of plasma FN was reproduced using
      purified FN in vitro. Furthermore, we showed that RuCl3, but not another water
      soluble CORM, CORM-A1 [Na2H3BCO2], also oligomerized plasma FN in vitro. FN
      depletion from the serum substantially ameliorates cell death by prolonged (72 h)
      exposure to CORM-3, suggesting a detrimental role of FN oligomerization on cell
      death. Taken together, we reveal for the first time that FN is a CORM-3
      interactive plasma protein, and that the CORM-3-FN interaction is involved in the
      death of fibroblasts.

PMID- 29580988
TI  - Kruppel-like factor 4 regulates keratinocyte senescence.
AB  - Keratinocyte replicative senescence has an important role in time-related changes
      of epidermis. Previous studies demonstrated that miRNAs play key roles in
      inhibiting proliferation and in the acquisition of the keratinocyte senescent
      phenotype as well as in individual ageing. Kruppel-like factor 4 is a
      transcription factor with dual functions in keratinocytes, being a stemness
      factor and a pro-differentiation factor. Interestingly, in skin squamous cell
      carcinomas KLF4 expression is strongly down-regulated or absent. While KLF4
      involvement in senescence and ageing has not been investigated yet. Here, we show
      that Klf4 protein decreases during keratinocyte replicative senescence and during
      physiological skin aging, while its mRNA level does not change. We demonstrated
      that the senescence-associated miR-34a regulates post-transcriptionally Klf4
      expression. KLF4 silencing is sufficient to induce a senescent phenotype in
      primary keratinocytes and ectopic miR-34a over-expression phenocopies this
      result. Our findings identify a novel regulatory loop between miR-34a and KLF4
      during keratinocytes replicative senescence. This regulatory loop, beside aging,
      may play a role in age-related pathologies.

PMID- 29580989
TI  - AMP-activated protein kinase stabilizes FOXO3 in primary myotubes.
AB  - AMP-activated protein kinase (AMPK) is a critical enzyme in conditions of
      cellular energy deficit such as exercise, hypoxia or nutritional stress. AMPK is
      well known to regulate protein degradation pathways notably through FOXO-related
      axis. In this study, we investigated the implication of AMPK activation in FOXO3
      expression and stability in skeletal muscle primary myotubes. First, time course
      and dose response studies revealed optimal AICAR treatment duration and dose in
      skeletal muscle cells. Then, experiments with cycloheximide treatment of primary
      myotubes highlighted that AICAR infusion extends FOXO3 protein half-life. Our
      results also showed that AICAR treatment or nutrient depletion increases FOXO3
      expression in primary myotubes and the expression of the mitochondrial E3 ligase
      Mul1 involved in mitochondrial turnover (mitophagy). In AMPK KO cells, nutrient
      depletion failed to alter the level of some FOXO3-dependent atrophic genes,
      including LC3B, BNIP3, and the mitochondrial E3 ligase Mul1, but not the
      expression of other genes (i.e. FOXO1, Gabarapl1, MAFbx, MuRF1). In summary, our
      data highlight that AMPK stabilizes FOXO3 and suggest a role in the first
      initiation step of mitochondrial segregation in muscle cells.

PMID- 29580990
TI  - Copper induces structural changes in N-terminus of human prion protein.
AB  - Copper ions reportedly bind to the cellular prion (PrPC) and induce PrP
      proteinase K (PK) resistant from (PrPres). PrPC also plays a role in response to
      oxidative stress. By using purified human PrP23-98 containing octarepeats, we
      have found that Cu(II) induces PrPres determined by Western blots and atomic
      force microscopy, and structural changes detected by hydrogen/deuterium exchange
      in the PrP N-terminus. Therefore, we have provided the evidence that copper ions
      play an important role in the change of N-terminus of human prion protein.

PMID- 29580991
TI  - Ferritin heavy chain controls the HIF-driven hypoxic response by activating the
      asparaginyl hydroxylase FIH.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a key player in cellular response to
      hypoxia. The stability and transcriptional activity of this protein are oxygen
      dependently regulated by the prolyl hydroxylases PHD1-3 and the asparaginyl
      hydroxylase FIH. Recently, ferritin heavy chain (FTH1) has been characterized to
      reinforce the HIF-1 signaling pathway in an indirect way through the inhibition
      of PHD activity by depleting the free iron pool in the cytoplasm. In the present
      study, we addressed the role of FTH1 in the FIH control of HIF-1 activity.
      Unexpectedly, immunoprecipitation analyses revealed that FTH1 directly interacted
      with FIH. In an in vitro hydroxylation assay, FTH1 was found to facilitate the
      FIH-mediated Asn803 hydroxylation in HIF-1alpha. As expected, FTH1 prevented the
      recruitment of p300 to HIF-1alpha through the Asn803 hydroxylation. In luciferase
      reporter analyses, FTH1 was found to repress the transcriptional activity of HIF
      1alpha in HCT116 cells under either normoxic or hypoxic conditions. Consequently,
      FTH1 downregulated the expression of the HIF-1 target genes, such as VEGF, CA9
      and GLUT1. Our results suggest a new role of FTH1 as a co-regulator for the FIH
      mediated oxygen sensing pathway. Since HIF-1alpha is involved in pathogenesis of
      diverse hypoxia-associated diseases, we propose that FTH1 be a potential target
      in developing new therapeutic strategies against such diseases.

PMID- 29580992
TI  - Comparative toxicity and contrast enhancing assessments of Gd2O3@BSA and MnO2@BSA
      nanoparticles for MR imaging of brain glioma.
AB  - The albumin-templated Gd2O3 and MnO2 nanoparticles (NPs) have been developed as a
      new type of magnetic resonance (MR) T1 contrast agents. However, their potential
      toxicity and applicability for MR imaging of brain gliomas has not been fully
      explored so far. In this study, we prepared Gd2O3@BSA and MnO2@BSA nanoparticles
      (NPs) and investigated their toxicity comprehensively and comparatively by H&E
      staining, blood biochemical analysis, and adverse outcome pathways testing. It is
      revealed that both Gd2O3@BSA and MnO2@BSA NPs are biocompatible at a rational
      dose level. Although the relaxivity of MnO2@BSA NPs is less than that of
      Gd2O3@BSA NPs, the MnO2@BSA NPs lead to a greater contrast enhancement in the
      brain glioma due to the controlled release of Mn ions under the acidic tumor
      microenvironmental conditions. These comparative toxicity and contrast
      enhancement data are of fundamental importance for the clinical translation of
      Gd2O3@BSA and MnO2@BSA NPs as MR contrast agents for brain glioma diagnosis.

PMID- 29580993
TI  - Genome-wide identification of circRNAs involved in tomato fruit coloration.
AB  - Circular RNAs (circRNAs) are an emerging class of non-coding RNAs in plants. Our
      aim is to identify the circRNAs with different expression levels between tomato
      fruits from two cultivars ('Jinling Fenyu' and 'Jinling Moyu') at two different
      developmental stages. Following high-throughput sequencing, 3796 circRNAs were
      identified, and 243 circRNAs were shared in the four samples. As compared with
      the fruit at mature green stage, the expression levels of 273 and 89 circRNAs
      were significantly altered in the fruit at turning stage from 'Jinling Fenyu' and
      'Jinling Moyu', respectively. Moreover, the parental genes of the circRNAs with
      significantly different expression level were mainly involved in metabolic,
      cellular and single-organism process and played roles in catalytic activity and
      binding based on GO (Gene Ontology) analysis. The results suggested that circRNAs
      were widespread in tomato and were generated from different chromosomes and
      diverse genomic regions. Some circRNAs were specific in tomato fruits at
      different developmental stages, which enriches the number of circRNAs in plants
      involved in fruit coloration and ripening. This study provides the first genome
      wide profile of circRNAs involved in tomato fruit coloration and lays a
      foundation for studying the potential biological functions of circRNAs involved
      in fruit ripening.

PMID- 29580994
TI  - Modification of gum ghatti via grafting with acrylamide and analysis of its
      flocculation, adsorption, and biodegradation properties.
AB  - In this work, an environmentally friendly gum ghatti-crosslinked-polyacrylamide
      (Gg-cl-PAAM) hydrogel was synthesized from gum ghatti (Gg) and acrylamide (AAM)
      using a microwave-assisted grafting technique, and tested for use in water
      purification applications as an adsorbent and flocculent. The Gg-cl-PAAM was
      characterized using SEM, FTIR, and TGA, and displayed pH responsive swelling
      behavior, with maximum swelling (2117%) observed in solution with neutral pH. The
      flocculation characteristics of Gg-cl-PAAM were tested in clay solutions as a
      function of pH, temperature, and the polymer mass loading, showing that the best
      performance is obtained at neutral pH at 40 degrees C. The adsorption capacities
      of Gg-cl-PAAM for the removal different dyes such as brilliant green (BG),
      rhodamine B (RhB), congo red (CR), and methyl orange (MO) were tested, revealing
      that the adsorption of all dyes followed the Langmuir isotherm model, with qm
      values of 523.62mgg-1 for BG, 421.60mgg-1 for RhB, 179.09mgg-1 for CR, and
      173.69mgg-1 for MO. Finally, the environmentally friendly nature of Gg-cl-PAAM
      was examined using the soil-burial composting method, which demonstrated 93%
      degradation of the Gg-cl-PAAM hydrogel within 60days.

PMID- 29580995
TI  - Modifying cellulose with metaphosphoric acid and its efficiency in removing
      brilliant green dye.
AB  - In this study, cellulose was chemically modified through the addition of the
      phosphorylating agent, metaphosphoric acid in order to obtain a new material
      (MPCel) with higher adsorptive properties than the starting material. Both
      materials were characterized by infrared spectroscopy, X-ray diffraction, solid
      state phosphorus-31 nuclear magnetic resonance spectroscopy and thermogravimetric
      analysis. Maximal adsorption capacity, at 45 degrees C for pure cellulose, was
      90.5mgg-1, at pH=10 and contact time of 40min, with experimental isotherms better
      adjusted to the Langmuir model. MPCel at the same temperature conditions showed
      contact time of 10min, pH=10, and maximal adsorption capacity of 150.0mgg-1,
      being better adjusted to the Temkin model. The kinetic study of both materials
      followed the pseudo-second-order model. Modification successfully occurred and
      both adsorbents were shown able to be capable of removing the brilliant green
      dye, but MPCel was more efficient for purpose, when compared to the pure
      cellulose.

PMID- 29580996
TI  - Preparation of starch nanoparticles loaded with quercetin using nanoprecipitation
      technique.
AB  - Nanoparticles of starches from different botanical origin were prepared by
      nanoprecipitation using 0.1M hydrochloric acid as non-solvent. The morphology and
      the particle size were analyzed using field emission scanning electron microscopy
      and dynamic light scattering. The nanoparticles were spherical and their sizes
      vary depending on the origin and the concentration of the starch solution. Starch
      nanoparticles loaded with quercetin were prepared. In-vitro release studies of
      the quercetin from the starch nanoparticles were performed in 35% ethanol as a
      release medium. The starch origin affects the quercetin loading percentage, the
      release kinetics and the antioxidant activity of the produced nanoparticles. The
      starch-quercetin nanoparticles from cereal origin showed the lowest loading
      percentage and the lowest fraction released of quercetin in comparison with
      nanoparticles from tuber and legume origin. The release kinetics seem to be
      controlled mainly by Fickian diffusion which have been revealed fitting the
      release data to the Peppas-Sahlin model.

PMID- 29580997
TI  - Modification of chitin with high adsorption capacity for methylene blue removal.
AB  - Porous chitin sorbents (PChs) with different content of chitin, ranging from 0.9%
      to 3.5%, were prepared by gel method with CaBr2.xH2O/CH3OH solution and
      characterized by FT-IR, XRD and SEM. The adsorption isotherms and kinetic
      analysis of methylene blue (MB) onto PChs were studied. Experimental results
      illustrated lower crystallinity and more pores of PChs containing 3.5% chitin
      displayed higher adsorption capacity, the removal of MB was 79.8%. The adsorption
      equilibrium isotherm curve of MB onto PChs adsorbents conformed to the Freundlich
      equation. The PFO, PSO and Weber-Morris models were applied to fit with the
      adsorption kinetics. The results demonstrated the adsorption of MB might be the
      mass transfer of heterogeneous system and involve multiple diffusion steps. The
      adsorption capacity of PChs with 3.5% chitin can maintain 65% removal ratio of MB
      after being used six adsorption-desorption cycles. It was supposed that PChs may
      be a promising, cheap, environmentally friendly and efficient adsorbent for some
      dye wastewater treatment in the near future.

PMID- 29580998
TI  - A halotolerant bifunctional beta-xylosidase/alpha-l-arabinofuranosidase from
      Colletotrichum graminicola: Purification and biochemical characterization.
AB  - A beta-xylosidase from Colletotrichum graminicola (Bxcg) was purified. The enzyme
      showed high halotolerance, retaining about 63% of the control activity in the
      presence of 2.5molL-1 NaCl. The presence of NaCl has not affected the optimum
      reaction temperature (65 degrees C), but the optimum pH was slightly altered
      (from 4.5 to 5.0) at high salt concentrations. Bxcg was fully stable at 50
      degrees C for 24h and over a wide pH range even in the presence of NaCl. In the
      absence of salt Bxcg hydrolyzed p-nitrophenyl-beta-d-xylopyranoside with maximum
      velocity of 348.8+/-11.5Umg-1 and high catalytic efficiency (1432.7+/-47.3Lmmol
      1s-1). Bxcg revealed to be a bifunctional enzyme with both beta-xylosidase and
      alpha-l-arabinofuranosidase activities, and hydrolyzed xylooligosaccharides
      containing up to six pentose residues. The enzyme showed high synergistic effect
      (3.1-fold) with an endo-xylanase for the hydrolysis of beechwood xylan, either in
      the absence or presence of 0.5molL-1 NaCl, and was tolerant to different organic
      solvents and surfactants. This is the first report of a halotolerant bifunctional
      beta-xylosidase/alpha-l-arabinofuranosidase from C. graminicola, and the enzyme
      showed attractive properties for application in lignocellulose hydrolysis,
      particularly under high salinity and/or in the presence of residues of
      pretreatment steps.

PMID- 29580999
TI  - Highly stable single-strand-specific 3'-nuclease/nucleotidase from Legionella
      pneumophila.
AB  - The Gram-negative bacterium Legionella pneumophila is one of the known
      opportunistic human pathogens with a gene coding for a zinc-dependent S1-P1 type
      nuclease. Bacterial zinc-dependent 3'-nucleases/nucleotidases are little
      characterized and not fully understood, including L. pneumophila nuclease 1
      (Lpn1), in contrast to many eukaryotic representatives with in-depth studies
      available. To help explain the principle properties and role of these enzymes in
      intracellular prokaryotic pathogens we have designed and optimized a heterologous
      expression protocol utilizing E. coli together with an efficient purification
      procedure, and performed detailed characterization of the enzyme. Replacement of
      Ni2+ ions by Zn2+ ions in affinity purification proved to be a crucial step in
      the production of pure and stable protein. The production protocol provides
      protein with high yield, purity, stability, and solubility for structure-function
      studies. We show that highly thermostable Lpn1 is active mainly towards RNA and
      ssDNA, with pH optima 7.0 and 6.0, respectively, with low activity towards dsDNA;
      the enzyme features pronounced substrate inhibition. Bioinformatic and
      experimental analysis, together with computer modeling and electrostatics
      calculations point to an unusually high positive charge on the enzyme surface
      under optimal conditions for catalysis. The results help explain the catalytic
      properties of Lpn1 and its substrate inhibition.

PMID- 29581000
TI  - Preparation and characterization of contact active antibacterial surface based on
      chemically modified nanofibrillated cellulose by phenanthridinium silane salt.
AB  - The main object of this research is chemical modification of the nanofibrillated
      cellulose (NFC) surface with a phenanthridinium silane salt to develop durable
      non-leaching antibacterial surface. Initially, (3-trimethoxysilylpropyl)
      phenanthridinium iodide (TMSPhI) as an antibacterial agent was synthesized using
      (3-chloropropyl trimethoxysilane) (CPTMS) and phenanthridine in the presence of
      potassium iodide. Subsequently, NFC was cationized by reaction of its hydroxyl
      groups with the trimethoxysilane group of TMSPhI to prepare the modified sample
      (NFC-TMSPhI). The synthesized TMSPhI was characterized by FT-IR, 1H and 13C NMR
      spectroscopies. The modified NFC samples were also characterized by FE-SEM/EDX,
      XRD, TGA, elemental analysis, contact angle measurement, FT-IR, UV-Visible and
      fluorescence spectroscopies. The obtained NFC-TMSPhI samples presented
      fluorescence property at the maximum emission wavelength in the range of 539-549
      nm. Additionally, the antibacterial activity of the modified samples were
      evaluated quantitatively against Gram-positive (S. aureus) and Gram-negative (E.
      coli) bacteria. All the modified samples displayed promising results with at
      least bacteriostatic effect or bactericidal properties. Finally, the cytotoxic
      effect of the modified sample on human dermal fibroblasts (HDFs) and two cancer
      cell lines (MCF-7 and Hela) was investigated that showed dose- and surface charge
      dependent toxicity.

PMID- 29581001
TI  - Supramolecular hydrogel formation between chitosan and hydroxypropyl beta
      cyclodextrin via Diels-Alder reaction and its drug delivery.
AB  - Chitosan-cyclodextrin hydrogel (CFCD) was prepared via Diels-Alder reaction
      between furfural functionalized chitosan (CF) and N-maleoyl alanine
      functionalized hydroxypropyl beta-cyclodextrin (HPCD-AMI) in aqueous media
      without any catalyst or initiator. The CF and HPCD-AMI were confirmed by Fourier
      transform infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy.
      The resultant CFCD hydrogel was characterized in terms of thermal peripteries,
      microstructure, rheology behavior, and swelling capacity. The rheology analysis
      found that the storage modulus G' ranged from 1pa to 1200pa as the degree of
      furfural substitute on chitosan increased from 2.6% to 28.3%, indicating the
      hydrogel strength can be tuned readily by reaction stoichiometry. The swelling
      behaviors proved that CFCD hydrogel was pH-responsive with low swelling capacity,
      which would be preferable for drug delivery. Drug adsorption analysis showed the
      introduction of cyclodextrin into CFCD hydrogels promoted drug adsorption
      capacity. In addition, methyl orange cumulative release in PBS buffer was only
      48.85% after 24h, suggesting CFCD hydrogel had good sustained release capacity on
      the loaded drug.

PMID- 29581002
TI  - Design, characterization and preliminary biological evaluation of new lignin-PLA
      biocomposites.
AB  - The study focuses on the obtainment of new poly (lactic acid)-lignin
      biocomposites. The effect of lignin loading on the morphology and mechanical
      properties, as well as the water uptake behaviour of the obtained biocomposites,
      was investigated in order to elucidate the influence of lignin incorporation into
      a poly (lactic acid) matrix. The addition of 7% lignin improved the Young modulus
      and led to a decrease in the tensile strength in comparison with the
      corresponding values of the poly (lactic acid) matrix, while the water sorption
      capacity slowly decreased. A subsequent increment in lignin loading from 7 to
      15wt% resulted in an increase in tensile strength, as well as in a decline in the
      water sorption capacity. These results show the importance of the lignin content
      in controlling the properties of such composites. Furthermore, the behaviour of
      the PLA-lignin biocomposites in SBF was another concern for evaluation of
      mechanical performance and biological activity. The mechanical performance
      declined after immersion in simulated body fluid, but the properties of the
      biomaterials remained sufficiently high for the perspective of their use in
      medical applications. In-vitro biocompatibility studies evidenced that the
      addition of lignin to a poly (lactic acid) matrix can allow tailoring the final
      properties of the composites without inducing any significant change in cell
      metabolic activity (compared to poly (lactic acid) itself).

PMID- 29581003
TI  - Carbazole ligands as c-myc G-quadruplex binders.
AB  - The interactions of c-myc G-quadruplex with three carbazole derivatives were
      investigated by UV-Vis spectrophotometry, fluorescence, CD spectroscopy, and
      molecular modeling. The results showed that a combination of carbazole scaffold
      functionalized with ethyl, triazole and imidazole groups resulted in
      stabilization of the intramolecular G-quadruplex formed by the DNA sequence
      derived from the NHE III1 region of c-myc oncogene (Pu22). Binding to the G
      quadruplex Pu22 resulted in the significant increase in fluorescence intensity of
      complexed ligands 1-3. All ligands were capable of interacting with G4 DNA with
      binding stoichiometry indicating that two ligand molecules bind to G-quadruplex
      with comparable affinity, which agrees with binding model of end-stacking on
      terminal G-tetrads.

PMID- 29581004
TI  - Preparation of biocompatible and biodegradable silk fibroin/chitin/silver
      nanoparticles 3D scaffolds as a bandage for antimicrobial wound dressing.
AB  - One of the most serious challenge in wound care is difficulty of the infection
      control in wound healing process. Wound dressings with antimicrobial effects are
      useful to minimize the bacterial infections of wounds. In this study a
      biocompatible and biodegradable silk fibroin/chitin nanocomposite scaffolds with
      various content of silver nanoparticles (0.001, 0.01, and 0.1%) were fabricated
      via freeze-drying method for successful wound dressing application. The
      nanocomposite scaffolds have biocompatibility with high antimicrobial effects,
      good mechanical properties, and high porosity. Furthermore, swelling and water
      uptake, blood clotting, and biodegradability were also investigated. The
      antimicrobial evaluation with both disc diffusion method and colony counts imply
      that nanocomposite scaffolds have high antimicrobial activity and could
      successfully inhibit the growth of E. coli, S. aureus, and C. albicans. Also
      proliferation, cell viability, and cell attachment with MTT assay and DAPI
      staining on nHFFF2 cell, have proved the cytocompatibility nature of the
      nanocomposite scaffolds. All results revealed that prepared nanocomposite
      scaffolds are good candidate for wound dressing and could be use in further in
      vivo uses.

PMID- 29581005
TI  - Influence of polysiloxane as nanofiller on the surface, optical and thermal
      properties of guar gum grafted polyaniline matrix.
AB  - Mesoporous silica containing nanocomposites of in situ polymerised aniline
      grafted on guar gum (GG), were synthesised by sol-gel technique. Characterization
      of samples with respect to SEM, TEM, XRD, XPS, FTIR, BET, UV-vis, and PL
      illustrated the optically active materials with diverse morphologies. Microscopic
      analysis rendered transitional changes from smooth GG to coated PANI grafts and
      dense clusters of polysiloxane nanocomposites. FTIR analysis confirmed the
      interaction of GG-PANI-Si components. XRD diffractograms illustrate tremendous
      reduction of dominant amorphous phase of GG by grafted HCl doped PANI depicted by
      characteristic peaks (centred at 2theta=~25 degrees  and 2theta=~20.0 degrees )
      in the partially crystalline and amorphous GG-g-PANI and GG-g-PANI-Si1
      nanocomposites. Phase modification through PANI grafting showed specific surface
      area of GG-g-PANI (7.6m2/g) improving immensely with low polysiloxane contents to
      ~170.6m2/g in GG-g-PANI-Si1 compared to 25.6m2/g of GG-g-PANI-Si2. The
      nanocomposites were thermally stable up to ~240 degrees C, each leaving 69% (GG-g
      PANI-Si1) and ~77% (GG-g-PANI-Si2) of inorganic residues. Both showed no thermal
      dedoping, suggesting the good thermal protection offered by polysiloxane layer.

PMID- 29581006
TI  - Amino functionalization of carboxymethyl cellulose for efficient immobilization
      of urease.
AB  - Jack bean urease (EC.3.5.1.5) was effectively immobilized onto amino
      functionalized epichlorohydrin cross-linked carboxymethyl cellulose (ECH-CMC)
      beads that were fabricated by graft co-polymerization of polyacrylamide (PAm)
      onto ECH-CMC beads in presence of potassium persulfate (KPS)/thiourea (TU)
      combined redox initiator followed by Hoffmann degradation. The progress of the
      synthesis along with immobilization processes was investigated by FTIR spectra.
      Also, the morphological structures of the beads before and after urease
      immobilizations were examined using SEM. Immobilization efficiency and
      immobilized urease amounts were estimated as a function of the amino
      functionalization degrees. The effects of pH and temperature on urease activity
      were studied. The results showed that after immobilization the optimum pH and
      temperature displayed higher shifts to 8 and 45 degrees C, respectively, which
      reveal a higher structural stability upon immobilization performance. Moreover,
      the kinetic studies indicated that the urea hydrolysis reaction, which catalyzed
      by urease enzyme displayed a good fit with Michaelis-Menten equation, and the
      kinetic parameters Km and vm were estimated to be 14+/-0.7mM and 2+/
      0.2MUmolNH3/min.mg immobilized urease, respectively. Furthermore, the immobilized
      urease maintained approximately 88% of its initial activity after the 10th reuse
      cycle.

PMID- 29581008
TI  - Editorial on special issue: Machine learning on MCI.

PMID- 29581007
TI  - Positive autoregulation of the flhDC operon in Proteus mirabilis.
AB  - Using a variety of techniques, we demonstrate the Class I regulator of the
      flagellar cascade, FlhD4C2, can activate its own expression in Proteus mirabilis.
      This activation was direct, as the FlhD4C2 protein specifically bound to its
      promoter region. The expression of bacterial genes under a positive feedback
      control can exhibit varying levels between cells due to stochastic fluctuations
      that activate the feedback loop and result in some cells in an "ON" state. Cells
      containing a chromosomal flhDC::gfp transcriptional fusion exhibited a
      heterogeneous pattern of expression within the population during growth on agar
      surfaces and the percentage of cells expressing GFP increased as cells approached
      swarmer cell differentiation. Disrupting the FlhD4C2 -mediated positive feedback
      loop significantly reduced the frequency of cells exhibiting GFP expression.

PMID- 29581009
TI  - The Virtual Shop: A new immersive virtual reality environment and scenario for
      the assessment of everyday memory.
AB  - BACKGROUND: Assessing and predicting memory performance in everyday life is a
      common assignment for neuropsychologists. However, most traditional
      neuropsychological tasks are not conceived to capture everyday memory
      performance. NEW METHOD: The Virtual Shop is a fully immersive task developed to
      assess memory in a more ecological way than traditional neuropsychological
      assessments. Two studies were undertaken to assess the feasibility of the Virtual
      Shop and to appraise its ecological and construct validity. In study 1, 20
      younger and 19 older adults completed the Virtual Shop task to evaluate its level
      of difficulty and the way the participants interacted with the VR material. The
      construct validity was examined with the contrasted-group method, by comparing
      the performance of younger and older adults. In study 2, 35 individuals with
      subjective cognitive decline completed the Virtual Shop task. Performance was
      correlated with an existing questionnaire evaluating everyday memory in order to
      appraise its ecological validity. To add further support to its construct
      validity, performance was correlated with traditional episodic memory and
      executive tasks. RESULTS: All participants successfully completed the Virtual
      Shop. The task had an appropriate level of difficulty that helped differentiate
      younger and older adults, supporting the feasibility and construct validity of
      the task. COMPARISON WITH EXISTING METHOD(S): The performance on the Virtual Shop
      was significantly and moderately correlated with the performance on the
      questionnaire and on the traditional memory and executive tasks. CONCLUSIONS:
      Results support the feasibility and both the ecological and construct validity of
      the Virtual Shop.

PMID- 29581010
TI  - Molecular cloning, expression, and characterization of UDP N-acetyl-alpha-d
      galactosamine: Polypeptide N-acetylgalactosaminyltransferase 4 from
      Cryptosporidium parvum.
AB  - Cryptosporidium spp. are the causative agents of diarrheal disease worldwide, but
      effective treatments are lacking. Cryptosporidium employs mucin-like
      glycoproteins with O-glycans to attach to and infect host intestinal epithelial
      cells. The Tn antigen (GalNAcalpha1-Ser/Thr) is an O-glycan essential for these
      processes, as Tn-specific lectins and a Tn-specific monoclonal antibody block
      attachment to and infection of host cells in vitro. The enzymes in
      Cryptosporidium catalyzing their synthesis, however, have not been studied.
      Previously, we identified four genes encoding putative UDP N-acetyl-alpha-d
      galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) in the
      genomes of three Cryptosporidium spp. Here we report the in silico analysis,
      cloning, expression, purification, and characterization of one of the four
      enzymes Cryptosporidium parvum (Cp)-ppGalNAc-T4. This enzyme contains the
      characteristic domains and motifs conserved in ppGalNAc-Ts and is expressed at
      multiple time points during in vitro infection. Recombinant soluble Cp-ppGalNAc
      T4 was enzymatically active against an unmodified EA2 peptide suggesting that it
      may function as an "initiating" ppGalNAc-T. Cp-ppGalNAc-T4 also exhibited a
      strong preference for UDP-GalNAc over other nucleotide sugar donors and was
      active against unmodified and O-glycosylated versions of the C. parvum gp40
      derived peptide, with a preference for the former, suggesting it may play a role
      in modifying this glycoprotein in vivo. Given the importance of mucin-type O
      glycosylation in Cryptosporidium spp., the enzymes that catalyze their synthesis
      may serve as potential therapeutic targets.

PMID- 29581011
TI  - A plant-like mitochondrial carrier family protein facilitates mitochondrial
      transport of di- and tricarboxylates in Trypanosoma brucei.
AB  - The procyclic form of the human parasite Trypanosoma brucei harbors one single,
      large mitochondrion containing all tricarboxylic acid (TCA) cycle enzymes and
      respiratory chain complexes present also in higher eukaryotes. Metabolite
      exchange among subcellular compartments such as the cytoplasm, the mitochondrion,
      and the peroxisomes is crucial for redox homeostasis and for metabolic pathways
      whose enzymes are dispersed among different organelles. In higher eukaryotes,
      mitochondrial carrier family (MCF) proteins transport TCA-cycle intermediates
      across the inner mitochondrial membrane. Previously, we identified several MCF
      members that are essential for T. brucei survival. Among these, only one MCF
      protein, TbMCP12, potentially could transport dicarboxylates and tricarboxylates.
      Here, we conducted phylogenetic and sequence analyses and functionally
      characterised TbMCP12 in vivo. Our results suggested that similarly to its
      homologues in plants, TbMCP12 transports both dicarboxylates and tricarboxylates
      across the mitochondrial inner membrane. Deleting this carrier in T. brucei was
      not lethal, while its overexpression was deleterious. Our results suggest that
      the intracellular abundance of TbMCP12 is an important regulatory element for the
      NADPH balance and mitochondrial ATP-production.

PMID- 29581012
TI  - The pseudo-dimeric tyrosyl-tRNA synthetase of T. brucei aminoacylates cytosolic
      and mitochondrial tRNATyr and requires both monomeric units for activity.
AB  - Aminoacyl-tRNA synthetases are essential for protein synthesis. The single-copy
      tyrosyl-tRNA synthetase (Tb-TyrRS) of T. brucei has an unusual structure and
      forms a pseudo-dimer. It is therefore twice the size than tyrosyl-tRNA
      synthetases of most other organisms. Here we show by inducible RNAi that Tb-TyrRS
      is essential for normal growth of procyclic T. brucei. Furthermore we demonstrate
      that Tb-TyrRS aminoacylates cytosolic as well as mitochondrial tRNATyr indicating
      that it is dually localized. Finally we show that individual deletion of the 36 N
      or C-terminal amino acids abolishes the function of Tb-TyrRS. This indicates
      that both monomeric units of the enzyme, the C-terminal one of which is predicted
      to lack enzymatic activity, are essential for Tb-TyrRS function. In summary our
      results together with previous studies support the notion that Tb-TyrRS might be
      a suitable drug target.

PMID- 29581013
TI  - Industry Financial Relationships in Neurosurgery in 2015: Analysis of the
      Sunshine Act Open Payments Database.
AB  - OBJECTIVE: The 2013 Physician Payments Sunshine Act mandates that all U.S. drug
      and device manufacturers disclose payments to physicians. All payments are made
      available annually in the Open Payments Database (OPD). Our aim was to determine
      prevalence, magnitude, and nature of these payments to physicians performing
      neurologic surgery in 2015 and to discuss the role that financial conflicts of
      interest play in neurosurgery. METHODS: All records of industry financial
      relationships with physicians identified by the neurological surgery taxonomy
      code in 2015 were accessed via the OPD. Data were analyzed in terms of type and
      amounts of payments, companies making payments, and comparison with previous
      studies. RESULTS: In 2015, 83,690 payments (totaling $99,048,607) were made to
      7613 physicians by 330 companies. Of these, 0.01% were >$1 million, and 73.2%
      were <$100. The mean payment ($13,010) was substantially greater than the median
      ($114). Royalties and licensing accounted for the largest monetary value of
      payments (74.2%) but only 1.7% of the total number. Food and beverage payments
      were the most commonly reported transaction (75%) but accounted for only 2.5% of
      total reported monetary value. Neurologic surgery had the second highest average
      total payment per physician of any specialty. CONCLUSIONS: The neurological
      surgery specialty receives substantial annual payments from industry in the
      United States. The overall value is driven by a small number of payments of high
      monetary value. The OPD provides a unique opportunity for increased transparency
      in industry-physician relationships facilitating disclosure of financial
      conflicts of interest.

PMID- 29581014
TI  - Magnetic Resonance Neurography in Chronic Lumbosacral and Pelvic Pain: Diagnostic
      and Management Impact-Institutional Audit.
AB  - BACKGROUND/OBJECTIVE: Low back and pelvic pain are among the most prevalent
      conditions worldwide, with major social and economic costs. The aim of this study
      was to evaluate the role of magnetic resonance neurography (MRN) of lumbosacral
      plexus in the management and outcomes of these patients with chronic pain.
      METHODS: Consecutive patients with chronic lumbosacral and pelvic pain referred
      for MRN over a year were included. Preimaging and postimaging clinical diagnosis
      and treatment, pain levels, and location were recorded. Pain-free survival was
      compared between treatments using a Cox proportional hazards model. RESULTS: A
      total of 202 patients with mean age 53.7 +/- 14.8 years and a male/female ratio
      of 1:1.53 were included. Of these patients, 115 presented with radiculopathy
      (57%), 56 with pelvic pain (28%), and 31 with groin pain (15%). Mean initial pain
      level was 6.9 +/- 1.9. Mean symptom duration was 4.21 +/- 5.86 years. Of these
      patients, 143 (71%) had a change in management because of MRN. After MRN,
      reduction in pain levels was observed in 21 of 32 patients receiving conservative
      treatment (66%), 42 of 67 receiving injections (63%), and 27 of 33 receiving
      surgery (82%). Follow-ups were available in 131 patients. Median pain-free
      survival was 12 months. Patients treated with surgery had significantly lower
      pain recurrence than patients receiving other treatments in the same time frame
      (hazard ratio, 3.6; 95% confidence interval, 1.4-9.2; P = 0.0061). CONCLUSIONS:
      MRN use in chronic lumbosacral and pelvic pain led to a meaningful change in
      diagnosis and treatment. After MRN, conservative treatment and injections
      provided pain relief; however, patients benefited more from surgery than from any
      other treatment.

PMID- 29581015
TI  - Suprasellar Hemangioblastoma with Reversible Edema-Like Change Along the Optic
      Tract: A Case Report and Literature Review.
AB  - BACKGROUND: Hemangioblastomas usually occur in the cerebellum and are often a
      component of von Hippel-Lindau disease. Edema-like changes along the optic tract
      are commonly observed in association with tumors in the sellar and suprasellar
      regions, such as craniopharyngiomas and pituitary adenomas. Here, we describe a
      case of sporadic suprasellar hemangioblastoma with edema-like changes along the
      optic tract that completely resolved after surgery. CASE DESCRIPTION: The patient
      was a 28-year-old woman with failing vision and a bitemporal hemianopia. Magnetic
      resonance imaging revealed a tumor accompanied by a 10-mm cyst. Fluid-attenuated
      inversion recovery axial magnetic resonance imaging revealed a hyperintense
      region along the optic tract. Other regions of the central nervous system were
      normal. Endoscopic transsphenoidal surgery was performed, and the histopathologic
      findings confirmed hemangioblastoma. Six months after surgery, the edema-like
      change along the optic tract had disappeared. The patient is doing well without
      pituitary insufficiency, pituitary hormone medications, or signs of tumor
      recurrence. In addition, the genetic test was negative for von Hippel-Lindau
      mutations. CONCLUSIONS: When examining a patient with suprasellar tumor,
      clinicians must consider the possibility of hemangioblastoma. Adequate treatment
      can improve the edematous change and visual disturbance.

PMID- 29581016
TI  - CASP8, XRCC1, WRN, NF2, and BRIP1 Polymorphisms Analysis Shows Their Genetic
      Susceptibility for Meningioma Risk and the Association with Tumor-Related
      Phenotype in a Chinese Population.
AB  - OBJECTIVE: To investigate 10 candidate single nucleotide polymorphisms (SNPs) in
      5 genes (CASP8, XRCC1, WRN, NF2, and BRIP1) to confirm the association between
      the 5 genes and the meningioma risk in a Chinese population. METHODS: We examined
      10 candidate SNPs in 5 genes (CASP8, XRCC1, WRN, NF2, and BRIP1) to confirm the
      association between the 5 genes and the meningioma risk and tumor-related
      phenotype in 433 individuals, including 215 patients with meningioma and 218
      controls. RESULTS: The polymorphisms rs4968451T>G in BRIP1 were significantly
      associated with the risk of meningioma (TT vs. TG vs. GG additive, P = 0.005;
      TT+TG vs. GG dominant, P = 0.015; TT/GT+GG recessive, P = 0.034). The significant
      association was found only in females for BRIP1 rs4968451T>G (TT+TG vs. GG
      dominant, P = 0.001; TT/GT+GG recessive, P = 0.044). We observed no significant
      association between genotypes and the meningioma risk for the other 9 SNPs.
      Through genotype-phenotype analysis, the genotype of BRIP1 rs4968451T>G was also
      strongly associated with tumor-related phenotypes, including the tumor grade and
      tumor subtypes. BRIP1 rs4968451T>G was associated with markedly grade I
      meningioma risk (TT+TG vs. GG dominant, P = 0.008; TT/GT+GG recessive, P =
      0.020). In addition, BRIP1 rs4968451T>G was associated with markedly
      meningothelial and transitional meningioma risk. Furthermore, the genotype of
      CAPS8, XRCC1, and NF2 was associated with different subtype of meningioma risk.
      CONCLUSIONS: This study indicated a role for BRIP1 gene variations in meningioma
      and may be informative for future genetic or biological studies of meningioma.
      These findings will assist in further understanding the genetic cause for
      meningiomas and guide more effective biological interventions to facilitate
      meningiomas.

PMID- 29581017
TI  - Transforaminal Endoscopic Decompression for Lumbar Spinal Stenosis: A Novel
      Surgical Technique and Clinical Outcomes.
AB  - OBJECTIVE: Transforaminal endoscopic treatment has been reported to be an
      effective treatment option in patients with lumbar disc herniation. However, it
      is rarely performed for spinal stenosis because of the limitation of endoscopic
      working mobility caused by the exiting nerve root and foraminous bony structure.
      The objective of this study was to describe a novel transforaminal endoscopic
      decompression technique for spinal stenosis and report the clinical results.
      METHODS: From October 2015 to October 2016, 30 consecutive cases were diagnosed
      as lateral recess stenosis in our institution and underwent transforaminal
      endoscopic decompression. Visual analog scale (VAS) of back and leg pain and the
      Oswestry Disability Index (ODI) were measured preoperatively and at follow-up.
      RESULTS: The mean +/- SD value of preoperative VAS leg pain score was 7.6 +/-
      1.17. The score improved to 2.2 +/- 1.11 at 1 week postoperatively, 1.73 +/- 0.96
      at 4 weeks postoperatively, and 1.63 +/- 0.95 at 26 weeks postoperatively (P <
      0.01). The mean +/- SD value of the preoperative ODI score was 65.69 +/- 14.22.
      The score improved to 24.29 +/- 11.89 at 1 week postoperatively, 21.25 +/- 9.25
      at 4 weeks postoperatively, and 15.62 +/- 10.49 at 26 weeks postoperatively (P <
      0.01). There were no patients with postoperative infection, dural tear, delayed
      neurologic deterioration, or conversion to open surgery. CONCLUSIONS:
      Transforaminal endoscopic decompression under local anesthesia could be an
      effective treatment method for the selected group of patients with spinal
      stenosis.

PMID- 29581018
TI  - Application of Morphometrics as a Predictor for Survival in Patients with
      Prostate Cancer Metastasis to the Spine.
AB  - BACKGROUND: Surgery for spinal metastases can improve survival but has high
      morbidity that can potentially diminish benefits. New objective methods of
      predicting overall survival would be beneficial for surgical decision making.
      Morphometrics quantifies patient frailty and has been successfully used to
      predict overall survival in patients with lung cancer spinal metastases. This
      study evaluated whether morphometrics can predict survival in patients with
      prostate cancer spinal metastases. METHODS: Using a retrospective registry of
      patients with spinal metastases who underwent stereotactic body radiation
      therapy, we identified patients with primary prostate cancer. Morphometric
      measurements of the psoas muscle were taken from most recent lumbar spine
      computed tomography. Patients were stratified into lowest, middle, and highest
      tertiles based on psoas muscle area. Primary outcome measure was overall survival
      from the date of computed tomography scan. RESULTS: We identified 92 patients.
      Median survival for all patients was 124 days (95% confidence interval, 98-197
      days). Patients in the smallest third for average psoas size had significantly
      shorter survival compared with patients in the largest third: 117 days versus 302
      days (hazard ratio 2.42; 95% confidence interval, 1.32-4.43; P = 0.004). Patients
      in the middle third for average psoas size also had shorter survival compared
      with patients in the largest third: 113 days versus 302 days (hazard ratio 2.31;
      95% confidence interval, 1.25-4.25; P = 0.007). CONCLUSIONS: In patients with
      prostate cancer spinal metastases, morphometric analysis of psoas muscle size can
      identify patients at risk for shorter survival. This technique can aid in
      surgical decision making by weighing expected survival and fitness versus
      potential morbidity of intervention.

PMID- 29581019
TI  - Increased Expression of Apo-J and Omi/HtrA2 After Intracerebral Hemorrhage in
      Rats.
AB  - OBJECTIVE: To investigate the changes of Apo-J and Omi/HtrA2 protein expression
      in rats with intracerebral hemorrhage. METHODS: 150 Sprague-Dawley adult rats
      were randomly divided into 3 groups: (1) normal control (NC) group, (2) sham
      group, and (3) intracerebral hemorrhage (ICH) group. The data were collected at 6
      hours, 12 hours, 1 day, 2 days, 3 days, 5 days, and 7 days. Apoptosis was
      measured by terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick
      end labeling staining. The distributions of the Apo-J and Omi/HtrA2 proteins were
      determined by immunohistochemical staining. The levels of Apo-J mRNA and
      Omi/HtrA2 mRNA expressions were examined by real-time polymerase chain reaction.
      RESULTS: Apoptosis in the ICH group was higher than in the sham and NC groups (P
      < 0.05). Both the Apo-J and Omi/HtrA2 expression levels were increased in the
      peripheral region of hemorrhage, with a peak at 3 days. The Apo-J mRNA level
      positively correlated with the HtrA2 mRNA level in the ICH group (r = 0.883, P <
      0.001). CONCLUSION: The expressions of Apo-J and Omi/HtrA2 increased in parallel
      in the peripheral region of rat cerebral hemorrhage. Local high expression of Apo
      J in the peripheral regions may play a neuroprotective role by inhibiting
      apoptosis via the Omi/HtrA2 pathway after hemorrhage.

PMID- 29581020
TI  - Results of Percutaneous Balloon Compression in Trigeminal Pain Syndromes.
AB  - OBJECTIVE: To investigate initial pain relief and subsequent recurrence after
      percutaneous balloon compression (PBC) and describe its association with the
      nature of trigeminal pain, previous procedures, or other clinical factors.
      METHODS: A total of 222 patients with medically refractory trigeminal pain
      treated with PBC at Mayo Clinic Florida between 1998 and 2017 were enrolled into
      this study. Patients were divided into those with typical trigeminal neuralgia
      (TN) and those with atypical trigeminal pain. The postprocedural rate of pain
      recurrence and associations between patient characteristics and recurrence were
      studied. RESULTS: One hundred fifty-two patients had TN and 70 patients had
      atypical pain. At the last follow-up, 158 patients had excellent pain relief, 37
      had good pain relief, 11 had fair pain relief, and 16 had poor pain relief. The
      median duration of follow-up was 31.1 months. Patients with atypical pain were
      less likely to have an excellent result compared with patients with typical pain
      (61.4% vs. 82.9%; P < 0.001). Recurrence was observed in 103 patients (46.4%) and
      was associated with previous procedures (hazard ratio, 1.658; 95% confidence
      interval, 1.09-2.49; P = 0.017). Other clinical factors were not significant.
      CONCLUSIONS: Our study demonstrates the safety and efficacy of PBC, with 88% of
      patients pain-free at last follow-up. Patients with atypical pain have worse
      outcomes, and patients with previous procedures have a higher risk of recurrence.
      Repeat surgery does not decrease efficacy. We recommend conservative parameter
      selection at the initial procedure.

PMID- 29581021
TI  - Magnetic Resonance Imaging Characteristics of Pituitary Abscess: A Review of 51
      Cases.
AB  - OBJECTIVE: To investigate pituitary abscess (PA) magnetic resonance imaging (MRI)
      features to improve the neuroradiologic and diagnostic knowledge of this rare
      disease and guide follow-up treatments. METHODS: Clinical data were collected for
      51 patients with PA, and MRI data were quantitatively reviewed in a retrospective
      analysis. Clinical factors were analyzed to investigate their relevance. RESULTS:
      PA neuroimaging showed special radiologic features, including hypointensity or
      isointensity on T1-weighted imaging (30 patients, 58.8%), isointensity or
      hyperintensity on T2-weighted imaging (39 patients, 76.5%), and disappearance of
      the posterior pituitary bright spot in most patients (44 patients, 86.3%). After
      gadolinium injection, rim or rimlike enhancement was observed in 82.4% of
      patients (n = 42). Half of those patients showed typical rim enhancement
      (profound peripheral enhancement with internal hypointensity); others showed
      atypical rim enhancement with special signs, such as enhanced, thick abscess wall
      and hyperintense flocculent or cottonlike foci within the internal hypointense
      region. Almost all patients (96.1%) presented at least 1 sign of adjacent
      anatomic structure invasion, including peripheral meninges enhancement, pituitary
      stalk thickening, and paranasal sinus mucosa enhancement. Rank correlation
      analysis of the clinical time course and MRI characteristics of PA showed a
      Spearman correlation coefficient of 0.270, indicating borderline significance (P
      = 0.055). CONCLUSIONS: Classic MRI characteristics of PA show T1 signal
      hypointensity or isointensity, T2 signal isointensity or hyperintensity, and
      peripheral rim enhancement after gadolinium injection. The MRI appearance of PA
      may reflect the abscess liquefaction and formation. Despite its profound
      significance for differential diagnosis, adjacent structure invasion is generally
      ignored by clinicians.

PMID- 29581023
TI  - Stress-induced flexibility and individuality in female and male zebra finch
      distance calls.
AB  - Vocal recognition is central to the coordination and organization of behavior in
      pair-bonding species such as zebra finches. Zebra finches' vocalizations are
      individualized and support acoustic discrimination processes. Physiological
      states - such as the ones involved in emotional stress - can modify vocal
      production and consequently the structure of vocalizations. These modifications
      might signal the state of the caller but also impair individual recognition
      processes. This may represent a signaling trade-off, especially in contexts where
      both pieces of information can be critically important, for example when mates
      use calls to reunite after social isolation. Here we study the impact of a stress
      on the individual vocal signature in both female and male zebra finch distance
      calls. We built a manually curated database of distance calls of several
      individuals (both females and males) recorded in control and stress conditions.
      The stress was induced either by social isolation of the bird or using exogenous
      corticosterone. We developed a machine learning approach to assess the impact of
      stress on the individual characterization of calls. We show that while calls'
      spectral structure is significantly modified by stress, it still allows for the
      correct classification of calls to the caller. Moreover, we also show that the
      stress-induced modification of calls' structure is not a 'general feature signal'
      that can be detected as a 'stress' signal regardless of identity. Thus, female
      and male zebra finch calls' structure show stress-induced flexibility that stays
      within the range of individual vocal signatures.

PMID- 29581022
TI  - Neuroendoscopic Cylinder Surgery and 5-Aminolevulinic Acid Photodynamic Diagnosis
      of Deep-Seated Intracranial Lesions.
AB  - BACKGROUND: Microscopic detection of intracranial brain tumors with 5
      aminolevulinic acid (5-ALA) has proven extremely useful, and reports the use of 5
      ALA have recently increased. However, few reports have described 5-ALA
      photodynamic diagnosis (PDD) using a neuroendoscope. We performed neuroendoscopic
      5-ALA PDD for various brain lesions and present a procedure using only a
      neuroendoscope. METHODS: We describe the diagnosis of 20 intracranial brain
      lesion cases with a 5-ALA-guided fluorescence endoscope. A light-emitting diode
      that emitted either white light or 400- to 410-nm violet light was attached to a
      neuroendoscope. We performed cylinder surgery with a transparent sheath under
      observation with a rigid neuroendoscope. RESULTS: Neuroendoscopic biopsies were
      performed in 11 patients, and resections were performed in 9 patients. All
      lesions were observed with a neuroendoscope under sequential white light and
      violet light. We confirmed the presence of a red fluorescent lesion under violet
      light in 15 patients, including 4 of 5 glioblastoma cases (80%); 1 of 2
      anaplastic astrocytoma cases (50%); 4 of 5 diffuse large B cell lymphoma cases
      (80%); 2 of 2 metastatic brain tumors; 1 of 1 case each of diffuse astrocytoma,
      pilocytic astrocytoma, inflammatory change, and germinoma (100%); and no cases of
      anaplastic ependymoma or cysticercosis. Pretargeted lesions were accurately
      harvested from all biopsy specimens. Gross total resection was achieved in 5 of 9
      patients using a resection procedure. CONCLUSIONS: Our described method offers a
      promising technique for achieving precise brain tumor biopsies and safe
      resection.

PMID- 29581024
TI  - Zoon politikon: The evolutionary origins of human socio-political systems.
AB  - We deploy the most up-to-date evidence available in various behavioral fields in
      support of the following hypothesis: The emergence of bipedalism and cooperative
      breeding in the hominin line, together with environmental developments that made
      a diet of meat from large animals adaptive, as well as cultural innovations in
      the form of fire, cooking, and lethal weapons, created a niche for hominins in
      which there was a significant advantage to individuals with the ability to
      communicate and persuade in a moral context. These forces added a unique
      political dimension to human social life which, through gene-culture coevolution,
      became Homo ludens-Man, the game player-with the power to conserve and transform
      the social order. Homo sapiens became, in the words of Aristotle's Nicomachean
      Ethics, a zoon politikon.

PMID- 29581025
TI  - Effect of the exploratory behaviour on a bird's ability to categorize a predator.
AB  - Despite the encountering of a predator always being extremely threatening, there
      is a significant plasticity among individuals in how they cope with such a
      situation. In laboratory experiments with wild-caught great tits (Parus major),
      we tested the effect of exploratory behaviour (performance in novel food, object
      and environment test, startle test) on the ability of individual birds to assess
      the threat represented by a predator. We presented a wooden dummy of the European
      sparrowhawk (Accipiter nisus), an extremely dangerous predator, and its visual
      modifications (chimeras), changing the beak or head to be non-threatening (those
      of a pigeon - Columba livia f. domestica). We showed that the differences between
      'slow' and 'fast explorers' are not very distinct, but that 'slow explorers'
      generally tended to be more cautious in the presence of an unmodified sparrowhawk
      dummy, while the 'fast explorers' tended to observe the dummy. On the contrary,
      'slow explorers' tended to treat both chimaeras (and the pigeon dummy as well) as
      less-threatening than 'fast explorers'. Since 'slow explorers' are usually
      considered to be more sensitive to environmental cues, it came as no surprise
      that most of them correctly assessed the unmodified sparrowhawk dummy as
      threatening, while they probably subjected the chimeras to a detailed inspection
      and were not confused by the presence of sparrowhawk features and assessed them
      as non-threatening.

PMID- 29581026
TI  - Description and phylogeny of the mitochondrial genome of Sabethes chloropterus,
      Sabethes glaucodaemon and Sabethes belisarioi (Diptera: Culicidae).
AB  - Mosquitoes as Sabethes chloropterus, Sabethes glaucodaemon, Sabethes belisarioi
      are species of medical and epidemiological importance for arboviruses
      transmission such as yellow fever and St. Louis encephalitis. Despite this, no
      information about these three species mitochondrial DNA has been found in
      literature. Our study presents a mitochondrial genome description, including
      identity, SNPs, mutation rate, and phylogeny analysis using COX1, COX2, NADH4,
      NADH5, CYOB genes. The Sa. chloropterus, Sa. glaucodaemon and Sa. belisaroi
      mitochondrial genome sizes 15.609 bp, 15.620 bp, 15.907 bp, respectively, with 37
      functional genes, presenting about 4.982 single nucleotide polymorphisms and
      13.291 identical sites between them, besides all genes with dN/dS < 1 ratio, and
      also a greater approximation between Sa. glaucodaemon and Sa. chloropterus than
      with Sa. belisarioi. Due to the importance of mitochondrial DNA for population
      structure studies, evolution, and others, we expect that this data can contribute
      to other studies related to these mosquitoes and their viruses.

PMID- 29581027
TI  - Improved reactive nanoparticles to treat dentin hypersensitivity.
AB  - : The aim of this study was to evaluate the effectiveness of different
      nanoparticles-based solutions for dentin permeability reduction and to determine
      the viscoelastic performance of cervical dentin after their application. Four
      experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded
      polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to
      facilitate the occlusion and the reduction of the fluid flow at the dentinal
      tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid
      filtration. Field emission scanning electron microscopy, energy dispersive
      analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss
      modulus and tan delta (delta) were assessed. Doxycycline-loaded NPs impaired
      tubule occlusion and fluid flow reduction trough dentin. Tubules were 100%
      occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed
      at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest
      reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs,
      complex modulus values attained at intertubular and peritubular dentin were
      higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed
      to fasten active dentin remodeling, with increased maturity and high mechanical
      properties. Zinc-based nanoparticles are then proposed for effective dentin
      remineralization and tubular occlusion. Further research to finally prove for
      clinical benefits in patients with dentin hypersensitivity using Zn-doped
      nanoparticles is encouraged. STATEMENT OF SIGNIFICANCE: Erosion from acids
      provokes dentin hypersensitivity (DH) which presents with intense pain of short
      duration. Open dentinal tubules and demineralization favor DH. Nanogels based on
      Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid
      flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate
      deposits. When treating dentin with Zn-nanoparticles, complex modulus values
      attained at intertubular and peritubular dentin were higher than those obtained
      after applying Ca-nanoparticles. Zn-nanoparticles are then supposed to fasten
      active dentin remodeling, with increased maturity and high mechanical properties.
      Zinc-based nanogels are, therefore, proposed for effective dentin
      remineralization and tubular occlusion. Further research to finally prove for
      clinical benefits in patients with dentin hypersensitivity using Zn-doped
      nanogels is encouraged.

PMID- 29581028
TI  - Nanoemulsions containing Cymbopogon flexuosus essential oil: Development,
      characterization, stability study and evaluation of antimicrobial and antibiofilm
      activities.
AB  - The increase of microbial resistance generates the search for new substances with
      antimicrobial potential. The essential oil of Cymbopogon flexuosus (Lemongrass)
      stands out in the literature for its antimicrobial, insecticide and antioxidant
      properties, but it has high volatilization and low stability, and the
      nanoencapsulation of this oil could be an alternative to overcome these
      limitations. Thus, the objective of this study was to develop, for the first
      time, nanoemulsions containing the essential oil of C. flexuosus, through a
      method that does not use organic solvent and with temperature control to avoid
      the volatilization of the oil, characterize and evaluate of stability and the
      antimicrobial and antibiofilm activities of these nanoemulsions. Nanoemulsions
      presented adequate physicochemical characteristics (average size less than 200
      nm, polydispersity index less than 0.3, negative zeta potential and acid pH)
      which were maintained during 90 days of storage, and the nanoencapsulation of the
      C. flexuosus oil enhanced its therapeutic efficacy against the microorganisms
      evaluated in this study compared to the free oil. These results are very
      promising because among the microorganisms that the nanoemulsion containing C.
      flexuosus was able to inhibit the formation of biofilm are the bacteria
      Pseudomonas aeruginosa and Staphylococcus aureus, which were recently listed by
      the World Health Organization as priority pathogens for development of new
      antibiotics.

PMID- 29581029
TI  - Identification of first-stage dorsal-spined lungworm larvae of Tunisian barbary
      red deer: First report of Varestrongylus sagittatus and Elaphostrongylus cervi in
      Africa.
AB  - Barbary red deer (Cervus elaphus barbarus) is a protected rare subspecies of red
      deer. The study of its Protostrongylidae fauna based only on sporadic necropsy of
      naturally dead animals is difficult. Therefore diagnosis of lungworms rely mainly
      on the identification of the first stage larvae (L1). The L1 of the different
      species are not readily diagnosed on morphological basis since much variation is
      recorded within and among dorsal-spined larvae belonging to various species. The
      aim of this study was to identify the dorsal-spined lungworm larvae of the
      Barbary red deer. A discriminant function was established, using the measurements
      of L1 lungworms recorded from red deer in the literature, then applied to
      identify 220 dorsal-spined larvae extracted from 25 Tunisian Barbary red deer
      fresh fecal samples. Also the ITS2 region of rDNA of four pools of larvae (n = 25
      60) were amplified, sequenced and analyzed. Using discriminant analysis of
      morphological traits, Elaphostrongylus cervi and Varestongylus sagittatus were
      identified. Molecular identification confirmed the presence of E. cervi which is
      the most prevalent species. This study represents the first identification of V.
      sagittatus and E. cervi in North Africa.

PMID- 29581030
TI  - Detection of Neospora caninum DNA by polymerase chain reaction in bats from
      Southern China.
AB  - Neospora caninum is an intracellular protozoan that infects many domestic and
      wild animals. Domestic dogs and other canids function as definitive hosts, while
      other mammals serve as natural intermediate hosts. In the present study, the
      brain tissues of bats collected in Yunnan Province, Southern China were tested by
      N. caninum specific-nested PCR, targeting the Nc-5 gene and the internal
      transcribed spacer 1 (ITS1) region of the ribosomal DNA to determine whether bats
      could be infected with N. caninum. N. caninum DNA was detected in 1.8% (4/227) of
      bats, i.e., 1.7% (1/60) in Rousettus leschenaultia, 1.7% (1/58) in Hipposideros
      pomona, 2.9% (2/69) in Rhinolophus pusillus, and none (0/40) in Myotis
      daubentoniid. The findings of the present study are only the first indication
      that bats could serve as an intermediate host, and further studies are necessary
      to confirm whether bats are involved in the transmission of N. caninum
      infections.

PMID- 29581031
TI  - IL-7-induced phosphorylation of the adaptor Crk-like and other targets.
AB  - IL-7 is required for T cell differentiation and mature T cell homeostasis and
      promotes pro-B cell proliferation and survival. Tyrosine phosphorylation plays a
      central role in IL-7 signaling. We identified by two-dimensional electrophoresis
      followed by anti-phosphotyrosine immunoblotting and mass spectrometry sixteen
      tyrosine phosphorylated proteins from the IL-7-dependent cell line D1. IL-7
      stimulation induced the phosphorylation of the proteins STI1, ATIC and hnRNPH,
      involved in pathways related to survival, proliferation and gene expression,
      respectively, and increased the phosphorylation of CrkL, a member of a family of
      adaptors including the highly homologous Crk isoforms CrkII and CrkI, important
      in multiple signaling pathways. We observed an increased phosphorylation of CrkL
      in murine pro-B cells and in murine and human T cells. In addition, IL-7
      increased the association of CrkL with the transcription factor Stat5, essential
      for IL-7 pro-survival activity. The selective tyrosine kinase inhibitor Imatinib.
      counteracted the IL-7 pro-survival effect in D1 cells and decreased CrkL
      phosphorylation. These data suggested that CrkL could play a pro-survival role in
      IL-7-mediated signaling. We observed that pro-B cells also expressed, in addition
      to CrkL, the Crk isoforms CrkII and CrkI and therefore utilized pro-B cells
      conditionally deficient in all three to evaluate the role of these proteins. The
      observation that the IL-7 pro-survival effect was reduced in Crk/CrkL
      conditionally-deficient pro-B cells further pointed to a pro-survival role of
      these adaptors. To further evaluate the role of these proteins, gene expression
      studies were performed in Crk/CrkL conditionally-deficient pro-B cells. IL-7
      decreased the transcription of the receptor LAIR1, which inhibits B cell
      proliferation, in a Crk/CrkL-dependent manner, suggesting that the Crk family of
      proteins may promote pro-B cell proliferation. Our data contribute to the
      understanding of IL-7 signaling and suggest the involvement of Crk family
      proteins in pathways promoting survival and proliferation.

PMID- 29581032
TI  - Enhancing the performance of Escherichia coli-inoculated microbial fuel cells by
      introduction of the phenazine-1-carboxylic acid pathway.
AB  - Microbial fuel cells (MFCs) are a renewable green energy source that uses
      microorganisms to catalytically convert chemical energy into electrical energy.
      The efficiency of extracellular electron transfer (EET) from the microbe cell to
      the anode electrode plays a key role in the MFC. However, the insulating
      properties of the cell membrane limit the efficiency of EET. Herein, EET
      efficiency was improved by introducing a phenazine synthesis pathway into
      Escherichia coli. Through the heterologous expression of phzA1B1C1D1E1F1G1,
      phenazine-1-carboxylic acid production increased, and the maximum power density
      increased from 16.7 mW/m2 to 181.1 mW/m2. Furthermore, the charge transfer
      resistance of 6.7 Omega decreased to 4.2 Omega, which reflected the enhancement
      of the EET efficiency and the electricity power output. Our results imply that
      introducing a heterologous electron shuttle into E. coli could be an efficient
      approach to improving the EET efficiency and performance of an MFC.

PMID- 29581033
TI  - Production of foot-and-mouth disease virus capsid proteins by the TEV protease.
AB  - Protective immunity to viral pathogens often includes production of neutralizing
      antibodies to virus capsid proteins. Many viruses produce capsid proteins by
      expressing a precursor polyprotein and related protease from a single open
      reading frame. The foot-and-mouth disease virus (FMDV) expresses a 3C protease
      (3Cpro) that cleaves a P1 polyprotein intermediate into individual capsid
      proteins, but the FMDV 3Cpro also degrades many host cell proteins and reduces
      the viability of host cells, including subunit vaccine production cells. To
      overcome the limitations of using the a wild-type 3Cpro in FMDV subunit vaccine
      expression systems, we altered the protease restriction sequences within a FMDV
      P1 polyprotein to enable production of FMDV capsid proteins by the Tobacco Etch
      Virus NIa protease (TEVpro). Separate TEVpro and modified FMDV P1 proteins were
      produced from a single open reading frame by an intervening FMDV 2A sequence. The
      modified FMDV P1 polyprotein was successfully processed by the TEVpro in both
      mammalian and bacterial cells. More broadly, this method of polyprotein
      production and processing may be adapted to other recombinant expression systems,
      especially plant-based expression.

PMID- 29581035
TI  - Validation of the Edmonton Symptom Assessment System: Ascites Modification.
AB  - CONTEXT: Few patient-reported outcomes are available to measure the symptoms
      associated with malignant-related ascites in patient care and clinical research.
      Although the Edmonton Symptom Assessment System: Ascites Modification (ESAS:AM)
      is a brief tool to measure symptoms associated with malignant-related ascites, it
      remains to be fully validated. OBJECTIVES: The objective of the study was to
      validate the ESAS:AM in Japanese cancer patients. METHODS: We assessed the
      internal consistency, test-retest reliability, concurrent validity, and construct
      validity in 292 Japanese adult patients with cancer. They completed Japanese
      versions of the ESAS:AM, M.D. Anderson Symptom Inventory, European Organization
      for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and
      abdominal pain/ascites subscales of the EORTC Core Quality of Life Questionnaire,
      26-item pancreatic cancer module. RESULTS: Cronbach's alpha coefficient of the
      ESAS:AM was 0.89. The intraclass correlation coefficient on test-retest
      examination of its total score was 0.93 (P < 0.001). Pearson correlation
      coefficients of the total score of the ESAS:AM with the total score of the M.D.
      Anderson Symptom Inventory and abdominal pain/ascites subscales of the EORTC Core
      Quality of Life Questionnaire, 26-item pancreatic cancer module ranged from 0.44
      to 0.81 (P < 0.001) and those with global health status/quality of life and
      functional subscales of the European Organization for Research and Treatment of
      Cancer Quality of Life Questionnaire-Core 30 ranged from -0.40 to -0.61 (P <
      0.001). The total scores of the ESAS:AM were significantly higher in 20 patients
      with symptomatic ascites (34 [SD, 26]) than 267 patients without symptomatic
      ascites (23 [SD, 19]) (P = 0.018). CONCLUSION: The ESAS:AM is a reliable and
      valid tool for measuring symptoms associated with malignant-related ascites and
      can be used in daily patient care and future epidemiological studies and clinical
      trials.

PMID- 29581034
TI  - Preference for Palliative Care in Cancer Patients: Are Men and Women Alike?
AB  - CONTEXT: Men and those with low educational attainment are less likely to receive
      palliative care. Understanding these disparities is a high priority issue.
      OBJECTIVES: In this study of advanced cancer patients, we hypothesized that men
      and those with lower levels of educational attainment would have less favorable
      attitudes toward palliative care. METHODS: We performed a cross-sectional
      analysis of data collected from 383 patients at study entry in the Values and
      Options in Cancer Care (VOICE) clinical trial. Patients were asked about their
      preferences for palliative care if their oncologist informed them that further
      treatment would not be helpful. Palliative care was defined as "comfort care"
      that focuses on "quality of life, but not a cure." Response options were
      definitely no, possibly no, unsure, possibly yes, and definitely yes. Those
      preferring palliative care (definitely or possibly yes) were compared to all
      others. Predictors were patient gender and education level. Covariates included
      age, race, disease aggressiveness, and financial strain. RESULTS: Women were more
      likely [odds ratio (95% CI)] than men to prefer palliative care [3.07 (1.80
      5.23)]. The effect of education on preferences for palliative care was not
      statistically significant [0.85 (0.48-1.48)]. CONCLUSION: Significant gender
      differences in patients' preferences for palliative care could partially account
      for gender disparities in end-of-life care. Interventions to promote palliative
      care among men could reduce these disparities.

PMID- 29581036
TI  - Let's Work Together: Collaborative Research Is Needed to Overcome Difficulty
      Enrolling Families for Bereaved Sibling Research.

PMID- 29581037
TI  - The Association of Body Mass Index and 20-Year All-Cause Mortality Among Patients
      With Stable Coronary Artery Disease.
AB  - BACKGROUND: Limited data exist regarding the long-term association of body mass
      index (BMI) and all-cause mortality among patients with stable coronary artery
      disease (CAD). Accordingly, the aim of this study is to explore the association
      between BMI and long-term all-cause mortality among patients with stable CAD.
      METHODS: Our study included 15,357 patients with stable CAD who were enrolled in
      the Bezafibrate Infarction Prevention (BIP) registry between February, 1990 and
      October1992, and subsequently followed-up through December 2014. RESULTS: 5051
      (33%) patients were classified as normal weight (BMI 18.5-24.99kg/m2), while 7841
      (51%) patients classified as overweight (BMI 25-29.99kg/m2), and 2465 (16%) as
      obese (BMI>=30). Kaplan-Meier survival analysis showed that at 20 years of follow
      up the rate of all-cause mortality was significantly higher among obese patients
      (67%) compared to overweight (61%) and normal weight (61%); log rank p-value for
      the overall difference <0.001. Multivariable analysis showed that obese patients
      had an independently 12% greater mortality risk compared to normal weight
      patients (HR=1.12; 95% CI 1.02-1.23; p=0.02), whereas, overweight patients
      experienced a similar mortality risk as normal weight patients (HR=0.99; 95% CI
      0.92-1.06; p=0.76). The mortality risk associated with obesity was pronounced
      among patients younger than 65 years (p-value for interaction<0.05). CONCLUSIONS:
      Our findings indicate that obesity is independently associated with increased
      risk for long-term mortality among patients with stable coronary artery disease,
      whereas overweight does not appear to confer an additional risk in this
      population.

PMID- 29581038
TI  - Levosimendan Following Cardiac Surgery.
AB  - A best evidence topic was written to address if perioperative levosimendan
      improves mortality following cardiac surgery. Fourteen papers represented the
      best available evidence. An older meta-analysis summarising 11 of these trials
      concluded that there were fewer deaths in the levosimendan group compared to the
      control group (OR 0.41, p <0.001) however, this was driven by the results of
      three included trials by the same author. Three larger and more recent randomised
      controlled trials failed to demonstrate significant differences in mortality. We
      conclude that levosimendan lacks robust evidence to substantiate claims of
      mortality benefit in cardiac surgery patients and should not be used routinely in
      such patients.

PMID- 29581039
TI  - Arterial Access for Invasive Coronary Angiography: The 'Left Backhander'.

PMID- 29581040
TI  - Female False Positive Exercise Stress ECG Testing - Fact Verses Fiction.
AB  - BACKGROUND: Exercise stress testing is a well validated cardiovascular
      investigation. Accuracy for treadmill stress electrocardiograph (ECG) testing has
      been documented at 60%. False positive stress ECGs (exercise ECG changes with non
      obstructive disease on anatomical testing) are common, especially in women,
      limiting the effectiveness of the test. This study investigates the incidence and
      predictors of false positive stress ECG findings, referenced against stress
      echocardiography (SE) as a standard. METHODS: Stress echocardiography was
      performed using the Bruce treadmill protocol. False positive stress ECG tests
      were defined as greater than 1mm of ST depression on ECG during exertion, without
      pain, with a normal SE. Potential causes for false positive tests were recorded
      before the test. RESULTS: Three thousand consecutive negative stress
      echocardiograms (1036 females, 34.5%) were analysed (age 59+/-14 years. False
      positive (F+) stress ECGs were documented in 565/3000 tests (18.8%). F+ stress
      ECGs were equally prevalent in females (194/1036, 18.7%) and males (371/1964,
      18.9%, p=0.85 for the difference). Potential causes (hypertension, left
      ventricular hypertrophy, known coronary disease, arrhythmia, diabetes mellitus,
      valvular heart disease) were recorded in 36/194 (18.6%) of the female F+ ECG
      tests and 249/371 (68.2%) of the male F+ ECG tests (p<0.0001 for the difference).
      CONCLUSIONS: These data suggest that F+ stress ECG tests are frequent and equally
      common in women and men. However, most F+ stress ECGs in men can be predicted
      before the test, while most in women cannot. Being female may be a risk factor in
      itself. These data reinforce the value of stress imaging, particularly in women.

PMID- 29581041
TI  - Titania and silica nanoparticles coupled to Chlorin e6 for anti-cancer
      photodynamic therapy.
AB  - In this study, light-sensitive photosensitizers (Chlorin e6, Ce6) were linked to
      TiO2 and SiO2 nanoparticles (NPs) in order to develop new kinds of NP-based drug
      delivery systems for cancer treatment by PDT. TiO2 or SiO2 NPs were modified
      either by the growth of a polysiloxane layer constituted of two silane reagents
      ((3-aminopropyl)triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS))
      around the core (PEGylated NPs: TiO2@4Si-Ce6-PEG, SiO2@4Si-Ce6-PEG) or simply
      modified by APTES alone (APTES-modified NPs: TiO2-APTES-Ce6, SiO2-APTES-Ce6). Ce6
      was covalently attached onto the modified TiO2 and SiO2 NPs via an amide bond.
      The absorption profile of the hybridized NPs was extended to the visible region
      of the light. The physicochemical properties of these NPs were explored by TEM,
      HR-TEM, XRD, FTIR and zeta potential. The photophysical characteristics including
      the light absorption, the fluorescence properties and the production reactive
      oxygen species (1O2 and HO) were also addressed. In vitro experiments on
      glioblastoma U87 cells were performed to evaluate the photodynamic efficiency of
      the new hybridized NPs. The cells were exposed to different concentrations of NPs
      and illuminated (lambdaexc = 652 nm, fluence rate 10 J/cm2). In contrast to the
      PEGylated NPs, the APTES-modified nanosystems were found to be more efficient for
      PDT. An interesting photodynamic effect was observed in the case of TiO2-APTES
      Ce6 NPs. After illumination, the viability of U87 was decreased by 89% when they
      were exposed to 200 MUg/mL of TiO2-APTES-Ce6 NPs, which corresponds to 0.22 MUM
      of Ce6. The same effect can be obtained with free photosensitizer but using a
      higher concentration of 10 MUM of Ce6.

PMID- 29581042
TI  - Using Appendicitis to Improve Estimates of Childhood Medicaid Participation
      Rates.
AB  - OBJECTIVE: Administrative data are often used to estimate state
      Medicaid/Children's Health Insurance Program duration of enrollment and insurance
      continuity, but they are generally not used to estimate participation (the
      fraction of eligible children enrolled) because administrative data do not
      include reasons for disenrollment and cannot observe eligible never-enrolled
      children, causing estimates of eligible unenrolled to be inaccurate. Analysts are
      therefore forced to either utilize survey information that is not generally
      linkable to administrative claims or rely on duration and continuity measures
      derived from administrative data and forgo estimating claims-based participation.
      We introduce appendectomy-based participation (ABP) to estimate statewide
      participation rates using claims by taking advantage of a natural experiment
      around statewide appendicitis admissions to improve the accuracy of participation
      rate estimates. METHODS: We used Medicaid Analytic eXtract (MAX) for 2008-2010;
      and the American Community Survey for 2008-2010 from 43 states to calculate ABP,
      continuity ratio, duration, and participation based on the American Community
      Survey (ACS). RESULTS: In the validation study, median participation rate using
      ABP was 86% versus 87% for ACS-based participation estimates using logical edits
      and 84% without logical edits. Correlations between ABP and ACS with or without
      logical edits was 0.86 (P < .0001). Using regression analysis, ABP alone was a
      significant predictor of ACS (P < .0001) with or without logical edits, and
      adding duration and/or the continuity ratio did not significantly improve the
      model. CONCLUSION: Using the ABP rate derived from administrative claims (MAX) is
      a valid method to estimate statewide public insurance participation rates in
      children.

PMID- 29581043
TI  - Combinations of nanovesicles and physical methods for enhanced transdermal
      delivery of a model hydrophilic drug.
AB  - Here, we combined lipid nanovesicles (ethosomes, liposomes) as the drug carrier
      systems with two physical methods (electroporation, sonoporation) to enhance
      transdermal delivery of a hydrophilic model molecule, calcein. First, using
      different formulations, ethosomes greatly enhanced calcein permeation by passive
      diffusion compared to liposomes and calcein in buffer, which is most likely due
      to a synergism between the ethanol action on the stratum corneum lipids and the
      penetration of the elastic vesicles. Liposomes permeated poorly through the skin
      and, as also suggested by other authors, seem to remain confined to the outer
      layers of the skin. By creating localized effects, liposomes would be better
      suited to topical dermal delivery than transdermal delivery. Using sonoporation
      as the physical enhancement method, sonication (5 min) showed improvement over
      passive diffusion; however, only for the ethosome formulation, and not for
      solution and liposomes. Similarly, electroporation greatly enhanced delivery of
      calcein, which was again more pronounced for ethosomes than liposomes and calcein
      in buffer. Finally, three different transdermal delivery enhancement methods were
      coupled, using ethosomes as carriers, along with both electroporation and
      sonoporation, to investigate the potential for synergistic effects. However,
      these combinations failed to achieve not only synergistic effects, but also
      additive effects. Nevertheless, combination of the ethosome formulation of
      calcein with either of electroporation or sonoporation achieves significant
      enhancement of transdermal molecular delivery being safe for potential clinical
      use.

PMID- 29581044
TI  - Autologous falciform ligament graft as A substitute for mesentericoportal vein
      reconstruction in pancreaticoduodenectomy.
AB  - OBJECTIVE: To evaluate the falciform ligament as an autologous substitute for
      mesentericoportal vein reconstruction during pancreaticoduodenectomy. BACKGROUND:
      Mesentericoportal vein reconstruction was needed in some certain cases during
      pancreaticoduodenectomy, and a rapidly available substitute was required.
      METHODS: The falciform ligament was used as an autologous substitute during
      pancreaticoduodenectomy in 6 patients between June 2016 and May 2017.
      Anticoagulation was not performed at any stage and venous patency was estimated
      by Color-Doppler ultrasonography and contrast-enhanced computed tomography.
      RESULTS: 6 patients underwent vascular resection during pancreaticoduodenectomy
      for malignant tumors. The falciform ligament graft, with a mean length of 26 mm
      (10-40), was immediately harvested and used as a lateral patch for reconstruction
      of the mesentericoportal vein (n = 6). Severe morbidity included Clavien grade
      III complications occurred in 1(16.7%) patients but there was no graft-related
      complications. Histological vascular invasion was present in all the patients (n
      = 6, 100%), and all had an R0 resection (100%). All venous reconstructions were
      patent (100%) after a mean follow-up of 12 (6-16) months. CONCLUSIONS: An
      autologous falciform ligament graft can be safely used as a lateral substitute
      for mesentericoportal vein reconstruction during pancreaticoduodenectomy; this
      could help improve the radical resection rate of malignant tumors when
      oncologically required.

PMID- 29581045
TI  - Consensus views on the optimum training curriculum for advanced minimally
      invasive surgery: A delphi study.
AB  - INTRODUCTION: There has been a wide uptake in the use of Minimal Invasive Surgery
      (MIS) globally across different surgical specialties. Whilst evidence exists for
      a structured training curriculum for basic laparoscopic surgery, there is little
      agreement on a complete framework for an advanced MIS training curriculum,
      defining the essential elements of the curriculum including the optimal
      assessment methods. The aim of this study is to obtain a consensus on the
      essential elements of a training curriculum for advanced MIS. MATERIALS AND
      METHODS: A Delphi study was carried out involving 57 international experts in
      advanced MIS across different surgical specialties. A three round survey was
      conducted to reach consensus on the essential domains of a curriculum. This
      included defining the learners, trainers and training centres; curriculum content
      and competency based assessment. RESULTS: Unanimous agreement was reached for the
      completion of basic laparoscopic training before entry into advanced training. A
      trainer should have reached competency in advanced MIS and attended a 'Train the
      trainer' course. The curriculum should be delivered as modular training,
      including a multi-modal approach with a structured clinical proctorship
      programme. Formative assessment was considered as an integral part of learning
      and should be performed using objective work based assessment tools such as
      global assessment scale (GAS) forms. Accreditation in advanced MIS can be
      achieved by objective assessment of technical performance of unedited videos in
      addition to key clinical performance outcomes. CONCLUSION: A consensus on the
      framework of an advanced MIS training curriculum has been achieved defining the
      essential elements of entry criteria, selection of trainers and training units
      and curriculum content. Multimodal learning, clinical proctorship programme and
      competency based assessment are integral parts of the curriculum.

PMID- 29581046
TI  - The outcome of A. Double mesh intraperitoneal repair for complex ventral hernia:
      A retrospective cohort study.
AB  - BACKGROUND: Complex ventral hernia is a challenging surgical entity, commonly
      attended with huge defect, loss of domain and possible soft tissue infection. It
      is difficult to repair, especially with multiple recurrences. Numerous methods of
      repair have been described with no evidence-based data available to prefer one
      method over the other. The purpose of this study is to determine the long-term
      outcome of the proposed new modification of intraperitoneal mesh repair procedure
      in complex ventral hernia. MATERIALS AND METHODS: This is a single-center
      retrospective analysis utilizing the prospectively-maintained dataset in our
      institution during the study period between January 2003 and June 2017. Patients
      who fit the inclusion criteria of having a complex ventral hernia, whether de
      novo or recurrent and were subjected to A. Double Mesh Intraperitoneal Repair
      (ADMIR) procedure were included in the study. Patients were followed up till
      recurrence or lost to follow through a period ranging from 6 to 174 months (mean:
      142.96 +/- SE: 11.91). RESULTS: Forty-nine cases were included in this study (38
      females and 11 males) with a female to male ratio of 3.5:1. The age range was
      from 28 to 81 years (mean 49 +/- 12.4). BMI range from 25 to 42 (mean 33.6 +/-
      5.42). The ratio between the hernia sac volume and abdominal cavity volume was
      more than 20% in 12 patients (24.5%), who were subjected to preoperative
      progressive pneumoperitoneum (PPP) for an average period of two weeks. Hernias
      were recurrent in 28 cases (57%) and associated comorbidities were observed in 29
      patients (63%). Postoperative complications occurred in 19 patients (38.7%),
      among them only 2 patients developed recurrence (4%) after a mean follow up
      period of 142 months. Five patients were lost to follow and were included in the
      Kaplan and Meier survival analysis. CONCLUSIONS: ADMIR procedure is successful
      for the repair of complex ventral hernias as it is applicable to all sites of
      ventral hernias. The mesh is tension free hidden within the abdomen allowing for
      early mobilization and the complications rate is acceptable with low recurrence
      rate.

PMID- 29581047
TI  - Results of subclavian to carotid artery bypass for occlusive disease of the
      common carotid artery: A retrospective cohort study.
AB  - BACKGROUND: Optimal treatment of significant atherosclerosis of the common
      carotid artery (CCA) is not well-defined. The purpose of this study was to
      evaluate the long-term results of prosthetic subclavian to carotid bypass for
      occlusive disease of the CCA. MATERIAL AND METHODS: From January 1994 to December
      2015, 45 patients, mean age 67 years, underwent an ipsilateral subclavian to
      carotid bypass for occlusive disease of the CCA. Thirty-eight patients (84%)
      presented with neurologic symptoms, including transitory ischemic attacks in 29
      cases and minor strokes in 9 cases. The graft material consisted of a 7 mm
      polytetrafluoroethylene conduit, and the distal anastomosis was done on the
      carotid bulb in 21 patients, on the internal carotid artery in 19 cases, and on
      the distal CCA in 5 cases. Median length of follow-up was 58 months. Study
      endpoints were the combined postoperative stroke/mortality rate, graft infection,
      overall late survival, freedom from ipsilateral stroke, and graft patency.
      RESULTS: Postoperative stroke/mortality rate was 2%. No graft infection was
      observed throughout follow-up. At 60 months, overall survival, freedom from
      stroke, and graft patency were 71% (standard error [SE] = 0.07), 98% (SE = 0.02),
      and 95.5% (SE = 0.06), respectively. CONCLUSIONS: Subclavian to carotid bypass
      allows very good patency rates and excellent protection from postoperative and
      late stroke, remaining a benchmark for any other treatment method.

PMID- 29581048
TI  - What risk of endocarditis is low enough to justify the omission of
      transoesophageal echocardiography in Staphylococcus aureus bacteraemia? A
      narrative review.
AB  - BACKGROUND: Recent criteria which can identify patients with Staphylococcus
      aureus bacteraemia (SAB) who are at very low risk of endocarditis raise the
      question of whether transoesophageal echocardiography (TOE) is appropriate for
      these patients. AIMS: To estimate the probability of occult endocarditis
      complicating SAB below which a TOE-guided treatment strategy no longer offers the
      best 180-day survival, and to examine the key uncertainties affecting this
      result. SOURCES: Estimates of the parameters required to calculate the Pauker
      Kassirer testing threshold were identified from studies published prior to 1 June
      2017 using a composite search strategy that involved a systematic search for
      relevant controlled trials and guidelines, followed by a non-systematic iterative
      search of the observational literature. CONTENT: Estimates of the necessary
      parameters were generally consistent across the literature with the exception of
      the procedural mortality of TOE. In our base-case scenario (TOE mortality 0.1%),
      the testing threshold for TOE in apparently uncomplicated SAB was a 1.1%
      probability of occult endocarditis. Sensitivity analyses revealed that the
      procedural mortality of TOE was a key uncertainty affecting estimates of the
      testing threshold. IMPLICATIONS: None of the available clinical tools can place
      patients with SAB below this probability of endocarditis with 95% confidence.
      Future work in this area should concentrate on improving the precision of these
      tools and on exploring the value of alternative echocardiography strategies. In
      addition, a better understanding of the harms of TOE is required to ensure that
      recommendations regarding the role of this investigation in the management of
      patients with SAB are appropriate.

PMID- 29581049
TI  - Towards precision medicine in sepsis: a position paper from the European Society
      of Clinical Microbiology and Infectious Diseases.
AB  - BACKGROUND: Our current understanding of the pathophysiology and management of
      sepsis is associated with a lack of progress in clinical trials, which partly
      reflects insufficient appreciation of the heterogeneity of this syndrome.
      Consequently, more patient-specific approaches to treatment should be explored.
      AIMS: To summarize the current evidence on precision medicine in sepsis, with an
      emphasis on translation from theory to clinical practice. A secondary objective
      is to develop a framework enclosing recommendations on management and priorities
      for further research. SOURCES: A global search strategy was performed in the
      MEDLINE database through the PubMed search engine (last search December 2017). No
      restrictions of study design, time, or language were imposed. CONTENT: The focus
      of this Position Paper is on the interplay between therapies, pathogens, and the
      host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood
      cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as
      targeted antibiotic treatment. Other topics include the disruption of host immune
      system and the use of biomarkers in sepsis management, patient stratification,
      and future clinical trial design. Lastly, personalized antibiotic treatment and
      stewardship are addressed (Fig. 1). IMPLICATIONS: A road map provides
      recommendations and future perspectives. RDTs and identifying drug-response
      phenotypes are clear challenges. The next step will be the implementation of
      precision medicine to sepsis management, based on theranostic methodology. This
      highly individualized approach will be essential for the design of novel clinical
      trials and improvement of care pathways.

PMID- 29581050
TI  - Topography imaging of herpesvirus in native condition using atomic force
      microscopy.

PMID- 29581051
TI  - Febrile illness in Asia: gaps in epidemiology, diagnosis and management for
      informing health policy.
AB  - BACKGROUND: Increasing evidence is becoming available on the aetiology and
      management of fevers in Asia; the importance of these fevers has increased with
      the decline in the incidence of malaria. AIMS: To conduct a narrative review of
      the epidemiology and management of fevers in South and South-East Asia and to
      highlight gaps in our knowledge that impair evidence-based health policy
      decisions. SOURCES: A narrative review of papers published since 2012 on
      developments in fever epidemiology, diagnosis and treatment in South and South
      East Asia. The papers that the authors felt were pivotal, from their personal
      perspectives, are discussed. CONTENT: We identified 100 studies. Among the 30
      studies (30%)-including both children and adults-that investigated three or more
      pathogens, the most frequently reported fever aetiology was dengue (reported by
      15, 50%), followed by leptospirosis (eight, 27%), scrub typhus (seven, 23%) and
      Salmonella serovar Typhi (six, 20%). Among four studies investigating three or
      more pathogens in children, dengue and Staphylococcus aureus were the most
      frequent, followed by non-typhoidal Salmonella spp, Streptococcus pneumoniae,
      Salmonella serovar Typhi, and Orientia tsutsugamushi. Increased awareness is
      needed that rickettsial pathogens are common but do not respond to
      cephalosporins, and that alternative therapies, such as tetracyclines, are
      required. IMPLICATIONS: Many key gaps remain, and consensus guidelines for study
      design are needed to aid comparative understanding of the epidemiology of fevers.
      More investment in developing accurate and affordable diagnostic tests for rural
      Asia and independent evaluation of those already on the market are needed.
      Treatment algorithms, including simple biomarker assays, appropriate for
      empirical therapy of fevers in different areas of rural Asia should be a major
      aim of fever research. Enhanced antimicrobial resistance (AMR) surveillance and
      openly accessible databases of geography-specific AMR data would inform policy on
      empirical and specific therapy. More investment in innovative strategies
      facilitating infectious disease surveillance in remote rural communities would be
      an important component of poverty reduction and improving public health.

PMID- 29581052
TI  - Four-year safety follow-up of the tetravalent dengue vaccine CYD-TDV.

PMID- 29581053
TI  - Prevalence and clinical significance of respiratory viruses and bacteria detected
      in tuberculosis patients compared to household contact controls in Tanzania: a
      cohort study.
AB  - OBJECTIVES: To describe the prevalence of respiratory pathogens in tuberculosis
      (TB) patients and in their household contact controls, and to determine the
      clinical significance of respiratory pathogens in TB patients. METHODS: We
      studied 489 smear-positive adult TB patients and 305 household contact controls
      without TB with nasopharyngeal swab samples within an ongoing prospective cohort
      study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real
      time PCR to detect 16 respiratory viruses and seven bacterial pathogens from
      nasopharyngeal swabs. RESULTS: The median age of the study participants was 33
      years; 61% (484/794) were men, and 21% (168/794) were HIV-positive. TB patients
      had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305).
      Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95%CI 17.7
      23.3%) and of bacterial pathogens 38.2% (303/794; 95%CI 34.9-41.6%). TB patients
      and controls did not differ in the prevalence of respiratory viruses (Odds Ratio
      [OR] 1.00, 95%CI 0.71-1.44), but respiratory bacteria were less frequently
      detected in TB patients (OR 0.70, 95%CI 0.53-0.94). TB patients with both
      respiratory viruses and respiratory bacteria were likely to have more severe
      disease (adjusted OR [aOR] 1.6, 95%CI 1.1-2.4; p 0.011). TB patients with
      respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95%CI
      0.93-2.7; p 0.089). CONCLUSIONS: Respiratory viruses are common for both TB
      patients and household controls. TB patients may present with more severe TB
      disease, particularly when they are co-infected with both bacteria and viruses.

PMID- 29581054
TI  - Typing of vancomycin-resistant enterococci with MALDI-TOF mass spectrometry in a
      nosocomial outbreak setting.
AB  - OBJECTIVES: To investigate the usefulness of matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF MS) typing as a first-line
      epidemiological tool in a nosocomial outbreak of vancomycin-resistant
      Enterococcus faecium (VREfm). METHODS: Fifty-five VREfm isolates, previously
      characterized by whole-genome sequencing (WGS), were included and analysed by
      MALDI-TOF MS. To take peak reproducibility into account, ethanol/formic acid
      extraction and other steps of the protocol were conducted in triplicate. Twenty
      seven spectra were generated per isolate, and spectra were visually inspected to
      determine discriminatory peaks. The presence or absence of these was recorded in
      a peak scheme. RESULTS: Nine discriminatory peaks were identified. A
      characteristic pattern of these could distinguish between the three major WGS
      groups: WGS I, WGS II and WGS III. Only one of 38 isolates belonging to WGS I,
      WGS II or WGS III was misclassified. However, ten of the 17 isolates not
      belonging to WGS I, II or III displayed peak patterns indistinguishable from
      those of the outbreak strain. CONCLUSIONS: Using visual inspection of spectra,
      MALDI-TOF MS typing proved to be useful in differentiating three VREfm outbreak
      clones from each other. However, as non-outbreak isolates could not be reliably
      differentiated from outbreak clones, the practical value of this typing method
      for VREfm outbreak management was limited in our setting.

PMID- 29581055
TI  - Evaluation of the Roche LightMix Gastro parasites multiplex PCR assay detecting
      Giardia duodenalis, Entamoeba histolytica, cryptosporidia, Dientamoeba fragilis,
      and Blastocystis hominis.
AB  - OBJECTIVES: Multiplex PCR assays offer highly sensitive and specific tools for
      the detection of enteric pathogens. This prospective study aimed at comparing the
      novel Roche LightMix Modular Assay Gastro Parasites (LMAGP) detecting Giardia
      duodenalis, Entamoeba histolytica, Cryptosporidium spp., Blastocystis hominis,
      and Dientamoeba fragilis with routine laboratory procedures. METHODS: Stool
      specimens (n = 1062 from 1009 patients) were consecutively examined by LMAGP, R
      Biopharm Ridascreen enzyme immunoassays (EIAs) detecting G. duodenalis or E.
      histolytica/dispar, and microscopy of wet mounts. Discrepant results were
      analysed by in-house PCR. RESULTS: D. fragilis or B. hominis were detected by
      LMAGP in 131 (14.4%) and 179 (19.9%; 16 samples positive by microscopy; p <
      0.0001) of 909 samples, respectively. Of 918 samples analysed for Cryptosporidium
      spp., six were positive by LMAGP (three could be confirmed by Kinyoun staining
      and one by in-house PCR). G. duodenalis was detected by LMAGP, EIA, or microscopy
      in 20, 16, or 9 of 1039 stool samples, respectively; all four samples missed by
      EIA were confirmed by in-house PCR. In total, 938 stool samples were analysed for
      E. histolytica/dispar. Nine of ten EIA-positive samples were negative by LMAGP
      but positive by in-house PCR for E. dispar. One E. histolytica infection
      (positive by both LMAGP and in-house PCR) was missed by EIA and microscopy.
      Parasites only detected by microscopy included Enterobius vermicularis eggs (n =
      3) and apathogenic amoebae (n = 27). CONCLUSIONS: The data call for routine use
      of multiplex PCR assays for the detection of enteric protozoan parasites in
      laboratory diagnostics.

PMID- 29581056
TI  - Development of diagnostic prediction tools for bacteraemia caused by third
      generation cephalosporin-resistant enterobacteria in suspected bacterial
      infections: a nested case-control study.
AB  - OBJECTIVES: Current guidelines for the empirical antibiotic treatment predict the
      presence of third-generation cephalosporin-resistant enterobacterial bacteraemia
      (3GCR-E-Bac) in case of infection only poorly, thereby increasing unnecessary
      carbapenem use. We aimed to develop diagnostic scoring systems which can better
      predict the presence of 3GCR-E-Bac. METHODS: A retrospective nested case-control
      study was performed that included patients >=18 years of age from eight Dutch
      hospitals in whom blood cultures were obtained and intravenous antibiotics were
      initiated. Each patient with 3GCR-E-Bac was matched to four control infection
      episodes within the same hospital, based on blood-culture date and onset location
      (community or hospital). Starting from 32 commonly described clinical risk
      factors at infection onset, selection strategies were used to derive scoring
      systems for the probability of community- and hospital-onset 3GCR-E-Bac. RESULTS:
      3GCR-E-Bac occurred in 90 of 22 506 (0.4%) community-onset infections and in 82
      of 8110 (1.0%) hospital-onset infections, and these cases were matched to 360
      community-onset and 328 hospital-onset control episodes. The derived community
      onset and hospital-onset scoring systems consisted of six and nine predictors,
      respectively. With selected score cut-offs, the models identified 3GCR-E-Bac with
      sensitivity equal to existing guidelines (community-onset: 54.3%; hospital-onset:
      81.5%). However, they reduced the proportion of patients classified as at risk
      for 3GCR-E-Bac (i.e. eligible for empirical carbapenem therapy) with 40% (95%CI
      21-56%) and 49% (95%CI 39-58%) in, respectively, community-onset and hospital
      onset infections. CONCLUSIONS: These prediction scores for 3GCR-E-Bac,
      specifically geared towards the initiation of empirical antibiotic treatment, may
      improve the balance between inappropriate antibiotics and carbapenem overuse.

PMID- 29581057
TI  - Decoding Plant RNA Structurome.

PMID- 29581058
TI  - Nuchal cord at delivery and perinatal outcomes: Single-center retrospective
      study, with emphasis on fetal acid-base balance.
AB  - AIM: Our study objectives were to evaluate umbilical cord blood acid-base balance
      in presence of nuchal cord at delivery, effects of nuchal cord at delivery on
      perinatal outcomes and incidence of nuchal cord in a racially diverse population.
      METHODS: Perinatal records of 2530 women (predominantly African American and
      Hispanic) who delivered in 2012 were examined. Perinatal outcomes of women who
      delivered a baby with nuchal cord were compared with those without nuchal cord.
      RESULTS: In this study, incidence of nuchal cord was 23.5% and incidence of tight
      nuchal cord was 1.9%; 4.2% of babies with nuchal cord required resuscitation and
      3.2% of babies with nuchal cord needed to be admitted to NICU. In our study, 4.2%
      of babies with nuchal cord required resuscitation and in total 3.2% of babies
      with nuchal cord needed to be admitted to NICU. Nuchal cord frequency increased
      from 15.6% at <=36 weeks to 22.8% at >=37 weeks. Significantly elevated umbilical
      cord Veno-Arterial pH differential was noted in babies with nuchal cord,
      indicating fetal acidemia. CONCLUSIONS: Perinatal outcomes of pregnancies with
      nuchal cord in predominantly African American and Hispanic women were not
      adversely affected. Analysis of umbilical cord blood gases suggests mixed
      respiratory and metabolic fetal acidosis.

PMID- 29581059
TI  - Dissociable effects of inter-stimulus interval and presentation duration on rapid
      face categorization.
AB  - Fast periodic visual stimulation combined with electroencephalography (FPVS-EEG)
      has unique sensitivity and objectivity in measuring rapid visual categorization
      processes. It constrains image processing time by presenting stimuli rapidly
      through brief stimulus presentation durations and short inter-stimulus intervals.
      However, the selective impact of these temporal parameters on visual
      categorization is largely unknown. Here, we presented natural images of objects
      at a rate of 10 or 20 per second (10 or 20 Hz), with faces appearing once per
      second (1 Hz), leading to two distinct frequency-tagged EEG responses. Twelve
      observers were tested with three squarewave image presentation conditions: 1)
      with an ISI, a traditional 50% duty cycle at 10 Hz (50-ms stimulus duration
      separated by a 50-ms ISI); 2) removing the ISI and matching the rate, a 100% duty
      cycle at 10 Hz (100-ms duration with 0-ms ISI); 3) removing the ISI and matching
      the stimulus presentation duration, a 100% duty cycle at 20 Hz (50-ms duration
      with 0-ms ISI). The face categorization response was significantly decreased in
      the 20 Hz 100% condition. The conditions at 10 Hz showed similar face
      categorization responses, peaking maximally over the right occipito-temporal
      (ROT) cortex. However, the onset of the 10 Hz 100% response was delayed by about
      20 ms over the ROT region relative to the 10 Hz 50% condition, likely due to
      immediate forward-masking by preceding images. Taken together, these results help
      to interpret how the FPVS-EEG paradigm sets temporal constraints on visual image
      categorization.

PMID- 29581060
TI  - Performance-monitoring integrated reweighting model of perceptual learning.
AB  - Perceptual learning (PL) has been traditionally thought of as highly specific to
      stimulus properties, task and retinotopic position. This view is being
      progressively challenged, with accumulating evidence that learning can generalize
      (transfer) across various parameters under certain conditions. For example,
      retinotopic specificity can be diminished when the proportion of easy to hard
      trials is high, such as when multiple short staircases, instead of a single long
      one, are used during training. To date, there is a paucity of mechanistic
      explanations of what conditions affect transfer of learning. Here we present a
      model based on the popular Integrated Reweighting Theory model of PL but
      departing from its one-layer architecture by including a novel key feature:
      dynamic weighting of retinotopic-location-specific vs location-independent
      representations based on internal performance estimates of these representations.
      This dynamic weighting is closely related to gating in a mixture-of-experts
      architecture. Our dynamic performance-monitoring model (DPMM) unifies a variety
      of psychophysical data on transfer of PL, such as the short-vs-long staircase
      effect, as well as several findings from the double-training literature.
      Furthermore, the DPMM makes testable predictions and ultimately helps understand
      the mechanisms of generalization of PL, with potential applications to vision
      rehabilitation and enhancement.

PMID- 29581061
TI  - Evaluation of some effects on plant metabolism through proteins and enzymes in
      transgenic and non-transgenic soybeans after cultivation with silver
      nanoparticles.
AB  - : To evaluate the effects of silver nanoparticles (AgNP) exposition, transgenic
      (through gene cp4EPSPS) and non-isogenic non-transgenic soybeans were cultivated
      in the presence or absence of AgNP or silver nitrate (AgNO3) at 50 mg/kg of
      silver. Physiological aspects of the plants including mass production and
      development of roots, proteomics such as protein amount and differential
      proteins, enzymes and lipid peroxidation were determined after exposition. The
      mass production of non-transgenic plants treated with AgNP or AgNO3 was decreased
      by 25 and 19%, respectively, on their mass based, while for transgenic soybean
      this effect was observed for AgNP cultivation only. Fifty-nine proteins were
      identified from the differentially abundant spots by two-dimensional difference
      gel electrophoresis and nano-electrospray ionization liquid chromatography
      coupled tandem mass spectrometry. Identified species as ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO), ATP synthase, superoxide dismutase (SOD),
      related to plant metabolism were less abundant for the cultivation with either
      AgNP and AgNO3 than the control. Finally, this work demonstrated significant
      correlation as evidenced by changes in lipid peroxidation content and catalase
      activity, which were a result of exposure to either AgNP or AgNO3 cultivations.
      Further, necrotic areas in the basal part of the stems and damage or chlorotic
      areas were found in the leaves. SIGNIFICANCE: Once nanoparticles have been
      employed for several applications in recent years and they can be released in the
      environmental matrices, this study highlights proteomic and enzymatic alterations
      in transgenic and non-transgenic soybeans, an important crop, after cultivation
      with silver nanoparticles. Such strategy employing proteomic and enzymatic
      approaches to evaluate soybeans exposed to silver nanoparticles has not yet been
      reported. Therefore, the results obtained in this study can expand the
      information concerning the effects of silver nanoparticles in soybean plants.

PMID- 29581062
TI  - Editorial: A matter of ingredients.

PMID- 29581063
TI  - Characterization of rat primary trigeminal satellite glial cells and associated
      extracellular vesicles under normal and inflammatory conditions.
AB  - Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of
      chronic pain, potentially through mediating extracellular or paracrine signaling.
      Recently, extracellular vesicles (EVs) in the form of exosomes have been found to
      play an important role in cell-cell communication. However, their release from
      SGCs and extent in modulating pain remain unknown. An in vitro cell platform
      using fresh primary SGCs was used to characterize the shed vesicles by size and
      proteomic profiling following activation of SGCs by lipopolysaccharide (LPS),
      simulating neurogenic inflammation in vivo. Results demonstrated that SGCs shed
      vesicles in the size range of exosomes (>150 nm) but with altered protein
      expression upon LPS-activation. Proteomic profiling of SGCs-shed EVs showed that
      a number of proteins were differentially regulated upon LPS stimulation such as
      junction plakoglobin and myosin 9 that are proposed as novel biomarkers of SGCs
      activation under inflammatory conditions. Findings from this study highlight the
      utility of using fresh primary SGC cultures as a model to further investigate EVs
      under normal and inflammatory conditions. SIGNIFICANCE: This study demonstrated
      that.

PMID- 29581064
TI  - Molecular signatures of medullary thyroid carcinoma by matrix-assisted laser
      desorption/ionisation mass spectrometry imaging.
AB  - : The main aim of the study was to assess the feasibility of matrix-assisted
      laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in the
      pathological investigation of Medullary Thyroid Carcinoma (MTC). Formalin-fixed
      paraffin-embedded (FFPE) samples from seven MTC patients were analysed by MALDI
      MSI in order to detect proteomic alterations within tumour lesions and to define
      the molecular profiles of specific findings, such as amyloid deposition and C
      cell hyperplasia (CCH). nLC-ESI MS/MS was employed for the identification of
      amyloid components and to select alternative proteomic markers of MTC
      pathogenesis. Results highlighted the potential of MALDI-MSI to confirm the
      classic immunohistochemical methods employed for the diagnosis of MTC, with good
      sensitivity and specificity. Intratumoural amyloid components were also detected
      and identified, and were characterised by calcitonin, apolipoprotein E,
      apolipoprotein IV, and vitronectin. The tryptic peptide profiles representative
      of MTC and CCH were distinctly different, with four alternative markers for MTC
      being detected; K1C18, and three histones (H2A, H3C, and H4). Finally, a further
      115 proteins were identified through the nLC-ESI-MS/MS analysis alone, with
      moesin, veriscan, and lumican being selected due to their potential involvement
      in MTC pathogenesis. This approach represents a complimentary strategy that could
      be employed to detect new proteomic markers of MTC. STATEMENT OF SIGNIFICANCE:
      Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that originates
      from the parafollicular C-cells of the thyroid. The diagnosis is typically
      established using a combination of fine-needle aspiration biopsy (FNAB) of a
      suspicious nodule along with the demonstrable elevation of serum biomarkers, such
      as calcitonin and carcinoembryonic antigen (CEA). Unfortunately, this combination
      is often associated with a high degree of false-positive results and this can
      lead to misdiagnosis and avoidable total thyroidectomy. The current study
      presents the potential role of MALDI-MSI in the search for new proteomic markers
      of MTC with diagnostic and prognostic significance. MALDI-MSI was capable of
      detecting the classic immunohistochemical markers employed for the diagnosis of
      MTC, with good sensitivity and specificity. Furthermore, the complementary
      combination of MALDI-MSI and nLC-ESI-MS/MS analysis, using a single tissue
      section, enabled further potential markers to be identified and their spatial
      localisation visualised within tumoural regions. Such findings could be a
      valuable starting point for further studies focused on confirming the data
      presented here using thyroid FNABs, with the final objective being to provide
      complimentary assistance for the detection of MTC during the pre-operative phase.

PMID- 29581066
TI  - No lower bacterial adhesion for ceramics compared to other biomaterials: An in
      vitro analysis.
AB  - BACKGROUND: Although there is some clinical evidence of ceramic bearings being
      associated with a lower infection rate after total hip arthroplasty (THA),
      available data remains controversial since this surface is usually reserved for
      young, healthy patients. Therefore, we investigated the influence of five
      commonly used biomaterials on the adhesion potential of four biofilm-producing
      bacteria usually detected in infected THAs. HYPOTHESIS: Ceramic biomaterials
      exhibit less bacterial adherence than other biomaterials. MATERIAL AND METHODS:
      In this in vitro research, we evaluated the ability of Staphylococcus aureus,
      Staphylococcus epidermidis ATCC 35984, Escherichia coli ATCC 25922 and
      Pseudomonas aeruginosa to adhere to the surface of a cobalt-chromium metal head,
      a fourth-generation ceramic head, a fourth-generation ceramic insert, a highly
      crossed linked polyethylene insert and a titanium porous-coated acetabular
      component. After an initial washing step, bacterial separation from the surface
      of each specimen was done with a vortex agitator. The colony-forming units were
      counted to determine the number of viable adherent bacteria. RESULTS: We found no
      differences on global bacterial adhesion between the different surfaces (p=0.5).
      E. coli presented the least adherence potential among the analysed pathogens
      (p<0.001). The combination of E. coli and S. epidermidis generated an antagonist
      effect over the adherence potential of S. epidermidis individually (58+/-4% vs.
      48+/-5%; p=0.007). The combination of P. aeruginosa and S. aureus presented a
      trend to an increased adherence of P. aeruginosa independently, suggesting an
      agonist effect (71% vs. 62%; p=0.07). DISCUSSION: Ceramic bearings appeared not
      to be related to a lower bacterial adhesion than other biomaterials. However,
      different adhesive potentials among bacteria may play a major role on infection's
      inception. LEVEL OF EVIDENCE: IV, in vitro study.

PMID- 29581065
TI  - Micelle directed chemical polymerization of polypyrrole particles for the
      electrically triggered release of dexamethasone base and dexamethasone phosphate.
AB  - Conducting polymers such as polypyrrole (PPy) can be used as electrically
      responsive drug delivery systems typically prepared by electrochemical
      polymerisation, however, the amount of drug that can be delivered is typically
      low. To increase drug delivery capacity and prepare larger amounts of polymer,
      PPy nanoparticles were produced by chemical polymerisation over drug-loaded
      micelles. Two forms of dexamethasone were included to increase total drug loading
      and to explore the mechanisms of loading and release. The particles produced were
      approximately 50 nm in size and their conductivity and reversible redox activity
      were demonstrated. Loading of the hydrophobic dexamethasone base was more
      efficient than for the more hydrophilic phosphate salt. After pressing the
      particles into the desired form, electrically-responsive drug release was
      achieved with a pulsed potential signal being the most effective way to trigger
      release. Notably, the anionic phosphate salt of the drug was more sensitive to
      electrically stimulated release than the uncharged base of dexamethasone,
      highlighting the role of electrostatic forces in driving drug release. This
      system has potential to be loaded with different drugs widening the scope of
      application of these smart particles to treat a range of disease states.

PMID- 29581067
TI  - The use of the LARS system in the treatment of AC joint instability - Long-term
      results after a mean of 7.4 years.
AB  - BACKGROUND: The acromioclavicular (AC) joint is of great importance for shoulder
      stability and one of the most frequently injured regions of the shoulder.
      HYPOTHESIS: AC joint reconstruction with the ligament augmentation &
      reconstruction system (LARSTM) leads to a good-to-excellent outcome at long-term
      follow-up. PATIENTS AND METHODS: This study was performed as a retrospective
      single-centre data analysis of a level-I trauma centre. All patients treated
      operatively for an acute AC dislocation with the LARSTM between 2003 and 2013
      were included. RESULTS: The study group consisted of three female (6%) and 44
      male patients (94%) with an average age of 37 years and a minimum follow-up of
      two years. The overall mean clinical outcomes at latest follow-up were: Constant
      93, DASH 2.64, ASES 96, SST 97, UCLA 34 and VAS 0.4-representing a good-to
      excellent outcome in all patients. Overall, 45 patients (96%) reported to be very
      satisfied with the achieved result at latest follow-up. In five patients, (11%)
      complications occurred during the follow-up period, requiring surgical revision
      in four of the five patients (80%). CONCLUSION: AC joint reconstruction with the
      LARSTM achieves good-to-excellent clinical and functional outcomes at long-term
      follow-up with a surgical revision rate of 8.5%. LEVEL OF EVIDENCE: Retrospective
      follow-up study, case series, level IV.

PMID- 29581068
TI  - Total hip arthroplasty after a previous pelvic osteotomy: A systematic review and
      meta-analysis.
AB  - BACKGROUND: There are several reports regarding total hip arthroplasty (THA)
      after a previous pelvic osteotomy (PO). However, to our knowledge, until now
      there has been no formal systematic review and meta-analysis published to
      summarize the clinical results of THA after a previous PO. Therefore, we
      conducted a systematic review and meta-analysis of results of THA after a
      previous PO. We focus on these questions as follows: does a previous PO affect
      the results of subsequent THA, such as clinical outcomes, operative time,
      operative blood loss, and radiological parameters. METHODS: Using PubMed, Web of
      Science, and Cochrane Library, we searched for relevant original papers. The
      pooling of data was performed using RevMan software (version 5.3, Cochrane
      Collaboration, Oxford, UK). A p-value<0.05 was judged as significant.
      Standardized mean differences (SMD) were calculated for continuous data with a
      95% confidence interval (CI) was reported. Statistical heterogeneity was assessed
      based on I2 using standard chi2 test. When I2>50%, significant heterogeneity was
      assumed and a random-effects model was applied for the meta-analysis. A fixed
      effects model was applied in the absence of significant heterogeneity. RESULTS:
      Eleven studies were included in this meta-analysis. The pooled results indicated
      that there was no significant difference in postoperative Merle D'Aubigne-Postel
      score (I2=0%, SMD=-0.15, 95% CI: -0.36 to 0.06, p=0.17), postoperative Harris hip
      score (I2=60%, SMD=-0.23, 95% CI: -0.50 to 0.05, p=0.10), operative time (I2=86%,
      SMD=0.37, 95% CI: -0.09 to 0.82, p=0.11), operative blood loss (I2=82%, SMD=0.23,
      95% CI: -0.17 to 0.63, p=0.25), and cup abduction angle (I2=43%, SMD=-0.08, 95%
      CI: -0.25 to 0.09, p=0.38) between THA with and without a previous PO. However,
      cup anteversion angle of THA with a previous PO was significantly smaller than
      that of without a previous PO (I2=77%, SMD=-0.63, 95% CI: -1.13 to -0.13,
      p=0.01). CONCLUSION: Systematic review and meta-analysis of results of THA after
      a previous PO was performed. A previous PO did not affect the results of
      subsequent THA, except for cup anteversion. Because of the low quality evidence
      currently available, high-quality randomized controlled trials are required.
      LEVEL OF EVIDENCE: Level III, meta-analysis of case-control studies.

PMID- 29581069
TI  - Capitellar erosion after radial head arthroplasty: A comparative biomechanical
      study of operated radial head fractures on cadaveric specimens.
AB  - BACKGROUND: We asked whether open reduction and internal fixation (ORIF) or
      radial head arthroplasty (RHA), common techniques used for the confrontation of
      displaced or comminuted radial head fractures, are correlated with cartilage wear
      of the capitulum. HYPOTHESIS: We hypothesized that neither ORIF nor RHA are
      correlated with capitellar cartilage wear. MATERIAL AND METHODS: On 5 cadaveric
      elbow specimens, osteotomies were employed to simulate radial head comminuted
      fractures followed with ORIF by Herbert screws. Radial heads were also excised
      from other 5 cadaveric elbow specimens and were replaced by metallic monopolar
      implants. Finally, 2 elbows were not operated and used as a control group. Custom
      made rotary machines, working unstoppably, generated 700,000 pronation and
      supination forearm movements at a 110 degrees  arc of motion. The elbow joints
      were examined with pre- and postoperative magnetic resonance imaging (MRI) scans
      and the articular surfaces of the capitula were resected and sent for
      histopathology study. RESULTS: In the 2 cadaveric elbows of the control group and
      the 4 elbows treated with ORIF, no cartilage damage was found. The fifth one
      displayed cartilage fissures, which were, classified according to International
      Cartilage Repair Society (ICRS) grading system as grade I cartilage damage. On
      the contrary, all 5 elbows treated with RHA sustained complete cartilage loss,
      exposure of the subchondral bone and were classified as ICRS grade IV cartilage
      damage. DISCUSSION: Our study suggests that metallic monopolar RHA after a
      displaced or comminuted radial head fracture carries a high risk of rapidly
      evolving cartilage loss of the capitulum.

PMID- 29581070
TI  - Diagnostic accuracy of the alpha defensin lateral flow device (Synovasure) for
      periprosthetic infections in microbiologically complex situations: A study of 42
      cases in a French referral centre.
AB  - BACKGROUND: Joint aspiration is currently the reference standard test for
      diagnosing periprosthetic joint infection (PJI) despite the high rate of false
      negative results, of which a major cause is the fastidious nature of some
      microorganisms. A rapid diagnostic test that detects alpha defensin
      (SynovasureTM, Zimmer, Warsaw, IN, USA) in joint fluid can provide the diagnosis
      of PJI within a few minutes across the full spectrum of causative organisms
      (including mycobacteria and yeasts). Its performance in detecting bacterial
      infections is unaltered by concomitant antibiotic therapy. Few studies of
      SynovasureTM have been conducted by groups that were involved in designing the
      test, which has not been validated in France. Assessments in referral centres
      where complex microbiological situations are common hold considerable interest.
      The objective of this prospective study was to determine the sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and causes of error of SynovasureTM used to diagnose periprosthetic infection in
      complex microbiological situations. HYPOTHESIS: The rapid diagnostic test
      SynovasureTM has greater than 90% NPV for detecting periprosthetic infections in
      complex microbiological infections. MATERIAL AND METHODS: SynovasureTM was used
      42 times in 39 patients between October 2015 and October 2017 in challenging
      microbiological situations [discordant joint aspiration results (n=20), negative
      cultures with clinical or laboratory evidence of infection, (n=21), and
      concomitant antibiotic therapy (n=1)]. Of the 39 patients, 23 had total knee
      prostheses, 13 total hip prostheses, and 3 total femoral prostheses. The
      reference standard to which the SynovasureTM results were compared was the PJI
      criteria set developed by the Musculoskeletal Infection Society (MSIS). RESULTS:
      SynovasureTM was negative in 30 cases with negative joint fluid cultures (30/42,
      71.4%). Of the 12 (28.6%) cases with positive SynovasureTM results, only 7 (7/12,
      58.3%) had positive joint fluid cultures. According to the MSIS criteria 9 cases
      were infected, including 8 with positive and 1 with negative SynovasureTM
      results. Of the 33 cases that were not infected according to MSIS criteria, 29
      had negative and 3 positive SynovasureTM results; the remaining case had a
      positive SynovasureTM result but was excluded when metallosis was found intra
      operatively. NPV was 96.7%, PPV 72.7%, sensitivity 88.9%, and specificity 90.6%.
      DISCUSSION: The high NPV of SynovasureTM suggests a role for this test in
      microbiologically complex situations as a new tool for ruling in and, most
      importantly, ruling out infection in doubtful cases. LEVEL OF EVIDENCE: III,
      prospective study of diagnostic accuracy.

PMID- 29581071
TI  - A comparison of complication rates between locking and non-locking plates in
      distal fibular fractures.
AB  - BACKGROUND: Locking compression plates have become increasingly popular in
      orthopaedic surgery. However, the gold standard of treatment for distal fibular
      fractures remains fixation with a non-locking one-third tubular plate. It has
      been reported that locking plates in distal fibular fractures are associated with
      an increased complication rate. HYPOTHESIS: The objective of this study is to
      assess the complication rates of locking versus non-locking plates in patients
      who underwent surgical fixation of distal fibular fractures. MATERIALS & METHODS:
      A retrospective analysis of closed distal fibular fractures that underwent
      surgical repair over a 2-year period with either a locking or non-locking plate
      was undertaken, analysing the groups for both wound and overall postoperative
      complications. RESULTS: A total of 160 patients were treated over 2 years, of
      which 129 and 31 patients were treated with non-locking and locking plates
      respectively. There was no significant difference between the non-locking and
      locking plates overall complication rates (13.5% versus 15.4%, p=0.76) or wound
      complication rates (3.97% versus 3.85%, p=1.00). DISCUSSION: Distal fibular
      fractures managed with locking plates do not have a higher complication rate in
      comparison to those managed with non-locking plates. LEVEL OF EVIDENCE: III (case
      control study).

PMID- 29581072
TI  - Morcellation during Uterine Tissue Extraction: An Update.

PMID- 29581073
TI  - Association of Endometriosis and Adenomyosis: Vast Literature but Scant
      Conclusive Data.

PMID- 29581074
TI  - Antimicrobial susceptibility profiles of bacteria causing urinary tract
      infections in Mexico: Single-centre experience with 10 years of results.
AB  - OBJECTIVES: The aim of this retrospective study was to describe urinary tract
      infections (UTIs) diagnosed in a single centre in Mexico through 10 years of
      results, with a particular emphasis on the aetiology, patterns of antimicrobial
      susceptibility and incidence of extended-spectrum beta-lactamase (ESBL)-producing
      strains. METHODS: This study involved all urine samples analysed during the
      period March 2007 to September 2017 in a single centre in Mexico. Isolated
      uropathogens were identified to species level using routine laboratory methods,
      and antimicrobial susceptibility was determined by the disk diffusion method.
      RESULTS: Overall, 859 urinary isolates were identified, including 582 (67.8%)
      Escherichia coli, 69 (8.0%) Enterococcus faecalis, 29 (3.4%) Klebsiella
      pneumoniae, 24 (2.8%) Proteus mirabilis, 24 (2.8%) Pseudomonas aeruginosa, 23
      (2.7%) Candida albicans, 18 (2.1%) Streptococcus agalactiae and 10 (1.2%) Candida
      glabrata. Patient sex and age were the main risk factors associated with UTI in
      this population. Nitrofurantoin together with fosfomycin and amikacin had the
      highest percentages of susceptibility. Of the 859 isolates, 213 (24.8%) presented
      a positive double-disk synergy test indicating the presence of an ESBL phenotype,
      with E. coli showing a gradual increase in ESBL-producing isolates over time.
      CONCLUSIONS: These results provide additional evidence in relation to the role of
      different bacterial species as aetiological agents of UTI as well as
      antimicrobial susceptibility information that will help to guide the selection of
      antimicrobial treatment for UTIs and the prevalence of ESBL-producing strains
      over a 10-year period in a Mexican centre.

PMID- 29581076
TI  - Helicobacter pylori therapy and clinical perspective.
AB  - Helicobacter pylori induces chronic gastritis and duodenal ulcer in a small
      fraction of the colonised population. Three decades after the discovery of H.
      pylori and disclosure of an urgent need for eliminating the bacterium in
      patients, it seems that we are still in the first steps of dealing with this
      mysterious organism. Treatment of H. pylori is a complex dilemma for clinicians,
      a repeating sentence by many scientists who spend years on this research topic.
      Apart from many modifications in initial first-line treatment of H. pylori,
      gastroenterologists are unable to overcome the problem of therapeutic failure.
      Choosing the best regimen in any region depends on many factors, which have been
      the focus of many randomised clinical trials. A potential increase in efficacy of
      future therapies may be influenced by adding the novel potassium-competitive acid
      blocker vonoprazan. Undeniably, in-depth analysis is necessary to propose more
      effective therapeutic regimens. Meanwhile, we recommend the performance of
      antimicrobial susceptibility testing before any antimicrobial prescription.

PMID- 29581075
TI  - Distribution of extended-spectrum beta-lactam, quinolone and carbapenem
      resistance genes, and genetic diversity among uropathogenic Escherichia coli
      isolates in Tehran, Iran.
AB  - OBJECTIVES: Antimicrobial resistance among uropathogenic Escherichia coli (UPEC)
      is increasing. The aim of this study was to evaluate antimicrobial resistance in
      UPEC isolates and its correlation with virulence factors. METHODS: A total of 120
      E. coli isolates were collected from patients with urinary tract infection in
      Tehran, Iran. Biofilm formation and antimicrobial susceptibility were determined
      by phenotypic tests. The combination disk diffusion test and modified Hodge test
      (MHT) were performed for phenotypic detection of extended-spectrum beta
      lactamases (ESBLs) and carbapenemases, respectively. PCR was used for the
      detection of virulence genes, ESBL-encoding genes, and quinolone (qnr) and
      carbapenem resistance genes. Pulsed-field gel electrophoresis (PFGE) was
      performed to explore the genetic relatedness among isolates. RESULTS: Most
      isolates exhibited biofilm formation, and different frequencies of virulence
      genes were observed. There was a high rate of resistance, especially multidrug
      resistance, to most of the antimicrobial agents tested. Phenotypically, 67.5% of
      the isolates produced an ESBL and were resistant to different antimicrobial
      classes. In total, 83.3% of the isolates harboured ESBL genes, especially blaTEM
      and blaCTX-M, and 32.5% were positive for the quinolone resistance genes qnrS and
      qnrB. All isolates were negative for carbapenemases by the MHT and PCR. These
      results indicate the association between the presence of various virulence genes
      and antimicrobial susceptibility. PFGE analysis showed that there was great
      clonal diversity among the selected isolates, with 17 isolates divided into five
      clusters. CONCLUSIONS: These results indicate that the high antimicrobial
      resistance among UPEC isolates is alarming and requires urgent attention.

PMID- 29581077
TI  - Acute Disseminated Encephalomyelitis After Herpes Simplex Virus
      Meningoencephalitis in Adult.

PMID- 29581078
TI  - Alogliptin in Patients with Type 2 Diabetes Receiving Metformin and Sulfonylurea
      Therapies in the EXAMINE Trial.
AB  - BACKGROUND: We evaluated the antihyperglycemic efficacy and safety of adding the
      dipeptidyl dipeptidase-4 inhibitor alogliptin to metformin and sulphonylurea in
      the treatment of type 2 diabetes in the Examination of Cardiovascular Outcomes
      with Alogliptin versus Standard of Care Trial. METHODS: Patients with type 2
      diabetes and recent acute coronary syndrome were randomized to alogliptin or
      placebo and standard of care. Participants were followed for up to 40 (median 18)
      months. In a subgroup taking metformin and sulphonylurea at baseline, we
      evaluated change from baseline in glycated hemoglobin (HbA1c), adverse events,
      cardiovascular outcomes, laboratory data, and other safety parameters. RESULTS:
      There were 1398 patients receiving baseline dual therapy (metformin and
      sulphonylurea only) randomized to alogliptin (N = 693) or placebo (N = 705); 550
      patients receiving alogliptin and 505 patients receiving placebo completed the
      Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care
      without addition of other antihyperglycemic therapies (P = .008). Changes from
      baseline to last visit in HbA1c were -0.4% on alogliptin and +0.1% on placebo (P
      < .001) in all those with baseline dual therapy and -0.4% for alogliptin and
      +0.2% for placebo (P < .001) in those without additional therapies. Reported
      rates of hypoglycemia were 8.8% for alogliptin and 6.7% for placebo (P = .16).
      Cardiovascular death and all-cause mortality rates were lower in those receiving
      alogliptin compared with those receiving placebo (hazard ratio, 0.49; 95%
      confidence interval, 0.28-0.84 and hazard ratio, 0.61; 95% confidence interval,
      0.38-0.96, respectively). CONCLUSIONS: Addition of the dipeptidyl peptidase-4
      inhibitor alogliptin to dual therapy with metformin plus sulfonylurea
      significantly reduced HbA1c and was well tolerated. Lower mortality rates were
      seen in patients treated with alogliptin in this subgroup.

PMID- 29581079
TI  - Thiazolidinediones and Risk of Atrial Fibrillation Among Patients with Diabetes
      and Coronary Disease.
AB  - BACKGROUND: We sought to determine whether insulin-sensitizing therapy
      (thiazolidinediones or metformin) decreased the risk of developing atrial
      fibrillation compared with insulin-providing therapy (insulin, sulfonylurea, or a
      meglitinide). Thiazolidinediones are insulin sensitizers that also decrease the
      inflammatory response. Because inflammation is a risk factor for atrial
      fibrillation, we hypothesized that treating diabetes with thiazolidinediones
      might decrease the risk of developing atrial fibrillation. METHODS: The Bypass
      Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial enrolled
      patients with type 2 diabetes and documented coronary artery disease. All
      patients were randomized to insulin-sensitizing therapy or insulin-providing
      therapy. RESULTS: A total of 2319 patients entered the study, with 1160 assigned
      to the insulin-sensitization strategy and 1159 assigned to the insulin-provision
      strategy. Over a median follow-up of 4.2 years, 90 patients (3.9%) developed new
      onset atrial fibrillation. In the intention-to-treat analysis, the incidence of
      atrial fibrillation was 8.7 per 1000 person-years in patients assigned to insulin
      sensitization compared with 9.5 in patients assigned to insulin provision with a
      hazard ratio (HR) of 0.91 (95% confidence interval [CI], 0.60-1.38, P = .66). In
      a time-varying exposure analysis, the incidence rate per 1000 person-years was
      7.2 while exposed to thiazolidinediones and 9.7 while not exposed to
      thiazolidinediones with an adjusted HR of 0.80 (95% CI, 0.33-1.94, P = .62). In a
      subset of patients matched on propensity to receive a thiazolidinediones, the HR
      was 0.75 (95% CI, 0.43-1.30, P = .30). CONCLUSIONS: We did not find a significant
      reduction of atrial fibrillation incidence with use of thiazolidinediones.

PMID- 29581080
TI  - Persistent Profound Lactic Acidosis: an Unusual Case.

PMID- 29581081
TI  - Silencing SOCS1 in dendritic cells promote survival of mice with systemic Candida
      albicans infection via inducing Th1-cell differentiation.
AB  - Enhancing the immunity conferred by dendritic cells (DCs) to fungal infection
      represents a promising strategy in the number of immunocompromised individuals.
      In a previous study, we demonstrated that suppressor of cytokine signaling 1
      (SOCS1) silencing can promote the maturation of DCs and induce an immune response
      against Candida albicans (C. albicans) in vitro. Herein, the effectiveness of
      SOCS1 suppression administered by SOCS1-siRNA-treated DCs is further evaluated in
      systemic candidiasis mouse model. The SOCS1-silenced DCs increase mouse survival
      and significantly decrease fungal colonization in the kidneys. We confirm that
      the serum IFN-gamma levels in SOCS1-siRNA-treated mice are higher than in all
      other infected groups at the early stages of infection, which correlates with a
      higher differentiation of IFN-gamma+CD4+ T cells (Th1) in the spleen. Meanwhile,
      the differentiation of IL-4-producing CD4+ T (Th2) or IL-17-producing CD4+ T
      cells (Th17 cells) remain unaffected under the same treatment, suggesting that
      SOCS1-silenced DCs significantly affect the IFN-gamma-producing CD4+ T cells
      (Th1). However, at the late stages of infection when the differentiation of Th1,
      Th2 and Th17 cells decreases in SOCS1-silenced-DCs-treated mice, all the serum
      cytokines (IFN-gamma, IL-4 and IL-17) are also reduced. In summary, treatment of
      mice with SOCS1-silenced DCs can protect mice from systemic infection during the
      early stages and thereby increase overall survival. We conclude that the increase
      in Th1 response in early stages avoids the cascade inflammatory response in later
      stages that is known to place such a large fungal load on the kidneys and cause
      subsequent death.

PMID- 29581083
TI  - Long-term predictors for psychological outcome of pre-symptomatic testing for
      late-onset neurological diseases.
AB  - This longitudinal study aimed at determining predicting variables for middle and
      long-term psychological disturbance due pre-symptomatic testing (PST) for two
      late-onset neurological diseases, Huntington disease (HD) and TTR (transthyretin
      protein) familial amyloid polyneuropathy (FAP) Val30Met (now classified as
      Val50Met). 196 clinical records of persons who performed PST at least three years
      ago and answered to the two stages of evaluation (before PST and least 3 years
      after disclosure of results) were analysed. For this purpose, regression analysis
      was performed, showing that the Positive Symptom Distress Index (PSDI),
      psychoticism, somatization and paranoid ideation dimensions assume predictive
      value in the middle and long-term impact for total anxiety and PSDI. The result
      of PST was not a relevant predictor. The application of an evaluation instrument
      of various psychopathological dimensions played a fundamental role in the
      detection of clinical situations that may arise several years later after PST.
      Attention should be paid to providing psychological support to persons at-risk
      who, at the pre-test phase, present some psychopathology indices before pursuing
      with genetic testing.

PMID- 29581082
TI  - Methylmercury alters proliferation, migration, and antioxidant capacity in human
      HTR8/SV-neo trophoblast cells.
AB  - Methylmercury, a potent neurotoxin, is able to pass through the placenta, but its
      effects on the placenta itself have not been elucidated. Using an immortalized
      human trophoblast cell line, HTR8/SV-neo, we assessed the in vitro toxicity of
      methylmercury. We found that 1 MUg/mL methylmercury decreased viability,
      proliferation, and migration; and it had effects on antioxidant genes similar to
      those seen in neural cells. However, methylmercury led to decreased expression of
      superoxide dismutase 1 and increased expression of surfactant protein D. HTR
      cells treated 0.01 or 0.1 MUg/mL methylmercury had increased migration rates
      along with decreased expression of an adhesion gene, cadherin 3, suggesting that
      low doses of methylmercury promote migration in HTR cells. Our results indicate
      that trophoblast cells react differently to methylmercury relative to neural cell
      lines, and thus investigation of methylmercury toxicity in placental cells is
      needed to understand the effects of this heavy metal on the placenta.

PMID- 29581084
TI  - Beyond the five-year horizon: long-term outcome of high-risk and inoperable
      patients undergoing TAVR with first-generation devices.
AB  - AIMS: We sought to determine the long-term outcome of high-risk patients who
      underwent transcatheter aortic valve replacement (TAVR) with first-generation
      devices with a focus on the identification of predictors for mortality and valve
      durability. METHODS AND RESULTS: Consecutive patients in our prospective single
      centre registry undergoing TAVR with first-generation devices (n=214 CoreValve;
      n=86 SAPIEN) between 06/2007 and 07/2009 were retrospectively analysed (n=300,
      mean age 81.43+/-6.55 years, mean STS score 6.5+/-4.5%). Kaplan-Meier estimates
      of survival and the Cox proportional hazards model were used to identify
      independent predictors of all-cause-mortality. At 1, 5, and 7 years, estimated
      survival rates were 76.0%, 40.2%, and 23.2%, respectively. Age-adjusted baseline
      predictors of mortality included atrial fibrillation, impaired kidney function,
      peripheral artery disease, and mitral regurgitation (>=moderate). Baseline risk
      adjusted procedure-related predictors for all-cause mortality included acute
      kidney injury, neurological events, major vascular complications, and major/life
      threatening bleeding. At both five and six years, 78.2% of surviving patients
      were in NYHA Class I or II. PVL was <=mild in the majority of patients at
      discharge and throughout follow-up. At seven years, the overall crude cumulative
      incidence of structural valve deterioration according to the 2017 EAPCI/ESC/EACTS
      definition was 14.9% (CoreValve 11.8% vs. SAPIEN 22.6%; p=0.01). CONCLUSIONS:
      Seven years after TAVR, 23.2% of high-risk patients were still alive. Independent
      predictors of all-cause mortality included both patient- and procedure-related
      factors. With a cumulative incidence of 14.9% at seven years, there is some
      suggestion that SVD post TAVR may become increasingly relevant during longer-term
      follow-up.

PMID- 29581085
TI  - Qualitative Resting Coronary Pressure Wave Form Analysis to Predict Fractional
      Flow Reserve.
AB  - AIMS: To evaluate the predictability of resting distal coronary pressure wave
      forms for fractional flow reserve (FFR). METHODS AND RESULTS: Resting coronary
      wave forms were qualitatively evaluated for the presence of (i) dicrotic notch;
      (ii) diastolic dipping; and (iii) ventricularization. In a development cohort
      (n=88) a scoring system was developed that was then applied to a validation
      cohort (n=428) using a multivariable linear regression model to predict FFR and
      receiver operating characteristics (ROC) to predict FFR <=0.8. In the development
      cohort, all 3 qualitative parameters were independent predictors of FFR. However,
      in a multivariable linear regression model in the validation cohort, qualitative
      wave form analysis did not further improve the ability of resting distal coronary
      to aortic pressure ratio (Pd/Pa) (p=0.80) or instantaneous wave-free ratio (iFR)
      (p=0.26) to predict FFR. Using ROC, the area under the curve of resting Pd/Pa
      (0.86 versus 0.86, P=0.08) and iFR (0.86 versus 0.86, P=0.26) did not improve by
      adding qualitative analysis. CONCLUSIONS: Qualitative coronary wave form analysis
      showed moderate classification agreement in predicting FFR but did not add
      substantially to the resting pressure gradients Pd/Pa and iFR; however, when
      discrepancies between quantitative and qualitative analyses are observed,
      artifact or pressure drift should be considered.

PMID- 29581086
TI  - Acute performance of first- and second-generation transcatheter aortic valves: a
      quantitative videodensitometric assessment of aortic regurgitation.

PMID- 29581087
TI  - Improving Health-Related Quality of Life of Patients With an Ostomy Using a Novel
      Digital Wearable Device: Protocol for a Pilot Study.
AB  - BACKGROUND: Ostomy surgeries involving the placement of an ostomy bag (eg,
      colostomy, ileostomy, urostomy, etc) have been shown to have a negative impact on
      health-related quality of life. To date, no studies have been conducted examining
      what impact, if any, wearable biosensors have on the health-related quality of
      life of ostomy patients. OBJECTIVE: In the present study, we plan to assess the
      quality of life of ostomy patients using the Ostom-i alert sensor, a portable,
      wearable, Bluetooth-linked biosensor that facilitates easier ostomy bag output
      measurements. We hypothesize that using the Ostom-i alert sensor will result in
      an improved, ostomy-specific, health-related quality of life as compared to
      baseline measurement before the use of the sensor. METHODS: A total of 20 ostomy
      patients will be screened and recruited to participate in this prospective,
      observational, cross-over pilot study using an Ostom-i alert sensor for one
      month. The primary outcome of this study will compare ostomy-specific, health
      related quality of life at baseline (prior to Ostom-i alert sensor use) to ostomy
      specific, health-related quality of life after 2 and 4 weeks of Ostom-i use by
      utilizing the City of Hope Quality of Life Questionnaire for Patients with an
      Ostomy. Secondary outcomes of general health-related quality of life and
      adjustment to ostomy will be evaluated using the Medical Outcomes Study 36-item
      short form health survey and the Olbrisch Ostomy Adjustment Scale Short Form 2.
      RESULTS: The project was funded by the Department of Anesthesiology,
      Perioperative and Pain Medicine at Stanford University School of Medicine.
      Enrollment is currently underway and data analysis is expected to be completed in
      2018. CONCLUSIONS: Proposed benefits of mobile, internet-linked personal health
      monitors, such as the Ostom-i, include a reduction in the cost of care by
      reducing resource utilization and infection rates, improving patient-provider
      communication, reducing time spent as an inpatient as well as improved quality of
      life. Prior studies have demonstrated decreased health-related quality of life in
      patients with an ostomy bag. We aim to examine the extent to which the Ostom-i
      alert sensor affects the health-related quality of life of its users. The Ostom-i
      alert sensor has the potential to improve quality of life of users by giving them
      the freedom and confidence to partake in daily activities with the knowledge that
      they can check how full their ostomy bag is in a private, discrete manner. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02319434;
      https://clinicaltrials.gov/ct2/show/NCT02319434 (Archived at WebCite at
      http://www.webcitation.org/6xhFDThmq).

PMID- 29581088
TI  - Effect of Harm Anchors in Visual Displays of Test Results on Patient Perceptions
      of Urgency About Near-Normal Values: Experimental Study.
AB  - BACKGROUND: Patient-facing displays of laboratory test results typically provide
      patients with one reference point (the "standard range"). OBJECTIVE: To test the
      effect of including an additional harm anchor reference point in visual displays
      of laboratory test results, which indicates how far outside of the standard range
      values would need to be in order to suggest substantial patient risk. METHODS:
      Using a demographically diverse, online sample, we compared the reactions of 1618
      adults in the United States who viewed visual line displays that included both
      standard range and harm anchor reference points ("Many doctors are not concerned
      until here") to displays that included either (1) only a standard range, (2)
      standard range plus evaluative categories (eg, "borderline high"), or (3) a color
      gradient showing degree of deviation from the standard range. RESULTS: Providing
      the harm anchor reference point significantly reduced perceived urgency of close
      to-normal alanine aminotransferase and creatinine results (P values <.001) but
      not generally for platelet count results. Notably, display type did not
      significantly alter perceptions of more extreme results in potentially harmful
      ranges. Harm anchors also substantially reduced the number of participants who
      wanted to contact their doctor urgently or go to the hospital about these test
      results. CONCLUSIONS: Presenting patients with evaluative cues regarding when
      test results become clinically concerning can reduce the perceived urgency of out
      of-range results that do not require immediate clinical action.

PMID- 29581089
TI  - Evaluation of an Internet-Based Behavioral Intervention to Improve Psychosocial
      Health Outcomes in Children With Insomnia (Better Nights, Better Days): Protocol
      for a Randomized Controlled Trial.
AB  - BACKGROUND: Up to 25% of 1- to 10-year-old children experience insomnia (ie,
      resisting bedtime, trouble falling asleep, night awakenings, and waking too early
      in the morning). Insomnia can be associated with excessive daytime sleepiness and
      negative effects on daytime functioning across multiple domains (eg, behavior,
      mood, attention, and learning). Despite robust evidence supporting the
      effectiveness of behavioral treatments for insomnia in children, very few
      children with insomnia receive these treatments, primarily due to a shortage of
      available treatment resources. OBJECTIVE: The Better Nights, Better Days (BNBD)
      internet-based program provides a readily accessible electronic health (eHealth)
      intervention to support parents in providing evidence-based care for insomnia in
      typically developing children. The purpose of the randomized controlled trial
      (RCT) is to evaluate the effectiveness of BNBD in treating insomnia in children
      aged between 1 and 10 years. METHODS: BNBD is a fully automated program,
      developed based on evidence-based interventions previously tested by the
      investigators, as well as on the extant literature on this topic. We describe the
      2-arm RCT in which participants (500 primary caregivers of children with insomnia
      residing in Canada) are assigned to intervention or usual care. RESULTS: The
      effects of this behavioral sleep eHealth intervention will be assessed at 4 and 8
      months postrandomization. Assessment includes both sleep (actigraphy, sleep
      diary) and daytime functioning of the children and daytime functioning of their
      parents. Results will be reported using the standards set out in the Consolidated
      Standards of Reporting Trials statement. CONCLUSIONS: If the intervention is
      supported by the results of the RCT, we plan to commercialize this program so
      that it is sustainable and available at a low cost to all families with internet
      access. TRIAL REGISTRATION: ClinicalTrials.gov NCT02243501;
      https://clinicaltrials.gov/show/NCT02243501 (Archived by WebCite at
      http://www.webcitation.org/6x8Z5pBui).

PMID- 29581090
TI  - Implications of Patient Portal Transparency in Oncology: Qualitative Interview
      Study on the Experiences of Patients, Oncologists, and Medical Informaticists.
AB  - BACKGROUND: Providing patients with unrestricted access to their electronic
      medical records through patient portals has impacted patient-provider
      communication and patients' personal health knowledge. However, little is known
      about how patient portals are used in oncology. OBJECTIVE: The aim of this study
      was to understand attitudes of the portal's adoption for oncology and to identify
      the advantages and disadvantages of using the portal to communicate and view
      medical information. METHODS: In-depth semistructured interviews were conducted
      with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists.
      Interviews were recorded, transcribed, and thematically analyzed to identify
      critical incidents and general attitudes encountered by participants. RESULTS:
      Two primary themes were discovered: (1) implementation practices influence
      attitudes, in which the decision-making and execution process of introducing
      portals throughout the hospital did not include the input of oncologists. Lack of
      oncologists' involvement led to a lack of knowledge about portal functionality,
      such as not knowing the time period when test results would be disclosed to
      patients; (2) perceptions of portals as communication tools varies by user type,
      meaning that each participant group (patients, oncologists, and medical
      informaticists) had varied opinions about how the portal should be used to
      transmit and receive information. Oncologists and medical informaticists had
      difficulty understanding one another's culture and communication processes in
      their fields, while patients had preferences for how they would like to receive
      communication, but it largely depended upon the type of test being disclosed.
      CONCLUSIONS: The majority of patients (54%, 19/35) who participated in this study
      viewed lab results or scan reports via the portal before being contacted by a
      clinician. Most were relatively comfortable with this manner of disclosure but
      still preferred face-to-face or telephone communication. Findings from this study
      indicate that portal education is needed for both patients and oncologists,
      especially when portals are implemented across entire health systems since highly
      specialized areas of medicine may have unique needs and uses. Patient portals in
      oncology can potentially alter the way diagnoses are delivered and how patients
      and oncologists communicate. Therefore, communication about the portal should be
      established during initial consultations so patients can decide whether they want
      to be informed in such a manner.

PMID- 29581091
TI  - How Online Quality Ratings Influence Patients' Choice of Medical Providers:
      Controlled Experimental Survey Study.
AB  - BACKGROUND: In recent years, the information environment for patients to learn
      about physician quality is being rapidly changed by Web-based ratings from both
      commercial and government efforts. However, little is known about how various
      types of Web-based ratings affect individuals' choice of physicians. OBJECTIVE:
      The objective of this research was to measure the relative importance of Web
      based quality ratings from governmental and commercial agencies on individuals'
      choice of primary care physicians. METHODS: In a choice-based conjoint experiment
      conducted on a sample of 1000 Amazon Mechanical Turk users in October 2016,
      individuals were asked to choose their preferred primary care physician from
      pairs of physicians with different ratings in clinical and nonclinical aspects of
      care provided by governmental and commercial agencies. RESULTS: The relative log
      odds of choosing a physician increases by 1.31 (95% CI 1.26-1.37; P<.001) and
      1.32 (95% CI 1.27-1.39; P<.001) units when the government clinical ratings and
      commercial nonclinical ratings move from 2 to 4 stars, respectively. The relative
      log odds of choosing a physician increases by 1.12 (95% CI 1.07-1.18; P<.001)
      units when the commercial clinical ratings move from 2 to 4 stars. The relative
      log odds of selecting a physician with 4 stars in nonclinical ratings provided by
      the government is 1.03 (95% CI 0.98-1.09; P<.001) units higher than a physician
      with 2 stars in this rating. The log odds of selecting a physician with 4 stars
      in nonclinical government ratings relative to a physician with 2 stars is 0.23
      (95% CI 0.13-0.33; P<.001) units higher for females compared with males. Similar
      star increase in nonclinical commercial ratings increases the relative log odds
      of selecting the physician by female respondents by 0.15 (95% CI 0.04-0.26;
      P=.006) units. CONCLUSIONS: Individuals perceive nonclinical ratings provided by
      commercial websites as important as clinical ratings provided by government
      websites when choosing a primary care physician. There are significant gender
      differences in how the ratings are used. More research is needed on whether
      patients are making the best use of different types of ratings, as well as the
      optimal allocation of resources in improving physician ratings from the
      government's perspective.

PMID- 29581092
TI  - Detecting Motor Impairment in Early Parkinson's Disease via Natural Typing
      Interaction With Keyboards: Validation of the neuroQWERTY Approach in an
      Uncontrolled At-Home Setting.
AB  - BACKGROUND: Parkinson's disease (PD) is the second most prevalent
      neurodegenerative disease and one of the most common forms of movement disorder.
      Although there is no known cure for PD, existing therapies can provide effective
      symptomatic relief. However, optimal titration is crucial to avoid adverse
      effects. Today, decision making for PD management is challenging because it
      relies on subjective clinical evaluations that require a visit to the clinic.
      This challenge has motivated recent research initiatives to develop tools that
      can be used by nonspecialists to assess psychomotor impairment. Among these
      emerging solutions, we recently reported the neuroQWERTY index, a new digital
      marker able to detect motor impairment in an early PD cohort through the analysis
      of the key press and release timing data collected during a controlled in-clinic
      typing task. OBJECTIVE: The aim of this study was to extend the in-clinic
      implementation to an at-home implementation by validating the applicability of
      the neuroQWERTY approach in an uncontrolled at-home setting, using the typing
      data from subjects' natural interaction with their laptop to enable remote and
      unobtrusive assessment of PD signs. METHODS: We implemented the data-collection
      platform and software to enable access and storage of the typing data generated
      by users while using their computer at home. We recruited a total of 60
      participants; of these participants 52 (25 people with Parkinson's and 27 healthy
      controls) provided enough data to complete the analysis. Finally, to evaluate
      whether our in-clinic-built algorithm could be used in an uncontrolled at-home
      setting, we compared its performance on the data collected during the controlled
      typing task in the clinic and the results of our method using the data passively
      collected at home. RESULTS: Despite the randomness and sparsity introduced by the
      uncontrolled setting, our algorithm performed nearly as well in the at-home data
      (area under the receiver operating characteristic curve [AUC] of 0.76 and
      sensitivity/specificity of 0.73/0.69) as it did when used to evaluate the in
      clinic data (AUC 0.83 and sensitivity/specificity of 0.77/0.72). Moreover, the
      keystroke metrics presented a strong correlation between the 2 typing settings,
      which suggests a minimal influence of the in-clinic typing task in users' normal
      typing. CONCLUSIONS: The finding that an algorithm trained on data from an in
      clinic setting has comparable performance with that tested on data collected
      through naturalistic at-home computer use reinforces the hypothesis that subtle
      differences in motor function can be detected from typing behavior. This work
      represents another step toward an objective, user-convenient, and quasi
      continuous monitoring tool for PD.

PMID- 29581093
TI  - Evolution of Cognitive Rehabilitation After Stroke From Traditional Techniques to
      Smart and Personalized Home-Based Information and Communication Technology
      Systems: Literature Review.
AB  - BACKGROUND: Neurological patients after stroke usually present cognitive deficits
      that cause dependencies in their daily living. These deficits mainly affect the
      performance of some of their daily activities. For that reason, stroke patients
      need long-term processes for their cognitive rehabilitation. Considering that
      classical techniques are focused on acting as guides and are dependent on help
      from therapists, significant efforts are being made to improve current
      methodologies and to use eHealth and Web-based architectures to implement
      information and communication technology (ICT) systems that achieve reliable,
      personalized, and home-based platforms to increase efficiency and level of
      attractiveness for patients and carers. OBJECTIVE: The goal of this work was to
      provide an overview of the practices implemented for the assessment of stroke
      patients and cognitive rehabilitation. This study puts together traditional
      methods and the most recent personalized platforms based on ICT technologies and
      Internet of Things. METHODS: A literature review has been distributed to a
      multidisciplinary team of researchers from engineering, psychology, and sport
      science fields. The systematic review has been focused on published scientific
      research, other European projects, and the most current innovative large-scale
      initiatives in the area. A total of 3469 results were retrieved from Web of
      Science, 284 studies from Journal of Medical Internet Research, and 15 European
      research projects from Community Research and Development Information Service
      from the last 15 years were reviewed for classification and selection regarding
      their relevance. RESULTS: A total of 7 relevant studies on the screening of
      stroke patients have been presented with 6 additional methods for the analysis of
      kinematics and 9 studies on the execution of goal-oriented activities. Meanwhile,
      the classical methods to provide cognitive rehabilitation have been classified in
      the 5 main techniques implemented. Finally, the review has been finalized with
      the selection of 8 different ICT-based approaches found in scientific-technical
      studies, 9 European projects funded by the European Commission that offer eHealth
      architectures, and other large-scale activities such as smart houses and the
      initiative City4Age. CONCLUSIONS: Stroke is one of the main causes that most
      negatively affect countries in the socioeconomic aspect. The design of new ICT
      based systems should provide 4 main features for an efficient and personalized
      cognitive rehabilitation: support in the execution of complex daily tasks,
      automatic error detection, home-based performance, and accessibility. Only 33% of
      the European projects presented fulfilled those requirements at the same time.
      For this reason, current and future large-scale initiatives focused on eHealth
      and smart environments should try to solve this situation by providing more
      complete and sophisticated platforms.

PMID- 29581094
TI  - Prenatal Remote Monitoring of Women With Gestational Hypertensive Diseases: Cost
      Analysis.
AB  - BACKGROUND: Remote monitoring in obstetrics is relatively new; some studies have
      shown its effectiveness for both mother and child. However, few studies have
      evaluated the economic impact compared to conventional care, and no cost analysis
      of a remote monitoring prenatal follow-up program for women diagnosed with
      gestational hypertensive diseases (GHD) has been published. OBJECTIVE: The aim of
      this study was to assess the costs of remote monitoring versus conventional care
      relative to reported benefits. METHODS: Patient data from the Pregnancy Remote
      Monitoring (PREMOM) study were used. Health care costs were calculated from
      patient-specific hospital bills of Ziekenhuis Oost-Limburg (Genk, Belgium) in
      2015. Cost comparison was made from three perspectives: the Belgian national
      health care system (HCS), the National Institution for Insurance of Disease and
      Disability (RIZIV), and costs for individual patients. The calculations were made
      for four major domains: prenatal follow-up, prenatal admission to the hospital,
      maternal and neonatal care at and after delivery, and total amount of costs. A
      simulation exercise was made in which it was calculated how much could be
      demanded of RIZIV for funding the remote monitoring service. RESULTS: A total of
      140 pregnancies were included, of which 43 received remote monitoring (30.7%) and
      97 received conventional care (69.2%). From the three perspectives, there were no
      differences in costs for prenatal follow-up. Compared to conventional care,
      remote monitoring patients had 34.51% less HCS and 41.72% less RIZIV costs for
      laboratory test results (HCS: mean ?0.00 [SD ?55.34] vs mean ?38.28 [SD ? 44.08],
      P<.001; RIZIV: mean ?21.09 [SD ?27.94] vs mean ?36.19 [SD ?41.36], P<.001) and a
      reduction of 47.16% in HCS and 48.19% in RIZIV costs for neonatal care (HCS: mean
      ?989.66 [SD ?3020.22] vs mean ?1872.92 [SD ?5058.31], P<.001; RIZIV: mean ?872.97
      [SD ?2761.64] vs mean ?1684.86 [SD ?4702.20], P<.001). HCS costs for medication
      were 1.92% lower in remote monitoring than conventional care (mean ?209.22 [SD
      ?213.32] vs mean ?231.32 [SD 67.09], P=.02), but were 0.69% higher for RIZIV
      (mean ?122.60 [SD ?92.02] vs mean ?121.78 [SD ?20.77], P<.001). Overall HCS costs
      for remote monitoring were mean ?4233.31 (SD ?3463.31) per person and mean
      ?4973.69 (SD ?5219.00) per person for conventional care (P=.82), a reduction of
      ?740.38 (14.89%) per person, with savings mainly for RIZIV of ?848.97 per person
      (23.18%; mean ?2797.42 [SD ?2905.18] vs mean ?3646.39 [SD ?4878.47], P=.19). When
      an additional fee of ?525.07 per month per pregnant woman for funding remote
      monitoring costs is demanded, remote monitoring is acceptable in their costs for
      HCS, RIZIV, and individual patients. CONCLUSIONS: In the current organization of
      Belgian health care, a remote monitoring prenatal follow-up of women with GHD is
      cost saving for the global health care system, mainly via savings for the
      insurance institution RIZIV.

PMID- 29581095
TI  - The Presence of Diabetes and Higher HbA1c Are Independently Associated With
      Adverse Outcomes After Surgery.
AB  - OBJECTIVE: Limited studies have examined the association between diabetes and
      HbA1c with postoperative outcomes. We investigated the association of diabetes,
      defined categorically, and the association of HbA1c as a continuous measure, with
      postoperative outcomes. RESEARCH DESIGN AND METHODS: In this prospective,
      observational study, we measured the HbA1c of surgical inpatients age >=54 years
      at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed
      with diabetes if they had preexisting diabetes or an HbA1c >=6.5% (48 mmol/mol)
      or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48
      mmol/mol). Patients with an HbA1c <5.7% (39 mmol/mol) were categorized as having
      normoglycemia. Baseline demographic and clinical data were obtained from hospital
      records, and patients were followed for 6 months. Random-effects logistic and
      negative binomial regression models were used for analysis, treating surgical
      units as random effects. We undertook classification and regression tree (CART)
      analysis to design a 6-month mortality risk model. RESULTS: Of 7,565 inpatients,
      30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson
      comorbidity index (excluding diabetes and age), estimated glomerular filtration
      rate, and length of surgery, diabetes was associated with increased 6-month
      mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05-1.58]; P = 0.014), major
      complications (1.32 [1.14-1.52]; P < 0.001), intensive care unit (ICU) admission
      (1.50 [1.28-1.75]; P < 0.001), mechanical ventilation (1.67 [1.32-2.10]; P <
      0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR]
      1.08 [95% CI 1.04-1.12]; P < 0.001). Each percentage increase in HbA1c was
      associated with increased major complications (aOR 1.07 [1.01-1.14]; P = 0.030),
      ICU admission (aOR 1.14 [1.07-1.21]; P < 0.001), and hospital LOS (aIRR 1.05
      [1.03-1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month
      mortality with diabetes in conjunction with other risk factors. CONCLUSIONS:
      Almost one-third of surgical inpatients age >=54 years had diabetes. Diabetes and
      higher HbA1c were independently associated with a higher risk of adverse outcomes
      after surgery.

PMID- 29581096
TI  - p110alpha of PI3K is necessary and sufficient for quiescence exit in adult muscle
      satellite cells.
AB  - Adult mouse muscle satellite cells (MuSCs) are quiescent in uninjured muscles.
      Upon injury, MuSCs exit quiescence in vivo to become activated, re-enter the cell
      cycle to proliferate, and differentiate to repair the damaged muscles. It remains
      unclear which extrinsic cues and intrinsic signaling pathways regulate quiescence
      exit during MuSC activation. Here, we demonstrated that inducible MuSC-specific
      deletion of p110alpha, a catalytic subunit of phosphatidylinositol 3-kinase
      (PI3K), rendered MuSCs unable to exit quiescence, resulting in severely impaired
      MuSC proliferation and muscle regeneration. Genetic reactivation of mTORC1, or
      knockdown of FoxOs, in p110alpha-null MuSCs partially rescued the above defects,
      making them key effectors downstream of PI3K in regulating quiescence exit. c-Jun
      was found to be a key transcriptional target of the PI3K/mTORC1 signaling axis
      essential for MuSC quiescence exit. Moreover, induction of a constitutively
      active PI3K in quiescent MuSCs resulted in spontaneous MuSC activation in
      uninjured muscles and subsequent depletion of the MuSC pool. Thus, PI3K-p110alpha
      is both necessary and sufficient for MuSCs to exit quiescence in response to
      activating signals.

PMID- 29581097
TI  - Spatial separation between replisome- and template-induced replication stress
      signaling.
AB  - Polymerase-blocking DNA lesions are thought to elicit a checkpoint response via
      accumulation of single-stranded DNA at stalled replication forks. However, as an
      alternative to persistent fork stalling, re-priming downstream of lesions can
      give rise to daughter-strand gaps behind replication forks. We show here that the
      processing of such structures by an exonuclease, Exo1, is required for timely
      checkpoint activation, which in turn prevents further gap erosion in S phase.
      This Rad9-dependent mechanism of damage signaling is distinct from the Mrc1
      dependent, fork-associated response to replication stress induced by conditions
      such as nucleotide depletion or replisome-inherent problems, but reminiscent of
      replication-independent checkpoint activation by single-stranded DNA Our results
      indicate that while replisome stalling triggers a checkpoint response directly at
      the stalled replication fork, the response to replication stress elicited by
      polymerase-blocking lesions mainly emanates from Exo1-processed, postreplicative
      daughter-strand gaps, thus offering a mechanistic explanation for the dichotomy
      between replisome- versus template-induced checkpoint signaling.

PMID- 29581098
TI  - Waking up muscle stem cells: PI3K signalling is ringing.

PMID- 29581099
TI  - Spot of bother: Bitot's spot.

PMID- 29581100
TI  - Resilience: surviving and thriving in the paediatric workplace.
AB  - The health of the medical workforce, within the UK, has been described as an
      unmet public health need. Reports of stress, burnout and ill health are
      continuing to rise. Burnout is when meaningful and challenging work becomes
      unpleasant and unfulfilling; energy turns into exhaustion; enthusiasm turns into
      cynicism and efficacy turns into ineffectiveness. Stress is an individual's
      physical and psychological response to single or multiple pressures. Low-level
      stress, or 'healthy stress', is essential. Stress becomes unhealthy when
      pressures exceed one's perceived ability to cope and the response to the
      pressures becomes counterproductive, leading to a decrease in performance.
      Resilience is the capability to develop and adapt to challenges and discover new
      ways forward, without negative consequences on one's well-being. This paper
      discusses stress and burnout within the healthcare profession; strategies to cope
      with the demands of the workplace through a reflective scenario, along with well
      being and mindfulness resources for managing stress and promoting resilience. The
      five ways to well-being and mindfulness practice are simple measures that can be
      built into one's daily life to increase resilience against excess stress and
      pressures. The coping matrix is a practical tool to encourage reflecting upon and
      developing one's own coping strategies. A good healthcare professional is one who
      is compassionate to themselves and their own well-being, enabling them to care
      and treat their patients.

PMID- 29581101
TI  - Catastrophic drug coverage: utilization insights from the Ontario Trillium Drug
      Program.
AB  - BACKGROUND: Catastrophic drug coverage programs help those with high drug-costs
      to reduce the burden of out-of-pocket expenses. We set out to measure changes in
      utilization, spending and demographic profiles of people accessing Ontario's
      catastrophic drug program, the Trillium Drug Program. METHODS: We conducted a
      cross-sectional time-series analysis examining quarterly utilization and spending
      trends among medications reimbursed by the Trillium Drug Program in Ontario,
      Canada from Jan. 1, 2000, to Dec. 31, 2016. In each of 2000, 2005, 2010 and 2015,
      we described the population of beneficiaries, including demographic information,
      health care utilization and medication utilization. RESULTS: Over our study
      period, use of the Trillium Drug Program increased threefold from 3.6
      beneficiaries per 1000 to 10.9 beneficiaries per 1000 Ontarians, and total
      government spending on the program increased by over 700%, reaching $487 million
      in 2016. Between 2000 and 2015, there was an increase in the number of
      beneficiaries who were under the age of 35 years (19.6% to 25.3%; p < 0.0001),
      did not have a hospital admission (68.3% to 80.5%; p < 0.0001) and had medium to
      high deductibles (2.3% to 8.0%; p < 0.0001). Further, there was a large increase
      in the percentage of users with drug claims greater than $1000 (3.4% to 10.4%; p
      < 0.0001) and those dispensed a high-cost biologic drug (1.6% to 5.5%; p <
      0.0001). INTERPRETATION: Increasing use of Ontario's catastrophic drug program
      highlights the growing burden of high drug prices for Canadians. With a growing
      number of expensive drugs being approved in Canada, we anticipate that spending
      and use of the catastrophic drug program will continue to expand.

PMID- 29581102
TI  - March 26th Question.

PMID- 29581104
TI  - GP contests claim that online provider passed CQC inspection "with flying
      colours".

PMID- 29581103
TI  - Data Generated by Quantitative Liquid Chromatography-Mass Spectrometry Proteomics
      Are Only the Start and Not the Endpoint: Optimization of Quantitative Concatemer
      Based Measurement of Hepatic Uridine-5'-Diphosphate-Glucuronosyltransferase
      Enzymes with Reference to Catalytic Activity.
AB  - Quantitative proteomic methods require optimization at several stages, including
      sample preparation, liquid chromatography-tandem mass spectrometry (LC-MS/MS),
      and data analysis, with the final analysis stage being less widely appreciated by
      end-users. Previously reported measurement of eight uridine-5'-diphospho
      glucuronosyltransferases (UGT) generated by two laboratories [using stable
      isotope-labeled (SIL) peptides or quantitative concatemer (QconCAT)] reflected
      significant disparity between proteomic methods. Initial analysis of QconCAT data
      showed lack of correlation with catalytic activity for several UGTs (1A4, 1A6,
      1A9, 2B15) and moderate correlations for UGTs 1A1, 1A3, and 2B7 (Rs = 0.40-0.79,
      P < 0.05; R2 = 0.30); good correlations were demonstrated between cytochrome P450
      activities and abundances measured in the same experiments. Consequently, a
      systematic review of data analysis, starting from unprocessed LC-MS/MS data, was
      undertaken, with the aim of improving accuracy, defined by correlation against
      activity. Three main criteria were found to be important: choice of monitored
      peptides and fragments, correction for isotope-label incorporation, and abundance
      normalization using fractional protein mass. Upon optimization, abundance
      activity correlations improved significantly for six UGTs (Rs = 0.53-0.87, P <
      0.01; R2 = 0.48-0.73); UGT1A9 showed moderate correlation (Rs = 0.47, P = 0.02;
      R2 = 0.34). No spurious abundance-activity relationships were identified.
      However, methods remained suboptimal for UGT1A3 and UGT1A9; here hydrophobicity
      of standard peptides is believed to be limiting. This commentary provides a
      detailed data analysis strategy and indicates, using examples, the significance
      of systematic data processing following acquisition. The proposed strategy offers
      significant improvement on existing guidelines applicable to clinically relevant
      proteins quantified using QconCAT.

PMID- 29581105
TI  - An Evolving Continuum of Care for the Kidney Disease Patient Will Help the
      Transplant Center Patient Navigator.

PMID- 29581106
TI  - What Else Can We Do to Ensure Transplant Equity for High-Risk Patients?

PMID- 29581107
TI  - Transplant Center Patient Navigator and Access to Transplantation among High-Risk
      Population: A Randomized, Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Barriers exist in access to kidney transplantation,
      where minority and patients with low socioeconomic status are less likely to
      complete transplant evaluation. The purpose of this study was to examine the
      effectiveness of a transplant center-based patient navigator in helping patients
      at high risk of dropping out of the transplant evaluation process access the
      kidney transplant waiting list. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: We
      conducted a randomized, controlled trial of 401 patients (n=196 intervention and
      n=205 control) referred for kidney transplant evaluation (January 2013 to August
      2014; followed through May 2016) at a single center. A trained navigator assisted
      intervention participants from referral to waitlisting decision to increase
      waitlisting (primary outcome) and decrease time from referral to waitlisting
      (secondary outcome). Time-dependent Cox proportional hazards models were used to
      determine differences in waitlisting between intervention and control patients.
      RESULTS: At study end, waitlisting was not significantly different among
      intervention (32%) versus control (26%) patients overall (P=0.17), and time from
      referral to waitlisting was 126 days longer for intervention patients. However,
      the effectiveness of the navigator varied from early (<500 days from referral) to
      late (>=500 days) follow-up. Although no difference in waitlisting was observed
      among intervention (50%) versus control (50%) patients in the early period
      (hazard ratio, 1.03; 95% confidence interval, 0.69 to 1.53), intervention
      patients were 3.3 times more likely to be waitlisted after 500 days (75% versus
      25%; hazard ratio, 3.31; 95% confidence interval, 1.20 to 9.12). There were no
      significant differences in intervention versus control patients who started
      evaluation (85% versus 79%; P=0.11) or completed evaluation (58% versus 51%;
      P=0.14); however, intervention patients had more living donor inquiries (18%
      versus 10%; P=0.03). CONCLUSIONS: A transplant center-based navigator targeting
      disadvantaged patients improved waitlisting but not until after 500 days of
      follow-up. However, the absolute effect was relatively small.

PMID- 29581108
TI  - VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response
      characteristics and binding sites.
AB  - Vitamin K reduction is catalyzed by 2 enzymes in vitro: the vitamin K 2,3-epoxide
      reductase complex subunit 1 (VKORC1) and its isozyme VKORC1-like1 (VKORC1L1). In
      vivo, VKORC1 reduces vitamin K to sustain gamma-carboxylation of vitamin K
      dependent proteins, including coagulation factors. Inhibition of VKORC1 by oral
      anticoagulants (OACs) is clinically used in therapy and in prevention of
      thrombosis. However, OACs also inhibit VKORC1L1, which was previously shown to
      play a role in intracellular redox homeostasis in vitro. Here, we report data for
      the first time on specific inhibition of both VKOR enzymes for various OACs and
      rodenticides examined in a cell-based assay. Effects on endogenous VKORC1 and
      VKORC1L1 were independently investigated in genetically engineered HEK 293T cells
      that were knocked out for the respective genes by CRISPR/Cas9 technology. In
      general, dose-responses for 4-hydroxycoumarins and 1,3-indandiones were enzyme
      dependent, with lower susceptibility for VKORC1L1 compared with VKORC1. In
      contrast, rodenticides exhibited nearly identical dose-responses for both
      enzymes. To explain the distinct inhibition pattern, we performed in silico
      modeling suggesting different warfarin binding sites for VKORC1 and VKORC1L1. We
      identified arginine residues at positions 38, 42, and 68 in the endoplasmatic
      reticulum luminal loop of VKORC1L1 responsible for charge-stabilized warfarin
      binding, resulting in a binding pocket that is diametrically opposite to that of
      VKORC1. In conclusion, our findings provide insight into structural and molecular
      drug binding on VKORC1, and especially on VKORC1L1.

PMID- 29581109
TI  - B-cell tumor development in Tet2-deficient mice.
AB  - The TET2 gene encodes an alpha-ketoglutarate-dependent dioxygenase able to
      oxidize 5-methylcytosine into 5-hydroxymethylcytosine, which is a step toward
      active DNA demethylation. TET2 is frequently mutated in myeloid malignancies but
      also in B- and T-cell malignancies. TET2 somatic mutations are also identified in
      healthy elderly individuals with clonal hematopoiesis. Tet2-deficient mouse
      models showed widespread hematological differentiation abnormalities, including
      myeloid, T-cell, and B-cell malignancies. We show here that, similar to what is
      observed with constitutive Tet2-deficient mice, B-cell-specific Tet2 knockout
      leads to abnormalities in the B1-cell subset and a development of B-cell
      malignancies after long latency. Aging Tet2-deficient mice accumulate clonal
      CD19+ B220low immunoglobulin M+ B-cell populations with transplantable ability
      showing similarities to human chronic lymphocytic leukemia, including CD5
      expression and sensitivity to ibrutinib-mediated B-cell receptor (BCR) signaling
      inhibition. Exome sequencing of Tet2-/- malignant B cells reveals C-to-T and G-to
      A mutations that lie within single-stranded DNA-specific activation-induced
      deaminase (AID)/APOBEC (apolipoprotein B messenger RNA editing enzyme, catalytic
      polypeptide-like) cytidine deaminases targeted motif, as confirmed by the lack of
      a B-cell tumor in compound Tet2-Aicda-deficient mice. Finally, we show that Tet2
      deficiency accelerates and exacerbates T-cell leukemia/lymphoma 1A-induced
      leukemogenesis. Together, our data establish that Tet2 deficiency predisposes to
      mature B-cell malignancies, which development might be attributed in part to AID
      mediated accumulating mutations and BCR-mediated signaling.

PMID- 29581110
TI  - Profiling of PDR1 and MSH2 in Candida glabrata Bloodstream Isolates from a
      Multicenter Study in China.
AB  - Among 158 Candida glabrata bloodstream isolates collected from numerous centers
      in China, a resistance to fluconazole was seen in 8.9%. Three isolates (1.9%)
      were resistant to all echinocandins. Multilocus sequence typing (MLST) revealed
      that sequence type 7 ([ST7] 65.8%) was the most common type, followed by ST3
      (7.6%). PDR1 polymorphisms were associated with the acquisition of fluconazole
      resistance in C. glabrata isolates, while MSH2 polymorphisms were associated with
      the STs and microsatellite genotypes, irrespective of fluconazole resistance.

PMID- 29581111
TI  - Combination of Amphotericin B and Terbinafine against Melanized Fungi Associated
      with Chromoblastomycosis.
AB  - Our in vitro studies showed that a combination of amphotericin B and terbinafine
      had synergistic effects against the majority of melanized fungi associated with
      chromoblastomycosis (CBM) and similar infections, including those with
      Cladophialophora carrionii, Cladophialophora arxii, Exophialadermatitidis,
      Exophialaspinifera, Fonsecaea monophora, Fonsecaea nubica, Fonsecaea pedrosoi,
      and Phialophora verrucosa. This drug combination could provide an option for the
      treatment of severe or unresponsive cases of CBM, particularly in cases due to
      species of Fonsecaea and Cladophialophora.

PMID- 29581112
TI  - Survival in Patients with Candida glabrata Bloodstream Infection Is Associated
      with Fluconazole Dose.
AB  - Robust pharmacodynamic indices that align fluconazole dose or exposure with
      outcomes in invasive candidiasis due to Candida glabrata remain elusive. The
      purpose of this retrospective multicenter study was to evaluate a cohort of 127
      patients with C. glabrata fungemia treated with fluconazole, using adjusted
      analyses to identify risk factors for 28-day death. No significant correlations
      were found between fluconazole area under the curve (AUC), AUC/MIC ratio, or MIC
      and survival. In multivariate logistic regression analyses, however, higher
      average fluconazole dose (odds ratio [OR], 1.006 [95% confidence interval [CI],
      1.001 to 1.010]; P = 0.008), average fluconazole dose of >=400 mg (OR, 3.965 [95%
      CI, 1.509 to 10.418]; P = 0.005), and higher fluconazole dose on day 1 of therapy
      (OR, 1.007 [95% CI, 1.002 to 1.011]; P = 0.002) were found to be independent
      predictors of 28-day survival. Additionally, the presence of a central venous
      catheter at the time of infection was found to be a significant risk factor for
      death. In conclusion, we found fluconazole dose to be an independent predictor of
      28-day survival for patients with C. glabrata fungemia, with doses of >=400
      mg/day being associated with 28-day survival rates approaching 90%. These data
      indicate the use and efficacy of fluconazole in the treatment of this serious
      infection. Aggressive dosing appears to be necessary when fluconazole is used for
      the treatment of C. glabrata fungemia, irrespective of MIC.

PMID- 29581113
TI  - Chemotherapy with Phage Lysins Reduces Pneumococcal Colonization of the
      Respiratory Tract.
AB  - Bacteriophage-borne lytic enzymes, also named lysins or enzybiotics, are
      efficient agents for the killing of bacterial pathogens. The colonization of the
      respiratory tract by Streptococcus pneumoniae is a prerequisite for the
      establishment of the infection process. Hence, we have evaluated the
      antibacterial activities of three different lysins against pneumococcal
      colonization using human nasopharyngeal and lung epithelial cells as well as a
      mouse model of nasopharyngeal colonization. The lysins tested were the wild-type
      Cpl-1, the engineered Cpl-7S, and the chimera Cpl-711. Moreover, we included
      amoxicillin as a comparator antibiotic. Human epithelial cells were infected with
      three different multidrug-resistant clinical isolates of S. pneumoniae followed
      by a single dose of the corresponding lysin. The antimicrobial activities of
      these lysins were also evaluated using a mouse nasopharyngeal carriage model. The
      exposure of the infected epithelial cells to Cpl-7S did not result in the killing
      of any of the pneumococcal strains investigated. However, the treatment with Cpl
      1 or Cpl-711 increased the killing of S. pneumoniae organisms adhered to both
      types of human epithelial cells, with Cpl-711 being more effective than Cpl-1, at
      subinhibitory concentrations. In addition, a treatment with amoxicillin had no
      effect on reducing the carrier state, whereas mice treated by the intranasal
      route with Cpl-711 showed significantly reduced nasopharyngeal colonization, with
      no detection of bacterial load in 20 to 40% of the mice. This study indicates
      that Cpl-1 and Cpl-711 lysins might be promising antimicrobial candidates for
      therapy against pneumococcal colonization.

PMID- 29581114
TI  - Determination of the Dynamically Linked Indices of Fosfomycin for Pseudomonas
      aeruginosa in the Hollow Fiber Infection Model.
AB  - Fosfomycin is the only expoxide antimicrobial and is currently under development
      in the United States as an intravenously administered product. We were interested
      in identifying the exposure indices most closely linked to its ability to kill
      bacterial cells and to suppress amplification of less susceptible subpopulations.
      We employed the hollow fiber infection model for this investigation and studied
      wild-type strain Pseudomonas aeruginosa PAO1. Because of anticipated rapid
      resistance emergence, we shortened the study duration to 24 h but sampled the
      system more intensively. Doses of 12 and 18 g/day and schedules of daily
      administration, administration every 8 h, and administration by continuous
      infusion for each daily dose were studied. We measured fosfomycin concentrations
      (by liquid chromatography-tandem mass spectrometry), the total bacterial burden,
      and the burden of less susceptible isolates. We applied a mathematical model to
      all the data simultaneously. There was a rapid emergence of resistance with all
      doses and schedules. Prior to resistance emergence, an initial kill of 2 to 3
      log10(CFU/ml) was observed. The model demonstrated that the area under the
      concentration-time curve/MIC ratio was linked to total bacterial kill, while the
      time that the concentration remained above the MIC (or, equivalently, the minimum
      concentration/MIC ratio) was linked to resistance suppression. These findings
      were also seen in other investigations with Enterobacteriaceae (in vitro systems)
      and P. aeruginosa (murine system). We conclude that for serious infections with
      high bacterial burdens, fosfomycin may be of value as a new therapeutic and may
      be optimized by administering the agent as a continuous or prolonged infusion or
      by use of a short dosing interval. For indications such as ventilator-associated
      bacterial pneumonia, it may be prudent to administer fosfomycin as part of a
      combination regimen.

PMID- 29581115
TI  - Clinical and Microbiological Characteristics of Candida guilliermondii and
      Candida fermentati.
AB  - A total of 46 clinical isolates of Candida guilliermondii and Candida famata were
      reidentified genetically, resulting in 27 C. guilliermondii and 12 Candida
      fermentati strains. The majority of C. guilliermondii strains, but not C.
      fermentati strains, were isolated from blood cultures. C. fermentati was more
      sensitive to antifungals, hydrogen peroxide, and killing by murine macrophages
      than was C. guilliermondii The C. guilliermondii isolates were echinocandin
      susceptible in vitro but resistant to micafungin in a murine model of invasive
      candidiasis.

PMID- 29581116
TI  - Antifungal Prophylaxis with Posaconazole Delayed-Release Tablet and Oral
      Suspension in a Real-Life Setting: Plasma Levels, Efficacy, and Tolerability.
AB  - We continuously determined posaconazole plasma concentrations (PPCs) in 61
      patients with hematological malignancies receiving posaconazole (PCZ) delayed
      release tablets (DRT; 48 patients; median duration of intake, 92 days) and PCZ
      oral solution (OS; 13 patients; median duration of intake, 124 days). PCZ DRT and
      OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48
      patients (71%) receiving DRT always had PPCs of >0.7 mg/liter, while 14 of 48
      patients (29%) had at least one PPC of <=0.7 mg/liter. In patients receiving OS,
      4 of 13 patients (31%) always had PPCs of >0.7 mg/liter, 6 of 13 patients (46%)
      had at least one PPC of <=0.7 mg/liter, and 3 (23%) patients never reached a PPC
      of 0.7 mg/liter. In patients with at least one determined PPC, the mean
      proportion of all PPCs of >0.7 mg/liter was 91% for PCZ DRT, whereas it was 52%
      for PCZ OS (P = 0.001). In the per sample analysis, PPCs were significantly more
      likely to be >0.7 mg/liter in patients receiving DRT than in patients receiving
      OS (PPCs were >0.7 mg/liter in 91.4% [297/325] of patients receiving DRT versus
      70.3% [85/121] of patients receiving OS; P < 0.001). Patients receiving PCZ DRT
      had higher proportions of PPCs of >0.7 mg/liter than patients receiving OS both
      in the per patient and in the per sample analyses. Two patients (3%) had side
      effects during PCZ prophylaxis, and one (2%) had fungal breakthrough infection.
      Therapeutic drug monitoring enables detection of extended periods of PPCs of
      <=0.7 mg/liter (e.g., due to nonadherence or graft-versus-host disease), which
      may also be associated with the loss of protective intracellular PCZ
      concentrations, regardless of the PCZ formulation.

PMID- 29581117
TI  - Pharmacokinetics and Pharmacodynamics of Fosfomycin and Its Activity against
      Extended-Spectrum-beta-Lactamase-, Plasmid-Mediated AmpC-, and Carbapenemase
      Producing Escherichia coli in a Murine Urinary Tract Infection Model.
AB  - Fosfomycin has become an attractive treatment alternative for urinary tract
      infections (UTIs) due to increasing multidrug resistance (MDR) in Escherichia
      coli In this study, we evaluated the pharmacokinetic (PK) and pharmacodynamic
      (PD) indices of fosfomycin and its in vivo activity in an experimental murine
      model of ascending UTI. Subcutaneous administration of fosfomycin showed that the
      mean peak plasma concentrations of fosfomycin were 36, 280, and 750 mg/liter
      following administration of a single dose of 0.75, 7.5, and 30 mg/mouse,
      respectively, with an elimination half-life of 28 min, and urine peak
      concentrations of 1,100, 33,400, and 70,000 mg/liter expected to be sustained
      above 1 mg/liter (MIC of the test strain, NU14) for 5, 8, and 9.5 h,
      respectively. The optimal PK/PD indices for reducing urine colony counts (number
      of CFU per milliliter) were determined to be the area under the concentration
      time curve/MIC from 0 to 72 h and the maximum concentration/MIC on the basis of
      the dose-dependent bloodstream PK and the results of an evaluation of six dosing
      regimens. With a dosing regimen of 15 mg/mouse twice (every 36 h), fosfomycin
      significantly reduced the number of CFU per milliliter of all susceptible strains
      in urine, including clinical MDR strains, except for one clinical strain (P =
      0.062). Variable degrees of reduction were observed in the bladder and kidneys.
      No significant reductions in the number of CFU per milliliter were observed with
      the resistant strains. In conclusion, fosfomycin shows concentration-dependent in
      vivo activity, and the results suggest that fosfomycin is an effective
      alternative to carbapenems in treating MDR E. coli in uncomplicated UTIs. The
      data on the effectiveness of fosfomycin against the MDR isolates along with the
      results of PK/PD modeling should facilitate the further development of improved
      recommendations for its clinical use.

PMID- 29581118
TI  - Molecular Characterization of OXA-198 Carbapenemase-Producing Pseudomonas
      aeruginosa Clinical Isolates.
AB  - Carbapenemase-producing Pseudomonadaceae have increasingly been reported
      worldwide, with an ever-increasing heterogeneity of carbapenem resistance
      mechanisms, depending on the bacterial species and the geographical location. OXA
      198 is a plasmid-encoded class D beta-lactamase involved in carbapenem resistance
      in one Pseudomonas aeruginosa isolate from Belgium. In the setting of a
      multicenter survey of carbapenem resistance in P. aeruginosa strains in Belgian
      hospitals in 2013, three additional OXA-198-producing P. aeruginosa isolates
      originating from patients hospitalized in one hospital were detected. To reveal
      the molecular mechanism underlying the reduced susceptibility to carbapenems, MIC
      determinations, whole-genome sequencing, and PCR analyses to confirm the genetic
      organization were performed. The plasmid harboring the blaOXA-198 gene was
      characterized, along with the genetic relatedness of the four P. aeruginosa
      isolates. The blaOXA-198 gene was harbored on a class 1 integron carried by an
      ~49-kb IncP-type plasmid proposed as IncP-11. The same plasmid was present in all
      four P. aeruginosa isolates. Multilocus sequence typing revealed that the
      isolates all belonged to sequence type 446, and single-nucleotide polymorphism
      analysis revealed only a few differences between the isolates. This report
      describes the structure of a 49-kb plasmid harboring the blaOXA-198 gene and
      presents the first description of OXA-198-producing P. aeruginosa isolates
      associated with a hospital-associated cluster episode.

PMID- 29581119
TI  - Genetic Relationships among Multidrug-Resistant Salmonella enterica Serovar
      Typhimurium Strains from Humans and Animals.
AB  - We identified 20 to 22 resistance genes, carried in four incompatibility groups
      of plasmids, in each of five genetically closely related Salmonella enterica
      serovar Typhimurium strains recovered from humans, pigs, and chickens. The genes
      conferred resistance to aminoglycosides, chloramphenicol, sulfonamides,
      trimethoprim, tetracycline, fluoroquinolones, extended-spectrum cephalosporins
      and cefoxitin, and azithromycin. This study demonstrates the transmission of
      multidrug-resistant Salmonella strains among humans and food animals and may be
      the first identification of mphA in azithromycin-resistant Salmonella strains in
      Taiwan.

PMID- 29581120
TI  - Influence of Reactive Oxygen Species on De Novo Acquisition of Resistance to
      Bactericidal Antibiotics.
AB  - The radical-based theory proposes that three major classes of bactericidal
      antibiotics, i.e., beta-lactams, quinolones, and aminoglycosides, have in common
      the downstream formation of lethal levels of reactive oxygen species (ROS) as
      part of the killing mechanism. If bactericidal antibiotics exhibit a common
      mechanism, then it is to be expected that the acquisition of resistance against
      these drugs would have some shared traits as well. Indeed, cells made resistant
      to one bactericidal antibiotic more rapidly became resistant to another. This
      effect was absent after induced resistance to a bacteriostatic drug. De novo
      acquisition of resistance to one bactericidal antibiotic provided partial
      protection to killing by bactericidal antibiotics from a different class. This
      protective effect was observed in short-term experiments. No protective effect
      was detected during 24-h exposures, suggesting that cross-resistance did not
      occur. In the wild-type strain, exposure to bactericidal antibiotics increased
      intracellular ROS levels. This increase in ROS levels was not observed when
      strains resistant to these drugs were exposed to the same concentrations. These
      results indicate that de novo acquisition of resistance to the bactericidal drugs
      tested involves a common cellular response that provides protection against ROS
      accumulation upon exposure to this type of antibiotics. A central mechanism or at
      least a few common elements within the separate mechanisms possibly play a role
      during the acquisition of antibiotic resistance.

PMID- 29581121
TI  - Dextromethorphan Attenuates NADPH Oxidase-Regulated Glycogen Synthase Kinase
      3beta and NF-kappaB Activation and Reduces Nitric Oxide Production in Group A
      Streptococcal Infection.
AB  - Group A Streptococcus (GAS) is an important human pathogen that causes a wide
      spectrum of diseases, including necrotizing fasciitis and streptococcal toxic
      shock syndrome. Dextromethorphan (DM), an antitussive drug, has been demonstrated
      to efficiently reduce inflammatory responses, thereby contributing to an
      increased survival rate of GAS-infected mice. However, the anti-inflammatory
      mechanisms underlying DM treatment in GAS infection remain unclear. DM is known
      to exert neuroprotective effects through an NADPH oxidase-dependent regulated
      process. In the present study, membrane translocation of NADPH oxidase subunit
      p47phox and subsequent reactive oxygen species (ROS) generation induced by GAS
      infection were significantly inhibited via DM treatment in RAW264.7 murine
      macrophage cells. Further determination of proinflammatory mediators revealed
      that DM effectively suppressed inducible nitric oxide synthase (iNOS) expression
      and NO, tumor necrosis factor alpha, and interleukin-6 generation in GAS-infected
      RAW264.7 cells as well as in air-pouch-infiltrating cells from GAS/DM-treated
      mice. GAS infection caused AKT dephosphorylation, glycogen synthase kinase-3beta
      (GSK-3beta) activation, and subsequent NF-kappaB nuclear translocation, which
      were also markedly inhibited by treatment with DM and an NADPH oxidase inhibitor,
      diphenylene iodonium. These results suggest that DM attenuates GAS infection
      induced overactive inflammation by inhibiting NADPH oxidase-mediated ROS
      production that leads to downregulation of the GSK-3beta/NF-kappaB/NO signaling
      pathway.

PMID- 29581122
TI  - Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients.
AB  - To date, there is no information on the intravenous (i.v.) posaconazole
      pharmacokinetics for intensive care unit (ICU) patients. This prospective
      observational study aimed to describe the pharmacokinetics of a single dose of
      i.v. posaconazole in critically ill patients. Patients with no history of allergy
      to triazole antifungals and requiring systemic antifungal therapy were enrolled
      if they were aged >=18 years, central venous access was available, they were not
      pregnant, and they had not received prior posaconazole or drugs interacting with
      posaconazole. A single dose of 300 mg posaconazole was administered over 90 min.
      Total plasma concentrations were measured from serial plasma samples collected
      over 48 h, using a validated chromatographic method. The pharmacokinetic data set
      was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled
      with the following characteristics: median age, 46 years (interquartile range
      [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median
      albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR)
      pharmacokinetic parameter estimates were as follows: observed maximum
      concentration during sampling period (Cmax), 1,702 ng/ml (1,352 to 2,141 ng/ml);
      area under the concentration-time curve from zero to infinity (AUC0-infinity),
      17,932 ng . h/ml (13,823 to 27,905 ng . h/ml); clearance (CL), 16.8 liters/h
      (11.1 to 21.7 liters/h); and volume of distribution (V), 529.1 liters (352.2 to
      720.6 liters). The V and CL were greater than 2-fold and the AUC0-infinity was
      39% of the values reported for heathy volunteers. The AUC0-infinity was only 52%
      of the steady-state AUC0-24 reported for hematology patients. The median of
      estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163
      ng/ml), which is within but close to the lower end of the previously recommended
      therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different
      pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients
      compared to those in healthy volunteers and hematology patients.

PMID- 29581123
TI  - CrpP Is a Novel Ciprofloxacin-Modifying Enzyme Encoded by the Pseudomonas
      aeruginosa pUM505 Plasmid.
AB  - The pUM505 plasmid, isolated from a clinical Pseudomonas aeruginosa isolate,
      confers resistance to ciprofloxacin (CIP) when transferred into the standard P.
      aeruginosa strain PAO1. CIP is an antibiotic of the quinolone family that is used
      to treat P. aeruginosa infections. In silico analysis, performed to identify CIP
      resistance genes, revealed that the 65-amino-acid product encoded by the orf131
      gene in pUM505 displays 40% amino acid identity to the Mycobacterium smegmatis
      aminoglycoside phosphotransferase (an enzyme that phosphorylates and inactivates
      aminoglycoside antibiotics). We cloned orf131 (renamed crpP, for ciprofloxacin
      resistance protein, plasmid encoded) into the pUCP20 shuttle vector. The
      resulting recombinant plasmid, pUC-crpP, conferred resistance to CIP on
      Escherichia coli strain J53-3, suggesting that this gene encodes a protein
      involved in CIP resistance. Using coupled enzymatic analysis, we determined that
      the activity of CrpP on CIP is ATP dependent, while little activity against
      norfloxacin was detected, suggesting that CIP may undergo phosphorylation. Using
      a recombinant His-tagged CrpP protein and liquid chromatography-tandem mass
      spectrometry, we also showed that CIP was phosphorylated prior to its
      degradation. Thus, our findings demonstrate that CrpP, encoded on the pUM505
      plasmid, represents a new mechanism of CIP resistance in P. aeruginosa, which
      involves phosphorylation of the antibiotic.

PMID- 29581124
TI  - Time to Endovascular Treatment and Outcome in Acute Ischemic Stroke: MR CLEAN
      Registry Results.
AB  - BACKGROUND: Randomized, clinical trials in selected acute ischemic stroke
      patients reported that for every hour delay of endovascular treatment (EVT),
      chances of functional independence diminish by up to 3.4%. These findings may not
      be fully generalizable to clinical practice because of strict in- and exclusion
      criteria in these trials. Therefore, we aim to assess the association of time to
      EVT with functional outcome in current, everyday clinical practice. METHODS: The
      MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular
      Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing,
      prospective, observational study in all centers that perform EVT in The
      Netherlands. Data were analyzed from patients treated between March 2014 and June
      2016. In the primary analysis we assessed the association of time from stroke
      onset to start of EVT and time from stroke onset to successful reperfusion with
      functional outcome (measured with the modified Rankin Scale), by means of ordinal
      logistic regression. RESULTS: We analyzed 1488 patients with acute ischemic
      stroke who underwent EVT. An increased time to start of EVT was associated with
      worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95%
      confidence interval, 0.77-0.89) and a 2.2% increase in mortality. Every hour
      increase from stroke onset to EVT start resulted in a 5.3% decreased probability
      of functional independence (modified Rankin Scale, 0-2). In the 742 patients with
      successful reperfusion, every hour increase from stroke onset to reperfusion was
      associated with a 7.7% decreased probability of functional independence.
      CONCLUSIONS: Time to EVT for acute ischemic stroke in current clinical practice
      is strongly associated with functional outcome. Our data suggest that this
      association might be even stronger than previously suggested in reports on more
      selected patient populations from randomized, controlled trials. These findings
      emphasize that functional outcome of EVT patients can be greatly improved by
      shortening onset to treatment times.

PMID- 29581125
TI  - Prevalence and Predictors of Cholesterol Screening, Awareness, and Statin
      Treatment Among US Adults With Familial Hypercholesterolemia or Other Forms of
      Severe Dyslipidemia (1999-2014).
AB  - BACKGROUND: Familial hypercholesterolemia (FH) and other extreme elevations in
      low-density lipoprotein cholesterol significantly increase the risk of
      atherosclerotic cardiovascular disease; however, recent data suggest that
      prescription rates for statins remain low in these patients. National rates of
      screening, awareness, and treatment with statins among individuals with FH or
      severe dyslipidemia are unknown. METHODS: Data from the 1999 to 2014 National
      Health and Nutrition Examination Survey were used to estimate prevalence rates of
      self-reported screening, awareness, and statin therapy among US adults (n=42 471
      weighted to represent 212 million US adults) with FH (defined using the Dutch
      Lipid Clinic criteria) and with severe dyslipidemia (defined as low-density
      lipoprotein cholesterol levels >=190 mg/dL). Logistic regression was used to
      identify sociodemographic and clinical correlates of hypercholesterolemia
      awareness and statin therapy. RESULTS: The estimated US prevalence of
      definite/probable FH was 0.47% (standard error, 0.03%) and of severe dyslipidemia
      was 6.6% (standard error, 0.2%). The frequency of cholesterol screening and
      awareness was high (>80%) among adults with definite/probable FH or severe
      dyslipidemia; however, statin use was uniformly low (52.3% [standard error, 8.2%]
      of adults with definite/probable FH and 37.6% [standard error, 1.2%] of adults
      with severe dyslipidemia). Only 30.3% of patients with definite/probable FH on
      statins were taking a high-intensity statin. The prevalence of statin use in
      adults with severe dyslipidemia increased over time (from 29.4% to 47.7%) but not
      faster than trends in the general population (from 5.7% to 17.6%). Older age,
      health insurance status, having a usual source of care, diabetes mellitus,
      hypertension, and having a personal history of early atherosclerotic
      cardiovascular disease were associated with higher statin use. CONCLUSIONS:
      Despite the high prevalence of cholesterol screening and awareness, only ~50% of
      adults with FH are on statin therapy, with even fewer prescribed a high-intensity
      statin; young and uninsured patients are at the highest risk for lack of
      screening and for undertreatment. This study highlights an imperative to improve
      the frequency of cholesterol screening and statin prescription rates to better
      identify and treat this high-risk population. Additional studies are needed to
      better understand how to close these gaps in screening and treatment.

PMID- 29581126
TI  - SDF-1 Is an Autocrine Insulin-Desensitizing Factor in Adipocytes.
AB  - Insulin desensitization occurs not only under the obese diabetic condition but
      also in the fasting state. However, little is known about the common secretory
      factor(s) that are regulated under these two insulin-desensitized conditions.
      Here, using database analysis and in vitro and in vivo experiments, we identified
      stromal derived factor-1 (SDF-1) as an insulin-desensitizing factor in
      adipocytes, overexpressed in both fasting and obese adipose tissues. Exogenously
      added SDF-1 induced extracellular signal-regulated kinase signal, which
      phosphorylated and degraded IRS-1 protein in adipocytes, decreasing insulin
      mediated signaling and glucose uptake. In contrast, knockdown of endogenous SDF-1
      or inhibition of its receptor in adipocytes markedly increased IRS-1 protein
      levels and enhanced insulin sensitivity, indicating the autocrine action of SDF
      1. In agreement with these findings, adipocyte-specific ablation of SDF-1
      enhanced insulin sensitivity in adipose tissues and in the whole body. These
      results point to a novel regulatory mechanism of insulin sensitivity mediated by
      adipose autocrine SDF-1 action and provide a new insight into the process of
      insulin desensitization in adipocytes.

PMID- 29581127
TI  - Acceptability of text messages for safety netting patients with low-risk cancer
      symptoms: a qualitative study.
AB  - BACKGROUND: Safety netting is an important diagnostic strategy for patients
      presenting to primary care with potential (low-risk) cancer symptoms. Typically,
      this involves asking patients to return if symptoms persist. However, this relies
      on patients re-appraising their symptoms and making follow-up appointments, which
      could contribute to delays in diagnosis. Text messaging is increasingly used in
      primary care to communicate with patients, and could be used to improve safety
      netting. AIM: To explore the acceptability and feasibility of using text messages
      to safety net patients presenting with low-risk cancer symptoms in GP primary
      care (txt-netting). DESIGN AND SETTING: Qualitative focus group and interview
      study with London-based GPs. METHOD: Participants were identified using
      convenience sampling methods. Five focus groups and two interviews were conducted
      with 22 GPs between August and December 2016. Sessions were audiorecorded,
      transcribed verbatim, and analysed using thematic analysis. RESULTS: GPs were
      amenable to the concept of using text messages in cancer safety netting,
      identifying it as an additional tool that could help manage patients and promote
      symptom awareness. There was wide variation in GP preferences for text message
      content, and a number of important potential barriers to txt-netting were
      identified. Concerns were raised about the difficulties of conveying complex
      safety netting advice within the constraints of a text message, and about
      confidentiality, widening inequalities, and workload implications. CONCLUSION:
      Text messages were perceived to be an acceptable potential strategy for safety
      netting patients with low-risk cancer symptoms. Further work is needed to ensure
      it is cost-effective, user friendly, confidential, and acceptable to patients.

PMID- 29581128
TI  - Improving palliative care provision in primary care: a pre- and post-survey
      evaluation among PaTz groups.
AB  - BACKGROUND: In PaTz (PAlliatieve Thuis Zorg, palliative care at home), modelled
      after the Gold Standards Framework, GPs and community nurses meet on a regular
      basis to identify patients with palliative care needs (the PaTz register), and to
      discuss care for these patients. AIM: To study the effects of the implementation
      of PaTz, and provide additional analyses on two important elements: the PaTz
      register and patient discussions. DESIGN AND SETTING: A pre- and post-evaluation
      among Dutch GPs (n = 195 before the start of PaTz; n = 166, 1 year after the
      start of PaTz). The GPs also provided data on recently deceased patients (n = 460
      before the start of PaTz; n = 305 14 months after the start of PaTz). METHOD: GPs
      from all 37 PaTz groups filled in questionnaires. Pre- and post-test differences
      were analysed using multilevel analyses to adjust for PaTz group. RESULTS:
      Identification of patients with palliative care needs was done systematically for
      more patients after implementation of PaTz compared with before (54.3% versus
      17.6%). After implementation, 64.8% of deceased patients had been included on the
      PaTz register. For these patients, when compared with patients not included on
      the PaTz register, preferred place of death was more likely to be known (88.1% of
      patients not on the register and 97.3% of deceased patients included on the
      register), GPs were more likely to have considered a possible death sooner (>1
      month before death: 53.0% and 80.2%), and conversations on life expectancy,
      physical complaints, existential issues, and possibilities of care occurred more
      often (60.8% and 81.3%; 68.6% and 86.1%; 22.5% and 34.2%; 60.8% and 84.0%,
      respectively). CONCLUSIONS: Implementation of PaTz improved systematic
      identification of palliative care patients within the GP practice. Use of the
      PaTz register has added value.

PMID- 29581129
TI  - Computer screening for palliative care needs in primary care: a mixed-methods
      study.
AB  - BACKGROUND: Though the majority of people could benefit from palliative care
      before they die, most do not receive this approach, especially those with
      multimorbidity and frailty. GPs find it difficult to identify such patients. AIM:
      To refine and evaluate the utility of a computer application (AnticiPal) to help
      primary care teams screen their registered patients for people who could benefit
      from palliative care. DESIGN AND SETTING: A mixed-methods study of eight GP
      practices in Scotland, conducted in 2016-2017. METHOD: After a search development
      cycle the authors adopted a mixed-methods approach, combining analysis of the
      number of people identified by the search with qualitative observations of the
      computer search as used by primary care teams, and interviews with professionals
      and patients. RESULTS: The search identified 0.8% of 62 708 registered patients.
      A total of 27 multidisciplinary meetings were observed, and eight GPs and 10
      patients were interviewed. GPs thought the search identified many unrecognised
      patients with advanced multimorbidity and frailty, but were concerned about
      workload implications of assessment and care planning. Patients and carers
      endorsed the value of proactive identification of people with advanced illness.
      CONCLUSION: GP practices can use computer searching to generate lists of patients
      for review and care planning. The challenges of starting a conversation about the
      future remain. However, most patients regard key components of palliative care
      (proactive planning, including sharing information with urgent care services) as
      important. Screening for people with deteriorating health at risk from unplanned
      care is a current focus for quality improvement and should not be limited by
      labelling it solely as 'palliative care'.

PMID- 29581130
TI  - Primary Care Outcomes Questionnaire: psychometric testing of a new instrument.
AB  - BACKGROUND: Patients attend primary care for many reasons and to achieve a range
      of possible outcomes. There is currently no Patient Reported Outcome Measure
      (PROM) designed to capture these diverse outcomes, and trials of interventions in
      primary care may thus fail to detect beneficial effects. AIM: This study
      describes the psychometric testing of the Primary Care Outcomes Questionnaire
      (PCOQ), which was designed to capture a broad range of outcomes relevant to
      primary care. DESIGN AND SETTING: Questionnaires were administered in primary
      care in South West England. METHOD: Patients completed the PCOQ in GP waiting
      rooms before a consultation, and a second questionnaire, including the PCOQ and
      seven comparator PROMs, after 1 week. Psychometric testing included exploratory
      factor analysis on the PCOQ, internal consistency, correlation coefficients
      between domain scores and comparator measures, and repeated measures effect sizes
      indicating change across 1 week. RESULTS: In total, 602 patients completed the
      PCOQ at baseline, and 264 (44%) returned the follow-up questionnaire. Exploratory
      factor analysis suggested four dimensions underlying the PCOQ items: health and
      wellbeing, health knowledge and self-care, confidence in health provision, and
      confidence in health plan. Each dimension was internally consistent and
      correlated as expected with comparator PROMs, providing evidence of construct
      validity. Patients reporting an improvement in their main problem exhibited small
      to moderate improvements in relevant domain scores on the PCOQ. CONCLUSION: The
      PCOQ was acceptable, feasible, showed strong psychometric properties, and was
      responsive to change. It is a promising new tool for assessment of outcomes of
      primary care interventions from a patient perspective.

PMID- 29581132
TI  - Biomarker Discovery from We to Me: Is Learning from Each Patient a New Approach?
AB  - The immune response is a dynamic multistep process with a complex system
      regulation. Identification of predictive biomarkers is therefore challenging.
      Deep investigation of an exceptional responder to pembrolizumab in ovarian cancer
      identifies a new mechanism of response and highlights the interest of
      individualized medicine strategy. Clin Cancer Res; 24(14); 3233-5. (c)2018
      AACRSee related article by Bellone et al., p. 3282.

PMID- 29581131
TI  - Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple
      Negative Breast Cancer.
AB  - Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are
      associated with improved survival in triple-negative breast cancer (TNBC). We
      investigated whether higher peripheral lymphocyte counts are associated with
      lower breast cancer-specific mortality (BCM) and overall mortality (OM) in
      TNBC.Experimental Design: Data on treatments and diagnostic tests from electronic
      medical records of two health care systems were linked with demographic,
      clinical, pathologic, and mortality data from the California Cancer Registry.
      Multivariable regression models adjusted for age, race/ethnicity, socioeconomic
      status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy
      use, and germline BRCA1/2 mutations were used to evaluate associations between
      absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data
      available, we explored the relationship between TILs and peripheral lymphocyte
      counts.Results: A total of 1,463 stage I-III TNBC patients were diagnosed from
      2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1
      year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever
      lymphopenic (minimum ALC <1.0 K/MUL). On multivariable analysis, higher minimum
      ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95%
      confidence interval (CI), 0.16-0.35] and BCM (HR = 0.19; CI, 0.11-0.34). Five
      year probability of BCM was 15% for patients who were ever lymphopenic versus 4%
      for those who were not. An exploratory analysis (n = 70) showed a significant
      association between TILs and higher peripheral lymphocyte counts during
      neoadjuvant chemotherapy.Conclusions: Higher peripheral lymphocyte counts
      predicted lower mortality from early-stage, potentially curable TNBC, suggesting
      that immune function may enhance the effectiveness of early TNBC treatment. Clin
      Cancer Res; 24(12); 2851-8. (c)2018 AACR.

PMID- 29581133
TI  - The Long Neglected Player: Modeling Tumor Uptake to Guide Optimal Dosing.
AB  - Pharmacokinetic modeling, traditionally using drug exposure, is widely used to
      support decision-making in translational medicine and patient care. The
      development of mechanistic computational models that integrate drug
      concentrations at the site of action making use of existing knowledge opens a new
      paradigm in optimal dosing. Clin Cancer Res; 24(14); 3236-8. (c)2018 AACRSee
      related article by Ribba et al., p. 3325.

PMID- 29581134
TI  - Data Analysis Strategies in Medical Imaging.
AB  - Radiographic imaging continues to be one of the most effective and clinically
      useful tools within oncology. Sophistication of artificial intelligence has
      allowed for detailed quantification of radiographic characteristics of tissues
      using predefined engineered algorithms or deep learning methods. Precedents in
      radiology as well as a wealth of research studies hint at the clinical relevance
      of these characteristics. However, critical challenges are associated with the
      analysis of medical imaging data. Although some of these challenges are specific
      to the imaging field, many others like reproducibility and batch effects are
      generic and have already been addressed in other quantitative fields such as
      genomics. Here, we identify these pitfalls and provide recommendations for
      analysis strategies of medical imaging data, including data normalization,
      development of robust models, and rigorous statistical analyses. Adhering to
      these recommendations will not only improve analysis quality but also enhance
      precision medicine by allowing better integration of imaging data with other
      biomedical data sources. Clin Cancer Res; 24(15); 3492-9. (c)2018 AACR.

PMID- 29581136
TI  - Arterial injury at LI4.

PMID- 29581135
TI  - ER+ Breast Cancers Resistant to Prolonged Neoadjuvant Letrozole Exhibit an E2F4
      Transcriptional Program Sensitive to CDK4/6 Inhibitors.
AB  - Purpose: This study aimed to identify biomarkers of resistance to endocrine
      therapy in estrogen receptor-positive (ER+) breast cancers treated with prolonged
      neoadjuvant letrozole.Experimental Design: We performed targeted DNA and RNA
      sequencing in 68 ER+ breast cancers from patients treated with preoperative
      letrozole (median, 7 months).Results: Twenty-four tumors (35%) exhibited a PEPI
      score >=4 and/or recurred after a median of 58 months and were considered
      endocrine resistant. Integration of the 47 most upregulated genes (log FC > 1,
      FDR < 0.03) in letrozole-resistant tumors with transcription-binding data showed
      significant overlap with 20 E2F4-regulated genes (P = 2.56E-15). In patients
      treated with the CDK4/6 inhibitor palbociclib before surgery, treatment
      significantly decreased expression of 24 of the 47 most upregulated genes in
      letrozole-resistant tumors, including 18 of the 20 E2F4 target genes. In long
      term estrogen-deprived ER+ breast cancer cells, palbociclib also downregulated
      all 20 E2F4 target genes and P-RB levels, whereas the ER downregulator
      fulvestrant or paclitaxel only partially suppressed expression of this set of
      genes and had no effect on P-RB. Finally, an E2F4 activation signature was
      strongly associated with resistance to aromatase inhibitors in the ACOSOG Z1031B
      neoadjuvant trial and with an increased risk of relapse in adjuvant-treated ER+
      tumors in METABRIC.Conclusions: In tumors resistant to prolonged neoadjuvant
      letrozole, we identified a gene expression signature of E2F4 target activation.
      CDK4/6 inhibition suppressed E2F4 target gene expression in estrogen-deprived ER+
      breast cancer cells and in patients' ER+ tumors, suggesting a potential benefit
      of adjuvant CDK4/6 inhibitors in patients with ER+ breast cancer who fail to
      respond to preoperative estrogen deprivation. Clin Cancer Res; 24(11); 2517-29.
      (c)2018 AACR.

PMID- 29581137
TI  - Treatment of polycystic ovary syndrome with acupuncture.

PMID- 29581138
TI  - Acupuncture in the emergency department: a systematic review of randomised
      controlled trials.
AB  - INTRODUCTION: A comprehensive review of both English and Chinese language
      literature to inform acupuncture practice in emergency department (ED) settings
      is lacking. Accordingly, we aimed to conduct a systematic review of English and
      Chinese randomised controlled trials (RCTs) of acupuncture use in the ED.
      METHODS: Four English databases (Embase, PubMed, AMED and CENTRAL) and two
      Chinese databases (CNKI and Wanfang) were systematically searched using the
      keywords 'acupuncture' and 'emergency department', followed by a bibliographic
      search of references. The data were extracted and assessed by two independent
      authors. RCTs were selected based on pre-defined criteria. Data were extracted
      and a risk of bias assessment was performed using the Cochrane risk of bias tool.
      The quality of evidence was rated using the Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) approach. RESULTS: In total, 1461
      articles were screened and six RCTs involving 651 patients were included. For
      various acute pain conditions, acupuncture was superior to sham acupuncture, more
      effective than intravenous morphine, comparable to conventional ED treatment, and
      superior to standard ED care alone when used on an adjuvant basis; however, the
      overall level of evidence was low. Studies that applied acupuncture in
      hypertension and cardiac arrest were deemed to be at high risk of bias, and the
      level of evidence for these outcomes was very low. No major adverse events were
      reported in the included studies. CONCLUSION: There is a lack of high-quality
      evidence to support the use of acupuncture in the ED. Multicentre RCTs with
      rigorous designs are warranted.

PMID- 29581139
TI  - Regulation of the IL-33/ST2 pathway contributes to the anti-inflammatory effect
      of acupuncture in the ovalbumin-induced murine asthma model.
AB  - BACKGROUND: Bronchial asthma is a chronic airway inflammatory disease which has
      three main pathological features: airway hyperresponsiveness (AHR), airway
      remodelling, and chronic inflammation. Acupuncture is known to be an effective
      integrative medical therapy that has been used in the treatment of several
      chronic diseases, including bronchial asthma. The aim of the current study was to
      evaluate the effects of acupuncture on inflammation and regulation of the IL
      33/ST2 pathway in a mouse model of asthma. METHODS: The murine asthma model was
      established by both injection and inhalation of ovalbumin (OVA). Within 24 hours
      of the last OVA challenge, lung function was assessed by measurement of the
      airway resistance (RL) and lung dynamic compliance (Cdyn). Pulmonary tissues were
      collected for the detection of pathological changes and mucus secretion. Serum
      levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-33
      and sST2 (secreted ST2) were detected by ELISA. Th17 cell proportions and counts
      in bronchoalveolar lavage fluid (BALF) were analysed by flow cytometry. RESULTS:
      The results showed that AHR, chronic inflammation and mucus secretion were
      significantly suppressed by acupuncture treatment. RL decreased while Cdyn
      increased after acupuncture treatment. There was an apparent decrease in the
      serum concentrations of certain pro-inflammatory cytokines, such as TNF-alpha, IL
      1beta and IL-33, and an increase in sST2 level compared with untreated asthmatic
      mice. Acupuncture also reduced the CD4 +IL-17A+ cell proportion and counts in
      BALF. CONCLUSION: Acupuncture effectively protects lung function and attenuates
      airway inflammation in the OVA-induced mouse model of asthma, which supports the
      role of acupuncture as a potential therapy in asthma treatment.

PMID- 29581140
TI  - Transmission of a TP53 germline mutation from unaffected male carrier associated
      with pediatric glioblastoma in his child and gestational choriocarcinoma in his
      female partner.
AB  - Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition
      syndrome caused by germline alterations in the tumor suppressor gene TP53 LFS is
      associated with numerous malignancies including astrocytoma. Sanger sequencing
      and chromosomal microarray studies of blood and tumor tissue from a 4-yr-old boy
      with glioblastoma demonstrated a germline TP53 mutation with loss of
      heterozygosity for the short arm of Chromosome 17 as the second inactivating
      event in the tumor. There was no family history of LFS, but the child's mother
      had recently died from metastatic choriocarcinoma after antecedent normal term
      delivery of a then 6-mo-old daughter. The choriocarcinoma contained the same TP53
      mutation detected in the proband and the 6-mo-old daughter was confirmed to be a
      carrier. Unexpectedly, the germline TP53 mutation was found to be inherited from
      the unaffected father. We report here the second genetically confirmed case of
      TP53-mutated choriocarcinoma in the partner of an LFS patient. Based on this case
      and recent literature, female partners of LFS patients may have increased risk of
      choriocarcinoma due to transmission of germline TP53 mutation from male carriers.
      Although the Toronto protocol has established an effective approach to detect
      tumors and improve survival in children and adults with LFS, there is a need to
      expand the current criteria to include surveillance of female partners of LFS
      patients for choriocarcinoma and other gestational trophoblastic disease.
      Recognition of this unique mode of transmission of TP53 mutations should be
      considered in genetic counseling for cancer risk assessment and family planning.

PMID- 29581141
TI  - Risk factors for, and prevention of, shoulder injuries in overhead sports: a
      systematic review with best-evidence synthesis.
AB  - OBJECTIVE: To assess the evidence for risk factors and prevention measures for
      shoulder injuries in overhead sports. DESIGN: Systematic review with best
      evidence synthesis. DATA SOURCES: Medline (Ovid), PubMed (complementary search),
      Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core
      Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017. ELIGIBILITY
      CRITERIA FOR SELECTING STUDIES: Randomised controlled trials, cohort studies and
      case-control studies on risk factors or prevention measures for shoulder injuries
      in overhead sports. The eligible studies were quality assessed using the Scottish
      Intercollegiate Guidelines Network criteria. RESULTS: Of 4778 studies identified,
      38 were eligible for quality review and 17 met the quality criteria to be
      included in the evidence synthesis. One additional quality study presented a
      shoulder injury prevention programme. Most studies focused on baseball, lacrosse
      or volleyball (n=13). The risk factors examined included participation level
      (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external
      workload (n=2). The evidence for all risk factors was limited or conflicting. The
      effect of the prevention programme within the subgroup of uninjured players at
      baseline was modest and possibly lacked statistical power. CONCLUSIONS: All
      investigated potential risk factors for shoulder injury in overhead sports had
      limited evidence, and most were non-modifiable (eg, sex). There is also limited
      evidence for the effect of shoulder injury prevention measures in overhead
      sports. PROSPERO TRIAL REGISTRATION NUMBER: CRD42015026850.

PMID- 29581143
TI  - Physical literacy: why should we embrace this construct?

PMID- 29581142
TI  - Femoroacetabular impingement surgery allows 74% of athletes to return to the same
      competitive level of sports participation but their level of performance remains
      unreported: a systematic review with meta-analysis.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) syndrome is one source of hip pain
      that can limit sport participation among athletes. OBJECTIVE: To summarise the
      return to sport (RTS) rate for athletes after surgery for FAI syndrome. METHODS:
      A computer-assisted search of MEDLINE, the Cumulative Index to Nursing and Allied
      Health Literature (CINAHL) and EMBASE databases was performed using keywords
      related to RTS and RTS at preinjury level (RTSPRE) of competition for FAI
      syndrome. The risk of bias in the included studies was assessed using the
      Methodological Index for Non-Randomized Studies scale. RESULTS: 35 studies (1634
      athletes/1828 hips) qualified for analysis. Based on evidence of limited to
      moderate strength (level 3b to 4 studies), athletes return to sport at preinjury
      level post surgery for FAI syndrome at a rate of only 74% (67%-81%). Only 37% of
      studies reported RTSPRE. The mean time from surgery to RTS was 7.0+/-2.6 months.
      The mean follow-up postsurgery was 28.1+/-15.5 months. Professional athletes
      returned to sport (p=0.0002) (although not the preinjury sport level; p=0.63) at
      a higher rate than collegiate athletes. Only 14% of studies reported on athletic
      presurgery and postsurgery athletic performance, which means it is impossible to
      comment on whether athletes return to their previous level of performance or not.
      No studies reported on the specific criteria used to permit players to return to
      sport. 20% of studies reported on career longevity, 51% reported surgical
      complications and 77% reported on surgical failures. CONCLUSION: There was
      limited to moderate evidence that one in four athletes did not return to their
      previous level of sport participation after surgery for FAI syndrome. Only 37% of
      the included studies clearly distinguished RTS from RTSPRE. Poor outcome
      reporting on athletic performance postsurgery makes it difficult to determine to
      what level of performance these athletes actually perform. Thus, if a player asks
      a surgeon 'Will I get back to my previous level of performance?' there are
      presently little to no published data from which to base an answer. PROSPERO
      REGISTRATION NUMBER: CRD42017072762.

PMID- 29581144
TI  - Chronic exertional compartment syndrome of the deep posterior lower leg.

PMID- 29581145
TI  - The BMJ Awards 2018: Dermatology.

PMID- 29581146
TI  - Inhibition of miR-34a-5p alleviates hypoxia-reoxygenation injury by enhancing
      autophagy in steatotic hepatocytes.
AB  - Hypoxia-reoxygenation (H/R) injury in steatotic hepatocytes has been implicated
      in liver dysfunction after liver transplantation. MicroRNAs (miRs) play important
      roles in regulating several cell biology mechanisms related to H/R injury.
      However, the role of miRs in regulating H/R injury in steatotic hepatocytes is
      still unclear. We established an in vitro model for studying H/R injury in
      steatotic hepatocytes and identified miR-34a-5p as a miR that was substantially
      upregulated in steatotic hepatocytes under H/R challenge. MiR-34a-5p expression
      was modified by transfecting miR-34a-5p mimic and inhibitor into H/R-challenged
      steatotic hepatocytes. We found that inhibition of miR-34a-5p alleviated H/R
      induced apoptosis and promoted post-H/R proliferation in steatotic hepatocytes.
      Whereas, overexpression of miR-34a-5p augmented H/R-induced apoptosis and
      prohibited post-H/R proliferation. By examining autophagy, our data demonstrated
      that miR-34a-5p suppressed autophagy in H/R-challenged steatotic hepatocytes,
      induction of autophagy partially rescued the exaggeration of H/R injury induced
      by miR-34a-5p mimic, while inhibition of autophagy impaired the protection of the
      miR-34a-5p inhibitor against H/R injury. In conclusion, miR-34a-5p is crucial in
      exaggerating H/R injury, likely by suppressing autophagy in steatotic
      hepatocytes. Inhibition of miR-34a may be a promising strategy to protect
      steatotic hepatocytes against H/R-injury.

PMID- 29581147
TI  - Gtgen3A, a novel plant GH3 beta-glucosidase, modulates gentio-oligosaccharide
      metabolism in Gentiana.
AB  - Gentiobiose, a beta-1,6-linked glycosyl-disaccharide, accumulates abundantly in
      Gentianaceae and is involved in aspects of plant development, such as fruits
      ripening and release of bud dormancy. However, the mechanisms regulating the
      amount of gentio-oligosaccharide accumulation in plants remain obscure. The
      present study aimed to identify an enzyme that modulates gentio-oligosaccharide
      amount in gentian (Gentiana triflora). A protein responsible for gentiobiose
      hydrolysis, GtGen3A, was identified by partial purification and its peptide
      sequence analysis. The enzyme had a molecular mass of ~67 kDa without a secretory
      signal peptide sequence. Sequence analysis revealed that GtGen3A could be a beta
      glucosidase member belonging to glycoside hydrolase family 3 (GH3). GtGen3A
      showed a homology to GH3 beta-glucan exohydrolases, ExoI of Hordeum vulgare, and
      ExgI from Zea mays, which preferentially hydrolyzed beta-1,3- and beta-1,4-linked
      oligosaccharides. The purified recombinant GtGen3A (rGtGen3A) produced in
      Escherichia coli showed optimal reaction at pH 6.5 and 20 degrees C. The rGtGen3A
      liberated glucose from beta-1,2-, beta-1,3-, beta-1,4-, and beta-1,6-linked
      oligosaccharides, and showed the highest activity toward gentiotriose among the
      substrates tested. Kinetic analysis also revealed that rGtGen3A preferentially
      hydrolyzed gentiotriose. Virus-induced gene silencing of Gtgen3A in gentian
      plantlets resulted in predominant accumulation of gentiotriose rather than
      gentiobiose. Furthermore, the expression level of Gtgen3A was almost similar to
      the amount of gentiobiose in field-grown gentians. These findings suggest that
      the main function of GtGen3A is the hydrolysis of gentiotriose to gentiobiose,
      and that GtGen3A plays a role in modulating gentiobiose amounts in gentian.

PMID- 29581150
TI  - Environmental cadmium exposure is associated with elevated risk of chronic otitis
      media in adults.
AB  - OBJECTIVES: Chronic otitis media (COM) is caused by an infection of the middle
      ear, although it may also be associated with environmental pollutants. Recent
      reports found that cadmium exposure could be toxic to middle ear cell lines, but
      the role of cadmium in the development of COM in humans has not been examined to
      date. We hypothesised that environmental cadmium exposure was associated with an
      increased risk of COM in the general population. METHODS: We analysed cross
      sectional data for 5331 adults of 20 years of age or above, obtained from the
      Korea National Health and Nutrition Examination Survey 2010-2012. We examined the
      association between blood cadmium levels and COM diagnosed by an
      otolaryngologist. RESULTS: The highest quartile group of cadmium blood
      concentration was associated with an OR of 3.33 (95% CI 1.78 to 7.53) for COM,
      after adjusting for potential confounding factors. Doubling blood cadmium
      concentration resulted in an OR of 1.58 (95% CI 1.19 to 2.08) for COM. These
      associations were robust on sensitivity analyses after excluding current smokers
      and former smokers and after excluding subjects with a potential history of
      occupational exposure to cadmium. CONCLUSIONS: The results of our study suggest
      that environmental cadmium exposure is associated with increased risk of COM, and
      further studies are warranted to understand the pathogenetic mechanism by which
      COM is caused by cadmium exposure.

PMID- 29581148
TI  - Transcriptional regulatory networks underlying gene expression changes in
      Huntington's disease.
AB  - Transcriptional changes occur presymptomatically and throughout Huntington's
      disease (HD), motivating the study of transcriptional regulatory networks (TRNs)
      in HD We reconstructed a genome-scale model for the target genes of 718
      transcription factors (TFs) in the mouse striatum by integrating a model of
      genomic binding sites with transcriptome profiling of striatal tissue from HD
      mouse models. We identified 48 differentially expressed TF-target gene modules
      associated with age- and CAG repeat length-dependent gene expression changes in
      Htt CAG knock-in mouse striatum and replicated many of these associations in
      independent transcriptomic and proteomic datasets. Thirteen of 48 of these
      predicted TF-target gene modules were also differentially expressed in striatal
      tissue from human disease. We experimentally validated a specific model
      prediction that SMAD3 regulates HD-related gene expression changes using
      chromatin immunoprecipitation and deep sequencing (ChIP-seq) of mouse striatum.
      We found CAG repeat length-dependent changes in the genomic occupancy of SMAD3
      and confirmed our model's prediction that many SMAD3 target genes are
      downregulated early in HD.

PMID- 29581149
TI  - High-resolution definition of humoral immune response correlates of effective
      immunity against HIV.
AB  - Defining correlates of immunity by comprehensively interrogating the extensive
      biological diversity in naturally or experimentally protected subjects may
      provide insights critical for guiding the development of effective vaccines and
      antibody-based therapies. We report advances in a humoral immunoprofiling
      approach and its application to elucidate hallmarks of effective HIV-1 viral
      control. Systematic serological analysis for a cohort of HIV-infected subjects
      with varying viral control was conducted using both a high-resolution, high
      throughput biophysical antibody profiling approach, providing unbiased dissection
      of the humoral response, along with functional antibody assays, characterizing
      antibody-directed effector functions such as complement fixation and phagocytosis
      that are central to protective immunity. Profiles of subjects with varying viral
      control were computationally analyzed and modeled in order to deconvolute
      relationships among IgG Fab properties, Fc characteristics, and effector
      functions and to identify humoral correlates of potent antiviral antibody
      directed effector activity and effective viral suppression. The resulting models
      reveal multifaceted and coordinated contributions of polyclonal antibodies to
      diverse antiviral responses, and suggest key biophysical features predictive of
      viral control.

PMID- 29581151
TI  - Getting even more serious about prevention: "social injustice is killing on a
      grand scale".

PMID- 29581152
TI  - New drugs: patient hope or harm?

PMID- 29581153
TI  - AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis.
AB  - Olanzapine (OLZ) is an antipsychotic drug used in the treatment of schizophrenia.
      Although effective in reducing psychoses, OLZ causes acute increases in blood
      glucose. The acute effects of OLZ on hyperglycemia are likely caused by
      reductions in insulin secretion, insulin resistance, and increased hepatic
      glucose production. 5AMP-activated protein kinase (AMPK) is an energy sensor
      activated during exercise that can increase insulin sensitivity and insulin
      independent glucose uptake in muscle. 5-Aminoimidazole-4-carboxamide
      ribonucleoside (AICAR) is a pharmacologic agent that, among other effects, can
      activate AMPK in vivo. Conversely, hypothalamic activation of AMPK has been
      suggested to mediate the hyperglycemic effects of OLZ. The purpose of this
      investigation was to determine whether cotreatment with AICAR could prevent acute
      OLZ-induced hyperglycemia in lean and obese C57BL6/J mice. OLZ (5 mg/kg, i.p.)
      caused rapid increases in blood glucose, a blunted insulin response, and pyruvate
      intolerance, all of which were prevented with AICAR cotreatment in both lean and
      obese mice. AICAR did not affect OLZ-induced changes in whole-body substrate
      oxidation or energy expenditure. Peripheral injection of AICAR, but not OLZ,
      activated AMPK signaling in the hypothalamus. The results of the current study
      provide evidence that AICAR prevents OLZ-induced hyperglycemia, despite
      increasing hypothalamic AMPK signaling. These protective effects were associated
      with the preservation of whole-body insulin action and reductions in markers of
      liver glucose production.

PMID- 29581154
TI  - Sepiapterin Enhances Tumor Radio- and Chemosensitivities by Promoting Vascular
      Normalization.
AB  - Previously, we demonstrated that nitric oxide (NO) synthase (NOS) is uncoupled in
      a wide range of solid tumors and that restoring NOS coupling with the
      tetrahydrobiopterin precursor sepiapterin (SP) inhibits tumor progression.
      Endothelial dysfunction characterizes the poorly functional vasculature of solid
      tumors, and since NO is critical for regulation of endothelial function we asked
      whether SP, by recoupling NOS, improves tumor vasculature structure and function
      enhancing chemotherapeutic delivery and response to radiotherapy. MMTV-neu mice
      with spontaneous breast tumors were treated with SP by oral gavage and evaluated
      by multispectral optoacoustic tomographic analysis of tumor HbO2 and by tissue
      staining for markers of hypoxia, blood perfusion, and markers of endothelial and
      smooth muscle proteins. Recoupling tumor NOS activity results in vascular
      normalization observed as reduced tumor hypoxia, improved tumor percentage of
      HbO2 and perfusion, as well as increased pericyte coverage of tumor blood
      vessels. The normalized vasculature and improved tumor oxygenation led to a
      greater than 2-fold increase in radiation-induced apoptosis compared with
      radiation or SP alone. High-performance liquid chromatography analysis of tumor
      doxorubicin levels showed a greater than 50% increase in doxorubicin uptake and a
      synergistic effect on tumor cell apoptosis. This study highlights for the first
      time the importance of NOS uncoupling and endothelial dysfunction in the
      development of tumor vasculature and presents a new approach for improving the
      tumoricidal efficacies of chemotherapy and radiotherapy.

PMID- 29581155
TI  - Disorders of sex development: timing of diagnosis and management in a single
      large tertiary center.
AB  - BACKGROUND: We describe the phenotypic spectrum and timing of diagnosis and
      management in a large series of patients with disorders of sexual development
      (DSD) treated in a single pediatric tertiary center. METHODS: DSD patients who
      had visited our tertiary center during the survey period (between 2004 and 2014)
      were identified based on an ICD-10 inquiry, and their phenotypic and molecular
      genetic findings were recorded from patient charts. RESULTS: Among the 550 DSD
      patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX
      DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean
      age of 4.7 +/- 5.5 years), Klinefelter syndrome (14.5%, 6.8 +/- 6.2 years) and
      bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX
      DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses
      remained stable over the survey period. After the release of the Nordic consensus
      on the management of undescended testes, the age at surgery for bilateral
      cryptorchidism declined significantly (P < 0.001). CONCLUSIONS: Our results show
      that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD
      diagnoses, are still diagnosed relatively late; (ii) a temporal shift was
      observed in the management of bilateral cryptorchidism, which may favorably
      influence patients' adulthood semen quality and (iii) next-generation sequencing
      methods are not fully employed in the diagnostics of DSD patients.

PMID- 29581156
TI  - Height outcome of the recombinant human growth hormone treatment in Turner
      syndrome: a meta-analysis.
AB  - OBJECTIVE: This study sought to determine the effect of the recombinant human
      growth hormone (rhGH) treatment of Turner syndrome (TS) on height outcome.
      METHODS: We searched in MEDLINE, EMBASE and Cochrane Central Register of
      Controlled Trials and Cochrane Database of Systematic Reviews. A literature
      search identified 640 records. After screening and full-text assessment, 11
      records were included in the systematic review. Methodological quality was
      assessed using the Cochrane Risk of Bias tool. RevMan 5.3 software was used for
      meta-analysis. We also assessed the quality of evidence with the GRADE system.
      RESULTS: Compared with controls, rhGH therapy led to increased final height (MD =
      7.22 cm, 95% CI 5.27-9.18, P < 0.001, I2 = 4%; P = 0.18), height standard
      deviation (HtSDS) (SMD = 1.22, 95% CI 0.88-1.56, P < 0.001, I2 = 49%; P = 0.14)
      and height velocity (HV) (MD 2.68 cm/year; 95% CI 2.34, 3.02; P < 0.001, I2 = 0%;
      P = 0.72). There was a small increase in bone age (SMD 0.32 years; 95% CI 0.1,
      0.54; P = 0.004, I2 = 73%; P = 0.02) after rhGH therapy for 12 months. What is
      more, the rhGH/oxandrolone combination therapy suggested greater final height (MD
      2.46 cm; 95% CI 0.73, 4.18; P = 0.005, I2 = 32%; P = 0.22), increase and faster
      HV (SMD 1.67 cm/year; 95% CI 1.03, 2.31; P < 0.03, I2 = 80%; P < 0.001), with no
      significant increase in HtSDS and bone maturation compared with rhGH therapy
      alone. CONCLUSIONS: For TS patients, rhGH alone or with concomitant use of
      oxandrolone treatment had advantages on final height.

PMID- 29581157
TI  - Regulation of mitochondrial trifunctional protein modulates nonalcoholic fatty
      liver disease in mice.
AB  - Mitochondrial trifunctional protein (MTP) plays a critical role in the oxidation
      of long-chain fatty acids. We previously reported that aging mice (>9 months old)
      heterozygous for an MTP defect (MTP+/-) develop nonalcoholic fatty liver disease
      (NAFLD). We tested whether a high-fat diet (HFD) accelerates NAFLD in young MTP+/
      mice, and whether overexpression of the nicotinamide adenine dinucleotide (NAD+)
      dependent deacetylase sirtuin 3 (SIRT3) deacetylates MTP and improves
      mitochondrial function and NAFLD. Three-month-old WT and MTP+/- mice were fed HFD
      (60% cal fat) for 16 weeks and livers were assessed for fatty acid oxidation
      (FAO) and NAFLD. Compared with WT, MTP+/- mice displayed reduced hepatic SIRT3
      levels and reduced FAO, with increased hepatic steatosis and the inflammatory
      marker CD68. Hepatic overexpression of SIRT3 in HFD-fed MTP+/- mice increased
      hepatic MTP protein levels at the posttranscriptional level. Immunoprecipitation
      of MTP from liver mitochondria followed by Western blot with acetyl-lysine
      antibody showed higher acetylation of MTP in MTP+/- compared with WT mice.
      Overexpression of SIRT3 in MTP+/- mice significantly reduced the acetylation of
      MTP compared with beta-galactosidase controls, increased mitochondrial FAO, and
      reduced hepatic steatosis, CD68, and serum ALT levels. Taken together, our data
      indicate that deacetylation of MTP by SIRT3 improves mitochondrial function and
      rescues NAFLD in MTP+/- mice.

PMID- 29581159
TI  - Long division: summing up Brexit and the NHS.

PMID- 29581158
TI  - Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I
      at Tyr192 and compromises its cardioprotective activity.
AB  - ApoA-I, the main structural and functional protein of HDL particles, is
      cardioprotective, but also highly sensitive to proteolytic cleavage. Here, we
      investigated the effect of cardiac mast cell activation and ensuing chymase
      secretion on apoA-I degradation using isolated rat hearts in the Langendorff
      perfusion system. Cardiac mast cells were activated by injection of compound
      48/80 into the coronary circulation or by low-flow myocardial ischemia, after
      which lipid-free apoA-I was injected and collected in the coronary effluent for
      cleavage analysis. Mast cell activation by 48/80 resulted in apoA-I cleavage at
      sites Tyr192 and Phe229, but hypoxic activation at Tyr192 only. In vitro, the
      proteolytic end-product of apoA-I with either rat or human chymase was the Tyr192
      truncated fragment. This fragment, when compared with intact apoA-I, showed
      reduced ability to promote migration of cultured human coronary artery
      endothelial cells in a wound-healing assay. We propose that C-terminal truncation
      of apoA-I by chymase released from cardiac mast cells during ischemia impairs the
      ability of apoA-I to heal damaged endothelium in the ischemic myocardium.

PMID- 29581160
TI  - Tackling smoking cessation systematically among inpatients with heart disease.

PMID- 29581161
TI  - Smoking abstinence 1 year after acute coronary syndrome: follow-up from a
      randomized controlled trial of varenicline in patients admitted to hospital.
AB  - BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at
      increased risk of reinfarction and death. We previously found use of varenicline
      to increase abstinence 24 weeks after acute coronary syndrome; here we report
      results through 52 weeks. METHODS: The EVITA trial was a multicentre, double
      blind, randomized, placebo-controlled trial of varenicline for smoking cessation
      in patients admitted to hospital with acute coronary syndrome. Participants were
      randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in
      conjunction with low-intensity counselling. Smoking abstinence was assessed via 7
      day recall, with biochemical validation using exhaled carbon monoxide.
      Participants lost to follow-up or withdrawn were assumed to have returned to
      smoking. RESULTS: Among the 302 participants, abstinence declined over the course
      of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome.
      Compared with placebo, point estimates suggest use of varenicline increased point
      prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval
      [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v.
      21.2%, difference 9.9%, 95% CI -0.01% to 19.8%) and reduction in daily cigarette
      smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI -3.1% to
      19.4%). Varenicline and placebo groups had similar occurrence of serious adverse
      events (24.5% v. 21.9%, risk difference 2.7%, 95% CI -7.3% to 12.6%) and major
      adverse cardiovascular events (8.6% v. 9.3%, risk difference -0.7%, 95% CI -7.8%
      to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in
      this high-risk patient population. However, 60% of patients who received
      treatment with varenicline still returned to smoking. Trial registration:
      ClinicalTrials.gov, no. NCT00794573.

PMID- 29581162
TI  - Person-level changes in oxycodone use after the introduction of a tamper
      resistant formulation in Australia.
AB  - BACKGROUND: Australia introduced tamper-resistant controlled-release (CR)
      oxycodone in April 2014. We quantified the impact of the reformulation on
      dispensing, switching and poisonings. METHODS: We performed interrupted time
      series analyses using population-representative national dispensing data from
      2012 to 2016. We measured dispensing of oxycodone CR (>= 10 mg), discontinuation
      of use of strong opioids and switching to other strong opioids after the
      reformulation compared with a historical control period. Similarly, we compared
      calls about intentional opioid poisoning using data from a regional poisons
      information centre. RESULTS: After the reformulation, dispensing decreased for 10
      30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%)
      and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in
      participants less than 65 years of age but was unchanged in people 65 years of
      age or older. Compared with the previous year, discontinuation of use of strong
      opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00),
      but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32
      to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest
      increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI
      2.13 to 8.80). Participants switching after the reformulation were more likely to
      be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40,
      95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone
      taken orally increased immediately after the reformulation (incidence rate ratio
      (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone.
      INTERPRETATION: The reformulation had a greater impact on opioid access patterns
      of people less than 65 years of age who were using higher strengths of oxycodone
      CR. This group has been identified as having an increased risk of problematic
      opioid use and warrants closer monitoring in clinical practice.

PMID- 29581163
TI  - Human granulocytic anaplasmosis acquired from a blacklegged tick in Ontario.

PMID- 29581164
TI  - Low-risk ankle injuries in children.

PMID- 29581165
TI  - Fueling the culture of distrust in physicians.

PMID- 29581166
TI  - Creating the conditions that allow health for all to emerge.

PMID- 29581167
TI  - Most Quebec medical residents show signs of burnout.

PMID- 29581168
TI  - Medical trainees want benefit of doubt when reporting harassment.

PMID- 29581169
TI  - Are provincial medical associations taking physician mental health seriously
      enough?

PMID- 29581170
TI  - Public health in the Anthropocene.

PMID- 29581171
TI  - From white to beige: a new hypothalamic pathway.

PMID- 29581172
TI  - The power of synthetic biology for bioproduction, remediation and pollution
      control: The UN's Sustainable Development Goals will inevitably require the
      application of molecular biology and biotechnology on a global scale.

PMID- 29581174
TI  - Online consulting in general practice: making the move from disruptive innovation
      to mainstream service.

PMID- 29581175
TI  - Making Better CARs for Kids.
AB  - Researchers have found that prior chemotherapy may impair the ability to
      manufacture effective chimeric antigen receptor (CAR) T-cell therapies. In
      addition, they determined that T cells that use fatty-acid pathways for fuel had
      greater potential as CAR T-cell therapies than cells that relied on glycolysis.
      Their conclusions have led to a change in the timing of T-cell collection.

PMID- 29581176
TI  - Identification of Pik3ca Mutation as a Genetic Driver of Prostate Cancer That
      Cooperates with Pten Loss to Accelerate Progression and Castration-Resistant
      Growth.
AB  - Genetic alterations that potentiate PI3K signaling are frequent in prostate
      cancer, yet how different genetic drivers of the PI3K cascade contribute to
      prostate cancer is unclear. Here, we report PIK3CA mutation/amplification
      correlates with poor survival of patients with prostate cancer. To interrogate
      the requirement of different PI3K genetic drivers in prostate cancer, we employed
      a genetic approach to mutate Pik3ca in mouse prostate epithelium. We show
      Pik3caH1047R mutation causes p110alpha-dependent invasive prostate carcinoma in
      vivo Furthermore, we report that PIK3CA mutation and PTEN loss coexist in
      patients with prostate cancer and can cooperate in vivo to accelerate disease
      progression via AKT-mTORC1/2 hyperactivation. Contrasting single mutants that
      slowly acquire castration-resistant prostate cancer (CRPC), concomitant Pik3ca
      mutation and Pten loss caused de novo CRPC. Thus, Pik3ca mutation and Pten
      deletion are not functionally redundant. Our findings indicate that PIK3CA
      mutation is an attractive prognostic indicator for prostate cancer that may
      cooperate with PTEN loss to facilitate CRPC in patients.Significance: We show
      PIK3CA mutation correlates with poor prostate cancer prognosis and causes
      prostate cancer in mice. Moreover, PIK3CA mutation and PTEN loss coexist in
      prostate cancer and can cooperate in vivo to accelerate tumorigenesis and
      facilitate CRPC. Delineating this synergistic relationship may present new
      therapeutic/prognostic approaches to overcome castration/PI3K-AKT-mTORC1/2
      inhibitor resistance. Cancer Discov; 8(6); 764-79. (c)2018 AACR.See related
      commentary by Triscott and Rubin, p. 682This article is highlighted in the In
      This Issue feature, p. 663.

PMID- 29581173
TI  - Structural mechanisms of CFTR function and dysfunction.
AB  - Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) chloride channel
      plays a critical role in regulating transepithelial movement of water and
      electrolyte in exocrine tissues. Malfunction of the channel because of mutations
      of the cftr gene results in CF, the most prevalent lethal genetic disease among
      Caucasians. Recently, the publication of atomic structures of CFTR in two
      distinct conformations provides, for the first time, a clear overview of the
      protein. However, given the highly dynamic nature of the interactions among
      CFTR's various domains, better understanding of the functional significance of
      these structures requires an integration of these new structural insights with
      previously established biochemical/biophysical studies, which is the goal of this
      review.

PMID- 29581177
TI  - RECX Interacts with Mitochondrial RECA to Maintain Mitochondrial Genome
      Stability.
AB  - The chloroplast and mitochondrial genomes are essential for photosynthesis and
      respiration, respectively. RECA and RECG, which are plant-specific homologs of
      the bacterial homologous recombination repair proteins RecA and RecG, maintain
      organelle genome stability by suppressing aberrant recombination between short
      dispersed repeats (SDRs) in the moss Physcomitrella patens In this study, we
      analyzed the plant-specific factor RECX, a homolog of bacterial RecX that
      regulates RecA. RECX fused to GFP colocalized with mitochondrial RECA1 and
      chloroplast RECA2 on mitochondrial and chloroplast nucleoids, respectively.
      Knockout (KO) and overexpression (OEX) of RECX did not alter the P. patens
      morphological phenotype. Analysis of mitochondrial DNA, however, showed that
      products from recombination between SDRs increased significantly in RECX OEX
      mitochondria and modestly in RECX KO mitochondria. By contrast, analysis of
      chloroplast DNA revealed no substantial alteration in the number of products from
      recombination between SDRs in RECX KO and OEX chloroplasts. Yeast two-hybrid
      analysis revealed interactions between RECX and RECA1 and between RECX and RECA2.
      Expression profiles showed a positive correlation between RECX and factors
      maintaining the stability of both organelle genomes and RECA1 Collectively, these
      results suggest that RECX maintains mitochondrial genome stability, likely by
      modulating RECA1 activity, and that the compromised function of RECX induces
      mitochondrial genome instability.

PMID- 29581178
TI  - Rice Morphology Determinant-Mediated Actin Filament Organization Contributes to
      Pollen Tube Growth.
AB  - For successful fertilization in angiosperms, rapid tip growth in pollen tubes
      delivers the male gamete into the ovules. The actin-binding protein-mediated
      organization of the actin cytoskeleton within the pollen tube plays a crucial
      role in this polarized process. However, the mechanism underlying the polarity of
      the actin filament (F-actin) array and behaviors in pollen tube growth remain
      largely unknown. Here, we demonstrate that an actin-organizing protein, Rice
      Morphology Determinant (RMD), a type II formin from rice (Oryza sativa), controls
      pollen tube growth by modulating the polarity and distribution of the F-actin
      array. The rice rmd mutant exhibits abnormal pollen tube growth and a decreased
      germination rate of the pollen grain in vitro and in vivo. The rmd pollen tubes
      display a disorganized F-actin pattern with disrupted apical actin density and
      shank longitudinal cable direction/arrangement, indicating the novel role of RMD
      in F-actin polarity during tip growth. Consistent with this role, RMD localizes
      at the tip of the rice pollen tube, which is essential for pollen tube growth and
      polarity as well as F-actin organization. Furthermore, the direction and
      characteristics of the RMD-guided F-actin array positively regulate the
      deposition of cell wall components and the pattern and velocity of cytoplasmic
      streaming during rice pollen tube growth. Collectively, our results suggest that
      RMD is essential for the spatial regulation of pollen tube growth via modulating
      F-actin organization and array orientation in rice. This work provides insights
      into tip-focused cell growth and polarity.

PMID- 29581179
TI  - Selective Targeting of Mobile mRNAs to Plasmodesmata for Cell-to-Cell Movement.
AB  - Many plant mRNAs move from cell to cell or long distance to execute non-cell
      autonomous functions. These mobile mRNAs traffic through the phloem to regulate
      many developmental processes, but despite the burgeoning discovery of mobile
      mRNAs, little is known about the mechanism underlying the intracellular sorting
      of these mRNAs. Here, we exploited a fluorescence-based mRNA labeling system,
      using the bacteriophage coat protein MS2, fused to GFP (MS2-GFP) and an MS2
      recognition site in the RNA of interest, to visualize the intracellular
      trafficking of mobile mRNAs in living plant cells of Nicotiana benthamiana We
      first improved this system by using the nuclear localization sequence from FD,
      which substantially reduced the fluorescent background of MS2-GFP in the
      cytoplasm. The modified system allowed us to observe the cytoplasmic fluorescent
      foci dependent on MS2-binding sites. Coexpressing the MS2-GFP system with a virus
      movement protein, which is a plasmodesmata (PD)-localized nonspecific RNA-binding
      protein, targeted cytoplasmic fluorescent foci to the PD, suggesting that the
      cytoplasmic fluorescent foci contain mRNA and MS2-GFP. Our ex vivo RNA imaging
      revealed that mobile but not nonmobile mRNAs were selectively targeted to PD.
      Real-time images of intracellular translocation revealed that the translocation
      of mRNA and organelles in the transvacuolar strands may be governed by the same
      mechanism. Our study suggests that PD targeting of mRNA is a selective step in
      determining mRNA cell-to-cell movement of mRNAs.

PMID- 29581180
TI  - Soft X-Ray Imaging of Cellular Carbon and Nitrogen Distributions in Heterocystous
      Cyanobacteria.
AB  - Soft x-ray microscopy (SXM) is a minimally invasive technique for single-cell
      high-resolution imaging as well as the visualization of intracellular
      distributions of light elements such as carbon, nitrogen, and oxygen. We used SXM
      to observe photosynthesis and nitrogen fixation in the filamentous cyanobacterium
      Anabaena sp. PCC 7120, which can form heterocysts during nitrogen starvation.
      Statistical and spectroscopic analyses from SXM images around the K-absorption
      edge of nitrogen revealed a significant difference in the carbon-to-nitrogen
      (C/N) ratio between vegetative cells and heterocysts. Application of this
      analysis to soft x-ray images of Anabaena sp. PCC 7120 revealed inhomogenous C/N
      ratios in the cells. Furthermore, soft x-ray tomography of Anabaena sp. PCC 7120
      revealed differing cellular C/N ratios, indicating different carbon and nitrogen
      distributions between vegetative cells and heterocysts in three dimensions.

PMID- 29581181
TI  - Sports Sponsorships of Food and Nonalcoholic Beverages.
AB  - BACKGROUND: Food and nonalcoholic beverage companies spend millions of dollars on
      professional sports sponsorships, yet this form of marketing is understudied.
      These sponsorships are valuable marketing tools but prompt concerns when
      unhealthy products are associated with popular sports organizations, especially
      those viewed by youth. METHODS: This descriptive study used Nielsen audience data
      to select 10 sports organizations with the most 2-17 year old viewers of 2015
      televised events. Sponsors of these organizations were identified and assigned to
      product categories. We identified advertisements promoting food and/or
      nonalcoholic beverage sponsorships on television, YouTube, and sports
      organization Web sites from 2006 to 2016, and the number of YouTube advertisement
      views. The nutritional quality of advertised products was assessed. RESULTS:
      Youth watched telecasts associated with these sports organizations over 412
      million times. These organizations had 44 food and/or nonalcoholic beverage
      sponsors (18.8% of sponsors), second to automotive sponsors (n = 46). The
      National Football League had the most food and/or nonalcoholic beverage sponsors
      (n = 10), followed by the National Hockey League (n = 7) and Little League (n =
      7). We identified 273 advertisements that featured food and/or nonalcoholic
      beverage products 328 times and product logos 83 times (some advertisements
      showed multiple products). Seventy-six percent (n = 132) of foods had unhealthy
      nutrition scores, and 52.4% (n = 111) of nonalcoholic beverages were sugar
      sweetened. YouTube sponsorship advertisements totaled 195.6 million views.
      CONCLUSIONS: Sports sponsorships are commonly used to market unhealthy food and
      nonalcoholic beverages, exposing millions of consumers to these advertisements.

PMID- 29581182
TI  - Pediatric Hoverboard and Skateboard Injuries.
AB  - OBJECTIVES: To investigate the characteristics of hoverboard injuries compared
      with skateboard injuries in children presenting to US emergency departments
      (EDs). METHODS: Data regarding hoverboard and skateboard injuries in children <18
      years of age were obtained from the National Electronic Injury Surveillance
      System for calendar years 2015 and 2016. Data included demographics, body regions
      injured, and ED disposition. RESULTS: There were an estimated 26 854 hoverboard
      and 121 398 skateboard injuries treated in US EDs between 2015 and 2016. The mean
      and median ages for hoverboard and skateboard injuries were 11 and 13 years,
      respectively. In both groups, boys were more commonly injured. The majority of
      hoverboard injuries occurred at home, whereas skateboard injuries occurred on the
      street. The wrists were the most common injured body part, and fractures were the
      most common diagnosis in both groups. The majority of patients in both groups
      were discharged from the hospital. Approximately 3% of the patients with
      skateboard injuries and hoverboard injuries were admitted to the hospital.
      CONCLUSIONS: The distribution of injuries among hoverboard riders and
      skateboarders was similar. Fractures, contusions, and sprains and/or strains were
      the most common types of injuries in both riders. However, there was a higher
      number of sprains and/or strains in skateboarders when compared with hoverboard
      users. This difference may be attributed to the way users ride these boards.
      Fractures were the most common reason for hospital admission for both toys. By
      elucidating the characteristics of hoverboard injuries, preventive measures can
      be implemented to decrease the incidence of these injuries as well as ED visits.

PMID- 29581183
TI  - How cells sense their own shape - mechanisms to probe cell geometry and their
      implications in cellular organization and function.
AB  - Cells come in a variety of shapes that most often underlie their functions.
      Regulation of cell morphogenesis implies that there are mechanisms for shape
      sensing that still remain poorly appreciated. Global and local cell geometry
      features, such as aspect ratio, size or membrane curvature, may be probed by
      intracellular modules, such as the cytoskeleton, reaction-diffusion systems or
      molecular complexes. In multicellular tissues, cell shape emerges as an important
      means to transduce tissue-inherent chemical and mechanical cues into
      intracellular organization. One emergent paradigm is that cell-shape sensing is
      most often based upon mechanisms of self-organization, rather than determinism.
      Here, we review relevant work that has elucidated some of the core principles of
      how cellular geometry may be conveyed into spatial information to guide
      processes, such as polarity, signaling, morphogenesis and division-plane
      positioning.

PMID- 29581184
TI  - Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage
      impairs trabecularization and mechanical strength of bone.
AB  - The transcription factor GATA2 is required for expansion and differentiation of
      hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs) GATA2 blocks
      adipogenesis, but its biological relevance and underlying genomic events are
      unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs
      binds near genes involved in skeletal system development and co-localizes with
      motifs for FOX and HOX transcription factors, known regulators of skeletal
      development. Ectopic GATA2 blocks osteoblastogenesis by interfering with
      SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases numbers
      and differentiation capacity of bone-derived precursors, resulting in elevated
      bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs
      trabecularization and mechanical strength of bone, involving reduced MSC
      expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast
      numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect
      effects. By regulating bone trabecularization, GATA2 expression in the osteogenic
      lineage may contribute to the anatomical and cellular microenvironment of the HSC
      niche required for hematopoiesis.

PMID- 29581185
TI  - The C-Terminal Extension Unique to the Long Isoform of the Shelterin Component
      TIN2 Enhances Its Interaction with TRF2 in a Phosphorylation- and Dyskeratosis
      Congenita Cluster-Dependent Fashion.
AB  - TIN2 is central to the shelterin complex, linking the telomeric proteins TRF1 and
      TRF2 with TPP1/POT1. Mutations in TINF2, which encodes TIN2, that are found in
      dyskeratosis congenita (DC) result in very short telomeres and cluster in a
      region shared by the two TIN2 isoforms, TIN2S (short) and TIN2L (long). Here we
      show that TIN2L, but not TIN2S, is phosphorylated. TRF2 interacts more with TIN2L
      than TIN2S, and both the DC cluster and phosphorylation promote this enhanced
      interaction. The binding of TIN2L, but not TIN2S, is affected by TRF2-F120, which
      is also required for TRF2's interaction with end processing factors such as
      Apollo. Conversely, TRF1 interacts more with TIN2S than with TIN2L. A DC
      associated mutation further reduces TIN2L-TRF1, but not TIN2S-TRF1, interaction.
      Cells overexpressing TIN2L or phosphomimetic TIN2L are permissive to telomere
      elongation, whereas cells overexpressing TIN2S or phosphodead TIN2L are not.
      Telomere lengths are unchanged in cell lines in which TIN2L expression has been
      eliminated by clustered regularly interspaced short palindromic repeat
      (CRISPR)/Cas9-mediated mutation. These results indicate that TIN2 isoforms are
      biochemically and functionally distinguishable and that shelterin composition
      could be fundamentally altered in patients with TINF2 mutations.

PMID- 29581186
TI  - The phosphatase PTPL1 is required for PTEN-mediated regulation of apical membrane
      size.
AB  - PTEN is a tumor suppressor frequently lost in epithelial malignancies. Part of
      the tumor suppressive properties of PTEN is attributed to its function in cell
      polarization and consequently its role in maintaining epithelial tissue
      integrity. However, surprisingly little is known about the function and
      regulation of PTEN during epithelial cell polarization.We used CRISPR/Cas9
      mediated gene disruption to delete PTEN in intestinal epithelial Ls174T:W4 cells,
      which upon differentiation form a microvilli-covered apical membrane (brush
      border) on a part of the cell cortex, independent of cell-cell junctions. We show
      that loss of PTEN results in the formation of a larger brush border that, in a
      fraction of the cells, even spans the entire plasma membrane, revealing that PTEN
      functions in the regulation of apical membrane size. Depletion of the phosphatase
      PTPL1 resulted in a similar defect. PTPL1 interacts with PTEN, and this
      interaction is necessary for apical membrane enrichment of PTEN. Importantly,
      phosphatase activity of PTPL1 is not required, indicating that PTPL1 functions as
      an anchor protein in this process.Our work thus demonstrates a novel function for
      PTEN during cell polarization in controlling apical membrane size and identifies
      PTPL1 as a critical apical membrane anchor for PTEN in this process.

PMID- 29581187
TI  - RBM4 Modulates Radial Migration via Alternative Splicing of Dab1 during Cortex
      Development.
AB  - The RNA-binding motif 4 (RBM4) protein participates in cell differentiation via
      its role in regulating the expression of tissue-specific or developmentally
      regulated mRNA splice isoforms. RBM4 is expressed in embryonic brain during
      development; it is initially enriched in the ventricular zone/subventricular zone
      and subsequently distributed throughout the cerebral cortex. Rbm4a knockout brain
      exhibited delayed migration of late-born neurons. Using in utero electroporation,
      we confirmed that knockdown of RBM4 impaired cortical neuronal migration. RNA
      immunoprecipitation with high-throughput sequencing identified Disabled-1 (Dab1),
      which encodes a critical reelin signaling adaptor, as a potential target of RBM4.
      Rbm4a knockout embryonic brain showed altered Dab1 isoform ratios. Overexpression
      of RBM4 promoted the inclusion of Dab1 exons 7 and 8 (7/8), whereas its
      antagonist polypyrimidine tract-binding protein 1 (PTBP1) acted in an opposite
      manner. RBM4 directly counteracted the effect of PTBP1 on exon 7/8 selection.
      Finally, we showed that the full-length Dab1, but not exon 7/8-truncated Dab1,
      rescued neuronal migration defects in RBM4-depleted neurons, indicating that RBM4
      plays a role in neuronal migration via modulating the expression of Dab1 splice
      isoforms. Our findings imply that RBM4 is necessary during brain development and
      that its deficiency may lead to developmental brain abnormality.

PMID- 29581188
TI  - New Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A
      Streptococcal Infection.
AB  - Zinc plays an important role in host innate immune function. However, the innate
      immune system also utilizes zinc starvation ("nutritional immunity") to combat
      infections. Here, we investigate the role of zinc import and export in the
      protection of Streptococcus pyogenes (group A Streptococcus; GAS), a Gram
      positive bacterial pathogen responsible for a wide spectrum of human diseases,
      against challenge from host innate immune defense. In order to determine the role
      of GAS zinc import and export during infection, we utilized zinc import
      (DeltaadcA DeltaadcAII) and export (DeltaczcD) deletion mutants in competition
      with the wild type in both in vitro and in vivo virulence models. We demonstrate
      that nutritional immunity is deployed extracellularly, while zinc toxicity is
      utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and
      azurophilic granules in neutrophils contain zinc stores for use against
      intracellular pathogens.

PMID- 29581189
TI  - Identification and Characterization of the Neisseria gonorrhoeae MscS-Like
      Mechanosensitive Channel.
AB  - Mechanosensitive channels are ubiquitous in bacteria and provide an essential
      mechanism to survive sudden exposure to a hypo-osmotic environment by the sensing
      and release of increased turgor pressure. No mechanosensitive channels have thus
      far been identified and characterized for the human-specific bacterial pathogen
      Neisseria gonorrhoeae In this study, we identified and characterized the N.
      gonorrhoeae MscS-like mechanosensitive channel (Ng-MscS). Electrophysiological
      analyses by the patch clamp method showed that Ng-MscS is stretch activated and
      contains pressure-dependent gating properties. Further mutagenesis studies of
      critical residues forming the hydrophobic vapor lock showed that gain-of-function
      mutations in Ng-MscS inhibited bacterial growth. Subsequent analysis of the
      function of Ng-MscS in N. gonorrhoeae by osmotic down-shock assays revealed that
      the survival of Ng-mscS deletion mutants was significantly reduced compared with
      that of wild-type strains, while down-shock survival was restored upon the
      ectopic complementation of mscS Finally, to investigate whether Ng-MscS is
      important for N. gonorrhoeae during infections, competition assays were performed
      by using a murine vaginal tract infection model. Ng-mscS deletion mutants were
      outcompeted by N. gonorrhoeae wild-type strains for colonization and survival in
      this infection model, highlighting that Ng-MscS contributes to in vivo
      colonization and survival. Therefore, Ng-MscS might be a promising target for the
      future development of novel antimicrobials.

PMID- 29581190
TI  - Candida albicans White-Opaque Switching Influences Virulence but Not Mating
      during Oropharyngeal Candidiasis.
AB  - The capacity of Candida albicans to switch reversibly between the white phenotype
      and the opaque phenotype is required for the fungus to mate. It also influences
      virulence during hematogenously disseminated candidiasis. We investigated the
      roles of the mating type loci (MTL) and white-opaque switching in the capacity of
      C. albicans to mate in the oropharynx and cause oropharyngeal candidiasis (OPC).
      When immunosuppressed mice were orally infected with mating-competent opaque a/a
      and alpha/alpha cells either alone or mixed with white cells, no detectable
      mating occurred, indicating that the mating frequency was less than 1.6 * 10-6
      Opaque cells were also highly attenuated in virulence; they either were cleared
      from the oropharynx or switched to the white phenotype during OPC. Although there
      were strain-to-strain differences in the virulence of white cells, they were
      consistently more virulent than opaque cells. In vitro studies indicated that
      relative to white cells, opaque cells had decreased capacity to invade and damage
      oral epithelial cells. The reduced invasion of at least one opaque strain was due
      to reduced surface expression of the Als3 invasin and inability to activate the
      epidermal growth factor receptor, which is required to stimulate the epithelial
      cell endocytic machinery. These results suggest that mating is a rare event
      during OPC because opaque cells have reduced capacity to invade and damage the
      epithelial cells of the oral mucosa.

PMID- 29581191
TI  - Kingella kingae Surface Polysaccharides Promote Resistance to Human Serum and
      Virulence in a Juvenile Rat Model.
AB  - Kingella kingae is a Gram-negative coccobacillus that is increasingly being
      recognized as an important cause of invasive disease in young children. The
      pathogenesis of K. kingae disease begins with colonization of the oropharynx,
      followed by invasion of the bloodstream, survival in the intravascular space, and
      dissemination to distant sites. Recent studies have revealed that K. kingae
      produces a number of surface factors that may contribute to the pathogenic
      process, including a polysaccharide capsule and an exopolysaccharide. In this
      study, we observed that K. kingae was highly resistant to the bactericidal
      effects of human serum complement. Using mutant strains deficient in expression
      of capsule, exopolysaccharide, or both in assays with human serum, we found that
      elimination of both capsule and exopolysaccharide was required for efficient
      binding of IgG, IgM, C4b, and C3b to the bacterial surface and for complement
      mediated killing. Abrogation of the classical complement pathway using EGTA
      treated human serum restored survival to wild-type levels by the mutant lacking
      both capsule and exopolysaccharide, demonstrating that capsule and
      exopolysaccharide promote resistance to the classical complement pathway.
      Consistent with these results, loss of both capsule and exopolysaccharide
      eliminated invasive disease in juvenile rats with an intact complement system but
      not in rats lacking complement. Based on these observations, we conclude that the
      capsule and the exopolysaccharide have important redundant roles in promoting
      survival of K. kingae in human serum. Each of these surface factors is sufficient
      by itself to fully prevent serum opsonin deposition and complement-mediated
      killing of K. kingae, ultimately facilitating intravascular survival and
      promoting K. kingae invasive disease.

PMID- 29581192
TI  - Characterization of Individual Human Antibodies That Bind Pertussis Toxin
      Stimulated by Acellular Immunization.
AB  - Despite high vaccination rates, the incidence of whooping cough has steadily been
      increasing in developing countries for several decades. The current acellular
      pertussis (aP) vaccines all include the major protective antigen pertussis toxin
      (PTx) and are safer, but they appear to be less protective than infection or
      older, whole-cell vaccines. To better understand the attributes of individual
      antibodies stimulated by aP, we isolated plasmablast clones recognizing PTx after
      booster immunization of two donors. Five unique antibody sequences recognizing
      native PTx were recovered and expressed as recombinant human IgG1 antibodies. The
      antibodies all bind different epitopes on the PTx S1 subunit, B oligomer, or S1-B
      subunit interface, and just one clone neutralized PTx in an in vitro assay. To
      better understand the epitopes bound by the nonneutralizing S1-subunit
      antibodies, comprehensive mutagenesis with yeast display provided a detailed map
      of the epitope recognized by antibodies A8 and E12. Residue R76 is required for
      antibody A8 binding and is present on the S1 surface but is only partially
      exposed in the holotoxin, providing a structural explanation for A8's inability
      to neutralize holotoxin. The B-subunit-specific antibody D8 inhibited PTx binding
      to a model receptor and neutralized PTx in vitro as well as in an in vivo
      leukocytosis assay. This is the first study, to our knowledge, to identify
      individual human antibodies stimulated by the acellular pertussis vaccine and
      demonstrates the feasibility of using these approaches to address outstanding
      issues in pertussis vaccinology, including mechanisms of accelerated waning of
      protective immunity despite repeated aP immunization.

PMID- 29581194
TI  - The role of Sca2 and RickA in the dissemination of Rickettsia parkeri in
      Amblyomma maculatum.
AB  - The gram-negative obligate intracellular bacterium Rickettsia parkeri is an
      emerging tick-borne human pathogen. Recently, R. parkeri Sca2 and RickA have been
      implicated in adherence and actin-based motility in vertebrate host cell
      infection models; however, the rickettsial-derived factors essential to tick
      infection are unknown. Using R. parkeri mutants lacking functional Sca2 or RickA
      to compare actin polymerization, replication, and cell-to-cell spread in vitro,
      similar phenotypes in tick and mammalian cells were observed. Specifically, actin
      polymerization in cultured tick cells is controlled by the two separate proteins
      in a time-dependent manner. To assess the role of Sca2 and RickA in dissemination
      in the tick host, Rickettsia-free Amblyomma maculatum, the natural vector of R.
      parkeri, were exposed to the wild-type, R. parkeri rickA::tn, or R. parkeri
      sca2::tn bacteria and individual tick tissues including salivary glands, midguts,
      ovaries, and hemolymph were analyzed at 12 hours and after continued bloodmeal
      acquisition for 3 or 7 days post-exposure. Initially, ticks exposed to wild-type
      R. parkeri had the highest rickettsial load across all organs; however,
      rickettsial loads decreased and wild-type rickettsiae were cleared in the ovaries
      at seven days post-exposure. In contrast, ticks exposed to R. parkeri rickA::tn
      or R. parkeri sca2::tn had comparatively lower rickettsial loads, but bacteria
      persisted in all organs for seven days. These data suggest that, while RickA and
      Sca2 function in actin polymerization in tick cells, the absence of these
      proteins did not change dissemination patterns with the tick vector.

PMID- 29581193
TI  - Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of
      Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and
      Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial
      Infection.
AB  - Cysteamine is an endogenous aminothiol produced in mammalian cells as a
      consequence of coenzyme A metabolism through the activity of the vanin family of
      pantetheinase ectoenzymes. It is known to have a biological role in oxidative
      stress, inflammation, and cell migration. There have been several reports
      demonstrating anti-infective properties targeting viruses, bacteria, and even the
      malarial parasite. We and others have previously described broad-spectrum
      antimicrobial and antibiofilm activities of cysteamine. Here, we go further to
      demonstrate redox-dependent mechanisms of action for the compound and how its
      antimicrobial effects are, at least in part, due to undermining bacterial
      defenses against oxidative and nitrosative challenges. We demonstrate the
      therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in
      mouse models of infection. We also demonstrate potentiation of many different
      classes of antibiotics against a selection of priority antibiotic-resistant
      pathogens, including colistin (often considered an antibiotic of last resort),
      and we discuss how this endogenous antimicrobial component of innate immunity has
      a role in infectious disease that is beginning to be explored and is not yet
      fully understood.

PMID- 29581195
TI  - Serine-Rich Repeat Adhesins Mediate Shear-Enhanced Streptococcal Binding to
      Platelets.
AB  - The binding of bacteria to platelets is thought to be a central event in the
      pathogenesis of infective endocarditis. The serine-rich repeat (SRR)
      glycoproteins of viridans group streptococci have been shown to mediate platelet
      binding in vitro and to contribute to virulence in animal models. However, it is
      not known whether SRR adhesins can mediate streptococcal binding under the high
      fluidic shear stress conditions present on the endocardial surface. We found that
      three streptococcal SRR adhesins (GspB, Hsa, and SrpA) with differing structures
      and sialoglycan binding specificities nevertheless exhibited similar
      biomechanical properties. All three adhesins mediated shear-enhanced
      streptococcal binding to immobilized platelets through the platelet receptor
      GPIbalpha. Shear-enhanced adhesion was manifested in three ways. First, the
      number of circulating streptococci binding via SRR adhesins to immobilized
      platelet receptors peaked at 1 dyn/cm2 Second, bound streptococci switched from
      weak rolling to strong stationary adhesion as shear stress increased to 10
      dyn/cm2 Third, while a few streptococci detached each time the flow was
      increased, the majority of streptococci bound to platelets remained firmly
      attached through 20 to 80 dyn/cm2 (shear levels typical of arteries and the
      endocardium). Thus, all three adhesins mediated shear-enhanced streptococcal
      binding to platelets under the flow conditions found in heart valves. The ability
      of the SRR adhesins to mediate shear-enhanced binding strongly suggests that they
      form catch bonds that are activated by tensile force and provides a mechanism for
      the selective targeting of bacteria to platelet receptors immobilized on the
      endocardial surface.

PMID- 29581196
TI  - Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia
      australis Requires a Functional Complement System.
AB  - The complement system has a well-defined role in deterring blood-borne
      infections. However, complement is not entirely efficacious, as several bacterial
      pathogens, including some obligate intracellular pathogens, have evolved
      mechanisms for resistance. It is presumed that obligate intracellular bacteria
      evade complement attack by residing within a host cell; however, recent studies
      have challenged this presumption. Here, we demonstrate that the complement system
      is activated during infection with the obligate intracellular bacterium
      Rickettsia australis and that genetic ablation of complement increases
      susceptibility to infection. Interaction of Rickettsia australis with serum-borne
      complement leads to activation of the complement cascade, producing three
      effector mechanisms that could negatively influence R. australis. The C9
      dependent membrane attack complex can lead to deposition of a bacteriolytic
      membrane pore on the bacteria, but this system does not contribute to control of
      rickettsial infection. Similarly, complement receptor (CR1/2)-dependent
      opsonophagocytosis may lead to engulfment and killing of the bacteria, but this
      system is also dispensable for immunity. Nevertheless, intact complement is
      essential for naturally acquired and antibody-mediated immunity to Rickettsia
      infection. Comparison of infection in mice lacking the central complement protein
      C3 with infection in their wild-type counterparts demonstrated decreases in gamma
      interferon (IFN-gamma) production, IgG secretion, and spleen hyperplasia in
      animals lacking complement. The correlation between loss of secondary immune
      functions and loss of complement indicates that the proinflammatory signaling
      components of the complement system, and not membrane attack complex or
      opsonophagocytosis, contribute to the immune response to this pathogen.

PMID- 29581197
TI  - Tumor Necrosis Factor Alpha Antagonism Reveals a Gut/Lung Axis That Amplifies
      Regulatory T Cells in a Pulmonary Fungal Infection.
AB  - Tumor necrosis factor (TNF) antagonists are popular therapies for inflammatory
      diseases. These agents enhance the numbers and function of regulatory T cells
      (Tregs), which are important in controlling inflammatory diseases. However,
      elevated Treg levels increase susceptibility to infections, including
      histoplasmosis. We determined the mechanism by which Tregs expand in TNF
      neutralized mice infected with Histoplasma capsulatum Lung CD11c+ CD11b+
      dendritic cells (DCs), but not alveolar macrophages, from H. capsulatum-infected
      mice treated with anti-TNF induced a higher percentage of Tregs than control DCs
      in vitro CD11b+ CD103+ DCs, understood to be unique to the intestines, were
      augmented in lungs with anti-TNF treatment. In the absence of this subset, DCs
      from anti-TNF-treated mice failed to amplify Tregs in vitro CD11b+ CD103+ DCs
      from TNF-neutralized mice displayed higher retinaldehyde dehydrogenase 2 (RALDH2)
      gene expression, and CD11b+ CD103+ RALDH+ DCs exhibited greater enzyme activity.
      To determine if CD11b+ CD103+ DCs migrated from gut to lung, fluorescent beads
      were delivered to the gut via oral gavage, and the lungs were assessed for bead
      containing DCs. Anti-TNF induced migration of CD11b+ CD103+ DCs from the gut to
      the lung that enhanced the generation of Tregs in H. capsulatum-infected mice.
      Therefore, TNF neutralization promotes susceptibility to pulmonary H. capsulatum
      infection by promoting a gut/lung migration of DCs that enhances Tregs.

PMID- 29581198
TI  - Care home services at the vanguard: a qualitative study exploring stakeholder
      views on the development and evaluation of novel, integrated approaches to
      enhancing healthcare in care homes.
AB  - OBJECTIVES: To explore stakeholders' understanding of novel integrated approaches
      to enhancing care in care homes (a care home 'vanguard') and identify priorities
      for evaluation. DESIGN: A qualitative study, using semistructured interviews with
      commissioners and service providers to/within care homes, and third sector
      organisations with thematic analysis. SETTING: A Clinical Commissioning Group
      (CCG) area in England. PARTICIPANTS: Thirty interviewees from care homes, the
      National Health Service (NHS; England) and local authority, third sector (10 care
      home managers, 5 general practitioners, 4 CCG employees, 4 local authority
      employees, 1 national (NHS England) vanguard lead, 2 specialist nurses, 2
      geriatricians, 1 third sector and 1 health manager). RESULTS: Four higher level
      themes emerged from the data: understanding of proposed changes, communication,
      evaluation of outcome measures of success, and trust and complexity. The vision
      for the new programme was shared by stakeholders, with importance attached to
      equitable access to high-quality care. Support for the programme was described as
      being 'the right thing to do', inferring a moral imperative. However, the
      practical implications of key aspects, such as integrated working, were not
      clearly understood and the programme was perceived by some as being imposed, top
      down, from the health service. Barriers and facilitators to change were
      identified across themes of communication, outcomes, trust and complexity.
      Importance was attached to the measurement of intangible aspects of success, such
      as collaboration. Interviewees understood that outcome-based commissioning was
      one element of the new programme, but discussion of their aspirations and
      practices revealed values and beliefs more compatible with a system based on
      trust. CONCLUSIONS: Innovation in service delivery requires organisations to
      adopt common priorities and share responsibility for success. The vanguard
      programme is working to ensure health and local authorities have this commitment,
      but engaging care homes that may feel isolated from the welfare system needs
      sustained dialogue over the longer term. Evaluation of the programme needs to
      measure what is important to stakeholders, and not focus too closely on resource
      consumption.

PMID- 29581199
TI  - Is exposure to ionising radiation associated with childhood cardiac arrhythmia in
      the Russian territories contaminated by the Chernobyl fallout? A cross-sectional
      population-based study.
AB  - OBJECTIVE: To investigate childhood cardiac arrhythmia and chronic exposure to
      caesium-137 (137Cs) resulting from the Chernobyl accident. DESIGN: Prospective
      cross-sectional study using exposed/unexposed design conducted in the Bryansk
      region from May 2009 to May 2013 on children selected on the basis of 137Cs soil
      deposition: control territories ([137Cs]<37 kBq per square metre, where children
      were considered as unexposed) and contaminated territories ([137Cs]>555 kBq per
      square metre, where children were considered as exposed). SETTING: Russian
      territories affected by the Chernobyl fallout (Bryansk region). PARTICIPANTS:
      This cross-sectional study included 18 152 children aged 2-18 years and living in
      the Bryansk region (Russia). MAIN OUTCOME MEASURES: All children received three
      medical examinations (ECG, echocardiography and 137Cs whole-body activity
      measurement) and some of them were given with a 24-hour Holter monitoring and
      blood tests. RESULTS: Cardiac arrhythmia was diagnosed in 1172 children living in
      contaminated territories and 1354 children living in control territories. The
      crude prevalence estimated to 13.3% in contaminated territories was significantly
      lower than in control territories with 15.2% over the period 2009-2013 (P<0.001).
      Considering 137Cs whole-body burden as exposure, cardiac arrhythmia was found in
      449 contaminated children and 2077 uncontaminated children, corresponding to an
      estimated crude prevalence of 14.5% and 14.2%, respectively, which does not
      differ significantly (P=0.74). Also, we investigated the association between
      territory, exposure to 137Cs and cardiac arrhythmia: the adjusted OR was not
      significant (0.90 with 95% CI 0.81 to 1.00; P=0.06) for the territory. For 137Cs
      whole-body burden, the ORs close to 1 did not reach statistical significance (P
      for trend=0.97). CONCLUSION: This study does not observe an association between
      cardiac arrhythmia and 137Cs deposition levels in the Bryansk region exposed to
      Chernobyl fallout. The suspected increase of cardiac arrhythmia in children
      exposed to Chernobyl fallout is not confirmed.

PMID- 29581200
TI  - Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult
      pneumonia in Italy: a case-control study in a 2-year prospective cohort.
AB  - OBJECTIVES: Current strategies to prevent adult pneumococcal disease have been
      recently reviewed in Italy. We did a postlicensure study to estimate the direct
      vaccine effectiveness (VE) of the 13-valent pneumococcal conjugate vaccine
      (PCV13) against adult pneumococcal community-acquired pneumonia (pCAP). STUDY
      DESIGN: Between 2013 and 2015, a 2-year prospective cohort study of adults with
      CAP was conducted in the Apulia region of Italy where the average vaccine uptake
      of PCV13 was 32% among adults >=65 years. The test-negative design was used to
      estimate VE against all episodes of confirmed pCAP and vaccine-type (VT)-CAP. VE
      in a subgroup of patients managed in the community was also estimated using a
      matched case-control design. VE was calculated as one minus the OR times 100%.
      RESULTS: The overall VE of PCV13 was 33.2% (95% CI -106.6% to 82%) against pCAP
      irrespective of serotype and 38.1% (95% CI -131.9% to 89%) against VT-CAP in the
      cohort of adults >=65 years. The VE was 42.3% (95% CI -244.1% to 94.7%) against
      VT-CAP in the age group at higher vaccine uptake. For the subgroup of cases
      managed in the community, the overall VE against disease due to any pneumococcal
      strain was 88.1% (95% CI 4.2% to 98.5%) and 91.7% (95% CI 13.1% to 99.2%) when we
      controlled for underlying conditions. CONCLUSIONS: Although our results are non
      significant, PCV13 promises to be effective against all confirmed pCAP already
      with modest levels of uptake in the population of adults >=65 years of age.
      Larger studies are needed to confirm the direct vaccine benefits.

PMID- 29581201
TI  - Voices from low-income and middle-income countries: a systematic review protocol
      of primary healthcare interventions within public health systems addressing
      intimate partner violence against women.
AB  - INTRODUCTION: Intimate partner violence (IPV) considerably harms the health,
      safety and well-being of women. In response, public health systems around the
      globe have been gradually implementing strategies. In particular, low-income and
      middle-income countries (LMIC) have been developing innovative interventions in
      primary healthcare (PHC) addressing the problem. This paper describes a protocol
      for a systematic review of studies addressing the impacts and outcomes of PHC
      centre interventions addressing IPV against women from LMIC. METHODS AND
      ANALYSIS: A systematic search for studies will be conducted in African Index
      Medicus, Africa Portal Digital Library, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), Embase, Index Medicus for the Southeast Asia Region,
      IndMed, Latin American and Caribbean Health Science Literature Database (LILACS),
      Medecins Sans Frontieres, MEDLINE, Minority Health and Health Equity Archive,
      ProQuest, PsycINFO, Scientific Electronic Library Online, (SciELO) and Social
      Policy and Practice. Studies will be in English, Spanish and Portuguese,
      published between 2007 and 2017, addressing IPV against women from LMIC, whose
      data quantitatively report on the impacts and outcomes for survivors and/or
      workers and/or public health systems preintervention and postintervention. Two
      trilingual reviewers will independently screen for study eligibility and data
      extraction, and a librarian will cross-check for compliance. Risk of bias and
      quality assessment of studies will be measured according to: (1) the Cochrane
      Collaboration's tool for assessing risk of bias for randomised controlled trials
      and (2) the Methodological Index for Non-Randomised Studies (MINORS). Data will
      be analysed and summarised using meta-analysis and narrative description of the
      evidence across studies. This systematic review will be reported according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      Protocols(PRISMA P) guidelines. ETHICS AND DISSEMINATION: This systematic review
      will be based on published studies, thus not requiring ethical approval. Findings
      will be presented in conferences and published in a peer-reviewed journal.
      PROSPERO REGISTRATION NUMBER: CRD42017069261.

PMID- 29581202
TI  - Real-world effects of medications for chronic obstructive pulmonary disease:
      protocol for a UK population-based non-interventional cohort study with
      validation against randomised trial results.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive
      disease affecting 3 million people in the UK, in which patients exhibit airflow
      obstruction that is not fully reversible. COPD treatment guidelines are largely
      informed by randomised controlled trial results, but it is unclear if these
      findings apply to large patient populations not studied in trials. Non
      interventional studies could be used to study patient groups excluded from
      trials, but the use of these studies to estimate treatment effectiveness is in
      its infancy. In this study, we will use individual trial data to validate non
      interventional methods for assessing COPD treatment effectiveness, before
      applying these methods to the analysis of treatment effectiveness within people
      excluded from, or under-represented in COPD trials. METHODS AND ANALYSIS: Using
      individual patient data from the landmark COPD Towards a Revolution in COPD
      Health (TORCH) trial and validated methods for detecting COPD and exacerbations
      in routinely collected primary care data, we will assemble a cohort in the UK
      Clinical Practice Research Datalink (selecting people between 1 January 2004 and
      1 January 2017) with similar characteristics to TORCH participants and test
      whether non-interventional data can generate comparable results to trials, using
      cohort methodology with propensity score techniques to adjust for potential
      confounding. We will then use the methodological template we have developed to
      determine risks and benefits of COPD treatments in people excluded from TORCH.
      Outcomes are pneumonia, COPD exacerbation, mortality and time to treatment
      change. Groups to be studied include the elderly (>80 years), people with
      substantial comorbidity, people with and without underlying cardiovascular
      disease and people with mild COPD. ETHICS AND DISSEMINATION: Ethical approval has
      been granted by the London School of Hygiene & Tropical Medicine Ethics Committee
      (Ref: 11997). The study has been approved by the Independent Scientific Advisory
      Committee of the UK Medicines and Healthcare Products Regulatory Agency (protocol
      no. 17_114R). An application to use the TORCH trial data made to
      clinicalstudydatarequest.com has been approved. In addition to scientific
      publications, dissemination methods will be developed based on discussions with
      patient groups with COPD.

PMID- 29581203
TI  - Glycaemic control in type 2 diabetes patients and its predictors: a retrospective
      database study at a tertiary care diabetes centre in Ningbo, China.
AB  - OBJECTIVES: The objectives of the study were to assess glycaemic control in
      patients with type 2 diabetes (T2DM) at a tertiary care diabetes centre in
      Ningbo, China and to determine factors that independently predict their glycaemic
      control. DESIGN: Retrospective cross-sectional study using an existing database,
      the Diabetes Information Management System. SETTING: Tertiary care diabetes
      centre in Ningbo, China. PARTICIPANTS: The study included adult patients with
      T2DM, registered and received treatment at the diabetes centre for at least six
      consecutive months. The study inclusion criteria were satisfied by 1387 patients,
      from 1 July 2012 to 30 June 2017. PRIMARY OUTCOME MEASURE: Glycaemic control
      (poor was defined as glycated haemoglobin (HbA1c)>=7% or fasting blood glucose
      (FBG)>7.0 mmol/L). RESULTS: In terms of HbA1c and FBG, the 5-year period
      prevalence of poor glycaemic control was 50.3% and 57.3%, respectively. In terms
      of HbA1c and FBG, the odds of poor glycaemic control increased with the duration
      of T2DM (>1 to 2 years: OR 1.84, 95% CI 1.06 to 3.19; >2 to 4 years: 3.32, 1.88
      to 5.85 and >4 years: 5.98, 4.09 to 8.75 and >1 to 2 years: 2.10, 1.22 to 3.62;
      >2 to 4 years: 2.48, 1.42 to 4.34 and >4 years: 3.34, 2.32 to 4.80) and were
      higher in patients residing in rural areas (1.68, 1.24 to 2.28 and 1.42, 1.06 to
      1.91), with hyperlipidaemia (1.57, 1.12 to 2.19 and 1.68, 1.21 to 2.33), on diet,
      physical activity and oral hypoglycaemic drug (OHD) as part of their T2DM
      therapeutic regimen (1.80, 1.01 to 3.23 and 2.40, 1.36 to 4.26) and on diet,
      physical activity, OHD and insulin (2.47, 1.38 to 4.41 and 2.78, 1.58 to 4.92),
      respectively. CONCLUSIONS: More than half of patients with T2DM at the diabetes
      centre in Ningbo, China have poor glycaemic control, and the predictors of
      glycaemic control were identified. The study findings could be taken into
      consideration in future interventional studies aimed at improving glycaemic
      control in these patients.

PMID- 29581204
TI  - A cost of illness study of hypoglycaemic events in insulin-treated diabetes in
      the Netherlands.
AB  - OBJECTIVES: Patients with diabetes mellitus are at a risk for hypoglycaemia.
      Besides the burden of hypoglycaemia for patients, hypoglycaemia poses an economic
      burden to society. The aim of this study was to calculate the per patient
      societal costs of hypoglycaemia among patients with type1 diabetes (T1DM) and
      type 2 diabetes (T2DM) on insulin therapy in the Netherlands. METHODS: To
      calculate the costs of hypoglycaemia, data from the Global Hypoglycaemia
      Assessment Tool (HAT) study were used. Dutch patients were selected from the HAT
      study database and data regarding healthcare resource use, informal care use and
      productivity losses were combined with Dutch unit costs to calculate the per
      patient 4-week costs of patients experiencing hypoglycaemia. Besides these 4-week
      costs, costs per hypoglycaemic event were calculated by dividing the study
      population total 4-week costs by the total number of events in this period.
      RESULTS: Mean 4-week total costs of hypoglycaemia amounted to ?163 (SD, ?870) in
      T1DM and ?134 (SD, ?364) in T2DM. While productivity costs were the most
      important cost driver of hypoglycaemia in patients with T1DM (accounting for 72%
      of the total costs), costs of hypoglycaemia in patients with T2DM were almost
      entirely driven by costs within the healthcare sector (accounting for 98% of the
      total costs). Mean costs of a severe hypoglycaemic event were ?828 and ?508 in
      T1DM and T2DM, respectively, whereas mean costs of a non-severe event were almost
      zero. CONCLUSIONS: This study showed that the economic burden of severe
      hypoglycaemia is substantial. The prevention of hypoglycaemia could therefore not
      only reduce the burden for patients, but also the economic burden to society.

PMID- 29581205
TI  - A cross-sectional study of all clinicians' conflict of interest disclosures to
      NHS hospital employers in England 2015-2016.
AB  - OBJECTIVE: We set out to document how NHS trusts in the UK record and share
      disclosures of conflict of interest by their employees. DESIGN: Cross-sectional
      study of responses to a Freedom of Information Act request for Gifts and
      Hospitality Registers. SETTING: NHS Trusts (secondary/tertiary care
      organisations) in England. PARTICIPANTS: 236 Trusts were contacted, of which 217
      responded. MAIN OUTCOME MEASURES: We assessed all disclosures for completeness
      and openness, scoring them for achieving each of five measures of transparency.
      RESULTS: 185 Trusts (78%) provided a register. 71 Trusts did not respond within
      the 28 day time limit required by the FoIA. Most COI registers were incomplete by
      design, and did not contain the information necessary to assess conflicts of
      interest. 126/185 (68%) did not record the names of recipients. 47/185 (25%) did
      not record the cash value of the gift or hospitality. Only 31/185 registers (16%)
      contained the names of recipients, the names of donors, and the cash amounts
      received. 18/185 (10%) contained none of: recipient name, donor name, and cash
      amount. Only 15 Trusts had their disclosure register publicly available online
      (6%). We generated a transparency index assessing whether each Trust met the
      following criteria: responded on time; provided a register; had a register with
      fields identifying donor, recipient, and cash amount; provided a register in a
      format that allowed further analysis; and had their register publicly available
      online. Mean attainment was 1.9/5; no NHS trust met all five criteria.
      CONCLUSION: Overall, recording of employees' conflicts of interest by NHS trusts
      is poor. None of the NHS Trusts in England met all transparency criteria. 19 did
      not respond to our FoIA requests, 51 did not provide a Gifts and Hospitality
      Register and only 31 of the registers provided contained enough information to
      assess employees' conflicts of interest. Despite obligations on healthcare
      professionals to disclose conflicts of interest, and on organisations to record
      these, the current system for logging and tracking such disclosures is not
      functioning adequately. We propose a simple national template for reporting
      conflicts of interest, modelled on the US 'Sunshine Act'.

PMID- 29581206
TI  - Validation of an algorithm to identify heart failure hospitalisations in patients
      with diabetes within the veterans health administration.
AB  - OBJECTIVES: We aimed to validate an algorithm using both primary discharge
      diagnosis (International Classification of Diseases Ninth Revision (ICD-9)) and
      diagnosis-related group (DRG) codes to identify hospitalisations due to
      decompensated heart failure (HF) in a population of patients with diabetes within
      the Veterans Health Administration (VHA) system. DESIGN: Validation study.
      SETTING: Veterans Health Administration-Tennessee Valley Healthcare System
      PARTICIPANTS: We identified and reviewed a stratified, random sample of
      hospitalisations between 2001 and 2012 within a single VHA healthcare system of
      adults who received regular VHA care and were initiated on an antidiabetic
      medication between 2001 and 2008. We sampled 500 hospitalisations; 400
      hospitalisations that fulfilled algorithm criteria, 100 that did not. Of these,
      497 had adequate information for inclusion. The mean patient age was 66.1 years
      (SD 11.4). Majority of patients were male (98.8%); 75% were white and 20% were
      black. PRIMARY AND SECONDARY OUTCOME MEASURES: To determine if a hospitalisation
      was due to HF, we performed chart abstraction using Framingham criteria as the
      referent standard. We calculated the positive predictive value (PPV), negative
      predictive value (NPV), sensitivity and specificity for the overall algorithm and
      each component (primary diagnosis code (ICD-9), DRG code or both). RESULTS: The
      algorithm had a PPV of 89.7% (95% CI 86.8 to 92.7), NPV of 93.9% (89.1 to 98.6),
      sensitivity of 45.1% (25.1 to 65.1) and specificity of 99.4% (99.2 to 99.6). The
      PPV was highest for hospitalisations that fulfilled both the ICD-9 and DRG
      algorithm criteria (92.1% (89.1 to 95.1)) and lowest for hospitalisations that
      fulfilled only DRG algorithm criteria (62.5% (28.4 to 96.6)). CONCLUSIONS: Our
      algorithm, which included primary discharge diagnosis and DRG codes, demonstrated
      excellent PPV for identification of hospitalisations due to decompensated HF
      among patients with diabetes in the VHA system.

PMID- 29581207
TI  - Cross-sectional associations of objectively assessed neighbourhood attributes
      with depressive symptoms in older adults of an ultra-dense urban environment: the
      Hong Kong ALECS study.
AB  - OBJECTIVES: This study aimed to examine the associations between objectively
      assessed neighbourhood environmental attributes and depressive symptoms in Hong
      Kong Chinese older adults and the moderating effects of neighbourhood
      environmental attributes on the associations between living arrangements and
      depressive symptoms. DESIGN: Cross-sectional observational study. SETTING: Hong
      Kong. PARTICIPANTS: 909 Hong Kong Chinese community dwellers aged 65+ years
      residing in preselected areas stratified by walkability and socioeconomic status.
      EXPOSURE AND OUTCOME MEASURES: Attributes of participants' neighbourhood
      environment were objectively assessed using geographic information systems and
      environmental audits. Depressive symptoms were measured using the Geriatric
      Depression Scale. RESULTS: Overall, pedestrian infrastructure (OR=1.025;
      P=0.008), connectivity (OR=1.039; P=0.002) and prevalence of public transport
      stops (OR=1.056; P=0.012) were positively associated with the odds of reporting
      depressive symptoms. Older adults living alone were at higher risk of reporting
      any depressive symptoms than those living with others (OR=1.497; P=0.039). This
      association was moderated by neighbourhood crowdedness, perceptible pollution,
      access to destinations and presence of people. Residing in neighbourhoods with
      lower levels of these attributes was associated with increased deleterious
      effects of living alone. Living in neighbourhoods with lower public transport
      density also increased the deleterious effects of living alone on the number of
      depressive symptoms. Those living alone and residing in neighbourhoods with
      higher levels of connectivity tended to report more depressive symptoms than
      their counterparts. CONCLUSIONS: The level of access to destinations and social
      networks across Hong Kong may be sufficiently high to reduce the risk of
      depressive symptoms in older adults. Yet, exposure to extreme levels of public
      transport density and associated traffic volumes may increase the risk of
      depressive symptoms. The provision of good access to a variety of destinations,
      public transport and public open spaces for socialising in the neighbourhood may
      help reduce the risk of depressive symptoms in older adults who live alone.

PMID- 29581208
TI  - Omega-3 polyunsaturated fatty acid supplementation for improving peripheral nerve
      health: protocol for a systematic review.
AB  - INTRODUCTION: Damage to peripheral nerves occurs in a variety of health
      conditions. Preserving nerve integrity, to prevent progressive nerve damage,
      remains a clinical challenge. Omega-3 polyunsaturated fatty acids (PUFAs) are
      implicated in the development and maintenance of healthy nerves and may be
      beneficial for promoting peripheral nerve health. The aim of this systematic
      review is to assess the effects of oral omega-3 PUFA supplementation on
      peripheral nerve integrity, including both subjective and objective measures of
      peripheral nerve structure and/or function. METHODS AND ANALYSIS: A systematic
      review of randomised controlled trials that have evaluated the effects of omega-3
      PUFA supplementation on peripheral nerve assessments will be conducted.
      Comprehensive electronic database searches will be performed in Ovid MEDLINE,
      Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US National
      Institutes of Health Clinical Trials Registry and the WHO International Clinical
      Trials Registry Platform. The title, abstract and keywords of identified articles
      will be assessed for eligibility by two reviewers. Full-text articles will be
      obtained for all studies judged as eligible or potentially eligible; these
      studies will be independently assessed by two reviewers to determine eligibility.
      Disagreements will be resolved by consensus. Risk of bias assessment will be
      performed using the Cochrane Collaboration risk of bias tool to appraise the
      quality of included studies. If clinically meaningful, and there are a sufficient
      number of eligible studies, a meta-analysis will be conducted and a summary of
      findings table will be provided. ETHICS AND DISSEMINATION: This is a systematic
      review that will involve the analysis of previously published data, and therefore
      ethics approval is not required. A manuscript reporting the results of this
      systematic review will be published in a peer-reviewed journal and may also be
      presented at relevant scientific conferences. PROSPERO REGISTRATION NUMBER:
      CRD42018086297.

PMID- 29581209
TI  - Index coronary angiography use in Manitoba, Canada: a population-level
      descriptive analysis of First Nations and non-First Nations recipients.
AB  - OBJECTIVES: To investigate recipient characteristics and rates of index
      angiography among First Nations (FN) and non-FN populations in Manitoba, Canada.
      SETTING: Population-based, secondary analysis of provincial administrative health
      data. PARTICIPANTS: All adults 18 years or older who received an index angiogram
      between 2000/2001 and 2008/2009. PRIMARY AND SECONDARY OUTCOME MEASURES: (1)
      Descriptive statistics for age, sex, income quintile by rural and urban residency
      and Charlson Comorbidity Index for FN and non-FN recipients. (2) Annual index
      angiogram rates for FN and non-FN populations and among those rates of 'urgent'
      angiograms based on acute myocardial infarction (AMI)-related hospitalisations
      during the previous 7 days. (3) Proportions of people who did not receive an
      angiogram in the 20 years preceding an ischaemic heart disease (IHD) diagnosis or
      a cardiovascular death; stratified by age (<65 or >=65 years old). RESULTS: FN
      recipients were younger (56.3vs63.8 years; p<0.0001) and had higher Charlson
      Comorbidity scores (1.32vs0.78; p<0.001). During all years examined, index
      angiography rates were lower among FN people (2.67vs3.33 per 1000 population per
      year; p<0.001) with no notable temporal trends. Among the index angiogram
      recipients, a higher proportion was associated with an AMI-related
      hospitalisation in the FN group (28.8%vs25.0%; p<0.01) and in both groups rates
      significantly increased over time. FN people who died from cardiovascular disease
      or were older (65+years old) diagnosed with IHD were more likely to have received
      an angiogram in the preceding 20-30 years (17.8%vs12.5%; p<0.01 and 50.9%vs49.5%;
      p<0.03, respectively). FN people diagnosed with IHD who were under the age of 65
      were less likely to have received an angiogram (47.8%vs53.1%; p<0.01)
      CONCLUSIONS: Index angiogram use differences are suggested between FN and non-FN
      populations, which may contribute to reported IHD disparities. Investigating
      factors driving these rates will determine any association between ethnicity and
      angiography services.

PMID- 29581210
TI  - A systematic assessment of Cochrane reviews and systematic reviews published in
      high-impact medical journals related to cancer.
AB  - OBJECTIVE: To compare cancer-related systematic reviews (SRs) published in the
      Cochrane Database of SRs (CDSR) and high-impact journals, with respect to type,
      content, quality and citation rates. DESIGN: Methodological SR with assessment
      and comparison of SRs and meta-analyses. Two authors independently assessed
      methodological quality using an Assessment of Multiple Systematic Reviews
      (AMSTAR)-based extraction form. Both authors independently screened search
      results, extracted content-relevant characteristics and retrieved citation
      numbers of the included reviews using the Clarivate Analytics Web of Science
      database. DATA SOURCES: Cancer-related SRs were retrieved from the CDSR, as well
      as from the 10 journals which publish oncological SRs and had the highest impact
      factors, using a comprehensive search in both the CDSR and MEDLINE. ELIGIBILITY
      CRITERIA FOR SELECTING STUDIES: We included all cancer-related SRs and meta
      analyses published from January 2011 to May 2016. Methodological SRs were
      excluded. RESULTS: We included 346 applicable Cochrane reviews and 215 SRs from
      high-impact journals. Cochrane reviews consistently met more individual AMSTAR
      criteria, notably with regard to an a priori design (risk ratio (RR) 3.89; 95% CI
      3.10 to 4.88), inclusion of the grey literature and trial registries (RR 3.52;
      95% CI 2.84 to 4.37) in their searches, and the reporting of excluded studies (RR
      8.80; 95% CI 6.06 to 12.78). Cochrane reviews were less likely to address
      questions of prognosis (RR 0.04; 95% CI 0.02 to 0.09), use individual patient
      data (RR 0.03; 95% CI 0.01 to 0.09) or be based on non-randomised controlled
      trials (RR 0.04; 95% CI 0.02 to 0.09). Citation rates of Cochrane reviews were
      notably lower than those for high-impact journals (Cochrane reviews: mean number
      of citations 6.52 (range 0-143); high-impact journal SRs: 74.45 (0-652)).
      CONCLUSIONS: When comparing cancer-related SRs published in the CDSR versus those
      published in high-impact medical journals, Cochrane reviews were consistently of
      higher methodological quality, but cited less frequently.

PMID- 29581211
TI  - Effects of vaccines in patients with sickle cell disease: a systematic review
      protocol.
AB  - INTRODUCTION: Sickle cell disease (SCD) is an inherited haematological disorder
      caused by a single point mutation (Glub6Val) that promotes polymerisation of
      haemoglobin S and sickling of erythrocytes. Inflammation, haemolysis,
      microvascular obstruction and organ damage characterise the highly variable
      clinical expression of SCD. People with SCD are at increased risk of severe
      infections, hence the need for vaccination against common disease-causing
      organisms in this population. We aim to review the evidence on the efficacy and
      safety of vaccines in people with SCD. METHODS AND ANALYSIS: The present
      systematic review will examine the current data as indexed in PubMed, CENTRAL,
      EMBASE and EBSCOHost. We will consult Strategic Advisory Group of Experts
      practice statements, conference abstracts, reference lists of relevant articles,
      WHO ICTRP trial registry and experts in the field. Two authors will independently
      screen search outputs, select studies, extract data and assess risk of bias;
      resolving discrepancies by discussion and consensus between the two authors or
      arbitration by a third author when necessary. We will perform a meta-analysis for
      clinically homogenous studies. Evidence from clinically diverse studies will be
      aggregated using narrative synthesis of the findings. In either case, we will use
      the GRADE approach to assess the strength of the available evidence. ETHICS AND
      DISSEMINATION: The study draws on data that are readily available in the public
      domain, hence no formal ethical review and approval is required. The findings of
      this review will be disseminated through conference presentations and a
      publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER:
      CRD42018084051.

PMID- 29581212
TI  - Study protocol for a self-controlled cluster randomised trial of the Alert
      Program to improve self-regulation and executive function in Australian
      Aboriginal children with fetal alcohol spectrum disorder.
AB  - INTRODUCTION: While research highlights the benefits of early diagnosis and
      intervention for children with fetal alcohol spectrum disorders (FASD), there are
      limited data documenting effective interventions for Australian children living
      in remote communities. METHODS AND ANALYSIS: This self-controlled cluster
      randomised trial is evaluating the effectiveness of an 8-week Alert Program
      school curriculum for improving self-regulation and executive function in
      children living in remote Australian Aboriginal communities. Children in grades 1
      6 attending any of the eight participating schools across the Fitzroy Valley in
      remote North-West Australia (N ~ 363) were invited to participate. Each school
      was assigned to one of four clusters with clusters randomly assigned to receive
      the intervention at one of four time points. Clusters two, three and four had
      extended control conditions where students received regular schooling before
      later receiving the intervention. Trained classroom teachers delivered the Alert
      Program to students in discrete, weekly, 1-hour lessons. Student outcomes were
      assessed at three time points. For the intervention condition, data collection
      occurred 2 weeks immediately before and after the intervention, with a follow-up
      8 weeks later. For control conditions in clusters two to four, the control data
      collection matched that of the data collection for the intervention condition in
      the preceding cluster. The primary outcome is change in self-regulation. FASD
      diagnoses will be determined via medical record review after the completion of
      data collection. The results will be analysed using generalised linear mixed
      modelling and reported in accordance with Consolidated Standards of Reporting
      Trials (CONSORT) guidelines. ETHICS AND DISSEMINATION: Ethical approval was
      obtained from the University of Western Australia (WA) (RA/4/1/7234), WA
      Aboriginal Health Ethics Committee (601) and WA Country Health Service (2015:04).
      The Kimberley Aboriginal Health Planning Forum Research Sub-Committee and WA
      Department of Education also provided approval. The results will be disseminated
      through peer-reviewed journals, conference presentations, the media and at
      forums. TRIAL REGISTRATION NUMBER: ACTRN12615000733572; Pre-results.

PMID- 29581213
TI  - Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in
      Senescence-Accelerated Mice P1.
AB  - Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by
      shortened lifespan and early signs of senescence. Klotho is an aging-suppressor
      gene. The purpose of this study is to investigate whether in vivo expression of
      secreted klotho (Skl) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1
      mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious
      fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of
      Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte
      chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80,
      and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation.
      An increase in expression of alpha-smooth muscle actin (myofibroblast marker),
      transforming growth factorbeta-1, and scleraxis (a transcription factor of
      collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting
      that accelerated aging is associated with myofibroblast transition and collagen
      gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA
      for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl
      of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and
      myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve
      disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic
      valve disease in SAMP1 mice is associated with a decrease in serum klotho leading
      to inflammation, including macrophage infiltration and transforming growth
      factorbeta-1/scleraxis-driven myofibroblast differentiation in aortic valves.
      Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl
      cDNA effectively suppresses inflammation and myofibroblastic transition and
      attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for
      fibrotic aortic valve disease.

PMID- 29581214
TI  - Effect of Lowering Diastolic Pressure in Patients With and Without Cardiovascular
      Disease: Analysis of the SPRINT (Systolic Blood Pressure Intervention Trial).
AB  - Systolic and diastolic blood pressure thresholds, below which cardiovascular
      events increase, are widely debated. Using data from the SPRINT (Systolic Blood
      Pressure Intervention Trial), we evaluated the relation between systolic and
      diastolic pressure and cardiovascular events among 1519 participants with or 7574
      without prior cardiovascular disease. Using Cox regression, we examined the
      composite risk of myocardial infarction, other acute coronary syndrome, stroke,
      heart failure, or cardiovascular death, and follow-up systolic and diastolic
      pressure were analyzed as time-dependent covariates for a median of 3.1 years.
      Models were adjusted for age, sex, baseline systolic pressure, body mass index,
      10-year Framingham risk score, and estimated glomerular filtration rate. A J
      shaped relationship with diastolic pressure was observed in both treatment arms
      in patients with or without cardiovascular disease (P nonlinearity<=0.002). When
      diastolic pressure fell <55 mm Hg, the hazards were at least 25% higher relative
      to 70 mm Hg (P=0.29). The hazard ratios (95% CI) of diastolic pressure <55 mm Hg
      versus 55 to 90 mm Hg were 1.68 (1.16-2.43), P value 0.006 and 1.52 (0.99-2.34),
      P value 0.06 in patients without and with prior cardiovascular disease,
      respectively. After adjusting for follow-up diastolic pressure, follow-up
      systolic pressure was not associated with the outcome in those without prior
      cardiovascular disease (P=0.64). In those with cardiovascular disease, adjusting
      for diastolic pressure, follow-up systolic pressure was associated with the risk
      in the intensive arm (hazard ratio per 10 mm Hg decrease, 0.86; 95% CI, 0.75
      0.99; P interaction=0.02). Although the observed J-shaped relationship may be
      because of reverse causality in the SPRINT population, we advise caution in
      aggressively lowering diastolic pressure.

PMID- 29581215
TI  - Understanding Angiotensin II Type 1 Receptor Signaling in Vascular
      Pathophysiology.

PMID- 29581217
TI  - Tuning orb spider glycoprotein glue performance to habitat humidity.
AB  - Orb-weaving spiders use adhesive threads to delay the escape of insects from
      their webs until the spiders can locate and subdue the insects. These viscous
      threads are spun as paired flagelliform axial fibers coated by a cylinder of
      solution derived from the aggregate glands. As low molecular mass compounds
      (LMMCs) in the aggregate solution attract atmospheric moisture, the enlarging
      cylinder becomes unstable and divides into droplets. Within each droplet an
      adhesive glycoprotein core condenses. The plasticity and axial line extensibility
      of the glycoproteins are maintained by hygroscopic LMMCs. These compounds cause
      droplet volume to track changes in humidity and glycoprotein viscosity to vary
      approximately 1000-fold over the course of a day. Natural selection has tuned the
      performance of glycoprotein cores to the humidity of a species' foraging
      environment by altering the composition of its LMMCs. Thus, species from low
      humidity habits have more hygroscopic threads than those from humid forests.
      However, at their respective foraging humidities, these species' glycoproteins
      have remarkably similar viscosities, ensuring optimal droplet adhesion by
      balancing glycoprotein adhesion and cohesion. Optimal viscosity is also essential
      for integrating the adhesion force of multiple droplets. As force is transferred
      to a thread's support line, extending droplets draw it into a parabolic
      configuration, implementing a suspension bridge mechanism that sums the adhesive
      force generated over the thread span. Thus, viscous capture threads extend an orb
      spider's phenotype as a highly integrated complex of large proteins and small
      molecules that function as a self-assembling, highly tuned, environmentally
      responsive, adhesive biomaterial. Understanding the synergistic role of chemistry
      and design in spider adhesives, particularly the ability to stick in wet
      conditions, provides insight in designing synthetic adhesives for biomedical
      applications.

PMID- 29581216
TI  - The Receptor-Like Cytoplasmic Kinase STRK1 Phosphorylates and Activates CatC,
      Thereby Regulating H2O2 Homeostasis and Improving Salt Tolerance in Rice.
AB  - Salt stress can significantly affect plant growth and agricultural productivity.
      Receptor-like kinases (RLKs) are believed to play essential roles in plant
      growth, development, and responses to abiotic stresses. Here, we identify a
      receptor-like cytoplasmic kinase, salt tolerance receptor-like cytoplasmic kinase
      1 (STRK1), from rice (Oryza sativa) that positively regulates salt and oxidative
      stress tolerance. Our results show that STRK1 anchors and interacts with CatC at
      the plasma membrane via palmitoylation. CatC is phosphorylated mainly at Tyr-210
      and is activated by STRK1. The phosphorylation mimic form CatCY210D exhibits
      higher catalase activity both in vitro and in planta, and salt stress enhances
      STRK1-mediated tyrosine phosphorylation on CatC. Compared with wild-type plants,
      STRK1-overexpressing plants exhibited higher catalase activity and lower
      accumulation of H2O2 as well as higher tolerance to salt and oxidative stress.
      Our findings demonstrate that STRK1 improves salt and oxidative tolerance by
      phosphorylating and activating CatC and thereby regulating H2O2 homeostasis.
      Moreover, overexpression of STRK1 in rice not only improved growth at the
      seedling stage but also markedly limited the grain yield loss under salt stress
      conditions. Together, these results offer an opportunity to improve rice grain
      yield under salt stress.

PMID- 29581219
TI  - Prognostic Performance of Heart Rate Recovery on an Exercise Test in a Primary
      Prevention Population.
AB  - BACKGROUND: Heart rate (HR) recovery has been investigated in specific patient
      cohorts, but there is less information about the role of HR recovery in general
      populations. We investigated whether HR recovery has long-term prognostic
      significance in primary prevention. METHODS AND RESULTS: Exercise tests performed
      between 1993 and 2010 on patients aged 30 to 79 years without cardiovascular
      disease were included. Mortality was determined from Mayo Clinic records and
      Minnesota Death Index. Total, cardiovascular, and non-cardiovascular mortality
      was reported according to HR recovery <13 bpm using Cox regression. 19 551
      patients were included, 6756 women (35%), age 51+/-10 years. There were 1271
      deaths over follow-up of 12+/-5 years. HR recovery declined after age 60, and was
      also lower according to diabetes mellitus, hypertension, obesity, current
      smoking, and poor cardiorespiratory fitness but not sex or beta-blockers.
      Adjusting for these factors, abnormal HR recovery was a significant predictor of
      total (hazard ratio [95% confidence interval]=1.56 [1.384-1.77]), cardiovascular
      (1.95 [1.57-2.42]), and non-cardiovascular death (1.41 [1.22-1.64]). Hazard
      ratios for cardiovascular death according to abnormal HR recovery were
      significant in all age groups (30-59, 60-69, 70-79), in both sexes, in patients
      with and without hypertension, obesity, and diabetes mellitus, but not in
      patients taking beta-blockers, current smokers, and patients with normal
      cardiorespiratory fitness. CONCLUSIONS: HR recovery is a powerful prognostic
      factor predicting total, cardiovascular, and non-cardiovascular death in a
      primary prevention cohort. It performs consistently well according to sex, age,
      obesity, hypertension, and diabetes mellitus but shows diminished utility in
      patients taking beta-blockers, current smokers, and patients with normal
      cardiorespiratory fitness.

PMID- 29581218
TI  - RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial
      Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) has been suggested to protect
      against certain forms of organ injury after cardiac surgery. Previously, we
      reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart
      Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients
      receiving either RIPC or sham-RIPC. METHODS AND RESULTS: In this follow-up paper,
      we present 1-year follow-up of the composite primary end point and its individual
      components (all-cause mortality, myocardial infarction, stroke and acute renal
      failure), in a sub-group of patients, intraoperative myocardial dysfunction
      assessed by transesophageal echocardiography and the incidence of postoperative
      neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither
      showed any beneficial effect on the 1-year composite primary end point (RIPC
      versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause
      mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke
      [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved
      intraoperative myocardial dysfunction or incidence of postoperative
      neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients)
      and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively.
      CONCLUSIONS: Similar to our main study, RIPC had no effect on intraoperative
      myocardial dysfunction, neurocognitive function and long-term outcome in cardiac
      surgery patients undergoing propofol anesthesia. CLINICAL TRIAL REGISTRATION:
      URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

PMID- 29581220
TI  - Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline
      Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients
      With Metabolic Syndrome.
AB  - BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular
      disease via conversion of the dietary compounds choline and carnitine to the
      atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet
      was associated with decreased plasma TMAO levels and nearly absent TMAO
      production on carnitine challenge. METHODS AND RESULTS: We performed a double
      blind randomized controlled pilot study in which 20 male metabolic syndrome
      patients were randomized to single lean vegan-donor or autologous fecal
      microbiota transplantation. At baseline and 2 weeks thereafter, we determined the
      ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and
      unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both
      isotope-labeled precursor nutrients), and fecal samples were collected for
      analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography scans of the abdominal aorta, as well as ex vivo
      peripheral blood mononuclear cell cytokine production assays, were performed. At
      baseline, fecal microbiota composition differed significantly between vegans and
      metabolic syndrome patients. With vegan-donor fecal microbiota transplantation,
      intestinal microbiota composition in metabolic syndrome patients, as monitored by
      global fecal microbial community structure, changed toward a vegan profile in
      some of the patients; however, no functional effects from vegan-donor fecal
      microbiota transplantation were seen on TMAO production, abdominal aortic 18F
      fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood
      mononuclear cells. CONCLUSIONS: Single lean vegan-donor fecal microbiota
      transplantation in metabolic syndrome patients resulted in detectable changes in
      intestinal microbiota composition but failed to elicit changes in TMAO production
      capacity or parameters related to vascular inflammation. CLINICAL TRIAL
      REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR 4338.

PMID- 29581221
TI  - Impact of Type 2 Myocardial Infarction (MI) on Hospital-Level MI Outcomes:
      Implications for Quality and Public Reporting.
AB  - BACKGROUND: The International Classification of Diseases (ICD) coding system does
      not recognize type 2 myocardial infarction (MI) as a separate entity; therefore,
      patients with type 2 MI continue to be categorized under the general umbrella of
      non-ST-segment-elevation myocardial infarction (NSTEMI). We aim to evaluate the
      impact of type 2 MI on hospital-level NSTEMI metrics and discuss the implications
      for quality and public reporting. METHODS AND RESULTS: We conducted a single
      center retrospective analysis of 1318 patients discharged with a diagnosis of
      NSTEMI between July 2013 and October 2014. The Third Universal Definition was
      used to define type 1 and type 2 MI. Weighted Kaplan-Meier curves were used to
      analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI
      criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI.
      Patients with type 2 MI were older, were more likely to have chronic kidney
      disease, and had lower peak troponin levels. Compared with type 1 MI patients,
      those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P<0.0001)
      and were more likely to die from noncardiovascular causes (71.7% versus 25.0%,
      P<0.0001). Despite weighting for patient characteristics and discharge
      medications, patients with type 2 MI had higher mortality at both 30 days (risk
      ratio: 3.63; 95% confidence interval, 1.67-7.88) and 1 year (risk ratio: 1.98;
      95% confidence interval, 1.44-2.73) after discharge. Type 2 MI was also
      associated with a lower 30-day cardiovascular-related readmission (risk ratio:
      0.49; 95% confidence interval, 0.12-2.06). CONCLUSIONS: NSTEMI metrics are
      significantly affected by type 2 MI patients. Type 2 MI patients have distinct
      etiologies, are managed differently, and have higher mortality compared with
      patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2
      MI data from NSTEMI quality metrics.

PMID- 29581222
TI  - Device Therapies Among Patients Receiving Primary Prevention Implantable
      Cardioverter-Defibrillators in the Cardiovascular Research Network.
AB  - BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs)
      reduce mortality in selected patients with left ventricular systolic dysfunction
      by delivering therapies (antitachycardia pacing or shocks) to terminate
      potentially lethal arrhythmias; inappropriate therapies also occur. We assessed
      device therapies among adults receiving primary prevention ICDs in 7 healthcare
      systems. METHODS AND RESULTS: We linked medical record data, adjudicated device
      therapies, and the National Cardiovascular Data Registry ICD Registry. Survival
      analysis evaluated therapy probability and predictors after ICD implant from 2006
      to 2009, with attention to Centers for Medicare and Medicaid Services Coverage
      With Evidence Development subgroups: left ventricular ejection fraction, 31% to
      35%; nonischemic cardiomyopathy <9 months' duration; and New York Heart
      Association class IV heart failure with cardiac resynchronization therapy
      defibrillator. Among 2540 patients, 35% were <65 years old, 26% were women, and
      59% were white. During 27 (median) months, 738 (29%) received >=1 therapy. Three
      year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate
      therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence
      interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with
      atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among
      patients >=65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and
      in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46
      0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence
      Development analysis, inappropriate therapy was less common with cardiac
      resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55;
      95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for
      Medicare and Medicaid Services Coverage With Evidence Development subgroups.
      CONCLUSIONS: In this community cohort of primary prevention patients receiving
      ICD, therapy delivery varied across demographic and clinical characteristics, but
      did not differ meaningfully for Centers for Medicare and Medicaid Services
      Coverage With Evidence Development subgroups.

PMID- 29581223
TI  - Beneficial Pleiotropic Antidepressive Effects of Cardiovascular Disease Risk
      Factor Interventions in the Metabolic Syndrome.
AB  - BACKGROUND: Although the increased prevalence and severity of clinical depression
      and elevated cardiovascular disease risk represent 2 vexing public health issues,
      the growing awareness of their combined presentation compounds the challenge. The
      obese Zucker rat, a model of the metabolic syndrome, spontaneously develops
      significant depressive symptoms in parallel with the progression of the metabolic
      syndrome and, thus, represents a compelling model for study. The primary
      objective was to assess the impact on both cardiovascular outcomes, specifically
      vascular structure and function, and depressive symptoms in obese Zucker rats
      after aggressive treatment for cardiovascular disease risk factors with long-term
      exercise or targeted pharmacological interventions. METHODS AND RESULTS: We
      chronically treated obese Zucker rats with clinically relevant interventions
      against cardiovascular disease risk factors to determine impacts on vascular
      outcomes and depressive symptom severity. While most of the interventions
      (chronic exercise, anti-hypertensive, the interventions (long-term exercise,
      antihypertensive, antidyslipidemia, and antidiabetic) were differentially
      effective at improving vascular outcomes, only those that also resulted in a
      significant improvement to oxidant stress, inflammation, arachidonic acid
      metabolism (prostacyclin versus thromboxane A2), and their associated sequelae
      were effective at also blunting depressive symptom severity. Using multivariable
      analyses, discrimination between the effectiveness of treatment groups to
      maintain behavioral outcomes appeared to be dependent on breaking the cycle of
      inflammation and oxidant stress, with the associated outcomes of improving
      endothelial metabolism and both cerebral and peripheral vascular structure and
      function. CONCLUSIONS: This initial study provides a compelling framework from
      which to further interrogate the links between cardiovascular disease risk
      factors and depressive symptoms and suggests mechanistic links and potentially
      effective avenues for intervention.

PMID- 29581224
TI  - Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early
      Stages of Heart Failure in Mice.
AB  - BACKGROUND: Although advanced heart failure (HF) is a clinically documented risk
      factor for vascular cognitive impairment, the occurrence and pathomechanisms of
      vascular cognitive impairment in early stages of HF are equivocal. Here, we
      characterize vascular cognitive impairment in the early stages of HF development
      and assess whether cerebral hypoperfusion or prothrombotic conditions are
      involved. METHODS AND RESULTS: Tgalphaq*44 mice with slowly developing isolated
      HF triggered by cardiomyocyte-specific overexpression of G-alphaq*44 protein were
      studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left
      ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction
      (with preserved ejection fraction); and left ventricle diastolic/systolic
      dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old
      Tgalphaq*44 mice, behavioral and cognitive impairment was identified with
      compromised blood-brain barrier permeability, most significantly in brain cortex,
      that was associated with myelin sheet loss and changes in astrocytes and
      microglia. Brain endothelial cells displayed increased E-selectin
      immunoreactivity, which was accompanied by increased amyloid-beta1-42
      accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG
      immunoreactivity). Resting cerebral blood flow measured by magnetic resonance
      imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow
      regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month
      old Tgalphaq*44 mice, but it was not associated with increased platelet-dependent
      thrombogenicity. CONCLUSIONS: We report for the first time that vascular
      cognitive impairment is already present in the early stage of HF development,
      even before left ventricle systolic dysfunction. The underlying pathomechanism,
      independent of brain hypoperfusion, involves preceding platelet hyperreactivity
      and brain endothelium inflammatory activation.

PMID- 29581225
TI  - Prognostic Value of Serial N-Terminal Pro-B-Type Natriuretic Peptide Measurements
      in Adults With Congenital Heart Disease.
AB  - BACKGROUND: A single NT-proBNP (N-terminal pro-B-type natriuretic peptide)
      measurement is a strong prognostic factor in adult congenital heart disease. This
      study investigates NT-proBNP profiles within patients with adult congenital heart
      disease and relates these to cardiovascular events. METHODS AND RESULTS: In this
      prospective cohort, 602 patients with adult congenital heart disease were
      enrolled at the outpatient clinic (years 2011-2013). NT-proBNP was measured at
      study inclusion in 595 patients (median age 33 [IQR 25-41] years, 58% male, 90%
      NYHA I) and at subsequent annual visits. The primary end point was defined as
      death, heart failure, hospitalization, arrhythmia, thromboembolic event, or
      cardiac intervention; the secondary end point as death or heart failure. Repeated
      measurements were analyzed using linear mixed models and joint models. During a
      median follow-up of 4.4 [IQR 3.8-4.8] years, a total of 2424 repeated
      measurements were collected. Average NT-proBNP increase was 2.9 pmol/L the year
      before the primary end point (n=199, 34%) and 18.2 pmol/L before the secondary
      end point (n=58, 10%), compared with 0.3 pmol/L in patients who remained end
      point-free (P-value for difference in slope 0.006 and <0.001, respectively). In
      patients with elevated baseline NT-proBNP (>14 pmol/L, n=315, 53%), repeated
      measurements were associated with the primary end point (HR per 2-fold higher
      value 2.08; 95% CI 1.31-3.87; P<0.001) and secondary end point (HR 2.47; 95% CI
      1.13-5.70; P=0.017), when adjusted for the baseline measurement. CONCLUSIONS: NT
      proBNP increased before the occurrence of events, especially in patients who died
      or developed heart failure. Serial NT-proBNP measurements could be of additional
      prognostic value in the annual follow-up of patients with adult congenitive heart
      disease with an elevated NT-proBNP.

PMID- 29581226
TI  - Cause-specific mortality in Swedish males diagnosed with non-psychotic mental
      disorders in late adolescence: a prospective population-based study.
AB  - BACKGROUND: While risk of premature death is most pronounced among persons with
      severe mental illness, also milder conditions are associated with increased all
      cause mortality. We examined non-psychotic mental (NPM) disorders and specific
      causes of natural death in a cohort of late adolescent men followed for up to 46
      years. METHODS: Prospective cohort study of Swedish males (n=1 784 626) who took
      part in structured conscription interviews 1968-2005. 74 525 men were diagnosed
      with NPM disorders at or prior to conscription. Median follow-up time was 26
      years. HRs for cause-specific mortality were calculated using Cox proportional
      hazards models. RESULTS: Risks in fully adjusted models were particularly
      elevated for death by infectious diseases (depressive and neurotic/adjustment
      disorders (HR 2.07; 95% CI 1.60 to 2.67), personality disorders (HR 2.90; 95% CI
      1.96 to 4.28) and alcohol-related and other substance use disorders (HR 9.02; 95%
      CI 6.63 to 12.27)) as well as by gastrointestinal causes (depressive and
      neurotic/adjustment disorders (HR 1.64; 95% CI 1.42 to 1.89), personality
      disorders (HR 2.77; 95% CI 2.27 to 3.38) and alcohol-related/substance use
      disorders (HR 4.41; 95% CI 3.59 to 5.42)). CONCLUSION: Young men diagnosed with
      NPM disorders had a long-term increased mortality risk, in particular due to
      infectious and gastrointestinal conditions. These findings highlight the
      importance of early preventive actions for adolescents with mental illness.

PMID- 29581227
TI  - Clarity in research frameworks for studying 'health selective migration'.

PMID- 29581228
TI  - Socioeconomic inequalities in child vaccination in low/middle-income countries:
      what accounts for the differences?
AB  - BACKGROUND: Socioeconomic inequalities in child vaccination continue to be a
      global public health concern. This study aimed to measure and identify factors
      associated with socioeconomic inequalities in full immunisation coverage against
      the four core vaccine-preventable diseases (ie, bacille Calmette-Guerin,
      diphtheria-tetanus-pertussis (three doses), polio (three doses) and measles
      vaccines) in 46 low/middle-income countries. METHODS: The most recent nationally
      representative samples of children (aged 10-59 months, n=372 499) collected
      through the Demographic Health Surveys were used to measure vaccination rates.
      The concentration index (C) was used to quantify socioeconomic inequalities in
      vaccination coverage. Furthermore, meta-regression analyses were used to
      determine factors affecting socioeconomic inequalities in vaccination coverage
      across countries. RESULTS: Results suggested that immunisation coverage was pro
      rich in most countries (median C=0.161, IQR 0.131). Gambia (C=-0.146, 95% CI 
      0.223 to -0.069), Namibia (C=-0.093, 95% CI -0.145 to -0.041) and Kyrgyz Republic
      (C=-0.227, 95% CI -0.304 to -0.15) were the only countries where children who
      belong to higher socioeconomic status group were less likely to receive all the
      four core vaccines than their lower socioeconomic status counterparts. Meta
      regression analyses suggested that, across countries, the concentration of
      antenatal care visits among wealthier mothers was positively associated with the
      concentration of vaccination coverage among wealthier children
      (coefficient=0.606, 95% CI 0.301 to 0.911). CONCLUSIONS: Pro-rich distribution of
      child vaccination in most low/middle-income countries remains an important public
      health policy concern. Policies aimed to improve antenatal care visits among
      mothers in lower socioeconomic groups may mitigate socioeconomic inequalities in
      vaccination coverage in low/middle-income countries.

PMID- 29581229
TI  - Low level of knowledge of heart attack symptoms and inappropriate anticipated
      treatment-seeking behaviour among older Chinese: a cross-sectional survey.
AB  - BACKGROUND: Prehospital delay of acute myocardial infarction (AMI) is common
      globally, and Hong Kong-home of a rapidly ageing Chinese population-is not an
      exception. Seeking emergency medical care promptly is important for patients.
      Treatment-seeking behaviours have been shown to be associated with knowledge of
      AMI symptoms and specific cultural beliefs. This study aimed to assess the level
      of knowledge of AMI symptoms and expected treatment-seeking behaviour among older
      Chinese in Hong Kong. METHODS: A cross-sectional population-based survey was
      conducted at the Elderly Health Centres in Hong Kong from March to September
      2016. Face-to-face interviews were conducted with a structured questionnaire
      based on previous studies and local adaptations. RESULTS: Among 1804 people aged
      65 years and above who completed the questionnaire, chest pain (80.2%),
      palpitations (75.8%) and fainting (71.9%) were the major symptoms recognised as
      AMI related. Meanwhile, stomach ache (46.9%), coughing (45.4%) and neck pain
      (40.8%) were recognised as not AMI related. The mean expected discomfort
      intensity during AMI onset was 7.7 out of 10 (SD=2.1). Regarding the expected
      treatment-seeking behaviour, seeking non-emergent medical care was the most
      popular action when AMI symptoms emerged during the day, without chest pain or
      with lower discomfort intensity, whereas calling an ambulance was the most common
      option when AMI symptoms emerged at night or with high discomfort intensity.
      CONCLUSIONS: To minimise delays in seeking treatment, future health education
      should focus on increasing the public knowledge of AMI symptoms and the need to
      call an ambulance during an emergency.

PMID- 29581230
TI  - Association between circulating leptin levels and multiple sclerosis: a
      systematic review and meta-analysis.
AB  - AIM: Leptin, synthesised by adipocytes, has been identified as a hormone that can
      influence inflammatory activity. Several studies have investigated leptin levels
      in patients with multiple sclerosis (MS), but the results are not consistent.
      This study aims to derive a more precise evaluation on the relationship between
      circulating leptin levels and MS. DESIGN: A comprehensive literature searched up
      to July 2017 was conducted to evaluate the association of circulating leptin
      levels and MS. The random-effect model was applied to calculate pooled
      standardised mean difference (SMD) and its 95% CI. MAIN OUTCOME MEASURES:
      Circulating leptin levels of patients with MS and healthy controls. RESULTS: Of
      2155 studies identified, 33 met eligibility criteria and 9 studies with 645
      patients with MS and 586 controls were finally included in the meta-analysis.
      Meta-analysis revealed that, compared with the healthy control group, the MS
      group had significantly higher plasma/serum leptin levels, with the SMD of 0.70%
      and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of
      patients with MS were associated with region, age, study sample size, measurement
      type, gender and blood sample type. CONCLUSION: Overall, our study suggests that
      patients with MS have a significantly higher leptin level than in healthy
      controls. Further mechanism studies and longitudinal large cohort studies are
      still needed to further reveal the role of leptin in the pathogenesis of MS.

PMID- 29581231
TI  - Intestinal mucin activates human dendritic cells and IL-8 production in a glycan
      specific manner.
AB  - Cross-talk between different components of the intestinal barrier and the immune
      system may be important in maintaining gut homeostasis. A crucial part of the gut
      barrier is the mucus layer, a cross-linked gel on top of the intestinal
      epithelium that consists predominantly of the mucin glycoprotein MUC2. However,
      whether the mucin layer actively regulates intestinal immune cell responses is
      not clear. Because recent evidence suggests that intestinal dendritic cells (DCs)
      may be regulated by the mucus layer, we purified intestinal mucin, incubated it
      with human DCs, and determined the functional effects. Here we show that
      expression of the chemokine IL-8 and co-stimulatory DC markers CD86 and CD83 are
      significantly up-regulated on human DCs in the presence of intestinal mucins.
      Additionally, mucin-exposed DCs promoted neutrophil migration in an IL-8
      dependent manner. The stimulatory effects of mucins on DCs were not due to mucin
      sample contaminants such as lipopolysaccharide, DNA, or contaminant proteins.
      Instead, mucin glycans are important for the pro-inflammatory effects on DCs.
      Thus, intestinal mucins are capable of inducing important pro-inflammatory
      functions in DCs, which could be important in driving inflammatory responses upon
      intestinal barrier damage.

PMID- 29581232
TI  - Distinct cargo-specific response landscapes underpin the complex and nuanced role
      of galectin-glycan interactions in clathrin-independent endocytosis.
AB  - Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a
      defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting
      from the outside, could be a part of that endocytic machinery. We show that the
      perturbation of global cellular patterns of protein glycosylation by modulation
      of metabolic flux affects CIE. Interestingly, these changes in glycosylation had
      cargo-specific effects. For example, in HeLa cells, GlcNAc treatment, which
      increases glycan branching, increased major histocompatibility complex class I
      (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule
      (CD59). The effects of knocking down the expression of galectin 3, a carbohydrate
      binding protein and an important player in galectin-glycan interactions, were
      also cargo-specific and stimulated CD59 uptake. By contrast, inhibition of all
      galectin-glycan interactions by lactose inhibited CIE of both MHCI and CD59. None
      of these treatments affected clathrin-mediated endocytosis, implying that
      glycosylation changes specifically affect CIE. We also found that the galectin
      lattice tailors membrane fluidity and cell spreading. Furthermore, changes in
      membrane dynamics mediated by the galectin lattice affected macropinocytosis, an
      altered form of CIE, in HT1080 cells. Our results suggest that glycans play an
      important and nuanced role in CIE, with each cargo being affected uniquely by
      alterations in galectin and glycan profiles and their interactions. We conclude
      that galectin-driven effects exist on a continuum from stimulatory to inhibitory,
      with distinct CIE cargo proteins having unique response landscapes and with
      different cell types starting at different positions on these conceptual
      landscapes.

PMID- 29581233
TI  - Kinetics and structural features of dimeric glutamine-dependent bacterial NAD+
      synthetases suggest evolutionary adaptation to available metabolites.
AB  - NADH (NAD+) and its reduced form NADH serve as cofactors for a variety of
      oxidoreductases that participate in many metabolic pathways. NAD+ also is used as
      substrate by ADP-ribosyl transferases and by sirtuins. NAD+ biosynthesis is one
      of the most fundamental biochemical pathways in nature, and the ubiquitous NAD+
      synthetase (NadE) catalyzes the final step in this biosynthetic route. Two
      different classes of NadE have been described to date: dimeric single-domain
      ammonium-dependent NadENH3 and octameric glutamine-dependent NadEGln, and the
      presence of multiple NadE isoforms is relatively common in prokaryotes. Here, we
      identified a novel dimeric group of NadEGln in bacteria. Substrate preferences
      and structural analyses suggested that dimeric NadEGln enzymes may constitute
      evolutionary intermediates between dimeric NadENH3 and octameric NadEGln The
      characterization of additional NadE isoforms in the diazotrophic bacterium
      Azospirillum brasilense along with the determination of intracellular glutamine
      levels in response to an ammonium shock led us to propose a model in which these
      different NadE isoforms became active accordingly to the availability of
      nitrogen. These data may explain the selective pressures that support the
      coexistence of multiple isoforms of NadE in some prokaryotes.

PMID- 29581234
TI  - TRAF-interacting protein with forkhead-associated domain (TIFA) transduces DNA
      damage-induced activation of NF-kappaB.
AB  - DNA damage-induced NF-kappaB activation and the secretion of inflammatory
      cytokines play crucial roles in carcinogenesis and cellular senescence. However,
      the underlying mechanisms, especially the initial sensors and transducers
      connecting the nuclear DNA damage signal with cytoplasmic NF-kappaB activation
      remain incompletely understood. Here, we report that TRAF-interacting protein
      with forkhead-associated domain (TIFA), an established NF-kappaB activator in the
      cytosol, unexpectedly exhibited nuclear translocation and accumulation on damaged
      chromatin following genotoxic stress. Accordingly, we also found that DNA damage
      induced transcriptional activation and the resulting secretion of classic NF
      kappaB targets, including interleukin (IL)-6 and IL-8, was greatly enhanced in
      TIFA-overexpressing cells compared with control cells. Mechanistically, DNA
      damage-induced TIFA phosphorylation at threonine 9 (pThr-9), and this
      phosphorylation event, involving the pThr-binding forkhead-associated domain, was
      crucial for its enrichment on damaged chromatin and subsequent NF-kappaB
      activation. Moreover, in conjunction with its partner protein, the E3 ligase TNF
      receptor-associated factor 2 (TRAF2), TIFA relayed the DNA damage signals by
      stimulating ubiquitination of NF-kappaB essential modulator (NEMO), whose
      sumoylation, phosphorylation, and ubiquitination were critical for NF-kappaB's
      response to DNA damage. Consistently, TRAF2 knockdown suppressed TIFA
      overexpression-enhanced NEMO ubiquitination under genotoxic stress, and a
      unphosphorylatable Thr-9-mutated TIFA variant had only minor effects on NEMO poly
      ubiquitination. Finally, in agreement with the model of DNA damage-associated
      secretory senescence barrier against carcinogenesis, ectopic TIFA expression
      limited proliferation of multiple myeloma cancer cells. In conclusion our results
      indicate that TIFA functions as a key transducer in DNA damage-induced NF-kappaB
      activation.

PMID- 29581235
TI  - Myeloperoxidase-derived oxidants damage artery wall proteins in an animal model
      of chronic kidney disease-accelerated atherosclerosis.
AB  - Increased myeloperoxidase (MPO) levels and activity are associated with increased
      cardiovascular risk among individuals with chronic kidney disease (CKD). However,
      a lack of good animal models for examining the presence and catalytic activity of
      MPO in vascular lesions has impeded mechanistic studies into CKD-associated
      cardiovascular diseases. Here, we show for the first time that exaggerated
      atherosclerosis in a pathophysiologically relevant CKD mouse model is associated
      with increased macrophage-derived MPO activity. Male 7-week-old LDL receptor
      deficient mice underwent sham (control mice) or 5/6 nephrectomy and were fed
      either a low-fat or high-fat, high-cholesterol diet for 24 weeks, and the extents
      of atherosclerosis and vascular reactivity were assessed. MPO expression and
      oxidation products-protein-bound oxidized tyrosine moieties 3-chlorotyrosine, 3
      nitrotyrosine, and o,o'-dityrosine-were examined with immunoassays and confirmed
      with mass spectrometry (MS). As anticipated, the CKD mice had significantly
      higher plasma creatinine, urea nitrogen, and intact parathyroid hormone along
      with lower hematocrit and body weight. On both the diet regimens, CKD mice did
      not have hypertension but had lower cholesterol and triglyceride levels than the
      control mice. Despite the lower cholesterol levels, CKD mice had increased aortic
      plaque areas, fibrosis, and luminal narrowing. They also exhibited increased MPO
      expression and activity (i.e. increased oxidized tyrosines) that co-localized
      with infiltrating lesional macrophages and diminished vascular reactivity. In
      summary, unlike non-CKD mouse models of atherosclerosis, CKD mice exhibit
      increased MPO expression and catalytic activity in atherosclerotic lesions, which
      co-localize with lesional macrophages. These results implicate macrophage-derived
      MPO in CKD-accelerated atherosclerosis.

PMID- 29581236
TI  - Cryo-EM structure of Escherichia coli sigma70 RNA polymerase and promoter DNA
      complex revealed a role of sigma non-conserved region during the open complex
      formation.
AB  - First step of gene expression is transcribing the genetic information stored in
      DNA to RNA by the transcription machinery including RNA polymerase (RNAP). In
      Escherichia coli, a primary sigma70 factor forms the RNAP holoenzyme to express
      housekeeping genes. The sigma70 contains a large insertion between the conserved
      regions 1.2 and 2.1, the sigma non-conserved region (sigmaNCR), but its function
      remains to be elucidated. In this study, we determined the cryo-EM structures of
      the E. coli RNAP sigma70 holoenzyme and its complex with promoter DNA (open
      complex, RPo) at 4.2 and 5.75 A resolutions, respectively, to reveal native
      conformations of RNAP and DNA. The RPo structure presented here found an
      interaction between the sigmaNCR and promoter DNA just upstream of the -10
      element, which was not observed in a previously determined E. coli RNAP
      transcription initiation complex (RPo plus short RNA) structure by X-ray
      crystallography because of restraint of crystal packing effects. Disruption of
      the sigmaNCR and DNA interaction by the amino acid substitutions (R157A/R157E)
      influences the DNA opening around the transcription start site and therefore
      decreases the transcription activity of RNAP. We propose that the sigmaNCR and
      DNA interaction is conserved in proteobacteria, and RNAP in other bacteria
      replaces its role with a transcription factor.

PMID- 29581237
TI  - Female fertility preservation: past, present and future.
AB  - Anti-cancer therapy, particularly chemotherapy, damages ovarian follicles and
      promotes ovarian failure. The only pharmacological means for protecting the
      ovaries from chemotherapy-induced injury is gonadotrophin-releasing hormone
      agonist, but its efficiency remains controversial; ovarian transposition is used
      to shield the ovary from radiation when indicated. Until the late 1990s, the only
      option for fertility preservation and restoration in women with cancer was embryo
      cryopreservation. The development of other assisted reproductive technologies
      such as mature oocyte cryopreservation and in vitro maturation of oocytes has
      contributed to fertility preservation. Treatment regimens to obtain mature
      oocytes/embryos have been modified to overcome various limitations of
      conventional ovarian stimulation protocols. In the last decades, several centres
      have begun cryopreserving ovarian samples containing primordial follicles from
      young patients before anti-cancer therapy. The first live birth following
      implantation of cryopreserved-thawed ovarian tissue was reported in 2004; since
      then, the number has risen to more than 130. Nowadays, ovarian tissue
      cryopreservation can be combined with in vitro maturation and vitrification of
      oocytes. The use of cryopreserved oocytes eliminates the risk posed by ovarian
      implantation of reseeding the cancer. Novel methods for enhancing follicular
      survival after implantation are presently being studied. In addition, researchers
      are currently investigating agents for ovarian protection. It is expected that
      the risk of reimplantation of malignant cells with ovarian grafts will be
      overcome with the putative development of an artificial ovary and an efficient
      follicle class- and species-dependent in vitro system for culturing primordial
      follicles.

PMID- 29581238
TI  - Role of dysfunctional adipocytes in cholesterol-induced nonobese metabolic
      syndrome.
AB  - Many studies have reported the causes of obese metabolic syndrome (MS); however,
      the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated
      that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol
      induced NMS. Control (C), high cholesterol (HC) and HC with 10% fructose in
      drinking water (HCF) diets were fed to Sprague-Dawley rats for 12 weeks. After 12
      weeks, the body weights of the C- and HC-fed rats were comparable, but the
      weights of the HCF-fed rats were relatively low. Cholesterol caused metabolic
      problems such as high blood pressure, hypercholesterolemia and hypoinsulinemia.
      The HCF-fed rats exhibited whole-body insulin resistance with low circulating
      high-density lipoprotein levels. Increases in the tumor necrosis factor alpha
      level in the plasma, the number of CD68+ macrophages and the free nuclear factor
      kappaB level in gonadal white adipose tissue (gWAT) resulted in local
      inflammation, which appeared as inflamed dysfunctional gWAT. Reduced superoxide
      dismutases (SODs) deteriorate natural antioxidant defense systems and induce
      reactive oxygen species in gWAT. Dysregulation of plasma levels of catecholamine,
      adipokines (leptin and adiponectin), hormone-sensitive lipase and perilipin in
      cholesterol-induced inflamed adipose tissue contributed to increased lipolysis
      and increased circulating nonesterified fatty acids. Cholesterol activated
      inflammation, lipolysis and cell death in 3T3-L1 adipocytes. Moreover, Chol-3T3
      CM reduced the population of M2-type Raw264.7 macrophages, indicating that the
      macrophage polarization is mediated by cholesterol. Together, our findings
      indicate that inflamed dysfunctional adipocytes are critical in NMS, supporting
      the development of anti-inflammatory agents as potential therapeutic drugs for
      treating NMS.

PMID- 29581240
TI  - Intracranial Arterial Dolichoectasia and Stenosis: Risk Factors and Relation to
      Cerebral Small Vessel Disease.
AB  - BACKGROUND AND PURPOSE: Intracranial arterial dolichoectasia (IADE) is a poorly
      understood arteriopathy compared with intracranial atherosclerotic stenosis
      (ICAS). We aimed to investigate the risk factors of IADE and ICAS and their
      relationship with neuroimaging markers of cerebral small vessel disease in a
      population-based study. METHODS: This study comprised 1237 participants (aged
      57.2+/-9.4 years, 37.6% men) who underwent brain magnetic resonance imaging and
      magnetic resonance angiography. IADE was assessed based on basilar artery
      dolichoectasia (diameter, height of bifurcation, and laterality of basilar
      artery) and dilation of basilar artery and internal carotid artery (intracranial
      volume-adjusted diameter >=2 SD). ICAS was defined as any degree of stenosis in
      at least 1 intracranial artery. The neuroimaging markers of cerebral small vessel
      disease, including lacunes, white matter hyperintensities, microbleeds, dilated
      perivascular spaces, and brain atrophy, were evaluated. RESULTS: Basilar arterial
      dolichoectasia was observed in 3.6% (45/1237); intracranial arterial dilation in
      5.9% (67/1142); and ICAS in 15.7% (194/1237). Older age, higher systolic blood
      pressure, diabetes mellitus, higher LDL-C (low-density lipoprotein cholesterol)
      and lower HDL-C (high-density lipoprotein cholesterol) were associated with the
      presence of ICAS (all P<0.001), whereas only older age was associated with IADE.
      ICAS was associated with lacunes (odds ratio, 2.91; 95% confidence interval, 1.96
      4.34; P<0.001), increased white matter hyperintensities volume (beta+/-SE, 0.54+/
      0.13; P<0.001), and brain atrophy (beta+/-SE, -1.16+/-0.21; P<0.001), whereas
      basilar arterial dolichoectasia was mainly associated with dilated perivascular
      spaces in basal ganglia (odds ratio, 2.20; 95% confidence interval, 1.20-4.02;
      P=0.01) and, to a lesser extent, associated with lacunes and microbleeds.
      CONCLUSIONS: IADE and ICAS had different risk factor profiles and associated with
      different imaging phenotypes of cerebral small vessel disease, suggesting
      different underlying mechanisms.

PMID- 29581242
TI  - A Conversation with Iain Cheeseman.

PMID- 29581243
TI  - A Conversation with Monica Colaiacovo.

PMID- 29581241
TI  - Circulating microbiome in blood of different circulatory compartments.

PMID- 29581239
TI  - Role of IGF1 and EFN-EPH signaling in skeletal metabolism.
AB  - Insulin-like growth factor 1(IGF1) and ephrin ligand (EFN)-receptor (EPH)
      signaling are both crucial for bone cell function and skeletal development and
      maintenance. IGF1 signaling is the major mediator of growth hormone-induced bone
      growth, but a host of different signals and factors regulate IGF1 signaling at
      the systemic and local levels. Disruption of the Igf1 gene results in reduced
      peak bone mass in both experimental animal models and humans. Additionally, EFN
      EPH signaling is a complex system which, particularly through cell-cell
      interactions, contributes to the development and differentiation of many bone
      cell types. Recent evidence has demonstrated several ways in which the IGF1 and
      EFN-EPH signaling pathways interact with and depend upon each other to regulate
      bone cell function. While much remains to be elucidated, the interaction between
      these two signaling pathways opens a vast array of new opportunities for
      investigation into the mechanisms of and potential therapies for skeletal
      conditions such as osteoporosis and fracture repair.

PMID- 29581244
TI  - A Conversation with Kerry Bloom.

PMID- 29581245
TI  - Colorectal polyp risk is linked to an elevated level of homocysteine.
AB  - Several studies have reported an association between levels of folate,
      homocysteine, and vitamin B12 and the risk of colorectal polyps. Here, our aim is
      to examine the possible effect of folate, homocysteine, and vitamin B12 levels on
      the risk of colorectal polyps by means of meta-analysis based quantitative
      synthesis. According to our inclusion/exclusion criteria, a total of 13 case
      control studies were enrolled. The P-value of the association test, standard mean
      difference (SMD), and 95% confidence interval (CI) were calculated. Pooled
      analysis data showed a negative correlation between the risk of colorectal polyps
      and the levels of serum folate, red blood cell (RBC) folate, or vitamin B12 (all
      P>0.05). Nevertheless, for homocysteine level, we also observed a statistically
      significant difference between cases and controls in the overall and subgroup
      analysis of hospital-based control (HB), population-based control (PB), Chinese,
      Caucasian, or Asian (all P<0.05, SMD > 0). We found that increased levels of
      homocysteine may be statistically and significantly related to the risk of
      colorectal polyps.

PMID- 29581247
TI  - Association of single nucleotide polymorphisms in CACNA 1A/CACNA 1C/CACNA 1H
      calcium channel genes with diabetic peripheral neuropathy in Chinese population.
AB  - The present study was conducted to explore the correlations between single
      nucleotide polymorphisms (SNPs) in the calcium channel CACNA 1A, CACNA 1C, and
      CACNA 1H genes and diabetic peripheral neuropathy (DPN) amongst the Chinese
      population. In total, 281 patients diagnosed with type 2 diabetes participated in
      the present study. These patients were divided into the case group, which was
      subdivided into the DPN (143 cases) and the non-DPN groups (138 cases).
      Subsequently, 180 healthy individuals that had undergone routine health
      examinations were also recruited and assigned to the control group. PCR
      restriction fragment length polymorphism (PCR-RFLP) was used to detect the
      genotype and allele frequencies of CACNA 1A, CACNA 1C, and CACNA 1H genes;
      logistic regression analysis to investigate the association of gene polymorphisms
      with DNP. Gene-gene interactions were then detected by generalized multifactor
      dimensionality reduction (GMDR). The results revealed that CACNA 1A rs2248069 and
      rsl6030, CACNA 1C rs216008 and rs2239050, and CACNA 1H rs3794619, and rs7191246
      SNPs were all associated with DPN, while rs2248069, rsl6030, rs2239050, and
      rs7191246 polymorphisms were attributed to the susceptibility to DPN. It was also
      observed that the optimal models were three-, four- and five-dimensional models
      with a prediction accuracy of 61.05% and the greatest consistency of cross
      validation was 10/10. In summary, these findings demonstrated that the SNPs in
      the CACNA 1A, CACNA 1C, and CACNA 1H genes were involved in the pathophysiology
      of DPN. In addition, polymorphisms in the CACNA 1A, CACNA 1C, and CACNA 1H genes
      and their interactions also had effects on DPN.

PMID- 29581246
TI  - The association of neutrophil to lymphocyte ratio, mean platelet volume, and
      platelet distribution width with diabetic retinopathy and nephropathy: a meta
      analysis.
AB  - The aim of the present study was to investigate the correlation of neutrophil to
      lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet distribution
      width (PDW) with diabetic nephropathy (DN) and diabetic retinopathy (DR). We
      searched for eligible studies from PubMed, Embase, Web of Science, and CNKI up to
      1 December 2017. Standardized mean difference (SMD) was calculated with a
      confidence interval (CI) of 95%. A total of 48 studies were included in our meta
      analysis. Compared with patients with type II diabetes mellitus (T2DM) and
      without DR, NLR, MPV, and PDW were higher in patients with DR (SMD = 0.77; 95%
      CI: 0.49-1.05; P<0.001; SMD = 0.68; 95% CI: 0.36-0.99; P<0.001; SMD = 0.52; 95%
      CI: 0.28-0.76; P<0.01). Compared with patients with T2DM and without DN, NLR,
      MPV, and PDW were higher in patients with DN (SMD = 0.63; 95% CI: 0.43-0.83;
      P<0.001; SMD = 0.81; 95% CI: 0.36-1.25; P<0.001; SMD = 0.70; 95% CI: 0.50-0.90;
      P<0.001). We also found that MPV was strongly associated with the severity of DR,
      and NLR was closely related to the degree of DN. Our findings indicated that NLR,
      MPV, and PDW could be recommended as inexpensive diagnostic biomarkers for DN and
      DR. However, considering several limitations in the present study, further high
      quality clinical studies should be performed to investigate the relationship of
      NLR, MPV, and PDW to DN and DR.

PMID- 29581248
TI  - Discussion comment on melting criteria and imaging spectroradiometry in laser
      heated diamond-cell experiments (by R. Jeanloz & A. Kavner).
AB  - Jeanloz & Kavner have a very timely contribution which raises some very important
      issues concerning the measurement of temperature using spectroradiometry. In this
      discussion of the paper, we intend to show that while all the issues raised by
      the authors should be of real concern to all workers, some of the issues have
      indeed been resolved with improved technique. However, we agree with the authorn
      that there are several issues that must be resolved and caution is necessary in
      interpreting the observations.

PMID- 29581249
TI  - Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592)
      protects against cisplatin-induced acute kidney injury.
AB  - Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies.
      Activation of hypoxia-inducible transcription factor (HIF) has been identified as
      an important mechanism of cellular adaptation to low oxygen. Preconditional HIF
      activation protects against AKI, suggesting a new approach in AKI treatment. HIF
      is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation
      of specific prolyl residues of the regulative alpha-subunits by HIF prolyl
      hydroxylases (PHD). FG-4592 is a novel, orally active, small-molecule HIF PHD
      inhibitor for the treatment of anemia in patients with chronic kidney disease
      (CKD). The current study aimed to evaluate the effect of FG-4592 (Roxadustat) on
      cis-diamminedichloroplatinum (cisplatin)-induced kidney injury. In mice,
      pretreatment with FG-4592 markedly ameliorated cisplatin-induced kidney injury as
      shown by the improved renal function (blood urea nitrogen (BUN), serum creatinine
      (Scr), and cystatin C) and kidney morphology (periodic acid-Schiff (PAS)
      staining) in line with a robust blockade of renal tubular injury markers of
      kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin
      (NGAL). Meanwhile, the renal apoptosis and inflammation induced by cisplatin were
      also strikingly attenuated in FG-4592-treated mice. Along with the protective
      effects shown above, FG-4592 pretreatment strongly enhanced HIF-1alpha in tubular
      cells, as well as the expressions of HIF target genes. FG-4592 alone did not
      affect the renal function and morphology in mice. In vitro, FG-4592 treatment
      significantly up-regulated HIF-1alpha and protected the tubular cells against
      cisplatin-induced apoptosis. In summary, FG-4592 treatment remarkably ameliorated
      the cisplatin-induced kidney injury possibly through the stabilization of HIF.
      Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also
      could be extended to AKI.

PMID- 29581251
TI  - The opportunity cost of animal based diets exceeds all food losses.
AB  - Food loss is widely recognized as undermining food security and environmental
      sustainability. However, consumption of resource-intensive food items instead of
      more efficient, equally nutritious alternatives can also be considered as an
      effective food loss. Here we define and quantify these opportunity food losses as
      the food loss associated with consuming resource-intensive animal-based items
      instead of plant-based alternatives which are nutritionally comparable, e.g., in
      terms of protein content. We consider replacements that minimize cropland use for
      each of the main US animal-based food categories. We find that although the
      characteristic conventional retail-to-consumer food losses are ~30% for plant and
      animal products, the opportunity food losses of beef, pork, dairy, poultry, and
      eggs are 96%, 90%, 75%, 50%, and 40%, respectively. This arises because plant
      based replacement diets can produce 20-fold and twofold more nutritionally
      similar food per cropland than beef and eggs, the most and least resource
      intensive animal categories, respectively. Although conventional and opportunity
      food losses are both targets for improvement, the high opportunity food losses
      highlight the large potential savings beyond conventionally defined food losses.
      Concurrently replacing all animal-based items in the US diet with plant-based
      alternatives will add enough food to feed, in full, 350 million additional
      people, well above the expected benefits of eliminating all supply chain food
      waste. These results highlight the importance of dietary shifts to improving food
      availability and security.

PMID- 29581250
TI  - LSD1 activates a lethal prostate cancer gene network independently of its
      demethylase function.
AB  - Medical castration that interferes with androgen receptor (AR) function is the
      principal treatment for advanced prostate cancer. However, clinical progression
      is universal, and tumors with AR-independent resistance mechanisms appear to be
      increasing in frequency. Consequently, there is an urgent need to develop new
      treatments targeting molecular pathways enriched in lethal prostate cancer.
      Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important
      regulator of gene expression. Here, we show that LSD1 promotes the survival of
      prostate cancer cells, including those that are castration-resistant,
      independently of its demethylase function and of the AR. Importantly, this effect
      is explained in part by activation of a lethal prostate cancer gene network in
      collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule
      LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and
      suppresses castration-resistant prostate cancer cell viability demonstrates the
      potential of LSD1 inhibition in this disease.

PMID- 29581252
TI  - Global increase and geographic convergence in antibiotic consumption between 2000
      and 2015.
AB  - Tracking antibiotic consumption patterns over time and across countries could
      inform policies to optimize antibiotic prescribing and minimize antibiotic
      resistance, such as setting and enforcing per capita consumption targets or
      aiding investments in alternatives to antibiotics. In this study, we analyzed the
      trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries
      and projected total global antibiotic consumption through 2030. Between 2000 and
      2015, antibiotic consumption, expressed in defined daily doses (DDD), increased
      65% (21.1-34.8 billion DDDs), and the antibiotic consumption rate increased 39%
      (11.3-15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low-
      and middle-income countries (LMICs), where rising consumption was correlated with
      gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income
      countries (HICs), although overall consumption increased modestly, DDDs per 1,000
      inhabitants per day fell 4%, and there was no correlation with GDPPC. Of
      particular concern was the rapid increase in the use of last-resort compounds,
      both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and
      polymyxins. Projections of global antibiotic consumption in 2030, assuming no
      policy changes, were up to 200% higher than the 42 billion DDDs estimated in
      2015. Although antibiotic consumption rates in most LMICs remain lower than in
      HICs despite higher bacterial disease burden, consumption in LMICs is rapidly
      converging to rates similar to HICs. Reducing global consumption is critical for
      reducing the threat of antibiotic resistance, but reduction efforts must balance
      access limitations in LMICs and take account of local and global resistance
      patterns.

PMID- 29581253
TI  - NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly
      and cell motility.
AB  - Actin, one of the most abundant proteins in nature, participates in countless
      cellular functions ranging from organelle trafficking and pathogen motility to
      cell migration and regulation of gene transcription. Actin's cellular activities
      depend on the dynamic transition between its monomeric and filamentous forms, a
      process exquisitely regulated in cells by a large number of actin-binding and
      signaling proteins. Additionally, several posttranslational modifications control
      the cellular functions of actin, including most notably N-terminal (Nt)
      acetylation, a prevalent modification throughout the animal kingdom. However, the
      biological role and mechanism of actin Nt-acetylation are poorly understood, and
      the identity of actin's N-terminal acetyltransferase (NAT) has remained a
      mystery. Here, we reveal that NAA80, a suggested NAT enzyme whose substrate
      specificity had not been characterized, is Nt-acetylating actin. We further show
      that actin Nt-acetylation plays crucial roles in cytoskeletal assembly in vitro
      and in cells. The absence of Nt-acetylation leads to significant differences in
      the rates of actin filament depolymerization and elongation, including elongation
      driven by formins, whereas filament nucleation by the Arp2/3 complex is mostly
      unaffected. NAA80-knockout cells display severely altered cytoskeletal
      organization, including an increase in the ratio of filamentous to globular
      actin, increased filopodia and lamellipodia formation, and accelerated cell
      motility. Together, the results demonstrate NAA80's role as actin's NAT and
      reveal a crucial role for actin Nt-acetylation in the control of cytoskeleton
      structure and dynamics.

PMID- 29581254
TI  - A zipped-helix cap potentiates HAMP domain control of chemoreceptor signaling.
AB  - Environmental awareness is an essential attribute for all organisms. The
      chemotaxis system of Escherichia coli provides a powerful experimental model for
      the investigation of stimulus detection and signaling mechanisms at the molecular
      level. These bacteria sense chemical gradients with transmembrane proteins
      [methyl-accepting chemotaxis proteins (MCPs)] that have an extracellular ligand
      binding domain and intracellular histidine kinases, adenylate cyclases, methyl
      accepting proteins, and phosphatases (HAMP) and signaling domains that govern
      locomotor behavior. HAMP domains are versatile input-output elements that operate
      in a variety of bacterial signaling proteins, including the sensor kinases of two
      component regulatory systems. The MCP HAMP domain receives stimulus information
      and in turn modulates output signaling activity. This study describes mutants of
      the Escherichia coli serine chemoreceptor, Tsr, that identify a heptad-repeat
      structural motif (LLF) at the membrane-proximal end of the receptor signaling
      domain that is critical for HAMP output control. The homodimeric Tsr signaling
      domain is an extended, antiparallel, four-helix bundle that controls the activity
      of an associated kinase. The N terminus of each subunit adjoins the HAMP domain;
      the LLF residues lie at the C terminus of the methylation-helix bundle. We found,
      by using in vivo Forster resonance energy transfer kinase assays, that most amino
      acid replacements at any of the LLF residues abrogate chemotactic responses to
      serine and lock Tsr output in a kinase-active state, impervious to HAMP-mediated
      down-regulation. We present evidence that the LLF residues may function like a
      leucine zipper to promote stable association of the C-terminal signaling helices,
      thereby creating a metastable helix-packing platform for the N-terminal signaling
      helices that facilitates conformational control by the HAMP domains in MCP-family
      chemoreceptors.

PMID- 29581255
TI  - Anti-CTLA-4 therapy requires an Fc domain for efficacy.
AB  - Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen
      (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In
      mouse tumor models, the response to antibodies against CTLA-4 depends entirely on
      expression of the Fcgamma receptor (FcgammaR), which may facilitate antibody
      dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade
      remains unknown. To understand the role of CTLA-4 blockade in the complete
      absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy
      chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc
      portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4
      and its ligand by occluding the ligand-binding motif on CTLA-4 as shown
      crystallographically. We used H11 to visualize CTLA-4 expression in vivo using
      whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely
      confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4
      blockade has minimal effects on antitumor responses. Installation of the murine
      IgG2a constant region on H11 dramatically enhances its antitumor response.
      Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized
      therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding
      antibodies require an Fc domain for antitumor effect.

PMID- 29581257
TI  - Reversal of orbital angular momentum arising from an extreme Doppler shift.
AB  - The linear Doppler shift is familiar as the rise and fall in pitch of a siren as
      it passes by. Less well known is the rotational Doppler shift, proportional to
      the rotation rate between source and receiver, multiplied by the angular momentum
      carried by the beam. In extreme cases the Doppler shift can be larger than the
      rest-frame frequency and for a red shift, the observed frequency then becomes
      "negative." In the linear case, this effect is associated with the time reversal
      of the received signal, but it can be observed only with supersonic relative
      motion between the source and receiver. However, the rotational case is
      different; if the radius of rotation is smaller than the wavelength, then the
      velocities required to observe negative frequencies are subsonic. Using an
      acoustic source at [Formula: see text]100 Hz we create a rotational Doppler shift
      larger than the laboratory-frame frequency. We observe that once the red-shifted
      wave passes into the "negative frequency" regime, the angular momentum associated
      with the sound is reversed in sign compared with that of the laboratory frame.
      These low-velocity laboratory realizations of extreme Doppler shifts have
      relevance to superoscillatory fields and offer unique opportunities to probe
      interactions with rotating bodies and aspects of pseudorelativistic frame
      translation.

PMID- 29581256
TI  - PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors.
AB  - Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3
      mediated activation of MLKL. However, the signaling process leading to
      necroptotic death remains to be elucidated. In this study, we found that PUMA, a
      proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an
      RIP3/MLKL-dependent manner following induction of necroptosis. The induction of
      PUMA, which is mediated by autocrine TNF-alpha and enhanced NF-kappaB activity,
      contributes to necroptotic death in RIP3-expressing cells with caspases
      inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA
      and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3
      and MLKL phosphorylation in a positive feedback loop. Furthermore, deletion of
      PUMA partially rescues necroptosis-mediated developmental defects in FADD
      deficient embryos. Collectively, our results reveal a signal amplification
      mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF
      driven necroptotic death in vitro and in vivo.

PMID- 29581258
TI  - CSI1, PATROL1, and exocyst complex cooperate in delivery of cellulose synthase
      complexes to the plasma membrane.
AB  - Cellulose synthesis occurs exclusively at the plasma membrane by cellulose
      synthase complexes (CSCs). Therefore, delivery of CSCs to discrete sites at the
      plasma membrane is critical for cellulose synthesis. Despite their significance,
      the delivery of CSCs is poorly understood. Here we used proteomics approaches,
      functional genetics, and live cell imaging to show that the de novo secretion of
      CSCs is mediated by cooperation among cellulose synthase interactive 1 (CSI1),
      the plant-specific protein PATROL1, and exocyst complex in Arabidopsis thaliana
      We propose that CSI1 plays a role in marking the docking site, which allows CSCs
      containing vesicles access to the plasma membrane through its interaction with
      microtubules. PATROL1 assists in exocytosis by its interaction with multiple
      components, including CSI1, CSCs, and exocyst subunits. Both PATROL1 and the
      exocyst complex determine the rate of delivery of CSCs to the plasma membrane. By
      monitoring the exocyst complex, PATROL1, CSI1, and CSCs dynamics in real time, we
      present a timeline of events for exocytosis of CSCs. Our findings provide unique
      insights into the evolution of exocytosis in eukaryotes.

PMID- 29581259
TI  - LTP requires postsynaptic PDZ-domain interactions with glutamate
      receptor/auxiliary protein complexes.
AB  - Long-term potentiation (LTP) is a persistent strengthening of synaptic
      transmission in the brain and is arguably the most compelling cellular and
      molecular model for learning and memory. Previous work found that both AMPA
      receptors and exogenously expressed kainate receptors are equally capable of
      expressing LTP, despite their limited homology and their association with
      distinct auxiliary subunits, indicating that LTP is far more promiscuous than
      previously thought. What might these two subtypes of glutamate receptor have in
      common? Using a single-cell molecular replacement strategy, we demonstrate that
      the AMPA receptor auxiliary subunit TARP gamma-8, via its PDZ-binding motif, is
      indispensable for both basal synaptic transmission and LTP. Remarkably, kainate
      receptors and their auxiliary subunits Neto proteins share the same requirement
      of PDZ-binding domains for synaptic trafficking and LTP. Together, these results
      suggest that a minimal postsynaptic requirement for LTP is the PDZ binding of
      glutamate receptors/auxiliary subunits to PSD scaffolding proteins.

PMID- 29581260
TI  - Molecular and structural architecture of polyQ aggregates in yeast.
AB  - Huntington's disease is caused by the expansion of a polyglutamine (polyQ) tract
      in the N-terminal exon of huntingtin (HttEx1), but the cellular mechanisms
      leading to neurodegeneration remain poorly understood. Here we present in situ
      structural studies by cryo-electron tomography of an established yeast model
      system of polyQ toxicity. We find that expression of polyQ-expanded HttEx1
      results in the formation of unstructured inclusion bodies and in some cases
      fibrillar aggregates. This contrasts with recent findings in mammalian cells,
      where polyQ inclusions were exclusively fibrillar. In yeast, polyQ toxicity
      correlates with alterations in mitochondrial and lipid droplet morphology, which
      do not arise from physical interactions with inclusions or fibrils. Quantitative
      proteomic analysis shows that polyQ aggregates sequester numerous cellular
      proteins and cause a major change in proteome composition, most significantly in
      proteins related to energy metabolism. Thus, our data point to a multifaceted
      toxic gain-of-function of polyQ aggregates, driven by sequestration of endogenous
      proteins and mitochondrial and lipid droplet dysfunction.

PMID- 29581261
TI  - Mechanistic insights into staphylopine-mediated metal acquisition.
AB  - Metal acquisition is vital to pathogens for successful infection within hosts.
      Staphylopine (StP), a broad-spectrum metallophore biosynthesized by the major
      human pathogen, Staphylococcus aureus, plays a central role in transition-metal
      acquisition and bacterial virulence. The StP-like biosynthesis loci are present
      in various pathogens, and the proteins responsible for StP/metal transportation
      have been determined. However, the molecular mechanisms of how StP/metal
      complexes are recognized and transported remain unknown. We report multiple
      structures of the extracytoplasmic solute-binding protein CntA from the StP/metal
      transportation system in apo form and in complex with StP and three different
      metals. We elucidated a sophisticated metal-bound StP recognition mechanism and
      determined that StP/metal binding triggers a notable interdomain conformational
      change in CntA. Furthermore, CRISPR/Cas9-mediated single-base substitution
      mutations and biochemical analysis highlight the importance of StP/metal
      recognition for StP/metal acquisition. These discoveries provide critical
      insights into the study of novel metal-acquisition mechanisms in microbes.

PMID- 29581262
TI  - Continuous plating/stripping behavior of solid-state lithium metal anode in a 3D
      ion-conductive framework.
AB  - The increasing demands for efficient and clean energy-storage systems have
      spurred the development of Li metal batteries, which possess attractively high
      energy densities. For practical application of Li metal batteries, it is vital to
      resolve the intrinsic problems of Li metal anodes, i.e., the formation of Li
      dendrites, interfacial instability, and huge volume changes during cycling.
      Utilization of solid-state electrolytes for Li metal anodes is a promising
      approach to address those issues. In this study, we use a 3D garnet-type ion
      conductive framework as a host for the Li metal anode and study the plating and
      stripping behaviors of the Li metal anode within the solid ion-conductive host.
      We show that with a solid-state ion-conductive framework and a planar current
      collector at the bottom, Li is plated from the bottom and rises during
      deposition, away from the separator layer and free from electrolyte penetration
      and short circuit. Owing to the solid-state deposition property, Li grows
      smoothly in the pores of the garnet host without forming Li dendrites. The
      dendrite-free deposition and continuous rise/fall of Li metal during
      plating/stripping in the 3D ion-conductive host promise a safe and durable Li
      metal anode. The solid-state Li anode shows stable cycling at 0.5 mA cm-2 for 300
      h with a small overpotential, showing a significant improvement compared with
      reported Li anodes with ceramic electrolytes. By fundamentally eliminating the
      dendrite issue, the solid Li metal anode shows a great potential to build safe
      and reliable Li metal batteries.

PMID- 29581264
TI  - Correction for Bernardo-Seisdedos et al., Structural basis and energy landscape
      for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel.

PMID- 29581263
TI  - Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin
      oxidoreductase from Moorella thermoacetica.
AB  - Pyruvate:ferredoxin oxidoreductase (PFOR) is a microbial enzyme that uses
      thiamine pyrophosphate (TPP), three [4Fe-4S] clusters, and coenzyme A (CoA) in
      the reversible oxidation of pyruvate to generate acetyl-CoA and carbon dioxide.
      The two electrons that are generated as a result of pyruvate decarboxylation are
      used in the reduction of low potential ferredoxins, which provide reducing
      equivalents for central metabolism, including the Wood-Ljungdahl pathway. PFOR is
      a member of the 2-oxoacid:ferredoxin oxidoreductase (OFOR) superfamily, which
      plays major roles in both microbial redox reactions and carbon dioxide fixation.
      Here, we present a set of crystallographic snapshots of the best-studied member
      of this superfamily, the PFOR from Moorella thermoacetica (MtPFOR). These
      snapshots include the native structure, those of lactyl-TPP and acetyl-TPP
      reaction intermediates, and the first of an OFOR with CoA bound. These structural
      data reveal the binding site of CoA as domain III, the function of which in OFORs
      was previously unknown, and establish sequence motifs for CoA binding in the OFOR
      superfamily. MtPFOR structures further show that domain III undergoes a
      conformational change upon CoA binding that seals off the active site and
      positions the thiolate of CoA directly adjacent to the TPP cofactor. These
      structural findings provide a molecular basis for the experimental observation
      that CoA binding accelerates catalysis by 105-fold.

PMID- 29581265
TI  - Circadian clock activity of cryptochrome relies on tryptophan-mediated
      photoreduction.
AB  - Cryptochromes (CRYs) entrain the circadian clocks of plants and animals to light.
      Irradiation of the Drosophila cryptochrome (dCRY) causes reduction of an oxidized
      flavin cofactor by a chain of conserved tryptophan (Trp) residues. However, it is
      unclear how redox chemistry within the Trp chain couples to dCRY-mediated
      signaling. Here, we show that substitutions of four key Trp residues to redox
      active tyrosine and redox-inactive phenylalanine tune the light sensitivity of
      dCRY photoreduction, conformational activation, cellular stability, and targeted
      degradation of the clock protein timeless (TIM). An essential surface Trp gates
      electron flow into the flavin cofactor, but can be relocated for enhanced
      photoactivation. Differential effects of Trp-mediated flavin photoreduction on
      cellular turnover of TIM and dCRY indicate that these activities are separated in
      time and space. Overall, the dCRY Trp chain has evolutionary importance for light
      sensing, and its manipulation has implications for optogenetic applications of
      CRYs.

PMID- 29581266
TI  - Cracking the social code of speech prosody using reverse correlation.
AB  - Human listeners excel at forming high-level social representations about each
      other, even from the briefest of utterances. In particular, pitch is widely
      recognized as the auditory dimension that conveys most of the information about a
      speaker's traits, emotional states, and attitudes. While past research has
      primarily looked at the influence of mean pitch, almost nothing is known about
      how intonation patterns, i.e., finely tuned pitch trajectories around the mean,
      may determine social judgments in speech. Here, we introduce an experimental
      paradigm that combines state-of-the-art voice transformation algorithms with
      psychophysical reverse correlation and show that two of the most important
      dimensions of social judgments, a speaker's perceived dominance and
      trustworthiness, are driven by robust and distinguishing pitch trajectories in
      short utterances like the word "Hello," which remained remarkably stable whether
      male or female listeners judged male or female speakers. These findings reveal a
      unique communicative adaptation that enables listeners to infer social traits
      regardless of speakers' physical characteristics, such as sex and mean pitch. By
      characterizing how any given individual's mental representations may differ from
      this generic code, the method introduced here opens avenues to explore dysprosody
      and social-cognitive deficits in disorders like autism spectrum and
      schizophrenia. In addition, once derived experimentally, these prototypes can be
      applied to novel utterances, thus providing a principled way to modulate
      personality impressions in arbitrary speech signals.

PMID- 29581268
TI  - IRF9 and unphosphorylated STAT2 cooperate with NF-kappaB to drive IL6 expression.
AB  - In response to IFNbeta, the IL6 gene is activated, modestly at early times by
      ISGF3 (IRF9 plus tyrosine-phosphorylated STATs 1 and 2), and strongly at late
      times by U-ISGF3 (IRF9 plus U-STATs 1 and 2, lacking tyrosine phosphorylation). A
      classical IFN-stimulated response element (ISRE) at -1,513 to -1,526 in the human
      IL6 promoter is required. Pretreating cells with IFNbeta or increasing the
      expression of U-STAT2 and IRF9 exogenously greatly enhances IL6 expression in
      response to the classical NF-kappaB activators IL1, TNF, and LPS. U-STAT2 binds
      tightly to IRF9, the DNA binding subunit of ISGF3, and also to the p65 subunit of
      NF-kappaB. Therefore, as shown by ChIP analyses, U-STAT2 can bridge the ISRE and
      kappaB elements in the IL6 promoter. In some cancer cells, the protumorigenic
      activation of STAT3 will be enhanced by the increased synthesis of IL6 that is
      facilitated by high expression of U-STAT2 and IRF9.

PMID- 29581267
TI  - Exploring the structural origins of cryptic sites on proteins.
AB  - Molecular dynamics (MD) simulations of proteins reveal the existence of many
      transient surface pockets; however, the factors determining what small subset of
      these represent druggable or functionally relevant ligand binding sites, called
      "cryptic sites," are not understood. Here, we examine multiple X-ray structures
      for a set of proteins with validated cryptic sites, using the computational hot
      spot identification tool FTMap. The results show that cryptic sites in ligand
      free structures generally have a strong binding energy hot spot very close by. As
      expected, regions around cryptic sites exhibit above-average flexibility, and
      close to 50% of the proteins studied here have unbound structures that could
      accommodate the ligand without clashes. Nevertheless, the strong hot spot
      neighboring each cryptic site is almost always exploited by the bound ligand,
      suggesting that binding may frequently involve an induced fit component. We
      additionally evaluated the structural basis for cryptic site formation, by
      comparing unbound to bound structures. Cryptic sites are most frequently occluded
      in the unbound structure by intrusion of loops (22.5%), side chains (19.4%), or
      in some cases entire helices (5.4%), but motions that create sites that are too
      open can also eliminate pockets (19.4%). The flexibility of cryptic sites
      frequently leads to missing side chains or loops (12%) that are particularly
      evident in low resolution crystal structures. An interesting observation is that
      cryptic sites formed solely by the movement of side chains, or of backbone
      segments with fewer than five residues, result only in low affinity binding sites
      with limited use for drug discovery.

PMID- 29581269
TI  - Internal states and extrinsic factors both determine monkey vocal production.
AB  - A key question for understanding speech evolution is whether or not the
      vocalizations of our closest living relatives-nonhuman primates-represent the
      precursors to speech. Some believe that primate vocalizations are not volitional
      but are instead inextricably linked to internal states like arousal and thus bear
      little resemblance to human speech. Others disagree and believe that since many
      primates can use their vocalizations strategically, this demonstrates a degree of
      voluntary vocal control. In the current study, we present a behavioral paradigm
      that reliably elicits different types of affiliative vocalizations from marmoset
      monkeys while measuring their heart rate fluctuations using noninvasive
      electromyography. By modulating both the physical distance between marmosets and
      the sensory information available to them, we find that arousal levels are
      linked, but not inextricably, to vocal production. Different arousal levels are,
      generally, associated with changes in vocal acoustics and the drive to produce
      different call types. However, in contexts where marmosets are interacting, the
      production of these different call types is also affected by extrinsic factors
      such as the timing of a conspecific's vocalization. These findings suggest that
      variability in vocal output as a function of context might reflect trade-offs
      between the drive to perpetuate vocal contact and conserving energy.

PMID- 29581270
TI  - Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but
      impairs access to inactivated state after opening.
AB  - A de novo mutation in the KCND2 gene, which encodes the Kv4.2 K+ channel, was
      identified in twin boys with intractable, infant-onset epilepsy and autism. Kv4.2
      channels undergo closed-state inactivation (CSI), a mechanism by which channels
      inactivate without opening during subthreshold depolarizations. CSI dynamically
      modulates neuronal excitability and action potential back propagation in response
      to excitatory synaptic input, controlling Ca2+ influx into dendrites and
      regulating spike timing-dependent plasticity. Here, we show that the V404M
      mutation specifically affects the mechanism of CSI, enhancing the inactivation of
      channels that have not opened while dramatically impairing the inactivation of
      channels that have opened. The mutation gives rise to these opposing effects by
      increasing the stability of the inactivated state and in parallel, profoundly
      slowing the closure of open channels, which according to our data, is required
      for CSI. The larger volume of methionine compared with valine is a major factor
      underlying altered inactivation gating. Our results suggest that V404M increases
      the strength of the physical interaction between the pore gate and the voltage
      sensor regardless of whether the gate is open or closed. Furthermore, in contrast
      to previous proposals, our data strongly suggest that physical coupling between
      the voltage sensor and the pore gate is maintained in the inactivated state. The
      state-dependent effects of V404M on CSI are expected to disturb the regulation of
      neuronal excitability and the induction of spike timing-dependent plasticity. Our
      results strongly support a role for altered CSI gating in the etiology of
      epilepsy and autism in the affected twins.

PMID- 29581271
TI  - Levy flight movements prevent extinctions and maximize population abundances in
      fragile Lotka-Volterra systems.
AB  - Multiple-scale mobility is ubiquitous in nature and has become instrumental for
      understanding and modeling animal foraging behavior. However, the impact of
      individual movements on the long-term stability of populations remains largely
      unexplored. We analyze deterministic and stochastic Lotka-Volterra systems, where
      mobile predators consume scarce resources (prey) confined in patches. In fragile
      systems (that is, those unfavorable to species coexistence), the predator species
      has a maximized abundance and is resilient to degraded prey conditions when
      individual mobility is multiple scaled. Within the Levy flight model, highly
      superdiffusive foragers rarely encounter prey patches and go extinct, whereas
      normally diffusing foragers tend to proliferate within patches, causing
      extinctions by overexploitation. Levy flights of intermediate index allow a
      sustainable balance between patch exploitation and regeneration over wide ranges
      of demographic rates. Our analytical and simulated results can explain field
      observations and suggest that scale-free random movements are an important
      mechanism by which entire populations adapt to scarcity in fragmented ecosystems.

PMID- 29581273
TI  - Correction for Paluck et al., Changing climates of conflict: A social network
      experiment in 56 schools.

PMID- 29581272
TI  - Endothelial GqPCR activity controls capillary electrical signaling and brain
      blood flow through PIP2 depletion.
AB  - Brain capillaries play a critical role in sensing neural activity and translating
      it into dynamic changes in cerebral blood flow to serve the metabolic needs of
      the brain. The molecular cornerstone of this mechanism is the capillary
      endothelial cell inward rectifier K+ (Kir2.1) channel, which is activated by
      neuronal activity-dependent increases in external K+ concentration, producing a
      propagating hyperpolarizing electrical signal that dilates upstream arterioles.
      Here, we identify a key regulator of this process, demonstrating that
      phosphatidylinositol 4,5-bisphosphate (PIP2) is an intrinsic modulator of
      capillary Kir2.1-mediated signaling. We further show that PIP2 depletion through
      activation of Gq protein-coupled receptors (GqPCRs) cripples capillary-to
      arteriole signal transduction in vitro and in vivo, highlighting the potential
      regulatory linkage between GqPCR-dependent and electrical neurovascular-coupling
      mechanisms. These results collectively show that PIP2 sets the gain of capillary
      initiated electrical signaling by modulating Kir2.1 channels. Endothelial PIP2
      levels would therefore shape the extent of retrograde signaling and modulate
      cerebral blood flow.

PMID- 29581274
TI  - Loss of TDP43 inhibits progression of triple-negative breast cancer in
      coordination with SRSF3.
AB  - Aberrant alternative splicing has been highlighted as a potential hallmark of
      cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important
      splicing regulator responsible for the unique splicing profile in triple-negative
      breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in
      TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression,
      including proliferation and metastasis, and overexpression of TDP43 promotes
      proliferation and malignancy of mammary epithelial cells. Deep sequencing
      analysis and functional experiments indicate that TDP43 alters most splicing
      events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in
      the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific
      splicing events, including downstream genes PAR3 and NUMB The effect of reduced
      metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by
      the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3
      complex and downstream PAR3 isoform are potential therapeutic targets for TNBC.

PMID- 29581275
TI  - IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol ring
      cleaving hydrolase.
AB  - Mycobacterium tuberculosis (Mtb) grows on host-derived cholesterol during
      infection. IpdAB, found in all steroid-degrading bacteria and a determinant of
      pathogenicity, has been implicated in the hydrolysis of the last steroid ring.
      Phylogenetic analyses revealed that IpdAB orthologs form a clade of CoA
      transferases (CoTs). In a coupled assay with a thiolase, IpdAB transformed the
      cholesterol catabolite (R)-2-(2-carboxyethyl)-3-methyl-6-oxocyclohex-1-ene-1
      carboxyl-CoA (COCHEA-CoA) and CoASH to 4-methyl-5-oxo-octanedioyl-CoA (MOODA-CoA)
      and acetyl-CoA with high specificity (kcat/Km = 5.8 +/- 0.8 * 104 M-1?s-1). The
      structure of MOODA-CoA was consistent with IpdAB hydrolyzing COCHEA-CoA to a beta
      keto-thioester, a thiolase substrate. Contrary to characterized CoTs, IpdAB
      exhibited no activity toward small CoA thioesters. Further, IpdAB lacks the
      catalytic glutamate residue that is conserved in the beta-subunit of
      characterized CoTs and a glutamyl-CoA intermediate was not trapped during
      turnover. By contrast, Glu105A, conserved in the alpha-subunit of IpdAB, was
      essential for catalysis. A crystal structure of the IpdAB.COCHEA-CoA complex,
      solved to 1.4 A, revealed that Glu105A is positioned to act as a catalytic base.
      Upon titration with COCHEA-CoA, the E105AA variant accumulated a yellow-colored
      species (lambdamax = 310 nm; Kd = 0.4 +/- 0.2 MUM) typical of beta-keto enolates.
      In the presence of D2O, IpdAB catalyzed the deuteration of COCHEA-CoA adjacent to
      the hydroxylation site at rates consistent with kcat Based on these data and
      additional IpdAB variants, we propose a retro-Claisen condensation-like mechanism
      for the IpdAB-mediated hydrolysis of COCHEA-CoA. This study expands the range of
      known reactions catalyzed by the CoT superfamily and provides mechanistic insight
      into an important determinant of Mtb pathogenesis.

PMID- 29581276
TI  - Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces
      cerevisiae genome.
AB  - We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single
      nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine
      dimers and (6-4) pyrimidine-pyrimidone photoproducts in the Saccharomyces
      cerevisiae genome. We find that these photoproducts are removed from the genome
      primarily by incisions 13-18 nucleotides 5' and 6-7 nucleotides 3' to the UV
      damage that generate 21- to 27-nt-long excision products. Analyses of the
      excision repair kinetics both in single genes and at the genome-wide level reveal
      strong transcription-coupled repair of the transcribed strand at early time
      points followed by predominantly nontranscribed strand repair at later stages. We
      have also characterized the excision repair level as a function of the
      transcription level. The availability of high-resolution and dynamic repair maps
      should aid in future repair and mutagenesis studies in this model organism.

PMID- 29581278
TI  - Rapid enhancement of chemical weathering recorded by extremely light seawater
      lithium isotopes at the Permian-Triassic boundary.
AB  - Lithium (Li) isotope analyses of sedimentary rocks from the Meishan section in
      South China reveal extremely light seawater Li isotopic signatures at the Permian
      Triassic boundary (PTB), which coincide with the most severe mass extinction in
      the history of animal life. Using a dynamic seawater lithium box model, we show
      that the light seawater Li isotopic signatures can be best explained by a
      significant influx of riverine [Li] with light delta7Li to the ocean realm. The
      seawater Li isotope excursion started >=300 Ky before and persisted up to the
      main extinction event, which is consistent with the eruption time of the Siberian
      Traps. The eruption of the Siberian Traps exposed an enormous amount of fresh
      basalt and triggered CO2 release, rapid global warming, and acid rains, which in
      turn led to a rapid enhancement of continental weathering. The enhanced
      continental weathering delivered excessive nutrients to the oceans that could
      lead to marine eutrophication, anoxia, acidification, and ecological
      perturbation, ultimately resulting in the end-Permian mass extinction.

PMID- 29581277
TI  - Endoplasmic reticulum-localized CCX2 is required for osmotolerance by regulating
      ER and cytosolic Ca2+ dynamics in Arabidopsis.
AB  - Ca2+ signals in plant cells are important for adaptive responses to environmental
      stresses. Here, we report that the Arabidopsis CATION/Ca2+ EXCHANGER2 (CCX2),
      encoding a putative cation/Ca2+ exchanger that localizes to the endoplasmic
      reticulum (ER), is strongly induced by salt and osmotic stresses. Compared with
      the WT, AtCCX2 loss-of-function mutant was less tolerant to osmotic stress and
      displayed the most noteworthy phenotypes (less root/shoot growth) during salt
      stress. Conversely, AtCCX2 gain-of-function mutants were more tolerant to osmotic
      stress. In addition, AtCCX2 partially suppresses the Ca2+ sensitivity of K667
      yeast triple mutant, characterized by Ca2+ uptake deficiency. Remarkably,
      Cameleon Ca2+ sensors revealed that the absence of AtCCX2 activity results in
      decreased cytosolic and increased ER Ca2+ concentrations in comparison with both
      WT and the gain-of-function mutants. This was observed in both salt and nonsalt
      osmotic stress conditions. It appears that AtCCX2 is directly involved in the
      control of Ca2+ fluxes between the ER and the cytosol, which plays a key role in
      the ability of plants to cope with osmotic stresses. To our knowledge, Atccx2 is
      unique as a plant mutant to show a measured alteration in ER Ca2+ concentrations.
      In this study, we identified the ER-localized AtCCX2 as a pivotal player in the
      regulation of ER Ca2+ dynamics that heavily influence plant growth upon salt and
      osmotic stress.

PMID- 29581279
TI  - Reduction of lipid accumulation rescues Bietti's crystalline dystrophy
      phenotypes.
AB  - Bietti's crystalline dystrophy (BCD) is an intractable and progressive
      chorioretinal degenerative disease caused by mutations in the CYP4V2 gene,
      resulting in blindness in most patients. Although we and others have shown that
      retinal pigment epithelium (RPE) cells are primarily impaired in patients with
      BCD, the underlying mechanisms of RPE cell damage are still unclear because we
      lack access to appropriate disease models and to lesion-affected cells from
      patients with BCD. Here, we generated human RPE cells from induced pluripotent
      stem cells (iPSCs) derived from patients with BCD carrying a CYP4V2 mutation and
      successfully established an in vitro model of BCD, i.e., BCD patient-specific
      iPSC-RPE cells. In this model, RPE cells showed degenerative changes of
      vacuolated cytoplasm similar to those in postmortem specimens from patients with
      BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of
      autophagy flux, followed by cell death. Lipidomic analyses revealed the
      accumulation of glucosylceramide and free cholesterol in BCD-affected cells.
      Notably, we found that reducing free cholesterol by cyclodextrins or delta
      tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide
      reduction did not affect the BCD phenotype. Our data provide evidence that
      reducing intracellular free cholesterol may have therapeutic efficacy in patients
      with BCD.

PMID- 29581281
TI  - Water-like anomalies as a function of tetrahedrality.
AB  - Tetrahedral interactions describe the behavior of the most abundant and
      technologically important materials on Earth, such as water, silicon, carbon,
      germanium, and countless others. Despite their differences, these materials share
      unique common physical behaviors, such as liquid anomalies, open crystalline
      structures, and extremely poor glass-forming ability at ambient pressure. To
      reveal the physical origin of these anomalies and their link to the shape of the
      phase diagram, we systematically study the properties of the Stillinger-Weber
      potential as a function of the strength of the tetrahedral interaction [Formula:
      see text] We uncover a unique transition to a reentrant spinodal line at low
      values of [Formula: see text], accompanied with a change in the dynamical
      behavior, from non-Arrhenius to Arrhenius. We then show that a two-state model
      can provide a comprehensive understanding on how the thermodynamic and dynamic
      anomalies of this important class of materials depend on the strength of the
      tetrahedral interaction. Our work establishes a deep link between the shape of
      the phase diagram and the thermodynamic and dynamic properties through local
      structural ordering in liquids and hints at why water is so special among all
      substances.

PMID- 29581282
TI  - Profile of Dorothy L. Cheney and Robert M. Seyfarth.

PMID- 29581280
TI  - Chloroplast SRP43 acts as a chaperone for glutamyl-tRNA reductase, the rate
      limiting enzyme in tetrapyrrole biosynthesis.
AB  - Assembly of light-harvesting complexes requires synchronization of chlorophyll
      (Chl) biosynthesis with biogenesis of light-harvesting Chl a/b-binding proteins
      (LHCPs). The chloroplast signal recognition particle (cpSRP) pathway is
      responsible for transport of nucleus-encoded LHCPs in the stroma of the plastid
      and their integration into the thylakoid membranes. Correct folding and assembly
      of LHCPs require the incorporation of Chls, whose biosynthesis must therefore be
      precisely coordinated with membrane insertion of LHCPs. How the spatiotemporal
      coordination between the cpSRP machinery and Chl biosynthesis is achieved is
      poorly understood. In this work, we demonstrate a direct interaction between
      cpSRP43, the chaperone that mediates LHCP targeting and insertion, and glutamyl
      tRNA reductase (GluTR), a rate-limiting enzyme in tetrapyrrole biosynthesis.
      Concurrent deficiency for cpSRP43 and the GluTR-binding protein (GBP) additively
      reduces GluTR levels, indicating that cpSRP43 and GBP act nonredundantly to
      stabilize GluTR. The substrate-binding domain of cpSRP43 binds to the N-terminal
      region of GluTR, which harbors aggregation-prone motifs, and the chaperone
      activity of cpSRP43 efficiently prevents aggregation of these regions. Our work
      thus reveals a function of cpSRP43 in Chl biosynthesis and suggests a striking
      mechanism for posttranslational coordination of LHCP insertion with Chl
      biosynthesis.

PMID- 29581283
TI  - Dependence of the evolution of carbon dynamics in the northern permafrost region
      on the trajectory of climate change.
AB  - We conducted a model-based assessment of changes in permafrost area and carbon
      storage for simulations driven by RCP4.5 and RCP8.5 projections between 2010 and
      2299 for the northern permafrost region. All models simulating carbon represented
      soil with depth, a critical structural feature needed to represent the permafrost
      carbon-climate feedback, but that is not a universal feature of all climate
      models. Between 2010 and 2299, simulations indicated losses of permafrost between
      3 and 5 million km2 for the RCP4.5 climate and between 6 and 16 million km2 for
      the RCP8.5 climate. For the RCP4.5 projection, cumulative change in soil carbon
      varied between 66-Pg C (1015-g carbon) loss to 70-Pg C gain. For the RCP8.5
      projection, losses in soil carbon varied between 74 and 652 Pg C (mean loss, 341
      Pg C). For the RCP4.5 projection, gains in vegetation carbon were largely
      responsible for the overall projected net gains in ecosystem carbon by 2299 (8-
      to 244-Pg C gains). In contrast, for the RCP8.5 projection, gains in vegetation
      carbon were not great enough to compensate for the losses of carbon projected by
      four of the five models; changes in ecosystem carbon ranged from a 641-Pg C loss
      to a 167-Pg C gain (mean, 208-Pg C loss). The models indicate that substantial
      net losses of ecosystem carbon would not occur until after 2100. This assessment
      suggests that effective mitigation efforts during the remainder of this century
      could attenuate the negative consequences of the permafrost carbon-climate
      feedback.

PMID- 29581284
TI  - Light-induced dilation in nanosheets of charge-transfer complexes.
AB  - We report the observation of a sizable photostrictive effect of 5.7% with fast,
      submillisecond response times, arising from a light-induced lattice dilation of a
      molecular nanosheet, composed of the molecular charge-transfer compound
      dibenzotetrathiafulvalene (DBTTF) and C60 An interfacial self-assembly approach
      is introduced for the thickness-controlled growth of the thin films. From
      photoabsorption measurements, molecular simulations, and electronic structure
      calculations, we suggest that photostriction within these films arises from a
      transformation in the molecular structure of constituent molecules upon
      photoinduced charge transfer, as well as the accommodation of free charge
      carriers within the material. Additionally, we find that the photostrictive
      properties of the nanosheets are thickness-dependent, a phenomenon that we
      suggest arises from surface-induced conformational disorder in the molecular
      components of the film. Moreover, because of the molecular structure in the
      films, which results largely from interactions between the constituent pi-systems
      and the sulfur atoms of DBTTF, the optoelectronic properties are found to be
      anisotropic. This work enables the fabrication of 2D molecular charge-transfer
      nanosheets with tunable thicknesses and properties, suitable for a wide range of
      applications in flexible electronic technologies.

PMID- 29581285
TI  - Water-mediated conformational preselection mechanism in substrate binding
      cooperativity to protein kinase A.
AB  - Substrate binding cooperativity in protein kinase A (PKA) seems to involve
      allosteric coupling between the two binding sites. It received significant
      attention, but its molecular basis still remains not entirely clear. Based on
      long molecular dynamics of PKA and its complexes, we characterized an allosteric
      pathway that links ATP binding to the redistribution of states adopted by a
      protein substrate positioning segment in favor of those that warrant correct
      binding. We demonstrate that the cooperativity mechanism critically depends on
      the presence of water in two distinct, buried hydration sites. One holds just a
      single water molecule, which acts as a switchable hydrogen bond bridge along the
      allosteric pathway. The second, filled with partially disordered solvent, is
      essential for providing a smooth free energy landscape underlying conformational
      transitions of the peptide binding region. Our findings remain in agreement with
      experimental data, also concerning the cooperativity abolishing effect of the
      Y204A mutation, and indicate a plausible molecular mechanism contributing to
      experimentally observed binding cooperativity of the two substrates.

PMID- 29581286
TI  - Embryophyte stress signaling evolved in the algal progenitors of land plants.
AB  - Streptophytes are unique among photosynthetic eukaryotes in having conquered
      land. As the ancestors of land plants, streptophyte algae are hypothesized to
      have possessed exaptations to the environmental stressors encountered during the
      transition to terrestrial life. Many of these stressors, including high
      irradiance and drought, are linked to plastid biology. We have investigated
      global gene expression patterns across all six major streptophyte algal lineages,
      analyzing a total of around 46,000 genes assembled from a little more than 1.64
      billion sequence reads from six organisms under three growth conditions. Our
      results show that streptophyte algae respond to cold and high light stress via
      expression of hallmark genes used by land plants (embryophytes) during stress
      response signaling and downstream responses. Among the strongest differentially
      regulated genes were those associated with plastid biology. We observed that
      among streptophyte algae, those most closely related to land plants, especially
      Zygnema, invest the largest fraction of their transcriptional budget in plastid
      targeted proteins and possess an array of land plant-type plastid-nucleus
      communication genes. Streptophyte algae more closely related to land plants also
      appear most similar to land plants in their capacity to respond to plastid
      stressors. Support for this notion comes from the detection of a canonical
      abscisic acid receptor of the PYRABACTIN RESISTANCE (PYR/PYL/RCAR) family in
      Zygnema, the first found outside the land plant lineage. We conclude that a fine
      tuned response toward terrestrial plastid stressors was among the exaptations
      that allowed streptophytes to colonize the terrestrial habitat on a global scale.

PMID- 29581287
TI  - Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle
      regeneration.
AB  - Regeneration of skeletal muscle in response to injury occurs through fusion of a
      population of stem cells, known as satellite cells, with injured myofibers.
      Myomixer, a muscle-specific membrane micropeptide, cooperates with the
      transmembrane protein Myomaker to regulate embryonic myoblast fusion and muscle
      formation. To investigate the role of Myomixer in muscle regeneration, we used
      CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer
      alleles in mice. We show that genetic deletion of Myomixer in satellite cells
      using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7
      promoter abolishes satellite cell fusion and prevents muscle regeneration,
      resulting in severe muscle degeneration after injury. Satellite cells devoid of
      Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is
      insufficient to drive myoblast fusion. These findings, together with prior
      studies demonstrating the essentiality of Myomaker for muscle regeneration,
      highlight the obligatory partnership of Myomixer and Myomaker for myofiber
      formation throughout embryogenesis and adulthood.

PMID- 29581288
TI  - Small proline-rich protein 2B drives stress-dependent p53 degradation and
      fibroblast proliferation in heart failure.
AB  - Heart disease is associated with the accumulation of resident cardiac fibroblasts
      (CFs) that secrete extracellular matrix (ECM), leading to the development of
      pathological fibrosis and heart failure. However, the mechanisms underlying
      resident CF proliferation remain poorly defined. Here, we report that small
      proline-rich protein 2b (Sprr2b) is among the most up-regulated genes in CFs
      during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the
      USP7/MDM2-containing ubiquitination complex. SPRR2B stimulates the accumulation
      of MDM2 and the degradation of p53, thus facilitating the proliferation of
      pathological CFs. Furthermore, SPRR2B phosphorylation by nonreceptor tyrosine
      kinases in response to TGF-beta1 signaling and free-radical production
      potentiates SPRR2B activity and cell cycle progression. Knockdown of the Sprr2b
      gene or inhibition of SPRR2B phosphorylation attenuates USP7/MDM2 binding and p53
      degradation, leading to CF cell cycle arrest. Importantly, SPRR2B expression is
      elevated in cardiac tissue from human heart failure patients and correlates with
      the proliferative state of patient-derived CFs in a process that is reversed by
      insulin growth factor-1 signaling. These data establish SPRR2B as a unique
      component of the USP7/MDM2 ubiquitination complex that drives p53 degradation, CF
      accumulation, and the development of pathological cardiac fibrosis.

PMID- 29581289
TI  - Energetic tradeoffs control the size distribution of aquatic mammals.
AB  - Four extant lineages of mammals have invaded and diversified in the water:
      Sirenia, Cetacea, Pinnipedia, and Lutrinae. Most of these aquatic clades are
      larger bodied, on average, than their closest land-dwelling relatives, but the
      extent to which potential ecological, biomechanical, and physiological controls
      contributed to this pattern remains untested quantitatively. Here, we use
      previously published data on the body masses of 3,859 living and 2,999 fossil
      mammal species to examine the evolutionary trajectories of body size in aquatic
      mammals through both comparative phylogenetic analysis and examination of the
      fossil record. Both methods indicate that the evolution of an aquatic lifestyle
      is driving three of the four extant aquatic mammal clades toward a size attractor
      at ~500 kg. The existence of this body size attractor and the relatively rapid
      selection toward, and limited deviation from, this attractor rule out most
      hypothesized drivers of size increase. These three independent body size
      increases and a shared aquatic optimum size are consistent with control by
      differences in the scaling of energetic intake and cost functions with body size
      between the terrestrial and aquatic realms. Under this energetic model,
      thermoregulatory costs constrain minimum size, whereas limitations on feeding
      efficiency constrain maximum size. The optimum size occurs at an intermediate
      value where thermoregulatory costs are low but feeding efficiency remains high.
      Rather than being released from size pressures, water-dwelling mammals are driven
      and confined to larger body sizes by the strict energetic demands of the aquatic
      medium.

PMID- 29581290
TI  - OSR1 regulates a subset of inward rectifier potassium channels via a binding
      motif variant.
AB  - The with-no-lysine (K) (WNK) signaling pathway to STE20/SPS1-related proline- and
      alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) kinase is an
      important mediator of cell volume and ion transport. SPAK and OSR1 associate with
      upstream kinases WNK 1-4, substrates, and other proteins through their C-terminal
      domains which interact with linear R-F-x-V/I sequence motifs. In this study we
      find that SPAK and OSR1 also interact with similar affinity with a motif variant,
      R-x-F-x-V/I. Eight of 16 human inward rectifier K+ channels have an R-x-F-x-V
      motif. We demonstrate that two of these channels, Kir2.1 and Kir2.3, are
      activated by OSR1, while Kir4.1, which does not contain the motif, is not
      sensitive to changes in OSR1 or WNK activity. Mutation of the motif prevents
      activation of Kir2.3 by OSR1. Both siRNA knockdown of OSR1 and chemical
      inhibition of WNK activity disrupt NaCl-induced plasma membrane localization of
      Kir2.3. Our results suggest a mechanism by which WNK-OSR1 enhance Kir2.1 and
      Kir2.3 channel activity by increasing their plasma membrane localization.
      Regulation of members of the inward rectifier K+ channel family adds functional
      and mechanistic insight into the physiological impact of the WNK pathway.

PMID- 29581291
TI  - Divergent trends of open-surface water body area in the contiguous United States
      from 1984 to 2016.
AB  - The contiguous United States (CONUS), especially the West, faces challenges of
      increasing water stress and uncertain impacts of climate change. The historical
      information of surface water body distribution, variation, and multidecadal
      trends documented in remote-sensing images can aid in water-resource planning and
      management, yet is not well explored. Here, we detected open-surface water bodies
      in all Landsat 5, 7, and 8 images (~370,000 images, >200 TB) of the CONUS and
      generated 30-meter annual water body frequency maps for 1984-2016. We analyzed
      the interannual variations and trends of year-long water body area, examined the
      impacts of climatic and anthropogenic drivers on water body area dynamics, and
      explored the relationships between water body area and land water storage (LWS).
      Generally, the western half of the United States is prone to water stress, with
      small water body area and large interannual variability. During 1984-2016, water
      poor regions of the Southwest and Northwest had decreasing trends in water body
      area, while water-rich regions of the Southeast and far north Great Plains had
      increasing trends. These divergent trends, mainly driven by climate, enlarged
      water-resource gaps and are likely to continue according to climate projections.
      Water body area change is a good indicator of LWS dynamics in 58% of the CONUS.
      Following the 2012 prolonged drought, LWS in California and the southern Great
      Plains had a larger decrease than surface water body area, likely caused by
      massive groundwater withdrawals. Our findings provide valuable information for
      surface water-resource planning and management across the CONUS.

PMID- 29581292
TI  - Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in
      beta-arrestin coupling.
AB  - The ability of G protein-coupled receptors (GPCRs) to initiate complex cascades
      of cellular signaling is governed by the sequential coupling of three main
      transducer proteins, G protein, GPCR kinase (GRK), and beta-arrestin. Mounting
      evidence indicates these transducers all have distinct conformational preferences
      and binding modes. However, interrogating each transducer's mechanism of
      interaction with GPCRs has been complicated by the interplay of transducer
      mediated signaling events. For example, GRK-mediated receptor phosphorylation
      recruits and induces conformational changes in beta-arrestin, which facilitates
      coupling to the GPCR transmembrane core. Here we compare the allosteric
      interactions of G proteins and beta-arrestins with GPCRs' transmembrane cores by
      using the enzyme sortase to ligate a synthetic phosphorylated peptide onto the
      carboxyl terminus of three different receptors. Phosphopeptide ligation onto the
      beta2-adrenergic receptor (beta2AR) allows stabilization of a high-affinity
      receptor active state by beta-arrestin1, permitting us to define elements in the
      beta2AR and beta-arrestin1 that contribute to the receptor transmembrane core
      interaction. Interestingly, ligation of the identical phosphopeptide onto the
      beta2AR, the muscarinic acetylcholine receptor 2 and the MU-opioid receptor
      reveals that the ability of beta-arrestin1 to enhance agonist binding relative to
      G protein differs substantially among receptors. Furthermore, strong allosteric
      coupling of beta-arrestin1 correlates with its ability to attenuate, or
      "desensitize," G protein activation in vitro. Sortase ligation thus provides a
      versatile method to introduce complex, defined phosphorylation patterns into
      GPCRs, and analogous strategies could be applied to other classes of
      posttranslationally modified proteins. These homogeneously phosphorylated GPCRs
      provide an innovative means to systematically study receptor-transducer
      interactions.

PMID- 29581293
TI  - South American monsoon response to iceberg discharge in the North Atlantic.
AB  - Heinrich Stadials significantly affected tropical precipitation through changes
      in the interhemispheric temperature gradient as a result of abrupt cooling in the
      North Atlantic. Here, we focus on changes in South American monsoon precipitation
      during Heinrich Stadials using a suite of speleothem records covering the last 85
      ky B.P. from eastern South America. We document the response of South American
      monsoon precipitation to episodes of extensive iceberg discharge, which is
      distinct from the response to the cooling episodes that precede the main phase of
      ice-rafted detritus deposition. Our results demonstrate that iceberg discharge in
      the western subtropical North Atlantic led to an abrupt increase in monsoon
      precipitation over eastern South America. Our findings of an enhanced Southern
      Hemisphere monsoon, coeval with the iceberg discharge into the North Atlantic,
      are consistent with the observed abrupt increase in atmospheric methane
      concentrations during Heinrich Stadials.

PMID- 29581294
TI  - Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.
AB  - Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) 
      dependent amine oxidase, catalyze the oxidative deamination of lysine residues of
      extracellular matrix (ECM) proteins such as elastins and collagens and generate
      aldehyde groups. The oxidative deamination of lysine represents the foundational
      step for the cross-linking of elastin and collagen and thus is crucial for ECM
      modeling. Despite their physiological significance, the structure of this
      important family of enzymes remains elusive. Here we report the crystal structure
      of human lysyl oxidase-like 2 (hLOXL2) at 2.4-A resolution. Unexpectedly, the
      copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation
      and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis
      confirms that copper loading robustly activates hLOXL2 and supports LTQ
      formation. Furthermore, the LTQ precursor residues in the structure are distanced
      by 16.6 A, corroborating the notion that the present structure may represent a
      precursor state and that pronounced conformational rearrangements would be
      required for protein activation. The structure presented here establishes an
      important foundation for understanding the structure-function relationship of LOX
      proteins and will facilitate LOX-targeting drug discovery.

PMID- 29581295
TI  - Amide-forming chemical ligation via O-acyl hydroxamic acids.
AB  - The facile rearrangement of "S-acyl isopeptides" to native peptide bonds via S,N
      acyl shift is central to the success of native chemical ligation, the widely used
      approach for protein total synthesis. Proximity-driven amide bond formation via
      acyl transfer reactions in other contexts has proven generally less effective.
      Here, we show that under neutral aqueous conditions, "O-acyl isopeptides" derived
      from hydroxy-asparagine [aspartic acid-beta-hydroxamic acid; Asp(beta-HA)]
      rearrange to form native peptide bonds via an O,N-acyl shift. This process
      constitutes a rare example of an O,N-acyl shift that proceeds rapidly across a
      medium-size ring (t1/2 ~ 15 min), and takes place in water with minimal
      interference from hydrolysis. In contrast to serine/threonine or tyrosine, which
      form O-acyl isopeptides only by the use of highly activated acyl donors and
      appropriate protecting groups in organic solvent, Asp(beta-HA) is sufficiently
      reactive to form O-acyl isopeptides by treatment with an unprotected peptide
      alphathioester, at low mM concentration, in water. These findings were applied to
      an acyl transfer-based chemical ligation strategy, in which an unprotected N
      terminal Asp(beta-HA)-peptide and peptide-alphathioester react under aqueous
      conditions to give a ligation product ultimately linked by a native peptide bond.

PMID- 29581296
TI  - Recombinant immunotoxins with albumin-binding domains have long half-lives and
      high antitumor activity.
AB  - Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that
      binds to a cancer cell and a portion of a protein toxin. One of these,
      Moxetumomab pasudotox, was shown to be effective in treating patients with some
      leukemias, where the cells are readily accessible to the RIT. However, their
      short half-life limits their efficacy in solid tumors, because penetration into
      the tumors is slow. Albumin and agents bound to albumin have a long half-life in
      the circulation. To increase the time tumor cells are exposed to RITs, we have
      produced and evaluated variants that contain either an albumin-binding domain
      (ABD) from Streptococcus or single-domain antibodies from Llama. We have inserted
      these ABDs into RITs targeting mesothelin, between the Fv and the furin cleavage
      site. We find that these proteins can be produced in large amounts, are very
      cytotoxic to mesothelin-expressing cancer cell lines, and have a high affinity
      for human or mouse serum albumin. In mice, the RIT containing an ABD from
      Streptococcus has a longer half-life and higher antitumor activity than the other
      two. Its half-life in the circulation of mice ranges from 113 to 194 min compared
      with 13 min for an RIT with no ABD. Cell uptake studies show the RIT enters the
      target cell bound to serum albumin. We conclude that RITs with improved half
      lives and antitumor activity should be evaluated for the treatment of cancer in
      humans.

PMID- 29581297
TI  - Inhibition of Enhancer of zeste homolog 2 (EZH2) induces natural killer cell
      mediated eradication of hepatocellular carcinoma cells.
AB  - Natural killer (NK) cell-mediated tumor cell eradication could inhibit tumor
      initiation and progression. However, the factors that regulate NK cell-mediated
      cancer cell eradication remain unclear. We determined that hepatocellular
      carcinoma (HCC) cells exhibit transcriptional down-regulation of NK group 2D
      (NKG2D) ligands and are largely resistant to NK cell-mediated eradication.
      Because the down-regulation of NKG2D ligands occurred at the transcriptional
      level, we tested 32 chemical inhibitors of epigenetic regulators for their
      ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells
      and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor
      of NKG2D ligands. The inhibition of EZH2 by small-molecule inhibitors or genetic
      means enhanced HCC cell eradication by NK cells in a NKG2D ligand-dependent
      manner. Collectively, these results demonstrate that EZH2 inhibition enhances HCC
      eradication by NK cells and that EZH2 functions, in part, as an oncogene by
      inhibiting immune response.

PMID- 29581298
TI  - RNA-mediated gene regulation is less evolvable than transcriptional regulation.
AB  - Much of gene regulation is carried out by proteins that bind DNA or RNA molecules
      at specific sequences. One class of such proteins is transcription factors, which
      bind short DNA sequences to regulate transcription. Another class is RNA binding
      proteins, which bind short RNA sequences to regulate RNA maturation, transport,
      and stability. Here, we study the robustness and evolvability of these regulatory
      mechanisms. To this end, we use experimental binding data from 172 human and
      fruit fly transcription factors and RNA binding proteins as well as human
      polymorphism data to study the evolution of binding sites in vivo. We find little
      difference between the robustness of regulatory protein-RNA interactions and
      transcription factor-DNA interactions to DNA mutations. In contrast, we find that
      RNA-mediated regulation is less evolvable than transcriptional regulation,
      because mutations are less likely to create interactions of an RNA molecule with
      a new RNA binding protein than they are to create interactions of a gene
      regulatory region with a new transcription factor. Our observations are
      consistent with the high level of conservation observed for interactions between
      RNA binding proteins and their target molecules as well as the evolutionary
      plasticity of regulatory regions bound by transcription factors. They may help
      explain why transcriptional regulation is implicated in many more evolutionary
      adaptations and innovations than RNA-mediated gene regulation.

PMID- 29581299
TI  - MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis.
AB  - The MDM2 homolog MDMX oncoprotein is indispensable for inhibition of p53 during
      normal embryonic development and malignant transformation, yet how MDMX harnesses
      p53 functions is unclear. In addition to a canonical N-terminal p53-binding
      domain, recent work suggests the central acidic domain of MDMX regulates p53
      interaction through intramolecular mimicry and engages in second-site interaction
      with the p53 core domain in vitro. To test the physiological relevance of these
      interactions, we generated an MDMX knockin mouse having substitutions in a
      conserved WW motif necessary for these functions (W201S/W202G). Notably, MDMXSG
      cells have normal p53 level but increased p53 DNA binding and target gene
      expression, and rapidly senesce. In vivo, MDMXSG inhibits early-phase disease in
      Eu-Myc transgenic mice but accelerates the onset of lethal lymphoma and shortens
      overall survival. Therefore, MDMX is an important regulator of p53 DNA binding,
      which complements the role of MDM2 in regulating p53 level. Furthermore, the
      results suggest that the WW motif has dual functions that regulate p53 and
      inhibit Myc-driven lymphomas independent of p53.

PMID- 29581301
TI  - Escalation of competition into conflict in competitive networks of Formula One
      drivers.
AB  - This article investigates the factors that escalate competition into dangerous
      conflict. Recent sociological theorizing claims that such escalations are
      particularly likely in dyads of structurally equivalent people (i.e., actors who
      have the same relations with the same third parties). Using panel data on Formula
      One races from 1970 through 2014, we model the probability that two drivers
      collide on the racetrack (an observable trace of conflict) as a function of their
      structural equivalence in a dynamic network of competitive relationships. Our
      main hypothesis, that the likelihood of conflict rises with structural
      equivalence, receives empirical support. Our findings also show that the positive
      association between structural equivalence and conflict is neither merely a
      matter of contention for official position nor an artifact of inherently hostile
      parties spatially exposed to each other. Our analyses further reveal that this
      positive association is concentrated in a number of theoretically predictable
      conditions: among age-similar dyads, among stronger performers, in stable
      competitive networks, and in safe, rather than dangerous, weather conditions.
      Implications for future research on conflict, networks, and tournaments are
      discussed.

PMID- 29581300
TI  - BACE1 SUMOylation increases its stability and escalates the protease activity in
      Alzheimer's disease.
AB  - Amyloid beta (Abeta) is a major pathological marker in Alzheimer's disease (AD),
      which is principally regulated by the rate-limiting beta-secretase (i.e., BACE1)
      cleavage of amyloid precursor protein (APP). However, how BACE1 activity is
      posttranslationally regulated remains incompletely understood. Here, we show that
      BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease
      activity and stability and subsequently increases Abeta production, leading to
      cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R
      mutant, injection of wild-type BACE1 significantly increases Abeta production and
      triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1,
      but not non-SUMOylated K501R mutant, facilitates senile plaque formation and
      aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together,
      our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in
      mediating its stability and enzymatic activity.

PMID- 29581302
TI  - New tRNA contacts facilitate ligand binding in a Mycobacterium smegmatis T box
      riboswitch.
AB  - T box riboswitches are RNA regulatory elements widely used by organisms in the
      phyla Firmicutes and Actinobacteria to regulate expression of amino acid-related
      genes. Expression of T box family genes is down-regulated by transcription
      attenuation or inhibition of translation initiation in response to increased
      charging of the cognate tRNA. Three direct contacts with tRNA have been
      described; however, one of these contacts is absent in a subclass of T box RNAs
      and the roles of several structural domains conserved in most T box RNAs are
      unknown. In this study, structural elements of a Mycobacterium smegmatis ileS T
      box riboswitch variant with an Ultrashort (US) Stem I were sequentially deleted,
      which resulted in a progressive decrease in binding affinity for the tRNAIle
      ligand. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE)
      revealed structural changes in conserved riboswitch domains upon interaction with
      the tRNA ligand. Cross-linking and mutational analyses identified two interaction
      sites, one between the S-turn element in Stem II and the T arm of tRNAIle and the
      other between the Stem IIA/B pseudoknot and the D loop of tRNAIle These newly
      identified RNA contacts add information about tRNA recognition by the T box
      riboswitch and demonstrate a role for the S-turn and pseudoknot elements, which
      resemble structural elements that are common in many cellular RNAs.

PMID- 29581303
TI  - Structural basis for the ethanol action on G-protein-activated inwardly
      rectifying potassium channel 1 revealed by NMR spectroscopy.
AB  - Ethanol consumption leads to a wide range of pharmacological effects by acting on
      the signaling proteins in the human nervous system, such as ion channels. Despite
      its familiarity and biological importance, very little is known about the
      molecular mechanisms underlying the ethanol action, due to extremely weak binding
      affinity and the dynamic nature of the ethanol interaction. In this research, we
      focused on the primary in vivo target of ethanol, G-protein-activated inwardly
      rectifying potassium channel (GIRK), which is responsible for the ethanol-induced
      analgesia. By utilizing solution NMR spectroscopy, we characterized the changes
      in the structure and dynamics of GIRK induced by ethanol binding. We demonstrated
      here that ethanol binds to GIRK with an apparent dissociation constant of 1.0 M
      and that the actual physiological binding site of ethanol is located on the
      cavity formed between the neighboring cytoplasmic regions of the GIRK tetramer.
      From the methyl-based NMR relaxation analyses, we revealed that ethanol activates
      GIRK by shifting the conformational equilibrium processes, which are responsible
      for the gating of GIRK, to stabilize an open conformation of the cytoplasmic ion
      gate. We suggest that the dynamic molecular mechanism of the ethanol-induced
      activation of GIRK represents a general model of the ethanol action on signaling
      proteins in the human nervous system.

PMID- 29581304
TI  - Identifying psychological responses of stigmatized groups to referendums.
AB  - Public votes and referendums on the rights of marginalized communities are
      utilized in 27 states and occur with some regularity. However, research has only
      recently begun to examine the psychological consequences of these voter
      referendums for members of stigmatized groups, and a number of important
      questions remain regarding the internal validity and generalizability of the
      existing evidence. The current study advances this literature by combining survey
      data from a large probability-based sample conducted in 2012 [lesbian, gay,
      bisexual, and/or transgender (LGBT) n = 939; non-LGBT n = 31,067] with media
      market ad-buy data in states where marriage equality was on the ballot.
      Television media markets cross state boundaries, ensuring that there was an
      unintended group of people in 12 states who were exposed to the same-sex marriage
      discourse but who did not live in states with the voter referendum ("media market
      spillovers"). We take advantage of this unique data structure by comparing LGBT
      people in the media market spillovers to those residing in the same state but in
      nonspillover markets with no ad exposure. LGBT people are emotionally affected by
      these campaigns, and non-LGBT people are unaffected. LGBT people in markets with
      a cumulative total of 400 ads have a 34.0% greater probability of reporting
      stress than LGBT people not exposed to ads. Additionally, while the negative ads
      evoked sadness, positive ads evoked enjoyment and happiness. Thus, public votes
      on minority rights represent both a source of minority stress and resilience.

PMID- 29581305
TI  - Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts.
AB  - LMNA encodes the A-type lamins that are part of the nuclear scaffold. Mutations
      in LMNA can cause a variety of disorders called laminopathies, including
      Hutchinson-Gilford progeria syndrome (HGPS), atypical Werner syndrome, and Emery
      Dreifuss muscular dystrophy. Previous work has shown that treatment of HGPS cells
      with the mTOR inhibitor rapamycin or with the rapamycin analog everolimus
      corrects several of the phenotypes seen at the cellular level-at least in part by
      increasing autophagy and reducing the amount of progerin, the toxic form of lamin
      A that is overproduced in HGPS patients. Since other laminopathies also result in
      production of abnormal and potentially toxic lamin proteins, we hypothesized that
      everolimus would also be beneficial in those disorders. To test this, we applied
      everolimus to fibroblast cell lines from six laminopathy patients, each with a
      different mutation in LMNA Everolimus treatment increased proliferative ability
      and delayed senescence in all cell lines. In several cell lines, we observed that
      with treatment, there is a significant improvement in nuclear blebbing, which is
      a cellular hallmark of HGPS and other lamin disorders. These preclinical results
      suggest that everolimus might have clinical benefit for multiple laminopathy
      syndromes.

PMID- 29581306
TI  - Cross-linking of Orai1 channels by STIM proteins.
AB  - The transmembrane docking of endoplasmic reticulum (ER) Ca2+-sensing STIM
      proteins with plasma membrane (PM) Orai Ca2+ channels is a critical but poorly
      understood step in Ca2+ signal generation. STIM1 protein dimers unfold to expose
      a discrete STIM-Orai activating region (SOAR1) that tethers and activates Orai1
      channels within discrete ER-PM junctions. We reveal that each monomer within the
      SOAR dimer interacts independently with single Orai1 subunits to mediate cross
      linking between Orai1 channels. Superresolution imaging and mobility measured by
      fluorescence recovery after photobleaching reveal that SOAR dimer cross-linking
      leads to substantial Orai1 channel clustering, resulting in increased efficacy
      and cooperativity of Orai1 channel function. A concatenated SOAR1 heterodimer
      containing one monomer point mutated at its critical Orai1 binding residue
      (F394H), although fully activating Orai channels, is completely defective in
      cross-linking Orai1 channels. Importantly, the naturally occurring STIM2 variant,
      STIM2.1, has an eight-amino acid insert in its SOAR unit that renders it
      functionally identical to the F394H mutant in SOAR1. Contrary to earlier
      predictions, the SOAR1-SOAR2.1 heterodimer fully activates Orai1 channels but
      prevents cross-linking and clustering of channels. Interestingly, combined
      expression of full-length STIM1 with STIM2.1 in a 5:1 ratio causes suppression of
      sustained agonist-induced Ca2+ oscillations and protects cells from Ca2+
      overload, resulting from high agonist-induced Ca2+ release. Thus, STIM2.1 exerts
      a powerful regulatory effect on signal generation likely through preventing Orai1
      channel cross-linking. Overall, STIM-mediated cross-linking of Orai1 channels is
      a hitherto unrecognized functional paradigm that likely provides an
      organizational microenvironment within ER-PM junctions with important functional
      impact on Ca2+ signal generation.

PMID- 29581308
TI  - Split cGAL, an intersectional strategy using a split intein for refined
      spatiotemporal transgene control in Caenorhabditis elegans.
AB  - Bipartite expression systems, such as the GAL4-UAS system, allow fine
      manipulation of gene expression and are powerful tools for interrogating gene
      function. Recently, we established cGAL, a GAL4-based bipartite expression system
      for transgene control in Caenorhabditis elegans, where a single promoter dictates
      the expression pattern of a cGAL driver, which then binds target upstream
      activation sequences to drive expression of a downstream effector gene. Here, we
      report a split strategy for cGAL using the split intein gp41-1 for intersectional
      control of transgene expression. Split inteins are protein domains that
      associate, self-excise, and covalently ligate their flanking peptides together.
      We split the DNA binding domain and transcriptional activation domain of cGAL and
      fused them to the N terminal of gp41-1-N-intein and the C terminal of gp41-1-C
      intein, respectively. In cells where both halves of cGAL are expressed, a
      functional cGAL driver is reconstituted via intein-mediated protein splicing.
      This reconstitution allows expression of the driver to be dictated by two
      promoters for refined spatial control or spatiotemporal control of transgene
      expression. We apply the split cGAL system to genetically access the single pair
      of MC neurons (previously inaccessible with a single promoter), and reveal an
      important role of protein kinase A in rhythmic pharyngeal pumping in C. elegans
      Thus, the split cGAL system gives researchers a greater degree of spatiotemporal
      control over transgene expression, and will be a valuable genetic tool in C.
      elegans for dissecting gene function with finer cell-specific resolution.

PMID- 29581307
TI  - Structural determinants and cellular environment define processed actin as the
      sole substrate of the N-terminal acetyltransferase NAA80.
AB  - N-terminal (Nt) acetylation is a major protein modification catalyzed by N
      terminal acetyltransferases (NATs). Methionine acidic N termini, including actin,
      are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins
      containing acidic N termini, are additionally posttranslationally Nt acetylated
      by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and
      motility, thus making NAA80 a potential target for cell migration regulation. In
      this work, we developed potent and selective bisubstrate inhibitors for NAA80 and
      determined the crystal structure of NAA80 in complex with such an inhibitor,
      revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more
      open substrate binding region. Furthermore, in contrast to most other NATs, the
      substrate specificity of NAA80 is mainly derived through interactions between the
      enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and
      not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in
      a strain lacking NatB activity partially restored Nt acetylation of NatB
      substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to
      posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the
      presence of a dominant cotranslational NatB in all eukaryotes, the specific
      posttranslational actin methionine removal in animals, and finally, the unique
      structural features of NAA80 leave only the processed actins as in vivo
      substrates of NAA80. Together, this study reveals the molecular and cellular
      basis of NAA80 Nt acetylation and provides a scaffold for development of
      inhibitors for the regulation of cytoskeletal properties.

PMID- 29581309
TI  - Cooption of an appendage-patterning gene cassette in the head segmentation of
      arachnids.
AB  - The jointed appendages of arthropods have facilitated the spectacular diversity
      and success of this phylum. Key to the regulation of appendage outgrowth is the
      Kruppel-like factor (KLF)/specificity protein (Sp) family of zinc finger
      transcription factors. In the fruit fly, Drosophila melanogaster, the Sp6-9
      homolog is activated by Wnt-1/wingless (wg) and establishes ventral appendage
      (leg) fate. Subsequently, Sp6-9 maintains expression of the axial patterning gene
      Distal-less (Dll), which promotes limb outgrowth. Intriguingly, in spiders, Dll
      has been reported to have a derived role as a segmentation gap gene, but the
      evolutionary origin and regulation of this function are not understood because
      functional investigations of the appendage-patterning regulatory network are
      restricted to insects. We tested the evolutionary conservation of the ancestral
      appendage-patterning network of arthropods with a functional approach in the
      spider. RNAi-mediated knockdown of the spider Sp6-9 ortholog resulted in
      diminution or loss of Dll expression and truncation of appendages, as well as
      loss of the two body segments specified by the early Dll function. In reciprocal
      experiments, Dll is shown not to be required for Sp6-9 expression. Knockdown of
      arrow (Wnt-1 coreceptor) disrupted segmentation and appendage development but did
      not affect the early Sp6-9 expression domain. Ectopic appendages generated in the
      spider "abdomen" by knockdown of the Hox gene Antennapedia-1 (Antp-1) expressed
      Sp6-9 comparably to wild-type walking legs. Our results support (i) the
      evolutionary conservation of an appendage-patterning regulatory network that
      includes canonical Wnt signaling, Sp6-9, and Dll and (ii) the cooption of the Sp6
      9/Dll regulatory cassette in arachnid head segmentation.

PMID- 29581311
TI  - Processes and patterns of interaction as units of selection: An introduction to
      ITSNTS thinking.
AB  - Many practicing biologists accept that nothing in their discipline makes sense
      except in the light of evolution, and that natural selection is evolution's
      principal sense-maker. But what natural selection actually is (a force or a
      statistical outcome, for example) and the levels of the biological hierarchy
      (genes, organisms, species, or even ecosystems) at which it operates directly are
      still actively disputed among philosophers and theoretical biologists. Most
      formulations of evolution by natural selection emphasize the differential
      reproduction of entities at one or the other of these levels. Some also recognize
      differential persistence, but in either case the focus is on lineages of material
      things: even species can be thought of as spatiotemporally restricted, if
      dispersed, physical beings. Few consider-as "units of selection" in their own
      right-the processes implemented by genes, cells, species, or communities. "It's
      the song not the singer" (ITSNTS) theory does that, also claiming that evolution
      by natural selection of processes is more easily understood and explained as
      differential persistence than as differential reproduction. ITSNTS was formulated
      as a response to the observation that the collective functions of microbial
      communities (the songs) are more stably conserved and ecologically relevant than
      are the taxa that implement them (the singers). It aims to serve as a useful
      corrective to claims that "holobionts" (microbes and their animal or plant hosts)
      are aggregate "units of selection," claims that often conflate meanings of that
      latter term. But ITSNS also seems broadly applicable, for example, to the
      evolution of global biogeochemical cycles and the definition of ecosystem
      function.

PMID- 29581310
TI  - Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1
      repression of the latent viral genome.
AB  - Adeno-associated virus (AAV) is a small human Dependovirus whose low
      immunogenicity and capacity for long-term persistence have led to its widespread
      use as vector for gene therapy. Despite great recent successes in AAV-based gene
      therapy, further improvements in vector technology may be hindered by an
      inadequate understanding of various aspects of basic AAV biology. AAV is unique
      in that its replication is largely dependent on a helper virus and cellular
      factors. In the absence of helper virus coinfection, wild-type AAV establishes
      latency through mechanisms that are not yet fully understood. Challenging the
      currently held model for AAV latency, we show here that the corepressor Kruppel
      associated box domain-associated protein 1 (KAP1) binds the latent AAV2 genome at
      the rep ORF, leading to trimethylation of AAV2-associated histone 3 lysine 9 and
      that the inactivation of KAP1 repression is necessary for AAV2 reactivation and
      replication. We identify a viral mechanism for the counteraction of KAP1 in which
      interference with the KAP1 phosphatase protein phosphatase 1 (PP1) by the AAV2
      Rep proteins mediates enhanced phosphorylation of KAP1-S824 and thus relief from
      KAP1 repression. Furthermore, we show that this phenomenon involves recruitment
      of the NIPP1 (nuclear inhibitor of PP1)-PP1alpha holoenzyme to KAP1 in a manner
      dependent upon the NIPP1 FHA domain, identifying NIPP1 as an interaction partner
      for KAP1 and shedding light on the mechanism through which PP1 regulates cellular
      KAP1 activity.

PMID- 29581313
TI  - Grassland biodiversity can pay.
AB  - The biodiversity-ecosystem functioning (BEF) literature provides strong evidence
      of the biophysical basis for the potential profitability of greater diversity but
      does not address questions of optimal management. BEF studies typically focus on
      the ecosystem outputs produced by randomly assembled communities that only differ
      in their biodiversity levels, measured by indices such as species richness.
      Landholders, however, do not randomly select species to plant; they choose
      particular species that collectively maximize profits. As such, their interest is
      not in comparing the average performance of randomly assembled communities at
      each level of biodiversity but rather comparing the best-performing communities
      at each diversity level. Assessing the best-performing mixture requires detailed
      accounting of species' identities and relative abundances. It also requires
      accounting for the financial cost of individual species' seeds, and the economic
      value of changes in the quality, quantity, and variability of the species'
      collective output-something that existing multifunctionality indices fail to do.
      This study presents an assessment approach that integrates the relevant factors
      into a single, coherent framework. It uses ecological production functions to
      inform an economic model consistent with the utility-maximizing decisions of a
      potentially risk-averse private landowner. We demonstrate the salience and
      applicability of the framework using data from an experimental grassland to
      estimate production relationships for hay and carbon storage. For that case, our
      results suggest that even a risk-neutral, profit-maximizing landowner would favor
      a highly diverse mix of species, with optimal species richness falling between
      the low levels currently found in commercial grasslands and the high levels found
      in natural grasslands.

PMID- 29581314
TI  - Total Laboratory Automation in Clinical Microbiology: a Micro-Comic Strip.

PMID- 29581315
TI  - Photo Quiz: A 9-Year-Old Girl with Eye Swelling and Drainage.

PMID- 29581316
TI  - Answer to April 2018 Photo Quiz.

PMID- 29581312
TI  - S-nitrosylation drives cell senescence and aging in mammals by controlling
      mitochondrial dynamics and mitophagy.
AB  - S-nitrosylation, a prototypic redox-based posttranslational modification, is
      frequently dysregulated in disease. S-nitrosoglutathione reductase (GSNOR)
      regulates protein S-nitrosylation by functioning as a protein denitrosylase.
      Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis
      broadly, including metabolic, cardiovascular, and immune function. Here, we
      demonstrate that GSNOR expression decreases in primary cells undergoing
      senescence, as well as in mice and humans during their life span. In stark
      contrast, exceptionally long-lived individuals maintain GSNOR levels. We also
      show that GSNOR deficiency promotes mitochondrial nitrosative stress, including
      excessive S-nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial
      dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity,
      suggest a molecular link between protein S-nitrosylation and mitochondria quality
      control in aging, and provide a redox-based perspective on aging with direct
      therapeutic implications.

PMID- 29581317
TI  - The Brief Case: Disseminated Neisseria gonorrhoeae in an 18-Year-Old Female.

PMID- 29581318
TI  - Closing the Brief Case: Disseminated Neisseria gonorrhoeae in an 18-Year-Old
      Female.

PMID- 29581319
TI  - The "3-Day Rule" for Stool Tests May Not Apply When Using PCR Panels.

PMID- 29581321
TI  - What's happening in Neurology(r).

PMID- 29581322
TI  - What's happening in Neurology(r)Clinical Practice.

PMID- 29581320
TI  - Reply to Beal et al., 'The "3-Day Rule" for Stool Tests May Not Apply When Using
      PCR Panels'.

PMID- 29581323
TI  - What's happening in Neurology(r)Genetics.

PMID- 29581324
TI  - What's happening in Neurology(r)Neuroimmunology & Neuroinflammation.

PMID- 29581325
TI  - Dilation lag in Horner syndrome can be measured with a diagnostic imaging system.

PMID- 29581326
TI  - Resident & Fellow Rounds.

PMID- 29581328
TI  - Editors' note: Sex-specific stroke incidence over time in the Greater
      Cincinnati/Northern Kentucky Stroke Study.

PMID- 29581327
TI  - Child Neurology: Type 1 sialidosis due to a novel mutation in NEU1 gene.

PMID- 29581329
TI  - Reader response: Sex-specific stroke incidence over time in the Greater
      Cincinnati/Northern Kentucky Stroke Study.

PMID- 29581330
TI  - Reader response: Sex-specific stroke incidence over time in the Greater
      Cincinnati/Northern Kentucky Stroke Study.

PMID- 29581331
TI  - Author response: Sex-specific stroke incidence over time in the Greater
      Cincinnati/Northern Kentucky Stroke Study.

PMID- 29581332
TI  - Editors' note: Expression of Concern: Does compensatory hyperparathyroidism
      predispose to ischemic stroke? Decreased bone mass and increased bone turnover
      with valproate therapy in adults with epilepsy; An alternative to vitamin D
      supplementation to prevent fractures in patients with MS; High prevalence of
      vitamin D deficiency and reduced bone mass in Parkinson's disease.

PMID- 29581334
TI  - Mystery Case: Tortuous hairs and tortuous blood vessels.

PMID- 29581333
TI  - Reader response: Expression of Concern: Does compensatory hyperparathyroidism
      predispose to ischemic stroke? Decreased bone mass and increased bone turnover
      with valproate therapy in adults with epilepsy; An alternative to vitamin D
      supplementation to prevent fractures in patients with MS; High prevalence of
      vitamin D deficiency and reduced bone mass in Parkinson's disease.

PMID- 29581335
TI  - Teaching NeuroImages: Sulcal artery syndrome: A hemicord infarct presenting with
      incomplete Brown-Sequard syndrome.

PMID- 29581336
TI  - Teaching Video NeuroImages: Vagoglossopharyngeal neuralgia mimicking a seizure.

PMID- 29581337
TI  - Epilepsy, antiepilepsy drugs, and serious car crashes.

PMID- 29581338
TI  - Failed Thrombectomy in Acute Ischemic Stroke: Return of the Stent?

PMID- 29581339
TI  - Stroke: Highlights of Selected Articles.

PMID- 29581340
TI  - Arterial Wall Imaging in Pediatric Stroke.
AB  - BACKGROUND AND PURPOSE: Arteriopathy is common in childhood arterial ischemic
      stroke (AIS) and predicts stroke recurrence. Currently available vascular imaging
      techniques mainly image the arterial lumen rather than the vessel wall and have a
      limited ability to differentiate among common arteriopathies. We aimed to
      investigate the value of a magnetic resonance imaging-based technique, namely
      noninvasive arterial wall imaging (AWI), for distinguishing among arteriopathy
      subtypes in a consecutive cohort of children presenting with AIS. METHODS:
      Children with confirmed AIS and magnetic resonance angiography underwent 3-Tesla
      AWI including T1-weighted 2-dimensional fluid-attenuated inversion recovery fast
      spin echo sequences pre- and post-gadolinium contrast. AWI characteristics,
      including wall enhancement, wall thickening, and luminal stenosis, were
      documented for all. RESULTS: Twenty-six children with AIS had AWI. Of these, 9
      (35%) had AWI enhancement. AWI enhancement was associated with anterior
      circulation magnetic resonance angiography abnormality and cortical infarction in
      8 of 9 (89%) children and normal magnetic resonance angiography with posterior
      circulation subcortical infarction in 1 (1 of 9; 11%) child. AWI enhancement was
      not seen in 17 (65%), 10 (59%) of whom had an abnormal magnetic resonance
      angiography. Distinct patterns of pre- and postcontrast signal abnormality were
      demonstrated in the vessel wall in the region of interest in children with
      transient cerebral arteriopathy, arterial dissection, primary central nervous
      system angiitis, dissecting aneurysm, and cardioembolic stroke. CONCLUSIONS: AWI
      is a noninvasive, high-resolution magnetic resonance AWI technique, which can be
      successfully used in children presenting with AIS. Patterns of AWI enhancement
      are recognizable and associated with specific AIS pathogeneses. Further studies
      are required to assess the additional diagnostic utility of AWI over routine
      vascular imaging techniques, in childhood AIS.

PMID- 29581341
TI  - Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke.
AB  - BACKGROUND AND PURPOSE: This study aims to describe the relationship between
      computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and
      radiological outcomes, in a cohort of patients who achieve successful reperfusion
      for acute ischemic stroke. METHODS: We included data from the CRISP (Computed
      Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which
      all patients underwent a baseline CTP scan before endovascular therapy. Patients
      were included if they had a mismatch on their baseline CTP scan and achieved
      successful endovascular reperfusion. Patients with mismatch were categorized into
      target mismatch and malignant mismatch profiles, according to the volume of their
      Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL).
      We investigated the impact of CTP-to-reperfusion times on probability of
      achieving functional independence (modified Rankin Scale, 0-2) at day 90 and
      radiographic outcomes at day 5. RESULTS: Of 156 included patients, 108 (59%) had
      the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In
      patients with the target mismatch profile, CTP-to-reperfusion time showed no
      association with functional independence (P=0.84), whereas in patients with
      malignant mismatch profile, CTP-to-reperfusion time was strongly associated with
      lower probability of functional independence (odds ratio, 0.08; P=0.003).
      Compared with patients with target mismatch, those with the malignant mismatch
      profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL;
      P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL;
      P=0.001). CONCLUSIONS: Compared with target mismatch patients, those with the
      malignant profile experience faster infarct growth and a steeper decline in the
      odds of functional independence, with longer delays between baseline imaging and
      reperfusion. However, this does not exclude the possibility of treatment benefit
      in patients with a malignant profile.

PMID- 29581342
TI  - Rescue Stenting for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A
      Multicenter Experience.
AB  - BACKGROUND AND PURPOSE: Effective rescue treatment has not yet been suggested in
      patients with mechanical thrombectomy (MT) failure. This study aimed to test
      whether rescue stenting (RS) improved clinical outcomes in MT-failed patients.
      METHODS: This is a retrospective analysis of the cohorts of the 16 comprehensive
      stroke centers between September 2010 and December 2015. We identified the
      patients who underwent MT but failed to recanalize intracranial internal carotid
      artery or middle cerebral artery M1 occlusion. Patients were dichotomized into 2
      groups: patients with RS and without RS after MT failure. Clinical and laboratory
      findings and outcomes were compared between the 2 groups. It was tested whether
      RS is associated with functional outcome. RESULTS: MT failed in 148 (25.0%) of
      the 591 patients with internal carotid artery or middle cerebral artery M1
      occlusion. Of these 148 patients, 48 received RS (RS group) and 100 were left
      without further treatment (no stenting group). Recanalization was successful in
      64.6% (31 of 48 patients) of RS group. Compared with no stenting group, RS group
      showed a significantly higher rate of good outcome (modified Rankin Scale score,
      0-2; 39.6% versus 22.0%; P=0.031) without increasing symptomatic intracranial
      hemorrhage (16.7% versus 20.0%; P=0.823) or mortality (12.5% versus 19.0%;
      P=0.360). Of the RS group, patients who had recanalization success had 54.8% of
      good outcome, which is comparable to that (55.4%) of recanalization success group
      with MT. RS remained independently associated with good outcome after adjustment
      of other factors (odds ratio, 3.393; 95% confidence interval, 1.192-9.655;
      P=0.022). Follow-up vascular imaging was available in the 23 (74.2%) of 31
      patients with recanalization success with RS. The stent was patent in 20 (87.0%)
      of the 23 patients. Glycoprotein IIb/IIIa inhibitor was significantly associated
      with stent patency but not with symptomatic intracranial hemorrhage. CONCLUSIONS:
      RS was independently associated with good outcomes without increasing symptomatic
      intracranial hemorrhage or mortality. RS seemed considered in MT-failed internal
      carotid artery or middle cerebral artery M1 occlusion.

PMID- 29581343
TI  - Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for
      Geographic and Racial Differences in Stroke).
AB  - BACKGROUND AND PURPOSE: Poststroke cognitive decline causes disability. Risk
      factors for poststroke cognitive decline independent of survivors' prestroke
      cognitive trajectories are uncertain. METHODS: Among 22 875 participants aged
      >=45 years without baseline cognitive impairment from the REGARDS cohort (Reasons
      for Geographic and Racial Differences in Stroke), enrolled from 2003 to 2007 and
      followed through September 2015, we measured the effect of incident stroke
      (n=694) on changes in cognitive functions and cognitive impairment (Six-Item
      Screener score <5) and tested whether patient factors modified the effect. Median
      follow-up was 8.2 years. RESULTS: Incident stroke was associated with acute
      declines in global cognition, new learning, verbal memory, and executive
      function. Acute declines in global cognition after stroke were greater in
      survivors who were black (P=0.04), men (P=0.04), and had cardioembolic (P=0.001)
      or large artery stroke (P=0.001). Acute declines in executive function after
      stroke were greater in survivors who had <high school education versus college
      graduates (P=0.01). Incident stroke was associated with faster declines in global
      cognition and executive function but not new learning or verbal memory compared
      with prestroke slopes. Faster declines in global cognition over years after
      stroke were greater in survivors who were older (P<0.01), resided outside the
      Stroke Belt (P=0.005), or had cardioembolic stroke (P=0.01). Faster declines in
      executive function over years after stroke were greater in survivors who were
      older (P<0.01) or lacked hypertension (P=0.03). CONCLUSIONS: Incident stroke
      alters a patient's cognitive trajectory, and this effect is greater with
      increasing age and cardioembolic stroke. Race, sex, geography, and hypertension
      status may modify the risk of poststroke cognitive decline.

PMID- 29581344
TI  - Eligibility for Endovascular Trial Enrollment in the 6- to 24-Hour Time Window:
      Analysis of a Single Comprehensive Stroke Center.
AB  - BACKGROUND AND PURPOSE: The results of the DAWN trial (Diffusion-Weighted Imaging
      or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the
      Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With
      Trevo) support the benefit of endovascular therapy in patients presenting beyond
      the 6-hour time window with anterior circulation large vessel occlusions. The
      impact of these results with respect to additional number of eligible patients in
      clinical practice remains unknown. METHODS: A retrospective review of ischemic
      stroke admissions to a single DAWN trial-participating comprehensive stroke
      center was performed during the DAWN enrollment period (November 2014 to February
      2017) to identify patients meeting criteria for DAWN and DEFUSE-3 (Endovascular
      Therapy Following Imaging Evaluation for Ischemic Stroke-3) eligibility. Patients
      presenting beyond 6 hours were further investigated to clarify reasons for trial
      exclusion. RESULTS: Of the 2667 patients with acute ischemic stroke admitted
      within the study period, 30% (n=792) presented within the 6- to 24-hour time
      window, and 47% (n=1242) had a National Institutes of Health Stroke Scale >=6.
      Further clinical trial-specific selection criteria were applied based on the
      presence of large vessel occlusion, baseline modified Rankin Scale score, core
      infarct, and perfusion imaging (when available). There were 45 patients who met
      all DAWN trial criteria and 47 to 58 patients who would meet DEFUSE-3 trial
      criteria. Thirty-three percent of DAWN-eligible patients are DEFUSE-3 ineligible.
      CONCLUSIONS: Of all patients with acute ischemic stroke presenting to a single
      comprehensive stroke center, 1.7% of patients qualified for DAWN clinical trial
      enrollment with an additional 0.6% to 1% qualifying for the DEFUSE-3 trial. These
      data predict an increase in thrombectomy utilization with important implications
      for comprehensive stroke center resource optimization and stroke systems of care.

PMID- 29581345
TI  - Ischemic Stroke Alters the Expression of the Transcribed Ultraconserved Regions
      of the Genome in Rat Brain.
AB  - BACKGROUND AND PURPOSE: Human and rodent genomes diverged ~75 million years ago.
      However, 481 regions of their genomes (200-779 nucleotide each) remained
      absolutely conserved and form noncoding RNAs known as transcribed ultraconserved
      regions (T-UCRs). The functional significance of T-UCRs is not apparent, but
      their altered expression is associated with many diseases, and thus thought to be
      critical for life. We presently investigated the poststroke temporal changes in
      the expression of T-UCRs with potential functional significance. METHODS: Male,
      spontaneously hypertensive rats were subjected to transient middle cerebral
      artery occlusion. Expression profile of T-UCRs was determined at 3, 6, and 12
      hours of reperfusion using microarrays and real-time polymerase chain reaction in
      the peri-infarct cortex. The putative functional significance of stroke
      responsive T-UCRs was identified by bioinformatics. RESULTS: Ischemia altered
      expression of 69 T-UCRs at >=1 time points of reperfusion compared with sham.
      Poststroke expression of the intragenic T-UCRs is independent of the expression
      of their parent gene mRNAs. Bioinformatics showed that the upstream/downstream
      and the parent genes of the T-UCRs modulate several biological and molecular
      functions, including metabolism, response to stimuli, cell communication, protein
      and nucleic acid binding. CONCLUSIONS: This first report shows that ischemic
      stroke temporally alters the noncoding ultraconserved RNAs in spontaneously
      hypertensive rats, but their functional significance is yet to be evaluated.

PMID- 29581347
TI  - Oral Contraceptives and Ischemic Stroke Risk.

PMID- 29581346
TI  - Accelerating Cell Therapy for Stroke in Japan: Regulatory Framework and
      Guidelines on Development of Cell-Based Products.

PMID- 29581348
TI  - Letter by Guijarro Regarding Article, "Cerebrovascular Outcomes With Proton Pump
      Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis".

PMID- 29581349
TI  - Letter by Zheng et al Regarding Article, "Cerebrovascular Outcomes With Proton
      Pump Inhibitors and Thienopyridines: A Systematic Review and Meta-Analysis".

PMID- 29581350
TI  - Response by Malhotra et al to the Letters Regarding Article, "Cerebrovascular
      Outcomes With Proton Pump Inhibitors and Thienopyridines: A Systematic Review and
      Meta-Analysis".

PMID- 29581351
TI  - Correction to: Effects of Prehospital Thrombolysis in Stroke Patients With
      Prestroke Dependency.

PMID- 29581352
TI  - Surgical adhesives in ophthalmology: history and current trends.
AB  - Tissue adhesives are gaining popularity in ophthalmology, as they could
      potentially reduce the complications associated with current surgical methods. An
      ideal tissue adhesive should have superior tensile strength, be non-toxic and
      anti-inflammatory, improve efficiency and be cost-effective. Both synthetic and
      biological glues are available. The primary synthetic glues include cyanoacrylate
      and the recently introduced polyethylene glycol (PEG) derivatives, while most
      biological glues are composed of fibrin. Cyanoacrylate has a high tensile
      strength, but rapidly polymerises upon contact with any fluid and has been
      associated with histotoxicity. Fibrin induces less toxic and inflammatory
      reactions, and its polymerisation time can be controlled. Tensile strength
      studies have shown that fibrin is not as strong as cyanoacrylate. While more
      research is needed, PEG variants currently appear to have the most promise. These
      glues are non-toxic, strong and time-effective. Through MEDLINE and internet
      searches, this paper presents a systematic review of the current applications of
      surgical adhesives to corneal, glaucoma, retinal, cataract and strabismus
      surgeries. Our review suggests that surgical adhesives have promise to reduce
      problems in current ophthalmic surgical procedures.

PMID- 29581353
TI  - Optical coherence tomography angiography in comparison with other multimodal
      imaging techniques in punctate inner choroidopathy.
AB  - AIMS: To characterise punctate lesions and choroidal neovascularisation (CNV) in
      eyes with punctate inner choroidopathy (PIC) using current standard multimodal
      imaging techniques and optical coherence tomography angiography (OCTA). METHODS:
      In our prospective, single-centre study, 20 individuals with PIC underwent
      imaging with spectral-domain optical coherence tomography (SD-OCT), fluorescein
      angiography (FA), indocyanine green angiography, fundus autofluorescence, fundus
      colour photography and OCTA. RESULTS: Thirty-two eyes of 20 patients were
      affected. Eight (20%) eyes revealed typical punctate lesions, while 24 (60%) eyes
      had confirmed CNV on SD-OCT and FA in addition to punctate lesions. Of these 24
      eyes with CNV, a reoccurrence of active CNV was detected in 5 (21%) eyes, a
      residual fluid in 3 (13%) eyes, while 16 (67%) eyes were defined as being stable.
      On OCTA, CNV was classified as having 'lacy wheel', 'pruned large-trunk' and
      'dead tree aspect' vessel shapes with or without areas of non-perfusion. The
      disease activity was dependent on several predictors in the regression analysis
      such as intraretinal fluid (p=0.0014), CNV type (p=0.0199), leakage (p<0.0001)
      and hypoperfusion/non-perfusion (p<0.0001) on OCTA. CONCLUSION: OCTA offers
      additional valuable insight into the current standard multimodal imaging
      techniques used for characterisation of PIC. This imaging technique can be a
      useful tool for analysis of disease activity.

PMID- 29581354
TI  - Memory Follicular Helper Invariant NKT Cells Recognize Lipid Antigens on Memory B
      Cells and Elicit Antibody Recall Responses.
AB  - Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or
      noncognate manner; however, whether cognate iNKT cell help induces B cell memory
      responses remains controversial, and the underlying mechanisms are still unclear.
      In this study, we demonstrated that, in the absence of follicular helper T cells,
      cognate iNKT cell help could promote B cell memory responses in mice that were
      dependent on the formation of memory follicular helper iNKT (iNKTFH) cells and
      their interactions with memory B cells in recall responses. Generation of memory
      iNKTFH cells required lipid Ag presentation by dendritic cells but not by B
      cells. Upon rechallenge, memory iNKTFH cells recognized lipid Ags presented by
      memory B cells, which recalled iNKTFH effector cells and elicited B cell memory
      responses. However, LPS, which promoted the synthesis of self-lipids, failed to
      elicit recall responses in the absence of exogenous lipid Ags.

PMID- 29581355
TI  - Filamin A Is Required for Optimal T Cell Integrin-Mediated Force Transmission,
      Flow Adhesion, and T Cell Trafficking.
AB  - T cells traffic from the bloodstream into tissues to perform their functions in
      the immune system and are therefore subjected to a range of different mechanical
      forces. Integrins are essential for T cell trafficking into the tissues, as they
      mediate firm adhesion between the T cell and the endothelium under shear flow
      conditions. In addition, integrins are important for the formation of the contact
      between the T cell and the APC required for T cell activation. The actin-binding
      protein filamin A (FlnA) provides an important link between the integrin and the
      actin cytoskeleton. FlnA has been reported to function as an integrin inhibitor
      by competing with talin. However, its role in regulating integrin-dependent
      immune functions in vivo is currently poorly understood. In this study, we have
      investigated the role of FlnA in T cells, using T cell-specific FlnA knockout
      mice. We report that FlnA is required for the formation of strong integrin-ligand
      bonds under shear flow and for the generation of integrin-mediated T cell
      traction forces on ligand-coated hydrogels. Consequently, absence of FlnA leads
      to a reduction in T cell adhesion to integrin ligands under conditions of shear
      flow, as well as reduced T cell trafficking into lymph nodes and sites of skin
      inflammation. In addition, FlnA is not needed for T cell activation in vivo,
      which occurs in shear-free conditions in lymphoid organs. Our results therefore
      reveal a role of FlnA in integrin force transmission and T cell trafficking in
      vivo.

PMID- 29581356
TI  - ICOS Signaling Controls Induction and Maintenance of Collagen-Induced Arthritis.
AB  - ICOS is a key costimulatory receptor facilitating differentiation and function of
      follicular helper T cells and inflammatory T cells. Rheumatoid arthritis patients
      were shown to have elevated levels of ICOS+ T cells in the synovial fluid,
      suggesting a potential role of ICOS-mediated T cell costimulation in autoimmune
      joint inflammation. In this study, using ICOS knockout and knockin mouse models,
      we found that ICOS signaling is required for the induction and maintenance of
      collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis. For the
      initiation of CIA, the Tyr181-based SH2-binding motif of ICOS that is known to
      activate PI3K was critical for Ab production and expansion of inflammatory T
      cells. Furthermore, we found that Tyr181-dependent ICOS signaling is important
      for maintenance of CIA in an Ab-independent manner. Importantly, we found that a
      small molecule inhibitor of glycolysis, 3-bromopyruvate, ameliorates established
      CIA, suggesting an overlap between ICOS signaling, PI3K signaling, and glucose
      metabolism. Thus, we identified ICOS as a key costimulatory pathway that controls
      induction and maintenance of CIA and provide evidence that T cell glycolytic
      pathways can be potential therapeutic targets for rheumatoid arthritis.

PMID- 29581357
TI  - Cutting Edge: Imbalanced Cation Homeostasis in MAGT1-Deficient B Cells
      Dysregulates B Cell Development and Signaling in Mice.
AB  - Cation homeostasis, in relation to various immune-suppressive diseases, is a
      novel field of investigation. Recently, patients with a loss-of-function mutation
      in magnesium transporter 1 (MAGT1) were reported to present a dysregulated Mg2+
      homeostasis in T lymphocytes. Using Magt1-knockout mice (Magt1-/y ), we show that
      Mg2+ homeostasis was impaired in Magt1-/y B cells and Ca2+ influx was increased
      after BCR stimulation, whereas T and NK cell function was unaffected.
      Consequently, mutant B cells displayed an increased phosphorylation of BCR
      related proteins differentially affecting protein kinase C activation. These in
      vitro findings translated into increased frequencies of CD19+ B cells and
      marginal zone B cells and decreased frequencies of plasma cells among CD45+
      splenocytes in vivo. Altogether, our study demonstrates for the first time, to
      our knowledge, that abolished MAGT1 function causes imbalanced cation homeostasis
      and developmental responses in B cells. Therefore, this study might contribute to
      a further understanding of B cell-related pathologies.

PMID- 29581358
TI  - Deregulated Mucosal Immune Surveillance through Gut-Associated Regulatory T Cells
      and PD-1+ T Cells in Human Colorectal Cancer.
AB  - Disturbed balance between immune surveillance and tolerance may lead to poor
      clinical outcomes in some malignancies. In paired analyses of adenocarcinoma and
      normal mucosa from 142 patients, we found a significant increase of the CD4/CD8
      ratio and accumulation of regulatory T cells (Tregs) within the adenocarcinoma.
      The increased frequency of Tregs correlated with the local infiltration and
      extension of the tumor. There was concurrent maturation arrest, upregulation of
      programmed death-1 expression, and functional impairment in CD8+ T cells (CTLs)
      isolated from the adenocarcinoma. Adenocarcinoma-associated Tregs directly
      inhibit the function of normal human CTLs in vitro. With histopathological
      analysis, Foxp3+ Tregs were preferentially located in stroma. Concurrent
      transcriptome analysis of epithelial cells, stromal cells, and T cell subsets
      obtained from carcinomatous and normal intestinal samples from patients revealed
      a distinct gene expression signature in colorectal adenocarcinoma-associated
      Tregs, with overexpression of CCR1, CCR8, and TNFRSF9, whereas their ligands CCL4
      and TNFSF9 were found upregulated in cancerous epithelium. Overexpression of WNT2
      and CADM1, associated with carcinogenesis and metastasis, in cancer-associated
      stromal cells suggests that both cancer cells and stromal cells play important
      roles in the development and progression of colorectal cancer through the
      formation of a tumor microenvironment. The identification of CTL anergy by Tregs
      and the unique gene expression signature of human Tregs and stromal cells in
      colorectal cancer patients may facilitate the development of new therapeutics
      against malignancies.

PMID- 29581359
TI  - Remembering Dr Ray Lipicky.

PMID- 29581360
TI  - Reflections on the Design of Clinical Trials: A Conversation With Raymond J.
      Lipicky, MD.

PMID- 29581361
TI  - CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel Percutaneous Coronary
      Intervention in Cardiogenic Shock): Implications on Guideline Recommendations.

PMID- 29581362
TI  - Innovations in Radiation Safety During Cardiovascular Catheterization.

PMID- 29581363
TI  - New Therapeutic Target in Heart Failure: Achieving and Maintaining Normokalemia.

PMID- 29581364
TI  - Adult Congenital Heart Disease and Radiation Exposure: The Malignant Price of
      Cardiac Care.

PMID- 29581365
TI  - Added Value of Cardiovascular Magnetic Resonance in Primary Mitral Regurgitation.

PMID- 29581367
TI  - Wide QRS Complex Tachycardia: What the Algorithms Fear.

PMID- 29581368
TI  - Pulmonary Artery Banding for Functional Regeneration of End-Stage Dilated
      Cardiomyopathy in Young Children: World Network Report.

PMID- 29581366
TI  - Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and
      Implications for Management.
AB  - The prevalence of obesity has increased globally over the last 2 decades.
      Although the body mass index has been a convenient and simple index of obesity at
      the population level, studies have shown that obesity defined by body mass index
      alone is a remarkably heterogeneous condition with varying cardiovascular and
      metabolic manifestations across individuals. Adipose tissue is an exquisitely
      active metabolic organ engaged in cross-talk between various systems;
      perturbation of adipose tissue results in a pathological response to positive
      caloric balance in susceptible individuals that directly and indirectly
      contributes to cardiovascular and metabolic disease. Inadequate subcutaneous
      adipose tissue expansion in the face of dietary triglycerides leads to visceral
      and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin
      resistance. Conversely, preferential fat storage in the lower body depot may act
      as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid
      overflow and ectopic fat. Translational, epidemiological, and clinical studies
      over the past 30 years have clearly demonstrated a strong link between visceral
      and ectopic fat and the development of a clinical syndrome characterized by
      atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension,
      atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship
      is even more nuanced when clinical entities such as metabolically healthy obesity
      phenotype and the obesity paradox are considered. Although it is clear that the
      accumulation of visceral/ectopic fat is a major contributor to cardiovascular and
      metabolic risk above and beyond the body mass index, implementation of fat
      distribution assessment into clinical practice remains a challenge.
      Anthropometric indexes of obesity are easily implemented, but newer imaging-based
      methods offer improved sensitivity and specificity for measuring specific depots.
      Lifestyle, pharmacological, and surgical interventions allow a multidisciplinary
      approach to overweight/obesity that may improve outcomes and align with a public
      health message to combat the growing epidemic of obesity worldwide and to build
      healthier lives free of cardiovascular diseases.

PMID- 29581369
TI  - Letter by Cerit Regarding Article, "Cerebral Perfusion and the Risk of Dementia:
      A Population-Based Study".

PMID- 29581370
TI  - Letter by Bailey et al Regarding Article, "Cerebral Perfusion and the Risk of
      Dementia: A Population-Based Study".

PMID- 29581371
TI  - Response by Wolters and Ikram to Letter Regarding Article, "Cerebral Perfusion
      and the Risk of Dementia: A Population-Based Study".

PMID- 29581372
TI  - Letter by Khan and Boyle Regarding Article, "Early Use of N-Acetylcysteine (NAC)
      With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary
      Intervention for ST-Segment Elevation Myocardial Infarction Reduces Myocardial
      Infarct Size (The NACIAM Trial [N-Acetylcysteine in Acute Myocardial
      Infarction])".

PMID- 29581373
TI  - Letter by Mansour et al Regarding Article, "Early Use of N-Acetylcysteine With
      Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention
      for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size
      (the NACIAM Trial [N-Acetylcysteine in Acute Myocardial Infarction])".

PMID- 29581374
TI  - Letter by Ye et al Regarding Article, "Early Use of N-Acetylcysteine With Nitrate
      Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST
      Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the
      NACIAM Trial [N-Acetylcysteine in Acute Myocardial Infarction])".

PMID- 29581375
TI  - Response by Pasupathy et al to Letters Regarding Article, "Early Use of N
      acetylcysteine (NAC) With Nitrate Therapy in Patients Undergoing Primary
      Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
      Reduces Myocardial Infarct Size (The NACIAM Trial [N-Acetylcysteine in Acute
      Myocardial Infarction])".

PMID- 29581376
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Survival and Left Ventricular
      Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis".

PMID- 29581377
TI  - Response by Ammirati et al to Letter Regarding Article, "Survival and Left
      Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis".

PMID- 29581378
TI  - HIPK2-Mediated Transcriptional Control of NMDA Receptor Subunit Expression
      Regulates Neuronal Survival and Cell Death.
AB  - NMDA receptors are critical for neuronal communication. Dysfunction in NMDA
      receptors has been implicated in neuropsychiatric diseases. While it is well
      recognized that the composition of NMDA receptors undergoes a GluN2B-to-GluN2A
      switch in early postnatal life, the mechanism regulating this switch remains
      unclear. Using transcriptomic and functional analyses in brain tissues from male
      and female Hipk2+/+ and Hipk2-/- mice, we showed that the HIPK2-JNK-c-Jun pathway
      is important in suppressing the transcription of Grin2a and Grin2c, which encodes
      the GluN2A and GluN2C subunits of the NMDA receptors, respectively. Loss of HIPK2
      leads to a significant decrease in JNK-c-Jun signaling, which in turn derepresses
      the transcription of Grin2a and Grin2c mRNA and upregulates GluN2A and GluN2C
      protein levels. These changes result in a significant increase of GluN2A/GluN2B
      ratio in synapse and mitochondria, a persistent activation of the ERK-CREB
      pathway and the upregulation of synaptic activity-regulated genes, which
      collectively contribute to the resistance of Hipk2-/- neurons to cell death
      induced by mitochondrial toxins.SIGNIFICANCE STATEMENT We identify HIPK2-JNK-c
      Jun signaling as a key mechanism that regulates the transcription of NMDA
      receptor subunits GluN2A and GluN2C in vivo Our results provide insights into a
      previously unrecognized molecular mechanism that control the switch of NMDA
      receptor subunits in early postnatal brain development. Furthermore, we provide
      evidence that changes in the ratio of NMDA subunits GluN2A/GluN2B can also be
      detected in the synapse and mitochondria, which contributes to a persistent
      activation of the prosurvival ERK-CREB pathway and its downstream target genes.
      Collectively, these changes protect HIPK2 deficient neurons from mitochondrial
      toxins.

PMID- 29581379
TI  - Visual Mismatch and Predictive Coding: A Computational Single-Trial ERP Study.
AB  - Predictive coding (PC) posits that the brain uses a generative model to infer the
      environmental causes of its sensory data and uses precision-weighted prediction
      errors (pwPEs) to continuously update this model. While supported by much
      circumstantial evidence, experimental tests grounded in formal trial-by-trial
      predictions are rare. One partial exception is event-related potential (ERP)
      studies of the auditory mismatch negativity (MMN), where computational models
      have found signatures of pwPEs and related model-updating processes. Here, we
      tested this hypothesis in the visual domain, examining possible links between
      visual mismatch responses and pwPEs. We used a novel visual "roving standard"
      paradigm to elicit mismatch responses in humans (of both sexes) by unexpected
      changes in either color or emotional expression of faces. Using a hierarchical
      Bayesian model, we simulated pwPE trajectories of a Bayes-optimal observer and
      used these to conduct a comprehensive trial-by-trial analysis across the time *
      sensor space. We found significant modulation of brain activity by both color and
      emotion pwPEs. The scalp distribution and timing of these single-trial pwPE
      responses were in agreement with visual mismatch responses obtained by
      traditional averaging and subtraction (deviant-minus-standard) approaches.
      Finally, we compared the Bayesian model to a more classical change model of MMN.
      Model comparison revealed that trial-wise pwPEs explained the observed mismatch
      responses better than categorical change detection. Our results suggest that
      visual mismatch responses reflect trial-wise pwPEs, as postulated by PC. These
      findings go beyond classical ERP analyses of visual mismatch and illustrate the
      utility of computational analyses for studying automatic perceptual
      processes.SIGNIFICANCE STATEMENT Human perception is thought to rely on a
      predictive model of the environment that is updated via precision-weighted
      prediction errors (pwPEs) when events violate expectations. This "predictive
      coding" view is supported by studies of the auditory mismatch negativity brain
      potential. However, it is less well known whether visual perception of mismatch
      relies on similar processes. Here we combined computational modeling and
      electroencephalography to test whether visual mismatch responses reflected trial
      by-trial pwPEs. Applying a Bayesian model to series of face stimuli that violated
      expectations about color or emotional expression, we found significant modulation
      of brain activity by both color and emotion pwPEs. A categorical change detection
      model performed less convincingly. Our findings support the predictive coding
      interpretation of visual mismatch responses.

PMID- 29581381
TI  - Amazon sugar cane: A threat to the forest.

PMID- 29581382
TI  - Margaret McCartney: Medicine must do better on gender.

PMID- 29581380
TI  - Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.
AB  - Healthy aging is associated with marked effects on sleep, including its daily
      amount and architecture, as well as the specific EEG oscillations. Neither the
      neurophysiological underpinnings nor the biological significance of these changes
      are understood, and crucially the question remains whether aging is associated
      with reduced sleep need or a diminished capacity to generate sufficient sleep.
      Here we tested the hypothesis that aging may affect local cortical networks,
      disrupting the capacity to generate and sustain sleep oscillations, and with it
      the local homeostatic response to sleep loss. We performed chronic recordings of
      cortical neural activity and local field potentials from the motor cortex in
      young and older male C57BL/6J mice, during spontaneous waking and sleep, as well
      as during sleep after sleep deprivation. In older animals, we observed an
      increase in the incidence of non-rapid eye movement sleep local field potential
      slow waves and their associated neuronal silent (OFF) periods, whereas the
      overall pattern of state-dependent cortical neuronal firing was generally similar
      between ages. Furthermore, we observed that the response to sleep deprivation at
      the level of local cortical network activity was not affected by aging. Our data
      thus suggest that the local cortical neural dynamics and local sleep homeostatic
      mechanisms, at least in the motor cortex, are not impaired during healthy
      senescence in mice. This indicates that powerful protective or compensatory
      mechanisms may exist to maintain neuronal function stable across the life span,
      counteracting global changes in sleep amount and architecture.SIGNIFICANCE
      STATEMENT The biological significance of age-dependent changes in sleep is
      unknown but may reflect either a diminished sleep need or a reduced capacity to
      generate deep sleep stages. As aging has been linked to profound disruptions in
      cortical sleep oscillations and because sleep need is reflected in specific
      patterns of cortical activity, we performed chronic electrophysiological
      recordings of cortical neural activity during waking, sleep, and after sleep
      deprivation from young and older mice. We found that all main hallmarks of
      cortical activity during spontaneous sleep and recovery sleep after sleep
      deprivation were largely intact in older mice, suggesting that the well-described
      age-related changes in global sleep are unlikely to arise from a disruption of
      local network dynamics within the neocortex.

PMID- 29581383
TI  - High altitude arterialised capillary earlobe blood gas measurement using the
      Abbott i-STAT.
AB  - INTRODUCTION: Measurement of physiological parameters in extreme environments is
      essential to advancing knowledge, prophylaxis and treatment of altitude sickness.
      Point-of-care testing facilitates investigation in non-specialist and remote
      settings, as well as becoming increasingly popular at the bedside for real-time
      results in the clinical environment. Arterialised capillary earlobe blood gases
      are recommended as a valid alternative to arterial sampling in research. This
      study aimed to test the feasibility of obtaining and analysing daily earlobe
      samples at high altitude. METHODS: From 17 to 24 January 2016, 24 participants on
      a research expedition to Ecuador underwent daily earlobe blood gas measurements
      including pH, partial pressure of oxygen and partial pressure of carbon dioxide
      to 5043 m. Samples were analysed using an Abbott i-STAT blood gas analyser and
      G3+ cartridges. RESULTS: Daily measurements were successfully obtained and
      analysed at the point of care in 23/24 participants and were well tolerated with
      no adverse events. 12% (27/220) cartridges failed and required repeat sampling.
      CONCLUSIONS: Daily earlobe blood gas analysis using the Abbott i-STAT is feasible
      in a protected environment at high altitude. Participants and equipment should be
      kept warm before and during testing. Spare cartridges should be available. This
      methodology may be useful for both research and therapeutic measurements in
      remote, rural and wilderness medicine.

PMID- 29581384
TI  - Ultrasound is more reliable than inflammatory parameters to evaluate disease
      activity in patients with RA receiving tocilizumab therapy.
AB  - The target of treatment for rheumatoid arthritis (RA) is to keep low disease
      activity or remission. Tocilizumab can fully inhibit interleukin-6 and C reactive
      protein (CRP) production. The goal of the study is to search whether tocilizumab
      treatment compared with adalimumab treatment had the similar effect on sonography
      and inflammatory parameters in patients with RA. We compared ultrasound scores
      and inflammatory parameters between patients with RA receiving tocilizumab
      therapy and those receiving adalimumab therapy. Power Doppler (PD) ultrasound and
      grayscale synovial hypertrophy on bilateral radiocarpal joints were performed.
      Inflammatory mediators and ultrasound scores were compared by independent t-test
      between the adalimumab and tocilizumab groups. 65 patients with RA (32
      tocilizumab and 33 adalimumab) were included. Between the two groups, there were
      no significant differences in age, gender, rheumatoid factors and anticyclic
      citrullinated peptide antibody. Following biological therapy, the ultrasound
      score was 2.33 in the tocilizumab group and 2.08 in the adalimumab group
      (p=0.570), while the erythrocyte sedimentation rate, CRP and Disease Activity
      Score in 28 joints (DAS28) were lower in the tocilizumab group. So ultrasound
      scores between the two groups were not significantly different, but the
      laboratory parameters and DAS28 were lower in the tocilizumab group than in the
      adalimumab group. Hence, to assess disease activity cannot be based only on
      clinical evaluations, so we suggest PD ultrasound to be used for all patients on
      tocilizumab therapy and reflect the true disease activity in these patients.

PMID- 29581386
TI  - Siglec expression on the surface of human, bull and ram sperm.
AB  - Sialic acid (Sia) is a major constituent of both the sperm glycocalyx and female
      reproductive mucosal surface and is involved in regulating sperm migration,
      uterotubal reservoir formation and oocyte binding. Siglecs (sialic acid-binding
      immunoglobulin - like lectins) commonly found on immune cells, bind to Sia in a
      linkage- and sugar-specific manner and often mediate cell-to-cell interactions
      and signalling. Proteomic and transcriptomic analysis of human and bovine sperm
      have listed Siglecs, but to date, their presence and/or localisation on sperm has
      not been studied. Therefore, the aim of this study was to characterise the
      presence of Siglecs on the surface of bovine, human and ovine sperm using both
      immunostaining and Western blotting. Siglec 1, 2, 5, 6, 10 and 14 were identified
      and displayed both species- and regional-specific expression on sperm. Almost
      universal expression across Siglecs and species was evident in the sperm neck and
      midpiece region while variable expression among Siglecs, similar among species,
      was detected in the head and tail regions of the sperm. The possible role for
      these proteins on sperm is discussed.

PMID- 29581385
TI  - Advanced body composition assessment: from body mass index to body composition
      profiling.
AB  - This paper gives a brief overview of common non-invasive techniques for body
      composition analysis and a more in-depth review of a body composition assessment
      method based on fat-referenced quantitative MRI. Earlier published studies of
      this method are summarized, and a previously unpublished validation study, based
      on 4753 subjects from the UK Biobank imaging cohort, comparing the quantitative
      MRI method with dual-energy X-ray absorptiometry (DXA) is presented. For whole
      body measurements of adipose tissue (AT) or fat and lean tissue (LT), DXA and
      quantitative MRIs show excellent agreement with linear correlation of 0.99 and
      0.97, and coefficient of variation (CV) of 4.5 and 4.6 per cent for fat (computed
      from AT) and LT, respectively, but the agreement was found significantly lower
      for visceral adipose tissue, with a CV of >20 per cent. The additional ability of
      MRI to also measure muscle volumes, muscle AT infiltration and ectopic fat, in
      combination with rapid scanning protocols and efficient image analysis tools,
      makes quantitative MRI a powerful tool for advanced body composition assessment.

PMID- 29581387
TI  - RNASET2 impairs the sperm motility via PKA/PI3K/calcium signal pathways.
AB  - Asthenozoospermia is one of the leading causes of male infertility owing to a
      decline in sperm motility. Herein, we determined if there is a correlation
      between RNASET2 content on human spermatozoa and sperm motility in 205 semen
      samples from both asthenozoospermia patients and normozoospermia individuals.
      RNASET2 content was higher in sperm from asthenozoospermia patients than in
      normozoospermia individuals. On the other hand, its content was inversely
      correlated with sperm motility as well as progressive motility. Moreover, the
      inhibitory effect of RNASET2 on sperm motility was induced by incubating
      normozoospermic sperm with RNase T2 protein. Such treatment caused significant
      declines in intracellular spermatozoa PKA activity, PI3K activity and calcium
      level, which resulted in severely impaired sperm motility, and the sperm motility
      was largely rescued by cAMP supplementation. Finally, protein immunoprecipitation
      and mass spectrometry identified proteins whose interactions with RNASET2 were
      associated with declines in human spermatozoa motility. AKAP4, a protein
      regulating PKA activity, coimmunoprecipated with RNASET2 and they colocalized
      with one another in the sperm tail, which might contribute to reduced sperm
      motility. Thus, RNASET2 may be a novel biomarker of asthenozoospermia. Increases
      in RNASET2 can interact with AKAP4 in human sperm tail and subsequently reduce
      sperm motility by suppressing PKA/PI3K/calcium signaling pathways.

PMID- 29581388
TI  - Maternal inheritance of mitochondria: implications for male fertility?
AB  - Evolutionary theory predicts maternal inheritance of the mitochondria will lead
      to the accumulation of mutations in the mitochondrial DNA (mtDNA) that impair
      male fertility, but leave females unaffected. The hypothesis has been referred to
      as 'Mother's Curse'. There are many examples of mtDNA mutations or haplotypes, in
      humans and other metazoans, associated with decreases in sperm performance, but
      seemingly few reports of associations involving female reproductive traits; an
      observation that has been used to support the Mother's Curse hypothesis. However,
      it is unclear whether apparent signatures of male bias in mitochondrial genetic
      effects on fertility reflect an underlying biological bias or a technical bias
      resulting from a lack of studies to have screened for female effects. Here, we
      conduct a systematic literature search of studies reporting mitochondrial genetic
      effects on fertility-related traits in gonochoristic metazoans (animals with two
      distinct sexes). Studies of female reproductive outcomes were sparse, reflecting
      a large technical sex bias across the literature. We were only able to make a
      valid assessment of sex specificity of mitochondrial genetic effects in 30% of
      cases. However, in most of these cases, the effects were male biased, including
      examples of male bias associated with mtDNA mutations in humans. These results
      are therefore consistent with the hypothesis that maternal inheritance has
      enriched mtDNA sequences with mutations that specifically impair male fertility.
      However, future research that redresses the technical imbalance in studies
      conducted per sex will be key to enabling researchers to fully assess the wider
      implications of the Mother's Curse hypothesis to male reproductive biology.

PMID- 29581389
TI  - Collective movement in ecology: from emerging technologies to conservation and
      management.
AB  - Recent advances in technology and quantitative methods have led to the emergence
      of a new field of study that stands to link insights of researchers from two
      closely related, but often disconnected disciplines: movement ecology and
      collective animal behaviour. To date, the field of movement ecology has focused
      on elucidating the internal and external drivers of animal movement and the
      influence of movement on broader ecological processes. Typically, tracking and/or
      remote sensing technology is employed to study individual animals in natural
      conditions. By contrast, the field of collective behaviour has quantified the
      significant role social interactions play in the decision-making of animals
      within groups and, to date, has predominantly relied on controlled laboratory
      based studies and theoretical models owing to the constraints of studying
      interacting animals in the field. This themed issue is intended to formalize the
      burgeoning field of collective movement ecology which integrates research from
      both movement ecology and collective behaviour. In this introductory paper, we
      set the stage for the issue by briefly examining the approaches and current
      status of research in these areas. Next, we outline the structure of the theme
      issue and describe the obstacles collective movement researchers face, from data
      acquisition in the field to analysis and problems of scale, and highlight the key
      contributions of the assembled papers. We finish by presenting research that
      links individual and broad-scale ecological and evolutionary processes to
      collective movement, and finally relate these concepts to emerging challenges for
      the management and conservation of animals on the move in a world that is
      increasingly impacted by human activity.This article is part of the theme issue
      'Collective movement ecology'.

PMID- 29581390
TI  - Challenges and solutions for studying collective animal behaviour in the wild.
AB  - Mobile animal groups provide some of the most compelling examples of self
      organization in the natural world. While field observations of songbird flocks
      wheeling in the sky or anchovy schools fleeing from predators have inspired
      considerable interest in the mechanics of collective motion, the challenge of
      simultaneously monitoring multiple animals in the field has historically limited
      our capacity to study collective behaviour of wild animal groups with precision.
      However, recent technological advancements now present exciting opportunities to
      overcome many of these limitations. Here we review existing methods used to
      collect data on the movements and interactions of multiple animals in a natural
      setting. We then survey emerging technologies that are poised to revolutionize
      the study of collective animal behaviour by extending the spatial and temporal
      scales of inquiry, increasing data volume and quality, and expediting the post
      processing of raw data.This article is part of the theme issue 'Collective
      movement ecology'.

PMID- 29581391
TI  - Inferring influence and leadership in moving animal groups.
AB  - Collective decision-making is a daily occurrence in the lives of many group
      living animals, and can have critical consequences for the fitness of
      individuals. Understanding how decisions are reached, including who has influence
      and the mechanisms by which information and preferences are integrated, has posed
      a fundamental challenge. Here, we provide a methodological framework for studying
      influence and leadership in groups. We propose that individuals have influence if
      their actions result in some behavioural change among their group-mates, and are
      leaders if they consistently influence others. We highlight three components of
      influence (influence instances, total influence and consistency of influence),
      which can be assessed at two levels (individual-to-individual and individual-to
      group). We then review different methods, ranging from individual positioning
      within groups to information-theoretic approaches, by which influence has been
      operationally defined in empirical studies, as well as how such observations can
      be aggregated to give insight into the underlying decision-making process. We
      focus on the domain of collective movement, with a particular emphasis on methods
      that have recently been, or are being, developed to take advantage of
      simultaneous tracking data. We aim to provide a resource bringing together
      methodological tools currently available for studying leadership in moving animal
      groups, as well as to discuss the limitations of current methodologies and
      suggest productive avenues for future research.This article is part of the theme
      issue 'Collective movement ecology'.

PMID- 29581392
TI  - Disentangling social interactions and environmental drivers in multi-individual
      wildlife tracking data.
AB  - While many animal species exhibit strong conspecific interactions, movement
      analyses of wildlife tracking datasets still largely focus on single individuals.
      Multi-individual wildlife tracking studies provide new opportunities to explore
      how individuals move relative to one another, but such datasets are frequently
      too sparse for the detailed, acceleration-based analytical methods typically
      employed in collective motion studies. Here, we address the methodological gap
      between wildlife tracking data and collective motion by developing a general
      method for quantifying movement correlation from sparsely sampled data. Unlike
      most existing techniques for studying the non-independence of individual
      movements with wildlife tracking data, our approach is derived from an
      analytically tractable stochastic model of correlated movement. Our approach
      partitions correlation into a deterministic tendency to move in the same
      direction termed 'drift correlation' and a stochastic component called 'diffusive
      correlation'. These components suggest the mechanisms that coordinate movements,
      with drift correlation indicating external influences, and diffusive correlation
      pointing to social interactions. We use two case studies to highlight the ability
      of our approach both to quantify correlated movements in tracking data and to
      suggest the mechanisms that generate the correlation. First, we use an abrupt
      change in movement correlation to pinpoint the onset of spring migration in
      barren-ground caribou. Second, we show how spatial proximity mediates
      intermittently correlated movements among khulans in the Gobi desert. We conclude
      by discussing the linkages of our approach to the theory of collective
      motion.This article is part of the theme issue 'Collective movement ecology'.

PMID- 29581393
TI  - The importance of individual variation in the dynamics of animal collective
      movements.
AB  - Animal collective movements are a key example of a system that links two clearly
      defined levels of organization: the individual and the group. Most models
      investigating collective movements have generated coherent collective behaviours
      without the inclusion of individual variability. However, new individual-based
      models, together with emerging empirical information, emphasize that within-group
      heterogeneity may strongly influence collective movement behaviour. Here we (i)
      review the empirical evidence for individual variation in animal collective
      movements, (ii) explore how theoretical investigations have represented
      individual heterogeneity when modelling collective movements and (iii) present a
      model to show how within-group heterogeneity influences the collective properties
      of a group. Our review underscores the need to consider variability at the level
      of the individual to improve our understanding of how individual decision rules
      lead to emergent movement patterns, and also to yield better quantitative
      predictions of collective behaviour.This article is part of the theme issue
      'Collective movement ecology'.

PMID- 29581395
TI  - Different bees, different needs: how nest-site requirements have shaped the
      decision-making processes in homeless honeybees (Apis spp.).
AB  - During reproductive swarming, a honeybee swarm needs to decide on a new nest site
      and then move to the chosen site collectively. Most studies of swarming and nest
      site selection are based on one species, Apis mellifera Natural colonies of A.
      mellifera live in tree cavities. The quality of the cavity is critical to the
      survival of a swarm. Other honeybee species nest in the open, and have less
      strict nest-site requirements, such as the open-nesting dwarf honeybee Apis
      floreaApis florea builds a nest comprised of a single comb suspended from a twig.
      For a cavity-nesting species, there is only a limited number of potential nest
      sites that can be located by a swarm, because suitable sites are scarce. By
      contrast, for an open-nesting species, there is an abundance of equally suitable
      twigs. While the decision-making process of cavity-nesting bees is geared towards
      selecting the best site possible, open-nesting species need to coordinate
      collective movement towards areas with potential nest sites. Here, we argue that
      the nest-site selection processes of A. florea and A. mellifera have been shaped
      by each species' specific nest-site requirements. Both species use the same
      behavioural algorithm, tuned to allow each species to solve their species
      specific problem.This article is part of the theme issue 'Collective movement
      ecology'.

PMID- 29581394
TI  - Collective animal navigation and migratory culture: from theoretical models to
      empirical evidence.
AB  - Animals often travel in groups, and their navigational decisions can be
      influenced by social interactions. Both theory and empirical observations suggest
      that such collective navigation can result in individuals improving their ability
      to find their way and could be one of the key benefits of sociality for these
      species. Here, we provide an overview of the potential mechanisms underlying
      collective navigation, review the known, and supposed, empirical evidence for
      such behaviour and highlight interesting directions for future research. We
      further explore how both social and collective learning during group navigation
      could lead to the accumulation of knowledge at the population level, resulting in
      the emergence of migratory culture.This article is part of the theme issue
      'Collective movement ecology'.

PMID- 29581396
TI  - Synchronization, coordination and collective sensing during thermalling flight of
      freely migrating white storks.
AB  - Exploring how flocks of soaring migrants manage to achieve and maintain
      coordination while exploiting thermal updrafts is important for understanding how
      collective movements can enhance the sensing of the surrounding environment. Here
      we examined the structural organization of a group of circling white storks
      (Ciconia ciconia) throughout their migratory journey from Germany to Spain. We
      analysed individual high-resolution GPS trajectories of storks during circling
      events, and evaluated each bird's flight behaviour in relation to its flock
      members. Within the flock, we identified subgroups that synchronize their
      movements and coordinate switches in their circling direction within thermals.
      These switches in direction can be initiated by any individual of the subgroup,
      irrespective of how advanced its relative vertical position is, and occur at
      specific horizontal locations within the thermal allowing the storks to remain
      within the thermal. Using the motion of all flock members, we were able to
      examine the dynamic variation of airflow within the thermals and to determine the
      specific environmental conditions surrounding the flock. With an increasing
      amount of high-resolution GPS tracking, we may soon be able to use these animals
      as distributed sensors providing us with a new means to obtain a detailed
      knowledge of our environment.This article is part of the theme issue 'Collective
      movement ecology'.

PMID- 29581397
TI  - From single steps to mass migration: the problem of scale in the movement ecology
      of the Serengeti wildebeest.
AB  - A central question in ecology is how to link processes that occur over different
      scales. The daily interactions of individual organisms ultimately determine
      community dynamics, population fluctuations and the functioning of entire
      ecosystems. Observations of these multiscale ecological processes are constrained
      by various technological, biological or logistical issues, and there are often
      vast discrepancies between the scale at which observation is possible and the
      scale of the question of interest. Animal movement is characterized by processes
      that act over multiple spatial and temporal scales. Second-by-second decisions
      accumulate to produce annual movement patterns. Individuals influence, and are
      influenced by, collective movement decisions, which then govern the spatial
      distribution of populations and the connectivity of meta-populations. While the
      field of movement ecology is experiencing unprecedented growth in the
      availability of movement data, there remain challenges in integrating
      observations with questions of ecological interest. In this article, we present
      the major challenges of addressing these issues within the context of the
      Serengeti wildebeest migration, a keystone ecological phenomena that crosses
      multiple scales of space, time and biological complexity.This article is part of
      the theme issue 'Collective movement ecology'.

PMID- 29581398
TI  - Fitness trade-offs of group formation and movement by Thomson's gazelles in the
      Serengeti ecosystem.
AB  - Collective behaviours contributing to patterns of group formation and coordinated
      movement are common across many ecosystems and taxa. Their ubiquity is presumably
      due to altering interactions between individuals and their predators, resources
      and physical environment in ways that enhance individual fitness. On the other
      hand, fitness costs are also often associated with group formation. Modifications
      to these interactions have the potential to dramatically impact population-level
      processes, such as trophic interactions or patterns of space use in relation to
      abiotic environmental variation. In a wide variety of empirical systems and
      models, collective behaviour has been shown to enhance access to ephemeral
      patches of resources, reduce the risk of predation and reduce vulnerability to
      environmental fluctuation. Evolution of collective behaviour should accordingly
      depend on the advantages of collective behaviour weighed against the costs
      experienced at the individual level. As an illustrative case study, we consider
      the potential trade-offs on Malthusian fitness associated with patterns of group
      formation and movement by migratory Thomson's gazelles in the Serengeti
      ecosystem.This article is part of the theme issue 'Collective movement ecology'.

PMID- 29581399
TI  - Friendship across species borders: factors that facilitate and constrain
      heterospecific sociality.
AB  - Our understanding of animal sociality is based almost entirely on single-species
      sociality. Heterospecific sociality, although documented in numerous taxa and
      contexts, remains at the margins of sociality research and is rarely investigated
      in conjunction with single-species sociality. This could be because
      heterospecific and single-species sociality are thought to be based on
      fundamentally different mechanisms. However, our literature survey shows that
      heterospecific sociality based on mechanisms similar to single-species sociality
      is reported from many taxa, contexts and for various benefits. Therefore, we
      propose a conceptual framework to understand conspecific versus heterospecific
      social partner choice. Previous attempts, which are all in the context of social
      information, model partner choice as a trade-off between information benefit and
      competition cost, along a single phenotypic distance axis. Our framework of
      partner choice considers both direct grouping benefits and information benefits,
      allows heterospecific and conspecific partners to differ in degree and
      qualitatively, and uses a multi-dimensional trait space analysis of costs
      (competition and activity matching) and benefits (relevance of partner and
      quality of partner). We conclude that social partner choice is best-viewed as a
      continuum: some social benefits are obtainable only from conspecifics, some only
      from dissimilar heterospecifics, while many are potentially obtainable from
      conspecifics and heterospecifics.This article is part of the theme issue
      'Collective movement ecology'.

PMID- 29581400
TI  - Using activity and sociability to characterize collective motion.
AB  - A wide range of measurements can be made on the collective motion of groups, and
      the movement of individuals within them. These include, but are not limited to:
      group size, polarization, speed, turning speed, speed or directional
      correlations, and distances to near neighbours. From an ecological and
      evolutionary perspective, we would like to know which of these measurements
      capture biologically meaningful aspects of an animal's behaviour and contribute
      to its survival chances. Previous simulation studies have emphasized two main
      factors shaping individuals' behaviour in groups; attraction and alignment.
      Alignment responses appear to be important in transferring information between
      group members and providing synergistic benefits to group members. Likewise,
      attraction to conspecifics is thought to provide benefits through, for example,
      selfish herding. Here, we use a factor analysis on a wide range of simple
      measurements to identify two main axes of collective motion in guppies (Poecilia
      reticulata): (i) sociability, which corresponds to attraction (and to a lesser
      degree alignment) to neighbours, and (ii) activity, which combines alignment with
      directed movement. We show that for guppies, predation in a natural environment
      produces higher degrees of sociability and (in females) lower degrees of
      activity, while female guppies sorted for higher degrees of collective alignment
      have higher degrees of both sociability and activity. We suggest that the
      activity and sociability axes provide a useful framework for measuring the
      behaviour of animals in groups, allowing the comparison of individual and
      collective behaviours within and between species.This article is part of the
      theme issue 'Collective movement ecology'.

PMID- 29581401
TI  - Migration in the Anthropocene: how collective navigation, environmental system
      and taxonomy shape the vulnerability of migratory species.
AB  - Recent increases in human disturbance pose significant threats to migratory
      species using collective movement strategies. Key threats to migrants may differ
      depending on behavioural traits (e.g. collective navigation), taxonomy and the
      environmental system (i.e. freshwater, marine or terrestrial) associated with
      migration. We quantitatively assess how collective navigation, taxonomic
      membership and environmental system impact species' vulnerability by (i)
      evaluating population change in migratory and non-migratory bird, mammal and fish
      species using the Living Planet Database (LPD), (ii) analysing the role of
      collective navigation and environmental system on migrant extinction risk using
      International Union for Conservation of Nature (IUCN) classifications and (iii)
      compiling literature on geographical range change of migratory species.
      Likelihood of population decrease differed by taxonomic group: migratory birds
      were more likely to experience annual declines than non-migrants, while mammals
      displayed the opposite pattern. Within migratory species in IUCN, we observed
      that collective navigation and environmental system were important predictors of
      extinction risk for fishes and birds, but not for mammals, which had overall
      higher extinction risk than other taxa. We found high phylogenetic relatedness
      among collectively navigating species, which could have obscured its importance
      in determining extinction risk. Overall, outputs from these analyses can help
      guide strategic interventions to conserve the most vulnerable migrations.This
      article is part of the theme issue 'Collective movement ecology'.

PMID- 29581402
TI  - Eco-evolutionary dynamics, density-dependent dispersal and collective behaviour:
      implications for salmon metapopulation robustness.
AB  - The spatial dispersal of individuals plays an important role in the dynamics of
      populations, and is central to metapopulation theory. Dispersal provides
      connections within metapopulations, promoting demographic and evolutionary
      rescue, but may also introduce maladapted individuals, potentially lowering the
      fitness of recipient populations through introgression of heritable traits. To
      explore this dual nature of dispersal, we modify a well-established eco
      evolutionary model of two locally adapted populations and their associated mean
      trait values, to examine recruiting salmon populations that are connected by
      density-dependent dispersal, consistent with collective migratory behaviour that
      promotes navigation. When the strength of collective behaviour is weak such that
      straying is effectively constant, we show that a low level of straying is
      associated with the highest gains in metapopulation robustness and that high
      straying serves to erode robustness. Moreover, we find that as the strength of
      collective behaviour increases, metapopulation robustness is enhanced, but this
      relationship depends on the rate at which individuals stray. Specifically, strong
      collective behaviour increases the presence of hidden low-density basins of
      attraction, which may serve to trap disturbed populations, and this is
      exacerbated by increased habitat heterogeneity. Taken as a whole, our findings
      suggest that density-dependent straying and collective migratory behaviour may
      help metapopulations, such as in salmon, thrive in dynamic landscapes. Given the
      pervasive eco-evolutionary impacts of dispersal on metapopulations, these
      findings have important ramifications for the conservation of salmon
      metapopulations facing both natural and anthropogenic contemporary
      disturbances.This article is part of the theme issue 'Collective movement
      ecology'.

PMID- 29581403
TI  - Personality and the collective: bold homing pigeons occupy higher leadership
      ranks in flocks.
AB  - While collective movement is ecologically widespread and conveys numerous
      benefits on individuals, it also poses a coordination problem: who controls the
      group's movements? The role that animal 'personalities' play in this question has
      recently become a focus of research interest. Although many animal groups have
      distributed leadership (i.e. multiple individuals influence collective
      decisions), studies linking personality and leadership have focused predominantly
      on the group's single most influential individual. In this study, we investigate
      the relationship between personality and the influence of multiple leaders on
      collective movement using homing pigeons, Columba livia, a species known to
      display complex multilevel leadership hierarchies during flock flights. Our
      results show that more exploratory (i.e. 'bold') birds are more likely to occupy
      higher ranks in the leadership hierarchy and thus have more influence on the
      direction of collective movement than less exploratory (i.e. 'shy') birds during
      both free flights around their lofts and homing flights from a distant site. Our
      data also show that bold pigeons fly faster than shy birds during solo flights.
      We discuss our results in light of theories about the evolution of personality,
      with specific reference to the adaptive value of heterogeneity in animal
      groups.This article is part of the theme issue 'Collective movement ecology'.

PMID- 29581404
TI  - Inferring the rules of social interaction in migrating caribou.
AB  - Social interactions are a significant factor that influence the decision-making
      of species ranging from humans to bacteria. In the context of animal migration,
      social interactions may lead to improved decision-making, greater ability to
      respond to environmental cues, and the cultural transmission of optimal routes.
      Despite their significance, the precise nature of social interactions in
      migrating species remains largely unknown. Here we deploy unmanned aerial systems
      to collect aerial footage of caribou as they undertake their migration from
      Victoria Island to mainland Canada. Through a Bayesian analysis of trajectories
      we reveal the fine-scale interaction rules of migrating caribou and show they are
      attracted to one another and copy directional choices of neighbours, but do not
      interact through clearly defined metric or topological interaction ranges. By
      explicitly considering the role of social information on movement decisions we
      construct a map of near neighbour influence that quantifies the nature of
      information flow in these herds. These results will inform more realistic,
      mechanism-based models of migration in caribou and other social ungulates,
      leading to better predictions of spatial use patterns and responses to changing
      environmental conditions. Moreover, we anticipate that the protocol we developed
      here will be broadly applicable to study social behaviour in a wide range of
      migratory and non-migratory taxa.This article is part of the theme issue
      'Collective movement ecology'.

PMID- 29581405
TI  - Lung abscess or empyema? Taking a closer look.

PMID- 29581406
TI  - Staphylococcus aureus utilizes host-derived lipoprotein particles as sources of
      exogenous fatty acids.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a threat to global health.
      Consequently, much effort has focused on the development of new antimicrobials
      that target novel aspects of S. aureus physiology. Fatty acids are required to
      maintain cell viability, and bacteria synthesize fatty acids using the type II
      fatty acid synthesis pathway (FASII). FASII is significantly different from human
      fatty acid synthesis, underscoring the therapeutic potential of inhibiting this
      pathway. However, many Gram-positive pathogens incorporate exogenous fatty acids,
      bypassing FASII inhibition and leaving the clinical potential of FASII inhibitors
      uncertain. Importantly, the source(s) of fatty acids available to pathogens
      within the host environment remains unclear. Fatty acids are transported
      throughout the body by lipoprotein particles in the form of triglycerides and
      esterified cholesterol. Thus, lipoproteins, such as low-density lipoprotein (LDL)
      represent a potentially rich source of exogenous fatty acids for S. aureus during
      infection. We sought to test the ability of LDLs to serve as a fatty acid source
      for S. aureus and show that cells cultured in the presence of human LDLs
      demonstrate increased tolerance to the FASII inhibitor, triclosan. Using mass
      spectrometry, we observed that host-derived fatty acids present in the LDLs are
      incorporated into the staphylococcal membrane and that tolerance to triclosan is
      facilitated by the fatty acid kinase A, FakA, and Geh, a triacylglycerol lipase.
      Finally, we demonstrate that human LDLs support the growth of S. aureus fatty
      acid auxotrophs. Together, these results suggest that human lipoprotein particles
      are a viable source of exogenous fatty acids for S. aureus during
      infection.IMPORTANCE Inhibition of bacterial fatty acid synthesis is a promising
      approach to combating infections caused by S. aureus and other human pathogens.
      However, S. aureus incorporates exogenous fatty acids into its phospholipid
      bilayer. Therefore, the clinical utility of targeting bacterial fatty acid
      synthesis is debated. Moreover, the fatty acid reservoir(s) exploited by S.
      aureus are not well understood. Human low-density lipoprotein particles represent
      a particularly abundant in vivo source of fatty acids and are present in tissues
      S. aureus colonizes. Herein, we establish that S. aureus is capable of utilizing
      the fatty acids present in low-density lipoproteins to bypass both chemical and
      genetic inhibition of fatty acid synthesis. These findings imply that S. aureus
      targets LDLs as a source of fatty acids during pathogenesis.

PMID- 29581407
TI  - A Critical Region in the FlaA Flagellin Facilitates Filament Formation of the
      Vibrio cholerae Flagellum.
AB  - Vibrio cholerae is a Gram-negative bacterium with a monotrichous flagellum that
      causes the human disease cholera. Flagellum-mediated motility is an integral part
      of the bacterial life cycle inside the host and in the aquatic environment. The
      V. cholerae flagellar filament is composed of five flagellin subunits (FlaA,
      FlaB, FlaC, FlaD, and FlaE); however, only FlaA is necessary and sufficient for
      filament synthesis. flaA is transcribed from a class III flagellar promoter,
      whereas the other four flagellins are transcribed from class IV promoters.
      However, expressing flaA from a class IV promoter still facilitated motility in a
      strain that was otherwise lacking all five flagellins (DeltaflaA-E). Furthermore,
      FlaA from V. parahaemolyticus (FlaAVP; 77% identity) supported motility of the V.
      cholerae DeltaflaA-E strain, whereas FlaA from V. vulnificus (FlaAVV; 75%
      identity) did not, indicating that FlaA amino acid sequence is responsible for
      its critical role in flagellar synthesis. Chimeric proteins composed of different
      domains of FlaAVC and FlaD or FlaAVV revealed that the N-terminal D1 domain (D1N)
      contains an important region required for FlaA function. Further analyses of
      chimeric FlaAVC-FlaD proteins identified a lysine residue present at position 145
      of the other flagellins but absent from FlaAVC that can prevent monofilament
      formation. Moreover, the D1N region of amino acids 87 to 153 of FlaAVV inserted
      into FlaAVC allows monofilament formation but not motility, apparently due to the
      lack of filament curvature. These results identify residues within the D1N domain
      that allow FlaAVC to fold into a functional filament structure and suggest that
      FlaAVC assists correct folding of the other flagellins.IMPORTANCEV. cholerae
      causes the severe diarrheal disease cholera. Its ability to swim is mediated by
      rotation of a polar flagellum, and this motility is integral to its ability to
      cause disease and persist in the environment. The current studies illuminate how
      one specific flagellin (FlaA) within a multiflagellin structure mediates
      formation of the flagellar filament, thus allowing V. cholerae to swim. This
      knowledge can lead to safer vaccines and potential therapeutics to inhibit
      cholera.

PMID- 29581409
TI  - One Intact Transmembrane Substrate Binding Site Is Sufficient for the Function of
      the Homodimeric Type I ATP-Binding Cassette Importer for Positively Charged Amino
      Acids Art(MP)2 of Geobacillus stearothermophilus.
AB  - ATP-binding cassette (ABC) transport systems comprise two transmembrane
      domains/subunits that form a translocation path and two nucleotide-binding
      domains/subunits that bind and hydrolyze ATP. Prokaryotic canonical ABC import
      systems require an extracellular substrate-binding protein for function.
      Knowledge of substrate-binding sites within the transmembrane subunits is scarce.
      Recent crystal structures of the ABC importer Art(QN)2 for positively charged
      amino acids of Thermoanerobacter tengcongensis revealed the presence of one
      substrate molecule in a defined binding pocket in each of the transmembrane
      subunits, ArtQ (J. Yu, J. Ge, J. Heuveling, E. Schneider, and M. Yang, Proc Natl
      Acad Sci U S A 112:5243-5248, 2015, https://doi.org/10.1073/pnas.1415037112).
      This finding raised the question of whether both sites must be loaded with
      substrate prior to initiation of the transport cycle. To address this matter, we
      first explored the role of key residues that form the binding pocket in the
      closely related Art(MP)2 transporter of Geobacillus stearothermophilus, by
      monitoring consequences of mutations in ArtM on ATPase and transport activity at
      the level of purified proteins embedded in liposomes. Our results emphasize that
      two negatively charged residues (E153 and D160) are crucial for wild-type
      function. Furthermore, the variant Art[M(L67D)P]2 exhibited strongly impaired
      activities, which is why it was considered for construction of a hybrid complex
      containing one intact and one impaired substrate-binding site. Activity assays
      clearly revealed that one intact binding site was sufficient for function. To our
      knowledge, our study provides the first biochemical evidence on transmembrane
      substrate-binding sites of an ABC importer.IMPORTANCE Canonical prokaryotic ATP
      binding cassette importers mediate the uptake of a large variety of chemicals,
      including nutrients, osmoprotectants, growth factors, and trace elements. Some
      also play a role in bacterial pathogenesis, which is why full understanding of
      their mode of action is of the utmost importance. One of the unsolved problems
      refers to the chemical nature and number of substrate binding sites formed by the
      transmembrane subunits. Here, we report that a hybrid amino acid transporter of
      G. stearothermophilus, encompassing one intact and one impaired transmembrane
      binding site, is fully competent in transport, suggesting that the binding of one
      substrate molecule is sufficient to trigger the translocation process.

PMID- 29581408
TI  - The Opp (AmiACDEF) Oligopeptide Transporter Mediates Resistance of Serotype 2
      Streptococcus pneumoniae D39 to Killing by Chemokine CXCL10 and Other
      Antimicrobial Peptides.
AB  - Antimicrobial peptides (AMPs), including chemokines, are produced during
      infections to kill pathogenic bacteria. To fill in gaps in knowledge about the
      sensitivities of Streptococcus pneumoniae and related Streptococcus species to
      chemokines and AMPs, we performed a systematic, quantitative study of inhibition
      by chemokine CXCL10 and the AMPs LL-37 and nisin. In a standard Tris-glucose
      buffer (TGS), all strains assayed lacked metabolic activity, as determined by
      resazurin (alamarBlue) reduction, and were extremely sensitive to CXCL10 and AMPs
      (50% inhibitory concentration [IC50], ~0.04 MUM). In TGS, changes in
      sensitivities caused by mutations were undetectable. In contrast, strains that
      retained reductive metabolic activity in a different assay buffer (NPB [10 mM
      sodium phosphate {pH 7.4}, 1% {vol/vol} brain heart infusion {BHI} broth]) were
      less sensitive to CXCL10 and AMPs than in TGS. In NPB, mutants known to respond
      to AMPs, such as Deltadlt mutants lacking d-alanylation of teichoic acids,
      exhibited the expected increased sensitivity. S. pneumoniae serotype 2 strain D39
      was much (~10-fold) less sensitive to CXCL10 killing in NPB than serotype 4
      strain TIGR4, and the sensitivity of TIGR4 was unaffected by the absence of
      capsule. Candidate screening of strain D39 revealed that mutants lacking Opp
      (DeltaamiACDEF) oligopeptide permease were significantly more resistant to CXCL10
      than the wild-type strain. This increased resistance could indicate that Opp is a
      target for CXCL10 binding or that it transports CXCL10 into cells. Finally,
      DeltaftsX or DeltaftsE mutants of Bacillus subtilis or amino acid changes that
      interfere with FtsX function in S. pneumoniae did not impart resistance to
      CXCL10, in contrast to previous results for Bacillus anthracis, indicating that
      FtsX is not a general target for CXCL10 binding.IMPORTANCES. pneumoniae
      (pneumococcus) is a human commensal bacterium and major opportunistic respiratory
      pathogen that causes serious invasive diseases, killing millions of people
      worldwide annually. Because of its increasing antibiotic resistance, S.
      pneumoniae is now listed as a "superbug" for which new antibiotics are urgently
      needed. This report fills in knowledge gaps and resolves inconsistencies in the
      scientific literature about the sensitivity of S. pneumoniae and related
      Streptococcus pathogens to chemokines and AMPs. It also reveals a new mechanism
      by which S. pneumoniae can acquire resistance to chemokine CXCL10. This mechanism
      involves the Opp (AmiACDEF) oligopeptide transporter, which plays additional
      pleiotropic roles in pneumococcal physiology, quorum sensing, and virulence.
      Taking the results together, this work provides new information about the way
      chemokines kill pneumococcal cells.

PMID- 29581410
TI  - Environmental role of pathogenic traits in Vibrio cholerae.
AB  - Vibrio cholerae is a natural inhabitant of aquatic ecosystems. Some strains of V.
      cholerae can colonize the human host and cause cholera, a profuse watery
      diarrhea. The major pathogenicity factors and virulence regulators of V. cholerae
      are either encoded in mobile genetic elements acquired in the environment (e.g.
      pathogenicity islands or lysogenic phages) or in the core genome. Several lines
      of evidence indicate that the emergence of numerous virulence traits of V.
      cholerae occurred in its natural environment due to biotic and abiotic pressures.
      Here, we discuss the connection between the human host and the potential
      ecological role of these virulent traits. Unraveling these connections will help
      us understand the emergence of this organism and other facultative bacterial
      pathogens.

PMID- 29581413
TI  - Visible-light promoted catalytic activity of dumbbell-like Au nanorods supported
      on graphene/TiO2 sheets towards hydrogenation reaction.
AB  - In this work, the rationally-designed sharp corners on Au nanorods tremendously
      improved the catalytic activity, particularly in the presence of visible light
      irradiation, towards the hydrogenation of 4-nitrophenol to 4-aminophenol. A
      strikingly increased rate constant of 50.6 g-1 s-1 L was achieved in M-Au-3,
      which was 41.8 times higher than that of parent Au nanorods under dark
      conditions. The enhanced activities were proportional to the extent of the
      protruding sharp corners. Furthermore, remarkably enhanced activities were
      achieved in novel ternary Au/RGO/TiO2 sheets, which were endowed with a 52.0
      times higher rate constant than that of straight Au nanorods. These remarkably
      enhanced activities were even higher than those of previously reported 3-5 nm Au
      and 3 nm Pt nanoparticles. It was systematically observed that there are three
      aspects to the synergistic effects between Au and RGO sheets: (i) electron
      transfer from RGO to Au, (ii) a high concentration of p-nitrophenol close to
      dumbbell-like Au nanorods on RGO sheets, and (iii) increased local reaction
      temperature from the photothermal effect of both dumbbell-like Au nanorods and
      RGO sheets.

PMID- 29581411
TI  - The Transcriptional Regulator BpsR Controls the Growth of Bordetella
      bronchiseptica by Repressing Genes Involved in Nicotinic Acid Degradation.
AB  - Many of the pathogenic species of the genus Bordetella have an absolute
      requirement for nicotinic acid (NA) for laboratory growth. These Gram-negative
      bacteria also harbor a gene cluster homologous to the nic cluster of Pseudomonas
      putida which is involved in the aerobic degradation of NA and its transcriptional
      control. We report here that BpsR, a negative regulator of biofilm formation and
      Bps polysaccharide production, controls the growth of Bordetella bronchiseptica
      by repressing the expression of nic genes. The severe growth defect of the
      DeltabpsR strain in Stainer-Scholte medium was restored by supplementation with
      NA, which also functioned as an inducer of nic genes at low micromolar
      concentrations that are usually present in animals and humans. Purified BpsR
      protein bound to the nic promoter region, and its DNA binding activity was
      inhibited by 6-hydroxynicotinic acid (6-HNA), the first metabolite of the NA
      degradative pathway. Reporter assays with the isogenic mutant derivative of the
      wild-type (WT) strain harboring deletion in nicA, which encodes a putative
      nicotinic acid hydroxylase responsible for conversion of NA to 6-HNA, showed that
      6-HNA is the actual inducer of the nic genes in the bacterial cell. Gene
      expression profiling further showed that BpsR dually activated and repressed the
      expression of genes associated with pathogenesis, transcriptional regulation,
      metabolism, and other cellular processes. We discuss the implications of these
      findings with respect to the selection of pyridines such as NA and quinolinic
      acid for optimum bacterial growth depending on the ecological niche.IMPORTANCE
      BpsR, the previously described regulator of biofilm formation and Bps
      polysaccharide production, controls Bordetella bronchiseptica growth by
      regulating the expression of genes involved in the degradation of nicotinic acid
      (NA). 6-Hydroxynicotinic acid (6-HNA), the first metabolite of the NA degradation
      pathway prevented BpsR from binding to DNA and was the actual in vivo inducer. We
      hypothesize that BpsR enables Bordetella bacteria to efficiently and selectively
      utilize NA for their survival depending on the environment in which they reside.
      The results reported herein lay the foundation for future investigations of how
      BpsR and the alteration of its activity by NA orchestrate the control of
      Bordetella growth, metabolism, biofilm formation, and pathogenesis.

PMID- 29581412
TI  - HnRNP L represses cryptic exons.
AB  - The fidelity of RNA splicing is regulated by a network of splicing enhancers and
      repressors, although the rules that govern this process are not yet fully
      understood. One mechanism that contributes to splicing fidelity is the repression
      of nonconserved cryptic exons by splicing factors that recognize dinucleotide
      repeats. We previously identified that TDP-43 and PTBP1/PTBP2 are capable of
      repressing cryptic exons utilizing UG and CU repeats, respectively. Here we
      demonstrate that hnRNP L (HNRNPL) also represses cryptic exons by utilizing
      exonic CA repeats, particularly near the 5'SS. We hypothesize that hnRNP L
      regulates CA repeat repression for both cryptic exon repression and developmental
      processes such as T cell differentiation.

PMID- 29581415
TI  - Retracted: Seropositivity and Titers of Anti-Smooth Muscle Actin Antibody Are
      Associated with Relapse of Type 1 Autoimmune Hepatitis.

PMID- 29581414
TI  - Nephrectomy Versus Embolization of Non-Functioning Renal Graft: A Systematic
      Review with a Proportional Meta-Analysis.
AB  - There is no standardization on the timing of the best approach to treat a non
      functioning renal graft. We reviewed the literature and performed a proportional
      meta-analysis of case series of transplantectomy and embolization for a non
      functioning renal graft. The groups were compared for mortality and morbidity
      outcomes. A total of 2421 patients were included in this review. Of these, 2232
      patients underwent transplantectomy and 189 underwent percutaneous embolization.
      The mortality rate in the nephrectomy group was 4% [95% confidence interval [CI],
      2-7%; I2=87%] as compared with 0.1% [95% CI, 0.1-0.5%; I2=0%] in the embolization
      group. The rates of common morbidities were 18% [95% CI, 13-26%, I2=79.7%] for
      nephrectomy compared with 1.2% [95% CI, 0.7-2.1%, I2=26.4%] for embolization. The
      incidence of post-embolization syndrome was 68%, and 20% of patients needed post
      embolization nephrectomy. Percutaneous embolization was associated with lower
      mortality and morbidity rates but also with a high rate of post-embolization
      syndrome. However, in most cases this complication had easily manageable
      symptoms. Embolization is a new and attractive technique that can be considered
      in treating non-functioning renal grafts.

PMID- 29581416
TI  - Plasma Levels of Homocysteine and the Occurrence and Progression of Rectal
      Cancer.

PMID- 29581417
TI  - Resolution of Infliximab-Refractory Nivolumab-Induced Acute Severe Enterocolitis
      After Cyclosporine Treatment in a Patient with Non-Small Cell Lung Cancer.
AB  - BACKGROUND Enterocolitis is an immune-related adverse event associated with
      nivolumab treatment. Although intravenous corticosteroids and infliximab are
      recommended as a first-line and second-line therapy, respectively, there is no
      established treatment for severe enterocolitis that is refractory to these drugs.
      CASE REPORT A 62-year-old male with non-small cell lung cancer, with multiple
      brain metastasis, received nivolumab as the eighth-line chemotherapy for his
      disease. A few days after nivolumab administration, grade 2-3 enterocolitis
      developed in the patient. The enterocolitis improved to grade 1 after careful
      observation; however, it was aggravated to grade 3 after resuming nivolumab
      treatment. After cessation of nivolumab, 3.3 mg of intravenous dexamethasone and
      40 mg of methylprednisolone were administered for 16 days and subsequently 30-60
      mg of oral prednisolone was administered for 50 days, with little improvement in
      the patient's colitis. A second-line treatment with 5 mg/kg of infliximab was
      twice attempted, but the patient had persistent diarrhea. Therefore, 50 mg of
      oral cyclosporine was started as a third-line therapy. Three days after the start
      of cyclosporine, the number of diarrhea events decreased, with resolution 2 weeks
      after cyclosporine administration. CONCLUSIONS Oral cyclosporine treatment can be
      a third-line therapy for enterocolitis associated with immune-related adverse
      events.

PMID- 29581418
TI  - Limited Dynamic Hip Screw for Treatment of Intertrochanteric Fractures: A
      Biomechanical Study.

PMID- 29581419
TI  - Large-area and bright pulsed electroluminescence in monolayer semiconductors.
AB  - Transition-metal dichalcogenide monolayers have naturally terminated surfaces and
      can exhibit a near-unity photoluminescence quantum yield in the presence of
      suitable defect passivation. To date, steady-state monolayer light-emitting
      devices suffer from Schottky contacts or require complex heterostructures. We
      demonstrate a transient-mode electroluminescent device based on transition-metal
      dichalcogenide monolayers (MoS2, WS2, MoSe2, and WSe2) to overcome these
      problems. Electroluminescence from this dopant-free two-terminal device is
      obtained by applying an AC voltage between the gate and the semiconductor.
      Notably, the electroluminescence intensity is weakly dependent on the Schottky
      barrier height or polarity of the contact. We fabricate a monolayer seven-segment
      display and achieve the first transparent and bright millimeter-scale light
      emitting monolayer semiconductor device.

PMID- 29581420
TI  - Aberrant salience network functional connectivity in auditory verbal
      hallucinations: a first episode psychosis sample.
AB  - Auditory verbal hallucinations (AVH) often lead to distress and functional
      disability, and are frequently associated with psychotic illness. Previously both
      state and trait magnetic resonance imaging (MRI) studies of AVH have identified
      activity in brain regions involving auditory processing, language, memory and
      areas of default mode network (DMN) and salience network (SN). Current evidence
      is clouded by research mainly in participants on long-term medication, with
      chronic illness and by choice of seed regions made 'a priori'. Thus, the aim of
      this study was to elucidate the intrinsic functional connectivity in patients
      presenting with first episode psychosis (FEP). Resting state functional MRI data
      were available from 18 FEP patients, 9 of whom also experienced AVH of sufficient
      duration in the scanner and had symptom capture functional MRI (sc fMRI),
      together with 18 healthy controls. Symptom capture results were used to
      accurately identify specific brain regions active during AVH; including the
      superior temporal cortex, insula, precuneus, posterior cingulate and
      parahippocampal complex. Using these as seed regions, patients with FEP and AVH
      showed increased resting sb-FC between parts of the SN and the DMN and between
      the SN and the cerebellum, but reduced sb-FC between the claustrum and the
      insula, compared to healthy controls.It is possible that aberrant activity within
      the DMN and SN complex may be directly linked to impaired salience appraisal of
      internal activity and AVH generation. Furthermore, decreased intrinsic functional
      connectivity between the claustrum and the insula may lead to compensatory over
      activity in parts of the auditory network including areas involved in DMN,
      auditory processing, language and memory, potentially related to the complex and
      individual content of AVH when they occur.

PMID- 29581421
TI  - Lateral habenula perturbation reduces default-mode network connectivity in a rat
      model of depression.
AB  - Hyperconnectivity of the default-mode network (DMN) is one of the most widely
      replicated neuroimaging findings in major depressive disorder (MDD). Further,
      there is growing evidence for a central role of the lateral habenula (LHb) in the
      pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb
      and the DMN, but no causal relationship has been shown to date. We combined
      optogenetics and functional magnetic resonance imaging (fMRI), to establish a
      causal relationship, using an animal model of treatment-resistant depression,
      namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion
      channel was introduced into the LHb by viral transduction. Subsequently, laser
      stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner.
      Neural activity and connectivity were assessed, before, during and after laser
      stimulation. We observed a connectivity decrease in the DMN following laser
      induced LHb perturbation. Our data indicate a causal link between LHb
      downregulation and reduction in DMN connectivity. These findings may advance our
      mechanistic understanding of LHb inhibition, which had previously been identified
      as a promising therapeutic principle, especially for treatment-resistant
      depression.

PMID- 29581422
TI  - Low-frequency and rare variants may contribute to elucidate the genetics of major
      depressive disorder.
AB  - Major depressive disorder (MDD) is a common but serious psychiatric disorder with
      significant levels of morbidity and mortality. Recent genome-wide association
      studies (GWAS) on common variants increase our understanding of MDD; however, the
      underlying genetic basis remains largely unknown. Many studies have been proposed
      to explore the genetics of complex diseases from a viewpoint of the "missing
      heritability" by considering low-frequency and rare variants, copy-number
      variations, and other types of genetic variants. Here we developed a novel
      computational and statistical strategy to investigate the "missing heritability"
      of MDD. We applied Hamming distance on common, low-frequency, and rare single
      nucleotide polymorphism (SNP) sets to measure genetic distance between two
      individuals, and then built the multi-dimensional scaling (MDS) pictures. Whole
      exome genotyping data from a Los Angeles Mexican-American cohort (203 MDD and 196
      controls) and a European-ancestry cohort (473 MDD and 497 controls) were examined
      using our proposed methodology. MDS plots showed very significant separations
      between MDD cases and healthy controls for low-frequency SNP set (P value < 2.2e
      16) and rare SNP set (P value = 7.681e-12). Our results suggested that low
      frequency and rare variants may play more significant roles in the genetics of
      MDD.

PMID- 29581423
TI  - Effects on gene expression and behavior of untagged short tandem repeats: the
      case of arginine vasopressin receptor 1a (AVPR1a) and externalizing behaviors.
AB  - Genome-wide association studies (GWAS) of complex, heritable, behavioral
      phenotypes have yielded an incomplete accounting of the genetic influences. The
      identified loci explain only a portion of the observed heritability, and few of
      the loci have been shown to be functional. It is clear that current GWAS
      techniques overlook key components of phenotypically relevant genetic variation,
      either because of sample size, as is frequently asserted, or because of
      methodology. Here we use arginine vasopressin receptor 1a (AVPR1a) as an in-depth
      model of a methodologic limitation of GWAS: the functional genetic variation (in
      the form of short tandem repeats) of this key gene involved in affiliative
      behavior cannot be captured by current GWAS methodologies. Importantly, we find
      evidence of differential allele expression, twofold or more, in at least a third
      of human brain samples heterozygous for a reporter SNP in the AVPR1a transcript.
      We also show that this functional effect and a downstream phenotype,
      externalizing behavior, are predicted by AVPR1a STRs but not SNPs.

PMID- 29581424
TI  - A comprehensive map coupling histone modifications with gene regulation in adult
      dopaminergic and serotonergic neurons.
AB  - The brain is composed of hundreds of different neuronal subtypes, which largely
      retain their identity throughout the lifespan of the organism. The mechanisms
      governing this stability are not fully understood, partly due to the diversity
      and limited size of clinically relevant neuronal populations, which constitute a
      technical challenge for analysis. Here, using a strategy that allows for ChIP-seq
      combined with RNA-seq in small neuronal populations in vivo, we present a
      comparative analysis of permissive and repressive histone modifications in adult
      midbrain dopaminergic neurons, raphe nuclei serotonergic neurons, and embryonic
      neural progenitors. Furthermore, we utilize the map generated by our analysis to
      show that the transcriptional response of midbrain dopaminergic neurons following
      6-OHDA or methamphetamine injection is characterized by increased expression of
      genes with promoters dually marked by H3K4me3/H3K27me3. Our study provides an in
      vivo genome-wide analysis of permissive/repressive histone modifications coupled
      to gene expression in these rare neuronal subtypes.

PMID- 29581425
TI  - Dissociating frontoparietal brain networks with neuroadaptive Bayesian
      optimization.
AB  - Understanding the unique contributions of frontoparietal networks (FPN) in
      cognition is challenging because they overlap spatially and are co-activated by
      diverse tasks. Characterizing these networks therefore involves studying their
      activation across many different cognitive tasks, which previously was only
      possible with meta-analyses. Here, we use neuroadaptive Bayesian optimization, an
      approach combining real-time analysis of functional neuroimaging data with
      machine-learning, to discover cognitive tasks that segregate ventral and dorsal
      FPN activity. We identify and subsequently refine two cognitive tasks, Deductive
      Reasoning and Tower of London, which maximally dissociate the dorsal from ventral
      FPN. We subsequently investigate these two FPNs in the context of a wider range
      of FPNs and demonstrate the importance of studying the whole activity profile
      across tasks to uniquely differentiate any FPN. Our findings deviate from
      previous meta-analyses and hypothesized functional labels for these FPNs. Taken
      together the results form the starting point for a neurobiologically-derived
      cognitive taxonomy.

PMID- 29581426
TI  - A semi-synthetic regulon enables rapid growth of yeast on xylose.
AB  - Nutrient assimilation is the first step that allows biological systems to
      proliferate and produce value-added products. Yet, implementation of heterologous
      catabolic pathways has so far relied on constitutive gene expression without
      consideration for global regulatory systems that may enhance nutrient
      assimilation and cell growth. In contrast, natural systems prefer nutrient
      responsive gene regulation (called regulons) that control multiple cellular
      functions necessary for cell survival and growth. Here, in Saccharomyces
      cerevisiae, by partially- and fully uncoupling galactose (GAL)-responsive
      regulation and metabolism, we demonstrate the significant growth benefits
      conferred by the GAL regulon. Next, by adapting the various aspects of the GAL
      regulon for a non-native nutrient, xylose, we build a semi-synthetic regulon that
      exhibits higher growth rate, better nutrient consumption, and improved growth
      fitness compared to the traditional and ubiquitous constitutive expression
      strategy. This work provides an elegant paradigm to integrate non-native nutrient
      catabolism with native, global cellular responses to support fast growth.

PMID- 29581427
TI  - TRIM11 activates the proteasome and promotes overall protein degradation by
      regulating USP14.
AB  - The proteasome is a complex protease critical for protein quality control and
      cell regulation, and its dysfunction is associated with cancer and other
      diseases. However, the mechanisms that control proteasome activity  in normal and
      malignant cells remain unclear. Here we report that TRIM11 enhances degradation
      of aberrant and normal regulatory proteins, and augments overall rate of
      proteolysis. Mechanistically, TRIM11 binds to both the proteasome and USP14, a
      deubiquitinase that prematurely removes ubiquitins from proteasome-bound
      substrates and also noncatalytically inhibits the proteasome, and precludes their
      association, thereby increasing proteasome activity. TRIM11 promotes cell
      survival and is upregulated upon heat shock. Moreover, TRIM11 is required for
      tumor growth, and increased expression of TRIM11 correlates with poor clinical
      survival. These findings identify TRIM11 as an important activator of the
      proteasome, define a pathway that adjusts proteasome activity, and reveal a
      mechanism by which tumor cells acquire higher degradative power to support
      oncogenic growth.

PMID- 29581428
TI  - Divergent midbrain circuits orchestrate escape and freezing responses to looming
      stimuli in mice.
AB  - Animals respond to environmental threats, e.g. looming visual stimuli, with
      innate defensive behaviors such as escape and freezing. The key neural circuits
      that participate in the generation of such dimorphic defensive behaviors remain
      unclear. Here we show that the dimorphic behavioral patterns triggered by looming
      visual stimuli are mediated by parvalbumin-positive (PV+) projection neurons in
      mouse superior colliculus (SC). Two distinct groups of SC PV+ neurons form
      divergent pathways to transmit threat-relevant visual signals to neurons in the
      parabigeminal nucleus (PBGN) and lateral posterior thalamic nucleus (LPTN).
      Activations of PV+ SC-PBGN and SC-LPTN pathways mimic the dimorphic defensive
      behaviors. The PBGN and LPTN neurons are co-activated by looming visual stimuli.
      Bilateral inactivation of either nucleus results in the defensive behavior
      dominated by the other nucleus. Together, these data suggest that the SC
      orchestrates dimorphic defensive behaviors through two separate tectofugal
      pathways that may have interactions.

PMID- 29581429
TI  - Single rhodium atoms anchored in micropores for efficient transformation of
      methane under mild conditions.
AB  - Catalytic transformation of CH4 under a mild condition is significant for
      efficient utilization of shale gas under the circumstance of switching raw
      materials of chemical industries to shale gas. Here, we report the transformation
      of CH4 to acetic acid and methanol through coupling of CH4, CO and O2 on single
      site Rh1O5 anchored in microporous aluminosilicates in solution at <=150  degrees
      C. The activity of these singly dispersed precious metal sites for production of
      organic oxygenates can reach about 0.10 acetic acid molecules on a Rh1O5 site per
      second at 150  degrees C with a selectivity of ~70% for production of acetic
      acid. It is higher than the activity of free Rh cations by >1000 times.
      Computational studies suggest that the first C-H bond of CH4 is activated by
      Rh1O5 anchored on the wall of micropores of ZSM-5; the formed CH3 then couples
      with CO and OH, to produce acetic acid over a low activation barrier.

PMID- 29581430
TI  - LFP beta amplitude is linked to mesoscopic spatio-temporal phase patterns.
AB  - Beta oscillations observed in motor cortical local field potentials (LFPs)
      recorded on separate electrodes of a multi-electrode array have been shown to
      exhibit non-zero phase shifts that organize into planar waves. Here, we
      generalize this concept to additional classes of salient patterns that fully
      describe the spatial organization of beta oscillations. During a delayed reach-to
      grasp task we distinguish planar, synchronized, random, circular, and radial
      phase patterns in monkey primary motor and dorsal premotor cortices. We observe
      that patterns correlate with the beta amplitude (envelope): Coherent
      planar/radial wave propagation accelerates with growing amplitude, and
      synchronized patterns are observed at largest amplitudes. In contrast, incoherent
      random or circular patterns are observed almost exclusively when beta is strongly
      attenuated. The occurrence probability of a particular pattern modulates with
      behavioral epochs in the same way as beta amplitude: Coherent patterns are more
      present during movement preparation where amplitudes are large, while incoherent
      phase patterns are dominant during movement execution where amplitudes are small.
      Thus, we uncover a trigonal link between the spatial arrangement of beta phases,
      beta amplitude, and behavior. Together with previous findings, we discuss
      predictions on the spatio-temporal organization of precisely coordinated spiking
      on the mesoscopic scale as a function of beta power.

PMID- 29581431
TI  - Urban and nomadic isotopic niches reveal dietary connectivities along Central
      Asia's Silk Roads.
AB  - The ancient 'Silk Roads' formed a vast network of trade and exchange that
      facilitated the movement of commodities and agricultural products across medieval
      Central Asia via settled urban communities and mobile pastoralists. Considering
      food consumption patterns as an expression of socio-economic interaction, we
      analyse human remains for carbon and nitrogen isotopes in order to establish
      dietary intake, then model isotopic niches to characterize dietary diversity and
      infer connectivity among communities of urbanites and nomadic pastoralists. The
      combination of low isotopic variation visible within urban groups with isotopic
      distinction between urban communities irrespective of local environmental
      conditions strongly suggests localized food production systems provided primary
      subsistence rather than agricultural goods exchanged along trade routes. Nomadic
      communities, in contrast, experienced higher dietary diversity reflecting
      engagements with a wide assortment of foodstuffs typical for mobile communities.
      These data indicate tightly bound social connectivity in urban centres pointedly
      funnelled local food products and homogenized dietary intake within settled
      communities, whereas open and opportunistic systems of food production and
      circulation were possible through more mobile lifeways.

PMID- 29581432
TI  - Maternal deprivation induces alterations in cognitive and cortical function in
      adulthood.
AB  - Early life trauma is a risk factor for a number of neuropsychiatric disorders,
      including schizophrenia (SZ). The current study assessed how an early life
      traumatic event, maternal deprivation (MD), alters cognition and brain function
      in rodents. Rats were maternally deprived in the early postnatal period and then
      recognition memory (RM) was tested in adulthood using the novel object
      recognition task. The expression of catechol-o-methyl transferase (COMT) and
      glutamic acid decarboxylase (GAD67) were quantified in the medial prefrontal
      cortex (mPFC), ventral striatum, and temporal cortex (TC). In addition, depth EEG
      recordings were obtained from the mPFC, vertex, and TC during a paired-click
      paradigm to assess the effects of MD on sensory gating. MD animals exhibited
      impaired RM, lower expression of COMT in the mPFC and TC, and lower expression of
      GAD67 in the TC. Increased bioelectric noise was observed at each recording site
      of MD animals. MD animals also exhibited altered information theoretic measures
      of stimulus encoding. These data indicate that a neurodevelopmental perturbation
      yields persistent alterations in cognition and brain function, and are consistent
      with human studies that identified relationships between allelic differences in
      COMT and GAD67 and bioelectric noise. These changes evoked by MD also lead to
      alterations in shared information between cognitive and primary sensory
      processing areas, which provides insight into how early life trauma confers a
      risk for neurodevelopmental disorders, such as SZ, later in life.

PMID- 29581433
TI  - Silicon and glass very large scale microfluidic droplet integration for terascale
      generation of polymer microparticles.
AB  - Microfluidic chips can generate emulsions, which can be used to synthesize
      polymer microparticles that have superior pharmacological performance compared to
      particles prepared by conventional techniques. However, low production rates of
      microfluidics remains a challenge to successfully translate laboratory
      discoveries to commercial manufacturing. We present a silicon and glass device
      that incorporates an array of 10,260 (285 * 36) microfluidic droplet generators
      that uses only a single set of inlets and outlets, increasing throughput by
      >10,000* compared to microfluidics with a single generator. Our design breaks the
      tradeoff between the number of generators and the maximum throughput of
      individual generators by incorporating high aspect ratio flow resistors. We test
      these design strategies by generating hexadecane microdroplets at >1 trillion
      droplets per h with a coefficient of variation CV <3%. To demonstrate the
      synthesis of biocompatible microparticles, we generated 8-16 um polycaprolactone
      particles with a CV <5% at a rate of 277 g h-1.

PMID- 29581434
TI  - Organic osmolytes preserve the function of the developing tight junction in
      ultraviolet B-irradiated rat epidermal keratinocytes.
AB  - Epidermal barrier function is provided by the highly keratinised stratum corneum
      and also by tight junctions (TJs) in the granular layer of skin. The development
      of the TJ barrier significantly deteriorates in response to ultraviolet B
      radiation (UVB). Following exposure to UVB, keratinocytes accumulate organic
      osmolytes, which are known to preserve cell volume during water stress. Since TJs
      are intimately associated with control of water homeostasis in skin, we
      hypothesised that there may be a direct influence of osmolytes on TJ development.
      Exposure of rat epidermal keratinocytes (REKs) to a single dose of UVB reduced
      the function of developing TJs. This was concomitant with dislocalisation of
      claudin-1 and claudin-4 from the keratinocyte plasma membrane, phosphorylation of
      occludin and elevation of reactive oxygen species (ROS). In the presence of
      organic osmolytes, these effects were negated but were independent of the effects
      of these molecules on cell volume, elevation of ROS or the gene expression of TJ
      proteins. These data suggest that organic osmolytes affect TJs via post
      translational mechanism(s) possibly involving protection of the native
      conformation of TJ proteins.

PMID- 29581435
TI  - Correlation of Xpert MTB/RIF with measures to assess Mycobacterium tuberculosis
      bacillary burden in high HIV burden areas of Southern Africa.
AB  - Traditionally, smear microscopy has been used as a point-of-care measure of
      bacillary burden in tuberculosis patients to inform infection control and contact
      tracing. Xpert MTB/RIF has the potential to replace smear. However, data to
      support the use of its quantitative output [cycle threshold (CT)] as an alternate
      point-of-care measure of bacillary burden are limited. This study assessed the
      correlation (Spearman's) between CT, smear, culture time-to-positivity (TTP), and
      clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238)
      and South Africa (n = 462). Mean CT and smear grade correlated well (rho0.72);
      compared to TTP and smear (rho0.61); and mean CT and TTP (rho0.50). In
      multivariate analyses, lower CT (higher bacillary load) was associated with
      negative HIV serostatus and low BMI. A smear positivity rule-out (95%
      sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07
      positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly
      classified. Cut-offs were higher for HIV positive compared to HIV negative
      individuals for any set sensitivity level. This study suggests Xpert CT values
      correlate well with smear, both in HIV positive and negative individuals, and
      that CT cut-offs might be broadly applicable to multiple settings. Studies to
      directly assess the association of CT with infectiousness are needed.

PMID- 29581436
TI  - A highly efficient Cu(In,Ga)(S,Se)2 photocathode without a hetero-materials
      overlayer for solar-hydrogen production.
AB  - Surface modification of a Cu(In,Ga)(S,Se)2 (CIGSSe) absorber layer is commonly
      required to obtain high performance CIGSSe photocathodes. However, surface
      modifications can cause disadvantages such as optical loss, low stability, the
      use of toxic substances and an increase in complexity. In this work, we
      demonstrate that a double-graded bandgap structure (top-high, middle-low and
      bottom-high bandgaps) can achieve high performance in bare CIGSSe photocathodes
      without any surface modifications via a hetero-materials overlayer that have been
      fabricated in a cost-effective solution process. We used two kinds of CIGSSe film
      produced by different precursor solutions consisting of different solvents and
      binder materials, and both revealed a double-graded bandgap structure composed of
      an S-rich top layer, Ga- and S-poor middle layer and S- and Ga-rich bottom layer.
      The bare CIGSSe photocathode without surface modification exhibited a high
      photoelectrochemical activity of ~6 mA.cm-2 at 0 V vs. RHE and ~22 mA.cm-2 at 
      0.27 V vs. RHE, depending on the solution properties used in the CIGSSe film
      preparation. The incorporation of a Pt catalyst was found to further increase
      their PEC activity to ~26 mA.cm-2 at -0.16 V vs. RHE.

PMID- 29581437
TI  - Orthogonality of Pyrrolysine tRNA in the Xenopus oocyte.
AB  - Chemical aminoacylation of orthogonal tRNA allows for the genetic encoding of a
      wide range of synthetic amino acids without the need to evolve specific aminoacyl
      tRNA synthetases. This method, when paired with protein expression in the Xenopus
      laevis oocyte expression system, can extract atomic scale functional data from a
      protein structure to advance the study of membrane proteins. The utility of the
      method depends on the orthogonality of the tRNA species used to deliver the amino
      acid. Here, we report that the pyrrolysyl tRNA (pylT) from Methanosarcina barkeri
      fusaro is orthogonal and highly competent for genetic code expansion experiments
      in the Xenopus oocyte. The data show that pylT is amendable to chemical acylation
      in vitro; it is then used to rescue a cytoplasmic site within a voltage-gated
      sodium channel. Further, the high fidelity of the pylT is demonstrated via
      encoding of lysine within the selectivity filter of the sodium channel, where
      sodium ion recognition by the distal amine of this side-chain is essential. Thus,
      pylT is an appropriate tRNA species for delivery of amino acids via nonsense
      suppression in the Xenopus oocyte. It may prove useful in experimental contexts
      wherein reacylation of suppressor tRNAs have been observed.

PMID- 29581438
TI  - Structural modelling of the DNAJB6 oligomeric chaperone shows a peptide-binding
      cleft lined with conserved S/T-residues at the dimer interface.
AB  - The remarkably efficient suppression of amyloid fibril formation by the DNAJB6
      chaperone is dependent on a set of conserved S/T-residues and an oligomeric
      structure, features unusual among DNAJ chaperones. We explored the structure of
      DNAJB6 using a combination of structural methods. Lysine-specific crosslinking
      mass spectrometry provided distance constraints to select a homology model of the
      DNAJB6 monomer, which was subsequently used in crosslink-assisted docking to
      generate a dimer model. A peptide-binding cleft lined with S/T-residues is formed
      at the monomer-monomer interface. Mixed isotope crosslinking showed that the
      oligomers are dynamic entities that exchange subunits. The purified protein is
      well folded, soluble and composed of oligomers with a varying number of subunits
      according to small-angle X-ray scattering (SAXS). Elongated particles (160 * 120
      A) were detected by electron microscopy and single particle reconstruction
      resulted in a density map of 20 A resolution into which the DNAJB6 dimers fit.
      The structure of the oligomer and the S/T-rich region is of great importance for
      the understanding of the function of DNAJB6 and how it can bind aggregation-prone
      peptides and prevent amyloid diseases.

PMID- 29581439
TI  - A micro-CT-based method for quantitative brain lesion characterization and
      electrode localization.
AB  - Lesion verification and quantification is traditionally done via histological
      examination of sectioned brains, a time-consuming process that relies heavily on
      manual estimation. Such methods are particularly problematic in posterior
      cortical regions (e.g. visual cortex), where sectioning leads to significant
      damage and distortion of tissue. Even more challenging is the post hoc
      localization of micro-electrodes, which relies on the same techniques, suffers
      from similar drawbacks and requires even higher precision. Here, we propose a
      new, simple method for quantitative lesion characterization and electrode
      localization that is less labor-intensive and yields more detailed results than
      conventional methods. We leverage staining techniques standard in electron
      microscopy with the use of commodity micro-CT imaging. We stain whole rat and
      zebra finch brains in osmium tetroxide, embed these in resin and scan entire
      brains in a micro-CT machine. The scans result in 3D reconstructions of the
      brains with section thickness dependent on sample size (12-15 and 5-6 microns for
      rat and zebra finch respectively) that can be segmented manually or
      automatically. Because the method captures the entire intact brain volume,
      comparisons within and across studies are more tractable, and the extent of
      lesions and electrodes may be studied with higher accuracy than with current
      methods.

PMID- 29581440
TI  - Three-dimensional Epigenome Statistical Model: Genome-wide Chromatin Looping
      Prediction.
AB  - This study aims to understand through statistical learning the basic biophysical
      mechanisms behind three-dimensional folding of epigenomes. The 3DEpiLoop
      algorithm predicts three-dimensional chromatin looping interactions within
      topologically associating domains (TADs) from one-dimensional epigenomics and
      transcription factor profiles using the statistical learning. The predictions
      obtained by 3DEpiLoop are highly consistent with the reported experimental
      interactions. The complex signatures of epigenomic and transcription factors
      within the physically interacting chromatin regions (anchors) are similar across
      all genomic scales: genomic domains, chromosomal territories, cell types, and
      different individuals. We report the most important epigenetic and transcription
      factor features used for interaction identification either shared, or unique for
      each of sixteen (16) cell lines. The analysis shows that CTCF interaction anchors
      are enriched by transcription factors yet deficient in histone modifications,
      while the opposite is true in the case of RNAP II mediated interactions. The code
      is available at the repository https://bitbucket.org/4dnucleome/3depiloop .

PMID- 29581441
TI  - Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic
      Resonance Spectroscopy of Histologically Benign Tissue.
AB  - Prostate cancer alters cellular metabolism through events potentially preceding
      cancer morphological formation. Magnetic resonance spectroscopy (MRS)-based
      metabolomics of histologically-benign tissues from cancerous prostates can
      predict disease aggressiveness, offering clinically-translatable prognostic
      information. This retrospective study of 185 patients (2002-2009) included
      prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia
      (BPH) (n = 15), and biopsy cores from cancer-negative patients (n = 14). Tissues
      were measured with high resolution magic angle spinning (HRMAS) MRS, followed by
      quantitative histology using the Prognostic Grade Group (PGG) system. Metabolic
      profiles, measured solely from 338 of 365 histologically-benign tissues from
      cancerous prostates and divided into training-testing cohorts, could identify
      tumor grade and stage, and predict recurrence. Specifically, metabolic profiles:
      (1) show elevated myo-inositol, an endogenous tumor suppressor and potential
      mechanistic therapy target, in patients with highly-aggressive cancer, (2)
      identify a patient sub-group with less aggressive prostate cancer to avoid
      overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically
      indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby
      identifying patients more at-risk for recurrence. Such findings, achievable by
      biopsy or prostatectomy tissue measurement, could inform treatment strategies.
      Metabolomics information can help transform a morphology-based diagnostic system
      by invoking cancer biology to improve evaluation of histologically-benign tissues
      in cancer environments.

PMID- 29581443
TI  - The electromagnetic wave energy effect(s) in microwave-assisted organic syntheses
      (MAOS).
AB  - Organic reactions driven by microwaves have been subjected for several years to
      some enigmatic phenomenon referred to as the microwave effect, an effect often
      mentioned in microwave chemistry but seldom understood. We identify this
      microwave effect as an electromagnetic wave effect that influences many chemical
      reactions. In this article, we demonstrate its existence using three different
      types of microwave generators with dissimilar oscillation characteristics. We
      show that this effect is operative in photocatalyzed TiO2 reactions; it
      negatively influences electro-conductive catalyzed reactions, and yet has but a
      negligible effect on organic syntheses. The relationship between this
      electromagnetic wave effect and chemical reactions is elucidated from such
      energetic considerations as the photon energy and the reactions' activation
      energies.

PMID- 29581442
TI  - A vaccinia-based single vector construct multi-pathogen vaccine protects against
      both Zika and chikungunya viruses.
AB  - Zika and chikungunya viruses have caused major epidemics and are transmitted by
      Aedes aegypti and/or Aedes albopictus mosquitoes. The "Sementis Copenhagen
      Vector" (SCV) system is a recently developed vaccinia-based, multiplication
      defective, vaccine vector technology that allows manufacture in modified CHO
      cells. Herein we describe a single-vector construct SCV vaccine that encodes the
      structural polyprotein cassettes of both Zika and chikungunya viruses from
      different loci. A single vaccination of mice induces neutralizing antibodies to
      both viruses in wild-type and IFNAR-/- mice and protects against (i) chikungunya
      virus viremia and arthritis in wild-type mice, (ii) Zika virus viremia and
      fetal/placental infection in female IFNAR-/- mice, and (iii) Zika virus viremia
      and testes infection and pathology in male IFNAR-/- mice. To our knowledge this
      represents the first single-vector construct, multi-pathogen vaccine encoding
      large polyproteins, and offers both simplified manufacturing and formulation, and
      reduced "shot burden" for these often co-circulating arboviruses.

PMID- 29581444
TI  - Whole Genome Resequencing of Capsicum baccatum and Capsicum annuum to Discover
      Single Nucleotide Polymorphism Related to Powdery Mildew Resistance.
AB  - The present study deals with genome wide identification of single-nucleotide
      polymorphism (SNP) markers related to powdery mildew (PM) resistance in two
      pepper varieties. Capsicum baccatum (PRH1- a PM resistant line) and Capsicum
      annuum (Saengryeg- a PM susceptible line), were resequenced to develop SNP
      markers. A total of 6,213,009 and 6,840,889 SNPs for PRH1 and Saengryeg
      respectively have been discovered. Among the SNPs, majority were classified as
      homozygous type SNPs, particularly in the resistant line. Moreover, the SNPs were
      differentially distributed among the chromosomes in both the resistant and
      susceptible lines. In total, 4,887,031 polymorphic SNP loci were identified
      between the two lines and 306,871 high-resolution melting (HRM) marker primer
      sets were designed. In order to understand the SNPs associated with the vital
      genes involved in diseases resistance and stress associated processes, chromosome
      wise gene ontology analysis was performed. The results revealed the occurrence
      that SNPs related to diseases resistance genes were predominantly distributed in
      chromosome 4. In addition, 6281 SNPs associated with 46 resistance genes were
      identified. Among the lines, PRH1 consisted of maximum number of polymorphic SNPs
      related to NBS-LRR genes. The SNP markers were validated using HRM assay in 45 F4
      populations and correlated with the phenotypic disease index.

PMID- 29581445
TI  - Incongruent pitch cues are associated with increased activation and functional
      connectivity in the frontal areas.
AB  - Pitch plays a crucial role in music and speech perception. Pitch perception is
      characterized by multiple perceptual dimensions, such as pitch height and chroma.
      Information provided by auditory signals that are related to these perceptual
      dimensions can be either congruent or incongruent. To create conflicting cues for
      pitch perception, we modified Shepard tones by varying the pitch height and pitch
      chroma dimensions in either the same or opposite directions. Our behavioral data
      showed that most listeners judged pitch changes based on pitch chroma, instead of
      pitch height, when incongruent information was provided. The reliance on pitch
      chroma resulted in a stable percept of upward or downward pitch shift, rather
      than alternating between two different percepts. Across the incongruent and
      congruent conditions, consistent activation was found in the bilateral superior
      temporal and inferior frontal areas. In addition, significantly stronger
      activation was observed in the inferior frontal areas during the incongruent
      compared to congruent conditions. Enhanced functional connectivity was found
      between the left temporal and bilateral frontal areas in the incongruent than
      congruent conditions. Increased intra-hemispheric and inter-hemispheric
      connectivity was also observed in the frontal areas. Our results suggest the
      involvement of the frontal lobe in top-down and bottom-up processes to generate a
      stable percept of pitch change with conflicting perceptual cues.

PMID- 29581446
TI  - Propensity Score-Matched Analysis on the Association Between Pregnancy Infections
      and Adverse Birth Outcomes in Rural Northwestern China.
AB  - The purpose of this study is to examine the relationship between infections and
      birth outcomes in pregnant Chinese women by using propensity score (PS) matching.
      The data used here was from a large population-based cross-sectional
      epidemiological survey on birth defects in Shaanxi province, Northwest China. The
      babies born during 2010-2013 and their mothers were selected with a stratified
      multistage sampling method. We used PS-matched (1:1) analysis to match
      participants with infections to participants without infections. Of 22916 rural
      participants, the overall prevalence of infection was about 39.96%. 5381 pairs
      were matched. We observed increased risks of birth defects with infections,
      respiratory infections and genitourinary infections during the pregnancy (OR,
      1.59; 95% CI: 1.21-2.08; OR, 1.44; 95% CI: 1.10-1.87; OR, 3.11; 95% CI: 1.75
      5.54). There was also a significant increase of low birth weight associated with
      respiratory infections (1.13(1.01-1.27)). The association of birth defect with
      the infection could be relatively stable but the effect could be mediated by some
      important factors such as mother's age, education level and economic level. The
      infection during pregnancy is common in Chinese women and might increase the risk
      of offspring birth defects and low birth weight, especially in younger, lower
      education, poor pregnant women.

PMID- 29581447
TI  - Asymmetries in Distractibility: Left Distractors Improve Reaction Time
      Performance.
AB  - Research using the irrelevant-distractor paradigm shows perceptual load
      influences distractibility, such that distractors are more likely to be processed
      and decrease reaction times during low perceptual load. In contrast, under high
      load, attentional resources are limited, and the likelihood of distractibility is
      decreased. We manipulated distractor placement to determine whether location
      differentially influenced distractibility. During low load, reaction times were
      increased equally for all distractor locations. Under high load, left distractors
      speeded reaction times significantly more than right distractors. We suggest two
      potential explanations: (1) the central focus of attention was sufficiently large
      to encapsulate both the distractor and the visual array during low perceptual
      load, leading to increased distraction-during high load, attention was split
      across the two visual stimuli, allowing the distractors and array to be processed
      independently; (2) superior executive control for stimuli in the left visual
      field allowed participants to 'catch and release' left distractors more
      efficiently, ultimately decreasing distraction and providing a performance
      benefit. Our findings represent an intriguing development in relation to visual
      asymmetries in distractibility.

PMID- 29581448
TI  - Sulfate alters aerosol absorption properties in East Asian outflow.
AB  - Black carbon (BC) and brown carbon (BrC) aerosols that are released from the
      combustion of fossil fuels and biomass are of great concern because of their
      light-absorbing ability and great abundance associated with various anthropogenic
      sources, particularly in East Asia. However, the optical properties of ambient
      aerosols are dependent on the mixing state and the chemical composition of
      absorbing and non-absorbing aerosols. Here we examined how, in East Asian
      outflows, the parameters of the aerosol optical properties can be altered
      seasonally in conjunction with the mixing state and the chemical composition of
      aerosols, using 3-year aerosol measurements. Our findings highlight the important
      role played by sulfate in East Asia during the warm season in both enhancing
      single scattering albedo (SSA) and altering the absorption properties of aerosols
      enhancing mass absorption cross section of BC (MACBC) and reducing MAC of BrC
      (MACBrC,370). Therefore we suggest that in global radiative forcing models,
      particular attention should be paid to the consideration of the accurate
      treatment of the SO2 emission changes in the coming years in this region that
      will result from China's air quality policy.

PMID- 29581449
TI  - Adipose mesenchymal stem cells from osteoporotic donors preserve functionality
      and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy.
AB  - Maintenance of bone homeostasis against diseased microenvironments remains as a
      major challenge. Recently, mesenchymal stem cells (MSCs) have been unravelled as
      potent microenvironmental modulators, the systemic infusion of which in
      cytotherapy can prevent or rescue extensive bone loss via anti-inflammation.
      However, MSCs also accept microenvironmental regulations; particularly, MSCs from
      bone marrow (BMMSCs) are prone to pathological microenvironmental factors of
      bone. In this study, we discovered that BMMSCs from osteoporotic donors of
      ovariectomized (OVX) mice lost their anti-inflammatory capability and failed to
      prevent bone loss when infused back into OVX recipients. Nevertheless, MSCs from
      adipose tissues (ADMSCs) preserved their anti-inflammatory capacity, despite
      diseased microenvironments of OVX donors, and continued to show protective
      effects on bone in OVX recipients. In the cellular level, the anti-inflammatory
      superiority of osteoporotic donor-derived ADMSCs over BMMSCs existed in their
      distinctive capability to induce T-cell apoptosis, which was molecularly
      attributed to retained expression levels of critical immunomodulatory genes.
      Furthermore, these functional discrepancies of BMMSCs and ADMSCs were due to
      differential stemness, energy metabolism and anti-oxidative defence system,
      underlying general disparity in their cellular states. Collectively, our findings
      optimize osteoporotic cytotherapy by using ADMSCs in resistance to and in
      modulation of diseased microenvironments.

PMID- 29581450
TI  - Methylation-to-Expression Feature Models of Breast Cancer Accurately Predict
      Overall Survival, Distant-Recurrence Free Survival, and Pathologic Complete
      Response in Multiple Cohorts.
AB  - Prognostic biomarkers serve a variety of purposes in cancer treatment and
      research, such as prediction of cancer progression, and treatment eligibility.
      Despite growing interest in multi-omic data integration for defining prognostic
      biomarkers, validated methods have been slow to emerge. Given that breast cancer
      has been the focus of intense research, it is amenable to studying the benefits
      of multi-omic prognostic models due to the availability of datasets. Thus, we
      examined the efficacy of our methylation-to-expression feature model (M2EFM)
      approach to combining molecular and clinical predictors to create risk scores for
      overall survival, distant metastasis, and chemosensitivity in breast cancer. Gene
      expression, DNA methylation, and clinical variables were integrated via M2EFM to
      build models of overall survival using 1028 breast tumor samples and applied to
      validation cohorts of 61 and 327 samples. Models of distant recurrence-free
      survival and pathologic complete response were built using 306 samples and
      validated on 182 samples. Despite different populations and assays, M2EFM models
      validated with good accuracy (C-index or AUC >= 0.7) for all outcomes and had the
      most consistent performance compared to other methods. Finally, we demonstrated
      that M2EFM identifies functionally relevant genes, which could be useful in
      translating an M2EFM biomarker to the clinic.

PMID- 29581451
TI  - Modeling the effects of lipid peroxidation during ferroptosis on membrane
      properties.
AB  - Ferroptosis is a form of regulated cell death characterized by the accumulation
      of lipid hydroperoxides. There has been significant research on the pathways
      leading to the accumulation of oxidized lipids, but the downstream effects and
      how lipid peroxides cause cell death during ferroptosis remain a major puzzle. We
      evaluated key features of ferroptosis in newly developed molecular dynamics
      models of lipid membranes to investigate the biophysical consequences of lipid
      peroxidation, and generated hypotheses about how lipid peroxides contribute to
      cell death during ferroptosis.

PMID- 29581453
TI  - Extracting quasi-steady Lagrangian transport patterns from the ocean circulation:
      An application to the Gulf of Mexico.
AB  - We construct a climatology of Lagrangian coherent structures (LCSs)-the concealed
      skeleton that shapes transport-with a twelve-year-long data-assimilative
      simulation of the sea-surface circulation in the Gulf of Mexico (GoM). Computed
      as time-mean Cauchy-Green strain tensorlines of the climatological velocity, the
      climatological LCSs (cLCSs) unveil recurrent Lagrangian circulation patterns. The
      cLCSs strongly constrain the ensemble-mean Lagrangian circulation of the
      instantaneous model velocity, showing that a climatological velocity can preserve
      meaningful transport information. The quasi-steady transport patterns revealed by
      the cLCSs agree well with aspects of the GoM circulation described in several
      previous observational and numerical studies. For example, the cLCSs identify
      regions of persistent isolation, and suggest that coastal regions previously
      identified as high-risk for pollution impact are regions of maximal attraction.
      We also show that cLCSs are remarkably accurate at identifying transport patterns
      observed during the Deepwater Horizon and Ixtoc oil spills, and during the Grand
      LAgrangian Deployment (GLAD) experiment. Thus it is shown that computing cLCSs is
      an efficient and meaningful way of synthesizing vast amounts of Lagrangian
      information. The cLCS method confirms previous GoM studies, and contributes to
      our understanding by revealing the persistent nature of the dynamics and
      kinematics treated therein.

PMID- 29581452
TI  - Semi-Automated Biomarker Discovery from Pharmacodynamic Effects on EEG in ADHD
      Rodent Models.
AB  - We propose a novel semi-automatic approach to design biomarkers for capturing
      pharmacodynamic effects induced by pharmacological agents on the spectral power
      of electroencephalography (EEG) recordings. We apply this methodology to
      investigate the pharmacodynamic effects of methylphenidate (MPH) and atomoxetine
      (ATX) on attention deficit/hyperactivity disorder (ADHD), using rodent models. We
      inject the two agents into the spontaneously hypertensive rat (SHR) model of
      ADHD, the Wistar-Kyoto rat (WKY), and the Wistar rat (WIS), and record their EEG
      patterns. To assess individual EEG patterns quantitatively, we use an integrated
      methodological approach, which consists of calculating the mean, slope and
      intercept parameters of temporal records of EEG spectral power using a smoothing
      filter, outlier truncation, and linear regression. We apply Fisher discriminant
      analysis (FDA) to identify dominant discriminants to be heuristically
      consolidated into several new composite biomarkers. Results of the analysis of
      variance (ANOVA) and t-test show benefits in pharmacodynamic parameters,
      especially the slope parameter. Composite biomarker evaluation confirms their
      validity for genetic model stratification and the effects of the pharmacological
      agents used. The methodology proposed is of generic use as an approach to
      investigating thoroughly the dynamics of the EEG spectral power.

PMID- 29581454
TI  - Resonance interaction energy between two entangled atoms in a photonic bandgap
      environment.
AB  - We consider the resonance interaction energy between two identical entangled
      atoms, where one is in the excited state and the other in the ground state. They
      interact with the quantum electromagnetic field in the vacuum state and are
      placed in a photonic-bandgap environment with a dispersion relation quadratic
      near the gap edge and linear for low frequencies, while the atomic transition
      frequency is assumed to be inside the photonic gap and near its lower edge. This
      problem is strictly related to the coherent resonant energy transfer between
      atoms in external environments. The analysis involves both an isotropic three
      dimensional model and the one-dimensional case. The resonance interaction
      asymptotically decays faster with distance compared to the free-space case,
      specifically as 1/r2 compared to the 1/r free-space dependence in the three
      dimensional case, and as 1/r compared to the oscillatory dependence in free space
      for the one-dimensional case. Nonetheless, the interaction energy remains
      significant and much stronger than dispersion interactions between atoms. On the
      other hand, spontaneous emission is strongly suppressed by the environment and
      the correlated state is thus preserved by the spontaneous-decay decoherence
      effects. We conclude that our configuration is suitable for observing the elusive
      quantum resonance interaction between entangled atoms.

PMID- 29581455
TI  - Structural and Functional Connectivity Changes Beyond Visual Cortex in a Later
      Phase of Visual Perceptual Learning.
AB  - The neural mechanisms of visual perceptual learning (VPL) remain unclear.
      Previously we found that activation in the primary visual cortex (V1) increased
      in the early encoding phase of training, but returned to baseline levels in the
      later retention phase. To examine neural changes during the retention phase, we
      measured structural and functional connectivity changes using MRI. After weeks of
      training on a texture discrimination task, the fractional anisotropy of the
      inferior longitudinal fasciculus, a major tract connecting visual and anterior
      areas, was increased, as well as the functional connectivity between V1 and
      anterior regions mediated by the ILF. These changes were strongly correlated with
      behavioral performance improvements. These results suggest a two-phase model of
      VPL in which localized functional changes in V1 in the encoding phase of training
      are followed by changes in both structural and functional connectivity in ventral
      visual processing, perhaps leading to the long-term stabilization of VPL.

PMID- 29581456
TI  - Sex Genotyping of Archival Fixed and Immunolabeled Guinea Pig Cochleas.
AB  - For decades, outbred guinea pigs (GP) have been used as research models. Various
      past research studies using guinea pigs used measures that, unknown at the time,
      may be sex-dependent, but from which today, archival tissues may be all that
      remain. We aimed to provide a protocol for sex-typing archival guinea pig tissue,
      whereby past experiments could be re-evaluated for sex effects. No PCR sex
      genotyping protocols existed for GP. We found that published sequence of the GP
      Sry gene differed from that in two separate GP stocks. We used sequences from
      other species to deduce PCR primers for Sry. After developing a genomic DNA
      extraction for archival, fixed, decalcified, immunolabeled, guinea pig cochlear
      half-turns, we used a multiplex assay (Y-specific Sry; X-specific Dystrophin) to
      assign sex to tissue as old as 3 years. This procedure should allow reevaluation
      of prior guinea pig studies in various research areas for the effects of sex on
      experimental outcomes.

PMID- 29581457
TI  - Counterregulation of cAMP-directed kinase activities controls ciliogenesis.
AB  - The primary cilium emanates from the cell surface of growth-arrested cells and
      plays a central role in vertebrate development and tissue homeostasis. The
      mechanisms that control ciliogenesis have been extensively explored. However, the
      intersection between GPCR signaling and the ubiquitin pathway in the control of
      cilium stability are unknown. Here we observe that cAMP elevation promotes cilia
      resorption. At centriolar satellites, we identify a multimeric complex nucleated
      by PCM1 that includes two kinases, NEK10 and PKA, and the E3 ubiquitin ligase
      CHIP. We show that NEK10 is essential for ciliogenesis in mammals and for the
      development of medaka fish. PKA phosphorylation primes NEK10 for CHIP-mediated
      ubiquitination and proteolysis resulting in cilia resorption. Disarrangement of
      this control mechanism occurs in proliferative and genetic disorders. These
      findings unveil a pericentriolar kinase signalosome that efficiently links the
      cAMP cascade with the ubiquitin-proteasome system, thereby controlling essential
      aspects of ciliogenesis.

PMID- 29581458
TI  - Application of Quantitative Microstructural MR Imaging with Atlas-based Analysis
      for the Spinal Cord in Cervical Spondylotic Myelopathy.
AB  - Mapping of MR fiber g-ratio, which is the ratio of the diameter of the axon to
      the diameter of the neuronal fiber, is introduced in this article. We
      investigated the MR fiber g-ratio, the axon volume fraction (AVF) and the myelin
      volume fraction (MVF) to evaluate microstructural changes in the spinal cord in
      patients with cervical spondylotic myelopathy (CSM) in vivo, using atlas-based
      analysis. We used diffusion MRI data acquired with a new simultaneous multi-slice
      accelerated readout-segmented echo planar imaging sequence for diffusion analysis
      for AVF calculation and magnetization transfer saturation imaging for MVF
      calculation. The AVFs of fasciculus gracilis in the affected side spinal cord,
      fasciculus cuneatus and lateral corticospinal tracts (LSCT) in the affected and
      unaffected side spinal cord were significantly lower (P = 0.019, 0.001, 0019,
      0.000, and 0.002, respectively) than those of normal controls. No difference was
      found in the MVFs. The fiber g-ratio of LSCT was significantly lower (P = 0.040)
      in the affected side spinal cords than in the normal controls. The pathological
      microstructural changes in the spinal cord in patients with CSM, presumably
      partial axonal degenerations with preserved myelin. This technique has the
      potential to be a clinical biomarker in patients with CSM in vivo.

PMID- 29581459
TI  - Predictors and estimation of risk for early exit from working life by poor health
      among middle and older aged workers in Korea.
AB  - The aims of this study were to investigate the predictors and estimate the risk
      for early exit from work owing to poor personal health status of the retirees.
      This study analysed the longitudinal data of 2,708 workers aged more than 45
      years old from the Korean Longitudinal Study of Ageing. Multivariate Cox
      regression analyses were conducted to identify the predictors and to build a
      prediction model for early exit from work due to poor health. Internal validation
      was performed using random split, and external validation using the English
      Longitudinal Study of Ageing. Over the 8-year follow-up, 124 workers exited work
      early because of poor health. Significant predictors for early exit from work due
      to poor health included hypertension (hazard ratio [HR], 1.52; 95% confidence
      interval [CI], 1.01-2.28), abnormal body mass index (HR, 1.60; 95% CI, 1.10
      2.35), decreased grasping power index, and perceived health status. The
      prediction model designed to estimate the risk of unwanted early exit from work
      because of poor health status showed fair performance in both the internal and
      external validations. The current study revealed the specific determinants and
      the possibility of prediction of shortened working life due to poor health
      status.

PMID- 29581460
TI  - Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/-
      Murine Incisors.
AB  - Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls,
      enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial
      cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem
      cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study,
      Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of
      polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased
      expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb
      knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell
      line presented a similar expression pattern. Therefore, the EMT enabled
      disengaged odontogenic epithelial stem cells to develop supernumerary teeth.
      Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin
      expression, and Decorin-positive staining in the periapical region, indicating
      their involvement in supernumerary tooth formation. Cebpb and Runx2 acted
      synergistically and played an important role in the formation of supernumerary
      teeth in adult incisors.

PMID- 29581461
TI  - Transcriptome-wide identification and screening of WRKY factors involved in the
      regulation of taxol biosynthesis in Taxus chinensis.
AB  - WRKY, a plant-specific transcription factor family, plays important roles in
      pathogen defense, abiotic cues, phytohormone signaling, and regulation of plant
      secondary metabolism. However, little is known about the roles, functions, and
      mechanisms of WRKY in taxane biosynthesis in Taxus spp. In this study, 61
      transcripts were identified from Taxus chinensis transcriptome datasets by using
      hidden Markov model search. All of these transcripts encoded proteins containing
      WRKY domains, which were designated as TcWRKY1-61. After phylogenetic analysis of
      the WRKY domains of TcWRKYs and AtWRKYs, 16, 8, 10, 14, 5, 7, and 1 TcWRKYs were
      cladded into Group I, IIa-IIe, and III, respectively. Then, six representative
      TcWRKYs were selected to classify their effects on taxol biosynthesis. After MeJA
      (methyl jasmonate acid) and SA (salicylic acid) treatments, all of the six
      TcWRKYs were upregulated by MeJA treatment. TcWRKY44 (IId) and TcWRKY47 (IIa)
      were upregulated, whereas TcWRKY8 (IIc), TcWRKY20 (III), TcWRKY26 (I), TcWRKY41
      (IIe), and TcWRKY52 (IIb) were downregulated by SA treatment. Overexpression
      experiments showed that the six selected TcWRKYs exerted different effects on
      taxol biosynthesis. In specific, TcWRKY8 and TcWRKY47 significantly improved the
      expression levels of taxol-biosynthesis-related genes. Transcriptome-wide
      identification of WRKY factors in Taxus not only enhances our understanding of
      plant WRKY factors but also identifies candidate regulators of taxol
      biosynthesis.

PMID- 29581462
TI  - Persistent random deformation model of cells crawling on a gel surface.
AB  - In general, cells move on a substrate through extension and contraction of the
      cell body. Though cell movement should be explained by taking into account the
      effect of such shape fluctuations, past approaches to formulate cell-crawling
      have not sufficiently quantified the relationship between cell movement (velocity
      and trajectory) and shape fluctuations based on experimental data regarding
      actual shaping dynamics. To clarify this relationship, we experimentally
      characterized cell-crawling in terms of shape fluctuations, especially extension
      and contraction, by using an elasticity-tunable gel substrate to modulate cell
      shape. As a result, an amoeboid swimmer-like relation was found to arise between
      the cell velocity and cell-shape dynamics. To formulate this experimentally
      obtained relationship between cell movement and shaping dynamics, we established
      a persistent random deformation (PRD) model based on equations of a deformable
      self-propelled particle adopting an amoeboid swimmer-like velocity-shape
      relationship. The PRD model successfully explains the statistical properties of
      velocity, trajectory and shaping dynamics of the cells including back-and-forth
      motion, because the velocity equation exhibits time-reverse symmetry, which is
      essentially different from previous models. We discuss the possible application
      of this model to classify the phenotype of cell migration based on the
      characteristic relation between movement and shaping dynamics.

PMID- 29581463
TI  - Engineered 3D vascular and neuronal networks in a microfluidic platform.
AB  - Neurovascular coupling plays a key role in the pathogenesis of neurodegenerative
      disorders including motor neuron disease (MND). In vitro models provide an
      opportunity to understand the pathogenesis of MND, and offer the potential for
      drug screening. Here, we describe a new 3D microvascular and neuronal network
      model in a microfluidic platform to investigate interactions between these two
      systems. Both 3D networks were established by co-culturing human embryonic stem
      (ES)-derived MN spheroids and endothelial cells (ECs) in microfluidic devices. Co
      culture with ECs improves neurite elongation and neuronal connectivity as
      measured by Ca2+ oscillation. This improvement was regulated not only by
      paracrine signals such as brain-derived neurotrophic factor secreted by ECs but
      also through direct cell-cell interactions via the delta-notch pathway, promoting
      neuron differentiation and neuroprotection. Bi-directional signaling was observed
      in that the neural networks also affected vascular network formation under
      perfusion culture. This in vitro model could enable investigations of neuro
      vascular coupling, essential to understanding the pathogenesis of
      neurodegenerative diseases including MNDs such as amyotrophic lateral sclerosis.

PMID- 29581464
TI  - Whole-exome Sequencing Helps the Diagnosis and Treatment in Children with
      Neurodevelopmental Delay Accompanied Unexplained Dyspnea.
AB  - Neurodevelopmental delay accompanied unexplained dyspnea is a highly lethal
      disease in clinic. This study is to investigate the performance characteristics
      of trio whole exome sequencing (Trio-WES) in a pediatric setting by presenting
      our patient cohort and displaying the diagnostic yield. A total of 31 pediatric
      patients showing neurodevelopmental delay accompanied unexplained dyspnea were
      admitted to our hospital and referred for molecular genetic testing using Trio
      WES. Eight genes namely MMACHC, G6PC, G6PT, ETFDH, OTC, NDUFAF5, SLC22A5, and
      MAGEL2 were suspected to be responsible for the onset of the clinical symptoms
      and 6 variants were novel. Standard interpretation according to ACMG guideline
      showed that the variants were pathogenic. Finally, diagnosis of methylmalonic
      aciduria and homocystinuria, glycogen storage disease, ornithine transcarbamylase
      deficiency, glutaric acidemia II, mitochondrial complex 1 deficiency, carnitine
      deficiency, and Schaaf-Yang syndrome was made in 12 out of the 31 patients. Trio
      WES is an effective means for molecular diagnosis of infantile neurodevelopmental
      delay accompanied unexplained dyspnea. As for molecular etiology identification,
      when routine potential monogenetic inheritance patterns including de novo,
      autosomal recessive, autosomal dominant, and X-linked recessive inheritance
      analysis is negative, physicians should take into account imprinted genes.

PMID- 29581465
TI  - Dietary genistein supplementation for breeders and their offspring improves the
      growth performance and immune function of broilers.
AB  - Genistein (GEN) is mainly extracted from soy plants and has potential functions
      as an antioxidant and in promoting immune function and growth. This study
      evaluated the effects of feeding breeders and their offspring dietary GEN on the
      immune function and growth performance of broiler chicks. Breeders were assigned
      to a control diet or GEN diet (control diet +400 mg/kg GEN), and their offspring
      were fed a control diet or GEN diet (control diet +40 mg/kg GEN). GEN treatment
      increased the body weight gain, tibial length, tibial width and slaughter
      performance of broilers and decreased the feed conversion ratio. The treatment
      also affected skeletal muscle myosin assembly and growth and increased growth
      hormone levels and IGF-I and IGFBP1 expression. Following GEN treatment, antigen
      processing and presentation, macrophage activation, B lymphocyte, NK cell and
      helper T cell proliferation, and CD4+ T lymphocyte differentiation all increased
      significantly. Increases were also observed in IgM and IgG concentrations,
      antibody titers, and antioxidant capacity. In addition, GEN treatment activated
      the Toll-like receptor signaling pathway and MAPK cascade signaling pathway. In
      summary, dietary GEN supplementation for breeders and their offspring can improve
      the growth performance and immune function of broiler chicks.

PMID- 29581466
TI  - A band of bound states in the continuum induced by disorder.
AB  - Bound states in the continuum usually refer to the phenomenon of a single or a
      few discrete bound states embedded in a continuous spectrum of extended states.
      Here we propose a simple mechanism to achieve a band of bound states in the
      continuum in a class of disordered quasi-1D and quasi-2D systems, where the bound
      states and extended states overlap completely in a spectral range. The systems
      are partially disordered in a way that a band of extended states always exists,
      not affected by the randomness, whereas the states in all other bands become
      localized and cover the entire spectrum of extended states. We demonstrate such
      disordered-induced bound states in the continuum in disordered multi-chain and
      multi-layer systems.

PMID- 29581467
TI  - Extracting biological age from biomedical data via deep learning: too much of a
      good thing?
AB  - Age-related physiological changes in humans are linearly associated with age.
      Naturally, linear combinations of physiological measures trained to estimate
      chronological age have recently emerged as a practical way to quantify aging in
      the form of biological age. In this work, we used one-week long physical activity
      records from a 2003-2006 National Health and Nutrition Examination Survey
      (NHANES) to compare three increasingly accurate biological age models: the
      unsupervised Principal Components Analysis (PCA) score, a multivariate linear
      regression, and a state-of-the-art deep convolutional neural network (CNN). We
      found that the supervised approaches produce better chronological age estimations
      at the expense of a loss of the association between the aging acceleration and
      all-cause mortality. Consequently, we turned to the NHANES death register
      directly and introduced a novel way to train parametric proportional hazards
      models suitable for out-of-the-box implementation with any modern machine
      learning software. As a demonstration, we produced a separate deep CNN for
      mortality risks prediction that outperformed any of the biological age or a
      simple linear proportional hazards model. Altogether, our findings demonstrate
      the emerging potential of combined wearable sensors and deep learning
      technologies for applications involving continuous health risk monitoring and
      real-time feedback to patients and care providers.

PMID- 29581469
TI  - Comparative transcriptomics gives insights into the evolution of parasitism in
      Strongyloides nematodes at the genus, subclade and species level.
AB  - Strongyloides spp., gastrointestinal nematode parasites of humans and other
      animals, have genetically identical parasitic and free-living adult life cycle
      stages. This is an almost unique feature amongst nematodes and comparison of
      these two stages can provide insights into the genetic basis and evolution of
      Strongyloides nematode parasitism. Here, we present RNAseq data for S.
      venezuelensis, a parasite of rodents, and identify genes that are differentially
      expressed in parasitic and free-living life cycle stages. Comparison of these
      data with analogous RNAseq data for three other Strongyloides spp., has
      identified key protein-coding gene families with a putative role in parasitism
      including WAGO-like Argonautes (at the genus level) and speckle-type POZ-like
      coding genes (S. venezuelensis-S. papillosus phylogenetic subclade level).
      Diverse gene families are uniquely upregulated in the parasitic stage of all four
      Strongyloides species, including a distinct upregulation of genes encoding
      cytochrome P450 in S. venezuelensis, suggesting some diversification of the
      molecular tools used in the parasitic life cycle stage among individual species.
      Together, our results identify key gene families with a putative role in
      Strongyloides parasitism or features of the parasitic life cycle stage, and
      deepen our understanding of parasitism evolution among Strongyloides species.

PMID- 29581468
TI  - Long term potentiation, but not depression, in interlamellar hippocampus CA1.
AB  - Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively
      studied while interlamellar CA1 to CA1 connections have not yet received much
      attention. One of our earlier studies demonstrated that axons of CA1 pyramidal
      neurons project to neighboring CA1 neurons, implicating information transfer
      along a longitudinal interlamellar network. Still, it remains unclear whether
      long-term synaptic plasticity is present within this longitudinal CA1 network.
      Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells,
      using in vitro and in vivo extracellular recordings and 3D holography glutamate
      uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long
      term potentiation (LTP) without direction or layer selectivity. By contrast, we
      find no significant long-term depression (LTD) under various LTD induction
      protocols. These results implicate unique synaptic properties in the longitudinal
      projection suggesting that the interlamellar CA1 network could be a promising
      structure for hippocampus-related information processing and brain diseases.

PMID- 29581470
TI  - Factors associated with cognitive impairment in elderly versus nonelderly
      patients with metabolic syndrome: the different roles of FGF21.
AB  - Increased fibroblast growth factor 21 (FGF21) levels have been found in patients
      with metabolic syndrome (MetS). MetS is also associated with cognitive decline.
      However, the correlation between FGF21 and cognitive decline in elderly and
      nonelderly MetS patients has not been investigated. 116 non-elderly patients (age
      <65 years old) and 96 elderly patients (>=65 years old) with MetS were enrolled.
      Blood samples for FGF21 were collected from all participants after 12-hour
      fasting. Cognitive function was assessed using the Montreal cognitive assessment
      (MoCA) test. The MoCA score was negatively associated with age and was different
      among different levels of education in these MetS patients. In the non-elderly
      group, body mass index (BMI) showed positively correlated with MoCA score while,
      FGF21 level and HbA1C were negatively associated with the MoCA score in non
      elderly MetS patients. BMI was the only factor which showed a negative
      correlation with the MoCA score in elderly MetS patients. This study demonstrated
      that FGF21 level was independently associated with cognitive impairment in non
      elderly patients but not in elderly patients. The possible role of FGF21 level in
      cognitive impairment in non-elderly should be confirmed in a prospective study.

PMID- 29581471
TI  - Using spatial mark-recapture for conservation monitoring of grizzly bear
      populations in Alberta.
AB  - One of the challenges in conservation is determining patterns and responses in
      population density and distribution as it relates to habitat and changes in
      anthropogenic activities. We applied spatially explicit capture recapture (SECR)
      methods, combined with density surface modelling from five grizzly bear (Ursus
      arctos) management areas (BMAs) in Alberta, Canada, to assess SECR methods and to
      explore factors influencing bear distribution. Here we used models of grizzly
      bear habitat and mortality risk to test local density associations using density
      surface modelling. Results demonstrated BMA-specific factors influenced density,
      as well as the effects of habitat and topography on detections and movements of
      bears. Estimates from SECR were similar to those from closed population models
      and telemetry data, but with similar or higher levels of precision. Habitat was
      most associated with areas of higher bear density in the north, whereas mortality
      risk was most associated (negatively) with density of bears in the south.
      Comparisons of the distribution of mortality risk and habitat revealed
      differences by BMA that in turn influenced local abundance of bears. Combining
      SECR methods with density surface modelling increases the resolution of mark
      recapture methods by directly inferring the effect of spatial factors on
      regulating local densities of animals.

PMID- 29581472
TI  - Proteomic analysis of plasma extracellular vesicles reveals mitochondrial stress
      upon HTLV-1 infection.
AB  - Extracellular vesicles (EVs) can participate in intercellular communication and
      pathogenesis. EVs contain many cargos, including proteins, and the composition of
      EVs differs between cell-types and activation levels. Thus, plasma EVs can be
      used as a biomarker of systemic response to infection and/or disease progression.
      In this study, we aimed at describing alterations in the protein content of
      plasma EVs upon infection with the human T-lymphotropic retrovirus type 1 (HTLV
      1). HTLV-1 is the etiological agent of a lymphoproliferative disease (ATL) and a
      series of inflammatory diseases, including a neurodegenerative inflammatory
      disease (HAM/TSP). We found that plasma EVs are more abundant and smaller in HTLV
      1 asymptomatic carriers or HAM/TSP patients when compared to uninfected healthy
      donors. Moreover, EVs from HTLV-1 infected donors contain markers of metabolic
      and mitochondrial stress.

PMID- 29581473
TI  - Revealing Individual Lifestyles through Mass Spectrometry Imaging of Chemical
      Compounds in Fingerprints.
AB  - Fingerprints, specifically the ridge details within the print, have long been
      used in forensic investigations for individual identification. Beyond the ridge
      detail, fingerprints contain useful chemical information. The study of
      fingerprint chemical information has become of interest, especially with mass
      spectrometry imaging technologies. Mass spectrometry imaging visualizes the
      spatial relationship of each compound detected, allowing ridge detail and
      chemical information in a single analysis. In this work, a range of exogenous
      fingerprint compounds that may reveal a personal lifestyle were studied using
      matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI
      MSI). Studied chemical compounds include various brands of bug sprays and
      sunscreens, as well as food oils, alcohols, and citrus fruits. Brand
      differentiation and source determination were possible based on the active
      ingredients or exclusive compounds left in fingerprints. Tandem mass spectrometry
      was performed for the key compounds, so that these compounds could be confidently
      identified in a single multiplex mass spectrometry imaging data acquisition.

PMID- 29581474
TI  - Furin inhibitor protects against neuronal cell death induced by activated NMDA
      receptors.
AB  - The proprotein convertases (PCs) act as serine proteases and are known to convert
      diverse precursor proteins into their active forms. Among the PCs, furin has been
      considered to play a crucial role not only in embryogenesis, but also in the
      initiation and progression of certain pathologic conditions. However, the roles
      played by furin with respect to neuronal cell injuries remain to be determined.
      An excessive influx of Ca2+ through the N-methyl-d-aspartate (NMDA) receptor has
      been associated with diverse neurological and neurodegenerative disorders. The
      aim of this study was to achieve further insight into the pathophysiologic roles
      of furin in cultured cortical neurons. We demonstrated that furin inhibitors dose
      dependently prevented neuronal injury induced by NMDA treatment. Neuronal injury
      induced by NMDA treatment was attenuated by the calpain inhibitor calpeptin. And
      the increase observed in the activity of calpain after NMDA treatment was
      significantly inhibited by these furin inhibitors. Furthermore, calpain-2
      activity, which was evaluated by means of the immunoblotting assay, was increased
      by NMDA treatment. It was noteworthy that this increased activity was almost
      completely inhibited by a furin inhibitor. Our findings suggested that furin is
      involved in NMDA-induced neuronal injury by acting upstream of calpain.

PMID- 29581475
TI  - Tuning the 0 - pi Josephson junction with a magnetic impurity: Role of tunnel
      contacts, exchange coupling, e - e interactions and high-spin states.
AB  - We propose Josephson junction with a high-spin magnetic impurity sandwiched
      between two superconductors. This system shows a pi junction behavior as a
      function of the spin magnetic moment state of the impurity, the interface
      transparency, exchange coupling and electron-electron interactions in the system.
      The system is theoretically analyzed for possible reason behind the pi shift. The
      crucial role of spin flip scattering is highlighted. Possible applications in
      quantum computation of our proposed tunable high spin magnetic impurity pi
      junction is underscored.

PMID- 29581476
TI  - Dynamic Evolution of alpha-Gliadin Prolamin Gene Family in Homeologous Genomes of
      Hexaploid Wheat.
AB  - Wheat Gli-2 loci encode complex groups of alpha-gliadin prolamins that are
      important for breadmaking, but also major triggers of celiac disease (CD).
      Elucidation of alpha-gliadin evolution provides knowledge to produce wheat with
      better end-use properties and reduced immunogenic potential. The Gli-2 loci
      contain a large number of tandemly duplicated genes and highly repetitive DNA,
      making sequence assembly of their genomic regions challenging. Here, we
      constructed high-quality sequences spanning the three wheat homeologous alpha
      gliadin loci by aligning PacBio-based sequence contigs with BioNano genome maps.
      A total of 47 alpha-gliadin genes were identified with only 26 encoding intact
      full-length protein products. Analyses of alpha-gliadin loci and phylogenetic
      tree reconstruction indicate significant duplications of alpha-gliadin genes in
      the last ~2.5 million years after the divergence of the A, B and D genomes,
      supporting its rapid lineage-independent expansion in different Triticeae
      genomes. We showed that dramatic divergence in expression of alpha-gliadin genes
      could not be attributed to sequence variations in the promoter regions. The study
      also provided insights into the evolution of CD epitopes and identified a single
      indel event in the hexaploid wheat D genome that likely resulted in the
      generation of the highly toxic 33-mer CD epitope.

PMID- 29581477
TI  - Metal behavior in the extremes of dynamics.
AB  - When the rate of loading is faster than the rate at which material absorbs and
      converts energy to plastic work and damages, then there is an excess of energy
      that is partly stored in the material's microstructure and the rest of it
      triggers micro-dynamic excitations. The additional storage necessitates the
      development of plastic flow constraints and is directly responsible for the
      observed dynamic strengthening. At extreme conditions, we find that the micro
      excitations contribute to the dynamic behavior. The phenomena are universally
      observed in metals, frictional materials and polymers. In essence, strong
      dynamics creates conditions at which materials are pushed from equilibrium and
      temporarily reside in an excited state of behavior. This study is focused on the
      behavior of metals. The concept is incorporated into a mechanisms-based
      constitutive model and is examined for annealed OFHC copper.

PMID- 29581479
TI  - Effects of Structural and Energetic Disorders on Charge Transports in Crystal and
      Amorphous Organic Layers.
AB  - Understanding charge transports in organic films is important for both
      fundamental science and practical applications. Here, contributions of off
      diagonal (structural) and diagonal (energetic) disorders to charge transports
      were clarified using molecular-based multiscale simulation. These disorders,
      important for understanding charge transport in organic systems, are investigated
      by comparing crystal and amorphous aggregates of N,N'-diphenyl-N,N'-bis(1
      naphthyl)-1,1'-biphenyl-4,4'-diamine (NPD). Although NPD has been used as a hole
      transport material, it also exhibits comparable electron mobility experimentally.
      The experimental mobility and its electric field dependence in amorphous layers
      were reasonably reproduced by the multiscale simulation, confirming the electron
      transport properties of NPD. We assumed that the structural disorder would lower
      mobilities; however, the mobilities were found to be independent of the degree of
      structural disorder. Energetic disorder markedly lowered charge mobility instead.
      Charge migration in crystals was dominated by maximum electronic coupling pairs,
      whereas small electronic coupling pairs significantly contributed to charge
      transport in amorphous aggregate.

PMID- 29581478
TI  - Heparanase attenuates axon degeneration following sciatic nerve transection.
AB  - Axon degeneration underlies many nervous system diseases; therefore understanding
      the regulatory signalling pathways is fundamental to identifying potential
      therapeutics. Previously, we demonstrated heparan sulphates (HS) as a potentially
      new target for promoting CNS repair. HS modulate cell signalling by both acting
      as cofactors in the formation of ligand-receptor complexes and in sequestering
      ligands in the extracellular matrix. The enzyme heparanase (Hpse) negatively
      regulates these processes by cleaving HS and releasing the attached proteins,
      thereby attenuating their ligand-receptor interaction. To explore a comparative
      role for HS in PNS axon injury/repair we data mined published microarrays from
      distal sciatic nerve injury. We identified Hpse as a previously unexplored
      candidate, being up-regulated following injury. We confirmed these results and
      demonstrated inhibition of Hpse led to an acceleration of axonal degeneration,
      accompanied by an increase in beta-catenin. Inhibition of beta-catenin and the
      addition of Heparinase I both attenuated axonal degeneration. Furthermore the
      inhibition of Hpse positively regulates transcription of genes associated with
      peripheral neuropathies and Schwann cell de-differentiation. Thus, we propose
      Hpse participates in the regulation of the Schwann cell injury response and axo
      glia support, in part via the regulation of Schwann cell de-differentiation and
      is a potential therapeutic that warrants further investigation.

PMID- 29581480
TI  - Late cardiovascular morbidity and mortality following pediatric allogeneic
      hematopoietic cell transplantation.
AB  - We analyzed late cardiovascular outcomes of 661 patients who survived at least 2
      years from hematopoietic cell transplantation for childhood hematologic
      malignancy between 1995 and 2008. Center for International Blood and Marrow
      Transplant Research data was supplemented with surveys focused on cardiotoxicity
      and potential risk factors. The median duration of follow-up was 97 months (range
      24-230). 4.2% of survivors experienced at least one of the primary outcomes
      including coronary artery disease (0.2%), cerebrovascular accident (0.6%),
      cardiomyopathy (3%), and cardiac-related death (0.5%). Patients who received
      anthracycline chemotherapy (HR 4.67, p = 0.036) or cranial or chest radiation (HR
      5.58, p < 0.0001; HR 2.18, p = 0.0087) were at increased risk for developing one
      of the primary outcomes. Dyslipidemia was diagnosed in 18% of survivors. Pre
      transplant anthracycline (HR 1.74, p < 0.0001) and chest radiation (HR 1.34, p =
      0.0371) were risk factors for dyslipidemia. Overweight/obese body mass status was
      present in 63% of patients at baseline, 65% at 2 years, and 52% at most recent
      evaluation. Diabetes was diagnosed in 7% of subjects. In conclusion, severe
      cardiovascular complications were infrequently reported. The incidence of risk
      factors including obesity and dyslipidemia were significant and will likely
      increase the risk of cardiovascular disease over time in transplant survivors.

PMID- 29581481
TI  - Linked homozygous BMPR1B and PDHA2 variants in a consanguineous family with
      complex digit malformation and male infertility.
AB  - In affected members of a consanguineous family, a syndrome, which is concurrence
      of set of medical signs, is often observed and commonly assumed to have arisen
      from pleiotropy, i.e., the phenomenon of a single gene variant affecting multiple
      traits. We detected six sibs afflicted with a unique combination of digit
      malformation that includes brachydactyly, symphalangism and zygodactyly plus
      infertility in males owing to azoospermia, sperm immotility or necrospermia,
      which we hypothesised to have arisen from a defect in a single gene. We mapped
      the disease locus and by exome sequencing identified in patients homozygous
      missense variants bone morphogenetic protein receptor type IB (BMPR1B) c.640C>T
      (p.(Arg214Cys)) and alpha-2 pyruvate dehydrogenase (PDHA2) c.679A>G
      (p.(Met227Val)). Structural protein modelling, protein sequence conservation and
      in silico analysis indicate that both variants affect protein function. BMPR1B is
      known to be responsible for autosomal dominant brachydactyly and autosomal
      recessive acromesomelic chondrodysplasia. Our findings show that also recessive
      complex digit malformation can be caused by BMPR1B variant and not all biallelic
      BMPR1B variants cause acromesomelic dysplasia. PDHA2 is a novel candidate gene
      for male infertility; the protein product is a mitochondrial enzyme with highest
      expression in ejaculated sperm. Our findings are a unique example of two linked
      variants, ~ 711 Kb apart, in different genes that together manifest as a novel
      syndrome. They demonstrate that exome sequencing and not candidate gene approach
      should be employed in disease gene hunt, defining new diseases and genetic
      testing, to rule out the coincidental presence of two variants contributing
      together to the phenotype, which may be discerned as a novel disease.

PMID- 29581482
TI  - Higher High-Sensitivity C Reactive Protein is Associated with Future Premature
      Ventricular Contraction: a Community Based Prospective Cohort Study.
AB  - We aimed to determine whether hs-CRP is a predictor of future premature
      ventricular contraction (PVC) events in a community based population. A total of
      101,510 participants were recruited at baseline (2006-2007). The follow-up visits
      were conducted every two years. Participants who were free from PVC at baseline
      and achieved the fourth visit, or diagnosed of PVC during the subsequent visits
      were included for analyses. Diagnosis of PVC was based on standard supine
      resting, 10-s 12-lead ECG. Cox regression was applied to evaluate the association
      between quartiles of hs-CRP and the incidence of PVCs. 60710 participants (male:
      79.9%, mean age 49.4 years) were included for analyses. During a mean follow-up
      of 74.9 +/- 7.4 months, 908 (1.5%) participants were diagnosed with PVC.
      Participants of the highest quartile of hs-CRP had significantly increased risk
      of PVC events as compared with the lowest quartile (HR 1.36; 95% CI 1.12-1.66);
      and stratified analyses showed similar result in males (HR 1.45; 95% CI 1.16
      1.80), but not in females (HR 1.12; 95% CI 0.71-1.79). Moreover, elevated serum
      hs-CRP was associated with future PVC in participants without history of
      myocardial infarction or stroke (HR 1.34; 95% CI 1.09-1.65). Elevated hs-CRP was
      an independent predictor of PVC in Chinese population, especially in men.

PMID- 29581483
TI  - Height and overall cancer risk and mortality: evidence from a Mendelian
      randomisation study on 310,000 UK Biobank participants.
AB  - BACKGROUND: Observational studies have shown that being taller is associated with
      greater cancer risk. However, the interpretation of such studies can be hampered
      by important issues such as confounding and reporting bias. METHODS: We used the
      UK Biobank resource to develop genetic predictors of height and applied these in
      a Mendelian randomisation framework to estimate the causal relationship between
      height and cancer. Up to 438,870 UK Biobank participants were considered in our
      analysis. We addressed two primary cancer outcomes, cancer incidence by age ~60
      and cancer mortality by age ~60 (where age ~60 is the typical age of UK Biobank
      participants). RESULTS: We found that each genetically predicted 9 cm increase in
      height conferred an odds ratio of 1.10 (95% confidence interval 1.07-1.13) and
      1.09 (1.02-1.16) for diagnosis of any cancer and death from any cancer,
      respectively. For both risk and mortality, the effect was larger in females than
      in males. CONCLUSIONS: Height increases the risk of being diagnosed with and
      dying from cancer. These findings from Mendelian randomisation analyses agree
      with observational studies and provide evidence that they were not likely to have
      been strongly affected by confounding or reporting bias.

PMID- 29581485
TI  - Cooperative communication within and between single nanocatalysts.
AB  - Enzymes often show catalytic allostery in which reactions occurring at different
      sites communicate cooperatively over distances of up to a few nanometres. Whether
      such effects can occur with non-biological nanocatalysts remains unclear, even
      though these nanocatalysts can undergo restructuring and molecules can diffuse
      over catalyst surfaces. Here we report that phenomenologically similar, but
      mechanistically distinct, cooperative effects indeed exist for nanocatalysts.
      Using spatiotemporally resolved single-molecule catalysis imaging, we find that
      catalytic reactions on a single Pd or Au nanocatalyst can communicate with each
      other, probably via hopping of positively charged holes on the catalyst surface,
      over ~102 nanometres and with a temporal memory of ~101 to 102 seconds, giving
      rise to positive cooperativity among its surface active sites. Similar
      communication is also observed between individual nanocatalysts, however it
      operates via a molecular diffusion mechanism involving negatively charged product
      molecules, and its communication distance is many micrometres. Generalization of
      these long-range intra- and interparticle catalytic communication mechanisms may
      introduce a novel conceptual framework for understanding nanoscale catalysis.

PMID- 29581484
TI  - Oxidative [4+2] annulation of styrenes with alkynes under external-oxidant-free
      conditions.
AB  - The sequenced Diels-Alder/oxidation reaction represents a powerful route for the
      construction of aromatic compounds in organic synthesis. The oxidative Diels
      Alder reaction with H2 evolution would be a more ideal approach that can avoid
      the additional oxidation procedure and stoichiometric oxidant. Herein, an
      oxidative [4 + 2] annulation reaction of styrene derivatives with electron-rich
      dienophiles accompanying the H2 generation has been developed by using the
      synergistic merger of photoredox and cobaloxime catalyst. With respect to atom
      and step-economy ideals, this dual catalytic system enables the formation of high
      value molecules from feedstock chemicals in a single step under room temperature.

PMID- 29581486
TI  - Distinct thermodynamic signatures of oligomer generation in the aggregation of
      the amyloid-beta peptide.
AB  - Mapping free-energy landscapes has proved to be a powerful tool for studying
      reaction mechanisms. Many complex biomolecular assembly processes, however, have
      remained challenging to access using this approach, including the aggregation of
      peptides and proteins into amyloid fibrils implicated in a range of disorders.
      Here, we generalize the strategy used to probe free-energy landscapes in protein
      folding to determine the activation energies and entropies that characterize each
      of the molecular steps in the aggregation of the amyloid-beta peptide (Abeta42),
      which is associated with Alzheimer's disease. Our results reveal that
      interactions between monomeric Abeta42 and amyloid fibrils during fibril
      dependent secondary nucleation fundamentally reverse the thermodynamic signature
      of this process relative to primary nucleation, even though both processes
      generate aggregates from soluble peptides. By mapping the energetic and entropic
      contributions along the reaction trajectories, we show that the catalytic
      efficiency of Abeta42 fibril surfaces results from the enthalpic stabilization of
      adsorbing peptides in conformations amenable to nucleation, resulting in a
      dramatic lowering of the activation energy for nucleation.

PMID- 29581488
TI  - Infused ice can multiply IceCube's sensitivity.
AB  - The IceCube Neutrino Observatory is the world's largest neutrino detector with a
      cubic-kilometer instrumented volume at the South Pole. It is preparing for a
      major upgrade that will significantly increase its sensitivity. A promising
      technological innovation investigated for this upgrade is wavelength shifting
      optics. Augmenting sensors with such optics could increase the photo-collection
      area of IceCube's digital optical modules, and shift the incoming photons'
      wavelength to where these modules are the most sensitive. Here we investigate the
      use of IceCube's drill holes as wavelength shifting optics. We calculate the
      sensitivity enhancement due to increasing the ice's refractive index in the
      holes, and infusing wavelength-shifting substrate into the ice. We find that,
      with adequate wavelength-shifter infusion, every ~0.05 increase in the ice's
      refractive index will increase IceCube's photon sensitivity by 100%, opening the
      possibility for the substantial, cost-effective expansion of IceCube's reach.

PMID- 29581489
TI  - The USDA's recently released tech notes: A review.

PMID- 29581487
TI  - A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung
      inflammation via aryl hydrocarbon receptor.
AB  - Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated
      with asthma, but its regulatory mechanisms remain incompletely defined. We report
      herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH
      exposure, were found in asthmatic subjects (n = 39) as compared to those in
      healthy subjects (n = 43) living in an industrial city of Taiwan, where
      indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with
      ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses
      of IP significantly enhanced antigen-induced allergic inflammation, including
      increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as
      antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl
      hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly
      altered DC's function, including increased level of pro-inflammatory IL-6 and
      decreased generation of anti-inflammatory IL-10. The IP's effect was lost in DCs
      from mice carrying an AhR-mutant allele. Taken together, these results suggest
      that chronic exposure to environmental PAHs may pose a significant risk for
      asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the
      severity of allergic lung inflammation in mice through, at least in part, its
      ability in modulating DC's function in an AhR-dependent manner.

PMID- 29581491
TI  - Unnecessary tension.

PMID- 29581492
TI  - Is 'saving money' a valid justification?

PMID- 29581493
TI  - The use of used.

PMID- 29581494
TI  - A Word from OLAW.

PMID- 29581495
TI  - Unfortunate but not noncompliant.

PMID- 29581496
TI  - The sequence of the salamander.

PMID- 29581498
TI  - Breaking down behavior.

PMID- 29581497
TI  - The Marmorkrebs model.

PMID- 29581499
TI  - A space evaluation.

PMID- 29581500
TI  - Pupils protecting sleep.

PMID- 29581501
TI  - Neuron holography.

PMID- 29581502
TI  - Fish food & tumor growth.

PMID- 29581503
TI  - An antiviral STING.

PMID- 29581504
TI  - Testing for torpor.

PMID- 29581505
TI  - On the hunt.

PMID- 29581506
TI  - An amino acid to SORT the brain's proteome.

PMID- 29581507
TI  - The ageless bat.

PMID- 29581508
TI  - Bat research takes wing.
AB  - In the field and in the lab, scientists across the globe are working to better
      understand the biology of the bat.

PMID- 29581510
TI  - Resolve barley domestication.

PMID- 29581509
TI  - The RNA-binding protein ARPP21 controls dendritic branching by functionally
      opposing the miRNA it hosts.
AB  - About half of mammalian miRNA genes lie within introns of protein-coding genes,
      yet little is known about functional interactions between miRNAs and their host
      genes. The intronic miRNA miR-128 regulates neuronal excitability and dendritic
      morphology of principal neurons during mouse cerebral cortex development. Its
      conserved host genes, R3hdm1 and Arpp21, are predicted RNA-binding proteins. Here
      we use iCLIP to characterize ARPP21 recognition of uridine-rich sequences with
      high specificity for 3'UTRs. ARPP21 antagonizes miR-128 activity by co-regulating
      a subset of miR-128 target mRNAs enriched for neurodevelopmental functions.
      Protein-protein interaction data and functional assays suggest that ARPP21 acts
      as a positive post-transcriptional regulator by interacting with the translation
      initiation complex eIF4F. This molecular antagonism is reflected in inverse
      activities during dendritogenesis: miR-128 overexpression or knockdown of ARPP21
      reduces dendritic complexity; ectopic ARPP21 leads to an increase. Thus, we
      describe a unique example of convergent function by two products of a single
      gene.

PMID- 29581512
TI  - Learning from CIK plants.

PMID- 29581511
TI  - A group of receptor kinases are essential for CLAVATA signalling to maintain stem
      cell homeostasis.
AB  - Continuous organ initiation and outgrowth in plants relies on the proliferation
      and differentiation of stem cells maintained by the CLAVATA (CLV)-WUSCHEL (WUS)
      negative-feedback loop1-3. Leucine-rich repeat receptor-like protein kinases (LRR
      RLKs), including CLV1, BARELY ANY MERISTEMS and RECEPTOR-LIKE PROTEIN KINASE 2
      (RPK2), a receptor-like protein CLV2 and a pseudokinase CORYNE (CRN) are involved
      in the perception of the CLV3 signal to repress WUS expression4-10. WUS, a
      homeodomain transcription factor, in turn directly activates CLV3 expression and
      promotes stem cell activity in the shoot apical meristem11,12. However, the
      signalling mechanism immediately following the perception of CLV3 by its
      receptors is poorly understood. Here, we show that a group of LRR-RLKs,
      designated as CLAVATA3 INSENSITIVE RECEPTOR KINASES (CIKs), have essential roles
      in regulating CLV3-mediated stem cell homeostasis. The cik1 2 3 4 quadruple
      mutant exhibits a significantly enlarged SAM, resembling clv mutants. Genetic
      analyses and biochemical assays demonstrated that CIKs function as co-receptors
      of CLV1, CLV2/CRN and RPK2 to mediate CLV3 signalling through phosphorylation.
      Our findings not only widen the understanding of the underlying mechanism of CLV3
      signal transduction in regulating stem cell fate but also reveal a novel group of
      RLKs that function as co-receptors to possibly mediate multiple extrinsic and
      intrinsic signals during plant growth and development.

PMID- 29581513
TI  - The CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by
      targeting STAT1 for degradation.
AB  - Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein.
      Although roles for Intu have been reported during embryonic development and in
      the context of developmental disorders, its function and regulation in adult
      tissues remain poorly understood. Here we show that ablation of Intu specifically
      in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and
      leads to defective post-injury ciliogenesis. We identify signal transducer and
      activator of transcription 1 (STAT1) as a novel interacting partner of Intu. In
      vitro, Intu and STAT1 colocalize at the centriole/basal body area, and Intu
      promotes proteasomal degradation of STAT1. During cell stress, Intu expression
      preserves cilia length and cell viability, and these actions are antagonized by
      STAT1 expression. Thus, we propose a role for Intu in protecting cells and
      tissues after injury by targeting STAT1 for degradation and maintaining primary
      cilia.

PMID- 29581514
TI  - Structure and Dynamics of Polymeric Canopies in Nanoscale Ionic Materials: An
      Electrical Double Layer Perspective.
AB  - Nanoscale ionic materials (NIMs) are an emerging class of materials consisting of
      charged nanoparticles and polymeric canopies attaching to them dynamically by
      electrostatic interactions. Using molecular simulations, we examine the structure
      and dynamics of the polymeric canopies in model NIMs in which the canopy
      thickness is much smaller than the nanoparticle diameter. Without added
      electrolyte ions, the charged terminal groups of polymers adsorb strongly on
      charged walls, thereby electrostatically "grafting" polymers to the wall. These
      polymers are highly stretched. They rarely desorb from the wall, but maintain
      modest in-plane mobility. When electrolyte ion pairs are introduced, the
      counterions adsorb on the wall, causing some electrostatically "grafted" polymers
      to desorb. The desorbed polymers, however, are less than the adsorbed counter
      ions, which leads to an overscreening of wall charges. The desorbed polymers'
      charged terminal groups do not distribute uniformly across the canopy but are
      depleted in some regions; they adopt conformation similar to those in bulk and
      exchange with the "grafted" polymers rapidly, hence dilating the canopy and
      accelerating its dynamics. We understand these results by taking the canopy as an
      electrical double layer, and highlight the importance of the interplay of
      electrostatic and entropic effects in determining its structure and dynamics.

PMID- 29581515
TI  - Mentha-Stabilized Silver Nanoparticles for High-Performance Colorimetric
      Detection of Al(III) in Aqueous Systems.
AB  - The present paper reports a facile and selective colorimetric method for the
      detection of potential environmental and health hazardous metal ions using green
      synthesized silver nanoparticles (AgNPs). Here the organic functional groups
      present in the plant extract (Mentha arvensis) are used as reductants and
      stabilizers in the synthesis of AgNPs. They also provide a suitable binding site
      to the (Al(III)) analyte in the detection mechanism. The leaf extract of Mentha
      arvensis was used to synthesize AgNPs at room-temperature and at 80  degrees C.
      The AgNPs synthesized at 80  degrees C exhibit excellent selective colorimetric
      detection of Al(III). The as-synthesized AgNPs have been characterized, and the
      synthesis, stabilization of NPs and detection mechanism has also been illustrated
      by using UV-vis, XPS, FTIR, TEM, EDX, SEM, AAS, and TGA analytical tools and
      techniques. The selectivity of detection probe was supported by the reaction
      between probe and metal ions followed first-order kinetics having the highest
      value of the regression coefficient (R2 = 0.99) for Al(III) and the analysis of
      thermodynamic parameters. The prepared sensor showed a lower limit of detection
      (LOD) of 1 nM (S/N = 3.2) in real water samples. The proposed method can be
      successfully utilized for the detection of Al(III) from both drinking and real
      water samples at the nanomolar level.

PMID- 29581516
TI  - Analysis of microsatellites from transcriptome sequences of Phytophthora capsici
      and applications for population studies.
AB  - Phytophthora capsici is a devastating oomycete that affects solanaceous,
      cucurbitaceous, fabaceous, and other crops in the United States (US) and
      worldwide. The release of the P. capsici genome allows for design of robust
      markers for genetic studies. We identified and characterized microsatellites in
      the P. capsici transcriptome. A subset of 50 microsatellites were assayed in a
      diverse set of P. capsici isolates and evaluated for polymorphism. Polymorphic
      microsatellites were confirmed by fragment analysis, and 12 were used for
      population characterization of 50 P. capsici isolates from different states,
      hosts, and mating types. Analysis of genetic relationship among isolates revealed
      significant geographic structure by state. Our findings highlight the usefulness
      of these 12 microsatellites to characterize the population structure of P.
      capsici and potential transferability to closely-related Phytophthora spp. since
      markers are located in coding regions. Our markers will facilitate genetic
      characterization and complement phenotypic studies of P. capsici populations,
      which may assist in deployment of disease management strategies.

PMID- 29581517
TI  - Elia Kazan's America America: A Message for America.
AB  - Elia Kazan's 1963 film, America America is a tribute to the immigrant experience
      of his own forebears, and has relevance to the refugee crisis of today. In stark
      black and white cinematography, the film provides insight into the refugee
      immigrant experience, personified in Stavros, a young man longing for freedom,
      obsessed with an idealized America. His hope and innocence cannot safeguard him.
      His memories of his happy childhood and loving family create idealizing
      transferences to a world of others who manipulate and betray him as he undertakes
      his quest. Eventually he too learns to manipulate and betray, unconsciously
      identifying with the aggressor. History will offer ethical challenges, the black
      and white cinematography mirroring the black and white perception of good and
      bad, the shades of grey evoking a maturation of understanding.

PMID- 29581518
TI  - Depressive mood in individuals with spinal cord injury (SCI) living in Greece.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To provide data on depressive
      symptoms rates in the Greek SCI population and to investigate their association
      with demographic and clinical variables. SETTING: Greek territory. METHODS: One
      hundred and sixty-four individuals with SCI living in the community for at least
      1 year after the completion of the primary inpatient rehabilitation program were
      included in the study. Our group of participants were enrolled from multiple
      rehabilitation centers throughout Greece and were evaluated for probable
      depression according to the Patient Health Questionnaire (PHQ-9). Univariable and
      multiple linear regression analyses were performed to assess the possible
      association of risk factors with the occurrence of depression. We had also
      examined the correlation between PHQ-9 and scales measuring social reintegration
      (Craig Handicap Assessment and Reporting Technique (CHART)), quality of life
      (World Health Organization Quality of Life BREF (WHOQOL-BREF)), and independence
      (Spinal Cord Independence Measure (SCIM)). RESULTS: It was found that 18.2% of
      the sample had probable depression. The mean (SD) PHQ-9 score was 5.7  (4.9). The
      multiple linear regression analysis showed that high pain scores (P = 0.001) and
      suffering from both nociceptive and neuropathic pain (P = 0.005) were associated
      with depressive mood, while pressure ulcers had a significant effect (P = 0.049)
      only in the univariable analysis. Participant's PHQ-9 scores had also a negative
      correlation with almost all CHART, WHOQOL-BREF, and SCIM subscales' scores.
      CONCLUSIONS: This study documents relatively low rates of probable depression
      among individuals with SCI in Greece. Severe pain and pressure ulcers were the
      main identified predictors of depressive mood.

PMID- 29581519
TI  - Internet-delivered mindfulness for people with depression and chronic pain
      following spinal cord injury: a randomized, controlled feasibility trial.
AB  - STUDY DESIGN: Between-subjects, randomized controlled feasibility study.
      OBJECTIVES: Populations with reduced sensory and motor function are at increased
      risk of depression, anxiety and pain, and may be less geographically mobile. This
      study explored the efficacy and feasibility of web-based mindfulness training for
      people with spinal cord injury (SCI). SETTING: UK community sample. METHODS:
      Participants were randomly allocated to an 8-week online mindfulness intervention
      (N = 36), or to internet-delivered psychoeducation (N = 31). Depression symptom
      severity was the primary outcome. Secondary outcomes included anxiety, quality of
      life (QoL), pain perception, pain catastrophizing and mindfulness. Measures were
      taken before (T1), at completion of, (T2), and 3 months following the
      intervention (T3). RESULTS: At T2, ten participants discontinued mindfulness
      training, and five discontinued psychoeducation. Dropouts were of significantly
      older age. Nine participants were lost to follow-up. Mindfulness reduced
      depression significantly more than psychoeducation at T2 (mean difference = 
      1.50, 95% CI [-2.43, -0.58]) and T3 (mean difference = -2.34, 95% CI [-3.62, 
      1.10]). Anxiety, pain unpleasantness and catastrophizing were significantly
      reduced compared with psychoeducation. Total mindfulness scores, and all facets
      of mindfulness except observing were significantly higher following mindfulness
      training. At follow-up, reductions in anxiety and catastrophizing persisted.
      CONCLUSIONS: Internet-delivered mindfulness training offers unique benefits and
      is viable for people with reduced sensory awareness. Future work should explore
      the feasibility of combined education and mindfulness training. The use of brief
      interventions shows promise in maximizing participant retention.

PMID- 29581520
TI  - Predicting Urban Reservoir Levels Using Statistical Learning Techniques.
AB  - Urban water supplies are critical to the growth of the city and the wellbeing of
      its citizens. However, these supplies can be vulnerable to hydrological extremes,
      such as droughts and floods, especially if they are the main source of water for
      the city. Maintaining these supplies and preparing for future conditions is a
      crucial task for water managers, but predicting hydrological extremes is a
      challenge. This study tested the abilities of eight statistical learning
      techniques to predict reservoir levels, given the current hydroclimatic
      conditions, and provide inferences on the key predictors of reservoir levels. The
      results showed that random forest, an ensemble, tree-based method, was the best
      algorithm for predicting reservoir levels. We initially developed the models
      using Lake Sidney Lanier (Atlanta, Georgia) as the test site; however, further
      analysis demonstrated that the model based on the random forest algorithm was
      transferable to other reservoirs, specifically Eagle Creek (Indianapolis,
      Indiana) and Lake Travis (Austin, Texas). Additionally, we found that although
      each reservoir was impacted differently, streamflow, city population, and El
      Nino/Southern Oscillation (ENSO) index were repeatedly among the most important
      predictors. These are critical variables which can be used by water managers to
      recognize the potential for reservoir level changes.

PMID- 29581521
TI  - The effects of host species and sexual dimorphism differ among root, leaf and
      flower microbiomes of wild strawberries in situ.
AB  - Plant-associated microbiomes profoundly influence host interactions with below-
      and aboveground environments. Characterizing plant-associated microbiomes in
      experimental settings have revealed important drivers of microbiota assemblies
      within host species. However, it remains unclear how important these individual
      drivers (e.g., organ type, host species, host sexual phenotype) are in
      structuring the patterns of plant-microbiota association in the wild. Using 16s
      rRNA sequencing, we characterized root, leaf and flower microbiomes in three
      closely related, sexually polymorphic Fragaria species, in the broadly sympatric
      portion of their native ranges in Oregon, USA. Taking into account the potential
      influence of broad-scale abiotic environments, we found that organ type explained
      the largest variation of compositional and phylogenetic alpha- and beta-diversity
      of bacterial communities in these wild populations, and its overall effect
      exceeded that of host species and host sex. Yet, the influence of host species
      increased from root to leaf to flower microbiomes. We detected strong sexual
      dimorphism in flower and leaf microbiomes, especially in host species with the
      most complete separation of sexes. Our results provide the first demonstration of
      enhanced influence of host species and sexual dimorphism from root to flower
      microbiomes, which may be applicable to many other plants in the wild.

PMID- 29581522
TI  - Relationship between age and surgical success after trabeculectomy with
      adjunctive mitomycin C.
AB  - PURPOSE: To investigate whether there is any effect of age on bleb morphology and
      surgical success after trabeculectomy with adjunctive Mitomycin C (MMC). METHODS:
      A total 143 eyes of 123 patients were divided into two groups: group 1 ( <= 60
      years old, n = 85) and group 2 ( > 60 years old, n = 58). Kaplan-Meier survival
      curve analysis was used to assess long-term surgical success according to
      "complete success" (intraocular pressure (IOP) reduction >= 30% without
      medications) and "qualified success" criteria (IOP reduction >= 30%, with or
      without medications) between the two groups. Cox proportional hazard models were
      used to examine the factors associated with surgical success. Bleb morphology was
      evaluated by height, extent and vascularity at postoperative 1 month, 3 months, 6
      months, and 12 months. RESULTS: The younger-age group (group 1) showed
      significantly better results, in terms of both complete success and qualified
      success, than did the older-age group (group 2) (p < 0.001 and p = 0.01,
      respectively). Age and preoperative anti-glaucoma medications were the factors
      related to complete success (p = 0.001). Also, there were significant differences
      in height, extent and vascularity of bleb between the two groups (p = 0.038, p =
      0.002 and p = 0.006, respectively). CONCLUSION: The long-term surgical outcome
      after trabeculectomy with MMC was better in the younger-age group than in the
      older-age group. Specifically, the younger-age group showed a more prominent and
      more localized bleb with less vascularity.

PMID- 29581523
TI  - Do patients only remember who performed their cataract surgery if complications
      occur?

PMID- 29581524
TI  - Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated
      Cognitive Impairment through ATF6-Herp Signaling.
AB  - Chronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy)
      levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy
      enhances oxidative stress and blood-brain-barrier (BBB) disruption through
      modulation of endoplasmic reticulum (ER) stress; in part by epigenetic
      alternation, leading to cognitive impairment. Clinicians have recommended
      exercise as a therapy; however, its protective effect on cognitive functions has
      not been fully explored. The present study was designed to observe the protective
      effects of exercise (EX) against alcohol-induced epigenetic and molecular
      alterations leading to cerebrovascular dysfunction. Wild-type mice were subjected
      to AL administration (1.5 g/kg-bw) and subsequent treadmill EX for 12 weeks (5
      day/week@7-11 m/min). AL affected mouse brain through increases in oxidative and
      ER stress markers, SAHH and DNMTs alternation, while decreases in CBS, CSE,
      MTHFR, tight-junction proteins and cellular H2S levels. Mechanistic study
      revealed that AL increased epigenetic DNA hypomethylation of Herp promoter. BBB
      dysfunction and cognitive impairment were observed in the AL treated mice. AL
      mediated transcriptional changes were abolished by administration of ER stress
      inhibitor DTT. In conclusion, exercise restored Hcy and H2S to basal levels while
      ameliorating AL-induced ER stress, diminishing BBB dysfunction and improving
      cognitive function via ATF6-Herp-signaling. EX showed its protective efficacy
      against AL-induced neurotoxicity.

PMID- 29581525
TI  - Innate immune system activation in zebrafish and cellular models of Diamond
      Blackfan Anemia.
AB  - Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA)
      associated with anemia, congenital defects, and cancer. While p53 activation is
      responsible for many features of DBA, the role of immune system is less defined.
      The Innate immune system can be activated by endogenous nucleic acids from non
      processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by
      toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and
      inflammation. Dying cells can also activate complement system. Therefore we
      analyzed the status of these pathways in RP-deficient zebrafish and found
      upregulation of interferon, inflammatory cytokines and mediators, and complement.
      We also found upregulation of receptors signaling to IFNs including Mda5, Tlr3,
      and Tlr9. TGFb family member activin was also upregulated in RP-deficient
      zebrafish and in RPS19-deficient human cells, which include a lymphoid cell line
      from a DBA patient, and fetal liver cells and K562 cells transduced with RPS19
      shRNA. Treatment of RP-deficient zebrafish with a TLR3 inhibitor decreased IFNs
      activation, acute phase response, and apoptosis and improved their hematopoiesis
      and morphology. Inhibitors of complement and activin also had beneficial effects.
      Our studies suggest that innate immune system contributes to the phenotype of
      RPS19-deficient zebrafish and human cells.

PMID- 29581526
TI  - HDAC genes play distinct and redundant roles in Cryptococcus neoformans
      virulence.
AB  - The human fungal pathogen Cryptococcus neoformans undergoes many phenotypic
      changes to promote its survival in specific ecological niches and inside the
      host. To explore the role of chromatin remodeling on the expression of virulence
      related traits, we identified and deleted seven genes encoding predicted class
      I/II histone deacetylases (HDACs) in the C. neoformans genome. These studies
      demonstrated that individual HDACs control non-identical but overlapping cellular
      processes associated with virulence, including thermotolerance, capsule
      formation, melanin synthesis, protease activity and cell wall integrity. We also
      determined the HDAC genes necessary for C. neoformans survival during in vitro
      macrophage infection and in animal models of cryptococcosis. Our results
      identified the HDA1 HDAC gene as a central mediator controlling several cellular
      processes, including mating and virulence. Finally, a global gene expression
      profile comparing the hda1Delta mutant versus wild-type revealed altered
      transcription of specific genes associated with the most prominent virulence
      attributes in this fungal pathogen. This study directly correlates the effects of
      Class I/II HDAC-mediated chromatin remodeling on the marked phenotypic plasticity
      and virulence potential of this microorganism. Furthermore, our results provide
      insights into regulatory mechanisms involved in virulence gene expression that
      are likely shared with other microbial pathogens.

PMID- 29581528
TI  - Non-linear phonon Peltier effect in dissipative quantum dot systems.
AB  - Solid state thermoelectric cooling is based on the electronic Peltier effect,
      which cools via an electronic heat current in the absence of an applied
      temperature gradient. In this work, we demonstrate that equivalently, a phonon
      Peltier effect may arise in the non-linear thermoelectric transport regime of a
      dissipative quantum dot thermoelectric setup described via Anderson-Holstein
      model. This effect leads to an electron induced phonon heat current in the
      absence of a thermal gradient. Utilizing the modification of quasi-equilibrium
      phonon distribution via charge induced phonon accumulation, we show that in a
      special case the polarity of the phonon heat current can be reversed so that
      setup can dump heat into the hotter reservoirs. In further exploring
      possibilities that can arise from this effect, we propose a novel charge-induced
      phonon switching mechanism that may be incited via electrostatic gating.

PMID- 29581527
TI  - Identification of an Arg-Leu-Arg tripeptide that contributes to the binding
      interface between the cytokine MIF and the chemokine receptor CXCR4.
AB  - MIF is a chemokine-like cytokine that plays a role in the pathogenesis of
      inflammatory and cardiovascular disorders. It binds to the chemokine-receptors
      CXCR2/CXCR4 to trigger atherogenic leukocyte migration albeit lacking canonical
      chemokine structures. We recently characterized an N-like-loop and the Pro-2
      residue of MIF as critical molecular determinants of the CXCR4/MIF binding-site
      and identified allosteric agonism as a mechanism that distinguishes CXCR4-binding
      to MIF from that to the cognate ligand CXCL12. By using peptide spot-array
      technology, site-directed mutagenesis, structure-activity-relationships, and
      molecular docking, we identified the Arg-Leu-Arg (RLR) sequence-region 87-89 that
      - in three-dimensional space - 'extends' the N-like-loop to control site-1
      binding to CXCR4. Contrary to wildtype MIF, mutant R87A-L88A-R89A-MIF fails to
      bind to the N-terminal of CXCR4 and the contribution of RLR to the MIF/CXCR4
      interaction is underpinned by an ablation of MIF/CXCR4-specific signaling and
      reduction in CXCR4-dependent chemotactic leukocyte migration of the RLR-mutant of
      MIF. Alanine-scanning, functional competition by RLR-containing peptides, and
      molecular docking indicate that the RLR residues directly participate in contacts
      between MIF and CXCR4 and highlight the importance of charge-interactions at this
      interface. Identification of the RLR region adds important structural information
      to the MIF/CXCR4 binding-site that distinguishes this interface from CXCR4/CXCL12
      and will help to design MIF-specific drug-targeting approaches.

PMID- 29581529
TI  - Enhanced protection of the renal vascular endothelium improves early outcome in
      kidney transplantation: Preclinical investigations in pig and mouse.
AB  - Ischemia reperfusion injury is one of the major complications responsible for
      delayed graft function in kidney transplantation. Applications to reduce
      reperfusion injury are essential due to the widespread use of kidneys from
      deceased organ donors where the risk for delayed graft function is especially
      prominent. We have recently shown that coating of inflamed or damaged endothelial
      cells with a unique heparin conjugate reduces thrombosis and leukocyte
      recruitment. In this study we evaluated the binding capacity of the heparin
      conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine
      donors, and to murine kidneys during static cold storage. The heparin conjugate
      was able to stably bind cultured endothelial cells with high avidity, and to the
      renal vasculature of explanted kidneys from pigs and mice. Treatment of murine
      kidneys prior to transplantation reduced platelet deposition and leukocyte
      infiltration 24 hours post-transplantation, and significantly improved graft
      function. The present study thus shows the benefits of enhanced protection of the
      renal vasculature during cold storage, whereby increasing the antithrombotic and
      anti-adhesive properties of the vascular endothelium yields improved renal
      function early after transplantation.

PMID- 29581530
TI  - Genomic expansion of magnetotactic bacteria reveals an early common origin of
      magnetotaxis with lineage-specific evolution.
AB  - The origin and evolution of magnetoreception, which in diverse prokaryotes and
      protozoa is known as magnetotaxis and enables these microorganisms to detect
      Earth's magnetic field for orientation and navigation, is not well understood in
      evolutionary biology. The only known prokaryotes capable of sensing the
      geomagnetic field are magnetotactic bacteria (MTB), motile microorganisms that
      biomineralize intracellular, membrane-bounded magnetic single-domain crystals of
      either magnetite (Fe3O4) or greigite (Fe3S4) called magnetosomes. Magnetosomes
      are responsible for magnetotaxis in MTB. Here we report the first large-scale
      metagenomic survey of MTB from both northern and southern hemispheres combined
      with 28 genomes from uncultivated MTB. These genomes expand greatly the coverage
      of MTB in the Proteobacteria, Nitrospirae, and Omnitrophica phyla, and provide
      the first genomic evidence of MTB belonging to the Zetaproteobacteria and
      "Candidatus Lambdaproteobacteria" classes. The gene content and organization of
      magnetosome gene clusters, which are physically grouped genes that encode
      proteins for magnetosome biosynthesis and organization, are more conserved within
      phylogenetically similar groups than between different taxonomic lineages.
      Moreover, the phylogenies of core magnetosome proteins form monophyletic clades.
      Together, these results suggest a common ancient origin of iron-based (Fe3O4 and
      Fe3S4) magnetotaxis in the domain Bacteria that underwent lineage-specific
      evolution, shedding new light on the origin and evolution of biomineralization
      and magnetotaxis, and expanding significantly the phylogenomic representation of
      MTB.

PMID- 29581531
TI  - Bi-directional coupling in strain-mediated multiferroic heterostructures with
      magnetic domains and domain wall motion.
AB  - Strain-coupled multiferroic heterostructures provide a path to energy-efficient,
      voltage-controlled magnetic nanoscale devices, a region where current-based
      methods of magnetic control suffer from Ohmic dissipation. Growing interest in
      highly magnetoelastic materials, such as Terfenol-D, prompts a more accurate
      understanding of their magnetization behavior. To address this need, we simulate
      the strain-induced magnetization change with two modeling methods: the commonly
      used unidirectional model and the recently developed bidirectional model.
      Unidirectional models account for magnetoelastic effects only, while
      bidirectional models account for both magnetoelastic and magnetostrictive
      effects. We found unidirectional models are on par with bidirectional models when
      describing the magnetic behavior in weakly magnetoelastic materials (e.g.,
      Nickel), but the two models deviate when highly magnetoelastic materials (e.g.,
      Terfenol-D) are introduced. These results suggest that magnetostrictive feedback
      is critical for modeling highly magnetoelastic materials, as opposed to weaker
      magnetoelastic materials, where we observe only minor differences between the two
      methods' outputs. To our best knowledge, this work represents the first
      comparison of unidirectional and bidirectional modeling in composite multiferroic
      systems, demonstrating that back-coupling of magnetization to strain can inhibit
      formation and rotation of magnetic states, highlighting the need to revisit the
      assumption that unidirectional modeling always captures the necessary physics in
      strain-mediated multiferroics.

PMID- 29581532
TI  - C-type lectins in immunity and homeostasis.
AB  - The C-type lectins are a superfamily of proteins that recognize a broad
      repertoire of ligands and that regulate a diverse range of physiological
      functions. Most research attention has focused on the ability of C-type lectins
      to function in innate and adaptive antimicrobial immune responses, but these
      proteins are increasingly being recognized to have a major role in autoimmune
      diseases and to contribute to many other aspects of multicellular existence.
      Defects in these molecules lead to developmental and physiological abnormalities,
      as well as altered susceptibility to infectious and non-infectious diseases. In
      this Review, we present an overview of the roles of C-type lectins in immunity
      and homeostasis, with an emphasis on the most exciting recent discoveries.

PMID- 29581533
TI  - Highly efficient Fenton and enzyme-mimetic activities of NH2-MIL-88B(Fe) metal
      organic framework for methylene blue degradation.
AB  - Here, we show that NH2-MIL-88B(Fe) can be used as a peroxidase-like catalyst for
      Fenton-like degradation of methylene blue (MB) in water. The iron-based NH2-MIL
      88B(Fe) metal organic framework (MOF) was synthesized by a facile and rapid
      microwave heating method. It was characterized by scanning electron microscopy,
      Fourier transform infrared spectroscopy, powder X-ray diffraction, and the
      Brunauer-Emmett-Teller method. The NH2-MIL-88B(Fe) MOF possesses intrinsic
      oxidase-like and peroxidase-like activities. The reaction parameters that affect
      MB degradation were investigated, including the solution pH, NH2-MIL-88B(Fe) MOF
      and H2O2 concentrations, and temperature. The results show that the NH2-MIL
      88B(Fe) MOF exhibits a wide working pH range (pH 3.0-11.0), temperature
      tolerance, and good recyclability for MB removal. Under the optimal conditions,
      complete removal of MB was achieved within 45 min. In addition, removal of MB was
      above 80% after five cycles, showing the good recyclability of NH2-MIL-88B(Fe).
      The NH2-MIL-88B(Fe) MOF has the features of easy preparation, high efficiency,
      and good recyclability for MB removal in a wide pH range. Electron spin resonance
      and fluorescence probe results suggest the involvement of hydroxyl radicals in MB
      degradation. These findings provide new insight into the application of high
      efficient MOF-based Fenton-like catalysts for water purification.

PMID- 29581534
TI  - MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2
      in esophageal squamous cell carcinoma.
AB  - MicroRNAs play an important role in the migration and invasion of tumors, and
      lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant
      tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we
      found that miR-1 expression levels in tumor tissues and preoperative serum from
      esophageal carcinoma patients were lower than those in non-tumorous tissues and
      healthy volunteers. miR-1 expression in tissues and plasma was closely related to
      invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression
      levels in tissues and plasma were positively correlated. miR-1 inhibited cell
      proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells
      reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to
      an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment
      validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into
      cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration
      and invasion. Further studies verified that miR-1 regulates EMT signalling
      pathways directly through Notch2. Therefore, these results confirm that, as a
      tumor suppressor gene, miR-1 may be a potential tumor marker for the early
      diagnosis of ESCC and a new drug target.

PMID- 29581535
TI  - Mitochondrial fragmentation affects neither the sensitivity to TNFalpha-induced
      apoptosis of Brucella-infected cells nor the intracellular replication of the
      bacteria.
AB  - Mitochondria are complex organelles that participate in many cellular functions,
      ranging from ATP production to immune responses against viruses and bacteria.
      This integration of a plethora of functions within a single organelle makes
      mitochondria a very attractive target to manipulate for intracellular pathogens.
      We characterised the crosstalk that exists between Brucella abortus, the
      causative agent of brucellosis, and the mitochondria of infected cells. Brucella
      replicates in a compartment derived from the endoplasmic reticulum (ER) and
      modulates ER functionality by activating the unfolded protein response. However,
      the impact of Brucella on the mitochondrial population of infected cells still
      requires a systematic study. We observed physical contacts between Brucella
      containing vacuoles and mitochondria. We also found that B. abortus replication
      is independent of mitochondrial oxidative phosphorylation and that mitochondrial
      reactive oxygen species do not participate to the control of B. abortus infection
      in vitro. We demonstrated that B. abortus and B. melitensis induce a drastic
      mitochondrial fragmentation at 48 hours post-infection in different cell types,
      including myeloid and non-myeloid cells. This fragmentation is DRP1-independent
      and might be caused by a deficit of mitochondrial fusion. However, mitochondrial
      fragmentation does not change neither Brucella replication efficiency, nor the
      susceptibility of infected cells to TNFalpha-induced apoptosis.

PMID- 29581536
TI  - Neural activation to monetary reward is associated with amphetamine reward
      sensitivity.
AB  - One known risk factor for drug use and abuse is sensitivity to rewarding effects
      of drugs. It is not known whether this risk factor extends to sensitivity to non
      drug rewards. In this study with healthy young adults, we examined the
      association between sensitivity to the subjective rewarding effects of
      amphetamine and a neural indicator of anticipation of monetary reward. We
      hypothesized that greater euphorigenic response to amphetamine would be
      associated with greater neural activation to anticipation of monetary reward (Win
      > Loss). Healthy participants (N = 61) completed four laboratory sessions in
      which they received d-amphetamine (20 mg) and placebo in alternating order,
      providing self-report measures of euphoria and stimulation at regular intervals.
      At a separate visit 1-3 weeks later, participants completed the guessing reward
      task (GRT) during fMRI in a drug-free state. Participants reporting greater
      euphoria after amphetamine also exhibited greater neural activation during
      monetary reward anticipation in mesolimbic reward regions, including the
      bilateral caudate and putamen. This is the first study to show a relationship
      between neural correlates of monetary reward and sensitivity to the subjective
      rewarding effects of amphetamine in humans. These findings support growing
      evidence that sensitivity to reward in general is a risk factor for drug use and
      abuse, and suggest that sensitivity of drug-induced euphoria may reflect a
      general sensitivity to rewards. This may be an index of vulnerability for drug
      use or abuse.

PMID- 29581539
TI  - Slab narrowing in the Central Mediterranean: the Calabro-Ionian subduction zone
      as imaged by high resolution seismic tomography.
AB  - A detailed 3D image of the Calabro-Ionian subduction system in the central
      Mediterranean was obtained by means of a seismic tomography, exploiting a large
      dataset of local earthquakes and computing algorithms able to build a dense grid
      of measure nodes. Results show that the slab is continuous below the southern
      sector of the Calabro-Peloritan Arc, but the deformation processes developing at
      its edges are leading to its progressive narrowing, influencing tectonics and
      magmatism at the surface, and with possible stress concentration in the tip
      zones. In the southwest, the deformation occurring at a free slab edge lead to
      propagation of a vertical lithospheric tear in the overriding plate, which
      extends along a NW-SE fault system (Aeolian-Tindari-Letojanni) up to about 30 km
      into the Ionian Sea; further southeast, the lithosphere appears only flexed and
      not broken yet. In the northeast, the slab seems to break progressively, parallel
      to the trench. Finally, northwest of Mt. Etna, the tomography highlights low VP
      that can be related to an upwelling of deep mantle material likely flowing
      laterally through a window opened by the complete slab detachment.

PMID- 29581538
TI  - Brain lactate and pH in schizophrenia and bipolar disorder: a systematic review
      of findings from magnetic resonance studies.
AB  - Converging evidence from molecular to neuroimaging studies suggests brain energy
      metabolism abnormalities in both schizophrenia and bipolar disorder. One emerging
      hypothesis is: decreased oxidative phosphorylation leading to accumulation of
      lactic acid from glycolysis and subsequent acidification of tissue. In this
      regard, integrating lactate and pH data from magnetic resonance spectroscopy
      (MRS) studies in both diseases may help us understand underlying neurobiological
      mechanisms. In order to achieve this goal, we performed a systematic search of
      case-control studies examining brain lactate or pH among schizophrenia and/or
      bipolar patients by using MRS. Medline/Pubmed and EBSCO databases were searched
      separately for both diseases and outcomes. Our search yielded 33 studies in total
      composed of 7 lactate and 26 pH studies. In bipolar disorder, 5 out of 6 studies
      have found elevated lactate levels especially in the cingulate cortex and 4 out
      of 13 studies reported reduced pH in the frontal lobe. In contrast, in
      schizophrenia a single study has examined lactate and reported elevation, while
      only 2 out of 13 studies examining pH have reported reduction in this measure.
      There were no consistent patterns for the relationship between lactate or pH
      levels and medication use, disease type, mood state, and other clinical
      variables. We highlight the need for future studies combining 1H-MRS and 31P-MRS
      approaches, using longitudinal designs to examine lactate and pH in disease
      progression across both schizophrenia and bipolar disorders.

PMID- 29581537
TI  - M1-positive allosteric modulators lacking agonist activity provide the optimal
      profile for enhancing cognition.
AB  - Highly selective positive allosteric modulators (PAMs) of the M1 subtype of
      muscarinic acetylcholine receptor have emerged as an exciting new approach for
      improving cognitive function in patients suffering from Alzheimer's disease and
      schizophrenia. However, excessive activation of M1 is known to induce seizure
      activity and have actions in the prefrontal cortex (PFC) that could impair
      cognitive function. We now report a series of pharmacological,
      electrophysiological, and behavioral studies in which we find that recently
      reported M1 PAMs, PF-06764427 and MK-7622, have robust agonist activity in cell
      lines and agonist effects in the mouse PFC, and have the potential to
      overactivate the M1 receptor and disrupt PFC function. In contrast, structurally
      distinct M1 PAMs (VU0453595 and VU0550164) are devoid of agonist activity in cell
      lines and maintain activity dependence of M1 activation in the PFC. Consistent
      with the previously reported effect of PF-06764427, the ago-PAM MK-7622 induces
      severe behavioral convulsions in mice. In contrast, VU0453595 does not induce
      behavioral convulsions at doses well above those required for maximal efficacy in
      enhancing cognitive function. Furthermore, in contrast to the robust efficacy of
      VU0453595, the ago-PAM MK-7622 failed to improve novel object recognition, a
      rodent assay of cognitive function. These findings suggest that in vivo cognition
      enhancing efficacy of M1 PAMs can be observed with PAMs lacking intrinsic agonist
      activity and that intrinsic agonist activity of M1 PAMs may contribute to adverse
      effects and reduced efficacy in improving cognitive function.

PMID- 29581540
TI  - Lower serum calcium is independently associated with CKD progression.
AB  - Disturbances in calcium metabolism are common in individuals with chronic kidney
      disease (CKD), but whether they are associated with subsequent kidney function
      decline is less clear. In a CKD 3-5 cohort of 15,755 adult citizens of Stockholm
      with creatinine tests taken during 2006-2011 and concurrent calcium testing at
      cohort entry, we investigated the association between baseline serum calcium and
      the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI)
      decline using linear mixed models. Mean (SD) baseline corrected serum calcium was
      9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was -0.82 (
      0.90; -0.74) mL/min/1.73 m2/year. In advanced CKD stages, higher baseline serum
      calcium was associated with less rapid kidney function decline. The adjusted
      change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline
      serum calcium was -0.10 (-0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (-0.02; 0.70) and
      0.68 (0.36; 1.00) mL/min/1.73 m2/year for individuals in CKD stage 3a, 3b, 4, and
      5, respectively. In a subgroup of patients using vitamin D supplements, the
      association between baseline serum calcium and CKD progression was eliminated,
      especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b
      to 5, lower baseline corrected serum calcium, rather than higher baseline serum
      calcium, associated with a more rapid CKD progression. Lower serum corrected
      calcium seems to be indicative for vitamin D deficiency.

PMID- 29581542
TI  - Detailed genomic characterization identifies high heterogeneity and histotype
      specific genomic profiles in adrenocortical carcinomas.
AB  - Molecular characterization of adrenocortical carcinoma has been recently
      established, but the correlation between molecular profiles and clinical and
      pathological characteristics is still poorly defined with no data available about
      genetic heterogeneity along disease progression. In this scenario, a detailed
      molecular profile was correlated with clinical and pathological characteristics
      in adrenocortical carcinoma patients to identify potentially novel biomarkers.
      Targeted next-generation sequencing and copy number variation analyses for 18
      most frequently altered genes in adrenocortical carcinoma were assessed on 62
      adult cases (including 10 with matched primary and metastatic/recurrence samples)
      and results correlated with major clinical and pathological characteristics of
      tumors. A total of 433 somatic deleterious genetic alterations (328 gene
      mutations and 105 copy number variations) were identified in 57/62 cases, five
      resulted wild type for all genes tested. TERT, CDK4, ZNRF3,and RB1 were altered
      in more than 30% of cases. Among histological variants genotypes were
      significantly different. Lowest mutation burden was found in the oncocytic type
      (p = 0.006), whereas the highest with a prevalence of RB1 (p = 0.001) and CDK4 (p
      = 0.002) was found in the conventional and myxoid ones, respectively. None of the
      10 cases with matched samples showed a stable genotype along tumor progression,
      although allelic frequencies or percentages of altered nuclei at fluorescence in
      situ hybridization were in most cases similar among different tumor samples for
      genes that were stable along tumor progression. Among individual genes, an
      altered p53/Rb1 pathway was the strongest adverse molecular signature, being
      associated with high Ki-67 index, high tumor stage, aggressive disease status,
      and shorter disease-free survival. The genomic signature in adrenocortical
      carcinoma is changing along tumor progression and is associated with specific
      clinical and pathological features, including histological variant and prognosis.

PMID- 29581541
TI  - Structure-based discovery of mPGES-1 inhibitors suitable for preclinical testing
      in wild-type mice as a new generation of anti-inflammatory drugs.
AB  - Human mPGES-1 is recognized as a promising target for next generation of anti
      inflammatory drugs without the side effects of currently available anti
      inflammatory drugs, and various inhibitors have been reported in the literature.
      However, none of the reported potent inhibitors of human mPGES-1 has shown to be
      also a potent inhibitor of mouse or rat mPGES-1, which prevents using the well
      established mouse/rat models of inflammation-related diseases for preclinical
      studies. Hence, despite of extensive efforts to design and discover various human
      mPGES-1 inhibitors, the promise of mPGES-1 as a target for the next generation of
      anti-inflammatory drugs has never been demonstrated in any wild-type mouse/rat
      model using an mPGES-1 inhibitor. Here we report discovery of a novel type of
      selective mPGES-1 inhibitors potent for both human and mouse mPGES-1 enzymes
      through structure-based rational design. Based on in vivo studies using wild-type
      mice, the lead compound is indeed non-toxic, orally bioavailable, and more potent
      in decreasing the PGE2 (an inflammatory marker) levels compared to the currently
      available drug celecoxib. This is the first demonstration in wild-type mice that
      mPGES-1 is truly a promising target for the next generation of anti-inflammatory
      drugs.

PMID- 29581543
TI  - Programmed cell death ligand-1 expression in tumor and immune cells is associated
      with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal
      melanoma.
AB  - Programmed cell death-1/ligand (PD-1/PD-L1) interaction negatively regulates T
      cell activity. PD-L1 expression in tumor cells, antigen-presenting cells, and
      lymphocytes of the tumor microenvironment is associated with response to
      treatment with PD-1/PD-L1 inhibitors, but there is still debate on the cutoff
      value that correlates with responders. In uveal melanoma (UM), 40% of patients
      will develop liver metastases and, amongst them, 90% will succumb to their
      disease. The aim of this study was to analyze PD-L1 expression as a prognostic
      marker and as a possible therapeutic target for UM. Sixty-seven enucleated eyes
      from UM patients with relevant clinical information were analyzed. Univariate and
      multivariate analysis were used to evaluate association of PD-L1 with survival.
      PD-L1 expression was positive relatively to tumor cells, immune cells, and the
      tumor and tumor-infiltrating immune cell group scoring in 46, 34 and 55% of the
      cases, respectively. On univariate analysis, tumor cells and the tumor and tumor
      infiltrating immune cell group PD-L1 expression was associated with a longer
      metastasis-free survival (P = 0.04 and P = 0.007). However, on multivariate
      analysis, only the tumor and tumor-infiltrating immune cell group positivity was
      associated with longer metastasis-free survival (P = 0.01). Furthermore, tumor
      cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was
      associated with decreased tumor-infiltrating lymphocytes (P = 0.02). PD-L1, when
      expressed in uveal melanoma, is associated with better patient outcome and
      decreased tumor-infiltrating lymphocytes. These results support the consideration
      of anti-PD-1/PD-L1 therapy in uveal melanoma. To determine the best cutoff value,
      further studies from patients enrolled in clinical trials treated with PD-1/PD-L1
      inhibitors are necessary.

PMID- 29581544
TI  - Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell
      lymphomas.
AB  - In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and
      BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines
      subgroups of patients with altered prognosis that has not been evaluated in
      primary cutaneous large B-cell lymphoma. Our objectives were to assess the double
      hit and dual expressor status in a cohort of 44 patients with primary cutaneous
      large B-cell lymphoma according to the histological subtype and to evaluate their
      prognosis relevance. The 44 cases defined by the presence of more than 80% of
      large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre
      lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell
      lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed
      MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n
      = 6 or n = 19, respectively). Only one primary cutaneous follicle centre
      lymphoma, large-cell case had a double-hit status (2%). Specific survival was
      significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type
      than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and
      for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030).
      Both overall survival and specific survival were worse for patients belonging to
      the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type
      subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or
      BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively).
      As the differential diagnosis between primary cutaneous follicle centre lymphoma,
      large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a
      major impact on prognosis, dual-expression of BCL2 and MYC may represent a new
      diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg
      type subtype and further identifies patients with impaired survival. Finally, the
      double-hit assessment does not appear clinically relevant in primary cutaneous
      large B-cell lymphoma.

PMID- 29581545
TI  - Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia
      induction.
AB  - Microglia are highly motile glial cells that are proposed to mediate synaptic
      pruning during neuronal circuit formation. Disruption of signaling between
      microglia and neurons leads to an excess of immature synaptic connections,
      thought to be the result of impaired phagocytosis of synapses by microglia.
      However, until now the direct phagocytosis of synapses by microglia has not been
      reported and fundamental questions remain about the precise synaptic structures
      and phagocytic mechanisms involved. Here we used light sheet fluorescence
      microscopy to follow microglia-synapse interactions in developing organotypic
      hippocampal cultures, complemented by a 3D ultrastructural characterization using
      correlative light and electron microscopy (CLEM). Our findings define a set of
      dynamic microglia-synapse interactions, including the selective partial
      phagocytosis, or trogocytosis (trogo-: nibble), of presynaptic structures and the
      induction of postsynaptic spine head filopodia by microglia. These findings allow
      us to propose a mechanism for the facilitatory role of microglia in synaptic
      circuit remodeling and maturation.

PMID- 29581546
TI  - Depth of organ response in AL amyloidosis is associated with improved survival:
      grading the organ response criteria.
AB  - Organ recovery following anti-plasma cell therapy is associated with improved
      outcome in patients with AL amyloidosis. Current organ response criteria do not
      consider the depth of response. Newly diagnosed AL amyloidosis patients who had
      involvement of at least one evaluable organ and documentation of organ response
      were included. Cardiac response was seen in 182 patients. Time to cardiac
      response was 9.4 months. Renal response was seen in 278 patients, at a median
      time to response of 6 months. Hepatic response was seen in 70 patients, with a
      median time to response of 6.1 months. In all organs, the deeper the organ
      response achieved, the longer the survival. This led to four organ response
      criteria: complete organ response (nadir NT-proBNP <=400 pg/mL; nadir proteinuria
      <=200 mg per 24 h; nadir alkaline phosphatase <=*2 lower limit of normal); very
      good partial organ response (>60% reduction in parameter not meeting complete
      organ response definition); partial organ response (31-60% reduction in
      parameter); and non-responder (<=30% reduction in organ response parameter).
      Cardiac and renal progression were associated with baseline organ impairment and
      inversely associated with the depth of organ response. Grading the depth of organ
      response provides additional valuable prognostic information for newly diagnosed
      AL amyloidosis patients.

PMID- 29581548
TI  - Charge transport in the inverted Marcus region.

PMID- 29581549
TI  - Transition from direct to inverted charge transport Marcus regions in molecular
      junctions via molecular orbital gating.
AB  - Solid-state molecular tunnel junctions are often assumed to operate in the
      Landauer regime, which describes essentially activationless coherent tunnelling
      processes. In solution, on the other hand, charge transfer is described by Marcus
      theory, which accounts for thermally activated processes. In practice, however,
      thermally activated transport phenomena are frequently observed also in solid
      state molecular junctions but remain poorly understood. Here, we show
      experimentally the transition from the Marcus to the inverted Marcus region in a
      solid-state molecular tunnel junction by means of intra-molecular orbital gating
      that can be tuned via the chemical structure of the molecule and applied bias. In
      the inverted Marcus region, charge transport is incoherent, yet virtually
      independent of temperature. Our experimental results fit well to a theoretical
      model that combines Landauer and Marcus theories and may have implications for
      the interpretation of temperature-dependent charge transport measurements in
      molecular junctions.

PMID- 29581547
TI  - Protein targeting chimeric molecules specific for bromodomain and extra-terminal
      motif family proteins are active against pre-clinical models of multiple myeloma.
AB  - Bromodomain and extraterminal (BET) domain containing protein (BRD)-4 modulates
      the expression of oncogenes such as c-myc, and is a promising therapeutic target
      in diverse cancer types. We performed pre-clinical studies in myeloma models with
      bi-functional protein-targeting chimeric molecules (PROTACs) which target BRD4
      and other BET family members for ubiquitination and proteasomal degradation.
      PROTACs potently reduced the viability of myeloma cell lines in a time-dependent
      and concentration-dependent manner associated with G0/G1 arrest, reduced levels
      of CDKs 4 and 6, increased p21 levels, and induction of apoptosis. These agents
      specifically decreased cellular levels of downstream BRD4 targets, including c
      MYC and N-MYC, and a Cereblon-targeting PROTAC showed downstream effects similar
      to those of an immunomodulatory agent. Notably, PROTACs overcame bortezomib,
      dexamethasone, lenalidomide, and pomalidomide resistance, and their activity was
      maintained in otherwise isogenic myeloma cells with wild-type or deleted TP53.
      Combination studies showed synergistic interactions with dexamethasone, BH3
      mimetics, and Akt pathway inhibitors. BET-specific PROTACs induced a rapid loss
      of viability of primary cells from myeloma patients, and delayed growth of MM1.S
      based xenografts. Our data demonstrate that BET degraders have promising activity
      against pre-clinical models of multiple myeloma, and support their translation to
      the clinic for patients with relapsed and/or refractory disease.

PMID- 29581550
TI  - When radionuclides meet nanoparticles.

PMID- 29581551
TI  - Nanoparticles as multimodal photon transducers of ionizing radiation.
AB  - In biomedical imaging, nanoparticles combined with radionuclides that generate
      Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies
      and as activatable probes. In these applications, the nanoparticle is often
      viewed as a carrier inert to ionizing radiation from the radionuclide. However,
      certain phenomena such as enhanced nanoparticle luminescence and generation of
      reactive oxygen species cannot be completely explained by Cerenkov luminescence
      interactions with nanoparticles. Herein, we report methods to examine the
      mechanisms of nanoparticle excitation by radionuclides, including interactions
      with Cerenkov luminescence, beta particles and gamma radiation. We demonstrate
      that beta-scintillation contributes appreciably to excitation and reactivity in
      certain nanoparticle systems, and that excitation by radionuclides of
      nanoparticles composed of large atomic number atoms generates X-rays, enabling
      multiplexed imaging through single photon emission computed tomography. These
      findings demonstrate practical optical imaging and therapy using radionuclides
      with emission energies below the Cerenkov threshold, thereby expanding the list
      of applicable radionuclides.

PMID- 29581552
TI  - Ambipolar Landau levels and strong band-selective carrier interactions in
      monolayer WSe2.
AB  - Monolayers (MLs) of transition-metal dichalcogenides (TMDs) exhibit unusual
      electrical behaviour under magnetic fields due to their intrinsic spin-orbit
      coupling and lack of inversion symmetry1-15. Although recent experiments have
      also identified the critical role of carrier interactions within these
      materials11,15, a complete mapping of the ambipolar Landau level (LL) sequence
      has remained elusive. Here we use single-electron transistors (SETs)16,17 to
      perform LL spectroscopy in ML WSe2, and provide a comprehensive picture of the
      electronic structure of a ML TMD for both electrons and holes. We find that the
      LLs differ notably between the two bands, and follow a unique sequence in the
      valence band (VB) that is dominated by strong Zeeman effects. The Zeeman
      splitting in the VB is several times higher than the cyclotron energy, far
      exceeding the predictions of a single-particle model and, moreover, tunes
      significantly with doping 15 . This implies exceptionally strong many-body
      interactions, and suggests that ML WSe2 can serve as a host for new correlated
      electron phenomena.

PMID- 29581553
TI  - Body mass index, abdominal fatness, and hypertension incidence: a dose-response
      meta-analysis of prospective studies.
AB  - Despite the established relationship of obesity to hypertension, the question as
      to whether there is a linear association between these two morbidities is
      unanswered. To quantitatively evaluate the relationship between obesity and
      hypertension, we carried out a dose-response meta-analysis of studies that looked
      at the relationship of different adiposity measures to hypertension. We searched
      PubMed, Embase, and Web of Science databases for articles published before 27
      June 2017. A random-effects model was used to pool relative risks and 95%
      confidence intervals. Restricted cubic spline analysis was used to model the
      relationship. A total of 59 studies were included. Fifty-seven cohort studies
      with 125,071 incident cases among 830,685 participants were included in the
      analysis of body mass index and hypertension with the summary relative risk for
      per 5-unit increment in body mass index of 1.50 (95% confidence interval: 1.40
      1.59). We found that the risk of hypertension in the body mass index analysis was
      greater in populations where the baseline body mass index was <25 kg/m2. The
      summary relative risk for a 10-cm increase in waist circumference was 1.25 (95%
      confidence interval: 1.19-1.32) and per 0.1-unit increase in waist-to-hip ratio
      was 1.27 (95% confidence interval: 1.18-1.37). This meta-analysis suggests that
      in normal range of obesity indexes, as lean as possible may be the best
      suggestion to prevent hypertension incidence.

PMID- 29581554
TI  - Heart rate reduction decreases central blood pressure in sick sinus syndrome
      patients with a permanent cardiac pacemaker.
AB  - Increased resting heart rate (HR) contributes to higher cardiovascular mortality
      and morbidity in the healthy as well as in people with cardiovascular diseases,
      possibly due to elevated blood pressure (BP) among other mechanisms. Data on the
      relationship between HR and central (aortic) BP remains controversial, however,
      and concerning beta-blockers, it has been proposed that pharmacological HR
      lowering is associated with augmentation of central BP. We aimed to study the
      role of pharmacologically unaffected HR on central BP indices in sick sinus
      syndrome patients with a permanent cardiac pacemaker in the HR range from 40 to
      90 bpm. We included 27 subjects (mean age 65.8 +/- 9.5 years, 12 men) with a dual
      chamber pacemaker implanted due to sick sinus syndrome. We determined central
      hemodynamic indices noninvasively during an atrial pacing mode at low (40 bpm),
      middle (60 bpm), and high (90 bpm) HR levels with an oscillometric cuff-based
      device (Sphygmocor XCEL). There was no difference in central systolic BP at the
      middle versus the high HR level (mean 121.2 +/- 13.0 and 121.2 +/- 12.1 mmHg,
      respectively, P = 0.9), but at the low HR level, it was significantly lower than
      at the middle HR level (mean 117.2 +/- 13.1 and 121.2 +/- 13.0 mmHg, P < 0.01).
      Our acute study provides evidence to suggest that at a HR of <60 bpm, sick sinus
      syndrome patients may have a lower central BP than at a higher HR, despite the
      proposed augmenting effects of low HR on central BP.

PMID- 29581555
TI  - Comparison of various anthropometric indices for the identification of a
      predictor of incident hypertension: the ARIRANG study.
AB  - We compared the predictive capability of weight, waist circumference (WC), waist
      to-height ratio (WHtR), waist-to-hip ratio (WHR), body mass index (BMI), body
      roundness index (BRI), and a body shape index (ABSI) to identify incident
      hypertension, and to determine whether any of these indices may be used as a
      better single predictor of incident hypertension. A total of 1718 participants
      aged 39-72 years were collected  in a longitudinal study. Logistic regression
      models were used to evaluate various anthropometric indices as significant
      predictors of hypertension. During 2.8 years of follow-up, 185 new cases of
      hypertension (10.8%) were reported. The BRI and ABSI were significantly higher in
      the participants who had developed hypertension than in those who had not (4.15
      +/- 1.01 vs. 3.57 +/- 1.03, 0.80 +/- 0.04 vs. 0.78 +/- 0.05; respectively, p <
      0.001). After adjusting for confounding variables, logistic regression analysis
      indicated that participants within the highest quartile of WC and WHtR were 4.79
      and 4.51 times more likely to have hypertension than those within the lowest
      quartile (OR 4.79, 95% CI 2.49-9.20 vs. OR 4.51, 95% CI 2.41-8.43, respectively,
      p < 0.0001); in contrast, no such correlation was found for BMI, WHR, BRI, and
      ABSI. WC (AUC: 0.672) showed a more powerful predictive ability for hypertension
      (p < 0.0001) than BMI (AUC: 0.623), and an equal predictive power for
      hypertension as WHtR (AUC: 0.662) and BRI (AUC: 0.662) in the general population.
      We concluded that WC and/or WHtR but not BMI, showed superior prediction
      capability compared to WHR, BRI, and ABSI, for determining the incidence of
      hypertension in a community-based prospective study.

PMID- 29581556
TI  - Salt sensitivity of blood pressure at age 8 years in children born preterm.
AB  - Preterm birth and low birth weight have been associated with an increased risk of
      hypertension; postnatal growth and dietary salt intake may contribute to these
      associations. In adults, the change of blood pressure (BP) in response to
      modifications in salt intake, i.e., salt sensitivity of BP, has been
      independently associated with cardiovascular disease. Little is known about salt
      sensitivity in children. We hypothesize that it may partly explain the
      association between preterm birth and higher BP in later life. We assessed salt
      sensitivity of BP at age 8 years in 63 preterm-born children, and explored its
      association with postnatal growth, sodium intake, and body composition from
      infancy onwards. BP was measured at baseline and after a 7-day high-salt diet.
      The difference in mean arterial pressure (MAP) was calculated; salt sensitivity
      was defined as an increase in MAP of >=5%. Ten children (16%) showed salt
      sensitivity of BP, which was associated with neonatal growth restriction as well
      as with lower fat mass and BMI from infancy onwards. At age 8 years, children
      classified as salt sensitive had a lower weight-for-age SD-score (-1.5 +/- 1.3
      vs. -0.6 +/- 1.1) and BMI (13.8 +/- 1.7 vs. 15.5 +/- 1.8 kg/m2) compared to their
      salt resistant counterparts. Sodium intake was not associated with (salt
      sensitivity of) BP. Salt sensitivity of BP was demonstrated in preterm-born
      children at age 8 years and may contribute to the development of cardiovascular
      disease at later age. Long-term follow-up studies are necessary to assess
      reproducibility of our findings and to explore clustering with other
      cardiovascular risk factors.

PMID- 29581557
TI  - Less primary fistula failure in hypertensive patients.
AB  - End stage renal disease (ESRD) patients suffer from advanced renal diseases and
      actually nonfunctioning kidneys, and need kidney transplantation or dialysis.
      Hemodialysis (HD) is the most used method and requires a vascular access (VA).
      Arteriovenous fistula (AVF) is the first choice of VA over the world for having
      least morbidity and mortality. Despite the wide-spread use of AVFs, the rate of
      AVF failures are notable. Detecting the factors that cause AVF failure can reduce
      repeating VA surgeries and hospitalization of ESRD patients. Present research
      studies 480 Iranian HD patients who underwent AVF surgery from 2010 to 2017 and
      aged 18-90 years old, using data mining techniques. (i) The AVF failure rate was
      equal to 8.96%, such that AVF failure has occurred in 3.54% and 5.52% of HD
      patient with and without hypertension, respectively. (ii) The rate of non-failure
      AVF in hypertensive patients is 61.46%, whereas the same rate for patients with
      negative history of hypertension reaches to 29.58%. (iii) Hypertension has a
      significant inverse association with AVF failure (Spearman's rho = -0.160, P
      value <= 0.005). (iv) The decision tree (with accuracy rate = 92.24%) shows less
      AVF failure in hypertsensive patients (5.53%) comparing with non-hypertensive
      patients (15.09%). (v) The AVFs with greater failure rates and non-hypertensive
      HD patients were clustered together. "Significantly lower risk of AVF failure was
      associated with presence of a positive history of hypertension; in other words,
      positive history of hypertension has an adverse effect on AVF failure and
      Hypertensive HD patients have more maturated AVF."

PMID- 29581558
TI  - Identification of Urinary Activin A as a Novel Biomarker Reflecting the Severity
      of Acute Kidney Injury.
AB  - Acute kidney injury (AKI) is a common but complex condition that is associated
      with increased morbidity and mortality. In the present study, we examined whether
      urinary activin A, a member of the TGF-beta superfamily, is present in mice with
      ischemia-reperfusion injury and in humans with AKI, as well as its potential as a
      biomarker for AKI. Expression of activin A was markedly increased in ischemic
      mouse kidneys. In situ hybridization demonstrated that activin mRNA was expressed
      in tubular cells of ischemic kidneys but not of normal kidneys. Immunoreactive
      activin A, which was absent in normal kidneys, was detected in the cytoplasm of
      proximal tubular cells in ischemic kidneys. Activin A was undetectable in the
      urine of normal mice. In contrast, activin A was significantly increased in the
      urine of ischemic mice at 3 h after reperfusion. Urinary activin A levels
      increased according to the period of ischemia. In humans, urinary activin A was
      almost undetectable in healthy volunteers and in patients with pre-renal AKI, but
      was significantly increased in patients with renal AKI. There was no significant
      correlation between urinary activin A and serum activin A. Collectively, urinary
      activin A might be a useful biomarker reflecting the severity of AKI.

PMID- 29581559
TI  - Improvement of physical properties of calcium phosphate cement by elastin-like
      polypeptide supplementation.
AB  - Calcium phosphate cements (CPCs) are synthetic bioactive cements widely used as
      hard tissue substitutes. Critical limitations of use include their poor
      mechanical properties and poor anti-washout behaviour. To address those
      limitations, we combined CPC with genetically engineered elastin-like
      polypeptides (ELPs). We investigated the effect of the ELPs on the physical
      properties and biocompatibility of CPC by testing ELP/CPC composites with various
      liquid/powder ratios. Our results show that the addition of ELPs improved the
      mechanical properties of the CPC, including the microhardness, compressive
      strength, and washout resistance. The biocompatibility of ELP/CPC composites was
      also comparable to that of the CPC alone. However, supplementing CPC with ELPs
      functionalized with octaglutamate as a hydroxyapatite binding peptide increased
      the setting time of the cement. With further design and modification of our
      biomolecules and composites, our research will lead to products with diverse
      applications in biology and medicine.

PMID- 29581560
TI  - Surface enhanced Raman spectroscopy of Chlamydia trachomatis and Neisseria
      gonorrhoeae for diagnostics, and extra-cellular metabolomics and biochemical
      monitoring.
AB  - SERS spectra excited at 785 nm of the bacteria Chlamydia trahomatis (elementary
      bodies, EB) and Neisseria gonorrheoae, the causative pathogens for the two most
      common sexually transmitted diseases (STD), chlamydia and gonorrhea,
      respectively, are reported. Although both are Gram-negative bacteria, the SERS
      signatures of C. trachomatis and N. gonorrheoae are completely different. N.
      gonorrheoae SERS spectra are due to the starvation induced nucleotide metabolites
      adenine and guanine, and the surface associated co-enzyme nicotinamide adenine
      dinucleotide and are very similar on Au and Ag although the spectrum appears more
      rapidly on Ag. The C. trachomatis SERS spectrum is dominated by the vibrational
      features of cell surface proteins. While features attributable to specific
      residues and the amide backbone characterize the C. trachomatis spectrum on Ag,
      the corresponding SERS spectrum on Au substrates displays vibrational
      characteristics of aggregated proteins. The prospects for the development of a
      SERS based platform for rapid (<one hour), low-cost bacterial STD diagnostics are
      promising based on these initial studies. Furthermore, this biomedical
      application demonstrates the potential for SERS to be a sensitive real time probe
      of the dynamics of biochemical activity in the cell wall and extracellular
      regions of microorganisms.

PMID- 29581561
TI  - Nutritional risk assessment at admission can predict subsequent muscle loss in
      critically ill patients.
AB  - Muscle loss in critically ill patients may be related to nutrition. We study the
      association between modified NUTrition RIsk in the Critically ill (mNUTRIC) score
      obtained at admission to intensive care unit (ICU) and subsequent muscle loss. We
      measured rectus femoris cross-sectional area (RFCSA) by ultrasound on days 1, 3,
      7, and 10 of ICU admission. We used linear mixed effects model following natural
      logarithmic transformation of the data. Forty-eight patients (median (IQR) age 66
      (55-72.5) years, 71% male, APACHE II score 31 (25-34), BMI 24.2 (21.5-27.1)
      kg/m2) were analyzed. The high mNUTRIC score (>5) cohort (n = 35) lost
      significantly more muscle as compared to the low (<=5) group (n = 13); the
      adjusted ratio (high versus low group) of the geometric mean RFCSA were (0.58,
      95% CI 0.46-0.75) for right and (0.61, 95% CI 0.49-0.77) for left, both p <
      0.001. mNUTRIC score obtained at admission to ICU can identify patients at risk
      of subsequent muscle loss.

PMID- 29581562
TI  - When foods contain both a gluten-free claim and an allergen advisory statement
      for wheat: should consumers be concerned?

PMID- 29581563
TI  - A review of probiotic supplementation in healthy adults: helpful or hype?
AB  - Probiotic supplements have a positive impact on several health outcomes. However,
      the majority of published studies have focused on populations with specific
      health pathologies. Therefore, this study reviewed the current literature on the
      health effects of probiotic consumption in "healthy adults." The findings from
      this review may help guide consumers, researchers, and manufacturers regarding
      probiotic supplementation. Relevant literature published between 1990 and August
      2017 was reviewed. Studies were included if they were experimental trials,
      included healthy adults, used live bacteria, and had accessible full-text
      articles published in English. Included studies were classified according to
      common foci that emerged. Forty-five studies were included in this review. Five
      foci emerged: gut microbiota changes (n = 15); immune system response (n = 16);
      lipid profile and cardiovascular disease risk (n = 14); gastrointestinal
      discomfort (n = 11); and female reproductive health (n = 4). Results suggest that
      probiotic supplementation in healthy adults can lead to transient improvement in
      gut microbiota concentration of supplement-specific bacteria. Evidence also
      supports the role of probiotics in improving immune system responses, stool
      consistency, bowel movement, and vaginal lactobacilli concentration. There is
      insufficient evidence to support the role of probiotics to improve blood lipid
      profile. Probiotic consumption can improve in the immune, gastrointestinal, and
      female reproductive health systems in healthy adults. However, this review failed
      to support the ability of probiotics to cause persistent changes in gut
      microbiota, or improve lipid profile in healthy adults. The feasibility of
      probiotics consumption to provide benefits in healthy adults requires further
      investigation.

PMID- 29581564
TI  - Prognostic impact of early nutritional support in patients affected by locally
      advanced and metastatic pancreatic ductal adenocarcinoma undergoing chemotherapy.
AB  - BACKGROUND/OBJECTIVES: The aim of this analysis was to determine the risk of
      malnutrition and the prognostic value of nutritional intervention in patients
      affected by pancreatic ductal adenocarcinoma (PDAC) undergoing chemotherapy.
      SUBJECTS/METHODS: Clinical-pathological and nutritional data were correlated with
      overall survival (OS) using a Cox model. Nutritional status was determined by
      Malnutrition Universal Screening Tool (MUST), body mass index, weight loss in the
      past 6 months, presence of nutrition-related symptoms, and current energy intake.
      Nutritional intervention included appropriate individual dietary counseling.
      RESULTS: Data from 109 patients were gathered (median age 63 years). The majority
      of patients (64.2%) presented a MUST value of >= 2, corresponding to a high risk
      of malnutrition. At multivariate analysis for OS in locally advanced and
      metastatic PDAC patients, the time between the diagnosis and the nutritional
      intervention (HR 2.22, p = 0.017), the performance status (HR 1.38, p = 0.075),
      the surgery of the primary (HR 5.89, p = 0.005), and the response to the first
      line (HR 5.9, p = 0.03) were independent significant predictors of outcome.
      Furthermore, a weight gain > 2% from the baseline weight was correlated with the
      time between the diagnosis and the nutritional intervention (p = 0.021): in
      patients receiving a nutritional support within 3 months from diagnosis, a 2%
      weight gain was associated with a 2-year OS benefit (50.3% vs. 33.0%, p = 0.04).
      CONCLUSIONS: This analysis suggests that the early nutritional support may
      contribute to influence the prognosis of patients affected by advanced PDAC
      undergoing chemotherapy.

PMID- 29581565
TI  - ARE-mediated decay controls gene expression and cellular metabolism upon oxygen
      variations.
AB  - Hypoxia triggers profound modifications of cellular transcriptional programs.
      Upon reoxygenation, cells return to a normoxic gene expression pattern and mRNA
      produced during the hypoxic phase are degraded. TIS11 proteins control
      deadenylation and decay of transcripts containing AU-rich elements (AREs). We
      observed that the level of dTIS11 is decreased in hypoxic S2 Drosophila cells and
      returns to normal level upon reoxygenation. Bioinformatic analyses using the ARE
      assessing algorithm AREScore show that the hypoxic S2 transcriptome is enriched
      in ARE-containing transcripts and that this trend is conserved in human myeloid
      cells. Moreover, an efficient down-regulation of Drosophila ARE-containing
      transcripts during hypoxia/normoxia transition requires dtis11 expression.
      Several of these genes encode proteins with metabolic functions. Here, we show
      that ImpL3 coding for Lactate Dehydrogenase in Drosophila, is regulated by ARE
      mediated decay (AMD) with dTIS11 contributing to ImpL3 rapid down-regulation upon
      return to normal oxygen levels after hypoxia. More generally, we observed that
      dtis11 expression contributes to cell metabolic and proliferative recovery upon
      reoxygenation. Altogether, our data demonstrate that AMD plays an important role
      in the control of gene expression upon variation in oxygen concentration and
      contributes to optimal metabolic adaptation to oxygen variations.

PMID- 29581566
TI  - Correction to: Halistanol sulfates I and J, new SIRT1-3 inhibitory steroid
      sulfates from a marine sponge of the genus Halichondria.
AB  - The original article can be found online at https://doi.org/10.1038/ja.2017.145 .

PMID- 29581567
TI  - Gating interaction maps reveal a noncanonical electromechanical coupling mode in
      the Shaker K+ channel.
AB  - Membrane potential regulates the activity of voltage-dependent ion channels via
      specialized voltage-sensing modules, but the mechanisms involved in coupling
      voltage-sensor movement to pore opening remain unclear owing to a lack of resting
      state structures and robust methods to identify allosteric pathways. Here, using
      a newly developed interaction-energy analysis, we probe the interfaces of the
      voltage-sensing and pore modules in the Drosophila Shaker K+ channel. Our
      measurements reveal unexpectedly strong equilibrium gating interactions between
      contacts at the S4 and S5 helices in addition to those between S6 and the S4-S5
      linker. Network analysis of MD trajectories shows that the voltage-sensor and
      pore motions are linked by two distinct pathways: a canonical pathway through the
      S4-S5 linker and a hitherto unknown pathway akin to rack-and-pinion coupling
      involving the S4 and S5 helices. Our findings highlight the central role of the
      S5 helix in electromechanical transduction in the voltage-gated ion channel
      (VGIC) superfamily.

PMID- 29581569
TI  - Prostate MRI can be accurate but can variability be reduced?

PMID- 29581568
TI  - Author Correction: Global delay in nascent strand DNA methylation.
AB  - Following online publication of this article, the Gene Expression Omnibus records
      corresponding to accession codes GSM2406773, MN-d6, and GSM2406772, MN-d14,
      listed in the data availability statement were deleted. The data are now
      available under accession codes GSM3039355, WGBS_hESC_WT_D6_R4 (MN day 6), and
      GSM3039351, WGBS_hESC_WT_D14_R4 (MN day 14), and the data availability statement
      has been updated with the new accession codes in the HTML and PDF versions of the
      article.

PMID- 29581570
TI  - Two methods of prediction signatures.

PMID- 29581571
TI  - Prostate cancer: Solo PSA test does not lower mortality.

PMID- 29581572
TI  - Multilevel robustness.

PMID- 29581573
TI  - All-organic superhydrophobic coatings with mechanochemical robustness and liquid
      impalement resistance.
AB  - Superhydrophobicity is a remarkable evolutionary adaption manifested by several
      natural surfaces. Artificial superhydrophobic coatings with good mechanical
      robustness, substrate adhesion and chemical robustness have been achieved
      separately. However, a simultaneous demonstration of these features along with
      resistance to liquid impalement via high-speed drop/jet impact is challenging.
      Here, we describe all-organic, flexible superhydrophobic nanocomposite coatings
      that demonstrate strong mechanical robustness under cyclic tape peels and Taber
      abrasion, sustain exposure to highly corrosive media, namely aqua regia and
      sodium hydroxide solutions, and can be applied to surfaces through scalable
      techniques such as spraying and brushing. In addition, the mechanical flexibility
      of our coatings enables impalement resistance to high-speed drops and turbulent
      jets at least up to ~35 m s-1 and a Weber number of ~43,000. With multifaceted
      robustness and scalability, these coatings should find potential usage in harsh
      chemical engineering as well as infrastructure, transport vehicles and
      communication equipment.

PMID- 29581574
TI  - Engineering smart antibodies.

PMID- 29581575
TI  - Chain reaction.

PMID- 29581576
TI  - Trump's materials world.

PMID- 29581577
TI  - The effective way.

PMID- 29581578
TI  - Heparin-binding epidermal growth factor contributes to COPD disease severity by
      modulating airway fibrosis and pulmonary epithelial-mesenchymal transition.
AB  - Although airway fibrosis and epithelial-mesenchymal transition (EMT) contribute
      to airway remodeling in chronic obstructive pulmonary disease (COPD), the
      mechanisms underlying their development have not been fully elucidated. In the
      present study, we aimed to assess heparin-binding epidermal growth factor (HB
      EGF) expression in the airways of patients with COPD and to elucidate the
      possible role of HB-EGF in the pathology of COPD. Sputum and lung tissue HB-EGF
      expression was evaluated in control subjects and patients with COPD. The
      relationships between HB-EGF expression, disease severity, collagen deposition
      (fibrosis), and EMT were investigated. In vitro, human bronchial epithelial (HBE)
      cells and lung fibroblast cells exposed to the recombinant HB-EGF, collagen
      deposition and EMT were assessed. We found that sputum HB-EGF expression was
      significantly increased in patients with COPD compared with non-smokers and
      smokers without COPD. There was a significant positive correlation between sputum
      HB-EGF and COPD assessment test (CAT) score. HB-EGF expression was significantly
      increased in the lung tissue samples of patients with COPD and associated with
      collagen deposition and N- and E-cadherin, and vimentin expression. In vitro, HB
      EGF promoted collagen production in lung fibroblasts. Moreover, HB-EGF induced
      the EMT process through induction of N-and E-cadherin, and vimentin expression in
      HBE cells. Collectively, HB-EGF induces airway remodeling by modulating airway
      fibrosis and pulmonary EMT, and contributes to the COPD severity. The current
      data may provide insight into the underlying pathogenesis of COPD, in which HB
      EGF has an important pathogenic role.

PMID- 29581579
TI  - Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute
      kidney injury by attenuating inflammation and programmed cell death.
AB  - E-cadherin is a major component of tubular adherent proteins that maintain
      intercellular contacts and cell polarity in epithelial tissue. It is involved in
      pathological processes of renal cell carcinoma and fibrotic diseases via
      epithelial-mesenchymal transition. Although studies have shown E-cadherin is
      significantly downregulated in acute kidney injury (AKI), its function in AKI is
      unknown. Here, we evaluated cell damage and inflammation in cisplatin-stimulated
      tubular epithelial cell lines after disrupting E-cadherin and restoring it with
      PPBICA, a small molecule identified by high-throughput screening. We also
      determined the therapeutic potential of restoring E-cadherin in vivo. Results
      show cisplatin reduced E-cadherin expression both in mouse kidney and proximal
      tubular epithelial cell lines (mTECs). PPBICA restored E-cadherin levels, which
      increased cell viability while attenuating programmed cell death. This may be
      mediated via deactivation of the RIPK1/RIPK3 axis and decreased caspase3
      cleavage. In addition, PPBICA suppressed inflammatory response in cisplatin
      treated mTECs, which correlated with suppressed NF-kappaB phosphorylation and
      promoter activity. In contrast, disruption of E-cadherin promoted cell damage and
      inflammation. PPBICA failed to further attenuate kidney damage in E-cadherin
      knockdown cells, indicating that PPBICA protects against mTECs through E-cadherin
      restoration. We also found that peritoneal injection of PPBICA in mice prevented
      loss of renal function and tubular damage by suppressing NF-kappaB-driven renal
      inflammation and RIPK-regulated programmed cell death. This was driven by
      restoration of E-cadherin in cisplatin nephropathy. Additionally, PPBICA
      attenuated cisplatin-induced kidney damage in an established AKI model,
      indicating its therapeutic potential in the treatment of AKI. In conclusion, E
      cadherin plays functional roles in tubule integrity, programmed cell death, and
      renal inflammation. Our results underscore the potential of E-cadherin
      restoration as a novel therapeutic strategy for AKI.

PMID- 29581580
TI  - Reduced expression of the H19 long non-coding RNA inhibits pancreatic cancer
      metastasis.
AB  - H19 is an oncofetal RNA expressed in the developing embryo as well as in bladder,
      breast, gastric, pancreatic, hepatocellular, and prostate cancers. Recent studies
      have shown that H19 enhances cancer invasion and metastasis; however, its roles
      in cancer remain controversial. In the current study, H19 exhibited the second
      largest increase (82.4-fold) and represented the only non-protein coding gene
      among 11 genes identified that were elevated over 10-fold in lung-metastasis
      derived pancreatic cancer cells compared with their parental cells using a mouse
      metastatic model. Subsequently, we further clarified the roles of H19 in
      pancreatic cancer growth and metastasis using in vitro and in vivo techniques. In
      situ hybridization showed that H19 was detected in 23 of 139 invasive ductal
      carcinomas (17%), and that H19 expression positively correlated with higher
      histological grades (P < 0.0001). Overexpression of H19 in PANC-1 pancreatic
      cancer cells induced higher motilities, whereas H19 inhibition using shRNA and
      siRNA showed opposite results; however, cell growth rates were not impacted.
      Intravenous injection of H19 shRNA vector-transfected PANC-1 cells yielded marked
      inhibition of metastasis in the liver and lungs of immunodeficient mice. These
      findings suggest that H19 has important roles in pancreatic cancer metastasis,
      and that inhibition of H19 represents a novel candidate for pancreatic cancer
      therapy.

PMID- 29581581
TI  - Stage-Rocked Electron Channeling for Crystal Orientation Mapping.
AB  - Microstructural analysis by crystal orientation mapping of bulk functional
      materials is an essential and routine operation in the engineering of material
      properties. Far and away the most successfully employed technique, Electron
      Backscattered Diffraction (EBSD), provides high spatial resolution information at
      the cost of limited angular resolution and a distorted imaging condition. In this
      work, we demonstrate a stage-rocked electron channeling approach as a low-cost
      orientation mapping alternative to EBSD. This is accomplished by automated
      electron channeling contrast imaging (ECCI) as the microscope stage physically
      tilts/rotates a sample through a reduced hemisphere of orientations followed by
      computational reconstruction of electron channeling patterns (ECP). Referred to
      as Orientation Mapping by Electron Channeling (OMEC), our method offers
      advantages in terms of local defect analysis, as it combines the advantages of
      selected area ECP (SACP) and ECCI. We also illustrate dynamic or "adaptive"
      sampling schemes to increase the throughput of the technique. Finally, we discuss
      the implications for sample analysis in which large 3D maps of ECCI images can be
      routinely constructed of challenging crystalline samples. As an electron
      channeling-based approach to orientation mapping, OMEC may open new routes to
      characterize crystalline materials with high angular and spatial resolution.

PMID- 29581583
TI  - TAGing for destruction.

PMID- 29581582
TI  - Unfolding of a ClC chloride transporter retains memory of its evolutionary
      history.
AB  - ClC chloride channels and transporters are important for chloride homeostasis in
      species from bacteria to human. Mutations in ClC proteins cause genetically
      inherited diseases, some of which are likely to involve folding defects. The ClC
      proteins present a challenging and unusual biological folding problem because
      they are large membrane proteins possessing a complex architecture, with many
      reentrant helices that go only partway through membrane and loop back out. Here
      we were able to examine the unfolding of the Escherichia coli ClC transporter,
      ClC-ec1, using single-molecule forced unfolding methods. We found that the
      protein could be separated into two stable halves that unfolded independently.
      The independence of the two domains is consistent with an evolutionary model in
      which the two halves arose from independently folding subunits that later fused
      together. Maintaining smaller folding domains of lesser complexity within large
      membrane proteins may be an advantageous strategy to avoid misfolding traps.

PMID- 29581584
TI  - Biosynthesis of redox-active metabolites in response to iron deficiency in
      plants.
AB  - Iron is an essential but poorly bioavailable nutrient because of its low
      solubility, especially in alkaline soils. Here, we describe the discovery of a
      previously undescribed redox-active catecholic metabolite, termed sideretin,
      which derives from the coumarin fraxetin and is the primary molecule exuded by
      Arabidopsis thaliana roots in response to iron deficiency. We identified two
      enzymes that complete the biosynthetic pathway of fraxetin and sideretin.
      Chemical characterization of fraxetin and sideretin, and biological assays with
      pathway mutants, suggest that these coumarins are critical for iron nutrition in
      A. thaliana. Further, we show that sideretin production also occurs in eudicot
      species only distantly related to A. thaliana. Untargeted metabolomics of the
      root exudates of various eudicots revealed production of structurally diverse
      redox-active molecules in response to iron deficiency. Our results indicate that
      secretion of small-molecule reductants by roots may be a widespread and
      previously underappreciated component of reduction-based iron uptake.

PMID- 29581585
TI  - The dTAG system for immediate and target-specific protein degradation.
AB  - Dissection of complex biological systems requires target-specific control of the
      function or abundance of proteins. Genetic perturbations are limited by off
      target effects, multicomponent complexity, and irreversibility. Most limiting is
      the requisite delay between modulation to experimental measurement. To enable the
      immediate and selective control of single protein abundance, we created a
      chemical biology system that leverages the potency of cell-permeable
      heterobifunctional degraders. The dTAG system pairs a novel degrader of
      FKBP12F36V with expression of FKBP12F36V in-frame with a protein of interest. By
      transgene expression or CRISPR-mediated locus-specific knock-in, we exemplify a
      generalizable strategy to study the immediate consequence of protein loss. Using
      dTAG, we observe an unexpected superior antiproliferative effect of pan-BET
      bromodomain degradation over selective BRD4 degradation, characterize immediate
      effects of KRASG12V loss on proteomic signaling, and demonstrate rapid
      degradation in vivo. This technology platform will confer kinetic resolution to
      biological investigation and provide target validation in the context of drug
      discovery.

PMID- 29581586
TI  - Altered access to beneficial mutations slows adaptation and biases fixed
      mutations in diploids.
AB  - Ploidy varies considerably in nature. However, our understanding of the impact of
      ploidy on adaptation is incomplete. Many microbial evolution experiments
      characterize adaptation in haploid organisms, but few focus on diploid organisms.
      Here, we perform a 4,000-generation evolution experiment using diploid strains of
      the yeast Saccharomyces cerevisiae. We show that the rate of adaptation and
      spectrum of beneficial mutations are influenced by ploidy. Haldane's sieve
      effectively alters access to recessive beneficial mutations in diploid
      populations, leading to a slower rate of adaptation and a spectrum of beneficial
      mutations that is shifted towards dominant mutations. Genomic position also has
      an important role, as the prevalence of homozygous mutations is largely dependent
      on their proximity to a recombination hotspot. Our results demonstrate key
      aspects of diploid adaptation that have previously been understudied and provide
      support for several proposed theories.

PMID- 29581587
TI  - A biodiversity-crisis hierarchy to evaluate and refine conservation indicators.
AB  - The Convention on Biological Diversity and its Strategic Plan for Biodiversity
      2011-2020 form the central pillar of the world's conservation commitment, with
      196 signatory nations; yet its capacity to reign in catastrophic biodiversity
      loss has proved inadequate. Indicators suggest that few of the Convention on
      Biological Diversity's Aichi targets that aim to reduce biodiversity loss will be
      met by 2020. While the indicators have been criticized for only partially
      representing the targets, a bigger problem is that the indicators do not
      adequately draw attention to and measure all of the drivers of the biodiversity
      crisis. Here, we show that many key drivers of biodiversity loss are either
      poorly evaluated or entirely lacking indicators. We use a biodiversity-crisis
      hierarchy as a conceptual model linking drivers of change to biodiversity loss to
      evaluate the scope of current indicators. We find major gaps related to
      monitoring governments, human population size, corruption and threat-industries.
      We recommend the hierarchy is used to develop an expanded set of indicators that
      comprehensively monitor the human behaviour and institutions that drive
      biodiversity loss and that, so far, have impeded progress towards achieving
      global biodiversity targets.

PMID- 29581588
TI  - The interplay of past diversification and evolutionary isolation with present
      imperilment across the amphibian tree of life.
AB  - Human activities continue to erode the tree of life, requiring us to prioritize
      research and conservation. Amphibians represent key victims and bellwethers of
      global change, and the need for action to conserve them is drastically outpacing
      knowledge. We provide a phylogeny incorporating nearly all extant amphibians
      (7,238 species). Current amphibian diversity is composed of both older,
      depauperate lineages and extensive, more recent tropical radiations found in
      select clades. Frog and salamander diversification increased strongly after the
      Cretaceous-Palaeogene boundary, preceded by a potential mass-extinction event in
      salamanders. Diversification rates of subterranean caecilians varied little over
      time. Biogeographically, the Afro- and Neotropics harbour a particularly high
      proportion of Gondwanan relicts, comprising species with high evolutionary
      distinctiveness (ED). These high-ED species represent a large portion of the
      branches in the present tree: around 28% of all phylogenetic diversity comes from
      species in the top 10% of ED. The association between ED and imperilment is weak,
      but many species with high ED are now imperilled or lack formal threat status,
      suggesting opportunities for integrating evolutionary position and phylogenetic
      heritage in addressing the current extinction crisis. By providing a phylogenetic
      estimate for extant amphibians and identifying their threats and ED, we offer a
      preliminary basis for a quantitatively informed global approach to conserving the
      amphibian tree of life.

PMID- 29581589
TI  - The resilience of postglacial hunter-gatherers to abrupt climate change.
AB  - Understanding the resilience of early societies to climate change is an essential
      part of exploring the environmental sensitivity of human populations. There is
      significant interest in the role of abrupt climate events as a driver of early
      Holocene human activity, but there are very few well-dated records directly
      compared with local climate archives. Here, we present evidence from the
      internationally important Mesolithic site of Star Carr showing occupation during
      the early Holocene, which is directly compared with a high-resolution
      palaeoclimate record from neighbouring lake beds. We show that-once established
      there was intensive human activity at the site for several hundred years when the
      community was subject to multiple, severe, abrupt climate events that impacted
      air temperatures, the landscape and the ecosystem of the region. However, these
      results show that occupation and activity at the site persisted regardless of the
      environmental stresses experienced by this society. The Star Carr population
      displayed a high level of resilience to climate change, suggesting that
      postglacial populations were not necessarily held hostage to the flickering
      switch of climate change. Instead, we show that local, intrinsic changes in the
      wetland environment were more significant in determining human activity than the
      large-scale abrupt early Holocene climate events.

PMID- 29581590
TI  - Restoration science does not need redefinition.

PMID- 29581591
TI  - A guide to ancient protein studies.
AB  - Palaeoproteomics is an emerging neologism used to describe the application of
      mass spectrometry-based approaches to the study of ancient proteomes. As with
      palaeogenomics (the study of ancient DNA), it intersects evolutionary biology,
      archaeology and anthropology, with applications ranging from the phylogenetic
      reconstruction of extinct species to the investigation of past human diets and
      ancient diseases. However, there is no explicit consensus at present regarding
      standards for data reporting, data validation measures or the use of suitable
      contamination controls in ancient protein studies. Additionally, in contrast to
      the ancient DNA community, no consolidated guidelines have been proposed by which
      researchers, reviewers and editors can evaluate palaeoproteomics data, in part
      due to the novelty of the field. Here we present a series of precautions and
      standards for ancient protein research that can be implemented at each stage of
      analysis, from sample selection to data interpretation. These guidelines are not
      intended to impose a narrow or rigid list of authentication criteria, but rather
      to support good practices in the field and to ensure the generation of robust,
      reproducible results. As the field grows and methodologies change, so too will
      best practices. It is therefore essential that researchers continue to provide
      necessary details on how data were generated and authenticated so that the
      results can be independently and effectively evaluated. We hope that these
      proposed standards of practice will help to provide a firm foundation for the
      establishment of palaeoproteomics as a viable and powerful tool for
      archaeologists, anthropologists and evolutionary biologists.

PMID- 29581592
TI  - Passively Driven Probe Based on Miniaturized Propeller for Intravascular Optical
      Coherence Tomography.
AB  - Optical coherent tomography (OCT) has enabled clinical applications ranging from
      ophthalmology to cardiology that revolutionized in vivo medical diagnostics in
      the last few decades, and a variety of endoscopic probes have been developed in
      order to meet the needs of various endoscopic OCT imaging. We propose a passive
      driven intravascular optical coherent tomography (IV-OCT) probe in this paper.
      Instead of using any electrically driven scanning device, the probe makes use of
      the kinetic energy of the fluid that flushes away the blood during the
      intravascular optical coherence tomography imaging. The probe converts it into
      the rotational kinetic energy of the propeller, and the rotation of the
      rectangular prism mounted on the propeller shaft enables the scanning of the
      beam. The probe is low cost, and enables unobstructed stable circumferential
      scanning over 360 deg. The experimental results show that the probe scanning
      speed can exceed 100 rotations per second (rps). Spectral-domain OCT imaging of a
      phantom and porcine cardiac artery are demonstrated with axial resolution of 13.6
      MUm, lateral resolution of 22 MUm, and sensitivity of 101.7 dB. We present
      technically the passively driven IV-OCT probe in full detail and discuss how to
      optimize the probe in further.

PMID- 29581594
TI  - Comparison of ultrasound with hysteroscopic and histological findings for
      intrauterine assessment.
AB  - INTRODUCTION: Hysteroscopy with biopsy is a common diagnostic and therapeutic
      method in gynaecology. Its use is preceded by ultrasound examination. The success
      rate of predicting intrauterine findings based on ultrasound has not been
      assessed in the Czech Republic for a long time. In the meantime, there have been
      technological improvements in ultrasound devices. METHOD: Patients indicated for
      hysteroscopy underwent ultrasound examination and their medical history was
      recorded. The percentage agreement between ultrasound and histopathological
      findings was assessed. The secondary goal was to find an easier way of describing
      ultrasound findings in gynaecological practice. RESULTS: The study comprised 255
      patients. In 15 cases, endometrial carcinoma was confirmed by hysteroscopy and
      histopathological examination. Of these, malignancies were suspected based on
      previous ultrasound scans in 11 patients. In 95 cases, intrauterine polyps were
      detected. The success rate for predicting polyps by ultrasound examination was
      65.1%. The agreement between ultrasound and hysteroscopic/histopathological
      findings was 72%. The secondary goal of making the description of the uterine
      cavity easier was not fulfilled. The prediction percentages for the criteria were
      low. The incidence of pathological findings in ultrasound findings labelled as
      anechogenic was 4.8%, suggesting a high negative predictive value. CONCLUSION: In
      spite of the better resolution of new ultrasound devices, their predictive value
      remains limited. Findings that are suspicious in ultrasound should be confirmed
      by hysteroscopy with biopsy.

PMID- 29581593
TI  - L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment
      of RNF8 and RNF168 after DNA damage.
AB  - Cells respond to cytotoxic DNA double-strand breaks (DSBs) by recruiting DNA
      repair proteins to the damaged site. This recruitment is dependent on
      ubiquitylation of adjacent chromatin areas by E3 ubiquitin ligases such as RNF8
      and RNF168, which are recruited sequentially to the DSBs. However, it is unclear
      what dictates the sequential order and recruits RNF168 to the DNA lesion. Here,
      we reveal that L3MBTL2 (lethal(3)malignant brain tumour-like protein 2) is the
      missing link between RNF8 and RNF168. We found that L3MBTL2 is recruited by MDC1
      and subsequently ubiquitylated by RNF8. Ubiquitylated L3MBTL2, in turn,
      facilitates recruitment of RNF168 to the DNA lesion and promotes DNA DSB repair.
      These results identify L3MBTL2 as a key target of RNF8 following DNA damage and
      demonstrates how the DNA damage response pathway is orchestrated by ubiquitin
      signalling.

PMID- 29581595
TI  - Elevated DNA methylation in malignant tumors of the sinonasal tract and its
      association with patient survival.
AB  - BACKGROUND: Epigenetic modifications have been recognized as an important
      mechanism underlying carcinoma progression. DNA methylation plays an important
      role in cancer biology and represents potentially heritable changes in gene
      expression that do not involve DNA sequence. The aim of this study was to
      investigate promoter methylation of selected genes in sinonasal carcinoma by
      comparison with noncancerous sinonasal tissue. METHODS: To search for epigenetic
      events (methylation in 25 tumor suppressor genes) we used MS-MLPA (Methylation
      specific multiplex ligation-dependent probe amplification) to compare methylation
      status of 59 formalin fixed, paraffin embedded tissue samples of sinonasal
      carcinomas with 18 control samples. The most important changes in methylation
      were confirmed using MSP (Methylation specific PCR). Detected alterations in
      methylation were compared with clinicopathological characteristics. RESULTS:
      Using a 20% cut-off for methylation (MS-MLPA), we found significantly higher
      methylation in GATA5 (P=0.0005), THSB1 (P=0.0002) and PAX5 (P=0.03) genes in the
      sinonasal cancer group compared to the control group. Methylation in five or more
      genes was associated with impaired overall survival (P=0.017). CONCLUSION: These
      findings provide evidence that alterations in methylation profile may be one of
      the major mechanisms in sinonasal carcinogenesis. In addition, changes in
      methylation could potentially be used as prognostic factors of sinonasal
      carcinoma and may have implications for future individualized therapy based on
      epigenetic changes.

PMID- 29581596
TI  - Why Is Burnout a Taboo?

PMID- 29581597
TI  - Stability of 2 mg/mL Adenosine Solution in Polyvinyl Chloride and Polyolefin
      Infusion Bags.
AB  - Adenosine is a potent endogenous mediator of vasodilation. Compounded sterile
      solutions of adenosine are used in cardiac catheterization lab to perform stress
      tests on the heart. These tests are used to determine the fractional flow reserve
      (FFR) and are commonly used in the management and diagnosis of cardiovascular
      conditions. The purpose of this study was to assess the physical and chemical
      stability of 2 mg/mL adenosine in 0.9% Sodium Chloride Injection, USP in
      polyvinyl chloride [PVC]) and polyolefin infusion bags stored at room temperature
      (20 degrees C-25 degrees C) and under refrigeration (2 degrees C-8 degrees C).
      The compounding and analytical methods used in this study were very similar to
      those described in the prior publications from the authors' laboratory. To ensure
      a uniform starting concentration of all stability samples, a batch of 2 mg/mL
      adenosine solution was prepared and then packaged into empty PVC and polyolefin
      infusion bags. These stability samples were prepared in triplicate for each bag
      type and storage temperature (a total of 12 samples). The infusion bag samples
      were assessed for stability immediately after preparation and after 1 day, 3
      days, 7 days, and 14 days. At each time point, the infusion bags were first
      visually inspected against a light background for color change, clarity, and
      particulates. Aliquots were drawn from each sample at each time point for pH
      analysis and high-performance liquid chromatography (HPLC) analysis. Over 14 days
      of storage at room temperature or refrigeration, no considerable change in visual
      appearance or pH was observed in any bags. All samples retained 90% to 110% of
      the initial drug concentration. No significant degradation peaks were observed in
      the HPLC chromatograms.

PMID- 29581598
TI  - Formulary Drug Reviews: Glecaprevir/Pibrentasvir.
AB  - Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well
      documented monographs on drugs that are newly released or are in late phase 3
      trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
      Subscribers also receive monthly 1-page summary monographs on agents that are
      useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
      utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
      month. With a subscription, the monographs are available online to subscribers.
      Monographs can be customized to meet the needs of a facility. Through the
      cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
      this column. For more information about The Formulary Monograph Service, contact
      Wolters Kluwer customer service at 866-397-3433.

PMID- 29581599
TI  - New Medications in the Treatment of Acute Decompensated Heart Failure.
AB  - Acute decompensated heart failure is a sudden worsening of heart failure
      symptoms, typically resulting in peripheral edema and dyspnea as a result of
      pulmonary congestion. Acute decompensated heart failure is responsible for over 1
      million hospitalizations every year. Current pharmacologic therapy is limited in
      its options. Despite an improved survival rate, statistic still suggests that
      about 50% of patients die within 5 years of diagnosis. New pharmacologic agents
      aim to improve efficacy by targeting previously unexplored physiological
      pathways.

PMID- 29581600
TI  - The Prescription Drug User Fee Act: Cause for Concern?
AB  - The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in
      1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue
      in the form of various fees paid by drug and biologic manufacturers. The FDA
      utilizes this revenue to streamline the review and approval process for
      medications. Since the enactment of PDUFA, the median approval time for priority
      new drug applications and biologics license applications has reduced
      significantly. The FDA views PDUFA as a successful program that provides a
      consistent revenue stream to the agency, improves access to medications for
      patients, and allows industry to have a more predictable product review timeline.
      However, critics of PDUFA cite concerns including the potential for a lack of FDA
      independence and medication safety issues involving drugs approved after the
      existence of PDUFA.

PMID- 29581601
TI  - ISMP Medication Error Report Analysis.

PMID- 29581602
TI  - ISMP Adverse Drug Reactions: Minocycline-Induced Drug Fever Without Skin Rash
      Lupus Erythematosus-Like Eruption Induced by Hydroxyurea Cardiotoxicity and Fever
      Induced by Clozapine Denosumab-Induced Hepatotoxicity Severe Cardiotoxicity
      Induced by Bevacizumab.

PMID- 29581603
TI  - Development and Implementation of a Combined Master of Science and PGY1/PGY2
      Health-System Pharmacy Administration Residency Program at a Large Community
      Teaching Hospital.
AB  - Purpose: The purpose of this article is to share experiences after the
      development of a health-system pharmacy administration residency with a MS degree
      and express the need for additional programs in nonacademic medical center health
      system settings. Summary: Experiences with the development and implementation of
      a health-system pharmacy administration residency at a large community teaching
      hospital are described. Resident candidates benefit from collaborations with
      other health-systems through master's degree programs and visibility to leaders
      at your health-system. Programs benefit from building a pipeline of future
      pharmacy administrators and by leveraging the skills of residents to contribute
      to projects and department-wide initiatives. Tools to assist in the
      implementation of a new pharmacy administration program are also described and
      include rotation and preceptor development, marketing and recruiting, financial
      evaluation, and steps to prepare for accreditation. Conclusion: Health-system
      pharmacy administration residents provide the opportunity to build a pipeline of
      high-quality leaders, provide high-level project involvement, and produce a
      positive return on investment (ROI) for health-systems. These programs should be
      explored in academic and nonacademic-based health-systems.

PMID- 29581604
TI  - Breadth of Statistical Training Among Pharmacy Residency Programs Across the
      United States.
AB  - Background: Pharmacy residents' knowledge of biostatistics is a self-identified
      deficit. Objective: To describe statistical training practices across
      postgraduate year 1 (PGY1) pharmacy residency programs and correlate training
      practices with residency program directors' (RPDs) confidence in their residents'
      statistical abilities. Methods: A 13-item survey was sent to PGY1 RPDs and
      included questions regarding respondents' institution, program characteristics,
      type and amount of statistical training offered and desired, as well as
      performance of statistics, resident project publication rates, and RPDs'
      confidence in residents' statistical abilities. Results: Of the 1054 RPDs invited
      to participate in the survey, 202 (19.7%) surveys were completed. Nearly 25% of
      PGY1 pharmacy residency programs in this sample offered no statistical training
      to their residents. The most common types of training were study design
      considerations/selecting statistical tests (64.9%), descriptive statistics
      (59.9%), and database development/data manipulation (46.6%). The majority (60.9%)
      of RPDs had low confidence in their residents' abilities to perform their own
      statistical analysis. After adjusting for significant covariates, residents
      receiving complex statistical training (odds ratio [OR]: 6.76; 95% confidence
      interval [CI]: 2.7-24.9) and a publication rate >50% (OR: 5.63; 95% CI: 1.61
      19.69) were associated with higher RPD confidence in residents' abilities to
      perform statistical analyses. Conclusion: The sample of programs in this survey
      indicates that statistical training for many residents may be limited, and many
      RPDs are not confident in their residents' abilities to perform statistical
      analysis of research projects. Statistical training and opportunities to enhance
      research skills may be an area for future growth in pharmacy residency training
      programs.

PMID- 29581605
TI  - Antihypertensive Prescription Pattern and Compliance to JNC 7 and JNC 8 at
      Tertiary Care Government Hospital, Hyderabad, India: A Cross-sectional
      Retrospective Study.
AB  - Background: The monitoring of hypertension treatment can provide insight into the
      rational drug use pattern. The objective of this study was to examine the
      antihypertensive medication use among South Indian adults with hypertension in
      compliance with the hypertension treatment guidelines (Seventh Joint National
      Committee [JNC 7] and JNC 8). Methods and Results: A total of 550 hypertensive
      people aged >25 years were included in this retrospective cross-sectional study.
      The order of drugs prescribed in the year 2012 was beta blockers (BB) > calcium
      channel blockers (CCB) > CCB + BB > angiotensin receptor blockers (ARB) >
      angiotensin-converting enzyme inhibitors (ACEI) > thiazide diuretics, whereas in
      the year 2014, the order has changed drastically, namely, ACEI > CCB > ARB > BB >
      thiazide diuretics (P < .001). Most notably, there was a large increase in the
      use of monotherapy (from 56.9% to 82.5%, P < .001). The usage of BB has simply
      moved from the first position to the last position in concordance with JNC 8
      guidelines, whereas use of thiazide diuretics was found to be the least preferred
      drug in the 2012 prescriptions, thus deviating from JNC 7 guidelines. The use of
      generic names (28.3% vs 11.3%) and National List of Essential Medicines (NLEM)
      compliance (79.3% vs 60.9%) were significantly more in the calendar year 2012
      than in the calendar year 2014 (P < .001). Conclusions: Antihypertensive
      medication use has gone through wide variations among south Indian adults with
      hypertension. Combination therapy regimens must be adopted as per the guidelines
      for achievement of blood pressure goals.

PMID- 29581606
TI  - Changes in Pharmacy Residency Training Design Between 2012 and 2017: A
      Perspective of Academic Medical Centers.
AB  - Purpose:The role of health-system pharmacists continues to expand, and this area
      of pharmacy practice increasingly requires augmented baseline training. It is
      unclear how Post Graduate Year 1 (PGY-1) pharmacy residencies may be changing to
      meet these needs.The objectives of our survey were to describe PGY-1 pharmacy
      residency program design among academic medical centers, characterize program
      changes enacted over 5-year period, and describe career paths among PGY-1
      pharmacy residency graduates. Methods: A 32-item questionnaire was developed
      independently, which was reviewed and validated by 4 residency program directors.
      The survey was uploaded to an online survey tool and sent electronically to
      residency program directors of 109 Vizient academic medical centers with PGY-1
      pharmacy residency programs. Residency program directors were identified from a
      list of Vizient-participating hospitals. The survey was re-sent at 2-week
      intervals on 4 occasions to improve response rates. SPSS version 23.0 was used to
      analyze the data. Results: Overall, 49 (45%) of hospitals responded to the
      survey. Survey responses showed statistically significant increases over the 5
      year survey period in the following areas: the number of PGY-1 resident positions
      offered (P = .001), percent of time spent on teaching experiences (P = .001), and
      percentage of PGY-1 residents pursuing PGY-2 or fellowship training (P = .026).
      Conclusion: We found that PGY-1 pharmacy residency programs at Vizient academic
      medical centers have undergone limited changes over the 5-year survey period and
      substantial variation exists between program designs. The most common change to
      program design was an increase in the percentage of time residents spend on
      teaching experiences. There was an increase in residents pursuing PGY-2 or
      fellowship training, which may suggest a shift toward increased specialization in
      clinical pharmacy practice or may reflect changes in the availability of job
      opportunities.

PMID- 29581607
TI  - Incidence of Hypoglycemia in Burn Patients: A Focus for Process Improvement.
AB  - Background: Glycemic control in burn patients is critical for reducing infection
      and mortality. Objective: This study was conducted to assess the incidence and
      outcomes of hypoglycemia during continuous insulin infusions (CII). Methods: This
      institutional review board-approved study was a retrospective, single burn
      center, electronic chart review. Patients admitted between January 1, 2013, and
      October 31, 2014, who received a CII were included. Patients with incomplete data
      or who received <24 hours of CII were excluded. Results: Thirty-eight patients
      met inclusion criteria; 6 were excluded. The average patient was a 52-year-old
      Caucasian male with a 33% total body surface area burn and an acute physiology
      and chronic health evaluation (APACHE) II score of 20.Hypoglycemia was present
      for 87 of 6540 hours of CII therapy (1.1%). Two-thirds experienced a serum
      glucose <70 mg/dL and half <60 mg/dL. The most commonly assessed reasons for the
      hypoglycemic episodes were protocol violations (47%) and glucose variability
      (30%). After multivariable logistic regression, only history of diabetes remained
      a statistically significant risk factor with an odds ratio of 15.4 (95%
      confidence interval: 2.5-95.1). Four different CII protocols were prescribed. All
      protocols had a high glucose variability, as assessed by hours / day within goal
      range (13.1 +/- 2.5, 14.1 +/- 3.1, 14.3 +/- 2.4, 9.8; P = .282). Conclusion: The
      amount of different protocols likely contributed to protocol violations and
      glucose variability. Our data demonstrate the need to create and consolidate
      usage to a single protocol in attempts to improve glycemic control.

PMID- 29581608
TI  - Physical Compatibility of Micafungin With Sodium Bicarbonate Hydration Fluids
      Commonly Used With High-Dose Methotrexate Chemotherapy.
AB  - Purpose: The purpose of this study was to determine the physical compatibility of
      micafungin with commonly used concentrations of sodium bicarbonate hydration
      fluids administered via a Y-site connected to a central venous catheter (Y
      site/CVC). Methods: Micafungin sodium (evaluated concentration of 1.5 mg/mL) was
      combined in a 3:1 (vehicle:drug) ratio with the following commonly used hydration
      vehicles: 40 mEq/L sodium bicarbonate in 5% dextrose in water with 1/4 normal
      saline (40SB-D5W-1/4NS), 75 mEq/L sodium bicarbonate in D5W (75SB-D5W), and 154
      mEq/L sodium bicarbonate in D5W (154SB-D5W). A 3:1 ratio was used based on the
      flow rates (typically 125 mL/m2/h for bicarbonate-containing vehicles and 50 mL/h
      for micafungin) of the corresponding solutions in a clinical setting. Visual
      observations recorded to determine physical compatibility included visual
      inspection against different backgrounds (unaided, black, and white). Other
      physical observations were as follows: odor, evolution of gas, pH, and turbidity
      immediately recorded after mixing and at specified time points up to 2 hours.
      Evaluations at each time point were compared against baseline observation values
      at Time 0. Results: All combinations tested were found to be compatible up to 2
      hours. Time points beyond 2 hours cannot be safely verified as compatible.
      Conclusion: Micafungin may be administered safely using a Y-site/CVC delivery
      system with all the vehicles tested in this study.

PMID- 29581609
TI  - <Editors' Choice> Surgical outcomes of decompressive laminoplasty with spinous
      process osteotomy to treat lumbar spinal stenosis.
AB  - Decompressive laminoplasty with spinous process osteotomy (LSPO) was developed as
      a less invasive procedure for lumbar decompression by Weiner et al. There are few
      reports extensively highlighting the surgical outcomes of LSPO. The purpose of
      this study was to evaluate the surgical outcomes of LSPO for lumbar spinal
      stenosis (LSS). In total, 23 patients with LSS were studied. All patients were
      followed up for more than 2 years. The Japanese Orthopedic Association (JOA)
      scores, the recovery rate (RR) of JOA scores, Visual analog scale (VAS) scores,
      responses to the JOA Back Pain Evaluation Questionnaire (JOABPEQ), sagittal
      alignment and segmental motion following LSPO were assessed preoperatively and 2
      years postoperatively. Postoperative paravertebral muscle atrophy and bone union
      rates between the spinous process and the residual laminae were assessed.
      Preoperative and 2-year postoperative JOA scores were 13.0 points and 24.7
      points, respectively (p<0.001). With respect to JOABPEQ, significant improvements
      were observed in pain-related disorders (p<0.05), walking ability (p<0.01),
      social life function (p<0.05), and mental health (p<0.05) dimensions. There were
      no significant differences between preoperative and 2-year postoperative sagittal
      alignment and range of motion. The degree of the paravertebral muscle atrophy at
      2 years postoperatively was 23.0 % at spread side and 9.6 % at nonspread side
      (p<0.01). The fusion rate of the spinous process with the arcus vertebrae was
      87%. This result reveals that LSPO could acquire the reconstruction of posterior
      supporting structures. We demonstrated that LSPO could be a one of the surgical
      options for LSS.

PMID- 29581610
TI  - Estimated costs for treatment and prophylaxis of newborn vitamin K deficiency
      bleeding in Tashkent, Uzbekistan.
AB  - Vitamin K deficiency bleeding (VKDB) is a preventable cause of infant mortality
      and long-term morbidity through the world. This study aimed to demonstrate the
      costs of VKDB treatment estimated from the hospital records in Tashkent,
      Uzbekistan, as well as the prophylaxis costs for mass vitamin K medication.
      Subjects were 50 patients with no operation and 50 patients who had received a
      brain operation, consecutively enrolled from 180 cases diagnosed at Republican
      Research Center of Emergency Medicine in 2014. In that year, an additional 22
      VKDB patients were found in Tashkent; the incidence of VKDB was 478/100,000 among
      42,225 newborns. The prophylaxis costs for all newborns in Tashkent were
      estimated under a plausible condition. The average age at admission was 43.2 days
      among 100 patients (67 boys and 33 girls) with birth weight from 2,600 g to 3,800
      g (3,105 g on average). The great majority of patients (92.0%) were breastfed;
      89.5% in boys and 97.0% in girls. Average treatment cost per VKDB patient was 365
      USD for the operated and 285 USD for the non-operated. Total expenses of the 202
      patients were estimated to be 64,603 USD. A single prophylaxis was estimated to
      cost 1.24 USD, totaling 52,359 USD for the prophylaxis of 42,225 newborns. Since
      the reduction of VKDB incidence through prophylaxis is considered to be higher
      than 78.5% (52,359/64,603), provision of prophylaxis services would reduce the
      total costs of VKDB treatment in Uzbekistan, where prophylaxis is not provided.

PMID- 29581611
TI  - Obesity does not affect peri- and postoperative outcomes of transabdominal
      laparoscopic adrenalectomy.
AB  - Laparoscopic adrenalectomy is the gold standard procedure for most adrenal
      tumors. Obesity is considered as a risk factor for surgical complications. This
      study aimed to evaluate whether obesity affects peri- and postoperative outcomes
      of transabdominal laparoscopic adrenalectomy using body mass index (BMI). This
      retrospective study included 98 patients who underwent transabdominal
      laparoscopic adrenalectomy between January 2011 and December 2016. We divided the
      patients into 2 groups: non-obese group (BMI < 25 kg/m2) and obese group (BMI >=
      25 kg/m2). We assessed perioperative outcomes and postoperative complications
      between the groups. A total of 98 patients were analyzed (70 without obesity and
      28 with obesity). There were no significant differences between the non-obese and
      obese groups regarding operative time (111 vs 107 min; p = 0.795), blood loss
      (3.5 vs 3.5 ml; p = 0.740), rate of placement of additional trocars (14.3% vs
      17.9%; p = 0.657), rate of open conversion (2.6% vs 3.6%; p = 0.853), and
      postoperative length of hospital stay (6 vs 5 days; p = 0.237). Furthermore,
      obesity was not a significant risk factor for postoperative complications
      (postoperative bleeding, wound infection, and pneumonia). There are no
      significant differences in peri- and postoperative outcomes of transabdominal
      laparoscopic adrenalectomy in patients with obesity compared with those without
      obesity. Transabdominal laparoscopic adrenalectomy is feasible and safe for
      patients with obesity.

PMID- 29581612
TI  - Association between the perspective of adult inpatients with digestive cancer
      regarding the nursing service and their quality of recovery on postoperative day
      3.
AB  - Although qualitative research that focuses on inpatients' experience immediately
      after surgery has continued to elucidate the efficacy of the nursing service for
      postoperative recovery, there has been little quantitative research. Our aim was
      to quantitatively clarify the association between inpatients' perception of the
      nursing service and the quality of postoperative recovery. Seventy-one digestive
      cancer patients who underwent surgery were recruited. Participants completed two
      self-administered questionnaires, including the Japanese version of the 40-item
      postoperative Quality of Recovery scale (QoR-40J) and the Nursing Service Quality
      Scale for Japan (NURSERV-J) which has 22 items and five dimensions (tangibles,
      reliability, responsiveness, assurance, and empathy) on postoperative day 3.
      There were significant positive associations between the global scores of the
      NURSERV-J and the QoR-40J. The global score of the QoR-40J was compared between
      patients who gave full marks for each dimension of the NURSERV-J (the entirely
      satisfied group) and those who did not (the not entirely satisfied group). The
      entirely satisfied groups regarding tangibles, reliability and responsiveness had
      a significantly higher global score for the QoR-40J than the respective not
      entirely satisfied groups. Adjusted for age, gender, operative procedure, and
      duration of surgery, the entirely satisfied groups regarding tangibles and
      responsiveness had a significant higher global score for the QoR-40J than the
      respective not entirely satisfied groups. Patients who perceived that they had
      received a nursing service of high quality were likely to attain a high quality
      of postoperative recovery. Nursing services related to tangibles, reliability,
      and responsiveness especially contributed to postoperative recovery.

PMID- 29581613
TI  - Intra-articular platelet-rich plasma (PRP) injections for treating knee pain
      associated with osteoarthritis of the knee in the Japanese population: a phase I
      and IIa clinical trial.
AB  - Intra-articular platelet-rich plasma (PRP) injection has been found to be
      effective for treating osteoarthritis in patients from Western countries;
      however, the safety and efficacy of PRP have not been sufficiently investigated
      in Japanese patients. The present study aimed to evaluate the safety and
      feasibility of intra-articular PRP injection in Japanese patients with knee
      osteoarthritis. PRP without white blood cells was prepared using a single-spin
      centrifuge (PRGF-Endoret; BTI Biotechnology Institute, Vitoria, Spain). A 6-mL
      PRP volume was injected in the knee joint three times at 1 week intervals. All
      patients were prospectively evaluated before intervention and at 1, 3, and 6
      months after the treatment. Adverse events, the Visual Analog Scale (VAS) pain
      score, Japanese Knee Osteoarthritis Measure (JKOM) score and Japanese Orthopedic
      Association score were evaluated. Ten patients (all women; average age, 60.6
      years) were treated. Only minor adverse events after injection were noted, and
      symptoms resolved within 48 hours after the injection. The average VAS pain
      scores were 71.6 mm and 18.4 mm at baseline and the 6-month follow-up,
      respectively (P < 0.05). At the 6-month follow-up, 80% of patients had a decrease
      in the VAS pain score of 50% or more. The average JKOM scores were 35.2 and 14.3
      at baseline and at the 1-month follow-up, respectively (P < 0.05). Intra
      articular PRP injection likely represents a safe treatment option for Japanese
      patients with mild-to-moderate knee osteoarthritis, and has the potential to
      relieve pain for up to 6 months, but further study is needed to verify the
      efficacy.

PMID- 29581614
TI  - Effect of spinal tap test on the performance of sit-to-stand, walking, and
      turning in patients with idiopathic normal pressure hydrocephalus.
AB  - The aim of the study was to investigate the effect of the spinal tap test on sit
      to-stand (STS), walking, and turning and to determine the relationship among the
      outcome measures of STS, walking, and turning in patients with iNPH. Twenty-seven
      patients with clinical symptoms of iNPH were objectively examined for STS,
      walking, and turning by the Force Distribution Measurement (FDM) platform
      connected with a video camera. Assessments were performed at before and 24 hours
      after spinal tap. Motor abilities were assessed by the STS time, time of walking
      over 3 meters, and time and number of steps when turning over 180 degrees.
      Significant improvements were found in the STS time (p = 0.046), walking time (p
      = 0.048), and turning step (p = 0.001). In addition, turning time was improved
      but not statistically significant (p = 0.064). Significant relationships were
      found among all outcome measures (p < 0.001). The relationship among these
      outcome measures indicated that the individuals had similar ability levels to
      perform different activities. This may serve as a new choice of outcome measures
      to evaluate the effect of intervention in different severity levels of patients
      with iNPH.

PMID- 29581615
TI  - Factors related to sense of coherence in adult patients with Type 2 diabetes.
AB  - The influence of a diabetic person's sense of burden and blood sugar control
      through sense of coherence (SOC) on self-management has yet to be sufficiently
      clarified. The purpose of this study was to examine the utility of salutogenesis,
      which has sense of coherence at its core, for the self-management of patients
      with type 2 diabetes. A total of 258 questionnaires were distributed to patients
      who were seen at one of three hospitals in an urban area in Japan, after
      obtaining consent from the patient. They were between 20 and 75 years old and
      regularly received care. Of the 185 responses, 177 were valid. The responses were
      analyzed by referring to the framework of salutogenesis, and the relationship
      between patient characteristics, SOC, the Problem Areas In Diabetes survey
      (PAID), and glycosylated hemoglobin (HbA1c) were studied with structural equation
      modeling (SEM). SOC had a main effect on PAID scores and an indirect effect on
      HbA1c. Moreover, age influenced SOC positively. The SOC of patients with type 2
      diabetes in the present study was comparatively high. These observations suggest
      a direct effect of SOC on reducing the sense of burden from having diabetes and
      an indirect effect on decreasing HbA1c. This research suggested the possibility
      that diabetes can be controlled by improving SOC.

PMID- 29581616
TI  - Medical clerks in a national university hospital: improving the quality of
      medical care with a focus on spinal surgery.
AB  - In our institution, which is a national university hospital, medical clerks were
      introduced in 2009 to improve the doctor's working environment. Seventeen clerks
      were assigned to 9 separate departments and the work content differed greatly
      among departments, but sufficient professional work was not done efficiently. The
      purpose of this study is to investigate the effects of the work of medical clerks
      on improvement of medical quality in recent years. In 2011, we established a
      central clerk desk on our outpatient floor to improve efficiency and centralize
      the clerk work. Since 2013, periodic education of clerks on spine disease has
      been provided by spine doctors, and this has facilitated sharing of information
      on spinal surgery from diagnosis to surgical treatment. This has allowed medical
      clerks to ask patients questions, leading to more efficient medical treatment and
      a potential reduction of doctors' work. In 2016, a revision of the insurance
      system by the Ministry of Health, Labour and Welfare of Japan increased the
      amount of medical work that clerks can perform, and it became possible to
      increase the number of medical clerks. Currently, we have 30 medical clerks, and
      this has allowed establishment of new clerk desks in other departments to handle
      patients. A training curriculum will be developed to reduce the burden on doctors
      further and to improve the quality of medical treatment.

PMID- 29581617
TI  - National survey of international electives for global health in undergraduate
      medical education in Japan, 2011-2014.
AB  - Interest in global health in medical education is increasing in Western
      countries, whereas data from non-Western countries is scarce. Here, we conducted
      a nationwide study of international clinical electives at Japanese medical
      schools from 2011 to 2013. We constructed a 28-item cross-sectional survey in
      Japanese to investigate the rate and characteristics of both Japanese students
      going abroad and international students coming on exchange to Japan. The surveys
      were sent to the administrative offices of all 80 Japanese medical schools in
      each of the three years, through the Japan Medical Education Foundation. All 80
      medical schools responded to the questionnaire (response rate, 100%). An average
      of 70 of the 80 medical universities provided exchange programs across the three
      years to allow students to travel abroad as part of the school curriculum and
      obtain academic credit. The schools provided support in the form of in- and
      outside-class preparatory programs, tuition fee exemptions and housing. The most
      popular destinations for Japanese students going abroad were Europe and North
      America, which may reflect the desire of Japanese students to acquire medical
      knowledge or experience through exposure to the English language. In contrast,
      the most common countries of origin of international exchange students coming to
      Japan were Asian countries such as South Korea, Thailand and Taiwan, with
      pediatrics being the most popular elective. Foreign exchange programs are
      becoming increasingly incorporated into the Japanese medical education curriculum
      and can help to strengthen international partnerships and collaborations.

PMID- 29581618
TI  - <Editors' Choice> Maxillary sinus carcinoma outcomes over 60 years: experience at
      a single institution.
AB  - Advances in the diagnosis and treatment of patients with maxillary sinus
      carcinoma have improved patient prognosis. This study investigated changes in
      demographic and clinical characteristics, treatment methods, and outcomes of
      patients with maxillary sinus carcinomas during three different 10-year periods
      spanning 60 years at our university hospital. Of the 233 patients with maxillary
      sinus carcinomas managed at Nagoya University Hospital, 135 were treated between
      1951 and 1960 (first period), 35 between 1981 and 1990 (second period), and 63
      between 2003 and 2012 (third period). Patient age, sex, TN classifications,
      treatment methods, and survival rates were compared among patients treated during
      these time periods. Of the 135, 35, and 63 patients with maxillary sinus
      carcinomas treated during these time periods, 86 (63.7%), 21 (51.4%), and 48
      (76.2%), respectively, were men; 14 (10.4%), six (17.1%), and 14 (22.2%),
      respectively, were aged >=70 years; and 135 (100%), 28 (80.0%), and 43 (68.3%),
      respectively, were treated surgically. The 5-year overall survival rates in
      patients treated during the first, second, and third periods were 29.7%, 44.3%,
      and 57.5%, respectively. These findings indicated that advances in the diagnosis
      and treatment of patients with maxillary sinus carcinoma, including computed
      tomography and craniofacial resection, have contributed to improvements in
      patient survival rates.

PMID- 29581619
TI  - Identifying the social capital influencing diabetes control in Japan.
AB  - The number of patients with diabetes is increasing in Japan. Recently, Social
      capital (SC) has received increasing attention as a factor influencing health
      conditions. In the US, the relation between SC and diabetes control has been
      reported, but little attention has been paid to this connection in Japan. Three
      SC questionnaires, entitled "trust in people in a community," "social support,"
      and "social relationships," were constructed. The subjects were adult patients
      with type 2 diabetes. Information on diabetic conditions, such as HbA1c, self
      attainment of diet (SAD) and exercise (SAE), and complications were collected.
      The reliability coefficients for the SC questionnaire and factor analysis of SC
      were conducted. Multiple and logistic regressions were used to identify the
      influence of SC on diabetes control. Sixty-five patients participated in this
      study. The questionnaires "social support" and "social relationships" were
      adopted to measure Cronbach alpha coefficient. Factor analysis extracted the
      factors "hope to be helped (HH)," "participation in favorite events (PFE),"
      "sense of belonging (SB)," and "social movement (SM)." HbA1c was positively
      correlated with HH (P < 0.05). SAD and SAE were negatively correlated with HH (P
      < 0.05). SAE was positively correlated with PFE (P < 0.05). PFE reduced
      complication risks (P < 0.05). HH includes amae, which negatively affected self
      efficacy that correlates with diabetes control. Therefore, higher HH might cause
      higher levels of HbA1c. PFE reduces distress and contributes to glucose control.
      Reduced distress through PFE might prevent complications. HH and PFE were
      identified as SC that influences diabetes control.

PMID- 29581620
TI  - Genome-wide association study for pollinosis identified two novel loci in
      interleukin (IL)-1B in a Japanese population.
AB  - The number of pollinosis patients in Japan has significantly increased over the
      past 20 years. The majority of genome-wide association studies (GWAS) on
      pollinosis have been conducted in subjects of European descent, with few studies
      in Japanese populations. The aim of our GWAS was to identify genetic loci
      associated with self-reported pollinosis in a Japanese population and to
      understand its molecular background using a combination of single nucleotide
      polymorphisms (SNPs) and gene- and pathway-based analyses. A total of 731 and 560
      individuals who were recruited as participants of the Japan Multi-Institutional
      Collaborative Cohort Study participated in the discovery and replication phases,
      respectively. The phenotype of pollinosis was based on the information from a
      self-administered questionnaire. In the single-SNP analysis, four SNPs
      (rs11975199, rs11979076, rs11979422, and rs12669708) reached suggestive
      significance level (P < 1 * 10-4) and had effects in the same direction in both
      phases of the study. The pathway-based analysis identified two suggestive
      pathways (nucleotide-binding oligomerization domain -like receptor and tumor
      necrosis factor signaling pathways). Both rs1143633 and rs3917368 in the
      interleukin-1B gene showed associations in the retrace (from pathway to gene and
      SNP) analysis. We performed single-SNP, gene, and pathway analysis and shed light
      on the molecular mechanisms underlying pollinosis in a Japanese population.

PMID- 29581621
TI  - Clinical significance of gastrointestinal patency evaluation by using patency
      capsule in Crohn's disease.
AB  - Capsule endoscopy (CE) enables noninvasive visualization of the small bowel in
      Crohn's disease (CD), but should not be conducted in patients with bowel
      obstruction. Patency capsule (PC) can be ingested before conducting the CE
      examination to ensure patency of the gastrointestinal (GI) tract. This study
      aimed to evaluate the clinical significance of GI patency which the PC
      demonstrated. A retrospective review of the medical records was conducted with 99
      consecutive patients with CD who underwent PC and CE at Nagoya University
      Hospital from January 2010 to May 2015. By using the Cox proportional hazards
      model, the association between the GI patency evaluated using the PC and the
      outcome in terms of the rate of patients who needed admission or surgery during
      the 2-year follow-up was examined. Of all 99 patients who ingested the PC, 84
      (84.8%) were diagnosed as not having bowel obstruction, and therefore were
      eligible for CE (P group). Of the 15 patients in whom bowel obstruction was
      suspected (NP group), 12 patients underwent either the balloon-assisted endoscopy
      (n=10) or enteroclysis (n=2), and 11 were confirmed to have small bowel
      stricture. Non-admission rates of the P and NP groups during the 2-year
      observation period were 74/84 (88.0%) and 8/15 (53.3%), respectively (P<0.001).
      Non-operation rates of the P and NP groups during the 2-year observation period
      were 80/84 (95.2%) and 9/15 (60.0%), respectively (P<0.001). In conclusion, GI
      patency as diagnosed using the PC was associated with a significantly lower
      incidence of admission or surgical intervention.

PMID- 29581622
TI  - Bevacizumab-induced tracheoesophageal fistula in a patient suffering from lung
      cancer with bulky subcarinal lymph node: a case report.
AB  - A 66-year-old male with advanced non-small-cell lung cancer (NSCLC) who was
      previously treated with carboplatin, pemetrexed, and bevacizumab consequently
      suffered from severe coughing during deglutition. Chest computed tomography (CT)
      revealed a tracheoesophageal fistula (TEF) between the left main bronchus and
      esophagus through a subcarinal metastatic lymph node. Given the extreme swelling
      of the lymph node due to metastatic cancer, it was determined that the walls of
      the bronchus and esophagus had been injured simultaneously. Delayed and
      dysfunctional wound healing due to bevacizumab resulted in necrosis of the
      contact region leading to fistula formation. This case suggests that using
      bevacizumab for NSCLC in patients with bulky subcarinal lymphadenopathy may
      increase the risk for TEF.

PMID- 29581624
TI  - Time for a new resistance against antibiotics.

PMID- 29581623
TI  - A case of local recurrence of T1 rectal cancer 10 years after transanal excision.
AB  - We report a case of a patient with T1 rectal cancer, which recurred locally after
      10 years from the primary operation. A 78-year-old woman was diagnosed with
      rectal cancer. Transanal excision (TAE) was performed in December 2006. The
      pathological findings revealed stage I rectal cancer [tub2>muc, pSM (2,510 um),
      ly0, v0, pHM0, pVM0]. Because she did not opt for additional treatment, she
      received follow-up examination. After approximately 10 years from the primary
      operation, she presented to her physician, complaining of melena, and she was
      referred to our hospital again in November 2016. She was diagnosed with recurrent
      rectal cancer. Laparoscopic abdominoperineal resection was performed in December
      2016. Pathological findings revealed stage IIIB rectal cancer (tub2>muc, pA,
      pN1). The reported postoperative local recurrence rate for T1 rectal cancer after
      TAE is high, but local recurrence after years from the primary operation is rare.
      In high-risk cases, local recurrence may be observed even after 10 years from the
      primary operation. Long-term and close postoperative follow-up is important to
      detect local recurrence early.

PMID- 29581626
TI  - Understanding Acid-Base Disorders.

PMID- 29581627
TI  - Vaginal Hysterectomy using the ERBE BiClamp(r) Bipolar Vessel Sealing System: A
      Case Series.
AB  - The ERBE BiClamp(r) BVSS appears to be a safe and effective method of vaginal
      hysterectomy in this small single surgeon, single institution study;
      demonstrating efficient operative times, minimal blood loss and intraoperative
      morbidity with acceptable surgical outcomes. Its use contributes to the
      advancement of minimally invasive gynaecology and should be encouraged.

PMID- 29581628
TI  - The Effect of Interval From Completion of Short-Course Radiotherapy to Surgery on
      the Post-Operative Morbidity and Mortality of Patients with Rectal Cancer.
AB  - Aim: Surgery is the mainstay of treatment for invasive rectal cancer. Advances in
      surgical technique and radiotherapy over the past few decades have resulted in
      improved local control and survival.1-3 Some concern remains regarding the
      morbidity associated with performing surgery within a short window following
      radiotherapy. The current study assessed whether the interval between short
      course radiotherapy and surgery influences all cause post-operative morbidity and
      mortality. Methods: All patients who had undergone short-course radiotherapy for
      rectal cancer within the Belfast Health and Social Care Trust from 2005 to 2014
      held on a prospective database were included (n=102). A retrospective review of
      patients' clinical records was performed and a comparison made of patients who
      had undergone surgery less than 4 days with those 4 or more days following
      completion of radiotherapy. Baseline patient and tumour characteristics, post
      operative complications and readmission rates were compared. Statistical analysis
      was performed using SPSS (r), Version 22 (SPSS, Inc, Chicago, Illinois, USA).
      Results: There was no significant difference in mortality or overall post
      operative complications between groups, however, less serious complications were
      reduced in patients undergoing surgery less than 4 days following radiotherapy.
      Perineal wound complications were significantly more common in patients who had
      undergone surgery 4 or more days following radiotherapy. Conclusion: Our results
      support the existing data that post-operative complications may be more common
      with increasing interval to surgery from completion of radiotherapy. Perineal
      wound morbidity appears significantly more common in patients who undergo surgery
      4 or more days following short-course radiotherapy. A larger study to look
      particularly at perineal wound morbidity and interval from completion of
      radiotherapy is warranted.

PMID- 29581629
TI  - Long Term Follow Up of Male Breast Cancer.
AB  - Introduction: Male breast cancer accounts for less than 1% of breast cancers with
      published overall and disease free survival being lower than in females. Aims: To
      determine treatment and long term outcomes for male breast cancer patients in our
      unit. Methods: A database has been maintained for all breast cancer patients
      diagnosed in our unit since 1993. Patients were identified using the database and
      information was collated on patient demographics, tumour pathology, treatment and
      outcomes using the database and retrospective chart review. Patients were
      followed to cause of death. Results: From 1994-2009 twenty-four cancers were
      diagnosed in twenty-two patients. Mean age at diagnosis was 69. Male breast
      cancer patients were treated using similar principles to female breast cancer.
      Twenty patients underwent mastectomy, two patients underwent wide local excision.
      No patients developed local recurrence. One patient died from their breast cancer
      with systemic metastases. 10-year overall survival was 22%, 10 year disease
      specific survival was 80%. Other causes of death included medical co-morbidity
      and secondary cancers. Discussion: Disease free survival in our unit is
      comparable to other published studies. High age at diagnosis and co-morbidity are
      the most important factors in determining overall outcome. Treatment pathways for
      male breast cancer should follow guidelines for female disease in order to
      optimise outcomes. Future research at national or international level is
      necessary to ensure the most effective treatments are implemented for male breast
      cancer patients.

PMID- 29581630
TI  - Minimally Invasive management of delayed recognition iatrogenic ureteric injury.
AB  - Introduction: Iatrogenic ureteric injuries are a rare but serious complication of
      abdomino-pelvic surgery which can be associated with significant morbidity. 65
      80% of ureteric trauma is only identified in the postoperative period. Current
      guidelines recommend stent insertion or urinary diversion via percutaneous
      nephrostomy. Good quality evidence on success and outcomes remains scant and the
      optimum treatment pathway unknown. Methods: A retrospective review of all delayed
      presentation ureteric injuries treated in our unit between 2005 and 2013 was
      performed. Clinical, treatment and outcome data were collected in a custom
      proforma. Results: 19 patients with 21 injured ureters met inclusion criteria.
      16/19 (84.2%) injuries were sustained during gynaecological procedures with 10
      (52.6%) of these during total abdominal hysterectomy. Suspected mechanisms from
      diagnostic studies was defined as partial transection in 9/21 (42.9%), complete
      transection in 3/21 (14.3%) and perforation in 1/21 (4.8%).Median time from
      injury to presentation was 16 days (IQR 7-25). 11/21 (52.4%) had successful
      stenting with a median time to stent placement of 25 days (IQR 18.5-42). Those
      with failed stenting had a median time to attempted stenting of 65 days (IQR 10
      91.3). Those with successful stenting 3/11 (27.3%) had resolution requiring no
      further intervention. 6/11 (54.5%) required open reconstruction, with the
      remaining two patients unfit for reconstruction and managed with long term
      stents. With successful stenting median time to definitive surgery was 413 days
      (IQR 156-476). Conclusion: Success rates for stenting are similar to those
      reported in the literature (55% vs. 44-59%), but resolution rates are
      significantly lower (15% vs. 44-80%). Data for an endourological approach as a
      possible long-term solution is limited by heterogeneity, and a further well
      conducted multicentre prospective study is required.

PMID- 29581632
TI  - Dr Elizabeth Gould Bell (1862 - 1934) - The First Woman to Graduate In Medicine
      And Practice In Ulster.

PMID- 29581631
TI  - Dystrophin Exon 29 Nonsense Mutations Cause a Variably Mild Phenotype.
AB  - Background: Nonsense mutations in the dystrophin gene usually result in a severe
      Duchenne muscular dystrophy phenotype. Findings: We describe a 7-year-old boy
      with a rare pathogenic mutation in exon 29 c.3940C>T p.(Arg1314Ter) resulting in
      exon skipping, in turn rescuing the phenotype from a severe Duchenne type to a
      milder Becker muscular dystrophy type. No adults have been described with this
      mutation to date. Conclusions: Exon skipping of exon 29 results in a higher level
      of functional dystrophin. Some cases of muscular dystrophy may still require
      muscle biopsy to determine optimal management and pharmaceutical treatment
      options.

PMID- 29581633
TI  - Dr Robert Stephenson's Address to the Belfast Medical Society on 2nd December
      1850.

PMID- 29581634
TI  - Adaptive Learning in Medical Education: The Final Piece of Technology Enhanced
      Learning?
AB  - Technology enhanced learning (TEL) is now common practice in the field of medical
      education. One of the primary examples of its use is that of high fidelity
      simulation and computerised mannequins. Further examples include online learning
      modules, electronic portfolios, virtual patient interactions, massive open online
      courses and the flipped classroom movement. The rise of TEL has occurred
      primarily due to the ease of internet access enabling the retrieval and sharing
      of information in an instant. Furthermore, the compact nature of internet ready
      devices such as smartphones and laptops has meant that access to information can
      occur anytime and anywhere. From an educational perspective however, the current
      utilisation of TEL has been hindered by its lack of understanding of learners'
      needs. This is concerning, particularly as evidence highlights that during
      medical training, each individual learner has their own learning requirements and
      often achieves competency at different rates. In view of this, there has been
      interest in ensuring TEL is more learner aware and that the learning process
      should be more personalised. Adaptive learning can aim to achieve this by
      ensuring content is delivered according to the needs of the learner. This
      commentary highlights the move towards adaptive learning and the benefits of such
      an intervention.

PMID- 29581635
TI  - PARAMILITARY SHOOTINGS AND ASSAULTS.

PMID- 29581636
TI  - AUTHOR'S RESPONSE: PARAMILITARY SHOOTINGS AND ASSAULTS.

PMID- 29581637
TI  - INAPPROPRIATE ED ATTENDANCES IN NORTHERN IRELAND: COMMENT FROM RCGP NORTHERN
      IRELAND.

PMID- 29581638
TI  - AUTHORS' RESPONSE: INAPPROPRIATE ED ATTENDANCES IN NORTHERN IRELAND: COMMENT FROM
      RCGP NORTHERN IRELAND.

PMID- 29581639
TI  - COMPLETE TRANSECTION OF THE RADIAL NERVE ASSOCIATED WITH A CLOSED HUMERAL SHAFT
      FRACTURE.

PMID- 29581640
TI  - ATYPICAL PRESENTATION OF SOFT TISSUE SARCOMA.

PMID- 29581641
TI  - NO BABY BOOM OR SEX RATIO CHANGES FOLLOWING FIFTY SHADES OF GREY IN ENGLAND AND
      WALES.

PMID- 29581642
TI  - IS IT TIME TO REVISIT THE RED FLAG REFERRAL SYSTEM?

PMID- 29581643
TI  - Curiositas (Cardiology).

PMID- 29581644
TI  - AN UPDATE IN AORTIC VALVE INTERVENTION AND EARLY DISCHARGE.

PMID- 29581645
TI  - SENTINEL BIOPSY IN VULVAL CANCER - ESTABLISHING A REGIONAL SERVICE IN NORTHERN
      IRELAND.

PMID- 29581646
TI  - IMMUNOTHERAPY FOR LUNG CANCER - A GAME CHANGER!

PMID- 29581647
TI  - So you want to be an Academic Foundation Programme Doctor?

PMID- 29581648
TI  - Chernoff Index for Cox Test of Separate Parametric Families.
AB  - The asymptotic efficiency of a generalized likelihood ratio test proposed by Cox
      is studied under the large deviations framework for error probabilities developed
      by Chernoff. In particular, two separate parametric families of hypotheses are
      considered (Cox, 1961, 1962). The significance level is set such that the maximal
      type I and type II error probabilities for the generalized likelihood ratio test
      decay exponentially fast with the same rate. We derive the analytic form of such
      a rate that is also known as the Chernoff index (Chernoff, 1952), a relative
      efficiency measure when there is no preference between the null and the
      alternative hypotheses. We further extend the analysis to approximate error
      probabilities when the two families are not completely separated. Discussions are
      provided concerning the implications of the present result on model selection.

PMID- 29581649
TI  - Small Changes Yield Large Results at NIST's Net-Zero Energy Residential Test
      Facility.
AB  - The Net-Zero Energy Residential Test Facility (NZERTF) was designed to be
      approximately 60 % more energy efficient than homes meeting the 2012
      International Energy Conservation Code (IECC) requirements. The thermal envelope
      minimizes heat loss/gain through the use of advanced framing and enhanced
      insulation. A continuous air/moisture barrier resulted in an air exchange rate of
      0.6 air changes per hour at 50 Pa. The home incorporates a vast array of
      extensively monitored renewable and energy efficient technologies including an
      air-to-air heat pump system with a dedicated dehumidification cycle; a ducted
      heat-recovery ventilation system; a whole house dehumidifier; a photovoltaic
      system; and a solar domestic hot water system. During its first year of operation
      the NZERTF produced an energy surplus of 1023 kWh. Based on observations during
      the first year, changes were made to determine if further improvements in energy
      performance could be obtained. The changes consisted of installing a thermostat
      that incorporated control logic to minimize the use of auxiliary heat, using a
      whole house dehumidifier in lieu of the heat pump's dedicated dehumidification
      cycle, and reducing the ventilation rate to a value that met but did not exceed
      code requirements. During the second year of operation the NZERTF produced an
      energy surplus of 2241 kWh. This paper describes the facility, compares the
      performance data for the two years, and quantifies the energy impact of the
      weather conditions and operational changes.

PMID- 29581650
TI  - An Exploration of the Relationship between Improvements in Energy Efficiency and
      Life-Cycle Energy and Carbon Emissions using the BIRDS Low-Energy Residential
      Database.
AB  - To conduct a more complete analysis of low-energy and net-zero energy buildings
      that considers both the operating and embodied energy/emissions, members of the
      building community look to life-cycle assessment (LCA) methods. This paper
      examines differences in the relative impacts of cost-optimal energy efficiency
      measure combinations depicting residential buildings up to and beyond net-zero
      energy consumption on operating and embodied flows using data from the Building
      Industry Reporting and Design for Sustainability (BIRDS) Low-Energy Residential
      Database. Results indicate that net-zero performance leads to a large increase in
      embodied flows (over 40%) that offsets some of the reductions in operational
      flows, but overall life-cycle flows are still reduced by over 60% relative to the
      state energy code. Overall, building designs beyond net-zero performance can
      partially offset embodied flows with negative operational flows by replacing
      traditional electricity generation with solar production, but would require an
      additional 8.34 kW (18.54 kW in total) of due south facing solar PV to reach net
      zero total life-cycle flows. Such a system would meet over 239% of operational
      consumption of the most energy efficient design considered in this study and over
      116% of a state code-compliant building design in its initial year of operation.

PMID- 29581651
TI  - Motion-plane dependency of the range of dart throw motion and the effects of
      tendon action due to finger extrinsic muscles during the motion.
AB  - [Purpose] To clarify the motion-plane dependency of the range of dart throw
      motion and the effects of tendon action due to long finger flexors and extensors
      during the motion. [Subjects and Methods] Forty healthy subjects attended the
      experiment, and the active range of wrist motion in seven motion planes was
      measured with an originally designed apparatus. [Results] The reliability of the
      measurement was acceptable. The range of dart throw motion depended on the motion
      planes, with a maximum at around the motion plane of 45 degrees  from the
      sagittal plane (45 degrees  of pronation). The tendon action of long finger
      muscles was shown in dart throw motion except in 45 degrees  of pronation.
      [Conclusion] Motion-plane dependency of the range of dart throw motion exists in
      healthy subjects. The absence of tendon action due to finger extrinsic muscles in
      dart throw motion at 45 degrees  might be one of the causes of the advantage of
      dart throw motion.

PMID- 29581652
TI  - Effects of extracorporeal shock wave therapy on upper extremity muscle tone in
      chronic stroke patients.
AB  - [Purpose] The purpose of this study was to examine the effects of extracorporeal
      shock wave therapy (ESWT) on upper extremity muscle tone in chronic stroke
      patients. [Subjects and Methods] For this study, 30 stroke patients participated
      in this study and they were divided into ESWT group and sham-ESWT group, each
      group consisted of 15 patients. ESWT and sham-ESWT was performed by the patients
      for two times a week, for eight weeks. MyotonPRO was used to measure muscle tone.
      [Results] According to the results of the comparisons between the groups, after
      intervention, upper extremity muscle tone were significantly higher in the ESWT
      group than in the sham-ESWT group. [Conclusion] This study showed that ESWT is
      effective for improving decrease of muscle tone in chronic stroke patients.

PMID- 29581653
TI  - Effects of mechanical-bed massage on exercise-induced back fatigue in athletes.
AB  - [Purpose] The study aimed to preliminarily investigate the effects of mechanical
      bed massage on exercise-induced back fatigue in athletes. [Subjects and Methods]
      Twelve male college athletes, randomly allocated to experimental or control
      groups, were instructed to perform reverse sit-up for 8 sessions until they
      became fatigued. The experimental group received a 20-min mechanical-bed massage
      session, while the control group rested on a bed for the same period of time.
      Visual Analogue Scale (VAS) on perceived back muscle fatigue, back muscle
      endurance, and Heart Rate Variability (HRV) parameters including stress index
      (SI), HRV index, SDNN, RMSSD, pNN50, LF, HF, and LF/HF were analyzed. [Results]
      Immediately and 24 hours after the intervention, the VAS significantly differed
      between the groups. Experimental group's HF was significantly higher immediately
      after the intervention than control group. Experimental group's LF and LF/HF were
      significantly lower immediately after the intervention than the control group.
      [Conclusion] Mechanical bed massage may help athletes overcome the subjective
      feelings of exercise-induced fatigue, modulate the automatic nervous system
      activity, especially for balancing sympathetic and parasympathetic activities.
      Therefore, mechanical bed massage may facilitate recovery from muscle and central
      fatigue after athlete training or competition.

PMID- 29581654
TI  - The effects of shoulder stabilization exercises and pectoralis minor stretching
      on balance and maximal shoulder muscle strength of healthy young adults with
      round shoulder posture.
AB  - [Purpose] The purpose of this study was to analyze the effects of pectoralis
      minor stretching and shoulder strengthening with an elastic band on balance and
      maximal shoulder muscle strength in young adults with rounded shoulder posture.
      [Subjects and Methods] Nineteen subjects with rounded shoulder posture were
      randomly divided into 2 groups: a shoulder stabilization exercise group and a
      stretching exercise group. The groups performed each exercise for 40 minutes, 3
      times a week, for 4 weeks. Static balance (eyes open and closed), dynamic balance
      (the limits of stability in 4 directions) and shoulder muscle strength in 5
      directions were measure before and after the exercises. [Results] The stretching
      exercise demonstrated a significant difference between the pre- and post-exercise
      in the static balance with eyes closed and extension and horizontal abduction
      strength while the stabilization exercise demonstrated significant difference in
      the left and right directions between the pre- and post-exercise of the dynamic
      balance and flexion strength. The stabilization exercise demonstrated significant
      differences shown in the flexion between the pre- and post-test. [Conclusion] The
      shoulder stabilization and stretching exercises improved the static balance,
      dynamic balance, and muscle strength.

PMID- 29581655
TI  - Effect of squatting velocity on hip muscle latency in women with patellofemoral
      pain syndrome.
AB  - [Purpose] Neuromuscular activity has been evaluated in patellofemoral pain
      syndrome but movement velocity has not been considered. The aim was to determine
      differences in onset latency of hip and knee muscles between individuals with and
      without patellofemoral pain syndrome during a single leg squat, and whether any
      differences are dependent on movement velocity. [Subjects and Methods] Twenty
      four females with patellofemoral pain syndrome and 24 healthy females
      participated. Onset latency of gluteus maximus, anterior and posterior gluteus
      medius, rectus femoris, vastus medialis, vastus lateralis and biceps femoris
      during a single leg squat at high and low velocity were evaluated. [Results]
      There was an interaction between velocity and diagnosis for posterior gluteus
      medius. Healthy subjects showed a later posterior gluteus medius onset latency at
      low velocity than high velocity; and also later than patellofemoral pain syndrome
      subjects at low velocity and high velocity. [Conclusion] Patellofemoral pain
      syndrome subjects presented an altered latency of posterior gluteus medius during
      a single leg squat and did not generate adaptations to velocity variation, while
      healthy subjects presented an earlier onset latency in response to velocity
      increase.

PMID- 29581656
TI  - Limb-dominance and gender differences in the ground reaction force during single
      leg lateral jump-landings.
AB  - [Purpose] The purpose of this study was to examine limb-dominance and gender
      differences in the magnitude of the ground reaction force during single-leg
      lateral jump-landings. We hypothesized that the peak ground reaction force would
      be larger in the non-dominant leg compared to that in the dominant leg and would
      be larger in females compared to that in men. [Subjects and Methods] Fifteen
      females and 15 males performed jump-landings sideways from a height of 20 cm,
      with a lateral distance of 60 cm. Vertical and medial ground reaction forces were
      measured, and the elapsed time from the initial contact to the peak ground
      reaction force was determined. The loading rate was calculated as the peak ground
      reaction force divided by the elapsed time from the initial contact to the peak
      ground reaction force. [Results] The vertical and medial peak ground reaction
      forces during single-leg lateral jump-landings were larger in females compared to
      that in males. In addition, the medial peak ground reaction force was larger for
      the non-dominant leg compared to that for the dominant leg. [Conclusion] The
      results suggest that in rehabilitation and conditioning settings, evaluations and
      instructions regarding attenuation are especially important for females and the
      non-dominant leg.

PMID- 29581658
TI  - Effect of interferential current therapy on forward head posture.
AB  - [Purpose] The purpose of this study was to examine the effects of interferential
      current therapy on the shoulder muscles of subjects with forward head posture.
      [Subjects and Methods] Thirty volunteers (15 forward head posture, 15 control)
      participated in this study. Interferential current therapy treatment was
      conducted for 10 min, three times per week, for 3 weeks on both the upper
      trapezius and levator scapulae. Subjects were measured anterior both acromion
      distance and posterior both acromial distance using a ruler, and the forward head
      posture angle using an electronic application. [Results] Both groups showed
      significant increases in anterior acromial distance, and decreases in posterior
      acromial distance and forward head posture angle. [Conclusion] Subjects were
      concluded that electrical therapy could improve structural alignment; therefore,
      the implementation of interferential current therapy is expected to be effective
      for the treatment of forward head posture.

PMID- 29581657
TI  - Effects of anterior weight-shifting methods on sitting balance in wheelchair
      dependent patients with spinal cord injury.
AB  - [Purpose] This study aimed to compare changes in the center of pressure between
      healthy subjects and patients with spinal cord injury and to provide basic
      information to these patients for improving their sitting balance. [Subjects and
      Methods] A total of 12 healthy subjects without histories of neurological or
      psychiatric disorders and 12 patients with spinal cord injuries were recruited.
      In all subjects, a change in the center of pressure during the performance of the
      modified functional reach test was measured using a Force Sensing Array system
      while the subjects were seated in a wheelchair. In the spinal cord injury group,
      the change in the center of pressure was highest when subjects reached forward
      while holding a gym ball. [Results] In the spinal cord injury group, the change
      in the center of pressure was highest when subjects reached forward while holding
      a gym ball. A significant correlation between forward reaching of the upper limbs
      with shoulders at 90 degrees  flexion and a change in the center of pressure was
      found. [Conclusion] Our findings suggest that the combination of functional
      reaching and the change in the center of pressure assessment is novel enough to
      be attempted to achieve sitting balance control in patients with spinal cord
      injury. The findings can provide clinical interventions that contribute to the
      improvement in the balance ability of wheelchair-dependent individuals.

PMID- 29581659
TI  - Effects of stabilization exercise using flexi-bar on functional disability and
      transverse abdominis thickness in patients with chronic low back pain.
AB  - [Purpose] The purpose of this study is to examine the effects of lumbar
      stabilization exercises using flexi-bar (FB) on pain, functional disability,
      transverse abdominis muscle (TrA) activation capacity and thickness in patients
      with chronic low back pain (CLBP). [Subjects and Methods] Twenty-seven patients
      were randomly assigned to an experimental (14 patients performing stabilization
      exercises with flexi-bar (FB)) or control (13 patients performing stabilization
      exercises) group. The patients in both groups then underwent stabilization
      exercises with or without FB 30 min/day, 3 times a week, for 6 weeks. The main
      outcome measures were perceived disability based on the pain, Oswestry disability
      index (ODI), TrA activation capacity and thickness. [Results] Both groups showed
      improved ODI, VAS, and TrA activation capacity performed for 6 weeks in patients
      with CLBP, but all outcomes, except for TrA thickness, showed greater
      improvements in patients following stabilization exercises with FB than following
      stabilization exercises. [Conclusion] Based on the above results, lumbar
      stabilization exercises with FB could restoring pain, functional disability and
      improving TrA activation capacity in CLBP patients.

PMID- 29581660
TI  - Postural stability for taekwondo athletes with repetitive ankle sprains during a
      single-leg stance.
AB  - [Purpose] The purpose of this study is to investigate postural stability in such
      group of taekwondo athletes by measuring the center-of-pressure variables in both
      the injured limb and uninjured limb during a single-leg stance with eyes closed.
      [Subjects and Methods] The study includes eleven taekwondo athletes with
      repetitive ankle sprains (RASs) and eleven healthy taekwondo athletes (the
      controls) at the college level participating in taekwondo training sessions. For
      the controls, the "injured" limb was taken to be the left limb. [Results] The
      postural stability measured in both the anteroposterior and mediolateral
      directions using center-of-pressure variables was lower in the uninjured limb of
      the RAS group than in the control group during a single-leg stance with eyes
      closed. However, for the injured limb, there were no significant differences
      between the two groups. Furthermore, compared to the RAS group, the control group
      had higher stability in the injured limb than in the uninjured limb. [Conclusion]
      Individuals with RASs should ensure improvements in their proprioceptive and
      neuromuscular functions, as well as muscle strength, through an adequate period
      of rehabilitation to reduce the risk of re-injury.

PMID- 29581661
TI  - Effects of thoracic posture correction exercises on scapular position.
AB  - [Purpose] The purpose of this study was to investigate the effects of thoracic
      extension exercise on scapular alignment and thoracic kyphosis angle. [Subjects
      and Methods] Ten subjects with a kyphosis angle >=40 degrees  and aged between 20
      and 26 years participated in this study. This study investigated the scapular
      forward distance and thoracic kyphosis angle before and after the thoracic
      extension exercise. [Results] The kyphosis angle after exercise was significantly
      decreased compared with that before exercise. Scapular forward distance after
      exercise significantly decreased compared to that before exercise. [Conclusion]
      The results of the present study suggest that correction of thoracic kyphosis
      should be included among exercises designed to achieve normal scapular alignment.

PMID- 29581662
TI  - Relationship between advanced glycation end-product accumulation in the skin and
      pulmonary function.
AB  - . [Purpose] This study aimed to evaluate the relationship between advanced
      glycation end-product accumulation and pulmonary function in a general population
      with normal spirometry results. [Subjects and Methods] A total of 201 subjects
      (mean age, 56 +/- 11 years; males, 58%) enrolled in this study. Subjects were
      classified into two groups (younger group [<65 years old] and elderly group [>=65
      years old]). Skin autofluorescence was assessed as an estimate of advanced
      glycation end-product. Forced vital capacity and forced expiratory volume in one
      second were measured using a spirometer, and the forced expiratory volume in one
      second/forced vital capacity ratio (FEV1/FVC) was calculated. [Results] Skin
      autofluorescence was not an independent factor associated with FEV1/FVC in the
      younger group, but both skin autofluorescence and pack-years of smoking were
      significant independent factors associated with FEV1/FVC in the elderly group.
      [Conclusion] Advanced glycation end-product accumulation, assessed by skin
      autofluorescence, is an independent factor negatively associated with FEV1/FVC in
      elderly people with normal spirometry results.

PMID- 29581663
TI  - The effect of gait speed and gait phase to the allocation of attention during
      dual task gait.
AB  - [Purpose] The purpose of this study was to determine the change of allocation of
      attention caused by a difference in gait phase and gait speed. We also determined
      the relationship between attentional demand and gait automaticity change caused
      by the gait speed alteration. [Subjects and Methods] Ten male participated.
      Participants were instructed to perform the probe reaction time (RT) task during
      treadmill walking in four different gait speed conditions (60%, 80%, 100%, and
      120% of preferred speed). Walking ratio in each gait speed conditions were
      calculated, and RTs and walking ratios were compared in each gait speed condition
      and in the single-support and double-support gait phase. [Results] RTs were
      significantly delayed with decline of gait speed. Walking ratio was significantly
      decreased in proportion of decrement of gait speed. There was no difference of
      gait phase between single-support and double-support phase. [Conclusion] This
      study showed that relationship between attentional load and deficit of gait
      automaticity. While gait phase didn't influence attentional demand, and this
      result showed the characteristics of treadmill gait.

PMID- 29581664
TI  - Effects of inspiratory muscle training on pulmonary functions and muscle strength
      in sedentary hemodialysis patients.
AB  - [Purpose] This study was conducted to evaluate the effect of Inspiratory Muscle
      Trainer (IMT) on respiratory muscle strength and pulmonary functions. [Subjects
      and Methods] Fifteen sedentary unemployed patients were recruited from both
      genders who received regular hemodialysis sessions from at least three months.
      Those patients received Threshold IMT program for 12 weeks. Pulmonary functions
      and respiratory muscle strength in form of (PImax) and (PEmax) were measured by
      electronic spirometry and digital pressure vacuum meter respectively.
      Additionally oxygen saturation was measured by Finger pulse oximeter. All
      measurements were performed before and at the end of the treatment program after
      12 weeks. [Results] The results of this study revealed significant improvement in
      FVC%, FEV1%, PEF%, PImax and PEmax after three months of treatment by using
      inspiratory muscle trainer while no significant difference was recorded regarding
      to FEV1/FVC% ratio and SpO2. [Conclusion] Inspiratory muscle trainer is an
      effective therapeutic technique to improve respiratory muscle strength and
      pulmonary functions in patients undergoing hemodialysis.

PMID- 29581665
TI  - Effect of physical activity on cognition and daily living activities of the
      elderly with mild dementia.
AB  - [Purpose] The purpose of this study was to examine the effects of a physical
      activity program on cognitive function and ADLs in elderly people with mild
      dementia. [Subjects and Methods] Both groups (n=60) participated in a cognition
      program three times a week for 30 minutes each time over an eight-week period. In
      addition, the experimental group (n=30) underwent a physical activity program for
      30 minutes three times a week over an eight-week period. The LOTCA-G and the FIM
      were recorded in both groups before and after the experiment to evaluate changes
      in their cognition and ADLs. [Results] The experimental group showed significant
      results in 18 subtests and total LOTCA-G, while the control group exhibited
      significant results in 8 subtests and total LOTCA-G. The comparison results
      between groups before and after the intervention are as follows. The experimental
      group showed significant results in 15 subtests and FIM total, while the control
      group exhibited significant results in 7 subtests and FIM total. The comparison
      results between groups before and after the intervention are as follows:
      significant results were revealed in 10 subtests and FIM total. [Conclusion] The
      physical activity program improves cognitive function and ADLs in patients with
      mild dementia.

PMID- 29581666
TI  - Lumbar lordosis angle and trunk and lower-limb electromyographic activity
      comparison in hip neutral position and external rotation during back squats.
AB  - [Purpose] To compare the lumbar lordosis angle and electromyographic activities
      of the trunk and lower-limb muscles in the hip neutral position and external
      rotation during back squats. [Subjects and Methods] Ten healthy males without
      severe low back pain or lower-limb injury participated in this study. The lumbar
      lordosis angle and electromyographic activities were measured using three
      dimensional motion-capture systems and surface electrodes during four back
      squats: parallel back squats in the hip neutral position and external rotation
      and full back squats in the hip neutral position and external rotation. A paired
      t-test was used to compare parallel and full back squats measurements in the hip
      neutral position and external rotation, respectively. [Results] During parallel
      back squats, the average lumbar lordosis angle was significantly larger in hip
      external rotation than in the hip neutral position. During full back squats,
      lumbar erector spinae and multifidus activities were significantly lower in hip
      external rotation than in the hip neutral position, whereas gluteus maximus
      activity was significantly higher in hip external rotation than in the hip
      neutral position. [Conclusion] The back squat in hip external rotation induced
      improvement of lumbar kyphosis, an increasing of the gluteus maximus activity and
      a decrease of both lumbar erector spinae and multifidus activities.

PMID- 29581667
TI  - Total assessment-reassessment & evaluation using bioKinesiologic (TAREK)
      approach: case presentation for theoretical formulation.
AB  - [Purpose] To introduce a new systematic physical therapy evaluation aiming to
      facilitate the process of examining complicated musculoskeletal cases. [Subject
      and Methods] The patient was a 20 years old male college student who had major
      motor vehicle accident one year ago. The patient was poorly responding to
      physical therapy and he felt that his case was worsening. The complexity of the
      case dictated a new evaluation with a different approach to resolve the barriers
      hindering the patient from showing functional improvements. [Results] The new
      evaluation approach explained many undetermined and stubborn symptoms experienced
      by the patient. The expert confirmed that the traditional evaluations methods
      utilized were insufficient to address patient's complaints. [Conclusion] Total
      Assessment-Reassessment & Evaluation using bioKinesiologic (TAREK) approach is
      comprehensive evaluation strategy using systematic pathway that guides clinicians
      to pinpoint the contribution of pathoanatomical structures in producing
      pathomechanical mobility and poor functional outcomes.

PMID- 29581668
TI  - Effects of task-specific paretic ankle plantar flexor training on walking in a
      stroke patient: a single-case study.
AB  - [Purpose] The purpose of this study was to examine the effects of task-specific
      plantar flexor training on walking ability indices in a patient with a paretic
      ankle. [Subject and Methods] The subject was a 65-year-old male patient with
      right hemiplegia due to a left medullary ventral infarction. An ABA' single
      subject design was adopted. The independent variable was a task-specific plantar
      flexor training exercise, similar to that during walking, targeting the paretic
      ankle. The dependent variables were the isometric ankle plantar flexor strength,
      maximum walking speed, step length, and trailing limb angle in the paretic
      terminal stance phase. The B study phase was divided into B1 and B2 phases. A two
      standard-deviation-band method was used to evaluate improvement. [Results]
      Improvements in the paretic plantar flexor strength, maximum walking speed, step
      length, and trailing limb angle in the B2 phase were observed. The improvements
      in the maximum walking speed, step length, and trailing limb angle were sustained
      in the A' study phase. [Conclusion] These results suggest that task-specific
      plantar flexor training exercise is efficacious in improving the walking ability
      index of a paretic ankle.

PMID- 29581669
TI  - Comparision of the effectiveness of ESWT and ultrasound treatments in myofascial
      pain syndrome: randomized, sham-controlled study.
AB  - [Purpose] The purpose of this study is to compare effectiveness of extracorporeal
      shock wave therapy (ESWT), ultrasound (US) and sham ESWT in the treatment of
      myofascial pain syndrome (MPS). [Subjects and Methods] Sixty MPS patients aged 18
      60 years were included in the study. The patients were randomized equally into 3
      groups. Group 1 received ESWT for 4 session with 3 day-intervals. Group 2
      received 4 sessions of sham ESWT. US was applied to Group 3 for 10 sessions. All
      patients were recommended an exercise program. The patients were evaluated before
      post and 6 weeks after treatment. Measurements were made using pressure pain
      threshold (PPT), pain score (PS) and visual analogue scale (VAS). Patients were
      evaluated by using SF-36 and HADS (hospital anxiety and depression scale).
      [Results] A significant posttreatment difference was found in VAS, PPT and SF-36
      subparameters in group 1. In group 2, a significant difference was not found in
      any parameter. In group 3, a significant difference was detected in parameters of
      VAS and PPT. A significant difference was found between groups 1 and 2 as for
      subtitles of PPT, VAS, SF-36. [Conclusion] These results suggest that ESWT is as
      effective as US. ESWT and US are significantly more effective than sham ESWT.

PMID- 29581670
TI  - Effects of chin tuck exercise using neckline slimmer device on suprahyoid and
      sternocleidomastoid muscle activation in healthy adults.
AB  - [Purpose] This study investigated the effect of chin tuck exercise (CTE) using a
      neckline slimmer device on suprahyoid (SH) and sternocleidomastoid (SCM) muscle
      activation in healthy adults. [Subjects and Methods] We measured activation of
      the SH and SCM muscles using surface electromyography in 20 healthy adults during
      head lift exercise (HLE) and CTE using a neckline slimmer device. The order of
      exercises was randomized and the mean and peak values of each muscle's activation
      were assessed. [Results] During the CTE using a neckline slimmer device, SH
      activation was significantly greater and SCM activation was significantly lower
      than during the HLE. [Conclusion] This study suggest that chin-tuck exercise
      using a neckline slimmer device may be more helpful than HLE for swallowing
      training.

PMID- 29581671
TI  - Effects of lumbar lordosis assistive support on craniovertebral angle and
      mechanical properties of the upper trapezius muscle in subjects with forward head
      posture.
AB  - [Purpose] The aim of this study was to investigate the effect of lumbar lordosis
      assistive support (LLAS) on craniovertebral angle (CVA) and mechanical properties
      of the upper trapezius (UT) muscle in subjects with forward head posture (FHP).
      [Subjects and Methods] This study recruited 20 subjects with FHP. CVA and muscle
      tone, viscoelasticity, and stiffness of the UT were measured using Myoton in all
      subjects in a sitting position with LLAS and in a neutral sitting position. The
      order of measurements was randomized and the mean values were calculated twice.
      [Results] The sitting position with LLAS showed a significantly greater
      improvement than the neutral sitting position with regard to CVA and muscle tone,
      viscoelasticity, and stiffness of the UT. [Conclusion] We suggest that the
      sitting position using LLAS induces the maintenance of normal neck posture and a
      reduction in the muscle tone of the UT in the subjects with FHP.

PMID- 29581672
TI  - Foot pressure analysis of gait pattern in older Japanese females requiring
      different personal care support levels.
AB  - [Purpose] This study evaluated gait parameters and foot pressure in two regions
      of the feet among older females with different personal care support needs to
      analyze factors that contribute to higher support requirements. [Subjects and
      Methods] Thirty-two older females were divided into support-need and care-need
      level groups. Gait parameters (speed, cadence, step length, step width, gait
      angle, toe angle, double support phase, swing phase, and stance phase) and foot
      pressure during a 5-m walk were measured and analyzed in the two groups.
      [Results] The percentage of the double support phase on both feet and the right
      stance phase were significantly higher in the care-need level group, while that
      of the right swing phase was significantly lower than that of the support-need
      level group. Additionally, the phase showing peak pressure on the left rear foot
      was significantly delayed and the left forefoot pressure in the terminal stance
      was significantly lower in the care-need level group than in the support-need
      level group. [Conclusion] These findings show that the temporal duration
      parameters and foot pressure on a particular side were significantly different
      between the two groups and suggest that these differences were associated with a
      higher care level.

PMID- 29581673
TI  - Changes in exercise tolerance and quality of life are unrelated in lung cancer
      survivors who undergo video-assisted thoracic surgery.
AB  - [Purpose] The associations between changes in respiratory function, exercise
      tolerance, and quality of life (QOL) in patients with lung cancer who undergo
      lobectomy using video-assisted thoracoscopic surgery (VATS) are unclear. This
      study aimed to investigate the relationships between exercise tolerance and QOL
      in patients who underwent VATS. [Subjects and Methods] Thirty-six patients with
      lung cancer were followed for 3 months after VATS. Patients were evaluated before
      and 1, 4, and 12 weeks after surgery. Respiratory function, grip strength, and
      knee extension strength, as well as the results of timed up and go, 6-minute
      walk, and cardiopulmonary exercise tests, were evaluated using the 36-item short
      form health survey. Longitudinal changes in physical performance and QOL were
      analyzed, as was the relationship between the change in physical function and
      QOL. [Results] The physical and social aspects of QOL significantly decreased at
      week 4 post-surgery, but recovered to pre-surgical levels by week 12. In
      contrast, physical (non-respiratory) function recovered to pre-surgical levels by
      week 4. There was no correlation between the percentages of change in QOL and
      those related to physical function. [Conclusion] Our preliminary study highlights
      the fact that early recovery of physical function is possible after VATS, but
      does not necessarily correlate with early QOL recovery. It is therefore necessary
      to perform perioperative interventions to promptly restore QOL after surgery.

PMID- 29581674
TI  - Novel method for evaluation of hindfoot alignment in weight-bearing position
      using laser beam.
AB  - [Purpose] It is clinically important to accurately evaluate the alignment of
      hindfoot alignment from the body surface in weight-bearing position. In general,
      measurement is carried out using a goniometer, but the measurement with
      goniometer requires experience, and the reliability in this measurement is also
      in question. Therefore, it is necessary to establish a clinical measurement
      method to replace the goniometer. As a solution, we devised a hindfoot alignment
      measurement method with laser beam (HAML), which measures hindfoot alignment
      along the body surface using a laser beam. This study aimed to study the
      correlation between the measurement result along the body surface with laser or
      goniometer and that of radiography with regard to hindfoot alignment. [Subjects
      and Methods] Subjects included 23 individuals with knee osteoarthritis. Their
      hindfoot alignment using radiography and goniometry were measured. The
      correlation between the measurement result along the body surface with or without
      laser and radiography was investigated. [Results] The correlation between HAML
      and radiography was better than that between HAML and goniometry. [Conclusion]
      The correlation between radiography and HAML for measuring hindfoot alignment was
      good. This finding implies that HAML can be used as a screening test or
      epidemiological survey in regional medicine.

PMID- 29581675
TI  - The effects of pain scrambler therapy on the pain and quality of life of
      degenerative gonarthritis patients.
AB  - [Purpose] The purpose of this study was to identify the effects of pain scrambler
      therapy on the pain and quality of life of degenerative gonarthritis patients.
      [Subject and Methods] This study is a single case study. Pain scrambler therapy
      was applied for 40 minutes per session once a day for 15 days to a 62-year-old
      female patient diagnosed with degenerative gonarthritis. Pain was measured using
      the Visual Analogue Scale and quality of life was measured using the short form
      36 item after therapy. [Results] Decrease in pain and improved quality of life
      were evident after pain scrambler therapy. [Conclusion] Pain scrambler therapy
      had a potential to decrease pain and improve the quality of life in degenerative
      gonarthritis patients.

PMID- 29581676
TI  - Choosing Wisely in Surgery-a Perspective from the UK.

PMID- 29581677
TI  - Laparoscopic-Assisted Transhiatal Esophagectomy (LATE) for Carcinoma of the
      Esophagus.
AB  - Total laparoscopic approach for the management of carcinoma of the esophagus has
      not gained much popularity due to its complexity. The aim of this study was to
      evaluate safety, feasibility, and outcome of laparoscopic-assisted transhiatal
      esophagectomy (LATE) for patients with carcinoma of the esophagus. This
      retrospective study involves a total of 26 patients with carcinoma of the
      esophagus who were considered for LATE by a single surgical team from January
      2010 to September 2014. The median (range) age was 55 years (35-72), and male to
      female ratio was 20:6. The median (range) operative time, blood loss, and
      hospital stay were 300 min (180-660), 300 ml (100-500), and 11.5 days (8-25),
      respectively. Pulmonary complications and cervical anastomotic leak (including
      one patient with conduit necrosis) occurred in eight (30.7 %) and three (11.5 %)
      patients, respectively. AJCC stage (7th ed.) was IIA in 12 (46.15 %), IIB in 10
      (38.46 %), IIIA in 3 (11.53 %), and IIIB in 1 (3.84 %) patient. Surgical
      resection margin was negative in all but one patient (3.8 %). The median (range)
      number of lymph nodes (LN) retrieved was 13 (8-28). During a median follow-up 19
      months (8-39), five patients (19.23 %) developed recurrence and three (11.5 %) of
      them died. LATE is a safe and feasible for the management of selected patients
      with carcinoma of the lower thoracic esophagus.

PMID- 29581678
TI  - Ten-Year Experience of Managing Giant Duodenal Ulcer Perforations with Triple
      Tube Ostomy at Tertiary Hospital of North India.
AB  - Duodenal ulcer perforations have been known since 1600 AD. It is a common
      surgical emergency and every surgeon will encounter it. The perforation size of
      >2 cm has been used as the criteria for defining Giant duodenal ulcers. The
      management of giant duodenal perforations in hemodynamically unstable patient
      with comorbid condition is taxing because of high incidence of the postoperative
      leak and mortality. We have used the simple technique of Triple Tube Ostomy after
      the primary closure of the defect with encouraging results. It is a retrospective
      study done at the J. N medical college AMU Aligarh from May 2005 to May 2015.
      Hemodynamically unstable patients who have presented to the emergency with
      preoperative diagnoses of giant duodenal ulcer perforation and had undergone
      triple tube ostomy with primary repair of the perforation were included in the
      study. There were 34 patients of giant duodenal perforation who presented in
      shock. All of them underwent triple-tube-ostomy after primary repair of the
      duodenum. Thirty-two patients recovered with two mortalities (5.8 %). Several
      definite surgical techniques have been described for the management of giant
      duodenal ulcer perforation but they are complex, have very high morbidity and
      mortality rate and require an expert surgeon. A close retrospective scrutiny of
      the patients suggests that simple triple-tube-ostomy technique which is based on
      the principle of damage control surgery has good postoperative results Therefore,
      we recommend it as the procedure of choice in these patients.

PMID- 29581679
TI  - Balloon-Inflated Catheters for Enteral Feeding: a Word of Caution.
AB  - Catheters with inflatable balloons such as a Foley catheter may be used for
      feeding gastrostomy/jejunostomy. The incorrect or improper use of these catheters
      can have serious consequences. We report 13 cases of feeding jejunostomy with
      balloon-inflated catheter's malfunction, some referred to our centre and others
      operated here over a period of 8 years. The most dramatic consequence of such
      improper use led to rupture of the small intestine due to inadvertent over
      inflation (over 100 ml) of the balloon of the catheter during a contrast study.
      The patient required a laparotomy with resection and anastomosis of the bowel.
      Three other patients had similar over-inflation of the balloon leading to severe
      pain and discomfort. In all three patients, timely deflation of the balloon was
      sufficient to relieve the symptoms. One patient had intussusception with the
      inflated balloon acting as a lead point. The patient underwent resection of the
      small bowel with end jejunostomy and distal mucous fistula. All other patients
      presented with abdominal pain and distension and intestinal obstruction and were
      managed non-operatively with deflation of balloon either by aspiration, cutting
      the balloon port or ultrasound-guided puncture of balloon. Healthcare personnel
      dealing with patients with indwelling catheters must be educated to suspect,
      detect and manage such problems. The best measure for such unusual complications
      of otherwise safe devices would be prevention by training and generation of
      awareness.

PMID- 29581680
TI  - Sexuality in Surgically Treated Carcinoma Penis Patients and Their Partners.
AB  - Most common treatment offered to carcinoma penis patients is surgery. This
      results in not only mutilation of the genitals but also affects their sexuality.
      The treating physician fails to address the issue due to the paucity of the data
      in this regard. Hence, we decided to evaluate sexuality in these patients after
      surgical treatment for penile cancer. Most of the times, their partners also face
      problems of sex and sexuality, regarding which there is no literature. Hence, we
      decided to include their partners also in the study. We retrieved records of the
      patients who underwent surgical treatment for carcinoma penis at our institute.
      After obtaining ethical committee approval, they were invited along with their
      partners for personal interview. After obtaining written informed consent from
      each of them, they were administered sexual functioning questionnaire (SFQ).
      Sexuality was evaluated based on the scores obtained. Performance anxiety was
      reported by majority of these patients. Their sexual interest, arousal and desire
      remained almost intact with reduction in satisfaction more so in total
      penectomised patients. Though the partners had accepted the global reduction in
      sexuality as their fate, their interpersonal relationship remained little
      disturbed. The study reveals that sexuality is more than the sexual intercourse
      alone. Proper pre-operative counselling of these patients and their partners by
      the treating urologist helps better post-treatment adjustment with regards to
      sexuality in these patients as well as their partners.

PMID- 29581681
TI  - Robot-Assisted Mckeown Esophagectomy is Feasible After Neoadjuvant
      Chemoradiation. Our Initial Experience.
AB  - Neoadjuvant chemoradiation has become the standard of care for esophageal cancer,
      especially for middle third esophageal lesions and those with squamous histology.
      Although more and more thoracic surgeons and surgical oncologists have now
      shifted to video-assisted and robot-assisted thoracoscopic esophagectomy; there
      is still limited experience for the use of minimal-assisted approaches in
      patients undergoing surgery after neoadjuvant chemoradiation. Most surgeons have
      concerns of feasibility, safety, and oncological outcomes as well as issues
      related to difficult learning curve in adopting robotic esophagectomy in patients
      after chemoradiation. We present our initial experience of Robot-Assisted Mckeown
      Esophagectomy in 27 patients after neoadjuvant chemoradiation, from May 2013 to
      October 2014. All patients underwent neoadjuvant chemoradiation to a dose of 50.4
      Gy/25Fr with concurrent weekly cisplatin, followed by reassessment with clinical
      examination and repeat FDG PET/CT 6 weeks after completion of chemoradiation.
      Patients with progressive disease underwent palliative chemotherapy while
      patients with either partial or significant response to chemoradiation underwent
      Robot-Assisted Mckeown Esophagectomy with esophageal replacement by gastric
      conduit and esophagogastric anastomosis in the left neck. Out of 27 patients,
      92.5 % patients had stage cT3/T4 tumours and node-positive disease in 48.1 % on
      imaging. Most patients were middle thoracic esophageal cancers (23/27), with
      squamous histology in all except for one. All patients received neoadjuvant
      chemoradiation and subsequently underwent Robot Assisted Mckeown Esophagectomy.
      The average time for robot docking, thoracic mobilization and total surgical
      procedure was 13.2, 108.4 and 342.7 min, respectively. The procedure was well
      tolerated by all patients with only one case of peri-operative mortality. Average
      ICU stay was 6.35 days (range 3-9 days). R0 resection rate of 96.3 % and average
      lymph node yield of 18 could be achieved. Pathological node negativity rate (pN0)
      and complete response (pCR) were 66.6 and 44.4 %, respectively. In the initial
      cases, four patients had to be converted to open due technical reasons or
      intraoperative complications. The present study, with shorter operative times,
      similar ICU stay, overall low morbidity, and mortality and optimal oncological
      outcomes suggest that robot-assisted thoracic mobilization of esophagus in
      patients with prior chemoradiation is feasible and safe with acceptable
      oncological outcomes. It has a shorter learning curve and hence allows for a
      transthoracic minimally invasive transthoracic esophagectomy to more and more
      patients, otherwise unfit for conventional approach.

PMID- 29581682
TI  - Comparing Hemodynamic Symptoms and the Level of Abdominal Pain in High- Versus
      Low-Pressure Carbon Dioxide in Patients Undergoing Laparoscopic Cholecystectomy.
AB  - The laparoscopic cholecystectomy (LC) is the gold standard to treat gallstone. To
      view the surgical site in this type of operations better, carbon dioxide is used
      with a certain pressure. The current study aimed to compare the hemodynamic
      symptoms and the level of abdominal pain due to using high- and low-pressure
      carbon dioxide in patients undergoing LC. The current double-blind randomized
      clinical trial was conducted on 60 patients with the age range of 20-70 years old
      undergoing LC. The first and second groups experienced PaCO2 of 7-10 and 12-14
      mmHg, respectively. The hemodynamic symptoms, abdominal pain, shoulder-tip pain,
      nausea and vomiting after the surgery, and the mean of liver function tests were
      evaluated. Data were analyzed using T test, Chi-square test, and repeated
      measures ANOVA by SPSS 16. Information of 60 patients in two groups was analyzed.
      There was a significant difference between the groups regarding the mean of
      systolic blood pressure (P < 0.05). The mean of heart rate was significantly
      higher in the high-pressure group during surgery and 1 h after that (P < 0.05).
      The frequency of pain in shoulder-tip and abdomen was higher in the high-pressure
      group. Frequency of nausea and vomiting 12 h after the surgery between two groups
      was significant (P < 0.05). The mean of alkaline phosphatase was higher in the
      low-pressure group than the high-pressure group (P < 0.05). Considering the good
      performance and low side effects of low-pressure laparoscopic cholecystectomy
      compared to those of high-pressure, this method can be replaced by high-pressure
      in LC.

PMID- 29581683
TI  - An Analysis of Presentation, Pattern and Outcome of Chest Trauma Patients at an
      Urban Level 1 Trauma Center.
AB  - Chest trauma is an important public health problem accounting for a substantial
      proportion of all trauma admissions and deaths. It directly account for 20-25 %
      of deaths due to trauma. Therefore, this study was conducted to analyze the
      presentation, patterns, and outcome of chest trauma in a level-1 urban trauma
      center. It was a prospective observational study of all patients presented with
      chest trauma to an urban level 1-trauma center over a period of 3 years.
      Demographic profile, mechanism of injury, injury severity scores (ISS),
      associated injuries, hospital stay, etc. were recorded. Morbidity and mortality
      rates were analyzed and compared with the published literature. Chest injuries
      comprised 30.9 % of all trauma admissions and the mechanism was blunt in majority
      (83.5 %) of the cases. Vehicular crashes (59.7 %) followed by assault were the
      most common modes of injury. Rib fracture was the most common chest injury seen
      in 724 of the 1258 patients while abdominal visceral injuries were the commonest
      associated injuries in polytrauma cases. Majority of the patients were managed
      non-operatively. Inter costal tube drainage (ICD) was the main stay of treatment
      in 75 % of the cases, whereas, thoracotomy was required only in 5.56 % of the
      patients. Overall mortality was 11 % and it was found to be significantly higher
      following blunt chest trauma. We observed that associated extra thoracic injuries
      resulted in higher mortality as compared to isolated chest injuries. Thoracic
      injuries can be readily diagnosed in the emergency department by meticulous and
      repeated clinical evaluation and majority require simple surgical procedures to
      prevent immediate mortality and long-term morbidity.

PMID- 29581684
TI  - Robotic Pancreaticoduodenectomy: Single-Surgeon Initial Experience.
AB  - Minimally invasive surgery has gained increasing acceptance over the last few
      years, which has expanded to pancreaticoduodenectomy. Laparoscopic
      pancreaticoduodenectomy has been determined to be a feasible, safe, and effective
      procedure in an experienced surgeon's hands, but the adaptations to the clumsy
      instruments are needed. The improved dexterity of the Da Vinci robotic system
      provides a good opportunity to perform this challenging procedure in the
      minimally invasive context. The aim of this study was to share our preliminary
      experience of totally robotic pancreaticoduodenectomy. From April 2015 to August
      2015, four patients were selected to undergo totally robotic
      pancreaticoduodenectomy in the Department of Pancreatic Surgery, West China
      Hospital, Sichuan University, China. The demographic characteristics,
      perioperative details, and pathological results were retrospectively reviewed.
      One female and two male patients underwent totally robotic
      pancreaticoduodenectomy, while another male patient underwent robotic total
      pancreatectomy due to the severe atrophy of pancreatic body and tail. The mean
      age of the four patients was 56.8 years. The average operation time and
      intraoperative blood loss were 563 min and 228 mL, respectively. No one needed
      blood transfusion, conversion to open pancreaticoduodenectomy, or postoperative
      analgesia. The postoperative courses of these patients were uneventful. The mean
      postoperative hospital stay was 10 days. No one required to be readmitted, and
      there was no death within 30 days following the surgery. Final pathologic
      examinations revealed one malignant pancreatic ductal adenocarcinoma, and three
      benign lesions. Based on this initial study, robotic pancreaticoduodenectomy is
      safe and feasible, with acceptable oncological outcomes for highly selected
      patients in experienced surgeons' hands. However, concerns such as long-term
      outcomes, cost-effectiveness analysis, and learning curve analysis should be
      fully demonstrated before the popularization of this challenging procedure.

PMID- 29581685
TI  - Incidental Findings in Routine Histopathological Examination of Appendectomy
      Specimens; Retrospective Analysis of 1970 Patients.
AB  - Diseases and tumors of the appendix vermiformis are very rare, except for acute
      appendicitis. This study aimed to examine rare findings in the histopathologic
      examinations of specimens of patients undergoing appendectomy due to the
      diagnosis of acute appendicitis. The files of 1970 patients undergoing
      appendectomy due to the diagnosis of acute appendicitis between March 2012 and
      March 2016 were retrospectively investigated. Rare findings were found in 59 (3
      %) patients, and these were evaluated in detail. Patients' age, gender, pathology
      reports, and postoperation follow-ups were recorded. The rare histopathological
      findings of 59 patients were examined. Of these, 31 were female (52.5 %) and 28
      were male (47.5 %). The average age was 33.1 +/- 18.2 years. The unusual findings
      were as follows: 16 fibrous obliteration, 11 Enterobius vermicularis, 2
      schistosomiasis, 3 appendiceal neuroma, 2 granulomatous appendicitis, 1 Crohn's
      disease, 3 chronic appendicitis, 1 endometriosis, 2 hyperplastic polyps, 9
      mucinous cystadenoma (+mucocele), 8 carcinoid tumors, and 1 lymphoma. All of the
      malignant tumors were localized in the distal end of the appendix, and all of the
      patients were treated with appendectomy. Patients with parasitic diseases also
      underwent anthelmintic treatment, while chemotherapy was administered to the
      patient with lymphoma. All of the patients diagnosed with malignancy were alive
      reported no problems at their follow-ups. Although all of the appendectomy
      samples were normal macroscopically, data from this study suggest that all
      specimens should be sent for routine investigation.

PMID- 29581686
TI  - The Charlson Comorbidity Index as an Independent Prognostic Factor in Older
      Colorectal Cancer Patients.
AB  - High-age patients have higher rates of comorbidity that are associated with a
      poor prognosis. It is important to correctly evaluate their preoperative status
      to avoid mortality. The aim of this study was to clarify whether the Charlson
      comorbidity index (CCI) was useful for predicting postoperative outcomes. This
      retrospective study collected data from 250 consecutive patients over 75 years of
      age. The CCI takes into account 19 comorbid conditions. Inflammation-based
      scores, including the Glasgow prognostic score (GPS) and the platelet to
      lymphocyte ratio (PLR), are other preoperative scoring systems. The relationships
      among these scores and postoperative outcomes were evaluated. The patients were
      classified according to their vital status (dead, n = 30 or alive, n = 220).
      Comorbidities, the presence of double cancer, and lymph node metastases were
      significantly different between the groups (p < 0.01, p = 0.01, and p < 0.01). In
      regard to the scoring systems, the CCI, GPS, and PLR were significantly different
      (p = 0.02, p = 0.03, and p = 0.05). Multivariate analysis identified CCI >= 2
      (hazard ratio (HR) = 5.24, 95 % confidence interval (CI) = 1.30-12.1, p = 0.01)
      as a significant determinant of postoperative outcome (p < 0.01). The overall
      survival tended to be lower in patients with high CCI scores group (p = 0.03).
      The CCI was useful to predict postoperative outcomes in high-age colorectal
      cancer patients.

PMID- 29581687
TI  - Efficacy of the Evaluation of Inflammatory Markers for the Reduction of Negative
      Appendectomy Rates.
AB  - Unnecessary appendectomy can cause complications; ways of reducing negative
      appendectomy rates (NAR) using biochemical and imaging methods are desirable. We
      retrospectively examined 640 patients who underwent appendectomy for suspected
      AA. Patients with histologically confirmed appendicitis were designated the
      positive appendectomy group (n = 565), whereas those with unconfirmed
      appendicitis were designated the negative appendectomy group (n = 75). The
      positive appendectomy group was subdivided into the non-perforated (n = 511) and
      perforated (n = 54) appendectomy groups according to pathology reports. We
      compared the age, sex, lymphocyte count, neutrophil percentage, pathologic
      positivity or negativity for appendicitis, C-reactive protein (CRP) level,
      neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) of
      the patients. When the perforated, non-perforated, and negative appendectomy
      groups were compared, the highest CRP level, NLR, and PLR were evident in the
      perforated appendectomy group (p = 0.001), whereas the lowest neutrophil
      percentage was found in the non-perforated appendectomy group (p = 0.001).
      Multiple logistic regression analysis identified neutrophil percentage, CRP
      value, and NLR as independent variables and demonstrated that AA could be
      diagnosed with 88.9 % accuracy using the cutoff values determined. In patients
      with suspected AA, particularly in rural areas with limited access to advanced
      imaging modalities, the evaluation of neutrophil percentage, CRP level, and NLR,
      in combination with the findings of a physical examination, may aid diagnosis and
      reduce NAR.

PMID- 29581689
TI  - Synchronous Squamous Cell Carcinoma of the Anorectum and Proctosigmoid-a Case
      Report.
AB  - Primary squamous cell carcinoma of the rectum is extremely rare. Squamous cell
      carcinoma of the anorectum is a known entity evaluation and treatment protocols
      have been well defined. The occurrence of squamous cell carcinoma of rectosigmoid
      in concurrence with squamous cell carcinoma of the anal canal is extremely rare
      and the first case to be reported in the literature. A 48-year-old male patient
      presented with difficulty in passing stools. The clinical examination,
      colonoscopy, and the histopathology revealed synchronous proctosigmoid and the
      anorectal neoplasm. A case like this will pose a diagnostic challenges; squamous
      cell carcinoma of the rectum is not defined in the medical literature;
      synchronous squamous cell carcinoma will pose both diagnostic dilemmas and
      treatment challenges like whether to conserve the sphincter or not. Because
      squamous cell carcinoma of the anorectum can be treated by chemoradiotherapy,
      even this case is initially thought of treating by neoadjuvant chemoradiotherapy
      followed by low anterior resection followed by adjuvant treatment. Since there
      was no medical literature to support this treatment, ultimately multidisciplinary
      tumor board decision was made for abdominoperineal resection. Patient was treated
      with abdominoperineal resection and adjuvant chemoradiation. The diagnostic
      dilemmas and the management issues have been discussed.

PMID- 29581688
TI  - Introducing In Vivo Dissection Modules for Undergraduate Level Trainees: What Is
      the Actual Benefit and How Could We Make It More Efficient?
AB  - Essential Skills in the Management of Surgical Cases (ESMSC) is an international
      wet lab simulation course aimed at undergraduate students. It combines basic
      science workshops, case-based lectures and ex vivo skills modules, as well as in
      vivo dissections using a swine model. This study aims to evaluate the
      effectiveness of high-fidelity In Vivo Simulation-Based Learning for
      undergraduate level trainees. Also our goal was to compare the skill-based
      performance of final year students vs. more junior-level ones. Forty
      undergraduate delegates at clinical rotation level (male = 28, female = 12, mean
      age = 23.12, 22-24, SD = 0.69) attended this 2-day course in Athens. N = 1 (2.5
      %) was year 3, N = 4 (10 %) were year 4, N = 23 (57.5 %) were year 5 and N = 12
      (30 %) were year 6. N = 30 (75 %) came from Hellenic universities, N = 8 (20 %)
      from the UK and N = 2 (5 %) from Germany. N = 20 (50 %) attended the in vivo
      dissections module first, and then the ex vivo one (type A rotation), whereas N =
      20 followed the reverse training sequence with the ex vivo dissection first,
      followed by the in vivo one (type B rotation). The mean global rating scores for
      type A rotation were better in both the in vivo by 0.10 (2.40 vs. 2.30) and ex
      vivo modules by 0.15 (2.85 vs. 2.70), though it did not reach statistical
      significance (p > 0.05). Furthermore, the mean improvement of performance, in the
      laparoscopic skills station for the type A rotation, was better compared to type
      B by 0.351 (2.00 vs. 1.65, p = 0.003). Year 6 students performed better in the
      laparoscopic station (2.00 vs. 1.75, p = 0.059), whereas years 3, 4 and 5
      performed better in the in vivo (2.42 vs. 2.16, p = 0.157) as well as the ex vivo
      dissections (2.78 vs. 2.75, p = 0.832), though none of those comparisons reached
      statistical significance. Delegates seemed to appreciate and enjoy the in vivo
      dissections as reflected in the feedback (8.67/10, min = 6 and max = 10, SD =
      1.79). Although medical students seem to appreciate in vivo dissections modules,
      currently, further evidence is needed to support their recommendation in the
      undergraduate level. Surgical skills should be part of the undergraduate
      curriculum to improve final year students' performance in the theatre.

PMID- 29581690
TI  - Mentoring in Surgery-Mentor, Parshuram, Dronacharya, Krishan.
AB  - Success in any profession has no well-defined predictors. Knowledge, skills,
      training, and talent come in plenty but fail at times to achieve the universal
      goal of success. Some attribute it to luck. Apart from the tangible ingredients
      of a successful career, the intangibles like luck or something ill-defined is a
      real challenge. The intangibles seem like a chasm, an abyss, or a phantom
      obstacle. Presence of a guiding spirit who can handhold you to overcome these is
      essential for success. The aim of a professional is to learn, earn, and yearn for
      creativity. Practice of surgery is an ideal career to pursue the learning,
      earning, and yearning. More than any other profession, the guiding handholding
      spirit is required in surgical profession, the concept of mentoring. Originating
      from the Greco-Roman times when kind Odysseus left his son Telemachus under the
      care of his friend, mentor, it has become a universal defining necessity for a
      successful career in surgery. Indian history replete with such examples of
      mentorship, good as in the case of Dronacharya to Kaurvas but bad as denied by an
      able, competent, aspiring student like Eklavya. In the medical profession, there
      are very few Indian role models of mentorship. One name that comes to our mind is
      Dr. Krishan Mahajan. The more said is less revealed about him. "Knife before
      wife" was his commonly spoken advice to all who sought his mentorship. "Hard work
      is not easy but it is fair" so said a famous boxer, Larry Holmes. It is more than
      true for our profession as it is better to prepare and prevent, rather than
      repair and repent.

PMID- 29581691
TI  - Transmural Migration of Gossypiboma: a Rare Cause of Acute Abdomen.
AB  - Gossypiboma is the retained foreign body which is generally a cotton sponge/gauze
      after surgery. Incidence of gossypiboma is around one in 3000 to 5000 surgeries.
      This low incidence is mainly attributed to a low case reporting due to an
      associated medicolegal aspect. We are reporting a case of a 38 years old male,
      who presented with signs and symptoms of peritonitis. The patient had a history
      of open cholecystectomy 2 years back. A working diagnosis of perforation
      peritonitis was made, and the patient underwent exploratory laparotomy.
      Intraoperatively, a surgical sponge was present inside the ileal lumen causing
      intestinal obstruction with dense adhesion of bowel loops proximal to the site of
      obstruction with multiple ileal perforations. Even though the incidence of
      gossypiboma is very low, it should always be kept in mind as a cause of chronic
      abdominal pain and abdominal discomfort in a patient with previous abdominal
      surgery.

PMID- 29581692
TI  - Rupture of Cystic Artery Pseudoaneurysm: a Rare Complication of Acute
      Cholecystitis.
AB  - Pseudoaneurysm (PA) of the cystic artery is rare. Most of the reported cases are
      iatrogenic and develop secondary to liver biopsy, laparoscopic cholecystectomy,
      ERCP, and liver transplant. Other reported causes include trauma, malignancy,
      arteriovenous malformations, and inflammation in the hepatobiliary and pancreatic
      system. Cystic artery psuedoaneurysm is usually asymptomatic but may also present
      as vague abdominal pain, intra-abdominal mass, and hemobilia. In the event of
      rupture, it may present as a catastrophic intra-peritoneal bleeding with
      hemorrhagic shock. Doppler ultrasound and contrast-enhanced CT scan are useful
      tools for the diagnosis of this condition. However, selective visceral
      angiography is confirmatory and offers the opportunity for therapeutic
      embolization. We report a case which presented with upper right quadrant
      abdominal pain, vomiting, and hypotension. Abdominal ultrasonography revealed
      subhepatic hematoma and pericholecystic fluid collection along with acute
      calculus cholecystitis and sludge in the bile duct. Subsequent contrast-enhanced
      CT and CT angiography confirmed the presence of ruptured cystic artery
      psuedoaneurysm with subhepatic hematoma. The patient after resuscitation
      underwent selective visceral angiography and successful coil embolization of the
      cystic artery pseudoaneurysm. During the same admission, ERCP and biliary
      stenting were also performed followed by laparoscopic cholecystectomy. This case
      reports a rare entity which was successfully treated using a multimodality
      strategy.

PMID- 29581693
TI  - Large Solitary Plexiform Neurofibroma of the Penis Without Erectile Dysfunction:
      a Case Report from Kerala.
AB  - Case Report: Solitary plexiform neurofibroma of the penis is an extremely rare
      peripheral nerve lesion with only about 20 cases reported all around the world.
      Here, we are reporting a case of solitary penile plexiform neurofibroma with
      sexual dysfunction due to difficulty in penetration. This 47-year-old gentleman
      presented with a swelling on the dorsal side of the penis. He was aware of the
      swelling for the last 15 years. The swelling was slow growing and there was no
      associated loss of sensation or sexual dysfunction. For the last 2 months, he
      noticed that the tumour is rapidly increasing in size. He was also having
      difficulty in penetration during sexual intercourse which forced him to seek
      medical attention. He underwent excision of the swelling from our department.
      After 18 months of follow-up following excision, there has been no evidence of
      recurrence of the tumour. Conclusion: Penile plexiform neurofibromas are a rare
      type of lesions and are usually associated with neurofibromatosis. Solitary
      penile plexiform neurofibromas are extremely rare. Excision, when done properly,
      gives good results, without erectile dysfunction.

PMID- 29581694
TI  - Mayer-Rockitansky-Kuster-Hauser Syndrome Presenting as Irreducible Inguinal
      Hernia.
AB  - Inguinal hernia is the most common type of hernia experienced in the surgical OPD
      due to the muscular anatomy of the region being weak along with the natural
      weaknesses like deep ring with indirect hernia being more common than direct.
      Inguinal hernias may have varying unusual sac contents, a case presentation of
      rudimentary uterus and ovaries as contents of inguinal hernia in an adult female
      with Mayer-Rokitansky-Kuster-Hauser (MRKH) type II syndrome. This syndrome may be
      attributed to abnormal development of blastema of cervicothoracic somites and
      pronephriducts.

PMID- 29581695
TI  - Extreme Small Bowel Enteroatmospheric Fistula.
AB  - Small bowel enteroatmospheric fistula is a serious and devastating complication
      of open abdomen. We present an interesting image of a 40-year-old gentleman who
      developed multiple small bowel enteroatmospheric fistulae following open abdomen
      management for complicated intra-abdominal peritonitis.

PMID- 29581696
TI  - The "Christmas Tree" Sign on MR Cholangiogram in Left-Sided Cholangiohepatitis.
AB  - We report the "Christmas tree" sign on the magnetic resonance cholangiogram in
      two patients with left-sided cholangiohepatitis.

PMID- 29581697
TI  - Drain Tags: A Reliable Method of Securing Drains in the Neck.
AB  - Drains are essential in most surgeries. Primary need is elimination of dead space
      and related consequences but drains per se do have their share of complications,
      one of them being dislodgment. Complications related to dislodgment can range
      from inactive drains to damage to critical areas like anastomosis sites. Securing
      drains using this technique was described by Jayaraj et al. in 1988. Since then,
      no study was done to determine the efficacy and outcomes of this method. An audit
      was conducted from 2009 to 2014 at SDM Craniofacial unit to determine the utility
      of drain fixation. Data was collected of a total of 143 patients from the medical
      records. This useful technique has the advantage of preventing the drain from
      displacement and its consequent complications.

PMID- 29581698
TI  - Letter to "the Prevalence of Incidental Thyroid Carcinoma in Patients Who
      Underwent Thyroidectomy for Multinodular Goiter".

PMID- 29581699
TI  - Significant Points in Complicated Appendicitis.

PMID- 29581700
TI  - Red-Enhanced Photon Detection Module Featuring a 32 * 1 Single-Photon Avalanche
      Diode Array.
AB  - In this letter, the development and the experimental characterization of a new
      photon detection module, based on a 32*1 red-enhanced single-photon avalanche
      diode (RE-SPAD) array, are presented. A custom-developed technology has been
      exploited to design a detector having large-area pixels (50-um diameter) with
      optimized performance. With an excess bias voltage Voupsilon = 15 V, a photon
      detection efficiency as high as 57% at 600 nm (33% at 800 nm) is achieved, along
      with dark count rate in the kHz range and optical crosstalk probability as low as
      0.29%. The remarkable detection efficiency of the RE-SPAD array makes the module
      particularly suitable for all applications where high detection efficiency in the
      red/near-infrared range is mandatory. As an example, the performance of the array
      module is demonstrated to match the demanding requirements of multispot single
      molecule fluorescence spectroscopy.

PMID- 29581701
TI  - Thyroid Nodule Management: Thyroid-Stimulating Hormone, Ultrasound, and
      Cytological Classification System for Predicting Malignancy.
AB  - Background/objectives: Thyroid nodule (TN) is a common thyroid disorder globally,
      and the incidence has been increasing in recent decades. The objective of this
      study was to determine the contribution of thyroid-stimulating hormone (TSH),
      ultrasound (US), and cytological classification system for predicting malignancy
      among the surgically excised nodules. Design and methods: A retrospective
      analysis was performed between January 2012 and December 2014, using data drawn
      from 1188 patients (15-90 years), who had 1433 TN and fine-needle aspiration in
      Prince Sultan Military Medical City, Saudi Arabia. After reviewing all the
      thyroid cytopathological slides and US reports, classification was done based on
      the Bethesda System for Reporting Thyroid Cytology and the Thyroid Imaging
      Reporting and Data System (TI-RADS). Results: A total of 1188 patients' medical
      records were reviewed for this study, among them 311 patients had undergone
      surgical intervention (253 patients had single nodule and 58 had 2 nodules), with
      a total of 369 nodules. However, as 54 nodules on the US were either unavailable
      or unclear, the 315 remaining nodules were analyzed, revealing 30.2% (n = 95)
      malignancy overall. Patients with TSH values of >4.5 mIU/L (38.2%), TN <1 cm
      (48.8%), TI-RADS category 5 (75.6%), and Bethesda category VI (88.9%) revealed a
      higher percentage of malignancy. From the univariate analysis using the chi2
      test, significant relationship between the TSH, nodule size, TI-RADS, and the
      Bethesda category between the malignant and benign nodules emerged. The
      regression analysis showed that patients with a TSH value of 0.5 to 4.5 mIU/L
      (odds ratio [OR]: 2.96), TSH >4.5 mIU/L (OR: 6.54) had higher risk for malignancy
      than those with a TSH value of <=0.4 mIU/L. Thyroid nodules with sizes of 1 to
      1.9 cm (OR: 1.12), 2 to 2.9 cm (OR: 0.74), 3-3.9 cm (OR: 1.21), and >=4 cm (OR:
      0.52) were found to have no association with the risk of malignancy. Compared
      with TI-RADS 2 patients, those with categories 4B (OR: 1.35) and 5 (OR: 2.3) were
      found to be at higher risk of malignancy. Similarly, Bethesda IV (OR: 2.72), V
      (OR: 8.47), and VI (OR: 20; P < .02) category patients had a higher risk for
      malignancy than those in Bethesda class I. Among the study population, the
      papillary thyroid carcinoma was the most common type of thyroid cancer (86,
      90.5%) followed by 7.4% (n = 7) of follicular thyroid carcinoma, 1.05% (n = 1) of
      anaplastic carcinoma, and 1.05% (n = 1) of medullary thyroid carcinoma.
      Conclusions: A predictive model for risk of malignancy using a combining
      characteristic of the TSH, US, and cytological classification systems could
      assist the clinicians in minimizing exposing the patients with TNs to
      nonessential invasive procedures.

PMID- 29581702
TI  - Linear-In-Flux-Expressions Methodology: Toward a Robust Mathematical Framework
      for Quantitative Systems Pharmacology Simulators.
AB  - Quantitative Systems Pharmacology (QSP) modeling is increasingly used as a
      quantitative tool for advancing mechanistic hypotheses on the mechanism of action
      of a drug, and its pharmacological effect in relevant disease phenotypes, to
      enable linking the right drug to the right patient. Application of QSP models
      relies on creation of virtual populations for simulating scenarios of interest.
      Creation of virtual populations requires 2 important steps, namely,
      identification of a subset of model parameters that can be associated with a
      phenotype of disease and development of a sampling strategy from identified
      distributions of these parameters. We improve on existing sampling methodologies
      by providing a means of representing the structural relationship across model
      parameters and describing propagation of variability in the model. This gives a
      robust, systematic method for creating a virtual population. We have developed
      the Linear-In-Flux-Expressions (LIFE) method to simulate variability in patient
      pharmacokinetics and pharmacodynamics using relationships between parameters at
      baseline to create a virtual population. We demonstrate the importance of this
      methodology on a model of cholesterol metabolism. The LIFE methodology brings us
      a step closer toward improved QSP simulators through enhanced capture of the
      observed variability in drug and disease clinical data.

PMID- 29581703
TI  - Mental Health in School-Aged Children Prenatally Exposed to Alcohol and Other
      Substances.
AB  - Prenatal exposure to substances can possibly influence a child's neurodevelopment
      and may impact on subsequent mental health. We investigated the mental health
      status of school-aged children referred to a pediatric hospital with a history of
      prenatal exposure to alcohol or other substances. Mental health was assessed
      using the Strengths and Difficulties Questionnaire and compared with a reference
      group. A total of 105 of 128 (82%) eligible children prenatally exposed to
      substances participated in the study, with 48 children exposed to alcohol and 57
      to other substances. Strengths and Difficulties Questionnaire subscale mean
      scores, total difficulties scores, and total impact scores were statistically
      significantly higher in the group of exposed children, compared with the
      reference group. In this hospital-based population of school-aged children
      prenatally exposed to alcohol or other substances, the exposed group had an
      increased risk of mental health problems, compared with the reference group.

PMID- 29581704
TI  - Targeting Histone Demethylase LSD1/KDM1a in Neurodegenerative Diseases.
AB  - The autophagy-lysosome pathway sustains cellular homeostasis and is a protective
      mechanism against neurodegenerative diseases. Recent findings highlight the role
      of the histone demethylases LSD1/LDM1A as a pivotal regulator of autophagy
      process, by controlling the mTORC1 cascade, in neuroblastoma cells. LSD1 binds to
      the promoter region of the SESN2 gene, where LSD1-mediated demethylation leads to
      the accumulation of repressive histone marks that maintain SESN2 expression at
      low levels. LSD1 depletion results in enhanced SESN2 expression and consequently
      mTORC1 inhibition, thereby triggering the induction of autophagy. Our study
      provides important insight into neuroepigenetic mechanisms regulating the
      autophagic process, offering additional opportunities for the development of
      novel therapeutic strategies in diseases associated with dysfunctional autophagy
      lysosomal pathway.

PMID- 29581705
TI  - Hypoglycemic Coma in a Hemodialysis Patient Receiving Blood Glucose-Lowering
      Therapy With the Single Agent Teneligliptin.
AB  - Blood glucose management in patients undergoing dialysis is clinically
      challenging. In this population, most conventional oral hypoglycemic agents are
      contraindicated, especially from the perspective of pharmacokinetics. Dipeptidyl
      peptidase-4 inhibitors exert unique pharmacologic actions via glucose-dependent
      mechanism and have an excellent tolerability profile with a very low risk of
      hypoglycemia. Furthermore, the literature reports that some dipeptidyl peptidase
      4 inhibitors such as teneligliptin can be administered at the usual dose,
      regardless of a patient's level of renal impairment. In this article, we report a
      case of hypoglycemic coma with a blood glucose level of 23 mg/dL. The patient
      became fully conscious shortly after receiving a glucose injection; however,
      severe hypoglycemia recurred for approximately 1.5 days. It eventually
      disappeared on the discontinuation of teneligliptin, which was the only
      antidiabetic agent that he had received. The present case may provide deep
      insights into promoting the safe use of hypoglycemic agents in patients
      undergoing dialysis.

PMID- 29581707
TI  - Long noncoding RNA LINC01510 promotes the growth of colorectal cancer cells by
      modulating MET expression.
AB  - Background: Abnormal expression of long non-coding RNA (lncRNAs) often
      facilitates unrestricted growth of cancer cells. Long intergenic non-protein
      coding RNA 1510, an enhancer lncRNA (LINC01510), a lncRNA enhancer is upregulated
      in colorectal cancer (CRC), and its expression might relate to MET as revealed by
      lncRNA microarray data. However, the potential biological role of LINC01510 and
      its regulatory mechanism in CRC remain unclear. Therefore, we investigated the
      involvement of LINC01510 in the proliferation of CRC cells. Methods: Microarray
      analysis, In situ hybridization, colony formation assay, MTT assay, Western
      blotting, quantitative RT-PCR and flow cytometry were applied. The two-tailed
      Student's t test and analysis of variance or general linear model of single
      factor variable was used for statistical analyse. Results: In the present study,
      we found that LINC01510 was significantly upregulated in CRC tissues and cell
      lines. The LINC01510 expression level were associated with the
      clinicopathological grade and stage. Meanwhile, gain- and loss-of-function assays
      demonstrated that LINC01510 overexpression increased CRC cell proliferation, and
      promoted cell cycle progression from the G1 phase to the S phase. Further study
      indicated that LINC01510 was positively correlated with the expression of MET,
      and its effects were most likely at the transcriptional level. Conclusions: Taken
      together, our findings suggested that upregulation of LINC01510 contributes to
      the proliferation of CRC cells, at least in part, through the regulation of MET
      protein. LINC01510 could be a candidate prognostic biomarker and a target for new
      therapies in CRC patients.

PMID- 29581706
TI  - Treatment, outcomes, and demographics in sinonasal sarcoma: a systematic review
      of the literature.
AB  - Background: Sarcomas comprise a diverse group of soft tissue mesenchymal
      malignancies. The sinuses and nasal region are a relatively rare site of
      sarcomas. Methods: Retrospective review of the literature on sinonasal sarcomas
      from 1987-2017. Data were analyzed for demographics, treatment type, stage, and
      histopathologic type. Kaplan-Meier analysis was used to assess and compare
      survival. Results: A total of 198 cases of sinonasal sarcoma were identified and
      analyzed. The median age at diagnosis was 39 years. Overall 5-, 10-, and 20-year
      survival was 61.3%, 58.9%, and 49.1%, respectively, and disease-free 5-, 10-, and
      20-year survival was 53.2%, 49.1%, and 38.3%, respectively. Lymph node metastasis
      was present at diagnosis in 3.0% of cases, and distant metastasis was present in
      3.5% of cases. On univariate analysis T stage, overall stage, treatment type,
      histopathologic subtype, and presence of distant metastasis significantly
      affected survival. On multivariate analysis overall stage alone significantly
      predicted overall survival. Open vs. endoscopic surgery, total radiation dose,
      and presence of neck metastasis did not significantly affect survival. Combined
      modality treatment was associated with higher survival rates than single modality
      therapy. Conclusions: Sinonasal sarcoma is a relatively rare malignancy. Lower T
      and overall stage, lack of distant metastasis, and multimodality therapy were
      associated with improved survival. Certain histopathologic subtypes were
      associated with poorer survival.

PMID- 29581708
TI  - Study of the Influence of Age in 18F-FDG PET Images Using a Data-Driven Approach
      and Its Evaluation in Alzheimer's Disease.
AB  - Objectives: 18F-FDG PET scan is one of the most frequently used neural imaging
      scans. However, the influence of age has proven to be the greatest interfering
      factor for many clinical dementia diagnoses when analyzing 18F-FDG PET images,
      since radiologists encounter difficulties when deciding whether the abnormalities
      in specific regions correlate with normal aging, disease, or both. In the present
      paper, the authors aimed to define specific brain regions and determine an age
      correction mathematical model. Methods: A data-driven approach was used based on
      255 healthy subjects. Results: The inferior frontal gyrus, the left medial part
      and the left medial orbital part of superior frontal gyrus, the right insula, the
      left anterior cingulate, the left median cingulate, and paracingulate gyri, and
      bilateral superior temporal gyri were found to have a strong negative correlation
      with age. For evaluation, an age-correction model was applied to 262 healthy
      subjects and 50 AD subjects selected from the ADNI database, and partial
      correlations between SUVR mean and three clinical results were carried out before
      and after age correction. Conclusion: All correlation coefficients were
      significantly improved after the age correction. The proposed model was effective
      in the age correction of both healthy and AD subjects.

PMID- 29581709
TI  - DCE-MRI Pharmacokinetic-Based Phenotyping of Invasive Ductal Carcinoma: A
      Radiomic Study for Prediction of Histological Outcomes.
AB  - Breast cancer is a disease affecting an increasing number of women worldwide.
      Several efforts have been made in the last years to identify imaging biomarker
      and to develop noninvasive diagnostic tools for breast tumor characterization and
      monitoring, which could help in patients' stratification, outcome prediction, and
      treatment personalization. In particular, radiomic approaches have paved the way
      to the study of the cancer imaging phenotypes. In this work, a group of 49
      patients with diagnosis of invasive ductal carcinoma was studied. The purpose of
      this study was to select radiomic features extracted from a DCE-MRI
      pharmacokinetic protocol, including quantitative maps of ktrans, kep, ve, iAUC,
      and R1 and to construct predictive models for the discrimination of molecular
      receptor status (ER+/ER-, PR+/PR-, and HER2+/HER2-), triple negative (TN)/non
      triple negative (NTN), ki67 levels, and tumor grade. A total of 163 features were
      obtained and, after feature set reduction step, followed by feature selection and
      prediction performance estimations, the predictive model coefficients were
      computed for each classification task. The AUC values obtained were 0.826 +/-
      0.006 for ER+/ER-, 0.875 +/- 0.009 for PR+/PR-, 0.838 +/- 0.006 for HER2+/HER2-,
      0.876 +/- 0.007 for TN/NTN, 0.811 +/- 0.005 for ki67+/ki67-, and 0.895 +/- 0.006
      for lowGrade/highGrade. In conclusion, DCE-MRI pharmacokinetic-based phenotyping
      shows promising for discrimination of the histological outcomes.

PMID- 29581710
TI  - Electrocardiographic measures of repolarization dispersion and their
      relationships with echocardiographic indices of ventricular remodeling and
      premature ventricular beats in hypertension.
AB  - Objective: To examine the relationship between Tpeak- Tend interval (Tpe) and
      Tpe/QT ratio with occurrence of ventricular premature beats (VPBs) and left
      ventricular remodeling in hypertension. Methods: A total of 52 patients with mild
      to moderate essential hypertension were included, undergoing echocardiography and
      24-hours Holter monitoring. Ventricular remodeling was assessed by left
      ventricular mass index (LVMI) using the Devereux formula and diastolic function
      by transmitral E and A wave velocities and E/A ratio. Tpe was measured in the
      precordial leads. The end of the T wave was set by the method of the tangent to
      the steepest descending slope of the T wave. Results: Tpe and Tpe/QT in leads V2
      (r = 0.33, P = 0.01; r = 0.27, P = 0.04 respectively) and V3 (r = 0.40, P =
      0.002; r = 0.40, P = 0.003, respectively) correlated significantly with LVMI. A
      significant inverse relationship was observed between E/A ratio and QT (r = 
      0.33, P = 0.01), Tpe in V3 (r = -0.39, P = 0.003) and Tpe/QT in V3 (r = -0.31, P
      = 0.02). Tpe in V3, V5, mean Tpe and maximum Tpe with cut-off values of 60 ms, 59
      ms, 62 ms and 71 ms, respectively, associated with the occurrence of ventricular
      premature beats. Conclusions: The repolarization parameters Tpe interval and
      Tpe/QT ratio correlate with LVMI and indices of left ventricular diastolic
      function and show better predictive values than traditional parameters such as QT
      interval and QT dispersion. Lead V3 is the best lead for measuring Tpe and
      Tpe/QT. These ECG indices can therefore be used in clinical practice to monitor
      LV remodeling and predict occurrence of VPBs.

PMID- 29581711
TI  - Dual versus single antiplatelet therapy for patients with long-term oral
      anticoagulation undergoing coronary intervention: a systematic review and meta
      analysis.
AB  - Objective: The main aim of this meta-analysis is to compare the efficacy and
      safety of dual versus single antiplatelet therapy for patients taking oral
      anticoagulation (OAC) after coronary intervention. Background: The optimal
      regimen remains controversial for patients taking OAC after coronary
      intervention. Methods: PubMed, Embase and Cochrane Central Register of Controlled
      Trials were searched for eligible studies including data of triple therapy (TT)
      versus OAC plus single antiplatelet therapy for patients requiring OAC after
      coronary intervention. The primary outcome was major adverse cardiac and
      cerebrovascular event (MACCE). The safety outcome was major bleeding. Results:
      Fourteen studies with 32,825 patients were included. Among prospective studies,
      patients with TT had a trend toward a higher risk of major bleeding [odds ratios
      (OR): 1.56, 95% confidence interval (CI): 0.98-2.49, P = 0.06] and a markedly
      higher risk of all-cause death (OR; 2.11, 95% CI: 1.10-4.06 P = 0.02) compared
      with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of
      MACCE (OR: 0.63, 95% CI: 051-0.77 P < 0.0001), all-cause death (OR: 0.45, 95% CI:
      0.20-0.97, P = 0.04), and stroke/transient ischemic attack (TIA)/peripheral
      embolism (PE) (OR: 0.29, 95% CI: 0.09-0.96, P = 0.04) compared with OAC plus
      aspirin. Conclusions: For patients requiring OAC after coronary intervention, OAC
      plus clopidogrel may bring more clinical net benefit than TT, whereas OAC plus
      aspirin should be the last choice. More large-size randomized control trials are
      needed to confirm these findings.

PMID- 29581712
TI  - Predictors of super-response to cardiac resynchronization therapy: the
      significance of heart failure medication, pre-implant left ventricular geometry
      and high percentage of biventricular pacing.
AB  - Background: Super-responders (SRs) are defined as patients who show crucial
      cardiac function improvement after cardiac resynchronization therapy (CRT). The
      purpose of this study is to identify and validate predictors of SRs after CRT.
      Methods: This study enrolled 201 patients who underwent CRT during the period
      from 2010 to 2014. Clinical and echocardiographic evaluations were conducted
      before CRT and 6 months after. Patients with a decrease in New York Heart
      Association (NYHA) functional class >= 1, a decrease in left ventricular end
      systolic volume (LVESV) >= 15%, and a final left ventricular ejection fraction
      (LVEF) >= 45% were classified as SRs. Results: 29% of the 201 patients who
      underwent CRT were identified as SRs. At baseline, SRs had significantly smaller
      left atrial diameter (LAD), LVESV, left ventricular end-diastolic volume (LVEDV)
      and higher LVEF than the non-super-responders (non-SRs). The percentage of
      patients using angiotensin-converting enzyme inhibitors or angiotensin receptor
      blockers (ACEI/ARB) was higher in SRs than non-SRs. Most SRs had Biventricular
      (BiV) pacing percentage greater than 98% six months after CRT. In the
      multivariate logistic regression analysis, the independent predictors of SRs were
      lower LVEDV [odd ratios (OR): 0.93; confidence intervals (CI): 0.90-0.97], use of
      ACEI/ARB (OR: 0.33; CI: 0.13-0.82) and BiV pacing percentage greater than 98%
      (OR: 0.29; CI: 0.16-0.87). Conclusion: Patients with a better compliance of
      ACEI/ARB and a less ectatic ventricular geometry before CRT tends to have a
      greater probability of becoming SRs. Higher percentage of BiV pacing is essential
      for becoming SRs.

PMID- 29581713
TI  - Effect of advanced age on plasma homocysteine levels and its association with
      ischemic stroke in non-valvular atrial fibrillation.
AB  - Background: Elevated homocysteine (Hcy) has been reported to be associated with
      cardiovascular events in atrial fibrillation (AF) patients, while the age-related
      expression pattern of plasma Hcy in AF remains unknown. The study was aimed to
      investigate the effect of advanced age on plasma Hcy levels and its association
      with ischemic stroke in non-valvular AF patients. Methods: A total of 2562
      consecutive patients with non-valvular AF and 535 controls were enrolled and
      divided into six age groups. Plasma Hcy levels were analyzed among different age
      groups, and the effect of advanced age on Hcy was investigated. Results: Plasma
      Hcy levels did not show any difference among groups aged below 65 years, while it
      increased sharply in patients aged 65-74 years and aged over 75 years (15.7 +/-
      4.6 umol/L, 17.1 +/- 4.9 umol/L, both P < 0.01 compared with the first four age
      groups). Hcy was much higher in AF patients than in controls at the same age
      group (all P < 0.05). The proportion of patients with hyperhomocysteinemia
      increased gradually with age from 32.3%, 29.2%, 31.2%, 32.4%, 45.9%, to 51.4% in
      six age groups. The concentration of Hcy in AF patients with ischemic stroke
      increased progressively with age, and was higher than those without stroke at the
      same age. Logistic regression analysis demonstrated that age 65-74 years [odds
      ratios (OR): 1.742, 95% confidence interval (CI): 1.223-2.482, P = 0.002] and age
      >= 75 years (OR: 2.637, 95% CI: 1.605-4.335, P < 0.001) were significantly
      independent predictors of elevated plasma Hcy levels. Conclusions: Advanced age
      was significantly associated with elevated Hcy levels, which may provide a
      possible explanation for the progressive increase in ischemic stroke especially
      in elderly AF patients.

PMID- 29581715
TI  - Transcatheter Valve-in-Valve implantation after late migration of balloon
      expandable Sapien-XT prosthesis in a severe pure aortic regurgitation case.

PMID- 29581714
TI  - Congenital left ventricular aneurysms and diverticula: an entity in search of an
      identity.
AB  - Congenital left ventricular aneurysm or diverticulum are rare cardiac
      malformations described in 809 cases since the first description in 1816, being
      associated with other cardiac, vascular or thoraco-abdominal abnormalities in
      about 70%. It appears to be a developmental anomaly, starting in the 4th
      embryonic week. In an experimental study, targeted knockdown of cardiac troponin
      T in the chick was performed at day 3, after the heart tube has formed.
      Morpholino treatment of gene TNNT2 at this stage led to the development of left
      ventricular diverticula (LVD) in the primitive left ventricular wall. Diagnosis
      of left ventricular aneurysms (LVA)/LVD can be made after exclusion of coronary
      artery disease, local or systemic inflammation or traumatic causes as well as
      cardiomyopathies. Clinically, most of LVA and LVD are asymptomatic or may cause
      systemic embolization, congestive heart failure, valvular regurgitation,
      ventricular wall rupture, ventricular tachycardia or sudden cardiac death.
      Diagnosis is established by imaging studies (echocardiography, magnetic resonance
      imaging or left ventricular angiography) visualizing the structural changes and
      accompanying abnormalities. Mode of treatment has to be individually tailored and
      depends on clinical presentation, accompanying abnormalities and possible
      complications, options include surgical resection (especially in symptomatic
      patients), anticoagulation after systemic embolization, radiofrequency ablation
      or implantation of an implantable cardioverter defibrillator (ICD) in case of
      symptomatic ventricular tachycardias, and occasionally combined with class I- or
      III-antiarrhythmic drugs. Cardiac death occurs usually in childhood, is
      significantly more frequent in LVA patients and caused by congestive heart
      failure in most of the cases, whereas patients diagnosed with LVD died more
      frequently from rupture of the LVD.

PMID- 29581716
TI  - A meta-analysis of soluble suppression of tumorigenicity 2 (sST2) and clinical
      outcomes in pulmonary hypertension.

PMID- 29581717
TI  - Spontaneous diffuse vasospasm simultaneously found at left main trunk, left
      anterior descending, left circumflex and right coronary arteries.

PMID- 29581718
TI  - Meta-analysis of T-wave indices for risk stratification in myocardial infarction.

PMID- 29581719
TI  - The relationship between neutrophil-to-lymphocyte ratio and major cardiovascular
      events in elderly patients with chronic heart failure.

PMID- 29581720
TI  - Adsorption Characteristics of Bixin on Acid- and Alkali-Treated Kaolinite in
      Aprotic Solvents.
AB  - The adsorption of bixin in aprotic solvents onto acid- and alkali-treated
      kaolinite was investigated. Kaolinite was treated three times, for 6 h each, with
      8 M HCl or 5 M KOH. The adsorbents were characterized by XRD, FT-IR, EDS, and BET
      N2. The effects of contact time and dye concentration on adsorption capacity and
      kinetics, electronic transition of bixin before and after adsorption, and also
      mechanism of bixin-kaolinite adsorption were investigated. Dye adsorption
      followed pseudo-second order kinetics and was faster in acetone than in dimethyl
      carbonate. The best adsorption results were obtained for KOH-treated kaolinite.
      In both of the solvents, the adsorption isotherm followed the Langmuir model and
      adsorption capacity was higher in dimethyl carbonate (qm  = 0.43 mg/g) than in
      acetone (0.29 mg/g). The adsorption capacity and kinetics of KOH-treated
      kaolinite (qm  = 0.43 mg/g, k2 = 3.27 g/mg.min) were better than those of HCl
      treated kaolinite (qm  = 0.21 mg/g, k2 = 0.25 g/mg.min) and natural kaolinite (qm
      = 0.18 mg/g, k2 = 0.32 g/mg.min). There are shift in the band position of
      maximum intensity of bixin after adsorption on this adsorbent. Adsorption in this
      system seemed to be based essentially on chemisorption due to the electrostatic
      interaction of bixin with the strong basic and reducing sites of kaolinite.

PMID- 29581721
TI  - Feature Selection for Object-Based Classification of High-Resolution Remote
      Sensing Images Based on the Combination of a Genetic Algorithm and Tabu Search.
AB  - In object-based image analysis of high-resolution images, the number of features
      can reach hundreds, so it is necessary to perform feature reduction prior to
      classification. In this paper, a feature selection method based on the
      combination of a genetic algorithm (GA) and tabu search (TS) is presented. The
      proposed GATS method aims to reduce the premature convergence of the GA by the
      use of TS. A prematurity index is first defined to judge the convergence
      situation during the search. When premature convergence does take place, an
      improved mutation operator is executed, in which TS is performed on individuals
      with higher fitness values. As for the other individuals with lower fitness
      values, mutation with a higher probability is carried out. Experiments using the
      proposed GATS feature selection method and three other methods, a standard GA,
      the multistart TS method, and ReliefF, were conducted on WorldView-2 and
      QuickBird images. The experimental results showed that the proposed method
      outperforms the other methods in terms of the final classification accuracy.

PMID- 29581722
TI  - A Two-Stream Deep Fusion Framework for High-Resolution Aerial Scene
      Classification.
AB  - One of the challenging problems in understanding high-resolution remote sensing
      images is aerial scene classification. A well-designed feature representation
      method and classifier can improve classification accuracy. In this paper, we
      construct a new two-stream deep architecture for aerial scene classification.
      First, we use two pretrained convolutional neural networks (CNNs) as feature
      extractor to learn deep features from the original aerial image and the processed
      aerial image through saliency detection, respectively. Second, two feature fusion
      strategies are adopted to fuse the two different types of deep convolutional
      features extracted by the original RGB stream and the saliency stream. Finally,
      we use the extreme learning machine (ELM) classifier for final classification
      with the fused features. The effectiveness of the proposed architecture is tested
      on four challenging datasets: UC-Merced dataset with 21 scene categories, WHU-RS
      dataset with 19 scene categories, AID dataset with 30 scene categories, and NWPU
      RESISC45 dataset with 45 challenging scene categories. The experimental results
      demonstrate that our architecture gets a significant classification accuracy
      improvement over all state-of-the-art references.

PMID- 29581723
TI  - Optimum Extraction, Characterization, and Antioxidant Activities of
      Polysaccharides from Flowers of Dendrobium devonianum.
AB  - Response surface methodology (RSM) was employed to optimize the conditions for
      the ultrasonic-assisted extraction (UAE) of polysaccharides from the flowers of
      Dendrobium devonianum. The optimal conditions for the maximum yields of DDFPs are
      as follows: an extraction temperature of 63.13 degrees C, an extraction time of
      53.10 min, and a water-to-raw material ratio of 22.11 mL/g. Furthermore, three
      fractions (DDFPs30, DDFPs50, and DDFPs70) were prepared from Dendrobium
      devonianum flowers polysaccharides (DDFPs) by the stepwise ethanol precipitation
      method. The DDFPs50 exhibited the highest antioxidant activity compared to the
      other fractions. The molecular weight, polydispersity, and conformation of these
      fractions were also characterized. In particular, the monosaccharide composition
      analysis of the DDFPs indicates that mannose and glucose are the primary
      components, similar to those of the D. officinale plant. This study provides a
      rapid extraction technology and essential information for the production of
      DDFPs, which could be potentially used as healthcare food.

PMID- 29581725
TI  - Comparison of the Screening Tests for Gestational Diabetes Mellitus between "One
      Step" and "Two-Step" Methods among Thai Pregnant Women.
AB  - Objective: To compare the prevalence and pregnancy outcomes of GDM between those
      screened by the "one-step" (75 gm GTT) and "two-step" (100 gm GTT) methods.
      Methods: A prospective study was conducted on singleton pregnancies at low or
      average risk of GDM. All were screened between 24 and 28 weeks, using the one
      step or two-step method based on patients' preference. The primary outcome was
      prevalence of GDM, and secondary outcomes included birthweight, gestational age,
      rates of preterm birth, small/large-for-gestational age, low Apgar scores,
      cesarean section, and pregnancy-induced hypertension. Results: A total of 648
      women were screened: 278 in the one-step group and 370 in the two-step group. The
      prevalence of GDM was significantly higher in the one-step group; 32.0% versus
      10.3%. Baseline characteristics and pregnancy outcomes in both groups were
      comparable. However, mean birthweight was significantly higher among pregnancies
      with GDM diagnosed by the two-step approach (3204 +/- 555 versus 3009 +/- 666 g;
      p=0.022). Likewise, the rate of large-for-date tended to be higher in the two
      step group, but was not significant. Conclusion: The one-step approach is
      associated with very high prevalence of GDM among Thai population, without clear
      evidence of better outcomes. Thus, this approach may not be appropriate for
      screening in a busy antenatal care clinic like our setting or other centers in
      developing countries.

PMID- 29581724
TI  - Behaviour of the Foramen Ovale Flow in Fetuses with Intrauterine Growth
      Restriction.
AB  - Background: Foramen ovale (FO) flow may be altered in IUGR. This study was
      designed to test this hypothesis. Methods: Forty pregnant women (24-38 weeks)
      were divided into 3 groups: group I (IUGR), group II (adequate growth and
      maternal hypertension), and group III (normal controls). Impedance across the FO
      was assessed by the FO pulsatility index (FOPI): (systolic velocity - presystolic
      velocity)/mean velocity. Statistical analysis utilized ANOVA, Tukey test, and ROC
      curves. Results: Mean FOPI in IUGR fetuses (n = 15) was 3.70 +/- 0.99 (3.15
      4.26); in the group II (n = 12), it was 2.84 +/- 0.69 (2.40-3.28), and in the
      group III (n = 13), it was 2.77 +/- 0.44 (2.50-3.04) (p=0.004). FOPI and UtA RI
      were correlated (r = 0.375, p=0.017), as well as FOPI and UA RI (r = 0.356,
      p=0.024) and, inversely, FOPI and MCA RI (r = -0.359, p=0.023). Conclusions: The
      FO flow pulsatility index is increased in fetuses with IUGR, probably as a result
      of impaired left ventricular diastolic function.

PMID- 29581726
TI  - Estimation of leaf traits from reflectance measurements: comparison between
      methods based on vegetation indices and several versions of the PROSPECT model.
AB  - Background: Leaf biochemical composition corresponds to traits related to the
      plant state and its functioning. This study puts the emphasis on the main leaf
      absorbers: chlorophyll a and b ([Formula: see text]), carotenoids ([Formula: see
      text]), water ([Formula: see text]) and dry mater ([Formula: see text]) contents.
      Two main approaches were used to estimate [[Formula: see text] [Formula: see
      text], [Formula: see text], [Formula: see text]] in a non-destructive way using
      spectral measurements. The first one consists in building empirical relationships
      from experimental datasets using either the raw reflectances or their combination
      into vegetation indices (VI). The second one relies on the inversion of
      physically based models of leaf optical properties. Although the first approach
      is commonly used, the calibration of the empirical relationships is generally
      conducted over a limited dataset. Consequently, poor predictions may be observed
      when applying them on cases that are not represented in the training dataset,
      i.e. when dealing with different species, genotypes or under contrasted
      environmental conditions. The retrieval performances of the selected VIs were
      thus compared to the ones of four PROSPECT model versions based on reflectance
      data acquired at two phenological stages, over six wheat genotypes grown under
      three different nitrogen fertilizations and two sowing density modalities. Leaf
      reflectance was measured in the lab with a spectrophotometer equipped with an
      integrating sphere, the leaf being placed in front of a white Teflon background
      to increase the sensitivity to leaf biochemical composition. Destructive
      measurements of [[Formula: see text] [Formula: see text], [Formula: see text],
      [Formula: see text]] were performed concurrently. Results: The destructive
      measurements demonstrated that the carotenoid, [Formula: see text], and
      chlorophyll, [Formula: see text], contents were strongly correlated (r2 = 0.91).
      The sum of [Formula: see text] and [Formula: see text], i.e. the total
      chlorophyllian pigment content, [Formula: see text], was therefore used in this
      study. When inverting the PROSPECT model, accounting for the brown pigment
      content, [Formula: see text], was necessary when leaves started to senesce. The
      values of [Formula: see text] and [Formula: see text] were well estimated (r2 =
      0.81 and r2 = 0.88 respectively) while the dry matter content, [Formula: see
      text], was poorly estimated (r2 = 0.00). Retrieval of [Formula: see text] from
      PROSPECT versions was only slightly biased, while substantial overestimation of
      [Formula: see text] was observed. The ranking between estimated values of
      [Formula: see text] and [Formula: see text] from the several PROSPECT versions
      and that derived using the VIs were similar to the ranking observed over the
      destructively measured values of [Formula: see text] and [Formula: see text].
      Conclusions: PROSPECT model inversion and empirical VI approach provide similar
      retrieval performances and are useful methods to estimate leaf biochemical
      composition from spectral measurements. However, the PROSPECT model inversion
      gives potential access to additional traits on surface reflectivity and leaf
      internal structure. This study suggests that non-destructive estimation of leaf
      chlorophyll and water contents is a relevant method to provide leaf traits with
      relatively high throughput.

PMID- 29581727
TI  - Reference gene identification for reliable normalisation of quantitative RT-PCR
      data in Setaria viridis.
AB  - Background: Quantitative real-time polymerase chain reaction (RT-qPCR) is the key
      platform for the quantitative analysis of gene expression in a wide range of
      experimental systems and conditions. However, the accuracy and reproducibility of
      gene expression quantification via RT-qPCR is entirely dependent on the
      identification of reliable reference genes for data normalisation. Green foxtail
      (Setaria viridis) has recently been proposed as a potential experimental model
      for the study of C4 photosynthesis and is closely related to many economically
      important crop species of the Panicoideae subfamily of grasses, including Zea
      mays (maize), Sorghum bicolor (sorghum) and Sacchurum officinarum (sugarcane).
      Setaria viridis (Accession 10) possesses a number of key traits as an
      experimental model, namely; (i) a small sized, sequenced and well annotated
      genome; (ii) short stature and generation time; (iii) prolific seed production,
      and; (iv) is amendable to Agrobacterium tumefaciens-mediated transformation.
      There is currently however, a lack of reference gene expression information for
      Setaria viridis (S. viridis). We therefore aimed to identify a cohort of suitable
      S. viridis reference genes for accurate and reliable normalisation of S. viridis
      RT-qPCR expression data. Results: Eleven putative candidate reference genes were
      identified and examined across thirteen different S. viridis tissues. Of these,
      the geNorm and NormFinder analysis software identified SERINE/THERONINE-PROTEIN
      PHOSPHATASE 2A (PP2A), 5'-ADENYLYLSULFATE REDUCTASE 6 (ASPR6) and DUAL
      SPECIFICITY PHOSPHATASE (DUSP) as the most suitable combination of reference
      genes for the accurate and reliable normalisation of S. viridis RT-qPCR
      expression data. To demonstrate the suitability of the three selected reference
      genes, PP2A, ASPR6 and DUSP, were used to normalise the expression of CINNAMYL
      ALCOHOL DEHYDROGENASE (CAD) genes across the same tissues. Conclusions: This
      approach readily demonstrated the suitably of the three selected reference genes
      for the accurate and reliable normalisation of S. viridis RT-qPCR expression
      data. Further, the work reported here forms a highly useful platform for future
      gene expression quantification in S. viridis and can also be potentially directly
      translatable to other closely related and agronomically important C4 crop
      species.

PMID- 29581728
TI  - Design of a Conceptual Bumper Energy Absorber Coupling Pedestrian Safety and Low
      Speed Impact Requirements.
AB  - The car front bumper system needs to meet the requirements of both pedestrian
      safety and low-speed impact which are somewhat contradicting. This study aims to
      design a new kind of modular self-adaptive energy absorber of the front bumper
      system which can balance the two performances. The X-shaped energy-absorbing
      structure was proposed which can enhance the energy absorption capacity during
      impact by changing its deformation mode based on the amount of external collision
      energy. Then, finite element simulations with a realistic vehicle bumper system
      are performed to demonstrate its crashworthiness in comparison with the
      traditional foam energy absorber, which presents a significant improvement of the
      two performances. Furthermore, the structural parameters of the X-shaped energy
      absorbing structure including thickness (tu), side arc radius (R), and clamping
      boost beam thickness (tb) are analyzed using a full factorial method, and a
      multiobjective optimization is implemented regarding evaluation indexes of both
      pedestrian safety and low-speed impact. The optimal parameters are then verified,
      and the feasibility of the optimal results is confirmed. In conclusion, the new X
      shaped energy absorber can meet both pedestrian safety and low-speed impact
      requirements well by altering the main deformation modes according to different
      impact energy levels.

PMID- 29581729
TI  - National profile of foot orthotic provision in the United Kingdom, part 2:
      podiatrist, orthotist and physiotherapy practices.
AB  - Background: A national survey recently provided the first description of foot
      orthotic provision in the United Kingdom. This article aims to profile and
      compare the foot orthoses practice of podiatrists, orthotists and
      physiotherapists within the current provision. Method: Quantitative data were
      collected from podiatrists, orthotists and physiotherapists via an online
      questionnaire. The topics, questions and answers were developed through a series
      of pilot phases. The professions were targeted through electronic and printed
      materials advertising the survey. Data were captured over a 10 month period in
      2016. Differences between professions were investigated using Chi squared and
      Fischer's exact tests, and regression analysis was used to predict the likelihood
      of each aspect of practice in each of the three professions. Results: Responses
      from 357 podiatrists, 93 orthotists and 49 physiotherapists were included in the
      analysis. The results reveal statistically significant differences in employment
      and clinical arrangements, the clinical populations treated, and the nature and
      volume of foot orthoses caseload. Conclusion: Podiatrists, orthotists and
      physiotherapists provide foot orthoses to important clinical populations in both
      a prevention and treatment capacity. Their working context, scope of practice and
      mix of clinical caseload differs significantly, although there are areas of
      overlap. Addressing variations in practice could align this collective workforce
      to national allied health policy.

PMID- 29581730
TI  - The impact of Rhodiola rosea on the gut microbial community of Drosophila
      melanogaster.
AB  - Background: The root extract of Rhodiola rosea has historically been used in
      Europe and Asia as an adaptogen, and similar to ginseng and Shisandra, shown to
      display numerous health benefits in humans, such as decreasing fatigue and
      anxiety while improving mood, memory, and stamina. A similar extract in the
      Rhodiola family, Rhodiola crenulata, has previously been shown to confer positive
      effects on the gut homeostasis of the fruit fly, Drosophila melanogaster.
      Although, R. rosea has been shown to extend lifespan of many organisms such as
      fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using
      D. melanogaster as our model system, the purpose of this work was to examine
      whether the anti-aging properties of R. rosea are due to its impact on the
      microbial composition of the fly gut. Results: Rhodiola rosea treatment
      significantly increased the abundance of Acetobacter, while subsequently
      decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of
      age. Additionally, supplementation of the extract decreased the total culturable
      bacterial load of the fly gut, while increasing the overall quantifiable
      bacterial load. The extract did not display any antimicrobial activity when disk
      diffusion tests were performed on bacteria belonging to Microbacterium, Bacillus,
      and Lactococcus. Conclusions: Under standard and conventional rearing conditions,
      supplementation of R. rosea significantly alters the microbial community of the
      fly gut, but without any general antibacterial activity. Further studies should
      investigate whether R. rosea impacts the gut immunity across multiple animal
      models and ages.

PMID- 29581731
TI  - MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by
      targeting silent information regulator 1.
AB  - The present study aimed to identify whether microRNA (miRNA/miR)-34a regulates
      the proliferation and apoptosis of gastric cancer cells by targeting silent
      information regulator 1 (SIRT1). The expression of miR-34a and SIRT1 and cell
      viability was investigated in gastric cancer cells. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) was applied to determine miR-34a
      expression in gastric adenocarcinoma, normal pericarcinomatous tissues, human
      normal gastric mucosa epithelial cell line GES and various gastric cancer cell
      strains. A bioinformatics method was then used to predict the target gene of miR
      34a. A human miR-34a over expression lentiviral vector system was constructed and
      then used for transfection of the gastric cancer cell line SCG-7901 to determine
      the expression of SIRT1 mRNA and SIRT1 protein using RT-qPCR and western blot
      analysis. The MTT method and flow cytometry was used to measure cell
      proliferation and apoptosis. The relative expression of miR-34a in gastric cancer
      tissues was significantly decreased compared with that in normal tissues
      (P<0.01). miR-34a expression was also significantly decreased in low
      differentiated N2, N3 gastric cancer tissues (P<0.01). However, tumor size and
      filtration degree were not significantly associated with miR-34a expression. The
      relative expression of miR-34a was decreased in gastric cancer cells, especially
      in the SGC-7901 cell line (P<0.01) compared with the GES group. The relative
      expression of SIRT1 protein was decreased in the miR-34a group compared with the
      negative control (P<0.01). The rate of proliferation was significantly decreased,
      whereas the rate of apoptosis was significantly increased in the miR-34a group
      compared with the NC group (P<0.01). Therefore, the present results suggested
      that miRNA-34a serves a pivotal role in gastric cancer as a cancer suppressor
      gene by targeting SIRT1 to regulate the proliferation and apoptosis of gastric
      cancer cells.

PMID- 29581733
TI  - Decreased expression of sirtuin 3 protein correlates with early stage chronic
      renal allograft dysfunction in a rat kidney model.
AB  - Chronic renal allograft dysfunction (CRAD) is the primary factor affecting the
      long-term survival of patients who have undergone renal transplantation.
      Oxidative stress and inflammation serve an important role in the pathological
      damage caused by CRAD in the early post-transplantation phase. Previous studies
      have demonstrated that sirtuin 3 (sirt3) protects cells from oxidative stress and
      inflammation. A model of renal orthotopic transplantation was established in the
      current study and kidney samples were harvested from the rats 12 weeks following
      surgery. Compared with the control groups, there were significantly increased
      levels of serum creatinine, blood urea nitrogen and 24 h urinary protein in the
      allograft group (P<0.05). Pathological examinations indicated mononuclear cell
      infiltration and intimal proliferation in the allograft group, which had a higher
      Banff score compared with the control groups. There were increased levels of
      malondialdehyde, decreased sirt3 protein expression and decreased superoxide
      dismutase enzyme activity in the allograft group compared with the control groups
      (P<0.05). In addition, there was a negative correlation between the expression of
      sirt3 and 24 h urinary protein excretion, serum creatinine levels,
      tubulointerstitial mononuclear cell infiltration, smooth muscle cell migration in
      the vascular wall and Banff scores. Thus, sirt3 may serve an important protective
      role in the early stage of CRAD.

PMID- 29581732
TI  - Isolation, culture and induced differentiation of rabbit mesenchymal stem cells
      into osteoblasts.
AB  - Mesenchymal stem cells (MSCs) may be easily isolated from the bone marrow, and
      possess multi-lineage differentiation potential and various therapeutic
      applications. The differentiation of MSCs into osteoblasts is a complex process
      that is regulated by multiple internal and external factors. In the present
      study, the differentiation of MSCs isolated from rabbit bone marrow into
      osteoblasts using different osteoblast inductive media in the presence of
      dexamethasone, bone morphogenetic protein 2 (BMP-2), 1,25-dihydroxyvitamin D3,
      transforming growth factor beta (TGFbeta), platelet lysate and cyclooxygenase 2
      (COX2), respectively. Alkaline phosphatase (ALP) activity, mineralization,
      collagen type (Ct) I and osteocalcin activities, and the mRNA and protein
      expression levels of vascular endothelial growth factor (VEGF), BMP-2 and Ct II
      were measured during the differentiation process in MSCs treated with different
      inducers. Rabbit MSCs were successfully isolated and were observed to be
      predominantly circular in shape after culture for 24 h. Following subculture for
      5 days, the cells demonstrated a spindle shape. ALP, Ct I and osteocalcin
      activities were higher in cells cultured in dexamethasone, BMP-2 and TGFbeta
      compared with the activities in control cells. Following differentiation, the
      dexamethasone, BMP-2 and TGFbeta groups demonstrated significantly enhanced
      mineralization of MSCs detected by Alizarin Red S staining. The mRNA and protein
      expression levels of VEGF, BMP-2 and Ct II were significantly increased in the
      same groups compared with the levels in the control group. In conclusion, rabbit
      MSCs were successfully isolated from bone marrow and differentiated into
      osteoblasts indicated by raised ALP, Ct I and osteocalcin activities,
      mineralization and expression of osteogenesis-inducing genes and proteins. The
      present study revealed that dexamethasone, BMP-2 and TGFbeta have a positive
      effect on cell differentiation.

PMID- 29581734
TI  - MicroRNA-133b inhibits cell proliferation and promotes apoptosis by targeting
      cullin 4B in esophageal squamous cell carcinoma.
AB  - microRNAs (miRs) serve a role as modulators during carcinogenesis. It has been
      demonstrated that the expression of miR-133b is decreased in a variety of tumor
      tissues and cell lines and serves a suppressive role in the proliferation and
      apoptosis of different types of tumor cells. However, its effect on esophageal
      squamous cell carcinoma (ESCC) cells remains unclear. In the current study, the
      expression of mature miR-133b was measured using reverse transcription
      quantitative polymerase chain reaction and the results indicated that miR-133b
      was significantly downregulated in ESCC tissues and various ESCC cell lines. The
      overexpression of miR-133b significantly inhibited the proliferation and promoted
      the apoptosis of KYSE150 and Eca-109 cells. Furthermore, it was demonstrated that
      cullin 4B (CUL4B) promotes ESCC cell proliferation and inhibits apoptosis by
      activating the protein kinase B/glycogen synthase kinase 3beta/beta-catenin
      pathway. Taken together, these results demonstrate that miR-133b/CUL4B serves a
      tumor suppressive role during ESCC progression and may therefore be used as a
      potential target to treat patients with ESCC.

PMID- 29581735
TI  - Reverting doxorubicin resistance in colon cancer by targeting a key signaling
      protein, steroid receptor coactivator.
AB  - Although there have been notable improvements in treatments against cancer,
      further research is required. In colon cancer, nearly all patients eventually
      experience drug resistance and stop responding to the approved drugs, making
      treatment difficult. Steroid receptor coactivator (SRC) is an oncogenic nuclear
      receptor coactivator that serves an important role in drug resistance. The
      present study generated a doxorubicin-resistant colon cancer cell line, in which
      the upregulation/activation of SRC was responsible for drug resistance, which in
      turn activated AKT. Overexpression of receptor tyrosine kinase-like epidermal
      growth factor receptor and insulin-like growth factor 1 receptor also induced SRC
      expression. It was observed that doxorubicin resistance in colon cancer also
      induced epithelial to mesenchymal transition, a decrease in expression of
      epithelial marker E-cadherin and an increase in the expression of mesenchymal
      markers, including N-cadherin and vimentin. Additionally, the present study
      indicated that SRC acts as a common signaling node, and inhibiting SRC in
      combination with doxorubicin treatment in doxorubicin-resistant cells aids in
      reversing the resistance. Thus, the present study suggests that activation of SRC
      is responsible for doxorubicin resistance in colon cancer. However, further
      research is required to understand the complete mechanism of how drug resistance
      occurs and how it may be tackled to treat patients.

PMID- 29581736
TI  - miR-143-3p regulates cell proliferation and apoptosis by targeting IGF1R and
      IGFBP5 and regulating the Ras/p38 MAPK signaling pathway in rheumatoid arthritis.
AB  - It has been demonstrated that the deregulation of microRNAs (miRNAs) affects the
      development of rheumatoid arthritis (RA). The primary objective of the current
      study was to determine the role of miR-143-3p in the progression of RA. The
      expression of miR-143-3p in synovium taken from patients with RA was assessed by
      reverse transcription-quantitative polymerase chain reaction. The expression of
      miR-143-3p was higher in synovium tissues of RA than that of osteoarthritis (OA).
      The decreased expression of miR-143-3p suppressed cell proliferation and promoted
      apoptosis in vitro. In addition, inhibition of miR-143-3p decreased levels of
      inflammatory cytokines, as determined by an enzyme-linked immunosorbent assay.
      IGF1R and IGFBP5 were found to be the target genes of miR-143-3p, and it was
      demonstrated that miR-143-3p regulated the proliferation and apoptosis of MH7A
      cells by targeting IGF1R and IGFBP5. Furthermore, TNF-alpha treatment stimulated
      the Ras/p38 mitogen activated protein kinase (MAPK) signaling pathway, whereas
      miR-143-3p inhibition suppressed it. The results of the current study indicate
      that miR-143-3p may regulate cell proliferation and apoptosis by targeting IGF1R
      and IGFBP5 expression and regulating the Ras/p38 MAPK signaling pathways.
      Therefore, miR-143-3p may be a novel therapeutic target in RA.

PMID- 29581737
TI  - Chronic ethanol exposure induces SK-N-SH cell apoptosis by increasing N-methyl-D
      aspartic acid receptor expression and intracellular calcium.
AB  - It has been identified that chronic ethanol exposure damages the nervous system,
      particularly neurons. There is scientific evidence suggesting that neuronal loss
      caused by chronic ethanol exposure has an association with neuron apoptosis and
      intracellular calcium oscillation is one of the primary inducers of apoptosis.
      Therefore, the present study aimed to investigate the inductive effects of
      intracellular calcium oscillation on apoptosis in SK-N-SH human neuroblastoma
      cells and the protective effects of the N-methyl-D-aspartic acid receptor (NMDAR)
      antagonist, memantine, on SK-N-SH cell apoptosis caused by chronic ethanol
      exposure. SK-N-SH cells were treated with 100 mM ethanol and memantine (4 uM) for
      2 days. Protein expression of NR1 was downregulated by RNA interference (RNAi).
      Apoptosis was detected by Annexin V/propidium iodide (PI) double-staining and
      flow cytometry and cell viability was detected using an MTS kit. Fluorescence
      dual wavelength spectrophotometry was used to determine the intracellular calcium
      concentration and the levels of NR1 and caspase-3 were detected using western
      blotting. NR1 mRNA levels were also detected using qPCR. It was found that
      chronic ethanol exposure reduced neuronal cell viability and caused apoptosis of
      SK-N-SH cells, and the extent of damage in SK-N-SH cells was associated with
      ethanol exposure concentration and time. In addition, chronic ethanol exposure
      increased the concentration of intracellular calcium in SK-N-SH cells by inducing
      the expression of NMDAR, resulting in apoptosis, and memantine treatment reduced
      ethanol-induced cell apoptosis. The results of the present study indicate that
      the application of memantine may provide a novel strategy for the treatment of
      alcoholic dementia.

PMID- 29581738
TI  - Effect of probucol on hemodynamics, rheology and blood lipid of diabetic
      retinopathy.
AB  - The effect of probucol in the treatment of diabetic retinopathy was investigated
      to analyze its impact on its hemodynamics, rheology and blood lipid. A total of
      80 patients with diabetic retinopathy who were treated in the Ninth People's
      Hospital of Chongqing (Chongqing, China) from January 2015 to August 2016 were
      selected and divided into two groups by random number table, with 40 patients in
      each group. Control group was treated by conventional and intensive glycemic
      control and antihypertensive therapy, while observation group was orally
      administered with 0.375 g probucol twice a day on the basis of intensive therapy.
      Outpatient follow-up was performed to all the patients for 6 months, then, among
      the blood rheology, the changes in blood viscosity and erythrocyte aggregation
      indexes at different time points before and after intervention in the two groups
      were compared, mean blood flow velocities in renal artery, renal artery pulse
      indexes and renal artery resistance indexes at different time points were
      recorded, changes in blood lipid of the two groups before and after intervention
      were compared, and complication rates during the treatment were calculated. After
      intervention, the whole blood viscosity at high shear rate, whole blood viscosity
      at low shear rate and plasma viscosity in observation group were lower than those
      before intervention and lower than those in control group after intervention
      (P<0.05); The erythrocyte aggregation indexes in observation group were obviously
      increased compared with those in control group at 1 week, 1 month and 6 months
      after intervention (P<0.05). The mean blood flow velocities in renal artery in
      observation group were remarkably higher than those in control group at 1 week, 1
      month and 6 months after intervention (P<0.05), while the renal artery pulse
      indexes and resistance indexes in observation group were lower than those in
      control group in the same period (P<0.05). In observation group, the levels of
      total cholesterol (TC), triglyeride (TG) and low density lipoprotein cholesterol
      (LDL-C) after intervention were decreased compared with those before
      intervention, while the level of high-density lipoprotein cholesterol (HDL-C) was
      increased. The levels of TC, TG and LDL-C in observation group were lower than
      those in control group after intervention, while the HDL-C level was higher
      (P<0.05). During the treatment, the total incidence of phlebitis, chills, fever,
      rash and maculopapule in observation group was obviously lower than that in
      control group. Probucol can significantly improve the hemodynamic and rheological
      indexes and lower blood lipid in the body, and is an effective medicine for
      diabetic retinopathy.

PMID- 29581739
TI  - Investigating the application of diving endoscopic technique in determining the
      extent of pituitary adenoma resection via the trans-nasal-sphenoidal approach.
AB  - The aim of the present study was to investigate the advantages and disadvantages
      of the diving endoscopic technique in pituitary adenoma surgery, and the
      application value in determining the extent of tumor resection. A total of 37
      patients with pituitary adenoma initially underwent tumor resection under an
      endoscope-assisted microscope via standard trans-nasal-sphenoidal approach, and
      tumor cavity structure was observed by applying the diving endoscopic technique.
      Surgery was subsequently performed again under a microscope or endoscope. The
      diving endoscopic technique allowed surgeons to directly observe the structure
      inside a tumor cavity in high-definition. In the present study, 24 patients had
      pituitary macroadenomas or microadenomas that did not invade the cavernous sinus,
      and were considered to have undergone successful total resection. Among these
      patients, no tumor residues were observed through the diving endoscopic
      technique. Some white lichenoid or fibrous cord-like tissues in the tumor cavity
      were considered to be remnants of tumors. However, pathology confirmed that these
      were not tumor tissues. For tumors that invaded the cavernous sinus in 13
      patients, observation could only be conducted under the angulation endoscope of
      the diving endoscope; i.e., the operation could not be conducted under an
      endoscope. The present study suggests that the diving endoscopic technique may be
      used to directly observe the resection extent of tumors within the tumor cavity,
      especially the structure of the tumor cavity inside the sella turcica. The
      present study also directly validates the reliability of pituitary adenoma
      resection under endoscope-assisted microscope. In addition, the diving endoscopic
      technique also allows the surgeon to observe the underwater environment within
      the sella turcica.

PMID- 29581740
TI  - Effects of low-level laser therapy following surgical extraction of the lower
      third molar with objective measurement of swelling using a three-dimensional
      system.
AB  - The aim of the present study was to evaluate and compare the effects of single-
      and two-dose low-level laser therapy (LLLT) on the postoperative swelling,
      trismus and pain of patients undergoing extraction of impacted mandibular third
      molars. In addition, edema was volumetrically measured with a 3dMD face system. A
      total of 45 patients were randomly divided into three treatment groups (15
      patients in each group) as follows: Group 1, receiving routine management with
      ice application and serving as the control group; Group 2, receiving a single
      dose of LLLT immediately following surgery; and Group 3, receiving two doses of
      LLLT, immediately following surgery and on day 2 after surgery. In the present
      study, a gallium-aluminum-arsenide (0.3 W, 40 sec, 4 J/cm2) diode laser device
      was applied extraorally at the insertion point of the masseter muscle. The
      trismus, pain level and facial swelling of the patients were evaluated. The
      visual analog scale (VAS) was used to examine the pain degree, while a 3dMD face
      photogrammetric system was used to evaluate the volumetric alterations of the
      swelling. The results indicated no statistically significant differences in the
      mean swelling or trismus among the three groups. The mean VAS measurements did
      not differ significantly among the groups at postoperative day 2; however,
      significantly reduced VAS values were observed in Group 2 compared with Group 1
      at postoperative day 7 (P<0.05). The present study demonstrated that, although
      single-dose or two-dose LLLT had beneficial effects on the swelling, trismus and
      pain level, a significant reduction was only observed in the pain level at
      postoperative day 7.

PMID- 29581741
TI  - Extract of Rhus verniciflua stokes protects against renal ischemia-reperfusion
      injury by enhancing Nrf2-mediated induction of antioxidant enzymes.
AB  - Ischemia-reperfusion injury (IRI) may cause acute kidney disease (AKD) by
      mediating the oxidative stress-induced apoptosis of parenchymal cells. The
      extract of Rhus verniciflua Stokes (RVS) is used as a traditional herbal medicine
      as it exhibits anti-oxidant, anti-apoptotic and anti-inflammatory properties.
      Therefore, the current study investigated the therapeutic effect and the
      underlying mechanism of RVS on IRI-induced AKD in vivo and in vitro. The current
      study assessed the effects of RVS on a mouse model of renal IRI and in hypoxic
      human renal tubular epithelial HK-2 cells. The results demonstrated that the IRI
      induced elevation of blood urea nitrogen, serum creatinine and lactate
      dehydrogenase was significantly attenuated by the intraoral administration of RVS
      (20 mg/kg/day) for 14 days prior to surgery. It was demonstrated that IRI surgery
      induced histological damage and cellular apoptosis in renal parenchyma, which
      were attenuated by pretreatment with RVS. Furthermore, in HK-2 cells incubated
      with 300 uM CoCl2 to induce chemical hypoxia, it was demonstrated that RVS
      treatment significantly inhibited cell death and the production of reactive
      oxygen species (ROS). Furthermore, RVS treatment upregulated the levels of
      endogenous antioxidant enzymes, including heme oxygenase-1 and catalase, as well
      as their upstream regulator nuclear factor erythroid 2-related factor 2, in HK-2
      cells. Taken together, these results suggested that the intraoral administration
      of RVS induces a therapeutic effect on IRI-induced AKD. These effects are at
      least partly due to the attenuation of ROS production via upregulation of the
      antioxidant defense system in renal tubular cells.

PMID- 29581742
TI  - Methylene blue relieves the development of osteoarthritis by upregulating lncRNA
      MEG3.
AB  - Methylene blue (MB) is a long-term inhibitor of peripheral nerve axons, thereby
      alleviating or permanently eliminating pain. However, it remains unknown whether
      MB is safe and effective method of treating osteoarthritis (OA). MB was injected
      into the knee joints of rabbits and they were monitored for any histological
      structural changes. The results revealed no evident changes in the histological
      structure of the normal knee joint following injection of 1 mg/kg MB at 1, 4, 8
      and 24 weeks post-injection. Compared with the vehicle control, MB treatment
      significantly enhanced the weight distribution and significantly decreased the
      swelling ratio of the rabbits. Additionally, levels of long non-coding RNA
      (lncRNA) maternally expressed 3 (MEG3) mRNA were significantly increased
      following treatment with MB, but the protein expression of P2X purinoceptor 3
      (P2X3) was significantly suppressed compared with the vehicle control. The levels
      of interleukin (IL) 6, tumor necrosis factor (TNF)alpha, IL-1beta and IL-8 were
      significantly suppressed following MB treatment, indicating that MB protects
      against OA progression. It was also revealed that MEG3 overexpression
      significantly suppresses levels of P2X3 protein. ELISA indicated that the MEG3
      induced reduction of IL-6, TNFalpha, IL-1beta and IL-8 expression was
      significantly reversed following P2X3 overexpression. Therefore, the results of
      the present study demonstrated that MB is an effective method of treating OA
      associated pain by upregulating lncRNA MEG3 levels. Additionally, lncRNA MEG3
      relieves the OA-associated pain and inflammation in a rabbit model of OA by
      inhibiting P2X3 expression.

PMID- 29581743
TI  - Tripterygium wilfordii mitigates hyperglycemia-induced upregulated Wnt/beta
      catenin expression and kidney injury in diabetic rats.
AB  - Aberrant activation of the Wnt/beta-catenin pathway contributes to the
      development of diabetic nephropathy (DN); however, treatment with Tripterygium
      wilfordii (TW) may be beneficial for patients with DN. The aim of the present
      study was to evaluate the effect of TW on Wnt/beta-catenin expression in the
      kidneys of diabetic rats. Male Sprague-Dawley rats were randomly injected with
      vehicle (control) or streptozotocin to induce diabetes. Diabetic rats were then
      randomly treated with vehicle (sodium carboxymethyl cellulose; SCC), TW combined
      with SCC (8 or 16 mg/kg) or irbesartan (50 mg/kg) daily for 8 weeks. Metabolic
      parameter levels and renal pathological changes were examined. mRNA and protein
      expression of Wnt-1, glycogen synthase kinase (GSK)-3beta, beta-catenin, nuclear
      factor (NF)-kappaB and transforming growth factor (TGF)-beta1 in the kidneys of
      rats from all groups were measured. Compared with the DM group, metabolic
      parameters and morphological parameters, apart from blood glucose levels, were
      significantly improved in TW-treated rats (all P<0.01). Furthermore, levels of
      Wnt-1, beta-catenin, NF-kappaB-p65 and TGF-beta1 mRNA and protein were
      significantly reduced in the kidneys of TW-treated rats compared with DM rats,
      whereas levels of GSK-3beta mRNA and protein did not differ significantly between
      any of the groups; however, the expression of P-GSK-3beta protein was
      significantly decreased in the kidneys of TW-treated rats compared with the DM
      group. The protective effects of TW tended to be dose-dependent and were an
      improvement compared with irbesartan treatment in diabetic rats. Therefore, the
      results of the present study indicated that treatment with TW mitigated
      hyperglycemia-induced upregulated Wnt-1 and beta-catenin expression in kidney
      tissues and ameliorated diabetes-induced kidney injury in rats.

PMID- 29581744
TI  - Protective effect of Atriplex suberecta extract against oxidative and apoptotic
      hepatotoxicity.
AB  - Atriplex suberecta I. Verd is a known phytomedicinal species of Atriplex;
      however, studies into its bioactivity remain inconclusive. The in vitro and in
      vivo antioxidative and hepatoprotective potential of A. suberecta ethanol-extract
      (ASEE) was assessed in the present study. 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging and beta-carotene bleaching assays revealed that ASEE possesses free
      radical scavenging and anti-lipid peroxidative activities. These results were
      supported by the in vitro protection of HepG2 hepatoblastoma cells via abating
      2,7-dichlorofluorescein-activated oxidative and apoptotic molecules (caspase-3/
      7). In carbon tetrachloride-treated rats, the oral administration of ASEE
      significantly normalized serum biomarkers of liver function (serum glutamate
      oxaloacetate, serum pyruvate transaminase, alkaline phosphatase, gamma-glutamyl
      transferase and bilirubin) and the lipid profile (total cholesterol, high-density
      lipoprotein, low-density lipoprotein, triglycerides and malondialdehyde),
      including tissue non-protein sulfhydryl and total protein levels. These results
      were also supported by liver histopathology, which demonstrated that the
      therapeutic effect of ASEE was comparable to silymarin. Furthermore,
      phytochemical analysis of ASEE revealed the presence of flavonoids, alkaloids,
      tannins and saponins. Rutin, an antioxidant flavonoid, was identified using the
      validated high-performance thin-layer chromatography method. In conclusion, this
      is the first report on the therapeutic potential of A. suberecta against chemical
      induced oxidative stress and liver damage.

PMID- 29581745
TI  - Rat vibrissa dermal papilla cells promote healing of spinal cord injury following
      transplantation.
AB  - Bone marrow mesenchymal stem cell (BMSC) transplantation is effective for
      repairing spinal cord injuries (SCIs); however, there are limitations of clinical
      BMSC applications. Previously, we reported that dermal papilla cells (DPCs)
      secrete brain-derived neurotrophic factor and glial cell line-derived
      neurotrophic factor more actively than BMSCs. To analyze the therapeutic function
      of DPCs in SCI, primary DPCs and BMSCs were cultured from the same green
      fluorescence protein-transgenic rat. The cells were suspended in rat-tail
      collagen I and transplanted separately into completely transected spinal cord
      lesion sites. Grafted-cell survival was examined with a small animal in vivo
      imaging detection system, and lesion sites were examined histochemically. In vivo
      imaging revealed enhanced lesion filling and survival with DPC grafts compared
      with BMSC grafts on days 14 and 21 post-transplantation. Hematoxylin and eosin
      staining demonstrated that lesion area sizes in the two groups were not markedly
      different. In the DPC transplant group, more axons formed within the lesion
      sites. CD31-positive vessel-like structures were more abundant in lesion sites
      near the grafted cells in the DPC group. The results of the present study suggest
      that DPCs may be a valuable alternative source of stem cells for autologous cell
      therapy for the treatment of SCI.

PMID- 29581746
TI  - Utility of dermoscopy for evaluating the therapeutic efficacy of tacrolimus
      ointment plus 308-nm excimer laser combination therapy in localized vitiligo
      patients.
AB  - The aim of the present study was to assess the function of dermoscopy in
      evaluating the therapeutic efficacy of tacrolimus ointment plus 308-nm excimer
      laser combination therapy in patients with localized vitiligo. A total of 147
      patients with localized vitiligo (progressive disease, n=92; stable period, n=55)
      were enrolled and received combination therapy for 12 weeks. The condition of the
      skin lesions was monitored by dermoscopy and visual observation. At the initial
      visit, skin lesions were observed in 61 progressive and 19 stable patients.
      Residual perifollicular pigmentation was more abundant in progressive-stage
      patients than in stable-stage patients, whereas the presence of perilesional
      hyperpigmentation was obviously lower in patients with progressive vitiligo.
      After 12 weeks of combination therapy, marked differences in residual
      perifollicular pigmentation were identified between the progressive- and stable
      stage patients. Dermoscopy and visual observation indicated that the 12-week
      treatment efficacy in patients with progressive disease was significantly higher
      than in those with stable disease and that assessment by dermoscopy was superior
      to visual observation at 8 or 12 weeks of treatment. Binary logistic regression
      analysis revealed that the disease stage, vitiliginous areas and disease course
      were risk factors associated with the treatment efficacy of the combination
      therapy. In conclusion, dermoscopy may be used as an effective means of vitiligo
      therapy assessment to provide an accurate and scientific evaluation of treatment
      efficacy for localized vitiligo patients.

PMID- 29581747
TI  - Gene expression analysis for pneumonia caused by Gram-positive bacterial
      infection.
AB  - Gram-positive bacteria are an important pathogenic factor for bacterial
      pneumonia. The aim of the present study was to identify the differentially
      expressed genes (DEGs) and to explore their associated pathways or expression
      patterns. Expression profiling of gene arrays from two independent datasets,
      GSE6269 and GSE35716, were downloaded from the Gene Expression Omnibus. The DEGs
      between peripheral blood samples from healthy controls and patients with
      bacterial pneumonia were identified. The Functional Annotation Tool in the
      Database for Annotation, Visualization and Integrated Discovery was used to
      annotate and analyze the DEGs in Gene Ontology (GO) terms and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) pathways. Multiple proteins were used to generate a
      protein-protein interaction (PPI) network. A total of 624 (621 annotated) were
      identified in the GSE6269 dataset and 398 (295 annotated) DEGs were identified in
      the GSE35716 dataset between pneumonia and healthy samples. A total of 40 common
      DEGs were identified between the 2 datasets, including 4 downregulated and 32
      upregulated DEGs. In the GO category cellular component, melanosome was highly
      enriched among 11 genes; in the category biological process, the three most
      enriched items were regulation of ruffle assembly, negative regulation of calcium
      ion transport and necroptotic process. In the KEGG terms, only the nuclear factor
      kappaB signaling pathway (Homo sapiens 04064) was significantly enriched. In the
      PPI network, five genes (CCL4, TIMP metallopeptidase inhibitor 1, intercellular
      adhesion molecule 1, plasminogen activator, urokinase receptor and cathepsin B)
      were identified to have a high degree of interaction with other DEGs. In
      conclusion, these five genes may represent key genes associated with pneumonia
      caused by Gram-positive bacteria. All of these results provide primary
      information and basic knowledge to understand the mechanisms of the pathogenesis.

PMID- 29581748
TI  - Osteoporosis as an initial manifestation in a patient with Crohn's disease: A
      case report.
AB  - The present case report details a rare case of osteoporosis as the initial
      manifestation of Crohn's disease (CD). A 43-year-old male was referred to the
      Second Xiangya Hospital of Central South University (Changsha, China) for further
      examination of low back pain (LBP) without digestive symptoms. Bone mineral
      density (BMD) analysis indicated osteoporosis, particularly in the lumbar spine.
      Endoscopy revealed an inflamed and strictured ileocecal valve with less
      inflammation in the ascending, transverse colon, sigmoid colon and rectum,
      compatible with CD, which was in accordance with the appearance of an abdominal
      computed tomography scan. Duodenal-balloon enteroscopy indicated segmental
      ulceration and stricture in the jejunum, in accordance with CD. The patient was
      diagnosed with CD following examination. It was suspected that osteoporosis may
      be an extra-intestinal manifestation of CD. Steroids and biological agents were
      prescribed in sequence. LBP and BMD rapidly improved following treatment, and
      inflammatory markers returned to normal after 1.5 years of treatment. According
      to this case, osteoporosis with unknown causes should be considered as a possible
      sign of small intestinal CD.

PMID- 29581749
TI  - Multiple pelvic accessory spleen: Rare case report with review of literature.
AB  - Accessory spleen (AS) usually presents as an isolated asymptomatic mass of
      splenic tissue separated from the body of the actual spleen. Multiple pelvic ASs
      are more unusual than single pelvic AS. The present study reported on the rare
      case of multiple pelvic AS. A 39-year-old Chinese woman presented at our hospital
      with complaints of abdominal pain for one week. A large pelvic mass behind the
      uterus was identified on ultrasound examination. Multiple AS in the pelvis was
      primarily considered during the operation and confirmed by histopathological
      examination after the surgery. The literature in English language was also
      reviewed by retrieving studies on AS published over the past 30 years, and it was
      discussed how to diagnose and treat pelvic AS. In conclusion, to the best of our
      knowledge, the present study provided the first case report of multiple pelvic
      AS. The gynecologist should be aware of the rare possibility of an AS in patients
      with abdominal and pelvic complaints and/or a pelvic mass. Pelvic AS is generally
      determined during radiological investigations or during open or laparoscopic
      surgeries.

PMID- 29581750
TI  - beta-Endorphin attenuates collagen-induced arthritis partially by inhibiting
      peripheral pro-inflammatory mediators.
AB  - The classical analgesic pathway of opioids by binding their receptors in the
      nervous system is well known. However, little is known regarding opioid analgesia
      through the anti-inflammatory pathway. The present study aimed to investigate the
      analgesic and anti-inflammatory effect of beta-endorphin on inflammatory pain. A
      rat model of collagen-induced arthritis (CIA) was generated by intradermal
      injection of bovine type II collagen. Rats were divided into the CIA + saline
      group and the CIA + beta-endorphin group, in which rats were intraperitoneally
      injected with beta-endorphin once every other day from day 18 following the
      injection of CII until day 28. Thermal hyperalgesia as determined by tail flick
      latency (TFL), as well as paw arthritis index and swelling. Tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta and IL-6 mRNA expression in synovial tissue
      and their protein levels in paw inflammatory tissue were measured. The rat CIA
      model was successfully induced as indicated by the significantly decreased TFL,
      increased paw arthritis index and percentage of swelling on day 18. beta
      endorphin treatment significantly increased the TFL, while decreasing the paw
      arthritis index and swelling in CIA rats. It also significantly downregulated TNF
      alpha and IL-1beta mRNA expression in synovial tissue and their protein levels in
      inflammatory tissue of the paws of CIA rats, while it had no significant effect
      on the levels of IL-6. These results indicated that beta-endorphin suppresses
      peripheral pro-inflammatory mediators in collagen-induced arthritis, which may
      contribute to its analgesic effect.

PMID- 29581751
TI  - Tumor suppressor miR-211-5p is associated with cellular migration, proliferation
      and apoptosis in renal cell carcinoma.
AB  - Increasing evidence has demonstrated that microRNA (miRNA) serve an important
      role in the tumorigenesis of various types of cancer, such as renal cell
      carcinoma (RCC). The expression of miR-211-5p has been detected in RCC tissue by
      microarray profiling. However, studies regarding miR-211-5p and RCC remain rare.
      In the present study, the expression of miR-211-5p in RCC tissues and cell lines
      was revealed to be downregulated by reverse transcription-quantitative polymerase
      chain reaction analyses. The present results also revealed that the upregulation
      or downregulation of miR-211-5p inhibited or promoted, respectively, RCC cell
      proliferation, migration and invasion. In addition, the upregulation or
      downregulation of miR-211-5p induced or inhibited, respectively, RCC cell
      apoptosis. However, the present study only identified that downregulation of miR
      211-5p promoted 786O and ACHN cell viability. The above results suggest that miR
      211-5p may be a tumor suppressor in the tumorigenesis of RCC and may be a
      potential therapeutic target for RCC in the future. Further research should focus
      on the underlying mechanism of miR-211-5p in RCC and on investigating the
      possible use of miR-211-5p as a biomarker for RCC.

PMID- 29581752
TI  - Enhanced antitumor activity of combined megestrol acetate and arsenic trioxide
      treatment in liver cancer cells.
AB  - Liver cancer is an aggressive malignancy with a very high fatality rate. Although
      megestrol acetate (MA) and arsenic trioxide (ATO) have shown an antitumor effect
      in liver cancer cells, the therapeutic benefits of MA or ATO alone in patients
      with liver cancer were limited. The aim of the present study was to elucidate
      whether the co-treatment of MA/ATO could enhance antitumor efficacy in liver
      cancer cell lines (Hep G2 and BEL 7402) and explore the underlying anti-cancer
      mechanisms. The cell viability, apoptotic response and expression levels of
      associated proteins were detected by Cell Counting Kit-8 assay, flow cytometry
      and western blotting, respectively. An xenograft model in nude mice bearing a Hep
      G2 tumor was used to estimate tumor growth in vivo. Co-treatment with MA/ATO
      markedly improved the inhibition of cell viability, enhanced apoptosis, and
      increased the phosphorylation of p38, c-Jun N-terminal kinase 1/2 and
      extracellular signal-regulated kinase 1/2 on liver cancer cell lines.
      Furthermore, the tumor growth in the murine Hep G2 cancer xenograft model was
      significantly inhibited by combined treatment with MA/ATO. The results indicated
      that MA/ATO combined treatment enhanced antitumor efficacy and possessed
      potential application for treating liver cancer.

PMID- 29581753
TI  - Knockdown of dickkopf2 inhibits vascular endothelia growth factor expression
      through the Wnt/beta-catenin signaling pathway in human retinal pigment
      epithelial cells under hypoxic conditions.
AB  - Hypoxia has been demonstrated to be a proangiogenic factor that induces vascular
      endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells.
      Dickkopf2 (DKK2), originally known as Wnt antagonist, has recently been
      demonstrated to have an important regulatory role in angiogenesis; however, the
      specific role of DKK2 in RPE cells is not known. In the present study, the
      effects of DKK2 on VEGF expression under hypoxic conditions were investigated, as
      well as the molecular mechanisms involved. The results demonstrated that the
      expression of DKK2 was markedly increased under hypoxic conditions compared with
      normoxic conditions. Knockdown of DKK2 markedly attenuated the CoCl2-induced
      expression of hypoxia-inducible factor (HIF)-1alpha and VEGF in RPE cells.
      Furthermore, knockdown of DKK2 markedly inhibited the expression of beta-catenin
      induced by hypoxia. In conclusion, the findings of the present study demonstrate
      that knockdown of DKK2 inhibits the hypoxia-induced production of VEGF by
      suppressing the activation of the Wnt/beta-catenin signaling pathway.

PMID- 29581755
TI  - FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis.
AB  - FOXG1, a member of forkhead family transcriptional factor, is involved in
      telencephalon development. Recent studies showed FOXG1 was important for a
      variety of cellular events in cancer cells. In respect to glioma, FOXG1 has been
      shown to regulate cell proliferation and cell cycles. However, its impacts on
      other cellular events were not well studied. Here, we found FOXG1 had high
      expression in clinical glioma tissues, and its expression positively correlated
      with glioma malignancy. Moreover, we found FOXG1 played roles in glioma cell
      apoptosis. The expressions of caspase family members were significantly altered
      in response to change of FOXG1 expression, indicating a direct regulation of
      FOXG1 on caspase family members. These data strongly suggest FOXG1 is negative
      regulator of glioma cell apoptosis.

PMID- 29581756
TI  - The Optimal Application of Transrectal Ultrasound in Staging of Rectal Cancer
      Following Neoadjuvant Therapy: A Pragmatic Study for Accuracy Investigation.
AB  - Background: Transrectal ultrasound (TRUS) is a cost-effective test for
      preoperative assessment of rectal cancer. However, whether the accuracy of TRUS
      staging is correlated with tumor location remains obscured. This study is
      designed to explore their relationship and confirm an optimal application of TRUS
      in rectal cancer restaging. Methods: From 2005 to 2011, rectal cancer patients
      with TRUS data were retrospectively reviewed. Patients were divided into five
      groups according to tumor-involved rectal segment (SEG) above the anal verge: SEG
      I 1-3cm, II 3-6cm, III 6-9cm, IV 9-12cm, and V 12-16cm. The accuracy and long
      term outcomes of tumor staging were compared between ultrasonographic and
      pathological stages. Results: 219 patients were included, with 55 (25.1%) in SEG
      I, 123 (56.2%) in SEG II, 32 (14.6%) in SEG III, 4 (1.8%) in SEG IV and 5 (2.3%)
      in SEG V. The overall accuracy of TRUS staging was remarkably superior to
      clinical staging by CT (64.8% vs. 34.7%, P<0.001), with 70.3% and 82.2% for
      ultrasonographic T and N stages respectively. The accuracy of TRUS reached its
      peak value when tumors were located in SEG II. The 5-year overall survival had no
      significant difference between TRUS and pathology staging for all stages. A cox
      regression analysis indicated that high levels of CEA and tumor location were
      risk factors of inaccurate staging. Conclusions: TRUS is still a valuable
      examination for restaging of rectal cancer after neoadjuvant therapy. The
      application of TRUS would be optimal for rectal cancer located 3-6cm above the
      anal verge.

PMID- 29581754
TI  - Exosomes in Nasopharyngeal Carcinoma.
AB  - Exosomes are nanosized (30-100nm) membrane microvesicles secreted through a
      complex cellular process. Exosomes contain a variety of bioactive molecules, such
      as proteins, microRNAs(miRNAs or miRs) and long non-coding RNAs (lncRNAs),
      playing an important role in the cell-to-cell substance transportation and signal
      transduction. Nasopharyngeal carcinoma-related exosomes (NPC-Exo) have been
      identified in circulating blood and contribute to tumor cell proliferation,
      angiopoiesis, and immune tolerance through remodeling of tumor microenvironment
      (TME). Nasopharyngeal carcinoma-related exosomes may also induce epithelial
      mesenchymal transition (EMT), thus promoting tumor metastasis and
      chemoradioresistance. Clinically, the exosomes may serve as novel biomarkers for
      diagnosis and targeted therapies of nasopharyngeal carcinoma. This review article
      updates the understanding of exosomes in nasopharyngeal carcinoma(NPC).

PMID- 29581757
TI  - Serum expression level of IL-6 at the diagnosis time contributes to the long-term
      prognosis of SCLC patients.
AB  - Cytokines are vital mediators involved in tumor immunity. We aimed to explore
      whether the expression levels of IL-1beta, TNF-alpha and IL-6 have impacts on
      prognosis of SCLC patients. In this study, we concluded 707 non-operable SCLC
      patients at stage III or IV into this study and analyzed the relationships
      between interleukins and OS/PFS by cox regression analysis and Kaplan-Meier
      analysis (log-rank test). As a result, under current standard chemotherapy, SCLC
      patients with higher IL-6 expression level had a shortened OS compared with those
      with normal level (HR: 0.381, 95%CI: 0.177-0.822, p=0.014). Furthermore, IL-6
      expression level contributed mostly to patients without a smoking history. Non
      smoking patients with a high IL-6 level showed a 6 months shortened OS than those
      with normal IL-6 level (10.50 vs 16.90 months, p=0.003 by Log-Rank test in Kaplan
      Meier analysis). IL-6 had no obvious impacts on first-line PFS in these SCLC
      patients. To conclude, IL-6 acts as an independent factor of long-term prognosis
      of SCLC patients under current therapy.

PMID- 29581758
TI  - A Prognostic Score for Nasopharyngeal Carcinoma with Bone Metastasis: Development
      and Validation from Multicenter.
AB  - Background: To establish a prognostic score based on clinical routine factors to
      stratify nasopharyngeal carcinoma patients with bone metastasis into risk groups
      with different survival rates. Materials and Methods: Total 276 patients from
      multicenter were retrospectively analyzed. Kaplan-Meier method and Cox regression
      were used to confirm independent risk factors, which were checked for internal
      validity by bootstrapping method. The prognostic score, deriving from the
      corresponding regression coefficients in Cox model, classified patients into low
      and high risk groups. Finally, two independent cohorts were used for external
      validation. Results: In development cohort, six risk factors were identified:
      age>46 year-old (point=1), N>0 stage (point=2), anemia (point=2), bone metastasis
      free interval<=12 months (point=1), without radiotherapy to primary sites
      (point=1), and without radiotherapy to first metastasis sites (point=1). The
      derived prognostic score divided patients into low (score, 0-4) and high (score,
      5-8) risk groups, with highly significant differences of 5-year overall survival
      rates (high vs. low risk: 24.6% vs. 58.2%, HR 3.47, P<0.001). Two external
      validations presented congruent results. Conclusion: A feasible and applicative
      prognostic score was successfully established and validated to discriminate bone
      metastatic nasopharyngeal carcinoma into low/high risk groups, which will be
      useful for individual treatment.

PMID- 29581759
TI  - The value of preoperative Glasgow Prognostic Score and the C-Reactive Protein to
      Albumin Ratio as prognostic factors for long-term survival in pathological T1N0
      esophageal squamous cell carcinoma.
AB  - Plenty of studies have confirmed the prognostic values of inflammation-based
      prognostic scores in many malignant tumors. In present study, we aim to explore
      whether these indexes has same prognostic values in patients with stage T1N0
      esophageal squamous cell carcinoma (ESCC). The clinicopathological data of 160
      consecutive patients with pathological stage T1N0 ESCC from January 2005 to
      December 2012 were collected retrospectively. As prognostic factors, the
      inflammation-based prognostic scores, including C-reactive protein (CRP), Glasgow
      prognostic score (GPS), prognostic index (PI), neutrophil to lymphocyte ratio
      (NLR), platelet to lymphocyte ratio (PLR) and CRP to albumin ratio (CAR), were
      evaluated. The best cut-off values were determined by the receiver operating
      characteristic (ROC) curves. The median follow-up time was 71.8 months. During
      the follow-up period, 34 (21.3%) patients occurred postoperative recurrence and
      30 (18.8%) tumor-related deaths were recorded. The best cut-off values of CRP,
      NLR, PLR and CAR were 1.090, 1.976, 103.200 and 0.023, respectively. After
      multivariate analysis, the GPS and CAR were identified as independently
      prognostic factors for overall survival (OS) (p=0.017 and 0.040, respectively).
      Of all 160 individuals, there were 86 (53.8%) and 85 (53.1%) patients classified
      into high GPS group (1-2) and elevated CAR group (>0.023), respectively. In
      addition, the GPS were positively associated with PI (p<0.000) and the levels of
      serum CRP (p<0.000), NLR (p=0.004), PLR (p=0.029) and CAR (p<0.000) and the above
      correlations were also observed between the CAR and other inflammation-based
      prognostic scores (all p<0.050, except for p=0.054 for PLR levels). The
      preoperative GPS and CAR were simple, inexpensive, readily available predictor
      for long-term survival in stage T1N0 ESCC patients who underwent esophagectomy.

PMID- 29581760
TI  - A New and Safe Mode of Ventilation for Interventional Pulmonary Medicine: The
      Ease of Nasal Superimposed High Frequency Jet Ventilation.
AB  - We use pulmonary interventional procedures for the diagnosis of pulmonary
      diseases either for benign or malignant lesions. Flexible bronchoscopy with or
      without radial endobronchial ultrasound, convex-probe endobronchial ultrasound
      and electromagnetic navigation are procedures performed in centers with
      experience in diagnostic pulmonary medicine. The method of sedation and
      ventilation is very important in order to avoid or handle with success
      complications. Proper respiration during pulmonary (or other interventional)
      procedures is a key factor. Apart from the proper sedation method we have to
      choose the proper ventilation method which decides respiratory movement.
      Superimposed high-frequency jet ventilation (SHFJV) is supposed to be safe and
      effective in clinical practice. Although this perception is commonly accepted,
      there is no study proving its safety on the basic of reliable data. We analyzed
      the data of 100 patients in different interventional settings (bronchoscopy with
      or without navigational approach, left atrial appendage closure (LAAC) or
      intracardiac catheterization) using nasal SHFJV. Mainly analyzed were capillary
      ABG-Data at the beginning and end of the intervention under sedation. The aim was
      to analyze if a risk scenario for the patient by using the nasal SHFJV can be
      derived by measuring the changes of pCO2, pO2, cBase Excess, cHCO3 and PH. Due to
      our data we conclude that this method of ventilation can be easily and safely
      used in interventional medicine for patients with all kind of comorbidities such
      as; chronic respiratory disease, lung cancer, interstitial lung disease,
      structural heart disease and heart failure.

PMID- 29581761
TI  - Discrimination between malignant and benign mass-like lesions from breast dynamic
      contrast enhanced MRI: semi-automatic vs. manual analysis of the signal time
      intensity curves.
AB  - Purpose: To investigate the performance of a new semi-automatic method for
      analyzing the signal time-intensity curve (TIC) obtained by breast dynamic
      contrast enhancement (DCE)-MRI. Methods: In the conventional method, a circular
      region of interest was drawn manually onto the map reflecting the maximum slope
      of increase (MSI) to delineate the suspicious lesions. The mean TIC was
      determined subjectively as one of three different wash-out patterns. In the new
      method, the lesion area was identified semi-automatically. The mean TIC was
      categorized quantitatively. In addition to the MSI, other quantitative parameters
      were calculated, including the signal intensity slope (SIslope), initial
      percentage of enhancement (Einitial), percentage of peak enhancement (Epeak),
      early signal enhancement ratio (ESER), and second enhancement percentage (SEP).
      The performances were compared with receiver operating characteristic (ROC)
      analysis and Wilcoxon's test. Results: For TIC categorization results, the
      diagnostic accuracy rates were 61.54% with the traditional manual method and
      76.92% with the new method. For the mean MSI values from the manual method, the
      accuracy was 63.41%. For the mean TIC derived using the semi-automatic method,
      the diagnostic accuracy were 82.05% for SIslope, 67.31% for MSI, 61.53% for
      Einitial, 64.75% for Epeak, 64.74% for ESER, and 52.56% for SEP, respectively.
      For the lesion regions identified by the semi-automatic method, the diagnostic
      accuracy for above mentioned parameters were 80.13%, 69.87%, 61.54%, 63.47%,
      64.74% and 55.13%, respectively. Conclusion: With respect to the analysis of TIC
      from breast DCE-MRI, the results demonstrated that the new method increased the
      diagnostic accuracy, and should be considered as a supplementary tool for
      distinguishing benign and malignant lesions.

PMID- 29581762
TI  - Ring finger protein 38 promote non-small cell lung cancer progression by endowing
      cell EMT phenotype.
AB  - Objectives: Ring finger protein 38 (RNF38), as an E3 ubiquitin ligase, plays an
      essential role in multiple biological processes by controlling cell apoptosis,
      cell cycle and DNA repair, and resides in chromosome 9 (9p13) which is
      involvement in cancer pathogenesis including lung cancer. However, its function
      in tumorigenesis remains unclear. Hence, this study set out to investigate the
      biological function and clinical implications of RNF38 in non-small cell lung
      cancer (NSCLC). Materials and Methods: Immunohistochemistry, quantitative real
      time polymerase chain reaction (qRT-PCR) and western blot were used to detect
      RNF38 protein and mRNA levels in NSCLC and corresponding paratumor tissues.
      Tissue microarrays (TMA) analysis of 208 NSCLC cases were used to evaluate the
      relationship between RNF38 expression and clinical implications. Prognostic value
      was assessed by Kaplan-Meier analysis and log-rank tests. Wound-healing assays,
      trans-well assays, colony formation assays and CCK8 were used to assess cell
      migration, invasion and proliferative ability respectively. The analysis of
      epithelial-to-mesenchymal transition (EMT) phenotype was carried out by
      immunofluorescence and western blot. Results: Our data revealed that elevated
      RNF38 expression were more common in NSCLC tissues than paired normal tissues in
      both mRNA (2.82 +/- 0.29 vs. 1.23 +/- 0.13) and protein (2.75 +/- 0.09 vs. 1.24
      +/- 0.02) level. High levels of RNF38 expression were significantly associated
      with lymph node metastases, higher TNM stages (p=0.011), larger tumor size
      (p=2.09E-04) and predicted poor prognosis. RNF38 expression was inversely
      correlated with E-cadherin expression (P= 0.025). Moreover, downregulation of
      RNF38 impaired the proliferation, metastatic and invasive abilities in NSCLC
      cells. In addition, aberrant RNF38 expression could modulate the key molecules of
      EMT. Conclusions: Our results indicate that elevated expression of RNF38 is
      significantly associated with the proliferation and metastatic capacity of NSCLC
      cells, and RNF38 overexpression can serve as a biomarker of NSCLC poor prognosis.

PMID- 29581763
TI  - Cancer survival in patients from a hospital-based cancer registry, China.
AB  - Purpose: There are few reports on survival rate analysis from hospital-based
      cancer registries (HBCR) in China, although the National Center of Cancer
      Registry of China has launched such an effort with the mission to expand the
      scope of registration and follow-up. Our study aimed to evaluate survival and
      outcomes of cancer patients from a HBCR in eastern China. Methods: Active and
      passive follow-up methods were used to obtain information on survival status for
      all patients from Qidong City and Haimen City in the databases of our hospital
      based registrations from 2002 to 2014. Censor time for survival was 31st March,
      2016. Survival probability was estimated using the life-table method with SPSS
      Statistics software, and comparison of significant differences in survival rates
      was tested by Wilcoxon (Gehan) statistic. Results: The outcomes of 5010 patients
      were identified in the follow-up for 5244 cases from Qidong and Haimen, with a
      follow-up rate of 95.65%, and a rate of lost to follow-up of 4.35%. The 1-, 3-, 5
      , and 10-year observed survival (OS) rate in all-combined cancer sites were
      59.80%, 37.70%, 30.82%, and 22.60%, respectively. The top 10 cancer sites in rank
      were cancers of lung, esophagus, liver, cervix, stomach, breast, colon-rectum,
      non-Hodgkin's lymphoma, nasopharynx, and ovary, with 5-year OS rates of 12.63%,
      19.62%, 11.69%, 66.61%, 21.35%, 59.43%, 36.36%, 37.03%, 48.95% and 36.17%,
      respectively. Females experienced better survival than males for lung,
      esophageal, liver, nasopharyngeal and pancreatic cancers (P<0.05), but not for
      other sites (P>0.05). A significant difference was also found between males and
      females when all-sites were combined (P<0.01). There are significant differences
      (P<0.05) between the 2015 patients (from Qidong) and the 3001 patients (from
      Haimen) with 5-year OS rates of 32.72% vs 29.57%; no significant differences were
      found for 5-year OS rates for individual cancer sites (P>0.05) except for liver
      (P=0.0005) and ovary (P=0.0460) between the two cities. Younger patients had
      better prognosis, but significance was only seen in cervical (P=0.0102) and
      nasopharyngeal (P=0.0305) cancers. Conclusion: The survival rates of each site or
      of all sites-combined in this setting are consistent with those elsewhere in
      China and abroad. Discrepancies in overall survival could be affected by the
      proportion of sites with or without better prognosis. Hospital-based cancer
      survival is a better index to evaluate outcomes that reflect the levels of
      comprehensive treatment and improvement of medical and health services.

PMID- 29581764
TI  - The value of neutrophil-to-lymphocyte ratio for response and prognostic effect of
      neoadjuvant chemotherapy in solid tumors: A systematic review and meta-analysis.
AB  - Introduction: The neutrophil-to-lymphocyte ratio (NLR) has been found to be an
      indicator of poor prognosis in many tumour types. However, little is known about
      the relationship between the NLR and patients with tumours who receive
      neoadjuvant chemotherapy (NAC) in terms of response rate and prognostic ability.
      We thus performed this meta-analysis to further investigate this relationship.
      Methods: An electronic systematic literature search for articles published before
      September 2017 was performed to explore the association between the pretreatment
      NLR and outcome in patients treated with NAC. Data were extracted by the reported
      odds ratios (ORs) and hazard ratios (HRs) with their 95% confidence intervals
      (CIs) for the response rate and the survival outcome, respectively. The results
      were pooled using the random-effect or fixed-effect model. Results: Thirty-three
      studies were eventually included in our study, and all were published no earlier
      than 2011. An NLR that was higher than the cut-off was associated with a lower
      pathological complete response (pCR) rate in patients with cancer (OR = 1.72, 95%
      CI, 1.26-2.33). A lower NLR was associated with better overall survival (OS) (HR
      = 1.58, 95% CI, 1.34-1.86), cancer-specific survival (CSS) (HR = 2.22, 95% CI,
      1.32-3.74), disease-free survival (DFS) (HR = 1.32, 95% CI, 1.10-1.59) and
      recurrence-free survival (RFS) (HR = 1.90, 95% CI, 1.50-2.40). Conclusion:
      Overall, an NLR lower than the cut-off value indicated a greater chance for pCR
      and may predict good survival outcomes after NAC for patients with solid tumours.
      The use of the NLR for risk stratification before NAC should be further
      demonstrated by future large-scale prospective studies.

PMID- 29581765
TI  - Overall survival and post-progression survival are potent endpoint in phase III
      trials of second/third-line chemotherapy for advanced or recurrent epithelial
      ovarian cancer.
AB  - Purpose: A growing number of treatment options and active compounds in treatments
      have led to better outcomes for patients with advanced or recurrent epithelial
      ovarian cancer. We examined the association between progression-free survival
      (PFS), post-progression survival (PPS) and overall survival (OS) in phase III
      trials of second- and third-line chemotherapy for advanced or recurrent
      epithelial ovarian cancer. We aim to determine whether PFS or PPS is a surrogate
      of OS so that we can decide progress of disease is optimal endpoint for ovarian
      cancer. Methods: We identified 22 trials conducted between January 1, 2000
      through December 31, 2014 by literature search. We divided OS into PFS and PPS,
      and assessed the association between OS and PFS/PPS. We also examined whether the
      year of trial enrollment completion was associated with any variables. Results:
      The median PPS was slightly longer in recent trials compared to older trials
      (10.0 vs. 8.8 months). While PPS was strongly associated with OS (r = 0.88) in
      all trials, PFS was moderately correlated with OS (r = 0.72). The correlation
      between OS and PPS in recent trials (r = 0.93) was stronger than in older trials
      (r = 0.84). Conclusions: Our findings indicate that PPS is highly associated with
      OS in second/third-line chemotherapy for advanced or recurrent epithelial ovarian
      cancer, while the association between PFS and OS is moderate. We recommend using
      OS as primary endpoint for clinical trial of ovarian cancer, however PFS is still
      an optional endpoint.

PMID- 29581766
TI  - Large Intergenic Non-coding RNA-RoR Inhibits Aerobic Glycolysis of Glioblastoma
      Cells via Akt Pathway.
AB  - Reprogramming energy metabolism is a hallmark of malignant tumors, including
      glioblastoma (GBM). Aerobic glycolysis is often utilized by tumor cells to
      maintain survival and proliferation. However, the underlying mechanisms of
      aerobic glycolysis in GBM remain elusive. Herein, we demonstrated that large
      intergenic non-coding RNA-RoR (LincRNA-RoR) functioned as a critical suppressor
      to inhibit the aerobic glycolysis and viability of GBM cells. We found that
      LincRNA-RoR was markedly reduced in GBM tissues compared with adjacent non-tumor
      tissues from 10 cases of GBM patients. Consistently, LincRNA-RoR expression in
      GBM cells was significantly lower than that in normal glial cells. The aerobic
      glycolysis of GBM cells, as determined by the measurement of glucose uptake and
      lactate production, was impaired by LincRNA-RoR overexpression. Mechanistically,
      LincRNA-RoR inhibited the expression of Rictor, the key component of mTORC2
      (mammalian target of rapamycin complex 2), to suppress the activity of Akt
      pathway and impair the expression of glycolytic effectors, including Glut1, HK2,
      PKM2 and LDHA. Finally, enforced expression of LincRNA-RoR reduced the
      proliferation of GBM cells in vitro, restrained tumor growth in vivo, and
      repressed the expression of glycolytic molecules in GBM xenografts. Collectively,
      our results underscore LincRNA-RoR as a new suppressor of GBM aerobic glycolysis
      with therapeutic potential.

PMID- 29581767
TI  - Inhibition of PI3K/AKT Signaling Pathway Radiosensitizes Pancreatic Cancer Cells
      with ARID1A Deficiency in Vitro.
AB  - Pancreatic cancer is among the most aggressive human cancers, and is resistant to
      regular chemotherapy and radiotherapy. The AT-rich interactive domain containing
      protein 1A (ARID1A) gene, a crucial chromatin remodeling gene, mutates frequently
      in a broad spectrum of cancers, including pancreatic cancer. Recent evidence
      suggests that ARID1A acts as tumor suppressor and plays an important role in DNA
      damage repair (DDR). However, the effect of ARID1A on the radiosensitivity of
      pancreatic cancer remains unclear. Herein, we investigated the involvement of
      ARID1A depletion in the radioresistance of pancreatic cancer cells, and explored
      the underlying mechanisms. The results reveal that knockdown of ARID1A enhances
      the radioresistance of pancreatic cancer cells through suppressing apoptosis,
      impairing G2-M checkpoint arrest, strengthening DDR, and accompanying activation
      of PI3K/AKT signaling pathway. Moreover, upon inhibition of PI3K/AKT pathway by
      PI3K-inhibitor LY294002 or AKT-inhibitor mk2206, the radiosensitivity of ARID1A
      deficient pancreatic cancer cells is improved in vitro via increased apoptosis
      and weakened DDR. Taken together, these data suggest that loss of ARID1A
      expression enhances radioresistance of pancreatic cancer through activation of
      PI3K/AKT pathway, which maybe a promising target for radiosensitization of ARID1A
      deficient pancreatic cancer.

PMID- 29581768
TI  - Characteristics and Treatment of Brain Metastases from Esophageal Squamous Cell
      Carcinoma.
AB  - Brain metastasis is very rare in esophageal squamous cell carcinoma (ESCC). We
      retrospectively analyzed 4494 patients diagnosed with ESCC between 2010 and 2015
      at a single institute; 15 of these patients developed brain metastases. All 15
      patients had neurologic symptoms and were diagnosed by imaging or biology. Of the
      15 patients, 67% had a solitary brain lesion and 73% had lesions larger than 3
      cm. After treatment of the brain lesions, including surgery (53%) or stereotactic
      radiotherapy with or without whole brain radiation (20%), the median progression
      free survival time and the 2-year overall survival rate calculated from diagnosis
      of brain metastasis were 14.4 months and 36%, respectively. A graded prognostic
      assessment (GPA) score > 2.0 was associated with significantly better overall
      survival. Patients with brain metastases from ESCC achieve good overall survival
      after appropriate treatment of the brain lesion(s); GPA score may represent a
      prognostic factor for treatment decision-making.

PMID- 29581769
TI  - Alteration of Serum IgG Galactosylation as a Potential Biomarker for Diagnosis of
      Neuroblastoma.
AB  - Background: Neuroblastoma (NB) is the most frequent pediatric malignant neoplasm
      that originates from embryonic neural crest cells. Urinary catecholamines in 24-h
      urine are most commonly analyzed for the diagnosis of neuroblastoma at good
      sensitivity; however, it is challenging to collect 24-h urine samples in a
      pediatric population. Therefore, development of more rapid, non-invasive and cost
      effective tools for the diagnosis of NB remains needed. Serum immunoglobulin G
      (IgG) galactosylation have been found highly associated with adult cancers in our
      previous study. Methods: To explore the potential use of serum IgG
      galactosylation in aiding diagnosis of neuroblastoma, serum IgG galactosylation
      profiles of 26 neuroblastoma cases and 30 age-matched non-malignant controls were
      analyzed by MALDI MS. The alteration of IgG galactosylation in neuroblastoma
      patients was measured by a Gal-ratio formula: G0/(G1+G2*2), calculating the
      relative intensities of agalactosylated N-glycan (G0) vs mono-galactosyl N-glycan
      (G1) and digalactosyl N-glycan (G2). Results: The results showed that IgG Gal
      ratios were significantly higher in neuroblastoma cases compared with non
      malignant controls (p=5.0*10-4). And the Gal-ratio data generated sensitivity and
      specificity of 84.62% and 60.00%, combined with an AUC (area under the curve) of
      0.80. Conclusions: The analysis of serum IgG galactosylation distribution may
      play a suggestive role for neuroblastoma diagnosis, or serve as a potential
      biomarker for NB diagnosis.

PMID- 29581770
TI  - Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase
      inhibitor Danusertib.
AB  - Background: To elucidate the expression of Aurora kinases (AURK) and the
      anticancer effects of pan-aurora kinase inhibitor Danusertib in
      hepatocarcinogenesis model in C56Bl6 mice. Methods: Thirty mice C56Bl6 were
      randomly divided into Group A or control, Group B animals who underwent
      experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C
      animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora
      kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC)
      included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF
      kappaB p65, c-Jun, beta-catenin. Hepatocyte growth factor receptor (C-MET/HGFR)
      and Bcl-2 antagonist of cell death (BAD) serum levels were determined using a
      quantitative sandwich enzyme immunoassay technique. Results: Inhibition of AURK
      reduced the number of DEN-induced liver tumours. Apoptosis and proliferation was
      very low in both DEN-induced and anti- AURK groups respectively. The
      hepatocellular adenoma cells of DEN-treated mice uniformly had ample nuclear
      INCENP whereas in anti- AURK markedly decreased. Expression of beta-catenin, NF
      kB and c-Jun did not differ in liver tumors of both AURK -depleted and non
      depleted mice. Conclusions: Depletion of AURK reduced the number of DEN-induced
      hepatic tumours. However, their size did not differ significantly between the
      groups.

PMID- 29581771
TI  - Genome-wide Association Study (GWAS) of Germline Copy Number Variations (CNVs)
      Reveal Genetic Risks of Prostate Cancer in Chinese population.
AB  - Introduction: The associations between Prostate cancer (PCa) and germline copy
      number variations (CNVs) in genome-wide level based on Chinese population are
      unknown. The objective of this study was to identify possible PCa-risk associated
      CNV regions in Chinese population. Materials and Methods: We performed a genome
      wide association study for CNV in 1,417 PCa cases and 1,008 controls in Chinese
      population. Results: 7 risk-associated CNVs were identified for PCa after
      association analyses (P <7.2*10-6). Another 34 CNVs were found to be potentially
      risk-associated CNVs (P<0.05). Among the total 41 CNVs, 27 CNVs were risk
      variations and the other 14 were found to be protective of PCa. 25 of the CNVs
      (19 duplications and 6 deletions) were located in gene regions while 16 CNVs (9
      duplications and 7 deletions) were located in intergenic regions. We identified a
      higher burden of gaining PCa-risk CNVs and a lower frequency of protective CNVs
      in cases than controls. Bioinformatics analyses suggested that genes related to
      PCa risk-associated CNVs were significantly enriched in some biological
      processes, cellular components and molecular functions. Conclusion: These results
      provided additional information of genetic risks for PCa. Several CNV regions
      involved actionable genes that might be potential gene for target therapy.
      Additional validation and functional studies are warranted for these results.

PMID- 29581772
TI  - CXCR4/CXCR7/CXCL12-Axis in Follicular Thyroid Carcinoma.
AB  - Background: Follicular thyroid carcinoma's (FTC) often benign course is partially
      due to adjuvant radioactive iodine (RAI) treatment. However, once the tumour has
      spread and fails to retain RAI, the therapeutic options are limited and the
      outcome is poor. In this subset of patients, the identification of novel
      druggable biomarkers appears invaluable. Here, we investigated the stage
      dependent expression and functional role of the C-X-C chemokine receptors type 4
      and 7 (CXCR4/7) in FTC. Methods: CXCR4/7 expression was examined in 44 FTC and
      corresponding non-neoplastic thyroid specimens as well as 10 FTC distant
      metastases and 18 follicular adenomas using tissue microarray technology.
      Expression levels were correlated with clinicopathological variables as well as
      overall and recurrence free survival. Changes regarding cell cycle activation,
      tumour cell invasiveness and mRNA expression of genes related to epithelial
      mesenchymal transition (EMT) were investigated after treatment with recombinant
      human SDF1alpha/CXCL12 (rh-SDF1alpha) and CXCR4 antagonists AMD3100 and WZ811.
      Results: CXCR4/7 expression was associated with large tumour size, advanced UICC
      stage as well as shorter overall and recurrence free survival. CXCR4 was
      significantly higher expressed in distant metastases than in primary tumour
      cores. In addition, rh-SDF1alpha induced invasive growth, cell cycle activation
      and EMT, while CXCR4 antagonists significantly reduced FTC invasiveness in vitro.
      Conclusion: Here we provide first evidence of the biological importance of the
      CXCR4/CXCR7/CXCL12 axis in FTC. Our findings underscore the therapeutic potential
      of this chemokine receptor family in advanced FTC and offer new valuable insight
      into the oncogenesis of metastatic FTC.

PMID- 29581773
TI  - Epigenetic modification of SALL1 as a novel biomarker for the prognosis of early
      stage head and neck cancer.
AB  - This study examined Sal-like protein (SALL)1 methylation profiles in head and
      neck squamous-cell carcinoma (HNSCC) patients at diagnosis and follow-up, and
      evaluated their prognostic significance and value as a biomarker. SALL1
      expression was examined in a panel of cell lines by quantitative reverse
      transcription PCR (qRT-PCR). Promoter methylation was determined by quantitative
      methylation-specific polymerase chain reaction (qMSP) and was compared to the
      clinical characteristics of 205 samples. SALL1 promoter methylation was
      associated with transcriptional inhibition and was correlated with disease
      recurrence in 31.7% of cases, with an odds ratio of 1.694 (95% confidence
      interval: 1.093-2.626; P = 0.018) by multivariate Cox proportional hazard
      regression analysis. SALL1 promoter hypermethylation showed highly discriminatory
      receiver operator characteristic curve profiles that clearly distinguished HNSCC
      from adjacent normal mucosal tissue, and was correlated with reduced disease-free
      survival in early stage T1 and T2 patients (log-rank test, P < 0.001). SALL1
      methylation was significantly correlated with the methylation status of both
      SALL3 and CDH1. This study suggests that CpG hypermethylation is a likely
      mechanism of SALL1 gene inactivation, supporting the hypothesis that SALL1 might
      play a role in HNSCC tumorigenesis and could serve as an important biomarker.

PMID- 29581774
TI  - Tumor location is an independent predictive factor for distant metastasis and
      metastatic sites of rectal adenocarcinoma in patients receiving total mesorectal
      excision.
AB  - Background and Objectives: To evaluate the predictive factor for and patterns of
      distant metastasis in patients with rectal adenocarcinoma receiving total
      mesorectal excision (TME). Methods: We enrolled 217 consecutive patients who had
      histologically confirmed rectal adenocarcinoma and underwent surgery at Taipei
      Medical University- Wanfang Hospital between January 2000 and December 2014. TME
      was performed in all patients undergoing a sphincter-sparing procedure or
      abdominal perineal resection of rectal cancer. We performed univariate and
      multivariate Cox regression analyses of the distant metastasis rate in all
      patients to evaluate predictive factors. Overall survival (OS) rates were
      calculated using the Kaplan-Meier method, and Kaplan-Meier survival curves were
      compared using the log-rank test. Results: A multivariate Cox regression analysis
      of the distant metastasis rate in patients with rectal adenocarcinoma identified
      tumor locations and American Joint Committee on Cancer (AJCC) stages as
      prognostic risk factors. The adjusted hazard ratios (aHRs) of distant metastasis
      for the upper-third, middle-third, and AJCC stage I-II cancers were 0.08 (95% CI,
      0.01-0.69; p = 0.021), 0.41 (95% CI, 0.15-0.99; p = 0.047), and 0.20 (95% CI,
      0.10-0.66; p = 0.008), respectively. The 5-year lung metastasis rates among
      patients with upper-, middle-, and lower-third rectal cancers were 0%, 3.37%, and
      13.33%, respectively (log-rank, p = 0.001), and the 5-year liver metastasis rates
      among patients with upper-, middle-, and lower-third rectal cancers were 2.12%,
      9.10%, and 11.76%, respectively (log-rank, p = 0.096). The 5-year OS rates also
      differed with different rectal adenocarcinoma locations. The 5-year OS rates for
      upper, middle, and lower rectal cancers were 96%, 86%, and 64%, respectively (log
      rank, p < 0.001). Conclusion: A poor OS rate and high lung or liver metastasis
      rate were observed in distal rectal adenocarcinoma. Longer intensive surveillance
      of the chest, abdomen, and pelvis after TME in distal rectal adenocarcinoma could
      be necessary.

PMID- 29581775
TI  - Increased Paxillin expression in prostate cancer is associated with advanced
      pathological features, lymph node metastases and biochemical recurrence.
AB  - Purpose Paxillin regulates cell-cell adhesion, and altered Paxillin expression
      has been associated with human carcinogenesis. This study analyzed the
      association between Paxillin expression in prostate cancer (PCa) tissues with
      clinicopathological features, lymph node metastasis and biochemical PCa
      recurrence. Methods A total of 386 tissue specimens from PCa patients who
      received radical prostatectomy and 60 tissue specimens from benign prostatic
      hyperplasia (BPH) cases were collected to construct tissue microarrays, which
      were subsequently immunostained for Paxillin expression. Thirty positive lymph
      node tissue specimens and 10 healthy prostate tissue specimens were randomly
      selected for Paxillin immunostaining. Results The association between Paxillin
      expression, lymph node metastasis and biochemical PCa recurrence was analyzed.
      Paxillin expression was significantly higher in PCa than both normal and BPH
      tissues (P<0.001) and was correlated with preoperative prostate-specific antigen
      level, Gleason score, clinical tumor stage, lymph node metastasis, positive
      surgical margin, extracapsular extension and seminal vesicle invasion (P<0.05 for
      all). Logistic regression analysis showed that Paxillin and Gleason score were
      independent risk factors for PCa lymph node metastasis (P<0.05). The receiver
      operating characteristic (ROC) curve indicated that Paxillin expression
      (AUC=0.723) more accurately predicted PCa lymph node metastasis than Gleason
      score (AUC=0.692). Kaplan-Meier curve analysis showed that increased Paxillin
      expression was associated with shortened biochemical-free survival (BFS) after
      radical prostatectomy (P<0.001). Conclusion Paxillin was significantly
      upregulated in PCa compared with BPH and normal tissues and associated with lymph
      node metastasis and shortened BFS of PCa. Further study will investigate the
      underlying molecular mechanism and the role of Paxillin in PCa.

PMID- 29581776
TI  - Association of Smoking and XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2, and MMP9 Gene
      Polymorphisms with the early detection and occurrence of Laryngeal Squamous
      Carcinoma.
AB  - A total of 200 smoking-related laryngeal carcinoma patients with pathology
      confirmation from the Eye and ENT Hospital and 190 high-risk smokers were
      included in a survey. All of the participants had a smoking index greater than
      400 (cigarettes/day*year.) We obtained data on clinical and baseline
      characteristics, and peripheral blood was obtained and subjected to DNA
      extraction to analyse the correlation between smoking and the occurrence of
      laryngeal carcinoma. We selected candidate genes and SNP fragments that were
      found to be closely associated with smoking-related tumours in preliminary
      studies. The selected candidate genes were XPG, CYP1A1, OGG1, ERCC5, ERCC1, MMP2,
      and MMP9. We then performed SNP sequencing using Sequenom SNP detection
      technology. Target genes and single nucleotide polymorphism (SNP) fragments were
      evaluated to analyse the correlation between genotype or allele and smoking
      related laryngeal carcinoma and to identify susceptibility genes related to
      laryngeal carcinoma. The results included four main findings: (1) The smoking
      index differed significantly between laryngeal cancer patients and control
      subjects (P=0.0035). The risk of laryngeal cancer was increased among individuals
      with a smoking index greater than 600 cigarettes/day*year (P=0.03). (2) The
      smoking index was significantly correlated with the T, N and clinical stages
      (P<0.05). (3) The polymorphisms CYP1A1-rs1048943, rs4646421, and rs4646422 and
      MMP9-rs17577 were significantly associated with laryngeal squamous carcinoma
      (P<0.05). (4) After stratifying the subjects by smoking degree, the GT genotype
      of ERCC1-rs2298881 was associated with a significantly greater risk of laryngeal
      carcinoma among heavy smokers (P=0.04). The results suggest that smoking plays an
      important role in the occurrence and development of laryngeal squamous carcinoma;
      CYP1A1 and MMP9 might be susceptibility gene SNPs for smoking-related laryngeal
      carcinoma, and ERCC1 might play an important role in heavy smokers. The results
      of this study might help identify an early marker for the detection and
      prevention of laryngeal carcinoma.

PMID- 29581777
TI  - Prospective matched study on comparison of volumetric-modulated arc therapy and
      intensity-modulated radiotherapy for nasopharyngeal carcinoma: dosimetry,
      delivery efficiency and outcomes.
AB  - Background: The purpose of this study is to assess the feasibility of volumetric
      modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients by
      comparing the physical dosimetry, delivery efficiency and clinical outcomes with
      intensity-modulated radiotherapy (IMRT). Methods: A prospective matched study was
      performed for patients with newly diagnosed NPC who underwent VMAT or IMRT. The
      patients in two groups were equally matched in terms of gender, age, tumor stage
      and chemotherapy. The target coverage, homogeneity index (HI) and conformity
      index (CI) of the planning target volume (PTV), organs at risk (OARs) sparing,
      average treatment time and clinical outcomes were analyzed. Results: From June
      2013 to August 2015, a total of 80 patients were enrolled in this study, with 40
      patients in each group. The coverage of PTV was similar for both groups. D2 was
      observed slight difference only in early stage disease (T1-2) (VMAT vs. IMRT,
      7494+/-109 cGy vs. 7564+/-92 cGy; p=0.06). The HI of VMAT group was better than
      that of IMRT group (p=0.001), whereas CI was slightly worse (p=0.061). The
      maximum doses received by the brain stem, spinal cord, and optic nerve of VMAT
      were higher than those of IMRT (p<0.05). But the irradiation volumes in healthy
      tissue were generally lower for VMAT group, with significant differences in V20,
      V25 and V45 (p<0.05). With regard to the delivery efficiency compared with IMRT
      (1160 +/- 204s), a 69% reduction in treatment time was achieved by VMAT (363 +/-
      162s). Both groups had 5 cases of nasopharyngeal residual lesions after
      radiotherapy. The 2-year estimated local relapse-free survival, regional relapse
      free survival and locoregional relapse-free survival, distant metastasis-free
      survival, disease-free survival and overall survival were similar between two
      groups, with the corresponding rates of 100%, 97.4%, 97.4%, 90.0%, 90.0% and
      92.4% in VMAT group, and 100%, 100%, 100%, 95.0%, 95.0% and 97.5% in IMRT group,
      respectively. Conclusions: Both VMAT and IMRT can meet the clinical requirements
      for the treatment of NPC. The short-term tumor regression rates and 2-year
      survival rates with the two techniques are comparable. The faster treatment time
      benefits of VMAT will enable more patients to receive precision radiotherapy.

PMID- 29581778
TI  - The anti-tumor effects of dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase
      inhibitor Trichostatin A on inducing autophagy in esophageal squamous cell
      carcinoma.
AB  - The effect and regulation of autophagy-related proteins Beclin-1 and LC3 in
      esophageal squamous cell carcinoma have not been fully studied. The aim of this
      study was to assess the expression of Beclin-1 and LC3 in ESCCs, and to
      investigate the association between the two markers and clinicopathological
      characteristics as well as prognosis. Meanwhile, we explored the anti-tumor
      effect of the PI3K/mTOR dual inhibitor BEZ235 and the histone deacetylase
      inhibitor TSA on inducing autophagy in ESCC cells. Our study included 118 ESCC
      tumors and paired non-tumor esophageal mucosa tissues. Beclin-1 and LC3
      expression were performed by immunohistochemistry. Human ESCC cells Eca-109 and
      TE-1 were treated with BEZ235 and TSA either alone or in combination in Vitro.
      The expression of both Beclin-1 and LC3 proteins were decreased significantly in
      ESCCs, but there was no significant relation between the expression of Beclin-1
      and LC3 (P = 0.427). The negative expression of either Beclin-1 or LC3 was
      associated with advanced TNM stages (P = 0.006 and P<0.001, respectively).
      Patients with a high expression of Beclin-1 and LC3 predict better prognosis. In
      Vitro co-treatment with BEZ235 and TSA showed a synergistic effect on inhibition
      of ESCC cell viability and induction of autophagy with the increasing expressions
      of Beclin-1, LC3-II and the ratio of LC3-II/LC3-I. Our results demonstrated that
      the autophagy-related proteins Beclin-1 and LC3 were decreased in ESCCs and the
      low expression of the two markers predicted a worse prognosis. The co-treatment
      of BEZ235 and TSA significantly induced autophagy and enhanced anti-tumor
      activities, provided a new effective therapeutic target in ESCCs.

PMID- 29581779
TI  - IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma.
AB  - Background. Recent studies have shown that isocitrate dehydrogenase 1/2 (IDH1/2)-
      activating mutations occur in a variety of cancers, including acute myeloid
      leukaemia, gliomas, and chondrosarcomas (CHS)s. The effect of IDH1/2 mutation on
      overall survival (OS) has not been reported in CHS. The aim of our study was to
      assess the prevalence of known cancer-related gene mutations in CHS, as well as
      their prognostic role in patient survival. Methods. DNA from FFPE samples of 80
      patients (F:M- 1:1.3; mean age: 58 years; range 27-86) with histologically
      confirmed CHS (G1:29; G2:34; G3:17) was subjected to library preparation with the
      Ion AmpliSeq Cancer Hotspot Panel v2 and sequenced on the PGM Ion Torrent.
      Results. Among the clinical features only histological grade influenced OS. Deep
      sequencing identified 1784 single nucleotide variants. Of them, 426 were
      considered to be pathogenic or probably pathogenic. Activating IDH1/2 mutations
      were found in 27 patients (34%) including 17 R132 IDH1 (21%), 10 R172 IDH2 (13%)
      and 3 R140 IDH2 variants (4%). Three patients had concurrent IDH1 and IDH2
      mutations. The R140 IDH2 mutant has not been reported to date in CHS patients. OS
      for CHS patients with IDH1/2 mutations was significantly lower than in patients
      without mutations (93% vs 64%; p<0.001). No other genetic feature of the Cancer
      Hotspot Panel had an impact on OS. Conclusions. In CHS, IDH1/2-mutation status
      and the histological aggressiveness of the CHS are important predictors for OS.
      The R140 IDH2 may also be a novel target for the treatment of CHS patients.

PMID- 29581780
TI  - Switch of the ovarian cancer cell to a calcifying phenotype in the calcification
      of ovarian cancer.
AB  - OBJECTIVE: The main aim of this study was to study swith of the ovarian cancer
      cell to a calcifying phenotype in the formation of calcification in ovarian
      cancer, and to offer some help for ovarian cancer's diagnosis and differentiation
      therapy. METHODS: The mineralization of ovarian cancer cell lines SKOV3 was
      induced via calcification medium for 21 d in vitro. Alizarin red staining, von
      kossa staining, calcein fluorescence staining and ALP activity detection were
      used to identify mineralization in calcification model of ovarian cancer. Also,
      the changes of ultrastructure and the mineralization biomarkers after the
      induction of calcification medium were investigated by transmission electron
      microscopy and western blot, respectively. The SKOV3 cells migration behavior
      after the induction of calcification medium was evaluated by using transwell
      assay and scratch wound. Finally, mineralization biomarkers were verified in 40
      cases of calcified ovarian cancer specimens and matched 40 non-calcified ovarian
      cancer tissues. RESULTS: Classical calcium salt detection methods confirmed that
      the culture of SKOV3 cells in calcification medium was an appropriate ovarian
      cancer calcification model in vitro. Transmission electron microscopy and western
      blot revealed respectively the presence of cells with morphological
      characteristics of osteoblasts and the upregulation of mineralization biomarkers
      expression in treatment group. Transwell assay and scratch wound showed the
      decreased SKOV3 cell migration in treatment group. In specimens, the
      calcification occurred predominantly in well-differentiated carcinomas and the
      expression of the BMP2 and OPN elevated in calcified group. CONCLUSION: Our study
      showed that the switch of the ovarian cancer cell to a calcifying phenotype in
      the formation of calcification in ovarian cancer. The calcified phenotypic
      transformation may inform the new prospective in ovarian cancer therapy.

PMID- 29581781
TI  - LASS2 regulates invasion and chemoresistance via ERK/Drp1 modulated mitochondrial
      dynamics in bladder cancer cells.
AB  - Mitochondria coordinated a lot of vital cellular processes of energy production
      and distribution. Change of mitochondrial functions has been implicated in cancer
      progression. The present study aims to investigate the involvement of
      mitochondria dynamics in LASS2 induced invasion and chemoresistance of bladder
      cancer cells. J82 and BIU87 cell lines were used for LASS2 plasmid transfection
      while siRNA knockdown was carried out in 5637 cell line. Matrigel invasion assay
      and Annexin V/PI staining demonstrated that LASS2 negatively regulated cancer
      cell invasion and chemoresistance. JC-1 staining suggested that LASS2
      overexpression downregulated mitochondrial membrane potential. Mitotracker
      staining showed that LASS2 induced mitochondrial fusion and inhibited
      mitochondrial fission. In addition, LASS2 overexpression downregulated expression
      of mitochondrial fission protein p-Drp1 Drp1 and Fis1. While depletion of LASS2
      exhibited the opposite effects. Drp1 inhibitor Mdivi abolished invasion and
      chemoresistance induced by LASS2 siRNA. Furthermore, we found that LASS2
      overexpression could inhibit phosphorylation of ERK, which act upstream of Drp1.
      ERK inhibitor PD98059 suppressed Drp1 phosphorylation and abrogated the effects
      of LASS2 depletion. In conclusion, the present study demonstrated that LASS2
      inhibits bladder cancer invasion and chemoresistance through regulation of ERK
      Drp1 induced mitochondrial dynamics.

PMID- 29581782
TI  - A Novel Risk prediction Model for Patients with Combined Hepatocellular
      Cholangiocarcinoma.
AB  - Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse
      outcomes or misuse of clinical therapies, an increasing number of patients have
      undergone liver transplantation, transcatheter arterial chemoembolization (TACE)
      or other treatments. Objective: To construct a convenient and reliable risk
      prediction model for identifying high-risk individuals with combined
      hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent
      surgical resection for liver cancer at Zhongshan Hospital were enrolled in this
      study. The epidemiological and clinical characteristics of the patients were
      collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate
      analyses) were evaluated using backward stepwise method. A receiver operating
      characteristic (ROC) curve was used to assess model discrimination. Calibration
      was performed using the Hosmer-Lemeshow test and a calibration curve. Internal
      validation was performed using a bootstrapping approach. Results: Among the
      entire study population, 250 patients (7.42%) were pathologically defined with
      CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and
      portal vein tumor thrombus (PVTT) were included in the final risk prediction
      model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77).
      Bootstrapping validation presented negligible optimism. When the risk threshold
      of the prediction model was set at 20%, 2.73% of the patients diagnosed with
      liver cancer would be diagnosed definitely, which could identify CHC patients
      with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of
      33.70%. Conclusions: Herein, the study established a risk prediction model which
      incorporates the clinical risk predictors and CT/MRI-presented PVTT status that
      could be adopted to facilitate the diagnosis of CHC patients preoperatively.

PMID- 29581783
TI  - Effect of the oncolytic ECHO-7 virus Rigvir(r) on the viability of cell lines of
      human origin in vitro.
AB  - Background: The role of oncolytic viruses in cancer treatment is increasingly
      studied. The first oncolytic virus (Rigvir(r), ECHO-7) was registered in Latvia
      over a decade ago. In a recent retrospective study Rigvir(r) decreased mortality
      4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study
      are to test the effect of Rigvir(r) on cell line viability in vitro and to
      visualize the cellular presence of Rigvir(r) by immunocytochemistry. Methods: The
      cytolytic effect of Rigvir(r) on the viability of FM-9, RD, AGS, A549, HDFa, HPAF
      II, MSC, MCF7, HaCaT, and Sk-Mel-28 cell lines was measured using live cell
      imaging. PBMC viability was measured using flow cytometry. The presence of ECHO-7
      virus was visualized using immunocytochemistry. Statistical difference between
      treatment groups was calculated using two-way ANOVA. Results: Rigvir(r) (10%,
      volume/volume) reduced cell viability in FM-9, RD, AGS, A549, HDFa, HPAF-II and
      MSC cell lines by 67-100%. HaCaT cell viability was partly affected while
      Rigvir(r) had no effect on MCF7, Sk-Mel-28 and PBMC viability. Detection of ECHO
      7 by immunocytochemistry in FM-9, RD, AGS, A549, HDFa, HPAF-II and Sk-Mel-28 cell
      lines suggests that the presence of Rigvir(r) in the cells preceded or coincided
      with the time of reduction of cell viability. Rigvir(r) (10%) had no effect on
      live PBMC count. Conclusions: The results suggest that Rigvir(r) in vitro reduces
      the viability of cells of human melanoma, rhabdomyosarcoma, gastric
      adenocarcinoma, lung carcinoma, pancreas adenocarcinoma but not in PBMC. The
      presence of Rigvir(r) in the sensitive cells was confirmed using anti-ECHO-7
      antibodies. The present results suggest that a mechanism of action for the
      clinical benefit of Rigvir(r) is its cytolytic properties. The present results
      suggest that the effect of Rigvir(r) could be tested in other cancers besides
      melanoma. Further studies of possible Rigvir(r) entry receptors are needed.

PMID- 29581784
TI  - Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma
      Treated with Fasudil.
AB  - Fasudil has been proven to be a promising chemotherapeutic drug for various
      malignancies. However, the potential anticancer effects of fasudil in oesophageal
      squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA
      activity is inhibited by fasudil in ESCC cells. Then measured the effects of
      fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both
      induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was
      inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and
      pharmacologic agent (chloroquine) treatment, both treatments also significantly
      sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro.
      Our study showed autophagy inhibitors combined with fasudil could significantly
      induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.

PMID- 29581785
TI  - A Meta-Analysis: Methylenetetrahydrofolate Reductase C677T Polymorphism in
      Gastric Cancer Patients Treated with 5-Fu Based Chemotherapy Predicts Serious
      Hematologic Toxicity but Not Prognosis.
AB  - 5-fluorouracil (5-Fu) metabolism associated enzyme, methylenetetrahydrofolate
      reductase (MTHFR)'s polymorphism C677T can affect enzyme activity and a series of
      studies have been performed to examine the association of this MTHFR polymorphism
      with the clinical outcomes of gastric cancer (GC) patients treated with 5-Fu
      based chemotherapies. However, the results are inconsistent and inconclusive.
      Therefore, a more comprehensive summary like meta-analysis on this topic is
      needed. We performed a systematic literature search of PubMed and Embase up to
      May 20, 2017. Researches exploring MTHFR polymorphisms C677T's relationship with
      the clinical outcomes (response rate, overall survival and toxicity) of GC
      patients treated with 5-Fu based chemotherapy were included. The association was
      measured by odds ratios (ORs) or hazard ratios (HRs) combined with their 95%
      confidence intervals (CIs) using random/fixed effects model according to the
      studies' heterogeneity. Subgroup, sensitivity and publication bias analyses were
      conducted. Thirteen studies were finally included in this meta-analysis. No
      significant association was found between response rate [TT/ (CC+CT) OR=1.31, 95%
      CI: 0.62-2.76] or overall survival [(CT+TT)/CC HR=1.05, 95% CI: 0.86-1.26;
      TT/(CT+CC) HR=1.48, 95% CI: 0.53-4.15] and MTHFR polymorphism C677T. However, GC
      patients with CC or CT genotype tended to experience less severe hematologic
      toxicity than those with TT genotype [(CC+CT)/TT OR=0.66, 95% CI: 0.48-0.91]. In
      conclusion, MTHFR C677T polymorphism predicts severe hematologic toxicity in GC
      patients receiving 5-Fu based chemotherapy, but not the efficiency.

PMID- 29581786
TI  - Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and
      disease-free survival in locally advanced rectal cancer patients receiving
      preoperative chemoradiotherapy and radical surgery.
AB  - Objective: Although preoperative chemoradiotherapy (CRT) followed by total
      mesorectal excision (TME) is the standard treatment for locally advanced rectal
      cancer (LARC), the clinical efficacy differs among patients. This study was
      conducted to determine the association between genetic variations in the
      PI3K/PTEN/AKT/mTOR pathway and clinical outcomes in LARC patients. Methods:
      Sixteen tagging single-nucleotide polymorphisms (SNPs) in five core genes
      (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) were genotyped. The associations of these
      SNPs with tumor response to preoperative CRT, postoperative disease-free survival
      (DFS) and overall survival (OS) were identified. Crude odds ratios (ORs) and
      hazard ratios (HRs) were adjusted by age, sex, clinical stage, tumor
      differentiation, tumor location, cycles of preoperative chemotherapy and time
      interval from CRT completion to surgery. Results: In an analysis of 97 LARC
      patients, the G/T+G/G genotype of AKT1:rs2498804 was associated with an increased
      tumor response rate (adjusted OR = 2.909, 95% confidence interval (CI), 1.127
      7.505, P = 0.027). At a median of 65.7 months of follow-up, the G/C+C/C genotype
      of AKT2:rs8100018 was associated with a reduced risk of postoperative recurrence
      (adjusted HR = 0.414; 95% CI, 0.187-0.914, P = 0.029). Patients carrying the
      G/C+C/C genotype in AKT2:rs8100018 presented a higher 5-year DFS rate than those
      with the wild-type genotype (79.2% vs. 62.3%, P = 0.038). None of the SNPs were
      significantly associated with pathological complete response (pCR) or 5-year OS.
      Conclusions: The current study indicates that genetic variations within the PI3K/
      PTEN/AKT/mTOR signaling pathway are associated with the clinical outcomes of LARC
      patients undergoing preoperative CRT followed by radical surgery.

PMID- 29581787
TI  - SULT1E1 inhibits cell proliferation and invasion by activating PPARgamma in
      breast cancer.
AB  - Sulfotransferase family 1E member 1 (SULT1E1) is known to catalyze
      sulfoconjugation and play a crucial role in the deactivation of estrogen
      homeostasis, which is involved in tumorigenesis and the progression of breast and
      endometrial cancers. Our previous study has shown that the protein levels of
      SULT1E1 were decreased in breast cancer; however, the underlying mechanism is
      still poorly understood. In this study, we explored the functional and molecular
      mechanisms by which SULT1E1 influenced breast cancer. Here, we identified that
      overexpression of SULT1E1 inhibited breast cancer cell growth through inducing
      apoptosis and arresting cell cycle progression. Furthermore, enforced expression
      of SULT1E1 suppressed tumor cell migration and invasion. Moreover, we found that
      the activation of PPARgamma was required for SULT1E1-mediated downregulation of C
      myc, Cyclin D1, MMP-2 and MMP-9 as well as for cell apoptosis, migration and
      invasion. In addition, the overexpression of SULT1E1 significantly inhibited
      tumor growth in vivo. Taken together, our findings indicated that SULT1E1
      performed its tumor suppressor characteristics by activating PPARgamma, which
      provided a novel target for patients with breast cancer.

PMID- 29581788
TI  - Increased HE4 mRNA Expression Correlates with High Level Of eIF3a mRNA And Better
      Survival in Women with Epithelial Ovarian Cancer.
AB  - Human epididymis protein 4 (HE4) is one of the most promising biomarkers for
      epithelial ovarian cancer (EOC). The majority of previous studies utilized the
      serum level or tissue protein expression of HE4 based upon immunohistochemistry
      (IHC) to evaluate the role of HE4 in the diagnosis, prognosis, and surveillance
      of EOC, but very little is known about HE4 mRNA expression. Eukaryotic
      translation initiation factor 3a (eIF3a) is implicated in oncogenesis and has
      been investigated extensively as a potential biomarker for malignancy. We
      previously reported a positive correlation between IHC expressions of eIF3a and
      HE4 in EOC. In the present study, we performed RT-PCR to determine mRNA
      expressions of HE4 and eIF3a in 30 normal ovarian tissues, 45 benign, 20
      borderline and 94 malignant ovarian tumors. The association of HE4 and eIF3a mRNA
      expressions with clinicopathological characteristics and patient survivals was
      investigated. IHC was also performed in the same participants to investigate the
      correlation between mRNA and protein levels of HE4. HE4 mRNA level was found to
      be 48.42 +/- 74.55 (mean +/- SD, range: 0.01-343.99), significantly higher in
      primary EOC than in the borderline tumor, benign tumor, and normal ovarian tissue
      (P<0.001). The cutoff value was 13.99 for HE4 to discriminate malignant from
      benign tumors at 68.1% sensitivity and 93.0% specificity. By Spearman's
      correlation test, HE4 mRNA expression was indicated to positively correlate with
      serum CA125 level (r=0.530, P<0.001). Higher HE4 mRNA expression was associated
      with decreased frequency of lymph node metastasis (P=0.038) and better overall
      survival (OS) (P=0.007) in primary EOC. Multivariable analysis showed an
      independent prognostic value of the relative mRNA level of HE4 greater than one
      for OS (Hazard Ratio, 0.069, 95%CI, 0.009-0.530, P=0.010). eIF3a mRNA expression
      in women with primary EOC was 0.95 +/- 1.19 (mean +/- SD, range: 0.06-7.46),
      which was in a positive linear correlation with HE4 mRNA expression (r=0.310,
      P=0.002). In the present study, the HE4 mRNA level was unparalleled with IHC
      expression of HE4 (P>0.05). Collectively, our study revealed that increased HE4
      mRNA expression correlates with high level of eIF3a mRNA and better survival in
      women with EOC, which calls for further investigations.

PMID- 29581790
TI  - Surgical Treatment of Combined Hepatocellular-Cholangiocarcinoma is as Effective
      in Elderly Patients as it is in Younger Patients: A Propensity Score Matching
      Analysis.
AB  - Aims: To compare the long-term prognosis of younger and elderly patients with
      combined hepatocellular-cholangiocarcinoma (CHC) who underwent curative resection
      between 1993 and 2014 at our center. Methods: Two hundred and thirteen patients
      who underwent liver resection for CHC were enrolled in our study. The overall
      survival (OS) and disease-free survival (DFS) of elderly patients (age>=60, n=52)
      and younger patients (age<60, n=161) were compared by multivariate analysis and
      propensity score matching (PSM) analysis. Results: Among the 213 CHC patients,
      the elderly patients had a higher rate of worse Child-Pugh grade (P=0.027),
      abnormal serum albumin (P<0.001) and lymphoid metastases (P=0.024). The
      proportion of HBV-positive CHC patients (74.6%, 159/213) was much higher than
      that observed in healthy cohorts. Younger patients had a higher rate of hepatitis
      B virus (HBV) infection compared to older patients (83.9% vs 46.2%, P<0.001). OS
      and DFS of the elderly and younger patients before and after propensity score
      matching were comparable. Conclusion: Elderly and younger patients who underwent
      liver resection for CHC have comparable long-term OS and DFS.

PMID- 29581789
TI  - Integrated Oncogenomic Profiling of Copy Numbers and Gene Expression in Lung
      Adenocarcinomas without EGFR Mutations or ALK Fusion.
AB  - Targeted therapies based on EGFR mutations or on the ALK fusion oncogene have
      become the standard treatment for certain patients with lung adenocarcinoma
      (LUAD). However, most LUAD patients have no EGFR mutation or ALK fusion, and
      their oncogenetic alterations remain to be characterized. Here we conducted an
      integrated analysis of public datasets to assess the genomic alterations of 23
      highly lung cancer-associated genes. The copy numbers of these genes were
      measured in ten micro-dissected, paired tumors and normal lung tissues of LUAD
      patients without EGFR mutations or ALK fusion. The copy numbers of PTEN, RB1,
      HMGA2, and PTPRD were lower in tumors compared with those for normal tissues.
      Although there were reduced mRNA levels of PTEN and RB1 in tumors, there was a
      correlation between copy number and expression only for PTEN. In addition,
      analysis of the copy number alterations of these 23 genes revealed correlations
      between EMSY/CCND1, EMSY/PIK3CA, CCND1/CDKN2A, and CCND1/PIK3CA. Our exploration
      of integrated copy number and gene expression analysis gives priority to the PTEN
      PIK3CA and RB1-CCND1 pathways in developing therapeutic strategies for LUAD
      patients without EGFR mutations or ALK fusion.

PMID- 29581791
TI  - Usefulness of Bronchoscopic Rebiopsy of Non-Small Cell Lung Cancer with Acquired
      Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor.
AB  - Background: Approximately 50% of non-small cell lung cancer (NSCLC) patients with
      acquired resistance to EGFR-TKI harbor the EGFR mutation T790M. The recent
      development and wide use of third-generation EGFR-TKIs targeting T790M-mutant
      NSCLCs have increased the importance of rebiopsy after EGFR-TKI failure. We aimed
      to investigate the advantages of flexible bronchoscopy as a rebiopsy method and
      the prevalence of and factors affecting the T790M mutation after EGFR-TKI
      failure. Methods: We investigated 139 patients who had undergone bronchoscopic
      rebiopsy and endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) between Sep 2014 and Jul 2016. Results: Among the 139 patients,
      bronchoscopic rebiopsy yielded successful pathological diagnoses in 102 (73.4%).
      Among them, 41 patients with EGFR-mutant lung adenocarcinoma and EGFR-TKI
      progression were selected for an investigation of T790M mutation prevalence at
      rebiopsy. The initial EGFR mutations were exon 19 del (56.1%), L858R or L861Q
      (34.1%), and others (9.8%). The most common rebiopsy method was transbronchial
      lung biopsy (41.5%), followed by EBUS-TBNA (26.8%) and endobronchial biopsy
      (19.5%). The median interval to T790M emergence was the longest among cases with
      exon 19 deletion (14.1 months), followed by exon 21 L858R or L861Q (11.3 months)
      and other rare EGFR mutations (2.9 months). The T790M mutation was identified in
      18 (43.9%) patients, and exon 19 del was the most significant factor affecting
      T790M mutation development (hazard ratio: 6.875, P = 0.014). Conclusions:
      Bronchoscopy was more useful than other rebiopsy approaches. The T790M emergence
      rate was highest in cases with exon 19 deletion, likely as a consequence of long
      term EGFR-TKI exposure.

PMID- 29581792
TI  - Inhaled Immunotherapy Administration for Lung Cancer; Efficient? Certainly
      Possible.
AB  - Lung cancer is still diagnosed at a late stage in most lung cancer patients.
      Regarding Non-small Cell lung cancer there are novel therapies such as; tyrosine
      kinase inhibitors and immunotherapy. Currently we have two immunotherapies that
      can be used either as first-line treatment or second line treatment;
      pembrolizumab and nivolumab. A third one is being investigated as a combination
      of immunotherapy; ipilimumab. Aerosol treatment has been investigated for many
      diseases not only for the lung, but also for systematic diseases. The design of
      cups was found the most significant factor in producing significant effects. The
      comparison of cups reveals the design J as the most capable of reducing the
      droplets at a minimum size of mass median aerodynamic diameter (MMAD) MMAD=1.99.
      Drug effect comes second in sequence (F=62.04) showing that nivolumab is the most
      drastic preparation at low particle sizes (1.89), two drugs share an intermediate
      particle diameter (pembrolizumab and ipilimumab). In total drugs demonstrate a
      decreasing droplet size: Ipilimumab>Pembrolizumab> Nivolumab.

PMID- 29581793
TI  - Neonatal exposure to hyperoxia leads to persistent disturbances in pulmonary
      histone signatures associated with NOS3 and STAT3 in a mouse model.
AB  - Background: Early pulmonary oxygen exposure is one of the most important factors
      implicated in the development of bronchopulmonary dysplasia (BPD). Methods: Here,
      we analyzed short- and long-term effects of neonatal hyperoxia on NOS3 and STAT3
      expression and corresponding epigenetic signatures using a hyperoxia-based mouse
      model of BPD. Results: Early hyperoxia exposure led to a significant increase in
      NOS3 (median fold change * 2.37, IQR 1.54-3.68) and STAT3 (median fold change *
      2.83, IQR 2.21-3.88) mRNA levels in pulmonary endothelial cells with
      corresponding changes in histone modification patterns such as H2aZac and H3K9ac
      hyperacetylation at the respective gene loci. No complete restoration in histone
      signatures at these loci was observed, and responsivity to later hyperoxia was
      altered in mouse lungs. In vitro, histone signatures in human aortic endothelial
      cells (HAEC) remained altered for several weeks after an initial long-term
      exposure to trichostatin A. This was associated with a substantial increase in
      baseline eNOS (median 27.2, IQR 22.3-35.6) and STAT3alpha (median 5.8, IQR 4.8
      7.3) mRNA levels with a subsequent significant reduction in eNOS expression upon
      exposure to hypoxia. Conclusions: Early hyperoxia induced permanent changes in
      histones signatures at the NOS3 and STAT3 gene locus might partly explain the
      altered vascular response patterns in children with BPD.

PMID- 29581794
TI  - Noninvasive Glioblastoma Testing: Multimodal Approach to Monitoring and
      Predicting Treatment Response.
AB  - Glioblastoma is the most aggressive adult primary brain tumor which is incurable
      despite intensive multimodal treatment. Inter- and intratumoral heterogeneity
      poses one of the biggest barriers in the diagnosis and treatment of glioblastoma,
      causing differences in treatment response and outcome. Noninvasive prognostic and
      predictive tests are highly needed to complement the current armamentarium.
      Noninvasive testing of glioblastoma uses multiple techniques that can capture the
      heterogeneity of glioblastoma. This set of diagnostic approaches comprises
      advanced MRI techniques, nuclear imaging, liquid biopsy, and new integrated
      approaches including radiogenomics and radiomics. New treatment options such as
      agents targeted at driver oncogenes and immunotherapy are currently being
      developed, but benefit for glioblastoma patients still has to be demonstrated.
      Understanding and unraveling tumor heterogeneity and microenvironment can help to
      create a treatment regime that is patient-tailored to these specific tumor
      characteristics. Improved noninvasive tests are crucial to this success. This
      review discusses multiple diagnostic approaches and their effect on predicting
      and monitoring treatment response in glioblastoma.

PMID- 29581795
TI  - The Association of Digit Ratio (2D : 4D) with Cancer: A Systematic Review and
      Meta-Analysis.
AB  - Objective: Intrauterine sex hormone environment as indicated by the second to the
      fourth digit ratio (2D : 4D) can be associated with cancer risk. This systematic
      review and meta-analysis aimed to evaluate the association of 2D : 4D with cancer
      diagnosis, malignancy, and age at presentation. Methods: Studies that evaluated
      the association of 2D : 4D with cancer risk were collected from Pubmed/MEDLINE
      and Clarivate Analytics databases. Nineteen studies were included in the
      qualitative analysis. Results: The 2D : 4D ratio was studied in prostate cancer,
      breast cancer, testicular cancer, gastric cancer, oral cancer, brain tumors, and
      cervical intraepithelial neoplasia. Low 2D : 4D was associated with prostate
      cancer, gastric cancer, and brain tumors, while high 2D : 4D, with breast cancer
      risk and cervical dysplasia. The 2D : 4D ratio was not associated with prostate,
      breast, and gastric cancer stage. Greater 2D : 4D ratio was associated with
      younger presentation of breast cancer and brain tumors. The meta-analyses
      demonstrated that testicular cancer was not associated with right-hand 2D : 4D
      ratio (p = 0.74) and gastric cancer was not associated with right-hand (p = 0.15)
      and left-hand (p = 0.95) 2D : 4D ratio. Conclusions: Sex hormone environment
      during early development is associated with cancer risk later in life. Further
      studies exploring the link between intrauterine hormone environment and cancer
      risk are encouraged.

PMID- 29581796
TI  - Polymorphisms in Vitamin D Receptor Genes in Association with Childhood Autism
      Spectrum Disorder.
AB  - Both genetic and environmental factors have been implicated in the etiology of
      autism spectrum disorder (ASD). This case-control study aimed to determine the
      association of single-nucleotide polymorphisms (SNPs) rs731276 (TaqI), rs1568820
      (Cdx2), rs1544410 (BsmI), and rs2228570 (FokI) in the vitamin D receptor (VDR)
      gene with susceptibility of childhood ASD and severity of the disease. A total of
      201 children with ASD and 200 healthy controls from the Han Chinese population
      were recruited. SNP genotyping was carried out by TaqMan probe-based real-time
      PCR using genomic DNA extracted from blood cells. Among four examined SNPs, only
      the CT genotype (odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.05
      3.68, P = 0.0351) and the C allele (OR = 1.88, 95% CI = 1.02-3.46, P = 0.0416) of
      the rs731276 were significantly associated with increased risks of childhood ASD.
      None of the SNPs were associated with severity of childhood ASD. Our results
      reveal that certain polymorphisms in the VDR gene are a risk factor related to
      childhood ASD in the Han Chinese population.

PMID- 29581797
TI  - Exercise Therapy for Patients With Type 2 Diabetes: A Narrative Review.
AB  - To achieve excellent glycemic control in patients with type 2 diabetes, an
      adequate prescription of exercise therapy is required. The meta-analyses proposed
      that high-intensity training improves metabolic parameters in patients with pre
      diabetes or type 2 diabetes and low physical activity is associated with an
      increased risk of incident type 2 diabetes. Here, we would introduce literatures
      about effects of physical activity on mortality, cardiovascular events, and
      metabolic parameters, to encourage understanding of exercise therapy, and then
      describe how to prescribe exercise therapy for patients with type 2 diabetes. We
      also show the usefulness of non-exercise activity thermogenesis for diabetic
      patients who cannot perform volitional sporting-like exercise because of diabetic
      complication and/or comorbidity, by presenting results of our previous studies.

PMID- 29581798
TI  - The Main Anatomical Variations of the Pancreatic Duct System: Review of the
      Literature and Its Importance in Surgical Practice.
AB  - Anatomical variations or anomalies of the pancreatic ducts are important in the
      planning and performance of endoscopic retrograde cholangiopancreatography (ERCP)
      and surgical procedures of the pancreas. Normal pancreatic duct anatomy occurs in
      approximately 94.3% of cases, and multiple variations have been described for the
      remaining 5.7%. The purpose of this study was to review the literature on the
      pancreatic duct anatomy and to underline its importance in daily invasive
      endoscopic and surgical practice. Two main databases were searched for suitable
      articles published from 2000 to 2017, and results concerning more than 8,200
      patients were included in the review. The most common anatomical variation was
      that of pancreas divisum, which appeared in approximately 4.5% of cases.

PMID- 29581799
TI  - The Impact of the Underlying Risk in Control Group and Effect Measures in Non
      Inferiority Trials With Time-to-Event Data: A Simulation Study.
AB  - Background: We designed a simulation study to assess how the conclusions of a non
      inferiority trial (NIT) will change if the observed risk is different from the
      expected risk. Methods: We simulated Weibull distribution time-to-event data with
      a true hazard ratio (HR) being equal or close to 1. The empirical margins and
      sample size of a hypothetical trial were chosen based on a systematic review.
      Setting the significance level at 5% for the two-sided confidence interval (CI),
      we examined the statistical power (i.e., the probabilities of the upper limit of
      the 95% CI falling within the margin) of using two measures at various underlying
      risk in the control group. Results: Using the empirical margins, HRs of 1.2, 1.35
      or 1.5, the statistical power is lower than 0.22 when the underlying risk in the
      control group is less than 10%, but the power increases along with the higher
      underlying risk. The predicted upper limit of the 95% CI of the difference in two
      Kaplan-Meier estimators (DTKME) is low when risk is low (< 20%) or high (> 80%),
      but reaches the highest value when risk is around 50%. When the underlying risk
      in the control group is lower than 10%, measures of DTKME resulted in much higher
      power than HR. Conclusions: When HR is the effect measure, the probability of
      concluding non-inferiority will increase as the underlying risk in the control
      group increases. When DTKME is the effect measure, the probability of concluding
      non-inferiority will decrease as the underlying risk in the control increases. In
      this case, the probability of concluding non-inferiority is at a minimum when the
      control risk reaches about 50%. When the risk in the control arm is less than
      10%, the conclusion of an NIT is sensitive to the choice of effect measure.

PMID- 29581800
TI  - Impact of Drug Induced Long QT Syndrome: A Systematic Review.
AB  - Background: Drug induced long QT syndrome is quite common in daily clinical
      practice but its impact is unknown. Methods: PubMed and EMBASE databases (until
      May 2, 2017) were searched to identify studies reporting drug induced long QT
      syndrome and followed the PRISMA guidelines. The main outcomes measured in these
      studies were QTc prolongation, ventricular arrhythmias, torsade de pointes (TdP)
      and death. Results: Out of 176 non-duplicate reports, 36 studies satisfied
      inclusion criteria and provided data on patients exposed to drugs that can
      potentially cause long QT. Totally, 14,756 patients were exposed and 930 patients
      (6.3%) were found to have QTc prolongation. The number of males was 6,400 and
      females were 5,723 patients. The mean age of the patients was 43.8 +/- 9.36
      years. Ventricular arrhythmias were found in 379 patients (2.6%), 26 patients
      were found to have premature atrial contractions (PACs) and premature ventricular
      contractions (PVCs). TdP was found in 49 patients (0.33 %), sudden cardiac death
      (SCD) was found in five patients and 586 patients were found to have all-cause
      mortality. Conclusions: Around 6% of patients have risk of QT prolongation when
      exposed but only 0.3% developed TdP and 2.6% developed ventricular arrhythmias.
      Risk of developing arrhythmias is higher with concomitant use of multiple QT
      prolonging drugs.

PMID- 29581801
TI  - Sidestream Dark Field Imaging of the Microcirculation to Assess Preeclampsia
      Microvascular Dysfunction.
AB  - Background: Development of predictive models of preeclampsia has only yielded
      modest results. We hypothesized that impaired indices of microcirculatory
      function could be detected using sidestream dark field imaging. The objective of
      this study was to examine microvascular function in women at high risk for
      preeclampsia at mid-gestation. Methods: Women between 16 and 22 weeks of
      gestation were screened for eligibility. Patients were recruited if they met
      eligibility criteria indicating high risk for preeclampsia. Investigators
      performed non-invasive sidestream dark field imaging of the sublingual
      microcirculation. Images were analyzed to determine microcirculatory parameters
      (microvascular flow index, perfused vessel density, total vessel density, and
      proportion of perfused vessels). After delivery, charts were reviewed to
      determine if they developed gestational hypertension, preeclampsia or severe
      preeclampsia. Results: Twelve of 66 participants (18.2%) developed preeclampsia
      or severe preeclampsia during the course of their pregnancy. Microvascular flow
      index was not significantly different between participants with normal
      pregnancies and participants with preeclampsia or severe preeclampsia (2.75 +/-
      0.38 vs. 2.80 +/- 0.34, respectively; P = 0.459). Similarly, there were no
      significant differences between groups in the remaining microcirculatory
      parameters. Conclusions: Sidestream dark field imaging of the sublingual
      microcirculation may remain an appropriate tool to identify women at risk for
      preeclampsia, albeit later in pregnancy.

PMID- 29581802
TI  - Fecal Calprotectin: A Comparison of Two Commercial Enzymoimmunoassays and Study
      of Fecal Extract Stability at Room Temperature.
AB  - Background: The aims of the study were: 1) to compare the fecal calprotectin
      (fCal) assay results with CalprolabTM ELISA (HRP) (Calpro AS) versus our routine
      method, EliaTM fluoroenzymoimmunoassay (Thermo Fisher), and 2) to determine
      whether the fCal assay results do not vary following storage of the extract at
      room temperature for 4 days with the Calpro AS buffer, this being the estimated
      shipment time from the home of the patient, and an aspect little studied to date.
      Methods: The fCal was determined in 198 patients divided into three groups:
      inflammatory bowel disease (IBD), organic intestinal disease, and functional
      intestinal disorders. Fecal extraction was carried out using the Roche
      Diagnostics kit with the corresponding specific buffers. Results: The fCal assay
      with the Thermo Fisher method was found to be more sensitive but less specific
      than with the Calpro AS technique. The positive predictive value was low (just
      over 50%), though the negative predictive value was high (over 90%) with both
      methods. The likelihood ratios revealed small but occasionally important pre-
      versus post-test differences. When we compared the two methods, the Spearman
      correlation coefficient (rho) was 0.819 (95% CI: 0.768 - 0.860) (P < 0.0001),
      reflecting a positive correlation. Similarly, when stratifying the fCal results
      into < 50 ug/g, 50 - 100 ug/g and > 100 ug/g, the resulting Cohen's kappa
      coefficient was 0.7766 (95% CI: 0.7025 - 0.8507), reflecting a substantial
      agreement between both methods. The stability of fCal was high in fecal extracts
      with the Calpro AS extraction buffer at room temperature for 4 days, which
      yielded a Spearman correlation coefficient of 0.951 (95% CI: 0.933 - 0.965), when
      the results were compared to those of the recent extracts (P < 0.0001).
      Conclusions: A positive correlation was observed between the two methods. In view
      of the high negative predictive value obtained with fCal, the presence of organic
      disease is highly unlikely in the presence of a normal concentration of this
      marker. We also confirmed the excellent stability of fCal in fecal extracts with
      the Calpro AS extraction buffer stored at room temperature. Thus, and for the
      sake of convenience and hygiene, it would be ideal for the patient to perform the
      extraction at home.

PMID- 29581803
TI  - Effects of a Low Advanced Glycation End Products Diet on Insulin Levels: The
      Feasibility of a Crossover Comparison Test.
AB  - Background: Advanced glycation end products (AGEs) are associated with diabetes
      mellitus. Digested food-derived AGEs have been implicated in the pathogenesis of
      AGE-related disorders, and restricting diet-derived AGEs improves insulin
      resistance in animal models. The AGE content in foods changes according to
      cooking method, and it is higher in baked or oven-fried foods than in those
      prepared by steaming or simmering. Here, we examined the feasibility of crossover
      comparison tests for determining how different cooking methods (normal diet vs.
      low-AGE diet) affect insulin levels in non-diabetic Japanese subjects. Methods:
      Five adult men and women (age, 41 +/- 7 years; body mass index (BMI), 21.7 +/-
      2.6 kg/m2) were enrolled. The following dietary regimen was used: days 1 - 3,
      control meal; day 4, test meal (normal diet vs. low-AGE diet); day 5, washout
      day; and day 6, test meal. On days 4 and 6, blood samples were collected before
      and at 2, 4, and 6 h after meals. Results: Blood levels of N-(carboxymethyl)
      lysine (CML) increased with dietary intake, but the increase was similar for the
      normal diet and low-AGE diet groups. Mean plasma glucose, insulin, triglycerides
      (TG), and CML did not differ significantly between the two groups. The area under
      the curve (AUC) for insulin levels was lower in the low-AGE diet group (d = 0.8).
      The sample size calculated from the effect size of the insulin AUC change was 22.
      Conclusions: Twenty-two subjects may be needed to investigate the changes in
      clinical parameters attributable to cooking method in non-diabetic Japanese
      subjects.

PMID- 29581804
TI  - Anxiety and Depression Among Adult Patients With Diabetic Foot: Prevalence and
      Associated Factors.
AB  - Background: Diabetic foot is a frequent complication of diabetes mellitus with
      subsequent disturbances in the daily life of the patients. The co-existence of
      depression and anxiety among diabetic foot patients is a common phenomenon and
      the role of each of them in perpetuating the other is highlighted in the
      literature. Our study aimed to determine the prevalence rates of anxiety and
      depression, and to examine the associated risk factors among diabetic foot
      patients. Methods: This is a cross-sectional study. A total of 260 diabetic foot
      patients in the Diabetic Foot Clinic at the National Center for Diabetes,
      Endocrinology and Genetics (NCDEG), Amman, Jordan, participated in the study.
      Sociodemographic and health data were gathered through review of medical charts
      and a structured questionnaire. Depression and anxiety status were also assessed.
      The Generalized Anxiety Disorder Scale (GAD-7) was used to screen for anxiety and
      the Patient Health Questionnaire (PHQ-9) was used to screen for depression. A
      cutoff of >= 10 was used for each scale to identify those who tested positive for
      anxiety and depression. Results: Prevalence rate of anxiety was 37.7% and that of
      depression was 39.6%. Multiple logistic regression analysis showed that anxiety
      is positively associated with duration of diabetes of < 10 years (P = 0.01), with
      >= three comorbid diseases (P = 0.00), and HbA1c level of > 7% (P = 0.03).
      Multiple logistic regression analysis also showed that depression is positively
      associated with patients of < 50 years of age (P = 0.03), females (P = 0.01),
      current smokers (P = 0.01), patients with foot ulcer duration >= 7 months (P =
      0.00), with >= three comorbid diseases (P = 0.00) than their counterparts.
      Conclusions: Anxiety and depression are widely prevalent among diabetic foot
      patients. Mental health status of those patients gets even worse among those
      suffering other comorbid diseases, which was a finding that requires special
      attention in the management of patients with diabetic foot.

PMID- 29581805
TI  - The Role of Urinary Neutrophil Gelatinase-Associated Lipocalin in Predicting
      Acute Kidney Dysfunction in Patients With Liver Cirrhosis.
AB  - Background: Early detection of acute kidney dysfunction (AKD) in cirrhotic
      patients is crucial. Urinary neutrophil gelatinase-associated lipocalin (uNGAL)
      has been identified as an early marker of AKD. The aim of the study was to
      evaluate serial uNGAL as a marker and predictor of AKD in liver cirrhosis
      patients. Methods: Serial uNGAL and serum creatinine (sCr) levels were measured
      daily during the first 6 days of admission. Furthermore, sCr levels and the
      estimated glomerular filtration rate (eGFR) were measured after 3 - 6 weeks. The
      uNGAL levels in patients with and without abnormal sCr were compared. Results:
      Fifty-seven consecutive cirrhotic patients were enrolled in the study. Eight of
      14 patients (57%) who developed abnormal uNGAL level also had abnormal sCr level
      (odds ratio (OR) = 3.4, 95% CI: 0.99 - 12.03, P = 0.05). After 6 weeks, 41% of
      patients exhibited an abnormal uNGAL level and abnormal sCr (OR = 6.7, 95% CI:
      1.55 - 28.85, P = 0.01). Area under the curve (AUROC) and the best cut-off point
      for highest NGAL in 6 days were 0.64 and 72.55 ng/mL, respectively. Conclusions:
      There is a modest association between highest uNGAL in the first 6 days of
      admission and sCr at week 6 in all participants. This may indicate that in
      cirrhotic patients, uNGAL level during the first 6 days of admission has a
      potential predictability for the development of high sCr and low eGFR 6 weeks
      later. The AUROC of 0.64 quantifies the overall ability of uNGAL to discriminate
      between those individuals who will have a raised sCr levels and those who will
      not.

PMID- 29581806
TI  - Accuracy of Three-Dimensional Planning in Surgery-First Orthognathic Surgery:
      Planning Versus Outcome.
AB  - Background: The benefit of computer-assisted planning in orthognathic surgery
      (OGS) has been extensively documented over the last decade. This study aimed to
      evaluate the accuracy of three-dimensional (3D) virtual planning in surgery-first
      OGS. Methods: Fifteen patients with skeletal class III malocclusion who underwent
      bimaxillary OGS with surgery-first approach were included. A composite skull
      model was reconstructed using data from cone-beam computed tomography and
      stereolithography from a scanned dental cast. Surgical procedures were simulated
      using Simplant O&O software, and the virtual plan was transferred to the
      operation room using 3D-printed splints. Differences of the 3D measurements
      between the virtual plan and postoperative results were evaluated, and the
      accuracy was reported using root mean square deviation (RMSD) and the Bland
      Altman method. Results: The virtual planning was successfully transferred to
      surgery. The overall mean linear difference was 0.88 mm (0.79 mm for the maxilla
      and 1 mm for the mandible), and the overall mean angular difference was 1.16
      degrees . The RMSD ranged from 0.86 to 1.46 mm and 1.27 degrees  to 1.45 degrees
      , within the acceptable clinical criteria. Conclusion: In this study, virtual
      surgical planning and 3D-printed surgical splints facilitated the diagnosis and
      treatment planning, and offered an accurate outcome in surgery-first OGS.

PMID- 29581808
TI  - Standardized Reporting System Use During Handoffs Reduces Patient Length of Stay
      in the Emergency Department.
AB  - Background: Emergency department (ED) shift handoffs are potential sources of
      delay in care. We aimed to determine the impact that using standardized reporting
      tool and process may have on throughput metrics for patients undergoing a
      transition of care at shift change. Methods: We performed a prospective, pre- and
      post-intervention quality improvement study from September 1 to November 30,
      2015. A handoff procedure intervention, including a mandatory workshop and
      personnel training on a standard reporting system template, was implemented. The
      primary endpoint was patient length of stay (LOS). A comparative analysis of
      differences between patient LOS and various handoff communication methods were
      assessed pre- and post-intervention. Communication methods were entered a
      multivariable logistic regression model independently as risk factors for patient
      LOS. Results: The final analysis included 1,006 patients, with 327 comprising the
      pre-intervention and 679 comprising the post-intervention populations. Bedside
      rounding occurred 45% of the time without a standard reporting during pre
      intervention and increased to 85% of the time with the use of a standard
      reporting system in the post-intervention period (P < 0.001). Provider time
      (provider-initiated care to patient care completed) in the pre-intervention
      period averaged 297 min, but decreased to 265 min in the post-intervention period
      (P < 0.001). After adjusting for other communication methods, the use of a
      standard reporting system during handoff was associated with shortened ED LOS (OR
      = 0.60, 95% CI 0.40 - 0.90, P < 0.05). Conclusions: Standard reporting system use
      during emergency physician handoffs at shift change improves ED throughput
      efficiency and is associated with shorter ED LOS.

PMID- 29581807
TI  - The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver
      Disease.
AB  - Background: Patients with liver cirrhosis often exhibit zinc deficiency. Although
      zinc is involved in many bioactivities, many aspects of clinical implications of
      zinc deficiency in liver cirrhosis remain unclear. We aimed to reveal the
      prevalence and implications of zinc deficiency in liver cirrhosis by assessing
      associations with parameters such as clinical symptoms and laboratory data.
      Methods: In 235 cirrhosis patients enrolled at multiple medical institutions in
      2009, we assessed how blood zinc levels were associated with their clinical
      symptoms, patients characteristics, and liver function test results. Results:
      Blood zinc levels were most strongly correlated with blood albumin levels among
      the study parameters (r = 0.587, P < 0.0001). When blood albumin levels were <=
      3.5 g/dL, blood zinc levels were < 70 MUg/dL in 88% of patients. Additionally,
      significant correlations were observed with age (r = -0.253, P = 0.0014),
      aspartate aminotransferase levels (r = -0.254, P = 0.0020), total bilirubin
      levels (r = -0.222, P = 0.0053), prothrombin time (r = -0.255, P = 0.0029),
      branched-chain amino acid to tyrosine ratio (r = 0.357, P < 0.0001), Child-Pugh
      score (r = 0.469, P < 0.0001), ammonia levels (r = -0.246, P = 0.0028), and total
      cholesterol levels (r = 0.314, P < 0.0001). Blood zinc levels were significantly
      lower in patients with edema/ascites (P < 0.0001), those with hepatic
      encephalopathy (P = 0.0215), those receiving oral diuretics (P = 0.0045), and
      those receiving oral branched-chain amino acids (P < 0.0001) than in those
      without these conditions. Conclusions: Zinc deficiency is prevalent in cirrhosis
      patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can
      be an indicator of zinc deficiency. Thus, cirrhosis patients exhibiting a
      nitrogen metabolic disorder should be examined for the presence of zinc
      deficiency.

PMID- 29581809
TI  - Autoimmune Diabetes Associated With Pembrolizumab: A Review of Published Case
      Reports.
AB  - The utility of immunotherapy, such as pembrolizumab, is becoming essential in the
      treatment of certain cancers. Pembrolizumab works through binding of programmed
      cell death 1 receptor that blocks the binding of the programmed cell death ligand
      1 and is commonly used in non-small cell lung cancer and melanoma. Pembrolizumab
      has been reported to be associated with multiple adverse reactions such as
      pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism,
      nephritis, and type 1 diabetes; however, pembrolizumab causing type 1 diabetes
      was only reported in 0.1% of the patients in clinical trials. A review of the
      literature generated 1,001 unique citations of which six reported cases of
      autoimmune diabetes associated with pembrolizumab were selected and compared.
      Review of the cases showed no sexual predilection and the average age of onset
      was 58 years old. The majority of the patients were treated for melanoma (5/6
      cases), initially presented with diabetic ketoacidosis (4/6 cases), and had at
      one point taken ipilimumab (4/6 cases). There was no association found between
      the number of treatments received and the development of diabetes. With the
      increasing use of pembrolizumab in cancer treatment regular blood glucose
      monitoring during treatment, especially in patients who had also taken
      ipilimumab, may prevent the onset of this life-threatening complication.

PMID- 29581810
TI  - The Clinical Efficacy of Prostate Cancer Screening in Worldwide and Iran:
      Narrative Review.
AB  - Prostate cancer (CaP) imposes a great health burden on men, while its incidence
      has significantly increased in recent years. The screening program for CaP is
      still controversial and recent large trials have failed to present a significant
      reduction in prostate-specific mortality and all-cause mortality. An entire body
      of data obtained from worldwide studies conducted on CaP screening is required to
      better evaluate health policy decisions and patient decision-making. In current
      review, the clinical efficacy of screening programs on CaP was discussed in
      numerous parts of the world, such as in the US, Europe, and Asia, to provide an
      updated screening recommendation. Finally, we discuss about CaP screening status
      in Iran and update the screening recommendation in Iran.

PMID- 29581811
TI  - Lymphocyte to Monocyte Ratio and Modified Glasgow Prognostic Score Predict
      Prognosis of Lung Adenocarcinoma Without Driver Mutation.
AB  - Background: Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio
      (LMR) and modified Glasgow prognostic score (mGPS) are useful prognostic markers
      based on host-related systemic inflammatory response. They have been shown as
      independent prognostic biomarkers in various cancers, including non-small cell
      lung cancer. However, there has been little evidence for a specific population of
      pulmonary adenocarcinoma without active epidermal growth factor receptor (EGFR)
      mutation. Methods: We retrospectively reviewed 159 patients who met the following
      criteria: histologically or cytologically diagnosed adenocarcinoma, confirmed
      wild-type EGFR, started first-line cytotoxic chemotherapy between July 2007 and
      March 2017 at our hospital, and c-stage IIIB or IV. We compared overall survival
      (OS) between dichotomized groups by the optimal cut-off points of NLR and LMR,
      and mGPS 0 - 1 vs. 2. Univariate and multivariate Cox proportional hazard
      analyses also detected prognostic factors for OS. Results: As favorable
      prognostic factors for OS, multivariate analysis detected Eastern Cooperative
      Oncology Group performance status (ECOG PS) 0 - 1 (hazard ratio (HR) 3.43, 95%
      confidence interval (CI): 2.12 - 5.53; P < 0.01), LMR >= 1.97 (HR 0.39, 95% CI:
      0.21 - 0.72; P < 0.01) and mGPS 0 - 1 (HR 1.95, 95% CI: 1.20 - 3.16; P < 0.01).
      The OS of LMR >= 1.97 and mGPS 0 - 1 groups were significantly longer than those
      of LMR < 1.97 and mGPS 2 groups, respectively. We divided 159 patients into three
      groups, both LMR >= 1.97 and mGPS 0 - 1, either LMR >= 1.97 or mGPS 0 - 1 and
      both LMR < 1.97 and mGPS 2. The OS of both LMR < 1.97 and mGPS 2 was
      significantly shorter than the other two groups. After adjustment for age, sex,
      ECOG PS, sodium, alkaline phosphatase and NLR, multivariate analysis found both
      LMR < 1.97 and mGPS 2 as an independent poor prognostic combination in comparison
      with both LMR >= 1.97 and mGPS0-1 (HR 5.98, 95% CI: 2.64 - 13.5; P < 0.01).
      Conclusions: LMR and mGPS are independent prognostic markers for pulmonary
      adenocarcinoma with wild-type EGFR. Combination of LMR and mGPS can stratify
      patients according to prognosis.

PMID- 29581812
TI  - Inhibition of ERK1/2 or AKT Activity Equally Enhances Radiation Sensitization in
      B16F10 Cells.
AB  - Background: The aim of the study was to evaluate the radiation sensitizing
      ability of ERK1/2, PI3K-AKT and JNK inhibitors in highly radiation resistant and
      metastatic B16F10 cells which carry wild-type Ras and Braf. Methods: Mouse
      melanoma cell line B16F10 was exposed to 1.0, 2.0 and 3.0 Gy of electron beam
      radiation. Phosphorylated ERK1/2, AKT and JNK levels were estimated by ELISA.
      Cells were exposed to 2.0 and 3.0 Gy of radiation with or without prior
      pharmacological inhibition of ERK1/2, AKT as well as JNK pathways. Cell death
      induced by radiation as well as upon inhibition of these pathways was measured by
      TUNEL assay using flow cytometry. Results: Exposure of B16F10 cells to 1.0, 2.0
      and 3.0 Gy of electron beam irradiation triggered an increase in all the three
      phosphorylated proteins compared to sham-treated and control groups. B16F10 cells
      pre-treated with either ERK1/2 or AKT inhibitors equally enhanced radiation
      induced cell death at 2.0 as well as 3.0 Gy (P < 0.001), while inhibition of JNK
      pathway increased radiation-induced cell death to a lesser extent. Interestingly
      combined inhibition of ERK1/2 or AKT pathways did not show additional cell death
      compared to individual ERK1/2 or AKT inhibition. This indicates that ERK1/2 or
      AKT mediates radiation resistance through common downstream molecules in B16F10
      cells. Conclusions: Even without activating mutations in Ras or Braf genes,
      ERK1/2 and AKT play a critical role in B16F10 cell survival upon radiation
      exposure and possibly act through common downstream effector/s.

PMID- 29581813
TI  - Atypical Presentation of Acute Myeloid Leukemia.
AB  - We present a case of a 48-year-old male who presented with worsening pleuritic
      chest pain for 2 h. He also complained of fever, malaise, headache and severe
      neck pain. Electrocardiogram (ECG) showed ST segment elevation in leads I, II,
      aVL and V5 with PR elevation and ST depression in aVR. On admission, troponin-I
      was 14.8 ng/mL. Based on ECG changes, elevated troponin and family history of
      early coronary artery disease, the patient was emergently taken to cardiac
      catheterization lab. Angiography showed non-obstructive coronaries, mild
      hypokinesis of mid inferior and anterolateral wall with ejection fraction (EF) of
      40-45%. Based on above presentation and angiography findings, the diagnosis of
      acute myopericarditis was made. He was started on colchicine and ibuprofen. The
      other workup to determine etiology of myopericarditis was negative as shown
      below. Given the history of fever, headache and worsening neck pain, we also
      became suspicious of meningitis. Lumbar puncture was performed which was
      negative. On the day of admission, he was found to have blasts on complete blood
      count and peripheral smear. Bone marrow biopsy and flow cytometry confirmed the
      diagnosis of acute myeloid leukemia (AML). He received induction and salvage
      therapy. Repeat bone marrow confirmed complete remission and normal cytogenetics.
      Although pericardial or myocardial biopsies are unavailable for our patient, in
      the absence of other causes, it does appear that his acute myopericarditis was
      associated with AML.

PMID- 29581814
TI  - A Rare Case of Colonic Metastases From Tonsillar Carcinoma: Case Report and
      Review of Literature.
AB  - The incidence of tonsillar cancer has increased by four times in the United
      States over the last few decades likely due to recent increase in human papilloma
      virus (HPV) infections. The stage of the tumor predicts likelihood of metastasis,
      with advanced stages associated with higher chances of metastasis. The squamous
      cell carcinomas (SCCs) of the head and neck commonly metastasize to the lung,
      bone and liver in descending order. Tonsillar cancer rarely involves the small
      bowel and our review of the literature did not reveal any reported case of
      metastasis to the colon/large bowel. Our patient had locally metastatic tonsillar
      cancer, treated with partial pharyngectomy and selective neck dissection but
      later developed several bone and colonic metastases concurrently, likely
      secondary to hematogeneous dissemination after a few months of therapy. To the
      best of our knowledge, large bowel metastasis from head and neck SCC has never
      been reported in the literature. In these patients presenting with atypical
      gastrointestinal symptoms, a high index of suspicion should be maintained to
      determine the extent of metastasis and identify other metastatic sites.

PMID- 29581815
TI  - Inter-Rater Reliability of the Retrospectively Assigned Clinical Frailty Scale
      Score in a Geriatric Outreach Population.
AB  - Background: Frailty, a common clinical syndrome in older adults associated with
      increased risk of poor health outcomes, has been retrospectively calculated in
      previous publications; however, the reliability of retrospectively assigned
      frailty scores has not been established. The aim of this study was to see if
      frailty scores, based on chart review data, agreed with clinician-determined
      scores based on a comprehensive geriatric assessment. Methods: Per standard
      practice, all patients seen by one nurse clinician (JW) from the Southwestern
      Ontario Regional Geriatric Program, a tertiary care-based outreach service,
      between August 15, 2013 and December 31, 2015 received a comprehensive geriatric
      assessment which included the assignment of an interview-based Clinical Frailty
      Scale score (CFS-I). Subsequently, a medical student researcher (JD), blinded to
      the CFS-I, assigned each consenting patient a frailty score based on chart review
      data (CFS-C). The inter-rater reliability of the CFS-I and CFS-C was then
      determined. Results: Of the 41 consented patients, 39 had both a CFS-I and CFSC
      score. The median CFS score was 6, indicating patients were moderately frail and
      required assistance for some basic activities of daily living. Cohen's kappa
      coefficient was 0.64, indicating substantial agreement. Conclusion: CFS scores
      can be reliably assigned retrospectively, thereby strengthening the utility of
      this measure.

PMID- 29581816
TI  - Identifying the Priority Topics for the Assessment of Competence in Care of the
      Elderly.
AB  - Background: With Canada's senior population increasing, there is greater demand
      for family physicians with enhanced skills in Care of the Elderly (COE). The
      College of Family Physicians Canada (CFPC) has introduced Certificates of Added
      Competence (CACs), one being in COE. Our objective is to summarize the process
      used to determine the Priority Topics for the assessment of competence in COE.
      Methods: A modified Delphi technique was used, with online surveys and face-to
      face meetings. The Working Group (WG) of six physicians acted as the nominal
      group, and a larger group of randomly selected practitioners from across Canada
      acted as the Validation Group (VG). The WG, and then the VG, completed electronic
      write-in surveys that asked them to identify the Priority Topics. Responses were
      compiled, coded, and tabulated to identify the topics and to calculate the
      frequencies of their selection. The WG used face-to-face meetings and iterative
      discussion to decide on the final topic names. Results: The correlation between
      the initial Priority Topic list identified by the VG and that identified by the
      WG is 0.6793. The final list has 18 Priority Topics. Conclusion: Defining the
      required competencies is a first step to establishing national standards in COE.

PMID- 29581817
TI  - Medications & Polypharmacy Influence on Recurrent Fallers in Community: a
      Systematic Review.
AB  - The purpose of this systematic review is to summarize information about the
      impact different classes of medications and polypharmacy have on recurrent falls,
      defined as two or more falls in a 12-month period, in community-dwelling older
      adults. After adjustment for confounders such as age, gender, weight or
      depression symptoms, the reviewed studies suggested that older adults who use
      antidepressants, sedatives or hypnotics and anti-epileptics were more likely to
      experience recurrent falls than non-users. Polypharmacy (use of four or more
      prescription medications daily) caused 1.5-2 times higher possibility of
      recurrent falls in older adults. As a high-risk group, recurrent fallers require
      meaningful intervention. Medications are believed to be a modifiable risk factor
      in falls prevention; hence, special consideration should be taken to balance the
      benefit and harm in initiating, continuing or increasing certain classes of
      medications in elderly recurrent fallers.

PMID- 29581818
TI  - A Case for the Standardized Assessment of Testamentary Capacity.
AB  - Background: With an increasingly aged, frail population that holds a
      disproportionate amount of wealth, clinicians (especially those with expertise in
      older adults) may be asked with more frequency to offer a clinical opinion on
      testamentary capacity (TC), the mental capacity to make a will. Method: This
      paper reviews the legal criteria as well as the empirical research on assessment
      tools for determining testamentary capacity (TC). We also review the relevance of
      instruments used for the assessment of other decisional capacities in order to
      evince the potential value of developing a standardized assessment of TC for
      clinician experts. Results: The legal criteria, often referred to as a "test",
      for determining requisite TC (Banks v. Goodfellow) have remained much the same
      since 1870 with minimal clinical input and, as such, there has been little
      development in TC assessment instruments. Decisional instruments designed to
      assess Consent to Treatment may have relevance for TC. Conclusion: We make the
      case for a semi-structured interview that includes standardized criteria for the
      legal test for TC, supplemented by a validated brief neuropsychological
      assessment, which together comprise a Contemporaneous Assessment Instrument (CAI)
      for TC.

PMID- 29581819
TI  - A Slow-Growing Hand Mass.

PMID- 29581820
TI  - Editorial - The 3rd International Conference on Sebaceous Gland, Acne, Rosacea
      and Related Disorders.

PMID- 29581822
TI  - Extended therapy breaks from VEGFR TKI therapy in renal cell carcinoma: Sometimes
      less is more.

PMID- 29581823
TI  - Serum microRNAs - potent biomarkers for radiation biodosimetry.

PMID- 29581821
TI  - Unraveling the Burden of Iron in Neurodegeneration: Intersections with Amyloid
      Beta Peptide Pathology.
AB  - Iron overload is a hallmark of many neurodegenerative processes such as
      Alzheimer's, Parkinson's, and Huntington's diseases. Unbound iron accumulated as
      a consequence of brain aging is highly reactive with water and oxygen and
      produces reactive oxygen species (ROS) or free radicals. ROS are toxic compounds
      able to damage cell membranes, DNA, and mitochondria. Which are the mechanisms
      involved in neuronal iron homeostasis and in neuronal response to iron-induced
      oxidative stress constitutes a cutting-edge topic in metalloneurobiology.
      Increasing our knowledge about the underlying mechanisms that operate in iron
      accumulation and their consequences would shed light on the comprehension of the
      molecular events that participate in the pathophysiology of the abovementioned
      neurodegenerative diseases. In this review, current evidences about iron
      accumulation in the brain, the signaling mechanisms triggered by metal overload,
      as well as the interaction between amyloid beta (Abeta) and iron, will be
      summarized.

PMID- 29581824
TI  - Breast cancer cells exploit mitophagy to exert therapy resistance.

PMID- 29581825
TI  - Novel inhibitor candidates of TRPV2 prevent damage of dystrophic myocytes and
      ameliorate against dilated cardiomyopathy in a hamster model.
AB  - Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a
      principal candidate for abnormal Ca2+-entry pathways, which is a potential target
      for therapy of muscular dystrophy and cardiomyopathy. Here, an in silico drug
      screening and the following cell-based screening to measure the TRPV2 activation
      were carried out in HEK293 cells expressing TRPV2 using lead compounds (tranilast
      or SKF96365) and off-patent drug stocks. We identified 4 chemical compounds
      containing amino-benzoyl groups and 1 compound (lumin) containing an
      ethylquinolinium group as candidate TRPV2 inhibitors. Three of these compounds
      inhibited Ca2+ entry through both mouse and human TRPV2, with IC50 of less than
      10 MUM, but had no apparent effect on other members of TRP family such as TRPV1
      and TRPC1. Particularly, lumin inhibited agonist-induced TRPV2 channel activity
      at a low dose. These compounds inhibited abnormally increased Ca2+ influx and
      prevented stretch-induced skeletal muscle damage in cultured myocytes from
      dystrophic hamsters (J2N-k). Further, they ameliorated cardiac dysfunction, and
      prevented disease progression in vivo in the same J2N-k hamsters developing
      dilated cardiomyopathy as well as muscular dystrophy. The identified compounds
      described here are available as experimental tools and represent potential
      treatments for patients with cardiomyopathy and muscular dystrophy.

PMID- 29581826
TI  - Increased visceral fat volume raises the risk for recurrence of hepatocellular
      carcinoma after curative treatment.
AB  - Obesity is a risk factor for the development of hepatocellular carcinoma (HCC).
      This study aimed to assess the influence of visceral fat on the recurrence of HCC
      after curative treatment. In 207 curative cases of HCC, the cross-sectional areas
      of visceral and subcutaneous fat mass on the computed tomographic image at the
      fourth lumbar vertebra were normalized by the square of the height to obtain the
      visceral fat mass index (VFMI) and the subcutaneous fat mass index (SFMI),
      respectively. Whether VFMI and SFMI contributed to recurrence of HCC and overall
      survival was analyzed using a Cox proportional hazards model. Increased VFMI was
      significantly associated with recurrence of HCC (P = 0.006), whereas SFMI was not
      (P = 0.502). When the patients were divided based on the optimal cut off value
      for VFMI (47.2 cm2/m2), obtained from maximally selected rank statistics to best
      predict the risk for recurrence, the higher VFMI group (n = 79) had more
      probability of recurrence than the lower VFMI group (n = 128) (log rank test, P =
      0.002). There were significant differences in body mass index (P < .0001), SFMI
      (P < .0001), L3 skeletal muscle index (P < .0001), platelet count (P = 0.003),
      hemoglobin A1c (P < .0001), triglycerides (P = 0.004), serum leptin (P = 0.043),
      and underlying liver disease (P < .0001) between the groups. Neither VFMI (P =
      0.689) nor SFMI (P = 0.117) significantly contributed to overall survival. VFMI,
      which is involved in obesity and its related metabolic disorders such as
      diabetes, hyperlipidemia, and adipokine imbalance, is an extremely promising
      indicator that can predict the risk of recurrence of HCC after curative
      treatment.

PMID- 29581827
TI  - Hypertension predicts a poor prognosis in patients with esophageal squamous cell
      carcinoma.
AB  - Background: We investigated the relationship between the preoperative
      hypertension and prognosis of esophageal squamous cell cancer (ESCC) patients who
      had underwent esophagectomy. Results: We detected 52% patients with hypertension,
      including 317 patients with newly diagnosed hypertension and 194 patients with
      history of hypertension. Compared with patients of normal blood pressure, all
      patients with hypertension and newly diagnosed hypertension were observed to have
      worse overall and ESCC-specific survival outcome (p < 0.05). After adjusted in
      multivariate Cox regression analysis, hypertension (HR: 1.343, 95% CI: 1.064,
      1.695; HR: 1.315, 95% CI: 1.039, 1.664) and newly diagnosed hypertension (HR:
      1.414, 95% CI: 1.095, 1.826; HR: 1.420, 95% CI: 1.098, 1.836) were inversely
      associated with overall and ESCC-specific survival outcome, respectively. While
      no association was found between history of hypertension and overall or ESCC
      specific survival outcome (HR: 1.229, 95% CI: 0.892, 1.694; HR: 1.132, 95% CI:
      0.812, 1.578). Conclusions: Hypertension was an independent risk factor and
      resulted in inferior prognosis for ESCC patients who had underwent esophagectomy.
      Methods: A total of 982 ESCC patients who had underwent esophagectomy from August
      2010 to December 2015 were enrolled in our study with a follow up of 6 years. The
      Kaplan-Meier method and log-rank test were respectively used to calculate and
      compare survival rate, and Cox proportional hazards regression model was applied
      to identify independent prognostic factors.

PMID- 29581828
TI  - Genetic variation of CXCR4 and risk of coronary artery disease: epidemiological
      study and functional validation of CRISPR/Cas9 system.
AB  - Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, while
      coronary artery disease (CAD) account for a large part of CVDs. Vascular CXCR4
      could limit atherosclerosis by maintaining arterial integrity. Here, we conducted
      a population-based, case-control study to evaluate the associations of common
      genetic variation within the CXCR4 gene (rs2228014, rs117600832, rs2471859, and
      rs2322864) with CAD risk in a Chinese population. We found that CXCR4 rs2228014
      was significantly associated with 1.29-fold increased risk of CAD (A vs G: OR =
      1.29; 95% CI = 1.07-1.55; P = 0.007). The subjects with genotype AA (OR = 1.98;
      95% CI = 1.03-3.81; P = 0.041) and AG (OR = 1.27; 95% CI = 1.02-1.58; P = 0.030)
      have higher risk of CAD, compared with those with genotype GG. Furthermore, both
      in the CAD patients with diabetes and those without diabetes, rs2228014 was
      significantly associated with increased risk of CAD (P < 0.05). Additionally, we
      also validated the significant association for rs2322864 (C vs T: OR = 1.20; 95%
      CI = 1.00-1.44; P = 0.046). Knockout of CXCR4 gene could significantly impair the
      capacity of cholesterol efflux (P < 0.01). These findings strongly suggest that
      CXCR4 polymorphisms might contribute to CAD susceptibility, and the exact
      biological mechanism awaits further research.

PMID- 29581829
TI  - Cystatin A suppresses tumor cell growth through inhibiting epithelial to
      mesenchymal transition in human lung cancer.
AB  - Cystatin A (CSTA), belonging to type 1 cystatin super-family, is expressed
      primarily in epithelial and lymphoid tissues for protecting cells from
      proteolysis of cytoplasmic and cytoskeletal proteins by cathepsins B, H and L.
      CSTA acts as a tumor suppressor in esophageal cancer, however, its role in lung
      cancer has not yet been elucidated. Here we found that CSTA was down-regulated in
      all lung cancer cell lines compared to normal lung epithelial cells. CSTA was
      restored in most lung cancer cell lines after treatment with demethylation agent
      5-aza-2-deoxycytidine and deacetylation agent Trichostatin. Bisulfite sequencing
      revealed that CSTA was partially methylated in the promoter and exon 1. In
      primary lung tumors, squamous cell carcinoma (SCC) significantly expressed more
      CSTA compared to adenocarcinoma (p<0.00001), and higher expression of CSTA was
      significantly associated with lower tumor grade (p<0.01). CSTA stable
      transfection reduced the activity of cathepsin B and inhibited the ability of
      colony formation, migration and invasion, and enhanced gemcitabine-induced
      apoptosis. CSTA overexpression resulted in reduced activity of ERK, p-38, and
      AKT. Additionally, CSTA overexpression led to a mesenchymal to epithelial
      transition (MET) and prevented the TGF-beta1-induced epithelial to mesenchymal
      transition (EMT) through inhibiting the ERK/MAPK pathway. In conclusion, our date
      indicate 1) epigenetic regulation is associated with CSTA gene silencing; 2) CSTA
      exerts tumor suppressive function through inhibiting MAPK and AKT pathways; 3)
      Overexpression of CSTA leads to MET and prevents TGF-beta1-induced EMT by
      modulating the MAPK pathway; 4) CSTA may be a potential biomarker for lung SCC
      and tumor differentiation.

PMID- 29581830
TI  - Orthotopic hepatic cancer: radiofrequency hyperthermia-enhanced intratumoral
      herpes simplex virus-thymidine kinase gene therapy.
AB  - Purpose: To validate the feasibility of using interventional radiofrequency
      hyperthermia(RFH) to enhance herpes simplex virus-thymidine kinase (HSV
      TK)/ganciclovir (GCV) gene therapy of rat orthotopic hepatic cancer. Material and
      Methods: Rat hepatocellular carcinoma cells (MCA-RH-7777) were transduced with
      lentivirus/luciferase gene for optical imaging. In-vitro experiments with the
      luciferase cells and in-vivo experiments on rats with orthotopic hepatic tumors
      were divided into four treatment groups: (i) HSV-TK/GCV-mediated gene therapy
      combined with RFH; (ii) gene therapy alone; (iii) RFH alone; and (iv) phosphate
      buffered saline (PBS). Cell viability was evaluated by MTS assay and confocal
      microscopy, and HSV-TK gene expression in cells and tumors was quantified by
      western blotting. Bioluminescent optical imaging and ultrasound imaging were used
      to monitor and compare the photon signal and tumor size changes among different
      treatment groups overtime, respectively. The imaging findings were correlated
      with histology. Results: For in-vitro experiments, the combination therapy group
      (gene therapy + RFH) demonstrated the lowest cell proliferation by MTS assay,
      compared to the gene therapy alone, RFH alone, and PBS (26.1+/-3.2% vs 50.4+/
      4.6% vs 82.9+/-6.3% vs 100%, p<0.01). The combination therapy group also showed
      fewer survived cells by the confocal microscopy and the lowest bioluminescent
      signal by the optical imaging. For in-vivo experiments, the combination therapy
      group demonstrated a significantly decreased signal intensity on the
      bioluminescent optical imaging (0.57+/-0.09, 1.06+/-0.10 vs 3.43+/-0.27 vs 3.85+/
      0.12, p<0.05) and smallest tumor volume by ultrasound imaging (0.28+/-0.11 vs
      1.28+/-0.23vs 4.64+/-0.35 vs 6.37+/-0.36, p<0.05), compared to the other three
      groups. Additionally, these imaging findings correlated well with the
      histological confirmation. Conclusion: It is feasible to use RFH to enhance HSV
      TK/GCV gene therapy of hepatic tumors in in-vitro and in-vivo settings, as
      assessed by molecular imaging. This technical development may provide a novel
      opportunity for effective treatment of liver malignancies by employing
      simultaneous integration of radiofrequency technology, interventional oncology,
      and direct intratumoral gene therapy.

PMID- 29581831
TI  - Association analysis of SNPs present in plasma with adverse events and population
      pharmacokinetics in Chinese sunitinib treated patients with renal cell carcinoma.
AB  - Background: Sunitinib is a tyrosine kinase inhibitor with effective therapeutic
      outcomes in patients with renal-cell carcinoma. The study were to analyze the
      association of single-nucleotide polymorphisms present in cell-free DNA and
      pharmacokinetics with sunitinib treatment-emergent adverse events in Chinese
      patients with renal-cell carcinoma. Materials and Methods: We genotyped 8 keys
      SNPs in 6 candidate genes. The plasma concentrations of sunitinib and N-desethyl
      sunitinib were measured using a high performance liquid chromatography-tandam
      mass spectrometry method. Correlations between the single-nucleotide
      polymorphisms and adverse events were investigated by univariate and multivariate
      logistic regression and we quantitatively evaluated the effect of single
      nucleotide polymorphisms on the pharmacokinetics of sunitinib by using a
      population PK model. Results: Necessary dose reductions of sunitinib were
      significantly correlated with SNP rs1933437 in FLT3. A higher severity of AEs
      were collected with SNP rs2032582 in ABCB1 and rs1800812 in PDGFRalpha.
      Thrombocytopenia was collected with rs1800812 in PDGFRalpha. Our study provides a
      population PK model of sunitinib with the ABCB1 genotype as a predictive
      covariate for apparent oral clearance. Conclusions: Our study preliminarily
      confirmed the hypothesis that the pharmacokinetics of sunitinib is affected by
      the SNPs of enzyme in Chinese renal-cell carcinoma patients, and this affects the
      different distribution and severity of adverse events of sunitinib.

PMID- 29581832
TI  - AP-1 confers resistance to anti-cancer therapy by activating XIAP.
AB  - The underlying cause of treatment failure in many cancer patients is intrinsic
      and acquired resistance to chemotherapy. Recently, histone deacetylase (HDAC)
      inhibitors have developed into a promising cancer treatment. However, resistance
      mechanism induced by HDAC inhibitors remains largely unknown. Here we report that
      a HDAC inhibitor, JNJ-2648158 induced transcription of XIAP by activating AP-1
      expression, which conferring resistance to chemotherapeutics. Our results showed
      that high expression of c-Fos caused by HDAC inhibitor promoted AP-1 formation
      during acquired resistance towards chemo-drugs, indicating an extremely poor
      clinical outcome in breast cancers and liver cancers. Our study reveals a novel
      regulatory mechanism towards chemo-drug resistance, and suggests that XIAP may
      serve as a potential therapeutic target in those chemo-resistant cancer cells.

PMID- 29581833
TI  - Perspectives of patients and physicians about neuroendocrine tumors. A
      qualitative study.
AB  - Purpose: Gastrointestinal neuroendocrine tumors (NETs) are rare, complex to
      manage, and often have a chronic course. Qualitative methods are a tool of choice
      for focusing on patients' and physicians' points of view especially when dealing
      with a complex and rare disease. Nonetheless, they remain undeveloped in research
      related to NETs. This study aimed to explore the experience of NETs among both
      patients and their physicians and to cross their perspectives for the purpose of
      finding pathways to improving care. Results: Our analysis found two themes: (1)
      the questions raised by this disease, and (2) the complex experience of this
      singular disease. Our findings underlined the experience of confusion found among
      patients regarding the patient's unusual somatic experience and around the
      question of vocabulary, i.e. the naming of the disease and the semantic field of
      severity in the medical discourse. Conclusion: Means for reducing the confusion
      that patients experience in this disease are needed. The explanations that the
      physician offers to the patient must clarify the issues related to NETs. We
      therefore propose a statement that all physicians can use to support patients
      diagnosed with neuroendocrine tumors to clear up potential confusion. Methods: We
      conducted a qualitative study, based on 40 semi-structured interviews, in a
      specialized department of gastro-pancreatology. Participants, purposively
      selected until data saturation, came from two different sub-samples: (i) patients
      with a metastatic NETs (N = 20) and (ii) their referring physicians (N = 10). The
      data were examined by thematic analysis.

PMID- 29581834
TI  - Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/ mTOR pathways on
      cell migration in MDA-MB-231 cells.
AB  - The study of eukaryotic initiation factor 4E (eIF4E) is a key focus in cancer
      research due to its role in controlling the translation of tumour-associated
      proteins, that drive an aggressive migratory phenotype. eIF4E is a limiting
      component of the eIF4F complex which is a critical determinant for the
      translation of mRNAs. Mitogen-activated protein kinase interacting protein
      kinases (MNK1/2) phosphorylate eIF4E on Ser209, promoting the expression of
      oncogenic proteins, whereas mTORC1 phosphorylates and de-activates the eIF4E
      inhibitor, 4E-BP1, to release translational repression. Here we show that
      inhibiting these pathways simultaneously effectively slows the rate of cell
      migration in breast cancer cells. However, a molecular hybridisation approach
      using novel, cleavable dual MNK1/2 and PI3K/mTOR inhibiting hybrid agents was
      less effective at slowing cell migration.

PMID- 29581835
TI  - Cell internalization of 7-ketocholesterol-containing nanoemulsion through LDL
      receptor reduces melanoma growth in vitro and in vivo: a preliminary report.
AB  - Oxysterols are cholesterol oxygenated derivatives which possess several
      biological actions. Among oxysterols, 7-ketocholesterol (7KC) is known to induce
      cell death. Here, we hypothesized that 7KC cytotoxicity could be applied in
      cancer therapeutics. 7KC was incorporated into a lipid core nanoemulsion. As a
      cellular model the murine melanoma cell line B16F10 was used. The nanoparticle
      (7KCLDE) uptake into tumor cells was displaced by increasing amounts of low
      density-lipoproteins (LDL) suggesting a LDL-receptor-mediated cell
      internalization. 7KCLDE was mainly cytostatic, which led to an accumulation of
      polyploid cells. Nevertheless, a single dose of 7KCLDE killed roughly 10% of
      melanoma cells. In addition, it was observed dissipation of the transmembrane
      potential, evidenced with flow cytometry; presence of autophagic vacuoles,
      visualized and quantified with flow cytometry and acridine orange; and presence
      of myelin figures, observed with ultrastructural microscopy. 7KCLDE impaired
      cytokenesis was accompanied by changes in cellular morphology into a
      fibroblastoid shape which is supported by cytoskeletal rearrangements, as shown
      by the increased actin polymerization. 7KCLDE was injected into B16 melanoma
      tumor-bearing mice. 7KCLDE accumulated in the liver and tumor. In melanoma tumor
      7KCLDE promoted a >50% size reduction, enlarged the necrotic area, and reduced
      intratumoral vasculature. 7KCLDE increased the survival rates of animals, without
      hematologic or liver toxicity. Although more pre-clinical studies should be
      performed, our preliminary results suggested that 7KCLDE is a promising novel
      preparation for cancer chemotherapy.

PMID- 29581836
TI  - RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival
      outcomes in breast cancer.
AB  - Hippo pathway target, YAP has emerged as an important player in solid tumor
      progression. Here, we identify RUNX1 and RUNX3 as novel negative regulators of
      oncogenic function of YAP in the context of breast cancer. RUNX proteins are one
      of the first transcription factors identified to interact with YAP. RUNX1 or
      RUNX3 expression abrogates YAP-mediated pro-tumorigenic properties of mammary
      epithelial cell lines in an interaction dependent manner. RUNX1 and RUNX3 inhibit
      YAP-mediated migration and stem-ness properties of mammary epithelial cell lines
      by co-regulating YAP-mediated gene expression. Analysis of whole genome
      expression profiles of breast cancer samples revealed significant co-relation
      between YAP-RUNX1/RUNX3 expression levels and survival outcomes of breast cancer
      patients. High RUNX1/RUNX3 expression proved protective towards YAP-dependent
      patient survival outcomes. High YAP in breast cancer patients' expression
      profiles co-related with EMT and stem-ness gene signature enrichment. High
      RUNX1/RUNX3 expression along with high YAP reflected lower enrichment of EMT and
      stem-ness signatures. This antagonistic activity of RUNX1 and RUNX3 towards
      oncogenic function of YAP identified in mammary epithelial cells as well as in
      breast cancer expression profiles gives a novel mechanistic insight into oncogene
      tumor suppressor interplay in the context of breast cancer progression. The novel
      interplay between YAP, RUNX1 and RUNX3 and its significance in breast cancer
      progression can serve as a prognostic tool to predict cancer recurrence.

PMID- 29581837
TI  - Molecular and clinical features of the TP53 signature gene expression profile in
      early-stage breast cancer.
AB  - Purpose: TP53 signature has a robust predictive performance for prognosis in
      early-stage breast cancer, but the experiment that reported this relied on public
      microarray data and fresh-frozen samples. Before TP53 signature can be used in a
      clinical setting, a simple and low-cost diagnostic system using formalin-fixed
      paraffin-embedded (FFPE) samples is needed. New treatments based on the
      biological characteristics of TP53 signature are expected to follow. Experimental
      Design: TP53 signature was evaluated in 174 FFPE early breast cancer specimens
      using digital quantification via the nCounter technique (NanoString). Patients
      were classified as TP53 signature mutant type (n = 64) or wild type (n = 110).
      Predictive power of TP53 signature was compared with those of other gene
      expression signatures in 153 fresh-frozen samples of the same cohort by RNA-seq.
      The molecular features of TP53 signature were elucidated using TCGA omics data
      and RNA-seq data to explore new therapeutic strategies for patients with TP53
      signature mutant type. Results: TP53 signature was a strong predictor of
      prognosis and was also more accurate than other gene expression signatures and
      independent of other clinicopathological factors. TCGA data analysis showed that
      risk score of TP53 signature was an index of chromosomal and genomic instability
      and that TP53 signature mutant type was associated with higher PD-L1 expression,
      variation in copy numbers, and numbers of somatic mutations. Conclusions: TP53
      signature as diagnosed using the nCounter system is not only a robust predictor
      of prognosis but also a potential predictor of responsiveness to immune
      checkpoint inhibitors.

PMID- 29581838
TI  - High expression of SLCO2B1 is associated with prostate cancer recurrence after
      radical prostatectomy.
AB  - Solute carrier organic anion (SLCO) gene families encode organic anion transport
      proteins, which are transporters that up-take a number of substrates including
      androgens. Among them, high expression of SLCO2B1 is known to associate with the
      resistance to androgen deprivation therapy in prostate cancer (PCa). We
      hypothesized that high expression of SLCO genes enhances PCa progression by
      promoting the influx of androgen. Here, we demonstrated the impact of the
      expression levels of SLCO2B1 on prognosis in localized PCa after radical
      prostatectomy (RP) utilizing 494 PCa cases in The Cancer Genome Atlas (TCGA).
      SLCO2B1 high expression group showed significantly worse Disease-free survival
      (DFS) after RP (p = 0.001). The expression level of SLCO2B1 was significantly
      higher in advanced characteristics including Gleason Score (GS <= 6 vs GS = 7; p
      = 0.047, GS = 7 vs GS >= 8; p = 0.002), pathological primary tumor (pT2 vs pT3/4;
      p < 0.001), and surgical margin status (positive vs negative; p = 0.013),
      respectively. There was a significant difference in DFS between these two groups
      only in GS >= 8 patients (p = 0.006). Multivariate analysis demonstrated that
      only SLCO2B1 expression level was an independent predictor for DFS after RP in GS
      >= 8. SLCO2B1 high expressed tumors in GS >= 8 not only enriched epithelial
      mesenchymal transition (EMT) related gene set, (p = 0.027), as well as Hedgehog
      (p < 0.001), IL-6/JAK/STAT3 (p < 0.001), and K-ras signaling gene sets (p <
      0.001), which are known to promote EMT, but also showed higher expression of EMT
      related genes, including N-cadherin (p = 0.024), SNAIL (p = 0.001), SLUG (p =
      0.001), ZEB-1 (p < 0.001) and Vimentin (p < 0.001). In conclusion, PCa with high
      expression of SLCO2B1 demonstrated worse DFS, which might be due to accelerated
      EMT.

PMID- 29581839
TI  - Excellent outcomes of 2G-TKI therapy after imatinib failure in chronic phase CML
      patients.
AB  - Second-generation tyrosine kinase inhibitors (2G-TKIs) dasatinib and nilotinib
      produced historical rates of about 50% complete cytogenetic response (CCyR) and
      about 40% major molecular response (MMR) in chronic myeloid leukaemia (CML)
      patients failing imatinib. Direct comparisons between dasatinib and nilotinib are
      lacking, and few studies addressed the dynamics of deep molecular response (DMR)
      in a "real-life" setting. We retrospectively analyzed 163 patients receiving
      dasatinib (n = 95) or nilotinib (n = 68) as second-line therapy after imatinib.
      The two cohorts were comparable for disease's characteristics, although there was
      a higher rate of dasatinib use in imatinib-resistant and of nilotinib in
      intolerant patients. Overall, 75% patients not in CCyR and 60% patients not in
      MMR at 2G-TKI start attained this response. DMR was achieved by 61 patients
      (37.4%), with estimated rate of stable DMR at 5 years of 24%. After a median
      follow-up of 48 months, 60% of patients persisted on their second-line treatment.
      Rates and kinetics of cytogenetic and molecular responses, progression-free and
      overall survival were similar for dasatinib and nilotinib. In a "real-life"
      setting, dasatinib and nilotinib resulted equally effective and safe after
      imatinib failure, determining high rates of CCyR and MMR, and a significant
      chance of stable DMR, a prerequisite for treatment discontinuation.

PMID- 29581840
TI  - Interferon beta induces apoptosis in nasopharyngeal carcinoma cells via the TRAIL
      signaling pathway.
AB  - The combination of neoadjuvant chemotherapy, radiochemotherapy, and maintenance
      therapy with interferon beta (IFNbeta) has led to superior results in the
      treatment of children and adolescents with nasopharyngeal carcinoma (NPC).
      However, nothing is known about the mechanism of the antitumor activity of
      IFNbeta in NPC. Here, we investigate the role of IFNbeta on apoptosis in NPC
      cells. Six NPC cell lines, one patient-derived NPC xenograft (PDX) and one SV40
      transformed nasoepithelial cell line were used. Induction of apoptosis by IFNbeta
      was measured by flow cytometric analysis of subG1-DNA-content, Hoechst 33258
      staining and activation of caspase-3. Dissection of death ligand signaling
      pathways included measuring surface expression of its components by flow
      cytometry, activation by death ligands and neutralization with specific
      antibodies and siRNA. IFNbeta induced apoptosis at concentrations achievable in
      humans in five of six NPC cell lines and in PDX cells but not in nasoepithelial
      cells. Inhibition of caspases-3 and -8 abrogated this effect suggesting IFNbeta
      promoted apoptosis through the extrinsic pathway. IFNbeta induced surface
      expression of TRAIL and TRAIL-R2 and the addition of an anti-TRAIL-antibody or
      transfection with TRAIL-siRNA blocked IFNbeta-induced apoptosis. No induction of
      TRAIL-expression was noted in the IFNbeta-resistant cell line. In conclusion,
      IFNbeta leads to apoptosis in NPC cells in an autocrine way via the induction of
      TRAIL expression and subsequent activation of the TRAIL-signaling pathway. The
      mechanism described could at least partly explain the clinical benefit of IFNbeta
      in the treatment of NPC. Further studies in a mouse-xenograft model are warranted
      to substantiate this effect in vivo.

PMID- 29581841
TI  - Dysregulation of fibulin-5 and matrix metalloproteases in epithelial ovarian
      cancer.
AB  - Fibulin 5 (FBLN5) is an extracellular matrix glycoprotein that suppresses matrix
      metalloprotease 9 (MMP-9), angiogenesis and epithelial cell motility. Here, we
      investigated the regulation and function of FBLN5 in epithelial ovarian cancer
      (EOC). FBLN5 mRNA was down-regulated 5-fold in EOC relative to benign ovary. Not
      surprisingly, MMP9 mRNA and enzyme activity were increased significantly, and
      inversely correlated with FBLN5 gene expression. FBLN5 degradation products of
      52.8 and 41.3 kDa were increased substantially in EOC. We identified two
      candidate proteases (serine elastase and MMP-7, but not MMP-9) that cleave FBLN5.
      MMP-7, but not neutrophil elastase, gene expression was increased dramatically in
      EOC. Recombinant FBLN5 significantly inhibited adhesion of EOC cells to both
      laminin and collagen I. Finally, using immunohistochemistry, we found
      immunoreactive FBLN5 within tumor macrophages throughout human EOC tumors. This
      work indicates that FBLN5 is degraded in EOC most likely by proteases enriched in
      macrophages of the tumor microenvironment. Proteolysis of FBLN5 serves as a
      mechanism to promote cell adhesion and local metastasis of ovarian cancer cells.
      Promotion of a stable ECM with intact FBLN5 in the tumor matrix may serve as a
      novel therapeutic adjunct to prevent spread of ovarian cancer.

PMID- 29581842
TI  - Integrative proteomic and transcriptomic analysis provides evidence for TrkB
      (NTRK2) as a therapeutic target in combination with tyrosine kinase inhibitors
      for non-small cell lung cancer.
AB  - While several molecular targets have been identified for adenocarcinoma (ACA) of
      the lung, similar drivers with squamous cell carcinoma (SCC) are sparse. We
      compared signaling pathways and potential therapeutic targets in lung SCC and ACA
      tumors using reverse phase proteomic arrays (RPPA) from two independent cohorts
      of resected early stage NSCLC patients: a testing set using an MDACC cohort
      (N=140) and a validation set using the Cancer Genome Atlas (TCGA) cohorts. We
      identified multiple potentially targetable proteins upregulated in SCC, including
      NRF2, Keap1, PARP, TrkB, and Chk2. Of these potential targets, we found that TrkB
      also had significant increases in gene expression in SCC as compared to
      adenocarcinoma. Thus, we next validated the upregulation of TrkB both in vitro
      and in vivo and found that it was constitutively expressed at high levels in a
      subset of SCC cell lines. Furthermore, we found that TrkB inhibition suppressed
      tumor growth, invasiveness and sensitized SCC cells to tyrosine kinase EGFR
      inhibition in a cell-specific manner.

PMID- 29581843
TI  - Comparative study of interhemispheric functional connectivity in left eye
      monocular blindness versus right eye monocular blindness: a resting-state
      functional MRI study.
AB  - Objective: In the present study, we investigated the brain interhemispheric
      functional connectivity changes in left eye MB versus right eye MB patients by
      voxel-mirrored homotopic connectivity (VMHC) methods. Methods: A total of 31
      patients with MB (15 with left eye MB and 16 with right eye MB), and 31 healthy
      controls (HCs) closely matched for age were recruited. All subjects underwent
      functional magnetic resonance imaging (fMRI) examinations. The VMHC method was
      used to evaluate directly functional interactions between the hemispheres. A one
      way ANOVA was performed to determine the regions in which the VMHC differs
      between the three groups. Patients with MB were distinguished from HCs by a
      receiver operating characteristic (ROC) curve. The relationships between the mean
      VMHC signal values in many brain regions and clinical features in MB patients
      were calculated by pearson correlation analysis. Results: Compared with HCs, MB
      patients had significantly decreased VMHC values in the cuneus/calcarine/lingual
      gyrus. Furthermore, left eye MB showed decreased VMHC values in the
      cuneus/calcarine/lingual gyrus and showed increased VMHC values in the insula and
      middle frontal gyrus compared with HC. In addition, right eye MB showed decreased
      VMHC values in the cuneus/calcarine/lingual gyrus, primary motor cortex
      (M1)/primary somatosensory cortex (S1) and superior parietal lobule. Conclusion:
      MB subjects showed abnormal brain interhemispheric functional connectivity in
      visual pathways. Furthermore, different patterns of brain interhemispheric
      functional connectivity occurred in the left eye and right eye MB. These VMHC
      values provide much useful information to explain the neural mechanism changes in
      MB.

PMID- 29581844
TI  - Predictive value of inflammation-based prognostic scores in patients with
      metastatic renal cell carcinoma treated with cytoreductive nephrectomy.
AB  - Inflammation-based prognostic scores are useful for predicting survival in
      various cancers. Here, we aimed to determine the most useful inflammation-based
      prognostic score for predicting survival in patients with metastatic renal cell
      carcinoma undergoing cytoreductive nephrectomy. We retrospectively analyzed the
      data of 152 patients who underwent cytoreductive nephrectomy for metastatic renal
      cell carcinoma between 1986 and 2015. In the multivariate stepwise analysis, the
      combination of age, Memorial Sloan-Kettering Cancer Center score, histology,
      sarcomatoid change, clinical nodal stage, brain metastasis, and liver metastasis
      was a significant predictor for survival (Harrell's concordance index [c-index]:
      0.638). The c-index of the combination improved with the addition of an
      inflammation-based prognostic score: C-reactive protein (c-index: 0.672), Glasgow
      prognostic score (c-index: 0.674), neutrophil-to-lymphocyte ratio (c-index:
      0.685), lymphocyte-to-monocyte ratio (c-index: 0.670), platelet-to-lymphocyte
      ratio (c-index: 0.666), systemic inflammation response index (c-index: 0.652),
      and systemic immune-inflammation index (c-index: 0.678). The neutrophil-to
      lymphocyte ratio provided the greatest improvement in the c-index. Additional
      multivariate analysis showed that the neutrophil-to-lymphocyte ratio was an
      independent prognostic factor for survival (P < 0.0001). The neutrophil-to
      lymphocyte ratio was the most useful inflammation-based prognostic score for
      predicting survival in patients with metastatic renal cell carcinoma treated with
      cytoreductive nephrectomy.

PMID- 29581845
TI  - TP53 mutations and number of alterations correlate with maximum standardized
      uptake value (SUVmax) determined by positron emission tomography/computed
      tomography (PET/CT) [18F] fluorodeoxyglucose (18F-FDG PET).
AB  - Background: Our study explored the relationship between the molecular changes in
      cancer and the maximum standardized uptake value (SUVmax) determined by positron
      emission tomography/computed tomography (PET/CT) with [18F] fluorodeoxyglucose
      (18F-FDG). Results: A higher SUVmax correlated with TP53 alterations, but not
      with histologic diagnosis or other gene/pathway mutations or copy number
      alterations. In data from breast, lung and colon cancer, patients with the
      highest SUVmax show more genomic anomalies compared to those with the lowest
      SUVmax (P < 0.005). Conclusions: A higher SUVmax on 18F-FDG PET/CT is associated
      with TP53 tumor suppressor gene anomalies and the presence of more genomic
      anomalies. Since TP53 alterations and high SUVmax both correlate with a poor
      prognosis, the underlying mechanism/implications of this association merit
      further study. Methods: Overall, 176 patients with diverse cancers had a tumor
      biopsy within 6 months after a PET/CT image for SUVmax measurement. The biopsy
      was interrogated by next generation sequencing (182 to 315 genes). TP53, EGFR,
      ALK, MYC, MET and FGF/FGFR genes and DNA repair, PI3K/Akt/mTOR (PAM), MEK,
      CYCLIN, and WNT pathway genes were analyzed.

PMID- 29581846
TI  - Preclinical characterization of therapeutic antibodies targeted at the carboxy
      terminus of Sonic hedgehog.
AB  - The Sonic Hedgehog (Shh) signaling pathway has been implicated in the development
      and tumor progression of a number of human cancers. Using synthetic peptide
      mimics to mount an immune response, we generated a mouse mAb to the carboxy (C)
      terminus of the Shh protein and characterized its preclinical antitumor effects.
      In vitro screening guided selection of the best candidate for mAb scale-up
      production and therapeutic development. C-term anti-Shh, Ab 1C11-2G4 was selected
      based on ELISA screens, Western blotting, and flow cytometric analyses. Purified
      Ab 1C11-2G4 was shown to recognize and bind both Shh peptide mimics and cell
      surface Shh. Administration of Ab 1C11-2G4 not only reduced cell viability in 7
      cancer cell lines but also significantly inhibitted tumor growth in a xenograft
      model of A549 lung cancer cells. Ex vivo analyses of xenograft tumors revealed a
      reduction in Shh signal transduction and apoptosis in 2G4-treated mice.
      Collectively, our results provide early demonstration of the antitumor utility of
      antibodies specific for the C-terminal region of Shh, and support continued
      development to evaluate their potential efficacy in cancers in which Shh activity
      is elevated.

PMID- 29581847
TI  - Mandatory role of HMGA1 in human airway epithelial normal differentiation and
      post-injury regeneration.
AB  - Due to high levels of expression in aggressive tumors, high mobility group AT
      hook 1 (HMGA1) has recently attracted attention as a potential anti-tumor target.
      However, HMGA1 is also expressed in normal somatic progenitor cells, raising the
      question: how might systemic anti-HMGA1 therapies affect the structure and
      function of normal tissue differentiation? In the present study, RNA sequencing
      data demonstrated HMGA1 is highly expressed in human airway basal stem/progenitor
      cells (BC), but decreases with BC differentiation in air-liquid interface
      cultures (ALI). BC collected from nonsmokers, healthy smokers, and smokers with
      chronic obstructive pulmonary disease (COPD) displayed a range of HMGA1
      expression levels. Low initial expression levels of HMGA1 in BC were associated
      with decreased ability to maintain a differentiated ALI epithelium. HMGA1 down
      regulation in BC diminished BC proliferation, suppressed gene expression related
      to normal proliferation and differentiation, decreased airway epithelial
      resistance, suppressed junctional and cell polarity gene expression, and delayed
      wound closure of airway epithelium following injury. Furthermore, silencing of
      HMGA1 in airway BC in ALI increased the expression of genes associated with
      airway remodeling in COPD including squamous, epithelial-mesenchymal transition
      (EMT), and inflammatory genes. Together, the data suggests HMGA1 plays a central
      role in normal airway differentiation, and thus caution should be used to monitor
      airway epithelial structure and function in the context of systemic HMGA1
      targeted therapies.

PMID- 29581848
TI  - Aberrant expression of NKL homeobox gene HLX in Hodgkin lymphoma.
AB  - NKL homeobox genes are basic regulators of cell and tissue differentiation, many
      acting as oncogenes in T-cell leukemia. Recently, we described an hematopoietic
      NKL-code comprising six particular NKL homeobox genes expressed in hematopoietic
      stem cells and lymphoid progenitors, unmasking their physiological roles in the
      development of these cell types. Hodgkin lymphoma (HL) is a B-cell malignancy
      showing aberrant activity of several developmental genes resulting in disturbed B
      cell differentiation. To examine potential concordances in abnormal lymphoid
      differentiation of T- and B-cell malignancies we analyzed the expression of the
      hematopoietic NKL-code associated genes in HL, comprising HHEX, HLX, MSX1, NKX2
      3, NKX3-1 and NKX6-3. Our approach revealed aberrant HLX activity in 8 % of
      classical HL patients and additionally in HL cell line L-540. Accordingly, to
      identify upstream regulators and downstream target genes of HLX we used L-540
      cells as a model and performed chromosome and genome analyses, comparative
      expression profiling and functional assays via knockdown and overexpression
      experiments therein. These investigations excluded chromosomal rearrangements of
      the HLX locus at 1q41 and demonstrated that STAT3 operated directly as
      transcriptional activator of the HLX gene. Moreover, subcellular analyses showed
      highly enriched STAT3 protein in the nucleus of L-540 cells which underwent
      cytoplasmic translocation by repressing deacetylation. Finally, HLX inhibited
      transcription of B-cell differentiation factors MSX1, BCL11A and SPIB and of pro
      apoptotic factor BCL2L11/BIM, thereby suppressing Etoposide-induced cell death.
      Collectively, we propose that aberrantly expressed NKL homeobox gene HLX is part
      of a pathological gene network in HL, driving deregulated B-cell differentiation
      and survival.

PMID- 29581849
TI  - Urinary cell-free nucleic acid IQGAP3: a new non-invasive diagnostic marker for
      bladder cancer.
AB  - Background: There is growing interest in developing new non-invasive diagnostic
      tools for bladder cancer (BC) that have better sensitivity and specificity than
      cystoscopy and cytology. This study examined the value of urinary cell-free
      nucleic acid (NA) as a diagnostic marker for BC. Material and methods: A total of
      81 patients (74 BC and 7 normal controls) were used for a tissue set, and 212
      patients (92 BC and 120 normal controls) were used as a urine set. Expression of
      tissue mRNA and urinary cell-free NAs was then examined. Results: Four candidate
      genes were top-ranked in the tissue microarray. Expression levels of two of these
      (IQGAP3 and TOP2A) in BC tissue and urine samples from BC patients were
      significantly higher than those in samples from the control groups. Binary
      logistic regression analysis of cell-free NA levels in urine samples revealed
      that IQGAP3 was significantly associated with BC: PicoGreen-adjusted odds ratio
      (OR), 3.434; confidence interval (CI), 2.999-4.180; P<0.001; RiboGreen-adjusted
      OR, 2.242; CI, 1.793-2.840; P<0.001. Further analysis of IQGAP3 urinary cell-free
      NAs with respect to tumor invasiveness and grade also yielded a high AUC,
      suggesting that IQGAP3 can discriminate between BC patients and non-cancer
      patients with hematuria. Conclusions: Levels of IQGAP3 urinary cell-free NA in BC
      patients were significantly higher than those in normal controls or patients with
      hematuria. High levels of IQGAP3 urinary cell-free NA also reflected high
      expression in BC tissues. Therefore, IQGAP3 urinary cell-free NA may be a
      complementary diagnostic biomarker for BC.

PMID- 29581850
TI  - Interactome analysis of transforming growth factor-beta-activated kinase 1 in
      Helicobacter pylori-infected cells revealed novel regulators tripartite motif 28
      and CDC37.
AB  - Transforming growth factor-beta (TGFbeta)-activated kinase 1 (TAK1) plays a
      central role in controlling the cellular pro-inflammatory response via the
      activation of the nuclear factor kappaB (NF-kappaB)- and mitogen-activated
      protein (MAP) kinases-dependent transcriptional programs. Here, we show that
      depletion of TAK1 and the TAK1-binding proteins TAB1 and TAB2 affects NF-kappaB,
      JNK and p38 phosphorylation and suppresses NF-kappaB activity in AGS cells
      infected with Helicobacter pylori or stimulated with the cytokines TNF and IL
      1beta. To increase our understanding of TAK1 regulation and function, we
      performed mass spectrometry (MS)-based TAK1 interactomics. In addition to the
      identification of known and novel TAK1 interacting proteins, including TRIM28,
      CDC37 and STOML2, analysis of the MS data revealed various post-translational
      modifications within the TAK1/TAB complex. By applying siRNAs, TRIM28 and CDC37
      were found to regulate phosphorylations of TAK1, IkappaB kinases IKKalpha/IKKbeta
      and MAP kinases, NF-kappaB transactivation activity and IL-8 expression in the
      infected epithelial cells.

PMID- 29581851
TI  - MiR-124 aggravates failing hearts by suppressing CD151-facilitated angiogenesis
      in heart.
AB  - Heart failure (HF) is the final common pathway of various cardiovascular
      diseases. Although it is well documented that reduction of cardiac angiogenesis
      contributes to the progression from adaptive cardiac hypertrophy to HF, the
      molecular mechanisms remain unknown. In the present study, we found that cardiac
      expression of miR-124 was increased in patients and mice with HF. Recombinant
      adeno-associated virus (rAAV)-mediated miR-124 over-expression aggravated
      angiotensin II (Ang II) infusion-induced cardiac dysfunction and abnormal cardiac
      angiogenesis in mice. In vitro, transfection of miR-124 mimics significantly
      promoted apoptosis and reduced viability, migration, tube formation, and nitric
      oxide release in endothelial cells. In addition, CD151 was identified as a direct
      target of miR-124. Endothelial cell injury caused by CD151 silencing was mimicked
      by miR-124 over-expression. Re-expression of CD151 attenuated miR-124-mediated
      suppression of cardiac angiogenesis and cardiac dysfunction in Ang II-treated
      mice. Our observations suggest that miR-124 is an important negative regulator of
      cardiac angiogenesis and cardiac function, likely by suppressing the expression
      of CD151 in heart cells. Modulation of miR-124 levels may provide new strategies
      and targets for HF therapy.

PMID- 29581852
TI  - RhoA/Rho-kinase triggers epithelial-mesenchymal transition in mesothelial cells
      and contributes to the pathogenesis of dialysis-related peritoneal fibrosis.
AB  - Peritoneal fibrosis (PF) with associated peritoneal dysfunction is almost
      invariably observed in long-term peritoneal dialysis (PD) patients. Advanced
      glycation end products (AGEs) are pro-oxidant compounds produced in excess during
      the metabolism of glucose and are present in high levels in standard PD
      solutions. The GTPase RhoA has been implicated in PF, but its specific role
      remains poorly understood. Here, we studied the effects of RhoA/Rho-kinase
      signaling in AGEs-induced epithelial-mesenchymal transition (EMT) in human
      peritoneal mesothelial cells (HPMCs), and evaluated morphological and molecular
      changes in a rat model of PD-related PF. Activation of RhoA/Rho-kinase and
      activating protein-1 (AP-1) was assessed in HPMCs using pull-down and
      electrophoretic mobility shift assays, respectively, while expression of
      transforming growth factor-beta, fibronectin, alpha-smooth muscle actin,
      vimentin, N-cadherin, and E-cadherin expression was assessed using
      immunohistochemistry and western blot. AGEs exposure activated Rho/Rho-kinase in
      HPMCs and upregulated EMT-related genes via AP-1. These changes were prevented by
      the Rho-kinase inhibitors fasudil and Y-27632, and by the AP-1 inhibitor
      curcumin. Importantly, fasudil normalized histopathological and molecular
      alterations and preserved peritoneal function in rats. These data support the
      therapeutic potential of Rho-kinase inhibitors in PD-related PF.

PMID- 29581853
TI  - The protective autophagy activated by GANT-61 in MYCN amplified neuroblastoma
      cells is mediated by PERK.
AB  - The proto-oncogene MYC can trigger the unfolded protein response (UPR). The
      double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase
      (PERK), one of three primary branches of the UPR, is a key regulator of
      autophagy, promoting tumorigenesis. Upon activation of PERK, there is an increase
      in phosphorylation of the eukaryotic initiation factor-2 alpha (eIF2alpha), which
      in turn, activates the transcription factor-4 (ATF4), responsible for an
      increased expression of LC3, a common autophagy marker. PERK is repressed upon
      GLI1 and GLI2 induction. GANT-61 is an inhibitor of GLI1 and GLI2, known to
      reduce autophagy in MYCN non-amplified, but not in MYCN amplified neuroblastoma
      (NB) cells. In our study, we tested the effect of the joint administration of a
      PERK inhibitor (GSK2606414) and the GLI inhibitor GANT-61 to MYCN amplified and
      MYCN non-amplified NB cells. Our results suggest that inhibition of PERK impairs
      GANT-61 induced autophagy in NB cells with MYCN amplification, but had no effect
      on the MYCN non-amplified NB cells. In summary, PERK seems to be a good
      therapeutic target for NB. Inhibition of PERK reduces autophagy in MYCN amplified
      NB cells, thus amplifying the efficacy of the GLI inhibitor GANT-61 in reducing
      proliferation of this type of cancer cells.

PMID- 29581854
TI  - IRE1alpha-XBP1 inhibitors exerted anti-tumor activities in Ewing's sarcoma.
AB  - Ewing's sarcoma (ES) is the second-most frequent pediatric bone tumor.
      Chromosomal translocation t(11;22)(q24:q12) results in the formation of EWS/FLI1
      gene fusion, which is detected in approximately 90% of tumors of the Ewing
      family. Several transcriptome studies have provided lists of genes associated
      with EWS/FLI1 expression. However, the protein expression profiles associated
      with EWS/FLI1 have yet to be elucidated. In this study, to identify the regulated
      proteins associated with EWS/FLI1 and therapeutic targets in ES, we conducted
      proteomic studies using EWS/FLI1 knockdown in four Ewing's sarcoma cell lines and
      human mesenchymal stem cells (hMSCs) expressing EWS/FLI1. Isobaric tags for
      relative and absolute quantitation (i-TRAQ) analyses identified more than 2,000
      proteins regulated by the EWS/FLI1 fusion. In addition, the network analyses
      identified several critical pathways, including XBP1, which was ranked the
      highest. XBP1 is a protein well known to play an important role in the unfolded
      protein response (UPR) to endoplasmic reticulum (ER) stress through the IRE1alpha
      XBP1 pathway. We confirmed the high mRNA expression of XBP1 (spliced XBP1 and
      unspliced XBPl) in surgical samples and cell lines in ES. The silencing of XBP1
      significantly suppressed the cell viabilities in ES cell lines. In the inhibitor
      assays using IRE1alpha-XBP1 inhibitors, including toyocamycin, we confirmed that
      these agents significantly suppressed the cell viabilities, leading to apoptosis
      in ES cells both in vitro and in vivo. Our findings suggested that IRE1alpha-XBP1
      inhibitors might be useful for developing novel therapeutic strategies in ES.

PMID- 29581855
TI  - Association between angiotensin II receptor type 1 A1166C polymorphism and
      chronic kidney disease.
AB  - Studies of the association between angiotensin II receptor type 1 A1166C (AGTR1
      A1166C) polymorphism and chronic kidney disease (CKD) risk have yielded
      conflicting results. We conducted a combined case-control study and meta-analysis
      to better define this association. The case-control study included 634 end-stage
      renal disease (ESRD) patients and 739 healthy controls. AGTR1 A1166C genotype was
      determined using polymerase chain reaction and iPLEX Gold SNP genotyping methods.
      The meta-analysis included 24 studies found in the PubMed and Cochrane Library
      databases. Together, the case-control study and meta-analysis included 36
      populations (7,918 cases and 6,905 controls). We found no association between the
      C allele and ESRD (case-control study: OR: 1.02, 95% CI: 0.77-1.37; meta
      analysis: OR: 1.07; 95% CI: 0.97-1.18). Co-dominant, dominant, and recessive
      model results were also not significant. No known environmental factors moderated
      the effect of AGTR1 A1166C on CKD in our gene-environment interaction analysis.
      Sensitivity analysis showed an AGTR1 A1166C-CKD association in Indian populations
      (OR: 1.46, 95% CI: 1.26-1.69), but not in East Asian or Caucasian populations.
      Additional South Asian studies will be required to confirm the potential role of
      this polymorphism in CKD.

PMID- 29581856
TI  - Fibroblast growth factor receptor signaling plays a key role in transformation
      induced by the TMPRSS2/ERG fusion gene and decreased PTEN.
AB  - Prostate cancer is the most common visceral malignancy and the second leading
      cause of cancer deaths in US men. Correlative studies in human prostate cancers
      reveal a frequent association of the TMPRSS2/ERG (TE) fusion gene with loss of
      PTEN and studies in mouse models reveal that ERG expression and PTEN loss
      synergistically promote prostate cancer progression. To determine the mechanism
      by which ERG overexpression and PTEN loss leads to transformation, we
      overexpressed the TE fusion gene and knocked down PTEN in an immortalized but non
      transformed prostate epithelial cell line. We show that ERG overexpression in
      combination with PTEN loss can transform these immortalized but non-tumorigenic
      cells, while either alteration alone was not sufficient to fully transform these
      cells. Expression microarray analysis revealed extensive changes in gene
      expression in cells expressing the TE fusion with loss of PTEN. Among these gene
      expression changes was increased expression of multiple FGF ligands and
      receptors. We show that activation of fibroblast growth factor receptor signaling
      plays a key role in transformation induced by TE fusion gene expression in
      association with PTEN loss. In addition, in vitro and in silico analysis reveals
      PTEN loss is associated with widespread increases in FGF ligands and receptors in
      prostate cancer. Inhibitors of FGF receptor signaling are currently entering the
      clinic and our results suggests that FGF receptor signaling is a therapeutic
      target in cancers with TE fusion gene expression and PTEN loss.

PMID- 29581857
TI  - Trends in the prevalence of congenital hydrocephalus in 14 cities in Liaoning
      province, China from 2006 to 2015 in a population-based birth defect registry
      from the Liaoning Women and Children's Health Hospital.
AB  - The aim of this study was to assess the prevalence and trends of congenital
      hydrocephalus (CH) using a large population-based sample with cases retrieved
      from the Liaoning Birth Defects Registry, which included 14 cities, over a 10
      year period. CH prevalence, percent change, average change, and contribution
      rates of each city were calculated. Statistical analysis was performed using a
      Poisson regression model. There was a total of 3008 CH cases among 3,248,954 live
      births during the observational period (9.26 cases/10,000 live births). On
      average, the prevalence of CH had significantly decreased by 11.84% each year (P
      < 0.01). The three leading cities with the highest prevalence of CH were Chaoyang
      (13.73/10,000), Huludao (13.18/10,000), and Fuxin (12.71/10,000), while Yingkou
      (6.06/10,000), Dalian (6.27/10,000), and Anshan (6.56/10,000) had the lowest
      prevalence. Notably, significantly decreasing trends were observed in 10 (71.4%)
      of these 14 cities. In addition, the cities of Fushun, Shenyang, and Dalian had
      contributed to more than one-third of the decreasing trend in Liaoning province.
      In conclusion, this study provides evidence of the decreasing prevalence of CH
      over a 10-year period (2006-2015) in Liaoning province. Preventative efforts
      should be strengthened to further reduce the risk of CH in these high prevalence
      areas.

PMID- 29581858
TI  - Depleting ovarian cancer stem cells with calcitriol.
AB  - Cancer stem cells (CSCs) represent the root of many solid tumors including
      ovarian cancer. Eradication of CSCs represents a novel cancer therapeutic
      strategy. Calcitriol, also known as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is an
      active metabolite of vitamin D, functioning as a potent steroid hormone.
      Calcitriol has shown anti-tumor effects in various cancers by regulating multiple
      signaling pathways. It has been reported that calcitriol can regulate the
      properties of normal and CSCs. However, the effect of calcitriol on the ovarian
      cancer growth and ovarian CSCs is still unclear. Here, by using a mouse
      subcutaneous xenograft model generated with human ovarian cancer cells, we have
      demonstrated that administration of calcitriol is able to strikingly delay the
      tumor growth. Calcitriol treatment can also deplete the ovarian CSC population
      characterized by ALDH+ and CD44+CD117+; decrease their capacity to form sphere
      under the CSC culture condition, and reduce the frequency of tumor-initiating
      cells, as evaluated by in vivo limiting dilution analysis. Mechanistic
      investigation revealed that calcitriol depletes CSCs via the nuclear vitamin D
      receptor (VDR)-mediated inhibition of the Wnt pathway. Furthermore, the
      activation of VDR pathway is more sensitive to calcitriol in ovarian CSCs than in
      non-CSCs, although the expression levels of VDR are comparable. Taken together,
      our data indicate that calcitriol is able to deplete the ovarian CSC population
      by inhibiting their Wnt signaling pathway, consequently, impeding the growth of
      xenograft tumors.

PMID- 29581859
TI  - A pilot study on primary cultures of human respiratory tract epithelial cells to
      predict patients' responses to H7N9 infection.
AB  - Avian influenza A(H7N9) virus infections frequently lead to acute respiratory
      distress syndrome and death in humans. We aimed to investigate whether primary
      cultures of human respiratory tract epithelial cells are helpful to understand
      H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related
      characteristics can affect the host's response to infection. Normal human
      bronchial epithelial cells (isolated from two different donors) and primary
      epithelial cells (harvested from 27 patients undergoing airway surgery) were
      experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection,
      the culture media were collected for viral RNA quantitation and cytokine
      detection. Both H7N9 and H1N1pdm viruses replicated and induced a cytokine
      response differently for each donor in the normal human bronchial epithelial
      model. H7N9 replicated equivalently in epithelial cells harvested from the
      inferior turbinate and paranasal sinus, and those from the larynx and bronchus,
      at 72 h post-infection. Viral RNA quantity at 72 h was significantly higher in
      patients aged 21-64 years than in patients aged >= 65 years; however, no effects
      of sex, medical comorbidities, and obesity were noted. H7N9-infected cultured
      cells released multiple cytokines within 72 h. Levels of interleukin-1beta,
      interleukin-6, interleukin-8, interferon-gamma, and tumor necrosis factor-alpha
      were associated differently with patient-related characteristics (such as age,
      sex, obesity, and medical comorbidities). In the era of precision medicine, these
      findings illustrate the potential utility of this primary culture approach to
      predict a host's response to H7N9 infection or to future infection by newly
      emerging viral infections, and to dissect viral pathogenesis.

PMID- 29581860
TI  - Novel natural withanolides induce apoptosis and inhibit migration of
      neuroblastoma cells through down regulation of N-myc and suppression of
      Akt/mTOR/NF-kappaB activation.
AB  - Despite recent advances in intensive chemotherapy treatments, long-term success
      is achieved in less than 30% of children with high-risk neuroblastoma (NB). Key
      regulatory pathways including the PI3K/Akt, mTOR and NF-kappaB are implicated in
      the pathogenesis of NB. Although drugs targeting these individual pathways are in
      clinical trials, they are not effective due to the activation of compensatory
      mechanisms. We have previously reported that natural novel withanolides from
      Physalis longifolia can potently inhibit these key regulatory pathways
      simultaneously. In the present study, we examined the efficacy and mechanisms
      through which novel withanolides and their acetate derivatives (WGA-TA and WGB
      DA) from P.longifolia kill NB cells. The results from the study demonstrated that
      our novel acetate derivatives are highly effective in inhibiting the
      proliferation, shifting the cell cycle and inducing apoptosis in a dose dependent
      manner. Analysis of oncogenic pathway proteins targeted by withanolides indicated
      induction of heat shock response due to oxidative stress. Dose dependent decrease
      in clients of HSP90 chaperone function due to suppression of Akt, mTOR, and NF
      kappaB pathways led to decrease in the expressions of target genes such as cyclin
      D1, N-myc and Survivin. Additionally, there was a dose dependent attenuation of
      the migration and invasion of NB cells. Furthermore, the lead compound WGA-TA
      showed significant reduction in tumor growth of NB xenografts. Taken together,
      these results suggest that withanolides are an effective therapeutic option
      against NBs.

PMID- 29581861
TI  - The circadian clock regulates cisplatin-induced toxicity and tumor regression in
      melanoma mouse and human models.
AB  - Cisplatin is one of the most commonly used chemotherapeutic drugs; however,
      toxicity and tumor resistance limit its use. Studies using murine models and
      human subjects have shown that the time of day of cisplatin treatment influences
      renal and blood toxicities. We hypothesized that the mechanisms responsible for
      these outcomes are driven by the circadian clock. We conducted experiments using
      wild-type and circadian disrupted Per1/2-/- mice treated with cisplatin at
      selected morning (AM) and evening (PM) times. Wild-type mice treated in the
      evening showed an enhanced rate of removal of cisplatin-DNA adducts and less
      toxicity than the morning-treated mice. This temporal variation in toxicity was
      lost in the Per1/2-/- clock-disrupted mice, suggesting that the time-of-day
      effect is linked to the circadian clock. Observations in blood cells from humans
      subjected to simulated day and night shift schedules corroborated this view.
      Per1/2-/- mice also exhibited a more robust immune response and slower tumor
      growth rate, indicating that the circadian clock also influences the immune
      response to melanoma tumors. Our findings indicate that cisplatin
      chronopharmacology involves the circadian clock control of DNA repair as well as
      immune responses, and thus affects both cisplatin toxicity and tumor growth. This
      has important implications for chronochemotherapy in cancer patients, and also
      suggests that influencing the circadian clock (e.g., through bright light
      treatment) may be explored as a tool to improve patient outcomes.

PMID- 29581862
TI  - Doxorubicin-induced loss of DNA topoisomerase II and DNMT1- dependent suppression
      of MiR-125b induces chemoresistance in ALK-positive cells.
AB  - Systemic anaplastic large-cell lymphoma (ALCL) is a childhood T cell neoplasm
      defined by the presence or absence of translocations that lead to the ectopic
      expression of anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK)
      fusions being the most common. Polychemotherapy involving doxorubicin is the
      standard first-line treatment but for the 25 to 35% of patients who relapse and
      develop resistance the prognosis remains poor. We studied the potential role of
      the microRNA miR-125b in the development of resistance to doxorubicin in NPM
      ALK(+) ALCL. Our results show that miR-125b expression is repressed in NPM-ALK(+)
      cell lines and patient samples through hypermethylation of its promoter. NPM-ALK
      activity, in cooperation with DNA topoisomerase II (Topo II) and DNA
      methyltransferase 1 (DNMT1), is responsible for miR-125b repression through DNA
      hypermethylation. MiR-125b repression was reversed by the inhibition of DNMTs
      with decitabine or the inhibition of DNA topoisomerase II with either doxorubicin
      or etoposide. In NPM-ALK(+) cell lines, doxorubicin treatment led to an increase
      in miR-125b levels by inhibiting the binding of DNMT1 to the MIR125B1 promoter
      and downregulating the pro-apoptotic miR-125b target BAK1. Reversal of miR-125b
      silencing, increased miR-125b levels and reduced BAK1 expression also led to a
      lower efficacy of doxorubicin, suggestive of a pharmacoresistance mechanism. In
      line with this, miR-125b repression and increased BAK1 expression correlated with
      early relapse in human NPM-ALK(+) ALCL primary biopsies. Collectively our
      findings suggest that miR-125b could be used to predict therapeutic outcome in
      NPM-ALK(+) ALCL.

PMID- 29581863
TI  - Reduced SMAD2/3 activation independently predicts increased depth of human
      cutaneous squamous cell carcinoma.
AB  - The incidence of cutaneous squamous cell carcinoma (cSCC) is rising. Whilst the
      majority are cured surgically, aggressive metastatic cSCC carry a poor prognosis.
      Inactivating mutations in transforming growth factor beta (TGF-beta) receptors
      have been identified amongst genetic drivers of sporadic tumours and murine
      models of cSCC, suggesting a tumour suppressor function for TGF-beta in normal
      skin. However, paradoxically, TGF-beta acts as a tumour promoter in some murine
      model systems. Few studies have analysed the role of TGF-beta/activin signalling
      in human normal skin, hyper-proliferative skin disorders and cSCC. Antibodies
      recognising phospho-SMAD proteins which are activated during canonical TGF
      beta/activin signalling were validated for use in immunohistochemistry. A tissue
      microarray comprising FFPE lesional and perilesional tissue from human primary
      invasive cSCC (n=238), cSCC in-situ (n=2) and keratocanthoma (n=9) were analysed
      in comparison with tissues from normal human scalp (n=10). Phosphorylated SMAD2
      and SMAD3 were detected in normal interfollicular epidermal keratinocytes and
      were also highly localised to inner root sheath, matrix cells and Keratin 15
      positive cells. Lesional cSCC tissue had significantly reduced activated SMAD2/3
      compared to perilesional tissue, consistent with a tumour suppressor role for
      SMAD2/3 activators in cSCC. Increased cSCC tumour thickness inversely correlated
      with the presence of phospho-SMADs in tumour tissue suggesting that a reduction
      in canonical TGF-beta/activin signalling may be associated with disease
      progression.

PMID- 29581864
TI  - Galectin-3 sensitized melanoma cell lines to vemurafenib (PLX4032) induced cell
      death through prevention of autophagy.
AB  - Melanoma is a current worldwide problem, as its incidence is increasing. In the
      last years, several studies have shown that melanoma cells display high levels of
      autophagy, a self-degradative process that can promote survival leading to drug
      resistance. Consequently, autophagy regulation represents a challenge for cancer
      therapy. Herein, we showed that galectin-3 (Gal-3), a beta-galactoside binding
      lectin which is often lost along melanoma progression, is a negative regulator of
      autophagy in melanoma cells. Our data demonstrated that Gal-3low/negative cells
      were more resistant to the inhibition of the activity of the cancer driver gene
      BRAFV600E by vemurafenib (PLX4032). Interestingly, in these cells, starvation
      caused further LC3-II accumulation in cells exposed to chloroquine, which
      inhibits the degradative step in autophagy. In addition, Gal-3 low/negative tumor
      cells accumulated more LC3-II than Gal-3 high tumor cells in vivo. Resistance of
      Gal-3low/negative cells was associated with increased production of superoxide
      and activation of the Endoplasmic Reticulum (ER) stress response, as evaluated by
      accumulation of GRP78. Pharmacological inhibition of autophagy with bafilomycin A
      reversed the relative resistance of Gal-3low/negative cells to vemurafenib
      treatment. Taken together, these results show that the autophagic flux is
      dependent on Gal-3 levels, which attenuate the prosurvival role of autophagy.

PMID- 29581865
TI  - Luminal breast cancer-specific circular RNAs uncovered by a novel tool for data
      analysis.
AB  - Circular RNAs are highly stable molecules present in all eukaryotes generated by
      distinct transcript processing. We have exploited poly(A-) RNA-Seq data generated
      in our lab in MCF-7 breast cancer cells to define a compilation of exonic
      circRNAs more comprehensive than previously existing lists. Development of a
      novel computational tool, named CircHunter, allowed us to more accurately
      characterize circRNAs and to quantitatively evaluate their expression in publicly
      available RNA-Seq data from breast cancer cell lines and tumor tissues. We
      observed and confirmed, by ChIP analysis, that exons involved in circularization
      events display significantly higher levels of the histone post-transcriptional
      modification H3K36me3 than non-circularizing exons. This result has potential
      impact on circRNA biogenesis since H3K36me3 has been involved in alternative
      splicing mechanisms. By analyzing an Ago-HITS-CLIP dataset we also found that
      circularizing exons overlapped with an unexpectedly higher number of Ago binding
      sites than non-circularizing exons. Finally, we observed that a subset of MCF-7
      circRNAs are specific to tumor versus normal tissue, while others can distinguish
      Luminal from other tumor subtypes, thus suggesting that circRNAs can be exploited
      as novel biomarkers and drug targets for breast cancer.

PMID- 29581866
TI  - Calpastatin phosphorylation regulates radiation-induced calpain activity in
      glioblastoma.
AB  - Glioblastoma (GBM) is an aggressive, malignant brain tumor that inevitably
      develops resistance to conventional chemotherapy and radiation treatments. In
      order to identify signaling pathways involved in the development of radiation
      resistance, we performed mass spectrometry-based phospho-proteomic profiling of
      GBM cell lines and normal human astrocytes before and after radiation treatment.
      We found radiation induced phosphorylation of a number of proteins including
      calpastatin, specifically in GBM stem cells (GSCs). Herein, we focused on
      calpastatin, an endogenous inhibitor of calpain proteases. Radiation-induced
      phosphorylation of calpastatin at Ser-633 within the inhibitory domain was
      validated with a phospho-specific antibody. In order to test the functional
      significance of phosphorylated calpastatin, we utilized site-directed mutagenesis
      to generate phospho-inactive (Ser633Ala) and phospho-mimetic (Ser633Glu) mutant
      calpastatin. GBM cell lines stably expressing the mutant calpastatin showed that
      phosphorylation was necessary for radiation-induced calpain activation. We also
      showed that casein kinase 2, a pro-survival kinase overexpressed in many cancer
      types, phosphorylated calpastatin at Ser-633. Our results indicate that
      calpastatin phosphorylation promotes radiation resistance in GBM cells by
      increasing the activity of calpain proteases, which are known to promote survival
      and invasion in cancer.

PMID- 29581867
TI  - Long noncoding RNA ANRIL as a novel biomarker of lymph node metastasis and
      prognosis in human cancer: a meta-analysis.
AB  - Dysregulation of the long noncoding RNA antisense noncoding RNA in the INK4 locus
      (ANRIL) has been reported in various solid tumors. We performed a synthetic
      analysis to clarify the clinical value of ANRIL as a prognostic indicator in
      malignant tumors. Article collection was conducted using several electronic
      databases, including PubMed, Web of Science, Medline, OVID and Embase (up to July
      14 2017). Thirteen original studies and 1172 total patients were included in the
      meta-analysis. There was a significant positive association between the high
      expression level of ANRIL and lymph node metastasis (OR = 4.77, 95% CI: 2.30
      9.91, P < 0.001) by a random effects model (I2 = 73.2, P = 0.001) and negative
      association with poor grade cancer (OR = 3.44, 95% CI: 1.68-7.08) by a random
      effects model (I2 = 77.9, P = 0.000). The results of the meta-analysis showed
      that overexpression of ANRIL is positively related to poor overall survival (OS)
      (pooled HR = 2.12, 95% CI: 1.78-2.53, P < 0.0001) by a fixed-effects model (I2 =
      0%, P = 0.654) and poor disease-free survival (DFS) (HR = 2.10, 95% CI: 1.51
      2.92, P < 0.001) by a fixed-effects model (I2 = 13.3%, P = 0.315) in human solid
      cancers. Statistically significant associations were also found with cancer type,
      analysis method, sample size, and follow-up time. In conclusion, ANRIL may serve
      as a novel biomarker for indicating lymph node metastasis and prognosis in human
      cancer.

PMID- 29581868
TI  - The efficacy and safety of paclitaxel and carboplatin with versus without
      bevacizumab in patients with non-small-cell lung cancer: a systematic review and
      meta-analysis.
AB  - Objectives: To investigate the efficacy and safety of Bevacizumab (Bev) used in
      combination with paclitaxel and carboplatin (PC), compared with PC alone in
      patients with advanced non-small-cell lung cancer (NSCLC). Materials and Methods:
      We searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials
      and Chinese Biomedical Literature electronic databases, to identify randomized
      controlled trials of PC plus Bev versus PC alone for the treatment of NSCLC. The
      meta-analysis was performed using Reviewer Manager Version 5.3 software provided
      by the Cochrane Collaboration. The primary endpoint was progression-free survival
      (PFS), and the secondary endpoints were overall survival (OS), objective response
      rate (ORR), the incidence of severe adverse events and treatment-related deaths.
      Results: The final analysis included 5 trials with a total of 1486 patients.
      Compared with PC alone, the regimen of PC plus Bev resulted in significantly
      longer PFS (HR = 0.57; 95% CI = 0.46 to 0.71; p < 0.00001), longer OS (HR = 0.81;
      95% CI = 0.71 to 0.92; p = 0.0009) and higher response rates (RR = 2.06; 95% CI =
      1.73 to 2.44; p < 0.00001). However, grade >= 3 neutropenia, haemoptysis,
      hypertension, proteinuria and bleeding events were more common among patients who
      received Bev, and these patients also experienced increased rates of treatment
      related death. Conclusions: Compared with PC alone, the combination of PC with
      Bev could prolong PFS, OS and RR for patients with advanced non-squamous NSCLC.
      However, this combination could lead to a higher toxicity profile. Therefore, the
      benefits and risks should be considered before making treatment decisions.

PMID- 29581869
TI  - Trigger pSA predicting recurrence from positive choline PET/CT with prostate
      cancer after initial treatment.
AB  - Purpose: To assess the relationship between the diagnostic accuracy of Choline
      positron emission tomography/computed tomography (PET/CT) and the trigger
      prostate-specific antigen (PSA) level in patients with a biochemical recurrence
      of prostate cancer. Materials and Methods: A meta-analysis was conducted to
      synthesize data across multiple studies. Results: The pooled sensitivity and
      specificity of choline PET/CT were 82% (95% Confidence Interval (CI):80-84%) and
      92% (95%CI: 90-93%), respectively. The pooled sensitivity and specificity of 18F
      choline PET/CT were 81% (95%CI: 78-84%) and 90% (95%CI: 85-93%), respectively.
      The pooled sensitivity and specificity of 11C-choline PET/CT were 83% (95% CI: 80
      86%) and 92% (95% CI: 90-94%), respectively. The pooled detection rate of 18F
      choline PET/CT and 11C-choline PET/CT were 58% (95% CI: 48-68%) and 58% (95%CI:
      49-68%), respectively. Conclusions: Trigger PSA is an important risk factor for
      positive findings of Choline PET/CT and the detection rate of Choline PET/CT for
      recurrent prostate cancer increased in parallel with raises in PSA-values.
      Choline PET/CT got higher detection rate while the trigger PSA > 2ng/ml.

PMID- 29581870
TI  - Clinicopathological and prognostic significance of Twist overexpression in NSCLC.
AB  - Several studies were conducted to explore the prognostic significance of Twist in
      non-small cell lung cancer (NSCLC), however, contradictory results in different
      studies were reported. To this end, we presented a systematic review aiming to
      summarize the prognostic significance of Twist in patients with NSCLC. 5 studies
      involving a total of 572 patients were identified. The result indicated that high
      Twist expression was significantly associated with a worse overall survival (OS)
      (hazard ratio (HR) = 2.19, 95% confidence interval (95% CI) = 1.64-2.94, p <
      0.001; I2 = 0.0%, fixed effect), recurrence-free survival (RFS) (HR = 2.476, 95%
      CI = 1.728-3.547, p < 0.001; I2 = 0.0%, fixed effect) and lymph node or other
      metastasis (odds rate (OR) = 0.419, 95% CI = 0.259-0.679, P < 0.001, fixed
      effect). Subgroup analysis revealed that the expression of Twist in Chinese
      patients might be more closely associated with the prognosis of NSCLC than in
      American patients. Overall, these results indicated that Twist over-expression in
      patients with NSCLC might be related to poor prognosis and serves as an
      unfavorable predictor of poor clinicopathological prognosis factor.

PMID- 29581871
TI  - Positive urinary fluorescence in situ hybridization indicates poor prognosis in
      patients with upper tract urothelial carcinoma.
AB  - Here, we evaluated the potential contribution of fluorescent in situ
      hybridization (FISH) as a prognostic risk factor of bladder recurrence and
      survival in patients with upper tract urothelial carcinoma (UTUC). A total of 159
      UTUC patients were enrolled in this study from January 2012 to May 2016. The 159
      voided urine samples before surgery were analyzed using the UroVysion(r) kit to
      detect the copy numbers of chromosomes 3, 7, 17 and 9p21 (p16). Patients were
      classified using an optimal cutoff value of chromosomes 3, 7, 17, and 9p21. Cox's
      proportional hazards regression model was used to assess the prognostic value of
      FISH for bladder recurrence and survival. We found that 27 (17.6%) patients
      experienced bladder recurrence and 26 (16.4%) patients died from cancer, with a
      median follow-up of 27 months. The patients with positive FISH result were more
      likely to present bladder recurrence (p = 0.077). However, positive FISH was not
      associated with cancer specific-free survival (CSS) (p = 0.944). Tumor
      multifocality, the percentage of abnormal chromosome 3 > 5%, chromosome 7 > 6%,
      chromosome 17 > 11% and deletion of p16 > 4% were significant prognostic risk
      factors for BRFS in univariate analysis. In multivariate analysis, only tumor
      multifocality (hazard ratio [HR] = 3.487, 95%CI: 1.605-7.576, p = 0.002) and the
      percentage of p16 loss > 4% were both prognostic risk factors for bladder
      recurrence (HR = 3.487, 95%CI: 1.605-7.576, p = 0.002). These data consider that
      the urinary FISH test could be a powerful tool in predicting the risk of bladder
      recurrence in patients with UTUC.

PMID- 29581872
TI  - Type 2 diabetes mellitus-related changes in left ventricular structure and
      function in patients with chronic kidney disease.
AB  - Type 2 Diabetes mellitus (DM) is the leading cause of chronic kidney disease
      (CKD) worldwide, and is associated with an increased risk of left ventricular
      (LV) hypertrophy, LV systolic and diastolic dysfunctions. The aim of this study
      was to investigate abnormal echocardiographic findings in patients with CKD with
      and without DM, and identify the factors associated with these abnormalities. We
      enrolled 356 pre-dialysis patients with CKD (stages 3-5), including 208 with DM
      and 148 without DM. The structure and systolic and diastolic functions of the
      left ventricle were assessed using echocardiography, and the clinical and
      echocardiographic parameters were analyzed. The patients with DM had higher rates
      of observed/predicted left ventricular mass > 128% (69.5% vs. 56.7%, p = 0.015),
      midwall fractional shortening < 14% (22.6% vs. 8.8%, p = 0.001), and ratio of
      peak early transmitral filling wave velocity to early diastolic velocity of
      lateral mitral annulus > 12 (32.7% vs. 16.2%, p < 0.001) than those without DM.
      Multivariate analysis showed that male sex, a history of smoking, high systolic
      blood pressure, high body mass index, high levels of fasting glucose and total
      cholesterol, low levels of albumin and hemoglobin, and a low estimated glomerular
      filtration rate were associated with abnormal echocardiographic findings. The
      rates of inappropriate left ventricular mass, systolic and diastolic dysfunction
      were higher in our patients with CKD and DM than in those without DM.

PMID- 29581873
TI  - Healthy efficacy of Nostoc commune Vaucher.
AB  - Nostoc commune Vaucher, a macroscopic cyanobacterium, has long been appreciated
      as a healthy food and traditional medicine worldwide. Accumulated evidence has
      demonstrated that it possesses a wide range of remarkably protective
      physiological and pharmacological activities, largely based on animal and in
      vitro studies. In this review, we summarise and update evidence regarding the
      chemical composition and nutritional characteristics of Nostoc commune Vaucher,
      and comprehensively discuss the recent studies on the antioxidative, anti
      inflammatory, anti-carcinogenic and immune regulation properties of Nostoc
      commune Vaucher and Nostoc commune Vaucher-derived extracts. The available
      results demonstrate the potential of it to act as a functional food for the
      amelioration of human associated diseases. More details from human clinical
      trials should be a matter of further investigation.

PMID- 29581874
TI  - Old Sonic Hedgehog, new tricks: a new paradigm in thoracic malignancies.
AB  - The Sonic Hedgehog (Shh) pathway is physiologically involved during
      embryogenesis, but is also activated in several diseases, including solid
      cancers. Previous studies have demonstrated that the Shh pathway is involved in
      oncogenesis, tumor progression and chemoresistance in lung cancer and
      mesothelioma. The Shh pathway is also closely associated with epithelial
      mesenchymal transition and cancer stem cells. Recent findings have revealed that
      a small proportion of lung cancer cells expressed an abnormal full-length Shh
      protein, associated with cancer stem cell features. In this paper, we review the
      role of the Shh pathway in thoracic cancers (small cell lung cancer, non-small
      cell lung cancer, and mesothelioma) and discuss the new perspectives of cancer
      research highlighted by the recent data of the literature.

PMID- 29581877
TI  - Immune checkpoint inhibitors in large cell neuroendocrine carcinoma: current
      status.
AB  - Introduction: Large cell neuroendocrine carcinomas (LCNEC) are a group of rare
      high grade neuroendocrine tumors that often behave clinically like small cell
      carcinoma (SCLC) and are treated as such. No major advancement in the management
      of these tumors has occurred in the last 30 years. Methods: We present a case
      series of three cases from Markey Cancer center along with a review of 13
      published cases in the literature wherein immune-checkpoint inhibitors were
      utilized in the management of LCNEC. Results: Immune-checkpoint inhibitors might
      have clinical activity in LCNEC. Conclusion: Role of immune-checkpoint inhibitors
      should be explored in prospective LCNEC clinical trials. We summarize current
      evidence regarding use of immune checkpoint inhibitors in the treatment of LCNEC.

PMID- 29581876
TI  - Prostatic cancers: understanding their molecular pathology and the 2016 WHO
      classification.
AB  - Accumulating evidence suggests that prostatic cancers represent a group of
      histologically and molecularly heterogeneous diseases with variable clinical
      courses. In accordance with the increased knowledge of their clinicopathologies
      and genetics, the World Health Organization (WHO) classification of prostatic
      cancers has been revised. Additionally, recent data on their comprehensive
      molecular characterization have increased our understanding of the genomic basis
      of prostatic cancers and enabled us to classify them into subtypes with distinct
      molecular pathologies and clinical features. Our increased understanding of the
      molecular pathologies of prostatic cancers has permitted their evolution from a
      poorly understood, heterogeneous group of diseases with variable clinical courses
      to characteristic molecular subtypes that allow the implementation of
      personalized therapies and better patient management. This review provides
      perspectives on the new 2016 WHO classification of prostatic cancers as well as
      recent knowledge of their molecular pathologies. The WHO classification of
      prostatic cancers will require additional revisions to allow for reliable and
      clinically meaningful cancer diagnoses as a better understanding of their
      molecular characteristics is obtained.

PMID- 29581878
TI  - The geometric preference subtype in ASD: identifying a consistent, early-emerging
      phenomenon through eye tracking.
AB  - Background: The wide range of ability and disability in ASD creates a need for
      tools that parse the phenotypic heterogeneity into meaningful subtypes. Using eye
      tracking, our past studies revealed that when presented with social and geometric
      images, a subset of ASD toddlers preferred viewing geometric images, and these
      toddlers also had greater symptom severity than ASD toddlers with greater social
      attention. This study tests whether this "GeoPref test" effect would generalize
      across different social stimuli. Methods: Two hundred and twenty-seven toddlers
      (76 ASD) watched a 90-s video, the Complex Social GeoPref test, of dynamic
      geometric images paired with social images of children interacting and moving.
      Proportion of visual fixation time and number of saccades per second to both
      images were calculated. To allow for cross-paradigm comparisons, a subset of 126
      toddlers also participated in the original GeoPref test. Measures of cognitive
      and social functioning (MSEL, ADOS, VABS) were collected and related to eye
      tracking data. To examine utility as a diagnostic indicator to detect ASD
      toddlers, validation statistics (e.g., sensitivity, specificity, ROC, AUC) were
      calculated for the Complex Social GeoPref test alone and when combined with the
      original GeoPref test. Results: ASD toddlers spent a significantly greater amount
      of time viewing geometric images than any other diagnostic group. Fixation
      patterns from ASD toddlers who participated in both tests revealed a significant
      correlation, supporting the idea that these tests identify a phenotypically
      meaningful ASD subgroup. Combined use of both original and Complex Social GeoPref
      tests identified a subgroup of about 1 in 3 ASD toddlers from the "GeoPref"
      subtype (sensitivity 35%, specificity 94%, AUC 0.75.) Replicating our previous
      studies, more time looking at geometric images was associated with significantly
      greater ADOS symptom severity. Conclusions: Regardless of the complexity of the
      social images used (low in the original GeoPref test vs high in the new Complex
      Social GeoPref test), eye tracking of toddlers can accurately identify a specific
      ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are
      predictive of ASD at the individual subject level and thus potentially useful for
      various clinical applications (e.g., early identification, prognosis, or
      development of subtype-specific treatments).

PMID- 29581875
TI  - Vive la radioresistance!: converging research in radiobiology and biogerontology
      to enhance human radioresistance for deep space exploration and colonization.
AB  - While many efforts have been made to pave the way toward human space
      colonization, little consideration has been given to the methods of protecting
      spacefarers against harsh cosmic and local radioactive environments and the high
      costs associated with protection from the deleterious physiological effects of
      exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the
      foundations of a roadmap toward enhancing human radioresistance for the purposes
      of deep space colonization and exploration. We outline future research directions
      toward the goal of enhancing human radioresistance, including upregulation of
      endogenous repair and radioprotective mechanisms, possible leeways into gene
      therapy in order to enhance radioresistance via the translation of exogenous and
      engineered DNA repair and radioprotective mechanisms, the substitution of organic
      molecules with fortified isoforms, and methods of slowing metabolic activity
      while preserving cognitive function. We conclude by presenting the known
      associations between radioresistance and longevity, and articulating the position
      that enhancing human radioresistance is likely to extend the healthspan of human
      spacefarers as well.

PMID- 29581879
TI  - Transport of charged small molecules after electropermeabilization - drift and
      diffusion.
AB  - Background: Applications of electric-field-induced permeabilization of cells
      range from cancer therapy to wastewater treatment. A unified understanding of the
      underlying mechanisms of membrane electropermeabilization, however, has not been
      achieved. Protocols are empirical, and models are descriptive rather than
      predictive, which hampers the optimization and expansion of electroporation-based
      technologies. A common feature of existing models is the assumption that the
      permeabilized membrane is passive, and that transport through it is entirely
      diffusive. To demonstrate the necessity to go beyond that assumption, we present
      here a quantitative analysis of the post-permeabilization transport of three
      small molecules commonly used in electroporation research - YO-PRO-1, propidium,
      and calcein - after exposure of cells to minimally perturbing, 6 ns electric
      pulses. Results: Influx of YO-PRO-1 from the external medium into the cell
      exceeds that of propidium, consistent with many published studies. Both are much
      greater than the influx of calcein. In contrast, the normalized molar efflux of
      calcein from pre-loaded cells into the medium after electropermeabilization is
      roughly equivalent to the influx of YO-PRO-1 and propidium. These relative
      transport rates are correlated not with molecular size or cross-section, but
      rather with molecular charge polarity. Conclusions: This comparison of the
      kinetics of molecular transport of three small, charged molecules across
      electropermeabilized cell membranes reveals a component of the mechanism of
      electroporation that is customarily taken into account only for the time during
      electric pulse delivery. The large differences between the influx rates of
      propidium and YO-PRO-1 (cations) and calcein (anion), and between the influx and
      efflux of calcein, suggest a significant role for the post-pulse transmembrane
      potential in the migration of ions and charged small molecules across
      permeabilized cell membranes, which has been largely neglected in models of
      electroporation.

PMID- 29581880
TI  - Imputation from SNP chip to sequence: a case study in a Chinese indigenous
      chicken population.
AB  - Background: Genome-wide association studies and genomic predictions are thought
      to be optimized by using whole-genome sequence (WGS) data. However, sequencing
      thousands of individuals of interest is expensive. Imputation from SNP panels to
      WGS data is an attractive and less expensive approach to obtain WGS data. The
      aims of this study were to investigate the accuracy of imputation and to provide
      insight into the design and execution of genotype imputation. Results: We
      genotyped 450 chickens with a 600 K SNP array, and sequenced 24 key individuals
      by whole genome re-sequencing. Accuracy of imputation from putative 60 K and 600
      K array data to WGS data was 0.620 and 0.812 for Beagle, and 0.810 and 0.914 for
      FImpute, respectively. By increasing the sequencing cost from 24X to 144X, the
      imputation accuracy increased from 0.525 to 0.698 for Beagle and from 0.654 to
      0.823 for FImpute. With fixed sequence depth (12X), increasing the number of
      sequenced animals from 1 to 24, improved accuracy from 0.421 to 0.897 for FImpute
      and from 0.396 to 0.777 for Beagle. Using optimally selected key individuals
      resulted in a higher imputation accuracy compared with using randomly selected
      individuals as a reference population for re-sequencing. With fixed reference
      population size (24), imputation accuracy increased from 0.654 to 0.875 for
      FImpute and from 0.512 to 0.762 for Beagle as the sequencing depth increased from
      1X to 12X. With a given total cost of genotyping, accuracy increased with the
      size of the reference population for FImpute, but the pattern was not valid for
      Beagle, which showed the highest accuracy at six fold coverage for the scenarios
      used in this study. Conclusions: In conclusion, we comprehensively investigated
      the impacts of several key factors on genotype imputation. Generally, increasing
      sequencing cost gave a higher imputation accuracy. But with a fixed sequencing
      cost, the optimal imputation enhance the performance of WGP and GWAS. An optimal
      imputation strategy should take size of reference population, imputation
      algorithms, marker density, and population structure of the target population and
      methods to select key individuals into consideration comprehensively. This work
      sheds additional light on how to design and execute genotype imputation for
      livestock populations.

PMID- 29581881
TI  - The association between Korean employed workers' on-call work and health
      problems, injuries.
AB  - Background: On-call work is a form of work that requires the person to work at
      any time during the on-call period. Thus, on-call work is often regarded as one
      of the most severe stress factors. This study investigates the associations
      between on-call work and health problems, injuries. Methods: This study was based
      on the 3rd Korean Working Conditions Survey. Total of 29,246 employed workers who
      had been working for at least 1 year were included. Logistic regression analysis
      was performed to investigate the association between on-call work and health
      problems, injuries. Results: The odds ratios for on-call workers in terms of
      physical health problems, psychological health problems, and injuries were 1.33
      (95% confidence interval [CI] 1.22-1.44), 1.31 (95% CI 1.08-1.60), and 2.76 (95%
      CI 2.26-3.37), respectively. Analysis of the detailed symptoms revealed odds
      ratios in on-call workers of 2.06 for hearing problems (95% CI 1.63-2.62); 1.71
      for skin problems (95% CI 1.38-2.12); 1.22 for back pain (95% CI 1.08-1.38); 1.23
      for muscular pains in upper limbs (95% CI 1.12-1.34); 1.27 for muscular pains in
      lower limbs (95% CI 1.15-1.40); 1.46 for headache, eye fatigue (95% CI 1.32
      1.60); 1.37 for abdominal pain (95% CI 1.02-1.85); 1.43 for depression or anxiety
      disorders (95% CI 1.07-1.93); 1.36 for fatigue (95% CI 1.24-1.49); and 1.41 for
      insomnia and general sleep difficulties (95% CI 1.13-1.76). Conclusions: The
      present study found that on-call work results in an increased risk of health
      problems and injuries. This study is the result of analyses of broad range of the
      job spectrum in Korean employed workers; thus, future studies are necessary to
      determine the effects of on-call work in various job groups.

PMID- 29581882
TI  - Developing gene-tagged molecular markers for evaluation of genetic association of
      apple SWEET genes with fruit sugar accumulation.
AB  - Sugar content is an important component of fruit quality. Although sugar
      transporters are known to be crucial for sugar accumulation, the role of genes
      encoding SWEET sugar transporters in fruit sugar accumulation remains elusive.
      Here we report the effect of the SWEET genes on fruit sugar accumulation in
      apple. A total of 25 MdSWEET genes were identified in the apple genome, and 9
      were highly expressed throughout fruit development. Molecular markers of these 9
      MdSWEET genes were developed and used for genotyping of 188 apple cultivars. The
      association of polymorphic MdSWEET genes with soluble sugar content in mature
      fruit was analyzed. Three genes, MdSWEET2e, MdSWEET9b, and MdSWEET15a, were
      significantly associated with fruit sugar content, with MdSWEET15a and MdSWEET9b
      accounting for a relatively large proportion of phenotypic variation in sugar
      content. Moreover, both MdSWEET9b and MdSWEET15a are located on chromosomal
      regions harboring QTLs for sugar content. Hence, MdSWEET9b and MdSWEET15a are
      likely candidates regulating fruit sugar accumulation in apple. Our study not
      only presents an efficient way of implementing gene functional study but also
      provides molecular tools for genetic improvement of fruit quality in apple
      breeding programs.

PMID- 29581883
TI  - NPR1 as a transgenic crop protection strategy in horticultural species.
AB  - The NPR1 (NONEXPRESSOR OF PATHOGENESIS RELATED GENES1) gene has a central role in
      the long-lasting, broad-spectrum defense response known as systemic acquired
      resistance (SAR). When overexpressed in a transgenic context in Arabidopsis
      thaliana, this gene enhances resistance to a number of biotic and abiotic
      stresses. Its position as a key regulator of defense across diverse plant species
      makes NPR1 a strong candidate gene for genetic engineering disease and stress
      tolerance into other crops. High-value horticultural crops face many new
      challenges from pests and pathogens, and their emergence exceeds the pace of
      traditional breeding, making the application of NPR1-based strategies potentially
      useful in fruit and vegetable crops. However, plants overexpressing NPR1
      occasionally present detrimental morphological traits that make its application
      less attractive. The practical utility of NPR-based approaches will be a balance
      of resistance gains versus other losses. In this review, we summarize the
      progress on the understanding of NPR1-centered applications in horticultural and
      other crop plants. We also discuss the effect of the ectopic expression of the A.
      thaliana NPR1 gene and its orthologs in crop plants and outline the future
      challenges of using NPR1 in agricultural applications.

PMID- 29581884
TI  - The BC Glomerulonephritis Network: Improving Access and Reducing the Cost of
      Immunosuppressive Treatments for Glomerular Diseases.
AB  - Glomerulonephritis (GN) is a common cause of end-stage renal disease in Canada
      and worldwide, and results in significant health care resource utilization and
      patient morbidity. However, GN has not been a traditional priority of provincial
      renal health care organizations, despite the known benefits to health services
      delivery and patient outcomes from integrated provincial care in other types of
      chronic kidney disease. To address this deficiency, the British Columbia (BC)
      Provincial Renal Agency created the BC GN Network in 2013 to coordinate
      provincial GN health services delivery informed by robust population-level data
      capture on all GN patients in the province via the BC GN Registry. This report
      describes the use of the BC GN Network infrastructure to systematically develop
      and evaluate a provincial GN drug formulary to improve patient and physician
      access to evidence-based immunosuppressive treatments for GN in a cost-efficient
      manner that successfully halted historical trends of increasing medication costs.
      An example is provided of using the provincial infrastructure to implement and
      subsequently evaluate an evidence-informed health policy of converting brand to
      generic tacrolimus for the treatment of GN. The BC GN Network, including the
      provincial drug formulary and data infrastructure, is an example of the benefits
      of expanding the mandate of provincial renal health administrative organizations
      to include the care of patients with GN, and constitutes a viable health delivery
      model that can be implemented in other Canadian provinces to achieve similar
      goals.

PMID- 29581885
TI  - An Examination of the Application of the Kidney Donor Risk Index in British
      Columbia.
AB  - Background: The Kidney Donor Risk Index (KDRI) is a continuous measure of
      deceased donor kidney transplant failure risk that was derived in US patients
      based on 10 donor characteristics. In the United States, the KDRI is utilized to
      guide organ allocation and to inform clinical decisions regarding organ
      acceptance. Objective: To examine the application of the US-derived KDRI in a
      large Canadian province. Patients: All deceased donor kidney-only transplant
      recipients in British Columbia (BC) between 2005 and 2014. Methods: We examined
      the predictive performance of KDRI in BC transplant recipients and compared the
      overall performance of KDRI with donor age alone in predicting transplant failure
      (from all causes including death). Results: Donors in BC (N = 785) were older but
      included no black donors and few Hepatitis C virus (HCV)-positive donors compared
      with the original derivation cohort of the KDRI in the United States. The KDRI
      was moderately predictive of transplant failure (c statistic, 0.63) and had
      similar predictive performance to donor age alone (c statistic, 0.64).
      Conclusion: Our findings suggest that the US-derived KDRI does not improve the
      prediction of kidney transplant failure compared with donor age alone in a
      Canadian cohort and highlight the need to determine the applicability of KDRI in
      different regions.

PMID- 29581886
TI  - TRIM29 negatively controls antiviral immune response through targeting STING for
      degradation.
AB  - Innate immune system is armed by several lines of pattern recognition receptors
      to sense various viral infection and to initiate antiviral immune response. This
      process is under a tight control and the negative feedback induced by infection
      and/or inflammation is critical to maintain immune homoeostasis and to prevent
      autoimmune disorders, however, the molecular mechanism is not fully understood.
      Here we report TRIM29, a ubiquitin E3 ligase, functions as an inducible negative
      regulator of innate immune response triggered by DNA virus and cytosolic DNA. DNA
      virus and cytosolic DNA stimulation induce TRIM29 expression robustly in
      macrophages and dendritic cells, although the basal level of TRIM29 is
      undetectable in those cells. TRIM29 deficiency elevates IFN-I and proinflammatory
      cytokine production upon viral DNA and cytosolic dsDNA stimulation. Consistently,
      in vivo experiments show that TRIM29-deficient mice are more resistant to HSV-1
      infection than WT controls, indicated by better survival rate and reduced viral
      load in organs. Mechanism studies suggest that STING-TBK1-IRF3 signaling pathway
      in TRIM29 KO cells is significantly enhanced and the degradation of STING is
      impaired. Furthermore, we identify that TRIM29 targets STING for K48
      ubiquitination and degradation. This study reveals TRIM29 as a crucial negative
      regulator in immune response to DNA virus and cytosolic DNA, preventing potential
      damage caused by overcommitted immune responses.

PMID- 29581888
TI  - Concerns on a new therapy for severe heart failure using cell sheets with
      skeletal muscle or myocardial cells from iPS cells in Japan.
AB  - In Japan, a new therapy for severe heart failure using skeletal myocardial sheet
      is ongoing and a treatment using iPS cells is just about to start. However, I
      think there are problems and concerns. In this comment, I will express concerns
      on these treatments. This will be useful and interesting to stem cell researchers
      and clinical cardiologists.

PMID- 29581887
TI  - Improving imputation in disease-relevant regions: lessons from cystic fibrosis.
AB  - Does genotype imputation with public reference panels identify variants
      contributing to disease? Genotype imputation using the 1000 Genomes Project (1KG;
      2504 individuals) displayed poor coverage at the causal cystic fibrosis (CF)
      transmembrane conductance regulator (CFTR) locus for the International CF Gene
      Modifier Consortium. Imputation with the larger Haplotype Reference Consortium
      (HRC; 32,470 individuals) displayed improved coverage but low sensitivity of
      variants clinically relevant for CF. A hybrid reference that combined whole
      genome sequencing (WGS) from 101 CF individuals with the 1KG imputed a greater
      number of single-nucleotide variants (SNVs) that would be analyzed in a genetic
      association study (r2 >= 0.3 and MAF >= 0.5%) than imputation with the HRC, while
      the HRC excelled in the lower frequency spectrum. Using the 1KG or HRC as
      reference panels missed the most common CF-causing variants or displayed low
      imputation accuracy. Designs that incorporate population-specific WGS can improve
      imputation accuracy at disease-specific loci, while imputation using public data
      sets can omit disease-relevant genotypes.

PMID- 29581889
TI  - Non-traumatic myelopathy associated with prolonged hyperextension during
      swimming: an unusual variation of Surfer's Myelopathy.
AB  - Introduction: Surfer's myelopathy (SM) is a rare cause on non-traumatic acute
      myelopathy. This has classically been described in novice surfers however has
      been reported in other scenarios. Case presentation: We present a case of non
      traumatic paraparesis associated with prolonged cervical hyperextension during
      swimming with imaging characteristics consistent with an unusual variation of SM
      in a swimmer. Discussion: SM and its variants should be considered in the
      differential diagnosis of any patient presenting with an anterior spinal cord
      syndrome with a history of either sustained or repeated spinal hyperextension.

PMID- 29581890
TI  - Recurrent discitis in the acute rehab setting: a case report.
AB  - Introduction: Discitis is an infection of the intervertebral disc space that can
      lead to paralysis, sepsis, epidural abscess, or other life-threatening
      complications if left untreated and may sometimes present with limited laboratory
      abnormalities to clue a diagnosis. Case presentation: We present a case of a 67
      year-old female in an acute rehabilitation setting who had presenting symptoms of
      sudden unexplained back pain refractory to pain control. She had a previous
      history of discitis and multiple failed knee replacement surgeries secondary to
      MSSA infections. Although vitals and basic labs were within normal limits, we
      recognized the clinical presentation as an indicator to order inflammatory
      markers (CPR and ESR), which were elevated compared to levels on admission, and
      subsequently ordered imaging and blood cultures to detect a case of recurrent
      worsening discitis. Discussion: We highlight the presentation of recurrent
      discitis and necessary low threshold needed to detect such recurrence in patients
      with a previous history of discitis that have sudden unexplained back pain with
      no other usual physical or laboratory indicators of infection.

PMID- 29581891
TI  - Multifocal primary melanoma of the cervical spinal cord successfully treated by
      tumorectomy: a case report.
AB  - Introduction: Multifocal primary melanoma of the spine is extremely rare. Here,
      we report a case of multifocal primary melanoma of the cervical spinal cord. Case
      presentation: A 39-year-old man presented with a 1-year history of numbness of
      the upper extremities and back. Magnetic resonance imaging of the cervical spine
      suggested multifocal intradural extramedullary tumors at levels C2 and C4-C5. A
      diagnostic biopsy revealed a pathological diagnosis of malignant melanoma.
      Tumorectomy was then performed. The numbness in the patient's upper extremities
      improved, and he was discharged. As of 2 years after surgery, no signs of local
      or systemic recurrence have been noted. Discussion: Primary melanoma of the
      spinal cord usually carries a poor prognosis. However, in this case, the outcome
      following tumorectomy has been highly favorable. We speculate that this is
      because the MIB-1 labeling index of the tumors was less than 1%.

PMID- 29581892
TI  - Primary intramedullary spinal cord tumour in pregnancy: a case report.
AB  - Introduction: Primary spinal cord tumours can lead to severe neurological
      complications and even death. Pregnant women often complain of discomfort of the
      lower limbs, which is usually caused by sciatica. Here we present the case of a
      pregnant woman, who was initially considered to have sciatica, but was finally
      diagnosed with a primary intramedullary spinal cord tumour. Case presentation: A
      28-year-old pregnant woman presented to our hospital with inexplicable numbness
      in her lower limbs. She was initially considered to have sciatica, but acute
      deterioration of neurological symptoms and plain magnetic resonance imaging (MRI)
      findings suggested malignancy. The patient was finally diagnosed with a primary
      intramedullary spinal cord tumour at the C3-Th5 region. An emergency caesarean
      section was performed, after which the spinal cord lesion was evaluated using
      contrast-enhanced MRI, positron emission tomography with 2-deoxy-2-[fluorine-18]
      fluoro-d-glucose integrated with computed tomography, and spinal angiography, and
      further treatment was initiated. However, while the patient's spinal cord tumour
      surgery was performed in early postpartum, her paraplegia and bladder and rectal
      disturbances remained unchanged even 1 year after surgery. Discussion: Because of
      the low incidence of spinal cord tumours during pregnancy, no definite reports
      have been published on the treatment of pregnant patients with spinal cord
      tumours. Although safe imaging tests during pregnancy are limited, intervention
      in such patients should be performed as early as possible to avoid irreversible
      neurological deterioration.

PMID- 29581893
TI  - Effect of indoor wheelchair curling training on trunk control of person with
      chronic spinal cord injury: a randomised controlled trial.
AB  - Study design: Randomised, controlled, single-blind crossover design study.
      Objective: Effect of indoor wheelchair curling training on trunk control of a
      person with chronic spinal cord injury (SCI). Setting: SCI Centre of Balgrist
      University Hospital in Zurich, Switzerland. Methods: The trunk control of 13
      subjects was assessed by the modified functional reach test (MFRT) and nonlinear
      dynamic systems analysis (NDSA) before and after eight indoor curling training
      sessions and compared to everyday life over 4 weeks. Results: The attendance rate
      was 95% during the training sessions. There were no adverse events. Neither the
      MRFT nor the NDSA showed any significant differences in the sitting stability.
      The subjects subjectively reported improved physical feeling, an increase in
      their trunk control and strength; 39% of the participants wanted to continue the
      training. Conclusions: With subjective improvements and no adverse events, indoor
      wheelchair curling training is a safe physical activity for people with SCI.
      Wheelchair curling offers a suitable alternative to sports already used in
      rehabilitation and in recreational activities of a person with SCI. In order to
      be able to draw more unambiguous conclusions from the training method for trunk
      control and to answer the question of the study unambiguously, the number of
      subjects would have to be greater and the test methods should provide more exact
      and specific measurements.

PMID- 29581895
TI  - Methamphetamine alters T cell cycle entry and progression: role in immune
      dysfunction.
AB  - We and others have demonstrated that stimulants such as methamphetamine (METH)
      exerts immunosuppressive effects on the host's innate and adaptive immune systems
      and has profound immunological implications. Evaluation of the mechanisms
      responsible for T-cell immune dysregulation may lead to ways of regulating immune
      homeostasis during stimulant use. Here we evaluated the effects of METH on T cell
      cycle entry and progression following activation. Kinetic analyses of cell cycle
      progression of T-cell subsets exposed to METH demonstrated protracted G1/S phase
      transition and differentially regulated genes responsible for cell cycle
      regulation. This result was supported by in vivo studies where mice exposed to
      METH had altered G1 cell cycle phase and impaired T-cell proliferation. In
      addition, T cells subsets exposed to METH had significant decreased expression of
      cyclin E, CDK2 and transcription factor E2F1 expression. Overall, our results
      indicate that METH exposure results in altered T cell cycle entry and
      progression. Our findings suggest that disruption of cell cycle machinery due to
      METH may limit T-cell proliferation essential for mounting an effective adaptive
      immune response and thus may strongly contribute to deleterious effect on immune
      system.

PMID- 29581894
TI  - Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards
      ischemic neuronal death.
AB  - Cell cycle proteins are mainly expressed by dividing cells. However, it is well
      established that these molecules play additional non-canonical activities in
      several cell death contexts. Increasing evidence shows expression of cell cycle
      regulating proteins in post-mitotic cells, including mature neurons, following
      neuronal insult. Several cyclin-dependent kinases (Cdks) have already been shown
      to mediate ischemic neuronal death but Cdk1, a major cell cycle G2/M regulator,
      has not been investigated in this context. We therefore examined the role of Cdk1
      in neuronal cell death following cerebral ischemia, using both in vitro and in
      vivo genetic and pharmacological approaches. Exposure of primary cortical neurons
      cultures to 4 h of oxygen-glucose deprivation (OGD) resulted in neuronal cell
      death and induced Cdk1 expression. Neurons from Cdk1-cKO mice showed partial
      resistance to OGD-induced neuronal cell death. Addition of R-roscovitine to the
      culture medium conferred neuroprotection against OGD-induced neuronal death.
      Transient 1-h occlusion of the cerebral artery (MCAO) also leads to Cdk1
      expression and activation. Cdk1-cKO mice displayed partial resistance to
      transient 1-h MCAO. Moreover, systemic delivery of R-roscovitine was
      neuroprotective following transient 1-h MCAO. This study demonstrates that
      promising neuroprotective therapies can be considered through inhibition of the
      cell cycle machinery and particularly through pharmacological inhibition of Cdk1.

PMID- 29581896
TI  - Chasing the signaling run by tri-molecular time-lapse FRET microscopy.
AB  - A feasible design is made to measure three protein/protein interactions to
      visualize signal pathways by time-lapse Forster resonance energy transfer (FRET)
      microscopy. When interacting proteins are in close proximity, excitation energy
      is provided to allow the energy flow from the first molecule to excite the
      second, followed by energy transfer to the third. By phorbol ester/calcium
      ionophore stimulation, for example, a real-time complex formation of ectopic
      IkappaBalpha/ERK/WWOX occurs as measured by FRET microscopy, indicative of an
      ongoing functional signaling. Hyaluronan induces membrane Hyal-2 signaling, which
      allows FRET measurement of the complex formation of ectopic Smad4/WWOX/Hyal-2 for
      causing bubbling cell death. If ectopic p53 is recruited to replace Hyal-2, the
      resulting ectopic Smad4/WWOX/p53 complex induces membrane blebbing without cell
      death. Together, in this perspective review article, we demonstrate the
      utilization of time-lapse FRET microscopy to visualize the signaling event via
      the tri-molecular protein complex formation and their biological outcomes. We
      show an initial two-protein binding to form the driving force to jumpstart the
      tri-molecular execution for the signal pathway.

PMID- 29581898
TI  - Giant Left Ventricular Thrombus in a Patient with Acute Ischemic Stroke: A Case
      Report and Minireview.
AB  - A 56-year-old healthy male with no obvious risk factors or significant past
      medical history was admitted to the emergency room with acute ischemic stroke. On
      his transthoracic echocardiography (TTE), an extremely large thrombus was
      detected at the apex involving the distal anterior wall. The thrombus was
      predominantly adherent but with a mobile tip. The patient was subsequently
      managed with dual antiplatelet therapy. In this report, we present an interesting
      case of an acute ischemic stroke secondary to a giant left ventricular thrombus
      in a patient with no past significant cardiac or neurologic medical history.

PMID- 29581899
TI  - Successful Rotational Atherectomy for an Angulated Calcified Lesion in an
      Anomalous Right Coronary Artery Using the "Mother-and-Child" Technique.
AB  - Percutaneous coronary intervention (PCI) involving the anomalous coronary artery
      is challenging with respect to difficulty in achieving stable catheterization.
      Rotational atherectomy (RA) can facilitate severely calcified lesions to improve
      stent delivery and stent expansion; however, its utility in tortuous and
      angulated coronary arteries is limited with difficulty in delivery of the RA
      burr. The mother-and-child technique is effective for complex PCIs with increased
      backup force for device delivery in such complicated cases. We report a case of
      successful rotational atherectomy using the "mother-and-child" technique with a
      Dio thrombus aspiration catheter for an angulated calcified lesion in an
      anomalous origin of the right coronary artery.

PMID- 29581897
TI  - Baseline mapping of Lassa fever virology, epidemiology and vaccine research and
      development.
AB  - Lassa fever (LF) is a zoonotic disease associated with acute and potentially
      fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the
      family Arenaviridae. It is generally assumed that a single infection with LASV
      will produce life-long protective immunity. This suggests that protective
      immunity induced by vaccination is an achievable goal and that cell-mediated
      immunity may play a more important role in protection, at least following natural
      infection. Seropositive individuals in endemic regions have been shown to have
      LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and
      glycoprotein precursor (GPC), suggesting that these will be important vaccine
      immunogens. The role of neutralizing antibodies in protective immunity is still
      equivocal as recent studies suggest a role for neutralizing antibodies. There is
      extensive genetic heterogeneity among LASV strains that is of concern in the
      development of assays to detect and identify all four LASV lineages. Furthermore,
      the gene disparity may complicate the synthesis of effective vaccines that will
      provide protection across multiple lineages. Non-human primate models of LASV
      infection are considered the gold standard for recapitulation of human LF. The
      most promising vaccine candidates to date are the ML29 (a live attenuated
      reassortant of Mopeia and LASV), vesicular stomatitis virus (VSV) and vaccinia
      vectored platforms based on their ability to induce protection following single
      doses, high rates of survival following challenge, and the use of live virus
      platforms. To date no LASV vaccine candidates have undergone clinical evaluation.

PMID- 29581900
TI  - Autotransplantation and Orthodontic Treatment after Maxillary Central Incisor
      Region Trauma: A 13-Year Follow-Up Case Report Study.
AB  - The anterior maxilla is the most prone region to the trauma during childhood, and
      tooth loss sometimes happens due to trauma. Replacing the missing teeth has
      always been one of the dentists' challenges in children and adolescents, since
      their dentofacial growth is not complete. Autotransplantation of mandibular
      premolars with two-thirds or three-quarters of root formation provides the best
      prognosis for the tooth survival. This case report describes the management of a
      10-year-old boy suffering a severe dental injury who received the
      autotransplantation of the premolars from mandible to restore the space caused by
      trauma in maxillary central incisor region and a 13-year follow-up of the
      autotransplantation.

PMID- 29581901
TI  - Regenerative Endodontic Treatment of a Maxillary Mature Premolar.
AB  - Regenerative endodontic treatment was performed on a mature maxillary premolar
      diagnosed as chronic pulpitis. The root canals were chemomechanically prepared
      and placed intracanal medicaments at the first appointment. Then 2 weeks later, a
      blood clot was created in the canals, over which mineral trioxide aggregate was
      placed. At 6-month follow-up, cementum-like tissue seemed to be formed in the
      root canal along with nearly recovered pulp vitality. At 12-month recall, the
      radiographic results revealed evidence of root wall thickening. At 30-month
      recall, no periapical lesion was found. This case report indicates that
      regenerative endodontic treatment for the mature premolar is feasible. More cases
      are needed for further validation.

PMID- 29581902
TI  - Sectional Fixed Orthodontic Extrusion Technique in Management of Teeth with
      Complicated Crown-Root Fractures: Report of Two Cases.
AB  - Complicated crown-root fractures account for a small percentage of traumatic
      dental injuries seen in children; however, management of these injuries can be
      very challenging to clinicians. Factors such as complexity of the injury,
      patient's age and dentition stage, patient's cooperation, and parental demands
      may have some bearing on the type of treatment undertaken and its outcomes. In
      some children, these injuries may have significant impact on their quality of
      life. The purpose of this article is to describe two cases of complicated crown
      root fracture which were successfully managed through orthodontic extrusion using
      a sectional fixed orthodontic technique. The basis for the treatment technique
      and its favourable outcomes were highlighted with its advantages and drawbacks.

PMID- 29581903
TI  - Ingested Foreign Body Migration to the Liver: An Unusual Cause of Persistent
      Abdominal Pain in a 54-Year-Old Female.
AB  - Abdominal pain is a common presentation in emergency medicine. We describe the
      case of a 54-year-old female who presented to the emergency department due to
      worsening abdominal pain. She had a history of right upper quadrant (RUQ)
      abdominal pain that had been ongoing for several months. The pain had been
      thought by the primary care team to be related to gastritis and she had been
      prescribed a proton pump inhibitor (PPI). Her abdominal pain increased in the
      three days prior to her presentation to the emergency department (ED). The
      computed tomography (CT) scan of the abdomen showed a foreign body (FB) in the
      liver which was successfully removed surgically. Pathology results showed that
      the FB was consistent with a small bone fragment. Ingestions of FB are common but
      seldom result in complications. When complications do arise, perforation of a
      hollow viscous is typically seen. Rarely, transmigration of the FB can occur.

PMID- 29581904
TI  - Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?
AB  - Background: Metformin is widely known as an antidiabetic agent which has
      significant gastrointestinal side effects, but nightmares and abnormal dreams as
      its adverse reactions are not well reported. Case Presentation: Herein we present
      a case of 56-year-old male patient with no known history of recurrent nightmares
      and sleep disorder, experiencing nightmare and abnormal dreams directly after
      consumption of 750 mg extended release metformin. He reported his dream as an
      unpleasant experience which awakened him at night with negative feelings. The
      nightmare only lasted for a night, but his dreams every night thereafter seemed
      abnormal. The dreams were vivid and indescribable. The disappearance and
      occurrence of abnormal dreams ensued soon after the drug was discontinued and
      rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR)
      probability scale and resulted as probable causality. Conclusion: Metformin might
      be the underlying cause of nightmare and abnormal dreams in this patient. More
      studies are needed to confirm the association and causality of this findings.

PMID- 29581905
TI  - Antiphospholipid Antibody Induced by Nivolumab.
AB  - Nivolumab is a monoclonal antibody against the programmed death protein 1 and is
      used for patients with advanced melanoma. It is associated with potentially
      immune-related adverse events, including disorders of the skin, GI tract, and the
      thyroid; these disorders were successfully treated with prednisone and
      infliximab. Other immunotherapeutic agents were observed to induce the formation
      of antiphospholipid antibody (APA) including alpha-interferon and interleukin-2.
      We present a case of APA development after the third dose of nivolumab in a 71
      year-old male with advanced melanoma. The APA was detected after finding a
      prolonged aPTT; the lupus anticoagulant assay tested positive. The patient was
      treated with prednisone but, unfortunately, he expired a few days later.

PMID- 29581907
TI  - Pregnancy after Prosthetic Aortic Valve Replacement: How Do We Monitor Prosthetic
      Valvular Function during Pregnancy?
AB  - Background: With modern medicine, many women after structural heart repair are
      deciding to experience pregnancy. There is a need for further study to identify
      normal echocardiographic parameters to better assess prosthetic valvular function
      in pregnancy. In addition, a multidisciplinary approach is essential in managing
      pregnant patients with complex cardiac conditions. Case: A 22-year-old
      nulliparous woman with an aortic valve replacement 18 months prior to her
      pregnancy presented to prenatal care at 20-week gestation. During her prenatal
      care, serial echocardiography showed a significant increase in the mean gradient
      across the prosthetic aortic valve. Multidisciplinary management and a serial
      echocardiography played an integral role in her care that resulted in a
      successful spontaneous vaginal delivery without complications. Conclusion:
      Further characterization of the normal echocardiographic parameters in pregnant
      patients with prosthetic valves is critical to optimize prenatal care for this
      patient population. This case report is novel in that serial echocardiograms were
      obtained throughout prenatal care, which showed significant changes across the
      prosthetic aortic valve. Teaching Points: (1) Further study is needed to identify
      normal echocardiographic parameters to best assess prosthetic valvular function
      in pregnancy. (2) Multidisciplinary management is encouraged to optimize prenatal
      care for women with prosthetic aortic valve replacements.

PMID- 29581906
TI  - The Cytoreductive Effect of Radiotherapy for Small Cell Ovarian Carcinoma of the
      Pulmonary Type: A Case Report and Review of the Literature.
AB  - Small cell ovarian carcinoma of the pulmonary type is a rare and highly
      aggressive tumor for which a suitable treatment strategy has not been
      established. A 45-year-old woman presented with abdominal swelling, and primary
      ovarian carcinoma was suspected. The postoperative pathological diagnosis was
      small cell ovarian carcinoma of the pulmonary type. She also had complicated
      grade 1 endometrioid carcinoma of the uterine corpus. Three courses of cisplatin
      and etoposide therapy were administered as adjuvant chemotherapy. Because the
      tumor was chemotherapy resistant, she underwent palliative abdominal irradiation
      at a dose of 26 Gy in 13 fractions, which induced cytoreduction and provided
      symptomatic relief. She died 4 months after surgery. Lactate dehydrogenase was a
      useful tumor marker during treatment. Here, we present an extremely rare case of
      a patient with small cell ovarian carcinoma of the pulmonary type treated with
      radiotherapy after surgery and chemotherapy.

PMID- 29581908
TI  - Sarcomatoid Variant of Urothelial Carcinoma of the Renal Pelvis with Inferior
      Vena Cava Tumour Thrombus: A Case Report and Literature Review.
AB  - Sarcomatoid variant of urothelial carcinoma (SVUC) of the renal pelvis is a rare
      entity. To the best of our knowledge, around 25 cases of this neoplasm have been
      reported in the literature to date, most of which were of high stage. The
      inferior vena cava tumour thrombus, which is a hallmark of renal cell carcinoma
      (RCC), may rarely be found in urothelial carcinoma of renal pelvis. In this
      report, a case of SVUC associated with tumour extension to inferior vena cava is
      documented. This association has been encountered in only one previously reported
      case. The possibility of urothelial carcinoma of the renal pelvis should
      therefore be included in the differential diagnosis of tumour thrombus of the
      inferior vena cava.

PMID- 29581909
TI  - Mechanically induced Ca2+ oscillations in osteocytes release extracellular
      vesicles and enhance bone formation.
AB  - The vast osteocytic network is believed to orchestrate bone metabolic activity in
      response to mechanical stimuli through production of sclerostin, RANKL, and
      osteoprotegerin (OPG). However, the mechanisms of osteocyte mechanotransduction
      remain poorly understood. We've previously shown that osteocyte
      mechanosensitivity is encoded through unique intracellular calcium (Ca2+)
      dynamics. Here, by simultaneously monitoring Ca2+ and actin dynamics in single
      cells exposed to fluid shear flow, we detected actin network contractions
      immediately upon onset of flow-induced Ca2+ transients, which were facilitated by
      smooth muscle myosin and further confirmed in native osteocytes ex vivo.
      Actomyosin contractions have been linked to the secretion of extracellular
      vesicles (EVs), and our studies demonstrate that mechanical stimulation
      upregulates EV production in osteocytes through immunostaining for the secretory
      vesicle marker Lysosomal-associated membrane protein 1 (LAMP1) and quantifying EV
      release in conditioned medium, both of which are blunted when Ca2+ signaling was
      inhibited by neomycin. Axial tibia compression was used to induce anabolic bone
      formation responses in mice, revealing upregulated LAMP1 and expected
      downregulation of sclerostin in vivo. This load-related increase in LAMP1
      expression was inhibited in neomycin-injected mice compared to vehicle. Micro
      computed tomography revealed significant load-related increases in both
      trabecular bone volume fraction and cortical thickness after two weeks of
      loading, which were blunted by neomycin treatment. In summary, we found
      mechanical stimulation of osteocytes activates Ca2+-dependent contractions and
      enhances the production and release of EVs containing bone regulatory proteins.
      Further, blocking Ca2+ signaling significantly attenuates adaptation to
      mechanical loading in vivo, suggesting a critical role for Ca2+-mediated
      signaling in bone adaptation.

PMID- 29581910
TI  - Rehabilitation Outcomes for Total Knee Arthroplasties: Continuous Adductor Canal
      Block Versus Continuous Femoral Nerve Block.
AB  - Objective: To determine whether any strength, range of motion (ROM), or
      functional improvement exists in the adductor canal block (ACB) group after
      completion of inpatient rehabilitation and following the removal of the
      continuous block. Design: Retrospective cohort. Setting: Inpatient rehabilitation
      at discharge and outpatient orthopedic clinic for follow-up. Participants: Two
      hundred forty-six consecutive primary total knee arthroplasties (TKAs; N = 221
      patients) performed by a single surgeon in a single institution between July 2013
      and August 2015 for a diagnosis of osteoarthritis. Interventions: All TKA cases
      received a continuous femoral nerve block (FNB) from July 2013 to August 2014 for
      postoperative pain control. From August 2014 through August 2015, all TKAs
      received a continuous ACB. Main Outcome Measures: Manual muscle tests (MMTs; 0-5
      scale) of the quadriceps and passive ROM of the knee were assessed at 3 time
      periods (hospital discharge [HD], 1-2 weeks, and 1 month). Patient-oriented
      outcomes and clinical knee scores were examined preoperatively and
      postoperatively at 3 and 6 months. Results: 63.6% of FNB cases had an MMT less
      than 3 at HD and 36.4% of FNB cases had an MMT of 3 or greater at HD. Conversely,
      46% of ACB cases had an MMT less than 3 at HD and 54% had an MMT of 3 or greater
      at HD. There were no statistically significant differences in all postoperative
      variables at all tested time periods. Conclusions: This study showed no short
      term postoperative advantages in the ACB group after catheter removal. The
      superior inpatient rehabilitation course in the continuous ACB group is likely
      not long enough to translate into any maintained benefit following catheter
      removal. Nevertheless, the trend toward greater strength in the ACB group in the
      immediate short term at HD warrants further investigation.

PMID- 29581911
TI  - Fevers in Adult Lupus Patients.
AB  - Variability in systemic lupus erythematosus (SLE) disease manifestations is well
      recognized. Lupus disease activity can range from mild to severe. Fever is a
      common manifestation of SLE and occurs in 36%-86% of patients. In the Modified
      Systemic Lupus Erythematosus Disease Activity Index (M-SLEDAI), fever is taken
      into account as disease activity scoring. Assessment of lupus patients with fever
      is an important diagnostic challenge, since the initial clinical presentation of
      a patient with lupus is very similar to the acute febrile phase of an infection.
      The attribution of fever to SLE holds only after other causes are excluded.

PMID- 29581912
TI  - Massive Intradural Chondroma Masquerading as Lower Body Parkinsonism.
AB  - Intracranial chondromas of the dural convexity are exceedingly rare with less
      than 30 reported in the literature to date. We report a massive intradural
      convexity chondroma in a patient initially thought to have a frontal gait
      neurodegenerative disorder. This large tumor required a complex, piecemeal
      surgical resection due to the dense, fibrous nature of the tumor and the
      proximity of crucial structures. The patient had complete resolution of her
      preoperative symptoms after surgical excision.

PMID- 29581913
TI  - Respiratory Rate Variability as a Prognostic Factor in Hospitalized Patients
      Transferred to the Intensive Care Unit.
AB  - Introduction Increasing mortality rates within the intensive care unit (ICU) is
      an ever growing problem, ultimately leading to increases in the cost of
      healthcare expenditures. Currently, there are attempts to use guidelines in the
      hospital setting to predict overall mortality in critically ill patients.
      However, a predictor of subsequent ICU admissions remains to be explored. Recent
      data has shown the importance of monitoring respiratory rate variability (RRV) as
      a useful predictor of the deterioration of patients. Respiratory rate, in
      comparison to blood pressure or pulse rate, is deemed as the better determinant
      in identifying high-risk patients. Aim Our study aims to assess the role of RRV
      monitoring as a potential prognostic marker predictive of ICU admission. Results
      There was a significant (p = 0.009) increase in RRV between the third and fourth
      set of respiratory rates prior to ICU admission, such that coefficient of
      variation percentage (CV%) increased from 0.3% (95% confidence interval (CI):
      0.09 - 0.42) to 0.7% (95% CI: 0.04 - 0.9) about 12 hours before admission to the
      ICU independent from diagnosis. Conclusion Using elevated RRV as a signal may be
      a useful prognostic tool in providing early intervention, thus reducing the
      incidence of subsequent morbidity and mortality in patients that might
      necessitate an ICU admission.

PMID- 29581914
TI  - Pepto-Bismol Tablets Resembling Foreign Bodies on Abdominal Imaging.
AB  - A 28-year-old female presented to the emergency department (ED) with a one-day
      history of severe, diffuse abdominal pain of sudden onset. In the ED, an
      abdominal x-ray was done, which showed two hyperdense disc-shaped structures.
      When her abdominal pain did not subside, the ED performed a computerized
      tomography (CT) scan of the abdomen and pelvis with contrast, which showed the
      two previously noted 16 mm disc-shaped objects to actually be located within the
      cecum. Based on the history and imaging, it was deduced that the two discs were
      likely to be Pepto-Bismol tablets (Proctor & Gamble Co., Cincinnati, OH). Most
      medications are radiolucent, but there are some that are radiopaque, including
      Pepto-Bismol (also known as bismuth subsalicylate). While quite a rare
      occurrence, it is important to know about since it can lead to unnecessary
      endoscopy and patient anxiety.

PMID- 29581915
TI  - Four-year Survival (and Counting) after Stereotactic Radiosurgery to Nearly 100
      Brain Metastases: A Case Report.
AB  - Brain metastases are a relatively common consequence of Stage IV melanoma.
      Historically, patients with brain metastases fare poorly, with median survival of
      only weeks to months. Patients with multiple metastases in the brain have often
      been overlooked in the literature, with the focus being placed more on patients
      with only a small number of metastases. The authors present a case of a 42-year
      old man with a total of 98 brain metastases treated over several Gamma Knife
      sessions. He is nearly five years out from his initial treatment. This case
      highlights the fact that there is a large amount of variability in survival after
      diagnosis with brain metastases. Selection for treatment should be based on the
      clinical picture and clinicians should take care to avoid selection bias in this
      population.

PMID- 29581916
TI  - Hip Fracture in a Patient with Primary Hyperparathyroidism: Medical and Surgical
      Lessons.
AB  - Hyperparathyroidism is a condition which can be primary, secondary or tertiary
      and is characterized by increased calcium levels, low phosphate levels, and
      elevated parathyroid hormone (PTH) levels. Primary hyperthyroidism can cause
      severe bone resorption leading to bone pains and pathological fracture. We
      present the case of a patient with severe primary hyperparathyroidism with an
      atraumatic fracture at the neck of the femur and multiple medical comorbidities
      presenting a surgical challenge. While primary hyperparathyroidism is rare, it
      should be considered during differential diagnoses.

PMID- 29581917
TI  - Idiopathic Cutis Verticis Gyrata in a Female.
AB  - Cutis verticis gyrata (CVG) is a benign proliferation and hypertrophy involving
      the scalp which exhibits furrows resembling the cerebral cortex convolutions. The
      diagnosis of CVG is based on clinical findings. Complementary investigations are
      recommended to rule out local or systemic underlying disorders. Idiopathic or
      essential primary CVG refers to cases without obvious origin and with no other
      associated abnormalities. These forms affect mainly men. Herein, the authors
      present a new observation of an idiopathic CVG in a female, which seems to be
      extremely rare.

PMID- 29581918
TI  - Steroids and Thyrotoxicosis Precipitate Periodic Paralysis.
AB  - Thyrotoxic Periodic Paralysis (TPP) belongs to a group of muscle diseases called
      channelopathies, which present with painless generalized muscle weakness without
      exertion. TPP can be precipitated by a large carbohydrate meal, stress, strenuous
      exercise, alcohol, a high-salt diet, menstruation, and cold temperatures. Rarely,
      steroids such as dexamethasone can also precipitate a TPP attack. A 29-year-old
      Hispanic male, with a history of hyperthyroidism, presented to the emergency
      department with progressive weakness, predominantly in the lower extremities
      since morning. Earlier that day, the patient was seen in the same emergency
      department for difficulty in swallowing. He was diagnosed with uvulitis and
      received intramuscular dexamethasone and was discharged with amoxicillin for ten
      days. At home, he started to develop cramps in his lower extremities associated
      with paresthesias, which progressed to severe weakness to the point where he
      could not get out of bed. He returned to the hospital and revealed that he had
      suffered a similar episode following a steroid injection five years ago. He had
      not sought medical attention as it resolved spontaneously. He denied strenuous
      exercise, carbohydrate-rich meal, or alcohol ingestion. The patient had been
      noncompliant with atenolol and methimazole for the past month after losing his
      medical insurance. On examination, the patient appeared alert and calm. His
      vitals were significant for tachycardia of 123 beats per minute. Thyromegaly and
      tenderness were absent on examination of the neck. Muscle strength was 5/5 in the
      ankle dorsiflexors and ankle plantar flexors bilaterally, but the strength of the
      iliopsoas, quadriceps, and hamstrings was only 2/5 bilaterally. Deep tendon
      reflexes were diminished throughout to 1+. Laboratory findings were significant
      for profound hypokalemia, hypophosphatemia, low thyroid stimulating hormone, and
      elevated free T3 and T4 levels suggestive of hyperthyroidism. His electrolytes
      were replaced aggressively and his home medications were restarted. His
      electrolyte imbalance corrected and his symptoms resolved within a day and he was
      discharged home. The overwhelming majority of TPP cases reported are male
      patients, hence this case demonstrates the need to be aware of this complication
      while treating hyperthyroid male patients with steroids. Hyperthyroidism
      potentiates catecholamine-mediated Na/K ATPase transport of potassium into the
      cells. Glucocorticoids are used in the treatment of thyroid storm as it prevents
      the peripheral conversion of T4 to T3. Moreover, glucocorticoids increase glucose
      levels stimulating insulin release, which shifts potassium intracellularly
      accentuating muscle weakness. Although the incidence of glucocorticoids causing
      TPP is low and not many cases are documented, it is still an important condition
      to be aware of and can have major clinical implications. Clinicians should be
      aware of this small subset of hyperthyroidism patients where the use of
      glucocorticoids can precipitate paralysis.

PMID- 29581919
TI  - Liver Abscesses Caused by Streptococcus intermedius in an Immunocompromised
      Patient.
AB  - Streptococcus intermedius is a Gram-positive bacterium that is part of the normal
      flora in the oral cavity, as well as in the upper respiratory, female urogenital,
      and gastrointestinal tracts. It may also be found in human feces and is the
      dominant species found in subgingival plaque. We present a case of a 50-year-old
      man who came to the emergency room with abdominal pain for weeks associated with
      nausea and vomiting, diarrhea, and fever. A computed tomography (CT) scan of the
      abdomen showed numerous cysts throughout the liver. The patient was started on
      intravenous (IV) antibiotics and fluid from two of the liver abscesses was
      obtained for culture.

PMID- 29581920
TI  - First Clinical Applications of a High-Definition Three-Dimensional Exoscope in
      Pediatric Neurosurgery.
AB  - The ideal visualization tools in microneurosurgery should provide magnification,
      illumination, wide fields of view, ergonomics, and unobstructed access to the
      surgical field. The operative microscope was the predominant innovation in modern
      neurosurgery. Recently, a high-definition three-dimensional (3D) exoscope was
      developed. We describe the first applications in pediatric neurosurgery. The
      VITOM 3D exoscope (Karl Storz GmbH, Tuttlingen, Germany) was used in pediatric
      microneurosurgical operations, along with an OPMI PENTERO operative microscope
      (Carl Zeiss AG, Jena, Germany). Experiences were retrospectively evaluated with
      five-level Likert items regarding ease of preparation, image definition,
      magnification, illumination, field of view, ergonomics, accessibility of the
      surgical field, and general user-friendliness. Three operations were performed:
      supratentorial open biopsy in the supine position, infratentorial brain tumor
      resection in the park bench position, and myelomeningocele closure in the prone
      position. While preparation and image definition were rated equal for microscope
      and exoscope, the microscope's field of view, illumination, and user-friendliness
      were considered superior, while the advantages of the exoscope were seen in
      ergonomics and the accessibility of the surgical field. No complications
      attributed to visualization mode occurred. In our experience, the VITOM 3D
      exoscope is an innovative visualization tool with advantages over the microscope
      in ergonomics and the accessibility of the surgical field. However, improvements
      were deemed necessary with regard to field of view, illumination, and user
      friendliness. While the debate of a "perfect" visualization modality is
      influenced by personal preference, this novel visualization device has the
      potential to become a valuable tool in the neurosurgeon's armamentarium.

PMID- 29581921
TI  - Posterior Vitreous Detachment Precipitated by Yoga.
AB  - Yoga has recently been touted as a means to improve physical and mental well
      being. However, no form of exercise is without its risks. A 32-year-old Chinese
      female with moderate myopia complained of right eye sudden onset of floaters and
      mild blurring of vision after the head-down posture. The visual acuity was 6/12
      in the right eye and 6/9 in the left eye. A right eye fundus examination showed
      posterior vitreous detachment, with a small blood clot located at the inferior
      margin of the optic disc. The patient was diagnosed with right eye vitreous
      hemorrhage secondary to acute posterior vitreous detachment and was managed
      conservatively. Acute changes in posture, especially between an upright and a
      head-down position, may cause acute posterior vitreous detachment. As yoga
      practitioners may be required to assume this head-down position, myopic patients
      should be warned of the possible ocular complications of this exercise.

PMID- 29581922
TI  - A Lymphoma Almost Overlooked.
AB  - A 50-year-old female with a prolonged history of untreated human immunodeficiency
      virus (HIV) presented with a large vaginal mass. During workup, the mass was
      found to be vaginal squamous cell carcinoma. Imaging suggested stage IV disease,
      but a biopsy of liver lesions demonstrated synchronous diffuse large B-cell
      lymphoma. Her treatment course was notable for complete remission of her lymphoma
      with lymphoma-directed chemotherapy and complete clinical response of her
      squamous cell carcinoma to lymphoma-directed therapy. She tolerated intensive
      chemotherapy despite her HIV but eventually died due to infectious complications
      during surgery to address a vaginal fistula. The case is demonstrative of several
      important diagnostic and therapeutic principles in the management of HIV
      associated malignancies. Thorough consideration and testing must be performed to
      ensure accurate staging, as synchronous malignancies and infections can distort
      standard clinical testing. Further, standard chemotherapeutic regimens often must
      be tailored and specially sequenced when dealing with severely immunocompromised
      patients with multiple synchronous processes.

PMID- 29581923
TI  - Existing Smog in Lahore, Pakistan: An Alarming Public Health Concern.
AB  - Lahore, the second-largest and most polluted city in Pakistan, has been plagued
      by a heavy blanket of smog recently. The ever-growing urbanization and
      industrialization have contributed to the worsening air quality of the city.
      Smog, being hazardous to health, is leading to a rapid sprout in multiple health
      related problems, as well as raising concerns about the long-term deleterious
      effects on public health. The current situation is expected to worsen due to the
      lack of an active action plan from the government's side and a failure of
      concerned authorities to take note of the urgency of the situation. Hence, we aim
      to highlight this pressing issue in the light of previously published articles,
      to alert the relevant authorities regarding the detrimental consequences smog can
      have on public health and urge them to take immediate action to avoid further
      damage.

PMID- 29581924
TI  - Distinguishing Pediatric Lyme Arthritis of the Hip from Transient Synovitis and
      Acute Bacterial Septic Arthritis: A Systematic Review and Meta-analysis.
AB  - Objective Lyme arthritis is an increasingly recognized clinical entity that often
      prompts orthopaedic evaluation in pediatric patients. While Lyme arthritis is
      most common in the knee, the clinical presentation of Lyme arthritis of the hip
      can be similar to both acute bacterial septic arthritis and transient synovitis.
      Accurately distinguishing these clinical entities is important since the
      definitive treatment of each is distinct. Because there is limited literature on
      monoarticular Lyme arthritis of the hip, the purpose of this study was to perform
      a systematic review and meta-analysis of clinical and laboratory parameters
      associated with Lyme arthritis (LA) of the hip and compare them to septic
      arthritis (SA) and transient synovitis (TS).  Study design A systematic review of
      the literature was performed using the following search terms, including the
      variants and plural counterparts "hip" and "Lyme arthritis." A final database of
      individual patients was assembled from the published literature and direct author
      correspondence, when available. A previously published cohort of patients with
      hip transient synovitis or septic arthritis was used for comparative analysis. A
      comparative statistical analysis was performed to the assembled database to
      assess differences in laboratory and clinical variables between the three
      diagnoses.  Results Data on 88 patients diagnosed with Lyme arthritis of the hip
      was collected and consolidated from the 12 articles meeting inclusion criteria.
      The average age of patients presenting with Lyme arthritis was 7.5 years (+/- 3.5
      years), the mean erythrocyte sedimentation rate (ESR), and the C-reactive protein
      (CRP) was 41 mm/hr and 3.9 mg/L, respectively. Peripheral white blood cell (WBC)
      count averaged 10.6 x 109cells/L with the synovial WBC count averaging 55,888
      cells/mm3. Compared to a previous cohort of patients with confirmed transient
      synovitis or septic arthritis, the 95% confidence interval for ESR was 21 - 33
      mm/hr in those diagnosed with toxic synovitis (TS), 37 - 46 mm/hr for Lyme
      arthritis (LA), and 44 - 64 mm/hr for septic arthritis (SA). Synovial WBC counts
      (cells/mm3) 95% confidence intervals (CI) were 5,644 - 15,388 cells/mm3 for TS,
      47,533 - 64,242 cells/mm3 for LA, and 105,432 - 260,214 cells/mm3 for SA. There
      was a statistically significant difference in the incidence of fever > 38.5oC (P
      < 0.001) and refusal to bear weight (P < 0.01) between SA, LA, and TS.
      Conclusions Monoarticular Lyme arthritis can be a cause of hip pain in certain
      geographic areas and has clinical and diagnostic overlap with transient synovitis
      and acute bacterial septic arthritis. This study consolidates the available
      literature and represents the largest series of patients diagnosed with Lyme
      arthritis of the hip to date. We propose a diagnostic algorithm that serially
      incorporates ESR, followed by a synovial neutrophil count, when evaluating
      pediatric patients with an irritable hip in Lyme endemic areas.

PMID- 29581925
TI  - Isolated Renal Laceration on Point-of-care Ultrasound.
AB  - We report a renal laceration identified on a point-of-care ultrasound (POCUS)
      performed in the emergency department on a 58-year-old female presenting after
      blunt trauma. Emergency workup demonstrated a right flank abrasion with
      tenderness to palpation, hematuria, and decreasing hematocrit. A Focused
      Assessment with Sonography in Trauma (FAST) exam, performed as part of the intake
      trauma protocol, identified positive intraperitoneal fluid in the right upper
      quadrant. A computed tomography (CT) scan established a diagnosis of isolated
      right renal hematoma arising from a Grade IV laceration, with no collecting duct
      involvement. This report reviews the sonographic distinction between a renal
      hematoma and a positive FAST exam, and emphasizes the vital role ultrasound plays
      in the evaluation of the trauma patient.

PMID- 29581926
TI  - Morphine, Oxygen, Nitrates, and Mortality Reducing Pharmacological Treatment for
      Acute Coronary Syndrome: An Evidence-based Review.
AB  - Since it was first reported in 1912, acute coronary syndrome (ACS) has become the
      leading cause of death in the Western world. Several improvements that have been
      made over the years in the pharmacological treatment of ACS have reduced the
      relative risk of death due to myocardial infarction from 35-45% previously to
      approximately 3.5% at present. Universities, websites, and educational videos
      commonly use a mnemonic for morphine, oxygen, nitrates, and aspirin (MONA) to
      refer to the adjuvant treatment used for the management of ACS. We review the
      scientific data pertaining to treatment strategies for the management of ACS and
      discuss whether MONA remains relevant in the present scenario. While using
      morphine and oxygen is associated with risks such as higher mortality and
      increase in the size of the infarct, respectively, several available drugs such
      as fibrinolytics, anticoagulants, beta-blockers, renin-angiotensin-aldosterone
      system inhibitors, P2Y12 inhibitors, and statins are known to be useful to treat
      ACS. MONA should be viewed as an obsolete teaching and learning aid, and
      therefore we recommend that its use be discontinued for the management of ACS.

PMID- 29581929
TI  - An efficient method for integration of PCR fragments into adjacent or overlapping
      restriction sites during gene cloning.
AB  - In the present work, a simple and straightforward method was developed to clone
      any PCR-amplified products into restriction sites that are very close, adjacent
      or overlapping in the expression vector. The novelty of the methodology involves
      a crucial primer-designing step by adding appropriate overhangs to the 5' ends of
      primers based on the multiple cloning sites (MCS) (polylinker) region of
      expression vector. After PCR amplification, actual cloning is performed not in
      adjacent RE sites, but in sites that are little distant in the MCS. However, the
      sites lost during this cloning step are maintained intact since they are provided
      by the cloned PCR product (through the primer overhangs). Gene for green
      fluorescent protein (GFP) was cloned and expressed employing this strategy to
      demonstrate its simplicity. This method is highly useful for vector modification
      without losing the restriction sites present in the MCS.

PMID- 29581927
TI  - Differential gene expression profiling through transcriptome approach of
      Saccharum spontaneum L. under low temperature stress reveals genes potentially
      involved in cold acclimation.
AB  - Sugarcane (Saccharum sp.) is predominantly grown in both tropics and subtropics
      in India, and the subtropics alone contribute more than half of sugarcane
      production. Sugarcane active growth period in subtropics is restricted to 8-9
      months mainly due to winter's low temperature stress prevailing during November
      to February every year. Being a commercial crop, tolerance to low temperature is
      important in sugarcane improvement programs. Development of cold tolerant
      sugarcane varieties require a deep knowledge on molecular mechanism naturally
      adapted by cold tolerant genotypes during low temperature stress. To understand
      gene regulation under low temperature stress, control and stressed (10  degrees
      C, 24 h) leaf samples of cold tolerant S. spontaneum IND 00-1037 collected from
      high altitude region in Arunachal Pradesh were used for transcriptome analysis
      using the Illumina NextSeq 500 platform with paired-end sequencing method. Raw
      reads of 5.1 GB (control) and 5.3 GB (stressed) obtained were assembled using
      trinity and annotated with UNIPROT, KEGG, GO, COG and SUCEST databases, and
      transcriptome was validated using qRT-PCR. The differential gene expression (DGE)
      analysis showed that 2583 genes were upregulated and 3302 genes were down
      regulated upon low temperature stress. A total of 170 cold responsive
      transcriptional factors belonging to 30 families were differentially regulated.
      CBF6 (C-binding factor), a DNA binding transcriptional activation protein
      associated with cold acclimation and freezing tolerance was differentially
      upregulated. Many low temperature responsive genes involved in various metabolic
      pathways, viz. cold sensing through membrane fluidity, calcium and lipid
      signaling genes, MAP kinases, phytohormone signaling and biosynthetic genes,
      antioxidative enzymes, membrane and cellular stabilizing genes, genes involved in
      biosynthesis of polyunsaturated fatty acids, chaperones, LEA proteins, soluble
      sugars, osmoprotectants, lignin and pectin biosynthetic genes were also
      differentially upregulated. Potential cold responsive genes and transcriptional
      factors involved in cold tolerance mechanism in cold tolerant S. spontaneum IND
      00-1037 were identified. Together, this study provides insights into the cold
      tolerance to low temperature stress in S. spontaneum, thus opening applications
      in the genetic improvement of cold stress tolerance in sugarcane.

PMID- 29581930
TI  - An improved method for rapid analysis of promoters using modified sonication
      assisted transient assay.
AB  - We present here a modified, sonication-assisted transient transformation assay
      for rapid analysis of cis-regulatory elements. We tested promoter elements from
      MIR159B locus of Brassica juncea by generating stable transgenic lines and
      compared the transcriptional activity of GUS reporter with that of the transient
      assay method. To obtain reliable and repeatable results, and to omit false
      positive data, we optimized several parameters including sonication duration and
      cycle and concentration of Agrobacterium tumefaciens measured as optical density
      (O.D.) at 600 nm. To the best of our knowledge, this is the first report of
      promoter characterization of MIR159B from Brassica juncea, and comparative
      analysis of stable and transient lines. Our analysis shows that the protocol
      described herein allows understanding promoter activity/transcriptional control
      in tissues other than leaf or protoplast which have remained the mainstay for
      transient analysis thus far. We tested reporter gene GUS under the control of
      constitutive promoter, CaMV 35S, and MIR159b from Brassica juncea. We optimized
      the duration of sonication (5-, 10- and 15-min cycle), bacterial density
      (measured as O.D at 600 nm = 0.6/0.8/1.0) and Agro-infection time (5, 10, 15
      min), and co-cultivation (12-, and 24-h). Sonication cycle of 10-min, followed by
      Agro-infection and co-cultivation with Agrobacterium tumefaciens with O.D. 600 nm
      = 0.8 and for 12 h was found to be optimum. We could successfully express
      reporter genes in deep-seated tissues such as floral organs and pollen grains
      where it was previously not possible to perform transient assay. Constitutive GUS
      activity was observed when reporter was placed under control of the constitutive
      promoter of CaMV 35S. Reporter GUS when placed under transcriptional control of
      MIR159b promoter from Brassica juncea showed reporter activity in floral tissues,
      in mature pollen grains. Comparative analysis of reporter activity from stable
      transgenic lines at T2 generation with that of transient assay system reveals
      identical to near-identical reporter activity. Transient assay could be
      successfully performed in tissues collected not only from Arabidopsis thaliana,
      but also from Brassica juncea and Brassica nigra to demonstrate its wide
      applicability. Our modified method thus has the potential of quick and rapid
      analysis of promoter activity and allows us to record the developmental dynamics
      and spatio-temporal expression pattern driven by specific promoters. Suitable
      modification and controls should also allow analysis of hormonal regulation and
      identification of trans-factors via DNA-protein interactions. Furthermore, this
      method can also be extended to study promoters under various environmental
      conditions that otherwise do not allow growth and complete life cycle of healthy
      plants and can be modified to test reporter activity in other non-model plants or
      plants with long life cycle.

PMID- 29581932
TI  - Enhanced antimicrobial, antioxidant and anticancer activity of Rhizophora
      apiculata: An experimental report.
AB  - The present study is designed to evaluate the antimicrobial, antioxidant and
      anticancer activities of Rhizophora apiculata. Initially, the phenolic and
      flavonoid content was quantified in solvent extracts, and gallic acid and rutin
      were used as a control, respectively. Further, antimicrobial and minimal
      inhibitory activities of different solvent extracts were assessed against human
      clinical pathogenic bacteria, and the results showed that butanol and methanol
      extract has potential antimicrobial activity. FTIR analysis of solvent extracts
      showed the presence of phenolic compounds at 3409-3430 cm-1 that actively
      involved in various applications including antioxidant and anticancer activities.
      The in vitro antioxidant activity of solvent extracts showed excellent
      antioxidant potential, about 84% of DPPH free-radical scavenging, 76% of hydrogen
      peroxide, 82% of hydroxyl radical scavenging, and 80% of reducing power. Two-way
      ANOVA analysis showed that the highly significant effect of antioxidant activity
      depends on the concentration of extracts. The DNA protection efficiency of
      extracts against oxidative damage was confirmed by DNA nicking assay using
      bacterial DNA. The methanol extract effectively inhibited the growth and induces
      the apoptosis through ROS generation and sensitizes the mitochondrial membrane
      potential of A549 lung cancer cells. Taken together, the results showed that the
      solvent extracts of R. apiculata could be potential antioxidant and anticancer
      agents.

PMID- 29581931
TI  - Pectinolytic enzymes-solid state fermentation, assay methods and applications in
      fruit juice industries: a review.
AB  - A plethora of solid substrates, cultivation conditions and enzyme assay methods
      have been used for efficient production and estimation of polygalacturonase and
      pectin methylesterase enzymes. Recent developments in industrial biotechnology
      offer several opportunities for the utilization of low cost agro-industrial waste
      in Solid State Fermentation (SSF) for the pectinolytic enzyme production using
      fungi. Fruit waste mainly citrus fruit waste alone and along with other agro
      industrial waste has been explored in SSF for enzyme production. Agro-industrial
      waste, due to the economic advantage of low procuring cost has been employed in
      SSF bioreactors for pectinolytic enzyme production. Acidic pectinases produced by
      fungi are utilized especially in food industries for clarification of fruit
      juices. This review focuses on the recent developments in SSF processes utilizing
      agro-industrial residues for polygalacturonase and pectin methylesterase
      production, their various assay methods and applications in fruit juice
      industries.

PMID- 29581933
TI  - Cervical Stenosis in Adult Arthrogryposis: A Case Report and Review of the
      Literature.
AB  - Arthrogryposis multiplex congenita is a rare, nonprogressive congenital disorder
      that describes a constellation of conditions characterized by multiple joint
      contractures. Spinal pathology and deformity are common; however, the majority of
      the literature on arthrogryposis is focused on pediatric management. There exist
      very few reports on long-term outcomes and management of adults with
      arthrogryposis. We present a case of cervical spinal stenosis in an adult female
      with arthrogryposis that underwent posterior cervical decompression and fusion. A
      review of spine-related sequelae seen in adults with arthrogryposis and
      considerations for spinal surgery for these patients is discussed.

PMID- 29581935
TI  - Xpert implementation in challenging scenarios: a brand-new car running on the
      same bumpy old roads.

PMID- 29581934
TI  - The Developmental Nature of the Victim-Offender Overlap.
AB  - Purpose: It is well-established that victims and offenders are often the same
      people, a phenomenon known as the victim-offender overlap, but the developmental
      nature of this overlap remains uncertain. In this study, we drew from a
      developmental theoretical framework to test effects of genetics, individual
      characteristics, and routine-activity-based risks. Drawing from developmental
      literature, we additionally tested the effect of an accumulation of adverse
      childhood experiences (ACEs). Methods: Data came from the Environmental Risk (E
      Risk) Study, a representative UK birth cohort of 2232 twins born in 1994-1995 and
      followed to age 18 (with 93% retention). Crime victimization and offending were
      assessed through self-reports at age 18 (but findings replicated using crime
      records). We used the classical twin study method to decompose variance in the
      victim-offender overlap into genetic and environmental components. We used
      logistic regression to test the effects of childhood risk factors. Results: In
      contrast to past twin studies, we found that environment (as well as genes)
      contributed to the victim-offender overlap. Our logistic regression results
      showed that childhood low self-control and childhood antisocial behavior nearly
      doubled the odds of becoming a victim-offender, compared to a victim-only or an
      offender-only. Each additional ACE increased the odds of becoming a victim
      offender, compared to a victim-only or an offender-only, by approximately 12%,
      pointing to the importance of cumulative childhood adversity. Conclusions: This
      study showed that the victim-offender overlap is, at least partially,
      developmental in nature and predictable from personal childhood characteristics
      and an accumulation of many adverse childhood experiences.

PMID- 29581936
TI  - Unsuccessful Xpert(r) MTB/RIF results: the Nigerian experience.
AB  - Setting: Nigeria, a high tuberculosis (TB) burden country. Objective: To study
      the rate, distribution and causes of unsuccessful Xpert(r) MTB/RIF test outcomes,
      with the aim of identifying key areas that need to be strengthened for optimal
      performance of the assay. Design: This was a retrospective analysis of data
      uploaded between January and December 2015 from Xpert facilities to the central
      server using GXAlert. Result: Of 52 219 test results uploaded from 176 Xpert
      machines, 22.5% were positive for Mycobacterium tuberculosis, 10.8% of which were
      rifampicin-resistant; 4.7% of the total number of results were invalid, 4.2% had
      error results and 2.1% no result outcomes. Technical errors were most frequent
      (69%); these were non-seasonal and occurred in all geopolitical regions and at
      all health facility levels. Temperature-related errors were more prevalent in the
      North-West Region, with peaks in April to June. Peak periods for temperature and
      machine malfunction errors coincided with the periods of low utilisation of the
      assay. Conclusion: The key challenge affecting performance was poor adherence to
      standard operating procedures. Periodic refresher training courses, regular
      supervision, preventive maintenance of Xpert machines and proper storage of
      cartridges are strategies that could improve Xpert performance.

PMID- 29581937
TI  - The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of
      state and local programs.
AB  - Background: The US Centers for Disease Control and Prevention recommend expert
      consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the
      California MDR-TB Service was created to provide expert MDR-TB consultations. We
      describe the characteristics, treatment outcomes and management of patients
      referred to the Service. Methods: Surveillance data were used for descriptive
      analysis of cases, with consultation during July 2002-December 2012. Clinical
      consultation data and modified World Health Organization indicators were used to
      assess the care and management of cases, with consultation from January 2009 to
      December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The
      proportion of patients receiving a consultation increased from 12% in 2002 to 63%
      in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with
      extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5
      (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due
      to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that
      86% underwent rapid molecular drug susceptibility testing, 98% received at least
      four drugs to which they had known or presumed susceptibility, and 93% culture
      converted within 6 months. Conclusions: Consultations with the MDR-TB Service
      increased over time. Results highlight successful treatment and indicator
      outcomes.

PMID- 29581938
TI  - Did diabetes mellitus affect treatment outcome in drug-resistant tuberculosis
      patients in Pakistan from 2010 to 2014?
AB  - Settings: All hospitals managing drug-resistant tuberculosis (DR-TB) according to
      national guidelines in Pakistan. Objectives: To assess the effect of diabetes
      mellitus (DM) and factors associated with unfavourable outcomes in DR-TB.
      Methods: A cross-sectional study based on a retrospective record review of
      patients enrolled on DR-TB treatment from 2010 to 2014 in Pakistan. DR-TB data
      reported to Pakistan's National TB Control Programme on a monthly basis were used
      for the study. Result: Among 5811 patients enrolled on second-line drugs, 8.8%
      had DM. Overall, 68.9% had favourable outcomes. No association was found between
      DM and DR-TB treatment outcomes (risk ratio 0.90, 95%CI 0.74-1.05). Unfavourable
      outcomes were more frequent among DR-TB patients with human immunodeficiency
      virus (HIV) co-infection (OR 11.58, 95%CI 2.20-60.72), extensively drug-resistant
      TB patients (OR 5.36, 95%CI 1.00-28.72), patients with exposure to both first
      line and second-line anti-tuberculosis drugs (OR 2.45, 95%CI 1.21-4.97) and those
      with a previous history of treatment in the private sector (OR 1.53, 95%CI 1.16
      2.02). Conclusion: Although there were limitations to correctly measuring DM and
      its management, DM appears not to be a risk factor for unfavourable outcomes in
      DR-TB patients in our study. DR-TB and HIV co-infection, second-line drug
      resistance and history of treatment in the private sector were nevertheless more
      frequently associated with adverse outcomes.

PMID- 29581939
TI  - IPT during HIV treatment in Myanmar: high rates of coverage, completion and drug
      adherence.
AB  - Setting: A southern Myanmar district providing isoniazid preventive therapy (IPT)
      in one of the last countries to formally recommend it as part of human
      immunodeficiency virus (HIV) care. Objective: To assess coverage and adherence
      and the feasibility of IPT scale-up in a routine care setting in Myanmar. Design:
      A retrospective analysis of people living with HIV (PLHIV) screened for
      tuberculosis (TB) and enrolled in IPT over a 3-year period (July 2011-June 2014)
      using clinical databases. Results: Among 3377 patients under HIV care and
      screened for TB, 2740 (81.1%) initiated IPT, with 2651 (96.8%) completing a 6- or
      9-month course of IPT; 83 (3.1%) interrupted treatment for different reasons,
      including loss to follow-up (n = 41), side effects (n = 15) or drug adherence
      issues (n = 9); 6 (0.2%) died. Among the IPT patients, 33 (1.2%) were diagnosed
      with TB, including 9 (0.3%) while on IPT and 24 (0.9%) within 1 year of
      completion of therapy. Among the PLHIV who completed IPT, one case of isoniazid
      resistance was detected. Conclusion: Scaling up IPT in Myanmar HIV settings is
      feasible with high rates of drug adherence and completion, and a low rate of
      discontinuation due to side effects. IPT scale-up should be prioritised in HIV
      clinical settings in Myanmar.

PMID- 29581941
TI  - Can ventilation oust tuberculosis bacilli? Dare to plug the unpluggable.

PMID- 29581940
TI  - Training social workers to enhance patient-centered care for drug-resistant TB
      HIV in South Africa.
AB  - KwaZulu-Natal, South Africa, is the epicenter of an epidemic of drug-resistant
      tuberculosis (DR-TB) and human immunodeficiency virus (HIV) co-infection,
      characterized by low rates of medication adherence and retention in care. Social
      workers may have a unique role to play in improving DR-TB-HIV outcomes. We
      designed, implemented and evaluated a model-based pilot training course on
      patient-centered care, treatment literacy in DR-TB and HIV coinfection, patient
      support group facilitation, and self-care. Ten social workers participated in a 1
      day training course. Post-training questionnaire scores showed significant
      overall gains (P = 0.003). A brief training intervention may be a useful and
      feasible way to engage social workers in patient-centered care for DR-TB and HIV
      coinfection.

PMID- 29581942
TI  - mHealth to enhance TB referrals: challenge in scaling up.

PMID- 29581943
TI  - mHealth to enhance TB referrals: challenge in scaling up. In reply.

PMID- 29581944
TI  - Osseous changes in the temporomandibular joint in rheumatoid arthritis: A cone
      beam computed tomography study.
AB  - Purpose: To evaluate osseous changes of temporomandibular joint (TMJ) in patients
      with rheumatoid arthritis (RA) using cone-beam computed tomography (CBCT) and to
      correlate the imaging findings with the severity of TMJ dysfunction, clinical
      findings, and laboratory findings. Materials and Methods: This study consisted of
      28 subjects, including 14 RA patients and 14 controls, who were scheduled to
      undergo CBCT imaging for the diagnosis of a complaint not related to or affecting
      the TMJ. The Fonseca's questionnaire was used to assess the severity of TMJ
      dysfunction. Rheumatoid factor (RF) and the erythrocyte sedimentation rate (ESR)
      were assessed in the RA patients. CBCT was then performed in all subjects and
      osseous TMJ abnormalities were assessed. Results: According to the Fonseca's
      questionnaire, 14.3% of the patients had no TMJ dysfunction, while 50%, 21.4%,
      and 14.3% had mild, moderate, and severe dysfunction, respectively. RF was
      positive in 64.3% of patients, and the ESR level was high in 100%. Imaging
      findings revealed a statistically significantly higher prevalence of erosion
      (85.7%), flattening (89.3%), osteophyte formation (32.1%), subchondral cyst
      (32.1%), sclerosis (64.3%), and condylar irregularities (28.6%) in the RA
      patients than in the controls. No correlations were found between CBCT findings
      and the clinical findings, the severity of TMJ dysfunction, disease duration, or
      laboratory results. Conclusion: RA patients might show extensive osseous
      abnormalities with no/mild clinical signs or symptoms of TMJ dysfunction that
      necessitate TMJ imaging for these patients. CBCT is a valuable and efficient
      modality that can assess osseous TMJ changes in RA patients.

PMID- 29581945
TI  - Diagnostic accuracy of cone-beam computed tomography scans with high- and low
      resolution modes for the detection of root perforations.
AB  - Purpose: This study compared the diagnostic accuracy of cone-beam computed
      tomography (CBCT) scans obtained with 2 CBCT systems with high- and low
      resolution modes for the detection of root perforations in endodontically treated
      mandibular molars. Materials and Methods: The root canals of 72 mandibular molars
      were cleaned and shaped. Perforations measuring 0.2, 0.3, and 0.4 mm in diameter
      were created at the furcation area of 48 roots, simulating strip perforations, or
      on the external surfaces of 48 roots, simulating root perforations. Forty-eight
      roots remained intact (control group). The roots were filled using gutta-percha
      (Gapadent, Tianjin, China) and AH26 sealer (Dentsply Maillefer, Ballaigues,
      Switzerland). The CBCT scans were obtained using the NewTom 3G (QR srl, Verona,
      Italy) and Cranex 3D (Soredex, Helsinki, Finland) CBCT systems in high- and low
      resolution modes, and were evaluated by 2 observers. The chi-square test was used
      to assess the nominal variables. Results: In strip perforations, the accuracies
      of low- and high-resolution modes were 75% and 83% for NewTom 3G and 67% and 69%
      for Cranex 3D. In root perforations, the accuracies of low- and high-resolution
      modes were 79% and 83% for NewTom 3G and was 56% and 73% for Cranex 3D.
      Conclusion: The accuracy of the 2 CBCT systems was different for the detection of
      strip and root perforations. The Cranex 3D had non-significantly higher accuracy
      than the NewTom 3G. In both scanners, the high-resolution mode yielded
      significantly higher accuracy than the low-resolution mode. The diagnostic
      accuracy of CBCT scans was not affected by the perforation diameter.

PMID- 29581946
TI  - Estimation of the effective dose of dental cone-beam computed tomography using
      personal computer-based Monte Carlo software.
AB  - Purpose: To calculate the effective doses of cone-beam computed tomography (CBCT)
      using personal computer-based Monte Carlo (PCXMC) software (Radiation and Nuclear
      Safety Authority, Helsinki, Finland) and to compare the calculated effective
      doses with those measured using thermoluminescent dosimeters (TLDs) and an
      anthropomorphic phantom. Materials and Methods: An Alphard VEGA CBCT scanner
      (Asahi Roentgen Ind. Co., Kyoto, Japan) with multiple fields of view (FOVs) was
      used for this study. The effective doses of the scout and main projections of
      CBCT using 1 large and 2 medium FOVs with a height >10 cm were calculated using
      PCXMC and PCXMCRotation software and then were compared with the doses obtained
      using TLD-100 LiF and an anthropomorphic adult human male phantom. Furthermore,
      it was described how to determine the reference points on the Y- and Z-axes in
      PCXMC, the important dose-determining factors in this software. Results: The
      effective doses at CBCT for 1 large (20.0 cm*17.9 cm) and 2 medium FOVs (15.4
      cm*15.4 cm and 10.2 cm*10.2 cm) calculated by the PCXMC software were 181, 300,
      and 158 uSv, respectively. These values were comparable (16%-18% smaller) to
      those obtained through TLD measurements in each mode. Conclusion: The use of
      PCXMC software could be an alternative to the TLD measurement method for
      effective dose estimation in CBCT with large and medium FOVs.

PMID- 29581947
TI  - Effect of field-of-view size on gray values derived from cone-beam computed
      tomography compared with the Hounsfield unit values from multidetector computed
      tomography scans.
AB  - Purpose: This study aimed to evaluate the effect of field-of-view (FOV) size on
      the gray values derived from conebeam computed tomography (CBCT) compared with
      the Hounsfield unit values from multidetector computed tomography (MDCT) scans as
      the gold standard. Materials and Methods: A radiographic phantom was designed
      with 4 acrylic cylinders. One cylinder was filled with distilled water, and the
      other 3 were filled with 3 types of bone substitute: namely, Nanobone, Cenobone,
      and Cerabone. The phantom was scanned with 2 CBCT systems using 2 different FOV
      sizes, and 1 MDCT system was used as the gold standard. The mean gray values
      (MGVs) of each cylinder were calculated in each imaging protocol. Results: In
      both CBCT systems, significant differences were noted in the MGVs of all
      materials between the 2 FOV sizes (P<.05) except for Cerabone in the Cranex3D
      system. Significant differences were found in the MGVs of each material compared
      with the others in both FOV sizes for each CBCT system. No significant difference
      was seen between the Cranex3D CBCT system and the MDCT system in the MGVs of bone
      substitutes on images obtained with a small FOV. Conclusion: The size of the FOV
      significantly changed the MGVs of all bone substitutes, except for Cerabone in
      the Cranex3D system. Both CBCT systems had the ability to distinguish the 3 types
      of bone substitutes based on a comparison of their MGVs. The Cranex3D CBCT system
      used with a small FOV had a significant correlation with MDCT results.

PMID- 29581948
TI  - Metal artifact production and reduction in CBCT with different numbers of basis
      images.
AB  - Purpose: To evaluate the effect of different numbers of basis images and the use
      of metal artifact reduction (MAR) on the production and reduction of artifacts in
      cone-beam computed tomography images. Materials and Methods: An acrylic resin
      phantom with a metal alloy sample was scanned, with 450 or 720 basis images and
      with or without MAR. Standard deviation values for the test areas (around the
      metal object) were obtained as a way of measuring artifact production. Two-way
      analysis of variance was used with a 5% significance level. Results: There was no
      significant difference in artifact production among the images obtained with
      different numbers of basis images without MAR (P=.985). MAR significantly reduced
      artifact production in the test areas only in the protocol using 720 basis images
      (P=.017). The protocol using 450 basis images with MAR showed no significant
      difference in artifact production when compared to the protocol using 720 basis
      images with MAR (P=.579). Conclusion: Protocols with a smaller number of basis
      images and with MAR activated are preferable for minimizing artifact production
      in tomographic images without exposing the patient to a greater radiation dose.

PMID- 29581949
TI  - Strain elastography of tongue carcinoma using intraoral ultrasonography: A
      preliminary study to characterize normal tissues and lesions.
AB  - Purpose: The aim of this study was to evaluate the quantitative strain
      elastography of tongue carcinoma using intraoral ultrasonography. Materials and
      Methods: Two patients with squamous cell carcinoma (SCC) who underwent
      quantitative strain elastography for the diagnosis of tongue lesions using
      intraoral ultrasonography were included in this prospective study. Strain
      elastography was performed using a linear 14 MHz transducer (Aplio 300; Canon
      Medical Systems, Otawara, Japan). Manual light compression and decompression of
      the tongue by the transducer was performed to achieve optimal and consistent
      color coding. The variation in tissue strain over time caused by the compression
      exerted using the probe was displayed as a strain graph. The integrated strain
      elastography software allowed the operator to place circular regions of interest
      (ROIs) of various diameters within the elastography window, and automatically
      displayed quantitative strain (%) for each ROI. Quantitative indices of the
      strain (%) were measured for normal tissues and lesions in the tongue. Results:
      The average strain of normal tissue and tongue SCC in a 50-year-old man was
      1.468% and 0.000%, respectively. The average strain of normal tissue and tongue
      SCC in a 59-year-old man was 1.007% and 0.000%, respectively. Conclusion: We
      investigated the quantitative strain elastography of tongue carcinoma using
      intraoral ultrasonography. Strain elastography using intraoral ultrasonography is
      a promising technique for characterizing and differentiating normal tissues and
      SCC in the tongue.

PMID- 29581950
TI  - Quantitative evaluation of palatal bone thickness in patients with normal and
      open vertical skeletal configurations using cone-beam computed tomography.
AB  - Purpose: To perform a comparative analysis of the palatal bone thickness in Thai
      patients exhibiting class I malocclusion according to whether they exhibited a
      normal or open vertical skeletal configuration using cone-beam computed
      tomography (CBCT). Materials and Methods: Thirty CBCT images of Thai orthodontic
      patients (15-30 years of age) exhibiting class I malocclusion with a normal or
      open vertical skeletal configuration were selected. Palatal bone thickness was
      measured in a 3.0-mm grid pattern on both the right and left sides. The palatal
      bone thickness of the normal-bite and open-bite groups was compared using the
      independent t-test. The level of significance was established at P<.05. Results:
      The palatal bone thickness in the normal-bite group ranged from 2.2+/-1.0 mm to
      12.6+/-4.1 mm. The palatal bone thickness in the open-bite group ranged from
      1.9+/-1.1 mm to 13.2+/-2.3 mm. The palatal bone thickness was lower at almost all
      sites in patients with open bite than in those with normal bite. Significant
      differences were found at almost all anteroposterior sites along the 3 most
      medial sections (3.0, 6.0, and 9.0 mm lateral to the midsagittal plane) (P<.05).
      Conclusion: Class I malocclusion with open vertical skeletal configuration may
      affect palatal bone thickness, so the placement of temporary anchorage devices or
      miniscrew implants in the palatal area in such patients should be performed with
      caution.

PMID- 29581951
TI  - Unusual malignant neoplasms occurring around dental implants: A report of 2
      cases.
AB  - Osseointegrated implants are now commonplace in contemporary dentistry. However,
      a number of complications can occur around dental implants, including peri
      implantitis, maxillary sinusitis, osteomyelitis, and neoplasms. There have been
      several reports of a malignant neoplasm occurring adjacent to a dental implant.
      In this report, we describe 2 such cases. One case was that of a 75-year-old man
      with no previous history of malignant disease who developed a solitary
      plasmacytoma around a dental implant in the left posterior mandible, and the
      other was that of a 43-year-old man who was diagnosed with squamous cell
      carcinoma adjacent to a dental implant in the right posterior mandible. Our
      experiences with these 2 cases suggest the possibility of a relationship between
      implant treatment and an inflammatory cofactor that might increase the risk of
      development of a malignant neoplasm.

PMID- 29581952
TI  - Fractured styloid process masquerading as neck pain: Cone-beam computed
      tomography investigation and review of the literature.
AB  - Historically, Eagle syndrome is a term that has been used to describe radiating
      pain in the orofacial region, foreign body sensation, and/or dysphagia due to a
      unilateral or bilateral elongated styloid process impinging upon the tonsillar
      region. Because elongated styloid processes-with or without associated Eagle
      syndrome-can present with various symptoms and radiographic findings, it can be
      challenging for healthcare practitioners to formulate an accurate diagnosis.
      Abnormal styloid anatomy can lead to a multitude of symptoms, including chronic
      orofacial/neck pain, thus masquerading as more commonly diagnosed conditions. In
      this report, we describe a patient who presented to our department with styloid
      process elongation and fracture. A careful history, physical examination, and a
      conebeam computed tomography (CBCT) investigation led to the diagnosis. The
      patient was then referred for appropriate care. This case report demonstrates the
      utilization of CBCT in differentiating a fracture site from a pseudo-joint that
      might mimic a fracture.

PMID- 29581953
TI  - Organized hematoma of temporomandibular joint.
AB  - Organized hematoma is a pseudo-tumorous lesion mostly occurs at sinonasal cavity
      and often confused with malignant neoplasm. The initiation of this lesion is
      blood accumulation, probably due to trauma, and this hematoma develops into
      organized hematoma as it encapsulated with fibrous band and neo-vascularized.
      Since it is uninformed at temporomandibular joint (TMJ) region, imaging diagnosis
      might be challenging. Also, delayed detection of mass involving TMJ is not
      uncommon due to confusion with joint disorder. Thus, this report introduced the
      rare pathology, organized hematoma on TMJ with advanced imaging features. Also,
      diagnostic point for early detection was described for the TMJ tumors and pseudo
      tumors considering complexity of surgical intervention in this region.

PMID- 29581954
TI  - Influence of Altered Gut Microbiota Composition on Aging and Aging-Related
      Diseases.
AB  - The gut microbiota forms a large community that coexists with all species,
      including humans and rodents. Genome projects have been conducted by many
      researchers in nearly every country to better understand and treat diseases that
      lead to death in humans. However, the gut microbiota is known as a "second
      genome" because it includes microbes, genomic DNA, proteins, and metabolites. A
      large number of studies have revealed the importance of the gut microbiota. In
      elderly people, the diversity of the gut microbiota is reduced and there is an
      increased incidence of degenerative diseases, including Alzheimer's and
      Parkinson's, and decreased cognitive and memory functions. However, the
      administration of pre/probiotics can help to improve the symptoms of these
      diseases. Therefore, we believe that the gut microbiota is important for
      maintaining homeostasis and diversity, as well as for avoiding gastrointestinal
      tract-derived diseases and improving health in the elderly population.

PMID- 29581955
TI  - Effects of Sedentary Behavior, Physical Activity, Frequency of Protein
      Consumption, Lower Extremity Strength and Lean Mass on All-Cause Mortality.
AB  - Background: No study has evaluated the potential independent and cumulative
      effects of physical activity, sedentary behavior, daily frequency of protein
      consumption, lean mass and muscular strength on mortality risk. Methods: Data
      from the 1999-2002 NHANES were utilized (N = 1,079 adults 50-85 yr), with follow
      up through 2011. Leg lean mass was estimated from DXA scans. Knee extensor
      strength was assessed using the Kin Com MP dynamometer. Physical activity and
      sedentary behavior were assessed via questionnaire, with the number of meals/day
      of >=30 g of protein/meal assessed via a "multiple pass" 24-hour dietary
      interview. An index score was created (range = 0-5) indicating the number of
      these health characteristics each participant had. Results: Only less sedentary
      behavior was independently associated with reduced mortality risk (HRadjustment =
      0.46; 0.32-0.66). After adjustments, and compared to those with an index score of
      0, those with an index score of 1, 2 and 3+, respectively, had a 34%, 49%, and
      57% reduced risk of all-cause mortality. Conclusion: While considering physical
      activity, sedentary behavior, daily protein frequency consumption, lean mass and
      muscular strength, only sedentary behavior was independently associated with
      mortality risk among older adults.

PMID- 29581956
TI  - Effects of Lifestyle on Muscle Strength in a Healthy Danish Population.
AB  - Background: Lifestyle is expected to influence muscle strength. This study aimed
      at assessing a possible relationship between smoking, alcohol intake and physical
      activity, and muscle strength in a healthy Danish population aged 20-79 years.
      Population study based on data collected from The Copenhagen City Heart Study
      (CCHS) and measurements of Isokinetic muscle strength from a sub-study of
      randomly selected healthy participants from CCHS. Methods: 126 women and 63 men
      were studied. All participants completed a questionnaire regarding their
      lifestyle, including physical activity, alcohol intake and smoking habits.
      Isokinetic muscle strength was measured over the upper extremities (UE), trunk,
      and lower extremities (LE). Multivariate analyses including all of the variables
      were carried out. Results: The level of daily physical activity during leisure
      was positively correlated to muscle strength in the lower extremities (p = 0.03)
      for women, and lower extremities (p = 0.03) and trunk (p = 0.007) for men.
      Alcohol Intake was in general not correlated to muscle strength. No clear effect
      of smoking was seen on muscle strength. Conclusion: Our results show that
      physical activity during leisure is associated with a positive effect on muscle
      strength in both sexes. When keeping alcohol intake within the recommended
      limits, alcohol does not seem to affect muscle strength negatively. No effect of
      smoking on muscle strength was found in our group of healthy subjects. The
      findings are of importance when considering recommendation on life style when
      wishing to keeping fit with age to be able to carry out daily activities.

PMID- 29581957
TI  - Impact of Spiritual Behavior on Self-Reported Illness: A Cross-Sectional Study
      among Women in the Kailali District of Nepal.
AB  - Background: Different health behaviors influence health and illness. Spiritual
      well-being is one of the most important aspects of health promotion. The aim of
      this study was to identify the association between spiritual behavior in relation
      to meditation, worship, and physical exercise during yoga with self-reported
      disease/illness among women of the Kailali district of Nepal. Methods: This was a
      cross-sectional study with 453 randomly selected women in the Kailali district of
      Nepal within 1 municipality and 4 village development committees (VDC) using
      cluster sampling. We used a semi-structured interview to collect the data for
      selected respondents. Socioeconomics, lifestyle, self-care, and spiritual
      behavior variables were independent variables, and self-reported illness in the
      past year was a dependent variable. Descriptive statistics, chi square,
      hierarchical logistic regression for odds ratio, and 95% CI were used when
      appropriate. Results: Study results showed that 89% of participants were from the
      rural area, 29.3% were housewives, 51.4% had no formal education, 43.2% used
      tobacco, 42.1% did yoga, and 16.9% engaged in regular worship. Self-reported
      illness was associated with safe toilet-using behavior, tobacco use, junk food
      consumption, yoga and regular exercise, worship, and regular sleeping habits.
      Comparing odds ratios and 95% CIs, the women who had safe toilet behavior and did
      not use tobacco were 2.48 (1.98-7.98) and 2.86 (1.74-7.34) times less likely to
      be ill, respectively. Likewise, women who consumed junk food; did not regularly
      exercise, meditate, or worship; and had irregular sleeping habits were 1.65 (1.32
      4.61), 2.81(1.91-5.62), 2.56 (2.01-4.88), 4.56 (3.91-8.26), and 2.45 (2.12-5.03)
      times more likely to become ill, respectively. Conclusion: Our study concludes
      that spiritual behavior is effective for better health and low risk for disease
      occurrence. A spiritual health policy and separate curriculum for basic education
      and medical education should be promoted globally, and further research is
      recommended.

PMID- 29581958
TI  - Effects of Different Types of Smoking Cessation Treatments for South Korean Adult
      Smokers without an Intention to Quit.
AB  - Background: While there are many different ways to quit smoking, current methods
      are not equally successful. The objective of this study was to analyze the
      effects of different types of stop smoking treatment for South Korean adult
      smokers without an intention to quit. Methods: This cross-sectional study used
      data of 14,174 adults (age 19 years and over) from the Korea national health and
      nutrition examination survey (2007-2012) who have experience of smoking. The data
      were analyzed using multiple logistic regression. Results: According to multiple
      logistic regression analysis, the education and counseling plus prescription drug
      group (OR = 14.831, 95% CI = 1.256 to 175.136) and education and counseling plus
      NRT group (OR = 3.060, 95% CI = 1.971 to 4.748) were associated with increased
      odds of quitting success compared to the no intervention group. Second, the
      education and counseling group was associated with increased odds of quitting
      success compared to the no intervention group (OR = 4.944, 95% CI = 3.463 to
      7.058). Third, education and counseling plus NRT (OR = 0.325, 95% CI = 0.161 to
      0.657) and NRT alone (OR = 0.322, 95% CI = 0.175 to 0.593) were associated with
      decreased odds of quitting success compared to the group using prescription drug
      only. Conclusion: These findings suggest that an approach utilizing education and
      counseling plus prescription drugs is the most successful type of stop smoking
      treatment for South Korean adult smokers without an intention to quit.

PMID- 29581959
TI  - Sleep Quality and Nutritional Intake in Subjects with Sleep Issues According to
      Perceived Stress Levels.
AB  - Background: Sleep disorders can negatively affect quality of life with reduced
      cognitive function. Since stress and eating behavior are considered crucial
      factors for sleep, this study's aim was to compare objective quality of sleep and
      nutrition between subjects with sleep issues and different stress levels.
      Methods: The investigation was performed in adults (>=18 years old) in the Sleep
      Laboratory between September 2015 and February 2016. Several measurement
      instruments were utilized, including the Pittsburgh Sleep Quality Index (PSQI),
      the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K),
      polysomnography, and a food frequency questionnaire (FFQ). Results: There were no
      statistical differences in demographic data between the lower and higher stress
      groups except age, which was adjusted. Sleep quality in the lower stress group
      was better than the higher stress group in terms of sleep efficiency (90.92 +/-
      7.72 vs 85.36 +/- 10.25%), sleep latency (16.94 +/- 20.86 vs 9.42 +/- 8.24 min),
      and WASO result (26 +/- 26.13 vs 43.66 +/- 41.32 min). There were statistically
      significant differences in nutritional intake between the groups: the lower
      stress group consumed more vegetables than the higher stress group while the
      higher stress group consumed more grains, meat and eggs, soju, and coffee
      products than the lower stress group. Conclusion: This study found that stress
      level and food intake have significant associations with objective sleep quality.
      Food and stress management for insomnia should be considered for improving not
      only quantity but also quality of sleep.

PMID- 29581960
TI  - Identification of Wheat Inflorescence Development-Related Genes Using a
      Comparative Transcriptomics Approach.
AB  - Inflorescence represents the highly specialized plant tissue producing the
      grains. Although key genes regulating flower initiation and development are
      conserved, the mechanism regulating fertility is still not well explained. To
      identify genes and gene network underlying inflorescence morphology and fertility
      of bread wheat, expressed sequence tags (ESTs) from different tissues were
      analyzed using a comparative transcriptomics approach. Based on statistical
      comparison of EST frequencies of individual genes in EST pools representing
      different tissues and verification with RT-PCR and RNA-seq data, 170 genes of 59
      gene sets predominantly expressed in the inflorescence were obtained. Nearly one
      third of the gene sets displayed differentiated expression profiles in terms of
      their subgenome orthologs. The identified genes, most of which were predominantly
      expressed in anthers, encode proteins involved in wheat floral identity
      determination, anther and pollen development, pollen-pistil interaction, and
      others. Particularly, 25 annotated gene sets are associated with pollen wall
      formation, of which 18 encode enzymes or proteins participating in lipid
      metabolic pathway, including fatty acid omega-hydroxylation, alkane and fatty
      alcohol biosynthesis, and glycerophospholipid metabolism. We showed that the
      comparative transcriptomics approach was effective in identifying genes for
      reproductive development and found that lipid metabolism was particularly active
      in wheat anthers.

PMID- 29581961
TI  - Hospitalization Trends in Adult Patients with COPD and Other Respiratory Diseases
      in Northeast China from 2005 to 2015.
AB  - Chronic obstructive pulmonary disease (COPD), pneumonia, asthma, and lung cancer
      are four common respiratory diseases that impose a substantial economic burden on
      both patients and government in China. The objective of our study is to analyze
      the temporal trends of several clinical tracking metrics for hospitalization
      regarding these diseases. Hospital discharge data of 54 hospitals for the period
      2005-2015 were derived from the Health and Family Planning Commission in
      Northeast China. The age-adjusted rate of discharge for the four respiratory
      diseases increased significantly (COPD, pneumonia, asthma: P trend <  .001; lung
      cancer: P trend =  .046). The mean LOS for the four diseases all showed a
      significant decline (P trend <  .001), whereas the mean charge per stay and
      aggregate charge followed an upward trend over time (P trend <  .001). There was
      a clear upward trend for the readmission rate for asthma patients (P trend = 
      .001), while the trend for COPD patients was unclear (P trend =  .224). Age
      adjusted discharge rates, LOS, and charges for hospitalization regarding several
      common respiratory diseases in China showed different patterns of change over the
      past decade. Our results should aid government and administrators in making
      informed decisions about the management and treatment of respiratory diseases.

PMID- 29581962
TI  - Protein Kinase G Induces an Immune Response in Cows Exposed to Mycobacterium
      avium Subsp. paratuberculosis.
AB  - To establish infection, pathogens secrete virulence factors, such as protein
      kinases and phosphatases, to modulate the signal transduction pathways used by
      host cells to initiate immune response. The protein MAP3893c is annotated in the
      genome sequence of Mycobacterium avium subspecies paratuberculosis (MAP), the
      causative agent of Johne's disease, as the serine/threonine protein kinase G
      (PknG). In this work, we report that PknG is a functional kinase that is secreted
      within macrophages at early stages of infection. The antigen is able to induce an
      immune response from cattle exposed to MAP in the form of interferon gamma
      production after stimulation of whole blood with PknG. These findings suggest
      that PknG may contribute to the pathogenesis of MAP by phosphorylating macrophage
      signalling and/or adaptor molecules as observed with other pathogenic
      mycobacterial species.

PMID- 29581963
TI  - Current Knowledge and Recent Advances of Right Ventricular Molecular Biology and
      Metabolism from Congenital Heart Disease to Chronic Pulmonary Hypertension.
AB  - Studies about pulmonary hypertension and congenital heart diseases have
      introduced the concept of right ventricular remodeling leading these pathologies
      to a similar outcome: right ventricular failure. However right ventricular
      remodeling is also a physiological process that enables the normal fetal right
      ventricle to adapt at birth and gain its adult phenotype. The healthy mature
      right ventricle is exposed to low pulmonary vascular resistances and is
      compliant. However, in the setting of chronic pressure overload, as in pulmonary
      hypertension, or volume overload, as in congenital heart diseases, the right
      ventricle reverts back to a fetal phenotype to sustain its function. Mechanisms
      include angiogenic changes and concomitant increased metabolic activity to
      maintain energy production. Eventually, the remodeled right ventricle cannot
      resist the increased afterload, leading to right ventricular failure. After
      comparing the fetal and adult healthy right ventricles, we sought to review the
      main metabolic and cellular changes occurring in the setting of PH and CHD. Their
      association with RV function and potential impact on clinical practice will also
      be discussed.

PMID- 29581964
TI  - Age Is Not a Limiting Factor in Interventional Radiotherapy (Brachytherapy) for
      Patients with Localized Cancer.
AB  - This review examines the role of interventional radiotherapy (IRT otherwise known
      as brachytherapy) in cancer treatment for elderly patients. Despite their
      advanced age and associated comorbidities, elderly patients should receive
      definitive cancer therapies, including surgery and radiotherapy (RT). In fact, RT
      becomes first-line option for patients who are not eligible for surgery (due to
      comorbidities, anticoagulant drugs, and risk of disfigurement) or those who
      refuse it. It emerged from this review of the literature as effective, simple,
      safe, and comfortable and was associated with good local control, low toxicity
      rates, and excellent cosmesis and provided a cost benefit. IRT may be used as
      sole treatment for small cancers or as a useful adjunct to surgery or external
      beam radiotherapy (EBRT) in more advanced (or lymph node positive) cases,
      especially when the aim is local control with adequate preservation of normal
      tissue function. As palliative treatment, IRT preserves quality of life and/or
      improves survival. It is to be hoped that this review will serve as a helpful
      guide for members of multidisciplinary teams that are involved in treating
      elderly patients with cancer.

PMID- 29581965
TI  - Involvement of Cholinergic Dysfunction and Oxidative Damage in the Effects of
      Simulated Weightlessness on Learning and Memory in Rats.
AB  - The present study aimed to determine how the learning and memory gradually change
      with the prolonged hindlimb unloading (HU) treatment in rats. Different HU
      durations (7 d, 14 d, 21 d, and 28 d) in Sprague-Dawley (SD) rats were
      implemented. Cognitive function was assessed using the Morris water maze (MWM)
      and the shuttle box test. Additionally, parameters about cholinergic activity and
      oxidative stress were tested. Results showed that longer-than-14 d HU led to the
      inferior performances in the behavioral tasks. Besides, acetylcholine esterase
      (AChE) activity, malondialdehyde (MDA) level in brain, reactive oxygen species
      (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG) concentrations of HU rats were
      significantly increased. Furthermore, choline acetyltransferase (ChAT),
      superoxide dismutase (SOD), and catalase (CAT) activity in brain were notably
      attenuated. Most of these effects were more pronounced after longer exposure (21
      d and 28 d) to HU, although some indicators had their own characteristics of
      change. These results indicate that cholinergic dysfunction and oxidative damage
      were involved in the learning and memory impairments induced by longer-than-14 d
      HU. Moreover, the negative effects of HU tend to be augmented as the HU duration
      becomes longer. The results may be helpful to present possible biochemical
      targets for countermeasures development regarding the memory deficits under
      extreme environmental conditions.

PMID- 29581966
TI  - Impaired Gut Epithelial Tight Junction Expression in Hemodialysis Patients
      Complicated with Intradialytic Hypotension.
AB  - Background: There is accumulating evidence pointing to uremia-induced impairment
      of the intestinal epithelial barrier structure in advanced chronic kidney disease
      (CKD) and hemodialysis (HD) patients. In this study, the impact of intradialytic
      hypotension on intestinal barrier integrity is being explored. Methods:
      Immunohistochemical staining was used to detect the expression of 4 types of
      tight junction (TJ) proteins such as occludin, zonula occludens-1 (ZO-1), claudin
      1, and claudin-4, in colonic samples of a group of patients receiving segmental
      colectomy. Five patients with nondialysis CKD (group 2), 5 HD patients with
      intradialytic hypotension (group 3), and 5 non-CKD subjects (group 1) were
      examined. Results: Both patients' groups 2 and 3 demonstrated significantly
      reduced expression of occludin as compared to group 1 (p < 0.05 and p < 0.01,
      resp.). Except for claudin-4, expression of all markers of TJ proteins was
      significantly reduced in patients' group 3 as compared to control (p < 0.01). In
      addition, decreased expressions of claudin-1 and ZO-1 were also more pronounced
      in group 3 when compared to group 2. Conclusions: This study extends the earlier
      finding by demonstrating that dialysis-related hypotension caused even marked
      depletion of the key protein constituents of the epithelial TJ.

PMID- 29581968
TI  - A Risk Stratification Model for Lung Cancer Based on Gene Coexpression Network
      and Deep Learning.
AB  - Risk stratification model for lung cancer with gene expression profile is of
      great interest. Instead of previous models based on individual prognostic genes,
      we aimed to develop a novel system-level risk stratification model for lung
      adenocarcinoma based on gene coexpression network. Using multiple microarray,
      gene coexpression network analysis was performed to identify survival-related
      networks. A deep learning based risk stratification model was constructed with
      representative genes of these networks. The model was validated in two test sets.
      Survival analysis was performed using the output of the model to evaluate whether
      it could predict patients' survival independent of clinicopathological variables.
      Five networks were significantly associated with patients' survival. Considering
      prognostic significance and representativeness, genes of the two survival-related
      networks were selected for input of the model. The output of the model was
      significantly associated with patients' survival in two test sets and training
      set (p < 0.00001, p < 0.0001 and p = 0.02 for training and test sets 1 and 2,
      resp.). In multivariate analyses, the model was associated with patients'
      prognosis independent of other clinicopathological features. Our study presents a
      new perspective on incorporating gene coexpression networks into the gene
      expression signature and clinical application of deep learning in genomic data
      science for prognosis prediction.

PMID- 29581967
TI  - Criterion-Related Validity of a Simple Muscle Strength Test to Assess Whole Body
      Muscle Strength in Chinese Children Aged 10 to 12 Years.
AB  - Objective: To study the criterion-related validity of simple muscle strength test
      (SMST) indicators and assess whole body muscle strength in Chinese children aged
      10 to 12 years old. Methods: Two hundred and forty children were equally divided
      into four groups in different genders and residences. The SMST indicators (hand
      grip, knee bent push-up, back muscle strength, sit-up, leg muscle strength, and
      standing long jump) were tested. We set up the total level of the whole-body
      muscle strength (Ftotal) through testing isokinetic muscle strength of the six
      joints' flexion and extension movements. Pearson correlation analyses were used
      to analyze the correlation between the SMST indicators and the Ftotal. Results:
      (1) Leg muscle strength and back muscle strength demonstrated the highest
      validity scores. Sit-ups, hand grip, and standing long jump demonstrated the
      lowest validity scores. (2) Leg muscle strength had the highest validity for
      males, but back muscle strength had the highest validity for females.
      Conclusions: Back muscle strength and leg muscle strength can give the highest
      validity of assessing whole body muscle strength, and also has higher validity in
      both the urban and rural children. For urban children, but not rural, the knee
      bent push-up also has a high validity indicator.

PMID- 29581969
TI  - Analgesic Effect of Extracorporeal Shock Wave Treatment Combined with Fascial
      Manipulation Theory for Adhesive Capsulitis of the Shoulder: A Retrospective
      Study.
AB  - Objectives: This study aims to explore whether extracorporeal shockwave treatment
      (ESWT) based on the theory of fascial manipulation (FM) at select treatment
      points is superior to traditional local ESWT for pain relief in adhesive
      capsulitis of the shoulder. Methods: Data from patients with adhesive capsulitis
      of the shoulder who received weekly ESWT according to fascial manipulation theory
      (ESWT-FM) or local extracorporeal shockwave treatment (L-ESWT) during a 5-week
      treatment period were evaluated. Pain-on-movement numeric rating scale (p-NRS)
      and range of motion (ROM) testing were performed before the treatment period,
      after the first treatment, and after the fifth treatment. Results: There were
      significant reductions in pain scores in the ESWT-FM group (p < 0.05) after the
      first treatment, and after the fifth treatment, both groups had marked,
      significant improvement (p < 0.05), with a significantly greater reduction in
      pain (p-NRS) in the ESWT-FM group compared to the L-ESWT group (p < 0.05). There
      was no significant difference in terms of ROM in the L-ESWT group, while there
      was slight improvement of forward flexion in the ESWT-FM group after the fifth
      treatment. Conclusions: ESWT-FM provided faster pain relief and slightly more
      notable improvement of function compared with L-ESWT for the patients with
      adhesive capsulitis of shoulder.

PMID- 29581970
TI  - Polymorphisms in the Osteopontin Are Associated with Susceptibility to Ankylosing
      Spondylitis in a Han Chinese Population.
AB  - The aim of this study was to investigate whether osteopontin (OPN) variants are
      associated with susceptibility to ankylosing spondylitis (AS) in a Chinese
      population. Polymorphisms at the 9175th position in exon 7 of OPN and rs17524488
      were genotyped using direct sequencing in 186 unrelated AS patients and 188
      ethnically matched healthy controls. Serum concentration of OPN was measured by
      enzyme-linked immunosorbent assay (ELISA) in all participants. AS patients
      displayed significantly higher OPN serum levels than the controls (P < 001). A
      heterozygous, novel 9175 T>A in exon 7 of the OPN gene was found in this study.
      In healthy controls, subjects carrying the rs17524488 G/G genotype of the OPN
      display significantly higher OPN serum levels than the GG/GG genotype (P < 0.05).
      Plasma OPN level is implicated as an early diagnostic marker of AS. The novel
      9175th- (exon 7) position polymorphism of OPN and rs17524488 were related to
      susceptibility to AS in a Chinese population, the rs17524488 G/G genotype may be
      involved in the pathogenesis of AS, and the precise molecular mechanism
      underlying the influence of OPN polymorphisms on the development of AS remains to
      be determined in the further prospective studies.

PMID- 29581971
TI  - Chemoradiotherapy as Definitive Treatment for Elderly Patients with Head and Neck
      Cancer.
AB  - Background: With the aging population and a rising incidence of squamous cell
      carcinoma of the head and neck (SCCHN), there is an emerging need for developing
      strategies to treat elderly patients. Patients and Methods: We retrospectively
      analyzed 158 patients treated with definitive, concurrent chemoradiotherapy (CRT)
      for SCCHN. Clinicopathological characteristics, acute toxicities, and oncological
      outcomes were compared between patients younger and older than (or of age equal
      to) 65, 70, and 75 years. Results: RT dose, chemotherapy regimen, and total
      chemotherapy dose were balanced between the groups. After a median follow-up of
      29 months, overall survival (OS), progression-free survival (PFS), local control
      rate, and distant metastasis-free survival stratified by age of >=65, >=70, or
      >=75 years revealed no differences. The rate of acute toxicities was also not
      higher for older patients. Worse ECOG performance score (ECOG 2-3) was associated
      with impaired OS (p = 0.004) and PFS (p = 0.048). Conclusion: Definitive
      treatment with CRT for SCCHN is feasible and effective; even in advanced age
      treatment decisions should be made according to general condition and
      comorbidity, rather than calendar age alone.

PMID- 29581972
TI  - Effect of Curcumin-Nanoemulsion Associated with Photodynamic Therapy in Cervical
      Carcinoma Cell Lines.
AB  - Cervical cancer is the fourth cause of cancer death in women. Curcumin has
      antineoplastic properties. Furthermore, curcumin may be used as a
      photosensitizing agent in Photodynamic Therapy. This study aimed to investigate
      the effects of Photodynamic Therapy in cellular viability using curcumin
      nanoemulsion as a photosensitizing drug in cervical carcinoma cell lines. The
      empty nanoemulsion presented very low cytotoxicity in all cell lines analyzed.
      Additionally, the incubation with curcumin-nanoemulsion at 20 MUM of curcumin
      showed more than 80% of cell viability for cell lines. Nanoemulsions were shown
      to be internalized inside cells by fluorescence microscopy and were observed in
      the intracellular environment for up to 36 hours after incubation with cell
      lines. In addition, after the Photodynamic Therapy we observed a high phototoxic
      effect of the curcumin-nanoemulsion with less than 5% of viable cells after
      irradiation. This was accompanied by an increase in caspase-3/caspase-7
      activities after cell treatment with curcumin-nanoemulsion and Photodynamic
      Therapy, suggesting cell death by apoptosis. We conclude that the curcumin
      nanoemulsion formulation behaves as a photosensitizing drug in Photodynamic
      Therapy and shows potential as an alternative treatment to cervical lesions using
      an endoscopic diode fiber laser setup for in situ activation or cavity activation
      using a diffuse fiber delivery system.

PMID- 29581974
TI  - Biomechanical Evaluation of a Novel Apatite-Wollastonite Ceramic Cage Design for
      Lumbar Interbody Fusion: A Finite Element Model Study.
AB  - Objectives: Cage design and material properties play a crucial role in the long
      term results, since interbody fusions using intervertebral cages have become one
      of the basic procedures in spinal surgery. Our aim is to design a novel Apatite
      Wollastonite interbody fusion cage and evaluate its biomechanical behavior in
      silico in a segmental spinal model. Materials and Methods: Mechanical properties
      for the Apatite-Wollastonite bioceramic cages were obtained by fitting finite
      element results to the experimental compression behavior of a cage prototype. The
      prototype was made from hydroxyapatite, pseudowollastonite, and frit by
      sintering. The elastic modulus of the material was found to be 32 GPa. Three
      intact lumbar vertebral segments were modelled with the ANSYS 12.0.1 software and
      this model was modified to simulate a Posterior Lumbar Interbody Fusion. Four
      cage designs in different geometries were analyzed in silico under axial loading,
      flexion, extension, and lateral bending. Results: The K2 design had the best
      overall biomechanical performance for the loads considered. Maximum cage stress
      recorded was 36.7 MPa in compression after a flexion load, which was within the
      biomechanical limits of the cage. Conclusion: Biomechanical analyses suggest that
      K2 bioceramic cage is an optimal design and reveals essential material properties
      for a stable interbody fusion.

PMID- 29581973
TI  - Computational Investigation on the Biomechanical Responses of the Osteocytes to
      the Compressive Stimulus: A Poroelastic Model.
AB  - Osteocytes, the major type of bone cells embedded in the bone matrix and
      surrounded by the lacunar and canalicular system, can serve as biomechanosensors
      and biomechanotranducers of the bone. Theoretical analytical methods have been
      employed to investigate the biomechanical responses of osteocytes in vivo; the
      poroelastic properties have not been taken into consideration in the three
      dimensional (3D) finite element model. In this study, a 3D poroelastic idealized
      finite element model was developed and was used to predict biomechanical
      behaviours (maximal principal strain, pore pressure, and fluid velocity) of the
      osteocyte-lacunar-canalicular system under 150-, 1000-, 3000-, and 5000
      microstrain compressive loads, respectively, representing disuse, physiological,
      overuse, and pathological overload loading stimuli. The highest local strain,
      pore pressure, and fluid velocity were found to be highest at the proximal region
      of cell processes. These data suggest that the strain, pore pressure, and fluid
      velocity of the osteocyte-lacunar-canalicular system increase with the global
      loading and that the poroelastic material property affects the biomechanical
      responses to the compressive stimulus. This new model can be used to predict the
      mechanobiological behaviours of osteocytes under the four different compressive
      loadings and may provide an insight into the mechanisms of mechanosensation and
      mechanotransduction of the bone.

PMID- 29581975
TI  - The Role of Actin Dynamics and Actin-Binding Proteins Expression in Epithelial-to
      Mesenchymal Transition and Its Association with Cancer Progression and Evaluation
      of Possible Therapeutic Targets.
AB  - Metastasis causes death of 90% of cancer patients, so it is the most significant
      issue associated with cancer disease. Thus, it is no surprise that many
      researchers are trying to develop drugs targeting or preventing them. The
      secondary tumour site formation is closely related to phenomena like epithelial
      to-mesenchymal and its reverse, mesenchymal-to-epithelial transition. The change
      of the cells' phenotype to mesenchymal involves the acquisition of migratory
      potential. Cancer cells movement is possible due to the development of invasive
      structures like invadopodia, lamellipodia, and filopodia. These changes are
      dependent on the reorganization of the actin cytoskeleton. In turn, the
      polymerization and depolymerization of actin are controlled by actin-binding
      proteins. In many tumour cells, the actin and actin-associated proteins are
      accumulated in the cell nucleus, suggesting that it may also affect the
      progression of cancer by regulating gene expression. Once the cancer cell reaches
      a new habitat it again acquires epithelial features and thus proliferative
      activity. Targeting of epithelial-to-mesenchymal or/and mesenchymal-to-epithelial
      transitions through regulation of their main components expression may be a
      potential solution to the problem of metastasis. This work focuses on the role of
      these processes in tumour progression and the assessment of therapeutic potential
      of agents targeting them.

PMID- 29581977
TI  - Association between Sleep Apnea Hypopnea Syndrome and the Risk of Atrial
      Fibrillation: A Meta-Analysis of Cohort Study.
AB  - Numerous reports have been done to seek the relationship between sleep apnea
      hypopnea syndrome (SAHS) and the risk of atrial fibrillation (AF). However,
      definite conclusion has not yet been fully established. We examined whether SAHS
      increases AF incidence in common population and summarized all existing studies
      in a meta-analysis. We summarized the current studies by searching related
      database for potential papers of the association between SAHS and the risk of AF.
      Studies that reported original data or relative risks (RRs) with 95% confidence
      intervals (CIs) for the associations were included. Sensitivity analyses were
      performed by omitting each study iteratively and publication bias was detected by
      Begg's tests. Eight eligible studies met the inclusion criteria. Fixed effects
      meta-analysis showed that SAHS increased AF risk in the common population (RR =
      1.70, 95% CI: 1.53-1.89, P = 0.002, I2 = 69.2%). There was a significant
      association between mild SAHS and the risk of AF (RR = 1.52, 95% CI: 1.28-1.79, P
      = 0.01, I2 = 78.4%), moderate SAHS (RR = 1.88, 95% CI: 1.55-2.27, P = 0.017, I2 =
      75.6%), and severe SAHS (RR = 2.16, 95% CI: 1.78-2.62, P < 0.001, I2 = 91.0%).
      The results suggest that sleep apnea hypopnea syndrome could increase the risk of
      AF, and the higher the severity of SAHS, the higher risk of atrial fibrillation.

PMID- 29581976
TI  - Hypoxia Enhances Fusion of Oral Squamous Carcinoma Cells and Epithelial Cells
      Partly via the Epithelial-Mesenchymal Transition of Epithelial Cells.
AB  - Increasing evidence and indications showed that cell fusion is crucial in tumor
      development and metastasis, and hypoxia, a closely linked factor to tumor
      microenvironment, which can lead to EMT, induces angiogenesis and metastasis in
      tumor growth. However, the relationship between hypoxia and fusion has not been
      reported yet. EMT will change some proteins in the epithelial cell surface and
      the changes of proteins in cell surface may increase cell fusion. This study
      found that hypoxia promotes the spontaneous cell fusion between Oral Squamous
      Carcinoma Cells (OSCCs) and Human Immortalized Oral Epithelial Cells (HIOECs). At
      the same time, Hypoxia can lead to EMT, and hypoxia-pretreated HIOECs increased
      fusion rate with OSCC, while the fusion rate was significantly reduced by DAPT, a
      kind of EMT blocker. Therefore, epithelial cells can increase spontaneously cell
      fusion with OSCC by EMT. Our study may provide a new insight to link among tumor
      microenvironment, cell fusion, and cancer.

PMID- 29581978
TI  - Suprapedicular Circumferential Opening Technique of Percutaneous Endoscopic
      Transforaminal Lumbar Discectomy for High Grade Inferiorly Migrated Lumbar Disc
      Herniation.
AB  - Purpose: To evaluate the efficacy of suprapedicular circumferential opening
      technique (SCOT) of percutaneous endoscopic transforaminal lumbar discectomy
      (PETLD) for high grade inferiorly migrated lumbar disc herniation. Material and
      Methods: Eighteen consecutive patients who presented with back and leg pain with
      a single-level high grade inferiorly migrated lumbar disc herniation were
      included. High grade inferiorly migrated disc was removed by the SCOT through
      PETLD approach. Outcome evaluation was done with visual analog scale (VAS) and
      Mac Nab's criteria. Result: There were 14 males and 4 females. The mean age of
      patients was 53.3 +/- 14.12 years. One, 4, and 13 patients had disc herniation at
      L1-2, L3-4, and L4-5 levels, respectively, on MRI, which correlated with clinical
      findings. The mean follow-up duration was 8.4 +/- 4.31 months. According to Mac
      Nab's criteria, 9 patients (50%) reported excellent and the remaining 9 patients
      (50%) reported good outcomes. The mean preoperative and postoperative VAS for leg
      pain were 7.36 +/- 0.73 and 1.45 +/- 0.60, respectively (p < 0.001). Improvement
      in outcomes was maintained even at final follow-up. There was no complication.
      Conclusion: In this preliminary study we achieved good to excellent clinical
      results using the SCOT of PETLD for high grade inferiorly migrated lumbar disc
      herniation.

PMID- 29581979
TI  - Current Strategies of Endocrine Therapy in Elderly Patients with Breast Cancer.
AB  - Currently, the growing population of the elderly is one of biggest problems in
      terms of increase in geriatric diseases. Lack of data from large prospective
      studies on geriatric breast cancer patients often makes it difficult for
      clinicians to make treatments decisions for them. Because both benefit and risk
      of treatment should be taken into account, treatment is usually determined
      considering life expectancy or comorbidities in elderly patients. Treatment of
      breast cancer is differentiated according to histologic classifications, and
      hormone therapy is even adopted for patients with metastatic breast cancer if
      tumor tissue expresses hormone receptors. Endocrine therapy can offer great
      benefit to elderly patients considering its equivalent efficacy to chemotherapy
      with fewer toxicities if it is appropriately used. Aromatase inhibitors are
      usually prescribed agents in hormone therapy for elderly breast cancer patients
      due to their physiology after menopause. Here, endocrine therapy for elderly
      patients with breast cancer in neoadjuvant, adjuvant, and palliative setting is
      reviewed along with predictive adverse events resulting from the use of hormone
      agents.

PMID- 29581980
TI  - Mineral and Phytochemical Profiles and Antioxidant Activity of Herbal Material
      from Two Temperate Astragalus Species.
AB  - Only a few species of the large Astragalus genus, widely used for medicinal
      purposes, have been thoroughly studied for phytochemical composition. The aim of
      our research was to investigate the rarely studied species A. glycyphyllos L. and
      A. cicer L. for the distribution of mineral elements and phytochemicals in whole
      plants at two growth stages and in morphological fractions. We also investigated
      the capacity of the plant extracts to scavenge 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radicals and to chelate ferrous ions. Chemical composition and antioxidant
      properties depended on species, maturity, and plant part. Herbal material of A.
      glycyphyllos was richer in Fe, total phenolics, and flavonoids, whereas extracts
      of A. cicer showed a higher antioxidant activity. Young plants had more
      isoflavones, showed greater quenching of DPPH radicals, and exhibited better
      mineral profiles than flowering plants. Among plant parts, leaves were the most
      valuable plant material according to most characteristics investigated.
      Isoflavone concentration in flowers was lower than in leaves and stems. None of
      the Astragalus samples contained detectable amounts of the alkaloid swainsonine.
      The study demonstrates the potential of plant material from two Astragalus
      species as a valuable source of iron, phenolic substances including isoflavones,
      free-radical scavengers, and Fe2+ chelators for pharmaceutical use.

PMID- 29581981
TI  - Mechanism of Activating the Proprioceptive NT-3/TrkC Signalling Pathway by
      Reverse Intervention for the Anterior Cruciate Ligament-Hamstring Reflex Arc with
      Electroacupuncture.
AB  - The anterior cruciate ligament (ACL) is an important structure maintaining
      stability of the knee joints. Deficits in physical stability and the
      proprioceptive capabilities of the knee joints are observed, when the ACL is
      damaged. Additionally, a unilateral ACL injury can affect bilateral knee
      proprioception; therefore, proprioception of the ACL may play a key role in
      stability. Electroacupuncture therapy has a definite effect nerve regeneration.
      In this study, cynomolgus monkeys were randomly divided into 4 groups: the model
      control group, intervention of the injured knee with electroacupuncture (IIKE)
      group, intervention of the bilateral knees with electroacupuncture (IBKE) group,
      and the blank control group. The unilateral ACL injury model was developed in
      IIKE and IBKE groups; acupuncture points around the knees underwent intervention
      similarly in the IIKE and IBKE groups. Then, mRNA and protein expressions of NT-3
      and TrkC in the dorsal root ganglion and of growth-associated protein-43 in the
      ACL increased according to reverse-transcription quantitative polymerase chain
      reaction and Western blotting results. Decreased incubations and increased
      amplitudes were found for somatosensory-evoked potentials and motor nerve
      conduction velocity. The finding indicates that electroacupuncture may play an
      important role in the recovery of proprioception in the ACL by activating the NT
      3/TrkC signalling pathway.

PMID- 29581982
TI  - TGF-alpha Overexpression in Breast Cancer Bone Metastasis and Primary Lesions and
      TGF-alpha Enhancement of Expression of Procancer Metastasis Cytokines in Bone
      Marrow Mesenchymal Stem Cells.
AB  - Bone metastasis (BM) is the advanced complication of breast cancer, while bone
      marrow-derived mesenchymal stem cells (BMSCs) in the microenvironment unclearly
      contribute to cancer metastasis. This study investigated potential roles of
      transforming growth factor- (TGF-) alpha in the interaction between breast cancer
      and BMSCs in BM. Clinical cases of breast cancer with bone metastasis (BMBC),
      breast cancer without bone metastasis (Non-BM-BC), and benign fibroadenoma
      (Benign) were enlisted in a retrospective study. TGF-alpha was found obviously
      overexpressed in BM lesion of BMBC compared to primary lesion of both BMBC and
      Non-BM-BC (P < 0.01), and TGF-alpha was higher in primary lesion of both BMBC and
      Non-BM-BC (P < 0.01) than Benign group. Interestingly, TGF-alpha in nontumor
      tissues of both BMBC and Non-BM-BC was at a higher level than Benign group (P <
      0.01), and numbers of macrophages in nontumor tissues of both BMBC and Non-BM-BC
      (P < 0.01) were higher than Benign group. Furthermore, in cultured human BMSCs,
      TGF-alpha stimulated production of procancer cytokines including IL-6, VEGF,
      FGF10, FGF17, and TGF-beta1 in a dose-dependent manner. Thus, TGF-alpha in BC
      could potentially be an important signal of carcinogenesis and metastasis.
      Macrophages in the nontumor tissue of BC may not be protective but could promote
      cancer metastasis.

PMID- 29581983
TI  - Clinical Characteristics and Survival Outcomes for Non-Small-Cell Lung Cancer
      Patients with Epidermal Growth Factor Receptor Double Mutations.
AB  - Multiple randomized clinical trials have demonstrated that epidermal growth
      factor receptor (EGFR) exon 19 deletion (19Del) and exon 21 L858R mutation
      (L858R) are highly correlated with sensitivity to epidermal growth factor
      receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in non-small-cell lung
      cancer (NSCLC). A mutation in exon 20 (T790M) is reportedly associated with
      resistance to EGFR-TKIs. However, few studies have focused on patients harboring
      double mutations in these 3 mutation sites. In this retrospective study, forty
      five patients (45/2546, 1.7%) harbored double mutations of 19Del, L858R, and
      T790M. Twenty-four patients with EGFR double mutations received EGFR-TKI therapy.
      Clinical characteristics of these patients, including the response to EGFR-TKIs
      and progression-free survival outcome for EGFR-TKI treatment (PFS-TKI), were
      analyzed. Patients with EGFR double mutations were more likely to be nonsmokers,
      have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1,
      have adenocarcinoma, and be at stage III-IV. The ORR, DCR, and median PFS-TKI in
      patients harboring EGFR double mutations were lower than in patients with a
      single EGFR-activating mutation. The differences in ORR and DCR were
      statistically insignificant between the 3 groups. Patients with double mutations
      of 19Del and T790M had longer PFS-TKIs than patients in the other 2 groups.

PMID- 29581984
TI  - Dynamic Changes in Plasma MicroRNAs Have Potential Predictive Values in
      Monitoring Recurrence and Metastasis of Nasopharyngeal Carcinoma.
AB  - Although circulating microRNAs (miRNAs) have already proven to be useful as
      diagnostic and prognostic biomarkers in nasopharyngeal carcinoma (NPC), the
      potential of these molecules to monitor patients over time has been less
      explored. This study aimed to analyze dynamic changes in plasma miRNAs before and
      after treatment and explore their clinical significance in monitoring recurrence
      and metastasis of NPC. Candidate miRNAs were screened by microarray analysis and
      validated by real-time quantitative polymerase chain reaction (RT-qPCR). In the
      follow-up cohort including 102 patients, blood samples (plasma) were collected
      before the treatment initiation, 3 months, 6 months, and 12 months after
      treatments, and at the time of any recurrence or metastasis. Among these plasma
      miRNAs, miR-9-3p, miR-124-3p, miR-892b, and miR-3676-3p were significantly
      upregulated (P = 0.018, P = 0.039, P = 0.001, and P = 0.01, resp.) after
      treatment compared with pretreatment, and the four plasma miRNAs were
      downregulated again at recurrence or metastasis (P < 0.001, P = 0.015, P = 0.003,
      and P = 0.026, resp.). The dynamic changes in plasma miRNAs after treatment
      reflect the outcome of the disease and have the potential to monitor recurrence
      and metastasis in patients with NPC.

PMID- 29581985
TI  - The Feasibility of 3D Printing Technology on the Treatment of Pilon Fracture and
      Its Effect on Doctor-Patient Communication.
AB  - Purpose: The aim of this study was to assess the feasibility and effectiveness of
      the three-dimensional (3D) printing technology in the treatment of Pilon
      fractures. Methods: 100 patients with Pilon fractures from March 2013 to December
      2016 were enrolled in our study. They were divided randomly into 3D printing
      group (n = 50) and conventional group (n = 50). The 3D models were used to
      simulate the surgery and carry out the surgery according to plan in 3D printing
      group. Operation time, blood loss, fluoroscopy times, fracture union time, and
      fracture reduction as well as functional outcomes including VAS and AOFAS score
      and complications were recorded. To examine the feasibility of this approach, we
      invited surgeons and patients to complete questionnaires. Results: 3D printing
      group showed significantly shorter operation time, less blood loss volume and
      fluoroscopy times, higher rate of anatomic reduction and rate of excellent and
      good outcome than conventional group (P < 0.001, P < 0.001, P < 0.001, P = 0.040,
      and P = 0.029, resp.). However, no significant difference was observed in
      complications between the two groups (P = 0.510). Furthermore, the questionnaire
      suggested that both surgeons and patients got high scores of overall satisfaction
      with the use of 3D printing models. Conclusion: Our study indicated that the use
      of 3D printing technology to treat Pilon fractures in clinical practice is
      feasible.

PMID- 29581986
TI  - Negative Mood States Correlate with Laterobasal Amygdala in Collegiate Football
      Players.
AB  - A number of studies have suggested that sports-related concussion (SRC) may place
      individuals at increased risk for depression and negative outcomes including
      suicide. However, the mechanisms underlying a potential relationship between
      brain integrity and mood remain unclear. The current study is aimed at examining
      the association between amygdala shape, mood state, and postconcussion symptoms
      in collegiate football players. Thirty members of 1 football team completed the
      Profile of Mood States (POMS), the postconcussion symptom scale (PCSS), and an
      MRI protocol during preseason camp. T1-weighted images were acquired and three
      dimensional amygdala and probabilistic maps were created for shape analysis.
      Correlation analyses between POMS and PCSS and the relationship between POMS and
      amygdala shape were completed. In the amygdala, the left laterobasal subregion
      showed a positive relationship with the POMS total score and subscales scores. No
      significant relationship between PCSS and amygdala shape was found. Significant
      positive correlations were found between POMS subscales and PCSS. These results
      indicate that amygdala structure may be more closely associated with negative
      mood states than postconcussion symptoms. These findings suggest that premorbid
      individual differences in effect may provide critical insight into the
      relationship between negative mood and outcomes in collegiate football players
      with SRC.

PMID- 29581988
TI  - Ti-24Nb-4Zr-8Sn Alloy Pedicle Screw Improves Internal Vertebral Fixation by
      Reducing Stress-Shielding Effects in a Porcine Model.
AB  - To ensure the biomechanical properties of Ti-24Nb-4Zr-8Sn, stress-shielding
      effects were compared between Ti-24Nb-4Zr-8Sn and Ti-6Al-4V fixation by using a
      porcine model. Twelve thoracolumbar spines (T12-L5) of 12-month-old male pigs
      were randomly divided into two groups: Ti-24Nb-4Zr-8Sn (EG, n = 6) and Ti-6Al-4V
      (RG, n = 6) fixation. Pedicle screw was fixed at the outer edge of L4-5 vertebral
      holes. Fourteen measuring points were selected on the front of transverse process
      and middle and posterior of L4-5 vertebra. Electronic universal testing machine
      was used to measure the strain resistance of measuring points after forward and
      backward flexion loading of 150 N. Meanwhile, stress resistance was compared
      between both groups. The strain and stress resistance of measurement points 1, 2,
      5, 6, 9, and 10-14 in Ti-24Nb-4Zr-8Sn fixation was lower than that of Ti-6Al-4V
      fixation after forward and backward flexion loading (P < 0.05). The strain and
      stress resistance of measurement points 3, 4, 7, and 8 was higher in Ti-24Nb-4Zr
      8Sn fixation than that of Ti-6Al-4V fixation (P < 0.05). Stress-shielding effects
      of Ti-24Nb-4Zr-8Sn internal fixation were less than that of Ti-6Al-4V internal
      fixation. These results suggest that Ti-24Nb-4Zr-8Sn elastic fixation has more
      biomechanical goals than conventional Ti-6Al-4V internal fixation by reducing
      stress-shielding effects.

PMID- 29581989
TI  - Evidence for Seroprevalence in Human Localized Cutaneous Leishmaniasis Caused by
      Leishmania donovani in Sri Lanka.
AB  - Visceral leishmaniasis (VL) is considered as a major health threat in the Indian
      subcontinent. Leishmania donovani, a usually visceralizing species, causes
      cutaneous leishmaniasis (CL) in Sri Lanka. However, visceralizing potential of
      the local L. donovani is not yet fully understood. This project studied the
      seroprevalence of local CL by using an in-house ELISA. An IgG-based ELISA using
      crude Leishmania antigen (Ag) was developed and validated. A total of 50
      laboratory confirmed cases of locally acquired CL were examined using the newly
      developed ELISA. According to the optimized ELISA, seroprevalence of anti
      Leishmania IgG antibodies in the study group was 34.0% (n = 17/50). Majority of
      seropositive individuals were males (n = 13/17), representing 76%. Nearly half of
      the seropositive individuals were young adults (20-40 years, n = 9/17, 53%).
      Higher proportions of single lesions, large lesions, and nodular lesions were
      associated with a seroconversion. A proportion of local L. donovani infections
      leading to CL have the ability to raise an antibody response in the host. This
      may indicate early systemic involvement as one possibility. Study of a large
      number of patients with adequate follow-up would be useful.

PMID- 29581990
TI  - Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees
      (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens).
AB  - We have analyzed anatomic variations in the pectoralis major and pectoralis minor
      muscles of common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) and
      compared them to anatomic variations in these muscles in humans (Homo sapiens).
      We have macroscopically dissected these muscles in six adult Pan troglodytes,
      five Pan paniscus of ages ranging from fetus to adult, and five adult Homo
      sapiens. Although Pan troglodytes are thought to lack a separate pectoralis
      abdominis muscle, we have identified this muscle in three of the Pan troglodytes;
      none of the Pan paniscus, however, had this muscle. We have also found deep
      supernumerary fascicles in the pectoralis major of two Pan troglodytes and all
      five Pan paniscus. In all six Pan troglodytes, the pectoralis minor was inserted
      at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens, it was
      inserted at the coracoid process of the scapula. Some of the anatomic features
      and variations of these muscles in common chimpanzees and bonobos are similar to
      those found in humans, therefore enhancing our knowledge of primate comparative
      anatomy and evolution and also shedding light on several clinical issues.

PMID- 29581987
TI  - Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and
      Regeneration.
AB  - Meniscus injuries are very common and still pose a challenge for the orthopedic
      surgeon. Meniscus injuries in the inner two-thirds of the meniscus remain
      incurable. Tissue-engineered meniscus strategies seem to offer a new approach for
      treating meniscus injuries with a combination of seed cells, scaffolds, and
      biochemical or biomechanical stimulation. Cell- or scaffold-based strategies play
      a pivotal role in meniscus regeneration. Similarly, biochemical and biomechanical
      stimulation are also important. Seed cells and scaffolds can be used to construct
      a tissue-engineered tissue; however, stimulation to enhance tissue maturation and
      remodeling is still needed. Such stimulation can be biomechanical or biochemical,
      but this review focuses only on biochemical stimulation. Growth factors (GFs) are
      one of the most important forms of biochemical stimulation. Frequently used GFs
      always play a critical role in normal limb development and growth. Further
      understanding of the functional mechanism of GFs will help scientists to design
      the best therapy strategies. In this review, we summarize some of the most
      important GFs in tissue-engineered menisci, as well as other types of biological
      stimulation.

PMID- 29581991
TI  - Lifetime Traumatic Experiences and Disordered Eating among University Students:
      The Role of Posttraumatic Stress Symptoms.
AB  - The associations between lifetime traumatic events (TEs), posttraumatic stress
      (PTS) symptoms, and disordered eating (DE) were studied in a sample of 614
      university students (mean age 20 years). An anonymous questionnaire included 32
      lifetime TEs, IES-revised measured PTS symptoms, and EAT-26 evaluated DE
      symptoms. Statistical analyses included Pearson correlations and structural
      equation models (SEM) with bootstrapping method. Findings reveal the prevalence
      of DE in 8.1% of participants, while 73.9% of students experienced at least one
      lifetime TE. 52.0% of students with DE had PTS symptoms (p < 0.0001) and 30.8% of
      students with lifetime TEs had PTS symptoms (p < 0.001). In SEM, direct paths
      from lifetime TEs to PTS symptoms (0.38, p < 0.0001) and from PTS symptoms to DE
      (0.40, p < 0.0001) were observed. The final SEM confirmed the mediating role of
      PTS symptoms in the path between some TEs (traffic accident and seriously
      injured) and DE among the university students. If PTS symptoms are associated
      with DE, then addressing PTS symptoms in the context of DE treatment may improve
      treatment efficacy.

PMID- 29581992
TI  - Contrast-Enhanced Ultrasound Improves the Pathological Outcomes of US-Guided Core
      Needle Biopsy That Targets the Viable Area of Anterior Mediastinal Masses.
AB  - Based on the option that ultrasound-guided core needle biopsy (US-CNB) of the
      enhanced portion of anterior mediastinal masses (AMMs) identified by contrast
      enhanced ultrasound (CEUS) would harvest viable tissue and benefit the
      histological diagnoses, a retrospective study was performed to elucidate the
      correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found
      that CEUS potentially improved the diagnostic yield of AMMs compared with
      conventional US with a significant increase in the cellularity of samples.
      Furthermore, the marginal blood flow signals and absence of necrosis can predict
      the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of
      AMMs, as verified by CEUS, was able to harvest sufficient tissue with more
      cellularity that could be used for ancillary studies and improve the diagnostic
      yield. And CEUS was recommended to those patients with AMMs undergoing repeated
      US-CNB, with the absence of marginal blood signals or presence of necrosis.

PMID- 29581993
TI  - Hypereosinophilic Syndrome Complicated by Eosinophilic Myocarditis With Dramatic
      Response to Steroid.
AB  - Introduction. Eosinophilic myocarditis is an infiltrative disease that affects
      the myocardium leading to various presentations. It can be precipitated by
      medications, helminthiasis, or hypereosinophilic syndrome. Case. We present the
      case of a young, male patient who presented with palpitations and dyspnea and was
      found to have heart failure with reduced ejection fracture of 12%. His past
      medical history was significant for recent lung problem treated with steroids.
      Based on his history and laboratory findings, he was started on intravenous
      steroids for treatment of eosinophilic myocarditis. Within 3 days, his ejection
      fracture improved to 35%. Conclusion. Given the nonspecific clinical
      presentations, mimicking other diseases, high index of suspicion is warranted to
      diagnose eosinophilic myocarditis. This is crucial as early detection and
      treatment with steroids can lead to a dramatic response.

PMID- 29581994
TI  - Does the Reliability of Reporting in Injury Surveillance Studies Depend on Injury
      Definition?
AB  - Background: Choosing an appropriate definition for injury in injury surveillance
      studies is essential to ensure a balance among reporting reliability, providing
      an accurate representation of injury risk, and describing the nature of the
      clinical demand. Purpose: To provide guidance on the choice of injury definition
      for injury surveillance studies by comparing within- and between-team variability
      in injury incidence with >24-hour and >7-day time-loss injury definitions in a
      large multiteam injury surveillance study. Study Design: Cohort study
      (diagnosis); Level of evidence, 2. Methods: Injury data were reported for 2248
      professional rugby union players from 15 Premiership Rugby clubs over 12 seasons.
      Within-team percentage coefficient of variation and mean between-team standard
      deviation (expressed as a percentage coefficient of variation) in injury
      incidence rates (injuries per 1000 player match hours) were calculated. For both
      variables, a comparison was made between >24-hour and >7-day injury incidence
      rates in terms of the magnitude of the observed effects. Results: The overall
      mean incidence across the population with a >24-hour time-loss injury definition
      was approximately double the reported incidence with the >7-day definition. There
      was a 10% higher between-team variation in match injury incidence rates with the
      >24-hour time-loss definition versus the >7-day definition. Conclusion: There was
      a likely higher degree of between-team variation in match injury incidence rates
      with a >24-hour time-loss definition than with a >7-day definition of injury.
      However, in professional sports settings, it is likely that the benefits of using
      a more inclusive definition of injury (improved understanding of clinical demand
      and the appropriate and accurate reporting of injury risk) outweigh the small
      increase in variation in reporting consistency.

PMID- 29581995
TI  - Role of Rotational Kinematics in Minimizing Elbow Varus Torques for Professional
      Versus High School Pitchers.
AB  - Background: Elbow injury rates among baseball pitchers are rapidly rising.
      However, this increase has been most dramatic among high school (HS) pitchers.
      Purpose: To examine pitch velocity and the kinetic and kinematic characteristics
      of HS versus professional (PRO) pitchers to identify potential differences that
      may play a role in the increased risk of ulnar collateral ligament injury in
      youth pitchers. Study Design: Controlled laboratory study. Methods: A total of 37
      HS (mean +/- SD: age, 16 +/- 1 years) and 40 PRO (age, 21 +/- 2 years) baseball
      pitchers completed maximal-effort baseball pitches during a single testing
      session, from which pitch velocity (PV), absolute and normalized elbow varus
      torque (EVTA and EVTN, respectively) during arm cocking and at maximum shoulder
      external rotation (MER), and 8 other elbow and shoulder torques or forces and
      rotational kinematics of the pelvis and trunk were analyzed, recorded, and
      compared. Results: PV was greater in PRO than HS athletes; EVTA was greater in
      PRO than HS athletes during arm cocking and at MER; but EVTN was similar during
      arm cocking and greater in HS than PRO athletes at MER. In PRO athletes, PV was
      not related to EVTA during arm cocking or MER (r = 0.01-0.05). Furthermore, in
      PRO athletes, EVTA during arm cocking and at MER were inversely related to upper
      trunk rotation at hand separation and foot contact and to pelvis rotation at
      elbow extension (r = -0.30 to -0.33). In contrast, in HS athletes, PV was
      strongly related to EVTA during arm cocking and MER (r = 0.76-0.77). Furthermore,
      in HS athletes, PV and EVTA during arm cocking and at MER were moderately or
      strongly related to the other elbow and shoulder torques and forces (r = 0.424
      0.991), and EVTA was not related to upper trunk rotation or pelvis rotation
      throughout the throwing motion (r = -0.16 to 0.15). Conclusion: The kinetic and
      rotational kinematic differences observed between PRO and HS pitchers in this
      study may help explain the greater performance of PRO pitchers while allowing
      them to minimize EVT during pitching. HS pitchers, however, do not appear to be
      as capable of utilizing the forces generated by rotation of their trunk and
      pelvis to aid in pitching, and those who throw the hardest generate the greatest
      forces at the shoulder and elbow. As a result, they experience higher EVTs
      relative to their body size, which may place them at an increased risk of injury.
      Clinical Relevance: HS pitchers throw harder primarily by generating larger
      forces in the arm and shoulder. Thus, owing to the relative physical immaturity
      of HS versus PRO pitchers, these factors may place them at an increased risk of
      injury. Coaches may first wish to focus on improving the rotational kinematics of
      HS pitchers rather than first focusing on achieving greater pitch velocities.

PMID- 29581996
TI  - A 5-Strand Hamstring Autograft Achieves Outcomes Comparable to Those of a 4
      Strand Hamstring Autograft With a Graft Diameter of 8 mm or More in Anterior
      Cruciate Ligament Reconstruction.
AB  - Background: Quadrupled (4-strand) hamstring tendon autografts are commonly used
      in anterior cruciate ligament (ACL) reconstruction, but there is significant
      variability in their diameter. The 5-strand hamstring autograft has been used as
      a means of increasing the graft diameter in patients with undersized hamstring
      grafts. Purpose: To report the outcomes of primary ACL reconstruction using 5
      strand hamstring autografts in patients in whom the 4-strand configuration
      produced a graft diameter of <8 mm and to compare these outcomes with those of
      ACL reconstruction using 4-strand semitendinosus-gracilis autografts with a graft
      diameter of >=8 mm. Study Design: Cohort study; Level of evidence, 2. Methods:
      The primary study group comprised 25 patients who underwent ACL reconstruction
      using a 5-strand hamstring autograft. The comparison group comprised 20 patients
      who underwent ACL reconstruction using a 4-strand hamstring autograft with a
      graft diameter of >=8 mm. Interference screw fixation was used at the tibial and
      femoral ends for both groups of patients. Subjective questionnaires, including
      the Knee injury and Osteoarthritis Outcome Score (KOOS), the Lysholm score, and
      the Physical Component Summary and Mental Component Summary of the Short Form-36
      (SF-36), were administered preoperatively as well as at 1- and 2-year follow-up
      visits. Results: There were no significant differences in the patient
      demographics and preoperative scores between the 2 groups. The mean graft
      diameter was 9.06 +/- 0.60 mm in the 5-strand group and 8.13 +/- 0.32 mm in the 4
      strand group (P < .05). There was no statistically significant difference between
      groups on postoperative Lysholm, KOOS Pain, KOOS Symptoms, KOOS Activities of
      Daily Living, KOOS Sports, KOOS Quality of Life, and SF-36 Physical Component
      Summary scores. Conclusion: In primary ACL reconstruction, the 5-strand hamstring
      autograft achieves clinical outcomes that are comparable to those of the 4-strand
      hamstring autograft with a graft diameter of >=8 mm. The 5-strand graft technique
      is therefore a useful means of increasing the graft diameter when faced with an
      undersized hamstring graft.

PMID- 29581997
TI  - Cardiac Arrest in a Vitamin D-Deficient Infant.

PMID- 29581999
TI  - Astrocyte dysfunction following molybdenum-associated purine loading could
      initiate Parkinson's disease with dementia.
AB  - Sporadic or idiopathic Parkinson's disease is a movement disorder with a
      worldwide distribution, a long pre-clinical latent period and a frequent
      association with dementia. The combination of molybdenum deficiency and purine
      ingestion could explain the movement disorder, the distribution, the latent
      period and the dementia association. Recent studies in sheep have shown that
      molybdenum deficiency enables some dietary purines to accumulate in the central
      nervous system. This causes astrocyte dysfunction, altered neuromodulation and
      eventually irreversible central nervous system disease. Humans and sheep share
      the ability to salvage purines and this ability places humans at risk when they
      ingest xanthosine, inosine, adenosine and guanosine. Adenosine ingestion in
      molybdenum-deficient humans will lead to adenosine loading and potentially a
      disturbance to the A2a adenosine receptors in the nigro-striatum. This could
      result in Parkinson's disease. Guanosine ingestion in molybdenum-deficient humans
      will lead to guanosine loading and potentially a disturbance to the guanosine
      receptors in the hippocampus, amygdala and ventral striatum. This could result in
      dementia. The molybdenum content of the average daily diet in the United States
      is 0.07 ppm and in the United Kingdom 0.04 ppm. Central nervous system disease
      occurs in sheep at <0.04 ppm. Consistent with the role proposed for molybdenum
      deficiency in Parkinson's disease is the observation that affected individuals
      have elevated sulfur amino acid levels, depressed sulfate levels, and depressed
      uric acid levels. Likewise the geographical distribution of Parkinson's dementia
      complex on Guam corresponds with the distribution of molybdenum-deficient soils
      hence molybdenum-deficient food gardens on that island.

PMID- 29581998
TI  - Long-term effect of critical illness after severe paediatric burn injury on
      cardiac function in adolescent survivors: an observational study.
AB  - Background: Sepsis, trauma, and burn injury acutely depress systolic and
      diastolic cardiac function; data on long-term cardiac sequelae of pediatric
      critical illness are sparse. This study evaluated long-term systolic and
      diastolic function, myocardial fibrosis, and exercise tolerance in survivors of
      severe pediatric burn injury. Methods: Subjects at least 5 years after severe
      burn (post-burn:PB) and age-matched healthy controls (HC) underwent
      echocardiography to quantify systolic function (ejection fraction[EF%]),
      diastolic function (E/e'), and myocardial fibrosis (calibrated integrated
      backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen
      consumption (VO2) and heart rate at rest and peak exercise. Demographic
      information, clinical data, and biomarker expression were used to predict long
      term cardiac dysfunction and fibrosis. Findings: Sixty-five subjects
      (PB:40;HC:25) were evaluated. At study date, PB subjects were 19+/-5 years, were
      at 12+/-4 years postburn, and had burns over 59+/-19% of total body surface area,
      sustained at 8+/-5 years of age. The PB group had lower EF% (PB:52+/-9%;HC:61+/
      6%; p=0.004), E/e' (PB:9.8+/-2.9;HC: 5.4+/-0.9;p<0.0001), VO2peak (PB:37.9+/
      12;HC: 46+/-8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161+/-26;HC:182+/
      13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic
      dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial
      fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis,
      systolic dysfunction, and diastolic dysfunction. Interpretation: Severe pediatric
      burn injury may have lasting impact on cardiac function into young adulthood and
      is associated with myocardial fibrosis and reduced exercise tolerance. Given the
      strong predictive value of systolic and diastolic dysfunction, these patients
      might be at increased risk for early heart failure, associated morbidity, and
      mortality. Funding: Conflicts of Interest and Sources of Funding: The authors do
      not have any conflicts of interest to declare. This work was supported by NIH
      (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32
      GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children
      (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG
      CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It
      was also made possible with the support of UTMB's Institute for Translational
      Sciences, supported in part by a Clinical and Translational Science Award
      (UL1TR000071) from the National Center for Advancing Translational Sciences
      (NIH).

PMID- 29582001
TI  - A "Pathology Explanation Clinic (PEC)" for Patient-Centered Laboratory Medicine
      Test Results.
AB  - This concept paper addresses communication issues arising between physicians and
      their patients. To facilitate the communication of essential diagnostic pathology
      information to patients, and address their questions and concerns, we propose
      that "Pathology Explanation Clinics" be created. The Pathology Explanation
      Clinics would provide a channel for direct communications between pathologists
      and patients. Pathologists would receive special training as "Certified
      Pathologist Navigators" in preparation for this role. The goal of Pathology
      Explanation Clinics would be to help fill gaps in communication of information
      contained in laboratory reports to patients, further explain its relevance, and
      improve patient understanding of the meaning of such information and its impact
      on their health and health-care choices. Effort would be made to ensure that
      Certified Pathologist Navigators work within the overall coordination of care by
      the health-care team.

PMID- 29582002
TI  - The Continuing Fellowship Conundrum.

PMID- 29582003
TI  - Editor's letter.

PMID- 29582000
TI  - Rhythmic abilities and musical training in Parkinson's disease: do they help?
AB  - Rhythmic auditory cues can immediately improve gait in Parkinson's disease.
      However, this effect varies considerably across patients. The factors associated
      with this individual variability are not known to date. Patients' rhythmic
      abilities and musicality (e.g., perceptual and singing abilities, emotional
      response to music, and musical training) may foster a positive response to
      rhythmic cues. To examine this hypothesis, we measured gait at baseline and with
      rhythmic cues in 39 non-demented patients with Parkinson's disease and 39 matched
      healthy controls. Cognition, rhythmic abilities and general musicality were
      assessed. A response to cueing was qualified as positive when the stimulation led
      to a clinically meaningful increase in gait speed. We observed that patients with
      positive response to cueing (n = 17) were more musically trained, aligned more
      often their steps to the rhythmic cues while walking, and showed better music
      perception as well as poorer cognitive flexibility than patients with non
      positive response (n = 22). Gait performance with rhythmic cues worsened in six
      patients. We concluded that rhythmic and musical skills, which can be modulated
      by musical training, may increase beneficial effects of rhythmic auditory cueing
      in Parkinson's disease. Screening patients in terms of musical/rhythmic abilities
      and musical training may allow teasing apart patients who are likely to benefit
      from cueing from those who may worsen their performance due to the stimulation.

PMID- 29582004
TI  - Now and at the Hour of Death.
AB  - With Alzheimer disease, the challenge of death can be unique to each who
      experience it: the caretaker, the family, the health-care professional, and the
      victim himself. Death of personality, of memory, and of physical skills wears
      away the fabric of relationships, leaving little hope of any return to normalcy.
      To some, this reflection exhibits how faith sustains hope and comforts those
      afflicted, despite the odds of inevitable loss. To others it reflects upon the
      poignant complexities associated with palliative care and the demand for
      individualized attention to the beliefs, norms, and values of each situation, no
      matter the culture, religion, age, or race. No two cases are ever the same in the
      face of death, yet for those who experience it, all must appreciate how
      difficult, unique, personal, and memorable such moments can be.

PMID- 29582005
TI  - Living With Multiple Myeloma: A Focus Group Study of Unmet Needs and Preferences
      for Survivorship Care.
AB  - Purpose: To describe the unmet informational, psychological, emotional, social,
      practical, and physical needs and preferences for posttreatment survivorship care
      of individuals living with multiple myeloma to inform the development of
      relevant, person-centered, survivorship services. Methods: An exploratory,
      descriptive study using 2 focus groups with 14 participants, 6 to 49 months
      postdiagnosis. Results: Thematic analysis revealed 7 key themes: information
      needs, experience with health-care professionals, coping with side effects,
      communicating with family and friends, dealing with emotions, support needs, and
      living with the chronicity of myeloma. Participants described key characteristics
      of survivorship care relevant to their needs and indicated they would like a more
      whole of person approach to follow-up when the main treatment phases had
      completed. Conclusion: Participants in this study described unmet needs across a
      breadth of domains that varied over time. The development of flexible, person
      centered approaches to comprehensive survivorship care is needed to address the
      considerable quality-of-life issues experienced by people living with multiple
      myeloma. Nurse-led care may offer 1 viable model to deliver enhanced patient
      experience-providing the vital "link" that people described as missing from their
      survivorship care.

PMID- 29582006
TI  - What's Mine is Yours: Long-Term Experiences of Good Samaritan Organ Donors.
AB  - This study is a long-term follow-up on the health and quality of life of Good
      Samaritan living organ donors who donated an average of 10 years ago. Thirteen
      donors (kidney, liver, and lung) completed 2 surveys. Data from the RAND 36-Item
      Health Survey showed that for all domains, as well as the physical and mental
      component summary scales, the Good Samaritan donor outcomes were superior to the
      general population (P < .0001). Data from the European Living Donor Satisfaction
      Survey (EULID) showed that in all 8 theme areas, the donors reported
      statistically significant positive reactions as compared to negative reactions.
      With regard to self-reported health status, there was a strong, positive
      correlation between the RAND 36-Item Health Survey and the EULID (n = 13, Pearson
      correlation coefficient: 0.874). All but 1 donor reported good, very good, or
      excellent health status. Although donors overwhelmingly reported positivity about
      the donation experience, narrative comments about adverse events and recipient
      death must keep transplant teams alert to these critical areas. Good Samaritan
      organ donors come to the hospital healthy, give a gift to a stranger, and
      sometimes leave and linger disabled. Donor teams should be observing,
      questioning, and responding in an effort to maximize their welfare. This research
      is unique because investigation of the long-term health and psychosocial outcomes
      of Good Samaritan organ donors is rare. Existing studies that report long-term
      outcomes of kidney donors do not separately analyze Good Samaritan donor data
      from related living donors.

PMID- 29582007
TI  - Carer Appraisal Scale: A Pilot Study of a Novel Carer-Based Assessment of Patient
      Functioning.
AB  - Measurement of patient outcomes is an integral part of mental health service
      evaluation, as well as guiding clinical practice to ensure best outcomes for
      patients. Moreover, carers have long held a need for a voice in care outcomes.
      Despite there existing numerous tools for quantifying patient functioning based
      on clinician assessments or self-reports, there is a serious paucity of tools
      available for the carers of patients to appraise their functioning. This tool,
      developed for use in a community aged care psychiatric service, involves 4
      sections-a global impression of patient progress, a scorable checklist of patient
      functioning in multiple domains, a qualitative section for identifying the most
      pressing concerns from the carer's perspective, and an open-ended feedback on
      treatment to date. In this pilot study, the Carer Appraisal Scale was found to
      have a fair correlation with the Health of Nation Outcomes Scale for over 65.
      This tool has potential for use in community aged care psychiatric services, as
      it provides a framework for communication of concerns, assists in prioritizing
      care, and adds value to clinician treatment plans, as well as providing another
      dimension to assessment of the patient while empowering carers in care
      participation. Practical implications of its use, limitations, and potential for
      modifications are also discussed.

PMID- 29582008
TI  - Patient-Centered Obstetric Care in the Age of Cell-Free Fetal DNA Prenatal
      Screening.
AB  - Purpose: The clinical introduction of innovative prenatal genetic technologies
      challenges patients and providers to find new ways of fostering informed decision
      making in a setting characterized by complexity and uncertainty. As prenatal
      genetic technology advances, important questions remain about how to structure
      patient-centered conversations that effectively prepare pregnant patients to make
      informed choices about the different genetic conditions for which this new form
      screening may be used. Methods: Focus groups were conducted with 23 pregnant
      women to identify informational needs and decision-making preferences regarding
      emerging and anticipated applications of cell-free fetal DNA screening, the
      newest form of prenatal genetic screening. Results: Participants were in favor of
      obtaining more genetic information about the fetus than provided by conventional
      screens but acknowledged the challenges inherent in navigating the unique
      complexities of the decision-making process. The provider-patient relationship
      was seen as an important resource to navigate the associated uncertainties at
      each stage of the screening process. Participants emphasized the need for
      initiatives to support a personalized, accurate, and unbiased discussion about
      prenatal genetic risk and assessment. Conclusion: Continued advances in prenatal
      genetic screening call for new approaches to structure patient-centered
      communication to facilitate increasingly complex decisions about fetal genetic
      risk and assessment.

PMID- 29582009
TI  - Developing and Translating a New Model for Teaching Empowerment Into Routine
      Chronic Care Management: An International Patient-Centered Project.
AB  - Background: Health professional education has been criticized for not integrating
      patient expertise into professional curricula to develop professional skills in
      patient empowerment. Objective: To develop and translate a new expert patient
      centered model for teaching empowerment into professional education about routine
      chronic care management. Methods: Eight Finnish patients (known as expert
      patients), 31 students, and 11 lecturers from 4 European countries participated
      in a new pilot intensive educational module. Thirteen focus groups, artefacts,
      and an online student evaluation were analyzed using a thematic analysis and
      triangulated using a meta-matrix. Results: A patient-centered pedagogical model
      is presented, which describes 3 phases of empowerment: (1) preliminary work, (2)
      the elements of empowerment, and (3) the expected outcomes. These 3 phases were
      bound by 2 cross-cutting themes "time" and "enabling resources." Conclusion:
      Patient expertise was embedded into the new module curriculum. Using an example
      of care planning, and Pentland and Feldman's theory of routine organization, the
      results are translated into a patient-centered educational model for teaching
      empowerment to health profession students.

PMID- 29582010
TI  - Dimensions of Phenomenology in Exploring Patient's Suffering in Long-Life
      Illnesses: Qualitative Evidence Synthesis.
AB  - Background: Patients' suffering has been increasingly investigated by health-care
      researchers especially in the chronically ill. Suffering is viewed as a
      progressive negative consequence that associated with pain, impaired self-esteem,
      and social alienation. This qualitative evidence synthesis aimed to provide
      further insights into the application of phenomenology in explaining suffering
      among patients with chronic illnesses. Methods: Studies included in this
      qualitative evidence synthesis study were retrieved by searching from the
      following electronic databases: CINAHL, PubMed Central, and EBSCO. Findings:
      Phenomenology is regarded as influential to generate in-depth evidence about
      suffering that are grounded in chronically ill patients' perspectives. The
      philosophical constructs of suffering suggested fundamental dimensions such as
      stress, distress, hopelessness, and depression along with pain. Evidence
      encompasses the entire manifestation of suffering in which all interrelated
      meanings are understood and referred to a unique structure. Hermeneutic
      phenomenology was adopted as an effective strategy to elucidate human experience
      leading to the discovery of the embedded meanings of life experience. Conclusion:
      The phenomenological approach provides nursing research with the pathway to
      explore patients' suffering experiences in the chronically ill.

PMID- 29582011
TI  - Mitigating Burden Associated With Informal Caregiving.
AB  - Informal caregiving is the most common form of long-term care provided in the
      United States, and with the projected rapid growth of older adults, informal
      caregiving will be even more critical in the foreseeable future. In the United
      States, slightly more than 20% of informal caregivers provide care for more than
      one care recipient, and 10% provide care for three or more care recipients.
      Caring for a dependent, older adult patient may have negative effects on
      physical, psychological, psychosocial, social and financial health of caregivers.
      Careful assessment of the impact of informal caregiving on the caregiver's
      functioning is imperative, and will enable a practitioner to not only find ways
      to help caregivers shoulder the effects of caregiving, but also to measure the
      effectiveness of interventions that seek to mitigate the effects of caregiving.

PMID- 29582012
TI  - Improving Patient Experiences and Outcomes Through Personal Care Aide Training.
AB  - Introduction: The rapidly aging US population is resulting in major challenges
      including delivering quality care at lower costs in the face of a critical health
      care workforce shortage. The movement toward home care has dramatically increased
      the need for qualified, paid personal care aides (PCAs). Adequate PCA training
      that focuses on skills for person-centered, at home support is an imperative.
      This study provides evidence that clients of PCAs who have completed a
      comprehensive, evidence-based PCA training program, titled Building
      Training...Building Quality (BTBQ), report higher satisfaction and better health
      outcomes, compared to clients of PCAs with lesser or other training. Methods: A
      mixed-methods, quasi-experimental design was used to compare self-reported survey
      responses from clients of BTBQ-trained PCAs (treatment group) with responses from
      clients of non-BTBQ-trained PCAs (control group). Results: Clients of BTBQ
      trained PCAs had significantly fewer falls and emergency department visits
      compared to clients whose PCAs had no BTBQ training (P < .05). Conclusion: BTBQ
      like PCA training reduces costly adverse events.

PMID- 29582013
TI  - Occasionally a Patient: Always a Person.

PMID- 29582015
TI  - Disparities in breast cancer tumor characteristics, treatment, time to treatment,
      and survival probability among African American and white women.
AB  - African American (AA) women have a 42% higher breast cancer death rate compared
      to white women despite recent advancements in management of the disease. We
      examined racial differences in clinical and tumor characteristics, treatment and
      survival in patients diagnosed with breast cancer between 2005 and 2014 at a
      single institution, the James Cancer Hospital, and who were included in the
      Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Cancer
      Registry in Columbus OH. Statistical analyses included likelihood ratio chi
      square tests for differences in proportions, as well as univariate and
      multivariate Cox proportional hazards regressions to examine associations between
      race and overall and progression-free survival probabilities. AA women made up
      10.2% (469 of 4593) the sample. Average time to onset of treatment after
      diagnosis was almost two times longer in AA women compared to white women (62.0
      days vs 35.5 days, p < 0.0001). AA women were more likely to report past or
      current tobacco use, experience delays in treatment, have triple negative and
      late stage breast cancer, and were less likely to receive surgery, especially
      mastectomy and reconstruction following mastectomy. After adjustment for
      confounding factors (age, grade, and surgery), overall survival probability was
      significantly associated with race (HR = 1.33; 95% CI 1.03-1.72). These findings
      highlight the need for efforts focused on screening and receipt of prompt
      treatment among AA women diagnosed with breast cancer.

PMID- 29582016
TI  - Oriented chiral water wires in artificial transmembrane channels.
AB  - Aquaporins (AQPs) feature highly selective water transport through cell
      membranes, where the dipolar orientation of structured water wires spanning the
      AQP pore is of considerable importance for the selective translocation of water
      over ions. We recently discovered that water permeability through artificial
      water channels formed by stacked imidazole I-quartet superstructures increases
      when the channel water molecules are highly organized. Correlating water
      structure with molecular transport is essential for understanding the underlying
      mechanisms of (fast) water translocation and channel selectivity. Chirality adds
      another factor enabling unique dipolar oriented water structures. We show that
      water molecules exhibit a dipolar oriented wire structure within chiral I-quartet
      water channels both in the solid state and embedded in supported lipid bilayer
      membranes (SLBs). X-ray single-crystal structures show that crystallographic
      water wires exhibit dipolar orientation, which is unique for chiral I-quartets.
      The integration of I-quartets into SLBs was monitored with a quartz crystal
      microbalance with dissipation, quantizing the amount of channel water molecules.
      Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the
      first experimental observation of dipolar oriented water structures within
      artificial water channels inserted in bilayer membranes. Confirmation of the
      ordered confined water is obtained via molecular simulations, which provide
      quantitative measures of hydrogen bond strength, connectivity, and the stability
      of their dipolar alignment in a membrane environment. Together, uncovering the
      interplay between the dipolar aligned water structure and water transport through
      the self-assembled I-quartets is critical to understanding the behavior of
      natural membrane channels and will accelerate the systematic discovery for
      developing artificial water channels for water desalting.

PMID- 29582017
TI  - Stabilizing electrochemical interfaces in viscoelastic liquid electrolytes.
AB  - Electrodeposition is a widely practiced method for creating metal, colloidal, and
      polymer coatings on conductive substrates. In the Newtonian liquid electrolytes
      typically used, the process is fundamentally unstable. The underlying
      instabilities have been linked to failure of microcircuits, dendrite formation on
      battery electrodes, and overlimiting conductance in ion-selective membranes. We
      report that viscoelastic electrolytes composed of semidilute solutions of very
      high-molecular weight neutral polymers suppress these instabilities by multiple
      mechanisms. The voltage window DeltaV in which a liquid electrolyte can operate
      free of electroconvective instabilities is shown to be markedly extended in
      viscoelastic electrolytes and is a power-law function, DeltaV : eta1/4, of
      electrolyte viscosity, eta. This power-law relation is replicated in the
      resistance to ion transport at liquid/solid interfaces. We discuss consequences
      of our observations and show that viscoelastic electrolytes enable stable
      electrodeposition of many metals, with the most profound effects observed for
      reactive metals, such as sodium and lithium. This finding is of contemporary
      interest for high-energy electrochemical energy storage.

PMID- 29582018
TI  - Critical advancements in achieving high power and stable nonprecious metal
      catalyst-based MEAs for real-world proton exchange membrane fuel cell
      applications.
AB  - Despite great progress in the development of nonprecious metal catalysts (NPMCs)
      over the past several decades, the performance and stability of these promising
      catalysts have not yet achieved commercial readiness for proton exchange membrane
      fuel cells (PEMFCs). Through rational design of the cathode catalyst layer (CCL),
      we demonstrate the highest reported performance for an NPMC-based membrane
      electrode assembly (MEA), achieving a peak power of 570 mW/cm2 under air. This
      record performance is achieved using a precommercial catalyst for which nearly
      all pores are <3 nm in diameter, challenging previous beliefs regarding the need
      for larger catalyst pores to achieve high current densities. This advance is
      achieved at industrially relevant scales (50 cm2 MEA) using a precommercial NPMC.
      In situ electrochemical analysis of the CCLs is also used to help gain insight
      into the degradation mechanism observed during galvanostatic testing. Overall,
      the performance of this NPMC-based MEA has achieved commercial readiness and will
      be introduced into an NPMC-based product for portable power applications.

PMID- 29582019
TI  - Truncating SLC5A7 mutations underlie a spectrum of dominant hereditary motor
      neuropathies.
AB  - Objective: To identify the genetic cause of disease in 2 previously unreported
      families with forms of distal hereditary motor neuropathies (dHMNs). Methods: The
      first family comprises individuals affected by dHMN type V, which lacks the
      cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII
      observed in the second family. Next-generation sequencing was performed on the
      proband of each family. Variants were annotated and filtered, initially focusing
      on genes associated with neuropathy. Candidate variants were further investigated
      and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough
      patient phenotyping was completed, comprising clinical history, examination, and
      neurologic investigation. Results: dHMNs are a heterogeneous group of peripheral
      motor neuron disorders characterized by length-dependent neuropathy and
      progressive distal limb muscle weakness and wasting. We previously reported a
      dominant-negative frameshift mutation located in the concluding exon of the
      SLC5A7 gene encoding the choline transporter (CHT), leading to protein
      truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended
      UK family. In this study, our genetic studies identified distinct heterozygous
      frameshift mutations located in the last coding exon of SLC5A7, predicted to
      result in the truncation of the CHT C-terminus, as the likely cause of the
      condition in each family. Conclusions: This study corroborates C-terminal CHT
      truncation as a cause of autosomal dominant dHMN, confirming upper limb
      predominating over lower limb involvement, and broadening the clinical spectrum
      arising from CHT malfunction.

PMID- 29582021
TI  - Enhancement of Y123 dye-sensitized solar cell performance using plasmonic gold
      nanorods.
AB  - The role of the surface plasmon resonance (SPR) of gold nanorods (Au NRs) on the
      performance of Y123 dye-sensitized solar cells (DSSC) was investigated. DSSCs
      were fabricated by incorporating different concentrations (0.6 to 3.0 wt%) of Au
      NRs into TiO2 photoanodes. With an increase in the concentration of the Au NRs,
      the light absorption by the Y123 dye loaded photoanodes enhanced linearly, but
      the charge extraction was susceptible to the concentration of the Au NRs. With
      optimized concentrations (~1.8 wt%) of the Au NRs, the photocurrent of the DSSC
      enhanced from 12.45 to 15.74 mA cm-2, and the power conversion efficiency (PCE)
      improved from 5.31 to 8.86%. The DSSC performance was also verified using Au
      nanoparticles (the PCE was enhanced from 5.31 to 7.72%) for comparison with the
      Au NR DSSC performance, which demonstrated the advantage of the Au NRs' shape
      effect with longitudinal SPR due to the modified light interaction. To explain
      the experimental observations of the plasmonic DSSC, the Au NRs' extinction
      efficiency and spatial distribution of the near-fields in complete and porous
      TiO2 media were also estimated using the finite-element method.

PMID- 29582020
TI  - The Effect of Preoperative Biliary and Pancreatic Drainage on Postoperative
      Pancreatic Fistula: A Retrospective Cohort Study.
AB  - Background  Surgeons and endoscopists welcome routine preoperative biliary
      drainage prior to pancreaticoduodenectomy despite evidence that it increases
      complications. Its effect on postoperative pancreatic fistula is variably
      reported in literature. Simultaneous biliary and pancreatic drainage is rarely
      performed for very selected indications and its effects on postoperative
      pancreatic fistula are largely unknown. Our aim was to analyze the same while
      eliminating confounding factors. Methods  Retrospective single center cohort
      study of patients who underwent pancreaticoduodenectomy over the past 10 years
      for carcinoma obstructing the lower common bile duct. Patients who underwent
      biliary stenting alone, biliary and pancreatic stenting, and no stenting prior to
      pancreaticoduodenectomy were the three study cohort groups and their records were
      scrutinized for the incidence of postoperative pancreatic fistula. Results  Sixty
      two patients underwent biliary stenting alone, 5 patients underwent both biliary
      and pancreatic stenting, and 237 patients were not stented in the adenocarcinoma
      group without chronic pancreatitis. The pancreatic fistula rate was similar in
      the patients who underwent biliary stenting alone when compared with the group
      which was not stented. (24/62 versus 67/237, odds ratio [OR] =0.619, confidence
      interval (CI) =0.345-1.112, p  = 0.121). However, the patients who underwent both
      biliary and pancreatic stenting had a significant increase in postoperative
      pancreatic fistula compared with the not stented ( p  = 0.003). By univariate and
      multivariate analysis using Firth logistic regression, pancreatic texture (OR =
      1.205, CI = 0.103-2.476, p  = 0.032) and the presence of a biliary and pancreatic
      stent (OR = 2.695, CI = 0.273-7.617, p  = 0.027) were the significant factors
      affecting pancreatic fistula. Conclusion  Preoperative biliary drainage alone has
      no significant influence on postoperative pancreatic fistula except when combined
      with pancreatic stenting. We need more such studies from other centers to confirm
      that the rare event of preoperative biliary and pancreatic stenting has indeed
      this harmful effect on healing of postoperative pancreatic anastomosis.

PMID- 29582022
TI  - Donor-acceptor cyclopropanes as ortho-quinone methide equivalents in formal (4 +
      2)-cycloaddition to alkenes.
AB  - A new type of donor-acceptor cyclopropane reactivity towards alkenes was revealed
      for 2-arylcyclopropane-1,1-diesters that contain an OH-group in the ortho
      position of the aryl substituent. In this case, the initial cyclopropanes
      participate in formal (4 + 2)-cycloaddition as synthetic equivalents of ortho
      quinone methides which are potential intermediates generated under mild
      conditions in the presence of a Lewis acid.

PMID- 29582023
TI  - Lewis acid-catalyzed enantiospecific [3 + 2] annulations of gamma-butyrolactone
      fused cyclopropanes with aromatic aldehydes: synthesis of chiral furanolignans.
AB  - An enantiospecific [3 + 2] annulation of gamma-butyrolactone fused cyclopropanes
      with aromatic aldehydes was realized under Lewis acid catalysis. This method
      provides facile access to a series of chiral furanolignan derivatives bearing
      multiple contiguous stereogenic centers in good-to-excellent yields, exclusive
      diastereoselectivities and excellent enantiopurities under mild reaction
      conditions. Elaboration work on the product of this reaction delivers
      stereoisomeric analogues of (+)-virgatusin and suggests a structural revision
      might be necessary for a previously reported isolated natural product.

PMID- 29582025
TI  - Tuning antimicrobial properties of biomimetic nanopatterned surfaces.
AB  - Nature has amassed an impressive array of structures that afford protection from
      microbial colonization/infection when displayed on the exterior surfaces of
      organisms. Here, controlled variation of the features of mimetics derived from
      etched silicon allows for tuning of their antimicrobial efficacy. Materials with
      nanopillars up to 7 MUm in length are extremely effective against a wide range of
      microbial species and exceed the performance of natural surfaces; in contrast,
      materials with shorter/blunter nanopillars (<2 MUm) selectively killed specific
      species. Using a combination of microscopies, the mechanisms by which bacteria
      are killed are demonstrated, emphasizing the dependence upon pillar density and
      tip geometry. Additionally, real-time imaging reveals how cells are immobilized
      and killed rapidly. Generic or selective protection from microbial colonization
      could be conferred to surfaces [for, e.g., internal medicine, implants (joint,
      dental, and cosmetic), food preparation, and the agricultural industry] patterned
      with these materials as coatings.

PMID- 29582024
TI  - Microscale mapping of extracellular matrix elasticity of mouse joint cartilage:
      an approach to extracting bulk elasticity of soft matter with surface roughness.
AB  - Cartilage is composed of cells and an extracellular matrix, the latter being a
      composite of a collagen mesh interpenetrated by proteoglycans responsible for
      tissue osmotic swelling. The matrix composition and structure vary through the
      tissue depth. Mapping such variability requires tissue sectioning to gain access.
      The resulting surface roughness, and concomitant proteoglycan loss contribute to
      large uncertainties in elastic modulus estimates. To extract elasticity values
      for the bulk matrix which are not obfuscated by the indeterminate surface layer,
      we developed a novel experimental and data analysis methodology. We analyzed the
      surface roughness to optimize the probe size, and performed high-resolution (1
      MUm) elasticity mapping on thin (~12 MUm), epiphyseal newborn mouse cartilage
      sections cut parallel to the bone longitudinal axis or normal to the articular
      surface. Mild fixation prevented the major proteoglycan loss observed in unfixed
      specimens but not the stress release that resulted in thickness changes in the
      sectioned matrix. Our novel data analysis method introduces a virtual contact
      point as a fitting parameter for the Hertz model, to minimize the effects of
      surface roughness and corrects for the finite section thickness. Our estimates of
      cartilage elasticity converge with increasing indentation depth and, unlike
      previous data interpretations, are consistent with linearly elastic material. A
      high cell density that leaves narrow matrix septa between cells may cause the
      underestimation of elastic moduli, whereas fixation probably causes an
      overestimation. The proposed methodology has broader relevance to nano- and micro
      indentation of soft materials with multiple length scales of organization and
      whenever surface effects (including roughness, electrostatics, van der Waals
      forces, etc.) become significant.

PMID- 29582026
TI  - Light trapping in thin film silicon solar cells via phase separated disordered
      nanopillars.
AB  - In this work, we have improved the absorption properties of thin film solar cells
      by introducing light trapping reflectors deposited onto self-assembled
      nanostructures. The latter consist of a disordered array of nanopillars and are
      fabricated by polymer blend lithography. Their broadband light scattering
      properties are exploited to enhance the photocurrent density of thin film
      devices, here based on hydrogenated amorphous silicon active layers. We
      demonstrate that these light scattering nanopillars yield a short-circuit current
      density increase of +33%rel with respect to equivalent solar cells processed on a
      planar reflector. Moreover, we experimentally show that they outperform randomly
      textured substrates that are commonly used for achieving efficient light
      trapping. Complementary optical simulations are conducted on an accurate 3D model
      to analyze the superior light harvesting properties of the nanopillar array and
      to derive general design rules. Our approach allows one to easily tune the
      morphology of the self-assembled nanostructures, is up-scalable and operated at
      room temperature, and is applicable to other photovoltaic technologies.

PMID- 29582027
TI  - On the phase control of CuInS2 nanoparticles from Cu-/In-xanthates.
AB  - In this paper we report the synthesis and single-crystal X-ray characterisation
      of six novel indium(iii) xanthate complexes. These xanthates have been used as an
      In-source for the synthesis of highly crystalline CuInS2 nanoparticles in
      conjunction with a Cu(i)-xanthate. In synthesising the nanoparticles we have also
      demonstrated an ability to control the phase of the material through choice of
      solvent.

PMID- 29582028
TI  - MOF-derived nanohybrids for electrocatalysis and energy storage: current status
      and perspectives.
AB  - More than 20 000 MOFs have been reported to date, with different combinations of
      metal ions/centers and organic linkers, and they can be grown into various 3D,
      2D, 1D and 0D morphologies. The flexibility in control over varying length scales
      from atomic scale up to bulk structure allows access to an almost endless variety
      of MOF-based and MOF-derived materials. Indeed, MOFs themselves have been studied
      as a class of useful functional materials. More remarkably, extensive research
      conducted in recent years has shown that MOFs are exceptionally good precursors
      for a large variety of nanohybrids as active materials in both electrocatalysis
      and energy storage. As they already contain both carbon and well-dispersed metal
      atoms, MOFs can be converted to conductive carbons decorated with active metal
      species and doping elements through appropriate pyrolysis. Due to the great
      diversity accessible in the composition, structure, and morphology of MOFs,
      several types of MOF-derived nanohybrids are now among the best performing
      materials both for electrocatalysts and electrodes in various energy conversion
      and storage devices. In addition to mesoporous nano-carbons, both doped and
      undoped, carbon-metal nanohybrids, and carbon-compound nanohybrids, there are
      several types of core@shell, encapsulated nanostructures, embedded nanosystems
      and heterostructures that have been developed from MOFs recently. They can be
      made in either free-standing forms, nano- or micro-powders, grown on appropriate
      conducting substrates, or assembled together with other active materials. During
      the MOF to active material conversion, other active species or precursors can be
      inserted into the MOF-derived nanostructures or assembled on surfaces, leading to
      uniquely new porous nanostructures. These MOF-derived active materials for
      electrocatalysis and energy storage are nanohybrids consisting of more than
      functional components that are purposely integrated together at desired length
      scales for much-improved performance. This article reviews the current status of
      these nanohybrids and concludes with a brief perspective on the future of MOF
      derived functional materials.

PMID- 29582029
TI  - Salen-indium/triarylborane triads: synthesis and ratiometric emission-colour
      changes by fluoride ion binding.
AB  - Salen-based indium triads, [{(3-tBu)2-(5-Mes2B)2-salen}In-Me] (1) and [{(3-tBu)2
      (5-Mes2Bphenyl)2-salen}In-Me] (2), bearing triarylborane (TAB) units were
      prepared and fully characterised by NMR spectroscopy and elemental analysis. The
      major absorption bands of 1 and 2 appeared in the region centred at 347 nm and
      374 nm, respectively, and the intense emission spectra were observed in the sky
      blue (lambdaem = 491 nm for 1) and bluish-green (lambdaem = 498 nm for 2)
      regions, respectively. The solvatochromism effects in various organic solvents
      and computational calculation results strongly suggested that these absorption
      and emission features are mainly attributed to intramolecular charge transfer
      (ICT) transitions between the salen ligand moieties and the TAB units.
      Furthermore, UV-vis and photoluminescence (PL) titration experiments by the
      addition of fluoride anions demonstrated ratiometric quenching patterns in both
      the absorption and emission spectra, indicating that binding of the fluoride
      anion to the boron centres interrupts these ICT transitions in each compound.
      Interestingly, both triads exhibited a gradual red-shifted response in each
      emission spectrum upon the addition of the fluoride anions, resulting in a
      dramatic colour-change to yellow. The computational calculation results of the S1
      states revealed that these emission-colour change properties arise from the
      elevation of HOMO levels, which are mainly localised on the TAB moieties,
      resulting from the fluoride anion binding to the borane centres.

PMID- 29582030
TI  - Does Rashba splitting in CH3NH3PbBr3 arise from 2 * 2 surface reconstruction?
AB  - As a result of early theoretical predictions, evidence for the Rashba or
      Dresselhaus effect in hybrid perovskites has recently attracted several
      experimental investigations, motivated by possible applications in spin
      orbitronics. For instance, a large Rashba splitting has recently been reported
      for the (001) surface of CH3NH3PbBr3. This effect is forbidden in the bulk
      material since both low-temperature and room-temperature crystal structures
      present inversion symmetry. Here we investigate the effects of two (001)
      nanoscale surface reconstructions of CH3NH3PbBr3 using first-principles
      approaches based on density functional theory (DFT). The two experimental
      reconstructions are related to different orientations of MA cations at the
      surface, defining zigzag and dimer phases. The impact of these structural
      transformations on their electronic structures is thoroughly investigated.
      Whereas calculations reveal the occurrence of surface-induced Rashba effect, its
      amplitude is considerably smaller than the experimentally reported value, in
      agreement with other experimental investigations and leading to the conclusion
      that mesoscale surface polar domains and/or surface defects may result from
      sample preparation.

PMID- 29582031
TI  - Variable temperature NMR of organogelators: the intensities of a single sample
      describe the full phase diagram.
AB  - Organogelators constitute a numerous class of compounds, able to form gels in
      organic solvents. Their phase diagrams are useful to understand their mechanisms
      of formation and their stability, but their mapping is often a tedious task. We
      show that liquid NMR can simplify and quicken the acquisition of phase diagrams.
      In liquid NMR spectra of organogels, the visible signals of the gelator represent
      only its soluble fraction. The intensities increase with temperature, until the
      gel melts. Suitable normalization of these intensities yields the solubility as a
      function of temperature, which is sufficient to map the phase diagram. We
      verified it experimentally with three organogelators, chosen because independent
      authors have previously mapped out their phase diagram by other techniques
      including DSC and rheology. We show that the curves obtained by NMR superimpose
      with these diagrams. A variable temperature NMR experiment with a single sample
      can yield the phase diagram with sensitivity of the order of 0.01 wt%.

PMID- 29582032
TI  - An in situ DRIFTS mechanistic study of CeO2-catalyzed acetylene semihydrogenation
      reaction.
AB  - CeO2-Catalyzed C2H2 semihydrogenation reaction is a newly emerging catalytic
      reaction, but the reaction mechanism is not established. We herein report a
      comprehensive mechanistic study by in situ diffuse reflectance infrared Fourier
      transformed spectroscopy. Various types of surface species were observed to form
      upon C2H2 and C2H4 adsorption on CeO2 at different temperatures, including
      molecularly-adsorbed pi-bonded and di-sigma-bonded species, dissociatively
      adsorbed species of C2H and C2H3, carbonates and formate species, and oligomers
      species, respectively. During the C2H2 semihydrogenation reaction, the CeO2
      surface is partially reduced and strongly hydroxylated. Both O and Ce sites on
      CeO2 are capable of catalyzing C2H2 semihydrogenation reaction to C2H4, and the O
      site is more active than the Ce site. The reaction mechanism was elucidated with
      observed molecularly-adsorbed C2H2 species, a C2H3 intermediate and adsorbed C2H4
      species on CeO2. The pi-bonded C2H2 species at the O site was identified as the
      dominant active surface species for CeO2-catalyzed C2H2 semihydrogenation
      reaction. These results greatly advance the fundamental understanding of CeO2
      catalyzed C2H2 semihydrogenation reaction.

PMID- 29582033
TI  - Refugee health - collaborating for better outcomes.

PMID- 29582034
TI  - Helping refugees build new lives: from consultation to collaboration.
AB  - Professor Peter Shergold was appointed as the New South Wales (NSW) Coordinator
      General for Refugee Resettlement in 2015, providing him with an opportunity to
      reimagine how the not-for-profit, public and private sectors could collaborate to
      improve the wellbeing of refugees settling in NSW, Australia. Through
      collaboration, NSW agencies are shifting the service response from one that is
      reactive to refugees' immediate settlement needs towards an investment approach
      that creates employment pathways. By identifying and building on refugees'
      strengths, resilience and human capital, Professor Shergold believes NSW can
      deliver better outcomes for both refugees and the communities they live in. PHRP
      asked him about his role, its objectives and its achievements.

PMID- 29582035
TI  - Integration of refugees into routine primary care in NSW, Australia.
AB  - Refugees have complex physical, psychological and social needs that are
      challenging to manage comprehensively in primary care. In recent years, many
      refugees settling in Australia have been sponsored by family members. Although
      they may receive settlement support, these new arrivals may not be assessed or
      managed by specialised refugee health services. Their sponsors usually link them
      to bilingual general practitioners, but these doctors may not be aware of or have
      access to a comprehensive range of services. There is an urgent need for more
      integrated health service provision for people from refugee backgrounds, based on
      trust and communication. This requires change at the practice, local service and
      system level.

PMID- 29582036
TI  - Canada's response to refugees at the primary health care level.
AB  - Responsive primary health care systems and services must be at once complex and
      nimble. Policy makers may wish to believe that existing health systems
      effectively care for all populations equally, including refugees. However, we
      know that refugees may require a health equity approach: an approach where all
      levels of government, all types of health practitioners, and even the public
      sector, participate to ensure access to effective primary health care. This
      article outlines some of Canada's healthcare responses for refugee populations.
      We provide field examples and guidelines that demonstrate responses, as well as
      ongoing inconsistencies and limitations. Refugee-receiving countries such as
      Australia, the US and Canada all have stories of success in resettlement and
      health systems. This article will focus on Canada.

PMID- 29582038
TI  - Transition from an asylum seeker-specific health service to mainstream primary
      care for community-based asylum seekers: a qualitative interview study.
AB  - BACKGROUND AND AIM: Transition of asylum seekers from special-purpose health
      services to mainstream primary care is both necessary and difficult. This study
      explores the issues encountered by asylum seekers undergoing this transition in
      Sydney, Australia. METHODS: Qualitative semistructured interviews were conducted
      with nine asylum seeker patients and nine staff working in the sector. RESULTS:
      Asylum seekers faced significant challenges in the transition to mainstream
      primary care. Contributing factors included the complexity of health and
      immigration systems, the way in which asylum seeker-specific services provide
      care, lack of understanding and accommodation by mainstream general practioner
      (GP) services, asylum seekers' own lack of understanding of the health system,
      mental illness, and social and financial pressures. CONCLUSIONS: There is a need
      for better preparation of asylum seekers for the transition to mainstream primary
      care. Mainstream GPs and other providers need more education and support so that
      they can better accommodate the needs of asylum seeker patients. This is an
      important role for Australia's refugee health services and Primary Health
      Networks.

PMID- 29582037
TI  - Blood screen findings in a 2-year cohort of newly arrived refugees to Sydney,
      Australia.
AB  - OBJECTIVES: To describe the prevalence of certain health conditions in newly
      arrived refugees to Sydney, Australia, and thereby help inform screening
      practices. STUDY TYPE: A clinical audit of routinely collected pathology results.
      METHODS: Demographics and pathology results from a nurse-led health assessment
      program for newly arrived refugees during 2013 and 2014 were analysed.
      Prevalences of screened conditions were calculated, and compared by country of
      birth and other demographic features. A specific category was created for those
      from Middle Eastern countries, for comparative analysis. RESULTS: Pathology
      results were analysed for 3307 people from 4768 seen by the assessment program
      (69.4%). Anaemia was found in 6% of males and 7.6% of females. Vitamin D
      deficiency (<50 nmol/L) was detected in 77.5%. Chronic hepatitis B was found in
      only 1.7% but in more than 10% of people from Burmese and Tibetan backgrounds.
      Strongyloides seropositivity was found in 4%. Among the subset tested for
      hepatitis C antibody, 0.5% were positive. No human immunodeficiency virus (HIV)
      infections were detected. More than 75% of the study population was from Middle
      Eastern countries. Compared with refugees from other regions, this subset had
      less anaemia (in females), more vitamin D deficiency, less chronic hepatitis B
      and less strongyloides seropositivity. CONCLUSIONS: People from refugee
      backgrounds have differing risks of conditions, based on demographics, migration
      history and prior screening. Postarrival testing should be tailored to each
      family and individual. Results of screening should be constantly reviewed and the
      approach updated based on findings. We support, in particular, the Canadian
      approach of only retesting HIV in refugees from countries with a high prevalence
      of infection (>1%).

PMID- 29582039
TI  - Violence against ambulance personnel: a retrospective cohort study of national
      data from Safe Work Australia.
AB  - : Objectives and importance: Paramedics have high rates of occupational injury
      and fatality. The objective of this study is to describe their specific risks of
      violence-related injury. STUDY TYPE: This retrospective cohort study is an
      examination of retrospective data provided by Safe Work Australia (SWA). METHODS:
      An examination of the 300 cases of serious claims of injury related to assaults,
      violence, harassment and bullying that occurred among individuals identified as
      ambulance officers and paramedics in Australia from 2001 to 2014. Paramedic risks
      likely vary by exposures such as hours worked and call volume. To examine how
      those exposures may influence risk, the available data were used to estimate
      rates based on hours worked and call volume. RESULTS: The data show that, for
      serious injuries among paramedics in Australia between 2001 and 2014, the total
      number of violence-related cases increased from 5 to 40 per year; the number of
      cases of injury secondary to assault tripled from 10 to 30; and the rate of cases
      by call volume doubled from 6 to 12. The cost of these injuries was approximately
      AUD$250 000 for the year 2013-14. The median time at work lost per individual
      case of 'work-related harassment and/or workplace bullying' was 9.6 weeks.
      Although females comprised 32% of the paramedic workforce, they were the victims
      in 42% of cases of exposure to violence and 40% of harassment cases. CONCLUSIONS:
      Although anecdotal reports indicate that some interventions have been attempted,
      violence against paramedics continues to be a growing problem in Australia. The
      data presented in this study allow for a better understanding of the problem and
      can support efforts by ambulance service administrators, physicians, paramedics
      and university researchers to work together to develop and publish evidence
      based, cost-effective solutions to reduce the risk of workplace violence.
      Effective solutions will likely be multifaceted and include training, engineering
      changes, community education and adjustments to agency policies. Because of the
      widespread nature of the risks, a national commission should be empowered to
      address this growing problem.

PMID- 29582040
TI  - Insights from linking routinely collected data across Australian health
      jurisdictions: a case study of end-of-life health service use.
AB  - OBJECTIVES: The jurisdictional nature of routinely collected health data in
      Australia has created challenges for linking data across state/territory and
      federal government boundaries. This has impeded understanding of the interplay
      between service use across hospital and community care. Our objective was to
      demonstrate the value-add of cross-jurisdictional data using a case study of
      health service use and the factors associated with healthcare use towards the end
      of life. STUDY TYPE: Retrospective cohort study using routinely collected health
      data. METHODS: We used two decedent cohorts of people aged >=65 years who died in
      New South Wales (NSW), Australia, in 2006 or 2007. The population cohort
      comprised the general NSW population linked to NSW data collections; the other
      cohort comprised Australian Government Department of Veterans' Affairs (DVA)
      clients (with full healthcare entitlements) linked to NSW and Commonwealth data.
      We compared information available on health services received during the last 6
      months of life and ran multivariable analyses for both cohorts to demonstrate the
      added value of the Commonwealth data. RESULTS: We included 37 567 decedents in
      the population cohort and 11 259 in the DVA cohort. Cancer was the cause of death
      for 27% of the NSW cohort and 22% of the DVA cohort; approximately 40% of
      decedents in each cohort had a cancer history. We summarise information on
      hospital services for both cohorts and examine community care (general
      practitioner consultations, specialist presentations, prescriptions dispensed)
      for the DVA cohort only. Multivariable analyses in the DVA cohort demonstrated
      that high rates of emergency department (ED) presentations and hospitalisation
      were associated with higher rates of use of all health services, including
      community care. Use of primary care did not reduce ED or hospital use. We were
      not able to examine the interplay between community and hospital care in the NSW
      population cohort. CONCLUSIONS: In our case study, we demonstrated the value-add
      of Commonwealth data for understanding the drivers of hospital services use,
      which has implications for service delivery and resource allocation. There is an
      abundance of routinely collected health data in Australia that can be used to
      describe whole-of-healthcare use for a broad range of issues.

PMID- 29582041
TI  - Psychostimulant-related health service demand in an inner-city hospital, 2012
      2015.
AB  - OBJECTIVE: To analyse routinely collected data from a hospital database of drug
      health consultation-liaison (CL) assessments. We aimed to investigate changes in
      psychostimulant-related health service demand in an inner-city hospital to inform
      the development of locally appropriate models of care. METHODS: We used de
      identified drug health CL service data from 2012 to 2015. Psychostimulant-related
      consultations and admissions were compared with opioid-related consultations and
      admissions over time, by sex and by ward type (medical units, mental health units
      or emergency department). RESULTS: The CL service collected information on 8800
      consultations and 4405 hospital admissions from 2012 to 2015. Psychostimulant use
      was responsible for 684 (7.8%) consultations and 372 (8.4%) admissions. Opioids
      were related to 1914 (21.8%) consultations and 864 (19.6%) admissions.
      Psychostimulants were the subject of three times more consultations in 2015 than
      in 2012, and more than twice as many admissions. Time trend analysis showed a
      significant time effect for consultations and admissions relating to
      psychostimulants. Conversely, no significant changes were observed in
      consultations and admissions relating to opioids. CONCLUSION: This study
      identified a rapid rise in the demand for psychostimulant-related inpatient
      assessments, suggesting the use of these drugs has increased locally. Because of
      the impact on the public health system, there is a need to invest in and
      implement new treatment strategies and services for psychostimulant users.

PMID- 29582043
TI  - Would Have-A Physician's Personal Reflection On Alzheimer Dementia.

PMID- 29582042
TI  - Intergovernmental collaboration for the health and wellbeing of refugees settling
      in Australia.
AB  - As outlined in the Department of Immigration and Border Protection Annual report
      2016-17, Australia granted 21 928 humanitarian visas in 2016-17, 13 760 of them
      offshore. This number will increase in future to a planned offshore program of 18
      750 in 2018-19. The report notes that the United Nations High Commissioner for
      Refugees ranks Australia third for the number of refugees resettled. With such a
      massive program and commitment by the Australian Government, the need to ensure
      that health and wellbeing are maintained or gained during the settlement process
      is paramount. This article outlines how collaboration between like-minded
      national governments can improve premigration health screening through
      information sharing, collaborative learning and increased capability in countries
      of origin to not only screen for illness and disability, but to more effectively
      put measures in place to address these before, during and after arrival.
      Australia, Canada, New Zealand, the UK and the US have worked together for more
      than a decade on migration health screening policies to ensure better management
      of health needs and successful resettlement. A case study about the Syrian
      refugee cohort, which began arriving in Australia in late 2015, illustrates how
      intergovernmental collaboration can improve settlement.

PMID- 29582044
TI  - Caution to Readers About Systematic Review on Vitamin K and Prevention of
      Fractures That Included Problematic Trials.

PMID- 29582045
TI  - Advertising and Youth.

PMID- 29582046
TI  - Caution of Conclusions of a Meta-analysis Including Problematic Trials.

PMID- 29582047
TI  - Global Prevalence of Fetal Alcohol Spectrum Disorder in Italy.

PMID- 29582048
TI  - Assessing Tremor and Adverse Events in Patients With Tremor-Dominant Parkinson
      Disease Undergoing Focused Ultrasound Thalamotomy-Reply.

PMID- 29582049
TI  - Gene Therapy in Alzheimer Disease-It May Be Feasible, but Will It Be Beneficial?

PMID- 29582050
TI  - Assessing Tremor and Adverse Events in Patients With Tremor-Dominant Parkinson
      Disease Undergoing Focused Ultrasound Thalamotomy.

PMID- 29582051
TI  - Implementing Evidence-Based Practice: Selecting Treatment Words to Boost
      Phonological Learning.
AB  - Purpose: Word selection has typically been thought of as an inactive ingredient
      in phonological treatment, but emerging evidence suggests that word selection is
      an active ingredient that can impact phonological learning. The goals of this
      tutorial are to (a) review the emerging single-subject evidence on the influence
      of word characteristics on phonological learning in clinical treatment, (b)
      outline hypotheses regarding the mechanism of action of word characteristics, and
      (c) provide resources to support clinicians incorporating word selection as an
      active ingredient in their approach to phonological treatment. Method: Research
      demonstrating the influence of the word frequency, neighborhood density, age of
      acquisition, and lexicality of treatment stimuli on phonological learning is
      summarized. The mechanism of action for each characteristic is hypothesized.
      Methods from the research studies are used to create a free set of evidence-based
      treatment materials targeting most of the mid-8 and late-8 consonants. Results:
      Clinicians have numerous evidence-based options to consider when selecting
      stimuli for phonological treatment including (a) high-frequency and high-density
      words, (b) low-frequency and high-density words, (c) high-frequency and mixed
      density words, (d) low-frequency and late-acquired words, and (e) nonwords.
      Conclusion: Incorporating word characteristics into phonological treatment may
      boost phonological learning. KU ScholarWorks Supplemental Material:
      http://hdl.handle.net/1808/24768.

PMID- 29582052
TI  - The Complexity Approach to Phonological Treatment: How to Select Treatment
      Targets.
AB  - Purpose: There are a number of evidence-based treatments for preschool children
      with phonological disorders (Baker & McLeod, 2011). However, a recent survey by
      Brumbaugh and Smit (2013) suggests that speech-language pathologists are not
      equally familiar with all evidence-based treatment alternatives, particularly the
      complexity approach. The goal of this clinical tutorial is to provide coaching on
      the implementation of the complexity approach in clinical practice, focusing on
      treatment target selection. Method: Evidence related to selecting targets for
      treatment based on characteristics of the targets (i.e., developmental norms,
      implicational universals) and characteristics of children's knowledge of the
      targets (i.e., accuracy, stimulability) is reviewed. Free resources are provided
      to aid clinicians in assessing accuracy and stimulability of singletons and
      clusters. Use of treatment target selection and generalization prediction
      worksheets is illustrated with 3 preschool children. Results: Clinicians can
      integrate multiple pieces of information to select complex targets and
      successfully apply the complexity approach to their own clinical practice.
      Conclusion: Incorporating the complexity approach into clinical practice will
      expand the range of evidence-based treatment options that clinicians can use when
      treating preschool children with phonological disorders. Supplemental Material
      S1: https://doi.org/10.23641/asha.6007562. KU ScholarWorks Supplemental Material:
      http://hdl.handle.net/1808/24767.

PMID- 29582053
TI  - Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With
      Alzheimer Disease: A Randomized Clinical Trial.
AB  - Importance: Nerve growth factor (NGF) is an endogenous neurotrophic factor that
      prevents the death and augments the functional state of cholinergic neurons of
      the basal forebrain, a cell population that undergoes extensive degeneration in
      Alzheimer disease (AD). Objective: To determine whether stereotactically guided
      intracerebral injections of adeno-associated viral vector (serotype 2)-nerve
      growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of
      impact on cognitive decline in mild to moderate AD-associated dementia. Design,
      Setting, and Participants: In a multicenter phase 2 trial, 49 participants with
      mild to moderate AD were randomly assigned in a 1:1 ratio to receive
      stereotactically guided intracerebral injections of AAV2-NGF or sham surgery.
      Participants were enrolled between November 2009 and December 2012. Analyses
      began in February 2015. The study was conducted at 10 US academic medical
      centers. Eligibility required a diagnosis of mild to moderate dementia due to AD
      and individuals aged 55 to 80 years. A total of 39 participants did not pass
      screening; the most common reason was Mini-Mental State Examination scores below
      cutoff. Analyses were intention-to-treat. Interventions: Stereotactically guided
      intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each
      hemisphere or sham surgery. Main Outcomes and Measures: Change from baseline on
      the Alzheimer's Disease Assessment Scale-cognitive subscale at month 24. Results:
      Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white,
      and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated
      through 24 months. No significant difference was noted between the treatment
      group and placebo on the primary outcome measure, the Alzheimer's Disease
      Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11
      [4.65], P = .17). Conclusions and Relevance: This multicenter randomized clinical
      trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene
      delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but
      did not affect clinical outcomes or selected AD biomarkers. Pathological
      confirmation of accurate gene targeting is needed. Trial Registration:
      clinicaltrials.gov Identifier NCT00876863.

PMID- 29582055
TI  - Osteopathic Medical Education: Answering the Call.

PMID- 29582054
TI  - Office-Based Screening for Dementia in Parkinson Disease: The Montreal Parkinson
      Risk of Dementia Scale in 4 Longitudinal Cohorts.
AB  - Importance: Parkinson disease dementia dramatically increases mortality rates,
      patient expenditures, hospitalization risk, and caregiver burden. Currently,
      predicting Parkinson disease dementia risk is difficult, particularly in an
      office-based setting, without extensive biomarker testing. Objective: To appraise
      the predictive validity of the Montreal Parkinson Risk of Dementia Scale, an
      office-based screening tool consisting of 8 items that are simply assessed.
      Design, Setting, and Participants: This multicenter study (Montreal, Canada;
      Tottori, Japan; and Parkinson Progression Markers Initiative sites) used 4
      diverse Parkinson disease cohorts with a prospective 4.4-year follow-up. A total
      of 717 patients with Parkinson disease were recruited between May 2005 and June
      2016. Of these, 607 were dementia-free at baseline and followed-up for 1 year or
      more and so were included. The association of individual baseline scale variables
      with eventual dementia risk was calculated. Participants were then randomly split
      into cohorts to investigate weighting and determine the scale's optimal cutoff
      point. Receiver operating characteristic curves were calculated and correlations
      with selected biomarkers were investigated. Main Outcomes and Measures: Dementia,
      as defined by Movement Disorder Society level I criteria. Results: Of the 607
      patients (mean [SD] age, 63.4 [10.1]; 376 men [62%]), 70 (11.5%) converted to
      dementia. All 8 items of the Montreal Parkinson Risk of Dementia Scale
      independently predicted dementia development at the 5% significance level. The
      annual conversion rate to dementia in the high-risk group (score, >5) was 14.9%
      compared with 5.8% in the intermediate group (score, 4-5) and 0.6% in the low
      risk group (score, 0-3). The weighting procedure conferred no significant
      advantage. Overall predictive validity by the area under the receiver operating
      characteristic curve was 0.877 (95% CI, 0.829-0.924) across all cohorts. A cutoff
      of 4 or greater yielded a sensitivity of 77.1% (95% CI, 65.6-86.3) and a
      specificity of 87.2% (95% CI, 84.1-89.9), with a positive predictive value (as of
      4.4 years) of 43.90% (95% CI, 37.76-50.24) and a negative predictive value of
      96.70% (95% CI, 95.01-97.85). Positive and negative likelihood ratios were 5.94
      (95% CI, 4.08-8.65) and 0.26 (95% CI, 0.17-0.40), respectively. Scale results
      correlated with markers of Alzheimer pathology and neuropsychological test
      results. Conclusions and Relevance: Despite its simplicity, the Montreal
      Parkinson Risk of Dementia Scale demonstrated predictive validity equal or
      greater to previously described algorithms using biomarker assessments. Future
      studies using head-to-head comparisons or refinement of weighting would be of
      interest.

PMID- 29582056
TI  - Educational Intervention in a Medically Underserved Area.
AB  - Context: Medical students from rural and medically underserved areas (MUAs) are
      more likely than their peers to practice medicine in rural areas and MUAs.
      However, students from MUAs are also more likely to face socioeconomic barriers
      to a career in medicine. Objective: To determine whether a week-long summer
      enrichment experience (SEE) at Edward Via College of Osteopathic Medicine
      Carolinas could successfully teach high school students from MUAs basic
      biomedical concepts and foster an interest in medicine and the health sciences.
      Methods: The SEE program is open to high school students in the Spartanburg,
      South Carolina, area. The program includes interactive lectures, laboratories,
      demonstrations on gross anatomy prosections, demonstrations on medical simulation
      models, tours of emergency vehicles, an introduction to osteopathic manipulative
      medicine, and student-led research projects. Participants were asked to complete
      a 15-question quiz that assessed their knowledge of basic biomedical concepts and
      a 10-question survey that assessed their attitudes toward careers in medicine and
      health sciences. Both the quiz and the survey were completed on both the first
      and final days of the program. The data were analyzed using paired t tests.
      Results: Participant knowledge of basic biomedical concepts, as determined by the
      quiz scores, increased after completion of the program (9.1 average correct
      answers vs 12.6 average correct answers) (P<.001). Participant attitude toward
      medicine and the health sciences improved in 9 of the 10 items surveyed after
      completion of the program (P<.05). Conclusions: Participant knowledge of basic
      biomedical concepts and their knowledge of and interest in careers in the health
      sciences improved after completing the SEE program. These findings suggest that
      educational interventions for high school students could help to develop primary
      care physicians for rural areas and MUAs and that there is a role for osteopathic
      medical schools to nurture these students as early as possible.

PMID- 29582057
TI  - Factors Associated With Osteopathic Primary Care Residency Choice Decisions.
AB  - Context: The osteopathic medical profession traditionally emphasized the
      education of primary care physicians. A common thread for both osteopathic and
      allopathic residency matches, however, has been an increase in the interest in
      specialties outside of primary care. Objective: To determine whether there are
      critical points in medical school associated with residency selection decision
      making, what factors affect residency selection decisions, and whether any
      identifiable shifts or trends exist. Methods: This mixed-methods study
      sequentially used qualitative and quantitative research approaches. The study
      population was a convenience sample of osteopathic medical students, interns and
      residents, and practicing physicians from partner medical schools, associated
      hospitals, and a regional association of osteopathic physicians. In the first
      phase, interviews and focus group discussions were analyzed for codes,
      categories, and themes relating to factors that influence residency selection. In
      the second phase, a survey was created from the results of the first phase and
      administered to study participants. Results: Of the 3450 potential participants,
      282 completed the survey. Ninety-one of 209 participants (43.5%) indicated that
      the third year of medical school was the time they will or did decide what type
      of residency program to pursue. There were no significant differences in the mean
      scores between the respondent groups (ie, students, residents, and physicians)
      when ranking the importance of the 10 influential factors associated with
      residency selection decision-making (P>.05 for all). Conclusion: The highest
      percentage of participants indicated the third year of medical school was the
      time that they made residency selection decisions regarding what specialty they
      were interested in entering. No shifts regarding the importance of specific
      primary care residency choice factors were found between training status of
      respondents.

PMID- 29582058
TI  - Interprofessional Collaborative Practice: Use of Simulated Clinical Experiences
      in Medical Education.
AB  - Context: Mastering the art of assessing interprofessional outcomes has been a
      topic of interest in academic research. Specifically, the Interprofessional
      Education Collaborative has been publishing thorough bodies of work that aim to
      strengthen teamwork among health professionals and reinforce competencies that
      will lead to better patient care. Objective: To determine osteopathic medical
      students' perceived effectiveness of simulated clinical experiences in
      cultivating interprofessional competencies with nursing students. Methods: Second
      year osteopathic medical students (classes of 2016 and 2017) and nursing students
      participated in a simulated clinical experience using a simulated patient
      mannequin. Students were assessed on clinical and humanistic skills using graded
      evaluations performed by faculty and actors portraying family members and given
      feedback on their performance. Evaluation grades were not analyzed. Students were
      asked to complete an anonymous survey that assessed their attitudes toward the
      collaborative experience. Results: A total of 743 medical students participated
      in the study-371 from the class of 2016 and 372 from the class of 2017.
      Incomplete surveys (1 from the class of 2016 and 3 from the class of 2017) were
      included in the analysis. Statistically significant differences were found
      between the 2 classes of medical students in their responses to 2 items. With
      regard to appropriate patient data collection, the ranked distribution of scores
      was significantly greater for the class of 2014-2015 than for the class of 2013
      2014 (mean rank, 389.3 vs 354.64, respectively; U=75,445.50; P=.017). For the
      item on effective communication with family members, the ranked distribution of
      scores was significantly greater for the class of 2014-2015 than for the class of
      2013-2014 (mean rank, 390.61 vs 353.34, respectively; U=75,928.50; P=.006).
      Overall, medical students reported feeling better prepared to care for real
      patients after the simulation. Conclusion: Simulated interprofessional
      experiences during the second year of medical school may help prepare students to
      collaborate with other health care professionals in a clinical setting, take care
      of patients, and communicate with patients' family members.

PMID- 29582059
TI  - Assessment Considerations for Core Entrustable Professional Activities for
      Entering Residency.
AB  - Context: In the process of analyzing entrustable professional activities (EPAs)
      for use in medical education, ten Cate and others identified challenges,
      including the need for valid and reliable EPA assessment strategies. Objective:
      To provide osteopathic medical schools with a database of assessment tools
      compiled from the literature to assist them with the development and
      implementation of robust, evidence-based assessment methods. Methods: MEDLINE,
      ERIC, PubMed, and other relevant databases were searched using MeSH keywords for
      articles outlining robust, evidence-based assessment tools that could be used in
      designing assessments for EPAs 1 through 6. Results: A total of 55 publications
      were included in content analysis and reporting. All but 2 of the assessment
      articles were conducted in an undergraduate or graduate medical education
      setting. The majority of the 55 articles related to assessment of competencies
      affiliated with EPA 2 (16 articles) and EPA 4 (15 articles). Four articles
      focused on EPA 3. Conclusion: Osteopathic medical schools can use this database
      of assessment tools to support the development of EPA-specific assessment plans
      that match the unique context and needs of their institution.

PMID- 29582060
TI  - Resident and Faculty Attitudes Toward Osteopathic-Focused Education.
AB  - Context: The transition period for the single accreditation system for graduate
      medical education under the Accreditation Council for Graduate Medical Education
      (ACGME) began on July 1, 2015, and will end June 30, 2020. As of February 5,
      2018, 82.6% of residency programs accredited by the American Osteopathic
      Association (AOA) have applied for or achieved ACGME accreditation and 160
      programs have applied for or achieved osteopathic recognition. Objective: To
      assess baseline attitudes of osteopathic and allopathic faculty and residents in
      AOA-accredited and dually accredited residency programs regarding the value of
      osteopathic-focused educational curricula and mentors. Methods: A survey was
      emailed to 60 program directors of AOA-accredited programs and dually accredited
      residency programs, some of which had obtained ACGME osteopathic recognition. The
      survey was to be completed by residents and faculty. Items were formulated to
      obtain baseline measurements regarding the level of awareness of osteopathic
      principles and practice (OPP), attitudes regarding osteopathic culture, and the
      weighted importance of aspects of the osteopathic curriculum. Principal
      components analysis with Varimax rotation was used. Comparison analysis was
      accomplished by either independent t tests for subscale scores or Mann-Whitney U
      tests for item-level scores. Results: A total of 327 people responded to the
      survey (115 faculty members, 211 residents, and 1 no response). Of the 60 program
      directors contacted, 53 replied with at least 1 program representative. One
      hundred twenty-nine of all 211 residents (61.7%), including 107 of 134
      osteopathic family medicine residents (79.9%), agreed that they intended to use
      OMT when in practice. The curricular component item with the lowest total survey
      score, indicating the highest-ranked level of importance, was the ability to work
      with osteopathic faculty (mean [SD], 1.98 [0.98]). Of the items measuring
      osteopathic awareness, statements with the strongest level of agreement from all
      respondents were "I have seen OMT performed on a patient or a peer" and "I am
      familiar with the basic tenets of OPP." Conclusion: Residents in AOA-accredited
      programs value osteopathic mentors and OMT, and they generally intend to use OMT
      when in practice. Respondents from programs with osteopathic recognition had more
      favorable attitudes toward osteopathic culture and curriculum than did
      respondents from programs without osteopathic recognition.

PMID- 29582061
TI  - Single Accreditation System Update: A Year of Progress.
AB  - In 2014, the American Osteopathic Association (AOA), the American Association of
      Colleges of Osteopathic Medicine, and the Accreditation Council for Graduate
      Medical Education (ACGME) agreed to establish a new, single accreditation system
      for graduate medical education in the United States. The 5-year transition
      period, from July 1, 2015, through June 30, 2020, gives AOA training programs
      time to apply for and receive ACGME accreditation before the AOA ceases its
      postdoctoral accreditation functions. This article discusses policies to protect
      osteopathic residents during training, addresses program size, reviews progress
      at the midpoint of the 5-year transition, and looks at next steps in the
      establishment of the single accreditation system.

PMID- 29582062
TI  - Appendix 1: Osteopathic Graduate Medical Education, 2018.

PMID- 29582063
TI  - Appendix 2: American Osteopathic Association Specialty Board Certification.

PMID- 29582064
TI  - Aortic Arch Mycotic Aneurysm.

PMID- 29582065
TI  - Bronchopulmonary Sequestration.

PMID- 29582066
TI  - Shared Journey in Medicine: Following in My Father's Footsteps.

PMID- 29582067
TI  - New Tobacco Products With Fewer Advertising Restrictions and Consequences for the
      Current Generation of Youths.

PMID- 29582068
TI  - Driving Under the Influence of Cannabis: An Increasing Public Health Concern.

PMID- 29582069
TI  - Global Prevalence of Fetal Alcohol Spectrum Disorder in Italy-Reply.

PMID- 29582070
TI  - Genomic Analysis to Avoid Misdiagnosis of Adults With Bilateral Renal Cysts.

PMID- 29582072
TI  - Balancing Innovation and Safety When Integrating Digital Tools Into Health Care.

PMID- 29582071
TI  - Vaccination Patterns in Children After Autism Spectrum Disorder Diagnosis and in
      Their Younger Siblings.
AB  - Importance: In recent years, rates of vaccination have been declining. Whether
      this phenomenon disproportionately affects children with autism spectrum disorder
      (ASD) or their younger siblings is unknown. Objectives: To investigate if
      children after receiving an ASD diagnosis obtain their remaining scheduled
      vaccines according to the Advisory Committee on Immunization Practices (ACIP)
      recommendations and to compare the vaccination patterns of younger siblings of
      children with ASD with the vaccination patterns of younger siblings of children
      without ASD. Design, Setting, and Participants: This investigation was a
      retrospective matched cohort study. The setting was 6 integrated health care
      delivery systems across the United States within the Vaccine Safety Datalink.
      Participants were children born between January 1, 1995, and September 30, 2010,
      and their younger siblings born between January 1, 1997, and September 30, 2014.
      The end of follow-up was September 30, 2015. Exposures: Recommended childhood
      vaccines between ages 1 month and 12 years. Main Outcome and Measure: The
      proportion of children who received all of their vaccine doses according to ACIP
      recommendations. Results: The study included 3729 children with ASD (676 [18.1%]
      female), 592 907 children without ASD, and their respective younger siblings.
      Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended
      between ages 4 and 6 years, children with ASD were significantly less likely to
      be fully vaccinated compared with children without ASD (adjusted rate ratio,
      0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were
      significantly lower among younger siblings of children with ASD compared with
      younger siblings of children without ASD. The adjusted rate ratios varied from
      0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old.
      Parents who had a child with ASD were more likely to refuse at least 1
      recommended vaccine for that child's younger sibling and to limit the number of
      vaccines administered during the younger sibling's first year of life.
      Conclusions and Relevance: Children with ASD and their younger siblings were
      undervaccinated compared with the general population. The results of this study
      suggest that children with ASD and their younger siblings are at increased risk
      of vaccine-preventable diseases.

PMID- 29582073
TI  - Ethical Obligations in Short-Term Global Health Clinical Experiences: The Devil
      Is in the Details.

PMID- 29582074
TI  - Enforcing Federal Drug Laws in States Where Medical Marijuana Is Lawful.

PMID- 29582076
TI  - Ethical Obligations Regarding Short-Term Global Health Clinical Experiences: An
      American College of Physicians Position Paper.
AB  - This American College of Physicians position paper aims to inform ethical
      decision making surrounding participation in short-term global health clinical
      care experiences. Although the positions are primarily intended for practicing
      physicians, they may apply to other health care professionals and should inform
      how institutions, organizations, and others structure short-term global health
      experiences. The primary goal of short-term global health clinical care
      experiences is to improve the health and well-being of the individuals and
      communities where they occur. In addition, potential benefits for participants in
      global health include increased awareness of global health issues, new medical
      knowledge, enhanced physical diagnosis skills when practicing in low-technology
      settings, improved language skills, enhanced cultural sensitivity, a greater
      capacity for clinical problem solving, and an improved sense of self-satisfaction
      or professional satisfaction. However, these activities involve several ethical
      challenges. Addressing these challenges is critical to protecting patient welfare
      in all geographic locales, promoting fair and equitable care globally, and
      maintaining trust in the profession. This paper describes 5 core positions that
      focus on ethics and the clinical care context and provides case scenarios to
      illustrate them.

PMID- 29582075
TI  - Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity:
      The Mobile Parkinson Disease Score.
AB  - Importance: Current Parkinson disease (PD) measures are subjective, rater
      dependent, and assessed in clinic. Smartphones can measure PD features, yet no
      smartphone-derived rating score exists to assess motor symptom severity in real
      world settings. Objectives: To develop an objective measure of PD severity and
      test construct validity by evaluating the ability of the measure to capture
      intraday symptom fluctuations, correlate with current standard PD outcome
      measures, and respond to dopaminergic therapy. Design, Setting, and Participants:
      This observational study assessed individuals with PD who remotely completed 5
      tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone
      application. We used a novel machine-learning-based approach to generate a mobile
      Parkinson disease score (mPDS) that objectively weighs features derived from each
      smartphone activity (eg, stride length from the gait activity) and is scaled from
      0 to 100 (where higher scores indicate greater severity). Individuals with and
      without PD additionally completed standard in-person assessments of PD with
      smartphone assessments during a period of 6 months. Main Outcomes and Measures:
      Ability of the mPDS to detect intraday symptom fluctuations, the correlation
      between the mPDS and standard measures, and the ability of the mPDS to respond to
      dopaminergic medication. Results: The mPDS was derived from 6148 smartphone
      activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56
      [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In
      addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%]
      women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women)
      completed in-clinic assessments. The mPDS detected symptom fluctuations with a
      mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The
      measure correlated well with the Movement Disorder Society Unified Parkinson
      Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P
      < .001), the Timed Up and Go assessment (r = 0.72; P = .002), and the Hoehn and
      Yahr stage (r = 0.91; P < .001). The mPDS improved by a mean (SD) of 16.3 (5.6)
      points in response to dopaminergic therapy. Conclusions and Relevance: Using a
      novel machine-learning approach, we created and demonstrated construct validity
      of an objective PD severity score derived from smartphone assessments. This score
      complements standard PD measures by providing frequent, objective, real-world
      assessments that could enhance clinical care and evaluation of novel
      therapeutics.

PMID- 29582077
TI  - Association of E-Cigarette Use With Smoking Cessation Among Smokers Who Plan to
      Quit After a Hospitalization: A Prospective Study.
AB  - Background: Many smokers report using e-cigarettes to help them quit smoking, but
      whether e-cigarettes aid cessation efforts is uncertain. Objective: To determine
      whether e-cigarette use after hospital discharge is associated with subsequent
      tobacco abstinence among smokers who plan to quit and are advised to use evidence
      based treatment. Design: Secondary data analysis of a randomized controlled
      trial. (ClinicalTrials.gov: NCT01714323 [parent trial]). Setting: 3 hospitals.
      Participants: 1357 hospitalized adult cigarette smokers who planned to stop
      smoking, received tobacco cessation counseling in the hospital, and were randomly
      assigned at discharge to a tobacco treatment recommendation (control) or free
      tobacco treatment (intervention). Measurements: Self-reported e-cigarette use
      (exposure) was assessed 1 and 3 months after discharge; biochemically validated
      tobacco abstinence (outcome) was assessed 6 months after discharge. Results:
      Twenty-eight percent of participants used an e-cigarette within 3 months after
      discharge. In an analysis of 237 propensity score-matched pairs, e-cigarette
      users were less likely than nonusers to abstain from tobacco use at 6 months
      (10.1% vs. 26.6%; risk difference, -16.5% [95% CI, -23.3% to -9.6%]). The
      association between e-cigarette use and quitting varied between intervention
      patients, who were given easy access to conventional treatment (7.7% vs. 29.8%;
      risk difference, -22.1% [CI, -32.3% to -11.9%]), and control patients, who
      received only treatment recommendations (12.0% vs. 24.1%; risk difference, -12.0%
      [CI, -21.2% to 2.9%]) (P for interaction = 0.143). Limitations: Patients self
      selected e-cigarette use. Unmeasured confounding is possible in an observational
      study. Conclusion: During 3 months after hospital discharge, more than a quarter
      of smokers attempting to quit used e-cigarettes, mostly to aid cessation, but few
      used them regularly. This pattern of use was associated with less tobacco
      abstinence at 6 months than among smokers who did not use e-cigarettes.
      Additional study is needed to determine whether regular use of e-cigarettes aids
      or hinders smoking cessation. Primary Funding Source: National Heart, Lung, and
      Blood Institute.

PMID- 29582079
TI  - 2017 Update on Pediatric Medical Overuse: A Review.
AB  - Importance: Medical overuse has historically focused on adult health care, but
      interest in how children are affected by medical overuse is increasing. This
      review examines important research articles published in 2016 that address
      pediatric overuse. Observations: A structured search of PubMed and a manual
      review of the tables of contents of 10 journals identified 169 articles related
      to pediatric overuse published in 2016, from which 8 were selected based on the
      quality of methods and potential harm to patients in terms of prevalence and
      magnitude. Articles were categorized by overtreatment, overmedicalization, and
      overdiagnosis. Findings included evidence of overtreatment with commercial
      rehydration solution, antidepressants, and parenteral nutrition;
      overmedicalization with planned early deliveries, immobilization of ankle
      injuries, and use of hydrolyzed infant formula; and evidence of overdiagnosis of
      hypoxemia among children recovering from bronchiolitis. Conclusions and
      Relevance: The articles were of high quality, with most based on randomized
      clinical trials. The potential harms associated with pediatric overuse were
      significant, including increased risk of infection, developmental disability, and
      suicidality.

PMID- 29582080
TI  - Creating a "Manageable Cockpit" for Clinicians: A Shared Responsibility.

PMID- 29582078
TI  - Association Between Receptivity to Tobacco Advertising and Progression to Tobacco
      Use in Youth and Young Adults in the PATH Study.
AB  - Importance: Cigarette marketing contributes to initiation of cigarette smoking
      among young people, which has led to restrictions on use of cigarette
      advertising. However, little is known about other tobacco advertising and
      progression to tobacco use in youth and young adults. Objective: To investigate
      whether receptivity to tobacco advertising among youth and young adults is
      associated with progression (being a susceptible never user or ever user) to use
      of the product advertised, as well as conventional cigarette smoking. Design,
      Setting, and Participants: The Population Assessment of Tobacco and Health (PATH)
      Study at wave 1 (2013-2014) and 1-year follow-up at wave 2 (2014-2015) was
      conducted in a US population-based sample of never tobacco users aged 12 to 24
      years from wave 1 of the PATH Study (N = 10 989). Household interviews using
      audio computer-assisted self-interviews were conducted. Exposures: Advertising
      for conventional cigarettes, electronic cigarettes (e-cigarettes), cigars, and
      smokeless tobacco products at wave 1. Main Outcomes and Measures: Progression to
      susceptibility or ever tobacco use at 1-year follow-up in wave 2. Results: Of the
      10 989 participants (5410 male [weighted percentage, 48.3%]; 5579 female
      [weighted percentage, 51.7%]), receptivity to any tobacco advertising at wave 1
      was high for those aged 12 to 14 years (44.0%; 95% confidence limit [CL], 42.6%
      45.4%) but highest for those aged 18 to 21 years (68.7%; 95% CL, 64.9%-72.2%). e
      Cigarette advertising had the highest receptivity among all age groups. For those
      aged 12 to 17 years, susceptibility to use a product at wave 1 was significantly
      associated with product use at wave 2 for conventional cigarettes, e-cigarettes,
      cigars, and smokeless tobacco products. Among committed never users aged 12 to 17
      years at wave 1, any receptivity was associated with progression toward use of
      the product at wave 2 (conventional cigarettes: adjusted odds ratio [AOR], 1.43;
      95% CL, 1.23-1.65; e-cigarettes: AOR, 1.62; 95% CL, 1.41-1.85; cigars: AOR, 2.01;
      95% CL, 1.62-2.49; and smokeless [males only]: AOR, 1.42; 95% CL, 1.07-1.89) and
      with use of the product (conventional cigarettes: AOR, 1.54; 95% CL, 1.03-2.32; e
      cigarettes: AOR, 1.45; 95% CL, 1.19-1.75; cigars: AOR, 2.07; 95% CL, 1.26-3.40).
      Compared with those not receptive to any product advertising, receptivity to e
      cigarette advertising, but not to cigarette advertising, was independently
      associated with those aged 12 to 21 years having used a cigarette at wave 2 (AOR,
      1.60; 95% CL, 1.08-2.38). Conclusions and Relevance: Receptivity to tobacco
      advertising was significantly associated with progression toward use in
      adolescents. Receptivity was highest for e-cigarette advertising and was
      associated with trying a cigarette.

PMID- 29582082
TI  - Use of E-Cigarettes Among Smokers Who Plan to Quit After a Hospitalization.

PMID- 29582081
TI  - Publicly Reported Readmission Measures and the Hospital Readmissions Reduction
      Program: A False Equivalence?

PMID- 29582083
TI  - Hemoptysis or Hematemesis?-The Importance of Professional Medical Interpretation:
      A Teachable Moment.

PMID- 29582085
TI  - Antibiotic Therapy Duration in US Adults With Sinusitis.

PMID- 29582086
TI  - Applicability of Publicly Reported Hospital Readmission Measures to Unreported
      Conditions and Other Patient Populations: A Cross-sectional All-Payer Study.
AB  - Background: Readmission rates after hospitalizations for heart failure (HF),
      acute myocardial infarction (AMI), and pneumonia among Medicare beneficiaries are
      used to assess quality and determine reimbursement. Whether these measures
      reflect readmission rates for other conditions or insurance groups is unknown.
      Objective: To investigate whether hospital-level 30-day readmission measures for
      publicly reported conditions (HF, AMI, and pneumonia) among Medicare patients
      reflect those for Medicare patients hospitalized for unreported conditions or non
      Medicare patients hospitalized with HF, AMI, or pneumonia. Design: Cross
      sectional. Setting: Population-based. Participants: Hospitals in the all-payer
      Nationwide Readmissions Database in 2013 and 2014. Measurements: Hospital-level
      30-day all-cause risk-standardized excess readmission ratios (ERRs) were compared
      for 3 groups of patients: Medicare beneficiaries admitted for HF, AMI, or
      pneumonia (Medicare reported group); Medicare beneficiaries admitted for other
      conditions (Medicare unreported group); and non-Medicare beneficiaries admitted
      for HF, AMI, or pneumonia (non-Medicare group). Results: Within-hospital
      differences in ERRs varied widely among groups. Medicare reported ratios differed
      from Medicare unreported ratios by more than 0.1 for 29% of hospitals and from
      non-Medicare ratios by more than 0.1 for 46% of hospitals. Among hospitals with
      higher readmission ratios, ERRs for the Medicare reported group tended to
      overestimate ERRs for the non-Medicare group but underestimate those for the
      Medicare unreported group. Limitation: Medicare groups and risk adjustment
      differed slightly from those used by the Centers for Medicare & Medicaid
      Services. Conclusion: Hospital ERRs, as estimated by Medicare to determine
      financial penalties, have poor agreement with corresponding measures for
      populations and conditions not tied to financial penalties. Current publicly
      reported measures may not be good surrogates for overall hospital quality related
      to 30-day readmissions. Primary Funding Source: Richard A. and Susan F. Smith
      Center for Outcomes Research in Cardiology.

PMID- 29582084
TI  - Dual Antiplatelet Therapy in Transient Ischemic Attack and Minor Stroke With
      Different Infarction Patterns: Subgroup Analysis of the CHANCE Randomized
      Clinical Trial.
AB  - Importance: Infarction patterns may serve as important imaging markers to assess
      the probability of stroke recurrence in transient ischemic attack (TIA) and minor
      stroke. However, it is unclear whether patients with different infarction
      patterns benefit differently from dual antiplatelet therapy. Objectives: To
      investigate whether infarction patterns can stratify the risk of recurrent stroke
      and whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone
      are consistent in different infarction patterns after TIA or minor stroke.
      Design, Setting, and Participants: In this prespecified imaging substudy of the
      Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events
      (CHANCE) randomized clinical trial, a total of 1342 patients with
      noncardioembolic TIA or minor stroke at 45 sites of CHANCE from October 1, 2009,
      to July 30, 2012, were included in this substudy. The final analysis was
      conducted on July 30, 2016, and included 1089 patients with required magnetic
      resonance imaging sequences. Infarction patterns were grouped into multiple acute
      infarctions (MAIs), single acute infarction (SAI), and no acute infarction (NAI)
      according to diffusion-weighted imaging. Main Outcomes and Measures: Primary and
      secondary efficacy outcomes were stroke recurrence and new clinical vascular
      event after 3 months, respectively. The safety outcome was moderate to severe
      bleeding risk after 3 months. Results: Among 1089 patients, the mean (SD) age was
      63.1 (10.7) years and 731 patients (65%) were men. Patients with MAIs (hazard
      ratio [HR], 5.8; 95% CI, 2.2-15.1; P < .001) and SAI (HR, 3.9; 95% CI, 1.5-10.5;
      P = .007) had higher risk of recurrent stroke than those with NAI after
      adjustment for potential confounders at 3-month follow-up. Stroke recurrence
      occurred in 15 (10.1%) and 25 (18.8%) of patients with MAIs administered
      clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 0.5; 95% CI,
      0.3-0.96; P = .04), 24 (8.9%) and 24 (8.5%) of patients with SAI administered
      clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.1; 95% CI,
      0.6-2.0; P = .71), and 3 (2.6%) and 2 (1.4%) of patients with NAI administered
      clopidogrel plus aspirin and placebo plus aspirin, respectively (HR, 1.7; 95% CI,
      0.3-11.1; P = .56), with P = .04 for treatment * infarction pattern interaction
      effect. Clopidogrel plus aspirin did not increase moderate to severe bleeding
      risk. Conclusions and Relevance: Infarction patterns can efficiently stratify the
      risk of recurrent stroke within 3 months of noncardioembolic TIA or minor
      ischemic stroke. Patients with MAIs received the most pronounced clinical benefit
      from dual antiplatelet therapy without increasing the risk of moderate to severe
      bleeding. However, even if after dual antiplatelet treatment, patients with MAIs
      still had a risk of stroke recurrence as high as those with SAI. Trial
      Registration: clinicaltrials.gov Identifier: NCT00979589.

PMID- 29582087
TI  - Promoting Conditional Use of Communication Skills for Learners With Complex
      Communication Needs: A Tutorial.
AB  - Purpose: Conditional use of communication skills refers to the ability of a
      learner to appropriately generalize and discriminate when, where, and how to
      communicate based on constant variation and shifts in environmental cues. Method:
      We describe discrimination and generalization challenges encountered by learners
      with complex communication needs and ways in which these challenges are fostered
      through traditional communication intervention programming. We address
      arrangements in instruction that maximize the probability of learners acquiring
      the conditional use of new vocabulary and the modest instructional technology
      implemented when planning for generalization. Results: We propose establishing
      well-discriminated and generalized use of new vocabulary items through the
      application of a general case instruction framework to communication intervention
      programming. Conclusion: We provide intervention methodology, including
      intervention steps for general case instruction, a plethora of functional
      examples, and graphic displays to assess and intervene to promote conditional use
      of communication skills for learners with complex communication needs.

PMID- 29582088
TI  - Alcohol-Related Nurse Care Management in Primary Care: A Randomized Clinical
      Trial.
AB  - Importance: Experts recommend that alcohol use disorders (AUDs) be managed in
      primary care, but effective approaches are unclear. Objective: To test whether 12
      months of alcohol care management, compared with usual care, improved drinking
      outcomes among patients with or at high risk for AUDs. Design, Setting, and
      Participants: This randomized clinical trial was conducted at 3 Veterans Affairs
      (VA) primary care clinics. Between October 11, 2011, and September 30, 2014, the
      study enrolled 304 outpatients who reported heavy drinking (>=4 drinks per day
      for women and >=5 drinks per day for men). Interventions: Nurse care managers
      offered outreach and engagement, repeated brief counseling using motivational
      interviewing and shared decision making about treatment options, and nurse
      practitioner-prescribed AUD medications (if desired), supported by an
      interdisciplinary team (CHOICE intervention). The comparison was usual primary
      care. Main Outcomes and Measures: Primary outcomes, assessed by blinded telephone
      interviewers at 12 months, were percentage of heavy drinking days in the prior 28
      days measured by timeline follow-back interviews and a binary good drinking
      outcome, defined as abstinence or drinking below recommended limits in the prior
      28 days (according to timeline follow-back interviews) and no alcohol-related
      symptoms in the past 3 months as measured by the Short Inventory of Problems.
      Results: Of 304 participants, 275 (90%) were male, 206 (68%) were white, and the
      mean (SD) age was 51.4 (13.8) years. At baseline, both the CHOICE intervention (n
      = 150) and usual care (n = 154) groups reported heavy drinking on 61% of days
      (95% CI, 56%-66%). During the 12-month intervention, 137 of 150 patients in the
      intervention group (91%) had at least 1 nurse visit, and 77 of 150 (51%) had at
      least 6 nurse visits. A greater proportion of patients in the intervention group
      than in the usual care group received alcohol-related care: 42% (95% CI, 35%-49%;
      63 of 150 patients) vs 26% (95% CI, 19%-35%; 40 of 154 patients). Alcohol-related
      care included more AUD medication use: 32% (95% CI, 26%-39%; 48 of 150 patients
      in the intervention group) vs 8% (95% CI, 5%-13%; 13 of 154 patients in the usual
      care group). No significant differences in primary outcomes were observed at 12
      months between patients in both groups. The percentages of heavy drinking days
      were 39% (95% CI, 32%-47%) and 35% (95% CI, 28%-42%), and the percentages of
      patients with a good drinking outcome were 15% (95% CI, 9%-22%; 18 of 124
      patients) and 20% (95 % CI, 14%-28%; 27 of 134 patients), in the intervention and
      usual care groups, respectively (P = .32-.44). Findings at 3 months were similar.
      Conclusions and Relevance: The CHOICE intervention did not decrease heavy
      drinking or related problems despite increased engagement in alcohol-related
      care. Trial Registration: clinicaltrials.gov Identifier: NCT01400581.

PMID- 29582089
TI  - Urogenital symptoms: prevalence, bother, associations and impact in 22 year-old
      women of the Raine Study.
AB  - INTRODUCTION AND HYPOTHESIS: Urogenital symptoms are prevalent in older women,
      but there is little data available on the prevalence, bother, impact and
      associations with low back pain (LBP), obesity, parity, mental health (MH) and
      quality of life (QOL) in young women. Our aim was to determine the prevalence,
      bother and impact of urogenital symptoms and to explore associations with LBP,
      obesity, parity, MH and QOL in 22 year-old women. METHODS: This was a cross
      sectional evaluation using data collected from 588 women in the Raine Study, a
      pregnancy cohort in which participants have been regularly followed up from birth
      until 22 years. Data was analysed using descriptive statistics, univariate
      comparisons and linear regression models. RESULTS: Prevalence of urogenital
      symptoms were stress urinary incontinence (SUI) 6.3%, mixed urinary incontinence
      (MUI) 11.5%, leakage of drops 5.8%, urge urinary incontinence (UUI) 5.3%,
      bothersome urinary frequency 41.5%, difficulty emptying 11.8% and urogenital pain
      22.9%. Urinary frequency, MUI, difficulty emptying and urogenital pain were most
      bothersome, whilst difficulty emptying and urogenital pain were associated with
      greatest impact. Urinary frequency, SUI, leakage of drops, difficulty emptying
      and urogenital pain were associated with current LBP and LBP ever. Difficulty
      emptying and urogenital pain were associated with chronic LBP. Urogenital
      symptoms were not associated with obesity or parity. Women with urogenital
      symptoms had significantly poorer scores on the Mental Component Score of the
      Short Form Health Survey (SF)-12 and all aspects of the Depression Anxiety Stress
      Score. CONCLUSIONS: Urogenital symptoms are prevalent in young women, bothersome
      for some and are associated with LBP, poorer MH and reduced QOL.

PMID- 29582090
TI  - [Can a supraglottic airway device really be avoided during resuscitation?]

PMID- 29582091
TI  - [A close web-based patient follow-up improves overall survival in lung cancer
      patients].

PMID- 29582092
TI  - Particulate matter 2.5 damages skin cells by inducing oxidative stress,
      subcellular organelle dysfunction, and apoptosis.
AB  - The skin is the largest organ of the human body and the one mostly exposed to
      outdoor contaminants. To evaluate the biological mechanisms underlying skin
      damage caused by fine particulate matter (PM2.5), we analyzed the effects of
      PM2.5 on cultured human keratinocytes and the skin of experimental animals. PM2.5
      was applied to human HaCaT keratinocytes at 50 ug/mL for 24 h and to mouse skin
      at 100 ug/mL for 7 days. The results indicate that PM2.5 induced oxidative stress
      by generating reactive oxygen species both in vitro and in vivo, which led to DNA
      damage, lipid peroxidation, and protein carbonylation. As a result, PM2.5 induced
      endoplasmic reticulum stress, mitochondrial swelling, and autophagy, and caused
      apoptosis in HaCaT cells and mouse skin tissue. The PM2.5-induced cell damage was
      attenuated by antioxidant N-acetyl cysteine, confirming that PM2.5 cellular
      toxicity was due to oxidative stress. These findings contribute to understanding
      of the pathophysiological mechanisms triggered in the skin by PM2.5, among which
      oxidative stress may play a major role.

PMID- 29582094
TI  - BlaOXA-10 and PSE-1 Genes Located on Class 1 Integrons in Gallibacterium anatis.

PMID- 29582093
TI  - Inflammation, a significant player of Ataxia-Telangiectasia pathogenesis?
AB  - INTRODUCTION: Ataxia-Telangiectasia (A-T) syndrome is an autosomal recessive
      neurodegenerative disorder characterized by cerebellar ataxia, oculocutaneous
      telangiectasia, immunodeficiency, chromosome instability, radiosensitivity, and
      predisposition to malignancy. There is growing evidence that A-T patients suffer
      from pathologic inflammation that is responsible for many symptoms of this
      syndrome, including neurodegeneration, autoimmunity, cardiovascular disease,
      accelerated aging, and insulin resistance. In addition, epidemiological studies
      have shown A-T heterozygotes, somewhat like deficient patients, are susceptible
      to ionizing irradiation and have a higher risk of cancers and metabolic
      disorders. AREA COVERED: This review summarizes clinical and molecular findings
      of inflammation in A-T syndrome. CONCLUSION: Ataxia-Telangiectasia Mutated (ATM),
      a master regulator of the DNA damage response is the protein known to be
      associated with A-T and has a complex nuclear and cytoplasmic role. Loss of ATM
      function may induce immune deregulation and systemic inflammation.

PMID- 29582096
TI  - Living with systemic lupus erythematosus in the developing world.
AB  - Most of our understanding of SLE and its negative impact originates from
      developed countries. This review aims to collate existing literature on Health
      Related Quality of Life (HRQoL) in SLE patients living in developing countries to
      identify the gaps for the focus of future research. A narrative literature review
      was compiled using selected MeSH terms to search EBSCOHOST for articles published
      between January 1975 and February 2018 pertaining to HRQoL in SLE patients in
      developing countries. 31 studies from 11 countries were included for analysis.
      Only one longitudinal, one randomized controlled trial (RCT), one qualitative
      study, and two intervention studies were found. High disease activity and organ
      damage were associated with poor functional ability, mental health and low socio
      economic status (SES). Poor SES is a recurring theme in developing countries, and
      worsens all SLE outcomes by reducing access to healthcare, mental, social and
      emotional support systems. In developing countries, SLE has a globally negative
      impact on patients' HRQoL, similar to that seen in developed countries. There is
      an urgent need for more HRQoL studies, and in particular, longitudinal,
      qualitative and interventional studies in these countries to investigate unmet
      needs, and to explore novel strategies to improve patient outcomes.

PMID- 29582095
TI  - Physician-patient communication in rheumatology: a systematic review.
AB  - The nature of physician-patient interaction can have a significant impact on
      patient outcomes through information-sharing and disease-specific education that
      can enhance patients' active involvement in their care. The aim of this
      systematic review was to examine all the empirical evidence pertaining to aspects
      of physician-patient communication and its impact on patient outcomes. A
      systematic search of five electronic databases (MEDLINE, PsycINFO, EMBASE,
      CINAHL, and Web of Science) was undertaken from earliest record to December 2016.
      Studies were eligible if they: (1) included adult participants (18 years or over)
      with a diagnosis of a rheumatic condition; (2) were of quantitative, qualitative
      or mixed methods design; (4) were surveys, observational and interventional
      studies; (5) were published in the English language; and (6) reported findings on
      either various physician-patient communication aspects alone or in combination
      with physical and psychological outcomes. Searches identified 455 papers.
      Following full-text retrieval and assessment for eligibility and quality, ten
      studies were included in the review; six quantitative, one mixed methods, and
      three qualitative papers. Higher levels of trust in the physician and active
      patient participation in the medical consultation were linked to lower disease
      activity, better global health, less organ damage accrual, greater treatment
      satisfaction with fewer side effects from the medication, more positive beliefs
      about control over the disease, and about current and future health. Future
      research could focus on the design and implementation of interventions
      incorporating communications skills and patient-education training.

PMID- 29582097
TI  - Native rotational knee kinematics is restored after lateral UKA but not after
      medial UKA.
AB  - PURPOSE: The aim of this study was to compare the intraoperative kinematics of
      medial and lateral unicompartmental knee arthroplasty (UKA) with those of the
      native knee using a navigation system. METHODS: Six fresh-frozen cadaveric knees
      were included in the study. Medial UKA was performed in all right knees and
      lateral UKA was performed in all left knees. All UKA procedures were performed
      with a computerised navigation system. The tibial internal rotation angle and
      coronal alignment of the mechanical axis during passive knee flexion were
      assessed as rotational and varus/valgus kinematics before and after surgery using
      the navigation system. RESULTS: The rotation angles of the tibia in the early
      flexion phase of medial UKA were significantly larger than those of native knees
      (p = 0.008 at minimum knee flexion, p = 0.008 at 0 degrees  knee flexion). The
      rotational kinematics of lateral UKA was similar to those of the native knees
      throughout knee flexion. There were no significant differences in varus/valgus
      kinematics between native and UKA knees. CONCLUSION: The rotational kinematics of
      the native knee was not restored after medial UKA but was preserved after lateral
      UKA. There were no significant differences in the varus/valgus kinematics after
      either medial or lateral UKA when compared with those of the native knees. Thus,
      the geometry of the medial tibial articular surface is a determinant of the
      ability to restore the rotational kinematics of the native knee. Surgeons and
      implant designers should be aware that the anatomical medial articular geometry
      is an important factor in restoration of the native knee kinematics after knee
      arthroplasty.

PMID- 29582098
TI  - High reported rate of return to play following bone marrow stimulation for
      osteochondral lesions of the talus.
AB  - PURPOSE: The purpose of this study is to systematically review the literature and
      to evaluate the reported rehabilitation protocols, return to play guidelines and
      subsequent rates and timing of return to play following bone marrow stimulation
      (BMS) for osteochondral lesions of the talus (OLT). METHODS: MEDLINE, EMBASE and
      the Cochrane Library were searched according to the PRISMA guidelines in
      September 2017. The rate and timing of return to play was assessed. The
      rehabilitation protocols were recorded, including time to start range of motion,
      partial weight-bearing and complete weight-bearing. RESULTS: Fifty-seven studies
      with 3072 ankles were included, with a mean age of 36.9 years (range 23-56.8
      years), and a mean follow-up of 46.0 months (range 1.5-141 months). The mean rate
      of return to play was 86.8% (range 60-100%), and the mean time to return to play
      was 4.5 months (range 3.5-5.9 months). There was large variability in the
      reported rehabilitation protocols. Range of motion exercises were most often
      allowed to begin in the first week (46.2%), and second week postoperatively
      (23.1%). The most commonly reported time to start partial weight-bearing was the
      first week (38.8%), and the most frequently reported time of commencing full
      weight-bearing was 6 weeks (28.8%). Surgeons most often allowed return to play at
      4 months (37.5%). CONCLUSIONS: There is a high rate of return following BMS for
      OLT with 86.8% and the mean time to return to play was 4.5 months. There is also
      a significant deficiency in reported rehabilitation protocols, and poor quality
      reporting in return to play criteria. Early weightbearing and early postoperative
      range of motion exercises appear to be advantageous in accelerated return to
      sports. LEVEL OF EVIDENCE: Level IV.

PMID- 29582099
TI  - [Paths to the professional and responsible use of antibiotics].
AB  - Germany's position on prescribing antibiotics is among the lower third in Europe.
      There are some countries that prescribe remarkably fewer antibiotics. In Germany,
      the number of out-patient antibiotic prescriptions is too high for patients with
      low-grade infections and non-bacterial infections. Often, broad-spectrum
      antibiotics are prescribed instead of narrow-spectrum antibiotics. For in
      patients, perioperative prophylaxis is given for too long.In this article,
      different ways to reduce antibiotic prescriptions are introduced. Recommendations
      are given to improve the quality of therapy, implementation of diagnostics and
      scores, as well as information for physicians and patients.In this regard, an
      unsystematic literature search was done.To optimise the quality of prescribing,
      antibiotic checklists should be used. The important initial questions are if
      there is a bacterial infection and if antibiotic therapy is necessary. To apply
      diagnostics correctly is essential. Antibiotic use can be shortened or in some
      cases totally omitted if point-of-care tests (POCTs) are applied correctly.
      Species identification and resistance testing are essential for quality
      assurance. S3-guidelines are central for modern evidence-based medicine. Another
      key factor is good communication within the team and with patients. All
      measurements, like the application of POCTs, back-up prescribing, and prescribing
      an antibiotic, have to be communicated in a clear and sensitive way.

PMID- 29582100
TI  - The impact of time to catheter removal on short-, intermediate- and long-term
      urinary continence after radical prostatectomy.
AB  - PURPOSE: To assess the impact of prolonged catheterization time on 1-week (short
      term), 3-month (intermediate-term) and 1-year (long-term) UC. METHODS: Between
      2008 and 2015, 6918 men underwent RP by four high-volume surgeons. Exclusion
      criteria were baseline urinary incontinence (UI) and radiotherapy prior or within
      12 months after RP. For the remaining 4111 patients, data on short-, intermediate
      and long-term UC were available for 3989, 2490 and 1967 patients, respectively.
      UC was defined as the use of zero or 1-safety pad/24 h. Time to catheter removal
      was categorized into  <= 7, 8-14 and  >= 15 days. To assess the impact of
      catheterization time on short-, intermediate- and long-term UI, uni- and
      multivariable logistic regression analyses adjusted for age, BMI, prostate
      volume, pathological tumor stage, Charlson comorbidity index and nerve-sparing
      technique were performed. RESULTS: Post-RP UC rates at 1 week for catheterization
      of  <= 7, 8-14 and >= 15 days were 31.2, 27.4 and 18.0%. For the same groups, 3
      month and 1-year UC rates were 82.7, 79.2 and 74.1% as well as 90.8, 91.6 and
      88.2%, respectively. In multivariate logistic regressions, longer catheterization
      time was associated with worse short- and intermediate UI (OR 15 days: 2.19 and
      1.54; p = <= 0.001 and p = 0.04). This difference dissipated at 1 year after RP
      (p > 0.05). CONCLUSIONS: While longer catheterization is associated with worse
      short- and intermediate-term UC, it has no adverse impact on long-term UC.

PMID- 29582101
TI  - Agromyces mangrovi sp. nov., a novel actinobacterium isolated from the
      rhizosphere of a mangrove.
AB  - A novel actinobacterium, designated HIr16-25T, was isolated from the rhizosphere
      soil of a mangrove growing on Iriomote Island in Japan. Phylogenetic analysis
      based on 16S rRNA gene sequences revealed that strain HIr16-25T fell within the
      cluster of the members of the genus Agromyces and the highest sequence similarity
      value was observed with Agromyces rhizospherae IFO 16236T (98.6%). Strain HIr16
      25T possessed L-2,4-diaminobutyric acid as a diagnostic diamino acid of the
      peptidoglycan, and MK-12 and MK-11 as the predominant menaquinones. The major
      fatty acids were identified as iso-C16:0, anteiso-C15:0 and anteiso-C17:0 and the
      principal polar lipids were phosphatidylglycerol and one glycolipid. These
      chemotaxonomic features matched well those described for the members of the genus
      Agromyces. Meanwhile, the result of DNA-DNA hybridization and the presence of
      differential phenotypic characteristics between strain HIr16-25T and the type
      strain of A. rhizospherae indicated that strain HIr16-25T be classified as a
      novel species of the genus Agromyces. Therefore, we propose strain HIr16-25T to
      represent a novel species of the genus Agromyces, with the name Agromyces
      mangrovi sp. nov. The type strain is HIr16-25T (= NBRC 112812T = TBRC 7760T).

PMID- 29582102
TI  - Correction to: Depression Induced by Total Mastectomy, Breast Conserving Surgery
      and Breast Reconstruction: A Systematic Review and Meta-analysis.
AB  - The following grant funding information was omitted from the original article.

PMID- 29582103
TI  - Correction to: The hidden therapist: evidence for a central role of music in
      psychedelic therapy.
AB  - The article The hidden therapist: evidence for a central role of music in
      psychedelic therapy, written by Mendel Kaelen, Bruna Giribaldi, Jordan Raine,
      Lisa Evans, Christopher Timmerman, Natalie Rodriguez, Leor Roseman, Amanda
      Feilding, David Nutt, Robin Carhart-Harris, was originally published
      electronically on the publisher's internet portal.

PMID- 29582104
TI  - Practices of shake-flask culture and advances in monitoring CO2 and O2.
AB  - About 85 years have passed since the shaking culture was devised. Since then,
      various monitoring devices have been developed to measure culture parameters. O2
      consumed and CO2 produced by the respiration of cells in shaking cultures are of
      paramount importance due to their presence in both the culture broth and
      headspace of shake flask. Monitoring in situ conditions during shake-flask
      culture is useful for analysing the behaviour of O2 and CO2, which interact
      according to Henry's law, and is more convenient than conventional sampling that
      requires interruption of shaking. In situ monitoring devices for shake-flask
      cultures are classified as direct or the recently developed bypass type. It is
      important to understand the characteristics of each type along with their
      unintended effect on shake-flask cultures, in order to improve the existing
      devices and culture conditions. Technical developments in the bypass monitoring
      devices are strongly desired in the future. It is also necessary to understand
      the mechanism underlying conventional shake-flask culture. The existing shaking
      culture methodology can be expanded into next-generation shake-flask cultures
      constituting a novel culture environment through a judicious selection of
      monitoring devices depending on the intended purpose of shake-flask culture.
      Construction and sharing the databases compatible with the various types of the
      monitoring devices and measurement instruments adapted for shaking culture can
      provide a valuable resource for broadening the application of cells with shake
      flask culture.

PMID- 29582105
TI  - Microbial Decomposer Dynamics: Diversity and Functionality Investigated through a
      Transplantation Experiment in Boreal Forests.
AB  - Litter decomposition is the main source of mineral nitrogen (N) in terrestrial
      ecosystem and a key step in carbon (C) cycle. Microbial community is the main
      decomposer, and its specialization on specific litter is considered at the basis
      of higher decomposition rate in its natural environment than in other forests.
      However, there are contrasting evidences on how the microbial community responds
      to a new litter input and if the mass loss is higher in natural environment. We
      selected leaf litter from three different plant species across three sites of
      different altitudinal ranges: oak (Quercus petraea (Matt.) Liebl., 530 m a.s.l),
      beech (Fagus sylvatica L., 1000 m a.s.l.), rhododendron (Rhododendron ferrugineum
      L., 1530 m a.s.l.). A complete transplantation experiment was set up within the
      native site and the other two altitudinal sites. Microbial community structure
      was analyzed via amplified ribosomal intergenic spacer analysis (ARISA)
      fingerprinting. Functionality was investigated by potential enzyme activities.
      Chemical composition of litter was recorded. Mass loss showed no faster
      decomposition rate on native site. Similarly, no influence of site was found on
      microbial structure, while there was a strong temporal variation. Potential
      enzymatic activities were not affected by the same temporal pattern with a
      general increase of activities during autumn. Our results suggested that no
      specialization in microbial community is present due to the lack of influence of
      the site in structure and in the mass loss dynamics. Finally, different temporal
      patterns in microbial community and potential enzymatic activities suggest the
      presence of functional redundancy within decomposers.

PMID- 29582106
TI  - Trends and variations in the prescribing of secondary preventative cardiovascular
      therapies for non-ST elevation myocardial infarction (NSTEMI) in Malaysia.
AB  - PURPOSE: Information is lacking on prescribing of preventative cardiovascular
      pharmacotherapies for patients with non-ST elevation myocardial infarction
      (NSTEMI) in the Asian region. This study examined the prescribing rate of these
      pharmacotherapies, comparing NSTEMI to STEMI, and variations across demographics
      and clinical factors within the NSTEMI group in the multi-ethnic Malaysian
      population. METHODS: This is a retrospective analysis of the Malaysian National
      Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006
      to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP
      antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta
      blockers. Multivariate logistic regression was used to calculate adjusted odds
      ratio of receiving individual pharmacotherapies according to patients'
      characteristics in NSTEMI patients (n = 11,390). RESULTS: Prescribing rates for
      cardiovascular pharmacotherapies had significantly increased especially for ADP
      antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and
      antiplatelets but rates remained significantly lower compared to STEMI. Women and
      those over 65 years old were less likely to be prescribed these pharmacotherapies
      compared to men and younger NSTEMI patients. Chinese and Indians were more likely
      to receive selected pharmacotherapies compared to Malays (main ethnicity).
      Geographical variations were observed; East Malaysian (Malaysian Borneo) patients
      were less likely to receive these compared to Western region of Malaysian
      Peninsular. Underprescribing in patients with risk factors such as diabetes were
      observed with other co-morbidities influencing prescribing selectively.
      CONCLUSION: This study uncovers demographic and clinical variations in
      cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by
      policy makers, specialty societies, and physicians are required focusing on
      elderly, women, Malays, East Malaysians, and high-risk patients.

PMID- 29582107
TI  - Effects of stimulus pair orientation and hand switching on reaction time
      estimates of interhemispheric transfer.
AB  - Two behavioral estimates of interhemispheric transfer time, the crossed-uncrossed
      difference (CUD) and the unilateral field advantage (UFA), are thought to,
      respectively, index transfer of premotor and visual information across the corpus
      callosum in neurotypical participants. However, no attempt to manipulate visual
      and motor contingencies in a set of tasks while measuring the CUD and the UFA has
      yet been reported. In two go/no-go comparison experiments, stimulus pair
      orientations were manipulated. The hand of response changed after each correct
      response in the second, but not the first experiment. No correlation was found
      between the CUD and the UFA, supporting the hypothesis that these two measures
      index different types of information transfer across hemispheres. An effect of
      manipulation of stimulus pair orientation on UFAs was attributed to the homotopy
      of callosal fibers transferring visual information, while an effect of hand
      switching on CUDs was attributed mostly to spatial compatibility.

PMID- 29582108
TI  - Underestimation of large distances in active and passive locomotion.
AB  - Our ability to estimate distances, be it verbally or by locomotion, is exquisite
      at close range (action space). At distances above 100 m (vista space), verbal
      estimates continue to be quite accurate, whereas locomotor estimates have been
      found to be grossly underestimated. Until now, however, the latter have been
      performed on a treadmill, which might not translate to real-world walking. We
      investigated if the motor underestimation found on the treadmill holds up in a
      natural environment. Observers viewed pictures of objects at distances between 10
      and 245 m and were asked to reproduce these distances in a blindfolded walking
      task (using passive movement or an active production method). Active and passive
      locomotor judgments underestimated far distances above 100 m. We conclude that
      underestimation of large distances does not depend on the medium (treadmill vs.
      real-world) but rather on the sensory modality and effort involved in the task.

PMID- 29582109
TI  - Histological transformation of MALT lymphoma to plasma cell leukemia after
      rituximab-containing therapy.

PMID- 29582110
TI  - Langerhans cell histiocytosis and primary hemophagocytic lymphohistiocytosis with
      persistent clonal T-large granular lymphocyte proliferation.

PMID- 29582111
TI  - Clinical Utility of Diffusion-Weighted Imaging in Spinal Infections.
AB  - PURPOSE: Both laboratory markers and radiographic findings in the setting of
      spinal infections can be nonspecific in determining the presence or absence of
      active infection, and can lag behind both clinical symptoms and antibiotic
      response. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI)
      has been shown to be helpful in evaluating brain abscesses but has not been
      commonly used in evaluating spinal infections. We aimed to correlate findings on
      DWI of the spine to results of microbiological sampling in patients with
      suspected spinal infections. METHODS: Patients who underwent MRI with DWI for
      suspicion of spinal infections and microbiological sampling from 2002 to 2010
      were identified and reviewed retrospectively in this institutional review board
      approved study. In addition to DWI, scans included sagittal and axial T1, fast
      spin echo (FSE) T2, and post-gadolinium T1 with fat saturation. Regions of
      interest were drawn on apparent diffusion coefficient (ADC) maps in the area of
      suspected infections, and ADC values were correlated with microbiological
      sampling. RESULTS: Of 38 patients with suspected spinal infections, 29 (76%) had
      positive microbiological sampling, and 9 (24%) had negative results. The median
      ADC value was 740 * 10-6 mm2/s for patients with positive microbiological
      sampling and 1980 * 10-6 mm2/s for patients with negative microbiological
      sampling (p < 0.001). Using an ADC value of 1250 * 10-6 mm2/s or less as the cut
      off value for a positive result for spinal infection, sensitivity was 66%,
      specificity was 88%, positive predictive value was 95%, negative predictive value
      was 41% and accuracy was 70%. CONCLUSION: In patients with suspected spine
      infection, ADC values on DWI are significantly reduced in those patients with
      positive microbiological sampling compared to patients with negative
      microbiological sampling. The DWI of the spine correlates well with the presence
      or absence of spinal infection and may complement conventional magnetic resonance
      imaging (MRI).

PMID- 29582113
TI  - Mapping of new quantitative trait loci for sudden death syndrome and soybean cyst
      nematode resistance in two soybean populations.
AB  - KEY MESSAGE: Novel QTL conferring resistance to both the SDS and SCN was detected
      in two RIL populations. Dual resistant RILs could be used in breeding programs
      for developing resistant soybean cultivars. Soybean cultivars, susceptible to the
      fungus Fusarium virguliforme, which causes sudden death syndrome (SDS), and to
      the soybean cyst nematode (SCN) (Heterodera glycines), suffer yield losses valued
      over a billion dollars annually. Both pathogens may occur in the same production
      fields. Planting of cultivars genetically resistant to both pathogens is
      considered one of the most effective means to control the two pathogens. The
      objective of the study was to map quantitative trait loci (QTL) underlying SDS
      and SCN resistances. Two recombinant inbred line (RIL) populations were developed
      by crossing 'A95-684043', a high-yielding maturity group (MG) II line resistant
      to SCN, with 'LS94-3207' and 'LS98-0582' of MG IV, resistant to both F.
      virguliforme and SCN. Two hundred F7 derived recombinant inbred lines from each
      population AX19286 (A95-684043 * LS94-3207) and AX19287 (A95-684043 * LS98-0582)
      were screened for resistance to each pathogen under greenhouse conditions. Five
      hundred and eighty and 371 SNP markers were used for mapping resistance QTL in
      each population. In AX19286, one novel SCN resistance QTL was mapped to
      chromosome 8. In AX19287, one novel SDS resistance QTL was mapped to chromosome
      17 and one novel SCN resistance QTL was mapped to chromosome 11. Previously
      identified additional SDS and SCN resistance QTL were also detected in the study.
      Lines possessing superior resistance to both pathogens were also identified and
      could be used as germplasm sources for breeding SDS- and SCN-resistant soybean
      cultivars.

PMID- 29582112
TI  - Role of neurogenic inflammation in local communication in the visceral mucosa.
AB  - Intense research has focused on the involvement of the nervous system in regard
      to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera.
      Evidence supports the neural release of inflammatory factors, trophic factors,
      and neuropeptides in the initiation of inflammation. However, more recently, non
      neuronal cells including epithelia, endothelial, mast cells, and paraneurons are
      likely important participants in nervous system functions. For example, the
      urinary bladder urothelial cells are emerging as key elements in the detection
      and transmission of both physiological and nociceptive stimuli in the lower
      urinary tract. There is mounting evidence that these cells are involved in
      sensory mechanisms and can release mediators. Further, localization of afferent
      nerves next to the urothelium suggests these cells may be targets for
      transmitters released from bladder nerves and that chemicals released by
      urothelial cells may alter afferent excitability. Modifications of this type of
      communication in a number of pathological conditions can result in altered
      release of epithelial-derived mediators, which can activate local sensory nerves.
      Taken together, these and other findings highlighted in this review suggest that
      neurogenic inflammation involves complex anatomical and physiological
      interactions among a number of cell types in the bladder wall. The specific
      factors and pathways that mediate inflammatory responses in both acute and
      chronic conditions are not well understood and need to be further examined.
      Elucidation of mechanisms impacting on these pathways may provide insights into
      the pathology of various types of disorders involving the pelvic viscera.

PMID- 29582115
TI  - Osteonecrosis in sickle cell disease patients from Bahia, Brazil: a cross
      sectional study.
AB  - PURPOSE: The aim of this study was to describe the clinical features of
      osteonecrosis (ON) in sickle cell disease (SCD) patients in Bahia, a Northeast
      state with the highest prevalence of the disease in Brazil. METHODS: Between 2006
      and 2017, 283 cases of osteonecrosis in SCD patients were enrolled to analyse the
      age at diagnosis, genotype, gender, pain, distribution of the lesions and disease
      staging. MRI and radiograph were obtained at the participation. RESULTS: Of the
      283 SCD cases, 120 (42.4%) were haemoglobin SS genotype while 163 (57.6%) were SC
      genotype. Two hundred and forty-six cases were bilateral and 37 were unilateral,
      with an average age at diagnosis of 33.7 (range 10-67) years. The most frequent
      identified ON site not only was the hip (74.6%), but also affected shoulder, knee
      and ankle. Most cases presented at early stage I (172, 60.8%) disease. No
      significant differences on the features of osteonecrosis were identified between
      haemoglobin SS and haemoglobin SC cases. CONCLUSIONS: Given the relatively high
      prevalence of bilateral osteonecrosis at early stages, painful symptoms and
      rather late age at diagnosis, SCD patients should have radiological examination
      of their joints more often in order to prevent severe functional disability and
      increase patient's life quality.

PMID- 29582114
TI  - Vertical shear pelvic injury: evaluation, management, and fixation strategies.
AB  - Vertical shear pelvic ring fractures are rare and account for less than 1% of all
      fractures. Unlike severely displaced antero-posterior compression and lateral
      compression pelvic fractures, patients' mortality is lower. Nevertheless,
      patients must be managed acutely using well-defined ATLS protocols and
      institution-specific protocols for haemodynamically unstable pelvic ring
      fractures. The definitive treatment of vertical shear pelvic fractures is however
      more controversial with a paucity of literature to recommend the ideal reduction
      and fixation strategy. While the majority of injuries can be reduced and fixed in
      a closed manner, orthopaedic traumatologists should be familiar with the
      contraindications to those techniques as well as options such as tension band
      plating and lumbo pelvic fixation. Our paper reviews the acute management,
      associated injuries and definitive reduction and fixation strategies of vertical
      shear pelvic fractures. In addition, we propose a treatment algorithm for the
      selection of the most appropriate fixation technique.

PMID- 29582116
TI  - Computer-assisted surgery prevents complications during peri-acetabular
      osteotomy.
AB  - PURPOSE: The aim of study is to evaluate the accuracy of a navigation system
      during curved peri-acetabular osteotomy (CPO). METHODS: Forty-seven patients (53
      hips) with hip dysplasia were enrolled and underwent CPO with or without
      navigation during surgery. Clinical and radiographical evaluations were performed
      and compared between the navigation group and non-navigation group, post
      operatively. RESULTS: The clinical outcomes were not significantly different
      between the navigation and non-navigation groups. Furthermore, post-operative
      reorientation of the acetabular fragment was similar between the navigation and
      non-navigation groups. However, the discrepancy between the pre-operative
      planning line and post-operative osteotomy line was significantly improved in the
      navigation group compared with that in the non-navigation group (p < 0.05).
      Further, the complication rate was significantly improved in the navigation group
      (p < 0.001). CONCLUSION: The accuracy of the osteotomy's position was
      significantly improved by using the navigation. Therefore, the use of navigation
      during peri-acetabular osteotomy can avoid complications.

PMID- 29582117
TI  - Double calcaneal osteotomy with minimally invasive surgery for the treatment of
      severe flexible flatfeet.
AB  - BACKGROUND: Severe flexible flatfoot deformity in children and adolescents is a
      complex problem. Calcaneal lengthening remains the gold standard for surgical
      correction at this institution. However, in a minority of patients, inadequate
      correction of valgus is noted at surgery and a further calcaneal shift osteotomy
      is done. METHODS: We have conducted a retrospective review of ten patients who
      received 15 combined minimally invasive calcaneal shift and calcaneal lengthening
      osteotomies, which were all performed by the senior author. All patients had
      failed conservative treatment. We describe our technique for double calcaneal
      osteotomy combining minimally invasive surgery (MIS) for the medial calcaneal
      shift with traditional open calcaneal lengthening osteotomy for treating children
      and adolescents with severe flexible flatfoot deformity. RESULTS: The average
      shift achieved was 8.07 mm. The average improvement in Meary's angle was 14.99
      degrees . All of them had radiological and clinical union at 12 weeks. None of
      the patients developed sural nerve injury, wound breakdown, or infection of the
      MIS incision. CONCLUSION: In double calcaneal osteotomies, the MIS calcaneal
      medial shift technique can be used safely with potentially lower risks of wound
      complications and sufficient medial shift, compared to conventional open
      extensive surgery. IMPLICATIONS: MIS calcaneal shift osteotomy has an advantage
      over open conventional open technique in cases where the skin is under tension
      like in combined calcaneal lengthening osteotomy. With experience, the procedure
      can be faster than an open procedure.

PMID- 29582118
TI  - Reverse total shoulder arthroplasty using helical blade to optimize glenoid
      fixation and bone preservation: preliminary results in thirty five patients with
      minimum two year follow-up.
AB  - PURPOSE: Glenoid loosening is a common cause of reverse total shoulder
      arthroplasty (RTSA) failure, and grafting of the glenoid is often required for
      revision due to bone loss due to the central peg in most glenoid baseplates.
      Helical blades have been used in the hip to optimize bone fixation in proximal
      femoral fracture. This study presents the initial results of specifically
      designed helical blade in the shoulder to optimize glenoid bone fixation and
      preservation as part of RTSA. METHODS: Thirty-five patients underwent RTSA with
      glenoid helical blade fixation. An uncemented glenoid baseplate was used with a
      central helical blade partially coated with hydroxyapatite and two or three
      screws. Outcome analysis was performed pre-operatively and at two years. RESULTS:
      All patients were satisfied with the results and significant improvement was
      observed in functional outcome scores between baseline and final follow-up. There
      was a single intra-operative undisplaced glenoid fracture which did not
      compromise the baseplate fixation. There was no radiographic evidence of
      loosening or radiolucencies around the helical blade. CONCLUSIONS: The helical
      blade provides a satisfactory primary fixation. Because of its length (21 mm),
      care should be taken in cases of pre-existing bone loss or sclerotic bone to
      avoid glenoid fracture or anterior cortical perforation. Helical blade has the
      potential to facilitate glenoid implant revision by preserving the glenoid bone
      stock.

PMID- 29582119
TI  - Molecularly imprinted polymers fabricated via Pickering emulsions stabilized
      solely by food-grade casein colloidal nanoparticles for selective protein
      recognition.
AB  - Novel molecularly imprinted polymers (MIPs) based on denatured casein
      nanoparticle (DCP)-stabilized Pickering emulsions were developed for the first
      time. Casein, a phosphoprotein, is the main protein in milk. In this work, DCPs
      were solely used as Pickering-type interfacial emulsifiers for fabrication of
      MIPs for the selective recognition of proteins for the first time. DCPs were
      prepared by acidification and heat denaturation (at 80  degrees C) of casein.
      Their dispersions have satisfactory colloidal stability over a wide pH range. The
      DCPs acted as natural, food-grade, and edible interfacial emulsifiers, and
      adsorbed at the oil-water interface to form Pickering emulsions. After the
      polymerization of monomers, the template protein was removed by elution. During
      the elution, the interfacial DCPs were also removed, allowing more imprinted
      cavities to become exposed. The interfacial imprinting technology causes nearly
      all the imprinted sites to locate on the surface of the polymeric material.
      Therefore, the MIPs obtained exhibit fast rebinding and excellent specific
      recognition ability toward the analytes. Overall, this work provides a promising
      method for designing and fabricating natural-protein-based structured emulsions
      to prepare MIPs and thus offers new insight into protein separation and
      purification. Graphical Abstract Pickering emulsions stabilized by denatured
      casein particles.

PMID- 29582121
TI  - Naked eye detection of infertility based on sperm protamine-induced aggregation
      of heparin gold nanoparticles.
AB  - The development of an easy to use, one-pot, environmentally friendly, non
      invasive and label-free colorimetric probe for the determination of semen
      protamines, the biochemical marker of male fertility, using heparin gold
      nanoparticles (HAuNPs) is presented. The affinity of HAuNPs for protamines was
      due to the electrostatic interactions between polycationic protamine and
      polyanionic heparin. The binding of HAuNPs to protamine was characterized by
      variation in the plasmon absorption spectra followed by a visibly observable
      colour change of the solution from red to blue. We observed a red shift in the
      plasmon peak and the method exhibited linearity in the range of 10-70 ng/mL with
      a detection limit of 5 ng/mL, which is much lower than that reported for
      colorimetric sensors of protamine. The colour change and the variation in the
      absorbance of HAuNPs were highly specific for protamines in the presence of
      different interfering compounds and the method was successfully applied for
      determining protamine in real samples of semen and serum. Rather than a
      quantitative estimation, it seems that the method provides a quick screening
      between a large array of positive and negative samples and, moreover, it
      maintains the privacy of the user. The method appears to be simple and would be
      very useful in third-world countries where high-tech diagnostic aids are
      inaccessible to the majority of the population. Graphical Abstract Heparin gold
      nanoparticles aided visual detection of infertility.

PMID- 29582122
TI  - Comprehensive 2D gas chromatography-time-of-flight mass spectrometry with 2D
      retention indices for analysis of volatile compounds in frankincense (Boswellia
      papyrifera).
AB  - Frankincense gum resin secreted from Boswellia papyrifera was analysed by
      comprehensive 2D gas chromatography hyphenated with accurate mass time-of-flight
      mass spectrometry (GC*GC-accTOFMS). Direct multiple injection experiments with
      stepwise isothermal temperature programming were then performed to construct
      isovolatility curves for reference alkane series in GC*GC. This provides access
      to calculation of second dimensional retention indices (2I). More than 500 peaks
      were detected and 220 compounds mainly comprising monoterpenes, sesquiterpenes,
      diterpenes and oxygenated forms of these compounds were identified according to
      their 1I, 2I and accurate mass data. The study demonstrates the capability of
      GC*GC-accTOFMS with retention data on two separate column phases, as an approach
      for improved component identification. A greater number of identified and/or
      tentatively identified terpenoids in this traditional Chinese medicine allow for
      a more comprehensive coverage of the volatile composition of frankincense.

PMID- 29582120
TI  - Consumer-friendly food allergen detection: moving towards smartphone-based
      immunoassays.
AB  - In this critical review, we provide a comprehensive overview of immunochemical
      food allergen assays and detectors in the context of their user-friendliness,
      through their connection to smartphones. Smartphone-based analysis is centered
      around citizen science, putting analysis into the hands of the consumer. Food
      allergies represent a significant worldwide health concern and consumers should
      be able to analyze their foods, whenever and wherever they are, for allergen
      presence. Owing to the need for a scientific background, traditional laboratory
      based detection methods are generally unsuitable for the consumer. Therefore, it
      is important to develop simple, safe, and rapid assays that can be linked with
      smartphones as detectors to improve user accessibility. Smartphones make
      excellent detection systems because of their cameras, embedded flash functions,
      portability, connectivity, and affordability. Therefore, this review has
      summarized traditional laboratory-based methods for food allergen detection such
      as enzyme-linked-immunosorbent assay, flow cytometry, and surface plasmon
      resonance, and the potential to modernize these methods by interfacing them with
      a smartphone readout system, based on the aforementioned smartphone
      characteristics. This is the first review focusing on smartphone-based food
      allergen detection methods designed with the intention of being consumer
      friendly. Graphical abstract A smartphone-based food allergen detection system in
      three easy steps (1) sample preparation, (2) allergen detection on a smartphone
      using antibodies, which then transmits the data wirelessly, (3) analytical
      results sent straight to smartphone.

PMID- 29582123
TI  - Increased incidence of abnormally located ovary in patients with Mayer-Rokitansky
      Kuster-Hauser syndrome: a retrospective analysis with magnetic resonance imaging.
AB  - PURPOSE: To explore the incidence of abnormally located ovary in patients with
      Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome as compared to a control group
      with magnetic resonance imaging. METHODS: Pelvic MR images of 83 MRKH patients
      and 60 age-matched normal females were retrospectively reviewed by two
      experienced gynecological radiologists in consensus. Characteristics including
      location of ovary, ovarian volume, and follicle counts were assessed. The
      incidence of abnormally located ovary was compared between MRKH patients and
      controls. The ovarian size and follicle counts were compared among three groups:
      abnormally located ovaries in MRKH patients, eutopic ovaries in MRKH patients,
      and normal controls. RESULTS: In total, 166 ovaries of 83 MRKH patients and 120
      ovaries of 60 control females were evaluated. Thirty-seven ovaries of 23 MRKH
      patients (28%, 23/83) were abnormally located, whereas 3 ovaries of three control
      females (5%, 3/60) were located in abnormal positions (P < 0.001). The mean
      volume was 9.2 +/- 6.3 mL of the abnormally located ovaries in MRKH patients, 7.8
      +/- 4.0 mL of the eutopic ovaries in MRKH patients, and 8.9 +/- 4.8 mL in control
      females (P > 0.05). No obvious differences were observed with regard to follicle
      counts among the three groups. CONCLUSION: Incidence of abnormally located ovary
      was significantly increased in patients with MRKH syndrome. Such knowledge is
      important for infertility treatment, evaluation of pelvic pain, and surgical
      planning for MRKH patients.

PMID- 29582124
TI  - Relative diagnostic utility of radiologist-recommended abdominal ultrasound
      following emergency department abdominal and pelvic computed tomography.
AB  - PURPOSE: To retrospectively assess the relative diagnostic utility of radiologist
      recommended ultrasound (US) following emergency department (ED) abdominal and
      pelvic computed tomography (CT) in patients with non-traumatic abdominal and/or
      pelvic pain. METHODS: Blinded to clinical outcomes, two radiology residents and
      an attending radiologist reviewed radiology reports and relevant medical records
      for all adult patients from EDs at two academic medical centers from one
      institution over a 3-year time period, who underwent abdominal/pelvic US within
      72 h of an initial IV contrast-enhanced abdominal and pelvic CT for non-traumatic
      abdominal and/or pelvic pain. Incremental diagnostic utility of subsequent US was
      deemed present when (1) US findings were discordant with those at CT, or (2)
      findings were concordant, but US yielded additional relevant diagnostic
      information. Diagnostic utility was stratified by whether examinations were
      radiologist-recommended or independently ordered by treating physicians. RESULTS:
      319 encounters satisfied the inclusion criteria, including 194 female patients
      (18-98 years of age, mean of 59.8 years) and 125 male patients (20-90 years of
      age, mean of 63.2 years). 7 (2.2%) subsequent US examinations were discordant
      with the initial CT, 100 (31.3%) were concordant but provided relevant additional
      information, and 212 (66.5%) were concordant without providing additional
      information, for an overall diagnostic utility of 33.5%. Of subsequent
      radiologist-recommended US examinations, 70.0% (63/90) yielded incremental
      diagnostic utility vs. 19.2% (44/229) ordered independently by treating
      physicians (OR 3.65; 95% CI 2.31-5.75). For those encounters in which US provided
      incremental diagnostic utility, the most commonly assessed anatomical areas were
      the biliary system and the female adnexal region. CONCLUSION: In ED patients with
      non-traumatic abdominal and/or pelvic pain undergoing abdominal and pelvic CT,
      follow-up US examinations recommended by radiologists are more likely to provide
      incremental diagnostic utility than those independently ordered by their treating
      physicians. In order to optimize the value of advanced imaging, radiologists
      should assume greater roles in team-based utilization management.

PMID- 29582125
TI  - Does the Site of the Primary Affect Outcomes When Ablating Colorectal Liver
      Metastases with Radiofrequency Ablation?
AB  - PURPOSE: To determine whether primary tumor side was a predictor of
      radiofrequency ablation (RFA) outcome in colorectal liver metastases (CRLM).
      MATERIALS AND METHODS: The institutional review board approved this retrospective
      study. Written informed consent was obtained from all patients. From January 2007
      to December 2013, 102 patients underwent RFA of metachronous CRLM were enrolled
      in this study with propensity score matching method. Recurrence rate (RR) and
      overall survival (OS) were analyzed between two patients cohorts with primary
      left-side colorectal cancer (LSCRC) or primary right-side colon cancer (RSCC).
      RESULTS: The total RR was 59.8% in all patients. Patients in LSCRC cohort had
      lower RR and non-local recurrence (NLR) rate than those in RSCC patients' cohort
      (49.0 vs 70.6%, p = 0.026 and 21.6 vs 41.2%, p = 0.033). Five-year OS was 14 and
      30% for RSCC and LSCRC, respectively. There was a significant difference between
      two cohorts in median OS (29.4 vs 40.3 months for RSCC and LSCRC, respectively, p
      = 0.042). Univariate analysis showed that primary tumor side, the number of liver
      metastases, tumor size, carcinoembryonic antigen level, differentiation, TNM
      stage, active chemotherapy and RFA boundary were significant in predicting OS.
      When these variables were subsequently entered in a multivariate model, RSCC (p <
      0.001; hazard ratio [HR], 6.2) and tumor size (> 3 cm) (p = 0.006; HR, 3.9) were
      significant. CONCLUSION: LSCRC and tumor size (<= 3 cm) are independent
      predictors of RFA in CRLM and yield the better oncologic outcomes.

PMID- 29582126
TI  - Endovascular Treatment of Haemodialysis Arteriovenous Fistula with Drug-Coated
      Balloon Angioplasty: A Single-Centre Study.
AB  - PURPOSE: To evaluate the effect of percutaneous transluminal angioplasty (PTA) on
      haemodialysis fistulas utilising drug-coated balloons with plain balloon vessel
      preparation (DCB). MATERIALS AND METHODS: In the study group, 31 patients (16
      men; mean age 62.8 +/- 17.2 years) with failing arteriovenous fistulas were
      treated, with DCB, and compared with a control group (31 patients; 15 men; mean
      age 67.0 +/- 8.44 years), in which only plain balloon PTA was performed. All
      stenoses were dilated with regular PTA balloons. After achieving haemodynamic
      success (< 30% residual stenosis), drug-coated balloons were used for drug
      administration in the study group. The follow-up intervals were 6, 12 and 24
      months. Target lesion primary patency, primary assisted patency and secondary
      patency were compared. The statistical significance was set at 0.05. RESULTS:
      Target lesion primary patency was compared in both groups and was significantly
      higher in the study group (DCB) at 6 months (90.3 vs. 61.3%; p = 0.016), 12
      months (77.4 vs. 29%; p = 0.0004) as well as 24 months (45.2 vs. 16.1%; p =
      0.026). Kaplan-Meier survival curves also showed a significant difference for
      target lesion primary patency (534.2 vs. 315.7 days; p = 0.0004). There were no
      significant differences in target lesion primary assisted patency and in
      secondary patency. However, only 38.7% of patients in the study group were
      treated twice or more versus 80.6% in the control group (p = 0.002). CONCLUSION:
      DCB increases target lesion primary patency during the first 24 months and
      decreases the rate of reinterventions.

PMID- 29582127
TI  - Prostatic Artery Embolization (PAE) for Benign Prostatic Hyperplasia (BPH) with
      Haematuria in the Absence of an Upper Urinary Tract Pathology.
AB  - PURPOSE: To assess the effectiveness of prostate artery embolization (PAE) in the
      control of haematuria and in patients with benign prostatic hyperplasia (BPH) and
      normal upper urinary tracts. SUBJECTS/PATIENTS: Twelve consecutive patients with
      haematuria were included in the prospective study. All patients had prior imaging
      and cystoscopy to exclude other causes of haematuria. Patients prostate arteries
      were embolized with particles (200-500 MUm), and they were followed up at 3, 12
      and 18 months following the procedure. QOL questionnaires, IPSS, IIEF and
      clinical review were all employed to assess the success of the treatment. To
      allow useful comparison, patients were age- and prostate volume-matched and
      compared to patients treated with PAE for BPH without haematuria. RESULTS: All
      12/12 cases were technically successful with bilateral PAE being performed. All
      cases of haematuria resolved by the 3-month follow-up (100%). There was one case
      of recurrence during the 12-month follow-up (overall clinical success at 18
      months 92%). This was due to over anticoagulation and ceased once corrected.
      There was a reduction in lower urinary tract symptoms noted by improvements in
      QOL indices, IPSS and IIEF. There was continued success even if the patient was
      subsequently anticoagulated. There was no associated sexual dysfunction. There
      was more prostatic arterial branching and volume of embolic required to achieve
      stasis in BPH and haematuria than in BPH alone (p < 0.05). CONCLUSION: PAE is a
      very useful technique for controlling the quite debilitating condition of
      haematuria in patients with visible haematuria of prostatic origin. Controlling
      haematuria and BPH allows a significant improvement in QOL.

PMID- 29582128
TI  - Safety and Efficacy of Percutaneous Thermal Ablation of Juxta-Cardiac Hepatic
      Tumours.
AB  - INTRODUCTION: To evaluate the safety and efficacy of percutaneous thermal
      ablation of liver tumours in a juxta-cardiac (JC) location. MATERIALS AND
      METHODS: From January 2010 to December 2014, out of 274 cases of hepatic
      ablation, 33 consecutive patients who received thermal ablation (radiofrequency
      or microwave) to left hepatic lobe tumours were included in this study. Patients
      were divided into two groups: JC or non-juxta-cardiac (NJC) (tumour margin <= 10
      mm or > 10 mm from the cardiac border, respectively). Imaging follow-up was
      performed at 6-week and 3-monthly intervals. Technical success, 30-day
      complications and local tumour control/recurrence were recorded. Statistical
      analysis was performed with t test and Fisher's test. Univariate and multivariate
      survival analyses were performed using Cox regression. RESULTS: Patients
      comprised of 23 men and 10 women (mean age 67.0 years). Mean tumour size was 2.2
      +/- 0.9 cm (28 hepatocellular carcinoma and 5 metastases). Mean follow-up time
      was 21.2 months (range 2-72 months). There were no differences between the JC and
      NJC groups in the rates of complete ablation (86.7 vs 83.3% P = 1.0), tumour
      recurrence (20.0 vs 22.2%, P = 0.95) or complication rates (6.7 vs 11.1% P =
      1.0). Metastatic lesions were associated with a higher rate of recurrent disease
      (hazard ratio 3.86, 95% CI 1.0-14.8%, P = 0.05). DISCUSSION: Percutaneous thermal
      ablation of JC tumours has similar rates of local tumour control and safety
      profile when compared to tumours in a NJC location. Tumours in a JC location
      should not be considered a contraindication for thermal ablation.

PMID- 29582129
TI  - Evaluating the Feasibility of Isolated Pancreatic Perfusion for Chemotherapy
      Using Computed Tomography: An Experimental Study in Pig Models.
AB  - PURPOSE: Percutaneous isolated pancreatic perfusion (PIPP) is performed along
      with interventional radiology techniques to obtain high drug concentration by
      occluding the arterial inlet and venous outlet of the pancreas. The experimental
      study aimed to evaluate the contrast distribution in PIPP under different flow
      rates with or without anterior mesenteric artery (AMA) occlusion. MATERIALS AND
      METHODS: This study was approved by a local animal experiment ethics committee.
      Nine pigs were divided into Groups 1, 2, and 3, by infusion rates of 12, 24, and
      36 mL/min. Groups 4 and 5 (3 pigs each) and Group 6 (2 pigs) underwent PIPP at
      the same respective infusion rates with and without AMA occlusion. Computed
      tomography (CT) arteriography was performed during PIPP with nonionic contrast
      media. The enhanced volume was calculated by adding the enhanced area in each
      slice using 1.25-mm axial images. The percent enhanced volume to the whole
      pancreas (%eV) was used to simulate drug distribution; the result was compared
      among groups. RESULTS: Without AMA occlusion, a larger %eV was obtained with high
      infusion rates (P = 0.039). The median %eV in Groups 1, 2, and 3 were 57.7, 74.2,
      and 90.5%, respectively. With AMA occlusion, CT demonstrated duodenal enhancement
      at an infusion rate of 36 mL/min, and the median %eV in Groups 4, 5, and 6 were
      92.8, 95.4, and 98.5%, respectively. A significantly larger %eV was obtained
      after AMA occlusion (P = 0.031). CONCLUSION: A higher infusion rate or AMA
      occlusion increases the enhanced volume in PIPP in pig models. LEVEL OF EVIDENCE:
      No level of evidence.

PMID- 29582130
TI  - Conventional radiography in juvenile idiopathic arthritis: Joint recommendations
      from the French societies for rheumatology, radiology and paediatric
      rheumatology.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) can cause structural damage.
      However, data on conventional radiography (CR) in JIA are scant. OBJECTIVE: To
      provide pragmatic guidelines on CR in each non-systemic JIA subtype. METHODS: A
      multidisciplinary task force of 16 French experts (rheumatologists,
      paediatricians, radiologists and one patient representative) formulated research
      questions on CR assessments in each non-systemic JIA subtype. A systematic
      literature review was conducted to identify studies providing detailed
      information on structural joint damage. Recommendations, based on the evidence
      found, were evaluated using two Delphi rounds and a review by an independent
      committee. RESULTS: 74 original articles were included. The task force developed
      four principles and 31 recommendations with grades ranging from B to D. The
      experts felt strongly that patients should be selected for CR based on the risk
      of structural damage, with routine CR of the hands and feet in rheumatoid factor
      positive polyarticular JIA but not in oligoarticular non-extensive JIA.
      CONCLUSION: These first pragmatic recommendations on CR in JIA rely chiefly on
      expert opinion, given the dearth of scientific evidence. CR deserves to be viewed
      as a valuable tool in many situations in patients with JIA. KEY POINTS: * CR is a
      valuable imaging technique in selected indications. * CR is routinely recommended
      for peripheral joints, when damage risk is high. * CR is recommended according to
      the damage risk, depending on JIA subtype. * CR is not the first-line technique
      for imaging of the axial skeleton.

PMID- 29582131
TI  - The role of imaging in the management of necrotising enterocolitis: a
      multispecialist survey and a review of the literature.
AB  - OBJECTIVES: To investigate current practices and perceptions of imaging in
      necrotising enterocolitis (NEC) according to involved specialists, put them in
      the context of current literature, and identify needs for further investigation.
      METHODS: Two hundred two neonatologists, paediatric surgeons, and radiologists
      answered a web-based questionnaire about imaging in NEC at their hospitals. The
      results were descriptively analysed, using proportion estimates with 95%
      confidence intervals. RESULTS: There was over 90% agreement on the value of
      imaging for confirmation of the diagnosis, surveillance, and guidance in
      decisions on surgery as well as on abdominal radiography as the first-choice
      modality and the most important radiographic signs. More variation was observed
      regarding some indications for surgery and the use of some ultrasonographic
      signs. Fifty-eight per cent stated that ultrasound was used for NEC at their
      hospital. Examination frequency, often once daily or more but with considerable
      variations, and projections used in AR were usually decided individually rather
      than according to fixed schedules. Predicting the need of surgery was regarded
      more important than formal staging. CONCLUSION: Despite great agreement on the
      purposes of imaging in NEC and the most important radiographic signs of the
      disease, there was considerable diversity in routines, especially regarding
      examination frequency and the use of ultrasound. Apart from continuing validation
      of ultrasound, important objectives for future studies include definition of the
      supplementary roles of both imaging modalities in relation to other diagnostic
      parameters and evaluation of various imaging routines in relation to timing of
      surgery, complications, and mortality rate. KEY POINTS: * Imaging is an
      indispensable tool in the management of necrotising enterocolitis * Predicting
      the need of surgery is regarded more important than formal staging * There is
      great consensus on important signs of NEC on abdominal radiography * There is
      more uncertainty regarding the role of ultrasound * Individualised management is
      preferred over standardised diagnostic algorithms.

PMID- 29582132
TI  - Association of Plasma Irisin with Bone Mineral Density in a Large Chinese
      Population Using an Extreme Sampling Design.
AB  - Irisin, a myokine produced by skeletal muscle in response to physical exercise,
      promotes trans-differentiation of white adipose tissue into brown adipose tissue.
      Recent evidences suggested that irisin also plays an important role in the
      control of bone metabolism. This study aimed to ascertain the relationship
      between plasma irisin and bone mineral density (BMD) in Chinese population by
      adoption of an extreme sampling method. Based on a large and screened Chinese
      elderly population (N = 6308), two subgroups with extremely high and low hip BMD
      were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N
      = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and beta-CTx
      were measured using commercially available ELISA kits. Other metabolic parameters
      (e.g., blood glucose, total cholesterol and triglycerides) were collected.
      Student's t test and Spearman correlation analyses were conducted in SPSS.
      Significant difference was discovered for plasma irisin between females and age
      matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin
      levels were significantly higher in high BMD subjects than in low BMD subjects,
      which was observed in both discovery (P = 0.012) and validation samples (P =
      0.022). However, such observation was limited to males only. Further correlation
      analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P
      = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were
      associated with hip BMD in Chinese elderly men. This study represented the first
      effort of investigating the relationship of plasma irisin and BMD in elderly
      population. The positive correlation between plasma irisin and BMD hints
      intrinsic communication between muscle and bone.

PMID- 29582133
TI  - Marrow Adipose Tissue in Older Men: Association with Visceral and Subcutaneous
      Fat, Bone Volume, Metabolism, and Inflammation.
AB  - Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic
      profiles and varying associations with aging, bone density, and fracture risk.
      Using a non-invasive imaging methodology, we aimed to investigate the
      associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone
      remodeling markers, insulin resistance, and circulating inflammatory mediators in
      a population of older men. In this cross-sectional study, 96 healthy men (mean
      age 67 +/- 5.5) were assessed for anthropometric parameters, body composition,
      serum biochemistry, and inflammatory panel. Using single-energy computed
      tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level
      of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision),
      which enables specific tissue demarcation applying previously reported Hounsfield
      unit thresholds. MAT volume was similar in all anatomical sites and independent
      of BMI. In all femoral regions of interest (ROIs) there was a strong negative
      association between bone and MAT volumes (r = - 0.840 to - 0.972, p < 0.001),
      with location-dependent variations in the lumbar spine. Unlike VAT and SAT, no
      associations between MAT and serum glucose, inflammatory markers or insulin
      resistance indicators were found. Bone decline occurred without red marrow
      expansion; thus lost bone was mainly (if not exclusively) replaced by MAT. In
      conclusion, strong inverse correlations between MAT and bone mass, which have
      been previously observed in women, were also confirmed in older men. However, MAT
      volume in all ROIs was interrelated and unlike women, mainly independent of VAT
      or SAT. The lack of strong association between MAT vs VAT/SAT, and its discordant
      associations with metabolic and inflammatory mediators provide further evidence
      on MAT's distinct attributes in older men.

PMID- 29582135
TI  - Forensic molecular genetic diversity analysis of Chinese Hui ethnic group based
      on a novel STR panel.
AB  - In present study, the genetic polymorphisms of 22 autosomal short tandem repeat
      (STR) loci were analyzed in 496 unrelated Chinese Xinjiang Hui individuals. These
      autosomal STR loci were multiplex amplified and genotyped based on a novel STR
      panel. There were 246 observed alleles with the allele frequencies ranging from
      0.0010 to 0.3609. All polymorphic information content values were higher than
      0.7. The combined power of discrimination and the combined probability of
      exclusion were 0.999999999999999999999999999426766 and 0.999999999860491,
      respectively. Based on analysis of molecular variance method, genetic
      differentiation analysis between the Xinjiang Hui and other reported groups were
      conducted at these 22 loci. The results indicated that there were no significant
      differences in statistics between Hui group and Northern Han group (including Han
      groups from Hebei, Henan, Shaanxi provinces), and significant deviations with
      Southern Han group (including those from Guangdong, Guangxi provinces) at 7 loci,
      and Uygur group at 10 loci. To sum up, these 22 autosomal STR loci were high
      genetic polymorphic in Xinjiang Hui group.

PMID- 29582134
TI  - Effects of the recombinant crustacean hyperglycemic hormones rCHH-B1 and rCHH-B2
      on the osmo-ionic regulation of the shrimp Litopenaeus vannamei exposed to acute
      salinity stress.
AB  - The Pacific white shrimp Litopenaeus vannamei is a euryhaline organism that copes
      with salinity fluctuations in the environment; therefore, its osmotic and ionic
      regulation abilities are vital. Osmoregulation may be controlled by the
      crustacean hyperglycemic hormone (CHH), a neuropeptide mainly expressed in the
      eyestalks. In L. vannamei, CHH-B1 and CHH-B2 are CHH isoforms isolated from the
      eyestalks whose expression is influenced by environmental salinity. It has been
      suggested that they are involved in the response to salinity stress. To clarify
      this, we investigated the effect of the recombinant peptides, rCHH-B1 and rCHH
      B2, on the osmo-ionic regulation of shrimp acutely exposed to different salinity
      conditions (8, 26 and 450/00). Both rCHHs promoted differential effects on the
      osmoregulatory capacity (OC) and the ionoregulatory capacity (IC) for hemolymph
      Na+ and Cl- during iso-osmotic (260/00) and hyper-osmotic (450/00) transfers.
      These changes were linked to the changes observed in Na+/K+ ATPase and carbonic
      anhydrase gene expression in gills, especially under high salinity conditions,
      suggesting that the hormones may regulate the expression of these genes. Glucose
      and protein levels measured during acute salinity transfer suggest their roles as
      sources of metabolic energy for osmotic regulation or as organic osmolytes. These
      results taken together suggest that both the CHH-B1 and CHH-B2 peptides are
      important regulators of the physiological response of L. vannamei to acute
      salinity fluctuations.

PMID- 29582136
TI  - Unexplained cardiac arrest: a tale of conflicting interpretations of KCNQ1
      genetic test results.
AB  - OBJECTIVE: Unexplained cardiac arrest (UCA) is often the first manifestation of
      an inherited arrhythmogenic disease. Genetic testing in UCA is challenging due to
      the complexities of variant interpretation in the absence of supporting cardiac
      phenotype. We aimed to investigate if a KCNQ1 variant [p.(Pro64_Pro70del)],
      previously reported as pathogenic, contributes to the long-QT syndrome phenotype,
      co-segregates with disease or affects KCNQ1 function in vitro. METHODS: DNA was
      extracted from peripheral blood of a 22-year-old male after resuscitation from
      UCA. Targeted exome sequencing was performed using the TruSight-One Sequencing
      Panel (Illumina). Variants in 190 clinically relevant cardiac genes with minor
      allele frequency < 1% were analyzed according to the guidelines of the American
      College of Medical Genetics. Functional characterization was performed using site
      directed mutagenesis, expression in Xenopus laevis oocytes using the two
      electrode voltage-clamp technique. RESULTS: The 12-lead ECG, transthoracic
      echocardiography and coronary angiography after resuscitation showed no specific
      abnormalities. Two variants were identified: c.190_210del in-frame deletion in
      KCNQ1 (p.Pro64_Pro70del), reported previously as pathogenic and c.2431C > A in
      PKP2 (p.Arg811Ser), classified as likely benign. Two asymptomatic family members
      with no evident phenotype hosted the KCNQ1 variant. Functional studies showed
      that the wild-type and mutant channels have no significant differences in current
      levels, conductance-voltage relationships, as well as activation and deactivation
      kinetics, in the absence and presence of the auxiliary subunit KCNE1.
      CONCLUSIONS: Based on our data and previous reports, available evidence is
      insufficient to consider the variant KCNQ1:c.190_210del as pathogenic. Our
      findings call for cautious interpretation of genetic tests in UCA in the absence
      of a clinical phenotype.

PMID- 29582137
TI  - Diversity and common themes in the organization of ocelli in Hymenoptera, Odonata
      and Diptera.
AB  - We show in a comparative analysis that distinct retinal specializations in insect
      ocelli are much more common than previously realized and that the rhabdom
      organization of ocellar photoreceptors is extremely diverse. Hymenoptera, Odonata
      and Diptera show prominent equatorial fovea-like indentations of the ocellar
      retinae, where distal receptor endings are furthest removed from the lens surface
      and receptor densities are highest. In contrast, rhabdomere arrangements are very
      diverse across insect groups: in Hymenoptera, with some exceptions, pairs of
      ocellar retinular cells form sheet-like rhabdoms that form elongated rectangular
      shapes in cross-section, with highly aligned microvilli directions perpendicular
      to the long axis of cross-sections. This arrangement makes most ocellar retinular
      cells in Hymenoptera sensitive to the direction of polarized light. In
      dragonflies, triplets of retinular cells form a y-shaped fused rhabdom with
      microvilli directions oriented at 60 degrees  to each other. In Dipteran ocellar
      retinular cells microvilli directions are randomised, which destroys polarization
      sensitivity. We suggest that the differences in ocellar organization between
      insect groups may reflect the different head attitude control systems that have
      evolved in these insect groups, but possibly also differences in the mode of
      locomotion and in the need for celestial compass information.

PMID- 29582138
TI  - A lake classification concept for a more accurate global estimate of the
      dissolved inorganic carbon export from terrestrial ecosystems to inland waters.
AB  - The magnitude of lateral dissolved inorganic carbon (DIC) export from terrestrial
      ecosystems to inland waters strongly influences the estimate of the global
      terrestrial carbon dioxide (CO2) sink. At present, no reliable number of this
      export is available, and the few studies estimating the lateral DIC export assume
      that all lakes on Earth function similarly. However, lakes can function along a
      continuum from passive carbon transporters (passive open channels) to highly
      active carbon transformers with efficient in-lake CO2 production and loss. We
      developed and applied a conceptual model to demonstrate how the assumed function
      of lakes in carbon cycling can affect calculations of the global lateral DIC
      export from terrestrial ecosystems to inland waters. Using global data on in-lake
      CO2 production by mineralization as well as CO2 loss by emission, primary
      production, and carbonate precipitation in lakes, we estimated that the global
      lateral DIC export can lie within the range of [Formula: see text] to [Formula:
      see text] Pg C yr-1 depending on the assumed function of lakes. Thus, the
      considered lake function has a large effect on the calculated lateral DIC export
      from terrestrial ecosystems to inland waters. We conclude that more robust
      estimates of CO2 sinks and sources will require the classification of lakes into
      their predominant function. This functional lake classification concept becomes
      particularly important for the estimation of future CO2 sinks and sources, since
      in-lake carbon transformation is predicted to be altered with climate change.

PMID- 29582139
TI  - Live cell analyses of synaptonemal complex dynamics and chromosome movements in
      cultured mouse testis tubules and embryonic ovaries.
AB  - During mammalian meiotic prophase, homologous chromosomes connect through the
      formation of the synaptonemal complex (SC). SYCP3 is a component of the lateral
      elements of the SC. We have generated transgenic mice expressing N- or C-terminal
      fluorescent-tagged SYCP3 (mCherry-SYCP3 (CSYCP) and SYCP3-mCherry (SYCPC)) to
      study SC dynamics and chromosome movements in vivo. Neither transgene rescued
      meiotic aberrations in Sycp3 knockouts, but CSYCP could form short axial element
      like structures in the absence of endogenous SYCP3. On the wild-type background,
      both fusion proteins localized to the axes of the SC together with endogenous
      SYCP3, albeit with delayed initiation (from pachytene) in spermatocytes. Around
      40% of CSYCP and SYCPC that accumulated on the SC was rapidly exchanging with
      other tagged proteins, as analyzed by fluorescent recovery after photobleaching
      (FRAP) assay. We used the CSYCP transgenic mice for further live cell analyses
      and observed synchronized bouquet configurations in living cysts of two or three
      zygotene oocyte nuclei expressing CSYCP, which presented cycles of telomere
      clustering and dissolution. Rapid chromosome movements were observed in both
      zygotene oocytes and pachytene spermatocytes, but rotational movements of the
      nucleus were more clear in oocytes. In diplotene spermatocytes, desynapsis was
      found to proceed in a discontinuous manner, whereby even brief chromosome re
      association events were observed. Thus, this live imaging approach can be used to
      follow changes in the dynamic behavior of the nucleus and chromatin, in normal
      mice and different infertile mouse models.

PMID- 29582140
TI  - Parental care compromises feeding in the pumpkinseed (Lepomis gibbosus).
AB  - Providing parental care is potentially costly. Costs can arise through elevated
      energy expenditure or from an increased risk of mortality. A cost of parental
      care can also occur because a parent is compromised in their ability to forage.
      We used pumpkinseed Lepomis gibbosus, a fish with an alternative male mating
      strategy, to test whether parental males differed in their feeding in comparison
      with females and cuckolder males. To address this question, we examined the
      stomach contents of female, cuckolder male, and parental male pumpkinseed during
      the breeding season over an entire diel cycle. We showed that parental males had
      a lower total weight of food in their stomachs in comparison with females, while
      cuckolder males did not. Parental males also had a lower weight and number of
      chironomids in their stomachs. The temporal pattern of feeding of parental males
      diverged from that of females, and they had a lower probability of pupal
      chironomids in their stomachs, which implies spatial segregation in foraging.
      Parental males had a greater probability of conspecific eggs in their stomachs
      than females, while the probability of egg cannibalism did not differ between
      cuckolder males and females. Overall, these finding meet predictions in
      accordance with an assumption that parental care and territoriality can
      compromise feeding.

PMID- 29582141
TI  - Diagnosis of glenoid labral tears using 3-tesla MRI vs. 3-tesla MRA: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Various protocols exist for magnetic resonance arthrogram (MRA) of
      the shoulder, including 3D isotropic scanning and positioning in neutral (2D
      neutral MRA), or abduction-external-rotation (ABER). HYPOTHESIS: MRA does not
      improve diagnostic accuracy for labral tears when compared to magnetic resonance
      imaging (MRI) performed using 3-Tesla (3T) magnets. METHOD: Systematic review of
      the Cochrane, MEDLINE, and PubMed databases according to PRISMA guidelines.
      Included studies compared 3T MRI or 3T MRA (index tests) to arthroscopic findings
      (reference test). Methodological appraisal performed using QUADAS-2. Pooled
      sensitivity and specificity were calculated. RESULTS: Ten studies including 929
      patients were included. Index test bias and applicability were a concern in the
      majority of studies. The use of arthroscopy as the reference test raised concern
      of verification bias in all studies. For anterior labral lesions, 3T MRI was less
      sensitive (0.83 vs. 0.87 p = 0.083) than 3T 2D neutral MRA. Compared to 3T 2D
      neutral MRA, both 3T 3D Isotropic MRA and 3T ABER MRA significantly improved
      sensitivity (0.87 vs. 0.95 vs. 0.94). For SLAP lesions, 3T 2D neutral MRA was of
      similar sensitivity to 3T MRI (0.84 vs. 0.83, p = 0.575), but less specific (0.99
      vs. 0.92 p < 0.0001). For posterior labral lesions, 3T 2D neutral MRA had greater
      sensitivity than 3T 3D Isotropic MRA and 3T MRI (0.90 vs. 0.83 vs. 0.83).
      CONCLUSIONS: At 3-T, MRA improved sensitivity for diagnosis of anterior and
      posterior labral lesions, but reduced specificity in diagnosis of SLAP tears. 3T
      MRA with ABER positioning further improved sensitivity in diagnosis of anterior
      labral tears. LEVEL OF EVIDENCE: IV.

PMID- 29582142
TI  - Land surface temperature estimating in urbanized landscapes using artificial
      neural networks.
AB  - Scenario-based land surface temperature (LST) modeling is a powerful tool for
      adopting proper urban land use planning policies. In this study, using greater
      Isfahan as a case study, the artificial neural network (ANN) algorithm was
      utilized to explore the non-linear relationships between urban LST and green
      cover spatial patterns derived from Landsat 8 OLI imagery. The model was
      calibrated using two sets of variables: Normalized Difference Built Index (NDBI)
      and Normalized Difference Vegetation Index (NDVI). Furthermore, Compact
      Development Scenario (CDS) and Green Development Scenario (GDS) were defined. The
      results showed that GDS is more successful in mitigating urban LST (mean LST =
      40.93) compared to CDS (mean LST = 44.88). In addition, urban LST retrieved from
      the CDS was more accurate in terms of ANOVA significance (sig = 0.043) than the
      GDS (sig = 0.010). The findings of this study suggest that developing green
      spaces is a key strategy to combat against the risk of LST concerns in urban
      areas.

PMID- 29582144
TI  - Peritoneal drainage in pneumoperitoneum in extremely low birth weight infants.
AB  - : The aim was to determine if peritoneal drainage (PD) is a suitable treatment
      for pneumoperitoneum in extremely low birth weight (ELBW) infants. A
      retrospective chart review of 42 ELBW infants with pneumoperitoneum at the
      University Hospital of Cologne between November 2014 and April 2017 was
      performed. Forty-two infants with a median birth weight of 645 g (interquartile
      range (IQR) 550, 806) and a median gestational age of 24.3 weeks (IQR 23.2, 25.6)
      were treated for pneumoperitoneum. Twenty-six (62%) received PD, and in ten
      (38%), the drain could be removed without further intervention. Infants in the PD
      group were of significantly lower birth weight (622g vs. 750 g), age (4.5 vs.
      10.0 days), and weight at diagnosis (538 vs. 778 g). The mortality in the PD
      group was 15% at 90 days of life, but no patient deceased in the primary
      laparotomy group. CONCLUSION: We suggest PD with close evaluation of drainage and
      clinical course as an alternative treatment for pneumoperitoneum in ELBW infants
      allowing bridging the vulnerable first days of life until these infants are in a
      more stable condition. Despite not reaching statistical significance in our
      series, PD showed the trend towards higher mortality. What is known: *
      Pneumoperitoneum is traditionally treated with laparotomy, but placement of
      peritoneal drainage (PD) is a valuable treatment option. * Previous randomized
      controlled trials have shown no significant differences in mortality for PD
      versus laparotomy. What is new: * In our cohort, 38% of the infants with PD could
      be saved from secondary laparotomy, but in the PD group there was a trend towards
      higher mortality. * PD allows bridging the vulnerable first days of life until
      ELBW infants are in a more stable condition for possible laparotomy.

PMID- 29582143
TI  - Genetic contribution to vestibular diseases.
AB  - Growing evidence supports the contribution of allelic variation to vestibular
      disorders. Heritability attributed to rare allelic variants is found in familial
      vestibular syndromes such as enlarged vestibular aqueduct syndrome or familial
      Meniere disease. However, the involvement of common allelic variants as key
      regulators of physiological processes in common and rare vestibular diseases is
      starting to be deciphered, including motion sickness or sporadic Meniere disease.
      The genetic contribution to most of the vestibular disorders is still largely
      unknown. This review will outline the role of common and rare variants in human
      genome to episodic vestibular syndromes, progressive vestibular syndrome, and
      hereditary sensorineural hearing loss associated with vestibular phenotype.
      Future genomic studies and network analyses of omic data will clarify the pathway
      towards a personalized stratification of treatments.

PMID- 29582145
TI  - Enhanced recovery after posterior minimally invasive total hip arthroplasty with
      continuous intraarticular anaesthesia.
AB  - BACKGROUND: The aim of this study was to evaluate the possible complications
      specific to the continuous intraarticular anaesthesia (CIA) in a minimally
      invasive posterior approach in total hip arthroplasty and its possible effects on
      the recovery, especially on pain and the length of hospitalisation. MATERIALS AND
      METHODS: The surgical procedure is first precisely described step by step with
      numerous per-operating photographs. Particular technical points are detailed. The
      errors to be avoided are specified. A prospective series of 70 first-line total
      hip arthroplasties (one half with and one half without CIA) are analysed for the
      well-known results of total hip arthroplasty but specifically assessing: (a)
      specific possible complications to the minimally invasive posterior technique
      with the prolonged local anaesthesia and (b) effects on pain, duration of
      hospitalisation and satisfaction in patients (questionnaire). RESULTS: (a) Very
      low level of immediate post-operative pain was observed in almost all of the
      patients. (b) Patient satisfaction was high in our series. (c) A repeated
      education was provided multiple times to avoid specific complications following
      the absence of pain and consequent inattention. DISCUSSION AND CONCLUSION: The
      minimally invasive posterior approach with continuous intraarticular anaesthesia
      is an entirely reliable hip arthroplasty procedure. The patients exhibited a
      significantly less pain and a fast rate of recovery, but preparatory education
      must be even more significant.

PMID- 29582146
TI  - Generalizing the results: how can we improve our reports?

PMID- 29582147
TI  - Answer to the Letter to the Editor of Jie Weng et al. concerning, "Relationship
      between preoperative serum rapid turnover proteins and early-stage surgical wound
      infection after spine surgery" by D. Kudo et al. (Eur Spine J; 2016:
      doi:10.1007/s00586-016-4855-z).

PMID- 29582148
TI  - Assessment of dialysis adequacy: beyond urea kinetic measurements.
AB  - Adequacy of dialysis is a term that has been used for many years based on
      measurement of small solute clearance using urea and creatinine. This has been
      shown in some but not all studies in adults to correlate with survival. However,
      small solute clearance is just one minor part of the effectiveness of dialysis
      and in fact 'optimum' dialysis, rather than 'adequate' dialysis is what most
      paediatric nephrologists would want for their patients. Additional ways to assess
      the success of dialysis in children would include dialysis access complications
      and longevity, preservation of residual kidney function, body composition,
      biochemical and haematological control, nutrition and growth, discomfort during
      the dialysis process and psychosocial adjustment including hospitalisation and
      school attendance. These criteria need to be balanced against a dialysis
      programme that has the least possible adverse effects on quality of life.

PMID- 29582149
TI  - Obtaining central access in challenging pediatric patients.
AB  - PURPOSE: Central catheter placement is one of the most commonly performed
      procedures by pediatric surgeons. Here, we present a case series of patients
      where central access was obtained at our institution with the utilization of a
      novel ultrasound-guided technique. This series represents the first of its kind
      where the native, parent vessels were inaccessible, resulting in a challenging
      situation for providers. METHODS: A retrospective chart review was performed in
      pediatric patients (0-17 years) at a tertiary care institution between July 2012
      and November 2017 on all central line procedures where ultrasound was utilized to
      cannulate the brachiocephalic or superior vena cava in face of proximal
      occlusion. Our group has previous experience utilizing an image-guided in-plane
      approach to central line placement in the pediatric population. Demographics,
      operative characteristics, and postoperative complications were reviewed.
      RESULTS: A total of 11 procedures were included in this case series where the BC
      (N = 9) or SVC (N = 2) were cannulated for access. Internal jugular vein
      cannulation was attempted on each patient unless preoperative imaging
      demonstrated occlusion. The median operative time was 43 +/- 23 min. Most
      procedures were performed on the right sided (63%), with catheters ranging from
      4.2F single lumen to 14F double lumen. Since being placed, three (27%) catheters
      have been removed, with one due to non-use, one due to sepsis, and the final one
      due to malposition. CONCLUSION: With the continued need for long-term central
      access in the pediatric population, distal vein occlusion or inaccessibility can
      prove challenging when attempting to obtain central access. Here, demonstrated a
      safe alternative technique that provides an additional option in the pediatric
      surgeon's armamentarium for patients with difficult central access.

PMID- 29582150
TI  - Evaluation of artifact-corrected electroencephalographic (EEG) training: a pilot
      study.
AB  - This double-blind study examined the effect of electromyographical (EMG)
      artifacts, which contaminate electroencephalographical (EEG) signals, by
      comparing artifact-corrected (AC) and non-artifact-corrected (NAC) neurofeedback
      (NF) training procedures. 14 unmedicated college students were randomly assigned
      to two groups: AC (n = 7) or NAC (n = 7). Both groups received 12 sessions of NF
      and were trained using identical NF treatment protocols to reduce their
      theta/beta power ratios (TBPR). Outcomes on a continuous performance test
      revealed that the AC group had statistically significant increases across
      measures of auditory and visual attention. The NAC group showed smaller gains
      that only reached statistical significance on measures of visual attention. Only
      the AC group reduced their TBPR, the NAC group did not. AC NF appears to play an
      important role during training that leads to improvements in both auditory and
      visual attention. Additional research is required to confirm the results of this
      study.

PMID- 29582152
TI  - Implementation and evaluation of an interdisciplinary preventive program to
      prevent early childhood caries.
AB  - OBJECTIVES: Since early childhood caries (ECC) is a major disease in the public
      health sector, an interdisciplinary prevention concept to avert this disease was
      developed, launched in a project region, and evaluated. It was examined whether
      the emergence of ECC could be prevented or curbed with the newly developed
      program. MATERIALS AND METHODS: The program encompasses seven pulses of
      information from an interdisciplinary team (gynecologists, midwives,
      pediatricians, dentists, municipal social services, and the public health
      office). The primary dependent variables were caries experience and prevalence
      among the 3- to 4-year-olds who took part in the ECC prevention program, compared
      to children of the same age without such measures. The effect of the prevention
      program was assessed by means of a "historical" comparison. The dental diagnoses
      were performed by two calibrated dentists based on the "ICDAS collapsed." Data on
      diet and preventive behavior were gathered using a standardized parental
      questionnaire. The significance was tested using the nonparametric Mann-Whitney U
      test. RESULTS: There were 661 3- to 4-year-olds in the control group and 706 in
      the test group. The mean d3-6mf-t for the control group (0.92) was significantly
      higher than that for the test group (0.46). While 78.8% of the children examined
      in the control group exhibited predominantly sound primary dentition, this was
      the case for 86.3% of the test group. The proportion of children with S-ECC was
      7.9% in the test group and 14.5% in the control group. The test group differed
      significantly from the control group both in terms of reported diet and dental
      hygiene habits. CONCLUSIONS AND CLINICAL RELEVANCE: The interdisciplinary
      prevention program presented here is an effective concept for preventing ECC and
      considerably helps reduce problems in the treatment of small children.

PMID- 29582151
TI  - Bacterial exopolysaccharides as a modern biotechnological tool for modification
      of fungal laccase properties and metal ion binding.
AB  - Four bacterial EPSs extracted from Rhizobium leguminosarum bv. trifolii Rt24.2,
      Sinorhizobium meliloti Rm1021, Bradyrhizobium japonicum USDA110, and
      Bradyrhizobium elkanii USDA76 were determined towards their metal ion adsorption
      properties and possible modification of Cerrena unicolor laccase properties. The
      highest magnesium and iron ion-sorption capacity (~ 42 and ~ 14.5%, respectively)
      was observed for EPS isolated from B. japonicum USDA110. An evident influence of
      EPSs on the stability of laccase compared to the control values (without EPSs)
      was shown after 30-day incubation at 25  degrees C. The residual activity of
      laccases was obtained in the presence of Rh76EPS and Rh1021EPS, i.e., 49.5 and
      41.5% of the initial catalytic activity, respectively. This result was confirmed
      by native PAGE electrophoresis. The EPS effect on laccase stability at different
      pH (from 3.8 to 7.0) was also estimated. The most significant changes at the
      optimum pH value (pH 5.8) was observed in samples of laccase stabilized by
      Rh76EPS and Rh1021EPS. Cyclic voltamperometry was used for analysis of
      electrochemical parameters of laccase stabilized by bacterial EPS and immobilized
      on single-walled carbon nanotubes (SWCNTs) with aryl residues. Laccases with
      Rh76EPS and Rh1021EPS had an evident shift of the value of the redox potential
      compared to the control without EPS addition. In conclusion, the results obtained
      in this work present a new potential use of bacterial EPSs as a metal-binding
      component and a modulator of laccase properties especially stability of enzyme
      activity, which can be a very effective tool in biotechnology and industrial
      applications.

PMID- 29582153
TI  - Predictive factors of neurological recovery after chronic craniovertebral
      brainstem compression.
AB  - BACKGROUND: Neurologic manifestations of craniovertebral junction (CVJ) disease
      may generate dramatic brainstem damage, which could evolve to paralysis. In most
      cases, patients are referred with advanced neurological symptoms such as
      tetraplegia/paresis. The aim of this study was to identify predictive factors of
      favorable neurological evolution after non-traumatic brainstem compression.
      METHODS: A prospective study evaluated 143 consecutive patients who had undergone
      CVJ anterior brainstem decompression. The mean age was 45.1 +/- 19.1 years. The
      study analyzed clinical, surgical, and imagery characters to determine predictive
      factors of neurological improvement. RESULTS: The mean follow-up of our series
      was 10.2 years (range 0.5-23.9). Seventy-one (49.6%) presented initial
      tetrapalsies resulting from spinal cord compression. Multivariable analysis
      revealed that Frankel score [odds ratio (OR) 5.7, CI 95% 1.01-31.8; p < 0.04] and
      preoperative symptoms < 6 months [OR 0.33, CI 95% 0.125-0.9; p < 0.025] were
      independently associated with partial neurological improvement, while the only
      independent factor associated with total neurologic recovery was the preoperative
      symptom evolution <6 months [odd ratio (OR) 4.3, CI 95% 1.6-11.4; p < 0.003].
      None of the following were identified as predictive factors: demographic
      characteristics, medical history, the etiology of compression, or initial spinal
      cord MRI. CONCLUSION: The earlier the decompression is performed, the better the
      neurological improvement. Whatever the initial Frankel score, if neurological
      palsy or disorders evolved for less than 6 months, complete recovery is possible.

PMID- 29582155
TI  - Foreword for Festschrift for Peter's 80th birthday.

PMID- 29582154
TI  - Association of body mass index with chronic pain prevalence: a large population
      based cross-sectional study in Japan.
AB  - PURPOSE: The aim of this study was to examine the association between body mass
      index and chronic pain. METHODS: The outcome was chronic pain prevalence by body
      mass index (BMI). BMIs of less than 18.5, 18.5-25.0, 25.0-30.0, and 30.0 or over
      kg/m2 were defined as underweight, normal weight, overweight, and obese.
      SUBJECTS: We used data from 4993 participants (2464 men and 2529 women aged 20-79
      years) of the Pain Associated Cross-sectional Epidemiological survey in Japan.
      Sex-stratified multivariable-adjusted odds ratios were calculated with 95%
      confidence intervals using a logistic regression model including age, smoking,
      exercise, sleep time, monthly household expenditure, and presence of severe
      depression. We analyzed all ages and age subgroups, 20-49 and 50-79 years.
      RESULTS: The prevalence of chronic pain was higher among underweight, overweight,
      and obese male respondents than those reporting normal weight, with multivariable
      odds ratios of 1.52 (1.03-2.25), 1.55 (1.26-1.91), and 1.71 (1.12-2.60).
      According to underweight, only older men showed higher prevalence of chronic pain
      than normal weight men with odd ratios, 2.19 (1.14-4.20). Being overweight and
      obese were also associated with chronic pain in women; multivariable odds ratios
      were 1.48 (1.14-1.93) and 2.09 (1.20-3.64). Being underweight was not associated
      with chronic pain. CONCLUSION: There was a U-shaped association between BMI and
      chronic pain prevalence among men >= 50 years, and a dose-response association
      among women. Our finding suggests that underweight should be considered in older
      men suffering chronic pain.

PMID- 29582156
TI  - Groundwater contamination by polycyclic aromatic hydrocarbon due to diesel spill
      from a telecom base station in a Nigerian City: assessment of human health risk
      exposure.
AB  - Diesel pollution of groundwater poses great threat to public health, mainly as a
      result of the constituent polycyclic aromatic hydrocarbons (PAHs). In this study,
      the human health risk exposure to polycyclic aromatic hydrocarbons (PAHs) in
      diesel contaminated groundwater used by several families at Ring Road, Jos,
      Nigeria (as caused by diesel spill from a telecom base station) was assessed.
      Prior to the groundwater being treated, the residents were using the water after
      scooping off the visible diesel sheen for purposes of cooking, washing, and
      bathing. Until this study, it is not clear whether the groundwater contamination
      had resulted in sub-chronic exposure of the residents using the water to
      polycyclic aromatic hydrocarbons (PAHs) to the extent of the PAHs posing a health
      risk. The diesel contaminated groundwater and uncontaminated nearby groundwater
      (control) were collected and analyzed for PAHs using gas chromatography-mass
      spectrometry (GC-MS). The dosage of the dermal and oral ingestion entry routes of
      PAHs was determined. The estimation of the non-carcinogenic health risk was via
      hazard quotients (HQ) and the associated hazard index (HI), while the estimation
      of the carcinogenic health risk was via lifetime cancer risks (LCR) and the
      associated risk index (RI). Obtained results indicate that the exposure of the
      residents to the PAHs may have made them susceptible to the risk of non
      carcinogenic health effects of benzo(a)pyrene and the carcinogenic health effects
      of benzo(a)anthracene and benzo(a)pyrene.

PMID- 29582157
TI  - Next-generation sequencing reveals genetic landscape in 46, XY disorders of
      sexual development patients with variable phenotypes.
AB  - Disorders of sexual development (DSD) are rare congenital conditions in which
      chromosomal, gonadal, or anatomical sex is atypical. Currently, less than 20% of
      patients receive an accurate genetic diagnosis. Targeted next-generation
      sequencing, consisting of 33 candidate genes and 47 genes involved in sexual
      differentiation and development, was performed on 70 46, XY DSD patients.
      Functional assays were performed to evaluate the expression and transcriptional
      activity of one reported and nine novel mutations of NR5A1. In total, 113
      mutations, including 86 novel and 27 reported sites in 40 genes, were identified
      in 52 patients. Among them, 37 mutations from 19 genes were first identified in
      46, XY DSD patients, including EGF, LHX9, and CST9. Nine patients displayed
      biallelic mutations, 12 had mutations in sex chromosome genes and 14 had
      monoallelic mutations in NR5A1, BMP4, and WT1. Higher frequency mutations were
      identified in AR, SRD5A2, and NR5A1. Six missense, one frameshift, and one three
      nucleotide deletion mutations of NR5A1 were shown to impair the transactivation
      ability with an altered nuclear aggregation of p.T29K and p.N44del variants.
      Multiple genetic mutations were identified in 33 of the 70 patients. The targeted
      sequencing panel provides an efficient method for the etiological diagnosis of
      46, XY DSD patients and expands the candidate genes and inherited patterns.

PMID- 29582158
TI  - Demonstrating PM2.5 and road-side dust pollution by heavy metals along Thika
      superhighway in Kenya, sub-Saharan Africa.
AB  - This study assessed the level of heavy metal in roadside dust and PM2.5 mass
      concentrations along Thika superhighway in Kenya. Thika superhighway is one of
      the busiest roads in Kenya, linking Thika town with Nairobi. Triplicate road dust
      samples collected from 12 locations were analysed for lead (Pb), chromium (Cr),
      cadmium (Cd), nickel (Ni), zinc (Zn), and copper (Cu) using atomic absorption
      spectrophotometry (AAS). PM2.5 samples were collected on pre-weighed Teflon
      filters using a BGI personal sampler and the filters were then reweighed. The
      ranges of metal concentrations were 39-101 MUg/g for Cu, 95-262 MUg/g for Zn, 9
      28 MUg/g for Cd, 14-24 MUg/g for Ni, 13-30 MUg/g for Cr, and 20-80 MUg/g for Pb.
      The concentrations of heavy metals were generally highly correlated, indicating a
      common anthropogenic source of the pollutants. The results showed that the
      majority of the measured heavy metals were above the background concentration,
      and in particular, Cd, Pb, and Zn levels indicated moderate to high
      contamination. Though not directly comparable due to different sampling
      timeframes (8 h in this study and 24 h for guideline values), PM2.5 for all sites
      exceeds the daily WHO PM2.5 guidelines of 25 MUg/m3. This poses a health risk to
      people using and working close to Thika superhighway, for example, local
      residents, traffic police, street vendors, and people operating small businesses.
      PM2.5 levels were higher for sites closer to Nairobi which could be attributed to
      increased vehicular traffic towards Nairobi from Thika. This study provides some
      evidence of the air pollution problem arising from vehicular traffic in
      developing parts of the world and gives an indication of the potential health
      impacts. It also highlights the need for source apportionment studies to
      determine contributions of anthropogenic emissions to air pollution, as well as
      long-term sampling studies that can be used to fully understand spatiotemporal
      patterns in air pollution within developing regions.

PMID- 29582159
TI  - In Vitro Assessment of Spray Deposition Patterns in a Pediatric (12 Year-Old)
      Nasal Cavity Model.
AB  - PURPOSE: Nasal sprays available for the treatment of cold and allergy symptoms
      currently use identical formulations and devices for adults as well as for
      children. Due to the obvious differences between the nasal airway dimensions of a
      child and those of an adult, the performance of nasal sprays in children was
      evaluated. METHODS: Deposition patterns of nasal sprays administered to children
      were tested using a nasal cast based on MRI images obtained from a 12 year old
      child's nasal cavity. Test formulations emitting a range of spray patterns were
      investigated by actuating the device into the pediatric nasal cast under
      controlled conditions. RESULTS: The results showed that the nasal sprays impacted
      in the anterior region of the 12 year old child's nasal cavity, and only limited
      spray entered the turbinate region - the effect site for most topical drugs and
      the primary absorptive region for systemically absorbed drugs. CONCLUSION:
      Differences in deposition patterns following the administration of nasal sprays
      to adults and children may lead to differences in efficacy between these
      populations. Greater anterior deposition in children may result in decreased
      effectiveness, greater anterior dosage form loss, and the increased potential for
      patient non-compliance.

PMID- 29582161
TI  - Sex differences in the association of psychological status with measures of
      physical activity and sedentary behaviour in adults with type 2 diabetes.
AB  - AIM: To assess the association of psychological variables on leisure-time
      physical activity and sedentary time in men and women with type 2 diabetes
      mellitus (T2D). METHODS: In this cross-sectional study, we evaluated 163 patients
      with T2D, consecutively recruited at the Diabetes Centre of the Verona General
      Hospital. Scores on depression and anxiety symptoms, psychosocial factors
      (including self-efficacy, perceived interference, perceived severity, social
      support, misguided support behaviour, spouse's positive behaviour), physical
      activity and time spent sitting were ascertained using questionnaires responses
      to the Beck Depression Inventory-II, Beck Anxiety Inventory, Multidimensional
      Diabetes Questionnaire, International Physical Activity Questionnaire. RESULTS:
      Physical activity was significantly associated with higher social support in
      women and with increased self-efficacy in men. Sedentary time was significantly
      associated with higher perceived interference, anxiety and depressive symptoms,
      and with reduced diabetes self-efficacy in women, while it was associated solely
      with anxiety in men. Depressive symptoms and self-efficacy in women and anxiety
      symptoms in men were independent predictors of sedentary time when entered in a
      multivariable regression model also including age, BMI, haemoglobin A1c, diabetes
      duration, perceived interference and self-efficacy as covariates. CONCLUSIONS:
      Lower self-efficacy and higher symptoms of depression were closely associated
      with increased sedentary time in women, but not in men, with T2D. It is possible
      that individualized behavioural interventions designed to reduce depressive
      symptoms and to improve diabetes self-efficacy would ultimately reduce sedentary
      behaviours, particularly in women with T2D.

PMID- 29582160
TI  - Screening and diagnosis of gestational diabetes in India: a systematic review and
      meta-analysis.
AB  - AIMS: Although diabetes is rapidly increasing in India, there is no national
      consensus on best practices for screening, diagnosis, and management of
      gestational diabetes mellitus (GDM). The goal of this study was to systematically
      review the literature for studies reporting the prevalence and screening and
      diagnostic methods for gestational diabetes in India. METHODS: We searched
      MEDLINE, Embase, and POPLINE for studies on screening for GDM in India. We
      included English-language full reports and conference abstracts of cross
      sectional studies, prospective, and retrospective cohorts that reported the
      screening method and prevalence of GDM. We performed descriptive analysis on all
      studies and meta-analysis, meta-regression, and subgroup meta-analysis on studies
      with medium or low risk of bias. RESULTS: We included 64 studies reporting 90
      prevalence estimates. Prevalence estimates ranged from 0 to 41.9%. Subset meta
      analyses showed that the IADPSG diagnostic criteria found significantly more GDM
      cases (prevalence = 19.19% [15.5, 23.6], p < 0.05) than the WHO 1999 criteria
      (10.13% [8.17, 12.50]) and DIPSI criteria (7.37% [5.2, 10.16]). Studies that
      compared the IADPSG and WHO 1999 criteria showed poor positive agreement (33
      79%). Studies specifying time of GDM diagnosis showed that patients (11-60%)
      develop GDM as early as the first trimester, but many GDM cases (16-40%) are
      missed if screened only at first visit. CONCLUSIONS: In India, prevalence
      estimates of GDM vary substantially by diagnostic criteria. When evaluating
      screening and diagnostic criteria for GDM, providers should consider their
      patients' needs and correlate screening criteria with pregnancy outcomes.

PMID- 29582162
TI  - Low adherence to the western and high adherence to the mediterranean dietary
      patterns could prevent colorectal cancer.
AB  - PURPOSE: To assess if the associations found between three previously identified
      dietary patterns with breast, prostate and gastric cancer are also observed for
      colorectal cancer (CRC). METHODS: MCC-Spain is a multicase-control study that
      collected information of 1629 incident cases of CRC and 3509 population-based
      controls from 11 Spanish provinces. Western, Prudent and Mediterranean data
      driven dietary patterns-derived in another Spanish case-control study-were
      reconstructed in MCC-Spain. Their association with CRC was assessed using mixed
      multivariable logistic regression models considering a possible interaction with
      sex. Risk by tumor site (proximal colon, distal colon, and rectum) was evaluated
      using multinomial regression models. RESULTS: While no effect of the Prudent
      pattern on CRC risk was observed, a high adherence to the Western dietary pattern
      was associated with increased CRC risk for both males [ORfourth(Q4) vs.
      first(Q1)quartile (95% CI): 1.45 (1.11;1.91)] and females [ORQ4 vs. Q1 (95% CI):
      1.50 (1.07;2.09)] but seem to be confined to distal colon [ORfourth(Q4) vs.
      first(Q1)quartile (95% CI): 2.02 (1.44;2.84)] and rectal [ORQ4 vs. Q1 (95% CI):
      1.46 (1.05;2.01)] tumors. The protective effect of the Mediterranean dietary
      pattern against CRC was observed for both sexes [males: ORQ4 vs. Q1 (95% CI):
      0.71 (0.55;0.92); females: ORQ4 vs. Q1 (95% CI): 0.56 (0.40;0.77)] and for all
      cancer sites: proximal colon [ORQ4 vs. Q1 (95% CI): 0.70 (0.51;0.97)], distal
      colon [ORQ4 vs. Q1 (95% CI): 0.65 (0.48;0.89)], and rectum (ORQ4 vs. Q1 (95% CI):
      0.60 (0.45;0.81)]. CONCLUSION: Our results are consistent with most of the
      associations previously found between these patterns and breast, prostate and
      gastric cancer risk and indicate that consuming whole fruits, vegetables,
      legumes, olive oil, nuts, and fish and avoiding red and processed meat, refined
      grains, sweets, caloric drinks, juices, convenience food, and sauces might reduce
      CRC risk.

PMID- 29582163
TI  - Co-infection with human polyomavirus BK enhances gene expression and replication
      of human adenovirus.
AB  - Immunocompromised patients are susceptible to multiple viral infections. Relevant
      interactions between co-infecting viruses might result from viral regulatory
      genes which trans-activate or repress the expression of host cell genes as well
      as the genes of any co-infecting virus. The aim of the current study was to show
      that the replication of human adenovirus 5 is enhanced by co-infection with BK
      polyomavirus and is associated with increased expression of proteins including
      early region 4 open reading frame 1 and both the large tumor antigen and small
      tumor antigen. Clinical samples of whole blood and urine from 156 hematopoietic
      stem cell transplant recipients were tested. We also inoculated adenocarcinomic
      human alveolar basal epithelial cells with both human adenovirus 5 and BK
      polyomavirus to evaluate if co-infection of viruses affected their replication.
      Data showed that adenovirus load was significantly higher in the plasma (mean 7.5
      x 103 +/- 8.5 x 102 copies/ml) and urine (mean 1.9 x 103 +/- 8.0 x 102 copies/ml)
      of samples from patients with co-infections, in comparison to samples from
      patients with isolated adenovirus infection. In vitro co-infection led to an
      increased (8.6 times) expression of the adenovirus early region 4 open reading
      frame gene 48 hours post-inoculation. The expression of the early region 4 open
      reading frame gene positively correlated with the expression of BK polyomavirus
      large tumor antigen (r = 0.90, p < 0.0001) and small tumor antigen (r = 0.83, p <
      0.001) genes. The enhanced expression of the early region 4 open reading frame
      gene due to co-infection with BK polyomavirus was associated with enhanced
      adenovirus, but not BK polyomavirus, replication. The current study provides
      evidence that co-infection of adenovirus and BK polyomavirus contributes to
      enhanced adenovirus replication. Data obtained from this study may have
      significant importance in the clinical setting.

PMID- 29582164
TI  - Induction of a high-titered antibody response using HIV gag-EV71 VP1-based virus
      like particles with the capacity to protect newborn mice challenged with a lethal
      dose of enterovirus 71.
AB  - Enterovirus 71 (EV71) is the most frequently detected causative agent in hand,
      foot, and mouth disease (HFMD) and is a serious threat to public health in the
      Asia-Pacific region. Many EV71 vaccines are under development worldwide, and
      although both inactivated virus vaccines and virus-like particles (VLPs) are
      considered to be effective, the main focus has been on inactivated EV71vaccines.
      There have been very few studies on EV71 VLPs. In this study, using a strategy
      based on HIV gag VLPs, we constructed a gag-VP1 fusion gene to generate a
      recombinant baculovirus expressing the EV71 structural protein VP1 together with
      gag, which was then used to infect TN5 cells to form VLPs. The VLPs were
      characterized using transmission electron microscopy, electrophoresis and
      staining with Coomassie blue, and Western blotting. Mice immunized with gag-VP1
      VLPs showed strong humoral and cellular immune responses. Finally, immunization
      of female mice with gag-VP1 VLPs provided effective protection of their newborn
      offspring against challenge with a lethal dose EV71. These results demonstrate a
      successful approach for producing EV71 VP1 VLPs based on the ability of HIV gag
      to self-assemble, thus providing a good foundation for producing high-titered
      anti-EV71 antibody by immunization with VLP-based gag EV71 VP1 protein.

PMID- 29582165
TI  - Using genomic analysis to identify tomato Tm-2 resistance-breaking mutations and
      their underlying evolutionary path in a new and emerging tobamovirus.
AB  - In September 2014, a new tobamovirus was discovered in Israel that was able to
      break Tm-2-mediated resistance in tomato that had lasted 55 years. The virus was
      isolated, and sequencing of its genome showed it to be tomato brown rugose fruit
      virus (ToBRFV), a new tobamovirus recently identified in Jordan. Previous studies
      on mutant viruses that cause resistance breaking, including Tm-2-mediated
      resistance, demonstrated that this phenotype had resulted from only a few
      mutations. Identification of important residues in resistance breakers is
      hindered by significant background variation, with 9-15% variability in the
      genomic sequences of known isolates. To understand the evolutionary path leading
      to the emergence of this resistance breaker, we performed a comprehensive
      phylogenetic analysis and genomic comparison of different tobamoviruses, followed
      by molecular modeling of the viral helicase. The phylogenetic location of the
      resistance-breaking genes was found to be among host-shifting clades, and this,
      together with the observation of a relatively low mutation rate, suggests that a
      host shift contributed to the emergence of this new virus. Our comparative
      genomic analysis identified twelve potential resistance-breaking mutations in the
      viral movement protein (MP), the primary target of the related Tm-2 resistance,
      and nine in its replicase. Finally, molecular modeling of the helicase enabled
      the identification of three additional potential resistance-breaking mutations.

PMID- 29582166
TI  - Restoring the IL-1beta/NF-kappaB-induced impaired chondrogenesis by diallyl
      disulfide in human adipose-derived mesenchymal stem cells via attenuation of
      reactive oxygen species and elevation of antioxidant enzymes.
AB  - Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured
      articular cartilage are not effective enough in osteoarthritis (OA). Due to the
      enhanced inflammation and oxidative stress in OA microenvironment,
      differentiation of MSCs into chondrocytes would be impaired. This study aims to
      explore the effects of diallyl disulfide (DADS) on IL-1beta-mediated inflammation
      and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs)
      during chondrogenesis. MTT assay was employed to examine the effects of various
      concentrations of DADS on the viability of hADSCs at different time scales to
      obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1beta
      induced intracellular ROS generation and lipid peroxidation were evaluated in
      hADSCs. Western blotting was used to analyze the protein expression levels of
      IkappaBalpha (np), IkappaBalpha (p), NF-kappaB (np) and NF-kappaB (p).
      Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and
      chondrogenic markers at days 7, 14 and 21 of differentiation were measured using
      qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA
      expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid
      peroxidation, IkappaBalpha activation and NF-kappaB nuclear translocation in
      hADSCs treated with IL-1beta. In addition, DADS could significantly increase the
      expression levels of IL-1beta-induced impaired chondrogenic marker genes in
      differentiated hADSCs. Treatment with DADS may provide an effective approach to
      prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes
      of chondrocyte cell death and enhance the protective anabolic effects by
      promoting chondrogenesis associated gene expressions in hADSCs exposed to OA
      condition.

PMID- 29582167
TI  - Amniotic membrane extract differentially regulates human peripheral blood T cell
      subsets, monocyte subpopulations and myeloid dendritic cells.
AB  - The discovery of the immunoregulatory potential of human amniotic membrane (hAM)
      propelled several studies focusing on its application for the treatment of
      immunological disorders. However, there is little information regarding the
      effects of hAM on distinct activation and differentiation stages of immune cells.
      Here, we aim to investigate the effect of human amniotic membrane extract (hAME)
      on the pattern of cytokine production by T cells, monocytes and myeloid dendritic
      cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from
      eight healthy individuals were stimulated in vitro in the presence or absence of
      hAME. Mitogen-induced proliferation of PBMCs and cytokine production among the
      distinct T cell functional compartments, monocyte subpopulations and mDCs were
      evaluated. hAME displayed an anti-proliferative effect and decreased the
      frequency of T cells producing tumor necrosis factor (TNF)alpha, interferon
      (IFN)gamma and interleukin (IL)-2, for all T cell functional compartments. The
      frequency of IL-17 and IL-9-producing T cells was also reduced. The inhibition of
      mRNA expression of granzyme B, perforin and NKG2D by CD8+ T cells and gammadelta
      T cells and the augment of FoxP3 and IL-10 in CD4+ T cells and IL-10 in
      regulatory T cells were also observed. Furthermore, hAME inhibited IFNgamma
      induced protein (IP)-10 expression by classical and non-classical monocytes,
      without hampering the production of TNFalpha and IL-6 by monocytes and mDCs.
      These results suggest that hAME exerts an anti-inflammatory effect on T cells,
      still at a different extent for distinct T cell functional compartments.

PMID- 29582168
TI  - Underutilized and Under Threat: Environmental Policy as a Tool to Address
      Diabetes Risk.
AB  - PURPOSE OF REVIEW: Diabetes is a burgeoning threat to public health in the USA.
      Importantly, the burden of diabetes is not equally borne across society with
      marked disparities based on geography, race/ethnicity, and income. The etiology
      of global and population-specific diabetes risk remains incompletely understood;
      however, evidence linking environmental toxicants acting as endocrine-disrupting
      chemicals (EDCs), such as particulate matter and arsenic, with diabetes suggests
      that environmental policies could play an important role in diabetes risk
      reduction. RECENT FINDINGS: Evidence suggests that disproportionate exposures to
      EDCs may contribute to subgroup-specific diabetes risk; however, no federal
      policies regulate EDCs linked to diabetes based upon diabetogenic potential.
      Nevertheless, analyses of European Union data indicate that such regulation could
      reduce diabetes-associated costs and disease burden. Federal laws only regulate
      EDCs indirectly. The accumulating evidence linking these chemicals with diabetes
      risk should encourage policymakers to adopt stricter environmental standards that
      consider both health and economic impacts.

PMID- 29582169
TI  - Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular
      analysis and histogenetic evaluation.
AB  - PURPOSE: Medulloblastoma (MDB) is a small cell poorly differentiated embryonal
      tumor of the cerebellum, which more frequently compromises children. Overall
      prognosis is favorable, but dependent of stage, histopathological pattern and
      molecular group. Approximately 30% of the affected patients will die from the
      disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS)
      has been classified MDB into four principal groups: WNT-activated MDB, SHH
      activated MDB, group 3 MDB, and group 4 MDB. WNT-activated MDB is associated to
      monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear
      immunoexpression, and a better prognosis than SHH-activated MDB. DISCUSSION: WNT
      activated tumors account approximately for 10% of cases of MDBs, and are thought
      to arise from cells in the dorsal brain stem/lower rhombic lip progenitor cells.
      SHH-activated MDB more frequently arises in the lateral hemispheres of the
      cerebellum, and clinical outcome in this group is variable. TP53-mutant
      SHHactivated MDB usually shows the large cell/anaplastic pattern, and can be
      related to MYCN amplification, GLI2 amplification and 17p loss. TP53-wildtype SHH
      activated MDB is more commonly of desmoplastic/nodular morphology, and can be
      related to PTCH1 deletion and 10q loss. Gene expression and methylation profiling
      is the gold standard for defining molecular groups of MDB. In
      immunohistochemistry assays, anti-GAB1 antibody expression is positive in tumors
      showing SHH pathway activation or PTCH mutation, while positive immunoexpression
      for YAP1 antibody can be only found in WNT-activated and SHH-activated MDB.

PMID- 29582170
TI  - Management of split cord malformation in children: the Lyon experience.
AB  - INTRODUCTION: Split cord malformation (SCM) is a rare congenital spinal
      abnormality. Clinical presentation varies. Other congenital defects can be
      associated. Management is surgical. MATERIAL AND METHODS: We retrospectively
      reviewed all our SCM cases and reported our experience for its management. From
      1990 to 2014, 37 patients were operated. Five situations lead to the diagnosis
      (orthopedic disorders (n = 8), orthopedic and neurological disorders (n = 16),
      pure neurological disorders (n = 5), no symptoms except cutaneous signs (n = 7),
      antenatal diagnosis (n = 1)). Scoliosis was the most common associated condition.
      The level of the spur was always under T7 except in one case. There were more
      type I (n = 22) than type II (n = 15) SCM. RESULTS: Patients with preoperative
      neurological symptoms (n = 21) were improved in 71.4%. Five out of nine patients
      that had preoperative bladder dysfunction were improved. Eleven patients needed
      surgical correction of the scoliosis. CONCLUSIONS: For us, the surgical procedure
      is mandatory even in case of asymptomatic discovery in order to avoid late
      clinical deterioration. In any case, the filum terminale need to be cut in order
      to untether completely the spinal cord. In case a surgical correction of a spinal
      deformity is needed, we recommend a two-stage surgery, for both SCM type. The SCM
      surgery can stop the evolution of the scoliosis and it may just need an
      orthopedic treatment with a brace.

PMID- 29582171
TI  - Experience in shunt management on revision free survival in infants with
      myelomeningocele.
AB  - OBJECTIVE: Depending on the etiology of hydrocephalus in childhood, the shunt
      therapy still remains challenging due to frequent shunt complications leading to
      possible revisions such as shunt infection or shunt malfunction. In
      myelomeningocele (MMC) patients who often require shunt therapy, higher revisions
      rates were reported. In a single-center retrospective study, experiences on shunt
      regimen on hydrocephalus associated with MMC are presented. METHODS: Data of 160
      infant hydrocephalus cases younger than 1 year of age at the time of implantation
      were retrospectively reviewed from the hospital database. These patients received
      an adjustable differential pressure valve with gravitational unit and antibiotic
      impregnated catheters as a primary or secondary implant during the time period of
      April 2007 to July 2015. The subgroup of infants cases with MMC (n = 44; age 50.6
      +/- 80.6 days) were compared to the remaining cohort of other hydrocephalus
      etiology (control group). The shunt and valve revision free survival rates were
      recorded until July 2017. RESULTS: During the mean follow-up of 48.7 +/- 19.2 (7
      114) months, the shunt revision free survival was 87% at 1 year and 49% at 60
      months in the MMC cohort. The control group showed a shunt survival rate of 68%
      at 1 year and 39% at 60 months. Similarly, the valve revision free survival rate
      showed a significant higher rate of 92% at 1 year and 69% at 60 months in the MMC
      group compared to the control group (75% at 1 year and 51% at 60 months; p <
      0.05). During the entire follow-up period, 37% of the MMC infants underwent a
      revision operation in contrast to the control group of 40%. CONCLUSION: The
      presented shunt strategy showed improved revision free survival rates in infants
      with a MMC-related hydrocephalus in comparison to other etiologies of
      hydrocephalus in infants, which might relate to infection prophylaxis and high
      drainage resistance integrated in the shunt system.

PMID- 29582172
TI  - Gender differences in the presentation of dysphonia related to laryngopharyngeal
      reflux disease: a case-control study.
AB  - OBJECTIVE: To investigate the voice quality impairments in patients with
      laryngopharyngeal reflux (LPR) according to the gender. DESIGN: Controlled multi
      center study. MATERIALS AND METHODS: 80 LPR patients (40 males and 40 females)
      with reflux finding score (RFS) > 7 and reflux symptom index (RSI) > 13 were
      included and clinically compared according to gender. To be considered as LPR
      patients, subjects responded to an empiric therapeutic trial based on
      pantoprazole intake and diet recommendations for 3 months or had positive
      pH/Impedance metry. Voice Handicap Index (VHI); Short Form Healthy Survey 36
      (SF36), blinded Grade, Roughness, Breathiness, Asthenia, Strain and Instability
      (GRBASI); aerodynamic and acoustic measurements were assessed in all patients and
      compared with 80 healthy controls (40 males and 40 females) according to gender.
      RESULTS: The most common reasons for the consultation were, respectively, globus
      sensation in males (22.5%) and dysphonia (27.5%) in female who complained more of
      breathing difficulties and choking episodes related to LPR than males (p =
      0.024). From a quality of life standpoint, female had increased significant
      impact of LPR disease on vitality and mental health than male. Compared to
      healthy subjects, both LPR male and female patients had stronger values of G, R,
      B, S, I, VHI, percent jitter, percent shimmer, and soft palate index than
      controls. In addition, LPR female had stronger values of lowest fundamental
      frequency and all aerodynamic measurements than controls. CONCLUSION: As showed
      in many other laryngeal conditions, voice quality of female could be more
      impaired by LPR than male. Some anatomical, histological and functional factors
      can be suspected and need additional future researches.

PMID- 29582173
TI  - Expression of hormone receptors in oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVES: Hormone receptors play an important role in many types of cancers.
      Alongside factors associated with human papillomavirus (HPV) infection, hormonal
      receptors may impact the tumorigenesis of oropharyngeal cancer. MATERIALS AND
      METHODS: This study consists of 199 consecutive oropharyngeal squamous cell
      carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We
      examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone
      receptor (PR) expressions using immunohistochemistry comparing tumor and patient
      characteristics. RESULTS: AR was expressed in 16%, PR in 27% and ER-beta in 63%
      of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than
      their negative counterparts. High PR expression was associated with poor disease
      specific and locoregional recurrence-free survival. CONCLUSION: AR, PR, and ER
      beta are expressed in OPSCC, and AR and PR expressions are associated with HPV
      and p16 status. Furthermore, PR appears to have prognostic significance. This may
      allow us to investigate the role of anti-hormone receptors in the treatment of
      OPSCC.

PMID- 29582174
TI  - Arterial spin labeling perfusion-weighted MR imaging: correlation of tumor blood
      flow with pathological degree of tumor differentiation, clinical stage and nodal
      metastasis of head and neck squamous cell carcinoma.
AB  - PURPOSE: The prognostic parameters of head and neck squamous cell carcinoma
      (HNSCC) include the pathological degree of tumor differentiation, clinical
      staging, and presence of metastatic cervical lymph nodes. To correlate tumor
      blood flow (TBF) acquired from arterial spin labeling (ASL) perfusion-weighted MR
      imaging with pathological degree of tumor differentiation, clinical stage, and
      nodal metastasis of HNSCC. MATERIALS AND METHODS: Retrospective analysis of 43
      patients (31 male, 12 female with a mean age of 65 years) with HNSCC that
      underwent ASL of head and neck and TBF of HNSCC was calculated. Tumor staging and
      metastatic lymph nodes were determined. The stages of HNSCC were stage 1 (n = 7),
      stage II (n = 12), stage III (n = 11) and stage IV (n = 13). Metastatic cervical
      lymph nodes were seen in 24 patients. The degree of tumor differentiation was
      determined through pathological examination. RESULTS: The mean TBF of poorly and
      undifferentiated HNSCC (157.4 +/- 6.7 mL/100 g/min) was significantly different
      (P = 0.001) than that of well-to-moderately differentiated (142.5 +/- 5.7 mL/100
      g/min) HNSCC. The cut-off TBF used to differentiate well-moderately
      differentiated from poorly and undifferentiated HNSCC was 152 mL/100 g/min with
      an area under the curve of 0.658 and accuracy of 88.4%. The mean TBF of stages I,
      II (146.10 +/- 9.1 mL/100 g/min) was significantly different (P = 0.014) than
      that of stages III, IV (153.33 +/- 9.3 mL/100 g/min) HNSCC. The cut-off TBF used
      to differentiate stages I, II from stages III and IV was 148 mL/100 g/min with an
      area under the curve of 0.701 and accuracy of 69.8%. The TBF was higher in
      patients with metastatic cervical lymph nodes. The cut-off TBF suspect metastatic
      node was 147 mL/100 g/min with an area under the curve of 0.671 and accuracy of
      67.4%. CONCLUSION: TBF is a non-invasive imaging parameter that well correlated
      with pathological degree of tumor differentiation, clinical stage of tumor and
      nodal metastasis of HNSCC.

PMID- 29582175
TI  - Exogenous surfactant as a bridge to prolonged "total lung rest" in severely
      injured patient during extracorporeal membrane oxygenation.
AB  - We report a case of a 20-year-old male patient suffering from motorcycle accident
      complicated by rapid development of severe refractory hypoxemia and hypercapnia
      due to serious bilateral lung contusions and lacerations. Positive pressure
      mechanical ventilation induced pressure-dependent massive air leak from disrupted
      pulmonary tissue. Simultaneous implementation of veno-venous extracorporeal
      membrane oxygenation together with surfactant application allowed prolonged
      disconnection of patient from mechanical ventilation ("total lung rest" mode).
      Despite considerable areas of nonaerated tissue on computed tomography prior to
      the disconnection from mechanical ventilation, almost total functional recovery
      of lungs was eventually achieved.

PMID- 29582176
TI  - Hypoglycemia Prevention by Algorithm Design During Intravenous Insulin Infusion.
AB  - PURPOSE OF REVIEW: This review examines algorithm design features that may reduce
      risk for hypoglycemia while preserving glycemic control during intravenous
      insulin infusion. We focus principally upon algorithms in which the assignment of
      the insulin infusion rate (IR) depends upon maintenance rate of insulin infusion
      (MR) or a multiplier. RECENT FINDINGS: Design features that may mitigate risk for
      hypoglycemia include use of a mid-protocol bolus feature and establishment of a
      low BG threshold for temporary interruption of infusion. Computer-guided dosing
      may improve target attainment without exacerbating risk for hypoglycemia. Column
      assignment (MR) within a tabular user-interpreted algorithm or multiplier may be
      specified initially according to patient characteristics and medical condition
      with revision during treatment based on patient response. We hypothesize that a
      strictly increasing sigmoidal relationship between MR-dependent IR and BG may
      reduce risk for hypoglycemia, in comparison to a linear relationship between
      multiplier-dependent IR and BG. Guidelines are needed that curb excessive up
      titration of MR and recommend periodic pre-emptive trials of MR reduction. Future
      research should foster development of recommendations for "protocol maxima" of IR
      appropriate to patient condition.

PMID- 29582177
TI  - Association between two SCN1A polymorphisms and resistance to sodium channel
      blocking AEDs: a meta-analysis.
AB  - Sodium channel blocking antiepileptic drugs (SCB-AEDs) are common effective
      medications available for epilepsy. However, not all patients respond to this
      regimen and drug resistance is frequently encountered. Rs2298771(c.3184A >
      G/p.Thr1067Ala) and rs3812718(IVS5N +5G > A) polymorphisms are two of the most
      common polymorphisms in the SCN1A gene, which is closely related to resistance to
      SCB-AEDs. Therefore, we have conducted a meta-analysis to investigate the
      contribution of the two polymorphisms to resistance of SCB-AEDs. The PubMed,
      Embase, MEDLINE, and Cochrane Library databases were searched up to September
      2017, for studies on the association of SCN1A polymorphisms with resistance to
      SCB-AEDs. A fixed-effects or random-effects model was used to calculate the
      pooled odds ratios based on the results from the heterogeneity tests. A total of
      eight studies were eligible for the pooled analysis, of which eight studies
      included SCN1A rs3812718 polymorphism and four studies included SCN1A rs2298771
      polymorphism. The results showed that SCN1A rs2298771 polymorphism was
      significantly associated with resistance to SCB-AEDs. (A vs. G: OR = 0.76, 95% CI
      0.61-0.95, P = 0.02; AA vs. AG + GG: OR = 0.71, 95% CI 0.54-0.94, P = 0.022).
      However, no association was observed between SCN1A rs3812718 polymorphism and
      resistance to SCB-AEDs. Our results indicate that the A-allele of SCN1A rs2298771
      polymorphism, especially AA genotype, may play an important role in
      responsiveness to SCB-AEDs, while SCN1A rs3812718 polymorphism is not associated
      with SCB-AEDs.

PMID- 29582178
TI  - Head tremor as a warning symptom of rapidly progressive syringomyelia: a case
      report.

PMID- 29582179
TI  - Non-alcoholic Wernicke-Korsakoff syndrome heralding non-Hodgkin lymphoma
      progression.

PMID- 29582180
TI  - Pain assessment with the revised nociception coma scale and outcomes of patients
      with unresponsive wakefulness syndrome: results from a pilot study.
AB  - The aim of this study was to evaluate whether standardized responses to
      nociceptive pain, assessed with the revised Nociception Coma Scale (NCS-R), were
      correlated with the outcomes of patients with unresponsive wakefulness syndrome
      (UWS) 6 months after admission to a rehabilitation department. We recruited 24
      consecutive patients with UWS. Patients' consciousness levels were assessed with
      the revised Coma Recovery Scale (CRS-R) at admission and 6 months later, and
      their CRS-R scores were correlated with the NCS-R scores at admission. Ten of the
      24 patients with UWS recovered consciousness after 6 months. The NCS-R score at
      admission was correlated with the CRS-R score at admission (P = 0.02), but not
      after 6 months (P = 0.6). Patients with and without consciousness improvement
      after 6 months showed no significant difference in the NCS-R total score and sub
      scores at admission (P values > 0.05). In conclusion, the correlation between NCS
      R and CRS-R scores at admission suggests that the standardized assessment of pain
      parallels patients' levels of consciousness, and may be helpful in the clinical
      evaluation of patients with UWS. Pain response assessed with the NCS-R was not
      related to the 6-month outcomes of patients with UWS.

PMID- 29582181
TI  - Self-Myofascial Vibro-Shearing: a Randomized Controlled Trial of Biomechanical
      and Related Changes in Male Breakdancers.
AB  - BACKGROUND: This randomized controlled trial explored the practicality and
      effectiveness of a novel tool-assisted self-help device, one that combines
      vibrational oscillation, leverage, and the shearing effect from the edges, for
      promoting meaningful changes in key biochemical tissue indices and related
      parameters. METHODS: One hundred and thirteen male breakdancers were randomized
      to an intervention or control group. Individuals assigned to the intervention
      group performed the self-help treatment on the quadriceps and the iliotibial band
      of their right thighs for 8 min, while individuals assigned to the control
      condition merely sat quietly during this period. Various primary outcome measures
      (e.g., elasticity, stiffness, range of motion, pain pressure threshold
      sensitization, and blood flow) were assessed before and after the intervention
      for each participant, with position and posture being standardized throughout.
      Subjective sensations and a measure selected to assess for potential experimental
      demand effects, serving as secondary measures, were also administered pre- to
      post-treatment. RESULTS: Stiffness was significantly reduced for both structures
      (p < 0.001), elasticity and flexibility of the quadriceps were increased
      significantly (p < 0.001 for each), sensitization was significantly lessened (p <
      0.001), and local temperatures increased to a significant degree as well (p <
      0.001) when comparing change scores following application of the self-help tool
      on the treated thighs to those on the untreated thighs. Participants using the
      self-help tool reported their treated leg as being more relaxed, light, and
      stable. CONCLUSIONS: The vibro-shearing manipulation with a muscle-fascia tool
      resulted in significant improvements in various objective mechanical tissue
      properties, range of motion, and pain desensitization in healthy, well
      conditioned dancers. These promising effects for a new tool-assisted self
      treatment indicate further basic investigations are warranted, as are pilot
      investigations with patient populations.

PMID- 29582182
TI  - Diagnosis and Management of Fecal Incontinence.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight current and newer
      therapeutic approaches to treat fecal incontinence in patients who do not respond
      to conservative measures. RECENT FINDINGS: Neurostimulation techniques, injection
      of bulking agents, and radiofrequency energy delivery to the anal canal have been
      proposed and tested for fecal incontinence over the last decade. Sacral
      stimulation is both effective and durable and is now the most popular of the
      invasive techniques whereas percutaneous tibial stimulation, radiofrequency
      energy, and bulking agents are either less effective or their evaluation has been
      handicapped by suboptimal study designs. The precise indications for the new
      vaginal control device and anal plugs remain to be established. The magnetic anal
      sphincter is disappointing. Stem cell therapy is a potentially exciting approach,
      which is in its infancy. There continues to be an unmet need for innovative
      approaches to patients with fecal incontinence who do not respond to conservative
      measures. The efficacy of current and future therapies should be assessed using
      criteria more stringent than has been used in the past to provide a more
      realistic assessment of meaningful efficacy.

PMID- 29582183
TI  - Phenylbutazone (Bute, PBZ, EPZ): one drug across two species.
AB  - In this article we explore the different trajectories of this one drug,
      phenylbutazone, across two species, humans and horses in the period 1950-2000.
      The essay begins by following the introduction of the drug into human medicine in
      the early 1950s. It promised to be a less costly alternative to cortisone, one of
      the "wonder drugs" of the era, in the treatment of rheumatic conditions. Both
      drugs appeared to offer symptomatic relief rather than a cure, and did so with
      the risk of side effects, which with phenylbutazone were potentially so severe
      that it was eventually banned from human use, for all but a few diseases, in the
      early 1980s. Phenylbutazone had been used with other animals for many years
      without the same issues, but in the 1980s its uses in veterinary medicine,
      especially in horses, came under increased scrutiny, but for quite different
      reasons. The focus was primarily the equity, economics, and ethics of competition
      in equine sports, with differences in cross-species biology and medicine playing
      a secondary role. The story of phenylbutazone, a single drug, shows how the
      different biologies and social roles of its human/animal subjects resulted in
      very different and changing uses. While the drug had a seemingly common impact on
      pain and inflammation, there were inter-species differences in the drug's
      metabolism, the conditions treated, dosages, and, crucially, in intended clinical
      outcomes and perceptions of its benefits and risks.

PMID- 29582184
TI  - Small Bowel Amyloidosis.
AB  - PURPOSE OF REVIEW: The goal of this paper is to review the literature on small
      bowel amyloidosis. Our review focuses on the underlying etiology, histopathology,
      clinical features, endoscopic and radiologic findings, and the mainstay of
      management. RECENT FINDINGS: The latest research shows changing epidemiological
      trends of different types of amyloidosis. It also reveals a better understanding
      of its pathophysiology and shows improvement in treatment outcomes. Amyloidosis
      is a group of diseases of multiple etiologies and clinical presentations. It is
      characterized by pathological deposition of insoluble fibrillar proteins within
      various organs leading to disruption of their structure and function. The
      classification of amyloidosis includes primary, secondary, dialysis-related,
      senile, and hereditary. Amyloidosis can be systemic or localized. The incidence
      of AA amyloidosis is declining in frequency. If the gastrointestinal (GI) tract
      is involved, the small intestine is the most commonly affected site. Overall,
      outcomes among patients with newly diagnosed amyloidosis have improved. This
      article focuses on small bowel amyloidosis.

PMID- 29582186
TI  - Decision modelling of non-pharmacological interventions for individuals with
      dementia: a systematic review of methodologies.
AB  - OBJECTIVES: The main objective of this study is to conduct a systematic review to
      identify and discuss methodological issues surrounding decision modelling for
      economic evaluation of non-pharmacological interventions (NPIs) in dementia.
      METHODS: A systematic search was conducted for publications using decision
      modelling to investigate the cost-effectiveness of NPIs for individuals with
      dementia. Search was limited to studies in English. Studies were excluded if they
      evaluated interventions aimed only at caregivers of patients with dementia, or if
      they only included economic evaluation alongside an RCT without additional
      modelling. RESULTS: Two primary, five secondary and three tertiary prevention
      intervention studies were identified and reviewed. Five studies utilised Markov
      models, with others using discrete event, regression-based simulation, and
      decision tree approaches. A number of challenging methodological issues were
      identified, including the use of MMSE-score as the main outcome measure, limited
      number of strategies compared, restricted time horizons, and limited or dated
      data on dementia onset, progression and mortality. Only one of the three tertiary
      prevention studies explicitly considered the effectiveness of pharmacological
      therapies alongside their intervention. CONCLUSIONS: Economic evaluations of NPIs
      in dementia should utilise purposefully-developed decision models, and avoid
      models for evaluation of pharmaceuticals. Broader outcome measures could be a way
      to capture the wide impact of NPIs for dementia in future decision models. It is
      also important to account for the effects of pharmacological therapies alongside
      the NPIs in economic evaluations. Access to more localised and up-to-date data on
      dementia onset, progression and mortality is a priority for accurate prediction.

PMID- 29582185
TI  - Neuromodulation for Chronic Pelvic Pain.
AB  - PURPOSE OF REVIEW: Chronic pelvic pain is a heterogeneous condition that often
      requires multiple physician visits and various treatments prior to achieving an
      acceptable management strategy. Neuromodulation has been used to treat chronic
      pelvic pain that has failed other therapies. RECENT FINDINGS: Numerous modalities
      of neuromodulation have been used to alleviate chronic pelvic pain with promising
      results. Numerous modalities of neuromodulation have demonstrated efficacy in the
      management of pelvic pain. Further investigation is needed to elucidate the most
      effective treatment modality and to identify the patients who would benefit most
      from this therapy.

PMID- 29582187
TI  - Cultural Aspects in Symptomatology, Assessment, and Treatment of Personality
      Disorders.
AB  - PURPOSE OF REVIEW: This review discusses cultural trends, challenges, and
      approaches to assessment and treatment of personality traits and disorders.
      Specific focus include current developments in the Asian, Italian, Iranian, and
      Australian societies, as well as the process of acculturation, following moves
      between cultures with the impact on healthy and disordered personality function.
      RECENT FINDINGS: Each culture with its specific history, dimensions, values, and
      practices influences and gears the individual and family or group in unique ways
      that affect personality functioning. Similarly, each culture provides means of
      protection and assimilation as well as norms for acceptance and denunciations of
      specific behaviors and personality traits. The diagnosis of personality disorders
      and their treatment need to take into consideration the individual in the context
      of the culture and society in which they live. Core personality problems,
      especially emotion dysregulation and interpersonal functioning are specifically
      influenced by cultural norms and context.

PMID- 29582188
TI  - Immune-Mediated Necrotizing Myopathy.
AB  - PURPOSE OF REVIEW: Immune-mediated necrotizing myopathy (IMNM) is a type of
      autoimmune myopathy characterized by relatively severe proximal weakness,
      myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and
      infrequent extra-muscular involvement. Here, we will review the characteristics
      of patients with IMNM. RECENT FINDINGS: Anti-signal recognition particle (SRP)
      and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are
      closely associated with IMNM and define unique subtypes of patients. Importantly,
      the new European Neuromuscular Centre criteria recognize anti-SRP myopathy, anti
      HMGCR myopathy, and autoantibody-negative IMNM as three distinct subtypes of
      IMNM. Anti-SRP myopathy patients have more severe muscle involvement, have more
      common extra-muscular features, and may respond best to immunosuppressive
      regimens that include rituximab. In contrast, anti-HMGCR myopathy is often
      associated with statin exposure and intravenous immunoglobulin treatment may be
      an effective treatment, even as monotherapy. Both anti-SRP and anti-HMGCR
      myopathy tend to be most severe in younger patients. Furthermore, children with
      these forms of IMNM may present with dystrophy-like features which are
      potentially reversible with immunosuppressant treatment. IMNM patients with
      either autoantibody may experience fatty replacement of muscle soon after disease
      onset, suggesting that intense and early immunosuppressant therapy may provide
      the best chance to avoid long-term disability. IMNM is composed of anti-SRP
      myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM. Both anti-SRP and
      anti-HMGCR myopathy can cause severe weakness, especially in younger patients.
      Anti-SRP myopathy patients tend to have the most severe weakness and most
      prevalent extra-muscular features. Autoantibody-negative IMNM remains poorly
      described.

PMID- 29582189
TI  - Mesenchymal Chondrosarcoma: a Review with Emphasis on its Fusion-Driven Biology.
AB  - Mesenchymal chondrosarcoma is a rare but deadly form of chondrosarcoma that
      typically affects adolescents and young adults. While curative intent is possible
      for patients with localized disease, few options exist for patients in the
      unresectable/metastatic setting. Thus, it is imperative to understand the fusion
      driven biology of this rare malignant neoplasm so as to lead to the future
      development of better therapeutics for this disease. This manuscript will briefly
      review the clinical and pathologic features of mesenchymal chondrosarcoma
      followed by an appraisal of existing data linked to the fusions, HEY1-NCOA2 and
      IRF2BP2-CDX1, and the associated downstream pathways.

PMID- 29582190
TI  - Evaluation of efficacy of infliximab for retinal vasculitis and extraocular
      symptoms in Behcet disease.
AB  - PURPOSE: We evaluated ocular symptoms and activity of retinal vasculitis of
      Behcet disease before and after infliximab therapy, using Behcet disease ocular
      attack score 24 (BOS24) and fluorescein angiography (FA) score. We also analyzed
      the efficacy of infliximab for ocular and extraocular symptoms. STUDY DESIGN:
      Retrospective study. SUBJECT AND METHODS: Using medical records, we analyzed FA
      and BOS24 to evaluate the association between the efficacy of infliximab therapy
      and FA as well as BOS24 scores. Further, we evaluated the association between FA
      scores and extraocular symptoms. RESULTS: After 2 years of infliximab therapy, 6
      month BOS24 was significantly reduced compared to that before treatment (PreBOS24
      6M). After 4 years of infliximab therapy, 6-month BOS24 was also significantly
      reduced compared to preBOS24-6M. After 2 years of infliximab therapy, FA score
      median (interquartile range) decreased significantly compared to that before
      treatment [FA-2Y vs. preFA: 0 (0-0) vs.15.5 (12-24); P < 0.0001; n = 38]. The FA
      4Y score in subjects followed for at least 4 years was also significantly lower
      than the preFA score [0 (0-0) vs.16.5 (12-24.5); P < 0.0001; n = 28]. Among 38
      patients, extraocular symptoms were resolved following treatment in 29 cases
      (76.3%). No significant correlation was observed between the improvement in FA-2Y
      and FA-4Y scores and the occurrence and persistence of extraocular symptoms (P =
      0.33; n = 38 or P = 0.4; n = 28). CONCLUSION: Infliximab therapy is effective for
      the treatment of ocular and extraocular involvement of Behcet disease. BOS24 and
      FA scores are useful for evaluating the efficacy of infliximab therapy.

PMID- 29582191
TI  - Zirconia stimulates ECM-remodeling as a prerequisite to pre-osteoblast
      adhesion/proliferation by possible interference with cellular anchorage.
AB  - The biological response to zirconia (ZrO2) is not completely understood, which
      prompted us to address its effect on pre-osteoblastic cells in both direct and
      indirect manner. Our results showed that zirconia triggers important
      intracellular signaling mainly by governing survival signals which leads to cell
      adhesion and proliferation by modulating signaling cascade responsible for
      dynamic cytoskeleton rearrangement, as observed by fluorescence microscopy. The
      phosphorylations of Focal Adhesion Kinase (FAK) and Rac1 decreased in response to
      ZrO2 enriched medium. This corroborates the result of the crystal violet assay,
      which indicated a significant decrease of pre-osteoblast adhesion in responding
      to ZrO2 enriched medium. However, we credit this decrease on pre-osteoblast
      adhesion to the need to govern intracellular repertory of intracellular pathways
      involved with cell cycle progression, because we found a significant up
      phosphorylation of Mitogen-Activated Protein Kinase (MAPK)-p38 and Cyclin
      dependent kinase 2 (CDK2), while p15 (a cell cycle suppressor) decreased.
      Importantly, Protein phosphatase 2 A (PP2A) activity decreased, guaranteeing the
      significant up-phosphorylation of MAPK -p38 in response to ZrO2 enriched medium.
      Complementarily, there was a regulation of Matrix Metalloproteinases (MMPs) in
      response to Zirconia and this remodeling could affect cell phenotype by
      interfering on cell anchorage. Altogether, our results show a repertory of
      signaling molecules, which suggests that ECM remodel as a pre-requisite to pre
      osteoblast phenotype by affecting their anchoring in responding to zirconia.

PMID- 29582192
TI  - Prevalence and Risk of Polypharmacy Among Elderly Cancer Patients Receiving
      Chemotherapy in Ambulatory Oncology Setting.
AB  - PURPOSE OF REVIEW: This was a single center, retrospective cross-sectional study
      looking into the incidence and types of drug-related problems (DRPs) detected
      among elderly cancer patients receiving at least three long-term medications
      concurrent with IV chemotherapy, and the types of intervention taken to address
      these DRPs. This paper serves to elucidate the prevalence and risk of
      polypharmacy in our geriatric oncology population in an ambulatory care setting,
      to raise awareness on this growing issue and to encourage more resource
      allocation to address this healthcare phenomenon. RECENT FINDINGS: DRP was
      detected in 77.6% of elderly cancer patients receiving at least three long-term
      medications concurrent with IV chemotherapy, with an average incidence of three
      DRPs per patient. Approximately half of DRPs were related to long-term
      medications. Forty percent of DRPs required interventions at the prescriber
      level. The use of five or more medications was shown to almost double the risk of
      DRP occurrence (OR 1.862, P = 0.039). Out of the eight predefined categories of
      DRPs, underprescribing was the most common (26.7%), followed by adverse drug
      reaction (25.0%) and drug non-adherence (16.2%). Polypharmacy leading to DRPs is
      a common occurrence in elderly cancer patients receiving outpatient IV
      chemotherapy. There should be systematic measures in place to identify patients
      who are at greater risk of inappropriate polypharmacy and DRPs, and hence more
      frequent drug therapy optimization and monitoring. The identification of DRPs is
      an important step to circumvent serious drug-related harm. Future healthcare
      interventions directed at reducing DRPs should aim to assess the clinical and
      economic impact of such interventions.

PMID- 29582193
TI  - Streptomyces urticae sp. nov., isolated from rhizosphere soil of Urtica urens L.
AB  - Two novel Gram-stain positive, spore-forming, aerobic actinomycetes, designated
      NEAU-PCY-1T and NEAU-PCY-2, were isolated from rhizosphere soil of Urtica urens
      L. collected from Anshan, Liaoning Province, northeast China. The 16S rRNA gene
      sequence analysis showed that strains NEAU-PCY-1T and NEAU-PCY-2 exhibited 99.8%
      similarity with each other and are closely related to Streptomyces abietis DSM
      42080T (98.2, 98.3%) and Streptomyces fildesensis DSM 41987T (98.0, 98.1%).
      Phylogenetic analysis based on the 16S rRNA gene sequences indicated that the two
      strains formed a cluster with these two closely related species. Moreover, DNA
      DNA hybridization results and some phenotypic, physiological and biochemical
      properties differentiated the two strains from their close relatives in the genus
      Streptomyces. Based on a polyphasic taxonomy study, strains NEAU-PCY-1T and NEAU
      PCY-2 are considered to represent a novel species of the genus Streptomyces, for
      which the name Streptomyces urticae sp. nov. is proposed, with NEAU-PCY-1T (= DSM
      105115T = CCTCC AA 2017015T) as the type strain.

PMID- 29582194
TI  - Clinical Practice Guidelines for Fertility Preservation in Pediatric, Adolescent,
      and Young Adults with Cancer.
AB  - In recent years, more cancer patients are achieving long-term survival owing to
      advances in treatment. However, cancer treatment can cause gonadal dysfunction
      that leads to loss of fertility. Thus, it is important for clinical oncologists
      to consider fertility preservation in children, adolescents, and young adults
      with cancer who are expected to have a favorable outcome and may wish to have
      children in the future. Sometimes, fertility preservation has to be abandoned
      depending on the stage of the cancer and the general condition of the patient,
      because fertility preservation procedures may unacceptably delay cancer treatment
      or be too risky for the patient. The Clinical Practice Guidelines for Fertility
      Preservation in Children, Adolescents, and Young Adults with Cancer were
      published in 2017 as the first guidelines for this field in Japan. These
      guidelines cover general principles and recommendations for 8 oncological
      categories, which is a point of difference from other guidelines. Close
      coordination between clinical oncologists and reproductive medicine specialists
      is important over the long term from the pretreatment phase through the post
      treatment phase. Therefore, the guidelines were devised to help medical staff
      consider the available fertility preservation therapies and determine whether
      performing fertility preservation is appropriate before initiating the treatment
      for cancer, and to ultimately improve survivorship for children, adolescents, and
      young adults with cancer. This article reviews the latest information concerning
      clinical practice guidelines around the world, including the American Society of
      Clinical Oncology guidelines that were the first to be published in this field.

PMID- 29582195
TI  - Patterns of Family and Intimate Partner Violence in Problem Gamblers.
AB  - While the evidence about the statistical co-occurrence of family violence and
      problem gambling is growing, the mechanism by which the two behaviours are
      related is less clear. This study sought to clarify the dynamics of the problem
      behaviours, including the role of gender in victimisation and perpetration of
      violence in the family. Two-hundred-and-twelve treatment seeking problem gamblers
      (50.5% females) were recruited for interviews about past year FV and IPV
      experiences. The interviews included questions about the types of FV and IPV
      using the HITS tool (Sherin et al. in Fam Med Kans City 30:508-512, 1998). The
      questions addressed multiple family members, the temporal order of violence and
      gambling and the perceived associations between the two behaviours. The result
      show that well over half (60.8%; 95 CI = 54.1-67.2) of the participants reported
      some form of violence in the past 12 months, with no gender differences in
      relation to perpetration and victimisation. Bidirectional violence (43.9%; 95 CI
      = 37.4-50.6) was significantly more common than 'perpetration only' (11.3%; 95 CI
      = 7.7-16.3) or 'victimisation only' (5.7%; 95 CI = 3.3-9.6). Violence was mostly
      verbal, although considerable rates of physical violence also featured in the
      responses. 'Participants' own gambling preceded violence in a majority of the
      interviews but a small group of IPV victims reported that being a victim had led
      to their problematic gambling. These results can be used inform prevention,
      better treatment matching and capacity building in family violence and problem
      gambling services, where a significant focus should be on situational IPV.

PMID- 29582196
TI  - Pregnancy Outcomes Following Exposure to Quinolone Antibiotics - a Systematic
      Review and Meta-Analysis.
AB  - PURPOSE: Quinolones, and the fluoroquinolones subgroup, are a class of
      antibiotics commonly used for the treatment of a wide variety of infections.
      However, their safety profile in pregnant women is controversial. The association
      between fluoroquinolones and arthropathy was primarily described in immature
      animals, and only rarely in humans, yet it has led to the restricted use of
      quinolones during pregnancy. We aimed to assess their safety during pregnancy.
      METHODS: A systematic review and meta-analysis assessing the safety of quinolone
      exposure during any time of pregnancy, and during first trimester alone, was
      performed. The systematic review was performed using MEDLINE and EMBASE, and
      followed the PRISMA guidelines. Pooled effect sizes with corresponding 95%
      confidence intervals (CI) were calculated using random effects models, comparing
      fetal outcomes of quinolone exposed and non-exposed pregnancies. Only cohort and
      case control studies were included in the meta-analysis. RESULT: Twelve studies
      met the inclusion criteria. Exposure to quinolones during first trimester was not
      associated with an increased risk for birth defects (pooled odds ratio (OR) =
      0.89, 95% CI 0.72-1.09, I2 = 0%), stillbirth (OR = 1.32, 95% CI 0.33-5.34, I2 =
      16%), preterm birth (OR = 1.10, 95% CI 0.83-1.48, I2 = 41%) and low birth weight
      (OR = 1.29, 95% CI 0.54-3.12, I2 = 67%). CONCLUSION: The use of quinolones during
      the first-trimester of pregnancy was not associated with an increased risk of
      birth defects, stillbirths, preterm births or low birth weight. STUDY REGISTRY:
      PROSPERO CRD42017060573.

PMID- 29582197
TI  - Reduce the Sensitivity of CL-20 by Improving Thermal Conductivity Through Carbon
      Nanomaterials.
AB  - The graphene (rGO) and carbon nanotube (CNT) were adopted to enhance the thermal
      conductivity of CL-20-based composites as conductive fillers. The microstructure
      features were characterized using scanning electron microscopy (SEM) and X-ray
      diffraction (XRD), and tested the properties by differential scanning calorimeter
      (DSC), static electricity accumulation, special height, thermal conductivity, and
      detonation velocity. The results showed that the mixture of rGO and CNT had
      better effect in thermal conductivity than rGO or CNT alone under the same
      loading (1 wt%) and it formed a three-dimensional heat-conducting network
      structure to improve the heat property of the system. Besides, the linear fit
      proved that the thermal conductivity of the CL-20-based composites were
      negatively correlated with the impact sensitivity, which also explained that the
      impact sensitivity was significantly reduced after the thermal conductivity
      increased and the explosive still maintained better energy.

PMID- 29582198
TI  - Molecular dynamics simulations of inverse patchy colloids.
AB  - Inverse patchy colloids are patchy particles with differently charged surface
      regions. In this paper we focus on inverse patchy colloids with two different
      polar patches and an oppositely charged equatorial belt, and we describe a model
      and a reliable and efficient numerical algorithm that can be applied to
      investigate the properties of these particles in molecular dynamics simulations.

PMID- 29582199
TI  - Integrated Bio-behavioral Approach to Improve Adherence to Pre-exposure
      Prophylaxis and Reduce HIV Risk in People Who Use Drugs: A Pilot Feasibility
      Study.
AB  - This study reports the feasibility, acceptability, and preliminary efficacy of
      the bio-behavioral community-friendly health recovery program-an integrated, HIV
      prevention intervention to improve pre-exposure prophylaxis (PrEP) adherence and
      HIV-risk reduction behaviors among high-risk people who use drugs. We used a
      within-subjects, pretest-posttest follow-up design to recruit participants, who
      were HIV-uninfected, methadone-maintained and reported HIV-risk behaviors and had
      initiated PrEP (n = 40; males: 55%). Participants were assessed at baseline (T0),
      immediately post-intervention (4 weeks: T4) and 4 weeks post-intervention (T8).
      Immediately after completing the four weekly intervention groups, participants
      underwent a post-intervention assessment including in-depth qualitative
      interviews. Feasibility was high, assessed by participant willingness to enroll
      (90.1%) and retention (95%). Results showed that participants were highly
      satisfied and perceived the intervention as valuable and acceptable [mean: 81.3
      (range 0-100)]. Significant enhancements in self-reported PrEP adherence [F(2,74)
      = 7.500, p = 0.001] and PrEP-related knowledge [F(2,74) = 3.828, p = 0.026] were
      observed. Drug-related (e.g., injection of drugs, sharing of injection equipment)
      and sex-related (e.g., number of sexual partners, condomless sex) risk behaviors
      were reduced, while information, motivation, and behavioral skills (IMB)
      constructs increased. The results support feasibility and high acceptability and
      support further examination of the efficacy of this combination bio-behavioral
      intervention in a prospective clinical trial.

PMID- 29582200
TI  - Pig testis extract augments adiponectin expression and secretion through the
      peroxisome proliferator-activated receptor signaling pathway in 3T3-L1
      adipocytes.
AB  - Adiponectin is a key molecule whose upregulation may ameliorate symptoms of type
      2 diabetes mellitus and disorders of lipid metabolism. Several plant-derived
      components have been shown to enhance adiponectin secretion; however, there have
      been no reports on the effects of animal-derived products. Therefore, in the
      current study, we investigated whether hot-water extracts of specific livestock
      by-products induce the expression of adiponectin in mouse 3T3-L1 adipocytes. Out
      of the 11 extracts tested, pig testis extract (PTE) was found to enhance
      adiponectin expression and secretion by 3T3-L1 cells. Furthermore, simultaneous
      treatment with PTE and daidzein, a soy phytoestrogen, synergistically enhanced
      adiponectin secretion. Moreover, pretreatment with an estrogen receptor beta
      antagonist (PHTPP) diminished adiponectin secretion from daidzein-treated cells
      but not from PTE-treated cells. Transcriptome analyses revealed that both
      daidzein and PTE regulate the peroxisome proliferator-activated receptor
      signaling pathway, although differences in the regulation of gene expression were
      observed between PTE- and daidzein-treated cells. These results suggest that PTE
      ameliorates lipid metabolic dysfunction by promoting adipocyte differentiation
      and enhancing adiponectin secretion via a mechanism different from that of
      daidzein.

PMID- 29582201
TI  - Friedelane, isolated from Pouzolzia indica Gaud. exhibits toxic effect against
      melanoma.
AB  - Melanoma is a predominant cause of skin cancer-related deaths. It was reported
      that, the methanolic extract of Pouzolzia Indica (P. indica) on chromatography
      gave five compounds (1-hentriacontanyl palmitate, myricyl alcohol, 6,7
      dimethoxycoumarin, trichadonic acid and friedelane), which inhibited the acute
      promyelocytic leukemia cell lines, NB4, and HT93A. Friedelane was extracted as
      active compound from methanolic extract of P. indica. In this study, friedelane
      was tested on murine metastatic B16F10 and B16BL6 melanoma cell lines. To achieve
      the target, the cell viability using trypan blue exclusion, acridine orange/EtBr
      staining and cell cytotoxicity were tested using MTT assay. Caspase-3, caspase-9,
      Cyt-c, BAD and Bax protein were assayed to evidence the apoptosis induction. The
      compound friedelane shows potent cytotoxic effect against metastatic melanoma
      mouse cell lines in 10 ug/ml concentration.

PMID- 29582202
TI  - Automated quantitative image analysis for ex vivo metastasis assays reveals
      differing lung composition requirements for metastasis suppression by KISS1.
AB  - Imaging is broadly used in biomedical research, but signal variation complicates
      automated analysis. Using the Pulmonary Metastasis Assay (PuMA) to study
      metastatic colonization by the metastasis suppressor KISS1, we cultured GFP
      expressing melanoma cells in living mouse lung ex vivo for 3 weeks.
      Epifluorescence images of cells were used to measure growth, creating large
      datasets which were time consuming and challenging to quantify manually due to
      scattering of light from outside the focal plane. To address these challenges, we
      developed an automated workflow to standardize the measurement of disseminated
      cancer cell growth by applying statistical quality control to remove unanalyzable
      images followed and a filtering algorithm to quantify only in-focus cells. Using
      this tool, we demonstrate that expression of the metastasis suppressor KISS1 does
      not suppress growth of melanoma cells in the PuMA, in contrast to the robust
      suppression of lung metastasis observed in vivo. This result may suggest that a
      factor required for metastasis suppression is present in vivo but absent in the
      PuMA, or that KISS1 suppresses lung metastasis at a step in the metastatic
      cascade not tested by the PuMA. Together, these data provide a new tool for
      quantification of metastasis assays and further insight into the mechanism of
      KISS1 mediated metastasis suppression in the lung.

PMID- 29582203
TI  - Prevalence and Types of Anemia in a Large Refugee Cohort in Western Europe in
      2015.
AB  - Currently, vast numbers of migrants with largely unknown health statuses have
      been entering Europe. To improve care taking strategies, prevalence, severity and
      types of anemia in a large refugee cohort were assessed. Blood counts were
      performed in n = 787 inhabitants from six German refugee centers. Most included
      migrants were young, male adults. Anemia was present in 22.5% of subjects with an
      age-dependent prevalence increase (7.9% > 18 years vs. 30.8% > 50 years). More
      females than males were anemic (27.1% vs. 20.4%). The majority of affected
      migrants had mild anemia (86.2%) of either normocytic/normochromic (55.9%) or
      microcytic/hypochromic (20.9%) type. Observed anemia frequencies are in
      accordance with global anemia prevalence recently estimated by the WHO. However,
      the observed high rates of anemia particularly in female and older refugees
      emphasize the need for adapted care taking strategies in refugee medicine.
      Further evaluation of causes of anemia in the migrating population is needed.

PMID- 29582204
TI  - GABAergic Mechanism of Anticonvulsive Effect of Chemical Agent RU-1205.
AB  - The study examined the effect of 9-(2-morpholinoethyl)-2-(4
      fluorophenyl)imidazo[1,2-alpha] benzimidazole dihydrochloride (RU-1205) on the
      latency of seizures provoked by corazol, bicuculline, or picrotoxin. This agent
      (10 and 20 mg/kg) increased the seizure latency in the experimental models of
      epileptogenesis. The blockers of GABAA and GABA A -rho receptors picrotoxin and
      (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, respectively, were
      employed to study the effects of RU-1205 on electrical activity of somatosensory
      cortical neurons and on formation of pathological rhythms in the rat brain. RU
      1205 inhibited the focal background rhythm and eliminated the epileptiform
      activity, which can be mediated by interaction with GABAA receptors.

PMID- 29582205
TI  - In Vitro Model for Studying of the Role of IGFBP6 Gene in Breast Cancer
      Metastasizing.
AB  - IGFBP6 gene plays an important role in the pathogenesis of breast cancer. In this
      work, we performed knockdown of IGFBP6 gene in MDA-MB-231 cells and obtained a
      stable cell line. Knockdown of IGFBP6 gene was confirmed by the real-time PCR.
      The influence of IGFBP6 gene on migration and proliferation of breast cancer
      cells was studied. Knockdown of IGFBP6 gene reduced migration activity of MDA-MB
      231 cells and increased their proliferation rate. This in vitro cell model can be
      used for the further analysis of the role of IGFBP6 gene in the pathogenesis of
      breast cancer.

PMID- 29582206
TI  - Parental and Child Psychopathology: Moderated Mediation by Gender and Parent
      Child Relationship Quality.
AB  - Previous literature has not examined the processes underlying the relations among
      parent-child relationship quality, parental psychopathology, and child
      psychopathology in the context of gender. Further, research examining these
      variables in emerging adulthood is lacking. The current study examined whether
      parent-child relationship quality would mediate the relation between parental and
      child psychopathology, and whether gender moderated these associations.
      Participants were emerging adults (N = 665) who reported on perceptions of their
      parents' and their own psychological problems as well as their parent-child
      relationship quality. Results indicated that the relation between parental
      internalizing problems and parent-child relationship quality was positive for
      males, and that mother-child relationship quality was related positively to
      psychological problems in males. This suggests that sons may grow closer to their
      parents (particularly their mother) who are exhibiting internalizing problems; in
      turn, this enmeshed relationship may facilitate transmission of psychopathology.
      Mediational paths were conditional upon gender, suggesting moderated mediation.
      Overall, the current study emphasizes that the complexities of parenting must be
      understood in the context of gender. Further, the mother-son dyad may
      particularly warrant further attention.

PMID- 29582207
TI  - Concurrent Versus Sequential Chemoradiation Therapy in Completely Resected
      Pathologic N2 Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the
      National Cancer Data Base.

PMID- 29582209
TI  - Long-term exposure to TNF-alpha leads human skin fibroblasts to a p38 MAPK- and
      ROS-mediated premature senescence.
AB  - Tumor necrosis factor alpha (TNF-alpha) is an inflammatory mediator overexpressed
      in the skin as a response to ultraviolet radiation, as well as in chronic non
      healing wounds. On the other hand, senescent fibroblasts have been shown to
      accumulate in the skin under these stressful conditions. Accordingly, here we
      assessed the putative implication of TNF-alpha in the induction of premature
      senescence of human adult dermal fibroblasts. We showed that TNF-alpha led to a
      rapid transient p38 MAPK activation, while elevation of reactive oxygen species
      (ROS) only occurred after a chronic exposure to TNF-alpha. Furthermore, in
      contrast to the majority of previous reports using various cell models and
      experimental settings, it was a long-term treatment with TNF-alpha that resulted
      in the premature senescence of human dermal fibroblasts, as shown by the reduced
      proliferative potential and the increased senescence associated beta
      galactosidase staining of the cells. TNF-alpha-senescent cells displayed a
      permanent phosphorylation of p38 MAPK and an inflammatory and catabolic
      phenotype. Increased ROS levels were also observed, possibly attributed to the
      weakened anti-oxidative response evidenced by the underexpression of the Nrf2
      regulated genes encoding HO-1 and NQO1. These traits and the overall senescent
      phenotype were significantly reversed using the known anti-oxidant N-acetyl-L
      cysteine or a specific p38 MAPK inhibitor, suggesting the participation of
      oxidative stress and of the p38 MAPK pathway in TNF-alpha-triggered premature
      senescence. Even more, the observed blockade of ROS accumulation in senescent
      skin fibroblasts by p38 MAPK inhibition indicates a possible link between these
      two separate events during the manifestation of TNF-alpha-induced senescence.

PMID- 29582208
TI  - Update on Bile Acid Malabsorption: Finally Ready for Prime Time?
AB  - PURPOSE OF REVIEW: To provide an update on the prevalence, pathophysiology,
      disease associations, and treatment options for bile acid malabsorption (BAM).
      RECENT FINDINGS: *Molecular mechanisms-BAs prevent water reabsorption and
      increase water secretion by intracellular mediators, increasing aquaporin
      channels and intracellular permeability. *Inflammatory bowel disease-new
      molecular mechanisms of BAM are identified in patients without ileal disease,
      including changes in expression of ileal BA transporter and nuclear receptors
      involved in BA homeostasis. *Microscopic colitis-BAM is one of the mechanisms
      leading to microscopic colitis. *Diagnostic testing-new diagnostic tests have
      been launched in the USA (serum C4 and fecal 48-h BA excretion); stimulated FGF19
      has higher detection of BAM compared to fasting sample alone. *Treatment
      investigational FXR agonists may provide a daily, oral option for treatment of
      BAM instead of BA sequestrants. There is a greater appreciation of the biological
      role of bile acids across multiple fields of medicine, including gastrointestinal
      indications.

PMID- 29582210
TI  - In-hospital and day-120 survival of critically ill solid cancer patients after
      discharge of the intensive care units: results of a retrospective multicenter
      study-A Groupe de recherche respiratoire en reanimation en Onco-Hematologie (Grrr
      OH) study.
AB  - OBJECTIVES: To assess outcomes at hospital discharge and day-120 after intensive
      care unit (ICU) discharge among patients with solid cancer admitted to ICU and to
      identify characteristics associated with in-hospital and day-120 after ICU
      discharge mortalities. DESIGN: International, multicenter, retrospective study.
      SETTING: Five ICUs in France and Brazil, two located in cancer centers, two in
      university affiliated and one in general hospitals. PATIENTS: Consecutive
      patients aged > 18 years, with underlying solid cancers (known before admission
      to the ICU or diagnosed during the stay in the ICU), admitted to the
      participating ICUs and discharged alive from the ICU from January 2006 to
      December 2011 were included in this study. Patients admitted after scheduled
      surgery or to secure procedure were excluded. Variables of interest were in
      hospital and day-120 post-ICU mortality among patients discharged alive from the
      ICU. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A total of 1053 patients aged
      63 years (54-71) (median [IQR]) were included. Most of the patients were of the
      male gender (66.8%). The in-ICU, in-hospital, and four-month post-ICU discharge
      mortalities were, respectively, 41.3, 60.7, and 65.8%. Among patients discharged
      alive from the ICU, in multivariate analysis, factors associated with four months
      post-ICU discharge mortality were type of cancer (OR from 0.25 to 0.52 when
      compared to lung cancers), systemic extension of the disease (OR 2.54; 95% CI
      1.87-3.45), need for invasive mechanical ventilation (OR 2.54; 95% CI 1.80-3.59),
      for vasopressors (OR 2.35; 95% CI 1.66-3.29), or renal replacement therapy (OR
      1.54; 95% CI 0.99-2.38). A predictive score, "Oncoscore," was built performing
      fairly in predicting 4 months post-ICU discharge outcome (AUC 0.74; 95% CI 0.71
      0.77). CONCLUSION: Despite the high day-120 mortality following the ICU
      discharge, our study reports a meaningful medium-term survival rate after the ICU
      discharge of solid cancer patients. Of utmost importance, the "Oncoscore" must be
      validated in prospective studies and cannot be used, in its form without external
      validation, for individual decision making. Prospective studies to answer
      questions not provided by this study are needed, including only patients with
      solid cancers admitted in the ICU for medical reasons or after emergency surgery.

PMID- 29582211
TI  - The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK
      Pathway.
AB  - PURPOSE: Protecting the heart from ischaemia-reperfusion (IR) injury is a major
      goal in patients presenting with an acute myocardial infarction. Pyroptosis is a
      novel form of cell death in which caspase 1 is activated and cleaves interleukin
      1beta. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also
      clinically available. It has been shown to be protective against acute IR in vivo
      rat model, and therefore might be a promising possibility for future
      cardioprotective therapy. However, it is not known whether protection by VX-765
      involves the reperfusion injury salvage kinase (RISK) pathway. We therefore
      investigated whether VX-765 protects the isolated, perfused rat heart via the
      PI3K/Akt pathway and whether protection was additive with ischaemic
      preconditioning (IPC). METHODS: Langendorff-perfused rat hearts were subject to
      ischaemia and reperfusion injury in the presence of 30 MUM VX-765, with precedent
      IPC, or the combination of VX-765 and IPC. RESULTS: VX-765 reduced infarct size
      (28 vs 48% control; P < 0.05) to a similar extent as IPC (30%; P < 0.05). The PI3
      kinase inhibitor, wortmannin, abolished the protective effect of VX-765.
      Importantly in the model used, we were unable to show additive protection with VX
      765 + IPC. CONCLUSIONS: The caspase 1 inhibitor, VX-765, was able to reduce
      myocardial infarction in a model of IR injury. However, the addition of IPC did
      not demonstrate any further protection.

PMID- 29582212
TI  - Evaluation of potential antiplatelet effects of CSL112 (Apolipoprotein A-I
      [Human]) in patients with atherosclerosis: results from a phase 2a study.
AB  - CSL112 (Apolipoprotein A-I [Human]), an infusible, plasma-derived apolipoprotein
      A-I, is being developed to reduce cardiovascular events following acute
      myocardial infarction (AMI). A predecessor compound (CSL111) demonstrated a
      potential antiplatelet effect. A phase 2a multicentre, randomised, single
      ascending dose study in patients with stable atherosclerotic disease receiving
      dual antiplatelet therapy (DAPT) assessed the potential additive effects of
      CSL112 administration on platelet function and increase bleeding risk in the
      subacute period after AMI. Patients (n = 44) on aspirin (75-325 mg/day) and
      either clopidogrel (75 mg/day, n = 37) or prasugrel (10 mg/day, n = 7) for > 30
      days alongside standard-of-care therapy were randomised to a single dose of
      placebo or CSL112: 1.7, 3.4, or 6.8 g. Light transmission aggregometry was used
      to assess platelet aggregation in response to 2 mM arachidonic acid, 5 and 20 uM
      adenosine diphosphate, and 4 ug/mL collagen, pre-dose (baseline) and up to 48 h
      post-dosing. Compared to placebo, CSL112 had no clinically meaningful time- or
      dose-dependent effects on maximum platelet aggregation in response to any
      agonist, by either dose or renal function subgroup (p > 0.05). Coagulation
      parameters showed little variation over time or between treatment groups (p >
      0.05). CSL112, when co-administered with standard DAPT, did not significantly
      influence platelet aggregation in response to agonists and is, therefore, not
      expected to significantly increase bleeding risk when administered with
      antiplatelet therapies.

PMID- 29582213
TI  - Management of antithrombotic therapy in adults with immune thrombocytopenia
      (ITP): a survey of ITP specialists and general hematologist-oncologists.
AB  - While patients with immune thrombocytopenia (ITP) and low platelet counts are at
      risk for bleeding, they are not protected against arterial and venous thrombotic
      events. Frequently, hematologists are asked to consult on a patient with ITP
      requiring an antiplatelet (AP) agent or anticoagulant (AC). No direct evidence
      exists to guide hematologists in weighing the risk of thrombosis against the risk
      of bleeding in patients with ITP. Therefore, we performed a survey to determine
      the preferred management of AP/AC therapy in ITP patients. The survey described
      hypothetical patient scenarios and asked respondents to recommend a minimum
      platelet count for initiation of AP/AC therapy. We surveyed both hematologists
      with an international reputation in treatment of ITP (n = 48) and also general
      hematologist-oncologists in Oklahoma (n = 97). Response rates were 38/48 (79%)
      for the ITP specialists and 46/97 (47%) for general hematologist-oncologists.
      Overall, recommended platelet thresholds for antithrombotic therapy were similar
      between ITP specialists and general hematologist-oncologists. Although both
      groups recommended a minimum platelet count of 50 * 109/L for AP and AC therapy
      in most scenarios, there was great variability in individual practice patterns
      among respondents. This study highlights the need for studies of patients with
      ITP who require AP/AC therapy to provide high-quality evidence for establishing
      optimal management strategies.

PMID- 29582214
TI  - The effect of gramicidin inclusions on the local order of membrane components.
AB  - We study the local effect of the antimicrobial peptide Gramicidin A on bilayers
      composed of lipids or surfactants using nuclear magnetic resonance spectroscopy
      and wide-angle X-ray scattering, techniques that probe the orientational and
      positional order of the alkyl chains, respectively. The two types of order vary
      with temperature and peptide concentration in complex ways which depend on the
      membrane composition, highlighting the subtlety of the interaction between
      inclusions and the host bilayer. The amplitude of the variation is relatively
      low, indicating that the macroscopic constants used to describe the elasticity of
      the bilayer are unlikely to change with the addition of peptide.

PMID- 29582215
TI  - Correction to: Predictors of Participation in the Family Check-Up Program: a
      Randomized Trial of Yearly Services from Age 2 to 10 Years.
AB  - The original version of this article contained a mistake: The affiliations 1, 4
      for author Thomas J. Dishion are incorrect and should be corrected to 2, 4.

PMID- 29582216
TI  - Commentary on Participation in Preventive Interventions.
AB  - In this commentary on the special issue, Preventive Parenting Interventions:
      Advancing Conceptualizations and Enhancing Reach, operationalization of
      participation, who engages in prevention interventions, and common themes from
      the studies are discussed. The papers in the special issue illustrate the
      importance of studying factors that increase participation in prevention and
      point out the need for additional research to understand these factors. These
      papers highlight the diverse conceptualizations of participation as well as a
      need to move toward standardization of methods to assess related constructs.
      Research is needed to elucidate the potential of enhanced participation and
      engagement in interventions to meaningfully impact intervention outcomes and
      ultimately improve the population-level benefit attributable to prevention
      efforts. Prevention scientists should attend to factors influencing participation
      in prevention as early in the intervention research process as possible in order
      to increase the likelihood that the target population will utilize evidence-based
      prevention interventions in real-world settings, under real-world conditions.

PMID- 29582217
TI  - Electrically Conductive TPU Nanofibrous Composite with High Stretchability for
      Flexible Strain Sensor.
AB  - Highly stretchable and electrically conductive thermoplastic polyurethane (TPU)
      nanofibrous composite based on electrospinning for flexible strain sensor and
      stretchable conductor has been fabricated via in situ polymerization of
      polyaniline (PANI) on TPU nanofibrous membrane. The PANI/TPU membrane-based
      sensor could detect a strain from 0 to 160% with fast response and excellent
      stability. Meanwhile, the TPU composite has good stability and durability.
      Besides, the composite could be adapted to various non-flat working environments
      and could maintain opportune conductivity at different operating temperatures.
      This work provides an easy operating and low-cost method to fabricate highly
      stretchable and electrically conductive nanofibrous membrane, which could be
      applied to detect quick and tiny human actions.

PMID- 29582218
TI  - Current Concepts in the Treatment of Resectable Pancreatic Cancer.
AB  - PURPOSE OF REVIEW: The diagnosis of pancreatic cancer carries with it a high
      mortality rate. Despite advances in the field, this has remained relatively
      unchanged over the last few decades. Current options for the treatment of
      resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction
      with the historical data that support them. We will focus on updates in treatment
      guidelines and ongoing clinical trials of interest. RECENT FINDINGS: For
      localized disease, standard of care includes resection followed by adjuvant
      chemotherapy +/- chemoradiation. Recently, a report was published supporting the
      use of doublet therapy with gemcitabine and capecitabine (as opposed to
      gemcitabine monotherapy), which prompted a practice-changing update to major
      treatment guidelines. Multiple trials using neoadjuvant treatment, novel
      therapies, and different forms of radiation are ongoing. Although pancreatic
      cancer is an active area of research, outcomes remain dismal. Clinical trials
      will need to be more robust and innovative to drastically improve survival
      statistics.

PMID- 29582219
TI  - Scientific output quality of 40 globally top-ranked medical researchers in the
      field of osteoporosis.
AB  - : The study presents the research output of 40 globally top-ranked authors,
      publishing in the field of osteoporosis. Their h-index is compared with the
      Scientific Quality Index (SQI), a novel indicator. Using SQI, 92.5% of the
      authors changed their initial positions in the general ranking. SQI partially
      depends on bibliometric measures different from those influencing h-index and may
      be considered as an assessment tool, reflecting more objective, qualitative,
      rather than quantitative, features of individual scientific output. PURPOSE: The
      study approaches the research output of 40 globally top-ranked authors in the
      field of osteoporosis. METHODS: The assessed authors were identified in the
      Scopus database, using the key word "osteoporosis" and the h-index data,
      collected during the last decade (2008-2017). The data, concerning the scientific
      output, expressed by the h-index, were compared with a novel indicator of
      scientific quality-called the Scientific Quality Index (SQI). SQI is calculated
      according to the following formula: Parameter No. 1 + Parameter No. 2, where:
      Parameter No. 1 (the percent of papers cited >= 10 times) the number of papers
      cited >= 10 times (excluding self-citations and citations of all co-authors) is
      divided by the number of all the published papers (including the papers with no
      citation) * 100%, Parameter No. 2 (the mean number of citations per paper) the
      total number of citations (excluding self-citations and citations of all co
      authors) divided by the number of all published papers (including papers with no
      citation). RESULTS: The following research output values were obtained: the
      citation index, 2483.6 +/- 1348.7; the total number of papers, 75.1 +/- 23.2; the
      total number of cited papers, 69.3 +/- 22.0; the number of papers cited, at
      least, 10 times, 45.4 +/- 17.2; the percent of papers cited, at least, 10 times,
      59.9 +/- 10.0; and the mean citations per paper, 32.8 +/- 15.0. The mean value of
      Hirsch index was 24.2 +/- 6.2 and SQI 92.7 +/- 22.3. Using SQI, only three
      authors did not change their initial ranking position, established according to
      the h-index; 18 authors noted a decrease, while other 19 improved their initial
      ranking position. The h-index correlated with SQI; r = 0.72; p < 0.0001.
      CONCLUSION: Qualitative features of scientific output, reflected by SQI, have
      changed the classification of 92.5% of authors. SQI may be considered as an
      assessment tool which is more strongly determined by qualitative than
      quantitative features of individual scientific output.

PMID- 29582220
TI  - Assessing False-Belief Understanding in Children with Autism Using a Computer
      Application: A Pilot Study.
AB  - We have developed a False-Belief (FB) understanding task for use on a computer
      tablet, trying to assess FB understanding in a less social way. It is based on
      classical FB protocols, and additionally includes a manipulation of language in
      an attempt to explore the facilitating effect of linguistic support during FB
      processing. Specifically, the FB task was presented in three auditory conditions:
      narrative, silent, and interference. The task was assumed to shed new light on
      the FB difficulties often observed in Autism Spectrum Disorder (ASD). Sixty-eight
      children with ASD (M = 7.5 years) and an age matched comparison group with 98
      typically developing (TD) children were assessed with the FB task. The children
      with ASD did not perform above chance level in any condition, and significant
      differences in success rates were found between the groups in two conditions
      (silent and narrative), with TD children performing better. We discuss
      implications, limitations, and further developments.

PMID- 29582221
TI  - The Influence of Learning Style on English Learning Achievement Among
      Undergraduates in Mainland China.
AB  - Learning style is one of the main factors that determines how students learn
      English and has a significant influence on students' learning strategy selection,
      which further affects their learning outcomes (Ehrman and Oxford in Mod Lang J
      74(3):311-327, 1990; Oxford in Language learning styles and strategies: an
      overview, 2003. http://web.ntpu.edu.tw/~language/workshop/read2.pdf ). This study
      examines the learning style preferences of Chinese university students and
      whether those preferences influence their English achievements. Four hundred
      undergraduates from one university in eastern mainland China participated in this
      study. Data from 329 valid questionnaires were analysed. The results revealed
      that the Chinese university students preferred the visual learning style the
      most, followed by the auditory and kinaesthetic styles. However, no learning
      style preference was found to influence the students' English proficiency.
      Cultural reasons are discussed to explain the findings, which contradict those of
      previous studies of learning style theories and practices. This study recommends
      that Chinese scholars consider issues of English teaching and learning in China
      and to adopt appropriate teaching methods to effectively improve English
      teaching.

PMID- 29582222
TI  - Pre-analytical Factors Influence Accuracy of Urine Spot Iodine Assessment in
      Epidemiological Surveys.
AB  - Urinary iodine concentration (UIC) is commonly used to assess iodine status of
      subjects in epidemiological surveys. As pre-analytical factors are an important
      source of measurement error and studies about this phase are scarce, our
      objective was to assess the influence of urine sampling conditions on UIC, i.e.,
      whether the child ate breakfast or not, urine void rank of the day, and time span
      between last meal and urine collection. A nationwide, two-stage, stratified,
      cross-sectional study including 1560 children (6-12 years) was performed in 2012.
      UIC was determined by the Sandell-Kolthoff method. Pre-analytical factors were
      assessed from children's mothers by using a questionnaire. Association between
      iodine status and pre-analytical factors were adjusted for one another and socio
      economic characteristics by multivariate linear and multinomial regression models
      (RPR: relative prevalence ratios). Skipping breakfast prior to morning urine
      sampling decreased UIC by 40 to 50 MUg/L and the proportion of UIC < 100 MUg/L
      was higher among children having those skipped breakfast (RPR = 3.2[1.0-10.4]).
      In unadjusted analyses, UIC was less among children sampled more than 5 h from
      their last meal. UIC decreased with rank of urine void (e.g., first vs. second, P
      < 0.001); also, the proportion of UIC < 100 MUg/L was greater among 4th rank
      samples (vs. second RPR = 2.1[1.1-4.0]). Subjects' breakfast status and urine
      void rank should be accounted for when assessing iodine status. Providing
      recommendations to standardize pre-analytical factors is a key step toward
      improving accuracy and comparability of survey results for assessing iodine
      status from spot urine samples. These recommendations have to be evaluated by
      future research.

PMID- 29582223
TI  - Abstracts from the Joint Meeting of the International Society for NeuroVirology
      (ISNV) and the Society on NeuroImmune Pharmacology (SNIP) April 10-14, 2018,
      Chicago, Illinois, USA.

PMID- 29582224
TI  - Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data
      from the RAMoss Study.
AB  - BACKGROUND: Ramucirumab-alone or combined with paclitaxel-represents one of the
      main options for patients failing first-line treatment for advanced gastric
      cancer. OBJECTIVE: The RAMoss study aimed to evaluate the safety and efficacy
      profile of ramucirumab in the "real-life setting". PATIENTS AND METHODS: Patients
      from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v.
      d1,15q28 with or without paclitaxel 80 mg/m2 i.v. d1,8,15q28. The primary
      endpoint was safety, and secondary endpoints were overall response rate (ORR),
      progression-free survival (PFS), and overall survival (OS). RESULTS: One hundred
      sixty-seven patients with disease progression on first-line therapy received
      ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median
      treatment duration was 4 months (1-17 months). Global incidence of grade (G) 3-4
      toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to
      toxicity in 3% of patients. The most frequent adverse events (AE) were G1-2
      fatigue (27.5%), G1-2 neuropathy (26.3%), and G1-2 neutropenia (14.9%). ORR was
      20.2%. Stable disease was observed in 39.2% of patients, with a disease control
      rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months
      (95% confidence interval [CI] 4.1-4.7), whereas median OS was 8.0 months (95% CI:
      7.09-8.9). In a multivariate analysis, ECOG performance status <1 or >=1 (HR
      1.13, 95% CI 1.0-1.27, p = 0.04) and the presence versus absence of peritoneal
      metastases (HR 1.57, 95% CI 1.63-2.39, p = 0.03) were independent poor prognostic
      factors. CONCLUSIONS: These "real-life" efficacy data on ramucirumab treatment
      are in line with previous randomized trials. Ramucirumab is well tolerated in
      daily clinical practice.

PMID- 29582225
TI  - Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super
      Refractory Status Epilepticus.
AB  - BACKGROUND: Functional neurologic outcome for children with refractory and super
      refractory status epilepticus has not been well defined. METHODS: Retrospective
      chart review including children age 0-17 years who received pentobarbital
      infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms
      of mortality, need for new medical technology assistance at hospital discharge
      and functional neurologic outcome determined by pediatric cerebral performance
      category score (PCPC). Potential patient characteristics associated with
      functional neurologic outcome including age, sex, ethnicity, etiology of the
      status epilepticus, and duration of pentobarbital infusion were evaluated.
      RESULTS: Forty children met inclusion criteria. In-hospital mortality was 30%
      (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28)
      declined in function >= 2 PCPC categories at hospital discharge. 25% (7/28) of
      survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures
      persisted at discharge for most patients with new onset status epilepticus while
      the majority of patients with known epilepsy returned to baseline seizure
      frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy
      (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase
      in PCPC score >= 2 categories in univariable analysis. Duration of pentobarbital
      infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in
      patients who demonstrated significant decline in neurologic function. None of
      these variables maintained statistical significance when multiple logistic
      regression model adjusting for PCPC score at admission was applied. At long-term
      follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to
      discharge and 23% (5/22) showed deterioration including three additional deaths.
      CONCLUSIONS: Mortality in this population was high. The majority of children
      experienced some degree of disability at discharge. Despite prolonged
      pentobarbital infusion, there were cases of survival with good neurologic
      outcome.

PMID- 29582226
TI  - A long term feed supplementation based on phosphate binders in Feline Chronic
      Kidney Disease.
AB  - Chronic kidney disease (CKD) is a very common disorder in elderly cats. A proper
      renal diet represents the most efficient therapeutic intervention to improve
      survival and life quality in feline patients with 3 and 4 International Renal
      Interest Society (IRIS) stages. Twenty cats were selected in this study. Ten were
      administered the dietary supplementation for 360 days and the other ten, whose
      owners did not give consent for any supplemental therapies apart from the renal
      diet, were selected from a clinical database and used as control group. The
      present study is a long term study (360 days) aiming to evaluate the efficacy and
      palatability of a dietary supplementation containing calcium carbonate, calcium
      lactate gluconate, chitosan and sodium bicarbonate in cats diagnosed with 3 and 4
      IRIS stages of CKD. The owners were asked to fill in questionnaires to get
      information on the cat's appetite, the palatability of the given supplement, the
      presence of vomit and/or diarrhoea, general health and vitality. Hematochemical,
      biochemical and urinary analyses were performed on day 0, 30, 60, 90, 120,
      150,180 and 360. GraphPad Prism(r) software was used to perform statistical
      analysis. Our study shows that the given dietary supplement reduced serum
      phosphorus and increased serum bicarbonate values in cats with CKD. In turn, this
      supplement could be used as a support therapy in cats with advanced CKD improving
      their clinical conditions without any adverse reaction. Finally, it is important
      to underline that all the animals completed the study and the owners reported a
      good palatability of the feed supplement.

PMID- 29582227
TI  - Structure and function of photosystem I in Cyanidioschyzon merolae.
AB  - The evolution of photosynthesis from primitive photosynthetic bacteria to higher
      plants has been driven by the need to adapt to a wide range of environmental
      conditions. The red alga Cyanidioschyzon merolae is a primitive organism, which
      is capable of performing photosynthesis in extreme acidic and hot environments.
      The study of its photosynthetic machinery may provide new insight on the
      evolutionary path of photosynthesis and on light harvesting and its regulation in
      eukaryotes. With that aim, the structural and functional properties of the PSI
      complex were investigated by biochemical characterization, mass spectrometry, and
      X-ray crystallography. PSI was purified from cells grown at 25 and 42  degrees C,
      crystallized and its crystal structure was solved at 4 A resolution. The
      structure of C. merolae reveals a core complex with a crescent-shaped structure,
      formed by antenna proteins. In addition, the structural model shows the position
      of PsaO and PsaM. PsaG and PsaH are present in plant complex and are missing from
      the C. merolae model as expected. This paper sheds new light onto the evolution
      of photosynthesis, which gives a strong indication for the chimerical properties
      of red algae PSI. The subunit composition of the PSI core from C. merolae and its
      associated light-harvesting antennae suggests that it is an evolutionary and
      functional intermediate between cyanobacteria and plants.

PMID- 29582228
TI  - Using PhotoVoice to Promote Land Conservation and Indigenous Well-Being in
      Oklahoma.
AB  - Indigenous ancestral teachings commonly present individual and community health
      as dependent upon relationships between human and nonhuman worlds. But how do
      persons conversant with ancestral teachings effectively convey such perspectives
      in contemporary contexts, and to what extent does the general tribal citizenry
      share them? Can media technology provide knowledge keepers with opportunities to
      communicate their perspectives to larger audiences? What are the implications for
      tribal citizens' knowledge and views about tribal land use policies? Using a
      PhotoVoice approach, we collaborated with a formally constituted body of Cherokee
      elders who supply cultural guidance to the Cherokee Nation government in
      Oklahoma. We compiled photographs taken by the elders and conducted interviews
      with them centered on the project themes of land and health. We then developed a
      still-image documentary highlighting these themes and surveyed 84 Cherokee
      citizens before and after they viewed it. Results from the pre-survey revealed
      areas where citizens' perspectives on tribal policy did not converge with the
      elders' perspectives; however, the post-survey showed statistically significant
      changes. We conclude that PhotoVoice is an effective method to communicate
      elders' perspectives, and that tribal citizens' values about tribal land use may
      change as they encounter these perspectives in such novel formats.

PMID- 29582229
TI  - In-silico guided discovery of novel CCR9 antagonists.
AB  - Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel
      disease, including ulcerative colitis and Crohn's disease. There is limited
      experimental data on CCR9 and its ligands, complicating efforts to identify new
      small molecule antagonists. We present here results of a successful virtual
      screening and rational hit-to-lead campaign that led to the discovery and initial
      optimization of novel CCR9 antagonists. This work uses a novel data fusion
      strategy to integrate the output of multiple computational tools, such as 2D
      similarity search, shape similarity, pharmacophore searching, and molecular
      docking, as well as the identification and incorporation of privileged chemokine
      fragments. The application of various ranking strategies, which combined
      consensus and parallel selection methods to achieve a balance of enrichment and
      novelty, resulted in 198 virtual screening hits in total, with an overall hit
      rate of 18%. Several hits were developed into early leads through targeted
      synthesis and purchase of analogs.

PMID- 29582230
TI  - Binding free energy calculations to rationalize the interactions of huprines with
      acetylcholinesterase.
AB  - In the present study, the binding free energy of a family of huprines with
      acetylcholinesterase (AChE) is calculated by means of the free energy
      perturbation method, based on hybrid quantum mechanics and molecular mechanics
      potentials. Binding free energy calculations and the analysis of the geometrical
      parameters highlight the importance of the stereochemistry of huprines in AChE
      inhibition. Binding isotope effects are calculated to unravel the interactions
      between ligands and the gorge of AChE. New chemical insights are provided to
      explain and rationalize the experimental results. A good correlation with the
      experimental data is found for a family of inhibitors with moderate differences
      in the enzyme affinity. The analysis of the geometrical parameters and
      interaction energy per residue reveals that Asp72, Glu199, and His440 contribute
      significantly to the network of interactions between active site residues, which
      stabilize the inhibitors in the gorge. It seems that a cooperative effect of the
      residues of the gorge determines the affinity of the enzyme for these inhibitors,
      where Asp72, Glu199, and His440 make a prominent contribution.

PMID- 29582231
TI  - Amino acid substitutions in low pathogenic avian influenza virus strains isolated
      from wild birds in Korea.
AB  - Wild birds are natural hosts and reservoirs for influenza A viruses. However,
      many species, such as many waterfowl, are asymptomatic when infected and so
      facilitate the generation of viral genetic diversity. Mutations of key genes
      affect the replicability, pathogenicity, transmissibility, and antiviral
      resistance of influenza A viruses. In this study, we isolated avian influenza
      (AI) viruses from wild bird fecal samples and analyzed changes in amino acids
      over time and geographic region to monitor the biological change of the AI virus.
      Between 2014 and 2016, we collected 38,921 fresh fecal samples from major wild
      bird habitats located throughout Korea and isolated 123 AI viruses. We
      subsequently selected 22 amino acid sites to analyze for changes. These sites
      included ten sites associated with replication, ten sites associated with
      pathogenicity, three sites associated with transmission, and seven sites
      associated with antiviral resistance. We found substitution rates of 71.7% at the
      C38Y amino acid site within the polymerase basic protein 1 (PB1) gene, 66.7% at
      the D222G site within the hemagglutinin (HA) 1 gene, and 75.6% at the A184 site
      within the nucleoprotein (NP) gene. Alterations of the PB1, HA1, and NP genes are
      closely associated with increased pathogenicity in chickens and mammals. The
      remaining sites of interest exhibited few modifications. In this study, we
      confirmed that AI viruses circulating among wild birds in Korea consistently
      exhibit modifications at amino acid sites linked with replication and
      pathogenicity.

PMID- 29582232
TI  - Challenges to Effective Primary Care-Specialty Communication and Coordination in
      the Mental Health Referral and Care Process for Publicly Insured Children.
AB  - Publicly insured children needing referral to mental health (MH) services often
      do not access or receive services. The objective of this study was to identify
      gaps in communication and coordination between primary care providers (PCPs) and
      MH providers during the MH referral and care process for publicly insured
      children. Thirteen semi-structured interviews were conducted with 10 PCPs and
      staff from a federally qualified health center (FQHC) and 6 MH providers and
      staff from two local MH clinics. Interview participants identified multiple gaps
      in communication throughout the care process and different phases as priorities
      for improvement. PCPs described primary care-MH communication challenges during
      early phases, while MH providers described coordination challenges in
      transferring patients back to primary care for ongoing mental health management.
      Strategies are needed to improve primary care-specialty MH communication and
      coordination throughout all phases of the referral and care process, particularly
      at initial referral and transfer back to primary care.

PMID- 29582233
TI  - Economic Evaluation of the Juvenile Drug Court/Reclaiming Futures (JDC/RF) Model.
AB  - Juvenile drug court (JDC) programs are an increasingly popular option for
      rehabilitating juvenile offenders with substance problems, but research has found
      inconsistent evidence regarding their effectiveness and economic impact. While
      assessing client outcomes such as reduced substance use and delinquency is
      necessary to gauge program effectiveness, a more comprehensive understanding of
      program success and sustainability can be attained by examining program costs and
      economic benefits. As part of the National Cross-Site Evaluation of JDC and
      Reclaiming Futures (RF), an economic analysis of five JDC/RF programs was
      conducted from a multisystem and multiagency perspective. The study highlights
      the direct and indirect costs of JDC/RF and the savings generated from reduced
      health problems, illegal activity, and missed school days. Results include the
      average (per participant) cost of JDC/RF, the total economic benefits per JDC/RF
      participant, and the net savings of JDC/RF relative to standard JDC.

PMID- 29582234
TI  - An Evaluation of the Implementation of the Australian ATAPS Suicide Prevention
      Services Initiative.
AB  - The Access to Allied Psychological Services (ATAPS) Suicide Prevention Services
      initiative is an Australian Government-funded primary mental healthcare
      initiative providing free intensive psychological intervention for consumers at
      moderate risk of self-harm or suicide. Findings from a multi-method evaluation
      aimed at identifying whether the initiative is being implemented as stipulated
      within the operational guidelines, barriers and facilitators to implementation,
      and preliminary outcomes suggest that the Suicide Prevention Services are largely
      being implemented as stipulated in the Guidelines, but with some exceptions. In
      particular, service delivery barriers unique to rural and remote areas place
      limitations on implementation. Uptake of the ATAPS Suicide Prevention Services is
      high (10,428 consumers were referred to the Suicide Prevention Services between
      October 2008 and April 2013, and 86% of those attended at least one session), as
      is acceptance from organizations involved in its implementation.

PMID- 29582235
TI  - Characterization of isolated liver sinusoidal endothelial cells for liver
      bioengineering.
AB  - BACKGROUND: The liver sinusoidal capillaries play a pivotal role in liver
      regeneration, suggesting they may be beneficial in liver bioengineering. This
      study isolated mouse liver sinusoidal endothelial cells (LSECs) and determined
      their ability to form capillary networks in vitro and in vivo for liver tissue
      engineering purposes. METHODS AND RESULTS: In vitro LSECs were isolated from
      adult C57BL/6 mouse livers. Immunofluorescence labelling indicated they were LYVE
      1+/CD32b+/FactorVIII+/CD31-. Scanning electron microscopy of LSECs revealed the
      presence of characteristic sieve plates at 2 days. LSECs formed tubes and sprouts
      in the tubulogenesis assay, similar to human microvascular endothelial cells
      (HMEC); and formed capillaries with lumens when implanted in a porous collagen
      scaffold in vitro. LSECs were able to form spheroids, and in the spheroid gel
      sandwich assay produced significantly increased numbers (p = 0.0011) of capillary
      like sprouts at 24 h compared to HMEC spheroids. Supernatant from LSEC spheroids
      demonstrated significantly greater levels of vascular endothelial growth factor-A
      and C (VEGF-A, VEGF-C) and hepatocyte growth factor (HGF) compared to LSEC
      monolayers (p = 0.0167; p = 0.0017; and p < 0.0001, respectively), at 2 days,
      which was maintained to 4 days for HGF (p = 0.0017) and VEGF-A (p = 0.0051). In
      vivo isolated mouse LSECs were prepared as single cell suspensions of 500,000
      cells, or as spheroids of 5000 cells (100 spheroids) and implanted in SCID mouse
      bilateral vascularized tissue engineering chambers for 2 weeks.
      Immunohistochemistry identified implanted LSECs forming LYVE-1+/CD31- vessels. In
      LSEC implanted constructs, overall lymphatic vessel growth was increased (not
      significantly), whilst host-derived CD31+ blood vessel growth increased
      significantly (p = 0.0127) compared to non-implanted controls. LSEC labelled with
      the fluorescent tag DiI prior to implantation formed capillaries in vivo and
      maintained LYVE-1 and CD32b markers to 2 weeks. CONCLUSION: Isolated mouse LSECs
      express a panel of vascular-related cell markers and demonstrate substantial
      vascular capillary-forming ability in vitro and in vivo. Their production of
      liver growth factors VEGF-A, VEGF-C and HGF enable these cells to exert a growth
      stimulus post-transplantation on the in vivo host-derived capillary bed,
      reinforcing their pro-regenerative capabilities for liver tissue engineering
      studies.

PMID- 29582236
TI  - Gastrointestinal Hemorrhage in Left Ventricular Assist Device Patients: Red Scare
      or Pressure from the Right?

PMID- 29582237
TI  - Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in
      Patients on Warfarin or Dabigatran.
AB  - BACKGROUND AND AIM: Different oral anticoagulants may be associated with
      gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We
      aimed to test this hypothesis. METHODS: Two blinded gastroenterologists
      independently analyzed source documents from the randomized evaluation of long
      term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150),
      dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation
      (NVAF). RESULTS: Major GIB events (total n = 546) and life-threatening GIB events
      (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR
      1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR
      1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was
      similarly rare across treatment groups. Lower GI major bleeding and life
      threatening bleeding were more common with D150 compared to warfarin (RR 2.23
      [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to
      warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from
      colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01
      for both dose comparisons). Subacute and chronic MGIB events were more common
      with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45],
      respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72
      [1.20, 2.47], respectively). CONCLUSIONS: In a chronic NVAF population, D150 but
      not D110 is associated with increased major and life-threatening GI bleeding in
      comparison with warfarin. At both dabigatran doses, increased bleeding from the
      colorectum, in particular from angiodysplasia, is seen.

PMID- 29582238
TI  - Influence of tube potential on quantitative coronary plaque analyses by low
      radiation dose computed tomography: a phantom study.
AB  - Previous studies have shown that employing the low dose computed tomography (CT)
      technique based on low tube potential reduces the radiation dose required for the
      coronary artery examination protocol. However, low tube potential may adversely
      influence the CT number of plaque composition. Therefore, we aimed to determine
      whether quantitative atherosclerotic plaque analysis by a multi-slice, low
      radiation dose CT protocol using 80 kilovolts (kV) yields results comparable to
      those of the standard 120 kV protocol. Artificial plaque samples (n = 17)
      composed of three kinds of plaque were scanned at 120 and 80 kV. Relative low
      density and medium-density plaque component volumes obtained by three protocols
      (80 kV, 60 Hounsfield units [HU] threshold; 120 kV, 60 HU threshold; and 80 kV,
      82 HU threshold) were compared. Using the 60 HU threshold, relative volume of the
      low-density plaque component obtained at 80 kV was lower than that obtained at
      120 kV (27 +/- 3% vs. 51 +/- 5%, P < 0.001), whereas relative volume of the
      medium-density plaque component obtained at 80 kV was higher than that obtained
      at 120 kV (73 +/- 3% vs. 48 +/- 5%, P < 0.001). By contrast, no significant
      difference in relative volume obtained at 80 kV (82 HU threshold) versus 120 kV
      (60 HU threshold) was observed for either low-density (52 +/- 5% vs. 51 +/- 5%)
      or medium-density (48 +/- 5% vs. 48 +/- 5%) plaque component. Low tube potential
      may affect the accuracy of quantitative atherosclerotic plaque analysis. For our
      phantom test, 82 HU was the optimal threshold for scanning at 80 kV.

PMID- 29582239
TI  - Effects of a novel curcumin derivative on the functions of kidney in
      streptozotocin-induced type 2 diabetic rats.
AB  - OBJECTIVE: B6, an analog of curcumin, is a compound isolated from a traditional
      Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6
      on diabetic nephropathy and the related mechanisms. MATERIALS AND METHODS: The
      effects of B6 were studied on fast-blood glucose, serum creatinine, urea
      nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of
      ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin.
      RESULTS: The results showed that B6 treatment could reduce serum creatinine, urea
      nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal
      pathological changes in diabetic rats and increase the levels of ACE2 and ACE2
      mRNA. CONCLUSION: These results suggested B6 could protect the renal function of
      diabetic rats. This study provided scientific basis for the further researches
      and clinical applications of B6.

PMID- 29582240
TI  - Enhancement of drug permeability across blood brain barrier using nanoparticles
      in meningitis.
AB  - The central nervous system, one of the most delicate microenvironments of the
      body, is protected by the blood-brain barrier regulating its homeostasis. Blood
      brain barrier is a highly complex structure that tightly regulates the movement
      of ions of a limited number of small molecules and of an even more restricted
      number of macromolecules from the blood to the brain, protecting it from injuries
      and diseases. However, the blood-brain barrier also significantly precludes the
      delivery of drugs to the brain, thus, preventing the therapy of a number of
      neurological disorders. As a consequence, several strategies are currently being
      sought after to enhance the delivery of drugs across the blood-brain barrier.
      Within this review a brief description of the structural and physiological
      features of the barriers and the recently born strategy of brain drug delivery
      based on the use of nanoparticles are described. Finally, the future
      technological approaches are described. The strong efforts to allow the
      translation from preclinical to concrete clinical applications are worth the
      economic investments.

PMID- 29582242
TI  - Automatic Pectoral Muscle Region Segmentation in Mammograms Using Genetic
      Algorithm and Morphological Selection.
AB  - In computer-aided diagnosis systems for breast mammography, the pectoral muscle
      region can easily cause a high false positive rate and misdiagnosis due to its
      similar texture and low contrast with breast parenchyma. Pectoral muscle region
      segmentation is a crucial pre-processing step to identify lesions, and accurate
      segmentation in poor-contrast mammograms is still a challenging task. In order to
      tackle this problem, a novel method is proposed to automatically segment pectoral
      muscle region in this paper. The proposed method combines genetic algorithm and
      morphological selection algorithm, incorporating four steps: pre-processing,
      genetic algorithm, morphological selection, and polynomial curve fitting. For the
      evaluation results on different databases, the proposed method achieves average
      FP rate and FN rate of 2.03 and 6.90% (mini MIAS), 1.60 and 4.03% (DDSM), and
      2.42 and 13.61% (INBreast), respectively. The results can be comparable
      performance in various metrics over the state-of-the-art methods.

PMID- 29582243
TI  - Monte Carlo simulations for dose enhancement in cancer treatment using bismuth
      oxide nanoparticles implanted in brain soft tissue.
AB  - The objective of this work is to study the dosimetric performances of bismuth
      oxide nanoparticles implanted in tumors in cancer radiotherapy. GEANT4 based
      Monte Carlo numerical simulations were performed to assess dose enhancement
      distributions in and around a 1 * 1 * 1 cm3 tumor implanted with different
      concentrations of bismuth oxide and irradiated with low energies 125I, 131Cs, and
      103Pd radioactive sources. Dose contributions were considered from
      photoelectrons, Auger electrons, and characteristic X-rays. Our results show the
      dose enhancement increased with increasing both bismuth oxide concentration in
      the target and photon energy. A dose enhancement factor up to 18.55 was obtained
      for a concentration of 70 mg/g of bismuth oxide in the tumor when irradiated with
      131Cs source. This study showed that bismuth oxide nanoparticles are innovative
      agents that could be potentially applicable to in vivo cancer radiotherapy due to
      the fact that they induce a highly localized energy deposition within the tumor.

PMID- 29582241
TI  - Redox cofactor engineering in industrial microorganisms: strategies, recent
      applications and future directions.
AB  - NAD and NADP, a pivotal class of cofactors, which function as essential electron
      donors or acceptors in all biological organisms, drive considerable catabolic and
      anabolic reactions. Furthermore, they play critical roles in maintaining
      intracellular redox homeostasis. However, many metabolic engineering efforts in
      industrial microorganisms towards modification or introduction of metabolic
      pathways, especially those involving consumption, generation or transformation of
      NAD/NADP, often induce fluctuations in redox state, which dramatically impede
      cellular metabolism, resulting in decreased growth performance and biosynthetic
      capacity. Here, we comprehensively review the cofactor engineering strategies for
      solving the problematic redox imbalance in metabolism modification, as well as
      their features, suitabilities and recent applications. Some representative
      examples of in vitro biocatalysis are also described. In addition, we briefly
      discuss how tools and methods from the field of synthetic biology can be applied
      for cofactor engineering. Finally, future directions and challenges for
      development of cofactor redox engineering are presented.

PMID- 29582244
TI  - A Comparison of Five Algorithms for Fetal Magnetocardiography Signal Extraction.
AB  - Fetal magnetocardiography (fMCG) provides accurate and reliable measurements of
      electrophysiological events in the fetal heart and is capable of studying fetuses
      with congenital heart diseases. A variety of techniques exist to extract the fMCG
      signal with the demand for non-invasively obtained fetal cardiac information. To
      the best of our knowledge, there is no comparative study published in the field
      as to how the various extraction algorithms perform. We perform a comparative
      study of the ability of five methods to extract the fMCG using real biomagnetic
      signals, two of those methods are applied to real fMCG data for the first time.
      Biomagnetic signals were recorded and processed with each of the five methods to
      obtain fMCG. The R peaks of the fMCG traces were obtained via a peak-detection
      algorithm. From whole recording for each method, the fetal heart rate (FHR) was
      calculated and used to perform FHR variability (FHRV) analysis. Additionally, we
      calculated durations from the PQRST complex from time-averaged data during sinus
      rhythm. The five methods recovered the fMCG signals, but two of them were able to
      extract cleaner fMCG and the morphology was observed from the continuous data.
      The time-averaged data showed very similar morphologies between methods, but two
      of them displayed a signal amplitude reduction on the R-waves and T-waves. Values
      of PQRST durations, FHR and FHRV were in the range of previous fetal cardiac
      studies. We have compared five methods for fMCG extraction and showed their
      ability to perform fMCG analysis.

PMID- 29582245
TI  - Quantum Calculations on Plant Cell Wall Component Interactions.
AB  - Density functional theory calculations were performed to assess the relative
      interaction energies of plant cell wall components: cellulose, xylan, lignin and
      pectin. Monomeric and tetramer linear molecules were allowed to interact in four
      different configurations for each pair of compounds. The M05-2X exchange
      correlation functional which implicitly accounts for short- and mid-range
      dispersion was compared against MP2 and RI-MP2 to assess the reliability of the
      former for modeling van der Waals forces between these PCW components. Solvation
      effects were examined by modeling the interactions in the gas phase, in explicit
      H2O, and in polarized continuum models (PCM) of solvation. PCMs were used to
      represent water, methanol, and chloroform. The results predict the relative
      ranges of each type of interaction and when specific configurations will be
      strongly preferred. Structures and energies are useful as a basis for testing
      classical force fields and as guidance for coarse-grained models of PCWs.

PMID- 29582246
TI  - Current Treatment Patterns Among Postmenopausal Women with HR+/HER2- Metastatic
      Breast Cancer in US Community Oncology Practices: An Observational Study.
AB  - INTRODUCTION: Recent approval of novel agents has changed the treatment landscape
      for post menopausal women with hormone receptor-positive (HR+) and human
      epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer
      (mBC). The objective of this study was to describe contemporary treatment
      patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting.
      METHODS: Data were collected from 64 community oncologists in the US between
      February and June 2017 using an online medical records extraction tool.
      Physicians reviewed medical records and provided information on patient
      demographics and disease characteristics, and treatment regimens. Treatment
      patterns were described overall and separately by line of therapy and type of
      treatment received. Discontinuation rates were estimated using Kaplan-Meier
      analyses to account for censoring. RESULTS: Data were collected on 401 patients.
      Mean age at the time of mBC diagnosis was 67 years. In the first-line setting,
      52.4% of patients received a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based
      regimen, most commonly with an aromatase inhibitor (AI) (39.2%) or fulvestrant
      (10.0%); 30.2% received endocrine therapy, most commonly an AI (21.4%) or
      fulvestrant (5.2%) in monotherapy, while 12.7% received a chemotherapy-based
      regimen. In the second-line setting, 42.9% of patients received a CDK4/6
      inhibitor-based regimen, 18.4% received endocrine therapy, and 22.4% received a
      chemotherapy-based regimen. The 18-month discontinuation rate was 34.5% for
      patients receiving a CDK4/6 inhibitor-based regimen and 45.8% for patients
      receiving endocrine monotherapy. CONCLUSION: CDK4/6 inhibitor-based regimens were
      the most commonly prescribed treatment in both first- and second-line settings. A
      wide variety of treatment sequences were observed which suggests an absence of a
      standard of care for postmenopausal women with HR+/HER2- mBC in real-world
      practice.

PMID- 29582248
TI  - Safety and Pharmacokinetics of DS-8500a, a Novel GPR119 Agonist, After Multiple
      Oral Doses in Healthy Japanese Males.
AB  - BACKGROUND AND OBJECTIVES: G protein-coupled receptor 119 (GPR119) agonists
      reduce plasma glucose by promoting insulin secretion in a glucose-dependent
      manner. We evaluated the safety and pharmacokinetics of multiple oral doses of DS
      8500a, a GPR119 agonist, under fed conditions in healthy adult Japanese male
      subjects. METHODS: In this Phase 1, randomized, placebo-controlled, double-blind,
      multiple oral dose study, participants were aged >= 20 and <= 45 years with a
      body mass index >= 18.5 and < 25.0 kg/m2. DS-8500a 50 and 100 mg or placebo were
      administered orally, once daily, 30 min after breakfast for 7 days. The primary
      endpoints were pharmacokinetics and safety. RESULTS: Twenty-four subjects were
      included (6, 9, and 9 in the placebo, 50-, and 100-mg groups, respectively). On
      Day 7, the mean maximum plasma concentration (Cmax) was 812 ng/mL in the 50-mg
      group and 1310 ng/mL in the 100-mg group. The mean area under the plasma
      concentration-time curve during dosing interval (AUCtau) was 7910 and 13,200
      ng.h/mL in the two treatment groups, respectively. The observed accumulation
      ratio was 1.25 in the 50-mg group and 1.32 in the 100-mg group. All adverse
      events were mild and judged unrelated to the study drug. CONCLUSIONS: DS-8500a
      plasma concentrations reached steady state from Day 3, and Cmax and AUCtau
      increased in a less than dose-proportional manner. After repeated doses of DS
      8500a at 100 mg, the DS-8500a trough concentration was expected to reach a
      pharmacologically active dose. DS-8500a was well tolerated up to 100 mg after a 7
      day administration. STUDY REGISTRY IDENTIFICATION: JAPIC ID: JapicCTI-173550
      (registered retrospectively on 30 March 2017).

PMID- 29582247
TI  - TaEDS1 genes positively regulate resistance to powdery mildew in wheat.
AB  - KEY MESSAGE: Three EDS1 genes were cloned from common wheat and were demonstrated
      to positively regulate resistance to powdery mildew in wheat. The EDS1 proteins
      play important roles in plant basal resistance and TIR-NB-LRR protein-triggered
      resistance in dicots. Until now, there have been very few studies on EDS1 in
      monocots, and none in wheat. Here, we report on three common wheat orthologous
      genes of EDS1 family (TaEDS1-5A, 5B and 5D) and their function in powdery mildew
      resistance. Comparisons of these genes with their orthologs in diploid ancestors
      revealed that EDS1 is a conserved gene family in Triticeae. The cDNA sequence
      similarity among the three TaEDS1 genes was greater than 96.5%, and they shared
      sequence similarities of more than 99.6% with the respective orthologs from
      diploid ancestors. The phylogenetic analysis revealed that the EDS1 family
      originated prior to the differentiation of monocots and dicots, and EDS1 members
      have since undergone clear structural differentiation. The transcriptional levels
      of TaEDS1 genes in the leaves were obviously higher than those of the other
      organs, and they were induced by Blumeria graminis f. sp. tritici (Bgt) infection
      and salicylic acid (SA) treatment. The BSMV-VIGS experiments indicated that knock
      down the transcriptional levels of the TaEDS1 genes in a powdery mildew-resistant
      variety of common wheat compromised resistance. Contrarily, transient
      overexpression of TaEDS1 genes in a susceptible common wheat variety
      significantly reduced the haustorium index and attenuated the growth of Bgt.
      Furthermore, the expression of TaEDS1 genes in the Arabidopsis mutant eds1-1
      complemented its susceptible phenotype to powdery mildew. The above evidences
      strongly suggest that TaEDS1 acts as a positive regulator and confers resistance
      against powdery mildew in common wheat.

PMID- 29582249
TI  - Fluticasone Propionate/Salmeterol MDPI (AirDuo RespiClick(r)): A Review in
      Asthma.
AB  - The novel, easy-to-use, breath-actuated fluticasone propionate/salmeterol
      multidose dry powder inhaler (MDPI) (AirDuo RespiClick(r)) was recently approved
      in the USA for twice-daily treatment of asthma in patients aged >= 12 years. This
      inhaled corticosteroid (ICS) and long-acting beta2-adrenoreceptor agonist (LABA)
      combination treatment is available in low-, mid- and high-dosage formulations
      (55/14, 113/14 and 232/14 MUg, respectively). In 12-week, phase III trials in
      patients aged >= 12 years with persistent asthma, all three dosages of
      fluticasone propionate/salmeterol MDPI treatment produced significant
      improvements in lung function and other asthma symptoms compared with fluticasone
      propionate MDPI monotherapy or placebo MDPI. In a 26-week, phase III trial in
      this patient population, mid- and high-dosage fluticasone propionate/salmeterol
      MDPI were noninferior to mid- (250/50 MUg) and high- (500/50 MUg) dosage
      fluticasone propionate/salmeterol DPI (Advair Diskus(r)), respectively, in terms
      of improvements in lung function. Treatment-emergent adverse events (TEAEs) with
      fluticasone propionate/salmeterol MDPI were mostly of mild to moderate severity,
      with no severe TEAEs deemed to be treatment related. Although long-term
      pharmacovigilance is required to fully establish its safety, given the ease of
      use and favorable characteristics of the device and its clinical efficacy at
      relatively low metered doses of the active moieties, fluticasone
      propionate/salmeterol MDPI is an important emerging treatment option in patients
      aged >= 12 years with asthma.

PMID- 29582251
TI  - Up-Regulation of Akt and Nav1.8 in BmK I-Induced Pain.

PMID- 29582252
TI  - Safety and efficacy of alternate-day corticosteroid treatment as adjunctive
      therapy for rheumatoid arthritis: a comparative study.
AB  - Corticosteroids (CSs), used to treat rheumatoid arthritis (RA), confer a risk of
      adverse events (AEs). This study investigated the safety and efficacy of
      alternate-day (QOD) CS therapy for RA. All patients (> 18 years) who started oral
      CS therapy for RA, between 2005 and 2014, at our hospital were retrospectively
      analysed. The patients were divided into the daily (QD) and QOD CS therapy groups
      to investigate the rates of CS-related major AEs (infection, diabetes,
      hypertension, cardiovascular events and fragility fractures) within the first
      year of treatment. The number of patients free from CS treatment at 1 year and
      the mean decreases in C-reactive protein (CRP) levels at 1 month were also
      investigated. In total, 138 patients were analysed (QD group, 68; QOD group, 70).
      The maximum daily CS dose was not significantly different between the two groups,
      but the annual cumulative dose was significantly lower in the QOD group (P <
      0.01). The infection rate was significantly lower in the QOD group (24.3%) than
      in the QD group (50.0%; P < 0.01), whereas the other AE rates were similar
      between the groups. The CS-free rate at 1 year was significantly higher in the
      QOD group (58.6%) than in the QD group (26.5%; P < 0.01). The mean CRP decreases
      over 1 month of CS therapy were not significantly different between the groups.
      QOD CS treatment leads to a lower infection rate and less CS dependence than does
      daily treatment; both RA treatments are equally effective.

PMID- 29582253
TI  - Development of a droplet digital PCR assay for population analysis of
      aflatoxigenic and atoxigenic Aspergillus flavus mixtures in soil.
AB  - Aflatoxin B1 is a potent hepatotoxin and carcinogen that poses a serious safety
      hazard to both humans and animals. Aspergillus flavus is the most common
      aflatoxin-producing species on corn, cotton, peanuts, and tree nuts. Application
      of atoxigenic strains to compete against aflatoxigenic strains of A. flavus has
      emerged as one of the most practical strategies for ameliorating aflatoxin
      contamination in food. Genes directly involved in aflatoxin biosynthesis are
      clustered on an 82-kb region of the genome. Three atoxigenic strains (CA12, M34,
      and AF123) were each paired with each of four aflatoxigenic strains (CA28, CA42,
      CA90, and M52), inoculated into soil and incubated at 28  degrees C for 2 weeks
      and 1 month. TaqMan probes, omtA-FAM, and norA-HEX were designed for developing a
      droplet digital PCR (ddPCR) assay to analyze the soil population of mixtures of
      A. flavus strains. DNA was extracted from each soil sample and used for ddPCR
      assays. The data indicated that competition between atoxigenic and aflatoxigenic
      was strain dependent. Variation in competitive ability among different strains of
      A. flavus influenced the population reduction of the aflatoxigenic strain by the
      atoxigenic strain. Higher ratios of atoxigenic to aflatoxigenic strains increased
      soil population of atoxigenic strains. This is the first study to demonstrate the
      utility of ddPCR to quantify mixtures of both atoxigenic and aflatoxigenic A.
      flavus strains in soil and allows for rapid and accurate determination of
      population sizes of atoxigenic and aflatoxigenic strains. This method eliminates
      the need for isolation and identification of individual fungal isolates from
      experimental soil samples.

PMID- 29582250
TI  - Opposite Interplay Between the Canonical WNT/beta-Catenin Pathway and PPAR Gamma:
      A Potential Therapeutic Target in Gliomas.
AB  - In gliomas, the canonical Wingless/Int (WNT)/beta-catenin pathway is increased
      while peroxisome proliferator-activated receptor gamma (PPAR-gamma) is
      downregulated. The two systems act in an opposite manner. This review focuses on
      the interplay between WNT/beta-catenin signaling and PPAR-gamma and their
      metabolic implications as potential therapeutic target in gliomas. Activation of
      the WNT/beta-catenin pathway stimulates the transcription of genes involved in
      proliferation, invasion, nucleotide synthesis, tumor growth, and angiogenesis.
      Activation of PPAR-gamma agonists inhibits various signaling pathways such as the
      JAK/STAT, WNT/beta-catenin, and PI3K/Akt pathways, which reduces tumor growth,
      cell proliferation, cell invasiveness, and angiogenesis. Nonsteroidal anti
      inflammatory drugs, curcumin, antipsychotic drugs, adiponectin, and sulforaphane
      downregulate the WNT/beta-catenin pathway through the upregulation of PPAR-gamma
      and thus appear to provide an interesting therapeutic approach for gliomas.
      Temozolomide (TMZ) is an antiangiogenic agent. The downstream action of this
      opposite interplay may explain the TMZ-resistance often reported in gliomas.

PMID- 29582254
TI  - 2,4 Dinitrophenol Attenuates Mitochondrial Dysfunction and Improves
      Neurobehavioral Outcomes Postanoxia in Neonatal Rats.
AB  - Following anoxia, a rapid and marked mitochondrial-linked cell death occurs in
      the cerebral cortex of newborn rats which leads to insult advancement within a
      couple of days and causes lifelong neurobehavioral abnormalities. The present
      study investigated the role of 2,4 dinitrophenol (2,4 DNP) in three doses,
      i.e.,1, 2.5, and 5 mg/kg on anoxia-induced time-dependent mitochondrial
      dysfunction and associated neurobehavioral outcome using a well-established
      global model of anoxia. Briefly, rat pups of 30-h age (P2) were subjected to two
      episodes of anoxia (10 min each) at 24 h of the time interval in an enclosed
      chamber supplied with 100% N2 and immersed in a water bath (35-37  degrees C) to
      avoid hypothermia. Results demonstrated that the uncoupler 2,4 DNP, in the dose
      2.5 and 5 mg/kg injected i.p. within 5 min after second anoxic episode
      significantly (P < 0.05) preserved mitochondrial function on day 7 preferentially
      by maintaining mitochondrial membrane potential (MMP) and inhibiting
      mitochondrial permeability transition (MPT) pore. Further, 2,4 DNP preserved
      mitochondrial function by improving different states of mitochondrial respiration
      (s2, s3, s4, s5), respiratory control ratio (RCR), antioxidant enzyme system like
      superoxide dismutase (SOD) and catalase (CAT), and mitochondrial complex enzymes
      (I, II, IV, V) after anoxia. Furthermore, a marked decrease in the levels of
      expression of cytochrome C (cyt C) and pro-apoptotic (Bcl-2 family) and apoptotic
      (caspase-9/3) proteins was observed on day 7 indicating that the treatment with
      2,4 DNP prevented mitochondrial dysfunction and further insult progression (day 1
      to day 7). Moreover, 2,4 DNP decreased the apoptotic cell death on day 7 and
      overall improved the neurobehavioral outcomes like reflex latency and hanging
      latency which suggests its role in treating neonatal anoxia.

PMID- 29582255
TI  - Association between Job Factors, Burnout, and Preference for a New Job: a
      Nationally Representative Physician Survey.

PMID- 29582257
TI  - Measurement of extraocular horizontal muscle insertion distance via anterior
      segment optical coherence tomography of healthy children and comparison with
      healthy adults.
AB  - PURPOSE: The aim of the study was to determine the corneal limbus-extraocular
      muscle insertion distance (LID), via anterior segment optical coherence
      tomography, in healthy children and healthy adults and to compare the results of
      the measurements of the two groups. METHODS: Muscle limbus distances were
      measured using AS-OCT in 60 healthy cases in two groups. Children aged 8-13 years
      were evaluated as group 1, and healthy adults aged 25-30 years were evaluated as
      group 2. Measurements of 120 horizontal muscles were taken by one doctor (OBO).
      The values were compared according to age and gender groups, and correlation
      between LID measurements and spherical equivalent. Statistical evaluation was
      performed using SPSS 16(r) for Windows with the Student's t test and Pearson
      correlation coefficient test. RESULTS: LID measurements for MR and for lateral
      rectus (LR) were 5.74 +/- 0.75 and 6.74 +/- 1.11 mm, in the pediatric age-group,
      and 5.73 +/- 0.75 and 6.84 +/- 1.15 mm, in the adult age-group, respectively.
      There was no statistically significant difference between the two groups in terms
      of MR distances. There was a slight increase in the adult values, for the LR
      distance. There was no significant difference in terms of gender. Correlation was
      found 0.62 for MR and 0.46 for LR between LID measurements and spherical
      equivalent in the pediatric age-group. CONCLUSIONS: In healthy individuals,
      different imaging modalities can be used to measure LID, but AS-OCT can be used
      in pediatric age-groups as a preferred imaging method because it is easy and
      noninvasive.

PMID- 29582256
TI  - Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in
      juvenile hamsters induced by orally administered propionic acid and clindamycin.
AB  - Increasing evidence suggests that the gut microbiota plays a key role in the
      central nervous system (CNS), and alterations of the gut microbiota composition
      due to environmental factors can contribute to neurodevelopmental disorders.
      Animal modeling may help to identify drugs that can normalize the altered gut
      microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose
      of the present study was to investigate the therapeutic potency of probiotics
      such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a
      neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile
      hamsters. Fifty young golden Syrian hamsters weighing between 60 and 70 g were
      enrolled in the study. The hamsters were randomly divided into five groups, each
      with ten hamsters. The hamsters in the control group only received phosphate
      buffered saline orally. The PPA-treated group received a neurotoxic dose of 250
      mg PPA/kg body weight (BW)/day for three days. The clindamycin-treated group
      received 30 mg clindamycin/kg BW as a single orogastric dose on the day the
      experiment started. The two therapeutic groups received the same doses of PPA and
      clindamycin followed by 0.2 g probiotic/kg BW for three weeks. Biochemical
      parameters related to glutamate excitotoxicity were investigated in brain
      homogenates from each group of hamsters. Additionally, the development of
      pathogenic bacteria was monitored in stool samples from all groups. The
      microbiology results of the present study revealed descriptive changes in the
      fecal microbiota and the appearance of Clostridium species in the hamsters
      treated with clindamycin and PPA. Additionally, the effectiveness of the
      probiotic in the restoration of the normal gut microbiota was demonstrated.
      Moreover, clindamycin and PPA were found to induce a significant depletion of
      Mg2+ and gamma-aminobutyric acid (GABA) and a remarkable increase in the Na+/Mg2+
      and glutamate/GABA ratios but non-significant changes in the absolute levels of
      K+, Na+ and glutamate. The bacteria overgrowth induced by PPA and clindamycin in
      the present study effectively showed signs of neuronal toxicity. The study
      indicates that probiotics can be used safely to ameliorate glutamate
      excitotoxicity mostly through increasing depleted GABA and Mg2+ and decreasing
      the excitatory neurotransmitter, glutamate.

PMID- 29582258
TI  - Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia.
AB  - BACKGROUND: To report midterm outcomes of strabismus strategy for management of
      diplopia in chronic progressive external ophthalmoplegia and specific surgical
      planning rationale. DESIGN: Retrospective interventional case series. RESULTS:
      Two patients, a 26-year-old male and a 36-year-old female, diagnosed with chronic
      progressive external ophthalmoplegia presented with blepharoptosis and
      intermittent diplopia. Ocular motility examination was significant for bilateral
      profound impairment of adduction with relative preservation of abduction,
      infraduction and elevation. Control of intermittent exotropia gradually worsened
      over 3 and 1.5 years of follow-up, respectively, in the presence of documented
      stability of the angle of exodeviation. Strabismus surgery involving modest
      amounts of bilateral medial rectus resection and lateral rectus recessions was
      undertaken. Surgical intervention was successful in controlling alignment in
      primary position and alleviating diplopia and asthenopia after 9 and 8 years of
      follow-up time, respectively, despite slow progression of ophthalmoplegia.
      CONCLUSION: Bilateral selective impairment of adduction and intermittent
      exotropia may be the presenting ocular motility disturbance in chronic
      progressive external ophthalmoplegia. Properly designed strabismus surgery may
      provide sustainable, in the midterm, control of alignment and symptomatic relief
      in selected patients with CPEO.

PMID- 29582259
TI  - Corneal densitometry after accelerated corneal collagen cross-linking in
      progressive keratoconus.
AB  - PURPOSE: To analyze changes in corneal densitometry 3 months after accelerated
      corneal collagen cross-linking (CXL) measured with Scheimpflug tomography.
      METHODS: In this study we reviewed charts and anterior segment data of patients
      who had undergone accelerated pulsed epithelium-off CXL (30 mW/cm2 for 4 min, 8
      min total radiation time) for treatment of progressive keratoconus in the
      Department of Ophthalmology, Goethe University, Frankfurt, Germany. Visual,
      topographic, pachymetric and densitometric data were extracted before surgery and
      at the 3-month follow-up. Corneal densitometry measurements from different
      corneal layers and zones obtained using Scheimpflug tomography (Pentacam HR,
      Oculus). RESULTS: The study investigated 12 eyes of 12 patients. The anterior
      (120 MUm) stromal layer within the 0.0 to 2.0 mm and 2.0 to 6.0 mm concentric
      zones showed a significant elevation of mean densitometry 3 months post-surgery
      (P = 0.045; P = 0.015) compared to baseline. A mean stromal demarcation line was
      apparent at a depth of 203.00 MUm +/- 13.53 (SD). After accelerated CXL, no
      change in mean corrected distance visual acuity (LogMAR) was observed but a
      thinning of the cornea measured by a significant reduction in central pachymetry
      (MUm). CONCLUSION: Accelerated CXL results in an increase in corneal
      densitometry, particularly in the anterior stromal layer within the two central
      concentric zones (0.0 to 2.0 mm and 2.0 to 6.0 mm) of the cornea at 3 months
      postoperatively. The changes in corneal densitometry of the anterior stromal
      layer did not correlate with postoperative visual acuity or central pachymetry.

PMID- 29582260
TI  - Orbital apex syndrome secondary to optic nerve cysticercosis.
AB  - A 22-year-old male presented to us with complaints of sudden painful loss of
      vision in left eye 10 days ago along with inward deviation of the left eye. Best
      corrected visual acuity (BCVA) in right eye was 20/20 and 20/50 in left eye. Left
      eye showed limitation of abduction, a relative afferent pupillary defect, normal
      anterior segment with optic disc oedema. Contrast-enhanced MRI of the brain and
      orbit showed thickening of left optic nerve along with a cystic lesion near the
      orbital apex with a central iso- to hyperintense spot resembling a scolex. A
      diagnosis of left orbital apex syndrome secondary to optic nerve cysticercosis
      was made. Patient was treated with oral albendazole and intravenous
      corticosteroids for 3 days followed by oral corticosteroids. Ten weeks post
      treatment, his BCVA in the left eye improved to 20/20 and colour vision and
      visual fields improved. Pallor of the left optic disc was noted, and ocular
      motility improved completely. MRI after treatment showed a decreased thickness of
      left optic nerve with disappearance of the cystic lesion.

PMID- 29582261
TI  - Effects of different treatments on chemical and morphological features of eroded
      dentin.
AB  - To evaluate the treatment of eroded dentin (Sensodyne Repair & ProtectTM, Er:YAG
      laser and combinations). The occlusal surfaces of 25 third molars were sectioned
      1.5 mm in thickness. After an erosion cycle (5 min in demineralizing solution + 3
      h in remineralizing solution; six cycles a day for 8 days), the samples were
      divided into five groups (n = 5): (E) erosion - control; (ES) erosion + Sensodyne
      Repair & Protect (NovaMin); (EL) erosion + Er:YAG laser (40 mJ, 10 Hz, 0.4 W, 50
      MUs, 3.1 J/cm2, 63 W/cm2); (ELS) erosion + Er:YAG laser + Sensodyne; and (ESL)
      erosion + Sensodyne + Er:YAG laser. Following storage in ultrapure water (37 
      degrees C/14 days), the Ca/P ratio was evaluated by EDXRF and the morphology
      surfaces examined in SEM. The percentage of exposed dentin tubules was
      calculated. One-way analysis of variance and Tukey's test at 5% were used to
      treat the data. The Ca/P ratio was higher in E and ES groups. More exposed dentin
      tubules were found in E group and less exposed tubules were found in the ES group
      (p < 0.0001). When the toothpaste and laser were combined, the number of occluded
      dentin tubules was higher when laser was performed first (ELS). A positive effect
      was found when the laser and toothpaste were combined.

PMID- 29582262
TI  - Distribution of heavy metals and associated human health risk in mine,
      agricultural and roadside soils at the largest chromite mine of India.
AB  - This study accessed the levels of Cd, Cr, Fe, Mn, Ni, Pb and Zn concentration in
      soils of different locations (mine, roadside, agricultural and control sites) of
      Sukinda chromite mine (the India's largest Chromite mine and listed among the
      world's ten most polluted regions). Geo-accumulation (Igeo) index indicates that
      the mine, agricultural and roadside soils are 'heavily to extremely contaminated'
      due to Cr, Ni, Pb and Cd, hence human residing/working in this region can have
      health hazards due to contaminated soil via different exposure pathways. The
      concentration of heavy metals (mg/kg) in mine site vary between 52.35 and 244.8
      (Cr6+), 12,030.2 and 31,818.6 (Cr3+), 5460.4 and 8866.0 (Ni), 70.02 and 208.6
      (Pb), 0.95 and 5.3 (Cd), 209.1 and 360.4 (Mn), 21,531.8 and 28,847 (Fe) and 221
      and 349.3 (Zn). Fe, Cr6+, Cr3+ and Ni concentration in soil follows an order of
      mine site > road sites > agricultural lands > control forest sites. Principal
      component analysis and hierarchical cluster analysis indicate Cd, Cr, Fe, Ni and
      Pb as major pollutants in the region. Cancer Risk is 'high' in both adult (5.38E
      04) and children (4.45E-04) in mining sites and 'low' to 'very low' in
      agricultural and road side soils. The hazard index for all the heavy metals in a
      mining areas is varied from 2.9 to 5.2 in adult and 2.8-5.1 in children,
      indicating 'high' to 'very high' non-cancer risk due to significant contribution
      of Ni, Pb and Cr6+ concentration (73, 11 and 10%, respectively).

PMID- 29582263
TI  - Heavy metal speciation, leaching and toxicity status of a tropical rain-fed river
      Damodar, India.
AB  - Speciations of metals were assessed in a tropical rain-fed river, flowing through
      the highly economically important part of the India. The pattern of distribution
      of heavy metals (Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn) were evaluated in water and
      sediment along with mineralogical characterization, changes with different water
      quality parameters and their respective health hazard to the local population
      along the Damodar River basin during pre-monsoon and post-monsoon seasons. The
      outcome of the speciation analysis using MINTEQ indicated that free metal ions,
      carbonate, chloride and sulfate ions were predominantly in anionic inorganic
      fractions, while in cationic inorganic fractions metal loads were negligible.
      Metals loads were higher in sediment phase than in the aqueous phase. The
      estimated values of Igeo in river sediment during both the seasons showed that
      most of the metals were found in the Igeo class 0-1 which represents unpolluted
      to moderately polluted sediment status. The result of partition coefficient
      indicated the strong retention capability of Cr, Pb, Co and Mn, while Cd, Zn, Cu
      and Ni have resilient mobility capacity. The mineralogical analysis of sediment
      samples indicated that in Damodar River, quartz, kaolinite and calcite minerals
      were dominantly present. The hazard index values of Cd, Co and Cr were > 1 in
      river water, which suggested potential health risk for the children. A
      combination of pragmatic, computational and statistical relationship between
      ionic species and fractions of metals represented a strong persuasion for
      identifying the alikeness among the different sites of the river.

PMID- 29582264
TI  - Association between skin lesion and arsenic concentration in hair by mixed
      bivariate model in chronic arsenic exposure.
AB  - Skin lesion is one of the important health hazards caused by high intake of
      arsenic through drinking water and diet, and the other hazards include several
      types of cancers (viz. skin, lung and urinary bladder), ischemic heart disease,
      hypertension, etc. Two most important biomarkers to measure arsenic intake in a
      human body are arsenic concentration in urine and hair. The primary interest of
      this paper is the association between skin lesion and arsenic concentration in
      hair for participants with chronic arsenic exposure from West Bengal, India,
      using bivariate regression model based on copula function. The result showed
      participants with high arsenic concentration in hair had higher incidence of
      developing skin lesion. Arsenic concentration in hair was significantly higher
      for the participants with an arsenic concentration in water > 10 mg/L.

PMID- 29582265
TI  - Source identification, environmental risk assessment and human health risks
      associated with toxic elements present in a coastal industrial environment,
      India.
AB  - This study investigated the source and contamination levels of toxic elements
      (Cd, Cr, As, Pb, Ni and Hg) present in a coastal environment, Paradip-an
      industrial hub of the east coast of India. The ecological risk assessment indices
      and human exposure models were used to evaluate the pollution status. Enrichment
      factor indicated that all the metal(loid)s found in the sediment are mostly
      derived from the anthropogenic source. According to the sediment quality
      quotient, 8.33% of sediments have crossed the ERM limit for Ni that can be fatal
      to biota. Meanwhile, 66.66, 41.66 and 8.33% of sediments have exceeded PEL range
      for Cr, Ni and As, respectively, that can register frequent lethal toxicity to
      benthic biota. As had the highest potential ecological harm coefficient (Erf >
      80), and Hg had moderate ecological harm coefficient (40 < Erf < 80). Summarily,
      the sediment quality of this site is moderate to heavily toxic to benthic
      organisms. The concentration of toxic metals in seawater was below the
      permissible limit (CCC and CMC) set by USEPA indicating that water is relatively
      safer for free floating aquatic biota. The health risk index of toxic metal
      (loid)s present in soils of the residential sites has confirmed that there is a
      severe non-carcinogenic threat for children (HI child > 1) and a borderline
      carcinogenic risk for both adult and children. THQCr possesses highest non
      carcinogenic threat, which contributed approximately 50% to HI followed by THQAs.
      The contribution of carcinogenic risk of chromium (CRCr) to TCR is approximately
      60%. Cr is the significant contaminant of this site that has highest health
      effects. Highest exposure risks were associated with ingestion pathway accounting
      for about 85% of the total for most of the elements.

PMID- 29582266
TI  - "Voyeuristic Disorder": Etymological and Historical Note.

PMID- 29582267
TI  - Public Perception of Female Fertility: Initial Fertility, Peak Fertility, and Age
      Related Infertility Among U.S. Adults.
AB  - Perceptions of fertility are thought to impact reproductive behaviors, yet little
      is known about how lay people conceptualize the female fertility timeline. In
      this research, public perception of the female fertility timeline was assessed
      via a national survey of U.S. adults (N = 990) ranging in age from 18 to 89
      years. Although there is no scientific consensus on the makeup of the female
      fertility timeline, results from this research indicate that the U.S. public
      posits fertility onset at (approximately) 13 years, peak fertility at 22, ideal
      first pregnancy age at 23, too late for pregnancy at 46, and infertility at 49.
      Regression analysis revealed that perceived peak fertility and ideal pregnancy
      age were positively correlated such that participants perceived the ideal
      pregnancy age as directly following peak fertility. Education was significantly
      related to fertility perceptions; those with more education perceived initial
      fertility to be lower and peak fertility and ideal pregnancy age to be higher. In
      other words, more highly educated individuals perceived fertility to manifest
      over a longer period of time as compared to individuals with less education.
      Black and Hispanic participants and participants with lower income perceived
      ideal first pregnancy age as significantly lower than did White participants and
      participants with higher income. These differences may suggest that the seeds of
      health disparities associated with phenomena such as adolescent pregnancy are
      lurking in fertility timeline perceptions.

PMID- 29582268
TI  - Effects of Sexual Arousal and Alcohol Cues on Acute Motivation for Alcohol.
AB  - Reward-related stimuli can induce motivation to obtain rewards both within and
      across domains. We tested within- and cross-domain effects of environmental
      context (mock bar vs. laboratory) and sexually arousing stimuli (pornography vs.
      nature film) on acute motivation for alcohol as measured by a state-based alcohol
      purchase task in 109 male and female college students. Our results showed
      significant effects of both sexual arousal and environmental context on acute
      motivation for alcohol. A limited subsample analysis (N = 84) revealed
      significant effects of both sexual arousal and environmental context conditions
      on elasticity. Consistent with hypotheses, the presence of either sex- or alcohol
      related cues increased acute motivation for alcohol and decreased sensitivity to
      costs of drinking. Furthermore, there was a significant video * laboratory
      condition interaction in the elasticity analysis. Our findings suggest that both
      sexually arousing stimuli and incidental environmental alcohol cues may
      significantly increase the effort one will expend to consume alcohol and thus the
      potential for risky drinking behavior. We believe this is the first experiment to
      use demand curves to present evidence of cross-domain effects of sexually
      arousing stimuli on acute motivation for alcohol.

PMID- 29582269
TI  - Sexual Probability Discounting: A Mechanism for Sexually Transmitted Infection
      Among Undergraduate Students.
AB  - Lack of condom use among youth is a major contributor to the spread of sexually
      transmitted infections (STIs) including HIV/AIDS, which has lifelong deleterious
      health consequences. College students (N = 262) completed the Sexual Probability
      Discounting Task in which participants reported their likelihood of condom use
      under various probabilities of contracting an STI. Each participant completed the
      task in regard to different STIs including HIV/AIDS and different partners.
      Results showed that the likelihood of condom-protected sex generally decreased as
      HIV/AIDS and other STI contraction became less probable. Moreover, condom
      protected sex likelihood was related to STI type (e.g., decreased condom
      protected sex in chlamydia relative to HIV/AIDS condition) and partner
      desirability (decreased condom-protected sex with more desirable partners).
      Results are the first to show that compared to other STIs, HIV/AIDS had the most
      influence on condom-protected sex. Results showed probability discounting
      contributed to lack of condom-protected sex and offers a novel framework for
      examining determinants of within-subject variability in condom use.

PMID- 29582270
TI  - Indications for salvage surgery during treatment for intracranial germ cell
      tumors.
AB  - This study retrospectively reviewed our single institute experience to clarify
      the optimal indication and timing of salvage surgery. Retrospective analysis of
      159 consecutive cases with germ cell tumors identified 20 cases with salvage
      surgery. These cases were classified based on the radiological response to
      neoadjuvant treatment before salvage surgery into increase (growing group, five
      cases), no change (stable group, seven cases), and decrease (shrinkage group,
      eight cases) in tumor size. Changes in tumor markers, histological findings, and
      the pattern of failure after salvage surgery were reviewed. Growing teratoma
      syndrome (GTS) is defined as enlargement of tumor consisting of mature teratoma
      after chemotherapy with normalization of tumor markers. In growing group, two
      cases presented GTS, whereas other three cases did not fulfill the criteria for
      GTS. All cases in stable and shrinkage group had elevated levels of tumor markers
      at presentation and decreased levels after neoadjuvant treatment. Histologically,
      sparse components of mature teratoma with extensive fibrosis were found in cases
      with GTS and seven of eight cases in shrinkage group, whereas mature teratoma
      without fibrosis was found in six of seven cases in stable group. Six cases
      recurred after salvage surgery. We identified three factors as risks for
      recurrence after salvage surgery, as follows: (1) growing lesion which did not
      fulfill the criteria for GTS, (2) non-normalized level of tumor marker before
      salvage surgery, and (3) residual germinoma component. In conclusion, salvage
      surgery is recommended for patients with GTS, or with normalized tumor markers in
      stable or shrinkage group.

PMID- 29582272
TI  - [Tick-borne encephalitis].

PMID- 29582273
TI  - [Chronic diarrhea - rational diagnostic and therapy].

PMID- 29582271
TI  - Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes
      are differentially expressed within molecular subgroups.
AB  - INTRODUCTION: Medulloblastoma (MB) is an embryonal tumour that originates from
      genetic deregulation of cerebellar developmental pathways and is classified into
      4 molecular subgroups: SHH, WNT, group 3, and group 4. Hydroxymethylation levels
      progressively increases during cerebellum development suggesting a possibility of
      deregulation in MB pathogenesis. The aim of this study was to investigate global
      hydroxymethylation levels and changes in TET and IDH gene expression in MB
      samples compared to control cerebellum samples. METHODS: The methods utilized
      were qRT-PCR for gene expression, dot-blot and immunohistochemistry for global
      hydroxymethylation levels and sequencing for the investigation of IDH mutations.
      RESULTS: Our results show that global hydroxymethylation level was decreased in
      MB, and low 5hmC level was associated with the presence of metastasis. TET1
      expression levels were decreased in the WNT subgroup, while TET3 expression
      levels were decreased in the SHH subgroup. Reduced TET3 expression levels were
      associated with the presence of events such as relapse and death. Higher
      expression of IDH1 was observed in MB group 3 samples, whereas no mutations were
      detected in exon 4 of IDH1 and IDH2. CONCLUSION: These findings suggest that
      reduction of global hydroxymethylation levels, an epigenetic event, may be
      important for MB development and/or maintenance, representing a possible target
      in this tumour and indicating a possible interaction of TET and IDH genes with
      the developmental pathways specifically activated in the MB subgroups. These
      genes could be specific targets and markers for each subgroup.

PMID- 29582274
TI  - [Herpes zoster].

PMID- 29582276
TI  - ?

PMID- 29582275
TI  - [Rotten bones - no way].

PMID- 29582277
TI  - ?

PMID- 29582278
TI  - ?

PMID- 29582280
TI  - ?

PMID- 29582279
TI  - ?

PMID- 29582281
TI  - ?

PMID- 29582282
TI  - ?

PMID- 29582284
TI  - ?

PMID- 29582283
TI  - ?

PMID- 29582285
TI  - [Cannabis in headache treatment].

PMID- 29582286
TI  - ?

PMID- 29582287
TI  - ?

PMID- 29582288
TI  - ?

PMID- 29582289
TI  - ?

PMID- 29582290
TI  - ?

PMID- 29582291
TI  - ?

PMID- 29582292
TI  - ?

PMID- 29582293
TI  - ?

PMID- 29582295
TI  - ?

PMID- 29582296
TI  - ?

PMID- 29582294
TI  - ?

PMID- 29582297
TI  - ?

PMID- 29582298
TI  - ?

PMID- 29582299
TI  - ?

PMID- 29582300
TI  - ?

PMID- 29582301
TI  - ?

PMID- 29582302
TI  - ?

PMID- 29582303
TI  - ?

PMID- 29582305
TI  - ?

PMID- 29582304
TI  - ?

PMID- 29582306
TI  - ?

PMID- 29582307
TI  - ?

PMID- 29582308
TI  - ?

PMID- 29582310
TI  - ?

PMID- 29582312
TI  - ?

PMID- 29582311
TI  - ?

PMID- 29582313
TI  - ?

PMID- 29582314
TI  - [Eating disorders].

PMID- 29582315
TI  - [Pulmonary embolism].

PMID- 29582317
TI  - Outcomes in syncope research: it is time to standardize.

PMID- 29582319
TI  - CME instructions: Myocardial 123I-metaiodobenzylguanidine imaging in hypertension
      and left ventricular hypertrophy.

PMID- 29582318
TI  - Clinical mimics: an emergency medicine focused review of pneumonia mimics.
AB  - Pneumonia is a common cause of morbidity and mortality in adults in the United
      States. While pneumonia classically presents with a fever, cough, and shortness
      of breath, the presentation can vary widely in adults. This review evaluates
      history and physical examination findings of pneumonia and several conditions
      that mimic pneumonia. Pneumonia is a potentially deadly disease. History and
      examination findings are variable in pneumonia, and many conditions mimic
      pneumonia. These conditions include pulmonary embolism, diffuse interstitial lung
      disease, endocarditis, vasculitis, diffuse alveolar hemorrhage, acute
      decompensated heart failure, tuberculosis, lung cancer, and acute respiratory
      distress syndrome. Emergency clinicians should assess the patient while
      resuscitation occurs. Early antibiotics and the diagnosis of pneumonia can
      improve outcomes. Key historical and physical examination findings may lead the
      clinician to consider other conditions that require immediate management. Using
      clinical evaluation and adjunctive imaging, these conditions can be diagnosed and
      treated. Knowledge of pneumonia mimics is vital for the care of patients with
      respiratory complaints. Pneumonia is common and may be deadly, and emergency
      clinicians must differentiate conditions that mimic pneumonia. Rapid evaluation
      and management may alleviate morbidity and mortality for each of these
      conditions. The history and physical examination, in addition to utilizing
      imaging modalities such as ultrasound and computed tomography, are vital in
      diagnosis of pneumonia mimics.

PMID- 29582320
TI  - Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?
AB  - BACKGROUND: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes
      involved in several cellular processes, including DNA single-strand break repair
      via the base-excision repair pathway. PARP inhibitors exert antitumor activity by
      both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition
      represents a potential synthetic lethal approach against cancers with specific
      DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of
      mesenchymal tumors with locally destructive growth, high risk of recurrence and
      distant metastasis. OBJECTIVES: The purpuse of this review is to provide an
      overview of the main preclinical and clinical data on use of PARPi in STSs and of
      effect and safety of combination of PARPi with irradiation. RESULTS: Due to
      numerous genomic alterations in STSs, the DNA damage response pathway can offer
      an interesting target for biologic therapy. Preclinical and clinical studies
      showed promising results, with the most robust evidences of PARPi efficacy
      obtained on Ewing sarcoma bearing EWS-FLI1 or EWS-ERG genomic fusions. The
      activity of PARP inhibitors resulted potentiated by chemotherapy and radiation.
      Although mechanisms of synergisms are not completely known, combination of
      radiation therapy and PARP inhibitors exerts antitumor effect by accumulation of
      unrepaired DNA damage, arrest in G2/M, activity both on oxic and hypoxic cells,
      reoxygenation by effect on vessels and promotion of senescence. Early trials have
      shown a good tolerance profile. CONCLUSIONS: The use of PARP inhibitors in
      advanced stage STSs, alone or combined in multimodal treatments, is of great
      interest and warrants further investigations.

PMID- 29582321
TI  - Diagnostic performance of shoulder magnetic resonance arthrography for labral
      tears having surgery as reference: comparison of high-resolution isotropic 3D
      sequence (THRIVE) with standard protocol.
AB  - PURPOSE: To compare the diagnostic performance of T1 high-resolution isotropic
      volume excitation (THRIVE) sequence with that of a standard protocol for direct
      shoulder magnetic resonance arthrography (MRA) for the diagnosis of superior
      labral anterior-to-posterior (SLAP) and Bankart lesions, using arthroscopy
      findings as a reference standard. MATERIALS AND METHODS: We retrospectively
      studied 84 patients who underwent direct shoulder 3T MRA using THRIVE and two
      dimensional three-plane proton-density fat-suppressed (2D-PD-FS) sequences. One
      reviewer evaluated the contrast-to-noise ratio (CNR) as a quantitative image
      quality. Other two reviewers independently evaluated the subjective image noise,
      image sharpness, and radiologic diagnosis as qualitative image quality.
      Arthroscopic surgical findings were considered the reference standard. Wilcoxon
      rank sum, Chi-square/Fisher's exact, and DeLong's tests, as well as intraclass
      correlation coefficients (ICCs) were used to evaluate differences between THRIVE
      and 2D-PD-FS images. RESULTS: THRIVE images had significantly higher CNR (p <
      0.001), and subjective ratings of image noise (p = 0.009) and sharpness (p =
      0.039) than 2D-PD-FS images (p < 0.001). THRIVE images had similar (p >= 0.18)
      diagnostic performance (sensitivity, 93.0-97.2%; specificity, 95.8-100%;
      accuracy, 95.2-97.6%) for the diagnosis of SLAP and Bankart lesions with
      excellent agreement (ICC = 0.898-0.942) when compared to 2D-PD-FS images
      (sensitivity, 86.1-91.7%; specificity, 93.8-95.8%; accuracy, 90.5-92.9%;
      agreement, ICC = 0.782-0.858). The scan time was reduced by 69% for THRIVE
      sequence compared to 2D-PD-FS sequence (2 min 40 s vs. 8 min 40 s). CONCLUSION:
      The THRIVE sequence may be helpful in the diagnosis of SLAP and Bankart lesions,
      and may be routinely used during direct shoulder 3T MRA.

PMID- 29582322
TI  - Remediation of cadmium contaminated water and soil using vinegar residue biochar.
AB  - This study investigated a new biochar produced from vinegar residue that could be
      used to remediate cadmium (Cd)-contaminated water and soil. Aqueous solution
      adsorption and soil incubation experiments were performed to investigate whether
      a biochar prepared at 700  degrees C from vinegar residue could efficiently
      adsorb and/or stabilize Cd in water and soil. In the aqueous solution adsorption
      experiment, the Cd adsorption process was best fitted by the pseudo-second-order
      kinetic and Freundlich isotherm models. If the optimum parameters were used,
      i.e., pH 5 or higher, a biochar dosage of 12 g L-1, a 10 mg L-1 Cd initial
      concentration, and 15-min equilibrium time, at 25  degrees C, then Cd removal
      could reach about 100%. The soil incubation experiment evaluated the biochar
      effects at four different application rates (1, 2, 5, and 10% w/w) and three Cd
      contamination rates (0.5, 1, and 2.5 mg kg-1) on soil properties and Cd
      fractionation. Soil pH and organic matter increased after adding biochar,
      especially at the 10% application rate. At Cd pollution levels of 1.0 or 2.5 mg
      kg-1, a 10% biochar application rate was most effective. At 0.5 mg Cd kg-1 soil,
      a 5% biochar application rate was most efficient at transforming the acid
      extractable and easily reducible Cd fractions to oxidizable and residual Cd. The
      results from this study demonstrated that biochar made from vinegar residue could
      be a new and promising alternative biomass-derived material for Cd remediation in
      water and soil.

PMID- 29582323
TI  - Assessment of biotoxicity of Cu nanoparticles with respect to probiotic strains
      of microorganisms and representatives of the normal flora of the intestine of
      broiler chickens.
AB  - Copper nanoparticle Cu (d = 55 +/- 15 nm) and CuO nanoparticles (d = 90 +/- 10
      nm) were used in the studies (OOO Platina, Russia). Using the method of pure
      cultures, we extracted Lactobacillus, Enterococcus, and Enterobacterium from the
      intestines of broilers. Additionally, strains of Bacillus subtilis 10641 and
      Bifidobacterium were involved in probiotic strains. The data obtained in the
      course of the study testify to the insignificant biotoxicity of copper
      nanoparticles with respect to representatives of the genera Lactobacillus (30 to
      15 MUg/ml) and Bifidobacterium (30 MUg/ml), with the most sensitive bacteria
      being the genus Lactobacillus, for which a concentration of 7.5 MUg/ml was
      subinhibitory. The second stage was the study using method of agar wells. In the
      course of the experiment, we obtained results confirming the data of the research
      by the serial dilution method. In this case, as in the first case, the data
      indicate the insignificant biotoxicity of copper nanoparticles in relation to
      representatives of the genera Lactobacillus and Bifidobacterium. We have studied
      the bioaccumulating ability of microorganisms of the studied metals. In all the
      studies carried out, as in the first series of experiments, representatives of
      the genera Lactobacillus and Bifidobacterium with the lowest bioaccumulative
      ability were the most sensitive to copper nanoparticles and were 3.1 and 8.2%,
      respectively. The use of nanoparticles as a component of the fodder additive in
      small concentrations does not adversely affect not only the probiotic strains,
      but also the main representatives of the normoflora (Lactobacillus, Enterococcus,
      and Enterobacterium) of the poultry, the positive effect of the copper
      nanoparticles being directly related to low level of dissociation of
      nanoparticles, since biologically active ions will be released much more slowly,
      thereby creating a prolonged effect of exposure.

PMID- 29582324
TI  - Caffeine levels as a predictor of Human mastadenovirus presence in surface waters
      a case study in the Sinos River basin-Brazil.
AB  - The presence of caffeine in environmental water samples is almost entirely human
      related, given that there are virtually no industrial or agricultural releases.
      Caffeine has already been proposed as an anthropogenic marker for wastewater
      contamination of surface waters. The aim of this study was to evaluate if
      caffeine concentrations in water can be a predictor of virological and
      bacteriological contamination. Water samples were taken at three sampling sites
      from urban water streams from the hydrographic basin of the Sinos River (Brazil)
      monthly in the period of May 9th, 2016 to April 11th, 2017 (n = 36).
      Concentrations of Human mastadenovirus (HAdV-F and HAdV-C), fecal coliforms, and
      caffeine were measured in all collected samples. Concentrations of caffeine in
      water were strongly correlated with HAdV-F (rs = 0.704, p = 0.000). This study,
      for the first time, characterized caffeine concentrations in water as predictors
      of virus presence, with cut-off values presenting 92.9% specificity and 95.5%
      sensitivity for HAdV-F and 66.7% specificity and 80% sensitivity for HAdV-C.
      Considering its marked chemical stability and ease of quantification, caffeine
      concentrations can be used as a comprehensive marker of human contamination of
      water resources, also being predictive of bacteriological and virological
      concentrations.

PMID- 29582325
TI  - Protective effect of grape or apple juices in bone tissue of rats exposed to
      cadmium: role of RUNX-2 and RANK/L expression.
AB  - The aim of this study was to investigate if grape or apple juices are able to
      protect bone tissue of rats exposed to cadmium. For this purpose,
      histopathological analysis and immunohistochemistry for RUNX-2 and RANK-L were
      investigated in this setting. A total of 20 adult Wistar rats were distributed
      into four groups (n = 5), as follows: control group, cadmium group, cadmium and
      grape juice group, and Cadmium and apple juice group. Control group received a
      single intraperitoneal (i.p.) water injection. Cadmium group received a single
      i.p. injection of cadmium chloride (1.2 mg/kg body weight) diluted in water.
      Cadmium and grape juice and cadmium and apple juice groups received a single i.p.
      injection of cadmium chloride (1.2 mg/kg body), and after 15 days, the rats were
      treated with grape or apple juices for 15 days, by gavage. All animals were
      euthanized 30 days after the beginning of experiment. Histopathological analysis
      in rat femur revealed extensive bone loss in rats intoxicated with cadmium. Grape
      or apple juices were able to increase bone formation. Cadmium inhibited RUNX-2
      immunoexpression whereas cadmium increased RANK-L immunoexpression in rat bone
      cells. Grape or apple juices increased RUNX-2 and decreased RANK-L
      immunoexpression after cadmium intoxication. Taken together, our results
      demonstrate that grape or apple juices are able to exert therapeutic activity
      following cadmium intoxication in rat bone tissue as result of stimulatory effect
      of bone formation by RUNX-2 upregulation and RANK-L downregulation.

PMID- 29582326
TI  - Using carbonized low-cost materials for removal of chemicals of environmental
      concern from water.
AB  - Adsorption on low-cost biochars would increase the affordability and availability
      of water treatment in, for example, developing countries. The aim of this study
      was to identify the precursor materials and hydrochar surface properties that
      yield efficient removal of compounds of environmental concern (CEC). We
      determined the adsorption kinetics of a mixture containing ten CECs (octhilinone,
      triclosan, trimethoprim, sulfamethoxasole, ciprofloxacin, diclofenac,
      paracetamol, diphenhydramine, fluconazole, and bisphenol A) to hydrochars
      prepared from agricultural waste (including tomato- and olive-press wastes, rice
      husks, and horse manure). The surface characteristics of the hydrochars were
      evaluated via diffuse reflectance infrared spectroscopy (DRIFTS), X-ray
      photoelectron spectroscopy (XPS), and N2-adsorption. Kinetic adsorption tests
      revealed that removal efficiencies varied substantially among different
      materials. Similarly, surface analysis revealed differences among the studied
      hydrochars and the degree of changes that the materials undergo during
      carbonization. According to the DRIFTS data, compared with the least efficient
      adsorbent materials, the most efficient hydrochars underwent more substantial
      changes during carbonization.

PMID- 29582316
TI  - Major adverse cardiovascular events in non-valvular atrial fibrillation with
      chronic obstructive pulmonary disease: the ARAPACIS study.
AB  - Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in
      non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of
      COPD to major cardiovascular events (MACE) in AF have not been defined. The aim
      of the study is to assess the predictive value of COPD on incident MACE in NVAF
      patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle
      Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)
      cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE
      (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular
      (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD
      (9%) are more commonly male, elderly and at higher thromboembolic risk. During a
      median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n =
      72), MI (n = 57), stroke/TIA (n = 57). All major outcomes (including stroke/TIA,
      MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan-Meier
      curves show that NVAF patients with COPD are at higher risk for MACE (p < 0.001),
      CV death (p < 0.001) and all-cause death (p < 0.001). On Cox proportional hazard
      analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95%
      Confidence Intervals [CI] 1.20-2.61; p = 0.004), CV death (HR 2.73, 95% CI 1.76
      4.23; p < 0.0001) and all-cause death (HR 2.16, 95% CI 1.48-3.16; p < 0.0001).
      COPD is an independent predictor of MACE, CV death and all-cause death during a
      long-term follow-up of NVAF patients.

PMID- 29582327
TI  - Assessment of the effects of different tree species on urban microclimate.
AB  - Trees in urban areas are important for their ecological functions in addition to
      their esthetic characteristics. Trees provide positive effects on urban
      microclimate by canopy, reflection, and transpiration activities; therefore, they
      help to decline formation of heat island. The objective of this study was to
      determine thermal effects of 15 different tree types: 4 coniferous and 11
      deciduous species commonly found in the city of Erzurum located at the
      northeastern part of Turkey. The relationships between sky view factor and
      surface temperature regarding the differences in leaf density and tree species.
      In August 2016, the surface temperature of trees was measured using a thermal
      camera at 10:00 am and 4:00 pm hours. Sky view factor (SVF) was obtained by
      fisheye photos and physiologically characteristics of trees were determined. In
      all trees while the surface temperature was 20.1  degrees C at 10:00 am, it was
      23.4  degrees C at 4:00 pm. Among the deciduous tree species, Betula verrucosa
      Ehrh. and Robinia pseudoacacia "Umbracuifera" had the lowest surface temperature;
      however, Abies concolor (Gord. & Glen.) had the lowest surface temperature among
      the coniferous tree species. The results indicated that the surface temperatures
      of different tree species varied considerably, and the SVF value had a
      significant effect on tree surface temperatures. However, it was obtained that
      the leaf types had no statistically significant effect on tree surface
      temperature.

PMID- 29582328
TI  - Effects of exogenous sulfur on growth and Cd uptake in Chinese cabbage (Brassica
      campestris spp. pekinensis) in Cd-contaminated soil.
AB  - Soil pollution with heavy metals has many adverse effects on ecosystem health as
      well as food security. A pot experiment was performed to investigate the effects
      of different valence states of exogenous sulfur (S) on the uptake of cadmium (Cd)
      in Chinese cabbage in Cd-contaminated soil. The results showed that S
      significantly promoted plant growth in Chinese cabbage, with the following order
      of magnitude for the different S treatments: sodium sulfite (Na2SO3) > sodium
      sulfate (Na2SO4) > powdered sulfur (S0). Additionally, enzyme activity and the
      content of reductive substances in the leaves markedly increased, while
      malondialdehyde content significantly decreased; hence, S observably enhanced the
      ability of Chinese cabbage to tolerate Cd stress. S0 significantly reduced soil
      pH, thus increasing the mobility and bioavailability of Cd in the soil, while
      Na2SO3 increased soil pH, and Na2SO4 had no effect on soil pH. The acid-soluble
      and oxidizable fractions of Cd in soil increased with the S0 treatment. The
      applied Na2SO3 and Na2SO4 both increased the residual fraction of Cd in the soil,
      but they reduced the amount of the acid-extractable, reducible, and oxidizable
      Cd. The results showed that compared with S0, the Na2SO3 and Na2SO4 treatments
      decreased the acid-extractable Cd concentrations by 6.3 and 4%, respectively, in
      the most contaminated soil. In conclusion, the influence of S on the
      bioavailability and speciation of Cd varied not only with the soil Cd content but
      also with the application rate and S valence state.

PMID- 29582329
TI  - Distribution and hydrogeochemical behavior of arsenic enriched groundwater in the
      sedimentary aquifer comparison between Datong Basin (China) and Kushtia District
      (Bangladesh).
AB  - A prompt growth in research on arsenic occurrence and behavior in the environment
      has occurred over the last decade or so. High arsenic (As) in groundwater has
      become a major global concern due to its widespread occurrence. A comparative
      hydrogeochemical study was performed on the occurrence of high As groundwater in
      Datong Basin, China, and Kushtia District, Bangladesh. A total of 132 groundwater
      samples (83 from Datong Basin and 49 from Kushtia District) were collected to
      analyze the major hydrogeochemical components and trace elements in groundwater
      of both areas. Factor analysis (FA) was applied on the hydrochemical data to
      identify the major hydrogeochemical processes in sedimentary aquifers. High As
      groundwater was observed in the low-lying central parts of Datong Basin, which
      are composed of the Holocene alluvial and lacustrine aquifers. The elevated As
      concentrations ranged from 0.31 to 452 MUg/L and distributed in depths between 20
      and 45 m. As-enriched groundwater is mainly Na-HCO3 type water and characterized
      by higher pH value, high Na+, low Ca2+, SO42-, and NO3- along with moderate TDS.
      The alkaline and reducing subsurface environment facilitate the leaching of As in
      sedimentary aquifers. The release and distribution of As in aquifers are resulted
      from the reduction of As-carrying crystalline iron (Fe) oxide/hydroxides and
      oxidation of organic matter. The aquifers of Kushtia District, Bangladesh, are
      unconsolidated, alluvial in nature, and developed from Holocene floodplain and
      Pleistocene deposits. High As (6.04-590.7 MUg/L) groundwater occurs mainly in
      shallow aquifers. The Ca-HCO3 type groundwater is distinguished by circum-neutral
      pH, medium-high EC, high HCO3-, and low content of NO3-, SO42-, K+, and Cl-. The
      reductive suspension of MnOOH increases the dissolved As loads and redox
      responsive elements such as SO42- and pyrite oxidation act as the main mechanisms
      for As release in groundwater. As is mobilized by anaerobic leakage from the
      brown-clay and gray-sand into the sediment. Infiltration from irrigation return
      and surface wash water are the potential factors that remobilize As. The weak
      loading of Fe suggests that the release of Fe and As is decoupled in sedimentary
      aquifers of Kushtia District.

PMID- 29582330
TI  - Screening of groundwater remedial alternatives for brownfield sites: a
      comprehensive method integrated MCDA with numerical simulation.
AB  - Brownfield sites pollution and remediation is an urgent environmental issue
      worldwide. The screening and assessment of remedial alternatives is especially
      complex owing to its multiple criteria that involves technique, economy, and
      policy. To help the decision-makers selecting the remedial alternatives
      efficiently, the criteria framework conducted by the U.S. EPA is improved and a
      comprehensive method that integrates multiple criteria decision analysis (MCDA)
      with numerical simulation is conducted in this paper. The criteria framework is
      modified and classified into three categories: qualitative, semi-quantitative,
      and quantitative criteria, MCDA method, AHP-PROMETHEE (analytical hierarchy
      process-preference ranking organization method for enrichment evaluation) is used
      to determine the priority ranking of the remedial alternatives and the solute
      transport simulation is conducted to assess the remedial efficiency. A case study
      was present to demonstrate the screening method in a brownfield site in Cangzhou,
      northern China. The results show that the systematic method provides a reliable
      way to quantify the priority of the remedial alternatives.

PMID- 29582331
TI  - Occurrence and toxicological assessment of polycyclic aromatic hydrocarbons
      (PAHs) in marine sediments under mussel farming influence.
AB  - The use of marine resources for mussel culture has become increasingly important,
      particularly on the European Atlantic coast and notably in the Galician Rias in
      the northwest of Spain. Despite its importance, there is a lack of research and
      analysis in this area and of the potential problems that it could cause to the
      environment. This paper details the findings of a study that aimed to find the
      probable environmental impact of mussel culture activities and to evaluate the
      polycyclic aromatic hydrocarbon (PAH) content derived from this activity. The Ria
      de Arousa, where you can find over 70% of all installed rafts in Galicia, was
      selected for the present study, and nearly 40 marine sediment samples were
      collected there. The sediments were extracted by ASE (accelerated solvent
      extraction) procedure, and the quantification of PAHs was performed using gas
      chromatography coupled to mass spectrometry (GC-MS), with the aid of deuterated
      PAH internal standards. The total concentration of parental PAHs ranged from
      11.66 to 30,272-ng g-1 dry weight (d.w.), with a mean value of 3907-ng g-1 d.w.;
      the concentration of alkyl PAHs varied from 3.72 to 1187-ng g-1 d.w., with a mean
      value of 205.1-ng g-1 d.w. Compositional patterns, principal component analysis
      (PCA) and hieratical cluster association (HCA) yielded a sediment classification
      where the mussel raft impact is pointed out. PAH ratios indicated a predominance
      of combustion sources, except in two samples, located in small harbors. Only one
      station showed total potential carcinogenic PAH values in the range that would
      frequently cause negative biological effects, and the toxic equivalent
      concentrations based on BaP equivalents identified another ten positions where
      biological effects would occur occasionally.

PMID- 29582332
TI  - The copper complexation ability of a synthetic humic-like acid formed by an
      abiotic humification process and the effect of experimental factors on its copper
      complexation ability.
AB  - Humic acids have an important impact on the distribution, toxicity, and
      bioavailability of hazardous metals in the environment. In this study, a
      synthetic humic-like acid (SHLA) was prepared by an abiotic humification process
      using catechol and glycine as humic precursors and a MnO2 catalyst. The effect of
      physico-chemical conditions (ionic strength from 0.01 to 0.5 M NaNO3, pH from 4
      to 8, temperature from 25 to 45  degrees C, and humic acid concentration from 5
      to 100 mg/L) on the complexation ability of SHLA for Cu2+ were investigated. A
      commercial humic acid (CHA, CAS: 1415-93-6) from Sigma-Aldrich was also studied
      for comparison. The results showed that for pH 4 to 8, the conditional stability
      constants (log K) of SHLA and CHA were in the range 5.63-8.62 and 4.87-6.23,
      respectively, and complexation capacities (CC) were 1.34-2.61 and 1.42-2.31
      mmol/g, respectively. The Cu complexation ability of SHLA was higher than that of
      the CHA due to its higher number of acidic functional groups (SHLA 19.19 mmol/g;
      CHA 3.87 mmol/g), extent of humification and aromaticity (AL/AR: 0.333 (SHLA);
      1.554 (CHA)), and O-alkyl functional groups (SHLA 15.56%; CHA 3.45%). The log K
      and complexation efficiency (fraction of metal bound to SHLA) of SHLA were higher
      at higher pH, lower ionic strength, higher temperature, and higher SHLA
      concentration. Overall, SHLA was a good and promising complexation agent for
      copper in both soil washing of copper contaminated soil and the treatment of
      copper-containing wastewater.

PMID- 29582333
TI  - Influence of post-transplant mucosal-associated invariant T cell recovery on the
      development of acute graft-versus-host disease in allogeneic bone marrow
      transplantation.
AB  - Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells
      are T cell subpopulations that possess innate-like properties. We examined the
      impact of post-hematopoietic stem cell transplantation (HSCT) MAIT and iNKT cell
      recovery on the clinical outcomes of 69 patients who underwent allogeneic HSCT at
      Kyoto University Hospital. Multivariate analyses identified the absolute number
      of MAIT cells (< 0.48/MUL on day 60 post-HSCT) as the sole independent risk
      factor for grade I-IV and grade II-IV acute graft-versus-host disease (aGVHD)
      among patients who underwent bone marrow transplantation; no correlation was
      observed between post-HSCT iNKT cell recovery and the development of aGVHD. Six
      of the 15 patients in the MAIThigh (>= 0.48/MUL) group developed aGVHD, five
      within the first 30 days post HSCT. In contrast, 13 of the 15 patients in the
      MAITlow (< 0.48/MUL) group developed aGVHD, seven after day 30 post HSCT. The
      overall survival of the MAITlow group was slightly shorter than that of the
      MAIThigh group. Thus, the post-HSCT recovery of MAIT cells is closely related to
      the development of delayed onset aGVHD and the outcome of post-HSCT, suggesting
      its utility for identifying a subset of patients that requires more prolonged
      and/or intense GVHD prophylaxis.

PMID- 29582334
TI  - Acquired hemophilia A associated with autoimmune pancreatitis with serum IgG4
      elevation.
AB  - A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune
      pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in
      2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was
      tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She
      suddenly presented with subcutaneous bleeding in 2015. Her activated partial
      thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor
      pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was
      290 BU/mL. She was diagnosed with AHA. Her serum IgG4 was elevated to 133 mg/dL.
      She was treated first with PSL alone, but she developed bladder tamponade.
      Cyclophosphamide and activated prothrombin complex concentrate were combined with
      PSL. She then achieved hemostasis, and FVIII inhibitor disappeared. FVIII
      inhibitor had been detected since PSL was tapered and AHA recurred two months
      later. An enzyme-linked immunosorbent assay showed that the inhibitor was mainly
      IgG4 and IgG1. This case suggests that elevation of IgG4 may be associated with
      the development of both AHA and AIP.

PMID- 29582335
TI  - Influence of Religious and Spiritual Elements on Adherence to Pharmacological
      Treatment.
AB  - The objective of this study is to know the influence of religious/spiritual
      elements on the adherence to pharmacological therapy. The descriptors used for
      this literature review were "medicine, medication, drug, or treatment,"
      "adherence to treatment," and "religion or spirituality or faith or prayer" in
      different databases (CINAHL, PsycINFO, PubMed). Finally, 23 articles were
      selected. Articles available in full text, published between 2010 and 2017, in
      English or Spanish were included. The results showed that some studies relate
      positively the R/S and therapeutic adherence, but others determine an opposite or
      even mixed effect, mainly addressing pathologies such as HIV and other chronic
      diseases. The influence of religiosity/spirituality on therapeutic adherence
      requires that health professionals acquire sensitivity and competence to address
      these issues with their patients.

PMID- 29582337
TI  - Longitudinal score prediction for Alzheimer's disease based on ensemble
      correntropy and spatial-temporal constraint.
AB  - Neuroimaging data has been widely used to predict clinical scores for automatic
      diagnosis of Alzheimer's disease (AD). For accurate clinical score prediction,
      one of the major challenges is high feature dimension of the imaging data. To
      address this issue, this paper presents an effective framework using a novel
      feature selection model via sparse learning. In contrast to previous approaches
      focusing on a single time point, this framework uses information at multiple time
      points. Specifically, a regularized correntropy with the spatial-temporal
      constraint is used to reduce the adverse effect of noise and outliers, and
      promote consistent and robust selection of features by exploring data
      characteristics. Furthermore, ensemble learning of support vector regression
      (SVR) is exploited to accurately predict AD scores based on the selected
      features. The proposed approach is extensively evaluated on the Alzheimer's
      disease neuroimaging initiative (ADNI) dataset. Our experiments demonstrate that
      the proposed approach not only achieves promising regression accuracy, but also
      successfully recognizes disease-related biomarkers.

PMID- 29582338
TI  - Health-related quality of life in end-stage renal disease patients: the effects
      of starting dialysis in the first year after the transition period.
AB  - BACKGROUND/AIMS: Prevalent dialysis patients have low scores of health-related
      quality of life (HRQOL) which are associated with increased risk of
      hospitalization and mortality. Also in CKD-5 non-dialysis patients, HRQOL scores
      seem to be lower as compared with the general population. This study firstly
      aimed to compare HRQOL between CKD-5 non-dialysis and prevalent dialysis patients
      in a cross-sectional analysis and to assess longitudinal changes over 1 year
      after the dialysis initiation. Secondly, the correlation between HRQOL and
      physical activity (PA) was explored. METHODS: Cross-sectional 44 CKD-5 non
      dialysis, 29 prevalent dialysis, and 20 healthy controls were included. HRQOL was
      measured by Short Form-36 questionnaires to measure physical and mental domains
      of health expressed by the physical component summary (PCS) and mental component
      summary (MCS) scores. PA was measured by a SenseWearTM pro3. Longitudinally,
      HRQOL was assessed in 38 CKD-5 non-dialysis patients (who were also part of the
      cross-sectional analysis), before dialysis initiation until 1 year after dialysis
      initiation. RESULTS: PCS scores were significantly lower both in CKD-5 non
      dialysis patients and in prevalent dialysis patients as compared with healthy
      controls (p < 0.001). MCS scores were significantly lower in both CKD-5 non
      dialysis patients (p = 0.003), and in dialysis patients (p = 0.022), as compared
      with healthy controls. HRQOL scores did not change significantly from the CKD-5
      non-dialysis phase into the first year after dialysis initiation. PA was
      significantly related to PCS in both CKD-5 non-dialysis patients (r = 0.580; p <
      0.001), and dialysis patients (r = 0.476; p = 0.009). CONCLUSIONS: HRQOL is
      already low in the CKD-5 non-dialysis phase. In the first year after dialysis
      initiation, HRQOL did not change significantly. Given the correlation between PCS
      score and PA, physical activity programs may be potential tools to improve HRQOL
      in both CKD-5 non-dialysis as well as in prevalent dialysis patients.

PMID- 29582339
TI  - Prevalence of pulmonary hypertension in patients with chronic kidney disease
      without dialysis: a meta-analysis.
AB  - PURPOSE: Recent epidemiological evidence attempts to demonstrate the risk of
      pulmonary hypertension (PH) among patients with chronic kidney disease (CKD)
      without dialysis, but prevalence estimates of PH in CKD without dialysis vary
      widely in the existing studies. This meta-analysis was to summarize the point
      prevalence of PH in adults with CKD without dialysis. METHODS: PubMed, EMBASE,
      the Cochrane Collaboration, and the reference lists of relevant articles were
      searched to identify eligible studies. We used a random-effect meta-analysis
      model to estimate the prevalence of PH. Associations were tested in subgroups and
      meta-regression analyses. We also performed sensitivity analyses and assessments
      of publishing bias. RESULTS: Twenty-one observational studies (n = 8012
      participants) were included in this meta-analysis. The result of analysis in
      random-effect model showed that the pooled prevalence was 32% (95% CI 23-42%),
      with significant heterogeneity between these studies (I2 = 98%, P < 0.01).
      Stratified analyses found that the study design, region, sample size, year of
      publication, and definition of PH based on PASP >= 35 mmHg may explain the
      variation between studies. Sensitivity analysis further demonstrated the results
      to be robust. There was no evidence of publication bias. CONCLUSIONS: PH is
      highly prevalent in patients with CKD without dialysis. Owing to the high
      heterogeneity, future well-designed and large prospective studies are encouraged
      to confirm the findings and definitively clarify the potential biological
      mechanisms.

PMID- 29582340
TI  - Prevalence of bovine and avian tuberculosis in camel herds and associated public
      health risk factors in Isiolo County, Kenya.
AB  - A cross-sectional study was conducted among 308 lactating camels selected from 15
      herds from three different camel milk clusters in Isiolo County, Kenya, to
      determine prevalence of bovine and avian tuberculosis using Single Comparative
      Intradermal Tuberculin Skin test. Seventy-five (75) questionnaires were
      administered to pastoralists/herders, and focus group discussions were conducted
      among 3-5 pastoralists/herders selected from each camel herd to collect
      information on camel husbandry and health management practices and knowledge on
      tuberculosis in livestock and wildlife. An overall prevalence of bovine and avian
      reactors was 3.57 and 18.18%, respectively, with bovine and avian reactors for
      different clusters being 2.38, 3.82, and 4.48% and 25, 17.2, and 11.94%,
      respectively. There was significant difference (p < 0.05) in prevalence of bovine
      and avian reactors between different clusters. There was a negative correction (r
      = -0.1399) between herd size and bovine reactors, while there was a positive
      correlation (r = 0.0445) between herd size and avian reactors. The respondents
      indicated that camel herds are exposed to several risk factors like close contact
      with other herds or livestock or wildlife during grazing and at watering points.
      Pastoralists have poor knowledge on mode of infection and transmission of bovine
      or avian tuberculosis. The high prevalence of bovine and avian reactors and
      pastoralists' poor knowledge on mode of transmission signify potential risk to
      public health.

PMID- 29582341
TI  - Effect of dietary inclusion of date seed (Phoenix dactylifera L.) on intake,
      digestibility, milk production, and milk fatty acid profile of Holstein dairy
      cows.
AB  - The objective of this experiment was to investigate the influence of ground date
      seed (GDS) on intake, digestibility, and milk yield and milk fatty acid (FA)
      composition of lactating Holstein cows. The experimental design was a 4 * 4
      replicated Latin square with eight lactating dairy cows with an average milk
      production of 35.5 +/- 1.5 kg and 75 +/- 5 days in milk (DIM). Dairy cows were
      fed one of the four treatments contained 0, 2, 4, and 6% of diet dry matter (DM)
      GDS in replacement of wheat bran. All diets contained the same amount of forages
      (alfalfa hay and corn silage). Dietary treatments had no effect on DM intake
      (DMI), total tract apparent digestibility, milk yield, and milk composition.
      Increasing GDS linearly decreased concentration of C13:0 and increased cis-9
      C14:1 and trans-11 C18:1 (vaccenic acid) (P < 0.05). A linear tendency for more
      C16:1 content in milk fat was observed with increasing GDS (P = 0.06). Feeding
      GDS resulted in a linear decrease (P < 0.01) in saturated FA (SFA) but increased
      milk fat monounsaturated FA (MUFA) and trans FA (TFA) (P < 0.05). Therefore, low
      levels of GDS (up to 6%) in the diet of Holstein dairy cows can beneficially
      modify milk FA composition without any adverse effects on intake, digestibility,
      and milk yield.

PMID- 29582343
TI  - Gabriella Morreale de Escobar (1930-2017).

PMID- 29582342
TI  - Performance Evaluation of Community Health Workers: Case Study in the Amazon of
      Peru.
AB  - A shortage in human resources for health is a growing crisis that has led to an
      inability to provide adequate health services to impoverished populations. By
      "task-shifting", health systems can delegate certain activities, such as health
      promotion and referral, to trained community members to help fill the human
      resource gap. An effective community health agent program can improve maternal
      and child health and overall effectiveness of rural health systems. Such a
      program is most effective when the community health agents receive supervision
      and evaluation of their performance. There is a shortage of literature that
      provides instruction and example on how to conduct a performance evaluation in
      the developing world to improve maternal and child health outcomes. The current
      study provides a case study of a performance evaluation in the Amazon region of
      Peru and how the findings can be used to make program adjustments. A set of
      instruments to measure the performance of CHWs was adapted from the literature
      and then implemented in the field. The instruments were used to measure the
      quality of home visits by the CHWs, their knowledge of the health topics, and
      structural activities. Three communities with an active CHW program in Loreto,
      Peru were chosen to receive the evaluation. All CHWs in the communities were
      evaluated. The scores from the evaluation were compared internally to identify
      strengths and weaknesses of the program and within the population of CHWs. The
      evaluation was completed on 52 home visits and 27 CHWs in three communities. The
      CHWs were found to be most effective at creating good relationships with
      caregivers and delivering health messages, and least effective at interacting
      with the child during the home visit and using material to deliver health
      messages. The evaluation instruments were well suited for the CHW program that
      utilizes home visits to teach about child health and development.

PMID- 29582344
TI  - TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast
      or 30 min before breakfast.
AB  - PURPOSE: To compare TSH levels of hypothyroid patients treated with liquid LT4 at
      breakfast or 30 min before breakfast. PATIENTS AND METHODS: Subjects, aged 18-75
      years old, were eligible if they presented hypothyroidism, due to Hashimoto's
      thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety
      eight patients were recruited and enrolled in the study. Thirty-seven subjects
      withdrew from the trial. A total of 761 patients (mean age 46.2 +/- 10.8 years)
      completed the study. The starting dose of LT4 was determined through clinical
      judgment, taking into account TSH levels, estimated residual thyroid function,
      age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3
      evaluation to verify achievement of euthyroidism with their initial fasting state
      assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an
      appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid
      function parameters were checked again. If euthyroidism was achieved, the
      patients were asked to take LT4 at breakfast and hormone levels were checked
      again after 6 months. RESULTS: At the end of the study period, no significant
      differences in serum TSH level were observed whether LT4 was ingested at
      breakfast or 30 min prior in a fasting state: 2.61 +/- 1.79 vs. 2.54 +/- 1.86
      mIU/L, respectively (p = 0.455). CONCLUSIONS: This study confirms in a large set
      of patients that a liquid LT4 formulation can be taken directly at breakfast and
      potentially improve therapeutic compliance.

PMID- 29582345
TI  - Absence of cellular damage in tropical newly hatched sharks (Chiloscyllium
      plagiosum) under ocean acidification conditions.
AB  - Sharks have maintained a key role in marine food webs for 400 million years and
      across varying physicochemical contexts, suggesting plasticity to environmental
      change. In this study, we investigated the biochemical effects of ocean
      acidification (OA) levels predicted for 2100 (pCO2 ~ 900 MUatm) on newly hatched
      tropical whitespotted bamboo sharks (Chiloscyllium plagiosum). Specifically, we
      measured lipid, protein, and DNA damage levels, as well as changes in the
      activity of antioxidant enzymes and non-enzymatic ROS scavengers in juvenile
      sharks exposed to elevated CO2 for 50 days following hatching. Moreover, we also
      assessed the secondary oxidative stress response, i.e., heat shock response and
      ubiquitin levels. Newly hatched sharks appear to cope with OA-related stress
      through a range of tissue-specific biochemical strategies, specifically through
      the action of antioxidant enzymatic compounds. Our findings suggest that ROS
      scavenging molecules, rather than complex enzymatic proteins, provide an
      effective defense mechanism in dealing with OA-elicited ROS formation. We argue
      that sharks' ancient antioxidant system, strongly based on non-enzymatic
      antioxidants (e.g., urea), may provide them with resilience towards OA,
      potentially beyond the tolerance of more recently evolved species, i.e.,
      teleosts. Nevertheless, previous research has provided evidence of detrimental
      effects of OA (interacting with other climate-related stressors) on some aspects
      of shark biology. Moreover, given that long-term acclimation and adaptive
      potential to rapid environmental changes are yet experimentally unaccounted for,
      future research is warranted to accurately predict shark physiological
      performance under future ocean conditions.

PMID- 29582346
TI  - Breast screening in symptomatic women over 35 years of age: improvements in
      service efficiency.
AB  - INTRODUCTION: The rationalization of cancer services in Ireland saw all women
      with symptomatic breast problems referred to one of the eight regional cancer
      centers. A pilot triaging system was introduced in St Vincent's University
      Hospital to streamline these services. Women over 35 years who do not meet urgent
      referral criteria are referred for a mammogram prior to a clinic appointment
      ("image first"). The aim of this study was to retrospectively determine the
      recall rates, biopsy rates, and rate of breast cancer identification within this
      cohort of patients. This was compared to a screening population of patients.
      METHODS: Patients triaged into the "image first" group within a one-year period
      were identified. Results of the initial mammogram, further imaging and subsequent
      biopsies were recorded. Data relating to number of recalls, number of patients
      biopsied and number of cancers identified within the Merrion Unit of the National
      Breastcheck Screening Program was obtained for comparison. RESULTS: One thousand
      six hundred eighty-eight referrals were triaged as "image first" over this
      period. 185 (11%) of patients required a biopsy of an identified lesion. Breast
      cancer was diagnosed in 65 patients (3.9%). During the same study period, of the
      42,099 women who were screened for breast cancer, 496 (1.8%) underwent biopsy and
      267 (0.63%) were diagnosed with breast cancer. CONCLUSION: Image first patients,
      who represent a cohort of "symptomatic" non-urgent women, have a greater rate of
      breast cancer detection than an asymptomatic screening population. This may have
      an impact on the appropriate triaging of symptomatic women in a national cancer
      center.

PMID- 29582347
TI  - In Vitro Assessment of Nasal Insufflation of Comminuted Drug Products Designed as
      Abuse Deterrent Using the Vertical Diffusion Cell.
AB  - In vitro evaluation of abuse deterrent formulations (ADFs) is a challenge since
      real abuse situations are variable and ADF technology is evolving. Specifically,
      an assessment of an ADF to deter nasal insufflation would be valuable. In this
      study, a vertical diffusion cell (VDC) was used to evaluate polyethylene oxide
      (PEO)-based tablets manipulated by three different forces. The commercially
      available products Oxycontin(r), an ADF, Opana(r), and metoprolol tartrate tablet
      formulations made in our laboratory were studied. Particle size distribution and
      percent recovery of manipulated tablets were measured. Grinding produced the
      lowest recovery and the smallest particle size distribution. Drug release was
      examined using a VDC by placing the dry comminuted particles on an enclosed
      wetted cellulose membrane. Dispensing dry particles on a VDC is atypical but
      includes some key features associated with an abuse situation where once the
      particles are snorted, the moisture in the nasal mucosa activates hydration and
      swelling of the polymers in the formulation, retarding drug release. Drug release
      from OxyContin(r), Opana(r), and metoprolol tablets were analyzed for the
      cutting, grinding, and milling modes of abuse. The analysis showed that in most
      cases, the mode of abuse produced different particle sizes with different release
      rates. Statistically different release rates were observed for metoprolol tablets
      made with different molecular weight PEO and with different porosities. These
      results indicate that within detection limits, the VDC can be used to quantitate
      release differences due to various modes of abuse used in this study.

PMID- 29582348
TI  - Comparison of detectability of breast cancer by abbreviated breast MRI based on
      diffusion-weighted images and postcontrast MRI.
AB  - PURPOSE: To compare the detectability of unenhanced abbreviated magnetic
      resonance imaging (MRI) based on diffusion-weighted imaging (DWI) and abbreviated
      postcontrast MRI for breast cancer. METHODS: The study population consisted of 87
      patients undergoing breast MRI between December 2016 and March 2017 in a clinical
      setting. All breast MRIs were performed using a 1.5-T MRI scanner with a 16
      channel breast radiofrequency coil. The abbreviated protocols based on DWI (AP1)
      and postcontrast MRI (AP2) were assessed independently by two radiologists.
      Sensitivity and specificity were calculated. Receiver operating characteristic
      analysis was performed and the areas under the curves (AUCs) were compared
      between AP1 and AP2. RESULTS: The study included 87 patients with 89 breast
      cancer lesions <= 2 cm in diameter. The sensitivity/specificity for AP1 and AP2
      for reader 1 was 89.9/97.6% and 95.5/90.6%, respectively, and those for reader 2
      was 95.5/94.1% and 98.9/94.1%, respectively. The AUCs for AP1 and AP2 for reader
      1 were 0.9629 and 0.9640 (p = 0.95), respectively, and those for reader 2 were
      0.9755 and 0.9843 (p = 0.46), respectively. CONCLUSIONS: The detectability of the
      unenhanced abbreviated protocol based on DWI would be comparable to that of
      abbreviated postcontrast MRI for breast cancer.

PMID- 29582349
TI  - Model reduction in mathematical pharmacology : Integration, reduction and linking
      of PBPK and systems biology models.
AB  - In this paper we present a framework for the reduction and linking of
      physiologically based pharmacokinetic (PBPK) models with models of systems
      biology to describe the effects of drug administration across multiple scales. To
      address the issue of model complexity, we propose the reduction of each type of
      model separately prior to being linked. We highlight the use of balanced
      truncation in reducing the linear components of PBPK models, whilst proper
      lumping is shown to be efficient in reducing typically nonlinear systems biology
      type models. The overall methodology is demonstrated via two example systems; a
      model of bacterial chemotactic signalling in Escherichia coli and a model of
      extracellular regulatory kinase activation mediated via the extracellular growth
      factor and nerve growth factor receptor pathways. Each system is tested under the
      simulated administration of three hypothetical compounds; a strong base, a weak
      base, and an acid, mirroring the parameterisation of pindolol, midazolam, and
      thiopental, respectively. Our method can produce up to an 80% decrease in
      simulation time, allowing substantial speed-up for computationally intensive
      applications including parameter fitting or agent based modelling. The approach
      provides a straightforward means to construct simplified Quantitative Systems
      Pharmacology models that still provide significant insight into the mechanisms of
      drug action. Such a framework can potentially bridge pre-clinical and clinical
      modelling - providing an intermediate level of model granularity between
      classical, empirical approaches and mechanistic systems describing the molecular
      scale.

PMID- 29582350
TI  - Root microbiota shift in rice correlates with resident time in the field and
      developmental stage.
AB  - Land plants in natural soil form intimate relationships with the diverse root
      bacterial microbiota. A growing body of evidence shows that these microbes are
      important for plant growth and health. Root microbiota composition has been
      widely studied in several model plants and crops; however, little is known about
      how root microbiota vary throughout the plant's life cycle under field
      conditions. We performed longitudinal dense sampling in field trials to track the
      time-series shift of the root microbiota from two representative rice cultivars
      in two separate locations in China. We found that the rice root microbiota varied
      dramatically during the vegetative stages and stabilized from the beginning of
      the reproductive stage, after which the root microbiota underwent relatively
      minor changes until rice ripening. Notably, both rice genotype and geographical
      location influenced the patterns of root microbiota shift that occurred during
      plant growth. The relative abundance of Deltaproteobacteria in roots
      significantly increased overtime throughout the entire life cycle of rice, while
      that of Betaproteobacteria, Firmicutes, and Gammaproteobacteria decreased. By a
      machine learning approach, we identified biomarker taxa and established a model
      to correlate root microbiota with rice resident time in the field (e.g.,
      Nitrospira accumulated from 5 weeks/tillering in field-grown rice). Our work
      provides insights into the process of rice root microbiota establishment.

PMID- 29582351
TI  - Comparing human peritoneal fluid and phosphate-buffered saline for drug delivery:
      do we need bio-relevant media?
AB  - An understanding of biological fluids at the site of administration is important
      to predict the fate of drug delivery systems in vivo. Little is known about
      peritoneal fluid; therefore, we have investigated this biological fluid and
      compared it to phosphate-buffered saline, a synthetic media commonly used for in
      vitro evaluation of intraperitoneal drug delivery systems. Human peritoneal fluid
      samples were analysed for electrolyte, protein and lipid levels. In addition,
      physicochemical properties were measured alongside rheological parameters.
      Significant inter-patient variations were observed with regard to pH (p < 0.001),
      buffer capacity (p < 0.05), osmolality (p < 0.001) and surface tension (p <
      0.05). All the investigated physicochemical properties of peritoneal fluid
      differed from phosphate-buffered saline (p < 0.001). Rheological examination of
      peritoneal fluid demonstrated non-Newtonian shear thinning behaviour and
      predominantly exhibited the characteristics of an entangled network. Inter
      patient and inter-day variability in the viscosity of peritoneal fluid was
      observed. The solubility of the local anaesthetic lidocaine in peritoneal fluid
      was significantly higher (p < 0.05) when compared to phosphate-buffered saline.
      Interestingly, the dissolution rate of lidocaine was not significantly different
      between the synthetic and biological media. Importantly, and with relevance to
      intraperitoneal drug delivery systems, the sustained release of lidocaine from a
      thermosensitive gel formulation occurred at a significantly faster rate into
      peritoneal fluid. Collectively, these data demonstrate the variation between
      commonly used synthetic media and human peritoneal fluid. The differences in drug
      release rates observed illustrate the need for bio-relevant media, which
      ultimately would improve in vitro-in vivo correlation.

PMID- 29582352
TI  - Correlation analysis of monocyte subsets and insulin resistance considering
      fetuin-A involvement in patients with type 2 diabetes.
AB  - BACKGROUND: Fetuin-A is a multifunctional circulating glycoprotein that can
      induce insulin resistance. Lately, adipose tissue has gained prominence as an
      effector site of fetuin-A. Although fetuin-A-induced proinflammatory polarization
      and migration of macrophages plays a crucial role, it remains obscure whether
      monocyte subsets in circulation could simulate characteristics of macrophages in
      adipose tissues. This study aims to investigate the correlation between monocyte
      subsets with fetuin-A and its relevant insulin resistance. RESULTS: We evaluated
      serum fetuin-A levels in 107 patients with type 2 diabetes (T2D). Using flow
      cytometry, we classified monocyte subsets into three subtypes: (a) classical,
      CD14++CD16-; (b) intermediate, CD14++CD16+, the most proinflammatory one; (c) and
      nonclassical, CD14+CD16++. We assessed the insulin resistance by the homeostasis
      model assessment for insulin resistance (HOMA-IR) in 68 patients without insulin
      injections. We observed no correlation between fetuin-A levels and classical (rho
      = - 0.005; P = 0.959), intermediate (rho = 0.022; P = 0.826), and nonclassical
      monocyte counts (rho = 0.063; P = 0.516), respectively. In addition, no
      significant correlation was found between log (HOMA-IR) and classical (rho =
      0.052; P = 0.688), intermediate (rho = 0.054; P = 0.676), and nonclassical
      monocyte counts (rho = 0.012; P = 0.353), respectively. However, serum fetuin-A
      levels showed positive correlation with log (HOMA-IR) (rho = 0.340; P = 0.007).
      Multiple regression analyses revealed a significant relationship between fetuin-A
      and log (HOMA-IR) (beta = 0.313; P = 0.016), but not with monocyte subsets.
      CONCLUSIONS: Monocyte subsets in circulation, including proinflammatory
      intermediate monocytes, were not associated with fetuin-A and insulin resistance.

PMID- 29582354
TI  - Repeat transcatheter aortic valve replacement using a 23 mm Evolut R in a small
      patient with a failed 20 mm SAPIEN XT.

PMID- 29582353
TI  - Development of apical hypertrophic cardiomyopathy with age in a transgenic mouse
      model carrying the cardiac actin E99K mutation.
AB  - In both humans and mice, the Glu-99-Lys (E99K) mutation in the cardiac actin gene
      (ACTC) results in little understood apical hypertrophic cardiomyopathy (AHCM). To
      determine how cross-bridge kinetics change with AHCM development, we applied
      sinusoidal length perturbations to skinned papillary muscle fibres from 2- and 5
      month old E99K transgenic (Tg) and non-transgenic (NTg) mice, and studied tension
      and its transients. These age groups were chosen because our preliminary studies
      indicated that AHCM develops with age. Fibres from 5-month old E99K mice showed
      significant decreases in tension, stiffness, the rate of the medium-speed
      exponential process and its magnitude compared to non-transgenic control. The
      nucleotide association constants increased with age, and they were significantly
      larger in E99K compared to NTg. However, there were no large differences in the
      rates of the cross-bridge detachment step, the rates of the force generation
      step, or the phosphate association constant. Our result on force/cross-bridge
      demonstrates that the decreased active tension of E99K fibres was caused by a
      decreased amount of force generated per each cross-bridge. The effects were
      generally less or insignificant at 2 months. A pCa-tension study showed increased
      Ca2+-sensitivity (pCa50) with age in both the E99K and NTg sample groups, and
      pCa50 was significantly larger (but only for 0.05-0.06 pCa units) in E99K than in
      NTg groups. A significant decrease in cooperativity (nH) was observed only in 5
      month old E99K mice. We conclude that the AHCM-causing ACTC E99K mutation is
      associated with progressive alterations in biomechanical parameters, with changes
      smaller at 2 months but larger at 5 months, correlating with the development of
      AHCM.

PMID- 29582355
TI  - Optimizing animal models for HIV-associated CNS dysfunction and CNS reservoir
      research.

PMID- 29582356
TI  - No reliable gene expression biomarkers of current or impending neurocognitive
      impairment in peripheral blood monocytes of persons living with HIV.
AB  - Events leading to and propagating neurocognitive impairment (NCI) in HIV-1
      infected (HIV+) persons are largely mediated by peripheral blood monocytes. We
      previously identified expression levels of individual genes and gene networks in
      peripheral blood monocytes that correlated with neurocognitive functioning in
      HIV+ adults. Here, we expand upon those findings by examining if gene expression
      data at baseline is predictive of change in neurocognitive functioning 2 years
      later. We also attempt to validate the original findings in a new sample of HIV+
      patients and determine if the findings are HIV specific by including HIV
      uninfected (HIV-) participants as a comparison group. At two time points,
      messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV-
      adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the
      Illumina HT-12 v4 Expression BeadChip. All participants received baseline and
      follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed
      using standard gene expression analysis and weighted gene co-expression network
      analysis with correction for multiple testing. Gene sets were analyzed for GO
      term enrichment. Only weak reproducibility of associations of single genes with
      neurocognitive functioning was observed, indicating that such measures are
      unreliable as biomarkers for HIV-related NCI; however, gene networks were
      generally preserved between time points and largely reproducible, suggesting that
      these may be more reliable. Several gene networks associated with variables
      related to HIV infection were found (e.g., MHC I antigen processing, TNF
      signaling, interferon gamma signaling, and antiviral defense); however, no
      significant associations were found for neurocognitive function. Furthermore,
      neither individual gene probes nor gene networks predicted later neurocognitive
      change. This study did not validate our previous findings and does not support
      the use of monocyte gene expression profiles as a biomarker for current or future
      HIV-associated neurocognitive impairment.

PMID- 29582357
TI  - Does time taken to achieve jaundice-clearance influence survival of the native
      liver in post-Kasai biliary atresia?
AB  - BACKGROUND: We reviewed the time taken for post-portoenterostomy (PE) biliary
      atresia (BA) patients to obtain jaundice-clearance (total bilirubin <= 1.2 mg/dL;
      JC) post-PE to determine if JC time (JCT) is prognostic for survival of the
      native liver (SNL). METHODS: The subjects were 66 BA patients treated with PE at
      our institute between 1989, the year when liver transplantation (LTx) became
      available in Japan, and 2014. JCT was used to create three groups (<= 30 days: n
      = 14; 31-60 days: n = 31; >= 61 days: n = 21). Medical records were reviewed
      retrospectively to evaluate: age at onset of symptoms, duration of symptoms pre
      PE, age and weight at PE, serum liver function tests, incidence of cholangitis,
      and micro-bile duct size at PE. RESULTS: Age at onset of symptoms, age and weight
      at PE, duration of symptoms pre-PE, and micro-bile duct size were similar for all
      patients in all three groups. JCT and SNL appeared to correlate because
      preoperative total bilirubin (7.1, 9.6, 10.2 mg/dL; P < 0.05) was significantly
      lower in the JCT <= 30 days group (P < 0.05) while there was a significant
      decrease in SNL (P < 0.03) and a significant increase in LTx (P < 0.01) in the
      JCT >= 61 days group. All LTx subjects who achieved JC were found to have
      developed cholangitis within 3 months of PE. CONCLUSION: During the follow-up of
      post-PE subjects, longer JCT and cholangitis occurrence within 3 months of PE
      would appear to be negative prognostic factors for SNL while preoperative total
      bilirubin would appear to be a positive prognostic factor for SNL.

PMID- 29582358
TI  - Follow-up after surgery for gastric cancer: how to do it.
AB  - There is no consensus on follow-up after gastric surgery for cancer, nor evidence
      that it improves outcomes. We investigated the impact of intensity of follow-up,
      comparing the regimens adopted by two centres, in Italy and in the UK. Patients
      who underwent surgery for gastric and junctional type-3 adenocarcinoma, between
      September 2009 and April 2013, at the Surgical Clinic, University of Brescia
      (Italy), and at the Department of Upper Gastrointestinal Surgery, University
      College London Hospital (UK), were identified. Patients' demographics, stage,
      recurrence rates, modality of detection and treatment were recorded. Overall
      survival and costs were compared between the two protocols. A total of 128
      patients were included. Recurrence rates were similar (p = 0.349), with more than
      70% diagnosed during regular follow-up appointments in both centres. At
      univariate and multivariate analysis, stage I and treatment of recurrence were
      associated with a better survival. Patients treated for recurrence at the Italian
      centre showed an almost significant better survival (p = 0.052). The intensive
      Italian surveillance protocol was associated with significant higher costs per
      year. Follow-up and early detection of recurrence did not affect survival in the
      analysed series, focused on periods in which chemotherapy was ineffective towards
      recurrence. However, intensive follow-up allowed a greater number of patients to
      receive a treatment for recurrence; this might prove useful in the next few
      years, when more effective chemotherapy combinations are expected to become
      available. The costs could be reduced by adopting a less intensive surveillance
      programme.

PMID- 29582359
TI  - Robotic versus standard open pancreatectomy: a propensity score-matched analysis
      comparison.
AB  - Interest in robotic pancreatectomy has been greatly increasing over the last
      decade. However, evidence supporting the benefits of robotic over open
      pancreatectomy is still outstanding. This study aims to assess the safety and
      efficacy of robotic pancreatectomy compared with the conventional open surgical
      approach. Propensity score-matched (1:1) was used to balance age, sex, BMI, ASA,
      tumor size, and malignancy of 17 robotic pancreaticoduodenectomies (PD), 12
      pancreatic enucleations (PE), and 28 distal pancreatectomies (DP); and was
      compared with the open standard approach. Robotic PD was associated with longer
      operative time (594 vs. 413 min; p = 0.03) and decreased blood loss (190 vs. 394
      ml; p = 0.001). Robotic PE showed a lower mean length of hospital stay (8.4 vs.
      12.8 days; p = 0.04) and, in addition, robotic DP showed less blood loss (175 vs.
      375 ml; p = 0.01), less severe morbidities (7.14 vs. 17.9%; p = 0.02), and a
      reduced mean length of hospital stay (8.9 vs. 15.1; p = 0.001). Overall,
      conversion rate was 4 (7%). Robotic pancreatectomy is as safe and effective as
      the standard open surgical approach with reduced blood loss in PD and DP, length
      of hospital stay in PE and DP, and severe morbidity in DP.

PMID- 29582360
TI  - Comparison of oropharyngeal leak pressure between the Ambu(r) AuraGainTM and the
      LMA(r) SupremeTM supraglottic airways: a randomized-controlled trial.
AB  - PURPOSE: Studies comparing the recently introduced Ambu(r) AuraGainTM (Auragain)
      with the LMA(r) SupremeTM (Supreme) supraglottic airway (SGA) have reported
      conflicting results regarding differences in oropharyngeal leak pressure (OLP).
      This randomized-controlled trial investigated the OLP of the Auragain compared
      with the Supreme in patients undergoing ambulatory surgery. METHODS: Adult
      patients with a body mass index <= 40 kg.m-2 presenting for ambulatory surgery
      and requiring an SGA were randomized to receive either the Auragain or the
      Supreme. Anesthesia was induced with lidocaine (1 mg.kg-1), fentanyl (1-2 MUg.kg
      1), and propofol (2-3 mg.kg-1). The SGA was inserted using a standard technique
      with the cuff inflated to 60 cmH2O. The groups were compared for the primary
      outcome of OLP. RESULTS: One hundred sixty-five patients (n = 81, Auragain; n =
      84, Supreme) completed the study. Demographics were similar between the groups.
      The mean (standard deviation [SD]) OLP was significantly higher in the Auragain
      than in the Supreme group [26.4 (2.8) cmH2O vs 21.6 (3.4) cmH2O, respectively;
      difference in means (MD), 4.8 cmH2O; 95% confidence interval (CI), 3.9 to 5.8; P
      < 0.001]. The mean (SD) insertion time was longer in the Auragain than in the
      Supreme group [13 (4) sec vs 11 (3) sec, respectively; MD, 2 sec; 95% CI, 1 to 3
      sec; P < 0.001]. CONCLUSION: In patients undergoing ambulatory anesthesia, the
      OLP was higher but took longer to insert with the Auragain than with the Supreme.
      A higher OLP may allow for SGAs to be utilized in a wider range of patients and
      procedures. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02816463). Registered
      28 June 2016.

PMID- 29582362
TI  - Impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features (NIFTP) on the risk of malignancy estimated by the ultrasonographic
      classification of the American Thyroid Association (ATA) in thyroid nodules >1
      cm.

PMID- 29582364
TI  - Primary Care Providers' Intended Use of Decision Aids for Prostate-Specific
      Antigen Testing for Prostate Cancer Screening.
AB  - Decision aids are tools intended to help people weigh the benefits and harms of a
      health decision. We examined primary care providers' perspective on use of
      decision aids and explored whether providers' beliefs and interest in use of a
      decision aid was associated with offering the prostate-specific antigen (PSA)
      test for early detection of prostate cancer. Data were obtained from 2016
      DocStyles, an annual, web-based survey of U.S. healthcare professionals including
      primary care physicians (n = 1003) and nurse practitioners (n = 253). We found
      that the majority of primary care providers reported not using (patient) decision
      aids for prostate cancer screening, but were interested in learning about and
      incorporating these tools in their practice. Given the potential of decision aids
      to guide in informed decision-making, there is an opportunity for evaluating
      existing decision aids for prostate cancer screening for clinical use.

PMID- 29582363
TI  - Electrophysiological characteristics and radiofrequency ablation of sustained
      monomorphic ventricular tachycardia in adult patients with isolated ventricular
      noncompaction.
AB  - PURPOSE: This study examined electrophysiological characteristics and outcomes of
      patients with sustained ventricular tachycardia (VT) in the setting of isolated
      ventricular noncompaction (IVNC). BACKGROUND: In patients with IVNC, VT has been
      associated with sudden cardiac death. However, the electrophysiological
      characteristics and optimal management of these VTs are only incompletely
      understood. METHODS: This retrospective cohort study assessed arrhythmia
      characteristics and outcomes in IVNC patients with sustained monomorphic VTs.
      Data were obtained from five academic centers covering the time period from
      January 1, 2006, to December 31, 2016, with a median follow-up of 40 months.
      RESULTS: Eighteen consecutive IVNC patients with sustained VTs (12 males [66%],
      mean age of 44.4 +/- 16.9 years) were enrolled. Seven (39%) patients underwent VT
      ablation (five males, mean age of 43.3 +/- 15.5 years) and nine (50%) patients
      received ICD therapy. Six of 18 patients (33%) died during a median follow-up of
      40 months. Of these, three had ICDs, two had undergone VT ablation, and one had
      received only antiarrhythmic drugs. Among the seven patients with prior VT
      ablation, five VTs in the RV (three RVOT and one tricuspid annulus) and two LV
      VTs (one anterolateral papillary muscle and one inferolateral wall) were
      localized by 3-D mapping and successfully ablated. In six of seven ablation cases
      (85.7%), the VTs were distant from the noncompaction zone. VTs appeared to be
      focal in 57% (4/7) and macro-reentry in 43% (3/7) of patients based on 3-D
      mapping and entrainment studies. The success rate of VT ablation was 85.7% with
      one VT recurrence and two deaths during the mean follow-up of 54 (28-115) months.
      CONCLUSIONS: IVNC Patients with sustained VTs appear to have a poor prognosis
      despite receiving ICD or apparently successful VT ablation therapy. Further, most
      VTs appear to arise remote from the noncompaction zone. Whether these VTs were
      "idiopathic" or related to IVNC was uncertain.

PMID- 29582365
TI  - Evaluation of Cardiovascular Toxicity Associated with Treatments Containing
      Proteasome Inhibitors in Multiple Myeloma Therapy.
AB  - INTRODUCTION: Recently new treatment options have substantially increased
      survival for patients with relapsed and/or refractory multiple myeloma (RRMM).
      Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib,
      offer high response rate and prolonged survival. These agents are generally well
      tolerated but demonstrated a significant cardiovascular toxicity, mostly for
      regimen containing carfilzomib. AIM: To assess the cardiovascular damage in
      patients treated with PI for RRMM. METHODS: 28 consecutive subjects treated with
      PI for RRMM were evaluated and compared with a population of 22 control (Con)
      subjects, matched for age, sex and mean 24 h blood pressure (24hMBP). All
      individuals underwent trans-thoracic echocardiography, ambulatory blood pressure
      monitoring and pulse wave velocity (PVW) study. RESULTS: PI patients did not have
      significant differences in blood pressure load and PWV compared to controls.
      Among echocardiographic parameters, the global longitudinal strain (GLS) was
      significantly decreased in PI subjects (p = 0.02). The GLS was significantly
      lower also considering only patients treated with carfilzomib. Moreover, among
      carfilzomib patients, we found increase values of left ventricle mass indexed by
      BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and
      morphological and functional parameters of LV, treatment with PI and carfilzomib
      were significantly associated with GLS (p = 0.01; p = 0.036, respectively).
      CONCLUSIONS: PI treatment is associated with subclinical LV dysfunction in
      patients with RRMM compared to controls, as demonstrated by lower GLS values.
      These results are confirmed also considering patients treated with carfilzomib.
      Moreover, in this subgroup of patients, the LVMi is also increased, suggesting
      higher cardiotoxicity with this treatment.

PMID- 29582367
TI  - ?

PMID- 29582366
TI  - The reversal effect of Ginsenoside Rh2 on drug resistance in human colorectal
      carcinoma cells and its mechanism.
AB  - Recent studies hint that Ginsenoside is involved in cancer prevention and
      treatment. In this study, we investigated the effect of Ginsenoside Rh2 on drug
      resistance in human colorectal carcinoma (CRC) cells and its mechanism. The
      resistance reversion effect of Ginsenoside Rh2 in CRC cells was analyzed using
      CCK-8 assay. After treating with Ginsenoside Rh2, the cell cycle distribution and
      cellular apoptosis were analyzed by flow cytometry, cell migration was determined
      by transwell migration assay, the expression of drug-resistance genes and
      proteins were evaluated using quantitative real-time polymerase chain reaction
      (qRT-PCR) and Western blot, respectively. Ginsenoside Rh2 could enhance the
      cytotoxicity of 5-FU in drug-resistant CRC cells (LoVo/5-FU and HCT-8/5-FU).
      Treatment with Ginsenoside Rh2 could result in an increase of cell numbers in
      G0/G1 phase accompanied with a decrease in S-phase, and induced cellular
      apoptosis in drug-resistant CRC cells. In addition, the migration process and EMT
      process of drug-resistant CRC cells were suppressed by treatment of Ginsenoside
      Rh2. Compared to control group, expression of drug-resistance genes, such as
      MRP1, MDR1, LRP and GST, were negatively correlated to Ginsenoside Rh2. All these
      results indicated that Ginsenoside Rh2 could effectively reverse drug resistance
      in human colorectal carcinoma cell and its mechanism involved the prevention of
      cellular proliferation and migration, the promotion of cellular apoptosis and the
      alteration of drug-resistance genes, which suggested that Ginsenoside Rh2 may act
      as a promising candidate for drug resistance in human colorectal carcinoma
      chemotherapy.

PMID- 29582369
TI  - Field Cancerization Therapies for Management of Actinic Keratosis: A Narrative
      Review.
AB  - Actinic keratoses (AKs) are atypical, precancerous proliferations of
      keratinocytes that develop because of chronic exposure to ultraviolet (UV)
      radiation. Treatment of AK can be lesion-directed or field-directed. Field
      cancerization theory postulates that the skin surrounding AK is also at increased
      risk for possible malignant transformation since it has been exposed to the same
      chronic UV light. Field-directed therapies thus have the potential to address
      subclinical damage, reduce AK recurrence rates, and potentially reduce the risk
      of squamous cell carcinoma (SCC) development. Published clinical studies have
      found lesion clearance rates ranging from 81 to 91% for photodynamic therapy
      (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL).
      Clinical studies have also been published on various topical treatments. Complete
      clinical clearance (CCC) was significantly higher in patients treated with a
      combination of 5-fluorouracil and salicylic acid (5-FU-SA) than in the vehicle
      group across multiple studies, and CCC ranged between 46 and 48% following
      treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS)
      found reduction in lesion sizes to range from 67 to 75%. Reported results have
      been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam,
      which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with
      ingenol mebutate were also significantly more effective than vehicle at clearing
      AK lesions. All treatments resulted in mild, localized skin reactions. PDT using
      conventional light sources was associated with increased severity of pain and/or
      discomfort, while PDT using daylight as the light source was associated with less
      pain and occasionally no pain at all. Though no widely accepted algorithm for the
      treatment of AKs exists, field-directed therapy can be particularly useful for
      treating photo-exposed areas containing multiple AKs. Additional research with
      more direct comparisons between these field-directed therapies will help
      clinicians determine the best therapeutic approach. Here, we provide a balanced
      and comprehensive narrative review of the literature, considering both light
      based and topical therapies with a focus on their field-therapy aspects, and
      propose a therapeutic algorithm for selecting an appropriate treatment in the
      clinical setting.

PMID- 29582368
TI  - Expression of kallikrein-related peptidase 13 is associated with poor prognosis
      in esophageal squamous cell carcinoma.
AB  - OBJECTIVE: Our previous differential transcriptome analysis between a paired
      specimen of normal and esophageal squamous cell carcinoma (ESCC) tissues found
      aberrant expression of kallikrein-related peptidase 13 (KLK13) in tumors. In this
      study, we evaluated the expression of KLK13 in many ESCC cases in relation with
      clinical features, and the prognosis. METHODS: Eighty-eight ESCC cases were
      subjected to immunohistological staining for KLK13 and classified into KLK13
      negative and KLK13-positive groups. Difference of clinical features and the
      prognosis between the groups was analyzed. RESULTS: In normal esophageal mucosa,
      KLK13 expression was evident but limited in the stratum granulosum in all cases.
      By contrast, only 27 of 88 ESCC samples showed KLK13 expression, whereas the
      remaining 61 tumors showed no KLK13 expression. The KLK13-positive group was
      significantly associated with pT classification (deeper tumor invasions; P =
      0.0282), pN classification (lymph node metastasis; P = 0.0163), and advanced TNM
      stage (P = 0.0198). In KLK13-positive samples, KLK13-expressing cells often
      expressed Ki67, a proliferation marker, unlike normal mucosa, in which Ki67
      expressing cells were limited to the basal layer and did not express KLK13.
      Compared with patients with KLK13-negative group, KLK13-positive group showed
      poorer postoperative prognosis. CONCLUSION: Relatively high levels of KLK13
      expression in ESCC were associated with cell proliferation and correlated with
      tumor progression, advanced cancer stage, and poor prognosis.

PMID- 29582370
TI  - Immunofluorescence Staining Protocols for Major Autophagy Proteins Including LC3,
      P62, and ULK1 in Mammalian Cells in Response to Normoxia and Hypoxia.
AB  - Immunofluorescence is an invaluable technique widely used in cell biology. This
      technique allows visualization of the subcellular distribution of different
      target proteins or organelles, by specific recognition of the antibody to the
      endogenous protein itself or to its antigen via the epitope. This technique can
      be used on tissue sections, cultured cells, or individual cells. Meanwhile,
      immunofluorescence can also be used in combination with non-antibody fluorescent
      staining, such as DAPI or fluorescent fusion proteins, e.g., GFP or YFP,
      etc.Autophagy is a catabolic pathway in which dysfunctional organelles and
      cellular components are degraded via lysosomes. During this process, cytoplasmic
      LC3 translocates to autophagosomal membranes. Therefore, cells undergoing
      autophagy can be identified by visualizing fluorescently labeled LC3 or other
      autophagy markers. Immunofluorescence is an important part of autophagy detection
      methods even if observation of the formation of autophagosome by transmission
      electron microscopy has become a gold standard for characterizing autophagy.By
      observing the immunofluorescence staining of some key autophagy proteins, we can
      intuitively evaluate the levels of autophagy in samples. Herein, this protocol
      describes the predominant method used for the research of autophagy, which mainly
      focuses on the immunofluorescence staining of cellular LC3, P62, and ULK1 in
      response to normoxia and hypoxia, by presenting the detailed materials required
      and methodology.

PMID- 29582371
TI  - Determining Inorganic and Organic Nitrogen.
AB  - Nitrogen (N) is one of the key nutrients for algal growth and is an integral part
      of many cellular components, for example in proteins. Being able to determine the
      inorganic and organic pools of N is consequently critical for algal cultivation.
      In this chapter we present the methods we use for determining dissolved inorganic
      nitrogen (DIN), dissolved organic nitrogen (DON), and particulate organic
      nitrogen (PON). The methods presented here for DIN rely on colorimetric methods
      and those of DON and PON on filtration and high temperature catalytic oxidation.

PMID- 29582372
TI  - Determining Dissolved and Biogenic Silica.
AB  - Most algae do not use silicon in any form with one notable exception, diatoms.
      Silicon is a major constituent of diatoms. Diatoms are characterized by high
      growth rates and are often one of the key groups in forming algal blooms in
      natural waters, and as such it is an interesting group for cultivation. In this
      chapter we present methods for determining dissolved silica (DSi) and biogenic
      silica (BSi), oxide forms of silicon, based on colorimetric methods. BSi is
      determined after filtration and alkaline digestion.

PMID- 29582373
TI  - Isolation and Enrichment of Newborn and Adult Skin Stem Cells of the
      Interfollicular Epidermis.
AB  - The interfollicular epidermis regenerates from a heterogeneous population of
      basal cells undergoing either self-renewal or terminal differentiation, thereby
      balancing cell loss in tissue turnover or in wound repair. In this chapter, we
      describe a reliable and simple method for isolating interfollicular epithelial
      stem cells from the skin of newborn mice or from tail and ear skin of adult mice
      using fluorescence-activated cell sorting (FACS). We also provide a detailed
      protocol for culturing interfollicular epidermal stem cells and to assess their
      proliferative potential and self-renewing ability. These techniques are useful
      for directly evaluating epidermal stem cell function in normal mice under
      different conditions or in genetically modified mouse models.

PMID- 29582374
TI  - Isolation and Cultivation of Epidermal (Stem) Cells.
AB  - Recent studies have shown that epidermal stem cells derived from the epidermis of
      are able to form hair follicles in the presence of hair follicle-inducing cells.
      Here we describe the method that we have used to isolate and cultivate epidermal
      stem cells.

PMID- 29582375
TI  - Identification of Human Cutaneous Squamous Cell Carcinoma Cancer Stem Cells.
AB  - Epithelia are under constant threat from environmental carcinogens and none more
      so than squamous epithelia, which form the outermost linings of our bodies. Hence
      malignancies of squamous epithelia are collectively the most common cancer type
      and with the highest mortality, despite a constant cell turnover and only
      relatively rare long-lived adult tissue stem cells. Genetic analysis from SCC
      whole genome sequencing reveals commonality in mutated genes, despite various
      etiological factors. Most SCC types have been shown to exhibit hierarchical
      growth, in which a high frequency of cancer stem cells is associated with poor
      prognosis. For human cutaneous SCC (cSCC), we have shown that cancer stem cells
      express CD133 and that this population can recreate tumor heterogeneity in a
      novel in vivo model. CD133+ cSCC cells is small subset of tumor cells (~1%) in
      the outer layer of cSCC that are highly enriched for tumor-initiating capacity
      (TIC) (~1/400) compared to unsorted cSCC cells (~1/106). Xenografts of CD133+
      cSCC recreated the original cSCC tumor histology and organizational hierarchy,
      while CD133- cells did not. Only CD133+ cells demonstrated the capacity for self
      renewal in serial transplantation studies. Hence, cSCC has the potential to be
      the ideal model in which to study SCC biology.

PMID- 29582376
TI  - Isolation, Culture, and Motility Measurements of Epidermal Melanocytes from GFP
      Expressing Reporter Mice.
AB  - In this article, we provide a method to isolate primary epidermal melanocytes
      from reporter mice, which also allow targeted gene inactivation. The mice from
      which these cells are isolated are bred into a Rosa26 mT/mG reporter background,
      which results in GFP expression in the targeted melanocytic cell population.
      These cells are isolated and cultured to >95% purity. The cells can be used for
      gene expression studies, clonogenic experiments, and biological assays, such as
      capacity for migration. Melanocytes are slow moving cells, and we also provide a
      method to measure motility using individual cell tracking and data analysis.

PMID- 29582377
TI  - Serial dependence in position occurs at the time of perception.
AB  - Observers perceive objects in the world as stable over space and time, even
      though the visual experience of those objects is often discontinuous and
      distorted due to masking, occlusion, camouflage, or noise. How are we able to
      easily and quickly achieve stable perception in spite of this constantly changing
      visual input? It was previously shown that observers experience serial dependence
      in the perception of features and objects, an effect that extends up to 15
      seconds back in time. Here, we asked whether the visual system utilizes an
      object's prior physical location to inform future position assignments in order
      to maximize location stability of an object over time. To test this, we presented
      subjects with small targets at random angular locations relative to central
      fixation in the peripheral visual field. Subjects reported the perceived location
      of the target on each trial by adjusting a cursor's position to match its
      location. Subjects made consistent errors when reporting the perceived position
      of the target on the current trial, mislocalizing it toward the position of the
      target in the preceding two trials (Experiment 1). This pull in position
      perception occurred even when a response was not required on the previous trial
      (Experiment 2). In addition, we show that serial dependence in perceived position
      occurs immediately after stimulus presentation, and it is a fast stabilization
      mechanism that does not require a delay (Experiment 3). This indicates that
      serial dependence occurs for position representations and facilitates the stable
      perception of objects in space. Taken together with previous work, our results
      show that serial dependence occurs at many stages of visual processing, from
      initial position assignment to object categorization.

PMID- 29582379
TI  - Author's Reply to Valenzuela et al.: Comment on "Drinking Strategies: Planned
      Drinking Versus Drinking to Thirst".

PMID- 29582378
TI  - Correction to: Test-Retest Reliability and Interpretation of Common Concussion
      Assessment Tools: Findings from the NCAA-DoD CARE Consortium.
AB  - The article Test-Retest Reliability and Interpretation of Common Concussion
      Assessment Tools.

PMID- 29582380
TI  - Comment on: "Drinking Strategies: Planned Drinking versus Drinking to Thirst".

PMID- 29582381
TI  - The Effect of Chronic Exercise Training on Leptin: A Systematic Review and Meta
      Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Leptin is a hormone associated with satiety, lipid oxidation, energy
      expenditure, and energy homeostasis. To date, the current body of research
      examining the effect of chronic exercise training on leptin has yielded
      inconsistent results. OBJECTIVE: The purpose of this meta-analysis was to provide
      a quantitative estimate of the magnitude of change in leptin levels following
      participation in exercise interventions lasting >= 2 weeks. METHODS: All studies
      included were peer-reviewed and published in English. To be included, studies
      randomized human participants to an exercise training group or non-exercise
      comparison group for an exercise training intervention. Leptin levels were
      measured at baseline, during, and/or after completion of the exercise training
      program. Random-effects models were used to aggregate a mean effect size (ES) and
      95% confidence intervals (CIs), and identify potential moderators. RESULTS:
      Seventy-two randomized controlled trials met the inclusion criteria and resulted
      in 107 effects (n = 3826). The mean ES of 0.24 (95% CI 0.16-0.32, p < 0.0001)
      indicated a decrease in leptin following an exercise training program. A decrease
      in %Fat (beta = - 0.07, p < 0.01) was associated with a decrease in leptin after
      accounting for the type of control group (beta = - 0.38, p < 0.0001) used in each
      study. CONCLUSION: These results suggest that engaging in chronic exercise
      training (>= 2 weeks) is associated with a decrease in leptin levels for
      individuals regardless of age and sex. However, a greater decrease in leptin
      occurred with a decreased percentage of body fat.

PMID- 29582382
TI  - Correction to: Power of Peer Support to Change Health Behavior to Reduce Risks
      for Heart Disease and Stroke for African American Men in a Faith-Based Community.
AB  - An error in Fig. 1 in this article as originally published ("Theme 6: feelings of
      belonging and being care for" was missing the numeral "6") has been corrected.
      The original article has been corrected.

PMID- 29582383
TI  - Factors Associated with Health Insurance Status in an Asian American Population
      in New York City: Analysis of a Community-Based Survey.
AB  - BACKGROUND: Immigrants comprise approximately 13% of the US population and 33%
      lack health coverage. Asian Americans are the fastest growing immigrant group;
      many lack a usual source of care. This study examines factors associated with
      health insurance among Asian American immigrants living in New York City.
      METHODS: Community needs assessments were conducted among Asian American
      subgroups in New York City from 2013 to 2015; analysis was completed in 2017 and
      2018. Descriptive statistics examined factors associated with health insurance
      status while stratifying by Asian ethnic subgroup; multivariable logistic
      regression models further assessed these associations (p < 0.05 significance
      level). RESULTS: Approximately 19% of the study population (n = 1399) was
      uninsured. Logistic regression models adjusted for all factors. Among East
      Asians, insurance status was associated with female sex (OR = 2.8, p = 0.005),
      excellent/very good health status (OR = 3.5, p = 0.014), and seeing a private
      doctor when sick or injured (OR = 3.2, p = 0.033). Among South Asians, insurance
      status was associated with high school/some college and college education (OR =
      2.6 and 2.9, respectively, p = 0.039 and p = 0.021), having a routine health
      check in the past year (OR = 6.4, p < 0.001), no diabetes diagnosis (OR = 2.7, p
      = 0.030), and a tuberculosis diagnosis (OR = 4.7, p = 0.019). Among Southeast
      Asians, insurance status was associated with less than high school education (p <
      0.05), living in the USA > 20 years (OR = 3.7, p = 0.009), having a routine
      health check in the past year (OR = 5.6, p = 0.025), and seeing a private doctor
      when sick or injured (OR = 2.6, p = 0.018). CONCLUSIONS: Health insurance status
      was associated with differing factors among each subgroup. Findings may inform
      strategies to address challenges and barriers of healthcare access to immigrants,
      making healthcare more accessible to this underserved population.

PMID- 29582385
TI  - 1H, 13C and 15N backbone resonance assignment of the lamin C-terminal region
      specific to prelamin A.
AB  - Lamins are the main components of the nucleoskeleton. They form a protein
      meshwork that underlies the inner nuclear membrane. Mutations in the LMNA gene
      coding for A-type lamins (lamins A and C) cause a large panel of human diseases,
      referred to as laminopathies. These diseases include muscular dystrophies,
      lipodystrophies and premature aging diseases. Lamin A exhibits a C-terminal
      region that is different from lamin C and is post-translationally modified. It is
      produced as prelamin A and it is then farnesylated, cleaved, carboxymethylated
      and cleaved again in order to become mature lamin A. In patients with the severe
      Hutchinson-Gilford progeria syndrome, a specific single point mutation in LMNA
      leads to an aberrant splicing of the LMNA gene preventing the post-translational
      processing of prelamin A. This leads to the accumulation of a permanently
      farnesylated lamin A mutant lacking 50 amino acids named progerin. We here report
      the NMR 1H, 15N, 13CO, 13Calpha and 13Cbeta chemical shift assignment of the C
      terminal region that is specific to prelamin A, from amino acid 567 to amino acid
      664. We also report the NMR 1H, 15N, 13CO, 13Calpha and 13Cbeta chemical shift
      assignment of the C-terminal region of the progerin variant, from amino acid 567
      to amino acid 614. Analysis of these chemical shift data confirms that both
      prelamin A and progerin C-terminal domains are largely disordered and identifies
      a common partially populated alpha-helix from amino acid 576 to amino acid 585.
      This helix is well conserved from fishes to mammals.

PMID- 29582384
TI  - NMR backbone assignments of the tyrosine kinase domain of human fibroblast growth
      factor receptor 3 in apo state and in complex with inhibitor PD173074.
AB  - Fibroblast growth factors receptors (FGFR) are transmembrane protein tyrosine
      kinases involved in many cellular process, including growth, differentiation and
      angiogenesis. Dysregulation of FGFR enzymatic activity is associated with
      developmental disorders and cancers; therefore FGFRs have become attractive
      targets for drug discovery, with a number of agents in late-stage clinical
      trials. Here, we present the backbone resonance assignments of FGFR3 tyrosine
      kinase domain in the ligand-free form and in complex with the canonical FGFR
      kinase inhibitor PD173074. Analysis of chemical shift changes upon inhibitor
      binding highlights a characteristic pattern of allosteric network perturbations
      that is of relevance for future drug discovery activities aimed at development of
      conformationally-selective FGFR inhibitors.

PMID- 29582386
TI  - Solution NMR assignment of the C-terminal domain of human chTOG.
AB  - The microtubule regulatory protein colonic and hepatic tumor overexpressed gene
      (chTOG), also known as cytoskeleleton associated protein 5 (CKAP5) plays an
      important role in organizing the cytoskeleton and in particular in the assembly
      of k-fibres in mitosis. Recently, we dissected the hitherto poorly understood C
      terminus of this protein by discovering two new domains-a cryptic TOG domain
      (TOG6) and a smaller, helical domain at the very C-terminus. It was shown that
      the C-terminal domain is important for the interaction with the TACC domain in
      TACC3 during the assembly of k-fibres in a ternary complex that also includes
      clathrin. Here we now present the solution NMR assignment of the chTOG C-terminal
      domain which confirms our earlier prediction that it is mainly made of alpha
      helices. However, the appearance of the 1H-15N HSQC spectrum is indicative of the
      presence of a considerable amount of unstructured and possibly flexible portions
      of protein in the domain.

PMID- 29582388
TI  - Action influences unconscious visual processing.
AB  - It has long been known that action is tightly linked to visual perception. In
      support of this connection, recent studies have shown that making a simple action
      towards a visual object can bias subsequent visual processing of features of the
      acted-on object. The present study examined whether conscious awareness of the
      acted-on object is necessary to yield this action effect. In two experiments, we
      found that making an action towards an invisible object resulted in greater
      priming in a subsequent visual search task. This shows that conscious awareness
      is not necessary to obtain the action-induced visual bias. More importantly, the
      result implies that action might amplify the sensory signal from the subliminally
      presented object, which is presumed to occur during early visual processing.

PMID- 29582387
TI  - Psychophysics with children: Investigating the effects of attentional lapses on
      threshold estimates.
AB  - When assessing the perceptual abilities of children, researchers tend to use
      psychophysical techniques designed for use with adults. However, children's
      poorer attentiveness might bias the threshold estimates obtained by these
      methods. Here, we obtained speed discrimination threshold estimates in 6- to 7
      year-old children in UK Key Stage 1 (KS1), 7- to 9-year-old children in Key Stage
      2 (KS2), and adults using three psychophysical procedures: QUEST, a 1-up 2-down
      Levitt staircase, and Method of Constant Stimuli (MCS). We estimated
      inattentiveness using responses to "easy" catch trials. As expected, children had
      higher threshold estimates and made more errors on catch trials than adults.
      Lower threshold estimates were obtained from psychometric functions fit to the
      data in the QUEST condition than the MCS and Levitt staircases, and the threshold
      estimates obtained when fitting a psychometric function to the QUEST data were
      also lower than when using the QUEST mode. This suggests that threshold estimates
      cannot be compared directly across methods. Differences between the procedures
      did not vary significantly with age group. Simulations indicated that
      inattentiveness biased threshold estimates particularly when threshold estimates
      were computed as the QUEST mode or the average of staircase reversals. In
      contrast, thresholds estimated by post-hoc psychometric function fitting were
      less biased by attentional lapses. Our results suggest that some psychophysical
      methods are more robust to attentiveness, which has important implications for
      assessing the perception of children and clinical groups.

PMID- 29582389
TI  - Memory guidance in distractor suppression is governed by the availability of
      cognitive control.
AB  - Information stored in the memory systems can affect visual search. Previous
      studies have shown that holding the to-be-ignored features of distractors in
      working memory (WM) could accelerate target selection. However, such facilitation
      effect was only observed when the cued to-be-ignored features remained unchanged
      within an experimental block (i.e., the fixed cue condition). No search benefit
      was obtained if the to-be-ignored features varied from trial to trial (i.e., the
      varied cue condition). In the present study, we conducted three behavioral
      experiments to investigate whether the WM and long-term memory (LTM)
      representations of the to-be-ignored features could facilitate visual search in
      the fixed cue (Experiment 1) and varied cue (Experiments 2 and 3) conditions.
      Given the importance of the processing time of cognitive control in distractor
      suppression, we divided visual search trials into five quintiles based on their
      reaction times (RTs) and examined the temporal characteristics of the suppression
      effect. Results showed that both the WM and LTM representations of the to-be
      ignored features could facilitate distractor suppression in the fixed cue
      condition, and the facilitation effects were evident across the quintiles in the
      RT distribution. However, in the varied cue condition, the RT benefits of the WM
      matched distractors occurred only in the trials with the longest RTs, whereas no
      advantage of the LTM-matched distractors was observed. These results suggest that
      the effective WM-guided distractor suppression depends on the availability of
      cognitive control and the LTM-guided suppression occurs only if sufficient WM
      resource is accessible by LTM reactivation.

PMID- 29582390
TI  - Effects of absolute luminance and luminance contrast on visual search in low
      mesopic environments.
AB  - Diverse adaptive visual processing mechanisms allow us to complete visual search
      tasks in a wide visual photopic range (>0.6 cd/m2). Whether search strategies or
      mechanisms known from this range extend below, in the mesopic and scotopic
      luminance spectra (<0.6 cd/m2), has yet to be addressed. Based on a study that
      addressed simple target discrimination in luminance environments using contrast
      dependent behavioral efficiency functions, we assessed visual search in more
      complex-feature and conjunction-search paradigms. The results verify the
      previously reported deficiency windows defined by an interaction of base
      luminance and luminance contrast for more complex visual-search tasks. Based on
      significant regression analyses, a more precise definition of the magnitude of
      contribution of different contrast parameters. Characterized feature search
      patterns had approximately a 2.5:1 ratio of contribution from the Michelson
      contrast property relative to Weber contrast, whereas the ratio was approximately
      1:1 in a serial-search condition. The results implicate near-complete
      magnocellular isolation in a visual-search paradigm that has yet to be
      demonstrated. Our analyses provide a new method of characterizing visual search
      and the first insight in its underlying mechanisms in luminance environments in
      the low mesopic and scotopic spectra.

PMID- 29582391
TI  - Authors' reply: Safety of Human Papillomavirus Vaccines.

PMID- 29582392
TI  - Benefit-Risk Monitoring of Vaccines Using an Interactive Dashboard: A
      Methodological Proposal from the ADVANCE Project.
AB  - INTRODUCTION: New vaccines are launched based on their benefit-risk (B/R) profile
      anticipated from clinical development. Proactive post-marketing surveillance is
      necessary to assess whether the vaccination uptake and the B/R profile are as
      expected and, ultimately, whether further public health or regulatory actions are
      needed. There are several, typically not integrated, facets of post-marketing
      vaccine surveillance: the surveillance of vaccination coverage, vaccine safety,
      effectiveness and impact. OBJECTIVE: With this work, we aim to assess the
      feasibility and added value of using an interactive dashboard as a potential
      methodology for near real-time monitoring of vaccine coverage and pre-specified
      health benefits and risks of vaccines. METHODS: We developed a web application
      with an interactive dashboard for B/R monitoring. The dashboard is demonstrated
      using simulated electronic healthcare record data mimicking the introduction of
      rotavirus vaccination in the UK. The interactive dashboard allows end users to
      select certain parameters, including expected vaccine effectiveness, age groups,
      and time periods and allows calculation of the incremental net health benefit
      (INHB) as well as the incremental benefit-risk ratio (IBRR) for different sets of
      preference weights. We assessed the potential added value of the dashboard by
      user testing amongst a range of stakeholders experienced in the post-marketing
      monitoring of vaccines. RESULTS: The dashboard was successfully implemented and
      demonstrated. The feedback from the potential end users was generally positive,
      although reluctance to using composite B/R measures was expressed. CONCLUSION:
      The use of interactive dashboards for B/R monitoring is promising and received
      support from various stakeholders. In future research, the use of such an
      interactive dashboard will be further tested with real-life data as opposed to
      simulated data.

PMID- 29582393
TI  - Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative
      Analysis of FAERS and CAERS Reporting Systems.
AB  - INTRODUCTION: Food supplements containing red yeast rice (RYR) are proposed as an
      alternative in statin-intolerant patients, although they actually contain natural
      statin(s) and their safety in clinical practice is still incompletely
      characterized. We described and compared adverse events (AEs) associated with RYR
      products submitted to reporting systems maintained by the Food and Drug
      Administration (FDA), with a focus on liver and muscular events. METHODS: We
      extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS)
      [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for
      Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004
      to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95%
      confidence interval (CI) calculation and case-by-case inspection were performed,
      with a focus on muscular and hepatic AEs. RESULTS: One thousand three hundred AEs
      were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas
      only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In
      FAERS, a large number of reports emerged for "general disorders and
      administration site conditions," whereas CAERS received also a high number of
      reports for "investigations" and "musculoskeletal and connective tissue
      disorders". Disproportionality analyses confirmed higher reporting of serious
      muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR =
      13.71; 95% CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44;
      5.44-13.10). CONCLUSIONS: Notwithstanding recognized limitations, these findings
      strengthen the importance of exploring multiple databases in safety assessment of
      RYR products, which should be monitored by clinicians for muscular and hepatic
      safety, and call for urgent review by policymakers to harmonize their regulatory
      status.

PMID- 29582394
TI  - Comparative Rates of Mortality and Serious Adverse Effects Among Commonly
      Prescribed Opioid Analgesics.
AB  - INTRODUCTION: The epidemic of prescription opioid overdose and mortality
      parallels the dispensing rates of prescription opioids, and the availability of
      increasingly potent opioid analgesics. OBJECTIVE: The common assumption that more
      potent opioid analgesics are associated with higher rates of adverse outcomes has
      not been adequately substantiated. We compared the rate of serious adverse events
      among commonly prescribed opioid analgesics of varying potency. METHODS: Serious
      adverse events (SAEs; defined as death, major medical effect, or hospitalization)
      resulting from exposure to tablets containing seven opioid analgesics (oxycodone,
      hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol)
      captured by the Researched Abuse, Diversion and Addiction-Related Surveillance
      (RADARS(r)) System Poison Center Program were evaluated from 2010 through 2016.
      Rates of SAEs were adjusted for availability through outpatient dispensing data
      and regressed on morphine milligram equivalents (MME). RESULTS: There were 19,480
      cases of SAE during the 7-year study period. Hydrocodone and oxycodone
      contributed to 77% of SAE cases. Comparing rates of outcome by relative potency,
      a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol
      (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold
      difference among individual opioid products. SAE rate and potency were related
      linearly-SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in
      MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency
      identified that MME comprised 96% of the variation observed. In contrast, potency
      did not explain variation seen using other study denominators (prescriptions
      dispensed, dosage units dispensed, and the number of individuals filling a
      prescription). CONCLUSIONS AND RELEVANCE: Potency of a prescription opioid
      analgesic demonstrates a significant, highly positive linear relationship with
      exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers.
      Potency should be carefully considered from both individual provider and public
      health perspectives.

PMID- 29582395
TI  - Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid-an
      Experimental Study.
AB  - The aim of this study was to evaluate in an experimental model of aortic valve
      (AV) stenosis the effectiveness of zoledronate on the inhibition of
      calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet
      for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to
      assess calcification. Thereafter, the AVs of eight animals were treated with
      local delivery of 500 MUg/l zoledronate. A placebo mixture was administered in
      the remaining eight animals. Standardized uptake values were corrected for blood
      pool activity, providing mean tissue to background ratios (TBRmean). In the
      zoledronate group, there was no progression of AV calcification (TBRmean 1.20 +/-
      0.12 vs 1.17 +/- 0.78,p = 0.29), while AV calcification progressed in the placebo
      group (1.22 +/- 0.15 vs 1.53 +/- 0.23,p = 0.006). Ascending aorta (AA)
      calcification progressed in both zoledronate and placebo groups. Histology
      confirmed the results of the PET/CT. Inhibition of AV calcification by local
      delivery of zoledronate is feasible and effective.

PMID- 29582396
TI  - The Effects of Non-selective Dopamine Receptor Activation by Apomorphine in the
      Mouse Hippocampus.
AB  - Apomorphine is a dopamine receptor agonist that activates D1-D5 dopamine
      receptors and that is used to treat Parkinson's disease (PD). However, the effect
      of apomorphine on non-motor activity has been poorly studied, and likewise, the
      effects of dopaminergic activation in brain areas that do not fulfill motor
      functions are unclear. The aim of this study was to determine how dopamine
      receptor activation affects behavior, as well as plasticity, morphology, and
      oxidative stress in the hippocampus. Adult mice were chronically administered
      apomorphine (1 mg/kg for 15 days), and the effects on memory and learning,
      synaptic plasticity, dendritic length, inflammatory responses, and oxidative
      stress were evaluated. Apomorphine impaired learning and long-term memory in
      mice, as evaluated in the Morris water maze test. In addition,
      electrophysiological recording of field excitatory postsynaptic potentials
      (fEPSP) indicated that the long-term potentiation (LTP) of synaptic transmission
      in the CA1 region of the hippocampus was fully impaired by apomorphine. In
      addition, a Sholl analysis of Golgi-Cox stained neurons showed that apomorphine
      reduced the total length of dendrites in the CA1 region of the hippocampus.
      Finally, there were more reactive astrocytes and oxidative stress biomarkers in
      mice administered apomorphine, as measured by GFAP immunohistochemistry and
      markers of redox balance, respectively. Hence, the non-selective activation of
      dopaminergic receptors in the hippocampus by apomorphine triggers deficiencies in
      learning and memory, it prevents LTP, reduces dendritic length, and provokes
      neuronal damage.

PMID- 29582397
TI  - Chronic Hippocampal Expression of Notch Intracellular Domain Induces Vascular
      Thickening, Reduces Glucose Availability, and Exacerbates Spatial Memory Deficits
      in a Rat Model of Early Alzheimer.
AB  - The specific roles of Notch in progressive adulthood neurodegenerative disorders
      have begun to be unraveled in recent years. A number of independent studies have
      shown significant increases of Notch expression in brains from patients at later
      stages of sporadic Alzheimer's disease (AD). However, the impact of Notch
      canonical signaling activation in the pathophysiology of AD is still elusive. To
      further investigate this issue, 2-month-old wild-type (WT) and hemizygous McGill
      R-Thy1-APP rats (Tg(+/-)) were injected in CA1 with lentiviral particles (LVP)
      expressing the transcriptionally active fragment of Notch, known as Notch
      Intracellular Domain (NICD), (LVP-NICD), or control lentivirus particles (LVP-C).
      The Tg(+/-) rat model captures presymptomatic aspects of the AD pathology,
      including intraneuronal amyloid beta (Abeta) accumulation and early cognitive
      deficits. Seven months after LVP administration, Morris water maze test was
      performed, and brains isolated for biochemical and histological analysis. Our
      results showed a learning impairment and a worsening of spatial memory in LVP
      NICD- as compared to LVP-C-injected Tg(+/-) rats. In addition, immuno
      histochemistry, ELISA multiplex, Western blot, RT-qPCR, and 1H-NMR spectrometry
      of cerebrospinal fluid (CSF) indicated that chronic expression of NICD promoted
      hippocampal vessel thickening with accumulation of Abeta in brain
      microvasculature, alteration of blood-brain barrier (BBB) permeability, and a
      decrease of CSF glucose levels. These findings suggest that, in the presence of
      early Abeta pathology, expression of NICD may contribute to the development of
      microvascular abnormalities, altering glucose transport at the BBB with impact on
      early decline of spatial learning and memory.

PMID- 29582398
TI  - The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in
      the Cerebral Cortex of Female Mice After a Stab Wound Injury.
AB  - Previous studies have shown that estradiol reduces reactive gliosis after a stab
      wound injury in the cerebral cortex. Since the therapeutic use of estradiol is
      limited by its peripheral hormonal effects, it is of interest to determine
      whether synthetic estrogenic compounds with tissue-specific actions regulate
      reactive gliosis. Tibolone is a synthetic steroid that is widely used for the
      treatment of climacteric symptoms and/or the prevention of osteoporosis. In this
      study, we have assessed the effect of tibolone on reactive gliosis in the
      cerebral cortex after a stab wound brain injury in ovariectomized adult female
      mice. By 7 days after brain injury, tibolone reduced the number of glial
      fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized
      calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the
      number of microglial cells with a reactive phenotype in comparison to vehicle
      injected animals. These effects on gliosis were associated with a reduction in
      neuronal loss in the proximity to the wound, suggesting that tibolone exerts
      beneficial homeostatic actions in the cerebral cortex after an acute brain
      injury.

PMID- 29582399
TI  - Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical
      or Cellular Losses.
AB  - Perinatal asphyxia remains a significant cause of neonatal mortality and is
      associated with long-term neurodegenerative disorders. In the present study, we
      evaluated cellular and subcellular damages to brain development in a model of
      mild perinatal asphyxia. Survival rate in the experimental group was 67%. One
      hour after the insult, intraperitoneally injected Evans blue could be detected in
      the fetuses' brains, indicating disruption of the blood-brain barrier. Although
      brain mass and absolute cell numbers (neurons and non-neurons) were not reduced
      after perinatal asphyxia immediately and in late brain development, subcellular
      alterations were detected. Cortical oxygen consumption increased immediately
      after asphyxia, and remained high up to 7 days, returning to normal levels after
      14 days. We observed an increased resistance to mitochondrial membrane
      permeability transition, and calcium buffering capacity in asphyxiated animals
      from birth to 14 days after the insult. In contrast to ex vivo data,
      mitochondrial oxygen consumption in primary cell cultures of neurons and
      astrocytes was not altered after 1% hypoxia. Taken together, our results
      demonstrate that although newborns were viable and apparently healthy, brain
      development is subcellularly altered by perinatal asphyxia. Our findings place
      the neonate brain mitochondria as a potential target for therapeutic protective
      interventions.

PMID- 29582402
TI  - Association of Herpes Viral Infections, Antiherpetic Therapy, and Dementia: Real
      or Alternative Fact?

PMID- 29582400
TI  - Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits
      Neuroprotective Effects in Dystrophic Neurons.
AB  - We have previously shown that inadequate dystrophin in cortical neurons in mdx
      mice is associated with age-dependent dyshomeostasis of resting intracellular
      Ca2+ ([Ca2+]i) and Na+ ([Na+]i), elevated reactive oxygen species (ROS)
      production, increase in neuronal damage and cognitive deficit. In this study, we
      assessed the potential therapeutic properties of the whole body periodic
      acceleration (pGz) to ameliorate the pathology observed in cortical neurons from
      the mdx mouse. pGz adds small pulses to the circulation, thereby increasing
      pulsatile shear stress to the vascular endothelium, which in turn increases
      production of nitric oxide (NO). We found [Ca2+]i and [Na+]i overload along with
      reactive oxygen species (ROS) overproduction in mdx neurons and cognitive
      dysfunction. mdx neurons showed increased activity of superoxide dismutase,
      glutathione peroxidase, malondialdehyde, and calpain as well as decreased cell
      viability. mdx neurons were more susceptible to hypoxia-reoxygenation injury than
      WT. pGz ameliorated the [Ca2+]i, and [Na+]i elevation and ROS overproduction and
      further increased the activities of superoxide dismutase, glutathione peroxidase
      and reduced the malondialdehyde and calpains. pGz diminished cell damage and
      elevated [Ca2+]i during hypoxia-reoxygenation and improved cognitive function in
      mdx mice. Moreover, pGz upregulated the expression of utrophin, dystroglycan-beta
      and CAPON, constitutive nitric oxide synthases, prosaposin, brain-derived
      neurotrophic, and glial cell line-derived neurotrophic factors. The present study
      demonstrated that pGz is an effective therapeutic approach to improve mdx neurons
      function, including cognitive functions.

PMID- 29582401
TI  - TRPV4: a Sensor for Homeostasis and Pathological Events in the CNS.
AB  - Transient receptor potential vanilloid type 4 (TRPV4) was originally described as
      a calcium-permeable nonselective cation channel. TRPV4 is now recognized as a
      polymodal ionotropic receptor: it is a broadly expressed, nonselective cation
      channel (permeable to calcium, potassium, magnesium, and sodium) that plays an
      important role in a multitude of physiological processes. TRPV4 is involved in
      maintaining homeostasis, serves as an osmosensor and thermosensor, can be
      activated directly by endogenous or exogenous chemical stimuli, and can be
      activated or sensitized indirectly via intracellular signaling pathways.
      Additionally, TRPV4 is upregulated in a variety of pathological conditions. In
      this review, we focus on the role of TRPV4 in mediating homeostasis and
      pathological events in the central nervous system (CNS). This review is composed
      of three parts. Section 1 describes the role of TRPV4 in maintaining homeostatic
      processes, including the volume of body water, ionic concentrations, volume, and
      the temperature. Section 2 describes the effects of activation and inhibition of
      TRPV4 in the CNS. Section 3 focuses on the role of TRPV4 during pathological
      events in CNS.

PMID- 29582403
TI  - Medications and Prescribing Patterns as Factors Associated with Hospitalizations
      from Long-Term Care Facilities: A Systematic Review.
AB  - BACKGROUND: Residents of long-term care facilities (LTCFs) are at high risk of
      hospitalization. Medications are a potentially modifiable risk factor for
      hospitalizations. OBJECTIVE: Our objective was to systematically review the
      association between medications or prescribing patterns and hospitalizations from
      LTCFs. METHODS: We searched MEDLINE, Embase, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL) and International Pharmaceutical Abstracts
      (IPA) from inception to August 2017 for longitudinal studies reporting
      associations between medications or prescribing patterns and hospitalizations.
      Two independent investigators completed the study selection, data extraction and
      quality assessment using the Joanna Briggs Institute Critical Appraisal Tools.
      RESULTS: Three randomized controlled trials (RCTs), 22 cohort studies, five case
      control studies, one case-time-control study and one case-crossover study,
      investigating 13 different medication classes and two prescribing patterns were
      included. An RCT demonstrated that high-dose influenza vaccination reduced all
      cause hospitalization compared with standard-dose vaccination (risk ratio [RR]
      0.93; 95% confidence interval [CI] 0.88-0.98). Another RCT found no difference in
      hospitalization rates between oseltamivir as influenza treatment and oseltamivir
      as treatment plus prophylaxis (treatment = 4.7%, treatment and prophylaxis =
      3.5%; p = 0.7). The third RCT found no difference between multivitamin/mineral
      supplementation and hospitalization (odds ratio [OR] 0.94; 95% CI 0.74-1.20) or
      emergency department visits (OR 1.05; 95% CI 0.76-1.47). Two cohort studies
      demonstrated influenza vaccination reduced hospitalization. Four studies
      suggested polypharmacy and potentially inappropriate medications (PIMs) increased
      all-cause hospitalization. However, associations between polypharmacy (two
      studies), PIMs (one study) and fall-related hospitalizations were inconsistent.
      Inconsistent associations were found between psychotropic medications with all
      cause and cause-specific hospitalizations (11 studies). Warfarin, nonsteroidal
      anti-inflammatory drugs, pantoprazole and vinpocetine but not long-term
      acetylsalicylic acid (aspirin), statins, trimetazidine, digoxin or beta-blockers
      were associated with all-cause or cause-specific hospitalizations in single
      studies of specific resident populations. Most cohort studies assessed prevalent
      rather than incident medication exposure, and no studies considered time-varying
      medication use. CONCLUSION: High-quality evidence suggests influenza vaccination
      reduces hospitalization. Polypharmacy and PIMs are consistently associated with
      increased all-cause hospitalization.

PMID- 29582405
TI  - Ixazomib for Relapsed or Refractory Multiple Myeloma: Review from an Evidence
      Review Group on a NICE Single Technology Appraisal.
AB  - Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide
      plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple
      myeloma. As part of a single technology appraisal (ID807) undertaken by the
      National Institute of Health and Care Excellence, the Evidence Review Group,
      Warwick Evidence was invited to independently review the evidence submitted by
      the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical
      effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized
      controlled trial in which 771 patients with relapsed or refractory multiple
      myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-,
      or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX
      using a de-novo partitioned-survival model with three health states (pre
      progression, post-progression, and dead). In their first submission, this model
      was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus
      dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX
      in third-line treatment. To estimate the relative clinical performance of IXA-LEN
      DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes.
      The network meta-analysis for overall survival was found to be flawed in several
      respects, but mainly because a hazard ratio input for one of the studies in the
      network had been inverted, resulting in a large inflation of the claimed
      superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its
      cost effectiveness. In subsequent submissions, Takeda withdrew second-line
      treatment as an option for IXA-LEN-DEX. The manufacturer's first submission
      comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1
      data from third- and fourth-line patients as proxy for a third-line population.
      The appraisal committee did not consider this reasonable because randomization in
      Tourmaline-MM1 was stratified according to one previous treatment and two or more
      previous treatments. A further deficiency was considered to be the manufacturer's
      use of interim survival data rather than the most mature data available. A second
      submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or
      fourth-line treatment (the two or more previous lines population) and a new
      patient access scheme was introduced. Covariate modeling of survival outcomes was
      proposed using the most mature survival data. The Evidence Review Group's main
      criticisms of the new evidence included: the utility associated with the pre
      progression health state was overestimated, treatment costs of ixazomib were
      underestimated, survival models were still associated with great uncertainty,
      leading to clinically implausible anomalies and highly variable incremental cost
      effectiveness ratio estimates, and the company had not explored a strong
      assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully
      maintained for a further 22 years beyond the observed data, which encompassed
      only approximately 2.5 years of observation. The appraisal committee remained
      unconvinced that ixazomib represented a cost-effective use of National Health
      Service resources. Takeda's third submission offered new base-case parametric
      models for survival outcomes, a new analysis of utilities, and proposed a
      commercial access agreement. In a brief critique of the third submission, the
      Evidence Review Group agreed that the selection of appropriate survival models
      was problematic and at the request of the National Institute for Health Care and
      Excellence investigated external sources of evidence regarding survival outcomes.
      The Evidence Review Group considered that some cost and utility estimates in the
      submission may have remained biased in favor of ixazomib. As a result of their
      third appraisal meeting, the committee judged that for the two to three prior
      therapies population, and at the price agreed in a commercial access agreement,
      ixazomib had the potential to be cost effective. It was referred to the Cancer
      Drugs Fund so that further data could accrue with the aim of diminishing the
      clinical uncertainties.

PMID- 29582404
TI  - Newer Antiepileptic Drugs for Status Epilepticus in Adults: What's the Evidence?
AB  - Status epilepticus (SE) is one of the most frequent neurological emergencies.
      Despite this, understanding of its pathophysiology and evidence regarding its
      management is limited. Rapid, effective, and well-tolerated treatment to achieve
      seizure cessation is advocated to prevent brain damage or potentially lethal
      outcomes. The last two decades have witnessed an exponential increase in the
      number of available antiepileptic drugs (AEDs). These compounds, especially
      lacosamide and levetiracetam, in view of their intravenous formulation, have been
      increasingly prescribed in SE. These and other newer AEDs present a promising
      profile in terms of tolerability, with few centrally depressive effects,
      favorable pharmacokinetic properties, and fewer drug interactions than classical
      AEDs; conversely, they are more expensive. There is still no clear evidence to
      suggest a specific beneficial impact of newer AEDs on SE outcome, preventing any
      strong recommendation regarding their prescription in SE. Further comparative
      studies are urgently required to clarify their place and optimal use in the
      armamentarium of SE treatment.

PMID- 29582406
TI  - Reslizumab for Treating Asthma with Elevated Blood Eosinophils Inadequately
      Controlled by Inhaled Corticosteroids: An Evidence Review Group Perspective of a
      NICE Single Technology Appraisal.
AB  - As part of the National Institute for Health and Care Excellence (NICE) Single
      Technology Appraisal (STA) process, the manufacturer of reslizumab (Teva)
      submitted evidence for its clinical and cost effectiveness for the treatment of
      eosinophilic asthma inadequately controlled by inhaled corticosteroids. NICE
      commissioned Southampton Health Technology Assessments Centre (SHTAC) as an
      independent Evidence Review Group (ERG) to provide a critique of the
      manufacturer's submitted evidence. Reslizumab is compared with best standard of
      care and omalizumab, for a small 'overlap' population of patients who have both
      eosinophilic and IgE-mediated severe asthma. This paper provides a summary of the
      ERG's review of the manufacturer's submission, and summarises the NICE Appraisal
      Committee's subsequent guidance (issued in August 2017). The ERG considered that
      there were limitations in the approach proposed by the manufacturer for the
      exacerbation rate and the utility for severe exacerbation. The company amended
      their initial analysis, following comments from the ERG and the NICE committee,
      whereby the incremental cost effectiveness ratio was L29,870 per QALY gained for
      reslizumab compared with best standard care. The NICE Appraisal Committee (AC)
      concluded that reslizumab was recommended as an option for the treatment of
      severe eosinophilic asthma that is inadequately controlled in adults despite
      maintenance therapy with high-dose inhaled corticosteroids plus another drug,
      only if (1) the blood eosinophil count has been recorded as 400 cells per
      microlitre or more and (2) the patient has had three or more asthma exacerbations
      in the past 12 months, and (3) the company provides reslizumab with the discount
      agreed in the patient access scheme.

PMID- 29582407
TI  - In vitro activity of linezolid, daptomycin and N-acetylcysteine agents on
      Staphylococcus aureus biofilms in the ventriculoperitoneal shunt model.
AB  - AIM: In this study, the effect of N-acetylcysteine (NAC) alone and in combination
      with linezolid (LIN) and daptomycin (DAPT) was examined on methicillin-sensitive
      Staphylococcus aureus (MSSA) biofilm formation. MATERIAL AND METHODS: Twelve
      groups (each containing six molds) of standard ventriculoperitoneal shunts were
      infected with MSSA. By using microbiological and electron microscopic evaluation
      methods, NAC was evaluated, alone and in combination with DAPT and LIN, in terms
      of preventing and eliminating biofilm capacity. The effect of NAC alone and in
      combination with DAPT and LIN were shown by microbial counts and electron
      microscopic observation. RESULTS: The results showed no significant difference in
      biofilm formation in shunts after different antibiotic treatments. However, the
      combination of NAC and DAPT had the highest bactericidal effects of all the
      groups. CONCLUSION: The resistance of bacteria and the dose-dependent effects of
      antibiotics can be considered.

PMID- 29582408
TI  - Strategies for the prevention of postoperative pulmonary complications.

PMID- 29582409
TI  - EphA2 receptor is a key player in the metastatic onset of Ewing sarcoma.
AB  - Ewing sarcoma (ES) is the second most common bone malignancy affecting children
      and young adults with poor prognosis due to high metastasis incidence. Our group
      previously described that EphA2, a tyrosine kinase receptor, promotes
      angiogenesis in Ewing sarcoma (ES) cells via ligand-dependent signaling. Now we
      wanted to explore EphA2 ligand-independent activity, controlled upon
      phosphorylation at S897 (p-EphA2S897 ), as it has been linked to metastasis in
      several malignancies. By reverse genetic engineering we explored the phenotypic
      changes after EphA2 removal or reintroduction. Gene expression microarray was
      used to identify key players in EphA2 signaling. Mice were employed to reproduce
      metastatic processes from orthotopically implanted engineered cells. We
      established a correlation between ES cells aggressiveness and p-EphA2S897 .
      Moreover, stable overexpression of EphA2 in low EphA2 expression ES cells
      enhanced proliferation and migration, but not a non-phosphorylable mutant
      (S987A). Consistently, silencing of EphA2 reduced tumorigenicity, migration and
      invasion in vitro, and lung metastasis incidence in experimental and spontaneous
      metastasis assays in vivo. A gene expression microarray revealed the implication
      of EphA2 in cell signaling, cellular movement and survival. ADAM19 knockdown by
      siRNA technology strongly reproduced the negative effects on cell migration
      observed after EphA2 silencing. Altogether, our results suggest that p-EphA2S897
      correlates with aggressiveness in ES, so blocking its function may be a promising
      treatment.

PMID- 29582410
TI  - National Prescribing Trends for High-Risk Anticholinergic Medications in Older
      Adults.
AB  - OBJECTIVES: To estimate prescribing tends of and correlates independently
      associated with high-risk anticholinergic prescriptions in adults aged 65 and
      older in office-based outpatient visits. DESIGN: Repeated cross-sectional
      analysis. SETTING: National Ambulatory Medical Care Survey (NAMCS). PARTICIPANTS:
      A national sample of office-based physician visits by adults aged 65 and older
      from 2006 to 2015 (n=96,996 unweighted). MEASUREMENTS: Prescriptions of high-risk
      anticholinergics, regardless of indication, were identified, and overall
      prescribing trends were estimated from 2006 to 2015. Stratified analyses of
      prescribing trends according to physician specialty and anticholinergic drug
      class were also performed. We used a multivariable logistic regression analysis
      to estimate the odds of high-risk anticholinergic prescription. RESULTS: Between
      2006 and 2015, a high-risk anticholinergic prescription was listed for 5,876
      (6.2%) 96,996 visits of older adults, representative of 14.6 million total visits
      nationally. The most common drug classes were antidepressants, antimuscarinics,
      and antihistamines, which accounted for more than 70% of prescribed
      anticholinergics. Correlates independently associated with greater odds of
      receiving a high-risk anticholinergic prescription were female sex, the Southern
      geographic region, specific physician specialties (e.g., psychiatry, urology),
      receipt of 6 or more concomitantly prescribed medications, and related clinical
      diagnoses (e.g., urinary continence) (p<.01 for all). CONCLUSION: The prevalence
      of high-risk anticholinergic prescriptions was stable over time but varied
      according to physician specialty and drug class. Quality prescribing should be
      promoted because safer alternatives are available.

PMID- 29582411
TI  - Influence of endometrial thickness on pregnancy rates in modified natural cycle
      frozen-thawed embryo transfer.
AB  - INTRODUCTION: Pregnancy after frozen-thawed embryo transfer (FET) is a
      multifactorial process. Although embryo quality is a key factor in determining
      pregnancy, other factors, including maternal determinants, are also considered to
      be predictive. Even though an association between endometrial thickness measured
      by transvaginal ultrasound and pregnancy rates has been reported in patients
      undergoing various assisted reproductive technology treatments, whether
      endometrial thickness predicts achieving pregnancy after natural cycle FET (NC
      FET) remains unclear. MATERIAL AND METHODS: In this cohort study, 463 patients
      allocated to the modified NC-FET (mNC-FET) arm of a previously published
      randomized controlled trial were included. Monitoring in mNC-FET cycles consisted
      of regular ultrasound scans, measuring both dominant follicle and endometrial
      thickness. When the dominant follicle reached a size of 16-20 mm, an injection of
      human chorionic gonadotrophin was administered and embryo thawing and transfer
      planned. No minimal endometrial thickness was defined below which transfer was to
      be deferred. The primary endpoint was ongoing pregnancy rate. RESULTS: Overall,
      the ongoing pregnancy rate per started FET cycle was 12.5%. Multivariate
      regression analyses showed that embryo quality was the only significant predictor
      for ongoing pregnancy. Mean endometrial thickness did not differ between patients
      achieving ongoing pregnancy and those who did not (9.0 vs. 8.8 mm, p = 0.4).
      Comparable results were obtained with regard to clinical pregnancy, live birth
      and miscarriage rates. The area under the receiver operator curve was 0.5,
      indicating little discriminatory value of endometrial thickness. CONCLUSIONS:
      Given that endometrial thickness was not found to be predictive of pregnancy
      after mNC-FET, cancellation based on endometrial thickness alone may not be
      justified.

PMID- 29582412
TI  - Diabetes and smoking as predictors of cancer in Indigenous adults from rural and
      remote communities of North Queensland - A 15-year follow up study.
AB  - Indigenous Australians generally have a poor health status and an elevated cancer
      mortality that has increased in recent decades. A cohort of 2,273 Aboriginal and
      Torres Strait Islander (TSI) adults (18+ years) from 26 remote communities in far
      North Queensland, who were initially free of cancer, were followed-up for an
      average of 15 years. The associations of baseline anthropometric, biochemical and
      behavioural factors with cancer incidence were investigated using competing risk
      survival analysis. The age-standardised incidence (all cancers) was 5.2
      cases/1,000 person-years (pys) (95% CI 4.1-6.6). Liver/bile duct and lung were
      the most common cancer sites. Overall cancer incidence was significantly higher
      in TSIs than Aboriginal people. The baseline prevalence of diabetes was 15.6% in
      Aboriginal and 25.6% in TSI people. The smoking rate of 59.8% for Aboriginal
      people was higher than the rate of 45.2% for TSIs. At follow-up, the adjusted sub
      hazard ratios (SHRs) of diabetes for all cancers combined were 1.8 (95% CI, 1.3
      2.6), and for digestive system cancers, 2.3 (95% CI, 1.2-4.4). Smokers had a 60%
      higher risk (SHR 1.6, 95% CI: 1.1-2.0) for all cancers combined and a fourfold
      risk (SHR 3.7, 95% CI 1.7-8.0) for lung cancers when compared to non-smokers,
      regardless of age, sex and ethnicity. The most common cancers encountered by this
      Indigenous cohort and their consequences are potentially preventable in
      Indigenous Australians by effective management of highly prevalent modifiable
      risks in primary service settings, screening participation and arranging for good
      access to treatment services.

PMID- 29582413
TI  - Dietary docosahexaenoic acid supplementation enhances expression of fatty acid
      binding protein 5 at the blood-brain barrier and brain docosahexaenoic acid
      levels.
AB  - The cytoplasmic trafficking of docosahexaenoic acid (DHA), a cognitively
      beneficial fatty acid, across the blood-brain barrier (BBB) is governed by fatty
      acid-binding protein 5 (FABP5). Lower levels of brain DHA have been observed in
      Alzheimer's disease (AD), which is associated with diminished BBB expression of
      FABP5. Therefore, up-regulating FABP5 expression at the BBB may be a novel
      approach for enhancing BBB transport of DHA in AD. DHA supplementation has been
      shown to be beneficial in various mouse models of AD, and therefore, the aim of
      this study was to determine whether DHA has the potential to up-regulate the BBB
      expression of FABP5, thereby enhancing its own uptake into the brain. Treating
      human brain microvascular brain endothelial (hCMEC/D3) cells with the maximum
      tolerable concentration of DHA (12.5 MUM) for 72 h resulted in a 1.4-fold
      increase in FABP5 protein expression. Associated with this was increased
      expression of fatty acid transport proteins 1 and 4. To study the impact of
      dietary DHA supplementation, 6- to 8-week-old C57BL/6 mice were fed with a
      control diet or a DHA-enriched diet for 21 days. Brain microvascular FABP5
      protein expression was up-regulated 1.7-fold in mice fed the DHA-enriched diet,
      and this was associated with increased brain DHA levels (1.3-fold). Despite an
      increase in brain DHA levels, reduced BBB transport of 14 C-DHA was observed over
      a 1 min perfusion, possibly as a result of competitive binding to FABP5 between
      dietary DHA and 14 C-DHA. This study has demonstrated that DHA can increase BBB
      expression of FABP5, as well as fatty acid transporters, overall increasing brain
      DHA levels.

PMID- 29582414
TI  - The novel MU-opioid receptor agonist PZM21 depresses respiration and induces
      tolerance to antinociception.
AB  - BACKGROUND AND PURPOSE: PZM21 is a novel MU-opioid receptor ligand that has been
      reported to induce minimal arrestin recruitment and be devoid of the respiratory
      depressant effects characteristic of classical MU receptor ligands such as
      morphine. We have re-examined the signalling profile of PZM21 and its ability to
      depress respiration. EXPERIMENTAL APPROACH: G protein (Gi ) activation and
      arrestin-3 translocation were measured in vitro, using BRET assays, in HEK 293
      cells expressing MU receptors. Respiration (rate and tidal volume) was measured
      in awake, freely moving mice by whole-body plethysmography, and antinociception
      was measured by the hot plate test. KEY RESULTS: PZM21 (10-9 - 3 * 10-5  M)
      produced concentration-dependent Gi activation and arrestin-3 translocation.
      Comparison with responses evoked by morphine and DAMGO revealed that PZM21 was a
      low efficacy agonist in both signalling assays. PZM21 (10-80 mg.kg-1 ) depressed
      respiration in a dose-dependent manner. The respiratory depression was due to a
      decrease in the rate of breathing not a decrease in tidal volume. On repeated
      daily administration of PZM21 (twice daily doses of 40 mg.kg-1 ), complete
      tolerance developed to the antinociceptive effect of PZM21 over 3 days but no
      tolerance developed to its respiratory depressant effect. CONCLUSION AND
      IMPLICATIONS: These data demonstrate that PZM21 is a low efficacy MU receptor
      agonist for both G protein and arrestin signalling. Contrary to a previous
      report, PZM21 depresses respiration in a manner similar to morphine, the
      classical opioid receptor agonist.

PMID- 29582415
TI  - Tricks of the trade: delivering reliable healthcare.

PMID- 29582416
TI  - Body fat reduction without cardiovascular changes in mice after oral treatment
      with the MAO inhibitor phenelzine.
AB  - BACKGROUND AND PURPOSE: Phenelzine is an antidepressant drug known to increase
      the risk of hypertensive crisis when dietary tyramine is not restricted. However,
      this MAO inhibitor inhibits other enzymes not limited to the nervous system. Here
      we investigated if its antiadipogenic and antilipogenic effects in cultured
      adipocytes could contribute to decreased body fat in vivo, without unwanted
      hypertensive or cardiovascular effects. EXPERIMENTAL APPROACH: Mice were fed a
      standard chow and given 0.028% phenelzine in drinking water for 12 weeks. Body
      composition was determined by NMR. Cardiovascular dysfunction was assessed by
      heart rate variability analyses and by evaluation of cardiac oxidative stress
      markers. MAO activity, hydrogen peroxide release and triacylglycerol turnover
      were assayed in white adipose tissue (WAT), alongside determination of glucose
      and lipid circulating levels. KEY RESULTS: Phenelzine-treated mice exhibited
      lower body fat content, subcutaneous WAT mass and lipid content in skeletal
      muscles than control, without decreased body weight gain or food consumption. A
      modest alteration of cardiac sympathovagal balance occurred without depressed
      aconitase activity. In WAT, phenelzine impaired the lipogenic but not the
      antilipolytic actions of insulin, MAO activity and hydrogen peroxide release.
      Phenelzine treatment lowered non-fasting blood glucose and phosphoenolpyruvate
      carboxykinase expression. In vitro, high doses of phenelzine decreased both
      lipolytic and lipogenic responses in mouse adipocytes. CONCLUSION AND
      IMPLICATIONS: As phenelzine reduced body fat content without affecting
      cardiovascular function in mice, it may be of benefit in the treatment of obesity
      associated complications, with the precautions of use recommended for
      antidepressant therapy.

PMID- 29582418
TI  - Management of uterine ectopic pregnancy - local vs. systemic methotrexate.
AB  - INTRODUCTION: The aim of this study was to compare ultrasound-guided local
      methotrexate (MTX) vs. systemic methotrexate in uterine ectopic pregnancy
      regarding the beta human chorionic gonadotropin (hCG) clearance duration.
      MATERIAL AND METHODS: Patients with interstitial pregnancy, cervical pregnancy or
      cesarean scar pregnancy were included. Methotrexate was administered locally
      ultrasound-guided (25 mg methotrexate fixed dose) or systemically (intramuscular;
      50 mg/m2 body weight). Beta hCG clearance duration in days formed the main
      outcome measure. RESULTS: Forty-six patients with uterine ectopic pregnancy were
      included. The mean estimated beta hCG clearance duration was 29.2 days longer in
      patients with local methotrexate compared with systemic methotrexate (64.7 vs.
      31.5 days, respectively; p = 0.026). There was no significant difference between
      local vs. systemic methotrexate regarding adverse events such as bleeding (p =
      0.376), pain (p = 0.146) or secondary surgery (p = 0.631). There was no
      association of initial beta hCG levels (p = 0.746), initial progesterone levels
      (p = 0.870) or patients' age (p = 0.604) and the beta hCG clearance duration. No
      significant difference in beta hCG clearance duration comparing local
      methotrexate injection with aspiration vs. local methotrexate injection without
      aspiration could be found (mean 49.4 and 71.6 days, respectively, p = 0.225).
      CONCLUSIONS: In patients with uterine ectopic pregnancies, the mean estimated
      beta hCG clearance duration was 29.2 days longer when applying local methotrexate
      compared with systemic methotrexate.

PMID- 29582417
TI  - Analysis of the distribution of spinal NOP receptors in a chronic pain model
      using NOP-eGFP knock-in mice.
AB  - BACKGROUND AND PURPOSE: The nociceptin/orphanin FQ opioid peptide (NOP) receptor
      system plays a significant role in the regulation of pain. This system functions
      differently in the spinal cord and brain. The mechanism by which the NOP receptor
      agonists regulate pain transmission in these regions is not clearly understood.
      Here, we investigate the peripheral and spinal NOP receptor distribution and
      antinociceptive effects of intrathecal nociceptin/orphanin FQ (N/OFQ) in chronic
      neuropathic pain. EXPERIMENTAL APPROACH: We used immunohistochemistry to
      determine changes in NOP receptor distribution triggered by spinal nerve ligation
      (SNL) using NOP-eGFP knock-in mice. Antinociceptive effects of intrathecal N/OFQ
      on SNL-mediated allodynia and heat/cold hyperalgesia were assessed in wild-type
      mice. KEY RESULTS: NOP-eGFP immunoreactivity was decreased by SNL in the spinal
      laminae I and II outer, regions that mediate noxious heat stimuli. In contrast,
      immunoreactivity of NOP-eGFP was unchanged in the ventral border of lamina II
      inner, which is an important region for the development of allodynia. NOP-eGFP
      expression was also decreased in a large number of primary afferents in the L4
      dorsal root ganglion (DRG) of SNL mice. However, SNL mice showed increased
      sensitivity, compared to sham animals to the effects of i.t administered N/OFQ
      with respect to mechanical as well as thermal stimuli. CONCLUSIONS AND
      IMPLICATIONS: Our findings suggest that the spinal NOP receptor system attenuates
      injury-induced hyperalgesia by direct inhibition of the projection neurons in the
      spinal cord that send nociceptive signals to the brain and not by inhibiting
      presynaptic terminals of DRG neurons in the superficial lamina.

PMID- 29582419
TI  - Synthesis and biological evaluation of novel cyclopropyl derivatives as subtype
      selective ligands for estrogen receptor.
AB  - OBJECTIVES: Tamoxifen is the most commonly used selective estrogen receptor
      modulators (SERMs); however, patients often develop the acquired drug resistance
      on tamoxifen therapy. The aim of this study was to develop new SERMs. METHODS:
      Several novel cyclopropyl derivatives were designed and synthesized. The binding
      affinities of these compounds as well as the selectivity on subtype of estrogen
      receptor (ER) were assessed by fluorescence polarization. The antagonistic
      activity was also evaluated by dual-luciferase reporter assay. KEY FINDINGS: Our
      data identified five compounds (9a, 9b, 9d, 9e and 9f) with a higher selectivity
      on ERalpha than ERbeta subtype, warranting further development as a subtype
      selective ER modulator. The study of antiestrogen activity also demonstrated that
      compounds 9a, 9c-f acted as full functional antagonists for ERalpha. These
      compounds had no or very low cytotoxicity. CONCLUSIONS: Although these
      cyclopropyl derivatives showed lower binding affinities on ERs compared to 17beta
      estradiol, five of these compounds exhibited binding to ERalpha only and
      therefore might serve as a promising lead compound for further development of
      novel subtype-selective SERMs.

PMID- 29582420
TI  - Redescription of Dekeyseria picta (Siluriformes; Loricariidae), a poorly known
      ancistrin from the Amazon and Orinoco Basins.
AB  - A re-evaluation of Dekeyseria brachyura and D. pulchra found them to be junior
      synonyms of D. picta, the oldest species among these congeners, based on
      continuous intraspecific variation in morphometrics and colour pattern.
      Examination of material deposited at Brazilian and Venezuelan collections,
      including the original type specimens of Ancistrus brachyurus and A. pictus, plus
      samples recently collected in the Rio Negro, Amazonas, Brazil, allowed re
      evaluation of the taxonomic status of D. picta and provides additional
      information on its distribution, habitats and reproductive strategies.

PMID- 29582421
TI  - The enhanced recovery after surgery (ERAS) Greenie Board: a Navy-inspired quality
      improvement tool.
AB  - The United States Navy uses a visual feedback system for pilots, named 'the
      Greenie Board', to improve flight manoeuvres on aircraft carriers. Given that
      increased compliance with enhanced recovery after surgery protocols reduces
      postoperative complications, we decided to apply a similar feedback system to our
      institutional enhanced recovery programme. We undertook a prospective 12-month
      audit of 194 patients assigned to our enhanced recovery programme and evaluated
      adherence to the anaesthesia-related components of our protocol, before and after
      implementing a Greenie Board. A compliance score was calculated by summing points
      for adherence to: intra-operative antibiotic prophylaxis; temperature management;
      goal-directed intravenous fluid therapy; postoperative nausea and vomiting
      prophylaxis; and postoperative fluid restriction. The score for each patient was
      then colour-coded and anonymously displayed for each anaesthetist on a Greenie
      Board within the operating theatre suite. Protocol adherence improved
      significantly following introduction, with 'Green' scores (acceptable compliance)
      increasing from 33% to 72% of patients (p < 0.0001). The greatest improvement was
      seen with anti-emetic prophylaxis (49% to 70%, p = 0.004) with a consequent
      reduction in postoperative nausea and vomiting (OR 0.42, 95% CI 0.19-0.88, p =
      0.021). We did not observe a decrease in other postoperative complications nor
      hospital length of stay. We conclude that this US Navy-inspired feedback system
      is an easily implemented, low-cost quality improvement tool that significantly
      improved adherence to intra-operative components of our enhanced recovery
      protocol. The system lends itself to global scaling to drive quality improvement
      in healthcare delivery and would be suited to institutions without electronic
      medical records, including low-resource countries.

PMID- 29582422
TI  - The effect of spinal hyperbaric bupivacaine-fentanyl or hyperbaric bupivacaine on
      uterine tone and fetal heart rate in labouring women: a randomised controlled
      study.
AB  - The mechanism for fetal heart rate abnormalities following spinal opioids remains
      controversial. We evaluated uterine tone, using an intra-uterine pressure
      catheter, and fetal heart rate abnormalities in 30 women in spontaneous labour
      with cervical dilation of 3-5 cm having combined spinal-epidural analgesia. Women
      were randomly assigned to receive a spinal with 2.0 mg hyperbaric bupivacaine
      plus 15 MUg fentanyl, or 2.5 mg hyperbaric bupivacaine. The primary outcome
      measure was an increase > 10 mmHg in baseline uterine tone in the 30-min period
      following spinal injection. Only three (20%) women who had a bupivacaine-fentanyl
      spinal showed a > 10 mmHg increase in baseline tone vs. none who had bupivacaine
      (p = 0.63). The mean (SD) baseline uterine tone after the spinal injection was
      13.3 (7.0) mmHg in the bupivacaine-fentanyl group and 7.7 (2.5) mmHg in the
      bupivacaine group (p = 0.01). Seven (47%) in the bupivacaine-fentanyl group
      showed new onset fetal heart rate changes during the 30-min period after the
      spinal, compared with two (13%) in the bupivacaine group (p = 0.04); however,
      these were transient and responded to intra-uterine resuscitation. Pain scores,
      sensory and motor block as well as neonatal outcomes were comparable between the
      groups. We found that raised baseline uterine tone was not more frequent when
      using bupivacaine-fentanyl rather than bupivacaine in the spinal component of
      combined spinal-epidural, although absolute values of baseline tone were higher,
      and fetal heart rate changes more frequent, in the former group.

PMID- 29582423
TI  - A PRDX1-p38alpha heterodimer amplifies MET-driven invasion of IDH-wildtype and
      IDH-mutant gliomas.
AB  - The Peroxiredoxin 1 (PRDX1) gene maps to chromosome arm 1p and is hemizygously
      deleted and epigenetically silenced in isocitrate dehydrogenase 1 or 2 (IDH)
      mutant and 1p/19q-codeleted oligodendroglial tumors. In contrast, IDH-wildtype
      astrocytic gliomas including glioblastomas mostly lack epigenetic silencing and
      express PRDX1 protein. In our study, we investigated how PRDX1 contributes to the
      infiltrative growth of IDH-wildtype gliomas. Focusing on p38alpha-dependent
      pathways, we analyzed clinical data from 133 patients of the NOA-04 trial cohort
      to look for differences in the gene expression profiles of gliomas with wildtype
      or mutant IDH. Biochemical interaction studies as well as in vitro and ex vivo
      migration studies were used to establish a biological role of PRDX1 in
      maintaining pathway activity. Whole-brain high-resolution ultramicroscopy and
      survival analyses of pre-clinical mouse models for IDH-wildtype gliomas were then
      used for in vivo confirmation. Based on clinical data, we found that the absence
      of PRDX1 is associated with changes in the expression of MET/HGF signaling
      components. PRDX1 forms a heterodimer with p38alpha mitogen-activated protein
      kinase 14 (MAPK14), stabilizing phospho-p38alpha in glioma cells. This process
      amplifies hepatocyte growth factor (HGF)-mediated signaling and stimulates actin
      cytoskeleton dynamics that promote glioma cell migration. Whole-brain high
      resolution ultramicroscopy confirms these findings, indicating that PRDX1
      promotes glioma brain invasion in vivo. Finally, reduced expression of PRDX1
      increased survival in mouse glioma models. Thus, our preclinical findings suggest
      that PRDX1 expression levels may serve as a molecular marker for patients who
      could benefit from targeted inhibition of MET/HGF signaling.

PMID- 29582424
TI  - Antinociceptive and anti-inflammatory effects of 1,2-bis-(4 methoxyphenylselanyl)
      styrene in mice: involvement of the serotonergic system.
AB  - BACKGROUND: Pain is one of the most prevalent, costly and disabling conditions
      that reduces quality of life. Although there are many analgesics available, there
      is some concern regarding their efficacy, safety and side effects. Organic
      selenium compounds are attractive targets of various research groups due to their
      pharmacological properties. OBJECTIVES: The aim of this study was to evaluate the
      antinociceptive and anti-inflammatory activity of 1,2-bis-(4
      methoxyphenylselanyl) styrene (BMOSE) in mice, as well as to investigate the
      mechanism involved in the antinociceptive effect. METHODS: The animals were
      submitted to the formalin and glutamate tests. The assessment of the possible
      involvement of the serotonergic system in BMOSE antinociceptive activity was
      performed using the glutamate test. Also, we investigated the possible toxicity
      of the compound. KEY FINDINGS: 1,2-bis-(4-methoxyphenylselanyl) styrene (0.1-50
      mg/kg, i.g.) was efficient in avoiding nociception induced by glutamate and
      formalin and also reduced paw oedema. The possible involvement of 5-HT3
      serotoninergic receptor antagonist ondansetron blocked the antinociceptive effect
      of BMOSE. The acute toxicity assays did not show any toxicity related to the
      administration of BMOSE (200 mg/kg). CONCLUSIONS: It is possible to conclude that
      BMOSE has both antinociceptive and anti-inflammatory activity, and the
      serotoninergic system, more specifically, the 5-HT3 receptor, is involved in the
      effect.

PMID- 29582425
TI  - Good social skills despite poor theory of mind: exploring compensation in autism
      spectrum disorder.
AB  - BACKGROUND: It is proposed that some individuals with Autism Spectrum Disorder
      (ASD) can 'compensate' for their underlying difficulties (e.g. in theory of mind;
      ToM), thus demonstrating relatively few behavioural symptoms, despite continued
      core cognitive deficits. The mechanisms underpinning compensation are largely
      unexplored, as is its potential impact on mental health. This study aimed to
      estimate compensation patterns in ASD, by contrasting overt social behaviour with
      ToM task performance, in order to compare the characteristics of 'Low' and 'High'
      Compensators. METHODS: A total of 136 autistic adolescents, from the ongoing
      Social Relationships Study, completed a range of cognitive tasks, the Autistic
      Diagnostic Observation Schedule (ADOS) and a self-report anxiety questionnaire.
      Participants were assigned compensation group status; High Compensators
      demonstrated good ADOS scores despite poor ToM performance, while Low
      Compensators demonstrated similarly poor ToM, accompanied by poor ADOS scores.
      RESULTS: High Compensators demonstrated better IQ and executive function (EF),
      but greater self-reported anxiety, compared with Low Compensators. Such
      differences were not found when comparing individuals who had good versus poor
      ADOS scores, when ToM performance was good. Other core autistic characteristics
      (weak central coherence, nonsocial symptoms) did not differentiate the High and
      Low Compensators. CONCLUSIONS: IQ, EF and anxiety appear to be implicated in the
      processes by which certain autistic young people can compensate for their
      underlying ToM difficulties. This tendency to compensate does not appear to
      reflect the severity of 'hit' for ASD per se, suggesting that well-compensated
      individuals are not experiencing a milder form of ASD. The construct of
      compensation in ASD has implications for research and clinical practice.

PMID- 29582426
TI  - Prevalence of BRCA1/2 large genomic rearrangements in Chinese women with sporadic
      triple-negative or familial breast cancer.
AB  - The prevalence of BRCA1/2 large genomic rearrangements (LGRs) and their
      underlying mechanisms have not been fully evaluated in Chinese women with breast
      cancer. In this study, we determined the prevalence of BRCA1/2 LGRs in 834
      patients with familial breast cancer (FBC) and 660 patients with sporadic triple
      negative breast cancer (TNBC) who were negative for BRCA1/2 small-range mutations
      using the multiplex ligation-dependent probe amplification method. We found that
      20 index patients (2.4%) in the FBC group carried a BRCA1 or BRCA2 LGR, and the
      frequencies of BRCA1 and BRCA2 LGRs were 1.6% and 0.8%, respectively. Seven index
      patients (1.1%) carried a BRCA1 LGR in 660 sporadic TNBC patients, whereas no
      BRCA2 LGRs were found in these patients. Among the BRCA1/2 LGRs, 48.1% (13/27)
      were novel, and the breakpoints of the majority of the LGRs were identified.
      PsiBRCA1-mediated homologous recombination (HR) and Alu-mediated HR/non
      homologous end-joining (NHEJ) accounted for 40% and 30% of the BRCA1 LGRs,
      respectively. Alu-mediated HR accounted for 71.4% of the BRCA2 LGRs, and the
      remaining one-third was generated through Long interspersed nuclear elements
      (LINE)-mediated NHEJ. Our findings suggest that both FBC patients and sporadic
      TNBC patients should be tested for BRCA1/2 LGRs.

PMID- 29582427
TI  - IgE and D-dimer baseline levels are higher in responders than nonresponders to
      omalizumab in chronic spontaneous urticaria.

PMID- 29582429
TI  - Early intervention (mobilization or active exercise) for critically ill adults in
      the intensive care unit.
AB  - BACKGROUND: Survivors of critical illness often experience a multitude of
      problems that begin in the intensive care unit (ICU) or present and continue
      after discharge. These can include muscle weakness, cognitive impairments,
      psychological difficulties, reduced physical function such as in activities of
      daily living (ADLs), and decreased quality of life. Early interventions such as
      mobilizations or active exercise, or both, may diminish the impact of the
      sequelae of critical illness. OBJECTIVES: To assess the effects of early
      intervention (mobilization or active exercise), commenced in the ICU, provided to
      critically ill adults either during or after the mechanical ventilation period,
      compared with delayed exercise or usual care, on improving physical function or
      performance, muscle strength and health-related quality of life. SEARCH METHODS:
      We searched CENTRAL, MEDLINE, Embase and CINAHL. We searched conference
      proceedings, reference lists of retrieved articles, databases of trial registries
      and contacted experts in the field on 31 August 2017. We did not impose
      restrictions on language or location of publications. SELECTION CRITERIA: We
      included all randomized controlled trials (RCTs) or quasi-RCTs that compared
      early intervention (mobilization or active exercise, or both), delivered in the
      ICU, with delayed exercise or usual care delivered to critically ill adults
      either during or after the mechanical ventilation period in the ICU. DATA
      COLLECTION AND ANALYSIS: Two researchers independently screened titles and
      abstracts and assessed full-text articles against the inclusion criteria of this
      review. We resolved any disagreement through discussion with a third review
      author as required. We presented data descriptively using mean differences or
      medians, risk ratios and 95% confidence intervals. A meta-analysis was not
      possible due to the heterogeneity of the included studies. We assessed the
      quality of evidence with GRADE. MAIN RESULTS: We included four RCTs (a total of
      690 participants), in this review. Participants were adults who were mechanically
      ventilated in a general, medical or surgical ICU, with mean or median age in the
      studies ranging from 56 to 62 years. Admitting diagnoses in three of the four
      studies were indicative of critical illness, while participants in the fourth
      study had undergone cardiac surgery. Three studies included range-of-motion
      exercises, bed mobility activities, transfers and ambulation. The fourth study
      involved only upper limb exercises. Included studies were at high risk of
      performance bias, as they were not blinded to participants and personnel, and two
      of four did not blind outcome assessors. Three of four studies reported only on
      those participants who completed the study, with high rates of dropout. The
      description of intervention type, dose, intensity and frequency in the standard
      care control group was poor in two of four studies.Three studies (a total of 454
      participants) reported at least one measure of physical function. One study (104
      participants) reported low-quality evidence of beneficial effects in the
      intervention group on return to independent functional status at hospital
      discharge (59% versus 35%, risk ratio (RR) 1.71, 95% confidence interval (CI)
      1.11 to 2.64); the absolute effect is that 246 more people (95% CI 38 to 567) per
      1000 would attain independent functional status when provided with early
      mobilization. The effects on physical functioning are uncertain for a range
      measures: Barthel Index scores (early mobilization: median 75 control: versus 55,
      low quality evidence), number of ADLs achieved at ICU (median of 3 versus 0, low
      quality evidence) or at hospital discharge (median of 6 versus 4, low quality
      evidence). The effects of early mobilization on physical function measured at ICU
      discharge are uncertain, as measured by the Acute Care Index of Function (ACIF)
      (early mobilization mean: 61.1 versus control: 55, mean difference (MD) 6.10, 95%
      CI -11.85 to 24.05, low quality evidence) and the Physical Function ICU Test
      (PFIT) score (5.6 versus 5.4, MD 0.20, 95% CI -0.98 to 1.38, low quality
      evidence). There is low quality evidence that early mobilization may have little
      or no effect on physical function measured by the Short Physical Performance
      Battery score at ICU discharge from one study of 184 participants (mean 1.6 in
      the intervention group versus 1.9 in usual care, MD -0.30, 95% CI -1.10 to 0.50),
      or at hospital discharge (MD 0, 95% CI -1.00 to 0.90). The fourth study, which
      examined postoperative cardiac surgery patients did not measure physical function
      as an outcome.Adverse effects were reported across the four studies but we could
      not combine the data. Our certainty in the risk of adverse events with either
      mobilization strategy is low due to the low rate of events. One study reported
      that in the intervention group one out of 49 participants (2%) experienced oxygen
      desaturation less than 80% and one of 49 (2%) had accidental dislodgement of the
      radial catheter. This study also found cessation of therapy due to participant
      instability occurred in 19 of 498 (4%) of the intervention sessions. In another
      study five of 101 (5%) participants in the intervention group and five of 109
      (4.6%) participants in the control group had postoperative pulmonary
      complications deemed to be unrelated to intervention. A third study found one of
      150 participants in the intervention group had an episode of asymptomatic
      bradycardia, but completed the exercise session. The fourth study reported no
      adverse events. AUTHORS' CONCLUSIONS: There is insufficient evidence on the
      effect of early mobilization of critically ill people in the ICU on physical
      function or performance, adverse events, muscle strength and health-related
      quality of life at this time. The four studies awaiting classification, and the
      three ongoing studies may alter the conclusions of the review once these results
      are available. We assessed that there is currently low-quality evidence for the
      effect of early mobilization of critically ill adults in the ICU due to small
      sample sizes, lack of blinding of participants and personnel, variation in the
      interventions and outcomes used to measure their effect and inadequate
      descriptions of the interventions delivered as usual care in the studies included
      in this Cochrane Review.

PMID- 29582428
TI  - Selective late sodium current inhibitor GS-458967 suppresses Torsades de Pointes
      by mostly affecting perpetuation but not initiation of the arrhythmia.
AB  - BACKGROUND AND PURPOSE: Enhanced late sodium current (late INa ) in heart failure
      and long QT syndrome type 3 is proarrhythmic. This study investigated the
      antiarrhythmic effect and mode of action of the selective and potent late INa
      inhibitor GS-458967 (GS967) against Torsades de Pointes arrhythmias (TdP) in the
      chronic atrioventricular block (CAVB) dog. EXPERIMENTAL APPROACH:
      Electrophysiological and antiarrhythmic effects of GS967 were evaluated in
      isolated canine ventricular cardiomyocytes and CAVB dogs with dofetilide-induced
      early afterdepolarizations (EADs) and TdP, respectively. Mapping of intramural
      cardiac electrical activity in vivo was conducted to study effects of GS967 on
      spatial dispersion of repolarization. KEY RESULTS: GS967 (IC50 ~200nM)
      significantly shortened repolarization in canine ventricular cardiomyocytes and
      sinus rhythm (SR) dogs, in a concentration and dose-dependent manner. In vitro,
      despite addition of 1MUM GS967, dofetilide-induced EADs remained present in 42%
      and 35% of cardiomyocytes from SR and CAVB dogs, respectively. Nonetheless, GS967
      (787+/-265nM) completely abolished dofetilide-induced TdP in CAVB dogs (10/14
      after dofetilide to 0/14 dogs after GS967), while single ectopic beats (sEB)
      persisted in 9 animals. In vivo mapping experiments showed that GS967
      significantly reduced spatial dispersion of repolarization: cubic dispersion was
      significantly decreased from 237+/-54ms after dofetilide to 123+/-34ms after
      GS967. CONCLUSION AND IMPLICATIONS: GS967 terminated all dofetilide-induced TdP
      without completely suppressing EADs and sEB in vitro and in vivo, respectively.
      The antiarrhythmic mode of action of GS967, through the reduction of spatial
      dispersion of repolarization, seems to predominantly impede the perpetuation of
      arrhythmic events into TdP rather than their initiating trigger.

PMID- 29582430
TI  - Human periodontal ligament cells exhibit no endotoxin tolerance upon stimulation
      with Porphyromonas gingivalis lipopolysaccharide.
AB  - BACKGROUND/OBJECTIVES: Endotoxin tolerance is characterized by a state of
      hyporesponsiveness after confrontation with endotoxins such as
      lipopolysaccharides (LPS) at low concentrations. The aim of this study was to
      investigate, whether pretreatment with Porphyromonas gingivalis leads to
      endotoxin tolerance induction and possible alterations in toll-like receptor
      (TLR) 2- and 4-induced response in human periodontal ligament cells (hPDLCs).
      MATERIAL AND METHODS: Primary hPDLCs were pretreated with P. gingivalis (0.1 or
      0.3 MUg/mL) LPS for 24 hours and afterwards treated with one of the following
      stimuli: P. gingivalis LPS (1 MUg/mL); TLR4 agonist Escherichia coli LPS (0.1
      MUg/mL; 1 MUg/mL); TLR2 agonist Pam3CSK4 (0.1 MUg/mL; 1 MUg/mL). The protein
      expression of interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 was
      analyzed with quantitative polymerase chain reaction and enzyme-linked
      immunosorbent assay. Gene expression levels of TLR2 and TLR4 were determined by
      quantitative polymerase chain reaction. RESULTS: Pretreatment of cells with low
      concentrations of P. gingivalis LPS did not result in lower production of IL-6,
      IL-8 and monocyte chemotactic protein-1 compared to control group. In some cases,
      pretreated cells exhibited lower gene expression levels of TLR2 and TLR4 compared
      to non-pretreated cells. CONCLUSION: The results of this study implicate that
      hPDLCs do not develop endotoxin tolerance. Furthermore, the amplitude of the
      inflammatory response shows no significant dependency on TLR2 and TLR4 expression
      levels.

PMID- 29582431
TI  - Retinal histogenesis in an altricial avian species, the zebra finch (Taeniopygia
      guttata, Vieillot 1817).
AB  - Comparative developmental studies have shown that the retina of altricial fish
      and mammals is incompletely developed at birth, and that, during the first days
      of life, maturation proceeds rapidly. In contrast, precocial fish and mammals are
      born with fully differentiated retinas. Concerning birds, knowledge about retinal
      development is generally restricted to a single order of precocial birds,
      Galliformes, due to the fact that both the chicken and the Japanese quail are
      considered model systems. However, comparison of embryonic pre-hatchling retinal
      development between altricial and precocial birds has been poorly explored. The
      purpose of this study was to examine the morphogenesis and histogenesis of the
      retina in the altricial zebra finch (Taeniopygia guttata, Vieillot 1817) and
      compare the results with those from previous studies in the precocial chicken.
      Several maturational features (morphogenesis of the optic vesicle and optic cup,
      appearance of the first differentiated neurons, the period in which the non
      apical cell divisions are observable, and the emergence of the plexiform layers)
      were found to occur at later stages in the zebra finch than in the chicken. At
      hatching, the retina of T. guttata showed the typical cytoarchitecture of the
      mature tissue, although features of immaturity were still observable, such as a
      ganglion cell layer containing many thick cells, very thin plexiform layers, and
      poorly developed photoreceptors. Moreover, abundant mitotic activity was detected
      in the entire retina, even in the regions where the layering was complete. The
      circumferential marginal zone was very prominent and showed abundant mitotic
      activity. The partially undifferentiated stage of maturation at hatching makes
      the T. guttata retina an appropriate model with which to study avian postnatal
      retinal neurogenesis.

PMID- 29582432
TI  - Smoking, alcohol and cancer mortality in Eastern European men: Findings from the
      PrivMort retrospective cohort study.
AB  - Eastern European men have among the highest cancer mortality rates globally.
      Prevalence of smoking and alcohol intake in this region is also high. The aim of
      our study was to calculate population attributable risk fraction (PARF) of cancer
      deaths from smoking and alcohol in Russia, Belarus and Hungary, and to examine
      the contribution of these lifestyle factors to differences in male cancer
      mortality in the three countries. Data were collected as part of the PrivMort
      retrospective cohort study. Randomly selected participants living in mid-size
      towns in Russia, Belarus and Hungary provided information on smoking habits,
      alcohol consumption, vital status and cause of death (if applicable) of male
      relatives (fathers, siblings and partners). PARF of cancer deaths (age 35-79) due
      to smoking, alcohol consumption and both combined was estimated between 2001 and
      2013. Among 72,190 men, 4,702 died of cancer. Age standardized cancer mortality
      rates were similar to official data in all three countries. The estimated PARF
      (95% CI) associated with measures of smoking, alcohol consumption, both combined,
      and overall smoking or drinking were 25% (19-30), 2% (0-4), 29% (19-39), 43% (32
      53) in Russia, 18% (8-28), 2% (-1 to 6), 28% (20-35), 38% (25-50) in Belarus and
      17% (13-20), 1% (0-3), 25% (20-30), 35% (28-42) in Hungary, respectively. These
      results suggest that in Eastern Europe, at least one third of cancer deaths in
      males may have been attributable to smoking and/or alcohol consumption in recent
      years. Health policies targeting these lifestyle factors can have a major impact
      on population health.

PMID- 29582433
TI  - Calcaneal adduction and eversion are coupled to talus and tibial rotation.
AB  - The purpose of this study was to quantify isolated coupling mechanisms of
      calcaneal adduction/abduction and calcaneal eversion/inversion to proximal bones
      in vitro. The in vitro approach is necessary because in vivo both movements
      appear together, making it impossible to determine the extent of their individual
      contribution to overall ankle joint coupling. Eight fresh frozen foot-leg
      specimens were tested. Data describing bone orientation and coupling mechanisms
      between segments were obtained using bone pin marker triads. The bone movement
      was described in a global coordinate system to examine the coupling between the
      calcaneus, talus and tibia. The strength of coupling was determined by means of
      the slope of a linear least squares fit to an angle-angle plot. The coupling
      coefficients in the present study indicate that not only calcaneal
      eversion/inversion (coupling coefficient: 0.68 +/- 0.15) but to an even greater
      extent calcaneal adduction/abduction (coupling coefficient: 0.99 +/- 0.10) was
      transferred into talus and tibial rotation, highlighting the relevance of
      calcaneal adduction for the overall ankle joint coupling. The results of this
      study present the possibility that controlling calcaneal adduction/abduction can
      affect talus and tibial rotation and therefore the possible genesis of overuse
      knee injuries.

PMID- 29582434
TI  - Latent class analysis of indicators of intolerance of uncertainty.
AB  - Intolerance of Uncertainty (IU) is a transdiagnostic vulnerability factor
      involved in depression and anxiety symptoms and disorders. IU encompasses
      Prospective IU ("Unforeseen events upset me greatly") and Inhibitory IU ("The
      smallest doubt can stop me from acting"). Research has yet to explore whether
      subgroups or classes of people exist characterized by different profiles of IU.
      This study used latent class analysis to identify such subgroups and examined if
      different classes of IU were distinct in terms of several cognitive
      vulnerabilities and psychological symptoms. Data were obtained from 519 students
      completing a 12-item measure of IU. Four subgroups were identified, characterized
      by low IU, predominantly Prospective IU, predominantly Inhibitory IU, and high
      IU, respectively. People in the high IU class reported cognitive vulnerabilities
      and depression and anxiety more than people in the low IU class. Inhibitory IU
      was more strongly associated with poor outcomes than was Prospective IU.

PMID- 29582435
TI  - Combining long-acting bronchodilators with different mechanisms of action: A
      pharmacological approach to optimize bronchodilation of equine airways.
AB  - The ultra long-acting beta2 -adrenoceptor agonist olodaterol plus the ultra long
      acting muscarinic antagonist tiotropium bromide are known to relax equine
      airways. In human bronchi combining these drugs elicits a positive interaction,
      thus we aimed to characterize this information further in equine isolated airways
      stimulated by electrical field stimulation (EFS) and using the Concentration
      Reduction Index (CRI) and Combination Index (CI) equations. The drugs were
      administered alone and together by reproducing ex vivo the concentration-ratio
      delivered by the currently available fixed-dose combination (1:1). The single
      agents elicited a significant (p < .05) concentration-dependent reduction in the
      EFS-induced contractility, that was synergistically improved (CI 0.18) when
      administered in combination (0.9 logarithms more potent, 24% more effective than
      the monocomponents). The drugs mixture allowed a reduction in the concentration
      of olodaterol from ?1 to ?2.3 logarithms. A favorable CRI was detected also for
      tiotropium bromide, whose concentration can be reduced ?1 logarithm at medium
      effect levels, remaining positive up to submaximal relaxant effect in the
      presence of olodaterol. The combination of tiotropium bromide/olodaterol allows
      the reduction in the concentration of the monocomponents to achieve airway smooth
      muscle relaxation, thus potentially decreases the risk of adverse events when
      these drugs are used to treat severe asthmatic horses.

PMID- 29582436
TI  - Modifiers of mesenchymal stem cell quantity and quality.
AB  - BACKGROUND: Clinical trials involving mesenchymal stem cell (MSC) therapy have
      variable outcomes. We hypothesize this is largely attributed to donor-to-donor
      variability and tissue of origin. STUDY DESIGN AND METHODS: We examined
      proliferation rates, cytokine secretion profiles, and differentiation capability
      of seven bone marrow-derived MSCs (BM-MSCs) and 16 adipose tissue-derived MSCs
      (AD-MSCs) from 23 donors. RESULTS: AD-MSCs had the capacity to undergo more than
      40 population doublings, while the BM-MSC proliferation rate was found to be
      considerably slower. We observed more donor-to-donor variability in proliferation
      rates of BM-MSCs than with AD-MSCs. Cytokine analysis revealed that secretion of
      eight cytokines was significantly increased by AD-MSCs at Passage (P)3 compared
      with P1, while for BM-MSCs at P3 relative to P1, only interleukin-8 and RANTES
      secretion was significantly increased. By P5, secretion of all cytokines by AD
      MSCs was either decreased or unchanged relative to P1. In contrast, cytokine
      secretion by BM-MSCs at P5 was mostly unchanged, although secretion of six
      cytokines was significantly increased relative to P1. When we compared cytokine
      secretion between AD-MSCs and BM-MSCs at P3, AD-MSCs significantly secreted
      higher concentrations of cytokines than BM-MSCs while the opposite was observed
      at P5. This suggests that BM-MSCs are relatively more potent at P5 while AD-MSCs
      are relatively more potent at P3. AD-MSCs and BM-MSCs exhibited the capacity for
      chondrogenic differentiation. AD-MSCs and BM-MSCs appeared to display a more
      enhanced inclination toward adipogenic and osteogenic differentiation,
      respectively. CONCLUSION: MSC physiology is significantly influenced by donor
      variability and tissue of origin and this should be considered when designing
      clinical trials.

PMID- 29582437
TI  - Red blood cell transfusion after a global strategy for early detection and
      treatment of iron deficiency anemia: three-year results of a prospective
      observational study.
AB  - BACKGROUND: Anemia is the main indication for red blood cell (RBC) transfusion
      and iron deficiency is the most prevalent, preventable, and treatable cause of
      anemia worldwide. We aimed to assess the impact of iron deficiency anemia (IDA)
      on RBC transfusion by means of a program for prevention, early detection, and
      treatment. STUDY DESIGN AND METHODS: A prospective observational study was
      conducted starting in 2014 after an intervention in clinical practice in Melilla,
      a peripheral city isolated by 207 km sea distance to nearest continental Spain.
      Recommendations were proposed for first-step diagnosis of iron deficiency in the
      laboratory, oral iron prevention and treatment in primary care, and intravenous
      iron complexes and RBC transfusion for hospital management. Reduction in RBC use
      for years 2014 to 2016 was the primary outcome, with the period 2010 to 2013
      considered as baseline performance for statistical analysis. RESULTS: Compared to
      baseline, there was a significant (p < 0.05) increase in mean (+/-SD) yearly
      reference population (79,748 +/- 3265 vs. 85,376 +/- 781), ferritin assays (6980
      +/- 997 vs. 11,794 +/- 1567), admissions (6768 +/- 239 vs. 7629 +/- 191), and
      subjects exposed to iron therapy (3975 +/- 0.0 vs. 4667 +/- 21 for oral, 54 +/- 7
      vs. 257 +/- 109 for sucrose, and 128 +/- 9 vs.176 +/- 15 for carboxymaltose
      iron). Mean yearly number of RBC units transfused decreased (1622 +/- 112 vs.
      1434 +/- 44; p = 0.043), with a mean reduction of 11.6% from baseline, or 21.4%
      when estimated by units transfused per 1000 admissions. CONCLUSIONS: Management
      of IDA is a target to avoid RBC transfusion, and awareness of this health problem
      should be among the first pillars for any patient blood management program.

PMID- 29582438
TI  - A pilot serosurvey of Babesia microti in Chinese blood donors.
AB  - BACKGROUND AND OBJECTIVES: Babesia spp. are tick-borne, intraerythrocytic
      protozoan parasites, several of which are transfusion-transmissible. Transfusion
      transmitted babesiosis poses serious risk to a diverse patient population,
      including neonates, patients aged >50 years, the asplenic and the
      immunocompromised that are over-represented among transfusion recipients. Despite
      reports of B. microti and B. venatorum in People's Republic of China (PRC), no
      surveillance of blood donors for Babesia has previously been undertaken. We
      sought to determine the rates of B. microti seroreactivity in a sample of blood
      donors in the PRC. MATERIALS AND METHODS: A pilot serosurvey was conducted of
      community blood donors (n = 1000) who donated July-August 2016 at Mudanjiang
      Blood Center (Heilongjiang Province) using indirect fluorescent antibody testing
      for antibodies against B. microti. The slides were prepared using B. microti
      infected hamster blood. Samples that were initially positive to a titre of 64
      were subjected to repeat IFA testing. Final seroreactivity was based on repeat
      reactivity to >=64. RESULTS: A total of 1000 individual donor samples were
      evaluated, comprising 888 whole blood and 112 platelet donations. Thirteen of
      1000 (1.3%) donors were seroreactive for B. microti [8 (0.8%) and five (0.05%) at
      titres of 64 and 128, respectively]. CONCLUSION: Our preliminary findings support
      the need for expanded Babesia surveillance in Chinese blood donors, replete with
      molecular evaluation, to evaluate the risk to the blood supply.

PMID- 29582439
TI  - Radiation dose dependence on subject size in abdominal computed tomography: Water
      phantom and patient model comparison.
AB  - PURPOSE: Development of patient organ dose evaluation method in computed
      tomography (CT) needs to model the correlation between organ dose and patient
      size, under various conditions of scan length, tube current lineshape, and organ
      location. To facilitate this task, this work was to perform a comprehensive study
      of the relationship between the dose to water phantom and its diameter under
      various settings of phantom axis, scan length, and the location across or beyond
      the scanned range. METHODS: A dose calculation algorithm and the published data
      by Li et al. [Med. Phys. 39, 5347-5352 (2012); 40, 031903 (2013); 43, 5878-5888
      (2016)] were used to calculate longitudinal dose distribution DL (z) in 10- to 50
      cm diameter water phantoms undergoing constant tube current scans. The
      relationship between dose and phantom diameter was examined on three phantom axes
      (center, cross-sectional average, periphery), at seven scan lengths from 15 to 70
      cm, and at eight longitudinal locations within or beyond each scan range. The
      water phantom results were compared to those of patient models of eight previous
      studies. RESULTS: For the water phantoms matching the abdominal perimeters (36.3
      124.5 cm) of the GSF family of voxelized phantoms, the median and range of DL
      (z)(water) across scan range were consistent with those of the organ doses from
      the GSF phantom abdominal scans of a previous study. In 41 water phantoms
      (diameters 10-50 cm), DL (z)(water) at locations inside scan range decreased with
      increasing phantom diameters. Exponential regression analysis of the above trend
      yielded regression parameters approximately consistent with those of phantom or
      patient models of eight previous studies. However, the usual exponential function
      might not be optimal for modeling the dose dependence on subject size. Inside
      scan range, the log(dose) vs diameter curve was non-linear on a semilogarithmic
      graph. Outside of scan range, dose might increase with larger subject sizes,
      contradicting to the exponential attenuation law. In the CT examinations of a
      patient population, direct modeling of organ dose dependence on patient size
      would be more challenging due to varying scan lengths and changing organ
      distances to the scan range centers. CONCLUSION: An efficient approach to take
      into account the abdominal organ dose dependences on other factors is to
      calculate DL (z)(water) with the water equivalent diameter, scan length, and tube
      current lineshape from the patient examinations, and to evaluate the organ dose
      to DL (z)(water) ratio, where z is at the organ's longitudinal location. The
      ratio may be used for abdominal organ dose evaluation in the patient
      examinations. How to make use of DL (z)(water) for organ dose evaluation in other
      body regions may be explored in the future.

PMID- 29582440
TI  - A preclinical Talbot-Lau prototype for x-ray dark-field imaging of human-sized
      objects.
AB  - PURPOSE: Talbot-Lau x-ray interferometry provides information about the
      scattering and refractive properties of an object - in addition to the object's
      attenuation features. Until recently, this method was ineligible for imaging
      human-sized objects as it is challenging to adapt Talbot-Lau interferometers
      (TLIs) to the relevant x-ray energy ranges. In this work, we present a
      preclinical Talbot-Lau prototype capable of imaging human-sized objects with
      proper image quality at clinically acceptable dose levels. METHODS: The TLI is
      designed to match a setup of clinical relevance as closely as possible. The
      system provides a scan range of 120 * 30 cm2 by using a scanning beam geometry.
      Its ultimate load is 100 kg. High aspect ratios and fine grid periods of the
      gratings ensure a reasonable setup length and clinically relevant image quality.
      The system is installed in a university hospital and is, therefore, exposed to
      the external influences of a clinical environment. To demonstrate the system's
      capabilities, a full-body scan of a euthanized pig was performed. In addition,
      freshly excised porcine lungs with an extrinsically provoked pneumothorax were
      mounted into a human thorax phantom and examined with the prototype. RESULTS:
      Both examination sequences resulted in clinically relevant image quality - even
      in the case of a skin entrance air kerma of only 0.3 mGy which is in the range of
      human thoracic imaging. The presented case of a pneumothorax and a reader study
      showed that the prototype's dark-field images provide added value for pulmonary
      diagnosis. CONCLUSION: We demonstrated that a dedicated design of a Talbot-Lau
      interferometer can be applied to medical imaging by constructing a preclinical
      Talbot-Lau prototype. We experienced that the system is feasible for imaging
      human-sized objects and the phase-stepping approach is suitable for clinical
      practice. Hence, we conclude that Talbot-Lau x-ray imaging has potential for
      clinical use and enhances the diagnostic power of medical x-ray imaging.

PMID- 29582441
TI  - D-immunized blood donors who are female and who possess at least one HLA-DRB1*15
      allele show a propensity for high serum RhIG production.
AB  - BACKGROUND: D- individuals with previous D-incompatible pregnancies and/or blood
      transfusions, as well as those who are actively immunized with small-volume D+
      red blood cells (RBCs), are stimulated to produce RhIG. Many factors could
      influence the stimulation of immunoglobulin production in response to foreign
      antigen (such as antigen immunogenicity and genetic factors), and it is unknown
      whether genetic markers could potentially identify responder anti-D donors. STUDY
      DESIGN AND METHODS: Anti-D donors were assigned a responder profile based on
      their serum RhIG levels (n = 431). A subset of donors (n = 272) had DNA extracted
      for polymerase chain reaction genotyping assays for target genes in antigen
      presentation and pathogen recognition receptors (TLR2, TLR4, CD14, FcgammaRIIA,
      and the MHC Class II locus HLA-DRB1). Statistical tests for associations between
      anti-D donor responder profiles and genetic factors were performed. RESULTS: A
      large proportion of our donors (38.7%) were classified as nonresponder donors,
      despite receiving multiple D+ RBC immunizations, whereas female sex was
      significantly associated with an all-responder profile (p < 0.001). The presence
      of the DRB1*15 allele and absence of the DRB1*04 allele were more likely to be
      associated with a responder anti-D donor, although not significantly after
      Bonferroni correction. A combination of the DRB1*15 allele and female sex was
      significantly associated with an anti-D donor responder profile. CONCLUSION: This
      study has identified female sex and the HLA-DRB1*15 allele as potentially useful
      markers that could be used to screen donors before entry into D immunization
      programs.

PMID- 29582442
TI  - Relationship between fetal peak systolic velocity in Middle cerebral artery and
      umbilical blood gas values and hemoglobin levels in diabetic pregnant women.
AB  - PURPOSE: To assess the relationship between peak systolic velocity in the middle
      cerebral artery (MCA-PSV) and fetal hypoxia in diabetic pregnant women requiring
      insulin therapy. METHODS: The data of diabetic pregnant women using insulin who
      were followed in our departments were reviewed retrospectively. The relationships
      between MCA-PSV and umbilical cord pO2, pCO2, base deficit, hemoglobin, and birth
      weight were analyzed. RESULTS: A total of 120 cases were included in the final
      analysis. The median (Q1 - Q3 ) gestational age at Doppler evaluation was 37
      weeks 3 days (37-38 weeks and 2 days), and the mean +/- SD gestational age at
      delivery was 38 weeks 4 days +/- 3days. The mean +/- SD hemoglobin A1c (HbA1c)
      level was 5.7% +/- 1.0% and, median (Q1 -Q3 ) daily total insulin dose was 25 U
      (10U-48U). There was no statistically significant correlation between MCA-PSV and
      pH, PO2, PCO2, base deficit, Hb, and birth weight (Spearman correlation, r:
      .001[P = .99], r:-.011[P = .90], r:-.052 [P = .51], r: .049[P = .59], r: .049 [P
      = .59], r: .030 [P = .75], respectively). Using binary logistic regression
      analysis, no independent factor for the prediction of fetal acidosis (venous pH <
      7.23), and metabolic acidosis (base deficit >6.3 mmol/L) was detected.
      CONCLUSION: MCA-PSV is not a good indicator of fetal polycythemia or chronic
      hypoxia in fetuses of diabetic pregnant women. Fetal well-being should be
      monitored with other tools in these circumstances.

PMID- 29582443
TI  - Jealousy at work: The role of rivals' characteristics.
AB  - The present study examined rival characteristics that may evoke jealousy in the
      workplace, differences between men and women in this regard, and the relationship
      between jealousy responses and intrasexual competitiveness and social comparison
      orientation. Participants were 426 male and female employees. By means of a
      questionnaire, participants were presented with a jealousy-evoking scenario after
      which jealousy responses to 24 rival characteristics were assessed. Findings
      showed that a rival's social communal attributes evoked highest levels of
      jealousy, and that, compared to men, women reported more jealousy in response to
      a rival's physical attractiveness. Overall, as individuals had higher scores on
      intrasexual competitiveness and social comparison orientation, they also
      experienced more jealousy in response to their rival, regardless of his or her
      characteristics. These findings suggest that those characteristics that are
      highly valued in employees may backfire when employees perceive co-workers as
      rivals.

PMID- 29582444
TI  - 'You must know what you mean when you say that': the morality of knowledge claims
      about ADHD in radio phone-ins.
AB  - Drawing on a corpus of radio phone-ins, we present a discursive psychological
      analysis of how mothers carefully tailor their knowledge claims regarding their
      children with Attention Deficit Hyperactivity Disorder (ADHD). Mothers typically
      claim knowledge about their children's good intentions, but not about the 'ADHD
      ness' of their conduct. Whereas the former is seen as appropriate knowledge for a
      concerned parent, the latter is treated as a matter of expert knowledge. We show
      that as soon as problematic behaviour is treated as observable from the outside
      and describable by mothers and other lay persons, it becomes vulnerable to being
      formulated as 'normal disobedience', rather than symptomatic of a professionally
      administered, doctorable condition. We argue that it is important to be aware of
      the moralities hidden in knowledge claims, as they help sustain an unproductive
      perspective in which either the child's brain or his mother is blamed for
      behaviour perceived as problematic.

PMID- 29582445
TI  - Development of new extraction method based on liquid-liquid-liquid extraction
      followed by dispersive liquid-liquid microextraction for extraction of three
      tricyclic antidepressants in plasma samples.
AB  - In the present study, a new extraction method based on a three-phase system,
      liquid-liquid-liquid extraction, followed by dispersive liquid-liquid
      microextraction has been developed and validated for the extraction and
      preconcentration of three commonly prescribed tricyclic antidepressant drugs -
      amitriptyline, imipramine, and clomipramine - in human plasma prior to their
      analysis by gas chromatography-flame ionization detection. The three phases were
      an aqueous phase (plasma), acetonitrile and n-hexane. The extraction mechanism
      was based on the different affinities of components of the biological sample
      (lipids, fatty acids, pharmaceuticals, inorganic ions, etc.) toward each of the
      phases. This provided high selectivity toward the analytes since most
      interferences were transferred into n-hexane. In this procedure, a homogeneous
      solution of the aqueous phase (plasma) and acetonitrile (water-soluble extraction
      solvent) was broken by adding sodium sulfate (as a phase separating agent) and
      the analytes were extracted into the fine droplets of the formed acetonitrile.
      Next, acetonitrile phase was mixed with 1,2-dibromoethane (as a preconcentration
      solvent at microliter level) and then the microextraction procedure mentioned
      above was performed for further enrichment of the analytes. Under the optimum
      extraction conditions, limits of detection and lower limits of quantification for
      the analytes were obtained in the ranges of 0.001-0.003 and 0.003-0.010 MUg mL-1
      , respectively. The obtained extraction recoveries were in the range of 79-98%.
      Intra- and inter-day precisions were < 7.5%. The validated method was
      successfully applied for determination of the selected drugs in human plasma
      samples obtained from the patients who received them.

PMID- 29582446
TI  - Molecular genetic studies in a case series of isolated hypoaldosteronism due to
      biosynthesis defects or aldosterone resistance.
AB  - BACKGROUND AND AIM: Hypoaldosteronism is associated with either insufficient
      aldosterone production or aldosterone resistance (pseudohypoaldosteronism).
      Patients with aldosterone defects typically present with similar symptoms and
      findings, which include failure to thrive, vomiting, hyponatremia, hyperkalemia
      and metabolic acidosis. Accurate diagnosis of these clinical conditions therefore
      can be challenging. Molecular genetic analyses can help to greatly clarify this
      complexity. The aim of this study was to obtain an overview of the clinical and
      genetic characteristics of patients with aldosterone defects due to biosynthesis
      defects or aldosterone resistance. DESIGN AND PATIENTS: We investigated the
      clinical and molecular genetic features of 8 consecutive patients with a clinical
      picture of aldosterone defects seen in our clinics during the period of May 2015
      through October 2017. We screened CYP11B2 for aldosterone synthesis defects and
      NR3C2 and the three EnaC subunits (SCNN1A, SCNN1B and SCNN1G) for aldosterone
      resistance. RESULTS: We found 4 novel and 2 previously reported mutations in the
      genes CYP11B2, NR3C2, SCNN1A and SCNN1G in 9 affected individuals from 7
      unrelated families. CONCLUSION: Molecular genetic investigations can help
      confidently diagnose these conditions and clarify the pathogenicity of
      aldosterone defects. This study may expand the clinical and genetic correlations
      of defects in aldosterone synthesis or resistance.

PMID- 29582448
TI  - Generalized lymphatic anomaly successfully treated with long-term, low-dose
      sirolimus.
AB  - Generalized lymphatic anomaly is a rare, complex, lymphatic anomaly generally
      involving soft tissues, spleen, and bones. It can lead to focal skeletal
      fragility and pathologic effusions. A recent prospective trial of sirolimus for
      complicated vascular anomalies showed partial response in seven patients with
      generalized lymphatic anomaly treated with sirolimus with a target trough level
      of 10-15 ng/mL for 1 year (Adams et al). We describe successful treatment of
      generalized lymphatic anomaly with a lower-dose, long-term course of sirolimus.

PMID- 29582447
TI  - Sleep study-guided multidisciplinary therapy (SGMT) for patients with acute
      coronary syndrome: Trial rationale and design.
AB  - Obstructive sleep apnea (OSA) is an emerging risk marker for acute coronary
      syndrome (ACS). This randomized trial aims to determine the effects of sleep
      study-guided multidisciplinary therapy (SGMT) comprising overnight sleep study,
      continuous positive airway pressure, and behavioral therapy for OSA during the
      subacute phase of ACS. We hypothesize that SGMT will reduce (1) the plasma levels
      of N-terminal pro brain natriuretic peptide and suppression of tumorigenicity 2;
      (2) the estimated 10-year risk of cardiovascular mortality as measured by the
      European Systematic Coronary Risk Evaluation (SCORE) algorithm; and (3) the
      cardiovascular event rate during a 3-year follow-up, compared with standard
      therapy. In the SGMT trial, 180 patients presenting with ACS will be randomly
      assigned to SGMT (n = 90) and standard therapy (n = 90) groups. Both groups will
      receive guideline-mandated treatment for ACS. Those assigned to SGMT will
      additionally undergo a sleep study and, if OSA is diagnosed, attend a
      multidisciplinary OSA clinic where they will receive personalized treatment
      including continuous positive airway pressure and behavioral/lifestyle
      counseling. The primary endpoint is the plasma N-terminal pro brain natriuretic
      peptide concentration at 7-month follow-up. This report presents the baseline
      characteristics of 117 patients (SGMT group: n =54; standard therapy group: n
      =63) who had been enrolled into the study as of August 31, 2017. The results of
      this trial will help us to understand whether active OSA diagnosis and treatment
      will improve the physiologic and clinical cardiovascular outcomes of this group
      of patients.

PMID- 29582449
TI  - The hOGG1 Ser326Cys polymorphism and male subfertility in Taiwanese patients with
      varicocele.
AB  - To investigate the association between the human 8-oxoguanine DNA glycosylase 1
      (hOGG1) gene Ser326Cys polymorphism and male subfertility in Taiwanese patients
      with varicocele, we made a prospective study. Ninety young male patients with
      varicocele (group 1), 50 young male patients with subclinical varicocele (group
      2) and 30 normal young male patients without varicocele (group 3) were recruited
      in this study. The hOGG1 null homozygous genotype (Cys/Cys) and the occurrence of
      a 4,977-bp deletion in mitochondrial DNA and mitochondrial copy number in
      spermatozoa were determined by polymerase chain reaction. The 8-hydroxy-2'
      deoxyguanosine (8-OHdG) content of DNA in the spermatozoa was measured using high
      performance liquid chromatography, and total antioxidant capacity (TAC) of
      seminal plasma was detected electrochemically. The rates of male subfertility
      were 31.1% (28/90) in group 1 and 22% (11/50) in group 2. Of 39 subfertile men,
      74.4% (29/39) had the hOGG1 Cys/Cys genotype. Patients in groups 1 and 2 with
      hOGG1 Cys/Cys genotype had significantly higher 8-OHdG content in sperm DNA,
      lower mitochondrial copy number in spermatozoa and lower TAC in seminal plasma
      than those with Ser/Ser or Ser/Cys genotype. Clinicians should pay more attention
      to patients with varicocele with the hOGG1 Cys/Cys genotype.

PMID- 29582450
TI  - Tamper-resistant prescription forms for narcotics in France: Should we generalize
      them?
AB  - In France, prescription of narcotics must be written on a tamper-resistant
      prescription form with specific technical particularities. Dosage and daily dose
      of medicines shall be written out entirely in letters. These prescription forms
      are also mandatory for buprenorphine, clorazepate, clonazepam, tianeptine, buccal
      midazolam and zolpidem owing to traffic, abuse or diversion. In 2012, to assess
      the use of standard and tamper-resistant prescription forms and the acceptability
      of the generalization of the latter to all medicines, a national opinion survey
      was performed, with a postal questionnaire, within three randomized samples of
      1500 prescribers (physicians, dentists and midwives). Of the 403 participating
      prescribers (participation rate of 26.8%), 373 were physicians, 14 dentists and
      16 midwives. Tamper-resistant prescription forms were used by 76.2% of
      prescribers, but only by 5.1% in a computerized version, whereas for standard
      prescription forms, 61% used computer assisted prescription software. The main
      reason was the inability of the prescription software to print these forms or to
      respect the mandatory prescription rules for narcotics. Theft and falsification
      of prescriptions had ever occurred (working life). Most prescribers (62.5%) were
      against the generalization of tamper-resistant prescription forms. Those in
      favour were for a generalization to all medicines (65%) and not only to
      psychotropic agents. Generalization of tamper-resistant prescription forms is not
      a consensual solution to prevent medicines' diversion. Some prescribers alluded
      to the possibility of dematerialization and electronic transmission of
      prescription forms, which could avoid theft, forgery or falsification.

PMID- 29582451
TI  - Topical N-acetylcysteine in ichthyosis: Experience in 18 patients.
AB  - The treatment options for ichthyosis are limited. Successful treatment with
      topical N-acetylcysteine has been reported in a small number of patients, with
      generally good results. We report the finding of a retrospective chart review of
      18 patients treated with N-acetylcysteine. Although topical N-acetylcysteine is
      an effective therapy for some patients with ichthyosis, problems with irritation,
      objectionable odor, and compounding costs limit its use.

PMID- 29582452
TI  - Design of cancer trials based on progression-free survival with intermittent
      assessment.
AB  - Therapeutic advances in cancer mean that it is now impractical to performed phase
      III randomized trials evaluating experimental treatments on the basis of overall
      survival. As a result, the composite endpoint of progression-free survival has
      been routinely adopted in recent years as it is viewed as enabling a more timely
      and cost-effective approach to assessing the clinical benefit of novel
      interventions. This article considers design of cancer trials directed at the
      evaluation of treatment effects on progression-free survival. In particular, we
      derive sample size criteria based on an illness-death model that considers cancer
      progression and death jointly while accounting for the fact that progression is
      assessed only intermittently. An alternative approach to design is also
      considered in which the sample size is derived based on a misspecified Cox model,
      which uses the documented time of progression as the progression time rather than
      dealing with the interval censoring. Simulation studies show the validity of the
      proposed methods.

PMID- 29582453
TI  - Bayesian modelling of lung function data from multiple-breath washout tests.
AB  - Paediatric respiratory researchers have widely adopted the multiple-breath
      washout (MBW) test because it allows assessment of lung function in unsedated
      infants and is well suited to longitudinal studies of lung development and
      disease. However, a substantial proportion of MBW tests in infants fail current
      acceptability criteria. We hypothesised that a model-based approach to analysing
      the data, in place of traditional simple empirical summaries, would enable more
      efficient use of these tests. We therefore developed a novel statistical model
      for infant MBW data and applied it to 1197 tests from 432 individuals from a
      large birth cohort study. We focus on Bayesian estimation of the lung clearance
      index, the most commonly used summary of lung function from MBW tests. Our
      results show that the model provides an excellent fit to the data and shed
      further light on statistical properties of the standard empirical approach.
      Furthermore, the modelling approach enables the lung clearance index to be
      estimated by using tests with different degrees of completeness, something not
      possible with the standard approach. Our model therefore allows previously unused
      data to be used rather than discarded, as well as routine use of shorter tests
      without significant loss of precision. Beyond our specific application, our work
      illustrates a number of important aspects of Bayesian modelling in practice, such
      as the importance of hierarchical specifications to account for repeated
      measurements and the value of model checking via posterior predictive
      distributions.

PMID- 29582454
TI  - Fine structure of the canal neuromasts of the lateral line system in the adult
      zebrafish.
AB  - The mechanosensory lateral line system of fish is responsible for several
      functions such as balance, hearing, and orientation in water flow and is formed
      by neuromast receptor organs distributed on head, trunk and tail. Superficial and
      canal neuromasts can be distinguished for localization and morphological
      differences. Several information is present regarding the superficial neuromasts
      of zebrafish and other teleosts especially during larval and juvenile stages,
      while not as numerous data are so far available about the ultrastructural
      characteristics of the canal neuromasts in adult zebrafish. Therefore, the aim of
      this study was to investigate by transmission electron microscopy the
      ultrastructural aspects of cells present in the canal neuromasts. Besides the
      typical cellular aspects of the neuromast, different cellular types of hair cells
      were observed that could be identified as developing hair cells during the
      physiological turnover. The knowledge of the observed cellular types of the canal
      neuromasts and their origin could give a contribution to studies carried out on
      adult zebrafish used as model in neurological and non-neurological damages, such
      as deafness and vestibular disorders.

PMID- 29582455
TI  - Pediatric Old World cutaneous leishmaniasis treated with oral fluconazole: A case
      series.
AB  - BACKGROUND: Cutaneous leishmaniasis has an incidence of 0.7-1.2 million cases per
      year and represents a growing concern in the outpatient dermatologic practice in
      Europe because of imported cases due to increased travel to risk areas and to
      immigration phenomena. When dealing with children, the treatment can be
      challenging because of side effects and pain of classic antimonial therapy
      leading to poor rates of course completion and requirement of sedation for
      several children. METHODS: We retrospectively studied three cases of cutaneous
      leishmaniasis in pediatric patients, between the ages of 3 and 6 years of age,
      treated with oral fluconazole. We examined the efficacy, the tolerability, the
      safety profile and the cosmetic result of fluconazole at a dose of 6 mg/kg/daily
      for 6 weeks. RESULTS: The patients had a complete resolution of their lesions
      with minimal scarring. No adverse effect was reported. The leishmaniasis species
      identified were L. major or L. tropica. CONCLUSION: Considering sides effects and
      the parents' and the clinician's concern for systemic treatment in the pediatric
      population, fluconazole represents a valid, safe and easily manageable option for
      Old World cutaneous leishmaniasis in pediatric outpatients caused by L. major or
      L. tropica.

PMID- 29582457
TI  - Assessing the health of internationally adopted children.

PMID- 29582456
TI  - Teaching NMR spectra analysis with nmr.cheminfo.org.
AB  - Teaching spectra analysis and structure elucidation requires students to get
      trained on real problems. This involves solving exercises of increasing
      complexity and when necessary using computational tools. Although desktop
      software packages exist for this purpose, nmr.cheminfo.org platform offers
      students an online alternative. It provides a set of exercises and tools to help
      solving them. Only a small number of exercises are currently available, but
      contributors are invited to submit new ones and suggest new types of problems.

PMID- 29582458
TI  - EPR-based oximetric imaging: a combination of single point-based spatial encoding
      and T1 weighting.
AB  - PURPOSE: Spin-lattice relaxation rate (R1 )-based time-domain EPR oximetry is
      reported for in vivo applications using a paramagnetic probe, a trityl-based
      Oxo71. METHODS: The R1 dependence of the trityl probe Oxo71 on partial oxygen
      pressure (pO2 ) was assessed using single-point imaging mode of spatial encoding
      combined with rapid repetition, similar to T1 -weighted MRI, for which R1 was
      determined from 22 repetition times ranging from 2.1 to 40.0 MUs at 300 MHz. The
      pO2 maps of a phantom with 3 tubes containing 2 mM Oxo71 solutions equilibrated
      at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin-spin relaxation
      rate ( R2*) simultaneously. RESULTS: The pO2 maps derived from R1 and R2* agreed
      with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2
      revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The
      SDs of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1 -based
      estimation than R2*-based estimation (mean +/- SD: 13.9 +/- 1.77 mmHg and 18.3 +/
      8.70 mmHg, respectively). The in vivo pO2 map obtained from R1 -based assessment
      displayed a homogeneous profile in low pO2 regions in tumor xenografts,
      consistent with previous reports on R2*-based oximetric imaging. The scan time to
      obtain the R1 map can be significantly reduced using 3 repetition times ranging
      from 4.0 to 12.0 MUs. CONCLUSION: Using the single-point imaging modality, R1 
      based oximetry imaging with useful spatial and oxygen resolutions for small
      animals was demonstrated.

PMID- 29582459
TI  - Angiomatoid and desmoplastic Spitz nevus presenting as a keloidal nodule.
AB  - Angiomatoid and desmoplastic Spitz nevi are rare histologic variants of Spitz
      nevi that present most frequently on the extremities of children and young
      adults. Although Spitz nevi are clinically heterogeneous, one presenting as a
      keloidal nodule has not been previously published. We present a case of an
      angiomatoid and desmoplastic Spitz nevus clinically akin to a keloid on an
      African-American teenager and describe its unique histopathologic features.

PMID- 29582460
TI  - Rutaecarpine attenuates osteoclastogenesis by impairing macrophage colony
      stimulating factor and receptor activator of nuclear factor kappa-B ligand
      stimulated signalling pathways.
AB  - Rutaecarpine is a major alkaloid isolated from Evodia rutaecarpa. Here, we
      investigated the effects of rutaecarpine on osteoclast differentiation induced by
      macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear
      factor kappa-B ligand (RANKL) in bone marrow-derived macrophages (BMMs).
      Treatment with rutaecarpine significantly inhibited osteoclastogenesis and
      prevented bone resorption of BMM-derived osteoclasts. Mechanistically,
      rutaecarpine decreased the protein level of nuclear factor of activated T cells
      cytoplasmic-1 (NFATc1) and the phosphorylation of other signalling pathways
      during the osteoclast differentiation. Thus, rutaecarpine may be useful as a
      therapeutic agent for the treatment of bone diseases.

PMID- 29582461
TI  - Short anagen syndrome: Case series and literature review.
AB  - BACKGROUND/OBJECTIVES: Short anagen syndrome is a hair cycle disorder usually
      diagnosed in early childhood and characterized by short hair length due to short
      duration of the anagen phase. The objective was to review the presentation and
      demographic characteristics of short anagen syndrome and compare them with the
      most common differential diagnosis, loose anagen syndrome. METHODS: A
      retrospective review of eight children with short anagen syndrome was performed
      at the University of Miami Outpatient Dermatology Clinic. RESULTS: The diagnosis
      of short anagen syndrome was confirmed according to clinical findings and
      characteristic short telogen hairs with pointed tips on the hair pull test.
      CONCLUSION: This is the largest reported clinical series of short anagen syndrome
      thus far in the literature.

PMID- 29582462
TI  - Omeprazole-induced hypertrichosis in two children.
AB  - Omeprazole significantly increases duodenal prostaglandin E2 synthesis.
      Prostaglandins are involved in hair growth regulation: prostaglandin E2 and
      prostaglandin F2 alpha stimulate hair growth, and prostaglandin D2 has an
      inhibitory effect. The use of omeprazole can cause acquired generalized
      hypertrichosis by increasing prostaglandin E2 levels.

PMID- 29582463
TI  - Software tools and tutorials in liquid state NMR.

PMID- 29582465
TI  - Tularemia-induced erythema multiforme minor in an 11-year-old girl.
AB  - Tularemia is a rare and potentially life-threatening infection caused by the
      highly infectious gram-negative coccobacillus Francisella tularensis. We present
      the case of an 11-year old girl who presented with erythema multiforme minor in
      the setting of an indolent but progressive soft tissue infection and was found to
      have tularemia. We review the role of dermatologists in identifying the features
      of and complications associated with this rare zoonosis and discuss the potential
      effect of climate change on its incidence.

PMID- 29582464
TI  - Super-resolution musculoskeletal MRI using deep learning.
AB  - PURPOSE: To develop a super-resolution technique using convolutional neural
      networks for generating thin-slice knee MR images from thicker input slices, and
      compare this method with alternative through-plane interpolation methods.
      METHODS: We implemented a 3D convolutional neural network entitled DeepResolve to
      learn residual-based transformations between high-resolution thin-slice images
      and lower-resolution thick-slice images at the same center locations. DeepResolve
      was trained using 124 double echo in steady-state (DESS) data sets with 0.7-mm
      slice thickness and tested on 17 patients. Ground-truth images were compared with
      DeepResolve, clinically used tricubic interpolation, and Fourier interpolation
      methods, along with state-of-the-art single-image sparse-coding super-resolution.
      Comparisons were performed using structural similarity, peak SNR, and RMS error
      image quality metrics for a multitude of thin-slice downsampling factors. Two
      musculoskeletal radiologists ranked the 3 data sets and reviewed the diagnostic
      quality of the DeepResolve, tricubic interpolation, and ground-truth images for
      sharpness, contrast, artifacts, SNR, and overall diagnostic quality. Mann-Whitney
      U tests evaluated differences among the quantitative image metrics, reader
      scores, and rankings. Cohen's Kappa (kappa) evaluated interreader reliability.
      RESULTS: DeepResolve had significantly better structural similarity, peak SNR,
      and RMS error than tricubic interpolation, Fourier interpolation, and sparse
      coding super-resolution for all downsampling factors (p < .05, except 4 * and 8 *
      sparse-coding super-resolution downsampling factors). In the reader study,
      DeepResolve significantly outperformed (p < .01) tricubic interpolation in all
      image quality categories and overall image ranking. Both readers had substantial
      scoring agreement (kappa = 0.73). CONCLUSION: DeepResolve was capable of
      resolving high-resolution thin-slice knee MRI from lower-resolution thicker
      slices, achieving superior quantitative and qualitative diagnostic performance to
      both conventionally used and state-of-the-art methods.

PMID- 29582466
TI  - Unique cell tropism of HHV-6B in an infantile autopsy case of primary HHV-6B
      encephalitis.
AB  - Human herpes virus 6 (HHV-6) is known to cause primary encephalitis in the
      frontal lobes/cerebral hemisphere or reactivated encephalitis in the hippocampus,
      but the pathogenesis remains unclear. HHV-6B has also been detected in
      hippocampal samples in patients with mesial temporal lobe epilepsy. A 1 year and
      3 months old female, who had been clinically diagnosed with exanthema subitum and
      febrile convulsion, was found dead on the third day after onset. Macroscopic
      findings showed massive brain edema. Microscopic examination revealed
      gemistocytic astrocytes and ballooned oligodendrocytes in the frontal white
      matter, along with neuronal cell death with microglial infiltration in the
      frontal cortex. Polymerase chain reaction detected HHV-6B in the cerebrospinal
      fluid and necropsy brain samples. The hippocampus showed a 4-5-fold increase in
      virus copy number of HHV-6B compared to samples from other brain sites.
      Immunostaining indicated that HHV-6B had infected vascular endothelial cells,
      neurons and oligodendrocytes but not astrocytes or microglia. Hippocampal neurons
      were infected with highly concentrated HHV-6B, but the hippocampus had neither
      neuronal loss nor reactive glial response. Silent and abundant HHV-6B infection
      in the hippocampus might be associated with latent infection, reactivation and
      some hippocampus-oriented disorders, including mesial temporal lobe epilepsy.

PMID- 29582467
TI  - Recent Progress in Organic Electrodes for Li and Na Rechargeable Batteries.
AB  - Organic rechargeable batteries, which use organics as electrodes, are excellent
      candidates for next-generation energy storage systems because they offer design
      flexibility due to the rich chemistry of organics while being eco-friendly and
      potentially cost efficient. However, their widespread usage is limited by
      intrinsic problems such as poor electronic conductivity, easy dissolution into
      liquid electrolytes, and low volumetric energy density. New types of organic
      electrode materials with various redox centers or molecular structures have been
      developed over the past few decades. Moreover, research aimed at enhancing
      electrochemical properties via chemical tuning has been at the forefront of
      organic rechargeable batteries research in recent years, leading to significant
      progress in their performance. Here, an overview of the current developments of
      organic rechargeable batteries is presented, with a brief history of research in
      this field. Various strategies for improving organic electrode materials are
      discussed with respect to tuning intrinsic properties of organics using molecular
      modification and optimizing their properties at the electrode level. A
      comprehensive understanding of the progress in organic electrode materials is
      provided along with the fundamental science governing their performance in
      rechargeable batteries thus a guide is presented to the optimal design strategies
      to improve the electrochemical performance for next-generation battery systems.

PMID- 29582468
TI  - Let-7c restores radiosensitivity and chemosensitivity and impairs stemness in
      oral cancer cells through inhibiting interleukin-8.
AB  - BACKGROUND: The let-7 family of microRNAs has been considered as tumor
      suppressors in various cancers; however, the role of let-7c in oral squamous cell
      carcinoma has not been determined yet. METHODS: In this study, phenotypical
      behaviors and the radio/chemoresistance were examined subsequent to
      overexpression of let-7c. In addition, the expression of let-7c in cancer stem
      cells (CSCs) was evaluated and the effect of let-7c on stemness characteristics
      was assessed. Also, luciferase activity assays were performed to test whether
      interleukin (IL)-8 was a putative target of let-7c. RESULTS: Our results
      confirmed that the expression of let-7c in CSCs was reduced, while overexpression
      of let-7c attenuated the oncogenicity. Moreover, ectopic expression of let-7c in
      CSCs downregulated the stemness hallmarks and the radio/chemoresistance.
      Expression and secretion of IL-8 in oral CSCs were both reduced following
      overexpression of let-7c. Besides, the inhibitory effect of let-7c on various
      stemness phenotypes was reverted by IL-8, indicating that lower expression of let
      7c may confer higher cancer stemness through a failure to downregulate IL-8.
      CONCLUSION: These findings revealed the significance of let-7c in the
      contribution of oral cancer stemness and radio/chemoresistance. Targeting let-7c
      and its downstream IL-8 may be beneficial to prevent cancer recurrence and
      metastasis of oral squamous cell carcinoma.

PMID- 29582469
TI  - No evidence for follicular keratinocyte hyperproliferation in acne lesions as
      compared to autologous healthy hair follicles.
AB  - Abnormal hyperkeratinization in sebaceous hair follicles has long been believed
      to play an important role in acne pathogenesis. Several early reports purported
      to provide histological evidence for hyperproliferation of keratinocytes in acne
      lesions by showing a higher expression of the Ki67 as well as certain keratins.
      The evidence is, however, not robust, and a number of methodological and
      technical limitations can be identified in these studies. In this study, we
      looked at the expression of proliferation, mitosis and apoptosis markers directly
      at acne skin lesions in 66 patients with acne vulgaris. Ki67 was assessed using
      immunohistochemistry and alpha-tubulin, phospho-histone H3 and cleaved-PARP with
      immunofluorescence microscopy. Allogenic unaffected hair follicles from the same
      acne patients were used as an internal control. In both acne and control hair
      follicles, the alpha-tubulin staining was universal, approaching 100% cells and
      showed no signs of changed assembly. Expression of cleaved-PARP-the apoptosis
      marker-was a rare event. Cell proliferation rate measured by the expression of
      Ki67 and phospho-histone H3 was virtually identical between acne and the two
      control groups. Our findings show the absence of increased keratinocyte
      proliferation in acne vulgaris. Alternative mechanisms are likely responsible for
      infundibular hyperkeratinization in acne pathogenesis.

PMID- 29582470
TI  - Considering dominance in reduced single-step genomic evaluations.
AB  - Single-step models including dominance can be an enormous computational task and
      can even be prohibitive for practical application. In this study, we try to
      answer the question whether a reduced single-step model is able to estimate
      breeding values of bulls and breeding values, dominance deviations and total
      genetic values of cows with acceptable quality. Genetic values and phenotypes
      were simulated (500 repetitions) for a small Fleckvieh pedigree consisting of 371
      bulls (180 thereof genotyped) and 553 cows (40 thereof genotyped). This pedigree
      was virtually extended for 2,407 non-genotyped daughters. Genetic values were
      estimated with the single-step model and with different reduced single-step
      models. Including more relatives of genotyped cows in the reduced single-step
      model resulted in a better agreement of results with the single-step model.
      Accuracies of genetic values were largest with single-step and smallest with
      reduced single-step when only the cows genotyped were modelled. The results
      indicate that a reduced single-step model is suitable to estimate breeding values
      of bulls and breeding values, dominance deviations and total genetic values of
      cows with acceptable quality.

PMID- 29582471
TI  - Characterization of transcriptional complexity during pre-implantation
      development of the yak (Bos grunniens) using RNA-Seq.
AB  - The objective of this study was to investigate the mechanism that regulates pre
      implantation development of the yak (Bos grunniens). We determined the
      transcriptomes of in vitro-produced yak embryos at two-cell, four-cell, eight
      cell stages, and morula and blastocyst using the Illumina RNA-seq for the first
      time. We obtained 47.36-50.86 million clean reads for each stage, of which,
      85.65%-90.02% reads were covered in the reference genome. A total of 17,368 genes
      were expressed during the two-cell stage to blastocyst of the yak, of which 7,236
      genes were co-expressed at all stages, whereas 10,132 genes were stage-specific
      expression. Transcripts from 9,827 to 14,893 different genes were detected in
      various developmental stages. When |log2 ratio| >= 1 and q-value <0.05 were set
      as thresholds for identifying differentially expressed genes (DEGs), we detected
      a total of 6,922-10,555 DEGs between any two consecutive stages. The GO
      distributions of these DEGs were classified into three categories: biological
      processes (23 terms), cellular components (22 terms) and molecular functions (22
      terms). Pathway analysis revealed 310 pathways of the DEGs that were operative in
      early pre-implantation yak development, of which 32 were the significantly
      enriched pathways. In conclusion, this is the first report to investigate the
      mechanism that regulates yak embryonic development using high-throughput
      sequencing, which provides a comprehensive framework of transcriptome landscapes
      of yak pre-implantation embryos.

PMID- 29582472
TI  - Diaryl-1,2,3-Triazolylidene Platinum(II) Complexes.
AB  - Control of the excited state geometry by rational ligand design leads to a new
      class of phosphorescent emitters with extraordinary photophysical properties.
      Extension of the pi-system in the triplet state leading to a significant
      bathochromic shift of the emission was avoided by introduction of additional
      steric demand. We report the synthesis, characterization and photophysical
      properties of novel platinum(II) complexes bearing C^C* cyclometalated mesoionic
      carbene (MIC) with different beta-diketonate ligands. The MIC ligand precursors
      were prepared from 1-phenyl-1,2,3-triazole using arylation protocols, introducing
      phenyl or mesityl functionalities. A solid state structure confirming the NMR
      assignments is presented. The emission properties were investigated in detail at
      room temperature and 77 K and are supported by DFT calculations and cyclic
      voltammetry. All complexes, with emission maxima between 502-534 nm, emit with
      quantum efficiencies ranging from 70-84 % in PMMA films.

PMID- 29582473
TI  - Prolactin as a candidate sebotrop(h)ic hormone?
AB  - Recognised for its key role in lactation, it is less well appreciated that the
      neurohormone prolactin (PRL) is actually one of the most pleiotropic hormones
      known. Not only does PRL exert both tropic and trophic effects in a wide range of
      tissues, but it is also expressed in human skin and hair follicles and regulates
      multiple complex cutaneous functions, including keratin expression and hair
      growth. Despite several clinical indications that PRL may also play a role in
      sebaceous gland (SG) biology, the effects of PRL on SG function have received
      little attention. In this Viewpoint essay, we argue that PRL may be a
      sebotrop(h)ic hormone and could represent a novel therapeutic target in human
      dermatoses affecting the SG. We provide preliminary evidence in support of this
      hypothesis (based on findings in human skin organ culture) and chart the major
      open questions in SG biology and pathology from a PRL research perspective. We
      close by delineating how these questions can be experimentally addressed so as to
      identify new therapeutic strategies that are either sebogenic or sebostatic, for
      example in the management of acne and cutaneous ageing.

PMID- 29582474
TI  - Dual kidney transplantation as a strategy to use expanded criteria donors: a
      systematic review.
AB  - The objective of this review was to assess whether dual kidney transplantation
      (DKT) is better than single KT (SKT) for optimizing the use of expanded criteria
      donor kidneys. We did a systematic literature search and meta-analyses when
      possible, pooling data for calculating relative risks (RR) of major outcomes.
      Twenty-five studies met the inclusion criteria. One-year serum creatinine was
      better after DKT vs. SKT (mean difference -0.27 [-0.37, -0.17], P < 0.001), with
      less incidence of acute rejection (RR 0.66 [0.52, 0.85], P < 0.001) and without
      differences at five years. Less DGF was seen in DKT (RR 0.88 [0.76, 1.02], P =
      0.09). Mortality at 1 and 3 years was similar after dual or SKT, but mortality at
      five years was lower after DKT (RR 0.71 [0.53, 0.94], P = 0.02). One-year graft
      loss was similar between dual (n = 4158) and SKT (n = 51 800) (RR 0.97 [0.87,
      1.09], P = 0.62). Three- and five-year graft loss was not considered because of
      high heterogeneity between studies. In conclusion, short-term graft function and
      long-term patient survival are better in recipients receiving DKT vs. SKT.
      However, these differences are based on few retrospective reports with a
      relatively low number of cases. Good quality randomized controlled trials are
      needed to assess whether the investment of two kidneys in one recipient is
      justified in face of the current organ shortage.

PMID- 29582475
TI  - First-in-human experience of left atrial appendage occlusion with the steerable
      FuStar sheath.
AB  - BACKGROUND: Due the wide variability of left atrial appendage morphology left
      atrial appendage occlusion (LAAO) remains a challenging procedure. The steerable
      FuStar delivery sheath was designed to allow both, transseptal access and
      delivery of percutaneous devices. We here report the first-in-human experience of
      LAAO with the FuStar sheath. METHODS: Twenty patients (76.6 +/- 8.4 years; 12
      (60%) males; CHA2 DS2 -VASc score: 5.0 +/- 2) with non-valvular fibrillation and
      contraindications to oral anticoagulation underwent LAAO with the LAmbre device
      using the FuStar steerable sheath (Lifetech Scientific Corp., Shenzhen, China) at
      two german centers. RESULTS: Successful device implantation was achieved in all
      patients (100%). No periprocedural complications were observed. Procedure time,
      fluoroscopy time, contrast media, and radiation dose were 23.4 min +/- 9.2, 11.9
      min +/- 4.1, 96.2 mL +/- 45.7, and 2718.4 cG*cm2  +/- 3835.3, respectively.
      CONCLUSION: This study demonstrates the feasibility and safety of the steerable
      FuStar sheath for LAAO.

PMID- 29582477
TI  - Immune molecular profiling of whole blood drawn from a non-human primate cardiac
      xenograft model treated with anti-CD154 monoclonal antibodies.
AB  - Most studies of xenografts have been carried out with complex immunosuppressive
      regimens to prevent immune rejection; however, such treatments may be fatal owing
      to unknown causes. Here, we performed immune molecular profiling following anti
      CD154 monoclonal antibody (mAb) treatment in heterotopic abdominal cardiac
      xenografts from alpha-1,3-galactosyltransferase-knockout pigs into cynomolgus
      monkeys to elucidate the mechanisms mediating the undesirable fatal side effects
      of immunosuppressive agents. Blood samples were collected from healthy monkeys as
      control and then at 2 days after xenograft transplantation and just before humane
      euthanasia; 94 genes related to the immune system were analyzed. The basic
      immunosuppressive regimen included cobra venom factor, anti-thymocyte globulin,
      and rituximab, with and without anti-CD154 mAbs. The maintenance therapy was
      followed with tacrolimus, MMF, and methylprednisolone. The number of upregulated
      genes was initially decreased on Day 2 (-/+ anti-CD154 mAb, 22/13) and then
      increased before euthanasia in recipients treated with anti-CD154 mAbs (-/+ anti
      CD154 mAb, 30/37). The number of downregulated genes was not affected by anti
      CD154 mAb treatment. Additionally, the number of upregulated genes increased over
      time for both groups. Interestingly, treatment with anti-CD154 mAbs upregulated
      coagulation inducers (CCL2/IL6) before euthanasia. In conclusion,
      immunosuppressive regimens used for cardiac xenografting affected upregulation of
      6 inflammation genes (CXCL10, MPO, MYD88, NLRP3, TNFalpha, and TLR1) and
      downregulation of 8 genes (CCR4, CCR6, CD40, CXCR3, FOXP3, GATA3, STAT4, and
      TBX21).

PMID- 29582478
TI  - Advanced Materials by Atom Transfer Radical Polymerization.
AB  - Atom transfer radical polymerization (ATRP) has been successfully employed for
      the preparation of various advanced materials with controlled architecture. New
      catalysts with strongly enhanced activity permit more environmentally benign ATRP
      procedures using ppm levels of catalyst. Precise control over polymer
      composition, topology, and incorporation of site specific functionality enables
      synthesis of well-defined gradient, block, comb copolymers, polymers with
      (hyper)branched structures including stars, densely grafted molecular brushes or
      networks, as well as inorganic-organic hybrid materials and bioconjugates.
      Examples of specific applications of functional materials include thermoplastic
      elastomers, nanostructured carbons, surfactants, dispersants, functionalized
      surfaces, and biorelated materials.

PMID- 29582476
TI  - Cell Membrane Coating Nanotechnology.
AB  - Nanoparticle-based therapeutic, prevention, and detection modalities have the
      potential to greatly impact how diseases are diagnosed and managed in the clinic.
      With the wide range of nanomaterials available, the rational design of
      nanocarriers on an application-specific basis has become increasingly
      commonplace. Here, a comprehensive overview is provided on an emerging platform:
      cell-membrane-coating nanotechnology. As a fundamental unit of biology, cells
      carry out a wide range of functions, including the remarkable ability to
      interface and interact with their surrounding environment. Instead of attempting
      to replicate such functions via synthetic techniques, researchers are now
      directly leveraging naturally derived cell membranes as a means of bestowing
      nanoparticles with enhanced biointerfacing capabilities. This top-down technique
      is facile, highly generalizable, and has the potential to greatly augment
      existing nanocarriers. Further, the introduction of a natural membrane substrate
      onto nanoparticles surfaces has enabled additional applications beyond those
      traditionally associated with nanomedicine. Despite its relative youth, there
      exists an impressive body of literature on cell membrane coating, which is
      covered here in detail. Overall, there is still significant room for development,
      as researchers continue to refine existing workflows while finding new and
      exciting applications that can take advantage of this developing technology.

PMID- 29582479
TI  - Comparative assessment of growth performance of three different indigenous goat
      breeds exposed to summer heat stress.
AB  - A study was conducted to assess comparatively the growth performance of three
      different indigenous goat breeds during exposure to summer heat stress. The
      primary objective of the study was to observe the heat stress impact on the
      growth performance based on the body weight changes, allometric measurements,
      growth hormone (GH) concentration and peripheral blood mononuclear cell (PBMC)
      Insulin-like growth factor-1 (IGF-1) mRNA expression pattern during the summer
      season in comparison with the local breed (Osmanabadi). Thirty-six ten-month- to
      one-year-old female goats of Osmanabadi, Malabari and Salem Black breeds were
      randomly divided into six groups, OC (n = 6; Osmanabadi control), OHS (n = 6;
      Osmanabadi heat stress), MC (n = 6; Malabari control), MHS (n = 6; Malabari heat
      stress), SBC (n = 6; Salem Black control) and SBHS (n = 6; Salem Black heat
      stress). Body weight was recorded at weekly intervals, whereas other growth and
      allometric measurements and blood collection were carried out at fortnightly
      intervals. Breed factor significantly (p < .05) influenced only few growth
      variables such as body weight, body mass index (BMI) and body condition score
      (BCS). However, heat stress treatment significantly (p < .05) reduced all growth
      parameters expect BMI. Further, the heat stress significantly (p < .01) increased
      plasma GH concentration in goats with significantly higher (p < .05)
      concentration recorded in OHS. Among the stress groups, the lower (p < .05) PBMC
      IGF-1 mRNA expression was recorded in OHS, while the higher (p < .05) expression
      was observed in SBHS indicating the extreme adaptive capability of Salem Black
      breed. Thus, the results indicated that the Salem Black breed performed much
      better compared to both Osmanabadi and Malabari breeds indicating the superior
      ability of this breed to adapt to heat stress challenges. The results also
      indicated that plasma GH and IGF-1 gene may act as ideal biomarkers for assessing
      the heat stress impact on growth performance in indigenous goats.

PMID- 29582482
TI  - Metal-Organic Frameworks for Separation.
AB  - Separation is an important industrial step with critical roles in the chemical,
      petrochemical, pharmaceutical, and nuclear industries, as well as in many other
      fields. Although much progress has been made, the development of better
      separation technologies, especially through the discovery of high-performance
      separation materials, continues to attract increasing interest due to concerns
      over factors such as efficiency, health and environmental impacts, and the cost
      of existing methods. Metal-organic frameworks (MOFs), a rapidly expanding family
      of crystalline porous materials, have shown great promise to address various
      separation challenges due to their well-defined pore size and unprecedented
      tunability in both composition and pore geometry. In the past decade, extensive
      research is performed on applications of MOF materials, including separation and
      capture of many gases and vapors, and liquid-phase separation involving both
      liquid mixtures and solutions. MOFs also bring new opportunities in
      enantioselective separation and are amenable to morphological control such as
      fabrication of membranes for enhanced separation outcomes. Here, some of the
      latest progress in the applications of MOFs for several key separation issues,
      with emphasis on newly synthesized MOF materials and the impact of their
      compositional and structural features on separation properties, are reviewed and
      highlighted.

PMID- 29582480
TI  - Evaluation of updated sepsis scoring systems and systemic inflammatory response
      syndrome criteria and their association with sepsis in equine neonates.
AB  - BACKGROUND: The original equine sepsis score provided a method of identifying
      foals with sepsis. New variables associated with sepsis have been evaluated, but
      the sepsis score has not been updated. OBJECTIVES: To evaluate the sensitivity
      and specificity of 2 updated sepsis scores and the systemic inflammatory response
      syndrome (SIRS) criteria in regard to detecting sepsis in foals. ANIMALS: Two
      hundred and seventy-three ill foals and 25 healthy control foals. METHODS:
      Historical, physical examination, and clinicopathologic findings were used to
      calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria
      were also evaluated. Sepsis scores and positive SIRS scores were statistically
      compared to foals with sepsis. RESULTS: One-hundred and twenty-six foals were
      septic and 147 sick-nonseptic. The original and updated sepsis scores were
      significantly higher in septic foals as compared to sick-nonseptic and healthy
      foals. The sensitivity and specificity of the updated sepsis scores to predict
      sepsis were not significantly better than those of the original sepsis score. One
      hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and
      88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS
      criteria had similar sensitivity and specificity for predicting sepsis as did the
      3 sepsis scores in our study. CONCLUSIONS AND CLINICAL IMPORTANCE: The updated
      sepsis scores did not provide improved ability in predicting sepsis. Fulfilling
      the original SIRS criteria provided similar sensitivity and specificity in
      predicting sepsis as the modified sepsis score and might serve as a diagnostic
      aid in identifying foals at risk for sepsis.

PMID- 29582481
TI  - Resveratrol-cyclodextrin complex affects the expression of genes associated with
      lipid metabolism in bovine in vitro produced embryos.
AB  - Antioxidants have been widely used during in vitro production to decrease the
      negative effect of reactive oxygen species. It was reported that the complex
      resveratrol-methyl beta-cyclodextrin (RV-CD) improves resveratrol's stability and
      bioavailability and increases its antioxidant activity. This study evaluates the
      effect of RV-CD during in vitro oocyte maturation (IVM) or in vitro embryo
      culture (IVC) on developmental competence and quantitative changes in gene
      expression of developmental important genes. In experiment 1, RV-CD was added to
      IVM media and maturation level, embryo development and oocytes, cumulus cells,
      and blastocysts gene expression by RT-qPCR were examined. In experiment 2,
      presumptive zygotes were cultured in SOF supplemented with RV-CD and embryo
      development and blastocysts gene expression by RT-qPCR were studied. A group
      without RV-CD (control- ) and a group with cyclodextrin (control+ ) were
      included. No differences were found in cleavage rate or blastocyst yield between
      groups. However, the expression of LIPE was higher in blastocysts derived from
      oocytes treated with resveratrol compared with control groups (p < .05).
      Blastocysts produced by IVC with resveratrol showed that RV-CD could modify the
      expression of genes related to lipid metabolism (CYP51A1, PNPLA2 and MTORC1)
      compared with control groups (p < .05). RV-CD in the IVM and IVC media could
      reduce accumulated fat by increasing lipolysis and suppressing lipogenesis of
      blastocysts.

PMID- 29582483
TI  - Stretchable All-Gel-State Fiber-Shaped Supercapacitors Enabled by
      Macromolecularly Interconnected 3D Graphene/Nanostructured Conductive Polymer
      Hydrogels.
AB  - Nanostructured conductive polymer hydrogels (CPHs) have been extensively applied
      in energy storage owing to their advantageous features, such as excellent
      electrochemical activity and relatively high electrical conductivity, yet the
      fabrication of self-standing and flexible electrode-based CPHs is still hampered
      by their limited mechanical properties. Herein, macromolecularly interconnected
      3D graphene/nanostructured CPH is synthesized via self-assembly of CPHs and
      graphene oxide macrostructures. The 3D hybrid hydrogel shows uniform
      interconnectivity and enhanced mechanical properties due to the strong
      macromolecular interaction between the CPHs and graphene, thus greatly reducing
      aggregation in the fiber-shaping process. A proof-of-concept all-gel-state
      fibrous supercapacitor based on the 3D polyaniline/graphene hydrogel is
      fabricated to demonstrate the outstanding flexibility and mouldability, as well
      as superior electrochemical properties enabled by this 3D hybrid hydrogel design.
      The proposed device can achieve a large strain (up to ~40%), and deliver a
      remarkable volumetric energy density of 8.80 mWh cm-3 (at power density of 30.77
      mW cm-3 ), outperforming many fiber-shaped supercapacitors reported previously.
      The all-hydrogel design opens up opportunities in the fabrication of next
      generation wearable and portable electronics.

PMID- 29582484
TI  - Covalent Organic Frameworks as a Decorating Platform for Utilization and Affinity
      Enhancement of Chelating Sites for Radionuclide Sequestration.
AB  - The potential consequences of nuclear events and the complexity of nuclear waste
      management motivate the development of selective solid-phase sorbents to provide
      enhanced protection. Herein, it is shown that 2D covalent organic frameworks
      (COFs) with unique structures possess all the traits to be well suited as a
      platform for the deployment of highly efficient sorbents such that they exhibit
      remarkable performance, as demonstrated by uranium capture. The chelating groups
      laced on the open 1D channels exhibit exceptional accessibility, allowing
      significantly higher utilization efficiency. In addition, the 2D extended
      polygons packed closely in an eclipsed fashion bring chelating groups in adjacent
      layers parallel to each other, which may facilitate their cooperation, thereby
      leading to high affinity toward specific ions. As a result, the amidoxime
      functionalized COFs far outperform their corresponding amorphous analogs in terms
      of adsorption capacities, kinetics, and affinities. Specifically, COF-TpAb-AO is
      able to reduce various uranium contaminated water samples from 1 ppm to less than
      0.1 ppb within several minutes, well below the drinking water limit (30 ppb), as
      well as mine uranium from spiked seawater with an exceptionally high uptake
      capacity of 127 mg g-1 . These results delineate important synthetic advances
      toward the implementation of COFs in environmental remediation.

PMID- 29582485
TI  - Uniaxial Alignment of Conjugated Polymer Films for High-Performance Organic Field
      Effect Transistors.
AB  - Polymer semiconductors have been experiencing a remarkable improvement in
      electronic and optoelectronic properties, which are largely related to the recent
      development of a vast library of high-performance, donor-acceptor copolymers
      showing alternation of chemical moieties with different electronic affinities
      along their backbones. Such steady improvement is making conjugated polymers even
      more appealing for large-area and flexible electronic applications, from
      distributed and portable electronics to healthcare devices, where cost-effective
      manufacturing, light weight, and ease of integration represent key benefits.
      Recently, a strong boost to charge carrier mobility in polymer-based field-effect
      transistors, consistently achieving the range from 1.0 to 10 cm2 V-1 s-1 for both
      holes and electrons, has been given by uniaxial backbone alignment of polymers in
      thin films, inducing strong transport anisotropy and favoring enhanced transport
      properties along the alignment direction. Herein, an overview on this topic is
      provided with a focus on the processing-structure-property relationships that
      enable the controlled and uniform alignment of polymer films over large areas
      with scalable processes. The key aspects are specific molecular structures, such
      as planarized backbones with a reduced degree of conformational disorder,
      solution formulation with controlled aggregation, and deposition techniques
      inducing suitable directional flow.

PMID- 29582486
TI  - Unusual Circularly Polarized and Aggregation-Induced Near-Infrared
      Phosphorescence of Helical Platinum(II) Complexes with Tetradentate Salen
      Ligands.
AB  - A series of chiral and helical PtII -Salen complexes with 1,1'-binaphthyl linkers
      were synthesized and characterized. Owing to the restriction of intramolecular
      motions of central 1,1'-binaphthyls, the complexes exhibit unusual near-infrared
      aggregation-induced phosphorescence (AIP). The (R)/(S) enantiopure complexes were
      characterized by X-ray diffraction, circular dichroism spectra, time-dependent
      density functional theory calculations, and circularly polarized luminescence
      (CPL). The present work explores the use of tetradentate ligands that can be
      easily prepared from commercially available enantiopure compounds, and the
      subsequent preparation of stable CPL-active square planar PtII complexes with AIP
      effect that may have interest in many applications.

PMID- 29582487
TI  - Protein Bricks: 2D and 3D Bio-Nanostructures with Shape and Function on Demand.
AB  - Precise patterning of polymer-based biomaterials for functional bio
      nanostructures has extensive applications including biosensing, tissue
      engineering, and regenerative medicine. Remarkable progress is made in both top
      down (based on lithographic methods) and bottom-up (via self-assembly) approaches
      with natural and synthetic biopolymers. However, most methods only yield 2D and
      pseudo-3D structures with restricted geometries and functionalities. Here, it is
      reported that precise nanostructuring on genetically engineered spider silk by
      accurately directing ion and electron beam interactions with the protein's matrix
      at the nanoscale to create well-defined 2D bionanopatterns and further assemble
      3D bionanoarchitectures with shape and function on demand, termed "Protein
      Bricks." The added control over protein sequence and molecular weight of
      recombinant spider silk via genetic engineering provides unprecedented
      lithographic resolution (approaching the molecular limit), sharpness, and
      biological functions compared to natural proteins. This approach provides a
      facile method for patterning and immobilizing functional molecules within
      nanoscopic, hierarchical protein structures, which sheds light on a wide range of
      biomedical applications such as structure-enhanced fluorescence and biomimetic
      microenvironments for controlling cell fate.

PMID- 29582488
TI  - Binaural responses in the auditory midbrain of chicken (Gallus gallus).
AB  - The auditory midbrain is the location in which neurons represent binaural
      acoustic information necessary for sound localization. The external nucleus of
      the midbrain inferior colliculus (IC) of the barn owl is a classic example of an
      auditory space map, but it is unknown to what extent the principles underlying
      its formation generalize to other, less specialized animals. We characterized the
      spiking responses of 139 auditory neurons in the IC of the chicken (Gallus
      gallus) in vivo, focusing on their sensitivities to the binaural localization
      cues of interaural time (ITD) and level (ILD) differences. Most units were
      frequency-selective, with best frequencies distributed unevenly into low
      frequency and high-frequency (> 2 kHz) clusters. Many units showed sensitivity to
      either ITD (65%) or ILD (66%) and nearly half to both (47%). ITD selectivity was
      disproportionately more common among low-frequency units, while ILD-only
      selective units were predominantly tuned to high frequencies. ILD sensitivities
      were diverse, and we thus developed a decision tree defining five types. One rare
      type with a bell-like ILD tuning was also selective for ITD but typically not
      frequency-selective, and thus matched the characteristics of neurons in the
      auditory space map of the barn owl. Our results suggest that generalist birds
      such as the chicken show a prominent representation of ITD and ILD cues in the
      IC, providing complementary information for sound localization, according to the
      duplex theory. A broadband response type narrowly selective for both ITD and ILD
      may form the basis for a representation of auditory space.

PMID- 29582489
TI  - Universal prevention of alcohol and drug use: An overview of reviews in an
      Australian context.
AB  - ISSUES: This overview of reviews will synthesise information from existing
      reviews to provide a summary of the evidence for universal alcohol and illicit
      drug prevention strategies across different intervention settings. APPROACH:
      Academic databases, including Medline, EMBASE and PsycInfo were searched on 1
      August 2016. All reviews and meta-analyses of universal alcohol and drug
      prevention conducted since 2006 were included. The reviews included in this
      overview were grouped according to the different settings where prevention
      strategies have been applied (i.e. family, school, college, workplace, leisure,
      healthcare, community, media and policy). KEY FINDINGS: Fifty-two reviews met the
      inclusion criteria and were included in this report. There is sufficient evidence
      to support universal preventive interventions for alcohol in family and school
      settings. In terms of reducing drug use, there is sufficient evidence to support
      the use of school- and leisure-based universal primary prevention strategies.
      Based on evidence published in the last 10 years, mass media campaigns to do not
      appear to be effective in reducing drug use. More evidence is needed to support
      preventive interventions in college, workplace, healthcare and community
      settings. IMPLICATIONS: Through the identification of settings where preventive
      interventions are effective, this overview can be used to guide alcohol and drug
      policy and the allocation of resources. CONCLUSION: The evidence base for
      universal prevention in several settings could be strengthened, guiding
      priorities for future research.

PMID- 29582490
TI  - Expanding the Schulze-Hardy Rule and the Hofmeister Series to Nanometer-Scaled
      Hydrophilic Macroions.
AB  - The Schulze-Hardy rule is a well-established observation in colloid science (can
      be derived from the DLVO theory) that demonstrates the relationship between the
      critical coagulation concentration (CCC) of colloids and the valence of extra
      counterionic electrolytes (z), with a simple mathematical relationship of CCC~z-6
      . Here the Schulze-Hardy Rule is expanded to much smaller, nano-scaled soluble
      macroions in aqueous solution, by examining the stability of the macroions in the
      presence of additional electrolytes. The CCC values of the macroions follow the
      general trend of CCC~z-n but the n value is significantly dependent on the
      surface charge density of the macroions, ranging from n=2 at very low surface
      charge density to n=6 at a high surface charge density. In addition, different
      cations with the same valence showed clear different impacts on the CCC values,
      with an interesting trend being connected to the Hofmeister series originally
      discovered in protein solutions.

PMID- 29582491
TI  - Fecal flotation in the detection of canine Demodex mites.

PMID- 29582492
TI  - Long non-coding RNAs in melanoma.
AB  - Melanoma is the most lethal cutaneous cancer with a highly aggressive and
      metastatic phenotype. While recent genetic and epigenetic studies have shed new
      insights into the mechanism of melanoma development, the involvement of
      regulatory non-coding RNAs remain unclear. Long non-coding RNAs (lncRNAs) are a
      group of endogenous non-protein-coding RNAs with the capacity to regulate gene
      expression at multiple levels. Recent evidences have shown that lncRNAs can
      regulate many cellular processes, such as cell proliferation, differentiation,
      migration and invasion. In the melanoma, deregulation of a number of lncRNAs,
      such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY-IT1 and SAMMSON, have been reported.
      Our review summarizes the functional role of lncRNAs in melanoma and their
      potential clinical application for diagnosis, prognostication and treatment.

PMID- 29582493
TI  - Hydrogenation of Fluorographite and Fluorographene: An Easy Way to Produce Highly
      Hydrogenated Graphene.
AB  - Fluorographene is an excellent precursor for the synthesis of graphene
      derivatives. Relative to pure graphene, fluorographene possesses higher
      reactivity and, in comparison with graphene oxide, is also homogenous in
      composition, which enables the preparation of well-defined materials. Recently,
      it has been shown that several graphene derivatives can be synthesized from
      fluorographene, thus yielding various products such as graphene acid or alkylated
      graphene. This study focuses on the hydrogenation of fluorographene by using
      various hydrogenation reactions, including the use complex hydrides and solvated
      electrons in different media. In addition, a comparison of these reactions shows
      that fluorinated graphite has significantly lower reactivity than fluorographene.
      The conversion rates of these reactions are higher when fluorographene is used
      relative to fluorographite. These reactions can be used to tune the
      hydrogen/fluorine composition on a graphene backbone.

PMID- 29582495
TI  - Targeting Alzheimer's disease with gene and cell therapies.
AB  - Alzheimer's disease (AD) causes dementia in both young and old people affecting
      more than 40 million people worldwide. The two neuropathological hallmarks of the
      disease, amyloid beta (Abeta) plaques and neurofibrillary tangles consisting of
      protein tau are considered the major contributors to the disease. However, a more
      complete picture reveals significant neurodegeneration and decreased cell
      survival, neuroinflammation, changes in protein and energy homeostasis and
      alterations in lipid and cholesterol metabolism. In addition, gene and cell
      therapies for severe neurodegenerative disorders have recently improved
      technically in terms of safety and efficiency and have translated to the clinic
      showing encouraging results. Here, we review broadly current data within the
      field for potential targets that could modify AD through gene and cell therapy
      strategies. We envision that not only Abeta will be targeted in a disease
      modifying treatment strategy but rather that a combination of treatments,
      possibly at different intervention times may prove beneficial in curing this
      devastating disease. These include decreased tau pathology, neuronal growth
      factors to support neurons and modulation of neuroinflammation for an appropriate
      immune response. Furthermore, cell based therapies may represent potential
      strategies in the future.

PMID- 29582494
TI  - 1,2,4-trihydroxynaphthalene-2-O-beta-D-glucopyranoside delays amyloid-beta42
      aggregation and reduces amyloid cytotoxicity.
AB  - Presently, misfolding and aggregation of amyloid-beta42 (Abeta42 ) are considered
      early events in Alzheimer's disease (AD) pathogenesis. The use of natural
      products to inhibit the aggregation process and to protect cells from
      cytotoxicity of early aggregate grown at the onset of the aggregation path is one
      of the promising strategies against AD. Recently, we have purified a new powerful
      antioxidant and inhibitor of Abeta42 aggregation from the leaves of Lawsonia
      inermis. The new compound was identified as a new Lawsoniaside; 1,2,4
      trihydroxynaphthalene-2-O-beta-D-glucopyranoside (THNG). Herein, we show that
      THNG interferes with Abeta42 aggregation, inhibits its conformational change to a
      beta-sheet-rich structure, decreases its polymerization into large fibrillar
      species, reduces oxidative stress, and aggregate cytotoxicity. These results
      indicate that THNG has great potential as a neuroprotective and therapeutic agent
      against AD. (c) 2018 BioFactors, 44(3):272-280, 2018.

PMID- 29582496
TI  - Availability of alcohol: Location, time and ease of purchase in high- and middle
      income countries: Data from the International Alcohol Control Study.
AB  - INTRODUCTION AND AIMS: Cross-country studies on alcohol purchasing and access are
      rare. We examined where and when people access alcohol to understand patterns of
      availability across a range of middle- and high-income countries. DESIGN AND
      METHODS: Surveys of drinkers in the International Alcohol Control study in high
      income countries (Australia, England, Scotland, New Zealand and St Kitts and
      Nevis) and middle-income countries (Mongolia, South Africa, Peru, Thailand and
      Vietnam) were analysed. Measures were: location of purchase from on-premise and
      take-away outlets, proportion of alcohol consumed on-premise versus take-away
      outlets, hours of purchase, access among underage drinkers and time to access
      alcohol. RESULTS: On-premise purchasing was prevalent in the high-income
      countries. However, the vast majority of alcohol consumed in all countries,
      except St Kitts and Nevis (high-income), was take-away. Percentages of drinkers
      purchasing from different types of on-premise and take-away outlets varied
      between countries. Late purchasing was common in Peru and less common in Thailand
      and Vietnam. Alcohol was easily accessed by drinkers in all countries, including
      underage drinkers in the middle-income countries. DISCUSSION AND CONCLUSIONS: In
      nine out of 10 countries the vast majority of alcohol consumed was take-away.
      Alcohol was readily available and relatively easy for underage drinkers to
      access, particularly in the middle-income countries. Research is needed to assess
      the harms associated with take-away consumption including late at night.
      Attention is needed to address the easy access by underage drinkers in the middle
      income countries which has been less of a focus than in high-income countries.

PMID- 29582497
TI  - Emergency department risk factors for serious clinical deterioration in a
      paediatric hospital in Peru.
AB  - AIM: Identification of critically ill children upon presentation to the emergency
      department (ED) is challenging, especially when resources are limited. The
      objective of this study was to identify ED risk factors associated with serious
      clinical deterioration (SCD) during hospitalisation in a resource-limited
      setting. METHODS: A retrospective case-control study of children less than 18
      years of age presenting to the ED in a large, freestanding children's hospital in
      Peru was performed. Cases had SCD during the first 7 days of hospitalisation
      whereas controls did not. Information collected during initial ED evaluation was
      used to identify risk factors for SCD. RESULTS: A total of 120 cases and 974
      controls were included. In univariate analysis, young age, residence outside
      Lima, evaluation at another facility prior to ED presentation, congenital
      malformations, abnormal neurologic baseline, co-morbidities and a prior
      paediatric intensive care unit admission were associated with SCD. In
      multivariate analysis, age < 12 months, residence outside Lima and evaluation at
      another facility prior to ED presentation remained associated with SCD. In
      addition, comatose neurological status, hypoxaemia, tachycardia, tachypnoea and
      temperature were also associated with SCD. CONCLUSIONS: Many risk factors for SCD
      during hospitalisation can be identified upon presentation to the ED. Using these
      factors to adjust monitoring during and after the ED stay has the potential to
      decrease SCD events. Further studies are needed to determine whether this holds
      true in other resource-limited settings.

PMID- 29582498
TI  - Requirement of Leptinotarsa decemlineata gene within the 74EF puff for larval
      pupal metamorphosis and appendage growth.
AB  - Two Drosophila melanogaster E-twenty-six domain transcription factor isoforms
      (E74A and E74B) act differentially at the start of the 20-hydroxyecdysone (20E)
      signalling cascade to regulate larval-pupal metamorphosis. In the present paper,
      we identified the two isoforms (LdE74A and LdE74B) in Leptinotarsa decemlineata.
      During the larval development stage, the mRNA transcript levels of the two LdE74
      isoforms were correlated with circulating 20E titres. In vitro midgut culture and
      in vivo dietary supplementation with 20E revealed that the presence of 20E
      induced expression peaks of both LdE74A and LdE74B, with similar patterns
      observed for the two isoforms. Moreover, the mRNA transcript levels of both
      LdE74A and LdE74B isoforms were significantly downregulated in the L.
      decemlineata ecdysone receptor RNA interference (RNAi) specimens, but not in the
      LdE75 RNAi beetles. Ingestion of 20E reduced the larval fresh weights and
      shortened the larval development period, irrespective of knockdown of LdE74 or
      not. RNAi of LdE74 did not affect 20E-induced expression of the Ecdysone induced
      protein 75-hormone receptor 3-fushi tarazu factor 1 (E75-HR3-FTZ-F1)
      transcriptional cascade. Thus, it seems that LdE74 mediates 20E signalling
      independent of the E75-HR3-FTZ-F1 transcriptional cascade. Furthermore, silencing
      of both LdE74 isoforms caused failure of ecdysis. Most of the LdE74 RNAi beetles
      remained as prepupae. The LdE74 RNAi prepupae exhibited adult character-like
      forms underneath after removal of the apolysed larval cuticle. Their appendages
      such as antennae, legs and wings were shorter than those of control larvae. Only
      a few LdE74 RNAi larvae finally became deformed pupae, with shortened antennae
      and legs. Therefore, LdE74 is required for larval-pupal metamorphosis and
      appendage growth in L. decemlineata.

PMID- 29582499
TI  - Knowledge and behaviors in relation to antibiotic use among rural residents in
      Anhui, China.
AB  - OBJECTIVES: To examine antibiotic-related knowledge and behaviors in rural Anhui,
      identify factors associated with knowledge, and explore the relationship between
      knowledge and antibiotic use. METHODS: Cross-sectional study of a random sample
      of 2760 residents of rural China using structured interviews. RESULTS: The
      response rate was 94.6%. A total of 2390 respondents (91.6%) believed that
      antibiotics can control viruses; 2007 (77.5%) respondents thought that a
      combination of antibiotics is more effective than a single class; and 590 (22.6%)
      were able to name at least one disbenefit of using antibiotics. Multivariate
      analysis revealed those with a higher educational level and younger age group had
      greater knowledge of antibiotics (OR 2.54 and 0.77, respectively). Self
      medication was common with 1052 (out of 2274 responses, 46.3%) of participants
      use over the counter or leftover medicines for common infections. Greater
      knowledge was associated with buying drugs without prescription (aOR 2.02; 95%
      CI, 1.29-3.17) and using leftover medication (aOR 2.80; 95% CI, 1.55-5.06).
      CONCLUSION: Knowledge about antibiotics was low and reported use high. Worryingly
      those with greater knowledge had less desirable behaviors that highlights the
      urgent need for multifaceted interventions to change behavior.

PMID- 29582500
TI  - The stereodynamics of macrocyclic succinimide-thioethers.
AB  - Maleimide-thiol coupling is a popular bioconjugation strategy, but little is
      known about the stereoselectivity and the stereodynamics of the succinimide
      thioether formed in a biopolymer environment. We used thiol 1,4-addition for the
      macrocyclisation of 5 designed pentapeptides with the ringsize of hexapeptides
      because they incorporate the succinimide thioether (4-8). Both succinimide
      diastereomers are observed in the constrained macrocyclic rings in each case. In
      spite of the low diastereoselectivity of the macrocyclisation reaction, there is
      a significant influence of the amino acid environment on the epimerization rate
      of the succinimide. Its half life can be as short as several hours at room
      temperature when Gly is the amino acid following the succinimide (peptide 8). On
      the contrary, no epimerization is detectable even after several weeks in the case
      of d-Phe C-terminal to the succinimide in peptide 4. Already the small selection
      of examples shows how big the differences in epimerization rates can be and that
      the local environment has a significant influence. The variation of amino acids
      in the vicinity of the ligation site points the way towards the synthesis of
      bioconjugates which are obtained as stable and separable diastereomers.

PMID- 29582501
TI  - The symbolic representation of community in social isolation and loneliness among
      older people: Insights for intervention from a rural Irish case study.
AB  - Social isolation and loneliness are common experiences of ageing in rural
      communities. Policy responses and interventions for social isolation and
      loneliness in later life are shaped by sociocultural understandings of place,
      relationships and social interaction. This study examined how representations of
      rural community in Ireland influenced the focus, relationships and activities
      within a befriending intervention designed to tackle social isolation and
      loneliness. Through a qualitative case study conducted in 2014, the symbolic
      meaning of the intervention was explored using interviews and focus groups with
      participants (8 befriended, 11 befrienders and 3 community workers) from one
      befriending programme in rural Ireland. Reflected in the programme was a
      representation of a rural community in decline with concern for the impact on
      older people. There was a valuing of the traditional community defined by
      geographical place, perceptions of similarity among its members, and values of
      solidarity and mutual support. The befriending intervention represented a
      commitment to intra-community solidarity and a desire by many for authentic
      befriending relationships that mirrored understandings of relationships within
      the traditional community. Identifying and alleviating social isolation and
      loneliness imply a set of normative values about community and the optimal social
      relationships within community. This paper proposes that there is a need to
      consider the role played by understandings of community in shaping context
      sensitive interventions to counter social isolation and loneliness in later life.

PMID- 29582502
TI  - The role of the right temporo-parietal junction in social decision-making.
AB  - Identifying someone else's noncooperative intentions can prevent exploitation in
      social interactions. Hence, the inference of another person's mental state might
      be most pronounced in order to improve social decision-making. Here, we tested
      the hypothesis that brain regions associated with Theory of Mind (ToM),
      particularly the right temporo-parietal junction (rTPJ), show higher neural
      responses when interacting with a selfish person and that the rTPJ-activity as
      well as cooperative tendencies will change over time. We used functional magnetic
      resonance imaging (fMRI) and a modified prisoner's dilemma game in which 20
      participants interacted with three fictive playing partners who behaved according
      to stable strategies either competitively, cooperatively or randomly during seven
      interaction blocks. The rTPJ and the posterior-medial prefrontal cortex showed
      higher activity during the interaction with a competitive compared with a
      cooperative playing partner. Only the rTPJ showed a high response during an early
      interaction phase, which preceded participants increase in defective decisions.
      Enhanced functional connectivity between the rTPJ and the left hippocampus
      suggests that social cognition and learning processes co-occur when behavioral
      adaptation seems beneficial.

PMID- 29582503
TI  - Th-17 response and antimicrobial peptide expression are uniformly expressed in
      gastric mucosa of Helicobacter pylori-infected patients independently of their
      clinical outcomes.
AB  - BACKGROUND: The pathological determinism of H. pylori infection is explained by
      complex interplay between bacterial virulence and host inflammatory response. In
      a large prospective multicenter clinical study, Th17 response, expression of
      antimicrobial peptides (AMPs), cagA and vacA status, and bacterial density were
      investigated in the gastric mucosa of H. pylori -infected patients. MATERIALS AND
      METHODS: Gastric inflammatory response was analyzed by RT-qPCR for quantification
      of Th17 cytokines (IL-17A, IL-22), CXCL-8, and AMPs (BD2 and S100A9) mRNA levels
      in gastric biopsies. Detection and genotyping of H. pylori strains were achieved
      by bacterial culture and PCR. RESULTS: Among 787 patients screened for H. pylori,
      269 were analyzed (147 H. pylori -infected and 122 uninfected patients). In H.
      pylori -infected patients, distribution was 83 gastritis, 12 duodenal ulcers, 5
      gastric ulcers, and 47 precancerous and cancerous lesions. CXCL-8, IL-17A, BD2,
      and S100A9 mRNA levels were significantly increased in H. pylori -infected
      patients but, surprisingly, IL-22 was not, and no difference was shown between H.
      pylori -related diseases. A positive correlation was identified between S100A9
      expression and bacterial density. Although expression of the virulence genes cagA
      and vacA did not impact inflammatory response, patients infected with a cagA
      positive strain were associated with severe H. pylori -related diseases.
      CONCLUSION: This study showed that CXCL-8, IL-17A, and AMPs are not differently
      expressed according to the various H. pylori -related diseases. The clinical
      outcome determinism of H. pylori infection is most likely not driven by gastric
      inflammation but rather tends to mainly influenced by bacterial virulence
      factors.

PMID- 29582504
TI  - What do women want? Women want services tailored to their needs.

PMID- 29582505
TI  - Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.
AB  - In vivo morphological study of the human habenula, a pair of small epithalamic
      nuclei adjacent to the dorsomedial thalamus, has recently gained significant
      interest for its role in reward and aversion processing. However, segmenting the
      habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the
      habenula's small size and low anatomical contrast. Although manual and semi
      automated habenula segmentation methods have been reported, the test-retest
      reproducibility of the segmented habenula volume and the consistency of the
      boundaries of habenula segmentation have not been investigated. In this study, we
      evaluated the intra- and inter-site reproducibility of in vivo human habenula
      segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously
      proposed semi-automated myelin contrast-based method and its fully-automated
      version, as well as a previously published manual geometry-based method. The
      habenula segmentation using our semi-automated method showed consistent boundary
      definition (high Dice coefficient, low mean distance, and moderate Hausdorff
      distance) and reproducible volume measurement (low coefficient of variation).
      Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI
      agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic
      resolution) of the same subjects. Overall, our proposed semi-automated habenula
      segmentation showed reliable and reproducible habenula localization, while its
      fully-automated version offers an efficient way for large sample analysis.

PMID- 29582506
TI  - Exploring hydrophobicity limits of polyproline helix with oligomeric
      octahydroindole-2-carboxylic acid.
AB  - The polyproline-II helix is the most extended naturally occurring helical
      structure and is widely present in polar, exposed stretches and "unstructured"
      denatured regions of polypeptides. Can it be hydrophobic? In this study, we
      address this question using oligomeric peptides formed by a hydrophobic proline
      analogue, (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (Oic). Previously, we
      found the molecular principles underlying the structural stability of the
      polyproline-II conformation in these oligomers, whereas the hydrophobicity of the
      peptide constructs remains to be examined. Therefore, we investigated the octan-1
      ol/water partitioning and inclusion in detergent micelles of the oligo-Oic
      peptides. The results showed that the hydrophobicity is remarkably enhanced in
      longer oligomeric sequences, and the oligo-Oic peptides with 3 to 4 residues and
      higher are specific towards hydrophobic environments. This contrasts
      significantly to the parent oligoproline peptides, which were moderately
      hydrophilic. With these findings, we have demonstrated that the polyproline-II
      structure is compatible with nonpolar media, whereas additional manipulations of
      the terminal functionalities feature solubility in extremely nonpolar solvents
      such as hexane.

PMID- 29582507
TI  - The impact of caffeine consumption during 50 hr of extended wakefulness on
      glucose metabolism, self-reported hunger and mood state.
AB  - Caffeine is known for its capacity to mitigate performance decrements. The
      metabolic side-effects are less well understood. This study examined the impact
      of cumulative caffeine doses on glucose metabolism, self-reported hunger and mood
      state during 50 hr of wakefulness. In a double-blind laboratory study,
      participants were assigned to caffeine (n = 9, 6M, age 21.3 +/- 2.1 years; body
      mass index 21.9 +/- 1.6 kg/m2 ) or placebo conditions (n = 8, 4M, age 23.0 +/-
      2.8 years; body mass index 21.8 +/- 1.6 kg/m2 ). Following a baseline sleep
      (22:00 hours-08:00 hours), participants commenced 50 hr of sleep deprivation.
      Meal timing and composition were controlled throughout the study. Caffeine (200
      mg) or placebo gum was chewed for 5 min at 01:00 hours, 03:00 hours, 05:00 hours
      and 07:00 hours during each night of sleep deprivation. Continual glucose
      monitors captured interstitial glucose 2 hr post-breakfast, at 5-min intervals.
      Hunger and mood state were assessed at 10:00 hours, 16:30 hours, 22:30 hours and
      04:30 hours. Caffeine did not affect glucose area under the curve (p = 0.680);
      however, glucose response to breakfast significantly increased after 2 nights of
      extended wakefulness compared with baseline (p = 0.001). There was a significant
      main effect of day, with increased tiredness (p < 0.001), mental exhaustion (p <
      0.001), irritability (p = 0.002) and stress (p < 0.001) on the second day of
      extended wake compared with day 1. Caffeine attenuated the rise in tiredness (p <
      0.001), mental exhaustion (p = 0.044) and irritability (p = 0.018) on day 1 but
      not day 2. Self-reported hunger was not affected by sleep deprivation or
      caffeine. These data confirm the effectiveness of caffeine in improving
      performance under conditions of sleep deprivation by reducing feelings of
      tiredness, mental exhaustion and irritability without exacerbating glucose
      metabolism and feelings of hunger.

PMID- 29582509
TI  - The contribution of smokefree outdoor areas in achieving New Zealand's Smokefree
      2025 goal.
AB  - ISSUES ADDRESSED: With the adoption of Smokefree 2025, further commitment from
      local government to extend smokefree outdoor area policies is becoming
      increasingly important in the presence of high public support. The aim of this
      study was to identify local government commitment in the Canterbury/West Coast
      (CWC) region to the New Zealand Smokefree 2025 goal through provision of
      smokefree outdoor areas. METHODS: Document analysis of the different stages of
      council long-term plans (LTPs) was undertaken, including 239 draft LTP documents,
      5926 public submissions on these documents and 13 final LTP documents. A
      comparison between the 2015 final document and the 2012 final document was
      undertaken. Following this, semi-structured telephone interviews were undertaken
      with council staff. RESULTS: No council had referred to Smokefree 2025 or
      smokefree community spaces in any 2015 LTP draft document. Each of the CWC
      councils received a number of smokefree-related submissions, with the main theme
      being the extension of current Smokefree Outdoor Area Policy. The final LTP
      documents showed that 5 councils had included a brief statement about Smokefree
      2025. Smokefree issues were mentioned more often in the 2012 LTP compared to the
      2015 LTP. CONCLUSIONS: This research highlights a need for more commitment by
      local government to achieving the Smokefree 2025 goal. So what? There are
      opportunities for health groups to work with councils to try and enhance their
      overall commitment to Smokefree 2025 and promote wellbeing.

PMID- 29582508
TI  - Cell-assembled nanoclusters of MSC-targeting Gd-DOTA-peptide as a T2 contrast
      agent for MRI cell tracking.
AB  - A cyclic peptide CC9 that targets cell membrane of mesenchymal stem cells (MSCs)
      is coupled with Gd-DOTA to yield a Gd-DOTA-CC9 complex as MRI contrast agent. It
      is used to label human MSCs (hMSCs) via electroporation. Electroporation-labeling
      of hMSCs with Gd-DOTA-CC9 induces cell-assembly of Gd-DOTA-CC9 nanoclusters in
      the cytoplasm, significantly promotes cell-labeling efficacy and intracellular
      retention time of the agent. In vitro MRI of labeled hMSCs exhibits significant
      signal reduction under T2 -weighted MRI, which can allow long-term tracking of
      labeled cell transplants in in vivo migration. The labeling strategy is safe in
      cytotoxicity and differentiation potential.

PMID- 29582510
TI  - Mental health disclosure amongst clinical psychologists in training:
      Perfectionism and pragmatism.
AB  - OBJECTIVES: This study investigated the incidence of lived experience of mental
      health problems amongst UK-based trainee clinical psychologists and factors
      associated with anticipated disclosure for trainees both with and without lived
      experience. METHODS: A web-based survey comprising the Multidimensional
      Perfectionism Scale, an adapted version of the Perceived Devaluation and
      Discrimination Scale, and questions about lived experience and anticipated
      likelihood of disclosure. RESULTS: The survey was completed by 348 trainees
      across 19 UK training institutions. Sixty-seven percent reported lived experience
      of a mental health problem. For these trainees, there was no difference in
      anticipated likelihood of disclosing to different recipient types after
      controlling for maladaptive perfectionism. However, across all participants,
      anticipated disclosure was associated with maladaptive perfectionism, temporal
      proximity, anticipated stigma (past), and recipient type. Anticipated stigma
      (present) was not associated with anticipated disclosure. CONCLUSIONS: Results
      support an approach to communicating about mental health disclosure that
      incorporates responsibility, interdependency, and transparency. Suggestions for
      further research are discussed.

PMID- 29582511
TI  - Comparative histochemical analysis of glycoconjugates in the nasal vestibule of
      camel and sheep.
AB  - While Corriedale sheep survive in a wide range of climates, which prevents them
      to specialize for one climatic condition only, dromedary camels strictly adapted
      to desert areas. This demands more adaptive mechanisms to hot, dry conditions in
      camels than in sheep. Being the entrance of the nasal cavity, nasal vestibule is
      subjected to various environmental stressors. A protective way is the lining
      epithelium which is cornified in camel, but not in sheep. Mucus nasal secretions
      also play a key role in the protection of underlyings. Additionally, arterio
      venous anastomosis is present in the lamina propria of the nasal vestibule of
      camel. In the present paper, sugar residues in the nasal vestibule of camel were
      analyzed and compared with those of sheep using 14 types of lectins to explore
      the distribution of glycoconjugates that may help the function of camel nasal
      vestibule in desert environment. In camel, none of the lectins could label the
      basal cells of the vestibular epithelium, although the basal cells reacted with
      six lectins in sheep. In camel, LEL and RCA-120 markedly labeled the luminal
      surface. WGA, DBA, SBA, and VVA produced marked intensities on the luminal
      surface in sheep. The mucous glands reacted with six lectins: WGA, s-WGA, VVA,
      PNA, PHA-E, and PHA-L in camel, while all lectins used except s-WGA and PHA-E
      reacted in the sheep. In summary, great differences are observed in the
      glycoconjugate expression between camel and sheep. This suggests that these
      glycoconjugate are related to camel's tolerance for environmental stressors.

PMID- 29582512
TI  - Common and distinct neural correlates of self-serving and prosocial dishonesty.
AB  - People often anticipate certain benefits when making dishonest decisions. In this
      article, we aim to dissociate the neural-cognitive processes of (1) dishonest
      decisions that focus on overall benefits of being dishonest (regardless of
      whether the benefits are self-serving or prosocial) from (2) those that
      distinguish between self-serving and prosocial benefits. Thirty-one participants
      had the opportunity to maximize their monetary benefits by voluntarily making
      dishonest decisions while undergoing functional magnetic resonance imaging
      (fMRI). In each trial, the monetary benefit of being dishonest was either self
      serving or prosocial. Behaviorally, we found dissociable patterns of dishonest
      decisions: some participants were dishonest for overall benefits, while others
      were primarily dishonest for self-serving (compared with prosocial) benefits.
      When provided an opportunity to be dishonest for either self-serving or prosocial
      benefits, participants with a stronger overall tendency to be dishonest had
      stronger vmPFC activity, as well as stronger functional connectivity between the
      vmPFC and dlPFC. Furthermore, vmPFC activity was associated with decisions to be
      dishonest both when the benefits of being dishonest were self-serving and
      prosocial. Conversely, high self-serving-biased participants had stronger
      striatum activity and stronger functional connectivity between the striatum and
      middle-mPFC when they had a chance to be dishonest for self-serving (compared
      with prosocial) benefits. Altogether, we showed that activity in (and functional
      connectivity between) regions in the valuation (e.g., vmPFC and Str) and
      executive control (e.g., dlPFC and mmPFC) systems play a key role in registering
      the social-related goal of dishonest decisions.

PMID- 29582513
TI  - Pollen morphology of subfamily Caryophylloideae (Caryophyllaceae) and its
      taxonomic significance.
AB  - The Pollen morphology of subfamily Caryophylloideae (Caryophyllaceae) from
      different phytogeographical region of Pakistan has been evaluated. In this
      research, 16 species belong to 6 genera of subfamily Caryophylloideae have been
      studied using light (LM) and scanning electron microscopy (SEM) for both
      qualitative and quantitative characters. Different palyno-morphological features
      were observed including; pollen ornamentation, pore ornamentation, echini
      arrangement, echinidensity, number of pori, size of polar and equatorial
      diameter, P/E ratio, exine thickness, and size of pore were studied. The palyno
      morphological characters of subfamily Caryophylloideae have taxonomically
      significant in identification and delimitation of species. Two pollen types,
      i.e., subspheroidal (15 species) and prolate (one species Vaccaria hispanica)
      were observed. Microechinate-punctate and microechinate-perforate pollen
      ornamentation were examined. Two pollen types of pori, i.e., prominent (5
      species) and sunken (11 species) ornamentation have been reported. Three types of
      echini arrangement have been reported irregular, regular and rather regular,
      while three type of echinidensity (i.e., medium, dense and sparse) were observed.
      Pori numbers were found different in different species range from 5 in Silene
      apetala to 19-35 in Silene vulgaris. Based on different palyno-morphological
      characters, taxonomic key was develop for quick and accurate identification. The
      quantitative data were processed using SPSS software for average, minimum,
      maximum, and standard error.

PMID- 29582514
TI  - Altered gray matter volume and disrupted functional connectivity of dorsolateral
      prefrontal cortex in men with heroin dependence.
AB  - AIM: Chronic heroin use can cause various neuropathological characteristics that
      may compromise brain function. The present study evaluated the alteration of gray
      matter volume (GMV) and its resting-state functional connectivity (rsFC) over the
      dorsolateral prefrontal cortex (DLPFC) among male heroin users. METHODS: Thirty
      heroin-dependent men undergoing methadone maintenance therapy and 30 educational
      level- and age-matched male controls were recruited for this study. To assess
      their GMV and rsFC, the participants were evaluated using spoiled gradient echo
      and gradient-recalled echo planar imaging sequences with a 3-Tesla General
      Electric MR scanner under resting state. RESULTS: The heroin-dependent men showed
      lower GMV over the right DLPFC in comparison with the controls. Further
      evaluation of the rsFC of the right DLPFC revealed a marked decrease in
      interhemispheric DLPFC connectivity among those with heroin dependence under
      control of head movement and GMV of the right DLPFC. CONCLUSION: Although the
      mechanism remains unclear, the present study shows that chronic heroin use is
      associated with alteration of morphology as well as rsFC over the right DLPFC. As
      the DLPFC plays an imperative role in various domains of cognitive function,
      service providers for heroin users should consider the impacts of possible DLPFC
      related cognitive deficits on treatment effectiveness.

PMID- 29582515
TI  - Comparison of changes in the oxygenated hemoglobin level during a 'modified rock
      paper-scissors task' between healthy subjects and patients with schizophrenia.
AB  - AIM: The purpose of this study, using single-event-related near-infrared
      spectroscopy (NIRS), was to examine the psychophysiological and social function
      assessment of 30 schizophrenic patients during a modified rock-paper-scissors
      task. METHODS: We set up a screen in front of the subjects, on which pictures of
      hand-gestures for rock, paper, and scissors were randomly presented. Subjects
      were asked to give verbal answers under the conditions of win, lose, and draw,
      respectively. Using the 44-channel NIRS system, we evaluated the maximum
      amplitude of oxygenated hemoglobin, latency, and the area based on the arithmetic
      mean of resulting values after the task between 30 outpatients with schizophrenia
      and 30 healthy subjects, and analyzed the frontal pole area, dorsolateral
      prefrontal region, and parietal association area as regions of interest (ROI).
      RESULTS: In schizophrenic patients, oxygenated hemoglobin changes (Deltaoxy-Hb)
      when losing the task showed a significantly lower level of Deltaoxy-Hb in ROI
      than controls. In addition, a significant positive correlation was observed
      between the Global Assessment of Functioning Scale and Deltaoxy-Hb in ROI, and a
      significant negative correlation was observed between the Negative Syndrome scale
      of the Positive and Negative Syndrome Scale and Deltaoxy-Hb in ROI. CONCLUSION:
      From these results, we conclude that Deltaoxy-Hb levels when performing the
      modified rock-paper-scissors task assessed using NIRS may be a useful
      psychophysiological marker to evaluate the cognitive and social functions of
      schizophrenic patients.

PMID- 29582516
TI  - Long-term tolerability, immunogenicity and efficacy of Nuwiq(r) (human-cl
      rhFVIII) in children with severe haemophilia A.
AB  - INTRODUCTION: Nuwiq(r) (human-cl rhFVIII, simoctocog alfa) is a 4th generation
      recombinant human FVIII, without chemical modification or fusion with any other
      protein, produced in a human cell line. AIM/METHODS: This study (GENA-13) was an
      extension of the GENA-03 study in which previously treated children aged 2-12
      years with severe haemophilia A received Nuwiq(r) prophylaxis for >=6 months.
      GENA-13 examined long-term tolerability, immunogenicity and efficacy of Nuwiq(r)
      prophylaxis in children. RESULTS: Of 59 patients enrolled in GENA-03, 49
      continued Nuwiq(r) prophylaxis in GENA-13 for a median (range) of 30.0 (9.5-52.0)
      months. No patient withdrew due to drug-related adverse events or developed
      inhibitors. Only 2 of 20 518 infusions were associated with possibly related
      adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR)
      was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for
      all bleeds. Younger children (2-5 years) had lower ABRs than children aged 6-12
      years. Annualized bleeding rates were reduced in GENA-13 vs GENA-03, especially
      for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95%
      CI: 0.11, 0.74]). Nuwiq(r) efficacy was rated as excellent/good in the treatment
      of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq(r)
      was rated as excellent for all 17 assessed procedures. CONCLUSION: Long-term
      treatment with Nuwiq(r) for the prevention of bleeds in children with severe
      haemophilia A was well tolerated, effective and reduced spontaneous bleeding by
      up to 70% compared with GENA-03.

PMID- 29582517
TI  - Effects of early motivational interviewing on post-stroke depressive symptoms: A
      pilot randomized study of the Good Mood Intervention program.
AB  - AIMS: The aim of this pilot randomized study was to investigate the feasibility
      of early motivational interviewing, for reducing mood after acute stroke.
      BACKGROUND: Depression is a frequent consequence of stroke that can adversely
      affect recovery. METHODS: DESIGN: Pilot randomized study. Intervention group
      patients received 3, individual motivational interviewing sessions by nurses or
      social workers prior to hospital discharge. PARTICIPANTS: Adult patients with
      acute stroke during 2013 to 2014. BLINDING: Research assistant who collected data
      was blind to group assignment. OUTCOMES: Data were collected at 3 time points:
      baseline, 1-month, and 3-month follow-up. Outcome measures (anxiety, depression,
      quality of life) were analysed by descriptive statistics. RESULTS: Forty-eight
      patients were enrolled, and 79% retention was achieved at 3 months. Eight
      participants withdrew (16.7%), and 2 were unable to participate (death: 2.1% and
      new onset aphasia: 2.1%), leaving 38 participants in the final cohort
      (Intervention: N = 18, Control: N = 20). Anxiety, depression, and quality of life
      measures did not alter significantly in the study period. CONCLUSIONS: Carefully
      designed studies are required to investigate the effectiveness of early
      motivational interviewing for improving mood after stroke. The therapy can be
      administered by nurses, but significant resources are required in terms of
      training and fidelity.

PMID- 29582518
TI  - Long-term safety and effectiveness of brexpiprazole in Japanese patients with
      schizophrenia: A 52-week, open-label study.
AB  - AIM: This study assessed the long-term safety, tolerability, and maintenance of
      the therapeutic effect of brexpiprazole in Japanese patients with schizophrenia.
      METHODS: This 52-week, open-label, flexible-dose (1-4 mg/day) study included
      patients with schizophrenia who continued treatment from a short-term randomized
      placebo-controlled fixed-dose (1, 2, or 4 mg/day) trial and de novo patients who
      switched from other antipsychotics. RESULTS: A total of 282 patients (184 de novo
      and 98 rolled over from short-term trial) entered the 52-week treatment with
      brexpiprazole, and 150 (53.2%) patients completed the week-52 assessment.
      Treatment-emergent adverse events (TEAE) were experienced by 235/281 patients
      (83.6%), and TEAE reported by >=10% of all patients were nasopharyngitis (23.1%)
      and worsening of schizophrenia (22.4%). During the study, most of the TEAE were
      mild or moderate in severity, and there were no deaths, and no clinically
      meaningful mean changes in laboratory values, vital signs, or electrocardiogram
      parameters. Mean scores for the Positive and Negative Syndrome Scale total and
      Clinical Global Impression-Severity remained stable until week 52. CONCLUSION:
      Brexpiprazole was generally safe and well tolerated and maintained therapeutic
      effects in the long-term treatment of Japanese patients with schizophrenia.

PMID- 29582519
TI  - Peripheral neuropathy in Tangier disease: A literature review and assessment.
AB  - Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic
      neuropathies characterized by marked deficiency of high-density lipoproteins and
      accumulation of cholesterol esters in various tissue resulting from reverse
      cholesterol transport deficiency. We report a case of a patient with TD with
      multifocal demyelinating neuropathy with conduction block who presents with
      winging scapula, tongue, and asymmetric extremity weakness. We also present a
      review of all studies published from 1960 to 2017 regarding peripheral neuropathy
      in TD. Our search identified 54 patients with TD with peripheral neuropathy.
      Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal
      sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%),
      and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most
      common (40.7%) clinical manifestation in these patients. The pattern of
      electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more
      predominant in the upper extremities than in the lower extremities and (2)
      slowing of motor nerve conduction was more prominent in the intermediate segment
      than in distal nerve segments. The sural-sparing pattern was present in 34.6% and
      conduction block was present in 11.5% of the patients. Our literature review and
      our case showed the clinical spectrum of TD neuropathy is quite wide and that it
      should be considered in the differential diagnosis of non-uniform demyelinating
      neuropathies.

PMID- 29582520
TI  - Pediatric endocrine society survey of diabetes practices in the United States:
      What is the current state?
AB  - BACKGROUND: The Practice Management Committee (PMC) of the Pediatric Endocrine
      Society (PES) conducted a survey of its membership in February/March, 2016 to
      assess the current state of pediatric diabetes care delivery across multiple
      practice types in the United States. METHODS: The PES distributed an anonymous
      electronic survey (Survey Monkey) via email to its membership and requested that
      only one survey be completed for each practice. RESULTS: Ninety-three unique
      entries from the US were entered into analysis. Care is predominantly delivered
      by multidisciplinary teams, based at academic institutions (65.6%), with >85% of
      the provider types being physicians. Each 1.0 full time equivalent certified
      diabetes educators serves on average 367 diabetic youth. Fee-for-service remains
      the standard method of reimbursement with 57% of practices reporting financial
      loss. Survey respondents identified under-reimbursement as a major barrier to
      improving patient outcomes and lack of behavioral health (BH) providers as a key
      gap in services provided. CONCLUSIONS: Our survey reveals wide variation in all
      aspects of pediatric diabetes care delivery in the United States. Pediatric
      Endocrinologists responding to the survey identified a lack of resources and the
      current fee for service payment model as a major impediment to practice and the
      lack of integrated BH staff as a key gap in service. The respondents strongly
      support its organizations' involvement in the dissemination of standards for care
      delivery and advocacy for a national payment model aligned with chronic diabetes
      care in the context of our emerging value-based healthcare system.

PMID- 29582522
TI  - Education on invasive mechanical ventilation involving intensive care nurses: a
      systematic review.
AB  - BACKGROUND: Intensive care unit nurses are critical for managing mechanical
      ventilation. Continuing education is essential in building and maintaining
      nurses' knowledge and skills, potentially improving patient outcomes. AIMS: The
      aim of this study was to determine whether continuing education programmes on
      invasive mechanical ventilation involving intensive care unit nurses are
      effective in improving patient outcomes. METHODS: Five electronic databases were
      searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing
      and education. Inclusion criteria were invasive mechanical ventilation continuing
      education programmes that involved nurses and measured patient outcomes. Primary
      outcomes were intensive care unit mortality and in-hospital mortality. Secondary
      outcomes included hospital and intensive care unit length of stay, length of
      intubation, failed weaning trials, re-intubation incidence, ventilation
      associated pneumonia rate and lung-protective ventilator strategies. Studies were
      excluded if they excluded nurses, patients were ventilated for less than 24 h,
      the education content focused on protocol implementation or oral care exclusively
      or the outcomes were participant satisfaction. Quality was assessed by two
      reviewers using an education intervention critical appraisal worksheet and a risk
      of bias assessment tool. Data were extracted independently by two reviewers and
      analysed narratively due to heterogeneity. RESULTS: Twelve studies met the
      inclusion criteria for full review: 11 pre- and post-intervention observational
      and 1 quasi-experimental design. Studies reported statistically significant
      reductions in hospital length of stay, length of intubation, ventilator
      associated pneumonia rates, failed weaning trials and improvements in lung
      protective ventilation compliance. Non-statistically significant results were
      reported for in-hospital and intensive care unit mortality, re-intubation and
      intensive care unit length of stay. CONCLUSION: Limited evidence of the
      effectiveness of continuing education programmes on mechanical ventilation
      involving nurses in improving patient outcomes exists. Comprehensive continuing
      education is required. RELEVANCE TO CLINICAL PRACTICE: Well-designed trials are
      required to confirm that comprehensive continuing education involving intensive
      care nurses about mechanical ventilation improves patient outcomes.

PMID- 29582521
TI  - Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs
      in chronic HBV infection.
AB  - The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg)
      and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To
      identify the host genetic factors related to this unusual clinical phenomenon, a
      two-stage study was conducted in the Chinese Han population. In the first stage,
      we performed a case-control (1:1) age- and gender-matched study of 101 cases with
      concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive
      anti-HBs using whole exome sequencing. In the second validation stage, we
      directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48
      cases and 200 controls. Although, in the first stage, a genome-wide association
      study of 58,563 polymorphism variants in 101 cases and 102 controls found no
      significant loci (P-value <= .05/58563), and neither locus achieved a
      conservative genome-wide significance threshold (P-value <= 5e-08), gene-based
      burden analysis showed that OAS3 gene rare variants were associated with the
      coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 <= 0.05/6994). A total of
      16 rare variants were screened out from 21 cases and 3 controls. In the second
      validation stage, one case with a stop-gained rare variant was identified.
      Fisher's exact test of all 149 cases and 302 controls showed that the rare coding
      sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09,
      OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene
      are associated with the coexistence of HBsAg and anti-HBs in patients with
      chronic HBV infection in Chinese Han population.

PMID- 29582523
TI  - UV Resonance Raman Study of Apoptosis, Platinum-Based Drugs, and Human Cell
      Lines.
AB  - As a noninvasive molecular analysis technique, ultraviolet resonance Raman (UVRR)
      spectroscopy represents a label-free method suitable for characterizing
      biomolecules. Using UVRR spectroscopy, we collected spectral fingerprints of UV
      absorbing cellular components, including proteins, nucleic acids, and unsaturated
      lipids. This knowledge was used to guide the assignment of spectra derived from
      intact human cell lines (i. e., HSC-3 and HaCaT) and from the apoptotic events
      induced by cisplatin. Notably, a jet-flow system was employed to generate flowing
      cell suspensions during UVRR measurements, minimizing UV-induced damage. A
      spectral marker is established based on the ratio of Raman intensities at 1488
      and 1655 cm-1 ; this ratio correlates to the level of cell death due to
      apoptosis. Collectively, this work demonstrates that UVRR spectroscopy is a
      sensitive and informative probe of cellular physiology and molecular composition.
      The molecular insight obtained from UVRR measurements can be used to improve
      understanding of therapeutic treatment and to guide drug development and the
      choice of therapeutic agents.

PMID- 29582524
TI  - Selective Activation of a Prodrug by Thioredoxin Reductase Providing a Strategy
      to Target Cancer Cells.
AB  - Elevated reactive oxygen species and antioxidant defense systems have been
      recognized as one of the hallmarks of cancer cells. As a major regulator of the
      cellular redox homeostasis, the selenoprotein thioredoxin reductase (TrxR) is
      increasingly considered as a promising target for anticancer drug development.
      The current approach to inhibit TrxR predominantly relies on the modification of
      the selenocysteine residue in the C-terminal active site of the enzyme, in which
      it is hard to avoid the off-target effects. By conjugating the anticancer drug
      gemcitabine with a 1,2-dithiolane scaffold, an unprecedented prodrug strategy is
      disclosed that achieves a specific release of gemcitabine by TrxR in cells. As
      overexpression of TrxR is frequently found in different types of tumors, the TrxR
      dependent prodrugs are promising for further development as cancer
      chemotherapeutic agents.

PMID- 29582525
TI  - Clinical experience with moroctocog alfa (AF-CC) in younger paediatric patients
      with severe haemophilia A: Two open-label studies.
AB  - INTRODUCTION: The pharmacokinetics (PK), efficacy and safety of moroctocog alfa
      (AF-CC) have been demonstrated in haemophilia A patients aged >=6 years. AIM:
      These studies aimed to further describe moroctocog alfa (AF-CC) experience in
      paediatric patients (<12 years) with severe haemophilia A (FVIII:C < 1%).
      METHODS: Two prospective, open-label studies enrolled patients aged <12 years:
      one study with 37 previously treated patients (PTPs) and another with 23
      previously untreated patients (PUPs). All patients initially received 50 IU/kg of
      moroctocog alfa (AF-CC) to evaluate either recovery alone, or with other PK
      parameters (6 to <12 years) before continuing treatment for 100 exposure days
      (EDs) or 24 months. RESULTS: At baseline, mean (+/-SD) recovery ranged between
      1.32 +/- 0.65 (PUPs aged <2 years) and 2.13 +/- 0.82 (PTPs aged 6 to <12 years).
      The mean (+/-SD) half-life was 9.12 +/- 1.94 hours in PTPs aged 6 to <12 years.
      No new safety signals were detected in either study, 2 transient lower titre
      inhibitors occurred in PTPs while 8 inhibitors (3 low and 5 high titre) were
      detected in PUPs. Most bleeding episodes resolved with one infusion (94%
      [893/954]). The annualised bleeding rate (ABR) in the PTP study was 27.5 and 4.2
      for patients reporting an on-demand and routine prophylaxis regimen at baseline,
      respectively. In the PUP study, the overall ABR was 5.9. CONCLUSION: Moroctocog
      alfa (AF-CC) had expected PK findings (lower recovery in young children compared
      with older children) along with being safe and efficacious in a population of
      young severe haemophilia A patients.

PMID- 29582526
TI  - Whole-exome sequencing reveals a novel missense mutation in the MARS gene related
      to a rare Charcot-Marie-Tooth neuropathy type 2U.
AB  - Charcot-Marie-Tooth (CMT) is a heterogeneous group of progressive disorders,
      characterized by chronic motor and sensory polyneuropathy. This hereditary
      disorder is related to numerous genes and varying inheritance patterns. Thus,
      many patients do not reach a final genetic diagnosis. We describe a 13-year-old
      girl presenting with progressive bilateral leg weakness and gait instability.
      Extensive laboratory studies and spinal magnetic resonance imaging scan were
      normal. Nerve conduction studies revealed severe lower limb peripheral neuropathy
      with prominent demyelinative component. Following presumptive diagnosis of
      chronic inflammatory demyelinating polyneuropathy, the patient received treatment
      with steroids and intravenous immunoglobulins courses for several months, with no
      apparent improvement. Whole-exome sequencing revealed a novel heterozygous
      c.2209C>T (p.Arg737Trp) mutation in the MARS gene (OMIM 156560). This gene has
      recently been related to CMT type 2U. In-silico prediction programs classified
      this mutation as a probable cause for protein malfunction. Allele frequency data
      reported this variant in 0.003% of representative Caucasian population. Family
      segregation analysis study revealed that the patient had inherited the variant
      from her 60-years old mother, reported as healthy. Neurologic examination of the
      mother demonstrated decreased tendon reflexes, while nerve conduction studies
      were consistent with demyelinative and axonal sensory-motor polyneuropathy. Our
      report highlights the importance of next-generation sequencing approach to
      facilitate the proper molecular diagnosis of highly heterogeneous neurologic
      disorders. Amongst other numerous benefits, this approach might prevent
      unnecessary diagnostic testing and potentially harmful medical treatment.

PMID- 29582527
TI  - Rab11 mediates selective recycling and endocytic trafficking in Trypanosoma
      brucei.
AB  - Trypanosoma brucei possesses a streamlined secretory system that guarantees
      efficient delivery to the cell surface of the critical glycosyl
      phosphatidylinositol (GPI)-anchored virulence factors, variant surface
      glycoprotein (VSG) and transferrin receptor (TfR). Both are thought to be
      constitutively endocytosed and returned to the flagellar pocket via TbRab11+
      recycling endosomes. We use conditional knockdown with established reporters to
      investigate the role of TbRab11 in specific endomembrane trafficking pathways in
      bloodstream trypanosomes. TbRab11 is essential. Ablation has a modest negative
      effect on general endocytosis, but does not affect turnover, steady state levels
      or surface localization of TfR. Nor are biosynthetic delivery to the cell surface
      and recycling of VSG affected. TbRab11 depletion also causes increased shedding
      of VSG into the media by formation of nanotubes and extracellular vesicles. In
      contrast to GPI-anchored cargo, TbRab11 depletion reduces recycling of the
      transmembrane invariant surface protein, ISG65, leading to increased lysosomal
      turnover. Thus, TbRab11 plays a critical role in recycling of transmembrane, but
      not GPI-anchored surface proteins. We proposed a two-step model for VSG turnover
      involving release of VSG-containing vesicles followed by GPI hydrolysis.
      Collectively, our results indicate a critical role of TbRab11 in the homeostatic
      maintenance of the secretory/endocytic system of bloodstream T. brucei.

PMID- 29582529
TI  - How can "Super Corals" facilitate global coral reef survival under rapid
      environmental and climatic change?
AB  - Coral reefs are in a state of rapid global decline via environmental and climate
      change, and efforts have intensified to identify or engineer coral populations
      with increased resilience. Concurrent with these efforts has been increasing use
      of the popularized term "Super Coral" in both popular media and scientific
      literature without a unifying definition. However, how this subjective term is
      currently applied has the potential to mislead inference over factors
      contributing to coral survivorship, and the future trajectory of coral reef form
      and functioning. Here, we discuss that the information required to support a
      single definition does not exist, and in fact may never be appropriate, i.e. "How
      Super is Super"? Instead, we advocate caution of this term, and suggest a
      workflow that enables contextualization and clarification of superiority to
      ensure that inferred or asserted survivorship is appropriate into future reef
      projections. This is crucial to robustly unlock how "Super Corals" can be
      integrated into the suite of management options required to facilitate coral
      survival under rapid environmental and climate change.

PMID- 29582528
TI  - Efficient cell delivery mediated by lipid-specific endosomal escape of
      supercharged branched peptides.
AB  - Various densely charged polycationic species, whether of biological or synthetic
      origin, can penetrate human cells, albeit with variable efficiencies. The
      molecular underpinnings involved in such transport remain unclear. Herein, we
      assemble 1, 2 or 3 copies of the HIV peptide TAT on a synthetic scaffold to
      generate branched cell-permeable prototypes with increasing charge density. We
      establish that increasing TAT copies dramatically increases the cell penetration
      efficiency of the peptides while simultaneously enabling the efficient cytosolic
      delivery of macromolecular cargos. Cellular entry involves the leaky fusion of
      late endosomal membranes enriched with the anionic lipid BMP. Derivatives with
      multiple TAT branches induce the leakage of BMP-containing lipid bilayers,
      liposomal flocculation, fusion and an increase in lamellarity. In contrast, while
      the monomeric counterpart 1TAT binds to the same extent and causes liposomal
      flocculation, 1TAT does not cause leakage, induce fusion or a significant
      increase in lamellarity. Overall, these results indicate that an increase in
      charge density of these branched structures leads to the emergence of lipid
      specific membrane-disrupting and cell-penetrating activities.

PMID- 29582530
TI  - Safety and utility of surveillance biopsies in pediatric kidney transplant
      patients.
AB  - There is currently no way to diagnose a rejection before a change in serum
      creatinine. This had led some to start doing SB, but little data exist on the
      utility and safety of SB in pediatric patients. There is also little known on
      practice patterns of pediatric nephrologists. A retrospective review of pediatric
      kidney transplant SB between January 2013 and January 2017 at a single center was
      performed. A survey went to the PedNeph email list. There were 47 SB; 15 at 6
      months, 12 at 1 year, 13 at 2 years, and 7 at 3 years. There were 3 minor (1
      gross hematuria and 2 hematomas) and no major complications. On 6-month SB, 1 had
      SC 1A ACR (6.7%) with no BR ACR. On the 12-month SB, there were 5 with SCBR ACR
      (41.7%) and 1 with SC AMR (8.3%). On the 2-year SB, there were 4 that had SCBR
      ACR (30.8%), and 1 with SC AMR (7.7%). On the 3-year SB, 1 had chronic transplant
      glomerulitis (14.3%). The survey showed that 34.3% of pediatric nephrologists
      perform SB. SB can be performed safely. By early identification of histological
      lesions, SB gives us an opportunity for individualized immunosuppressive regimens
      that may prevent chronic allograft dysfunction and improve long-term graft
      outcome.

PMID- 29582531
TI  - Metabolic control of type 1 diabetes in youth with autism spectrum disorder: A
      multicenter Diabetes-Patienten-Verlaufsdokumentation analysis based on 61 749
      patients up to 20 years of age.
AB  - BACKGROUND: A paucity of reports in the literature exists concerning the co
      existence between autism spectrum disorder (ASD) and type 1 diabetes (T1D).
      OBJECTIVE: To compare clinical characteristics, diabetes management and metabolic
      control in youth with T1D and ASD (T1D-ASD) with youth without ASD (T1D-non ASD).
      METHODS: Using the German/Austrian diabetes patient follow-up registry, this
      study analyzed aggregated data from the last available year of observation for
      each patient with T1D, ages 1-20 with consistent data on insulin regimen and
      glycated hemoglobin (A1C), between January, 2005 and March, 2017. RESULTS: From
      61 749 patients, 150 (0.24%) were identified as T1D-ASD. Non-adjusted comparisons
      showed similar results for mean age at onset and duration of diabetes, but not
      for gender (male: T1D-ASD: 85.3%; T1D-non ASD: 52.8%; P < .001). Unadjusted
      comparisons showed no difference for severe hypoglycemia, diabetic ketoacidosis,
      insulin doses, insulin pump therapy, and body mass index. A statistical
      difference was observed for A1C (P-value .01) and in the number of blood glucose
      (SMBG) tests/day (median [interquartile range]: T1D-ASD 6.0 [4.4-7.0]; T1D-non
      ASD 5.0 [4.4-7.0]; P-value < .001). After adjusting for age, gender, duration of
      diabetes, and year of observation, only SMBG remained significant (P-value .003).
      T1D-ASD used psycho-stimulants (15.3% vs 2.2%; P-value < .001), antipsychotics
      (10.7% vs 0.6%; P-value < .001), and antidepressive medications (3.6% vs 0.7%; P
      value < .001) more frequently. CONCLUSION: Metabolic control was similar in the
      T1D-ASD group compared to T1D-non ASD despite their comorbidity. Awareness of ASD
      remains important in T1D treatment, as both conditions require long-term multi
      disciplinary medical follow-up for optimal outcomes.

PMID- 29582532
TI  - Extracellular HtrA serine proteases: An emerging new strategy in bacterial
      pathogenesis.
AB  - The HtrA family of chaperones and serine proteases is important for regulating
      stress responses and controlling protein quality in the periplasm of bacteria.
      HtrA is also associated with infectious diseases since inactivation of htrA genes
      results in significantly reduced virulence properties by various bacterial
      pathogens. These virulence features of HtrA can be attributed to reduced fitness
      of the bacteria, higher susceptibility to environmental stress and/or diminished
      secretion of virulence factors. In some Gram-negative and Gram-positive
      pathogens, HtrA itself can be exposed to the extracellular environment promoting
      bacterial colonisation and invasion of host tissues. Most of our knowledge on the
      function of exported HtrAs stems from research on Helicobacter pylori,
      Campylobacter jejuni, Borrelia burgdorferi, Bacillus anthracis, and Chlamydia
      species. Here, we discuss recent progress showing that extracellular HtrAs are
      able to cleave cell-to-cell junction factors including E-cadherin, occludin, and
      claudin-8, as well as extracellular matrix proteins such as fibronectin,
      aggrecan, and proteoglycans, disrupting the epithelial barrier and producing
      substantial host cell damage. We propose that the export of HtrAs is a newly
      discovered strategy, also applied by additional bacterial pathogens.
      Consequently, exported HtrA proteases represent highly attractive targets for
      antibacterial treatment by inhibiting their proteolytic activity or application
      in vaccine development.

PMID- 29582533
TI  - Potentially inappropriate medications with polypharmacy increase the risk of
      falls in older Japanese patients: 1-year prospective cohort study.
AB  - AIM: We aimed to evaluate whether potentially inappropriate medications (PIMs)
      increase the risk for adverse clinical outcomes including falls, emergency
      department (ED) visits and unplanned hospitalizations in older Japanese patients
      with chronic diseases, comparing the difference between patients with and without
      polypharmacy. METHODS: A prospective observational cohort study was carried out
      in a Japanese outpatient primary care clinic. Baseline data was collected from
      January to March 2016. A total of 740 patients aged >=65 years with chronic
      diseases were enrolled and were followed up at 1 year; falls, ED visits and
      unplanned hospitalizations were recorded. A questionnaire and review of the
      patients' medical records were used to collect information regarding
      sociodemographic status, comorbidities and medication prescriptions. PIMs were
      defined using the Screening Tool of Older Person's Prescriptions criteria version
      2. Using logistic regression analysis, the incidence of falls, and ED visits and
      hospitalizations were compared between patients with and without PIMs,
      stratifying by number of prescriptions: those with five or more prescriptions and
      those with fewer than five prescriptions. RESULTS: PIMs were identified in 32.3%
      of enrolled patients. After stratification by number of prescriptions, PIMs were
      significantly associated with falls in the group with polypharmacy (OR 2.03, 95%
      CI 1.11-3.69). This association was not seen in the group without polypharmacy.
      PIMs were not associated with ED visits or hospitalizations at the 1-year follow
      up upon multivariate analysis. CONCLUSIONS: The combination of PIMs and
      polypharmacy might increase the risk of falls, therefore clinicians need to pay
      attention to both PIMs and polypharmacy. Geriatr Gerontol Int 2018; 18: 1064
      1070.

PMID- 29582534
TI  - Impact of frailty on chronic pain, activities of daily living and physical
      activity in community-dwelling older adults: A cross-sectional study.
AB  - AIM: The present cross-sectional study investigated the relationship between
      frailty and chronic pain, activities of daily living (ADL), and physical activity
      in community-dwelling older adults. METHODS: Participants were 379 older adults
      who attended community-based exercise classes. Outcome measures were frailty as
      determined by the Kihon Checklist, full pain assessment (including the sensory,
      emotional and cognitive aspects of pain), ADL and physical activity. These
      outcomes were evaluated using validated tests and instruments. Assessments were
      carried out before beginning the exercise classes. Outcome measures were compared
      for participants with and without frailty. Frailty was defined as a total Kihon
      Checklist score >=7, and chronic pain as the presence of related symptoms within
      the past month that had continued for at least 6 months and corresponded with a
      numerical rating scale score of at >=5 at the site of maximum pain. RESULTS: In
      total, 134 (35.4%) participants met the frailty criteria; 60.4% of this group had
      chronic pain. The frail group had significantly worse scores for the sensory,
      emotional and cognitive aspects of pain, ADL and physical activity than the non
      frail group (P < 0.05). Logistic regression analysis adjusted for age and sex
      showed the sensory and emotional aspects of pain were associated with frailty.
      CONCLUSIONS: For community-dwelling older adults with frailty, chronic pain can
      negatively influence sensory, emotional and cognitive aspects of pain, leading to
      a decline in ADL and lower physical activity. Full pain assessment focused on
      sensory and emotional aspects of pain is important to identify frailty among
      older adults. Geriatr Gerontol Int 2018; 18: 1079-1084.

PMID- 29582535
TI  - Nucleocytoplasmic shuttling of the West Nile virus RNA-dependent RNA polymerase
      NS5 is critical to infection.
AB  - West Nile virus (WNV) is a single-stranded, positive sense RNA virus of the
      family Flaviviridae and is a significant pathogen of global medical importance.
      Flavivirus replication is known to be exclusively cytoplasmic, but we show here
      for the first time that access to the nucleus of the WNV strain Kunjin (WNVKUN )
      RNA-dependent RNA polymerase (protein NS5) is central to WNVKUN virus production.
      We show that treatment of cells with the specific nuclear export inhibitor
      leptomycin B (LMB) results in increased NS5 nuclear accumulation in WNVKUN 
      infected cells and NS5-transfected cells, indicative of nucleocytoplasmic
      shuttling under normal conditions. We used site-directed mutagenesis to identify
      the nuclear localisation sequence (NLS) responsible for WNVKUN NS5 nuclear
      targeting, observing that mutation of this NLS resulted in exclusively
      cytoplasmic accumulation of NS5 even in the presence of leptomycin B.
      Introduction of NS5 NLS mutations into FLSDX, an infectious clone of WNVKUN ,
      resulted in lethality, suggesting that the ability of NS5 to traffic into the
      nucleus in integral to WNVKUN replication. This study thus shows for the first
      time that NLS-dependent trafficking into the nucleus during infection of WNVKUN
      NS5 is critical for viral replication. Excitingly, specific inhibitors of NS5
      nuclear import reduce WNVKUN virus production, proving the principle that
      inhibition of WNVKUN NS5 nuclear import is a viable therapeutic avenue for
      antiviral drug development in the future.

PMID- 29582536
TI  - Comparison of body composition and physical and cognitive function between older
      Japanese adults with no diabetes, prediabetes and diabetes: A cross-sectional
      study in community-dwelling Japanese older people.
AB  - AIM: Diabetes is associated with not only cardiovascular and cerebrovascular
      disease, but also reductions in physical and cognitive function. The purpose of
      the present study was to determine whether muscle strength, walking ability and
      balance declined in Japanese community-dwelling older adults with diabetes or
      prediabetes. METHODS: We analyzed data from comprehensive health checkups carried
      out for 1689 individuals (710 men, 979 women; mean age 71.4 +/- 5.6 years)
      between 2011 and 2016. Participants were divided into three groups: no diabetes
      (non-history of diabetes and glycated hemoglobin level <5.7%), prediabetes (non
      history of diabetes, but glycated hemoglobin level was 5.7-6.4%) and diabetes
      (history of diabetes or glycated hemoglobin level >6.4%). Physical and cognitive
      function were compared between groups after adjusting for covariates. RESULTS:
      Participants with diabetes showed higher levels of obesity, comorbidity,
      gonarthrosis, and body fat, and lower levels of physical function relative to
      those observed in participants with prediabetes or no diabetes. After adjusting
      covariates, participants with diabetes showed significantly lower grip strength
      (P < 0.010), slower walking speed (P < 0.005), longer Timed Up and Go test time
      (P < 0.007) and less time spent standing on one foot (P < 0.001) relative to
      those with no diabetes, but not those with prediabetes. CONCLUSIONS: Significant
      functional decline was observed in community-dwelling older adults with diabetes,
      but not in those with prediabetes. Prevention of the progression of prediabetes
      to diabetes is important in avoiding reductions in physical function. Geriatr
      Gerontol Int 2018; 18: 1031-1037.

PMID- 29582537
TI  - Prognostic value of tumour regression grade in locally advanced rectal cancer: a
      systematic review and meta-analysis.
AB  - AIM: The current standard of care for locally advanced rectal cancer involves
      neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There
      is a spectrum of response to neoadjuvant therapy; however, the prognostic value
      of tumour regression grade (TRG) in predicting disease-free survival (DFS) or
      overall survival (OS) is inconsistent in the literature. METHOD: This study was
      performed in accordance with the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using
      Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III
      locally advanced rectal cancer treated with long-course CRT followed by radical
      surgery. The aim of the meta-analysis was to assess the prognostic implication of
      each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was
      assessed. The main outcome measures were DFS and OS. A random effects model was
      performed to pool the hazard ratio (HR) from all included studies. RESULTS: There
      were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological
      complete response (pCR) and 719 (29.9%) with no response. A significant
      association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47,
      P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known
      tumour characteristics, such as ypN, lymphovascular invasion and perineural
      invasion, were also significantly associated with DFS and OS, with estimated
      pooled HRs of 2.2, 1.4 and 2.3, respectively. CONCLUSION: In conclusion, the
      degree of TRG was of prognostic value in predicting long-term outcomes. The
      current challenge is the development of a high-validity tests to predict pCR.

PMID- 29582538
TI  - Mobile phone applications and self-management of diabetes: A systematic review
      with meta-analysis, meta-regression of 21 randomized trials and GRADE.
AB  - We conducted a systematic review with meta-analysis of randomized controlled
      trials that evaluated the effect of diabetes mobile phone applications. A total
      of 1550 participants from 21 studies were included. For type 1 diabetes, a
      significant 0.49% reduction in HbA1c was seen (95% CI, 0.04-0.94; I2  = 84%),
      with unexplained heterogeneity and a low GRADE of evidence. For type 2 diabetes,
      using diabetes apps was associated with a mean reduction of 0.57% (95% CI, 0.32
      0.82; I2  = 77%). The results had severe heterogeneity that was explained by the
      frequency of HCP feedback. In studies with no HCP feedback, low frequency and
      high frequency HCP feedback, the mean reduction is 0.24% (95% CI, 0.02-0.49; I2 
      = 0%), 0.33% (95% CI, 0.07-0.59; I2  = 47%) and 1.12% (95% CI, 0.91-1.32; I2  =
      0%), respectively, with a high GRADE of evidence. There is evidence that diabetes
      apps improve glycaemic control in type 1 diabetes patients. A reduction of 0.57%
      in HbA1c was found in type 2 diabetes patients. However, HCP functionality is
      important to achieve clinical effectiveness. Future studies are needed to explore
      the cost-effectiveness of diabetes apps and the optimal intensity of HCP
      feedback.

PMID- 29582540
TI  - Obituary.

PMID- 29582539
TI  - Association between atherosclerosis and handgrip strength in non-hypertensive
      populations in India and Japan.
AB  - AIM: Although several risk factors contribute to the development of sarcopenia,
      whether preclinical atherosclerosis contributes to the risk of sarcopenia is not
      established. The present cross-sectional study aimed to investigate if there is
      an association between preclinical atherosclerosis and muscle strength among two
      ethnic populations. METHODS: Participants included individuals aged >=40 years
      and enrolled in the third follow-up examination of the Andhra Pradesh Children
      and Parents Study, India, and in the baseline assessments of the Nagasaki Islands
      Study, Japan. Preclinical atherosclerosis was evaluated by carotid intima-media
      thickness, brachial-ankle pulse wave velocity, cardio-ankle vascular index. The
      association of carotid intima-media thickness and pulse wave velocity/cardio
      ankle vascular index with handgrip strength (HGS) was analyzed separately in the
      sexes and for hypertensive status from the two cohorts using a multivariable
      linear regression model. RESULTS: Data on a total of 1501 participants in India
      and 3136 participants in Japan were analyzed. Carotid intima-media thickness was
      negatively associated with HGS in non-hypertensive Indian men (B coefficient = 
      5.38, P = 0.036). Arterial stiffness was also associated with HGS in non
      hypertensive Indian men (B = -0.97, P = 0.001), but not in hypertensive Indian
      men. Same as Indian men, we found the significant associations between arterial
      stiffness and HGS in non-hypertensive women in both India and Japan (B = -0.44, P
      = 0.020, B = -0.63, P = 0.016, respectively), but not in hypertensive women.
      CONCLUSIONS: The negative association between preclinical atherosclerosis and HGS
      was dominantly found in non-hypertensive participants. Geriatr Gerontol Int 2018;
      18: 1071-1078.

PMID- 29582541
TI  - Relationship of muscle cramps to quality of life and sleep disturbance in
      patients with chronic liver diseases: A nationwide study.
AB  - BACKGROUND & AIMS: Although muscle cramps frequently occur in patients with
      cirrhosis, the importance of muscle cramps remains unclear. The aims of this
      study were to investigate the relationship of muscle cramps with quality of life
      (QOL) and sleep disturbance. In addition, this multi-institutional collaborative
      study in Japan investigated factors associated with muscle cramps in patients
      with cirrhosis. METHODS: A total of 1788 patients with chronic liver diseases
      including both non-cirrhosis and cirrhosis completed a questionnaire survey
      investigating: (i) frequency of muscle cramps, (ii) relationship of muscle cramps
      to poor QOL and sleep disturbance, (iii) characteristics of patients who require
      therapeutic intervention and (iv) characteristics of patients prone to
      experiencing muscle cramps. RESULTS: This study revealed that 51.8% of patients
      with cirrhosis have experienced muscle cramps. People who experienced muscle
      cramps were more likely to have reduced QOL and sleep disturbance if muscle
      cramps had (i) high frequency (occurring daily to a few times per week, P < .01);
      (ii) long duration (between a few minutes and a few hours, P < .01) and (iii)
      intense severity (visual analogue scale >=4, P < .01). Age, female sex, positive
      results for hepatitis C virus, low serum albumin concentration, and cirrhosis
      were independent factors related to the severity of muscle cramps. CONCLUSION:
      Muscle cramps occurred with great frequency and were associated with various
      factors such as age, sex, hepatitis C virus and liver function. Many patients
      experience poor QOL (26.3%) due to muscle cramps, and therapeutic interventions
      are therefore needed.

PMID- 29582542
TI  - Observational cohort study of outcomes in patients admitted to the intensive care
      unit for acute exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Patients with acute exacerbation of chronic obstructive pulmonary
      disease (AECOPD) are often referred to the intensive care unit (ICU) for non
      invasive respiratory support. AIMS: To describe the characteristics of patients
      with AECOPD admitted to ICU focusing on the performance of ICU prognostic
      systems, decisions to limit medical therapy and mortality outcomes. METHODS:
      Retrospective review of patients admitted between 2009 and 2016, separately in
      patients with active treatment and limitation or withdrawal of medical therapy.
      ICU acuity scores, blood gas analyses and ICU, in-hospital and 1-year mortality
      were analysed using descriptive statistics and logistic regression. RESULTS: A
      total of 403 patients was studied with an overall ICU mortality of 6.4%. The
      predicted risk of death in hospital using ICU scoring systems was 19% compared to
      the observed mortality of 15%. One-year mortality was 34%. Patients with
      limitation of medical therapy represented 32% of the total cohort and had higher
      mortality in ICU (13%), in hospital (30%) and at 1-year follow up (53%).
      Withdrawal of life-sustaining therapy occurred in 4% of patients who all died in
      ICU. Decreased arterial oxygenation and bicarbonate concentration as well as
      increased arterial carbon dioxide levels were overall associated with an
      increased likelihood of in-hospital mortality but no independent predictors of 1
      year mortality were identified. CONCLUSION: In patients admitted to ICU for
      AECOPD, limitations of medical therapy are frequent and associated with
      significant mortality. Involving palliative care in addition to respiratory
      physicians and intensivists in the management of AECOPD patients admitted to ICU
      needs to be explored further.

PMID- 29582543
TI  - Application of the Nexo method in a general dental practice in the Netherlands: 6
      year results of a RCT.
AB  - OBJECTIVES: The aim of this study was to establish the effect of a non-operative
      caries treatment programme (the Nexo method) in a general dental practice on
      dental caries, oral hygiene and self-reported motivational factors for a 6-year
      period. METHODS: A randomized clinical controlled trial study on caries
      preventive measures in 6- to 12-year-old children was performed among 3 groups of
      children: (i) care as usual (dental check-ups twice a year, accompanied by a
      professional fluoride application and the placement of occlusal sealants on a
      routine basis) (CONTROL); (ii) care as usual plus 2 extra professional fluoride
      applications (IPFA); or (iii) a non-operative caries treatment programme based on
      the Nexo method in which recall interval and caries-preventive measures were
      individualized based on caries activity, eruption stage and motivation of the
      parent (NOCTP). RESULTS: A total of 106 12-year-old children of the initial 230 6
      year-olds completed the full-length study. Children in the NOCTP group developed
      0.67 decayed, missing or filled surfaces (DMFS). This value was 0.86 in the IPFA
      group and 1.02 in control group. The level of oral hygiene was most favourable in
      the NOCTP group (OHI-s score 0.61 vs 0.87 [IPFA] and 0.70 [control]). Differences
      were not statistically significant. CONCLUSION: Children who followed the NOCTP
      programme in this general dental practice did not develop significantly fewer new
      caries lesions compared with children in the IPFA group or the control group
      after 6 years. However, the differences identified after the first 3 years of the
      trial remained apparent.

PMID- 29582544
TI  - Reversibility of platelet P2Y12 inhibition by platelet supplementation: ex vivo
      and in vitro comparisons of prasugrel, clopidogrel and ticagrelor.
AB  - : Essentials Successful outcome of platelet transfusion depends on specific
      antiplatelet therapy in use. We assessed if ticagrelor, clopidogrel or prasugrel
      impacts on donor platelet activity ex vivo. Ticagrelor and/or its active
      metabolite in plasma or bound to platelets can inhibit donor platelets. This
      might compromise the effectiveness of platelet transfusion therapy. SUMMARY:
      Background Platelet transfusion is the conventional approach to restore platelet
      function during acute bleeds or surgery, but successful outcome depends on the
      specific antiplatelet therapy. Notably ticagrelor is associated with inadequate
      recovery of platelet function after platelet transfusion. We examined whether
      plasma and/or platelets from ticagrelor-treated patients influence donor platelet
      function, in comparison with clopidogrel and prasugrel. Methods Platelet
      transfusion was mimicked ex vivo by mixing naive donor platelet-rich plasma (PRP)
      or gel-filtered platelets (GFP) in defined proportions with PRP, plasma or GFP
      from cardiovascular patients receiving standard care including medication with
      prasugrel, clopidogrel or ticagrelor (n = 20 each). Blood was taken 4 h after the
      previous dose. HLA2/HLA28 haplotyping let us distinguish net (all platelet) and
      individual patient/donor platelet reactivity in mixtures of patient/donor
      platelets, measured by flow cytometry analysis of ADP-induced fibrinogen binding
      and CD62P expression. Results ADP responsiveness of donor platelets was
      dramatically reduced by even low (10%) concentrations of PRP or plasma from
      ticagrelor-treated patients. Clopidogrel and prasugrel were associated with more
      modest donor platelet inhibition. GFP from ticagrelor-treated patients but not
      patients receiving clopidogrel or prasugrel also suppressed donor GFP function
      upon mixing, suggesting the transfer of ticagrelor from patient platelets to
      donor platelets. This transfer did not lead to recovery of ADP responsiveness of
      patient's platelets. Conclusion Collectively, these observations support the
      concept that ticagrelor and/or its active metabolite in plasma or bound to
      platelets can inhibit donor platelets, which might compromise the effectiveness
      of platelet transfusion therapy.

PMID- 29582545
TI  - Viscoelastic properties of the posterior eye of normal subjects, patients with
      age-related macular degeneration, and pigs.
AB  - The purpose of this study is to measure, characterize, and compare the
      viscoelastic properties of the posterior eye of advanced dry age-related macular
      degeneration (AMD) patients, age-matched normal subjects, and pigs (3 groups).
      Ten horizontal and ten vertical strips of the macula retina and the underneath
      choroid and sclera were obtained for each group, respectively. They were examined
      by incremental stress-relaxation cycles in body-temperature saline. Mechanical
      response was characterized by the quasi-linear viscoelastic model. All the
      tissues were shown to be nonlinear viscoelastic. Stiffening and isotropization,
      increased relaxation, and softening and isotropization were found in AMD retina,
      choroid, and sclera, respectively, which are the mechanical features of the
      atherosclerotic process. The patients' medical records were in accordance with
      epidemiological studies indicating a relationship between the advanced AMD and
      atherosclerotic vascular disease (ASVD). Moreover, many differences were found
      between the viscoelastic properties of porcine and normal human retina, choroid,
      and sclera. The results suggest that AMD is associated with ASVD through a
      mechanism involving abnormal retinal, choroidal, and scleral mechanics similar to
      those seen in the atherosclerotic process. Moreover, researchers should be aware
      of mechanical differences when using porcine posterior eyes as a substitute for
      human posterior eyes. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 2151-2157, 2018.

PMID- 29582546
TI  - The malaria parasite Plasmodium falciparum Sortilin is essential for merozoite
      formation and apical complex biogenesis.
AB  - The inner membrane complex and the apical secretory organelles are defining
      features of apicomplexan parasites. Despite their critical roles, the mechanisms
      behind the biogenesis of these structures in the malaria parasite Plasmodium
      falciparum are still poorly defined. We here show that decreasing expression of
      the P. falciparum homologue of the conserved endolysomal escorter Sortilin-VPS10
      prevents the formation of the inner membrane complex and abrogates the generation
      of new merozoites. Moreover, protein trafficking to the rhoptries, the
      micronemes, and the dense granules is disrupted, which leads to the accumulation
      of apical complex proteins in the endoplasmic reticulum and the parasitophorous
      vacuole. We further show that protein export to the erythrocyte and transport
      through the constitutive secretory pathway are functional. Taken together, our
      results suggest that the malaria parasite P. falciparum Sortilin has potentially
      broader functions than most of its other eukaryotic counterparts.

PMID- 29582547
TI  - A simple, fast, and accurate thermodynamic-based approach for transfer and
      prediction of gas chromatography retention times between columns and instruments
      Part III: Retention time prediction on target column.
AB  - This is the third part of a three-part series of papers. In Part I, we presented
      a method for determining the actual effective geometry of a reference column as
      well as the thermodynamic-based parameters of a set of probe compounds in an in
      house mixture. Part II introduced an approach for estimating the actual effective
      geometry of a target column by collecting retention data of the same mixture of
      probe compounds on the target column and using their thermodynamic parameters,
      acquired on the reference column, as a bridge between both systems. Part III,
      presented here, demonstrates the retention time transfer and prediction from the
      reference column to the target column using experimental data for a separate
      mixture of compounds. To predict the retention time of a new compound, we first
      estimate its thermodynamic-based parameters on the reference column (using
      geometric parameters determined previously). The compound's retention time on a
      second column (of previously determined geometry) is then predicted. The models
      and the associated optimization algorithms were tested using simulated and
      experimental data. The accuracy of predicted retention times shows that the
      proposed approach is simple, fast, and accurate for retention time transfer and
      prediction between gas chromatography columns.

PMID- 29582548
TI  - Haemoglobin A1c variability is a strong, independent predictor of all-cause
      mortality in patients with type 2 diabetes.
AB  - AIMS: To evaluate various measures of haemoglobin (Hb) A1c variability, compared
      with average HbA1c, as independent predictors of mortality. MATERIALS AND
      METHODS: The Renal Insufficiency And Cardiovascular Events Italian multicentre
      study enroled 15 733 patients with type 2 diabetes from 19 diabetes clinics
      during 2006-2008. A total of 3 to 5 HbA1c measures, obtained during the 2-year
      period before enrolment, were available from 9 centres (8290 patients) and were
      used to calculate average HbA1c (HbA1c -MEAN) and HbA1c variability, measured as
      intra-individual standard deviation (HbA1c-SD), SD adjusted for the number of
      HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV), that is,
      the HbA1c-SD to HbA1c-MEAN ratio. Vital status on October 31, 2015 was retrieved
      for 8252 patients (99.5%). RESULTS: The measures of HbA1c variability increased
      according to quartiles of HbA1c-MEAN and vice versa. HbA1c-MEAN and measures of
      HbA1c variability were associated with all-cause mortality; however, the strength
      of association of HbA1c-MEAN was lower than that of HbA1c -SD, HbA1c-CV or HbA1c
      AdjSD, and disappeared after adjusting for confounders and any of the measures of
      HbA1c variability. Mortality increased with quartiles of HbA1c-MEAN, HbA1c -SD,
      HbA1c-CV and HbA1c-AdjSD, but only the association with HbA1c variability
      measures remained after adjustment for confounders and/or each other measure. In
      the fully adjusted model, mortality risk was lower for HbA1c-SD below the median
      and higher for HbA1c-SD above the median, regardless of whether HbA1c-MEAN was
      below or above the median. Conclusions HbA1c variability is a strong, independent
      predictor of all-cause mortality in type 2 diabetes and appears to be even more
      powerful than average HbA1c in predicting mortality.

PMID- 29582549
TI  - Microglial immune response is impaired against the neurotropic fungus
      Lomentospora prolificans.
AB  - Lomentospora (Scedosporium) prolificans is an opportunistic pathogen capable of
      causing invasive infections in immunocompromised patients. The fungus is able to
      disseminate via the bloodstream finally arriving at the central nervous system
      producing neurological symptoms and, in many cases, patient death. In this
      context, microglial cells, which are the resident immune cells in the central
      nervous system, may play an important role in these infections. However, this
      aspect of anti-L. prolificans immunity has been poorly researched to date. Thus,
      the interactions and activity of microglial cells against L. prolificans were
      analysed, and the results show that there was a remarkable impairment in their
      performance regarding phagocytosis, the development of oxidative burst, and in
      the production of pro-inflammatory cytokines, compared with macrophages.
      Interestingly, L. prolificans displays great growth also when challenged with
      immune cells, even when inside them. We also proved that microglial phagocytosis
      of the fungus is highly dependent on mannose receptor and especially on dectin-1.
      Taken together, these data provide evidence for an impaired microglial response
      against L. prolificans and contribute to understanding the pathobiology of its
      neurotropism.

PMID- 29582551
TI  - Bacterial killing by platelets: making sense of (H)IT.

PMID- 29582550
TI  - Consensus opinion on diagnosis and management of thrombotic microangiopathy in
      Australia and New Zealand.
AB  - Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances
      with the potential to cause significant dysfunction of the kidneys, brain,
      gastrointestinal tract and heart. TMA should be considered in all patients with
      thrombocytopenia and anaemia, with an immediate request to the haematology
      laboratory to look for red cell fragments on a blood film. Although TMA of any
      aetiology generally demands prompt treatment, this is especially so in thrombotic
      thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS),
      where organ failure may be precipitous, irreversible and fatal. In all adults,
      urgent, empirical plasma exchange (PE) should be started within 4-8 h of
      presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a
      disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium
      citrate plasma sample should be collected for ADAMTS13 testing prior to any
      plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome
      due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA,
      and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis
      of aHUS should be considered, for which treatment is with the monoclonal
      complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often
      not possible, except in the minority of patients in whom auto-antibodies against
      factor H are identified, genetic testing ultimately reveals a complement-related
      mutation in a significant proportion of aHUS cases. The presence of other TMA
      associated conditions (e.g. infection, pregnancy/postpartum and malignant
      hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

PMID- 29582552
TI  - Efficacy and tolerability of magnesium plus protein for managing hypomagnesemia
      in pediatric kidney transplant patients.
AB  - We sought to investigate whether magnesium oxide bound to soy protein (MGP)
      increases serum magnesium concentrations with less diarrhea compared to commonly
      prescribed magnesium salts. Subjects were switched to MGP at a near-equivalent
      daily elemental magnesium dose. Mean serum magnesium levels were compared. If
      magnesium levels remained <1.7 mg/dL after switching to MGP, subjects were
      enrolled into Part 2 and received a one-time MGP dose adjustment. The MGP daily
      dose was increased by 266 mg. For both parts 1 and 2, subjects recorded the
      number and quality of their stools to assess gastrointestinal (GI) tolerability
      of MGP. Twelve pediatric kidney transplant recipients completed Part 1. Mean
      serum magnesium levels increased from 1.61 (SD 0.1) on standard MG to 1.69 (SD
      0.1); t(11) = 2.6, P = .02 on MGP. Five subjects completed Part 2, and all
      achieved serum magnesium >=1.7 mg/dL (mean 1.75 mg/dL, SD 0.06; t(4) = 2.7, P =
      .06). Subjects reported the same number of, but looser bowel movements with MGP;
      however, individuals did not perceive intolerable GI symptoms with MGP therapy
      and all chose to remain on MGP at the end of the study. At an equivalent mg/kg/d
      dose of elemental magnesium, serum magnesium levels on MGP were significantly
      higher.

PMID- 29582553
TI  - Farming system and wheat cultivar affect infestation of, and parasitism on,
      Cephus cinctus in the Northern Great Plains.
AB  - BACKGROUND: Cephus cinctus infestation causes $350 million in annual losses in
      the Northern Great Plains. We compared infestation and parasitism of C. cinctus
      in spring (including Kamut; Triticum turgidum ssp. turanicum) and winter wheat
      cultivars grown in organic and conventional fields in Montana, USA. In the
      greenhouse, we compared C. cinctus preference and survival in Kamut, Gunnison,
      and Reeder spring wheat cultivars. RESULTS: Stems cut by C. cinctus varied by
      farming system and the seasonality of the wheat crop. No stems of Kamut in
      organic fields were cut by C. cinctus, but 1.5% [+/-0.35% standard error (SE)] of
      stems in conventional spring wheat, 5% (+/-0.70% SE) of stems in organic winter
      wheat, and 20% (+/-0.93% SE) of stems in conventional winter wheat fields were
      cut by C. cinctus. More larvae of C. cinctus were parasitized in organic (27 +/-
      0.03% SE) compared with conventional (5 +/- 0.01% SE) winter wheat fields. Cephus
      cinctus oviposition, survival, and the number of stems cut were lowest in Kamut
      compared with Gunnison and Reeder. CONCLUSION: Cephus cinctus infestation was
      more common in winter wheat than in spring wheat. Organic fields with fewer cut
      stems also supported more parasitoids. Kamut is a genetic resource for developing
      C. cinctus-resistant cultivars. (c) 2018 Society of Chemical Industry.

PMID- 29582554
TI  - Genetic counselors on the frontline of precision health.
AB  - By enabling precise genetic diagnosis and treatment there is great potential for
      inexpensive, accurate, and widely accessible genomic information to transform
      health care and improve the general well-being of virtually every person. To
      maximize this potential, approaches to genetic counseling and the role of genetic
      counselors will need to adapt to fit changing clinical and commercial needs
      worldwide. This will require overcoming multiple challenges including an
      inadequate workforce; development and implementation of alternate models of
      service delivery; integration of new technologies to improve, extend, and expand
      services; and support for equitable education and counseling among all
      populations. Genetic counselors are aptly poised to take on these challenges. The
      result will be better informed patients and families more capable of utilizing
      genetic information appropriately, making autonomous decisions about their care,
      and modifying their approach to disease risk to actively contribute to their
      health. The contributors to this issue of Seminars discuss how key areas of
      genetic counseling need to evolve and how genetic counselors can play a role in
      shaping the future of precision health.

PMID- 29582555
TI  - Coptisine, a natural alkaloid from Coptidis Rhizoma, inhibits plasmodium
      falciparum dihydroorotate dehydrogenase.
AB  - Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a promising drug
      target for antimalarial chemotherapy. In our continuous efforts to develop more
      potent PfDHODH inhibitors, a unique library of active ingredients from
      traditional Chinese medicine (TCM) has been collected and was screened in this
      study. Through the initial screening, we found that coptisine, a natural alkaloid
      from TCM Coptidis Rhizoma, was a novel and potent inhibitor of PfDHODH with an
      IC50 value of 1.83 +/- 0.08 MUm. At the same time, enzyme kinetic analysis using
      Lineweaver-Burk plot indicated that coptisine is an uncompetitive inhibitor for
      PfDHODH. Thermal shift assay and molecular docking simulation research reveal
      that coptisine is capable of binding with PfDHODH. Moreover, coptisine exhibits
      weak inhibition activity against human DHODH, indicating that coptisine is a
      selective inhibitor of PfDHODH. Taken together, our study highlights the
      potential of active ingredients in TCM as valuable resource for discovering novel
      chemical scaffolds for PfDHODH.

PMID- 29582556
TI  - Implementing the access and waiting time standard for early intervention in
      psychosis in the United Kingdom: An evaluation of referrals and post-assessment
      outcomes over the first year of operation.
AB  - AIM: Improving timely access to evidence-based treatment for people aged 14-65
      years experiencing a first episode psychosis (FEP) or an at-risk mental state
      (ARMS) for psychosis is a national priority within the United Kingdom. An early
      intervention in psychosis (EIP) access and waiting time standard has been set
      which has extended the age range and acceptance criteria for services. METHODS:
      This descriptive evaluation reports upon the referrals and access to treatment
      times within an EIP service over the first year of operating in line with the
      access and waiting time standard. Patient pathways and post-assessment status are
      also described. RESULTS: The service received 406 referrals, of which 88% (n =
      357) were assessed. The mean length of time to treatment was 1.5 weeks, with 88%
      being seen within 2 weeks. Of those who engaged in an assessment, 34% (n = 138)
      were identified as ARMS cases and 30% (n = 123) were identified as FEP. Over 35
      year olds accounted for 22% (n = 80) of the total accepted cases. CONCLUSIONS:
      The findings indicate clinical and operational issues, which will need careful
      consideration in the future planning of services. The high number of ARMS cases
      highlights the importance of clear treatment pathways and targeted interventions
      and may suggest a need to commission distinct ARMS services. The number of people
      who met the extended age and service acceptance criteria may suggest a need to
      adapt or redesign clinical services to meet the age-specific needs of over 35
      year olds and those with an ARMS. It is unclear how changes to the remit of EIP
      services will impact upon future clinical outcomes.

PMID- 29582558
TI  - Exploring treatment decision-making in cancer management for rural residents:
      Patient and provider perspectives on a recently established regional radiotherapy
      service.
AB  - AIM: The aim of this study was to examine stakeholders' views of how the
      establishment of the South West Radiation Oncology Service in Bunbury, Western
      Australia, has affected treatment decision-making, and the extent to which
      patients are involved in the decision-making process. METHODS: Semi-structured in
      depth interviews were undertaken with 21 service providers involved in the
      treatment and care of people with cancer, and 17 adults diagnosed with cancer who
      opted to undergo radiotherapy (RT) treatment at the Service. Data were subject to
      thematic analysis using the qualitative data analysis software NVivo 10. RESULTS:
      Patients were overwhelmingly positive about their experiences at the Service,
      praising the quality of the care provided and noting the convenience associated
      with receiving treatment locally. Most patients reported feeling involved in
      decision-making, but tended to rely on and generally adopt advice from medical
      professionals regarding type and location of treatment. Although service
      providers in the region had become more aware of the regional RT service and
      referrals had increased, some patients continued to travel to the metropolitan
      area for treatment. Reasons identified for this included the need for more
      specialized RT treatment and the more extensive range of allied health services
      offered. CONCLUSION: Increased convenience and a lower financial burden are key
      reasons why rural cancer patients prefer treatment at a regional RT service
      rather than travelling to metropolitan centers. These factors highlight the need
      for ongoing improvement in access to local RT services so that disparities in
      cancer outcomes between rural and metropolitan patients are reduced.

PMID- 29582557
TI  - Five-year results of a phase II trial of preoperative 5-fluorouracil, epirubicin,
      cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab
      in HER2-positive patients) for patients with stage II or III breast cancer.
AB  - We aimed to increase pathologic complete response (pCR) in patients with invasive
      breast cancer by adding preoperative capecitabine to docetaxel following 5
      fluorouracil, epirubicin, cyclophosphamide (FEC) (with trastuzumab for patients
      with HER2-positive disease) and to evaluate 5-year disease-free survival (DFS)
      associated with this preoperative regimen. Chemotherapy included four cycles of
      FEC100 (5-fluorouracil 500 mg/m2 , epirubicin 100 mg/m2 , cyclophosphamide 500
      mg/m2 IV on Day 1 every 21 days) followed by 4 21-day cycles of docetaxel (35
      mg/m2  days 1 and 8) concurrently with capecitabine (825 mg/m2 orally twice daily
      for 14 days followed by 7 days off) (wTX). For HER2-positive patients, treatment
      was modified by decreasing epirubicin to 75 mg/m2 and adding trastuzumab (H) in
      standard doses (FEC75-H ->wTX-H). The study objective was to achieve a pCR rate
      in the breast and axillary lymph nodes of 37% in patients with HER2-negative
      breast cancer and of 67% in patients with HER2-positive breast cancer treated
      with preoperative trastuzumab. A total of 186 patients were enrolled on study. In
      an intent-to-treat analysis, the pCR rate was 31% (37/118, 95% CI: 24-40%) in the
      HER2-negative patients, 24% (15/62, 95% CI: 14-37%) in ER-positive/HER2-negative
      patients, 39% (22/56, 95% CI: 27-53%) in the ER-negative/HER2-negative patients,
      and 46% (29/63, 95% CI: 34-48%) in the HER2-positive patients. The pCR rate in
      the 40 trastuzumab-treated patients was 53% (21/40, 95% CI: 38-67%). Grade 3 and
      4 adverse events included neutropenia, leukopenia, diarrhea, and hand-foot skin
      reactions. One trastuzumab-treated patient developed grade 3 cardiotoxicity, and
      4 others experienced grade 1-2 decrements in left ventricular function; all five
      patients' cardiac function returned to their baseline upon completion of
      trastuzumab. At 5 years, disease-free survival was 70% in the HER2-negative
      population (78% in ER-positive/HER2-negative and 62% in the ER-negative/HER2
      negative patients) and 80% in the HER2-positive patients (87% in the trastuzumab
      treated HER2-positive patients). At 5 years, overall survival was 80% in the HER2
      negative population (88% in ER-positive/HER2-negative and 71% in the ER
      negative/HER2-negative patients) and 86% in the HER2-positive patients (94.5% in
      the trastuzumab-treated HER2-positive patients). FEC100 (FEC75 with trastuzumab)
      followed by weekly docetaxel plus capecitabine, with or without trastuzumab is a
      safe, effective preoperative cytotoxic regimen. However, the addition of
      capecitabine to docetaxel following FEC, with or without trastuzumab, did not
      increase pCR rates nor 5-year DFS over the rates that have been reported with
      standard preoperative doxorubicin/cyclophosphamide (AC) followed by paclitaxel,
      with or without trastuzumab. Therefore, the use of capecitabine as part of
      preoperative chemotherapy is not recommended.

PMID- 29582559
TI  - Preclinical pharmacokinetics and biodistribution of subcutaneously administered
      glycoPEGylated recombinant factor VIII (N8-GP) and development of a human
      pharmacokinetic prediction model.
AB  - : Essentials N8-GP is an extended half-life recombinant factor VIII (FVIII) for
      the treatment of hemophilia A. Subcutaneous (SC) FVIII dosing might reduce the
      treatment burden of prophylaxis. SC N8-GP has a favorable PK profile in animal
      models and disappears from skin injection sites. Combined animal (SC) and
      clinical (IV) data suggest that daily SC dosing may provide prophylaxis. SUMMARY:
      Background N8-GP is an extended half-life recombinant factor VIII (FVIII) for the
      treatment of hemophilia A. Subcutaneous administration of FVIII may reduce the
      treatment burden of prophylaxis; however, standard FVIII products have low
      bioavailability after subcutaneous dosing in animals. Objective To evaluate the
      pharmacokinetics, effectiveness and local distribution of subcutaneously
      administered N8-GP in preclinical models and predict the human pharmacokinetic
      (PK) profile. Methods The pharmacokinetics of subcutaneously administered N8-GP
      were evaluated in FVIII knockout (F8-KO) mice and cynomolgus monkeys; a human PK
      prediction model in hemophilia A patients was developed. The hemostatic effect
      was evaluated in a tail vein bleeding model in F8-KO mice. The injection-site
      distribution and absorption of subcutaneously administered N8-GP were assessed in
      F8-KO mice by the use of temporal fluorescence imaging and immunohistochemistry.
      Results Subcutaneously administered N8-GP had a bioavailability, a first-order
      absorption rate and a half-life, respectively, of 24%, 0.094 h-1 and 14 h in F8
      KO mice, and 26%, 0.33 h-1 and 15 h in cynomolgus monkeys. A dose-dependent
      effect of subcutaneously administered N8-GP on blood loss was observed in mice. A
      minimal amount of N8-GP was detected at the injection site 48-72 h after single
      or multiple dose(s) in F8-KO mice. Subcutaneously administered N8-GP was
      localized to the skin around the injection site, with time-dependent
      disappearance from the depot. PK modeling predicted that subcutaneously
      administered N8-GP at a daily dose of 12.5 IU kg-1 will provide FVIII trough
      levels of 2.5-10% in 95% of patients with severe hemophilia A. Conclusions
      Subcutaneously administered N8-GP may provide effective hemophilia A prophylaxis.
      A phase I clinical trial is underway to investigate this possibility.

PMID- 29582560
TI  - Markov Chain Monte Carlo (MCMC) Method for Studying Magnetic Behaviors in
      Trinuclear Cobalt(II) Compound.
AB  - A CoII coordination polymer built from a mixed azide and zwitterionic pyridinium
      ions and its temperature-dependent magnetic properties are described. We used the
      Markov chain Monte Carlo (MCMC) method to fit the data, and found the following
      results: (1) there are strong correlations between the model parameters; (2) the
      data at above 28 K are well fitted by the magnetism model.

PMID- 29582561
TI  - Effects of locally administered rhBMP-2 and bisphosphonate on bone regeneration
      in the rat fibula.
AB  - OBJECTIVE: To evaluate the ability of xenogenic bone and absorbable collagen
      sponge to function as an rhBMP-2 carrier and the osteoinductivity of
      bisphosphonate by comparison with recombinant human bone morphogenetic protein-2
      (rhBMP-2). MATERIALS AND METHODS: Thirty-two Sprague-Dawley male rats were
      divided into four groups. Segmental ostectomy of both fibulae was performed, and
      the defect area was then treated with Rapiderm Pad (absorbable collagen sponge;
      COL_BMP) or CollaOss (xenogenic bone; XENO_BMP) with application of rhBMP-2.
      Alternatively, both fibulae were grafted with xenogenic bone with different
      bisphosphonate concentrations (XENO_Low BP, XENO_High BP). After 4 or 8 weeks,
      animals were sacrificed, and radiographic, histological, histomorphometric, and
      immunohistochemical analyses were performed. RESULTS: Recombinant human bone
      morphogenetic protein-2 promoted bone formation, regardless of the carrier, and
      exhibited continuity between the graft material and defect area. Moreover, the
      results showed that higher concentrations of bisphosphonate were associated with
      greater bone formation than lower concentrations of bisphosphonate. CONCLUSION:
      Absorbable collagen sponges with rhBMP-2 were advantageous in that there was no
      remaining graft material and that the bone was remodeled to resemble the existing
      fibula. The local application of bisphosphonate promoted new bone formation,
      particularly when used at high concentrations. High-concentration bisphosphonate
      induced new bone formation comparable to rhBMP-2 with lesser remaining bone
      material.

PMID- 29582562
TI  - Description, evaluation and scale-up potential of a model for rapid access to
      early intervention for psychosis.
AB  - AIM: This paper aims to describe the entry protocol of the Prevention and Early
      Intervention for Psychosis Program (PEPP)-Montreal, an early intervention program
      for psychosis. The protocol is designed to fulfil a key objective of the early
      intervention movement-reducing delays to accessing high-quality care. The paper
      also aims to describe how this rapid entry protocol can be deployed in other
      services interested in reducing delays in initiating treatment. METHODS: PEPP
      provides rapid, easy access to quality care by placing a single, well-trained
      professional, the intake clinician, at the point of entry. Anyone can refer a
      youth directly and without formalities to the intake clinician who responds
      promptly and sensitively to all help-seeking, whether by a youth, a family
      member, a school counsellor or anyone acting on behalf of a youth in need. To
      promote accessibility, PEPP guarantees an initial assessment within 72 hours;
      maintains relationships with referral sources; and conducts awareness-enhancing
      outreach activities. RESULTS: Since 2003, PEPP has received 1750 referrals, which
      have all been responded to within 72 hours. Families have been involved in the
      intake process in 60% of the cases and hospitalization may have been averted in
      over half of the referrals originating from emergency-room services. Another
      indicator of success is the very low turnover in the intake clinician's position.
      Overall, the PEPP model has succeeded in providing rapid, engaging, easy and
      youth-friendly access to high-quality care. CONCLUSION: The success of this
      protocol at PEPP has inspired the entry protocols at other first-episode
      psychosis services. Its ability to provide rapid, engaging access to high-quality
      services may allow this protocol to become a model for other early intervention
      services for psychosis and other mental illnesses.

PMID- 29582563
TI  - Prognostic role of circulating tumor cells in patients with EGFR-mutated or ALK
      rearranged non-small cell lung cancer.
AB  - BACKGROUND: Circulating tumor cell (CTC) counts at baseline and follow-up are an
      independent prognostic factor in patients receiving standard chemotherapy for non
      small cell lung cancer (NSCLC). This study further explored the role of CTCs in
      EGFR-mutated and ALK-rearranged NSCLC patients administered targeted therapies as
      first-line treatment. METHODS: CTCs were enumerated with a novel high-efficiency
      detection method from the blood of 43 patients with EGFR-mutated or ALK
      rearranged NSCLC at baseline and at disease-progression. Patients were stratified
      into favorable and unfavorable groups with baseline CTC counts of < 8 or >= 8
      CTCs/3.2 mL, respectively. RESULTS: A total of 76.7% of the patients were
      positive for >= 2 CTCs /3.2 ml blood at baseline. The median progression-free
      survival (PFS) and overall survival (OS) rates of the favorable compared to the
      unfavorable group were longer (11.6 vs. 8.5 months, P = 0.004 for PFS; 21.00 vs.
      17.7 months, P = 0.013 for OS). Multivariate analysis demonstrated that baseline
      CTC count was a strong predictor of PFS (hazard ratio 2.835; 95% confidence
      interval 1.240-6.483; P = 0.014) and OS (hazard ratio 3.317; 95% confidence
      interval 1.360-8.092; P = 0.008). CONCLUSION: Baseline CTC count could be a
      predictive biomarker for EGFR-mutated and ALK-rearranged NSCLCs, which allows for
      better guidance and monitoring of patients over the course of molecular targeted
      therapies.

PMID- 29582565
TI  - IKKs and tumor cell plasticity.
AB  - Nuclear factor kappaB (NF-kappaB) transcription factors are the central hubs of
      signaling pathways connecting proinflammatory signals to cell survival,
      proliferation and cytokine production. In cancers, NF-kappaB signaling influences
      many aspects of tumor development, from initiation to metastasis. These functions
      are mediated by tumor-induced plasticity that allows tumor cells to adapt and
      survive in changing conditions within the tumor microenvironment. Tumor cell
      plasticity is shaped by the inflammatory microenvironment in tumors. This review
      focuses on inhibitor of NF-kappaB kinases, the direct upstream elements of NF
      kappaB regulation, specifically on their conventional and non-conventional
      functions in animal models of tumorigenesis from the recent literature.

PMID- 29582566
TI  - Quantitative time domain analysis of lifetime-based Forster resonant energy
      transfer measurements with fluorescent proteins: Static random isotropic
      fluorophore orientation distributions.
AB  - Forster resonant energy transfer (FRET) measurements are widely used to obtain
      information about molecular interactions and conformations through the dependence
      of FRET efficiency on the proximity of donor and acceptor fluorophores.
      Fluorescence lifetime measurements can provide quantitative analysis of FRET
      efficiency and interacting population fraction. Many FRET experiments exploit the
      highly specific labelling of genetically expressed fluorescent proteins,
      applicable in live cells and organisms. Unfortunately, the typical assumption of
      fast randomization of fluorophore orientations in the analysis of fluorescence
      lifetime-based FRET readouts is not valid for fluorescent proteins due to their
      slow rotational mobility compared to their upper state lifetime. Here, previous
      analysis of effectively static isotropic distributions of fluorophore dipoles on
      FRET measurements is incorporated into new software for fitting donor emission
      decay profiles. Calculated FRET parameters, including molar population fractions,
      are compared for the analysis of simulated and experimental FRET data under the
      assumption of static and dynamic fluorophores and the intermediate regimes
      between fully dynamic and static fluorophores, and mixtures within FRET pairs, is
      explored. Finally, a method to correct the artefact resulting from fitting the
      emission from static FRET pairs with isotropic angular distributions to the
      (incorrect) typically assumed dynamic FRET decay model is presented.

PMID- 29582564
TI  - Genetic variants in mRNA untranslated regions.
AB  - Genome Wide Association Studies (GWAS) have mapped thousands of genetic variants
      associated with complex disease risk and regulating quantitative traits, thus
      exploiting an unprecedented high-resolution genetic characterization of the human
      genome. A small fraction (3.7%) of the identified associations is located in
      untranslated regions (UTRs), and the molecular mechanism has been elucidated for
      few of them. Genetic variations at UTRs may modify regulatory elements affecting
      the interaction of the UTRs with proteins and microRNAs. The overall functional
      consequences include modulation of messenger RNA (mRNA) transcription, secondary
      structure, stability, localization, translation, and access to regulators like
      microRNAs (miRNAs) and RNA-binding proteins (RBPs). Alterations of these
      regulatory mechanisms are known to modify molecular pathways and cellular
      processes, potentially leading to disease processes. Here, we analyze some
      examples of genetic risk variants mapping in the UTR regulatory elements. We
      describe a recently identified genetic variant localized in the 3'UTR of the
      TNFSF13B gene, associated with autoimmunity risk and responsible of an increased
      stability and translation of TNFSF13B mRNA. We discuss how the correct use and
      interpretation of public GWAS repositories could lead to a better understanding
      of etiopathogenetic mechanisms and the generation of robust biological hypothesis
      as starting point for further functional studies. This article is categorized
      under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA
      Evolution and Genomics > Computational Analyses of RNA RNA in Disease and
      Development > RNA in Disease.

PMID- 29582568
TI  - Renovating dental education: A public health issue.

PMID- 29582567
TI  - Association of family history and survival in patients with colorectal cancer: a
      pooled analysis of eight epidemiologic studies.
AB  - A family history of colorectal cancer (CRC) in first-degree relatives (FDRs)
      increases the risk of CRC. However, the influence of family history on survival
      among CRC patients remains unclear. We conducted a pooled analysis of survival in
      5010 incident CRC cases. Cox proportional hazards models were used to estimate
      the association of family history with overall survival (OS) and CRC-specific
      survival (CSS). We also assessed the impact of the number of affected FDRs and
      age at CRC diagnosis in the affected FDRs on survival. Among CRC cases, 819 (16%)
      patients reported a family history of CRC. There were 1580 total deaths over a
      median follow-up of 4.6 years, of which 1046 (66%) deaths were due to CRC. Having
      a family history of CRC was not associated with OS [hazard ratio (HR), 1.03; 95%
      confidence interval (CI), 0.89-1.19] or CSS (HR, 1.13; 95% CI, 0.95-1.36)]. There
      were no associations between the number of affected relatives or age at CRC
      diagnosis of the affected relative with survival (all Ptrend  > 0.05). However, a
      family history of CRC did confer worse CSS in patients diagnosed with distal
      colon cancer (HR, 1.45, 95% CI, 1.03-2.04). A family history of CRC was generally
      not associated with survival after CRC diagnosis. However, having a family
      history of CRC was associated with worse CRC prognosis in individuals with distal
      colon cancer, suggesting a possible genetic predisposition with distinct
      pathogenic mechanism that may lead to worse survival in this group.

PMID- 29582570
TI  - Abstracts from the 43rd American Society of Andrology Annual Meeting, 21-24 April
      2018, Portland, Oregon.

PMID- 29582569
TI  - The potential of plant microbiota in reducing postharvest food loss.
AB  - The role of the plant microbiota in plant establishment, growth and health is
      well studied, but the dynamics of postharvest crop microbiota and its role in
      postharvest crop quality are largely unexplored, although food loss is an
      enormous issue worldwide. The microbiota might be especially important during
      crop storage by either preventing or favouring rots, or quality loss due to, for
      example, sprouting, saccharification, water loss or spoilage. We need more
      research on plant-microbe interactions in postharvest crops to be in future able
      to provide microbial solutions for plant production along the whole food chain
      from field to fork.

PMID- 29582571
TI  - Comprehensive assessment of insulin resistance in non-obese Asian Indian and
      Chinese men.
AB  - AIMS/INTRODUCTION: Indian individuals are more insulin resistant (IR) than
      Chinese individuals, even among those with a non-obese body mass index (BMI).
      However, BMI often underestimates body fat in Indian individuals, and it remains
      unclear whether Indians would remain more IR than Chinese individuals when both
      BMI and body fat are equally matched. MATERIALS AND METHODS: Using the
      hyperinsulinemic-euglycemic clamp with stable-isotope infusion, we
      comprehensively assessed IR between 13 non-obese Indian men with 13 Chinese men
      matched for age, BMI and body fat. We further compared the differences in insulin
      metabolic clearance rate (MCR) between the two groups and its relationship with
      various metabolic parameters. The response of lipid and amino acid metabolism to
      insulin stimulation was also evaluated using metabolomic profiling. RESULTS: The
      rates of endogenous glucose production during fasting were similar, and
      endogenous glucose production was completely suppressed during insulin clamp for
      both ethnic groups. Glucose disappearance during insulin clamp was also similar
      between the two groups, even after accounting for differences in insulin
      concentration. Metabolomic profiles of amino acids and various acylcarnitines
      were similar during both fasting and insulin clamp. However, plasma insulin
      during clamp was significantly higher in Indian men, indicating that insulin MCR
      was lower. Insulin MCR correlated significantly with total adiposity and skeletal
      muscle insulin sensitivity. CONCLUSION: When equally matched for body fat, non
      obese Indian men had similar skeletal muscle insulin sensitivity and endogenous
      glucose production to Chinese men. The effects of insulin on lipid and amino acid
      metabolism were also similar. Low insulin MCR is associated with greater
      adiposity and lower skeletal muscle insulin sensitivity.

PMID- 29582572
TI  - Linking Cognitive and Social Aspects of Sound Change Using Agent-Based Modeling.
AB  - The paper defines the core components of an interactive-phonetic (IP) sound
      change model. The starting point for the IP-model is that a phonological category
      is often skewed phonetically in a certain direction by the production and
      perception of speech. A prediction of the model is that sound change is likely to
      come about as a result of perceiving phonetic variants in the direction of the
      skew and at the probabilistic edge of the listener's phonological category. The
      results of agent-based computational simulations applied to the sound change in
      progress, /u/-fronting in Standard Southern British, were consistent with this
      hypothesis. The model was extended to sound changes involving splits and mergers
      by using the interaction between the agents to drive the phonological
      reclassification of perceived speech signals. The simulations showed no evidence
      of any acoustic change when this extended model was applied to Australian English
      data in which /s/ has been shown to retract due to coarticulation in /str/
      clusters. Some agents nevertheless varied in their phonological categorizations
      during interaction between /str/ and /?tr/: This vacillation may represent the
      potential for sound change to occur. The general conclusion is that many types of
      sound change are the outcome of how phonetic distributions are oriented with
      respect to each other, their association to phonological classes, and how these
      types of information vary between speakers that happen to interact with each
      other.

PMID- 29582573
TI  - Regulation of melanocyte stem cell behavior by the niche microenvironment.
AB  - Somatic stem cells are regulated by their niches to maintain tissue homeostasis
      and repair throughout the lifetime of an organism. An excellent example to study
      stem cell/niche interactions is provided by the regeneration of melanocytes
      during the hair cycle and in response to various types of injury. These processes
      are regulated by neighboring stem cells and multiple signaling pathways,
      including WNT/beta-catenin, KITL/KIT, EDNs/EDNRB, TGF-beta/TGF-betaR, alpha
      MSH/MC1R, and Notch signaling. In this review, we highlight recent studies that
      have advanced our understanding of the molecular crosstalk between melanocyte
      stem cells and their neighboring cells, which collectively form the niche
      microenvironment, and we focus on the question of how McSCs/niche interactions
      shape the responses to genotoxic damages and mechanical injury.

PMID- 29582575
TI  - Rheoreversible Metallogels Derived from Coordination Polymers.
AB  - A series of mixed-ligand-based CdII /CoII coordination polymers (CPs) that were
      derived from two bis(pyridyl)-bis(amide) ligands, 4,4'-oxybis(N-(pyridin-3
      yl)benzamide) (LP) and 4,4'-oxybis(N-(pyridin-4-yl)benzamide) (LP1), and a
      variety of dicarboxylates isophthalates, terephthalates, 1,2
      carboxytranscinamates, and 1,3- and 1,4-phenylene dicarboxylates were synthesized
      based on a rationale that they would occlude solvate guests inside their crystal
      lattice, thereby rendering these CPs suitable as metallogelators. The CPs were
      characterized by using single-crystal X-ray diffraction, elemental analysis,
      powder X-ray diffraction (PXRD), FTIR spectroscopy, and thermogravimetric
      analysis (TGA). Structural analyses revealed that the majority of the CPs were
      lattice-occluded molecular solids, which provided us with an opportunity to study
      their gelation behavior. We observed that, out of eight CPs that were tested,
      seven were able to produce metallogels. A thorough study of the rheological
      behavior of the metallogels was performed and CPG1, CPG2, CPG4, and CPG5 were
      found to exhibit rheoreversible behavior, which was further confirmed by
      rheological experiments. Interestingly, ligand LP was found to form an aqueous
      gel, which was exploited to produce silver nanoparticles.

PMID- 29582576
TI  - Experimental versus theoretical log D7.4 , pKa and plasma protein binding values
      for benzodiazepines appearing as new psychoactive substances.
AB  - The misuse of benzodiazepines as new psychoactive substances is an increasing
      problem around the world. Basic physicochemical and pharmacokinetic data is
      required on these substances to interpret and predict their effects upon humans.
      Experimental log D7.4 , pKa and plasma protein binding values were determined for
      11 benzodiazepines that have recently appeared as new psychoactive substances (3
      hydroxyphenazepam, 4'-chlorodiazepam, desalkylflurazepam, deschloroetizolam,
      diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, phenazepam, and
      pyrazolam) and compared with values generated by various software packages (ACD/I
      lab, MarvinSketch, ADMET Predictor and PreADMET). ACD/I-LAB returned the most
      accurate values for log D7.4 and plasma protein binding while ADMET Predictor
      returned the most accurate values for pKa . Large variations in predictive errors
      were observed between compounds. Experimental values are currently preferable and
      desirable as they may aid with the future 'training' of predictive models for
      these new psychoactive substances.

PMID- 29582574
TI  - Japanese Clinical Practice Guideline for Diabetes 2016.

PMID- 29582578
TI  - Metal Nanoparticles for Diagnosis and Therapy of Bacterial Infection.
AB  - Infectious diseases caused by pathogenic bacteria, especially multidrug-resistant
      bacteria, and their global spreading have become serious public health concerns.
      Early diagnosis and effective therapy can efficiently prevent deterioration and
      further spreading of the infections. There is an urgent need for sensitive,
      selective, and facile diagnosis as well as therapeutically potent treatment. The
      emergence of nanotechnology has provided more options for diagnosis and
      treatments of bacterial infections. Metal nanoparticles and metal oxide
      nanoparticles have drawn intense attention owing to their unique optical,
      magnetic, and electrical properties. These versatile metal-based nanoparticles
      have great potential for selective detection of bacteria and/or therapy. This
      review gives an overview of recent efforts on developing various metal-based
      nanoparticles for bacterial detection and infection therapy. It begins with an
      introduction of fundamental concepts and mechanisms in designing diagnostic and
      therapeutic strategies. Representative achievements are selected to illustrate
      the proof-of-concept in vitro and in vivo applications. A brief discussion of
      challenges and perspective outlook in this field is provided at the end of this
      review.

PMID- 29582579
TI  - 3D Interconnected Mesoporous Alumina with Loaded Hemoglobin as a Highly Active
      Electrochemical Biosensor for H2 O2.
AB  - Alumina is one of the most common and stable metal oxides in nature, which has
      been developed as a novel adsorbent in enrichment of biomolecules due to its
      excellent affinity to phosphor or amino groups. In this study, ordered mesoporous
      alumina (OMA) with interconnected mesopores and surface acidic property is
      synthesized through a solvent evaporation induced co-assembly process using
      poly(ethylene oxide)-b-polystyrene (PEO-b-PS) diblock copolymer as a template and
      aluminium acetylacetonate (Al(acac)3 ) as the aluminium source. The pore size
      (12.1-19.7 nm), pore window size (3.5-9.0 nm) and surface acidity (0.092-0.165
      mmol g-1 ) can be precisely adjusted. The highly porous structure endows the OMA
      materials with high hemoglobin (Hb) immobilization capacity (170 mg g-1 ). The
      obtained Hb@OMA composite is used as an electrocatalyst of biosensor for
      convienet and fast detection of hydrogen peroxide (H2 O2 ) with a low H2 O2
      detection limit of 1.7 * 10-8 m and a wide linear range of 2.5 * 10-8 to 5.0 * 10
      5 m. Moreover, the Hb@OMA sensors show a good performance in real time detection
      of H2 O2 released from Homo sapiens bone osteosarcoma, indicating their potential
      application in complex biological processes.

PMID- 29582577
TI  - Marinobufagenin inhibits glioma growth through sodium pump alpha1 subunit and ERK
      signaling-mediated mitochondrial apoptotic pathway.
AB  - Malignant glioma is one of the most challenging central nervous system diseases
      to treat and has high rates of recurrence and mortality. Current therapies often
      fail to control tumor progression or improve patient survival. Marinobufagenin
      (MBG) is an endogenous mammalian cardiotonic steroid involved in sodium pump
      inhibition. Currently, various studies have indicated the potential of MBG in
      cancer treatments; however, the precise mechanisms are poorly understood. The
      functions of MBG were examined using colony formation, migration, cell cycle, and
      apoptosis assays in glioma cells. A mitochondrial membrane potential assay was
      performed to determine the mitochondrial transmembrane potential change, and
      cytochrome c release from mitochondria was assayed by fluorescence microscopy. An
      immunofluorescence assay was performed, and the nuclear translocation of NF
      kappaB in glioma cells was confirmed by confocal microscopy. Western blotting and
      RT-qPCR were used to detect the protein and gene expression levels, respectively.
      In addition, transfection experiment of ATP1A1-siRNA was further carried out to
      confirm the role of sodium pump alpha1 subunit in the anticancer effect of MBG in
      human glioma. The apoptosis-promoting and anti-inflammatory effects of MBG were
      further investigated, and the sodium pump alpha1 subunit and the ERK signaling
      pathway were found to be involved in the anticancer effect of MBG. The in vivo
      anticancer efficacy of MBG was also tested in xenografts in nude mice. Thus,
      therapies targeting the ERK signaling-mediated mitochondrial apoptotic pathways
      regulated by MBG might represent potential treatments for human glioma, and this
      study could accelerate the finding of newer therapeutic approaches for malignant
      glioma treatment.

PMID- 29582580
TI  - Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via
      pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked
      ubiquitination.
AB  - Streptococcus pneumoniae is the most common causative agent of community-acquired
      pneumonia and can penetrate epithelial barriers to enter the bloodstream and
      brain. We investigated intracellular fates of S. pneumoniae and found that the
      pathogen is entrapped by selective autophagy in pneumolysin- and ubiquitin-p62
      LC3 cargo-dependent manners. Importantly, following induction of autophagy, Rab41
      was relocated from the Golgi apparatus to S. pneumoniae-containing autophagic
      vesicles (PcAV), which were only formed in the presence of Rab41-positive intact
      Golgi apparatuses. Moreover, subsequent localization and regulation of K48- and
      K63-linked polyubiquitin chains in and on PcAV were clearly distinguishable from
      each other. Finally, we found that E3 ligase Nedd4-1 was recruited to PcAV and
      played a pivotal role in K63-linked polyubiquitin chain (K63Ub) generation on
      PcAV, promotion of PcAV formation, and elimination of intracellular S.
      pneumoniae. These findings suggest that Nedd4-1-mediated K63Ub deposition on PcAV
      acts as a scaffold for PcAV biogenesis and efficient elimination of host cell
      invaded pneumococci.

PMID- 29582581
TI  - Mentalization-based treatment or psychodynamic treatment programmes for patients
      with borderline personality disorder - the impact of clinical severity.
AB  - OBJECTIVES: Mentalization-based treatment (MBT), originally designed for patients
      with borderline personality disorder (BPD), may be particularly indicated for
      severe conditions. However, there is limited documentation of how increasing
      severity of personality disorder (PD) effect outcomes of highly specialized
      treatments. This study aimed to investigate associations between clinical
      severity and outcomes for patients in MBT as compared to a psychodynamic group
      based treatment programme (PDT). DESIGN: A naturalistic, longitudinal, comparison
      study. METHODS: The sample included 345 patients with BPD (PDTn = 281, MBTn =
      64). The number of diagnosed PDs, PD criteria, and symptom disorders were chosen
      as baseline indicators of clinical severity. Clinical outcomes (global
      functioning, symptom distress, interpersonal problems) were repeatedly assessed
      over three years. Therapists' fidelity to MBT was satisfactory. Linear mixed
      models were the applied statistics. RESULTS: In PDT, greater clinical severity
      was associated with poorer improvement rates. Clinical severity was not
      associated with significant differences in outcomes for patients in MBT.
      Differences in outcomes for patients in MBT and PDT increased significantly with
      higher severity of disorder. CONCLUSIONS: Supporting previous research, this
      study indicates that clinical benefits associated with MBT also apply for BPD
      patients with severe conditions. The results also suggest that increasing
      severity was a challenge in PDT. PRACTITIONER POINTS: MBT may be particularly
      beneficial for severely disordered BPD patients Differences between MBT and PDT
      were less pronounced in moderately disordered BPD patients.

PMID- 29582582
TI  - miRNA-23a/27a attenuates muscle atrophy and renal fibrosis through muscle-kidney
      crosstalk.
AB  - BACKGROUND: The treatment of muscle wasting is accompanied by benefits in other
      organs, possibly resulting from muscle-organ crosstalk. However, how the muscle
      communicates with these organs is less understood. Two microRNAs (miRs), miR-23a
      and miR-27a, are located together in a gene cluster and regulate proteins that
      are involved in the atrophy process. MiR-23a/27a has been shown to reduce muscle
      wasting and act as an anti-fibrotic agent. We hypothesized that intramuscular
      injection of miR-23a/27a would counteract both muscle wasting and renal fibrosis
      lesions in a streptozotocin-induced diabetic model. METHODS: We generated an
      adeno-associated virus (AAV) that overexpresses the miR-23a~27a~24-2 precursor
      RNA and injected it into the tibialis anterior muscle of streptozotocin-induced
      diabetic mice. Muscle cross-section area (immunohistology plus software
      measurement) and muscle function (grip strength) were used to evaluate muscle
      atrophy. Fibrosis-related proteins were measured by western blot to monitor renal
      damage. In some cases, AAV-GFP was used to mimic the miR movement in vivo,
      allowing us to track organ redistribution by using the Xtreme Imaging System.
      RESULTS: The injection of AAV-miR-23a/27a increased the levels of miR-23a and miR
      27a as well as increased phosphorylated Akt, attenuated the levels of FoxO1 and
      PTEN proteins, and reduced the abundance of TRIM63/MuRF1 and FBXO32/atrogin-1 in
      skeletal muscles. It also decreased myostatin mRNA and protein levels as well as
      the levels of phosphorylated pSMAD2/3. Provision of miR-23a/27a attenuates the
      diabetes-induced reduction of muscle cross-sectional area and muscle function.
      Curiously, the serum BUN of diabetic animals was reduced in mice undergoing the
      miR-23a/27a intervention. Renal fibrosis, evaluated by Masson trichromatic
      staining, was also decreased as were kidney levels of phosphorylated SMAD2/3,
      alpha smooth muscle actin, fibronectin, and collagen. In diabetic mice injected
      intramuscularly with AAV-GFP, GFP fluorescence levels in the kidneys showed
      linear correlation with the levels in injected muscle when examined by linear
      regression. Following intramuscular injection of AAV-miR-23a~27a~24-2, the levels
      of miR-23a and miR-27a in serum exosomes and kidney were significantly increased
      compared with samples from control virus-injected mice; however, no viral DNA was
      detected in the kidney. CONCLUSIONS: We conclude that overexpression of miR
      23a/27a in muscle prevents diabetes-induced muscle cachexia and attenuates renal
      fibrosis lesions via muscle-kidney crosstalk. Further, this crosstalk involves
      movement of miR potentially through muscle originated exosomes and serum
      distribution without movement of AAV. These results could provide new approaches
      for developing therapeutic strategies for diabetic nephropathy with muscle
      wasting.

PMID- 29582583
TI  - A Cascade-Targeting Nanocapsule for Enhanced Photothermal Tumor Therapy with Aid
      of Autophagy Inhibition.
AB  - Autophagy is a homeostatic lysosome-dependent metabolic process to eliminate
      damaged or dysfunctional cellular organelles, which is closely associated with
      tumor progression. Indocyanine green (ICG) can convert NIR light energy to
      localized heat for cancer cell and tissue ablation. However, the effect of
      autophagy modulation on ICG-mediated photothermal therapy remains unknown. In
      this study, it is found that primaquine (PQ) suppresses autophagy flux at a late
      stage through the impeding fusion of the autophagosome with the lysosome to form
      an autophagolysosome, leading to cell apoptosis or necrosis. This autophagosome
      lysosome fusion inhibitory effect and the autophagosome accumulation are more
      evident in the photothermal therapy combined with autophagy inhibition. Motivated
      by this notable effect, a cascade-targeting nanocapsule (HCP) is constructed
      using an organic solvent-free strategy to coencapsulate PQ and ICG. By targeting
      the cluster designation 44 molecule and sequentially enhancing the cell
      penetrating peptide-mediated endocytosis, the codelivery of PQ/ICG by HCP
      achieves selective recognition and reinforces the internalization by MCF-7 cells
      to exert a synergistic therapeutic effect on MCF-7 cells both in vitro and in
      vivo. The HCP system for the photothermal and autophagy inhibition combination
      therapy represents a novel strategy for the treatment of breast cancer.

PMID- 29582585
TI  - Low-level laser therapy as an adjunct to connective tissue graft procedure in the
      treatment of gingival recession defects: A systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to systematically evaluate the effectiveness
      of low level laser therapy (LLLT) as an adjunct to connective tissue graft (CTG)
      procedure for the treatment of gingival recession (GR). MATERIALS AND METHODS:
      The addressed PICO question was; "In patients with Miller Class I or II recession
      defects (Population), what is the effect of LLLT as adjunct to CTG (Intervention)
      in comparison to CTG alone (Comparison) on gingival recession depth (Outcome)"
      Electronic databases were searched up to December 2017. Primary outcomes included
      gingival recession depth (GRD), whereas secondary outcomes were width of
      keratinized tissue (WKT) and relative clinical attachment level gain (RCAL). The
      weighted mean differences (WMD) of outcomes and 95% confidence intervals (CI) for
      each variable were calculated using random effect model. RESULTS: Four randomized
      clinical studies were included. Two studies showed significantly greater
      improvements with LLLT whereas, 2 studies showed comparable outcomes between LLLT
      and CTG group. Considering the effects of adjunctive LLLT as compared to CTG, a
      high degree of heterogeneity for GRD (Q value = 9.40, P = .02, I2 =68.11%) and
      WKT ((Q value = 16.04, P = .001, I2 =81.31%) was noticed among both the groups.
      Meta-analysis showed a statistically significant GRD (WMD= -0.61, 95% CI= -1.23
      to 0.004, P = .05) for LLLT + CTG treatment versus CTG alone only. CONCLUSIONS:
      LLLT improves clinical and patient-centered outcomes of CTG procedures for the
      treatment of GR remains debatable. However, due to the small number of included
      studies and high heterogeneity in the laser parameters, precautions must be
      exercised when interpreting the results of the present systematic review.
      CLINICAL SIGNIFICANCE: Gingival recessions in dentistry are of major esthetic
      concern. Minimal gingival recessions can be treated by flap operations, but the
      predictability and stability of the outcomes is debatable. In the present review,
      low level laser therapy (LLLT) adjunct to connective tissue graft (CTG) depicted
      a significant improvement in the predictability and stability of root coverage
      outcomes compared with CTG alone.

PMID- 29582584
TI  - Dysregulation of metabolic-associated pathways in muscle of breast cancer
      patients: preclinical evaluation of interleukin-15 targeting fatigue.
AB  - BACKGROUND: Breast cancer patients report a perception of increased muscle
      fatigue, which can persist following surgery and standardized therapies. In a
      clinical experiment, we tested the hypothesis that pathways regulating skeletal
      muscle fatigue are down-regulated in skeletal muscle of breast cancer patients
      and that different muscle gene expression patterns exist between breast tumour
      subtypes. In a preclinical study, we tested the hypothesis that mammary tumour
      growth in mice induces skeletal muscle fatigue and that overexpression of the
      cytokine interleukin-15 (IL-15) can attenuate mammary tumour-induced muscle
      fatigue. METHODS: Early stage non-metastatic female breast cancer patients (n =
      14) and female non-cancer patients (n = 6) provided a muscle biopsy of the
      pectoralis major muscle during mastectomy, lumpectomy, or breast reconstruction
      surgeries. The breast cancer patients were diagnosed with either luminal (ER+
      /PR+ , n = 6), triple positive (ER+ /PR+ /Her2/neu+ , n = 5), or triple negative
      (ER- /PR- /Her2/neu- , n = 3) breast tumours and were being treated with curative
      intent either with neoadjuvant chemotherapy followed by surgery or surgery
      followed by standard post-operative therapy. Biopsies were used for RNA
      sequencing to compare the skeletal muscle gene expression patterns between breast
      cancer patients and non-cancer patients. The C57BL/6 mouse syngeneic mammary
      tumour cell line, E0771, was used to induce mammary tumours in immunocompetent
      mice, and isometric muscle contractile properties and fatigue properties were
      analysed following 4 weeks of tumour growth. RESULTS: RNA-sequencing and
      subsequent bioinformatics analyses revealed a dysregulation of canonical pathways
      involved in oxidative phosphorylation, mitochondrial dysfunction, peroxisome
      proliferator-activated receptor signalling and activation, and IL-15 signalling
      and production. In a preclinical mouse model of breast cancer, the rate of muscle
      fatigue was greater in mice exposed to mammary tumour growth for 4 weeks, and
      this greater muscle fatigue was attenuated in transgenic mice that overexpressed
      the cytokine IL-15. CONCLUSIONS: Our data identify novel genes and pathways
      dysregulated in the muscles of breast cancer patients with early stage non
      metastatic disease, with particularly aberrant expression among genes that would
      predispose these patients to greater muscle fatigue. Furthermore, we demonstrate
      that IL-15 overexpression can attenuate muscle fatigue associated with mammary
      tumour growth in a preclinical mouse model of breast cancer. Therefore, we
      propose that skeletal muscle fatigue is an inherent consequence of breast tumour
      growth, and this greater fatigue can be targeted therapeutically.

PMID- 29582586
TI  - Huntington's disease: From basic science to therapeutics.

PMID- 29582588
TI  - Altered lactate metabolism in Huntington's disease is dependent on GLUT3
      expression.
AB  - AIMS: Huntington's disease (HD) is a neurodegenerative disorder characterized by
      progressive abnormalities in cognitive function, mental state, and motor control.
      HD is characterized by a failure in brain energy metabolism. It has been proposed
      that monocarboxylates, such as lactate, support brain activity. During neuronal
      synaptic activity, ascorbic acid released from glial cells stimulates lactate and
      inhibits glucose transport. The aim of this study was to evaluate the expression
      and function of monocarboxylate transporters (MCTs) in two HD models. METHODS:
      Using immunofluorescence, qPCR, and Western blot analyses, we explored mRNA and
      protein levels of MCTs in the striatum of R6/2 animals and HdhQ7/111 cells. We
      also evaluated MCT function in HdhQ7/111 cells using radioactive tracers and the
      fluorescent lactate sensor Laconic. RESULTS: We found no significant differences
      in the mRNA or protein levels of neuronal MCTs. Functional analyses revealed that
      neuronal MCT2 had a high catalytic efficiency in HD cells. Ascorbic acid did not
      stimulate lactate uptake in HD cells. Ascorbic acid was also unable to inhibit
      glucose transport in HD cells because they exhibit decreased expression of the
      neuronal glucose transporter GLUT3. CONCLUSION: We demonstrate that stimulation
      of lactate uptake by ascorbic acid is a consequence of inhibiting glucose
      transport. Supporting this, lactate transport stimulation by ascorbic acid in HD
      cells was completely restored by overexpressing GLUT3. Therefore, alterations in
      GLUT3 expression could be responsible for inefficient use of lactate in HD
      neurons, contributing to the metabolic failure observed in HD.

PMID- 29582589
TI  - Nafion/Titanium Dioxide-Coated Lithium Anode for Stable Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries have shown great potential as high energy-storage
      devices. However, the stability of the Li metal anode is still a major concern.
      This is due to the formation of lithium dendrites and severe side reactions with
      polysulfide intermediates. We herein develop an anode protection method by
      coating a Nafion/TiO2 composite layer on the Li anode to solve these problems. In
      this architecture, Nafion suppresses the growth of Li dendrites, protects the Li
      anode, and prevents side reactions between polysulfides and the Li anode.
      Moreover, doped TiO2 further improves the ionic conductivity and mechanical
      properties of the Nafion membrane. Li-S batteries with a Nafion/TiO2 -coated Li
      anode exhibit better cycling stability (776 mA h g-1 after 100 cycles at 0.2 C, 1
      C=1672 mA g-1 ) and higher rate performance (787 mA h g-1 at 2 C) than those with
      a pristine Li anode. This work provides an alternative way to construct stable Li
      anodes for high-performance Li-S batteries.

PMID- 29582590
TI  - Gap analysis of Mycoplasma bovis disease, diagnosis and control: An aid to
      identify future development requirements.
AB  - There is a worldwide problem of disease caused by Mycoplasma (M.) bovis in
      cattle; it has a significant detrimental economic and animal welfare impact on
      cattle rearing. Infection can manifest as a plethora of clinical signs including
      mastitis, pneumonia, arthritis, keratoconjunctivitis, otitis media and genital
      disorders that may result in infertility and abortion. Current diagnosis and
      control information are reviewed and analysed to identify gaps in knowledge of
      the causative organism in respect of the disease pathology, diagnosis and control
      methods. The main considerations are as follows: no vaccines are commercially
      available; antimicrobial resistance is increasing; diagnostic and antimicrobial
      sensitivity testing needs to be improved; and a pen-side test would facilitate
      more rapid diagnosis and implementation of treatment with antimicrobials. More
      data on host susceptibility, stress factors, immune response and infectious dose
      levels are required. The impact of asymptomatic carriers, M. bovis survival in
      the environment and the role of wildlife in transmitting the disease also needs
      investigation. To facilitate development of vaccines, further analysis of more M.
      bovis genomes, its pathogenic mechanisms, including variable surface proteins, is
      required, along with reproducible disease models.

PMID- 29582591
TI  - Glyphosate: The world's most successful herbicide under intense scientific
      scrutiny.

PMID- 29582592
TI  - Simultaneous in vivo confocal reflectance and two-photon retinal ganglion cell
      imaging based on a hollow core fiber platform.
AB  - We have developed a compact hollow core fiber (HCF)-based imaging platform
      capable of simultaneous in vivo confocal reflectance and two-photon imaging
      through the mouse pupil. We demonstrate the performance of this platform by
      imaging retinal ganglion cells (RGCs) in which the fluorophores YFP and GCaMP3
      are expressed in Thy1-YFP-16 and Thy1-GCaMP3 transgenic mice, respectively.
      Confocal reflectance images of the mouse retina served as a reference for the
      simultaneous acquisition of the two-photon signals that clearly showed RGCs with
      single-cell resolution. The use of an HCF platform makes the system compact with
      future application in the longitudinal investigation into the structure and
      function of healthy and diseased RGCs.

PMID- 29582593
TI  - [Preparation of hydrophilic polymer brushes magnetic microspheres by surface
      initiated for magnetic dispersive solid phase extraction of tetracycline
      antibiotic residues from honey].
AB  - Activators regenerated by electron transfer-atom transfer radical polymerization
      (ARGET-ATRP) was applied to the continuous grafting of polybasic polymers and
      poly(ethylene glycol) (PEG) brushes on the surface of the magnetic microspheres
      (MMs). At first, the MMs were coated with silica gel, modified by amino group,
      and then 2-bromoisobutyryl bromide was grafted on the surface of MMs. After that,
      the hydrophilic polymer brushes magnetic microspheres (HMMs) were prepared by
      polymerization on the surface of the MMs. HMMs were characterized by transmission
      electron microscope (TEM) and Fourier transform-infrared (FT-IR) spectrometer.
      The adsorption performance to protein was studied. The results demonstrated that
      HMMs have the relatively uniform particle size, good dispersity and excellent
      protein resistance properties. Tetracycline antibiotics (TCs, tetracycline
      hydrochloride, chlortetracycline hydrochloride and doxycycline hydrochloride) in
      honey samples were determined by magnetic dispersion solid phase extraction
      (MDSPE) using the prepared HMMs and high performance liquid chromatography
      (HPLC). The average recoveries were obtained in the range of 85.8%-94.5%. The
      limits of detection (LODs) and limits of quantification (LOQs) of the proposed
      method were in the ranges of 1.92-2.56 MUg/kg and 6.40-8.53 MUg/kg, respectively.
      The proposed method was successfully applied to fast clean-up and enrichment of
      the TCs residues in honey.

PMID- 29582594
TI  - [Preparation and evaluation of a new type of amino-bonded silica chromatographic
      stationary phase for the determination of lactose].
AB  - A method for the separation and determination of lactose and sucrose using high
      performance liquid chromatography-refractive index (HPLC-RI) detection base on
      the prepared amino-bonded silica gel chromatographic stationary phase was
      established. The method was accorded to the content determination method in
      Pharmacopoeia of the People's Republic of China (2015). Then, a series of
      chromatographic behaviors of lactose and sucrose such as the retention times,
      resolutions and peak area stabilities were investigated on three different types
      of amino-bonded silica columns (300 mm*4.6 mm, 5 MUm). The mobile phase was
      acetonitrile-water (70:30, v/v) with isocratic elution, the flow rate was 1.0
      mL/min and the injection volume was 10 MUL. The resolution of lactose and sucrose
      was 3.03 by isopropyl side chain protected amino column, and the peak shape of
      each target compound was good. The relative standard deviation (RSD) of peak area
      of lactose was 1.14%, less than 2.0% prescribed in the Pharmacopoeia of the
      People's Republic of China (2015). Therefore, this method meets the requirements
      of lactose content determination, and is suitable as the quality control method
      in the above mentioned Pharmacopoeia.

PMID- 29582587
TI  - Disrupted striatal neuron inputs and outputs in Huntington's disease.
AB  - Huntington's disease (HD) is a hereditary progressive neurodegenerative disorder
      caused by a CAG repeat expansion in the gene coding for the protein huntingtin,
      resulting in a pathogenic expansion of the polyglutamine tract in the N-terminus
      of this protein. The HD pathology resulting from the mutation is most prominent
      in the striatal part of the basal ganglia, and progressive differential
      dysfunction and loss of striatal projection neurons and interneurons account for
      the progression of motor deficits seen in this disease. The present review
      summarizes current understanding regarding the progression in striatal neuron
      dysfunction and loss, based on studies both in human HD victims and in genetic
      mouse models of HD. We review evidence on early loss of inputs to striatum from
      cortex and thalamus, which may be the basis of the mild premanifest bradykinesia
      in HD, as well as on the subsequent loss of indirect pathway striatal projection
      neurons and their outputs to the external pallidal segment, which appears to be
      the basis of the chorea seen in early symptomatic HD. Later loss of direct
      pathway striatal projection neurons and their output to the internal pallidal
      segment account for the severe akinesia seen late in HD. Loss of parvalbuminergic
      striatal interneurons may contribute to the late dystonia and rigidity.

PMID- 29582595
TI  - [Preparation of phenyl-modified silica nanoflake fibers and the solid-phase
      microextraction of polycyclic aromatic hydrocarbons].
AB  - A novel silica-based solid-phase microextraction (SPME) fiber was successfully
      fabricated by the immobilization of silica nanoflakes (SiO2NFs) onto the
      hydrothermally treated nickel-titanium alloy (NiTi) wire using sol-gel method,
      followed by self-assembled surface modification of phenyltrichlorosilane. The
      extraction performance of the fabricated fiber was evaluated using typical
      aromatic compounds in direct-immersion mode of SPME. The fiber exhibited the high
      extraction capability and good extraction selectivity for polycyclic aromatic
      hydrocarbons (PAHs) in water samples. The influences of stirring rate, extraction
      temperature, extraction time and ionic strength on the extraction efficiencies
      were optimized coupled to HPLC with UV detection. Under the optimized conditions,
      the five PAHs presented good linearity in the certain mass concentration ranges
      with correlation coefficients (r) greater than 0.999, and LODs ranged from 0.013
      to 0.108 MUg/L. The intra-day and inter-day RSDs were from 4.1% to 5.9% and 4.8%
      to 6.8% for the PAHs at the spiked level of 50 MUg/L with the single fiber,
      respectively. The recoveries of the five PAHs in real water samples spiked at 10
      MUg/L and 30 MUg/L ranged from 90.8% to 105.7% and 93.6% to 103.1%, respectively.
      Moreover, the phenyl-modified SiO2NFs coated NiTi fiber has high stability and
      good preparation reproducibility. The developed method is suitable for the
      concentration and determination of the target PAHs in environmental water
      samples.

PMID- 29582596
TI  - [Two-dimensional liquid chromatography separation and high resolution mass
      spectrometry analysis for proteome of rice leaves based on different extraction
      methods].
AB  - A two-dimensional liquid chromatography (2D LC) system was developed to separate
      proteins from rice leaves, which was extracted by phenol method, followed by the
      analysis with linear trap quadrupole orbitrap mass spectrometry (LTQ/Orbitrap
      MS). After proteins were extracted with phenol method, the enzymolytic peptides
      were separated by offline two-dimensional RP-RP system and detected by
      LTQ/Orbitrap MS, yielding 2712 proteins. Liquid chromatography separation system
      (1D LC and 2D LC) and protein extraction methods (phenol method, sodium dodecyl
      sulfate method (SDS method) and trichloroacetic acid/acetone method (TCA/acetone
      method)) were compared. Proteins identified by 2D LC were 2712, 2415 and 1914
      with the above three extraction methods, respectively. The proteins were 2.7
      fold, 2.5-fold and 1.9-fold the number of proteins identified by 1D LC
      respectively. And in terms of 2D LC, the proteins identified by phenol method
      were 297 and 798 more than SDS method and TCA/acetone method, respectively. Some
      proteins with extreme properties, such as very acidic or basic protein and high
      relative molecular mass proteins, were only identified in phenol method.
      Furthermore, proteins, which were extracted by different extraction methods and
      separated by 2D LC, were classified according to biological functions. It was
      found that protein functions by the three extraction methods were complementary.
      However, phenol method had the most variety of functions. The method provides
      technological support for rice proteomics and reference for research techniques
      of other crop proteomics.

PMID- 29582597
TI  - [Rapid determination of 25 drug residues in aquatic products by ultra performance
      liquid chromatography-quadrupole/electrostatic field orbitrap high resolution
      mass spectrometry].
AB  - An ultra performance liquid chromatography-quadrupole/electrostatic field
      orbitrap high resolution mass spectrometry (UPLC-Q Orbitrap HRMS) method was
      developed for the rapid screening of 25 drug residues in aquatic products by the
      application of a novel enhanced matrix removal of lipids (EMR-Lipid). The samples
      were extracted with acetonitrile, cleaned-up with EMR-Lipid, and salted out with
      3.0 g sodium chloride and 3.0 g sodium sulfate. The separation of the 25 drug
      residues was performed on an ACQUITY UPLC BEH C18 column (100 mm*2.1 mm, 1.7 MUm)
      with gradient elution. Acetonitrile containing 0.1% (v/v) formic acid and 0.1%
      (v/v) formic acid aqueous solution were used as mobile phases. The compounds were
      detected by Full scan/date dependent MS/MS (Full MS/dd-MS2) via heated
      electrospray ionization (HESI) source. The calibration curves were linear with
      correlation coefficients (r) greater than 0.997. The limits of detection (LODs)
      ranged from 0.1 MUg/kg to 1.0 MUg/kg. The average spiked recoveries of the 25
      target compounds were between 70.1% and 108.9% with relative standard derivations
      (RSDs) from 2.1% to 13.8%. Compared with the previous methods, this method has
      characteristics of simpler sample preparation and higher sensitivity.

PMID- 29582598
TI  - [Rapid screening of 24 tranquillizer drugs in fish and fishery products by ultra
      high performance liquid chromatography-quadrupole/electrostatic field orbitrap
      high resolution mass spectroscopy].
AB  - A method was developed for the simultaneous determination of 24 tranquillizer
      drugs in fish and fishery products using ultra-high performance liquid
      chromatography-quadrupole/electrostatic field orbitrap high resolution mass
      spectrometry (UPLC-Q-Orbitrap HRMS). The samples were extracted with
      acetonitrile. Then, the extracts were concentrated, dissolved by 50% (v/v)
      methanol aqueous solution, cleaned up with hexane saturated by acetonitrile. The
      separation was performed on an ACQUITY UPLC(r) BEH C18 column (100 mm*2.1 mm, 1.7
      MUm) with the gradient elution using acetonitrile and water both containing 0.1%
      (v/v) formic acid as mobile phases. The drugs were analyzed by full MS scan/data
      dependent MS2 (Full MS/dd-MS2)(Top 1) mode by heating electrospray ion (HESI)
      source. The results were quantified by external standard method. The calibration
      curves of the 24 tranquillizer drugs were linear in their respective linear
      range, the decision coefficients (r2) were no less than 0.9968. The average
      spiked recoveries of the 24 tranquillizer drugs were 58.9%-122.9%, and the
      relative standard deviations (RSDs) were 0.1%-16.4% in the six kinds of fish and
      fishery products at three spiked levels. The limits of quantification (LOQs) of
      the 24 tranquillizer drugs were 0.1-5.0 MUg/kg. The method is simple, rapid,
      sensitive, reliable and suitable for the screening of the 24 tranquillizer drugs
      in fish and fishery products.

PMID- 29582599
TI  - [Simultaneous determination of seven high risk pesticide residues in royal jelly
      by high performance liquid chromatography-tandem mass spectrometry].
AB  - A method was developed for the simultaneous determination of seven high risk
      pesticides in the royal jelly, eg. tau-fluvalinate, triadimenol, coumaphos,
      haloxyfop, carbendazim, thiophanate-ethyl and thiophanate-methyl by high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). First,
      the royal jelly samples were extracted with acetonitrile under alkaline
      conditions. After dehydration by anhydrous sodium sulfate, the extracts were
      enriched and purified through solid-phase extraction (SPE) with Oasis HLB
      cartridges. Finally, the pesticides were detected by HPLC-MS/MS method. The
      separation was carried out on a Venusil MP C18 column with gradient elution.
      Methanol (containing 0.1% (v/v) formic acid) and 0.5 mmol/L ammonium acetate
      aqueous solution (containing 0.1% (v/v) formic acid) were used as the mobile
      phases. The detection was achieved using electrospray ionization in positive ion
      (ESI+) mode and multiple reaction monitoring (MRM) mode for data collection.
      Quantification was carried out using internal standard method. The results showed
      that the seven high risk pesticides were linear in the range of 5-100 MUg/kg. The
      linear correlation coefficients (r2) were 0.9921-0.9996. The limits of detection
      (LODs) and limits of quantification (LOQs) of the seven high risk pesticides were
      0.5-2.0 MUg/kg and 1.0-5.0 MUg/kg, respectively. The average recoveries at the
      three spiked levels were 80.5%-101.3%, and the relative standard deviations were
      3.6%-9.4% (n=3). This method is simple, effective and sensitive, and is suitable
      for the determination of the pesticide residues in royal jelly.

PMID- 29582600
TI  - [Determination of carbendazim and thiabendazole in wine and beer by ultra high
      performance liquid chromatography-high resolution mass spectrometry coupled with
      dispersive micro solid-phase extraction].
AB  - A rapid method was established for the determination of carbendazim and
      thiabendazole in wine and beer by ultra high performance liquid chromatography-Q
      Orbitrap high resolution mass spectrometry and dispersive micro solid-phase
      extraction (DMSPE) based on a strong cation exchange adsorbent (PCX). For the
      pretreatment method, the amount of PCX, the volume percentage of acetonitrile,
      the volume percentage of ammonium hydroxide and the volume of eluent were
      optimized. The analytes were separated on a BEH C18 column (50 mm*2.1 mm, 1.7
      MUm) and detected using targeted single ion monitoring-data dependent tandem mass
      spectrometry (tSIM-ddMS2) scan mode. The method showed a good linearity within a
      certain concentration ranges with correlation coefficients R2 >= 0.9999. The
      detection limits of carbendazim and thiabendazole in wine and beer were 0.02 and
      0.01 MUg/L, and the quantification limits were 0.06 and 0.03 MUg/L. The average
      recoveries of carbendazim and thiabendazole at the spiked levels of 0.1, 1.0 and
      100 MUg/L were in the ranges of 95.6%-110.2% and 87.5%-102.8%, with intra-day
      precision (RSDr) ranges from 1.8%-5.2% and 1.3%-4.8%, and inter-day precision
      (RSDR) ranges from 4.3%-8.7% and 4.8%-9.4%. The method is rapid, simple and
      sensitive for the simultaneous determination of carbendazim and thiabendazole in
      wine and beer.

PMID- 29582601
TI  - [Determination of sedative and beta-receptor hormone residues in feed by ultra
      high performance liquid chromatography-tandem mass spectrometry].
AB  - An analysis and detection method for eight sedatives and fifteen beta-receptor
      hormones in feed was established by ultra high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS). The sample was extracted with
      acetonitrile-1% (v/v) trichloroacetic acid aqueous solution (7:3, v/v), and
      purified by cationic solid phase extraction column. The extracts were separated
      on an Agilent Zorbax Eclipse Plus C18 chromatographic column (100 mm*3.0 mm, 1.8
      MUm) and then quantified via internal standard method. The results showed that
      the linear relationships of the 23 targets were good in the range of 2.0-200.0
      MUg/L (r2> 0.99). The average recoveries of the targets spiked in the matrix of
      feed samples were within 75.1%-102.4% in three spiked levels of 5.0, 10, 50
      MUg/kg, and the relative standard deviations (RSDs) were within 4.3%-14.3% (n=6).
      This method with high purification efficiency and extensive scope of application
      can be applied to screening and detecting sedatives and beta -receptor hormones
      in feed.

PMID- 29582602
TI  - [Determination of metformin hydrochloride, melamine and dicyandiamide in
      metformin hydrochloride preparations by tandem dual solid phase extraction
      cartridges-high performance liquid chromatography-electrospray ionization multi
      stage mass spectrometry].
AB  - A method for the confirmation and quantification of metformin hydrochloride and
      its relative substances melamine and dicyandiamide using tandem dual solid phase
      extraction (SPE) cartridges and high performance liquid chromatography
      electrospray ionization multi-stage mass spectrometry (HPLC-ESI-MSn) was
      developed. The samples were extracted with anhydrous ethanol containing 0.1%
      (v/v) acetic acid under ultrasound-assisted conditions. The extracts were
      concentrated and purified using Cleanert PCX and C18 tandem dual solid phase
      extraction cartridges, and eluted with 5% (v/v) ammonia methanol solution. The
      separation was performed on a Kromasil-C18 column (100 mm*4.6 mm, 3.5 MUm) with
      gradient elution. The detection was performed in selected ion monitoring (SIM)
      mode using electrospray ionization multi-stage mass spectrometry. The external
      standard method was used for quantification. The extraction solvents, types of
      SPE cartridges and eluents were optimized by comparing the recoveries under
      different conditions. The results showed that the detector response of each
      target compound was linear in corresponding mass concentration ranges with the
      correlation coefficients (r2) >= 0.9992. The limits of detection (LODs) and the
      limits of quantification (LOQs) of the three analytes were 1.48-13.61 MUg/kg and
      5.96-45.67 MUg/kg, respectively. The recoveries of the three analytes were 65.02%
      118.33% spiked at low, medium and high levels. The relative standard deviations
      (RSDs) were no more than 13.41%. The method is reliable, easy, and has a better
      purification effect. The method can be applied to the routine analysis of
      metformin hydrochloride and its relative substances melamine and dicyandiamide in
      different preparations of metformin hydrochloride.

PMID- 29582603
TI  - [Determination of organic acids in the root exudates of Cr-hyperaccumulator
      Leersia hexandra Swartz using high performance liquid chromatography].
AB  - High performance liquid chromatography (HPLC) was used for the separation and
      quantification of the low molecular-mass organic acids in the root exudates of Cr
      hyperaccumulator Leersia hexandra Swartz. Eight organic acids, oxalic, tartaric,
      formic, malic, lactic, acetic, maleic and citric acids, were separated on an
      XSelect HSS T3 column (250 mm*4.6 mm, 5 MUm) within 13 min with the mobile phase
      of 40 mmol/L potassium dihydrogen phosphate-phosphorous acid at pH 2.40, a flow
      rate of 1.0 mL/min, a detection wavelength of 205 nm and a column temperature of
      25C. This is a simple and highly sensitive method for the separation of the eight
      organic acids with well-shaped peaks. The limits of detection (LODs) for the
      eight acids ranged from 0.12 mg/L to 12.32 mg/L. Under the optimized conditions,
      tartaric, malic, lactic, maleic and citric acids in the root exudates were
      detected with high linearities, acceptable recoveries and excellent precisions.
      The contents of these acids calculated in the root exudates were (130.90+/-1.44)
      MUg/g (root dry weight (DW)) for tartaric acid, (1031.34+/-4.38) MUg/g (root DW)
      for malic acid, (65.54+/-1.01) MUg/g (root DW) for lactic acid, (0.96000+/
      0.00367) MUg/g (root DW) for maleic acid and (201.50+/-1.13) MUg/g (root DW) for
      citric acid. The proposed HPLC method is quite suitable for the simultaneous
      determination of organic acids in the root exudates of Leersia hexandra Swartz,
      and can be used in other plant root exudates as well.

PMID- 29582604
TI  - [One-step extraction method of phthalate esters in vegetable oils].
AB  - In order to develop a fast investigation method for phthalate esters (PAEs) from
      vegetable oils, a gas-liquid micro-extraction (GLME) technique that combined with
      GC-MS was established. A vegetable oil sample (0.1 g) was directly added into the
      GLME device. The integrated process of extraction, clean-up, and concentration of
      PAEs was completed within 5 min. Internal standard method was applied to ensure
      the accuracy of the results. Soybean oil, blend oil, olive oil, and sesame oil
      were spiked with 200 MUg/kg of a mixed 15 PAEs standard, and the ranges of the
      recoveries and RSDs were between 60.0% to 112.3% and 0.9% to 28.4%, respectively.
      Compared with some traditional sample pretreatment methods such as liquid-liquid
      extraction, liquid-liquid micro-extraction, gel permeation chromatography, this
      method is simple and fast, with high accuracy, good repeatability and low matrix
      effect. This study verified the suitability of the GLME method for field
      detection of food products in food safety sector and exhibits great significance
      for the completion of food safety system in China.

PMID- 29582605
TI  - [Enantiomeric separation of D, L-isoleucine in citric acid-zinc (II) medium by
      capillary electrophoresis].
AB  - The enantiomeric separation of unmodified D,L-isoleucine was achieved in citric
      acid-zinc(II) medium by capillary electrophoresis (CE) with contactless
      conductivity detector (C4D). In the conventional chiral separation methods of
      amino acid, a chiral complex used as the chiral selector was added into the
      eluent in order to yield a chiral environment. However, in this study a non
      chiral solution, i. e. 2.8 mmol/L NaOH+0.8 mmol/L citric acid+2.0 mmol/L zinc
      acetate was used as the running buffer, and the citric acid-zinc(II) acted the
      role of a chiral selector. Under the optimum experimental conditions:uncoated
      fused-silica capillary (45 cm*50 MUm, Leff=40 cm), separation voltage of +13 kV,
      electrokinetic injection of 11 kV*8 s, the enantiomers of D,L-isoleucine were
      baseline separated within 8 min with the resolutions (Rs) of 2.0. The calibration
      curve of each enantiomer showed good linearity in the range from 1.0 mg/L to 20
      mg/L, with the limits of detection of 0.40 mg/L. The intra-and inter-day
      precisions were examined. The RSDs of peak area and migration time were found to
      be below 5.0% and 2.5% (n=6), respectively, indicating good repeatability (intra
      day) and reproducibility (inter-day) of the method. Interference experiment was
      also tested. As a result, other common amino acids did not interfere with the
      detection. The proposed method provided a potential new way to further
      investigate the enantioseparation of unmodified or native amino acids.

PMID- 29582606
TI  - [Preparation of monolithic fibers with deep eutectic solvent for solid phase
      microextraction of polycyclic aromatic hydrocarbons in lake water].
AB  - A monolithic fiber of poly(butyl methacrylate-ethylene glycol
      dimethacrylate)[poly(BMA-EDMA)] was prepared using deep eutectic solvent (DES) of
      choline chloride-ethanediol as a porogen. The prepared fibers were applied to
      direct extraction of three polycyclic aromatic hydrocarbons (PAHs) in lake water
      samples by solid phase microextraction (SPME). The extracts were determined by
      ultra performance liquid chromatography (UPLC). The fiber without DES was
      prepared at the same time. Both fibers (with and without DES) were compared with
      a commercial polydimethylsiloxane (PDMS) fiber. The highest extraction efficiency
      was clearly obtained with poly(BMA-EDMA) fiber. The extraction time, extraction
      solvent, desorption time, desorption solvent, and ionic strength were optimized.
      Under the optimum conditions, the linear ranges for the three PAHs (naphthalene,
      biphenyl, and phenanthrene) were 0.1-6.0 mg/L (r >= 0.9903). The limits of
      detection (LODs) of the three PAHs were in the range of 2.1-4.9 MUg/L. The
      recoveries of the three PAHs spiked in lake water samples were 86.4%-111.3% with
      relative standard deviations (RSDs, n=6) of 11.2%-15.1%. This method is simple,
      stable, and inexpensive, and can be used for the determination of the PAHs in
      lake water samples.

PMID- 29582607
TI  - [Determination of 6-benzylaminopurine in edible mushrooms by solid liquid
      extraction with low-temperature partition and high performance liquid
      chromatography-mass spectrometry].
AB  - A simple method based on solid liquid extraction with low-temperature partition
      (SLE-LTP) coupled with high performance liquid chromatography-mass spectrometry
      (HPLC-MS) was developed for the determination of 6-benzylaminopurine (6-BA) in
      edible mushrooms. The samples were extracted with acetonitrile followed by low
      temperature partition at -30C for 4 h. The separation was performed on a Hitachi
      LaChrom C18 column (250 mm*4.6 mm, 5 MUm) with 0.02 mol/L ammonium acetate
      (containing 0.1% (v/v) glacial acetic acid)-methanol (6:4, v/v) as the mobile
      phases with isocratic elution. The compound was detected in positive electrospray
      ionization mode, and quantified by external standard method. The results showed
      that the limit of detection (LOD, S/N>3) for the analyte was 0.006 mg/kg, and the
      limit of quantification (LOQ, S/N>10) was 0.02 mg/kg. The calibration curve
      showed good linear in the range of 0.05-2.0 mg/L, and the correlation coefficient
      (r2) was 1.0000. The spiked recoveries were between 81.3% and 93.7% with the
      relative standard deviations (RSDs, n=6) of 0.7%-2.4% at the spiked levels of 0.1
      mg/kg and 0.5 mg/kg. The developed method is simple, reliable and can be applied
      for the accurate determination of 6-BA residue in edible mushrooms.

PMID- 29582608
TI  - [Determination of myclobutanil and difenoconazole residues in pollen and honey of
      litchi by high performance liquid chromatography-tandem mass spectrometry].
AB  - An effective method was developed for the determination of two major fungicides
      including myclobutanil and difenoconazole residues in pollen and honey of litchi
      by modified QuEChERS-high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS). The pollen and honey samples were all extracted by
      acetonitrile, the pollen samples were cleaned-up by 0.9 g anhydrous magnesium
      sulfate (MgSO4), 0.15 g primary secondary amine (PSA) and 0.15 g C18; the honey
      samples were cleaned-up by 0.9 g MgSO4 and 0.15 g PSA. The 0.1% (v/v) formic acid
      aqueous solution-acetonitrile (25:75, v/v) were used as the mobile phases. The
      extracts were separated on a Poroshell-120 EC-C18 chromatographic column, the
      positive electrospray ion (ESI+) source and selected ion monitoring (SIM) mode
      were used. The analytes were quantified by the matrix matching standard
      solutions. The matrix matched standard solutions of myclobutanil and
      difenoconazole showed good linearities in the range of 1-100 MUg/L, and the
      correlation coefficients (r2) were all above 0.9990. The limits of detection
      (LODs) of myclobutanil and difenoconazole were 0.25 MUg/kg and 0.50 MUg/kg,
      respectively. The limits of quantification (LOQs) of myclobutanil and
      difenoconazole were 0.83 MUg/kg and 1.7 MUg/kg, respectively. The average
      recoveries of myclobutanil and difenoconazole in pollen and honey samples were
      87.0%-95.2% and 90.1%-96.4% with the relative standard deviations of 1.2%-3.6%
      and 0.7%-4.1%, respectively. The method is quick, easy and sensitive, and it is
      suitable for the rapid determination and trace analysis of myclobutanil and
      difenoconazole in pollens and honeys of litchi. The method can provide data
      support for the exposure risk assessment of bees and other pollination insects.

PMID- 29582609
TI  - [Analysis of the heterogeneity of Ralstonia solanacearum avirulent espD-mutant by
      high performance ion-exchange chromatography].
AB  - The heterogeneity of Ralstonia solanacearum avirulent espD-mutant, virulent
      wildtype strain FJAT-91 and spontaneous avirulent strain FJAT-1458 were compared
      and analyzed by using high performance ion-exchange chromatography (HPIEC). Their
      colony and cell morphologies were observed, and the contents of their
      extracellular polysaccharides (EPS) were determined. The results showed that the
      colony and cell morphologies of FJAT-91 ?epsD were different from the original
      strain FJAT-91, but were similar to the spontaneous avirulent strain FJAT-1458.
      The EPS content of FJAT-91 ?epsD was (12.64+/-1.46) MUg/mL, which was much lower
      than FJAT-91 with (30.49+/-2.97) MUg/mL. The strain FJAT-91 were separated into
      single peak of P3 at the retention time of 6.04 min, and FJAT-91 ?epsD had two
      peaks (P1 and P2) at the retention times of 0.59 min and 4.62 min, respectively.
      FJAT-1458 formed single peak of P1 at the retention time of 0.59 min. Then, the
      bacteria eluents from different chromatographic peaks were collected and their
      pathogenicities were detected with bioassay test using potted tomatoes in the
      greenhouse. The results showed that the tomato plants began to wilt 4 d after
      inoculation of strain FJAT-91-P3 eluted from P3, and the disease incidence
      reached 100% at 10 d post inoculation. The strain FJAT-91 ?epsD-P2 eluted from P2
      caused tomato plants wilting 9 d after inoculation, and the disease incidence
      reached 100% at 20 d. During 20 d of observation, none of tomato plants caused
      wilting while inoculation with FJAT-1458-P1 and FJAT-91 ?epsD-P1 eluted from P1
      of FJAT-1458 and FJAT-91 ?epsD, respectively. In this paper, the morphologies,
      EPS contents and chromatographic behaviors of FJAT-91, FJAT-91 ?epsD and FJAT
      1458 were compared, which would provide theoretical basis for using FJAT-91 ?epsD
      to control bacterial wilt disease.

PMID- 29582610
TI  - [Determination of organophosphorus and carbamate insecticide residues in food and
      water samples by solid phase extraction coupled with capillary liquid
      chromatography].
AB  - A method was established for the simultaneous separation and determination of one
      organophosphorus and three carbamate insecticide residues in food and water
      samples by solid phase extraction (SPE) followed by analysis using a home-made
      capillary liquid chromatogram. Various parameters possibly affecting the
      efficiencies of capillary liquid chromatography (CLC) and SPE were investigated
      in detail, such as type of SPE column, pH value of samples, type and volume of
      elution solvent, flow rate of loading sample, salt effect, loading volume,
      detection wavelength, and type and ratio of mobile phases. Under the optimized
      experimental conditions, the four insecticides were separated completely within 6
      min. The limits of detection and limits of quantification were 0.35-1.20 MUg/kg
      and 1.17-4.00 MUg/kg, respectively. Satisfactory recoveries of the SPE-CLC method
      were achieved for spiked food samples of tomato, cucumber and apple ranging from
      72.41% to 107.15% with the relative standard deviations (RSDs) no more than
      8.12%, and for spiked tap/lake water samples ranging from 71.45% to 109.25% with
      the RSDs no more than 9.28%. The method can meet the requirements for multi
      residue analysis of insecticides.

PMID- 29582611
TI  - [Separation of chemical compositions in root of Rumex patientia L. with off-line
      two-dimensional liquid chromatography].
AB  - An innovative analytical method based on the off-line two-dimensional reversed
      phase/reversed-phase liquid chromatography (2D-RPLC/RPLC) was established to
      separate the components of root of Rumex patientia L. The chromatograms of ethyl
      acetate extract of root of Rumex patientia L. on a phenyl/tetrazolium column (250
      mm*4.6 mm, 7 MUm) and a Unitary C18 column (250 mm*4.6 mm, 7 MUm) were compared,
      and they showed different separation abilities. A phenyl/tetrazolium column was
      used for the first dimensional separation with 0.1% (v/v) formic acid aqueous
      solution and methanol as mobile phases, and 18 fractions was collected. The
      second dimensional liquid chromatography analysis was carried out on a Unitary
      C18 column with 0.1% (v/v) formic acid aqueous solution and methanol as mobile
      phases. Based on the experiment setup and results, it was concluded that off-line
      2D-LC can be an effective method for the separation of the trace components and
      the screening of active compounds of root of Rumex patientia L.

PMID- 29582612
TI  - [Determination of fatty acids in natural cream and artificial cream by
      comprehensive two-dimensional gas chromatography-mass spectrometry].
AB  - A method for the determination of 37 fatty acids in natural cream and artificial
      cream was developed by comprehensive two-dimensional gas chromatography-mass
      spectrometry (GC*GC-MS). The samples were extracted with toluene and acetyl
      chloride-methanol (1:9,v/v) solution was added to the extract for fat
      esterification. Finally, the fatty acids were analyzed by GC*GC-MS. The GC
      conditions were as follows:a DB-5 column (30 m*0.25 mm*0.25 MUm) was set as the
      1st dimensional column and a BPX-50 column (2.5 m*0.1 mm*0.25 MUm) was the 2nd
      dimensional column. The primary oven temperature was programmed from 50C (held
      for 2 min) to 180C at a rate of 20C/min, followed by an increase to 250C at
      2.5C/min, then raised up to 300C (held for 5 min) at 3C/min. The ion source
      temperature was 200C with auxiliary temperature of 300C in scan mode. All fatty
      acids were separated effectively and determined accurately while the modulation
      period was 5s and the scan range of MS was m/z 40-385. This procedure was applied
      to analyze the fatty acids in commercial natural cream and artificial cream from
      Chinese markets, among which we found the characteristic components in different
      kinds of samples. Compared with gas chromatography-flame ionization detector (GC
      FID), GC*GC-MS method was more sensitive and more components of fatty acids were
      detected. Conclusively, this work suggests a new technical approach in analyzing
      fatty acids in natural cream and artificial cream, which is meaningful to ensure
      the quality identification and safety of natural cream.

PMID- 29582613
TI  - [Determination of 16 polycyclic aromatic hydrocarbons in marine sediments by gas
      chromatography-tandem mass spectrometry with accelerated solvent extraction].
AB  - A method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) with
      accelerated solvent extraction (ASE) was developed for the determination of 16
      polycyclic aromatic hydrocarbons (PAHs) in marine sediments. The sediment samples
      were extracted with hexane-acetone (1:1, v/v). The extracts were dehydrated with
      anhydrous sodium sulfate, and concentrated with a termovap sample concentrator.
      The concentrated solutions were further cleaned up with Si SPE columns. The
      purified solutions were then isolated by HP-5MS column (30 m*0.25 mm*0.25 MUm).
      The analytes were detected using electron impact source under multiple reaction
      monitoring (MRM) mode. The results showed that the 16 PAHs had good linearities
      in the range of 0.01-1.00 mg/L with the correlation coefficients (R) greater than
      0.997. The spiked recoveries of the 16 PAHs were in the range of 75.8%-97.8%, and
      the relative standard deviations (RSDs) were less than 10%. The method detection
      limits (MDLs) of the 16 PAHs ranged from 0.048-0.234 MUg/kg with 20.0 g sampling
      weight. This method is suitable for the determination of trace PAHs in marine
      sediments.

PMID- 29582614
TI  - [Rapid resolving algorithm of gas chromatographic overlapping peaks based on the
      asymptotic expansion of integration].
AB  - A novel algorithm, called asymptotic expansion of integration, is suggested to
      resolve gas chromatographic overlapping peaks. There are three steps for the
      algorithm. First, a valley peak or a shoulder peak is separated into two domains,
      and an integral equation on a subdivision and an algebraic equation on the
      overlapping peak domain are listed. Secondly, areas needed in two equations, are
      computed by a numerical integral method, then the integral equation is expended
      to an algebraic equation by the asymptotic formula of integration. At last,
      combing two equations with constraint equations of peak heights, we got a
      nonlinear algebraic set. The equation set can be solved rapidly by Gauss-Seidel
      iteration, and the maximum number of iterations is not more than 20 times. The
      simulation and experimental results showed that height and area errors of
      resolving peaks are quite small, the maximum error of area is less than 6.44%,
      and that of the height is about 6.80%. Because of the high accuracy and
      computational efficiency, the algorithm can be used in decomposition of gas
      chromatographic overlapping peaks and online real-time processing of general
      chromatographic overlapping peaks.

PMID- 29582615
TI  - [Investigation on the interaction between pentadecafluorooctanoic acid and human
      serum albumin by capillary electrophoresis].
AB  - Capillary electrophoresis (CE) has been used to establish the analytical method
      of interaction between pentadecafluorooctanoic acid (PFOA) and human serum
      albumin (HSA). Under the physiological conditions, the interaction model of PFOA
      and HSA were constructed. Mobility method, plug-plug kinetic (PPK) method and
      simplified Hummel-Dreyer method were used to determine the interaction between
      derivatives and HSA. Non-linear regression, Scatchard equation and Klotz equation
      were adopted to obtain the interaction parameters. The results showed that all
      the three methods can be used to analyze the interaction of PFOA-HSA system.
      According to the interaction parameters, the most suitable CE method is
      simplified Hummel-Dreyer method while the most suitable theoretical equation is
      non-linear regression. The binding parameters indicated that the interaction of
      PFOA-HSA system has only one type of binding sites and the binding is stable. The
      research results have illustrated the interaction between HSA and PFOA, and
      provided a beneficial reference for in-depth research of the toxic mechanism of
      PFOA.

PMID- 29582616
TI  - [Determination of cyanamide residue in grapes and cherries by liquid
      chromatography-tandem mass spectrometry coupled with precolumn derivatization].
AB  - A method was developed for the quantitative determination of cyanamide in grapes
      and cherries by liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled
      with dansyl chloride (DNS) precolumn derivatization. First, the samples were
      homogenized, and then extracted with ethyl acetate under ultrasonication. The
      water was removed using anhydrous sodium sulfate, and the extract was
      concentrated and derivatized with dansyl chloride under alkaline condition. The
      separation was performed on a Shimadzu Shim-pack XR-ODS column (75 mm*2.0 mm, 1.6
      MUm) with the mobile phases of methanol and 2 mmol/L ammonium acetate aqueous
      solution (containing 0.05% (v/v) formic acid) in a gradient elution mode. The
      identification and quantification of cyanamide were carried out by MS/MS in
      positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM)
      mode. The calibration curves showed good linearities in the range of 0.01-1.0
      mg/L with the correlation coefficients not less than 0.9990. The average
      recoveries of cyanamide spiked at 0.01, 0.05 and 1.0 mg/kg in cherries and grapes
      were between 75% and 81%, and the relative standard deviations (RSDs) were
      between 6.5% and 9.8%. Both the limits of quantification (LOQs) of the analytes
      were 0.01 mg/kg. The method is simple, rapid, accurate and suitable for the
      confirmation and quantification of cyanamide in cherries and grapes.

PMID- 29582617
TI  - Real world use of biological drugs in patients with psoriasis/psoriatic
      arthritis: a retrospective, population-based study from Southern Italy in the
      years 2010-2014.
AB  - BACKGROUND: Biological drugs, such as infliximab, etanercept, adalimumab,
      ustekinumab, golimumab and certolizumab are third-line therapy for psoriasis
      (PsO) and psoriatic arthritis (PsA), but they may be used at earlier stage in
      severe forms. This study investigated the pattern of use and costs of biological
      drugs for PsO/PsA in a large population from Southern Italy during the years 2010
      2014. METHODS: This was a retrospective, population-based, drug-utilization
      study, using healthcare administrative databases of the Local Health Unit and two
      hospitals of Messina Province (Sicily) in the years 2010-2014. Incident users of
      adalimumab, ustekinumab, infliximab, etanercept and golimumab for PsO/PsA were
      characterized. Yearly prevalence of use and costs, as well as time to treatment
      discontinuation and switch were assessed. RESULTS: During the study period, 517
      patients received at least one study drugs prescription for PsO/PsA and 304
      (58.8%) were incident users, mostly treated with adalimumab (33.6%). Incident
      users were mostly males (59.8%), with a median age of 49 years. Prevalence of
      biological drugs users in PsO/PsA increased from 4.3 to 6.9 per 10,000
      inhabitants from 2011 to 2014. Pharmaceutical expenditure of the study drugs
      almost doubled (from 2.6 to 4.7 million euros during 5 observation years). During
      the first year of treatment, discontinuation occurred in 31.8% of incident users
      and switch was not infrequent (7.4%). CONCLUSIONS: Prevalence of use and costs of
      biological drugs for PsO/PsA substantially increased in recent years in a large
      population of Southern Italy. Larger uptake of lowest cost biological drugs, and
      biosimilars whenever available, may help access to the most innovative drugs.

PMID- 29582618
TI  - Comparison of clinical effects, trough and peak levels between branded and
      generic formulation of Cyclosporine in stable psoriatic patients.
AB  - BACKGROUND: Cyclosporine A (CyA) is a drug for moderate-to-severe psoriasis.
      Recently, a generic formulation has been approved as bioequivalent to the branded
      one. The guidelines for the bioequivalence for critical-dose drugs with a narrow
      therapeutic range, such as CyA, are questionable. Therefore, it is important to
      assess the clinical outcome and the pharmacokinetics of different formulations in
      various patient groups. The current literature lacks of this information in
      dermatology. The primary objective of this prospective study is to investigate
      the clinical equivalence (in terms of maintenance of clinical effect) between the
      generic formulation of CyA and its branded one in patients with psoriasis. A
      secondary objective is to analyze their trough (C0) and peak levels (C2).
      METHODS: Twenty patients with stable psoriasis under treatment with the branded
      CyA were monitored in terms of clinical efficacy (Psoriasis Area Severity Index-
      PASI), safety (laboratory values), and their pharmacokinetics utilizing trough
      (C0) and peak plasma concentration (C2). The same patients were subsequently
      shifted to the generic formulation for comparison. RESULTS: In our sample the
      efficacy of the two formulations was equal in most cases (p=0.863). A non
      significant difference between the C0 and C2 of the branded CyA compared to the
      generic one emerged (respectively p=0.738 and p=0.695). CONCLUSIONS: The branded
      and the generic formulations of CyA seem to be not only bioequivalent, but also
      comparable in terms of clinical efficacy in patients with psoriasis. However,
      larger samples are required to confirm these findings.

PMID- 29582619
TI  - Oral Echinacea exerts complete clearing of multiple facial molluscum contagiosum
      in a young black patient.

PMID- 29582620
TI  - Is HERV-K and HERV-W expression regulated by mir-155 in Sezary syndrome?
AB  - BACKGROUND: According to the latest update, 2578 unique mature miRNAs are
      currently annotated in the human genome and participate in the regulation of
      multiple events, such as cellular proliferation or apoptosis. A previous study
      analyzing global miRNA expression patterns in GH cells (high HERV-K versus low)
      showed that two miRNAs (miR-663 and miR-638) are differentially regulated and
      exhibit expression parallel to that of HERV-K. The aim of this study was to
      evaluate HERV-K and -W pol gene and mir-155 expression in SS patients and
      possible relationship between them. METHODS: The comparison between SS patients
      and healthy donor showed a significant difference in terms of mir-155 expression
      p=0.0003 as previously reported by our groups. RESULTS: We demonstrated that HERV
      K and -W pol gene expression was significantly higher in SS patients vs healthy
      donor as previously reported by our groups. Our correlation data suggest that miR
      155 are not directly involved in regulating the HERVs. CONCLUSIONS: Furthermore,
      further studies including other cohorts of pathology with mir-155 and HERVs
      involvement such as inflammatory diseases are needed to investigate the role of
      mir-155 in the cross-activations of HERVs.

PMID- 29582621
TI  - Asymmetric periflexural exanthem: not a distinctive disease of childhood.

PMID- 29582622
TI  - Urticaria associated with Epstein-Barr virus reactivation. Cutaneous
      manifestations of Epstein-Barr virus.

PMID- 29582623
TI  - Effect of direct intramyocardial autologous stem cell grafting in the sub-acute
      phase after myocardial infarction.
AB  - BACKGROUND: To assess the efficacy and safety of intramyocardial autologous bone
      marrow mononuclear stem cells (BMMNC) grafting combined with coronary artery
      bypass grafting (CABG) on ventricular remodeling and global and regional wall
      motion after acute transmural myocardial infarction (AMI). METHODS: Randomized
      controlled trial including 20 patients with non-revascularized transmural AMI,
      left ventricular ejection fraction (LVEF) lower than 50% and surgical indication
      for CABG. The stem cell group was treated with BMMNC grafting by direct
      intramyocardial injection between the 10th and 15th days after AMI (subacute
      phase) combined with CABG under cardiopulmonary bypass; the control group was
      only treated with CABG. Magnetic resonance imaging with gadolinium and stress
      echocardiography were performed presurgery and 9 months postsurgery. RESULTS:
      Seventeen patients completed the follow-up. The baseline characteristics of both
      groups were homogeneous. No significant differences were found in the increase in
      LVEF (control: 6.99+/-4.60, cells: 7.47+/-6.61, P=0.876) or in the decrease in
      global (control: 0.28+/-0.39, cells: 0.22+/-0.28, P=0.759) or regional (control:
      0.52+/-0.38, cells: 0.74+/-0.60, P=0.415) wall motion indices between the control
      and stem cell groups of AMI patients. No differences were found in the recovered
      non-viable segments (control: 1.29+/-1.11, cells: 2.50+/-1.41, P=0.091) or in the
      decrease in end-diastolic (control: 14.05+/-19.72, cells: 18.40+/-29.89, P=0.725)
      or end-systolic (control: 15.42+/-13.93, cells: 23.06+/-25.03, P=0.442) volumes.
      No complications from stem cell grafting were observed. CONCLUSIONS: The results
      from our study reported herein suggest that intramyocardial BMMNC administration
      during CABG in patients with AMI causes no medium- to long-term improvement in
      ventricular remodeling.

PMID- 29582624
TI  - Carotid endarterectomy: a world of discrepancies.

PMID- 29582625
TI  - Lower limb ischemia management in acute Stanford type A aortic dissection.

PMID- 29582626
TI  - Gender Differences in the Recurrence Timing of Patients Undergoing Resection for
      Non-Small Cell Lung Cancer
AB  - Objective: This study was designed to visually represent postoperative recurrence
      patterns using event dynamicsand to assess sex-based differences in the timing of
      recurrence for non-small cell lung cancer. Methods: We studied829 patients (538
      men, 291 women) with NSCLC who underwent complete pulmonary resection in 9
      hospitals. Eventdynamics with the use of life-table methods were evaluated, and
      only first events (distant metastases or local recurrence)were considered. The
      effects of sex, histological type, pathological stage, and smoking history were
      studied. Result:The resulting smoothed hazard rate curves indicated that the
      recurrence risk pattern definitely correlated with sex, witha sharp peak in the
      first year in men and a broad peak during the first 2 to 3 years in women. These
      findings were alsoconfirmed by analyses according to pathological stage,
      histological type, and smoking history. Conclusion: The peaktimes of recurrence
      differed considerably between men and women. The delayed time of peak recurrence
      in women,associated with a longer disease-free interval within subsets of
      patients with similar disease stage, histological type,and smoking status, might
      account for the better survival in women.

PMID- 29582627
TI  - ADH1B, ALDH2, GSTM1 and GSTT1 Gene Polymorphic Frequencies among Alcoholics and
      Controls in the ArcadianPopulation of Central India
AB  - Background: Epidemiological research has highlighted the global burden of primary
      liver cancer cases due toalcohol consumption, even in a low consumption country
      like India. Alcohol detoxification is governed by ADH1B,ALDH2, GSTM1 and GSTT1
      genes that encode functional enzymes which are coordinated with each other to
      removehighly toxic metabolites i.e. acetaldehyde as well as reactive oxygen
      species generated through detoxification processes.Some communities in the
      population appears to be at greater risk for development of the liver cancer due
      to geneticpredispositions. Methods: The aim of this study was to screen the
      arcadian population of central India in order toinvestigate and compare the
      genotype distribution and allele frequencies of alcohol metabolizing genes
      (ADH1B,ALDH2, GSTM1 and GSTT1) in both alcoholic (N=121) and control (N=145)
      healthy subjects. The gene polymorphismanalysis was conducted using PCR and RFLP
      methods. Results: The allele frequency of ALDH2 *1 was 0.79 and ofALDH2*2 was
      0.21 (OR:1.12; CI (95%): 0.74-1.71). The null allele frequency for GSTM1 was 0.28
      (OR:0.85; CI(95%): 0.50-1.46) and for GSTT1 was 0.20 (OR:1.93; CI (95%): 1.05
      3.55). No gene polymorphism for ADH1B wasnot observed. The total prevalence of
      polymorphisms was 3.38% for ALDH2, GSTM1 and GSTT1. Conclusion: Theresults of
      this study suggested that individuals of the Central India population under study
      are at risk for liver disordersdue to ALDH2, GSTM1 and GSTT1 gene polymorphisms.
      This results may have significance for prevention of alcoholdependence, alcoholic
      liver disorders and the likelihood of liver cancer.

PMID- 29582628
TI  - Self-Confidence and Quality of Life in Women Undergoing Treatment for Breast
      Cancer
AB  - Introduction: Quality of life is an important topic in the study of chronic
      diseases, especially cancer which can havea major effect on patient self
      confidence. This study was conducted to determine quality of life and its
      relationship withself-confidence in women undergoing treatment for breast cancer.
      Methods: This cross-sectional, descriptive, analyticalstudy was conducted in 2016
      on 166 women with breast cancer undergoing treatment at Ghazi, Al-Zahra,
      Internationaland/or Shams hospitals in Tabriz. The subjects were selected through
      convenience sampling. A personal-demographicquestionnaire, the Cancer Quality of
      Life Questionnaire (QLQ-C30), and the Rosenberg Self-Esteem Scale (RSES)
      werecompleted for each patient. The data obtained were analyzed using independent
      t-tests, one-way ANOVA, multivariatelinear regression and Pearson's correlation
      coefficients. Findings: The mean total score of quality of life was 59.1+/
      17.4,ranging from 0 to 100. The highest mean score was obtained in the cognitive
      subscale (74.9+/-23.8) and the lowest in theemotional subscale (51.4+/-21.1). The
      mean score for self-confidence was 0.3 with a standard deviation of 0.1,
      rangingfrom -1 to +1. There was a significant positive relationship between self
      confidence and quality of life, except in threesymptom subscales for diarrhea,
      constipation and loss of appetite (P<0.05). Self-confidence, disease duration,
      lifestyle,marital satisfaction and caregiver status were among the predictors of
      quality of life. Discussion: Given the significantrelationship between quality of
      life and self-confidence, health care providers may need to pay special attention
      towomen undergoing treatment for breast cancer and perform timely measures to
      maintain their belief in themselves.

PMID- 29582629
TI  - Urinary Metabolomic Profiling in Chronic Hepatitis B Viral Infection Using Gas
      Chromatography/Mass Spectrometry
AB  - Background: Chronic hepatitis B (CHB) can lead to cirrhosis and hepatocellular
      carcinoma. The metabolomicprofiling has been shown to be associated with
      pathogenic mechanisms in many medical conditions includingCHB. The purpose of
      this study was to investigate the urine metabolomic profiles in CHB patients by
      gaschromatography/mass spectrometry (GC/MS). Methods: Urine samples were
      collected from CHB patients (n = 20)and normal control subjects (n = 20).
      Metabolite profiles were assessed using GC/MS in conjunction with
      multivariatestatistical analysis, in order to identify biomarker metabolites.
      Pathway analysis was performed by MetaboAnalyst3.0 and KEGG database.Results:
      Twelve out of 377 metabolites were shown to be significantly different between
      theCHB and normal control groups (p < 0.05). These include palmitic acid, stearic
      acid, oleic acid, benzoic acid, butanoicacid, cholesterol, glycine, 3-heptanone,
      4-heptanone, hexanal, 1-tetradecanol and naphthalene. Multivariate
      statisticalanalysis constructed using these expressed metabolites showed CHB
      patients can be discriminated from healthy controlswith high sensitivity (95%)
      and specificity (85%). All the metabolic perturbations in this disease are
      associated withpathways of fatty acid, amino acid, bile acid and gut microbial
      metabolism. Conclusion: CHB patients have a specificurinary metabolomic profile.
      The abnormalities of fatty acid, amino acid, bile acid, and gut microbial
      metabolism leadto the development of disease progression. GC/MS-based assay is a
      promising tool for the metabolomic study in CHB.

PMID- 29582630
TI  - Comparison of Survival Models for Analyzing Prognostic Factors in Gastric Cancer
      Patients
AB  - Objective: There are a number of models for determining risk factors for survival
      of patients with gastric cancer.This study was conducted to select the model
      showing the best fit with available data. Methods: Cox regression andparametric
      models (Exponential, Weibull, Gompertz, Log normal, Log logistic and Generalized
      Gamma) were utilized inunadjusted and adjusted forms to detect factors
      influencing mortality of patients. Comparisons were made with AkaikeInformation
      Criterion (AIC) by using STATA 13 and R 3.1.3 softwares. Results: The results of
      this study indicated thatall parametric models outperform the Cox regression
      model. The Log normal, Log logistic and Generalized Gammaprovided the best
      performance in terms of AIC values (179.2, 179.4 and 181.1, respectively). On
      unadjusted analysis,the results of the Cox regression and parametric models
      indicated stage, grade, largest diameter of metastatic nest,largest diameter of
      LM, number of involved lymph nodes and the largest ratio of metastatic nests to
      lymph nodes,to be variables influencing the survival of patients with gastric
      cancer. On adjusted analysis, according to the best model(log normal), grade was
      found as the significant variable. Conclusion: The results suggested that all
      parametric modelsoutperform the Cox model. The log normal model provides the best
      fit and is a good substitute for Cox regression.

PMID- 29582631
TI  - Effect of an Educational Intervention Based on Protection Motivation Theory on
      Preventing Cervical Cancer amongMarginalized Women in West Iran
AB  - Objective: This study aimed to determine the effectiveness of an educational
      intervention to prevent cervical canceramong marginalized Iranianwomen based on
      the Protection Motivation Theory (PMT) as a theoretical framework.Methods: This
      quasi-experimental study was carried out on 143 women of Kermanshah City in
      western Iran during2017. Participants were recruited through cluster and simple
      random sampling and randomly divided into experimental(n=72) and control groups
      (n=71). All completed a self-administered questionnaire including PMT constructs
      anddemographic variables. An intervention over six sessions was then applied to
      the experimental group. Reassessmentwas conducted three months after the
      intervention, with data was analyzed with SPSS-16 using chi-square,
      McNemar,paired T- and independent T-tests. Results: The mean scores for the
      constructs of PMT, and cervical cancer screeningbehavior showed no significant
      differences between the two groups before the intervention (P>0.05). The
      educationalmanipulation had significant effects on the experimental groups'
      average response for perceived vulnerability, perceivedseverity, perceived
      reward, self-efficacy, response efficacy, response cost and protection motivation
      (all p < 0.001).Also, the prevalence of regular Pap smear testing and referral to
      health centers were significantly increased after 3months in the experimental
      (P=0.048), but notthe control group (P>0.05). Conclusions: The results show that
      applyingan educational intervention based on PMT might help prevent cervical
      cancer and improve regular Pap smear testing.

PMID- 29582633
TI  - Cancer-Related Pain: Prevalence, Severity and Management in a Tertiary Care
      Center in the Middle East
AB  - Background: Despite pain awareness and the development of treatment guidelines,
      cancer-related pain assessmentand management remain suboptimal. Our objectives
      were to estimate the prevalence and severity of pain and itsinterference with
      daily activities, and evaluate adequacy of treatment in cancer patients in
      Lebanon. Methods: Atotal of 400 cancer patients aged 18 and above were
      interviewed at the American University of Beirut Medical Centersurgical and
      medical oncology floors, outpatient clinics and chemotherapy units from March
      2016-February 2017. Thesubjects covered were socio-demographics, clinical data,
      and presence of pain in the past month with use of the BriefPain Inventory
      questionnaire. Descriptive statistics were conducted using t-test, chi-square and
      Fischer's exact tests.Pearson's correlation coefficients were used to examine
      relationships between pain severity and pain interference.Logistic regression was
      employed to determine risk factors for pain. Results: The majority of
      participants were Lebanese(76.0%), females (62.7%), married (80.2%), of Muslim
      faith (64.2%), of urban residence (85.8%), and with insuranceplans (81.3%). Most
      had breast cancer (38.8%), were stage 4 (52.7%) and underwent a combination of
      surgery andsystemic therapy (55.1%). The prevalence of pain in the past month was
      29.8%. Among patients with pain, the highestproportion had moderate pain (37.8%)
      and around 46% received inadequate treatment. Conclusion: More awarenessabout
      cancer-related pain is needed to improve pain management and encourage referral
      to palliative care and painspecialists early-on in diagnosis of disease.

PMID- 29582632
TI  - Accuracy of Specimen Radiography in Assessing Complete Local Excision with Breast
      Conservation Surgery
AB  - Objective: The aim of this study was to evaluate the accuracy of "X- ray
      examination of surgicallyresected specimen'' in assessing complete local excision
      (CLE). Materials and Methods: In this retrospective crosssectional study, data
      were collected for all female breast cancer cases who underwent breast-conserving
      surgery afterneedle localization of mammographically visible disease. Males,
      patients with mammographically invisible diseaseand cases with benign or
      inconclusive histopathology, those undergoing modified radical mastectomy and
      individualswith dense breast parenchyma were excluded. We evaluated radiography
      of resected specimens to assess marginspiculation, distance of
      mass/microcalcification from the excised margin, presence of a mass, and presence
      of anyadjacent microcalcification, Other features including mass size, nuclear
      grade and patient's age were also recorded andall were analyzed for any
      association with CLE. Results: Absence of adjacent microcalcification and the
      presence of amass on radiographs showed significant associations with CLE, but no
      links were evident with other features. Specimenradiography was found to be a
      sufficient tool to predict CLE with a positive predictive value of 83.3%, a
      sensitivity of80.7% and a specificity of 81%. Conclusion: Specimen radiography is
      an important and sensitive tool to predict CLE.

PMID- 29582634
TI  - Characterization of Apoptosis in a Breast Cancer Cell Line after IL-10 Silencing
AB  - Background: Breast cancer is affected by the immune system in that different
      cytokines play roles in its initiationand progression. Interleukin-10 (IL-10), an
      anti-inflammatory cytokine, is an immunosuppressive factor involved
      intumorigenesis. The present study was conducted to investigate the gene
      silencing effect of a small interference RNA(siRNA) targeting IL-10 on the
      apoptotic pathway in breast cancer cell line. Methods: The siRNA targeting IL-10
      anda glyceraldehyde 3-phosphate dehydrogenase (GAPDH) clone were introduced into
      MDA-MB-231 cells. Real-timePCR assays were used to determine IL-10 and GAPDH gene
      expression levels, in addition to those for protein kinaseB (AKT),
      phosphoinositide 3-kinase (PI3K), B-cell lymphoma 2 (Bcl2), caspase-3 and caspase
      9 genes related toapoptosis. Results: Inhibition of IL-10 by the siRNA
      accelerated apoptosis and was accompanied by significantincrease in caspase-3 and
      caspase-9 and a significant decrease in PI3K, AKT and Bcl2 expression levels
      compared tothe non-transfected case. Conclusions: In conclusion, the production
      of IL-10 may represent a new escape mechanismby breast cancer cells to evade
      destruction by the immune system. IL-10 gene silencing causes down regulation of
      bothPI3K/AKT and Bcl2 gene expression and also increases the Bbc3, BAX caspase3,
      and caspase 3 cleavage expressionlevels. IL-10 might represent a promising new
      target for therapeutic strategies.

PMID- 29582635
TI  - Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering
      from Genital Neoplasia
AB  - Objective: Persistence of HPV infection is the true cause of cervical disorders.
      It is reported that competitionmay exist among HPV genotypes for colonization.
      This survey was designed to establish the multiple HPV genotypestatus in our
      community and the probability of multiple HPV infections involvement. Methods:
      All multiple HPVinfections were selected for investigation in women suffering
      from genital infections referred to private laboratoriesin Tehran, Iran. A total
      of 160 multi HPV positive specimens from cervical scraping were identified by the
      HPVgenotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV
      6 (LR), 16 (HR), 53 (pHR), 31(HR) and 11 (LR) were included in 48.8% of detected
      infections as the most five dominant genotypes. HPV 16 wasdetected at the highest
      rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51
      and 56in concurrent infections. It appears that HPV 16 and 53 may have
      significant tendencies to associate with each otherrather than with other
      genotypes. Analysis of the data revealed there may be some synergistic
      interactions with a fewparticular genotypes such as "HPV 53". Conclusion:
      Multiple HPV genotypes appear more likely to be linked withdevelopment of
      cervical abnormalities especially in patients with genital infections. Since,
      there are various patternsof dominant HPV genotypes in different regions of
      world, more investigations of this type should be performed forcareHPV programs
      in individual countries.

PMID- 29582636
TI  - Individual and Integrated Effects of Potential Risk Factors for Oral Squamous
      Cell Carcinoma: A Hospital-Based Case-Control Study in Jazan, Saudi Arabia
AB  - Background: Oral cancer is the sixth most common cancer in the world, with a high
      prevalence reported in Jazanprovince of Saudi Arabia. The objectives of this
      study were to check individual and integrated effects of potential riskfactors
      for oral squamous cell carcinoma. Materials and methods: A case control study was
      designed with a sampleof 210 subjects, in which histopathologically confirmed
      incident cases (n=70) and controls (n=140) matched for age,gender and referral
      route, were recruited. Differences in exposure to potential risk factors between
      cases and controlswere assessed using chi-square and McNemar analyses. A logistic
      regression model with interactions was applied to checkindividual and integrated
      effects. Results: Mean age of the sample was 55 years (+ 20 years). Shammah (O.R
      = 33.01;C.I = 3.22 - 39.88), shisha (O.R = 3.96; C.I = 0.24 - 63.38), and
      cigarette (O.R = 1.58; C.I = 0.13, 2.50) consumptionwas significantly associated
      (P<0.05) with oral squamous cell carcinoma development. In contrast, Khat chewing
      (O.R= 0.67; C.I = 0.19-2.36) was without significant effect. An increase in odds
      ratios was observed when combinationsof shammah and shisha (O.R = 35.03; C.I =
      11.50-65.66), shisha and cigarettes (O.R = 10.52; C.I = 1.03 - 33.90) orshamma
      and cigarettes (O.R = 10.10; C.I = 0.50 - 20.40) were used. Conclusion: Combined
      exposure to risk-factorshas serious implications and policies on oral cancer
      prevention should be designed with attention to this aspect.

PMID- 29582637
TI  - Swallowing Exercises: Will They Really Help Head and Neck Cancer Patients?
AB  - Purpose: The work was a comparative study, the aim of which is to evaluate the
      impact of swallowing exercises onswallowing problems among head and neck cancer
      patients (HNCPs) after CRT. Methods: The sample of 60 HNCPswas equally divided
      into control and study groups. The investigators met all patients 3 times
      (before, during and afterCRT); swallowing ability was assessed using the Sydney
      Swallowing Questionnaire (SSQ). The University of Texas,MD Anderson Cancer Center
      Swallowing Exercise Protocol was explained and demonstrated by the investigators
      tothe study group. All tools used were translated into Arabic. Data analyses were
      carried out using the statistical packagefor social sciences (SPSS), program
      version 20. Results: Most of the patients from both groups experienced
      milddysphagia during the 1st visit. By the 3rd visit, severe dysphagia (to thin
      and thick liquids, and soft and hard food)was higher in the control group (73.3%)
      compared to the study group (26.7%). By the third visit there was
      statisticallysignificant difference between both groups in swallowing thin
      liquids (p = 0.01), as well as thick liquids (p = 0.01).At the 1st visit, there
      was no significant difference regarding swallowing soft food (p = 0.24), hard
      food (p = 0.17),dry food (p = 0.89) and swallowing Saliva (p = 0.28). While by
      the 3rd visit, there was significant difference betweencontrol and study groups
      in all parameters. Conclusions: Adequate prevention and treatment of dysphagia,
      with useof swallowing programs, is essential to plan a complete therapeutic
      programme.

PMID- 29582638
TI  - Extraction and Characterization of Chick PEA (Cicer arietinum) Extract with
      Immunostimulant Activity in BALB/C MICE
AB  - Traditional plant medicines are used for a range of cancer conditions. The
      chickpea is highly proteinaceous andconsumed as a staple in many parts of the
      world. An evaluation of chemoprotective and immunomodulatory activitiesof Cicer
      arietinum (CE) in cisplatin-induced immunosuppressed mice was here performed.
      Cisplatin was givenat 100mg/kg, intraperitoneally, and after induction of
      immunosuppression mice were treated with Cicer arietinum(0.5 mg/dose/animal/IP)
      for a period of 10-day. The influence of the extract on lymphoid organ weight,
      bone marrowcellularity, alpha esterase activity and on enzyme levels such as
      (SGOT,SGPT, Urea, Creatinine was assessed toidentify any chemoprotective
      influence. Administration of CE to cisplatin-treated mice alleviated the drastic
      reductionin bone marrow cellularity and alpha- esterase positive cells seen with
      cisplatin. Thus myelosuppression was reversed orinhibited. Cisplatin bids to DNA
      and causes damage resulting in chromosome breaks, micronucleus formation and
      celldeath. CE is comprised of numerous middle-chain aliphatic alcohols, aldehydes
      and ketones, in addition to compoundslike 7-hydroxy-1-methoxy-6
      methylanthraquinone, cyclohexadecane (CAS) and 6-(amino methyl)-2-naphthol.
      Theselatter are thought to contribute to the characteristic aroma of C.
      arietimnum. In conclusion, administration of CEin cisplatin-treated mice, boosted
      bone marrow cellularity and increased alpha- esterase positive cells, thus
      reversingmyelosupproession.

PMID- 29582640
TI  - Effectiveness of a Mass Media Campaign on Oral Carcinogens and Their Effects on
      the Oral Cavity
AB  - Objective: To develop a mass media campaign on oral carcinogens and their effects
      on the oral cavity in orderto increase awareness among the general population.
      Methods: Documentary and public service announcementshighlighting the effects of
      tobacco and its products were designed and developed based on principles of
      behavior change. Aquestionnaire, designed to determine the knowledge, attitude
      and practice of people regarding oral carcinogens, was usedto conduct a baseline
      survey at various sites in eastern Nepal. Local television channels and radio
      stations broadcastedthe documentary and public service announcements. An
      evaluation survey was then performed to assess the effectivenessof the campaign.
      Results: Baseline and evaluation surveys covered 1,972 and 2,140 individuals,
      respectively. A thirdof the baseline population consumed quid, 22% chewing
      tobacco, 16% gutka (commercial preparation of arecanut,tobacco, lime and
      chemicals) and 25% cigarettes. Tobacco consumption differed significantly between
      3 ecologic regionswith greater use in the Terai region. The knowledge prevalence
      regarding the oral carcinogens quid (70%), chewingtobacco (82%), gutka (58%) and
      cigarettes (93%) significantly increased in the evaluation population. Females
      weremore aware about the various tobacco products and their effects on health.
      More people knew about the harmful effectsof tobacco on their health and oral
      cavity, and had their mouth examined and the frequency of consumption of
      theseproducts reduced significantly after the campaign. Attitudes towards
      production, sale and advertisements of tobaccoalso improved significantly.
      Conclusions: The mass media campaign was an effective tool for increasing
      awarenessamong the population.

PMID- 29582639
TI  - Diagnostic Value of Glypican-3 for Hepatocellular Carcinomas
AB  - Background: Hepatocellular carcinoma (HCC) is a common and dangerous malignancy
      in many parts of the world,and especially in Egypt. Early diagnosis is the most
      important step in successful HCC management. However mostcases are detected at
      late stage making effective intervention impossible. Aim: The aim of this study
      was to evaluatethe potential of Glypican-3 (GPC-3) to aid in diagnosis of HCC,
      especially in patients with low serum alpha-fetoprotein(AFP). Subjects and
      methods: Serum GPC-3 was assessed by flow-cytometry and serum AFP by enzyme
      linkedimmunosorbent assay (ELISA) in 40 HCC patients with AFP< 400ug?l. (GI), 40
      HCC patients with AFP> 400ug?l.(GII) and 20 healthy controls (GIII). Results: GPC
      3 was found to be significantly elevated in HCC as compared tohealthy subjects
      (GI 38.2+/-22. 5, GII 50.2+/-22.6, and GIII 2.24+/-1.19), with sensitivities of
      85% for GI and 84% for GIIand specificities of 95% for GI and 92% for GII. AFP
      showed respective sensitivities of 50% and 79%, and specificitiesof 80% and 90%,
      for HCC diagnosis. The combination of GPC-3 with AFP achieved the highest
      sensitivity (98.5%) andspecificity (97.8%). Conclusion: Serum GPC-3 has a better
      sensitivity than AFP for the diagnosis of HCC. Combinationof two markers appears
      warranted for greatest accuracy.

PMID- 29582641
TI  - Factors Affecting Uptake of Cervical Cancer Screening Among African Women in
      Klang Valley, Malaysia
AB  - Introduction: Cervical cancer is a health concern among women worldwide,
      presently ranking as the second to fourthcommon cancer type among women in
      different parts of the world. Human papillomaviruses (HPV) 16 and 18 are themain
      causative agents of cervical cancer. However, prevention is possible with early
      and regular cervical cancer screening.Objective: This study aimed to identify the
      cervical cancer screening practices and factors affecting the screeningstatus of
      African immigrant women attending selected church services in Klang Valley,
      Malaysia. Methodology:A cross-sectional study among 320 randomly selected
      respondents between ages 18-69 was conducted in three differentchurches with high
      numbers of African participants. A self-administered questionnaire was
      distributed among therespondents. To ensure a good understanding, the
      questionnaire was written and self-explained in English language,because English
      is the general spoken language among the study population. Three levels of
      analysis were conductedusing SPSS 21, involving descriptive analysis, chi square
      and multiple logistic regression. Results: The response ratewas 98.2%, the
      majority (68.1%) of the respondents being aged 31-50 years and married. The
      prevalence of screeningamong the respondents over the past 3 years was 27.2%.
      Using a p-value of 0.05 as the significance level, the finalmodel showed that
      marital status (p=0.004), knowledge (p=0.035), perceived barriers (p=0.003), and
      having a regularhealth care provider (p<0.001) were the only significant
      predicting factors of uptake of cervical screening among Africanimmigrant women
      in Klang Valley, Malaysia. Conclusion: The findings revealed that the uptake of
      cervical cancerscreening among the African women was very low. Marital status,
      knowledge, perceived barriers and having a regularhealth care provider were the
      predictive factors. Specific awareness programs to increase uptake should be
      designed andimplemented by the relevant authorities.

PMID- 29582642
TI  - Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative
      Breast Cancer Cells
AB  - Despite a discovery of hormonal pathways regulating breast cancer, a definitive
      cure for the disease requires furtheridentification of alternative targets that
      provide a hormone-independent support. Apart from their role in
      inflammatorydiseases, cysteinyl leukotriene (CysLT) receptor antagonists (LTRAs)
      decrease the risk of lung cancer in asthma patientsand inhibit tumor progression
      in several malignancies. In the present study, we evaluate the effects of two
      chemicallydifferent, clinically relevant LTRAs (montelukast and zafirlukast) in a
      triple negative breast cancer cell line, MDAMB-231. We found that these two LTRAs
      reduced breast cancer cell viability in a dose-dependent manner with the50%
      inhibitory concentration (IC50) between 5-10 MUM. Although both LTRAs have
      several pharmacological propertiesin common, we noticed that montelukast mainly
      induced apoptosis, while zafirlukast mainly exerted its action on cellcycle.
      However, the precise mechanisms responsible for such different effects remain
      unclear. In summary, our resultssuggest that CysLT plays a role in proliferation
      and survivability of breast cancer cells in the absence of hormonal stimuli.

PMID- 29582643
TI  - Chemopreventive Effects of Edible Canna (Canna edulis Kerr.) Against Colorectal
      Carcinogenesis: Effects on Expression of Adenomatous Polyposis Coli and Inducible
      Nitric Oxide Synthase in Rat Inflammatory Model
AB  - Objective: Dietary high fibre and calcium intake has been suggested to reduce
      colorectal cancer risk. However, thereis limited information available regarding
      the potential of edible canna (Ganyong), with high dietary fibre and
      calciumcontent, to act as a preventive agent for colorectal cancer. This
      experimental study was conducted to investigate thepreventive effect of Ganyong
      in reducing colorectal carcinogenesis with attention to effects on adenomatous
      polyposiscoli (APC) and inducible nitric oxide synthase (iNOS) expression.
      Methods: Thirty male Wistar rats were dividedinto 5 equal groups; a normal
      control group without azoxymethane/dextran sodium sulphate (AOM/DSS) inductionand
      Ganyong, a 'cancer' control group with AOM/DSS induction only, and three
      treatment groups with AOM/DSSinduction and different percentages (5%, 10% and
      20%) of Ganyong. Paraffin-embedded sections of rat colon tissuewere analysed by
      haematoxylin-eosin and immunohistochemical staining against antibodies against
      APC and iNOS.Variation in rates of APC and iNOS expression were analyzed using
      the Kruskal-Wallis test followed by the Dunn'stest (SPSS statistic version 24).
      P<0.05 was considered statistically significant. Results: AOM/DSS induction
      increasedthe expression of APC (p=0.013) and iNOS (p=0.013) compared to the
      normal control group. APC expression in thetreated groups was lower than in the
      'cancer' control group (p=0.049), especially in the 10% Ganyong group (p=0.02).In
      contrast, there was no significant variation among the treated groups regarding
      iNOS expression. Histopathologicalfeatures of the colon supported the data for
      APC and iNOS expression. Conclusion: This study indicated
      potentialchemopreventive effects of Ganyong reducing expression of factors
      contributing to colorectal carcinogenesis.

PMID- 29582645
TI  - Quality of Breast Cancer Surgical Pathology Reports
AB  - Background: Surgical pathology reporting of breast cancer is needed for
      appropriate staging and treatment decisions.We here checked the quality of
      surgical pathology reports of breast cancer from different laboratories of
      Karachi,Pakistan. Methods: One hundred surgical pathology reports from ten
      different laboratories of Karachi were assessedfor documentation of elements
      against a checklist adopted from the CAP guideline over a period of six months
      fromJanuary, 2017 to June, 2017 in the Oncology Department, Jinnah Postgraduate
      Medical Centre, Karachi. Results: Outof 100 reports, clinical information was
      documented in 68%, type of procedure and lymph node sampling in 84%and 34%
      respectively. Specimen laterality was mentioned in 90%, tumor site in 44%, tumor
      size in 92%, focality in40%, histological type in 96%, grade in 87%, LCIS in 19%,
      DCIS in 83%, size of DCIS in 19%, architectural patternin 26% , nuclear grade in
      17%, necrosis in 14%, excision margin status in 91%, invasive component in 83%,
      DCIS in16%, lymph node status in 91% with positive nodes in 56%, size of macro
      met in 54%, extranodal involvement in 48%,lymph vascular invasion in 86%,
      treatment effects in 31%, and pathology reporting with TNM in 57%.
      Conclusion:This study shows that the quality of surgical pathology reports for
      breast cancer in Karachi is not satisfactory. Therefore,there is great need to
      create awareness among histopathologists regarding the importance of accurate
      breast cancersurgical pathology reporting and to introduce a standardized
      checklist according to international guidelines for bettertreatment planning.

PMID- 29582644
TI  - Nasopharyngeal Carcinoma Protein Interaction Mapping Analysis via Proteomic
      Approaches
AB  - Nasopharyngeal carcinoma (NPC), although not very common in many parts of the
      world, is a major concern insome countries, including Iran. Molecular studies are
      very helpful to provide essential information regarding underlyingcarcinogenetic
      mechanisms. Here, considering NPC proteomic approaches, established biomarkers
      were designated forprotein-protein interaction network construction and analysis
      with corresponding plug-ins. A network of reported proteinmarkers was constructed
      and topological and biological process features were investigated. Centrality
      analysis showedthat JUN, CALM1, HSB1, and SOD1 are more important than other
      differentially expressed proteins in an interactingpattern. What is more, by
      extending the network, Tp53, PRDM10, AKT1, ALB, HSP90AA1, and EGFR achieved
      thehighest values for NPC network strength. It can be concluded that these
      proteins as well as their contributing processes,particularly in a second
      network, may be important for NPC onset and development. Targeting these
      candidate proteinsmay allow novel treatment approaches following appropriate
      validation.

PMID- 29582646
TI  - A Germline Mutation in the BRCA1 3'UTR Variant Predicts Susceptibility to Breast
      Cancer in a Saudi Arabian Population
AB  - Purpose: The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression and
      altered responses to externalstimuli was previously tested in vitro using a
      luciferase reporter assay. Its ability to predict breast cancer risk in womenwas
      also assessed but the conclusions were inconsistent. The present study concerns
      the relationship between theBRCA1-3'UTR germline variant rs8176318G>T and
      susceptibility to Breast cancer in an ethnic population of SaudiArabia.
      Methodology: The study included 100 breast cancer patients and 100 sex matched
      healthy controls fromthe northwestern region (Tabuk) and Dammam of Saudi Arabia
      were investigated for the BRCA1-3'UTR germlinevariant rs8176318G>T using an
      allele specific PCR technique. Genotype distributions were then compared.
      Results:The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian
      patients were 26%, 8% and 66% andin healthy controls were 45%, 5% and 50%,
      respectively (p=0.03). Risk of developing breast cancer was found to
      besignificantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47,
      1.11-1.93; P=0.007), GT+TT (OR, 2.32,1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and
      the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). Therewere 2.76
      and 2.28 fold increase risks of developing breast cancer associated with the TT
      and GT genotypes in ourcases. A significant correlation was also found between
      the BRCA1 3'UTR variants with the stage of the disease anddistant metastasis but
      not with age, grade, and ER, PR and her2/neu status. Conclusion : The
      rs8176318G/T in the3'untranslated region (UTR) of the BRCA1 gene was found to be
      associatedwith increased susceptibility to breastcancer in our study population,
      increased risk being noted with the GT and TT genotypes. Further association
      studiesare needed to confirm this finding in other regions of Saudi Arabia.

PMID- 29582648
TI  - Defected and Functionalized Germanene-based Nanosensors under Sulfur Comprising
      Gas Exposure.
AB  - Efficient sensing of sulfur containing toxic gases like H2S and SO2 is of the
      utmost importance due to the adverse effects of these noxious gases. Absence of
      an efficient 2D-based nanosensor capable of anchoring H2S and SO2 with feasible
      binding and an apparent variation in electronic properties upon the exposure of
      gas molecules has motivated us to explore the promise of a germanene nanosheet
      (Ge-NS) for this purpose. In the present study, we have performed a comprehensive
      computational investigation by means of DFT-based first-principles calculations
      to envisage the structural, electronic, and gas sensing properties of pristine,
      defected, and metal substituted Ge-NSs. Our initial screening has revealed that
      although interaction of SO2 with pristine Ge-NSs is within the desirable range,
      H2S binding however falls below the required values to guarantee an effective
      sensing. To improve the binding characteristics, we have considered the
      interactions between H2S and SO2 with defected and metal substituted Ge-NS. The
      systematic removals of Ge atoms from a reasonably large super cell lead to
      monovacancy, divacancies, and trivacancies in Ge-NS. Similarly, different
      transition metals like As, Co, Cu, Fe, Ga, Ge, Ni, and Zn have been substituted
      into the monolayer to realize substituted Ge-NS. Our van der Waals corrected DFT
      calculations have concluded that the vacancy and substitution defects not only
      improve the binding characteristics but also enhance the sensing propensity of
      both H2S and SO2. The total and projected density of states show significant
      variations in electronic properties of pristine and defected Ge-NSs before and
      after the exposure to the gases, which are essential in constituting a signal to
      be detected by the external circuit of the sensor. We strongly believe that our
      present work would not only advance the knowledge towards the application of Ge
      NS-based sensing but also provide motivation for the synthesis of such efficient
      nanosensor for H2S and SO2 based on Ge monolayer.

PMID- 29582647
TI  - Differential Expression of c-fos Proto-Oncogene in Normal Oral Mucosa versus
      Squamous Cell Carcinoma
AB  - Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form
      the transcription factor AP-1complex which participates in signal transduction
      and regulation of normal cellular processes. In tumorigenesis, c-Fospromotes
      invasive growth through down-regulation of tumor suppressor genes but its role in
      oral carcinogenesis is notclear. Objectives: This study concerned c-fos gene
      expression in normal and malignant tissues of the oral cavity, withattention to
      associations between expression status and clinico-pathological profiles of OSCC
      patients. Method: A totalof 65 histopathologically confirmed OSCC tissue samples
      were included in case group along with an equal number ofage and sex-matched
      normal tissue samples of oral cavity for the control group. c-Fos protein and m
      RNA expressionswere analyzed using immunohistochemistry and qRT-PCR,
      respectively. Results: A significant low expression of c-Fosprotein was observed
      in OSCC cases than normal control subjects (p= <0.001). The mean percent
      positivity of c-Fosprotein in cases vs. controls was 24.91+/- 2.7 vs. 49.68+/-
      2.2 (p= <0.001). Most OSCC tissue samples showed weak ormoderate c-Fos expression
      whereas 53.8% of normal tissue sections presented with strong immunostaining.
      Moreover,the relative m-RNA expression for the c-fos gene was significantly
      decreased in case group (0.93+/- 0.48) as compared tothe control group (1.22+/-
      0.87). Majority of c-Fos positive cases were diagnosed with well developed tumor.
      The meanpercent positivity of c-Fos protein was significantly lower in higher
      grade tumor as compared with normal oral mucosa(p= < 0.001). Conclusion: The
      present study suggested that the c-fos gene is downregulated in oral carcinomas.
      Thedisparity of c-Fos protein levels in different pathological grades of tumor
      and normal oral tissue samples may indicatethat loss of c-Fos expression is
      related with the progression of OSCC.

PMID- 29582649
TI  - Highly Stretchable, Weavable, and Washable Piezoresistive Microfiber Sensors.
AB  - A key challenge in electronic textiles is to develop an intrinsically conductive
      thread of sufficient robustness and sensitivity. Here, we demonstrate an
      elastomeric functionalized microfiber sensor suitable for smart textile and
      wearable electronics. Unlike conventional conductive threads, our microfiber is
      highly flexible and stretchable up to 120% strain and possesses excellent
      piezoresistive characteristics. The microfiber is functionalized by enclosing a
      conductive liquid metallic alloy within the elastomeric microtube. This
      embodiment allows shape reconfigurability and robustness, while maintaining an
      excellent electrical conductivity of 3.27 +/- 0.08 MS/m. By producing microfibers
      the size of cotton threads (160 MUm in diameter), a plurality of stretchable
      tubular elastic piezoresistive microfibers may be woven seamlessly into a fabric
      to determine the force location and directionality. As a proof of concept, the
      conductive microfibers woven into a fabric glove were used to obtain
      physiological measurements from the wrist, elbow pit, and less accessible body
      parts, such as the neck and foot instep. Importantly, the elastomeric layer
      protects the sensing element from degradation. Experiments showed that our
      microfibers suffered minimal electrical drift even after repeated stretching and
      machine washing. These advantages highlight the unique propositions of our
      wearable electronics for flexible display, electronic textile, soft robotics, and
      consumer healthcare applications.

PMID- 29582650
TI  - Mystery of Cholesterol-Lowering Peptides, Lactostatin and Soystatin.

PMID- 29582651
TI  - Wheat Starch with Low Retrogradation Properties Produced by Modification of the
      GtfB Enzyme 4,6-alpha-Glucanotransferase from Streptococcus thermophilus.
AB  - A GtfB enzyme 4,6-alpha-glucanotransferase from Streptococcus thermophilus
      lacking 761 N-terminal amino acids was heterologously expressed in Escherichia
      coli. Purified S. thermophilus GtfB showed transglycosylation activities toward
      starch, resulting in branch points of (alpha1->6)-glycosidic linkages plus linear
      chains of (alpha1->4)-glycosidic linkages. After wheat starch was modified at a
      rate of 0.1 g/mL by 1-4 U/g starch GtfB at pH 6.0 and 40  degrees C for 1 h, the
      weight-averaged molecular weight decreased from 1.70 * 107 g/mol to 1.21 * 106 to
      3.41 * 106 g/mol, the amylose content decreased from 22.07 to 16.34-17.11%, and
      that of amylopectin long-branch chains decreased from 26.4 to 10.25-15.64% ( P <
      0.05). After the GtfB-modified wheat starches were gelatinized and stored at 4 
      degrees C for 1-2 weeks, their endothermic enthalpies were significantly lower
      than that of the control sample ( P < 0.05), indicating low retrogradation rates.

PMID- 29582652
TI  - In Vivo Quantitative Monitoring of Subunit Stoichiometry for Metabolic Complexes.
AB  - Metabolic pathways often employ assemblies of individual enzymes to facilitate
      substrate channeling to improve thermodynamic efficiency and confer pathway
      directionality. It is often assumed that subunits to multienzyme complexes are
      coregulated and accumulate at fixed levels in vivo, reflecting complex
      stoichiometry. Such assumptions can be experimentally tested using modern tandem
      mass spectrometry, and herein we describe such an approach applied toward an
      important metabolic complex. The committed step of de novo fatty acid synthesis
      in the plastids of most plants is catalyzed by the multienzyme, heteromeric
      acetyl-CoA carboxylase (hetACCase). This complex is composed of four catalytic
      subunits and a recently discovered regulatory subunit resembling the biotin
      carboxyl carrier protein but lacking the biotinylation motif necessary for
      activity. To better understand this novel form of regulation, a targeted tandem
      mass-spectrometry-based assay was developed to absolutely quantify all subunits
      to the Arabidopsis thaliana hetACCase. After validation against pure, recombinant
      protein, this multiplexed assay was used to quantify hetACCase subunits in
      siliques in various stages of development. Quantitation provided a developmental
      profile of hetACCase and BADC protein expression that supports a recently
      proposed regulatory mechanism for hetACCase and demonstrates a promising
      application of targeted mass spectrometry for in vivo analysis of protein
      complexes.

PMID- 29582653
TI  - Oxidative Rearrangement of Secondary Amines Using Hypervalent Iodine(III)
      Reagent.
AB  - A hypervalent iodine(III) reagent mediated oxidative skeletal rearrangement
      reaction of secondary amines is reported. The transformation, which uses
      PhI(OAc)2 in CF3CH2OH, was found to be highly efficient at inducing the direct
      1,2-C-to-N migration of secondary amines. This method offers facile and divergent
      access to polycyclic and macrocyclic indole-fused compounds. The synthetic
      potential of the method is also demonstrated through its application to several
      substrates, including secondary as well as primary amines.

PMID- 29582655
TI  - In Situ Pt Staining Method for Simple, Stable, and Sensitive Pressure-Based
      Bioassays.
AB  - Pressure-based bioassays (PASS) integrate a molecular recognition process with a
      catalyzed gas generation reaction, enabling sensitive and portable quantitation
      of biomarkers in clinical samples. Using platinum nanoparticles (PtNPs) as a
      catalyst has significantly improved the sensitivity of PASS compared with protein
      enzyme-based detection. However, PtNPs are easily deactivated during storage or
      after being decorated with antibodies. Moreover, nonspecific adsorption of PtNPs
      on substrates has been a problem, resulting in significant backgrounds. To solve
      these problems of PtNP-based detection, we report a robust, simple, stable, and
      sensitive Pt staining method for PASS. Detection antibody-decorated gold
      nanoparticles (AuNPs) are used to perform enzyme-linked immunosorbent assay,
      followed by Pt staining to stain AuNPs with Ag and Pt bimetallic shells
      (Au@AgPtNPs), which endow AuNPs with catalytic activity. The concentration of
      targets can be quantitatively determined by measuring the pressure due to O2 gas
      (g) formed by the decomposition of H2O2 catalyzed by Au@AgPtNPs. C-reactive
      protein and avian influenza hemagglutinin 5 neuraminidase 1 can be quantitatively
      detected with detection limits of 0.015 and 0.065 ng/mL, respectively. The
      simple, stable, and sensitive properties of the Pt staining-based method will
      largely broaden the applications of PASS in clinical diagnosis and biomedicine.

PMID- 29582654
TI  - Optically Triggered Planarization of Boryl-Substituted Phenoxazine: Another
      Horizon of TADF Molecules and High-Performance OLEDs.
AB  - We report the unprecedented dual properties of excited-state structural
      planarization and thermally activated delayed fluorescence (TADF) of 10
      dimesitylboryl phenoxazine, i.e., PXZBM. Bearing a nonplanar phenoxazine moiety,
      PXZBM shows the lowest lying absorption onset at ~390 nm in nonpolar solvents
      such as cyclohexane but reveals an anomalously large Stokes-shifted (~14 500 cm
      1) emission maximized at 595 nm. In sharp contrast, when a phenylene spacer is
      added between phenoxazine and dimesitylboryl moieties of PXZBM, the 10-(4
      dimesitylborylphenyl)phenoxazine PXZPBM in cyclohexane reveals a much blue
      shifted emission at 470 nm despite its red-shifted absorption maximized at 420 nm
      (cf. PXZBM). The emission of PXZBM further reveals solvent polarity dependence,
      being red-shifted from 595 nm in cyclohexane to 645 nm in CH2Cl2. For
      rationalization, the steric hindrance between phenoxazine and the dimesitylboryl
      unit in PXZBM caused a puckered arrangement of phenoxazine at the ground state.
      Upon electronic excitation, as supported by the femtosecond early relaxation
      dynamics, spectral-temporal evolution and energetics calculated along the
      reaction potential energy surfaces, the diminution of N -> B electron transfer
      reduces pi-conjugation and elongates the N-B bond length, inducing the fast
      phenoxazine planarization with a time constant of 890 +/- 100 fs. The associated
      charge-transfer reaction from phenoxazine (donor) to dimesitylboryl unit
      (acceptor) results in a further red-shifted emission in polar solvents. In stark
      contrast, PXZPBM shows a planar phenoxazine and undergoes excited-state charge
      transfer only. Despite the distinct difference in excited-state relaxation
      dynamics, both PXZBM and PXZPBM exhibit efficient TADF capable of producing
      highly efficient orange and green organic light emitting diodes with peak
      efficiencies of 10.9% (30.3 cd A-1 and 18.7 lm W-1) and 22.6% (67.7 cd A-1 and
      50.0 lm W-1).

PMID- 29582656
TI  - Modeling the Transport of the "New-Horizon" Reduced Graphene Oxide-Metal Oxide
      Nanohybrids in Water-Saturated Porous Media.
AB  - Little is known about the fate and transport of the "new-horizon" multifunctional
      nanohybrids in the environment. Saturated sand-packed column experiments ( n =
      66) were therefore performed to investigate the transport and retention of
      reduced graphene oxide (RGO)-metal oxide (Fe3O4, TiO2, and ZnO) nanohybrids under
      environmentally relevant conditions (mono- and divalent electrolytes and natural
      organic matter). Classical colloid science principles (Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory and colloid filtration theory (CFT)) and mathematical
      models based on the one-dimensional convection-dispersion equation were employed
      to describe and predict the mobility of RGO-Fe3O4, RGO-TiO2, and RGO-ZnO
      nanohybrids in porous media. Results indicate that the mobility of the three
      nanohybrids under varying experimental conditions is overall explainable by DLVO
      theory and CFT. Numerical simulations suggest that the one-site kinetic retention
      model (OSKRM) considering both time- and depth-dependent retention accurately
      approximated the breakthrough curves (BTCs) and retention profiles (RPs) of the
      nanohybrids concurrently; whereas, others (e.g., two-site retention model) failed
      to capture the BTCs and/or RPs. This is primarily because blocking BTCs and
      exponential/hyperexponential/uniform RPs occurred, which is within the framework
      of OSKRM featuring time- (for kinetic Langmuirian blocking) and depth-dependent
      (for exponential/hyperexponential/uniform) retention kinetics. Employing fitted
      parameters (maximum solid-phase retention capacity: Smax = 0.0406-3.06 cm3/g; and
      first-order attachment rate coefficient: ka = 0.133-20.6 min-1) extracted from
      the OSKRM and environmentally representative physical variables (flow velocity
      (0.00441-4.41 cm/min), porosity (0.24-0.54), and grain size (210-810 MUm)) as
      initial input conditions, the long-distance transport scenarios (in 500 cm long
      sand columns) of the three nanohybrids were predicted via forward simulation. Our
      findings address the existing knowledge gap regarding the impact of
      physicochemical factors on the transport of the next-generation, multifunctional
      RGO-metal oxide nanohybrids in the subsurface.

PMID- 29582657
TI  - Stabilization of Lipase in Polymerized High Internal Phase Emulsions.
AB  - Candida antarctica lipase B is stabilized in a porous, high internal phase
      emulsion (HIPE) of polydicyclopentadiene to enable biocatalytic waste stream
      upcycling. The immobilized lipase is subjected to thorough washing conditions and
      tested for stability in extreme environments and reusability. A porous internal
      microstructure is revealed through scanning electron microscopy. After
      preparation, lipase activity increased to 139 +/- 9.7% of its original activity.
      After 10 cycles of reuse, immobilized lipase retains over 50% activity.
      Immobilized lipase retains activity after 24 h of exposure to temperatures
      ranging from 20 to 60  degrees C and pH values of 3, 7, and 10. In the most
      extreme environments tested, lipase retained 42.8 +/- 21% relative activity after
      exposure to 60  degrees C and 49.4 +/- 16% relative activity after exposure to pH
      3. Polymerized HIPEs stabilize lipase and, thus, extend its working range.
      Further synthesis optimization has the potential to increase enzyme stability,
      immobilization efficiency, and uniformity. The reported hierarchical
      stabilization technique shows promise for use of immobilized lipase in non-ideal,
      industrially relevant conditions.

PMID- 29582658
TI  - Surface Behavior of BSA/Water/Carbohydrate Systems from Molecular Polarizability
      Measurements.
AB  - The effect of the presence of glucose and sucrose on the nonintrinsic
      contribution to partial molar volume ?Theta?ni of bovine serum albumin (BSA) is
      determined by means of static and dynamic electronic polarizability measurements.
      For that aim, a combined strategy based on high-resolution refractometry, high
      exactitude densitometry, and synchronous fluorescence spectroscopy is applied.
      Both static and dynamic mean electronic molecular polarizability values are found
      to be sensitive to the presence of glucose. In the case of sucrose, the
      polarizability of BSA is not appreciably affected. In fact, our results revealed
      that the electronic changes observed occurred without a modification of the
      native conformation of BSA. On the contrary, a nonmonotonous behavior with the
      concentration is observed in presence of glucose. These results advocate the
      influence of the electronic polarization on the repulsive and attractive protein
      carbohydrate interactions. An analysis using the scaled particle theory indicates
      that the accumulation of glucose on the protein surface promotes dehydration.
      Inversely, hydration and preferential exclusion occur in the vicinity of the
      protein surface for sucrose-enriched systems.

PMID- 29582659
TI  - Cigarillo and Little Cigar Mainstream Smoke Constituents from Replicated Human
      Smoking.
AB  - Little cigar and cigarillo smoking is increasing in popularity in the U.S., but
      little is known about the topography and mainstream smoke (MSS) constituents of
      these types of cigar products. This report describes the quantity of selected MSS
      toxicants generated from puff-by-puff replication of human laboratory smoking.
      Participants were dual users of cigarettes and either little cigars ( n = 21) or
      cigarillos ( n = 23). In the laboratory smoking session, participants of the
      little cigar group smoked a filtered unflavored Winchester Little Cigar; those in
      the cigarillo group smoked an unfiltered, unflavored Black & Mild cigarillo. MSS
      components included both volatiles and semivolatile compounds. The MSS of five
      representative U.S. domestic cigarettes was generated using smoking topography
      profiles of the participants smoking their own brand of cigarettes. Machine
      smoking accurately replicated individual puff profiles as indicated by a high
      correlation between lab and machine smoked: time to smoke, number of puffs, and
      total puff volume. There was wide variability in smoking patterns across subjects
      of both little cigars and cigarillos. For example, total puff volume ranged from
      84 to 732 mL after the little cigar and from 270 to 2089 mL after the cigarillo.
      Qualitatively, cigar smoke from little cigars and cigarillos were similar and
      resembles cigarette smoke. All analytes (VOC and SVOCs) were greater in cigarillo
      smoke compared to that of little cigars and cigarettes. However, when the
      toxicants were adjusted for grams of tobacco burned, little cigar smoke contained
      more nicotine, tobacco-specific nitrosamines, acetonitrile, and acrylonitrile
      compared with cigarillo smoke. When the constituents were adjusted for nicotine
      content, cigarillo MSS contained more of all toxicants compared with little
      cigar. Cigarillos and little cigars, like cigarettes, deliver nicotine and other
      toxicants known to be harmful to health; their regulation by the FDA is
      appropriate for their public health risk.

PMID- 29582660
TI  - Occurrence of Single- and Double-Peaked Emission Profiles of Synthetic Chemicals.
AB  - This work aims to elucidate the circumstances that can lead to two peaks in the
      temporal emission profile of synthetic chemicals. Using a simplified substance
      flow model, we explore how emission factors, product lifespan, and degradation
      half-life in waste stock influence the (i) relative importance of emissions from
      three lifecycle stages (industrial processes, use phase, and waste disposal), and
      (ii) the resulting composite emission profile. A double-peaked emission profile
      occurs if the lifespan of products containing the chemical is longer than its
      production history, and the gross emission factor from waste disposal exceeds
      that from the use phase. Since most chemicals fail to meet these two conditions,
      it is reasonable to use single-peaked emission profile as the default in
      environmental studies. On the basis of their emission profiles and contributions
      from individual lifecycle stages, we can categorize chemicals into "simple single
      peakers", "composite single-peakers", and "double-peakers". Our simplified model
      derived emission profiles for five real chemicals that agree well with earlier,
      more sophisticated calculations, indicating the model's ability to capture the
      essential features of actual emissions. It is hoped that the model and
      conclusions in this work will benefit both environmental modelers and decision
      makers.

PMID- 29582662
TI  - Correction to "Glycosyl Bunte-Salts: A Class of Intermediates for Sugar
      Chemistry".

PMID- 29582661
TI  - Rhodium(III)-Catalyzed Imidoyl C-H Activation for Annulations to
      Azolopyrimidines.
AB  - Azolopyrimidines are efficiently prepared by direct imidoyl C-H bond activation.
      Annulations of N-azolo imines with sulfoxonium ylides and diazoketones under
      redox-neutral conditions and alkynes under oxidizing conditions provide products
      with various arrangements of nitrogen atoms and carbon substituents. We have also
      probed the mechanism of this first example of Rh(III)-catalyzed direct imidoyl C
      H activation by structural characterization of a catalytically competent
      rhodacycle obtained after C-H activation and by kinetic isotope effects.

PMID- 29582663
TI  - Topological Phase Transition with Nanoscale Inhomogeneity in (Bi1- xIn x)2Se3.
AB  - Topological insulators are a class of band insulators with nontrivial topology, a
      result of band inversion due to the strong spin-orbit coupling. The transition
      between topological and normal insulator can be realized by tuning the spin-orbit
      coupling strength and has been observed experimentally. However, the impact of
      chemical disorders on the topological phase transition was not addressed in
      previous studies. Herein, we report a systematic scanning tunneling
      microscopy/spectroscopy and first-principles study of the topological phase
      transition in single crystals of In-doped Bi2Se3. Surprisingly, no band gap
      closure was observed across the transition. Furthermore, our spectroscopic
      imaging results reveal that In defects are extremely effective "suppressors" of
      the band inversion, which leads to microscopic phase separation of topological
      insulator-like and normal-insulator-like nano regions across the "transition".
      The observed topological electronic inhomogeneity demonstrates the significant
      impact of chemical disorders in topological materials, shedding new light on the
      fundamental understanding of topological phase transition.

PMID- 29582664
TI  - Microhydration of Dibenzo-18-Crown-6 Complexes with K+, Rb+, and Cs+ Investigated
      by Cold UV and IR Spectroscopy in the Gas Phase.
AB  - In this Article, we examine the hydration structure of dibenzo-18-crown-6
      (DB18C6) complexes with K+, Rb+, and Cs+ ion in the gas phase. We measure well
      resolved UV photodissociation (UVPD) spectra of K+.DB18C6.(H2O) n,
      Rb+.DB18C6.(H2O) n, and Cs+.DB18C6.(H2O) n ( n = 1-8) complexes in a cold, 22
      pole ion trap. We also measure IR-UV double-resonance spectra of the
      Rb+.DB18C6.(H2O)1-5 and the Cs+.DB18C6.(H2O)3 complexes. The structure of the
      hydrated complexes is determined or tentatively proposed on the basis of the UV
      and IR spectra with the aid of quantum chemical calculations. Bare complexes
      (K+.DB18C6, Rb+.DB18C6, and Cs+.DB18C6) have a similar boat-type conformation,
      but the distance between the metal ions and the DB18C6 cavity increases with
      increasing ion size from K+ to Cs+. Although the structural difference of the
      bare complexes is small, it highly affects the manner in which each is hydrated.
      For the hydrated K+.DB18C6 complexes, water molecules bind on both sides (top and
      bottom) of the boat-type K+.DB18C6 conformer, while hydration occurs only on top
      of the Rb+.DB18C6 and Cs+.DB18C6 complexes. On the basis of our analysis of the
      hydration manner of the gas-phase complexes, we propose that, for Rb+.DB18C6 and
      Cs+.DB18C6 complexes in aqueous solution, water molecules will preferentially
      bind on top of the boat conformers because of the displaced position of the metal
      ions relative to DB18C6. In contrast, the K+.DB18C6 complex can accept H2O
      molecules on both sides of the boat conformation. We also propose that the
      characteristic solvation manner of the K+.DB18C6 complex will contribute
      entropically to its high stability and thus to preferential capture of K+ ion by
      DB18C6 in solution.

PMID- 29582665
TI  - Commiphoratones A and B, Two Sesquiterpene Dimers from Resina Commiphora.
AB  - Two sesquiterpene dimers, commiphoratones A (1) and B (2), were isolated from
      Resina Commiphora. Their structures were elucidated by spectroscopic,
      computational, and crystallographic methods. Compounds 1 and 2 represent an
      unusual pattern of dimerization between two types of sesquiterpenes. Moreover,
      compound 1 has a saddle shape. The plausible biosynthetic pathway for 1 and 2 is
      presented. Bioassay showed that 1 and 2 significantly block lipid metabolism in a
      concentration-dependent manner.

PMID- 29582666
TI  - A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock.
AB  - OBJECTIVE: To review and summarize data on angiotensin II (AT-II), approved by
      the Food and Drug Administration (FDA) in December 2017 to increase blood
      pressure in adults with septic or other distributive shock. DATA SOURCES: A
      PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR
      angiotensin 2) AND (shock) from 1966 to February 2018. STUDY SELECTION AND DATA
      EXTRACTION: A total of 691 citations were reviewed with only relevant clinical
      data extracted. DATA SYNTHESIS: AT-II is a peptide hormone with a multitude of
      physiological effects-namely, vasoconstriction of venous and arterial smooth
      muscle. The priority approval granted by the FDA was secondary to a phase 3 study
      of patients receiving at least 0.2 ug/kg/min of norepinephrine or equivalent for
      vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate
      of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10
      mm Hg. No significant difference was found in death by day 28. CONCLUSIONS: AT-II
      is a newly available vasoactive agent with a novel mechanism for the treatment of
      distributive shock. Further research is needed to define its exact role in
      therapy of shock states, identify patients most likely to benefit, and further
      study its safety profile in critical illness.

PMID- 29582667
TI  - Ultrasound screening for abdominal aortic aneurysm: current practice, challenges
      and controversies.
AB  - The UK screening programme began in 2009, and has now been expanded around the
      UK. Long-term follow-up of the original cohorts continues to demonstrate
      significant benefits for abdominal aortic aneurysm (AAA)-related and all-cause
      mortality , and results from the first 5 years of the formal screening programme
      have demonstrated similar success. Ultrasound scanning is an effective and safe
      screening tool for the detection of AAA, although a variety of measurement
      protocols are employed internationally. Key challenges for the future of the
      programme relate to declining incidence of screen detected aneurysms.  Recent
      publications have demonstrated a UK incidence of only 1.34%, compared to 4.9-7.2%
      of men invited for screening in the original trials. Work into increasing
      engagement amongst the target group, and expanding screening to siblings and
      women is underway to address this issue. This review describes the evidence
      behind the screening programme, its justification in addressing AAA as a
      significant health problem and discusses some of the potential developments in
      the future.

PMID- 29582669
TI  - When more is less and less is more: Is there an additional value of NT-proBNP in
      risk stratification in heart failure?

PMID- 29582668
TI  - Robot-Assisted Versus Laparoscopy-Assisted Proximal Gastrectomy for Early Gastric
      Cancer in the Upper Location: Comparison of Oncological Outcomes, Surgical
      Stress, and Nutritional Status.
AB  - BACKGROUND: An increasing amount of attention has been paid to minimally invasive
      function-preserving gastrectomy, with an increase in incidence of early gastric
      cancer in the upper stomach. This study aimed to compare oncological outcomes,
      surgical stress, and nutritional status between robot-assisted proximal
      gastrectomy (RAPG) and laparoscopy-assisted proximal gastrectomy (LAPG). METHODS:
      Eighty-nine patients were enrolled in this retrospective study between November
      2011 and December 2013. Among them, 27 patients underwent RAPG and 62 underwent
      LAPG. Perioperative parameters, surgical stress, nutritional status, disease-free
      survival, and overall survival were compared between the 2 groups. RESULTS: Sex,
      age, and comorbidity were similar in the RAPG and LAPG groups. There were also
      similar perioperative outcomes regarding operation time, complications, and
      length of hospital stay between the groups. The reflux esophagitis rates
      following RAPG and LAPG were 18.5% and 14.5%, respectively ( P = .842). However,
      patients in the RAPG group had less blood loss ( P = .024), more harvested lymph
      nodes ( P = .021), and higher costs than those in the LAPG group ( P < .001).
      With regard to surgical stress, no significant differences were observed in C
      reactive protein concentrations and white blood cell count on postoperative days
      1, 3, and 7 between the groups ( Ps > .05). There appeared to be higher
      hemoglobin levels at 6 months ( P = .053) and a higher body mass index at 12
      months ( P = .056) postoperatively in patients in the RAPG group compared with
      those in the LAPG group, but this difference was not significant. Similar disease
      free survival and overall survival rates were observed between the groups.
      CONCLUSIONS: RAPG could be an alternative to LAPG for patients with early gastric
      cancer in the upper stomach with comparable oncological safety and nutritional
      status. Further well-designed, prospective, large-scale studies are needed to
      validate these results.

PMID- 29582671
TI  - A Standardized Method of Applying Toluidine Blue Metachromatic Staining for
      Assessment of Chondrogenesis.
AB  - Objectives Staining with toluidine blue is a well-established procedure for the
      histological assessment of cartilaginous- and chondrogenic-differentiated
      tissues. Being a cationic dye, toluidine blue staining visualizes proteoglycans
      in a tissue because of its high affinity for the sulfate groups in proteoglycans.
      It is generally accepted that metachromatic staining with toluidine blue
      represents cartilaginous matrix and that the degree of positive staining
      corresponds with the amount of proteoglycans. Design Articular cartilage and
      pellets of chondrocytes or bone marrow stromal cells were analyzed with a
      standardized staining procedure for toluidine blue. Results In the present study,
      we illustrate why such an assumption is invalid unless a detailed description of
      the procedure and/or reference to a detailed published method are provided. This
      is because the staining specificity and intensity depend, as we have shown, on
      the pH of the staining solution, the use of dehydration, and on staining time.
      Conclusions We can, therefore, suggest a well-controlled standardized protocol
      for toluidine blue staining, which provides an easy and simple selective staining
      technique for the assessment of cartilage tissue and proteoglycan development in
      chondrogenic differentiation. If this procedure is not used, then investigators
      must provide sufficient technical information concerning the staining protocol to
      allow an assessment of the validity of the staining results.

PMID- 29582670
TI  - Determining paediatric patient thickness from a single digital radiograph-a proof
      of principle.
AB  - OBJECTIVE: This work presents a proof of principle for a method of estimating the
      thickness of an attenuator from a single radiograph using the image, the exposure
      factors with which it was acquired and a priori knowledge of the characteristics
      of the X-ray unit and detector used for the exposure. It is intended this could
      be developed into a clinical tool to assist with paediatric patient dose audit,
      for which a measurement of patient size is required. METHODS: The proof of
      principle used measured pixel value and effective linear attenuation coefficient
      to estimate the thickness of a Solid Water attenuator. The kerma at the detector
      was estimated using a measurement of pixel value on the image and measured
      detector calibrations. The initial kerma was estimated using a lookup table of
      measured output values. The effective linear attenuation coefficient was measured
      for Solid Water at varying kVp. 11 test images of known and varying thicknesses
      of Solid Water were acquired at 60, 70 and 81 kVp. Estimates of attenuator
      thickness were made using the model and the results compared to the known
      thickness. RESULTS: Estimates of attenuator thickness made using the model
      differed from the known thickness by 3.8 mm (3.2%) on average, with a range of
      0.5-10.8 mm (0.5-9%). CONCLUSION: A proof of principle is presented for a method
      of estimating the thickness of an attenuator using a single radiograph of the
      attenuator. The method has been shown to be accurate using a Solid Water
      attenuator, with a maximum difference between estimated and known attenuator
      thickness of 10.8 mm (9%). The method shows promise as a clinical tool for
      estimating abdominal paediatric patient thickness for paediatric patient dose
      audit, and is only contingent on the type of data routinely collected by Medical
      Physics departments. Advances in knowledge: A computational model has been
      created that is capable of accurately estimating the thickness of a uniform
      attenuator using only the radiographic image, the exposure factors with which it
      was acquired and a priori knowledge of the characteristics of the X-ray unit and
      detector used for the exposure.

PMID- 29582672
TI  - Effect of Hyperbaric Oxygen on Proliferation and Gene Expression of Human
      Chondrocytes: An In Vitro Study.
AB  - Purpose The present study investigated the effects of hyperbaric oxygen (HBO) on
      human chondrocyte proliferation and gene expression patterns. Methods Chondrocyte
      cultures were transferred to a HBO chamber and exposed to 100% oxygen for 7
      consecutive days. Within groups, pressure was varied between 1 and 2 atm and
      duration of HBO administration was varied among 60, 90, and 120 minutes. Cell
      counts were performed using the WST-1 assay at 1, 3, 5, and 7 days after
      initiation of HBO treatment to obtain data to plot a growth curve. Gene
      expression of apoptosis markers PARP and caspase 3, as well as cartilage specific
      proteins collagen II and COMP, were detected by reverse transcription polymerase
      chain reaction. Results The experiments showed that in vitro administration of
      HBO inhibit chondrocyte growth. When applied compression was increased up to 2
      atm, chondrocyte cell count was reduced by half at days 3 and 7 in association
      with an upregulation of the apoptosis markers PARP and caspase 3 as well as the
      cartilage specific proteins collagen II and COMP. No significant differences were
      monitored from varied duration of daily treatment. Conclusion Chondrocyte growth
      was inhibited in vitro by treatment of HBO. This inhibitory effect was even
      increased by elevating the applied pressure, while molecular testing showed
      reduced chondrocyte growth. Higher levels of HBO inhibited cell growth even more,
      but up-regulation of apoptosis specific markers and cartilage specific proteins
      were seen during administration of high oxygen levels. Thus, it has to be
      evaluated that there is a critical level of hypo-/hyperoxia required to stimulate
      or at least maintain chondrocyte cell proliferation.

PMID- 29582673
TI  - Effect of the CCL5-Releasing Fibrin Gel for Intervertebral Disc Regeneration.
AB  - Objective To explore if chemokine (C-C motif) ligand 5 (CCL5) delivery could
      recruit annulus fibrosus (AF) cells to the injury sites and facilitate the repair
      of ruptured AF. Design The effects of CCL5 on bovine AF cells in vitro were
      tested by transwell assay and quantitative real-time polymerase chain reaction.
      Fibrin gel containing CCL5 was used to treat annulotomized bovine caudal discs
      cultured under dynamic loading conditions. After 14 days of loading, the samples
      were collected for histological examination. A pilot animal study was performed
      using sheep cervical discs to investigate the effect of fibrin gel encapsulated
      with CCL5 for the treatment of ruptured AF. After 14 weeks, the animals were
      sacrificed, and the discs were scanned with magnetic resonance imaging before
      histopathological examination. Results CCL5 showed a chemotactic effect on AF
      cells in a dose-dependent manner. AF cells cultured with CCL5 in vitro did not
      show any change of the gene expression of CCL5 receptors, catabolic and
      proinflammatory markers. In vitro release study showed that CCL5 exhibited
      sustained release from the fibrin gel into the culture media; however, in the
      organ culture study CCL5 did not stimulate homing of AF cells toward the defect
      sites. The pilot animal study did not show any repair effect of CCL5. Conclusions
      CCL5 has a chemotactic effect on AF cells in vitro, but no ex vivo or in vivo
      regenerative effect when delivered within fibrin gel. Further study with a
      stronger chemotactic agent and/or an alternate biomaterial that is more
      conductive of cell migration is warranted.

PMID- 29582674
TI  - Current Procedural Terminology Coding for Surgical Pathology: A Review and One
      Academic Center's Experience With Pathologist-Verified Coding.
AB  - CONTEXT.-: The Current Procedural Terminology (CPT) system is a standardized
      numerical coding system for reporting medical procedures and services, and is the
      basis for reimbursement of health care providers by Medicare and other third
      party payers. Accurate CPT coding is therefore crucial for appropriate
      compensation as well as for compliance with Medicare policies, and erroneous
      coding may result in loss of revenues and/or significant monetary penalties for a
      hospital or practice. OBJECTIVE.-: To provide a review of the history, current
      state, and basic principles of CPT coding, in particular as it applies to the
      practice of surgical pathology, and to present our experience with initiating a
      new system of pathologist involvement in the review and verification of CPT
      codes, including the most common codes that require modification in our practice
      at the time of sign-out or post-sign-out auditing. DATA SOURCES.-: Review of
      English language literature, published CPT resources from the American Medical
      Association and other professional organizations, and billing quality data from a
      single institution. CONCLUSIONS.-: Although the appropriate extent of physician
      involvement in CPT coding is a matter of some debate, a multidisciplinary
      approach involving both health care providers and professional coders appears to
      be the best way to achieve accuracy.

PMID- 29582675
TI  - Feasibility of the Less Is More Approach in Treating Low-Risk Ductal Carcinoma In
      Situ Diagnosed on Core Needle Biopsy: Ten-Year Review of Ductal Carcinoma In Situ
      Upgraded to Invasion at Surgery.
AB  - CONTEXT: - Ductal carcinoma in situ (DCIS) represents 20% of screen-detected
      breast cancers. The likelihood that certain types of DCIS are slow growing and
      may never progress to invasion suggests that our current standards of treating
      DCIS could result in overtreatment. The LORIS (LOw RISk DCIS) and LORD (LOw Risk
      DCIS) trials address these concerns by randomizing patients with low-risk DCIS to
      either active surveillance or conventional treatment. OBJECTIVE: - To determine
      the upgrade rate of DCIS diagnosed on core needle biopsy to invasive carcinoma at
      surgery and to evaluate the safety of managing low-risk DCIS with surveillance
      alone, by characterizing the pathologic and clinical features of upgraded cases
      and applying criteria of the LORD and LORIS trials to these cases. DESIGN: - A 10
      year retrospective analysis of DCIS on core needle biopsy with subsequent
      surgery. RESULTS: - We identified 1271 cases of DCIS on core needle biopsy: 200
      (16%) low grade, 649 (51%) intermediate grade, and 422 (33%) high grade. Of the
      1271 cases, we found an 8% upgrade rate to invasive carcinoma (n = 105). Nineteen
      of the 105 upgraded cases (18%) had positive lymph nodes. Low-grade DCIS was
      least likely to upgrade to invasion, comprising 10% (10 of 105) of upgraded
      cases. Three of the 105 upgraded cases (3%) met criteria for the LORD trial, and
      all were low-grade DCIS on core needle biopsy with favorable biology on follow
      up. CONCLUSIONS: - There is a clear risk of upgrade to invasion on follow-up
      excision; however, applying strict criteria of the LORD trial effectively
      decreases the likelihood of a missed invasive component or missed aggressive
      pathologic features.

PMID- 29582676
TI  - Factors Impacting the Performance Characteristics of Bile Duct Brushings: A
      Clinico-Cytopathologic Analysis of 253 Patients.
AB  - CONTEXT: - Literature on factors impacting bile duct brushings (BDBs) performance
      characteristics remain limited. OBJECTIVE: - To capture the current state of
      daily practice with BDB sign-out. DESIGN: - Two hundred fifty-three of 444 BDBs
      signed out by more than 7 cytopathologists, with histopathologic and/or clinical
      follow-up of at least 18 months, were examined. RESULTS: - One hundred thirty
      five of 253 BDBs (53%) had histologically confirmed malignancies, 22 (9%) had
      cancer-related deaths, and 96 (38%) were benign. Cytologic diagnoses in the 444
      BDBs were nondiagnostic (11 [2.5%]), negative (284 [64%]), atypical (62 [13.9%]),
      suspicious (34 [7.7%]), and malignant (53 [11.9%]). Sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV), and accuracy of
      malignancy detection were 35%, 100%, 100%, 58%, and 66%, respectively. When
      atypical, suspicious, and malignant (ASM) categories were combined, sensitivity
      increased (58%), specificity and PPV dropped (97%), and accuracy increased (73%).
      Carcinoma type (bile-duct versus pancreatic-ductal) had no effect on accuracy ( P
      = .60) or diagnostic class ( P = .84), nor did time of performance (first 7.5
      versus latter 7.5 years, P = .13). Interestingly, ThinPrep + cell block (n = 41)
      had higher sensitivity (61%) and lower specificity (80%) than ThinPrep only
      (versus 51% and 100%, respectively). Sensitivity and specificity were higher (47%
      and 100%) in nonstented than stented specimens (59% and 97%). Relative risk of
      malignancy for "suspicious" (2.30) and "atypical" (2.28) categories was lower but
      not very different from that of "malignant" category (2.41). CONCLUSIONS: - Bile
      duct brushings had fairly low sensitivity but high specificity and PPV with no
      false positives. Sensitivity almost doubled and specificity dipped minimally when
      ASM categories were combined, highlighting the need for better classification
      criteria for atypical/suspicious cases. Higher specificity, PPV, NPV, and
      accuracy but lower sensitivity in stented BDBs suggest that they be called
      malignant only when evidence is overwhelmingly convincing.

PMID- 29582677
TI  - Noninvasive Follicular Thyroid Neoplasms With Papillary-like Nuclear Features Are
      Genetically and Biologically Similar to Adenomatous Nodules and Distinct From
      Papillary Thyroid Carcinomas With Extensive Follicular Growth.
AB  - CONTEXT: - Proposed noninvasive follicular thyroid neoplasm with papillary-like
      nuclear features (NIFTPs), formerly noninvasive encapsulated papillary carcinoma,
      follicular variant (PTC-FV), is an indolent tumor with follicular growth and
      frequent RAS mutations. OBJECTIVE: - To detect histologic and molecular
      differences separating NIFTP from follicular adenomas (FAs) and invasive
      carcinomas, particularly papillary carcinomas with extensive follicular growth
      (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV). DESIGN: - Sixty-one
      tumors were reviewed histologically and reclassified into 32 NIFTPs (52%), 4 IE
      PTC-FVs (7%), 14 PTC-EFGs (23%), and 11 FAs (18%). Next-generation sequencing for
      mutations in 50 genes was performed. Clinical outcomes were recorded. RESULTS: -
      The NIFTPs and FAs were well circumscribed and unencapsulated. The FAs had bland
      nuclei, whereas the NIFTPs showed at least 2 of 3 (67%; sufficient) nuclear
      features (enlargement, irregular contours, chromatin clearing). The IE-PTC-FVs
      had follicular growth, sufficient nuclear features, and extensive capsular
      invasion. The PTC-EFGs had a median of 5% papillae with intrathyroidal invasion
      (broad-based, sclerotic, or small follicle growth patterns); intranuclear
      pseudoinclusions were present only in PTC-EFGs (9 of 14; 64%). Mutations included
      RAS in 20 of the 32 NIFTPs (62%), 4 of the 11 FAs (36%), and 3 of the 4 IE-PTC
      FVs (75%); BRAF K601E in 1 NIFTP (3%); BRAF V600E in 5 PTC-EFGs (36%). No NIFTPs
      or FAs recurred or metastasized. All 4 IE-PTC-FVs (100%) had hematogenous
      metastasis. Two PTC-EFGs (14%) had lymphatic metastasis. CONCLUSIONS: - The
      morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports
      the genetic similarity of those follicular neoplasms in contrast to the unique
      presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria
      supported by molecular testing, tumors with extensive follicular growth can be
      classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus
      papillary type or BRAF V600E-like (PTC-EFG).

PMID- 29582678
TI  - Vascular access via translumbar Hemodialysis Reliable Outflow dialysis catheter
      in a case of severe central venous occlusion.

PMID- 29582679
TI  - Does the real-time ultrasound guidance provide safer venipuncture in implantable
      venous port implantation?
AB  - AIM: To examine whether the real-time ultrasound-guided venipuncture for
      implantable venous port placement is safer than the traditional venipuncture.
      METHODS: The study analyzed the results of 2153 venous ports placed consecutively
      from January 2009 to January 2016. A total of 922 patients in group 1 and 1231
      patients in group 2 were admitted with venous port placed using the traditional
      landmark subclavian approach and real-time ultrasound-guided axillary approach,
      respectively. Sociodemographic characteristics of patients, early (pneumothorax,
      pinch-off syndrome, arterial puncture, hematoma, and malposition arrhythmia) and
      late (deep vein thrombosis, obstruction, infection, erosion-dehiscence, and
      rotation of the port chamber) complications and the association of these
      complications with the implantation method were evaluated. RESULTS: There were no
      significant differences in the sociodemographic characteristics of the patients
      between the two groups. The overall and early complications in group 2 were
      significantly lower than those in group 1. Pinch-off syndrome only developed in
      group 1. Seven patients and two patients had pneumothorax in groups 1 and 2,
      respectively. Puncture number was significantly associated with the development
      of the overall complications. CONCLUSION: The ultrasound-guided axillary approach
      may be preferred as a method to reduce the risk of both early and late
      complications. Large, randomized, controlled prospective trials will be helpful
      in determining a safer implantable venous port implantation technique.

PMID- 29582680
TI  - Catheter-related complications and survival among incident hemodialysis patients
      in Singapore.
AB  - INTRODUCTION:: Hemodialysis is the main modality of renal replacement therapy in
      Singapore. However, a majority of the patients in Singapore are initiated on
      hemodialysis via a catheter. This study examines the complication rates and
      factors predicting catheter-related bloodstream infections and mortality rates in
      patients who were initiated on hemodialysis at our institution. METHODS:: This is
      a single-center retrospective analysis of incident hemodialysis patients who were
      initiated on renal replacement therapy between 1 January 2010 and 31 December
      2012. Catheter-related bloodstream infection risk factors, organisms, and
      associated mortality were analyzed. RESULTS:: The catheter-related bloodstream
      infection and exit site infection incidence rates were 0.75 and 0.50 per 1000
      catheter days, respectively. The mean duration to first catheter-related
      bloodstream infection episode was 182.47 +/- 144.04 catheter days. Prolonged
      catheter duration was found to be a risk factor for catheter-related bloodstream
      infection. Compared to patients initiated on dialysis via arteriovenous fistula,
      initiation of dialysis via catheter is strongly associated with increased
      mortality (6.0% vs 14.5%; p = 0.02). In particular, the presence of diabetes
      mellitus and development of catheter-related bloodstream infection was associated
      with increased mortality ( p = 0.04 and 0.05, respectively). In addition,
      patients who began hemodialysis before being seen by a nephrologist were
      associated with decreased mortality (3.4% vs 13.0%; p = 0.03). CONCLUSION:: In
      conclusion, prolonged duration of catheter insertion is found to be a risk factor
      for catheter-related bloodstream infection in hemodialysis patients, and its
      development is associated with increased mortality. Early referral to a
      nephrologist and creation of arteriovenous fistula in pre-end-stage renal disease
      patients are pivotal in improving the outcomes of patients.

PMID- 29582681
TI  - Iodide mumps following vascular access management.

PMID- 29582682
TI  - Mental health needs in forcibly displaced populations: critical reflections.

PMID- 29582683
TI  - Incidence, Risk Factors, and Treatment of Achilles Tendon Rupture in Patients
      With End-Stage Renal Disease.
AB  - BACKGROUND: Dialysis-dependent patients and kidney transplant recipients may be
      at increased risk for Achilles tendon rupture (ATR). METHODS: We studied Medicare
      patients with end-stage renal disease (ESRD) from 1999 through 2013. Patients
      were categorized as waitlisted for a transplant, not waitlisted, or received a
      transplant. We performed multivariate negative binomial regression using
      demographic characteristics, comorbidities, and year of study entry to estimate
      adjusted incidence rate ratios (aIRRs), identify ATR risk factors, and determine
      treatment patterns and outcomes. RESULTS: We identified 1091 ATRs (incidence,
      3.80/10 000 person-years; 95% confidence interval [CI], 3.58-4.03). Compared with
      transplant recipients, nonwaitlisted patients had a lower incidence (aIRR, 0.44;
      95% CI, 0.37-0.53), and waitlisted patients had a similar incidence (aIRR, 0.94;
      95% CI, 0.78-1.12) of ATR. ATR incidence was higher among patients taking
      fluoroquinolones (aIRR, 1.65; 95% CI, 1.32-1.84) and corticosteroids (aIRR, 1.72;
      95% CI, 1.44-2.05) compared with those who did not. Patients with ATR were
      younger, had higher mean body mass index, and had fewer comorbidities than
      patients without ATR. Seventeen percent of patients received operative treatment
      within 14 days of ATR diagnosis. The 30-day cumulative incidence of operative
      site infections was 6.5%. CONCLUSION: The incidence of ATR was higher among
      transplant recipients and waitlisted patients compared with nonwaitlisted
      patients. Younger age, higher body mass index, fewer comorbidities,
      fluoroquinolone use, and corticosteroid use were risk factors for ATR. Patients
      were more likely to receive nonoperative than operative treatment for ATR. Those
      who underwent operative treatment had a low incidence of operative site
      infection. LEVEL OF EVIDENCE: Prognostic level III, comparative study.

PMID- 29582684
TI  - Strength of Interference Screw Fixation to Cuboid vs Pulvertaft Weave to Peroneus
      Brevis for Tibialis Posterior Tendon Transfer for Foot Drop.
AB  - BACKGROUND: Tibialis posterior (TP) tendon transfer is an effective treatment for
      foot drop. Currently, standard practice is to immobilize the ankle in a cast for
      6 weeks nonweightbearing, risking postoperative stiffness. To assess whether
      early active dorsiflexion and protected weightbearing could be safe, the current
      study assessed tendon displacement under cyclic loading and load to failure,
      comparing the Pulvertaft weave (PW) to interference screw fixation (ISF) in a
      cadaveric foot model. METHODS: Twenty-four cadaveric ankles had TP tendon
      transfer performed, 12 with the PW technique and 12 with ISF to the cuboid. The
      TP tendon was cycled 1000 times at 50 to 150 N and then loaded to failure in a
      materials testing machine. Tendon displacement at the insertion site was recorded
      every 100 cycles. An independent t test and 2-way analysis of variance were
      performed to compare techniques, with a significance level of P < .05. RESULTS:
      Mean tendon displacement was similar in the PW group (2.9 +/- 2.5 mm [mean +/-
      SD]) compared with the ISF group (2.4 +/- 1.1 mm), P = .35. One specimen in the
      ISF group failed early by tendon pullout. None of the PW group failed early,
      although displacement of 8.9 mm was observed in 1 specimen. Mean load to failure
      was 419.1 +/- 82.6 N in the PW group in comparison to 499.4 +/- 109.6 N in the
      ISF group, P = .06. CONCLUSION: For TP tendon transfer, ISF and PW techniques
      were comparable, with no differences in tendon displacement after cyclical
      loading or load to failure. Greater variability was observed in the PW group,
      suggesting it may be a less reliable technique. CLINICAL RELEVANCE: The results
      indicate that early active dorsiflexion and protected weightbearing may be safe
      for clinical evaluation, with potential benefits for the patient compared with
      cast immobilization.

PMID- 29582685
TI  - 'Real-life' experience with direct-acting antiviral agents for hepatitis C virus
      in end-stage renal disease.
AB  - BACKGROUND AND AIMS: The advent of direct-acting antiviral agents promises to
      change the management of hepatitis C in patients with end-stage renal disease, a
      patient group where the treatment of hepatitis C was historically challenging. We
      investigated the safety and efficacy of all-oral, interferon-free direct-acting
      antiviral agents for the treatment of hepatitis C in a 'real-world' group of
      patients with end-stage renal disease. METHODS: We performed a single-arm, multi
      centre study in a cohort (n=30) of patients with advanced chronic kidney disease
      (mostly on dialysis) who underwent antiviral therapy with direct-acting antiviral
      agents. The primary end-point was sustained virologic response (serum hepatitis C
      virus RNA < 15 mIU/mL, 12 weeks after treatment ended). We collected data on on
      treatment adverse events, serious adverse events and laboratory abnormalities.
      RESULTS: In total, 23 (77%) and 7 (23%) patients underwent regular dialysis and
      had chronic kidney disease at pre-dialysis stage, respectively. Six regimens were
      adopted: elbasvir/grazoprevir ( n = 6), ledipasvir/sofosbuvir +/- ribavirin ( n =
      4), PrOD regimens +/- ribavirin ( n = 10), simeprevir + daclatasvir ( n = 3),
      sofosbuvir + daclatasvir +/- ribavirin ( n = 3), sofosbuvir + ribavirin ( n = 4).
      The SVR12 rate was 90% (95% confidence interval, 74%; 96%). A total of 27 (90%)
      patients achieved SVR12; there were three virologic failures - two were non
      responders and one had a viral breakthrough while on therapy. Adverse events
      occurred in 53% (16/30) (95% confidence interval, 0.39; 0.73) of patients and
      were managed clinically without discontinuation of therapy or hospitalization.
      The most common adverse event was anaemia ( n = 12) that required blood
      transfusions in seven individuals; deterioration of kidney function occurred in
      one (14%). CONCLUSION: All-oral, interferon-free therapy with direct-acting
      antiviral agents for chronic hepatitis C virus in advanced chronic kidney disease
      was effective and well tolerated in a 'real-life' clinical setting. Careful
      monitoring of haemoglobin and serum creatinine during therapy with direct-acting
      antiviral agents is suggested. Studies are under way to address whether sustained
      viral response translates into better survival in this population.

PMID- 29582686
TI  - The effects of radiotherapy on the survival of patients with unresectable non
      small cell lung cancer.
AB  - INTRODUCTION: Lung cancer represents the leading cause of cancer mortality across
      the worlds. At present, less than 30% of the patients can undergo curative
      surgery, while the majority of them (65%) are diagnosed with metastatic disease
      and directed to systemic treatments. In this context there is a subset of
      patients (25%) with locally advanced stage disease whose outcome might be
      improved by using combined strategies of treatment including chemotherapy,
      radiotherapy and surgery. Areas covered: Here we reviewed possible combination
      strategies aimed to improve the outcome of lung cancer patients, focusing on the
      role of radiotherapy both in the adjuvant and oligo-metastatic setting and in
      synergy with immunotherapy, and finally, we afforded the new challenges
      concerning the advanced RT and precision oncology. We carried out a focused
      analysis concerning the key clinical management weaknesses as well as the
      potential that current research holds. Expert commentary: We believe that the
      most promising clinical trials in this specific patient subset will build their
      rationale on the results of well-designed translational models aimed to test the
      combination of cytotoxic drugs, radiobiology, and immune-pharmacology. In this
      context, remarkable investigational fields are focused on the attempt to combine
      radiotherapy with chemo-immunological strategies and precision medicine
      protocols.

PMID- 29582688
TI  - The politics and practice of Thomas Adeoye Lambo: towards a post-colonial history
      of transcultural psychiatry.
AB  - This article traces the career of Thomas Adeoye Lambo, the first European-trained
      psychiatrist of indigenous Nigerian (Yoruba) background and one of the key
      contributors to the international development of transcultural psychiatry from
      the 1950s to the 1980s. The focus on Lambo provides some political, cultural and
      geographical balance to the broader history of transcultural psychiatry by
      emphasizing the contributions to transcultural psychiatric knowledge that have
      emerged from a particular non-western context. At the same time, an examination
      of Lambo's legacy allows historians to see the limitations of transcultural
      psychiatry's influence over time. Ultimately, this article concludes that the
      history of transcultural psychiatry might have more to tell us about the politics
      of the 'transcultural' than the practice of 'psychiatry' in post-colonial
      contexts.

PMID- 29582687
TI  - Dual method use among long-acting reversible contraceptive users.
AB  - OBJECTIVE: To compare rates of dual method use (concurrent use of condoms and an
      effective method of contraception) in long-acting reversible contraceptive (LARC)
      and non-LARC hormonal contraceptive users, and to determine factors associated
      with dual method use. METHODS: We conducted a secondary analysis of the
      Contraceptive CHOICE Project, an observational, prospective cohort study of 9256
      women in St. Louis, MO, USA. Our sample included 6744 women who initiated a
      contraceptive method within 3 months of enrollment, continued use at 6 months
      post-enrollment, and responded regarding dual method use. Our primary outcome was
      the rate of dual method use at 6 months post-enrollment. RESULTS: Dual method use
      was reported by 32% of LARC and 45% of non-LARC hormonal contraceptive users (p <
      .01). After adjusting for other covariates and comparing to non-LARC hormonal
      contraceptive users, LARC users were less likely to report dual method use (RRadj
      0.76, 95% CI 0.70-0.83). Factors associated with dual method use in our
      multivariable analysis were age <25 years, black race, lower education, single
      relationship status, baseline dual method use, baseline diagnosis of sexually
      transmitted infection (STI), greater partner willingness to use a condom, and
      higher condom self-efficacy score. CONCLUSIONS: LARC users are less likely to
      report dual method use compared to non-LARC hormonal contraceptive users, but
      other factors also impact dual method use. Further studies should be performed to
      determine whether this lower dual method use increases the risk of STI. CLINICAL
      TRIALS REGISTRATION: Clinicaltrials.gov Identifier NCT01986439.

PMID- 29582690
TI  - Olaparib for the treatment of breast cancer.
AB  - INTRODUCTION: Mutations in BRCA1 and BRCA2 genes account for around 2-3% of
      breast cancer events and more than 10% of triple negative breast cancers.
      Olaparib (Lynparza(r)), an orally administered PARP inhibitor, demonstrated
      clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative
      metastatic breast cancer. Areas covered: This review gives an overview of
      available preclinical and clinical data regarding olaparib, including its
      chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and
      evidence supporting antitumor efficacy and safety profile in breast cancer
      patients. Expert commentary: Olaparib improves progression-free survival in
      germline BRCA mutated HER2 negative metastatic breast cancer patients as compared
      to standard chemotherapy, with a manageable toxicity profile. Efficacy is of
      clinical relevance especially in the context of triple negative breast cancer.
      However, several aspects, such as sequencing or combination of these agents with
      other anticancer agents and identification of appropriate biomarkers, still need
      to be clearly defined.

PMID- 29582689
TI  - Metallic materials in the exomass impair cone beam CT voxel values.
AB  - OBJECTIVES: To assess the influence of artefacts arising from metallic materials
      in the exomass on cone beam CT (CBCT) voxel values. METHODS: CBCT scans were
      taken of a phantom composed of 16 tubes filled with a homogeneous hyperdense
      solution and metallic materials of different compositions (titanium, cobalt
      chromium and amalgam) and numbers (one, two and three). The phantom was centred
      in a 5 * 5 cm field of view such that the metallic materials were located in the
      exomass, using three CBCT units. Voxel values were obtained from the 16
      homogeneous areas and averaged. Also, standard deviation was calculated to
      measure voxel value variability. Analysis of variance in a factorial scheme with
      additional treatment 3 * 3 + 3 (material * number + control) was performed,
      followed by Tukey's test for multiple comparisons, and Dunnett's test for
      comparisons with the control groups, at a level of significance of 5%. RESULTS:
      Metallic material in the exomass significantly reduced the mean voxel value in
      the CS9300 and Picasso Trio units, and increased voxel value variability in all
      CBCT units. Amalgam was the material that induced significantly greater reduction
      of the mean voxel value in the CS9300 and Picasso Trio units, and significantly
      greater increase in the NewTom Giano. Voxel value variability was significantly
      greater for amalgam in all conditions. The presence of one cylinder induced
      significantly less pronounced effects on the mean voxel value and voxel value
      variability. CONCLUSIONS: Artefacts arising from metallic materials in the
      exomass have a negative influence on CBCT voxel values.

PMID- 29582691
TI  - Eric Wittkower and the foundation of Montreal's Transcultural Psychiatry Research
      Unit after World War II.
AB  - Eric Wittkower founded McGill University's Transcultural Psychiatry Unit in 1955.
      One year later, he started the first international newsletter in this academic
      field: Transcultural Psychiatry. However, at the beginning of his career
      Wittkower gave no signs that he would be interested in social sciences and
      psychiatry. This paper describes the historical context of the post-war period,
      when Wittkower founded the research unit in Montreal. I focus on the history of
      scientific networks and the circulation of knowledge, and particularly on the
      exchanges between the French- and English-speaking academic cultures in North
      America and Europe. Because the history of transcultural psychiatry is a
      transnational history par excellence, this leads necessarily to the question of
      the reception of this academic field abroad.

PMID- 29582692
TI  - Differential effects of epidermal growth factor (EGF) receptor ligands on
      receptor binding, downstream signalling pathways and DNA synthesis in
      hepatocytes.
AB  - Hepatocytes are responsive to mitogenic effects of several ligands acting via
      EGFR. Studying primary cultures of rat hepatocytes, we found that, as compared to
      EGF, HB-EGF had a markedly higher affinity of the EGFR, while AR and TGFalpha had
      lower affinity. HB-EGF was also more potent compared to the other growth factors
      regarding phosphorylation of EGFR, Shc, ERK1/2 and Akt. All ligands induced
      phosphorylation of ErbB2, indicating receptor heterodimerization. TGFalpha,
      despite having much lower receptor affinity, was about equally potent and
      efficacious as HB-EGF as a stimulator of DNA synthesis. In contrast, EGF had
      relatively high affinity but markedly lower efficacy in stimulation of DNA
      synthesis. The results suggest that amplifying and/or inhibitory mechanisms may
      modulate the mitogenic responses downstream of the initial signalling steps, and
      that this may affect the effects of the EGFR ligands differentially.

PMID- 29582693
TI  - A theoretical analysis and finite element simulation of fixator-bone system
      stiffness on healing progression.
AB  - INTRODUCTION: The unilateral external fixator has become a quick and easy
      application for fracture stabilization of the extremities; the main value for
      evaluation of mechanical stability of the external fixator is stiffness. The
      stiffness property of the external fixator affects the local biomechanical
      environment of fractured bone. METHODS: In this study, a theoretical model with
      changing Young's modulus of the callus is established by using the Castigliano's
      theory, investigating compression stiffness, torsional stiffness and bending
      stiffness of the fixator-bone system during the healing process. The effects of
      pin deviation angle on three stiffness methods are also investigated. In
      addition, finite element simulation is discussed regarding the stress
      distribution between the fixator and bone. RESULTS: The results reveal the three
      stiffness evaluation methods are similar for the fixator-bone system. Finite
      element simulation shows that with increased healing time, the transmission of
      the load between the fixator and bone are different. In addition, the finite
      element analyses verify the conclusions obtained from the theoretical model.
      CONCLUSIONS: This work helps orthopedic doctors to monitor the progression of
      fracture healing and determine the appropriate time for removal of a fixation
      device and provide important theoretical methodology.

PMID- 29582694
TI  - Anconeus Epitrochlearis Muscle Associated With Cubital Tunnel Syndrome: A Case
      Series.
AB  - BACKGROUND: Cubital tunnel syndrome is a common compressive neuropathy of the
      upper extremity. The anconeus epitrochlearis muscle is an unusual but occasional
      contributor. We review our experience with this anomalous muscle in elbows with
      cubital tunnel syndrome. METHODS: We retrospectively reviewed charts of 13
      patients noted to have an anconeus epitrochlearis muscle associated with cubital
      tunnel syndrome. RESULTS: Ten patients had unilateral ulnar neuropathy supported
      by nerve conduction studies. Three had bilateral cubital tunnel syndrome symptoms
      with 1 of those having normal nerve conduction studies for both elbows. Eight
      elbows were treated with myotomy of the anconeus epitrochlearis muscle and
      submuscular transposition of the ulnar nerve. The other 8 elbows were treated
      with myotomy of the anconeus epitrochlearis muscle and in situ decompression of
      the ulnar nerve only. All but 1 patient had either clinical resolution or
      improvement of symptoms at follow-up ranging from 2 weeks to 1 year after
      surgery. The 1 patient who had persistent symptoms had received myotomy and in
      situ decompression of the ulnar nerve only. CONCLUSIONS: An anomalous anconeus
      epitrochlearis occasionally results in compression of the ulnar nerve but is
      usually an incidental finding. Its contribution to compression neuropathy can be
      tested intraoperatively by passively ranging the elbow while observing the change
      in vector and tension of its muscle fibers over the ulnar nerve. Regardless of
      findings, we recommend myotomy of the muscle and in situ decompression of the
      ulnar nerve. Submuscular transposition of the ulnar nerve may be necessary if
      there is subluxation.

PMID- 29582695
TI  - Development of a pressure sensor system for unobtrusive monitoring of abdominal
      muscle activities.
AB  - Surface electromyogram (sEMG) is often used by to objectively measure muscular
      activity during rehabilitation exercises. sEMG is accurate, but it is unsuitable
      for uses outside the clinic, and patients can benefit from an unobtrusive device
      which can be readily used to ubiquitously measure abdominal muscle activation. In
      this study, we present a pressure sensor system which can be latched onto a belt
      to measure abdominal muscle activation. sEMG and pressure sensor output were
      measured in 15 healthy young males during isometric trunk flexion exercise
      (public trials registration number, KCT0002351), and the results were highly
      correlated (median R > 0.939). As initial contact force can change the pressure
      sensor sensitivity, the experiment was performed at two different levels of belt
      tightness, but the correlations did not significantly improve after tightening
      the belt, suggesting that the system can be used to ubiquitously and
      unobtrusively monitor abdominal muscle activity with minimal discomfort.

PMID- 29582696
TI  - Anti-CD38 and anti-SLAMF7: the future of myeloma immunotherapy.
AB  - INTRODUCTION: the high expression of a number of surface antigens on malignant
      plasma cells, the bone marrow micro-environment and immune effector T cells,
      makes these appealing targets for immune therapy with monoclonal antibodies
      (mAbs). Areas covered: Two mAbs, anti-CD38 daratumumab (Dara) and anti-SLAMF7
      elotuzumab (Elo), have achieved recent regulatory approval for relapsed or
      refractory MM (RRMM) and are currently being explored as possible treatment
      options in novel combinations and different settings. This review discusses the
      current landscape and possible development of anti-CD38 and anti-SLAMF7 mAbs.
      Expert commentary: Three phase III trials demonstrated a significant advantage in
      terms of response and PFS when Dara or Elo are combined with lenalidomide
      dexamethsone (Rd) or bortezomib-dexamethsone (Vd), in comparison to doublet
      regimens, for patients with RRMM. Treatment algorithms including Dara- or Elo
      based triplets may be defined on the basis of disease and patients'
      characteristics, as well as of their prior exposure to different classes of novel
      agents. Evaluation of these agents in new combination regimens, including second
      and third generation PIs and IMiDs, are under investigation. Moreover, use of
      mAbs in phases of the disease where the immune system is less compromised, such
      as newly diagnosed MM or even high-risk smoldering myeloma, appears logical.

PMID- 29582697
TI  - Nonhepatosplenic extramedullary manifestations of chronic myelomonocytic
      leukemia: clinical, molecular and prognostic correlates.

PMID- 29582698
TI  - A new category stent with novel polyphosphazene surface modification.
AB  - The COBRA-PzFTM (CeloNova BioSciences, Inc., TX, USA) is a new type of coronary
      stent composed of a cobalt chromium metallic backbone surrounded by a nanothin
      layer of Polyzene-F (PzF) without any added drug. Evidence from basic studies
      supports antithrombotic and anti-inflammatory properties for the PzF surface
      coating. Preclinical studies support the thromboresistance of PzF-coated surfaces
      and clinical studies have shown good outcomes for patients receiving this device
      with very low rates of stent thrombosis. COBRA-PzF may be especially useful in
      patients at high risk for bleeding. Ongoing clinical trials will determine
      whether shortening the duration of dual antiplatelet therapy to less than 1 month
      is feasible and these data may represent a new paradigm with regards to patients
      at high risk for bleeding.

PMID- 29582699
TI  - Strong immunoexpression of dickkopf-1 is associated with response to bortezomib
      in multiple myeloma.
AB  - The predictive significance of osteolysis-related proteins was evaluated in
      bortezomib-treated multiple myeloma. The clinicopathological characteristics were
      collected retrospectively. Immunohistochemistry was performed for analyzing
      receptor activator of NF-kappaB ligand (RANKL), osteoprotegerin (OPG), macrophage
      inflammatory protein 1 alpha (MIP1alpha), and dickkopf-1 (DKK1) expression. Among
      clinicopatholgical characteristics, osteolytic lesion was associated with higher
      response to bortezomib treatment (79% vs. 46%). High DKK1 expression was
      significantly correlated with osteolytic lesion (p = .003), whereas RANKL, OPG,
      and MIP1alpha were not. In high DKK1 expression, higher response to bortezomib
      was observed (84% vs. 44%). In multivariate analysis, high DKK1 expression was
      associated with better response to bortezomib (p = .005). Patients with high DKK1
      expression had longer median progression-free survival (PFS) and overall survival
      (OS) after bortezomib treatment. In multivariate analysis, high DKK1 expression
      was an independent prognostic factor of favorable PFS (p = .027) and OS (p =
      .035). In multiple myeloma treated with bortezomib, expression status of DKK1 may
      be a useful predictive marker.

PMID- 29582700
TI  - Reducing Surgical Revisions in Intracranial Complications of Pediatric Acute
      Sinusitis.
AB  - Objective (1) To describe the demographics and clinical course of children with
      intracranial complications of sinusitis. (2) To elucidate factors that predict
      revision surgery in this population, such as type of initial surgery. Study
      Design Case series with chart review. Setting Tertiary care academic children's
      hospital. Subjects and Methods A 15-year retrospective review identified 71
      patients with intracranial complications of acute sinusitis. Primary outcome was
      need for revision surgery. Secondary outcomes were readmission, length of
      hospitalization, and long-term complications. Results This study is the largest
      to date examining this disease process. Overall, 69 (97%) patients had surgery;
      33 (46%) required revision surgery. Half of the patients with frontal sinus
      opacification underwent frontal sinus surgery at presentation (endoscopic,
      trephination, or cranialization). There was no difference in revision surgery
      between patients who had frontal sinus surgery and those who did not. Patients
      with frontal sinus surgery did not have a higher rate of complications or chronic
      sinusitis ( P > .05). Subdural abscess was associated with multiple surgical
      procedures (odds ratio, 20.0; P < .01). Thirty-four patients (49%) required
      neurosurgery. These patients had a longer length of stay (odds ratio, 11.0; P <
      .01) and a higher readmission rate ( P = .02). During the mean 92-month follow
      up, 22 patients (33%) had long-term complications, and there was 1 death (1.4%).
      Conclusion Almost half of this cohort required multiple surgical procedures. In
      particular, patients with subdural abscess had significantly higher rates of
      revision surgery. Type of frontal sinus surgery was not correlated with need for
      revision surgery and was not associated with an increased rate of complications.

PMID- 29582701
TI  - Extending the Duluth Model to Workplace Bullying: A Modification and Adaptation
      of the Workplace Power-Control Wheel.
AB  - Workplace bullying (WB) is an increasingly prevalent topic in the nursing
      literature. Recently, a new concept has been introduced into WB research to
      explain the motivations of WB instigators using elements of the Power-Control
      Wheel (PCW). Initially, this wheel was designed to assist intimate partner
      violence (IPV) targets/victims identify patterns of abuse and intervene with male
      batterers/instigators. Research examining IPV and victims/survivors of WB
      demonstrate that targets often share common abusive experiences, including
      intimidation, coercion and threats, isolation, and economic and emotional abuse.
      This article demonstrates clear support for the Duluth Model and its application
      to WB target experiences. Applications of this model to identify WB and assist
      individuals to identify and describe experiences of abusive work environments are
      discussed.

PMID- 29582702
TI  - Secular changes in the association between advanced maternal age and the risk of
      low birth weight: A cross-cohort comparison in the UK.
AB  - Existing studies provide contradictory evidence concerning the association
      between child health and advanced maternal age. A potential explanation for the
      lack of consensus on this issue is changes over time in the costs and benefits of
      giving birth at an advanced age. This is the first study to investigate secular
      changes in the characteristics of older mothers and in the association between
      advanced maternal age and child health. We use data from four UK cohort studies,
      covering births from 1958 to 2001, and use low birth weight (LBW) as a marker for
      child health. We find that across successive birth cohorts, the negative
      association between advanced maternal age and LBW becomes progressively weaker;
      and that this pattern is partially explained by secular changes in the
      characteristics of older mothers. Our results suggest that associations between
      maternal age and child outcomes are tied to a specific population and point in
      time.

PMID- 29582703
TI  - Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes.
AB  - Objective To present 5-year outcomes from a prospective cohort of patients with
      obstructive sleep apnea (OSA) who were treated with upper airway stimulation
      (UAS) via a unilateral hypoglossal nerve implant. Study Design A multicenter
      prospective cohort study. Setting Industry-supported multicenter academic and
      clinical trial. Methods From a cohort of 126 patients, 97 completed protocol, and
      71 consented to a voluntary polysomnogram. Those having continuous positive
      airway pressure failure with moderate to severe OSA, body mass index <32 kg/m2,
      and no unfavorable collapse on drug-induced sleep endoscopy were enrolled in a
      phase 3 trial. Prospective outcomes included apnea-hypopnea index (AHI), oxygen
      desaturation index, and adverse events, as well as measures of sleepiness,
      quality of life, and snoring. Results Patients who did and did not complete the
      protocol differed in baseline AHI, oxygen desaturation index, and Functional
      Outcomes of Sleep Questionnaire scores but not in any other demographics or
      treatment response measures. Improvement in sleepiness (Epworth Sleepiness Scale)
      and quality of life was observed, with normalization of scores increasing from
      33% to 78% and 15% to 67%, respectively. AHI response rate (AHI <20 events per
      hour and >50% reduction) was 75% (n = 71). When a last observation carried
      forward analysis was applied, the responder rate was 63% at 5 years. Serious
      device-related events all related to lead/device adjustments were reported in 6%
      of patients. Conclusions Improvements in sleepiness, quality of life, and
      respiratory outcomes are observed with 5 years of UAS. Serious adverse events are
      uncommon. UAS is a nonanatomic surgical treatment with long-term benefit for
      individuals with moderate to severe OSA who have failed nasal continuous positive
      airway pressure.

PMID- 29582704
TI  - Maternal sensitivity in rural Andean and Amazonian Peru.
AB  - In the current study, we observed 12 mothers with a 4-21-month-old infant during
      their daily activities for around 3 h per dyad, focusing on daily caregiving
      practices such as feeding, bathing, and soothing in the rural multiple-caregiver
      cultural contexts of the Andean and Amazonian parts of Peru. Overall, sensitivity
      levels were high, with an average of 7.33 (out of 9), and 7 out of the 12 mothers
      scoring in the high range (scores 7-9), and the remaining 5 in the good-enough
      range (scores 5-6). In-depth descriptions of mother-infant interactions show that
      these high sensitivity levels reflect mothers' ability to multitask, combining
      household and agricultural chores with high sensitive responsiveness to their
      infants' signals. The presence of multiple caregivers seemed to allow mothers to
      make sure the infants were well attended when they were temporarily unavailable
      but combined with quick renewed availability if the infant seemed to need
      maternal proximity.

PMID- 29582706
TI  - Predictors of sensitive parenting in urban slums in Makassar, Indonesia.
AB  - In the context of urban slums in Makassar in Indonesia, this study aimed to test
      whether maternal sensitivity was predicted by maternal history of childhood
      maltreatment, and whether this association was mediated by current partner
      conflict and current cumulative sociodemographic risk. A total of 98 mothers and
      their 2-4-year-old children were videotaped in a naturalistic observation.
      Maternal sensitivity was coded using the Ainsworth scales. In addition, mothers
      were interviewed to assess childhood trauma, current partner conflict, and
      current sociodemographic risk. There was a significant negative correlation
      between maternal experienced childhood maltreatment and observed maternal
      sensitivity. Current partner conflict and sociodemographic risk did not mediate
      the association between childhood maltreatment and maternal sensitivity.

PMID- 29582705
TI  - Comparative assessment of prophylactic transfusions of platelet concentrates
      obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic
      hematopoietic stem cell transplantation.
AB  - OBJECTIVES: Whole blood-derived platelet concentrates can be obtained by the
      platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies
      have shown that BC-PCs display lower in vitro platelet activation, but scarce
      information exists regarding transfusion efficacy. We have performed a
      retrospective study assessing platelet transfusion in patients undergoing
      allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and
      after the implementation of BC-PCs. METHODS: We reviewed clinical records
      corresponding to 70 PRP-PCs and 86 BC-PCs prophylactic transfusions, which were
      performed to 55 AHCT patients. Transfusion efficacy was assessed by the 24-h post
      transfusion corrected count increment (24-h CCI) and bleeding events. Clinical
      factors affecting transfusion outcome were also investigated. RESULTS: Clinical
      characteristics and the total number of platelet transfusions were similar among
      groups. Mean donor exposure was 5.8 and 5.0 in each single PRP-PCs and BC-PCs
      transfusion, respectively (p < 0.01). The 24-h CCI was significantly higher in
      patients transfused with BC-PCs than in those receiving PRP-PCs (8.3[2.7-13.4]
      vs. 4.7[1.3-8.1]; p < 0.01). Independent predictors of poor platelet transfusion
      response included diagnosis other than acute leukemia (HR 8.30; 95% CI 1.96
      35.22; p = 0.004), splenomegaly (HR 8.75; 95% CI 2.77-27.60; p < 0.001), graft
      versus host disease prophylaxis different from cyclosporine A and methotrexate
      (HR 3.96; 95% CI 1.55-10.14; p = 0.004) and PRP-PCs transfusion (HR 4.54; 95% CI
      1.72-12.01; p = 0.002). There were no differences between both groups regarding
      the bleeding events. CONCLUSION: In the AHCT setting, we hypothesize that BC-PCs
      transfusion, when compared to PRP-PCs, results in higher CCI and reduced donor
      exposure, but provides no significant benefit regarding bleeding outcome.

PMID- 29582707
TI  - Decentralisation of Brazil's HIV/AIDS programme: intended and unintended
      consequences.
AB  - Brazil's response to the HIV/AIDS epidemic was characterised by an innovative
      alliance of governmental and non-governmental actors inspired by a strong
      progressive tradition in public health. Brazil eventually moved to decentralise
      HIV/AIDS programmes to its states and cities, a policy endorsed and supported
      financially by the World Bank as consistent with the mix of public and private
      elements central to the country's HIV/AIDS strategy. However, decentralisation
      has not provided the results anticipated. Through interviews with key informants,
      government officials and patient advocates as well as observation of treatment
      sites, we outline how the shift of administration and resources to state and
      municipal bodies operated in practice. The Bank promoted decentralisation as an
      uncontroversial technical matter, and its programmatic guidelines implied that
      the nonprofit sector would be strengthened by it. However, instead of bringing
      HIV/AIDS policy closer to the grassroots, decentralisation has undermined the
      country's early work and opened the door to a rejuvenated epidemic by empowering
      unsympathetic local elites, marginalising the human rights focus, and removing
      federal oversight. Its experience holds crucial lessons for developing countries
      facing similar conditions.

PMID- 29582708
TI  - Peritoneal and scrotal carcinomas of unknown origin in two bovine calves.
AB  - Two unrelated bovine beef calves, aged 2 mo and 3 mo, were presented to The Ohio
      State University Veterinary Medical Center because of scrotal swelling and
      abdominal distension. On postmortem examination, there was abundant peritoneal
      fluid and numerous small friable masses covering all peritoneal surfaces and
      extending into the scrotum via the tunica vaginalis, with no identifiable primary
      neoplasm. Based on light microscopy, differential diagnoses included malignant
      mesothelioma and anaplastic carcinoma. Immunohistochemically, the neoplasms
      labeled positive for cytokeratin, and negative for vimentin and calretinin.
      Neoplastic cells contained periodic acid-Schiff-positive, diastase-resistant
      cytoplasmic granules, and lacked Alcian blue-positive, hyaluronidase-negative
      cytoplasmic vacuoles. Ultrastructurally, the cells had features of carcinoma,
      including secretory granules, and lacked typical features of mesothelioma, such
      as long slender microvilli. Our final diagnosis was carcinoma in both calves,
      despite the equivocal gross and light microscopic findings. We propose that a
      presumptive diagnosis of peritoneal mesothelioma in bovine calves should be
      avoided without corroboration by a combination of histology, histochemistry,
      immunohistochemistry, and, if possible, electron microscopy.

PMID- 29582709
TI  - Adenoviral hemorrhagic disease in California mule deer, 1990-2014.
AB  - We reviewed case records from the California Animal Health and Food Safety
      (CAHFS) laboratory and the California Department of Fish and Wildlife (CDFW)
      spanning 25 years (1990-2014) for all deer accessions submitted to CAHFS for
      pathology and/or histopathology, with and without a diagnosis of adenoviral
      hemorrhagic disease (AHD), in order to determine the prevalence of AHD in
      California. We also examined spatial and temporal distribution, age, and mule
      deer subspecies in deer that died from AHD. Of 483 deer submitted to CAHFS for
      diagnostic testing in 1990-2014, 17.2% were diagnosed with confirmed AHD, and
      26.5% were confirmed plus suspected cases of AHD. Columbian black-tailed deer (
      Odocoileus hemionus columbianus), particularly fawns and juveniles, were most
      frequently affected. Deer adenovirus ( Odocoileus adenovirus 1; OdAdV-1) was
      detected by immunohistochemistry in archived CDFW formalin-fixed, paraffin
      embedded tissues from deer that died in mortality events in 1981, 1983, and 1986
      1987. OdAdV-1 is a common cause of hemorrhagic disease mortality events in
      California deer, and mortality as a result of AHD is documented as early as 1981.

PMID- 29582710
TI  - Dosing characteristics of oral treprostinil in real-world clinical practice.
AB  - Pharmacokinetic studies with oral treprostinil demonstrate that three times daily
      (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with
      twice daily (BID) dosing. TID dosing may allow for faster titration, higher total
      daily doses, and potentially improve the tolerability of oral trepostinil. This
      analysis, which looks at the real-world dosing of oral treprostinil, supports the
      utility of TID dosing.

PMID- 29582711
TI  - The role of path length- and speed-related factors for the enhancement of section
      performance in alpine giant slalom.
AB  - Knowing how to enhance alpine skiing performance is essential for effective
      coaching. The purpose of this study was to explore the role of path length- and
      speed-related factors for performance enhancement, while skiing on a
      homogeneously set/constantly inclined giant slalom course section (average gate
      distance: 27 m; offset: 8 m; slope inclination: 26 degrees ). During a video
      based three-dimensional kinematic field-experiment, the data of six athletes who
      skied a two-gate section on four different types of skis were collected. The
      performance parameter analysed was section time. The performance predictors
      analysed were centre of mass (CoM), path length and the change in specific
      mechanical energy per entrance speed along the analysed section. Furthermore,
      since the current study examined alpine skiing performance within short sections,
      the skier's entrance speed was also considered. Classified as a high-performance
      and a low-performance group based on section time, slow and fast trials
      significantly differed in CoM path length, the change in specific mechanical
      energy per entrance speed and entrance speed. The entrance speed of all trials
      analysed ranged between 15.25 and 17.66 m/s. In trials with both high and low
      entrance speed, the change in specific mechanical energy per entrance speed was
      found to be more relevant for the prediction of section time than CoM path
      length. However, further studies should investigate whether such a prioritization
      can be unrestrictedly generalized to other situations, such as entrance speeds,
      course sets, slope inclinations and competition disciplines different to those
      assessed in the current study.

PMID- 29582712
TI  - Why do stroke survivors not receive recommended amounts of active therapy?
      Findings from the ReAcT study, a mixed-methods case-study evaluation in eight
      stroke units.
AB  - OBJECTIVE: To identify why the National Clinical Guideline recommendation of 45
      minutes of each appropriate therapy daily is not met in many English stroke
      units. DESIGN: Mixed-methods case-study evaluation, including modified process
      mapping, non-participant observations of service organisation and therapy
      delivery, documentary analysis and semi-structured interviews. SETTING: Eight
      stroke units in four English regions. SUBJECTS: Seventy-seven patients with
      stroke, 53 carers and 197 stroke unit staff were observed; 49 patients, 50 carers
      and 131 staff participants were interviewed. RESULTS: Over 1000 hours of non
      participant observations and 433 patient-specific therapy observations were
      undertaken. The most significant factor influencing amount and frequency of
      therapy provided was the time therapists routinely spent, individually and
      collectively, in information exchange. Patient factors, including fatigue and
      tolerance influenced therapists' decisions about frequency and intensity,
      typically resulting in adaptation of therapy rather than no provision. Limited
      use of individual patient therapy timetables was evident. Therapist staffing
      levels were associated with differences in therapy provision but were not the
      main determinant of intensity and frequency. Few therapists demonstrated
      understanding of the evidence underpinning recommendations for increased therapy
      frequency and intensity. Units delivering more therapy had undertaken patient
      focused reorganisation of therapists' working practices, enabling them to provide
      therapy consistent with guideline recommendations. CONCLUSION: Time spent in
      information exchange impacted on therapy provision in stroke units.
      Reorganisation of therapists' work improved alignment with guidelines.

PMID- 29582713
TI  - A mixed treatment comparison on efficacy and safety of treatments for spasticity
      caused by multiple sclerosis: a systematic review and network meta-analysis.
AB  - OBJECTIVES: This study is aimed at providing a quantitative evaluation on
      different therapies of spasticity caused by multiple sclerosis. DATA SOURCES:
      PubMed and Embase database. REVIEW METHODS: We searched for randomized controlled
      trials that met the requirements. Percentages of improved patients' spasticity
      scale, mild adverse effect and severe adverse effect were extracted as outcomes.
      The forest plots accompanied with surface under the cumulative ranking curves
      were used to reveal the efficacy and safety of these therapies. RESULTS: In all,
      23 randomized controlled trials with a total of 2720 patients were included in
      our study. Cannabinoids and botulinum toxin had shown a significantly better
      efficacy than placebo in the percentage of improved patients. Botulinum toxin
      also showed such significant difference compared with tizanidine and baclofen. No
      significant difference was found in spasticity scale. Cannabinoids, tizanidine
      and diazepam had significantly more mild adverse effect reports than placebo.
      Surface under the cumulative ranking curves suggested that cannabinoids,
      botulinum toxin and transcutaneous electric nerve stimulation were preferable
      therapies. CONCLUSIONS: We recommended botulinum toxin as the optimal
      intervention for multiple sclerosis-related spasticity. Cannabinoids and
      transcutaneous electric nerve stimulation could also be considered as multiple
      sclerosis-related spasticity treatments but their safety remained to be verified.

PMID- 29582714
TI  - The impact of Nordic walking training on the gait of the elderly.
AB  - The purpose of the current study was to define the impact of regular practice of
      Nordic walking on the gait of the elderly. Thereby, we aimed to determine whether
      the gait characteristics of active elderly persons practicing Nordic walking are
      more similar to healthy adults than that of the sedentary elderly. Comparison was
      made based on parameters computed from three inertial sensors during walking at a
      freely chosen velocity. Results showed differences in gait pattern in terms of
      the amplitude computed from acceleration and angular velocity at the lumbar
      region (root mean square), the distribution (Skewness) quantified from the
      vertical and Euclidean norm of the lumbar acceleration, the complexity (Sample
      Entropy) of the mediolateral component of lumbar angular velocity and the
      Euclidean norm of the shank acceleration and angular velocity, the regularity of
      the lower limbs, the spatiotemporal parameters and the variability (standard
      deviation) of stance and stride durations. These findings reveal that the pattern
      of active elderly differs significantly from sedentary elderly of the same age
      while similarity was observed between the active elderly and healthy adults.
      These results advance that regular physical activity such as Nordic walking may
      counteract the deterioration of gait quality that occurs with aging.

PMID- 29582716
TI  - Amygdala - and serum - neurotrophic factor levels depend on rearing condition in
      male rats.
AB  - Early life experiences could determine brain and behavioral development.
      Neurotrophic factors are likely to mediate the effects of the experience on brain
      structures and function. Brain-derived neurotrophic factor (BDNF) plays a central
      role in psychiatric disorders. To investigate the effects of early rearing
      condition on the amygdala - and serum - BDNF levels, we reared male Wistar rats
      from weaning (postnatal days 21) to adulthood (postnatal days 119) in three
      different rearing conditions: (1) enriched, (2) standard and (3) isolated. We
      found that long-term post-weaning environmental enrichment leads to lower
      amygdala - and serum - BDNF levels as well as lower brain weights. Grouped
      rearing in standard laboratory cages enhanced body weight. Thus, early rearing
      condition might play a crucial role in adult healthiness by predetermining
      individual BDNF profiles.

PMID- 29582717
TI  - Maternal protein malnutrition: effects on prostate development and adult disease.
AB  - Well-controlled intrauterine development is an essential condition for many
      aspects of normal adult physiology and health. This process is disrupted by poor
      maternal nutrition status during pregnancy. Indeed, physiological adaptations
      occur in the fetus to ensure nutrient supply to the most vital organs at the
      expense of the others, leading to irreversible consequences in tissue formation
      and differentiation. Evidence indicates that maternal undernutrition in early
      life promotes changes in key hormones, such as glucocorticoids, growth hormones,
      insulin-like growth factors, estrogens and androgens, during fetal development.
      These alterations can directly or indirectly affect hormone release, hormone
      receptor expression/distribution, cellular function or tissue organization, and
      impair tissue growth, differentiation and maturation to exert profound long-term
      effects on the offspring. Within the male reproductive system, maternal protein
      malnutrition alters development, structure, and function of the gonads, testes
      and prostate gland. Consequently, these changes impair the reproductive capacity
      of the male offspring. Further, permanent alterations in the prostate gland occur
      at the molecular and cellular level and thereby affect the onset of late life
      diseases such as prostatitis, hyperplasia and even prostate cancer. This review
      assembles current thoughts on the concepts and mechanisms behind the
      developmental origins of health and disease as they relate to protein
      malnutrition, and highlights the effects of maternal protein malnutrition on rat
      prostate development and homeostasis. Such insights on developmental trajectories
      of adult-onset prostate disease may help provide a foundation for future studies
      in this field.

PMID- 29582715
TI  - Intercellular mitochondria trafficking highlighting the dual role of mesenchymal
      stem cells as both sensors and rescuers of tissue injury.
AB  - Mitochondria are crucial organelles that not only regulate the energy metabolism,
      but also the survival and fate of eukaryotic cells. Mitochondria were recently
      discovered to be able to translocate from one cell to the other. This phenomenon
      was observed in vitro and in vivo, both in physiological and pathophysiological
      conditions including tissue injury and cancer. Mitochondria trafficking was found
      to exert prominent biological functions. In particular, several studies pointed
      out that this process governs some of the therapeutic effects of mesenchymal stem
      cells (MSCs). In this review, we give an overview of the current knowledge on MSC
      dependent intercellular mitochondria trafficking and further discuss the recent
      findings on the intercellular mitochondria transfer between differentiated and
      mesenchymal stem cells, their biological significance and the mechanisms
      underlying this process.

PMID- 29582718
TI  - Use of a Single Xpert MTB/RIF Assay to Determine the Duration of Airborne
      Isolation in Hospitalized Patients With Suspected Pulmonary Tuberculosis.
AB  - BACKGROUNDHospitalized patients with suspected tuberculosis (TB) are placed in
      airborne isolation until 3 sputum smear samples are negative for acid-fast
      bacilli (AFB). The Xpert MTB/RIF assay ("Xpert") nucleic acid amplification test
      (NAAT) to identify Mycobacterium tuberculosis DNA and resistance to rifampicin is
      superior to AFB sputum smear microscopy for the diagnosis of TB.OBJECTIVETo
      compare the performance of a single Xpert to AFB smear microscopy for time to
      airborne infection isolation (AII) discontinuation.METHODSConsecutive patients
      over 17 years of age in AII for suspected pulmonary TB between October 1, 2014,
      and March 31, 2016, with leftover respiratory AFB samples were enrolled in this
      study. A single Xpert was performed on the first available sample. Demographic,
      clinical, and microbiological data were recorded for each patient. We compared
      the duration of AII using a single Xpert to AFB smear microscopy under multiple
      theoretical scenarios using Kaplan-Meier cumulative incidence curves and the log
      rank test.RESULTSIn total, 131 samples were included in our performance analysis
      of the Xpert, and 114 samples were included in our AII analysis. Overall, 81
      patients (65%) were immunosuppressed, of whom 46 (37%) were positive for human
      immunodeficiency virus (HIV). The sensitivity and specificity of Xpert for
      diagnosis of M. tuberculosis infection were 67% and 100%, respectively. Xpert was
      negative in all cases of nontuberculous mycobacteria. Use of a single Xpert
      reduced AII duration from a median of 67 hours per patient to 42 hours with usual
      reporting, to 26 hours with direct communication, and to 12 hours with immediate
      testing.CONCLUSIONSA single negative Xpert result can reduce AII duration
      compared to the AFB smear microscopy technique under multiple theoretical
      scenarios.Infect Control Hosp Epidemiol 2018;39:590-595.

PMID- 29582719
TI  - Urine Culture on Admission Impacts Antibiotic Use and Length of Stay: A
      Retrospective Cohort Study.
AB  - OBJECTIVETo examine the impact of urine culture testing on day 1 of admission on
      inpatient antibiotic use and hospital length of stay (LOS).DESIGNWe performed a
      retrospective cohort study using a national dataset from 2009 to 2014.SETTINGThe
      study used data from 230 hospitals in the United States.PARTICIPANTSAdmissions
      for adults 18 years and older were included in this study. Hospitalizations were
      matched with coarsened exact matching by facility, patient age, gender, Medicare
      severity-diagnosis related group (MS-DRG), and 3 measures of disease
      severity.METHODSA multilevel Poisson model and a multilevel linear regression
      model were used to determine the impact of an admission urine culture on
      inpatient antibiotic use and LOS.RESULTSMatching produced a cohort of 88,481
      patients (n=41,070 with a culture on day 1, n=47,411 without a culture). A urine
      culture on admission led to an increase in days of inpatient antibiotic use
      (incidence rate ratio, 1.26; P<.001) and resulted in an additional 36,607 days of
      inpatient antibiotic treatment. Urine culture on admission resulted in a 2.1%
      increase in LOS (P=.004). The predicted difference in bed days of care between
      admissions with and without a urine culture resulted in 6,071 additional bed days
      of care. The impact of urine culture testing varied by admitting
      diagnosis.CONCLUSIONSPatients with a urine culture sent on day 1 of hospital
      admission receive more days of antibiotics and have a longer hospital stay than
      patients who do not have a urine culture. Targeted interventions may reduce the
      potential harms associated with low-yield urine cultures on day 1.Infect Control
      Hosp Epidemiol 2018;39:547-554.

PMID- 29582720
TI  - Multidrug Resistant Acinetobacter baumanii: A 15-Year Trend Analysis.
AB  - From 2000 to 2009, rates of multidrug-resistant Acinetobacter baumanii increased
      10-fold to 0.2 per 1,000 patient days. From 2010 to 2015, however, rates markedly
      declined and have stayed below 0.05 per 1,000 patient days. Herein, we present a
      15-year trend analysis and discuss interventions that may have led to the
      decline.Infect Control Hosp Epidemiol 2018;39:608-611.

PMID- 29582721
TI  - Extensive hepatitis A outbreak in an urban childcare facility in Ireland,
      associated with considerable adult morbidity.
AB  - Hepatitis A infection results in a spectrum of illness from asymptomatic disease
      to severe fulminant hepatitis. Since 2000, <50 cases have been reported annually
      in Ireland. We report on an outbreak of hepatitis A associated with a childcare
      facility(CCF) in 2015 in Ireland. Between January and July 2015, 12 outbreak
      associated symptomatic hepatitis A cases were identified, including one delayed,
      retrospective diagnosis. Seven (58%) cases were adults, eight (67%) were male,
      six of the adults required hospitalisation. All 12 cases were confirmed on
      serology and the four cases that were genotyped were identical on phylogenetic
      analysis. Potential environmental exposures and hygiene practices at the CCF were
      investigated. Outbreak control measures included the provision of: hepatitis A
      information, infection prevention advice, hepatitis A vaccination to 554 CCF
      contacts, and voluntary closure of the CCF for deep-cleaning and staff education.
      From a healthcare perspective1, outbreak control costs were in excess of ?45 000.
      This outbreak illustrates the considerable adult morbidity that can occur in
      hepatitis A outbreaks, highlights the challenges in controlling a large CCF
      associated outbreak and the importance of early recognition by clinicians of
      hepatitis A.

PMID- 29582722
TI  - Intensity-Specific Differential Leukocyte DNA Methylation in Physical
      (In)Activity: An Exploratory Approach.
AB  - The aim of this exploratory study was to investigate how sedentary behavior (SB)
      and physical activity (PA) influence DNA methylation at a global, gene-specific,
      and health-related pathway level. SB, light PA (LPA), and moderate-to-vigorous PA
      (MVPA) were assessed objectively for 41 Flemish men using the SenseWear Pro 3
      Armband. CpG site-specific methylation in leukocytes was determined using the
      Illumina HumanMethylation 450 BeadChip. Correlations were calculated between time
      spent on the three PA intensity levels and global DNA methylation, using a z
      score-based method to determine global DNA methylation levels. To determine
      whether CpG site-specific methylation can be predicted by these three PA
      intensity levels, linear regression analyses were performed. Based on the
      significantly associated CpG sites at alpha = 0.005, lists were created including
      all genes with a promoter region overlapping these CpG sites. A biological
      pathway analysis determined to what extent these genes are overrepresented within
      several pathways. No significant associations were observed between global DNA
      methylation and SB (r = 0.084), LPA (r = -0.168), or MVPA (r = -0.125), although
      the direction of the correlation coefficients is opposite to what is generally
      reported in literature. SB has a different impact on global and gene-specific
      methylation than PA, but also LPA and MVPA affect separate genes and pathways.
      Furthermore, the function of a pathway seems to determine its association with
      SB, LPA, or MVPA. Multiple PA intensity levels, including SB, should be taken
      into account in future studies investigating the effect of physical (in)activity
      on human health through epigenetic mechanisms.

PMID- 29582723
TI  - Are Migraine and Tension-Type Headache Genetically Related? An Investigation of
      Twin Family Data.
AB  - Migraine and tension-type headache (TTH) are often viewed as distinct entities
      and defined as such in the International Classification of Headache Disorders,
      2nd edition (ICHD-II) criteria, although there is also empirical evidence to
      suggest they may be etiologically similar. This study aims to investigate whether
      migraine and TTH are etiologically related conditions. First, we explored whether
      migraine and TTH were associated with the same environmental and lifestyle risk
      factors at the population level. Second, we examined comorbidity of migraine and
      TTH in a twin design. By comparing the associations in monozygotic (MZ) and
      dizygotic (DZ) twin pairs, we investigated whether the comorbidity can be
      explained by genetic factors that influence both conditions. Results indicated
      that migraine and TTH were largely associated with the same environmental and
      lifestyle factors, including younger age, female sex, higher body mass index,
      more depression, stress at home, and less participation in regular exercise, with
      consistently stronger effects for migraine than for TTH. Migraine in one twin was
      significantly associated with TTH in the other twin. A stronger cross-trait,
      cross-twin association in MZ than DZ twins suggested that this comorbidity may
      also be partly due to shared genetic factors, although the difference in
      associations was not significant. In conclusion, our findings are consistent with
      the hypothesis that migraine and TTH have partly shared etiologies. For both
      treatment and research, it may be advisable not to make a rigid distinction, but
      to treat migraine and TTH as related conditions.

PMID- 29582724
TI  - Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive
      and Accurate Assessment of the Zygosity of Adult Twins.
AB  - Twin researchers face the challenge of accurately determining the zygosity of
      twins for research. As part of the annual questionnaire between 1999 and 2006,
      8,307 twins from the TwinsUK registry were asked to complete five questions
      (independently from their co-twin) to ascertain their self-perceived zygosity
      during childhood on up to five separate occasions. This questionnaire is known as
      the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its
      validation. Answers were scored and classified as monozygotic (MZ), dizygotic
      (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping
      data who had not been selected for zygosity. Of these, 3,859 individuals (46.5%
      of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and
      genotyping. Of the 708 individual twins whose answers meant that they were
      consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype
      data. Of the 945 individual twins consistently classed as DZ within
      questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored
      MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping,
      99.7% were DZ on genotyping if both twins consistently scored DZ. However, for
      the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and
      98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a
      single occasion provided a definitive classification of whether the twin was MZ
      or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a
      consistent classification of zygosity across multiple questionnaires. This study
      has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity
      in the absence of genotyping information.

PMID- 29582727
TI  - Maternal low-quality protein diet exerts sex-specific effects on plasma amino
      acid profile and alters hepatic expression of methyltransferases in adult rat
      offspring.
AB  - Nutrition during pregnancy and lactation is a critical factor in the development
      of the offspring. Both protein content and source in maternal diet affect
      neonatal health, but the long-term effects of maternal low-quality protein diet
      on the offspring are less clear. This study aimed to examine the effects of
      maternal low-quality protein diet on offspring's growth, development, circulating
      metabolites and hepatic expression of methyltransferases. Virgin Wistar rats were
      mated at 11 weeks of age. Dams were then maintained on either a chow diet with
      20% casein as the control group (C), or a low-quality protein diet with 20% wheat
      gluten as the experimental group (WG) throughout gestation and lactation. After
      weaning, all offspring were fed a control chow diet until the age of 20 weeks.
      Male WG offspring had significantly lower body weight and energy intake, whereas
      female WG offspring had significantly higher body weight and energy intake when
      compared with controls. Early life exposure to WG diet had no significant effect
      on circulating metabolites. However, fasting insulin concentrations and
      homoeostasis model assessment-insulin resistance were decreased in WG male and
      female offspring. Maternal low-quality protein diet increased plasma aspartic
      acid, glutamic acid, histidine, cystathione and decreased lysine in male WG
      offspring. Conversely, the same amino acids were reduced in female WG offspring.
      Adult offspring exposed to WG diet had significantly upregulated hepatic DNMT3a
      and DNMT3b expressions. Our study showed that there were differential effects of
      maternal poor-quality protein diet upon adult offspring's metabolism.

PMID- 29582728
TI  - Polymorphisms in the K13 Gene in Plasmodium falciparum from Different Malaria
      Transmission Areas of Kenya.
AB  - The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA)
      threatens malaria control globally. Mutations in the Kelch 13 (K13)-propeller
      domain have been useful in identifying ART resistance in SEA. ART combination
      therapy (ACT) remains highly efficacious in the treatment of uncomplicated
      malaria in Sub-Saharan Africa (SSA). However, it is crucial that the efficacy of
      ACT is closely monitored. Toward this effort, this study profiled the prevalence
      of K13 nonsynonymous mutations in different malaria ecological zones of Kenya and
      in different time periods, before (pre) and after (post) the introduction of ACT
      as the first-line treatment of malaria. Nineteen nonsynonymous mutations were
      present in the pre-ACT samples (N = 64) compared with 22 in the post-ACT samples
      (N = 251). Eight of these mutations were present in both pre- and post-ACT
      parasites. Interestingly, seven of the shared single-nucleotide polymorphisms
      were at higher frequencies in the pre-ACT than the post-ACT parasites. The A578S
      mutation reported in SSA and the V568G mutation reported in SEA were found in
      both pre- and post-ACT parasites, with their frequencies declining post-ACT.
      D584Y and R539K mutations were found only in post-ACT parasites; changes in these
      codons have also been reported in SEA with different amino acids. The N585K
      mutation described for the first time in this study was present only in post-ACT
      parasites, and it was the most prevalent mutation at a frequency of 5.2%. This
      study showed the type, prevalence, and frequency of K13 mutations that varied
      based on the malaria ecological zones and also between the pre- and post-ACT time
      periods.

PMID- 29582729
TI  - Detection of Immunoglobulin G Antibodies to Taenia solium Cysticercosis Antigen
      Glutathione-S-Transferase-rT24H in Malian Children Using Multiplex Bead Assay.
AB  - Blood samples from 805 students attending 42 elementary schools in Mopti,
      Sikasso, and Koulikoro regions, and Bamako district in Mali participated in a
      school water, sanitation, and hygiene intervention. Immunoglobulin (Ig) G
      responses to several antigens/pathogens were assessed by a multiplex bead assay
      (MBA), and the recombinant Taenia solium T24H antigen was included. Of all
      students tested, 8.0% were positive to rT24H, but in some schools 25-30%. A
      cluster of 12 widespread school locations showed not only a relative risk of 3.23
      for T. solium exposure and significantly higher IgG responses (P < 0.001) but
      also significantly lower elevation (P = 0.04) (m, above sea level) compared with
      schools outside the cluster. All schools at elevations < 425 m showed
      significantly higher IgG responses (P = 0.017) than schools at elevations >= 425
      m. The MBA is an excellent serological platform that provides cost-effective
      opportunities to expand testing in serosurveys.

PMID- 29582730
TI  - Safe Water and Hygiene Integration with Human Immunodeficiency Virus and
      Antenatal Services: Leveraging Opportunities for Public Health Interventions and
      Improved Service Uptake.
AB  - Integrating public health interventions with antenatal clinic (ANC) visits may
      motivate women to attend ANC, thereby improving maternal and neonatal health,
      particularly for human immunodeficiency virus (HIV)-infected persons. In 2009, in
      an integrated ANC/Preventing Mother-to-Child Transmission program, we provided
      free hygiene kits (safe storage containers, WaterGuard water treatment solution,
      soap, and oral rehydration salts) to women at their first ANC visit and refills
      at subsequent visits. To increase fathers' participation, we required partners'
      presence for women to receive hygiene kits. We surveyed pregnant women at
      baseline and at 12-month follow-up to assess ANC service utilization, HIV
      counseling and testing (HCT), test drinking water for residual chlorine, and
      observe handwashing. We conducted in-depth interviews with pregnant women,
      partners, and health workers. We enrolled 106 participants; 97 (92%) were found
      at follow-up. During the program, 99% of pregnant women and their partners
      received HCT, and 99% mutually disclosed. Fifty-six percent of respondents had >=
      4 ANC visits and 90% delivered at health facilities. From baseline to follow-up,
      the percentage of women who knew how to use WaterGuard (23% versus 80%, P <
      0.0001), had residual chlorine in stored water (0% versus 73%, P < 0.0001), had
      confirmed WaterGuard use (0% versus 70%, P < 0.0003), and demonstrated proper
      handwashing technique (21% versus 64% P < 0.0001) increased. Program participants
      showed significant improvements in water treatment and hygiene, and high use of
      ANC services and HCT. This evaluation suggests that integration of hygiene kits,
      refills, and HIV testing during ANC is feasible and may help improve household
      hygiene and increase use of health services.

PMID- 29582732
TI  - Molecular Markers of Plasmodium falciparum Drug Resistance in Parasitemic
      Pregnant Women in the Middle Forest Belt of Ghana.
AB  - Data on prevalence of antimalarial molecular resistance markers in pregnant women
      in Ghana is scarce. Prevalence of single nucleotide polymorphisms/haplotypes in
      the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes was assessed in a cross-sectional
      study involving 200 pregnant women. Almost 90% of infections were wild type at
      the Pfcrt gene whereas the Pfmdr1 NFD mutant haplotype occurred in 43% of
      samples. Prevalence of Pfdhfr/Pfdhps quadruple mutation was 92.6% whereas
      Pfdfr/Pfdhps quintuple mutation with K540E was not observed. The study provides
      important updates of antimalarial resistance markers in Ghanaian pregnant women
      and suggests increased tolerance to one of the first-line treatment options in
      Ghana: artemether-lumefantrine. The data support the view that sulfadoxine
      pyrimethamine is still efficacious for intermittent preventive treatment in
      Ghana, but the impact of increased doses on selection of mutations needs to be
      assessed. Continuing the surveillance of resistance markers is important to
      inform changes in antimalarial drug policy in pregnancy.

PMID- 29582731
TI  - Vector-Borne Disease is a Common Cause of Hospitalized Febrile Illness in India.
AB  - Acute febrile illness (AFI) is a major cause of morbidity and mortality in India
      and other resource-limited settings, yet systematic etiologic characterization of
      AFI has been limited. We prospectively enrolled adults (N = 970) and children
      (age 6 months to 12 years, N = 755) admitted with fever from the community to
      Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We
      systematically obtained a standardized clinical history, basic laboratory
      testing, and microbiologic diagnostics on enrolled participants. Results from
      additional testing ordered by treating clinicians were also recorded. A
      microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met
      standardized case definitions for pneumonia and meningitis without an identified
      organism; 559 (32%) were assigned a clinical diagnosis in the absence of a
      confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were
      the most common cause of AFI in adults including dengue (N = 188, 19%), malaria
      (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections
      (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In
      children, pneumonia was the most common cause of AFI (N = 214, 28%) and death.
      Bacteremia was found in 68 (4%) participants. Central nervous system infections
      occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is
      diverse, highly seasonal, and difficult to differentiate on clinical grounds
      alone. Diagnostic strategies adapted for season and age may reduce diagnostic
      uncertainty and identify causative organisms in treatable, fatal causes of AFI.

PMID- 29582733
TI  - The Elderly Respond to Antimony Therapy for Cutaneous Leishmaniasis Similarly to
      Young Patients but Have Severe Adverse Reactions.
AB  - There is evidence that elderly patients with cutaneous leishmaniasis (CL) have
      more mucosal and disseminated diseases than young patients and their cells
      produce less antigen-induced interferon (IFN)-gamma. Herein, we compared the
      roles of interleukin (IL)-10 and IL-15 as modulators of antigen-induced immune
      responses and the incidence of adverse reaction and response to therapy in young
      versus elderly patients with CL. Study participants included 35 senior (60-85
      years) and 35 young (18-40 years) patients who had a diagnosis of CL documented
      by typical cutaneous lesions containing Leishmania braziliensis DNA. Elderly
      patients had less lymph node enlargement. Antigen-induced blood cell cytokine
      responses were studied in the absence or presence of IL-10 antibody or
      exogenously added recombinant IL-15. The ratio of IFN-gamma/IL-10 was lower in
      elderly patients, and IFN-gamma production was enhanced by either neutralization
      of IL-10 or exogenous recombinant IL-15 in blood cells from elderly but not young
      patients. Patients were treated three times weekly with antimony at 20 mg/kg/day
      for 20 doses. Although there was no difference in response to therapy between the
      two groups, two young patients needed rescue therapy with amphotericin B.
      Ventricular arrhythmias and ventricular overload were more frequent in elderly
      patients. We conclude that elderly patients have alterations in the immune
      response that may influence clinical manifestations, but we did not find that
      they had a higher failure rate than young subjects to antimony therapy. However,
      because of the high rate of electrocardiographic abnormalities during therapy,
      antimony should not be used in elderly patients with CL.

PMID- 29582734
TI  - Knowledge of Norovirus and Attitudes toward a Potential Norovirus Vaccine in
      Rural Guatemala: A Cross-Sectional Exploratory Survey.
AB  - Given limited data on norovirus vaccine acceptance, we performed an exploratory
      survey in a rural Guatemalan community on knowledge, interest, and willingness to
      pay (WTP) for a norovirus vaccine. Cluster-randomized households with children
      aged 6 weeks to 17 years were enrolled into one of two norovirus surveillance
      studies: 1) a prospective cohort (N = 207 households) and 2) two separate,
      community-based, cross-sectional surveys (N = 420 households). After completion
      of the surveillance study, vaccine surveys were completed by 564 (90%) of 627
      households. Most households correctly answered questions regarding norovirus
      symptoms and transmission; 97% indicated interest in a hypothetical norovirus
      vaccine. Households with higher education had greater WTP for a vaccine
      (prevalence ratios = 2.2, 95% confidence interval: 1.2-3.1) and households with
      lower WTP were more likely to use pharmacies, the Ministry of Health, and radios
      for health care and information. These results suggest that a future norovirus
      vaccination program could be acceptable and feasible even in rural areas.

PMID- 29582735
TI  - A Revival of Epidemiological Entomology in Senegal.

PMID- 29582736
TI  - Seroprevalence of Hepatitis A Virus, Hepatitis E Virus, and Helicobacter pylori
      in Rural Communities of the Bolivian Chaco, 2013.
AB  - In the Bolivian Chaco, south-east of Bolivia, studies conducted over the past
      three decades reported hepatitis A virus (HAV) and Helicobacter pylori
      seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV)
      prevalence was previously found to be 6-7% but is probably an underestimate
      because of the poor sensitivity of the assays used. In November 2013, we
      conducted a cross-sectional study of 263 healthy volunteers from two rural
      communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori
      seroprevalence 10-20 years following the previous surveys. Hepatitis A virus
      seroprevalence was 95%, with universal exposure after the first decade of life;
      HEV seroprevalence was considerably higher (31-35%) than that previously
      reported; H. pylori seroprevalence was 59%, with an age-dependent distribution.
      The high prevalence of these infections suggests that major efforts are still
      needed to reduce fecal-oral transmission and to improve human health in the
      Bolivian Chaco.

PMID- 29582737
TI  - Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient
      Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean
      Area.
AB  - This case report highlights the risk of severe cutaneous leishmaniasis (CL) by
      Leishmania infantum in patients undergoing immunosuppressant therapy who either
      live in an endemic area or are visiting in the transmission season. The case
      patient, resident in Majorca (Balearic Islands), presented 12 disseminated
      erythematous skin lesions, 1-6 cm in diameter, located on the scalp, cheek,
      umbilical region, and lower extremities 8 years after undergoing anti-tumor
      necrosis factor (TNF) therapy. Parasite presence in peripheral blood and high
      levels of specific antibodies were also observed, indicating a possible risk of
      CL shifting toward a visceral infection. However, once CL was diagnosed, anti-TNF
      therapy was discontinued and liposomal amphotericin B was administered, resulting
      in a complete healing of lesions, no Leishmania DNA detection in blood, and an
      important serological decrease in antibodies. The lack of data on the supposed
      epidemiological association between leishmaniasis and immunosuppressive therapy
      highlights the importance of implementing surveillance systems in endemic areas.
      No obvious relationship was found based on the data provided by the Balearic
      Islands Epidemiological System, in contrast with data reported in nearby endemic
      areas. This indicates that if the suspected association is to be clarified,
      greater efforts are needed to report information about concomitant diseases and
      therapies in leishmaniasis patients.

PMID- 29582738
TI  - Article importance: Processes to evaluate the success of published articles are
      subjective.

PMID- 29582739
TI  - [Degre d'importance des articles : Les processus d'evaluation des articles
      publies sont subjectifs].

PMID- 29582740
TI  - Physician extenders on surgical services: the need for a systems perspective.
AB  - SUMMARY: Adding physician extenders (PEs) to surgical teams has the potential to
      affect care delivery in multiple ways. To develop evidence-based recommendations
      on integrating PEs into surgical teams, we must recognize that patient care is a
      complex, adaptive system and requires a health systems perspective to understand
      how changes will affect outcomes. It is the best method of assessing the system
      adaptations and trade-offs of adding PEs prior to implementation. Such work would
      help to optimize research and management of limited health care resources.

PMID- 29582741
TI  - Idle hands? What we know about surgeon unemployment in Canada.
AB  - SUMMARY: The topic of unemployment and underemployment of Canadian general
      surgeons is being discussed more frequently despite relatively little evidence on
      the magnitude or impact of the problem. Using existing and new sources of health
      human resource data, a more accurate understanding of the situation can be
      attained. Although outright surgeon unemployment is rare, there is a population
      of dissatisfied new graduates who feel cornered into underemployment or locums.
      The number of practising general surgeons has outpaced population growth in
      recent years. However, the number of new trainees peaked in 2010 and has been
      decreasing steadily since then. There are many pressures that stand in the way of
      more accurate management of the general surgery workforce. A better understanding
      of the subject and better leadership at the national level may help improve
      system performance.

PMID- 29582742
TI  - The Canadian Army Medical Corps affair of 1916 and Surgeon General Guy Carleton
      Jones.
AB  - SUMMARY: The rapid expansion of military medical service in the First World War,
      successfully completed under the direction of Surgeon General Guy Carleton Jones,
      remains an extraordinary achievement in Canada's history. In 1916, a conflict of
      personalities threatened confidence in the service. Eventually Prime Minister Sir
      Robert Borden's intervention restored the status quo, but the affair eclipsed
      Jones's outstanding career.

PMID- 29582743
TI  - Associations between provider and hospital volumes and postoperative mortality
      following total hip arthroplasty in New Brunswick: results from a provincial
      level cohort study.
AB  - BACKGROUND: Several international studies have reported negative associations
      between hospital and/or provider volume and risk of postoperative death following
      total hip arthroplasty (THA). The only Canadian studies to report on this have
      been based in Ontario and have found no such association. We describe
      associations between postoperative deaths following THA and provider caseload
      volume, also adjusted for hospital volume, in a population-based cohort in New
      Brunswick. METHODS: Our analyses are based on hospital discharge abstract data
      linked to vital statistics and to patient registry data. We considered all first
      known admissions for THA in New Brunswick between Jan. 1, 2007, and Dec. 31,
      2013. Provider volume was defined as total THAs performed over the preceding 2
      years. We fit logistic regression models to identify odds of dying within 30 and
      90 days according to provider caseload volume adjusted for selected personal and
      contextual characteristics. RESULTS: About 7095 patients were admitted for THA in
      New Brunswick over the 7-year study period and 170 died within 30 days. We found
      no associations with provider volume and postoperative mortality in any of our
      models. Adjustment for contextual characteristics or hospital volume had no
      effects on this association. CONCLUSION: Our results suggest that patients
      admitted for hip replacements in New Brunswick can expect to have similar risk of
      death regardless of whether they are admitted to see a provider with high or low
      THA volumes and of whether they are admitted to the province's larger or smaller
      hospitals.

PMID- 29582744
TI  - Surgical intervention in pediatric trauma at a level 1 trauma hospital: a
      retrospective cohort study and report of cost data.
AB  - BACKGROUND: Given that the management of severely injured children requires
      coordinated care provided by multiple pediatric surgical subspecialties, we
      sought to describe the frequency and associated costs of surgical intervention
      among pediatric trauma patients admitted to a level 1 trauma centre in
      southwestern Ontario. METHODS: All pediatric (age < 18 yr) trauma patients
      treated at the Children's Hospital - London Health Sciences Centre (CH-LHSC)
      between 2002 and 2013 were included in this study. We compared patients
      undergoing surgical intervention with a nonsurgical group with respect to
      demographic characteristics and outcomes. Hospital-associated costs were
      calculated only for the surgical group. RESULTS: Of 784 injured children, 258
      (33%) required surgery, 40% of whom underwent orthopedic interventions. These
      patients were older and more severely injured, and they had longer lengths of
      stay than their nonsurgical counterparts. There was no difference in mortality
      between the groups. Seventy-four surgical patients required intervention within 4
      hours of admission; 45% of them required neurosurgical intervention. The median
      cost of hospitalization was $27 571 for the surgical group. CONCLUSION: One-third
      of pediatric trauma patients required surgical intervention, of whom one-third
      required intervention within 4 hours of arrival. Despite the associated costs,
      the surgical treatment of children was associated with comparable mortality to
      nonsurgical treatment of less severely injured patients. This study represents
      the most recent update to the per patient cost for surgically treated pediatric
      trauma patients in Ontario, Canada, and helps to highlight the multispecialty
      care needed for the management of injured children.

PMID- 29582745
TI  - Regional differences in aortic valve replacements: Atlantic Canadian experience.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is evolving rapidly
      and is increasingly being adopted in the treatment of aortic valve disease. The
      goal of this study was to examine regional differences in surgical aortic valve
      replacement (SAVR) and TAVI across Atlantic Canada. METHODS: We identified all
      patients who underwent SAVR or TAVI between Jan. 1, 2010, and Dec. 31, 2014, in
      New Brunswick, Nova Scotia and Newfoundland and Labrador. Data obtained included
      patient demographic characteristics and surgical procedure details. We performed
      univariate descriptive analyses and calculated crude and age- and sex-adjusted
      incidence rates. RESULTS: A total of 3042 patients underwent SAVR or TAVI during
      the study period, 1491 in Nova Scotia, 1042 in New Brunswick and 509 in
      Newfoundland and Labrador. Patient demographic characteristics were similar
      across regions. A much higher proportion of patients in Newfoundland and Labrador
      (43.6%) than in Nova Scotia (4.2%) or New Brunswick (13.6%) received a mechanical
      versus a bioprosthetic valve. Rates of TAVI increased over the study period, with
      New Brunswick adopting their program before Nova Scotia (144 v. 74 procedures).
      Adjusted rates of all AVR procedures remained stable in Nova Scotia (40-50 per
      100 000 people). Adjusted rates were lower in New Brunswick and Newfoundland and
      Labrador than in Nova Scotia; they increased slowly in New Brunswick over the
      study period. CONCLUSION: Despite geographical proximity and similar patient
      demographic characteristics, there existed regional differences in the management
      of aortic valve disease within Atlantic Canada. Further study is required to
      determine whether the observed differences in age- and sex-adjusted rates of AVR
      may be explained by geographical disease-related differences, varying practice
      patterns or barriers in access to care.

PMID- 29582746
TI  - Intraoperative cell salvage with autologous transfusion in elective right or
      repeat hepatectomy: a propensity-score-matched case-control analysis.
AB  - BACKGROUND: Liver resection may be associated with substantial blood loss, and
      cell saver use has been recommended for patients at high risk. We performed a
      study to compare the allogenic erythrocyte transfusion rate after liver resection
      between patients who had intraoperative cell salvage with a cell saver device
      versus patients who did not. Our hypothesis was that cell salvage with autologous
      transfusion would reduce the allogenic blood transfusion rate. METHODS: Cell
      salvage was used selectively in patients at high risk for intraoperative blood
      loss based on preoperatively known predictors: right and repeat hepatectomy.
      Patients who underwent elective right or repeat hepatectomy between Nov. 9, 2007,
      and Jan. 27, 2016 were considered for the study. Data were retrieved from a liver
      resection database and were analyzed retrospectively. Patients with cell saver
      use (since January 2013) constituted the experimental group, and those without
      cell salvage (2007-2012), the control group. To reduce selection bias, we matched
      propensity scores. The primary outcome was the allogenic blood transfusion rate
      within 90 days postoperatively. Secondary outcomes were the number of transfused
      erythrocyte units, and rates of overall and infectious complications. RESULTS:
      Ninety-six patients were included in the study, 41 in the cell saver group and 55
      in the control group. Of the 96, 64 (67%) could be matched, 32 in either group.
      The 2 groups were balanced for demographic and clinical variables. The allogenic
      blood transfusion rate was 28% (95% confidence interval [CI] 12.5%-43.7%) in the
      cell saver group versus 72% (95% CI 56.3%-87.5%) in the control group (p <
      0.001). The overall and infectious complication rates were not significantly
      different between the 2 groups. CONCLUSION: Intraoperative cell salvage with
      autologous transfusion in elective right or repeat hepatectomy reduced the
      allogenic blood transfusion rate.

PMID- 29582747
TI  - Training surgical residents to use a framework to promote shared decision-making
      for patients with poor prognosis experiencing surgical emergencies.
AB  - BACKGROUND: Patients with poor underlying prognosis experiencing surgical
      emergencies face challenging treatment decisions. The Best Case/Worst Case
      (BC/WC) framework has improved shared decision-making by surgeons, but it is
      unclear whether residents can be similarly trained. We evaluated senior general
      surgical residents' acceptance of the BC/WC tool and their attitudes, confidence
      and actions before and after training. METHODS: Two-hour training included a
      didactic session, live demonstration, small-group practice and debriefing. We
      developed questionnaires to evaluate residents' attitudes, confidence and actions
      at 3 time points: before the intervention, after the intervention and 6 months
      after the intervention. We used the Ottawa Decision Support Framework
      Acceptability questionnaire to evaluate acceptability and a structured
      observation form to evaluate performance. RESULTS: Eighteen (50%) of 36 invited
      residents participated. Most residents (83%) felt that a new communication tool
      would be useful. Almost all (94%) used BC/WC in practice. Residents found the
      tool acceptable and useful to enhance preference-sensitive communications. They
      felt that the training was valuable and that role play was its greatest strength
      but that these situations were challenging to simulate. Barriers to BC/WC use
      included time constraints and difficulty defining the best and worst cases
      precisely. Summative attitudes and confidence scores were not different before
      and after the intervention; however, actions scores were higher after the
      intervention (p = 0.04). Residents performed a median of 15 (interquartile range
      13-17) of the 19 elements on the formative performance evaluation. Commonly
      missed items were narrating outcomes of palliative approaches, prompting
      deliberation and providing treatment recommendations. CONCLUSION: Senior
      residents found the BC/WC tool to be acceptable and useful, and are amenable to
      training in this type of communication. After training, self-reported actions
      scores increased, and observed performance was accurate.

PMID- 29582748
TI  - Airway management changes associated with rising radiologic incidence of external
      laryngotracheal injury.
AB  - BACKGROUND: Traumatic laryngeal injuries are uncommon life-threatening injuries
      that require prompt, rational management of a potentially precarious airway. It
      is unclear whether the current incidence of laryngotracheal injury is due to
      enhanced injury detection or increased occurrence. The objective of this study
      was to evaluate the relations between diagnostic imaging with both initial airway
      management and surgical treatment in patients with external laryngotracheal
      injuries (ELTIs) in Alberta. METHODS: In this large-scale population-based
      analysis, we used regional health databases containing inpatient admissions,
      emergency department visits and trauma service activations employing
      International Classification of Diseases diagnostic codes to identify all ELTIs
      diagnosed from Apr. 1, 1995, to Dec. 31, 2011, in adults (age >= 16 yr). We
      evaluated health records and diagnostic imaging for injury features, airway
      management, operative interventions and hospital length of stay (LOS). RESULTS:
      Eighty-nine patients met the inclusion criteria. The incidence of ELTIs increased
      over time, paralleling a rise in detection during the period incorporating
      greater computed tomography (CT) use (p = 0.002). Endotracheal tube intubation
      was performed in 8/30 cases (27%) in the pre-CT era, compared to 38/59 cases
      (64%) in the post-CT era (p = 0.001); the use of surgical intervention remained
      consistent. The largest contributors to increased endotracheal tube placements
      were the emergency department and emergency medical services. No change in
      survival was detected, but mean LOS among patients admitted for minor, isolated
      ELTIs increased by 2.3 (95% confidence interval 0.14-4.8) days (p = 0.06), mostly
      for patients admitted under critical care for mechanical ventilation. CONCLUSION:
      Management of ELTIs shifted from predominantly conservative airway monitoring to
      endotracheal tube intubation over the study period in spite of no clinically
      significant change in injury severity or operative intervention frequency. The
      location of endotracheal tube placement suggests less comfort with ELTI among
      first-responder and emergency personnel.

PMID- 29582750
TI  - Kidney paired donation and the unique challenges of kidney shipment in Canada.
AB  - SUMMARY: Kidney paired donation (KPD) programs are an effort to bridge the
      disparity between kidney supply and demand. These programs combine several
      incompatible donor-recipient pairs in a national paired exchange database,
      thereby increasing the number of compatible matches. But KPD programs face unique
      challenges, particularly the large distances that often separate donors and
      recipients. Here we discuss key factors to consider when transitioning from a
      donor travelling model to a kidney shipment model in the Canadian context.

PMID- 29582749
TI  - Is radiofrequency ablation of varicose veins a valuable option? A systematic
      review of the literature with a cost analysis.
AB  - BACKGROUND: Since the 1990s, new techniques for the treatment of varicose veins
      have emerged, including radiofrequency ablation (RFA) and laser treatment. We
      performed a study to compare the safety, efficacy and outcomes of RFA compared to
      those of open surgery and laser ablation for the treatment of varicose veins. We
      also carried out a cost analysis of RFA compared to open surgery to assess
      whether RFA could help free up operating room time by being performed in an
      outpatient context. METHODS: We conducted a systematic literature review
      (publication date May 2010-September 2013 for articles in English, January 1991
      September 2013 for those in French). We used several checklists to measure the
      quality of the studies. We also collected data on costing. RESULTS: The
      literature search identified 924 publications, of which 38 were retained for
      analysis: 15 literature reviews, 1 good-practice guideline and 22 new primary
      studies. The overall level of evidence was low to moderate owing to the limited
      sample sizes, lack of information on patient characteristics and lack of
      standardization of the outcome measures. However, the results obtained are
      consistent from study to study. In the short and medium term, RFA is considered
      as effective as open surgery or laser treatment (moderate level of evidence) and
      presents fewer major and minor complications than open surgery (low level of
      evidence). Radiofrequency ablation can be performed on an outpatient basis. We
      calculated that RFA would be about $110-$220 more expensive per patient than open
      surgery. CONCLUSION: Radiofrequency ablation is a valuable alternative to open
      surgery and would free up operating room time in a context of low accessibility.

PMID- 29582751
TI  - Patient-perceived barriers to radiation therapy for breast cancer.
AB  - SUMMARY: Studies have shown that a number of women do not receive adjuvant
      radiation therapy following breast-conserving surgery; the reasons have not been
      well investigated. We reviewed the charts of 267 patients in our institution who
      did not receive radiation therapy following surgery in order to determine patient
      stated reasons for nonreceipt. We found that 43% of patients did not receive
      radiation because they received a completion mastectomy. Excluding these
      patients, reasons for nonreceipt of radiation therapy were sorted into 9
      categories. Most patients declined radiation therapy (against physician advice).
      We identified 3 major barriers to receipt of radiation therapy: improper patient
      selection, transportation or ambulatory issues and patient fear surrounding
      radiation toxicity. All of these reasons are surmountable barriers to radiation
      receipt.

PMID- 29582752
TI  - Reduction of pancreatic anastomotic leakage after pancreaticoduodenectomy.

PMID- 29582753
TI  - The kinetoplastid-infecting Bodo saltans virus (BsV), a window into the most
      abundant giant viruses in the sea.
AB  - Giant viruses are ecologically important players in aquatic ecosystems that have
      challenged concepts of what constitutes a virus. Herein, we present the giant
      Bodo saltans virus (BsV), the first characterized representative of the most
      abundant group of giant viruses in ocean metagenomes, and the first isolate of a
      klosneuvirus, a subgroup of the Mimiviridae proposed from metagenomic data. BsV
      infects an ecologically important microzooplankton, the kinetoplastid Bodo
      saltans. Its 1.39 Mb genome encodes 1227 predicted ORFs, including a complex
      replication machinery. Yet, much of its translational apparatus has been lost,
      including all tRNAs. Essential genes are invaded by homing endonuclease-encoding
      self-splicing introns that may defend against competing viruses. Putative anti
      host factors show extensive gene duplication via a genomic accordion indicating
      an ongoing evolutionary arms race and highlighting the rapid evolution and
      genomic plasticity that has led to genome gigantism and the enigma that is giant
      viruses.

PMID- 29582754
TI  - Endogenous opioids in the nucleus accumbens promote approach to high-fat food in
      the absence of caloric need.
AB  - When relatively sated, people (and rodents) are still easily tempted to consume
      calorie-dense foods, particularly those containing fat and sugar. Consumption of
      such foods while calorically replete likely contributes to obesity. The nucleus
      accumbens (NAc) opioid system has long been viewed as a critical substrate for
      this behavior, mainly via contributions to the neural control of consumption and
      palatability. Here, we test the hypothesis that endogenous NAc opioids also
      promote appetitive approach to calorie-dense food in states of relatively high
      satiety. We simultaneously recorded NAc neuronal firing and infused a u-opioid
      receptor antagonist into the NAc while rats performed a cued approach task in
      which appetitive and consummatory phases were well separated. The results reveal
      elements of a neural mechanism by which NAc opioids promote approach to high-fat
      food despite the lack of caloric need, demonstrating a potential means by which
      the brain is biased towards overconsumption of palatable food.

PMID- 29582756
TI  - Lassa fever and global health security.

PMID- 29582755
TI  - Occurrence of long-term depression in the cerebellar flocculus during adaptation
      of optokinetic response.
AB  - Long-term depression (LTD) at parallel fiber (PF) to Purkinje cell (PC) synapses
      has been considered as a main cellular mechanism for motor learning. However, the
      necessity of LTD for motor learning was challenged by demonstration of normal
      motor learning in the LTD-defective animals. Here, we addressed possible
      involvement of LTD in motor learning by examining whether LTD occurs during motor
      learning in the wild-type mice. As a model of motor learning, adaptation of
      optokinetic response (OKR) was used. OKR is a type of reflex eye movement to
      suppress blur of visual image during animal motion. OKR shows adaptive change
      during continuous optokinetic stimulation, which is regulated by the cerebellar
      flocculus. After OKR adaptation, amplitudes of quantal excitatory postsynaptic
      currents at PF-PC synapses were decreased, and induction of LTD was suppressed in
      the flocculus. These results suggest that LTD occurs at PF-PC synapses during OKR
      adaptation.

PMID- 29582757
TI  - Pigs, pathogens, and public health.

PMID- 29582758
TI  - Impact of enhanced viral haemorrhagic fever surveillance on outbreak detection
      and response in Uganda.

PMID- 29582759
TI  - Tuberculosis on Lesvos: barriers to treatment.

PMID- 29582760
TI  - EUSeqMyTB to set standards and build capacity for whole genome sequencing for
      tuberculosis in the EU.

PMID- 29582761
TI  - Post-exposure prophylaxis in Ebola virus disease: don't forget the psychological
      factors.

PMID- 29582762
TI  - The fourth HIV epidemic.

PMID- 29582763
TI  - Hepatitis C virus treatment as prevention in people who inject drugs.

PMID- 29582764
TI  - Extended infusion-putting the benefit into context.

PMID- 29582765
TI  - Reassessing the 1 + 1 pneumococcal conjugate vaccine schedule.

PMID- 29582766
TI  - Reassessing the 1 + 1 pneumococcal conjugate vaccine schedule - Authors' reply.

PMID- 29582767
TI  - Reassessing the 1 + 1 pneumococcal conjugate vaccine schedule.

PMID- 29582768
TI  - New clinical recommendations for Clostridium difficile.

PMID- 29582772
TI  - Kit Fairley: a pioneer in STI research.

PMID- 29582769
TI  - Known unknowns and unknown unknowns.

PMID- 29582773
TI  - Streptococcus pyogenes subdural empyema and pre-eclampsia.

PMID- 29582774
TI  - Plastic bronchitis associated with adenovirus infection.

PMID- 29582775
TI  - Highly piezoelectric BaTiO3 nanorod bundle arrays using epitaxially grown TiO2
      nanomaterials.
AB  - Low-dimensional piezoelectric nanostructures such as nanoparticles, nanotubes,
      nanowires, nanoribbons and nanosheets have been developed for potential
      applications as energy harvesters, tunable sensors, functional transducers and
      low-power actuators. In this study, lead-free BaTiO 3 nanorod bundle arrays (NBA)
      with highly piezoelectric properties were successfully synthesized on fluorine
      doped tin oxide (FTO) substrate via a two-step process consisting of TiO2
      epitaxial growth and BaTiO3 conversion. Through the TiO2 epitaxial growth on FTO
      substrate, (001) oriented TiO2 nanostructures formed vertically-aligned NBA with
      a bundle diameter of 80 nm and an aspect ratio of six. In particular, chemical
      etching of the TiO2 NBA was conducted to enlarge the surface area for effective
      Ba2+ ion diffusion during the perovskite conversion process from TiO2 to BaTiO3.
      The final structure of perovskite BaTiO3 NBA was found to exhibit a feasible
      piezoelectric response of 3.56 nm with a clear phase change of 180 degrees  from
      the single BaTiO3 bundle, by point piezoelectric forced microscopy (PFM)
      analysis. Consequently, highly piezoelectric NBA could be a promising
      nanostructure for various nanoscale electronic devices.

PMID- 29582776
TI  - A comparative study on top-gated and bottom-gated multilayer MoS2 transistors
      with gate stacked dielectric of Al2O3/HfO2.
AB  - Top-gated and bottom-gated transistors with multilayer MoS2 channel fully
      encapsulated by stacked Al2O3/HfO2 (9 nm/6 nm) were fabricated and comparatively
      studied. Excellent electrical properties are demonstrated for the TG transistors
      with high on-off current ratio of 108, high field-effect mobility of 102 cm2 V-1
      s-1, and low subthreshold swing of 93 mV dec-1. Also, enhanced reliability has
      been achieved for the TG transistors with threshold voltage shift of 10-3-10-2 V
      MV-1 cm-1 after 6 MV cm-1 gate-biased stressing. All improvement for the TG
      device can be ascribed to the formed device structure and dielectric environment.
      Degradation of the performance for the BG transistors should be attributed to
      reduced gate capacitance density and deteriorated interface properties related to
      vdW gap with a thickness about 0.4 nm. So, the TG transistor with MoS2 channel
      fully encapsulated by stacked Al2O3/HfO2 is a promising way to fabricate high
      performance ML MoS2 field-effect transistors for practical electron device
      applications.

PMID- 29582777
TI  - A simple bipedal model for studying control of gait termination.
AB  - We study the control of human gait termination with a simple bipedal locomotion
      model. Several control strategies have been proposed for gait termination.
      However, the relative importance of these strategies has not been evaluated in
      models of human gait. Here we extend the bipedal spring mass walking model in a
      least parameter fashion and study three explicit control strategies for gait
      termination, including the shortening of the final step, braking at the ankle,
      and extending the knee. Applying the strategies separately, we find that only
      braking at the ankle reduces the propulsive force enough to transition into quiet
      standing. In combination with the other two strategies, we observe that the range
      of control parameters suitable for gait termination increases, especially when
      the ankle control is applied intermittently by taking advantage of passive
      stabilizing dynamics. We further show the resulting model behavior is compatible
      with several experimental observations about the human center of mass dynamics
      and leg forces during gait termination, and discuss model improvements to correct
      mismatches. The proposed model may serve as a starting point for more advanced
      models that can provide a deeper understanding of human control strategies during
      gait termination.

PMID- 29582778
TI  - Highly improved ethanol gas-sensing performance of mesoporous nickel oxides
      nanowires with the stannum donor doping.
AB  - Mesoporous nickel oxides (NiO) and stannum(Sn)-doped NiO nanowires (NWs) were
      synthesized by using SBA-15 templates with the nanocasting method. X-ray
      diffraction, transmission electron microscope, energy dispersive spectrometry,
      nitrogen adsorption/desorption isotherm and UV-vis spectrum were used to
      characterize the phase structure, components and microstructure of the as
      prepared samples. The gas-sensing analysis indicated that the Sn-doping could
      greatly improve the ethanol sensitivity for mesoporous NiO NWs. With the
      increasing Sn content, the ethanol sensitivity increased from 2.16 for NiO NWs up
      to the maximum of 15.60 for Ni0.962Sn0.038O1.038, and then decreased to 12.24 for
      Ni0.946Sn0.054O1.054 to 100 ppm ethanol gas at 340  degrees C. The high surface
      area from the Sn-doping improved the adsorption of oxygen on the surface of NiO
      NWs, resulting in the smaller surface resistance in air. Furthermore, owing to
      the recombination of the holes in hole-accumulation lay with the electrons from
      the donor impurity level and the increasing the body defects for Sn-doping, the
      total resistance in ethanol gas enhanced greatly. It was concluded that the
      sensitivity of Sn-doped NiO NWs based sensor could be greatly improved by the
      higher surface area and high-valence donor substitution from Sn-doping.

PMID- 29582779
TI  - Immobilized Pd-Ag bimetallic nanoparticles on polymeric nanofibers as an
      effective catalyst: effective loading of Ag with bimetallic functionality through
      Pd nucleated nanofibers.
AB  - Here, we present a precise process for synthesizing Pd-Ag bimetallic
      nanoparticles (NPs) onto polymeric nanofibers by decorating Pd-NPs through atomic
      layer deposition followed by a chemical reduction process for tagging Ag
      nanostructures with bimetallic functionality. The results show that Pd-NPs act as
      a nucleation platform for tagging Ag and form Pd-Ag bimetallic NPs with a
      monodisperse nature with significant catalytic enhancement to the reaction rate
      over the bimetallic nature of the Pd-Ag ratio. A Pd-NP decorated polymeric
      nanofibrous web acts as an excellent platform for the encapsulation or
      interaction of Ag, which prevents agglomeration and promotes the interaction of
      Ag ions only on the surface of the Pd-NPs. We observed an effective reduction of
      4-nitrophenol (4-NP) to 4-aminophenol (4-AP) by sodium borohydride (NaBH4) to
      access the catalytic activity of Pd-Ag bimetallic NPs on a free-standing flexible
      polymeric nanofibrous web as a support. The captive formation of the polymeric
      nanofibrous web with Pd-Ag bimetallic functionality exhibited superior and stable
      catalytic performance with reduction rates of 0.0719, 0.1520, and 0.0871 min-1
      for different loadings of Ag on Pd decorated nanofibrous webs such as
      Pd/Ag(0.01), Pd/Ag(0.03), and Pd/Ag(0.05), respectively. The highly faceted Pd-Ag
      NPs with an immobilized nature improves the catalytic functionality by enhancing
      the binding energy of the 4-NP adsorbate to the surface of the NPs. With the aid
      of bimetallic functionality, the nanofibrous web was demonstrated as a hybrid
      heterogeneous photocatalyst with a 3.16-fold enhancement in the reaction rate as
      compared with the monometallic decorative nature of NaBH4 as a reducing agent.
      The effective role of the monodisperse nature of Pd ions with an ultralow content
      as low as 3 wt% and the tunable ratio of Ag on the nanofibrous web induced
      effective catalytic activity over multiple cycles.

PMID- 29582780
TI  - MR-compatibility assessment of MADPET4: a study of interferences between an SiPM
      based PET insert and a 7 T MRI system.
AB  - Compromises in the design of a positron emission tomography (PET) insert for a
      magnetic resonance imaging (MRI) system should minimize the deterioration of
      image quality in both modalities, particularly when simultaneous demanding
      acquisitions are performed. In this work, the advantages of using individually
      read-out crystals with high-gain silicon photomultipliers (SiPMs) were studied
      with a small animal PET insert for a 7 T MRI system, in which the SiPM charge was
      transferred to outside the MRI scanner using coaxial cables. The interferences
      between the two systems were studied with three radio-frequency (RF) coil
      configurations. The effects of PET on the static magnetic field, flip angle
      distribution, RF noise, and image quality of various MRI sequences (gradient
      echo, spin echo, and echo planar imaging (EPI) at 1H frequency, and chemical
      shift imaging at 13C frequency) were investigated. The effects of fast-switching
      gradient fields and RF pulses on PET count rate were studied, while the PET
      insert and the readout electronics were not shielded. Operating the insert inside
      a 1H volume coil, used for RF transmission and reception, limited the MRI to T1
      weighted imaging, due to coil detuning and RF attenuation, and resulted in
      significant PET count loss. Using a surface receive coil allowed all tested MR
      sequences to be used with the insert, with 45-59% signal-to-noise ratio (SNR)
      degradation, compared to without PET. With a 1H/13C volume coil inside the insert
      and shielded by a copper tube, the SNR degradation was limited to 23-30% with all
      tested sequences. The insert did not introduce any discernible distortions into
      images of two tested EPI sequences. Use of truncated sinc shaped RF excitation
      pulses and gradient field switching had negligible effects on PET count rate.
      However, PET count rate was substantially affected by high-power RF block pulses
      and temperature variations due to high gradient duty cycles.

PMID- 29582781
TI  - Objective profiling of varied human motion based on normative assessment of
      magnetometer time series data.
AB  - OBJECTIVE: To quantify varied human motion and obtain an objective assessment of
      relative performance across a cohort. APPROACH: A wrist-worn magnetometer was
      used to record and quantify the complex motion patterns of 55 children aged 10 to
      12 years old, generated during a fundamental movement skills programme. Sensor
      based quantification of the physical activity used dynamic time warping of the
      magnetometer time series data for pairs of children. Pairwise comparison across
      the whole cohort produced a similarity matrix of all child to child correlations.
      Normative assessment scores were based on the Euclidean distance between n
      participants within an n  -  1 multi-variate space, created from multi
      dimensional scaling of the similarity matrix. The sensor-based scores were
      compared to the current standardised assessment which involves binary scoring of
      technique, outcome and time components by trained assessors. MAIN RESULTS:
      Visualisation of the relative performance using the first three axes of the multi
      dimensional matrix, shows a 'performance sphere' in which children sit on
      concentric shells of increasing radius as performance deteriorates. Good
      agreement between standard and sensor scores is found, with Spearman rank
      correlation coefficients of the overall activity score in the range of 0.62-0.71
      for different cohorts and a kappa statistic of 0.34 for categorisation of all 55
      children into lower, middle, upper tertile and top 5% bands. SIGNIFICANCE: By
      using multi-dimensional analysis of similarity measures between participants
      rather than direct parameterisation of the physiological data, complex and varied
      patterns of physical motion can be quantified, allowing objective and robust
      profiling of relative function across participant groups.

PMID- 29582782
TI  - QMCPACK: an open source ab initio quantum Monte Carlo package for the electronic
      structure of atoms, molecules and solids.
AB  - QMCPACK is an open source quantum Monte Carlo package for ab initio electronic
      structure calculations. It supports calculations of metallic and insulating
      solids, molecules, atoms, and some model Hamiltonians. Implemented real space
      quantum Monte Carlo algorithms include variational, diffusion, and reptation
      Monte Carlo. QMCPACK uses Slater-Jastrow type trial wavefunctions in conjunction
      with a sophisticated optimizer capable of optimizing tens of thousands of
      parameters. The orbital space auxiliary-field quantum Monte Carlo method is also
      implemented, enabling cross validation between different highly accurate methods.
      The code is specifically optimized for calculations with large numbers of
      electrons on the latest high performance computing architectures, including
      multicore central processing unit and graphical processing unit systems. We
      detail the program's capabilities, outline its structure, and give examples of
      its use in current research calculations. The package is available at
      http://qmcpack.org.

PMID- 29582783
TI  - Modulation of the photoluminescence in carbon dots through surface modification:
      from mechanism to white light-emitting diodes.
AB  - Carbon dots (CDs) have emerged as a new type of fluorescent material because of
      their unique optical advantages, such as high photoluminescence quantum yields
      (QYs), excellent photo-stability, excitation-dependent emissions, and low
      toxicity. However, the photoluminescence mechanism for CDs remains unclear, which
      limits their further practical application. Here, CDs were synthesized via a
      solvothermal route from citric acid and urea. Through the oxidation and reduction
      treatment of pristine CDs, the origin of the photoluminescence and the involved
      mechanism were revealed. We found that the blue/green/red emissions originated
      from three diverse emitting states, i.e. the intrinsic state, and C=O- and C=N
      related surface states, respectively. Based on the as-prepared CDs, a pH sensor
      depending on the radiometric luminescence detection was developed. Furthermore,
      we constructed CD/PVP (PVP, polyvinylpyrrolidone) composite films, which
      exhibited white light emission with photoluminescence QYs of 15.3%. The white
      light emission with different correlated color temperatures (CCTs), from 4807 K
      to 3319 K, was obtained by simply changing the amount of PVP solution. Benefiting
      from the white light-emitting solid-state films, single-component white light
      emitting diodes were fabricated with an average color rendering index value (Ra)
      of 80.0, luminous efficiency of 10.2 lm W-1, and good working stability, thus
      indicating a promising potential for practical lighting applications.

PMID- 29582784
TI  - Bias-switchable negative and positive photoconductivity in 2D FePS3 ultraviolet
      photodetectors.
AB  - Metal-phosphorus-trichalcogenides (MPTs), represented by NiPS3, FePS3, etc, are
      newly developed 2D wide-bandgap semiconductors and have been proposed as
      excellent candidates for ultraviolet (UV) optoelectronics. In spite of having
      superior advantages for solar-blind UV photodetectors, including those free of
      surface trap states, being highly compatible with versatile integrations as well
      as having an appropriate band gap, to date relevant study is rare. In this work,
      the photoresponse characteristic of UV detectors based on few-layer FePS3 has
      been comprehensively investigated. The responsivity of the photodetector, which
      is observed to be determined by bias gate voltage, may achieve as high as 171.6
      mAW-1 under the illumination of 254 nm weak light, which is comparable to most
      commercial UV detectors. Notably, both negative and positive photoconductivities
      exist in the FePS3 photodetectors and can be controllably switched with bias
      voltage. The eminent and novel photoresponse property paves the way for the
      further development and practical use of 2D MPTs in high-performance UV
      photodetections.

PMID- 29582786
TI  - Surface wave energy absorption by a partially submerged bio-inspired canopy.
AB  - Aquatic plants are known to protect coastlines and riverbeds from erosion by
      damping waves and fluid flow. These flexible structures absorb the fluid-borne
      energy of an incoming fluid by deforming mechanically. In this paper we focus on
      the mechanisms involved in these fluid-elasticity interactions, as an efficient
      energy harvesting system, using an experimental canopy model in a wave tank. We
      study an array of partially-submerged flexible structures that are subjected to
      the action of a surface wave field, investigating in particular the role of
      spacing between the elements of the array on the ability of our system to absorb
      energy from the flow. The energy absorption potential of the canopy model is
      examined using global wave height measurements for the wave field and local
      measurements of the elastic energy based on the kinematics of each element of the
      canopy. We study different canopy arrays and show in particular that flexibility
      improves wave damping by around 40%, for which half is potentially harvestable.

PMID- 29582785
TI  - Impact of anti-charge sharing on the zero-frequency detective quantum efficiency
      of CdTe-based photon counting detector system: cascaded systems analysis and
      experimental validation.
AB  - Inter-pixel communication and anti-charge sharing (ACS) technologies have been
      introduced to photon counting detector (PCD) systems to address the undesirable
      charge sharing problem. In addition to improving the energy resolution of PCD,
      ACS may also influence other aspects of PCD performance such as detector
      multiplicity (i.e. the number of pixels triggered by each interacted photon) and
      detective quantum efficiency (DQE). In this work, a theoretical model was
      developed to address how ACS impacts the multiplicity and zero-frequency DQE
      [DQE(0)] of PCD systems. The work focused on cadmium telluride (CdTe)-based PCD
      that often involves the generation and transport of K-fluorescence photons. Under
      the parallel cascaded systems analysis framework, the theory takes both
      photoelectric and scattering effects into account, and it also considers both the
      reabsorption and escape of photons. In a new theoretical treatment of ACS, it was
      considered as a modified version of the conventional single pixel (i.e. non-ACS)
      mode, but with reduced charge spreading distance and K-fluorescence travel
      distance. The proposed theoretical model does not require prior knowledge of the
      detailed ACS implementation method for each specific PCD, and its parameters can
      be experimentally determined using a radioisotope without invoking any Monte
      Carlo simulation. After determining the model parameters, independent validation
      experiments were performed using a diagnostic x-ray tube and four different
      polychromatic beams (from 50 to 120 kVp). Both the theoretical and experimental
      results demonstrate that ACS increased the first and second moments of
      multiplicity for a majority of the x-ray energy and threshold levels tested,
      except when the threshold level was much lower than the x-ray energy level.
      However, ACS always improved DQE(0) at all energy and threshold levels tested.

PMID- 29582787
TI  - Association between human leukocyte antigen-DRB1 and human leukocyte antigen-DQB1
      alleles and pemphigus vulgaris in Indian patients: A case-control study.
AB  - Background: HLA-DRB1*04, -DRB1*08, -DRB1*14, -DQB1*03 and -DQB1*05 are reported
      to have significant association with pemphigus vulgaris; however, this is
      partially dependent on ethnicity. This study was done to determine the HLA-DR and
      -DQ types prevalent in Indian patients with pemphigus vulgaris. Methods: A
      prospective case-control study was done for a period of 9 months in Christian
      Medical College Vellore, India. HLA typing was done by PCR-SSOP method in 50
      cases and 50 healthy controls. Allele frequencies in cases and controls were
      compared and odds ratios with 95% confidence interval were calculated. Results:
      The mean age of the patients (29 females, 21 males) and that of controls (36
      males, 14 females) were 41.3 +/- 13.65 and 35.42 +/- 11.09 years, respectively.
      HLA-DRB1*14 was present in 47 patients and 18 controls (OR, 27.85; 95% CI, 7.57
      102.42) and HLA-DQB1*05 was seen in 47 patients and 24 controls (OR, 16.97; 95%
      CI, 4.66-61.80). The haplotype DRB1*14, DQB1*05 was present in 44 patients and 14
      controls (OR, 18.86; 95% CI, 6.58-54.05). DRB1*15 was present in 7 cases and 16
      controls (OR, 0.35; 95% CI, 0.13-0.94) and DQB1*06 was present in 8 cases and 19
      controls (OR, 0.31; 95% CI, 0.12-0.80). HLA-DQB1*03 was associated with
      significantly higher pemphigus disease area index scores. Limitations: The main
      limitations were that the numbers studied were small as the study was conducted
      at a single center, and the haplotype analysis was limited only to the proband.
      PDAI scores could have been influenced by prior treatment. Conclusion: There was
      a significant association between HLA-DRB1*14 and HLA-DQB1*05 and pemphigus
      vulgaris in our patients. A negative association was seen with DRB1*15 and
      DQB1*06.

PMID- 29582788
TI  - Solitary nodular lesion on forehead in a 56-year-old woman.

PMID- 29582789
TI  - Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.
AB  - BACKGROUND: Alopecia areata is an immune-dependent disorder characterized by the
      interaction of T-lymphocytes with follicular antigens. Recent studies have shown
      the existence of a local renin-angiotensin system in the skin, where angiotensin
      converting enzyme (ACE) plays a role in autoimmunity and inflammation. AIM: The
      objective of this study was to evaluate serum and tissue ACE activity in patients
      with alopecia areata. METHODS: This case-control study was conducted on patients
      with alopecia areata and healthy controls. Serum and tissue ACE activity were
      assessed and compared between the two groups. RESULTS: Twenty-five alopecia
      areata patients (60% male, mean age 32.1 +/- 9.9 years) and 24 controls (50%
      male, mean age 37.4 +/- 8.8 years) were included. Mean serum ACE activity was
      52.1 +/- 9 U/L in cases and 55.3 +/- 14.7 U/L in controls (P = 0.37). Tissue ACE
      activity was significantly lower in cases in all parts of the skin i.e. epidermis
      (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037).
      Among cases, serum ACE activity was significantly higher in patients with more
      severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis;
      ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P
      = 0.027). LIMITATIONS: The sample size was too small to draw definite
      conclusions. Further, most of the patients had only mild or moderate alopecia
      areata. CONCLUSION: Unlike in some other inflammatory diseases, the tissue level
      of ACE seems to be significantly lower in alopecia areata compared to normal
      controls. Serum ACE was significantly higher in patients with more severe
      disease.

PMID- 29582790
TI  - Papillary eccrine adenoma associated with syringocystadenoma papilliferum.

PMID- 29582791
TI  - A case of cutaneous focal bilirubin deposition in a man with jaundice.

PMID- 29582792
TI  - Perspectives on the clinical development of immunotherapy in prostate cancer.
AB  - Despite impressive survival benefits with immunotherapy in patients with various
      solid tumors, the full potential of these agents in prostate cancer has yet to be
      realized. Sipuleucel-T demonstrated a survival benefit in this population,
      indicating that prostate cancer is an immunoresponsive disease; however, these
      results have not been matched by other agents. A large trial with ipilimumab in
      prostate cancer failed to meet its primary objective, and small trials with PD
      1/PD-L1 inhibitors did not yield a significant improvement in overall response.
      However, several late-stage clinical trials are underway with other vaccines in
      prostate cancer. Reports of clinical benefit with immunotherapies, particularly
      when used in combination or a select population, have provided the framework to
      develop sound clinical trials. Understanding immunogenic modulation, antigen
      spread, biomarkers, and DNA-repair defects will also help mold future strategies.
      Through rational patient selection and evidence-based combination approaches,
      patients with prostate cancer may soon derive durable survival benefits with
      immunotherapies.

PMID- 29582793
TI  - Laparoscopic ventral rectopexy: A viable option in procidentia with redundant
      sigmoid - An Indian perspective.
AB  - Introduction: Laparoscopic ventral mesh rectopexy (LVMR) has gained widespread
      acceptance for the management of complete rectal prolapse (CRP). However, there
      have been concerns considering its use in patients with a redundant sigmoid
      colon. This study was conducted to evaluate the anatomical and functional results
      following LVMR, particularly in cases of CRP with a redundant sigmoid colon.
      Materials and Methods: Retrospective analysis of 25 patients who underwent LVMR
      from January 2011 to September 2016 was performed. Patients were divided into two
      groups according to the duration of follow-up. Group A (long-term) with follow-up
      >3 years and Group B (mid-term) <3 years. Results: The study included 25 patients
      (M:F = 1.5:1) with a median age of 38 years. Eighty-eight percent of the patients
      had a redundant sigmoid colon. Significant improvement in post-operative Wexner
      score as compared to pre-operative values was seen in patients with pre-existing
      constipation (P < 0.0001). In patients presenting with faecal incontinence (FI),
      significant improvement in post-operative St. Mark's incontinence score was
      observed. Functional outcomes remain consistent in long-term follow-up (>3
      years). Conclusions: LVMR seems to be a feasible surgical procedure with minimum
      morbidity and good long-term functional outcomes. It provides satisfactory
      results in patients with redundant sigmoid colon and improves pre-existing
      constipation and FI.

PMID- 29582794
TI  - Application of a newly designed microfork probe for robotic-guided pelvic
      intraoperative neuromapping.
AB  - INTRODUCTION: Robotic-assisted total mesorectal excision (TME) with pelvic
      intraoperative neuromapping was recently accomplished. However, neuromapping is
      conventionally conducted by a hand-guided laparoscopic probe. We introduce a
      prototype microfork probe to make robotic-guided neuromapping feasible.
      Experiments and Technical Setup: Two porcine experiments with nerve-sparing TME
      surgery were performed. A newly designed prototype bipolar microfork probe was
      inserted intraabdominally and guided with the robotic forceps. Intermittent
      neuromapping was then conducted and neuromonitoring data integrated in the
      surgeon console viewer. CONCLUSION: Robotic-guided neuromapping is shown to be
      feasible and fully controllable from the surgeon console.

PMID- 29582796
TI  - Prospective analysis of laparoscopic versus open radical nephrectomy for renal
      tumours more than 7 cm.
AB  - Aims: To analyse the feasibility of laparoscopic radical nephrectomy (LRN) for
      renal tumours >7 cm and to compare the operative and oncologic outcomes with open
      radical nephrectomy (ORN). Settings and Design: This was a prospective,
      observational, comparative study. Subjects and Methods: The study was conducted
      at a tertiary care super-speciality hospital. All the patients who underwent
      radical nephrectomy for >7 cm renal tumours during a period of 2 years (April
      2012 to May 2014) were included in the study. Thirty patients were included in
      each ORN and LRN group. Pre-operative, intra-operative and post-operative data
      for all these patients were collected and analysed. Statistical Analysis Used:
      Statistical Package for the Social Sciences (SPSS, version 11.0 for Windows,
      Chicago, IL). Results: Mean age of patients in ORN and LRN groups was 57.3 +/-
      6.1 years and 54.9 +/- 5.7 years, respectively (P = 0.220). As compared to ORN,
      LRN had less drop in post-operative haemoglobin (1.39 +/- 0.55 g/dl vs. 4.07 +/-
      1.023 g/dl, P < 0.05), less drop in haematocrit value (4.7 +/- 3.25% vs. 9.5 +/-
      5.13%, P < 0.05), less analgesic requirement for tramadol hydrochloride (165 +/-
      74.5 mg vs. 260 +/- 181.66 mg) and less mean hospital stay (4.2 days vs. 6.1
      days, P < 0.05). There was no statistically significant difference in post
      operative complication rate and recurrence-free survival over a median follow-up
      of 17 months (93.9% - LRN vs. 90% - ORN). Conclusions: LRN for large renal
      tumours is feasible and achieves oncologic outcomes similar to that obtained with
      ORN.

PMID- 29582795
TI  - Laparoscopic Nissen fundoplication: The effects of high-concentration
      supplemental perioperative oxygen on the inflammatory and immune response: A
      randomised controlled trial.
AB  - Background: A number of studies have been reported on the effects of high
      concentration oxygen (HCO) on cytokine synthesis, with controversial results. We
      assessed the effect of administration of perioperative HCO on systemic
      inflammatory and immune response in patients undergoing laparoscopic Nissen
      fundoplication (LNF). Materials and Methods: Patients (n = 117) were assigned
      randomly to an oxygen/air mixture with a fraction of inspired oxygen (FiO2) of
      30% (n = 58) or 80% (n = 59). Administration was commenced after induction of
      anaesthesia and maintained for 6 h after surgery. White blood cells, peripheral
      lymphocytes subpopulation, human leucocyte antigen-DR (HLA-DR), neutrophil
      elastase, interleukin (IL)-1 and IL-6 and C-reactive protein (CRP) were
      investigated. Results: A significantly higher concentration of neutrophil
      elastase, IL-1, IL-6 and CRP was detected post-operatively in the 30% FiO2group
      patients in comparison with the 80% FiO2group (P < 0.05). A statistically
      significant change in HLA-DR expression was recorded post-operatively at 24 h, as
      a reduction of this antigen expressed on monocyte surface in patients from 30%
      FiO2group; no changes were noted in 80% FiO2group (P < 0.05). Conclusions: This
      study demonstrated that perioperative HCO (80%), during LNF, can lead to a
      reduction in post-operative inflammatory response, and possibly, avoid post
      operative immunosuppression.

PMID- 29582797
TI  - Rescue stitch: A minimal access surgeon's lifeboat in life-threatening
      intraoperative bleeding.
AB  - Bleeding in a minimal access surgery can be very intimidating for a laparoscopic
      surgeon. Open conversion becomes an imminent option in these situations. Although
      open conversion is not a surgical defeat, in certain situations, bleeding can be
      salvaged using a 'rescue stitch.' We, herein, describe rescue stitch along with a
      rescue tray and its application during intraoperative bleeding in minimal access
      surgery.

PMID- 29582798
TI  - Our experience of laparoscopic pyloromyotomy with ultrasound-guided parameters.
AB  - Traditional management of infantile Hypertrophic Pyloric Stenosis is open
      pyloromyotomy after initial adequate resuscitation of the patient. From 1991,
      laparoscopic approach is considered feasible and safe. Today, diagnosis of
      hypertrophic pyloric stenosis is made most often made by ultrasound. With use of
      ultrasound-guided parameters (length of pyloric tumour and thickness of pyloric
      tumour), we could avoid 'incomplete pyloromyotomy' and 'mucosal perforation'
      (most common complications in laparoscopic approach) to achieve 100% adequacy and
      safety in laparoscopic pyloromyotomy.

PMID- 29582799
TI  - Laparoscopic hysterectomy for large uteri: Outcomes and techniques.
AB  - Aim: The aim of this study was to analyse our data of laparoscopic hysterectomy
      for large uteri (>16 weeks size) regarding their perioperative outcomes and
      possible factors for conversions to open surgery over 5 years. It also describes
      our techniques for the feasibility of performing such hysterectomies by the
      minimally invasive way. Materials and Methods: A five-year retrospective chart
      review was performed at the Minimal Access and Robotic Surgery Unit of the
      Department of Gynecology at Apollo Hospital, Hyderabad. Demographic and pre
      operative and post-operative data were recorded. Clinical assessment including
      bimanual examination and surgery was made by a single senior surgeon. Intra
      operative conversions, complications and post-operative complications were
      recorded. Results: A total of 128 women were included in this study, 5 patients
      underwent robotic-assisted hysterectomy. The average age was 44.4, body mass
      index - was 27.6 and size of the uterus was 17.5 weeks. The most common diagnosis
      was leiomyoma. The median Operating room (OR) time was 107 min. There was a need
      for myomectomy in 39.8%, extensive adhesiolysis in 33.6% and dense bladder
      adhesion in 26.6%. The average drop in haemoglobin was 1.72 g%, and hospital stay
      was 2 days. The specimen was removed by vaginal morcellation (2 cases via an
      umbilical port). Conversion to open surgery was required in 10.9% of cases. The
      conversion was significantly correlated with excessive haemorrhage and bladder
      injury but not with difficult hysterectomy, difficult bladder dissection or
      adhesions. There were 3 cases of bladder injury detected and managed
      intraoperatively. Conclusion: Laparoscopic hysterectomy is technically feasible
      and safe procedure for large uteri. The learning curve is about 50 cases and can
      be performed by experienced surgeons regardless of the size, number or location
      of the myomas without much morbidity.

PMID- 29582800
TI  - Laparoscopic retromuscular incisional hernia repair.
AB  - A 67-year-old male with a history of a conventional right colectomy and
      hypertension was referred to our department for an incisional hernia and
      abdominal discomfort. Physical examination also showed a supraumbilical defect
      that was confirmed with a computed tomography scan. Laparoscopic Rives technique
      repair was done to repair the defect avoiding direct contact of the mesh with the
      intra-abdominal viscera.

PMID- 29582801
TI  - Short-term outcomes of minimally invasive surgery for patients presenting with
      suspected gallbladder cancer: Report of 8 cases.
AB  - INTRODUCTION: Minimally invasive surgery (MIS) for gallbladder cancer (GBCa) has
      traditionally been discouraged, with limited studies reporting on its outcomes.
      The aim of this study was to evaluate the short-term outcomes of MIS for patients
      with GBCa or suspected GBCa. METHODS: A retrospective study of 8 consecutive
      patients who underwent MIS for GBCa by a single surgeon over a 22-month period
      between 2015 and 2017. RESULTS: Three patients underwent robotic surgery, while
      five underwent conventional laparoscopic surgery. Four patients presented with
      histologically proven GbCa detected incidentally after cholecystectomy. All 4
      patients underwent resection of Segment 4b/5. Of these, 3 underwent hilar
      lymphadenectomy and 1 underwent hilar lymph node sampling. Four patients
      presenting with suspected GBCa underwent upfront extended cholecystectomy. Two
      patients who had malignancy on frozen section underwent hilar lymphadenectomy.
      The median operation time was 242.5 (range, 165-530) min, and the median blood
      loss was 175 (range, 50-700) ml. The median post-operative hospital stay was 3.5
      (range, 2-8) days. There were no open conversion, post-operative morbidities and
      mortalities. Six had histologically proven GBCa. Five were T3 and one had T2
      cancers. CONCLUSIONS: The results of the present study confirm the short-term
      safety and feasibility of MIS for patients with GBCa, as all eight patients
      underwent successful MIS with no major morbidity or mortality. Further studies
      with larger patient cohorts with long-term follow-up are needed to determine the
      oncologic outcomes and the definitive role of MIS in treating GBCa.

PMID- 29582802
TI  - The surgical outcome of minimally invasive pharyngo-laryngo-oesophagectomy in
      prone position.
AB  - PURPOSE: Pharyngo-laryngo-oesophagectomy (PLE) which is mainly indicated for
      cervical oesophageal cancer or synchronous double cancer of the thoracic
      oesophagus and the pharynx or larynx, is extremely invasive. Since minimally
      invasive oesophagectomy (MIE) using video-assisted thoracic surgery has become
      popular recently, the procedure can be adopted to PLE. Moreover, the use of the
      prone position (PP) in MIEs has been increasing recently because technical
      advantages and fewer post-operative complications were reported. To assess the
      validity of PP, this study compared surgical outcomes of minimally invasive PLE
      (MIPLE) in PP with that in the left lateral decubitus position (LLDP). PATIENTS
      AND METHODS: This study enrolled consecutive 15 patients that underwent MIPLE
      with LLDP (n = 7) or PP (n = 8) between January 1996 and October 2016. The
      patients' background characteristics, operative findings and post-operative
      complications were examined. RESULTS: Eligible diseases are 5 cases of cervical
      oesophageal cancer, 9 cases of synchronous double cancer of the thoracic
      oesophagus and head and neck and 1 case of cervical oesophageal recurrence of the
      head-and-neck cancer. The patients' background characteristics were not
      significantly different. During surgery, thoracic blood loss was significantly
      lower in PP than in LLDP (P = 0.0487). Other operative findings and post
      operative complications were not significantly different between the two groups.
      CONCLUSIONS: In MIPLE, the PP could reduce blood loss due to the two-lung
      ventilation under artificial pneumothorax and was associated with lower surgical
      stress than LLDP.

PMID- 29582803
TI  - Management of portal annular pancreas during laparoscopic
      pancreaticoduodenectomy.
AB  - Portal annular pancreas (PAP) is a pancreatic congenital anomaly consisting of
      pancreatic parenchyma encircling the portal vein and/or the superior mesenteric
      vein. It has been reported that the risk of developing a post-operative
      pancreatic fistula is higher following pancreaticoduodenectomy in patients with
      PAP, probably because of the possibility of leaving undrained a portion of
      pancreatic parenchyma during the reconstructive phase. Few manuscripts have
      reported a surgical technique of pancreaticoduodenectomy in case of PAP, herein
      we report the first case of a patient with PAP undergoing laparoscopic
      pancreaticoduodenectomy.

PMID- 29582804
TI  - Laparoscopic repair for parastomal hernia with ongoing barbed suture followed by
      sandwich-technique: 'Sandwich-plus-technique'.
AB  - The incidence of parastomal hernias after a permanent stoma is between 50% and
      80% depending on the type of stoma, the definition of the hernia (clinical or
      radiological), and the length of the follow-up. Surgical therapy is complex and
      involves several techniques with different recurrence rates. We present three
      cases where we have closed the hernia gap with continuous, non-resorbable, self
      retaining sutures with subsequent use of the sandwich technique ('Sandwich-plus
      technique'). There were pronounced parastomal hernias in three female patients
      (mean age was 72 years and the range was 63-78 years) with permanent colostomata.
      After laparoscopic adhesiolysis, the closure of the hernia defect was completed
      with ongoing, barbed non-resorbable 1-0 sutures (polybutester) followed by the
      sandwich technique. There were no intraoperative complications and currently no
      clinical or radiological evidence for recurrences of the parastomal hernia.
      Closure of the hernia gap leads to the additional reconstruction of the lateral
      abdominal wall, resulting in a larger contact surface for integration of the
      keyhole mesh and thus prior to implantation of the Sugarbaker mesh. The
      laparoscopic augmentation of large parastomal hernias using the 'Sandwich-plus
      technique' is technically complex but achieves very good results in our case
      series. Further studies and long-term results should prove that the low
      recurrence rate of the sandwich technique can be further reduced.

PMID- 29582805
TI  - Brace up or burnout.

PMID- 29582806
TI  - Evaluation of macular ganglion cell analysis compared to retinal nerve fiber
      layer thickness for pre-perimetric glaucoma diagnosis.

PMID- 29582807
TI  - Rings on the eyes, matters of the heart.

PMID- 29582809
TI  - Concomitant use of conjunctival tissue graft from the pterygium itself without
      rotation in pterygium surgery: A full circle in conjunctival autografting.
AB  - Purpose: The aim of this study is to describe a modified technique of using
      conjunctival tissue from the pterygium itself without any rotation of graft for
      the primary pterygium in eyes with glaucoma filtering bleb, glaucoma suspects,
      and in primary double-head pterygium using fibrin glue. Methods: In this
      retrospective, noncomparative, interventional case series, 98 eyes of 98 patients
      with primary pterygium operated between July 2011 to July 2016 were included.
      They underwent this technique from the pterygium tissue itself. There was no
      rotation of this graft, and it was adhered to the bare scleral defect with fibrin
      glue. Histopathological analysis of pterygium tissue was done to look for
      morphology and thickness of this thin conjunctival tissue obtained from pterygium
      tissue itself. The primary outcome measure was recurrence rate. Other outcome
      measures studied was graft retraction and graft edema. Results: The mean age was
      52 +/- 10.04 years. Mean follow-up was 14 +/- 8.24 months. The only significant
      complication was recurrence rate of 4.08% (4 eyes out of 98). The most come
      secondary outcome was graft edema, 52.04% (51 eyes out of 98) which resolved
      without any intervention. Other outcome such as graft retraction, 32.65% was also
      recorded. Conclusion: Conjunctival tissue from the pterygium tissue itself
      without actual rotation appears to be a successful technique with lower
      recurrence rate for treating primary pterygium in eyes with glaucoma filtering
      bleb, glaucoma suspects, and in primary double-head pterygium.

PMID- 29582808
TI  - Simplifying "target" intraocular pressure for different stages of primary open
      angle glaucoma and primary angle-closure glaucoma.
AB  - Lowering of intraocular pressure is currently the only therapeutic measure for
      Glaucoma management. Many longterm, randomized trials have shown the efficacy of
      lowering IOP, either by a percentage of baseline, or to a specified level. This
      has lead to the concept of 'Target" IOP, a range of IOP on therapy, that would
      stabilize the Glaucoma/prevent further visual field loss, without significantly
      affecting a patient's quality of life. A clinical staging of Glaucoma by optic
      nerve head evaluation and perimetric parameters, allows a patient's eye to be
      categorized as having - mild, moderate or severe Glaucomatous damage. An initial
      attempt should be made to achieve the following IOP range for both POAG or PACG
      after an iridotomy. In mild glaucoma the initial target IOP range could be kept
      as 15-17 mmHg, for moderate glaucoma 12-15 mmHg and in the severe stage of
      glaucomatous damage 10-12 mmHg. Factoring in baseline IOP, age, vascular
      perfusion parameters, and change on perimetry or imaging during follow up, this
      range may be reassessed over 6 months to a year. "Target" IOP requires further
      lowering when the patient continues to progress or develops a systemic disease
      such as a TIA. Conversely, in the event of a very elderly or sick patient with
      stable nerve and visual field over time, the target IOP could be raised and
      medications reduced. An appropriate use of medications/laser/surgery to achieve
      such a "Target" IOP range in POAG or PACG can maintain visual fields and quality
      of life, preventing Glaucoma blindness.

PMID- 29582810
TI  - Evaluation of macular ganglion cell analysis compared to retinal nerve fiber
      layer thickness for preperimetric glaucoma diagnosis.
AB  - Purpose: To compare the diagnostic ability of the ganglion cell analysis (GCA)
      and retinal nerve fiber layer (RNFL) protocol on optical coherence tomography
      (OCT), to diagnose preperimetric glaucoma. Methods: A prospective, cross
      sectional study of 275 adult patients including 47 early glaucoma (mean deviation
      better than -6.0 D), 150 glaucoma suspects (106 with suspicious discs and 44
      ocular hypertensive (OHT), and 78 normal controls was done. Eligible participants
      were scanned with the spectral domain CirrusTM OCT (Carl Zeiss Meditec, Dublin,
      CA). Average peripapillary RNFL thickness and GCA measurements were obtained.
      Area under receiver operating characteristic (AROC) curves were used to evaluate
      discriminant value of both protocols to diagnose likely preperimetric glaucoma
      among glaucoma suspects. Results: Average RNFL and GCA were significantly thinner
      in glaucoma patients compared to glaucoma suspects and normal controls (P <
      0.001). The RNFL was 92.26 +/- 8.8 MU in normal controls, 87.9 +/- 12.12 MU in
      glaucoma suspects and significantly thinner in POAG (70.29 +/- 10.18 MU; P <
      0.001). The GCA was 81.94 +/- 6.17 MU in normal controls, 77.69 +/- 9.03 MU in
      glaucoma suspects, and significantly thinner in POAG (69.36 +/- 11.06 MU; P <
      0.001). AROCs for discriminating glaucoma suspects from normal were modest, with
      no difference in AROC of average RNFL or GCA measurements (DeLong; P = 0.93).
      Average RNFL thickness had significantly greater AROC values than average GCA for
      discriminating glaucoma suspects (both suspicious discs and OHT) from glaucoma (P
      = 0.03 and 0.05, respectively. AROC for diagnosing glaucoma was significantly
      better (P = 0.02) for RNFL (0.88 +/- 0.03) than GCA (0.77 +/- 0.04). Conclusion:
      In the present time, GCA measurements, as provided by the SD-OCT, do not appear
      to outperform RNFL measurements in the diagnosis of preperimetric glaucoma.

PMID- 29582811
TI  - Application of high intensity focused ultrasound for treatment of open-angle
      glaucoma in Indian patients.
AB  - Purpose: The aim of this study is to assess the efficacy of ultrasound
      cycloplasty (UCP) in Indian patients with open angle glaucoma (OAG). Methods: A
      prospective interventional study was designed to treat 73 eyes of 73 patients
      with OAG with the EyeOP1 device equipped with six miniaturized cylindrical
      piezoelectric transducers. Two treatment protocols of ultrasound delivery
      depending on exposure time (8 s and 10 s of shot per transducer) were used.
      Complete ophthalmic examination, ocular biometry and anterior segment optical
      coherence tomography were performed preoperatively and patients were followed up
      at day 1, day 7 and months 1, 2, 3, 6, and 12. The primary outcome measure was
      "successful" intraocular pressure (IOP) control defined as IOP reduction >=20%
      from baseline and IOP value >5 mm Hg at the last follow-up visit. Secondary
      outcomes were the occurrence of complications and mean IOP during the follow-up
      period. Results: In all patients, the mean IOP reduced from 23.5 +/- 3.0 mmHg
      before treatment to 15.7 +/- 5.4 mmHg at 12 months (P < 0.05). Successful IOP
      control after a single procedure was 78.3% (79% and 78% in the 8 s and 10 s
      groups, respectively) at 12 months. Overall, the mean IOP reduction achieved in
      responding patients was 41% (standard deviation = 12%). Notwithstanding minor
      side effects such as transient pain, anterior chamber reaction, and refractive
      error changes, no major intraoperative or postoperative complications (severe
      hypotony or phthisis) were observed during the follow-up. Conclusion: Our short
      term results reveal that UCP is a simple, safe, and noninvasive procedure which
      enables to significantly reduce the IOP in patients with OAG. The study results
      in Indian eyes corroborate findings in earlier studies on Caucasian eyes.

PMID- 29582812
TI  - Changing uveitis patterns in South India - Comparison between two decades.
AB  - Purpose: Changing pattern of uveitis in a subset of a population is an important
      ocular health indicator. Methods: A comparative study was done between uveitis
      patients of 2013 and 1995 using two proportions Z-test. Results: In 2013, 352 new
      uveitis cases were examined. Males 56%, females 44%; unilateral 30.4%; bilateral
      in 69.6%. A specific diagnosis achieved in 66.2%. Anterior uveitis was seen in
      35.22%, intermediate uveitis in 30.11%, posterior uveitis in 25%, and panuveitis
      in 9.65%. There was no significant difference in the incidence of new uveitic
      cases (1.04% vs. 1.8%). A decline in male preponderance from 64% to 56% (P =
      0.0187) was observed. In both studies, anterior uveitis was the most common but
      human leukocyte antigen-B27 positivity uveitis had increased (29.83% vs. 14.5%; P
      < 0.05). Intermediate uveitis was the second-most common type instead of
      posterior uveitis (P = 0.0006). In posterior uveitis cases, etiology was
      established in 88.6% versus 56.06% cases (P < 0.05). The most common cause of
      posterior uveitis was tuberculosis (TB) (35.2%). Viral retinitis had increased to
      6.81% from 0.76% (P < 0.05). However, a declining trend in cases of toxoplasmosis
      was observed (P = 0.0545). The cause of panuveitis was comparable in both
      studies. The prevalence of TB has significantly increased in the present era
      (22.5% vs. 0.64%; P < 0.0001) and was the proven etiological cause of uveitis in
      overall 22.5% of which 4.8% cases were of anterior uveitis cases, 7.1% cases of
      intermediate uveitis cases, 8.8% cases of posterior uveitis cases, and 1.8% of
      panuveitis cases. Conclusion: A shifting paradigm of uveitis over the past two
      decades was observed.

PMID- 29582813
TI  - Changing patterns in uveitis South India: Comparison between two decades.

PMID- 29582814
TI  - Change in choroidal vascularity in acute central serous chorioretinopathy.
AB  - Purpose: This study aims to compare the effect of laser photocoagulation or
      observation on choroidal vascularity in acute central serous chorioretinopathy
      (CSCR). Methods: A retrospective analysis of 30 patients with acute CSCR treated
      either with laser photocoagulation (16 eyes) or sham laser (14 eyes) was
      performed. Demographic details, visual acuity (VA) assessment, and other relevant
      clinical data were considered from baseline to the 3rd and 6th month follow-up
      visits. Participants with chronic CSCR and missing follow-up or inadequate data
      were excluded. Choroidal analysis including choroidal thickness and choroidal
      vascularity index (CVI) assessment was done for each visit using Spectral Domain
      (SD) Optical Coherence Tomography (OCT) images. Results: In laser arm group,
      there was a statistically significant change in VA, contrast sensitivity and
      central macular thickness (CMT) and neurosensory detachment (NSD) (P < 0.05) at
      the 3rd and 6th month visits. However, there was no statistically significant
      difference in subfoveal choroidal thickens (SFCT) and CVI (P > 0.05) at both the
      visits. In sham laser group, similarly, there was a significant improvement in
      VA, contrast sensitivity, CMT, and CVI (P < 0.05) at the 3rd and 6th month
      visits. There was significant reduction in NSD at the 3rd month; however, it was
      not statistically significant at the 6th month visit. SFCT did not change
      significantly at both the visits. There was no significant difference for the
      changes in parameters between the groups at the 6th month. Regression analysis
      showed no significant correlation with final VA with any of the baseline
      parameters. Conclusion: Early laser photocoagulation does lead to change in
      choroidal morphology, though insignificant, in comparison to observation. The
      present data, yet again, support no additional benefit of early laser
      photocoagulation in acute CSCR.

PMID- 29582815
TI  - Biochemical scenario behind initiation of diabetic retinopathy in type 2 diabetes
      mellitus.
AB  - Purpose: Despite the disease having similar glycemic status and duration
      microangiopathy in some patients develop within few years whereas it doesn't
      appear as a health complication in some diabetics for a considerable period. This
      study is undertaken to assess the hyperglycemia-induced biochemical background
      behind the development of diabetic retinopathy (DR) in type 2 diabetes mellitus
      (DM). Methods: Following proper diagnosis, 100 patients of type 2 DM of 10-12
      years duration having no DR, and 42 patients of type 2 DM of the same duration
      and glycemic status as the second group, with mild retinopathy were recruited in
      the study. Lactic acid, glutamate, malondialdehyde (MDA), nitrate, advanced
      glycation end-products (AGEs), peripheral blood mononuclear cell reactive oxygen
      species (ROS), vascular endothelial growth factor (VEGF), and its receptor 2
      (VEGFR2) in these two groups were produced in an assay following standard
      methodology. Results: Biochemical markers of anaerobic glycolysis, lipid
      peroxidation, AGEs, glutamate concentration, oxidative stress, and expression of
      VEGF and its VEGFR2 with significantly elevated markings were found in them who
      developed earliest stage of DR rather than them who had not. Conclusion:
      Hyperglycemia-induced anomalous glucose metabolism, lipid peroxidation, advanced
      glycation, glutamate toxicity, and oxidative stress create a background where
      apoptosis of retinal capillary endothelial cells invite increased expression of
      VEGF and VEGFR2, these being the crucial factors behind the development of
      diabetic microangiopathy.

PMID- 29582816
TI  - Prevalence, progression, and outcomes of diabetic retinopathy during pregnancy in
      Indian scenario.
AB  - Purpose: The objective of this study is to evaluate pattern of diabetic
      retinopathy (DR) during pregnancy in females with pregestational diabetes
      mellitus (DM). Methods: This is an ambispective observational cohort study
      conducted at an Indian tertiary care centre. A total of 50 pregnant females with
      pregestational DM were included while those with gestational DM were excluded
      from the study. Ocular examination (inclusive of fundus photography) was
      conducted and systemic parameters (inclusive of Glycated hemoglobin) were
      assessed during each of the 3 trimesters and 3 months postpartum. The prevalence
      and progression of DR during pregnancy in the study cohort were the main outcome
      measures. Results: Three of the 50 patients had type 1 DM while 47 had type II
      DM. All the patients with type I DM were insulin dependent while 19 patients with
      type II DM were insulin dependent. Overall prevalence of DR was 8% (4/50); 2
      cases had nonproliferative DR (NPDR), and 2 had proliferative DR (PDR). During
      the study period, worsening was seen in both the patients with PDR and one
      required vitrectomy. Mean visual acuity in patients with PDR decreased from 0.77
      logMAR units at presentation to 1.23 logMAR at final follow-up. There was no
      change in the mean visual acuity of patients with NPDR. None of the patients with
      NPDR converted to PDR. There was no new onset DR in the patients without DR at
      presentation. Assessment of risk factors for DR revealed significantly higher
      duration of DM (14 +/- 6.32 years vs. 3.43 +/- 1.43 years, P = 0.0008). The
      median age was also higher in the DR patients (31 years vs. 29 years, P = 0.32).
      Conclusion: No new onset cases were seen during the course of pregnancy and no
      conversion from NPDR to PDR was seen; however, a worsening of the two PDR cases
      was observed. No cases of DR were seen in noninsulin-dependent DM. None of the
      four participants with DR showed a spontaneous resolution of DR postpartum.
      Patients with PDR and long-standing DM require careful observation during
      pregnancy. A registry of diabetic mothers should be set up for development of
      guidelines for managing such cases.

PMID- 29582817
TI  - Diabetic retinopathy in patients with diabetic foot syndrome in South India.
AB  - Purpose: The purpose was to study the retinopathy status in diabetic patients
      with a risk of diabetic foot (DF) syndrome visiting a tertiary care hospital in
      South India. Methods: In this cross sectional study all patients with diabetes
      mellitus (DM) with a risk of DF syndrome, visiting a tertiary care hospital
      during the study period, underwent an ophthalmological evaluation for
      documentation of their retinopathy status. Results: One hundred and eighty-two
      patients diagnosed to have a risk profile for DF syndrome were included in the
      study. Their mean age was 59.28 years and 75.27% were males. The mean duration of
      Type 1 and Type 2 variants of DM was 14.9 years and 10.9 years, respectively. Of
      the 182 patients, 67.58% had retinopathy changes. Proliferative diabetic
      retinopathy (DR) constituted 17.88% of the total patients with retinopathy. An
      increased presence of retinopathy in patients with an increased risk grade of DF
      was found significant by the Chi-square test (P < 0.001). Conclusion: Our study
      found an increased presence of DR in a South Indian cohort with DF syndrome. The
      severity of retinopathy was greater in patients with higher grades of risk for
      DF. The establishment of an association between DR and DF syndrome will help in
      developing an integrated management strategy for these two debilitating
      consequences of diabetes.

PMID- 29582818
TI  - Association of exudative age-related macular degeneration with matrix
      metalloproteinases-2 (-1306 C/T) rs243865 gene polymorphism.
AB  - Purpose: Age-related macular degeneration (AMD) is a disease of the macula that
      significantly affects eyesight and leads to irreversible central vision loss.
      Recent studies have demonstrated that angiogenesis is the most important
      mechanism of AMD development. It is associated with extracellular remodeling
      involving different proteolytic systems, among them matrix metalloproteinases
      (MMPs), which play an essential role in the etiopathogenesis of AMD. The main
      objective of the present study was to determine the relationship between
      exudative AMD and MMP-2 (-1306 C/T) rs243865 polymorphism. Methods: The study
      enrolled 267 patients with exudative AMD and 318 controls. DNA was extracted from
      peripheral venous blood leukocytes by commercial kits. Genotyping of MMP-2 (-1306
      C/T) rs243865 was carried out using real-time polymerase chain reaction method.
      Results: The analysis of MMP-2 (-1306 C/T) polymorphism did not reveal any
      differences in the distribution of CC, CT, and TT genotypes between the exudative
      AMD and control groups: 58.8%, 31.5% and 9.7% vs. 59.75%, 33.96% and 6.29%,
      respectively, P = 0.287). When the study population was subdivided into age
      groups, MMP-2 (-1306 C/T) rs243865 CT genotype showed 5.7-fold increased the risk
      of exudative AMD development compared to CC and TT genotypes together in younger
      (<65 years) males group (P = 0.05). Conclusion: MMP-2 (-1306 C/T) polymorphism is
      associated with exudative AMD development in younger males.

PMID- 29582819
TI  - Vitreous rebleed following sutureless vitrectomy: Incidence and risk factors.
AB  - Purpose: This study aims to evaluate the incidence and risk factors for vitreous
      rebleed (VRB) following 25-gauge sutureless vitrectomy for vitreous hemorrhage
      (VH) in diabetic retinopathy. Methods: A retrospective review of 190 diabetic
      patients having undergone vitrectomy for VH at a tertiary eye care center was
      analyzed. Demographic data of patients along with risk factors such as blood
      sugar levels (BSL), blood pressure (BP), anticoagulant use, and pan-retinal
      photocoagulation status (PRP) were tabulated. Depending on the commencement of
      VRB, patients were divided into immediate rebleed-within 2 weeks and delayed
      rebleed-beyond 2-4 weeks. Results: Forty-one patients had VRB, out of which 18
      patients had immediate VRB and 23 patients had delayed VRB. The average duration
      between vitrectomy and VRB was 3.28 months. Twenty-eight patients were male and
      13 were females. Average age at presentation was 53.8 years. Thirty-four patients
      (82.9%) were found to have high BSL and 28 patients (68.3%) had high BP and they
      developed rebleed (P < 0.01) after an initial hemorrhage-free period (average =
      5.15 months). Fifteen patients (36.6%) underwent first time PRP intraoperatively,
      and they had immediate rebleed (P < 0.01) without any hemorrhage-free period
      (average = 0.9 months). Eight patients (19.5%) were on perioperative
      anticoagulants; however, their statistical significance did not persist in the
      multivariable model. There were neither age nor gender predilection toward
      rebleed (P > 0.05). Conclusion: The incidence rate of VRB was found to be 21.6%.
      Age and gender did not contribute to rebleed. Intraoperative PRP was a risk
      factor for immediate rebleed. Poor glycemic and BP control was a risk factor for
      delayed rebleed.

PMID- 29582821
TI  - Pars-plana fluid aspiration for positive vitreous cavity pressure in anterior
      segment surgeries.
AB  - Positive vitreous pressure due to misdirection of aqueous or choroidal effusion
      leads to shallowing of the anterior chamber (AC) before or during anterior
      segment surgeries. This shallow AC if not addressed makes surgery difficult and
      increases the risk of surgical complications. Methods to prevent and manage this
      condition described in literature are not without problems. We describe a
      minimally invasive technique of passing a 30G needle through the pars-plana to
      aspirate misdirected fluid from vitreous cavity either as a prophylaxis just
      before surgery or during it, thereby decreasing positive vitreous pressure. This
      technique, used in 12 eyes, seems to be effective in patients with angle-closure
      glaucoma, malignant glaucoma, and per-operative sudden increase in vitreous
      pressure during surgery. Small-incision surgeries are ideally suited for this
      procedure. This minimally invasive technique is simple to perform and
      complications are unlikely to be more than what is seen with intravitreal
      injections.

PMID- 29582820
TI  - Surgical technique for management of isolated lenticular coloboma with high
      corneal astigmatism.
AB  - We describe a surgical technique for the correction of isolated congenital
      lenticular coloboma associated with high corneal astigmatism. Transscleral
      fixation of the capsular bag with a single eyelet Cionni capsular tension ring
      was followed by in-the-bag implantation of a toric intraocular lens (IOL). This
      lead to complete correction of the lenticular defect and perfect alignment of the
      toric lens. In this case, the child attained an unaided distance visual acuity of
      20/30 following amblyopia therapy and a well-aligned toric IOL at 12 months of
      follow-up. This technique can be used in cases with concomitant lenticular
      coloboma and significant corneal astigmatism.

PMID- 29582822
TI  - Floating venous loop in regressed retinopathy of prematurity.

PMID- 29582823
TI  - Bilateral multifocal retinal pigment epithelium detachment and
      pachychoroidopathy.

PMID- 29582824
TI  - Rapid regression of retinal neovascularization following intravitreal bevacizumab
      in branch retinal vein occlusion imaged by optical coherence tomography
      angiography.

PMID- 29582825
TI  - Mud-splattered fundus.

PMID- 29582826
TI  - Actinomycetes canaliculitis complicating congenital nasolacrimal duct obstruction
      in an infant.
AB  - Actinomyces israelii is a Gram-positive anaerobic organism commonly associated
      with canaliculitis in adults. Pediatric canaliculitis is relatively rare,
      especially in infancy. We report the case of an 11-month-old boy who presented
      with co-existing canaliculitis and congenital nasolacrimal obstruction. The
      presenting signs included epiphora, discharge, conjunctival congestion, and
      matting of lashes. On examination, punctual pouting, regurgitation, and yellow
      canaliculiths were noted. A punctoplasty and canalicular curettage were performed
      along with nasolacrimal probing. Microbiological tests confirmed the organisms to
      be A. israelii. We discuss the clinical features and management of Actinomyces
      associated canaliculitis and review the available literature on pediatric
      canaliculitis.

PMID- 29582827
TI  - Successful treatment of allergic conjunctival granuloma by topical tacrolimus: A
      clinicopathologic case report.
AB  - Allergic conjunctival granuloma is a rare cause of conjunctival ocular lesions.
      The aim of this case report was to present a successful treatment of an allergic
      conjunctival granuloma with topical tacrolimus eye drops. A 20-year-old female
      presented with bilateral multiple yellow nodules of the bulbar conjunctival
      epithelium and conjunctival injection. The patient had tearing, photophobia,
      itching, foreign body sensation, and red eye. The patient's signs and symptoms
      progressed despite the use of topical steroids. The patient was treated by
      application of tacrolimus eye drop (0.005%) in her right eye every 6 h while the
      left eye was put on placebo. Her signs and symptoms were recorded at each visit.
      After 3 weeks' therapy with topical tacrolimus eye drop, the patient became
      asymptomatic in her right eye and conjunctival granulomas fully resolved. Topical
      tacrolimus seems to be an effective therapeutic option for the treatment of
      allergic conjunctival granulomas.

PMID- 29582828
TI  - Optical coherence tomography angiography features of choroidal hemangioma.
AB  - This is an observational case series of four cases of choroidal hemangioma. All
      cases underwent OCT angiography with swept source OCTA (Topcon DRI OCT Triton
      plus) 6 mm * 6 mm protocol. OCTA at the level of large choroidal vessels
      demonstrated peculiar vascular pattern in all four eyes. Patterns observed were
      bag of worms, spaghetti like and vessels with terminal bulbs. In eye with diffuse
      choroidal hemangioma comparison of choroidal vascular pattern with the
      contralateral eyes showed significant difference in the vascular architecture.
      OCTA is an excellent non invasive tool in assessing the choroidal vascular
      pattern in eyes with choroidal hemangioma.

PMID- 29582829
TI  - Choroidal osteoma in a preterm infant.
AB  - Choroidal osteoma (CO) is a rare, benign, and usually unilateral intraocular
      tumor composed of mature bone affecting the choroid. It appears as slightly
      elevated, yellowish-white, or orange choroidal mass with well-defined borders. It
      is commonly encountered in young female adults. Here, we report findings of a 4
      week-old premature baby with CO in her left eye which was detected during a
      routine examination for "retinopathy of prematurity." We believe that this case
      is the youngest patient reported with CO which showing that this pathology can be
      encountered even in a newborn.

PMID- 29582830
TI  - Multimodal imaging of choroidal nodules in neurofibromatosis type-1.
AB  - Choroidal nodules in neurofibromatosis type-1 are common and are best imaged with
      near-infrared reflectance (NIR) imaging. The authors describe swept-source
      optical coherence tomography angiography (SSOCTA) of choroidal nodules. These
      nodules are seen as hyperflow areas on SSOCTA and correlate well to bright
      patches on NIR imaging. The utility of multicolor scanning laser imaging in
      detecting these abnormalities is also described.

PMID- 29582831
TI  - A rare case of unilateral diffuse melanocytic proliferation.
AB  - A 67-year-old woman presented with metamorphopsia in the right eye. Leopard
      mottling was seen temporal to the fovea oculus dexter with corresponding hyper-
      and hypo-autofluorescent lesions on fundus autofluorescence. Spectral domain
      optical coherence tomography revealed hyperreflective dots in the retinal pigment
      epithelium and choroid with subretinal fluid (SRF). Intravitreal bevacizumab was
      administered with which SRF resolved, albeit with increase in the areas of
      mottling. The patient was diagnosed to have metastatic ductal carcinoma of the
      right breast. It is important to bear in mind that the well-known entity of
      bilateral diffuse uveal melanocytic proliferation can rarely present
      unilaterally.

PMID- 29582832
TI  - Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.
AB  - We report a case of progressive outer retinal necrosis (PORN) in a patient of
      microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as
      cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster
      virus and she was treated with oral and intravitreal antivirals, along with
      discontinuation of one of the immunosuppressive agents, i.e. rituximab, which
      might have led to reactivation of the virus causing necrotizing retinitis
      lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are
      necessary to manage immunological disorders such as MPA. However, they may
      predispose the patient to serious complications like viral infections, including
      PORN.

PMID- 29582833
TI  - Presumably contaminated intravenous infusion-induced Aspergillus terreus
      endogenous endophthalmitis presenting with posterior hypopyon.
AB  - A 36-year-old immunocompetent man developed endogenous endophthalmitis 1 week
      after intravenous fluid infusion in a rural setting. Large submacular abscess
      with posterior hypopyon warranted urgent vitrectomy which revealed Aspergillus
      terreus on fungal culture. Intravitreal and oral antifungals lead to resolution
      of inflammation with satisfactory anatomic outcome but poor visual outcome due to
      submacular scar.

PMID- 29582834
TI  - Management of multi drug resistant endogenous Klebsiella pneumoniae
      endophthalmitis with intravitreal and systemic colistin.
AB  - We report a case of a 35-year-old male with a pancreatic pseudocyst, who
      developed bilateral endogenous endophthalmitis, 4 days after surgical drainage of
      the pseudocyst. Bacterial cultures of the pancreatic drain fluid and the vitreous
      tap showed the growth of Klebsiella pneumoniae. The cultured organism was
      resistant to all the tested antibiotics except colistin. Intravenous colistin was
      instituted and three injections of intravitreal colistin were given in the left
      eye of the patient. Complete resolution of infection was seen and visual acuity
      of 6/6 was regained in both eyes, which was maintained at 4-month follow-up.

PMID- 29582835
TI  - Commentary: Management of endogenous endophthalmitis: Ophthalmologist in the role
      of a physician.

PMID- 29582836
TI  - Unique case of midbrain tuberculoma presenting as isolated inferior rectus palsy
      with nystagmus.
AB  - Isolated brain stem tuberculoma constitutes about 5% of all intracranial
      tuberculomas. A case of isolated inferior rectus palsy with downbeat nystagmus
      due to presumed midbrain tuberculoma in an immunocompetent patient is described
      here. This report documents a rare entity of a combination of partial third nerve
      palsy with pupil involvement along with downbeat nystagmus.

PMID- 29582837
TI  - Comment on: Antibiotic prophylaxis in cataract surgery - An evidence-based
      approach.

PMID- 29582838
TI  - Comment on: Bilateral idiopathic spontaneous filtering bleb with ectopia lentis:
      A case report and review of literature.

PMID- 29582839
TI  - Comment on: Viscoelastic-augmented trabeculectomy - A newer concept.

PMID- 29582840
TI  - Response to comment on: Bilateral idiopathic spontaneous filtering bleb with
      ectopia lentis: A case report and review of literature.

PMID- 29582841
TI  - Erratum: Age and myopia associated optical coherence tomography of retina and
      choroid in pediatric eyes.
AB  - [This corrects the article DOI: 10.4103/ijo.IJO_652_17].

PMID- 29582842
TI  - Universal health coverage in the World Health Organization South-East Asia
      Region: how can we make it "business unusual"?

PMID- 29582843
TI  - A framework for comparative analysis of health systems: experiences from the Asia
      Pacific Observatory on Health Systems and Policies.
AB  - Drawing on published work from the Asia Pacific Observatory on Health Systems and
      Policies, this paper presents a framework for undertaking comparative studies on
      the health systems of countries. Organized under seven types of research
      approaches, such as national case-studies using a common format, this framework
      is illustrated using studies of low- and middle-income countries published by the
      Asia Pacific Observatory. Such studies are important contributions, since much of
      the health systems research literature comes from high-income countries. No one
      research approach, however, can adequately analyse a health system, let alone
      produce a nuanced comparison of different countries. Multiple comparative studies
      offer a better understanding, as a health system is a complex entity to describe
      and analyse. Appreciation of context and culture is crucial: what works in one
      country may not do so in another. Further, a single research method, such as
      performance indicators, or a study of a particular health system function or
      component, produces only a partial picture. Applying a comparative framework of
      several study approaches helps to inform and explain progress against health
      system targets, to identify differences among countries, and to assess policies
      and programmes. Multi-method comparative research produces policy-relevant
      learning that can assist countries to achieve Sustainable Development Goal 3:
      ensure healthy lives and promoting well-being for all at all ages by 2030.

PMID- 29582844
TI  - Pushing the boundaries of research on human resources for health: fresh
      approaches to understanding health worker motivation.
AB  - A country's health workforce plays a vital role not only in serving the health
      needs of the population but also in supporting economic prosperity. Moreover, a
      well-funded and well-supported health workforce is vital to achieving universal
      health coverage and Sustainable Development Goal 3 to ensure healthy lives and
      promote well-being for all at all ages. This perspective article highlights the
      potential of underutilized health policy and systems research (HPSR) approaches
      for developing more effective human resources for health policy. The example of
      health worker motivation is used to showcase four types of HPSR (exploratory,
      influence, explanatory and emancipatory) that move beyond describing the extent
      of a problem. Most of the current literature aiming to understand determinants
      and dynamics of motivation is descriptive in nature. While this is an important
      basis for all research pursuits, it often gives little information about
      mechanisms to improve motivation and strategies for intervention. Motivation is
      an essential determinant of health worker performance, particularly for those
      working in difficult conditions, such as those facing many health workers in low-
      and middle-income countries. Motivation mediates health workforce performance in
      multiple ways: internally governing health worker behaviour; informing decisions
      on becoming a health worker; workplace location and ability to perform; and
      influencing willingness to engage politically. The four fresh research approaches
      described can help policy-makers better understand why health workers behave the
      way they do, how interventions can improve performance, the mechanisms that lead
      to change, and strategies for empowering health workers to be agents of change
      themselves.

PMID- 29582845
TI  - The burden of iron-deficiency anaemia among women in India: how have iron and
      folic acid interventions fared?
AB  - Iron-deficiency anaemia (IDA) among women in India is a problem of major public
      health significance. Using data from three waves of the National Family Health
      Survey, this article discusses the burden of and trend in IDA among women in
      India, and discusses the level of iron and folic acid (IFA) supplementation and
      its potential role in reducing the burden of IDA. Between 2005-2006 and 2015
      2016, IDA in India decreased by only 3.5 percentage points (from 56.5% in 2005
      2006 to 53.0% in 2015-2016) for women aged 15-49 years. However, during the same
      period, of 27 states compared, IDA increased in eight: Delhi, Haryana, Himachal
      Pradesh, Kerala, Meghalaya, Tamil Nadu, Punjab and Uttar Pradesh; furthermore,
      some of these (e.g. Kerala) are states that rank among the highest on the state
      Human Development Index but had failed to contain the burden of IDA. Although
      there is a standard guideline for IFA supplementation in place, the IFA
      intervention appears to be ineffective in reducing the burden of IDA in India
      (nationally only 30.3 % of mothers consumed IFA for 100 days or more when they
      were pregnant), probably due to irregular consumption of IFA where the provision
      of screening under the National Iron+ Initiative scheme appears to be
      unsuccessful. To strengthen the IFA intervention and its uptake, a concerted
      effort of community-level health workers (accredited social health activists,
      auxiliary nurse midwives and anganwadi workers) is urgently needed. In addition,
      food-based strategies (dietary diversification and food fortification), food
      supplementation and improvement of health services are required to reduce the
      burden of anaemia among women in India.

PMID- 29582846
TI  - Social autopsy: a potential health-promotion tool for preventing maternal
      mortality in low-income countries.
AB  - Despite significant global improvements, maternal mortality in low-income
      countries remains unacceptably high. Increasing attention in recent years has
      focused on how social factors, such as family and peer influences, the community
      context, health services, legal and policy environments, and cultural and social
      values, can shape and influence maternal outcomes. Whereas verbal autopsy is used
      to attribute a clinical cause to a maternal death, the aim of social autopsy is
      to determine the non-clinical contributing factors. A social autopsy of a
      maternal death is a group interaction with the family of the deceased woman and
      her wider local community, where facilitators explore the social causes of the
      death and identify improvements needed. Although still relatively new, the
      process has proved useful to capture data for policy-makers on the social
      determinants of maternal deaths. This article highlights a second aspect of
      social autopsy - its potential role in health promotion. A social autopsy
      facilitates "community self-diagnosis" and identification of modifiable social
      and cultural factors that are attributable to the death. Social autopsy therefore
      has the potential not only for increasing awareness among community members, but
      also for promoting behavioural change at the individual and community level.
      There has been little formal assessment of social autopsy as a tool for health
      promotion. Rigorous research is now needed to assess the effectiveness and cost
      effectiveness of social autopsy as a preventive community-based intervention,
      especially with respect to effects on social determinants. There is also a need
      to document how communities can take ownership of such activities and achieve a
      sustainable impact on preventable maternal deaths.

PMID- 29582847
TI  - Current status of master of public health programmes in India: a scoping review.
AB  - There is a recognized need to improve training in public health in India.
      Currently, several Indian institutions and universities offer the Master of
      Public Health (MPH) programme. However, in the absence of any formal body or
      council for regulating public health education in the country, there is limited
      information available on these programmes. This scoping review was therefore
      undertaken to review the current status of MPH programmes in India. Information
      on MPH programmes was obtained using a two-step process. First, a list of all
      institutions offering MPH programmes in India was compiled by use of an internet
      and literature search. Second, detailed information on each programme was
      collected via an internet and literature search and through direct contact with
      the institutions and recognized experts in public health education. Between 1997
      and 2016-2017, the number of institutions offering MPH programmes increased from
      2 to 44. The eligibility criteria for the MPH programmes are variable. All
      programmes include some field experience. The ratio of faculty number to students
      enrolled ranged from 1:0.1 to 1:42. In the 2016-2017 academic year, 1190 places
      were being offered on MPH programmes but only 704 students were enrolled. MPH
      programmes being offered in India have witnessed a rapid expansion in the past
      two decades. This growth in supply of public health graduates is not yet matched
      by an increased demand. Despite the recognized need to strengthen the public
      health workforce in India, there is no clearly defined career pathway for MPH
      graduates in the national public health infrastructure. Institutions and public
      health bodies must collaborate to design and deliver MPH programmes to overcome
      the shortage of public health professionals, such that the development goals for
      India might be met.

PMID- 29582848
TI  - Factors associated with delivery at home in Bhutan: findings from the National
      Health Survey 2012.
AB  - Background: Despite Bhutan's remarkable progress in the area of maternal and
      child health during the era of the Millennium Development Goals, a large
      proportion of pregnant women are still delivering at home with no skilled
      attendant. Limited empirical studies have been carried out to understand the
      factors associated with delivery at home in Bhutan. Methods: This cross-sectional
      analytical study used secondary data collected in the nationally representative
      National Health Survey 2012. The survey included a total of 2213 women aged 15-49
      years who had a live birth in the 2 years preceding the survey and were selected
      using multistage stratified cluster sampling. Weighted analysis was done to
      evaluate determinants for the place of delivery. Unadjusted and adjusted
      prevalence ratios with 95% confidence intervals (CIs) were calculated to assess
      the possible association of factors with home delivery. Results: Out of 2213
      women aged 15-49 years who had a live birth in the 2 years preceding the survey,
      73.7% had an institutional delivery. Coverage of institutional delivery ranged
      from 49.4% in Zhemgang district to 96.1% in Paro district. Women in the poorest
      wealth quintile were 7.35 times more likely to have a birth at home compared to
      women in the richest quintile (adjusted prevalence ratio [aPR]: 7.35, 95% CI:
      2.59-20.9). The older mothers aged 30-49 years were 0.79 times (aPR: 0.79, 95%
      CI: 0.70-0.88) less likely to have a home delivery than mothers aged 15-19 years.
      Women who had fewer than four antenatal care visits were 1.50 times (aPR: 1.50,
      95% CI: 1.35-1.66) more likely to give birth at home compared to those who had
      four or more visits. The mothers giving birth for a third or more time were 1.88
      times (aPR: 1.88, 95% CI: 1.60-2.22) more likely to give birth at home compared
      to those giving birth for the first time. Women living in rural areas were 2.87
      times (aPR: 2.87, 95% CI: 1.42-5.77) more likely to deliver at home compared to
      those living in urban areas and women living in the eastern region of the country
      were 1.35 times (aPR: 1.35, 95% CI: 1.17-1.55) more likely to have a home
      delivery compared to those living in the western region. Conclusion: Lower
      socioeconomic status, rural location, eastern location, non- first birth, and
      having fewer than four antenatal visits were significant factors associated with
      home delivery. These findings should inform further research and policy to build
      on Bhutan's progress in promoting institutional delivery as the key strategy
      towards improving maternal and child health and achieving the relevant targets of
      Sustainable Development Goal 3.

PMID- 29582849
TI  - Changes in neonatal mortality and newborn health-care practices: descriptive data
      from the Bangladesh Demographic and Health Surveys 2011 and 2014.
AB  - Background: Bangladesh has made major improvements in health outcomes over the
      past two decades, with falls in mortality rates in mothers and in infants and
      young children aged under 5 years. Despite these improvements, neonatal mortality
      rates (NMRs) are high in Bangladesh. This paper describes recent changes in NMRs
      and health-care practices, disaggregated by demographic and socioeconomic
      characteristics. Methods: Summary statistics from the reports of the Bangladesh
      Demographic and Health Survey (BDHS) were examined. The BDHS is a nationally
      representative cross-sectional survey and the two most recent rounds of surveys,
      2007-2011 and 2010-2014, were included in the analysis. The variables considered
      in this study were neonatal deaths and related health-care practices, including
      antenatal care visits, facility-based delivery, assistance from a medically
      trained provider during delivery, postnatal care from a trained provider and
      essential newborn care. Results: Between the two survey periods, NMRs increased
      in Chittagong (average increase 4.5% per year) and Khulna (8.3% per year),
      remained unchanged in Rangpur, and decreased in Barisal (average decrease 19.8%
      per year), Dhaka (12.2% per year), Rajshahi (7.7% per year) and Sylhet (4.8% per
      year). A larger average annual reduction in the NMR was observed in urban areas
      than in rural areas (14.0% versus 2.1%). There was also a large average annual
      reduction in NMR in the fourth and fifth richest quintiles for socioeconomic
      status (SES quintiles; 12.0% and 16.5% per year, respectively). Differences
      according to neonatal sex were also noted: the NMR for female neonates remained
      unchanged and that for male neonates reduced by an annual average of 7.7%.
      General improvements were observed in all health-care practices across all
      demographic and socioeconomic groups. However, the urban-rural gap in the uptake
      of antenatal care services, facility-based delivery, assistance from a medically
      trained provider during delivery, and postnatal care from a trained provider was
      roughly similar in both surveys. A similar unchanging gap was also seen between
      the poorest and richest SES quintiles. Conclusion: The study analysis indicates
      that improvements in NMRs between the two survey periods are mixed. Further
      attention is required to improve the rate of reduction of neonatal mortality in
      some divisions in Bangladesh, and it may be useful to investigate whether the
      higher NMR in rural areas and for households with lower socioeconomic status can
      be reduced by strengthening the uptake of antenatal care services, facility-based
      delivery, assistance from a medically trained provider during delivery, and
      postnatal care from a trained provider. The static NMR for female neonates may
      encourage policy-makers to focus not only on ensuring standard essential newborn
      care practices for both sexes but also on ensuring adequate and appropriate care
      seeking for illness in female neonates.

PMID- 29582850
TI  - Large-scale mHealth professional support for health workers in rural Maharashtra,
      India.
AB  - Expanding mobile telephony in India has prompted interest in the potential of
      mobile-telephone health (mHealth) in linking health workers in rural areas with
      specialist medical advice and other professional services. In 2012, a toll-free
      helpline offering specialist medical advice to community-based health workers
      throughout Maharashtra was launched. Calls are handled via a 24 h centre in Pune,
      staffed by health advisory officers and medical specialists. Health advisory
      officers handle general queries, which include medical advice via validated
      algorithms; blood on-call services; grievance issues; and mental health support -
      the latter calls are transferred to a qualified counsellor. Calls requiring more
      specialist advice are transferred to the appropriate medical specialist. This
      paper describes the experience of the first 4 years of this helpline, in terms of
      the services used, callers, nature of calls, types of queries serviced and
      lessons learnt. In the first 4 years of the helpline, 669 265 calls were
      serviced. Of these calls, 453 373 (67.74%) needed medical advice and were handled
      by health advisory officers. Specialist services were required to address 199 226
      (29.77%) calls. Blood-bank-related services accounted for 7919 (1.18%) calls,
      while 2462 (0.37%) were grievance calls. Counselling for mental health issues
      accounted for 6285 (0.94%) calls. The large-scale mHealth professional support
      provided by this helpline in Maharashtra has reached many health workers serving
      rural communities. Future work is required to explore ways to expand the reach of
      the helpline further and to measure its effectiveness in improving health
      outcomes.

PMID- 29582851
TI  - gammadelta T Cells in Peripheral Blood of Glioma Patients.
AB  - BACKGROUND Glioma is a common brain malignancy, but the effects of the gammadelta
      T cells and their subsets in peripheral blood in patients with glioma have not
      been reported. MATERIAL AND METHODS Flow cytometry was used to analyze the
      functions and expressions of delta T cells and their subsets in peripheral blood
      in healthy controls and patients with glioma. The Vdelta2 T cells and the
      activation of killing function-related signaling pathway were analyzed by Western
      blot assay; the immunosuppressive functions of Vdelta1 T cells were detected by
      CFSE proliferation assay; and the Vdelta2 T cell killing functions were detected
      by killing assay. RESULTS Compared with the healthy controls, the ratio of
      Vdelta1 T cells was significantly increased and the ratio of Vdelta2 T cells was
      significantly decreased. After in vitro culture and anti-TCR gd antibody
      stimulation and in the presence of IL-2, in the patients with glioma, the Vdelta1
      T cells dominated and Vdelta2 T cells were scarce. Flow cytometry staining showed
      that expression of immunosuppression-related molecules on the Vdelta1 T cell
      surface was significantly increased, while the expression of killing function
      related molecules and the activation of killing function-related signaling
      pathway in the Vdelta2 T cells were significantly decreased. Functional test
      results showed that the immunosuppressive function of Vdelta1T cells was enhanced
      and the killing function of Vdelta1T cells was reduced. CONCLUSIONS The ratio and
      function changes of Vdelta1 T cells and Vdelta2 T cells are possibly associated
      with the pathogenesis of glioma.

PMID- 29582852
TI  - The current role of MRI in differentiating multiple sclerosis from its imaging
      mimics.
AB  - This corrects the article DOI: 10.1038/nrneurol.2018.14.

PMID- 29582853
TI  - [Analysis of the effectiveness of assisted reproduction techniques].
AB  - There are a high number of people affected by infertility who require assisted
      reproduction techniques. For this reason the aim of this review was to analyze
      the effectiveness of the interventions carried out using these techniques. A
      systematic peer review was performed on twelve databases. Inclusion criteria
      were: randomized clinical trials, published between 2011 and 2016, and with a
      score greater than two on the Jadad scale. The pharmacological interventions that
      proved effective were the administration of hormones, intrauterine human
      chorionic gonadotropin, gonadotrophin and dehydroepiandrosterone, and metformin.
      An effective surgical intervention, endometrial scratching, was identified. No
      effective non-pharmacological interventions were found. Assisted reproduction
      techniques show heterogeneity in both the interventions included and
      effectiveness criteria (pregnancy rate, live birth rate or implantation rate),
      which makes a unification of criteria necessary.

PMID- 29582854
TI  - [Anticoagulation for continuous renal replacement therapy in critically ill
      patients].

PMID- 29582855
TI  - [How to advance in meeting the challenge of early diagnosis of HIV infection].

PMID- 29582856
TI  - [Evaluation and improvement of healthcare quality in patients with headache
      attending physical therapy].
AB  - BACKGROUND: To evaluate the effects on healthcare quality following
      implementation of a program to improve care for individuals with headache in two
      physical therapy clinics and its association with outcomes and self-perceived
      improvement. METHODS: We assessed healthcare quality by creating a questionnaire
      on fulfilment of fifteen quality criteria included in the clinical history of
      individuals suffering from tension-type, cervicogenic or migraine headaches
      seeking physical therapy between 2010 and 2014. In 2015, after applying a program
      to improve care in one center (C1), we reassessed the same fulfilment
      questionnaire in both centers, using the other center (C2) as control. RESULTS:
      In the first evaluation there was a huge number of cases of non-compliance of all
      the criteria in both centers. After implementation of the care improvement
      program in C1 a significant improvement was observed in some items, as use of a
      headache diary, which rose from 0 to 100%, or use of the HIT-6 disability
      questionnaire, which rose from 30 to 100%. In addition, there was a significant
      improvement in self-perceived health status after implementation of the care
      program in C1. CONCLUSIONS: The implementation of a care improvement program was
      effective in improving healthcare quality for individuals with headache attending
      physical therapy services.

PMID- 29582857
TI  - Gastric ischemia due to critical stenosis of the celiac trunk.
AB  - Gastric ischemia (GI) results from diffuse or localized vascular insufficiency
      caused by different aetiologies such as systemic hypotension, vasculitis,
      disseminated thromboembolism and celiac or mesenteric stenosis. We present a case
      of gastric ischemia due to critical stenosis of the celiac artery treated using
      endovascular therapy. The celiac artery is the first major branch of the
      abdominal aorta and provides some of the blood supply to the stomach through the
      left gastric artery and other organs like the spleen (splenic artery branch) and
      the liver. Although the collateral blood supply to the stomach is protective,
      systemic hypotension or occlusion of the main arteries, as in the case of our
      patient, may result in gastric ischemia. The stent placement is an alternative to
      surgery in patients with high comorbidity and with good outcomes. The clinical
      awareness of this syndrome will allow gastroenterologists and radiologists to
      appropriately diagnose and manage affected patients.

PMID- 29582858
TI  - [End of life care: deliberating on facts and values].

PMID- 29582859
TI  - [Need for a holistic and quantitative approach for diagnosing].

PMID- 29582860
TI  - Covariate determinants of effective dosing regimens for time-dependent beta
      lactam antibiotics for critically ill patients.
AB  - AIMS: Critically ill patients undergoing aggressive fluid resuscitation and
      treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are
      at risk for sub-therapeutic plasma concentrations. The aim of this study was to
      assess the impact of two covariates - creatinine clearance (Clcr) and cumulative
      fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target
      attainment within a week of treatment with meropenem (ME) or
      piperacillin/tazobactam (PIP/TZB). METHODS: In this prospective observational
      pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical
      Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free
      antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC)
      to obtain maximum bactericidal activity. Drug concentration was measured using
      liquid chromatography-tandem mass spectrometry. RESULTS: The treatment of both 8
      septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized
      patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18
      patients (44%) manifested augmented renal clearence (ARC) where Clcr >=130
      mL/min/1.73 m2. Maximum changes were reported on days 2-3: the median positive
      CFB followed by the large median volume of distribution: Vdme=70.3 L (41.9
      101.5), Vdpip = 46.8 L (39.7-60.0). 100%fTme>MIC was achieved in all patients on
      ME (aged >=60 years), and only in two patients (non-ARC, aged >=65 years) out of
      10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFBpip
      with Vdpip (P=0.021). CONCLUSION: Assuming that the positive correlation between
      CFB and Vd exists for piperacillin in the setting of the pathological state, then
      CFB should predict Vdpip across subjects at each and every time point.

PMID- 29582861
TI  - Erratum: Author Correction: Cellular and molecular synergy in AS01-adjuvanted
      vaccines results in an early IFNgamma response promoting vaccine immunogenicity.
AB  - [This corrects the article DOI: 10.1038/s41541-017-0027-3.].

PMID- 29582868
TI  - Room temperature synthesis of pH-switchable polyaniline quantum dots as a turn-on
      fluorescent probe for acidic biotarget labeling.
AB  - The synthesis of well-defined light-element-derived quantum dots (LEQDs) with
      advanced optical properties under mild conditions is highly desirable yet
      challenging. Here, a polyaniline (PANI) structure is introduced into carbon-rich
      LEQDs to yield well-defined, fluorescent polyaniline quantum dots (PAQDs),
      PAQD24, through a one-pot room temperature reaction. The mild synthetic
      conditions effectively minimize the defects introduced during the conventional
      synthesis and endow PAQD24 with desirable optical properties, including a narrow
      emission band (full width at half maximum = 55 nm), an optimal quantum yield of
      32.5% and two-photon fluorescence. Furthermore, the bandgap of PAQD24 is highly
      sensitive toward pH variations in the near-neutral region, due to the proton
      doping and dedoping of the PANI structure. Such unique properties together with
      its fine bio-compatibility enable the application of this material as a turn-on
      fluorescent probe for the labeling of acidic biotargets from sub-cellular to
      organ levels, providing potential applications in diagnosis and surgery guidance
      for certain diseases.

PMID- 29582862
TI  - Photodynamic effect of zinc porphyrin on the promastigote and amastigote forms of
      Leishmania braziliensis.
AB  - Leishmaniasis is a neglected disease present in more than 88 countries. The
      currently adopted chemotherapy faces challenges related to side effects and the
      development of resistance. Photodynamic therapy (PDT) is emerging as a
      therapeutic modality for cutaneous leishmaniasis. Zn(ii) meso-tetrakis(N
      ethylpyridinium-2-yl)porphyrin (ZnTE-2-PyP4+, ZnP) is a cationic, water-soluble,
      zinc porphyrin-based photosensitizer whose photodynamic effect on Leishmania
      braziliensis was analyzed by evaluating the number of visibly undamaged and
      motile cells, cell membrane integrity, mitochondrial membrane potential, and
      ultrastructural damage. Treatment of parasites with ZnP and light induced damage
      in up to 90% of L. braziliensis promastigote cells. Propidium iodide labeling
      suggested the loss of plasma membrane integrity. In samples treated with ZnP and
      light, a hyperpolarization of the mitochondrial membrane potential was also
      observed. Ultrastructural evaluation of promastigotes after photodynamic
      treatment indicated a loss of cytoplasmic material and the presence of vacuoles.
      Scanning electron microscopy showed wrinkling of the plasma membrane and a
      reduced cell volume. Additionally, the number of amastigotes per macrophage was
      reduced by about 40% after photodynamic application. The treatment showed no
      considerable toxicity against mammalian cells. Therefore, the results indicated
      that PDT associated with ZnTE-2-PyP4+ represents a promising alternative to
      cutaneous leishmaniasis treatment.

PMID- 29582871
TI  - A stable layered P3/P2 and spinel intergrowth nanocomposite as a long-life and
      high-rate cathode for sodium-ion batteries.
AB  - Layered sodium transition-metal oxides, NaxMeO2, with large theoretical capacity
      are regarded as an important class of cathode materials for sodium-ion batteries
      (SIBs). However, they usually exhibit inferior thermodynamic stability and
      sluggish Na+ kinetics due to the unwanted phase transitions and large Na+-ionic
      radius. In this work, considering the beneficial synergistic effects of layered
      P2/P3 and Fd3[combining macron]m spinel phases, a stable layered/spinel
      intergrowth nanocomposite Na0.5[Ni0.2Co0.15Mn0.65]O2 is rationally designed and
      successfully prepared via a co-precipitation route and a subsequent solid-state
      reaction, and the triphase synergy in this layered/spinel nanocomposite is
      demonstrated. In Na/Na0.5[Ni0.2Co0.15Mn0.65]O2 half-cells, it delivers a high
      specific capacity of ~180 mA h g-1 and a good cycling stability, with a capacity
      retention of 87.6% after 100 cycles, at a rate of 0.1C between 1.5 and 4.0 V (vs.
      Na/Na+). The large reversible capacity of 105 mA h g-1 is also achieved even at a
      high rate of 10C, indicating high-rate capability. Besides, the full-cells using
      this nanocomposite as the cathode and hard carbon as the anode exhibit long-term
      cycle-life and high-power properties, indicating the expected merits of
      layered/spinel mixed phases. The superior sodium storage performance of this
      layered P3/P2 and spinel intergrowth nanocomposite makes it a promising candidate
      as a long-life and high-rate cathode for SIBs.

PMID- 29582873
TI  - Persulfate-promoted oxidative C-N bond coupling of quinoxalinones and NH
      sulfoximines.
AB  - The persulfate-meditated oxidative C-N bond coupling of the C-H bond of
      quinoxalinones and the N-H bond of NH-sulfoximines is reported. The reaction
      proceeds smoothly under transition metal-free conditions and provides good to
      excellent yields of sulfoximidoyl-functionalized quinoxalinone products under
      mild conditions. The optimized conditions were found to be suitable for a range
      of sulfoximine and quinoxalinone substrates. This reaction offers a new and
      convenient strategy to directly install the sulfoximine moiety into the C3
      position of quinoxalinone.

PMID- 29582875
TI  - Facile synthesis of a two-photon fluorescent probe based on pyrimidine 2
      isothiocyanate and its application in bioimaging.
AB  - Two-photon microscopy imaging has been widely applied in biological imaging, but
      the development of two-photon absorption probes is obviously lagging behind in
      the development of imaging technology. In this paper, a two-photon fluorescent
      probe (1) based on pyrimidine 2-isothiocyanate has been designed and synthesized
      through a simple method for two-photon biological imaging. Probe 1 was able to
      couple effectively with the amino groups on biomolecules. To verify the
      reactivity of the isothiocyanate group on probe 1 and the amine groups on the
      biomolecules, d-glucosamine was chosen as a model biomolecule to conjugate with
      probe 1. The result showed that probe 1 could effectively conjugate with d
      glucosamine to synthesize probe 2, and the yield of probe 2 was 83%. After
      conjugating with d-glucosamine, linear absorption spectra, single-photon
      fluorescence spectra, and two-photon fluorescence spectra of probes 1 and 2 did
      not present significant changes. Probes 1 and 2 exhibited high fluorescence
      quantum yields (0.71-0.79) in toluene and chloroform. They also exhibited
      different photo-physical properties in solvents with different polarities. The
      two-photon absorption cross-section of probe 1 was 953 GM in toluene. In
      addition, probe 1 could be effectively conjugated with transferrin, and the
      conjugated probe (Tf-1) could be transported into Hep G2 cells through a receptor
      mediated process for biological imaging. These results demonstrate that such
      probes are expected to have great potential applications in two-photon
      fluorescence bioimaging.

PMID- 29582876
TI  - Appropriate strategies for South Africa for the management of acute myocardial
      infarction in patients presenting with ST-segment elevation.

PMID- 29582877
TI  - The proportion of South Africans living within 60 and 120 minutes of a
      percutaneous coronary intervention facility.
AB  - INTRODUCTION: Timely reperfusion, preferably via percutaneous coronary
      intervention (PCI) following myocardial infarction, improves mortality rates.
      Emergency medical services play a pivotal role in recognising and transporting
      patients with ST-elevation myocardial infarction directly to a PCI facility to
      avoid delays to reperfusion. Access to PCI is, in part, dependant on the
      geographic distribution of patients around PCI facilities. The aim of this study
      was to determine the proportion of South Africans living within 60 and 120
      minutes of a PCI facility. METHODS: PCI facility and population data were
      subjected to proximity analysis to determine the average drive times from
      municipal ward centroids to PCI facilities for each province in South Africa.
      Thereafter, the population of each ward living within 60 and 120 minutes of a PCI
      facility was extrapolated. RESULTS: Approximately 53.8 and 71.53% of the South
      African population live within 60 and 120 minutes of a PCI facility. The median
      (IQR, range) drive times and distances to a PCI facility are 100 minutes (120.4
      min, 0.7-751.8) across 123.6 km (157.6 km, 0.3-940.8). CONCLUSION: Based on the
      proximity of South Africans to PCI facilities, it seems possible that most
      patients could receive timely PCI within 120 minutes of first medical contact.
      However, this may be unlikely for some due to a lack of medical insurance, under
      developed referral networks or other system delays. Coronary care networks should
      be developed based on the proximity of communities to 12-lead ECG and reperfusion
      therapies (such as PCI facilities). Public and private healthcare partnerships
      should be fortified to allow for patients without medical insurance to have equal
      accesses to PCI facilities.

PMID- 29582878
TI  - Value of transluminal attenuation gradient of stress CCTA for diagnosis of
      haemodynamically significant coronary artery stenosis using wide-area detector CT
      in patients with coronary artery disease: comparison with stress perfusion CMR.
AB  - INTRODUCTION: This study aimed to evaluate the value of transluminal attenuation
      gradient (TAG) of stress coronary computed tomography angiography (CCTA), using a
      wide-area detector CT in patients with coronary artery disease, compared to
      stress perfusion cardiac magnetic resonance (CMR) imaging. METHODS: This
      prospective study from May 2012 to January 2015 included 21 patients with
      moderate coronary stenosis on invasive coronary angiography. All patients
      underwent adenosine stress single-shot CCTA with a rest CCTA scan using a wide
      area detector CT. Coronary artery stenosis was evaluated on both stress and rest
      CCTA images, and TAG was manually obtained for all vessels. Stress perfusion CMR
      was used as a reference standard. A TAG cut-off value of -15.1 HU/10 mm was
      applied for diagnosing haemodynamically significant stenosis. The diagnostic
      accuracies of TAG and CMR were estimated and compared. RESULTS: TAG of stress
      CCTA in all coronary arteries had a sensitivity, specificity, and positive and
      negative predictive values of 90.5, 90.0, 86.4 and 93.1%, respectively.
      Corresponding values for TAG of rest CCTA in all coronary arteries were 42.9,
      83.3, 64.3 and 67.6%, respectively, whereas those for TAG of coronary arteries
      with moderate stenosis on stress CCTA were 93.3, 100, 100 and 92.3%,
      respectively. Mean effective radiation doses for stress and rest CCTA were 10.6
      +/- 2.6 mSv and 2.3 +/- 1.3 mSv, respectively. CONCLUSION: TAG of CCTA provided
      high diagnostic accuracy for detecting haemodynamically significant coronary
      artery stenosis. TAG of stress CCTA was more diagnostically accurate, especially
      in coronary arteries with moderate stenosis.

PMID- 29582879
TI  - Short-term rehospitalisation or death and determinants after admission for acute
      heart failure in a cohort of African patients in Port Harcourt, southern Nigeria.
AB  - BACKGROUND: Heart failure (HF) is a major health burden globally and contributes
      significantly to morbidity and mortality related to cardiovascular disease. The
      aim of this study was to determine the outcome, and factors determining these
      outcomes in patients admitted for acute HF and followed up for six months.
      METHOD: This was a hospital-based, prospective study. Subjects included
      consecutive patients with a confirmed diagnosis of acute HF admitted to the
      medical wards of the University of Port Harcourt Teaching Hospital (UPTH) in
      Nigeria over one year. All had a full physical examination and relevant
      investigations, including echocardiography. Subjects were followed up for six
      months and reassessed for outcome/endpoint, which was rehospitalisation or death.
      Factors that predicted these outcomes were also determined. RESULTS: There were
      160 subjects, 84 females and 76 males, age range 20 to 87 years, mean age 52.49
      +/- 13.89 years. Sixteen subjects (10.0%) were lost to follow up, 66 (41.3%)
      showed clinical improvement, 57 (35.6%) were rehospitalised, while 21 (13.1%)
      died. Determinants of rehospitalisation were New York Heart Association (NYHA)
      class, heart failure type, haemoglobin level at presentation and estimated
      glomerular filtration rate (eGFR). Determinants of mortality were NYHA class and
      haemoglobin level at presentation. CONCLUSION: Heart failure rehospitalisation
      and mortality rates of 35.6 and 13.1%, respectively, were high compared to
      developed countries.

PMID- 29582881
TI  - Risk assessment of the occurrence of sudden death related to hypertrophic
      cardiomyopathy in Dakar.
AB  - AIM: The aim of this study was to assess of the risk of sudden death in a
      population of hypertrophic cardiomyopathy patients in Dakar. METHODS: This was a
      transverse study at the cardiology clinic of Aristide Le Dantec Hospital from
      January 2014 to June 2015. We used the European Society of Cardiology risk score
      to calculate this risk. RESULTS: The average age of patients was 53 years.
      Unexplained syncope was found in two patients and two others had a family history
      of sudden death. The septal hypertrophy average was 20.9 mm. Seven patients had
      left intraventricular obstruction. One patient had a high risk of sudden death,
      three had intermediate risk and 13 had low risk. Competitive sport was not
      allowed, 13 patients were under medical treatment, one had an implantable
      cardioverter defibrillator and two had no treatment. CONCLUSION: Our study
      highlighted a low and intermediate risk of the occurrence of sudden death at five
      years. One patient had a high risk of sudden death.

PMID- 29582882
TI  - Coronary artery bypass grafting and paraparesis; is there a correlation?
AB  - Adult cardiac surgery is associated with significant perioperative morbidity and
      mortality rates, mainly in elderly patients with co-morbidities. A series of
      postoperative complications may arise and delay the recovery of patients
      undergoing cardiac surgery. Such complications also increase the burden of
      resource use and may affect late survival rates. Neurological complications
      appear mainly as stroke of varying degrees, with impairment of mobility and
      ability of the patient. We describe a rare case of progressive paraparesis after
      on-pump coronary artery bypass grafting, and review its aetiology, diagnosis and
      management.

PMID- 29582880
TI  - Left ventricular remodelling in chronic primary mitral regurgitation:
      implications for medical therapy.
AB  - Surgical repair or replacement of the mitral valve is currently the only
      recommended therapy for severe primary mitral regurgitation. The chronic
      elevation of wall stress caused by the resulting volume overload leads to
      structural remodelling of the muscular, vascular and extracellular matrix
      components of the myocardium. These changes are initially compensatory but in the
      long term have detrimental effects, which ultimately result in heart failure.
      Understanding the changes that occur in the myocardium due to volume overload at
      the molecular and cellular level may lead to medical interventions, which
      potentially could delay or prevent the adverse left ventricular remodelling
      associated with primary mitral regurgitation. The pathophysiological changes
      involved in left ventricular remodelling in response to chronic primary mitral
      regurgitation and the evidence for potential medical therapy, in particular beta
      adrenergic blockers, are the focus of this review.

PMID- 29582883
TI  - Editorial: Orthogeriatrics and Hip Fractures.

PMID- 29582885
TI  - Insulin Resistance is Associated with Chronic Laryngitis in Korean Women.
AB  - OBJECTIVES: The aim of this study was to investigate the association between
      chronic laryngitis (CL) and insulin resistance (IR) in South Korea using data
      from the 2010 Korea National Health and Nutrition Examination Surveys (KNHANES).
      DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data of 4,261 adults who
      completed KNHANES were analyzed. CL was considered when participants experienced
      a voice change and demonstrated flexible laryngoscopic findings of diffuse
      laryngeal inflammation. All participants were assessed for IR using the
      homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Among the
      Korean population older than 19 years, the prevalence of chronic laryngitis was
      3.8+/-0.7%. Univariate analysis demonstrated that CL was significantly associated
      with smoking and systolic and diastolic blood pressure in men and with age,
      diastolic blood pressure, HDL cholesterol, insulin, and HOMA-IR in women.
      Multiple regression analysis demonstrated that the mean value of HOMA-IR was
      significantly associated with CL in women only. In addition, CL was more
      prevalent in the highest compared with the lowest HOMA-IR quartile (OR [95% CI]:
      2.268 [1.053-4.884] after adjusting for age, OR [95% CI]: 2.235 [1.040-6.181]
      after adjusting for confounding factors of age, body mass index, smoking status,
      alcohol intake, regular exercise, education, and income). CONCLUSIONS: These
      findings indicate that IR characterized by HOMA-IR is significantly associated
      with CL in Korean women only. Our results suggest that HOMA-IR could be an early
      predictive factor of increased risk of CL in Korean women.

PMID- 29582884
TI  - Involvement of Advanced Practice Nurse in the Management of Geriatric Conditions:
      Examples from Different Countries.
AB  - The increasing demand for healthcare services is placing great strain on
      healthcare systems throughout the world. Although the older population is
      increasing worldwide, there is a marked deficit in the number of persons trained
      in geriatrics. It is now recognized that early detection and treatment of
      geriatric conditions (e.g., frailty, sarcopenia, falls, anorexia of aging, and
      cognitive decline) will delay or avert the development of disability. At the same
      time, recent years have seen an increased interest and use of advanced practice
      nurses (APN). Models of best practices of supervision and collaboration have been
      promulgated by many organizations. APN's roles and scope of practice have been
      expanded in many countries and the quality and cost-effectiveness of healthcare
      systems have improved. Nevertheless, in older people, evidence of advanced
      practice roles remains scattered, and there is little synthesis of evidence, and
      therefore it is not easy to visualize the different practice models and their
      components. The aim of this paper is to explain the need for advanced practice
      nurses to manage geriatric conditions.

PMID- 29582886
TI  - Smoking Predicting Physical Activity in an Aging America.
AB  - OBJECTIVES: Tobacco smoking and physical inactivity are among leading behavioral
      risk factors for ill health in older adults. This study considers how smoking is
      associated with physical activity. DESIGN: Using a Life-Course model, data are
      analyzed regarding this relationship, controlling for, and interacted with, life
      course and other factors. Daily smokers and sometimes smokers were hypothesized
      to engage in less leisure-time physical activity than those who never smoked,
      while those who stopped smoking were expected to do more than never smokers.
      Analyses were performed using SAS-Callable SUDAAN. SETTING AND PARTICIPANTS:
      Secondary data from ten years of a national sample of adults aged 18 and over of
      the National Health Interview Survey, 2001-2010, are used (N = 264,945, missing
      data excluded, of 282,313 total cases). MEASUREMENTS: Daily smokers, occasional
      smokers, and smoking quitters are compared to never smokers with regard to
      requisite physical activity (150 minutes per week of moderate, 100 of vigorous,
      and/or 50 of strengthening activity). Life-course measures include birth cohorts,
      age, and year of survey, as well as gender, race/ethnicity, and education.
      RESULTS: Overall, hypotheses are supported regarding daily smokers and quitters;
      but the hypothesis is strongly rejected among sometimes smokers, who are much
      more likely to do requisite physical activity. Findings differ by age, sometimes
      smokers age 65 and over being less likely to do physical activity. Findings among
      all men are similar to the overall findings, while those among all women are
      similar to those for older respondents. Associations of smoking status with
      physical activity vary greatly by race/ethnicity. CONCLUSIONS: Daily smokers may
      be most in need of both smoking cessation and leisure-time physical activity
      interventions. Smoking-cessation efforts may pay greater physical activity
      benefits among women and the aged, while smoking-reduction efforts may provide
      better outcomes among men. Smoking reduction efforts may pay more exercise
      benefits among African-Americans and Hispanics.

PMID- 29582887
TI  - Cardiorespiratory Adaptations in Elderly Men Following Different Concurrent
      Training Regimes.
AB  - BACKGROUND: This study aimed to investigate the effects of different intra
      session exercise orders during concurrent training (CT) on endurance performance
      in elderly men, as well as to verify its influence on individual responses in
      endurance performance. DESIGN: Twenty-five healthy elderly men (64.7 +/- 4.1
      years) were placed into two groups: strength training prior to endurance training
      (SE, n=13), and one in the reverse order (ES, n=12). CT was performed three times
      a week during 12 weeks. Before and after training, peak oxygen uptake (VO2peak),
      maximal workload (Wmax), absolute and relative cycling economy at 25, 50, 75 and
      100 W (i.e., average VO2 at different stages) were assessed. RESULTS: Similar
      increases in VO2peak were observed in the SE and ES groups (SE: 8.1 +/- 9.9%; ES:
      9.3 +/- 9.8%; P<0.001), as well as in Wmax (SE: 19.9 +/- 19.3%; ES: 24.1 +/-
      24.0%; P<0.001). Moreover, significant reductions were observed in the absolute
      VO2 at 100 W (P<0.05) in the SE and ES groups. No difference between groups was
      observed. In the ES group, one subject did not respond positively in terms of
      both VO2max and Wmax, whereas 4 subjects did not respond positively in terms of
      both VO2max and Wmax in SE group. CONCLUSIONS: CT improved maximal and submaximal
      endurance performance in elderly men, independent of intra-session exercise
      order. However, it seems that the ES order elicited more individual
      responsiveness in terms of maximal endurance performance than SE order.

PMID- 29582888
TI  - Intake of 25-Hydroxyvitamin D3 Reduces Duration and Severity of Upper Respiratory
      Tract Infection: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group
      Comparison Study.
AB  - OBJECTIVES: This study aimed to assess the effect of 25-hydroxyvitamin D3 (25OHD)
      which is a hydroxide of vitamin D3 ingestion on upper respiratory tract infection
      (URTI). DESIGN AND SETTING: A prospective, randomized, double-blind, placebo
      controlled study was performed from December 2015 to September 2016 in the
      Nihonbashi Egawa Clinic, Kei Medical Office TOC Building Medical Clinic, and
      Medical Corporation Kaiseikai Kita-Shinyokohama Medical Clinic, in Japan.
      PARTICIPANTS: Four hundred twenty eight participants aged 45-74 years were
      screened by their serum 25-hydoroxyvitamin D concentration. INTERVENTION: The
      participants were randomized to either 25OHD (10 MUg/day) or placebo capsule,
      daily, for 16 consecutive weeks. MEASUREMENTS: The primary outcome measure was
      the incidence proportion of URTI, and the secondary outcome measures were the
      physical severity score, the quality-of-life (QOL) score, the duration of URTI,
      and the incidence proportion of new URTI events every four weeks. Data were
      collected using cold diary Wisconsin Upper Respiratory Symptom Survey-21 (WURSS
      21) during the intervention. RESULTS: Of 428 participants screened, 252 with
      serum 25-hydroxyvitamn D levels were deficient or insufficient (75 nmol/L or
      less) were enrolled in this study. Of these, 105 placebo and 110 25OHD group
      subjects completed the study. For the incidence proportion of URTI, no effect of
      25OHD intake was observed. On the other hand, the duration of URTI was shorter in
      the 25OHD (P = 0.061) compared to placebo. For the incidence proportion of URTI
      every four weeks, the incidence of new URTI was decreased in both groups over the
      time of intake. However, when the 25OHD and the placebo were compared, a decrease
      in the incidence proportion of URTI was seen earlier in the 25OHD. When the total
      physical severity score and the total QOL score during the study were assessed,
      they both were significantly improved in the 25OHD compared to placebo.
      CONCLUSIONS: The intake of 25OHD may reduce the duration of URTI, the physical
      severity, and the QOL when suffering from URTI.

PMID- 29582889
TI  - Muscle Weakness and Physical Disability in Older Americans: Longitudinal Findings
      from the U.S. Health and Retirement Study.
AB  - IMPORTANCE: Muscle weakness is an important indicator of disability, chronic
      disease and mortality. While we recently proposed sex/race specific grip strength
      cutpoints for clinical muscle weakness in a diverse, nationally representative
      sample of older Americans, the extent to which these cutpoints predict physical
      disability remains unknown. OBJECTIVE: To examine whether sex/race specific
      muscle weakness cutpoints predict physical disability status in a nationally
      representative sample of Americans age 65+. DESIGN: We used data from the 2006
      2010 Health and Retirement Study. Fully-adjusted, weighted multinomial logistic
      regression models were used to quantify the odds of experiencing the onset,
      progression or persistence of disability in activities of daily living (ADL)
      among weak versus non-weak individuals over a 2-year period. SETTING: General
      community, nationally representative sample of older Americans. PARTICIPANTS:
      Population-based, community dwelling sample of older American adults aged 65
      years+; 57 percent were women, 91% were White and the mean age was 75 years. Main
      Outcome(s) and Measure(s): The primary outcome of interest was disability
      dynamics, defined by changes in ADL status across at 2- year period. The primary
      exposure was clinical muscle weakness as defined by previously identified
      cutpoints. Hypotheses were formulated before analyses were conducted. RESULTS: In
      this nationally representative sample (n= 8,725), 44% of individuals were
      classified as weak at baseline. At follow-up, 55% remained independent with no
      change in their ADL status, 11% had an onset of disability and 4% progressed in
      their disability status. The odds of experiencing an onset of ADL disability was
      54% higher among weak individuals compared those who were not weak at baseline
      (OR= 1.54, 95% CI= 1.54, 1.5, p<.0001); the odds of experiencing a progression in
      physical disability status was 2.16 times higher among those who were weak at
      baseline compared to non-weak individuals (OR= 2.16, 95% CI= 2.15, 2.16,
      p<.0001). CONCLUSIONS: This is the first study to use grip strength weakness cut
      points to identify those who may be at greatest risk for experiencing physical
      disability in later life. Results underscore the importance of using population
      specific cutpoints for clinical weakness in order to identify individuals at
      greatest risk for adverse health outcomes.

PMID- 29582890
TI  - Association between Serum Uric Acid Level and Carotid Atherosclerosis in Chinese
      Individuals Aged 75 Years or Older: A Hospital-Based Case-Control Study.
AB  - OBJECTIVES: To investigate the association between serum uric acid level and the
      presence and progression of carotid atherosclerosis in Chinese individuals aged
      75 years or older. DESIGN: Case-control study. SETTING: In a teaching hospital.
      PARTICIPANTS: Five hundred and sixty-four elderlies (75 years or above) who
      underwent general health screening in our hospital were enrolled. MEASUREMENTS:
      The detailed carotid ultrasound results, physical examination information,
      medical history, and laboratory test results including serum uric acid level were
      recorded, these data were used to analyze the relationship between serum uric
      acid level and carotid atherosclerosis. Then, subjects who underwent the second
      carotid ultrasound 1.5-2 years later were further identified to analyzed the
      relationship between serum uric acid and the progression of carotid
      atherosclerosis. RESULTS: A total of 564 subjects were included, carotid plaque
      was found in 482 (85.5%) individuals. Logistic regression showed that subjects
      with elevated serum uric acid (expressed per 1 standard deviation change) had
      significantly higher incidence of carotid plaque (odds ratio, 1.37; 95%
      confidence interval, 1.07-1.75; P= 0.012) after controlling for other factors. A
      total of 236 subjects underwent the follow-up carotid ultrasound. Linear
      regression showed that serum uric acid level (expressed per 1 standard deviation
      change; 1 standard deviation = 95.5 MUmol/L) was significantly associated with
      percentage of change of plaque score (P = 0.008). Multivariable linear regression
      showed that 1 standard deviation increase in serum uric acid levels was expected
      to increase 0.448% of plaque score (P = 0.023). CONCLUSION: The elevated serum
      uric acid level may be independently and significantly associated with the
      presence and progression of carotid atherosclerosis in Chinese individuals aged
      75 years or older.

PMID- 29582891
TI  - Age and IQ Explained Working Memory Performance in a RCT with Fatty Fish in a
      Group of Forensic Inpatients.
AB  - OBJECTIVES: To investigate the effect of a long-term fatty fish intervention on a
      pure cognitive mechanism important for self-regulation and mental health, i.e.
      working memory (WM), controlling for age and IQ. DESIGN: A randomized controlled
      trial. SETTING: A forensic facility. PARTICIPANTS: Eighty-four young to middle
      aged male forensic inpatients with psychiatric disorders. INTERVENTION:
      Consumption of farmed salmon or control meal (meat) three times a week during 23
      weeks. MEASUREMENT: Performance on WM tasks, both accuracy and mean reaction
      time, were recorded pre and post intervention. RESULTS: Performance on a
      cognitive functioning tasks taxing WM seemed to be explained by age and IQ.
      CONCLUSION: Fatty fish consumption did not improve WM performance in a group of
      young to middle aged adults with mental health problems, as less impressionable
      factors such as aging and intelligence seemed to be the key components. The
      present study improves the knowledge concerning the interaction among nutrition,
      health and the aging process.

PMID- 29582892
TI  - Frequency of Hospital Use Before and After Home-Delivery Meal by Meals On Wheels,
      of Tarrant County, Texas.
AB  - BACKGROUND: Patients recently discharged from the hospital are vulnerable and are
      at high risk for readmission. Home-delivered meals may be beneficial in improving
      their health and facilitating independent living in the community. The purpose of
      this study was to identify the association between home-delivered meals and use
      of hospital services. METHODS: This study includes 120 clients recently
      discharged from an inpatient hospital stay or from an emergency department (ED)
      visit who received meal services from Meals On Wheels, Inc., of Tarrant County.
      Healthcare utilization data was extracted from the Dallas-Fort Worth Hospital
      Council Foundation, a regional all claims database used by over 90% of hospitals
      in Dallas-Fort Worth area. Signed tests and generalized linear models (GLM) were
      performed. RESULTS: A total of 16,959 meals were delivered from March 2013
      through March 2014. Each client received an average of 6.19 meals per week. The
      average number of ED visits decreased from 5.03 before receipt of meals to 1.45
      after receipt of meals, z = -5.23, p < .001. The average number of
      hospitalizations decreased from 1.33 to .83, z = -7.29, p < .001. The average
      length of stay per hospitalization decreased from 5.47 days to 2.34 days, z = 
      5.84, p < .001. Clients who received more meals were less likely to experience ED
      visits and hospitalizations after controlling for demographic characteristics and
      levels of physical functioning. CONCLUSION: The findings of this study indicate
      that home-delivered meals services may contribute to a reduction in hospital
      based care services among frail and vulnerable adults. Additional studies should
      consider the short and long-term effects of home-delivered meals services on
      healthcare utilization and the potential to decrease healthcare costs.

PMID- 29582893
TI  - Fat Quality Index and Risk of Cardiovascular Disease in the Sun Project.
AB  - OBJECTIVES: To examine the association between a dietary fat quality index (FQI),
      and the risk of incident cardiovascular events or deaths in the Seguimiento
      Universidad de Navarra (SUN) cohort. DESIGN: Longitudinal analysis during 10.1
      years of median follow-up. Cox models were used to estimate adjusted hazard
      ratios (HR) of incident cardiovascular diseases (CVD) according to tertiles of
      FQI and of different fat subtypes. SETTING: University of Navarra, Spain.
      PARTICIPANTS: 19,341 middle-aged adults. MEASUREMENTS: Fat intake was measured
      with a validated food-frequency questionnaire. The FQI was calculated according
      to the ratio: (monounsaturated+polyunsaturated) / (saturated+trans fatty acids).
      RESULTS: We observed 140 incident cases of CVD. No association was found for FQI
      (HR=0.94, 95 %CI 0.61-1.47 for the highest vs the lowest tertile, p for
      trend=0.884). No significant associations were found for different dietary fat
      subtypes on CVD risk. The results suggest no clear association between a higher
      FQI and a higher amount of energy from fat and incidence of CVD (p for
      interaction: 0.259 and p for trend only among participants with a percentage of
      energy from fat >=35% of total energy: 0.272). CONCLUSION: In this Mediterranean
      cohort, the FQI was not associated with cardiovascular events. A "heart-healthy
      diet" should focus its attention on dietary fat sources and should use an overall
      dietary pattern approach, rather than limiting the focus on fat subtypes. More
      research is needed to validate dietary advice on specific fatty acids intake or
      saturated fatty acids replacements for reducing CVD risk.

PMID- 29582894
TI  - Sex Differences in the Associations between L-Arginine Pathway Metabolites,
      Skeletal Muscle Mass and Function, and their Responses to Resistance Exercise, in
      Old Age.
AB  - OBJECTIVES: The current study was designed to explore the associations between L
      arginine metabolites and muscle mass and function in old age, which are largely
      unknown. DESIGN: The study used a randomised, double-blind, placebo-controlled
      design. SETTING: The study was carried out in a laboratory setting. PARTICIPANTS:
      50 healthy older adults [median age 70 years (IQR 67-73); 27 males].
      INTERVENTION: Participants undertook an 18-week resistance exercise program, and
      a nutritional intervention (fish oil vs. placebo). MEASUREMENTS: Serum
      homoarginine, ornithine, citrulline, asymmetric dimethylarginine (ADMA), NG
      monomethyl-L-arginine (L-NMMA), and symmetric dimethylarginine (SDMA), maximal
      voluntary contraction (MVC) and isokinetic torque of the knee extensors at 30
      degrees  s-1 (MIT), muscle cross sectional area (MCSA) and quality (MQ) were
      measured at baseline and after the intervention. RESULTS: No significant exercise
      induced changes were observed in metabolite concentrations. There were
      significant sex differences in the associations between metabolites and muscle
      parameters. After adjusting for age, glomerular filtration rate and fish oil
      intervention, citrulline (P=0.002) and ornithine (P=0.022) were negatively
      associated with MCSA at baseline in males but not females. However, baseline
      citrulline was negatively correlated with exercise-induced changes in MVC
      (P=0.043) and MQ (P=0.026) amongst females. Furthermore, amongst males, baseline
      homoarginine was positively associated with exercise-induced changes in MVC
      (P=0.026), ADMA was negatively associated with changes in MIT (P=0.026), L-NMMA
      (p=0.048) and ornithine (P<0.001) were both positively associated with changes in
      MCSA, and ornithine was negatively associated with changes in MQ (P=0.039).
      CONCLUSION: Therefore, barring citrulline, there are significant sex differences
      in the associations between L-arginine metabolites and muscle mass and function
      in healthy older adults. These metabolites might enhance sarcopenia risk
      stratification, and the success of exercise programs, in old age.

PMID- 29582895
TI  - "Feeling More Self-Confident, Cheerful and Safe". Experiences from a Health
      Promoting Intervention in Community Dwelling Older Adults - A Qualitative Study.
AB  - OBJECTIVES: Studies show that regular exercise in combination with nutritional
      support can be effective in managing sarcopenia, which is age-related involuntary
      loss of skeletal muscle mass and strength. Qualitative investigations of
      participants' experiences from interventions in this domain are scarce. In this
      study, we explored older persons' experiences from an intervention designed to
      prevent sarcopenia, with the aim of capturing the participants' thoughts and
      opinions. DESIGN: A qualitative study embedded in the multicenter randomized
      clinical trial The Vitality and Vigor in the Elderly study, VIVE2. Focus group
      interviews were conducted. Manifest and latent content analyses were performed.
      PARTICIPANTS: Community dwelling older adults (n=20) 71-86 years of age with
      minor limitations in mobility. RESULTS: The experiences from the intervention
      were categorized and interpreted in one overall theme "Feeling more self
      confident, cheerful and safe". The theme encompasses the categories psychological
      effects of participating in the intervention, physical effects of participating
      in the intervention, the importance of social support and the importance of a
      tailored set-up. The participants described their motives for participating in
      the intervention as being based on concerns regarding the negative health effects
      of continuing a sedentary lifestyle, difficulties of getting started on their own
      and lack of confidence in accomplishing change on their own. Participants also
      expressed that one main objective for participating was to lose weight.
      CONCLUSION: In this study we have captured the experiences of older adults with
      minor mobility limitations who participated in a lifestyle intervention. The
      experiences are interpreted in one overall theme "Feeling more self-confident,
      cheerful and safe". The central understanding of the participants' experiences
      was that the intervention affected them in several ways, both psychologically and
      physically, and that supporting factors included the social support, which became
      a prerequisite for success. A noticeable finding was the discrepancy between the
      motive of the participants, to lose weight, and the aim of the study, to improve
      muscle function. The expectation to lose weight seems to reflect what is commonly
      known as to be healthy. To our knowledge, at least in Sweden, there are no
      campaigns or public information highlighting the risks of sarcopenia and the
      complex issue of if, and when weight loss is desirable for older individuals.
      This finding highlights the importance of providing such information to this
      target group. The findings in this study provide valuable knowledge for research
      teams, practitioners and decision makers when designing and setting objectives
      for health-promoting interventions for older individuals.

PMID- 29582896
TI  - Cognitive Dysfunction in Urban-Community Dwelling Prefrail Older Subjects.
AB  - OBJECTIVES: A number of studies have reported that frailty is cross-sectionally
      associated with cognitive decline and is also a risk for future cognitive decline
      or dementia; however, there have been only a few studies that focus on the
      association between prefrailty and cognitive dysfunction. In the current study,
      we investigated the association between prefrailty and cognition. DESIGN: A cross
      sectional study of the data obtained at registration in a randomized control
      trial. SETTING: Toyota, Japan. PARTICIPANTS: Community-dwelling older subjects
      (male 54.6%) who had cognitive complaints. MEASUREMENTS: A battery of
      neuropsychological and physical assessments were performed. Prefrailty was
      defined as exhibiting one or two of the five Fried criteria (weight loss,
      exhaustion, weakness, slow gait speed and low physical activity). We performed a
      multiple regression analysis to investigate the associations of cognitive
      performance with prefrailty, adjusting for the factors that were significantly
      different between the robust and prefrailty groups. To assess the cognitive
      attributes that were significantly associated with prefrailty, logistic analysis
      was performed to see if one specific criterion of the five frailty criteria was
      associated with cognitive performance. RESULTS: The study subjects included 183
      prefrail and 264 robust individuals. The prefrail subjects with cognitive
      complaints were older, less educated, more depressive, and more likely to have
      diabetes mellitus than the robust subjects. The prefrail subjects had lower
      performance in a wide-range of cognitive domains, and after adjustments for age,
      education, depressive mood, and diabetes mellitus, prefrailty was associated with
      a decline in delayed memory and processing speed. Among the components of the
      Fried criteria, slow gait speed and loss of activity were significantly
      associated with slow processing speed as assessed by the digit symbol
      substitution test. CONCLUSION: The current results demonstrated that prefrailty
      was associated with worse memory and processing speed performance, but not with
      other cognitive domains.

PMID- 29582897
TI  - Dietary Restriction Ameliorates Age-Related Increase in DNA Damage, Senescence
      and Inflammation in Mouse Adipose Tissuey.
AB  - : Ageing is associated with redistribution of fat around the body and saturation
      of visceral adipose depots. Likewise, the presence of excess fat in obesity or
      during ageing places extra stress on visceral depots, resulting in chronic
      inflammation and increased senescence. This process can contribute to the
      establishment of the metabolic syndrome and accelerated ageing. Dietary
      restriction (DR) is known to alleviate physiological signs of inflammation,
      ageing and senescence in various tissues including adipose tissue. OBJECTIVES:
      Our pilot study aimed to analyse senescence and inflammation parameters in mouse
      visceral fat tissue during ageing and by short term, late-onset dietary
      restriction as a nutritional intervention. Design, measurements: In this study we
      used visceral adipose tissue from mice between 5 and 30 months of age and
      analysed markers of senescence (adipocyte size, gammaH2A.X, p16, p21) and
      inflammation (e.g. IL-6, TNFalpha, IL-1beta, macrophage infiltration) using
      immuno-staining, as well as qPCR for gene expression analysis. Fat tissues from 3
      mice per group were analysed. RESULTS: We found that the amount of gammaH2A.X
      foci as well as the expression of senescence and inflammation markers increased
      during ageing but decreased with short term DR. In contrast, the increase in
      amounts of single or aggregated macrophages in fat depots occurred only at higher
      ages. Surprisingly, we also found that adipocyte size as well as some senescence
      parameters decreased at very high age (30 months). CONCLUSIONS: Our results
      demonstrate increased senescence and inflammation during ageing in mouse visceral
      fat while DR was able to ameliorate several of these parameters as well as
      increased adipocyte size at 17.5 months of age. This highlights the health
      benefits of a decreased nutritional intake over a relatively short period of time
      at middle age.

PMID- 29582898
TI  - 8-Methoxypsoralen Plus Ultraviolet A Reduces the Psoriatic Response to Imiquimod
      in a Murine Model.
AB  - The effects of 8-Methoxypsoralen plus ultraviolet A (PUVA) or ultraviolet B (UVB)
      alone on imiquimod-induced psoriasis were examined in a mouse model. Mouse skin
      was treated with repetitive sub-phototoxic doses of PUVA or UVB before or during
      the induction of toll-like receptor 7/8 activation and psoriasis through the
      application of imiquimod. PUVA, to a greater degree than UVB, suppressed the
      established imiquimod-induced psoriatic phenotype, but pretreatment with PUVA
      prior to administration of imiquimod also reduced the susceptibility of murine
      skin to respond to imiquimod to a greater degree than did pretreatment with UVB.
      PUVA downregulated baseline levels of miRNA27a and 29a, as well as interferon
      gamma, interleukin-17 and -9, cytokines, which drive psoriatic inflammation.
      Microarray analysis showed enrichment of senescence pathway genes linked to
      upregulation of p16/p21 proteins after PUVA pretreatment. However, the anti
      psoriatic effect of PUVA was lost when there was an interval of 7 days between
      final exposure to PUVA and the start of administration of imiquimod. This
      indicated that (UVB and) PUVA diminished imiquimod-induced established psoriatic
      inflammation, but also primed the skin in favour of a reduced responsiveness to
      toll-like receptor activation.

PMID- 29582899
TI  - Knee-ankle-foot orthoses for treating posterior knee pain resulting from genu
      recurvatum: Efficiency, patients' tolerance and satisfaction.
AB  - OBJECTIVE: To assess the efficiency of knee-ankle-foot orthoses for treating
      painful genu recurvatum, and to determine users' tolerance and satisfaction.
      PATIENTS: Patients included in the study had a genu recurvatum during the stance
      phase, confirmed by a medical doctor on physical examination. A total of 27
      patients with 31 knee-ankle-foot orthoses were included. METHODS: The main
      outcome was scored on a verbal numerical rating scale (VNRS) before and at least
      3 months after a knee-ankle-foot orthosis was fitted, and scored on a verbal
      numerical pain rating scale (VRS). Secondary outcomes were rated with the Quebec
      User Evaluation of Satisfaction with assistive Technology (QUEST). RESULTS: After
      fitting the knee-ankle-foot orthosis, the median VNRS pain score decreased from
      85/100 to 25/100 (p <= 0.001) and the description of pain on the VRS decreased
      from "extreme" to "mild" (p <= 0.001). The QUEST total score was 4.0. CONCLUSION:
      Treating a painful genu recurvatum with a knee-ankle-foot orthosis reduced the
      pain efficiently whatever the patients' diagnosis, and high scores were obtained
      for patients' satisfaction.

PMID- 29582900
TI  - Developing a spinal cord injury rehabilitation service in Madagascar.
AB  - Rehabilitation for people with spinal cord injury in many low- and middle-income
      countries is not avail-able or is in the early stages of development. However,
      rehabilitation is recognized as crucial in order to optimize functional recovery
      and outcomes for patients with spinal cord injury. With an increasing incidence
      of spinal cord injury, the unmet need for rehabilitation is huge. This report
      describes the early development of a specialist rehabilitation service for spinal
      cord injury in Madagascar, one of the poorest countries in the world. The
      sustained input to an expanding rehabilitation team has led to reductions in
      avoidable complications. The input of the rehabilitation team has been welcomed
      by the neurosurgery department, which has recognized fewer delays in patients
      undergoing surgical treatments. Cost, lack of resources and trained staff, and
      poor understanding of disability continue to provide challenges. However, the
      development of the rehabilitation service using low technology, but with a high
      level of knowledge and systematic management, is a source of considerable pride.
      This development in Madagascar can be regarded as a model for spinal cord injury
      rehabilitation in other low-resource settings.

PMID- 29582901
TI  - Dimensionality and scaling properties of the Patient Categorisation Tool in
      patients with complex rehabilitation needs following acquired brain injury.
AB  - OBJECTIVE: To investigate the scaling properties of the Patient Categorisation
      Tool (PCAT) as an instrument to measure complexity of rehabilitation needs.
      DESIGN: Psychometric analysis in a multicentre cohort from the UK national
      clinical database. PATIENTS: A total of 8,222 patents admitted for specialist
      inpatient rehabilitation following acquired brain injury. METHODS: Dimensionality
      was explored using principal components analysis with Varimax rotation, followed
      by Rasch analysis on a random sample of n = 500. RESULTS: Principal components
      analysis identified 3 components explaining 50% of variance. The partial credit
      Rasch model was applied for the 17-item PCAT scale using a "super-items"
      methodology based on the principal components analysis results. Two out of 5
      initially created super-items displayed signs of local dependency, which
      significantly affected the estimates. They were combined into a single super-item
      resulting in satisfactory model fit and unidimensionality. Differential item
      functioning (DIF) of 2 super-items was addressed by splitting between age groups
      (<65 and >= 65 years) to produce the best model fit (chi2/df = 54.72, p = 0.235)
      and reliability (Person Separation Index (PSI) = 0.79). Ordinal-to-interval
      conversion tables were produced. CONCLUSION: The PCAT has satisfied expectations
      of the unidimensional Rasch model in the current sample after minor
      modifications, and demonstrated acceptable reliability for individual assessment
      of rehabilitation complexity.

PMID- 29582902
TI  - Pictures tell their own story.

PMID- 29582903
TI  - Myocardial infarction in a neonate.
AB  - Due to the lack of evidence-based guidelines, management strategies for neonatal
      MI should be individualized and administered largely at the discretion of
      responsible treating teams. Supportive care with a focus on preserving adequate
      circulation and antithrombotic therapy with a view to restoring vascular patency
      are the mainstays of treatment. Thrombolytic therapy of neonatal MI includes a
      chance to completely restore myocardial function. Understanding the resilience of
      the neonatal heart and mechanism of cardiac cell repair in neonates may spark
      novel treatment strategies for severe MI in the large number of affected
      individuals in an aging population.

PMID- 29582904
TI  - Hemophilia in focus.

PMID- 29582906
TI  - ?

PMID- 29582905
TI  - Hemophilia in focus.

PMID- 29582907
TI  - Health promotion for young patients with haemophilia.
AB  - : The haemophilia treatment centre of the Clinic for Children and Youth Medicine
      in Jena extends medical care by health-promotion measures, namely: health
      counselling, adjuvant exercise therapy and school sports. In addition to the
      regular medical checks at the treatment centre patients are examined regarding
      physical fitness, joint situation, quality of life in general and disease
      specific manner, as well as psycho-social and nutritional behaviour. Findings and
      medical results of the examinations are integrated into an individual advice on
      therapy, school sports, and health recommendations. This aimed at strengthening
      health-related resources and minimizing potential injuries. First long-term
      evaluation shows an increase of activity behaviour and physical fitness without
      increasing bleeding rate and maintained joint function. CONCLUSION: Combining
      functional prevention diagnostics and individual health counselling shows signs
      of improved patient's health knowledge, self-competence and physical fitness.

PMID- 29582908
TI  - Wishes and worries of haemophilia patients.
AB  - Haemophilia care in Germany has achieved a high level and enables the majority of
      patients to lead a largely normal life. The Bluter Betreuung Bayern e.V. (BBB)
      aims to improve health care and support for haemophilia patients. A questionnaire
      has been developed by BBB representatives to evaluate unmet medical needs from
      the patient perspective. It was sent to 290 haemophilia patients and/or their
      parents in Bavaria in November 2015. The response rate was 51.4 %: 66 children
      aged < 15 years (66.7 % severe), 30 patients 15-24 years (66.7 % severe), 26
      patients 25-44 years (80.8 % severe), 24 patients > 44 years (95.8 % severe).
      Prophylactic therapy in patients with severe haemophilia aged < 25 and >= 25
      years is given "always" in >= 80 % and > 60 %, respectively. Substitution therapy
      is mostly uncomplicated. Satisfaction with medical care is high. Chronic pain is
      a problem with increasing age. Patients aged 25-44 years worry least regarding
      future health, safety and availability of factor products, patients > 44 years
      most. Overall, 80-100 % of the patients from all age groups are interested in
      information on the current state of science. Offers of the BBB for psychosocial
      support in addition to the medical care seem to be helpful and needed in all age
      groups.

PMID- 29582909
TI  - Portuguese Haemophilia Registry.
AB  - National Patient Registries (NPR) have an important role in the management of
      haemophilia and other inherited bleeding disorders, representing powerful
      instruments to support healthcare and research. Computer software to assist the
      NPR is crucial, as it facilitates the introduction of the data from a national
      universe that will be centralized and merged into a unique location, thus
      ensuring a greater reliability and accuracy of the collected data, avoiding
      duplication of patients. In Portugal, despite the efforts and recognition of the
      need of a NPR, just recently the protocol for the establishment of the computer
      software to support the Portuguese National Registry of Haemophilia and other
      Congenital Coagulopathies (PorR H&CC) was approved. This paper aims to present
      this newly developed computerized solution, as well as to report the main
      variables and information that will be available. The development of this
      application, which includes a set of sociodemographic, clinical and treatment
      data, was based on the principles of WFH, and the database that supports the NPR,
      with anonymized data, is operated and maintained in accordance with the Data
      Protection Law. Currently, the first data are available on the application. Our
      focus now is to ensure more registries and continuous data entry in order to have
      complete information on the characterization of the haemophilia patient
      population in Portugal.

PMID- 29582910
TI  - Subchondral haematoma.
AB  - : Haemophilic arthropathy is a complex multifactorial disorder that poses
      significant challenges to both the treating haematologist and arthroplasty
      surgeon. Its pathogenesis is incompletely understood. Recent literature has
      concentrated on the toxic effects of iron and the characteristic inflammatory
      synovitis. Discussion of the role of subchondral bleeding in joint damage has
      been neglected. A case of haemophilic arthropathy with extensive evidence of
      subchondral bleeding and related osteochondral destruction is presented. RESULT:
      The relevance of this mechanical pathway in the future management of haemophilic
      arthropathy is discussed with reference to recent literature. CONCLUSION:
      Clinicians should consider its importance when deciding whether to manage
      patients expectantly or with prophylactic factor replacement.

PMID- 29582911
TI  - One Year with Methods Open.

PMID- 29582912
TI  - Single Subject (N-of-1) Research Design, Data Processing, and Personal Science.

PMID- 29582913
TI  - Heart Rate Variability Biofeedback Stress Relief Program for Depression*. A
      Replicated Single-Subject Design
AB  - BACKGROUND: Depressive disorders often have a chronic course and the efficacy of
      evidence-based treatments may be overestimated. OBJECTIVE: To examine the
      effectiveness of the Heart Rate Variability Stress Reduction Program (SRP) as a
      supplement to standard treatment in patients with depressive disorders. METHODS:
      The SRP was individually administered in eight weekly sessions. Seven
      participants completed the full protocol and were enrolled in a single-subject
      ABA multiple baseline experimental design. To perform interrupted time-series
      analyses, daily measures were completed in a diary (depression, resilience,
      happiness, heart coherence and a personalized outcome measure). RESULTS: Five out
      of seven patients improved in depressed mood and/or a personalized outcome
      measure. The effect of treatment was reversed in four patients during the
      withdrawal phase. One patient reliably improved on depression, whereas two
      patients recovered on autonomy and one on social optimism. No consistent
      relationship was found between the heart rate variability-related level of
      coherence and self-reported mood levels. CONCLUSIONS: The SRP is beneficial in
      some domains and for some patients. A prolonged treatment or continued home
      practice may be required for enduring effects. The intervention had more clinical
      impact on resilience-related outcome measures than on symptoms. The small sample
      size does not permit generalization of the results. We recommend future
      investigation of the underlying mechanisms of the SRP.

PMID- 29582915
TI  - Use of an Activity Tracker to Test for a Possible Correlation of Resting Heart
      Rate with Life Events. An N-of-1 Study of Participant-provided Data

PMID- 29582914
TI  - Are Nomothetic or Ideographic Approaches Superior in Predicting Daily Exercise
      Behaviors?
AB  - OBJECTIVES: The understanding of how stress influences health behavior can
      provide insights into developing healthy lifestyle interventions. This
      understanding is traditionally attained through observational studies that
      examine associations at a population level. This nomothetic approach, however, is
      fundamentally limited by the fact that the environment- person milieu that
      constitutes stress exposure and experience can vary substantially between
      individuals, and the modifiable elements of these exposures and experiences are
      individual-specific. With recent advances in smartphone and sensing technologies,
      it is now possible to conduct idiographic assessment in users' own environment,
      leveraging the full-range observations of actions and experiences that result in
      differential response to naturally occurring events. The aim of this paper is to
      explore the hypothesis that an ideographic N-of-1 model can better capture an
      individual's stress- behavior pathway (or the lack thereof) and provide useful
      person-specific predictors of exercise behavior. METHODS: This paper used the
      data collected in an observational study in 79 participants who were followed for
      up to a 1-year period, wherein their physical activity was continuously and
      objectively monitored by actigraphy and their stress experience was recorded via
      ecological momentary assessment on a mobile app. In addition, our analyses
      considered exogenous and environmental variables retrieved from public archive
      such as day in a week, daylight time, temperature and precipitation. Leveraging
      the multiple data sources, we developed prediction algorithms for exercise
      behavior using random forest and classification tree techniques using a
      nomothetic approach and an N-of-1 approach. The two approaches were compared
      based on classification errors in predicting personalized exercise behavior.
      RESULTS: Eight factors were selected by random forest for the nomothetic decision
      model, which was used to predict whether a participant would exercise on a
      particular day. The predictors included previous exercise behavior, emotional
      factors (e.g., midday stress), external factors such as weather (e.g.,
      temperature), and self-determination factors (e.g., expectation of exercise). The
      nomothetic model yielded an average classification error of 36%. The ideographic
      N-of-1 models used on average about two predictors for each individual, and had
      an average classification error of 25%, which represented an improvement of 11
      percentage points. CONCLUSIONS: Compared to the traditional one-size-fits-all,
      nomothetic model that generalizes population-evidence for individuals, the
      proposed N-of-1 model can better capture the individual difference in their
      stressbehavior pathways. In this paper, we demonstrate it is feasible to perform
      personalized exercise behavior prediction, mainly made possible by mobile health
      technology and machine learning analytics.

PMID- 29582916
TI  - Tracking Human Gut Microbiome Changes Resulting from a Colonoscopy.

PMID- 29582917
TI  - Results of a Long-term Computerized Self-quantification of Mental Performance,
      Sensorimotor Coordination and Emotional State.

PMID- 29582918
TI  - Maximum Entropy Approach in Dynamic Contrast-Enhanced Magnetic Resonance Imaging.
AB  - BACKGROUND: In the estimation of physiological kinetic parameters from Dynamic
      Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) data, the determination of
      the arterial input function (AIF) plays a key role. OBJECTIVES: This paper
      proposes a Bayesian method to estimate the physiological parameters of DCE-MRI
      along with the AIF in situations, where no measurement of the AIF is available.
      METHODS: In the proposed algorithm, the maximum entropy method (MEM) is combined
      with the maximum a posterior approach (MAP). To this end, MEM is used to specify
      a prior probability distribution of the unknown AIF. The ability of this method
      to estimate the AIF is validated using the Kullback-Leibler divergence.
      Subsequently, the kinetic parameters can be estimated with MAP. The proposed
      algorithm is evaluated with a data set from a breast cancer MRI study. RESULTS:
      The application shows that the AIF can reliably be determined from the DCE-MRI
      data using MEM. Kinetic parameters can be estimated subsequently. CONCLUSIONS:
      The maximum entropy method is a powerful tool to reconstructing images from many
      types of data. This method is useful for generating the probability distribution
      based on given information. The proposed method gives an alternative way to
      assess the input function from the existing data. The proposed method allows a
      good fit of the data and therefore a better estimation of the kinetic parameters.
      In the end, this allows for a more reliable use of DCE-MRI.

PMID- 29582919
TI  - A cross-sectional analysis of joint status and quality of life in children and
      adolescents with haemophilia in Romania.
AB  - BACKGROUND: Haemophilia is a congenital disorder of coagulation with high
      economic burden due to its requirement for an expensive, lifelong replacement
      therapy, with additional costs for the frequent complications and for the severe
      handicapping consequences. The objective of this cross-sectional study aimed at
      giving an insight into the health condition of young haemophiliacs in the absence
      of a regular prophylactic therapy. METHODS: It was conducted on a heterogeneous
      group of 37 children and adolescents (4-24 years of age), with similar on demand
      therapeutic regimen, coming from the whole country, focusing on the joint status
      by using the Haemophila Joint Health Score (HJHS) system and on quality of life
      (QoL) by using the EQ-5D-3L-Y questionnaire. RESULTS: The results revealed an
      impressive situation: 70.3 % with chronic arthropathy, 19 % with target joints,
      69 % with multiple joint involvement, mainly elbow (41 %) and knee (34 %), joint
      damage starting in the age group 6-12 years (18.18 % arthropathy vs. 96 % in the
      age group above 12 years). Joint score (6.67 +/- 7.92), gait score (0.75 +/-
      1.14) and HJHS (7.43 +/- 8.78) were highly correlated (r = 0.7, p = 0.001) with
      the annualised bleeding rate ABR (16.2 +/- 12.1). They impacted the QoL in all
      domains, also expressed by a VAS of 68.39 +/- 21.6. CONCLUSION: We concluded that
      in the situation of an international consensus that prophylactic replacement can
      prevent cost-effectively and cost-efficiently the deleterious joint damages, our
      study is supporting the introduction even of secondary and tertiary prophylaxis
      in young patients in our country.

PMID- 29582920
TI  - Follow-up of a 6-month Programmed Sports Therapy (PST) in patients with
      haemophilia.
AB  - Studies describe benefits of exercise in Patients with haemophilia (PwH), but
      research on training sustainability is rare. Aim of this study was to observe the
      follow-up of a guided 6-month training intervention in PwH. This study included
      28 PwH after a training intervention (RCT) over 6 months. N=17 continued training
      (TC), N=11 stopped training (TS) after the study time. Strength measurements and
      subjective physical performance were tested.The RCT revealed that all muscles
      tested increased significantly after training. In the follow-up phase, the
      muscles of TC increased further (in TS decreased), but not all of them
      significantly (M. triceps brachii: p=0.017; M. biceps brachii: n.s.; M.
      latissimus dorsi: n.s.; M. rectus abdominis: p=0.002; M. biceps femoris right:
      n.s.; left: p=0.028; M. quadriceps femoris both n.s. = not sig.). Subjective
      performance showed no clear changes in the follow-up phase.This is the first
      study evaluating a follow-up phase of programmed sports therapy (PST) in PwH. PST
      (6-month) resulted in some PwH continuing the successful training. Benefits were
      training routine, safety and partially further positive training effects, e.g. in
      strength performance.

PMID- 29582921
TI  - The role of ultralarge multimers in recombinant human von Willebrand factor - a
      review of physico-and biochemical studies and findings in in vivo models and in
      humans with von Willebrand disease.
AB  - Ultralarge multimers (ULM) of VWF are considered to be the most active with
      respect to binding to platelets and to subendothelial structures and therefore
      are of critical importance for the function of VWF in stabilizing the primary
      hemostatic plug. In contrast to plasma-derived FVIII-VWF concentrates, human rVWF
      obtained from mammalian cell culture retains the full-spectrum of intact
      multimers, including ULM, as physiologically formed in the Golgi apparatus and
      stored in platelet alpha-granules and endothelial cell Weibel-Palade bodies. In
      the course of physico and biochemical, functional and animal studies, rVWF
      exhibited superiority in structure and function compared to pdVWF. These effects
      seemed to correlate with the multimer size and therefore might be attributed to
      the presence of ULM in rVWF preparations. The pharmacokinetic (PK), safety and
      efficacy characteristics seen in preclinical studies were further demonstrated in
      clinical trials.

PMID- 29582922
TI  - A rare case of unprovoked venous thromboembolism manifestation in a young patient
      with antithrombin Type IIB deficiency combined with inferior vena cava anomaly
      from Lithuania.
AB  - : Hereditary antithrombin (AT) deficiency is an autosomal-dominant disorder
      predisposing to venous and arterial thrombosis. Homozygosity resulting in severe
      AT deficiency is not compatible with life, apart from homozygous mutations
      affecting the heparin-binding site representing the most severe thrombophilia.
      PATIENTS AND METHODS: A 12-year-old previously healthy boy of Romani origin
      presented with a swollen, painful left leg and fever. Imaging revealed signs of
      inferior vena cava (IVC) thrombosis, the presence of interrupted intrahepatic IVC
      with azygos continuation and bilateral iliofemoral thrombosis with enlargement of
      the azygous and hemiazygos venous system. In addition, right pleural effusion and
      signs of bilateral renal pericortical cysts, possibly caused by retroperitoneal
      lymphangiectasia, were disclosed. Thrombophilia screening involving protein C,
      Protein S, Antithrombin (chromogenic assays based on the inhibition of FIIa and
      FXa, antigen concentration), APC resistance, prothrombin mutation and Lupus
      anticoagulants was performed using standard laboratory methods. Genetic analysis
      of the SERPINC1 gene was done by direct sequencing. RESULTS: Thrombophilia
      screening showed isolated decreased AT activity at 21% (RR 80-120%). AT levels
      were retested and remained decreased (33-36%) on two consecutive occasions.
      SERPINC1 gene analysis revealed a previously described homozygous mutation
      (Budapest III) causing type IIB deficiency (c.391C>T; p.Leu131Phe). A family
      study confirmed the same mutation in both parents and three siblings. The patient
      improved significantly following warfarin therapy and over the past 2.5 years did
      not experience new thromboembolism. CONCLUSIONS: This case represents a rare
      combination of two risk factors provoking manifestation of spontaneous venous
      thromboembolism at a young age requiring permanent anticoagulant therapy.

PMID- 29582923
TI  - [Rapid Report Hemophilia - Evidence in treatment of hemophilia from the IQWiG's
      perspective].
AB  - : The German Institute for Quality and Efficiency in Health Care (IQWiG)
      conducted a rapid report to assess the therapy of hemophilia patients. Based on a
      systematic literature search the IQWiG identified 16 studies which show that
      there is now sufficient information regarding questions that previously lacked
      data. A benefit assessment of prophylactic and on-demand-treatment concerning
      different treatment outcomes shows the superiority of the prophylactic therapy
      regarding major bleedings for all age groups. For the group of youths and adults
      the analysis shows additional benefits concerning health status and pain within
      the preceding four weeks. The alignment of guidelines with the identified
      evidence shows minor correspondence between the guidelines' references and
      included studies. However, the guidelines' statements primarily correspond with
      the results of the conducted benefit assessment. CONCLUSION: The IQWiG's rapid
      report shows prophylactic therapy to be superior to on-demand therapy. These
      findings represent a clear indication for attending physicians and payers for
      prophylaxis in patients with severe hemophilia A.

PMID- 29582925
TI  - Non-factor replacement therapies in hemophilia.

PMID- 29582924
TI  - Update: Direct oral anticoagulants (DOAC) - their use and clinical management
      remain a challenge.

PMID- 29582926
TI  - ?

PMID- 29582927
TI  - Direct oral anticoagulants for the treatment of cancer-associated venous
      thromboembolism.
AB  - Cancer patients with venous thromboembolism (VTE) are at increased risk for both
      bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin
      (LMWH) is the standard of care during the initial and longterm treatment phase
      (i.e. during the first 3 - 6 months of therapy) based on its overall beneficial
      safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct
      oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are
      approved for the treatment of acute VTE, and the combined six phase-3 trials have
      included > 1500 patients with active cancer, as defined by variable selection
      criteria. Subgroup analyses of these patients, either pooled or separately
      reported, suggest that DOACs could be a safe and efficacious alternative to VKA
      therapy for the treatment of cancer-associated VTE. However, the populations of
      cancer patients included in the DOAC and LMWH trials are not comparable with
      regard to mortality and VTE risk, and no specific data from direct head-to-head
      comparisons of DOACs with LMWHs are currently available. The use of DOACs for the
      management of VTE in cancer is thus not recommended by clinical practice
      guidelines.

PMID- 29582928
TI  - Direct oral anticoagulants (DOAC) - Management of emergency situations.
AB  - The worldwide increase in the aging population and the associated increase in the
      prevalence of atrial fibrillation and venous thromboembolism as well as the
      widespread use of direct oral anticoagulants (DOAC) have resulted in an increase
      of the need for the management of bleeding complications and emergency operations
      in frail, elderly patients, in clinical practice. When severe bleeding occurs,
      general assessment should include evaluation of the bleeding site, onset and
      severity of bleeding, renal function, and concurrent medications with focus on
      anti-platelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last
      intake of the DOAC and its residual concentration are also relevant. The site of
      bleeding should be immediately localized, anticoagulation should be interrupted,
      and local measures to stop bleeding should be taken. In life-threatening bleeding
      or emergency operations immediate reversal of the antithrombotic effect may be
      indicated. If relevant residual DOAC-concentrations are expected and surgery
      cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific
      antidote should be given. While idarucizumab, the specific antidote for
      dabigatran, has been recently approved for clinical use, the recombinant factor X
      protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation
      factor Xa, and ciraparantag, a universal antidote, are not available. Future
      cohort studies are necessary to assess the efficacy and safety of specific and
      unspecific reversal agents in "real-life" conditions. This was the rationale for
      introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated
      with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non
      interventional registry, which will evaluate the effects of specific and
      unspecific reversal agents in patients with life-threatening bleeding or
      emergency operations either treated with DOACs or vitamin K antagonists.

PMID- 29582929
TI  - Update on Direct Oral AntiCoagulants (DOACs).
AB  - Recent findings require an update of previous recommendations for the
      perioperative use of Direct Oral AntiCoagulants (DOACs). A break in preoperative
      treatment of 24-96 hours is recommended based on the pharmacokinetic profiles of
      DOACs and depends on individual patient characteristics, their renal and possibly
      liver function, and their surgery-related risk of bleeding. In cases of renal or
      hepatic insufficiency, whether to extend the preoperative interruption of IIa-
      and Xa-inhibitors is a clinical decision that must be reached on an individual
      patient basis. In cases of epidural or spinal anaesthesia, more conservative
      pausing-intervals are recommended due to the risk of persistent neurologic
      deficits (e.g., paraplegia) following the development of spinal subdural and
      epidural haematomas. Elective surgery should be postponed according to these
      recommendations. Preoperative "bridging" with LMWH (more precisely referred to as
      "switching") should be omitted due to a significantly increased risk of bleeding.
      In addition, the incidence of perioperative thromboembolic risks, such as DVT,
      PE, and stroke, are no different whether interruption or "switching" is
      undertaken. Postoperatively, the DOACs can be reinstituted within the first 24
      hours. In cases of major surgery or if there is a higher risk of bleeding,
      resumption of DOACS should only begin after 24-72 hours. In patients with an
      elevated thromboembolic risk, transient postoperative LMWH administration can be
      recommended during this period.Interaction of DOACs with other drugs usually
      occurs during the absorption, transport and elimination of these drugs.
      Therefore, substance- specific restrictions and recommendations should be
      observed during these times. In everyday clinical practice, webbased, independent
      information portals on drug-interactions are very helpful in providing safe and
      rapid information about potential interactions when DOACs are used in combination
      with other drugs, especially during perioperative management.Non-adherence to
      medications is a worldwide problem that has dangerous and costly consequences.
      Present data suggest that persistence is the primary factor that supports
      adherence. Despite the adherence data presented in the DOACS approval studies
      (e.g., persistence in the treatment of acute venous thromboembolism has been
      reported to be between 94-99%), the first registries and meta-analyses provide
      sobering results regarding the incidence of persistence and the success rate of
      interventions designed to improve adherence with DOACs in cases of long-term
      usage.

PMID- 29582930
TI  - DOAC use in patients with chronic kidney disease.
AB  - Direct oral anticoagulants (DOACs) are increasingly prescribed substances in
      patients with indication for effective anticoagulation. Patients with chronic
      kidney disease (CKD) have a high burden of cardiovascular risk and are more
      likely to develop atrial fibrillation (AF) than patients without CKD. Patients
      with mild to moderate CKD benefit from DOACs, especially when having intolerance
      to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients
      with rare renal disease and hypercoagulabilic state. DOACs are to a large extent
      eliminated by renal excretion. Since prospective randomised data in CKD patients
      are sparse, the decision for anticoagulative therapy is challenging especially in
      patients with severe renal impairment. The direct factor Xa-inhibitors are
      approved for use even in patients with an estimated glomerular filtration rate
      (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a
      regular basis is essential before initiation and after start of DOAC, especially
      for patients at risk for acute renal failure (elderly, diabetics, patients with
      preexisting kidney disease). None of the DOACs is approved in CKD patients with
      end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not
      recommended for kidney transplant patients under immunosuppression with
      calcineurin inhibitors. In these patients conventional therapy with VKA is the
      only option, which has to be monitored closely since it has potential adverse
      effects.

PMID- 29582931
TI  - Thromboembolic Risks of Non-Factor Replacement Therapies in Hemophilia.

PMID- 29582932
TI  - Development and Usability of a Smartphone Application for Tracking Antiretroviral
      Medication Refill Data for Human Immunodeficiency Virus.
AB  - BACKGROUND: Adherence to antiretroviral medication leads to HIV suppression and
      decreased morbidity and mortality. In resource- limited settings, the dependence
      on paper medical charts and unstable electronic health records creates a
      challenge to monitoring medication adherence. A pharmacy-based strategy that
      utilizes existing cellular phone infrastructure may lead to a more stable system
      to monitor adherence. OBJECTIVES: To develop and evaluate the usability of a
      smartphone-based software application (app) for tracking antiretroviral
      medication refill data in a resource-limited setting. METHODS: A pharmacy-based
      smartphone app for tracking HIV medication adherence was developed through a
      multi-step rapid prototyping process. The usability of the app was assessed
      during the daily activities of pharmacy dispensers at HIV clinics in and around
      Gaborone, Botswana using a validated computer usability survey. RESULTS: The
      study demonstrated the effective development of and favorable end-user responses
      to a pharmacy-based HIV medication adherence app. End users had suggestions for
      minor changes to improve the app's functionality. CONCLUSIONS: In resource
      limited settings where electronic health record support is limited, such a system
      was feasible and appealing. In the future, this system may allow for improved HIV
      medication adherence tracking and be applied to medications beyond
      antiretrovirals.

PMID- 29582934
TI  - Mining Major Transitions of Chronic Conditions in Patients with Multiple Chronic
      Conditions.
AB  - OBJECTIVES: Evolution of multiple chronic conditions (MCC) follows a complex
      stochastic process, influenced by several factors including the inter
      relationship of existing conditions, and patient-level risk factors. Nearly 20%
      of citizens aged 18 years and older are burdened with two or more (multiple)
      chronic conditions (MCC). Treatment for people living with MCC currently accounts
      for an estimated 66% of the Nation's healthcare costs. However, it is still not
      known precisely how MCC emerge and accumulate among individuals or in the general
      population. This study investigates major patterns of MCC transitions in a
      diverse population of patients and identifies the risk factors affecting the
      transition process. METHODS: A Latent regression Markov clustering (LRMCL)
      algorithm is proposed to identify major transitions of four MCC that include
      hypertension (HTN), depression, Post- Traumatic Stress Disorder (PTSD), and back
      pain. A cohort of 601,805 individuals randomly selected from the population of
      Iraq and Afghanistan war Veterans (IAVs) who received VA care during three or
      more years between 2002-2015, is used for training the proposed LRMCL algorithm.
      RESULTS: Two major clusters of MCC transition patterns with 78% and 22%
      probability of membership respectively were identified. The primary cluster
      demonstrated the possibility of improvement when the number of MCC is small and
      an increase in probability of MCC accumulation as the number of co- morbidities
      increased. The second cluster showed stability (no change) of MCC overtime as the
      major pattern. Age was the most significant risk factor associated with the most
      probable cluster for each IAV. CONCLUSIONS: These findings suggest that our
      proposed LRMCL algorithm can be used to describe and understand MCC transitions,
      which may ultimately allow healthcare systems to support optimal clinical
      decision- making. This method will be used to describe a broader range of MCC
      transitions in this and non-VA populations, and will add treatment information to
      see if models including treatments and MCC emergence can be used to support
      clinical decision-making in patient care.

PMID- 29582935
TI  - The Charlson Comorbidity Index in Registry-based Research.
AB  - BACKGROUND: Comorbidities may have an important impact on survival, and
      comorbidity scores are often implemented in studies assessing prognosis. The
      Charlson Comorbidity index is most widely used, yet several adaptations have been
      published, all using slightly different conversions of the International
      Classification of Diseases (ICD) coding. OBJECTIVE: To evaluate which coding
      should be used to assess and quantify comorbidity for the Charlson Comorbidity
      Index for registry-based research, in particular if older ICD versions will be
      used. METHODS: A systematic literature search was used to identify adaptations
      and modifications of the ICD-coding of the Charlson Comorbidity Index for general
      purpose in adults, published in English. Back-translation to ICD version 8 and
      version 9 was conducted by means of the ICD-code converter of Statistics Sweden.
      RESULTS: In total, 16 studies were identified reporting ICD-adaptations of the
      Charlson Comorbidity Index. The Royal College of Surgeons in the United Kingdom
      combined 5 versions into an adapted and updated version which appeared
      appropriate for research purposes. Their ICD-10 codes were back-translated into
      ICD-9 and ICD-8 according to their proposed adaptations, and verified with
      previous versions of the Charlson Comorbidity Index. CONCLUSION: Many versions of
      the Charlson Comorbidity Index are used in parallel, so clear reporting of the
      version, exact ICD- coding and weighting is necessary to obtain transparency and
      reproducibility in research. Yet, the version of the Royal College of Surgeons is
      up-to-date and easy-to-use, and therefore an acceptable co-morbidity score to be
      used in registry-based research especially for surgical patients.

PMID- 29582936
TI  - Addressing the Data Linking Challenges.
AB  - BACKGROUND: PARENT JA (cross-border Patient Registries iNiTiative Joint Action),
      a joint EU and Member States project, has conducted a research among EU patient
      registries aimed at gathering information on the registries' interoperability
      readiness. Leaning on the information and data collected through the previous
      PARENT JA research, this study aims to provide more detailed view into the
      registry holders' practical challenges with data linking. Since the studies which
      dealt with patient data exchange have often neglected the registry holders'
      performance of data exchange, we wanted to put a spotlight on various EU registry
      holders' practices and operations, aiming to detect their needs and concerns in
      the process of running an interoperable registry. The focus of this study was
      identifying the main practices and challenges in patient registries
      interoperability improvement. METHODS: The basis for this analysis were the data
      collected in the series of structured interviews. The size of the interview
      sample was 13 patient registries, each from a different EU country. The
      structured interview consisted of nine questions and was conducted in two parts:
      oral and written. The answers were analysed using open coding. RESULTS: Results
      are interpreted in the context of the six main themes that emerged through a
      comprehensive analysis. (1) Examples of data exchange: The most common reported
      data exchange practices were seen only as a way to achieve the most immediate
      needs and interests of the individual registries. (2) Awareness and use of
      international standards: International data and clinical standards were not
      widely used by the interviewed registries. (3) Use of data models and formats: In
      the area of data models and formats there is no universally used practice. (4)
      Data request protocols and procedures: Procedures and protocols varied, mostly
      depending on the national legal systems in which the patient registries operated.
      (5) Data security and integrity: Security of personal data was a universal
      concern for all registry holders that were interviewed; identifiable individual
      data was shared only in one case. (6) Opportunities and challenges of registry
      interoperability: most registry holders responded that their registries were well
      prepared for interoperability practices and that data exchange has never been
      their primary operative concern. CONCLUSIONS: Most of the difficulties regarding
      data linking were not necessarily associated with technical issues, which
      registry holders listed outright. Our analysis showed that the lack of
      interoperability came as a result of organizational or legal constraints that
      made the registries unable to process and conduct data linking quickly and
      effectively with other sources.

PMID- 29582937
TI  - Update: S1-Leitlinie Myokard-Perfusions-SPECT.

PMID- 29582938
TI  - [Taste dysfunction (dysgeusia) and radioiodine therapy of thyroid cancer - Be
      aware of side effects by antidepressants and sedatives].
AB  - In addition to xerostomia, taste dysfunction (hypo-, dysgeusia) is an independent
      side effect of radioiodine therapy of thyroid cancer. Hypogeusia results from
      damage of the small mucous salivary glands in the vicinity of the taste buds.
      Particularly in those patients, who are treated with drugs such as
      antidepressants or sedatives, taste dysfunction becomes frequently clinically
      symptomatic. If feasible, therapy regimens bearing a potential risk for taste
      dysfunction should be switched. Additional damage to taste function should be
      minimalized, including cessation of smoking, change of agents for dental hygiene,
      and change of toothpaste. If the medical indication for ablative radioiodine
      therapy is based on the patient's decision, the patient should be informed about
      alternative strategies. Potential clinical consequences of the sialadenitis
      (xerostomia, alter ation in taste, risk of caries and tooth extraction, lacrimal
      gland dysfunction, tearing and need of dacryocystorhinostomy) should be revealed
      completely. Adapted to the initial risk of relapse, the131 I-activity for
      ablation should be reduced to the latest standard of care. Clinical data are
      currently too heterogeneous to decide whether rhTSH might reduce the rate of
      dysgeusia. The specialist in nuclear medicine should be aware of the
      multifactorial causes of taste dysfunction, in particular if the patient seeks
      medical advice after radioiodine therapy.

PMID- 29582940
TI  - Closed-system drug-transfer devices plus safe handling of hazardous drugs versus
      safe handling alone for reducing exposure to infusional hazardous drugs in
      healthcare staff.
AB  - BACKGROUND: Occupational exposure to hazardous drugs can decrease fertility and
      result in miscarriages, stillbirths, and cancers in healthcare staff. Several
      recommended practices aim to reduce this exposure, including protective clothing,
      gloves, and biological safety cabinets ('safe handling'). There is significant
      uncertainty as to whether using closed-system drug-transfer devices (CSTD) in
      addition to safe handling decreases the contamination and risk of staff exposure
      to infusional hazardous drugs compared to safe handling alone. OBJECTIVES: To
      assess the effects of closed-system drug-transfer of infusional hazardous drugs
      plus safe handling versus safe handling alone for reducing staff exposure to
      infusional hazardous drugs and risk of staff contamination. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation
      databases, the World Health Organization International Clinical Trials Registry
      Platform, and ClinicalTrials.gov to October 2017. SELECTION CRITERIA: We included
      comparative studies of any study design (irrespective of language, blinding, or
      publication status) that compared CSTD plus safe handling versus safe handling
      alone for infusional hazardous drugs. DATA COLLECTION AND ANALYSIS: Two review
      authors independently identified trials and extracted data. We calculated the
      risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using
      both fixed-effect and random-effects models. We assessed risk of bias according
      to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool,
      used an intracluster correlation coefficient of 0.10, and we assessed the quality
      of the evidence using GRADE. MAIN RESULTS: We included 23 observational cluster
      studies (358 hospitals) in this review. We did not find any randomised controlled
      trials or formal economic evaluations. In 21 studies, the people who used the
      intervention (CSTD plus safe handling) and control (safe handling alone) were
      pharmacists or pharmacy technicians; in the other two studies, the people who
      used the intervention and control were nurses, pharmacists, or pharmacy
      technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor
      (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5
      studies), and not stated (2 studies). The studies' descriptions of the control
      groups were varied. Twenty-one studies provide data on one or more outcomes for
      this systematic review. All the studies are at serious risk of bias. The quality
      of evidence is very low for all the outcomes.There is no evidence of differences
      in the proportion of people with positive urine tests for exposure between the
      CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52;
      I2 = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control:
      91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1
      hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and
      cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1
      hospital; 36 participants; 0% in both groups).There is no evidence of a
      difference in the proportion of surface samples contaminated in the pharmacy
      areas or patient-care areas for any of the drugs except 5-fluorouracil, which was
      lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3
      studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).The amount
      of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the
      control group (MD -49.34 pg/cm2, 95% CI -84.11 to -14.56, I2 = 0%, 7 studies; 282
      hospitals, 1793 surface samples). Additionally, one interrupted time-series study
      (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD
      and CSTD (3.9439 pg/cm2, 95% CI 1.2303 to 6.6576; P = 0.010), but not between
      CSTD and post-CSTD withdrawal (-1.9331 pg/cm2, 95% CI -5.1260 to 1.2598; P =
      0.20). There is no evidence of difference in the amount of the other drugs
      between CSTD and control groups in the pharmacy areas or patient-care areas.None
      of the studies report on atmospheric contamination, blood tests, or other
      measures of exposure to infusional hazardous drugs such as urine mutagenicity,
      chromosomal aberrations, sister chromatid exchanges, or micronuclei
      induction.None of the studies report short-term health benefits such as reduction
      in skin rashes, medium-term reproductive health benefits such as fertility and
      parity, or long-term health benefits related to the development of any type of
      cancer or adverse events.Five studies (six hospitals) report the potential cost
      savings through the use of CSTD. The studies used different methods of
      calculating the costs, and the results were not reported in a format that could
      be pooled via meta-analysis. There is significant variability between the studies
      in terms of whether CSTD resulted in cost savings (the point estimates of the
      average potential cost savings ranged from (2017) USD -642,656 to (2017) USD
      221,818). AUTHORS' CONCLUSIONS: There is currently no evidence to support or
      refute the routine use of closed-system drug transfer devices in addition to safe
      handling of infusional hazardous drugs, as there is no evidence of differences in
      exposure or financial benefits between CSTD plus safe handling versus safe
      handling alone (very low-quality evidence). None of the studies report health
      benefits.Well-designed multicentre randomised controlled trials may be feasible
      depending upon the proportion of people with exposure. The next best study design
      is interrupted time-series. This design is likely to provide a better estimate
      than uncontrolled before-after studies or cross-sectional studies. Future studies
      may involve other alternate ways of reducing exposure in addition to safe
      handling as one intervention group in a multi-arm parallel design or factorial
      design trial. Future studies should have designs that decrease the risk of bias
      and enable measurement of direct health benefits in addition to exposure. Studies
      using exposure should be tested for a relevant selection of hazardous drugs used
      in the hospital to provide an estimate of the exposure and health benefits of
      using CSTD. Steps should be undertaken to ensure that there are no other
      differences between CSTD and control groups, so that one can obtain a reasonable
      estimate of the health benefits of using CSTD.

PMID- 29582941
TI  - [THE NEW HADASSAH-HEBREW UNIVERSITY MEDICAL CENTER: A LEADER IN ISRAELI PUBLIC
      MEDICINE].
AB  - INTRODUCTION: Hadassah-Hebrew University Medical Center is regaining its lead in
      Israeli public medicine with clinical excellence, state-of-the art technology,
      high achievement in research, and outstanding medical education for students and
      trainees. Hadassah has two campuses at Ein Kerem and Mount Scopus that together
      offer 1200-hospital beds and 40 hybrid and advanced operating rooms. Hadassah
      Medical Center, an initiative of Hadassah organization led by Henrietta Szold, is
      one of the foremost health care providers in Israel. Together, the Hebrew
      University and Hadassah are home to Schools of Medicine, Pharmacy, Nursing,
      Public Health, Occupational Therapy, and Dental Medicine. The medical school
      enrolls over 1000 medical students including a special track for military
      physicians. Hadassah opened the new Davidson medical tower in 2012 and the
      development of new infrastructure continues for Centers of Excellence in Surgery,
      Oncology, Hematology, and Medicine, for the benefit of the public in greater
      Jerusalem and all of Israel. In this journal, we will present 12 articles that
      represent the integration of state-of-the-art clinical medicine and research
      technologies, all dedicated to advancing medicine for the people of Israel.

PMID- 29582942
TI  - [FLUOROSCOPIC BASED NAVIGATION IN ORTHOPAEDIC TRAUMA - A REVIEW OF A LARGE
      CENTER'S EXPERIENCE].
AB  - INTRODUCTION: Computer Assisted Orthopaedic Surgery (CAOS) was introduced in the
      late 1990's and early 2000's. Since then its application in orthopaedic trauma
      has been utilized mainly as augmented fluoroscopy for intraoperative navigation.
      From 2010 our center implemented an advanced system allowing further expansion of
      this technology. AIMS: The aim of this study was to describe the experience with
      an advanced fluoroscopic based CAOS system in our center. METHODS: The BrainLabTM
      Trauma 3.0 utilizes a handheld fluoroscope tracker, enables tracking of two
      anatomical objects and intraoperative planning. We implemented this system for
      the performance of 126 navigated procedures between the years 2011-2014. The
      procedures included 58 cases of navigated hip fracture pinning, 9 plate
      navigation for distal femoral fractures, 19 iliosacral screw insertions, 20
      femoral fracture reductions, and 12 other procedures (acetabular screws,
      osteotomies etc). RESULTS: The mean age of patients was 52 years (range 16-82
      years); 46 male and 80 female patients. The mean operating room time was 157
      minutes (range 70 to 470 minutes). The average radiation required was 550 rad cm2
      (~30 sec fluoroscopic time). Overall estimated additional OR time was estimated
      as 10-15 minutes for hip pinning, 15-20 minutes for pelvic iliosacral screws and
      30-45 minutes of additional OR time for femur fracture reduction for length and
      rotation. In 5% of cases (6 patients), navigation was aborted due to technical
      reasons. No misplaced hardware due to the use of navigation was documented.
      CONCLUSIONS: CAOS is a powerful tool in trauma surgery with 95% success rate,
      with a reasonable added burden time. Although 3D navigation may be more useful in
      the pelvis, even two-dimensional navigation increases precision and implant
      placement. Femoral fracture reduction for accurate length and rotation control is
      solely enabled by CAOS. In the future, more time efficient and user-friendly
      systems will enable widespread use of these technologies in orthopaedic trauma.

PMID- 29582943
TI  - [ADVANCES IN THE TREATMENT OF RETINOBLASTOMA AT HADASSAH IN THE LAST THREE
      DECADES].
AB  - INTRODUCTION: Retinoblastoma (RB) is a malignant tumor presenting in the eyes of
      infants and children, which endangers life, the eye and vision. The treatment of
      RB has undergone marked changes in recent years, and great progress has been made
      in our ability to preserve eyes. Over the last three decades most Israeli
      patients with RB have been treated in the National Specialty Ocular Oncology
      Service at the Hadassah-Hebrew University Medical Center in Jerusalem. AIMS: To
      describe advances in the primary treatment of RB with an emphasis on eye
      preserving treatments. METHODS: The study included a retrospective cohort of
      patients who were diagnosed and treated at our center over the last three
      decades. Review of patients' records was approved by the Hadassah IRB. RESULTS:
      From 1988 to 2014 we diagnosed 290 children (138 girls - 47.6%). The mean age at
      diagnosis (+/-SE) was 18.1+/-1.2 months, median 12.5 months. RB was unilateral in
      55.6% of the cases, bilateral in 41.3% and unilateral multifocal in 3.1%. There
      was an even distribution of disease severity (IRB grouping). Since the advent of
      IV chemotherapy (IVC) there has been a decrease in the rate of eye enucleation
      from ~90% to ~30% of the children until the year 2000 with a stable rate
      thereafter. In the years 1990-2000 there was an increase followed by a decrease
      in the use of primary external beam radiotherapy (EBRT), and a parallel small
      increase in the use of brachytherapy from the mid '90s until today. The recently
      introduced novel treatments - intravitreal (IVitC) and intra-arterial
      chemotherapy (IAC) - were used as a complimentary treatment to IVC, and not yet
      as a single primary modality until 2014. CONCLUSIONS: IVC replaced the need to
      enucleate in most of the cases, but 30% of children still require a primary
      enucleation. DISCUSSION: IVC usually requires additive treatments (thermal
      cryotherapy, trans-pupillary thermotherapy - TTT, brachytherapy and/or local
      chemotherapy - IVitC and IAC) and with the use of multi-modal therapy many eyes
      can be preserved. In the period reported in the current manuscript, the use of
      IAC as a primary treatment approach was only used in isolated cases. In Summary,
      There have been significant advances in our ability to save eyes, and the field
      continues to progress.

PMID- 29582944
TI  - [PERCUTANEOUS TREATMENT OF SMALL RENAL TUMORS BY THERMAL ABLATION].
AB  - INTRODUCTION: Kidney cancer accounts for approximately 2-3 % of all types of
      cancers. Renal tumors prevalence and especially the prevalence of small renal
      tumors, is on the rise. About half of the tumors currently diagnosed are smaller
      than 4 cm. Minimally invasive methods of radiofrequency ablation technology were
      recently developed for the treatment of small renal tumors and are characterized
      by reducing the surgical and anesthetic risk. The ablation is performed with a
      percutaneous approach guided by ultrasound, CT or MRI. We reviewed the results of
      this treatment. METHODS: A total of 75 patients with a mean age of 69.5 years (27
      - 90) were treated using RF during the period 2007-2014. The average tumor
      diameter was 28.4 mm (11-58 mm); 40 tumors were exophytic and 30 were central.
      Monitoring protocol after treatment included imaging after 1, 3, 6, 12 months
      subsequent to treatment and later annually; median follow-up time was 21 months
      (1 - 97). RESULTS: Evidence of tumor recurrence was observed in 9 patients
      (11.4%); 8 were treated successfully by another RF session. Cases in which
      recurrence was observed were characterized by a tumor larger than 30 mm (5/9) and
      adjacent to renal cysts (3/9); 5 of the lesions were central (endophytic)
      (P=0.5). One patient died due to metastatic RCC and a metastatic disease
      developed in two additional patients who died of other causes. CONCLUSIONS: It is
      possible to destroy most of the small renal tumors by RF ablation. When the tumor
      size is up to 30 mm, a 94% long-term cure may be reached. In the event of renewed
      growth of the tumor, the treatment can be repeated with good results. In light of
      short-term experience, it is recommended to limit this treatment to older
      patients, with a short life expectancy or when anesthetic risks prohibit surgery.

PMID- 29582945
TI  - [SPONTANEOUS PARENCHYMAL INTRACRANIAL HEMORRHAGE - A DIAGNOSTIC CHALLENGE].
AB  - INTRODUCTION: Non-traumatic intracranial hemorrhage (ICH) is a devastating event
      associated with a high rate of morbidity and mortality. Patient age, hemorrhage
      location, number of foci, and underlying diseases are important clues to the
      etiology. Non-contrast head CT, given its availability and high sensitivity in
      detecting blood products, is frequently the first tool to readily detect ICH;
      however, different types of hemorrhages may share a common appearance on CT and
      the optimal therapeutic approach varies depending on etiology. An additional
      diagnostic work-up is frequently indicated to make the final diagnosis and to
      assist in urgent patient management. CT- and MR angiography, and digital
      angiography can diagnose vascular anomalies, CT venography can reveal cerebral
      vein thrombosis, diffusion-weighted MRI (DWI) may show hemorrhagic transformation
      of an infarct, and susceptibility-weighted MRI (SWI) may detect hypertensive and
      amyloid angiopathy-related microbleeds. MR also has a major role in revealing
      underlying etiologies such as cavernoma, primary brain tumor or metastases. These
      imaging tools assist in determining the cause of ICH, and also in assessing the
      risk of deterioration. Prognostic factors such as size, location, mass effect,
      and detection of the "spot sign" all play an important role in foreseeing
      possible deterioration, thus allowing prompt intervention. This study will
      present cases of intraparenchymal hemorrhage from different etiologies in
      patients who presented to the Hadassah-Hebrew University Medical Center, with the
      goal of illustrating the role of imaging in patient management and decision
      making.

PMID- 29582946
TI  - [EFFECTS OF CANNABIS EXTRACT PREMEDICATION ON ANESTHETIC DEPTH].
AB  - BACKGROUND: Cannabis is the most widely used illicit drug in the world, used by
      approximately 2.7-4.9% of the world's population, and 7.6-10.2% of Israel's
      adults. During the past few years, legal systems around the world have enacted
      large scale adoption of the legalization of both medical and recreational
      cannabis. Anesthetists should therefore be prepared to treat patients who used
      cannabis and are undergoing elective or emergency operations. However, the
      interactions between cannabinoids and general anesthetic agents and the possible
      implications for patient care are not yet fully understood. OBJECTIVES: The study
      aimed to examine how preoperative use of cannabis affects the anesthesia process,
      and whether this use requires special attention by the anesthesiologists during
      surgery. Hence, we examined the effect of preoperative administration of cannabis
      extract Sativex (nabiximols) on obtained BIS value relative to the concentration
      of anesthetic gases. METHODS: This study is a double-blind randomized controlled
      trial. Twenty-seven patients undergoing elective orthopedic surgery under general
      anesthesia were randomly allocated to one of the following regimes: high dose
      cannabis (6), low dose cannabis (8), active placebo (6) and placebo (7). The
      study drugs were administered as premedication 20 minutes before induction of
      general anesthesia in a double-blind fashion. Cannabis was administered in the
      form of nabiximols (Sativex(r)), which is a highly-standardized extract of
      cannabis plants containing known drug dosages. During the surgery, hemodynamic
      parameters were monitored, and the anesthesia depth was measured using a BIS
      monitor, which is based on brain activity analysis. RESULTS: We found a
      significant effect of treatment groups on bispectral index (BIS) after
      controlling for minimum alveolar concentration (MAC). The average BIS values, as
      measured during steady state anesthesia, were significantly higher in the high
      dose cannabis treatment group. CONCLUSIONS: This study provides the first
      evidence that cannabinoids may affect the BIS. We speculate that the cannabinoid
      induced increase in BIS may be the result of changes in EEG activity rather than
      an indication of a shallower anesthetic state. However, this hypothesis should be
      examined in further studies. The clinical importance of this study is that with
      patients who use cannabis adjacent to general anesthesia induction, one cannot
      rely on the BIS monitoring for the purpose of determining the patient sedative
      state.

PMID- 29582947
TI  - [LONG TERM FOLLOW-UP OF TRANSCATHETER SELF EXPANDABLE AORTIC VALVE IMPLANTATION].
AB  - INTRODUCTION: Aortic stenosis is the most common significant valvular disease in
      the western world. These patients are treated operatively unless they are at high
      operative risk or inoperable. During the last decade an alternative approach has
      evolved - transcatheter aortic valve implantation (TAVI). This method was shown
      to be at least as effective and safe as the operative one. However, very little
      data exists on long term follow-up (5 years and above), especially regarding
      valve durability and patient survival. OBJECTIVES: To present a long term follow
      up on patients who underwent transcutaneous self-expandable aortic valve
      implantation in our department between the years 2008-2011. METHODS: In September
      2008 the first CoreValve implantation was performed in Israel at Hadassah Medical
      Center. All records of patients who were transplanted between 9.2008 and 10.2011
      were reviewed. The function of the valve early after the procedure was compared
      to its function at the end of the follow-up period. RESULTS: A total of 38
      patients (out of 71) survived at least 54 months, of them, 19 have an
      echocardiography examination at the end of the follow-up period. In all patients
      the implanted valve was found to function well at the end of the follow-up
      period, without significant stenosis or paravalvular leak. In fact, in
      approximately half of these patients, the degree of paravalvular leak decreased
      during the follow-up period. DISCUSSION: On long term (5 years) follow-up of
      patients who were implanted with the self-expandable aortic valve (CoreValve), no
      deterioration of the valve was observed. In fact, in approximately half of the
      patients, a decrease in the severity of the paravalvular leak was demonstrated.

PMID- 29582948
TI  - [ADVANCES IN FETAL THERAPY IN COMPLICATED MONOCHORIONIC PREGNANCIES AND IN SEVERE
      CONGENITAL DIAPHRAGMATIC HERNIA: FIVE YEARS EXPERIENCE].
AB  - INTRODUCTION: : Minimally invasive fetal therapeutic procedures reduce the
      morbidity and mortality in monochorionic (MC) twins and in fetuses with
      congenital diaphragmatic hernia (CDH). MC pregnancies share their blood systems
      due to communicating vessels over their single placenta and may develop specific
      complications: Twin-to-Twin transfusion syndrome (TTTS), Selective intrauterine
      growth restriction (sIUGR), Twin Anemia-Polycythemia Sequence (TAPS), Twin
      Reverse Arterial Perfusion Syndrome (TRAP) or anomalies in one. Half of
      complicated MC require intrauterine interventions. Severe CDH is linked to a high
      rate of neonatal death due to pulmonary hypoplasia. Fetoscopic tracheal occlusion
      (FETO) with a balloon improves postnatal outcome. AIMS: A fetal therapy center
      was established in the Hadassah Medical Centers, Jerusalem in 2011 for
      intrauterine interventions. We report our 5 years' experience. METHODS: This
      prospective cohort follows the outcome of MC pregnancies and cases of severe CDH
      which underwent therapeutic fetal procedures in Hadassah between the years 2011
      16. RESULTS: Out of 114 procedures, 95 were in MC: 84 monochorionic diamniotic
      twins, 7 monochorionic monoamniotic twins, 2 dichorionic triamniotic triplets and
      2 monochorionic triplets. We treated 65 TTTS cases with fetoscopy and laser
      ablation of communicating vessels. The survival rate of both twins was 58.5% and
      at least one survived in 81.5% of the cases. In 2nd/3rd trimesters selective
      termination of 15 cases the survival rate of the remaining twin was 87%. In 11
      cases of TRAP sequence treated with laser ablation of the feeding vessel the
      survival of the remaining twin was 91%. In 19 fetoscopies in severe CDH, 12 were
      for balloon insertion and 7 for removal. Endotracheal balloon was successfully
      placed in 11 of 12 cases (10 left-sided, 1 right-sided CDH). Balloon removal was
      prenatally performed by elective fetoscopy (n=7) or by intrapartum urgent
      puncture. There were no intrauterine fetal deaths. In isolated left-sided CDH the
      survival was 57%, whereas none survived in non-isolated left-sided CDH and right
      sided CDH. CONCLUSIONS: In-utero procedures are safe for the mother and increase
      newborn survival in MC pregnancies, thus specialized clinics are life-saving.
      FETO is a therapeutic option for severe CDH. Our results meet similar
      achievements reported by other leading world centers.

PMID- 29582949
TI  - [NEUROPSYCHIATRY AND COMPUTATIONAL MEDICINE].
AB  - INTRODUCTION: The classical model of medicine is based on, first, history taking,
      followed by physical examination, data analysis by the clinician and their
      further validation using biological tests. Based on this, the clinician may plan
      the medical treatment. In neuropsychiatry, this model is even more limited as
      physical examination is based mostly on a patient-doctor conversation, and
      biological or imaging tests are directed mostly to extract the structural basis
      for the clinical manifestations. The rapidly developing computational revolution
      have not yet significantly influenced this model. Nevertheless, various
      advancements in machine-learning, algorithms, computation, internet, hardware,
      sensors, image processing and more intend to change this process profoundly. In
      this article we will review this process of computational medicine and exemplify
      how it enables new approaches in the domains of pain and dementia.

PMID- 29582950
TI  - [HADASSAH MEDICAL ORGANIZATION - A PIONEER IN POPULATION HEALTH].
AB  - INTRODUCTION: Population health is a term encompassing "the health outcomes of a
      group of individuals, including the distribution of such outcomes within the
      group." Only recently have hospitals viewed themselves as focal points for
      promoting health in a community, involving themselves with population health.
      Hadassah Medical Organization (HMO), however, has been in the business of
      population health since its founding. Its early programs, promoting and
      delivering nutritional support, maternal-child health and other services to the
      Yishuv's inhabitants, showed that the HMO defined its community broadly. Hospital
      care came later. The HMO was established together with the Hebrew University
      Israel's first School of Public Health and Community Medicine in the 1960's,
      contributing >1200 Israeli alumni, and exposing thousands of medical students to
      population health. The School's founders developed Community-Oriented Primary
      Care, aimed at assessing and addressing health determinants and outcomes at the
      community level implemented in many centers worldwide. Reaching beyond Israel's
      borders, the School has trained a global public health workforce through its
      International Masters in Public Health with >820 graduates from 92 countries.
      HMO's researchers have made important contributions in the fields of
      epidemiology, health economics and policy and population health methodology as
      well as hospital and community quality of care. This article reviews HMO's
      contribution to population health at local, municipal, national and international
      levels. We will demonstrate the unique circumstances in Hadassah, Jerusalem and
      Israel which have enabled world-class research and training in population health,
      identifying important contributions to policy and service provision, as well as
      addressing future population health challenges.

PMID- 29582951
TI  - [FROM THE LAB BENCH TO THE PATIENT - CAN INJURED SKELETAL TISSUES REGENERATE?]
AB  - INTRODUCTION: Regenerative medicine research has evolved significantly in recent
      years. There is a great un-met clinical need for developing new treatments that
      will induce regeneration of injured skeletal tissues in cases such as large bony
      defects caused by trauma or tumor resection, articular cartilage defects and torn
      or degenerate tendons and ligaments. Except for bone that can regenerate small
      defects, all other skeletal tissues do not hold the natural capability for
      regeneration after injury and rather form a less functional scar tissue. In order
      to induce tissue regeneration, it is now believed that three crucial elements
      must reach the injured zone: a) multipotent cells that can rapidly proliferate
      and differentiate to form the injured tissues, such as mesenchymal stem cells for
      skeletal tissues; b) extra-cellular matrix that will support the newly built
      tissues, and c) the correct molecular signals. Using diverse research tools and
      expertise, our department focused its research on basic, translational and
      clinical solutions for injured and degenerative skeletal tissues. In this review
      we will describe our different research directions, from in-vitro cell cultures
      and animal models studies to human clinical trials.

PMID- 29582952
TI  - [EXOME ANALYSIS - A GAME CHANGER IN PEDIATRICS].
AB  - INTRODUCTION: Thirteen years after the completion of the human genome project,
      the determination of the genomic sequence of the coding parts of the DNA (the
      exones, hence the exome), has turned into a primary diagnostic tool in daily use
      in clinical practice. The Department of Genetics at Hadassah was the first in
      Israel to introduce exome analysis as a robust diagnostic tool into the pediatric
      departments. Till now 2600 exomes were analyzed at Hadassah, 850 of them in 2016
      alone. Exome analysis is cheap and fast, enabling precise and non-invasive
      diagnosis for a vast array of genetic disorders and congenital malformations. The
      unique composition of the population which the hospital serves (marked by a high
      rate of consanguinity) enabled reaching diagnosis in 65% of the cases, twice the
      rate in medical centers worldwide. The results of this analysis enable genetic
      counseling to patients' families and prevention of serious disorders. Moreover,
      the results contribute to the understanding of the biological basis of newly
      identified disorders and in certain cases assist in the management of the
      patients. The major limitation of exome analysis is the multitude of identified
      variants which exist in any individual and which challenge our ability to pick
      the disease-causing variant. In the case of a disease-causing variant in a new
      gene, experimental proof is required to validate the causality of the variant;
      occasionally, an incidental finding with possible clinical significance is
      identified, raising serious ethical concerns. In this article, we will review the
      use of this technology through the experience of three pediatric departments at
      Hadassah.

PMID- 29582953
TI  - [TO BE A RESIDENT IN THE DEPARTMENT OF MEDICINE].
AB  - INTRODUCTION: Sir William Osler is considered to be one of the fathers of modern
      medicine who pioneered the practice of bedside teaching of clinical medicine for
      medical students and residents. Osler was well known as a diagnostician and
      outstanding therapist with a humanized approach and rare didactic capabilities.
      Medical training at Hadassah is built on the central tenets of Osler's approach,
      incorporating the tremendous advances in science and medicine. Training for
      residents in Internal Medicine is designed to develop a broad base of medical
      and, if possible, scientific knowledge, as well as skills and competencies to
      deliver a high standard of patient care. In the past 7 years, 28 residents have
      undergone specialist training in Internal Medicine B. Among them, 71% were
      Israeli medical school graduates; 36% were women;18% were recent immigrants to
      Israel; 78% were Jewish. Among Jewish residents, 32% were religiously observant.
      Besides the usual assignments of the internal medicine ward, the medical staff of
      Internal Medicine B excelled in diagnosis of hard to diagnose diseases as
      described in eleven cases. The diagnosis in some of those cases was a result of
      listening to the patient, education on clinical reasoning and the use advanced
      diagnostic tools. The basic unit of the residency is the clinical mission with an
      emphasis on exposure to novel modalities such as the use of bedside ultra sound
      along with dealing with end-of-life dilemmas, the management of complex
      situations and development of communication and interpersonal skills needed to
      work with close relatives and families facing critical times. The medical
      training in the internal ward is not just the sum of arbitrary care of the
      hospitalized patients, but a well-structured plan with gradually increasing
      demands. Over the past 7 years, residents in Internal Medicine B have achieved
      successful passing grades of 38/38 on the first attempt oral and written board
      examinations, a record that attests to the quality of the trainees and the
      training process. Hadassah has a long history of providing state-of-the-art
      patient care, and training young physicians to maintain this high standard - but
      the education process necessitates longstanding efforts and continuous striving
      for excellence.

PMID- 29582954
TI  - [Conflict of interests in medicine, research and pubilcation].

PMID- 29582955
TI  - [Editorial].

PMID- 29582956
TI  - [Medicine and Nephrology from Social Networks].

PMID- 29582957
TI  - [Renal manifestation of Autosomal Dominant Polycystic Kidney Disease].
AB  - Autosomal dominant polycystic kidney disease affects over 12 million people in
      the world and is the fourth cause of ESRD. It is the main monogenic kidney
      disease and causes the progressive formation of cysts leading to renal failure
      after a few decades. The main manifestations of the disease are observed even at
      a young age. The early sign of ADPKD is impaired urinary concentrating capacity,
      due to medullary alteration by cysts, and resistance to vasopressin. These
      anatomical alterations determine hyperfiltration, altered ammonium transport,
      nephrolithiasis, and, above all, hypertension even in pediatric age. Activation
      of the renin-angiotensin-aldosterone system has been shown responsible for the
      maintenance of high pressure values as well as the growth of cysts and renal
      fibrosis. Arterial hypertension would be responsible for ventricular hypertrophy.
      Many recent studies have confirmed the role of pressure control, especially if
      rigorous, in decreasing the progression of renal disease, and the use of ACE
      inhibitors seems to have higher efficacy than other antihypertensive drugs. The
      progression of renal disease is evidenced by the reduction of glomerular
      filtration which may be minimal in the early years, due to hyperfiltration, but,
      then, may even exceed 5 ml / min per year, especially when the total kidney
      volume (TKV) exceeds 1500 ml. In more rapid progression forms, ESRD may appear at
      about 55 years of age. The main risk factors are age, genetic mutation,
      familiarity with ESRD, macrohematuria episodes, and early onset hypertension.
      Some authors have proposed both genetic and clinical scores that can provide
      guidance on the probability of rapid progression. Other renal manifestations
      include kidney pain, nephrolithiasis, urinary tract infections and cyst
      hemorrhage. Renal cell carcinoma is a very rare event.

PMID- 29582958
TI  - [CKD-MBD in Peritoneal Dialysis].
AB  - CKD-MBD is a systemic disorder of the mineral and bone metabolism as a result of
      CKD. The clinical relevance of this syndrome has led to the identification of the
      biochemical targets to be achieved in order to improve the outcome of the
      patient. However, in hemodialysis (HD) and peritoneal dialysis (DP) patients,
      these targets are not reached. Hyperphosphatemia is a predictor of cardiovascular
      and all-cause mortality. In DP the removal of phosphorus (P) occurs by diffusion
      and convection, with a contribution of ultrafiltration of about 11%. P clearance
      is time dependent, with differences between CAPD and APD and depending on
      membrane transport characteristics. Residual renal function plays a key role in
      the P balance. Calcium (Ca) clearance in PD depends on the calcium levels,
      calcium concentration in dialysate and ultrafiltration. Positive Ca balance
      brings to Adynamic Bone Disease. Several bone-derived substances, some of them
      with hormonal action, have shed new light on the bone- cardiac axis. The hormonal
      functions of bone are likely to be related to histological lesions that develop
      during chronic renal failure. Compared to the past, recent data show less obvious
      differences in bone histomorphometry parameters between HD patients and PD
      patients. However, in PD patients fewer fractures are reported, probably due to
      different bone quality.

PMID- 29582959
TI  - [A cause of acute renal dysfunction: a giant bladder diverticulum].
AB  - We describe the case of a previously 77-year-old man who accessed in our
      Nephrology Unit for acute kidney injury (AKI) on chronic kidney disease (CKD),
      gastric discomfort and vague urinary symptoms with apparently preserved diuresis
      and suspected "ascites". Physical examination confirmed the presence of abdominal
      effusion, even though ultrasound abdominal examination revealed the presence of a
      giant diverticular urinary bladder with bilateral hydronephrosis. We discuss the
      diagnostic and therapeutic approach of these rare complications by briefly
      reviewing the technical aspects and the possible consequences.

PMID- 29582960
TI  - [Acute kidney injury and rhabdomyolysis after cocaine overdose: case report and
      literature review].
AB  - Cocaine, a natural alkaloid derived from the coca plant, is one of the most
      commonly used illicit drugs. Cocaine abuse causes systemic adverse effects like
      stroke, myocardic infarction, arterial dissection, vascular thrombosis and
      rhabdomyolysis. Cocaine use is, also, associated with renal complications such as
      acute kidney injury, vasculitis, acute interstitial nephritis, chronic kidney
      disease, malignant hypertension with thrombotic microangiopathy. Acute kidney
      injury may or may be not associated to rhabdomyolysis. Rhabdomyolysis caused by
      cocaine abuse is multifactorial, involving tissue ischemia secondary to
      vasoconstriction and cellular damage caused by the drug. We report a 50-year-old
      man with history of chronic hepatitis C and substance abuse admitted to our unit
      with severe rhabdomyolysis and acute kidney failure after nasal insufflation of
      cocaine overdose. Renal function recovered after several treatments of dialysis.
      We conclude that cocaine adversely impacts kidney function ; in addition cocaine
      and rhabdomyolysis are the double danger for acute kidney injury. Medical
      management of cocaine toxicity requires a multisystem approach, with close
      monitoring cardiac, neurological and renal function.

PMID- 29582961
TI  - [Case of sialadenitis by iodinated contrast medium in a dialysis patient].
AB  - Background: Sialadenitis by iodinated contrast medium (i.c.m) oriodine mumps (IM)
      is a rare and late benign manifestation that occurs independently of intravenous
      or endoarterial administration modality. If renal function is normal, i.c.m. does
      not reach salivary glands concentrations able to induce sialadenitis. However, a
      critical glomerular filtration reduction may lead to salivary ducts edema and
      glandular swelling after i.c.m. injection. We report a rare case report of IM in
      a patient on chronic hemodialysis. Methods: A 72-year-old woman affected by
      chronic kidney disease on chronic hemodialysis, underwent to endoscopic removal
      of a rectal cancer. For disease staging, a total body TC with i.c.m. was
      performed. The following morning, patient showed a soft and aching bilateral
      paroditidis swelling. Salivary glands ultrasound was diagnostic for sialadenitis.
      The patient was rapidly treated with betamethasone following by a 240 minutes
      post-dilution online hemodiafiltration session. Results: Within the next 24h, a
      complete remission of IM was obtained. Conclusion: In our patient, a compensatory
      hyperactivity of the sodium / iodine symporter (NIS) on salivary gland cells may
      have played a crucial role in IM induction. An high efficiency hemodialysis
      session within the few following hours after i.c.m injection is a fundamental
      tool in patients on renal replacement treatment to prevent IM that is an
      epiphenomenon of i.c.m. accumulation.

PMID- 29582962
TI  - [Atypical Hemolitic Uremic Syndrome after administration of Docetaxel].
AB  - The purpose of this study is to describe the clinical case of a patient suffering
      from a gland carcinoma with bilateral inguinal and pelvic lymph node metastases
      in treatment with weekly administrations of Docetaxel. After two therapy cycles,
      the patient developed an atypical uremic hemolytic Syndrome (SEUa), treated with
      infusions of frozen fresh plasma, hemodialysis, and antibiotics. Because of a
      severe septic secondary complication on an extensive lymph node abscess, the
      administration of Eculizumab was not possible. The patient survived the mentioned
      Syndrome and is currently in periodic dialysis treatment.

PMID- 29582963
TI  - [Day of Prevention of Renal Diseases in Amatrice, Italy].
AB  - Chronic kidney disease (CKD) is a very common condition and its prevalence is
      increasing worldwide. The CARHES study in Italy showed a prevalence of 6.5% in
      women and 7.5% in men. As a matter of fact, an early diagnosis is essential to
      slow down the progression and improve the renal and cardiovascular prognosis. For
      this purpose the A.N.Di.P. association (National Association of Peritoneal
      Dialysis-Onlus "Enzo Siciliano ") organized the DAY OF PREVENTION OF RENAL
      DISEASES which was held in AMATRICE the 15th of July 2017 called "WE START A NEW
      PATH OF LIFE TOGETHER". The goal of this initiative was to highlight and spread
      the importance of prevention and early diagnosis of renal disease in Amatrice and
      its surroundings. During this day, medical history, blood pressure measurements,
      urinalysis, serum creatinine and serum uric acid were carried out and we
      suggested to patients how to proceed, if necessary, in a further diagnostic and
      therapeutic process. We also recommended a correct lifestyle, based on healthy
      eating and regular physical activity. The choice to dedicate particular attention
      to the population tragically affected by the earthquake occurred to identify
      renal diseases, since they are a possible consequence of the earthquake, to draw
      attention to the importance of renal function and to demonstrate that simple
      routine checks may lead to an early diagnosis of unrecognized kidney diseases,
      also reducing cardiovascular risk.

PMID- 29582964
TI  - [The "Nephrology outpatient Triage": an organizational model for the ambulatory
      care of patients with advanced renal disease].
AB  - The clinical course of outpatients with advanced chronic kidney disease requires
      a close monitoring by the nephrology team, in order to identify emerging clinical
      problems promptly and prevent subsequent complications. With the aim of improving
      the outpatient management in our clinic dedicated to advanced renal failure, we
      implemented the "Nephrology Clinic Triage" (NCT). This organizational model is
      coordinated by the nephrologist and supported by nurses. In case the outpatients,
      or their caregivers, have clinical problems or need advice, they can easily get
      in touch with a nephrology nurse by a dedicated telephone line. The nurse, who
      had been specifically trained for this purpose, interviews the patient by
      telephone and track his health conditions using dedicated flow-charts. The
      patients must be able to answer in a suitable way to the telephone interview on
      which NCT is based. Therefore, all patients referring to nephrology clinic are
      trained to record and report properly by telephone some relevant clinical
      parameters (i.e., blood pressure, body temperature, heart rate, body weight,
      urine volume) and clinical signs (dyspnea, dysuria, diarrhea, nausea, vomiting,
      abdominal/lumbar/chest pain). On the basis of the information obtained by means
      of NCT, the nurse can identify the patient's need and classify its severity and
      priority by means of a color-coding system. The subsequent medical intervention
      (telephone conversation, scheduled appointment, hospitalization) is planned
      accordingly. The implementation of NCT may be useful to monitor the clinical
      course of outpatients with advanced chronic renal failure also when they are
      home, thereby reducing the risk of harmful complications and hospitalization.

PMID- 29582965
TI  - [Screening Test of Fabry Disease in Patients with Renal Replacement Therapy in
      the City of Modena].
AB  - Background: Fabry disease is a rare genetic lysosomal storage disease, inherited
      in an X-linked manner, characterized by lysosomal deposition of
      globotriaosylceramide due to deficient activity of the enzyme alpha-galactosidase
      A. Because the prevalence of this genetic disorder is unknown in the Emilia
      Romagna region, we conducted a screening study to assess the prevalence of Fabry
      disease in the city of Modena, Italy. Material and Methods: A screening study has
      been conducted in patients on renal replacement therapy at University Hospital of
      Modena. Screening tests have been performed using dried blood spot method. Alpha
      galactosidase A activity and Lyso-Gb3 levels were evaluated in peripheral blood
      of all men. In women test based on genetic analysis; Lyso-Gb3 was measured only
      in patients with mutation of gene GLA. Results: Screening tests have been
      performed on 388 subjects: 181 maintenance hemodialysis patients, 166 kidney
      transplant recipients and 41 peritoneal dialysis patients. About 40% of the
      patients did not had etiological diagnosis of renal disease. Lyso-Gb3 was more
      specific test than alpha- galactosidase A (100% vs. 82.5%) to diagnose Fabry
      disease. We found two different mutations: c.13 A >G p.(Asn5Asp), a variant
      likely benign and c.937 G >T p.(Asp313Tyr) a variant of uncertain significance.
      Both the patients carrying these genetic mutations had no symptoms or medical
      history compatible with Fabry disease. Conclusion: Identification of variant of
      uncertain significance such as c.937G >Tp.(Asp313Tyr) showed the limits of
      genetic analysis to diagnose an inherit disease. Further studies are need to
      assess the diagnostic value of Lyso-Gb3 for screening for Fabry disease.

PMID- 29582966
TI  - [Extra-hepatic manifestations associated with Hepatitis and virus infection].
AB  - Hepatitis E virus (HEV) is a significant public health problem that affects
      almost 20 million individuals annually and cause acute liver injury in 3,5
      million. Hepatitis E virus can cause acute, fulminant and chronic hepatitis and
      has been associated with a range of extrahepatic manifestation. The spectrum of
      these manifestation is still emerging. Acute pancreatitis and neurological,
      renal, hematologic, and muscoloskeletal manifestations have been described. Renal
      injury include membranoproliferative glomerulonephritis with or without
      cryoglobulinemia, membranous glomerulonephritis and tubular necrosis. The
      etiopathogenesis of extrahepatic manifestation is only supposed. It could be
      caused by a direct tossic effect of HEV or by an autoimmune process. We report a
      case of a 46 years old man who presented with acute hepatitis E. He was diagnosed
      to have acute severe renal failure and severe pancreatitis due to hepatitis E.
      Few cases have been reported in the literature concerning patients suffering from
      hepatitis E and severe extraepatic manifestations with a benign course and
      complete recovery.

PMID- 29582967
TI  - [Data Protection Officer and Freedom of Information Act].

PMID- 29582968
TI  - Tubular resection of a deep-seated motor cortex lesion.

PMID- 29582969
TI  - Incidence and risk factors of neurosurgical site infections: results of a
      prospective multicenter cohort study on 6359 surgeries.
AB  - OBJECTIVES: Neurosurgical surgical site infections (SSI) are life-threatening
      complications, requiring medical treatment and additional surgeries and remain a
      substantial cause of morbidity. In order to identify the incidence and the main
      risk factors for SSI, we developed the Prophylaxis with Antibiotic protocol for
      neuroSurgical Site Infections Study (PASSIS), a prospective observational
      multicenter cohort study for examining a large number of neurosurgical
      procedures. METHODS: The study PASSIS involved four Italian Neurosurgical
      Departments applying the same antibiotic prophylaxis (ABP) protocol on 6359
      consecutive neurosurgical procedures. In high-risk conditions (intra-operative
      contamination and/or post-operative cerebro-spinal fluid (CSF), and/or
      subcutaneous drainage and/or post-operative hyperpyrexia), and in presence of
      wound complication (CSF leak and/or CSF collection and/or wound diastasis), a
      prolongation protocol was prescribed. RESULTS: The crude rate of SSI in the whole
      series was and 1.7% for patient and 1.5% for procedure. Patient related SSI risk
      factors: Younger patients (<=14 years) had a significantly higher SSI risk
      compared with older patients (RR: 2.17; CI 95%: 1.13- 4.14). Patients underwent
      two surgeries were at increased SSI risk (RR: 3.80; CI 95% 2.33-6.18), and the
      risk increased with the number of surgeries. Surgeries lasting longer than 3
      hours (RR: 2.27; CI 95% 1.15-4.50), undergoing two or more surgeries and the
      presence of prosthetic implants (RR: 2.40; CI 95% 1.53- 3.77) were procedure
      related SSI risk factors positively associated with SSI. In high-risk conditions
      and in wound complication as defined previously, ABP prolongation showed limited
      efficacy (RR:1.97; CI 95% 1.21-3.22 and 9.31; CI 95% 5.90-14.68 respectively).
      CONCLUSIONS: The subjects submitted to complicated, repeated, long lasting
      craniotomies, especially if experiencing postoperative deterioration, display the
      higher risk of SSIs, as a final life threatening complication. In order to reduce
      the SSI rate, further studies should address to design tailored prophylaxis
      protocols for each high risk situation as hereby defined; the wound complications
      deserve an increased microbiological surveillance, focusing the attention on the
      timing and source of infections.

PMID- 29582970
TI  - Use of 4K resolution in endoscopic endonasal neurosurgery: our experience.

PMID- 29582971
TI  - Proton beam radiation-induced glioblastoma multiforme.

PMID- 29582972
TI  - A new method of skin disinfection for spinal surgery: a prospective study on 918
      patients. Our results.

PMID- 29582973
TI  - Transforaminal percutaneous endoscopic lumbar discectomy: outcome and
      complications in 270 cases.
AB  - BACKGROUND: The endoscopic approach has been introduced in the clinical practice
      in 1980 with the aim to remove the pro- lapsed disk and free the compressed nerve
      using the least disruptive surgical technique, assuring in the same time, the
      resolution of the symptoms and a faster return back to normal life activity. Over
      the years, thanks to an extraordinary technical improvement either in terms of
      quality of images and development of many dif- ferent tailored instrumentations
      there has been a huge spreading of the endoscope use across the different
      surgical fields. For this reasons the transforaminal percutaneous endoscopic
      lumbar discectomy can be con- sidered, at the moment, the least invasive
      procedure for the removal of lumbar disc prolapsed. The aim of this study was to
      analyze the clinical outcome and complications rate on a large cumulative series
      operated on in two years period. METHODS: We present a retrospective series
      involving 270 cases of lumbar disk herniation managed surgically only by a
      percutaneous transforaminal endoscopic technique in two units and by two
      surgeons. All patients have a minimum follow-up of 6 months. Primary study end
      points were evaluation of out- comes using the Visual Analogue Scale and Oswestri
      Disability Index pre-operatively and at 3, 6 and 12 month as well as the
      complications and the recurrence rates. RESULTS: Our results, with a positive
      outcome around 93%, confirm the effectiveness of transforaminal per- cutaneous
      endoscopic discectomy in the treatment of lumbar disc herniation when compare to
      open microdiscectomy. Also the complications (5,5%) and the recurrence rate
      (4,1%) can be considered within the standard results. CONCLUSIONS: The
      transforaminal percutaneous endoscopic lumbar discectomy is a safe and effective
      procedure to treat lumbar disc prolapsed. Surgical experience and correct
      patients' selection are crucial factors affecting the outcome.

PMID- 29582974
TI  - Contemporary tools in arteriovenous malformations surgery.
AB  - Arteriovenous malformations (AVMs) are rare entities and therefore considered the
      main challenge for a neurosurgeon. Since the publication of the ARUBA study, one
      of the most popular debate regards the actual surgical indication for unruptured
      AVMs. Our group recently published a multicenter review of more than 500 cases
      underlying the important role of surgery. Over the last few decades, the
      expanding technologies used in the treatment of AVMs have shown an ongoing
      improvement overcoming some of the existing difficulties and shortcomings. In
      this paper, we reviewed the present literature to illustrate the main
      contemporary tools that, in our opinion, are crucial to obtain the best surgical
      and clinical outcome. Indocyanin green is nowadays considered a gold standard to
      identify arterial feeders, draining veins, and to detect any eventual residual.
      The use of non-stick, bipolar, 2-mm blade microclips, and thulium laser allows to
      obtain a better bleeding control and nidus removal. The development of the
      intraoperative ultrasound with neuronavigation, angiosonography, and color
      Doppler improves the accuracy of AVM resection. Moreover, improvements have been
      developed with the use of intraoperative micro-Dopplers combined with flow
      measurements, which consent to verify the gradual reduction of flow through
      draining veins. The possibility to perform functional preoperative studies and
      intraoperative monitoring can be considered as an essential point in the decision
      making in eloquent or near-eloquent AVMs. Furthermore, the hybrid operating room
      represents the best expression of an excellent neurovascular team where the use
      of the intraoperative angiography allows neurosurgeons and neurointerventional
      radiologists to work at the same time in a combined approach to achieve the best
      surgical removal.

PMID- 29582975
TI  - Feasibility of endoscopic endonasal approach for clip application of cerebral
      aneurysms: a systematic review.
AB  - INTRODUCTION: While open, microsurgical clipping and endovascular coiling remain
      the gold standards for treatment of cerebral aneurysms, a growing number of
      aneurysms treated via endoscopic endonasal methods have been reported in the
      literature. The aim of this study was to conduct a systematic review of the
      literature to gain a more thorough appreciation of the potential benefits and
      drawbacks of the endoscopic endonasal strategy in this setting. EVIDENCE
      ACQUISITION: We performed a detailed systematic review of the medical literature
      on endoscopic endonasal skull base surgery for treatment of cerebral aneurysms
      utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines. We identified 9 clinical studies describing treatment of 23
      aneurysms utilizing the EEA. 11 additional cadaveric studies investigating
      aspects of operative exposure and/or technique in this setting were identified.
      The full text of these articles was reviewed. EVIDENCE SYNTHESIS: In the 9
      clinical studies that met inclusion criteria, 23 aneurysms were treated in 21
      patients. The mean patient age was 52.6 years. 15 aneurysms were unruptured and 8
      were ruptured. 14 aneurysms involved the anterior circulation and 9 involved the
      posterior circulation. In 21 of 23 aneurysms, complete occlusion was achieved
      with endonasal clipping. Two aneurysms required additional treatment that
      included a takeback for clip repositioning and staged endovascular coiling.
      Complications included post-operative CSF leak (23.8%), stroke (19%), and
      meningitis (14.3%). Analysis of the combined literature revealed a significantly
      higher rate of CSF leak with endonasal clipping of posterior circulation
      aneurysms compared to anterior circulation aneurysms (P=0.047, Fisher's Exact
      Test). While there was a trend towards increased post- operative neurologic
      deficit following EEA for posterior circulation aneurysms, this did not reach
      statistical significance (P=0.063). The majority of post-operative complications
      in posterior circulation aneurysms occurred during clip application of aneurysms
      at the level of the basilar apex. In addition to the aforementioned clinical
      reports, 11 cadaveric studies were identified. 4 of these reports investigated
      approaches for individual anterior circulation aneurysms, 5 investigated
      approaches for posterior circulations aneurysms, and 2 involved both anterior and
      posterior circulation aneurysms. CONCLUSIONS: Despite a moderate increase in
      utilization, caution should be exercised when choosing an endonasal strategy for
      treatment of aneurysmal pathology over more traditional and established methods
      such as microsurgical clip application and endovascular methods. Anecdotal
      evidence suggests that inferior and/or medial projecting aneurysms involving the
      paraclinoid ICA not amenable to traditional open/endovascular strategies may be
      reasonable to consider for EEA clip application. Wide-necked, midline,
      ventrolaterally-projecting aneurysms involving the vertebrobasilar system may
      represent an additional exception, as long as the location along the rostrocaudal
      axis is low enough so as not to compromise visualization. Future improvements in
      operative technology, including anticipated advances in endoscopic 3-D
      visualization, may further alter the landscape of treatment involving this
      complex pathology.

PMID- 29582976
TI  - Radiosurgery and radiotherapy for arteriovenous malformations: outcome predictors
      and review of the literature.
AB  - Arteriovenous malformations (AVMs) are rare congenital vascular pathologies. The
      reported overall annual hemorrhage rate is 3.0%, for unruptured AVMs it is 2.2%,
      and for ruptured AVMs, 4.5%. The main goal of AVM treatment is to prevent
      intracerebral hemorrhage. This is achieved by complete nidus eradication.
      Interventional treatment options include microsurgery, embolization and
      radiosurgery, as well as multimodal approaches. Radiosurgery is a safe and
      effective alternative to surgery or embolization, especially for AVMs located in
      deep or eloquent brain regions, where invasive treatment cannot be performed.
      With the introduction of the Leksell Gamma Knife, AVMs became one of the most
      common indications for radiosurgical interventions (nearly 30% of the first 15
      year experience). The current review discusses the role of radiosurgery in the
      treatment of AVMs, with a focus on outcome predictors and a discussion of the
      relevant literature.

PMID- 29582977
TI  - Surgical technique and nuances in ruptured versus unruptured arteriovenous
      malformation surgery.
AB  - Because of the more frequent use of noninvasive imaging methods, arteriovenous
      malformation (AVM) are gaining more attention. Population based studies reveal
      that about 35% to 50% of patients with AVM initially present with hemorrhage.
      Prior hemorrhage is the most consistent risk factor for future hemorrhage, other
      risk factors include deep venous drainage pattern, deep location, and so on.
      Surgical interventions, including surgical excision, intravascular intervention,
      and stereotactic radiation, have been developed with the aim to eliminate this
      source of hemorrhage. Among these methods, surgical excision was considered to be
      the gold standard for low grade intracranial AVMs. In ruptured AVMs, it is
      standard to wait several weeks to allow for patient recovery, hematoma
      liquefaction, and inflammatory reactions to subside, except for the life
      threatening hemorrhage. By separating the nidus from adjacent brain (the combined
      effects of the hematoma cavity and encephalomalacia), the hematoma creates a
      space for operator and facilitates AVM resection actually. There are some
      surgical nuances in ruptured versus unruptured AVM surgery. Detailed preoperative
      preparation is necessary to evaluate the general situation, neurological status,
      AVM architecture characteristic before surgery. Essential assistant technique,
      reasonable strategy and meticulous operative skill are crucial for the safety and
      validity of AVM resection.

PMID- 29582978
TI  - Postoperative management and follow-up after resection of arteriovenous
      malformations.
AB  - Arteriovenous malformation (AVM) of the brain is a rare condition with an
      estimated incidence rate of 2.05 cases per 100,000 person-years,1 primarily
      treated in specialized clinics. To prevent AVM from bleeding, treatment via
      microsurgery, Stereotactic Radiosurgery or Endovascular Embolism can be
      undertaken. The success of surgically treated patients largely depends also on
      the proper postoperative management of the patient. This review will focus on the
      postoperative management after surgical treatment with specific emphasis on the
      unique condition in patients with an Arteriovenous Malformation, imaging routine
      postoperatively and follow-up after microsurgical resection of an AVM, presenting
      the current state in the literature. Here, the focus shall be on so called low
      grade AVM, namely Spetzler-Martin grade I and II, which are preferably treated
      surgically rather than radiosurgical or endovascular.

PMID- 29582980
TI  - Embolization before stereotactic radiosurgery for the treatment of brain
      arteriovenous malformations.
AB  - Embolization is commonly used for the treatment of brain arteriovenous
      malformations (AVMs) prior to stereotactic radiosurgery (SRS). Due to mixed
      outcomes, however, its use remains controversial. This article is a review of
      recent studies assessing the efficacy of pre-radiosurgical embolization for brain
      AVMs. Articles published between 1990 and 2017 on the subject of pre
      radiosurgical AVM embolization were retrieved from PubMed. A literature review
      was performed on the selected studies to compare obliteration, hemorrhage, and
      complication rates from groups treated with embolization prior to radiosurgery to
      those treated without embolization. Overall, the studies reviewed demonstrate
      mixed results on the efficacy of pre-radiosurgical AVM embolization. For large,
      complex AVMs, embolization prior to radiosurgery may have a role in carefully
      selected patients performed by experienced practitioners.

PMID- 29582979
TI  - Contemporary endovascular techniques for the curative treatment of cerebral
      arteriovenous malformations and review of neurointerventional outcomes.
AB  - INTRODUCTION: Since the first landmark randomized trials on unruptured bAVMs were
      published, there has been emerging concerns about the role of endovascular
      therapy. For bAVMs considered inoperable, embolization remains an option worth
      considering, especially in young patients presenting with a rupture. We aimed to
      review the curative potential of contemporary stand-alone embolization techniques
      enabling high occlusion rates and their respective short and long term safety
      profile. EVIDENCE ACQUISITION: We performed a PubMed search with the terms
      "curative embolization of brain arteriovenous malformations" and "endovascular
      cure of brain arteriovenous malformations" focusing on the last ten years (2008
      2018) and compliant to the PRISMA reporting guidelines. We then screened the
      prospective and retrospective studies of pediatric or adult populations that
      contained patient demographics, ruptured or unruptured presentation, and bAVM
      grade according to the Spetzler-Martin (SM) classification, exclusive or stand
      alone endovascular treatment without previous embolization, micro-, radio- or
      stereotactic surgery, number of sessions, type of access, technique(s) and
      embolic agents used, rate of angiographically confirmed complete occlusion at
      least 3 months after obliteration stratified by AVM grade or subtype, as well as
      neurological status and treatment-associated outcome based on the modified Rankin
      scale at admission, discharge and within 12 months following curative
      embolization, rated by an independent observer. EVIDENCE SYNTHESIS: Given the
      heterogeneity of the reported data, multiple confounding factors, overwhelming
      number of unpowered studies, lack of homogenous control groups and poor
      compliance to PRISMA reporting guidelines in most of the interventional
      literature, we were unable to obtain solid data and perform a statistical meta
      analysis on the safety and effectiveness of curative embolization. Consequently,
      we decided to cover a selection of salient topics. CONCLUSIONS: Stand-alone
      curative embolization, as well as exclusive microsurgery or radiosurgery each
      play complementary roles. Hemorrhagic, deep-seated lesions are an interesting
      subtype of surgically unfavorable bAVMs that may benefit from exclusive
      transvenous embolization, when carefully selected. Larger randomized trials and
      prospective registries are needed to establish the place of stand-alone or
      neoadjuvant endovascular treatment.

PMID- 29582981
TI  - Predicting outcomes after severe traumatic brain injury: science, humanity or
      both?
AB  - Predicting long-term outcome after severe traumatic brain injury (TBI) is
      difficult, but accurate assessment is paramount for both families of the patients
      and medical decision-making, as well as quality assurance or research purposes.
      Many important prognostic factors for patients with severe TBI have been
      identified, but most - if not all - including the Glasgow Coma Score and magnetic
      resonance imaging are not accurate enough to be used alone to predict patient
      outcomes. Clinicians should also be wary about how their predictions and decision
      making can be affected by heuristics and cognitive biases. Well-validated
      prognostic models, including the CRASH and IMPACT models, are easily available
      and, provided their limitations are appreciated, they offer an enormous potential
      to assist clinicians to objectively prognosticate the outcomes of patients with
      severe TBI by reducing the unduly influence of subconscious heuristics and
      cognitive biases. Finally, we also should not underestimate human being's
      adaptability, including their ability to recalibrate what may be acceptable to
      them when life circumstances have changed. Predicting outcome and decision-making
      after severe TBI requires a deep understanding of both science and humanity - a
      task we should all take seriously.

PMID- 29582983
TI  - [Ignorance as potential knowledge].
AB  - This article invites us to think about the learning process, giving special
      attention to what we do not know, the recognition of ignorance, and the
      activation of the desire to learn.  It proposes to revisit the mental patterns
      that might interfere with the learning process.  To go beyond the Newton thought
      and to develop instead a thinking process that can be dual and quantic, which
      allows us to elucidate and comprehend complex situations.

PMID- 29582982
TI  - [Ramadan and diabetes mellitus in adult muslim population].
AB  - Background: Although sick people are exempted from performing Ramadan, it is
      estimated that approximately 50 million people with diabetes mellitus (DM) fast
      during this month. Objective: To explore the relationship between Ramadan and DM
      in adult Muslim population as well as management and recommendations from
      literature related with this issue. Method: A narrative review was carried out in
      PubMed, Cochrane and Cuiden, databases, using controlled and free language for
      the period 2009-2014, and language filters (Spanish and English). Content
      analysis of selected documents in order to find emerging thematic categories was
      conducted. Results: The results have been organized into five thematic
      categories: the desire for Ramadan; changes that occur in the body by fasting;
      complications from fasting; control of DM during fasting; knowledge of healthcare
      professional. Conclusion: Those believers who wish to take part in Ramadan and
      suffering DM, have to go to their health care professional before performing
      because, although people with good control can perform the fast, the treatment
      must be individualized, considering the composition and amount of food they are
      going to eat.

PMID- 29582984
TI  - Controlling Octagon-to-Square Wetting Interface Transition of Evaporating Sessile
      Droplet through Surfactant on Microtextured Surface.
AB  - Producing and maintaining specific liquid patterns during evaporation holds great
      potential for techniques of printing and coating. Here we report the control over
      the evolution of surfactant solution droplets on the micropyramid substrates
      during evaporation. The polygonal droplet shape is achieved during the drying
      rather than solely at the beginning. As the initial surfactant concentration is
      0.04 mM, the droplet maintains its initial octagonal shape throughout the
      lifetime. Interestingly, the initial octagonal shape transforms into a square
      during the evaporation as the initial surfactant concentration reaches 0.8 mM.
      These findings can shed light on wetting pattern control for complex solutions
      required in various applications.

PMID- 29582985
TI  - Core-Satellite Supraparticles To Ballistically Stamp Nanostructures on Surfaces.
AB  - Nanostructured surfaces are of great importance in a very wide range of fields.
      They can be obtained by imprint or deposition techniques. However, these are
      usually sophisticated to perform. Generally, it is not easy to equip an
      object/product with a nanostructure after manufacturing. Yet, it would be very
      beneficial to achieve a modification of an arbitrary surface with a nanostructure
      of choice at a later stage by an approach that is simple to perform without the
      need of sophisticated equipment or excessive treatment by physicochemical
      methods. Herein, such a process is reported, which combines two "old-fashioned"
      techniques, namely, sandblasting and rubber-stamping, and translates them to the
      "nanoworld". By creating core-satellite supraparticles via spray-drying, a
      ballistic core-satellite stamp particle system is obtained, which can be used to
      easily transfer a wide range of nanoparticles to a great variety of surfaces to
      equip these with a nanostructure and subsequently advanced properties. These
      include water-repellant, antifouling, or antidust surfaces. Moreover, it is also
      demonstrated that the approach can be used to manufacture well-defined
      nanoimprinted surfaces. Such surfaces showed an improved spreading behavior for
      aliphatic alcohols, thus making such surfaces, for instance, very susceptible for
      disinfectants. All in all, the simple technique described herein has a great
      potential for creating nanostructured surfaces on nearly any surface.

PMID- 29582986
TI  - Polyoxometalate-Promoted Electrocatalytic CO2 Reduction at Nanostructured Silver
      in Dimethylformamide.
AB  - Electrochemical reduction of CO2 is a promising method to convert CO2 into fuels
      or useful chemicals, such as carbon monoxide (CO), hydrocarbons, and alcohols. In
      this study, nanostructured Ag was obtained by electrodeposition of Ag in the
      presence of a Keggin type polyoxometalate, [PMo12O40]3- (PMo). Metallic Ag is
      formed upon reduction of Ag+. Adsorption of PMo on the surface of the newly
      formed Ag lowers its surface energy thus stabilizes the nanostructure. The
      electrocatalytic performance of this Ag-PMo nanocomposite for CO2 reduction was
      evaluated in a CO2 saturated dimethylformamide medium containing 0.1 M [ n
      Bu4N]PF6 and 0.5% (v/v) added H2O. The results show that this Ag-PMo
      nanocomposite can catalyze the reduction of CO2 to CO with an onset potential of 
      1.70 V versus Fc0/+, which is only 0.29 V more negative than the estimated
      reversible potential (-1.41 V) for this process and 0.70 V more positive than
      that on bulk Ag metal. High faradaic efficiencies of about 90% were obtained over
      a wide range of applied potentials. A Tafel slope of 60 mV dec-1 suggests that
      rapid formation of *CO2*- is followed by the rate-determining protonation step.
      This is consistent with the voltammetric data which suggest that the reduced PMo
      interacts strongly with CO2 (and presumably CO2*-) and hence promotes the
      formation of CO2*-.

PMID- 29582987
TI  - CeF3-Doped Porous Carbon Nanofibers as Sulfur Immobilizers in Cathode Material
      for High-Performance Lithium-Sulfur Batteries.
AB  - In this study, the CeF3-doped porous carbon nanofibers (PCNFs), prepared via
      electroblown spinning technique and carbonization process, are used as sulfur
      immobilizers in cathodes for lithium-sulfur (Li-S) batteries for the first time.
      The cathode composed of CeF3-doped PCNFs, carbon nanotubes (CNTs), and S is
      successfully prepared through the ball-milling and heating method. The formed
      porous structure in the PCNFs and CNTs facilitates the construction of highly
      electrically conductive pathways and effectively alleviates volume changes, which
      can maintain the stability of the cathode structure and make them in close
      contact between the electrodes. Meanwhile, the intermediate polysulfide dissolved
      and lost in the electrolyte can also be suppressed because of the hierarchical
      porous carbon nanofibers and CeF3. The Li-S battery using the cathode can display
      excellent electrochemical properties and stable capacity retention, presenting an
      initial discharge capacity of 1395.0 mAh g-1 and retaining a capacity of 901.2
      mAh g-1 after 500 cycles at 0.5C. During the rate capability tests of battery,
      the discharge capacity of Li-S battery with the electrode slowed down from the
      discharge capacity of 1284.6 mAh g-1 at 0.5C to 1038.6 mAh g-1 at 1C and 819.3
      mAh g-1 at 2C, respectively. It is noteworthy that the battery can still endow an
      outstanding discharge capacity of 1269.73 mAh g-1 with a high retention of 99.2%
      when the current density returns to 0.5C.

PMID- 29582988
TI  - Tuning Pseudocapacitance via C-S Bonding in WS2 Nanorods Anchored on N,S Codoped
      Graphene for High-Power Lithium Batteries.
AB  - Pseudocapacitance plays an important role in high-power lithium-ion batteries
      (LIBs). However, it is still lack of effective methods to tailor the
      pseudocapacitance contribution in electrode materials for LIBs. Herein,
      pseudocapacitance tuned by the strength of C-S bonding has been rendered in WS2
      nanorods anchored on the N,S codoped three-dimensional graphene hybrid (WS2@N,S
      3DG) for the first time. The pseudocapacitive contributions in the charge storage
      can be enhanced effectively with the increased strength of C-S bonding. As
      expected, the enhanced extrinsic pseudocapacitance makes WS2@N,S-3DG a
      fascinating electrode material for high-power LIBs, with a high reversible
      capacity of 509 mA h g-1 over 500 cycles at a current density as high as 2 A g-1.
      These encouraging results of pseudocapacitance tailored by chemical bonding
      provide new opportunities for designing advanced electrode materials.

PMID- 29582989
TI  - Facile Biofabrication of Heterogeneous Multilayer Tubular Hydrogels by Fast
      Diffusion-Induced Gelation.
AB  - Multilayer (ML) hydrogels are useful to achieve stepwise and heterogeneous
      control over the organization of biomedical materials and cells. There are
      numerous challenges in the development of fabrication approaches toward this,
      including the need for mild processing conditions that maintain the integrity of
      embedded compounds and the versatility in processing to introduce desired
      complexity. Here, we report a method to fabricate heterogeneous multilayered
      hydrogels based on diffusion-induced gelation. This technique uses the quick
      diffusion of ions and small molecules (i.e., photoinitiators) through gel-sol or
      gel-gel interfaces to produce hydrogel layers. Specifically, ionically (e.g.,
      alginate-based) and covalently [e.g., gelatin methacryloyl (GelMA-based)]
      photocross-linked hydrogels are generated in converse directions from the same
      interface. The ML (e.g., seven layers) ionic hydrogels can be formed within
      seconds to minutes with thicknesses ranging from tens to hundreds of micrometers.
      The thicknesses of the covalent hydrogels are determined by the reaction time (or
      the molecule diffusion time). Multiwalled tubular structures (e.g., mimicking
      branched multiwalled vessels) are mainly investigated in this study based on a
      removable gel core, but this method can be generalized to other material
      patterns. The process is also demonstrated to support the encapsulation of viable
      cells and is compatible with a range of thermally reversible core materials
      (e.g., gelatin and Pluronic F127) and covalently cross-linked formulations (e.g.,
      GelMA and methacrylated hyaluronic acid). This biofabrication process enhances
      our ability to fabricate a range of structures that are useful for biomedical
      applications.

PMID- 29582990
TI  - In Situ Inner Lumen Attachment of Heparin to Poly(ether sulfone) Hollow Fiber
      Membranes Used for Microdialysis Sampling.
AB  - An in situ chemical surface modification method to attach heparin to the inner
      lumen of a single hollow fiber poly(ether sulfone) (PES) membrane incorporated
      into a commercial microdialysis sampling device is described. The immobilization
      process uses gentle, room-temperature conditions with the enzyme laccase (E.C.
      1.10.3.2) and 4-hydroxybenzoic acid (4HBA). The resulting functionalized inner
      membrane surface with a carboxylic acid functional groups allowed for (1-ethyl-3
      (3-(dimethylamino)propyl) carbodimide)/ N-hydroxysuccinimide) EDC/NHS chemistry
      to attach heparin to the membrane surface. X-ray photoelectron spectroscopy
      measurements suggested successful attachment of 4HBA polymers and heparin onto
      the PES membrane. The microdialysis extraction efficiency after membrane surface
      modification was measured with model compounds fluorescein isothiocyanate (FITC)
      labeled dextrans and lysozyme and the cytokines acidic fibroblast growth factor
      (aFGF) and CXCL1 (KC/GRO). This work demonstrates an in situ method to modify
      commercially available PES hollow fiber microdialysis membranes with amine or
      carboxylic acid functional groups.

PMID- 29582991
TI  - Capacitive Pressure Sensor with High Sensitivity and Fast Response to Dynamic
      Interaction Based on Graphene and Porous Nylon Networks.
AB  - Flexible pressure sensors are of great importance to be applied in artificial
      intelligence and wearable electronics. However, assembling a simple structure,
      high-performance capacitive pressure sensor, especially for monitoring the flow
      of liquids, is still a big challenge. Here, on the basis of a sandwich-like
      structure, we propose a facile capacitive pressure sensor optimized by a
      flexible, low-cost nylon netting, showing many merits including a high response
      sensitivity (0.33 kPa-1) in a low-pressure regime (<1 kPa), an ultralow detection
      limit as 3.3 Pa, excellent working stability after more than 1000 cycles, and
      synchronous monitoring for human pulses and clicks. More important, this sensor
      exhibits an ultrafast response speed (<20 ms), which enables its detection for
      the fast variations of a small applied pressure from the morphological changing
      processes of a droplet falling onto the sensor. Furthermore, a capacitive
      pressure sensor array is fabricated for demonstrating the ability to spatial
      pressure distribution. Our developed pressure sensors show great prospects in
      practical applications such as health monitoring, flexible tactile devices, and
      motion detection.

PMID- 29582992
TI  - Effective Dual Polysulfide Rejection by a Tannic Acid/FeIII Complex-Coated
      Separator in Lithium-Sulfur Batteries.
AB  - The solubility behaviour of polysulfides in electrolyte solutions is a major
      bottleneck prior to the practical application of the lithium-sulfur battery. To
      address this issue, we fabricate a tannic acid/FeIII complex-coated polypropylene
      (PP) separator (TA/FeIII-PP separator) via a simple, fast, and green method.
      Benefiting from dual-confinement effects based on Lewis acid-base interactions
      between FeIII and polysulfides as well as the dipole-dipole interactions between
      rich phenol groups and polysulfides, the migration of polysulfides is effectively
      suppressed. Meanwhile, the porous structure of the PP separator is not destroyed
      by an additional coating layer. Thus, the TA/FeIII-PP separator can retain rapid
      lithium ion transport, eventually leading to a significant improvement in both
      the discharge capacity and rate performance of the corresponding lithium-sulfur
      cells. The cell with the TA/FeIII-PP separator presents a low capacity fade of
      0.06% per cycle over 1000 cycles at 2.0 C, along with a high Coulombic efficiency
      of >97% over 300 cycles at 0.5 C. With respect to the one with the bare PP
      separator, the cell with the TA/FeIII-PP separator exhibits a 1.7-fold increase
      in the discharge capacity at 3.0 C. The proposed simple and economical approach
      shows great potential in constructing advanced separators to retard the shuttle
      effect of polysulfides for lithium-sulfur batteries.

PMID- 29582993
TI  - Carbapenems and Lipid Bilayers: Localization, Partitioning, and Energetics.
AB  - Carbapenems are broad-spectrum antibiotics used today to treat otherwise
      antibiotic resistant bacteria. As their target transpeptidase is located within
      the periplasm of the Gram-negative bacteria, they can participate in nonspecific
      interactions between the inner leaflet of the outer membrane and the outer
      leaflet of the inner membrane. We, therefore, studied the interaction of the four
      most clinically relevant carbapenems, namely, imipenem, doripenem, ertapenem, and
      meropenem, with model phospholipid bilayers made of 1,2-dimyristoyl- sn-glycero-3
      phosphocholine (DMPC) using molecular dynamics (MD) simulations and X-ray
      diffraction at low and high concentration of the drugs corresponding to 1 and 8
      mol % (with respect to the number of membrane lipids). Membrane solubility was
      found to decrease from imipenem to doripenem, ertapenem, and finally meropenem.
      At low concentrations, membrane insertion was found to be a two step process,
      where the drugs first adsorb to the lipid head groups before inserting through a
      rotation of the molecule. At higher drug concentrations, the molecules were found
      to form aggregates in the aqueous phase before making contact with the membranes
      and spontaneously inserting into the bilayers. Two populations of imipenem were
      found: in the headgroup at ~17 A from the bilayer center and an inserted
      population at z-values of about 7 A. Other carbapenems were found to localize in
      the tail groups with meropenem at ~10 A, doripenem at ~8 A, and ertapenem at ~8
      A. The observed membrane solubility of carbapenems can potentially impact the
      availability of the drug to the target penicillin-binding proteins, potentially
      affecting their clinical efficacy.

PMID- 29582994
TI  - Analytical Cascades of Enzymes for Sensitive Detection of Structural Variations
      in Protein Samples.
AB  - Protein function critically depends on structure. However, current analytical
      tools to monitor consistent higher-order structure with high sensitivity, as for
      instance required in the development of biopharmaceuticals, are limited. To
      complement existing assays, we present the analytical cascade of enzymes (ACE), a
      method based on enzymatic modifications of target proteins, which serve to
      exponentially amplify structural differences between them. The method enables
      conformational and chemical fingerprinting of closely related proteins, allowing
      for the sensitive detection of heterogeneities in protein preparations with high
      precision. Using this method, we detect protein variants differing in
      conformation only, as well as structural changes induced by diverse covalent
      modifications. Additionally, we employ this method to identify the nature of
      structural variants. Moreover, the ACE method should help to address the limited
      reproducibility in fundamental research, which partly relates to sample
      heterogeneities.

PMID- 29582995
TI  - Quasi-aromatic Mobius Metal Chelates.
AB  - We report the design as well as structural and spectroscopic characterizations of
      two new coordination compounds obtained from Cd(NO3)2.4H2O and polydentate
      ligands, benzilbis(pyridin-2-yl)methylidenehydrazone (LI) and
      benzilbis(acetylpyridin-2-yl)methylidenehydrazone (LII), in a mixture with two
      equivalents of NH4NCS in MeOH, namely [Cd(SCN)(NCS)(LI)(MeOH)] (1) and
      [Cd(NCS)2(LII)(MeOH)] (2). Both LI and LII are bound via two pyridyl-imine units
      yielding a tetradentate coordination mode giving rise to the 12 pi electron
      chelate ring. It has been determined for the first time (qualitatively and
      quantitatively), using the EDDB electron population-based method, the HOMA index,
      and the ETS-NOCV charge and energy decomposition scheme, that the chelate ring
      containing CdII can be classified as a quasi-aromatic Mobius motif. Notably,
      using the methyl-containing ligand LII controls the exclusive presence of the NCS
      connected with the CdII atom (structure 2), while applying LI allows us to
      simultaneously coordinate NCS- and SCN- ligands (structure 1). Both systems are
      stabilized mostly by hydrogen bonding, C-H...pi interactions, aromatic pi...pi
      stacking, and dihydrogen C-H...H-C bonds. The optical properties have been
      investigated by diffused reflectance spectroscopy as well as molecular and
      periodic DFT/TD-DFT calculations. The DFT-based ETS-NOCV analysis as well as
      periodic calculations led us to conclude that the monomers which constitute the
      obtained chelates are extremely strongly bonded to each other, and the calculated
      interaction energies are found to be in the regime of strong covalent
      connections. Intramolecular van der Waals dispersion forces, due to the large
      size of LI and LII, appeared to significantly stabilize these systems as well as
      amplify the aromaticity phenomenon.

PMID- 29582996
TI  - Conventional-Flow Liquid Chromatography-Mass Spectrometry for Exploratory Bottom
      Up Proteomic Analyses.
AB  - Due to its sensitivity and productivity, bottom-up proteomics based on liquid
      chromatography-mass spectrometry (LC-MS) has become the core approach in the
      field. The de facto standard LC-MS platform for proteomics operates at sub
      MUL/min flow rates, and nanospray is required for efficiently introducing
      peptides into a mass spectrometer. Although this is almost a "dogma", this view
      is being reconsidered in light of developments in highly efficient
      chromatographic columns, and especially with the introduction of exceptionally
      sensitive MS instruments. Although conventional-flow LC-MS platforms have
      recently penetrated targeted proteomics successfully, their possibilities in
      discovery-oriented proteomics have not yet been thoroughly explored. Our
      objective was to determine what are the extra costs and what optimization and
      adjustments to a conventional-flow LC-MS system must be undertaken to identify a
      comparable number of proteins as can be identified on a nanoLC-MS system. We
      demonstrate that the amount of a complex tryptic digest needed for comparable
      proteome coverage can be roughly 5-fold greater, providing the column dimensions
      are properly chosen, extra-column peak dispersion is minimized, column
      temperature and flow rate are set to levels appropriate for peptide separation,
      and the composition of mobile phases is fine-tuned. Indeed, we identified 2 835
      proteins from 2 MUg of HeLa cells tryptic digest separated during a 60 min
      gradient at 68 MUL/min on a 1.0 mm * 250 mm column held at 55  degrees C and
      using an aqua-acetonitrile mobile phases containing 0.1% formic acid, 0.4% acetic
      acid, and 3% dimethyl sulfoxide. Our results document that conventional-flow LC
      MS is an attractive alternative for bottom-up exploratory proteomics.

PMID- 29582997
TI  - Co(III) Complexes with N2S3-Type Ligands as Structural/Functional Models for the
      Isocyanide Hydrolysis Reaction Catalyzed by Nitrile Hydratase.
AB  - It has been before reported that, in addition to hydration of nitriles, the Fe
      type nitrile hydratase (NHase) also catalyzes the hydrolysis of tert
      butylisocyanide ( tBuNC). In order to investigate the unique isocyanide
      hydrolysis by NHase, we prepared three related Co(III) model complexes,
      PPh4[Co(L)] (1), PPh4[Co(L-O3)] (2), and PPh4[Co(L-O4)] (3), where L is bis( N-(2
      mercapto-2-methylpropionyl)aminopropyl)sulfide. The suffixes L-O3 and L-O4
      indicate ligands with a sulfenate and a sulfinate and with two sulfinates,
      respectively, instead of the two thiolates of L. The X-ray analyses of 1 and 3
      reveal trigonal bipyramidal and square pyramidal structures, respectively.
      Complex 2, however, has five-coordinate trigonal-bipyramidal geometry with eta2
      type S-O coordination by a sulfenyl group. Addition of tBuNC to 1, 2, and 3
      induces an absorption spectral change as a result of formation of an octahedral
      Co(III) complex. This interpretation is also supported by the crystal structures
      of PPh4[Co(L-O4)( tBuNC)] (4) and (PPh4)2[Co(L-O4)(CN)] (5). A water molecule
      interacts with 3 but cannot be activated as reported previously, as demonstrated
      by the lack of absorption spectral change in the pH range of 5.5-10.2.
      Interestingly, the coordinated tBuNC is hydrolyzed by 2 and 3 at pH 10.2 to
      produce tBuNH2 and CO molecule, but 1 does not react. These findings provide
      strong evidence that hydrolysis of tBuNC by NHase proceeds not by activation of
      the coordinated water molecule but by coordination of the substrate. The
      mechanism of the hydrolysis reaction of tBuNC is explained with support provided
      by DFT calculations; a positively polarized C atom of tBuNC on the Co(III) center
      is nucleophilically attacked by a hydroxide anion activated through an
      interaction of the sulfenyl/sulfinyl oxygen with the nucleophile.

PMID- 29582998
TI  - A Tribute to George R. Aiken.

PMID- 29582999
TI  - Insights into the Microstructure and Transition Mechanism for Nd3+-Doped
      Bi4Si3O12: A Promising Near-Infrared Laser Material.
AB  - Due to its unusual optical properties, neodymium ion (Nd3+)-doped bismuth
      silicate (Bi4Si3O12, BSO) is widely used for its excellent medium laser
      amplification in physics, chemistry, biomedicine, and other research fields.
      Although the spectral transitions and luminescent mechanisms of Nd3+-doped BSO
      have been investigated experimentally, theoretical research is severely limited
      due to the lack of detailed information about the microstructure and the doping
      site of Nd3+-doped BSO, as well as the electric and magnetic dipole transition
      mechanisms. Herein, we systematically study the microstructure and doping site of
      Nd3+-doped BSO using an unbiased CALYPSO structure search method in conjunction
      with first-principles calculations. The result indicates that the Nd3+ ion
      impurity occupies the host Bi3+ ion site with trigonal symmetry, forming a unique
      semiconducting phase. Based on our newly developed WEPMD method, the electric
      dipole and magnetic dipole transition lines, including a large number of
      absorption and emission lines, in the region of visible and near-infrared spectra
      of Nd3+-doped BSO are calculated. It is found that the 4G5/2 -> 4I9/2, 2H9/2 ->
      4I9/2, and 4F3/2 -> 4I11/2 channels are promising laser actions of Nd3+-doped
      BSO. These findings indicate that Nd3+-doped BSO crystals can serve as a
      promising multifunctional material for optical laser devices.

PMID- 29583000
TI  - Chiral Selenide-Catalyzed Enantioselective Allylic Reaction and Intermolecular
      Difunctionalization of Alkenes: Efficient Construction of C-SCF3 Stereogenic
      Molecules.
AB  - New approaches for the synthesis of enantiopure trifluoromethylthiolated
      molecules by chiral selenide-catalyzed allylic trifluoromethylthiolation and
      intermolecular difunctionalization of unactivated alkenes are disclosed. In these
      transformations, functional groups were well tolerated, and the desired products
      were obtained in good yields with excellent chemo-, enantio-, and
      diastereoselectivities. This reaction is nicely complementary to enantioselective
      trifluoromethylthiolation, allylic functionalization, and intermolecular alkene
      difunctionalization.

PMID- 29583002
TI  - Salt-Induced Control of the Grafting Density in Poly(ethylene glycol) Brush
      Layers by a Grafting-to Approach.
AB  - In this work, a method to obtain control of the grafting density during the
      formation of polymer brush layers by the grafting-to method of thiolated
      poly(ethylene glycol) onto gold is presented. The grafting density of the polymer
      chains was adjusted by adding Na2SO4 in concentrations between 0.2 and 0.9 M to
      the aqueous polymer solution during the grafting process. The obtained grafting
      densities ranged from 0.26 to 1.60 chains nm-2, as determined by surface plasmon
      resonance. The kinetics of the grafting process were studied in situ by a quartz
      crystal microbalance with dissipation, and a mushroom to brush conformational
      transition was observed when the polymer was grafted in the presence of Na2SO4.
      The transition from mushroom to brush was only observed for long periods of
      grafting, highlighting the importance of time to obtain high grafting densities.
      Finally, the prepared brush layer with the highest grafting density showed high
      resistance to the adsorption of bovine serum albumin, while layers with a lower
      grafting density showed only limited resistance.

PMID- 29583001
TI  - Catalytic Diastereo- and Enantioselective Fluoroamination of Alkenes.
AB  - The stereoselective synthesis of syn-beta-fluoroaziridine building blocks via
      chiral aryl iodide-catalyzed fluorination of allylic amines is reported. The
      method employs HF-pyridine as a nucleophilic fluoride source together with mCPBA
      as a stoichiometric oxidant, and affords access to arylethylamine derivatives
      featuring fluorine-containing stereocenters in high diastereo- and
      enantioselectivity. Catalyst-controlled diastereoselectivity in the fluorination
      of chiral allylic amines enabled the preparation of highly enantioenriched 1,3
      difluoro-2-amines bearing three contiguous stereocenters. The enantioselective
      catalytic method was applied successfully to other classes of multifunctional
      alkene substrates to afford anti-beta-fluoropyrrolidines, as well as a variety of
      1,2-oxyfluorinated products.

PMID- 29583003
TI  - Ammonia Activation by Ce Atom: Matrix-Isolation FTIR and Theoretical Studies.
AB  - The activation of ammonia by cerium atom has been investigated in solid argon
      using infrared spectroscopy and density functional theoretical calculations. The
      results reveal that the spontaneous formation of CeNH3 complex on annealing is
      the initial step in the reactions of cerium atoms with ammonia. The CeNH3
      complexes rearrange to generate the inserted HCeNH2 molecules on irradiation. A
      "triplet-singlet" spin conversion occurs along the reaction path in which HCeNH2
      (3A") isomerizes into H2CeNH (1A'). The H2CeNH molecules finally decompose to
      yield HCeN + H2 upon photolysis. The periodic trend and differences for the M +
      NH3 (M = Ti, Zr, Hf, Ce, Th) systems are discussed on the basis of the present
      and previous works. DFT calculations predict that the most stable ground state
      for HHfNH2 and HThNH2 is singlet due to the stronger relativistic effects in Hf
      and Th atoms, while that for HTiNH2, HZrNH2, and HCeNH2 is triplet. Besides, the
      H2-elimination process is different for Ce and M (Ti, Zr, Hf, Th) cases.

PMID- 29583004
TI  - Effects of Stigmasterol and beta-Sitosterol on Nonalcoholic Fatty Liver Disease
      in a Mouse Model: A Lipidomic Analysis.
AB  - To study the effects of stigmasterol and beta-sitosterol on high-fat Western diet
      (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were
      conducted in liver samples collected after 33 weeks of the treatment. Principal
      component analysis showed these phytosterols were effective in protecting against
      HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate
      analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs),
      phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids
      (FFAs) were the major lipid species contributing to these discriminations. The
      alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol,
      TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In
      conclusion, phytosterols, at a dose comparable to that suggested for humans by
      the FDA for the reduction of plasma cholesterol levels, are shown to protect
      against NAFLD in this long-term (33-week) study.

PMID- 29583005
TI  - Flavorings with Modifying Properties.

PMID- 29583006
TI  - Effect of Unsaturation on the Adsorption and the Mechanical Behavior of Fatty
      Acid Layers.
AB  - Adsorption, self-organization, and mechanical properties of different fatty acid
      layers under different confinement states have been investigated as a function of
      the presence and conformation of one unsaturation in their aliphatic chain. In
      situ characterization, at the molecular level, was performed with the ATLAS
      molecular tribometer, in terms of rheology, forces, and thickness of confined
      fluid. The results demonstrate that the fatty acids adsorb on the surfaces by
      weak interactions and form viscoelastic films with a thickness of about 15 A on
      each surface. The adsorption kinetics, the packing of the self-assembled
      monolayers, and the coverage rate depend on the molecular architecture of the
      fatty acids and lead to various mechanical behaviors under confinement.

PMID- 29583007
TI  - Stereocontrolled Synthesis of 2-Deoxy-galactopyranosides via Isopropylidene
      Protected 6- O-Silylated Donors.
AB  - The stereocontrolled synthesis of 2-deoxy-d- arabino-hexopyranosides
      ("galactopyranosides") using 3,4- O-isopropylidene-6- O- tert-butyldiphenylsilyl
      protected glycosyl donors is reported. 2-Deoxy-thioglycoside 3e gives excellent
      alpha-selectivity, while galactal 9 leads to, in a two-step protocol, 2-deoxy
      beta-glycosides in high stereoselectivity. The selectivity of both reagents is
      believed to arise from the combination of the isopropylidene acetal spanning O-3
      and O-4 together with the sterically demanding silyl group on O-6. The utility of
      the method was demonstrated through the synthesis of a trisaccharide that
      contains both 2-deoxy alpha- and beta-d-galactopyranosyl residues.

PMID- 29583008
TI  - Copper-Catalyzed Domino Cyclization/Trifluoromethylthiolation of Unactivated
      Alkenes: Access to SCF3-Containing Pyrrolines.
AB  - A novel and efficient copper-catalyzed cascade
      cyclization/trifluoromethylthiolation of unactivated olefins has been achieved
      with the stable and readily available AgSCF3 as the SCF3 source. A range of SCF3
      substituted pyrrolines have been easily obtained under mild conditions in good
      yields via the present process. This method represents a facile and rapid access
      to valuable pyrrolines with fluorine-containing groups, and it is amenable to
      gram-scale synthesis.

PMID- 29583009
TI  - Hydrogelation Kinetics Measured in a Microfluidic Device with in Situ X-ray and
      Fluorescence Detection.
AB  - Efficient hydrogelators will gel water fast and at low concentrations. Small
      molecule gelling agents that assemble into fibers and fiber networks are
      particularly effective hydrogelators. Whereas it is straightforward to determine
      their critical concentration for hydrogelation, the kinetics of hydrogelation is
      more difficult to study because it is often very fast, occurring on the subsecond
      time scale. We used a 3D focusing microfluidic device combined with fluorescence
      microscopy and in situ small-angle X-ray scattering (SAXS) to study the fast pH
      induced gelation of a model small molecule gelling agent at the millisecond time
      scale. The gelator is a 1,3,5-benzene tricarboxamide which upon acidification
      assembles into nanofibrils and fibril networks that show a characteristic
      photoluminescence. By adjusting the flow rates, the regime of early nanofibril
      formation and gelation could be followed along the microfluidic reaction channel.
      The measured fluorescence intensity profiles were analyzed in terms of a
      diffusion-advection-reaction model to determine the association rate constant,
      which is in a typical range for the small molecule self-assembly. Using in situ
      SAXS, we could determine the dimensions of the fibers that were formed during the
      early self-assembly process. The detailed structure of the fibers was
      subsequently determined by cryotransmission electron microscopy. The study
      demonstrates that 3D focusing microfluidic devices are a powerful means to study
      the self-assembly on the millisecond time scale, which is applied to reveal early
      state of hydrogelation kinetics. In combination with in situ fluorescence and X
      ray scattering, these experiments provide detailed insights into the first self
      assembly steps and their reaction rates.

PMID- 29583010
TI  - Silver-Catalyzed Asymmetric Desymmetrization of Cyclopentenediones via [3 + 2]
      Cycloaddition with alpha-Substituted Isocyanoacetates.
AB  - A highly selective and practical asymmetric Ag(I) catalyst system has been
      developed for the [3 + 2] cycloaddition reactions between isocyanoacetates and
      cyclopentenediones. The current Ag(I) catalyst system tolerates moisture and air
      and readily utilizes class III solvents such as EtOAc and acetone. The
      development of on demand generation of an active chiral catalyst in the presence
      of isocyanides paves a way to the efficient asymmetric preparation of bicyclic
      pyrrolidines with four stereogenic centers, including two quaternary centers in
      80-97% ee.

PMID- 29583011
TI  - Bimolecular Master Equations for a Single and Multiple Potential Wells with
      Analytic Solutions.
AB  - The analytic solutions, that is, populations, are derived for the K-adiabatic and
      K-active bimolecular master equations, separately, for a single and multiple
      potential wells and reaction channels, where K is the component of the total
      angular momentum J along the axis of least moment of inertia of the recombination
      products at a given energy E. The analytic approach provides the functional
      dependence of the population of molecules on its K-active or K-adiabatic
      dissociation, association rate constants and the intermolecular energy transfer,
      where the approach may complement the usual numerical approaches for reactions of
      interest. Our previous work, Part I, considered the solutions for a single
      potential well, whereby an assumption utilized there is presently obviated in the
      derivation of the exact solutions and farther discussed. At the high-pressure
      limit, the K-adiabatic and K-active bimolecular master equations may each reduce,
      respectively, to the K-adiabatic and K-active bimolecular Rice-Ramsperger-Kassel
      Marcus theory (high-pressure limit expressions) for bimolecular recombination
      rate constant, for a single potential well, and augmented by isomerization terms
      when multiple potential wells are present. In the low-pressure limit, the
      expression for population above the dissociation limit, associated with a single
      potential well, becomes equivalent to the usual presumed detailed balance between
      the association and dissociation rate constants, where the multiple well case is
      also considered. When the collision frequency of energy transfer, ZLJ, between
      the chemical intermediate and bath gas is sufficiently less than the dissociation
      rate constant kd( E' J' K') for postcollision ( E' J' K), then the solution for
      population, g( EJK)+, above the critical energy further simplifies such that
      depending on ZLJ, the dissociation and association rate constant kr( EJK), as g(
      EJK)+ = kr( EJK)A.BC/[ ZLJ+ kd( EJK)], where A and BC are the reactants, for
      example, relevant for O3 formation from O + O2 + Ar up to ~100 bar; otherwise,
      additional contributions from postcollision are present and especially relevant
      at high pressures. In the aforementioned regime ZLJ < kd( E' J' K) the physical
      connection of recombination rate constants, krec based on either utilizing
      population from the master equation approach or a collision based bimolecular
      RRKM theory is traced and elucidated analytically that the rate constants are
      equal. Recombination rate constants, krec, based on the population, are also
      given and considered for an adiabatic or active K. For example, for O3 formation
      in Ar bath gas, the K-adiabatic-based krec for O3 yields 4.0 * 10-34 cm6 molecule
      2 s-1 at T = 300 K and 1 bar, in agreement with the experimental value, where the
      contribution from the population of metastable ozone is discussed and the
      adiabaticity of K highlighted. A facile numerical implementation of the formalism
      for g( EJK) and krec for O3 is noted. The application of the expressions to ozone
      recombination as a function of pressure and temperature is given elsewhere,
      beyond the selection considered here, for studying the physical features,
      including the contributions from the K and intermolecular energy transfer to the
      krec, and the puzzles reported from experiments for this reaction.

PMID- 29583012
TI  - Single-Photon Emitters in Boron Nitride Nanococoons.
AB  - Quantum emitters in two-dimensional hexagonal boron nitride (hBN) are attractive
      for a variety of quantum and photonic technologies because they combine ultra
      bright, room-temperature single-photon emission with an atomically thin crystal.
      However, the emitter's prominence is hindered by large, strain-induced wavelength
      shifts. We report the discovery of a visible-wavelength, single-photon emitter
      (SPE) in a zero-dimensional boron nitride allotrope (the boron nitride
      nanococoon, BNNC) that retains the excellent optical characteristics of few-layer
      hBN while possessing an emission line variation that is lower by a factor of 5
      than the hBN emitter. We determined the emission source to be the nanometer-size
      BNNC through the cross-correlation of optical confocal microscopy with high
      resolution scanning and transmission electron microscopy. Altogether, this
      discovery enlivens color centers in BN materials and, because of the BN
      nanococoon's size, opens new and exciting opportunities in nanophotonics, quantum
      information, biological imaging, and nanoscale sensing.

PMID- 29583013
TI  - Asymmetric Construction of Remote Vicinal Quaternary and Tertiary Stereocenters
      via Direct Doubly Vinylogous Michael Addition.
AB  - An asymmetric direct doubly vinylogous Michael addition has been developed for
      the generation of sterically congested vicinal quaternary and tertiary
      stereocenters. This doubly vinylogous Michael addition of beta,gamma-unsaturated
      butenolides to 3-methyl-4-nitro-5-alkenyl isoxazoles, powered by a bifunctional
      squaramide, affords a broad range of densely functionalized enantioenriched
      gamma,gamma-disubstituted butenolides in high yields with excellent diastereo-
      and enantioselectivities in most cases. Moreover, the strategy highlights the
      first application of beta,gamma-unsaturated butenolides in an asymmetric 1,6
      conjugate addition.

PMID- 29583014
TI  - Herbal Prescriptions and Medicinal Herbs for Parkinson-Related Rigidity in Korean
      Medicine: Identification of Candidates Using Text Mining.
AB  - BACKGROUND: Dongeuibogam (DongYiBaoGian), one of the most important books in
      Korean medicine, comprises a comprehensive summary of all traditional medicines
      of North-East Asia before the 17th century. This medicinal literature was mined
      to establish a list of candidate herbs to treat Parkinson-related rigidity.
      METHODS: A systematic search for terms describing Parkinson-related rigidity and
      candidate prescriptions for the treatment of Parkinson-related rigidity in the
      Dongeuibogam was performed. A high-frequency medicinal herb combination group and
      candidates for the treatment of Parkinson-related rigidity were also selected
      through an analysis of medicinal herb combination frequencies. The existing
      literature pertaining to the potential effects of candidate herbs for Parkinson
      related rigidity was reviewed. RESULTS AND CONCLUSIONS: Ten medicinal herb
      candidates for the treatment of Parkinson-related rigidity were selected, and
      their respective precedent studies were analyzed.

PMID- 29583016
TI  - Preliminary study of Novafon local vibration voice therapy for dysphonia
      treatment.
AB  - BACKGROUND: The objective of this study was to explore the effectiveness of a
      five-week Novafon local vibration voice therapy (NLVVT) program for dysphonia
      treatment. METHODS: Eleven dysphonic subjects participated in this specific
      program. RESULTS: Treatment effects were assessed during (i.e. weekly) and after
      NLVVT. Large and significant treatment effects were revealed in acoustics (i.e.
      spectrography), and multiparametric indices (i.e. Acoustic Voice Quality Index
      (AVQI), and Dysphonia Severity Index (DSI)) during and after NLVVT (all p values
      < .01). Additionally, self-evaluation (i.e. Voice Handicap Index (VHI)) showed a
      significant improvement after NLVVT (p < .01). Gender independent voice range
      profile parameters (i.e. acoustics) only showed significant effects after
      treatment (p <= .01), but not during the treatment. Finally, aerodynamic
      measurement (i.e. phonation quotient) showed low treatment effects after NLVVT,
      which were not significant (p > .05). CONCLUSIONS: The preliminary results showed
      that NLVVT might be successful in voice treatment. Large treatment effects might
      be expected in AVQI, DSI, spectrography and VHI after using NLVVT. Other voice
      characteristics showed smaller treatment effects (i.e. voice range profile
      parameters) or no meaningful treatment effects (i.e. phonation quotient).

PMID- 29583017
TI  - Identification and characterization of cis-regulatory elements 'insulator and
      repressor' in PPARD gene.
AB  - AIM: Identification and functional characterization of cis-regulatory elements in
      human PPARD gene. METHODS: We used various bioinformatic tools on the publicly
      available human genome and Encyclopedia of DNA Elements databases to explore
      potential cis-regulatory elements in PPARD gene region. RESULTS: We predicted an
      insulator and an enhancer element in intron 2 of PPARD gene. Functional
      characterization using transient transfection, reporter assay and CTCF binding
      confirmed the insulator status. However, the predicted enhancer element showed
      repressor/silencer activity. Finally, we observed a potential interaction between
      these two cis-regulatory elements which is in agreement with 5C-Encyclopedia of
      DNA Elements data. CONCLUSION: We report two functionally validated cis
      regulatory elements in PPARD gene which will aid in understanding its regulation
      and role in metabolic functions.

PMID- 29583018
TI  - How patient-selected colors for removable appliances are reflected in
      electronically tracked compliance (wear times and wear behavior).
AB  - OBJECTIVES: A broad spectrum of colors for removable appliances, intended to
      optimize acceptance of treatment and patient cooperation, have been available on
      the dental market for years. This is the first study to analyze how patient
      selected colors are reflected in wear times and wear behavior of removable
      appliances. MATERIALS AND METHODS: The study included 117 children (55 girls and
      62 boys) who were treated with active removable plate or functional appliances.
      All patients were offered to choose from 11 different colors, which were pooled
      into six groups (black, blue, green, yellow, pink, red) for analysis, or to
      combine any two to four colors ("multicolored" group) for their appliances. All
      appliances featured a built-in microsensor (TheraMon; MC Technology, Hargelsberg,
      Austria) for objective wear-time tracking. Differences between wear times were
      analyzed using pairwise t tests and Tukey correction. RESULTS: The longest median
      wear times were recorded in the blue and green groups (~11 h/d) and the shortest
      ones in the red and pink groups (~9 h/d), but they were not significantly
      influenced by the patient-selected colors. The median wear times involved an age
      related decrease by 0.56 h/y that was statistically significant ( P = .00005). No
      gender-specific patterns of wear behavior were observed. CONCLUSIONS: Patient
      selected colors for removable appliances can presumably improve acceptance of
      treatment, but they are not associated with statistically significant
      improvements in wear time or wear behavior.

PMID- 29583015
TI  - Effects of 90 Days of Resveratrol Supplementation on Cognitive Function in
      Elders: A Pilot Study.
AB  - OBJECTIVE: The purpose of this trial was to study the effects of chronic
      resveratrol use on cognitive function in humans. DESIGN: The authors conducted a
      double-blind, Phase IIa randomized, placebo-controlled trial to obtain
      preliminary estimates of the effects of resveratrol supplementation on cognitive
      function over a 90-day period in older adults. LOCATION: University of Florida in
      Gainesville, FL. SUBJECTS: Sedentary, overweight older adults (N = 32; age range:
      65-93 years, M age = 73.34 years, SD age = 7.02 years). INTERVENTION:
      Participants were randomized to one of three treatment groups (placebo, 300
      mg/day resveratrol, 1000 mg/day resveratrol) for 90 days. OUTCOME MEASURES:
      Cognitive function was assessed before and after treatment using a well
      characterized test battery: Trail Making, Digits Forward and Backward, Erikson
      Flanker, Controlled Oral Word Association, Hopkins Verbal Learning Test-Revised,
      and Task Switching. RESULTS: Psychomotor speed improved on the Trail Making Test
      part A in participants taking 1000 mg/day of resveratrol compared with
      participants in both the 300 mg/day condition and the placebo condition (p =
      0.02). CONCLUSION: This pilot study suggests that 90 days of resveratrol
      supplementation at a dose of 1000/mg per day selectively improves psychomotor
      speed but does not significantly affect other domains of cognitive function in
      older adults. These findings provide modest support to further study the effects
      of resveratrol on cognitive function in older adults.

PMID- 29583019
TI  - Vaginal progesterone and the vaginal first-pass effect.
AB  - Vaginal progesterone is an effective alternative to systemic administration by
      oral or intramuscular use. The first-pass effect is reviewed, as are the most
      common uses for this route of delivery. This includes use in hormone replacement
      therapy, luteal support particularly in assisted reproduction, and avoidance of
      side-effects of oral progestins and progesterone. Vaginal progesterone represents
      a unique therapeutic solution to a number of clinical problems.

PMID- 29583020
TI  - Interventional Pulmonology-Bridging the Gaps through Standardization: Malignant
      Pleural Effusion, Mediastinal Staging, and Cryobiopsy.

PMID- 29583021
TI  - COPD 2017: A Year in Review.
AB  - In this review, we focused on original manuscripts published in the 2017 that
      provided additional information on the clinical and therapeutic features of the
      chronic obstructive pulmonary disease (COPD). We have chosen eight of these
      studies, collected in four topics concerning the pharmacological treatment
      (tiotropium) of mild-moderate patients, the pharmacological (fluticasone
      furoate/vilanterol/umeclidinium) and non-pharmacological treatment (non-invasive
      mechanical ventilation) of severe patients, the etiology of acute exacerbation of
      COPD involving seasonal airway pathogens and the role of eosinophils with
      particular interest to the monoclonal antibody directed against interleukin-5
      (mepolizumab). For each topic, we report a brief description of studies, take
      home messages, and brief comments.

PMID- 29583022
TI  - Provider Information Provision and Breast Cancer Patient Well-Being.
AB  - Research continues to delineate and clarify specific communication behaviors
      associated with improved patient outcomes. In the context of breast cancer
      surgery, this exploratory study examined the effect of breast surgeon information
      provision on the immediate post-visit outcomes of patients' anxious
      preoccupation, intention to adhere to treatment recommendations, and treatment
      plan satisfaction. Participants included 51 newly diagnosed breast cancer
      patients receiving care from one breast surgeon at a National Cancer Institute
      designated cancer center in the northeastern United States. Participants
      completed pre- and post-visit questionnaires. Medical interactions were recorded,
      transcribed, and analyzed via multidimensional analysis, a method of linguistic
      analysis that uses exploratory factor analysis to identify how specific types of
      words are patterned and work to accomplish communicative goals (Biber, 1988). The
      multidimensional analysis identified constellations of language used by providers
      and patients. Although five linguistic dimensions emerged, one dimension,
      impersonal information provision, is of unique interest in understanding how
      providers communicate with patients. Impersonal information provision encompasses
      the ways in which the provider, using an impersonal tone, discussed the
      logistics, details, and implications of treatment options. Increased impersonal
      information provision was associated with patients' decreased anxious
      preoccupation (beta = -.22, t = -2.82, p = .007), increased treatment plan
      satisfaction (beta = .36, t = 2.54, p = .012), and increased intention to adhere
      to treatment recommendations (beta = .34, t = 2.45, p = .018). Findings suggest
      that specific provider behavior and types of information provided have unique and
      important effects on patients' health outcomes.

PMID- 29583024
TI  - Professor John Delos DeLamater (1940-2017).

PMID- 29583023
TI  - A viable caesarean scar pregnancy in a woman using a levonorgestrel-releasing
      intrauterine device: a case report.
AB  - BACKGROUND: Although the levonorgestrel-releasing intrauterine device (LNG-IUD)
      is one of the most reliable methods of contraception, it is associated with an
      increased risk of ectopic pregnancy in case of unintended pregnancy. A rare form
      of ectopic pregnancy is the caesarean scar pregnancy (CSP), with a high risk of
      serious maternal morbidity, such as uterine rupture, massive haemorrhage and
      resulting infertility. This report describes the first case of a viable CSP at 13
      weeks of gestation in association with the use of a LNG-IUD. Case-presentation: A
      36-year-old Caucasian woman was referred to our outpatient clinic because of
      suspicion of a CSP. The pregnancy was unintended and was diagnosed during
      replacement of the LNG-IUD after five years. The patient had undergone two
      caesarean sections in the past. Ultrasound investigation showed an intact
      pregnancy of approximately 13 weeks of gestation located in the uterine scar.
      Because of the size of the gestational sac, a laparotomy was performed under
      general anaesthesia using a Joel-Cohen incision. The procedure was complicated by
      a total blood loss of 1500 mL, mostly caused by diffuse bleeding from the
      placental bed. CONCLUSION: Unintended pregnancies in women using a LNG-IUD are
      frequently ectopic pregnancies with a preponderance to nidate outside the
      fallopian tube. Therefore, early diagnosis and location of the pregnancy in women
      using a LNG-IUD is essential.

PMID- 29583025
TI  - Disgust Toward Sex-Relevant and Sex-Irrelevant Stimuli in Pre-, Early, and Middle
      Adolescence.
AB  - For prepubertal youth, sexual stimuli elicit disgust and avoidance, yet in
      adolescence this avoidance shifts to sexual approach. One explanation could be
      that disgust declines in adolescence. This project examined whether disgust is
      indeed lower in adolescence compared to preadolescence, and whether this
      difference across age groups would be restricted to sex-relevant disgust
      elicitors. We also examined whether the strength of disgust would depend on
      familiarity between participant and source. To examine disgust responses in
      youths, two cross-sectional studies (N = 248, ages six to 17 years) were
      conducted using scenario-based measurements. Disgust was overall higher in early
      adolescence than in preadolescence and relatively weak when the source of disgust
      was a familiar person. Specifically, when parents were the source, sex-relevant
      disgust was higher in the groups of early and middle adolescents than in the
      group of preadolescents. Sex-relevant disgust elicited by a stranger or best
      friend, however, was lower in middle than in early adolescence. The latter is
      consistent with the view that repeated confrontation with disgusting stimuli
      might attenuate disgust, which could contribute to healthy sexual functioning.
      The heightened sex-relevant disgust in middle adolescents when parents were the
      source might reflect a functional avoidance mechanism of inappropriate sex mates.

PMID- 29583026
TI  - A new method of onset and offset detection in ensemble singing.
AB  - This paper presents a novel method combining electrolaryngography and acoustic
      analysis to detect the onset and offset of phonation as well as the beginning and
      ending of notes within a sung legato phrase, through the application of a peak
      picking algorithm, TIMEX. The evaluation of the method applied to a set of
      singing duo recordings shows an overall performance of 78% within a tolerance
      window of 50 ms compared with manual annotations performed by three experts.
      Results seem very promising in light of the state-of-the-art techniques presented
      at MIREX in 2016 yielding an overall performance of around 60%. The new method
      was applied to a pilot study with two duets to analyse synchronization between
      singers during ensemble performances. Results from this investigation demonstrate
      bidirectional temporal adaptations between performers, and suggest that the
      precision and consistency of synchronization, and the tendency to precede or lag
      a co-performer might be affected by visual contact between singers and leader
      follower relationships. The outcomes of this paper promise to be beneficial for
      future investigations of synchronization in singing ensembles.

PMID- 29583028
TI  - Progesterone, progestins and the endometrium in perimenopause and in menopausal
      hormone therapy.
AB  - It is well established that unopposed estrogen for hormone therapy in
      postmenopausal women (MHT) induces a dose-related stimulation of the endometrium
      associated with an increased risk of hyperplasia and endometrial cancer.
      Progesterone acts physiologically to counteract the proliferative effects of
      estradiol during the menstrual cycle. In MHT, progestogens protect the
      endometrium against the proliferative effects of estrogens in women with a
      uterus. Recent data suggest that, whereas micronized progesterone is apparently
      safer for the breast, it could be less efficient than synthetic progestin on the
      endometrium. An update on progestogen and endometrial safety in MHT is the
      subject of this review.

PMID- 29583027
TI  - Enhancer talk.
AB  - Enhancers are short noncoding segments of DNA (100-1000 bp) that control the
      temporal and spatial activity of genes in an orientation-independent manner. They
      can be separated from their target genes by large distances and are thus known as
      distal regulatory elements. One consequence of the variability in the distance
      separating enhancers and their target promoters is that it is difficult to
      determine which elements are involved in the regulation of a particular gene.
      Moreover, enhancers can be found in clusters in which multiple regulatory
      elements control expression of the same target gene. However, little is known
      about how the individual elements contribute to gene expression. Here, we
      describe how chromatin conformation promotes and constraints enhancer activity.
      Further, we discuss enhancer clusters and what is known about the contribution of
      individual elements to the regulation of target genes. Finally, we examine the
      reliability of different methods used to identify enhancers.

PMID- 29583029
TI  - Bacterial detection using bacteriophages and gold nanorods by following time
      dependent changes in Raman spectral signals.
AB  - This study attemps to develop bacterial detection strategies using bacteriophages
      and gold nanorods (GNRs) by Raman spectral analysis. Escherichia coli was
      selected as the target and its specific phage was used as the bioprobe. Target
      bacteria and phages were propagated/purified by traditional techniques. GNRs were
      synthesized by using hexadecyltrimethyl ammonium bromide (CTAB) as stabilizer. A
      two-step detection strategy was applied: Firstly, the target bacteria were
      interacted with GNRs in suspensions, and then they were dropped onto silica
      substrates for detection. It was possible to obtain clear surface-enchanced Raman
      spectroscopy (SERS) peaks of the target bacteria, even without using phages. In
      the second step, the phage nanoemulsions were droped onto the bacterial-GNRs
      complexes on those surfaces and time-dependent changes in the Raman spectra were
      monitored at different time intervals upto 40 min. These results demonstrated
      that how one can apply phages with plasmonic nanoparticles for detection of
      pathogenic bacteria very effectively in a quite simple test.

PMID- 29583032
TI  - Evaluation of natural mandibular shape asymmetry: an approach by using elliptical
      Fourier analysis.
AB  - OBJECTIVES: The purpose of this study was to demonstrate that asymmetry is a
      natural occurring phenomenon in the mandibular shape by using elliptical Fourier
      analysis. METHODS: 164 digital orthopantomographs from Colombian patients of both
      sexes aged 18 to 25 years were collected. Curves from left and right hemimandible
      were digitized. An elliptical Fourier analysis was performed with 20 harmonics.
      In the general sexual dimorphism a principal component analysis (PCA) and a
      hotelling T2 from the multivariate warp space were employed. Exploratory analysis
      of general asymmetry and sexual dimorphism by side was made with a Procrustes
      Fit. A non-parametric multivariate analysis of variance (MANOVA) was applied to
      assess differentiation of skeletal classes of each hemimandible, and a Procrustes
      analysis of variance (ANOVA) was applied to search any relation between skeletal
      class and side in both sexes. RESULTS: Significant values were found in general
      asymmetry, general sexual dimorphism, in dimorphism by side (p < 0.0001),
      asymmetry by sex, and differences between Class I, II, and III (p < 0.005).
      However, a relation of skeletal classes and side was not found. CONCLUSIONS: The
      mandibular asymmetry by shape is present in all patients and should not be
      articulated exclusively to pathological processes, therefore, along with sexual
      dimorphism and differences between skeletal classes must be taken into account
      for improving mandibular prediction systems.

PMID- 29583031
TI  - The 2018 Lake Louise Acute Mountain Sickness Score.
AB  - Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bartsch, Andrew M. Luks,
      Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus
      Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol
      19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has
      been a useful research tool since first published in 1991. Recent studies have
      shown that disturbed sleep at altitude, one of the five symptoms scored for AMS,
      is more likely due to altitude hypoxia per se, and is not closely related to AMS.
      To address this issue, and also to evaluate the Lake Louise AMS score in light of
      decades of experience, experts in high altitude research undertook to revise the
      score. We here present an international consensus statement resulting from online
      discussions and meetings at the International Society of Mountain Medicine World
      Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia
      Symposium in Lake Louise, Canada, in February 2015. The consensus group has
      revised the score to eliminate disturbed sleep as a questionnaire item, and has
      updated instructions for use of the score.

PMID- 29583033
TI  - Adult self-image and well-being after testicular cancer: The role of agency and
      meaning.
AB  - OBJECTIVE: Cancer during young adulthood can limit the extent to which one adopts
      an adult self-image. However, the relationship of adult self-image to cancer
      related adjustment remains unexplored. The current study examines relationships
      of adult self-image and social/emotional well-being and job-related problems in
      young testicular cancer survivors. Factors thought to facilitate future-oriented
      goals (i.e. agency and meaning) are examined as intermediary processes. DESIGN:
      Testicular cancer survivors (N = 171) between the ages of 18 and 29 completed
      questionnaire measures of adult self-image, agency, sense of meaning and
      indicators of adjustment. MAIN OUTCOME MEASURES: Social and emotional well-being
      were measured by the Functional Assessment of Cancer Therapy-General. Job
      problems were assessed using the EORTC's testicular cancer supplement (EORTC QLQ
      TC26). RESULTS: Path model results revealed direct associations of survivors'
      adult self-image with social (beta = .20, p < .05), but not emotional well-being
      (beta = .14, p < .01). Both agency and meaning mediated the relationship of adult
      self-image and well-being indicators. Finally, the relationship between adult
      self-image and job problems was only significant for those who were employed or
      in school (beta = -.19, p < .05). OUTCOMES: Assessment of adult self-image might
      be useful in identifying risk for poor adjustment. Interventions that target
      agency and meaning might facilitate developmental goals.

PMID- 29583030
TI  - SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate
      immunity.
AB  - Sterile alpha motif and histidine-aspartic acid domain-containing protein 1
      (SAMHD1) is a deoxynucleotide triphosphate (dNTP) hydrolase that plays an
      important role in the homeostatic balance of cellular dNTPs. Its emerging role as
      an effector of innate immunity is affirmed by mutations in the SAMHD1 gene that
      cause the severe autoimmune disease, Aicardi-Goutieres syndrome (AGS) and that
      are linked to cancer. Additionally, SAMHD1 functions as a restriction factor for
      retroviruses, such as HIV. Here, we review the current biochemical and biological
      properties of the enzyme including its structure, activity, and regulation by
      post-translational modifications in the context of its cellular function. We
      outline open questions regarding the biology of SAMHD1 whose answers will be
      important for understanding its function as a regulator of cell cycle
      progression, genomic integrity, and in autoimmunity.

PMID- 29583034
TI  - Becoming active: more to exercise than weight loss for indigenous men.
AB  - OBJECTIVE: To understand what motivates sedentary indigenous and ethnic minority
      men to become more physically active. DESIGN: We use thematic analysis to present
      data from a qualitative study exploring 23 sedentary indigenous Maori (New
      Zealand) men's experiences of completing a 12-week exercise intervention to
      improve their metabolic health. RESULTS: Four themes emerged: The Bros - having
      fellowship and mutual motivation; Being better informed about exercise; Impacting
      overall wellbeing; and Disseminating the findings beyond the study Exercise
      interventions informed by indigenous Maori cultural values and knowledge
      increased its relevance to their daily lives. The motivation for these indigenous
      men was more culturally-based external factors than an inherent desire to lose
      weight. CONCLUSION: Indigenous and minority men in many developed countries have
      high morbidity and premature mortality related to sedentary lifestyles. The low
      uptake of physical activities possibly relates to focusing more on outcomes such
      as weight loss which lacks cultural relevance. When offering health promotion
      interventions for marginalized populations these findings highlight the
      importance of culturally tailoring interventions to the unique sources of
      motivation for each group to increase activity to improve their efficacy.

PMID- 29583035
TI  - A long-term follow-up study of men born with very low birth weight and their
      reproductive hormone profile.
AB  - : Environmental factors during the fetal period may adversely affect reproductive
      functions in men being born with very low birth weight (VLBW, <1500 g). The
      objective of this prospective, controlled cohort study was to investigate if VLBW
      men have an altered reproductive hormone profile compared with men born at term.
      The study group initially consisted of all VLBW boys live-born between 1 February
      1987 and 30 April 1988 in the south-east region of Sweden (n = 47). A control
      child was chosen born at term, at the same hospital, with the same parity,
      without malformations, and next in order after each VLBW child who survived the
      first four weeks (n = 45). The present follow-up was performed when the men were
      26-28 years of age and included measurements of serum hormone levels, hair
      testosterone concentration, and anthropometric data. Also life-style
      questionnaires were collected from 26 VLBW men and 19 controls. The VLBW group (n
      = 26) had higher median levels of serum estradiol, 84.5 pmol/L than controls (n =
      19), 57.5 pmol/L (p = 0.008). There was no significant correlation between serum
      estradiol and BMI (r = 0.06, p = 0.74). There were no differences in other
      hormone levels or the reproductive pattern between the groups. In conclusion,
      even though there was a statistically significant difference in estradiol levels
      between the groups, both groups had low normal mean levels of questionable
      clinical significance. The reproductive pattern was similar in the two groups and
      in this study being born VLBW does not seem to affect these measured aspects of
      reproduction. ABBREVIATIONS: ADHD: attention deficit hyperactive disorder; AGA:
      average for gestational age; BMI: body mass index; CP: cerebral palsy; DHT:
      dihydrotestosterone; FSH: follicle stimulating hormone; LBW: low birth weight;
      LH: luteinizing hormone; SAD: sagittal abdominal diameter; SGA: small for
      gestational age; SHBG: sex hormone binding globulin; TSH: thyroid stimulating
      hormone; T3: triiodothyronine; T4: thyroxin; VLBW: very low birth weight.

PMID- 29583036
TI  - The ocular involvement did not accompany with the genital ulcer or the
      gastrointestinal symptoms at the early stage of Behcet's disease.
AB  - OBJECTIVES: This study aimed to identify patients with high-probability of ocular
      involvement of Behcet's disease (BD). METHODS: The Japanese Ministry of Health,
      Labour and Welfare provided dataset of ongoing nationwide BD registration
      project. A patient who had confirmed BD and who was suspected to have BD was
      registered. We mainly analyzed newly registered patients who had the data for all
      demographic and diagnostic parameters regardless of fulfilment of any diagnostic
      criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382
      (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years
      (interquartile range (IQR) 30-49 years). The median duration between onset and
      registration was 0 year (IQR 0-3). A binomial multivariable logistic regression
      analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence
      interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years,
      95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p <
      .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were
      related to the ocular lesion. Analyses based on data of 2800 patients who
      satisfied International criteria of BD, age-, sex-, duration-based subgroup
      analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis
      including patients with missing data confirmed that the four factors were
      associated with the probability of eye involvement. CONCLUSION: The ocular
      involvement did not accompany with genital ulcer or gastrointestinal symptoms at
      the early stage of BD.

PMID- 29583037
TI  - Detection of atrial fibrillation during pulpal blood flow assessment using
      Doppler ultrasound: a case report.
AB  - This report describes the case of a 52-year-old male patient who exhibited
      suspicious pulsation patterns during pulpal blood flow assessment using Doppler
      ultrasound. Initially, he was not aware of his cardiovascular problem; however,
      after referral to a medical clinic, he was diagnosed with atrial fibrillation.
      The patient was injured in a motor vehicle accident and referred to our clinic
      for management of multiple traumatized teeth. On clinical examination, several
      teeth exhibited negative responses to cold and electrical sensibility tests. For
      accurate diagnosis, pulpal blood flow assessment using a Doppler ultrasound
      device was performed. During the tests, irregular pulsation patterns were
      detected, indicating the possibility of a cardiovascular problem. As he denied
      any history of cardiovascular problems, he was recommended to visit a medical
      doctor for further evaluation. The following day, he visited a medical clinic,
      and a 12-lead electrocardiogram was performed. He was ultimately diagnosed with
      atrial fibrillation with idioventricular rhythm, and was started on anticoagulant
      medication for prevention of thrombogenesis, which is a possible complication of
      atrial fibrillation. As presented in this case, Doppler ultrasound can provide
      useful information, not only about blood flow in the dental pulp, but also about
      an individual's pulsation rhythm. When a patient presents with irregular
      pulsation patterns in certain situations, the possibility of cardiovascular
      problems should be considered.

PMID- 29583038
TI  - Dishevelled 1, a pivotal positive regulator of the Wnt signalling pathway,
      mediates 5-fluorouracil resistance in HepG2 cells.
AB  - Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with
      hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are
      poorly understood. The aim of this study was to identify candidate genes and
      associated signalling pathways that may play a role in developing drug resistance
      following repeated 5-FU treatments. In this work, we established 5-FU-resistant
      cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental
      HepG2 cells. Using transcriptome sequencing, we found that the expressions of the
      Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and
      APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated
      and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt
      signalling. Dishevelled-1 (DVL1) is an essential Wnt signalling pathway component
      that stabilizes beta-catenin and mediates the Wnt pathway. Silencing DVL1 using
      siDVL1 or other small molecular inhibitors in HepG2/5-FU cells could restore 5-FU
      responsiveness via reduced cell proliferation and migration, and increased
      apoptosis. Moreover, DVL1 was found to be upregulated in BEL-7402/5-FU cells when
      compared to the parental BEL-7402 cells. Collectively, our results provide the
      first clue towards understanding the contribution of DVL1-mediated acquired
      resistance to 5-FU in HepG2/5-FU cells, suggesting a promising therapeutic
      strategy for liver cancer resistant to 5-FU.

PMID- 29583039
TI  - Use of proteomic analysis to determine the protein constituents of synovial fluid
      samples from the stifle joints of dogs with and without osteoarthritis secondary
      to cranial cruciate ligament rupture.
AB  - OBJECTIVE To use proteomic analysis to determine the protein constituents of
      synovial fluid samples from the stifle joints of dogs with and without
      osteoarthritis secondary to cranial cruciate ligament rupture (CCLR). ANIMALS 12
      dogs with clinically normal stifle joints (controls) and 16 dogs with
      osteoarthritis secondary to CCLR. PROCEDURES A synovial fluid sample was obtained
      from all dogs. Synovial fluid total protein concentration was determined by the
      Bradford assay. Proteins were separated by use of a 1-D SDS-PAGE to detect
      protein bands that differed between dogs with and without osteoarthritis. Those
      protein bands then underwent trypsin digestion and were analyzed by matrix
      assisted laser desorption-ionization time-of-flight mass spectrometry, the
      results of which were compared with a curated protein sequence database for
      protein identification. One of the most frequently identified proteins,
      apoprotein (apo) A-I, was then quantified in all synovial fluid samples by use of
      a competitive-inhibition ELISA. Results were compared between dogs with and
      without osteoarthritis. RESULTS Median synovial fluid total protein and apo A-I
      concentrations for dogs with osteoarthritis were significantly greater than those
      for control dogs. The most abundant proteins identified in the synovial fluid
      were albumin and apo A-I. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated
      that quantification of synovial fluid total protein and apo A-I concentrations
      might facilitate diagnosis of osteoarthritis secondary to CCLR in dogs. Further
      research and validation of synovial fluid apo A-I concentration as a biomarker
      for osteoarthritis in dogs are necessary before it can be recommended for
      clinical use.

PMID- 29583040
TI  - Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory
      and gastrointestinal changes induced by detomidine hydrochloride in horses.
AB  - OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on
      detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes
      in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine
      hydrochloride (20 MUg/kg, IV), followed 10 minutes later by MK-467 hydrochloride
      (150 MUg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9%
      NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory
      rate, rectal temperature, arterial and venous blood pressures, and cardiac output
      were measured; blood gases and arterial plasma drug concentrations were analyzed;
      selected cardiopulmonary variables were calculated; and sedation and
      gastrointestinal borborygmi were scored at predetermined time points. Differences
      among treatments or within treatments over time were analyzed statistically.
      RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were
      reversed shortly after MK-467 injection. Marked tachycardia and hypertension were
      observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed
      significantly among all treatments from 15 to 35 and 15 to 40 minutes after
      detomidine injection, respectively. Cardiac output was greater with DET-MK and
      DET-HYO than with DET-S 15 minutes after detomidine injection, but left
      ventricular workload was significantly higher with DET-HYO. Borborygmus score,
      reduced with all treatments, was most rapidly restored with DET-MK. Sedation
      scores and pharmacokinetic parameters of detomidine did not differ between DET-S
      and DET-MK. CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated
      cardiovascular and gastrointestinal effects of detomidine without notable adverse
      effects or alterations in detomidine-induced sedation in horses. Further research
      is needed to determine whether these advantages are found in clinical patients
      and to assess whether the drug influences analgesic effects of detomidine.

PMID- 29583042
TI  - Torsional and axial compressive properties of tibiotarsal bones of red-tailed
      hawks (Buteo jamaicensis).
AB  - OBJECTIVE To describe the torsional and axial compressive properties of
      tibiotarsal bones of red-tailed hawks (Buteo jamaicensis). SAMPLE 16 cadaveric
      tibiotarsal bones from 8 red-tailed hawks. PROCEDURES 1 tibiotarsal bone from
      each bird was randomly assigned to be tested in torsion, and the contralateral
      bone was tested in axial compression. Intact bones were monotonically loaded in
      either torsion (n = 8) or axial compression (8) to failure. Mechanical variables
      were derived from load-deformation curves. Fracture configurations were
      described. Effects of sex, limb side, and bone dimensions on mechanical
      properties were assessed with a mixed-model ANOVA. Correlations between
      equivalent torsional and compressive properties were determined. RESULTS Limb
      side and bone dimensions were not associated with any mechanical property. During
      compression tests, mean ultimate cumulative energy and postyield energy for
      female bones were significantly greater than those for male bones. All 8 bones
      developed a spiral diaphyseal fracture and a metaphyseal fissure or fracture
      during torsional tests. During compression tests, all bones developed a crushed
      metaphysis and a fissure or comminuted fracture of the diaphysis. Positive
      correlations were apparent between most yield and ultimate torsional and
      compressive properties. CONCLUSIONS AND CLINICAL RELEVANCE The torsional and
      axial compressive properties of tibiotarsal bones described in this study can be
      used as a reference for investigations into fixation methods for tibiotarsal
      fractures in red-tailed hawks. Although the comminuted and spiral diaphyseal
      fractures induced in this study were consistent with those observed in clinical
      practice, the metaphyseal disruption observed was not and warrants further
      research.

PMID- 29583043
TI  - Effect of oral administration of robenacoxib on inhibition of paracentesis
      induced blood-aqueous barrier breakdown in healthy cats.
AB  - OBJECTIVE To determine the effect of oral administration of robenacoxib on
      inhibition of anterior chamber paracentesis (ACP)-induced breakdown of the blood
      aqueous barrier (BAB) and assess whether robenacoxib can cross an intact BAB in
      healthy cats. ANIMALS 12 healthy adult domestic shorthair cats. PROCEDURES Cats
      received robenacoxib (6-mg tablet in a treat, PO; n = 6) or a control treatment
      (treat without any drug, PO; 6) once daily for 3 days, beginning 1 day before
      ACP. One eye of each cat served as an untreated control, whereas the other
      underwent ACP, during which a 30-gauge needle was used to aspirate 100 MUL of
      aqueous humor for determination of robenacoxib concentration. Both eyes of each
      cat underwent anterior chamber fluorophotometry at 0 (immediately before), 6, 24,
      and 48 hours after ACP. Fluorescein concentration and percentage fluorescein
      increase were used to assess extent of ACP-induced BAB breakdown and compared
      between cats that did and did not receive robenacoxib. RESULTS Extent of BAB
      breakdown induced by ACP did not differ significantly between cats that did and
      did not receive robenacoxib. Low concentrations of robenacoxib were detected in
      the aqueous humor (mean, 5.32 ng/mL; range, 0.9 to 16 ng/mL) for 5 of the 6 cats
      that received the drug. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that
      oral administration of robenacoxib did not significantly decrease extent of BAB
      breakdown in healthy cats. Detection of low robenacoxib concentrations in the
      aqueous humor for most treated cats indicated that the drug can cross an intact
      BAB.

PMID- 29583044
TI  - Gross and histologic evaluation of effects of photobiomodulation, silver
      sulfadiazine, and a topical antimicrobial product on experimentally induced full
      thickness skin wounds in green iguanas (Iguana iguana).
AB  - OBJECTIVE To assess effects of photobiomodulation, silver sulfadiazine, and a
      topical antimicrobial product for the treatment of experimentally induced full
      thickness skin wounds in green iguanas (Iguana iguana). ANIMALS 16 healthy
      subadult green iguanas. PROCEDURES Iguanas were anesthetized, and three 5-mm
      cutaneous biopsy specimens were obtained from each iguana (day 0). Iguanas were
      randomly assigned to 2 treatment groups, each of which had a control treatment.
      Wounds in the topical treatment group received silver sulfadiazine, a topical
      antimicrobial product, or no treatment. Wounds in the laser treatment group
      received treatment with a class 4 laser at 5 or 10 J/cm2 or no treatment. Wound
      measurements were obtained daily for 14 days. Iguanas were euthanized, and
      treatment sites were evaluated microscopically to detect ulceration, bacterial
      contamination, reepithelialization, necrosis, inflammation, fibrosis, and
      collagen maturity. RESULTS On day 14, wounds treated with a laser at 10 J/cm2
      were significantly smaller than those treated with silver sulfadiazine, but there
      were no other significant differences among treatments. Histologically, there
      were no significant differences in ulceration, bacterial infection,
      reepithelialization, necrosis, inflammation, fibrosis, and collagen maturity
      among treatments. CONCLUSIONS AND CLINICAL RELEVANCE Photobiomodulation at 10
      J/cm2 appeared to be a safe treatment that was tolerated well by green iguanas,
      but it did not result in substantial improvement in histologic evidence of wound
      healing, compared with results for other treatments or no treatment.

PMID- 29583045
TI  - Effects of short-term anti-inflammatory glucocorticoid treatment on
      clinicopathologic, echocardiographic, and hemodynamic variables in systemically
      healthy dogs.
AB  - OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally
      administered intermediate-acting glucocorticoids (prednisone) could predispose
      dogs to progression of heart disease or congestive heart failure. ANIMALS 11
      client-owned dogs with allergic dermatitis and 11 matched healthy control dogs.
      PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were
      measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO)
      once daily for 14 consecutive days beginning on day 0 (baseline), followed by a
      tapering and washout period; control dogs received no treatment. Measurements
      were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare
      changes in variables across measurement points and between dog groups. RESULTS
      Prednisone administration caused no significant changes in serum sodium or
      potassium concentration, blood glucose concentration, or target echocardiographic
      variables. The change from baseline in systolic arterial blood pressure at day 7
      was significantly greater in prednisone-treated dogs than in control dogs.
      Expected changes in hematologic and serum biochemical values with prednisone
      administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline
      phosphatase and alanine aminotransferase activities) also occurred in the
      prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested
      that anti-inflammatory doses of orally administered glucocorticoids have the
      potential to adversely impact cardiac function in dogs by causing an increase in
      blood pressure and thus increased cardiac afterload.

PMID- 29583046
TI  - Quantitative analysis of brain perfusion parameters in dogs with idiopathic
      epilepsy by use of magnetic resonance imaging.
AB  - OBJECTIVE To quantitatively analyze brain perfusion parameters in dogs with
      idiopathic epilepsy (IE) by use of MRI and to compare those findings with brain
      perfusion parameters for healthy dogs. ANIMALS 12 client-owned dogs with IE.
      PROCEDURES For each dog, standard MRI and perfusion-weighted imaging (before and
      after injection of gadoteric acid contrast medium) sequences of the brain were
      obtained during the interictal period by means of the same protocol used in a
      comparable study of healthy dogs. Time of contrast medium arrival, time to peak
      contrast enhancement, mean contrast transit time, and cerebral blood flow were
      calculated for the caudate nucleus, thalamus, piriform lobe, hippocampus,
      semioval center, and temporal cerebral cortex. Parameters for each structure were
      compared between dogs with IE and healthy dogs. RESULTS Dogs with IE had a
      significantly greater mean time of contrast arrival and lower mean cerebral blood
      flow than healthy dogs. Differences in cerebral blood flow between dogs with IE
      and healthy dogs were most pronounced in the piriform lobe, thalamus, and
      temporal cerebral cortex. The mean contrast transit time did not differ between
      dogs with IE and healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results
      suggested that, compared with healthy dogs, dogs with IE have decreased blood
      perfusion of the brain. Findings of this study can be used as a basis for further
      research into functional changes within the brains of epileptic dogs during the
      interictal phase.

PMID- 29583047
TI  - Phagocytosis, bacterial killing, and cytokine activation of circulating blood
      neutrophils in horses with severe equine asthma and control horses.
AB  - OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of
      circulating blood neutrophils in horses with severe equine asthma and control
      horses and to determine whether circulating blood neutrophils in horses with
      severe equine asthma have an increase in expression of the proinflammatory
      cytokine tumor necrosis factor (TNF)-alpha and the chemokine interleukin (IL)-8
      and a decrease in expression of the anti-inflammatory cytokine IL-10 in response
      to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses.
      PROCEDURES Circulating blood neutrophils were isolated from horses with severe
      equine asthma and control horses. Phagocytosis was evaluated by use of flow
      cytometry. Bactericidal activity of circulating blood neutrophils was assessed by
      use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the
      cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS
      Circulating blood neutrophils from horses with severe equine asthma had
      significantly lower bactericidal activity toward S zooepidemicus but not toward S
      equi, compared with results for control horses. Phagocytosis and mRNA expression
      of TNF-alpha, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND
      CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood
      neutrophils in horses with severe equine asthma could contribute to an increased
      susceptibility to infections.

PMID- 29583048
TI  - Pharmacokinetics and pharmacodynamics after oral administration of tapentadol
      hydrochloride in dogs.
AB  - OBJECTIVE To evaluate pharmacokinetic and pharmacodynamic characteristics of 3
      doses of tapentadol hydrochloride orally administered in dogs. ANIMALS 6 healthy
      adult mixed-breed dogs. PROCEDURES In a prospective, randomized crossover study,
      dogs were assigned to receive each of 3 doses of tapentadol (10, 20, and 30
      mg/kg, PO); there was a 1-week washout period between subsequent administrations.
      Plasma concentrations and physiologic variables were measured for 24 hours.
      Samples were analyzed by use of high-performance liquid chromatography-tandem
      mass spectrometry. RESULTS Tapentadol was rapidly absorbed after oral
      administration. Mean maximum plasma concentrations after 10, 20, and 30 mg/kg
      were 10.2, 19.7, and 31 ng/mL, respectively. Geometric mean plasma half-life of
      the terminal phase after tapentadol administration at 10, 20, and 30 mg/kg was
      3.5 hours (range, 2.7 to 4.5 hours), 3.7 hours (range, 3.1 to 4.0 hours), and 3.7
      hours (range, 2.8 to 6.5 hours), respectively. Tapentadol and its 3 quantified
      metabolites (tapentadol sulfate, tapentadol-O-glucuronide, and
      desmethyltapentadol) were detected in all dogs and constituted 0.16%, 2.8%, 97%,
      and 0.04% of the total area under the concentration-time curve (AUC),
      respectively. Plasma AUCs for tapentadol, tapentadol sulfate, and tapentadol-O
      glucuronide increased in a dose-dependent manner. Desmethyltapentadol AUC did not
      increase in a linear manner at the 30-mg/kg dose. Sedation scores and heart and
      respiratory rates were not significantly affected by dose or time after
      administration. CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of
      tapentadol was tolerated well, and the drug was rapidly absorbed. Adverse events
      were not apparent in any dogs at any doses in this study.

PMID- 29583049
TI  - Role of toll-like receptor 4 and caspase-3, -8, and -9 in lipopolysaccharide
      induced delay of apoptosis in equine neutrophils.
AB  - OBJECTIVE To evaluate the effect of lipopolysaccharide (LPS) on apoptosis of
      equine neutrophils in vitro. SAMPLE Venous blood samples from 40 adult horses.
      PROCEDURES Neutrophils were isolated from blood samples and cultured with or
      without LPS from Escherichia coli O55:B5 for 12 or 24 hours. Neutrophil apoptosis
      was assessed by use of cytologic examination, annexin V and propidium iodide
      staining quantified with flow cytometry, coincubation with inducers of intrinsic
      and extrinsic apoptosis or a toll-like receptor (TLR) 4 inhibitor, and
      measurement of caspase-3, -8, and -9 activities. RESULTS Treatment with LPS
      resulted in a significant delay in apoptosis after incubation for 12 and 24 hours
      (neutrophils from blood samples of 40 horses). There was a significant
      correlation between increases in LPS dose and decreases in apoptosis after
      incubation for 24 hours (3 experiments, each of which involved neutrophils
      obtained from the same 3 horses at 3 separate times). Caspase-9 activity, but not
      caspase-3 or -8 activity, was significantly reduced in LPS-treated neutrophils
      after incubation for 12 hours (neutrophils from blood samples of 17 horses).
      Treatment with a TLR4 inhibitor or intrinsic and extrinsic inducers of apoptosis
      prevented LPS-delayed apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE LPS treatment
      delayed apoptosis of equine neutrophils in vitro for up to 24 hours in a dose
      dependent manner by alteration of the intrinsic pathway of apoptosis and was
      dependent on TLR4 signaling. Increased neutrophil life span may contribute to the
      development of a systemic inflammatory response syndrome in endotoxemic horses.

PMID- 29583050
TI  - Quantification of right ventricular volume measured by use of real-time three
      dimensional echocardiography and electrocardiography-gated 64-slice multidetector
      computed tomography in healthy dogs.
AB  - OBJECTIVE To evaluate accuracy of quantification of right ventricle volume (RVV)
      by use of 3-D echocardiography (3DE) and ECG-gated multidetector CT (MDCT).
      ANIMALS 6 healthy hound-cross dogs. PROCEDURES ECG-gated MDCT and complete 3DE
      examinations were performed on each dog. Right ventricular end-diastolic volumes
      (EDVs), end-systolic volumes (ESVs), stroke volume (SV), and ejection fraction
      (EF) were measured for 3DE and MDCT data sets by use of software specific for RVV
      quantification. Correlation and level of agreement between methods were
      determined. Intraobserver and interobserver variability were assessed for 3DE.
      RESULTS No significant differences were detected between SV and EF obtained with
      MDCT and 3DE. Significant differences were detected between right ventricular EDV
      and ESV obtained with MDCT and 3DE. No significant difference in heart rate was
      detected between methods. The correlation between MDCT and 3DE was very good (r =
      0.87) for EDV and ESV, moderate (r = 0.60) for EF, and poor (r = 0.31) for SV.
      Bland-Altman analysis revealed a systematic underestimation of RVV derived by use
      of 3DE, compared with the RVV derived by use of MDCT (mean bias, 15 and 10.3 mL
      for EDV and ESV, respectively). Intraobserver (EDV, 12%; ESV, 18%) and
      interobserver (EDV, 14%; ESV, 11%) variability were acceptable for 3DE.
      CONCLUSIONS AND CLINICAL RELEVANCE There was substantial variance for RVV
      measured by use of 3DE in healthy dogs and a significant underestimation of
      volumes, compared with results for MDCT, despite the fact there were no
      significant differences in SV and EF.

PMID- 29583052
TI  - Associations between dialysate sodium concentration and plasma sodium
      concentration of dogs receiving intermittent hemodialysis treatments.
AB  - OBJECTIVE To compare dialysate sodium concentration and patient plasma sodium
      concentration of dogs during intermittent hemodialysis treatments. SAMPLE 211
      intermittent hemodialysis treatments performed on 40 client-owned dogs for the
      management of dialysis-dependent uremia. PROCEDURES Medical records were reviewed
      to determine the plasma sodium concentration of each dog before and after routine
      hemodialysis treatments. Associations between detected changes in plasma sodium
      concentration and dialysate sodium concentration were evaluated by use of
      Spearman rank correlations and linear regression analysis. RESULTS Significant
      linear correlations were found between the dialysate sodium concentration and
      patient sodium concentration. The starting dialysate-to-patient sodium gradient
      was associated with the strongest correlation to the change in patient sodium
      concentration at the end of the dialysis session. Modest correlations existed
      between the dialysate sodium concentration and postdialysis patient sodium
      concentration as well as between the predialysis dialysate-to-patient sodium
      gradient and postdialysis dialysate-to-patient sodium gradient. CONCLUSIONS AND
      CLINICAL RELEVANCE The dialysate sodium concentration was correlated with the
      patient sodium concentration in dogs, and the dialysate-to-patient sodium
      gradient could be used to further refine this association to predict the
      postdialysis patient sodium concentration and potentially manage dysnatremia
      during hemodialysis. Prospective studies should be performed to determine how
      these associations can be used to correct aberrations as well as to avoid
      unwanted alterations in patient sodium concentrations.

PMID- 29583053
TI  - Correction: Pharmacokinetics of intravenous continuous rate infusions of sodium
      benzylpenicillin and ceftiofur sodium in adult horses.

PMID- 29583054
TI  - Sequencing of disease-modifying therapies for relapsing-remitting multiple
      sclerosis: a theoretical approach to optimizing treatment.
AB  - Multiple sclerosis (MS) is a chronic disease which usually begins in young
      adulthood and is a lifelong condition. Individuals with MS experience physical
      and cognitive disability resulting from inflammation and demyelination in the
      central nervous system. Over the past decade, several disease-modifying therapies
      (DMTs) have been approved for the management of relapsing-remitting MS (RRMS),
      which is the most prevalent phenotype. The chronic nature of the disease and the
      multiple treatment options make benefit-risk-based sequencing of therapy
      essential to ensure optimal care. The efficacy and short- and long-term risks of
      treatment differ for each DMT due to their different mechanism of action on the
      immune system. While transitioning between DMTs, in addition to immune system
      effects, factors such as age, disease duration and severity, disability status,
      monitoring requirements, preference for the route of administration, and family
      planning play an important role. Determining a treatment strategy is therefore
      challenging as it requires careful consideration of the differences in efficacy,
      safety and tolerability, while at the same time minimizing risks of immune
      modulation. In this review, we discuss a sequencing approach for treating RRMS,
      with importance given to the long-term risks and individual preference when
      devising a treatment plan. Evidence-based strategies to counter breakthrough
      disease are also addressed.

PMID- 29583055
TI  - Preparation of mesoporous silica microparticles by sol-gel/emulsion route for
      protein release.
AB  - Encapsulation of therapeutic proteins into particles from appropriate material
      can improve both stability and delivery of the drugs, and the obtained particles
      can serve as a platform for development of their new oral formulations. The main
      goal of this work was development of sol-gel/emulsion method for preparation of
      silica microcapsules capable of controlled release of encapsulated protein
      without loss of its native structure. For this purpose, the reported in
      literature direct sol-gel/W/O/W emulsion method of protein encapsulation was used
      with some modifications, because the original method did not allow to prepare
      silica microcapsules capable for protein release. The particles were synthesized
      using sodium silicate and tetraethoxysilane as silica precursors and different
      compositions of oil phase. In vitro kinetics of bovine serum albumin (BSA)
      release in buffer (pH 7.4) was studied by Fourier transform infrared (FTIR) and
      fluorescence spectrometry, respectively. Structural state of encapsulated BSA and
      after release was evaluated. It was found that the synthesis conditions
      influenced substantially the porous structure of the unloaded silica particles,
      release properties of the BSA-loaded silica particles and structural state of the
      encapsulated and released protein. The modified synthesis conditions made it
      possible to obtain the silica particles capable of controlled release of the
      protein during a week without loss of the protein native structure.

PMID- 29583056
TI  - Effect of an educational program based on cognitive behavioral techniques on fear
      of childbirth and the birth process.
AB  - OBJECTIVE: This study determined the effect of an educational program based on
      cognitive behavioral techniques (CBT) provided for pregnant women to address
      their fear of childbirth. METHODS: This study was conducted experimentally using
      pretest-posttest and a control group. A total of 111 Turkish pregnant women were
      recruited with 52 in the intervention group and 59 in the control group. The
      intervention group attended the educational program on coping with childbirth
      fears based on CBT, which took 3 weeks over six sessions. The Wijma Delivery
      Expectancy/Experience Questionnaire, version-A (W-DEQ-A) was administered to both
      groups as the posttest. The researchers monitored the pregnant women's labor and
      delivery and the State Anxiety Inventory (SAI), Numeric Pain Rating Scale (NPRS)
      and Birth Process Evaluation Form were completed. RESULTS: The post-education W
      DEQ-A score was 63.5 in the control group and 39.4 in the intervention group (p <
      .001). Their labor pain was lower, the second stage of labor was shorter and
      birth was more satisfactory for the intervention group than for the control group
      (p < .05). The CBT-based educational program and pain severity during childbirth
      were the significant predictors of satisfaction with childbirth (beta = 0.354;
      beta = -0.324, respectively; p < .05 for all). CONCLUSIONS: The CBT-based
      educational program on coping with childbirth fears reduced pregnant women's fear
      of childbirth and positively affected their birth experience.

PMID- 29583057
TI  - Remote Patient Monitoring and Clinical Outcomes for Postdischarge Patients with
      Type 2 Diabetes.
AB  - The objective of this study was to evaluate changes in clinical outcomes for
      patients with type 2 diabetes (T2D) after a 3-month remote patient monitoring
      (RPM) program, and examine the relationship between hemoglobin A1c (HbA1c)
      outcomes and participant characteristics. The study sample included 955 patients
      with T2D who were admitted to an urban Midwestern medical center for any reason
      from 2014 to 2017, and used RPM for 3 months after discharge. Clinical outcomes
      included HbA1c, weight, body mass index (BMI), and patient activation scores.
      Logistic regression was used to estimate the likelihood of having a
      postintervention HbA1c <9% by patient characteristics, among those who had
      baseline HbA1c >9%. Most patients experienced decreases in HbA1c (67%) and BMI
      (58%), and increases in patient activation scores (67%) (P < 0.001 in all 3
      cases) at the end of RPM. Logistic regression analyses revealed that among
      patients who had HbA1c >9% at baseline, men (odds ratio [OR] = 3.72; 95%
      confidence interval [CI], 1.43-9.64), those who had increased patient activation
      scores after intervention (OR = 1.05; 95% CI, 1.01-1.09), those who had higher
      baseline patient activation scores, and those who had a greater number of
      biometric data uploads during the intervention (OR = 1.02; 95% CI, 1.00-1.04)
      were more likely to have reduced their HbA1c to <9% at the end of RPM. RPM for
      postdischarge patients with T2D might be a promising approach for HbA1c control
      with increased patient engagement. Future studies with study designs that include
      a control group should provide more robust evidence.

PMID- 29583059
TI  - Conventional Drilling Versus Piezosurgery for Implant Site Preparation: A Meta
      Analysis.
AB  - The aim of this study was to evaluate if the stability of dental implants varies
      between dental implants placed by piezosurgery compared with those placed by
      conventional drilling. An electronic search in MEDLINE, SCOPUS, and the Cochrane
      Library was undertaken until August 2016 and was supplemented by manual searches
      and by unpublished studies at OpenGray. Only randomized controlled clinical
      trials that reported implant site preparation with piezosurgery and with
      conventional drilling were considered eligible for inclusion in this review. Meta
      analyses were performed to evaluate the impact of piezosurgery on implant
      stability. Of 456 references electronically retrieved, 3 were included in the
      qualitative analysis and quantitative synthesis. The pooled estimates suggest
      that there is no significant difference between piezosurgery and conventional
      drilling at baseline (weighted mean differences [WMD]: 2.20; 95% confidence
      interval [CI]: -5.09, 9.49; P = .55). At 90 days, the pooled estimates revealed a
      statistically significant difference (WMD: 3.63; 95% CI: 0.58, 6.67, P = .02)
      favoring piezosurgery. Implant stability may be slightly improved when osteotomy
      is performed by a piezoelectric device. More randomized controlled clinical
      trials are needed to confirm these findings.

PMID- 29583058
TI  - Early Postpartum Hemoglobin Less Than 10 g/dL Is Associated with Future Maternal
      Atherosclerotic Morbidity.
AB  - OBJECTIVE: Anemia is associated with increased cardiovascular morbidity in the
      general population. Anemia is common during pregnancy. We examined the
      association between anemia at the very early postpartum period and long-term
      atherosclerotic-related morbidity. PATIENTS AND METHODS: A retrospective study
      including women who gave birth between 1988 and 2013 was conducted. The women
      were divided into two groups according to hemoglobin (Hb) value on the first day
      after delivery: Hb <10 g/dL and Hb >=10 g/dL. We examined the rates of
      hospitalization due to atherosclerotic-related morbidity, which were classified
      into minor and major events. The follow-up period was from the index birth until
      either hospitalization or the end of study period. Survival estimates were
      calculated by Kaplan-Meier survival analysis. Cox proportional hazards models
      were used to evaluate whether Hb <10 gr/dL is an independent risk factor for long
      term atherosclerotic events. RESULTS: The study population included 30,088
      (37.40%) women with Hb <10 g/dL and 50,354 (63%) women with Hb >=10 g/dL at the
      index birth. The hospitalization incidence density was higher in the Hb <10 g/dL
      group versus the Hb >=10 g/dL group, for total atherosclerotic- related
      hospitalizations (4.35 vs. 3.76, p < 0.001), and hospitalization for major events
      (1.83 vs. 1.51, p < 0.001) and minor events (2.60 vs. 2.31, p < 0.001). In Cox
      proportional hazards models, it was demonstrated that Hb <10 g/dL was
      independently associated with total hospitalizations (HR 1.13; CI: 1.04-1.24 p =
      0.004) and hospitalizations for major events (HR 1.16; CI: 1.01-1.34 p = 0.034)
      Conclusions: Hb <10 g/dL at the very early postpartum period might be a marker
      for long-term atherosclerotic-related morbidity.

PMID- 29583061
TI  - Correction to: Green et al., Test-enhanced learning in health professions
      education: A systematic review: BEME Guide No. 48.

PMID- 29583060
TI  - PAPep Inhibits Secretion of Poly(I:C)-Induced Inflammatory Cytokines and ICAM-1
      Expression in Corneal Fibroblasts by Suppressing the NF-kappaB/p38 Pathway.
AB  - PURPOSE: To assess the anti-inflammatory effect and mechanism of a novel peptide,
      PAPep, in poly(I:C)-stimulated corneal fibroblasts. METHODS: Corneal fibroblasts
      were treated with poly(I:C) to elicit inflammation. Real-time polymerase chain
      reaction (PCR) and ELISA were used to measure the mRNA and protein levels of
      interleukin (IL)-6, monocyte chemotactic factor (MCP)-1, and interferon gamma
      (IFN-gamma). Real-time PCR, immunofluorescence, and immunoblot were performed to
      determine ICAM-1 expression. Translocation of NF-kappaB p65 was observed by
      immunofluorescence. Phosphorylation of IkappaBalpha, NF-kappaB, and mitogen
      activated protein kinase (MAPK) (p38, JNK and ERK) were detected by western blot.
      RESULTS: The results showed that PAPep effectively decreased mRNA and protein
      expression of IL-6, MCP-1, and IFN-gamma in corneal fibroblasts exposed to
      poly(I:C). In addition, PAPep reduced mRNA and protein levels of ICAM-1. The NF
      kappaB and MAPK(p38) pathway were inhibited by PAPep treatment, as indicated by
      suppression of p65 nuclear translocation, and IkappaBalpha, NF-kappaB, and p38
      activation. PAPep showed no effect on JNK or ERK activity. CONCLUSIONS: PAPep
      attenuates the expression of inflammatory cytokines and ICAM-1 in corneal
      fibroblasts induced by poly(I:C) through blocking the NF-kappaB and MAPK(p38)
      pathway. PAPep may be considered a promising therapeutic agent for treating viral
      keratitis.

PMID- 29583062
TI  - Process Evaluation for Improving K12 Program Effectiveness: Case Study of a
      National Institutes of Health Building Interdisciplinary Research Careers in
      Women's Health Research Career Development Program.
AB  - INTRODUCTION: Process evaluation is an important tool in quality improvement
      efforts. This article illustrates how a systematic and continuous evaluation
      process can be used to improve the quality of faculty career development programs
      by using the University of Minnesota's Building Interdisciplinary Research
      Careers in Women's Health (BIRCWH) K12 program as an exemplar. METHODS: Data from
      a rigorous process evaluation incorporating quantitative and qualitative
      measurements were analyzed and reviewed by the BIRCWH program leadership on a
      regular basis. RESULTS: Examples are provided of how this evaluation model and
      processes were used to improve many aspects of the program, thereby improving
      scholar, mentor, and advisory committee members' satisfaction and scholar
      outcomes. CONCLUSIONS: A rigorous evaluation plan can increase the effectiveness
      and impact of a research career development plan.

PMID- 29583063
TI  - Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine
      Stains Compared with Single Pass: A Randomized Comparison with Histological
      Examination.
AB  - OBJECTIVE: To compare the efficacy and safety of double-pass pulsed dye laser
      (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS).
      BACKGROUND: The increase in the extent of vascular damage attributed to the use
      of double-pass techniques for PWS remains inconclusive. A prospective, side-by
      side comparison with a histological study for virgin PWS is still lacking.
      MATERIALS AND METHODS: Twenty-one patients (11 flat PWS, 10 hypertrophic PWS)
      with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was
      divided into three treatment sites: SWL, DWL, and untreated control. Chromametric
      and visual evaluation of the efficacy and evaluation of side effects were
      conducted 3 months after final treatment. Biopsies were taken at the treated
      sites immediately posttreatment. RESULTS: Chromametric and visual evaluation
      suggested that DWL sites showed no significant improvement compared with SWL (p >
      0.05) in treating PWS. The mean depth of photothermal damage to the vessels was
      limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side
      effects were not observed in any patients. CONCLUSIONS: Double-pass PDL does not
      enhance PWS clearance. To improve the clearance of PWS lesions, either the depth
      of laser penetration should be increased or greater photothermal damage to
      vessels should be generated.

PMID- 29583064
TI  - Prescribing Bioidentical Menopausal Hormone Therapy: A Survey of Physician Views
      and Practices.
AB  - BACKGROUND: It is estimated that 1-2.5 million U.S. women use compounded
      bioidentical menopausal hormone therapy (MHT). However, the proportion of
      American physicians prescribing compounded bioidentical hormones remains unknown.
      This study aims to evaluate obstetrician-gynecologists' (OB/GYNs) and family
      medicine physicians' decisions reflected in prescribing practices of MHT in
      Kansas, and level of agreement with the American College of Obstetricians and
      Gynecologists (ACOG) recommendations. METHODS: An Internet-based 38-item survey
      was electronically disseminated to OB/GYNs and family medicine physicians
      identified through the Kansas State Board of Healing Arts licensure list.
      RESULTS: Out of 1349 physicians contacted, 164 (12.2%) responded to the survey.
      There were 128 (9.5%) responses included in the final analysis. In the past year,
      96.1% (123/128) of respondents prescribed conventional MHT, 93.0% (119/128)
      prescribed Food and Drug Administration (FDA)-approved bioidentical MHT, and
      66.1% (84/127) prescribed compounded bioidentical MHT. Of factors influencing MHT
      prescribing practices, FDA regulation was not important to 16.7% (21/126) of
      physicians, whereas customization was important to 68.5% (87/127). There was a
      significant difference between specialties, 37.7% of OB/GYNs compared with 56.9%
      of family medicine physicians, regarding the ACOG statement that "patients should
      be counseled that conventional MHT is more appropriate than compounded
      preparations" (p = 0.031). Respondents disagreed with ACOG regarding the
      statements that "the practice of compounding makes it difficult to identify the
      active agent responsible for various effects" (41.0% of OB/GYNs and 34.8% of
      family medicine physicians) and "the practice of custom blending commercially
      available drug products lacks both a strong biological rationale and medical
      evidence for effectiveness" (36.1% of OB/GYNs and 37.9% of family medicine
      physicians). CONCLUSIONS: Prescribing practices for MHT vary between specialties.
      This study identifies a meaningful level of disagreement with ACOG
      recommendations regarding prescription of compounded rather than FDA-approved
      MHT. Further research is needed to better understand this level of discordance.

PMID- 29583065
TI  - Lack of Impact of the 2009 USPSTF Guidelines on Rates of Mammography Screening.
AB  - BACKGROUND: In November 2009, the United States Preventive Services Task Force
      (USPSTF) changed their mammography screening guidelines from recommending a
      screen every 1-2 years for women older than 40 years. The revised guideline
      recommends against regular screening for women aged 40-49 and recommends biennial
      screening for women aged 50-74. RESEARCH DESIGN: We used autoregressive
      integrated moving-average (ARIMA) time series modeling to estimate the effect of
      the USPSTF 2009 guidelines on trends in screening rates. Enrollment and encounter
      files from the PharMetrics LifeLink+ commercial insurance claims database, years
      2006-2014, were linked to determine monthly screening rates. The main outcome
      measure was mammography screening rates per 1,000 commercially insured women aged
      40-49 or aged 50-64. RESULTS: The study sample included 493,347 women aged 40-49
      years with at least 1 month of eligibility and 658,052 women aged 50-64 years
      with at least 1 month of eligibility. There were 1,305,375 total screening
      mammograms from 2007 to 2014. Average monthly mammography screening rates from
      2007 to 2014 were 40.4 per 1,000 women aged 40-49 and 54.8 per 1,000 women aged
      50-64. There was a temporary decline in monthly screening rates of 11.8% and
      11.2% for the 40-49 and 50-64 age groups, respectively, in the 2-month period
      after the guideline change (January and February 2010), but the rates quickly
      returned to pre-USPSTF trend levels afterward. CONCLUSION: Implementation of the
      USPSTF 2009 guidelines was not associated with a persistent long-term change in
      mammography screening rates over the next 5 years, despite a temporary decline of
      2 months immediately following the guidelines.

PMID- 29583066
TI  - Naturally Occurring Hair Growth Peptide: Water-Soluble Chicken Egg Yolk Peptides
      Stimulate Hair Growth Through Induction of Vascular Endothelial Growth Factor
      Production.
AB  - Alopecia is divided into two categories: androgenic alopecia and nonandrogenic
      alopecia. An androgen-dependent abnormality of biological functions causes
      alopecia in males, but the role of androgens is not yet elucidated in female
      pattern hair loss (FPHL). Modulation of androgenic activity is not effective in
      certain kinds of androgenic alopecia in females, as well as in cases of
      nonandrogenic alopecia in males and females. The hair growth drug, minoxidil,
      stimulates vascular endothelial growth factor (VEGF) production as well as
      vascularization and hair growth in females. Yet, because minoxidil has side
      effects with long-term use, a safe alternative hair growth agent is needed.
      Whereas hair develops after birth in mammalian species, hair mostly grows in a
      precocial bird, in the chicken, between hatching days 14 and 15. Therefore, we
      hypothesized that the chicken egg contains a key hair growth factor. In this
      study, we demonstrated that water-soluble peptides derived from the egg yolk
      stimulate VEGF production and human hair follicle dermal papilla cell growth. We
      also found that these peptides enhance murine hair growth and improve hair growth
      in FPHL. Finally, we characterized that water-soluble egg yolk peptides induce
      VEGF expression through insulin growth factor-1 receptor activation-induced
      hypoxia-inducible factor-1alpha transcription pathway. We have given the name
      "hair growth peptide (HGP)" to this water-soluble egg yolk peptide.

PMID- 29583067
TI  - Neurofibromatous neuropathy: An ultrastructural study.
AB  - Plexiform neurofibroma is pathognomonic of neurofibromatosis 1 (NF1). An NF1
      associated peripheral neuropathy has been described in a small minority of NF1
      patients but its histopathological features are poorly characterized. We report
      the case of a 46-year-old woman presenting with bilateral supraclavicular painful
      masses without other stigmata of NF1. MRI showed bilateral plexiform lesions
      extending from cervical roots to the elbows. Nerve conduction studies documented
      a sensory motor polyneuropathy. Morphometric analysis of sural nerve biopsy
      showed a preferential loss of large-caliber myelinated fibers with a g ratio of
      0.515, and the presence of regeneration clusters. By electron microscopy, marked
      and diffuse endoneurial fibrosis with an altered relationship between Schwann
      cells (SC) and collagen fibrils was observed. Moreover both myelinating and non
      myelinating SC were characterized by the presence of various cell degradation
      products. These changes suggest that, in neurofibromatous neuropathy, a
      widespread axonal atrophy and degeneration take place independently on the
      presence of tumoral infiltration, possibly due to an impairment in SC-axon cross
      talk. In this case, the coexistence of plexiform neurofibromas with a peripheral
      neuropathy strongly suggests a diagnosis of NF1 even without fulfillment of
      clinical criteria. We propose that in the presence of plexiform neurofibromas,
      electrophysiological studies should be performed also in asymptomatic patients,
      in order to detect the existence of a subclinical neuropathy.

PMID- 29583069
TI  - Associations Among Sleep, Body Mass Index, Waist Circumference, and Risk of Type
      2 Diabetes Among U.S. Childbearing-Age Women: National Health and Nutrition
      Examination Survey.
AB  - BACKGROUND: Women of childbearing age (18-44 years) present an important group
      for understanding sleep, but few studies have focused on this population. No
      study has investigated the associations among sleep, overweight/obesity, and risk
      of type 2 diabetes among childbearing-age women in the National Health and
      Nutrition Examination Survey (NHANES). METHODS: Data were from NHANES, 2005-2008.
      The study population consisted of 18-44 year old women. Pregnant women and those
      diagnosed with sleep disorders were excluded. Sleep duration and quality were
      self-reported. Body mass index (BMI), waist circumference (WC) measurements, and
      a 2-hour 75 g oral glucose tolerance test (OGTT) were performed by trained NHANES
      staff. An unadjusted linear regression analysis; a second adjusted for
      demographics only (partially adjusted model); and a third adjusted for
      demographics and variables associated with overweight/obesity and diabetes (fully
      adjusted model) were computed to assess associations among sleep duration/quality
      and BMI, WC, and 2-hour OGTT. RESULTS: Total sample consisted of 2388
      childbearing-age women. Only sleep duration was significantly associated with BMI
      and WC in the unadjusted and partially adjusted models, but was no longer
      significant in the fully adjusted model. Neither sleep duration nor quality was
      significantly associated with 2-hour OGTT in any of the models. CONCLUSIONS:
      Targeting sleep duration and sleep quality alone would not likely contribute to
      significantly lower BMI, WC, or risk of type 2 diabetes in US childbearing-age
      women. Additional studies, especially longitudinal ones using objective measures
      of sleep, are needed to confirm these findings.

PMID- 29583068
TI  - HLPI-Ensemble: Prediction of human lncRNA-protein interactions based on ensemble
      strategy.
AB  - LncRNA plays an important role in many biological and disease progression by
      binding to related proteins. However, the experimental methods for studying
      lncRNA-protein interactions are time-consuming and expensive. Although there are
      a few models designed to predict the interactions of ncRNA-protein, they all have
      some common drawbacks that limit their predictive performance. In this study, we
      present a model called HLPI-Ensemble designed specifically for human lncRNA
      protein interactions. HLPI-Ensemble adopts the ensemble strategy based on three
      mainstream machine learning algorithms of Support Vector Machines (SVM), Random
      Forests (RF) and Extreme Gradient Boosting (XGB) to generate HLPI-SVM Ensemble,
      HLPI-RF Ensemble and HLPI-XGB Ensemble, respectively. The results of 10-fold
      cross-validation show that HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB
      Ensemble achieved AUCs of 0.95, 0.96 and 0.96, respectively, in the test dataset.
      Furthermore, we compared the performance of the HLPI-Ensemble models with the
      previous models through external validation dataset. The results show that the
      false positives (FPs) of HLPI-Ensemble models are much lower than that of the
      previous models, and other evaluation indicators of HLPI-Ensemble models are also
      higher than those of the previous models. It is further showed that HLPI-Ensemble
      models are superior in predicting human lncRNA-protein interaction compared with
      previous models. The HLPI-Ensemble is publicly available at:
      http://ccsipb.lnu.edu.cn/hlpiensemble/ .

PMID- 29583070
TI  - A developmental cascade perspective of paediatric obesity: a conceptual model and
      scoping review.
AB  - Considering the immense challenge of preventing obesity, the time has come to
      reconceptualise the way we study the obesity development in childhood. The
      developmental cascade model offers a longitudinal framework to elucidate the way
      cumulative consequences and spreading effects of risk and protective factors,
      across and within biopsychosocial spheres and phases of development, can propel
      individuals towards obesity. In this article, we use a theory-driven model
      building approach and a scoping review that included 310 published studies to
      propose a developmental cascade model of paediatric obesity. The proposed model
      provides a basis for testing hypothesised cascades with multiple intervening
      variables and complex longitudinal processes. Moreover, the model informs future
      research by resolving seemingly contradictory findings on pathways to obesity
      previously thought to be distinct (low self-esteem, consuming sugary foods, and
      poor sleep cause obesity) that are actually processes working together over time
      (low self-esteem causes consumption of sugary foods which disrupts sleep quality
      and contributes to obesity). The findings of such inquiries can aid in
      identifying the timing and specific targets of preventive interventions across
      and within developmental phases. The implications of such a cascade model of
      paediatric obesity for health psychology and developmental and prevention
      sciences are discussed.

PMID- 29583071
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PMID- 29583072
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PMID- 29583073
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PMID- 29583074
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PMID- 29583075
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PMID- 29583076
TI  - How Do Adolescents Affected by Cancer Experience a Hospital Environment?
AB  - PURPOSE: Adolescence is a transition period involving complex development
      processes. A life-threatening disease like cancer jeopardizes this development
      and often exposes adolescents to hospital environments that are unadjusted to
      them. Despite growing research on how the physical environment affects the well
      being of the (child as) patient, adolescents are often overlooked. We
      investigated how adolescents experience a hospital stay and how the physical
      environment influences that experience. METHODS: We interviewed ten adolescents
      who are or have been affected by cancer between the age of 14 and 25, and
      discussed preliminary findings with professional experts. RESULTS: In young
      people's experience of a hospital environment three interrelated themes stand
      out: support, distraction, control, and autonomy. Adolescent patients primarily
      look for connections with life outside the hospital. The hospital confronts them
      with different obstacles, most of which appear to relate to difficulties
      concerning the loss of these connections. These obstacles include a lack of
      freedom, control, and autonomy; limited social interaction with friends;
      inability to participate in daily activities; boredom; and a lack of privacy.
      CONCLUSION: As a group, adolescent patients clearly have specific characteristics
      and needs. This specificity, which is largely hidden in the development and
      transition they are undergoing, explains the need for a hospital environment
      dedicated to them-be it a separate adolescent ward, or the grouping of
      adolescents on children's and/or adult wards. Rather than focusing on a
      superficial list of wishes and needs, the design of this environment should
      consider the specific reasons driving adolescents' wishes and needs.

PMID- 29583077
TI  - Putting Referrals from Family Planning Providers in Context.

PMID- 29583078
TI  - Effectiveness and Safety of Treatment with Direct Oral Anticoagulant Rivaroxaban
      in Patients with Slow-Flow Vascular Malformations: A Case Series.
AB  - BACKGROUND: Slow-flow vascular malformations (VM) can be associated with
      localized intravascular coagulopathy (LIC) that is characterized by elevated D
      Dimer levels and low fibrinogen and platelets. This can lead to bleeding and
      clotting tendencies, which can give rise to functional limitations such as pain
      and swelling and even progress to disseminated intravascular coagulopathy.
      METHODS AND RESULTS: We conducted a chart review of four patients with evidence
      of LIC who were started on rivaroxaban. We found an improvement of D-Dimer and/or
      fibrinogen levels in all four patients. They also had an improvement of pain and
      functionality. CONCLUSIONS: We report on four patients in whom anticoagulation
      with a direct oral anticoagulant, rivaroxaban, was effective in controlling signs
      and symptoms of consumptive coagulopathy with no evidence of bleeding from the
      use of rivaroxaban.

PMID- 29583079
TI  - Stigma-related access barriers and violence against trans women in the Colombian
      healthcare system.
AB  - Drawing from qualitative research conducted in a participatory action research
      framework with 28 transgender women in Colombia, this paper presents the stigma
      related barriers to healthcare experienced by trans women and their experiences
      of multi-level violence within the healthcare system. The authors also discuss
      how advocacy work was conducted as part of the research process and how trans
      community leaders were involved throughout the project in order to promote policy
      relevance and community-based implementation of findings. The paper concludes
      with a discussion of how the experiences of violence and stigmatisation within
      the health care system is linked to broader processes of structural stigma
      reproduced within Colombian society.

PMID- 29583080
TI  - Optimal Laser Phototherapy Parameters for Pain Relief.
AB  - BACKGROUND AND OBJECTIVE: Studies on laser phototherapy for pain relief have used
      parameters that vary widely and have reported varying outcomes. The purpose of
      this study was to determine the optimal parameter ranges of laser phototherapy
      for pain relief by analyzing data aggregated from existing primary literature.
      MATERIALS AND METHODS: Original studies were gathered from available sources and
      were screened to meet the pre-established inclusion criteria. The included
      articles were then subjected to meta-analysis using Cohen's d statistic for
      determining treatment effect size. From these studies, ranges of the reported
      parameters that always resulted into large effect sizes were determined. These
      optimal ranges were evaluated for their accuracy using leave-one-article-out
      cross-validation procedure. RESULTS: A total of 96 articles met the inclusion
      criteria for meta-analysis and yielded 232 effect sizes. The average effect size
      was highly significant: d = +1.36 [confidence interval (95% CI) = 1.04-1.68].
      Among all the parameters, total energy was found to have the greatest effect on
      pain relief and had the most prominent optimal ranges of 120-162 and 15.36-20.16
      J, which always resulted in large effect sizes. The cross-validation accuracy of
      the optimal ranges for total energy was 68.57% (95% CI = 53.19-83.97). Fewer and
      less-prominent optimal ranges were obtained for the energy density and duration
      parameters. None of the remaining parameters was found to be independently
      related to pain relief outcomes. CONCLUSIONS: The findings of meta-analysis
      indicate that laser phototherapy is highly effective for pain relief. Based on
      the analysis of parameters, total energy can be optimized to yield the largest
      effect on pain relief.

PMID- 29583082
TI  - Test Selection for Women with Suspected Stable Ischemic Heart Disease.
AB  - Ischemic heart disease (IHD) is the leading cause of death and disability among
      women in the United States. Identifying IHD in women presenting with stable
      symptoms and stratifying their risk for an IHD event can be challenging for
      providers, with several different tests available. This article is meant to serve
      as a practical guide for clinicians treating women with potentially ischemic
      symptoms. Evidence and American Heart Association (AHA) recommendations regarding
      test selection are reviewed, with a focus on the information to be gained from
      each test. We outline suggested courses of action to be taken in the case of a
      positive or negative test. Regardless of the initial test result, clinicians
      should view a woman's symptom presentation as an opportunity to review and modify
      her risk of cardiovascular events.

PMID- 29583081
TI  - Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent
      High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis.
AB  - BACKGROUND: High triglycerides (TG) and diabetes mellitus type 2 (DM2) are
      stronger predictors of cardiovascular disease (CVD) in women than in men, but few
      randomized, controlled clinical trials have investigated lipid-lowering
      interventions in women and none have reported results specifically in women with
      high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic
      acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG
      >=500 mg/dL. METHODS: The 12-week ANCHOR trial randomized 702 statin-treated
      patients (73% with DM; 39% women) at increased CVD risk with TG 200-499 mg/dL
      despite controlled low-density lipoprotein cholesterol (LDL-C; 40-99 mg/dL) to
      receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis
      included 146 women with DM2 (97% white, mean age 62 years) randomized to
      icosapent ethyl 4 g/day (n = 74) or placebo (n = 72). RESULTS: Icosapent ethyl
      significantly reduced TG (-21.5%; p < 0.0001) without increasing LDL-C and
      lowered other potentially atherogenic lipid/lipoprotein, apolipoprotein, and
      inflammatory parameters versus placebo. Icosapent ethyl increased EPA levels in
      plasma (+639%; p < 0.0001; n = 49) and red blood cells (+599%; p < 0.0001; n =
      47) versus placebo. Safety and tolerability of icosapent ethyl were generally
      similar to placebo. CONCLUSION: In women with DM2 at high CVD risk with
      persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially
      atherogenic parameters with safety and tolerability comparable to placebo.
      Potential CVD benefits of icosapent ethyl are being tested in ~8000 men and women
      at high CVD risk with high TG on statins in the ongoing Reduction of
      Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT)
      cardiovascular (CV) outcome trial.

PMID- 29583083
TI  - Postmenopausal Osteoporosis: A Clinical Review.
AB  - In postmenopausal women, osteoporotic fractures are more common than stroke,
      myocardial infarction, and breast cancer combined, and fractures can be costly
      and result in disability or death. Because there are no signs or symptoms of
      osteoporosis other than fracture, risk assessment is necessary to identify those
      at higher risk for clinical events. For women, a clinical fracture risk
      assessment (FRAX) is appropriate at menopause. Bone mineral density (BMD)
      measurement is recommended for women at age 65, and earlier for those who have
      risk factors. Adequate calcium, vitamin D, and weight-bearing exercise are
      important for bone health at all ages, and those at high risk for fracture based
      on BMD or FRAX should be offered medical therapy to reduce fracture risk after an
      appropriate medical evaluation. Bisphosphonates can accumulate in bone, so after
      a period of treatment, lower risk patients may be offered a period off drug
      therapy. However, the effects of denosumab are not sustained when treatment is
      discontinued, so there is no "drug holiday" with denosumab. Anabolic therapy can
      be offered to those with higher risk for fracture. Although rare safety concerns
      regarding atypical femoral fracture and osteonecrosis of the jaw have received
      prominent attention, for patients who are appropriately treated according to
      National Osteoporosis Foundation guidelines, the benefit of hip fracture risk
      reduction far outweighs the risk of these uncommon side effects. Accurate
      information for patients and shared decision-making are important for acceptance
      and persistent with appropriate treatment.

PMID- 29583084
TI  - The Effect of Cervical Smears Performed by General Practitioners on the Cervical
      Cancer Screening Rate of their Female Patients: A Claim Database Analysis and
      Cross-Sectional Survey.
AB  - PURPOSE: Cervical cancer screening reduces the incidence and specific mortality
      rate of cervical neoplasms. In most cases screening by means of Pap smears is
      performed in France by gynecologists. The primary objective of this study was to
      confirm whether the participation rate is increased when general practitioners
      (GPs) carry out the smears themselves. The secondary objective was to evaluate
      other independent characteristics of GPs predicting participation rates in women.
      METHODS: The population of 347 GPs, including their relevant characteristics and
      their 90,094 female patients eligible for screening over 2 years (2013-2014), was
      derived from the SIAM claim database of the Flanders Healthcare Insurance Fund
      (CPAM). A telephone survey among all GPs was carried out to know whether they
      were performing smears in their surgeries. RESULTS: A total of 343 GPs were
      included for analysis (98.8% participation rate). The mean cervical cancer
      screening participation rate over 2 years among all the women in the recommended
      age group (25-65 years) was 43.3% (+/-6.9). Bivariate analysis showed that
      participation rate was higher when the GP performed smears (adjusted difference
      of mean: 2.06 [95% CI: 0.67-3.45], p = 0.037) and whether the GP was female (2.08
      [0.42-3.74], p = 0.0144). After multivariate analysis the only significant
      characteristic of the GP was the performance of smears (1.71 [0.27-3.16], p =
      0.0204). CONCLUSIONS: Cervical smears performed by GPs led to increased screening
      participation rates within the recommended age group of women. However, the size
      of this increase is insufficient to reach the expected participation rates.

PMID- 29583086
TI  - Dual infection of the central nervous system caused by Cryptococcus and
      Toxoplasma in a patient with AIDS: a case report and literature review.
AB  - Dual infection of the central nervous system secondary to Cryptococcus and
      Toxoplasma is very uncommon, even in the setting of acquired immunodeficiency
      syndrome (AIDS). We report the case of a 52-year-old patient who was admitted
      with multiple cranial nerve deficits. Magnetic resonance imaging showed
      supratentorial and infratentorial enhancing lesions. He was newly diagnosed with
      HIV infection with a CD4 count of 59 cells/uL and HIV viral load of 299,619
      copies/mL. Diagnosis of Cryptococcus meningitis was made by Cryptococcal antigen
      in cerebrospinal fluid (CSF). The high clinical suspicion for Toxoplasmosis
      prompted an early empiric treatment for this condition. The diagnosis of
      Toxoplasmosis was later confirmed by PCR in CSF. Despite an adequate treatment
      for these two pathologies, his condition deteriorated and eventually expired. We
      reviewed the English language literature for cases of Cryptococcus and Toxoplasma
      co-infection of the central nervous system in patients with AIDS. To our
      knowledge, our patient is the third case of simultaneous infection described in
      the literature. Clinicians must be aware that focal brain lesions in patients
      with cryptococcal meningitis should prompt a full evaluation to search for
      concomitant pathologies of which Toxoplasmosis is the most important. Our case
      illustrates the utility of PCR in CSF for an early diagnosis of toxoplasmosis,
      reserving brain biopsy for cases of anti-toxoplasma therapy failure.

PMID- 29583087
TI  - Regulation of Constitutive Tip110 Expression in Human Cord Blood CD34+ Cells
      Through Selective Usage of the Proximal and Distal Polyadenylation Sites Within
      the 3'Untranslated Region.
AB  - Tip110 plays important roles for stem cell pluripotency and hematopoiesis.
      However, little is known about the regulatory mechanisms of Tip110 expression in
      this process. In this study, we first showed that constitutive Tip110 expression
      was cell proliferation and differentiation dependent and self-regulated in both
      human cord blood CD34+ cells. Using a series of molecular techniques, we found
      that ectopic Tip110 expression led to increased constitutive Tip110 expression
      through its 3'-untranslated region (3'UTR), specifically through preferential
      usage of proximal polyadenylation sites within its 3'UTR in cells, including
      human cord blood CD34+ cells, which indeed led to an increased number of CD34+
      cells during differentiation of those cells. Lastly, we showed that Tip110
      protein interacted with cleavage stimulation factor 64 (CstF64) protein and that
      more CstF64 was recruited to the promixal polyadenylation site than the distal
      polyadenylation site within its 3'UTR. These finding together demonstrates that
      constitutive Tip110 expression is regulated, at least in part, through its
      interaction with CstF64, recruitment of CstF64 to, and selective usage of those
      two polyadenylation sites within its 3'UTR.

PMID- 29583085
TI  - Functional Heterogeneity of Endothelial Cells Derived from Human Pluripotent Stem
      Cells.
AB  - Specification of endothelial cells (ECs) into arterial, venous, and lymphatic
      cells is a crucial process of vascular development, and expanding our knowledge
      about EC specification from human pluripotent stem cells (hPSCs) will aid the
      design of optimal strategies for producing desired types of ECs for therapies. In
      our prior studies, we revealed that hPSC-derived VE-cadherin(V)+CD31+CD34+ ECs
      are heterogeneous and include at least three major subsets with distinct
      hemogenic properties: V+CD43/235a-CD73- hemogenic endothelial progenitors (HEPs),
      V+CD43loCD235a+73- angiogenic hematopoietic progenitors (AHPs), and V+CD43/235a
      73+ non-HEPs. In this study, using angiogenesis assays, we demonstrated that ECs
      within these subsets have distinct endothelial colony- and tube-forming
      properties, proliferative and migratory properties, and endothelial nitric oxide
      synthase and inflammatory cytokine production potentials. Culture of isolated
      subsets in arterial, venous, and lymphatic conditions revealed that AHPs are
      skewed toward lymphatic, HEPs toward arterial, and non-HEPs toward venous
      differentiation in vitro. These findings suggest that selection and enhancement
      of production of a particular EC subset may aid in generating desirable EC
      populations with arterial, venous, or lymphatic properties from hPSCs.

PMID- 29583088
TI  - Development and performance assessment of electrically heated gloves with smart
      temperature control function.
AB  - A pair of lightweight electrically heated gloves (EHG) with smart temperature
      control function was developed. To evaluate the thermoregulation properties of
      the EHG, human trials were conducted in a climate chamber (2.5  degrees C, 60%
      RH). The changes in skin temperature at all fingers and the opisthenar, and the
      subjective thermal sensation were recorded over 60 min. The effects of two air
      velocities (i.e., 0.17 and 0.50 m/s) on the cold protective performance of the
      EHG in scenarios of heating and control were also investigated. For heating
      scenarios, skin temperature and thermal sensation at all fingers and the
      opisthenar were found significantly higher than those in control conditions.
      Moreover, the air velocity at 0.50 m/s greatly reduced the cold protective
      performance of the gloves. The research findings can be applied to improve
      thermal comfort and extend working times for persons in cold environments.

PMID- 29583089
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PMID- 29583090
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PMID- 29583091
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PMID- 29583092
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PMID- 29583093
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PMID- 29583094
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PMID- 29583095
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PMID- 29583096
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PMID- 29583097
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PMID- 29583098
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PMID- 29583099
TI  - Time course of the response to navigated repetitive transcranial magnetic
      stimulation at 10 Hz in chronic neuropathic pain.
AB  - Objective This prospective study evaluated the time to response and outcomes of
      navigated repetitive transcranial magnetic stimulation (TMS) at a frequency of 10
      Hz in patients with chronic neuropathic pain. Methods This prospective study
      included patients with unilateral chronic neuropathic pain. All patients received
      motor cortex stimulation at 10 Hz over nine consecutive days using repetitive
      TMS. Outcome was evaluated over a six-week follow-up period using the visual
      analogue scale, the German Pain Questionnaire and time to pain reduction. Results
      Fifty patients (23 female, 27 male) were recruited. Two patients were excluded
      from analysis owing to premature discontinuation of treatment and follow-up.
      31/48 patients in the cohort suffered from atypical facial pain. The pain
      duration ranged approximately from six months to 27 years. After six weeks, 28/46
      patients reported a significant level of pain relief (P < 0.001). Conclusion
      Navigated repetitive TMS for chronic pain is a non-invasive modality with
      demonstrable clinical benefit. In particular, patients with atypical facial pain
      with a clear clinicoanatomical correlate responded well to high-frequency
      stimulation. Patients with a mean pain history of less than five years benefited
      significantly from this treatment, so early treatment with repetitive TMS should
      be encouraged.

PMID- 29583100
TI  - ?

PMID- 29583101
TI  - Safety of percutaneous axillary artery access with a suture-mediated closing
      device for parallel endograft aortic procedures - a retrospective pilot study.
AB  - BACKGROUND: The aim of this study was to evaluate the technical success of
      percutaneous ultrasound-guided access to the infraclavicular axillary artery with
      a suture-mediated closing device for patients requiring large-sized upper
      extremity access. PATIENTS AND METHODS: In 18 consecutive patients (17 male, one
      female, mean age 73.5 +/- 9.6 years, range 52-88 years), artery accesses with the
      preclosing modification for chimney endografts was gained with 20 ultrasound
      guided infraclavicular axillary. Retrospectively, the following endpoints were
      analysed: technical success of percutaneous ultrasound-guided puncture of the
      infraclavicular axillary artery as well as introduction and deployment, primary
      successful haemostasis by preclosing, bailout procedures, overall complication
      rate including local vascular, cerebrovascular, and peripheral neurological
      complications. RESULTS: Ultrasound-guided puncture and preclosing procedure was
      successful in all patients. Mean sheath size was 9.4 +/- 1.6 French. Ultrasound
      guided puncture as well as introduction and deployment were successful in all
      patients (100 %). Primary successful haemostasis by preclosing was 70 % (14/20).
      Postclosing with one or two devices enabled successful haemostasis in another 15
      %. Bailout stent graft implantation was necessary in three accesses (15 %),
      either by transfemoral (n = 2) or transbrachial (n = 1) route. Overall
      complication rate was 16.5 %, all of them were minor haematomas. CONCLUSIONS:
      Percutaneous ultrasound-guided infraclavicular axillary artery access with
      preclosing modification seems feasible and safe. The access related complication
      rate is low and complications can potentially be managed by endovascular means.

PMID- 29583103
TI  - The rural interdisciplinary team training program: a workforce development
      workshop to increase geriatrics knowledge and skills for rural providers.
AB  - The Rural Interdisciplinary Team Training Program (RITT) is a team-based
      educational component of the Veterans Health Administration (VHA) Office of Rural
      Health Geriatric Scholars Program. It is a workforce development program to
      enhance the geriatrics knowledge and skills of VA primary care clinicians and
      staff caring for older veterans in rural communities. The RITT workshop,
      accredited for 6.5 hours, is interactive and multi-modal with didactic mini
      lectures, interactive case discussions and role play demonstrations of
      assessments. Clinic teams also develop and implement a small quality improvement
      project based on common challenges faced by older persons. This report is an
      evaluation of the effect of the RITT Program on geriatrics knowledge and team
      development as well as success in developing and implementing the quality
      improvement projects in 80 VHA rural outpatient clinics in 38 states.

PMID- 29583104
TI  - Perspectives on family caregiving of people aging with intellectual disability
      affected by dementia: Commentary from the International Summit on Intellectual
      Disability and Dementia.
AB  - This article, an output of the 2016 International Summit on Intellectual
      Disability and Dementia, examines familial caregiving situations within the
      context of a support-staging model for adults with intellectual disability (ID)
      affected by dementia. Seven narratives offer context to this support-staging
      model to interpret situations experienced by caregivers. The multidimensional
      model has two fundamental aspects: identifying the role and nature of caregiving
      as either primary (direct) or secondary (supportive); and defining how caregiving
      is influenced by stage of dementia. We propose staging can affect caregiving via
      different expressions: (1) the "diagnostic phase," (2) the "explorative phase,"
      (3) the "adaptive phase," and (4) the "closure phase." The international
      narratives illustrate direct and indirect caregiving with commonality being
      extent of caregiver involvement and attention to the needs of an adult with ID.
      We conclude that the model is the first to empirically formalize the variability
      of caregiving within families of people with ID that is distinct from other
      caregiving groups, and that many of these caregivers have idiosyncratic needs. A
      support-staging model that recognizes the changing roles and demands of carers of
      people with ID and dementia can be useful in constructing research, defining
      family-based support services, and setting public policy.

PMID- 29583105
TI  - Too old to test? Prevalence and correlates of HIV testing among sexually active
      older adults.
AB  - Older adults account for 17% of new HIV diagnoses in the US and are more likely
      to be diagnosed with HIV later in the course of the disease compared to younger
      people. We calculated the prevalence and associated factors of having ever been
      tested for HIV among sexually active older adults. We analyzed data from the 2008
      2016 General Social Survey Limited to respondents >=65 years of age who reported
      more than one sex partner(s) in past 12 months (n = 757). HIV testing prevalence,
      prevalence ratios, and 95% confidence intervals were calculated by demographic
      variables and HIV-related risk behaviors. An estimated 16.3% of sexually active
      older adults have tested for HIV, and 15.9% were at increased risk for HIV
      infection (reported injection drug and/or crack-cocaine use, exchanging money for
      sex, more than three sex partners in the past year, or men who reported having
      sex with another man). In the adjusted model, adults aged 65-70, not married,
      self-identified as gay/bisexual, and at increased risk for HIV infection were
      more likely to have tested for HIV. An estimated 83.7% of sexually active older
      adults never tested for HIV. Strategies are needed to increase HIV awareness and
      testing among potentially high-risk older adults.

PMID- 29583106
TI  - Lover and learner: Exploring relational schema change following relationship
      dissolution.
AB  - Romantic relationships are known to be very influential, but less is known about
      how these relationships, and particularly the breakup of these relationships, may
      affect individuals' relational schemas, or their expectations for relationships.
      Undergraduate students reported on how their views of themselves, romantic
      partners, and relationships changed after breaking up with a past partner.
      Results suggest that relational schemas change following relationship dissolution
      and that there are both positive and negative aspects to this change. There was
      also some evidence that aspects of the past relationship predicted change and the
      valence of change, and that change and the valence of change were related to
      aspects of current relationship quality. These results are an important first
      step in understanding how past romantic relationships influence people's
      expectations about relationships and, by extension, their health and wellbeing.

PMID- 29583107
TI  - Morphine reduces mouse microglial engulfment induced by lipopolysaccharide and
      interferon-gamma via delta opioid receptor and p38 mitogen-activated protein
      kinase.
AB  - Objective To investigate the effects of morphine on microglial phagocytosis
      during neuroinflammation. Methods C8-B4 mouse microglial cells were exposed to
      various concentrations of morphine after the stimulation with lipopolysaccharide
      and interferon-gamma and then fluorescent immunostaining was performed to assess
      the percentage of microglia that engulfed fluorescent microspheres in total
      microglia. Naloxone, beta funaltrexamine, or naltrindole was used with 1 MUM
      morphine to assess the involvement of specific opioid receptor. P38 and
      phosphorylated p38 were determined by Western blotting. A p38 mitogen-activated
      protein kinase (MAPK) activator (anisomycin 0.1 MUM) or inhibitor (SB 203580, 20
      MUM) was used to determine the involvement of p38 MAPK pathway. Results Morphine
      decreased lipopolysaccharide and interferon-gamma-induced microglial engulfment
      except the highest concentration (10 MUM) and both naloxone and naltrindole (a
      selective delta opioid receptor antagonist) attenuated morphine effect (p <
      0.001). The phosphorylated p38 was up-regulated in lipopolysaccharide and
      interferon-gamma group compared with control group (p < 0.001). This up
      regulation was decreased by 1 MUM morphine (p < 0.001). However, naltrindole
      abolished this morphine effect (p = 0.015). SB203580 blocked the increased
      microglial engulfment induced by lipopolysaccharide and interferon-gamma (p <
      0.001); whereas, anisomycin enhanced the morphine-induced decrease of engulfment
      (p < 0.001). Conclusion Morphine reduced mouse microglial engulfment induced by
      lipopolysaccharide and interferon-gamma. This morphine effect seems to be
      mediated by delta opioid receptor and via p38 MAPK inhibition.

PMID- 29583108
TI  - Bronchoscopic Improvement of Tracheobronchitis Due to Methicillin-Resistant
      Staphylococcus aureus After Aerosolized Vancomycin: A Case Series.
AB  - BACKGROUND: Ventilator-associated tracheobronchitis (VAT) is an important risk
      factor for ventilator-associated pneumonia (VAP). The efficacy of aerosolized
      vancomycin (AV) in treating VAT has not been clearly demonstrated. METHODS: Four
      mechanically ventilated patients with methicillin-resistant Staphylococcus aureus
      (MRSA) pneumonia were treated with an additional AV. AV (250 mg twice per day)
      was administered through a vibrating mesh device for 5 days. All patients were
      receiving intravenous vancomycin and had severe tracheobronchitis, based on
      bronchoscopic findings before or soon after additional AV treatment. RESULTS:
      After several days of AV treatment, follow-up bronchoscopies showed dramatic
      improvement of tracheobronchitis. All patients achieved microbiological
      eradication of MRSA. Finally, two of four patients survived through to hospital
      discharge. CONCLUSION: This case series study suggests a potential role of AV in
      the treatment of MRSA tracheobronchitis, which were accompanied by VAP. Clinical
      trial addressing the efficacy of AV in MRSA VAT and/or VAP should be needed.

PMID- 29583109
TI  - Re: "A Follow-Up Strategy for Patients with Excellent Response to Initial Therapy
      for Differentiated Thyroid Carcinoma" by Jeon et al. (Thyroid 2018;28:187-192).

PMID- 29583110
TI  - Vitamin A Supplementation by Endotracheal Application of a Nano-encapsulated
      Preparation Is Feasible in Ventilated Preterm Lambs.
AB  - BACKGROUND: Vitamin A (VA) is crucial for lung growth and development. In
      premature infants, inadequate VA levels are associated with an increased risk of
      bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown
      to decrease the incidence of BPD, but is not widely used in the clinical setting
      due to concerns about feasibility and pain. We studied VA kinetics, distribution,
      and the induction of early genetic expression of retinoid homeostatic genes in
      the lung after endotracheal and intravenous application in a preterm lamb model.
      METHODS: Lambs were delivered prematurely after 85% of gestation, intubated, and
      ventilated for 3 hours. The animals were randomized to receive no VA ("control"),
      a bolus of VA intravenously ("i.v."), or VA endotracheally directly after
      administration of surfactant ("e.t."). RESULTS: Animals treated with VA
      endotracheally directly after administration of surfactant showed significant
      increases of VA in serum and lung compared to controls. Animals treated with a
      bolus of VA intravenously showed significant increases of VA in serum, lung, and
      liver; however, peak serum concentrations and mRNA levels of homeostatic genes
      raised concerns about toxicity in this group. CONCLUSIONS: Endotracheal VA
      supplementation in preterm lambs is feasible and might offer advantages in
      comparison to i.v. Further studies are warranted to explore biological effects in
      the context of BPD.

PMID- 29583111
TI  - Conference Report: 10th Clinical Trials on Alzheimer's Disease (CTAD), Boston MA,
      USA, November 1-4, 2017.

PMID- 29583112
TI  - Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family
      Eggerthellaceae, isolated from human gut.
AB  - Urolithins are gut microbial metabolites that exert health benefits in vivo and
      are generated from ellagic acid (EA) and ellagitannin-containing foods such as
      strawberries, pomegranates and walnuts. Gordonibacter species produce some
      intermediary urolithins but the micro-organisms responsible for the
      transformation of EA into the final and more bioactive urolithins, such as
      urolithin A and isourolithin A, are unknown. We report here a new bacterium,
      capable of metabolizing EA into isourolithin A, isolated from healthy human
      faeces and characterized by determining phenotypic, biochemical and molecular
      methods. Strain CEBAS 4A belongs to the Eggerthellaceae family and differed from
      other genera of this family, both phylogenetically and phenotypically. Based on
      16S rRNA gene sequence similarity, the strain was related to Enterorhabdus
      musicola DSM 19490T (92.9 % similarity), Enterorhabdus caecimuris DSM 21839T
      (92.7 % similarity), Adlercreutzia equolifaciens DSM 19450T (92.5 % similarity),
      Asaccharobacter celatus DSM 18785T (92.5 % similarity) and Parvibacter caecicola
      DSM 22242T (91.2 % similarity). This strain was strictly anaerobic and Gram-stain
      positive. The whole-cell fatty acids were saturated (98.3 %), a very high
      percentage that differs from the nearest genera ranging from 62 to 73 %. The
      major respiratory lipoquinone was menaquinone-7 and the diamino acid in the
      peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol and
      phosphatidylglycerol comprised the main polar lipid profile in addition to
      several phosphoglycolipids (PGL1-2), phospholipids (PL1-4), glycolipids (GL1-6)
      and lipids. Based on these data, a new genus, Ellagibacter gen. nov. is proposed
      with one species, Ellagibacter isourolithinifaciens sp. nov. The type strain of
      Ellagibacter isourolithinifaciens is CEBAS 4AT (=DSM 104140T=CCUG 70284T).

PMID- 29583113
TI  - Whole-genome sequencing revealed concurrent outbreaks of shigellosis in the
      English Orthodox Jewish Community caused by multiple importations of Shigella
      sonnei from Israel.
AB  - In December 2013, Public Health England (PHE) observed an increase in the number
      of cases of Shigella sonnei linked to the Orthodox Jewish Community (OJC).
      Ultimately, 52 cases of S. sonnei phage type (PT) P and PT7 were notified between
      November 2013 and July 2014. Whole-genome sequencing (WGS) was performed on a
      HiSeq 2500 platform (Illumina) on isolates of S. sonnei submitted to PHE during
      the investigation. Quality trimmed sequence reads were mapped to a reference
      genome using BWA-MEM, and single-nucleotide polymorphisms (SNPs) were identified
      using GATK2. Analysis of the core genome SNP positions (>90 % consensus, minimum
      depth 10*, MQ>=30) revealed that isolates linked to the outbreak could be
      categorized as members of distinct monophyletic clusters (MPCs) representing
      concurrent regional outbreaks occurring in the OJCs across the United Kingdom. A
      dated phylogeny predicted the date of the most recent common ancestor of the MPCs
      to be approximately 3.1 years previously [95 % highest posterior density (HPD),
      2.4-3.4]. Isolates of S. sonnei from cases from the OJCs in Israel included in
      the phylogeny, branched from nodes basal to the UK OJC outbreak clusters,
      indicating they were ancestral to the UK OJC isolates, and that the UK isolates
      represented multiple importations of S. sonnei into the UK population from
      Israel. The level of discrimination exhibited by WGS facilitated the
      identification of clusters of isolates within the closely related bacterial
      populations circulating in the OJC that may be linked to a unique point sources
      or transmission routes, thus enabling a more appropriate public health response
      and targeted interventions.

PMID- 29583114
TI  - GlnR and PhoP regulate beta-glucosidases involved in cellulose digestion in
      response to nitrogen and phosphate availability.
AB  - The limited catalytic efficiency of cellulose-degrading enzymes restricts
      cellulose digestion. We investigated the transcriptional regulation of genes
      encoding key cellulose degrading enzymes, namely beta-glucosidases, in the
      industrial actinobacterium Saccharopolyspora erythraea. We observed that the
      expression of most beta-glucosidase-encoding genes was controlled by the
      availability of nitrogen and phosphate via their respective global regulators,
      namely GlnR and PhoP. Electrophoretic mobility shift assay demonstrated that GlnR
      and PhoP bound directly to the promoters of beta-glucosidase-encoding genes.
      Deletion of glnR resulted in lower transcript levels and activity of beta
      glucosidases, leading to decreased bacterial growth on cellulose. Overexpression
      of glnR and phoP or nitrogen/phosphate starvation increased the transcript levels
      and total activity of beta-glucosidases. Moreover, GlnR/PhoP-mediated cellobiose
      utilization was also observed in Streptomyces coelicolor A3(2). These findings
      provide insights into the regulatory roles played by GlnR and PhoP in
      coordinating nitrogen/phosphate metabolism and carbohydrate utilization, and
      indicate potential strategies for cellulose fermentation in the production of bio
      based chemicals by actinobacteria.

PMID- 29583115
TI  - DNA indicative of human bocaviruses detected in non-human primates in the
      Democratic Republic of the Congo.
AB  - Bocaparvoviruses are members of the family Parvovirinae and human bocaviruses
      have been found to be associated with respiratory and gastrointestinal disease.
      There are four known human bocaviruses, as well as several distinct ones in great
      apes. The goal of the presented study was to detect other non-human primate (NHP)
      bocaviruses in NHP species in the Democratic Republic of the Congo using
      conventional broad-range PCR. We found bocavirus DNA in blood and tissues samples
      in 6 out of 620 NHPs, and all isolates showed very high identity (>97 %) with
      human bocaviruses 2 or 3. These findings suggest cross-species transmission of
      bocaviruses between humans and NHPs.

PMID- 29583116
TI  - Lelliottia jeotgali sp. nov., isolated from a traditional Korean fermented clam.
AB  - Strain PFL01T was isolated from traditional Korean fermented clam, jogae-jeotgal,
      and characterized. The strain was a facultative anaerobic, Gram-stain-negative
      bacterium that was rod-shaped, motile and beige-pigmented. The phylogenetic
      sequence analysis based on the 16S rRNA gene from PFL01T revealed that it was
      closely related to Lelliottia nimipressuralis LMG 10245T and Lelliottia amnigena
      LMG 2784T with 99.3 and 99.3 % sequence identities, respectively. Multilocus
      sequence type analysis of concatenated partial aptD, gyrB, infB and rpoB gene
      sequences showed a clear distinction of strain PFL01T from its closest related
      type strains. The discrimination was also supported by unique repetitive
      extragenic palindromic PCR (Rep-PCR, ERIC-PCR) fingerprint patterns. In addition,
      results from average nucleotide identity analyses with other species were less
      than 85 %. vitek and API analyses revealed distinct characteristics from other
      species of Lelliottia. The cellular fatty acid profile of the strain consisted of
      C16 : 0, cyclo-C17 : 0, C16 : 1omega7c/C16 : 1omega6c and C18 : 1omega7c/C18 :
      1omega6c as major components. The whole genome of PFL01T was 4.6 Mb with a G+C
      content of 55.3 mol%. Based on these results, strain PFL01T was classified as a
      novel species of the genus Lelliottia, for which the name Lelliottia jeotgali sp.
      nov. is proposed. The type strain in PFL01T (=KCCM 43247T=JCM 31901T).

PMID- 29583118
TI  - The current state of resident trauma training: Are we losing a generation?
AB  - SUMMARY: General surgeons provide life-saving trauma care to a large portion of
      Canadians. Although trauma care has evolved significantly over the last few
      decades and now requires fewer operations, when a life-saving operation is
      required the expectation of competence to perform this operation has not been
      reduced. A recent study from the United States found decreased resident case-log
      volumes of trauma operations. Such findings raise the alarm of declining exposure
      of residents to trauma operations and beg the question of whether graduating
      residents are competent to care for trauma patients. Examination of the Canadian
      setting reveals a dearth of published information about the actual exposure of
      Canadian general surgery residents to trauma care. With the forthcoming evolution
      of general surgery education into competency-based medical education, we sound a
      call to action to ensure that all graduating general surgeons are able to provide
      the care that both the Royal College of Physicians and Surgeons of Canada and the
      Canadian public demand.

PMID- 29583117
TI  - The lytic Myoviridae of Enterobacteriaceae form tight recombining assemblages
      separated by discontinuities in genome average nucleotide identity and lateral
      gene flow.
AB  - In Bacteria, a working consensus of species circumscription may have been reached
      and one of the most prominent criteria is high average nucleotide identity (ANI).
      ANI in effect groups strains that may recombine more or less frequently,
      depending on their biology, as opposed to rare interspecies gene transfer. For
      bacteriophages, which show various lifestyles, the nature of the fundamental
      natural unit, if it exists in a biological sense, is not well understood and
      defined. The approaches based on dot-plots are useful to group similar
      bacteriophages, yet are not quantitative and use arbitrarily set cut-offs. Here,
      we focus on lytic Myoviridae and test the ANI metric for group delineation. We
      show that ANI-based groups are in agreement with the International Committee on
      Taxonomy of Viruses (ICTV) classification and already established dot-plot
      groups, which are occasionally further refined owing to higher resolution of ANI
      analysis. Furthermore, these groups are separated among themselves by clear ANI
      discontinuities. Their members readily exchange core genes with each other while
      they do not with bacteriophages of other ANI groups, not even with the most
      similar. Thus, ANI-delineated groups may represent the natural units in lytic
      Myoviridae evolution with features that resemble those encountered in bacterial
      species.

PMID- 29583119
TI  - Management of intra-abdominal vascular injury in trauma laparotomy: a South
      African experience.
AB  - BACKGROUND: Intra-abdominal vascular injury (IAVI) is uncommon but continues to
      be associated with high mortality rates despite technological advances in the
      past decades. In light of these ongoing developments, we reviewed our
      contemporary experience with IAVI in an attempt to clarify and refine our
      management strategies and the outcome of these patients. METHODS: We
      retrospectively reviewed the charts of all patients admitted between January 2011
      and December 2014 at a major trauma centre in South Africa who were found to have
      an IAVI during laparotomy for trauma. We collected demographic and clinical data
      including mechanism of injury, location and severity of the injury, concurrent
      injuries, physiologic parameters and clinical outcome. RESULTS: We identified 110
      patients with IAVIs, of whom 98 had sustained penetrating injuries (55 gunshot
      wounds and 43 stab wounds). There were 84 arterial injuries (including 21 renal
      and 17 mesenteric) and 74 venous injuries (including 21 renal and 17 inferior
      vena caval). Combined venous and arterial injuries were found in almost one-third
      of patients (34 [30.9%]). Fifty-seven patients (51.8%) required intensive care
      admission. The overall mortality rate was 28.2% (31 patients); the rate was 62%
      for aortic injuries and 47% for inferior vena cava injuries. Liver injury, large
      bowel injury, splenic injury and elevated lactate level were all associated with
      a statistically significantly higher mortality rate. CONCLUSION: The mortality
      rate for IAVI remains high despite decades of operative experience in high-volume
      centres. Open operative techniques alone are unlikely to achieve further
      reduction in mortality rates. Integration of endovascular techniques may provide
      an alternative strategy to improve outcomes.

PMID- 29583120
TI  - How early-career researchers are shaping eLife.
AB  - Initiatives to improve research communication can benefit from listening to
      graduate students, postdocs and newly-independent group leaders.

PMID- 29583121
TI  - A quinoline compound inhibits the replication of dengue virus serotypes 1-4 in
      Vero cells.
AB  - BACKGROUND: The global occurrence of dengue, a mosquito-borne viral disease
      caused by four distinct dengue viruses (DENV-1, -2, -3 and -4), is reported to
      have increased approximately 30-fold in the last 50 years, causing approximately
      400 million infections a year. A limited use, sub-optimal live attenuated dengue
      vaccine has become available recently. It is becoming apparent that antibodies to
      DENVs can promote infection by Zika virus (ZIKV), a related mosquito-borne
      flavivirus. A drug to treat these flaviviral infections continues to be an unmet
      public health need. METHODS: We screened an 'in-house' library of approximately
      2,000 small molecules for inhibitors of cloned DENV-2 protease. Putative
      inhibitor binding to DENV-2 protease was analysed by in silico docking. Anti-DENV
      activity was analysed by monitoring viral antigen synthesis by ELISA, viral RNA
      synthesis by reverse-transcription coupled to real-time polymerase chain reaction
      and infectious virus production by plaque assay, in DENV-infected Vero cells.
      RESULTS: A quinoline derivative, BT24, was identified for the first time as a
      potent inhibitor of the cloned DENV-2 protease (half maximal inhibitory
      concentration [IC50]=0.5 uM). In silico analysis revealed that BT24 binds to an
      allosteric site in the vicinity of the active site of DENV-2 protease. Cell-based
      assays demonstrated that BT24 can inhibit all four DENVs in infected Vero cells.
      CONCLUSIONS: BT24 is a DENV-2 protease inhibitor which manifests the capacity to
      inhibit the replication of all four DENVs in cultured cells. It may provide a
      lead for a pan-DENV inhibitory drug.

PMID- 29583122
TI  - Loss to follow-up and associated factors of patients in the National AIDS Program
      in Thailand.
AB  - BACKGROUND: Loss to follow-up (LTFU) is a crucial indicator to evaluate the
      effectiveness of HIV care and treatment programmes. We assessed the LTFU rate and
      associated factors of Thai HIV-infected patients who enrolled in the National
      AIDS Program (NAP) for two periods: prior to (pre-ART) and after starting ART
      (ART-patients). METHODS: Thai HIV patients aged >=15 years enrolled in NAP from
      2008 to 2014. Vital status was ascertained by linkage with the National Death
      Registry. Competing risk models were used to calculate the adjusted sub
      distribution hazards (aSHR) for LTFU for pre-ART and ART-patients, with death
      considered as a competing risk. RESULTS: A total of 157,026 patients registered
      in care and were included in analyses. The cumulative incidence of LTFU in pre
      ART patients at 1 year was 10.2%, whereas in ART-patients it was 12.8%. Among pre
      ART patients, younger age (<30 versus >=45 years, aSHR 1.60, 95% CI 1.49, 1.72),
      less advanced HIV stage (aSHR 1.29, 95% CI 1.21, 1.37) and higher CD4+ T-cell
      count (>=350 versus <100, aSHR 6.31, 95% CI 5.74, 6.95) had a higher chance of
      LTFU. ART-patients with high baseline CD4+ T-cell count (CD4 >=350 versus CD4
      <50, aSHR 2.06, 95% CI 1.97, 2.15) and non-advanced HIV stage had increased risk
      of LTFU. CONCLUSIONS: Our findings provide new evidence of the LTFU rate in Thai
      HIV-infected patients in NAP. Emphasis needs to be placed on improving follow-up
      in all patients with higher CD4+ T-cell counts. LTFU will be important to monitor
      as programmes move to commence ART regardless of CD4+ T-cell count.

PMID- 29583123
TI  - Effect of atomic disorder on the magnetic phase separation.
AB  - The effect of disorder on the magnetic phase separation between the
      antiferromagnetic and incommensurate helical [Formula: see text] and [Formula:
      see text] phases is investigated. The study is based on the quasi-two-dimensional
      single-band Hubbard model in the presence of atomic disorder (the [Formula: see
      text] Anderson-Hubbard model). A model of binary alloy disorder is considered, in
      which the disorder is determined by the difference in energy between the host and
      impurity atomic levels at a fixed impurity concentration. The problem is solved
      within the theory of functional integration in static approximation. Magnetic
      phase diagrams are obtained as functions of the temperature, the number of
      electrons and impurity concentration with allowance for phase separation. It is
      shown that for the model parameters chosen, the disorder caused by impurities
      whose atomic-level energy is greater than that of the host atomic levels, leads
      to qualitative changes in the phase diagram of the impurity-free system. In the
      opposite case, only quantitative changes occur. The peculiarities of the effect
      of disorder on the phase separation regions of the quasi-two-dimensional Hubbard
      model are discussed.

PMID- 29583124
TI  - Dynamical stability of the one-dimensional rigid Brownian rotator: the role of
      the rotator's spatial size and shape.
AB  - We investigate dynamical stability of a single propeller-like shaped molecular
      cogwheel modelled as the fixed-axis rigid rotator. In the realistic situations,
      rotation of the finite-size cogwheel is subject to the environmentally-induced
      Brownian-motion effect that we describe by utilizing the quantum Caldeira-Leggett
      master equation. Assuming the initially narrow (classical-like) standard
      deviations for the angle and the angular momentum of the rotator, we investigate
      the dynamics of the first and second moments depending on the size, i.e. on the
      number of blades of both the free rotator as well as of the rotator in the
      external harmonic field. The larger the standard deviations, the less stable
      (i.e. less predictable) rotation. We detect the absence of the simple and
      straightforward rules for utilizing the rotator's stability. Instead, a number of
      the size-related criteria appear whose combinations may provide the optimal rules
      for the rotator dynamical stability and possibly control. In the realistic
      situations, the quantum-mechanical corrections, albeit individually small, may
      effectively prove non-negligible, and also revealing subtlety of the transition
      from the quantum to the classical dynamics of the rotator. As to the latter, we
      detect a strong size-dependence of the transition to the classical dynamics
      beyond the quantum decoherence process.

PMID- 29583125
TI  - Ultrafast demagnetization at high temperatures.
AB  - Time-resolved pump-probe measurements were made at variable heat accumulation in
      Co/Pd superlattices. Heat accumulation increases the baseline temperature and
      decreases the equilibrium magnetization. Transient ultrafast demagnetization
      first develops with higher fluence in parallel with strong equilibrium thermal
      spin fluctuations. The ultrafast demagnetization is then gradually removed as the
      equilibrium temperature approaches the Curie temperature. The transient
      magnetization time-dependence is well fit with the spin-flip scattering model.

PMID- 29583126
TI  - Forming-free performance of a-SiN x :H-based resistive switching memory obtained
      by oxygen plasma treatment.
AB  - An a-SiN x -based resistive random access memory (RRAM) device with a forming
      free characteristic has significant potentials for the industrialization of the
      next-generation memories. We demonstrate that a forming-free a-SiN x O y RRAM
      device can be achieved by an oxygen plasma treatment of ultra-thin a-SiN x :H
      films. Electron spin resonance spectroscopy reveals that Si dangling bonds with a
      high density (1019 cm-3) are distributed in the initial state, which exist in the
      forms of Si2N=Si., SiO2=Si., O3=Si., and N3=Si.. X-ray photoelectron spectroscopy
      and temperature-dependent current analyses reveal that the silicon dangling bonds
      induced by the oxygen plasma treatment and external electric field contribute to
      the low resistance state (LRS). For the high resistance state (HRS), the rupture
      of the silicon dangling bond pathway is attributed to the partial passivation of
      Si dangling bonds by H+ and O2-. Both LRS and HRS transmissions obey the hopping
      conduction model. The proposed oxygen plasma treatment, introduced to generate a
      high density of Si dangling bonds in the SiN x O y :H films, provides a new
      approach to forming-free RRAM devices.

PMID- 29583127
TI  - Effects of curved midline and varying width on the description of the effective
      diffusivity of Brownian particles.
AB  - Axial diffusion in channels and tubes of smoothly-varying geometry can be
      approximately described as one-dimensional diffusion in the entropy potential
      with a position-dependent effective diffusion coefficient, by means of the
      modified Fick-Jacobs equation. In this work, we derive analytical expressions for
      the position-dependent effective diffusivity for two-dimensional asymmetric
      varying-width channels, and for three-dimensional curved midline tubes, formed by
      straight walls. To this end, we use a recently developed theoretical framework
      using the Frenet-Serret moving frame as the coordinate system (2016 J. Chem.
      Phys. 145 074105). For narrow tubes and channels, an effective one-dimensional
      description reducing the diffusion equation to a Fick-Jacobs-like equation in
      general coordinates is used. From this last equation, one can calculate the
      effective diffusion coefficient applying Neumann boundary conditions.

PMID- 29583128
TI  - Mobility gap and quantum transport in a functionalized graphene bilayer.
AB  - In a Bernal graphene bilayer, carbon atoms belong to two inequivalent sublattices
      A and B, with atoms that are coupled to the other layer by [Formula: see text]
      bonds belonging to sublattice A and the other atoms belonging to sublattice B. We
      analyze the density of states and the conductivity of Bernal graphene bilayers
      when atoms of sublattice A or B only are randomly functionalized. We find that
      for a selective functionalization on sublattice B only, a mobility gap of the
      order of 0.5 eV is formed close to the Dirac energy at concentration of adatoms
      [Formula: see text]. In addition, at some other energies conductivity presents
      anomalous behaviors. We show that these properties are related to the bipartite
      structure of the graphene layer.

PMID- 29583129
TI  - Influence of spin and charge fluctuations on spectra of the two-dimensional
      Hubbard model.
AB  - The influence of spin and charge fluctuations on spectra of the two-dimensional
      fermionic Hubbard model is considered using the strong coupling diagram
      technique. Infinite sequences of diagrams containing ladder inserts, which
      describe the interaction of electrons with these fluctuations, are summed, and
      obtained equations are self-consistently solved for the ranges of Hubbard
      repulsions [Formula: see text], temperatures [Formula: see text] and electron
      concentrations [Formula: see text] with t the intersite hopping constant. For all
      considered U the system exhibits a transition to the long-range antiferromagnetic
      order at [Formula: see text]. At the same time no indication of charge ordering
      is observed. Obtained solutions agree satisfactorily with results of other
      approaches and obey moments sum rules. In the considered region of the U-T plane,
      the curve separating metallic solutions passes from [Formula: see text] at the
      highest temperatures to U  =  2t at [Formula: see text] for half-filling. If only
      short-range fluctuations are allowed for the remaining part of this region is
      occupied by insulating solutions. Taking into account long-range fluctuations
      leads to strengthening of maxima tails, which transform a part of insulating
      solutions into bad-metal states. For low T, obtained results allow us to trace
      the gradual transition from the regime of strong correlations with the pronounced
      four-band structure and well-defined Mott gap for [Formula: see text] to the
      Slater regime of weak correlations with the spectral intensity having a dip along
      the boundary of the magnetic Brillouin zone due to an antiferromagnetic ordering
      for [Formula: see text]. For [Formula: see text] and [Formula: see text] doping
      leads to the occurrence of a pseudogap near the Fermi level, which is a
      consequence of the splitting out of a narrow band from a Hubbard subband.
      Obtained spectra feature waterfalls and Fermi arcs, which are similar to those
      observed in hole-doped cuprates.

PMID- 29583130
TI  - Static dielectric constant of water within a bilayer using recent water models: a
      molecular dynamics study.
AB  - The water confined within a surfactant bilayer is studied using different water
      models via molecular dynamics simulations. We considered four representative
      rigid models of water: the SPC/E and the TIP4P/2005, which are commonly used in
      numerical calculations and the more recent TIP4Q and SPC/epsilon models,
      developed to reproduce the dielectric behaviour of pure water. The static
      dielectric constant of the confined water was analyzed as a function of the
      temperature for the four models. In all cases it decreases as the temperature
      increases. Additionally, the static dielectric constant of the bilayer-water
      system was estimated through its expression in terms of the fluctuations in the
      total dipole moment, usually applied for isotropic systems. The estimated
      dielectric was compared with the available experimental data. We found that the
      TIP4Q and the SPC/epsilon produce closer values to the experimental data than the
      other models, particularly at room temperature. It was found that the probability
      of finding the sodium ion close to the head of the surfactant decreases as the
      temperature increases, thus the head of the surfactant is more exposed to the
      interaction with water when the temperature is higher.

PMID- 29583131
TI  - Experimental investigation and micromagnetic simulations of hybrid CoCr2O4/Ni
      coaxial nanostructures.
AB  - Multiphase CoCr2O4/Ni core-shell nanowires (NWs) have been synthesized within
      anodic aluminum oxide membranes by the combination of the sol-gel method with
      electrodeposition techniques. X-ray diffraction and x-ray photoemission
      spectroscopy results confirmed the formation of a cubic spinel structure of
      CoCr2O4 shell with space group Fd-3m (227). The morphology and composition of the
      as-grown NWs were studied by field emission scanning electron microscopy, as well
      as transmission electron microscopy. The magnetic properties of the CoCr2O4 NT
      shell and hybrid CoCr2O4/Ni NWs were measured at low temperature using a physical
      property measurement system. The temperature dependence of the magnetization
      curves showed that CoCr2O4 NTs undergo a transition from a paramagnetic state to
      a ferrimagnetic state at about 90 K and a spiral ordering transition temperature
      near 22 K. An enhanced coercivity and saturation field were observed for the
      CoCr2O4/Ni core-shell NWs compared to the single-phase Ni NWs. Micromagnetic
      simulation results indicated that there is a strong coupling between the shell
      and core layers during the magnetization reversal process. The combination of
      hard CoCr2O4 and soft Ni in a single NW structure may have potential applications
      in future multifunctional devices.

PMID- 29583132
TI  - Covalent functionalization of SWCNT with combretastatin A4 for cancer therapy.
AB  - Single walled carbon nanotubes (SWCNT) are currently under intensive
      investigation by many labs all over the world for being promising candidates for
      cancer chemotherapy delivery. On the other hand, combretastatin A4 (CA4) is an
      anticancer drug that induces cell apoptosis by inhibiting tubulin polymerization.
      However, it has the disadvantage of low water solubility and the non-selective
      targeting. Therefore, we aim to create nano-drug from the functionalization of
      SWCNT covalently with CA4 through click reaction in the presence of tetraethylene
      glycol linker in order to improve its dispersibility. Scanning electron
      microscopy and transmission electron microscopy showed good dispersibility of the
      functionalized SWCNT with diameters of 5-15 nm. Moreover, thermogravometric
      analysis showed that the efficiency of SWCNT functionalization was around 45%.
      The in vitro release profile of CA4 at physiological conditions showed that
      approximately 90% of the loaded drug was released over 50 h. After that MTS test
      was used to determine the suitable concentration range for the in vitro
      investigation of the SWCNT-CA4. After that the cytotoxic activity of the SWCNT
      CA4 was evaluated by flow cytometry using annexin V/propidium iodide (PI) test.
      In comparison with free CA4, SWCNT-CA4 treatment demonstrated a significant
      increase in necrotic cells (around 50%) at the expense of the proportion of the
      apoptotic cells. Moreover, cell cycle PI test demonstrated that free CA4 and
      SWCNT-CA4 caused G2/M arrest. However with CA4 treatment higher proportion of
      cells were in the S-phase while with SWCNT-CA4 treatment greater proportion of
      cells appeared to be in the G1-phase. Taken together, the provided data suggest
      that the novel SWCNT-CA4 has a significant anticancer activity that might be
      superior to that of free CA4.

PMID- 29583133
TI  - Magnetocrystalline anisotropy in cobalt based magnets: a choice of correlation
      parameters and the relativistic effects.
AB  - The dependence of the magnetocrystalline anisotropy energy (MAE) in MCo5 (M  = 
      Y, La, Ce, Gd) and CoPt on the Coulomb correlations and strength of spin orbit
      (SO) interaction within the GGA  +  U scheme is investigated. A range of
      parameters suitable for the satisfactory description of key magnetic properties
      is determined. We show that for a large variation of SO interaction the MAE in
      these materials can be well described by the traditional second order
      perturbation theory. We also show that in these materials the MAE can be both
      proportional and negatively proportional to the orbital moment anisotropy (OMA)
      of Co atoms. Dependence of relativistic effects on Coulomb correlations,
      applicability of the second order perturbation theory for the description of MAE,
      and effective screening of the SO interaction in these systems are discussed
      using a generalized virial theorem. Such determined sets of parameters of Coulomb
      correlations can be used in much needed large scale atomistic simulations.

PMID- 29583134
TI  - Super-resolution reconstruction of MR image with a novel residual learning
      network algorithm.
AB  - Spatial resolution is one of the key parameters of magnetic resonance imaging
      (MRI). The image super-resolution (SR) technique offers an alternative approach
      to improve the spatial resolution of MRI due to its simplicity. Convolutional
      neural networks (CNN)-based SR algorithms have achieved state-of-the-art
      performance, in which the global residual learning (GRL) strategy is now commonly
      used due to its effectiveness for learning image details for SR. However, the
      partial loss of image details usually happens in a very deep network due to the
      degradation problem. In this work, we propose a novel residual learning-based SR
      algorithm for MRI, which combines both multi-scale GRL and shallow network block
      based local residual learning (LRL). The proposed LRL module works effectively in
      capturing high-frequency details by learning local residuals. One simulated MRI
      dataset and two real MRI datasets have been used to evaluate our algorithm. The
      experimental results show that the proposed SR algorithm achieves superior
      performance to all of the other compared CNN-based SR algorithms in this work.

PMID- 29583135
TI  - 2D negative capacitance field-effect transistor with organic ferroelectrics.
AB  - In the past fifty years, complementary metal-oxide-semiconductor integrated
      circuits have undergone significant development, but Moore's law will soon come
      to an end. In order to break through the physical limit of Moore's law, 2D
      materials have been widely used in many electronic devices because of their high
      mobility and excellent mechanical flexibility. And the emergence of a negative
      capacitance field-effect transistor (NCFET) could not only break the thermal
      limit of conventional devices, but reduce the operating voltage and power
      consumption. This paper demonstrates a 2D NCFET that treats molybdenum disulfide
      as a channel material and organic P(VDF-TrFE) as a gate dielectric directly. This
      represents a new attempt to prepare NCFETs and produce flexible electronic
      devices. It exhibits a 10^6 on-/off-current ratio. And the minimum subthreshold
      swing (SS) of the 21 mV/decade and average SS of the 44 mV/decade in four orders
      of magnitude of drain current can also be observed at room temperature of 300 K.

PMID- 29583136
TI  - Electronic transport in torsional strained Weyl semimetals.
AB  - In a recent paper (Munoz and Soto-Garrido 2017 J. Phys.: Condens. Matter 29
      445302) we have studied the effects of mechanical strain and magnetic field on
      the electronic transport properties in graphene. In this article we extended our
      work to Weyl semimetals (WSM). We show that although the WSM are 3D materials,
      most of the analysis done for graphene (2D material) can be carried out. In
      particular, we studied the electronic transport through a cylindrical region
      submitted to torsional strain and external magnetic field. We provide exact
      analytical expressions for the scattering cross section and the transmitted
      electronic current. In addition, we show the node-polarization effect on the
      current and propose a recipe to measure the torsion angle from transmission
      experiments.

PMID- 29583138
TI  - Erratum: Inter-comparison of multiple statistically downscaled climate datasets
      for the Pacific Northwest, USA.
AB  - This corrects the article DOI: 10.1038/sdata.2018.16.

PMID- 29583137
TI  - [Organized physical activity in the elderly, a tool to improve physical fitness
      during ageing].
AB  - OBJECTIVE: An adequate level of fitness is critical to achieving healthy ageing.
      The aim of this study was to evaluate the impact of organized physical activity
      (PA) and the number of hours of practice on the fitness levels of the elderly.
      METHODS: A total of 3104 people over 65 years old from Spain, belonging to the
      EXERNET Multicenter Project (722 men and 2382 women, mean age: 72.1 +/- 5.3
      years) participated in the study. Fitness was evaluated by 8 specific tests for
      this population. Participation in organized PA was recorded through a
      questionnaire. Differences in fitness values depending on the participation in PA
      and the number of hours were measured with ANCOVA adjusting for age, hours of
      walking and sitting time. RESULTS: Those who did not participate in this type of
      activity increased their risk of having a low level of fitness in most variables
      evaluated, with some differences between sexes (OR: from 1.6 to 2.6 in men and
      from 1.4 to 2.2 in women). In men, no significant differences were observed
      between practicing less than 2, 2-4 or more than 4 hours (P grater than 0,05),
      with an exception in the strength of the left arm. However, women who performed
      more than 2 hours a week in organized PA had better balance, strength of lower
      and upper extremities, flexibility of lower extremities, walking speed and
      aerobic capacity than those who performed less than 2 hours of PA a week (P less
      than 0,05). CONCLUSIONS: The practice of organized PA produces a beneficial
      effect on the fitness of the elderly regardless of age, hours of walking and time
      sitting per day.

PMID- 29583139
TI  - FLO1K, global maps of mean, maximum and minimum annual streamflow at 1 km
      resolution from 1960 through 2015.
AB  - Streamflow data is highly relevant for a variety of socio-economic as well as
      ecological analyses or applications, but a high-resolution global streamflow
      dataset is yet lacking. We created FLO1K, a consistent streamflow dataset at a
      resolution of 30 arc seconds (~1 km) and global coverage. FLO1K comprises mean,
      maximum and minimum annual flow for each year in the period 1960-2015, provided
      as spatially continuous gridded layers. We mapped streamflow by means of
      artificial neural networks (ANNs) regression. An ensemble of ANNs were fitted on
      monthly streamflow observations from 6600 monitoring stations worldwide, i.e.,
      minimum and maximum annual flows represent the lowest and highest mean monthly
      flows for a given year. As covariates we used the upstream-catchment physiography
      (area, surface slope, elevation) and year-specific climatic variables
      (precipitation, temperature, potential evapotranspiration, aridity index and
      seasonality indices). Confronting the maps with independent data indicated good
      agreement (R2 values up to 91%). FLO1K delivers essential data for freshwater
      ecology and water resources analyses at a global scale and yet high spatial
      resolution.

PMID- 29583140
TI  - A Mediterranean coastal database for assessing the impacts of sea-level rise and
      associated hazards.
AB  - We have developed a new coastal database for the Mediterranean basin that is
      intended for coastal impact and adaptation assessment to sea-level rise and
      associated hazards on a regional scale. The data structure of the database relies
      on a linear representation of the coast with associated spatial assessment units.
      Using information on coastal morphology, human settlements and administrative
      boundaries, we have divided the Mediterranean coast into 13 900 coastal
      assessment units. To these units we have spatially attributed 160 parameters on
      the characteristics of the natural and socio-economic subsystems, such as extreme
      sea levels, vertical land movement and number of people exposed to sea-level rise
      and extreme sea levels. The database contains information on current conditions
      and on plausible future changes that are essential drivers for future impacts,
      such as sea-level rise rates and socio-economic development. Besides its intended
      use in risk and impact assessment, we anticipate that the Mediterranean Coastal
      Database (MCD) constitutes a useful source of information for a wide range of
      coastal applications.

PMID- 29583141
TI  - BLOND, a building-level office environment dataset of typical electrical
      appliances.
AB  - Energy metering has gained popularity as conventional meters are replaced by
      electronic smart meters that promise energy savings and higher comfort levels for
      occupants. Achieving these goals requires a deeper understanding of consumption
      patterns to reduce the energy footprint: load profile forecasting, power
      disaggregation, appliance identification, startup event detection, etc. Publicly
      available datasets are used to test, verify, and benchmark possible solutions to
      these problems. For this purpose, we present the BLOND dataset: continuous energy
      measurements of a typical office environment at high sampling rates with common
      appliances and load profiles. We provide voltage and current readings for
      aggregated circuits and matching fully-labeled ground truth data (individual
      appliance measurements). The dataset contains 53 appliances (16 classes) in a 3
      phase power grid. BLOND-50 contains 213 days of measurements sampled at 50kSps
      (aggregate) and 6.4kSps (individual appliances). BLOND-250 consists of the same
      setup: 50 days, 250kSps (aggregate), 50kSps (individual appliances). These are
      the longest continuous measurements at such high sampling rates and fully-labeled
      ground truth we are aware of.

PMID- 29583142
TI  - A database linking Chinese patents to China's census firms.
AB  - To meet researchers' increasing interest in the fast growing innovation
      activities taking place in China, we match patents filed with China's State
      Intellectual Property Office to firms covered in China's Census. China has
      experienced a strong growth in patent filings over the past two decades, and has
      since 2011 become the world's top patent filing country. China's Census database
      covers about one million unique manufacturing firms from 1998-2009, representing
      the broad Chinese economy. We design data parsing and pre-processing routines to
      clean and stem firm and assignee names, create a matching algorithm that fits
      with our data and maintains a balance between matching accuracy and workload of
      manual check, and implement a systematic manual check process to filter out false
      positives generated from computerized matching. Our project generates 1,113,588
      matches for the Census firms, among which 849,647 patents are uniquely matched.
      By creating the patent-firm linked dataset, we hope to reduce duplicative effort
      and encourage more research to better understand China's fast changing innovation
      landscape.

PMID- 29583144
TI  - Spiers Memorial Lecture. Introductory lecture: the impact of structure on
      photoinduced processes in nucleic acids and proteins.
AB  - Light is an important environmental variable and most organisms have evolved
      means to sense, exploit or avoid it and to repair detrimental effects on their
      genome. In general, light absorption is the task of specific chromophores,
      however other biomolecules such as oligonucleotides also do so which can result
      in undesired outcomes such as mutations and cancer. Given the biological
      importance of light-induced processes and applications for imaging, optogenetics,
      photodynamic therapy or photovoltaics, there is a great interest in understanding
      the detailed molecular mechanisms of photoinduced processes in proteins and
      nucleic acids. The processes are typically characterized by time-resolved
      spectroscopic approaches or computation, inferring structural information on
      transient species from stable ground state structures. Recently, however,
      structure determination of excited states or other short-lived species has become
      possible with the advent of X-ray free-electron lasers. This review gives an
      overview of the impact of structure on the understanding of photoinduced
      processes in macromolecules, focusing on systems presented at this Faraday
      Discussion meeting.

PMID- 29583145
TI  - Effective formation of stable and versatile double-stranded beta-sheets templated
      by a hydrogen-bonded duplex.
AB  - We report herein an effective approach that is generally applicable for
      constructing double-stranded beta-sheets composed of tetra- and penta-peptides
      based on a hydrogen-bonded duplex template, regardless of their amino acid
      sequences and alpha-helical or beta-sheet propensities.

PMID- 29583143
TI  - A database of the coseismic effects following the 30 October 2016 Norcia
      earthquake in Central Italy.
AB  - We provide a database of the coseismic geological surface effects following the
      Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one
      of the strongest seismic events to occur in Europe in the past thirty years,
      causing complex surface ruptures over an area of >400 km2. The database
      originated from the collaboration of several European teams (Open EMERGEO Working
      Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica
      e Vulcanologia. The observations were collected by performing detailed field
      surveys in the epicentral region in order to describe the geometry and kinematics
      of surface faulting, and subsequently of landslides and other secondary coseismic
      effects. The resulting database consists of homogeneous georeferenced records
      identifying 7323 observation points, each of which contains 18 numeric and string
      fields of relevant information. This database will impact future earthquake
      studies focused on modelling of the seismic processes in active extensional
      settings, updating probabilistic estimates of slip distribution, and assessing
      the hazard of surface faulting.

PMID- 29583149
TI  - Absolute cardiovascular risk of women using hormonal contraception in Porto-Novo.
AB  - INTRODUCTION: The purpose of this work was to determine the absolute
      cardiovascular risk (ACVR) of women using hormonal contraception in Porto-Novo.
      METHODS: We carried out a descriptive, cross-sectional study, including women at
      the time of renewal of a hormonal contraceptive method. Blood pressure, fasting
      venous blood glucose level, body mass index and electrocardiographic left
      ventricular hypertrophy were studied. The determination of ACVR was dual based on
      the World Health Organisation (WHO/ISH) and the European Society of Cardiology
      (ESC/ESH) models. RESULTS: The mean age of the women was 35.3 +/- 8.2 years.
      Blood pressure and blood glucose levels were high in 24 and 1.5% of cases,
      respectively. Left ventricular hypertrophy was present in 7.1% of cases. A high
      ACVR was found in 5.2% of these women, using the ESC/ESH model. CONCLUSION: The
      occurrence of women with high ACVR in this group raises the problem of
      cardiovascular eligibility to the contraceptive method used.

PMID- 29583150
TI  - Rheumatoid arthritis and risk of cardiovascular disease.
AB  - In developing countries, rheumatoid arthritis (RA) remains a seriously under
      prioritised disease, particularly among the underprivileged, often resulting in
      presentation of patients late in the course of their disease, further complicated
      by limited therapeutic options and inconsistent follow up. The consequences are
      often severe with irreversible disability, increased frequency of co-morbidities,
      especially cardiovascular disease (CVD), and higher mortality rates, relative to
      developed countries. Despite addressing traditional cardiovascular risk factors,
      the impact of subclinical or 'residual' inflammation from uncontrolled RA needs
      to be considered. This narrative review explores the prevalence and pathogenesis
      of CVD in RA, including the impact of tobacco use. It discusses pitfalls in the
      risk assessment of CVD in patients with RA, and the effect of disease-modifying
      anti-rheumatic therapy on cardiovascular co-morbidity.

PMID- 29583151
TI  - Ischaemic heart disease and pregnancy: the tale of two stories.
AB  - Ischaemic heart disease (IHD) is presumed to be rare in pregnancy. Based on that
      assumption, patients go undiagnosed or undertreated. IHD in pregnancy frequently
      occurs as a result of an unusual aetiology, therefore each patient needs to be
      managed individually since each may present differently. This may pose challenges
      to the consulting clinician. Pregnancy itself is a risk factor for cardiovascular
      disease, due to its associated hypercoagulable state. From current reports, the
      prevalence of IHD in females is increasing due to lifestyle changes, including
      cigarette smoking, diabetes and stress. In our modern societies, women delay
      childbearing until they are older, allowing time for risk factors to cluster.
      Although presumed to be rare in pregnant women, IHD is currently estimated to
      occur three to four times more often during pregnancy in middle- and high-income
      women, warranting an extensive review highlighting cases of IHD in pregnancy.

PMID- 29583152
TI  - Remembering the past - studies on evolution done by the genetics group at
      Universidade Federal do Rio Grande do Sul (UFRGS).
AB  - After a brief introduction about the factors that are involved in science
      development, and world and Brazilian evolutionary genetics, the studies developed
      in Porto Alegre in this area were reviewed. Four periods in the development of
      this group were distinguished: (a) Origins and first expansion (1949-1961); (b)
      Second expansion (1962-1988); (c) Third expansion (1989-2001); and (d) The last
      15 years (2002-present). The international Porto Alegre Biological Evolution
      Workshops (PABEWs), with five biannual events from 2007 o 2015, were also
      mentioned. The final message stressed the importance of the maintenance of this
      and other Brazilian groups of research through adequate finance and recognition.

PMID- 29583153
TI  - Genetic diversity and population structure of Vriesea reitzii (Bromeliaceae), a
      species from the Southern Brazilian Highlands.
AB  - The Southern Brazilian Highlands are composed by a mosaic of Mixed Ombrophilous
      Forest (MOF) and grassland formations, an interesting landscape for the study of
      population structure. We analyzed the genetic diversity within and among
      populations of the MOF-endemic bromeliad Vriesea reitzii by genotyping seven
      nuclear microsatellite loci in 187 individuals from six populations. We
      characterized levels of genetic diversity and assessed the genetic structure
      among populations. Vriesea reitzii populations showed high levels of genetic
      variation (number of alleles 28 - 43, allelic richness 3.589 - 5.531) and
      moderate levels of genetic differentiation (FST = 0.123, RST = 0.096). The high
      levels of genetic diversity may be explained by species life-history traits, such
      as habit and mating system. The moderate structure may be a product of the
      combination of ancient and contemporary gene flow, resulting from the expansion
      of the forest in the Holocene, and/or due to facilitated dispersal mediated by
      the MOF's mosaic landscape. The genetic results indicated no imminent threat to
      this bromeliad. However, the species is highly associated with the MOF, putting
      landscape conservation at the center of conservation efforts for the species'
      maintenance.

PMID- 29583154
TI  - Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR
      Cas9 when targeting the human CCR5 gene.
AB  - The human C-C chemokine receptor type-5 (CCR5) is the major transmembrane co
      receptor that mediates HIV-1 entry into target CD4+ cells. Gene therapy to knock
      out the CCR5 gene has shown encouraging results in providing a functional cure
      for HIV-1 infection. In gene therapy strategies, the initial region of the CCR5
      gene is a hotspot for producing functional gene knock-out. Such target gene
      editing can be done using programmable endonucleases such as transcription
      activator-like effector nucleases (TALEN) or clustered regularly interspaced
      short palindromic repeats (CRISPR-Cas9). These two gene editing approaches are
      the most modern and effective tools for precise gene modification. However,
      little is known of potential differences in the efficiencies of TALEN and CRISPR
      Cas9 for editing the beginning of the CCR5 gene. To examine which of these two
      methods is best for gene therapy, we compared the patterns and amount of editing
      at the beginning of the CCR5 gene using TALEN and CRISPR-Cas9 followed by DNA
      sequencing. This comparison revealed that CRISPR-Cas9 mediated the sorting of
      cells that contained 4.8 times more gene editing than TALEN+ transfected cells.

PMID- 29583155
TI  - Association between molecular markers and behavioral phenotypes in the immatures
      of a butterfly.
AB  - Newly hatched caterpillars of the butterfly Heliconius erato phyllis routinely
      cannibalize eggs. In a manifestation of kin recognition they cannibalize sibling
      eggs less frequently than unrelated eggs. Previous work has estimated the
      heritability of kin recognition in H. erato phyllis to lie between 14 and 48%. It
      has furthermore been shown that the inheritance of kin recognition is compatible
      with a quantitative model with a threshold. Here we present the results of a
      preliminary study, in which we tested for associations between behavioral kin
      recognition phenotypes and AFLP and SSR markers. We implemented two experimental
      approaches: (1) a cannibalism test using sibling eggs only, which allowed for
      only two behavioral outcomes (cannibal and non-cannibal), and (2) a cannibalism
      test using two sibling eggs and one unrelated egg, which allowed four outcomes
      [cannibal who does not recognize siblings, cannibal who recognizes siblings,
      "super-cannibal" (cannibal of both eggs), and "super non-cannibal" (does not
      cannibalize eggs at all)]. Single-marker analyses were performed using chi2 tests
      and logistic regression with null markers as covariates. Results of the chi2
      tests identified 72 associations for experimental design 1 and 73 associations
      for design 2. Logistic regression analysis of the markers found to be significant
      in the chi2 test resulted in 20 associations for design 1 and 11 associations for
      design 2. Experiment 2 identified markers that were more frequently present or
      absent in cannibals who recognize siblings and super non-cannibals; i.e. in both
      phenotypes capable of kin recognition.

PMID- 29583156
TI  - Genome-wide analysis of the Glycerol-3-Phosphate Acyltransferase (GPAT) gene
      family reveals the evolution and diversification of plant GPATs.
AB  - sn-Glycerol-3-phosphate 1-O-acyltransferase (GPAT) is an important enzyme that
      catalyzes the transfer of an acyl group from acyl-CoA or acyl-ACP to the sn-1 or
      sn-2 position of sn-glycerol-3-phosphate (G3P) to generate lysophosphatidic acids
      (LPAs). The functional studies of GPAT in plants demonstrated its importance in
      controlling storage and membrane lipid. Identifying genes encoding GPAT in a
      variety of plant species is crucial to understand their involvement in different
      metabolic pathways and physiological functions. Here, we performed genome-wide
      and evolutionary analyses of GPATs in plants. GPAT genes were identified in all
      algae and plants studied. The phylogenetic analysis showed that these genes group
      into three main clades. While clades I (GPAT9) and II (soluble GPAT) include
      GPATs from algae and plants, clade III (GPAT1-8) includes GPATs specific from
      plants that are involved in the biosynthesis of cutin or suberin. Gene
      organization and the expression pattern of GPATs in plants corroborate with clade
      formation in the phylogeny, suggesting that the evolutionary patterns is
      reflected in their functionality. Overall, our results provide important insights
      into the evolution of the plant GPATs and allowed us to explore the evolutionary
      mechanism underlying the functional diversification among these genes.

PMID- 29583157
TI  - Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational
      Retrospective Study of 1,021 Patients.
AB  - The aim of this case-case study was to determine the differences between
      dysplastic and common naevus-associated melanomas (NAM) and de novo melanomas. A
      total of 1,021 prospectively collected patients with invasive cutaneous melanoma
      from an oncology referral centre were included in the study. Of these, 75.51% had
      de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM,
      compared with de novo melanomas, were associated with intermittently photo
      exposed sites, atypical melanocytic naevi, decreased tumour thickness, and
      presence of MC1R non-synonymous variants. Common NAM were more frequent on the
      trunk and of superficial spreading type. Comparison of dysplastic with common NAM
      showed significant difference only with regard to mitoses. Both subtypes of NAM
      shared less aggressive traits than de novo melanomas, albeit with no significant
      differences in survival after multivariate adjustment. In conclusion, NAM present
      with less aggressive traits, mostly due to a greater awareness among patients of
      changing moles than due to their intrinsic biological characteristics.

PMID- 29583158
TI  - ?

PMID- 29583159
TI  - [Heart transplantation in AL amyloidosis].
AB  - Amyloidosis is a disease complex characterized by the deposition of protein
      fibrils in various tissues, which leads to structural and functional derangement
      of the affected organ. There are different types of amyloidosis categorized on
      the basis of the type of protein fibrils deposited. Cardiac involvement has been
      predominantly noted in amyloid light chain (AL) amyloidosis and is the major
      prognostic determinant and influences the therapeutic strategy.  In AL
      amyloidosis, heart transplantation is generally not recommended because of a high
      risk of recurrence in the transplanted heart and poor survival rate. However, a
      favourable outcome can be achieved if heart transplantation is followed by an
      autologous stem cell transplantation (ASCT). We describe our experience from the
      two first patients with AL amyloidosis treated with heart transplantation and
      subsequent ASCT at Sahlgrenska University Hospital.

PMID- 29583160
TI  - ?

PMID- 29583161
TI  - [New definition of and diagnostic criteria for sepsis - Swedish use of Sepsis-3].
AB  - A working group representing the Swedish Society for Infectious Diseases, the
      Swedish Society for Anaesthesiology and Intensive Care, the Swedish Society for
      Emergency Medicine, and the Swedish Intensive Care Registry have reached
      consensus on how to adopt the new sepsis definition, Sepsis-3, in Sweden. The
      recommendation is to implement the new definitions and diagnostic criteria for
      sepsis and septic shock, but not the use of the new screening tool for sepsis,
      quick-SOFA, as it needs prospective validation and since it is not clear if quick
      SOFA is more useful than the currently used general triage and early warning
      score systems. The group recommends the use of the sfollowing ICD-10 codes: R65.1
      for sepsis and R57.2 for septic shock.

PMID- 29583162
TI  - ?

PMID- 29583164
TI  - ?

PMID- 29583163
TI  - ?

PMID- 29583165
TI  - ?

PMID- 29583167
TI  - ?

PMID- 29583166
TI  - ?

PMID- 29583168
TI  - Exploring the implementation of family-witnessed resuscitation.
AB  - Cardiac arrest is a traumatic event, both for patients and their family members.
      Traditionally, healthcare professionals have often been reluctant to offer family
      members the opportunity to witness cardiopulmonary resuscitation (CPR) attempts.
      However, professional bodies globally have begun to recommend the use of family
      witnessed resuscitation (FWR) during CPR, identifying a range of potential
      benefits including supporting the patient, increasing family members' confidence
      in healthcare professionals and, in some cases, promoting acceptance of the
      patient's death. This article explores the benefits of, and barriers to, the
      implementation of FWR during CPR. Despite the perceived benefits of FWR
      identified by professional bodies, healthcare professionals, and patients and
      their families, the evidence indicates there is ongoing reluctance among some
      healthcare professionals to incorporate FWR in practice. Therefore, standardised
      global policies aimed at the multidisciplinary implementation of FWR are
      required. Additionally, multidisciplinary training and education in CPR should be
      readily available, particularly in areas where CPR is frequently used, such as
      emergency departments.

PMID- 29583169
TI  - An overview of developments in nurse prescribing in the UK.
AB  - In the UK and internationally, the nursing profession is continuing to advance
      and innovate its roles and functions. One area in which this is particularly
      notable is nurse prescribing. The UK has the most extended nurse prescribing
      rights in the world, with significant advances in this field over the past two
      decades. This article reflects on this development, what has been learned and the
      challenges that remain in relation to nurse prescribing and meeting healthcare
      service needs.

PMID- 29583170
TI  - Identification and management of drug allergy.
AB  - This article describes the signs and symptoms of drug allergy, and explains the
      effects that it can have on patient care. It outlines the risk factors for the
      development of drug allergy, along with the mechanisms by which allergic
      reactions are mediated. This article also explains the tests used to diagnose
      drug allergy, and provides recommendations for the management of patients who
      experience an allergic reaction to a drug. The author uses case studies to
      emphasise the importance of the role of the nurse in managing, reporting and
      documenting drug allergies appropriately.

PMID- 29583171
TI  - Meeting the needs of carers of people at the end of life.
AB  - Carers have a vital role in end of life care in all settings. They are essential
      in enabling people to live at home at the end of their lives. Carers give and
      receive care, and have a range of support needs related to this complex role.
      This article explores the context of caring at the end of life and considers the
      experience of carers, in particular those who have a non-professional and unpaid
      relationship with someone who is at the end of life, and the support they
      require.

PMID- 29583172
TI  - Collaborative communication: learning from advanced clinical practice patient
      consultations.
AB  - Advanced nurse practitioners, and nurses aspiring to this role, are required to
      understand how to communicate effectively and on a collaborative basis with
      patients and carers during consultations, with the aim of enhancing patient
      outcomes such as improved patient satisfaction, ability to self-manage healthcare
      needs and adherence to care plans. This article explores collaborative
      communication in consultations and how best to achieve this, using the author's
      doctoral observational research based on the findings of a mixed methods
      observational study of communication in advanced clinical practice patient
      consultations.

PMID- 29583173
TI  - [Ethical considerations when talking about addictions in adolescence].
AB  - A teenager with a problem of substance abuse or dependence to social media does
      not usually realize and tends to minimize the consequences, until the problems
      related to its use and consumption appear.  We may understand that this is a sick
      person who needs help and with full right to be assisted without any
      restrictions.  During the health care activities with these patients,
      professionals are often involved in situations in which decision-making does not
      involve just assessing health aspects, but also the legal and ethical
      implications.  Thus, we deal with some ethical issues that affect to our activity
      and the quality of care.

PMID- 29583174
TI  - [Nurse resolution for unscheduled consultations with acute minor illnesses in an
      emergency room in primary care].
AB  - Introduction: The emergency centers for primary care (CUAP, for its acronym in
      Spanish) are created in order to address low and medium emergency pathologies. 
      Nurses resolve low emergency acute minor illness, through performance algorithms
      which increase their resolutions. Objectives: The main objective is to describe
      acute minor illness in adults solved by nurses at the Manso CUAP trough
      performance algorithms. Justification: The involvement of nurses in the care for
      acute minor illness at the CUAPs strengthens their service portfolio and places
      them at the gateway of the health system.  Performance algorithms provide nurses
      with the ability to manage up to the end the resolution of the user's demand.
      Material and Method: Data collection was carried out for 6 months, during
      increased pressure flows, analyzing the use of 20 performance algorithms.  Data
      was extracted from computerized medical records. Resutls: Health problems were
      solved in 1575 patients with an average age of 40 years.  The consultations most
      frequently resolved by the nurses were: injuries (27%), application of techniques
      (20 %) and health education (13 %). Conclusions: The use of performance
      algorithms for decision-making is effective for acute minor illness nurse care. 
      Health education can solve a high performance of queries.

PMID- 29583176
TI  - Exhibition of Patients.

PMID- 29583175
TI  - [Differences in the use of health services in the Spanish adult populations].
AB  - Objective: To explore the use of health services in the Spanish population,
      according health insurance. Methods: A cross-sectional study using data from the
      Spanish National Health Survey 2011-2012 was conducted.  21 007 people were
      included.  Among individuals with health coverage, three groups were
      differentiated: people with public, private and mixed insurance.  Univariate and
      bivariate analyses were developed to know health services and bivariate analyses
      were developed to know health services use differences by health insurance.
      Results: 83.5 % of the population reported only a public coverage, 2.5 % has only
      private insurance and 14 % was enrolled in both forms.  Individuals with public
      coverage visited with higher frequency the general physician (81.9 %), while
      those with only private insurance visited a specialist in the highest proportion
      (65.6 %).  Individuals with only public health coverage presented the longest
      waiting times, for both programmed hospitalization and medical attention.  In
      general terms, people with double coverage showed the greatest participation in
      preventive activities. Conclusions: Public coverage is the most important
      coverage of the Spanish population.  Different use of health resources were
      observed according to health insurance.

PMID- 29583177
TI  - Exhibition of Instrument.

PMID- 29583178
TI  - Some Notes on Alcohol in Its Medical and Scientific Aspects.

PMID- 29583179
TI  - Clinical and Experimental Observations upon General Paralysis.

PMID- 29583181
TI  - Exhibition of Pathological Specimens.

PMID- 29583180
TI  - Article.

PMID- 29583182
TI  - Article.

PMID- 29583183
TI  - Exhibition of Patients.

PMID- 29583184
TI  - Exhibition of Patients.

PMID- 29583185
TI  - Demonstration on the Comparative Pathology of Ataxia.

PMID- 29583186
TI  - Exhibition of Patients.

PMID- 29583187
TI  - Myasthenia Gravis.

PMID- 29583189
TI  - A Series of Naked-Eye Specimens Mounted in Glycerine Jelly Illustrating the
      Pathology of Eye Diseases.

PMID- 29583188
TI  - A Microscopical Demonstration of Specimens of Actinomyces Fungus.

PMID- 29583190
TI  - Exhibition of Specimens.

PMID- 29583192
TI  - Exhibition of Instrument.

PMID- 29583191
TI  - Experiences with the Medical Department of the Army in the South African War.

PMID- 29583193
TI  - Exhibition of Patients.

PMID- 29583194
TI  - Stenosis of the Small Intestine after Strangulated Hernia.

PMID- 29583195
TI  - Exhibition of Specimens.

PMID- 29583196
TI  - Article.

PMID- 29583198
TI  - Exhibition of Pathological Specimens.

PMID- 29583197
TI  - The Edinburgh Hospital in South Africa and Its Work.

PMID- 29583200
TI  - Exhibition of Specimens.

PMID- 29583199
TI  - On a Method of Estimating the Interference with the Hepatic Metabolism Produced
      by Drugs.

PMID- 29583201
TI  - Exhibition of Apparatus.

PMID- 29583203
TI  - Exhibition of Patients.

PMID- 29583202
TI  - Demonstration on an Improved Rontgen Apparatus.

PMID- 29583204
TI  - Observations Bearing upon the Question of the Pathogenesis of General Paralysis
      of the Insane.

PMID- 29583205
TI  - On the Operations for Congenitally Misplaced and Undescended Testicle, with Notes
      of Two Cases of Congenital Deficiency of the Testicle.

PMID- 29583206
TI  - Exhibition of Patients.

PMID- 29583207
TI  - Operative Interference in Cases of Stricture of the Large Intestine.

PMID- 29583208
TI  - A Short Note on a Case of Multiple Tumours of an Unusual Type.

PMID- 29583209
TI  - Arterial Hypertonus and Arterio-Sclerosis: Their Relations and Significance.

PMID- 29583210
TI  - Demonstration of Ramsay Smith's Method of Rapidly Preparing Histological
      Specimens.

PMID- 29583211
TI  - Exhibition of Pathological Specimens.

PMID- 29583212
TI  - Suprapubic Prostatectomy.

PMID- 29583213
TI  - Demonstration of the Light Treatment of Lupus, by the Lamp Made by Messrs
      Marshall & Woods.

PMID- 29583215
TI  - Exhibition of Pathological Specimens.

PMID- 29583214
TI  - Note on Securing the Lingual Artery in Excising the Tongue through the Mouth.

PMID- 29583216
TI  - Exhibition of Patients.

PMID- 29583217
TI  - Exhibition of Patients.

PMID- 29583218
TI  - Demonstration of the Effect of the Rontgen Rays on the Bones of a Syphilitic
      Patient.

PMID- 29583220
TI  - Exhibition of Pathological Specimens.

PMID- 29583219
TI  - Exhibition of Patients.

PMID- 29583221
TI  - Exhibition of Patients.

PMID- 29583223
TI  - Exhibition of Instruments.

PMID- 29583222
TI  - Valedictory Address.

PMID- 29583225
TI  - Exhibition of Patients.

PMID- 29583224
TI  - Exhibition of Pathological Specimen.

PMID- 29583226
TI  - Exhibition of Instruments.

PMID- 29583227
TI  - A Case of Chloroma with Pathological Report, and Some Notes Descriptive of the
      Disease.

PMID- 29583228
TI  - Some Clinical Observations upon the Temperature of Phthisis Based upon Experience
      of One Hundred Consecutive Cases Treated by Open-Air Methods.

PMID- 29583229
TI  - Exhibition of Pathological Specimen.

PMID- 29583231
TI  - Notes of a Case of Chloroma and of Three Cases of Lymphatic Leukaemia.

PMID- 29583230
TI  - Haemorrhage into the Spinal Cord during Pregnancy.

PMID- 29583232
TI  - Gastro-Jejunostomy. Twenty-One Consecutive Cases Performed for Intrinsic Pyloric
      Stenosis.

PMID- 29583233
TI  - Exhibition of Pathological Specimens.

PMID- 29583234
TI  - Exhibition of Apparatus.

PMID- 29583235
TI  - Cytodiagnosis of Pleural Effusions.

PMID- 29583236
TI  - A Contribution to the Localisation of the Motor Nuclei in the Spinal Cord of Man.

PMID- 29583237
TI  - On the Co-Ordination of Medical Research in Edinburgh.

PMID- 29583238
TI  - On a Case of Jejunal Fistula.

PMID- 29583240
TI  - Exhibition of Pathological Specimens.

PMID- 29583239
TI  - A Case of Tumour of the Left Prefrontal Lobe Removed by Operation.

PMID- 29583241
TI  - Exhibition of Patients.

PMID- 29583242
TI  - Exhibition of Pathological Specimens.

PMID- 29583243
TI  - Exhibition of Patients.

PMID- 29583244
TI  - Exhibition of Patients.

PMID- 29583245
TI  - The Relative Inefficacy of Cacodylates as Therapeutic Agents.

PMID- 29583246
TI  - The Peripheral Theory of Nerve Regeneration with Special Reference to Peripheral
      Neuritis.

PMID- 29583248
TI  - Exhibition of Patients.

PMID- 29583247
TI  - On the Fallacies of the Copper Reduction Test for Sugar in the Urine.

PMID- 29583249
TI  - Exhibition of Pathological Specimens.

PMID- 29583251
TI  - Exhibition of Apparatus.

PMID- 29583250
TI  - Intra-Peritoneal Rupture of the Bladder-Notes of Two Cases, One of Which
      Recovered after Suture.

PMID- 29583253
TI  - Exhibition of Patients.

PMID- 29583252
TI  - The Treatment and Teaching of Incipient and Transient Mental Disorders in the
      Royal Infirmary.

PMID- 29583254
TI  - Exhibition of Instrument.

PMID- 29583255
TI  - Exhibition of Patients.

PMID- 29583256
TI  - Demonstration on the Comparative Pathology of Ataxia.

PMID- 29583257
TI  - Exhibition of Specimens.

PMID- 29583259
TI  - Exhibition of Specimens.

PMID- 29583258
TI  - Glaucoma and the Glaucoma Theories.

PMID- 29583260
TI  - Case of Complete Transposition of the Viscera, with Cerebral Tumour and Other
      Pathological Conditions.

PMID- 29583262
TI  - Electrical Currents of High Frequency.

PMID- 29583261
TI  - Enterectomy for Tuberculous Stricture of the Intestine.

PMID- 29583263
TI  - A Case of General Streptothrix Infection.

PMID- 29583265
TI  - Exhibition of Patients.

PMID- 29583264
TI  - Exhibition of Patients.

PMID- 29583266
TI  - On the Treatment of Various Forms of Cutaneous Disease by the X-Rays and Light.

PMID- 29583267
TI  - The Glycogen Reaction in Blood: Its Pathological and Diagnostic Import.

PMID- 29583268
TI  - The Anatomy of the Enlarged Prostate, so Far as It Bears on the Operation of
      Prostatectomy.

PMID- 29583269
TI  - Exhibition of Specimens.

PMID- 29583271
TI  - Exhibition of Specimens.

PMID- 29583270
TI  - Valedictory Address.

PMID- 29583272
TI  - Some Clinical Notes on Tuberculous Arthritis in the Young.

PMID- 29583273
TI  - Exhibition of Patients.

PMID- 29583274
TI  - Demonstration of the Surgical Anatomy of the Prostate.

PMID- 29583276
TI  - Exhibition of Patients.

PMID- 29583275
TI  - Acute Appendicitis: Its Diagnosis and the Indications for Operation.

PMID- 29583277
TI  - Exhibition of Patients.

PMID- 29583278
TI  - Exhibition of Specimens.

PMID- 29583279
TI  - Exhibition of Specimens.

PMID- 29583280
TI  - Exhibition of Specimens.

PMID- 29583281
TI  - Exhibition of Specimens.

PMID- 29583283
TI  - Exhibition of Specimens.

PMID- 29583282
TI  - Metastatic Gonorrhoeal Ophthalmia.

PMID- 29583284
TI  - Radium.

PMID- 29583285
TI  - The Open-Air-Treatment of Broncho-Pneumonia Complicating Whooping-Cough.

PMID- 29583286
TI  - Bennett's Fracture of the Base of the Metacarpal Bone of the Thumb.

PMID- 29583288
TI  - Exhibition of Patients.

PMID- 29583287
TI  - The Operative Treatment of Chronic Suppuration of the Frontal Sinus, with Special
      Reference to the Method of Killian.

PMID- 29583290
TI  - Demonstration on the Comparative Pathology of Gout.

PMID- 29583289
TI  - Exhibition of Patients.

PMID- 29583291
TI  - Exhibition of Patients.

PMID- 29583292
TI  - Exhibition of Specimens.

PMID- 29583293
TI  - Exhibition of Patients.

PMID- 29583294
TI  - Exhibition of Patients.

PMID- 29583295
TI  - On the Operative Treatments of Carcinoma of the Rectum.

PMID- 29583296
TI  - Exhibition of Specimens.

PMID- 29583297
TI  - Exhibition of Patients.

PMID- 29583298
TI  - Exhibition of Apparatus.

PMID- 29583300
TI  - Exhibition of Specimens.

PMID- 29583299
TI  - Roentgen Rays in the Diagnosis of Lung Disease.

PMID- 29583301
TI  - Exhibition of Patients.

PMID- 29583302
TI  - Retinal Haemorrhages as a Diagnostic Feature in Fracture of the Base of the Skull
      and in Subarachnoid Haemorrhage.

PMID- 29583303
TI  - Mycosis Fungoides, and Its Treatment by the X-Rays.

PMID- 29583304
TI  - Exhibition of Patients.

PMID- 29583305
TI  - Exhibition of Patients.

PMID- 29583306
TI  - Demonstration of Photographs to Draw Attention to the Value of Comparative
      Pathology in the Study of Diseases of the Nervous System.

PMID- 29583307
TI  - Lipaemia in Diabetes Mellitus.

PMID- 29583308
TI  - The Effervescing Saline Bath (Nauheim Bath) and Resistance Exercises in the
      Treatment of Heart Cases.

PMID- 29583309
TI  - A Case of Double Paralysis of the Lateral Conjugate Deviation of the Eyes.

PMID- 29583311
TI  - Exhibition of Pathological Specimens.

PMID- 29583310
TI  - On Hand Disinfection.

PMID- 29583312
TI  - Exhibition of Apparatus.

PMID- 29583313
TI  - The Scottish Medical Corporations and the Public Weal: How They Might Develop a
      Health Conscience.

PMID- 29583314
TI  - Histological Demonstration of the Skin of a Seven Months' Foetus, a Sister of the
      Ichthyosis Patients.

PMID- 29583315
TI  - Syphilis and Life Assurance.

PMID- 29583316
TI  - Gastric Hyperacidity (Hyper-Chlorhydria): Its Nature, Diagnosis, and Treatment.

PMID- 29583318
TI  - Exhibition of Instruments.

PMID- 29583317
TI  - Demonstration on the Screen of Sections of the Spinal Cord from a Case of Very
      Early Preataxic Tabes, Illustrating the Spinal Root Localisation of the Knee and
      Achillis-Jerks.

PMID- 29583319
TI  - Some Practical Suggestions in Operative Surgery.

PMID- 29583320
TI  - Exhibition of Patients.

PMID- 29583321
TI  - Exhibition of Patients.

PMID- 29583323
TI  - Exhibition of Specimens.

PMID- 29583322
TI  - The Inefficacy of Di-Sodic-Methyl-Arsenate (Arrhenal) as a Therapeutic Agent.

PMID- 29583324
TI  - Sialogogues : Their Therapeutic Employment.

PMID- 29583326
TI  - Exhibition of Patients.

PMID- 29583325
TI  - Exhibition of Specimens.

PMID- 29583328
TI  - Exhibition of Apparatus.

PMID- 29583327
TI  - Clinical and Experimental Observations upon General Paralysis.

PMID- 29583329
TI  - The Treatment of Cancer by Phototherapy.

PMID- 29583330
TI  - Exhibition of Pathological Specimens.

PMID- 29583331
TI  - Exhibition of Patients.

PMID- 29583332
TI  - A Contribution to the Study of the Local Distribution of Cancer in Scotland.

PMID- 29583333
TI  - The Prevention of Pulmonary Phthisis.

PMID- 29583335
TI  - Exhibition of Patients.

PMID- 29583334
TI  - The Onset of Fear and the Onset of Pain in Cardiac Disturbance.

PMID- 29583336
TI  - A Case of Alexia, with Autopsy.

PMID- 29583337
TI  - Remarks on the Etiology of Carcinoma: Has It a Physiological Function in the
      Body?

PMID- 29583338
TI  - A Plea for the Recognition of the Treatment of Disease by Intravenous Injections,
      with a Theory as to Action of Iodoform in Phthisis.

PMID- 29583339
TI  - Questions Regarding the Sterilisation of Dressings by Steam.

PMID- 29583341
TI  - Exhibition of Patients.

PMID- 29583340
TI  - Exhibition of Patients.

PMID- 29583342
TI  - Exhibition of Patients.

PMID- 29583343
TI  - Exhibition of Specimens.

PMID- 29583344
TI  - Exhibition of Patients.

PMID- 29583345
TI  - Exhibition of Specimens.

PMID- 29583346
TI  - A Clinical Study of Influenza in the Epidemic, 1904-5.

PMID- 29583347
TI  - Exhibition of Specimens.

PMID- 29583348
TI  - Exhibition of Specimens.

PMID- 29583349
TI  - Exhibition of Specimens.

PMID- 29583350
TI  - On the Occurrence Recently in Edinburgh and Neighbourhood of Unusual Forms of
      Cerebro-Spinal Fever and Intoxication Resembling Epidemic Cerebro-Spinal
      Meningitis.

PMID- 29583351
TI  - Considerations Relating to the Improvement of the Milk Supply, with Special
      Reference to the City of Edinburgh.

PMID- 29583352
TI  - A New Method of Performing Artificial Respiration.

PMID- 29583353
TI  - Some Remarks on Post-Anaesthetic Sickness: Its Cause and Treatment.

PMID- 29583354
TI  - Reasons for Abandoning the Uric Acid Theory of Gout.

PMID- 29583356
TI  - Exhibition of Specimens.

PMID- 29583355
TI  - The Varying Form of the Stomach.

PMID- 29583357
TI  - Bradycardia.

PMID- 29583358
TI  - The Toilet of the Anus.

PMID- 29583360
TI  - Exhibition of Specimens.

PMID- 29583359
TI  - Massage, Passive Movements, and Modified Resisted Exercises in the Treatment of
      Advanced Cardiac Dilatation.

PMID- 29583361
TI  - Syphilitic Synovitis in Children.

PMID- 29583362
TI  - Recurring Torsion of the Spermatic Cord.

PMID- 29583363
TI  - Three Cases of Word-Blindness, with Remarks.

PMID- 29583364
TI  - Exhibition of Patients.

PMID- 29583365
TI  - Exhibition of Patients.

PMID- 29583366
TI  - Microscopic Demonstration of the Effects of a Raw Meat and Water Diet on the
      Thyroid Gland of Animals.

PMID- 29583367
TI  - On the Urine Separator of Luys.

PMID- 29583368
TI  - The Pathology of Friedreich's Ataxia.

PMID- 29583369
TI  - Exhibition of Specimens.

PMID- 29583370
TI  - Exhibition of Patients.

PMID- 29583371
TI  - Exhibition of Patients.

PMID- 29583372
TI  - Demonstration of New Ligature Winders.

PMID- 29583373
TI  - The Use of Stovaine as a Spinal and Local Anaesthetic.

PMID- 29583374
TI  - Some Observations on the Use of the Opsonic Index of the Blood in the Diagnosis
      and Treatment of Pulmonary Tuberculosis.

PMID- 29583375
TI  - Occupation Mortalities.

PMID- 29583376
TI  - Exhibition of Specimens.

PMID- 29583377
TI  - Exhibition of Patients.

PMID- 29583378
TI  - Microscopic Demonstration of Micrococcus Catarrhalis from a Case of Bronchitis.

PMID- 29583379
TI  - Vaccine Treatment in Surgery.

PMID- 29583380
TI  - Vesical Tumours-Why Operative Treatment Is so Frequently Unsuccessful in Its
      Remote Curative Result. A Plea for Early Diagnosis.

PMID- 29583381
TI  - The Early Diagnosis of Glaucoma by the Screen Test-"Bjerrum's Method".

PMID- 29583383
TI  - Exhibition of Patients.

PMID- 29583382
TI  - Demonstration of Dr Klapp's System of Exercises Devised for the Treatment of
      Scoliosis.

PMID- 29583385
TI  - Ruptured Gastric Ulcer in a Boy Aged Twelve Years.

PMID- 29583384
TI  - Exhibition of Specimens.

PMID- 29583386
TI  - Exhibition of Specimens.

PMID- 29583387
TI  - Exhibition of Patients.

PMID- 29583388
TI  - Twenty-Five Consecutive Cases of Operation for Perforated Gastric and Duodenal
      Ulcers.

PMID- 29583390
TI  - Exhibition of Specimens.

PMID- 29583389
TI  - An Antidote and Emergency Case.

PMID- 29583391
TI  - Spirochaeta Pallida (Spironema Pallidum) in Syphilis.

PMID- 29583392
TI  - The Relation of Angina Pectoris and Allied Conditions to an Arterio-Cardiac
      Reflex Having Its Origin in the Abdomen.

PMID- 29583393
TI  - Rectal Alimentation.

PMID- 29583395
TI  - Exhibition of Specimens.

PMID- 29583394
TI  - Observations on Perforated Gastric and Duodenal Ulcer, Based upon a Personal
      Experience of Forty-Six Cases Operated upon.

PMID- 29583396
TI  - Exhibition of Patients.

PMID- 29583397
TI  - On the Treatment of Fractured Patella by Transverse Wiring (with a Synopsis of
      Sixteen Cases).

PMID- 29583398
TI  - The Practical Side of an Infant's Milk Depot.

PMID- 29583399
TI  - Demonstration of "Personal Experiences in the Detection of Human Blood by Means
      of the Precipitin Serum Test of Unlennuth".

PMID- 29583400
TI  - Inguinal Hernia in the Female.

PMID- 29583401
TI  - A Portable Rheostat for Use with Kirstein's Lamp for Endoscopic Examination.

PMID- 29583402
TI  - Exhibition of Specimens.

PMID- 29583403
TI  - The Medico-Chirurgical Society of Edinburgh Fifty Years Ago-Valedictory Address.

PMID- 29583404
TI  - The Method of Application of the Tonometer.

PMID- 29583406
TI  - Exhibition of Patients.

PMID- 29583405
TI  - Demonstration on the Use of the Biograph in Medicine.

PMID- 29583407
TI  - Exhibition of Specimens.

PMID- 29583408
TI  - Lantern Demonstration of "Sleeping Sickness in Uganda".

PMID- 29583409
TI  - Transient Blindness Due to Spasm of the Retinal Artery.

PMID- 29583410
TI  - Treatment of Cases of General Paralysis and Tabes Dorsalis by Vaccines and Anti
      Sera.

PMID- 29583411
TI  - Notes on Some Cases Treated by Bier's Method.

PMID- 29583412
TI  - The Electrical Conductivity of the Blood and Urine in Health and in Disease, and
      as a Test of the Functional Efficiency of the Kidney.

PMID- 29583413
TI  - Explained the Construction of the Sphygmomanometer Devised by Professor Erlanger,
      of Wisconsin University, and Afterwards Demonstrated Its Use on Some Patients in
      His Wards.

PMID- 29583414
TI  - Exhibition of Specimens.

PMID- 29583415
TI  - Exhibition of Patients.

PMID- 29583416
TI  - Microscopical Demonstration on the Effects of Oatmeal on the Thyroid Gland of
      Growing Animals.

PMID- 29583418
TI  - Exhibition of Patients.

PMID- 29583417
TI  - On the Use of the Opsonic Index in the Diagnosis of Tuberculosis.

PMID- 29583419
TI  - The Making of a Shelf below the Unduly Mobile Kidney.

PMID- 29583421
TI  - Pathological Specimens.

PMID- 29583420
TI  - Note on the Present Epidemic of Cerebro-Spinal Meningitis.

PMID- 29583422
TI  - Exhibition of Patients.

PMID- 29583423
TI  - The Naso-Pharynx as Infection Carrier in Epidemic Cerebro-Spinal Meningitis.

PMID- 29583424
TI  - The Compulsory Notification of Phthisis.

PMID- 29583425
TI  - On the Use of Massage and Movement in the Treatment of Fractures.

PMID- 29583426
TI  - Exhibition of Patients.

PMID- 29583427
TI  - The Treatment of Some Diseases Commonly Regarded as of Gouty Origin.

PMID- 29583428
TI  - Clinical Observations and Experiences in the Prognosis and Treatment of Lobar
      Pneumonia.

PMID- 29583430
TI  - Intubation of the Larynx in Laryngeal Diphtheria.

PMID- 29583429
TI  - Exhibition of Patient.

PMID- 29583431
TI  - Cerebro-Spinal Meningitis.

PMID- 29583432
TI  - Note on Two Fatal Cases of Acute Meningo-Coccal Cerebro-Spinal Meningitis in
      Young Children, with Pathological Report on One of Them.

PMID- 29583433
TI  - Exhibition of Instruments.

PMID- 29583434
TI  - The Tuberculosis Problem in Scotland.

PMID- 29583435
TI  - A Remarkable and Hitherto Undescribed Muscular Lesion Occurring in Sprue, with
      Notes of a Case of Peculiar (? Myopathic) Muscular Atrophy in Which Similar
      Changes Were Present.

PMID- 29583436
TI  - Exhibition of Patients.

PMID- 29583437
TI  - Exhibition of Specimens.

PMID- 29583438
TI  - A Plea for the Study of the Intermedio-Lateral Cell-System of the Spinal Cord.

PMID- 29583439
TI  - Epicolloid and Its Combinations, and Also Ichthyol Court Plaster.

PMID- 29583441
TI  - Exhibition of Specimens.

PMID- 29583440
TI  - On the Administration of Gas and Ethyl Chloride.

PMID- 29583442
TI  - The Differentiation of the Varieties of Extra-Systole.

PMID- 29583443
TI  - The Diagnosis and Treatment of Pancreatitis.

PMID- 29583444
TI  - Exhibition of Patients.

PMID- 29583445
TI  - Exhibition of Specimens.

PMID- 29583446
TI  - The Diagnosis and Treatment of Chronic Ulcer of the Stomach and Duodenum.

PMID- 29583447
TI  - Discussion on the Treatment of Varicose Veins of the Leg.

PMID- 29583448
TI  - Exhibition of Patients.

PMID- 29583449
TI  - Exhibition of Patients.

PMID- 29583450
TI  - The Action and Uses of Vaso-Dilators in High Blood-Pressure.

PMID- 29583451
TI  - Exhibition of Patients.

PMID- 29583452
TI  - Exhibition of Instruments.

PMID- 29583453
TI  - Exhibition of Patients.

PMID- 29583454
TI  - A Remarkable Case of Haemorrhage of the Pons-Varolii and Medulla-Oblongata.

PMID- 29583455
TI  - A Historic Instance of the Adams-Stokes Syndrome Due to Heart-Block.

PMID- 29583456
TI  - The Histology of Nasal Accessory Sinus Suppuration: A Comparison of the Simple
      Processes in the Upper Respiratory Tract, Including the Middle-Ear Clefts.

PMID- 29583458
TI  - Exhibition of Patients.

PMID- 29583457
TI  - Discussion on Oral Sepsis.

PMID- 29583460
TI  - Exhibition of Patients.

PMID- 29583459
TI  - Discussion on the Treatment of Varicose Veins of the Leg.

PMID- 29583461
TI  - The Problem of the Sane Epileptic.

PMID- 29583462
TI  - Some Results of Electrolytic Treatment and of Rontgen-Ray Diagnosis.

PMID- 29583463
TI  - On Stone-Masons' Phthisis.

PMID- 29583464
TI  - Discussion on the Symptomatology and Causes of So-Called Eye-Strain.

PMID- 29583465
TI  - A Pharmacological Estimate of the Value of Commercial Samples of the Liquid
      Extract of Ergot, with Notes on Ergot Standardisation.

PMID- 29583466
TI  - Discussion on the Artificially Prepared Hypnotics, Their Use and Possible Abuse.

PMID- 29583467
TI  - Tuberous (or Tuberose) Sclerosis.

PMID- 29583468
TI  - A Rich Protein Diet in Relation to Gout and the Thyroid Gland.

PMID- 29583469
TI  - The Differential Diagnosis and Treatment of a Common Form of Dyspepsia and of
      Early Tuberculous Infection in Children.

PMID- 29583470
TI  - The Influence of the Tissues of the Body on the Incidence and the Treatment of
      Disease. President's Valedictory Address.

PMID- 29583471
TI  - Case of Dislocation between the Atlas and the Axis Vertebrae, with Probable
      Fracture of the Odontoid Process; Reduction, Recovery.

PMID- 29583472
TI  - The Use and Possible Abuse of Athletics during the Period of Growth and
      Development.

PMID- 29583473
TI  - Syphilis and Marriage.

PMID- 29583474
TI  - Exhibition of Patients.

PMID- 29583475
TI  - Exhibition of Patients.

PMID- 29583476
TI  - Exhibition of Patients.

PMID- 29583477
TI  - Exhibition of Specimens.

PMID- 29583478
TI  - A Case Presenting Meniere's Symptoms along with Facial Paralysis.

PMID- 29583479
TI  - On the Treatment of Acute Gonorrheal Urethritis in the Male by Passive
      Hyperaemia.

PMID- 29583480
TI  - Exhibition of Patients.

PMID- 29583481
TI  - Demonstration of the Results Obtained on Bacteriological Examination for Various
      Commercial Preparations of Lactic Bacilli.

PMID- 29583482
TI  - Prostatism: A Consideration of Its Treatment, Together with Notes of the Fatal
      Cases after Prostatectomy Occurring in the Last Fifty Patients Operated upon by
      the Writer.

PMID- 29583483
TI  - Cremation and Its Advantages.

PMID- 29583484
TI  - Note on the Use of the Scopolamine-Morphine Combination as an Anaesthetic
      Adjunct.

PMID- 29583485
TI  - Demonstrated Two Sections of the Auriculo-Ventricular Bundle.

PMID- 29583486
TI  - Notes on the Effects and Use of Radium.

PMID- 29583488
TI  - Exhibition of Patients.

PMID- 29583487
TI  - The Treatment of Phthisis and Other Conditions by Arylarsonates.

PMID- 29583489
TI  - Exhibition of Specimens.

PMID- 29583491
TI  - The "Pancreatic Reaction" in Abdominal Disease.

PMID- 29583490
TI  - The Blood-Pressure in Anaesthesia.

PMID- 29583492
TI  - Exhibition of Patients.

PMID- 29583494
TI  - Exhibition of Specimens.

PMID- 29583493
TI  - Vaccine Therapy.

PMID- 29583495
TI  - Vagus Stimulation and Paresis in the Treatment of Cardiac Irregularities.

PMID- 29583496
TI  - Acute Myelocythaemia Associated with Osteosclerosis.

PMID- 29583497
TI  - Treatment of Simple Fractures.

PMID- 29583498
TI  - Tabes with Gastric Crises Improved by Section of Posterior Nerve Roots.

PMID- 29583499
TI  - Two Cases of Separate Acromion Process, with a Note on the Appearances Presented
      in Radiographs of the Acromion Process and Upper End of the Humerus during
      Ossification (Lantern Demonstration).

PMID- 29583500
TI  - Exhibition of Specimens.

PMID- 29583501
TI  - Stomach: Position of, as Guide to Pyloric or Duodenal Difficulty.

PMID- 29583502
TI  - Treatment of Tuberculous Peritonitis in Adults.

PMID- 29583503
TI  - Exhibition of Patients.

PMID- 29583504
TI  - Orthoradiography of Heart and Aorta.

PMID- 29583505
TI  - Exhibition of Patients.

PMID- 29583507
TI  - Exhibition of Patients.

PMID- 29583506
TI  - Valedictory Address.

PMID- 29583508
TI  - Exhibitions of Patients.

PMID- 29583509
TI  - Exhibition of Patients.

PMID- 29583510
TI  - The Care of the Teeth in Relation to the Health of Children at the School Ages
      The Provision of Special School Dental Clinics.

PMID- 29583511
TI  - Insufficient Data as a Cause of Faulty Interpretation of Radiographs (Lantern
      Demonstration).

PMID- 29583512
TI  - Vaccine Therapy.

PMID- 29583513
TI  - Trauma as a Factor in Disease.

PMID- 29583514
TI  - The Present Position of the Treatment of Plague.

PMID- 29583515
TI  - A Discussion on the Part Played by the Upper Air Passages as Avenues of General
      Infection.

PMID- 29583516
TI  - A Demonstration on Exercises.

PMID- 29583517
TI  - Personal Experiences in the Use of Salvarsan "606."

PMID- 29583518
TI  - The Faucial Tonsils, with Special Reference to Their Removal by Enucleation
      (Lantern Demonstration).

PMID- 29583519
TI  - Diagnosis of Urinary Calculi by Means of the X-Ray (Lantern Demonstration).

PMID- 29583520
TI  - A Case of Lymphadenoma Treated with Salvarsan.

PMID- 29583521
TI  - Exhibition of Patients.

PMID- 29583522
TI  - Exhibition of Specimens.

PMID- 29583523
TI  - Epithelioma of Tongue: Review of Sixty Hospital Cases.

PMID- 29583524
TI  - Demonstration Showing Influence of a Rich Nitrogenous Diet on the Thyroid Gland.

PMID- 29583526
TI  - Exhibition of Patients.

PMID- 29583525
TI  - Duodenal Ulcer: Its Diagnosis and Treatment.

PMID- 29583527
TI  - Exhibition of Patients.

PMID- 29583528
TI  - Exhibition of Patients.

PMID- 29583529
TI  - Arterial Pressure.

PMID- 29583531
TI  - Exhibition of Patients.

PMID- 29583530
TI  - Enlarged Prostate Associated with Vesical Tumour: Notes of Six Cases.

PMID- 29583532
TI  - Recurrent Enlargement of the Salivary Glands.

PMID- 29583533
TI  - Intestinal Obstruction and a Record of One Year-1910.

PMID- 29583534
TI  - Fungus Infection of the Finger-Nails.

PMID- 29583535
TI  - Exhibition of Patients.

PMID- 29583537
TI  - Exhibition of Specimens.

PMID- 29583536
TI  - A Local Epidemic of Acute Anterior Poliomyelitis.

PMID- 29583538
TI  - The Medical Examination of Employees.

PMID- 29583539
TI  - Exhibition of Patients.

PMID- 29583540
TI  - Large Midline Ventral Hernia, Notes on an Operation for.

PMID- 29583541
TI  - Psychotherapy.

PMID- 29583543
TI  - Ulcer, Perforated Gastric and Duodenal.

PMID- 29583542
TI  - Valedictory Address.

PMID- 29583544
TI  - Calculus in the Pelvic Portion of the Ureter, Diagnosis and Treatment of.

PMID- 29583545
TI  - Blackwater Fever, Notes on.

PMID- 29583546
TI  - Myopia, the Use of Concave Glasses for near Work in Low Degrees of.

PMID- 29583548
TI  - Exhibition of Patients.

PMID- 29583547
TI  - Tuberculosis.

PMID- 29583549
TI  - Pellagra.

PMID- 29583550
TI  - Acute Appendicitis and Acute Appendicular Obstruction.

PMID- 29583551
TI  - Encephalitis Lethargica.

PMID- 29583553
TI  - Pernicious Anaemia, Inquiry Regarding the Age and Sex Incidence of.

PMID- 29583552
TI  - Enteroptosis and Associated Conditions, Remarks on.

PMID- 29583554
TI  - Mixed Tumours of the Kidney, the Pathological Study of Embryonic So-Called "Adeno
      Sarcomata."

PMID- 29583555
TI  - Scurvy.

PMID- 29583556
TI  - Herpes and Chickenpox.

PMID- 29583557
TI  - Carcinoma of the Upper Part of the Alimentary Canal, Note on the Sex and Age
      Incidence of.

PMID- 29583558
TI  - Stammering and Its Treatment.

PMID- 29583559
TI  - Exhibition of Patients.

PMID- 29583560
TI  - Keratodermia Blenorrhagica.

PMID- 29583561
TI  - The Principle of Early Active Movement as Applied to Fractures of the Upper
      Extremity.

PMID- 29583562
TI  - Intestinal Tuberculosis.

PMID- 29583563
TI  - Bacteriurea: A Clinical Note.

PMID- 29583564
TI  - Transfusion of Blood.

PMID- 29583565
TI  - Treatment by X-Ray and Radium.

PMID- 29583566
TI  - Mesenteric Lymphadenitis.

PMID- 29583568
TI  - Physical Education in the Universities of the U.S.A.

PMID- 29583567
TI  - Physical Therapeutics.

PMID- 29583569
TI  - The Surgery of Nasal Deformities.

PMID- 29583571
TI  - On Vaccines.

PMID- 29583570
TI  - Epididymitis and Orchitis.

PMID- 29583572
TI  - Congenital Narrowing of the OEsophagus.

PMID- 29583573
TI  - Exhibition of Patients.

PMID- 29583574
TI  - Rib Pressure and the Brachial Plexus.

PMID- 29583575
TI  - Labyrinth Suppuration.

PMID- 29583577
TI  - Exhibition of Patients.

PMID- 29583576
TI  - Infectious Diseases, Discussion on Isolation and Quarantine Periods in the More
      Common.

PMID- 29583578
TI  - Empyema in Children.

PMID- 29583579
TI  - Rontgen Ray and Bismuth as an Aid in the Diagnosis of Some Alimentary Diseases.

PMID- 29583580
TI  - Ether, Note on the Intratracheal Insufflation of.

PMID- 29583581
TI  - Exhibition of Cases.

PMID- 29583582
TI  - Squamous Epithelioma of the Post-Cricoid Region, Secondarily Involving the
      Larynx, Treated by Radium, Note on a Case of.

PMID- 29583584
TI  - Edinburgh Milk Supply, Report of the Committee Appointed by the Medico
      Chirurgical Society upon the.

PMID- 29583583
TI  - Valedictory Address.

PMID- 29583585
TI  - Sclerodermia, Diffuse.

PMID- 29583586
TI  - Duodenal Ulcer, Observations on the Pathology and Etiology of.

PMID- 29583587
TI  - Exhibition of Specimen.

PMID- 29583588
TI  - Intestinal Toxaemia, Manifestations and Treatment of.

PMID- 29583589
TI  - Suprarenal Glands: Their Comparative Anatomy, Physiology, Pathology, and Relation
      to Clinical Medicine.

PMID- 29583591
TI  - Exhibition of Patients.

PMID- 29583590
TI  - Appendix, Carcinoma of the.

PMID- 29583593
TI  - Infectious Diseases, Report by the Medico-Chirurgical Society of Edinburgh on
      Isolation and Other Matters in Connection with the More Common.

PMID- 29583592
TI  - Membrane and the Genito-Mesenteric Fold of Peritoneum, Jackson's.

PMID- 29583594
TI  - X-Ray Photographs.

PMID- 29583595
TI  - Eugenic Reform, the Need for.

PMID- 29583596
TI  - Congenital Anomaly of the Urinary Apparatus Associated with Absence of Part of
      the Abdominal Wall Musculature: Report of a Case.

PMID- 29583597
TI  - Conduction Defects in the Heart (with Lantern Demonstration.).

PMID- 29583598
TI  - Exhibition of Patients.

PMID- 29583599
TI  - Cases Treated by Radium in the Royal Infirmary, Edinburgh, during 1912.

PMID- 29583600
TI  - Exhibition of Specimens.

PMID- 29583601
TI  - Exhibition of Patients.

PMID- 29583602
TI  - Multiple Neuromata of the Central Nervous System, Their Structure and
      Histogenesis.

PMID- 29583603
TI  - The Position of the Radiographer in Relation to the Physician and Surgeon.

PMID- 29583604
TI  - Bitemporal Hemiopia: Contribution to the Study of.

PMID- 29583606
TI  - Exhibition of Patient.

PMID- 29583605
TI  - Bone Tuberculosis (Adjourned Discussion).

PMID- 29583607
TI  - Bone Tuberculosis.

PMID- 29583609
TI  - Exhibition of Patients.

PMID- 29583608
TI  - Ulcer, Perforated Duodenal.

PMID- 29583610
TI  - Malingering: Discussion on.

PMID- 29583612
TI  - Ante-Mortem Thrombosis in the Right Heart and Pulmonary Arteries as a Cause of
      Death in Lobar Pneumonia.

PMID- 29583611
TI  - Nitrous Oxide and Oxygen as an Anaesthetic for Dental and Surgical Purposes.

PMID- 29583613
TI  - Exhibition of Specimen.

PMID- 29583615
TI  - Febrile Illness with Rapidly Fatal Cases: Inquiry into Outbreaks of.

PMID- 29583616
TI  - Lymphosarcoma by Radium: Notes on the Treatment of a Case of.

PMID- 29583614
TI  - Intestinal Toxaemia: Discussion on.

PMID- 29583617
TI  - Observations on the Pathology of Scrofulous Diseases, with a View to Their
      Prevention.

PMID- 29583618
TI  - Cases Which Occurred in the Practice of James Brown, Esq. Surgeon, Dominica;
      Chiefly Illustrative of Certain Morbid Preparations Presented by Him to the
      Museum of the Royal College of Surgeons of Edinburgh.

PMID- 29583619
TI  - Cases Illustrative of the Sedative Powers of the Datura Stramonium.

PMID- 29583620
TI  - On the Use of Tobacco in Tetanus.

PMID- 29583621
TI  - An Account of the Appearances Observed in the Dissection of Two of Three
      Individuals Presumed to Have Perished in the Storm of the 3d, and Whose Bodies
      Were Discovered in the Vicinity of Leith on the Morning of the 4th, November
      1821; with Some Reflections on the Pathology of the Brain: Part I.

PMID- 29583622
TI  - Contributions to the Pathology of the Heart.

PMID- 29583624
TI  - Reflections on the Pathology of the Brain: Part II.

PMID- 29583623
TI  - Cases of Infantile Disease, in Which Erosions and Perforations of the Alimentary
      Canal Were Found after Death; with Remarks.

PMID- 29583625
TI  - Case of Phrenitis with Great Cerebral Congestion, Successfully Treated in India
      by Opening the Radial Artery.

PMID- 29583627
TI  - On the Nature and Origin of Tubercular Diseases.

PMID- 29583626
TI  - History of a Case of Anaemia.

PMID- 29583628
TI  - Notice Concerning the Fever That Occurred in the Magdalene Asylum of Edinburgh,
      in the Spring of 1821, as Illustrating the Influence of Panic in Propagating
      Contagious Diseases.

PMID- 29583629
TI  - Some Observations on a Peculiar Affection to Which the Bones of the Cranium Are
      Liable.

PMID- 29583631
TI  - Case of Malformation of the Heart.

PMID- 29583630
TI  - Case of Severe Injury of the Head; with Supposed Transverse Fracture of the Base
      of the Cranium, from Which the Patient Recovered.

PMID- 29583632
TI  - Remarks on the Cranium of a Man Who Died of Syphilis, Exhibited to the Medico
      Chirurgical Society of Edinburgh.

PMID- 29583633
TI  - On Dislocation of the Hip and Shoulder Joints.

PMID- 29583634
TI  - Case of Hydrocephalus with Bifid Brain.

PMID- 29583635
TI  - Case of Purpura Haemorrhagica.

PMID- 29583636
TI  - Case of Tubercular Disease of the Peritoneum and Omentum, Combined with
      Tympanitic Affection.

PMID- 29583637
TI  - Case of Diffuse Inflammation of the Cellular Substance of the Side, Followed by a
      Series of Uncommon Symptoms, and Terminating Fatally; with the Appearances on
      Dissection.

PMID- 29583638
TI  - Case of Dysphagia, with Abscess Involving the OEsophagus, Trachea, and Lungs.

PMID- 29583639
TI  - Cases of Persons Struck by Lightning.

PMID- 29583640
TI  - Cases of Diffuse Inflammation of the Cellular Texture; with the Appearances on
      Dissection, and Observations.

PMID- 29583641
TI  - Case of Inflammation of the Cephalic Vein, Which Terminated Fatally; with the
      Appearances on Dissection.

PMID- 29583642
TI  - On Melanosis.

PMID- 29583643
TI  - Observations on the Effects of the Sun's Rays on the Human Body.

PMID- 29583644
TI  - On a New Method of Preserving Anatomical Preparations.

PMID- 29583645
TI  - Additional Cases and Observations Illustrating the Origin of Tubercles.

PMID- 29583646
TI  - Supplement to the Obstruction of the Canals of the Arteries, Containing Two Cases
      of Laceration of the Popliteal Artery from Dislocation of the Knee-Joint.

PMID- 29583647
TI  - Case of Disease of the Heart.

PMID- 29583649
TI  - On a Remarkable Alteration in the Structure of the Patella, Produced Apparently
      by the Presence of a Loose Cartilage within the Cavity of the Knee-Joint.

PMID- 29583648
TI  - On the Sudden Spontaneous Obstruction of the Canals of the Larger Arteries of the
      Body; with Some Observations on the Process Employed by Nature to Prevent or
      Arrest Haemorrhage from Lacerated Arteries.

PMID- 29583650
TI  - Observations on Hospital Gangrene, with Reference to the Disease Chiefly as It
      Appeared in the British Army during the Late War in the Peninsula.

PMID- 29583651
TI  - Case of Strangulated Umbilical Hernia; in Which the Operation Was Performed with
      Success.

PMID- 29583652
TI  - Case of Aneurism of the Aorta, with Disease of the Spinal Cord, and Some
      Anomalous Symptoms.

PMID- 29583653
TI  - Notice of Some Remarkable Morbid Appearances in a Skull, Exhibited to the Medico
      Chirurgical Society of Edinburgh.

PMID- 29583654
TI  - Case in Which a Polypus of Great Size Was Removed from the Root of the Tongue by
      Ligature.

PMID- 29583655
TI  - On the Viscera of the Common Swordfish, (Xiphias Gladius, Lin.).

PMID- 29583656
TI  - Observations on the Natural or Spontaneous Cure of Syphilis.

PMID- 29583657
TI  - Observations on the Causes of the Sounds Produced by the Action of the Heart.

PMID- 29583658
TI  - Case of a Congenital Disease, or Malformation of the Thigh-Bone; Illustrating the
      Pathology of Interstitial Absorption of the Cervix Femoris.

PMID- 29583659
TI  - Remarkable Case of Crural Hernia.

PMID- 29583660
TI  - Notes of Some Remarkable Cases.

PMID- 29583661
TI  - Observations on the Prevailing Opinions Respecting Respiration and Animal Heat,
      with Experiments.

PMID- 29583662
TI  - Case of Carditis, Attended by Unusual Symptoms, with an Account of the
      Appearances on Dissection; Death Having Occurred from Another Cause, after the
      Cure of the Original Disease.

PMID- 29583663
TI  - Case of Mollities Ossium, with the Appearances on Dissection.

PMID- 29583664
TI  - Description of a Monster, in Whom the Upper and Lower Extremities Were Entirely
      Awanting.

PMID- 29583665
TI  - Description of Two Children United Together, and Now Living in the Village of
      Arasoor, in the District of Bhavany.

PMID- 29583666
TI  - Additional Observations on the Use of Tobacco in Tetanus.

PMID- 29583667
TI  - Case in Which a Calculus of Considerable Size Was Extracted from the Female
      Bladder, by Gradual Dilatation of the Urethra.

PMID- 29583668
TI  - Case of the High Operation of Lithotomy, in Which Unusual Difficulty Was
      Experienced in the Extraction of the Stone.

PMID- 29583669
TI  - Case of Extraction of Calculus from the Female Bladder, by Dilatation of the
      Urethra.

PMID- 29583670
TI  - Observations on Cutaneous Absorption, with Experiments.

PMID- 29583671
TI  - Case of Empyema, Successfully Treated by Paracentesis Thoracis.

PMID- 29583672
TI  - An Account of Several Cases of Poisoning with Arsenic, in Illustration of the
      Delicacy of the Chemical Evidence, and Weight of the Evidence Drawn from
      Symptoms.

PMID- 29583673
TI  - Observations on the Nature, Causes and Treatment of Beriberi.

PMID- 29583675
TI  - Case of Purpura Haemorrhagica, Terminating Fatally, with the Appearances on
      Dissection.

PMID- 29583674
TI  - Case of Hydrocephalus Chronicus, with Some Unusual Symptoms and Appearances on
      Dissection.

PMID- 29583676
TI  - Observations on Gunshot Wounds of the Extremities, Illustrated by a Case.

PMID- 29583678
TI  - Observations on Chronic Inflammation of the Iris.

PMID- 29583677
TI  - Case of Chronic Gastritis.

PMID- 29583679
TI  - Account of the Yellow Fever, as It Appeared in the Queen's Regiment, in
      Barbadoes, in 1816 and 1817.

PMID- 29583680
TI  - Case in Which the Stomach of an Infant Terminated in a Cul De Sac.

PMID- 29583682
TI  - Cases Illustrating the Contagious Nature of Erysipelas, and Its Connection with a
      Severe Affection of the Throat.

PMID- 29583681
TI  - On the Use of a New Substance, Silk-Worm Gut, for Securing Divided Arteries.

PMID- 29583684
TI  - Case of Disorganization of the Stomach of an Infant, with Pathological and
      Practical Remarks; Intended as Supplementary to a Former Paper on the Same
      Subject.

PMID- 29583683
TI  - Observations on the Dysentery of Madeira.

PMID- 29583685
TI  - Observations on the Physiological Principle of Sympathy, Chiefly in Reference to
      the Peculiar Doctrines of Mr Charles Bell.

PMID- 29583686
TI  - Account of the Exanthematous Ophthalmia, with Observations on Its Treatment.

PMID- 29583687
TI  - Exhibition of Pathological Specimens.

PMID- 29583688
TI  - Exhibition of Patient.

PMID- 29583689
TI  - Ankle Clonus in Relation to the Height of the Individual.

PMID- 29583690
TI  - Exhibition of Specimens.

PMID- 29583691
TI  - Exhibition of Specimens.

PMID- 29583692
TI  - Acute Circumscribed Cutaneous OEdema.

PMID- 29583694
TI  - Exhibition of Pathological Specimens.

PMID- 29583693
TI  - Exhibition of Patient.

PMID- 29583695
TI  - The Treatment of Diphtheritic Sore Throat.

PMID- 29583697
TI  - Exhibition of Patients.

PMID- 29583696
TI  - Unusual Case of Strangulated Congenital Hernia.

PMID- 29583699
TI  - Exhibition of Patients.

PMID- 29583698
TI  - Nutrition and Reproduction: Considered Generally, and as Bearing on the Etiology
      and Treatment of Disease.

PMID- 29583700
TI  - Exhibition of New Instruments.

PMID- 29583701
TI  - On a Form of Loss of Memory Occasionally Following Cranial Injuries.

PMID- 29583702
TI  - Case of Strangulated Congenital Inguinal Hernia.

PMID- 29583703
TI  - Tumour of the Left Temporo-Sphenoidal Lobe, the Symptoms of Which Closely
      Simulated Hysteria.

PMID- 29583704
TI  - Exhibition of Pathological Specimens.

PMID- 29583705
TI  - Germs and the Spray.

PMID- 29583706
TI  - Medical Notes and Statistics of the British Expedition to Egypt in 1801.

PMID- 29583708
TI  - Sequelae of Tracheotomy Occurring after Closure of the Tracheal Wound.

PMID- 29583707
TI  - Note on the Treatment of Warts on the Genitals by Chromic Acid.

PMID- 29583709
TI  - Exhibition of Pathological Specimens.

PMID- 29583711
TI  - Case of Difficult Labour; Metro-Peritonitis; Carbolic Acid Poisoning on Fifth
      Day; Severe General Serous Inflammations; Death. With Report to Procurator
      Fiscal.

PMID- 29583710
TI  - Note of a Somewhat Unusual and Complicated Case of Inguinal Hernia.

PMID- 29583712
TI  - Exhibition of Specimen.

PMID- 29583713
TI  - Notes on Two Uncommon Forms of Ear Disease.

PMID- 29583714
TI  - Note on the Position and Mechanism of the Haemic Murmur.

PMID- 29583715
TI  - The Causes of Tinnitus Aurium.

PMID- 29583717
TI  - Exhibition of Specimens.

PMID- 29583716
TI  - The Treatment of Syphilis.

PMID- 29583719
TI  - Exhibition of Patients and Specimens.

PMID- 29583718
TI  - The Murmurs of Debility in the Pulmonary and Tricuspid Areas.

PMID- 29583721
TI  - Exhibition of Specimens.

PMID- 29583720
TI  - Note on Rupture of the Urethra, and Its Treatment.

PMID- 29583722
TI  - An Accidental Experiment with Antiseptics.

PMID- 29583723
TI  - Exhibition of Specimens.

PMID- 29583724
TI  - Alternation, Periodicity, and Relapse in Mental Diseases.

PMID- 29583725
TI  - Exhibition of Specimens.

PMID- 29583726
TI  - Exhibition of Specimens.

PMID- 29583727
TI  - A Case of Diabetic Coma with Lipaemia.

PMID- 29583728
TI  - Cranial Injuries.

PMID- 29583729
TI  - An Accidental Experiment with Antiseptics.

PMID- 29583731
TI  - Exhibition of Specimens.

PMID- 29583730
TI  - On the Treatment of Fresh Wounds.

PMID- 29583732
TI  - Some of the Sequelae of Acute Infectious Diseases in Children.

PMID- 29583733
TI  - Cases of Stricture of the Urethra.

PMID- 29583734
TI  - Arguments in Favour of the Theory of Dilatation of the Heart as the Cause of
      Cardiac Haemic Murmurs, and of the Appendix of the Left Auricle Being the Primary
      Seat of This Murmur.

PMID- 29583735
TI  - Note on the Anatomy of the Pia Mater.

PMID- 29583736
TI  - Case of Intestinal Obstruction Treated by Opening the Abdomen.

PMID- 29583737
TI  - On a Rare Form of Senile Gangrene.

PMID- 29583739
TI  - Exhibition of Specimens.

PMID- 29583738
TI  - Exhibition of Specimens, Etc.

PMID- 29583740
TI  - Valedictory Address by the Retiring President.

PMID- 29583741
TI  - The Action of the Auricles in Health and Disease.

PMID- 29583742
TI  - On Hereditary Transmission of Disease.-Method of Graphic Representation.

PMID- 29583743
TI  - An Account of Some Experiments on Different Parts of the Human Body.

PMID- 29583744
TI  - Observations on the Temperature of the Human Body after Death.

PMID- 29583745
TI  - Observations on Painful Subcutaneous Tubercle, with Cases and Histories of the
      Disease.

PMID- 29583746
TI  - On Painful Subcutaneous Tubercle, Being a Supplement to a Former Communication on
      That Subject.

PMID- 29583747
TI  - Observations on Neuroma, with Cases and Histories of the Disease.

PMID- 29583748
TI  - Cases in Which Poisonous Effects Were Produced by Swallowing the Seeds of the
      Datura Arborea.

PMID- 29583749
TI  - Account of a Contagious Epidemic Disease, Which Made Its Appearance in the Island
      of St Croix, West Indies, in the Month of October 1827.

PMID- 29583750
TI  - Remarks on Stricture, with Three Cases of Stricture of the OEsophagus.

PMID- 29583751
TI  - Case of Emphysema, without Local Injury.

PMID- 29583752
TI  - Case of Extra Uterine Foetation, Connected with Retroversio Uteri.

PMID- 29583753
TI  - Case of Aneurism of the Aorta, Terminating by Rupture into the OEsophagus.

PMID- 29583754
TI  - Observations on James's Powder, and the Antimonial Powder of the London
      Pharmacopoeia.

PMID- 29583755
TI  - Memoir of the Diseases of the British Troops during the Burman War.

PMID- 29583756
TI  - Some Account of a Cerebral Affection, as Arising during the Course of Pulmonary
      Consumption, and Arresting the Future Progress of That Fatal Disease.

PMID- 29583757
TI  - On the Effects of Removing Atmospheric Pressure from the Fluids and Solids of the
      Human Body.

PMID- 29583758
TI  - Observations on the Use of Secale Cornutum, (Ergot of Rye), in Cases of Tedious
      Labour.

PMID- 29583760
TI  - Exhibition of Instruments.

PMID- 29583759
TI  - On the Deleterious Effects of the Smoke of Coal, as Illustrated in the Cases of
      Six Individuals Subjected to Its Influence.

PMID- 29583762
TI  - Exhibition of Patient.

PMID- 29583761
TI  - The Early Stages of Tuberculosis.

PMID- 29583763
TI  - Exhibition of Other Specimens.

PMID- 29583765
TI  - Exhibition of Patients.

PMID- 29583764
TI  - Catheter Fever.

PMID- 29583766
TI  - Exhibition of Pathological Specimens.

PMID- 29583768
TI  - Wound Treatment without the Spray.

PMID- 29583767
TI  - Valedictory Address by the Retiring President.

PMID- 29583769
TI  - Clinical Observations on a Case of Perforating Gastric Ulcer.

PMID- 29583770
TI  - Exhibition of Patients.

PMID- 29583771
TI  - Exhibition of Pathological Specimens.

PMID- 29583773
TI  - On Some Points of Importance in Medical Practice.

PMID- 29583772
TI  - Exhibition of Pathological Specimens.

PMID- 29583774
TI  - Traumatic Stricture: Its Treatment by Supra-Pubic Cystotomy.

PMID- 29583775
TI  - Exhibition of Pathological Specimens.

PMID- 29583776
TI  - Case of Malformation in a Male Child, in Which the Rectum Ended in the Membranous
      Portion of the Urethra, and the Faeces Were Passed through the Penis.

PMID- 29583777
TI  - On the Early Publications of the Medico-Chirurgical Society of Edinburgh.

PMID- 29583779
TI  - Exhibition of Microscopical Sections and Drawings.

PMID- 29583778
TI  - On a Case of Patent Ductus Arteriosus, with Aneurism of the Pulmonary Artery.

PMID- 29583780
TI  - On the Fold of the Nates.

PMID- 29583781
TI  - A Rare Form of Laryngeal Neurosis.

PMID- 29583782
TI  - Five Cases of Amputation at the Hip-Joint.

PMID- 29583783
TI  - Exhibition of Pharmaceutical Specimens.

PMID- 29583784
TI  - A Case of Addison's Disease at an Unusually Early Age, with Descriptions of
      Microscopic Sections of the Supra-Renal Capsules.

PMID- 29583785
TI  - Exhibition of Pathological Specimens.

PMID- 29583786
TI  - Tonsillar Disease in Children.

PMID- 29583787
TI  - Exhibition of Pathological Specimens.

PMID- 29583788
TI  - Germs and the Spray.

PMID- 29583789
TI  - Exhibition of Instruments.

PMID- 29583790
TI  - Exhibition of Pathological Specimens.

PMID- 29583791
TI  - Exhibition of Pathological Specimens.

PMID- 29583792
TI  - Exhibition of Patients.

PMID- 29583793
TI  - Exhibition of Pathological Specimens.

PMID- 29583794
TI  - A Demonstration of Some of the Methods of Cultivating Micro-Organisms.

PMID- 29583796
TI  - The Cessation of Respiration under Chloroform, and Its Restoration by a New
      Method.

PMID- 29583795
TI  - Chronic Poisoning by Bisulphide of Carbon.

PMID- 29583798
TI  - Exhibition of Patients.

PMID- 29583797
TI  - On a Tumour of the Testicle.

PMID- 29583799
TI  - Exhibition of Pathological Specimens.

PMID- 29583800
TI  - Exhibition of Patients.

PMID- 29583801
TI  - A Case of Poisoning with Nitrate of Potash, with Hints as to the Conduct of
      Medical Practitioners in Cases of Suspected Poisoning.

PMID- 29583802
TI  - Exhibition of Pathological Specimens.

PMID- 29583804
TI  - Exhibition of Pathological Specimens.

PMID- 29583803
TI  - Case of Empyaema, with Operation for Closure of Pleural Cavity by Removing
      Portions of Four Ribs.

PMID- 29583806
TI  - Exhibition of Patients.

PMID- 29583805
TI  - Exhibition of Pathological Specimens.

PMID- 29583807
TI  - Exhibition of Instruments.

PMID- 29583809
TI  - Clinical and Pathological Demonstrations.

PMID- 29583808
TI  - Case in Which a Loud Splashing Sound Was Produced Synchronously with Cardiac
      Action.

PMID- 29583810
TI  - A Female from whom a Fatty and Fibro-Cellular Tumour of the Right Parotid Gland
      had been removed: Exhibited by Mr. Joseph Bell.

PMID- 29583812
TI  - The External Auditory Meatus in the Child.

PMID- 29583811
TI  - On the Danger of Neglecting, and on the Best Means of Controlling the Febrile
      State.

PMID- 29583813
TI  - Exhibition of Patients.

PMID- 29583814
TI  - Exhibition of Pathological Specimens.

PMID- 29583815
TI  - On Some Injuries Implicating the Elbow-Joint.

PMID- 29583816
TI  - Exhibition of Patients.

PMID- 29583817
TI  - On the Innervation of the Bronchi.

PMID- 29583818
TI  - The Position of the Medical Profession in Regard to Certificates of Mental
      Unsoundness and Civil Incapacity.

PMID- 29583819
TI  - That the Lateral Movement of the Ulna in Pronation and Supination Takes Place at
      the Shoulder-Joint.

PMID- 29583820
TI  - The Etiology of Rickets.

PMID- 29583821
TI  - On a Case of Tapping of the Pericardium, and on Tapping of the Pleura in the
      Treatment of Cardiac Disease.

PMID- 29583822
TI  - Exhibition of Specimens.

PMID- 29583824
TI  - Exhibition of Pathological Specimen and Chart.

PMID- 29583823
TI  - An Operation for Displaced Semilunar Cartilage.

PMID- 29583825
TI  - Exhibition of New Remedy.

PMID- 29583826
TI  - Exhibition of Drawings and Pathological Specimens.

PMID- 29583827
TI  - The Place of Specialism in General Practice, with Reference to Diseases of the
      Eye, Ear, and Throat.

PMID- 29583829
TI  - Exhibition of Patient.

PMID- 29583828
TI  - On the Position of the Empty and Distended Bladder in the Male Child.

PMID- 29583830
TI  - Exhibition of Instruments, Etc.

PMID- 29583831
TI  - Ovariotomy in a County Hospital, with a Note on a Method of Preparation of Cysts
      for Exhibition.

PMID- 29583832
TI  - Some Local Causes of Foetid Breath.

PMID- 29583833
TI  - Exhibition of New Surgical Appliance.

PMID- 29583835
TI  - Exhibition of Microscopic Sections and Drawings.

PMID- 29583834
TI  - Clinical Note on an Instance of Hereditary Herpes Zoster.

PMID- 29583836
TI  - Nutrition and Growth in Connexion with Pulmonary Phthisis.

PMID- 29583837
TI  - Exhibition of Patients.

PMID- 29583838
TI  - Exhibition of Instrument.

PMID- 29583839
TI  - A Contribution to the Study of Laryngeal Paralysis.

PMID- 29583841
TI  - Exhibition of Patients.

PMID- 29583840
TI  - On Cheyne-Stokes Respiration.

PMID- 29583842
TI  - Exhibition of Specimens.

PMID- 29583843
TI  - A Case of Tubercular Ulceration of the Bladder, with Unusual Clinical History.

PMID- 29583844
TI  - The Minute Anatomy of the Placenta in Extra-Uterine Gestation.

PMID- 29583845
TI  - Artificial Legs. Part II. Sites for Amputation in the Lower Limb in Relation to
      Artificial Substitutes.

PMID- 29583847
TI  - Exhibition of Patients.

PMID- 29583846
TI  - Note on a Case of Elephantiasis Arabum.

PMID- 29583848
TI  - Hospital Experiences Part I.

PMID- 29583849
TI  - Exhibition of Specimens.

PMID- 29583850
TI  - On the Removal of Naso-Pharyngeal Tumours.

PMID- 29583851
TI  - Exhibition of Pathological Specimens.

PMID- 29583852
TI  - Exhibition of Patient.

PMID- 29583853
TI  - Exhibition of Pathological Specimen.

PMID- 29583854
TI  - Exhibition of Pathological Specimens.

PMID- 29583855
TI  - Exhibition of Drawings.

PMID- 29583856
TI  - Exhibition of Instruments.

PMID- 29583857
TI  - Two Suggestions for Improving the Operation of Excision of the Knee-Joint for
      Strumous Disease.

PMID- 29583858
TI  - The Surgical Treatment of Empyema.

PMID- 29583859
TI  - Exhibition of Pathological Specimens, Etc.

PMID- 29583860
TI  - The Treatment of Diphtheria in Children by Steam Medicated with Sulphurous Acid.

PMID- 29583861
TI  - Exhibition of Specimens.

PMID- 29583862
TI  - The Care of Habitual Drunkards.

PMID- 29583863
TI  - Case of Gangrene of the Transverse Colon in an Umbilical Hernia; Removal of 22
      Inches of Gut; Suture of the Intestines; Recovery.

PMID- 29583864
TI  - Pleurisy and Pleuritic Effusion from the Anatomico-Physiological Standpoint.

PMID- 29583865
TI  - Exhibition of Patients.

PMID- 29583866
TI  - Case of Acute Intussusception in a Child 3 Years of Age, Successfully Relived by
      Abdominal Section.

PMID- 29583867
TI  - Clinical Notes on Fatty Tumours of the Larynx.

PMID- 29583868
TI  - Exhibition of Pathological Specimens.

PMID- 29583869
TI  - Intestinal Obstruction: Its Pathology and Treatment, Medical and Surgical.

PMID- 29583870
TI  - On the Only Way of Raising the Tongue, the Epiglottis, and the Aryteno-Epiglottic
      Folds at One and the Same Time.

PMID- 29583871
TI  - Notes on Report of the Departmental Committee Appointed to Inquire into Pleuro
      Pneumonia and Tuberculosis in the United Kingdom.

PMID- 29583873
TI  - Exhibition of Patient.

PMID- 29583872
TI  - On Strumous Glands.

PMID- 29583874
TI  - Exhibition of Patients.

PMID- 29583875
TI  - Exhibition of Patients.

PMID- 29583877
TI  - Exhibition of Specimens.

PMID- 29583876
TI  - Exhibition of Apparatus.

PMID- 29583878
TI  - Clinical Remarks upon the Operative Surgery of the Male Bladder.

PMID- 29583879
TI  - Exhibition of Pathological Specimen.

PMID- 29583880
TI  - The Diagnosis of Early Phthisis by the Microscope.

PMID- 29583881
TI  - Exhibition of Instruments.

PMID- 29583882
TI  - Exhibition of Patient.

PMID- 29583883
TI  - Methods of Treating Nasal and Naso-Pharyngeal Polypi.

PMID- 29583884
TI  - Exhibition of Specimens.

PMID- 29583885
TI  - Exhibition of Patient.

PMID- 29583886
TI  - Valedictory Address by the Retiring President.

PMID- 29583887
TI  - Empyema of the Superior Maxillary Antrum with Only Nasal Symptoms.

PMID- 29583888
TI  - The Treatment of Fibroid Tumours of the Uterus by Electricity.

PMID- 29583889
TI  - Exhibition of Patients.

PMID- 29583891
TI  - Exhibition of Specimens.

PMID- 29583890
TI  - A Method of Applying Capillary Drainage for the Removal of Thin Fluids.

PMID- 29583893
TI  - Exhibition of Patients.

PMID- 29583892
TI  - Tracheotomy in Children, Why Unsuccessful?

PMID- 29583894
TI  - Artificial Legs: Part I. Should Partial Foot Amputation be Abandoned?

PMID- 29583895
TI  - A Case of Cerebral Injury from a Fall.

PMID- 29583896
TI  - Three Cases of Nephrotomy, with Remarks.

PMID- 29583897
TI  - The Clinical Value of Temperature Observations in Some Acute and Chronic
      Diseases.

PMID- 29583898
TI  - Two Epidemics of Sore Throat and Their Relation to the Milk Supply.

PMID- 29583899
TI  - The Place of Specialism in General Practice, with Reference to Diseases of the
      Eye, Ear, Throat, and Naso-Pharynx.

PMID- 29583900
TI  - Exhibition of Patient.

PMID- 29583901
TI  - On the Etiology of Tumours: Abstract of Remarks Opening the Discussion.

PMID- 29583902
TI  - Animal Tuberculosis in Relation to Consumption in Man.

PMID- 29583903
TI  - Tropical Malaria and Its Sequelae.

PMID- 29583904
TI  - Exhibition of Patient.

PMID- 29583905
TI  - A Case of Multiple Neuritis in a Woman, of Combined Syphilitic and Alcoholic
      Origin; Treatment by Electro-Massage; Complete Recovery.

PMID- 29583906
TI  - Exhibition of Surgical Appliance.

PMID- 29583907
TI  - A Method of Applying Syphon Exhaustion to Cases of Empyaema.

PMID- 29583908
TI  - On Certain Physiological Variations in the Shape and Position of the Liver.

PMID- 29583909
TI  - Exhibition of Specimens.

PMID- 29583910
TI  - On the Cure of Facial Neuralgia, Odontalgia, and Allied Neuroses.

PMID- 29583912
TI  - Exhibition of Specimens.

PMID- 29583911
TI  - Case of Intestinal Obstruction Successfully Treated by Laparotomy.

PMID- 29583913
TI  - Fat Herniae in the Inguinal Region.

PMID- 29583914
TI  - Tetanoid Convulsions in an Infant; Operation; Recovery.

PMID- 29583915
TI  - Exhibition of Patients.

PMID- 29583916
TI  - On Influenza.

PMID- 29583917
TI  - The Electric Cystoscope.

PMID- 29583918
TI  - On the Pathology and Successful Treatment of Chronic Tropical Diarrhoea (Known as
      Sprue).

PMID- 29583919
TI  - Motor Paralysis Resulting from the Hypodermic Injection of Ether.

PMID- 29583920
TI  - Croupous Pneumonia in Children.

PMID- 29583921
TI  - Exhibition of Patients.

PMID- 29583922
TI  - Note on the Treatment of Cold Abscess.

PMID- 29583923
TI  - On the Treatment of Gangrenous Bowel in Strangulated Hernia.

PMID- 29583924
TI  - On Some Points in the Technique of Laparotomy.

PMID- 29583925
TI  - Exhibition of Specimens.

PMID- 29583926
TI  - Exhibition of Patients.

PMID- 29583927
TI  - Exhibition of Patients.

PMID- 29583928
TI  - Exhibition of Patients.

PMID- 29583929
TI  - Notes of a Case of Carcinoma of Supra-Renal Capsules and Lungs; Kidneys Freely
      Movable.

PMID- 29583931
TI  - Exhibition of Pathological Specimens.

PMID- 29583930
TI  - Valedictory Address by the Retiring President.

PMID- 29583932
TI  - Exhibition of Patient.

PMID- 29583933
TI  - The Treatment of Flat-Foot.

PMID- 29583934
TI  - Exhibition of Instruments.

PMID- 29583936
TI  - On the Physiology of Education.

PMID- 29583935
TI  - Exhibition of Instrument.

PMID- 29583937
TI  - Exhibition of Specimens.

PMID- 29583939
TI  - Exhibition of Patients.

PMID- 29583938
TI  - Cyst of the Posterior Extremity of the Inferior Turbinated Body.

PMID- 29583940
TI  - Exhibition of Specimens.

PMID- 29583941
TI  - Exhibition of Patients.

PMID- 29583942
TI  - Exhibition of Specimen.

PMID- 29583943
TI  - Exhibition of Patients.

PMID- 29583944
TI  - On Lateral Curvature of the Spine.

PMID- 29583946
TI  - The Place of Systematic Lectures in the Teaching of Medicine and Surgery.

PMID- 29583945
TI  - Sequel to a Case of Ovariotomy: Pathological Report.

PMID- 29583947
TI  - Foetid Pleural Effusion.

PMID- 29583948
TI  - The Symptoms of Myxoedema and Exophthalmic Goitre Contrasted.

PMID- 29583950
TI  - Exhibition of Patient.

PMID- 29583949
TI  - Personal Impressions of Koch's Treatment at Berlin, with Early Notes of Cases
      Treated in the Royal Infirmary of Edinburgh.

PMID- 29583951
TI  - A Case of Hereditary Amaurosis.

PMID- 29583952
TI  - Exhibition of Specimen.

PMID- 29583953
TI  - Exhibition of Instrument.

PMID- 29583954
TI  - Exhibition of Patient.

PMID- 29583955
TI  - Exhibition of Patient.

PMID- 29583956
TI  - On the Function of the Tonsils.

PMID- 29583957
TI  - Wry-Neck: Its Varieties and Their Treatment.

PMID- 29583958
TI  - Cystoscopy: Notes from an Experience of Upwards of Fifty Cases.

PMID- 29583959
TI  - Exhibition of Specimen.

PMID- 29583961
TI  - On Relapse or Recrudescence in Scarlet Fever: Two Cases, with a Note on the
      Literature of the Subject.

PMID- 29583960
TI  - An Outbreak of Typhoid Fever Due to Milk Infection.

PMID- 29583962
TI  - Stricture of the OEsophagus-Gastrostomy.

PMID- 29583963
TI  - Exhibition of Patients.

PMID- 29583964
TI  - Recent Work in Abdominal Surgery.

PMID- 29583965
TI  - A Case of Spontaneous Pneumo-Thorax and Pneumo-Pericardium.

PMID- 29583966
TI  - The Relations of the Abdominal Viscera in the Infant.

PMID- 29583967
TI  - Dermatitis Herpetiformis: A Clinical Study.

PMID- 29583968
TI  - The Cardio-Pneumatic Movements.

PMID- 29583969
TI  - Exhibition of Patient.

PMID- 29583970
TI  - Exhibition of Patients.

PMID- 29583972
TI  - Exhibition of Specimens.

PMID- 29583971
TI  - Contribution to Venesection as a Remedy.

PMID- 29583973
TI  - The Pathology and Treatment of Furunculosis.

PMID- 29583974
TI  - On a Characteristic Organism of Cancer.

PMID- 29583975
TI  - Restorative Treatment of Varicose Veins.

PMID- 29583976
TI  - Exhibition of Specimens.

PMID- 29583977
TI  - Exhibition of Patients.

PMID- 29583978
TI  - Exhibition of Patients.

PMID- 29583979
TI  - Exhibition of Specimens.

PMID- 29583980
TI  - Some Remarks on the New Method of Treating Enlarged Prostate by Dr Bottini,
      Professor of Operative Surgery in the Royal University of Pavia.

PMID- 29583981
TI  - Exhibition of Specimens.

PMID- 29583982
TI  - Two Cases of Raynaud's Disease Occurring in James Murray's Royal Asylum, Perth.

PMID- 29583983
TI  - On Ruptures of the Pancreas, Their Relation to Pancreatic Cysts; with Some
      Remarks on Treatment.

PMID- 29583984
TI  - Exhibition of Photographs.

PMID- 29583986
TI  - Exhibition of Patients.

PMID- 29583985
TI  - Cardicentesis, with Successful Case (Case of Endocarditis and Pericarditis with
      Effusion; Accidental Tapping of Right Ventricle after Apparent Death; Recovery).

PMID- 29583988
TI  - Exhibition of Specimens.

PMID- 29583987
TI  - Carcinoma of the Splenic Flexure of the Colon.

PMID- 29583989
TI  - Exhibition of Patients.

PMID- 29583990
TI  - Exhibition of Instrument.

PMID- 29583991
TI  - Exhibition of Patients.

PMID- 29583992
TI  - Rupture of an Aortic Aneurism into the Superior Vena Cava.

PMID- 29583993
TI  - Notes on a Peculiar Case of Stricture of the OEsophagus.

PMID- 29583994
TI  - Exhibition of Patients.

PMID- 29583995
TI  - Statistics Concerning the Patients Admitted with Alcoholic Symptoms to the Royal
      Infirmary, Edinburgh, for the Five Years from 1st October 1889 to 20th September
      1894.

PMID- 29583996
TI  - On an Electrical Theory of the Physiology of Vision, Illustrated by Experiments.

PMID- 29583997
TI  - Exhibition of Specimens.

PMID- 29583999
TI  - Exhibition of Patients.

PMID- 29583998
TI  - Some Questions with Regard to the Diagnosis, Prognosis, and Treatment of
      Suppuration in Certain Osseous Cavities.

PMID- 29584000
TI  - On the Treatment of Ununited Fracture by Passive Congestion.

PMID- 29584001
TI  - Exhibition of Specimens.

PMID- 29584002
TI  - Chronic and Tubercular Pleurisy.

PMID- 29584003
TI  - Some Notes on the Surgery of the Bladder.

PMID- 29584004
TI  - Exhibition of Patients.

PMID- 29584005
TI  - Exhibition of Patients.

PMID- 29584006
TI  - The Probable Lesions in a Case of Incipient Caseous Pulmonary Phthisis of over
      Four Years' Duration, with No Physical Signs, but Abundant Bacilli in Sputum;
      with Some Remarks upon Their Diagnostic and Prognostic Value.

PMID- 29584007
TI  - On the Treatment of Fractures near a Joint by Rest, Aided by Massage and Passive
      Movement.

PMID- 29584008
TI  - Note on a Method of Trephining.

PMID- 29584009
TI  - On Resection and Suture of the Intestine, with Cases.

PMID- 29584011
TI  - Exhibition of Patients.

PMID- 29584010
TI  - On the Remedies Employed in Cardiac Affections and Their Indications.

PMID- 29584012
TI  - Exhibition of Patients.

PMID- 29584013
TI  - Exhibition of Specimens.

PMID- 29584014
TI  - The Palliative Treatment of Jaundice from Malignant Obstruction.

PMID- 29584015
TI  - Exhibition of Specimens.

PMID- 29584016
TI  - Notes on Skin Grafting from the Lower Animals.

PMID- 29584017
TI  - Exhibition of Patients.

PMID- 29584018
TI  - The Significance of the Venous Pulse.

PMID- 29584019
TI  - Note on the Action of Iodine.

PMID- 29584020
TI  - Clinical Remarks on a Case of Sporadic Cretinism.

PMID- 29584021
TI  - Some Notes on Surgical Economy in Hospitals.

PMID- 29584022
TI  - Microscopic Specimens from a Case of Syringomyelia.

PMID- 29584023
TI  - Note on Bier's New Method of Treating Strumous Diseases of the Extremities by
      Passive Congestion.

PMID- 29584024
TI  - Notes of a Case of Recurrent Fibrinous Rhinitis.

PMID- 29584025
TI  - Massage as an Adjuvant to Medical, Surgical, and Gynaecological Practice.

PMID- 29584027
TI  - Exhibition of Specimens.

PMID- 29584026
TI  - On Gastrostomy after the Method of Witzel.

PMID- 29584028
TI  - Exhibition of Specimens.

PMID- 29584029
TI  - Exhibition of Patients.

PMID- 29584030
TI  - A Case of Cancer of the Breasts, Spleen, and Other Organs, Which Presented Many
      Features of Clinical and Pathological Interest.

PMID- 29584031
TI  - Valedictory Address.

PMID- 29584033
TI  - Exhibition of Patients.

PMID- 29584032
TI  - Demonstration of the Microscopic Pathological Changes Found in the Brain and Its
      Membranes in Insanity.

PMID- 29584034
TI  - Notes on the Physics of an Aneurism, with Practical Illustrations.

PMID- 29584035
TI  - On Syphilitic Nodose Periarteritis.

PMID- 29584036
TI  - On Displacements of the Semilunar Cartilages of the Knee Joint, with Lantern
      Demonstration.

PMID- 29584037
TI  - Further Notes of a Case of Sporadic Cretinism, Treated by Thyroid Feeding.

PMID- 29584039
TI  - Exhibition of Patients.

PMID- 29584038
TI  - The Commoner Varieties of Lupus Vulgaris, and Their Treatment.

PMID- 29584040
TI  - Report upon the Microscopical Condition of the Different Organs, with Remarks
      upon the Pathology of the Case.

PMID- 29584041
TI  - On a Self-Inflicted Bullet Wound of the Head; Extensive Injury to Skull and
      Brain; Recovery.

PMID- 29584042
TI  - On Dr Heron Watson's Method of Excising the Wrist Joint.

PMID- 29584043
TI  - Intra-Cranial Surgery.

PMID- 29584045
TI  - Exhibition of Patients.

PMID- 29584044
TI  - Exhibition of Patients.

PMID- 29584046
TI  - Exhibition of Specimens.

PMID- 29584047
TI  - The Action of Acids and Alkalies, and of Some Other Drugs, on the Secretions of
      the Body.

PMID- 29584048
TI  - Practical Demonstration on the Therapeutic Methods Employed in Static
      Electricity, with Exhibition of Apparatus.

PMID- 29584049
TI  - Note on Certain Changes in the Circulation Produced by Pyrexia.

PMID- 29584051
TI  - On a Case of Renal Tumour.

PMID- 29584050
TI  - Exhibition of Patients.

PMID- 29584052
TI  - The New Hospital to Be Erected by the City of Edinburgh at Colinton Mains for the
      Treatment of Infectious Diseases.

PMID- 29584054
TI  - Exhibition of Patients.

PMID- 29584053
TI  - On Basal Meningitis, with a Chart.

PMID- 29584055
TI  - Toxicology in the Punjab: The Record of a Year's Experience as Chemical Examiner
      for the Punjab.

PMID- 29584057
TI  - Exhibition of Specimens.

PMID- 29584056
TI  - Agraphia: And the Question of the Existence of a Special Graphic Centre.

PMID- 29584058
TI  - Exhibition of Specimens.

PMID- 29584059
TI  - Exhibition of Patients.

PMID- 29584060
TI  - Exhibition of Patients.

PMID- 29584061
TI  - A Lantern Demonstration of a Descending Tract in the Posterior Column of the
      Spinal Cord in the Lumbo-Sacral Region, and Also of Sections of the Cord from a
      Case of Amyotrophic Lateral Sclerosis.

PMID- 29584062
TI  - On Congenital Spasm (Congenital Hypertrophy and Stenosis of the Pylorus).

PMID- 29584063
TI  - On the Endogenous or Intrinsic Fibres in the Lumbo-Sacral Region of the Cord.

PMID- 29584064
TI  - On Apparent Reduplication of the Second Sound in Mitral Stenosis.

PMID- 29584066
TI  - Exhibition of Specimens.

PMID- 29584065
TI  - Exhibition of Patients.

PMID- 29584067
TI  - Exhibition of Patients.

PMID- 29584068
TI  - Exhibition of Patients.

PMID- 29584069
TI  - A Lantern Demonstration of Slides Illustrative of the Clinical and Microscopic
      Appearances of the Muscles, Spinal Cord and Peripheral Nerves in Cases of Pseudo
      Hypertrophic Paralysis and Myopathic Muscular Atrophy.

PMID- 29584070
TI  - Exhibition of Instrument.

PMID- 29584071
TI  - Exhibition of Specimens.

PMID- 29584073
TI  - Exhibition of Specimens.

PMID- 29584072
TI  - Unilateral Hydrocephalus-Epileptiform Convulsions and Hemianopsia-Drainage of
      Lateral Ventricle.

PMID- 29584074
TI  - The Perigraph-An Instrument for Delineating the Shape of the Thorax, and for
      Clinical Mensuration Generally.

PMID- 29584075
TI  - Exhibition of Specimens.

PMID- 29584076
TI  - Exhibition of Specimens.

PMID- 29584077
TI  - The Treatment of Crime.

PMID- 29584078
TI  - A Case in Which a Fragment of Steel Was Removed from the Vitreous Humour.

PMID- 29584079
TI  - On Trade-Like Movements Following Head Injuries.

PMID- 29584080
TI  - On the Use of Picric Acid as a Primary Dressing for Burns.

PMID- 29584081
TI  - Resilient Stricture of the Urethra and Its Treatment.

PMID- 29584083
TI  - Exhibitions of Specimens.

PMID- 29584082
TI  - The Importance of Asepsis in Genito-Urinary Surgery.

PMID- 29584084
TI  - Notes on Cases of Gall-Stone.

PMID- 29584085
TI  - Dual Brain Action and Its Relation to Certain Epileptic States.

PMID- 29584086
TI  - Note on the Physics of the Cranial Cavity.

PMID- 29584087
TI  - Exhibition of Instruments.

PMID- 29584089
TI  - Exhibition of Specimens.

PMID- 29584088
TI  - An Inquiry into the Physiology of the Action of Thermal Saline Baths and
      Resistance Exercises in the Treatment of Chronic Heart Disease (the Nauheim and
      Schott System).

PMID- 29584090
TI  - Exhibition of Specimen.

PMID- 29584092
TI  - Exhibition of Photographs.

PMID- 29584091
TI  - On the Action of the Liver on Fats; an Abstract.

PMID- 29584093
TI  - Case of Deep-Seated Tropical Abscess of the Liver, Treated by Transthoracic
      Hepatotomy; Recovery.

PMID- 29584094
TI  - A Remarkable Case of Calcareous Degeneration of the Heart and Arteries.

PMID- 29584095
TI  - Exhibition of Specimens and Gelatine Cast.

PMID- 29584096
TI  - Valedictory Address.

PMID- 29584097
TI  - On a Case of Diabetic Neuritis, with a Description of the Post-Mortem Examination
      of the Nerves and Muscles.

PMID- 29584099
TI  - On the Treatment of Inoperable Cases of Carcinoma of the Mamma: Suggestions for a
      New Method of Treatment, with Illustrative Cases.

PMID- 29584098
TI  - Short Notes on Two Cases of Opium Poisoning.

PMID- 29584100
TI  - Exhibition of Patients.

PMID- 29584102
TI  - A Few More Words on Strophanthus.

PMID- 29584101
TI  - On Contraction of the Arteries of a Limb the Probable Cause of Muscle Atrophy in
      Tubercular Joint Disease.

PMID- 29584103
TI  - Exhibition of Patient.

PMID- 29584105
TI  - Exhibition of Patient.

PMID- 29584104
TI  - On the Weather, Influenza, and Disease from the Infirmary Records.

PMID- 29584106
TI  - Exhibition of Patients.

PMID- 29584107
TI  - A Lantern Demonstration Illustrating the Pathology of the Appendix Vermiformis.

PMID- 29584108
TI  - Exhibition of Specimens.

PMID- 29584110
TI  - Exhibition of Specimens.

PMID- 29584109
TI  - Remarks on the Results of Surgical Measures in a Series of Cerebral Cases.

PMID- 29584111
TI  - Exhibition of Patients.

PMID- 29584112
TI  - Exhibition of Patients.

PMID- 29584113
TI  - On Separate Acromion Process Simulating Fracture.

PMID- 29584114
TI  - Enormous Primary Scaroma of the Liver, in Which a Large Blood-Cyst, Simulating a
      Hepatic Abscess, Was Developed.

PMID- 29584115
TI  - Exhibition of Patients.

PMID- 29584116
TI  - The Blood in Diabetes Mellitus.

PMID- 29584117
TI  - Exhibition of Patient.

PMID- 29584118
TI  - General Secondary Carcinoma of the Bones: Osteomalacia Carcinomatosa.

PMID- 29584119
TI  - Oxaluria and the Excretion of Oxalic Acid in Urine; an Abstract.

PMID- 29584120
TI  - Exhibition of Specimens, Etc.

PMID- 29584121
TI  - Exhibition of Patients.

PMID- 29584122
TI  - A Series of Photographs Taken by the Rontgen Process, Exhibited by Means of the
      Lantern.

PMID- 29584123
TI  - Exhibition of Instruments.

PMID- 29584124
TI  - Ophthalmia Neonatorum, Especially in Reference to Its Prevention.

PMID- 29584125
TI  - Exhibition of Patient.

PMID- 29584126
TI  - The Role of the Carbohydrates in Dietetics.

PMID- 29584127
TI  - Exhibition of Instrument.

PMID- 29584129
TI  - Exhibition of Specimens.

PMID- 29584128
TI  - Valedictory Address.

PMID- 29584130
TI  - The AEtiology and Treatment of Glandular Enlargements in the Neck.

PMID- 29584132
TI  - Exhibition of Specimens.

PMID- 29584131
TI  - Rheumatic Myosotis-Subacute and Chronic.

PMID- 29584133
TI  - Exhibition of Photographs, &c.

PMID- 29584134
TI  - Exhibition of Specimens.

PMID- 29584135
TI  - Exhibition of Instrument.

PMID- 29584137
TI  - Exhibition of Specimens.

PMID- 29584136
TI  - Acute Pneumonia of Childhood.

PMID- 29584138
TI  - The Serum Diagnosis of Enteric Fever.

PMID- 29584139
TI  - Exhibition of Patients.

PMID- 29584140
TI  - Exhibition of Patients.

PMID- 29584142
TI  - Exhibition of Patients.

PMID- 29584141
TI  - Personal Experiences in the Treatment of Enlarged Prostate.

PMID- 29584143
TI  - Exhibition of Specimens.

PMID- 29584144
TI  - On the Diagnosis and Prognosis of Certain Forms of Imbecility in Infancy.

PMID- 29584145
TI  - Localisation of Foreign Bodies by X Rays.

PMID- 29584147
TI  - Exhibition of Patients.

PMID- 29584146
TI  - Exhibition of Specimens.

PMID- 29584148
TI  - Exhibition of Patients.

PMID- 29584149
TI  - Exhibition of Specimens.

PMID- 29584150
TI  - Exhibition of Patients.

PMID- 29584151
TI  - Exhibition of Patients.

PMID- 29584152
TI  - Liver Cirrhosis and Its Varieties.

PMID- 29584153
TI  - A Fit of Gout (Paroxysmus Podagrae): A Study in Pathology.

PMID- 29584154
TI  - Eczema Palmare and Plantare.

PMID- 29584156
TI  - Exhibition of Specimens.

PMID- 29584155
TI  - Drainage through the Fourth Ventricle in a Case of Acquired Hydrocephalus Due to
      Chronic Non-Tubercular Basal Meningitis.

PMID- 29584157
TI  - The Etiology of Gout: Observations on the Pathological Relationships of Uric
      Acid.

PMID- 29584158
TI  - On a Case of Cerebral Abscess, Illustrating Certain Forms of Aphasia.

PMID- 29584159
TI  - Exhibition of Specimens.

PMID- 29584160
TI  - A Case of Hereditary Syphilitic Osteitis.

PMID- 29584161
TI  - Exhibition of Patients.

PMID- 29584162
TI  - Exhibition of Patients.

PMID- 29584163
TI  - Exhibition of Pathological Specimens.

PMID- 29584164
TI  - On Movable Kidney.

PMID- 29584165
TI  - Exhibition of Specimens.

PMID- 29584166
TI  - Exhibition of Instruments.

PMID- 29584167
TI  - Exhibition of Patients.

PMID- 29584169
TI  - Exhibition of Instruments.

PMID- 29584168
TI  - A Case of Cerebellar Tumour, Considered with Reference to Its Localisation.

PMID- 29584170
TI  - Some Observations on the Development of the Testicle.

PMID- 29584171
TI  - Exhibition of Patients.

PMID- 29584172
TI  - Peritonitis as a Cause of Increased Peristalsis in the Rectum and in Other Parts
      of the Intestine.

PMID- 29584173
TI  - Regurgitation at the Pulmonary Artery.

PMID- 29584175
TI  - Exhibition of Specimens.

PMID- 29584174
TI  - An Outbreak of Typhus Fever.

PMID- 29584176
TI  - Exhibition of Specimens.

PMID- 29584177
TI  - Exhibition of Patients.

PMID- 29584178
TI  - Exhibition of Specimens.

PMID- 29584179
TI  - Exhibition of Specimens.

PMID- 29584180
TI  - Acute Yellow Atrophy of the Liver.

PMID- 29584181
TI  - Exhibition of Patients.

PMID- 29584183
TI  - Exhibition of Patients.

PMID- 29584182
TI  - The Localisation and Symptoms of Disease of the Cerebellum, Considered in
      Relation to Its Anatomical Connections.

PMID- 29584184
TI  - Exhibition of Patients.

PMID- 29584185
TI  - Tubercular Neuritis.

PMID- 29584187
TI  - Exhibition of Pathological Specimens.

PMID- 29584186
TI  - Exhibition of Specimens.

PMID- 29584188
TI  - Exhibition of Patients.

PMID- 29584189
TI  - Sulphonal Poisoning.

PMID- 29584190
TI  - The Treatment of Ozaena, with Special Reference to Cupric Electrolysis.

PMID- 29584191
TI  - Note on a Case of Ruptured Femoral Aneurism for Which the Common Femoral Artery
      Was Tied.

PMID- 29584192
TI  - The Activity of the Saliva in Diseased Conditions of the Body.

PMID- 29584194
TI  - Exhibition of Patients.

PMID- 29584193
TI  - Valedictory Address.

PMID- 29584195
TI  - Cross Infection, so Called, in Fever Hospitals.

PMID- 29584197
TI  - Exhibition of Instrument.

PMID- 29584196
TI  - A Demonstration of the Advantage of Having Gauze Dressings Rolled in the Form of
      Balls, Which Pull out from the inside.

PMID- 29584199
TI  - Some Observations upon the General Blood Pressure in Sleeplessness and Sleep.

PMID- 29584198
TI  - Exhibition of Specimens.

PMID- 29584200
TI  - Permanent Dislocation of the Patella.

PMID- 29584202
TI  - Exhibition of Patients.

PMID- 29584201
TI  - The Origin and Development of the Umbilical Cord and Its Relation to the Amnion.

PMID- 29584203
TI  - Exhibition of Instruments.

PMID- 29584205
TI  - Exhibition of Specimens.

PMID- 29584204
TI  - On Heredity in Disease.

PMID- 29584206
TI  - Exhibition of Pathological Specimen.

PMID- 29584207
TI  - Exhibition of Patients.

PMID- 29584208
TI  - A Case of Murder and Suicide.

PMID- 29584210
TI  - Exhibition of Specimens.

PMID- 29584209
TI  - On the Increase of Diseases of the Nervous System and of Insanity.

PMID- 29584211
TI  - Exhibition of Patients.

PMID- 29584212
TI  - Exhibition of Pathological Specimens.

PMID- 29584213
TI  - Exhibition of Patients.

PMID- 29584214
TI  - Exhibition of Patients.

PMID- 29584215
TI  - Clinical Note on Residual Urine in Cases of Enlarged Prostate.

PMID- 29584216
TI  - Exhibition of Pathological Specimens.

PMID- 29584217
TI  - Exhibition of Patients.

PMID- 29584218
TI  - Paralysis of Vertical with Conservation of Lateral Conjugate Movements of Both
      Eyeballs.

PMID- 29584219
TI  - Clinical Experience with Salol in Treatment of Small-Pox.

PMID- 29584220
TI  - On the Importance of Examining the Blood in Doubtful Cases of Disease.

PMID- 29584221
TI  - On the Radical Cure of Hernia, with the Statistics of Seven Years' Experience in
      the Royal Infirmary.

PMID- 29584222
TI  - Case of Meningeal Cerebral Haemorrhage and Meningitis in a Case of Haemophilia.

PMID- 29584224
TI  - Exhibition of Patient.

PMID- 29584223
TI  - On the Operative Treatment of Popliteal Aneurism.

PMID- 29584225
TI  - On Abdominal Section.

PMID- 29584227
TI  - A Demonstration of the New Modes of Treating Skin Diseases Introduced by Dr Unna,
      of Hamburg.

PMID- 29584226
TI  - Case of Intra-Tracheal Tumour.

PMID- 29584228
TI  - Illustrations of Uncommon Morbid Conditions of the Ear, Nose, and Larynx.

PMID- 29584229
TI  - On Compression of the Innominate Artery, with Notes of a Case.

PMID- 29584231
TI  - Exhibition of Patient.

PMID- 29584230
TI  - A Case of Strychnia Poisoning, with an Analysis of Steiner's Vermin-Killer.

PMID- 29584232
TI  - Exhibition of Pathological Specimens, Etc.

PMID- 29584233
TI  - Exhibition of Patients.

PMID- 29584234
TI  - Note on Dr Bruce's Demonstration of Weigert's Method of Embedding and Staining
      Nerve Centres.

PMID- 29584235
TI  - Notes on the Position of the Fluid in Cases of Pleuritic Effusion.

PMID- 29584236
TI  - Valedictory Address.

PMID- 29584237
TI  - Exhibition of Pathological Specimens.

PMID- 29584239
TI  - Exhibition of Pathological Specimens.

PMID- 29584238
TI  - The Medical Arrangements of an English Army Corps in War, with Suggestions as to
      Volunteer Help.

PMID- 29584240
TI  - Exhibition of Drug-Vehicle.

PMID- 29584241
TI  - Exhibition of Instrument.

PMID- 29584242
TI  - Exhibition of Patients.

PMID- 29584243
TI  - Exhibition of Patient.

PMID- 29584244
TI  - An Improved Method for the Easy Detection of the Bacilli of Tubercle.

PMID- 29584245
TI  - Exhibition of Pathological Specimens and Demonstrations.

PMID- 29584246
TI  - Exhibition of Pathological Specimens.

PMID- 29584247
TI  - Exhibition of Patients.

PMID- 29584248
TI  - Exhibition of Inventions.

PMID- 29584249
TI  - Exhibition of Pathological Preparations.

PMID- 29584250
TI  - On Re-Infusion of Blood in Primary and Other Amputations.

PMID- 29584251
TI  - Exhibition of Pathological Specimens.

PMID- 29584253
TI  - Exhibition of Patients.

PMID- 29584252
TI  - On the Cold Nitric Acid Test for Albumen in the Urine as an Aid to the Detection
      of the Bile Salts.

PMID- 29584255
TI  - A Nasal Insufflator.

PMID- 29584254
TI  - Diphtheria.

PMID- 29584256
TI  - The Bronchial Catarrh of Children.

PMID- 29584257
TI  - Exhibition of Patient.

PMID- 29584258
TI  - Exhibition of Pathological Specimens.

PMID- 29584259
TI  - Cases of Ovariotomy.

PMID- 29584260
TI  - Case of a Full-Grown Foetus, Exhibiting the Rare Malformation of a Cyclops. With
      an Anatomical Description of the Parts.

PMID- 29584261
TI  - Exhibition of Patient.

PMID- 29584262
TI  - The Relation of Goitre to Menstruation and Pregnancy, and the Influence of the
      Sympathetic System on Its Production.

PMID- 29584264
TI  - Exhibition of Specimens and Photographs.

PMID- 29584263
TI  - Exhibition of Specimens.

PMID- 29584266
TI  - Exhibition of Patients.

PMID- 29584265
TI  - On the Remedies Used by the Caffres to Prevent Blood Poisoning from Anthrax.

PMID- 29584267
TI  - The Dyspnoea of Asthma and Bronchitis: Its Causation and the Influence of
      Nitrites upon It.

PMID- 29584268
TI  - Second Report of Said Committee Presented.

PMID- 29584270
TI  - Exhibition of Specimens.

PMID- 29584269
TI  - The Adenoid Tissue at the Base of the Tongue as a Factor of Throat Symptoms.

PMID- 29584271
TI  - Melanotic Sarcoma, Primarily of the Skin, Secondarily of the Brain and Other
      Organs.

PMID- 29584273
TI  - Exhibition of Patients.

PMID- 29584272
TI  - Exhibition of Patients.

PMID- 29584274
TI  - Exhibition of Pathological Specimens.

PMID- 29584275
TI  - Removal of the Uterine Appendages for Disease, with Twenty-Three Cases.

PMID- 29584276
TI  - Exhibition of Pathological Specimens.

PMID- 29584278
TI  - Exhibition of Pathological Specimens.

PMID- 29584277
TI  - A Case of Cerebral Tumour. With Pathological Report.

PMID- 29584279
TI  - Exhibition of Patient.

PMID- 29584280
TI  - Exhibition of Pathological Specimens.

PMID- 29584281
TI  - On Empyema.

PMID- 29584282
TI  - Interim Report of Committee Appointed by the Medico-Chirurgical Society of
      Edinburgh to Investigate the Nature of the Contagium of Scarlet Fever.

PMID- 29584283
TI  - On a Case of Poisoning by Corrosive Sublimate.

PMID- 29584284
TI  - Exhibition of Pathological Specimens.

PMID- 29584285
TI  - Exhibition of Specimens.

PMID- 29584286
TI  - On the Pathology of Blood Destruction within the Liver.

PMID- 29584288
TI  - Note on Preliminary Tracheotomy as an Aid to Certain Operations.

PMID- 29584287
TI  - Exhibition of Patients.

PMID- 29584289
TI  - Exhibition of Patients.

PMID- 29584291
TI  - Exhibition of Patients.

PMID- 29584290
TI  - Notes on Unusual Microscopic Elements in Food Materials from a Case of Irritant
      Poisoning.

PMID- 29584292
TI  - Exhibition of Instruments.

PMID- 29584293
TI  - Note on the Condition of Stiff Great Toe in Adolescence.

PMID- 29584294
TI  - A Case of Cerebral Tumour of Unusual Clinical and Pathological Interest.

PMID- 29584295
TI  - Exhibition of Patients.

PMID- 29584296
TI  - On Poisonous Products in Food-Stuffs.

PMID- 29584297
TI  - Exhibition of Instrument, Etc.

PMID- 29584298
TI  - Exhibition of Instrument.

PMID- 29584299
TI  - The Diagnosis and Treatment of Cerebral Abscess Due to Ear Disease: Part I. Part
      II.

PMID- 29584300
TI  - Pathological Specimens.

PMID- 29584301
TI  - The Shoulder-Joint in Relation to Certain Dislocations and Fractures.

PMID- 29584302
TI  - An Address on Internal Derangements of the Knee-Joint and Their Treatment by
      Operation.

PMID- 29584303
TI  - Observations on a Case of Mycosis Fungoides.

PMID- 29584304
TI  - Exhibition of Patient.

PMID- 29584305
TI  - What Constitutes Rodent Ulcer?

PMID- 29584306
TI  - The Treatment of Anaemia and Chlorosis by the Chief Iron Preparations Commonly in
      Use.

PMID- 29584307
TI  - On the Surgical Treatment of Gall-Stones.

PMID- 29584308
TI  - Exhibition of Patient.

PMID- 29584309
TI  - A New Instrument for the Treatment of Difficult Strictures of the Urethra.

PMID- 29584310
TI  - Pachydermia of the Larynx.

PMID- 29584312
TI  - Discussion on Suggestions for a Society Hall.

PMID- 29584311
TI  - Some Practical Results from the Chemical Examination of the Contents of the
      Healthy Stomach.

PMID- 29584313
TI  - The Treatment of Myxoedema.

PMID- 29584314
TI  - Exhibition of Patients.

PMID- 29584315
TI  - Some Practical Results of the Investigation of Cholera in Germany.

PMID- 29584316
TI  - The Pathology and Morbid Anatomy of Myxoedema.

PMID- 29584317
TI  - Excision or Arthrectomy of the Knee-Joint.

PMID- 29584318
TI  - Some Mistakes in the Technique of Abdominal Surgery.

PMID- 29584319
TI  - A Case of Acquired Umbilical Faecal Fistula.

PMID- 29584321
TI  - Exhibition of Patients.

PMID- 29584320
TI  - Exhibition of Instruments.

PMID- 29584323
TI  - Exhibition of Patient.

PMID- 29584322
TI  - Exhibition of Patients.

PMID- 29584324
TI  - Exhibition of Specimens.

PMID- 29584326
TI  - Strangulation and Hanging.

PMID- 29584325
TI  - Notes of a Case of Ruptured Kidney, with Recovery after Lumbar Incision and
      Drainage.

PMID- 29584327
TI  - The Clinical Features of Myxoedema.

PMID- 29584328
TI  - The Operation for Inflammation of the Appendix Vermiformis.

PMID- 29584329
TI  - Note on the Quenching of Thirst after Abdominal Operations.

PMID- 29584330
TI  - Case of Cancrum Oris.

PMID- 29584331
TI  - On Amputation in Cases of Gangrene of the Lower Extremity.

PMID- 29584332
TI  - Exhibition of Patients.

PMID- 29584333
TI  - Exhibition of Instrument.

PMID- 29584334
TI  - Exhibition of Specimens.

PMID- 29584335
TI  - Exhibition of Specimens.

PMID- 29584336
TI  - Pathological Report.

PMID- 29584337
TI  - A Case of Cancrum Oris, with a Short Critique on the Disease.

PMID- 29584338
TI  - Notes on a Case of Gastrostomy, and on Hypodermic Alimentation.

PMID- 29584339
TI  - Exhibition of Patients.

PMID- 29584340
TI  - Observations upon Disease of the Appendix Vermiformis and Its Results.

PMID- 29584341
TI  - Cystoscopy in Relation to Tumours of the Bladder.

PMID- 29584342
TI  - A Thousand Cases of Pulmonary Tuberculosis, with Etiological and Therapeutic
      Considerations.

PMID- 29584343
TI  - Exhibition of Specimen.

PMID- 29584344
TI  - Cysts of the Tonsils, Nose, Larynx, and Ear.

PMID- 29584345
TI  - Notes on Toxic Effects of Exalgin.

PMID- 29584346
TI  - Exhibition of Specimen.

PMID- 29584347
TI  - Some Questions with Regard to Tuberculosis of the Upper Air Passages.

PMID- 29584348
TI  - The Antiseptic Treatment of Pernicious Anaemia.

PMID- 29584349
TI  - Exhibition of Preparation.

PMID- 29584350
TI  - Observations on the Action of Antimony in Diseases of the Skin.

PMID- 29584352
TI  - Exhibition of Patient.

PMID- 29584351
TI  - Note on Two Cases of Cerebral Haemorrhage.

PMID- 29584353
TI  - On Ectopic Gestation.

PMID- 29584354
TI  - Exhibition of Patient.

PMID- 29584355
TI  - Some Deductions from a Study of the Development of the Heart.

PMID- 29584356
TI  - Two Hundred and Fifty-Eight Cases of Suffocation of Infants.

PMID- 29584357
TI  - Exhibition of Patients.

PMID- 29584358
TI  - Exhibition of Specimens.

PMID- 29584360
TI  - An Extreme Case of Hystero-Catalepsy, Trances Lasting 58, 30, 24, and 12 Hours;
      Insanity; Recovery.

PMID- 29584359
TI  - Notes on a Case of Paroxysmal Methaemoglobinuria.

PMID- 29584361
TI  - Empyema, Basal Lung Disease, and Bronchiectatic Cavities.

PMID- 29584362
TI  - Exhibition of Patients.

PMID- 29584363
TI  - On Infantile Respiratory Spasm (Congenital Laryngeal Stridor).

PMID- 29584364
TI  - The Dietetic Treatment of Obesity.

PMID- 29584366
TI  - Exhibition of Patients.

PMID- 29584365
TI  - Contributions to the Surgical Anatomy of the Breast and Axillary Lymphatic
      Glands, Illustrated by Lime-Light and Microscopical Demonstrations.

PMID- 29584367
TI  - Remarks on the Surgical Treatment of General Paralysis of the Insane.

PMID- 29584368
TI  - Valedictory Address.

PMID- 29584369
TI  - The History, Causation, and Prevention of the Enteric Fever of India.

PMID- 29584370
TI  - Electro-Diagnosis by Means of the Urine.

PMID- 29584371
TI  - On the Restoration of the Apparently Drowned.

PMID- 29584372
TI  - On the Mechanism of Cerebral Concussion.

PMID- 29584374
TI  - Exhibition of Patients.

PMID- 29584373
TI  - Transfusion of Human Blood in the Treatment of Pernicious Anaemia.

PMID- 29584375
TI  - On Cervical Ribs, with Example in Living Subject.

PMID- 29584376
TI  - The Spinal Column in the Infant.

PMID- 29584377
TI  - Gastric Haemorrhage and Its Surgical Treatment.

PMID- 29584378
TI  - On Bier's Treatment of Acute Inflammation by Passive Congestion.

PMID- 29584379
TI  - Two Rare Cases of Sudden Death in Medico-Legal Practice.

PMID- 29584381
TI  - Exhibition of Patients.

PMID- 29584380
TI  - Case of Acute Ascending Paralysis Due to Influenza.

PMID- 29584382
TI  - Exhibition of Specimens.

PMID- 29584384
TI  - A Case of Left Facial Paralysis with Strabismus, Considered Clinically, and with
      Reference to Localization of the Lesion.

PMID- 29584383
TI  - Note on Lameness after Hip-Joint Disease.

PMID- 29584385
TI  - On the Specific Gravity of the Different Parts of the Human Body.

PMID- 29584386
TI  - Account of the Epidemic Erysipelas, Which Appeared in Montrose and the
      Neighbourhood in 1822.

PMID- 29584387
TI  - Affections of the Heart, the Prognosis in Certain.

PMID- 29584388
TI  - Leptothrix Infections. A Case of Pyaemia with Meningitis, and Notes of Two
      Similar Cases.

PMID- 29584389
TI  - Chronic Intestinal Obstruction Caused by Annular Stricture (Malign) of the Large
      Intestine.

PMID- 29584390
TI  - Exhibition of Patients.

PMID- 29584391
TI  - [Prevention and detection of obstetric violence: A need in the Spanish delivery
      rooms?].
AB  - Introduction: The obstetric violence (OV) is the type of violence perpetrated
      against the pregnant woman through acts such as lack of respect to her autonomy
      and her freedom to decide.  The increasing medicalization of the labour process,
      seems to be associated to this type of violence. Objective: Our objective is to
      provide health professionals with the necessary knowledge to be able to inform
      their patients about their rights and recognize those situations that can imply
      violence during the care process. Material and methods: The literature search was
      conducted in the following databases: PubMed, Cochrane Database of Systematic
      Reviews, EMBASE, Joanna Briggs Institute, UpToDate and CUIDEN.  The search was
      limited to articles published during the last five years.  The next medical
      subject heading were used both in English and Spanish: "humanizing delivery",
      "obstetrics", "medicalization" and "violence". Results: The performance of
      harmful practices and the unjustified medicalization of the labour process
      represent a potential damage to pregnant women by action, violating their rights
      as a result.  To prevent and eradicate this, new lines of less interventionist
      work are being proposed. Conclusion: As health professionals we should promote
      the humanization of labour and informs women about the existent legislation,
      protocols and guidelines that offer adequate information based on the latest
      evidence and promote their advance role as patients.  The health institutions are
      responsible for initiating this change, by implementing protocols to guide the
      practice of the health professionals involved in the care of women during labour.
      These protocols should be based on the WHO recommendations.

PMID- 29584392
TI  - [Fundamental aspects in the choice of renal replacement therapy].
AB  - Chronic kidney disease (CKD) is a disease with a high prevalence in our
      environment, and those suffering the disease should be as clear as possible that
      renal replacement therapy (RRT) may better suit your lifestyle.  It is important
      that the patient has enough information about the techniques that can be accessed
      in a clear manner, so as to evaluate the different possibilities, advantages and
      disadvantages.  The timing on this election is crucial and stressful for the
      patient's life, not only by the effects of the disease itself, but also by the
      assimilation of a new lifestyle that should keep the rest of it.This work was
      done thinking about the need for patients and health professionals in acquiring a
      holistic and comprehensive understanding of all the features that can have both
      peritoneal dialysis (PD) and hemodialysis (HD); form own patient factors (diet,
      family environment, etc.) related to nurses (care, information provided, etc.)
      without forgetting the conditions outside the patient and the nurse as they can
      be structural and economic aspects.

PMID- 29584394
TI  - ?Que entendemos hoy por formarse?

PMID- 29584393
TI  - [Elderly caregivers of elderly people].
AB  - The ageing of the population is a reality in our society nowadays.  The aging
      process changes increase the probability that health problems occur.  This fact
      involves that the needs of care demanded by the population increase too.  The
      care for the elderly generally are provided in home environments, where often,
      the primary caregiver is another old person.  In this sense, must be taken into
      account that this stage of life, the old age, although there has been important
      improvements in the quality of life and in the resolution of health problems,
      presents certain limitations refers to physical and mental declines that affect
      to the functional capacity of elderly caregivers.  For this reason, it is
      necessary to carry out a comprehensive geriatric assessment to identify
      unresolved needs and establish care strategies required to attend their demands
      for care.

PMID- 29584395
TI  - pi-Extended Benzoporphyrin-Based Metal-Organic Framework for Inhibition of Tumor
      Metastasis.
AB  - We report on the benzoporphyrin-based metal-organic framework (TBP-MOF), with 10
      connected Zr6 cluster and much improved photophysical properties over the
      traditional porphyrin-based MOFs. It was found that TBP-MOF exhibited red-shifted
      absorption bands and strong near-infrared luminescence for bioimaging, whereas
      the pi-extended benzoporphyrin-based linkers of TBP-MOF facilitated 1O2
      generation to enhance O2-dependent photodynamic therapy (PDT). It was
      demonstrated that poly(ethylene glycol)-modified nanoscale TBP-MOF (TBP-nMOF) can
      be used as an effective PDT agent under hypoxic tumor microenvironment. We also
      elucidated that the low O2-dependent PDT of TBP-nMOF in combination with alphaPD
      1 checkpoint blockade therapy can not only suppress the growth of primary tumor,
      but also stimulate an antitumor immune response for inhibiting metastatic tumor
      growth. We believe this TBP-nMOF has great potential to serve as an efficient
      photosensitizer for PDT and cancer immunotherapy.

PMID- 29584396
TI  - Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable
      Hydrogel for Tissue Engineering.
AB  - Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical
      fields, because of its slow biodegradability, good biocompatibility, and low
      immunogenicity. Although SF-based hydrogels have been studied intensively as a
      potential matrix for tissue engineering, weak gelation performance and low
      mechanical strength are major limitations that hamper their widespread
      applicability. Therefore, searching for new strategies to improve the SF gelation
      property is highly desirable in tissue engineering research. Herein, we report a
      facile approach to induce rapid gelation of SF by a small peptide gelator (e.g.,
      NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel
      of SF was obtained in a short time period at physiological pH, and the minimum
      gelation concentration of SF can reach as low as 0.1%. In this process of
      gelation, NapFF not only can behave itself as a gelator for supramolecular self
      assembly, but also can trigger the conformational transition of the SF molecule
      from random coil to beta-sheet structure via hydrophobic and hydrogen-bonding
      interactions. More importantly, for the generation of a scaffold with favorable
      cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp
      (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity
      for cell adhesion and growth. Following encapsulating the vascular endothelial
      growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served
      as an effective matrix to trigger the generation of new blood capillaries in
      vivo.

PMID- 29584397
TI  - Toward Highly Luminescent and Stabilized Silica-Coated Perovskite Quantum Dots
      through Simply Mixing and Stirring under Room Temperature in Air.
AB  - Methylammonium (MA) lead halide (MAPbX3, X = Cl, Br, I) perovskite quantum dots
      (PQDs) are very sensitive to environment (moisture, oxygen, and temperature),
      suffering from poor stability. To improve the stability, we synthesized silica
      coated PQDs (SPQDs) by an improved ligand-assisted reprecipitation method through
      simply mixing and stirring under room temperature in air without adding water and
      catalyst, the whole process took only a few seconds. The photoluminescence (PL)
      spectra of the SPQDs can be tuned continuously from 460 to 662 nm via adjusting
      the composition proportion of precursors. The highest PL quantum yields (PLQYs)
      of blue-, green-, and red-emissive SPQDs are 56, 95, and 70%, respectively. The
      SPQDs show remarkably improved environmental and thermal stability compared to
      the naked PQDs because of effective barrier created by the coated silica between
      the core materials and the ambience. Furthermore, it is found that different
      light-emitting SPQDs can maintain their original PL properties after mixing of
      them and anion-exchange reactions have not happened. These attributes were then
      used to mix green- and yellow-emissive SPQDs with polystyrene (PS) to form color
      converting layers for the fabrication of white light-emitting devices (WLEDs).
      The WLEDs exhibit excellent white light characteristics with CIE 1931 color
      coordinates of (0.31, 0.34) and color rendering index (CRI) of 85, demonstrating
      promising applications of SPQDs in lighting and displays.

PMID- 29584398
TI  - A Biomimetic Conductive Tendril for Ultrastretchable and Integratable
      Electronics, Muscles, and Sensors.
AB  - Adaptive tendril coiling of climbing plants has long inspired the artificial soft
      microsystem for actuation and morphing. The current bionic research efforts on
      tendril coiling focus on either the preparation of materials with the coiling
      geometry or the design of self-shaping materials. However, the realization of two
      key functional features of the tendril, the spring-like buffering connection and
      the axial contraction, remains elusive. Herein, we devise a conductive tendril by
      fusing conductive yarns into tendril configuration, bypassing the prevailing
      conductivity constraints and mechanical limitations. The conductive tendril not
      only inherits an electrophysiology buffering mechanics with exceptional
      conductance retention ability against extreme stretching but also exhibits
      excellent contractive actuation performance. The integrative design of the
      ultraelastic conductive tendril shows a combination of compliant mobility,
      actuation, and sensory capabilities. Such smart biomimetic material holds great
      prospects in the fields of ultrastretchable electronics, artificial muscles, and
      wearable bioelectronic therapeutics.

PMID- 29584400
TI  - Thieno[3,2- b]pyrrole-benzothiadiazole Banana-Shaped Small Molecules for Organic
      Field-Effect Transistors.
AB  - We report two banana-shaped organic semiconducting small molecules containing the
      relatively unexplored thieno[3,2- b]pyrrole with thiophene and furan flanked
      benzothiadiazole. Theoretical insights gained by DFT calculations, supported by
      single crystal structures show that furan flanked benzothiadiazole-thieno[3,2-
      b]pyrrole small molecule has a higher curvature compared to the thiophene flanked
      small molecule due to the shorter carbon-oxygen bond in furan. Despite similar
      optical and electrochemical properties, thiophene flanked small molecule shows
      average hole mobility up to 8 * 10-2 cm2 V-1 s-1, however furan flanked small
      molecule performs poorly in thin film transistor devices (MUh ~ 5 * 10-6 cm2 V-1
      s-1). The drastic difference in hole mobilities was due to the annealing-induced
      crystallinity which was demonstrated by the out-of-plane grazing incidence X-ray
      diffraction and surface morphology studies by tapping mode atomic force
      microscopy analysis.

PMID- 29584399
TI  - Targeted Quantification of Phosphorylation Dynamics in the Context of EGFR-MAPK
      Pathway.
AB  - Large-scale phosphoproteomics with coverage of over 10,000 sites of
      phosphorylation have now been routinely achieved with advanced mass spectrometry
      (MS)-based workflows. However, accurate targeted MS-based quantification of
      phosphorylation dynamics, an important direction for gaining quantitative
      understanding of signaling pathways or networks, has been much less investigated.
      Herein, we report an assessment of the targeted workflow in the context of signal
      transduction pathways, using the epidermal growth factor receptor (EGFR)-mitogen
      activated protein kinase (MAPK) pathway as our model. A total of 43
      phosphopeptides from the EGFR-MAPK pathway were selected for the study. The
      recovery and sensitivity of two commonly used enrichment methods, immobilized
      metal affinity chromatography (IMAC) and titanium oxide (TiO2), combined with
      selected reaction monitoring (SRM)-MS were evaluated. The recovery of
      phosphopeptides by IMAC and TiO2 enrichment was quantified to be 38 +/- 5% and 58
      +/- 20%, respectively, based on internal standards. Moreover, both enrichment
      methods provided comparable sensitivity from 1 to 100 MUg starting peptides.
      Robust quantification was consistently achieved for most targeted phosphopeptides
      when starting with 25-100 MUg peptides. However, the numbers of quantified
      targets significantly dropped when peptide samples were in the 1-25 MUg range.
      Finally, IMAC-SRM was applied to quantify signaling dynamics of EGFR-MAPK pathway
      in Hs578T cells following 10 ng/mL EGF treatment. The kinetics of phosphorylation
      clearly revealed early and late phases of phosphorylation, even for very low
      abundance proteins. These results demonstrate the feasibility of robust targeted
      quantification of phosphorylation dynamics for specific pathways, even starting
      with relatively small amounts of protein.

PMID- 29584402
TI  - Organic Solvent as Internal Standards for Quantitative and High-Throughput Liquid
      Interfacial SERS Analysis in Complex Media.
AB  - Liquid-state interfacial nanoparticle arrays for surface-enhanced Raman
      scattering (SERS) promises a practical, substrate-free, and rapid analysis but
      faces a great challenge to develop a batch and uniform fabrication strategy with
      stable internal standards (IS) because of the difficulties in precisely locating
      both the IS tags and analytes in the same local structure under the harsh
      conditions of biphasic liquid interface. Here, we develop a fast batch
      preparation of self-ordered dense Au nanoparticle (GNP) arrays on
      cyclohexane/water biphasic interface in 96-well plates with the assist of acetone
      as the phase-crossing inducer. The acetone can extract the pesticide molecules
      via a simple dipping sample peels and can rapidly capture and locate the
      pesticide molecule into the plasmonic hotspots. Meanwhile, this phase-crossing
      solvent, acetone itself, generates stable SERS signal and is used as the IS tags
      to calibrate the signal fluctuation. This platform presents an excellent
      uniformity with a relative standard deviation (RSD) of 5.9% compared to the RSD
      of 14.5% without the IS's correction and a good sensitivity with a limit of
      detection (LOD) of 1 nM thiram. This high-throughput strategy for analyzing
      pesticide residues at fruit peels reached detection levels of nanograms per
      square centimeter (ng/cm2). Combined with the 96-well plates, this platform
      greatly facilitates the self-assembly and multiplex sampling. The self-ordered
      arrays at two immiscible phases interface evidenced the detection of both the oil
      soluble thiabendazole and the water-soluble thiram molecules and also realized
      the multiplex and two-phase detection of these two pesticides. This platform
      offers vast possibilities for on-site sensing of various analytes and paves a new
      way for the quantitative and high-throughput SERS analyzer just as convenient as
      the microplate reader.

PMID- 29584404
TI  - Dual-Valve and Counter-Flow Surface Plasmon Resonance.
AB  - Two six-port injector valves and one selector valve commonly used in flow
      injection analysis are combined with a surface plasmon resonance (SPR) instrument
      wherein solutions introduced from the two inlets counter-flow inside the flow
      cell. The system is versatile as the same or different solutions can be rapidly
      and repeatedly introduced to the two fluidic channels in series or in parallel.
      Unlike most commercial SPR instruments employing a single injector valve,
      solutions separately injected from the two injector valves can be readily
      exchanged (<1 s) between the two channels. This new method, referred to as the
      alternate injection mode, not only saves analysis time but also facilitates
      efficient and facile surface reactions for ligand immobilization and prevents
      immobilized species from desorbing. These advantages are demonstrated with the
      measurements of binding of acetazolamide (222.2 Da) to histidine-tagged human
      carbonic anhydrase II (his-tagged HCA). Amine-containing residues of his-tagged
      HCA molecules tethered at Ni-nitrilotriacetic acid (NTA) sensors were rapidly
      cross-linked to the underlying carboxymethylated dextran. The higher ligand
      densities and more stable surfaces are essential for SPR detection of small
      molecule binding. In a different application, microglobulin solutions of
      increasing concentrations were introduced for continuous binding to the
      preimmobilized antibody. The kinetic and affinity measurements can be conducted
      without performing repeated dissociation and surface regeneration reactions.

PMID- 29584406
TI  - Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses.
AB  - Synthetic biology studies aim to develop cellular devices for biomedical
      applications. These devices, based on living instead of electronic or
      electromechanic technology, might provide alternative treatments for a wide range
      of diseases. However, the feasibility of these devices depends, in many cases, on
      complex genetic circuits that must fulfill physiological requirements. In this
      work, we explored the potential of multicellular architectures to act as an
      alternative to complex circuits for implementation of new devices. As a proof of
      concept, we developed specific circuits for insulin or glucagon production in
      response to different glucose levels. Here, we show that fundamental features,
      such as circuit's affinity or sensitivity, are dependent on the specific
      configuration of the multicellular consortia, providing a method for tuning these
      properties without genetic engineering. As an example, we have designed and built
      circuits with an incoherent feed-forward loop architecture (FFL) that can be
      easily adjusted to generate single pulse responses. Our results might serve as a
      blueprint for future development of cellular devices for glycemia regulation in
      diabetic patients.

PMID- 29584407
TI  - Polyelectrolyte Complex Inclusive Biohybrid Microgels for Tailoring Delivery of
      Copigmented Anthocyanins.
AB  - This study fabricated a novel biohybrid microgel containing polysaccharide-based
      polyelectrolyte complexes (PECs) for anthocyanins. Herein, anthocyanins were
      encapsulated into PECs composed of chondroitin sulfate and chitosan, followed by
      incorporation into alginate microgels using emulsification/internal gelation
      method. We demonstrated that PECs incorporation strongly affected the properties
      of microgels, dependent on the polysaccharide concentration and pH in which they
      were fabricated. The dense internal network surrounded by an alginate shell was
      clearly visualized in cross-sectioned PECs-microgels. Stability studies carried
      out under varying ionic strength and pH conditions demonstrated the stimuli
      responsiveness of the PECs-microgels. Additionally, the presence of PECs
      conferred microgels with high rigidity during freeze-drying and excellent
      reconstitution capacity upon rehydration. These observations were attributed to
      the modulation of electrostatic and hydrogen-bonding cross-linking between PECs
      and the alginate gel matrix and suggest the PECs inclusive microgels hold promise
      as delivery vehicles for the controlled release of hydrophilic bioactive
      compounds.

PMID- 29584408
TI  - Seasonal Dynamics of Glyphosate and AMPA in Lake Greifensee: Rapid Microbial
      Degradation in the Epilimnion During Summer.
AB  - Occurrence and fate of glyphosate, a widely used herbicide, and its main
      metabolite AMPA was investigated in Lake Greifensee, Switzerland. Monthly
      vertical concentration profiles in the lake showed an increase of glyphosate
      concentrations in the epilimnion from 15 ng/L in March to 145 ng/L in July,
      followed by a sharp decline to <5 ng/L in August. A similar pattern was observed
      for AMPA. Concentrations of glyphosate and AMPA in the two main tributaries
      generally were much higher than in the lake. Simulations using a numerical lake
      model indicated that a substantial amount of glyphosate and AMPA dissipated in
      the epilimnion, mainly in July and August, with half-lives of only ~2-4 days
      which is ?100 times faster than in the preceding months. Fast dissipation
      coincided with high water temperatures and phytoplankton densities, and low
      phosphate concentrations. This indicates that glyphosate might have been used as
      an alternative phosphorus source by bacterio- and phytoplankton. Metagenomic
      analysis of lake water revealed the presence of organisms known to be capable of
      degrading glyphosate and AMPA.

PMID- 29584409
TI  - The Structural Basis of Calcium-Dependent Inactivation of the Transient Receptor
      Potential Vanilloid 5 Channel.
AB  - The transient receptor potential vanilloid channel subfamily member 5 (TRPV5) is
      a highly selective calcium ion channel predominately expressed in the kidney
      epithelium that plays an essential role in calcium reabsorption from renal
      infiltrate. In order to maintain Ca2+ homeostasis, TRPV5 possesses a tightly
      regulated negative feedback mechanism, where the ubiquitous Ca2+ binding protein
      calmodulin (CaM) directly binds to the intracellular TRPV5 C-terminus, thus
      regulating TRPV5. Here we report on the characterization of the TRPV5 C-terminal
      CaM binding site and its interaction with CaM at an atomistic level. We have
      solved the de novo solution structure of the TRPV5 C-terminus in complex with a
      CaM mutant, creating conditions that mimic the cellular basal Ca2+ state. We
      demonstrate that under these conditions the TRPV5 C-terminus is exclusively bound
      to the CaM C-lobe only, while it confers conformational freedom to the CaM N
      lobe. We also show that at elevated calcium levels, additional interactions
      between the TRPV5 C-terminus and CaM N-lobe occur, resulting in formation of a
      tight 1:1 complex, effectively making the N-lobe the calcium sensor. Together,
      these data are consistent with and support the novel model for Ca2+/CaM-dependent
      inactivation of TRPV channels as proposed by Bate and co-workers [ Bate , N. , et
      al. ( 2018 ) Biochemistry , ( 57), DOI: 10.1021/acs.biochem.7b01286 ].

PMID- 29584410
TI  - A Universal Approach to Render Nanomedicine with Biological Identity Derived from
      Cell Membranes.
AB  - Biomimetic nanoengineering built through integrating the specific cell membrane
      with artificially synthetic nanomedicines represents one of the most promising
      directions for the actualization of personalized therapy. For addressing the
      technical hurdle against the development of this biomimetic technology, the
      present report describes the in-depth exploration and optimization over each
      critical preparation step, including establishment of a nanoparticle-stabilized
      dispersion system, cargo loading, membrane coating, and product isolation.
      Magnetic iron oxide nanoparticles loaded with DOX is used as a typical model for
      the coating with cancer cell membranes, providing compact DNP@CCCM nanostructure
      well-characterized by various techniques. Furthermore, the feasibility of this
      optimized approach in constructing biomimetic membrane-coated nanomedicines has
      been validated on the basis of the remarkably improved biofunctions, such as the
      targetability, magnetic property, hemolysis risk, macrophage evasion, in vitro
      cytotoxicity, in vivo circulation duration, and in vivo principal component
      analysis postinjection. We hope this study regarding technique optimization will
      prompt the advancement of biomembrane-camouflaged nanoparticles as a newly
      emerging biomimetic technology.

PMID- 29584412
TI  - The Academic Office Visit.

PMID- 29584411
TI  - Targeting Dependency on the GPX4 Lipid Peroxide Repair Pathway for Cancer
      Therapy.

PMID- 29584413
TI  - Correction to Uncovering the Determinants of a Highly Perturbed Tyrosine p Ka in
      the Active Site of Ketosteroid Isomerase.

PMID- 29584415
TI  - Hollow Anatase TiO2 Octahedrons with Exposed High-Index {102} Facets for Improved
      Dye-Sensitized Photoredox Catalysis Activity.
AB  - The high activity of exposed facets and large surface area have significant
      effects on the performance of photocatalysts because most of the photoreactivity
      properties of materials are related to surface processes. The strategy of
      combining high-index facets and a hollow structure into one material will provide
      a new way for designing effective photocatalysts, possessing active exposed
      facets and a large surface area at the same time. However, fabricating one
      material with both high-index facets and a hollow structure is still a great
      challenge due to their thermodynamic instability. Here, hollow anatase TiO2
      octahedrons exposed with high-index (102) facets (HTO-102) were successfully
      fabricated for the first time by a facile hydrothermal method using HF and H2O2
      as morphology controlling agents. Compared with two other catalysts (a solid
      sharp octahedron with (101) facets (SSO-101) and a hollow sharp octahedron with
      (101) facets (HSO-101)), HTO-102 particles exhibit a better photochemical
      activity for the selective aerobic oxidation of organic sulfides under visible
      light irradiation. Experimental results and theoretical calculations indicate
      that the excellent photocatalytic activity of HTO-102 particles is mainly due to
      the synergistic effects of its hollow structure and exposed high-index (102)
      facets.

PMID- 29584416
TI  - Photoswitchable Micelles for the Control of Singlet-Oxygen Generation in
      Photodynamic Therapies.
AB  - Inadvertent photosensitizer-activation and singlet-oxygen generation hampers
      clinical application of photodynamic therapies of superficial tumors or
      subcutaneous infections. Therefore, a reversible photoswitchable system was
      designed in micellar nanocarriers using ZnTPP as a photosensitizer and BDTE as a
      photoswitch. Singlet-oxygen generation upon irradiation didnot occur in closed
      switch micelles with ZnTPP/BDTE feeding ratios >1:10. Deliberate switch
      closure/opening within 65-80 min was possible through thin layers of porcine
      tissue in vitro, increasing for thicker layers. Inadvertent opening of the switch
      by simulated daylight, took several tens of hours. Creating deliberate cell
      damage and prevention of inadvertent damage in vitro and in mice could be done at
      lower ZnTPP/BDTE feeding ratios (1:5) in open-switch micelles and at higher
      irradiation intensities than inferred from chemical clues to generate singlet
      oxygen. The reduction of inadvertent photosensitizer activation in micellar
      nanocarriers, while maintaining the ability to kill tumor cells and infectious
      bacteria established here, brings photodynamic therapies closer to clinical
      application.

PMID- 29584417
TI  - Exploiting Ring-Opening Aminolysis-Condensation as a Polymerization Pathway to
      Structurally Diverse Biobased Polyamides.
AB  - A pathway to biobased polyamides (PAs) via ring-opening aminolysis-condensation
      (ROAC) under benign conditions with diverse structure was designed. Ethylene
      brassylate (EB), a plant oil-derived cyclic dilactone, was used in combination
      with an array of diamines of diverse chemical structure, and ring-opening of the
      cyclic dilactone EB was revealed as a driving force for the reaction. The ROAC
      reactions were adjusted, and reaction conditions of 100  degrees C under
      atmospheric pressure using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a
      catalyst for 24 h were optimal. The structures of the polyamides were confirmed
      by mass spectroscopy, FTIR, and NMR, and the PAs had viscosity average molecular
      weights ( Meta) of ~5-8 kDa. Glassy or semicrystalline PAs with glass transition
      temperatures between 48 and 55  degrees C, melting temperatures of 120-200 
      degrees C for the semicrystalline PAs, and thermal stabilities above 400  degrees
      C were obtained and were comparable to the existing PAs with similar structures.
      As a proof-of-concept of their usage, one of the PAs was shown to form fibers by
      electrospinning and films by melt pressing. Compared to conventional methods for
      PA synthesis, the ROAC route portrayed a reaction temperature at least 60-80 
      degrees C lower, could be readily carried out without a low-pressure environment,
      and eliminated the use of solvents and toxic chemicals. Together with the plant
      oil-derived monomer (EB), the ROAC route provided a sustainable alternative to
      design biobased PAs.

PMID- 29584419
TI  - A Comparative Proteome Approach Reveals Metabolic Changes Associated with
      Flammulina velutipes Mycelia in Response to Cold and Light Stress.
AB  - In some industrial processes, cold and light stresses are recognized as two
      important environmental triggers for the transformation of mycelia into fruit
      bodies via intermediate primordia in Flammulina velutipes cultivation. To gain
      insights into the mechanism of regulation of F. velutipes mycelia in response to
      cold and light stress, proteins expressed abundantly and characteristically at
      particular stress states were investigated by using the isobaric tags for the
      relative and absolute quantitation labeling technique. Among the 1046
      nonredundant proteins identified with a high degree of confidence, 264 proteins,
      which were detected as differentially expressed proteins, were associated with
      176 specific KEGG pathways. In-depth data analysis revealed that the regulatory
      network underlying the cold and light response mechanisms of F. velutipes mycelia
      was complex and multifaceted, as it included varied functions such as rapid
      energy supply, the biosynthesis of lysine, phenylalanine, tyrosine, and gamma
      aminobutyric acid, the calcium signal transduction process, dynein-dependent
      actin and microtubule cytoskeleton formation, autolysis, oxidative stress
      adaptation, pigment secretion, tissue and organ morphogenesis, and other
      interesting stress-related processes. Insights into the proteins might shed light
      on an intuitive understanding of the cold and light stress response mechanism
      underlying the fruiting processes of F. velutipes. Furthermore, the data might
      also provide further insights into the stress response mechanism of macro-fungi
      and valuable information for scientific improvement of some mushroom cultivation
      techniques in practice.

PMID- 29584421
TI  - Benzoxazole-Linked Ultrastable Covalent Organic Frameworks for Photocatalysis.
AB  - The structural uniqueness of covalent organic frameworks (COFs) has brought these
      new materials great potential for advanced applications. One of the key aspects
      yet to be developed is how to improve the robustness of covalently linked
      reticular frameworks. In order to make the best use of pi-conjugated structures,
      we develop herein a "killing two birds with one stone" strategy and construct a
      series of ultrastable benzoxazole-based COFs (denoted as LZU-190, LZU-191, and
      LZU-192) as metal-free photocatalysts. Benefiting from the formation of
      benzoxazole rings through reversible/irreversible cascade reactions, the
      synthesized COFs exhibit permanent stability in the presence of strong acid (9 M
      HCl), strong base (9 M NaOH), and sunlight. Meanwhile, reticulation of the
      benzoxazole moiety into the pi-conjugated COF frameworks decreases the optical
      band gap and therefore increases the capability for visible-light absorption. As
      a result, the excellent photoactivity and unprecedented recyclability of LZU-190
      (for at least 20 catalytic runs, each with a product yield of 99%) have been
      illustrated in the visible-light-driven oxidative hydroxylation of arylboronic
      acids to phenols. This contribution represents the first report on the
      photocatalytic application of benzoxazole-based structures, which not only sheds
      new light on the exploration of robust organophotocatalysts from small molecules
      to extended frameworks but also offers in-depth understanding of the structure
      activity relationship toward practical applications of COF materials.

PMID- 29584422
TI  - Development of Certified Matrix-Based Reference Material as a Calibrator for
      Genetically Modified Rice G6H1 Analysis.
AB  - The accurate monitoring and quantification of genetically modified organisms
      (GMOs) are key points for the implementation of labeling regulations, and a
      certified reference material (CRM) acts as the scaleplate for quantifying the GM
      contents of foods/feeds and evaluating a GMO analytical method or equipment.
      Herein we developed a series of CRMs for transgenic rice event G6H1, which
      possesses insect-resistant and herbicide-tolerant traits. Three G6H1 CRMs were
      produced by mixing seed powders obtained from homozygous G6H1 and its recipient
      cultivar Xiushui 110 at mass ratios of 49.825%, 9.967%, and 4.986%. The between
      bottle homogeneity and within-bottle homogeneity were thoroughly evaluated with
      consistent results. The potential DNA degradation in transportation and shelf
      life were evaluated with an expiration period of at least 12 months. The property
      values of three CRMs (G6H1a, G6H1b, G6H1c) were given as (49.825 +/- 0.448) g/kg,
      (9.967 +/- 1.757) g/kg, and (4.986 +/- 1.274 g/kg based on mass fraction ratio,
      respectively. Furthermore, the three CRMs were characterized with values of (5.01
      +/- 0.08)%, (1.06 +/- 0.22)%, and (0.53 +/- 0.11)% based on the copy number ratio
      using the droplet digital PCR method. All results confirmed that the produced
      G6H1 matrix-based CRMs are of high quality with precise characterization values
      and can be used as calibrators in GM rice G6H1 inspection and monitoring and in
      evaluating new analytical methods or devices targeting the G6H1 event.

PMID- 29584423
TI  - Ambient Nonmethane Hydrocarbon Levels Along Colorado's Northern Front Range:
      Acute and Chronic Health Risks.
AB  - Oil and gas (O&G) facilities emit air pollutants that are potentially a major
      health risk for nearby populations. We characterized prenatal through adult
      health risks for acute (1 h) and chronic (30 year) residential inhalation
      exposure scenarios to nonmethane hydrocarbons (NMHCs) for these populations. We
      used ambient air sample results to estimate and compare risks for four
      residential scenarios. We found that air pollutant concentrations increased with
      proximity to an O&G facility, as did health risks. Acute hazard indices for
      neurological (18), hematological (15), and developmental (15) health effects
      indicate that populations living within 152 m of an O&G facility could experience
      these health effects from inhalation exposures to benzene and alkanes. Lifetime
      excess cancer risks exceeded 1 in a million for all scenarios. The cancer risk
      estimate of 8.3 per 10 000 for populations living within 152 m of an O&G facility
      exceeded the United States Environmental Protection Agency's 1 in 10 000 upper
      threshold. These findings indicate that state and federal regulatory policies may
      not be protective of health for populations residing near O&G facilities. Health
      risk assessment results can be used for informing policies and studies aimed at
      reducing and understanding health effects associated with air pollutants emitted
      from O&G facilities.

PMID- 29584424
TI  - Controlling the Recognition and Reactivity of Alkyl Ammonium Guests Using an
      Anion Coordination-Based Tetrahedral Cage.
AB  - Caged structures have found wide application in a variety of areas, including
      guest encapsulation and catalysis. Although metal-based cages have dominated the
      field, anion-coordination-based cages are emerging as a new type of
      supramolecular ensemble with interesting host-guest properties. In the current
      work, we report a C3-symmetric tris-bis(urea) ligand based on the 2,4,6-triphenyl
      1,3,5-triazine spacer, which assembles with phosphate anions to form an A4L4-type
      (A = anion, L = ligand) tetrahedral cage, 3, with unusually high packing
      coefficients (up to 99.5% for the best substrate). Cage 3 is able to adjust its
      size and shape (from 136 to 216 A3) by bending of the triphenyltriazine plane.
      This allows it to accommodate relatively large guests. In the case of DABCO,
      inclusion within the cage allows the degree of methylation to be controlled and
      the monomethylated product to be isolated cleanly under conditions where mixtures
      of the mono- and dimethylated adduct are obtained in the absence of cage 3.

PMID- 29584425
TI  - Leucine Promotes the Growth of Fetal Pigs by Increasing Protein Synthesis through
      the mTOR Signaling Pathway in Longissimus Dorsi Muscle at Late Gestation.
AB  - Leucine (Leu) plays an important role in protein synthesis and metabolism. The
      present study tested whether Leu supplementation in the diet for sows during late
      pregnancy could improve piglet birth weight, and it also investigated the
      possible underlying mechanism. Two hundred sows at day 70 of pregnancy were
      selected and assigned to four groups fed with following four diets until
      farrowing, respectively: corn and soybean meal-based diet group (CON), CON +
      0.40% Leu, CON + 0.80% Leu, and CON + 1.20% Leu. We found that supplementing with
      0.80% Leu significantly increased mean piglet birth weight ( P < 0.05).
      Supplementation with 0.40, 0.80, and 1.20% Leu increased the plasma concentration
      of Leu, while decreasing the plasma concentrations of valine (Val) and isoleucine
      (Ile) in both farrowing sows and newborn piglets ( P < 0.05). The protein
      expressions of amino acid transporters (including LAT1, SNAT1, SNAT2, 4F2hc, and
      rBAT) in duodenum, jejunum, ileum, longissimus dorsi muscle of newborn piglets,
      and placenta of sows showed a difference among the CON group and Leu supplemented
      groups. Expressions of p-mTOR, p-4E-BP1, and p-S6K1 in longissimus dorsi muscle
      were also enhanced in each of the supplemental Leu groups compared to CON ( P <
      0.05). Collectively, these results indicated that 0.40-0.80% Leu supplementation
      during late gestation enhanced birth weight of fetal pigs by increasing protein
      synthesis through modulation of the plasma amino acids profile, amino acid
      transporters expression, and mTOR signaling pathway.

PMID- 29584427
TI  - Simplified Submission Requirements for Authors of JACS Communications.

PMID- 29584426
TI  - miRNA and mRNA Expression Profiles Reveal Insight into Chitosan-Mediated
      Regulation of Plant Growth.
AB  - Chitosan has been numerously studied as a plant growth regulator and stress
      tolerance inducer. To investigate the roles of chitosan as bioregulator on plant
      and unravel its possible metabolic responses mechanisms, we simultaneously
      investigated mRNAs and microRNAs (miRNAs) expression profiles of wheat seedlings
      in response to chitosan heptamer. We found 400 chitosan-responsive differentially
      expressed genes, including 268 up-regulated and 132 down-regulated mRNAs, many of
      which were related to photosynthesis, primary carbon and nitrogen metabolism,
      defense responses, and transcription factors. Moreover, miRNAs also participate
      in chitosan-mediated regulation on plant growth. We identified 87 known and 21
      novel miRNAs, among which 56 miRNAs were induced or repressed by chitosan
      heptamer, such as miRNA156, miRNA159a, miRNA164, miRNA171a, miRNA319, and
      miRNA1127. The integrative analysis of miRNA and mRNA expression profiles in this
      case provides fundamental information for further investigation of regulation
      mechanisms of chitosan on plant growth and will facilitate its application in
      agriculture.

PMID- 29584428
TI  - Flowerlike Mg(OH)2 Cross-Nanosheets for Controlling Cry1Ac Protein Loss:
      Evaluation of Insecticidal Activity and Biosecurity.
AB  - Bacillus thuringiensis (Bt) can produce Cry proteins during the sporulation
      phase, and Cry protein is effective against lepidopteran, coleopteran, and
      dipteran insects and nematodes. However, Cry protein tends to be discharged into
      soil and nontarget plants through rainwater runoff, leading to reduced effective
      period toward target insects. In the present study, nano-Mg(OH)2 (magnesium
      hydroxide nanoparticles, MHNPs) were synthesized to control the loss of Cry1Ac
      protein and deliver protein to Helicoverpa armigera (Lepidoptera: Noctuidae). The
      results showed that Cry1Ac protein could be loaded onto MHNPs through
      electrostatic adsorption, and both MHNPs and Cry protein were stable during the
      adsorption process. Meanwhile, the Cry1Ac-loaded MHNPs could remain on the
      surface of cotton leaves, resulting in enhanced adhesion of Cry1Ac protein by
      59.50% and increased pest mortality by 75.00%. Additionally, MHNPs could be
      slowly decomposed by acid medium and MHNPs showed no obvious influence on cotton,
      Bt, Escherichia coli, and H. armigera. Therefore, MHNPs could serve as an
      efficient nanocarrier for delivery of Cry1Ac protein and be used as a potential
      adjuvant for biopesticide in agricultural applications.

PMID- 29584429
TI  - Qualitative Study on the Production of the Allelochemicals Benzoxazinones by
      Inducing Polyploidy in Gramineae with Colchicine.
AB  - The possibility of inducing polyploidy in grasses by treatment with colchicine
      and its effect on the production and root exudate content of 2,4-dihydroxy-7
      methoxy-2 H-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-2 H-benzoxazin-3-one
      (DIBOA) was studied in wheat, corn, and rye. Caryopses treated with colchicine at
      concentrations in the range of 0.1-10 mg/mL for 8 and 48 h and with inoculation
      of the growth medium are markedly affected in terms of both the distribution and
      concentration levels of allelochemicals in plants. A greater accumulation was
      observed in the root with respect to the stem, and this increased with an
      increasing concentration of colchicine and with treatment time. Analysis of the
      compounds released by root exudates showed that treatment with colchicine at a
      concentration higher than 1 mg/mL caused a significant increase in the
      concentrations of allelochemicals measured in the growth medium. It is proposed
      that treatment with colchicine of seedling caryopses mixoploids plant populations
      and that the overall effect is an increase in the levels of allelochemicals
      released. The ecological implications of this behavior are discussed along with
      the impact of plant-plant interactions (allelopathy).

PMID- 29584430
TI  - Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1
      Proteins.
AB  - A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2
      proteins that regulate apoptosis of cancer cells. Specific inhibition of the
      BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer
      cells by shortening the peptide to 14 residues, inserting two cyclization
      constraints to stabilize a water-stable alpha-helix, and incorporating an N
      terminal acrylamide electrophile for selective covalent bonding to Bcl2A1. Mass
      spectrometry of trypsin-digested bands on electrophoresis gels established
      covalent bonding of an electrophilic helix to just one of the three cysteines in
      Bcl2A1, the one (Cys55) at the BimBH3-Bcl2A1 protein-protein interaction
      interface. Optimizing the helix-inducing constraints and the sequence
      subsequently enabled electrophile removal without loss of inhibitor potency. The
      bicyclic helical peptides were potent, cell permeable, plasma-stable, dual
      inhibitors of Bcl2A1 and Mcl-1 with high selectivity over other Bcl2 proteins.
      One bicyclic peptide was shown to inhibit the interaction between a pro-apoptotic
      protein (Bim) and either endogenous Bcl2A1 or Mcl-1, to induce apoptosis of
      SKMel28 human melanoma cells, and to sensitize them for enhanced cell death by
      the anticancer drug etoposide. These approaches look promising for chemically
      silencing intracellular proteins.

PMID- 29584431
TI  - Structure Evolution and Drying Dynamics in Sliding Cholesteric Cellulose
      Nanocrystals.
AB  - The study of colloidal liquid crystals (LCs) reveals fundamental insights into
      the nature of ordered materials, giving rise to emergent properties with
      fascinating applications in soft matter nanotechnology. Here we investigate the
      shape instabilities, layer undulations, dynamic assembly, and collective
      behaviors in evaporating a cellulose nanocrystal-based cholesteric LC drop.
      During the drying process, the drop edges are pinned to the substrate with
      spontaneous convective flow occurring along the drop, which leads to
      nonequilibrium sliding of the individual cholesteric fragment with active
      ordering as well as hydrodynamic fluctuations and flow transitions in the bulk
      cholesteric phase.

PMID- 29584432
TI  - Quantum Mechanics Study on Hydrophilic and Hydrophobic Interactions in the
      Trivaline-Water System.
AB  - With the aim to elucidate hydrophobic effects in the unfolded state of peptides,
      DFT-M062X computations on the Val3H+. nH2O ( n up to 22) clusters have been
      accomplished. As far as the main chain is concerned, four conformers with beta
      strand and/or polyproline type II conformations, PPII (indicated as beta-beta,
      beta-PPII, PPII-beta, and PPII-PPII), have been found by changing the phi and psi
      angles. For bare peptide, the side chain (isopropyl) of each residue can
      independently take on three different orientations with negligible effects on
      energetics. The great isopropyl spatial separations in beta-beta and beta-PPII
      conformers allow for the construction of synergic and extensive water-water and
      water-peptide H-bonding in the minimal hydration Val3H+.22H2O models without
      significant steric encumbrance. Conversely, due to the proximity of the isopropyl
      of the central residue with the other two, some restrictions in the water shell
      construction around the peptide become evident for the PPII-PPII conformer and
      the number of energetically accessible structures decreases. This is indicative
      of correlated motion involving isopropyls and backbone mediated by water
      molecules, the origin of the nearest neighbor effects. Comparing the
      thermodynamic data of Ala3H+.22H2O and Val3H+.22H2O, what emerges is that both
      hydration enthalpy and entropy drive the beta-strand stability of the latter.

PMID- 29584433
TI  - Online Optimization of Total Acceptance in Hamiltonian Replica Exchange
      Simulations.
AB  - Replica exchange is a widely used sampling strategy in molecular simulation.
      While a variety of methods exist to optimize parameters for temperature replica
      exchange, less is known about how to optimize parameters for more general
      Hamiltonian replica exchange simulations. We present an algorithm for the online
      optimization of total acceptance for both temperature and Hamiltonian replica
      exchange simulations using stochastic gradient descent. We optimize the total
      acceptance, a heuristic objective function capturing the efficiency of replica
      exchange. Our approach is general and has several desirable properties,
      including: (1) it makes few assumptions about the system of interest, (2)
      optimization occurs online without the requirement of presimulation, and (3) most
      importantly, it readily generalizes to systems where there are multiple control
      parameters (e.g., temperatures, force constants, etc.) that determine the
      Hamiltonian of each replica. We explore some general properties of the algorithm
      on a simple harmonic oscillator system, and demonstrate its effectiveness on a
      more complex data-guided protein folding simulation.

PMID- 29584434
TI  - Boryl Radicals-Triggered Selective C-H Functionalization for the Synthesis of
      Diverse Phenanthridine Derivatives.
AB  - A boryl radical-triggered C-H functionalization of aliphatic ethers/amines or DMF
      with isocyanides is developed to deliver diverse phenanthridine derivatives in
      good to excellent yields. The substrate scope is broad, and a wide range of
      functional groups are tolerated under the standard conditions. The rapid removal
      of HBPin species by 4-cyanopyridine 1-oxide provides the driving force for this
      reaction. This new method should make boryl radicals widely applicable in organic
      synthesis.

PMID- 29584435
TI  - Thermochemistry, Tautomerism, and Thermal Decomposition of 1,5-Diaminotetrazole:
      A High-Level ab Initio Study.
AB  - Thermochemistry, kinetics, and mechanism of thermal decomposition of 1,5
      diaminotetrazole (DAT), a widely used "building block" of nitrogen-rich energetic
      compounds, were studied theoretically at a high and reliable level of theory
      (viz., using the explicitly correlated CCSD(T)-F12/aug-cc-pVTZ procedure).
      Quantum chemical calculations provided detailed insight into the thermolysis
      mechanism of DAT missing in the existing literature. Moreover, several
      contradictory assumptions on the mechanism and key intermediates of thermolysis
      were resolved. The unimolecular primary decomposition reactions of the seven
      isomers of DAT were studied in the gas phase and in the melt using a simplified
      model of the latter. The two-step reaction of N2 elimination from the diamino
      tautomer was found to be the primary decomposition process of DAT in the gas
      phase and melt. The effective Arrhenius parameters of this process were
      calculated to be E a = 43.4 kcal mol-1 and log( A/s-1) = 15.2 in a good agreement
      with the experimental values. Contrary to the existing literature data, all other
      decomposition channels of DAT isomers turned out to be kinetically unimportant.
      Apart from this, a new primary decomposition channel yielding N2, cyanamide, and
      1,1-diazene was found for some H-bonded dimers of DAT. We also determined a
      reliable and mutually consistent set of thermochemical values for DAT (Delta f H
      solid0 = 74.5 +/- 1.5 kcal.mol-1) by combining theoretically calculated (W1
      multilevel procedure along with an isodesmic reaction) gas phase enthalpy of
      formation (Delta f H gas0 = 100.7 +/- 1.0 kcal.mol-1) and experimentally measured
      sublimation enthalpy (Delta sub H0 = 26.2 +/- 0.5 kcal.mol-1).

PMID- 29584436
TI  - Can Storage Time Improve the Physical Stability of Amorphous Pharmaceuticals with
      Tautomerization Ability Exposed to Compression? The Case of a Chloramphenicol
      Drug.
AB  - In this article we thoroughly investigated the physical stability of the
      amorphous form of a chloramphenicol drug. The tendency toward recrystallization
      of this drug has been examined (i) at nonisothermal conditions by means of a DSC
      technique; (ii) at isothermal conditions and temperature close to Troom by means
      of dielectric spectroscopy; (iii) at isothermal conditions and elevated
      temperatures of T = 323 K and 338 K by dielectric spectroscopy; and (iv) at
      conditions imitating the manufacturing procedure (i.e., elevated temperature and
      compression procedure). Our investigations have shown that amorphous
      chloramphenicol, stored at both standard storage and elevated temperature
      conditions, does not reveal a tendency toward recrystallization. However,
      compression significantly changes this behavior and destabilizes the examined
      compound. We found that due to chemical equilibration of the sample, the
      elongation of the storage time before compression might improve the physical
      stability of the examined pharmaceutical exposed to compression 34-times.

PMID- 29584437
TI  - High Photoinduced Ordering and Controllable Photostability of Hydrophilic
      Azobenzene Material Based on Relative Humidity.
AB  - Azobenzene materials provide an effective way for liquid crystal (LC) alignment
      besides traditional rubbing technology. A strong relationship between relative
      humidity (RH) and the photoalignment quality of hydrophilic azobenzene dye
      brilliant yellow (BY) has been investigated. Good photoalignment quality can only
      be ensured at about 40% RH or below. On the other hand, the photostability of the
      alignment layer is also influenced dramatically by RH. The rewritability can be
      guaranteed at extremely low RH (<=10%). It is gradually lost with increasing RH,
      and the alignment layer becomes photostable against further light exposure when
      at 40% RH or above. Therefore, the BY photoalignment layer can be tuned from
      rewritable to photostable by simply adjusting RH, and thus multistep
      photopatterned alignments can be obtained and reserved based on this method.
      Similar properties are also expected for other hydrophilic azobenzene
      photoalignment materials, where the specific RH values may vary correspondingly.
      The reason is due to the strong intermolecular interaction and J-aggregate
      formation of BY molecules with water insertion. Moreover, the lyotropic LC formed
      by J-aggregated BY molecules in aqueous solution is reported here.

PMID- 29584438
TI  - Ruthenium(II)-Catalyzed Regio- and Stereoselective C-H Allylation of Indoles with
      Allyl Alcohols.
AB  - A ruthenium-catalyzed C-H allylation of indoles with allyl alcohols via beta
      hydroxide elimination is reported. Without external oxidants and expensive
      additives, this reaction features mild reaction conditions, compatibility with
      various functional groups, and good to excellent regioselectivity and
      stereoselectivity.

PMID- 29584439
TI  - Fe-Catalyzed Cycloisomerization of Aryl Allenyl Ketones: Access to 3-Arylidene
      indan-1-ones.
AB  - A cycloisomerization of aryl allenyl ketones to 3-arylidene-indan-1-ones using a
      cationic Fe-complex as a catalyst is reported. The catalyst opens a synthetically
      interesting reaction pathway to this surprisingly underrepresented class of
      indanones that are not accessible using alternative catalytic systems.

PMID- 29584441
TI  - Assembling the Puzzle of Apixaban Solid Forms.
AB  - An in-depth analysis of the solid forms of the anticoagulant drug Apixaban (APX)
      has been conducted to sort out the confusion in the scientific and patent
      literature regarding the solid forms landscape. The nomenclature employed and the
      accompanying characterization data are often unclear and incomplete, leading to a
      situation in which apparently the same form has been reported by different
      authors or claimed by different inventors. A comprehensive solid forms screen and
      a full and careful comparison with the literature data has been performed to draw
      a reliable picture of the solid forms landscape of APX.

PMID- 29584440
TI  - Total Synthesis of Tambromycin Enabled by Indole C-H Functionalization.
AB  - The total synthesis of tambromycin (1), a recently isolated tetrapeptide, is
      reported. This unusual natural product possesses a highly modified tryptophan
      derived indole fragment fused to an alpha-methylserine-derived oxazoline ring,
      and a unique noncanonical amino acid residue named tambroline (11). A convergent
      synthesis of tambromycin was achieved by a 13-step route that leveraged recent
      developments in the field of C-H functionalization to prepare the complex indole
      fragment, as well as an efficient synthesis of tambroline that featured a
      diastereoselective amination of homoproline.

PMID- 29584442
TI  - Drainage from a Fluid-Handling Component with Multiple Orifices due to
      Inclination or Rotation.
AB  - The onset of drainage of liquids from fluid-handling components with two or more
      orifices was evaluated. The components were filled with water, ethylene glycol,
      or ethyl alcohol and oriented vertically with their orifices facing downward. The
      lower end of the components was slowly raised toward the horizon. No flow
      occurred until a critical angle of inclination was reached. The resistance to
      drainage was greatest for small, closely spaced orifices and declined
      precipitously as the size and spacing of the orifices increased. The onset of
      drainage was successfully modeled as a balance between the hydrostatic pressure
      in the bulk liquid and the Laplace pressure of the air-liquid interfaces present
      within the orifices.

PMID- 29584443
TI  - Distribution Control-Oriented Intercalation of a Cationic Metal Complex into
      Layered Silicates Modified with Organosulfonic-Acid Moieties.
AB  - A layered sodium silicate, octosilicate (Na2Si8O17. nH2O), was modified with an
      organosulfonic-acid moiety (sulfonated propyl (SPr) group, sulfonated phenethyl
      (SPhE) group, or sulfonated p-trifluoromethylphenyl (STFPh) group) for use as a
      host material to accommodate a cationic guest, tris(2,2'-bipyridine)ruthenium(II)
      cation ([Ru(bpy)3]2+). The organosulfonic-acid moiety was bound to the silicate
      layer via a reaction of an alkylammonium-exchanged octosilicate with a silane
      coupling agent, and subsequent treatment (oxidation or sulfonation) of the bound
      organosilyl groups; the surface densities of the organosulfonic-acid moiety were
      varied by controlling the added amount of silane coupling agents. Adsorption of
      [Ru(bpy)3]2+ onto surface-modified octosilicates was conducted to find that some
      surface-modified octosilicates successfully adsorbed [Ru(bpy)3]2+ in the
      interlayer space (intercalation), while other surface-modified octosiliates did
      not. In addition, the UV-vis absorption and the luminescence indicate that
      intercalated [Ru(bpy)3]2+ diffused in the interlayer and that the distribution of
      the time-averaged location varied depending on the kind and amount of the
      organosulfonic-acid moieties. Thus, the kind and surface density of the
      organosulfonic-acid moiety, which correlates to the interactions between the
      group and the guest species, the volume of free nanospace for adsorption and
      motion of guests, and the swelling properties, are the key factors not only for
      the intercalation ability but also for the dynamics of the guest in the
      interlayer space.

PMID- 29584444
TI  - Kinetics of Surface-Mediated Fibrillization of Amyloid-beta (12-28) Peptides.
AB  - Surfaces or interfaces are considered to be key factors in facilitating the
      formation of amyloid fibrils under physiological conditions. In this report, we
      study the kinetics of the surface-mediated fibrillization (SMF) of an amyloid
      beta fragment (Abeta12-28) on mica. We employ a spin-coating-based drying
      procedure to control the exposure time of the substrate to a low-concentration
      peptide solution and then monitor the fibril growth as a function of time via
      atomic force microscopy (AFM). The evolution of surface-mediated fibril growth is
      quantitatively characterized in terms of the length histogram of imaged fibrils
      and their surface concentration. A two-dimensional (2D) kinetic model is proposed
      to numerically simulate the length evolution of surface-mediated fibrils by
      assuming a diffusion-limited aggregation (DLA) process along with size-dependent
      rate constants. We find that both monomer and fibril diffusion on the surface are
      required to obtain length histograms as a function of time that resemble those
      observed in experiments. The best-fit simulated data can accurately describe the
      key features of experimental length histograms and suggests that the mobility of
      loosely bound amyloid species is crucial in regulating the kinetics of SMF. We
      determine that the mobility exponent for the size dependence of the DLA rate
      constants is alpha = 0.55 +/- 0.05, which suggests that the diffusion of loosely
      bound surface fibrils roughly depends on the inverse of the square root of their
      size. These studies elucidate the influence of deposition rate and surface
      diffusion on the formation of amyloid fibrils through SMF. The method used here
      can be broadly adopted to study the diffusion and aggregation of peptides or
      proteins on various surfaces to investigate the role of chemical interactions in
      two-dimensional fibril formation and diffusion.

PMID- 29584445
TI  - Protectin DX attenuates LPS-induced inflammation and insulin resistance in
      adipocytes via AMPK-mediated suppression of the NF-kappaB pathway.
AB  - Several studies have demonstrated that protectins, omega-3 fatty acid-derived
      proresolution mediators, may ameliorate inflammation. Recently, protectin DX
      (PDX) was also reported to attenuate inflammation and insulin resistance in
      several cell types. However, the effects of PDX on inflammation in adipocytes
      remain ambiguous. In this study, we found that PDX treatment suppressed
      adipogenesis and lipid accumulation during 3T3-L1 differentiation. Treatment of
      differentiated 3T3-L1 cells with PDX stimulated AMP-activated protein kinase
      (AMPK) phosphorylation in a dose-dependent manner. PDX-induced AMPK
      phosphorylation blocked lipopolysaccharide (LPS)-induced secretion of
      proinflammatory cytokines, such as tumor necrosis factor-alpha and monocyte
      chemoattractant protein-1. Treatment of 3T3-L1 cells with PDX alleviated LPS
      induced NF-kappaB and inhibitory factor kappaB phosphorylation. Furthermore, PDX
      treatment diminished LPS-induced impairment of insulin signaling and insulin
      stimulated glucose uptake, as well as fatty acid oxidation. These effects were
      decreased by silencing AMPK expression with small-interfering RNA. In conclusion,
      the current findings suggest that PDX attenuates inflammation and insulin
      resistance in adipocytes via an AMPK-dependent pathway, which in turn provides
      evidence that PDX has anti-inflammatory and antidiabetic effects in adipocytes.

PMID- 29584446
TI  - The insulin receptor is expressed and functional in cultured blood-brain barrier
      endothelial cells but does not mediate insulin entry from blood to brain.
AB  - Insulin and its receptor are known to be present and functional in the brain.
      Insulin cerebrospinal fluid concentrations have been shown to correlate with
      plasma levels of insulin in a nonlinear fashion, indicative of a saturable
      transport pathway from the blood to the brain interstitial fluid. The aim of the
      present study was to investigate whether insulin was transported across brain
      endothelial cells in vitro via an insulin receptor-dependent pathway. The study
      showed that the insulin receptor was expressed at both the mRNA and protein
      levels in bovine brain endothelial cells. Luminally applied radiolabeled insulin
      showed insulin receptor-mediated binding to the endothelial cells. This caused a
      dose-dependent increase in Akt-phosphorylation, which was inhibited by
      coapplication of an insulin receptor inhibitor, s961, demonstrating activation of
      insulin receptor signaling pathways. Transport of insulin across the blood-brain
      barrier in vitro was low and comparable to that of a similarly sized paracellular
      marker. Furthermore, insulin transport was not inhibited by coapplication of an
      excess of unlabeled insulin or an insulin receptor inhibitor. The insulin
      transport and uptake studies were repeated in mouse brain endothelial cells
      demonstrating similar results. Although it cannot be ruled out that culture
      induced changes in the cell model could have impaired a potential insulin
      transport mechanism, these in vitro data indicate that peripheral insulin must
      reach the brain parenchyma through alternative pathways rather than crossing the
      blood-brain barrier via receptor mediated transcytosis.

PMID- 29584448
TI  - Bio-based edible coatings for the preservation of fishery products: A Review.
AB  - The popularity of preprocessed fresh fishery products such as fillets and peeled
      shrimps is growing in today s market due to their convenience for subsequent
      processing and cooking. However, fishery products are highly perishable because
      of the combined actions of biochemical reactions and microbial metabolism.
      Various methods have been proposed to address this problem. Among these methods,
      bio-based edible coating has been highlighted as a promising solution. This
      review updates and summarizes the recent literature on the application of
      coatings for the preservation of fishery products including the aspects of
      coating carriers, composite natural preservatives and coating methods, and a
      discussion of the protective effects based on microbial, physicochemical and
      sensorial evaluations. Moreover, some challenges and future research directions
      regarding optimization of formulas and exploration of mechanisms of coating are
      also discussed. Given consumer demand for fresh fishery products with long shelf
      life, edible coatings that are environmentally friendly and effective alternative
      will be used to extend the shelf life of fishery products.

PMID- 29584449
TI  - Efficacy of synbiotic supplementation in patients with nonalcoholic fatty liver
      disease: A systematic review and meta-analysis of clinical trials: Synbiotic
      supplementation and NAFLD.
AB  - OBJECTIVE: We systematically reviewed available randomized clinical trials (RCTs)
      to elucidate the overall effects of synbiotic supplementation in patients with
      nonalcoholic fatty liver disease (NAFLD). METHODS: PubMed, Scopus, ISI Web of
      science and Google Scholar were searched up to December, 2017. All RCTs using
      synbiotic supplements to treat NAFLD included in this systematic review and meta
      analysis. Mean Difference (MD) was pooled using a random-effects model. RESULTS:
      Eleven eligible databases from seven RCTs were identified for the present meta
      analysis. Our results showed that synbiotic supplementation can decrease body
      weight, fasting blood sugar, insulin, low density lipoprotein cholesterol, total
      cholesterol, triglyceride, high-sensitivity C-reactive protein, tumor necrosis
      factor alpha, alanine transaminase and aspartate transaminase levels among
      patients with NAFLD. In contrast, synbiotic did not have favorable effects on
      body mass index (BMI), waist circumference, homeostasis model assessment for
      insulin resistance (HOMA-IR), and high density lipoprotein cholesterol (HDL)
      levels compared with the placebo group. CONCLUSION: The current study revealed
      that synbiotic supplementation has favorable effect on inflammatory factors,
      liver enzymes and some anthropometric indices, lipid profiles and glucose
      homeostasis parameters in patients with NAFLD.

PMID- 29584447
TI  - Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review
      and Meta-Analysis.
AB  - RATIONALE: Respiratory muscle weakness is common in critically ill patients; the
      role of targeted inspiratory muscle training (IMT) in intensive care unit
      rehabilitation strategies remains poorly defined. OBJECTIVES: The primary
      objective of the present study was to describe the range and tolerability of
      published methods for IMT. The secondary objectives were to determine whether IMT
      improves respiratory muscle strength and clinical outcomes in critically ill
      patients. METHODS: We conducted a systematic review to identify randomized and
      nonrandomized studies of physical rehabilitation interventions intended to
      strengthen the respiratory muscles in critically ill adults. We searched the
      MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to
      September Week 3, 2017) and conference proceedings (2012 to 2017). Data were
      independently extracted by two authors and collected on a standardized report
      form. RESULTS: A total of 28 studies (N = 1,185 patients) were included. IMT was
      initiated during early mechanical ventilation (8 studies), after patients proved
      difficult to wean (14 studies), or after extubation (3 studies), and 3 other
      studies did not report exact timing. Threshold loading was the most common
      technique; 13 studies employed strength training regimens, 11 studies employed
      endurance training regimens, and 4 could not be classified. IMT was feasible, and
      there were few adverse events during IMT sessions (nine studies; median, 0%;
      interquartile range, 0-0%). In randomized trials (n = 20), IMT improved maximal
      inspiratory pressure compared with control (15 trials; mean increase, 6 cm H2O;
      95% confidence interval [CI], 5-8 cm H2O; pooled relative ratio of means, 1.19;
      95% CI, 1.14-1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm
      H2O; 95% CI, 5-14 cm H2O). IMT was associated with a shorter duration of
      ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8-7.4 d) and a
      shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7
      4.0 d), but confidence in these pooled estimates was low owing to methodological
      limitations, including substantial statistical and methodological heterogeneity.
      CONCLUSIONS: Most studies of IMT in critically ill patients have employed
      inspiratory threshold loading. IMT is feasible and well tolerated in critically
      ill patients and improves both inspiratory and expiratory muscle strength. The
      impact of IMT on clinical outcomes requires future confirmation.

PMID- 29584450
TI  - Corrigendum.

PMID- 29584452
TI  - Clinical-Community Collaboration: A Strategy to Improve Retention and Outcomes in
      Low-Income Minority Youth in Family-Based Obesity Treatment.
AB  - BACKGROUND: Clinical-community collaboration is a promising strategy for
      pediatric obesity treatment, but current research is limited. This study examined
      the effect of a family-based treatment program embedded in a primary care clinic
      on retention and changes in child weight status at 1 year. METHODS: Children (2
      16 years, BMI >=85th percentile, 87.0% Hispanic) and their parents were recruited
      from a single pediatric clinic for Healthy Hawks Primary Plus (HHP+). Children
      were referred by physicians and enrolled by a bilingual clinic-based recruitment
      coordinator. Participants received 12 weekly 2-hour sessions focused on lifestyle
      modification and health behavior change and then received bimonthly follow-up
      visits with their clinic-based physician through 1-year follow-up. Child body
      mass index (BMI) percentage of the 95th percentile (%BMIp95) was measured as the
      primary outcome at baseline, postintervention, and 1-year follow-up. Random
      effect multilevel models assessed changes in child weight status over time
      accounting for clustering by family. To further evaluate the impact, HHP+
      retention and changes in child weight status were compared to a standard 12-week
      treatment program only. RESULTS: HHP+ participants had significantly better
      retention at 1 year (73.9%, p <= 0.001) compared to the standard treatment
      program (38.3%). In HHP+, physician visit attendance was significantly correlated
      with retention at 1 year (r = 0.69, p <= 0.001), and HHP+ completers had
      significant reductions in %BMIp95 between baseline and 1-year follow-up (p =
      0.03). CONCLUSION: Clinical-community partnerships might be a promising strategy
      to improve retention and reduce child weight status in populations currently
      underrepresented in obesity treatment.

PMID- 29584451
TI  - Epithelial Heparan Sulfate Contributes to Alveolar Barrier Function and Is Shed
      during Lung Injury.
AB  - The lung epithelial glycocalyx is a carbohydrate-enriched layer lining the
      pulmonary epithelial surface. Although epithelial glycocalyx visualization has
      been reported, its composition and function remain unknown. Using
      immunofluorescence and mass spectrometry, we identified heparan sulfate (HS) and
      chondroitin sulfate within the lung epithelial glycocalyx. In vivo selective
      enzymatic degradation of epithelial HS, but not chondroitin sulfate, increased
      lung permeability. Using mass spectrometry and gel electrophoresis approaches to
      determine the fate of epithelial HS during lung injury, we detected shedding of
      20 saccharide-long or greater HS into BAL fluid in intratracheal LPS-treated
      mice. Furthermore, airspace HS in clinical samples from patients with acute
      respiratory distress syndrome correlated with indices of alveolar permeability,
      reflecting the clinical relevance of these findings. The length of HS shed during
      intratracheal LPS-induced injury (>=20 saccharides) suggests cleavage of the
      proteoglycan anchoring HS to the epithelial surface, rather than cleavage of HS
      itself. We used pharmacologic and transgenic animal approaches to determine that
      matrix metalloproteinases partially mediate HS shedding during intratracheal LPS
      induced lung injury. Although there was a trend toward decreased alveolar
      permeability after treatment with the matrix metalloproteinase inhibitor,
      doxycycline, this did not reach statistical significance. These studies suggest
      that epithelial HS contributes to the lung epithelial barrier and its degradation
      is sufficient to increase lung permeability. The partial reduction of HS shedding
      achieved with doxycycline is not sufficient to rescue epithelial barrier function
      during intratracheal LPS-induced lung injury; however, whether complete
      attenuation of HS shedding is sufficient to rescue epithelial barrier function
      remains unknown.

PMID- 29584454
TI  - Novel App- and Web-Supported Diabetes Prevention Program to Promote Weight
      Reduction, Physical Activity, and a Healthier Lifestyle: Observation of the
      Clinical Application.
AB  - BACKGROUND: The increasing incidence of type 2 diabetes mellitus presents as a
      tsunami of health problems and health care costs. Preventing this development
      needs to target the underlying rise in metabolic syndrome cases through obesity
      and unhealthy lifestyle. Obesity is frequently perceived as a social issue with
      implicit psychological strain; health apps/weight-reduction programs are
      mushrooming from this side. The present program intends to bring weight reduction
      into the hands of HCPs by utilizing advanced digital technology. METHODS: The
      prospective observational study analyzed 166 patients with metabolic syndrome as
      treated for weight reduction in 23 medical practices in Germany. Two approaches
      were observed: usual care (UC; n = 57) and a personalized health management
      program (PHM; n = 109). Key for PHM was the interaction between HCP and patient:
      reinforcing lifestyle changes through personalized goals and HCP-feedback via app
      and web-based communication. Comparing PHM/UC was based on a time-to-success (5%
      weight reduction) analysis by Cox regression. Further exploratory analyses
      addressed the comparison of achievers and nonachievers. RESULTS: Cox regression
      adjusted for sex, age, and BMI revealed a chance ratio for weight reduction of
      6.2 (2.4-16.2, p = .0003) favoring PHM. Expected success rates were 44.8% for
      PHM, 11.5% for UC. PHM achievers reduced their weight by 8.0% and lowered their
      BMI by 2.7 points. Motivation for lifestyle changes represented a key for
      success. CONCLUSIONS: The approach of enhanced interaction of HCPs and patients
      via app- and web-based communication was a clear success and delivered favorable
      responder rates. Treating obesity from a medical viewpoint will help to deepen
      the motivation for changing lifestyles. The study represents a cornerstone for a
      wider scoped application of these novel digital health approaches.

PMID- 29584455
TI  - Vestibular and oculomotor findings in neurologically-normal, non-concussed
      children.
AB  - OBJECTIVE: To determine the proportion of non-concussed, neurologically normal
      children with failures on a vestibular and oculomotor examination for concussion
      performed in an acute setting. DESIGN: This was a cross-sectional study of
      subjects 6-18 years old presenting to a paediatric emergency department with non
      neurologic chief complaints. The examination was administered by a paediatric
      emergency medicine physician, and includes assessments of dysmetria, nystagmus,
      smooth pursuits, saccades, gaze stability, near-point of convergence, and
      gait/balance testing. RESULTS: Of the 295 subjects enrolled, 24% failed at least
      one element of testing. About 13% had >1 failed element and 5% had >2 failed
      elements. About 29% of females and 19% of males had failed examinations. By age,
      15% of subjects 6-8 years old, 32% 9-11 years, 32% 12-14 years, and 26% 15-18
      years had failed examinations. Overall, 10% were unable to complete the exam due
      to developmental age. CONCLUSIONS: The provider should be aware that a proportion
      of non-concussed children may demonstrate failure on a single element of the
      vestibular and oculomotor exam. While this testing is of benefit to the acute
      care provider in diagnosing paediatric concussion, its utility is greatest in the
      context of an injury history with acute onset of concussion symptoms.

PMID- 29584453
TI  - Rural Residence and COPD Exacerbations: Analysis of the SPIROMICS Cohort.
AB  - RATIONALE: Rural residence is associated with poor outcomes in several chronic
      diseases. The association between rural residence and chronic obstructive
      pulmonary disease (COPD) exacerbations remains unclear. OBJECTIVE: To determine
      the independent association between rural residence and COPD-related outcomes
      including COPD exacerbations, airflow obstruction and symptom burden. METHODS: A
      total of 1684 Subpopulations and Intermediate Outcome Measures in COPD Study
      (SPIROMICS) participants with FEV1/FVC<0.70 had geocoding-defined rural-urban
      residence status determined (N=204 rural and N=1480 urban). Univariate and
      multivariate logistic and negative binomial regressions were performed to assess
      the independent association between rurality and COPD outcomes including
      exacerbations, lung function, and symptom burden. The primary exposure of
      interest was rural residence, determined by geocoding of home address to the
      block level at time of study enrollment. Additional covariates of interest
      included demographic and clinical characteristics, occupation, and occupational
      exposures.The primary outcome measures were exacerbations determined over the one
      year course after enrollment by quarterly telephone calls and at an annual
      research clinic visit. Odds ratio and incidence rate of exacerbations that
      required treatment with medications including steroids or antibiotics (total
      exacerbations), and exacerbations leading to hospitalization (severe
      exacerbations) were determined after adjusting for relevant covariates. RESULTS:
      Rural residence was independently associated with 70% increase in odds of total
      exacerbations [OR 1.70 (95% CI 1.13-2.56); p=0.012] and 46% higher incidence rate
      of total exacerbations [IRR 1.46 (95% CI 1.02-2.10); p=0.039]. There was no
      association between rural residence and severe exacerbations. Agricultural
      occupation was independently associated with increased odds and incidence of
      total and severe exacerbations. Inclusion of agricultural occupation to analysis
      attenuated the association between rural residence and odds and incidence rate of
      total exacerbations [OR 1.52 (95% CI 1.00-2.32; p=0.05) and IRR 1.39 (95% CI 0.97
      - 1.99); p=0.07]. There was no difference in symptoms or airflow obstruction
      between rural and urban participants. CONCLUSIONS: Rural residence is
      independently associated with increased odds and incidence of total, but not
      severe COPD exacerbations. These associations are not fully explained by
      agriculture-related exposures, highlighting the need for future research into
      potential mechanisms of increased risk of COPD exacerbations in the rural
      population.

PMID- 29584456
TI  - Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN
      Ovarian 200 Phase III study design.
AB  - Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in
      multiple solid tumors. Here, we describe the rationale and design for JAVELIN
      Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the
      role of checkpoint inhibition in women with ovarian cancer. This three-arm trial
      is comparing avelumab administered alone or in combination with pegylated
      liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients
      with platinum-resistant/refractory recurrent ovarian, fallopian tube or
      peritoneal cancer. Eligible patients are not preselected based on PD-L1
      expression and may have received up to three prior lines of chemotherapy for
      platinum-sensitive disease, but none for resistant disease. Overall survival and
      progression-free survival are primary end points, and secondary end points
      include biomarker evaluations and pharmacokinetics.

PMID- 29584457
TI  - Acupoint Massage for Managing Cognitive Alterations in Older Adults: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Cognitive disorders pose a major problem in the aging population
      across the globe. Acupoint massage has been used to improve cognitive functions
      in older adults. In this study, the authors performed a meta-analysis to evaluate
      the usefulness of acupoint massage in preventing cognitive declines in older
      adults. DESIGN: The authors searched for randomized controlled trials (RCTs)
      reporting on the effectiveness of acupoint massage on cognition in older adults
      in the following literature databases: PubMed, MEDLINE, Embase, CINAHL,
      ScienceDirect, Foreign Medical Journal Service, Cochrane Library, VIP
      Information, Chinese National Knowledge Infrastructure, WANFANG, and Chinese
      Biomedical. Two reviewers independently extracted the data related to the study
      and participants' characteristics and the cognitive impairment outcomes. Only
      RCTs meeting the inclusion criteria were used in the present meta-analysis.
      RESULTS: Eight RCTs with 657 participants in total (age >=60 years) were
      included. It is actually 8 for synthetic and 6 in the meta-analysis. The authors
      calculated the pooled estimates of the random effects of changes in the Mini
      Mental State Examination to compare the groups with and without acupoint massage.
      The merged mean difference (MD) was 1.94 (95% confidence interval, C.I., [1.41
      2.47], p < 0.00001) after 3 months of acupoint massage treatment and 3.04 (95%
      C.I. [2.43-3.64], p < 0.00001) after 6 months of treatment. They also calculated
      the merged MD of the Wechsler Memory Scale-Revised Chinese version after 6 months
      of acupoint massage. Visual Reproduction was 2.95 (95% C.I. [1.30-4.60], p =
      0.0005), Associate Learning was 1.89 (95% C.I. [1.41-2.37], p < 0.00001), Logical
      Memory was 2.85 (95% C.I. [2.06-3.63], p < 0.00001), and Digit Span was 3.16 (95%
      C.I. [2.59-3.73], p < 0.00001). The Cochrane Handbook for Systematic Reviews of
      Interventions was used to rate the quality of the studies, which was moderate
      overall. CONCLUSION: The findings suggested that acupoint massage is an effective
      intervention for maintaining cognitive functions in older adults.

PMID- 29584458
TI  - The effect of an L/N-type calcium channel blocker on intradialytic blood pressure
      in intradialytic hypertensive patients.
AB  - BACKGROUND: Intradialytic hypertension (HTN), which is one of the poor prognostic
      markers in patients undergoing hemodialysis, may be associated with sympathetic
      overactivity. The L/N-type calcium channel blocker, cilnidipine, has been
      reported to suppress sympathetic nerves activity in vivo. Therefore, we
      hypothesized that cilnidipine could attenuate intradialytic systolic blood
      pressure (SBP) elevation. METHODS: Fifty-one patients on chronic hemodialysis who
      had intradialytic-HTN (SBP elevation >=10 mmHg during hemodialysis) and no fluid
      overload were prospectively randomized into two groups: control and cilnidipine
      groups. Cilnidipine group patients took cilnidipine (10 mg/day) for 12 weeks. The
      primary endpoint was the change in the intradialytic SBP elevation before and
      after the 12-week intervention. RESULTS: Before the intervention, no differences
      were observed in age, sex or pre-dialytic SBP (148.5 +/- 12.9 vs. 148.3 +/- 19.3
      mmHg) between the two groups. Intradialytic SBP elevation was unchanged in the
      control group. Cilnidipine significantly lowered the post-dialytic SBP with an
      attenuation of the intradialytic SBP elevation from 12.0 +/- 15.4 mmHg to 4.8 +/-
      10.1 mmHg. However, the observed difference in the intradialytic SBP elevation by
      cilnidipine did not reach statistical significance (group*time interaction effect
      p = 0.25). Cathecolamine levels were unaffected by the intervention in both
      groups. CONCLUSION: Cilnidipine lowers both the pre- and post-dialytic SBP and
      might attenuate intradialytic SBP elevation. Therefore, cilnidipine may be
      effective in lowering SBP during HD in patients with intradialytic-HTN.

PMID- 29584459
TI  - Perimenstrual asthma: Report of a case with therapeutic intervention of oral
      prednisone.
AB  - INTRODUCTION: Many asthmatic women of childbearing age experience cyclical
      aggravation of asthmatic symptoms during the perimenstrual period, or
      perimenstrual asthma (PMA). PMA is considered to be a difficult-to-treat asthma
      phenotype; conventional asthma therapies are not always effective against PMA.
      CASE STUDY: We report a case of a 27-year-old female with PMA who had received
      standard asthma treatment since 2013. RESULT: The patient showed a dramatic
      response to therapeutic intervention of oral prednisone, taken for 7 days prior
      to menstruation each month, in a dose-dependent manner. CONCLUSION: Premenstrual
      treatment with oral prednisone may be a successful new direction for the
      treatment of PMA, a troublesome type of asthma.

PMID- 29584460
TI  - Strengthening One Health Through Investments in Agricultural Preparedness.
AB  - There are links among agriculture and zoonotic diseases, transboundary diseases
      in domesticated and wild animals, climate patterns, and human population
      migrations. A natural or intentionally occurring high-consequence infectious
      disease ("biothreat") often has no geographic boundaries and has the potential to
      result in disease epidemics in humans, animals, or both. Although significant
      strides have been made globally in preparing for a natural or intentional
      introduction of an emerging and/or zoonotic disease, much remains to be
      accomplished. Enhancing animal health and well-being is a vital component to
      enable a sustainable, safe, and nutritious food supply for global food economies.
      This article explores the biothreat environment, its One Health
      interrelationship, and the significance and role of US agriculture in One Health.
      We provide an overview of the US Emergency Medical Countermeasure Enterprise
      (EMCE) and current state of veterinary and zoonotic medical countermeasures
      portfolio management in the US government, veterinary biologic industry, not-for
      profit groups, and public-private partnerships. The highest zoonotic and
      epizootic threats to the US livestock industry are briefly reviewed, and
      currently available veterinary medical countermeasures are presented. Lastly,
      important gaps and priorities are identified, followed by specific
      recommendations to address these gaps.

PMID- 29584461
TI  - Case Studies in Exercise and Sport Sciences: A Powerful Tool to Bridge the
      Science-Practice Gap.
AB  - Despite the progress made by the scientific exercise community in collaborating
      and communicating with non-scientist coaches, there is room for improvement.
      Coaches find research difficult to understand, feel that their interests are not
      being addressed by exercise research, and rely on peer-discussion to further
      their coaching knowledge base while consuming little peer-reviewed articles. One
      useful strategy to bridge the science-practice gap is with case-studies. In
      addition to furthering our understanding of the physiology, psychology, and
      training schedules of elite athletes, case studies can serve 1) as a useful
      communication channel with coaches if presented as narratives and 2) to establish
      and strengthen relationships between scientists and coaches leading to fruitful
      research collaborations. The purpose of this invited commentary is to discuss
      these two less-recognized benefits of case-studies, and propose a way to
      incorporate case-studies more frequently alongside group-based studies.

PMID- 29584463
TI  - Do we still need cryoprecipitate? Cryoprecipitate and fibrinogen concentrate as
      treatments for major hemorrhage - how do they compare?
AB  - INTRODUCTION: Major hemorrhage is a source of significant mortality and morbidity
      worldwide. Identification and characterization of coagulation impairment
      associated with major hemorrhage has suggested a key role for fibrinogen
      deficiency, however the optimum mode of replacement of fibrinogen remains
      unclear, and standardized major hemorrhage protocols may overlook context
      dependent variations in individual patients' clotting derangement. Areas covered:
      This paper examines the current practice and evidence regarding the role of
      different modes of fibrinogen replacement in major hemorrhage in 3 distinct
      clinical settings: trauma, obstetric hemorrhage, and gastrointestinal hemorrhage
      with associated liver disease. A literature search was carried out electronically
      using Athens access to the National Health Service evidence health information
      resources, primarily PubMed and Google Scholar. Expert commentary: Two key
      questions need to be addressed. First, what is the role of concentrated
      fibrinogen (by comparison to no fibrinogen), and second, which concentrated
      source or product is more effective (or cost-effective)? Current practice and
      concept is derived largely from small pilot trials in the trauma setting, but
      results from larger studies are awaited. More comparative data on changes to
      clotting profiles in different groups of bleeding patients are needed to help
      delineate differences and guide interventional treatment studies.

PMID- 29584462
TI  - Effects of Caffeinated Gum on a Battery of Soccer-Specific Tests in Trained
      University-Standard Male Soccer Players.
AB  - The purpose of this study was to determine whether caffeinated gum influenced
      performance in a battery of soccer-specific tests used in the assessment of
      performance in soccer players. In a double-blind, randomized, crossover design,
      10 male university-standard soccer players (age: 19 +/- 1 years, stature: 1.80 +/
      0.10 m, body mass: 75.5 +/- 4.8 kg) masticated a caffeinated (200 mg; caffeine)
      or control (0 mg; placebo) gum on two separate occasions. After a standardized
      warm-up, gum was chewed for 5 min and subsequently expectorated 5 min before
      players performed a maximal countermovement jump, a 20-m sprint test, and the Yo
      Yo Intermittent Recovery Test Level 1. Performance on 20-m sprints was not
      different between trials (caffeine: 3.2 +/- 0.3 s, placebo: 3.1 +/- 0.3 s; p =
      .567; small effect size: d = 0.33), but caffeine did allow players to cover 2.0%
      more distance during Yo-Yo Intermittent Recovery Test Level 1 (caffeine: 1,754 +/
      156 m, placebo: 1,719 +/- 139 m; p = .016; small effect size: d = 0.24) and
      increase maximal countermovement jump height by 2.2% (caffeine: 47.1 +/- 3.4 cm,
      placebo: 46.1 +/- 3.2 cm; p = .008; small effect size: d = 0.30). Performance on
      selected physical tests (Yo-Yo Intermittent Recovery Test Level 1 and
      countermovement jump) was improved by the chewing of caffeinated gum in the
      immediate period before testing in university-standard soccer players, but the
      sizes of such effects were small. Such findings may have implications for the
      recommendations made to soccer players about to engage with subsequent exercise
      performance.

PMID- 29584464
TI  - Endophyte-enhanced phytoremediation of DDE-contaminated using Cucurbita pepo: A
      field trial.
AB  - Although the use of the pesticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane
      (DDT) was banned from the mid-1970s, its most abundant and recalcitrant
      degradation product, 2,2-bis(p-chlorophenyl)-1,1-dichloro-ethylene (DDE), is
      still present in terrestrial and aquatic ecosystems worldwide. Zucchini
      (Cucurbita pepo ssp. pepo) has been shown to accumulate high concentrations of
      DDE and was proposed for phytoremediation of contaminated soils. We performed a
      field trial covering a full plant life cycle. C. pepo plants inoculated with the
      plant growth-promoting endophytic strains Sphingomonas taxi UH1, Methylobacterium
      radiotolerans UH1, Enterobacter aerogenes UH1, or a consortium combining these 3
      strains were grown on a DDE-contaminated field for 100 days. The effects of these
      inoculations were examined at both the plant level, by evaluating plant weight
      and plant DDE-content, and at the level of the cultivable and total endophytic
      communities. Inoculating plants with S. taxi UH1, M. radiotolerans UH1, and the
      consortium increased plant weight. No significant effects of the inoculations
      were observed on DDE-concentrations in plant tissues. However, the amount of DDE
      accumulated by C. pepo plants per growing season was significantly higher for
      plants that were inoculated with the consortium of the 3 strains. Therefore,
      inoculation of C. pepo with DDE-degrading endophytes might be promising for
      phytoremediation applications.

PMID- 29584465
TI  - Electromagnetic field pretreatment of Sinapis alba seeds improved cadmium
      phytoextraction.
AB  - It was hypothesized that electromagnetic field (EMF) pretreatment of white
      mustard (Sinapis alba L.) seeds could increase the accumulation of non-essential,
      pollutant heavy metals such as cadmium (Cd) in shoots. Seeds of white mustard
      were treated with either 60 or 120 mT of alternating EMF (50 Hz) for 1 minute and
      then grown in a Petri dish in the presence of Cd, in comparison to the control
      (seeds grown without EMF pretreatment). Biomass production and content of calcium
      (Ca) and Cd in seedling shoots were measured. The Cd content in shoots from the
      EMF-treated seeds was higher in both variants than in the control (by 73% and
      78%, respectively; p < 0.05). In plants treated with 60 mT, the Ca content was
      slightly, but significantly, lower (3%) than in the control. EMF stimulation did
      not affect the biomass production. The results have shown potential benefits of
      this physical seed pretreatment method in the context of cadmium phytoextraction,
      but more research is needed.

PMID- 29584466
TI  - Characterization of coal fly ash and use of plants growing in ash pond for
      phytoremediation of metals from contaminated agricultural land.
AB  - Mobilization of heavy metals around coal power plants due to improper disposal of
      fly ash (FA) and wastewater have led to release of pollutants into the
      environment. For protection of inimitable natural resources, application of
      economical and effective technologies is needed such as phytoremediation is cost
      effective, ecofriendly and a better option for elimination of metal from
      contaminated sites. Twelve plant species were sampled from ash dyke of Singrauli
      and screened for accumulation of metals for this study. Mobilization ratio of
      metals from soil to plant was evaluated to determine translocation factor. CILLAS
      analyzer, Raman spectroscopy and SEM-EDX were used for characterization of
      particle size, functional groups and morphology of fly ash. Results showed mean
      metal concentrations in contaminated soil for Fe, Mn, Cr, Zn, Ni, Cu, Cd and Pb
      were 909.4, 60.6, 9.5, 134.8, 13.6, 26.7, 2.9 and 25.4 ug g-1 respectively.
      Enrichment factors for soil, root and shoot for a contaminated site were 1.9, 3.8
      & 4.3 for Zn and 2.7, 3.5 & 3.8 for Cd. Six hyper-accumulators with absorption
      efficiency >1 viz. I. carnea, S. nigrum, S. munja, T. angustifolia, C. dactylon
      and P. hysterophorus were identified which may be cultivated successively to
      reclaim and restore damaged agricultural land.

PMID- 29584467
TI  - Regression model, artificial neural network, and cost estimation for biosorption
      of Ni(II)-ions from aqueous solutions by Potamogeton pectinatus.
AB  - This study investigated the application of Potamogeton pectinatus for Ni(II)-ions
      biosorption from aqueous solutions. FTIR spectra showed that the functional
      groups of -OH, C-H, -C = O, and -COO- could form an organometallic complex with
      Ni(II)-ions on the biomaterial surface. SEM/EDX analysis indicated that the voids
      on the biosorbent surface were blocked due to Ni(II)-ions uptake via an ion
      exchange mechanism. For Ni(II)-ions of 50 mg/L, the adsorption efficiency
      recorded 63.4% at pH: 5, biosorbent dosage: 10 g/L, and particle-diameter: 0.125
      0.25 mm within 180 minutes. A quadratic model depicted that the plot of removal
      efficiency against pH or contact time caused quadratic-linear concave up curves,
      whereas the curve of initial Ni(II)-ions was quadratic-linear convex down.
      Artificial neural network with a structure of 5 - 6 - 1 was able to predict the
      adsorption efficiency (R2: 0.967). The relative importance of inputs was: initial
      Ni(II)-ions > pH > contact time > biosorbent dosage > particle-size. Freundlich
      isotherm described well the adsorption mechanism (R2: 0.974), which indicated a
      multilayer adsorption onto energetically heterogeneous surfaces. The net cost of
      using P. pectinatus for the removal of Ni(II)-ions (4.25 +/- 1.26 mg/L) from real
      industrial effluents within 30 minutes was 3.4 $USD/m3.

PMID- 29584468
TI  - 226Ra, 238U and Cd adsorption kinetics and binding capacity of two cyanobacterial
      strains isolated from highly radioactive springs and optimal conditions for
      maximal removal effects in contaminated water.
AB  - Biomass-based decontamination methods are among the most interesting water
      treatment techniques. In this study, 2 cyanobacterial strains, Nostoc punctiforme
      A.S/S4 and Chroococcidiopsis thermalis S.M/S9, isolated from hot springs
      containing high concentrations of radium (226Ra), were studied to be associated
      with removal of radionuclides (238U and 226Ra) and heavy metal cadmium (Cd) from
      aqueous solutions. The adsorption equilibrium data was described by Langmuir and
      Freundlich isotherm models. Kinetic studies indicated that the sorption of 3
      metals followed pseudo-second-order kinetics. Effects of biomass concentration,
      pH, contact time, and initial metal concentration on adsorption were also
      investigated. Fourier-transform infrared spectroscopy revealed active binding
      sites on the cyanobacterial biomass. The obtained maximum biosorption capacities
      were 630 mg g-1 and 37 kBq g-1 for 238U and 226Ra for N. punctiforme and 730 mg g
      1 and 55 kBq g-1 for C. thermalis. These 2 strains showed maximum binding
      capacity 160 and 225 mg g-1, respectively for Cd adsorption. These results
      suggest that radioactivity resistant cyanobacteria could be employed as an
      efficient adsorbent for decontamination of multi-component, radioactive and
      industrial wastewater.

PMID- 29584469
TI  - Profiling of plants at petroleum contaminated site for phytoremediation.
AB  - The paucity of information in the literature on the characteristics of plants
      that could be used for phytoremediation of petroleum hydrocarbons (PHC)
      contaminated sites was the principal reason for this study. The aim of the study
      was to identify indigenous plants growing in PHC-impacted soil in Umuahia in
      eastern-Nigeria that have the ability to phytoremediate soils contaminated with
      hydrocarbons under tropical monsoon climate conditions. A total of 28 native
      plant species from different families growing in and around hydrocarbon-impacted
      soil in the vicinity of vandalized pipelines carrying petroleum products were
      collected and studied for their ability to grow in a hydrocarbon-impacted soil
      and remove the PHC from the impacted soil. Some of the plants demonstrated the
      ability to grow in soil with high levels of the total petroleum hydrocarbons
      (TPH), which shows that they may be tolerant to hydrocarbons in soil and could
      potentially phytoremediate a hydrocarbon-contaminated soil. Chromolaena odorata,
      Aspilia africana, Chloris barbata, Pasparlum vaginatum, Bryophyllum pinnatum,
      Paspalum scrobiculatum, Cosmos bipinnatus, Eragrostis atrovirens, Cyperus
      rotundus, and Uvaria chamae showed tendencies to phytoremediate contaminated
      soil. By using bioaccumulation coefficient (BAC) as a measure of
      phytoremediation, results showed that C. odorata, A. africana, and U. chamae
      demonstrated the highest potentials to phytodegrade hydrocarbons in soil.

PMID- 29584470
TI  - A natural macroalgae consortium for biosorption of copper from aqueous solution:
      Optimization, modeling and design studies.
AB  - In this study, the capacity of a natural macroalgae consortium consisting of
      Chaetomorpha sp., Polysiphonia sp., Ulva sp. and Cystoseira sp. species for the
      removal of copper ions from aqueous environment was investigated at different
      operating conditions, such as solution pH, copper ion concentration and contact
      time. These environmental parameters affecting the biosorption process were
      optimized on the basis of batch experiments. The experimentally obtained data for
      the biosorption of copper ions onto the macroalgae-based biosorbent were modeled
      using the isotherm models of Freundlich, Langmuir, Sips and Dubinin-Radushkevich
      and the kinetic models of pseudo-first-order, pseudo-second-order, Elovich and
      Weber and Morris. The pseudo-first-order and Sips equations were the most
      suitable models to describe the copper biosorption from aqueous solution. The
      thermodynamic data revealed the feasibility, spontaneity and physical nature of
      biosorption process. Based on the data of Sips isotherm model, the biosorption
      capacity of biosorbent for copper ions was calculated as 105.370 mg g-1 under the
      optimum operating conditions. A single-stage batch biosorption system was
      developed to predict the real-scale-based copper removal performance of
      biosorbent. The results of this investigation showed the potential utility of
      macroalgae consortium for the biosorption of copper ions from aqueous medium.

PMID- 29584471
TI  - Adsorption of Cd(II) by rhizosphere and non-rhizosphere soil originating from
      mulberry field under laboratory condition.
AB  - In this study, the adsorption behavior of Cd ions by rhizosphere soil (RS) and
      non-rhizosphere soil (NS) originated from mulberry field was investigated. The
      Langmuir, Freundlich and the Dubinin-Radushkevich (D-R) equations were used to
      evaluate the type and efficiency of Cd adsorption. The RS was characterized by
      lower pH but the higher content of soil organic matter and cation exchange
      capacity (CEC) as compared to NS. Also, the maximum adsorption of Cd2+ for RS
      (5.87 mg/g) was slightly bigger than that for NS (5.36 mg/g). In Freundlich
      isotherm, the Kf of the adsorption of Cd2+ to surface of the RS components was
      higher than that of the NS, indicating stronger attraction between Cd2+ and
      components of the RS. According to the D-R model, the adsorption of Cd2+ by both
      soils was dominated by ion exchange phenomena. These results indicated that
      mulberry roots modified physical and chemical properties of the RS under field
      conditions, which also affected the Cd sorption efficiency by soil components
      during laboratory experiments. Current knowledge of the Cd2+ sorption processes
      in the rhizosphere of mulberry may be important if these trees are planted for
      use in phytoremediation of Cd contaminated soils.

PMID- 29584472
TI  - Physiological and molecular responses of pearl millet seedling to atrazine
      stress.
AB  - Pearl millet has been recommended beneficial for several therapeutic purposes.
      However, little is known of the physiological responses to abiotic stressors,
      especially of atrazine. In order to elucidate the physiological and molecular
      responses of pearl millet to atrazine stress, we studied the response of various
      biomarkers under increasing herbicide concentrations (0, 5, 10, and 50 mg/kg). We
      also quantified the levels of malondialdehyde (MDA) and reactive oxygen species
      (ROS) (H2O2 and O2*-) produced in the leaves to evaluate the extent of oxidative
      damage. Increasing atrazine concentrations significantly increased ROS and MDA
      production in the plant leaves. Ascorbate peroxidase (APX) and peroxidase (POD)
      activities increased, while catalase (CAT) and superoxide dismutase activities
      reduced with increasing atrazine concentrations. Generally, atrazine applied at
      50 mg/kg suppressed chlorophyll contents, whereas, chlorophyll (a/b) ratio was
      increased. Atrazine applied at 50 mg/kg significantly suppressed antioxidant gene
      expressions to the lowest. The APX gene showed overall low response to the
      atrazine treatments. The chloroplastic psbA gene showed highest expression with
      10 mg/kg atrazine, whereas atrazine at 50 mg/kg significantly suppressed the gene
      expression to its lowest. Pearl millet was able to suppress oxidative stress
      under low atrazine levels, but high atrazine concentration could induce more
      oxidative damage.

PMID- 29584473
TI  - Analysis of near crashes among teen, young adult, and experienced adult drivers
      using the SHRP2 naturalistic driving study.
AB  - OBJECTIVE: Motor vehicle crashes are the leading cause of death among young
      drivers. Though previous research has focused on crash events, near crashes offer
      additional data to help identify driver errors that could potentially lead to
      crashes as well as evasive maneuvers used to avoid them. The Strategic Highway
      Research Program 2 (SHRP2) Naturalistic Driving Study (NDS) contains extensive
      data on real-world driving and offers a reliable methodology to quantify and
      study near crashes. This article presents findings on near crashes and how they
      compare to crash events among teen, young adult, and experienced adult drivers.
      METHODS: A subset from the SHRP2 database consisting of 1,653 near crashes for
      teen (16-19 years, n = 550), young adult (20-24 years, n = 748), and experienced
      adult (35-54 years, n = 591) drivers was used. Onboard instrumentation including
      scene cameras, accelerometers, and Global Positioning System logged time series
      data at 10 Hz. Scene videos were reviewed for all events to classify near crashes
      based on 7 types: rear-end, road departure, intersection, head-on, side-swipe,
      pedestrian/cyclist, and animal. Near crash rates, incident type, secondary tasks,
      and evasive maneuvers were compared across age groups and between crashes and
      near crashes. For rear-end near crashes, vehicle dynamic variables including near
      crash severity, headway distance, time headway, and time to collision at the time
      of braking were compared across age groups. Crashes and near crashes were
      combined to compare the frequency of critical events across age. RESULTS: Teen
      drivers exhibited a significantly higher (P <.01) near crash rate than young
      adult and experienced adult drivers. The near crash rates were 81.6, 56.6, and
      37.3 near crashes per million miles for teens, young adults, and experienced
      adults, respectively. Teens were also involved in significantly more rear-end (P
      <.01), road departure (P <.01), side-swipe (P <.01), and animal (P <.05) near
      crashes compared to young and experienced adults. Teens exhibited a significantly
      greater (P <.01) critical event rate of 102.2 critical events per million miles
      compared to 72.4 and 40.0 critical events per million miles for young adults and
      experienced adults, respectively; the critical event rate ratio was 2.6 and 1.8
      for teens and young adults, respectively. CONCLUSIONS: To our knowledge, this is
      the first study to examine near crashes among teen, young adult, and experienced
      adult drivers using SHRP2 naturalistic data. Near crash and critical event rates
      significantly decreased with increasing age and driver experience. Overall, teens
      were more than twice as likely to be involved in critical events compared to
      experienced adults. These data can be used to develop more targeted driver
      training programs and help manufacturers design active safety systems based on
      the most common driving errors for vulnerable road users.

PMID- 29584474
TI  - The extent of backover collisions internationally.
AB  - This study reports good consistency in international comparisons of the number
      and severity of backover crashes. More than half occurred to pedestrians aged 60
      years and older. Children less than 9 years comprised 5% of these crashes with a
      similar percent aged 10 to 19 years. A significant 41% reduction in real-world
      backover crashes was found for Australian vehicles with reversing cameras. A
      range of driver and pedestrian maneuvers was found and 11 crash scenarios were
      identified in backover collisions. Mandating the fitting of reversing cameras to
      all vehicles and enhancements would likely enhance the safety of pedestrians in
      reversing maneuvers.

PMID- 29584475
TI  - Occupant kinematics of the Hybrid III, THOR-M, and postmortem human surrogates
      under various restraint conditions in full-scale frontal sled tests.
AB  - OBJECTIVE: The objective of this research was to compare the occupant kinematics
      of the Hybrid III (HIII), THOR-M, and postmortem human surrogates (PMHS) during
      full-scale frontal sled tests under 3 safety restraint conditions: knee bolster
      (KB), knee bolster and steering wheel airbag (KB/SWAB), and knee bolster airbag
      and steering wheel airbag (KBAB/SWAB). METHODS: A total of 20 frontal sled tests
      were performed with at least 2 tests performed per restraint condition per
      surrogate. The tests were designed to match the 2012 Toyota Camry New Car
      Assessment Program (NCAP) full-scale crash test. Rigid polyurethane foam
      surrogates with compressive strength ratings of 65 and 19 psi were used to
      simulate the KB and KBAB, respectively. The excursions of the head, shoulders,
      hips, knees, and ankles were collected using motion capture. Linear acceleration
      and angular velocity data were also collected from the head, thorax, and pelvis
      of each surrogate. Time histories were compared between surrogates and restraint
      conditions using ISO/TS 18571. RESULTS: All surrogates showed some degree of
      sensitivity to changes in restraint condition. For example, the use of a KBAB
      decreased the pelvis accelerations and the forward excursions of the knees and
      hips for all surrogates. However, these trends were not observed for the thorax,
      shoulders, and head, which showed more sensitivity to the presence of a SWAB. The
      average scores computed using ISO/TS 18571 for the HIII/PMHS and THOR-M/PMHS
      comparisons were 0.527 and 0.518, respectively. The HIII had slightly higher
      scores than the THOR-M for the excursions (HIII average = 0.574; THOR average =
      0.520). However, the THOR-M had slightly higher scores for the accelerations and
      angular rates (HIII average = 0.471; THOR average = 0.516). CONCLUSIONS: The data
      from the current study showed that both KBABs and SWABs affected the kinematics
      of all surrogates during frontal sled tests. The results of the objective rating
      analysis indicated that the HIII and THOR-M had comparable overall biofidelity
      scores. The THOR-M slightly outperformed the HIII for the acceleration and
      angular velocity data. However, the HIII scored slightly better than the THOR-M
      for the excursion data. The most notable difference in biofidelity was for the
      knee excursions, where the HIII had a much higher average ISO score. Only the
      biofidelity of the HIII and THOR-M with regard to occupant kinematics was
      evaluated in this study; therefore, future work will evaluate the biofidelity of
      the ATDs in terms of lower extremity loading, thoracic response, and neck
      loading.

PMID- 29584476
TI  - Advanced driver assistance systems for teen drivers: Teen and parent impressions,
      perceived need, and intervention preferences.
AB  - OBJECTIVE: From the advent of airbags to electronic stability control,
      technological advances introduced into automobile design have significantly
      reduced injury and death from motor vehicle crashes. These advances are
      especially pertinent among teen drivers, a population whose leading cause of
      death is motor vehicle crashes. Recently developed advanced driver assistance
      systems (ADAS) have the potential to compensate for skill deficits and reduce
      overall crash risk. Yet, ADAS is only effective if drivers are willing to use it.
      Limited research has been conducted on the suitability of ADAS for teen drivers.
      The goal of this study is to identify teen drivers' perceived need for ADAS,
      receptiveness to in-vehicle technology, and intervention preferences. The long
      term goal is to understand public perceptions and barriers to ADAS use and to
      help determine how these systems must evolve to meet the needs of the riskiest
      driving populations. METHODS: Three focus groups (N = 24) were conducted with
      licensed teen drivers aged 16-19 years and 2 focus groups with parents of teen
      drivers (N = 12). Discussion topics included views on how ADAS might influence
      driving skills and behaviors; trust in technology; and data privacy. Discussions
      were transcribed; the team used conventional content analysis and open coding
      methods to identify 12 coding domains and code transcripts with NVivo 10.
      Interrater reliability testing showed moderate to high kappa scores. RESULTS:
      Overall, participants recognized potential benefits of ADAS, including improved
      safety and crash reduction. Teens suggested that ADAS is still developing and
      therefore has potential to malfunction. Many teens reported a greater trust in
      their own driving ability over vehicle technology. They expressed that novice
      drivers should learn to drive on non-ADAS-equipped cars and that ADAS should be
      considered a supplemental aid. Many teens felt that overreliance on ADAS may
      increase distracted driving or risky behaviors among teens. Parents also
      expressed skepticism for the technology but felt that it would likely be a useful
      support for teen drivers after the initial learning phase. CONCLUSIONS: This
      study elicited important end-user viewpoints by exploring the intersection
      between advanced automobile safety technology and human perception for the
      particular use case of teen drivers. For example, despite evidence that teens are
      the highest risk driving population, teens trust their own driving skills and
      competence more than in-vehicle technology. This understanding will ultimately
      advance the safety of teen drivers by identifying barriers to effective ADAS use.

PMID- 29584477
TI  - Failed rib region prediction in a human body model during crash events with
      precrash braking.
AB  - OBJECTIVE: The objective of this study is 2-fold. We used a validated human body
      finite element model to study the predicted chest injury (focusing on rib
      fracture as a function of element strain) based on varying levels of simulated
      precrash braking. Furthermore, we compare deterministic and probabilistic methods
      of rib injury prediction in the computational model. METHODS: The Global Human
      Body Models Consortium (GHBMC) M50-O model was gravity settled in the driver
      position of a generic interior equipped with an advanced 3-point belt and airbag.
      Twelve cases were investigated with permutations for failure, precrash braking
      system, and crash severity. The severities used were median (17 kph), severe (34
      kph), and New Car Assessment Program (NCAP; 56.4 kph). Cases with failure enabled
      removed rib cortical bone elements once 1.8% effective plastic strain was
      exceeded. Alternatively, a probabilistic framework found in the literature was
      used to predict rib failure. Both the probabilistic and deterministic methods
      take into consideration location (anterior, lateral, and posterior). The
      deterministic method is based on a rubric that defines failed rib regions
      dependent on a threshold for contiguous failed elements. The probabilistic method
      depends on age-based strain and failure functions. RESULTS: Kinematics between
      both methods were similar (peak max deviation: DeltaXhead = 17 mm; DeltaZhead = 4
      mm; DeltaXthorax = 5 mm; DeltaZthorax = 1 mm). Seat belt forces at the time of
      probabilistic failed region initiation were lower than those at deterministic
      failed region initiation. The probabilistic method for rib fracture predicted
      more failed regions in the rib (an analog for fracture) than the deterministic
      method in all but 1 case where they were equal. The failed region patterns
      between models are similar; however, there are differences that arise due to
      stress reduced from element elimination that cause probabilistic failed regions
      to continue to rise after no deterministic failed region would be predicted.
      CONCLUSIONS: Both the probabilistic and deterministic methods indicate similar
      trends with regards to the effect of precrash braking; however, there are
      tradeoffs. The deterministic failed region method is more spatially sensitive to
      failure and is more sensitive to belt loads. The probabilistic failed region
      method allows for increased capability in postprocessing with respect to age. The
      probabilistic failed region method predicted more failed regions than the
      deterministic failed region method due to force distribution differences.

PMID- 29584478
TI  - Driving style indicator using UDRIVE NDS data.
AB  - OBJECTIVE: In order to analyze specific events while driving (such as a safety
      critical event [SCE] or secondary task), we were interested in studying whether
      driving behavior was unusual around the event. An indicator characterizing
      driving style (driving style indicator [DSI]) was estimated for each driver by
      using naturalistic data. The analysis of the gap in driving style could be
      calculated for a specific trip or even a time window and could help characterize
      events: a more risky situation when DSI was above average, increase in safety
      margins when under average. METHODS: Lateral acceleration and longitudinal
      acceleration were used for DSI calculation. The first step consisted in filtering
      the signal acquired by the inertial measurement unit (60 Hz). The noise was
      filtered out with an eighth order, phase-compensated digital low-pass Butterworth
      filter with a cut-out frequency of 5 Hz and offsets were compensated for. The
      second step consisted in calculating the jerk of the acceleration in lateral and
      longitudinal directions for each trip. The third step summarized the distribution
      of these jerks for all trips of each driver. Finally, the DSI was defined as the
      standard deviation of this distribution. A driver was represented by lateral DSI
      and longitudinal DSI. RESULTS: The indicator was used on French pilot data (10
      drivers) and on UK data (30 drivers) from the UDRIVE project. To assess this
      indicator, tests on track were conducted by professional drivers simulating two
      opposite driving style. The first results were promising and discriminated a
      smooth from a rough driving style. Indeed, in the pilot data, the classification
      was in accordance with our expectations and confirmed by videos. The same kind of
      distribution was observed in the UK data and needs to be confirmed when the
      UDRIVE database is complete. CONCLUSION: DSI is a new parameter that will be used
      to define clusters of drivers and study variation of driving parameters in each
      class during selected events (SCE, secondary task, etc.) in the UDRIVE project.

PMID- 29584479
TI  - Injury risk functions based on population-based finite element model responses:
      Application to femurs under dynamic three-point bending.
AB  - OBJECTIVE: The goal of this study was to explore a framework for developing
      injury risk functions (IRFs) in a bottom-up approach based on responses of
      parametrically variable finite element (FE) models representing exemplar
      populations. METHODS: First, a parametric femur modeling tool was developed and
      validated using a subject-specific (SS)-FE modeling approach. Second, principal
      component analysis and regression were used to identify parametric geometric
      descriptors of the human femur and the distribution of those factors for 3 target
      occupant sizes (5th, 50th, and 95th percentile males). Third, distributions of
      material parameters of cortical bone were obtained from the literature for 3
      target occupant ages (25, 50, and 75 years) using regression analysis. A Monte
      Carlo method was then implemented to generate populations of FE models of the
      femur for target occupants, using a parametric femur modeling tool. Simulations
      were conducted with each of these models under 3-point dynamic bending. Finally,
      model-based IRFs were developed using logistic regression analysis, based on the
      moment at fracture observed in the FE simulation. In total, 100 femur FE models
      incorporating the variation in the population of interest were generated, and
      500,000 moments at fracture were observed (applying 5,000 ultimate strains for
      each synthesized 100 femur FE models) for each target occupant characteristics.
      RESULTS: Using the proposed framework on this study, the model-based IRFs for 3
      target male occupant sizes (5th, 50th, and 95th percentiles) and ages (25, 50,
      and 75 years) were developed. The model-based IRF was located in the 95%
      confidence interval of the test-based IRF for the range of 15 to 70% injury
      risks. The 95% confidence interval of the developed IRF was almost in line with
      the mean curve due to a large number of data points. CONCLUSIONS: The framework
      proposed in this study would be beneficial for developing the IRFs in a bottom-up
      manner, whose range of variabilities is informed by the population-based FE model
      responses. Specifically, this method mitigates the uncertainties in applying
      empirical scaling and may improve IRF fidelity when a limited number of
      experimental specimens are available.

PMID- 29584480
TI  - Kinematics and shoulder belt engagement of children on belt-positioning boosters
      during evasive steering maneuvers.
AB  - OBJECTIVE: To increase the protection of child passengers in crashes preceded by
      evasive steering, understanding of how children interact with the seat belt in
      such situations is essential. This study aims to quantify child kinematics and
      describe child-to-restraint interaction during evasive steering maneuvers.
      METHODS: Eighteen child volunteers (aged 5-10) were seated on the rear seat of a
      passenger vehicle. A professional driver made repeatable sharp turns at 50 km/h.
      Children were restrained by the seat belt on a booster cushion (BC) and on an
      integrated booster cushion (IBC). Kinematics of the nasion and upper sternum were
      analyzed with video tracking software and shoulder belt (SB) engagement and
      position were evaluated. RESULTS: Children moved laterally inboard, and SB-to
      body interaction was influenced by booster and stature. Shorter children
      displayed initial SB positions closer to the neck with less instances of gap
      between the SB and the lower torso, resulting in more curved belt paths on the
      IBC. On the BC, shorter children had less of the SB in contact with the torso and
      straight belt paths were observed throughout steering. Taller children generally
      had the SB initially mid-shoulder with less instances of gap, resulting in curved
      belt paths at initial and maximum displacements on both boosters. Children loaded
      the shoulder belt by axially rotating their torso into the SB more often on the
      IBC compared to BC. The SB generally stayed on the shoulder, with 89% of slip-off
      instances occurring for shorter children on the BC. Shorter children on the BC
      had the largest average inboard nasion displacement (120 mm). Taller children on
      the BC had the lowest average inboard displacement of the nasion (100 mm). All
      children initially displaced on average 90 mm inboard with their upper sternum.
      CONCLUSIONS: Initial SB position on the shoulder and torso differed with booster
      and stature, which influenced how children engaged with the seat belt during
      steering. Children with less SB initially in contact with the torso moved
      laterally behind the belt, resulting in straighter SB paths and outboard motion
      of the SB on the shoulder (often ending far out or slipped off). When more of the
      SB was initially in contact with the torso, children tended to engage the SB
      more, moving with the belt and causing the SB path to become more curved,
      resulting in less inboard head displacement and less outboard motion of the SB on
      the shoulder. Enhanced understanding of how evasive steering affects the
      kinematic response of children provides valuable data for protection of children
      in real-world situations.

PMID- 29584481
TI  - The effectiveness of child restraint and seat belt legislation in reducing child
      injuries: The case of Serbia.
AB  - OBJECTIVE: The objective of this study is to determine the short- and long-term
      impacts of Serbia's 2009 update of child restraint and seat belt legislation on
      the incidence of pediatric motor vehicle-related injury. With this new law, the
      use of child restraints in children age 0-3 became mandatory, and children 4-12
      had to wear seat belts in the rear seats. METHODS: A unique data set with
      assembled information from public institutions of the Republic of Serbia from
      January 2004 to December 2014 and analyses based on interrupted time series were
      carried out. Eight outcome variables were assessed: monthly rate of injured
      children for 2 age groups 0-3 and 4-12 per child population, number of registered
      motor vehicles, number of passengers transported, and number of passengers'
      kilometers traveled. Independent variables were short- and long-term impacts of
      Serbia's legislation update (June 2009). Data on injuries were obtained from
      Serbia's Road Traffic Safety Agency. Child population and other transport-related
      data were obtained from the Statistical Office of the Republic of Serbia. We
      excluded fatalities from the analysis. RESULTS: In the first year of the updated
      legislation there was a reduction of 2.0% (confidence interval [CI], 0.1; 3.9) of
      injured children aged 0-3 and a reduction of 2.5% (CI, 0.6; 4.3) of injured
      children aged 4-12. Six years after enactment of the legislation, a significant
      reduction of 8.2% (CI, 3.5; 13.0) of injured children aged 4-12 was observed, but
      a nonsignificant reduction of 1.1% (CI, -5.8; 3.5) was found for injured children
      aged 0-3. By December 2014, 369 (CI, 186; 555) injuries among children aged 4-12
      were avoided. CONCLUSIONS: The case of Serbia suggests that the new law was
      effective in reducing injuries among children aged 0-3 in the short term and
      injuries among children aged 4-12 in both the short term and long term. To
      understand these results, we suggest 2 hypotheses. First, low proper usage of
      child restraint and weak police enforcement were likely to explain the short-term
      effect among children aged 0-3. Second, access to seat belts in rear seats was
      probably a condition that facilitated the use of these devices among children
      aged 4-12, protecting them during the period of the study.

PMID- 29584482
TI  - An evaluation of the real-world safety effect of a lane change driver support
      system and characteristics of lane change crashes based on insurance claims data.
AB  - OBJECTIVE: Lane changes, which frequently occur when vehicles travel on major
      roads, may contribute to critical situations that significantly affect the
      traffic flow and traffic safety. Thus, knowledge of lane change situations is
      important for infrastructure improvements as well as for driver support systems
      and automated driving development projects. The objectives of this study were to
      evaluate the crash avoidance performance of a lane change driver support system,
      the Blind Spot Information System (BLIS) in Volvo car models, and to describe the
      characteristics of lane change crashes by analyzing detailed information from
      insurance claim reports. METHODS: An overall evaluation of the safety effect of
      BLIS was performed by analyzing crash rate differences in lane change situations
      for cars with and without the optionally mounted BLIS system based on a
      population of 380,000 insured vehicle years. Further, crashes in which the repair
      cost of the host vehicle exceeded approximately US$1,250 were selected and
      compared. Finally, the study examined different precrash factors and crash
      configurations, using in-depth insurance claims data from representative lane
      change crash cases including all severity levels in a population of more than
      200,000 insured vehicle years. RESULTS: The technology did not significantly
      reduce the overall number of crashes when all types of lane change crashes and
      severity levels were considered, though a significant crash-reducing effect of
      31% for BLIS cars was found when more severe crashes with a repair cost exceeding
      US$1,250 were analysed. Cars with the BLIS technology also have a 30% lower claim
      cost on average for reported lane change crashes, indicating reduced crash
      severity. When stratifying the data into specific situations, by collecting
      precrash information in a case-by-case study, the influence of BLIS was indicated
      to differ for the evaluated situations, although no significant results were
      found. For example, during general lane change maneuvers (i.e., not while exiting
      or entering highways or during weaving/merging situations) the crash rate was
      reduced by 14%, whereas in weaving/merging situations the crash rate increased.
      CONCLUSIONS: The insurance data analyzed provided useful information about real
      world lane change crash characteristics by covering collisions in all crash
      severities and thus revealed information beyond what is available in, for
      example, data sets of police-reported crashes. This will guide further
      development of driver support systems. For crashes with repair cost exceeding
      US$1,250, a significant crash reduction was found, although the technology did
      not significantly reduce the total number of lane change crashes. An average
      lower insurance claim cost for cars equipped with the BLIS technology also
      indicated that the technology contributes to reduced crash severity even if
      crashes were not totally avoided. Stratifying the data into different lane change
      crash situations gave indications of the condition-specific performance of the
      system, even if the results were not statistically significant at the 95% level.

PMID- 29584483
TI  - Injury analysis of patients according to impact patterns involved in pedestrian
      traffic crashes.
AB  - OBJECTIVES: In cases of car-to-person pedestrian traffic crashes (PTCs), the
      principal issue is determining at what point the car collided with the
      pedestrian. Accordingly, the objective of the present study was to use the
      medical records of patients injured in PTCs to investigate the characteristics of
      crash types and the areas and injury severity and to determine whether there are
      differences in injuries due to the angle, motion, and position at the point of
      impact. METHODS: The present study examined 231 PTC patients admitted to the
      emergency room (ER) between January and December 2014. Electronic medical records
      from the hospital were used to divide the patient data according to Abbreviated
      Injury Scale (AIS) codes for injured areas based on sex, age, time of the crash,
      outcomes after ER treatment, and major symptoms. Among 231 patients, police
      reports on 67 crash cases, involving 70 people, were obtained with the help of
      local police departments, and these reports were used to reconstruct details of
      the actual crash. For statistical analysis, a chi-square test and a one-way
      analysis of variance calculation were used to compare the Injury Severity Score
      (ISS) based on groups and stages, with a statistical significance level set to P
      < .05. RESULTS: With respect to patients who were admitted for PTC, 52.4% were
      females and 47.6% were males. The frequency of crashes was high in middle-aged
      and elderly groups, as well as for youths between 10 and 19 years old. With
      respect to outcomes after ER treatment, discharge to home after symptom
      improvement was the most common outcome (24.6%). Admissions to the intensive care
      unit (25.1%) and to the general ward (23.8%) were also high. In terms of major
      symptoms, the most common injuries were to the head, resulting from a rotatory
      motion post impact (35.9%), and injuries to the legs, resulting from the impact
      of a direct collision with an object (25.1%). CONCLUSIONS: This study
      demonstrated that injuries to the chest and abdomen were the most severe in the
      fender vault group and head and neck injuries were the most severe in the roof
      vault group. In particular, the Injury Severity Score was highest in the roof
      vault group.

PMID- 29584484
TI  - Cyclist exposure to the risk of car door collisions in mixed function activity
      centers: A study in Melbourne, Australia.
AB  - OBJECTIVE: The objective of this study is to describe key risks related to
      dooring collisions on roads in mixed function activity centers by examining video
      footage recorded onboard the bicycles of cyclists riding through this road
      environment. The study aims to enhance our understanding of the risk associated
      with cyclist door collisions on these roads and to provide a focus for future
      studies that aim to identify measures that enhance cyclist safety. METHOD: The
      study measured 4 key risk exposures (per hour and kilometer), namely, on-street
      parked cars and 3 conditions associated with parked cars being accessed or
      egressed: door opened (a) after the cyclist passes (give-way event); (b) in the
      path of the cyclist without collision (obstruction event); and (c) in the path of
      the cyclist with collision (collision event). Exposure to the risk factors was
      measured using video footage recorded onboard the bicycles of adult cyclists (n =
      25) as they rode through this road environment. The average speed of cyclists was
      also estimated from these video data and related to the measures of exposure.
      RESULTS: The cycling experiences of the participants were observed over 3 h 58
      min and 84.0 km. On average, the sample was exposed to 1,166 parked car events
      per hour (55 per kilometer), 6.9 give-way events per hour (0.3 per kilometer),
      2.3 obstruction events per hour (0.1 per kilometer), and no collision events.
      There were 9 instances of obstruction events. In most cases, the cyclist was
      clearly visible (n = 7; 77.8%) and modified his or her position to avoid the door
      (n = 8; 88.9%). Moreover, the door was opened by the driver in nearly all cases
      (n = 8; 88.9%), primarily to exit the vehicle (n = 4; 44.4%) or enter the vehicle
      (n = 3; 33.3%). The average speed of cyclists was 22.7 km/h (SD = 4.1 km/h), and
      average speed tended to reduce as exposure to parked car events increased.
      CONCLUSION: Cyclists seldom interact with a vehicle occupant accessing or
      egressing a parked car, yet a concerning proportion of these interactions involve
      the occupant opening the door in the path of the cyclist, rather than waiting for
      the cyclist to pass. This suggests that there is still considerable need to
      identify measures that increase the likelihood that a vehicle occupant will look
      for cyclists before opening the car door, particularly in road environments where
      longer-term solutions such as physical separation are not readily achieved.

PMID- 29584485
TI  - Evaluation of a combination of community initiatives to reduce driving while
      intoxicated and other alcohol-related harms.
AB  - OBJECTIVES: In 2013, the community of Redlands, California, created an initiative
      using evidence-based strategies to deter driving under the influence (DUI),
      underage drinking and driving, public intoxication, and alcohol-related calls for
      service. The initiative, called "Responsible Redlands," included adopting a
      social host and a deemed approved local ordinance, using minor-decoy and shoulder
      tap operations, increasing sobriety checkpoints and saturation patrols,
      conducting responsible beverage service (RBS) training, using identification (ID)
      scanners to spot false IDs, and a publicity campaign to urge neighbors to report
      loud drinking parties. The objectives of this study were to determine whether the
      initiatives were carried out as planned and to assess any impacts that may have
      occurred due to the combination of initiatives. METHODS: Data from the Redlands
      Police Department were used to assess the process evaluation. The Statistical
      Analysis System (SAS) was used to create contingency tables to compare before
      (2007-2012) and after (2013-2014) the intervention start date and to conduct time
      series analyses and calculate chi-squared test statistics on five outcome
      measures: DUI arrests, underage drinking violations, public intoxication
      violations, alcohol calls for service, and place of last drink (POLD) data from
      alcohol violators. Data sources were from the Redlands Police Department: DUI
      arrests for drivers under age 21 years and drivers age 21 or older; alcohol
      related calls for service; public intoxication citations; and place of last drink
      surveys. Comparable data from control communities in California were not
      available at the time of the analyses. RESULTS: Responsible Redlands Initiatives
      appeared to be carried out as planned. There was a statistically significant
      decrease in DUI arrests for drivers 21 and older from preintervention to
      postintervention (p < .001), in alcohol-related calls for service (p < .001), in
      loud music calls for service (p = .06), and in public intoxication citations (p <
      .001). There were decreases in underage drinking violations and in DUIs for under
      age 21 drivers, but the numbers were too small for chi-squared statistical tests.
      CONCLUSIONS: "Responsible Redlands" interventions were associated with several
      significant decreases in outcome measures from preintervention to
      postintervention. Communities that consider these initiatives in combination
      (social host and deemed approved ordinances; minor-decoy and shoulder-tap
      operations; DUI checkpoints and saturation patrols; RBS training; use of ID
      scanners and a public information campaign to report loud drinking parties) can
      expect to experience potential decreases in alcohol-related harm.

PMID- 29584486
TI  - Novel method of estimating AROC using an injury risk curve for biomechanical
      injury metric selection.
AB  - OBJECTIVE: Area under the receiver operating characteristic (AROC) is commonly
      used to evaluate an injury metric's ability to discriminate between injury and
      noninjury cases. However, AROC has limitations and may not handle censored data
      sets adequately. Survival methodology creates robust estimates of injury risk
      curves (IRCs) which accommodate censored data. We developed an observation
      adjusted ROC (oaROC), an AROC-like statistic calculated from the IRC. METHODS:
      oaROC uses an observational distribution and an IRC to measure true positive rate
      (TPR) and false positive rate (FPR). The oaROC represents what the AROC would be
      with a large number of observations sampled from the IRC. We verified this using
      a limit test with simulated data sets at various sample sizes drawn from an
      assumed "true" IRC. For each sample size, 5,000 different data sets were created;
      a conventional AROC was calculated for each data set and compared with the single
      oaROC, which was calculated from the "true" IRC and not dependent on sample size.
      RESULTS: The oaROC, calculated from the simulated IRC, was 0.911. At a sample
      size of 20, the mean AROC was 0.930 (2.0% difference). At a sample size of 1,000,
      the mean AROC was 0.9114 (0.02% difference). CONCLUSION: We verified that AROC
      approaches the oaROC with increasing sample sizes, and oaROC presents a measure
      of IRC discriminatory ability. Survival methodology can estimate IRCs using
      censored observations and the oaROC was designed with this in mind. The oaROC may
      be a useful measure of discrimination for data sets containing censored data.
      Further investigation is needed to evaluate oaROC calculated from estimated IRCs.

PMID- 29584487
TI  - Comparison of outlier heartbeat identification and spectral transformation
      strategies for deriving heart rate variability indices for drivers at different
      stages of sleepiness.
AB  - OBJECTIVE: Appropriate preprocessing for detecting and removing outlier
      heartbeats and spectral transformation is essential for deriving heart rate
      variability (HRV) indices from cardiac monitoring data with high accuracy. The
      objective of this study is to evaluate agreement between standard preprocessing
      methods for cardiac monitoring data used to detect outlier heartbeats and perform
      spectral transformation, in relation to estimating HRV indices for drivers at
      different stages of sleepiness. METHODS: The study analyzed more than 3,500 5-min
      driving epochs from 76 drivers on a public motorway in Sweden.
      Electrocardiography (ECG) data were recorded in 3 studies designed to evaluate
      the physiological differences between awake and sleepy drivers. The Pan-Tompkins
      algorithm was used for peak detection of heartbeats from ECG data. Two standard
      methods were used for identifying outlier heartbeats: (1) percentage change (PC),
      where outliers were defined as interbeat interval deviating >30% from the mean of
      the 4 previous intervals, and (2) standard deviation (SD), where outliers were
      defined as interbeat interval deviating >4 SD from the mean interval duration in
      the current epoch. Three standard methods were used for spectral transformation,
      which is needed for deriving HRV indices in the frequency domain; these methods
      were (1) the Fourier transform; (2) an autoregressive model; and (3) the Lomb
      Scargle periodogram. The preprocessing methods were compared quantitatively and
      by assessing agreement between estimations of 13 common HRV indices using Bland
      Altman plots and paired Student's t-tests. RESULTS: The PC method detected more
      than 4 times as many outliers (0.28%) than SD (0.065%). Most HRV indices derived
      using different preprocessing methods exhibited significant systematic (P <.05)
      and substantial random variations. CONCLUSIONS: The standard preprocessing
      methods for HRV data for outlier heartbeat detection and spectral transformation
      show low levels of agreement. This finding implies that, prior to designing
      algorithms for detection of sleepy drivers based on HRV analysis, the impact of
      different preprocessing methods and combinations thereof on driver sleepiness
      assessment needs to be studied.

PMID- 29584488
TI  - Functional outcomes of thoracic injuries in pediatric and adult occupants.
AB  - OBJECTIVE: To develop a disability metric for motor vehicle crash (MVC) thoracic
      injuries and compare functional outcomes between pediatric and adult populations.
      METHODS: Disability risk (DR) was quantified using Functional Independence
      Measure (FIM) scores within the National Trauma Data Bank (NTDB) for the top 95%
      most frequently occurring AIS 2, 3, 4, and 5 thoracic injuries in NASS-CDS 2000
      2011. The NTDB contains a truncated form of the FIM score, including three items
      (self-feed, locomotion, and verbal expression), each graded from full functional
      dependence to full functional independence. Pediatric (ages 7-18 years), adult
      (19-45), middle-aged adult (46-65), and older adult (66+) MVC occupants were
      classified as disabled or not disabled based on the FIM scale. The DR was
      calculated for each injury within each age group by dividing the number of
      patients who were disabled that sustained the specific injury by the number of
      patients who sustained the specific injury. To account for the impact of more
      severe co-injuries, a maximum Abbreviated Injury Scale (MAIS) adjusted DR
      (DRMAIS) was also calculated. DR and DRMAIS could range from 0 (0% disability
      risk) to 1 (100% disability risk). RESULTS: The mean DRMAIS for MVC thoracic
      injuries was 20% for pediatric occupants, 22% for adults, 29% for middle-aged
      adults, and 43% for older adults. Older adults possessed higher DRMAIS values for
      diaphragm laceration/rupture, heart laceration, hemo/pneumothorax, lung
      contusion/laceration, rib fracture, and sternum fracture compared to the other
      age groups. The pediatric population possessed a higher DRMAIS value for flail
      chest compared to the other age groups. CONCLUSIONS: Older adults had
      significantly greater overall disability than each of the other age groups for
      thoracic injuries. The developed disability metrics are important in quantifying
      the significant burden of injuries and loss of quality life years. Such metrics
      can be used to better characterize severity of injury and further the
      understanding of age-related differences in injury outcomes, which can impact
      future age-specific modifications to AIS.

PMID- 29584489
TI  - Trends in child passenger safety practices in Indiana from 2009 to 2015.
AB  - OBJECTIVE: This study reviews trends in rear-facing direction, top tether use,
      booster seat use, and seating position for children 12 years or younger among
      motor vehicle passengers in Indiana. METHODS: This is an observational, cross
      sectional survey of drivers transporting children 15 years and younger collected
      at 25 convenience locations randomly selected in Indiana during summers of 2009
      2015. Observations were conducted by certified child passenger safety technicians
      (CPST). As the driver completed a written survey collecting demographic data on
      the driver, the CPST recorded the child demographic data, vehicle seating
      location, the type of restraint, direction the car safety seat (CSS) was facing,
      and use of the CSS harness or safety belt as appropriate. Data were analyzed for
      infants and toddlers younger than 24 months, children in forward-facing CSS,
      booster seat use, and seating position for children 12 years or younger. RESULTS:
      During the study period, 4,876 drivers were queried, and 7,725 children 15 years
      and younger were observed in motor vehicles. Between 2009 and 2015, 1,115 infants
      and toddlers (age birth to 23 months) were observed in motor vehicles. For
      infants <1 year, rear-facing increased from 84% to 91%. During the study years
      the greatest increase in rear facing was for toddlers age 12-17 months (12-61%).
      Rear facing for those from 18-23 months did not significantly change. Of the
      1,653 vehicles observed with a forward-facing car seat, using either the seat
      belt system or lower anchors, an average of 27% had the top tether attached. For
      installations of forward-facing seats using the lower anchor, 66% employed the
      top tether. Among children age 4-7 years observed booster seat use decreased from
      72% to 65% during the observation period. Finally, for vehicle seating position,
      in our sample, more than 85% of children 12 years or younger were seated in a
      rear seat vehicle position. Unfortunately, 31% of 8- to 12-year-old children were
      observed in the front seat. CONCLUSIONS: Overall, these trends demonstrate an
      improvement in child passenger safety practices among Indiana drivers. However,
      this study illuminates areas to improve child passenger safety, such as rear
      facing for toddlers 18 to 23 months, increasing top tether use, booster seat use,
      and an emphasis on rear seat position for children 8 to 12 years. This
      information can be used by primary care providers and child passenger safety
      technicians and other child passenger safety advocates to develop counseling
      points and targeted educational campaigns.

PMID- 29584490
TI  - Does obesity affect the position of seat belt loading in occupants involved in
      real-world motor vehicle collisions?
AB  - OBJECTIVE: Previous work has shown that the lap belt moves superior and forward
      compared to the bony pelvis as body mass index (BMI) increases. The goal of this
      project was to determine whether the location of lap belt loading is related to
      BMI for occupants who sustained real-world motor vehicle collisions (MVCs).
      METHODS: A national MVC database was queried for vehicle occupants over a 10-year
      period (2003-2012) who were at least 16 years old, restrained by a 3-point seat
      belt, sitting in the front row, and involved in a front-end collision with a
      change in velocity of at least 56 km/h. Cases were excluded if there was not an
      available computed tomography (CT) scan of the abdomen. CT scans were then
      analyzed using adipose enhancement of 3-dimensional reconstructions. Scans were
      assessed for the presence a radiographic seat belt sign (rSBS), or subcutaneous
      fat stranding due to seat belt loading. In scans in which the rSBS was present,
      anterior and superior displacement of rSBS from the anterior-superior iliac spine
      (ASIS) was measured bilaterally. This displacement was correlated with BMI and
      injury severity. RESULTS: The inclusion and exclusion criteria yielded 151 cases
      for analysis. An rSBS could definitively be identified in 55 cases. Cases in
      which occupants were older and had higher BMI were more likely to display an
      rSBS. There was a correlation between increasing BMI and anterior rSBS
      displacement (P <.01 and P <.01, right and left, respectively). There was no
      significant correlation between BMI and superior displacement of the rSBS (P =.46
      and P =.33, right and left, respectively). When the data were examined in terms
      of relating increasing superior displacement of the lap belt with Injury Severity
      Scale (P =.34) and maximum Abbreviated Injury Score (AIS) injury severity (P
      =.63), there was also no significant correlation. CONCLUSION: The results from
      this study demonstrated that anterior displacement of the radiographic seat belt
      sign but not superior displacement increased with higher BMI. These results
      suggest that obesity may worsen horizontal position but not the vertical position
      of the lap belt loading during real-world frontal MVCs.

PMID- 29584491
TI  - Active muscle response contributes to increased injury risk of lower extremity in
      occupant-knee airbag interaction.
AB  - OBJECTIVE: Recent field data analysis has demonstrated that knee airbags (KABs)
      can reduce occupant femur and pelvis injuries but may be insufficient to decrease
      leg injuries in motor vehicle crashes. An enhanced understanding of the
      associated injury mechanisms requires accurate assessment of physiological-based
      occupant parameters, some of which are difficult or impossible to obtain from
      experiments. This study sought to explore how active muscle response can
      influence the injury risk of lower extremities during KAB deployment using
      computational biomechanical analysis. METHODS: A full-factorial matrix,
      consisting of 48 finite element simulations of a 50th percentile occupant human
      model in a simplified vehicle interior, was designed. The matrix included 32 new
      cases in combination with 16 previously reported cases. The following influencing
      factors were taken into account: muscle activation, KAB use, KAB design, pre
      impact seating position, and crash mode. Responses of 32 lower extremity muscles
      during emergency braking were replicated using one-dimensional elements of a Hill
      type constitutive model, with the activation level determined from inverse
      dynamics and validated by existing volunteer tests. Dynamics of unfolding and
      inflating of the KABs were represented using the state-of-the-art corpuscular
      particle method. Abbreviated Injury Scale (AIS) 2+ injury risks of the knee-thigh
      hip (KTH) complex and the tibia were assessed using axial force and resultant
      bending moments. With all simulation cases being taken together, a general linear
      model was used to assess factor significance (P <.05). RESULTS: As estimated by
      the regression model across all simulation cases, use of KABs significantly
      reduced axial femur forces by 4.74 +/- 0.43 kN and AIS 2+ injury risk of KTH by
      47 +/- 6% (P <.05) but did not provide substantial change to injury risk of leg
      fractures. Muscle activation significantly increased axial force and bending
      moment of the femur (3.87 +/- 0.38 kN and 64.3 +/- 5.9 Nm), the tibia (1.49 +/-
      0.12 kN and 43.0 +/- 6.4 Nm), and the resultant probability of AIS 2+ tibia
      injuries by 36 +/- 6% regardless of KAB use and crash scenario. Specifically,
      when counting on a relative scale, muscle activation exhibited more prominent
      elevation of injury risk for in-position occupants than out-of-position
      occupants. In a representative crash scenario-that is, using a bottom-deployed
      KAB in a nearside oblique impact-muscle bracing of the right leg may lead to 2.6
      times higher tibia fracture risk than being relaxed for an out-of-position
      occupant and 5.4 times higher for an in-position occupant. DISCUSSION AND
      CONCLUSIONS: The mechanism of higher leg injuries in the presence of KAB
      deployment in real-world crashes can be interpreted by the increased effective
      body mass, axial compression along the shafts of long bones, and altered pre
      impact posture due to muscle contraction. The present analysis suggests that
      active muscle response can increase the risk of lower extremity injury during
      occupant-KAB interaction. This study demonstrated the feasibility of advanced
      human models to investigate the influence of physiologically based parameters on
      injury outcomes evidenced in field study and insight from computational
      examination on human variability for development of future restraint systems.
      Future efforts are recommended on realistic vehicle and restraint environment and
      advanced modeling strategies toward a full understanding of KAB efficacy.

PMID- 29584492
TI  - Differences in the protective capabilities of bicycle helmets in real-world and
      standard-specified impact scenarios.
AB  - OBJECTIVE: The purpose of this study was to investigate relative differences in
      impact attenuation capabilities of bicycle helmets under real-world impact
      conditions and safety standard-specified conditions using a standard rig.
      METHODS: A Consumer Product Safety Commission (CPSC) test rig was used to impact
      10 helmet models of varied design. Impact configurations included 2 locations and
      2 velocities. A frontal rim location (inferior to the standard-defined test area)
      and a temporal location were selected to reflect common cyclist impacts. An
      impact velocity of 3.4 m/s, an average normal impact velocity in cyclist
      accidents, was selected, as well as the CPSC standard velocity of 6.2 m/s. Four
      samples per helmet model were subjected to each of the 4 impact configurations
      once (randomized test order per sample), resulting in 160 drop tests. Peak linear
      acceleration (PLA) and head injury criterion (HIC)-based Abbreviated Injury Scale
      (AIS) >= 4 brain injury risk were determined and compared across helmets and
      impact configurations using analysis of variance. Other impact characteristics
      such as duration, effective liner stiffness, and energy dissipated were also
      calculated from acceleration data. RESULTS: Helmet performance varied
      significantly between models. PLA ranged from 78 to 169 g at 3.4 m/s (0-2% AIS >=
      4 brain injury risk) and 165-432 g (10-100% risk) at 6.2 m/s. Temporal impacts
      resulted in higher PLAs than frontal impacts, likely due to increased effective
      liner stiffness. However, 2 helmets exceeded the CPSC pass-fail threshold (300 g)
      at the frontal rim location, producing >70% risk. Force-displacement curves
      suggest that bottoming-out occurred in these impacts. Aside from bottoming-out
      cases, helmets that performed worse in one impact configuration tended to perform
      worse in others, with non-road-style helmets among the worst. CONCLUSIONS: The 10
      bicycle helmets tested produced considerable differences in their protective
      capabilities under both real-world and standard-specified conditions on the CPSC
      rig. Risk of severe brain injury varied widely between helmets at the standard
      impact velocity, whereas the common, lower severity impacts produced PLAs
      associated with concussion. Helmets of a nonroad style generally performed worse
      across configuration. The temporal location produced higher risks for most
      helmets, although some helmets were found to offer inadequate protection at the
      helmet rim. Because this is a commonly impacted location in cyclist accidents,
      there may be benefit to expanding the testable area in standards to include the
      rim. Results from this study demonstrate the value in testing nonstandard
      conditions and can be used to inform standards testing and helmet design.

PMID- 29584494
TI  - Frontal and oblique crash tests of HIII 6-year-old child ATD using real-world,
      observed child passenger postures.
AB  - OBJECTIVE: The aim of this study was to evaluate the consequences of frontal and
      oblique crashes when positioning a Hybrid III (HIII) 6-year-old child
      anthropometric test device (ATD) using observed child passenger postures from a
      naturalistic driving study (NDS). METHODS: Five positions for booster-seated
      children aged 4-7 years were selected, including one reference position according
      to the FMVSS 213 ATD seating protocol and 4 based on real-world observed child
      passenger postures from an NDS including 2 user positions with forward tilting
      torso and 2 that combined both forward and lateral inboard tilting of the torso.
      Seventeen sled tests were conducted in a mid-sized vehicle body at 64 km/h
      (European New Car Assessment Programme [Euro NCAP] Offset Deformable Barrier
      [ODB] pulse), in full frontal and oblique (15 degrees ) crash directions. The
      rear-seated HIII 6-year-old child ATD was restrained on a high-back booster seat.
      In 10 tests, the booster seat was also attached with a top tether. In the oblique
      tests, the ATD was positioned on the far side. Three camera views and ATD
      responses (head, neck, and chest) were analyzed. RESULTS: The shoulder belt
      slipped off the shoulder in all ATD positions in the oblique test configuration.
      In full frontal tests, the shoulder belt stayed on the shoulder in 3 out of 9
      tests. Head acceleration and neck tension were decreased in the forward leaning
      positions; however, the total head excursion increased up to 210 mm compared to
      te reference position, due to belt slip-off and initial forward leaning position.
      CONCLUSIONS: These results suggest that real-world child passenger postures may
      contribute to shoulder belt slip-off and increased head excursion, thus
      increasing the risk of head injury. Restraint system development needs to include
      a wider range of sitting postures that children may choose, in addition to the
      specified postures of ATDs in seating test protocols, to ensure robust
      performance across diverse use cases. In addition, these tests revealed that the
      child ATD is limited in its ability to mimic real-world child passenger postures.
      There is a need to develop child human body models that may offer greater
      flexibility for these types of crash evaluations.

PMID- 29584493
TI  - Numerical investigation of driver lower extremity injuries in finite element
      frontal crash reconstruction.
AB  - OBJECTIVE: Lower extremity injuries are the most frequent Abbreviated Injury
      Scale (AIS) 2 injury for drivers in frontal crashes. The objective was to
      reconstruct 11 real-world motor vehicle crashes (2 with AIS 2+ distal lower
      extremity injury and 9 without lower extremity injury) and to analyze the vehicle
      parameters and driver attributes that affect injury risk. METHODS: Eleven frontal
      crashes were reconstructed with a finite element simplified vehicle model (SVM)
      using a semi-automated optimization method. The SVM was tuned to each
      corresponding vehicle and the Total HUman Model for Safety (THUMS) Ver 4.01 was
      scaled and positioned in a baseline configuration to mimic the documented
      precrash driver posture. The event data recorder crash pulse was applied as the
      boundary condition for each case. Additionally, for the 2 cases with lower
      extremity injury, 120 simulations to quantify the uncertainty and response
      variation were performed varying the following parameters using a Latin hypercube
      design of experiment (DOE): seat track position, seatback angle, steering column
      angle, steering column position, and D-ring height. Injury metrics implemented
      within THUMS were calculated from the femur, tibia, and ankle and cross-compared
      among the 11 baseline cases using tibia index and multiple injury risk functions.
      Kinetic and kinematic data from the 120-simulation DOE were analyzed and fit to
      regression models to examine any causal relationship between occupant positioning
      and lower extremity injury risk. RESULTS: Of the 11 real-world crashes, both
      cases with lower extremity injuries resulted in elevated tibia axial forces and
      resultant bending moments, compared to the 9 cases without lower extremity
      injury. The average tibia index of the 2 cases with distal lower extremity injury
      (left: 1.79; right: 1.19) was higher than that in the 9 cases without lower
      extremity injury (left: 1.16, P =.024; right: 0.82, P =.024). An increased risk
      of AIS 2+ tibia shaft (33.6%), distal tibia and hindfoot (20.0%), as well as
      ankle malleolar (14.5%) fracture was also observed for the injured compared to
      the noninjured cases. Rearward seat track position, reclined seat back angle, and
      reduced seat height were correlated with elevated tibia axial force and increased
      tibia index, imposing additional lower extremity injury risk. CONCLUSIONS: This
      study provides a computational framework for assessing lower extremity injuries
      and elucidates the effect of precrash driver posture on lower extremity injury
      risk while accounting for vehicle parameters and driver attributes. Results from
      the study aid in the evaluation of real-world injury data, the understanding of
      factors contributing to injury risk, and the prevention of lower extremity
      injuries.

PMID- 29584495
TI  - Using naturalistic driving data to better understand the driving exposure and
      patterns of older drivers.
AB  - OBJECTIVE: The aging of the population in the United States and elsewhere has
      brought increasing attention to the issue of safe driving and mobility among
      older adults. The overall objective of this research was to use naturalistic data
      collection to better understand driving exposure and driving patterns, 2
      important contributors to crash risk. METHODS: Data came from a study conducted
      at the University of Michigan Transportation Research Institute as part of the
      Integrated Vehicle-Based Safety System (IVBSS) program. A total of 108 randomly
      sampled drivers took part, with the sample stratified by age and sex. The age
      groups examined were 20 to 30 (younger), 40 to 50 (middle-aged), and 60 to 70
      years old (older). Sixteen late-model Honda Accords were used as research
      vehicles and were driven by participants as their personal vehicles over the
      study period. Roughly the first 2 weeks of vehicle use comprised the baseline
      driving period, during which the IVBSS technologies were turned off (i.e., no
      warnings were presented to the drivers) but all onboard data were collected. For
      this article, only data from the baseline period were analyzed to limit any
      confounding effects that the safety technology may have had on driving behavior.
      RESULTS: Results indicated that when looking at age independent of sex, older
      drivers (age 60-70) took fewer trips, drove fewer minutes, were less likely to
      drive at night, and had fewer high decelerations and speeding events than the
      youngest age group (20-30). They were also less likely to drive during peak
      morning traffic and on high-speed roads than their middle-age counterparts (40
      50). Across all age groups, there were few differences by sex, with the exception
      that females drove fewer miles and fewer minutes and had fewer high decelerations
      than males. When both age and sex were taken into account, it was often the group
      of females age 60-70 that appeared to account for many of the age and sex
      differences found in driving exposure and patterns. CONCLUSIONS: Future research
      in this area would benefit from larger scale and longitudinal study designs so
      that changes in driving exposure and patterns over time among large samples of
      drivers could be examined.

PMID- 29584496
TI  - Evaluating drugged driving: Effects of exemplar pain and anxiety medications.
AB  - OBJECTIVE: Distracted and drug-influenced driving presents a major risk for
      traffic safety morbidity and mortality. As part of an ongoing research program,
      we examined the effects of a commonly prescribed combination of medications for
      pain relief: alprazolam, a benzodiazepine, and a hydrocodone preparation, a
      combination opiate and acetaminophen, on a simulated driving protocol. METHODS:
      Utilizing a within-subjects design, we recruited 8 healthy experienced drivers
      without major physical and psychological histories. Using a double-blind, placebo
      controlled crossover design, we administered placebo, alprazolam alone,
      hydrocodone/acetaminophen, and the combination of the 2 drugs in a standardized
      simulated driving protocol. Measures of lateral and longitudinal control were
      collected and the data were reduced and statically analyzed. RESULTS: The study
      observed clear detrimental effects of alprazolam on driving measures of lateral
      control and longitudinal control. Driving appeared to more aberrant at higher
      speeds and in rural scenarios. There were no statistical differences between
      hydrocodone and placebo. A measure of sedation showed that subjects rated
      alprazolam as more sedating than both hydrocodone and placebo. CONCLUSIONS: The
      findings suggest that impairing effects of this commonly prescribed combination
      of pharmacologic agents impact simulated driving performance. Negative changes in
      driving performance included measures of lateral and longitudinal control,
      although the deleterious effects on lateral control measures such as standard
      deviation of lane position (SDLP) were larger and more robust. Although the
      number of subjects was small, thus making it more difficult to draw conclusions
      on the narcotic effects, these results suggest that in this combination of
      central nervous system (CNS)-active drugs the benzodiazepine alprazolam accounted
      for the majority of impairing drug effects. The effect sizes associated with the
      hydrocodone preparation ranged from very small to medium. These results have
      potential implications for prescribing physicians and dispensing pharmacists,
      traffic safety experts, law enforcement officers, and patients themselves.

PMID- 29584497
TI  - Initial analysis of archived non-human primate frontal and rear impact data from
      the biodynamics data resource.
AB  - OBJECTIVE: The research objective was to conduct an initial analysis of non-human
      primate (NHP) data from frontal and rear impact events archived in the
      Biodynamics Data Resource (BDR) records of the Naval Biodynamics Laboratory
      (NBDL). These rare data, collected between 1973 and 1989, will inform the safety
      community of upper-end tolerance limits of NHP and may be related to severe crash
      scenarios. METHODS: Data from frontal and rear acceleration tests to 93 macaque
      NHP were examined. Each NHP was fully torso restrained, whereas the head-neck
      complex was unrestrained. Each NHP underwent between 1 and 21 total runs; 2 total
      runs was most common-a low-level run and then a high-level run. Following each
      impact exposure, the NHP was evaluated using a series of medical examinations.
      Now part of the legacy collection in the BDR, these evaluations were used to
      assess NHP exposures to be in one of 3 categories: noninjurious, injurious, or
      fatal. Using reported peak sled acceleration values, data were amenable to
      survival analysis statistical methodology to derive injury probability curves
      (IPCs). IPCs were derived for injury and fatality outcomes. RESULTS: Fatal
      injuries for both frontal and rear impacts were mostly at the cranio-vertebral
      junction. In addition to hemorrhage, fatal frontal and rear impact tests both
      produced predominantly atlanto-occipital dislocations, with and without spinal
      cord transection. After exclusions, IPCs were derived for frontal and rear impact
      for both (1) fatal outcome and (2) injurious outcome (any injury including fatal
      injury). For frontal impact, 53 NHP qualified with 5, 25, and 50% risk for
      fatality at 89, 105, and 114 peak sled Gs, respectively, and for injurious
      outcome at 70, 92, and 106 Gs, respectively. For rear impact, 34 NHP qualified
      with 5, 25, and 50% risk for fatality at 96, 122, 138 peak sled Gs, respectively,
      and for injurious outcome at 75, 99, and 115 Gs, respectively. CONCLUSIONS: The
      majority of injuries were at the cranio-vertebral junction, indicating that the
      inertial head mass caused a tensile loading mechanism to the cervical spine.
      These data may be used in conjunction with finite element modeling to estimate
      risks to the human population. The most direct application in the automotive
      environment could be to the well-restrained child. The Nij neck injury criteria,
      currently based on data from piglet studies, could also benefit because the NHP
      is a more accurate human surrogate. These types of tests are likely to never be
      repeated and will form an upper bound of tolerance information valuable to safety
      system designers.

PMID- 29584498
TI  - The influence of child restraint lower attachment method on protection offered by
      forward facing child restraint systems in oblique loading conditions.
AB  - OBJECTIVE: The research objective was to quantify the influence of child
      restraint lower attachment method on head kinematics, head impact potential, and
      head, neck, and thorax injury metrics for a child occupant secured in a forward
      facing child restraint system (FFCRS) in oblique side impacts. METHODS: Fifteen
      sled tests were conducted with a Q3s seated in an FFCRS secured to the center
      position on a production small SUV bench seat. Three lower attachment methods
      were evaluated: rigid ISOFIX, a flexible single loop lower anchors and tethers
      for children (LATCH) webbing routed through the vehicle belt path of the FFCRS,
      and dual flexible LATCH webbing attachments on either side of the FFCRS. All were
      tested with and without a tether with one repeat test in each test condition. The
      same model FFCRS was used for all tests; only the attachment method varied. The
      vehicle bench seat was fixed on the sled carriage at 80 degrees  (from full
      frontal). The input pulse was the proposed FMVSS 213 side impact pulse scaled to
      a 35 km/h delta-v. Two-way analysis of variance (ANOVA) was used to evaluate the
      effect of lower attachment and tether use on 3 outcome metrics: lateral head
      excursion, neck tension, and neck lateral bending. Data included anthropomorphic
      test dummy (ATD) head excursions, head linear accelerations and angular
      velocities, neck loads and moments, thoracic accelerations, lateral chest
      deflections, lower anchor loads, and tether webbing loads. ATD head kinematics
      were collected from 3-dimensional motion capture cameras. RESULTS: Results
      demonstrated a reduction in injury measures with the rigid ISOFIX and dual
      webbing attachment compared to the single webbing attachment with decreased
      lateral head excursions (331, 356, and 441 mm for the rigid ISOFIX, dual webbing,
      and single webbing systems, respectively, P <.0001), neck tension (1.4, 1.6, and
      2.2 kN, P <.01), and neck lateral bending (31.8, 38.7, and 38.0 Nm, P =.002). The
      tether had a greater influence on lateral head excursion for the FFCRS with
      flexible webbing attachments than those with the rigid attachment, with the
      tether forces being highest with the single webbing attachment. Lateral head
      excursions were significantly lower and lateral neck bending moments were
      significantly higher with tether use (P <.0001) across all lower attachments. The
      effect of tether on neck tension was mixed, only showing an increased effect with
      the rigid ISOFIX system. CONCLUSION: The CRS lower attachment system influenced
      occupant kinetics. The results indicate that CRS attached to the vehicle via
      rigid and dual webbing systems exhibit improved kinematics by reducing the
      rotation and tipping seen with the single webbing attachment. This leads to
      reduced lateral head excursions and neck tension values. The advantages of the
      tether in reducing lateral head excursion in side impacts are most pronounced
      with the flexible webbing attachments. With tether use low in the United States,
      a dual webbing type FFCRS attachment system may be a better attachment method
      than single webbing and provide a simpler engineering solution than rigid ISOFIX
      attachment.

PMID- 29584499
TI  - Burden of road traffic injuries related to delays in implementing safety belt
      laws in low- and lower-middle-income countries.
AB  - OBJECTIVE: Delayed implementation of effective road safety policies must be
      considered when quantifying the avoidable part of the fatal and nonfatal injuries
      burden. We sought to assess the avoidable part of disability-adjusted life years
      (DALYs) lost due to road traffic injuries related to delays in implementing road
      safety laws in low- and lower-middle-income countries. METHODS: We chose one
      country for each of the regions of the World Health Organization (WHO) and World
      Bank (WB) country income levels. We used freely available data sets (WHO,
      International Traffic Safety Data and Analysis Group, the WB). Delays in
      implementation were calculated until 2013, from the year mandatory use of safety
      belts by motor vehicle front seat occupants was first introduced worldwide. We
      used life expectancy tables and age groups as social values in the DALY
      calculation model. From the estimated total burden, avoidable DALYs were
      calculated using estimates of the effectiveness of seat belt laws on fatal and
      nonfatal injuries combined, as extracted from published international reviews of
      evidence. RESULTS: From the reference year 1972, implementation delays varied
      from 27 years (Uzbekistan) to 41 years in Bolivia (no seat belt law as of 2013).
      During delays, total absolute numbers of DALYs lost due to road traffic injuries
      reached 8,462,099 in Nigeria, 7,203,570 in Morocco, 4,695,500 in Uzbekistan,
      3,866,391 in Cambodia, 3,253,359 in Bolivia, and 3,128,721 in Sri Lanka. Using
      effectiveness estimates ranging from 3 to 20% reduction, the avoidable burden of
      road traffic injuries for car occupants was highest in Uzbekistan (avoidable part
      from 1.2 to 10.4%) and in Morocco (avoidable part from 1.5 to 12.3%). In
      countries where users of public transport and pedestrians were the most affected
      by the burden, the avoidable parts ranged from 0.5 to 4.4% (Nigeria) and from 0.5
      to 3.4% (Bolivia). Burden of road traffic injuries mostly affected motorcyclists
      in Sri Lanka and Cambodia where the avoidable parts were less than 2% in both
      countries. In all selected countries, burden of traffic injuries mostly affected
      men (about 80%) as well as young people (15-34 years). CONCLUSIONS: Despite
      limited data availability in low- and middle-income countries, the avoidable part
      of the burden related to delayed intervention is measurable. These results can be
      used to convince countries to avoid delaying the provision of better protection
      to road users.

PMID- 29584500
TI  - Comparison of three-point belt fit between humans and ATDs in rear seats.
AB  - OBJECTIVE: The anthropomorphic test devices (ATDs) in the Hybrid III family are
      widely used as human surrogates to test the crash performance of vehicles. A
      previous study demonstrated that passenger belt fit in rear seats was affected by
      high body mass index (BMI) and to a lesser extent by increased age. Specifically,
      the lap belt was worn higher and more forward as BMI and age increased. The
      objective of this study was to compare passenger belt fit to the belt fit
      achieved when installing the small female and midsize male Hybrid III adult ATDs
      using standard procedures. METHODS: The ATDs were installed using standardized
      procedures in the same conditions previously used with volunteers. Belt fit was
      measured using methods analogous to those used for the volunteers. Comparative
      human belt fit values were obtained by using regression analysis with the
      volunteer data to calculate the mean expected belt fit for people the same size
      as the ATDs. RESULTS: For the small female ATD, the upper edge of the lap belt
      was on average 59 mm forward and 11 mm above the anterior-superior iliac spine
      (ASIS) landmark on the ATD pelvis bone. In contrast, the belt position for
      similar size passengers was 17 mm forward and 22 mm above the ASIS. For the
      midsize male ATD, the belt was 34 mm forward and 10 mm above the ASIS. For
      similar size passengers, the position was 38 mm forward and 44 mm above the ASIS.
      For context, the belt width in this study was 38 mm. DISCUSSION: The results
      suggest that the lap belt fit obtained by ATDs is more idealized but more
      repeatable compared to that achieved by similar size passengers. Future
      standardization efforts should consider investigating whether new belt
      positioning procedures with ATDs may improve the biofidelity of ATD response.

PMID- 29584501
TI  - Quality of head injury coding from autopsy reports with AIS (c) 2005 update 2008.
AB  - : ABSTACT Objective: Coding injuries from autopsy reports of traffic accident
      victims according to Abbreviated Injury Scale AIS (c) 2005 update 2008 [1] is
      quite time consuming. The suspicion arose, that many issues leading to discussion
      between coder and control reader were based on information required by the AIS
      that was not documented in the autopsy reports. METHODS: To quantify this
      suspicion, we introduced an AIS-detail-indicator (AIS-DI). To each injury in the
      AIS Codebook one letter from A to N was assigned indicating the level of detail.
      Rules were formulated to receive repeatable assignments. This scheme was applied
      to a selection of 149 multiply injured traffic fatalities. The frequencies of
      "not A" codes were calculated for each body region and it was analysed, why the
      most detailed level A had not been coded. As a first finding, the results of the
      head region are presented. RESULTS: 747 AIS head injury codes were found in 137
      traffic fatalities, and 60% of these injuries were coded with an AIS-DI of level
      A. There are three different explanations for codes of AIS-DI "not A": Group 1
      "Missing information in autopsy report" (5%), Group 2 "Clinical data required by
      AIS" (20%), and Group 3 "AIS system determined" (15%). Groups 1 and 2 show
      consequences for the ISS in 25 cases. Other body regions might perform
      differently. CONCLUSIONS: The AIS-DI can indicate the quality of the underlying
      data basis and, depending on the aims of different AIS users it can be a helpful
      tool for quality checks.

PMID- 29584502
TI  - An insight of World Health Organization (WHO) accident database by cluster
      analysis with self-organizing map (SOM).
AB  - OBJECTIVE: Road crashes are increasing every year in low- and middle-income
      countries compared to high-income countries, which show decreasing trends. One
      theory may be because of differences in enforcement of laws, vehicle safety, road
      standards, and many other factors. A detailed review was made of 5 death trends
      (total number of deaths/100,000 population and percentages of 4-wheeler,
      pedestrian, motorized 2/3-wheeler, bicyclist) and the underlying patterns in
      different countries and regions across the world. This review was done to
      understand the main reasons for the variances to focus on efficient improvement
      strategies related to future vehicle and road safety issues. METHODS: A self
      organizing map (SOM) technique is used to map the nonlinear relationships among
      different attributes. Overall, 176 countries with 44 attributes were considered
      from the World Health Organization's (WHO) Global Status Report on Road Traffic
      Crashes database. Of the 44 attributes, 5 related to accident deaths were
      considered as response attributes. RESULTS: Very distinct and unique cause-effect
      patterns for 3 clusters were observed from SOM results. High-income countries
      were found to have a lower total number of deaths/100,000 population. One theory
      espouses that this was due to those countries maintaining high vehicle standards
      and policies, whereas it was quite a different situation for low-income
      countries. Even though helmet laws were available in Association of South East
      Asian Nations + 6 (ASEAN + 6) countries, the percentage of 2/3-wheeler deaths may
      be higher due a lack of enforcement of those laws. Percentage of deaths involving
      4-wheeler vehicles was higher in certain countries in the Persian Gulf, the
      United States, Australia, and New Zealand. This may be due to the fact that these
      countries have a number of rural areas where drivers drive at highway speeds
      versus some lower income countries with more urban areas where drivers operate
      vehicles at slower speeds. Countries with a lack of laws protecting bicyclists
      saw higher death percentages among bicyclists. The percentage of bicyclist deaths
      was also higher in areas with no helmet requirement and no investment in
      infrastructure improvements. The percentage of pedestrian deaths was high when
      there was no policy to separate road users, especially in low-income African
      countries. Deaths can be reduced by enforcement of laws and practicing good
      safety standards related to road traffic. CONCLUSIONS: Future vehicle and road
      safety strategies should consider using advanced statistical tools like SOM to
      advance safety. Based on a triple-layer (vehicle, infrastructure, and society)
      safety approach, strict regulations and enforcement are effective measures to
      reduce fatalities in low- and middle-income countries. On the other hand,
      introduction of more advanced vehicle technologies will be useful in countries
      with high gross national incomes (GNIs). Hence, a proper balance of different
      countermeasures based on economic zones could be effective to reduce total world
      traffic casualties.

PMID- 29584503
TI  - Influence of morphological variations on cervical spine segmental responses from
      inertial loading.
AB  - OBJECTIVES: The objective of this study was to investigate the influence of
      morphological variations in osteoligamentous lower cervical spinal segment
      responses under postero-anterior inertial loading. METHODS: A parametric finite
      element model of the C5-C6 spinal segment was used to generate models. Variations
      in the vertebral body and facet depth (anteroposterior), posterior process
      length, intervertebral disc height, facet articular process height and slope,
      segment orientation ranging from lordotic to straight, and segment size were
      parameterized. These variations included male-female differences. A Latin
      hypercube sampling method was used to select parameter values for model
      generation. Forces and moments associated with the inertial loading were applied
      to the generated model segments. The 7 parameters were grouped as local or global
      depending on the number of spinal components involved in the shape variation.
      Four output responses representing overall segmental and soft tissue responses
      were analyzed for each model variation: response angle of the segment, anterior
      longitudinal ligament stretch, anterior capsular ligament stretch, and facet
      joint compression in the posterior region. Pearson's correlation coefficient was
      used to compute the correlations of these output responses with morphological
      variations. RESULTS: Fifty models were generated from the parameterized model
      using a Latin hypercube sampling technique. Variation in response angle among the
      models was 4 degrees  and was most influenced by change in the combined dimension
      of vertebral body and facet depth, followed by size of the segment. The maximum
      anterior longitudinal ligament stretch varied between 0.1 and 0.3 and was
      strongly influenced by the change in the segment orientation. The anterior facet
      joint region sustained tension, whereas the posterior region sustained
      compression. For the anterior capsular ligament stretch, the most influential
      global variation was segment orientation, whereas the most influential local
      variations were the facet height and facet angle parameters. In the case of
      posterior facet joint compression, segment orientation was again most
      influential, whereas among the local variations, the facet angle had the most
      influence. CONCLUSION: Shape variations in the intervertebral disc influenced
      segmental rotation and ligament responses; however, the influence of shape
      variations in the facet joint was confined to capsular ligament responses.
      Response angle was most influenced by the vertebral body depth variations,
      explaining greater segmental rotations in female spines. Straighter spine
      segments sustained greater posterior facet joint compression, which may offer an
      explanation for the higher incidence of whiplash-associated disorders among
      females, who exhibit a straighter cervical spine. The anterior longitudinal
      ligament stretch was also greater in straighter segments. These findings indicate
      that the morphological features specific to the anatomy of the female cervical
      spine may predispose it to injury under inertial loading.

PMID- 29584504
TI  - Top tether effectiveness during side impacts.
AB  - OBJECTIVE: Few studies have looked at the effectiveness of the top tether during
      side impacts. In these studies, limited anthropomorphic test device (ATD) data
      were collected and/or few side impact scenarios were observed. The goal of this
      study was to further understand the effects of the top tether on ATD responses
      and child restraint system (CRS) kinematics during various side impact
      conditions. METHODS: A series of high-speed near-side and far-side sled tests
      were performed using the FMVSS213 side impact sled buck and Q3s ATD. Tests were
      performed at both 10 degrees  and 30 degrees  impacts with respect to the pure
      lateral direction. Two child restraints, CRS A and CRS B, were attached to the
      bench using flexible lower anchors. Each test scenario was performed with the
      presence and absence of a top tether. Instrumentation recorded Q3s responses and
      CRS kinematics, and the identical test scenarios with and without a top tether
      attachment were compared. RESULTS: For the far-side lateral (10 degrees ) and
      oblique (30 degrees ) impacts, top tether attachment increased resultant head
      accelerations by 8-38% and head injury criterion (HIC15) values by 20-140%.
      However, the top tether was effective in reducing lateral head excursion by 5
      25%. For near-side impacts, the top tether resulted in less than 10% increases in
      both resultant head acceleration and HIC15 in the lateral impact direction. For
      near-side oblique impacts, the top tether increased HIC15 by 17.3% for CRS A and
      decreased it by 19.5% for CRS B. However, the injury values determined from both
      impact conditions were below current injury assessment reference values (IARVs).
      Additionally, the top tether proved beneficial in preventing forward and lateral
      CRS rotations. CONCLUSIONS: The results show that the effects of the top tether
      on Q3s responses were dependent on impact type, impact angle, and CRS. Tether
      attachments that increased head accelerations and HIC15 values were generally
      counterbalanced by a reduction in head excursion and CRS rotation compared to
      nontethered scenarios.

PMID- 29584505
TI  - A preliminary study of human model head and neck response to frontal loading in
      nontraditional occupant seating configurations.
AB  - OBJECTIVE: Computational human body models (HBMs) are nominally omnidirectional
      surrogates given their structural basis in human anatomy. As a result, such
      models are well suited for studies related to occupant safety in anticipated
      highly automated vehicles (HAVs). We utilize a well-validated HBM to study the
      head and neck kinematics in simulations of nontraditional occupant seating
      configurations. METHODS: The GHBMC M50-O v. 4.4 HBM was gravity settled into a
      generic seat buck and situated in a seated posture. The model was simulated in
      angular increments of 15 degrees clockwise from forward facing to rear facing. A
      pulse of 17.0 kph (NASS median) was used in each to simulate a frontal impact for
      each of the 13 seating configurations. Belt anchor points were rotated with the
      seat; the airbag was appropriately powered based on delta-V, and was not used in
      rear-facing orientations. Neck forces and moments were calculated. RESULTS: The
      30-degree oblique case was found to result in the maximum neck load and sagittal
      moment, and thus Neck Injury Criteria (NIJ). Neck loads were minimized in the
      rear facing condition. The moments and loads, however, were greatest in the
      lateral seating configuration for these frontal crash simulations. CONCLUSIONS:
      In a recent policy statement on HAVs, the NHTSA indicated that vehicle
      manufacturers will be expected to provide countermeasures that will fully protect
      occupants given any planned seating or interior configurations. Furthermore, the
      agency indicated that virtual tests using human models could be used to
      demonstrate such efficacy. While the results presented are only appropriate for
      comparison within this study, they do indicate that human models provide
      reasonable biomechanical data for nontraditional occupant seating arrangements.

PMID- 29584506
TI  - AIS scores in spine and spinal cord trauma: Epidemiological considerations.
AB  - BACKGROUND: The Abbreviated Injury Scale (AIS) is an internationally accepted
      coding system created by the Association for the Advancement of Automotive
      Medicine, utilized to code traumatic injuries as a function of severity, the
      latter often defined as mortality risk. Periodic reassessment of that risk is
      prudent, in light of advances in health care and relationship of nonanatomic
      factors to death. OBJECTIVE: The objective of this study was to reevaluate the
      risk of death associated with spine fractures with and without neurologic
      deficit, age factors associated with it, and the impact of hospital coding on the
      accuracy of these efforts. METHODS: Medical records and imaging of patients
      treated at a level 1 trauma center from 2014 through 2016 with discharge
      International Classification of Diseases, 10th revision (ICD-10) diagnoses of
      spinal trauma and spinal cord injury (SCI) were reviewed. Data were collected on
      demographics, complications, neurologic status, and outcomes. RESULTS: Three
      hundred seventy patients met the criteria for inclusion in this effort. Errors in
      ICD-10 discharge codes were seen in 45% of the cases, both false positive and
      negative. One hundred thirty-four patients, with a mean age of 45, were admitted
      with neurologic deficit. There were 8 SCI-related deaths; 2 were postoperative
      out of 110 undergoing surgical treatment. All deaths in this group were in
      patients with upper level SCI, with a mean age of 68. Ten patients had
      spontaneous neurologic improvement within 24 h. One hundred nineteen patients
      without deficit had AIS 2 scored fractures; there was one postoperative death out
      of 47 patients undergoing surgical treatment. One hundred seventeen patients
      without deficit suffered AIS 3 fractures; 66 underwent surgery without any
      deaths. There was one nonoperative death. Age and high quadriplegia were the only
      factors associated with mortality. CONCLUSIONS: Mortality risk in patients with
      deficit was associated more with age at injury than extent of anatomic injury.
      Spine trauma without neurologic deficit is benign in younger populations and AIS
      scores could be age adjusted. Mortality risk is higher in high cervical injuries
      with neurologic deficit and in the elderly. An incidental finding is that
      demographic studies based solely on discharge ICD coding may contain errors and
      should be considered critically.

PMID- 29584507
TI  - Trunk muscle recruitment patterns in simulated precrash events.
AB  - OBJECTIVES: To quantify trunk muscle activation levels during whole body
      accelerations that simulate precrash events in multiple directions and to
      identify recruitment patterns for the development of active human body models.
      METHODS: Four subjects (1 female, 3 males) were accelerated at 0.55 g (net Deltav
      = 4.0 m/s) in 8 directions while seated on a sled-mounted car seat to simulate a
      precrash pulse. Electromyographic (EMG) activity in 4 trunk muscles was measured
      using wire electrodes inserted into the left rectus abdominis, internal oblique,
      iliocostalis, and multifidus muscles at the L2-L3 level. Muscle activity evoked
      by the perturbations was normalized by each muscle's isometric maximum voluntary
      contraction (MVC) activity. Spatial tuning curves were plotted at 150, 300, and
      600 ms after acceleration onset. RESULTS: EMG activity remained below 40% MVC for
      the three time points for most directions. At the 150- and 300 ms time points,
      the highest EMG amplitudes were observed during perturbations to the left (-90
      degrees ) and left rearward (-135 degrees ). EMG activity diminished by 600 ms
      for the anterior muscles, but not for the posterior muscles. CONCLUSIONS: These
      preliminary results suggest that trunk muscle activity may be directionally tuned
      at the acceleration level tested here. Although data from more subjects are
      needed, these preliminary data support the development of modeled trunk muscle
      recruitment strategies in active human body models that predict occupant
      responses in precrash scenarios.

PMID- 29584508
TI  - Understanding fatal older road user crash circumstances and risk factors.
AB  - OBJECTIVE: This study used medicolegal data to investigate fatal older road user
      (ORU) crash circumstances and risk factors relating to four key components of the
      Safe System approach (e.g., roads and roadsides, vehicles, road users, and
      speeds) to identify areas of priority for targeted prevention activity. METHODS:
      The Coroners Court of Victoria's Surveillance Database was searched to identify
      coronial records with at least one deceased ORU in the state of Victoria,
      Australia, for 2013-2014. Information relating to the ORU, crash characteristics
      and circumstances, and risk factors was extracted and analyzed. RESULTS: The
      average rate of fatal ORU crashes per 100,000 population was 8.1 (95% confidence
      interval [CI] 6.0-10.2), which was more than double the average rate of fatal
      middle-aged road user crashes (3.6, 95% CI 2.5-4.6). There was a significant
      relationship between age group and deceased road user type (chi2(15, N = 226) =
      3.56, p < 0.001). The proportion of deceased drivers decreased with age, whereas
      the proportion of deceased pedestrians increased with age. The majority of fatal
      ORU crashes involved a counterpart (another vehicle: 59.4%; fixed/stationary
      object: 25.4%), and occurred "on road" (87.0%), on roads that were paved (94.2%),
      dry (74.2%), and had light traffic volume (38.3%). Road user error was identified
      by the police and/or coroner for the majority of fatal ORU crashes (57.9%), with
      a significant proportion of deceased ORU deemed to have "misjudged" (40.9%) or
      "failed to yield" (37.9%). CONCLUSIONS: Road user error was the most significant
      risk factor identified in fatal ORU crashes, which suggests that there is a
      limited capacity of the Victorian road system to fully accommodate road user
      errors. Initiatives related to safer roads and roadsides, vehicles, and speed
      zones, as well as behavioral approaches, are key areas of priority for targeted
      activity to prevent fatal older road user crashes in the future.

PMID- 29584509
TI  - Improvement of injury severity prediction (ISP) of AACN during on-site triage
      using vehicle deformation pattern for car-to-car (C2C) side impacts.
AB  - OBJECTIVE: The Advanced Automatic Crash Notification (AACN) system needs to
      predict injury accurately, to provide appropriate treatment for seriously injured
      occupants involved in motor vehicle crashes. This study investigates the
      possibility of improving the accuracy of the AACN system, using vehicle
      deformation parameters in car-to-car (C2C) side impacts. METHODS: This study was
      based on car-to-car (C2C) crash data from NASS-CDS, CY 2004-2014. Variables from
      Kononen's algorithm (published in 2011) were used to build a "base model" for
      this study. Two additional variables, intrusion magnitude and max deformation
      location, are added to Kononen's algorithm variables (age, belt usage, number of
      events, and delta-v) to build a "proposed model." This proposed model operates in
      two stages: In the first stage, the AACN system uses Kononen's variables and
      predicts injury severity, based on which emergency medical services (EMS) is
      dispatched; in the second stage, the EMS team conveys deformation-related
      information, for accurate prediction of serious injury. RESULTS: Logistic
      regression analysis reveals that the vehicle deformation location and intrusion
      magnitude are significant parameters in predicting the level of injury. The
      percentage of serious injury decreases as the deformation location shifts away
      from the driver sitting position. The proposed model can improve the sensitivity
      (serious injury correctly predicted as serious) from 50% to 63%, and overall
      prediction accuracy increased from 83.5% to 85.9%. CONCLUSION: The proposed
      method can improve the accuracy of injury prediction in side-impact collisions.
      Similar opportunities exist for other crash modes also.

PMID- 29584510
TI  - Bioimpedance Vector Analysis of Elite, Subelite, and Low-Level Male Volleyball
      Players.
AB  - PURPOSE: To establish a specific player profile on body-composition parameters
      and to provide a data set of bioelectric impedances values for male volleyball
      players. METHODS: The study included 201 athletes (age 26.1 [5.4] y, height 191.9
      [9.7] cm, weight 86.8 [10.8] kg) registered in the Italian volleyball divisions.
      The athletes were divided into 3 groups: The elite group comprised 75 players
      participating in the 1st (Super Lega) division, the subelite group included 65
      athletes performing in the 2nd (Serie A2) division, and the low-level group
      included 61 players participating in the 3rd (Serie B) division. Bioelectric
      impedance, body weight, and height of the athletes were measured in the second
      half of the competitive season. In addition, bioelectrical impedance vector
      analysis was performed. RESULTS: The elite group showed a greater amount of fat
      free mass (FFM) and total body water (TBW) and a lower fat mass (FM) than the
      subelite group (P < .05). In addition, the elite players were taller and heavier
      and had a higher FFM, FM, TBW, and body cellular mass than the low-level athletes
      (P < .05). Finally, the mean impedance vectors of the elite group significantly
      differed from those measured in the normal population and in the other 2 groups
      (P < .05). CONCLUSIONS: This study provides an original data set of body
      composition and bioelectric impedance reference values of elite male volleyball
      players. The results might be useful for interpretation of individual
      bioimpedance vectors and for defining target regions for volleyball players.

PMID- 29584511
TI  - Micro-computed tomographic evaluation of the effect of the final apical size
      prepared by rotary nickel-titanium files on the removal efficacy of hard-tissue
      debris.
AB  - Objective This study was performed to compare the removal efficacy of hard-tissue
      debris in mandibular first molars prepared to various apical sizes. Methods The
      mesial root canals of 40 extracted mandibular first molars were prepared by
      rotary nickel-titanium files to an apical size of #25/0.04 (Group #2504),
      #30/0.04 (Group #3004), #35/0.04 (Group #3504), and #40/0.04 (Group #4004).
      Irrigation was performed with 5.25% NaOCl and 17% EDTA. Micro-computed tomography
      was used to scan the samples before and after root canal preparation. Remnant
      hard-tissue debris was identified, quantified, and visualized three-dimensionally
      using shape recognition and image superimposition analysis, and the debris was
      mapped to its location. Results After preparation, 11.67%+/-2.99% of the root
      canals contained hard-tissue debris in Group #2504, 8.00%+/-2.71% in Group #3004,
      7.17%+/-2.88% in Group #3504, and 4.51%+/-1.61% in Group #4004. The amount of
      accumulated hard-tissue debris was significantly less in Group #4004 than in the
      other groups. However, there were no significant differences between Groups #3004
      and #3504. Conclusions An increased final apical size resulted in significantly
      lower debris accumulation. However, no root canal in any group was completely
      free from hard-tissue debris, and debris was mostly found in the isthmus of the
      mesial root canals.

PMID- 29584512
TI  - Acute prevertebral abscess secondary to intradiscal oxygen-ozone chemonucleolysis
      for treatment of a cervical disc herniation.
AB  - Objective We herein present a case involving a prevertebral abscess complicated
      by a spinal epidural abscess (SEA) secondary to intradiscal oxygen-ozone
      chemonucleolysis for treatment of a cervical disc herniation. Methods A 67-year
      old woman with a history of intradiscal oxygen-ozone chemonucleolysis developed
      numbness and weakness in her right upper and bilateral lower extremities followed
      by urinary retention. Her symptoms did not respond to intravenous antibiotics
      alone. Magnetic resonance imaging of the cervical region revealed an extensive
      SEA anterior to the spinal cord, spinal cord myelopathy due to anterior
      compression by the lesion, and a prevertebral abscess extending from C2 to T1.
      She underwent surgical drainage and irrigation. Results The patient was
      successfully treated with surgical drainage and systemic antibiotic therapy
      without kyphosis. Streptococcus intermedius was detected within the abscess. All
      clinical symptoms except for the sensory deficit in the left leg were relieved.
      Conclusions The safety of intradiscal oxygen-ozone therapy requires further
      assessment. High-dose intravenous antibiotics should be initiated empirically at
      the earliest possible stage of prevertebral and epidural abscesses. Surgical
      drainage may be a rational treatment choice for patients with a prevertebral
      abscess complicated by an SEA and spinal cord myelopathy.

PMID- 29584513
TI  - Three-by-Three Basketball: Inertial Movement and Physiological Demands During
      Elite Games.
AB  - PURPOSE: To determine the demands of elite male and female 3 * 3 basketball games
      and compare these between various competition levels. METHODS: A total of 361
      males and 208 females competing in the Under-18 World, Senior European, and World
      Championships and selected professional tournaments had game demands assessed by
      wearable technology (global positioning system, inertial measurement, heart rate)
      along with postgame blood lactate and perceived responses. Differences in the
      means were compared using magnitude-based inferences and reported with effect
      size and 90% confidence limits, along with the percentage difference (effect
      size; +/-90% confidence limits, %) of log-transformed data. RESULTS: PlayerLoadTM
      and PlayerLoad.min-1 during play was 127.5 (31.1) and 6.7 (1.5) for males and
      128.5 (32.0) and 6.5 (1.4) for females, respectively, with small differences
      between junior, senior, and professional levels. There were small differences in
      accelerations >3.5 m.s-1 between competition levels up to 0.31; +/-0.20, 6.9% for
      males and 0.29; +/-0.19, 10.8% for females and for decelerations >3.5 m.s-1,
      0.29; +/-0.19, 15.6% for males and 0.26; +/-0.19, 5.4% for females, with European
      Championships generally greater than other levels. Average game heart rate was
      165 (18) and 164 (12) beats.min-1 for males and females, with no difference
      between levels. Average rating of perceived exertion was 5.7 (2.1) and 5.4 (2.0)
      for males and females. CONCLUSIONS: 3 * 3 basketball games require high-speed
      inertial movements within limited distance, creating a relatively high
      physiological response. Practitioners working with 3 * 3 players should endeavor
      to focus on the attributes that will improve these player characteristics for
      greater success.

PMID- 29584514
TI  - The Same Story or a Unique Novel? Within-Participant Principal-Component Analysis
      of Measures of Training Load in Professional Rugby Union Skills Training.
AB  - PURPOSE: To identify which combination metrics of external and internal training
      load (TL) capture similar or unique information for individual professional
      players during skills training in rugby union using principal-component (PC)
      analysis. METHODS: TL data were collected from 21 male professional rugby union
      players across a competitive season. This included PlayerLoadTM, total distance,
      and individualized high-speed distance (>61% maximal velocity; all external TL)
      obtained from a microtechnology device (OptimEye X4; Catapult Innovations,
      Melbourne, Australia) that was worn by each player and the session rating of
      perceived exertion (RPE) (internal TL). PC analysis was conducted on each
      individual to extract the underlying combinations of the 4 TL measures that best
      describe the total information (variance) provided by the measures. TL measures
      with PC loadings (PCL) above 0.7 were deemed to possess well-defined
      relationships with the extracted PC. RESULTS: The findings show that from the 4
      TL measures, the majority of an individual's TL information (first PC: 55-70%)
      during skills training can be explained by session RPE (PCL: 0.72-0.95), total
      distance (PCL: 0.86-0.98), or PlayerLoad (PCL: 0.71-0.98). High-speed distance
      was the only variable to relate to the second PC (PCL: 0.72-1.00), which captured
      additional TL information (+19-28%). CONCLUSIONS: Findings suggest that
      practitioners could quantify the TL of rugby union skills training with one of
      PlayerLoad, total distance, or session RPE plus high-speed distance while
      limiting omitted information of the TL imposed during professional rugby union
      skills training.

PMID- 29584515
TI  - Track-structure simulations of energy deposition patterns to mitochondria and
      damage to their DNA.
AB  - PURPOSE: Mitochondria have been implicated in initiating and/or amplifying the
      biological effects of ionizing radiation not mediated via damage to nuclear DNA.
      To help elucidate the underlying mechanisms, energy deposition patterns to
      mitochondria and radiation damage to their DNA have been modelled. METHODS: Track
      structure simulations have been performed with PARTRAC biophysical tool for 60Co
      gamma-rays and 5 MeV alpha-particles. Energy deposition to the cell's
      mitochondria has been analyzed. A model of mitochondrial DNA reflecting
      experimental information on its structure has been developed and used to assess
      its radiation-induced damage. RESULTS: Energy deposition to mitochondria is
      highly inhomogeneous, especially at low doses. Although a dose-dependent fraction
      of mitochondria sees no energy deposition at all, the hit ones receive rather
      high amounts of energy. Nevertheless, only little damage to mitochondrial DNA
      occurs, even at large doses. CONCLUSION: Mitochondrial DNA does not represent a
      critical target for radiation effects. Likely, the key role of mitochondria in
      radiation-induced biological effects arises from the communication between
      mitochondria and/or with the nucleus. Through this signaling, initial
      modifications in a few heavily hit mitochondria seem to be amplified to a massive
      long-term effect manifested in the whole cell or even tissue.

PMID- 29584516
TI  - Effect of Intermittent Hypoxia Training for Dizziness: A Randomized Controlled
      Trial.
AB  - OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for
      dizziness. DESIGN: A single-blind, randomized controlled trial. All participants
      were recruited from a rehabilitation department in an acute university-affiliated
      hospital. INTERVENTION: Participants with dizziness were randomly assigned to two
      groups (IHT group and control group). The Dizziness Handicap Inventory (DHI),
      Activities-specific Balance Confidence Scale (ABC), Vertigo Visual Analog Scale
      (VVAS) were conducted at baseline, end of the 4th week. RESULTS: Among 52
      subjects, eighteen males and thirty four females, ages from 35 to 62 years old
      (mean +/- SD = 46.9 +/- 7.93). Time length since onset ranged from 12 months to
      34 months (20.2+/-7.15 months). DHI, ABC, VVAS scores and attack frequencies of
      dizziness were improved after IH training intervention in the end of 4th week.
      There were significant differences between IHT group and control group in DHI,
      ABC, VVAS scores and attack frequencies of dizziness in the end of 4th week
      (P<0.05). No adverse events occurred during the study. CONCLUSION: IHT could
      improve dizziness after intervention in end of 4th week. IHT could be the
      effective method for releasing dizziness.

PMID- 29584517
TI  - Electronic medical records and risk management in hospitals of Saudi Arabia.
AB  - OBJECTIVE: Electronic medical records systems and the associated risks have been
      well studied in developed countries; the same cannot be said for systems in
      developing countries. Previous research in Saudi Arabian health-care
      organizations has shown a low level of quality in hospital services due to
      ineffective risk management. The objective of this research is to apply the
      Systems Theoretic Accident Modelling and Processes (STAMP) risk management
      technique in Saudi Arabia and evaluate its implementation. PARTICIPANTS: The
      participating organization is a health-care organization in Saudi Arabia Methods:
      A two-phase case study was conducted. The first phase implemented the STAMP
      technique to identify and manage risks to the system. For the second phase, the
      STAMP technique was extended to include a checklist, to increase STAMP's
      capability to mitigate risks, and the process reapplied. RESULTS AND CONCLUSION:
      The results demonstrated that the inclusion of the STAMP Checklist reduced errors
      and prevented system failures compared to regular STAMP.

PMID- 29584518
TI  - Planned Load Reduction Versus Fixed Load: A Strategy to Reduce the Perception of
      Effort With Similar Improvements in Hypertrophy and Strength.
AB  - PURPOSE: To compare muscle thickness and 10-repetition maximum (10RM) between no
      load reduction and load reductions during 16 wk of resistance training. METHODS:
      A total of 21 moderately trained men (age 23.2 [4.2] y, body mass 75.1 [7.6] kg,
      height 175 [4] cm) were randomized into 1 of 3 exercise groups: control (CON, n =
      7), all sets with 10RM load; 5% load reduction (RED 5, n = 7); and 10% load
      reduction (RED 10, n = 7) for set 2 and set 3. The resistance training program
      consisted of completing 3 sets each of biceps and Scott curls, performed to
      volitional fatigue 3 d.wk-1. RESULTS: Volume load lifted over the 16 wk was
      similar among groups (CON, 38,495 [4397] kg; RED 5, 37,388 [3684] kg; RED 10,
      42,634 [6733] kg; P = .094). Muscle thickness increased in all groups (P < .001),
      with no differences noted among groups (P = .976). Biceps-curl and Scott-curl
      10RM increased in all groups (P < .001), with no differences noted among groups
      (Scott curl P = .238; biceps curl P = .401). Rating of perceived exertion (RPE)
      was significantly lower for RED 10 (6.8 [0.1]) than for CON (7.0 [0.1]; P < .001)
      or RED 5 (7.1 [0.1]; P = .001) for the Scott curl. RPE was significantly lower (P
      = .001) for the biceps curl in RED 10 (6.8 [0.3]) than in CON (7.3 [0.9]), with
      neither group different from RED 5 (7.0 [0.1]). CONCLUSIONS: Load reduction did
      not yield a difference in hypertrophy or 10RM as compared with CON. However, RED
      10 induced a significantly lower RPE. Thus, load reduction may be a beneficial
      strategy to reduce the perception of effort during training while achieving
      similar improvements in hypertrophy and strength.

PMID- 29584519
TI  - Physical health problems in people with psychosis: The issue for informal carers.
AB  - BACKGROUND: Reduced life expectancies are recorded in adults with psychotic
      disorders. Informal carers play key roles in improving illness outcomes for
      patients, including significantly reducing rates of relapse and hospitalisation.
      There is, however, a dearth of literature detailing carers' perspectives on
      physical health problems in the relatives they care for and implications for
      those in the caregiving role. The study sought to explore carers' subjective
      experiences of supporting a relative with psychosis and physical health problems.
      METHODS: Carers of adults with psychosis were interviewed individually, or as
      part of a group, about physical health problems in the relatives they care for.
      RESULTS: Five key themes were identified from the interviews that reflected (1)
      ubiquity of physical health problems in psychosis, (2) gaps in service provision
      for those living with mental and physical health problems, (3) carers' role in
      responding to service gaps, (4) difficult conversations and (5) impact on carer
      health. CONCLUSION: Service initiatives that are designed to improve patient
      physical health in psychosis should not overlook the role that informal carers
      might have in supporting this process. The implications that patient physical
      health problems present for carer well-being and the quality of the caregiving
      relationship in psychosis deserve further investigation.

PMID- 29584521
TI  - Policy and Legal Protection for Breastfeeding and Incarcerated Women in Canada.
AB  - Most incarcerated women in Canada are mothers. Because women are the fastest
      growing population in carceral facilities, protecting the rights of incarcerated
      women to breastfeed their children is increasingly important. There is
      considerable evidence that incarcerated women in Canada experience poor physical
      and mental health, isolation, and barriers to care. Incarcerated women and their
      children could benefit significantly from breastfeeding. This Insight in Policy
      explores policy and legal protection for breastfeeding in Canada as it relates to
      carceral facilities, considers key cases regarding breastfeeding rights among
      incarcerated women, and presents recommendations for policy development and
      advocacy. The Canadian Constitution and human rights legislation across Canada
      prohibits discrimination on the basis of gender and includes pregnancy and the
      possibility of becoming pregnant as a characteristic of gender. Some provinces
      note that breastfeeding is a characteristic of gender. Women's Wellness Within, a
      nonprofit organization providing volunteer perinatal support to criminalized
      women in Nova Scotia, conducted a scan of all provincial and territorial
      correctional services acts and the federal Corrections and Conditional Release
      Act: none mention breastfeeding. Protocols for breastfeeding during arrest and
      lockup by police were not available in any jurisdiction across Canada.
      International law, including the Convention on the Rights of the Child, the
      Nelson Mandela Rules, and the Bangkok Rules, have application to the rights of
      incarcerated breastfeeding women. The Inglis v. British Columbia (Minister of
      Public Safety) (2013) and Hidalgo v. New Mexico Department of Corrections (2017)
      decisions are pivotal examples of successful litigation brought forward by
      incarcerated mothers to advance breastfeeding rights. Improved application and
      understanding of existent law could advance breastfeeding rights.

PMID- 29584520
TI  - Coping, resilience and posttraumatic growth among Eritrean female refugees living
      in Norwegian asylum reception centres: A qualitative study.
AB  - BACKGROUND: The links between migration and health are well documented. Being a
      refugee exacerbates migrants' vulnerability through trauma and loss. The aim of
      this study is to identify sources of resilience, coping and posttraumatic growth
      in female Eritrean refugees living in Norwegian asylum reception centres. METHOD:
      The study had a qualitative, descriptive and explorative design with two focus
      group interviews and 10 individual in-depth interviews. Participants included 18
      female Eritrean refugees aged 18-60, who had obtained refugee status and were
      still living in an asylum reception centre. A content-focused hermeneutic
      analytic approach was used. RESULTS: Interviewees described the challenges of pre
      flight and flight trauma, conditions at the refugee centre, communication
      difficulties and the 'endless' waiting for transfer to a municipality. To cope,
      they found it helpful to focus on the future and to think positively. Fellowship
      with and support from fellow Eritrean refugees were essential as they became a
      proxy family and provided a strong ethnic identity. Their religious belief also
      helped them cope and gave them hope for the future. DISCUSSION: The interviewees
      in this study perceived their psychological problems as a normal reaction to what
      they had been through. Religious belief was an important resilience factor, as
      was social support, especially from peers. CONCLUSION: The interviewees' coping
      was based on the realization of their psychological reactions being normal while
      doing their utmost to focus on their aims and hopes for the future.

PMID- 29584522
TI  - Physical Activity and Disability: An Analysis on How Activity Might Lower Medical
      Expenditures.
AB  - BACKGROUND: This study evaluated the effect of increased physical activity on
      annual medical expenditures among people with disability, as well as people
      without disability. METHODS: We performed a cross-sectional study with linked
      national survey data from 2004 to 2013 Medical Expenditure Panel Survey and from
      2002 to 2012 National Health Interview Study. We investigated the effect of
      physical activity on the annual medical expenditures in 2013 US dollars, among
      people with and without disability who were 18- to 64-year-old adults. RESULTS:
      For people with disability, we found a statistically significant effect (P < .05)
      of physical activity on annual medical expenditures. Among people without
      disability, being inactive was associated with higher medical expenditures,
      compared with being sufficiently active. In our counterfactual analysis, among
      inactive people with disability, increasing activity to even a low level of
      activity could potentially save on average $2150.06 (95% confidence interval,
      770.39 to 3529.72) annual medical costs. CONCLUSIONS: This analysis provides
      evidence that when an individual with a disability moves from inactive to active,
      the savings in medical expenditures are substantially larger than the savings for
      an individual without a disability ($2564.33 vs $393.34). Despite the challenge
      of participating in physical activity for people with disability, completing
      "some" activity may have large public health implications.

PMID- 29584523
TI  - Brain-Behavior Mechanisms for the Transfer of Neuromuscular Training Adaptions to
      Simulated Sport: Initial Findings From the Train the Brain Project.
AB  - CONTEXT: A limiting factor for reducing anterior cruciate ligament injury risk is
      ensuring that the movement adaptions made during the prevention program transfer
      to sport-specific activity. Virtual reality provides a mechanism to assess
      transferability, and neuroimaging provides a means to assay the neural processes
      allowing for such skill transfer. OBJECTIVE: To determine the neural mechanisms
      for injury risk-reducing biomechanics transfer to sport after anterior cruciate
      ligament injury prevention training. DESIGN: Cohort study. SETTING: Research
      laboratory. PARTICIPANTS: Four healthy high school soccer athletes.
      INTERVENTIONS: Participants completed augmented neuromuscular training utilizing
      real-time visual feedback. An unloaded knee extension task and a loaded leg press
      task were completed with neuroimaging before and after training. A virtual
      reality soccer-specific landing task was also competed following training to
      assess transfer of movement mechanics. MAIN OUTCOME MEASURES: Landing mechanics
      during the virtual reality soccer task and blood oxygen level-dependent signal
      change during neuroimaging. RESULTS: Increased motor planning, sensory and visual
      region activity during unloaded knee extension and decreased motor cortex
      activity during loaded leg press were highly correlated with improvements in
      landing mechanics (decreased hip adduction and knee rotation). CONCLUSION:
      Changes in brain activity may underlie adaptation and transfer of injury risk
      reducing movement mechanics to sport activity. Clinicians may be able to target
      these specific brain processes with adjunctive therapy to facilitate intervention
      improvements transferring to sport.

PMID- 29584524
TI  - Impact of Neonatal Intensive Care Unit Admission on Bacterial Colonization of
      Donated Human Milk.
AB  - BACKGROUND: Unpasteurized human donor milk typically contains a variety of
      bacteria. The impact of neonatal intensive care unit (NICU) admission of the
      donor's infant and duration of lactation on bacterial contamination of human milk
      is unknown. Research aim: This study aimed (a) to describe the
      frequency/concentration of skin commensal bacteria and pathogens in unpasteurized
      human donor milk and (b) to assess the impact of NICU admission and (c) the
      duration of milk expression on bacterial colonization of donated milk. METHODS:
      The authors conducted a retrospective cohort study of human milk donated to the
      Rogers Hixon Ontario Human Milk Bank from January 2013 to June 2014. Milk samples
      from each donor were cultured every 2 weeks. RESULTS: The study included 198
      donor mothers, of whom 63 had infants admitted to the NICU. Of 1,289 cultures
      obtained, 1,031 (80%) had detectable bacterial growth and 363 (28%) yielded
      bacterial growth in excess of 107 cfu/L, a local threshold for allowable bacteria
      prior to pasteurization. The mean (standard deviation) donation period per donor
      was 13.0 (7.5) weeks. Milk from mothers with NICU exposure had significantly
      higher concentrations of commensals, but not pathogens, at every time period
      compared with other mothers. For every 1-month increase in donation from all
      donors, the odds ratio of presence of any commensal in milk increased by 1.13
      (95% confidence interval [1.03, 1.23]) and any pathogen by 1.31 (95% confidence
      interval [1.20, 1.43]). CONCLUSION: Commensal bacteria were more abundant in
      donor milk expressed from mothers exposed to neonatal intensive care. Bacterial
      contamination increased over the milk donation period.

PMID- 29584525
TI  - Differences in the Modified Disablement in the Physically Active Scale in Those
      With and Without Chronic Ankle Instability.
AB  - CONTEXT: The modified disablement in the physically active scale (mDPA) has
      become a commonly utilized patient-reported outcome instrument (PRO) for
      physically active patients. However, the factor structure of this instrument has
      not been verified in individuals with chronic ankle instability (CAI).
      Furthermore, additional evidence examining the mDPA in individuals with CAI is
      warranted. OBJECTIVE: The purpose of this study was to verify the factor
      structure of the modified Disablement in the Physically Active Scale (mDPA) and
      compare the physical summary component (PSC) and mental summary component (MSC)
      in those with and without CAI. DESIGN: Cross-sectional Setting: Laboratory
      Participants: A total of 118 CAI and 81 healthy controls from a convenience
      sample participated. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: All
      subjects completed the 16-item mDPA which included the PSC and MSC; higher scores
      represent greater disablement. To examine the model fit of the mDPA, a single
      factor and two-factor (PSC and MSC) structure were tested. Group differences were
      examined with independent t-tests (p<=0.05) and Hedges' g effect sizes (ES).
      RESULTS: Model fit indices showed the two-factor structure to possesses adequate
      fit to the data, chi2(101)=275.58, p<0.001, CFI=0.91, RMSEA=0.09 (95%CI=0.08,
      0.11), SRMR=0.06. All items loaded significantly and in expected directions on
      respective subscales (lambda range=0.59-0.87, all p<0.001). The CAI group
      reported greater disablement as indicated from PSC (CAI:11.45+/-8.30,
      Healthy:0.62+/-1.80, p<0.001, ES=1.67(95%CI=1.33,1.99)) and MSC (CAI:1.75+/-2.58,
      Healthy:0.58+/-1.46, p<0.001, ES=0.53(95%CI=0.24,0.82)) scores. CONCLUSION: The
      two-factor structure of the mDPA was verified. Individuals with CAI reported
      greater disablement on the PSC compared to healthy controls. The moderate ES on
      the MSC between groups warrants further investigation. Overall, these results
      indicate the mDPA is a generic PRO that can be utilized with individuals who have
      CAI.

PMID- 29584526
TI  - Corrected QT interval prolongation during anesthetic induction for laryngeal mask
      airway insertion with or without cisatracurium.
AB  - Objective This study was performed to observe the occurrence of corrected QT
      (QTc) interval prolongation during anesthetic induction for laryngeal mask airway
      insertion and the effects of cisatracurium administration on the QTc interval.
      Methods Eighty-eight patients were assigned to two groups: the cisatracurium
      administration group (n = 45) and non-cisatracurium administration group (n =
      43). The QTc interval was continuously recorded by a 12-lead Holter
      electrocardiogram beginning in the hospital ward and continuing until after
      anesthetic induction. Results In the cisatracurium administration group, the QTc
      interval significantly increased from 417.9 +/- 27.9 to 451.6 +/- 32.5 ms after
      arrival in the operating room and significantly decreased to 432.4 +/- 32.5 ms
      after a 15-minute rest; it significantly increased to 459.7 +/- 23.8 ms again
      after propofol and fentanyl injection. However, the QTc interval decreased after
      cisatracurium injection. In the non-cisatracurium administration group, the QTc
      interval initially showed changes similar to those in the cisatracurium group
      until fentanyl and propofol were injected. Conclusions The QTc interval was
      significantly prolonged on arrival in the operating room and after propofol and
      fentanyl injection. The QTc interval did not significantly change by laryngeal
      mask airway insertion regardless of the administration of cisatracurium.

PMID- 29584527
TI  - Teacher-Level Factors, Classroom Physical Activity Opportunities, and Children's
      Physical Activity Levels.
AB  - BACKGROUND: Classroom-based physical activity (CBPA) breaks are a cost-effective
      strategy to promote physical activity (PA) at school. Despite teachers' critical
      roles in sustained implementation of CBPA breaks, few studies examined the
      association of teacher-level factors with student PA levels, and none focused on
      rural schools. METHODS: We monitored children's PA levels over 4 consecutive
      school days at 6 rural Oregon elementary schools with Walk4Life pedometers.
      During the same week, teachers recorded all student PA opportunities (recess, PE,
      and CBPA breaks) and answered a 26-item questionnaire about factors influencing
      their use of CBPA breaks. Mixed-effects models were used to associate teacher
      level factors and PA opportunities with children's moderate to vigorous PA (MVPA;
      in minutes per day), controlling for child-level covariates. RESULTS: When
      teachers valued PA, students accumulated more MVPA (1.07 min/d; P < .01) than
      students of teachers reporting low PA value. Students did more MVPA (1 min/d; P <
      .001) when teachers agreed the school operating conditions posed barriers to
      providing PA than when teachers disagreed that barriers existed. PE classes
      contributed significantly to student's PA levels. CONCLUSION: Provision of PE,
      increasing teacher value for PA, and further investigation of how teacher-level
      factors relate to students' MVPA levels during CBPA breaks at rural elementary
      schools are warranted.

PMID- 29584528
TI  - The Cortisol Awakening Response: Association With Training Load in Endurance
      Runners.
AB  - : The cortisol awakening response (CAR) is commonly used as a marker of
      psychological stress; however, it is unknown whether CAR is affected by regular
      physical-exercise-induced stress. PURPOSE: To assess the relationship between
      training load and CAR. METHODS: Recreational endurance athletes were recruited
      from local running clubs. Subjects (n = 15) completed training logs for 2 wk,
      with various training loads, including psychometric analysis (Recovery-Stress
      Questionnaire for Athletes). Subjects provided saliva samples each day
      immediately after waking and 30 min postwaking. Samples were analyzed for
      cortisol concentration via enzyme-linked immunosorbent assay and subsequently
      were analyzed for CAR and CAR%. Daily training load was calculated and analyzed
      as training impulse. Simple linear regression was used to assess the relationship
      between CAR and training impulse. RESULTS: CAR (r2 = .352, P = .025) and CAR% (r2
      = .373, P = .012) both showed a significant negative relationship with training
      load. CONCLUSIONS: These results suggest that CAR is affected by regular exercise
      training loads in recreational athletes. It is recommended that future CAR
      research control for fitness level and exercise training load in physically
      active populations.

PMID- 29584529
TI  - Characterization and Pharmacokinetics of Triamcinolone Acetonide-Loaded Liposomes
      Topical Formulations for Vitreoretinal Drug Delivery.
AB  - PURPOSE: To achieve a safer alternative to intravitreal injection of
      corticosteroids, we developed and characterized triamcinolone acetonide-loaded
      liposomes formulations (TA-LFs) to be used topically for vitreoretinal drug
      delivery. METHODS: Four different 0.2% TA-LFs (TA-LF1 to TA-LF4) were generated
      and submitted to physicochemical characterization. Posteriorly, an ex vivo
      diffusion assay was performed using rabbit corneas as membranes. Finally,
      concentrations of triamcinolone acetonide (TA) were determined by high
      performance liquid chromatography in ocular tissues from New Zealand white
      rabbits after multiple topical doses of TA-LF2 (6 times per day, 14 days). In
      addition, toxicity and tolerability of TA-LF2 was evaluated by cell viability
      assay and eye examination of study animals, respectively. RESULTS: TA-LF2 was the
      most stable formulation maintaining a stable hidrogenion potential (pH) at 30 and
      40 degrees C and even improving encapsulation with higher temperature. TA-LF2 and
      TA-LF3 presented the best diffusion performance in vitro reaching the highest TA
      concentrations after 8 h of follow-up. In vivo diffusion and pharmacokinetics
      analysis showed that concentrations of TA in retina and vitreous reached the
      highest peak at 12 h after topical administration of TA-LF2 (252.10 +/- 90.00
      ng/g and 32.6 +/- 10.27 ng/g, respectively) and subsequently decline to 24.0 +/-
      11.72 ng/g and 19.5 +/- 13.14 ng/g, respectively, at 14 days of follow-up.
      Finally, cell viability was unaffected by TA-LF2, and no increase in intraocular
      pressure nor ocular alterations were observed after topical administration of
      this formulation in rabbits. CONCLUSION: TA-loaded liposomes, administered
      topically, can deliver TA in the vitreous cavity and reach the retina
      efficiently.

PMID- 29584530
TI  - Monitoring Training Load, Recovery, and Performance of Brazilian Professional
      Volleyball Players During a Season.
AB  - PURPOSE: To describe and analyze the distribution of internal training load
      (ITL), recovery, and physical performance of professional volleyball players
      throughout 1 season. METHODS: Fifteen male professional Brazilian volleyball
      players participated in this study. The session rating of perceived exertion (s
      RPE) and Total Quality Recovery (TQR) score were collected daily for 36 wk. s-RPE
      was collected after each training session, and TQR, before the first session of
      the day. The sum of the ITL of each session during the week, training monotony,
      strain, acute?chronic workload ratio, match difficulty score, and average of the
      TQR scores were recorded for the analysis. In addition, the athletes performed
      countermovement-jump (CMJ) tests with and without the use of the arms 4 times
      over the season. RESULTS: The season mean weekly ITL was 3733 (1228) AU and the
      TQR was 15.02 (0.71). The ITL and recovery demonstrated undulating dynamics over
      the 36 wk, with higher weekly ITL in the preparatory periods (F = 50.32; P <
      .001) and worse recovery during the main competition (F = 6.47; P = .004).
      Negative correlations were found between TQR and ITL variables (P < .05). There
      was improvement and maintenance in CMJ tests without (F = 11.88; P < .001) and
      with (F = 16.02; P < .001) the use of the arms after the preparatory periods.
      CONCLUSIONS: The ITL variables, recovery, and physical performance changed
      significantly throughout a professional volleyball season. Despite the decrease
      in ITL during the main competitive period, the correct distribution of weekly ITL
      seems to be very important to guarantee the best recovery of athletes.

PMID- 29584531
TI  - Historical Methods.

PMID- 29584532
TI  - Validation of the French Version of Conners' Parent Rating Scale-Revised, Short
      Version (CPRS-R:S): Scale Measurement Invariance by Sex and Age.
AB  - OBJECTIVE: ADHD is one of the most frequent neurodevelopmental disorders. In
      addition to clinical assessment, its diagnosis requires the use of validated and
      reliable behavior questionnaires such as the Conners' Parent Rating Scale
      Revised: Short Form (CPRS-R:S). Though various French versions of the CPRS-R:S
      have been already put to use in clinical practice and research, only a few have
      undergone a stringent validation process. After a previous validation of the
      factorial structure of Lausanne French version, we sought here for the analysis
      of its invariance across sex and age. METHOD: This validation step was carried
      out in a rather homogeneous French population of 365 boys and 374 girls from a
      single school. Two-age classes were considered: children (boys and girls) aged 9
      to 11 years ( n = 258) and adolescents aged 12 to 15 years ( n = 481). RESULTS:
      Regarding age, dimension Oppositional showed a strong invariance whereas
      dimensions Hyperactivity and Cognitive problems/Inattention showed a partially
      strong invariance. Regarding sex, dimensions Oppositional and Hyperactivity
      showed a partially strong invariance whereas dimension Cognitive
      problems/Inattention showed a partially weak invariance. The distribution of the
      CPRS-R:S scores is given by sex and age class. CONCLUSION: The Lausanne French
      version of the CPRS-R:S, already validated regarding its factorial structure,
      internal consistency, and reliability, is here validated regarding its invariance
      across sex and age. Caution should be taken in using dimension Cognitive
      problems/Inattention in comparisons between boys and girls.

PMID- 29584533
TI  - Rehabilitation Exercises for the Gluteus Minimus Muscle Segments - An
      Electromyography Study.
AB  - CONTEXT: The gluteus minimus (GMin) muscle consists of two uniquely oriented
      segments that have potential for independent function, and have different
      responses to pathology and ageing. For healthy, young adults it is unknown which
      rehabilitation exercises specifically target the individual segments. OBJECTIVE:
      To quantify segmental GMin activity for six common lower limb rehabilitation
      exercises in healthy young adults, and determine if significant differences exist
      in segmental activity levels between the exercises. METHOD: Six common lower limb
      rehabilitation exercises were performed by ten healthy young adults with fine
      wire electromyography (EMG) electrodes inserted into the anterior and posterior
      segments of the GMin muscle. MAIN OUTCOME MEASURES: EMG signals were recorded and
      median normalised exercise activity levels were reported and compared for each
      GMin segment across the six exercises. RESULTS: High activity levels were
      generated in the anterior segment by the resisted hip abduction-extension
      exercise (51% maximum voluntary isometric contraction (MVIC)), while for the
      posterior segment high activity levels were produced by the single leg bridge
      (49% MVIC), the side lie hip abduction (43% MVIC), the resisted hip abduction
      extension exercise (43% MVIC), and the single leg squat (40% MVIC). There were
      significant differences (P < .05) in the median EMG activity levels for the
      anterior GMin segment but not for the posterior GMin segment across some of the
      exercises with large effect sizes. CONCLUSIONS: Targeted rehabilitation exercises
      graded by exercise intensity can be prescribed specifically for the anterior and
      posterior GMin segments to aid in restoration of hip function following injury or
      ageing.

PMID- 29584534
TI  - The pro-inflammatory role of platelets in cancer.
AB  - Thrombosis is a frequent issue in cancer patients. Tumor-induced platelet
      activation and coagulation does not only constitute a significant risk for
      thrombosis, but also contribute to tumor progression by promoting critical
      processes such as angiogenesis and metastasis. In addition to their role in
      hemostasis, platelets are increasingly recognized as regulators of inflammation.
      By modulating the immune system, platelets regulate several aspects of cancer
      associated pathology. Platelets influence the inflammatory response in cancer by
      affecting the activation status of the endothelium and by recruiting leukocytes
      to primary and metastatic tumor sites, as well as to distant organs unaffected by
      tumor growth. Furthermore, platelets participate in the formation of neutrophil
      extracellular traps, which can promote metastasis, thrombosis, and contribute to
      organ failure. In this review, we discuss the role of platelets as coordinators
      of the immune system during malignant disease and the potential of targeting
      platelets to prevent cancer-associated pathology.

PMID- 29584535
TI  - Intracranial hypertension related to cerebral venous thrombosis; and acute
      ischemic stroke with micro-infarcts associated with IgG4-related disease.
AB  - IgG4-related systemic disease (IgG4-RD) is characterized by an inflammatory
      reaction rich in IgG4-positive plasma cells, affecting multiple organs. This
      report describes a case who was diagnosed with IgG4-RD, having cerebral venous
      thrombosis and a subsequent acute ischemic stroke of undetermined cause. A 47
      year-old woman presented with headache, visual disturbance and eyelid swelling
      and two years later she was admitted with acute attacks of mild left lower limb
      sensory-motor monoparesis. Indirect immunohistochemistry assay showed elevated
      level of IgG4, labeling neurons of the central nervous system, suggesting an
      immunological process possibly affecting vascular structures. Our experience
      suggests that IgG4-RD may be considered in patients with ischemic stroke and
      cerebral venous system involvement.

PMID- 29584536
TI  - Examining Practice and Learning Effects with Serial Administration of the
      Clinical Reaction Time Test in Healthy Young Athletes.
AB  - CONTEXT: The Clinical Reaction Time (RTclin) test has been recommended as a valid
      test for assessing concussion and determining recovery of reaction time function
      following concussion. However, it is unknown whether repeat assessment, as is
      used in post-concussion testing, is affected by learning or practice phenomena.
      OBJECTIVE: To determine if a practice or learning effect is present with serial
      administration of the RTclin test. DESIGN: Randomized control trial. SETTING:
      University athletic training clinics. PARTICIPANTS: One hundred and twelve
      healthy collegiate athletes (age = 19.46y +/- 1.34). INTERVENTION(S): The control
      group completed the RTclin test on Days 1 and 60. The experimental group
      completed the RTclin test on Days 1, 2, 3, 7 and 60. MAIN OUTCOME MEASURE(S):
      Reaction time as measured with the RTclin test. RESULTS: The difference in RTclin
      test performance from Day 1 to Day 60 was not significant (Mean Change = -2.77 +/
      14.46ms, P = .421, 95%CIs: -6.40, .862) between groups. The experimental group
      experienced significant improvement (lambda = .784, F4,49 = 3.365, P= .016, eta2=
      .216, power =.81) with acute repeat testing. However, post-hoc analysis did not
      reveal a significant difference between scores during the 5 test periods.
      CONCLUSIONS: The results suggest serial administration of the RTclin test does
      not produce a practice or learning effect. Clinicians, however, should be
      cautious as the results do provide evidence patients may demonstrate improved
      scores when testing occurs on repetitive days after initial exposure to the test.

PMID- 29584537
TI  - Early mortality in elderly patients undergoing treatment for multiple myeloma in
      real-world practice.
AB  - Objectives This study was performed to analyze the risk factors for early
      mortality (EM) in elderly patients undergoing treatment for multiple myeloma (MM)
      in real-world clinical practice. Methods Retrospective data from 108 elderly
      patients who were newly diagnosed with MM from January 2007 to July 2015 were
      analyzed in a single hematology center. EM was defined as death of any cause
      within 12 months after diagnosis. A multivariate regression model was used to
      evaluate EM. Results EM occurred in 16 (14.8%) elderly patients with newly
      diagnosed MM. The most common cause of death was infection (10/16, 62.5%). In the
      multivariate analysis, only an age of >=75 years, International Staging System
      (ISS) stage III disease, and high lactate dehydrogenase concentration were
      significantly and independently associated with EM. Conclusion Our results
      suggest that infection is the leading cause of EM in elderly patients with MM. An
      age of >=75 years, ISS stage III disease, and a high lactate dehydrogenase
      concentration are significant predictors of EM. We should further target this
      higher-risk patient population to define personalized therapy with which to
      improve outcomes.

PMID- 29584538
TI  - Reducing Fear of Reinjury and Pain Perception Among Athletes with First Time
      Anterior Cruciate Ligament Reconstructions by Implementing Imagery Training.
AB  - CLINICAL SCENARIO: Injuries are an inevitable part of competitive sports as well
      a recreational activities. Research shows that one of the most common
      musculoskeletal complaints that accounts for approximately 48 out of 1,000
      patients are knee related injuries.1 As noted, approximately nine percent of
      these knee complaints are related to anterior cruciate ligament (ACL) injuries.2,
      3 The ACL is commonly injured in contact sports via a non-contact action such as
      planting, cutting, landing on a hyperextended knee, or pivoting and sudden
      deceleration.4 Typically, athletes report feeling immediate pain, hearing a pop
      and resulting in progressive knee swelling; as well as difficulty ambulating. The
      ACL is one of the major ligaments that provides stability to the knee joint by
      preventing anterior translation of the femur in the closed kinetic chain.5
      Therefore, most of the time, a ruptured ACL results in reconstructive surgery
      aimed at repairing the ligament. Athletes will often choose reconstructive
      surgery in efforts to return to physical activity. A major outcome measure that
      assesses the success of an ACL reconstructive surgery is the ability to return to
      sports or recreational activity.6 While surgery is effective at repairing the
      ruptured ligament and restoring ligamentous function, for the most part, the
      percentage of athletes that return to a competitive level of physical activity is
      only 44%.4 Of these 44% that report not returning to pre-injury activity, 24%
      report that the main factors preventing their return is fear or reinjury and
      pain.4, 7 The inability to return to previous level of activity can be stressful
      and mentally frustrating for athletes. Taking into consideration how the
      psychological aspects of the injury affect an athlete's sports performance, it is
      crucial to address psychological factors during physical rehabilitation for an
      athlete to rebuild confidence and overcome fear of reinjury. Currently, most
      physiotherapy and rehabilitation research has primarily focused on the physical
      treatment without focus on the psychological aspects of recovery following an
      injury.5, 7 The use of imagery as a psychological interventions has been
      suggested to be effective at reducing anxiety, tension and pain while promoting
      and encouraging healing after an injury. Imagery is defined as a process of
      performing a skill in one's mind using the senses (touch, feel, smell, vision,
      etc.,) without any overt actions.8 Incorporating a therapeutic intervention that
      targets the psychological effects on an athletes' ability to return to sport is
      necessary to assure that the patient is both physically and mentally prepared to
      return to activity. Therefore, the purpose of the critically appraised topic
      (CAT) was to determine if imagery training in combination with standard physical
      therapy is a suitable option to reduce the fear of reinjury and pain perception
      among first time ACL reconstruction patients.

PMID- 29584539
TI  - Effectiveness of the I2AO2 interdisciplinary programme led by nurses on metabolic
      syndrome and cardiovascular risk: a randomized, controlled trial.
AB  - Objective To evaluate the effectiveness of an interdisciplinary programme led by
      nurses in relation to metabolic syndrome (MS) and cardiovascular risk (CVR).
      Methods This randomized, controlled, clinical trial included 74 patients
      diagnosed with MS (experimental group [EG], n = 37; control group [CG], n = 37).
      The intervention consisted of a 12-month interdisciplinary programme (pre-test, 6
      months of intervention, 12 months of intervention, and 1-year follow-up post
      intervention) coordinated by nursing. Results We found a progressive and
      significant reduction for all clinical, biochemical, and anthropometric
      parameters analysed at different time points. In the EG, remission of MS by 48.1%
      in the short term was observed (83.8% in the medium term) and maintained at 1
      year post-intervention. In the CG, the prevalence of MS increased by 2.7% from
      the initial evaluation to study completion. A similar trend was observed for CVR.
      In the EG, 100% of subjects had a moderate-low risk of CVR at 1 year post
      intervention, whereas the CG had CVR in all categories. Conclusion An
      interdisciplinary, nurse-led programme improves participants' metabolic and
      cardiovascular health, while maintaining long-term effects. Our findings suggest
      an important role of the professional nurse as a nexus between the patient,
      different professionals, and the community.

PMID- 29584540
TI  - Anterior versus posterior surgical approach for lumbosacral tuberculosis.
AB  - Objective To compare two different approaches for the treatment of lumbosacral
      tuberculosis. Patients and Methods In total, 115 patients who were surgically
      treated in our department from July 2010 to July 2014 were included in this
      retrospective study. They were divided into the anterior and posterior approach
      groups. Intraoperative hemorrhage; the surgery time; the Cobb angle
      preoperatively, postoperatively, and at the follow-up visit (2 years
      postoperatively); visual analog scale (VAS) pain scores before and after surgery;
      and Oswestry Disability Index (ODI) scores before and after surgery were compared
      between the two groups. Results The Cobb angle and VAS and ODI scores were
      significantly improved in both groups after surgery. Significant differences were
      found in the operation time, intraoperative hemorrhage, Cobb angle correction,
      and loss of correction at the last follow-up. No significant differences were
      found in the VAS and ODI scores between the groups. Conclusions The posterior
      approach is superior to the anterior approach with respect to the surgery time,
      intraoperative hemorrhage, and Cobb angle postoperatively and at the last follow
      up. When both approaches can be carried out for a patient with lumbosacral
      tuberculosis, the posterior approach should be favored over the anterior
      approach.

PMID- 29584541
TI  - Approximate confidence intervals for the likelihood ratios of a binary diagnostic
      test in the presence of partial disease verification.
AB  - The classic parameters used to assess the accuracy of a binary diagnostic test
      (BDT) are sensitivity and specificity. Other parameters used to describe the
      performance of a BDT are likelihood ratios (LRs). The LRs depend on the
      sensitivity and the specificity of the diagnostic test, and they reflect how much
      greater the probability of a positive or negative diagnostic test result for
      individuals with the disease than that for the individuals without the disease.
      In this study, several confidence intervals are studied for the LRs of a BDT in
      the presence of missing data. Two confidence intervals were studied through the
      method of maximum likelihood and seven confidence intervals were studied by
      applying the multiple imputation by chained equations method. A program in R
      software has been written that allows us to solve the estimation problem posed.
      The results obtained have been applied to the two real examples.

PMID- 29584542
TI  - Toward Decentralized Agrigenomic Surveillance? A Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism Approach for Adaptable and Rapid
      Detection of User-Defined Fungal Pathogens in Potato Crops.
AB  - Agrigenomics is one of the emerging focus areas for omics sciences. Yet,
      agrigenomics differs from medical omics applications such as pharmacogenomics and
      precision medicine, by virtue of vastly distributed geography of applications at
      the intersection of agriculture, nutrition, and genomics research streams.
      Crucially, agrigenomics can address diagnostics and safety surveillance needs in
      remote and rural farming communities or decentralized food, crop, and
      environmental monitoring programs for prompt, selective, and differential
      identification of pathogens. A case in point is the potato crop that serves as a
      fundamental nutritional source worldwide. Decentralized potato crop and plant
      protection facilities are pivotal to minimize unnecessary, preemptive use of
      broad-spectrum fungicides, thus helping to curtail the costs, environmental
      burden, and the development of resistance in opportunistic human pathogenic
      fungi. We report here a polymerase chain reaction-restriction fragment length
      polymorphism approach that is sensitive and adaptable in detection and broad
      identification of fungal pathogens in potato crops, with a view to future
      decentralized agrigenomic surveillance programs. Notably, the fingerprinting
      patterns obtained by the method fully differentiated 12 fungal species examined
      in silico, with 10 of them also tested in vitro. The method can be scaled up
      through improvements in electrophoresis and enzyme panel for adaption to other
      crops and/or pathogens. We suggest that decentralized and integrated
      agrosurveillance programs and translational agrigenomic programs can inform
      future innovations in multidomain biosecurity, particularly across omics
      applications from agriculture and nutrition to clinical medicine and
      environmental biosafety.

PMID- 29584543
TI  - Distinguishing Molecular Features of Allergic Fungal Rhinosinusitis.
AB  - Objective Allergic fungal rhinosinusitis (AFRS) is a clinical subtype of chronic
      rhinosinusitis with nasal polyps (CRSwNP), characterized by eosinophilic mucin,
      evidence of fungal elements within the mucin, fungal-specific type I
      hypersensitivity, and characteristic computed tomography findings. It remains
      controversial whether AFRS represents a disease with a unique pathophysiology
      from chronic rhinosinusitis or is merely a severe form of CRSwNP. The goal of
      this study was to identify molecular features unique to AFRS. Study Design Cross
      sectional case-control. Setting Single academic tertiary referral institution.
      Subjects and Methods Subjects included 86 patients undergoing endoscopic sinus
      surgery: CRSwNP (n = 34), AFRS (n = 37), and healthy controls (n = 15). Pathway
      and correlation analyses were performed with whole-genome microarray data for
      study patients undergoing surgery for recalcitrant chronic rhinosinusitis. Our
      findings were confirmed with quantitative polymerase chain reaction and
      immunohistochemical studies. Results AFRS was uniquely characterized by a
      pronounced association with adaptive T helper 2-associated immune gene
      expression. AFRS exhibited altered expression of proteins associated with
      secretory salivary peptides-namely, histatin, a peptide with known antifungal
      activity in the oral cavity. Furthermore, the expression of histatins correlated
      negatively with that of type 2 inflammatory mediators. We confirm the decreased
      expression of histatins in AFRS when compared with CRSwNP by quantitative
      polymerase chain reaction and localized its expression to a submucosal cell
      population. Conclusion There exist clear molecular profiles that distinguish AFRS
      from CRSwNP. This divergence translates into an altered ability to control fungal
      growth and may in part explain some of the phenotypical differences between
      CRSwNP and AFRS.

PMID- 29584544
TI  - Drivers of treatment patterns in patients with chronic lymphocytic leukemia
      stopping ibrutinib or idelalisib therapies.
AB  - Novel therapies including kinase inhibitors (KI) have led to high and durable
      response in patients with chronic lymphocytic leukemia (CLL), however, some
      patients stop therapy. This study evaluates reasons for treatment changes among
      CLL patients who stopped KI in real-world practice. Sixty-nine US
      oncologists/hematologists provided patient-level data abstracted from charts of
      CLL adult patients who initiated a KI and later (1) switched to another anti
      neoplastic regimen (Switched cohort), (2) discontinued the KI and remained
      untreated (Discontinued cohort), or (3) restarted the same KI after an
      interruption of >=60 days (Restarted cohort). Demographics, clinical/treatment
      characteristics, and reasons for stopping, restarting, and switching the KI
      therapy were described. In the Switched cohort, reasons for stopping included
      disease progression (72.5%), low/no disease activity (3.9%), adverse event [AE]/
      intolerance/comorbidity (15.7%), and planned cellular therapies (7.9%). In the
      Discontinued cohort, approximately half (46.0%) of patients stopped KI therapy
      because they were terminally ill/died, or were moved to best supportive care -
      these patients were older, had more severe disease, and high comorbidity burden.
      The other half (54.0% of patients) stopped due to low/no disease activity
      (24.0%), AEs/toxicity (12.0%), or patient-requested drug holiday (18.0%). In the
      Restarted cohort, the most common reasons for stopping KIs were patient request
      (37.3%), AEs/intolerance (31.4%), and economic reasons (10%). Patients restarted
      when disease progressed (60.8%) or when they recovered from the AE (33%). Reasons
      for KI stop and subsequent treatment patterns were varied and multifactorial,
      suggesting heterogeneous disease management and a need for more evidence around
      supporting strategies and physician education.

PMID- 29584545
TI  - Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal
      Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2
      Consortium (NCI-9742).
AB  - Purpose This multinational study evaluated the antitumor activity of nivolumab in
      nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were
      investigated in an exploratory analysis. Patients and Methods Patients with
      multiply pretreated recurrent or metastatic NPC were treated with nivolumab until
      disease progression. The primary end point was objective response rate (ORR) and
      secondary end points included survival and toxicity. The expression of programmed
      death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors
      and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and
      survival. Results A total of 44 patients were evaluated and the overall ORR was
      20.5% (complete response, n = 1; partial response, n = 8). Nine patients received
      nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95%
      CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3%
      (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and
      the biomarkers; however, a descriptive analysis showed that the proportion of
      patients who responded was higher among those with PD-L1 positive tumors (> 1%
      expression) than those with PD-L1-negative tumors. The loss of expression of one
      or both human leukocyte antigen class 1 proteins was associated with better PFS
      than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P =
      .01). There was no association between survival and PD-L1 expression or plasma
      Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab.
      Conclusion Nivolumab has promising activity in NPC and the 1-year overall
      survival rate compares favorably with historic data in similar populations.
      Additional evaluation in a randomized setting is warranted. The biomarker results
      were hypothesis generating and validation in larger cohorts is needed.

PMID- 29584546
TI  - Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of
      Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the
      Multicohort Single-Arm Phase II CheckMate 205 Trial.
AB  - Purpose Genetic alterations causing overexpression of programmed death-1 ligands
      are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed
      death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL
      after autologous hematopoietic cell transplantation (auto-HCT) in initial
      analyses of one of three cohorts from the CheckMate 205 study of nivolumab for
      cHL. Here, we assess safety and efficacy after extended follow-up of all three
      cohorts. Methods This multicenter, single-arm, phase II study enrolled patients
      with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by
      treatment history: brentuximab vedotin (BV)-naive (cohort A), BV received after
      auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All
      patients received nivolumab 3 mg/kg every 2 weeks until disease
      progression/unacceptable toxicity. The primary end point was objective response
      rate per independent radiology review committee. Results Overall, 243 patients
      were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median
      follow-up of 18 months, 40% continued to receive treatment. The objective
      response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort.
      Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3
      months), and median progression-free survival was 14.7 months (95% CI, 11.3 to
      18.5 months). Of 70 patients treated past conventional disease progression, 61%
      of those evaluable had stable or further reduced target tumor burdens. The most
      common grade 3 to 4 drug-related adverse events were lipase increases (5%),
      neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were
      considered treatment related. Conclusion With extended follow-up, responses to
      nivolumab were frequent and durable. Nivolumab seems to be associated with a
      favorable safety profile and long-term benefits across a broad spectrum of
      patients with relapsed/refractory cHL.

PMID- 29584547
TI  - Molecular Characterization and Mortality From Breast Cancer in Men.
AB  - Purpose Limited data exist on the molecular biology, treatment, and outcomes of
      breast cancer in men, and much of our understanding in this area remains largely
      an extrapolation from data in women with breast cancer. Materials and Methods We
      studied men and women with hormone receptor-positive breast cancer and the 21
      gene Breast Recurrence Score (RS) results. Differences in clinical
      characteristics and gene expression were determined, and distribution of RS
      results was correlated with 5-year breast cancer-specific survival (BCSS) and
      overall survival. Results There were 3,806 men and 571,115 women. Men were older
      than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both
      genders, but RS >= 31 was more frequent in men (12.4% v 7.4%; P < .001), as were
      very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was
      higher in men for the estrogen receptor (ER), proliferation, and invasion groups.
      ER was lowest and progesterone receptor was highest in women younger than 50
      years of age, with a progressive increase in ER with age. Men younger than 50
      years of age had slightly lower ER and progesterone receptor compared with older
      men. Survival data were available from SEER for 322 men and 55,842 women. Five
      year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%)
      for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95%
      CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS >= 31
      was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and
      94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall
      survival were lower in men than in women. Conclusion This study reveals some
      distinctive biologic features of breast cancer in men and an important prognostic
      role for RS testing in both men and women.

PMID- 29584548
TI  - Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non
      Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and
      Obinutuzumab Maintenance in the GADOLIN Study.
AB  - Purpose To perform an updated analysis of the randomized phase III GADOLIN trial
      in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with
      obinutuzumab (GA101; G) and bendamustine (B). Patients and Methods Patients with
      histologically documented, rituximab-refractory CD20+ indolent non-Hodgkin
      lymphoma received G 1,000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2 to 6)
      plus B 90 mg/m2/d (days 1 and 2, all cycles) or B 120 mg/m2/d monotherapy.
      Patients who did not experience disease progression with G-B received G
      maintenance (1,000 mg every 2 months) for up to 2 years. The primary end point
      was progression-free survival (PFS). Results Of 413 randomly assigned patients
      (intention-to-treat [ITT]: G-B, n = 204; B monotherapy, n = 209), 335 had
      follicular lymphoma (FL; G-B, n = 164; B monotherapy, n = 171). After a median
      follow-up of 31.8 months, median PFS in ITT patients was 25.8 months (G-B) and
      14.1 months (B monotherapy; hazard ratio [HR], 0.57; 95% CI, 0.44 to 0.73; P <
      .001). Overall survival (OS) also was prolonged (HR, 0.67; 95% CI, 0.47 to 0.96;
      P = .027). PFS and OS benefits were similar in patients with FL. Grade 3 to 5
      adverse events (AEs) were reported by 148 (72.5%) and 133 (65.5%) patients in the
      G-B and B monotherapy arms, respectively, most commonly neutropenia (G-B, 34.8%;
      B monotherapy, 27.1%), thrombocytopenia (10.8% and 15.8%), anemia (7.4% and
      10.8%), and infusion-related reactions (9.3% and 3.4%). Serious AEs occurred in
      89 G-B patients (43.6%) and 75 B monotherapy patients (36.9%); fatal AEs occurred
      in 16 (7.8%) and 13 (6.4%), respectively. Conclusion This updated analysis
      confirms the PFS benefit for G-B shown in the primary analysis. A substantial OS
      benefit also was demonstrated in the ITT population and in patients with FL.
      Toxicity was similar for both treatments.

PMID- 29584549
TI  - Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel
      Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth
      Factor Receptor 2/neu.
AB  - Purpose Uterine serous carcinoma is a rare, aggressive variant of endometrial
      cancer. Trastuzumab is a humanized monoclonal antibody that targets human
      epidermal growth factor receptor 2 (HER2)/neu, a receptor overexpressed in 30% of
      uterine serous carcinoma. This multicenter, randomized phase II trial compared
      carboplatin-paclitaxel with and without trastuzumab in patients with advanced or
      recurrent uterine serous carcinoma who overexpress HER2/neu. Methods Eligible
      patients had primary stage III or IV or recurrent HER2/neu-positive disease.
      Participants were randomly assigned to receive carboplatin-paclitaxel (control
      arm) for six cycles with or without intravenous trastuzumab (experimental arm)
      until progression or unacceptable toxicity. The primary end point was progression
      free survival, which was assessed for differences between treatment arms via one
      sided log-rank tests. Results From August 2011 to March 2017, 61 patients were
      randomly assigned. Forty progression-free survival-related events occurred among
      58 evaluable participants. Among all patients, median progression-free survival
      was 8.0 months (control) versus 12.6 months (experimental; P = .005; hazard ratio
      [HR], 0.44; 90% CI, 0.26 to 0.76). Similarly, median progression-free survival
      was 9.3 (control) versus 17.9 (experimental) months among 41 patients with stage
      III or IV disease undergoing primary treatment ( P = .013; HR, 0.40; 90% CI, 0.20
      to 0.80) and 6.0 (control) versus 9.2 months (experimental), respectively, among
      17 patients with recurrent disease ( P = .003; HR, 0.14; 90% CI, 0.04 to 0.53).
      Toxicity was not different between treatment arms, and no unexpected safety
      signals emerged. Conclusion Addition of trastuzumab to carboplatin-paclitaxel was
      well tolerated and increased progression-free survival. These encouraging results
      deserve further investigation to determine their impact on overall survival in
      patients with advanced or recurrent uterine serous carcinoma who overexpress
      HER2/neu.

PMID- 29584551
TI  - Anthropometrics and Allometry: Beyond Body Mass Index.

PMID- 29584550
TI  - Association of Cardiovascular Risk Factors With Cardiac Events and Survival
      Outcomes Among Patients With Breast Cancer Enrolled in SWOG Clinical Trials.
AB  - Background Cardiovascular disease is the primary cause of death among patients
      with breast cancer. However, the association of cardiovascular-disease risk
      factors (CVD-RFs) with long-term survival and cardiac events is not well studied.
      Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer
      trials from 1999 to 2011. We identified baseline diabetes, hypertension,
      hypercholesterolemia, and coronary artery disease by linking trial records to
      Medicare claims. The primary outcome was overall survival. Patients with both
      baseline and follow-up claims were examined for cardiac events. Cox regression
      was used to assess the association between CVD-RFs and outcomes. Results We
      identified 1,460 participants older than 66 years of age from five trials; 842
      were eligible for survival outcomes analysis. At baseline, median age was 70
      years, and median follow-up was 6 years. Hypertension (73%) and
      hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients
      had one or more CVD-RF. There was no association between any of the individual
      CVD-RFs and overall survival except for hypercholesterolemia, which was
      associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57
      to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of
      death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival
      (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free
      survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between
      baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear
      association between the number of CVD-RFs and cardiac event was observed (HR per
      CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in
      clinical trials, each additional baseline CVD-RF was associated with an increased
      risk of cardiac events and death. Efforts to improve control of modifiable CVD
      RFs are needed, especially among those with multiple risk factors.

PMID- 29584552
TI  - SIRT1 in Colorectal Cancer: A Friend or Foe?

PMID- 29584553
TI  - Ultrathin CAD-CAM Ceramic Occlusal Veneers and Anterior Bilaminar Veneers for the
      Treatment of Moderate Dental Biocorrosion: A 1.5-Year Follow-Up.
AB  - Dental biocorrosion can produce a devastating impact on oral health. The
      restorative phase of the treatment should not cause additional damage of the
      remaining sound tooth structure. Ultrathin occlusal veneers are a conservative
      alternative to traditional onlays and complete crowns for the treatment of severe
      biocorrosive lesions. This strategy is explained in the present case report
      through a full-mouth rehabilitation of a patient with moderate biocorrosion.
      Maxillary anterior teeth were restored using the bilaminar technique (lingual
      direct composite veneers with labial ceramic veneers) and posterior teeth using
      ultrathin CAD-CAM ceramic occlusal veneers. The technical aspects required for
      the implementation of this new restorative design are presented with a special
      emphasis on the control of tooth preparation based on diagnostic wax-up,
      provisionalization, and the use of CAD-CAM technology.

PMID- 29584554
TI  - National Trends in Vestibular Schwannoma Surgery: Influence of Patient
      Characteristics on Outcomes.
AB  - Objective To characterize current vestibular schwannoma (VS) surgery outcomes
      with a nationwide database and identify factors associated with increased
      complications and prolonged hospital course. Study Design Retrospective review
      utilizing the University HealthSystem Consortium national inpatient database.
      Setting US academic health centers. Subjects and Methods Data from patients
      undergoing VS surgery were analyzed over a 3-year time span (October 2012 to
      September 2015). Surgical outcomes, such as length of stay (LOS), complications,
      and mortality, were analyzed on the basis of race, sex, age, and comorbidities
      during the 30-day postoperative period. Results A total of 3697 VS surgical cases
      were identified. The overall mortality rate was 0.38%, and the overall
      complication rate was 5.3%. Advanced age significantly affected intensive care
      unit LOS, mortality, and complications ( P = .04). Comorbidities, including
      hypertension, obesity, and depression, also significantly increased complication
      rates ( P = .02). Sixty-eight patients (1.8%) had a history of irradiation, and
      they had a significantly increased LOS ( P = .03). Conclusion Modern VS surgery
      has a low mortality rate and a relatively low rate of complications. Several
      factors contribute to high complication rates, including age and comorbidities.
      These data will help providers in counseling patients on which treatment course
      might be best suited for them.

PMID- 29584555
TI  - Gut microbiota as a source of novel antimicrobials.
AB  - Bacteria, Archaea, Eukarya and viruses coexist in the human gut, and this
      coexistence is functionally balanced by symbiotic or antagonistic relationships.
      Antagonism is often characterized by the production of antimicrobials against
      other organisms occupying the same environmental niche. Indeed, close co
      evolution in the gut has led to the development of specialized antimicrobials,
      which is attracting increased attention as these may serve as novel alternatives
      to antibiotics and thereby help to address the global problem of antimicrobial
      resistance. The gastrointestinal (GI) tract is especially suitable for finding
      novel antimicrobials due to the vast array of microbes that inhabit it, and a
      considerable number of antimicrobial producers of both wide and narrow spectrum
      have been described. In this review, we summarize some of the antimicrobial
      compounds that are produced by bacteria isolated from the gut environment, with a
      special focus on bacteriocins. We also evaluate the potential therapeutic
      application of these compounds to maintain homeostasis in the gut and the
      biocontrol of pathogenic bacteria.

PMID- 29584556
TI  - A Holistic Theoretical Approach to Intellectual Disability: Going Beyond the Four
      Current Perspectives.
AB  - This article describes a holistic theoretical framework that can be used to
      explain intellectual disability (ID) and organize relevant information into a
      usable roadmap to guide understanding and application. Developing the framework
      involved analyzing the four current perspectives on ID and synthesizing this
      information into a holistic theoretical framework. Practices consistent with the
      framework are described, and examples are provided of how multiple stakeholders
      can apply the framework. The article concludes with a discussion of the
      advantages and implications of a holistic theoretical approach to ID.

PMID- 29584559
TI  - Health Services Use and Costs for Americans With Intellectual and Developmental
      Disabilities: A National Analysis.
AB  - Health services and associated costs for adults with intellectual and
      developmental disabilities (IDD) were nationally profiled and the predictors of
      high expense users statistically modeled. Using linked data from the National
      Health Interview Survey and Medical Expenditure Panel Survey for the years 2002
      through 2011, the study found a mixed pattern of differences in rates of service
      use and costs when compared to the general population depending upon personal
      characteristics, health status, and type of health care service. Prescription
      medication costs were the primary driver of total health care expenditures for
      Americans with IDD. The presence of secondary chronic health conditions and poor
      mental health status were the consistent predictors of high expense users across
      types of health care. Study results are discussed in terms of implications for
      more nuanced evaluations of health care costs and need for recurring surveillance
      of health care for Americans with IDD in the years following passage of the
      Patient Protection and Affordable Care Act.

PMID- 29584560
TI  - Impact of Medicaid Managed Care on Illinois's Acute Health Services Expenditures
      for Adults With Intellectual and Developmental Disabilities.
AB  - States have increasingly transitioned Medicaid enrollees with disabilities from
      fee-for-service (FFS) to Medicaid Managed Care (MMC), intending to reduce state
      Medicaid spending and to provide better access to health services. Yet, previous
      studies on the impact of MMC are limited and findings are inconsistent. We
      analyzed the impact of MMC on costs by tracking Illinois's Medicaid acute health
      services expenditures for adults with intellectual and developmental disabilities
      (IDD) living in the community ( n = 1,216) before and after their transition to
      MMC. Results of the difference-in-differences (DID) regression analysis using an
      inverse propensity score weight (IPW) matched comparison group ( n = 1,134)
      design suggest that there were no significant state Medicaid cost savings in
      transitioning people with IDD from FFS to MMC.

PMID- 29584562
TI  - Identifying the Correlates and Barriers of Future Planning Among Parents of
      Individuals With Intellectual and Developmental Disabilities.
AB  - Although individuals with intellectual and developmental disabilities (IDD) are
      living longer lives, fewer than half of parents of individuals with IDD conduct
      future planning. The correlates and barriers to future planning must be
      identified to develop targeted interventions to facilitate future planning. In
      this study, 388 parents of individuals with IDD responded to a national, web
      based survey. Participants who were older, more educated, attended more parent
      training and support activities, and had children with fewer functional
      abilities, were more likely to engage in future planning. Reported barriers to
      future planning included: (a) lack of available services, (b) financial
      challenges, (c) reluctance of family members, (d) lack of time, (e) the emotional
      nature of future planning, (f) inertia, and (g) a lack of family members to be
      caregivers. Implications for policy, practice, and future research are discussed.

PMID- 29584563
TI  - Adverse Childhood Experiences Among Direct Support Professionals.
AB  - Direct support professionals (DSPs) provide integral support to many individuals
      with intellectual and developmental disabilities (IDD). Yet, individuals' access
      to qualified DSPs is often compromised as organizations struggle to hire and
      retain DSPs. Despite a vast body of research exploring factors associated with
      turnover, adverse childhood experiences (ACEs) among DSPs remain absent from the
      literature. ACEs encompass abuse and familial dysfunction prior to the age of 18
      and, in the general population, have been linked to compromised well-being and
      work-related challenges in adult life. An online survey was conducted to explore
      the prevalence of ACE categories and ACE scores (i.e., the sum of each ACE
      category experienced by a person) among DSPs ( n = 386) working in licensed
      settings. Seventy-five percent of DSPs experienced at least one ACE and 30% had
      an ACE score of four or more. DSPs who identified as female and those who had
      been in their position less than one year had significantly higher ACE scores
      than males and others who had been in their position longer, respectively. In
      comparison with other studies, the four most common ACE categories among DSPs
      (i.e., divorce, emotional abuse, mental illness, and substance abuse) were the
      same, however, DSPs in the present study had a higher average ACE score and
      nearly twice the percentage of persons having an ACE score of four or more. The
      potential implications of ACEs among DSPs, at the intersection of their work with
      individuals with IDD, are discussed.

PMID- 29584564
TI  - Association Between MICA Gene Variants and the Risk of Hepatitis C Virus-Induced
      Hepatocellular Cancer in a Sicilian Population Sample.
AB  - There are currently no biomarkers that predict hepatocellular carcinoma (HCC)
      risk in patients with hepatitis C virus (HCV)-related cirrhosis. We investigated
      the relationships among major histocompatibility complex (MHC) class I chain
      related gene A (MICA) polymorphisms, plasma levels of soluble MICA (sMICA), and
      HCC risk in patients with HCV-related HCC. One hundred fifty-four HCV-related HCC
      patients, 93 HCV-related liver cirrhosis (LC) cases, and 244 healthy controls,
      all sampled from the native Sicilian population, were genotyped using the KASPTM
      single-nucleotide polymorphism genotyping method. The MICA rs2596542 polymorphism
      showed that the G/G genotype was significantly more frequent in HCC than control
      subjects and LC patients (p < 0.005). For MICA rs2596538 polymorphism, the C
      allele and C/C genotype were significantly more frequent in HCC than in controls
      and LC cases (p < 0.005), after controlling for potential confounders. These
      results demonstrate that MICA rs2596542G/G, and particularly the rs2596538C/C
      polymorphism, are associated with the risk of developing HCV-related HCC in a
      Sicilian population sample. Importantly, using a machine learning classifier, we
      found that "age" and either rs2596542 or rs2596538 were important discriminating
      factors for patients with LC and HCC. Finally, sMICA levels significantly
      increased during HCV-related liver disease progression, while a significant
      relationship between both rs2596542 and rs2596538 genotypes and sMICA plasma
      levels was identified in patients with LC and HCC. In summary, the MICA rs2596538
      and rs2596542 variants warrant further research for their clinical validity and
      utility in relationship to the risk of developing HCV-related HCC in independent
      populations.

PMID- 29584565
TI  - Neisseria meningitidis serogroup B carriage by adolescents and young adults
      living in Milan, Italy: Prevalence of strains potentially covered by the
      presently available meningococcal B vaccines.
AB  - Recently, two vaccines against meningococcal serogroup B (MenB) have been
      developed. They are prepared according to the reverse vaccinology approach and
      contain 4 (4CMenB) and 2 (MenB-FHbp) cross-reactive surface proteins. In Italy
      4CMenB vaccine has been included in the official vaccination schedule only
      recently and recommended only for infants and toddlers, whereas MenB-FHbp is not
      licensed. In order to collect information about the present carriage of Neisseria
      meningitidis serogroup B (MenB) in Italian adolescents and to evaluate the
      potential protection offered by the presently available MenB vaccines, 2,560
      otherwise healthy, high school students aged 14-21 years (907 males, 35.4%,
      median age 16.2 years) were enrolled in Milan, Italy. A swab to collect posterior
      pharynx secretions was collected from each subject and meningococcal
      identification, serogrouping, multilocus sequence typing analysis, sequence
      alignments and phylogenetic analysis were performed. A total of 135 (5.3%)
      adolescents were meningococcal carriers. Strains belonging to serogroup B were
      the most common (n = 58; 2.3%), followed by MenY (n = 32; 1.2%), MenC (n = 7;
      0.3%), MenW (n = 6; 0.3%) and MenX (n = 5; 0.2%). The remaining bacteria were not
      capsulated. The identified MenB strains belonged to eleven clonal complexes
      (CCs): ST-162 CC (n = 12; 20.7%), ST-865 CC (n = 12; 20.7%), ST-41/44/Lin.3 CC (n
      = 11; 19.0%), ST-35 CC (n = 6; 10.3%), ST-32/ET-5 CC (n = 4; 6.9%), ST-269 CC (n
      = 3; 5.2%), ST-213 CC (n = 2; 3.4%), ST-198 CC (n = 1; 1.7%), ST-461 CC (n = 1;
      1.7%), ST-549 CC (n = 1; 1.7%), and ST-750 CC (n = 1; 1.7%). This study showed
      that MenB was the most commonly carried meningococcal serogroup found in
      adolescents living in Milan, Italy. The MenB vaccines presently licensed could
      have theoretically induced the production of antibodies effective against the
      greatest part of the identified MenB strains (100% in the case of 4CMenB and 95%
      in case of MenB-FHbp) Monitoring carriage remains essential to evaluate MenB
      circulation, but further studies are necessary to evaluate the effect on carriage
      and the final efficacy of both new MenB vaccines.

PMID- 29584566
TI  - Time, Resident Involvement, and Supply Drive Cost Variability in Septoplasty with
      Turbinate Reduction.
AB  - Objective To determine factors that influence cost variability in septoplasty
      with inferior turbinate reduction. Study Design Case series with chart review.
      Setting Tertiary care hospital and affiliated ambulatory surgical center.
      Subjects and Methods Surgical costs were reviewed for adult patients undergoing
      septoplasty with inferior turbinate reduction between December 2014 and September
      2017. Cases where additional procedures were performed were excluded. Operative
      supply costs, operative time, room time, and resident involvement were
      determined. Contribution of these factors to total costs and variability were
      analyzed. Results The study included 116 patients (mean age, 38 years) and 4
      faculty surgeons. Total cost was primarily driven by operative time (74%), with a
      smaller portion of total cost arising from supplies (26%). Time cost ( P < .0001)
      and supply cost ( P = .006) varied significantly among surgeons. A resident was
      involved in 46.6% of cases. When subanalyzed by resident year, no-resident and
      senior resident (postgraduate years 4 and 5) cases had nearly identical mean
      times, while junior resident (postgraduate years 1-3) cases had mean times and
      operative time costs that were 39% greater ( P < .001). Conclusion For
      septoplasty with inferior turbinate reduction, the greatest driver of cost
      variation was operative time. Resident involvement correlated with increased time
      and cost. Supply costs had a much smaller impact. When subanalyzed by resident
      year, junior resident-involved cases were significantly longer than no-resident
      cases.

PMID- 29584567
TI  - Preliminary clinical application of an aromatase inhibitor and a gonadotropin
      releasing hormone agonist combination for inoperable endometrial cancer patients
      with comorbidities: case report and literature review.
AB  - BACKGROUND: Endometrial cancer (EC) occurs most commonly after menopause. A
      proportion of patients present with advanced age and comorbidities, and become
      ineligible for surgery. The optimal treatment strategy of these patients remains
      a clinical challenge. Aromatase inhibitor (AI) combined with Gonadotropin
      releasing hormone agonist (GnRH-a) possesses profound effect in suppressing the
      estrogen level, has become a valid treatment in the breast cancer. However, the
      combined use of an AI and a GnRH-a in EC has rarely been studied. CASE
      PRESENTATION: Herein, we report the combination of an AI and a GnRH-a in the
      treatment of three patients with advanced age or comorbidities who were
      ineligible for surgery. The disease remained stable for two years in patients who
      received the combination treatment as an initial approach without any adverse
      effects. Moreover, an AI combined with a GnRH-a also effective as salvage
      treatment of recurrent patients. Further, we provide a brief review of the
      literature. CONCLUSION: The combination of an AI and a GnRH-a presents
      satisfactory therapeutic effect and provides an optimal option for inoperable EC
      patients.

PMID- 29584568
TI  - High Prevalence of CTX-M-15-Type Extended-Spectrum beta-Lactamase Among AmpC beta
      Lactamase-Producing Klebsiella pneumoniae Isolates Causing Bacteremia in Korea.
AB  - We investigated the antimicrobial susceptibility, the genotypic distributions of
      extended-spectrum beta-lactamase (ESBL) and AmpC genes, and the molecular
      epidemiology of AmpC-producing Klebsiella pneumoniae (AmpC-KP) isolates causing
      bacteremia. Among 260 K. pneumoniae clinical isolates included in this study,
      plasmid-mediated AmpC beta-lactamases were found in 20.7% (54/260), which
      included DHA-1 (96.3%, 52/54), CMY-2 (3.7%, 2/54), and CMY-10 (1.9%, 1/54). One
      isolate also produced DHA-1 along with CMY-2. Of the 54 AmpC-KP isolates, 31
      isolates (57.4%) showed ESBL positivity. Of these 31 isolates with coproduction
      of ESBL and AmpC beta-lactamases, 25 isolates (80.6%) produced CTX-M-15 in
      addition to DHA-1. Nine isolates (29.0%) were nonsusceptible to imipenem. The
      most prevalent sequence type (ST) was ST11 (n = 31, 57.4%), followed by ST2361 (n
      = 5, 9.3%), which was newly identified in this study, and ST48 (n = 4, 7.4%). K.
      pneumoniae isolates coproducing DHA-1 and CTX-M-15 have emerged and disseminated
      in Korean hospitals, even in blood isolates causing bacteremia. Such infections
      may become a challenge for clinicians because there is a severely restricted
      range of available therapeutic options for these pathogens.

PMID- 29584569
TI  - Setting the stage for the review of the international estimate of short-term
      intake (IESTI) equation.
AB  - In the framework of setting Maximum Residue Limits (MRLs) for pesticides, both
      chronic and acute health risks to consumers arising from the long-term and short
      term dietary exposure to pesticide residues have to be assessed. The current
      internationally harmonized approach for assessing the acute dietary exposure is
      based on deterministic methods for calculating the IESTI (International Estimate
      of Short-Term Intake). Recently, it became apparent that the IESTI approach needs
      a revision in the light of new scientific and political aspects. The main reasons
      that require this review were the lack of an international harmonization of the
      methodology which implies trade barriers as well as difficulties in risk
      communication concerning the public trust in regulatory systems. The most recent
      milestone in the scientific debate on a possible revision of the IESTI equation
      was an international scientific workshop held in Geneva in September 2015. The
      main objectives of this meeting were the re-evaluation, and where possible, the
      international harmonization of the input parameters for the IESTI equations as
      well as the equations themselves. The main recommendations from the workshop were
      (i) to replace the highest residue and supervised trials median residue with the
      maximum residue limit (MRL), (ii) to use a standard variability factor of three,
      (iii) to derive the P97.5 large portion value from the distribution of
      consumption values of dietary surveys expressed as kg food/kg bw/d, and (iv) to
      remove the commodity unit weight from the equations. In addition, the application
      of conversion factors and processing factors was addressed. On the initiative of
      the (World Health Organization) WHO Collaborating Centre on Chemical Food Safety
      at the National Institute for Public Health and the Environment (RIVM), the
      Netherlands, an international working group with members from the French Agency
      for Food, Environmental and Occupational Health and Safety, France (ANSES),
      Australian Pesticides and Veterinary Medicines Authority, Australia (APVMA),
      German Federal Institute for Risk Assessment, Germany (BfR), Chemical Regulation
      Division, the United Kingdom (CRD), European Food Safety Authority (EFSA), and
      RIVM, the Netherlands was formed after the IESTI workshop to conduct a
      comprehensive impact assessment of the proposed changes of the IESTI equations.

PMID- 29584570
TI  - Factors affecting the quantitative uncertainty of the estimated short-term
      intake. Part II-Practical examples.
AB  - The effects of the spread of residue concentrations in the samples derived from
      the selected supervised trials and the number of trials were studied on the
      magnitude and uncertainty of the short-term dietary intakes calculated with the
      proposed new procedure (IESTIp) and that one used currently by the FAO (Food and
      Agriculture Organization) and WHO (World Health Organization) Joint meeting on
      Pesticide Residues (JMPR) (IESTIc). The residue data of 10 pesticides were
      obtained from supervised trials conducted on apples and pears. The methods
      described in Part I were used for the calculations of the uncertainty. The
      results indicate that the ratio of IESTIP to IESTIc (phiIESTI) is directly
      proportional to the ratio of the estimated maximum residue level (MRL),
      recommended by the JMPR; to the highest residue (HR) observed in supervised
      trials, and it may have a wide range depending on the particular conditions. The
      phiIESTI becomes greater with the increase of the difference between the mrl or
      maximum residue limit (MRL, established by the Codex Alimentarius Commission,
      CAC) and HR, and becomes smaller if the difference between the large portion (LP)
      and unit mass (U) decreases. The phiIESTI ranged between 2 and 5.1 in the 16
      cases examined indicating that the IESTIp calculation method leads to higher
      intake estimates. The ratio of CVIESTIp and CVIESTIc ranged typically between
      0.62 and 1.71. It rapidly increased up to 12 trials. For a larger number of
      trials, the ratio remained practically constant (1.69-1.71). The processing
      factor (PF) equally affects the MRL and HR values, therefore, it will not
      practically influence the phiIESTI. The uncertainty of the estimated median
      residues depends on the spread and number of values in the residue datasets,
      which affects the uncertainty of the conversion factor (CF) and subsequently the
      uncertainty of the estimated IESTIp. Residue values obtained from minimum nine
      independent trials are required for the correct calculation of the 95% confidence
      intervals of the calculated median residues. The uncertainty of the analytical
      results directly affects the median, HR values and indirectly the calculated mrl
      and the MRL derived from it. Therefore, it should also be considered for the
      calculation of the combined uncertainty of the conversion factors. For the
      correct interpretation of the results of dietary exposure calculations, the upper
      95% confidence limit of the short-term intake should also be considered. However,
      it is not the current practice of regulatory agencies or JMPR.

PMID- 29584571
TI  - Factors affecting the quantitative uncertainty of the estimated short-term
      intake. Part I-Calculation methods.
AB  - The calculation of the combined uncertainty of the international estimated short
      term intake (IESTI) of ethephon residues in apples is shown as an example. The
      ethephon residues in apples were reported by the Joint FAO (Food and Agriculture
      Organization of the United Nations)/WHO (World Health Organization) Meeting on
      Pesticide Residues (JMPR). The apple consumption data were taken from the IESTI
      (international short-term intake) calculation template used by the JMPR. The
      IESTI was calculated with the currently used method (case 2a) and a proposed one
      recommended by the EFSA (European Food Safety Authority)/RIVM (Dutch National
      Institute for Public Health) Scientific Workshop co-sponsored by FAO and WHO. In
      this example, the ratio of IESTIproposed/IESTIcurrent and their combined relative
      uncertainty are about 2.8, and 1.7, respectively. The larger IESTI and
      uncertainty obtained with the proposed equation are the consequence of
      calculation only with the large portion (LP) instead of its combination with unit
      mass, and the MRL instead of the highest residue (HR). The LP is the major
      contributor to the combined uncertainty. Both the calculated IESTI and its
      combined uncertainty depend on the actual food - pesticide residue combination,
      and should be calculated for each case.

PMID- 29584572
TI  - Foreword.

PMID- 29584573
TI  - Impact of a proposed revision of the IESTI equation on the acute risk assessment
      conducted when setting maximum residue levels (MRLs) in the European Union (EU):
      A case study.
AB  - Proposals to update the methodology for the international estimated short-term
      intake (IESTI) equations were made during an international workshop held in
      Geneva in 2015. Changes to several parameters of the current four IESTI equations
      (cases 1, 2a, 2b, and 3) were proposed. In this study, the overall impact of
      these proposed changes on estimates of short-term exposure was studied using the
      large portion data available in the European Food Safety Authority PRIMo model
      and the residue data submitted in the framework of the European Maximum Residue
      Levels (MRL) review under Article 12 of Regulation (EC) No 396/2005. Evaluation
      of consumer exposure using the current and proposed equations resulted in
      substantial differences in the exposure estimates; however, there were no
      significant changes regarding the number of accepted MRLs. For the different
      IESTI cases, the median ratio of the new versus the current equation is 1.1 for
      case 1, 1.4 for case 2a, 0.75 for case 2b, and 1 for case 3. The impact,
      expressed as a shift in the IESTI distribution profile, indicated that the 95th
      percentile IESTI shifted from 50% of the acute reference dose (ARfD) with the
      current equations to 65% of the ARfD with the proposed equations. This IESTI
      increase resulted in the loss of 1.2% of the MRLs (37 out of 3110) tested within
      this study. At the same time, the proposed equations would have allowed 0.4% of
      the MRLs (14 out of 3110) that were rejected with the current equations to be
      accepted. The commodity groups that were most impacted by these modifications are
      solanacea (e.g., potato, eggplant), lettuces, pulses (dry), leafy brassica (e.g.,
      kale, Chinese cabbage), and pome fruits. The active substances that were most
      affected were fluazifop-p-butyl, deltamethrin, and lambda-cyhalothrin.

PMID- 29584574
TI  - Effect of individual parameter changes on the outcome of the estimated short-term
      dietary exposure to pesticides.
AB  - In 2015 a scientific workshop was held in Geneva, where updating the
      International Estimate of Short-Term Intake (IESTI) equations was suggested. This
      paper studies the effects of the proposed changes in residue inputs, large
      portions, variability factors and unit weights on the overall short-term dietary
      exposure estimate. Depending on the IESTI case equation, a median increase in
      estimated overall exposure by a factor of 1.0-6.8 was observed when the current
      IESTI equations are replaced by the proposed IESTI equations. The highest
      increase in the estimated exposure arises from the replacement of the median
      residue (STMR) by the maximum residue limit (MRL) for bulked and blended
      commodities (case 3 equations). The change in large portion parameter does not
      have a significant impact on the estimated exposure. The use of large portions
      derived from the general population covering all age groups and bodyweights
      should be avoided when large portions are not expressed on an individual
      bodyweight basis. Replacement of the highest residue (HR) by the MRL and removal
      of the unit weight each increase the estimated exposure for small-, medium- and
      large-sized commodities (case 1, case 2a or case 2b equations). However, within
      the EU framework lowering of the variability factor from 7 or 5 to 3
      counterbalances the effect of changes in other parameters, resulting in an
      estimated overall exposure change for the EU situation of a factor of 0.87-1.7
      and 0.6-1.4 for IESTI case 2a and case 2b equations, respectively.

PMID- 29584575
TI  - Impact of proposed changes in IESTI equations for short-term dietary exposure to
      pesticides from Australian and Codex perspective.
AB  - In 2015 a scientific workshop was held in Geneva, where updating the four
      equations for estimating the short-term dietary exposure (International Estimated
      Short Term Intake, IESTI) to pesticides was suggested. The impact of these
      proposed changes on the exposure was studied by using residue data and large
      portion consumption data from Codex and Australia. For the Codex data, the
      exposure increased by a median factor of 2.5 per commodity when changing to the
      proposed IESTI equations. The increase in exposure was highest for bulked and
      blended food commodities (case 3 equations), followed by medium-sized food
      commodities (case 2a equations) and small- and large-sized food commodities (case
      1 and case 2b equations). For the Australian data, out of 184 maximum residue
      limit (MRL) large portion combinations showing acute exposures below the acute
      reference dose (ARfD) with the current IESTI equations, 23 exceeded the ARfD with
      the proposed IESTI equations (12%). The percentage exceeding the ARfD was higher
      for the Australian MRL large portion combinations (12% of 184) than for those of
      Codex (1.3% of 8,366). However, the percentage MRL loss in the Australian dataset
      may not be representative of all pesticide MRLs since it concerns six pesticides
      only, specifically selected to elucidate the potential effects of the use of the
      proposed IESTI equations. For the Codex data, the increase in exposure using the
      proposed equations resulted in a small increased loss of 2.6% of the 1,110 MRLs
      estimated by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR): 1.4% of the
      MRLs were already not acceptable with the current equations, 4.0% of the MRLs
      were not acceptable with the newly proposed equations. Our study revealed that
      case 3 commodities may be impacted more by the proposed changes than other
      commodities. This substantiates one of the conclusions of the Geneva workshop to
      gather information on bulking and blending practices in order to refine MRL
      setting and dietary risk assessment for case 3 commodities where possible.

PMID- 29584576
TI  - Improvements of Shooting Performance in Adolescent Air Rifle Athletes After a 6
      week Balance and Respiration Training Programs.
AB  - CONTEXT: Several factors, such as balance and respiration training programs, have
      been identified as contributing to the establishment of a shooting performance.
      However, little is known about the benefits of these programs on the shooting
      record, among adolescent air rifle athletes. OBJECTIVE: To determine whether
      there is a gain in the shooting record, among adolescent air rifle athletes,
      after participation in balance and respiration training programs. DESIGN: Case
      control study. SETTING: Shooting range. PARTICIPANTS: Twenty-one adolescent air
      rifle athletes were recruited from the local school community and assigned to an
      experimental (n=11; EG) or control (n=10; CG) group. INTERVENTION: The EG
      performed respiration and balance training for 30 min, three times a week for 6
      weeks, and the CG performed balance training only. MAIN OUTCOME MEASURES: Data
      were collected on the respiratory function, muscle activity, and shooting record,
      before and after the 6-week intervention. RESULTS: The forced vital capacity
      (FVC), forced expired volume in one second (FEV1), FEV1 as a percentage of FVC
      (FEV1/FVC), peak expiratory flow (PEF), and maximum voluntary ventilation (MVV)
      were significantly increased in the EG, and FEV1/FVC was significantly increased
      in the CG (p<0.05). The FVC and PEF, post-intervention, were significantly
      different between the groups (p<0.05). The activity of the right internal oblique
      (RTIO) and left internal oblique (LTIO) muscles of the FVC were significantly
      different in the EG (p<0.05). Within group changes in right external oblique
      (EO), RTIO, and LTIO of the MVV were significantly increased in the EG (p<0.05).
      The RTIO and LTIO activity improved more significantly in the EG than CG
      (p<0.05). There was no difference between the groups with respect to the shooting
      records. CONCLUSIONS: The experiment demonstrates that the balance and
      respiration training programs may help improve the respiratory function and
      muscle activity other than the shooting record.

PMID- 29584578
TI  - Longitudinal Associations of Metabolic Syndrome Severity Between Childhood and
      Young Adulthood: The Bogalusa Heart Study.
AB  - BACKGROUND: Childhood metabolic syndrome (MetS) is associated with insulin
      resistance and increased risk for later development of type 2 diabetes (T2DM) and
      cardiovascular disease (CVD). In using MetS severity z-scores, our objective was
      to assess longitudinal associations in MetS severity, fasting insulin levels as a
      sign of insulin resistance and risk for T2DM, and uric acid levels as a biomarker
      of oxidative stress leading to CVD. METHODS: We used linear regression to analyze
      longitudinal data from 285 white and black participants from the Bogalusa Heart
      Study evaluated at baseline at ages 5-19 and as young adults after a mean of 12.0
      years follow-up. We assessed correlations between childhood MetS severity and
      young-adult MetS severity, fasting insulin, and uric acid levels, both overall
      and by sex- and racial subgroups. RESULTS: Overall, childhood MetS z-scores were
      positively associated with young-adult MetS z-scores (r = 0.52), insulin (r =
      0.34), and uric acid (r = 0.28) (all P < 0.001). These associations were
      consistent across all sex- and racial subgroups, except for young adult uric acid
      in white males in which childhood MetS-z was not associated (r = 0.15, P =
      0.243). There was a strong cross-sectional association of young-adult MetS z
      scores with insulin (r = 0.70) and uric acid (r = 0.57) (both P < 0.001), which
      was consistent for all sex- and racial subgroups. CONCLUSIONS: These positive
      longitudinal correlations between childhood MetS z-scores and markers of later
      insulin resistance and oxidative stress suggest long-term durability of risk for
      CVD and T2DM. This suggests potential for MetS severity to serve as an indicator
      to monitor for future risk of T2DM and CVD.

PMID- 29584579
TI  - Prevalence of Pyrazinamide Resistance in Khyber Pakhtunkhwa, Pakistan.
AB  - AIMS: Pyrazinamide (PZA) is an important component of first-line tuberculosis
      (TB) treatment because of its distinctive capability to kill subpopulations of
      persister Mycobacterium tuberculosis (MTB). The significance of PZA can be
      understood by its inclusion in the most recent World Health Organization
      recommended multidrug-resistant (MDR) TB regimen. Very little information is
      available about the prevalence of PZA-resistant TB from geographically distinct
      regions of high burden countries, including Khyber Pakhtunkhwa (KPK), Pakistan,
      because drug susceptibility testing (DST) of PZA is not regularly performed due
      to the complexity. In this study, we aimed to find the prevalence of PZA
      resistance in geographically distinct, Pashtun-dominant KPK Province of Pakistan
      and its correlation with other first- and second-line drug resistance. MATERIALS
      AND METHODS: In this study, DST of PZA was performed through an automated BACTEC
      MGIT 960 system (BD Diagnostic Systems). The resistant samples were further
      subjected to DST of isoniazid (INH), rifampicin (RIF), ethambutol (EMB),
      streptomycin (SM), moxicillin (MOX), amikacin (AMK), ofloxacin (OFX), kanamycin
      (KM), and capreomycin (CAP). RESULTS: Out of 1,075 MTB-positive isolates, 83
      (7.7%) were found to be resistant to PZA. Among the PZA-resistant isolates, 76
      (90-91.6%) and 67 (80-80.7%) were found to be resistant to INH and RIF,
      respectively, whereas 63 (76%) were resistant to both first-line drugs, INH and
      RIF (MDR-TB). The resistance level of EMB, OFX, and SM was also significantly
      high in PZA resistance, 35 (42%), 40 (48%), and 41 (49-50%) respectively.
      CONCLUSION: PZA resistance is significantly associated with other first- and
      second-line drug resistance. A significant number of PZA-resistant isolates are
      MDR cases. Therefore, DST of PZA should regularly be performed along with other
      drugs for better management of treatment of MDR and extensively drug resistant
      (XDR), to avoid side effects in patients.

PMID- 29584577
TI  - How Should Biobanks Prioritize and Diversify Biosample Collections? A 40-Year
      Scientific Publication Trend Analysis by the Type of Biosample.
AB  - Biobanks are infrastructures for large-scale biology innovation. Governance of
      biobanks can be usefully informed by studies of publication trends, for example,
      on the types of biosamples employed in scientific publications. We examined
      trends in each of the serum, plasma, peripheral blood mononuclear cell (PBMC),
      buffy coat, tissue, and gut microbiome biosample-related scientific publications
      over the past 40 years, using data between 1977 and 2016 from the Scopus
      database. We found that the number of tissue-related publications was the highest
      in each year of our analysis than other biosamples, but was generally less than
      the sum of serum- and plasma-related publications. Importantly, the microbiome
      publications increased greatly starting in the 2010s, and currently overtook the
      number of publications on PBMC and buffy coat. Among serum-, plasma-, and tissue
      related publications, the number of protein- and RNA-related publications was
      generally higher than cell-free DNA-, DNA-, and metabolite-related publications
      for the past 40 years. Mass spectrometry- and next-generation sequencing-related
      publications have increased dramatically since the 2000s and 2010s, respectively.
      Microbiome- and metabolite-related biosamples can help diversify future biosample
      collections, while tissue collections appear to maintain their importance in
      scientific publications. We also report here our observations on the countries
      that use biosample research (e.g., China, United Kingdom, United States, and
      others). These publication trends by the type of biosamples illuminate roadmaps
      by which biobanks might establish and diversify their biosample collections in
      the future. In addition, we note that biobanks need to secure biosamples
      appropriate for integrated analysis of multi-omics research data.

PMID- 29584580
TI  - Differences in Timed Up and Go Subtasks Between Older People With Mild Cognitive
      Impairment and Mild Alzheimer's Disease.
AB  - This study compared performances of timed up and go test subtasks between 40
      older people with preserved cognition, 40 with mild cognitive impairment, and 38
      with mild Alzheimer's disease. The assessment consisted of anamneses and timed up
      and go test subtasks (sit-to-stand, walking forward, turn, walking back, and turn
      to-sit). Data were captured by Qualisys Track Manager software and processed by
      Visual3D software. The MATLAB program was applied to detect and analyze timed up
      and go test subtasks. All subtasks differentiated people with Alzheimer's disease
      and preserved cognition, except the sit-to-stand subtask, which did not
      distinguish any group. The walking forward subtask differed older people with
      preserved cognition from mild cognitive impairment, specifically on minimum peak
      of knee, average value of knee, and hip (pitch axis) during stance phase. The
      walking back, turn, and turn-to-sit subtasks distinguished subjects with
      Alzheimer's disease from mild cognitive impairment. The separated analysis of
      transition and walking subtasks is important in identifying mobility patterns
      among cognitive profiles.

PMID- 29584581
TI  - Steps to Misdiagnosis: Dissecting an Emergency Visit.
AB  - Despite the common sense that we learn from our mistakes, an error is an
      unwelcome event when we deal with patients. Diagnostic error is common, costly,
      and the leading cause of malpractice litigation. Yet, errors occur occasionally
      in a lifetime of practice, and the consequences of these faults are significant
      for patients and physicians. If someone would have told me that I would miss a
      brain tumor in my first years of practice, in a patient presenting to my care
      with several cranial nerve signs, I would not have believed it. Here is how it
      happened.

PMID- 29584582
TI  - Building Global Genomics Initiatives and Enabling Data Sharing: Insights from
      Multiple Case Studies.
AB  - This genomics global governance research study presents the dynamics and the
      evolving nature of salient challenges that global genomics initiatives encounter
      in designing new models for data management, exchange, and collaboration across
      disciplines, sectors, and countries. Using a multiple case study approach, we
      assessed and compared organizational responses across diverse genomics
      initiatives. The richness of a comparative qualitative analysis clearly shows the
      complexity addressed by genomics initiatives and, importantly, expands current
      studies by moving beyond an open versus property regime dichotomy. Although we
      identify some common themes, fundamental differences emerge in the way genomics
      initiatives set goals, manage heterogeneity, define resources, devise governance,
      and enable data sharing. Such differences demonstrate the ongoing processes of
      adapting governance structures, management processes, and organizational design
      solutions that are implemented in response to different social, technical, and
      policy environments. We find that genomics initiatives largely benefit from and
      are shaped by the engagement with large communities of scientists to rethink and
      design shared rules and guidelines for data exchange and use. Our study provides
      direct guidance to future global genomics initiatives, but it also offers a
      benchmark for research in the omics field broadly, both in terms of design and
      methodological approaches to understand the emerging forms of scientific
      governance and innovation ecosystems.

PMID- 29584583
TI  - Involvement of the SnRK1 subunit KIN10 in sucrose-induced hypocotyl elongation.
AB  - A mechanism participating in energy sensing and signalling in plants involves the
      regulation of sucrose non-fermenting1 (Snf1)-related protein kinase 1 (SnRK1)
      activity in response to sugar availability. SnRK1 is thought to regulate the
      activity of both metabolic enzymes and transcription factors in response to
      changes in energy availability, with trehalose-6-phospate functioning as a
      signalling sugar that suppresses SnRK1 activity under sugar-replete conditions.
      Sucrose supplementation increases the elongation of hypocotyls of developing
      Arabidopsis seedlings, and this response to sucrose involves both the SnRK1
      subunit KIN10 and also TREHALOSE-6-PHOSPHATE SYNTHASE1 (TPS1). Here, we measured
      sucrose-induced hypocotyl elongation in two insertional mutants of KIN10 (akin10
      and akin10-2). Under short photoperiods, sucrose supplementation caused great
      proportional hypocotyl elongation in these KIN10 mutants compared with the wild
      type, and these mutants had shorter hypocotyls than the wild type in the absence
      of sucrose supplementation. One interpretation is that SnRK1 activity might
      suppress hypocotyl elongation in the presence of sucrose, because KIN10
      overexpression inhibits sucrose-induced hypocotyl elongation and akin10 mutants
      enhance sucrose-induced hypocotyl elongation.

PMID- 29584584
TI  - Adsorption behaviours and mechanisms of heavy metal ions' impact on municipal
      waste composts with different degree of maturity.
AB  - Composting may change the adsorption characteristics and mechanisms of organic
      materials due to their differences in organic chemical functional groups and
      surface structures. The adsorption properties of heavy metals onto the municipal
      solid waste compost (MSW-C) and its secondary fermentation form (MSW-SC) were
      comparatively investigated in single, binary and multiple solutions by batch
      experiments. In the single-metal system, the maximum adsorption capacities of Cu,
      Zn, Cd and Ni onto MSW-SC were 29.2, 26.3, 38.1 and 22.0 mg g-1, respectively,
      and showed higher than that of MSW-C. The adsorption fitted best with the pseudo
      second-order kinetics and Langmuir isotherms. The competitive adsorption results
      indicated that the composts exhibited good selectivity in the adsorption of Cu
      over Cd, Zn and Ni; thus, for the quaternary-metal systems, the adsorption
      sequence was Cu > Zn > Cd > Ni. Humic acid content, cation exchange capacity and
      surface area were increased following the secondary composting. FTIR analysis
      indicated amine and aromatic compounds were main binding sites accounting for
      metal sorption. SEM-EDX analysis suggested that the MSW-SC had rough surfaces and
      stronger adsorption capacity. Decreasing percentage of exchangeable metals was
      found in the metal-loaded MSW-SC based on a speciation analysis. This study
      highlights the interactive impacts of different metals during adsorption by
      compost with different maturity, the secondary composting process was a
      multifunctional improvement of sorption characteristics and MSW-SC was developed
      to be a highly efficient biosorbent.

PMID- 29584585
TI  - Journey of siRNA: Clinical Developments and Targeted Delivery.
AB  - Since the evolutionary discovery of RNA interference and its utilization for gene
      knockdown in mammalian cell, a remarkable progress has been achieved in small
      interfering RNA (siRNA) therapeutics. siRNA is a promising tool, utilized as
      therapeutic agent against various diseases. Despite its significant potential
      benefits, safe, efficient, and target oriented delivery of siRNA is one of the
      major challenges in siRNA therapeutics. This review covers major achievements in
      clinical trials and targeted delivery of siRNAs using various targeting ligand
      receptor pair. Local and systemically administered siRNA drug candidates at
      various phases in clinical trials are described in this review. This review also
      provides a deep insight in development of targeted delivery of siRNA. Various
      targeting ligand-siRNA pair with complexation and conjugation approaches are
      discussed in this review. This will help to achieve further optimization and
      development in targeted delivery of siRNAs to achieve higher gene silencing
      efficiency with lowest siRNA dose availability.

PMID- 29584586
TI  - Characterization of ash melting behaviour at high temperatures under conditions
      simulating combustible solid waste gasification.
AB  - To achieve high-temperature gasification-melting of combustible solid waste, ash
      melting behaviour under conditions simulating high-temperature gasification were
      studied. Raw ash (RA) and gasified ash (GA) were prepared respectively by waste
      ashing and fluidized bed gasification. Results of microstructure and composition
      of the two-ash indicated that GA showed a more porous structure and higher
      content of alkali and alkali earth metals among metallic elements. Higher
      temperature promoted GA melting and could reach a complete flowing state at about
      1250 degrees C. The order of melting rate of GA under different atmospheres was
      reducing condition > inert condition > oxidizing condition, which might be
      related to different existing forms of iron during melting and different flux
      content with atmosphere. Compared to RA, GA showed lower melting activity at the
      same condition due to the existence of an unconverted carbon and hollow
      structure. The melting temperature for sufficient melting and separation of GA
      should be at least 1250 degrees C in this work.

PMID- 29584587
TI  - Behavioral Effects of Focal Irradiation in a Juvenile Murine Model.
AB  - Chemotherapy has been successfully used to reduce radiation dose and volume for
      most pediatric patients. However, because of the failure of chemotherapeutic
      agents to cross the blood-brain barrier and the lack of response of some brain
      tumors to these agents, radiation therapy is still used to treat many childhood
      cancers with CNS involvement. In this study, we investigated the radiation
      effects on cognition and dendritic structure in the hippocampus in juvenile male
      mice. Twenty-one-day-old male C57BL/6 mice were irradiated using the small animal
      radiation research platform (SARRP). Animals were exposed to either a 10 Gy
      single dose or 10 Gy * 2 fractionated doses of X-ray cranial radiation. Five
      weeks after irradiation, animals were tested for hippocampus-dependent cognitive
      performance in the Morris water maze. Significant impairment in spatial memory
      retention was observed in the probe trial after the first day of hidden-platform
      training (first probe trial) in animals that received either 10 Gy single-dose or
      10 Gy * 2 fractionated doses. However, by day 5, mice that received a 10 Gy
      single dose showed spatial memory retention in the probe trials, whereas mice
      that received the 20 Gy fractionated doses remained impaired. During Y-maze
      testing, animals exposed to radiation were impaired; the irradiated mice were not
      able to distinguish among the three Y-maze arms and spent approximately the same
      amount of time in all three arms during the retention trial. Radiation
      significantly compromised the dendritic architecture and reduced spine density
      throughout the hippocampal trisynaptic network.

PMID- 29584589
TI  - Molecular Characterization and Phylogenetic Analysis of Anaplasma spp. and
      Ehrlichia spp. Isolated from Various Ticks in Southeastern and Northwestern
      Regions of Iran.
AB  - INTRODUCTION: Anaplasma/Ehrlichia species are tick-transmitted pathogens that
      cause infections in humans and numerous domestic and wild animal species. There
      is no information available on the molecular characteristics and phylogenetic
      position of Anaplasma/Ehrlichia spp. isolated from tick species from different
      geographic locations in Iran. The aim of this study was to determine the
      prevalence, molecular characteristics, and phylogenetic relationship of both
      Anaplasma spp. and Ehrlichia spp. in tick species isolated from different
      domestic animals from two different geographical locations of Iran. METHODS: A
      total of 930 ticks were collected from 93 cattle, 250 sheep, and 587 goats
      inhabiting the study areas. The collected ticks were then investigated for the
      presence of Anaplasma/Ehrlichia spp. using nested PCR based on the 16S rRNA gene,
      followed by sequencing. Sequence analysis was done based on the data published in
      the GenBank on Anaplasma/Ehrlichia spp. isolates using bioinformatic tools such
      as the standard nucleotide BLAST. RESULTS: Genome of Anaplasma or Ehrlichia spp.
      was detected in 14 ticks collected in Heris, including 5 Dermacentor marginatus,
      1 Haemaphysalis erinacei, 3 Hyalomma anatolicum, and 4 Rhipicephalus sanguineus,
      also in 29 ticks collected in Chabahar, including 14 R. sanguineus, 8 D.
      marginatus, 3 Hyalomma Anatolicum, and 4 Hyalomma dromedarii. Partial analysis of
      the 16S rRNA gene sequence of positive samples collected from goats and sheep
      showed that they were infected with Anaplasma/Ehrlichia spp. that were 94-98%
      identical to ovine Anaplasma and 91-96% identical to Neoehrlichia and Ehrlichia
      spp. CONCLUSION: The various ticks identified in this study suggest the possible
      emergence of tick-borne diseases in animals and humans in these regions. R.
      sanguineus and D. marginatus seem to be predominant vectors responsible for
      anaplasmosis in these regions. Partial sequence analysis of the 16S rRNA gene
      showed that A. ovis is genetically polymorphic in these regions. Furthermore, an
      association between the genetic heterogeneity of this microorganism and the
      geographical regions of Anaplasma strains was found. This study also showed that
      those ticks that were collected from the same geographical origin were infected
      with closely related strains of Anaplasma.

PMID- 29584588
TI  - Amelioration of Head and Neck Radiation-Induced Mucositis and Distant Marrow
      Suppression in Fanca-/- and Fancg-/- Mice by Intraoral Administration of GS
      Nitroxide (JP4-039).
AB  - Squamous cell carcinomas of the head and neck are appearing with increased
      frequency in both marrow transplanted and non-transplanted Fanconi anemia (FA)
      patients. FA patients commonly display radiosensitivity of epithelial tissues,
      complicating effective radiotherapy. Fancd2-/- mice (C57BL/6J and 129/Sv
      background) demonstrate epithelial tissue sensitivity to single-fraction or
      fractionated irradiation to the head and neck and distant marrow suppression
      (abscopal effect), both ameliorated by intraoral administration of the
      mitochondrial-targeted antioxidant, GS-nitroxide, JP4-039. We now report that
      mice of two other FA genotypes, Fancg-/- (B6) and the most prevalent human
      genotype Fanca-/- (129/Sv), also demonstrate: 1. reduced longevity of
      hematopoiesis in long-term bone marrow cultures; 2. radiosensitivity of bone
      marrow stromal cell lines; and 3. head and neck radiation-induced severe
      mucositis and abscopal suppression of distant marrow hematopoiesis. Intraoral
      administration of JP4-039/F15, but not non-mitochondrial-targeted 4-amino
      Tempo/F15 or F15 alone, prior to each radiation treatment ameliorated both local
      and abscopal radiation effects. Head and neck irradiated TGF-beta-resistant SMAD3
      /- (129/Sv) mice and double-knockout SMAD3-/- Fancd2-/- (129/Sv) mice treated
      daily with TGF-beta receptor antagonist, LY364947, still displayed abscopal bone
      marrow suppression, implicating a non-TGF-beta mechanism. Thus, amelioration of
      both local normal tissue radiosensitivity and distant marrow suppression by
      intraoral administration of JP4-039 in Fancg-/- and Fanca-/- mice supports a
      clinical trial of this locally administered normal tissue radioprotector and
      mitigator during head and neck irradiation in FA patients.

PMID- 29584590
TI  - Maternal Thyroid Function in Early Pregnancy and Child Neurodevelopmental
      Disorders: A Danish Nationwide Case-Cohort Study.
AB  - BACKGROUND: Maternal thyroid dysfunction may adversely affect fetal brain
      development, but more evidence is needed to refine this hypothesis. The aim of
      this study was to evaluate potential fetal programming by abnormal maternal
      thyroid function on child neurodevelopmental disorders. METHODS: The design was a
      case-cohort study within the Danish National Birth Cohort (1997-2003). From the
      eligible cohort of 71,706 women, a random 12% sub-cohort (n = 7624) was selected,
      and all women (n = 2276) whose child was diagnosed with seizures, specific
      developmental disorder (SDD), autism spectrum disorder (ASD), and/or attention
      deficit/hyperactivity disorder (ADHD) up to December 31, 2010, were identified.
      All women had a blood sample drawn in early pregnancy (median week 9), and the
      stored sample was used for measurement of free thyroxine and thyrotropin. Method-
      and week-specific reference ranges were used for classification of maternal
      thyroid function. A weighted Cox proportional hazards model was used to estimate
      adjusted hazard ratio (aHR) with 95% confidence intervals (CI) for
      neurodevelopmental disorders in children exposed to maternal thyroid dysfunction.
      RESULTS: The overall frequency of abnormal maternal thyroid function was 12.5% in
      the sub-cohort and significantly higher among cases of ASD (17.9%; aHR = 1.5 [CI
      1.1-2.1]), but not among other types of neurodevelopmental disorders (febrile
      seizures: 12.7%; epilepsy: 13.1%; SDD: 12.6%; and ADHD: 14.0%). However,
      evaluation of subtypes of maternal thyroid dysfunction showed that maternal overt
      hypothyroidism (thyrotropin >10 mIU/L) was a risk factor for epilepsy in the
      child (aHR = 3.5 [CI 1.2-10]), as was overt hyperthyroidism for cases diagnosed
      within the first year of life (aHR = 3.0 [CI 1.03-8.4]). Furthermore, both
      maternal hypothyroidism (aHR = 1.8 [CI 1.1-2.7]) and overt hyperthyroidism (aHR =
      2.2 [CI 1.1-4.4]) were risk factors for ASD in the child, and isolated low free
      thyroxine was associated with ASD (aHR = 4.9 [CI 2.03-11.9]) and ADHD (aHR = 2.3
      [CI 1.2-4.3]) in girls but not in boys. CONCLUSIONS: Abnormal maternal thyroid
      function in early pregnancy was associated with epilepsy, ASD, and ADHD in the
      child, but associations differed by subtypes of exposure and by child age and
      sex. More evidence on subtypes and severity of maternal thyroid function is
      needed, and alternative outcomes of child neurodevelopment may be warranted.

PMID- 29584591
TI  - Genetic variants of vascular endothelial growth factor predict risk and survival
      of gliomas.
AB  - The vascular endothelial growth factor regulates angiogenesis that is increased
      in glioma. VEGF polymorphisms are thought to modulate vascular endothelial growth
      factor plasma levels and therefore may be implicated in glioma risk. We aimed to
      clarify the role of VEGF and von Willebrand factor polymorphisms in glioma
      susceptibility and prognosis. A case-control study of 126 glioma patients and 180
      cancer-free controls was performed. Using Sequenom MassARRAY platform, 11 VEGF
      and 1 VWF polymorphisms were genotyped. Unconditional multivariate logistic
      regression models were used to calculate odds ratios and 95% confidence
      intervals. The associations between polymorphisms and survival were evaluated
      using a Cox regression model. Bonferroni's adjustment was used to correct for
      multiple testing. The VEGF polymorphism rs833061 was strongly associated with
      increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio =
      155.66), confirmed after Bonferroni correction. Also, the VEGF polymorphisms
      rs3024994, rs2010963, and particularly the homozygous carriers of rs1005230 were
      associated with a worse prognosis for glioma and glioblastoma. Our data support a
      role of VEGF and VWF polymorphisms as glioma biomarkers, with additional
      potential relevance for molecular stratification of patients for anti-angiogenic
      therapies.

PMID- 29584592
TI  - Corrigendum.
AB  - Vila PM, Zenga J, Fowler S, Jackson RS. Antibiotic prophylaxis in clean
      contaminated head and neck surgery: a systematic review and meta-analysis.
      Otolaryngol Head Neck Surg. 2017;157:580-588. (Original DOI:
      10.1177/0194599817712215) This article was printed in the October 2017 issue with
      the third author, Susan Fowler, omitted. The online version of this article has
      been corrected to accurately reflect Susan Fowler's authorship: Susan Fowler's
      name was added as the third author in the byline and her affiliation was added to
      the footnotes (Washington University in St Louis, St Louis, Missouri, USA). Her
      contributions have also been added to the Author Contributions section.

PMID- 29584593
TI  - Outcome of Architectural Distortion Detected Only at Breast Tomosynthesis versus
      2D Mammography.
AB  - Purpose To compare the outcome of architectural distortion (AD) without
      associated mass only on digital breast tomosynthesis (DBT) with AD seen at two
      dimensional (2D) mammography and to evaluate if the incidence of malignancy is
      influenced by the presence of a correlate at ultrasonography (US). Materials and
      Methods This retrospective study had institutional review board approval and was
      HIPAA compliant. All consecutive cases in which patients with AD were ultimately
      assigned Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 categories
      from 2009 to 2016 were reviewed by three readers for visibility (2D vs DBT). The
      level of suspicion was assigned using a Likert scale. Pathologic results were
      compared between 2D-detected and DBT-detected AD. Frequencies were compared by
      using the McNemar and Pearson chi2 exact tests. Results One hundred eighty-one AD
      lesions were included; 122 (67.4%) were 2D visible while 59 (32.6%) were DBT
      detected. Forty-two women (with 43 lesions) underwent 2D mammography prior to
      initiation of DBT. In 117 women with 121 AD lesions who underwent 2D mammography
      plus DBT, 59 lesions (48.8%) were detected only with DBT. The malignancy rate
      based on final pathology was significantly higher for 2D-detected AD (53 [43.4%]
      of 122) compared with DBT (six [10.2%] of 59) (P < .001). A US correlate was more
      frequent with 2D-detected AD (103 [84.4%] of 122) than DBT (33 [55.9%] of 59) (P
      < .001). Malignancy rate was not different for DBT-detected AD with (four [12.1%]
      of 33; 95% confidence interval [CI]: 3.4%, 28.2%]) or without (two [7.7%] of 26;
      95% CI: 0.9%, 25.1%]) a US correlate. NPV based on radiologists' level of
      suspicion was high (91.8%-98.0%) but not sufficient enough to forgo biopsy.
      Conclusion DBT-detected suspicious AD has a lower malignancy outcome compared
      with 2D mammography-detected suspicious AD, although still high enough to warrant
      biopsy. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 29584595
TI  - Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to
      Predict Patient Survival.
AB  - Purpose To determine the performance of magnetic resonance (MR) imaging-based
      tumor metrics for evaluation of response to transarterial chemoembolization
      (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA).
      Materials and Methods Ninety-four patients with unresectable ICCA underwent
      baseline and follow-up MR imaging after TACE and were followed up until death or
      end of study duration. Lesions were analyzed for anatomic (Response Evaluation
      Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor
      volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric
      MR parameters by using semiautomatic software. Response was assessed by using
      changes in viable tumor volume by using modified RECIST (mRECIST)-derived
      thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall
      survival was the primary endpoint. Cox-regression and Kaplan-Meier survival
      analysis were used. Results Tumor volume did not change after TACE (P = .07)
      whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an
      increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable
      tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among
      responders by using thresholds of 25% increase in ADC, 66% decrease in viable
      tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05).
      Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and
      viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009),
      and 4.0 (P = .002), respectively. Survival differences were noted for patients
      who showed response by using all three parameters (ADC, three-dimensional
      mRECIST, and viable tumor burden) versus those who showed response by using
      either one or two of these parameters versus those who showed no response (P <
      .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable
      tumor burden at MR imaging provide prognostic information among patients with
      unresectable ICCA who undergo TACE. (c) RSNA, 2018 Online supplemental material
      is available for this article.

PMID- 29584594
TI  - Acoustic Radiation Force Impulse US Imaging: Liver Stiffness in Patients with
      Chronic Hepatitis B with and without Antiviral Therapy.
AB  - Purpose To investigate the clinical utility and longitudinal change of acoustic
      radiation force impulse (ARFI) ultrasonographic (US) imaging in patients with
      chronic hepatitis B. Materials and Methods A retrospective cohort study of
      patients with chronic hepatitis B who underwent serial ARFI examinations in a
      tertiary referral center in Taiwan between 2012 and 2016 was conducted. The
      clinical information and noninvasive liver stiffness measurement tests (ARFI,
      Fibrosis-4 index [FIB-4], and FibroScan) were collected. Serial ARFI measurements
      were compared in patients without antiviral therapy (nontreatment group) and
      during antiviral therapy (treatment group). The linear mixed-effects model with
      random coefficients was used to compare longitudinal repeated measurements.
      Results A total of 559 patients undergoing serial ARFI examinations were
      included. The ARFI value correlated with FIB-4 (correlation coefficient = 0.55, P
      < .001) and FibroScan (correlation coefficient = 0.69, P < .001) results. There
      were 314 patients with five or more ARFI measurements in more than 3 years of
      follow-up. The ARFI value remained unchanged in the nontreatment group (n = 189,
      from 1.11 to 1.11 m/sec, time trend P = .911). However, the ARFI value declined
      significantly in the treatment group (n = 125, from 1.63 to 1.37 m/sec, time
      trend P < .001), both in patients with cirrhosis (n = 51, from 2.15 to 1.75
      m/sec, time trend P < .001) and in those without (n = 74, from 1.27 to 1.11
      m/sec, time trend P < .001). Conclusion ARFI US imaging is an important clinical
      noninvasive test for liver stiffness measurement and can be used for serial
      measurements in the management of chronic hepatitis B. Antiviral therapy
      significantly reduces liver stiffness during longitudinal follow-up.

PMID- 29584596
TI  - Estimating the Patient-specific Dose to the Thyroid and Breasts and Overall Risk
      in Chest CT When Using Organ-based Tube Current Modulation.
AB  - Purpose To assess the potential dose reduction to the thyroid and breasts in
      chest computed tomography (CT) with organ-based tube current modulation (OBTCM).
      Materials and Methods In this retrospective study (from January 2015 to December
      2016), the location of the breasts with respect to the reduced tube current zone
      was determined. With Monte Carlo simulations, patient-specific dose distributions
      of chest CT scans were calculated for 50 female patients (mean age, 53.7 years +/
      17.5; range, 20-80 years). The potential dose reduction with OBTCM was assessed.
      In addition, simulations of clinical OBTCM scans were made for 17 of the 50
      female patients (mean age, 43.8 years +/- 17.1; range, 20-69 years). Posterior
      organs in the field of view were analyzed and lifetime attributable risk (LAR) of
      cancer incidence and mortality was estimated. Image quality between standard CT
      and OBTCM scans was compared. Results No women had all breast tissue within the
      reduced tube current zone. Dose reductions of 18% in the thyroid and 9% in the
      breasts were observed, whereas the doses in lung, liver, and kidney were 17%,
      11%, and 26% higher. Overall, the LAR for cancer incidence was not significantly
      different between conventional and OBTCM scanning (P = .06). Image quality
      improved with OBTCM (P < .002). Conclusion The potential benefit of OBTCM to the
      female breast in chest CT is overestimated because of a limited reduced tube
      current zone; despite a 9% dose reduction to the female breast, posterior organs
      will absorb up to 26% more radiation, resulting in no reduction in radiation
      induced malignancies. (c) RSNA, 2018.

PMID- 29584597
TI  - Advanced Hepatocellular Carcinoma: Pretreatment Contrast-enhanced CT Texture
      Parameters as Predictive Biomarkers of Survival in Patients Treated with
      Sorafenib.
AB  - Purpose To determine whether texture features on pretreatment contrast material
      enhanced computed tomographic (CT) images can help predict overall survival (OS)
      and time to progression (TTP) in patients with advanced hepatocellular carcinoma
      (HCC) treated with sorafenib. Materials and Methods This retrospective study
      included 92 patients with advanced HCC treated with sorafenib between January
      2009 and April 2015 at two independent university hospitals. Sixty-four of the 92
      patients (70%) (six women, 58 men; median age, 66 years) were included from
      institution 1 and constituted a training cohort; 28 patients (30%) (five women,
      23 men; median age, 64 years) were included from institution 2 and constituted a
      validation cohort. Pretreatment CT texture analysis was performed on late
      arterial and portal venous phase HCC images. Mean gray-level intensity, entropy,
      kurtosis, skewness, and standard deviation values were derived from the pixel
      distribution histogram before and after spatial filtration at different anatomic
      scales ranging from fine to coarse texture. Lesion heterogeneity was also
      visually graded on a 4-point scale. Correlations between visual analysis and
      texture parameters were assessed with the Spearman rank correlation. Univariate
      Kaplan-Meier and multivariate Cox proportional hazards regression analyses were
      performed in the training cohort to identify independent predictors of OS and
      TTP. Their predictive capacity was tested on the validation cohort by using
      Kaplan-Meier analysis. Results Visual analysis of tumor heterogeneity correlated
      with entropy at both arterial (P = .012) and portal venous (P = .038) phases.
      Portal phase-derived entropy at fine (hazard ratio [HR], 5.08; P = .0033), medium
      (HR, 2.23; P = .019), and coarse (HR, 2.26; P = .0032) texture scales was
      identified as an independent predictor of OS and confirmed in the validation
      cohort (P < .05). The difference in median survival between patients in the
      validation cohort with entropy values below and above the identified threshold
      was 272 days (with fine texture) and 741 days (with medium and coarse textures).
      Arterial phase-derived texture parameters (P > .085) and visual analysis (P >
      .11) were not associated with changes in survival. Conclusion Pretreatment portal
      venous phase-derived tumor entropy may be a predictor of survival in patients
      with advanced HCC treated with sorafenib.

PMID- 29584598
TI  - Use of 2D U-Net Convolutional Neural Networks for Automated Cartilage and
      Meniscus Segmentation of Knee MR Imaging Data to Determine Relaxometry and
      Morphometry.
AB  - Purpose To analyze how automatic segmentation translates in accuracy and
      precision to morphology and relaxometry compared with manual segmentation and
      increases the speed and accuracy of the work flow that uses quantitative magnetic
      resonance (MR) imaging to study knee degenerative diseases such as osteoarthritis
      (OA). Materials and Methods This retrospective study involved the analysis of 638
      MR imaging volumes from two data cohorts acquired at 3.0 T: (a) spoiled gradient
      recalled acquisition in the steady state T1rho-weighted images and (b) three
      dimensional (3D) double-echo steady-state (DESS) images. A deep learning model
      based on the U-Net convolutional network architecture was developed to perform
      automatic segmentation. Cartilage and meniscus compartments were manually
      segmented by skilled technicians and radiologists for comparison. Performance of
      the automatic segmentation was evaluated on Dice coefficient overlap with the
      manual segmentation, as well as by the automatic segmentations' ability to
      quantify, in a longitudinally repeatable way, relaxometry and morphology. Results
      The models produced strong Dice coefficients, particularly for 3D-DESS images,
      ranging between 0.770 and 0.878 in the cartilage compartments to 0.809 and 0.753
      for the lateral meniscus and medial meniscus, respectively. The models averaged 5
      seconds to generate the automatic segmentations. Average correlations between
      manual and automatic quantification of T1rho and T2 values were 0.8233 and
      0.8603, respectively, and 0.9349 and 0.9384 for volume and thickness,
      respectively. Longitudinal precision of the automatic method was comparable with
      that of the manual one. Conclusion U-Net demonstrates efficacy and precision in
      quickly generating accurate segmentations that can be used to extract relaxation
      times and morphologic characterization and values that can be used in the
      monitoring and diagnosis of OA. (c) RSNA, 2018 Online supplemental material is
      available for this article.

PMID- 29584599
TI  - Alterations of White Matter Connectivity in Preschool Children with Autism
      Spectrum Disorder.
AB  - Purpose To investigate the topologic architecture of white matter connectivity
      networks in preschool-aged children with a diagnosis of autism spectrum disorder
      (ASD) versus typical development (TD). Materials and Methods Forty-two
      participants were enrolled, including 21 preschool children with ASD (14 male
      children and seven female children; mean age, 4.56 years +/- 0.97 [standard
      deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13
      years +/- 0.82). The diagnosis of ASD was determined according to the Diagnostic
      and Statistical Manual of Mental Disorders Global Assessment of Functioning
      scores (mean score, 8.00 +/- 0.50). All participants underwent diffusion-tensor
      imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph
      theoretical analysis was applied to investigate the topologic organization of the
      brain network including global and local topologic parameters. Statistical
      analysis was then performed for the comparison between the groups. Results
      Compared with the TD group, children with ASD demonstrated shortened
      characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and
      t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3
      = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 =
      0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant
      increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032,
      respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P
      < .01) of the basal ganglia network. Conclusion Significantly altered patterns of
      global and local brain network topography may underlie the abnormal brain
      development in preschool children with ASD compared with those who have TD. The
      identification of altered structural connectivity in basal ganglia and paralimbic
      limbic networks may point toward potential imaging biomarkers for preschool-age
      patients with ASD. (c) RSNA, 2018.

PMID- 29584601
TI  - Application of Viable Cryopreserved Human Placental Membrane Grafts in the
      Treatment of Wounds of Diverse Etiologies: A Case Series.
AB  - : There is evidence in the literature that viable cryopreserved human placental
      membrane (vCHPM) grafts are effective in treating diabetic foot ulcers and venous
      leg ulcers. OBJECTIVE: This case series presents 3 cases of chronic ulcerations -
      1 arterial ulcer (AU), 1 pressure ulcer (PU), and 1 recurrence of a pyoderma
      gangrenosum ulcer (PGU) - that had failed previous courses of standard wound care
      and were subsequently treated with vCHPM to determine if the treatment is an
      effective modality for treating wounds of these etiologies. MATERIALS AND
      METHODS: This retrospective review describes 3 cases in which patients with
      chronic wounds that had failed standard of care treatments for more than 4 weeks
      were subsequently treated with weekly applications of vCHPM. Each wound area was
      recorded and photographed on a weekly basis and wound area reduction also was
      charted weekly. RESULTS: The PU and AU both reached full closure in 4 and 5
      weeks, respectively, without complication. The patient with the PGU achieved 64%
      closure after 9 applications of vCHPM. CONCLUSIONS: Viable CHPM is an effective
      treatment modality for wounds of diverse etiologies and shows better results than
      have been previously published with standard of care. In patients with PGUs,
      medical optimization and close management of comorbidities is essential in
      achieving optimal results.

PMID- 29584602
TI  - Effect of a New Purified Collagen Matrix With Polyhexamethylene Biguanide on
      Recalcitrant Wounds of Various Etiologies: A Case Series.
AB  - INTRODUCTION: The management of chronic, nonhealing wounds in patients with
      multiple comorbidities continues to be a challenge for health care practitioners.
      Chronic wounds typically do not progress through the normal phases of wound
      healing and generally remain stagnant during the inflammatory phase, resulting in
      an increase in proteolytic enzymes with degradation of the extracellular matrix.
      Bacterial biofilm has been documented to be one of the main factors delaying
      wound healing, resulting in the prolongation of the inflammatory phase.
      OBJECTIVE: In order to control biofilm formation, sequester proteolytic enzymes,
      and provide a biocompatible scaffold to support healing, the investigators
      utilize a purified collagen matrix containing polyhexamethylene biguanide (PCMP)
      in a case series of 9 wounds on 8 patients with multiple comorbidities who did
      not respond to previous conventional or adjuvant therapy. MATERIALS AND METHODS:
      Wound etiologies included 3 pressure ulcers, 1 diabetic foot ulcer, 1 venous leg
      ulcer, 2 postsurgical wound dehiscences, 1 ulcer secondary to calciphylaxis, and
      1 traumatic wound secondary to hematoma. The average wound size at the first PCMP
      application was 34.0 cm2, and the wounds were present for an average of 9.2 weeks
      prior to the first PCMP application. RESULTS: Patients received an average of 5.8
      PCMP applications. Of the 6 wounds that healed, average time to closure from the
      first PCMP application was 10 weeks. The remaining 3 wounds demonstrated improved
      wound appearance with 100% granulation tissue and an average area reduction
      during PCMP treatment of 61.4%. CONCLUSIONS: This case series demonstrated that
      PCMP along with good wound care supported both wound closure and improvements in
      wound bed condition and area reduction on recalcitrant, nonhealing wounds of
      various etiologies.

PMID- 29584604
TI  - Do Not Limit Where Ulcer Debridements Can Be Performed!
AB  - Medicare is a national program administered on a local level by Medicare
      Administrative Contractors (MACs). This brief report focuses on the potentially
      negative outcomes that may ensue as a result of MACs limiting the place of
      service for ulcer debridement. With the information included herein, the hope is
      that this problem can be addressed by all parties involved in wound care,
      including medical directors at these MACs, to remove this limitation impacting
      patient care.

PMID- 29584605
TI  - Evaluating the Impact of a Patient-centered Remote Monitoring Program on
      Adherence to Negative Pressure Wound Therapy.
AB  - : A remote therapy monitoring (RTM) system has been developed for use with a
      negative pressure wound therapy (NPWT) unit for patients in the home care
      setting. In conjunction with RTM, a network of trained professionals call
      patients when their NPWT usage is low and provide education to assist with
      therapy adherence. OBJECTIVE: The objective of this evaluation is to examine the
      relationship between the RTM system and patient adherence. MATERIALS AND METHODS:
      One hundred ninety-eight home care patients receiving NPWT with RTM between
      December 2016 and April 2017 were included. RESULTS: A total of 979 calls were
      made, with an average of 4.9 calls per patient. Among 198 patients, 195 received
      a welcome call, 157 received a call due to low adherence, and 35 had an
      escalation call made to their treating nurse. Of the 157 patients who required at
      least 1 call due to low adherence, 153 were successfully contacted at least once.
      The day following the patient call, adherence increased 73% of the time by an
      average of 8.5 hours. CONCLUSIONS: This evaluation suggests there is an ability
      to influence patient adherence through active engagement, potentially improving
      outcomes and reducing wound costs.

PMID- 29584606
TI  - Hereditary Sensory and Autonomic Neuropathy Presenting With Mutilating Trophic
      Ulcers.
AB  - Two siblings, a 19-year-old woman and an 18-year-old man, born to apparently
      normal parents of second-degree consanguineous marriage, presented to the
      Department of Dermatology, Sawai Man Singh Medical College Hospital, Jaipur,
      India, with recurrent skin ulcers of the hands and feet since early childhood.
      The ulcers were spontaneous, slow to heal, and caused deformities. On initial
      examination, they were found to have distal sensory loss, predominantly to pain
      and temperature. The patients were diagnosed with hereditary sensory and
      autonomic neuropathy of ulceromutilating type (Type 2) based on clinical
      evidences, nerve studies, and neuropathology. Although clinical features were
      distinct, due to slow progression of the disease and lack of clinical suspicion,
      diagnosis was delayed until adulthood when complications developed leading to
      deformities. Through this report, the authors intend to familiarize readers with
      this rare disease that can present with trophic ulcers.

PMID- 29584607
TI  - Calcinosis Cutis and Negative Pressure Wound Therapy as Adjuncts to Surgical
      Management: Case Report and Review of the Literature.
AB  - Calcinosis cutis (CC), or calcium deposition in soft tissue, can cause
      significant morbidity associated with arthralgias and ulceration. This condition
      has an elusive pathophysiology and is often associated with autoimmune disorders,
      significantly impacting the disease burden. The clinical presentation of CC
      varies, and there is no gold standard treatment modality. The case of a 50-year
      old woman with scleroderma and a rare presentation of milky drainage of a left
      hip ulcer secondary to underlying CC that was treated successfully with surgery
      and negative pressure wound therapy is reported herein. Also included is a review
      of the literature of the medical and surgical modalities used in the management
      of this debilitating condition.

PMID- 29584608
TI  - Utilization of a Viable Human Amnion Membrane Allograft in Elderly Patients With
      Chronic Lower Extremity Wounds of Various Etiologies.
AB  - : ntroduction. Chronic nonhealing wounds are a growing health care problem in the
      United States, afflicting more than 6.5 million patients annually. In particular,
      diseases that compromise skin integrity and impair normal wound healing
      processes, such as diabetes and peripheral vascular diseases, are becoming more
      common in the aging population and leading to ever-increasing incidence of these
      chronic nonhealing wounds. OBJECTIVE: The aim of this study is to evaluate a
      viable human amnion membrane allograft (vHAMA) for the treatment of chronic
      nonhealing wounds in elderly patients (aged > 65 years) with multiple
      comorbidities. MATERIALS AND METHODS: Four patients (age range, 69-85 years) with
      5 chronic wounds of varying etiologies and sizes (2 traumatic wounds, 2 diabetic
      foot ulcers, and 1 venous leg ulcer) that persisted for at least 4 weeks and
      failed previous treatment with standard of care were included in this study.
      Comorbidities included diabetes mellitus, obesity, polymyalgia rheumatica,
      lymphedema, peripheral vascular disease, steroid use, and neuropathy. All
      patients received vHAMA once weekly or as deemed appropriate. RESULTS: All
      patients reached complete wound closure with no complications or adverse events.
      Mean time to closure was 4.8 weeks (range, 2-8 weeks) with an average of 4.2
      grafts (range, 1-8). There was no wound recurrence. CONCLUSIONS: Successful
      closure of wounds indicates the use of vHAMA may be beneficial for treatment of
      chronic wounds in elderly patients with comorbidities.

PMID- 29584609
TI  - A Scoping Review of the Use of Silver-impregnated Dressings for the Treatment of
      Chronic Wounds.
AB  - Topical silver agents and dressings are used to control infection and promote
      healing in chronic wounds, but reviews published from 2006 to 2011 found
      heterogeneous results regarding their effectiveness. A scoping review was
      conducted to examine the extent, range, and nature of research activity
      surrounding chronic wound care that employed silver-impregnated dressings;
      identify research gaps in the existing literature; and summarize the evidence to
      provide recommendations for future clinical studies. Ten (10) electronic
      databases and additional sources were screened from their inception to May 2016;
      search terms for the different databases included but were not limited to silver,
      chronic, complications, wound, ulcer, and sore. English-language articles that
      compared silver dressings with an alternate treatment in adults with chronic
      wounds and that reported clinical outcome measures were included. Of 222 full
      text reviewed studies, 27 were included for qualitative analysis. Qualitative
      analysis was guided by key findings identified among the included studies that
      were analyzed in aggregate form where appropriate. In comparative analyses of the
      26 studies that investigated wound healing, 15 revealed significantly positive
      wound healing outcomes with silver treatments versus 9 that did not; the
      remaining 2 failed to provide statistical values of significance. Of 17 studies
      that presented data on microbiology, 3 reported significant microbial load
      improvement for silver dressings, 9 noted nonsignificant findings, and 4 provided
      no statistical values. Pain, adverse events, and treatment cost were included in
      5, 7, and 3 studies, respectively, with heterogeneous findings. The heterogeneous
      evidence regarding the impact of silver dressings on clinical outcomes may be
      related to differences in the silver treatments themselves, heterogeneous
      intervention strategies, study designs, outcomes, and measures. Well-designed
      clinical studies with multiple outcome parameters are necessary to determine the
      optimal type and use of silver-dressings in chronic wounds.

PMID- 29584610
TI  - A Quasi-experimental Study to Explore the Effect of Barrier Cream on the
      Peristomal Skin of Patients With a Tracheostomy.
AB  - Peristomal skin problems represent one of the most common complications of a
      tracheostomy. A quasi-experimental study was conducted among patients ages 18 to
      65 years hospitalized in a Turkish university hospital ear-nose-throat clinic
      between August 15, 2013, and December 15, 2013, to compare the effect of using or
      not using a barrier cream on the peristomal skin with regard to pH, moisture,
      temperature, color, odor, turgor, infections, and lesions after tracheostomy
      surgery. Patients were selected using a purposeful sampling method and included
      if they had not undergone another operation for a complication (eg, pneumothorax,
      tube misplacement, hemorrhage) within 24 hours following the tracheostomy
      operation. In phase 1 of the study, 9 registered nurses were observed 3 times
      each by the researcher, who completed an observation form. From these
      observations and related nursing textbooks, the researcher developed a protocol
      entitled "Nursing Care Steps for Patients with a Tracheostomy." This protocol was
      followed during phase 2 of the study during which participants were alternately
      assigned to either the intervention (a barrier cream containing dimethicone,
      acrylate terpolymer, oils, paraffin, water, dicapryladipate, isopropyl palmitate,
      and PPG-15 stearyl ether followed by gauze) or control (gauze only) group (n = 30
      each) and observed for 7 days. Demographic characteristics were gathered for each
      patient upon admission to the study. Peristomal skin was assessed in terms of pH,
      temperature, and moisture (relative humidity [RH]) using a surface pH meter,
      surface thermometer, and digital skin moisture tester, as well as for lesions,
      infection, and maceration. Findings were documented on a skin condition
      assessment form. Twenty-four (24) hours post surgery, the barrier cream plus
      gauze was applied over peristomal area in the study group and gauze dressing only
      in the control group. Peristomal skin pH, moisture, and temperature were within
      the normal range for both groups during all observations throughout the study but
      closer to normal ranges in the intervention group. Mean peristomal skin pH in the
      intervention group was significantly higher (5.452 +/- 0.043) than in the control
      group (5.123 +/- 0.057; P &.001), mean peristomal skin moisture in the control
      group (46.90 +/- 0.132 RH) was significantly greater than in the intervention
      group (41.71 +/- 0.774 RH; P &.001), and mean peristomal skin temperature in the
      control group (33.59 +/- 1.3 C) was significantly higher than in the intervention
      group (31.64 +/- 0.607 C; P &.001). In both groups, Staphylococcus epidermidis
      was the most commonly cultured microorganism, and S aureus was the most cultured
      pathological microorganism in addition to the normal skin flora. Peristomal skin
      condition was maintained for both the intervention and control groups. Use of a
      barrier cream to protect tracheostomy peristomal skin beneath absorbent dressings
      (eg, gauze) is recommended, but additional short-term and long-term studies are
      needed.

PMID- 29584611
TI  - A Descriptive, Retrospective Study of Using an Oblique Downward-design Gluteus
      Maximus Myocutaneous Flap for Reconstruction of Ischial Pressure Ulcers.
AB  - Despite advances in reconstruction techniques, ischial pressure ulcers continue
      to present a challenge for the plastic surgeon. The purpose of this retrospective
      study was to evaluate outcomes of using an oblique downward gluteus maximus
      myocutaneous (GMM) flap for coverage of grade IV ischial ulcers. Data regarding
      defect size, flap size, operation time, duration of wound healing, and surgical
      outcome were abstracted from the medical records of patients whose ischial
      pressure ulcers had been reconstructed using GMM island flaps between January
      2010 and December 2015. The 22 patients comprised 15 men and 7 women with a mean
      age of 52 (range 16-81) years. Twenty (20) had paraplegia, 6 had a recurrent
      ischial ulcer, 2 were bedridden following a cerebrovascular accident, 1 had a
      myelomeningocele status post operation, and 19 were spinal cord injury patients.
      Follow-up time ranged from 6 to 40 months. Pressure ulcer size ranged from 3 cm x
      2 cm to 10 cm x 5 cm (average 22.3 cm2). The average flap size was 158 cm2 (15.9
      cm x 9.7 cm); the largest was 286 cm2 (22 cm x 13 cm). The operating time ranged
      from 52 minutes to 110 minutes (average, 80 minutes). In 2 cases, wound
      dehiscence occurred but completely healed after resuturing. One (1) ischial
      pressure ulcer recurred 6 months following surgery and was successfully covered
      with a pedicled anterolateral thigh flap. No recurrences or problems were
      observed in the remaining 20 patients. Time to complete wound healing ranged from
      14 to 24 days (average 17.8 days). Treatment of ischial pressure ulcers with GMM
      flaps allowed for an easy, simple procedure that provided the adequate thickness
      of soft tissue needed to cover the bony prominence, fill dead space, and cover
      the lesion. This technique was a reliable and safe reconstructive modality for
      the management of ischial pressure ulcers, even in recurrent cases.

PMID- 29584612
TI  - Elevated serum CA 19-9 with adnexal mass: is it always an ovarian malignancy?
AB  - Endometriotic cysts a common benign gynaecological disease in women of
      reproductive age. We report an unusual case of ruptured endometrioma associated
      with increased CA 19-9. A 27-year-old woman presented with an acute abdomenal
      adnexal mass and elevated CA 19-9. The initial diagnosis of ovarian malignancy
      turned out to be a ruptured endometrioma, confirmed during surgery and in the
      histopathological report.

PMID- 29584613
TI  - Effect of L-carnitine on the skeletal muscle contractility in simvastatin-induced
      myopathy in rats.

PMID- 29584614
TI  - Use of natural products for oral hygiene maintenance: revisiting traditional
      medicine.

PMID- 29584615
TI  - Metabolic and genetic markers' associations with elevated levels of alanine
      aminotransferase in adolescents.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common chronic
      liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity
      and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation
      related genetic markers. The relationship between metabolic or inflammation
      related genetic markers and alanine aminotransferase (ALT) is not fully
      understood. We examined the relationship of MetS, metabolic and inflammation
      related genetic markers with elevated ALT in adolescents. METHODS: A total of 674
      adolescents participated in a cross-sectional study in Guadalajara, Mexico.
      Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International
      Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive
      protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/
      572/-174 haplotype) were evaluated. Multivariate logistic regression was
      performed. RESULTS: Elevated ALT was observed in 3% and 14.1% (total and obese,
      respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence
      interval [95% CI], 1.16-25.89), insulin (OR, 8.51; 95% CI, 2.61-27.71), IR (OR,
      9.10; 95% CI, 2.82-29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25-10.72),
      low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06-8.33), non
      high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27-11.90) and
      IL1RN (OR, 4.64; 95% CI, 1.10-19.53) were associated with elevated ALT. Among
      males, >=2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI,
      1.14-15.71). CONCLUSIONS: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL
      C and IL1RN polymorphism were associated with elevated ALT. Among males, >=2 MetS
      criteria were associated with elevated ALT. There is an urgent need to reduce
      obesity and IR in adolescents to prevent NAFLD.

PMID- 29584616
TI  - Phenotypic presentation of adolescents with overt primary hypothyroidism.
AB  - BACKGROUND: The phenotypic presentation of overt hypothyroidism during
      adolescence is less well characterized. The aim of the study was to study the
      phenotypic presentation of patients with overt hypothyroidism presenting during
      adolescence (age 9-18 years). METHODS: Records of adolescent patients with overt
      hypothyroidism (thyroid stimulating hormone [TSH]>10 mIU/L) were retrospectively
      analyzed for presenting complaints, height and pubertal status. RESULTS: A total
      of 67 patients (40 females and 37 males, average age 13.2+2.3 years) with a mean
      TSH of 241.3+/-336.6 mIU/L were included. The commonest presentation was short
      stature in 46.2% of patients followed by neck swelling (16.4%) and weight gain
      (11.9%). The mean height standard deviation score (SDS) was -2.5+2.11, 43% of
      patients had less than 3 SDS. The height age and bone age were around 3 years
      less than the chronological age. The bone age significantly correlated with the
      height age but not with TSH levels. Three patients referred from neurology with
      primary complaints of headache had pituitary hyperplasia and one presented with
      hypokalemic periodic paralysis. Seven had delayed puberty and one patient had
      early periods due to huge ovarian cysts. CONCLUSIONS: In the present study,
      severe short stature and uncommon phenotypic presentations were a consequence of
      long-standing severe untreated hypothyroidism.

PMID- 29584617
TI  - Constitutively active follicle-stimulating hormone receptor enables androgen
      independent spermatogenesis.
AB  - Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH). This process is considered
      impossible without the absolute requirement of LH-stimulated testicular
      testosterone (T) production. The role of FSH remains unclear because men and mice
      with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the
      role of FSH in spermatogenesis using transgenic mice expressing a constitutively
      strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The
      mutant FSHR reversed the azoospermia and partially restored fertility of Lhr-/-
      mice. The finding was initially ascribed to the residual Leydig cell T
      production. However, when T action was completely blocked with the potent
      antiandrogen flutamide, spermatogenesis persisted. Hence, completely T
      independent spermatogenesis is possible through strong FSHR activation, and the
      dogma of T being a sine qua non for spermatogenesis may need modification. The
      mechanism for the finding appeared to be that FSHR activation maintained the
      expression of Sertoli cell genes considered androgen dependent. The translational
      message of our findings is the possibility of developing a new strategy of high
      dose FSH treatment for spermatogenic failure. Our findings also provide an
      explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs;
      LH/T deficiency with persistent spermatogenesis) and explain how the hormonal
      regulation of spermatogenesis has shifted from FSH to T dominance during
      evolution.

PMID- 29584618
TI  - Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury.
AB  - Loss of bladder control is a challenging outcome facing patients with spinal cord
      injury (SCI). We report that systemic blocking of pro-nerve growth factor
      (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75
      inhibitor resulted in significant improvement in bladder function after SCI in
      rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and
      automatic micturition was acquired weeks earlier than in the controls. The
      improvement was associated with increased excitatory input to the spinal cord, in
      particular onto the tyrosine hydroxylase-positive fibers in the dorsal
      commissure. The drug also had an effect on the bladder itself, as the urothelial
      hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented.
      Urothelial cell loss that precedes hyperplasia was dependent on p75 in response
      to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly,
      death of urothelial cells and the ensuing hyperplastic response were beneficial
      to functional recovery. Deleting p75 from the urothelium prevented urothelial
      death, but resulted in reduction in overall voiding efficiency after SCI. These
      results unveil a dual role of proNGF/p75 signaling in bladder function under
      pathological conditions with a CNS effect overriding the peripheral one.

PMID- 29584619
TI  - PAI1 mediates fibroblast-mast cell interactions in skin fibrosis.
AB  - Fibrosis is a prevalent pathological condition arising from the chronic
      activation of fibroblasts. This activation results from the extensive
      intercellular crosstalk mediated by both soluble factors and direct cell-cell
      connections. Prominent among these are the interactions of fibroblasts with
      immune cells, in which the fibroblast-mast cell connection, although
      acknowledged, is relatively unexplored. We have used a Tg mouse model of skin
      fibrosis, based on expression of the transcription factor Snail in the epidermis,
      to probe the mechanisms regulating mast cell activity and the contribution of
      these cells to this pathology. We have discovered that Snail-expressing
      keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which
      functions as a chemotactic factor to increase mast cell infiltration into the
      skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion
      molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them
      competent to bind to mast cells. This heterotypic cell-cell adhesion, also
      observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal
      activation of both mast cells and fibroblasts, leading to the cascade of events
      that promote fibrogenesis. Thus, we have identified roles for PAI1 in the
      multifactorial program of fibrogenesis that expand its functional repertoire
      beyond its canonical role in plasmin-dependent processes.

PMID- 29584622
TI  - Factors affecting longitudinal changes in cardio-ankle vascular index in a large
      general population: the Nagahama study.
AB  - BACKGROUND: Cardio-ankle vascular index (CAVI) has been increasingly used as an
      index for arterial stiffness. However, the degree of longitudinal changes and
      factors affecting these changes in CAVI (DeltaCAVI) are largely unknown. The aim
      of this study was to descriptively clarify factors associated with longitudinal
      DeltaCAVI for the precise use of this index in the assessment of arterial
      stiffness. METHODS: Study participants comprised 9501 community residents (53.1
      +/- 13.3 years), with 8004 patients included in the longitudinal analysis. CAVI
      was calculated by the transient time interval of arterial waveform measured at
      four extremities. RESULTS: Factors showing a strong association with baseline
      CAVI (7.38 +/- 1.10) included age (beta = 0.586), SBP (beta = 0.175), and male
      sex (beta = 0.142), whereas BMI showed an inverse association (beta = -0.208)
      (all P < 0.001). During the 1815 +/- 135 days follow-up period, CAVI increased by
      0.47 +/- 0.68. Multivariate analysis identified age (beta = 0.508), male sex
      (beta = 0.089), Brinkman index (beta = 0.074), and SBP (beta = 0.037) as positive
      determinants, whereas BMI (beta = -0.079) and baseline CAVI (beta = -0.590) as
      inverse determinants for DeltaCAVI (all P < 0.001). Further data accumulation is
      needed to determine a reference value of CAVI due to its large population
      differences. CONCLUSION: Several factors were commonly associated with baseline
      and longitudinal DeltaCAVI. These factors should be carefully considered when
      CAVI is used for the assessment of arterial stiffness.

PMID- 29584621
TI  - Blocking fatty acid-fueled mROS production within macrophages alleviates acute
      gouty inflammation.
AB  - Gout is the most common inflammatory arthritis affecting men. Acute gouty
      inflammation is triggered by monosodium urate (MSU) crystal deposition in and
      around joints that activates macrophages into a proinflammatory state, resulting
      in neutrophil recruitment. A complete understanding of how MSU crystals activate
      macrophages in vivo has been difficult because of limitations of live imaging
      this process in traditional animal models. By live imaging the macrophage and
      neutrophil response to MSU crystals within an intact host (larval zebrafish), we
      reveal that macrophage activation requires mitochondrial ROS (mROS) generated
      through fatty acid oxidation. This mitochondrial source of ROS contributes to NF
      kappaB-driven production of IL-1beta and TNF-alpha, which promote neutrophil
      recruitment. We demonstrate the therapeutic utility of this discovery by showing
      that this mechanism is conserved in human macrophages and, via pharmacologic
      blockade, that it contributes to neutrophil recruitment in a mouse model of acute
      gouty inflammation. To our knowledge, this study is the first to uncover an
      immunometabolic mechanism of macrophage activation that operates during acute
      gouty inflammation. Targeting this pathway holds promise in the management of
      gout and, potentially, other macrophage-driven diseases.

PMID- 29584620
TI  - JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/beta
      catenin/CCND1 signaling.
AB  - Leukemia-initiating cells (LICs) are responsible for the initiation, development,
      and relapse of leukemia. The identification of novel therapeutic LIC targets is
      critical to curing leukemia. In this report, we reveal that junctional adhesion
      molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis
      is almost completely abrogated upon Jam3 deletion during serial transplantations
      in an MLL-AF9-induced murine acute myeloid leukemia model. In contrast, Jam3
      deletion does not affect the functions of mouse hematopoietic stem cells.
      Moreover, knockdown of JAM3 leads to a dramatic decrease in the proliferation of
      both human leukemia cell lines and primary LICs. JAM3 directly associates with
      LRP5 to activate the downstream PDK1/AKT pathway, followed by the downregulation
      of GSK3beta and activation of beta-catenin/CCND1 signaling, to maintain the self
      renewal ability and cell cycle entry of LICs. Thus, JAM3 may serve as a
      functional LIC marker and play an important role in the maintenance of LIC
      stemness through unexpected LRP5/PDK1/AKT/GSK3beta/beta-catenin/CCND1 signaling
      pathways but not via its canonical role in cell junctions and migration. JAM3 may
      be an ideal therapeutic target for the eradication of LICs without influencing
      normal hematopoiesis.

PMID- 29584623
TI  - Baduanjin Exercise for Stroke Rehabilitation: A Systematic Review with Meta
      Analysis of Randomized Controlled Trials.
AB  - Objective: The purpose of this review was to objectively evaluate the effects of
      Baduanjin exercise on rehabilitative outcomes in stroke patients. Methods: Both
      Chinese and English electronic databases were searched for potentially relevant
      trials. Two review authors independently screened eligible trials against the
      inclusion criteria, extracted data, and assessed the methodological quality by
      using the revised PEDro scale. Meta-analysis was only performed for balance
      function. Results: In total, there were eight randomized controlled trials
      selected in this systematic review. The aggregated result of four trials has
      shown a significant benefit in favor of Baduanjin on balance function (Hedges' g
      = 2.39, 95% CI 2.14 to 2.65, p < 0.001, I2 = 61.54). Additionally, Baduanjin
      exercise effectively improved sensorimotor function of lower extremities and
      ability of daily activities as well as reduced depressive level, leading to
      improved quality of life. Conclusion: Baduanjin exercise as an adjunctive and
      safe method may be conducive to help stroke patients achieve the best possible
      short-term outcome and should be integrated with mainstream rehabilitation
      programs. More rigorous randomized controlled trials with long-term intervention
      periods among a large sample size of stroke patients are needed to draw a firm
      conclusion regarding the rehabilitative effects for this population.

PMID- 29584624
TI  - Sex-Specificity of Oxidative Stress in Newborns Leading to a Personalized
      Antioxidant Nutritive Strategy.
AB  - : Oxidative stress is a critical process that triggers several diseases observed
      in premature infants. Growing recognition of the detriment of oxidative stress in
      newborns warrants the use of an antioxidant strategy that is likely to be
      nutritional in order to restore redox homeostasis. It appears essential to have a
      personalized approach that will take into account the age of gestation at birth
      and the sex of the infant. However, the link between sex and oxidative stress
      remains unclear. The aim of this study was to find a common denominator
      explaining the discrepancy between studies related to sex-specific effects of
      oxidative stress. Results highlight a specificity of sex in the levels of
      oxidative stress markers linked to the metabolism of glutathione, as measured in
      the intracellular compartments. Levels of all sex-dependent oxidative stress
      markers are greater and markers associated to a better antioxidant defense are
      lower in boys compared to girls during the neonatal period. This sex-specific
      discrepancy is likely to be related to estrogen metabolism, which is more active
      in baby-girls and promotes the activation of glutathione metabolism. CONCLUSION:
      our observations suggest that nutritive antioxidant strategies need to target
      glutathione metabolism and, therefore, should be personalized considering, among
      others, the sex specificity.

PMID- 29584625
TI  - Association of Overcrowding and Turnover with Self-Harm in a Swiss Pre-Trial
      Prison.
AB  - Self-harm is a common issue in detention and includes both suicidal and non
      suicidal behaviours. Beyond well-known individual risk factors, institutional
      factors such as overcrowding (i.e., when the prison population exceeds its
      capacity) and turnover (i.e., the rate at which the prison population is
      renewed), may also increase the risk of self-harm. However, these factors are
      understudied or previous studies reported inconsistent findings. This study
      investigated the association of self-harm with overcrowding and turnover in the
      largest pre-trial Swiss prison in Geneva. Data were collected yearly between 2011
      and 2017. Measures included self-harm (all kinds of self-injuring acts requiring
      medical attention, including self-strangulations and self-hangings). We performed
      meta-regressions to analyse the relationships between self-harm and institutional
      factors. Self-harm events were frequent, with a prevalence estimate of 26.4%.
      Overcrowding and turnover were high (average occupation rate of 177% and average
      turnover of 73%, respectively). Overcrowding and turnover were significantly
      associated with self-harm (respectively b = 0.068, p < 0.001 and (b = 1.257, p <
      0.001). In both cases, self-harm was higher when overcrowding and turnover
      increased. Overcrowding and turnover raise important human rights concerns and
      have damaging effects on the health of people living in detention. Identification
      of and care for this vulnerable population at risk of self-harm are needed and
      institutional factors should be addressed.

PMID- 29584626
TI  - Characterization of Fine Particulate Matter and Associated Health Burden in
      Nanjing.
AB  - Particulate matter (PM) air pollution has become a serious environmental problem
      in Nanjing and poses great health risks to local residents. In this study,
      characteristics of particulate matter with an aerodynamic diameter less than 2.5
      MUm (PM2.5) over Nanjing were analyzed using hourly and daily averaged PM2.5
      concentrations and meteorological parameters collected from nine national
      monitoring sites during the period of March 2014 to February 2017. Then, the
      integrated exposure-response (IER) model was applied to assess premature
      mortality, years of life lost (YLL) attributable to PM2.5, and mortality benefits
      due to PM2.5 reductions. The concentrations of PM2.5 varied among hours, seasons
      and years, which can be explained by differences in emission sources, secondary
      formations and meteorological conditions. The decreased ratio of PM2.5 to CO
      suggested that secondary contributions decreased while the relative contributions
      of vehicle exhaust increased from increased CO data. According to the values of
      attributable fractions (AF), stroke was the major cause of death, followed by
      ischemic heart disease (IHD), lung cancer (LC) and chronic obstructive pulmonary
      disease (COPD). The estimated total deaths in Nanjing due to PM2.5 were 12,055
      and 10,771, leading to 98,802 and 87,647 years of life lost in 2014 and 2015,
      respectively. The elderly and males had higher health risks than youngsters and
      females. When the PM2.5 concentrations meet the World Health Organization (WHO)
      Air Quality Guidelines (AQG) of 10 MUg/m3, 84% of the premature deaths would be
      avoided, indicating that the Nanjing government needs to adopt more stringent
      measure to reduce PM pollution and enhance the health benefits.

PMID- 29584628
TI  - Evaluation of Loss Due to Storm Surge Disasters in China Based on Econometric
      Model Groups.
AB  - Storm surge has become an important factor restricting the economic and social
      development of China's coastal regions. In order to improve the scientific
      judgment of future storm surge damage, a method of model groups is proposed to
      refine the evaluation of the loss due to storm surges. Due to the relative
      dispersion and poor regularity of the natural property data (login center air
      pressure, maximum wind speed, maximum storm water, super warning water level,
      etc.), storm surge disaster is divided based on eight kinds of storm surge
      disaster grade division methods combined with storm surge water, hypervigilance
      tide level, and disaster loss. The storm surge disaster loss measurement model
      groups consist of eight equations, and six major modules are constructed: storm
      surge disaster in agricultural loss, fishery loss, human resource loss,
      engineering facility loss, living facility loss, and direct economic loss.
      Finally, the support vector machine (SVM) model is used to evaluate the loss and
      the intra-sample prediction. It is indicated that the equations of the model
      groups can reflect in detail the relationship between the damage of storm surges
      and other related variables. Based on a comparison of the original value and the
      predicted value error, the model groups pass the test, providing scientific
      support and a decision basis for the early layout of disaster prevention and
      mitigation.

PMID- 29584627
TI  - Multi-Scale Clustering of Lyme Disease Risk at the Expanding Leading Edge of the
      Range of Ixodes scapularis in Canada.
AB  - Since its detection in Canada in the early 1990s, Ixodes scapularis, the primary
      tick vector of Lyme disease in eastern North America, has continued to expand
      northward. Estimates of the tick's broad-scale distribution are useful for
      tracking the extent of the Lyme disease risk zone; however, tick distribution may
      vary widely within this zone. Here, we investigated I. scapularis nymph
      distribution at three spatial scales across the Lyme disease emergence zone in
      southern Quebec, Canada. We collected ticks and compared the nymph densities
      among different woodlands and different plots and transects within the same
      woodland. Hot spot analysis highlighted significant nymph clustering at each
      spatial scale. In regression models, nymph abundance was associated with litter
      depth, humidity, and elevation, which contribute to a suitable habitat for ticks,
      but also with the distance from the trail and the type of trail, which could be
      linked to host distribution and human disturbance. Accounting for this
      heterogeneous nymph distribution at a fine spatial scale could help improve Lyme
      disease management strategies but also help people to understand the risk
      variation around them and to adopt appropriate behaviors, such as staying on the
      trail in infested parks to limit their exposure to the vector and associated
      pathogens.

PMID- 29584629
TI  - Co-Culture with Human Osteoblasts and Exposure to Extremely Low Frequency Pulsed
      Electromagnetic Fields Improve Osteogenic Differentiation of Human Adipose
      Derived Mesenchymal Stem Cells.
AB  - Human adipose-derived mesenchymal stem cells (Ad-MSCs) have been proposed as
      suitable option for cell-based therapies to support bone regeneration. In the
      bone environment, Ad-MSCs will receive stimuli from resident cells that may favor
      their osteogenic differentiation. There is recent evidence that this process can
      be further improved by extremely low frequency pulsed electromagnetic fields (ELF
      PEMFs). Thus, the project aimed at (i) investigating whether co-culture
      conditions of human osteoblasts (OBs) and Ad-MSCs have an impact on their
      proliferation and osteogenic differentiation; (ii) whether this effect can be
      further improved by repetitive exposure to two specific ELF-PEMFs (16 and 26 Hz);
      (iii) and the effect of these ELF-PEMFs on human osteoclasts (OCs). Osteogenic
      differentiation was improved by co-culturing OBs and Ad-MSCs when compared to the
      individual mono-cultures. An OB to Ad-MSC ratio of 3:1 had best effects on total
      protein content, alkaline phosphatase (AP) activity, and matrix mineralization.
      Osteogenic differentiation was further improved by both ELF-PEMFs investigated.
      Interestingly, only repetitive exposure to 26 Hz ELF-PEMF increased Trap5B
      activity in OCs. Considering this result, a treatment with gradually increasing
      frequency might be of interest, as the lower frequency (16 Hz) could enhance bone
      formation, while the higher frequency (26 Hz) could enhance bone remodeling.

PMID- 29584630
TI  - Gut Microbiota and Type 1 Diabetes.
AB  - Recently, the onset of type 1 diabetes (T1D) has increased rapidly and became a
      major public health concern worldwide. Various factors are associated with the
      development of T1D, such as diet, genome, and intestinal microbiota. The
      gastrointestinal (GI) tract harbors a complex and dynamic population of
      microorganisms, the gut microbiota, which exert a marked influence on the host
      homeostasis and metabolic diseases. Recent evidence shows that altered gut
      bacterial composition (dysbiosis) is highly associated with the pathogenesis of
      insulin dysfunction and T1D and, thus, targeting gut microbiota may serve as a
      therapeutic potential for T1D patients. In this study, we updated the effect of
      gut microbiota on T1D and potential mechanisms were discussed.

PMID- 29584631
TI  - Future Orientation among Students Exposed to School Bullying and Cyberbullying
      Victimization.
AB  - Future orientation can be defined as an individual's thoughts, beliefs, plans,
      and hopes for the future. Earlier research has shown adolescents' future
      orientation to predict outcomes later in life, which makes it relevant to analyze
      differences in future orientation among youth. The aim of the present study was
      to analyze if bullying victimization was associated with an increased likelihood
      of reporting a pessimistic future orientation among school youth. To be able to
      distinguish between victims and bully-victims (i.e., students who are both
      bullies and victims), we also took perpetration into account. The data were
      derived from the Stockholm School Survey performed in 2016 among ninth grade
      students (ages 15-16 years) (n = 5144). Future orientation and involvement in
      school bullying and in cyberbullying were based on self-reports. The statistical
      method used was binary logistic regression. The results demonstrated that victims
      and bully-victims of school bullying and of cyberbullying were more likely to
      report a pessimistic future orientation compared with students not involved in
      bullying. These associations were shown also when involvement in school bullying
      and cyberbullying were mutually adjusted. The findings underline the importance
      of anti-bullying measures that target both school bullying and cyberbullying.

PMID- 29584632
TI  - Inhibition of Zika Virus Replication by Silvestrol.
AB  - The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic
      outcomes highlighted the need for new antiviral substances with broad-spectrum
      activities to react quickly to unexpected outbreaks of emerging viral pathogens.
      Very recently, the natural compound silvestrol isolated from the plant Aglaia
      foveolata was found to have very potent antiviral effects against the (-)-strand
      RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)
      strand RNA-genome. This antiviral activity is based on the impaired translation
      of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation
      factor-4A (eIF4A) which is required to unwind structured 5'-untranslated regions
      (5'-UTRs) of several proto-oncogenes and thereby facilitate their translation.
      Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5'
      capped UTR with distinct secondary structure elements. Therefore, we investigated
      the effects of silvestrol on ZIKV replication in A549 cells and primary human
      hepatocytes. Two different ZIKV strains were used. In both infected A549 cells
      and primary human hepatocytes, silvestrol has the potential to exert a
      significant inhibition of ZIKV replication for both analyzed strains, even though
      the ancestor strain from Uganda is less sensitive to silvestrol. Our data might
      contribute to identify host factors involved in the control of ZIKV infection and
      help to develop antiviral concepts that can be used to treat a variety of viral
      infections without the risk of resistances because a host protein is targeted.

PMID- 29584633
TI  - Temperature and Vibration Dependence of the Faraday Effect of Gd2O3 NPs-Doped
      Alumino-Silicate Glass Optical Fiber.
AB  - All-optical fiber magnetic field sensor based on the Gd2O3 nano-particles (NPs)
      doped alumino-silicate glass optical fiber was developed, and its temperature and
      vibration dependence on the Faraday Effect were investigated. Uniformly embedded
      Gd2O3 NPs were identified to form in the core of the fiber, and the measured
      absorption peaks of the fiber appearing at 377 nm, 443 nm, and 551 nm were
      attributed to the Gd2O3 NPs incorporated in the fiber core. The Faraday rotation
      angle (FRA) of the linearly polarized light was measured at 650 nm with the
      induced magnetic field by the solenoid. The Faraday rotation angle was found to
      increase linearly with the magnetic field, and it was about 18.16 degrees  +/-
      0.048 degrees  at 0.142 Tesla (T) at temperatures of 25  degrees C-120  degrees
      C, by which the estimated Verdet constant was 3.19 rad/(T?m) +/- 0.01 rad/(T?m).
      The variation of the FRA with time at 0.142 T and 120  degrees C was negligibly
      small (-9.78 * 10-4  degrees /min). The variation of the FRA under the mechanical
      vibration with the acceleration below 10 g and the frequency above 50 Hz was
      within 0.5 degrees .

PMID- 29584634
TI  - Printing and Folding: A Solution for High-Throughput Processing of Organic Thin
      Film Thermoelectric Devices.
AB  - Wearable electronics are rapidly expanding, especially in applications like
      health monitoring through medical sensors and body area networks (BANs).
      Thermoelectric generators (TEGs) have been the main candidate among the different
      types of energy harvesting methods for body-mounted or even implantable sensors.
      Introducing new semiconductor materials like organic thermoelectric materials and
      advancing manufacturing techniques are paving the way to overcome the barriers
      associated with the bulky and inflexible nature of the common TEGs and are making
      it possible to fabricate flexible and biocompatible modules. Yet, the lower
      efficiency of these materials in comparison with bulk-inorganic counterparts as
      well as applying them mostly in the form of thin layers on flexible substrates
      limits their applications. This research aims to improve the functionality of
      thin and flexible organic thermoelectric generators (OTEs) by utilizing a novel
      design concept inspired by origami. The effects of critical geometric parameters
      are investigated using COMSOL Multiphysics to further prove the concept of
      printing and folding as an approach for the system level optimization of printed
      thin film TEGs.

PMID- 29584635
TI  - The Synthesis of Molecular Docking Studies, In Vitro Antimicrobial and Antifungal
      Activities of Novel Dipeptide Derivatives Based on N-(2-(2-Hydrazinyl-2
      oxoethylamino)-2-oxoethyl)-nicotinamide.
AB  - A series of linear dipeptide derivatives (4-10) were prepared and evaluated as
      antimicrobial agents via the synthesis of N-(2-(2-hydrazinyl-2-oxoethylamino)-2
      oxoethyl) nicotinamide (4). Compound 4 was reacted with 4-chlorobenzaldehyde or 4
      hydroxybenzaldehyde, to give the hydrazones 5 and 6, respectively. On the other
      hand, Compound 4 was coupled with phenylisocyanate or methylisothiocyanate to
      give Compounds 7 and 8, respectively. The latter compounds (7 and 8) were coupled
      with chloroacetic acid to give oxazolidine (9) and thiazolidine (10),
      respectively. The newly synthesized dipeptide compounds were confirmed by means
      of their spectral data. The antimicrobial activity of the newly synthesized
      compounds 4-10 was evaluated by agar well diffusion, and they showed good
      activity. Compounds 4, 5, and 9 gave the most promising activity in this study.
      Most of the tested compounds possessed MIC values ranging from 50 to 500 ug/mL.
      Furthermore, docking studies were carried out on enoyl reductase from E. coli and
      cytochrome P450 14 alpha-sterol demethylase (Cyp51) from Candida albicans active
      sites. The MolDock scores of the seven tested compounds ranged between -117 and 
      171 and between -107 and -179, respectively.

PMID- 29584636
TI  - Response of Plant Secondary Metabolites to Environmental Factors.
AB  - Plant secondary metabolites (SMs) are not only a useful array of natural products
      but also an important part of plant defense system against pathogenic attacks and
      environmental stresses. With remarkable biological activities, plant SMs are
      increasingly used as medicine ingredients and food additives for therapeutic,
      aromatic and culinary purposes. Various genetic, ontogenic, morphogenetic and
      environmental factors can influence the biosynthesis and accumulation of SMs.
      According to the literature reports, for example, SMs accumulation is strongly
      dependent on a variety of environmental factors such as light, temperature, soil
      water, soil fertility and salinity, and for most plants, a change in an
      individual factor may alter the content of SMs even if other factors remain
      constant. Here, we review with emphasis how each of single factors to affect the
      accumulation of plant secondary metabolites, and conduct a comparative analysis
      of relevant natural products in the stressed and unstressed plants. Expectantly,
      this documentary review will outline a general picture of environmental factors
      responsible for fluctuation in plant SMs, provide a practical way to obtain
      consistent quality and high quantity of bioactive compounds in vegetation, and
      present some suggestions for future research and development.

PMID- 29584637
TI  - Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV
      Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction
      Efficiency of Derived Vectors.
AB  - Single nucleotide changes were introduced into the non-structural (NS) coding
      sequence of the H-1 parvovirus (PV) infectious molecular clone and the
      corresponding virus stocks produced, thereby generating H1-PM-I, H1-PM-II, H1-PM
      III, and H1-DM. The effects of the mutations on viral fitness were analyzed.
      Because of the overlapping sequences of NS1 and NS2, the mutations affected
      either NS2 (H1-PM-II, -III) or both NS1 and NS2 proteins (H1-PM-I, H1-DM). Our
      results show key benefits of PM-I, PM-II, and DM mutations with regard to the
      fitness of the virus stocks produced. Indeed, these mutants displayed a higher
      production of infectious virus in different cell cultures and better spreading
      capacity than the wild-type virus. This correlated with a decreased particle-to
      infectivity (P/I) ratio and stimulation of an early step(s) of the viral cycle
      prior to viral DNA replication, namely, cell binding and internalization. These
      mutations also enhance the transduction efficiency of H-1PV-based vectors. In
      contrast, the PM-III mutation, which affects NS2 at a position downstream of the
      sequence deleted in Del H-1PV, impaired virus replication and spreading. We
      hypothesize that the NS2 protein-modified in H1-PM-I, H1-PM-II, and H1-DM-may
      result in the stimulation of some maturation step(s) of the capsid and facilitate
      virus entry into subsequently infected cells.

PMID- 29584638
TI  - Electronic Detection of DNA Hybridization by Coupling Organic Field-Effect
      Transistor-Based Sensors and Hairpin-Shaped Probes.
AB  - In this paper, the electronic transduction of DNA hybridization is presented by
      coupling organic charge-modulated field-effect transistors (OCMFETs) and hairpin
      shaped probes. These probes have shown interesting properties in terms of
      sensitivity and selectivity in other kinds of assays, in the form of molecular
      beacons (MBs). Their integration with organic-transistor based sensors, never
      explored before, paves the way to a new class of low-cost, easy-to-use, and
      portable genetic sensors with enhanced performances. Thanks to the peculiar
      characteristics of the employed sensor, measurements can be performed at
      relatively high ionic strengths, thus optimizing the probes' functionality
      without affecting the detection ability of the device. A complete electrical
      characterization of the sensor is reported, including calibration with different
      target concentrations in the measurement environment and selectivity evaluation.
      In particular, DNA hybridization detection for target concentration as low as 100
      pM is demonstrated.

PMID- 29584639
TI  - Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi
      3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable
      Alternative towards Novel Aza-Analogues of Falipamil.
AB  - We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4
      b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N
      acylation/aromatization) in 20 to 95% overall yields, as well as four
      pharmacologically promising analogues via an improved cascade process (Ugi
      3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked
      pyrrolo[3,4-b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza
      analogues in 30 and 35% overall yields. It is worth highlighting the good
      substrate scope found, because final products are furnished with alkyl, aryl, and
      heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as
      key reagents for the Ugi-type three component reaction) allowed for a rapid and
      efficient assembly of the polysubstituted oxindoles, which were used in situ
      toward the complex products, conferring features like robustness, sustainability,
      and the one-pot approach to this synthetic methodology.

PMID- 29584640
TI  - GreenshellTM Mussels: A Review of Veterinary Trials and Future Research
      Directions.
AB  - The therapeutic benefits of GreenshellTM mussel (GSM; Perna canaliculus)
      preparations have been studied using in vitro test systems, animal models, and
      human clinical trials focusing mainly on anti-inflammatory and anti-arthritic
      effects. Activity is thought to be linked to key active ingredients that include
      omega-3 polyunsaturated fatty acids, a variety of carotenoids and other bioactive
      compounds. In this paper, we review the studies that have been undertaken in
      dogs, cats, and horses, and outline new research directions in shellfish breeding
      and high-value nutrition research programmes targeted at enhancing the efficacy
      of mussel and algal extracts. The addition of GSM to animal diets has alleviated
      feline degenerative joint disease and arthritis symptoms, and chronic orthopaedic
      pain in dogs. In horses, GSM extracts decreased the severity of lameness and
      joint pain and provided improved joint flexion in limbs with lameness attributed
      to osteoarthritis. Future research in this area should focus on elucidating the
      key active ingredients in order to link concentrations of these active
      ingredients with their pharmacokinetics and therapeutic effects. This would
      enable consistent and improved efficacy from GSM-based products for the purpose
      of improved animal health.

PMID- 29584641
TI  - Tri-Ponderal Mass Index vs. Fat Mass/Height3 as a Screening Tool for Metabolic
      Syndrome Prediction in Colombian Children and Young People.
AB  - Tri-ponderal mass index (TMI) and fat mass index (FMI) have been proposed as
      alternative approaches for assessing body fat since BMI does not ensure an
      accurate screening for obesity and overweight status in children and adolescents.
      This study proposes thresholds of the TMI and FMI for the prediction of metabolic
      syndrome (MetS) in children and young people. For this purpose, a cross-sectional
      study was conducted on 4673 participants (57.1% females), who were 9-25 years of
      age. As part of the study, measurements of the subjects' weight, waist
      circumference, serum lipid indices, blood pressure and fasting plasma glucose
      were taken. Body composition was measured by bioelectrical impedance analysis
      (BIA). The TMI and FMI were calculated as weight (kg)/height (m3) and fat mass
      (kg)/height (m3), respectively. Following the International Diabetes Federation
      (IDF) definition, MetS is defined as including three or more metabolic
      abnormalities. Cohort-specific thresholds were established to identify Colombian
      children and young people at high risk of MetS. The thresholds were applied to
      the following groups: (i) a cohort of children where the girls' TMI >= 12.13
      kg/m3 and the boys' TMI >= 12.10 kg/m3; (ii) a cohort of adolescents where the
      girls' TMI >= 12.48 kg/m3 and the boys' TMI >= 11.19 kg/m3; (iii) a cohort of
      young adults where the women's TMI >= 13.21 kg/m3 and the men's TMI >= 12.19
      kg/m3. The FMI reference cut-off values used for the different groups were as
      follows: (i) a cohort of children where the girls' FMI >= 2.59 fat mass/m3 and
      the boys' FMI >= 1.98 fat mass/m3; (ii) a cohort of adolescents where the girls'
      FMI >= 3.12 fat mass/m3 and the boys' FMI >= 1.46 fat mass/m3; (iii) a cohort of
      adults where the women's FMI >= 3.27 kg/m3 and the men's FMI >= 1.65 kg/m3. Our
      results showed that the FMI and TMI had a moderate discriminatory power to detect
      MetS in Colombian children, adolescents, and young adults.

PMID- 29584642
TI  - A Visible Light-Driven Minisci-Type Reaction with N-Hydroxyphthalimide Esters.
AB  - A visible light-promoted protocol for the redox-neutral coupling of N
      hydroxyphthalimide esters with different N-heterocyclic compounds is described.
      The reaction proceeds through an alkyl radical intermediate generated by
      reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the
      original Minisci protocol, polyalkylation can largely be avoided. Mechanistic
      investigations revealed a radical chain mechanism which in some cases can proceed
      even if no photocatalyst is added. This valuable and functional group-tolerant
      reaction produces substituted heterocycles in moderate to excellent yield. The
      use of inexpensive starting materials and LEDs as the light source are key
      features of this C-C bond formation.

PMID- 29584643
TI  - Antibacterial Activity of Orthodontic Cement Containing Quaternary Ammonium
      Polyethylenimine Nanoparticles Adjacent to Orthodontic Brackets.
AB  - Enamel demineralization is a common problem found in patients using orthodontic
      devices, such as orthodontic braces. It was found that Streptoccocus mutans
      growth increases adjacent to orthodontic devices, which may result in caries
      development. Incorporated antibacterial quaternary ammonium polyethylenimine
      (QPEI) nanoparticles were previously shown to be highly efficacious against
      various bacteria. Combining antibacterial materials in orthodontic cement may be
      advantageous to prevent bacterial outgrowth adjacent to orthodontic brackets. The
      aim was to evaluate the efficiency of orthodontic cement containing QPEI
      nanoparticles in reducing S. mutans and Lactobacillus casei outgrowth adjacent to
      orthodontic brackets. Orthodontic brackets were bonded to the buccal surfaces of
      extracted lower incisors. The antibacterial effect on S. mutans and L. casei
      outgrowth of Neobond bracket adhesive orthodontic cement with and without QPEI
      nanoparticles was compared. The antibacterial effect was evaluated using crystal
      violet staining and bacterial count (CFU/mL). The teeth in the experimental
      group, with the QPEI nanoparticles cement, showed significantly lower optical
      density (OD) values and CFU counts of S. mutans and L. casei than the teeth in
      the control group (p < 0.05). Based on the results, it can be concluded that
      orthodontic cement containing QPEI nanoparticles significantly inhibits S. mutans
      and L. casei growth around orthodontic brackets.

PMID- 29584645
TI  - An Improved Positioning Method for Two Base Stations in AIS.
AB  - Resilient position, navigation, and timing (PNT) data is indispensable
      information in the field of e-navigation. An automatic identification system
      (AIS) based ranging mode (R-Mode) is put forward to develop a terrestrial backup
      system in order to overcome the vulnerability of the global navigation satellite
      system (GNSS). In general, at least three base stations are required in the
      traditional R-Mode positioning method. However, the geometric distribution of
      existing base stations is not considered for positioning, as AIS is a
      communication system. In some cases, a vessel can only receive signals from two
      base stations. In this paper, an improved position estimation method based on
      displacement correction is therefore proposed to solve this problem. Compared
      with the prior displacement correction position estimation (DCPE) method, the
      proposed method can improve positioning accuracy effectively by adopting a more
      precise motion model for the vessel, including an accelerated motion and a
      turning motion model. Moreover, the motion model is employed adaptively to
      correct the displacement of the vessel. Finally, the proposed method is verified
      and the performance is analyzed and compared by simulation. This study can extend
      the application region of AIS R-Mode.

PMID- 29584644
TI  - On Your Own: Older Adults' Food Choice and Dietary Habits.
AB  - The United Kingdom, in common with many countries, has an ageing demographic.
      Changes accompanying ageing can influence food choice and dietary habits. This
      study explored older adults' perceptions and practices related to dietary
      behaviour and the factors influencing their food choice in later life. Semi
      structured focus-group discussions were conducted with 30 individuals (aged 63-90
      years) in a UK city. An inductive thematic approach was adopted for data
      analysis, and 4 themes and 12 sub-themes emerged: age-related changes (lower
      appetite, food changes, declining physical function); food access (food cost,
      support with food, maintaining independence); on your own (cooking for one,
      eating alone, shopping for one); and relationship with food (food variety, eating
      what you want, dieting). These influenced participants' food acquisition, food
      preparation and cooking, as well as eating habits. Living alone and its
      substantial influence, as well as associated social isolation and loneliness,
      were highlighted in many of the discussions. Given the possible implications for
      nutritional intake, further work is recommended in this area. Likewise, steps
      should be taken to improve food access, increase opportunities for commensal
      eating and, fundamentally, address social isolation and loneliness in the older
      population.

PMID- 29584646
TI  - Oleylamine-Mediated Hydrothermal Growth of Millimeter-Long Cu Nanowires and Their
      Electrocatalytic Activity for Reduction of Nitrate.
AB  - While high-aspect-ratio metal nanowires are essential for producing nanowire
      based electrodes of good performance used in electronics and electrocatalysis,
      the synthesis of millimeter-long Cu nanowires remains a challenge. This work
      demonstrates an oleylamine-mediated hydrothermal method for synthesis of Cu
      nanowires with an average diameter of ~80 nm and a length up to several
      millimeters. An investigation on the role of oleylamine in nanowire formation by
      mass spectroscopy, small angle X-ray diffraction and transmission electron
      microscopy reveals that oleylamine serves as a mild reducing agent for slow
      reduction of Cu(II) to Cu, a complexing agent to form Cu(II)-oleylamine complex
      for guiding the nanowire growth, as well as a surfactant to generate lamellar
      phase structure for the formation of nanowire bundles. The growth mechanism of
      these millimeter-long Cu nanowire bundles is proposed based on the experimental
      observations. Electrochemical measurements by linear sweep voltammetry indicate
      that the self-supported nanowire electrode prepared from as-formed Cu nanowire
      bundles shows high catalytic activity for electroreduction of nitrate in water.

PMID- 29584647
TI  - FEM Modeling of In-Plane Stress Distribution in Thick Brittle Coatings/Films on
      Ductile Substrates Subjected to Tensile Stress to Determine Interfacial Strength.
AB  - The ceramic-metal interface is present in various material structures and devices
      that are vulnerable to failures, like cracking, which are typically due to their
      incompatible properties, e.g., thermal expansion mismatch. In failure of these
      multilayer systems, interfacial shear strength is a good measure of the
      robustness of interfaces, especially for planar films. There is a widely-used
      shear lag model and method by Agrawal and Raj to analyse and measure the
      interfacial shear strength of thin brittle film on ductile substrates. The use of
      this classical model for a type of polymer derived ceramic coatings (thickness
      ~18 MUm) on steel substrate leads to high values of interfacial shear strength.
      Here, we present finite element simulations for such a coating system when it is
      subjected to in-plane tension. Results show that the in-plane stresses in the
      coating are non-uniform, i.e., varying across the thickness of the film.
      Therefore, they do not meet one of the basic assumptions of the classical model:
      uniform in-plane stress. Furthermore, effects of three significant parameters,
      film thickness, crack spacing, and Young's modulus, on the in-plane stress
      distribution have also been investigated. 'Thickness-averaged In-plane Stress'
      (TIS), a new failure criterion, is proposed for estimating the interfacial shear
      strength, which leads to a more realistic estimation of the tensile strength and
      interfacial shear strength of thick brittle films/coatings on ductile substrates.

PMID- 29584648
TI  - The Nothoaspis amazoniensis Complete Mitogenome: A Comparative and Phylogenetic
      Analysis.
AB  - The molecular biology era, together with morphology, molecular phylogenetics,
      bioinformatics, and high-throughput sequencing technologies, improved the
      taxonomic identification of Argasidae family members, especially when considering
      specimens at different development stages, which remains a great difficulty for
      acarologists. These tools could provide important data and insights on the
      history and evolutionary relationships of argasids. To better understand these
      relationships, we sequenced and assembled the first complete mitochondrial genome
      of Nothoaspis amazoniensis. We used phylogenomics to identify the evolutionary
      history of this species of tick, comparing the data obtained with 26 complete
      mitochondrial sequences available in biological databases. The results
      demonstrated the absence of genetic rearrangements, high similarity and identity,
      and a close organizational link between the mitogenomes of N. amazoniensis and
      other argasids analyzed. In addition, the mitogenome had a monophyletic cladistic
      taxonomic arrangement, encompassed by representatives of the Afrotropical and
      Neotropical regions, with specific parasitism in bats, which may be indicative of
      an evolutionary process of cospeciation between vectors and the host.

PMID- 29584649
TI  - Lee, J.E. et al. Ethanol Extract of Oldenlandia diffusa Herba Attenuates
      Scopolamine-Induced Cognitive Impairments in Mice via Activation of BDNF, P-CREB
      and Inhibition of Acetylcholinesterase.
AB  - The authors wish to make the following corrections to this paper [1].[...].

PMID- 29584650
TI  - Identification of a Novel Recombinant Type 2 Porcine Reproductive and Respiratory
      Syndrome Virus in China.
AB  - Since the emergence of NADC30-like porcine reproductive and respiratory syndrome
      virus (PRRSV) in China in 2013, PRRSVs have undergone rapid evolution. In this
      study, a novel variant of PRRSV strain (designated SCcd17) was successfully
      isolated from piglets with clinical signs in Sichuan Province in China in 2017,
      and the complete genomic sequence was determined. The genome of this new isolate
      was 15,015 nucleotides (nt) long, and comparative analysis revealed that SCcd17
      exhibited 90.2%, 85.2%, 84.9%, and 84.0% nucleotide similarity to PRRSVs NADC30,
      JXA1, CH-1a, and VR-2332, respectively. Phylogenetic analysis indicated that the
      SCcd17 strain was classified into the NADC30-like sub-genotype, in which all the
      strains contained the unique discontinuous 131-amino acid deletion in
      nonstructural protein 2 (nsp2) when compared to VR-2332-like viruses. Notably,
      extensive amino acid substitutions were observed in nsp2 and a unique single
      amino acid deletion at position 33 of the GP5 is being described for the first
      time. Strikingly, recombination analysis revealed that SCcd17 was the result of
      recombination between the NADC30-like, JXA1-like, and VR-2332-like strains at
      five recombination breakpoints: nsp1alpha (nt 641), nsp3 (nt 5141), nsp10 (nt
      9521), open reading frame 3 (ORF3) (nt 12,581), and ORF4 (nt 13,021). The genomic
      data of SCcd17 will be helpful for understanding the role of genomic
      recombination in the evolution of PRRSV.

PMID- 29584651
TI  - Molecular Binding Contributes to Concentration Dependent Acrolein Deposition in
      Rat Upper Airways: CFD and Molecular Dynamics Analyses.
AB  - Existing in vivo experiments show significantly decreased acrolein uptake in rats
      with increasing inhaled acrolein concentrations. Considering that high-polarity
      chemicals are prone to bond with each other, it is hypothesized that molecular
      binding between acrolein and water will contribute to the experimentally observed
      deposition decrease by decreasing the effective diffusivity. The objective of
      this study is to quantify the probability of molecular binding for acrolein, as
      well as its effects on acrolein deposition, using multiscale simulations. An
      image-based rat airway geometry was used to predict the transport and deposition
      of acrolein using the chemical species model. The low Reynolds number turbulence
      model was used to simulate the airflows. Molecular dynamic (MD) simulations were
      used to study the molecular binding of acrolein in different media and at
      different acrolein concentrations. MD results show that significant molecular
      binding can happen between acrolein and water molecules in human and rat airways.
      With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds
      contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed
      favorably with previous MD results. The percentage of hydrogen-bonded acrolein
      compounds is higher at higher acrolein concentrations or in a medium with higher
      polarity. Computational dosimetry results show that the size increase caused by
      the molecular binding reduces the effective diffusivity of acrolein and lowers
      the chemical deposition onto the airway surfaces. This result is consistent with
      the experimentally observed deposition decrease at higher concentrations.
      However, this size increase can only explain part of the concentration-dependent
      variation of the acrolein uptake and acts as a concurrent mechanism with the
      uptake-limiting tissue ration rate. Intermolecular interactions and associated
      variation in diffusivity should be considered in future dosimetry modeling of
      high-polarity chemicals such as acrolein.

PMID- 29584652
TI  - Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola
      Virus Entry Inhibitor.
AB  - The recent 2014-2016 West African Ebola virus epidemic underscores the need for
      the development of novel anti-Ebola therapeutics, due to the high mortality rates
      of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is
      available for the prevention and treatment. Traditional Chinese medicines (TCMs)
      represent a huge reservoir of bioactive chemicals and many TCMs have been shown
      to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a
      high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract
      of Rhodiola rosea displayed specific and potent inhibition against cell entry of
      both Ebola virus and Marburg virus. In addition, twenty commercial compounds that
      were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola
      virus entry assay, and it was found that ellagic acid and gallic acid, which are
      two structurally related compounds, are the most effective ones. The activity of
      the extract and the two pure compounds were validated using infectious Ebola
      virus. The time-of-addition experiments suggest that, mechanistically, the
      Rhodiola rosea extract and the effective compounds act at an early step in the
      infection cycle following initial cell attachment, but prior to viral/cell
      membrane fusion. Our findings provide evidence that Rhodiola rosea has potent
      anti-filovirus properties that may be developed as a novel anti-Ebola treatment.

PMID- 29584653
TI  - Geometrically Nonlinear Field Fracture Mechanics and Crack Nucleation,
      Application to Strain Localization Fields in Al-Cu-Li Aerospace Alloys.
AB  - The displacement discontinuity arising between crack surfaces is assigned to
      smooth densities of crystal defects referred to as disconnections, through the
      incompatibility of the distortion tensor. In a dual way, the disconnections are
      defined as line defects terminating surfaces where the displacement encounters a
      discontinuity. A conservation statement for the crack opening displacement
      provides a framework for disconnection dynamics in the form of transport laws. A
      similar methodology applied to the discontinuity of the plastic displacement due
      to dislocations results in the concurrent involvement of dislocation densities in
      the analysis. Non-linearity of the geometrical setting is assumed for defining
      the elastic distortion incompatibility in the presence of both dislocations and
      disconnections, as well as for their transport. Crack nucleation in the presence
      of thermally-activated fluctuations of the atomic order is shown to derive from
      this nonlinearity in elastic brittle materials, without any algorithmic rule or
      ad hoc material parameter. Digital image correlation techniques applied to the
      analysis of tensile tests on ductile Al-Cu-Li samples further demonstrate the
      ability of the disconnection density concept to capture crack nucleation and
      relate strain localization bands to consistent disconnection fields and to the
      eventual occurrence of complex and combined crack modes in these alloys.

PMID- 29584654
TI  - Concentration and Risk Evaluation of Polycyclic Aromatic Hydrocarbons in Urban
      Soil in the Typical Semi-Arid City of Xi'an in Northwest China.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants,
      presenting potential threats to the ecological environment and human health.
      Sixty-two urban soil samples were collected in the typical semi-arid city of
      Xi'an in Northwest China. They were analyzed for concentration, pollution, and
      ecological and health risk of sixteen U.S. Environmental Protection Agency
      priority PAHs. The total concentrations of the sixteen PAHs (Sigma16PAHs) in the
      urban soil ranged from 390.6 to 10,652.8 ug/kg with an average of 2052.6 ug/kg.
      The concentrations of some individual PAHs in the urban soil exceeded Dutch
      Target Values of Soil Quality and the Sigma16PAHs represented heavy pollution.
      Pyrene and dibenz[a,h]anthracene had high ecological risk to aquatic/soil
      organisms, while other individual PAHs showed low ecological risk. The total
      ecological risk of PAHs to aquatic/soil organisms is classified as moderate.
      Toxic equivalency quantities (TEQs) of the sixteen PAHs varied between 21.16 and
      1625.78 ug/kg, with an average of 423.86 ug/kg, indicating a relatively high
      toxicity potential. Ingestion and dermal adsorption of soil dust were major
      pathways of human exposure to PAHs from urban soil. Incremental lifetime cancer
      risks (ILCRs) of human exposure to PAHs were 2.86 * 10-5 for children and 2.53 *
      10-5 for adults, suggesting that the cancer risk of human exposure to PAHs from
      urban soil is acceptable.

PMID- 29584655
TI  - Performance of Different Immobilized Lipases in the Syntheses of Short- and Long
      Chain Carboxylic Acid Esters by Esterification Reactions in Organic Media.
AB  - Short-chain alkyl esters and sugar esters are widely used in the food,
      pharmaceutical and cosmetic industries due to their flavor and emulsifying
      characteristics, respectively. Both compounds can be synthesized via biocatalysis
      using lipases. This work aims to compare the performance of commercial lipases
      covalently attached to dry acrylic beads functionalized with oxirane groups
      (lipases from Candida antarctica type B-IMMCALB-T2-350, Pseudomonas fluorescens
      IMMAPF-T2-150, and Thermomyces lanuginosus-IMMTLL-T2-150) and a home-made
      biocatalyst (lipase from Pseudomonas fluorescens adsorbed onto silica coated with
      octyl groups, named PFL-octyl-silica) in the syntheses of short- and long-chain
      carboxylic acid esters. Esters with flavor properties were synthetized by
      esterification of acetic and butyl acids with several alcohols (e.g., ethanol, 1
      butanol, 1-hexanol, and isoamyl alcohol), and sugar esters were synthetized by
      esterification of oleic and lauric acids with fructose and lactose. All
      biocatalysts showed similar performance in the syntheses of short-chain alkyl
      esters, with conversions ranging from 88.9 to 98.4%. However, in the syntheses of
      sugar esters the performance of PFL-octyl-silica was almost always lower than the
      commercial IMMCALB-T2-350, whose conversion was up to 96% in the synthesis of
      fructose oleate. Both biocatalysts showed high operational stability in organic
      media, thus having great potential for biotransformations.

PMID- 29584656
TI  - Magnetic Graphene Oxide for Dual Targeted Delivery of Doxorubicin and
      Photothermal Therapy.
AB  - To develop a pH-sensitive dual targeting magnetic nanocarrier for chemo
      phototherapy in cancer treatment, we prepared magnetic graphene oxide (MGO) by
      depositing Fe3O4 magnetic nanoparticles on graphene oxide (GO) through chemical
      co-precipitation. MGO was modified with polyethylene glycol (PEG) and cetuximab
      (CET, an epidermal growth factor receptor (EGFR) monoclonal antibody) to obtain
      MGO-PEG-CET. Since EGFR was highly expressed on the tumor cell surface, MGO-PEG
      CET was used for dual targeted delivery an anticancer drug doxorubicin (DOX). The
      physico-chemical properties of MGO-PEG-CET were fully characterized by dynamic
      light scattering, transmission electron microscopy, X-ray diffraction, Fourier
      transform Infrared spectroscopy, thermogravimetric analysis, and superconducting
      quantum interference device. Drug loading experiments revealed that DOX
      adsorption followed the Langmuir isotherm with a maximal drug loading capacity of
      6.35 mg/mg, while DOX release was pH-dependent with more DOX released at pH 5.5
      than pH 7.4. Using quantum-dots labeled nanocarriers and confocal microscopy,
      intracellular uptakes of MGO-PEG-CET by high EGFR-expressing CT-26 murine
      colorectal cells was confirmed to be more efficient than MGO. This cellular
      uptake could be inhibited by pre-incubation with CET, which confirmed the
      receptor-mediated endocytosis of MGO-PEG-CET. Magnetic targeted killing of CT-26
      was demonstrated in vitro through magnetic guidance of MGO-PEG-CET/DOX, while the
      photothermal effect could be confirmed in vivo and in vitro after exposure of MGO
      PEG-CET to near-infrared (NIR) laser light. In addition, the biocompatibility
      tests indicated MGO-PEG-CET showed no cytotoxicity toward fibroblasts and
      elicited minimum hemolysis. In vitro cytotoxicity tests showed the half maximal
      inhibitory concentration (IC50) value of MGO-PEG-CET/DOX toward CT-26 cells was
      1.48 ug/mL, which was lower than that of MGO-PEG/DOX (2.64 ug/mL). The IC50 value
      could be further reduced to 1.17 ug/mL after combining with photothermal therapy
      by NIR laser light exposure. Using subcutaneously implanted CT-26 cells in BALB/c
      mice, in vivo anti-tumor studies indicated the relative tumor volumes at day 14
      were 12.1 for control (normal saline), 10.1 for DOX, 9.5 for MGO-PEG-CET/DOX, 5.8
      for MGO-PEG-CET/DOX + magnet, and 0.42 for MGO-PEG-CET/DOX + magnet + laser.
      Therefore, the dual targeting MGO-PEG-CET/DOX could be suggested as an effective
      drug delivery system for anticancer therapy, which showed a 29-fold increase in
      therapeutic efficacy compared with control by combining chemotherapy with
      photothermal therapy.

PMID- 29584658
TI  - A Robust Real Time Direction-of-Arrival Estimation Method for Sequential Movement
      Events of Vehicles.
AB  - Parameters estimation of sequential movement events of vehicles is facing the
      challenges of noise interferences and the demands of portable implementation. In
      this paper, we propose a robust direction-of-arrival (DOA) estimation method for
      the sequential movement events of vehicles based on a small Micro-Electro
      Mechanical System (MEMS) microphone array system. Inspired by the incoherent
      signal-subspace method (ISM), the method that is proposed in this work employs
      multiple sub-bands, which are selected from the wideband signals with high
      magnitude-squared coherence to track moving vehicles in the presence of wind
      noise. The field test results demonstrate that the proposed method has a better
      performance in emulating the DOA of a moving vehicle even in the case of severe
      wind interference than the narrowband multiple signal classification (MUSIC)
      method, the sub-band DOA estimation method, and the classical two-sided
      correlation transformation (TCT) method.

PMID- 29584657
TI  - The Neurotoxic Role of Extracellular Tau Protein.
AB  - Tauopathies are a class of neurodegenerative diseases associated with the
      microtubule-associated protein tau, with Alzheimer's disease (AD) being the most
      prevalent related disorder. Neurofibrillary tangles (NFTs) are one of the
      neuropathological hallmarks present in the brains of AD patients. Because NFTs
      are aberrant intracellular inclusions formed by hyperphosphorylated tau, it was
      initially proposed that phosphorylated and/or aggregated intracellular tau
      protein was causative of neuronal death. However, recent studies suggest a toxic
      role for non-phosphorylated and non-aggregated tau when it is located in the
      brain extracellular space. In this work, we will discuss the neurotoxic role of
      extracellular tau as well its involvement in the spreading of tau pathologies.

PMID- 29584659
TI  - Is What Low-Income Brazilians Are Eating in Popular Restaurants Contributing to
      Promote Their Health?
AB  - This study evaluates the healthfulness of the meals offered to and consumed by
      low-income Brazilians in Popular Restaurants (PR). It is a cross-sectional,
      exploratory study. The final sample includes 36 PRs, respecting the
      stratification criteria for each of the five Brazilian regions. To identify the
      quantity and quality of food consumption, consumers' meals are evaluated. The
      sample calculation uses a minimum of 41 consumers in each PR. Consumption
      evaluation is carried out by weighing and direct observation of the meal that
      each consumer served to his plate. Each dish of the meals had its Technical
      preparation files (TPF) developed by observing the production and weighing all
      the ingredients. Evaluations of Energy density (ED), meal's weight components and
      sodium composition are conducted. Plate's composition is compared to "My plate"
      guidelines United States Department of Agriculture (USDA). The final sample
      includes 1771 low-income Brazilians consumers. The plate of PRs consumers is
      adequate only for the "protein group" in comparison to "My plate". Rice and beans
      compose more than 50% of the plate's weight, as expected, since it is a Brazilian
      habit of consumption at lunch. Thus, grains are the major group consumed by PRs
      consumers. The average ED for all PRs is 1.34 kcal/g. Regarding sodium content,
      rice and main courses presented the highest values and are classified as high,
      according to Food and Drug Administration (FDA). Concerning sodium, PRs are
      putting Brazilian low-income population at risk for chronic diseases. However, in
      general, PRs are good choices because they promote access to cheap and quality
      traditional Brazilian foods.

PMID- 29584661
TI  - How Socio-Environmental Factors Are Associated with Japanese Encephalitis in
      Shaanxi, China-A Bayesian Spatial Analysis.
AB  - Evidence indicated that socio-environmental factors were associated with
      occurrence of Japanese encephalitis (JE). This study explored the association of
      climate and socioeconomic factors with JE (2006-2014) in Shaanxi, China. JE data
      at the county level in Shaanxi were supplied by Shaanxi Center for Disease
      Control and Prevention. Population and socioeconomic data were obtained from the
      China Population Census in 2010 and statistical yearbooks. Meteorological data
      were acquired from the China Meteorological Administration. A Bayesian
      conditional autoregressive model was used to examine the association of
      meteorological and socioeconomic factors with JE. A total of 1197 JE cases were
      included in this study. Urbanization rate was inversely associated with JE
      incidence during the whole study period. Meteorological variables were
      significantly associated with JE incidence between 2012 and 2014. The excessive
      precipitation at lag of 1-2 months in the north of Shaanxi in June 2013 had an
      impact on the increase of local JE incidence. The spatial residual variations
      indicated that the whole study area had more stable risk (0.80-1.19 across all
      the counties) between 2012 and 2014 than earlier years. Public health
      interventions need to be implemented to reduce JE incidence, especially in rural
      areas and after extreme weather.

PMID- 29584662
TI  - Development of a beta-Lactoglobulin Sensor Based on SPR for Milk Allergens
      Detection.
AB  - A sensitive and label-free surface plasmon resonance (SPR) based sensor was
      developed in this work for the detection of milk allergens. beta-lactoglobulin
      (BLG) protein was used as the biomarker for cow milk detection. This is to be
      used directly in final rinse samples of cleaning in-place (CIP) systems of food
      manufacturers. The affinity assay was optimised and characterised before a
      standard curve was performed in pure buffer conditions, giving a detection limit
      of 0.164 ug mL-1 as a direct binding assay. The detection limit can be further
      enhanced through the use of a sandwich assay and amplification with
      nanomaterials. However, this was not required here, as the detection limit
      achieved exceeded the required allergen detection levels of 2 ug mL-1 for beta
      lactoglobulin. The binding affinities of the polyclonal antibody for BLG,
      expressed by the dissociation constant (KD), were equal to 2.59 * 10-9 M. The
      developed SPR-based sensor offers several advantages in terms of label-free
      detection, real-time measurements, potential on-line system and superior
      sensitivity when compared to ELISA-based techniques. The method is novel for this
      application and could be applied to wider food allergen risk management
      decision(s) in food manufacturing.

PMID- 29584663
TI  - Comments on: "Transcranial Direct Current Stimulation for Obsessive-Compulsive
      Disorder: A Systematic Review".
AB  - Dear Editor, Brunelin et al. [1] recently conducted a systematic review that
      evaluated the effect of applied transcranial direct current stimulation (tDCS) on
      patients with obsessive compulsive disorder (OCD).[...].

PMID- 29584664
TI  - Comparison of Portable and Bench-Top Spectrometers for Mid-Infrared Diffuse
      Reflectance Measurements of Soils.
AB  - Mid-infrared (MIR) spectroscopy has received widespread interest as a method to
      complement traditional soil analysis. Recently available portable MIR
      spectrometers additionally offer potential for on-site applications, given
      sufficient spectral data quality. We therefore tested the performance of the
      Agilent 4300 Handheld FTIR (DRIFT spectra) in comparison to a Bruker Tensor 27
      bench-top instrument in terms of (i) spectral quality and measurement noise
      quantified by wavelet analysis; (ii) accuracy of partial least squares (PLS)
      calibrations for soil organic carbon (SOC), total nitrogen (N), pH, clay and sand
      content with a repeated cross-validation analysis; and (iii) key spectral regions
      for these soil properties identified with a Monte Carlo spectral variable
      selection approach. Measurements and multivariate calibrations with the handheld
      device were as good as or slightly better than Bruker equipped with a DRIFT
      accessory, but not as accurate as with directional hemispherical reflectance
      (DHR) data collected with an integrating sphere. Variations in noise did not
      markedly affect the accuracy of multivariate PLS calibrations. Identified key
      spectral regions for PLS calibrations provided a good match between Agilent and
      Bruker DHR data, especially for SOC and N. Our findings suggest that portable
      FTIR instruments are a viable alternative for MIR measurements in the laboratory
      and offer great potential for on-site applications.

PMID- 29584665
TI  - Self-Sensing of Position-Related Loads in Continuous Carbon Fibers-Embedded 3D
      Printed Polymer Structures Using Electrical Resistance Measurement.
AB  - Condition monitoring in polymer composites and structures based on continuous
      carbon fibers show overwhelming advantages over other potentially competitive
      sensing technologies in long-gauge measurements due to their great
      electromechanical behavior and excellent reinforcement property. Although carbon
      fibers have been developed as strain- or stress-sensing agents in composite
      structures through electrical resistance measurements, the electromechanical
      behavior under flexural loads in terms of different loading positions still lacks
      adequate research, which is the most common situation in practical applications.
      This study establishes the relationship between the fractional change in
      electrical resistance of carbon fibers and the external loads at different
      loading positions along the fibers' longitudinal direction. An approach for real
      time monitoring of flexural loads at different loading positions was presented
      simultaneously based on this relationship. The effectiveness and feasibility of
      the approach were verified by experiments on carbon fiber-embedded three
      dimensional (3D) printed thermoplastic polymer beam. The error in using the
      provided approach to monitor the external loads at different loading positions
      was less than 1.28%. The study fully taps the potential of continuous carbon
      fibers as long-gauge sensory agents and reinforcement in the 3D-printed polymer
      structures.

PMID- 29584666
TI  - Infrared Hollow Optical Fiber Probe for Localized Carbon Dioxide Measurement in
      Respiratory Tracts.
AB  - A real-time gas monitoring system based on optical absorption spectroscopy is
      proposed for localized carbon dioxide (CO2) measurement in respiratory tracts. In
      this system, a small gas cell is attached to the end of a hollow optical fiber
      that delivers mid-infrared light with small transmission loss. The diameters of
      the fiber and the gas cell are smaller than 1.2 mm so that the probe can be
      inserted into a working channel of common bronchoscopes. The dimensions of the
      gas cell are designed based on absorption spectra of CO2 standard gases in the
      4.2 MUm wavelength region, which are measured using a Fourier-transform infrared
      spectrometer. A miniature gas cell that is comprised of a stainless-steel tube
      with slots for gas inlet and a micro-mirror is fabricated. A compact probing
      system with a quantum cascade laser (QCL) light source is built using a gas cell
      with a hollow optical fiber for monitoring CO2 concentration. Experimental
      results using human breaths show the feasibility of the system for in-situ
      measurement of localized CO2 concentration in human airways.

PMID- 29584660
TI  - The Different Facets of Extracellular Calcium Sensors: Old and New Concepts in
      Calcium-Sensing Receptor Signalling and Pharmacology.
AB  - The current interest of the scientific community for research in the field of
      calcium sensing in general and on the calcium-sensing Receptor (CaR) in
      particular is demonstrated by the still increasing number of papers published on
      this topic. The extracellular calcium-sensing receptor is the best-known G
      protein-coupled receptor (GPCR) able to sense external Ca2+ changes. Widely
      recognized as a fundamental player in systemic Ca2+ homeostasis, the CaR is
      ubiquitously expressed in the human body where it activates multiple signalling
      pathways. In this review, old and new notions regarding the mechanisms by which
      extracellular Ca2+ microdomains are created and the tools available to measure
      them are analyzed. After a survey of the main signalling pathways triggered by
      the CaR, a special attention is reserved for the emerging concepts regarding CaR
      function in the heart, CaR trafficking and pharmacology. Finally, an overview on
      other Ca2+ sensors is provided.

PMID- 29584667
TI  - Computationally Efficient Automatic Coast Mode Target Tracking Based on Occlusion
      Awareness in Infrared Images.
AB  - This paper proposes the automatic coast mode tracking of centroid trackers for
      infrared images to overcome the target occlusion status. The centroid tracking
      method, using only the brightness information of an image, is still widely used
      in infrared imaging tracking systems because it is difficult to extract
      meaningful features from infrared images. However, centroid trackers are likely
      to lose the track because they are highly vulnerable to screened status by the
      clutter or background. Coast mode, one of the tracking modes, maintains the servo
      slew rate with the tracking rate right before the loss of track. The proposed
      automatic coast mode tracking method makes decisions regarding entering coast
      mode by the prediction of target occlusion and tries to re-lock the target and
      resume the tracking after blind time. This algorithm comprises three steps. The
      first step is the prediction process of the occlusion by checking both matters
      which have target-likelihood brightness and which may screen the target despite
      different brightness. The second step is the process making inertial tracking
      commands to the servo. The last step is the process of re-locking a target based
      on the target modeling of histogram ratio. The effectiveness of the proposed
      algorithm is addressed by presenting experimental results based on computer
      simulation with various test imagery sequences compared to published tracking
      algorithms. The proposed algorithm is tested under a real environment with a
      naval electro-optical tracking system (EOTS) and airborne EO/IR system.

PMID- 29584668
TI  - ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the
      Outer Membrane Factor Family for Its Function.
AB  - Vibrio cholerae ATP-binding cassette transporter VcaM (V. cholerae ABC multidrug
      resistance pump) has previously been shown to confer resistance to a variety of
      medically important drugs. In this study, we set to analyse its properties both
      in vitro in detergent-solubilised state and in vivo to differentiate its
      dependency on auxiliary proteins for its function. We report the first detailed
      kinetic parameters of purified VcaM and the rate of phosphate (Pi) production. To
      determine the possible functional dependencies of VcaM on the tripartite efflux
      pumps we then utilized different E. coli strains lacking the principal secondary
      transporter AcrB (Acriflavine resistance protein), as well as cells lacking the
      outer membrane factor (OMF) TolC (Tolerance to colicins). Consistent with the
      ATPase function of VcaM we found it to be susceptible to sodium orthovanadate
      (NaOV), however, we also found a clear dependency of VcaM function on TolC.
      Inhibitors targeting secondary active transporters had no effects on either VcaM
      conferred resistance or Hoechst 33342 accumulation, suggesting that VcaM might be
      capable of engaging with the TolC-channel without periplasmic mediation by
      additional transporters. Our findings are indicative of VcaM being capable of a
      one-step substrate translocation from cytosol to extracellular space utilising
      the TolC-channel, making it the only multidrug ABC-transporter outside of the
      MacB-family with demonstrable TolC-dependency.

PMID- 29584670
TI  - Computational Simulation Studies on the Binding Selectivity of 1-(1H-Benzimidazol
      5-yl)-5-aminopyrazoles in Complexes with FGFR1 and FGFR4.
AB  - Fibroblast growth factor receptor 1 (FGFR1) has become a potential target for the
      treatment of cancer. Designing FGFR1-selective inhibitors remains fundamental to
      the development of anti-cancer drugs because of highly sequential homology among
      FGFR subtypes. In present work, four inhibitors were examined with intermolecular
      interaction patterns with FGFR1 and FGFR4, respectively, for the exploration of
      binding mechanisms by applying a combined approach of computational techniques,
      including flexible docking, binding site analyses, electronic structure
      computations, molecular dynamic simulations, and binding free energy predictions.
      Molecular simulation-predicted binding conformations and pharmacophoric features
      of these molecules in the active pocket of either FGFR1 or FGFR4. MMPB(GB)SA
      calculated binding free energies were accordant with the ordering of their tested
      potency values. Furthermore, in silico mutations of two residues (FGFR1: Tyr563
      and Ser565) were also performed to check their impact on ligand binding by
      applying MD simulations and binding free energy calculations. The present studies
      may provide a structural understanding of the FGFR1-selective mechanism. The
      viewpoints from computational simulations would be valuable guidelines for the
      development of novel FGFR1-selective inhibitors.

PMID- 29584669
TI  - Small Molecule Catalysts with Therapeutic Potential.
AB  - Catalysts are employed in many areas of research and development where they
      combine high efficiency with often astonishing selectivity for their respective
      substrates. In biology, biocatalysts are omnipresent. Enzymes facilitate highly
      controlled, sophisticated cellular processes, such as metabolic conversions,
      sensing and signalling, and are prominent targets in drug development. In
      contrast, the therapeutic use of catalysts per se is still rather limited. Recent
      research has shown that small molecule catalytic agents able to modulate the
      redox state of the target cell bear considerable promise, particularly in the
      context of inflammatory and infectious diseases, stroke, ageing and even cancer.
      Rather than being "active" on their own in a more traditional sense, such agents
      develop their activity by initiating, promoting, enhancing or redirecting
      reactions between biomolecules already present in the cell, and their activity
      therefore depends critically on the predisposition of the target cell itself.
      Redox catalysts, for instance, preferably target cells with a distinct
      sensitivity towards changes in an already disturbed redox balance and/or
      increased levels of reactive oxygen species. Indeed, certain transition metal,
      chalcogen and quinone agents may activate an antioxidant response in normal cells
      whilst at the same time triggering apoptosis in cancer cells with a different pre
      existing "biochemical redox signature" and closer to the internal redox
      threshold. In pharmacy, catalysts therefore stand out as promising lead
      structures, as sensor/effector agents which are highly effective, fairly
      selective, active in catalytic, i.e., often nanomolar concentrations and also
      very flexible in their structural design.

PMID- 29584671
TI  - E-p-Methoxycinnamoyl-alpha-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated
      from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2
      Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes.
AB  - The nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator
      of gene expression during oxidative stress and drug detoxification. Thus,
      identifying Nrf2 activators to protect from possible cell damage is necessary. In
      this study, we investigated whether E-p-methoxycinnamoyl-alpha-l-rhamnopyranosyl
      ester (MCR), a phenylpropanoid isolated from Scrophularia buergeriana, can
      activate Nrf2 signaling in human keratinocytes (HaCaT). First, we determined the
      dose- and time-dependent effects of MCR on the expression and activity of Nrf2.
      The antioxidant response element-luciferase reporter assay and western blot
      analysis results showed that MCR markedly induced Nrf2 activity and its protein
      expression, respectively. Further, MCR increased both the mRNA and protein levels
      of heme-oxygenase-1, one of the Nrf2 target genes, in the cells. Interestingly,
      we found that Nrf2 stability was remarkably enhanced by MCR. Furthermore,
      ubiquitin-dependent proteasomal degradation of Nrf2 was significantly reduced by
      MCR. Thus, MCR might afford skin protection by enhancing Nrf2 stability or by
      blocking its proteasomal degradation.

PMID- 29584672
TI  - Charge-Controlled Synthetic Hyaluronan-Based Cell Matrices.
AB  - The extracellular matrix (ECM) represents a highly charged and hydrated network
      in which different cells in vertebrate tissues are embedded. Hydrogels as minimal
      ECM mimetics with a controlled chemistry offer the opportunity to vary material
      properties by varying the negative network charge. In this paper, a synthetic
      biology model of the ECM based on natural and highly negatively charged
      polyelectrolyte hyaluronic acid (HA) is characterized with specific emphasis on
      its charge-related bioactivity. Therefore, the thiol-Michael addition click
      reaction is used to produce HA hydrogels with defined network structure and
      charge density. The presented hydrogels show enzymatic degradability and cell
      attachment. These properties depend on both covalent and electrostatic
      interactions within the hydrogel network. Furthermore, no unspecific or specific
      attachment of proteins to the presented hydrogels is observed. In addition, these
      fundamental insights into charge-related ECM behavior and the influence of
      electrostatic properties could also lead to innovations in existing biomedical
      products.

PMID- 29584674
TI  - Investigating Effects of Fused-Deposition Modeling (FDM) Processing Parameters on
      Flexural Properties of ULTEM 9085 using Designed Experiment.
AB  - Fused-deposition modeling (FDM), one of the additive manufacturing (AM)
      technologies, is an advanced digital manufacturing technique that produces parts
      by heating, extruding and depositing filaments of thermoplastic polymers. The
      properties of FDM-produced parts apparently depend on the processing parameters.
      These processing parameters have conflicting advantages that need to be
      investigated. This article focuses on an investigation into the effect of these
      parameters on the flexural properties of FDM-produced parts. The investigation is
      carried out on high-performance ULTEM 9085 material, as this material is
      relatively new and has potential application in the aerospace, military and
      automotive industries. Five parameters: air gap, raster width, raster angle,
      contour number, and contour width, with a full factorial design of the
      experiment, are considered for the investigation. From the investigation, it is
      revealed that raster angle and raster width have the greatest effect on the
      flexural properties of the material. The optimal levels of the process parameters
      achieved are: air gap of 0.000 mm, raster width of 0.7814 mm, raster angle of 0
      degrees , contour number of 5, and contour width of 0.7814 mm, leading to a
      flexural strength of 127 MPa, a flexural modulus of 2400 MPa, and 0.081 flexural
      strain.

PMID- 29584673
TI  - Effects of the Combination of Gliotoxin and Adriamycin on the Adriamycin
      Resistant Non-Small-Cell Lung Cancer A549 Cell Line.
AB  - Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and
      the search for effective compounds against resistant cancer is still advancing.
      Marine organisms are a promising natural resource for the discovery and
      development of anticancer agents. In this study, we examined whether gliotoxin
      (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus,
      inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer
      (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell
      viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via
      fluorescence-activated cell sorting analysis, Hoechst staining, annexin
      V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1)
      staining, and western blotting. We found that GTX induced apoptosis in A549/ADR
      cells through the mitochondria-dependent pathway by disrupting mitochondrial
      membrane potential and activating p53, thereby increasing the expression levels
      of p21, p53 upregulated modulator of apoptosis (PUMA), Bax, cleaved poly (ADP
      ribose) polymerase (PARP), and cleaved caspase-9. More importantly, we discovered
      that GTX works in conjunction with ADR to exert combinational effects on A549/ADR
      cells. In conclusion, our results suggest that GTX may have promising effects on
      ADR-resistant NSCLC cells by inducing mitochondria-dependent apoptosis and
      through the combined effects of sequential treatment with ADR.

PMID- 29584675
TI  - Optical Third Harmonic Generation Using Nickel Nanostructure-Covered Microcube
      Structures.
AB  - We investigated the optical third harmonic generation (THG) signal from
      nanostructure-covered microcubes on Ni. We found that the hierarchical structures
      greatly change the third-order optical nonlinearity of the metallic surface.
      While the symmetry and lightning rod (LR) effects on microstructures did not
      significantly influence the THG, the localized surface plasmon (LSP) effect on
      the nanostructures enhanced it. By removing the nanostructures on the
      hierarchical structures, THG intensity could be strongly suppressed. In the
      present paper, we also discuss the mechanism that enhances THG in nano/micro
      structures.

PMID- 29584676
TI  - Phase Transition of Single-Layer Molybdenum Disulfide Nanosheets under Mechanical
      Loading Based on Molecular Dynamics Simulations.
AB  - The single-layer molybdenum disulfide (SLMoS2) nanosheets have been
      experimentally discovered to exist in two different polymorphs, which exhibit
      different electrical properties, metallic or semiconducting. Herein, molecular
      dynamics (MD) simulations of nanoindentation and uniaxial compression were
      conducted to investigate the phase transition of SLMoS2 nanosheets. Typical load
      deflection curves, stress-strain curves, and local atomic structures were
      obtained. The loading force decreases sharply and then increases again at a
      critical deflection under the nanoindentation, which is inferred to the phase
      transition. In addition to the layer thickness, some related bond lengths and
      bond angles were also found to suddenly change as the phase transition occurs. A
      bell-like hollow, so-called residual deformation, was found to form, mainly due
      to the lattice distortion around the waist of the bell. The effect of indenter
      size on the residual hollow was also analyzed. Under the uniaxial compression
      along the armchair direction, a different phase transition, a uniformly
      quadrilateral structure, was observed when the strain is greater than 27.7%. The
      quadrilateral structure was found to be stable and exhibit metallic conductivity
      in view of the first-principle calculation.

PMID- 29584677
TI  - Indentation Behavior and Mechanical Properties of Tungsten/Chromium co-Doped
      Bismuth Titanate Ceramics Sintered at Different Temperatures.
AB  - A sort of tungsten/chromium(W/Cr) co-doped bismuth titanate (BIT) ceramics
      (Bi4Ti2.95W0.05O12.05 + 0.2 wt % Cr2O3, abbreviate to BTWC) are ordinarily
      sintered between 1050 and 1150  degrees C, and the indentation behavior and
      mechanical properties of ceramics sintered at different temperatures have been
      investigated by both nanoindentation and microindentation technology. Firstly,
      more or less Bi2Ti2O7 grains as the second phase were found in BTWC ceramics, and
      the grain size of ceramics increased with increase of sintering temperatures. A
      nanoindentation test for BTWC ceramics reveals that the testing hardness of
      ceramics decreased with increase of sintering temperatures, which could be
      explained by the Hall-Petch equation, and the true hardness could be calculated
      according to the pressure-state-response (PSR) model considering the indentation
      size effect, where the value of hardness depends on the magnitude of load. While,
      under the application of microsized Vickers, the sample sintered at a lower
      temperature (1050  degrees C) gained four linearly propagating cracks, however,
      they were observed to shorten in the sample sintered at a higher temperature
      (1125  degrees C). Moreover, both the crack deflection and the crack branching
      existed in the latter. The hardness and the fracture toughness of BTWC ceramics
      presented a contrary variational tendency with increase of sintering
      temperatures. A high sintering tends to get a lower hardness and a higher
      fracture toughness, which could be attributed to the easier plastic deformation
      and the stronger crack inhibition of coarse grains, respectively, as well as the
      toughening effect coming from the second phase.

PMID- 29584678
TI  - Experimental Investigation of the Effect of Hydrogen on Fracture Toughness of
      2.25Cr-1Mo-0.25V Steel and Welds after Annealing.
AB  - Hydrogen embrittlement (HE) is a critical issue that hinders the reliability of
      hydrogenation reactors. Hence, it is of great significance to investigate the
      effect of hydrogen on fracture toughness of 2.25Cr-1Mo-0.25V steel and weld. In
      this work, the fracture behavior of 2.25Cr-1Mo-0.25V steel and welds was studied
      by three-point bending tests under hydrogen-free and hydrogen-charged conditions.
      The immersion charging method was employed to pre-charge hydrogen inside specimen
      and the fracture toughness of these joints was evaluated quantitatively. The
      microstructure and grain size of the specimens were observed by scanning electron
      microscopy (SEM) and by metallurgical microscopy to investigate the HE
      mechanisms. It was found that fracture toughness for both the base metal (BM) and
      the weld zone (WZ) significantly decreased under hydrogen-charged conditions due
      to the coexistence of the hydrogen-enhanced decohesion (HEDE) and hydrogen
      enhanced localized plasticity (HELP) mechanisms. Moreover, the formation and
      growth of primary voids were observed in the BM, leading to a superior fracture
      toughness. In addition, the BM compared to the WZ shows superior resistance to HE
      because the finer grain size in the BM leads to a larger grain boundary area,
      thus distributing more of the diffusive hydrogen trapped in the grain boundary
      and reducing the hydrogen content.

PMID- 29584679
TI  - An Extended Chemical Plant Environmental Protection Game on Addressing
      Uncertainties of Human Adversaries.
AB  - Chemical production activities in industrial districts pose great threats to the
      surrounding atmospheric environment and human health. Therefore, developing
      appropriate and intelligent pollution controlling strategies for the management
      team to monitor chemical production processes is significantly essential in a
      chemical industrial district. The literature shows that playing a chemical plant
      environmental protection (CPEP) game can force the chemical plants to be more
      compliant with environmental protection authorities and reduce the potential
      risks of hazardous gas dispersion accidents. However, results of the current
      literature strictly rely on several perfect assumptions which rarely hold in real
      world domains, especially when dealing with human adversaries. To address bounded
      rationality and limited observability in human cognition, the CPEP game is
      extended to generate robust schedules of inspection resources for inspection
      agencies. The present paper is innovative on the following contributions: (i) The
      CPEP model is extended by taking observation frequency and observation cost of
      adversaries into account, and thus better reflects the industrial reality; (ii)
      Uncertainties such as attackers with bounded rationality, attackers with limited
      observation and incomplete information (i.e., the attacker's parameters) are
      integrated into the extended CPEP model; (iii) Learning curve theory is employed
      to determine the attacker's observability in the game solver. Results in the case
      study imply that this work improves the decision-making process for environmental
      protection authorities in practical fields by bringing more rewards to the
      inspection agencies and by acquiring more compliance from chemical plants.

PMID- 29584680
TI  - Development and Characterisation of a Human Chronic Skin Wound Cell Line-Towards
      an Alternative for Animal Experimentation.
AB  - Background: Chronic skin wounds are a growing financial burden for healthcare
      providers, causing discomfort/immobility to patients. Whilst animal chronic wound
      models have been developed to allow for mechanistic studies and to develop/test
      potential therapies, such systems are not good representations of the human
      chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs)
      have permitted an insight into the dysfunctional cellular mechanisms that are
      associated with these wounds. However, such cells strains have a limited
      replicative lifespan and therefore a limited reproducibility/usefulness.
      Objectives: To develop/characterise immortalised cell lines of CWF and patient
      matched normal fibroblasts (NFs). Methods and Results: Immortalisation with human
      telomerase resulted in both CWF and NF proliferating well beyond their
      replicative senescence end-point (respective cell strains senesced as normal).
      Gene expression analysis demonstrated that, whilst proliferation-associated genes
      were up-regulated in the cell lines (as would be expected), the immortalisation
      process did not significantly affect the disease-specific genotype. Immortalised
      CWF (as compared to NF) also retained a distinct impairment in their wound
      repopulation potential (in line with CWF cell strains). Conclusions: These novel
      CWF cell lines are a credible animal alternative and could be a valuable research
      tool for understanding both the aetiology of chronic skin wounds and for
      therapeutic pre-screening.

PMID- 29584681
TI  - Evaluating Community Partnerships Addressing Community Resilience in Los Angeles,
      California.
AB  - Community resilience has grown in importance in national disaster response and
      recovery efforts. However, measurement of community resilience, particularly the
      content and quality of relationships aimed at improving resilience, is lacking.
      To address this gap, we used a social network survey to measure the number, type,
      and quality of relationships among organizations participating in 16 coalitions
      brought together to address community resilience in the Los Angeles Community
      Disaster Resilience project. These coalitions were randomized to one of two
      approaches (community resilience or preparedness). Resilience coalitions received
      training and support to develop these partnerships and implement new activities.
      Both coalition types received expert facilitation by a public health nurse or
      community educator. We also measured the activities each coalition engaged in and
      the extent to which partners participated in these activities at two time points.
      We found that the community resilience coalitions were initially larger and had
      lower trust among members than the preparedness communities. Over time, these
      trust differences dissipated. While both coalitions grew, the resilience
      community coalitions maintained their size difference throughout the project. We
      also found differences in the types of activities implemented by the resilience
      communities; these differences were directly related to the trainings provided.
      This information is useful to organizations seeking guidance on expanding the
      network of community-based organizations that participate in community resilience
      activities.

PMID- 29584682
TI  - Fabrication of Amine-Modified Magnetite-Electrochemically Reduced Graphene Oxide
      Nanocomposite Modified Glassy Carbon Electrode for Sensitive Dopamine
      Determination.
AB  - Amine-modified magnetite (NH2-Fe3O4)/reduced graphene oxide nanocomposite
      modified glassy carbon electrodes (NH2-Fe3O4/RGO/GCEs) were developed for the
      sensitive detection of dopamine (DA). The NH2-Fe3O4/RGO/GCEs were fabricated
      using a drop-casting method followed by an electrochemical reduction process. The
      surface morphologies, microstructure and chemical compositions of the NH2-Fe3O4
      nanoparticles (NPs), reduced graphene oxide (RGO) sheets and NH2-Fe3O4/RGO
      nanocomposites were characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), X-Ray diffraction (XRD) and Fourier
      transform infrared (FTIR) spectroscopy. The electrochemical behaviors of DA on
      the bare and modified GCEs were investigated in phosphate buffer solution (PBS)
      by cyclic voltammetry (CV). Compared with bare electrode and RGO/GCE, the
      oxidation peak current (ipa) on the NH2-Fe3O4/RGO/GCE increase significantly,
      owing to the synergistic effect between NH2-Fe3O4 NPs and RGO sheets. The
      oxidation peak currents (ipa) increase linearly with the concentrations of DA in
      the range of 1 * 10-8 mol/L - 1 * 10-7 mol/L, 1 * 10-7 mol/L - 1 * 10-6 mol/L and
      1 * 10-6 mol/L - 1 * 10-5 mol/L. The detection limit is (4.0 +/- 0.36) *10-9
      mol/L (S/N = 3). Moreover, the response peak currents of DA were hardly
      interfered with the coexistence of ascorbic acid (AA) and uric acid (UA). The
      proposed NH2-Fe3O4/RGO/GCE is successfully applied to the detection of dopamine
      hydrochloride injections with satisfactory results. Together with low cost,
      facile operation, good selectivity and high sensitivity, the NH2-Fe3O4/RGO/GCEs
      have tremendous prospects for the detection of DA in various real samples.

PMID- 29584683
TI  - Mechanical and Thermal Properties of Dental Composites Cured with CAD/CAM
      Assisted Solid-State Laser.
AB  - Over the last three decades, it has been frequently reported that the properties
      of dental restorative composites cured with argon laser are similar or superior
      to those achieved with conventional halogen and light emitting diode (LED) curing
      units. Whereas laser curing is not dependent on the distance between the curing
      unit and the material, such distance represents a drawback for conventional
      curing units. However, a widespread clinical application of this kind of laser
      remains difficult due to cost, heavy weight, and bulky size. Recently, with
      regard to the radiation in the blue region of the spectrum, powerful solid-state
      lasers have been commercialized. In the current research, CAD (computer-aided
      design)/CAM (computer-aided manufacturing) assisted solid-state lasers were
      employed for curing of different dental restorative composites consisting of
      micro- and nanoparticle-reinforced materials based on acrylic resins. Commercial
      LED curing units were used as a control. Temperature rise during the
      photopolymerisation process and bending properties were measured. By providing
      similar light energy dose, no significant difference in temperature rise was
      observed when the two light sources provided similar intensity. In addition,
      after 7 days since curing, bending properties of composites cured with laser and
      LED were similar. The results suggested that this kind of laser would be suitable
      for curing dental composites, and the curing process does not suffer from the tip
      to-tooth distance.

PMID- 29584684
TI  - A New Lignanamide from the Root of Lycium yunnanense Kuang and Its Antioxidant
      Activity.
AB  - A new lignanamide (1), lyciumamide K, together with four known analogues (2-5),
      was isolated from the root of Lycium yunnanense Kuang. Based on HR-ESI-MS, NMR
      spectral data and quantum chemistry ECD calculations, the structure of this new
      compound was confirmed, including its absolute configuration. Evaluation of the
      antioxidant activity of compounds 1-5 in the oxygen radical absorption capacity
      (ORAC) assay showed that they all exhibited significant antioxidant activities.
      Particularly, compound 1 showed the best activity with ORAC values (U/mol) of
      7.90 +/- 0.52. Thus, the new lignanamide may be a good source of bioavtive and
      protective compounds.

PMID- 29584686
TI  - In-Cabin Air Quality during Driving and Engine Idling in Air-Conditioned Private
      Vehicles in Hong Kong.
AB  - Many people spend lengthy periods each day in enclosed vehicles in Hong Kong.
      However, comparably limited data is available about in-cabin air quality in air
      conditioned private vehicles, and the car usage that may affect the air quality.
      Fifty-one vehicles were tested for particulate matter (PM0.3 and PM2.5), total
      volatile organic compounds (TVOCs), carbon monoxide (CO), carbon dioxide (CO2),
      airborne bacteria, and fungi levels during their routine travel journey. Ten of
      these vehicles were further examined for PM0.3, PM2.5, TVOCs, CO, and CO2 during
      engine idling. In general, during driving PM2.5 levels in-cabin reduced overtime,
      but not PM0.3. For TVOCs, 24% vehicles exceeded the recommended Indoor Air
      Quality (IAQ) level in offices and public places set by the Hong Kong
      Environmental Protection Department. The total volatile organic compounds (TVOC)
      concentration positively correlated with the age of the vehicle. Carbon monoxide
      (CO) levels in all of the vehicles were lower than the IAQ recommendation, while
      96% vehicles exceeded the recommended CO2 level of 1000 ppmv; 16% vehicles >5000
      ppmv. Microbial counts were relatively low. TVOCs levels at idle engine were
      higher than that during driving. Although the time we spend in vehicles is short,
      the potential exposure to high levels of pollutants should not be overlooked.

PMID- 29584685
TI  - Characterization of Human Type C Enterotoxin Produced by Clinical S. epidermidis
      Isolates.
AB  - Staphylococcal Enterotoxins (SEs) are superantigens (SAg) originally produced by
      S. aureus, but their presence in coagulase negative staphylococci (CNS) has long
      been suspected. This study aims to better characterize a novel C-like enterotoxin
      expressed by clinical S. epidermidis strains, called SECepi. We isolated and
      characterized SECepi for its molecular and functional properties. The toxin was
      structurally modeled according to its significant similarity with S. aureus SEC3.
      Most of SEC amino acid residues important for the formation of the trimolecular
      Major Histocompatibility Complex II MHCII-SEC-T Cell Receptor TCR complex are
      conserved in SECepi. The functional properties of SECepi were estimated after
      cloning, expression in E. coli, and purification. The recombinant SECepi toxin
      exhibits biological characteristics of a SAg including stimulation of human T
      cell mitogenicity, inducing and releasing high cytokines levels: IL-2, -4, -6, 
      8, -10, IFN-gamma, TNF-alpha and GM-CSF at a dose as low as 3.7 pM. Compared to
      SECaureus, the production of pro-sepsis cytokine IL-6 is significantly higher
      with SECepi-activated lymphocytes. Furthermore, SECepi is stable to heat, pepsin
      or trypsin hydrolysis. The SECepi superantigen produced by CNS is functionally
      very close to that of S. aureus, possibly inducing a systemic inflammatory
      response at least comparable to that of SECaureus, and may account for S.
      epidermidis pathogenicity.

PMID- 29584687
TI  - Association between Resistin Gene Polymorphisms and Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder.
      It is characterized by an inappropriate skin barrier function, allergen
      sensitization, and recurrent skin infections. Resistin is an adipokine expressed
      mainly in macrophages and monocytes; it has a role in the inflammatory process
      and is associated with multiple inflammatory human diseases; however, only few
      studies linked resistin to atopic dermatitis. This study tested the association
      between G>A (rs3745367) and C>T (rs3219177) single nucleotide polymorphisms
      (SNPs) of the RETN gene with atopic dermatitis. In addition, it explored the
      relationship between serum resistin protein and atopic dermatitis. To achieve
      objectives of this study, 162 atopic dermatitis patients and 161 healthy
      participants were recruited in the study. A significant association was detected
      between rs3745367 and atopic dermatitis with age and gender specificity (p <
      0.05), while no significant association between rs3219177 and atopic dermatitis
      was found (p > 0.05). For the serum resistin levels, a significant decrease was
      indicated in atopic dermatitis patients compared to healthy subjects (p < 0.05).
      In conclusion, rs3745367 may play a gender and age-specific role in atopic
      dermatitis. In addition, the significant decrease in the resistin protein level
      confirmed this association.

PMID- 29584688
TI  - Regulated Mesenchymal Stem Cells Mediated Colon Cancer Therapy Assessed by
      Reporter Gene Based Optical Imaging.
AB  - Colorectal cancer is the most common cancer in both men and women and the second
      most common cause of cancer-related deaths. Suicide gene-based therapy with
      suicide gene-transduced mesenchymal stem cells (MSCs) is a promising therapeutic
      strategy. A tetracycline-controlled Tet-On inducible system used to regulate gene
      expression may be a useful tool for gene-based therapies. The aim of this study
      was to develop therapeutic MSCs with a suicide gene that is induced by an
      artificial stimulus, to validate therapeutic gene expression, and to monitor the
      MSC therapy for colon cancer using optical molecular imaging. For our study, we
      designed the Tet-On system using a retroviral vector and developed a response
      plasmid RetroX-TRE (tetracycline response element) expressing a mutant form of
      herpes simplex virus thymidine kinase (HSV1-sr39TK) with dual reporters (eGFP
      Fluc2). Bone marrow-derived MSCs were transduced using a RetroX-Tet3G (Clontech,
      CA, USA) regulatory plasmid and RetroX-TRE-HSV1-sr39TK-eGFP-IRES-Fluc2, for a
      system with a Tet-On (MSC-Tet-TK/Fluc2 or MSC-Tet-TK) or without a Tet-On (MSC
      TK/Fluc2 or MSC-TK) function. Suicide gene engineered MSCs were co-cultured with
      colon cancer cells (CT26/Rluc) in the presence of the prodrug ganciclovir (GCV)
      after stimulation with or without doxycycline (DOX). Treatment efficiency was
      monitored by assessing Rluc (CT26/Rluc) and Fluc (MSC-Tet-TK and MSC-TK) activity
      using optical imaging. The bystander effect of therapeutic MSCs was confirmed in
      CT26/Rluc cells after GCV treatment. Rluc activity in CT26/Rluc cells decreased
      significantly with GCV treatment of DOX(+) cells (p < 0.05 and 0.01) whereas no
      significant changes were observed in DOX(-) cells. In addition, Fluc activity in
      also decreased significantly with DOX(+) MSC-Tet-TK cells, but no signal was
      observed in DOX(-) cells. In addition, an MSC-TK bystander effect was also
      confirmed. We assessed therapy with this system in a colon cancer xenograft model
      (CT26/Rluc). We successfully transduced cells and developed a Tet-On system with
      the suicide gene HSV1-sr39TK. Our results confirmed the therapeutic efficiency of
      a suicide gene with the Tet-On system for colon cancer. In addition, our results
      provide an innovative therapeutic approach using the Tet-On system to eradicate
      tumors by administration of MSC-Tet-TK cells with DOX and GCV.

PMID- 29584690
TI  - Lactic Acid Bacteria from Kefir Increase Cytotoxicity of Natural Killer Cells to
      Tumor Cells.
AB  - The Japanese fermented beverage, homemade kefir, contains six lactic acid
      bacteria: Lactococcus. lactis subsp. Lactis, Lactococcus. lactis subsp. Cremoris,
      Lactococcus. Lactis subsp. Lactis biovar diacetylactis, Lactobacillus plantarum,
      Leuconostoc meseuteroides subsp. Cremoris and Lactobacillus casei. In this study,
      we found that a mixture of the six lactic acid bacteria from kefir increased the
      cytotoxicity of human natural killer KHYG-1 cells to human chronic myelogenous
      leukemia K562 cells and colorectal tumor HCT116 cells. Furthermore, levels of
      mRNA expression and secretion of IFN-gamma (interferon gamma) increased in KHYG-1
      cells that had been treated with the six lactic acid bacteria mixture from kefir.
      The results suggest that the six lactic acid bacteria mixture from kefir has
      strong effects on natural immunity and tumor cell cytotoxicity.

PMID- 29584691
TI  - Synthesis, Self-Assembly, and Drug-Release Properties of New Amphipathic Liquid
      Crystal Polycarbonates.
AB  - New amphiphilic liquid crystal (LC) polycarbonate block copolymers containing
      side-chain cholesteryl units were synthesized. Their structure, thermal
      stability, and LC phase behavior were characterized with Fourier transform
      infrared (FT-IR) spectrum, 1H NMR, gel permeation chromatographic (GPC),
      thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),
      polarizing optical microscope (POM), and XRD methods. The results demonstrated
      that the LC copolymers showed a double molecular arrangement of a smectic A phase
      at room temperature. With the elevating of LC unit content in such LC copolymers,
      the corresponding properties including decomposition temperature (Td), glass
      temperature (Tg), and isotropic temperature (Ti) increased. The LC copolymers
      showed pH-responsive self-assembly behavior under the weakly acidic condition,
      and with more side-chain LC units, the self-assembly process was faster, and the
      formed particle size was smaller. It indicated that the self-assembly driving
      force was derived from the orientational ability of LC. The particle size and
      morphologies of self-assembled microspheres loaded with doxorubicin (DOX),
      together with drug release tracking, were evaluated by dynamic light scattering
      (DLS), SEM, and UV-vis spectroscopy. The results showed that DOX could be quickly
      released in a weakly acidic environment due to the pH response of the self
      assembled microspheres. This would offer a new strategy for drug delivery in
      clinic applications.

PMID- 29584689
TI  - Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.
AB  - Epidermal stem cells reside within the specific anatomic location, called niche,
      which is a microenvironment that interacts with stem cells to regulate their
      fate. Regulation of many important processes, including maintenance of stem cell
      quiescence, self-renewal, and homeostasis, as well as the regulation of division
      and differentiation, are common functions of the stem cell niche. As it was shown
      in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell
      niches in various tissues, including that of skin. In epidermis, ECM is
      represented, primarily, by a highly specialized ECM structure, basement membrane
      (BM), which separates the epidermal and dermal compartments. Epidermal stem cells
      contact with BM, but when they lose the contact and migrate to the overlying
      layers, they undergo terminal differentiation. When considering all of these
      factors, ECM is of fundamental importance in regulating epidermal stem cells
      maintenance, proper mobilization, and differentiation. Here, we summarize the
      remarkable progress that has recently been made in the research of ECM role in
      regulating epidermal stem cell fate, paying special attention to the hair
      follicle stem cell niche. We show that the destruction of ECM components impairs
      epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM
      molecular structure as well as the development of in vitro system for stem cell
      maintaining by ECM proteins may bring us to developing new approaches for
      regenerative medicine.

PMID- 29584692
TI  - Tribological Behavior and the Mild-Severe Wear Transition of Mg97Zn1Y2 Alloy with
      a LPSO Structure Phase.
AB  - Dry friction and wear tests were performed on as-cast Mg97Zn1Y2 alloy using a pin
      on-disc configuration. Coefficients of friction and wear rates were measured as a
      function of applied load at sliding speeds of 0.2, 0.8 and 3.0 m/s. The wear
      mechanisms were identified in the mild and severe wear regimes by means of
      morphological observation and composition analysis of worn surfaces using
      scanning electron microscope (SEM) and energy dispersive X-ray spectrometer
      (EDS). Analyses of microstructure and hardness changes in subsurfaces verified
      the microstructure transformation from the deformed to the dynamically
      recrystallized, and properties changed from the strain hardening to dynamic
      crystallization (DRX) softening before and after the mild-severe wear transition.
      The mild-severe wear transition can be determined by a proposed contact surface
      DRX temperature criterion, from which the critical DRX temperatures at different
      sliding speeds are calculated using DRX dynamics; hence transition loads can also
      be calculated using a transition load model. The calculated transition loads are
      in good agreement with the measured ones, demonstrating the validity and
      applicability of the contact surface DRX temperature criterion.

PMID- 29584694
TI  - Subsurface Damage in Polishing Process of Silicon Carbide Ceramic.
AB  - Subsurface damage (SSD) in the polishing process of silicon carbide (SiC) ceramic
      presents one of the most significant challenges for practical applications. In
      this study, the theoretical models of SSD depth are established on the basis of
      the material removal mechanism and indentation fracture mechanics in the SiC
      ceramic polishing process. In addition, the three-dimensional (3D) models of
      single grit polishing are also developed by using the finite element simulation;
      thereby, the dynamic effects of different process parameters on SSD depth are
      analyzed. The results demonstrate that the material removal was mainly in brittle
      mode when the cutting depth was larger than the critical depth of the brittle
      material. The SSD depth increased as the polishing depth and abrasive grain size
      increased, and decreased with respect to the increase in polishing speed. The
      experimental results suggested a good agreement with the theoretical simulation
      results in terms of SSD depth as a function of polishing depth, spindle speed,
      and abrasive grain size. This study provides a mechanistic insight into the
      dependence of SSD on key operational parameters in the polishing process of SiC
      ceramic.

PMID- 29584695
TI  - A Time-Variant Reliability Model for Copper Bending Pipe under Seawater-Active
      Corrosion Based on the Stochastic Degradation Process.
AB  - In the degradation process, the randomness and multiplicity of variables are
      difficult to describe by mathematical models. However, they are common in
      engineering and cannot be neglected, so it is necessary to study this issue in
      depth. In this paper, the copper bending pipe in seawater piping systems is taken
      as the analysis object, and the time-variant reliability is calculated by solving
      the interference of limit strength and maximum stress. We did degradation
      experiments and tensile experiments on copper material, and obtained the limit
      strength at each time. In addition, degradation experiments on copper bending
      pipe were done and the thickness at each time has been obtained, then the
      response of maximum stress was calculated by simulation. Further, with the help
      of one kind of Monte Carlo method we propose, the time-variant reliability of
      copper bending pipe was calculated based on the stochastic degradation process
      and interference theory. Compared with traditional methods and verified by
      maintenance records, the results show that the time-variant reliability model
      based on the stochastic degradation process proposed in this paper has better
      applicability in the reliability analysis, and it can be more convenient and
      accurate to predict the replacement cycle of copper bending pipe under seawater
      active corrosion.

PMID- 29584693
TI  - Is Matrix Gla Protein Associated with Vascular Calcification? A Systematic
      Review.
AB  - Specific patient cohorts are at increased risk of vascular calcification.
      Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent
      protein, is reported to be an important inhibitor of vascular calcification and
      may have clinical potential to modify the progression of vascular calcification
      through regulation of functional MGP fractions. This systematic review examines
      twenty-eight studies which assess the relationship between circulating protein
      expressions of MGP species and vascular calcification in different arterial beds.
      The included studies examined participants with atherosclerosis, chronic kidney
      disease (CKD), diabetes, healthy participants, vitamin K supplementation,
      measured plasma vitamin K levels and vitamin K antagonist usage. The current
      review reports conflicting results regarding MGP fractions with respect to local
      calcification development indicating that a multifaceted relationship exists
      between the MGP and calcification. A primary concern regarding the studies in
      this review is the large degree of variability in the calcification location
      assessed and the fraction of MGP measured. This review suggests that different
      underlying molecular mechanisms can accelerate local disease progression within
      the vasculature, and specific circulating fractions of MGP may be influenced
      differently depending on the local disease states related to vascular
      calcification development. Further studies examining the influence of non
      functional MGP levels, with respect to specific calcified arterial beds, are
      warranted.

PMID- 29584696
TI  - beta4 and beta6 Integrin Expression Is Associated with the Subclassification and
      Clinicopathological Features of Intrahepatic Cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous group of cancers of the
      intrahepatic biliary tract. However, few studies have evaluated integrin
      expression according to an ICC subgroup. We immunohistochemically investigated
      alpha6beta4 (beta4) and alphavbeta6 (beta6) integrin expressions in 48 ICCs, and
      evaluated their relationship with clinical and pathological parameters and ligand
      expression, as well as transforming growth factor (TGF)-beta1. beta4 and beta6
      expressions were detected in 46 (96%) and 35 (73%) ICC cases, respectively. We
      classified ICC into negative, low (beta4, 29 cases; beta6, 36 cases), or high
      (beta4, 19 cases; beta6, 12 cases) integrin expression groups. beta4 and beta6
      integrin levels were higher in the non-peripheral central localization type ICC
      than in the peripheral localization type; they were also higher in the periductal
      infiltrating or intraductal-growth types than in the mass-forming type ICC;
      lastly, they were higher in the well-differentiated type than in the poorly
      differentiated type ICC. High expression was related to bile duct invasion. In
      addition, beta4 and beta6 expressions were associated with mucin production and
      the expression of cytoplasmic epithelial membrane antigen, laminin-5, and
      tenascin-C. TGF-beta1 was correlated with beta6 expression and poor overall
      survival. These results suggest that integrin expression is associated with
      subclassification and clinicopathological features of ICC through the coincident
      expression of their ligands and TGF-beta1.

PMID- 29584697
TI  - Karyotype Evolution in Birds: From Conventional Staining to Chromosome Painting.
AB  - In the last few decades, there have been great efforts to reconstruct the
      phylogeny of Neoaves based mainly on DNA sequencing. Despite the importance of
      karyotype data in phylogenetic studies, especially with the advent of
      fluorescence in situ hybridization (FISH) techniques using different types of
      probes, the use of chromosomal data to clarify phylogenetic proposals is still
      minimal. Additionally, comparative chromosome painting in birds is restricted to
      a few orders, while in mammals, for example, virtually all orders have already
      been analyzed using this method. Most reports are based on comparisons using
      Gallus gallus probes, and only a small number of species have been analyzed with
      more informative sets of probes, such as those from Leucopternis albicollis and
      Gyps fulvus, which show ancestral macrochromosomes rearranged in alternative
      patterns. Despite this, it is appropriate to review the available cytogenetic
      information and possible phylogenetic conclusions. In this report, the authors
      gather both classical and molecular cytogenetic data and describe some
      interesting and unique characteristics of karyotype evolution in birds.

PMID- 29584699
TI  - Feasibility of Using Elastic Wave Velocity Monitoring for Early Warning of
      Rainfall-Induced Slope Failure.
AB  - Rainfall-induced landslides are one of the most widespread slope instability
      phenomena posing a serious risk to public safety worldwide so that their temporal
      prediction is of great interest to establish effective warning systems. The
      objective of this study is to determine the effectiveness of elastic wave
      velocities in the surface layer of the slope in monitoring, prediction and early
      warning of landslide. The small-scale fixed and varied, and large-scale slope
      model tests were conducted. Analysis of the results has established that the
      elastic wave velocity continuously decreases in response of moisture content and
      deformation and there was a distinct surge in the decrease rate of wave velocity
      when failure was initiated. Based on the preliminary results of this analysis,
      the method using the change in elastic wave velocity proves superior for
      landslide early warning and suggests that a warning be issued at switch of wave
      velocity decrease rate.

PMID- 29584698
TI  - Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of
      Thyroid Carcinomas Induced by the RET/PTC1 Oncogene.
AB  - POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging
      cancer-related gene that is downregulated in different human malignancies,
      including thyroid cancer, where its levels gradually decrease going from
      papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated
      highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1
      expression in thyroid cancer cells reverted their malignant phenotype by inducing
      mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for
      PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we
      investigated the consequences of the homozygous and heterozygous loss of PATZ1 in
      the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1
      oncogene under the thyroid specific control of the thyroglobulin promoter
      RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed
      with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced
      thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of
      the Patz1 gene. However, both RET/PTC1TG;Patz1+/- and RET/PTC1TG;Patz1-/- mice
      developed a more aggressive thyroid cancer phenotype-characterized by higher Ki
      67 expression, presence of ATCs, and increased incidence of solid variants of PTC
      than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that
      PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that
      it cooperates with RET/PTC1 in thyroid cancer progression.

PMID- 29584700
TI  - Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm
      Magnetoliposomes?
AB  - Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release
      from magnetoliposomes through a magneto-nanomechanical approach, where the
      mechanical actuation of the MNPs is used to enhance the membrane permeability.
      This result can be effectively achieved with low intensity non-thermal
      alternating magnetic field (AMF), which, however, found rare clinic application.
      Therefore, a different modality of generating non-thermal magnetic fields has now
      been investigated. Specifically, the ability of the intermittent signals
      generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to
      verify if, once applied to high-transition temperature magnetoliposomes (high-Tm
      MLs), they could be able to efficiently trigger the release of a hydrophilic
      model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean
      phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye
      was evaluated under the effect of PEMFs for different times. The MNPs motions
      produced by PEMF could effectively increase the bilayer permeability, without
      affecting the liposomes integrity and resulted in nearly 20% of release after 3 h
      exposure. Therefore, the current contribution provides an exciting proof-of
      concept for the ability of PEMFS to trigger drug release, considering that PEMFS
      find already application in therapy due to their anti-inflammatory effects.

PMID- 29584701
TI  - Optimizing Propagation of Staphylococcus aureus Infecting Bacteriophage vB_SauM
      phiIPLA-RODI on Staphylococcus xylosus Using Response Surface Methodology.
AB  - The use of bacteriophages for killing pathogenic bacteria is a feasible
      alternative to antibiotics and disinfectants. To obtain the large quantities of
      phages required for this application, large-scale production of bacteriophages
      must be optimized. This study aims to define conditions that maximize the phage
      yield of the virulent and polyvalent staphylococcal bacteriophage vB_SauM-phiIPLA
      RODI in broth culture, using the food-grade species Staphylococcus xylosus as the
      host strain to reduce the risk of growing massive quantities of pathogenic
      bacteria and therefore, to ensure the safety of the final phage stock. The effect
      of four variables, namely initial bacterial concentration (5.66-8.40 log10 colony
      forming unit (CFU)/mL), initial phage concentration (5-8 log10 plaque-forming
      unit (PFU)/mL), temperature (21-40  degrees C) and agitation (20-250 rpm), on
      phage yield (response) was studied by using response surface methodology (RSM).
      Successive experimental designs showed that agitation did not significantly
      impact phage yield, while temperature did have a significant effect, with 38 
      degrees C being the optimum for phage propagation. The results allowed the design
      of a model to describe phage yield as a function of the initial bacterial and
      phage concentrations at fixed agitation (135 rpm), and optimum temperature (38 
      degrees C). The maximum experimental phage yield obtained was 9.3 log10 PFU/mL,
      while that predicted by the model under the optimized conditions (7.07 log10
      CFU/mL initial bacterial population and 6.00 log10 PFU/mL initial phage titer)
      was 9.25 +/- 0.30 log10 PFU/mL, with the desirability of 0.96. This yield is
      comparable to that obtained when the phage was propagated on the original host,
      Staphylococcus aureus. Bacteriophage phiIPLA-RODI showed the same host range and
      very similar biofilm removal ability regardless of the staphylococcal species
      used for its propagation. The results presented in this study show the
      suitability of using a food-grade strain of S. xylosus for the propagation of S.
      aureus infecting phages and the application of RSM to define the optimal
      propagation conditions.

PMID- 29584703
TI  - ABS-SmartComAgri: An Agent-Based Simulator of Smart Communication Protocols in
      Wireless Sensor Networks for Debugging in Precision Agriculture.
AB  - Smart communication protocols are becoming a key mechanism for improving
      communication performance in networks such as wireless sensor networks. However,
      the literature lacks mechanisms for simulating smart communication protocols in
      precision agriculture for decreasing production costs. In this context, the
      current work presents an agent-based simulator of smart communication protocols
      for efficiently managing pesticides. The simulator considers the needs of
      electric power, crop health, percentage of alive bugs and pesticide consumption.
      The current approach is illustrated with three different communication protocols
      respectively called (a) broadcast, (b) neighbor and (c) low-cost neighbor. The
      low-cost neighbor protocol obtained a statistically-significant reduction in the
      need of electric power over the neighbor protocol, with a very large difference
      according to the common interpretations about the Cohen's d effect size. The
      presented simulator is called ABS-SmartComAgri and is freely distributed as open
      source from a public research data repository. It ensures the reproducibility of
      experiments and allows other researchers to extend the current approach.

PMID- 29584702
TI  - Role of Macrophages in Brain Tumor Growth and Progression.
AB  - The role of macrophages in the growth and the progression of tumors has been
      extensively studied in recent years. A large body of data demonstrates that
      macrophage polarization plays an essential role in the growth and progression of
      brain tumors, such as gliomas, meningiomas, and medulloblastomas. The brain
      neoplasm cells have the ability to influence the polarization state of the tumor
      associated macrophages. In turn, innate immunity cells have a decisive role
      through regulation of the acquired immune response, but also through humoral
      cross-talking with cancer cells in the tumor microenvironment. Neoangiogenesis,
      which is an essential element in glial tumor progression, is even regulated by
      the tumor associated macrophages, whose activity is linked to other factors, such
      as hypoxia. In addition, macrophages play a decisive role in establishing the
      entry into the bloodstream of cancer cells. As is well known, the latter
      phenomenon is also present in brain tumors, even if they only rarely metastasize.
      Looking ahead in the future, we can imagine that characterizing the relationships
      between tumor and tumor associated macrophage, as well as the study of
      circulating tumor cells, could give us useful tools in prognostic evaluation and
      therapy. More generally, the study of innate immunity in brain tumors can boost
      the development of new forms of immunotherapy.

PMID- 29584704
TI  - Roles of Mitochondrial DNA Mutations in Stem Cell Ageing.
AB  - Mitochondrial DNA (mtDNA) mutations accumulate in somatic stem cells during
      ageing and cause mitochondrial dysfunction. In this review, we summarize the
      studies that link mtDNA mutations to stem cell ageing. We discuss the age-related
      behaviours of the somatic mtDNA mutations in stem cell populations and how they
      potentially contribute to stem cell ageing by altering mitochondrial properties
      in humans and in mtDNA-mutator mice. We also draw attention to the diverse fates
      of the mtDNA mutations with different origins during ageing, with potential
      selective pressures on the germline inherited but not the somatic mtDNA
      mutations.

PMID- 29584705
TI  - Particulate Guanylyl Cyclase A/cGMP Signaling Pathway in the Kidney: Physiologic
      and Therapeutic Indications.
AB  - The particulate guanylyl cyclase A (pGC-A)/cGMP pathway plays important roles in
      regulating renal physiological function and as well as in counteracting
      pathophysiological conditions. Naturally occurring peptide pGC-A activators
      consist of atrial natriuretic peptide (ANP), b-type NP (BNP), and urodilatin
      (URO). These activators bind and activate pGC-A, generating the second messenger
      cyclic 3',5' guanosine monophosphate (cGMP). Cyclic GMP binds to downstream
      pathway effector molecules including protein kinase G (PKG), cGMP-gated ion
      channels, and phosphodiesterases (PDEs). These mediators result in a variety of
      physiological actions in the kidney, including diuresis, natriuresis, increased
      glomerular filtration rate (GFR) and organ protection, thus, opposing renal
      cellular injury and remodeling. Downstream proteins regulated by PKG include
      collagen 1 (Col-1), transforming growth factor beta (TGF-beta) and apoptosis
      related proteins. In addition to their physiological regulatory effects, pGC
      A/cGMP signaling is critical for preserving renal homeostasis in different renal
      diseases such as acute kidney injury (AKI). Regarding therapeutic options, native
      pGC-A activators have short half-lives and their activity can be further enhanced
      by advances in innovative peptide engineering. Thus, novel designer peptide pGC-A
      activators with enhanced renal activity are under development.

PMID- 29584706
TI  - Tri-Trophic Impacts of Bt-Transgenic Maize on Parasitoid Size and Fluctuating
      Asymmetry in Native vs. Novel Host-Parasitoid Interactions in East Africa.
AB  - Environmental stress can affect trait size and cause an increase in the
      fluctuating asymmetry (FA) of bilateral morphological traits in many animals. For
      insect parasitoids, feeding of hosts on transgenic maize, expressing a Bacillus
      thuringiensis toxin gene is a potential environmental stressor. We compared the
      size of antennae, forewings, and tibia, as well as their FA values, in two
      parasitoids developed on two East African host species feeding on non-transgenic
      vs. transgenic maize. The two lepidopteran stem-borer hosts were the native
      Sesamia calamistis Hampson (Lepidoptera: Noctuidae) and a recent invader, Chilo
      partellus Swinhoe (Lepidoptera: Crambidae). The two braconid parasitoids were the
      native, gregarious larval endoparasitoid Cotesia sesamiae and the recently
      introduced Cotesia flavipes. Both parasitoids attacked both hosts, creating
      evolutionarily old vs. novel interactions. Transient feeding of hosts on
      transgenic maize had various effects on FA, depending on trait as well as the
      host and parasitoid species. These effects were usually stronger in
      evolutionarily novel host-parasitoid associations than in the older, native ones.
      These parameters have capacity to more sensitively indicate the effects of
      potential stressors and merit further consideration.

PMID- 29584708
TI  - Stereoselective Syntheses and Application of Chiral Bi- and Tridentate Ligands
      Derived from (+)-Sabinol.
AB  - A library of bidentate diols, as well as tridentate triols and aminodiols,
      derived from (+)-sabinol, was synthesized in a stereoselective manner. Sabinol
      was transformed into allylic trichloroacetamide via Overman rearrangement of the
      corresponding trichloroacetimidate. After changing the protecting group to Boc,
      the enamine was subjected to stereospecific dihydroxylation with OsO4/NMO,
      resulting in the (1R,2R,3R,5R)-aminodiol diastereomer. The obtained primary
      aminodiol was transformed to a secondary analogue. The ring closure of the N
      benzyl-substituted aminodiol with formaldehyde was investigated and
      regioselective formation of the spiro-oxazolidine ring was observed.
      Hydroboration or dihydroxylation of sabinol or its benzyl ether with OsO4/NMO
      resulted in the formation of sabinane-based diols and triols following a highly
      stereospecific reaction. Treatment of sabinol with m-CPBA afforded O-benzoyl
      triol as a diastereoisomer of the directly dihydroxylated product, instead of the
      expected epoxy alcohol. The resulting aminodiols, diol, and triols were applied
      as chiral catalysts in the reaction of diethylzinc and benzaldehyde from moderate
      to good selectivity.

PMID- 29584707
TI  - MDM2-p53 Interactions in Human Hepatocellular Carcinoma: What Is the Role of
      Nutlins and New Therapeutic Options?
AB  - Human hepatocellular carcinoma (HCC) is the fifth most common cancer and is
      associated with poor prognosis worldwide. The molecular mechanisms underlying the
      pathogenesis of HCC have been an area of continuing interest, and recent studies
      using next generation sequencing (NGS) have revealed much regarding previously
      unsettled issues. Molecular studies using HCC samples have been mainly targeted
      with the aim to identify the fundamental mechanisms contributing to HCC and
      identify more effective treatments. In response to cellular stresses (e.g., DNA
      damage or oncogenes), activated p53 elicits appropriate responses that aim at DNA
      repair, genetic stability, cell cycle arrest, and the deletion of DNA-damaged
      cells. On the other hand, the murine double minute 2 (MDM2) oncogene protein is
      an important cellular antagonist of p53. MDM2 negatively regulates p53 activity
      through the induction of p53 protein degradation. However, current research has
      shown that the mechanisms underlying MDM2-p53 interactions are more complex than
      previously thought. Microarray data have added new insight into the transcription
      changes in HCC. Recently, Nutlin-3 has shown potency against p53-MDM2 binding and
      the enhancement of p53 stabilization as well as an increment of p53 cellular
      accumulation with potential therapeutic effects. This review outlines the
      molecular mechanisms involved in the p53-MDM2 pathways, the biological factors
      influencing these pathways, and their roles in the pathogenesis of HCC. It also
      discusses the action of Nutlin-3 treatment in inducing growth arrest in HCC and
      elaborates on future directions in research in this area. More research on the
      biology of p53-MDM2 interactions may offer a better understanding of these
      mechanisms and discover new biomarkers, sensitive prognostic indicators as well
      as new therapeutic interventions in HCC.

PMID- 29584709
TI  - In Silico Discovery of a Substituted 6-Methoxy-quinalidine with Leishmanicidal
      Activity in Leishmania infantum.
AB  - There is an urgent need for the discovery of new antileishmanial drugs with a new
      mechanism of action. Type 2 NADH dehydrogenase from Leishmania infantum (LiNDH2)
      is an enzyme of the parasite's respiratory system, which catalyzes the electron
      transfer from NADH to ubiquinone without coupled proton pumping. In previous
      studies of the related NADH: ubiquinone oxidoreductase crystal structure from
      Saccharomyces cerevisiae, two ubiquinone-binding sites (UQI and UQII) were
      identified and shown to play an important role in the NDH-2-catalyzed
      oxidoreduction reaction. Based on the available structural data, we developed a
      three-dimensional structural model of LiNDH2 using homology detection methods and
      performed an in silico virtual screening campaign to search for potential
      inhibitors targeting the LiNDH2 ubiquinone-binding site 1-UQI. Selected compounds
      displaying favorable properties in the computational screening experiments were
      assayed for inhibitory activity in the structurally similar recombinant NDH-2
      from S. aureus and leishmanicidal activity was determined in the wild-type axenic
      amastigotes and promastigotes of L. infantum. The identified compound, a
      substituted 6-methoxy-quinalidine, showed promising nanomolar leishmanicidal
      activity on wild-type axenic promastigotes and amastigotes of L. infantum and the
      potential for further development.

PMID- 29584710
TI  - Mobility Enhancement in Amorphous In-Ga-Zn-O Thin-Film Transistor by Induced
      Metallic in Nanoparticles and Cu Electrodes.
AB  - In this work, we fabricated a high-mobility amorphous indium-gallium-zinc-oxide
      (a-IGZO) thin-film transistor (TFT) based on alumina oxide (Al 2 O 3 )
      passivation layer (PVL) and copper (Cu) source/drain electrodes (S/D). The
      mechanism of the high mobility for a-IGZO TFT was proposed and experimentally
      demonstrated. The conductivity of the channel layer was significantly improved
      due to the formation of metallic In nanoparticles on the back channel during Al 2
      O 3 PVL sputtering. In addition, Ar atmosphere annealing induced the Schottky
      contact formation between the Cu S/D and the channel layer caused by Cu
      diffusion. In conjunction with high conductivity channel and Schottky contact,
      the a-IGZO TFT based on Cu S/D and Al 2 O 3 PVL exhibited remarkable mobility of
      33.5-220.1 cm 2 /Vs when channel length varies from 60 to 560 MU m. This work
      presents a feasible way to implement high mobility and Cu electrodes in a-IGZO
      TFT, simultaneously.

PMID- 29584712
TI  - Early career investigator highlight-June.

PMID- 29584711
TI  - Proteomics Analysis to Assess the Role of Mitochondria in BRCA1-Mediated Breast
      Tumorigenesis.
AB  - Mitochondria are the organelles deputed to energy production, but they are also
      involved in carcinogenesis, cancer progression, and metastasis, playing a role in
      altered energy metabolism in cancer cells. Mitochondrial metabolism is connected
      with several mitochondrial pathways such as ROS signaling, Ca2+ homeostasis,
      mitophagy, and mitochondrial biogenesis. These pathways are merged in an
      interactive super-network that seems to play a crucial role in cancer. Germline
      mutations of the BRCA1 gene account for 5-10% of breast cancers and confer a risk
      of developing the disease 10- to 20-fold much higher than in non-carriers. By
      considering metabolic networks that could reconcile both genetic and non-genetic
      causal mechanisms in BRCA1 driven tumorigenesis, we herein based our study on the
      hypothesis that BRCA1 haploinsufficiency might drive metabolic rewiring in breast
      epithelial cells, acting as a push toward malignant transformation. Using 2D-DIGE
      we analyzed and compared the mitochondrial proteomic profile of sporadic breast
      cancer cell line (MCF7) and BRCA1 mutated breast cancer cell line (HCC1937).
      Image analysis was carried out with Decider Software, and proteins differentially
      expressed were identified by LC-MS/MS on a quadrupole-orbitrap mass spectrometer
      Q-Exactive. Ingenuity pathways analysis software was used to analyze the fifty
      three mitochondrial proteins whose expression resulted significantly altered in
      response to BRCA1 mutation status. Mitochondrial Dysfunction and oxidative
      phosphorylation, and energy production and nucleic acid metabolism were,
      respectively, the canonical pathway and the molecular function mainly affected.
      Western blotting analysis was done to validate the expression and the peculiar
      mitochondrial compartmentalization of specific proteins such us HSP60 and HIF
      1alpha. Particularly intriguing is the correlation between BRCA1 mutation status
      and HIF-1alpha localization into the mitochondria in a BRCA1 dependent manner.
      Data obtained led us to hypothesize an interesting connection between BRCA1 and
      mitochondria pathways, capable to trigger metabolic changes, which, in turn,
      sustain the high energetic and anabolic requirements of the malignant phenotype.

PMID- 29584713
TI  - Maternal obesity: a serious pediatric health crisis.

PMID- 29584714
TI  - Clemastine effects in rat models of a myelination disorder.
AB  - BackgroundPelizaeus Merzbacher disease (PMD) is a dysmyelinating disorder of the
      central nervous system caused by impaired differentiation of oligodendrocytes.
      This study was prompted by findings that antimuscarinic compounds enhance
      oligodendrocyte differentiation and remyelination in vitro. One of these
      compounds, clemastine fumarate, is licensed for treatment of allergic conditions.
      We tested whether clemastine fumarate can promote myelination in two rodent PMD
      models, the myelin-deficient and the PLP transgenic rat.MethodsPups were treated
      with daily injections of clemastine (10-30 mg/kg/day) on postnatal days 1-21.
      Neurologic phenotypes and myelination patterns in the brain, optic nerves, and
      spinal cords were assessed using histological techniques.ResultsNo changes in
      neurological phenotype or survival were observed even at the highest dose of
      clemastine. Postmortem staining with Luxol fast blue and myelin basic protein
      immunohistochemistry revealed no evidence for improved myelination in the CNS of
      treated rats compared to vehicle-treated littermates. Populations of mature
      oligodendrocytes were unaffected by the treatment.ConclusionThese results
      demonstrate lack of therapeutic effect of clemastine in two rat PMD models. Both
      models have rapid disease progression consistent with the connatal form of the
      disease. Further studies are necessary to determine whether clemastine bears a
      therapeutic potential in milder forms of PMD.

PMID- 29584715
TI  - What is the value of multidisciplinary care for chronic kidney disease?
AB  - In a Persepctive, Richard Fluck and Maarten Taal discuss the potential value of
      implementing multidisciplinary care programs for chronic kidney disease.

PMID- 29584716
TI  - Evaluation of e-liquid toxicity using an open-source high-throughput screening
      assay.
AB  - The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol
      (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring.
      There are currently over 7,700 e-liquid flavors available, and while some have
      been tested for toxicity in the laboratory, most have not. Here, we developed a 3
      phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly
      triage and validate the toxicity of multiple e-liquids. Our data demonstrated
      that the PG/VG vehicle adversely affected cell viability and that a large number
      of e-liquids were more toxic than PG/VG. We also performed gas chromatography
      mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric
      multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely
      heterogeneous group. Furthermore, these data indicated that (i) the more
      chemicals contained in an e-liquid, the more toxic it was likely to be and (ii)
      the presence of vanillin was associated with higher toxicity values. Further
      analysis of common constituents by electron ionization revealed that the
      concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with
      toxicity. We have also developed a publicly available searchable website
      (www.eliquidinfo.org). Given the large numbers of available e-liquids, this
      website will serve as a resource to facilitate dissemination of this information.
      Our data suggest that an HTS approach to evaluate the toxicity of multiple e
      liquids is feasible. Such an approach may serve as a roadmap to enable bodies
      such as the Food and Drug Administration (FDA) to better regulate e-liquid
      composition.

PMID- 29584717
TI  - Dynamic combination of sensory and reward information under time pressure.
AB  - When making choices, collecting more information is beneficial but comes at the
      cost of sacrificing time that could be allocated to making other potentially
      rewarding decisions. To investigate how the brain balances these costs and
      benefits, we conducted a series of novel experiments in humans and simulated
      various computational models. Under six levels of time pressure, subjects made
      decisions either by integrating sensory information over time or by dynamically
      combining sensory and reward information over time. We found that during sensory
      integration, time pressure reduced performance as the deadline approached, and
      choice was more strongly influenced by the most recent sensory evidence. By
      fitting performance and reaction time with various models we found that our
      experimental results are more compatible with leaky integration of sensory
      information with an urgency signal or a decision process based on stochastic
      transitions between discrete states modulated by an urgency signal. When
      combining sensory and reward information, subjects spent less time on integration
      than optimally prescribed when reward decreased slowly over time, and the most
      recent evidence did not have the maximal influence on choice. The suboptimal
      pattern of reaction time was partially mitigated in an equivalent control
      experiment in which sensory integration over time was not required, indicating
      that the suboptimal response time was influenced by the perception of imperfect
      sensory integration. Meanwhile, during combination of sensory and reward
      information, performance did not drop as the deadline approached, and response
      time was not different between correct and incorrect trials. These results
      indicate a decision process different from what is involved in the integration of
      sensory information over time. Together, our results not only reveal limitations
      in sensory integration over time but also illustrate how these limitations
      influence dynamic combination of sensory and reward information.

PMID- 29584718
TI  - Rapid evolution of a voltage-gated sodium channel gene in a lineage of electric
      fish leads to a persistent sodium current.
AB  - Most weakly electric fish navigate and communicate by sensing electric signals
      generated by their muscle-derived electric organs. Adults of one lineage
      (Apteronotidae), which discharge their electric organs in excess of 1 kHz,
      instead have an electric organ derived from the axons of specialized spinal
      neurons (electromotorneurons [EMNs]). EMNs fire spontaneously and are the fastest
      firing neurons known. This biophysically extreme phenotype depends upon a
      persistent sodium current, the molecular underpinnings of which remain unknown.
      We show that a skeletal muscle-specific sodium channel gene duplicated in this
      lineage and, within approximately 2 million years, began expressing in the spinal
      cord, a novel site of expression for this isoform. Concurrently, amino acid
      replacements that cause a persistent sodium current accumulated in the regions of
      the channel underlying inactivation. Therefore, a novel adaptation allowing
      extreme neuronal firing arose from the duplication, change in expression, and
      rapid sequence evolution of a muscle-expressing sodium channel gene.

PMID- 29584719
TI  - Dynamic cues for whisker-based object localization: An analytical solution to
      vibration during active whisker touch.
AB  - Vibrations are important cues for tactile perception across species. Whisker
      based sensation in mice is a powerful model system for investigating mechanisms
      of tactile perception. However, the role vibration plays in whisker-based
      sensation remains unsettled, in part due to difficulties in modeling the
      vibration of whiskers. Here, we develop an analytical approach to calculate the
      vibrations of whiskers striking objects. We use this approach to quantify
      vibration forces during active whisker touch at a range of locations along the
      whisker. The frequency and amplitude of vibrations evoked by contact are strongly
      dependent on the position of contact along the whisker. The magnitude of
      vibrational shear force and bending moment is comparable to quasi-static forces.
      The fundamental vibration frequencies are in a detectable range for
      mechanoreceptor properties and below the maximum spike rates of primary sensory
      afferents. These results suggest two dynamic cues exist that rodents can use for
      object localization: vibration frequency and comparison of vibrational to quasi
      static force magnitude. These complement the use of quasi-static force angle as a
      distance cue, particularly for touches close to the follicle, where whiskers are
      stiff and force angles hardly change during touch. Our approach also provides a
      general solution to calculation of whisker vibrations in other sensing tasks.

PMID- 29584720
TI  - Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney
      disease in the United States: A modeling study.
AB  - BACKGROUND: Multidisciplinary care (MDC) programs have been proposed as a way to
      alleviate the cost and morbidity associated with chronic kidney disease (CKD) in
      the US. METHODS AND FINDINGS: We assessed the cost-effectiveness of a theoretical
      Medicare-based MDC program for CKD compared to usual CKD care in Medicare
      beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The
      program used nephrologists, advanced practitioners, educators, dieticians, and
      social workers. From Medicare claims and published literature, we developed a
      novel deterministic Markov model for CKD progression and calibrated it to long
      term risks of mortality and progression to end-stage renal disease. We then used
      the model to project accrued discounted costs and quality-adjusted life years
      (QALYs) over patients' remaining lifetime. We estimated the incremental cost
      effectiveness ratio (ICER) of MDC, or the cost of the intervention per QALY
      gained. MDC added 0.23 (95% CI: 0.08, 0.42) QALYs over usual care, costing
      $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of
      $150,000 per QALY gained; 95% CI: $6,252, $44,323). In all subpopulations
      analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally
      more cost-effective in patients with higher urine albumin excretion. Although
      ICERs were higher in younger patients, MDC could yield greater improvements in
      health in younger than older patients. MDC remained cost-effective when we
      decreased its effectiveness to 25% of the base case or increased the cost 5-fold.
      The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity
      analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our
      study include its theoretical nature and being less generalizable to populations
      at low risk for progression to ESRD. We did not study the potential impact of MDC
      on hospitalization (cardiovascular or other). CONCLUSIONS: Our model estimates
      that a Medicare-funded MDC program could reduce the need for dialysis, prolong
      life expectancy, and meet conventional cost-effectiveness thresholds in middle
      aged to elderly patients with mild to moderate CKD.

PMID- 29584721
TI  - Multimorbidity in patients with heart failure from 11 Asian regions: A
      prospective cohort study using the ASIAN-HF registry.
AB  - BACKGROUND: Comorbidities are common in patients with heart failure (HF) and
      complicate treatment and outcomes. We identified patterns of multimorbidity in
      Asian patients with HF and their association with patients' quality of life (QoL)
      and health outcomes. METHODS AND FINDINGS: We used data on 6,480 patients with
      chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October
      2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN
      HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients
      prospectively enrolled from in- and outpatient clinics from 11 Asian regions
      (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore,
      Indonesia, and Philippines). Latent class analysis was used to identify patterns
      of multimorbidity. The primary outcome was defined as a composite of all-cause
      mortality or HF hospitalization within 1 year. To assess differences in QoL, we
      used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct
      multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more
      AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759;
      youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261;
      ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low
      prevalence of obesity, high prevalence of chronic kidney disease). Patients in
      the lean diabetic group had the worst QoL, more severe signs and symptoms of HF,
      and the highest rate of the primary combined outcome within 1 year (29% versus
      11% in the young group) (p for all <0.001). Adjusting for confounders
      (demographics, New York Heart Association class, and medication) the lean
      diabetic (hazard ratio [HR] 1.79, 95% CI 1.46-2.22), elderly/AF (HR 1.57, 95% CI
      1.26-1.96), ischemic (HR 1.51, 95% CI 1.22-1.88), and metabolic (HR 1.28, 95% CI
      1.02-1.60) groups had higher rates of the primary combined outcome compared to
      the young group. Potential limitations include site selection and participation
      bias. CONCLUSIONS: Among Asian patients with HF, comorbidities naturally
      clustered in 5 distinct patterns, each differentially impacting patients' QoL and
      health outcomes. These data underscore the importance of studying multimorbidity
      in HF and the need for more comprehensive approaches in phenotyping patients with
      HF and multimorbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01633398.

PMID- 29584722
TI  - PIKfyve regulates melanosome biogenesis.
AB  - PIKfyve, VAC14, and FIG4 form a complex that catalyzes the production of
      PI(3,5)P2, a signaling lipid implicated in process ranging from lysosome
      maturation to neurodegeneration. While previous studies have identified VAC14 and
      FIG4 mutations that lead to both neurodegeneration and coat color defects, how
      PIKfyve regulates melanogenesis is unknown. In this study, we sought to better
      understand the role of PIKfyve in melanosome biogenesis. Melanocyte-specific
      PIKfyve knockout mice exhibit greying of the mouse coat and the accumulation of
      single membrane vesicle structures in melanocytes resembling multivesicular
      endosomes. PIKfyve inhibition blocks melanosome maturation, the processing of the
      melanosome protein PMEL, and the trafficking of the melanosome protein TYRP1.
      Taken together, these studies identify a novel role for PIKfyve in controlling
      the delivery of proteins from the endosomal compartment to the melanosome, a role
      that is distinct from the role of PIKfyve in the reformation of lysosomes from
      endolysosomes.

PMID- 29584723
TI  - Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross
      sectional study of a primary HIV infection cohort.
AB  - BACKGROUND: Transmission of human immunodeficiency virus type 1 (HIV-1) drug
      resistance mutations, particularly that of minority drug-resistant variants,
      remains poorly understood. Population-based studies suggest that drug-resistant
      HIV-1 is less transmissible than drug-susceptible viruses. We compared HIV-1 drug
      resistant genotypes among partner-pairs in order to assess the likelihood of
      transmission of drug resistance mutations and investigate the role of minority
      variants in HIV transmission. METHODS AND FINDINGS: From 1992-2010, 340 persons
      with primary HIV-1 infection and their partners were enrolled into observational
      research studies at the University of Washington Primary Infection Clinic
      (UWPIC). Out of 50 partner-pairs enrolled, 36 (72%) transmission relationships
      were confirmed by phylogenetic distance analysis of HIV-1 envelope (env)
      sequences, and 31 partner-pairs enrolled after 1995 met criteria for this study.
      Drug resistance mutations in the region of the HIV-1 polymerase gene (pol) that
      encodes protease and reverse transcriptase were assessed by 454-pyrosequencing.
      In 25 partner-pairs where the transmission direction could be determined, 12
      (48%) transmitters had 1-4 drug resistance mutations (23 total) detected in their
      HIV-1 populations at a median frequency of 6.0% (IQR 1.5%-98.7%, range 1.0%
      99.6%). Of 10 major mutations detected in five transmitters at a frequency >95%,
      100% (95% CI 69.2%-100%) were detected in recipients. All of these transmitters
      were antiretroviral (ARV)-naive at the time of specimen collection. Fourteen
      mutations (eight major mutations and six accessory mutations) were detected in
      nine transmitters at low frequencies (1.0%-11.8%); four of these transmitters had
      previously received ARV therapy. Two (14% [95% CI 1.8%-42.8%]) G73S accessory
      mutations were detected in both transmitter and recipient. This number is not
      significantly different from the number expected based on the observed
      frequencies of drug-resistant viruses in transmitting partners. Limitations of
      this study include the small sample size and uncertainties in determining the
      timing of virus transmission and mutation history. CONCLUSIONS: Drug-resistant
      majority variants appeared to be commonly transmitted by ARV-naive participants
      in our analysis and may contribute significantly to transmitted drug resistance
      on a population level. When present at low frequency, no major mutation was
      observed to be shared between partner-pairs; identification of accessory
      mutations shared within a pair could be due to transmission, laboratory artifact,
      or apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBECs), and
      warrants further study.

PMID- 29584724
TI  - Developing a Buruli ulcer community of practice in Bankim, Cameroon: A model for
      Buruli ulcer outreach in Africa.
AB  - BACKGROUND: In the Cameroon, previous efforts to identify Buruli ulcer (BU)
      through the mobilization of community health workers (CHWs) yielded poor results.
      In this paper, we describe the successful creation of a BU community of practice
      (BUCOP) in Bankim, Cameroon composed of hospital staff, former patients, CHWs,
      and traditional healers. METHODS AND PRINCIPLE FINDINGS: All seven stages of a
      well-defined formative research process were conducted during three phases of
      research carried out by a team of social scientists working closely with Bankim
      hospital staff. Phase one ethnographic research generated interventions tested in
      a phase two proof of concept study followed by a three- year pilot project. In
      phase three the pilot project was evaluated. An outcome evaluation documented a
      significant rise in BU detection, especially category I cases, and a shift in
      case referral. Trained CHW and traditional healers initially referred most
      suspected cases of BU to Bankim hospital. Over time, household members exposed to
      an innovative and culturally sensitive outreach education program referred the
      greatest number of suspected cases. Laboratory confirmation of suspected BU cases
      referred by community stakeholders was above 30%. An impact and process
      evaluation found that sustained collaboration between health staff, CHWs, and
      traditional healers had been achieved. CHWs came to play a more active role in
      organizing BU outreach activities, which increased their social status.
      Traditional healers found they gained more from collaboration than they lost from
      referral. CONCLUSION/ SIGNIFICANCE: Setting up lines of communication, and
      promoting collaboration and trust between community stakeholders and health staff
      is essential to the control of neglected tropical diseases. It is also essential
      to health system strengthening and emerging disease preparedness. The BUCOP model
      described in this paper holds great promise for bringing communities together to
      solve pressing health problems in a culturally sensitive manner.

PMID- 29584726
TI  - Comparative analysis of the association between 35 frailty scores and
      cardiovascular events, cancer, and total mortality in an elderly general
      population in England: An observational study.
AB  - BACKGROUND: Frail elderly people experience elevated mortality. However, no
      consensus exists on the definition of frailty, and many frailty scores have been
      developed. The main aim of this study was to compare the association between 35
      frailty scores and incident cardiovascular disease (CVD), incident cancer, and
      all-cause mortality. Also, we aimed to assess whether frailty scores added
      predictive value to basic and adjusted models for these outcomes. METHODS AND
      FINDINGS: Through a structured literature search, we identified 35 frailty scores
      that could be calculated at wave 2 of the English Longitudinal Study of Ageing
      (ELSA), an observational cohort study. We analysed data from 5,294 participants,
      44.9% men, aged 60 years and over. We studied the association between each of the
      scores and the incidence of CVD, cancer, and all-cause mortality during a 7-year
      follow-up using Cox proportional hazard models at progressive levels of
      adjustment. We also examined the added predictive performance of each score on
      top of basic models using Harrell's C statistic. Using age of the participant as
      a timescale, in sex-adjusted models, hazard ratios (HRs) (95% confidence
      intervals) for all-cause mortality ranged from 2.4 (95% CI: 1.7-3.3) to 26.2 (95%
      CI: 15.4-44.5). In further adjusted models including smoking status and alcohol
      consumption, HR ranged from 2.3 (95% CI: 1.6-3.1) to 20.2 (95% CI: 11.8-34.5). In
      fully adjusted models including lifestyle and comorbidity, HR ranged from 0.9
      (95% CI: 0.5-1.7) to 8.4 (95% CI: 4.9-14.4). HRs for CVD and cancer incidence in
      sex-adjusted models ranged from 1.2 (95% CI: 0.5-3.2) to 16.5 (95% CI: 7.8-35.0)
      and from 0.7 (95% CI: 0.4-1.2) to 2.4 (95% CI: 1.0-5.7), respectively. In sex-
      and age-adjusted models, all frailty scores showed significant added predictive
      performance for all-cause mortality, increasing the C statistic by up to 3%. None
      of the scores significantly improved basic prediction models for CVD or cancer. A
      source of bias could be the differences in mortality follow-up time compared to
      CVD/cancer, because the existence of informative censoring cannot be excluded.
      CONCLUSION: There is high variability in the strength of the association between
      frailty scores and 7-year all-cause mortality, incident CVD, and cancer. With
      regard to all-cause mortality, some scores give a modest improvement to the
      predictive ability. Our results show that certain scores clearly outperform
      others with regard to three important health outcomes in later life. Finally, we
      think that despite their limitations, the use of frailty scores to identify the
      elderly population at risk is still a useful measure, and the choice of a frailty
      score should balance feasibility with performance.

PMID- 29584725
TI  - Prevalence of metabolic syndrome and its risk factors in Kerala, South India:
      Analysis of a community based cross-sectional study.
AB  - BACKGROUND: Coronary Artery Disease (CAD) is a leading cause of death and
      disability in Kerala, India. Metabolic syndrome (MS) is a constellation of
      established risk factors for CAD. We aimed to estimate the prevalence of MS and
      evaluate the association between MS and CAD using a community-based sample
      population. METHODS: A cross-sectional community based survey was conducted in
      urban and rural areas of Kerala in 2011. We included 5063 individuals for
      analysis. Age standardized prevalence of MS, associated diagnoses (hypertension,
      diabetes and hypercholesterolemia) and other potential risk factors were assessed
      for men and women in both urban and rural locations. Univariate and multivariate
      logistic regression models were developed to identify participant characteristics
      that are associated with MS. RESULTS: After standardization for age and
      adjustment for sex and urban-rural distribution, the prevalence of metabolic
      syndrome in Kerala was 24%, 29% and 33% for the NCEP ATP III, IDF and AHA/NHLBI
      Harmonization definitions, respectively. The mean (SD) age of the participants
      was 51 (14) years, and 60% were women. Women had a higher prevalence of MS than
      men (28% versus 20% for ATP III, p<0.001). Similarly, participants living in
      urban areas had higher prevalence of MS than their rural counterparts (26% versus
      22%, p<0.001). Elevated body mass index, older age, and female sex were
      associated with MS in an adjusted multivariate model. The propensity for definite
      CAD was 1.7 times higher in individuals with MS defined based on ATP III criteria
      compared to those without MS (Adjusted OR = 1.69; 95% CI: 1.3-2.2, p<0.001).
      CONCLUSIONS: One of four to one of three adult individuals in Kerala have MS
      based on different criteria. Higher propensity for CAD in individuals with MS in
      Kerala calls for urgent steps to prevent and control the burden of metabolic
      conditions.

PMID- 29584727
TI  - Determinants of delay in timely treatment seeking for diarrheal diseases among
      mothers with under-five children in central Ethiopia: A case control study.
AB  - BACKGROUND: Delays in seeking timely appropriate care contributes to a large
      number of deaths from diarrhea in children. This study aimed to identify
      determinants of delays in seeking timely treatment by mothers/caregivers of under
      five children with diarrheal diseases. METHODS: We used an unmatched case-control
      study from February-March 2017 among 316 children: 158 cases and 158 controls.
      Cases were mothers/caregivers with under-five children who had signs/symptoms of
      diarrhea and sought treatment after 24 hours onset of symptom. Controls sought
      treatment within 24 hours. Field workers collected data using a pre-tested
      standardized questionnaire. Multivariate logistic regression was conducted to
      identify determinants of delay in timely diarrhea treatment seeking. Statistical
      significance was declared by using a p-value<0.05 and 95% of confidence interval
      (CI) for an adjusted-odds ratio (AOR). RESULTS: The determinants of delay in
      timely treatment seeking of mothers/caregivers of under-five children with
      diarrheal diseases were children <24months (AOR = 1.9,95%CI:1.1-3.4); fail to
      attend school (AOR = 2.4, 95%CI:1.2-4.6); being female children (AOR =
      1.7,95%CI:1.05-2.9); preferring government health facility for the treatment of
      children with diarrheal diseases (AOR = 2.9, 95%CI, 1.3-6.7); lack of past
      history taking children to health facility and lack of counseling (AOR = 4.8,
      95%CI:2.0-12.1); being in the15-25 years age (AOR = 1.7, 95%CI:1.1-3.0) and
      taking children to a health facility as a first response to diarrhea (AOR = 0.1,
      95%CI:0.01-0.8). CONCLUSIONS: Age of the child, maternal age, and disease related
      determinants were determinants for seeking timely treatment to diarrheal
      diseases. Providing skilled based health education and counseling to
      mothers/caregivers on seeking timely treatment and taking children with diarrheal
      diseases to a health facility as a first response to diarrhea is a paramount
      intervention to reduce morbidity and mortality of children.

PMID- 29584728
TI  - Bifurcation analysis of two coupled Jansen-Rit neural mass models.
AB  - We investigate how changes in network structure can lead to pathological
      oscillations similar to those observed in epileptic brain. Specifically, we
      conduct a bifurcation analysis of a network of two Jansen-Rit neural mass models,
      representing two cortical regions, to investigate different aspects of its
      behavior with respect to changes in the input and interconnection gains. The
      bifurcation diagrams, along with simulated EEG time series, exhibit diverse
      behaviors when varying the input, coupling strength, and network structure. We
      show that this simple network of neural mass models can generate various
      oscillatory activities, including delta wave activity, which has not been
      previously reported through analysis of a single Jansen-Rit neural mass model.
      Our analysis shows that spike-wave discharges can occur in a cortical region as a
      result of input changes in the other region, which may have important
      implications for epilepsy treatment. The bifurcation analysis is related to
      clinical data in two case studies.

PMID- 29584729
TI  - Exact and heuristic algorithms for Space Information Flow.
AB  - Space Information Flow (SIF) is a new promising research area that studies
      network coding in geometric space, such as Euclidean space. The design of
      algorithms that compute the optimal SIF solutions remains one of the key open
      problems in SIF. This work proposes the first exact SIF algorithm and a heuristic
      SIF algorithm that compute min-cost multicast network coding for N (N >= 3) given
      terminal nodes in 2-D Euclidean space. Furthermore, we find that the Butterfly
      network in Euclidean space is the second example besides the Pentagram network
      where SIF is strictly better than Euclidean Steiner minimal tree. The exact
      algorithm design is based on two key techniques: Delaunay triangulation and
      linear programming. Delaunay triangulation technique helps to find practically
      good candidate relay nodes, after which a min-cost multicast linear programming
      model is solved over the terminal nodes and the candidate relay nodes, to compute
      the optimal multicast network topology, including the optimal relay nodes
      selected by linear programming from all the candidate relay nodes and the flow
      rates on the connection links. The heuristic algorithm design is also based on
      Delaunay triangulation and linear programming techniques. The exact algorithm can
      achieve the optimal SIF solution with an exponential computational complexity,
      while the heuristic algorithm can achieve the sub-optimal SIF solution with a
      polynomial computational complexity. We prove the correctness of the exact SIF
      algorithm. The simulation results show the effectiveness of the heuristic SIF
      algorithm.

PMID- 29584731
TI  - Cardiovascular disease and multimorbidity: A call for interdisciplinary research
      and personalized cardiovascular care.
AB  - In a Guest Editorial, Kazem Rahimi, Carolyn Lam, and Steven Steinhubl call for
      interdisciplinary research and personalized cardiovascular care to better manage
      patients with cardiovascular disease and multimorbidity.

PMID- 29584730
TI  - Antiviral efficacy of favipiravir against Ebola virus: A translational study in
      cynomolgus macaques.
AB  - BACKGROUND: Despite repeated outbreaks, in particular the devastating 2014-2016
      epidemic, there is no effective treatment validated for patients with Ebola virus
      disease (EVD). Among the drug candidates is the broad-spectrum polymerase
      inhibitor favipiravir, which showed a good tolerance profile in patients with EVD
      (JIKI trial) but did not demonstrate a strong antiviral efficacy. In order to
      gain new insights into the antiviral efficacy of favipiravir and improve
      preparedness and public health management of future outbreaks, we assess the
      efficacy achieved by ascending doses of favipiravir in Ebola-virus-infected
      nonhuman primates (NHPs). METHODS AND FINDINGS: A total of 26 animals (Macaca
      fascicularis) were challenged intramuscularly at day 0 with 1,000 focus-forming
      units of Ebola virus Gabon 2001 strain and followed for 21 days (study
      termination). This included 13 animals left untreated and 13 treated with doses
      of 100, 150, and 180 mg/kg (N = 3, 5, and 5, respectively) favipiravir
      administered intravenously twice a day for 14 days, starting 2 days before
      infection. All animals left untreated or treated with 100 mg/kg died within 10
      days post-infection, while animals receiving 150 and 180 mg/kg had extended
      survival (P < 0.001 and 0.001, respectively, compared to untreated animals),
      leading to a survival rate of 40% (2/5) and 60% (3/5), respectively, at day 21.
      Favipiravir inhibited viral replication (molecular and infectious viral loads) in
      a drug-concentration-dependent manner (P values < 0.001), and genomic deep
      sequencing analyses showed an increase in virus mutagenesis over time. These
      results allowed us to identify that plasma trough favipiravir concentrations
      greater than 70-80 MUg/ml were associated with reduced viral loads, lower virus
      infectivity, and extended survival. These levels are higher than those found in
      the JIKI trial, where patients had median trough drug concentrations equal to 46
      and 26 MUg/ml at day 2 and day 4 post-treatment, respectively, and suggest that
      the dosing regimen in the JIKI trial was suboptimal. The environment of a
      biosafety level 4 laboratory introduces a number of limitations, in particular
      the difficulty of conducting blind studies and performing detailed
      pharmacological assessments. Further, the extrapolation of the results to
      patients with EVD is limited by the fact that the model is fully lethal and that
      treatment initiation in patients with EVD is most often initiated several days
      after infection, when symptoms and high levels of viral replication are already
      present. CONCLUSIONS: Our results suggest that favipiravir may be an effective
      antiviral drug against Ebola virus that relies on RNA chain termination and
      possibly error catastrophe. These results, together with previous data collected
      on tolerance and pharmacokinetics in both NHPs and humans, support a potential
      role for high doses of favipiravir for future human interventions.

PMID- 29584732
TI  - Wood-boring beetles associated with Acacia xanthophloea in Nairobi and Machakos
      Counties, Kenya.
AB  - Naivasha thorn tree, Acacia xanthophloea, is grown for foliage, timber, shade and
      rehabilitation of soils in areas with high water tables in Kenya. Its production
      is threatened by insect pests, which cause major losses. Very little is
      documented on wood-boring beetles which cause considerable economic damage to
      lumber used in a variety of applications, and little is known about their natural
      enemies in Kenya. We conducted the study to evaluate the occurrence of wood
      boring beetles on A. xanthophloea in two different regions of Kenya. Infested
      wood samples of A. xanthophloea with fresh exit holes were collected from three
      sites in Kenyatta University (KU), Nairobi and Mitaboni in Machakos, Kenya. The
      samples were placed in clear plastic buckets and kept at ambient temperatures
      23+/-2 degrees C, 65+/-10% relative humidity and 12L: 12D in a laboratory where
      they were observed daily for adult emergence. Adult beetles were collected every
      three days for identification and data recording. The experiment was replicated
      four times and data collected twice a week for 6 months. Data on abundance was
      subjected to analysis of variance using SAS software. A total of 5,850 and 4,691
      beetles were collected where 2,187 and 3,097 were Bostrichidae, accounting for
      37% and 66% in KU and Mitaboni, respectively. A total of 12 bostrichid species
      was identified, including Sinoxylon ruficorne, S. doliolum, Xylion adustus,
      Xyloperthodes nitidipennis, Xyloperthella picea, Xylopsocus castanoptera, Lyctus
      brunneus, Heterbostrychus brunneus, Xylopsocus sp., and Dinoderus gabonicus. The
      most abundant species in KU was Xylion adustus with 1,915 beetles accounting for
      88.4%, and Sinoxylon ruficorne in Mitaboni with 1,050 beetles accounting for
      33.9% of the total. Sinoxylon ruficorne was only recorded in Mitaboni while only
      2 specimens of D. gabonicus were found in KU. The mean number of exit holes on A.
      xanthophloea differed significantly between sites, which corresponded
      approximately to the amount of economic damage caused by the beetles to the
      structural integrity of the lumber. In addition, a number of predators in the
      family Cerambycidae, Cleridae, Histeridae and parasitoids from Braconidae,
      Ichneumonidae, and Chalcididae were recovered, suggesting a need to conduct
      further studies to document these species' diversity, parasitism rates and
      efficacy for possible biological control.

PMID- 29584734
TI  - Comorbidity health pathways in heart failure patients: A sequences-of-regressions
      analysis using cross-sectional data from 10,575 patients in the Swedish Heart
      Failure Registry.
AB  - BACKGROUND: Optimally treated heart failure (HF) patients often have persisting
      symptoms and poor health-related quality of life. Comorbidities are common, but
      little is known about their impact on these factors, and guideline-driven HF care
      remains focused on cardiovascular status. The following hypotheses were tested:
      (i) comorbidities are associated with more severe symptoms and functional
      limitations and subsequently worse patient-rated health in HF, and (ii) these
      patterns of association differ among selected comorbidities. METHODS AND
      FINDINGS: The Swedish Heart Failure Registry (SHFR) is a national population
      based register of HF patients admitted to >85% of hospitals in Sweden or
      attending outpatient clinics. This study included 10,575 HF patients with patient
      rated health recorded during first registration in the SHFR (1 February 2008 to 1
      November 2013). An a priori health model and sequences-of-regressions analysis
      were used to test associations among comorbidities and patient-reported symptoms,
      functional limitations, and patient-rated health. Patient-rated health measures
      included the EuroQol-5 dimension (EQ-5D) questionnaire and the EuroQol visual
      analogue scale (EQ-VAS). EQ-VAS score ranges from 0 (worst health) to 100 (best
      health). Patient-rated health declined progressively from patients with no
      comorbidities (mean EQ-VAS score, 66) to patients with cardiovascular
      comorbidities (mean EQ-VAS score, 62) to patients with non-cardiovascular
      comorbidities (mean EQ-VAS score, 59). The relationships among cardiovascular
      comorbidities and patient-rated health were explained by their associations with
      anxiety or depression (atrial fibrillation, odds ratio [OR] 1.16, 95% CI 1.06 to
      1.27; ischemic heart disease [IHD], OR 1.20, 95% CI 1.09 to 1.32) and with pain
      (IHD, OR 1.25, 95% CI 1.14 to 1.38). Associations of non-cardiovascular
      comorbidities with patient-rated health were explained by their associations with
      shortness of breath (diabetes, OR 1.17, 95% CI 1.03 to 1.32; chronic kidney
      disease [CKD, OR 1.23, 95% CI 1.10 to 1.38; chronic obstructive pulmonary disease
      [COPD], OR 95% CI 1.84, 1.62 to 2.10) and with fatigue (diabetes, OR 1.27, 95% CI
      1.13 to 1.42; CKD, OR 1.24, 95% CI 1.12 to 1.38; COPD, OR 1.69, 95% CI 1.50 to
      1.91). There were direct associations between all symptoms and patient-rated
      health, and indirect associations via functional limitations. Anxiety or
      depression had the strongest association with functional limitations (OR 10.03,
      95% CI 5.16 to 19.50) and patient-rated health (mean difference in EQ-VAS score, 
      18.68, 95% CI -23.22 to -14.14). HF optimizing therapies did not influence these
      associations. Key limitations of the study include the cross-sectional design and
      unclear generalisability to other populations. Further prospective HF studies are
      required to test the consistency of the relationships and their implications for
      health. CONCLUSIONS: Identification of distinct comorbidity health pathways in HF
      could provide the evidence for individualised person-centred care that targets
      specific comorbidities and associated symptoms.

PMID- 29584733
TI  - Experimental evolution of diverse Escherichia coli metabolic mutants identifies
      genetic loci for convergent adaptation of growth rate.
AB  - Cell growth is determined by substrate availability and the cell's metabolic
      capacity to assimilate substrates into building blocks. Metabolic genes that
      determine growth rate may interact synergistically or antagonistically, and can
      accelerate or slow growth, depending on genetic background and environmental
      conditions. We evolved a diverse set of Escherichia coli single-gene deletion
      mutants with a spectrum of growth rates and identified mutations that generally
      increase growth rate. Despite the metabolic differences between parent strains,
      mutations that enhanced growth largely mapped to core transcription machinery,
      including the beta and beta' subunits of RNA polymerase (RNAP) and the
      transcription elongation factor, NusA. The structural segments of RNAP that
      determine enhanced growth have been previously implicated in antibiotic
      resistance and in the control of transcription elongation and pausing. We further
      developed a computational framework to characterize how the transcriptional
      changes that occur upon acquisition of these mutations affect growth rate across
      strains. Our experimental and computational results provide evidence for cases in
      which RNAP mutations shift the competitive balance between active transcription
      and gene silencing. This study demonstrates that mutations in specific regions of
      RNAP are a convergent adaptive solution that can enhance the growth rate of cells
      from distinct metabolic states.

PMID- 29584735
TI  - Prospective memory, retrospective memory, and individual differences in cognitive
      abilities, personality, and psychopathology.
AB  - Although individual differences in processing speed, working memory,
      intelligence, and other cognitive functions were found to explain individual
      differences in retrospective memory (RetM), much less is known about their
      relationship with prospective memory (ProM). Moreover, the studies that
      investigated the relationship between ProM and cognitive functions arrived to
      contradictory conclusions. The relationship between ProM, personality, and
      psychopathology is similarly unsettled. Meta-analytic reviews of the
      relationships of ProM with aging and personality suggest that the contradictory
      findings may be due to widespread methodological problems plaguing ProM research
      including the prevalent use of inefficient, unreliable binary measures;
      widespread ceiling effects; failure to distinguish between various ProM
      subdomains (e.g., episodic ProM versus vigilance/monitoring); various confounds;
      and, importantly, small sample sizes, resulting in insufficient statistical
      power. Accordingly, in a large scale study with nearly 1,200 participants, we
      investigated the relationship between episodic event-cued ProM, episodic RetM,
      and fundamental cognitive functions including intelligence, personality, and
      psychopathology, using reliable continuous measures of episodic event-cued ProM.
      Our findings show that (a) continuous measures of episodic event-cued ProM were
      much more reliable than binary measures, (b) episodic event-cued ProM was
      associated with measures of processing speed, working memory, crystallized and
      fluid intelligence, as well as RetM, and that such associations were similar for
      ProM and RetM, (c) personality factors did not improve prediction of neither ProM
      nor RetM beyond the variance predicted by cognitive ability, (d) symptoms of
      psychopathology did not improve the prediction of ProM although they slightly
      improved the prediction of RetM, and (e) participants' sex was not associated
      with ProM but showed small correlations with RetM. In addition to advancing our
      theoretical understanding of ProM, our findings highlight the need to avoid
      common pitfalls plaguing ProM research.

PMID- 29584737
TI  - Nictitating membrane fixation improves stability of the contact lens on the
      animal corneal surface.
AB  - We evaluated the feasibility and safety of nictitating membrane fixation to
      address reduced contact lens stability by the nictitating membrane in a rabbit
      model. Under general anesthesia, twelve animals received a horizontal mattress
      suture between the nictitating membrane and the upper eyelid of one eye. To
      assess the effects of this technique and secondary side effects, contact lens
      stability test, Schirmer tear test, tear break-up time measurement, eye tissue
      pathology and morphology were evaluated. Contact lens stability was increased
      after nictitating membrane fixation. The percentage of contact lens retention in
      the nictitating membrane fixed rabbit after 4 hours was 90% whereas that in the
      untreated rabbit was 42.5%. In addition, there were no significant differences in
      tear quantity and quality between the fixed and untreated eyes. Furthermore, no
      remarkable pathological lesions were found in gross observation during the 1
      month time period or the following pathological examination. In this study, we
      demonstrated that nictitating membrane fixation increases contact lens stability
      without specific side effects using a rabbit model. This minimally invasive
      procedure could be useful when designing animal models for testing new contact
      lenses and has potential to apply to other biomaterial research on the ocular
      surface.

PMID- 29584736
TI  - Population genomics of Fusarium graminearum reveals signatures of divergent
      evolution within a major cereal pathogen.
AB  - The cereal pathogen Fusarium graminearum is the primary cause of Fusarium head
      blight (FHB) and a significant threat to food safety and crop production. To
      elucidate population structure and identify genomic targets of selection within
      major FHB pathogen populations in North America we sequenced the genomes of 60
      diverse F. graminearum isolates. We also assembled the first pan-genome for F.
      graminearum to clarify population-level differences in gene content potentially
      contributing to pathogen diversity. Bayesian and phylogenomic analyses revealed
      genetic structure associated with isolates that produce the novel NX-2 mycotoxin,
      suggesting a North American population that has remained genetically distinct
      from other endemic and introduced cereal-infecting populations. Genome scans
      uncovered distinct signatures of selection within populations, focused in high
      diversity, frequently recombining regions. These patterns suggested selection for
      genomic divergence at the trichothecene toxin gene cluster and thirteen
      additional regions containing genes potentially involved in pathogen
      specialization. Gene content differences further distinguished populations, in
      that 121 genes showed population-specific patterns of conservation. Genes that
      differentiated populations had predicted functions related to pathogenesis,
      secondary metabolism and antagonistic interactions, though a subset had unique
      roles in temperature and light sensitivity. Our results indicated that F.
      graminearum populations are distinguished by dozens of genes with signatures of
      selection and an array of dispensable accessory genes, suggesting that FHB
      pathogen populations may be equipped with different traits to exploit the
      agroecosystem. These findings provide insights into the evolutionary processes
      and genomic features contributing to population divergence in plant pathogens,
      and highlight candidate genes for future functional studies of pathogen
      specialization across evolutionarily and ecologically diverse fungi.

PMID- 29584738
TI  - Conveying facial expressions to blind and visually impaired persons through a
      wearable vibrotactile device.
AB  - In face-to-face social interactions, blind and visually impaired persons (VIPs)
      lack access to nonverbal cues like facial expressions, body posture, and
      gestures, which may lead to impaired interpersonal communication. In this study,
      a wearable sensory substitution device (SSD) consisting of a head mounted camera
      and a haptic belt was evaluated to determine whether vibrotactile cues around the
      waist could be used to convey facial expressions to users and whether such a
      device is desired by VIPs for use in daily living situations. Ten VIPs (mean age:
      38.8, SD: 14.4) and 10 sighted persons (SPs) (mean age: 44.5, SD: 19.6)
      participated in the study, in which validated sets of pictures, silent videos,
      and videos with audio of facial expressions were presented to the participant. A
      control measurement was first performed to determine how accurately participants
      could identify facial expressions while relying on their functional senses. After
      a short training, participants were asked to determine facial expressions while
      wearing the emotion feedback system. VIPs using the device showed significant
      improvements in their ability to determine which facial expressions were shown. A
      significant increase in accuracy of 44.4% was found across all types of stimuli
      when comparing the scores of the control (mean+/-SEM: 35.0+/-2.5%) and supported
      (mean+/-SEM: 79.4+/-2.1%) phases. The greatest improvements achieved with the
      support of the SSD were found for silent stimuli (68.3% for pictures and 50.8%
      for silent videos). SPs also showed consistent, though not statistically
      significant, improvements while supported. Overall, our study shows that
      vibrotactile cues are well suited to convey facial expressions to VIPs in real
      time. Participants became skilled with the device after a short training session.
      Further testing and development of the SSD is required to improve its accuracy
      and aesthetics for potential daily use.

PMID- 29584739
TI  - Could HE4 level measurements during first-line chemotherapy predict response to
      treatment among ovarian cancer patients?
AB  - BACKGROUND: This study assessed the prognostic value of HE4 marker measurements
      at various stages of first-line chemotherapy for ovarian cancer. METHODS: The
      study consisted of 90 ovarian cancer patients, including 48 women undergoing
      primary surgical treatment and 42 patients qualified for neoadjuvant
      chemotherapy. Each patient underwent HE4 and CA 125 level measurements at the
      time of diagnosis and subsequently as follows: after surgical treatment, after
      the third course of adjuvant chemotherapy, before interval cytoreductive surgery
      and after chemotherapy. The HE4 value was assessed based on the PSF, OS, DFS,
      surgical outcome, two-year survival and platinum sensitivity. RESULTS:
      Preoperative HE4 levels were a predictor of platinum sensitivity (AUC- 0.644; p =
      0.035) and DFS (AUC = 0.637; p = 0.0492). A univariate logistic regression
      analysis showed that serum HE4 significantly correlated with PFS (baseline
      results over median HR = 2.96, p = 0.0009; baseline over 75 percentile HR = 2.44,
      p = 0.0062; normalization after treatment HR = 0.46, p = 0.0125; 50% reduction
      before IDS HR = 0.64, p = 0.0017). In the multivariate analysis, normalization
      after treatment and 50% reduction before IDS significantly influenced the PFS (HR
      = 0.29, p = 0.00008; HR = 0.23, p = 0.0024). The HE4 levels also correlated with
      the OS as follows: values below the median (HR = 1.88, p = 0.0087), normalization
      after chemotherapy (HR = 0.08, p = 0.0003), and 50% reduction before IDS (HR =
      0.39, p = 0.0496). CONCLUSIONS: The significant effect of the normalization of
      the HE4 marker after therapy and 50% reduction of HE4 levels before interval
      cytoreductive surgery on PFS and OS confirmed that HE4 might be an independent
      prognostic factor of treatment response. HE4 measurements performed during first
      line treatment of ovarian cancer may have prognostic significance.

PMID- 29584740
TI  - Panax quinquefolius saponins combined with dual antiplatelet drug therapy
      alleviate gastric mucosal injury and thrombogenesis through the COX/PG pathway in
      a rat model of acute myocardial infarction.
AB  - OBJECTIVES: Previous studies have found that Panax quinquefolius saponins (PQS)
      combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel
      enhances antithrombotic effects while reducing gastric mucosal injury induced by
      DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through
      the COX/PG pathways. METHODS: Acute myocardial infarction (AMI) was induced in
      Wistar rats by ligation of the left anterior descending (LAD) coronary artery,
      and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats
      in the sham group did not undergo artery ligation. They were intragastrically
      treated for 14 days. Myocardial infarct size; myocardial pathology; platelet
      aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6
      keto-PGF1alpha, tissue plasminogen activator (t-PA), and plasminogen activator
      inhibitor (PAI), the TXB2/6-keto-PGF1alpha ratio were measured. The
      ultrastructure of the gastric mucosa was observed by scanning electron
      microscopy. The expression of PGE2 and 6-keto-PGF1alpha in gastric mucosa was
      measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric
      mucosa were assessed using immunohistochemistry. RESULTS: The addition of Panax
      quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly
      decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI
      levels, and the TXB2/6-keto-PGF1alpha ratio, while increasing 6-keto-PGF1alpha
      and t-PA levels and reducing the degree of gastric mucosal injury. Expression of
      PGE2, 6-keto-PGF1alpha, COX-2, and VEGF in the gastric mucosa was upregulated in
      the PQS+DAPT group compared with the standard DAPT group. CONCLUSION: PQS
      increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet
      effects in AMI rats, as well as reducing damage to the gastric mucosa caused by
      DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and
      elevation of 6-keto-PGF1alpha and t-PA levels in blood, and may be associated
      with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue.

PMID- 29584741
TI  - Genome-wide analysis of codon usage bias in four sequenced cotton species.
AB  - Codon usage bias (CUB) is an important evolutionary feature in a genome which
      provides important information for studying organism evolution, gene function and
      exogenous gene expression. The CUB and its shaping factors in the nuclear genomes
      of four sequenced cotton species, G. arboreum (A2), G. raimondii (D5), G.
      hirsutum (AD1) and G. barbadense (AD2) were analyzed in the present study. The
      effective number of codons (ENC) analysis showed the CUB was weak in these four
      species and the four subgenomes of the two tetraploids. Codon composition
      analysis revealed these four species preferred to use pyrimidine-rich codons more
      frequently than purine-rich codons. Correlation analysis indicated that the base
      content at the third position of codons affect the degree of codon preference.
      PR2-bias plot and ENC-plot analyses revealed that the CUB patterns in these
      genomes and subgenomes were influenced by combined effects of translational
      selection, directional mutation and other factors. The translational selection
      (P2) analysis results, together with the non-significant correlation between GC12
      and GC3, further revealed that translational selection played the dominant role
      over mutation pressure in the codon usage bias. Through relative synonymous codon
      usage (RSCU) analysis, we detected 25 high frequency codons preferred to end with
      T or A, and 31 low frequency codons inclined to end with C or G in these four
      species and four subgenomes. Finally, 19 to 26 optimal codons with 19 common ones
      were determined for each species and subgenomes, which preferred to end with A or
      T. We concluded that the codon usage bias was weak and the translation selection
      was the main shaping factor in nuclear genes of these four cotton genomes and
      four subgenomes.

PMID- 29584742
TI  - Patient and physician characteristics affect adherence to screening mammography:
      A population-based cohort study.
AB  - BACKGROUND: Screening mammograms are widely recommended biennially for women
      between the ages of 50 and 74. Despite the benefits of screening mammograms, full
      adherence to recommendations falls below 75% in most developed countries. Many
      studies have identified individual (obesity, smoking, socio-economic status, and
      co-morbid conditions) and primary-care physician parameters (physician age,
      gender, clinic size and cost) that influence adherence, but little data exists
      from large population studies regarding the interaction of these individual
      factors. METHODS: We performed a historical cohort study of 44,318 Israeli women
      age 56-74 using data captured from electronic medical records of a large Israeli
      health maintenance organization. Univariate analysis was used to examine the
      association between each factor and adherence (none, partial or full) with
      screening recommendations between 2008-2014. Multivariate analysis was used to
      examine the significance of these factors in combination, using binary and
      multinomial logistic regression. RESULTS: Among 44,318 women, 42%, 43% and 15%
      were fully, partially and non-adherent to screening recommendations,
      respectively. Factors associated with inferior adherence identified in our
      population included: smoking, obesity, low body weight, low socio-economic
      status, depression, diabetes mellitus and infrequent physician visits, while,
      women with ischemic heart disease, female physicians, physicians between the ages
      of 40 and 60, and medium-sized clinics were associated with higher screening
      rates. Most factors remained significant in the multivariate analysis.
      CONCLUSIONS: Both individual and primary-care physician factors contribute to
      adherence to mammography screening guidelines. Strategies to improve adherence
      and address disparities in mammography utilization will need to address these
      factors.

PMID- 29584743
TI  - Partner notification outcomes after integration of an on-site disease
      intervention specialist at a sexually transmitted disease clinic.
AB  - BACKGROUND: Partner notification services (PNS) are highly effective in reducing
      transmission of sexually transmitted diseases (STDs). We assessed outcomes of PNS
      before and after integration of an on-site disease intervention specialist (DIS)
      at a publicly-funded STD clinic. METHODS: From August 2014 to December 2015,
      patients testing positive for infectious syphilis or gonorrhea at the Rhode
      Island STD Clinic were referred to on-site DIS for partner notification. Data on
      PNS outcomes were reviewed for eight months before integration of DIS at the
      clinic and compared to eight months after. RESULTS: Of the 145 index patients
      referred for PNS during the study period (n = 58 before DIS integration, n = 87
      after), 86% were interviewed. DIS integration resulted in a significantly greater
      proportion of index patients interviewed overall (92% versus 76%, p<0.01), on the
      day of diagnosis (85% versus 61%; p<0.01), and in person at the STD clinic (64%
      versus 11%; p<0.01). However, there was no significant difference in number of
      sexual partners named or treated. CONCLUSIONS: Integrating DIS at a publicly
      funded STD clinic resulted in a greater number of index cases interviewed, a
      greater number interviewed in person, and a greater number interviewed on the day
      of diagnosis. Challenges remain in identifying and engaging partners for
      treatment.

PMID- 29584744
TI  - Availability of patient-centered cancer support services: A statewide survey of
      cancer centers.
AB  - The Institute of Medicine recommended in their landmark report "From Cancer
      Patient to Cancer Survivor: Lost in Transition" that services to meet the needs
      of cancer patients should extend beyond physical health issues to include
      functional and psychosocial consequences of cancer. However, no systems exist in
      the US to support state-level data collection on availability of support services
      for cancer patients. Developing a mechanism to systematically collect these data
      and document service availability is essential for guiding comprehensive cancer
      control planning efforts. This study was carried out to develop a protocol for
      implementing a statewide survey of all Commission on Cancer (CoC) accredited
      cancer centers in South Carolina and to implement the survey to examine
      availability of patient support services within the state. We conducted a cross
      sectional survey of CoC-certified cancer centers in South Carolina. An
      administrator at each center completed a survey on availability of five services:
      1) patient navigation; 2) distress screening; 3) genetic risk assessment and
      counseling, 4) survivorship care planning; and 5) palliative care. Completed
      surveys were received from 16 of 17 eligible centers (94%). Of the 16 centers,
      44% reported providing patient navigation; 31% reported conducting distress
      screening; and 44% reported providing genetic risk assessment and counseling.
      Over 85% of centers reported having an active palliative care program, palliative
      care providers and a hospice program, but fewer had palliative outpatient
      services (27%), palliative inpatient beds (50%) or inpatient consultation teams
      (31%). This was a small, yet systematic survey in one state. This study
      demonstrated a practical method for successfully monitoring statewide
      availability of cancer patient support services, including identifying service
      gaps.

PMID- 29584745
TI  - Derivation of intermediate to silicic magma from the basalt analyzed at the Vega
      2 landing site, Venus.
AB  - Geochemical modeling using the basalt composition analyzed at the Vega 2 landing
      site indicates that intermediate to silicic liquids can be generated by
      fractional crystallization and equilibrium partial melting. Fractional
      crystallization modeling using variable pressures (0.01 GPa to 0.5 GPa) and
      relative oxidation states (FMQ 0 and FMQ -1) of either a wet (H2O = 0.5 wt%) or
      dry (H2O = 0 wt%) parental magma can yield silicic (SiO2 > 60 wt%) compositions
      that are similar to terrestrial ferroan rhyolite. Hydrous (H2O = 0.5 wt%) partial
      melting can yield intermediate (trachyandesite to andesite) to silicic
      (trachydacite) compositions at all pressures but requires relatively high
      temperatures (>= 950 degrees C) to generate the initial melt at intermediate to
      low pressure whereas at high pressure (0.5 GPa) the first melts will be generated
      at much lower temperatures (< 800 degrees C). Anhydrous partial melt modeling
      yielded mafic (basaltic andesite) and alkaline compositions (trachybasalt) but
      the temperature required to produce the first liquid is very high (>= 1130
      degrees C). Consequently, anhydrous partial melting is an unlikely process to
      generate derivative liquids. The modeling results indicate that, under certain
      conditions, the Vega 2 composition can generate silicic liquids that produce
      granitic and rhyolitic rocks. The implication is that silicic igneous rocks may
      form a small but important component of the northeast Aphrodite Terra.

PMID- 29584746
TI  - Communication calls produced by electrical stimulation of four structures in the
      guinea pig brain.
AB  - One of the main central processes affecting the cortical representation of
      conspecific vocalizations is the collateral output from the extended motor system
      for call generation. Before starting to study this interaction we sought to
      compare the characteristics of calls produced by stimulating four different parts
      of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we
      were able to reposition electrodes without distressing the animals. Trains of 100
      electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG),
      hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure
      produced a similar range of calls, but in significantly different proportions.
      Two of the spontaneous calls (chirrup and purr) were never produced by electrical
      stimulation and although we identified versions of chutter, durr and tooth
      chatter, they differed significantly from our natural call templates. However, we
      were routinely able to elicit seven other identifiable calls. All seven calls
      were produced both during the 1.6 s period of stimulation and subsequently in a
      period which could last for more than a minute. A single stimulation site could
      produce four or five different calls, but the amygdala was much less likely to
      produce a scream, whistle or rising whistle than any of the other structures.
      These three high-frequency calls were more likely to be produced by females than
      males. There were also differences in the timing of the call production with the
      amygdala primarily producing calls during the electrical stimulation and the
      hypothalamus mainly producing calls after the electrical stimulation. For all
      four structures a significantly higher stimulation current was required in males
      than females. We conclude that all four structures can be stimulated to produce
      fictive vocalizations that should be useful in studying the relationship between
      the vocal motor system and cortical sensory representation.

PMID- 29584747
TI  - Are narcissists more attracted to people in relationships than to people not in
      relationships?
AB  - Does grandiose narcissism predict greater attraction for others in relationships?
      We examined this question by replicating previous work implicating grandiose
      narcissists as mate poachers (Studies 1 and 2). We then used an experimental
      paradigm (Studies 3 and 4) to assess the extent to which grandiose narcissists
      indicate a greater interest in someone who is already in a relationship compared
      to someone who is single. Results suggest that although grandiose narcissism
      related to reports of more frequent mate poaching attempts, grandiose narcissists
      did not appear to be more interested in taking someone away from an existing
      relationship. Instead, participants took their own relationship status into
      consideration (rather than the relationship status of a target) when evaluating
      their interest in a target for a short-term fling or a long-term relationship.
      Thus, although grandiose narcissists report more frequent mate poaching attempts,
      they do not appear to be more interested in people in relationships compared to
      those who are single.

PMID- 29584748
TI  - Chemical characterization and biological activity in young sesame leaves (Sesamum
      indicum L.) and changes in iridoid and polyphenol content at different growth
      stages.
AB  - Three iridoids (lamalbid (I1), sesamoside (I2) and shanzhiside methyl ester (I3))
      and seven polyphenols (cistanoside F (P1), chlorogenic acid (P2), pedalitin-6-O
      laminaribioside (P3), pedaliin (P4), isoacteoside (P6), pedalitin (P7) and
      martynoside (P8)) were identified in young sesame leaves (Sesamum indicum L.)
      other than the acteoside (P5) reported previously. P3 was a new compound, and I1,
      I3, P2 and P8 were found in a species of Sesamum for the first time. HPLC
      analyses revealed that the compounds I1 (0.29-1.75% of dry leaves), I2 (0.38
      0.87%), I3 (0.04-1.07%), P4 (0.01-2.05%) and P5 (0.13-4.86%) were present
      primarily in young sesame leaves and were found in plants cultivated on different
      farms (plant height, 30-70 cm). Of the identified compounds, P5 and P6 showed
      high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, oxygen radical
      absorbance capacity (ORAC), and in vitro antiglycation activities. Given its
      content, P5 makes a major contribution to the biological activities of young
      sesame leaves. The compounds were examined at six different growth stages of
      plants cultured in a greenhouse to determine the optimum harvest stage and for
      end-use assessment. P5 accumulated in the leaves during growth, and the content
      reached a maximum of 12.9% of dry leaves in the 4th stage (plant height, 74.5+/
      9.7 cm), which is one of the highest percentages reported in plants from nature.

PMID- 29584749
TI  - Effectiveness of integrated care model for type 2 diabetes: A population-based
      study in Reggio Emilia (Italy).
AB  - AIMS: To compare the effectiveness of integrated care with that of the diabetes
      clinic care model in terms of mortality and hospitalisation of type 2 diabetes
      patients with low risk of complications. METHODS: Out of 27234 people with type 2
      diabetes residing in the province of Reggio Emilia on 31/12/2011, 3071 were
      included in this cohort study as eligible for integrated care (i.e., low risk of
      complications) and cared for with the same care model for at least two years.
      These patients were followed up from 2012 to 2016, for all-cause and diabetes
      related mortality and hospital admissions. We performed a Poisson regression
      model, using the proportion of eligible patients included in the integrated care
      model for each general practitioner as an instrumental variable. RESULTS: 1700
      patients were cared for by integrated care and 1371 by diabetes clinics.
      Mortality rate ratios were 0.83 (95%CI 0.60-1.13) and 0.95 (95%CI 0.54-1.70) for
      all-cause and cardiovascular mortality, respectively, and incidence rate ratios
      were 0.90 (95%CI 0.76-1.06) and 0.91 (95%CI 0.69-1.20) for all-cause and
      cardiovascular disease hospitalisation, respectively. CONCLUSION: For low risk
      patients with type 2 diabetes, the integrated care model involving both general
      practitioner and diabetes clinic professionals showed similar mortality and
      hospitalisation as a model with higher use of specialized care in an exclusively
      diabetes clinic setting.

PMID- 29584750
TI  - Unexpected binding behaviors of bacterial Argonautes in human cells cast doubts
      on their use as targetable gene regulators.
AB  - Prokaryotic Argonaute proteins (pAgos) have been proposed as an alternative to
      the CRISPR/Cas9 platform for gene editing. Although Argonaute from
      Natronobacterium gregoryi (NgAgo) was recently shown unable to cleave genomic DNA
      in mammalian cells, the utility of NgAgo or other pAgos as a targetable DNA
      binding platform for epigenetic editing has not been explored. In this report, we
      evaluated the utility of two prokaryotic Argonautes (NgAgo and TtAgo) as DNA
      guided DNA-binding proteins. NgAgo showed no meaningful binding to chromosomal
      targets, while TtAgo displayed seemingly non-specific binding to chromosomal DNA
      even in the absence of guide DNA. The observed lack of DNA-guided targeting and
      unexpected guide-independent genome sampling under the conditions in this study
      provide evidence that these pAgos might be suitable for neither gene nor
      epigenome editing in mammalian cells.

PMID- 29584751
TI  - Accuracy of speckle tracking in the context of stress echocardiography in short
      axis view: An in vitro validation study.
AB  - AIM: This study aimed to test the accuracy of a speckle tracking algorithm to
      assess myocardial deformation in a large range of heart rates and strain
      magnitudes compared to sonomicrometry. METHODS AND RESULTS: Using a tissue
      mimicking phantom with cyclic radial deformation, radial strain derived from
      speckle tracking (RS-SpT) of the upper segment was assessed in short axis view by
      conventional echocardiography (Vivid q, GE) and post-processed with clinical
      software (EchoPAC, GE). RS-SpT was compared with radial strain measured
      simultaneously by sonomicrometers (RS-SN). Radial strain was assessed with
      increasing deformation rates (60 to 160 beats/min) and increasing pulsed volumes
      (50 to 100 ml/beat) to simulate physiological changes occurring during stress
      echocardiography. There was a significant correlation (R2 = 0.978, P <0.001) and
      a close agreement (bias +/- 2SD, 0.39 +/- 1.5%) between RS-SpT and RS-SN. For low
      strain values (<15%), speckle tracking showed a small but significant
      overestimation of radial strain compared to sonomicrometers. Two-way analysis of
      variance did not show any significant effect of the deformation rate. For RS-SpT,
      the feasibility was excellent and the intra- and inter-observer variability were
      low (the intraclass correlation coefficients were 0.96 and 0.97, respectively).
      CONCLUSIONS: Speckle tracking demonstrated a good correlation with sonomicrometry
      for the assessment of radial strain independently of the heart rate and strain
      magnitude in a physiological range of values. Though speckle tracking seems to be
      a reliable and reproducible technique to assess myocardial deformation variations
      during stress echocardiography, further studies are mandated to analyze the
      impact of angulated and artefactual out-of-plane motions and inter-vendor
      variability.

PMID- 29584752
TI  - Use of adjuvant chemotherapy in patients with stage III colon cancer in Puerto
      Rico: A population-based study.
AB  - OBJECTIVE: This study aims to examine factors associated with the use of adjuvant
      chemotherapy and the use of oxaliplatin after curative resection in stage III
      colon cancer patients and assesses the effect of their use in three-year
      survival. METHODS: This retrospective cohort study was conducted using Puerto
      Rico Central Cancer Registry-Health Insurance Linkage Database. The study cohort
      consisted of stage III colon cancer patients with a curative surgery in the
      period 2008-2012. Multivariate logistic regression was used to estimate adjusted
      odds ratios. Kaplan-Meier methods and Cox proportional hazards models were used
      to assess the association between adjuvant chemotherapy and oxaliplatin use and
      overall survival and risk of death, respectively. RESULTS: Overall, 75% of the
      study population received adjuvant chemotherapy during the study period. Factors
      statistically associated with receiving adjuvant chemotherapy within four months
      after resection included being married (adjusted odds ratio [AOR] 1.64; 95% CI
      1.18-2.28; p = 0.003), and being enrolled in Medicare (AOR 1.68; 95% CI: 1.03
      2.75; p = 0.039) or Medicaid and Medicare dual eligible (AOR 1.66; 95% CI: 1.06
      2.60; p = 0.028). However, patients aged >=70 years were less likely to receive
      adjuvant chemotherapy (AOR 0.22; 95%CI 0.14-0.36; p<0.001). DISCUSSION: We
      observed a significant reduction in mortality in adjuvant chemotherapy treated
      patients. Similarly, patients <70 years treated with oxaliplatin had
      significantly lower risk of death than those who did not, although for patients
      >=70 years no statistical significance was achieved. Future studies should assess
      effective interventions to reduce barriers to access guideline-based recommended
      colon cancer treatment.

PMID- 29584753
TI  - Empirical approach to threshold determination for the delineation of built-up
      areas with road network data.
AB  - Various approaches have been proposed to address the delineation of built-up
      areas for a wide range of applications. Recently developed approaches are based
      on the increasing availability of road network data. However, most approaches
      have employed one or more parameters to divide built-up from non-built-up areas.
      Very few studies have discussed how to determine appropriate thresholds for such
      parameters. This study employed an empirical approach for threshold
      determination, and validated that the approach is applicable for the delineation
      of built-up areas using road network data. A series of experiments were designed
      to investigate the most-appropriate thresholds (determined using a similarity
      measure) for multiple parameters of three existing approaches (street blocks,
      grid-based, and kernel density) with regard to different administrative regions
      and cities/towns. The results show that in most cases, the most-appropriate
      thresholds or ranges for different subdivisions are either identical or overlap
      thus validating the use of the most-appropriate thresholds to delineate built-up
      areas for one or multiple small subdivisions and, by inference, for a much larger
      region.

PMID- 29584754
TI  - Long-term delivery of brain-derived neurotrophic factor (BDNF) from nanoporous
      silica nanoparticles improves the survival of spiral ganglion neurons in vitro.
AB  - Sensorineural hearing loss (SNHL) can be overcome by electrical stimulation of
      spiral ganglion neurons (SGNs) via a cochlear implant (CI). Restricted CI
      performance results from the spatial gap between the SGNs and the electrode, but
      the efficacy of CI is also limited by the degeneration of SGNs as one consequence
      of SHNL. In the healthy cochlea, the survival of SGNs is assured by endogenous
      neurotrophic support. Several applications of exogenous neurotrophic supply have
      been shown to reduce SGN degeneration in vitro and in vivo. In the present study,
      nanoporous silica nanoparticles (NPSNPs), with an approximate diameter of <100
      nm, were loaded with the brain-derived neurotrophic factor (BDNF) to test their
      efficacy as long-term delivery system for neurotrophins. The neurotrophic factor
      was released constantly from the NPSNPs over a release period of 80 days when the
      surface of the nanoparticles had been modified with amino groups. Cell culture
      investigations with NIH3T3 fibroblasts attest a good general cytocompatibility of
      the NPSNPs. In vitro experiments with SGNs indicate a significantly higher
      survival rate of SGNs in cell cultures that contained BDNF-loaded nanoparticles
      compared to the control culture with unloaded NPSNPs (p<0.001). Importantly, also
      the amounts of BDNF released up to a time period of 39 days increased the
      survival rate of SGNs. Thus, NPSNPs carrying BDNF are suitable for the treatment
      of inner ear disease and for the protection and the support of SGNs. Their
      nanoscale nature and the fact that a direct contact of the nanoparticles and the
      SGNs is not necessary for neuroprotective effects, should allow for the facile
      preparation of nanocomposites, e.g., with biocompatible polymers, to install
      coatings on implants for the realization of implant-based growth factor delivery
      systems.

PMID- 29584755
TI  - Flexibility evaluation of multiechelon supply chains.
AB  - Multiechelon supply chains are complex logistics systems that require flexibility
      and coordination at a tactical level to cope with environmental uncertainties in
      an efficient and effective manner. To cope with these challenges, mathematical
      programming models are developed to evaluate supply chain flexibility. However,
      under uncertainty, supply chain models become complex and the scope of
      flexibility analysis is generally reduced. This paper presents a unified approach
      that can evaluate the flexibility of a four-echelon supply chain via a robust
      stochastic programming model. The model simultaneously considers the plans of
      multiple business divisions such as marketing, logistics, manufacturing, and
      procurement, whose goals are often conflicting. A numerical example with
      deterministic parameters is presented to introduce the analysis, and then, the
      model stochastic parameters are considered to evaluate flexibility. The results
      of the analysis on supply, manufacturing, and distribution flexibility are
      presented. Tradeoff analysis of demand variability and service levels is also
      carried out. The proposed approach facilitates the adoption of different
      management styles, thus improving supply chain resilience. The model can be
      extended to contexts pertaining to supply chain disruptions; for example, the
      model can be used to explore operation strategies when subtle events disrupt
      supply, manufacturing, or distribution.

PMID- 29584756
TI  - Transcriptional signature associated with early rheumatoid arthritis and healthy
      individuals at high risk to develop the disease.
AB  - BACKGROUND: Little is known regarding the mechanisms underlying the loss of
      tolerance in the early and preclinical stages of autoimmune diseases. The aim of
      this work was to identify the transcriptional profile and signaling pathways
      associated to non-treated early rheumatoid arthritis (RA) and subjects at high
      risk. Several biomarker candidates for early RA are proposed. METHODS: Whole
      blood total RNA was obtained from non-treated early RA patients with <1 year of
      evolution as well as from healthy first-degree relatives of patients with RA
      (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels
      against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized
      and hybridized to high-density microarrays. Data was analyzed in Genespring
      Software and functional categories were assigned to a specific transcriptome
      identified in subjects with RA and FDR ACCP positive. Specific signaling pathways
      for genes associated to RA were identified. Gene expression was evaluated by
      qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these
      genes as biomarkers. RESULTS: A characteristic transcriptome of 551 induced genes
      and 4,402 repressed genes were identified in early RA patients. Bioinformatics
      analysis of the data identified a specific transcriptome in RA patients.
      Moreover, some overlapped transcriptional profiles between patients with RA and
      ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from
      the preclinical stages up to progression to an early RA state. A total of 203
      pathways have up-regulated genes that are shared between RA and ACCP+. Some of
      these genes show potential to be used as progression biomarkers for early RA with
      area under the curve of ROC > 0.92. These genes come from several functional
      categories associated to inflammation, Wnt signaling and type I interferon
      pathways. CONCLUSION: The presence of a specific transcriptome in whole blood of
      RA patients suggests the activation of a specific inflammatory transcriptional
      signature in early RA development. The set of overexpressed genes in early RA
      patients that are shared with ACCP+ subjects but not with ACCP- subjects, can
      represent a transcriptional signature involved with the transition of a
      preclinical to a clinical RA stage. Some of these particular up-regulated and
      down-regulated genes are related to inflammatory processes and could be
      considered as biomarker candidates for disease progression in subjects at risk to
      develop RA.

PMID- 29584757
TI  - Transcriptome analysis of genetically matched human induced pluripotent stem
      cells disomic or trisomic for chromosome 21.
AB  - Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential
      to alter expression of genes on chromosome 21, as well as other locations
      throughout the genome. These transcriptome changes are likely to underlie the
      Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in
      depth analysis of transcriptome changes resulting from trisomy of chromosome 21,
      using induced pluripotent stem cells (iPSCs) derived from a single individual
      with Down syndrome. These cells were originally derived by Li et al, who
      genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of
      disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell
      pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In
      addition to characterization of gene expression levels, we have also investigated
      patterns of RNA adenosine-to-inosine editing, alternative splicing, and
      repetitive element expression, aspects of the transcriptome that have not been
      significantly characterized in the context of Down syndrome. We identified
      significant changes in transcript accumulation associated with chromosome 21
      trisomy, as well as changes in alternative splicing and repetitive element
      transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher
      levels of neuronal transcripts than control disomic iPSCs, and readily
      differentiated into cortical neurons, in contrast to another reported study.
      Comparison of our transcriptome data with similar studies of trisomic iPSCs
      suggests that trisomy of chromosome 21 may not intrinsically limit neuronal
      differentiation, but instead may interfere with the maintenance of pluripotency.

PMID- 29584758
TI  - Experimental study of isolas in nonlinear systems featuring modal interactions.
AB  - The objective of the present paper is to provide experimental evidence of
      isolated resonances in the frequency response of nonlinear mechanical systems.
      More specifically, this work explores the presence of isolas, which are periodic
      solutions detached from the main frequency response, in the case of a nonlinear
      set-up consisting of two masses sliding on a horizontal guide. A careful
      experimental investigation of isolas is carried out using responses to swept-sine
      and stepped-sine excitations. The experimental findings are validated with
      advanced numerical simulations combining nonlinear modal analysis and bifurcation
      monitoring. In particular, the interactions between two nonlinear normal modes
      are shown to be responsible for the creation of the isolas.

PMID- 29584759
TI  - Anti-inflammatory cytokine and angiogenic factors levels in vitreous samples of
      diabetic retinopathy patients.
AB  - Evaluation of cytokines in patients with diabetic retinopathy (DR) is important
      for the identification of future additive or alternative treatment options.
      Therefore, vitreous samples were obtained from patients with DR and patients with
      macular hole or macular pucker (control group) during 23-gauge-vitrectomy (n =
      17/group). The levels of three pro-inflammatory (IL-1beta, IL-6, IFN-gamma) and
      pleiotropic cytokines (IL-2, IL-4, IL-13) as well as VEGF, VEGF-A, and PGF were
      measured using an enzyme linked immunosorbent assay (ELISA). IL-1beta (p = 0.02)
      and IFN-gamma (p = 0.04), two of the three tested pro-inflammatory cytokines,
      were elevated in the DR patients, while IL-6 (p = 0.51) level was comparable in
      both groups. Moreover, in DR samples, a trend towards an IL-13 down-regulation (p
      = 0.36) was observable. The IL-2 (p = 0.62) and IL-4 (p = 0.78) levels were
      comparable in both groups. All analyzed angiogenetic factors were up-regulated in
      DR patients (VEGF: p<0.001; VEGF-A: p = 0.002; PGF: p<0.001). The up-regulation
      of angiogenetic factors underline their importance in DR development. However,
      the interaction of the other cytokines showed an interesting pattern. Pro
      inflammatory cytokines were also up-regulated, which could be evidence for
      inflammation processes in the diabetic retina. Furthermore, it seems that a
      counter response of immunomodulatory cytokines is in an initial process, but not
      strong enough to regulate the processes. Therefore, to support these anti
      inflammatory mechanisms might be additive treatment option in the future.

PMID- 29584760
TI  - The influence of transcript assembly on the proteogenomics discovery of
      microproteins.
AB  - Proteogenomics methods have identified many non-annotated protein-coding genes in
      the human genome. Many of the newly discovered protein-coding genes encode
      peptides and small proteins, referred to collectively as microproteins.
      Microproteins are produced through ribosome translation of small open reading
      frames (smORFs). The discovery of many smORFs reveals a blind spot in traditional
      gene-finding algorithms for these genes. Biological studies have found roles for
      microproteins in cell biology and physiology, and the potential that there exists
      additional bioactive microproteins drives the interest in detection and discovery
      of these molecules. A key step in any proteogenomics workflow is the assembly of
      RNA-Seq data into likely mRNA transcripts that are then used to create a
      searchable protein database. Here we demonstrate that specific features of the
      assembled transcriptome impact microprotein detection by shotgun proteomics. By
      tailoring transcript assembly for downstream mass spectrometry searching, we show
      that we can detect more than double the number of high-quality microprotein
      candidates and introduce a novel open-source mRNA assembler for proteogenomics
      (MAPS) that incorporates all of these features. By integrating our specialized
      assembler, MAPS, and a popular generalized assembler into our proteogenomics
      pipeline, we detect 45 novel human microproteins from a high quality
      proteogenomics dataset of a human cell line. We then characterize the features of
      the novel microproteins, identifying two classes of microproteins. Our work
      highlights the importance of specialized transcriptome assembly upstream of
      proteomics validation when searching for short and potentially rare and poorly
      conserved proteins.

PMID- 29584761
TI  - The first mitochondrial genomes for Pyralinae (Pyralidae) and Glaphyriinae
      (Crambidae), with phylogenetic implications of Pyraloidea.
AB  - In the present study, we report five complete and one nearly complete
      mitochondrial genomes of the Pyraloidea including the first representatives from
      the Pyralinae (Pyralidae) and Glaphyriinae (Crambidae). We also conduct a
      comparative analysis of mitogenomic features of this group. Our results show that
      Pyraloidea mitogenomes evolved under a common trend found in lepidopteran
      mitogenomes and share several typical genomic characters. The extra conserved
      blocks are identified in the Pyraloidea control region, and diverse missing
      codons formed another unique trait within Pyraloidea mitogenome. Furthermore, we
      reconstruct the mitogenomic phylogeny of Pyraloidea and confirm the phylogenetic
      position of Pyralinae and Glaphyriinae within the Pyraloidea using BI and ML
      method based on multiple mitochondrial datasets.

PMID- 29584762
TI  - Generational changes in multiple sclerosis phenotype in North African immigrants
      in France: A population-based observational study.
AB  - BACKGROUND: The incidence of multiple sclerosis (MS) changes from generation to
      generation in ethnically different immigrants compared with native-born people.
      We aimed to determine whether there are generational changes in MS phenotypes
      among North African immigrants in France. METHODS: Cohort study with data from a
      population-based MS registry to compare the clinical characteristics of 80 first
      (NAG1) and 167 second (NAG2) generation North Africans with MS living in France
      with 5200 native-born Europeans. Adjusted Cox models were used to test the
      association between scores of 3 and 6 on the expanded disability status scale
      (EDSS) and the "origin/generation" variable. RESULTS: Cox models for EDSS scores
      3 and 6 showed a higher risk of score 3 (hazard ratio = 1.738, 95% confidence
      interval 1.237 to 2.444; P = .002) and 6 (hazard ratio = 2.372, 95% confidence
      interval 1.626 to 3.462; P<.0001) for NAG1 than Europeans. Being NAG2 was not
      significantly associated with higher hazards of scores 3 and 6. CONCLUSIONS: We
      found two different phenotypes among NAG1 and NAG2 MS patients in France. NAG1,
      but not NAG2, have a higher risk of disability than Europeans. This raises the
      question of environmental factors in MS expression, and advocates appropriate
      patient management according to generation in immigrants.

PMID- 29584763
TI  - Child injuries in Ethiopia: A review of the current situation with projections.
AB  - BACKGROUND: Heavy burden of child injuries and lack of policy response in
      Ethiopia call for an improved understanding of the situation and development of
      action plans from multiple governmental agencies and stakeholders. METHODS: A
      consortium of international and Ethiopian researchers and stakeholders used
      extensive literature review and mixed analytical methods to estimate and project
      the burden of fatal and non-fatal child unintentional injuries in Ethiopia from
      2015 to 2030. Estimates were derived for children aged 0-14 years. Data sources
      include a longitudinal study conducted by the Central Statistics Agency of
      Ethiopia and the World Bank as well as model-based estimates from World Health
      Organization 2017 and Global Burden of Disease 2016 project. RESULTS: Injuries
      caused about 25 thousand deaths among 0-14-year olds in Ethiopia in 2015. The
      leading cause of fatal child unintentional injuries in Ethiopia was road-traffic
      injuries, followed by fire, heat and hot substances and drowning. The death rate
      due to injuries among 0-14 years olds was about 50 percent higher in males than
      females. Rural children were exposed to a greater risk of injury than their urban
      peers. The longitudinal survey suggests that the incidence rate of child injuries
      increased during the period 2011-2014. The annual mortality caused by injuries is
      projected to increase from 10,697 in 2015 to 11,279 in 2020 and 11,989 in 2030
      among children under 5 years, an increase of 12 percentage points in 15 years.
      The number of deaths among 0-14-year olds will be 26,463, 27,807, and 30,364
      respectively in 2015, 2020, and 2030. CONCLUSIONS: As the first multisectoral
      collaboration on child injuries in Ethiopia, this study identified gaps in
      understanding of the burden of child injuries in Ethiopia. In consultation with
      Ethiopian government and other stakeholders, we propose starting an injury
      surveillance system at health clinics and hospitals and building an intervention
      package based on existing platforms.

PMID- 29584764
TI  - Effects of a combination of plant bioactive lipid compounds and biotin compared
      with monensin on body condition, energy metabolism and milk performance in
      transition dairy cows.
AB  - The aim of this study was to test whether a combination of plant bioactive lipid
      compounds (also termed 'essential oils') and biotin (PBLC+B) could decrease the
      mobilization of body reserves and ketosis incidence in postpartum dairy cows. We
      compared non-supplemented control (CON) cows with cows receiving monensin (MON)
      as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day
      (d) -21 before calving until calving (Phase 1) and further until d 37 after
      calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase
      3). The PBLC+B cows had higher body weight and higher back fat thickness than CON
      cows and lesser body weight change than MON and CON cows in Phase 3. Body
      condition score was not different among groups. Milk protein concentration tended
      to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat
      concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with
      significantly higher values in PBLC+B vs. MON cows on the second herd test day.
      Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in
      Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence
      of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows,
      respectively, with lower mean beta-hydroxybutyrate values in MON than in PBLC+B
      cows in Phase 1 prepartum. The serum triglyceride concentration was higher in
      PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea,
      non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate
      transaminase and gamma-glutamyltranspeptidase but not glutamate dehydrogenase
      activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We
      conclude that PBLC+B prevent body weight loss after parturition and are
      associated with similar ketosis incidence and partly higher yields of energy
      corrected milk compared to MON supplementation of dairy cows.

PMID- 29584766
TI  - Correction: Tph2-/- female mice restore socio-sexual recognition through
      upregulating ERalpha and OTR genes in the amygdala.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193395.].

PMID- 29584765
TI  - Dissimilar flexibility of alpha and beta subunits of human adult hemoglobin
      influences the protein dynamics and its alteration induced by allosteric
      effectors.
AB  - The general question by what mechanism an "effector" molecule and the hemes of
      hemoglobin interact over widely separated intramolecular distances to change the
      oxygen affinity has been extensively investigated, and still has remained of
      central interest. In the present work we were interested in clarifying the
      general role of the protein matrix and its dynamics in the regulation of human
      adult hemoglobin (HbA). We used a spectroscopy approach that yields the
      compressibility (kappa) of the protein matrix around the hemes of the subunits in
      HbA and studied how the binding of heterotropic allosteric effectors modify this
      parameter. kappa is directly related to the variance of volume fluctuation,
      therefore it characterizes the molecular dynamics of the protein structure. For
      the experiments the heme groups either in the alpha or in the beta subunits of
      HbA were replaced by fluorescent Zn-protoporphyrinIX, and series of fluorescence
      line narrowed spectra were measured at varied pressures. The evaluation of the
      spectra yielded the compressibility that showed significant dynamic asymmetry
      between the subunits: kappa of the alpha subunit was 0.17+/-0.05/GPa, while for
      the beta subunit it was much higher, 0.36+/-0.07/GPa. The heterotropic effectors,
      chloride ions, inositol hexaphosphate and bezafibrate did not cause significant
      changes in kappa of the alpha subunits, while in the beta subunits the effectors
      lead to a significant reduction down to 0.15+/-0.04/GPa. We relate our results to
      structural data, to results of recent functional studies and to those of
      molecular dynamics simulations, and find good agreements. The observed asymmetry
      in the flexibility suggests a distinct role of the subunits in the regulation of
      Hb that results in the observed changes of the oxygen binding capability.

PMID- 29584768
TI  - Global nutrition 1990-2015: A shrinking hungry, and expanding fat world.
AB  - OBJECTIVES: Following its publication in 2008, the Global Nutritional Index (GNI)
      which captures the triple burden of malnutrition, has been updated to assess the
      overall nutritional status and nutritional trends of countries, regions and the
      world, including both under-nutrition and over-nutrition. METHODS: The GNI was
      modeled on the Human Development Index, using geometric means of three normalized
      indicators: protein-energy malnutrition (PEM, measured by Disability-Adjusted
      Life Years (DALYs) from PEM), micronutrient deficiency (MID, measured by DALYs
      from MID), and penalizing obesity (percent female obesity). GNI (range 0-1) was
      calculated from 1990-2015 for 186 countries, in seven World Bank income and WHO
      region groupings. RESULTS: World GNI increased from 0.433 to 0.473 as decreased
      deficits overcompensated for the rise in obesity. GNI for African low- and middle
      income countries (LMIC) (median 0.301 to 0.392) and South-East Asian LMIC (0.456
      to 0.564) improved significantly (P<0.001), while for high-income countries
      (0.657 to 0.611) worsened significantly (P<0.001). GNI for American LMIC (0.459
      to 0.457), European LMIC (0.571 to 0.575), Eastern Mediterranean LMIC (0.484 to
      0.483) and Western Pacific LMIC (0.433 to 0.494) were unchanged. The
      disaggregation of the GNI showed that in nearly all the seven country groups
      there was a significant decrease in both PEM and MID (all P<0.01) (except in HIC
      where only PEM dropped), and a significant increase in obesity (all P<0.001).
      CONCLUSION: These trends are the result of the reciprocal changes between
      decreased under-nutrition and increased over-nutrition, which has become a major
      cause of malnutrition worldwide. We suggest, therefore, that future Sustainable
      Development Goals should include alongside "zero hunger"-"reduce obesity".

PMID- 29584767
TI  - 4000 years of human dietary evolution in central Germany, from the first farmers
      to the first elites.
AB  - Investigation of human diet during the Neolithic has often been limited to a few
      archaeological cultures or single sites. In order to provide insight into the
      development of human food consumption and husbandry strategies, our study
      explores bone collagen carbon and nitrogen isotope data from 466 human and 105
      faunal individuals from 26 sites in central Germany. It is the most extensive
      data set to date from an enclosed geographic microregion, covering 4,000 years of
      agricultural history from the Early Neolithic to the Early Bronze Age. The animal
      data show that a variety of pastures and dietary resources were explored, but
      that these changed remarkably little over time. In the human delta15N however we
      found a significant increase with time across the different archaeological
      cultures. This trend could be observed in all time periods and archaeological
      cultures (Bell Beaker phenomenon excluded), even on continuously populated sites.
      Since there was no such trend in faunal isotope values, we were able largely to
      exclude manuring as the cause of this effect. Based on the rich interdisciplinary
      data from this region and archaeological period we can argue that meat
      consumption increased with the increasing duration of farming subsistence. In
      delta13C, we could not observe any clear increasing or decreasing trends during
      the archaeological time periods, either for humans or for animals, which would
      have suggested significant changes in the environment and landscape use. We
      discovered sex-related dietary differences, with males of all archaeological
      periods having higher delta15N values than females, and an age-related increasing
      consumption of animal protein. An initial decrease of delta15N-values at the age
      of 1-2 years reveals partial weaning, while complete weaning took place at the
      age of 3-4 years.

PMID- 29584769
TI  - Development of a repeat-exposure penile SHIV infection model in macaques to
      evaluate biomedical preventions against HIV.
AB  - Penile acquisition of HIV infection contributes substantially to the global
      epidemic. Our goal was to establish a preclinical macaque model of penile HIV
      infection for evaluating the efficacy of new HIV prevention modalities. Rhesus
      macaques were challenged once or twice weekly with consistent doses of
      SHIVsf162P3 (a chimeric simian-human immunodeficiency virus containing HIV env)
      ranging from 4-600 TCID50 (50% tissue culture infective dose), via two penile
      routes, until systemic SHIV infection was confirmed. One route exposed the inner
      foreskin, glans and urethral os to virus following deposition into the prepuce
      (foreskin) pouch. The second route introduced the virus non-traumatically into
      the distal urethra only. Single-route challenges resulted in dose-dependent rates
      of SHIV acquisition informing selection of optimal SHIV dosing. Concurrent SHIV
      challenges via the prepuce pouch (200 TCID50) and urethra (16 TCID50) resulted in
      infection of 100% (10/10) animals following a median of 2.5 virus exposures
      (range, 1-12). We describe the first rhesus macaque repeat-exposure SHIV
      challenge model of penile HIV acquisition. Utilization of the model should
      further our understanding of penile HIV infection and facilitate the development
      of new HIV prevention strategies for men.

PMID- 29584770
TI  - Visualizing the Bayesian 2-test case: The effect of tree diagrams on medical
      decision making.
AB  - In medicine, diagnoses based on medical test results are probabilistic by nature.
      Unfortunately, cognitive illusions regarding the statistical meaning of test
      results are well documented among patients, medical students, and even
      physicians. There are two effective strategies that can foster insight into what
      is known as Bayesian reasoning situations: (1) translating the statistical
      information on the prevalence of a disease and the sensitivity and the false
      alarm rate of a specific test for that disease from probabilities into natural
      frequencies, and (2) illustrating the statistical information with tree diagrams,
      for instance, or with other pictorial representation. So far, such strategies
      have only been empirically tested in combination for "1-test cases", where one
      binary hypothesis ("disease" vs. "no disease") has to be diagnosed based on one
      binary test result ("positive" vs. "negative"). However, in reality, often more
      than one medical test is conducted to derive a diagnosis. In two studies, we
      examined a total of 388 medical students from the University of Regensburg
      (Germany) with medical "2-test scenarios". Each student had to work on two
      problems: diagnosing breast cancer with mammography and sonography test results,
      and diagnosing HIV infection with the ELISA and Western Blot tests. In Study 1 (N
      = 190 participants), we systematically varied the presentation of statistical
      information ("only textual information" vs. "only tree diagram" vs. "text and
      tree diagram in combination"), whereas in Study 2 (N = 198 participants), we
      varied the kinds of tree diagrams ("complete tree" vs. "highlighted tree" vs.
      "pruned tree"). All versions were implemented in probability format (including
      probability trees) and in natural frequency format (including frequency trees).
      We found that natural frequency trees, especially when the question-related
      branches were highlighted, improved performance, but that none of the
      corresponding probabilistic visualizations did.

PMID- 29584771
TI  - Interaction of microtubule depolymerizing agent indanocine with different human
      alphabeta tubulin isotypes.
AB  - Tubulin isotypes are known to regulate the stability and dynamics of
      microtubules, and are also involved in the development of resistance against
      microtubule-targeted cancer drugs. Indanocine, a potent microtubule
      depolymerizing agent, is highly active against multidrug-resistant (MDR) cancer
      cells without affecting normal cells. It is known to disrupt microtubule dynamics
      in cells and induce apoptotic cell death. Indanocine is reported to bind to
      tubulin at the colchicine site i.e. at the interface of alphabeta tubulin
      heterodimer. However, it's precise binding mode, involved molecular interactions
      and the binding affinities with different alphabeta-tubulin isotypes present in
      MDR cells are not well understood. Here, the binding affinities of human
      alphabeta-tubulin isotypes with indanocine were examined, employing the molecular
      modeling approach i.e. docking, molecular dynamics simulation and binding energy
      calculations. Multiple sequence analysis suggests that the amino acid sequences
      are different in the indanocine binding pockets of betaI, betaIIa, betaIII and
      betaVI isotypes. However, such differences are not observed in the amino acid
      sequences of betaIVa, betaIVb, and betaV tubulin isotypes at indanocine binding
      pockets. Docking and molecular dynamics simulation results show that indanocine
      prefers the interface binding pocket of alphabetaIIa, alphabetaIII, alphabetaIVb,
      alphabetaV, and alphabetaVI tubulin isotypes; whereas it is expelled from the
      interface binding pocket of alphabetaIVa and alphabetaI-tubulin isotypes.
      Further, binding free energy calculations show that alphabetaVI has the highest
      binding affinity and alphabetaI has the lowest binding affinity for indanocine
      among all beta-tubulin isotypes. The binding free energy decreases in the order
      of alphabetaVI > alphabetaIVb > alphabetaIIa > alphabetaIII > alphabetaV >
      alphabetaIVa > alphabetaI. Thus, our study provides a significant understanding
      of involved molecular interactions of indanocine with tubulin isotypes, which may
      help to design potent indanocine analogues for specific tubulin isotypes in MDR
      cells in future.

PMID- 29584772
TI  - Modelling of strategies for genetic control of scrapie in sheep: The importance
      of population structure.
AB  - Scrapie is a transmissible spongiform encephalopathy in sheep and an example of a
      disease that may be controlled through breeding for disease resistance. Member
      states of the European Union have introduced strategies for breeding against
      scrapie based on the selection of genetically resistant breeding rams. An
      ambitious strategy adopted in The Netherlands consisted of selecting resistant
      rams for breeding throughout both breeding and production sectors. Mathematical
      modelling of the effect of a breeding program on the spreading capacity of
      scrapie in a national flock is needed for making assessments on how long a
      breeding strategy needs to be maintained to achieve disease control. Here we
      describe such a model applied to the Dutch situation, with the use of data on the
      genetic content of the Dutch sheep population as well as on scrapie occurrence in
      this population. We show that the time needed for obtaining scrapie control
      depends crucially on two parameters measuring sheep population structure: the
      between-flock heterogeneity in genotype frequencies, and the heterogeneity of
      mixing (contact rates) between sheep flocks. Estimating the first parameter from
      Dutch genetic survey data and assuming scenario values for the second one,
      enables model prediction of the time needed to achieve scrapie control in The
      Netherlands.

PMID- 29584773
TI  - "I am not telling. The mobile is telling": Factors influencing the outcomes of a
      community health worker mHealth intervention in India.
AB  - INTRODUCTION: Improving maternal health outcomes remains a priority in Low and
      Middle Income Countries. With the rapid proliferation of mobile health
      technologies, there is an increased interest in understanding how these
      technologies can effectively improve maternal health outcomes particularly
      maternal health seeking knowledge and behaviors. However, few studies present
      clear explanations of the program developers' rationale (theory of change) and
      contextual factors that could influence program outcomes. This mixed-methods
      study assesses Mobile for Mothers, a community health workers (CHW) utilized
      maternal mHealth intervention. We present the program developers' rationale and
      utilize it as a framework to guide our study that aimed to identify intervention
      related and contextual factors, which influence the observed outcomes of a CHW,
      utilized mHealth intervention. MATERIALS AND METHODS: Quantitative methods (a
      questionnaire with 740 women who received the intervention and survey of 57 CHWs
      who utilized the intervention) and qualitative methods (12 interviews and 4 group
      discussions with CHWs and 20 interviews and 5 group discussions with pregnant and
      lactating women and 15 interviews and 2 group discussions with men) were
      conducted. These were used to understand how the mHealth intervention was
      implemented and to gain insight into contextual factors that potentially
      influenced the observed intervention outcomes. RESULTS: Results were grouped
      following three categories: (1) perceptions and experiences of CHWs utilizing the
      mHealth technology; (2) CHW-related outcomes; and (3) contextual factors that
      influence maternal health-seeking behavior. The overall response of CHWs and
      community members to the intervention was positive. However, contextual factors
      like the relationship between the CHWs and their respective communities, the
      pregnant women's decision-making power and lack of access due to financial
      influenced the observed outcomes. CONCLUSION: Mobile health applications are
      promising interventions for improving the performance of CHWs and health-seeking
      behavior of pregnant women. However, the contextual factors play a crucial role
      in intervention outcomes and need to be explicated by program developers during
      intervention design and implementation.

PMID- 29584774
TI  - Changes in trunk posture and muscle responses in standing during pregnancy and
      postpartum.
AB  - The aim of this study was to analyze the position of the lumbopelvic region and
      the muscle activation of erector spinae and biceps femoris muscles in a group of
      pregnant women in the third trimester. The hypothesis was that pregnancy-related
      biomechanical and morphological changes modify the position of the lumbopelvic
      region and the activation of extensor muscles. The position of the lumbar spine
      and pelvis in the sagittal plane, and the EMG activity of the erector spinae and
      biceps femoris muscles, were recorded during standing in 34 nulliparous and 34
      pregnant women in the third trimester, and also two months after birth in the
      group of pregnant women. No significant differences in the position of the lumbar
      spine or pelvis between the group of pregnant women and nulliparous or postpartum
      were observed. A significant increase was observed in the EMG activity of the
      erector spinae (4.6% vs 2.4% and 2.1% in the nulliparous group and postpartum
      respectively) and the biceps femoris (3.4% vs 1.2% and 1.4%) in pregnant women
      compared to the other two groups (p <0.01). We conclude that pregnant women in
      the third trimester show no alterations in lumbopelvic position compared to
      nulliparous and postpartum women. However, there is an increase of the EMG
      activity of the trunk extensors. These results indicate that the extensor muscles
      of the trunk show, in static positions, adaptive responses to the increase of
      anterior loads during pregnancy.

PMID- 29584775
TI  - A zebrafish model for ocular tuberculosis.
AB  - Ocular tuberculosis (TB) commonly causes severe inflammation and vision loss in
      TB-endemic countries. The mechanism by which tuberculous infection becomes
      established in the eye is poorly understood. We have developed the zebrafish
      larva infected with Mycobacterium marinum as a model to study the early
      pathogenesis of ocular TB. We find that hematogenous bacterial seeding of the eye
      occurs despite a functional blood retinal barrier. Prototypical early granulomas
      form in response to bacteria in the eye. These granulomas involve the retinal
      vasculature and retinal pigment epithelium-choroid complex which are
      characteristic locations for human ocular TB. We find that peripheral blood
      monocytes are recruited to the nascent ocular granuloma further suggesting that
      the immune privileged nature of the eye is breached by this inflammatory focus.

PMID- 29584776
TI  - Retraction: rs10499194 polymorphism in the tumor necrosis factor-alpha inducible
      protein 3 (TNFAIP3) gene is associated with type-1 autoimmune hepatitis risk in
      Chinese Han population.

PMID- 29584777
TI  - Aqueous two-phase system to isolate extracellular vesicles from urine for
      prostate cancer diagnosis.
AB  - Analyzing extracellular vesicles (EVs) is an attractive approach to diagnosis of
      prostate diagnosis. However, existing methods of EVs isolation have low
      efficiency, purity, and long process time, and therefore have low diagnostic
      ability. To solve these the problems, a two-phase system is adapted to isolate
      EVs from a patient's urine. Urine from 20 prostate cancer (PCA) patients and 10
      benign prostate hyperplasia patients was used to quantify the EVs-isolation
      ability of an aqueous two-phase system (ATPS) and to compare the diagnostic
      ability of ATPS with that of the conventional diagnosis method. An optimized ATPS
      isolates EVs with ~100% efficiency within ~30 min, with 14 times as high as
      achieved by ultracentrifugation. Afterward, PCR and ELISA are used to detect EVs
      derived from PCA cells in urine. The results demonstrate that diagnostic ability
      based on ATPS is better than other conventional diagnostic methods. ATPS can
      obtain a high quality and quantity of EVs from patients' urine. EVs contain
      cancer-related protein and genes, so these abundant sources enable diagnosis with
      high specificity and sensitivity. Therefore, ATPS is a useful tool to increase
      the specificity and sensitivity of diagnosis.

PMID- 29584780
TI  - Relating antennal sensilla diversity and possible species behaviour in the
      planthopper pest Lycorma delicatula (Hemiptera: Fulgoromorpha: Fulgoridae).
AB  - Antennal sensory units in nymphs and adults of the spotted Lanternfly, Lycorma
      delicatula (White) (Hemiptera: Fulgoromorpha: Fulgoridae), an economically
      important plant pest, are studied with scanning electron microscopy. Sensilla
      trichodea / chaetica type recognition is based on their external morphology and
      ratio of their size to diameter. The flagellum Bourgoin's organ is a complex
      sensory unit with 2-3 internal sensilla coeloconica. During nymphal stages, the
      sensory surface available for a chemoreceptive function particularly increases
      with the number and size of sensilla placodea on the antennal pedicel. From first
      to fourth instar and to adult males and females, plate organ sensory surface is
      estimated to increase respectively by 33x, 68x and 125x (= 2.72 mm2 and 5.02 mm2
      respectively for males and females). The most important increase (5x) occurs
      between second and third instar. In parallel, a distinctive pair of plate organs
      on the flagellum decreases in size from first to third instar, and disappears.
      Sexual dimorphism occurs in sensilla placodea in adults. Diversity, disparity and
      evolution of nymphal sensilla, and their sexual dimorphism in adults are
      discussed in the context of the species and planthopper behaviour.

PMID- 29584778
TI  - The enzymatic de-epithelialization technique determines denuded amniotic membrane
      integrity and viability of harvested epithelial cells.
AB  - The human amniotic membrane (HAM) is widely used for its wound healing effect in
      clinical practice, as a feeder for the cell cultivation, or a source of cells to
      be used in cell therapy. The aim of this study was to find effective and safe
      enzymatic HAM de-epithelialization method leading to harvesting of both denuded
      undamaged HAM and viable human amniotic epithelial cells (hAECs). The efficiency
      of de-epithelialization using TrypLE Express, trypsin/ ethylenediaminetetraacetic
      (EDTA), and thermolysin was monitored by hematoxylin and eosin staining and by
      the measurement of DNA concentration. The cell viability was determined by trypan
      blue staining. Scanning electron microscopy and immunodetection of collagen type
      IV and laminin alpha5 chain were used to check the basement membrane integrity.
      De-epithelialized hAECs were cultured and their stemness properties and
      proliferation potential was assessed after each passage. The HAM was successfully
      de-epithelialized using all three types of reagents, but morphological changes in
      basement membrane and stroma were observed after the thermolysin application.
      About 60% of cells remained viable using trypsin/EDTA, approximately 6% using
      TrypLE Express, and all cells were lethally damaged after thermolysin
      application. The hAECs isolated using trypsin/EDTA were successfully cultured up
      to the 5th passage with increasing proliferation potential and decreased stem
      cell markers expression (NANOG, SOX2) in prolonged cell culture. Trypsin/EDTA
      technique was the most efficient for obtaining both undamaged denuded HAM and
      viable hAECs for consequent culture.

PMID- 29584779
TI  - Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents
      development of atherosclerosis in high-fat diet-fed apoE-deficient mice via
      ameliorating hyperlipidemia, pro-inflammatory mediators and oxidative responses.
AB  - Pantoea agglomerans (P. agglomerans) is a Gram-negative bacterium that grows
      symbiotically with various edible plants, and the oral or sublingual
      administration of lipopolysaccharide derived from P. agglomerans (LPSp) have been
      suggested to contribute to prevention of immune-related diseases. Our previous
      study indicated that orally administered LPSp was shown to exhibit an LDL
      lowering effect in hyperlipidemic volunteers; however, a preventive effect of
      LPSp on atherosclerosis is unclear. The present study attempted to evaluate the
      anti-atherosclerotic effect by LPSp in a mouse model of high-fat diet (HFD)
      induced atherosclerosis. For 16 weeks, apoE-deficient mice were fed an HFD and
      received drinking water containing LPSp (0.3 or 1 mg/kg body weight/day). The
      results showed that the orally administered LPSp decreased body weight. A
      significant reduction in atherosclerotic plaque deposition was observed even with
      the lower dose of LPSp. The biochemical analyses showed that LPSp markedly
      improved glucose tolerance and reduced plasma LDL and oxidized LDL levels. In
      addition, LPSp significantly reduced the production of pro-inflammatory mediators
      including MCP-1 (in the plasma), TNF-alpha and IL-6 (in the colon), and decreased
      the oxidative burst activities in the peripheral blood sample. Taken together,
      these results suggest the possibility that oral administration of LPSp can
      effectively ameliorate HFD-induced hyperlipidemia and inflammatory/oxidative
      responses to prevent atherosclerosis and related metabolic disorders.

PMID- 29584781
TI  - Working memory, age and education: A lifespan fMRI study.
AB  - Ageing is associated with grey matter atrophy and changes in task-related neural
      activations. This study investigated the effects of age and education on neural
      activation during a spatial working memory task in 189 participants aged between
      20-80 years old, whilst controlling for grey matter density. Age was related to
      linear decreases in neural activation in task activated areas, and this effect
      was no longer significant when adjusting for education or accuracy. Age was also
      related to cubic increases in neural activation in non-task related areas, such
      as the temporal gyrus, cuneus and cerebellum when adjusting for accuracy and
      education. These findings support previous lifespan datasets indicating linear
      age-related decreases in task activation, but non-linear increases in non-task
      related areas during episodic memory tasks. The findings also support past
      studies indicating education offers a form of cognitive reserve through providing
      a form of neural compensation and highlights the need to consider education in
      ageing studies.

PMID- 29584782
TI  - Genomic diversity of Taylorella equigenitalis introduced into the United States
      from 1978 to 2012.
AB  - Contagious equine metritis is a disease of worldwide concern in equids. The
      United States is considered to be free of the disease although sporadic outbreaks
      have occurred over the last few decades that were thought to be associated with
      the importation of horses. The objective of this study was to create finished,
      reference quality genomes that characterize the diversity of Taylorella
      equigenitalis isolates introduced into the USA, and identify their differences.
      Five isolates of T. equigenitalis associated with introductions into the USA from
      unique sources were sequenced using both short and long read chemistries allowing
      for complete assembly and annotation. These sequences were compared to previously
      published genomes as well as the short read sequences of the 200 isolates in the
      National Veterinary Services Laboratories' diagnostic repository to identify
      unique regions and genes, potential virulence factors, and characterize
      diversity. The 5 genomes varied in size by up to 100,000 base pairs, but averaged
      1.68 megabases. The majority of that diversity in size can be explained by repeat
      regions and 4 main regions of difference, which ranged in size from 15,000 to
      45,000 base pairs. The first region of difference contained mostly hypothetical
      proteins, the second contained the CRISPR, the third contained primarily
      hemagglutinin proteins, and the fourth contained primarily segments of a type IV
      secretion system. As expected and previously reported, little evidence of
      recombination was found within these genomes. Several additional areas of
      interest were also observed including a mechanism for streptomycin resistance and
      other virulence factors. A SNP distance comparison of the T. equigenitalis
      isolates and Mycobacterium tuberculosis complex (MTBC) showed that relatively, T.
      equigenitalis was a more diverse species than the entirety of MTBC.

PMID- 29584784
TI  - Statistical and Machine Learning forecasting methods: Concerns and ways forward.
AB  - Machine Learning (ML) methods have been proposed in the academic literature as
      alternatives to statistical ones for time series forecasting. Yet, scant evidence
      is available about their relative performance in terms of accuracy and
      computational requirements. The purpose of this paper is to evaluate such
      performance across multiple forecasting horizons using a large subset of 1045
      monthly time series used in the M3 Competition. After comparing the post-sample
      accuracy of popular ML methods with that of eight traditional statistical ones,
      we found that the former are dominated across both accuracy measures used and for
      all forecasting horizons examined. Moreover, we observed that their computational
      requirements are considerably greater than those of statistical methods. The
      paper discusses the results, explains why the accuracy of ML models is below that
      of statistical ones and proposes some possible ways forward. The empirical
      results found in our research stress the need for objective and unbiased ways to
      test the performance of forecasting methods that can be achieved through sizable
      and open competitions allowing meaningful comparisons and definite conclusions.

PMID- 29584783
TI  - Regional Outcome Evaluation Program (P.Re.Val.E.): Reduction of inequality in
      access to effective health care in the Lazio region of Italy (2012-2015).
AB  - BACKGROUND: Inequalities in health among groups of various socio-economic status
      (as measured by education, occupation, and income) constitute one of the main
      challenges for public health. Since 2006, the Lazio Regional Outcome Evaluation
      Program (P.Re.Val.E.), presents a set of indicators of hospital performance based
      on quality standards driven by strong clinical recommendations, and measures the
      variation in the access to effective health care for different population groups
      and providers in the Lazio Region. One of the aims of the program was to compare
      population subgroups in order to promote equity in service provision. Since June
      2013, a new management strategy has been put in place that assigned specific
      goals based on performance assessment to the chief executive officers of the
      hospitals. AIM: To evaluate whether, in recent years, there has been a reduction
      in the differential access to effective health care, among individuals with
      different educational levels. METHODS: We enrolled all patients discharged from
      both public and private hospitals of the Lazio region between 2012 and 2015,
      living in Lazio region. We analysed the proportion of patients with ST-elevation
      myocardial infarction (STEMI) treated with percutaneous coronary intervention
      within 90 minutes (primary PCI), the proportion of patients with hip fracture
      (HF) who underwent surgery within 2 days, and the proportion of women with
      primary C-section. We applied multivariate logistic regression models to assess
      the effect of educational level on health outcomes, adjusting for demographic
      characteristics and comorbidities that could affect the outcomes. For each year
      of the study period, we compared adjusted proportions of outcomes for the highest
      and the lowest level of education by using percentage differences. RESULTS: In
      the Lazio region, 44.6% of STEMI patients (N = 3,299) were treated with primary
      PCI, 54.4% of patients with hip fractures (N = 6,602) underwent surgery within 2
      days, and 27.7% of women without a previous C-section (N = 34,718) delivered via
      C-section, in 2015. The corresponding proportions in 2012 were 27.8%, 31.3% and
      31.5%, respectively. By comparing the adjusted proportions in patients with the
      highest education level (a university degree or higher) to those with the lowest
      level education level (None/Primary school), a decrease in the percentage
      difference was observed during the study period. In STEMI and delivery cohorts,
      the improvement of outcomes involved the least and the most educated patients,
      respectively, and the difference between the two educational levels was close to
      zero in 2015, whereas for hip patients, the improvement was more evident among
      the less educated patients. CONCLUSIONS: In the Lazio region, we observed a
      reduction in the differential access to effective heath care by educational
      level, in different clinical areas. Different factors might explain these
      results. On top of the public disclosure of outcome data, the management strategy
      applied in mid-2013 might have driven the overall improvement of the health
      system for the considered conditions, helping to achieve a fairer access to
      health.

PMID- 29584785
TI  - Relationships between anhedonia, suicidal ideation and suicide attempts in a
      large sample of physicians.
AB  - BACKGROUND: The relationships between anhedonia and suicidal ideation or suicide
      attempts were explored in a large sample of physicians using the interpersonal
      psychological theory of suicide. We tested two hypotheses: firstly, that there is
      a significant relationship between anhedonia and suicidality and, secondly, that
      anhedonia could mediate the relationships between suicidal ideation or suicide
      attempts and thwarted belongingness or perceived burdensomeness. METHODS: In a
      cross-sectional study, 557 physicians filled out several questionnaires measuring
      suicide risk, depression, using the abridged version of the Beck Depression
      Inventory (BDI-13), and demographic and job-related information. Ratings of
      anhedonia, perceived burdensomeness and thwarted belongingness were then
      extracted from the BDI-13 and the other questionnaires. RESULTS: Significant
      relationships were found between anhedonia and suicidal ideation or suicide
      attempts, even when significant variables or covariates were taken into account
      and, in particular, depressive symptoms. Mediation analyses showed significant
      partial or complete mediations, where anhedonia mediated the relationships
      between suicidal ideation (lifetime or recent) and perceived burdensomeness or
      thwarted belongingness. For suicide attempts, complete mediation was found only
      between anhedonia and thwarted belongingness. When the different components of
      anhedonia were taken into account, dissatisfaction-not the loss of interest or
      work inhibition-had significant relationships with suicidal ideation, whereas
      work inhibition had significant relationships with suicide attempts. CONCLUSIONS:
      Anhedonia and its component of dissatisfaction could be a risk factor for
      suicidal ideation and could mediate the relationship between suicidal ideation
      and perceived burdensomeness or thwarted belongingness in physicians.
      Dissatisfaction, in particular in the workplace, may be explored as a strong
      predictor of suicidal ideation in physicians.

PMID- 29584786
TI  - Chronic health conditions and school performance in first graders: A prospective
      cohort study.
AB  - OBJECTIVE: Children with chronic health conditions may perform poorer at school.
      Associations may be confounded by numerous social factors. We aimed to estimate
      the effects of a chronic health condition on overall school performance in first
      graders with an emphasis on rigorous adjustment for potential confounders.
      METHODS: A population-based cohort study was performed in the area of Mainz
      Bingen (Germany). In 2015 all preschoolers were approached and the presence of a
      chronic health condition was assessed by parental questionnaires and preschool
      health examination data. The identification of a chronic health condition was
      based on special health care needs and presence of a doctor's diagnosis out of 24
      school-relevant diseases. At the end of the first school year, overall school
      performance was assessed by teachers and rated on a 5-item scale ranging from -10
      to +10. RESULTS: Of 3683 children approached, 2003 were enrolled. Overall school
      performance was available for 1462 children (51% boys). Of these, 52% suffered
      from a chronic health condition. Compared to children without a chronic health
      condition, children with special health care needs (15%) performed worse at
      school (adjusted mean difference: -0.95, 95% CI: [-1.55; -0.35], P = 0.002).
      Children with a doctor's diagnosis but without special health care needs (37%)
      did not perform worse at school. The effect was further analysed considering the
      extent of special health care needed. CONCLUSIONS: Chronic health conditions
      affect overall school performance early in primary school. To identify
      academically at-risk children, a chronic health condition identification based on
      special health care needs may be used.

PMID- 29584787
TI  - Factors affecting walking ability in female patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the factors associated with gait parameters in female
      patients with rheumatoid arthritis (RA). METHODS: The gait analysis was performed
      in a large cohort of RA patients, and three basic gait parameters (step length,
      cadence and gait speed) were calculated. Clinical and laboratory data were also
      collected. Factors associated with gait parameters were analyzed using
      multivariable linear regression in the three models with forced entry. Then, we
      divided those patients with Health Assessment Questionnaire disability index
      (HAQ) scores <= 0.5 into two groups according to their gait speed that were
      compared to identify the characteristics of patients with a good HAQ score but
      poor walking ability. RESULTS: A total of 318 female patients were analyzed. Knee
      extension strength had the strongest positive association with all three gait
      parameters (P < 0.0001), while methotrexate use was also positively associated
      with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model
      1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score
      was negatively associated with step length and gait speed (step length, gait
      speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good
      HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait
      speed had higher disease activity scores (P < 0.05) and lower knee extension
      strength (P < 0.0001) than those with good HAQ scores and normal gait speed.
      CONCLUSIONS: High knee extension strength, low disease activity and
      administration of methotrexate were strongly associated with good walking ability
      in female patients with RA. And, even if patients showed good HAQ scores, about
      quarter of those patients had poor walking ability, and they showed higher
      disease activity, lower knee extension strength, compared to the patients with
      normal gait speed.

PMID- 29584788
TI  - IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Interleukin-17 (IL-17), a cytokine mainly secreted by Th17 cells,
      seems to play a significant role in the pathogenesis of rheumatoid arthritis
      (RA). Functional genetic polymorphisms in IL-17 and its receptor genes can
      influence either qualitatively or quantitatively their functions. Therefore, we
      aimed to study the impact of IL17-A and IL17RC polymorphisms on plasma level of
      IL-17 and RA susceptibility and severity. METHODS: In this context, IL
      17A*rs2275913 and IL-17RC*rs708567 polymorphisms were investigated together with
      the quantification of IL17 plasma level in 115 RA patients and 91 healthy control
      subjects matched in age, sex and ethnic origin. RESULTS: There were no
      statistically significant associations between IL-17A and IL-17RC studied
      polymorphisms and RA susceptibility. In contrast, IL-17A plasma levels were
      significantly higher in patients (55.07 pg/ml) comparatively to controls (4.75
      pg/ml), p<10E-12. A ROC curve was used to evaluate the performance of plasma IL
      17 in detecting RA. Given 100% specificity, the highest sensitivity of plasma IL
      17A was 61.7% at a cut-off value of 18.25 pg/ml; p < 10E-21, CI = [0.849-0.939].
      Analytic results showed that the IgM-rheumatoid factor and anti-CCP antibodies
      were significantly less frequent in patients with the IL-17RC*A/A genotype than
      those carrying *G/G and *G/A genotypes; p = 0.013 and p = 0.015, respectively.
      Otherwise, IL-17 plasma levels' analysis showed a significant association with
      the activity of RA (DAS28>=5.1 = 74.71 pg/ml vs. DAS28<5.1 = 11.96 pg/ml), p<10E
      6. CONCLUSION: IL-17A*rs2275913 (G/A) and IL-17RC*rs708567 (G/A) polymorphisms
      did not seem to influence RA susceptibility in Tunisian population. This result
      agrees with those reported previously. Plasma IL-17A level seems to be predictive
      of severe RA occurrence.

PMID- 29584789
TI  - The effect of CAG repeats length on differences in hirsutism among healthy
      Israeli women of different ethnicities.
AB  - PURPOSE: Variations in the degree of hirsutism among women of different ethnic
      backgrounds may stem from multiple etiologies. Shorter length of the polymorphic
      CAG repeats of the androgen receptor (AR) gene may be associated with increased
      activity of the receptor leading to hirsutism. We hypothesized that there are
      ethnic differences in the degree of hirsutism that is unrelated to androgen
      levels among Israeli women, and that the CAG repeats length may contribute to
      these differences. Anti-androgenic therapies, such as spironolactone, could be
      suggested if a shorter CAG repeats length is found to affect the difference in
      the degree of hirsutism between the ethnic groups. METHODS: Healthy Israeli
      Jewish women aged 18-45 years of Ashkenazi and non-Ashkenazi origin were invited
      to participate. Hirsutism was assessed using the simplified Ferriman-Gallwey
      (sFG) score, and serum total testosterone levels were measured as well. The CAG
      repeats length was determined by PCR. Methylation-sensitive methods were used to
      detect the fractional activity of each allele, and the weighted mean was
      calculated for the CAG repeats length. RESULTS: One-hundred and eight women were
      recruited (49 Ashkenazi and 59 non-Ashkenazi). The Ashkenazi women had a
      significantly lower degree of hirsutism (P<0.01), lower mean BMI (P = 0.003),
      total testosterone levels (P = 0.017), and longer weighted bi-allelic CAG repeats
      mean (P = 0.015) compared to non-Ashkenazi women. For the group as a whole, there
      was a significant negative correlation between the number of CAG repeats in the
      AR gene and the sFG score, while the number of repeats was not related to
      testosterone levels. Stepwise logistic regression revealed that ethnic origin and
      the CAG repeats length were the strongest factors affecting hirsutism (P<0.001, P
      = 0.03, respectively). CONCLUSIONS: There is a significant difference in the
      degree of hirsutism between Ashkenazi and non-Ashkenazi women in Israel that is
      partially explained by CAG repeats length.

PMID- 29584791
TI  - Respiratory isolation for tuberculosis: the experience of Indigenous peoples on
      the Canadian prairies.
AB  - Setting: The Prairie provinces of Canada. Objective: To understand how Indigenous
      peoples with infectious pulmonary tuberculosis living in different community
      settings in the Prairie provinces of Canada experience respiratory isolation.
      Design: Using an exploratory qualitative approach, we interviewed participants
      living in urban centres, non-remote reserve settings and remote and isolated
      reserve settings. Results: Through qualitative content analysis of 48 interviews,
      we determined that participants experienced feelings of confinement regardless of
      the community setting in which they lived. Participants also experienced family
      and social disconnect, but the experience was more potent for the remote and
      isolated reserve participants, who were required to be flown out of their home
      communities to receive treatment, and for those urban centre and non-remote
      reserve participants who lacked social connections. The roles of past experiences
      with sanitoria and of family in providing social support are discussed.
      Conclusions: The conclusions of this study focus on examining isolation policies
      and improving the hospital isolation experience.

PMID- 29584790
TI  - Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk
      of adverse outcomes, a population-based study.
AB  - OBJECTIVES: To determine risk factors for short and long umbilical cord,
      entanglement and knot. Explore their associated risks of adverse maternal and
      perinatal outcome, including risk of recurrence in a subsequent pregnancy. To
      provide population based gestational age and sex and parity specific reference
      ranges for cord length. DESIGN: Population based registry study. SETTING: Medical
      Birth Registry of Norway 1999-2013. POPULATION: All singleton births (gestational
      age>22weeks<45 weeks) (n = 856 300). METHODS: Descriptive statistics and odds
      ratios of risk factors for extreme cord length and adverse outcomes based on
      logistic regression adjusted for confounders. MAIN OUTCOME MEASURES: Short or
      long cord (<10th or >90th percentile), cord knot and entanglement, adverse
      pregnancy outcomes including perinatal and intrauterine death. RESULTS:
      Increasing parity, maternal height and body mass index, and diabetes were
      associated with increased risk of a long cord. Large placental and birth weight,
      and fetal male sex were factors for a long cord, which again was associated with
      a doubled risk of intrauterine and perinatal death, and increased risk of adverse
      neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were
      associated with a short cord, which was associated with increased risk of fetal
      malformations, placental complications, caesarean delivery, non-cephalic
      presentation, perinatal and intrauterine death. At term, cord knot was associated
      with a quadrupled risk of perinatal death. The combination of a cord knot and
      entanglement had a more than additive effect to the association to perinatal
      death. There was a more than doubled risk of recurrence of a long or short cord,
      knot and entanglement in a subsequent pregnancy of the same woman. CONCLUSION:
      Cord length is influenced both by maternal and fetal factors, and there is
      increased risk of recurrence. Extreme cord length, entanglement and cord knot are
      associated with increased risk of adverse outcomes including perinatal death. We
      provide population based reference ranges for umbilical cord length.

PMID- 29584792
TI  - Risk factors for unfavourable treatment outcome among new smear-positive
      pulmonary tuberculosis cases in China.
AB  - Setting: Three projects of the Fund for Innovative DOTS Expansion through Local
      Initiatives to Stop TB. Objectives: To assess unfavourable treatment outcomes
      (UTOs), including failure, died, loss to follow-up (LTFU), transferred out and
      unknown outcome, and to identify risk factors associated with UTOs. Design: This
      was a cross-sectional study using routine programme data. Results: Of 30 277 new
      smear-positive tuberculosis (TB) patients, 4261 (14.1%) had UTOs: 2048 (6.8%)
      LTFU, 1418 (4.7%) transferred out, 390 (1.3%) died, 340 (1.1%) failed and 65
      (0.2%) had an unknown outcome. Risk factors for LTFU (including LTFU, transfer
      out and unknown outcome) were residing in Anhui, age > 55 years, service delay >
      10 days, patient delay < 30 days, directly observed treatment (DOT) provided by a
      family member or others and unknown DOT provider. The outcome of 'died' was
      associated with residing in Shaanxi, age > 55 years, male sex, patient delay > 30
      days and unknown DOT provider. 'Failed' was associated with having unlimited
      access to health services, patient delay of >30 days and unknown DOT provider.
      Conclusion: This study highlights the predominance of lost patients among UTOs.
      Patients with family members or other non-medical DOT providers or unknown DOT
      providers had a high risk of a UTO. There is an urgent need to address these
      service-related factors.

PMID- 29584793
TI  - Characteristics and management of presumptive tuberculosis in public health
      facilities in Malawi, 2014-2016.
AB  - Setting: Public health facilities providing tuberculosis (TB) and human
      immunodeficiency virus (HIV) services in Malawi. Objectives: Using routinely
      collected health service delivery data to describe trends in HIV ascertainment
      and use of the Xpert(r) MTB/RIF assay to diagnose TB among HIV-positive
      presumptive TB cases. Design: This was an implementation study of presumptive TB
      cases who sought care from 21 facilities between April 2014 and June 2016.
      Descriptive statistics were used to summarise patient, facility and service level
      characteristics. Results: Of 28 567 presumptive TB cases analysed, 23 198 (81%)
      had known HIV status. The proportion of ascertained HIV status in presumptive TB
      cases increased over the study period. HIV prevalence was 49%, with 73% of HIV
      positive presumptive TB cases on antiretroviral therapy. Access to Xpert ranged
      between 37% and 63% per quarter among HIV-positive presumptive TB patients with
      smear-negative sputum results. Of 7829 patients with documented Xpert results,
      68% were HIV-positive. Conclusion: After the introduction of registers with HIV
      related variables, HIV ascertainment among presumptive TB cases increased over
      time. Access to Xpert was suboptimal among HIV-positive presumptive TB cases.
      Further collaboration between national TB and HIV programmes may facilitate
      increased use of Xpert for HIV-positive patients with presumptive TB who seek
      care in public health facilities.

PMID- 29584794
TI  - Occupational tuberculosis in South Africa: are health care workers adequately
      protected?
AB  - Setting: A provincial tertiary hospital in Gauteng province, South Africa, with a
      high burden of tuberculosis (TB) patients and high risk of TB exposure among
      health care workers (HCWs). Objective: To determine HCWs' adherence to
      recommended TB infection prevention and control practices, TB training and access
      to health services and HCW TB rates. Design: Interviews with 285 HCWs using a
      structured questionnaire as part of a large, international mixed-methods study.
      Results: Despite 10 HCWs (including seven support HCWs) acquiring clinical TB
      during their period of employment, 62.8% of interviewees were unaware of the
      hospital's TB management protocol. Receipt of training was low (34.5% of all HCWs
      and <5% of support HCWs trained on TB transmission; 27.5% of nurses trained on
      respirator use), as was use of respiratory protection (44.5% of HCWs trained on
      managing TB patients). Support HCWs were over 36 times more likely to use
      respiratory protection if trained; nurses who were trained were approximately 40
      times more likely to use respirators if they were readily available. Conclusion:
      Improved coordination and uptake of TB infection prevention training is urgently
      needed, especially for non-clinical HCWs in settings of regular exposure to TB
      patients. Adequate supplies of appropriate respiratory protection must be made
      available.

PMID- 29584795
TI  - Sensitivity, completeness and agreement of the tuberculosis electronic system in
      Ho Chi Minh City, Viet Nam.
AB  - Setting: Since 2011, tuberculosis (TB) clinics in Ho Chi Minh City (HCMC), Viet
      Nam, have been entering data from a paper-based TB treatment register into an
      electronic database known as VITIMES (Viet Nam TB Information Management
      Electronic System), which is currently used in parallel with the paper system.
      Objective: To evaluate the sensitivity, completeness and agreement of data in
      VITIMES with that of paper-based registers among TB patients co-infected with the
      human immunodeficiency virus (HIV) being treated for TB in HCMC. Design: This was
      a retrospective data review of all TB-HIV patients receiving anti-tuberculosis
      treatment in each of the 24 district TB clinics in HCMC in 2013. Data were
      abstracted from the paper-based TB treatment registers at district level and
      extracted electronically at the provincial level. Records were matched based on
      name, age and address. The sensitivity, completeness and agreement of the
      electronic data were compared with data from the paper system. Results: The
      findings showed that the electronic system had high sensitivity (99.2%), high
      completeness (87-99%) and high agreement (kappa 0.78-0.97) for all variables.
      Conclusion: The results of this study suggest that data are being correctly
      entered into VITIMES and that patient data can be directly entered into VITIMES
      instead of having a parallel, paper-based system.

PMID- 29584796
TI  - Should sputum-negative presumptive TB patients be actively followed to identify
      missing cases in India?
AB  - Setting: Sputum smear microscopy, the primary diagnostic tool used for diagnosis
      of tuberculosis (TB) in India's Revised National TB Control Programme (RNTCP),
      has low sensitivity, resulting in a significant number of TB cases reported as
      sputum-negative. As the revised guidelines pose challenges in implementation,
      sputum-negative presumptive TB (SNPT) patients are subjected to 2 weeks of
      antibiotics, followed by chest X-ray (CXR), resulting in significant loss to care
      among these cases. Objective: To determine whether reducing delays in CXR would
      yield additional TB cases and reduce initial loss to follow-up for diagnosis
      among SNPT cases. Methods: In an ongoing intervention in five districts of
      Maharashtra, SNPT patients were offered upfront CXR. Results: Of 119 male and 116
      female SNPT patients with a mean age of 45 years who were tested by CXR, 32 (14%)
      were reported with CXR suggestive of TB. Administering upfront CXR in SNPT
      patients yielded twice as many additional cases, doubling the proportion of cases
      detected among all those tested as against administering CXR 2 weeks after smear
      examination. Conclusion: Our interventional study showed that the yield of TB
      cases was significantly greater when upfront CXR examination was undertaken
      without waiting for a 2-week antibiotic trial.

PMID- 29584797
TI  - What drives 'first-time testers' to test for HIV at community-based HIV testing
      services?
AB  - Drivers of and barriers to testing are not well understood for those who have
      never been tested previously and now self-initiate at a community-based human
      immuno-deficiency virus (HIV) testing service (CB-HTS). This descriptive study
      enrolled 229 first-time testers. Participants completed an electronic
      questionnaire. The majority reported fear and (non) accessibility of HTS as
      barriers to testing (40% and 24%, respectively). Wanting 'to know my status' and
      the immediate opportunity to test were reported as drivers of testing (41% and
      35%, respectively). Addressing fear of testing and providing an easily accessible
      opportunity to test may go some way to encouraging those previously untested
      individuals to test.

PMID- 29584798
TI  - Access to human immunodeficiency virus testing services in Cape Town, South
      Africa: a user perspective.
AB  - Objective: To compare the availability, affordability and acceptability of two
      non-governmental organisation (NGO) led human immunodeficiency virus (HIV)
      testing service (HTS) modalities (mobile and stand-alone) with HTS at a public
      primary health care facility. Methods: Adult participants who self-referred for
      HIV testing were enrolled as they exited the HTS modalities. Data collection
      using an electronic questionnaire took place between November 2014 and February
      2015. Logistic regression analysis was used to assess differences in the
      participants' demographic characteristics and the availability, affordability and
      acceptability of HTS between modalities. Results: There were 130 participants
      included in the study. Irrespective of modality, most participants walked to the
      service provider, had a travel time of <30 min and reported no costs.
      Participants were less likely to report waiting times of ?30 min compared to <15
      min at the mobile modality compared to the public facility (aOR < 0.001, 95%CI <
      0.001-0.03). Conclusion: Irrespective of modality, HIV testing services were
      available and affordable in our study. Waiting times were significantly higher at
      the public facility compared to the NGO modalities. As South Africa moves toward
      achieving the first UNAIDS target, it is essential not only to make HTS available
      and affordable, but also to ensure that these services are acceptable, especially
      to those who have never been tested before.

PMID- 29584799
TI  - Enhancing tuberculosis patient detection and care through community volunteers in
      the urban poor, The Philippines.
AB  - Setting: The Research Institute of Tuberculosis/Japan Anti-Tuberculosis
      Association Philippines is a local non-governmental organisation (NGO)
      established in 2008 to improve access to tuberculosis (TB) services. Community
      health volunteers (CHVs) from NGO referring facilities were engaged to assist in
      local TB control activities. Objective: To describe the activities of the CHVs
      and the barriers experienced by patients with presumptive TB in seeking health
      care to treatment as documented on a master list, and to identify the CHVs'
      challenges in community TB care implementation. Design: This was a retrospective
      evaluation with a non-experimental design reviewing the presumptive TB master
      list and TB reports and conducting a free discussion session (FDS) in 2012.
      Results: Of the 78% (281/362) of referred presumptive TB patients who accessed a
      DOTS facility, 69% (194/281) underwent a diagnostic examination and 42% (81/194)
      were diagnosed with active TB. Of the 93% (75/81) initiated on treatment, 92%
      (69/75) were successfully treated. The CHVs contributed approximately 3%
      (75/2534) to the total TB cases diagnosed at the DOTS facilities. In the FDS,
      barriers evoked in seeking health care for treatment were transfer of residence
      and lack of interest in seeking a consultation. In 2012, the CHV attrition rate
      was 55% (80/145). Conclusion: The CHVs assisted in enhancing access to TB care
      and case detection. Sustainability of the CHVs' efforts should be explored to
      retain them in the programme.

PMID- 29584800
TI  - The sixth vital sign: HIV status assessment and severe illness triage in Uganda.
AB  - Setting: Four in-patient health facilities in western Uganda. Objective: To
      determine the impact of an innovative multi-modal quality improvement program on
      human immunodeficiency virus (HIV) status assessment and the impact of HIV status
      on severe illness conditions and mortality. Design: This was a staggered, pre
      post quasi-experimental study designed to assess a multi-modal intervention
      (collaborative improvement meetings, audit and feedback, clinical mentoring) for
      improving quality of care following formal training in the management of severe
      illness in low-income settings. Results: From August 2014 to May 2015, 5759
      patients were hospitalized, of whom 2451 (42.6%) had their HIV status assessed;
      395 (16.1%) were HIV-infected. HIV-infected patients were significantly more
      likely to meet criteria for shock (27.5% vs. 15.1%, risk ratio [RR] 1.8, 95%
      confidence interval [CI] 1.7-1.9, P < 0.001) and severe respiratory distress
      (6.7% vs. 4.3%, RR 1.5, 95%CI 1.2-2.0, P < 0.001), and were significantly more
      likely to die in hospital (12.0% vs. 2.9%, RR 4.1, 95%CI 3.2-5.4, P < 0.001).
      There was no evidence of improved HIV status assessment during the intervention
      period (36.5% vs. 44.8%, +8.3%, 95%CI -8.3 to 24.8, P = 0.33). Conclusions:
      Hospitalized HIV-infected patients in western Uganda are at high risk for severe
      illness and death. Novel quality improvement strategies are needed to enhance
      hospital-based HIV testing in high-burden settings.

PMID- 29584801
TI  - Immunochip Meta-Analysis of Inflammatory Bowel Disease Identifies Three Novel
      Loci and Four Novel Associations in Previously Reported Loci.
AB  - Background and Aims: Recent meta-analysis of genome-wide association studies have
      identified over 241 inflammatory bowel disease susceptibility loci. However, the
      known variants only account for a fraction of inflammatory bowel disease
      heritability. To identify additional susceptibility loci, we performed a trans
      ethnic meta-analysis as well as an Asian-specific meta-analysis, using all
      published Immunochip association results of inflammatory bowel disease. Methods:
      An inverse-variance fixed-effects meta-analysis was carried out across Korean and
      East Asian Immunochip datasets of 4156 cases and 4904 controls [Asian ancestry].
      A trans-ethnic meta-analysis of inflammatory bowel disease was performed together
      with the European datasets of 38 155 cases and 48 485 controls genotyped on the
      immunochip using a Bayesian approach, Meta-Analysis of Trans-ethnic Association
      studies [MANTRA]. Results: We identified seven novel associations, including
      three novel susceptibility loci at MYO10-BASP1, PPP2R3C/KIAA0391/PSMA6/NFKB1A and
      LRRK1 as well as four novel secondary associations within previously known loci
      at NCF4, TSPAN32, CIITA and VANGL2. The new loci further implicate alterations in
      B cell biology in Crohn's disease pathogenesis. The effects of five loci were
      universal across European and Asian ancestries, whereas the NCF4 and CIITA loci
      showed significant heterogeneity between European and East Asian populations. In
      addition, 103 previously known IBD loci showed supporting evidence of association
      with nominal significance [p < 0.05] in Asians. Conclusions: Our findings of new
      loci not previously associated with IBD support the importance of studying
      inflammatory bowel disease genetics in diverse populations.

PMID- 29584804
TI  - Variable lymphocyte receptors play a key role in neutralization and opsonization
      in the lamprey.

PMID- 29584803
TI  - Involvement of acid-sensing ion channel 1a in gastric carcinoma cell migration
      and invasion.
AB  - Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has
      been reported to promote carcinoma cell proliferation as well as migration. In
      this study, we explored the effect of ASIC1a on migration and invasion of gastric
      carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent
      normal tissues from 16 patients by immunohistochemistry. Reverse transcription
      real-time PCR and immunoblotting were conducted to assess the ASIC1a expression
      levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA
      (shRNA). Wound healing and transwell invasion assays were utilized to detect
      metastasis and invasion following ASIC1a silencing. Tumor formation was used to
      detect the role of ASIC1a in tumorigenicity in vivo. It was found that ASIC1a
      expression level was significantly higher in GC tissues showing postoperative
      metastasis compared with non-metastasis and non-tumor tissues. Moreover,
      silencing of ASIC1a with shRNA significantly down-regulated ASIC1a expression and
      reduced GC cell migration and invasion. A moderately acidic extracellular
      environment inhibited GC cell viability. Furthermore, ASIC1a shRNA caused
      inhibition of tumorigenicity in vivo. Our study is the first report of
      attenuating the malignant phenotype of GC in vitro and in vivo by suppressing
      ASIC1a, and suggests a novel approach to study the relationship between ASICs and
      GC cell migration and invasion.

PMID- 29584805
TI  - A Ten Year Immunopersistence Study of Hepatitis E Antibodies in Rural Bangladesh.
AB  - Hepatitis E virus (HEV) is a major cause of acute, viral hepatitis in Southeast
      Asia. Several studies have suggested that antibody persistence after HEV
      infection may be transient, possibly increasing the risk of re-infection and
      contributing to the frequency of outbreaks in HEV endemic regions. The specific
      conditions under which antibodies to HEV are lost, or "sero-reversion" occurs,
      are poorly understood. Here, one hundred participants from population-based
      studies in rural Bangladesh were revisited in 2015, ten years after a documented
      HEV infection to examine long-term antibody persistence. Twenty percent (95%
      confidence interval: 12.0, 28.0) no longer had detectable antibodies at follow
      up, suggesting that antibodies generally persist for at least a decade after
      infection in rural Bangladesh. Those who were seronegative at follow-up were
      generally younger at infection than those who remained positive (14.4 years
      versus 33.6 years, P > 0.0001). This age-dependent antibody loss could partially
      explain cross-sectional sero-prevalence data from South East Asia where children
      have reportedly low antibody prevalence. The results of this study provide new
      insight into the immunological persistence of HEV infection in a micronutrient
      deficient rural population of South Asia, highlighting the importance of age at
      infection in the ability to produce long-lasting antibodies against HEV.

PMID- 29584802
TI  - Perturbed autophagy and DNA repair converge to promote neurodegeneration in
      amyotrophic lateral sclerosis and dementia.
AB  - Maintaining genomic stability constitutes a major challenge facing cells. DNA
      breaks can arise from direct oxidative damage to the DNA backbone, the
      inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due
      to transcriptionally-derived RNA/DNA hybrids (R-loops). The progressive
      accumulation of DNA breaks has been linked to several neurological disorders.
      Recently, however, several independent studies have implicated nuclear and
      mitochondrial genomic instability, perturbed co-transcriptional processing, and
      impaired cellular clearance pathways as causal and intertwined mechanisms
      underpinning neurodegeneration. Here, we discuss this emerging paradigm in the
      context of amyotrophic lateral sclerosis and frontotemporal dementia, and outline
      how this knowledge paves the way to novel therapeutic interventions.

PMID- 29584806
TI  - Placental Weight and Risk of Cryptorchidism and Hypospadias in the Collaborative
      Perinatal Project.
AB  - Cryptorchidism and hypospadias are the most common congenital anomalies of the
      genitourinary tract in males, but their etiology remains unclear. Placental
      insufficiency has been suggested to be linked to both conditions. Placental
      weight is a commonly used proxy measure for placental insufficiency; thus, we
      examined placental weight and other placental characteristics in relation to
      cryptorchidism and hypospadias in the Collaborative Perinatal Project, a US
      mother-child cohort study. Pregnant women were recruited between 1959 and 1965.
      The analysis contrasted boys with cryptorchidism (n = 413) and boys with
      hypospadias (n = 145) with boys without cryptorchidism (n = 23,799) and boys
      without hypospadias (n = 22,326). Odds ratios and 95% confidence intervals were
      calculated using unconditional logistic regression. In categorical analyses in
      which the middle tertile was the referent, cryptorchidism was inversely
      associated with placental weight (odds ratio = 0.66, 95% confidence interval:
      0.46, 0.95) among white boys and positively associated with the lowest tertile of
      placental weight among black boys (odds ratio = 1.70, 95% confidence interval:
      1.11, 2.59). We conclude that lower placental weight may be related to risk of
      cryptorchidism. Further investigation of placental functioning may offer insights
      into the etiology of cryptorchidism.

PMID- 29584807
TI  - Pain assessment in the older population: what the literature says.
AB  - Assessment of pain in the older adult presents a number of challenges, especially
      related to communication. This commentary summarises the revised evidence-based
      Guidelines on the Assessment of Pain in Older Adults which have been developed by
      the British Pain Society and British Geriatrics Society. The guideline summarises
      the pain assessment tools that have been developed and validated for use in the
      older population. Recommendations are made for use of specific tools in older
      people and in those with dementia. The need for education and training of health
      care professionals is emphasised. Gaps in the evidence are identified as subjects
      for future research. It is hoped that the guideline will improve recognition of
      pain in older people, and help to drive the future research agenda.

PMID- 29584808
TI  - Urocortin-2 improves right ventricular function and attenuates pulmonary arterial
      hypertension.
AB  - Aims: Pulmonary arterial hypertension (PAH) is a devastating disease and
      treatment options are limited. Urocortin-2 (Ucn-2) has shown promising
      therapeutic effects in experimental and clinical left ventricular heart failure
      (HF). Our aim was to analyse the expression of Ucn-2 in human and experimental
      PAH, and to investigate the effects of human Ucn-2 (hUcn-2) administration in
      rats with monocrotaline (MCT)-induced pulmonary hypertension (PH). Methods and
      results: Tissue samples were collected from patients with and without PAH and
      from rats with MCT-induced PH. hUcn-2 (5 MUg/kg, bi-daily, i.p., for 10 days) or
      vehicle was administered to male wistar rats subjected to MCT injection or to
      pulmonary artery banding (PAB) to induce right ventricular (RV) overload without
      PAH. Expression of Ucn-2 and its receptor was increased in the RV of patients and
      rats with PAH. hUcn-2 treatment reduced PAH in MCT rats, resulting in decreased
      morbidity, improved exercise capacity and attenuated pulmonary arterial and RV
      remodelling and dysfunction. Additionally, RV gene expression of hypertrophy and
      failure signalling pathways were attenuated. hUcn-2 treatment also attenuated PAB
      induced RV hypertrophy. Conclusions: Ucn-2 levels are altered in human and
      experimental PAH. hUcn-2 treatment attenuates PAH and RV dysfunction in MCT
      induced PH, has direct anti-remodelling effects on the pressure-overloaded RV,
      and improves pulmonary vascular function.

PMID- 29584809
TI  - Floral morphology and morphogenesis in Camptotheca (Nyssaceae), and its
      systematic significance.
AB  - Background and Aims: Camptotheca is endemic to China and there are limited data
      about the breeding system and morphogenesis of the flowers. Camptotheca is
      thought to be related to Nyssa and Davidia in Nyssaceae, which has sometimes been
      included in Cornaceae. However, molecular phylogenetic studies confirmed the
      inclusion of Camptotheca in Nyssaceae and its exclusion from Cornaceae. The aim
      of this study was to reveal developmental features of the inflorescence and
      flowers in Camptotheca to compare with related taxa in Cornales. Methods:
      Inflorescences and flowers of Camptotheca acuminata at all developmental stages
      were collected and studied with a scanning electron microscope and stereo
      microscope. Key Results: Camptotheca has botryoids which are composed of several
      capitate floral units (FUs) that are initiated acropetally. On each FU, flowers
      are grouped in dyads that are initiated acropetally. All floral organs are
      initiated centripetally. Calyx lobes are restricted to five teeth. The
      hypanthium, with five toothed calyx lobes, is adnate to the ovary. The five
      petals are free and valvate. Ten stamens are inserted in two whorls around the
      central depression, in which the style is immersed. Three carpels are initiated
      independently but the ovary is syncarpous and unilocular. The ovule is unitegmic
      and heterotropous. Inflorescences are functionally andromonoecious varying with
      the position of the FUs on the inflorescence system. Flowers on the upper FU
      often have robust styles and fully developed ovules. Flowers on the lower FU have
      undeveloped styles and aborted ovules, and the flowers on the middle FU are
      transitional. Conclusions: Camptotheca possesses several traits that unify it
      with Nyssa, Mastixia and Diplopanax. Inflorescence and floral characters support
      a close relationship with Nyssaceae and Mastixiaceae but a distant relationship
      with Cornus. Our results corroborate molecular inferences and support a separate
      family Nyssaceae.

PMID- 29584810
TI  - Identification of miR-9-5p as direct regulator of ABCA1 and HDL-driven reverse
      cholesterol transport in circulating CD14+ cells of patients with metabolic
      syndrome.
AB  - Aims: Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors
      associated with atherosclerosis and low-grade inflammation. Using unbiased
      expression screenings in peripheral blood mononuclear cells, we depict here a
      novel expression chart of 678 genes and 84 microRNAs (miRNAs) controlling
      inflammatory, immune and metabolic responses. In order to further elucidate the
      link between inflammation and the HDL cholesterol pathway in MS, we focussed on
      the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player
      in cholesterol efflux (CE). Methods and results: ABCA1 mRNA levels are suppressed
      in CD14+ cells of MS patients and are negatively correlated to body mass index
      (BMI), insulin-resistance (HOMA-IR) and cardiovascular risk, and positively to
      HDL cholesterol and CE. miRNA target in silico prediction identified a putative
      modulatory role of ABCA1 for the nuclear factor kappa-light-chain-enhancer of
      activated B cell (NF-kappaB) target miR-9-5p, whose expression pattern was up
      regulated in CD14+ cells of MS patients, positively correlated to BMI, HOMA-IR,
      and triglycerides, and negatively to ABCA1 mRNA levels, HDL cholesterol and CE.
      Ectopic gain and loss of miR-9-5p function in macrophages modulated ABCA1 mRNA
      and protein levels, ABCA1 miRNA 3'-untranslated region target sequence reporter
      assay, and CE into HDL, thus confirming ABCA1 as a target of miR-9-5p.
      Conclusions: We identified the NF-kappaB target miR-9-5p as a negative regulator
      of ABCA1 adding a novel target pathway in the relationship between inflammation
      and HDL-driven reverse cholesterol transport for prevention or treatment of
      atherosclerosis in MS.

PMID- 29584811
TI  - Learned protein embeddings for machine learning.
AB  - Motivation: Machine-learning models trained on protein sequences and their
      measured functions can infer biological properties of unseen sequences without
      requiring an understanding of the underlying physical or biological mechanisms.
      Such models enable the prediction and discovery of sequences with optimal
      properties. Machine-learning models generally require that their inputs be
      vectors, and the conversion from a protein sequence to a vector representation
      affects the model's ability to learn. We propose to learn embedded
      representations of protein sequences that take advantage of the vast quantity of
      unmeasured protein sequence data available. These embeddings are low-dimensional
      and can greatly simplify downstream modeling. Results: The predictive power of
      Gaussian process models trained using embeddings is comparable to those trained
      on existing representations, which suggests that embeddings enable accurate
      predictions despite having orders of magnitude fewer dimensions. Moreover,
      embeddings are simpler to obtain because they do not require alignments,
      structural data, or selection of informative amino-acid properties. Visualizing
      the embedding vectors shows meaningful relationships between the embedded
      proteins are captured. Availability and implementation: The embedding vectors and
      code to reproduce the results are available at
      https://github.com/fhalab/embeddings_reproduction/. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29584814
TI  - Oral diseases as a cause of pain in older people.

PMID- 29584812
TI  - Landmark Models for Optimizing the Use of Repeated Measurements of Risk Factors
      in Electronic Health Records to Predict Future Disease Risk.
AB  - The benefits of using electronic health records (EHRs) for disease risk screening
      and personalized health-care decisions are being increasingly recognized. Here we
      present a computationally feasible statistical approach with which to address the
      methodological challenges involved in utilizing historical repeat measures of
      multiple risk factors recorded in EHRs to systematically identify patients at
      high risk of future disease. The approach is principally based on a 2-stage
      dynamic landmark model. The first stage estimates current risk factor values from
      all available historical repeat risk factor measurements via landmark-age
      specific multivariate linear mixed-effects models with correlated random
      intercepts, which account for sporadically recorded repeat measures, unobserved
      data, and measurement errors. The second stage predicts future disease risk from
      a sex-stratified Cox proportional hazards model, with estimated current risk
      factor values from the first stage. We exemplify these methods by developing and
      validating a dynamic 10-year cardiovascular disease risk prediction model using
      primary-care EHRs for age, diabetes status, hypertension treatment, smoking
      status, systolic blood pressure, total cholesterol, and high-density lipoprotein
      cholesterol in 41,373 persons from 10 primary-care practices in England and Wales
      contributing to The Health Improvement Network (1997-2016). Using cross
      validation, the model was well-calibrated (Brier score = 0.041, 95% confidence
      interval: 0.039, 0.042) and had good discrimination (C-index = 0.768, 95%
      confidence interval: 0.759, 0.777).

PMID- 29584813
TI  - Yoga-based exercise improves health-related quality of life and mental well-being
      in older people: a systematic review of randomised controlled trials.
AB  - Objective: health-related quality of life (HRQOL) and mental well-being are
      associated with healthy ageing. Physical activity positively impacts both HRQOL
      and mental well-being. Yoga is a physical activity that can be modified to suits
      the needs of older people and is growing in popularity. We conducted a systematic
      review with meta-analysis to determine the impact of yoga-based exercise on HRQOL
      and mental well-being in people aged 60+. Methods: searches were conducted for
      relevant trials in the following electronic databases; MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials, CINAHL, Allied and Complementary Medicine
      Database, PsycINFO and the Physiotherapy Evidence Database (PEDro) from inception
      to January 2017. Trials that evaluated the effect of physical yoga on HRQOL
      and/or on mental well-being in people aged 60+ years were included. Data on HRQOL
      and mental well-being were extracted. Standardised mean differences and 95%
      confidence intervals (CI) were calculated using random effects models.
      Methodological quality of trials was assessed using the PEDro scale. Results:
      twelve trials of high methodological quality (mean PEDro score 6.1), totalling
      752 participants, were identified and provided data for the meta-analysis. Yoga
      produced a medium effect on HRQOL (Hedges' g = 0.51, 95% CI 0.25-0.76, 12 trials)
      and a small effect on mental well-being (Hedges' g = 0.38, 95% CI 0.15-0.62, 12
      trials). Conclusion: yoga interventions resulted in small to moderate
      improvements in both HRQOL and mental well-being in people aged 60+ years.
      Further, research is needed to determine the optimal dose of yoga to maximise
      health impact. PROSPERO registration number: (CRD42016052458).

PMID- 29584816
TI  - Erratum.

PMID- 29584815
TI  - Erratum.

PMID- 29584817
TI  - Cardioprotection - is no the answer? A renewed look at nitric oxide signalling in
      cardiomyocytes.

PMID- 29584818
TI  - RE: "DIETARY PROTEIN INTAKE AND EARLY MENOPAUSE IN THE NURSES' HEALTH STUDY II".

PMID- 29584820
TI  - EM algorithms for fitting multistate cure models.
AB  - Multistate cure models are multistate models in which transitions into one or
      more of the states cannot occur for a fraction of the population. In the study of
      cancer, multistate cure models can be used to identify factors related to the
      rate of cancer recurrence, the rate of death before and after recurrence, and the
      probability of being cured by initial treatment. However, the previous method for
      fitting multistate cure models requires substantial custom programming, making
      these valuable models less accessible to analysts. In this article, we present an
      Expectation-Maximization (EM) algorithm for fitting the multistate cure model
      using maximum likelihood. The proposed algorithm makes use of a weighted
      likelihood representation allowing it to be easily implemented with standard
      software and can incorporate either parametric or non-parametric baseline hazards
      for the state transition rates. A common complicating feature in cancer studies
      is that the follow-up times for recurrence and death may differ. Additionally, we
      may have missingness in the covariates. We propose a Monte Carlo EM (MCEM)
      algorithm for fitting the multistate cure model in the presence of covariate
      missingness and/or unequal follow-up of the two outcomes, we describe a novel
      approach for obtaining standard errors, and we provide some software. Simulations
      demonstrate good algorithmic performance as long as the modeling assumptions are
      sufficiently restrictive. We apply the proposed algorithm to a study of
      recurrence and death in patients with head and neck cancer.

PMID- 29584819
TI  - Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration.
AB  - Aims: Long noncoding RNAs (lncRNAs) are critical regulators of cardiovascular
      lineage commitment and heart wall development, but their roles in regulating
      endogenous cardiac regeneration are unclear. The present study investigated the
      role of human-derived lncRNA in regulating endogenous cardiac regeneration as
      well as the underlying mechanisms. Methods and results: We compared RNA
      sequencing data from human foetal and adult hearts and identified a novel lncRNA
      that was upregulated in adult hearts (Genesymbol NONHSAG000971/NONHSAT002258 or
      ENST00000497710.5), which was a splice variant of the AZIN2 gene (AZIN2-sv). We
      used quantitative PCR to confirm the increased expression of AZIN2-sv in adult
      rat hearts. Coexpression network analysis indicated that AZIN2-sv could regulate
      proliferation. Loss- and gain-of-function approaches demonstrated that AZIN2-sv
      negatively regulated endogenous cardiomyocyte proliferation in vitro and in vivo.
      Knockdown of AZIN2-sv attenuated ventricular remodelling and improved cardiac
      function after myocardial infarction. Phosphatase and tensin homolog (PTEN) was
      identified as a target of AZIN2-sv, their direct binding increased PTEN
      stability. Furthermore, AZIN2-sv acted as a microRNA-214 sponge to release PTEN,
      which blocked activation of the PI3 kinase/Akt pathway to inhibit cardiomyocyte
      proliferation. Conclusions: The newly discovered AZIN2-sv suppressed endogenous
      cardiac regeneration by targeting the PTEN/Akt pathway. Thus, AZIN2-sv may be a
      novel therapeutic target for preventing and treating heart failure.

PMID- 29584822
TI  - Table and Figure Errors.

PMID- 29584821
TI  - Papillary muscles contribute significantly more to left ventricular work in
      dilated hearts.
AB  - Aims: Left ventricular (LV) dilatation results in increased sphericity and
      affects position and orientation of papillary muscles (PMs), which may influence
      their performed work. The aim of this study was to assess the contribution of PM
      to LV function and its changes with dilatation. Methods and results: Fifteen
      sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm)
      pacing, inducing LV dilatation. Five animals served as controls. High-resolution
      gated computed tomography was performed to assess LV volumes, left ventricular
      ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and
      PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron
      emission tomography (PET) was used to measure glucose metabolism as surrogate of
      regional myocardial work. Spatial resolution of PET images was maximized by
      electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was
      measured in PM and compared with remaining left ventricular myocardium (MYO) to
      obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left
      ventricle, with reduced LVEF (P < 0.0001) and GLS (P < 0.0001). In dilated
      hearts, PET analysis revealed a higher contribution of both PM to LV myocardial
      work (P < 0.0001); and PM angle towards LV wall correlated with PM work, together
      with PM width and the LV sphericity index. Sphericity index and posterior PM
      angle were strongest determinants of posterior PM/MYO ratio (R2 = 0.754; P <
      0.0001), while anterior PM/MYO was mostly determined by sphericity index and the
      PM width (R2 = 0.805; P < 0.0001). Conclusion: In dilated hearts, PM contribute
      relatively more to LV myocardial work. We hypothesize that this is caused by the
      more cross-sectional orientation of the subvalvular apparatus, which leads to a
      higher stress on the PM compared with the spherical LV walls. The reduced cross
      sectional area of the PM may further explain their increased stress.

PMID- 29584824
TI  - Infectious Diseases Mortality in the United States: Ongoing Investment Needed for
      Continued Progress.

PMID- 29584823
TI  - Gastroesophageal Reflux Monitoring.

PMID- 29584825
TI  - From Guideline to Order Set to Patient Harm.

PMID- 29584826
TI  - NIH Releases Data from Large Adolescent Brain Study.

PMID- 29584827
TI  - VA Announces Plan to Improve Worst-Performing Medical Centers.

PMID- 29584828
TI  - CMS to Improve Drug Programs and Opioid Overuse Oversight.

PMID- 29584830
TI  - How the Economy Affects Health.

PMID- 29584831
TI  - Legislation for Increased Rank for Medical Officers.

PMID- 29584832
TI  - Three-Year Follow-up of a Trial of Close Contact Casting vs Surgery for Initial
      Treatment of Unstable Ankle Fractures in Older Adults.

PMID- 29584833
TI  - Electronic Health Record Usability Issues and Potential Contribution to Patient
      Harm.

PMID- 29584834
TI  - Genotype vs Clinically Guided Dosing of Warfarin to Prevent Adverse Events.

PMID- 29584835
TI  - Vaccination Strategies During Shortages of Yellow Fever Vaccine.

PMID- 29584836
TI  - Genotype vs Clinically Guided Dosing of Warfarin to Prevent Adverse Events-Reply.

PMID- 29584838
TI  - Similar IVF Birth Rates for Frozen and Fresh Embryos.

PMID- 29584837
TI  - Vaccination Strategies During Shortages of Yellow Fever Vaccine-Reply.

PMID- 29584840
TI  - Benefits of Moderate Physical Activity Despite Frailty.

PMID- 29584839
TI  - Exercise Remodels Heart in Middle Age.

PMID- 29584841
TI  - Brief Psychotherapy for PTSD.

PMID- 29584843
TI  - Trends and Patterns of Differences in Infectious Disease Mortality Among US
      Counties, 1980-2014.
AB  - Importance: Infectious diseases are mostly preventable but still pose a public
      health threat in the United States, where estimates of infectious diseases
      mortality are not available at the county level. Objective: To estimate age
      standardized mortality rates and trends by county from 1980 to 2014 from lower
      respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and
      tuberculosis. Design and Setting: This study used deidentified death records from
      the National Center for Health Statistics (NCHS) and population counts from the
      US Census Bureau, NCHS, and the Human Mortality Database. Validated small-area
      estimation models were applied to these data to estimate county-level infectious
      disease mortality rates. Exposures: County of residence. Main Outcomes and
      Measures: Age-standardized mortality rates of lower respiratory infections,
      diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis by county,
      year, and sex. Results: Between 1980 and 2014, there were 4 081 546 deaths due to
      infectious diseases recorded in the United States. In 2014, a total of 113 650
      (95% uncertainty interval [UI], 108 764-117 942) deaths or a rate of 34.10 (95%
      UI, 32.63-35.38) deaths per 100 000 persons were due to infectious diseases in
      the United States compared to a total of 72 220 (95% UI, 69 887-74 712) deaths or
      a rate of 41.95 (95% UI, 40.52-43.42) deaths per 100 000 persons in 1980, an
      overall decrease of 18.73% (95% UI, 14.95%-23.33%). Lower respiratory infections
      were the leading cause of infectious diseases mortality in 2014 accounting for
      26.87 (95% UI, 25.79-28.05) deaths per 100 000 persons (78.80% of total
      infectious diseases deaths). There were substantial differences among counties in
      death rates from all infectious diseases. Lower respiratory infection had the
      largest absolute mortality inequality among counties (difference between the 10th
      and 90th percentile of the distribution, 24.5 deaths per 100 000 persons).
      However, HIV/AIDS had the highest relative mortality inequality between counties
      (10.0 as the ratio of mortality rate in the 90th and 10th percentile of the
      distribution). Mortality from meningitis and tuberculosis decreased over the
      study period in all US counties. However, diarrheal diseases were the only cause
      of infectious diseases mortality to increase from 2000 to 2014, reaching a rate
      of 2.41 (95% UI, 0.86-2.67) deaths per 100 000 persons, with many counties of
      high mortality extending from Missouri to the northeastern region of the United
      States. Conclusions and Relevance: Between 1980 and 2014, there were declines in
      mortality from most categories of infectious diseases, with large differences
      among US counties. However, over this time there was an increase in mortality for
      diarrheal diseases.

PMID- 29584844
TI  - Hypothermia.

PMID- 29584842
TI  - Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure
      of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A
      Systematic Review and Meta-analysis.
AB  - Importance: Despite increasing emphasis on conservative management of patent
      ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic
      interventions are used to treat those developing a hemodynamically significant
      PDA. Objectives: To estimate the relative likelihood of hemodynamically
      significant PDA closure with common pharmacotherapeutic interventions and to
      compare adverse event rates. Data Sources and Study Selection: The databases of
      MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were
      searched from inception until August 15, 2015, and updated on December 31, 2017,
      along with conference proceedings up to December 2017. Randomized clinical trials
      that enrolled preterm infants with a gestational age younger than 37 weeks
      treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs
      each other, placebo, or no treatment for a clinically or echocardiographically
      diagnosed hemodynamically significant PDA. Data Extraction and Synthesis: Data
      were independently extracted in pairs by 6 reviewers and synthesized with
      Bayesian random-effects network meta-analyses. Main Outcomes and Measures:
      Primary outcome: hemodynamically significant PDA closure; secondary: included
      surgical closure, mortality, necrotizing enterocolitis, and intraventricular
      hemorrhage. Results: In 68 randomized clinical trials of 4802 infants, 14
      different variations of indomethacin, ibuprofen, or acetaminophen were used as
      treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256
      infants). A high dose of oral ibuprofen was associated with a significantly
      higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds
      ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk
      difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of
      intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk
      difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking
      statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic
      option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve,
      0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD,
      0.08]). There was no significant difference in the odds of mortality, necrotizing
      enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment
      compared with any of the other treatment modalities. Conclusions and Relevance: A
      high dose of oral ibuprofen was associated with a higher likelihood of
      hemodynamically significant PDA closure vs standard doses of intravenous
      ibuprofen or intravenous indomethacin; placebo or no treatment did not
      significantly change the likelihood of mortality, necrotizing enterocolitis, or
      intraventricular hemorrhage. Trial Registration: PROSPERO Identifier:
      CRD42015015797.

PMID- 29584845
TI  - beta-Blockers in Myocardial Infarction: Issues With Standard Admission Order
      Sets.

PMID- 29584847
TI  - Mentoring in the Era of #MeToo.

PMID- 29584848
TI  - HIV Preexposure Prophylaxis: A Review.
AB  - Importance: About 40 000 Americans and 2 million people worldwide are newly
      infected with HIV each year. The combination antiretroviral regimen, tenofovir
      disoproxil fumarate (TDF)/emtricitabine, taken as a single pill once daily, has
      been shown to prevent HIV transmission but is used by fewer than 20% of people
      who could benefit in the United States. Observations: PubMed was searched on
      February 15, 2018, using the search terms pre-exposure, prophylaxis, HIV, and
      PrEP to identify English-language articles published between 2010 and 2018. Four
      placebo-controlled randomized clinical trials have demonstrated that preexposure
      prophylaxis (PrEP) with daily dosing of TDF/emtricitabine significantly reduces
      HIV acquisition in men who have sex with men, high-risk heterosexuals, and
      injection drug users who share injection equipment. The efficacy of daily
      TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence.
      TDF/emtricitabine is safe and well-tolerated. Only 2% of people discontinue PrEP
      because of adverse effects. Sexually transmitted infections are common among
      those using PrEP. Resistance to TDF/emtricitabine when used for PrEP is rare
      (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals
      with undiagnosed acute HIV infection who have false-negative findings on HIV
      antibody/antigen testing due to HIV infection acquired within 7 to 10 days of
      testing. Effective methods are needed to identify individuals at high risk for
      acquiring HIV, ensure their access to PrEP, and maximize medication adherence.
      Conclusions and Relevance: TDF/emtricitabine is an effective and safe therapy for
      preventing HIV transmission. Increasing prescription of TDF/emtricitabine for
      patients at risk of acquiring HIV has the potential to reduce new HIV infections.

PMID- 29584851
TI  - Drug-Resistant Infections from Raw Milk.

PMID- 29584850
TI  - A Path to Sustain Rural Hospitals.

PMID- 29584852
TI  - Global Outbreaks Threaten US Economy.

PMID- 29584853
TI  - The importance of a comprehensive evaluation of survivors of cardiac arrest.

PMID- 29584854
TI  - Reoperative sternotomy is associated with primary graft dysfunction following
      heart transplantation.
AB  - OBJECTIVES: Prior sternotomy is associated with increased morbidity and mortality
      following heart transplantation. However, its effect on primary graft dysfunction
      (PGD), a major contributor to early mortality, is unknown. Herein, this effect is
      studied using the International Society for Heart and Lung Transplantation
      consensus definition for PGD. METHODS: Medical records of consecutive adult
      cardiac transplants between 2012 and 2016 were reviewed. Baseline
      characteristics, postoperative findings and 1-year survival were compared between
      patients with and without prior sternotomy. RESULTS: Among 255 total patients
      included, 139 (55%) had undergone prior sternotomy; these recipients were older,
      more often male, had higher body mass index, higher frequencies of united network
      for organ sharing (UNOS) 1A status and ischaemic cardiomyopathy and experienced
      longer waitlist times when compared with those without prior sternotomy (all P <
      0.018). Postoperatively, the prior sternotomy group exhibited higher rates of
      mild to severe PGD (32% vs 18%; P = 0.015) and higher short-term mortality (P =
      0.017) and 1-year mortality (P = 0.047). They required more blood transfusions,
      had more postoperative pneumonia, wound infection and longer hospital stays. A
      stepwise multivariable regression model identified prior sternotomy as a
      predictor of PGD (odds ratio 2.7). Multiple prior sternotomies was associated
      with even more UNOS 1A status, ischaemic cardiomyopathy and pneumonia. However,
      logistic modelling did not show a difference in the rate of PGD between those
      with 1 or >=2 prior sternotomies. CONCLUSIONS: Our data suggest that prior
      sternotomy is a risk factor for PGD. Consistent with previous reports, prior
      sternotomy is associated with increased morbidity, blood product utilization and
      1-year mortality following cardiac transplantation.

PMID- 29584855
TI  - Outcomes of the Warden procedure for partial anomalous pulmonary venous drainage
      in children.
AB  - OBJECTIVES: When drainage of an anomalous pulmonary vein is high into the
      superior vena cava (SVC), traditional techniques of 1-patch or 2-patch repair may
      be challenging. The cavoatrial anastomosis technique (the Warden procedure) was
      developed to reduce the risk of sinus node dysfunction and SVC obstruction.
      Herein, we describe the outcomes of the Warden procedure in children at a single
      institution. METHODS: A retrospective study was conducted on all children with
      partial anomalous pulmonary venous drainage (PAPVD) undergoing the Warden
      procedure from 1996 to 2015. RESULTS: There were 42 PAPVD patients with a right
      upper pulmonary vein entering into the SVC undergoing the Warden procedure. The
      mean age of the patients at surgery was 5.5 years (71 days to 15.4 years). There
      was no operative mortality. Median hospital stay was 5 (3-25) days. One (2.4%)
      patient developed cavoatrial (SVC) obstruction. This patient required
      percutaneous intervention (stenting and balloon dilatation). There was 1 (2.4%)
      late death in a patient with PAPVD and pulmonary atresia due to a hypoxic brain
      injury following catheter intervention for a stenotic conduit. Survival was 97 +/
      3% (95% confidence interval 83-100%) at 5 and 7 years. All patients were
      asymptomatic at a mean follow-up of 6 years (range 1 month to 21 years) after
      surgery. No patient had sick sinus syndrome, sinus node dysfunction or required
      permanent pacemaker at follow-up. CONCLUSIONS: The Warden procedure for repair of
      PAPVD to the SVC can be performed with no operative mortality or permanent
      pacemaker requirement. Mid-term outcomes are excellent with a low occurrence of
      SVC obstruction.

PMID- 29584856
TI  - Oral doxycycline for syphilitic uveitis: a case report highlighting potential
      efficacy.

PMID- 29584858
TI  - Incidence and factors associated with infective endocarditis in patients
      undergoing left-sided heart valve replacement.
AB  - Aims: Patients with left-sided heart valve replacement are considered at high
      risk of infective endocarditis (IE). However, data on the incidence and risk
      factors associated with IE are sparse. Methods and results: Through Danish
      administrative registries, we identified patients who underwent left-sided heart
      valve replacement from January 1996 to December 2015. Patients were categorized
      in mitral and aortic valve replacement (MVR and AVR) and followed until: 12 years
      after valve surgery, end of study, death, emigration, or hospitalization due to
      IE, whichever came first. Multivariable adjusted Cox proportional hazard analysis
      was used to investigate which baseline characteristics were associated with IE. A
      total of 18 041 patients were included. The cumulative IE risk at 10 years follow
      up was 5.2% in both MVR and AVR patients. In patients with MVR, male sex [hazard
      ratio (HR) = 1.68, 95% confidence interval (95% CI) 1.06-2.68], bioprosthetic
      valve (HR = 1.91, 95% CI 1.08-3.37), and heart failure (HR = 1.69, 95% CI 1.06
      2.68) were among factors associated with an increased risk of IE. In AVR
      patients, male sex (HR = 1.59, 95% CI 1.33-1.89), bioprosthetic valve (HR = 1.70,
      95% CI 1.35-2.15), and cardiac implantable electronic device (CIED) (HR = 1.57,
      95% CI 1.19-2.06) were among factors associated with an increased risk of IE.
      Conclusion: Infective endocarditis after left-sided heart valve replacement is
      not uncommon and occurs in about 1/20 over 10 years. Male, bioprosthetic valve,
      and heart failure were among factors associated with IE in MVR patients while
      male, bioprosthetic valve, and CIED were among factors associated with IE in AVR
      patients.

PMID- 29584857
TI  - Impaired Muscle Efficiency but Preserved Peripheral Hemodynamics and
      Mitochondrial Function With Advancing Age: Evidence From Exercise in the Young,
      Old, and Oldest-Old.
AB  - Muscle weakness in the elderly has been linked to recurrent falls and morbidity;
      therefore, elucidating the mechanisms contributing to the loss of muscle function
      and mobility with advancing age is critical. To this aim, we comprehensively
      examined skeletal muscle metabolic function and hemodynamics in 11 young (23 +/-
      2 years), 11 old (68 +/- 2 years), and 10 oldest-old (84 +/- 2 years) physical
      activity-matched participants. Specifically, oxidative stress markers,
      mitochondrial function, and the ATP cost of contraction as well as peripheral
      hemodynamics were assessed during dynamic plantar flexion exercise at 40 per cent
      of maximal work rate (WRmax). Both the PCr recovery time constant and the peak
      rate of mitochondrial ATP synthesis were not significantly different between
      groups. In contrast, the ATP cost of dynamic contractions (young: 1.5 +/- 1.0,
      old: 3.4 +/- 2.1, oldest-old: 6.1 +/- 3.6 mM min-1 W-1) and systemic markers of
      oxidative stress were signficantly increased with age, with the ATP cost of
      contraction being negatively correlated with WRmax (r = .59, p < .05). End-of
      exercise blood flow per Watt rose significantly with increasing age (young: 37 +/
      20, old: 82 +/- 68, oldest-old: 154 +/- 93 mL min-1 W-1). These findings suggest
      that the progressive deterioration of muscle contractile efficiency with
      advancing age may play an important role in the decline in skeletal muscle
      functional capacity in the elderly.

PMID- 29584859
TI  - Loss-of-function mutations in FGF8 can be independent risk factors for
      holoprosencephaly.
AB  - The utilization of next generation sequencing has been shown to accelerate gene
      discovery in human disease. However, our confidence in the correct disease
      associations of rare variants continues to depend on functional analysis. Here,
      we employ a sensitive assay of human FGF8 variants in zebrafish to demonstrate
      that the spectrum of isoforms of FGF8 produced by alternative splicing can
      provide key insights into the genetic susceptibility to human malformations. In
      addition, we describe novel mutations in the FGF core structure that have both
      subtle and profound effects on ligand posttranslational processing and biological
      activity. Finally, we solve a case of apparent digenic inheritance of novel
      variants in SHH and FGF8, two genes known to functionally coregulate each other
      in the developing forebrain, as a simpler case of FGF8 diminished function.

PMID- 29584860
TI  - Substance Use During Imprisonment in Low- and Middle-Income Countries.
AB  - Substance use disorders are among the most common health problems of people
      involved with the criminal justice system. Scaling up addiction services in
      prisons is a global public health and human rights challenge, especially in
      poorly resourced countries. We systematically reviewed the prevalence of
      substance use in prison populations in low- and middle-income countries. We
      searched for studies reporting prevalence rates of nicotine, alcohol, illicit
      drug, and injection drug use during imprisonment in unselected samples of
      imprisoned people in low- and middle-income countries. Data meta-analysis was
      conducted and sources of heterogeneity were examined by meta-regression.
      Prevalence of nicotine use during imprisonment ranged from 5% to 87%, with a
      random-effects pooled estimate of 56% (95% confidence interval (CI): 45, 66) with
      significant geographical heterogeneity. Alcohol use varied from 1% to 76% (pooled
      prevalence, 16%, 95% CI: 9, 25). Approximately one-quarter of people (25%; 95%
      CI: 17, 33; range, 0-78) used illicit drugs during imprisonment. The prevalence
      of injection drug use varied from 0% to 26% (pooled estimate, 1.6%, 95% CI: 0.8,
      3.0). Lifetime substance use was investigated in secondary analyses. The high
      prevalence of smoking in prison suggests that policies regarding smoking need
      careful review. Furthermore, the findings underscore the importance of timely,
      scalable, and available treatments for alcohol and illegal drug use by people
      involved with the criminal justice system.

PMID- 29584861
TI  - Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and
      Monte Carlo simulation.
AB  - Objectives: The oxazolidinone linezolid is an effective component of drug
      resistant TB treatment, but its use is limited by toxicity and the optimum dose
      is uncertain. Current strategies are not informed by clinical pharmacokinetic
      (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods: We defined
      linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119 mg/L/h) and safety (fCmin
      <1.38 mg/L). We extracted individual-level linezolid PK data from existing
      studies on TB patients and performed meta-analysis, producing summary estimates
      of fAUC0-24 and fCmin for published doses. Combining these with a published MIC
      distribution, we performed Monte Carlo simulations of target attainment. Results:
      The efficacy target was attained in all simulated individuals at 300 mg q12h and
      600 mg q12h, but only 20.7% missed the safety target at 300 mg q12h versus 98.5%
      at 600 mg q12h. Although suggesting 300 mg q12h should be used preferentially,
      these data were reliant on a single centre. Efficacy and safety targets were
      missed by 41.0% and 24.2%, respectively, at 300 mg q24h and by 44.6% and 27.5%,
      respectively, at 600 mg q24h. However, the confounding effect of between-study
      heterogeneity on target attainment for q24h regimens was considerable.
      Conclusions: Linezolid dosing at 300 mg q12h may retain the efficacy of the 600
      mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300
      mg q24h and 600 mg q24h doses are limited. Comprehensive, prospectively obtained
      PK/PD data for linezolid doses in drug-resistant TB treatment are required.

PMID- 29584862
TI  - Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled
      analysis of 12 case-control studies.

PMID- 29584863
TI  - Japanese anti- versus pro-influenza vaccination websites: a text-mining analysis.
AB  - Anti-vaccination sentiment exists worldwide and Japan is no exception. Health
      professionals publish pro-influenza vaccination messages online to encourage
      proactive seeking of influenza vaccination. However, influenza vaccine coverage
      among the Japanese population is less than optimal. The contents of pro- and anti
      influenza vaccination websites may contribute to readers' acceptance of one or
      the other position. We aimed to use a text-mining method to examine frequently
      appearing content on websites for and against influenza vaccination. We conducted
      online searches in January 2017 using two major Japanese search engines (Google
      Japan and Yahoo! Japan). Targeted websites were classified as 'pro', 'anti' or
      'neutral' depending on their claims, with author(s) classified as 'health
      professionals', 'mass media' or 'laypersons'. Text-mining analysis was conducted,
      and statistical analysis was performed using a chi-squared test. Of the 334
      websites analyzed, 13 content topics were identified. The three most frequently
      appearing content topics on pro-vaccination websites were vaccination effect for
      preventing serious cases of influenza, side effects of vaccination, and efficacy
      rate of vaccination. The three most frequent topics on anti-vaccination websites
      were ineffectiveness of influenza vaccination, toxicity of vaccination, and side
      effects of vaccination. The main disseminators of each topic, by author
      classification, were also revealed. We discuss possible tactics of online
      influenza vaccination promotion to counter anti-vaccination websites.

PMID- 29584864
TI  - Risk of infective endocarditis after left-sided surgical valve replacement.

PMID- 29584865
TI  - The Admission of Older People Into Residential Care Homes in Argentina: Coercion
      and Human Rights Abuse.
AB  - Background and Objectives: There is very little information about the
      appropriateness of procedures for admitting older people into care homes in low
      and middle-income countries like Argentina. This study provides the first
      systematic study of practice and assesses the extent to which current practice
      respects fundamental human rights. Research Design and Methods: We apply
      different methods, including document review and national survey analysis. The
      study also includes a case study of a single city, La Plata, which draws on local
      key informant interviews, focus group discussions in different neighborhoods, and
      a clandestine surrogate patient survey led by local pensioners. This innovative
      design provides a highly triangulated and contextualized data set. Results: Many
      older people admitted to care homes did not have high levels of care dependency.
      Care homes did not usually require or even seek the informed consent of older
      people, regardless of their cognitive status. There were indications of coercive
      admission by family members, sometimes in order to obtain access to older
      people's homes and other property and finances. Discussion and Implications: The
      study indicates the widespread abuse of the fundamental human rights of tens of
      thousands of older people in Argentina. There is a need for researchers, policy
      makers, and civil society to acknowledge the scale of abuse and develop
      safeguards.

PMID- 29584866
TI  - Levels of serum brain-derived neurotropic factor in individuals at ultra-high
      risk for psychosis - Findings from the Longitudinal Youth at Risk Study (LYRIKS).
AB  - Background: Identifying biomarkers to enrich prognostication and risk predictions
      in individuals at high risk of developing psychosis will enable stratified early
      intervention efforts. Brain-derived neurotrophic factor (BDNF) has been widely
      studied in schizophrenia and in first-episode psychosis with promising results.
      The aim of this study was to examine the levels of serum BDNF between healthy
      controls and individuals with ultra-high risk of psychosis (UHR). Methods: A
      sample of 106 healthy controls and 105 UHR individuals from the Longitudinal
      Youth at Risk Study was included in this study. UHR status was determined using
      the Comprehensive Assessment of At-Risk Mental State (CAARMS) at recruitment.
      Calgary Depression Scale for Schizophrenia (CDSS) was used to assess the severity
      of depression. All participants were followed up over 2 years and UHR remitters
      were defined by UHR individuals who no longer fulfilled CAARMS criteria at the
      end of the study period. Levels of BDNF were measured in the serum by enzyme
      linked immunosorbent assay method (ELISA). Results: The UHR group had
      significantly higher baseline levels of serum BDNF compared with control group
      (3.7 vs. 3.3 ng/ml, p=0.018). However, baseline levels of serum BDNF did not
      predict the development of psychosis (OR=0.64, CI = 0.40 - 1.02) or remission
      (OR=0.83, CI = 0.60 - 1.15) from UHR status. Conclusion: Findings from our study
      did not support a role for serum BDNF in predicting outcomes in UHR individuals.
      However, the finding of higher levels of serum BDNF in UHR individuals deserves
      further study.

PMID- 29584867
TI  - Magnetic resonance microscopy diffusion tensor imaging of collagen fibre bundles
      stabilizing an atherosclerotic plaque of the common carotid artery.

PMID- 29584868
TI  - Antiretroviral Therapy and Mortality in Rural South Africa: A Comparison of
      Causal Modeling Approaches.
AB  - Estimation of causal effects from observational data is a primary goal of
      epidemiology. The use of multiple methods with different assumptions relating to
      exchangeability improves causal inference by demonstrating robustness across
      assumptions. We estimate the effect of antiretroviral therapy (ART) on mortality
      in rural KwaZulu-Natal, South Africa from 2007-2011 using two methods with
      substantially different assumptions: the regression discontinuity design (RDD),
      and inverse probability weighting of marginal structural models (IPW). The RDD
      analysis took advantage of a CD4 count-based threshold for ART initiation (200
      cells/MUl). The two methods yielded consistent but non-identical results for the
      effect of immediate initiation of ART (RDD intention-to-treat hazards ratio (HR)
      0.66, 95% CI 0.35 to 1.26; RDD HR 0.56, 95% CI 0.41 to 0.77; IPW HR 0.49, 95% CI
      0.42 to 0.58). Although RDD and IPW estimates had distinct identifying
      assumptions, strengths, and limitations in terms of internal and external
      validity, results in this application were similar. The differences in modeling
      approaches and external validity of each method may explain the minor differences
      in effect estimates, but the consistency of the results lends support for causal
      inference of the effect of ART and mortality from these data.

PMID- 29584870
TI  - Understanding Human-Derived Antibodies Generated by Polymorphic Malaria Vaccine
      Against Merozoite Surface Protein 2.

PMID- 29584869
TI  - The Health of America's Aging Prison Population.
AB  - Older incarcerated individuals comprise the fastest growing demographic in the US
      prison system. Unhealthy lifestyles among incarcerated individuals and inadequate
      health care lead to earlier onset and more rapid progression of many chronic
      conditions that are prevalent among community-living older adults. There are
      limited peer-reviewed epidemiologic data in this area; however, there is growing
      interest in identifying strategies for housing aging incarcerated individuals,
      delivering appropriate health care in prisons, and coordinating after-release
      health care. In this systematic review, we summarize the epidemiologic evidence
      of the health challenges facing the aging US prison population. Our comprehensive
      literature search focused on health outcomes, including diseases, comorbid
      conditions, mental health, cognition, and mobility. From 12,486 articles
      identified from the literature search, we reviewed 21 studies published between
      2007 and 2017. All the studies were observational and cross-sectional, and most
      (n = 17) were based on regional samples. Sample sizes varied widely, ranging from
      25 to 14,499 incarcerated people (median, 258). In general, compared with their
      younger counterparts, older incarcerated individuals reported high rates of
      diabetes mellitus, cardiovascular conditions, and liver disease. Mental health
      problems were common, especially anxiety, fear of desire for death or suicide,
      and depression. Activities of daily living were challenging for up to one-fifth
      of the population. We found no empirical data on cognition among older
      incarcerated individuals. The findings of this review reveal few empirical data
      in this area and highlight the need for new data to drive policy and practice
      patterns that address critical health issues related to the aging prison
      population.

PMID- 29584871
TI  - Religious Communities, Health, and Well-Being - Address to the US Air Force
      Chaplain.
AB  - The text is adapted from a written transcript of the address to the US Air Force
      Chaplain Corps Summit, delivered by Tyler J. VanderWeele, on March 28, 2017 in
      San Antonio, Texas. The address discussed rigorous empirical research on how
      religious participation and religious community are related to a number of health
      and well-being outcomes, along with the mechanisms behind these associations, and
      the implications of such religion health research to military chaplains, and to
      society more broadly.

PMID- 29584873
TI  - RE: "BEST PRACTICES FOR GAUGING EVIDENCE OF CAUSALITY IN AIR POLLUTION
      EPIDEMIOLOGY".

PMID- 29584872
TI  - Sliding of a single lac repressor protein along DNA is tuned by DNA sequence and
      molecular switching.
AB  - In any living cell, genome maintenance is carried out by DNA-binding proteins
      that recognize specific sequences among a vast amount of DNA. This includes
      fundamental processes such as DNA replication, DNA repair, and gene expression
      and regulation. Here, we study the mechanism of DNA target search by a single lac
      repressor protein (LacI) with ultrafast force-clamp spectroscopy, a sub
      millisecond and few base-pair resolution technique based on laser tweezers. We
      measure 1D-diffusion of proteins on DNA at physiological salt concentrations with
      20 bp resolution and find that sliding of LacI along DNA is sequence dependent.
      We show that only allosterically activated LacI slides along non-specific DNA
      sequences during target search, whereas the inhibited conformation does not
      support sliding and weakly interacts with DNA. Moreover, we find that LacI
      undergoes a load-dependent conformational change when it switches between sliding
      and strong binding to the target sequence. Our data reveal how DNA sequence and
      molecular switching regulate LacI target search process and provide a
      comprehensive model of facilitated diffusion for LacI.

PMID- 29584874
TI  - Secondhand Smoke Exposure among High Risk Patients in The U.S. (NHANES 2001
      2012): Implications for Clinical Practice.
AB  - Introduction: Patients with cancer, cardiovascular disease (CVD), and respiratory
      disease are susceptible to health consequences related to secondhand smoke (SHS)
      exposure. The current study examined the prevalence, time-trends and correlates
      of SHS exposure among these patients compared to individuals without these
      diseases (control). Methods: Data were obtained from the 2001-2012 National
      Health and Nutrition Examination Survey. All adults (>20 years old), who were
      nonsmokers and exposed to SHS (serum cotinine level 0.015-10 ng/mL), had cancer
      (n=1,440), CVD (congestive heart failure, coronary heart disease, angina, heart
      attack, or stroke; n=1,754), respiratory disease (asthma, chronic bronchitis,
      emphysema; n=1,444), or none of these diseases (control; n=11,615) were included
      in the analysis. Weighted prevalence, weighted second degree polynomial linear
      regression of prevalence on year for trend analysis, and multivariable logistic
      regression analyses were performed with adjustments to the complex survey design.
      Results: SHS exposure was the highest among patients with respiratory disease
      (72.1%), followed by CVD (70.6%), controls (70.4%) and cancer patients (65.4%).
      From 2001 to 2012, exposure decreased the most among CVD patients (19.6%),
      followed by controls (16.0%), cancer patients (14.7%), and respiratory patients
      (10.0%). Exposed individuals in all groups were more likely to be younger, Black,
      and less educated. Exposed patients with respiratory disease were more likely to
      be former smokers (P <.05 for all). Conclusions: SHS exposure among these
      patients is high and comparable to the general population. Strengthening smoke
      free polices in all settings is critical. More efforts are needed to address SHS
      exposure more effectively in clinical care settings. Implications: Despite the
      negative health effect of SHS exposure among patients with cancer, CVD and
      respiratory disease, modest progress has been made in reducing their exposure.
      Continued efforts to strengthen smoke-free polices in workplaces, public place,
      and multi-unit housing is critical. In addition, exposure to SHS among these
      patients seems to be overlooked in clinical care settings. More efforts are
      needed to address this problem more effectively in healthcare settings and
      investigate specific interventions directed at increasing patients' awareness
      about the risk of exposure to SHS and helping them reducing their exposure.

PMID- 29584875
TI  - Urine and Serum Sex Steroid Profile in Testosterone-Treated Transgender and
      Hypogonadal and Healthy Control Men.
AB  - Background: The impact of testosterone (T) treatment on antidoping detection
      tests in female-to-male (F2M) transgender men is unknown. We investigated urine
      and serum sex steroid and luteinizing hormone (LH) profiles in T-treated F2M men
      to determine whether and, if so, how they differed from hypogonadal and healthy
      control men. Method: Healthy transgender (n = 23) and hypogonadal (n = 24) men
      aged 18 to 50 years treated with 1000 mg injectable T undecanoate provided trough
      urine and blood samples and an additional earlier postinjection sample (n = 21).
      Healthy control men (n = 20) provided a single blood and urine sample. Steroids
      were measured by mass spectrometry-based methods in urine and serum, LH by
      immunoassay, and uridine 5'-diphospho-glucuronosyltransferase 2B17 genotype by
      polymerase chain reaction. Results: Urine LH, human chorionic gonadotropin, T,
      epitestosterone (EpiT), androsterone (A), etiocholanolone (Etio), A/Etio ratio,
      dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and 5alpha,3alpha- and
      5beta,3alpha-androstanediols did not differ between groups or by time since last
      T injection. Urine T/EpiT ratio was <4 in all controls and 12/68 (18%) samples
      from T-treated men, but there was no difference between T-treated groups. Serum
      estradiol, estrone, and DHEA were higher in transgender men, and serum T and DHT
      were higher in earlier compared with trough blood samples, but serum LH, follicle
      stimulating hormone, and 3alpha- and 3beta,5alpha-diols did not differ between
      groups. Conclusion: Urine antidoping detection tests in T-treated transgender men
      can be interpreted like those of T-treated hypogonadal men and are unaffected by
      time since last T dose. Serum steroids are more sensitive to detect exogenous T
      administration early but not later after the last T dose.

PMID- 29584877
TI  - Erratum.

PMID- 29584876
TI  - Paired D10A Cas9 nickases are sometimes more efficient than individual nucleases
      for gene disruption.
AB  - The use of paired Cas9 nickases instead of Cas9 nuclease drastically reduces off
      target effects. Because both nickases must function for a nickase pair to make a
      double-strand break, the efficiency of paired nickases can intuitively be
      expected to be lower than that of either corresponding nuclease alone. Here, we
      carefully compared the gene-disrupting efficiency of Cas9 paired nickases with
      that of nucleases. Interestingly, the T7E1 assay and deep sequencing showed that
      on-target efficiency of paired D10A Cas9 nickases was frequently comparable, but
      sometimes higher than that of either corresponding nucleases in mammalian cells.
      As the underlying mechanism, we found that the HNH domain, which is preserved in
      the D10A Cas9 nickase, has higher activity than the RuvC domain in mammalian
      cells. In this study, we showed: (i) the in vivo cleavage efficiency of the HNH
      domain of Cas9 in mammalian cells is higher than that of the RuvC domain, (ii)
      paired Cas9 nickases are sometimes more efficient than individual nucleases for
      gene disruption. We envision that our findings which were overlooked in previous
      reports will serve as a new potential guideline for tool selection for CRISPR
      Cas9-mediated gene disruption, facilitating efficient and precise genome editing.

PMID- 29584878
TI  - Increases in Human Papillomavirus Vaccination Among Adolescent and Young Adult
      Males in the United States, 2011-2016.
AB  - In the United States, human papillomavirus (HPV) vaccination has been recommended
      for females since 2006 and males since 2011. We assessed temporal trends in HPV
      vaccine coverage (defined as receipt of >=1 dose) among 9-26-year-old
      participants in the 2011-2016 National Health and Nutrition Examination Surveys.
      While coverage increased overall, from 37.7% to 45.7%, among females (adjusted
      prevalence difference [aPD], 7.1%; 95% confidence interval [CI], .1%-13.7%),
      there was no change among female adolescents aged 9-17 years. For males, coverage
      increased overall, from 7.8% to 27.4% (aPD, 18.8%; 95% CI, 14.1%-23.5%), and
      among every stratum of age, race/ethnicity, health insurance status, poverty
      level, and immigration status (P <= .05). The increase in HPV vaccine coverage
      observed among males is encouraging, but coverage remains below national targets
      for both males and females.

PMID- 29584879
TI  - Loss of RNA-binding protein HuR facilitates cellular senescence through
      posttranscriptional regulation of TIN2 mRNA.
AB  - Cellular senescence can be induced by high levels of reactive oxygen species
      (ROS) produced by mitochondria. However, the mechanism by which elevated
      mitochondrial ROS levels are produced during replicative senescence is not yet
      fully understood. Here, we report that loss of the RNA-binding protein, human
      antigen R (HuR), during replicative senescence leads to an increase in ROS levels
      through enhanced mitochondrial localization of the telomeric protein TIN2. HuR
      binds to the 3' untranslated region of TIN2 mRNA. This association decreases TIN2
      protein levels by both destabilizing TIN2 mRNA and reducing its translation.
      Conversely, depletion of HuR levels enhances TIN2 expression, leading to
      increased mitochondrial targeting of TIN2. Mitochondrial localization of TIN2
      increases ROS levels, which contributes to induction and maintenance of cellular
      senescence. Our findings provide compelling evidence for a novel role of HuR in
      controlling the process of cellular senescence by regulating TIN2-mediated
      mitochondrial ROS production, and for a useful therapeutic route for modulating
      intracellular ROS levels in treating both aging-related complications and cancer.

PMID- 29584880
TI  - Morbidity and housing status 10 years after shelter use-follow-up of homeless men
      in Helsinki, Finland.
AB  - Background: Homelessness is associated with increased mortality, morbidity and
      social difficulties and periods of homelessness are sometimes prolonged or
      repeated. However, there are no long-term follow-up studies focusing upon housing
      status among homeless people. The aim of this study was to examine morbidity and
      housing outcomes and to identify factors predicting being independently housed 10
      years after shelter use. Methods: By combining data from several registers we
      followed all 552 homeless men who stayed in shelter in Helsinki during 2004 and
      determined their housing situation and morbidity 10 years later. Their situation
      was compared with an age-matched control group from the general population (N =
      946). Using logistic regression analysis, we assessed the predictive effects of
      socioeconomic factors and health service use at baseline on becoming
      independently housed. Results: By the end of the follow-up 52.0% of the formerly
      homeless study group had died, compared with 14.6% of the controls. At 10 years,
      6.0% were independently housed, 37.5% lived in supported housing and 4.5% were
      still or again homeless. Psychiatric disorders, including substance use disorder,
      were present in 77.5% of the homeless, compared with 16.1% among the controls.
      Being married (OR 8.3, 95% CI 3.0 to 23.2) and having less than four shelter
      nights in year 2004 (OR 9.1, 95% CI 2.7 to 30.8) strongly predicted being
      independently housed 10 years later. Conclusions: Homeless staying in shelters
      have high mortality and morbidity and most of those surviving, are in need of
      support in their everyday lives even years after the shelter period.

PMID- 29584881
TI  - Erratum.

PMID- 29584885
TI  - Ribavirin Had Demonstrable Effects on the Crimean-Congo Hemorrhagic Fever Virus
      (CCHFV) Population and Load in a Patient With CCHF Infection.
AB  - The use of ribavirin to treat Crimean-Congo hemorrhagic fever virus (CCHFV)
      infection has been controversial, based on uncertainties about its antiviral
      efficacy in clinical case studies. We studied the effect of ribavirin treatment
      on viral populations in a recent case by deep-sequencing analysis of plasma
      samples obtained from a CCHFV-infected patient before, during, and after a 5-day
      regimen of ribavirin treatment. The CCHFV load dropped during ribavirin
      treatment, and subclonal diversity (transitions) and indels increased in viral
      genomes during treatment. Although the results are based on a single case, these
      data demonstrate the mutagenic effect of ribavirin on CCHFV in vivo.

PMID- 29584886
TI  - Effect of Confusing Symptoms and Infectiousness on Forecasting and Control of
      Ebola Outbreaks.

PMID- 29584888
TI  - Estimating Monitoring Trap Plume Reach and Trapping Area for Drosophila suzukii
      (Diptera: Drosophilidae) in Michigan Tart Cherry.
AB  - Central-monitoring trap, multiple point release-recapture experiments were used
      to interpret Drosophila suzukii (Diptera: Drosophilidae) catch in a monitoring
      trap baited with a Scentry Biologicals commercial D. suzukii lure deployed in
      Michigan tart cherry orchards. The plume reach was found to be short (<3 m),
      while the maximum dispersive distance for 95% of the released D. suzukii was
      projected to be ca. 90 m, so as to yield a trapping area of 2.7 ha. These data
      were consistent across two growing seasons and provide the first information
      about the dispersal distance and monitoring trap efficacy in a fruit crop setting
      for D. suzukii. Catch data per single monitoring trap can now be used to estimate
      absolute pest density in cherries. Alarmingly, catching one D. suzukii in a
      monitoring trap translates to approximately 192 D. suzukii per trapping area of
      2.7 ha (26 per acre). Thus, by the time D. suzukii catch becomes detectable, it
      is very probable that the population is already above the tolerable damage
      threshold, suggesting control measures should immediately be taken if the fruit
      is in a vulnerable stage. Caution should be taken when extrapolating these
      results from cherry because the measured values may differ in other crop systems.

PMID- 29584887
TI  - National survey of myeloablative total body irradiation prior to hematopoietic
      stem cell transplantation in Japan: survey of the Japanese Radiation Oncology
      Study Group (JROSG).
AB  - A myeloablative regimen that includes total-body irradiation (TBI) before
      hematopoietic stem cell transplantation results in higher patient survival rates
      than achieved with regimens without TBI. The TBI protocol, however, varies
      between institutions. In October 2015, the Japanese Radiation Oncology Study
      Group initiated a national survey of myeloablative TBI (covering 2010-2014).
      Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82
      institutions that had performed myeloablative TBI during this period treated 2698
      patients with malignant disease [leukemia (2082 patients, 77.2%), malignant
      lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia
      (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used
      at all institutions. The institutions were divided into 41 large and 41 small
      institutions based on the median number of patients. The long source-surface
      distance technique was the method of choice in the 34 institutions (82.9%) and
      the moving-couch technique in the 7 (17.1%) in the large institutions. The
      schedules most routinely used by the participating institutions consisted of 12
      Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The
      dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely
      shielded in 23 large institutions (56.1%), and only the lungs in 9 large
      institutions (21.9%). At lung-shielding institutions, the most frequent maximum
      acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our
      results reveal considerable differences in the TBI methods used by Japanese
      institutions and thus the challenges in designing multicenter randomized trials
      based on TBI.

PMID- 29584889
TI  - Longitudinal Assessment of Illnesses, Stress Dosing, and Illness Sequelae in
      Patients With Congenital Adrenal Hyperplasia.
AB  - Context: Patients with congenital adrenal hyperplasia (CAH) are at risk for life
      threatening adrenal crises. Management of illness episodes aims to prevent
      adrenal crises. Objective: We evaluated rates of illnesses and associated factors
      in patients with CAH followed prospectively and receiving repeated glucocorticoid
      stress dosing education. Methods: Longitudinal analysis of 156 patients with CAH
      followed at the National Institutes of Health Clinical Center over 23 years was
      performed. The rates of illnesses and stress-dose days, emergency room (ER)
      visits, hospitalizations, and adrenal crises were analyzed in relation to
      phenotype, age, sex, treatment, and hormonal evaluations. Results: A total of
      2298 visits were evaluated. Patients were followed for 9.3 +/- 6.0 years. During
      childhood, there were more illness episodes and stress dosing than adulthood (P <
      0.001); however, more ER visits and hospitalizations occurred during adulthood (P
      <= 0.03). The most robust predictors of stress dosing were young age, low
      hydrocortisone and high fludrocortisone dose during childhood, and female sex
      during adulthood. Gastrointestinal and upper respiratory tract infections (URIs)
      were the two most common precipitating events for adrenal crises and
      hospitalizations across all ages. Adrenal crisis with probable hypoglycemia
      occurred in 11 pediatric patients (ages 1.1 to 11.3 years). Undetectable
      epinephrine was associated with ER visits during childhood (P = 0.03) and illness
      episodes during adulthood (P = 0.03). Conclusions: Repeated stress-related
      glucocorticoid dosing teaching is essential, but revised age-appropriate
      guidelines for the management of infectious illnesses are needed for patients
      with adrenal insufficiency that aim to reduce adrenal crises and prevent
      hypoglycemia, particularly in children.

PMID- 29584890
TI  - Effectiveness of an Anger Intervention for Military Members with PTSD: A Clinical
      Case Series.
AB  - Objective: Problematic anger is a significant clinical issue in military
      personnel, and is further complicated by comorbid post-traumatic stress disorder
      (PTSD). Despite increasing numbers of military personnel returning from
      deployment with anger and aggression difficulties, the treatment of problematic
      anger has received scant attention. There are currently no interventions that
      directly target problematic anger in the context of military-related PTSD. The
      aim of this case series is to examine the effectiveness of an intervention
      specifically developed for treating problematic anger in current serving military
      personnel with comorbid PTSD. Methods: Eight Australian Defence Force Army
      personnel with problematic anger and comorbid PTSD received a manualized 12
      session cognitive behaviorally based anger intervention, delivered one-to-one by
      Australian Defence Force mental health clinicians. Standardized measures of
      anger, PTSD, depression, and anxiety were administered pre- and post-treatment.
      Results: The initial mean severity scores for anger indicated a high degree of
      pre-treatment problematic anger. Anger scores reduced significantly from pre to
      post-treatment (d = 1.56), with 88% of participants exhibiting meaningful
      reduction in anger scores. PTSD symptoms also reduced significantly (d= 0.96),
      with 63% of participants experiencing a clinically meaningful reduction in PTSD
      scores. All of those who took part in the therapy completed all therapy sessions.
      Conclusions: This brief report provides preliminary evidence that an intervention
      for problematic anger not only significantly reduces anger levels in military
      personnel, but can also significantly reduce PTSD symptoms. Given that anger can
      interfere with PTSD treatment outcomes, prioritizing anger treatment may improve
      the effectiveness of PTSD interventions.

PMID- 29584891
TI  - Unveiling the pathway to Z-DNA in the protein-induced B-Z transition.
AB  - Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by
      special sequences under specific biological, chemical or physical conditions.
      Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high
      affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences
      embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1
      bound DNA conformations in both GC and TG repeat sequences. Based on a
      statistical physics model, we determined quantitatively the affinities of ADAR1
      to both Z-form and B-form of these sequences. We also reported what pathways it
      takes to induce the B-Z transition in those sequences. Due to the high junction
      energy, an intermediate B* state has to accumulate prior to the B-Z transition.
      Our study showing the stable B* state supports the active picture for the protein
      induced B-Z transition that occurs under a physiological setting.

PMID- 29584892
TI  - AN AUTHOR REPLIES.

PMID- 29584893
TI  - Increase in Childhood Nontuberculous Mycobacterial Infections After Bacille
      Calmette-Guerin Coverage Drop: A Nationwide, Population-Based Retrospective
      Study, Finland, 1995-2016.
AB  - Background: Epidemiological data on childhood nontuberculous mycobacterial (NTM)
      disease is scarce and the protective effect of bacille Calmette-Guerin (BCG)
      vaccination remains debated. In 2006, the BCG policy in Finland changed from
      universal to selective. We aimed to study the effect of the BCG coverage decrease
      on the incidence of childhood NTM infections in Finland. Methods: We conducted a
      nationwide, population-based, retrospective study of NTM notifications recorded
      to the National Infectious Diseases Register between 1995 and 2016 and identified
      native-born children aged 0-4 years infected with NTM. Poisson log-linear model
      was used to estimate the change in the incidence rate of cohorts born during
      universal or selective BCG policy between 1995 and 2015. Results: We identified
      97 native-born children aged <5 years infected with NTM (median age, 27 months;
      female-to-male ratio, 2:1). The most common species was Mycobacterium avium (n =
      69 [71%]). The estimated incidence rates of NTM in universal-BCG and selective
      BCG cohorts were 0.2 and 3.9 per 100000 person-years, respectively. The incidence
      rate ratio of selective-BCG cohorts compared to universal-BCG cohorts was 19.03
      (95% confidence interval, 8.82-41.07; P < .001). Conclusions: After infant BCG
      coverage in Finland decreased, childhood NTM infections increased drastically. As
      there is no other apparent cause for the increase, this indicates that BCG offers
      protection against childhood NTM disease. This observation adds to the
      understanding of childhood NTM epidemiology and might explain why the disease is
      emerging in some countries.

PMID- 29584894
TI  - Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.
AB  - Context: Tight glycemic control throughout pregnancy in women with type 1
      diabetes is crucial, and knowledge about which factors that affect insulin
      sensitivity could improve the outcome for both mother and offspring. Objective:
      To evaluate insulin requirements in women with type 1 diabetes during pregnancy
      and test whether parity affects insulin requirements. Design: Observational
      cohort study consisting of women with type 1 diabetes who gave birth at Aarhus
      University Hospital, Denmark, from 2004 to 2014. Main Outcome Measure: Daily
      insulin requirement (the hypothesis that parity could affect insulin resistance
      was formulated before data collection). Results: A total of 380 women with a
      total of 536 pregnancies were included in the study. Mean age was 31.1 years, and
      prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1,
      40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased
      significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of
      70% (P < 0.0005) at weeks 33 to 36. Overall, insulin requirements increased
      significantly with parity. The unadjusted differences between P0 and P1, P2, and
      P3+4 were 9% (P < 0.0005), 12% (P < 0.0005), and 23% (P < 0.0011), respectively.
      After adjustment for confounders, differences were 13% (P < 0.0005), 20% (P <
      0.0005), and 36% (P < 0.0005). We also observed an adjusted difference between P1
      and P3+4 of 20% (P < 0.0012). Conclusions: The data show changes in insulin
      requirements from week to week in pregnancy and indicate that insulin
      requirements increase with parity. This suggests that the patient's parity
      probably should be considered in choosing insulin dosages for pregnant women with
      type 1 diabetes.

PMID- 29584895
TI  - Reducing falls in older adults recently discharged from hospital: a systematic
      review and meta-analysis.
AB  - Background: older adults are known to have increased falls rates and functional
      decline following hospital discharge, with substantial economic healthcare costs.
      This systematic review aimed to synthesise the evidence for effective falls
      prevention interventions in older adults recently discharged from hospital.
      Methods: literature searches of six databases of quantitative studies conducted
      from 1990 to June 2017, reporting falls outcomes of falls prevention
      interventions for community-dwelling older adults discharged from hospital were
      included. Study quality was assessed using a standardised JBI critical appraisal
      tool (MAStARI) and data pooled using Rev-Man Review Manager(r). Results: sixteen
      studies (total sample size N = 3,290, from eight countries, mean age 77)
      comprising 12 interventions met inclusion criteria. We found home hazard
      modification interventions delivered to those with a previous falls history (1
      study), was effective in reducing the number of falls (RR 0.63, 95%CI 0.43, 0.93,
      Low GRADE evidence). Home exercise interventions (3 studies) significantly
      increased the proportion of fallers (OR 1.74, 95%CI 1.17, 2.60, Moderate GRADE
      evidence), and did not significantly reduce falls rate (RR 1.27, 95%CI 0.99,
      1.62, Very Low GRADE evidence) or falls injury rate (RR 1.16, 95%CI, 0.83,1.63,
      Low GRADE evidence). Nutritional supplementation for malnourished older adults (1
      study) significantly reduced the proportion of fallers (HR 0.41, 95% CI 0.19,
      0.86, Low GRADE evidence). Conclusion: the recommended falls prevention
      interventions for older adults recently discharged from hospital are to provide
      home hazard minimisation particularly if they have a recent previous falls
      history and consider nutritional supplementation if they are malnourished.

PMID- 29584896
TI  - Interactive medical word sense disambiguation through informed learning.
AB  - Objective: Medical word sense disambiguation (WSD) is challenging and often
      requires significant training with data labeled by domain experts. This work aims
      to develop an interactive learning algorithm that makes efficient use of expert's
      domain knowledge in building high-quality medical WSD models with minimal human
      effort. Methods: We developed an interactive learning algorithm with expert
      labeling instances and features. An expert can provide supervision in 3 ways:
      labeling instances, specifying indicative words of a sense, and highlighting
      supporting evidence in a labeled instance. The algorithm learns from these labels
      and iteratively selects the most informative instances to ask for future labels.
      Our evaluation used 3 WSD corpora: 198 ambiguous terms from Medical Subject
      Headings (MSH) as MEDLINE indexing terms, 74 ambiguous abbreviations in clinical
      notes from the University of Minnesota (UMN), and 24 ambiguous abbreviations in
      clinical notes from Vanderbilt University Hospital (VUH). For each ambiguous term
      and each learning algorithm, a learning curve that plots the accuracy on the test
      set against the number of labeled instances was generated. The area under the
      learning curve was used as the primary evaluation metric. Results: Our
      interactive learning algorithm significantly outperformed active learning, the
      previous fastest learning algorithm for medical WSD. Compared to active learning,
      it achieved 90% accuracy for the MSH corpus with 42% less labeling effort, 35%
      less labeling effort for the UMN corpus, and 16% less labeling effort for the VUH
      corpus. Conclusions: High-quality WSD models can be efficiently trained with
      minimal supervision by inviting experts to label informative instances and
      provide domain knowledge through labeling/highlighting contextual features.

PMID- 29584898
TI  - AN ANALYSIS OF OPERATING PHYSICIAN AND PATIENT RADIATION EXPOSURE DURING RADIAL
      CORONARY ANGIOPLASTIES.
AB  - The objective of this study was to evaluate radiation exposure levels in
      conjunction with operator dose implemented, patient vascular characteristics, and
      other technical angiographic parameters. In total, 756 radial coronary
      angioplasties were evaluated in a major metropolitan general hospital in Tabriz,
      Iran. The classification of coronary lesions was based on the ACC/AHA system. One
      interventional cardiologist performed all of the procedures using a single
      angiography unit. The mean kerma-area product and mean cumulative dose for all
      cases was 5081 MUGy m2 and 814.44 mGy, respectively. Average times of 26.16 and
      9.1 min were recorded for the overall procedure and fluoroscopy, respectively. A
      strong correlation was demonstrated between types of lesions, number of stents
      and vessels treated in relation to physician radiation exposure. It was
      determined that operator radiation exposure levels for percutaneous coronary
      interventions lesions (complex) were higher than that of simple and moderate
      lesions. In addition, operator radiation exposure levels increased with the
      treatment of more coronary vessels and implementation of additional stents.

PMID- 29584897
TI  - Magnetic resonance imaging guidance for the optimization of ventricular
      tachycardia ablation.
AB  - Catheter ablation has an important role in the management of patients with
      ventricular tachycardia (VT) but is limited by modest long-term success rates.
      Magnetic resonance imaging (MRI) can provide valuable anatomic and functional
      information as well as potentially improve identification of target sites for
      ablation. A major limitation of current MRI protocols is the spatial resolution
      required to identify the areas of tissue responsible for VT but recent
      developments have led to new strategies which may improve substrate assessment.
      Potential ways in which detailed information gained from MRI may be utilized
      during electrophysiology procedures include image integration or performing a
      procedure under real-time MRI guidance. Image integration allows pre-procedural
      magnetic resonance (MR) images to be registered with electroanatomical maps to
      help guide VT ablation and has shown promise in preliminary studies. However,
      multiple errors can arise during this process due to the registration technique
      used, changes in ventricular geometry between the time of MRI and the ablation
      procedure, respiratory and cardiac motion. As isthmus sites may only be a few
      millimetres wide, reducing these errors may be critical to improve outcomes in VT
      ablation. Real-time MR-guided intervention has emerged as an alternative solution
      to address the limitations of pre-acquired imaging to guide ablation. There is
      now a growing body of literature describing the feasibility, techniques, and
      potential applications of real-time MR-guided electrophysiology. We review
      whether real-time MR-guided intervention could be applied in the setting of VT
      ablation and the potential challenges that need to be overcome.

PMID- 29584899
TI  - Verification and Determination of the Thyroid Peroxidase Antibody Reference
      Interval: Insight Into the CLSI Guideline.
AB  - Objective: To verify the upper reference limit and define the population-based
      reference interval (RI) for thyroid peroxidase antibody, according to Clinical
      and Laboratory Standards Institute (CLSI) guidelines. Material and Methods: We
      subjected serum samples from 146 subjects to thyroid-stimulating hormone (TSH)
      and TPO Ab analysis for verification and determination of RI. We verified an
      upper reference limit for thyroid peroxidase antibody (TPO Ab) and established an
      RI according to National Academy of Clinical Biochemistry (NACB) and CLSI
      guidelines. Results: The manufacturer's suggested upper reference limit was not
      verified for use as a functional reference value. Rather, on defining the RI of
      TPO Ab by means of a full-scale study, we found a higher upper reference limit
      (13.8 vs 12.0). We calculated lower and upper reference limits of 3.3 and 13.8,
      with 90% confidence intervals (CIs) of 2.8 to 3.5 and 13.6 to 14.8, respectively.
      Conclusion: RIs provided by assay manufacturers are general data and may not
      always be appropriate for different locations and patient demographics.
      Verification of an RI is necessary before use in a given patient population.

PMID- 29584900
TI  - Comment on: IgG4-related disease presenting with raised serum IgG2-real timeline
      of IgG4-RD?: reply.

PMID- 29584901
TI  - The 'Conchie Corps': Conflict, Compromise and Conscientious Objection in the
      British Army, 1940-1945.

PMID- 29584902
TI  - OPTIMIZATION OF A RADIOPHOTOLUMINESCENT GLASS DOSEMETER FOR OCCUPATIONAL EYE LENS
      DOSIMETRY IN INTERVENTIONAL RADIOLOGY/CARDIOLOGY.
AB  - Hospital based workers that perform interventional radiology are at risk of
      reaching the eye lens dose limit of 20 mSv/y. These workers are exposed to the
      radiation scattered by the patient, which creates a complex field, with low
      radiation energy reaching the eyes of the medical staff from wide angles.
      Therefore, the dosemeter used in the assessment of the eye lens dose of
      interventional radiologists needs to respond accurately in such conditions. In
      this study, the angular response of a commercially available
      radiophotoluminescent glass dosemeter, GD-352M, was optimized via Monte Carlo
      simulations, aiming at its use as eye lens dosemeter in interventional radiology.
      The improved dosemeter was manufactured and then characterized in terms of Hp(3),
      the quantity recommended for eye lens dosimetry. Its response was compared to the
      IEC 62387:2012 requirements for Hp(3) and to requirements proposed specifically
      for eye lens dosemeters used in interventional radiology. The improved dosemeter
      meets the IEC 62387:2012 requirements for energy and angular response for Hp(3)
      and also shows good agreement with the more strict requisites proposed for eye
      lens dosemeters to be used in interventional radiology.

PMID- 29584903
TI  - Multifaceted Cellular Reprogramming at the Crossroads Between Plant Development
      and Biotic Interactions.

PMID- 29584905
TI  - Effects of production systems on the carcass and meat quality characteristics of
      spent laying hens.
AB  - This study evaluated the carcass characteristics and meat quality attributes of
      spent laying hens raised under conventional battery cage and free-range systems.
      Thirty free-range and 30 conventional battery-caged Lohmann Brown-Elite spent
      laying hens of 53 and 40 wk of age, respectively were obtained from a commercial
      egg producer. Carcass, portion, and organ weights and percentages were
      determined. Physicochemical analyses were performed on thigh and breast meat
      samples. Caged hens had heavier (P <= 0.05) warm and cold carcasses, thighs,
      wings, and feet. The percentages of the breast (26.1 +/- 0.51 vs. 28.3 +/- 0.28),
      drum, breast bones, breast thaw and cooking loss, and thigh cooking loss were
      higher (P <= 0.05) for free-range than for caged hens. Free-range hens had heavy
      (P <= 0.05) gizzards (33.9 +/- 1.04 vs. 30.5 +/- 0.73) and bones and a lower (P
      <= 0.05) breast meat percentage (47.3 +/- 0.94 vs. 51.7 +/- 1.35). Meat redness
      (a*) (0.54 +/- 0.222 vs. 1.40 +/- 0.135) and hue angle, skin redness (a*), breast
      (12.37 +/- 0.411 vs. 17.10 +/- 0.751), and thigh (29.68 +/- 0.306 vs. 39.75 +/-
      0.826) Warner-Bratzler shear force values (N), breast moisture, and thigh ash
      content were higher (P <= 0.05) for free-range hens. Caged hens had a higher (P
      <= 0.05) thigh thaw loss percentage and breast ash content. Production system
      significantly influenced the carcass characteristics and meat quality of spent
      laying hens. The results of this study supply baseline information for the
      utilization of spent laying hens by the poultry industry and consumers.

PMID- 29584904
TI  - Combined Pathologies in FTLD-TDP Types A and C.
AB  - This study investigated the presence of combined pathologies in a large cohort of
      autopsies that show a primary pathologic diagnosis of phosphorylated 43-kDa TAR
      DNA-binding protein (FTLD-TDP), the majority of which portrayed clinical
      phenotypes consistent with primary progressive aphasia or behavioral variant
      frontotemporal dementia (bvFTD). Thirty-eight cases with FTLD-TDP (30 type-A and
      8 type-C) were identified to determine characteristic differences between cases
      with and without combined pathologies. Findings indicated that combined
      pathologies co-occur with FTLD-TDP type-A at a high frequency (50%)-greater than
      when compared to FTLD-TDP type-C cases (12.5%). Those with FTLD-TDP type-A and
      combined pathologies showed significantly longer lifespans (p < 0.05), and longer
      disease durations (p < 0.05), than those with only FTLD-TDP type-A. Cases with
      FTLD-TDP type-A and known genetic mutations tended not to show combined
      pathology. Those with the GRN mutation and FTLD-TDP type-A showed a significantly
      younger age of onset (p < 0.05) and younger age at death (p < 0.01) compared to
      noncarriers. In 1 bvFTD case, we highlight the rare presence of "triple" FTLD-TDP
      type-A, FTLD-tau, and Alzheimer pathology. The ante- and post-mortem features
      associated with combined pathologies in FTLD-related disorders are of useful
      consideration in the stratification of patients to drug trials, and in the
      development of therapeutic targets for FTLD.

PMID- 29584906
TI  - Capillary leak syndrome in Daboia russelii bite-a complication associated with
      poor outcome.
AB  - Background: Capillary leak syndrome (CLS) has been previously observed as a
      complication of Daboia russelii bite but not clearly defined or studied in
      length. This observational case-control study evaluates the mortality along with
      associated clinical and laboratory features. Methods: Twenty-five patients who
      developed CLS were compared with 25 patients without CLS following Daboia
      russelii (Russell's viper) bite. Results: Development of CLS is associated with a
      significantly high risk of mortality; 11 (44%) patients with CLS died compared
      with 1 (4%) control (odds ratio 18.8 [95% confidence interval 2.2 to 161.99],
      p=0.002). Disease-defining manifestations included myalgia (22 [88%]), thirst (20
      [80%]), parotid swelling (15 [60%]), conjunctival chemosis (19 [76%]) and
      hypotension (22 [88%]), which were unobserved in controls. Although several
      clinical and laboratory parameters were found to be predictive for development of
      CLS in univariate analysis, none of them had independent predictive value in
      multivariate analysis. Similarly, development of parotid swelling was the only
      factor with independent predictive value for mortality in multivariate analysis.
      Even though the number of vials of snake antivenom used is more in CLS, it seems
      unlikely to improve the mortality in CLS. Conclusions: This study proves that CLS
      is a well-defined complication of Russell's viper bite with high mortality but
      with clear predictors for the development of CLS and mortality.

PMID- 29584907
TI  - Comment on: IgG4-related disease presenting with raised serum IgG2-real timeline
      of IgG4-RD?

PMID- 29584908
TI  - METHODOLOGY AT CIEMAT WHOLE BODY COUNTER FOR IN VIVO MONITORING OF RADIOIODINE IN
      THE THYROID OF EXPOSED POPULATION IN CASE OF NUCLEAR EMERGENCY.
AB  - Iodine-131 is one of the main concerns from the point of view of radiological
      protection in a short term after a nuclear accident. The WBC Laboratory of CIEMAT
      has developed a methodology for in vivo monitoring of radioiodine in the thyroid
      of exposed individuals in case of emergency. Thyroid-neck phantoms of different
      sizes are required for calibrating the detection systems in appropriate counting
      geometries for the measurement of exposed population. A Low-Energy Germanium
      (LEGe) detector and a Fastscan Counter were calibrated using a set of thyroid
      phantoms fabricated by CIEMAT. Each neck phantom consists of a Lucite cylinder
      with a vial source of 131I. Counting efficiencies depending on age and thyroid
      sizes were obtained to be used to determine the activity of 131I in internally
      contaminated people. DL of 131I varies with the age, being in the range of 5-8 Bq
      for the LEGe detector and 26-42 Bq for the Fastscan. Detection of intakes
      resulting in Committed Effective doses far below 1 mSv are guaranteed for thyroid
      monitoring in a few days after the accidental exposure assuming a scenario of
      acute inhalation or ingestion of 131I by members of the public.

PMID- 29584909
TI  - Spinal stenosis secondary to extramedullary hematopoeisis in beta-thalassaemia.

PMID- 29584910
TI  - Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed
      patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM).
AB  - Background: Sparing of antiretroviral drug classes could reduce the toxicity and
      cost of maintenance treatment for HIV infection. Objectives: To evaluate the non
      inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy
      versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir
      (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA
      viral load <50 copies/mL for the past 12 months and no documented treatment
      failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years.
      The primary endpoint was the proportion of patients without treatment failure at
      week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without
      study treatment discontinuation, a new AIDS-defining illness, or death. Results:
      In the ITT analysis, the primary endpoint was reached by, respectively, 64% and
      71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97),
      yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%).
      Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the
      lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm
      (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r
      monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance
      rarely emerged in the lopinavir/r arm and did not undermine future PI options.
      Two years of lopinavir/r monotherapy had no deleterious clinical impact when
      compared with EFV/FTC/TDF.

PMID- 29584911
TI  - Organ recovery cost assessment in the French healthcare system from 2007 to 2014.
AB  - Background: Organ recovery costs should be assessed to allow efficient and
      sustainable integration of these costs into national healthcare budgets and
      policies. These costs are of considerable interest to health economists,
      hospitals, financial managers and policy makers in most developed countries. This
      study assessed organ recovery costs from 2007 to 2014 in the French healthcare
      system based on the national hospital discharge database and a national cost
      study. The secondary objective was to describe the variability in the population
      of deceased organ donors during this period. Methods: All stays for organ
      recovery in French hospitals between January 2007 and December 2014 were
      quantified from discharge abstracts and valued using a national cost study. Five
      cost evaluations were conducted to explore all aspects of organ recovery
      activities. A sensitivity analysis was conducted to test the methodological
      choice. Trends regarding organ recovery practices were assessed by monitoring
      indicators. Results: The analysis included 12 629 brain death donors, with 28 482
      organs recovered. The mean cost of a hospital stay was ?7469 (SD = ?10, 894). The
      mean costs of separate kidney, liver, pancreas, intestine, heart, lung and heart
      lung block recovery regardless of the organs recovered were ?1432 (SD = ?1342),
      ?502 (SD = ?782), ?354 (SD = ?475), ?362 (SD = ?1559), ?542 (SD = ?955), ?977 (SD
      = ?1196) and ?737 (SD = ?637), respectively. Despite a marginal increase in
      donors, the number of organs recovered increased primarily due to improved
      practices. Conclusion: Although cost management is the main challenge for
      successful organ recovery, other aspects such as organization modalities should
      be considered to improve organ availability.

PMID- 29584912
TI  - Stress preconditioning of rooster semen before cryopreservation improves
      fertility potential of thawed sperm.
AB  - Avian semen cryopreservation is not as successful as that seen in mammals. This
      failure is mostly attributed to unique physiological characteristics of poultry
      semen that make it susceptible to cryo-damages. Utilization of sublethal
      oxidative stress for preconditioning of sperm, as an innovative approach,
      improves the cryo-survival of sperm in certain mammalian species. The purpose of
      this study was to investigate the effects of preconditioning of rooster semen
      with sublethal oxidative stress [very low concentrations of nitric oxide (NO)]
      before cryopreservation on the quality and fertility potential of thawed sperm.
      Semen samples were collected from 20 roosters, twice a wk, and different
      concentrations of NO [0 (NO-0), 0.01 (NO-0.01), 0.1 (NO-0.1), 1 (NO-1), 10 (NO
      10), and 100 MUM (NO-100)] were used to investigate the effects of controlled
      induction of sublethal stress before semen cryopreservation on the thawed sperm
      performance. A significantly higher (P < 0.05) percentage of total motility was
      observed in semen treated with NO-1 compared to NO-0, NO-0.01, NO-0.1, NO-10, and
      NO-100. NO-1 and NO-100 produced the highest and lowest percentages of
      progressive motility, which were significantly different from that of the other
      groups (P < 0.05). A significantly higher (P < 0.05) percentage of sperm
      mitochondria activity was observed in semen exposed to NO-0, NO-0.01, NO-0.1, and
      NO-1. Moreover, the lowest (P < 0.05) concentration of malondialdehyde (MDA) was
      measured in samples treated with NO-1 in comparison to the other groups. Abnormal
      morphology, acrosome integrity, and velocity parameters [velocity average path
      (VAP) and linearity (LIN)] of sperm were not significantly (P > 0.05) affected by
      different concentrations of NO. Sperm exposed to NO-1 produced the highest
      percentage of viable spermatozoa (Annexin-/PI-), which was significantly
      different from the other samples. Finally, rate of fertility after artificial
      insemination was significantly higher (P < 0.05) following treatment with NO-1
      compared to NO-0 and NO-0.1. Application of 1 MUM NO as a sublethal oxidative
      stress before cryopreservation of sperm efficiently increased numerous quality
      indices of thawed sperm as well as its fertility potential.

PMID- 29584913
TI  - Development of Saudi e-health literacy scale for chronic diseases in Saudi
      Arabia: using integrated health literacy dimensions.
AB  - Objective: Health literacy has become a global issue, and it is important that
      patients and individuals are able to use information technology to access health
      information and educational services. The research objective is to develop a
      Saudi e-health literacy scale (SeHL) for measuring e-health literacy among Saudis
      suffering from non-communicable diseases (NCD). Methods: Overall, 14 relevant
      papers in related interdisciplinary fields were reviewed to select the most
      useful literacy dimensions. From these articles, we extracted the most common
      dimensions used to measure e-health literacy across the disciplines. Multiple
      workshops with multidisciplinary team members reviewed and evaluated items for
      SeHL. Results: Four key aspects of e-health literacy-use of technology/media,
      information-seeking, usefulness and confidence-were identified and integrated as
      e-health literacy dimensions. These will be used to measure e-health literacy
      among Saudi patients with NCDs. A translation from Arabic to English was
      performed in order to ensure that translation process was accurate. A SeHL scale
      was developed to measure e-health literacy among Saudi patients. By understanding
      e-health literacy levels, we will be able to create a patient-education system to
      be used by patients in Saudi Arabia. Conclusions: As information technology is
      increasingly used by people of all ages all over the world, e-health literacy has
      been identified as a key factor in determining health outcomes. To date, no
      comprehensive scale exists to assess e-health literacy levels among speakers of
      Arabic, particularly among people with NCD such as diabetes, cardiovascular
      diseases and hypertension.

PMID- 29584915
TI  - Interleukin-1 blockade in cardiovascular diseases: a clinical update.
AB  - Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was
      implicated as a cardiodepressant factor in septic shock, and subsequent pre
      clinical and clinical research has defined important roles for IL-1 in
      atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1
      promotes the formation of the atherosclerotic plaque and facilitates its
      progression and complication. In a large phase III clinical trial of stable
      patients with prior AMI, blocking IL-1 activity using a monoclonal antibody
      prevented recurrent atherothrombotic cardiovascular events. IL-1 also contributes
      to adverse remodelling and left ventricular dysfunction after AMI, and in phase
      II studies, IL-1 blockade quenched the inflammatory response associated with ST
      segment elevation AMI and prevented HF. In patients with established HF, IL-1 is
      thought to impair beta-adrenergic receptor signalling and intracellular calcium
      handling. Phase II studies in patients with HF show improved exercise capacity
      with IL-1 blockade. Thus, IL-1 blockade is poised to enter the clinical arena as
      an additional strategy to reduce the residual cardiovascular risk and/or address
      inflammatory cardiovascular conditions refractory to standard treatments. There
      are several IL-1 blockers available for clinical use, which differ in mechanism
      of action, and potentially also efficacy and safety. While IL-1 blockade is not
      immunosuppressive and not associated with opportunistic infections or an
      increased risk of cancer, fatal infections may occur more frequently while on
      treatment with IL-1 blockers likely due to a blunting of the inflammatory signs
      of infection leading to delayed presentation and diagnosis. We discuss the
      practical use of IL-1 blockade, including considerations for patient selection
      and safety monitoring.

PMID- 29584914
TI  - Antimicrobial resistance of Enterococcus faecium strains isolated from commercial
      probiotic products used in cattle and swine.
AB  - Probiotics, an antibiotic alternative, are widely used as feed additives for
      performance benefits in cattle and swine production systems. Among bacterial
      species contained in probiotics, Enterococcus faecium is common. Antimicrobial
      resistance (AMR), particularly multidrug resistance, is a common trait among
      enterococci because of their propensity to acquire resistance and horizontally
      transfer AMR genes. Also, E. faecium is an opportunistic pathogen, and in the
      United States, it is the second most common nosocomial pathogen. There has been
      no published study on AMR and virulence potential in E. faecium contained in
      probiotic products used in cattle and swine in the United States. Therefore, our
      objectives were to determine phenotypic susceptibilities or resistance to
      antimicrobials, virulence genes (asa1, gelE, cylA, esp, and hyl) and assess
      genetic diversity of E. faecium isolated from commercial products. Twenty-two
      commercially available E. faecium-based probiotic products used in cattle (n =
      13) and swine (n = 9) were procured and E. faecium was isolated and species
      confirmed. Antimicrobial susceptibility testing to determine minimum inhibitory
      concentrations was done by micro-broth dilution method using National
      Antimicrobial Resistance Monitoring Systems Gram-positive Sensititre panel plate
      (CMV3AGPF), and categorization of strains as susceptible or resistant was as per
      Clinical Laboratory and Standards Institute's guidelines. E. faecium strains from
      7 products (3 for swine and 4 for cattle) were pan-susceptible to the 16
      antimicrobials tested. Strains from 15 products (6 for swine and 9 for cattle)
      exhibited resistance to at least one antimicrobial and a high proportion of
      strains was resistant to lincomycin (10/22), followed by tetracycline (4/22),
      daptomycin (4/22), ciprofloxacin (4/22), kanamycin (3/22), and penicillin (2/22).
      Four strains were multidrug resistant, with resistant phenotypes ranging from 3
      to 6 antimicrobials or class. None of the E. faecium strains were positive for
      any of the virulence genes tested. The clonal relationships among the 22 E.
      faecium strains were determined by pulsed-field gel electrophoresis (PFGE)
      typing. A total of 10 PFGE patterns were observed with 22 strains and a few of
      the strains from different probiotic products had identical (100% Dice
      similarity) PFGE patterns. In conclusion, the E. faecium strains in a few
      commercial probiotics exhibited AMR to medically-important antimicrobials, but
      none contained virulence genes.

PMID- 29584916
TI  - A Randomized, Multicenter, Double-Blind, Parallel Pilot Study Assessing the
      Effect of Mechanical Adhesiolysis vs Adhesiolysis with Corticosteroid and
      Hyaluronidase Administration into the Epidural Space During Epiduroscopy.
AB  - Objective: Epiduroscopy is a proven method of diagnosis and treatment for chronic
      radicular pain after spinal surgery, which is known as failed back surgery
      syndrome (FBSS). The aim of the study was to compare the efficacy of drugs (the
      enzyme hyaluronidase and corticosteroid DEPO-Medrol) administrated into the
      epidural space during epiduroscopy, performed within the ventral and ventro
      lateral epidural space with a focus on releasing foraminal adhesions. Methods: 
      Forty-eight patients with diagnosed FBBS were randomized into two groups before
      epiduroscopy. Group A received the standard treatment-mechanical lysis of
      fibrotic tissue in the epidural space. Group B received hyaluronidase and
      corticosteroid methylprednisolone acetate during the procedure. Subjects were
      followed for six and 12 months via scheduled double-blinded examinations by pain
      physicians. Leg and back pain intensity was assessed by an 11-point numerical
      rating scale, and patients' functional disability was assessed by the Oswestry
      Disability Index (ODI). Results: Study subjects showed a significant decrease in
      ODI score in both groups (P < 0.05). Significantly lower pain scores for leg pain
      (P < 0.05) and back pain (P < 0.05) were also recorded after the six-month follow
      up. However, the one-year follow-up showed a return to the baseline ODI values of
      most monitored pain scores in both groups (P > 0.05). Improvement was only noted
      on the NRS for back pain at one-year follow-up (P < 0.05). Conclusions: A
      significant improvement of leg and back pain was found in both groups after six
      months. ODI was significantly improved only in group B in both the six- and 12
      month intervals. Back pain at one-year follow-up was only improved in group B.

PMID- 29584917
TI  - The Effects of Nicotine and Tobacco use on Brain Reward Function: Interaction
      with Nicotine Dependence Severity.
AB  - Introduction: This study investigated the effects of nicotine/tobacco on neural
      activation during performance of a monetary incentivized delay task. Methods:
      Prior to each scan, nonsmokers received nicotine or placebo nasal spray and
      smokers were smoking satiated or 24-hours withdrawn. During the scan,
      participants made timed responses to reward-related cues and received feedback.
      Parameter estimates from cue- and feedback-related activation in medial
      prefrontal regions and the nucleus accumbens (NAcc) were extracted and underwent
      within- and between-group analyses. Smokers' nicotine dependence severity was
      included as a continuous predictor variable for neural activation. Results: Among
      smokers (n = 21), withdrawal decreased cue-related activation in the
      supplementary motor area and ventromedial prefrontal cortex, and the difference
      in activation (satiety > withdrawal) in these regions negatively correlated with
      nicotine dependence severity (Fagerstrom Test for Nicotine Dependence). Among
      nonsmokers (n = 22), nicotine increased the difference in NAcc activation between
      rewarded and non-rewarded feedback phases. Tobacco withdrawal and acute nicotine
      also had widespread effects on activation throughout the brain during the
      feedback phase. Conclusions: Acute nicotine in nonsmokers may have increased the
      salience of feedback information, but produced few effects on reward-related
      activation overall, perhaps reflecting nicotine's modest, indirect effects on
      reward processing. Conversely, tobacco withdrawal decreased activation compared
      to satiety, and this difference between conditions correlated with nicotine
      dependence severity. This suggests that as smokers become more dependent on
      nicotine, tobacco withdrawal has a more pronounced effect on reward processing.
      Implications: Relative to the acute effects of nicotine in nonsmokers, withdrawal
      from daily tobacco use had more significant effects on reward-related brain
      activation. This study suggests that the effects of tobacco withdrawal on reward
      related brain function interact with subjects' level of nicotine dependence
      severity. These are potentially important sources of variability that could
      contribute to smoking cessation outcomes.

PMID- 29584918
TI  - Human Immunization With a Polymorphic Malaria Vaccine Candidate Induced
      Antibodies to Conserved Epitopes That Promote Functional Antibodies to Multiple
      Parasite Strains.
AB  - Background: Overcoming antigenic diversity is a key challenge in the development
      of effective Plasmodium falciparum malaria vaccines. Strategies that promote the
      generation of antibodies targeting conserved epitopes of vaccine antigens may
      provide protection against diverse parasites strains. Understanding differences
      between vaccine-induced and naturally acquired immunity is important to achieving
      this goal. Methods: We analyzed antibodies generated in a phase 1 human vaccine
      trial, MSP2-C1, which included 2 allelic forms of MSP2, an abundant vaccine
      antigen on the merozoite surface. Vaccine-induced responses were assessed for
      functional activity against multiple parasite strains, and cross-reactivity of
      antibodies was determined using competition ELISA and epitope mapping approaches.
      Results: Vaccination induced cytophilic antibody responses with strain
      transcending opsonic phagocytosis and complement-fixing function. In contrast to
      antibodies acquired via natural infection, vaccine-induced antibodies were
      directed towards conserved epitopes at the C-terminus of MSP2, whereas naturally
      acquired antibodies mainly targeted polymorphic epitopes. Functional activity of
      C-terminal-targeted antibodies was confirmed using monoclonal antibodies that
      promoted opsonic phagocytosis against multiple parasite strains. Conclusion:
      Vaccination generated markedly different responses to polymorphic antigens than
      naturally acquired immunity and targeted conserved functional epitopes. Induction
      of antibodies targeting conserved regions of malaria antigens provides a
      promising vaccine strategy to overcome antigenic diversity for developing
      effective malaria vaccines.

PMID- 29584919
TI  - Genetic diversity of Orientia tsutsugamushi strains circulating in Northeast
      India.
AB  - Background: Scrub typhus, caused by the intracellular bacteria Orientia
      tsutsugamushi is widely distributed in Southeast Asian countries with
      antigenically divergent strains reported across the Asia-Pacific belt. The
      present study was conducted to characterize the circulating strains of Orientia
      tsutsugamushi prevailing in two Northeastern states of India-the gateway to most
      Southeast Asian countries. Methods: A total of 278 (98 clinical and 180 field
      collected) scrub typhus positive blood samples collected from December 2014 to
      December 2016 were subjected for amplification of partial 56 KDa, 47 KDa and
      16SrRNA genes of Orientia. Results: Highest number of PCR positives were obtained
      for 56 KDa gene (17.3%); followed by 11.2% for 47 KDa gene and 5.1% for 16S rRNA
      gene. High degree of genetic diversity was identified among the identified
      strains, especially within the 56 KDa gene. Different strains of Orientia
      circulate in the northeastern part of India, with a pre-dominance of Karp-like
      strains. Independently branched isolates formed distinct clades, suggesting the
      possibility of a new strain type of Orientia. Conclusion: This study provides
      insight into the genetic and evolutionary relationship of Orientia strains
      prevalent in this part of the country. Understanding the regional genetic
      diversity is crucial for its implications in vaccine developments strategies as
      well as sero-diagnostics. Accession numbers: KU163366, KY594249, KY594248,
      KY594251, KU163359, KU163361, KU163363, KU163369, KY594250, KP067915, KU163373,
      KU163372, KU163370, KU163364, KU163362, KY594247, KY594252, KU163360, KU163365,
      KU163367, KU163368, KU163371, KX1555826, KY594257, KY594255, KY594256, KX155825,
      KX155829, KX155827, KX155828, KY594254, KY594253, KY594258, KY583503, KY583499,
      KY583501, KY583500, KY583502.

PMID- 29584920
TI  - Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous
      Ovarian Cancer.
AB  - Background: To identify clinically relevant genomic rearrangement signatures in
      high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis
      of sequenced HGSOC whole-tumor genomes. Methods: Clinical data and whole-genome
      sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the
      Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were
      identified, and non-negative matrix factorization (NMF) was used to extract
      rearrangement signatures. The cohort was then dichotomized around the median
      signature contribution, and overall survival (OS) was analyzed. An independent
      cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was
      also examined. The TCGA cohort was dichotomized around the median similarity
      between tumor copy number profile and a prognostic rearrangement signature, and
      OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox
      regression methods. All statistical tests were two-sided. Results: We identified
      five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10
      kilobase to 10 megabase deletions and tandem duplications, and patients whose
      tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was
      22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3
      high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group
      (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent
      TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in
      the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in
      the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001).
      Conclusion: A novel genomic rearrangement signature is associated with poor
      prognosis in HGSOC.

PMID- 29584921
TI  - Toward methylation-based classification of central nervous system tumors.

PMID- 29584922
TI  - Crossing Phenotype Heritability and Candidate Gene Expression in Grafted Black
      Lipped Pearl Oyster Pinctada margaritifera, an Animal Chimera.
AB  - Grafting mantle tissue of a donor pearl oyster into the gonad of a recipient
      oyster results in the formation of a chimera, the pearl sac. The phenotypic
      variations of this chimera are hypothesized to be the result of interactions
      between the donor and recipient genomes. In this study, the heritability of
      phenotypic variation and its association with gene expression were investigated
      for the first time during Pinctada margaritifera pearl production. Genetic
      variance was evaluated at different levels, 1) before the graft operation
      (expression in graft tissue), 2) after grafting (pearl sac tissue expression in
      chimera), and 3) on the product of the graft (pearl phenotype traits) based on
      controlled biparental crosses and the F1 generation. Donor-related genetic
      parameter estimates clearly demonstrate heritability for nacre weight and
      thickness, darkness and color, and surface defects and grade, which signifies a
      genetic basis in the donor oyster. In graft relative gene expression, the value
      of heritability was superior to 0.20 in for almost all genes; whereas in pearl
      sac, heritability estimates were low (h2 < 0.10; except for CALC1 and Aspein).
      Pearl sac expression seems to be more influenced by residual variance than the
      graft, which can be explained by environmental effects that influence pearls sac
      gene expression and act as a recipient additive genetic component. The
      interactions between donor and recipient are very complex, and further research
      is required to understand the role of the recipient oysters on pearl phenotypic
      and gene expression variances.

PMID- 29584923
TI  - Rescue Therapy for Procedural Complications Associated With Deployment of Flow
      Diverting Devices in Cerebral Aneurysms.
AB  - Flow diverting devices (FDDs) have revolutionized the treatment of
      morphologically complex intracranial aneurysms such as wide-necked, giant, or
      fusiform aneurysms. Although FDDs are extremely effective, they carry a small yet
      significant risk of intraprocedural complications. As the implementation of these
      devices increases, the ability to predict and rapidly treat complications,
      especially those that are iatrogenic or intraprocedural in nature, is becoming
      increasingly more necessary.Our objective in this paper is to provide a
      descriptive summary of the various types of intraprocedural complications that
      may occur during FDDs deployment and how they may best be treated. A systematic
      and qualitative review of the literature was conducted using electronic databases
      MEDLINE and Google Scholar. Searches consisted of Boolean operators "AND" and
      "OR" for the following terms in different combinations: "aneurysm,"
      "endovascular," "flow diverter," "intracranial," and "pipeline."A total of 94
      papers were included in our analysis; approximately 87 of these papers dealt with
      periprocedural endovascular (mainly related to FDDs) complications and their
      treatment; 7 studies concerned background material. The main categories of
      periprocedural complications encountered during deployment of FDDs are failure of
      occlusion, parent vessel injury and/or rupture, spontaneous intraparenchymal
      hemorrhage, migration or malposition of the FDDs, thromboembolic or ischemic
      events, and side branch occlusionPeriprocedural complications occur mainly due to
      thromboembolic events or mechanical issues related to device deployment and
      placement. With increasing use and expanding versatility of FDDs, the
      understanding of these complications is vital in order to effectively manage such
      situations in a timely manner.

PMID- 29584924
TI  - An Open-label Randomized Controlled Trial to Compare Weight Gain of Very Low
      Birth Weight Babies with or without Addition of Coconut Oil to Breast Milk.
AB  - Background: Nutritional guidelines involving the feeding of very low birth weight
      babies (VLBW) recommend addition of Human Milk Fortifiers to breast milk. Owing
      to financial constraints, it is a practice in low- and middle-income countries
      (LMIC) to add coconut oil to aid better weight gain. There are inadequate data on
      improvement of growth parameters with oral coconut oil supplementation of breast
      milk. Methods: In this randomized controlled trial, we measured growth parameters
      and body composition of 60 babies who received either breast milk with coconut
      oil or breast milk alone. Randomization was stratified according to intrauterine
      growth appropriate for gestational age (n = 30) and small for gestational age (n
      = 30). Results: There was no difference in weight gain between the two groups.
      The weight gain velocity was 15 +/- 3.6 and 14.4 +/- 3.4 g/kg/day (p value =
      0.49) in the breast milk alone and in the breast milk with coconut oil group,
      respectively. There was no difference in increase in head circumference and
      length. Triceps skinfold thickness (n = 56) was similar in both groups, but
      subscapular skinfold thickness was significantly more in the coconut oil group.
      Total body fat percentage did not differ between the groups (25.2 +/- 4.3 vs.
      25.5 +/- 4.3%, p = 0.79). Conclusion: Oral supplementation of coconut oil along
      with breast milk did not increase growth parameters or result in change in body
      composition in very low birth weight (VLBW) babies.

PMID- 29584925
TI  - EVALUATING EXTREMELY LOW FREQUENCY MAGNETIC FIELDS IN THE REAR SEATS OF THE
      ELECTRIC VEHICLES.
AB  - In the electric vehicles (EVs), children can sit on a safety seat installed in
      the rear seats. Owing to their smaller physical dimensions, their heads,
      generally, are closer to the underfloor electrical systems where the magnetic
      field (MF) exposure is the greatest. In this study, the magnetic flux density (B)
      was measured in the rear seats of 10 different EVs, for different driving
      sessions. We used the measurement results from different heights corresponding to
      the locations of the heads of an adult and an infant to calculate the induced
      electric field (E-field) strength using anatomical human models. The results
      revealed that measured B fields in the rear seats were far below the reference
      levels by the International Commission on Non-Ionizing Radiation Protection.
      Although small children may be exposed to higher MF strength, induced E-field
      strengths were much lower than that of adults due to their particular physical
      dimensions.

PMID- 29584926
TI  - Evaluation of Complementary and Integrative Health Approaches Among US Veterans
      with Musculoskeletal Pain Using Propensity Score Methods.
AB  - Objectives: To examine the treatment effectiveness of complementary and
      integrative health approaches (CIH) on chronic pain using Propensity Score (PS)
      methods. Design, Settings, and Participants: A retrospective cohort of 309,277
      veterans with chronic musculoskeletal pain assessed over three years after
      initial diagnosis. Methods: CIH exposure was defined as one or more clinical
      visits for massage, acupuncture, or chiropractic care. The treatment effect of
      CIH on self-rated pain intensity was examined using a longitudinal model. PS
      matching and inverse probability of treatment weighting (IPTW) were used to
      account for potential selection and confounding biases. Results: At baseline,
      veterans with (7,621) and without (301,656) CIH exposure differed significantly
      in 21 out of 35 covariates. During the follow-up period, on average CIH
      recipients had 0.83 (95% confidence interval [CI] = 0.77 to 0.89) points higher
      pain intensity ratings (range = 0-10) than nonrecipients. This apparent
      unfavorable effect size was reduced to 0.37 (95% CI = 0.28 to 0.45) after PS
      matching, 0.36 (95% CI = 0.29 to 0.44) with IPTW on the treated (IPTW-T)
      weighting, and diminished to null when integrating IPTW-T with PS matching
      (0.004, 95% CI = -0.09 to 0.10). An alternative IPTW model and conventional
      covariate adjustment appeared least powerful in terms of potential bias
      reduction. Sensitivity analyses restricting the follow-up period to one year
      after CIH initiation derived consistent results. Conclusions: PS-based causal
      methods successfully eliminated baseline difference between exposure groups in
      all measured covariates, yet they did not detect a significant difference in the
      self-rated pain intensity outcome between veterans who received CIHs and those
      who did not during the follow-up period.

PMID- 29584927
TI  - Impact of replacing radiographic sacroiliitis by magnetic resonance imaging
      structural lesions on the classification of patients with axial
      spondyloarthritis.
AB  - Objectives: To investigate in patients with chronic back pain of a short
      duration, the utility of adding structural MRI lesions of the SI joints to the
      imaging criterion of the Assessment of SpondyloArthritis International Society
      (ASAS) axial SpA (axSpA) criteria and the utility of replacement of radiographic
      sacroiliitis by structural MRI lesions. Methods: MRI STIR (inflammation, MRI-SI),
      MRI T1-weighted images (structural lesions, MRI-SI-s) and radiographs of the SI
      joints of patients in the SPondyloArthritis Caught Early-cohort (chronic back
      pain: ?3 months, ?2 years; onset <45 years) were scored by two well-calibrated
      readers. Previously proposed cut-offs for a positive MRI-SI-s were used (based on
      <5% prevalence in no-SpA patients): erosions ?3, fatty lesions ?3, fatty lesions
      and/or erosions (erosions/fatty lesions) ?5. Using the definitions of MRI-SI-s,
      patients were classified according to the ASAS axSpA criteria. Results: Twenty
      nine of 294 patients were modified New York (mNY) positive and 32 were MRI-SI-s
      positive (erosions/fatty lesions ?5). Agreement between mNY and MRI-SI-s
      (erosions/fatty lesions ?5) was moderate (kappa: 0.58). Using the erosions/fatty
      lesions ?5 cut-off, 3/294 additional patients were classified as axSpA (adding
      MRI). Using this cut-off instead of mNY (replacing mNY), classification did not
      change in 286 patients (97.3%), but 5 patients (1.7%) would not be classified as
      axSpA and 3 previously unclassified patients (1.0%) would be classified as axSpA.
      Similar results were seen for the other cut-offs (erosions ?3 and fatty lesions
      ?3). Conclusion: Assessment of structural lesions (fatty lesions and erosions) on
      MRI-SI instead of or in addition to conventional radiographs does not lead to a
      different ASAS axSpA classification in most of the patients with early disease
      onset. This suggests that structural lesions (fatty lesions and erosions) can be
      reliably used in the ASAS axSpA classification of patients, as both addition and
      replacement of radiographs of the SI joints.

PMID- 29584928
TI  - Thoracic enhanced recovery with ambulation after surgery: a 6-year experience.
AB  - OBJECTIVES: Our institution implemented a protocol known as thoracic enhanced
      recovery with ambulation after surgery (T-ERAS) in thoracic operations. The
      objective was early ambulation starting in the postoperative ambulatory care
      unit. METHODS: Video-assisted thoracoscopic surgery lobectomy patients are placed
      on a chair in the preoperative area and then walked to the operating room.
      Postoperatively, patients are placed on a chair as soon as possible. Our target
      ambulation goal was 250 feet within 1 h of extubation. Patients then walk to
      their hospital room. T-ERAS adoption and outcomes were compared to a pre-T-ERAS
      period, in addition to the comparing early and late T-ERAS cohorts. RESULTS: Over
      6 years, 304 patients on T-ERAS underwent a planned video-assisted thoracoscopic
      surgery lobectomy. Median age was 67 years (range 41-87 years). The target goal
      was achieved in 187 of 304 (61.5%) patients and 277 of 304 (91.1%) patients
      ambulated 250 feet at any time in the postoperative ambulatory care unit. The T
      ERAS period had a median length of stay of 1 day vs 2 days in the pre-T-ERAS
      period (P < 0.001). There were low rates of pneumonia (2/304, 0.7%), atrial
      fibrillation (12/304, 4.0%) and no postoperative mortalities for T-ERAS. The
      target goal was achieved at a greater rate in the late (92/132, 72.0%) versus
      early (28/75, 37%) T-ERAS cohort. The mean time to ambulation was reduced in the
      late cohort (46-81 min). CONCLUSIONS: Early postoperative ambulation was feasible
      and considered key in achieving low morbidity after video-assisted thoracoscopic
      surgery lobectomy. Adoption of T-ERAS improved over time. Further studies will
      help define adoptability at other sites and validate impact on improving
      outcomes.

PMID- 29584929
TI  - Correlative electron energy loss spectroscopy and cathodoluminescence
      spectroscopy on three-dimensional plasmonic split ring resonators.
AB  - We present the surface plasmon resonance modes in three-dimensional (3D) upright
      split ring resonators (SRR) as studied by correlative cathodoluminescence (CL)
      spectroscopy in a scanning electron microscope (SEM) and electron energy loss
      spectroscopy (EELS) in a transmission electron microscope. We discuss the
      challenges inherent in studying the plasmon modes of a 3D nanostructure and how
      meeting these challenges benefits from the complementary use of EELS and SEM-CL.
      With the use of EELS, we detect a strong first order mode in the SRR; with
      comparison to simulations, we are able to identify this as the well-known
      magnetic dipole moment of the SRR. Combining the EELS spectra with SEM-CL on the
      same structure reveals the higher order modes present in this 3D nanostructure,
      which we link to the coupling and hybridization of rim modes present in the two
      upright hollow pillars of the split ring.

PMID- 29584930
TI  - EDGE 2017 - Enhanced Data Generated by Electrons, Okinawa, May 2017.

PMID- 29584931
TI  - Evaluation of feed efficiency traits for genetic improvement in Japanese Black
      cattle.
AB  - We evaluated the genetic relationships (1) among feed efficiency traits with
      different fattening periods, (2) between feed efficiency traits and growth
      traits, and (3) between feed efficiency traits and carcass traits, to determine
      the influence of genetic factors on feed efficiency traits. In total, 4,578
      Japanese Black cattle from a progeny testing program were used. Residual feed
      intake (RFI), residual BW gain (RG), and residual intake and BW gain (RIG) were
      defined as feed efficiency traits, and were measured for the first half
      (approximately 9 to 15 months of age), latter half (approximately 15 to 21 months
      of age), and total period of fattening (approximately 9 to 21 months of age). A
      single-trait animal model for estimating heritability and a two-trait animal
      model for estimating genetic and phenotypic correlations were used. The
      heritability estimates for RFI, RG, and RIG were different in each fattening
      period, ranging from 0.36 to 0.46, 0.19 to 0.28, and 0.28 to 0.34, respectively,
      and the heritability estimates for the total fattening period were greater than
      those for the first and latter halves separately. RIG showed the greatest
      preferred genetic correlation, with a greater feed conversion ratio than the
      other feed efficiency traits (ranging from -0.84 to -0.96). RG in the first and
      latter halves of the fattening period had different genetic correlations with the
      growth starting point (0.82 and -0.06, respectively) and maturity rate (0.49 and 
      0.51, respectively) of the Gompertz growth curve parameters, and is strongly
      dependent on the different fattening periods. Feed efficiency traits in different
      fattening periods had low genetic correlations with the carcass traits (from 
      0.05 to 0.19 for RFI; from 0.02 to 0.31 for RG; and from -0.11 to 0.20 for RIG).
      This study indicated the possibility for genetic improvement through the
      selection of high-RIG animals to decrease feed intake and increase BW gain
      without any unfavorable correlated responses affecting mature (asymptotic) weight
      and carcass grade.

PMID- 29584933
TI  - President's Message: A Year of Advocacy for Our Patients and Our Field of Pain
      Medicine.

PMID- 29584932
TI  - Structure-Dependent Modulation of Aryl Hydrocarbon Receptor-Mediated Activities
      by Flavonoids.
AB  - Dietary flavonoids are used in treatment of multiple diseases, and their
      antiinflammatory effects in the intestine are due, in part, to interactions with
      gut microflora and possibly due to modulation of aryl hydrocarbon receptor (AhR)
      signaling. In this study, we investigated the structure-dependent AhR activity of
      14 flavonoids in Caco2 colon cancer cells using induction of CYP1A1 and UGT1A1
      gene expression as endpoints. A major structural determinant for AhR activation
      was the number of hydroxyl groups where pentahydroxyflavonoids (with the
      exception of morin) > hexahydroxyflavonoids > tetra-/trihydroxyflavonoids, and
      some of the latter compounds such as apigenin exhibited AhR antagonist activity
      for induction of CYP1A1. Simulations suggest that while quercetin and apigenin
      interact primarily with the same residues, the strength of interactions between
      specific AhR residues with CYP1A1 agonist, quercetin, in comparison with CYP1A1
      antagonist, apigenin, is different; thus, such interactions are presumably
      indicative of potential switches for modulating CYP1A1 activity. The structure
      dependent effects of the hydroxyl flavonoids on induction of UGT1A1 were similar
      to that observed for induction of CYP1A1 except that luteolin and apigenin
      induced UGT1A1 levels similar to that observed for TCDD, whereas both compounds
      were AhR antagonists for CYP1A1. Thus, the effects of the flavonoids in Caco2
      cells on Ah-responsiveness and interactions with butyrate were both ligand
      structure- and response-dependent and these activities are consistent with
      hydroxyflavonoids being selective AhR modulators.

PMID- 29584934
TI  - Estimation of carcass composition using rib dissection of calf-fed Holstein
      steers supplemented zilpaterol hydrochloride.
AB  - A serial harvest was conducted every 28 d from 254 to 534 d on feed (DOF) to
      quantify changes in growth and composition of calf-fed Holstein steers (n = 115,
      initial body weight (BW) = 449.2 +/- 19.9 kg). One-half were supplemented with
      the beta-2 adrenergic agonist zilpaterol hydrochloride (ZH; 8.33 mg/kg 100% dry
      matter (DM) basis) during the final 20 d followed by a 3-d withdrawal prior to
      harvest; the remainder was fed a non-ZH control (CON) ration. Five steers were
      randomly selected and harvested after 226 DOF which served as a reference point
      for modeling purposes. Fabricated carcass soft tissue was ground, mixed, and
      subsampled for proximate analysis. Moreover, following the traditional method of
      rib dissection which includes the 9th, 10th, and 11th rib contained within the
      IMPS 103 primal, the relationship of carcass chemical composition to 9-10-11 rib
      composition was evaluated. Carcasses in this investigation had more (P < 0.01)
      separable lean, fat, ash, and moisture concomitant with less bone and ether
      extract than rib dissections. However, protein levels were similar (P = 0.27)
      between carcasses and rib dissections. Using regression procedures, models were
      constructed to describe the relationship of rib dissection (RD) composition
      including separable lean (RDSL), separable fat (RDSF), separable bone (RDSB),
      ether extract (RDEE), protein (RDP), moisture (RDM), and ash (RDA) with carcass
      composition. Carcass lean (CL), carcass fat (CF), and carcass bone (CB) were
      correlated (P < 0.01) with RDSL, RDSF, and RDSB with simple r values of 0.41,
      0.71, and 0.50, respectively. Chemical composition of the rib and carcass,
      carcass ether extract (CEE), carcass protein (CP), carcass moisture (CM), and
      carcass ash (CA) were correlated (P <= 0.01) with simple r values of 0.75, 0.31,
      0.66, and 0.37, respectively. Equations to predict carcass fatness from rib
      dissection variables and ZH supplementation status were only able to account for
      50 and 56%, of the variability of CF and CEE, respectively. Overall, the
      relationships quantified and equations developed in this investigation do not
      support use of 9/10/11 rib dissection for estimation of carcass composition of
      calf-fed Holstein steers.

PMID- 29584935
TI  - Beyond Defense: Multiple Functions of Benzoxazinoids in Maize Metabolism.
AB  - Benzoxazinoids are a class of indole-derived plant metabolites that function in
      defense against numerous pests and pathogens. Due to their abundance in maize
      (Zea mays) and other important cereal crops, benzoxazinoids have been the subject
      of extensive research for >50 years. Whereas benzoxazinoids can account for 1% or
      more of the dry weight in young seedlings constitutively, their accumulation in
      older plants is induced locally by pest and pathogen attack. Although the
      biosynthetic pathways for most maize benzoxazinoids have been identified,
      unanswered questions remain about the developmental and defense-induced
      regulation of benzoxazinoid metabolism. Recent research shows that, in addition
      to their central role in the maize chemical defense repertoire, benzoxazinoids
      may have important functions in regulating other defense responses, flowering
      time, auxin metabolism, iron uptake and perhaps aluminum tolerance. Investigation
      of natural variation in maize benzoxazinoid accumulation, which is greatly
      facilitated by recent genomics advances, will have a major impact in this
      research area by leading to the discovery of previously unknown genes and
      functions of benzoxazinoid metabolism.

PMID- 29584936
TI  - Shock Tube/Laser Absorption and Kinetic Modeling Study of Triethyl Phosphate
      Combustion.
AB  - Pyrolysis and oxidation of triethyl phosphate (TEP) were performed in the
      reflected shock region at temperatures of 1462-1673 K and 1213-1508 K,
      respectively, and at pressures near 1.3 atm. CO concentration time histories
      during the experiments were measured using laser absorption spectroscopy at
      4580.4 nm. Experimental CO yields were compared with model predictions using the
      detailed organophosphorus compounds (OPC) incineration mechanism from the
      Lawrence Livermore National Lab (LLNL). The mechanism significantly underpredicts
      CO yield in TEP pyrolysis. During TEP oxidation, predicted rate of CO formation
      was significantly slower than the experimental results. Therefore, a new improved
      kinetic model for TEP combustion was developed, which was built upon the
      AramcoMech2.0 mechanism for C0-C2 chemistry and the existing LLNL submechanism
      for phosphorus chemistry. Thermochemical data of 40 phosphorus (P)-containing
      species were reevaluated, either using recently published group values for P
      containing species or by quantum chemical calculations (CBS-QB3). The new
      improved model is in better agreement with the experimental CO time histories
      within the temperature and pressure conditions tested in this study. Sensitivity
      analysis was used to identify important reactions affecting CO formation, and
      future experimental/theoretical studies on kinetic parameters of these reactions
      were suggested to further improve the model. To the best of our knowledge, this
      is the first study of TEP kinetics in a shock tube under these conditions and the
      first time-resolved laser-based species time history data during its pyrolysis
      and oxidation.

PMID- 29584938
TI  - Long-Range Self-Assembly via the Mutual Lorentz Force of Plasmon Radiation.
AB  - Long-range interactions often proceed as a sequence of hopping through
      intermediate, statistically favored events. Here, we demonstrate predictable
      mechanical dynamics of particles that arise from the Lorentz force between
      plasmons. Even if the radiation is weak, the nonconservative Lorentz force
      produces stable locations perpendicular to the plasmon oscillation; over time,
      distinct patterns emerge. Experimentally, linearly polarized light illumination
      leads to the formation of 80 nm diameter Au nanoparticle chains, perpendicularly
      aligned, with lengths that are orders of magnitude greater than their plasmon
      near-field interaction. There is a critical intensity threshold and optimal
      concentration for observing self-assembly.

PMID- 29584937
TI  - Collective Effects in Second-Harmonic Generation from Plasmonic Oligomers.
AB  - We investigate collective effects in plasmonic oligomers of different symmetries
      using second-harmonic generation (SHG) microscopy with cylindrical vector beams
      (CVBs). The oligomers consist of gold nanorods that have a longitudinal plasmon
      resonance close to the fundamental wavelength that is used for SHG excitation and
      whose long axes are arranged locally such that they follow the distribution of
      the transverse component of the electric field of radially or azimuthally
      polarized CVBs in the focal plane. We observe that SHG from such rotationally
      symmetric oligomers is strongly modified by the interplay between the
      polarization properties of the CVB and interparticle coupling. We find that the
      oligomers with radially oriented nanorods exhibit small coupling effects. In
      contrast, we find that the oligomers with azimuthally oriented nanorods exhibit
      large coupling effects that lead to silencing of SHG from the whole structure.
      Our experimental results are in very good agreement with numerical calculations
      based on the boundary element method. The work describes a new route for studying
      coupling effects in complex arrangements of nano-objects and thereby for
      tailoring the efficiency of nonlinear optical effects in such structures.

PMID- 29584939
TI  - Aglycone Ebselen and beta-d-Xyloside Primed Glycosaminoglycans Co-contribute to
      Ebselen beta-d-Xyloside-Induced Cytotoxicity.
AB  - Most beta-d-xylosides with hydrophobic aglycones are nontoxic primers for
      glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated
      to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen beta-d
      xyloside (8A) showed significant cytotoxicity in human cancer cells. The
      following facts indicated that the aglycone Ebselen and beta-d-xyloside primed
      glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen
      induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2.
      8A augmented early and late phase cancer cell apoptosis significantly compared to
      that of Ebselen and 8B-D; 3. Both 8A and phenyl-beta-d-xyloside primed
      glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells;
      4. Glycosaminoglycans could be detected inside of cells only when treated with
      8A, indicating Ebselen contributed to the unique property of intracellular
      localization of the primed glycosaminoglycans. Thus, 8A represents a lead
      compound for the development of novel antitumor strategy by targeting
      glycosaminoglycans.

PMID- 29584940
TI  - Spontaneous Symmetry Breaking Facilitates Metal-to-Ligand Charge Transfer: A
      Quantitative Two-Photon Absorption Study of Ferrocene-phenyleneethynylene
      Oligomers.
AB  - Change of the permanent molecular electric dipole moment, DeltaMU, in a series of
      nominally centrosymmetric and noncentrosymmteric ferrocene-phenyleneethynylene
      oligomers was estimated by measuring the two-photon absorption cross-section
      spectra of the lower energy metal-to-ligand charge-transfer transitions using
      femtosecond nonlinear transmission method and was found to vary in the range up
      to 12 D, with the highest value corresponding to the most nonsymmetric system.
      Calculations of the DeltaMU performed by the TD-DFT method show quantitative
      agreement with the experimental values and reveal that facile rotation of the
      ferrocene moieties relative to the organic ligand breaks the ground-state
      inversion symmetry in the nominally symmetric structures.

PMID- 29584941
TI  - Vibronic Coherence in the Charge Separation Process of the Rhodobacter
      sphaeroides Reaction Center.
AB  - Two-dimensional electronic spectroscopy was applied to a variant of the reaction
      center (RC) of purple bacterium Rhodobacter sphaeroides lacking the primary
      acceptor ubiquinone in order to understand the ultrafast separation and transfer
      of charge between the bacteriochlorin cofactors. For the first time,
      characteristic 2D spectra were obtained for the participating excited and charge
      transfer states, and the electron-transfer cascade (including two different
      channels, the P* and B* channels) was fully mapped. By analyzing quantum beats
      using 2D frequency maps, excited-state vibrational modes at 153 and 33 cm-1 were
      identified. We speculate that these modes couple to the charge separation (CS)
      process and collectively optimize the CS and are responsible for the superhigh
      efficiency.

PMID- 29584942
TI  - Predominated Thermodynamically Controlled Reactions for Suppressing Cross
      Nucleations in Formation of Multinary Substituted Tetrahedrite Nanocrystals.
AB  - Group I-II-V-VI semiconducting Cu12- xM xSb4S13 (M = ZnII, CdII, MnII and CuII)
      substituted tetrahedrite nanostructures remain a new class of multinary materials
      that have not been widely explored yet. Having different ions, the formation
      process of these nanostructures always has the possibility of formation of cross
      nucleations. Minimizing the reaction time, herein, a predominantly thermodynamic
      control approach is reported, which decouples the quaternary nucleations from
      their possible cross nucleations. As a consequence, possible cross nucleations
      were prevented and a series of nearly monodisperse intriguing substituted
      tetrahedrite nanostructures were formed. The possible LaMer plot for the single-
      and multimaterial nucleations is also proposed. Further, bandgaps of all of these
      new materials are calculated, and preliminarily, the applicability of these
      materials is tested for photoelectrochemical water splitting.

PMID- 29584943
TI  - Cobalt(II)/ N-Hydroxyphthalimide-Catalyzed Cross-Dehydrogenative Coupling
      Reaction at Room Temperature under Aerobic Condition.
AB  - This work reports a cobalt(II)/ N-hydroxyphthalimide (NHPI)-catalyzed cross
      dehydrogenative oxidative coupling of N-aryl tetrahydroisoquinolines with various
      pro-nucleophiles, such as indoles, nitroalkanes, and trialkylphosphites, active
      methylene compounds, and other nucleophiles, such as cyanide (ethyl
      cyanoformate), at room temperature under aerobic conditions. The present protocol
      is operationally simple and can be carried out without photoirradiation and under
      peroxide-free conditions, even on a gram scale, to afford the products in good to
      excellent yields. On the basis of mass spectrometry and control experiments, a
      catalytic reaction pathway has been proposed.

PMID- 29584944
TI  - Paddle-Wheel BODIPY-Hexaoxatriphenylene Conjugates: Participation of Redox-Active
      Hexaoxatriphenylene in Excited-State Charge Separation to Yield High-Energy
      Charge-Separated States.
AB  - Hexaoxatriphenylene, a scaffold linker often utilized in building covalent
      organic frameworks, is shown to be electroactive and a useful entity to build
      light energy-harvesting donor-acceptor systems. To demonstrate this, new donor
      acceptor conjugates have been synthesized by employing BODIPY as a sensitizer.
      Excited-state electron transfer leading to high-energy charge-separated states,
      useful to drive energy-demanding photocatalytic reactions, from the electron-rich
      hexaoxatriphenylene to 1BODIPY*, in the synthesized tri-BODIPY
      hexaoxatriphenylene "paddle-wheel" conjugates, has been successfully demonstrated
      using femtosecond transient absorption spectroscopy. The measured rate of charge
      separation was in the range of ~3-10 * 1011 s-1, revealing ultrafast charge
      separation.

PMID- 29584945
TI  - Diffusivity of Carbon Dioxide in Aqueous Solutions under Geologic Carbon
      Sequestration Conditions.
AB  - Accurate assessment of the long-term security of geologic carbon sequestration
      requires knowledge of the mobility of carbon dioxide in brines under pressure and
      temperature conditions that prevail in subsurface aquifers. Here, we report Raman
      spectroscopic measurements of the rate of CO2 diffusion in water and brines as a
      function of pressure, salinity, and concentration of CO2. In pure water at 50 +/-
      2  degrees C and 90 +/- 2 bar, we find the diffusion coefficient, D, to be (3.08
      +/- 0.03) * 10-9 m2/s, a value that is consistent with a recent microfluidic
      study but lower than earlier PVT measurements. Under reservoir conditions,
      salinity affects the mobility of CO2 significantly and D decreased by 45% for a 4
      M solution of NaCl. We find significant differences of diffusivity of CO2 in
      brines (0-4 M NaCl), in both the absolute values and the trend compared to the
      Stokes-Einstein prediction under our experimental conditions. We observe that D
      decreases significantly at the high CO2 concentrations expected in subsurface
      aquifers (~15% reduction at 0.55 mol/kg of CO2) and provides an empirical
      correction to the commonly reported D values that assume a tracer concentration
      dependence on diffusivity.

PMID- 29584946
TI  - A Second Glass Transition in Pressure Collapsed Type II Clathrate Hydrates.
AB  - Type II clathrate hydrates (CHs) M.17 H2O, with M = tetrahydrofuran (THF) or 1,3
      dioxolane, are known to collapse, or amorphize, on pressurization to ~1.3 GPa in
      the temperature range 77-140 K. On heating at 1 GPa, these pressure-amorphized CH
      states show a weak, stretched sigmoid-shaped, heat-capacity increase because of a
      glass transition. Here we use thermal conductivity and heat capacity measurements
      to show that also type II CH with M = cyclobutanone (CB) collapses on isothermal
      pressurization and undergoes a similar, weak, glass transition upon heating at 1
      GPa. Furthermore, we reveal for both THF CH and CB CH a second, much more
      pronounced, glass transition at temperatures above the thermally weak glass
      transition on heating in the 0.2-0.7 GPa range. This result suggests the general
      occurrence of two glass transitions in water-rich (94 mol %) pressure-collapsed
      CHs. Because of a large increase in dielectric permittivity concurrently as the
      weak heat capacity increase, the first glass transition must be due to kinetic
      unfreezing of water molecules. The thermal features of the second glass
      transition, measured on isobaric temperature cycling, are typical of a glass
      liquid-glass transition, which suggests that pressure-amorphized CHs transform
      reversibly to liquids.

PMID- 29584947
TI  - Metal Nanoparticles Embedded in Cellulose Nanocrystal Based Films: Material
      Properties and Post-use Analysis.
AB  - The dispersion of nanoparticles having different size-, shape-, and composition
      dependent properties is an exciting approach to design and synthesize
      multifunctional materials and devices. This work shows a detailed investigation
      of the preparation and properties of free-standing nanocomposite films based on
      cellulose nanocrystals (CNC) loaded with three different types of metal
      nanoparticles. CNC-based nanocomposites having zinc oxide (ZnO), titanium dioxide
      (TiO2), and silver oxide (Ag2O) have been obtained through evaporation-induced
      self-assembly (EISA) in acqueous solution. Morphological and optical
      characteristics, chemical properties, wettability, and antimicrobial assays of
      the produced films were conducted. Furthermore, disintegrability in composting
      condition of CNC based nanocomposites was here investigated for the first time.
      The morphological observations revealed the formation of a chiral nematic
      structure with uniformly distributed nanoparticles. The bionanocomposite films
      based on the metal nanoparticles had effective antimicrobial activity, killing
      both Escherichia coli RB ( E. coli RB) and Staphylococcus aureus 8325-4 ( S.
      aureus 8325-4). The simplicity method of film preparation, the large quantity of
      cellulose in the world, and the free-standing nature of the nanocomposite films
      offer highly advantageous characteristics that can for the new development of
      multifunctional materials.

PMID- 29584948
TI  - Air-Stable Room-Temperature Mid-Infrared Photodetectors Based on hBN/Black
      Arsenic Phosphorus/hBN Heterostructures.
AB  - Layered black phosphorus (BP) has attracted wide attention for mid-infrared
      photonics and high-speed electronics, due to its moderate band gap and high
      carrier mobility. However, its intrinsic band gap of around 0.33 electronvolt
      limits the operational wavelength range of BP photonic devices based on direct
      interband transitions to around 3.7 MUm. In this work, we demonstrate that black
      arsenic phosphorus alloy (b-As xP1- x) formed by introducing arsenic into BP can
      significantly extend the operational wavelength range of photonic devices. The as
      fabricated b-As0.83P0.17 photodetector sandwiched within hexagonal boron nitride
      (hBN) shows peak extrinsic responsivity of 190, 16, and 1.2 mA/W at 3.4, 5.0, and
      7.7 MUm at room temperature, respectively. Moreover, the intrinsic
      photoconductive effect dominates the photocurrent generation mechanism due to the
      preservation of pristine properties of b-As0.83P0.17 by complete hBN
      encapsulation, and these b-As0.83P0.17 photodetectors exhibit negligible
      transport hysteresis. The broad and large photoresponsivity within mid-infrared
      resulting from the intrinsic photoconduction, together with the excellent long
      term air stability, makes b-As0.83P0.17 alloy a promising alternative material
      for mid-infrared applications, such as free-space communication, infrared
      imaging, and biomedical sensing.

PMID- 29584949
TI  - A Chemical Probe for Protein Crotonylation.
AB  - Protein lysine crotonylation has emerged as an important post-translational
      modification (PTM) in the regulation of gene transcription through epigenetic
      mechanisms. Here we introduce a chemical probe, based on a water-soluble
      phosphine warhead, which reacts with the crotonyl modification. We show that this
      reagent is complementary to antibody-based tools allowing detection of endogenous
      cellular proteins such as histones carrying the crotonylation PTM. The tool is
      also used to show that the histone acylation activity of the transcriptional
      coactivator, p300, can be activated by pre-existing lysine crotonylation through
      a positive feedback mechanism. This reagent provides a versatile and sensitive
      probe for the analysis of this PTM.

PMID- 29584950
TI  - Does Soluble Mn(III) Oxidant Formed in Situ Account for Enhanced Transformation
      of Triclosan by Mn(VII) in the Presence of Ligands?
AB  - In previous studies, we interestingly found that several ligands (e.g.,
      pyrophosphate, nitrilotriacetate, and humic acid) could significantly accelerate
      the oxidation rates of triclosan (TCS; the most widely used antimicrobial) by
      aqueous permanganate (Mn(VII)) especially at acid pH, which was ascribed to the
      contribution of ligand-stabilized Mn(III) (defined Mn(III)L) formed in situ as a
      potent oxidant. In this work, it was found that the oxidation of TCS by Mn(III)L
      resulted in the formation of dimers, as well as hydroxylated and quinone-like
      products, where TCS phenoxy radical was likely involved. This transformation
      pathway distinctly differed from that involved in Mn(VII) oxidation of TCS, where
      2,4-dichlorophenol (DCP) was the major product with a high yield of ~80%.
      Surprisingly, we found that the presence of various complexing ligands including
      pyrophosphate, nitrilotriacetate, and humic acid, as well as bisulfite slightly
      affected the yields of DCP, although they greatly enhanced the oxidation kinetics
      of TCS by Mn(VII). This result could not be reasonably explained by taking the
      contribution of Mn(III)L into account. Comparatively, the degradation of TCS by
      manganese dioxide (MnO2) was also greatly enhanced in the presence of these
      ligands with negligible formation of DCP, which could be rationalized by the
      contribution of Mn(III)L. In addition, it was demonstrated that DCP could not be
      generated from Mn(VII) oxidation of unstable phenoxy radical intermediates and
      stable oxidation products formed from TCS by Mn(III)L. These findings indicate
      that manganese intermediates other than Mn(III) are likely involved in the
      Mn(VII)/TCS/ligand systems responsible for the high yields of DCP product.

PMID- 29584951
TI  - Reversible Valence Photoisomerization between Closed-Shell Quinoidal and Open
      Shell Biradical Forms.
AB  - We report here a kinetic study on the thermal equilibrium process between the
      biradical form and the quinoidal form starting from the singlet biradical form
      alone. A photochromic phenoxyl-imidazolyl radical complex repeatedly generates
      biradical species upon UV light irradiation, and the following thermal
      equilibrium process responsible for valence isomerization from the open-shell
      singlet biradical to the closed-shell quinoidal form is observed in the
      microsecond time region. The thermodynamic parameters for the equilibrium process
      were determined for the first time by nanosecond laser flash photolysis. We also
      found that visible-light excitation to the equilibrium state causes valence
      photoisomerization from the quinoidal to the biradical form, which returns
      thermally to the quinoidal form.

PMID- 29584952
TI  - Pesticide Risks in Small Streams-How to Get as Close as Possible to the Stress
      Imposed on Aquatic Organisms.
AB  - The risks associated with pesticides in small streams remain poorly
      characterized. The challenges reside in understanding the complexities of (1) the
      highly dynamic concentration profiles of (2) several hundred active substances
      with (3) differing seasonality. The present study addressed these three
      challenges simultaneously. Five small streams in catchments under intensive
      agricultural land use were sampled using half-day composite samples from March to
      August 2015. Of 213 active substances quantified using liquid chromatography-high
      resolution mass spectrometry, a total of 128 was detected at least at one of the
      sites. Ecotoxicological acute and/or chronic quality criteria were exceeded for a
      total of 32 different active substances. The evaluation of risks over time
      revealed the necessity to evaluate the sequences of different active substances
      that are imposed on aquatic organisms. In contrast, a substance-specific
      perspective provides only a very limited assessment. Scenarios for reduction of
      either temporal resolution, number of substances or seasonal coverage were
      defined. It could be shown that risks can be underestimated by more than a factor
      of 10 in vulnerable catchments and that an increased temporal resolution is
      essential to cover acute risks but that a focused selection of substances is a
      possibility to reduce expenditures.

PMID- 29584953
TI  - Deoxyfluorination with Sulfonyl Fluorides: Navigating Reaction Space with Machine
      Learning.
AB  - Through fine-tuning of reagent and base structure, sulfonyl fluorides can
      efficiently fluorinate diverse classes of alcohols. We show that machine learning
      can map the intricate reaction landscape and enable accurate prediction of high
      yielding conditions for untested substrates.

PMID- 29584954
TI  - Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using
      Fluorescence-Lifetime-Imaging Microscopy.
AB  - Pharmaceutical scientists are increasingly interested in amorphous drug
      formulations especially because of their higher dissolution rates. Consequently,
      the thorough characterization and analysis of these formulations are becoming
      more and more important for the pharmaceutical industry. Here, fluorescence
      lifetime-imaging microscopy (FLIM) was used to monitor the crystallization of an
      amorphous pharmaceutical compound, indomethacin. Initially, we identified
      different solid indomethacin forms, amorphous and gamma- and alpha-crystalline,
      on the basis of their time-resolved fluorescence. All of the studied indomethacin
      forms showed biexponential decays with characteristic fluorescence lifetimes and
      amplitudes. Using this information, the crystallization of amorphous indomethacin
      upon storage in 60  degrees C was monitored for 10 days with FLIM. The progress
      of crystallization was detected as lifetime changes both in the FLIM images and
      in the fluorescence-decay curves extracted from the images. The fluorescence
      lifetime amplitudes were used for quantitative analysis of the crystallization
      process. We also demonstrated that the fluorescence-lifetime distribution of the
      sample changed during crystallization, and when the sample was not moved between
      measuring times, the lifetime distribution could also be used for the analysis of
      the reaction kinetics. Our results clearly show that FLIM is a sensitive and
      nondestructive method for monitoring solid-state transformations on the surfaces
      of fluorescent samples.

PMID- 29584955
TI  - A Common Mechanism Links Activities of Butyrate in the Colon.
AB  - Two biological activities of butyrate in the colon (suppression of proliferation
      of colonic epithelial stem cells and inflammation) correlate with inhibition of
      the activity of histone deacetylases. Cellular and biochemical studies of
      molecules similar in structure to butyrate, but different in molecular details
      (functional groups, chain-length, deuteration, oxidation level, fluorination, or
      degree of unsaturation), demonstrated that these activities were sensitive to
      molecular structure, and were compatible with the hypothesis that butyrate acts
      by binding to the Zn2+ in the catalytic site of histone deacetylases. Structure
      activity relationships drawn from a set of 36 compounds offer a starting point
      for the design of new compounds targeting the inhibition of histone deacetylases.
      The observation that butyrate was more potent than other short-chain fatty acids
      is compatible with the hypothesis that crypts evolved (at least in part), to
      separate stem cells at the base of crypts from butyrate produced by commensal
      bacteria.

PMID- 29584956
TI  - Interface Engineering in Quantum-Dot-Sensitized Solar Cells.
AB  - The unique properties of II-VI semiconductor nanocrystals such as superior light
      absorption, size-dependent optoelectronic properties, solution processability,
      and interesting photophysics prompted quantum-dot-sensitized solar cells (QDSSCs)
      as promising candidates for next-generation photovoltaic (PV) technology. QDSSCs
      have advantages such as low-cost device fabrication, multiple exciton generation,
      and the possibility to push over the theoretical power conversion efficiency
      (PCE) limit of 32%. In spite of dedicated research efforts to enhance the PCE,
      optimize individual solar cell components, and better understand the underlying
      science, QDSSCs have unfortunately not lived up to their potential due to
      shortcomings in the fabrication process and with the QDs themselves. In this
      feature article, we briefly discuss the QDSSC concepts and mechanisms of the
      charge carrier recombination pathways that occur at multiple interfaces, viz.,
      (i) metal oxide (MO)/QDs, (ii) MO/QDs/electrolyte, and (iii) counter electrode
      (CE)/electrolyte. The rational strategies that have been developed to
      minimize/block these charge recombination pathways are elaborated. The article
      concludes with a discussion of the present challenges in fabricating efficient
      devices and future prospects for QDSSCs.

PMID- 29584957
TI  - Oxidative C-C Bond Functionalization of Methylenecyclopropanes with Aldehydes for
      the Formation of 2-Acyl-3,4-dihydronaphthalenes.
AB  - A new FeCl2- and DTBP (di- tert-butyl peroxide)-promoted oxidative ring-opening
      and cyclization of methylenecyclopropanes with aldehydes for the synthesis of 2
      acyl-3,4-dihydronaphthalenes is presented. This oxidative cyclization reaction
      proceeds via a radical addition, ring-opening, and cyclization sequence
      facilitated by a Lewis acid, and it offers a practical and straightforward route
      for the oxidative cyclization of methylenecyclopropanes with an aromatic carbon
      and a C(sp2)-H bond by simultaneously forming two new carbon-carbon bonds.

PMID- 29585206
TI  - The Recursive Trek of Epigenetics from the Bench to the Bedside. Predictive
      Methylation Marks by the Dozen.

PMID- 29584958
TI  - Enantioselective Radical Cyclization for Construction of 5-Membered Ring
      Structures by Metalloradical C-H Alkylation.
AB  - Radical cyclization represents a powerful strategy for construction of ring
      structures. Traditional radical cyclization, which is based on radical addition
      as the key step, necessitates the use of unsaturated substrates. Guided by the
      concept of metalloradical catalysis, a different mode of radical cyclization that
      can employ saturated C-H substrates is demonstrated through the development of a
      Co(II)-based system for catalytic activation of aliphatic diazo compounds for
      enantioselective radical alkylation of various C(sp3)-H bonds. It allows for
      efficient construction of chiral pyrrolidines and other valuable 5-membered
      cyclic compounds. This alternative strategy of radical cyclization provides a new
      retrosynthetic paradigm to prepare five-membered cyclic molecules from readily
      available open-chain aldehydes through the union of C-H and C=O elements for C-C
      bond formation.

PMID- 29585642
TI  - How to Detect a Cuckoo Egg: A Signal-Detection Theory Model for Recognition and
      Learning.
AB  - This article presents a model of egg rejection in cases of brood parasitism. The
      model is developed in three stages in the framework of signal-detection theory.
      We first assume that the behavior of host females is adapted to the relevant
      parameters concerning the appearance of the eggs they lay. In the second stage,
      we consider the possibility that females make perceptual errors. In the final
      stage, females must learn to recognize their own eggs through an imprinting
      process. The model allows us to make a number of predictions concerning the egg
      types that should be rejected in different circumstances: egg rejection should
      increase as the parasitism rate increases and egg mimicry deteriorates; host
      females' erroneous ejection of their own eggs should be expected for intermediate
      levels of egg mimicry but not for very good or very poor mimicry; host females
      would benefit most from learning to recognize their own eggs when individual
      variability in egg characteristics is much lower than the population variability;
      and, when egg mimicry is poor or individual variability is very low, females
      should attempt to imprint on the first egg they lay, before they can be
      parasitized, but, when mimicry is good and individual variability is relatively
      high, females must use an extended learning phase. The model provides a framework
      to study how the enigmatic acceptance of parasitic eggs can be explained by
      adaptive discrimination mechanisms.

PMID- 29585643
TI  - Spatial Moment Equations for Plant Competition: Understanding Spatial Strategies
      and the Advantages of Short Dispersal.
AB  - A plant lineage can compete for resources in a spatially variable environment by
      colonizing new areas, exploiting resources in those areas quickly before other
      plants arrive to compete with it, or tolerating competition once other plants do
      arrive. These specializations are ubiquitous in plant communities, but all three
      have never been derived from a spatial model of community dynamics-instead, the
      possibility of rapid exploitation has been either overlooked or confounded with
      colonization. We use moment equations, equations for the mean densities and
      spatial covariance of competing plant populations, to characterize these
      strategies in a fully spatial stochastic model. The moment equations predict
      endogenous spatial pattern formation and the efficacy of spatial strategies under
      different conditions. The model shows that specializations for colonization,
      exploitation, and tolerance are all possible, and these are the only possible
      spatial strategies; among them, they partition all of the endogenous spatial
      structure in the environment. The model predicts two distinct short-dispersal
      specializations where parents disperse their offspring locally, either to exploit
      empty patches quickly or to fill patches to exclude competitors.

PMID- 29585644
TI  - Scale-Invariant or Scale-Dependent Behavior of the Link Density Property in Food
      Webs: A Matter of Sampling Effort?

PMID- 29585645
TI  - The Cost of Compensation.

PMID- 29585646
TI  - Allometry of Constitutive Defense: A Model and a Comparative Test with Tree Bark
      and Fire Regime.
AB  - In a simulation model, the relative advantage of negative versus positive
      allometry of defense, that is, early versus delayed defensive investment, depends
      on the forms of the relationships between body size and growth, body size and
      mortality deterrence, and defense size and mortality deterrence. Positive
      allometry is favored by strongly sigmoidal growth, a strongly convex body
      size/deterrence relationship, and a concave defense-size/deterrence relationship.
      Rapid early growth, a weakly convex body-size/deterrence relationship, and a
      convex defense-size/deterrence relationship favor negative allometry. The model
      is tested by comparing, among Pinus and Quercus species, measured intraspecific
      bark allometry with a predicted ranking of bark allometry along the negative
      positive continuum. The ranking is based on the forms of body-size/deterrence and
      defense-size/deterrence relationships expected in each species' typical habitat
      given the fire regime and canopy type. This predicted ranking of bark allometry
      is significantly correlated with measured bark allometry. Negative bark allometry
      and thick sapling bark are associated with habitats characterized by frequent low
      intensity fire and relatively open canopies. Fire-resilient Pinus spp. and
      species of infrequently burned, closed-canopy forests tend to have positive bark
      allometry and thin sapling bark.

PMID- 29585647
TI  - Temporal Variation in Danger Drives Antipredator Behavior: The Predation Risk
      Allocation Hypothesis.
AB  - The rapid response of animals to changes in predation risk has allowed behavioral
      ecologists to learn much about antipredator decision making. A largely
      unappreciated aspect of such decision making, however, is that it may be
      fundamentally driven by the very thing that allows it to be so readily studied:
      temporal variation in risk. We show theoretically that temporal variability in
      risk leaves animals with the problem of allocating feeding and antipredator
      efforts across different risk situations. Our analysis suggests that an animal
      should exhibit its greatest antipredator behavior in high-risk situations that
      are brief and infrequent. An animal should also allocate more antipredator effort
      to high-risk situations and more feeding to low-risk situations, with an increase
      in the relative degree of risk in high-risk situations. However, the need to feed
      leaves an animal with little choice but to decrease its allocation of
      antipredator effort to high-risk situations as they become more frequent or
      lengthy; here, antipredator effort in low-risk situations may drop to low levels
      as an animal allocates as much feeding as possible to brief periods of low risk.
      These conclusions hold under various scenarios of interrupted feeding, state
      dependent behavior, and stochastic variation in risk situations. Our analysis
      also suggests that a common experimental protocol, in which prey animals are
      maintained under low risk and then exposed to a brief "pulse" of high risk, is
      likely to overestimate the intensity of antipredator behavior expected under
      field situations or chronic exposure to high risk.

PMID- 29585648
TI  - Balanced Polymorphisms and the Evolution of Dominance.
AB  - We explore the evolution of dominance at polymorphisms maintained either by
      overdominant selection or by migration-selection balance. At such balanced
      polymorphisms, heterozygotes remain at appreciable frequencies over long periods
      of time, allowing extensive modification of dominance to occur. The strength of
      selection favoring a modifier of dominance is roughly proportional to the
      probability that a modifier allele is found in a heterozygote at the locus
      subject to balancing selection times the heterozygote fitness increase caused by
      the modifier. Using a two-locus model, we elucidate the interesting ways in which
      recombination and migration cause departures from this rough expectation. For
      example, with overdominance, a genetic association with the rarest allele favors
      a modifier that increases heterozygote fitness because the modifier occurs more
      often in heterozygotes. With migration-selection balance, dominance evolves more
      readily in patches experiencing the strongest selection. We also find that, while
      there are more heterozygotes in sink populations (which have higher rates of
      immigration than emigration), selection for dominance in sink and source
      populations is nearly equal because sink populations make a lower genetic
      contribution to future generations. We conclude that the evolution of dominance
      is likely to occur whenever polymorphism is maintained by either overdominance or
      migration.

PMID- 29585730
TI  - Musculoskeletal Screening Tests and Bony Hip Morphology Cannot Identify Male
      Professional Soccer Players at Risk of Groin Injuries: A 2-Year Prospective
      Cohort Study.
AB  - BACKGROUND: Musculoskeletal hip/groin screening tests are commonly performed to
      detect at-risk individuals. Bony hip morphology is considered a potential
      intrinsic risk factor but has not been examined prospectively. PURPOSE: To
      evaluate the association between intrinsic risk factors identified from
      musculoskeletal and radiographic screening tests and hip/groin injuries leading
      to time loss from training and/or match play in professional male soccer players.
      STUDY DESIGN: Prospective cohort study; Level of evidence, 2. METHODS: Male
      professional soccer players, aged >=18 years, underwent screening specific for
      hip/groin pain during 2 consecutive seasons of the Qatar Stars League. The
      screening battery included pain provocation, range of motion, and strength tests
      as well as a hip radiographic examination. The radiographic examination included
      an anteroposterior pelvic view and 45 degrees  Dunn view, with bony hip
      morphology determined using quantitative methods. Time-loss (>=1 day) hip/groin
      injuries and individual player exposure (training and match play) were recorded
      prospectively, and injuries were categorized as adductor-related, inguinal
      related, iliopsoas-related, pubic-related, or hip-related groin pain, or "other,"
      as recommended in the Doha agreement. We calculated hazard ratios (HRs) from
      univariate and multivariate Cox regression models to assess the relationship
      between potential risk factors and hip/groin injuries. RESULTS: There were 438
      players, completing 609 player seasons, and 113 hip/groin injuries that met the
      criteria for inclusion, with 85 injuries categorized as adductor-related. The
      proportion of players with bony morphological variants was the following: cam,
      71%; pincer, 5%; and acetabular dysplasia, 13%. Previous hip/groin injuries (HR,
      1.8; 95% CI, 1.2-2.7) and eccentric adduction strength were associated with the
      risk of hip/groin injuries. Higher (>1 SD above the mean) than normal eccentric
      adduction strength was associated with an increased risk for all hip/groin
      injuries (HR, 1.6; 95% CI, 1.0-2.5). Lower (<1 SD below the mean) than normal
      eccentric adduction strength was associated with an increased risk for adductor
      related injuries (HR, 1.7; 95% CI, 1.0-3.0). No other musculoskeletal screening
      test or bony hip morphology variables were associated with the injury risk.
      CONCLUSION: Previous groin injuries and eccentric adduction strength were
      associated with the risk of groin injuries. However, these associations were not
      strong enough to identify an "at-risk" individual, and therefore, musculoskeletal
      screening tests were not useful to dictate individualized prevention strategies.
      Bony hip morphology was not associated with the risk of groin injuries.

PMID- 29585797
TI  - Erratum.

PMID- 29585968
TI  - Inequality and the Directionality of History.
AB  - I argue that history is genealogy and succession in an economic context of
      interactions among participants. Inequality is a ubiquitous property of economic
      interaction among responsive, metabolizing entities. The prevailing party tends
      to be larger, to have a higher productivity or metabolism, to engage in a larger
      number of interactions, and to perform more functions at a higher level. The
      crucial economic consequence of inequality is that prevailing entities and the
      conditions they create disproportionately influence the economy as a whole. This
      leads to a pervasive increase in energy flux, both globally and per capita, among
      economic dominants, observable in the history of life as well as in the
      development of the human economy. Unpredictable disturbances such as mass
      extinctions temporarily reverse this trend. Comparative studies of the biotas of
      islands and of large land masses point to limitations on the evolution of energy
      intensive dominants. Because entities with a large economic domain typically
      restrict rather than eliminate subordinates, the trend toward increasing energy
      flux will rarely be expressed within individual clades. History's directionality
      is imposed by effects of energy-intensive dominants on the distribution and
      characteristics of all other participants in the economies they help to fashion.

PMID- 29585927
TI  - Neutrophil activation in response to monomeric myeloperoxidase.
AB  - Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also regulate
      cellular functions via its nonenzymatic effects. Mature active MPO isolated from
      normal human neutrophils is a 145 kDa homodimer, which consists of 2 identical
      protomers, connected by a single disulfide bond. By binding to CD11b/CD18
      integrin, dimeric MPO induces neutrophil activation and adhesion augmenting
      leukocyte accumulation at sites of inflammation. This study was performed to
      compare the potency of dimeric and monomeric MPO to elicit selected neutrophil
      responses. Monomeric MPO (hemi-MPO) was obtained by treating the dimeric MPO by
      reductive alkylation. Analysis of the crucial signal transducer, intracellular
      Ca2+, showed that dimeric MPO induces Ca2+ mobilization from the intracellular
      calcium stores of neutrophils and influx of extracellular Ca2+ whereas the effect
      of monomeric MPO on Ca2+ increase in neutrophils was less. It was also shown that
      monomeric MPO was less efficient than dimeric MPO at inducing actin cytoskeleton
      reorganization, cell survival, and neutrophil degranulation. Furthermore, we have
      detected monomeric MPO in the blood plasma of patients with acute inflammation.
      Our data suggest that the decomposition of dimeric MPO into monomers can serve as
      a regulatory mechanism that controls MPO-dependent activation of neutrophils and
      reduces the proinflammatory effects of MPO.

PMID- 29585969
TI  - Sperm Displacement in the Yellow Dung Fly, Scatophaga stercoraria: An
      Investigation of Male and Female Processes.
AB  - Despite the ubiquity with which patterns of sperm utilization have been studied,
      the mechanisms underlying fertilization in insects are far from clear. One well
      studied system is the yellow dung fly, in which the last male's ejaculate is
      thought to displace rival sperm from the female's sperm stores. Here we follow
      the movement of the copulating male's ejaculate through the female's reproductive
      tract using males labeled with different radioisotopes. We find that males
      ejaculate into the bursa copulatrix and that male-1 sperm are displaced from the
      spermathecae during copulation. The increase in male-2 ejaculate in the
      spermathecae matches the pattern of male-2 fertilization gain, indicating that
      only spermathecal sperm are utilized at fertilization. Previously we have
      analyzed this system with a direct model of sperm displacement in which the male
      displaces rival sperm from the spermathecae. The data, and morphology of the
      female, clearly preclude such a mechanism. Here we contrast this model with a new
      indirect model, in which the female facilitates displacement by exchange of sperm
      from the bursa copulatrix to the spermathecae. The two models give equivalent
      fits to the observed sperm utilization patterns because the rate of sperm
      transfer into the bursa copulatrix greatly exceeds the rate of sperm exchange
      with the spermathecae so that the concentration of the first male's sperm in the
      bursa remains considerably lower than that of the second male. These analyses
      provide a quantitative attempt to incorporate female processes into the analysis
      of sperm utilization patterns in insects.

PMID- 29585970
TI  - Learning, Host Fidelity, and the Stability of Host-Parasitoid Communities.
AB  - Simple models of host-parasitoid interactions show that a polyphagous parasitoid
      tends to drive extinct all but the most fecund of its hosts. Coexistence requires
      a mechanism by which hosts with lower fecundity can increase when rare. We
      explore how recently discovered parasitoid learning behavior can contribute to
      species coexistence. On emergence as adults, parasitoids learn chemical cues
      associated with their natal host and hence are more likely to locate and to
      oviposit in hosts of the same species. For two models incorporating different
      assumptions about parasitoid searching, we derive conditions for the strength of
      host fidelity that permits a feasible multihost equilibrium and argue that this
      equilibrium is stable whenever the corresponding single-host equilibria are
      stable.

PMID- 29585971
TI  - Accounting for Mode of Speciation Increases Power and Realism of Tests of
      Phylogenetic Asymmetry.
AB  - Tree symmetry is crucial to the investigation of evolutionary processes,
      particularly adaptive radiation. Testing a phylogeny for asymmetry requires a
      null model; the most accepted to date is the Markov (random branching) model,
      which assumes that speciation is instantaneous and that all species have an equal
      and independent chance of speciation. Such assumptions result in a high
      probability of asymmetric trees (which makes tests of asymmetry weak) and may be
      unrealistic. Subsequent modification of this model incorporated parameters
      conforming to diversification by peripheral-isolates speciation, producing trees
      that were more symmetric than those generated under the Markov model. Our
      reanalysis of these data, and remodeling with a greater number of replicates,
      shows that differences between the original Markov and modified models may have
      been exaggerated: different measures show that initial increases in tree symmetry
      under peripheral-isolates speciation are transient; symmetry on small scales
      actually decreases when the process of speciation requires a significant fraction
      of the average time between speciation events. The peripheral-isolates mode of
      speciation is compared with a vicariant mode, which shows steadily increasing
      symmetry on all scales. In cases where vicariant speciation has been common, use
      of a vicariant-based null model in tests of phylogenetic asymmetry is appropriate
      and will provide greater statistical power.

PMID- 29585972
TI  - The Influence of Plant and Herbivore Characteristics on the Interaction between
      Induced Resistance and Herbivore Population Dynamics.
AB  - Induced plant resistance may contribute to regulating or driving fluctuations in
      insect herbivore populations. However, experimental demonstrations of induced
      resistance affecting long-term herbivore population dynamics are lacking, and few
      models find that induced resistance drives cycles in herbivore populations. Here
      a simulation model is used to explore the influence of characteristics of the
      plant-herbivore system on the likelihood that induced resistance can regulate or
      drive cycles in herbivore populations. Results of this model suggest that induced
      resistance may cause fluctuations in herbivore populations under more conditions
      than previously thought. The model incorporates parameters for the timing and
      strength of induced resistance and for herbivore mobility and host-plant
      selectivity. Results are presented for two configurations of the model: forest
      (many herbivore generations per plant generation) and crop (few herbivore
      generations per plant generation). In simulations of this model, induced
      resistance in the absence of other density-dependent factors can regulate
      herbivore populations. Induced resistance can also drive fluctuations in
      herbivore populations when there is a time lag between damage and the onset of
      induced resistance. The time lag required to cause fluctuations depends on
      characteristics such as the strength of induced resistance and the mobility of
      the herbivore.

PMID- 29585973
TI  - Predator Migration Decisions, the Ideal Free Distribution, and Predator-Prey
      Dynamics.
AB  - The aim of the present work is to analyze the influence of optimal predator
      emigration decisions that can lead to the ideal free distribution (IFD) on the
      stability of predator-prey systems. The assumption of optimal decisions is then
      relaxed to analyze the possible influence of different degrees of deviation from
      the IFD. The first migration rule we analyze is based on the marginal-value
      theorem and assumes perfect knowledge of capture rate in the patch of residence
      and in the environment as a whole. When migration rates are high, this rule leads
      the predator population to the IFD. The results suggest that under these
      conditions predator migration plays no major role in the stability of the system.
      This is so because the systems naturally merge into a single patch. This result
      is independent of the particular functional response used. The other two rules we
      analyze take into account lower migration rates, the limitations in making
      optimal decisions by predators, and the possible constraints in the assessment of
      intake rate in the different patches. The results suggest that the processes that
      hinder the convergence of the populations to the IFD might make a major
      contribution to the stability of the system.

PMID- 29585974
TI  - Interacting Phenotypes and the Evolutionary Process. II. Selection Resulting from
      Social Interactions.
AB  - Social interactions often affect the fitness of interactants. Because of this,
      social selection has been described as a process distinct from other forms of
      natural selection. Social selection has been predicted to result in different
      evolutionary dynamics for interacting phenotypes, including rapid or extreme
      evolution and evolution of altruism. Despite the critical role that social
      selection plays in theories of social evolution, few studies have measured the
      force of social selection or the conditions under which this force changes. Here
      we present a model of social selection acting on interacting phenotypes that can
      be evaluated independently from the genetics of interacting phenotypes. Our model
      of social selection is analogous to covariance models of other forms of
      selection. We observe that an opportunity for social selection exists whenever
      individual fitness varies as a result of interactions with conspecifics. Social
      selection occurs, therefore, when variation in fitness due to interactions
      covaries with traits, resulting in a net force of selection acting on the
      interacting phenotypes. Thus, there must be a covariance between the phenotypes
      of the interactants for social selection to exist. This interacting phenotype
      covariance is important because it measures the degree to which a particular
      trait covaries with the selective environment provided by conspecifics. A variety
      of factors, including nonrandom interactions, behavioral modification during
      interactions, relatedness, and indirect genetic effects may contribute to the
      covariance of interacting phenotypes, which promotes social selection. The
      independent force of social selection (measured as a social selection gradient)
      can be partitioned empirically from the force of natural selection (measured by
      the natural selection gradient) using partial regression. This measure can be
      combined with genetic models of interacting phenotypes to provide insights into
      social evolution.

PMID- 29585975
TI  - Reproductive Skew in Multimember Groups.
AB  - Cooperative societies vary in the extent to which reproduction is skewed toward
      one or a few socially dominant animals. Many recent models attempt to explain
      this variation on the basis that a dominant who benefits from the presence of
      subordinates may offer them incentives, in the form of reproductive
      opportunities, to remain in the group. While most societies contain multiple
      members, however, these models have considered only the relationship between a
      dominant and a single subordinate or have assumed that all subordinates are
      identical. We develop an incentive-based evolutionary stable strategy model of
      reproductive skew in three-member groups, in which subordinates may vary in their
      opportunities for independent reproduction, their contribution to group
      productivity, and in their relatedness both to the dominant and to one another.
      Our model demonstrates that the conclusions of two-member models cannot all be
      generalized to larger groups. For example, relatedness among group members can
      influence whether or not the dominant does best to offer staying incentives to
      subordinates in a three-member, but not a two-member, group. Both the degree of
      skew and group stability depend on the relatedness between subordinates as well
      as on the relatedness of each to the dominant, and the incentives that each
      individual subordinate receives are influenced by the traits of the other.
      Whether such effects increase or decrease skew and group stability depends
      crucially on whether a third group member increases group productivity to a
      greater or lesser extent than the first.

PMID- 29586431
TI  - American Society of Naturalists.

PMID- 29586486
TI  - The toxic effect of Vu-Defr, a defensin from Vigna unguiculata seeds, on
      Leishmania amazonensis is associated with reactive oxygen species production,
      mitochondrial dysfunction, and plasma membrane perturbation.
AB  - Plant defensins are plant antimicrobial peptides that present diverse biological
      activities in vitro, including the elimination of Leishmania amazonensis. Plant
      defensins are considered promising candidates for the development of new drugs.
      This protozoan genus has great epidemiological importance and the mechanism
      behind the protozoan death by defensins is unknown, thus, we chose L. amazonensis
      for this study. The aim of the work was to analyze the possible toxic mechanisms
      of Vu-Defr against L. amazonensis. For analyses, the antimicrobial assay was
      repeated as previously described, and after 24 h, an aliquot of the culture was
      tested for viability, membrane perturbation, mitochondrial membrane potential,
      reactive oxygen species (ROS) and nitric oxide (NO) inductions. The results of
      these analyses indicated that after interaction with L. amazonensis, the Vu-Defr
      causes elimination of promastigotes from culture, membrane perturbation,
      mitochondrial membrane collapse, and ROS induction. Our analysis demonstrated
      that NO is not produced after Vu-Defr and L. amazonensis interaction. In
      conclusion, our work strives to help to fill the gap relating to effects caused
      by plant defensins on protozoan and thus better understand the mechanism of
      action of this peptide against L. amazonensis.

PMID- 29586541
TI  - The pathogenicity of Aspergillus fumigatus, drug resistance, and nanoparticle
      delivery.
AB  - The genus Aspergillus includes fungal species that cause major health issues of
      significant economic importance. These microorganisms are also the culprit for
      production of carcinogenic aflatoxins in grain storages, contaminating crops, and
      economically straining the production process. Aspergillus fumigatus is a very
      important pathogenic species, being responsible for high human morbidity and
      mortality on a global basis. The prevalence of these infections in
      immunosuppressed individuals is on the rise, and physicians struggle with the
      diagnosis of these deadly pathogens. Several virulence determinants facilitate
      fungal invasion and evasion of the host immune response. Metabolic functions are
      also important for virulence and drug resistance, since they allow fungi to
      obtain nutrients for their own survival and growth. Following a positive
      diagnostic identification, mortality rates remain high due, in part, to emerging
      resistance to frequently used antifungal drugs. In this review, we discuss the
      role of the main virulence, drug target, and drug resistance determinants. We
      conclude with the review of new technologies being developed to treat
      aspergillosis. In particular, microsphere and nanoparticle delivery systems are
      discussed in the context of improving drug bioavailability. Aspergillus will
      likely continue to cause problematic infections in immunocompromised patients, so
      it is imperative to improve treatment options.

PMID- 29586617
TI  - The Effects of Selection and Bottlenecks on Male Mating Success in Peripheral
      Isolates.

PMID- 29586618
TI  - Indirect Effects in an Experimentally Staged Invasion by a Major Predator.
AB  - We used a system of neighboring small islands with and without the lizard Anolis
      sagrei to stage a 7-yr experimental study of the effects of an invading species.
      Lizard propagules were introduced to four islands, randomly selected from eight
      that lacked lizards naturally. Four other islands where lizards occurred
      naturally constituted a third treatment. We examined possible lizard indirect
      effects on the commonest shrub (via its arthropod herbivores), two sizes of
      aerial arthropods, and hymenopteran parasitoids. Lizards reduced leaf damage;
      moreover, during the middle years of the experiment, damage was less on
      introduction islands than on islands having lizards naturally. Lizards increased
      the number of small aerial arthropods but had no effect on large aerial
      arthropods; the full effect on small arthropods was only evident near the end of
      the experiment. Lizard introduction increased the number of hymenopteran
      parasitoids at the end of the experiment; however, only islands having lizards
      naturally had significantly more parasitoids than no-lizard islands summed over
      the long term. In contrast to the indirect effects, the mostly direct effect of
      lizards on spiders was very strong; introduction transformed spider density to
      that on natural lizard islands relatively rapidly and monotonically. In addition
      to demonstrating how an introduced vertebrate predator can affect food webs even
      down to the producer level, this study illustrates the greater strength and
      regularity of direct as opposed to indirect effects.

PMID- 29586619
TI  - Chick Begging Strategies in Relation to Brood Hierarchies and Hatching
      Asynchrony.
AB  - Altricial offspring solicit food by begging, and their parents feed them
      according to begging intensity, which has been shown to be positively related to
      offspring need. Parent-offspring genetic conflict calls for analyses of
      evolutionary stability, and various theoretical models have shown that stability
      is possible in the framework of handicap theory. The models predict that a
      negative relationship exists between offspring condition and begging and that
      offspring in poorer condition should be fed preferentially. However, these
      predictions depend on two unsatisfactory assumptions. First, they assume a
      monotonically decelerated relation between condition and fitness (this function
      is more likely to be sigmoid); second, they ignore physical competition between
      siblings, which is known to be important. We examined the significance of these
      issues by manipulating hatching asynchrony in broods of starlings Sturnus
      vulgaris, thus controlling competitive asymmetries between nest mates. We created
      broods with senior (older) and junior (younger) chicks and control broods with
      synchronous chicks. In field and laboratory experiments, we found that seniors
      begged less than juniors and controls, whereas juniors did not differ
      significantly from controls. However, seniors received more food from their
      parents and grew better than juniors or controls (hence, they were in better
      condition). These results violate the predictions of available theoretical models
      and, together with limitations in the universality of their assumptions, indicate
      that fundamental aspects of parent-offspring communication are not yet
      understood.

PMID- 29586620
TI  - Limiting Similarity, Species Packing, and System Stability for Hierarchical
      Competition-Colonization Models.
AB  - Hierarchical competition-colonization models have been used to explain limiting
      similarities among species, successional dynamics, and species loss under habitat
      destruction. This class of models assumes that there is an inverse relationship
      between competitive ability and colonization ability and that competitively
      superior species exclude competitively inferior species when both occupy the same
      site. This hierarchical model of performance trade-offs, however, exhibits some
      unusual behaviors in the high-diversity limit, including infinitesimally close
      species packing, pathologically slow dynamics, and fundamentally important
      regularities in trait-abundance relationships. In particular, under the condition
      of constant mortality across species, a 3/2-power-law relationship emerges
      between abundance and fecundity under infinite packing (abundance of a species
      with fecundity f is inversely proportional to f to the 3/2 power). In this
      article, we explore the high-diversity limit of the hierarchical competition
      colonization model, with particular emphasis on patterns of species packing,
      species-abundance relationships, and system stability. Because of the potential
      for pathologically slow dynamics following perturbations and infinitesimally
      close species packing in the high-diversity limit for this class of models, the
      models may need to be modified to include more realistic mechanisms governing the
      extent and timing of interspecific competitive exclusion in order to effectively
      capture the structure and dynamics of real-world ecosystems.

PMID- 29586621
TI  - Seasonal Sex Ratio Trend in the European Kestrel: An Evolutionarily Stable
      Strategy Analysis.
AB  - We present an evolutionarily stable strategy (ESS) model to analyze selection on
      seasonal variation in the brood sex ratio, as observed in several species of
      raptorial birds. The model is specifically tailored to the life history of the
      European kestrel, and it reflects the maturation time hypothesis, the idea that a
      seasonal sex ratio trend has evolved because of sex differences in the dependence
      of age of first breeding on date of birth. First we show how to derive a fitness
      function in the context of a seasonal environment. Model parameters are estimated
      from field data in order to derive quantitative predictions. Since little is
      known about constraints on sex ratio control in birds, we analyze three
      scenarios, each corresponding to a different strategy set. We consider a model
      without constraints on sex ratio control, a model where the sex ratio trend is
      constrained to be linear, and a mechanistic model incorporating a plausible
      mechanism of sex ratio control in birds. One of the models yields an ESS sex
      ratio trend that closely resembles the trend observed in the field. However, the
      predictions are very sensitive to the choice of strategy set. Moreover, the
      selective forces generated by sex differences in maturation are rather weak. In
      fact, the mechanistic model shows that seemingly negligible costs of sex ratio
      control may be sufficient to overcome the adaptive value of adjusting the sex
      ratio.

PMID- 29586622
TI  - Sperm Digestion and Reciprocal Sperm Transfer Can Drive Hermaphrodite Sex
      Allocation to Equality.
AB  - The intensity of sperm competition determines how much reproductive effort should
      be invested in sperm. One important factor affecting sperm competition in
      internally fertilizing organisms is the mating frequency of females, since it
      determines the extent of competition between ejaculates. In simultaneous
      hermaphrodites, energy spent on sperm has to be traded off against energy
      expended on ova production. By extending an existing model, we consider how the
      number of matings affects sperm competition and, thus, sex allocation in
      internally fertilizing simultaneous hermaphrodites. We then go on to explore the
      consequences of two common characteristics of hermaphroditic mating systems,
      namely, sperm digestion and reciprocal insemination. Since sperm digestion
      reduces the competitive ability of a given ejaculate, it selects for increased
      sperm investment. As a result, the amount of sperm digested and male allocation
      can enter a coevolutionary cycle in which both will increase up to the point of
      equal investment in male and female gametes and in high rates of digestion.
      Because of this high degree of sperm digestion, fitness through the male function
      becomes more dependent on the amount of resources invested in sperm than on the
      number of matings. As a result, sperm digestion reduces Bateman's principle.
      Hence, hermaphrodites with sperm digestion should be less likely to display
      traits that increase the number of matings. Once ejaculates are large and costly,
      animals insisting on reciprocal sperm transfer will be favored since they receive
      some compensation for their investment. Under reciprocity, an even higher
      investment in sperm is favored. This is the result of the compensation received
      in the form of the partner's ejaculate and a nuptial gift effect by increasing a
      partner's production of eggs.

PMID- 29586623
TI  - Timing of Estrus in Fallow Deer Is Adjusted to the Age of Available Mates.
AB  - The ability to manipulate the timing of ovulation should be a tool available to
      females during their choice of mates. Females should advance estrus when
      preferred males are available and delay estrus when only nonpreferred males are
      available. However, ovulation in some female mammals can be induced by the
      presence of males. Female estrus could then be either a result of a better
      stimulus provided by the preferred male or simply manipulation of estrus by the
      female to reflect her preference. Evidence is therefore required that female
      estrus coincides with the availability of preferred mating partners, that females
      actively choose among males, that avoidance of nonpreferred males results in a
      cost, and that nonpreferred males are in fact capable of reproduction. We
      observed two experimental groups of fallow deer, one with only socially mature
      males, and one with subadult but physiologically mature males. Females with
      mature males conceived earlier (13 of 15 gave birth) than females with subadult
      males. The former also conceived earlier than they did in the previous year,
      whereas the latter conceived later (13 of 14 gave birth) than in the previous
      year. Females avoided subadults more than mature males, and they lost more weight
      than females with mature males. Because subadult males are capable of
      reproduction, females not reproducing with them incur two costs: energetic loss
      and delayed reproduction. Given these costs, we suggest that females receive a
      benefit from not responding to the advances of young males that would outweigh
      these costs. This benefit may be to adjust ovulation to the availability of
      preferred mates.

PMID- 29586624
TI  - Does Body Size Optimization Result in Skewed Body Size Distribution on a
      Logarithmic Scale?

PMID- 29586625
TI  - The Evolution of Costly Resistance in Host-Parasite Systems.
AB  - Pairwise invadability analysis is used to examine the evolutionary dynamics of
      host resistance to microparasitic infection. A continuum of strains of the host
      differs in susceptibility to infection, with less susceptible strains paying a
      cost resulting in a lower intrinsic growth rate. With a combination of analytical
      and graphical pairwise invadability analysis, we show that the evolutionary
      outcome depends crucially on the shape of the constraint function between
      resistance and its assumed cost in intrinsic growth rates. When resistance is
      increasingly costly, a single evolutionarily stable strategy is predicted.
      Alternatively, with decreasingly costly resistance, we find that the hosts tend
      to be maximally resistant or not at all resistant. There are conditions under
      which dimorphism of both these types exists but intermediate resistances do not
      occur. Independently of the trade-off function used, we are always more likely to
      get resistant strains of the host when the carrying capacity of the host is high.
      The pathogenicity of the parasite is also important in determining the likelihood
      and degree of resistance.

PMID- 29586706
TI  - Exploring the Physiological Basis of Costs of Herbicide Resistance in Arabidopsis
      thaliana.
AB  - For some resistance traits identified in crop and weed species, plant
      physiologists have detailed knowledge of the mechanism of gene action that
      distinguishes the physiology of resistant and susceptible genotypes. Such
      information could be useful to those evolutionary biologists interested in
      coupling the genetics and physiology of resistance mutations with data on the
      relative fitness of resistant and susceptible genotypes. In previous work, we
      have shown that the lifetime seed production of chlorsulfuron-resistant
      Arabidopsis thaliana was substantially lower than that of susceptible plants, and
      here we explore potential physiological reasons for the fitness reduction. In
      addition, we highlight several methodological issues that are essential when
      using transgenic technology to explore fitness trade-offs.

PMID- 29586707
TI  - Mechanistic Analysis of Natural Selection and a Refinement of Lack's and
      Williams's Principles.
AB  - Results from several physiologically based manipulations were synthesized to
      investigate two selective trade-offs involving offspring number versus offspring
      quality and costs of reproduction in an annual lizard Uta stansburiana. Lifetime
      reproductive success of experimentally size-altered progeny was studied to
      address the offspring number and offspring quality trade-off. Causes of natural
      selection on adult reproductive costs were assessed with three complementary
      manipulations of clutch size, egg size, and total clutch mass. Selective trade
      offs between offspring size and number arose from two opposing episodes of
      directional selection. Fecundity selection favored female parents that laid large
      clutches of small offspring, but fecundity selection was balanced by survival
      selection that favored large offspring. Thus, the offspring number and quality
      trade-off had a strong stabilizing effect on mean egg size across generations.
      However, strength and direction of selection arising from adult reproductive
      costs varied among years. Because reproductive traits were heritable ([Formula:
      see text]), selection on adult reproduction led to a large evolutionary response
      to natural selection. Patterns of selection detected in natural phenotypic
      variation were largely corroborated by phenotypic manipulations. However,
      maturational costs of reproduction that were detected with phenotypic
      manipulations were missed by traditional selection analysis of natural phenotypic
      variation.

PMID- 29586708
TI  - Manipulative Approaches to Testing Adaptive Plasticity: Phytochrome-Mediated
      Shade-Avoidance Responses in Plants.
AB  - Phenotypic plasticity is often assumed to be adaptive, but this hypothesis has
      rarely been tested. To support the hypothesis, it is necessary to demonstrate
      that the phenotype induced in each relevant environment confers high fitness in
      that environment, relative to alternative phenotypes. Unfortunately, such tests
      are difficult to perform because plasticity prevents the expression of
      "inappropriate" phenotypes within each environment. Genetic and physiological
      manipulation can be used very effectively to extend the range of phenotypes
      within environments and thus provide powerful tools for testing the adaptive
      plasticity hypothesis. The expression of specific genes involved in cue
      perception or signal transduction can be altered by mutation or the introduction
      of transgenes, thus altering the plastic response of an organism to environmental
      cues. It is also possible to alter the cue itself or to manipulate the
      developmental response physiologically so as to obtain alternative phenotypes.
      The relative fitness of these alternative phenotypes can then be measured in each
      relevant environment. However, these techniques will be most useful when combined
      with techniques such as phenotypic selection analysis to identify the specific
      traits under selection in natural populations. We illustrate these approaches
      using phytochrome-mediated "shade avoidance" responses in plants as a model
      system. We review the genetic and physiological mechanisms underlying these
      responses, illustrate how genetic manipulation can elucidate their adaptive
      value, and discuss the use of physiological manipulation to measure natural
      selection on plasticity in the wild.

PMID- 29586709
TI  - Engineering Candidate Genes in Studies of Adaptation: The Heat-Shock Protein
      Hsp70 in Drosophila melanogaster.
AB  - One approach to elucidating the relationships among genes, traits, performance,
      and fitness is to choose genes of candidate evolutionary interest whose
      significance is well understood from in vitro and cellular studies and to explore
      the consequences of manipulating these genes in whole organisms in an
      evolutionary context. Ongoing research on Hsp70 in Drosophila exemplifies this
      candidate gene approach. The heat-shock protein Hsp70 was chosen for analysis
      because its biochemical phenotype (i.e., molecular chaperone activity),
      regulation, and encoding genes are well understood. Investigation of the thermal
      environment of Drosophila larvae in the wild and natural Hsp70 expression
      establishes an ecological context for the candidate gene. Engineering of the
      hsp70 genes via site-specific homologous recombination, expression off of a
      heterologous promoter, and expression of an innocuous protein off of the hsp70
      promoter show that Hsp70 can be sufficient for a significant component of
      inducible thermotolerance but can have deleterious consequences. Study of
      nonengineered variation in Hsp70 expression reveals that the genetically
      engineered effects have counterparts in nature. Thus, in complementary fashion,
      both genetic engineering and the more classical approaches of evolutionary
      biology each contribute essential insights to adaptation.

PMID- 29586710
TI  - Transgenes in the Analysis of Life Span and Fitness.
AB  - Drosophila P element-mediated transformation can be used to determine whether and
      how a specific gene contributes to demographic components of fitness. Motivated
      by the problem of senescence, researchers have applied this approach to genes
      thought to affect survival through processes of somatic maintenance. Cu/Zn
      superoxide dismutase and catalase reduce the flux of reactive oxygen molecules
      that are thought to be a central cause of aging. EF1alpha is a component of the
      protein synthesis machine; deterioration of this housekeeping function is a
      potential contributor to senescence. Molecular chaperones such as the heat shock
      protein hsp70 are multifunctional molecules that affect a cell's response to
      acute stress. In some models, senescence results from the cumulative effects of
      stress, and heat shock proteins may regulate the progress of this deterioration.
      Transformations with the candidate genes of these proteins were used in
      independent studies to measure the effect of overexpression on longevity;
      positive results were reported. Here, I discuss the robustness of these results.
      I use the studies of superoxide dismutase, catalase, and EF1alpha to illustrate
      how the mutagenic effects of inserts confound our interpretations. I present new
      data from a reported study of hsp70 overexpression to show how engineered
      constructs can be used to overcome mutagenic artifacts through the controlled
      excision of sequences or alleles. The data for hsp70 provide the first strong
      molecular evidence that somatic maintenance affects longevity. Finally, future
      potential uses of transformation with Drosophila are discussed. I consider how
      metabolic control theory predicts that overexpression of genes for enzymes of
      intermediary metabolism is not likely to produce analytically useful changes in
      components of fitness.

PMID- 29586711
TI  - Adaptation, Exaptation, and Constraint: A Hormonal Perspective.
AB  - We approach conceptual issues in evolutionary biology from an endocrinological
      perspective, noting that single hormones typically act on several target tissues
      and thereby mediate suites of correlated phenotypic traits. When several
      components of such a suite are beneficial, an important evolutionary question is
      whether all are adaptations or some are exaptations. The answer may depend on
      whether the traits arose in response to selection on variation in systemic levels
      of the hormone on variation in responsiveness of target tissues to invariant
      levels of the hormone. If the former, selection probably acted directly on fewer
      than all traits; beneficial traits arising indirectly would be exaptations. In
      contrast, multiple beneficial traits that arose out of independent changes in
      target-tissue sensitivity to invariant hormone levels could all be adaptations.
      Knowledge of specific hormonal mechanisms as well as of historical selective
      regimes will be necessary to draw such distinctions. Endocrine constraints on
      evolution can be studied experimentally by applying hormones systemically and
      measuring interdependent responses of beneficial and detrimental traits to
      selection (phenotypic engineering with hormones). Supposing that alteration of
      one trait in isolation would enhance fitness, cases in which the net effect of
      endocrine alteration of multiple traits is to depress fitness provide evidence
      for constraints. We briefly report results of recent studies employing hormonal
      manipulations, stressing our own work on the dark-eyed junco (Junco hyemalis:
      Emberizidae).

PMID- 29586931
TI  - Role of Consumers in Guideline Development Process.
AB  - Clinical practice guidelines (CPGs) inform patient care by providing
      recommendations based on a thorough examination of risks and benefits of medical
      care or intervention. With the ever-increasing importance placed on shared
      decision making, and because of the valuable perspective on patient-related
      topics and patient-centered outcomes, consumers of health care have been
      incorporated in the American Academy of Otolaryngology-Head and Neck Surgery
      Foundation CPG development process. Consumers bring a unique perspective and add
      transparency to the guideline development process. In addition, they are
      instrumental in formulating patient-friendly recommendations that are easier to
      understand. Studies that have been done to evaluate the role of consumers in the
      CPG development process found that consumers had a positive impact. In addition,
      studies report that consumers felt adequately prepared after appropriate training
      and education on the process. Further studies are needed to understand how to
      best engage, train, and educate consumers in future guidelines development.

PMID- 29587004
TI  - Developing a Phosphospecific IHC Assay as a Predictive Biomarker for
      Topoisomerase I Inhibitors.
AB  - Phosphorylation is the most extensively studied posttranslational modification of
      proteins. There are approximately 500 kinases known in the human genome. The
      kinase-activated pathways regulate almost every aspect of cell function and a
      deregulated kinase cascade leads to impaired cellular function. Impaired
      regulation of several kinase cascades, including the epidermal growth factor
      receptor (EGFR) pathway, leading to tumor pathogenesis, is well documented. Thus,
      a phosphospecific test with prognostic or predictive value was expected in
      oncology. However, no phosphospecific IHC test is used in oncology clinics. Human
      topoisomerase I (topoI) inhibitors, camptothecin and its analogues (CPT), are
      used extensively to treat various solid tumors. Depending on tumor type, the
      response rate is only 13-32%. We have demonstrated that the deregulated kinase
      cascade is at the core of CPT resistance. DNA-PKcs, a kinase central to the DNA
      double-strand break (DSB) response pathway, phosphorylates topoI at serine 10
      (topoI-pS10), and cells with higher basal levels of topoI-pS10 degrade topoI
      rapidly and are resistant to this class of drug. The higher basal level of topoI
      phosphorylation is due to continual activation of DNA-PKcs, and one potential
      mechanism of this pathway activation is failure of upstream effector phosphatases
      such as phosphatase and tensin homolog (PTEN). Based on this understanding, we
      have developed an IHC-based test (P-topoIDx) that can stratify the responder and
      non-responder patient population.

PMID- 29587045
TI  - Mean Rank, Equipercentile, and Regression Mapping of World Health Organization
      Quality of Life Brief (WHOQOL-BREF) to EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
      Utilities.
AB  - BACKGROUND: Existing methods to link preference-based and profile-based health
      related quality of life (HRQoL) questionnaires have their limitations. Hence, we
      developed a new mapping method (the mean rank method, MRM) and applied it to map
      the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) to the
      EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L). We then compared the new MRM with
      current methods; i.e., regression-mapped (OLS method) and equipercentile method
      (EPM). METHODS: Singapore residents, aged >=21 y, were recruited from the general
      population and 2 outpatient clinics in acute care hospitals. Performance of the
      MRM was evaluated using both simulation and split-sample validation ( n = 658 in
      training and n = 657 in validation samples). Using the training sample, we
      derived 3 sets of mapped EQ-5D-5L utilities based on MRM, OLS method and EPM.
      Using simulation and the validation sample, we compared the performance of the
      mapping methods in terms of distribution parameters, mean utility by strata,
      association with health covariates, and prediction errors at the individual
      level, among others. RESULTS: The WHOQOL-BREF Physical Health domain is the only
      domain significantly associated with EQ-5D-5L utilities. Simulation showed that
      MRM more accurately reproduced the variance and percentiles of the distribution
      of the observed utilities than did the OLS method or EPM. OLS method tended to
      underestimate the mean utility of good health states, overestimate the mean
      utility of poor health states, and underestimate the association with covariates.
      An analysis of validation sample gave similar results. CONCLUSION: In scenarios
      similar to the mapping of WHOQOL-BREF to the EQ-5D-5L, the MRM outperformed the
      OLS method and EPM in important-though not all-aspects. The simplicity and
      reproducibility of the MRM makes it an attractive alternative to current methods.

PMID- 29587047
TI  - Microsimulation Modeling for Health Decision Sciences Using R: A Tutorial.
AB  - Microsimulation models are becoming increasingly common in the field of decision
      modeling for health. Because microsimulation models are computationally more
      demanding than traditional Markov cohort models, the use of computer programming
      languages in their development has become more common. R is a programming
      language that has gained recognition within the field of decision modeling. It
      has the capacity to perform microsimulation models more efficiently than software
      commonly used for decision modeling, incorporate statistical analyses within
      decision models, and produce more transparent models and reproducible results.
      However, no clear guidance for the implementation of microsimulation models in R
      exists. In this tutorial, we provide a step-by-step guide to build
      microsimulation models in R and illustrate the use of this guide on a simple, but
      transferable, hypothetical decision problem. We guide the reader through the
      necessary steps and provide generic R code that is flexible and can be adapted
      for other models. We also show how this code can be extended to address more
      complex model structures and provide an efficient microsimulation approach that
      relies on vectorization solutions.

PMID- 29587086
TI  - Longitudinal Tracking of Sound Exposure and Hearing Aid Usage through Objective
      Data Logs.
AB  - Objective To use data-logging technology to objectively track and identify
      predictors of hearing aid (HA) usage and aided sound exposure. Study Design Case
      series with planned data collection. Setting Tertiary academic medical center.
      Subjects and Methods Individuals with HAs between 2007 and 2016 were included (N
      = 431; mean, 74.6 years; 95% CI, 73.1-76.0). Data-logging technology intrinsic to
      new-generation HAs was enabled to track usage and sound exposure. With
      multivariable linear regression, age, sex, number of audiology visits, duration
      of audiologic follow-up, pure tone average, and HA side were assessed as
      predictors of usage (hours/day) and aided sound exposure (dB-hours/day; ie,
      "dose" of sound per day). Results Mean follow-up was 319 days (95% CI, 277-360).
      Mean HA usage was 8.4 hours/day (95% CI, 8.0-8.8; N = 431). Mean aided sound
      exposure was 440 dB-hours/day (95% CI, 385-493; n = 110). HA use (beta < 0.001, P
      = .45) and aided sound exposure (beta = -0.006, P = .87) were both stable over
      time. HA usage was associated only with hearing loss level (pure tone average;
      beta = 0.030, P = .04). Aided sound exposure was associated only with duration of
      audiologic follow-up (beta = 0.100, P = .02). Conclusion While measurement of HA
      use has traditionally relied on subjective reporting, data logging offers an
      objective tool to longitudinally track HA use and sound exposure. We demonstrate
      the feasibility of using this potentially powerful research tool. Usage and sound
      exposure were stable among patients throughout the study period. Use was greater
      among subjects with greater hearing loss. Maximizing aided sound exposure might
      be possible through continued audiology follow-up visits.

PMID- 29587129
TI  - Musical Preferences Predict Personality: Evidence From Active Listening and
      Facebook Likes.
AB  - Research over the past decade has shown that various personality traits are
      communicated through musical preferences. One limitation of that research is
      external validity, as most studies have assessed individual differences in
      musical preferences using self-reports of music-genre preferences. Are
      personality traits communicated through behavioral manifestations of musical
      preferences? We addressed this question in two large-scale online studies with
      demographically diverse populations. Study 1 ( N = 22,252) shows that reactions
      to unfamiliar musical excerpts predicted individual differences in personality
      most notably, openness and extraversion-above and beyond demographic
      characteristics. Moreover, these personality traits were differentially
      associated with particular music-preference dimensions. The results from Study 2
      ( N = 21,929) replicated and extended these findings by showing that an active
      measure of naturally occurring behavior, Facebook Likes for musical artists, also
      predicted individual differences in personality. In general, our findings
      establish the robustness and external validity of the links between musical
      preferences and personality.

PMID- 29587128
TI  - Direct Analysis of Pathogenic Structures Affixed to the Tympanic Membrane during
      Chronic Otitis Media.
AB  - Objective To characterize otitis media-associated structures affixed to the
      mucosal surface of the tympanic membrane (TM) in vivo and in surgically recovered
      in vitro samples. Study Design Prospective case series without comparison.
      Setting Outpatient surgical care center. Subjects and Methods Forty pediatric
      subjects scheduled for tympanostomy tube placement surgery were imaged
      intraoperatively under general anesthesia. Postmyringotomy, a portable optical
      coherence tomography (OCT) imaging system assessed for the presence of any
      biofilm affixed to the mucosal surface of the TM. Samples of suspected microbial
      infection-related structures were collected through the myringotomy incision. The
      sampled site was subsequently reimaged with OCT to confirm collection from the
      original image site on the TM. In vitro analysis based on confocal laser scanning
      microscope (CLSM) images of fluorescence in situ hybridization-tagged samples and
      polymerase chain reaction (PCR) provided microbiological characterization and
      verification of biofilm activity. Results OCT imaging was achieved for 38 of 40
      subjects (95%). Images from 38 of 38 (100%) of subjects observed with OCT showed
      the presence of additional microbial infection-related structures. Thirty-four
      samples were collected from these 38 subjects. CLSM images provided evidence of
      clustered bacteria in 32 of 33 (97%) of samples. PCR detected the presence of
      active bacterial DNA signatures in 20 of 31 (65%) of samples. Conclusion PCR and
      CLSM analysis of fluorescence in situ hybridization-stained samples validates the
      presence of active bacteria that have formed into a middle ear biofilm that
      extends across the mucosal layer of the TM. OCT can rapidly and noninvasively
      identify middle ear biofilms in subjects with severe and persistent cases of
      otitis media.

PMID- 29587130
TI  - Astaxanthin counteracts the effects of heat shock on the maturation of bovine
      oocytes.
AB  - The cellular mechanisms induced by elevated temperature on oocytes are not fully
      understood. However, there is evidence that some of the deleterious effects of
      heat shock are mediated by a heat-induced increase in reactive oxygen species
      (ROS). In this context, carotenoid antioxidants might have a thermoprotective
      effect. Therefore, the objective of this study was to determine the role of
      astaxanthin (AST) on oocyte ROS production and on the redox profile and
      developmental competency of cumulus-oocyte complexes (COCs) after 14h heat shock
      (41 degrees C) during in vitro maturation (IVM). Exposure of oocytes to heat
      shock during IVM increased ROS and reduced the ability of the oocyte to cleave
      and develop to the blastocyst stage. However, 12.5 and 25nM astaxanthin rescued
      these negative effects of heat shock; astaxanthin counteracted the heat shock
      induced increase in ROS and restored oocyte developmental competency. There was
      no effect of astaxanthin on maturation medium lipid peroxidation or on
      glutathione peroxidase and catalase activity in oocytes and cumulus cells.
      However, astaxanthin stimulated superoxide dismutase (SOD) activity in heat
      shocked cumulus cells. In conclusion, direct heat shock reduced oocyte
      competence, which was restored by astaxanthin, possibly through regulation of ROS
      and SOD activity in oocytes and COCs.

PMID- 29587131
TI  - Task switching costs in preschool children and adults.
AB  - Past research investigating cognitive flexibility has shown that preschool
      children make many perseverative errors in tasks that require switching between
      different sets of rules. However, this inflexibility might not necessarily hold
      with easier tasks. The current study investigated the developmental differences
      in cognitive flexibility using a task-switching procedure that compared reaction
      times and accuracy in 4- and 6-year-olds with those in adults. The experiment
      involved simple target detection tasks and was intentionally designed in a way
      that the stimulus and response conflicts were minimal together with a long
      preparation window. Global mixing costs (performance costs when multiple tasks
      are relevant in a context), and local switch costs (performance costs due to
      switching to an alternative task) are typically thought to engage endogenous
      control processes. If this is the case, we should observe developmental
      differences with both of these costs. Our results show, however, that when the
      accuracy was good, there were no age differences in cognitive flexibility (i.e.,
      the ability to manage multiple tasks and to switch between tasks) between
      children and adults. Even though preschool children had slower reaction times and
      were less accurate, the mixing and switch costs associated with task switching
      were not reliably larger for preschool children. Preschool children did, however,
      show more commission errors and greater response repetition effects than adults,
      which may reflect differences in inhibitory control.

PMID- 29587132
TI  - Synthesis, biological evaluation, and docking studies of novel 5,6-diaryl-1,2,4
      triazine thiazole derivatives as a new class of alpha-glucosidase inhibitors.
AB  - A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized
      and characterized by 1H NMR and 13C NMR and evaluated for their alpha-glucosidase
      inhibitory activity. All tested compounds displayed good alpha-glucosidase
      inhibitory activity with IC50 values ranging between 2.85 +/- 0.13 and 14.19 +/-
      0.23 MUM when compared to the standard drug acarbose (IC50 = 817.38 +/- 6.27
      MUM). Compound 7i (IC50 = 2.85 +/- 0.13 MUM) exhibited the highest activity among
      this series of compounds. Molecular docking studies were carried out in order to
      investigate the binding mode of this class of compounds to alpha-glucosidase.
      This study showed that these 5,6-diaryl-1,2,4-triazine thiazole derivatives are a
      new class of alpha-glucosidase inhibitors.

PMID- 29587133
TI  - The role of Hedgehog signaling in cementoblast differentiation.
AB  - OBJECTIVE: It has been well known that Hedgehog (Hh) signaling plays an important
      role in bone development, however, its function in cementogenesis has not yet
      been reported. This study was intended to elucidate the role of Hh signaling in
      cementoblast differentiation. DESIGN: Expression changes of various Hh signaling
      components and levels of skeletogenic markers (alkaline phosphatase, osteocalcin,
      osteopontin) and osteogenic transcription factors (RUNX2, Osterix) by Hh
      signaling modulators during OCCM-30 cementoblast differentiation were determined
      by quantitative real-time reverse transcriptase polymerase chain reaction. To
      investigate effects of Hh signaling modulators on the mineralization of
      cementoblast, alkaline phosphatase and alizarin red S staining were used. Then,
      the interaction between Hh and BMP signaling during cementoblast differentiation
      was evaluated using co-treatment of BMP7 and Hh signaling modulators. RESULTS: We
      observed the consistent expression of Hh signaling molecules in the OCCM-30,
      which were up-regulated during cementoblast differentiation. We also found that
      the treatment of cells with Purmo, an Hh activator, enhanced cementoblast
      differentiation by increasing the mRNA expression of skeletogenic markers and
      osteogenic transcription factors, as well as increasing alkaline phosphate
      activity and mineralization capability. On the contrary, an Hh antagonist, like
      Cyclo, effectively inhibited cementoblast differentiation. Furthermore, BMP7
      promoted cementoblast differentiation through crosstalk with the Hh signaling.
      CONCLUSION: These results suggest that Hh signaling is involved in cementoblast
      differentiation, and Hh signaling molecules may therefore represent new
      therapeutic targets in periodontal treatment and regeneration.

PMID- 29587135
TI  - Clinical duration of eruption of deciduous teeth in Jordanian children: A cross
      sectional study.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical duration of
      eruption (CDE) for deciduous teeth in Jordanian children, from the moment of
      gingival emergence until functional occlusal contact. DESIGN: This cross
      sectional study included 1988 children (885 females, 1103 males) aged 1-45 months
      examined for deciduous tooth emergence. Through probit regression analysis (SPSS
      Version 16.0), the median ages of emergence (MAE) and of functional eruption
      (MAF) were calculated per tooth; time difference between the two events
      represented CDE in months. Mann Whitney U tests and two-tailed Spearman's
      bivariate correlation test were used to investigate sexual dimorphisms in CDE,
      and find relationships between MAE and CDE, respectively. Significance was set at
      P <= 0.05. RESULTS: The average CDE was (4.45 +/- 1.96) months; it was less in
      males (4.33 +/- 1.99) than in females (4.57 +/- 1.93) with no significant gender
      differences (P = 0.38). Longest and shortest CDE were for maxillary first molars
      and mandibular lateral incisors, respectively. None of the teeth showed
      statistically significant differences in CDEs between genders. In addition, there
      were insignificant positive moderate correlations between MAE and CDE (r = 0.60,
      0.52, P = 0.07, 0.12 for males and females, respectively). CONCLUSIONS: This
      study has established the first standards for CDE in deciduous teeth for
      Jordanian children with an average CDE (4.5 +/- 2, range 1.6-8 months). Some
      variations in CDE can be explained by variations in age of emergence however,
      variations in CDE were not related to gender. The deciduous dentition in
      Jordanians is in active state of eruption between approximately 8.2-32 months.

PMID- 29587134
TI  - Surface free energy of enamel treated with sodium hexametaphosphate, calcium and
      phosphate.
AB  - OBJECTIVE: This study evaluated the capacity of sodium hexametaphosphate (HMP) at
      different concentrations to alter the surface properties of dental enamel in
      order to increase calcium and phosphate adsorption. DESIGN: Bovine enamel blocks
      (4 mm * 4 mm, n = 144, 12/group) were divided: 0%; 0.25%; 0.5%; and 1% HMP,
      followed or not by application of solutions containing Ca or Ca-PO4, totaling 12
      groups. The treatments were performed for 2 min, and the surface free energy
      (mN/m) was calculated by measuring the contact angles of three probing liquids
      (deionized water, diiodomethane and ethylene glycol), which was used to determine
      the polar and nonpolar components of the enamel surface. Calcium (Ca), phosphate
      (PO4) and HMP in the solutions treatment solutions were analyzed before and after
      treatment. The data presented normal and homogeneous distribution and then were
      subjected to ANOVA, followed by Student-Newman Keuls' test (p < 0.05). RESULTS:
      The higher the% of HMP in the solutions, the greater HMP adsorption and more
      electron-donor sites on enamel surface were achieved (p < 0.05). Also, Ca
      adsorption was higher with increasing% HMP in the solutions (p < 0.05), which in
      turn reduced electron-donor sites on enamel surface. Increased Ca and PO4
      adsorption occurred at 0.5% and 1% HMP after treatment with Ca-PO4 solution,
      resulting in a less electron-donor sites on surface when compared to the other
      treatments (P < 0.05). CONCLUSIONS: HMP leads to a more electron-donor sites on
      enamel surface, what promotes greater adsorption of Ca and PO4 ions.

PMID- 29587136
TI  - XRD and solid state 13C-NMR evaluation of the crystallinity enhancement of 13C
      labeled bacterial cellulose biosynthesized by Komagataeibacter xylinus under
      different stimuli: A comparative strategy of analyses.
AB  - The production and crystallinity of 13C bacterial cellulose (BC) was examined in
      static culture of Komagataeibacter xylinus with different chemical and physical
      stimuli: the addition of NaCl or cloramphenicol as well as exposure to a magnetic
      field or to UV light. Crystalline BC biosynthesized under each stimulus was
      studied by XRD and solid state 13C NMR analyses. All treatments produced BC with
      enhanced crystallinity over 90% (XRD) and 80% (NMR) compared to the control (83
      and 76%, respectively) or to Avicel (77 and 62%, respectively). The XRD data
      indicated that the crystallite size was 80-85 A. Furthermore, changes on the
      allomorphs (Ialpha and Ibeta) ratio tendency of BC samples addressed to the
      stimuli were estimated using the C4 signal from 13C NMR data. These results
      showed a decrease of the allomorph Ialpha (3%) when BC was biosynthesized with UV
      light and chloramphenicol compared to control (58.79%). In contrast, the BC
      obtained with NaCl increased up to 60.31% of the Ialpha allomorph ratio.

PMID- 29587137
TI  - Synthesis and self-assembling properties of 4,6-O-benzylidene acetal protected D
      glucose and D-glucosamine beta-1,2,3-triazole derivatives.
AB  - Sugar based low molecular weight gelators (LMWGs) are useful small molecules that
      can form reversible supramolecular gels with many applications. Selective
      functionalization of common monosaccharides has resulted in several classes of
      effective LMWGs. Recently we found that certain peracetylated sugars containing
      anomeric triazole functional groups were effective gelators. In this study we
      synthesized two series of 4,6-O-benzylidene acetal protected beta-1,2,3-triazolyl
      glycoside of D-glucose and N-acetyl D-glucosamine derivatives and evaluated their
      self-assembling properties in a few solvents. Several gelators were obtained and
      the gelation properties of these compounds rely on the structures of the 4
      triazolyl substituents. Typically, alkyl derivatives resulted in effective
      gelation in organic solvents and aqueous mixtures of ethanol and dimethyl
      sulfoxide. But further acetylation of these compounds resulted in loss of
      gelation properties. The gels were characterized using optical microscopy,
      rheology, and FTIR spectroscopy. We also analyzed the molecular assemblies, using
      1H NMR spectroscopy to probe the influences of the hydroxyl, amide, and triazole
      functional groups. Naproxen was used as a model drug and it formed co-gels with
      compound 25 in DMSO water mixtures. Using UV spectroscopy, we found that naproxen
      was slowly released from the gel to aqueous solution. The general structure and
      gelation trend obtained here can be useful in designing sugar based biomaterials.
      We expect that further structural optimization can lead to more effective
      gelators that are compatible with different drug molecules for encapsulation and
      sustained release.

PMID- 29587138
TI  - Basal Cells in Lung Development and Repair.
AB  - Basal cells are an important stem cell lineage in many tissues, including the
      lung. In this issue of Developmental Cell, Yang et. al. (2018) find that basal
      cells emerge very early in lung development and that a subset of these
      contributes to the expansive epithelial wound response observed after influenza
      injury.

PMID- 29587139
TI  - Quality before Quantity: Inspecting CFTR.
AB  - CFTR biosynthesis is highly dynamic. In this issue of Developmental Cell,
      Okiyoneda et al. (2018) show that RFFL serves as a CFTR conformation scrutinizer
      at the plasma membrane. It recognizes misfolded CFTR proteins and marks them for
      degradation. This quality control mechanism may be explored to benefit cystic
      fibrosis patients.

PMID- 29587140
TI  - piRNA Rules of Engagement.
AB  - piRNAs are known to silence transposable elements, but not all piRNAs match
      transposon sequences. Recent studies from Shen et al. (2018) and Zhang et al.
      (2018) identify rules for piRNA target recognition in Caenorhabditis elegans.
      Permissive pairing rules allow targeting of essentially all germline mRNAs, while
      protective mechanisms prevent silencing self-genes.

PMID- 29587141
TI  - Exploring the Function of Dynamic Phosphorylation-Dephosphorylation Cycles.
AB  - Protein phosphorylation is a dynamic post-translational modification critical for
      biological responses. At the level of individual molecules, phosphorylation
      dynamics can have important functional implications, but this information is
      rarely quantified. We discuss how rapid phosphorylation-dephosphorylation cycles
      could underlie important signaling properties, including the ability to rapidly
      bind and release proteins.

PMID- 29587142
TI  - Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity.
AB  - We show that the loss or gain of transcription factor programs that govern
      embryonic cell-fate specification is associated with a form of tumor plasticity
      characterized by the acquisition of alternative cell fates normally
      characteristic of adjacent organs. In human non-small cell lung cancers,
      downregulation of the lung lineage-specifying TF NKX2-1 is associated with tumors
      bearing features of various gut tissues. Loss of Nkx2-1 from murine alveolar, but
      not airway, epithelium results in conversion of lung cells to gastric-like cells.
      Superimposing oncogenic Kras activation enables further plasticity in both
      alveolar and airway epithelium, producing tumors that adopt midgut and hindgut
      fates. Conversely, coupling Nkx2-1 loss with foregut lineage-specifying SOX2
      overexpression drives the formation of squamous cancers with features of
      esophageal differentiation. These findings demonstrate that elements of
      pathologic tumor plasticity mirror the normal developmental history of organs in
      that cancer cells acquire cell fates associated with developmentally related
      neighboring organs.

PMID- 29587143
TI  - A Golgi Lipid Signaling Pathway Controls Apical Golgi Distribution and Cell
      Polarity during Neurogenesis.
AB  - Phosphatidylinositol (PtdIns) transfer proteins (PITPs) stimulate PtdIns-4-P
      synthesis and signaling in eukaryotic cells, but to what biological outcomes such
      signaling circuits are coupled remains unclear. Herein, we show that two highly
      related StART-like PITPs, PITPNA and PITPNB, act in a redundant fashion to
      support development of the embryonic mammalian neocortex. PITPNA/PITPNB do so by
      driving PtdIns-4-P-dependent recruitment of GOLPH3, and likely ceramide transfer
      protein (CERT), to Golgi membranes with GOLPH3 recruitment serving to promote
      MYO18A- and F-actin-directed loading of the Golgi network to apical processes of
      neural stem cells (NSCs). We propose the primary role for PITP/PtdIns-4
      P/GOLPH3/CERT signaling in NSC Golgi is not in regulating bulk membrane
      trafficking but in optimizing apically directed membrane trafficking and/or
      apical membrane signaling during neurogenesis.

PMID- 29587144
TI  - Nutritional Control of Stem Cell Division through S-Adenosylmethionine in
      Drosophila Intestine.
AB  - The intestine has direct contact with nutritional information. The mechanisms by
      which particular dietary molecules affect intestinal homeostasis are not fully
      understood. In this study, we identified S-adenosylmethionine (SAM), a universal
      methyl donor synthesized from dietary methionine, as a critical molecule that
      regulates stem cell division in Drosophila midgut. Depletion of either dietary
      methionine or SAM synthesis reduces division rate of intestinal stem cells.
      Genetic screening for putative SAM-dependent methyltransferases has identified
      protein synthesis as a regulator of the stem cells, partially through a unique
      diphthamide modification on eukaryotic elongation factor 2. In contrast, SAM in
      nutrient-absorptive enterocytes controls the interleukin-6-like protein Unpaired
      3, which is required for rapid division of the stem cells after refeeding. Our
      study sheds light upon a link between diet and intestinal homeostasis and
      highlights the key metabolite SAM as a mediator of cell-type-specific starvation
      response.

PMID- 29587146
TI  - Pullout strength of standard vs. cement-augmented rotator cuff repair anchors in
      cadaveric bone.
AB  - BACKGROUND: We evaluate a novel method of rotator cuff repair that uses
      arthroscopic equipment to inject bone cement into placed suture anchors. A
      cadaver model was used to assess the pullout strength of this technique versus
      anchors without augmentation. METHODS: Six fresh-frozen matched pairs of upper
      extremities were screened to exclude those with prior operative procedures,
      fractures, or neoplasms. One side from each pair was randomized to undergo
      standard anchor fixation with the contralateral side to undergo anchor fixation
      augmented with bone cement. After anchor fixation, specimens were mounted on a
      servohydraulic testing system and suture anchors were pulled at 90 degrees  to
      the insertion to simulate the anatomic pull of the rotator cuff. Sutures were
      pulled at 1 mm/s until failure. FINDINGS: The mean pullout strength was 540 N
      (95% confidence interval, 389 to 690 N) for augmented anchors and 202 N (95%
      confidence interval, 100 to 305 N) for standard anchors. The difference in
      pullout strength was statistically significant (P < 0.05). INTERPRETATION: This
      study shows superior pullout strength of a novel augmented rotator cuff anchor
      technique. The described technique, which is achieved by extruding
      polymethylmethacrylate cement through a cannulated in situ suture anchor with
      fenestrations, significantly increased the ultimate failure load in cadaveric
      human humeri. This novel augmented fixation technique was simple and can be
      implemented with existing instrumentation. In osteoporotic bone, it may
      substantially reduce the rate of anchor failure.

PMID- 29587145
TI  - Spatial-Temporal Lineage Restrictions of Embryonic p63+ Progenitors Establish
      Distinct Stem Cell Pools in Adult Airways.
AB  - Basal cells (BCs) are p63-expressing multipotent progenitors of skin,
      tracheoesophageal and urinary tracts. p63 is abundant in developing airways;
      however, it remains largely unclear how embryonic p63+ cells contribute to the
      developing and postnatal respiratory tract epithelium, and ultimately how they
      relate to adult BCs. Using lineage-tracing and functional approaches in vivo, we
      show that p63+ cells arising from the lung primordium are initially multipotent
      progenitors of airway and alveolar lineages but later become restricted
      proximally to generate the tracheal adult stem cell pool. In intrapulmonary
      airways, these cells are maintained immature to adulthood in bronchi,
      establishing a rare p63+Krt5- progenitor cell population that responds to H1N1
      virus-induced severe injury. Intriguingly, this pool includes a CC10 lineage
      labeled p63+Krt5- cell subpopulation required for a full H1N1-response. These
      data elucidate key aspects in the establishment of regionally distinct adult stem
      cell pools in the respiratory system, potentially with relevance to other organs.

PMID- 29587147
TI  - Load transfer and periprosthetic fractures after total hip arthoplasty:
      Comparison of periprosthetic fractures of femora implanted with cementless distal
      load or proximal-load femoral components and measurement of the femoral strain at
      the time of implantation.
AB  - BACKGROUND: Little is known about the causes and mechanisms underlying
      periprosthetic fractures around femoral components particularly in relation to
      the stem design. In an in vitro study 20 pairs of fresh cadaveric femora were
      loaded to fracture axially and transversally. FINDINGS: When proximal femoral
      strain was measured at the time of impaction of cementless stems the load
      transfer was determined by the underlying anatomy rather than by the shape of the
      stem, so that the so-called "load transfer" properties - proximal or distal -
      ascribed to stem designs are a myth. The axial-load and the transverse-load model
      were then exposed to loads to failure (fracture) and showed a biphasic pattern
      throughout independent of the impact direction. In the second phase, the fracture
      phase proper, the bone behaved like a brittle solid. Failure occurred very
      rapidly within less than 5 milliseconds. The forces to failure were between 2 and
      11 kN. Most of the fractures (82.5%) occurred above the stem tip. INTERPRETATION:
      Note that the study was confined to early preosteointegration fractures. Neither
      the stem design nor the impact direction, i.e. on the knee or on the side of the
      hip, was related to the fracture morphology.

PMID- 29587148
TI  - Posterior or anterolateral approach in hip joint arthroplasty - Impact on frontal
      plane moment.
AB  - BACKGROUND: Anterolateral surgical approach in hip joint arthroplasty
      necessitates division of the hip abductor muscle complex, which may compromise
      postoperative gait observed in the frontal plane. The aim of the study was to
      compare frontal plane moment after hip joint arthroplasty by anterolateral or
      posterior approach and to explore which compensatory strategies patients use to
      decrease frontal plane moment. METHODS: Twenty-eight patients were randomized by
      sealed envelopes to hip resurfacing arthroplasty surgery by anterolateral (ad
      modum Watson) or posterior (ad modum Moore) approach, performed by two senior
      surgeons. Gait analyses were performed using 3D motion capture before surgery, 3,
      and 12 months after surgery. Peak ground reaction force was extracted for early
      and late stance and the corresponding frontal plane moment was defined. Measures
      of lateral trunk inclination, pelvic drop and hip abduction were obtained for the
      stance phase of the affected leg. FINDINGS: An effect of surgical approach on
      frontal plane moment for the affected leg was found during early stance phase (p
      = 0.006) where average frontal plane moment in the anterolateral groups was
      202.42 N mm/kg in less compared to the posterior group after one year. A similar
      effect from baseline to 12 months for trunk inclination (p = 0.03) and an overall
      negative correlation between frontal plane moment and trunk inclination was found
      (r = -0.66, p = 0.03). INTERPRETATION: Frontal plane moment during early stance
      was less one year after hip joint arthroplasty through anterolateral compared to
      posterior approach. Patients' primary strategy to reduce frontal plane moment
      seems to be increased lateral trunk inclination.

PMID- 29587150
TI  - Micro finite element analysis of dental implants under different loading
      conditions.
AB  - Osseointegration is paramount for the longevity of dental implants and is
      significantly influenced by biomechanical stimuli. The aim of the present study
      was to assess the micro-strain and displacement induced by loaded dental implants
      at different stages of osseointegration using finite element analysis (FEA).
      Computational models of two mandible segments with different trabecular densities
      were constructed using microCT data. Three different implant loading directions
      and two osseointegration stages were considered in the stress-strain analysis of
      the bone-implant assembly. The bony segments were analyzed using two approaches.
      The first approach was based on Mechanostat strain intervals and the second
      approach was based on tensile/compression yield strains. The results of this
      study revealed that bone surrounding dental implants is critically strained in
      cases when only a partial osseointegration is present and when an implant is
      loaded by buccolingual forces. In such cases, implants also encounter high
      stresses. Displacements of partially-osseointegrated implant are significantly
      larger than those of fully-osseointegrated implants. It can be concluded that the
      partial osseointegration is a potential risk in terms of implant longevity.

PMID- 29587149
TI  - Neurophysiological and cognitive effects of Transcranial Direct Current
      Stimulation in three girls with Rett Syndrome with chronic language impairments.
AB  - BACKGROUND: this study was based on both neurophysiological decelerated activity
      and communication deficits in Rett Syndrome (RTT). AIMS: the aim was to examine
      the neurophysiological and cognitive effects of Transcranial Direct Current
      Stimulation (tDCS) in three girls with RTT with chronic language impairments.
      METHODS AND PROCEDURES: we proposed an integrated intervention: tDCS and
      cognitive empowerment applied to language in order to enhance speech production
      (new functional sounds and new words). Because maximal gains usually are achieved
      when tDCS is coupled with behavioral training, we applied tDCS stimulation on
      Broca's area together with linguistic training. OUTCOMES AND RESULTS: the results
      indicated a general enhancement in language abilities (an increase in the number
      of vowel/consonant sounds and words and the production and comprehension through
      discrimination), motor coordination (functional movements), and
      neurophysiological parameters (an increase in the frequency and power of alpha,
      beta and theta bands). CONCLUSION AND IMPLICATIONS: we assume that tDCS
      stimulation combined with the cognitive empowerment applied to language can
      significantly influence a chronic impairment even in genetic syndromes. Our
      results provide data that support the role of tDCS in fostering brain plasticity
      and in particular in empowering speech production and comprehension in girls with
      RTT.

PMID- 29587151
TI  - Effect of preconditioning on silver leaching and bromide removal properties of
      silver-impregnated activated carbon (SIAC).
AB  - Silver impregnated activated carbon (SIAC) has been found to be effective in
      mitigating the formation of brominated-disinfection by products during drinking
      water treatment. However, there are still uncertainties regarding its silver
      leaching properties, and strategies for the prevention of silver leaching have
      remained elusive. This study focused on the evaluation of one type of
      commercially available SIAC for its ability to remove bromide while minimising
      silver leaching from the material. Both synthetic and real water matrices were
      tested. Depending on solution pH, it was found that changing the surface charge
      properties of SIAC, as measured by the point of zero charge pH, can result in
      additional bromide removal while minimising the extent of silver leaching. To
      better understand the mechanism of silver leaching from the SIAC, eight
      preconditioning environments, i.e. variable pH and ionic strength were tested for
      a fixed amount of SIAC and two preconditioning environments were selected for a
      more detailed investigation. Experiments carried out in synthetic water showed
      that preconditioning at pH 10.4 did not deteriorate the capacity of SIAC to
      remove bromide, but significantly decreased the release of silver in the form of
      ionic silver (Ag+), silver bromide (AgBr) and silver chloride (AgCl) from 40% for
      the pristine to 3% for the treated SIAC. This was confirmed using a groundwater
      sample. These results suggest that preconditioned SIAC has the potential to be an
      effective method for bromide removal with minimised silver leaching in a long
      term field application for drinking water production.

PMID- 29587152
TI  - Identifying, counting, and characterizing superfine activated-carbon particles
      remaining after coagulation, sedimentation, and sand filtration.
AB  - Superfine powdered activated carbon (SPAC; particle diameter ~1 MUm) has greater
      adsorptivity for organic molecules than conventionally sized powdered activated
      carbon (PAC). Although SPAC is currently used in the pretreatment to membrane
      filtration at drinking water purification plants, it is not used in conventional
      water treatment consisting of coagulation-flocculation, sedimentation, and rapid
      sand filtration (CSF), because it is unclear whether CSF can adequately remove
      SPAC from the water. In this study, we therefore investigated the residual SPAC
      particles in water after CSF treatment. First, we developed a method to detect
      and quantify trace concentration of carbon particles in the sand filtrate. This
      method consisted of 1) sampling particles with a membrane filter and then 2)
      using image analysis software to manipulate a photomicrograph of the filter so
      that black spots with a diameter >0.2 MUm (considered to be carbon particles)
      could be visualized. Use of this method revealed that CSF removed a very high
      percentage of SPAC: approximately 5-log in terms of particle number
      concentrations and approximately 6-log in terms of particle volume
      concentrations. When waters containing 7.5-mg/L SPAC and 30-mg/L PAC,
      concentrations that achieved the same adsorption performance, were treated, the
      removal rate of SPAC was somewhat superior to that of PAC, and the residual
      particle number concentrations for SPAC and PAC were at the same low level (100
      200 particles/mL). Together, these results suggest that SPAC can be used in place
      of PAC in CSF treatment without compromising the quality of the filtered water in
      terms of particulate matter contamination. However, it should be noted that the
      activated carbon particles after sand filtration were smaller in terms of
      particle size and were charge-neutralized to a lesser extent than the activated
      carbon particles before sand filtration. Therefore, the tendency of small
      particles to escape in the filtrate would appear to be related to the fact that
      their small size leads to a low destabilization rate during the coagulation
      process and a low collision rate during the flocculation and filtration
      processes.

PMID- 29587153
TI  - Two-dimensional 1H and 1H-detected NMR study of a heterogeneous biocatalyst using
      fast MAS at high magnetic fields.
AB  - Nuclear magnetic resonance (NMR) is a powerful tool for investigating atomic
      scale structure in heterogeneous or composite materials where long-range order is
      absent. In this work solid-state 1H and 1H-detected NMR experiments were
      performed with fast magic angle spinning (nuR = 75 kHz) and at high magnetic
      fields (B0 = 20 T) and used to gain structural insight into a heterogeneous
      biocatalyst consisting of an enzyme, human carbonic anhydrase II (hCA II),
      covalently immobilized on epoxy-functionalized silica. Two-dimensional 1H-1H
      NOESY-type correlation experiments were able to provide information on 1H
      environments in silica, epoxy-silica and the immobilized enzyme. Two distinct
      signals originating from water protons were observed: water associated with the
      surface of the silica and the water associated with the immobilized enzyme.
      Additional two-dimensional 1H-1H double-single quantum (DQ-SQ) correlation
      experiments suggested that the immobilized enzyme is not in close contact with
      the silica surface. Most significantly, comparison of two-dimensional 1H-15N
      spectra of the immobilized enzyme and the solution-state enzyme confirmed that
      the structural integrity of the protein is well preserved upon covalent
      immobilization.

PMID- 29587154
TI  - Intracellular osteopontin negatively regulates toll-like receptor 4-mediated
      inflammatory response via regulating GSK3beta and 4EBP1 phosphorylation.
AB  - Toll-like receptors (TLRs) play an important role in host defense against
      invading pathogens. By initiating a signal transduction cascade, TLRs lead to the
      release of pro-inflammatory cytokines. However, the inappropriate activation of
      TLR signaling could result in inflammatory disorders or autoimmune diseases.
      Osteopontin (OPN) has been reported to be an inflammatory cytokine participating
      in cell-mediated immunity. However, the role of OPN in TLR-mediated immune
      responses is poorly understood. In the present study, OPN-deficient (OPN-/-)
      macrophages exhibited significantly higher levels of pro-inflammatory cytokines
      after stimulation with lipopolysaccharide (LPS). Our study also demonstrated that
      the intracellular OPN (iOPN) isoform acted as a negative regulator to inhibit LPS
      induced inflammatory responses. Compared to WT macrophages, OPN-/- macrophages
      had lower Akt phosphorylation levels and higher GSK3beta phosphorylation levels,
      which were downregulated by p-Akt. Moreover, as a down-stream target of Akt,
      4EBP1 was hypo-phosphorylated in OPN-/- macrophages compared to 4EBP1 in WT
      macrophages. These findings reveal that iOPN can regulate GSK3beta and 4EBP1
      phosphorylation to inhibit TLR4-mediated inflammatory responses.

PMID- 29587155
TI  - CXCL8 hyper-signaling in the aortic abdominal aneurysm.
AB  - There are indications for elevated CXCL8 levels in abdominal aortic aneurysm
      disease (AAA). CXCL8 is concurrently involved in neutrophil-mediated inflammation
      and angiogenesis, two prominent and distinctive characteristics of AAA. As such
      we considered an evaluation of a role for CXCL8 in AAA progression relevant.
      ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in
      AAA wall samples. A role for CXCL8 in AAA disease was tested through the oral
      CXCR1/2 antagonist DF2156A in the elastase model of AAA disease. There is an
      extreme disparity in aortic wall CXCL8 content between AAA and aortic
      atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261]
      (AAA) vs. 23 [2.8-89] (atherosclerotic aorta) ug/g protein (P < 1 . 10-14)), and
      abundant expression of the CXCR1 and 2 receptors in AAA. Array analysis followed
      by pathway analysis showed that CXCL8 hyper-expression in AAA is followed
      increased by IL-8 signaling (Z-score for AAA vs. atherosclerotic control: 2.97, p
      < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated AAA
      formation and prevented matrix degradation in the murine elastase model of AAA
      disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of
      AAA, interference with the pathway constitutes a promising target for medical
      stabilization of AAA.

PMID- 29587156
TI  - Morphometric analysis of posterior fossa and craniovertebral junction in subtypes
      of Chiari malformation.
AB  - OBJECTIVES: Chiari malformations (CMs) are a group of disorders defined by
      anatomic anomalies of the cerebellum, brainstem, and craniovertebral junction
      (CVJ). In this study, we aimed to investigate morphometry of posterior fossa and
      CVJ in subtypes of CM and in control group, and to bring up a matter a
      correlation with demographic data and subtypes of CM. PATIENTS AND METHODS: The
      study group included patients managed for CM between 2012 and 2016 and control
      group. Radiological evaluation was studied by special programs and formulas.
      Intracranial volumes and morphometric datas of posterior fossa and CVJ were
      recorded retrospectively. RESULTS: Of the 141 patients, 91 had CM and 50 were
      control group participants. Mean age was 34.75. Patients were classified as CM-0
      (n:10), CM-1 (n:45), CM-1.5 (n:21), CM-2 (n:15). There were statistically
      significance between Chiari subtypes by syringomyelia (SM) presence (p ? 0.01),
      SM localization (p ? 0.01), posterior fossa volume (PFV) (p ? 0.01), length of
      clivus (LoC) and length of subocciput (LoSO) (p ? 0.01 for both), angle between
      clivus and subocciput (C-SO angle) (p ? 0.01), and clivo-dental angle (C-D angle)
      (p ? 0.01). CONCLUSION: On morphometric comparison of CM subtypes we concluded
      that etiological differences lead to morphological differences. CM-2 has
      remarkable differences from both other subtypes and the control group.

PMID- 29587157
TI  - Cancer mortality rates and spillover effects among different areas: A case study
      in Campania (southern Italy).
AB  - The present study analyses the spatial distribution of cancer mortality rates in
      Campania (an Italian region with the highest population density), in which
      residents in several areas are exposed to major environmental health hazards. The
      paper has the methodological aims of verifying the existence, or otherwise, of a
      spatial correlation between mortality from different types of cancer and the
      occurrence of some specific area characteristics, using both Bayesian statistics
      and spatial econometrics. We show that the use of the Spatial Empirical Bayes
      Smoothed Rate, instead of the more commonly used Raw Rate, allows a more
      comprehensive analysis of the mortality rate, highlighting the existence of
      different cluster sizes throughout the region, according to the type of cancer
      mortality rate analysed. By using a Spatial Durbin model we verify that cancer
      mortality rates are related to the environmental characteristics of specific
      areas with spatial spillover effects. Our results validate the hypothesis that
      living along the coast by Mt Vesuvius and, to a lesser extent, along the Domitio
      Flegreo coast NW of Naples and in more urbanised municipalities, increases the
      risk of dying of cancer. By contrast, living in less urbanised municipalities,
      with the presence of natural and historical attractions, has a positive effect on
      the residents' health, reducing their risk of disease. In both cases significant
      spillover effects (negative and positive) are found in municipalities close to
      the areas in question. Despite a number of reasonable limitations, our findings
      may provide useful information support for policy makers to foster knowledge,
      awareness and informed participation of citizens.

PMID- 29587158
TI  - Low-Frequency rTMS as an alternative for suicidality and depression, in a patient
      with multiple medical comorbidities precluding ECT.

PMID- 29587159
TI  - A cluster randomized controlled platform trial comparing group MEmory specificity
      training (MEST) to group psychoeducation and supportive counselling (PSC) in the
      treatment of recurrent depression.
AB  - Impaired ability to recall specific autobiographical memories is characteristic
      of depression, which when reversed, may have therapeutic benefits. This cluster
      randomized controlled pilot trial investigated efficacy and aspects of
      acceptability, and feasibility of MEmory Specificity Training (MEST) relative to
      Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N
      = 62). A key aim of this study was to determine a range of effect size estimates
      to inform a later phase trial. Assessments were completed at baseline, post
      treatment and 3-month follow-up. The cognitive process outcome was memory
      specificity. The primary clinical outcome was symptoms on the Beck Depression
      Inventory-II at 3-month follow-up. The MEST group demonstrated greater
      improvement in memory specificity relative to PSC at post-intervention (d = 0.88)
      and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in
      depressive symptoms at 3-month follow-up (d = 0.67). However, there was no
      support for a greater improvement in depressive symptoms at 3 months following
      MEST relative to PSC (d = -0.04). Although MEST generated changes on memory
      specificity and improved depressive symptoms, results provide no indication that
      MEST is superior to PSC in the resolution of self-reported depressive symptoms.
      Implications for later-phase definitive trials of MEST are discussed.

PMID- 29587160
TI  - Extending neutron autoradiography technique for boron concentration measurements
      in hard tissues.
AB  - The neutron autoradiography technique using polycarbonate nuclear track detectors
      (NTD) has been extended to quantify the boron concentration in hard tissues, an
      application of special interest in Boron Neutron Capture Therapy (BNCT). Chemical
      and mechanical processing methods to prepare thin tissue sections as required by
      this technique have been explored. Four different decalcification methods
      governed by slow and fast kinetics were tested in boron-loaded bones. Due to the
      significant loss of the boron content, this technique was discarded. On the
      contrary, mechanical manipulation to obtain bone powder and tissue sections of
      tens of microns thick proved reproducible and suitable, ensuring a proper
      conservation of the boron content in the samples. A calibration curve that
      relates the 10B concentration of a bone sample and the track density in a Lexan
      NTD is presented. Bone powder embedded in boric acid solution with known boron
      concentrations between 0 and 100 ppm was used as a standard material. The
      samples, contained in slim Lexan cases, were exposed to a neutron fluence of 1012
      cm-2 at the thermal column central facility of the RA-3 reactor (Argentina). The
      revealed tracks in the NTD were counted with an image processing software. The
      effect of track overlapping was studied and corresponding corrections were
      implemented in the presented calibration curve. Stochastic simulations of the
      track densities produced by the products of the 10B thermal neutron capture
      reaction for different boron concentrations in bone were performed and compared
      with the experimental results. The remarkable agreement between the two curves
      suggested the suitability of the obtained experimental calibration curve. This
      neutron autoradiography technique was finally applied to determine the boron
      concentration in pulverized and compact bone samples coming from a sheep
      experimental model. The obtained results for both type of samples agreed with
      boron measurements carried out by ICP-OES within experimental uncertainties. The
      fact that the histological structure of bone sections remains preserved allows
      for future boron microdistribution analysis.

PMID- 29587161
TI  - A hybrid method on sourceless sensitivity calculation for airborne gamma-ray
      spectrometer.
AB  - The sensitivity calculation of airborne gamma-ray spectrometer (AGS) is usually
      performed by on-ground or in-flight calibration. However, both methods are cost
      ineffective or not permissive, especially for artificial radioisotopes with short
      half-lives. Alternative to these methods is the Monte Carlo simulation, which has
      been widely applied over the last few decades. The greatest challenge to the
      practicability of the Monte Carlo simulation in the AGS calibration is its low
      computational efficiency for ensuring an acceptable reliability. This article
      proposes a hybrid numerical method for the sourceless AGS calibration by
      combining the deterministic point-kernel approach and the Monte Carlo simulation.
      This method is not only more efficient than the source-based calibration by an
      empirical method, but also independent of the source availability for on-ground
      or in-flight calibration. For a given soil test model, AGS sensitivities
      calculated by this hybrid method agree well with those obtained from the
      empirical method for the in-flight calibration.

PMID- 29587162
TI  - QA measurement of gamma-ray dose and neutron activation using TLD-400 for BNCT
      beam.
AB  - TLD-400 (CaF2:Mn) chips were applied for the gamma-ray dose measurement in a PMMA
      phantom exposed to a BNCT beam because of their very low neutron sensitivity.
      Since TLD-400 chips possess an adequate amount of Mn activator they have been
      employed in this work simultaneously for neuron activation measurement. The self
      irradiation TL signals owing to the decay of the neutron induced 56Mn activity
      have been applied for a calibration of the TLD-400 chip in situ, where the
      activities were measured by an HPGe detector system and the energy deposition per
      disintegration of 56Mn was calculated by applying a Monte Carlo code. It was
      accidentally found that the irradiated TLD-400 chips were capable of emitting
      prominent scintillation lights owing to the induced 56Mn activity, which can
      easily be recorded by the TLD reader without heating and after a calibration can
      be used to determine the 56Mn activity.

PMID- 29587163
TI  - Insights on limits of detection, precision and accuracy in TXRF analysis of trace
      and major elements in environmental solid suspensions.
AB  - In this work, the analytical capability of the total reflection X-ray
      fluorescence technique with the S2 PICOFOX spectrometer was investigated. A set
      of certified reference materials was prepared as solid particulate for TXRF
      analysis. Experimental data of sensitivity, limits of detection and recovery for
      many elements were obtained. Good sensitivity and limits of detection with a good
      recovery range of around 90-110% were achieved. Thus, the TXRF technique exhibits
      a good analytical potential for its applicability on different materials.

PMID- 29587164
TI  - Nitric oxide donors for peripheral artery disease.
AB  - Current management of peripheral arterial disease involves risk factor
      modification and revascularisation, but many patients are still left with
      debilitating symptoms. Therefore, new treatment strategies are needed. The
      importance of nitric oxide, and its role in regulating endothelial function, is
      well-established. Altering the nitric oxide pathway has been extensively studied
      as a means of treating vascular disease, including peripheral arterial disease.
      Statins and ACE inhibitors have been shown to enhance endogenous nitric oxide and
      improve intermittent claudication symptoms. Studies using l-arginine have
      produced differing results, for reasons for yet fully understood. A greater
      understanding of the nitric oxide pathway, and its enzymatic control, has
      generated more potential therapeutic targets to alter NO levels.

PMID- 29587165
TI  - Disrupted functional connectivity patterns of the insula subregions in drug-free
      major depressive disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is characterized by impairments in
      emotional and cognitive functions. Emerging studies have shown that cognition and
      emotion interact by reaching identical brain regions, and the insula is one such
      region with functional and structural heterogeneity. Although previous
      literatures have shown the role of insula in MDD,it remains unclear whether the
      insular subregions show differential change patterns in MDD. METHODS: Using the
      resting-state fMRI data in a group of 23 drug-free MDD patients and 34 healthy
      controls (HCs), we investigated whether the abnormal connectivity patterns of
      insular sub-regions or any behavioural correlates can be detected in MDD. Further
      hierarchical cluster analysis was used to identify the functional connectivity
      clustering patterns of insular sub-regions. RESULTS: Compared with HCs, the MDD
      exhibited higher connectivities between dorsal agranular insula and inferior
      parietal lobule and between ventral dysgranular and granular insula and
      thalamus/habehula, and lower connectivity of hypergranular insula to subgenual
      anterior cingulate cortex. Moreover, the three subregions with significant group
      differences were in three separate functional systems along anterior-to-posteior
      gradient. The anterior and middle insula showed positive correlation with
      depressive severity, while the posterior insular was to the contrary.
      LIMITATIONS: The small and unbalanced sample size, only included moderate and
      severe depression and the possible inter-individual differences may limit the
      interpretability. CONCLUSIONS: These findings provided evidences for the MDD
      related effects in functional connectivity patterns of insular subregions, and
      revealed that the subregions might be involved in different neural circuits
      associated with the contrary impacts on the depressive symptoms.

PMID- 29587166
TI  - Difference in proinflammatory cytokines produced by monocytes between patients
      with major depressive disorder and healthy controls.
AB  - BACKGROUND: Immune activation and suppression in patients with major depressive
      disorders (MDD) have been both reported in different studies. We assume that
      these findings may indicate innate immunological tolerance in MDD, with
      subclinical elevated level of proinflammatory cytokines and the decrease in
      innate immune response while encountering pathogens. METHODS: Peripheral
      monocytes of 50 untreated patients with MDD and 40 healthy controls were isolated
      and cultured, with or without 10 ng/ml lipopolysacchride (LPS) for 6 h (6 h,
      LPS+/-), and with LPS for 18 h (18, LPS+). The cell culture supernatants were
      collected to measure concentrations of tumor necrosis factor-alpha (TNF-alpha),
      interleukin 6 (IL-6), and interleukin 1 beta (IL-1beta). RESULTS: The baseline
      concentrations of IL-6 and IL-1beta (6 h, LPS-) were significantly higher in the
      MDD group than those in the control group. There was no significant difference of
      TNF-alpha between the two groups. The fold changes of LPS-induced secretion of IL
      6 and TNF-alpha from monocytes cultured for 6 and 18 h were all lower in the
      patient groups, and that was true for IL-1beta as monocytes cultured for 18 h.
      LIMITATIONS: Given the gap between the results of in vitro experiments and the
      actual response that happens in vivo when the immune system encounters pathogens
      from the external world, future research should include in vivo methods to test
      the results of the current study. CONCLUSIONS: Patients with MDD may have
      subclinical inflammation during a depressive episode, and the reduced response to
      LPS in monocytes indicates innate immunological tolerance.

PMID- 29587168
TI  - Integrating DNA damage repair with the cell cycle.
AB  - DNA is labile and constantly subject to damage. In addition to external mutagens,
      DNA is continuously damaged by the aqueous environment, cellular metabolites and
      is prone to strand breakage during replication. Cell duplication is orchestrated
      by the cell division cycle and specific DNA structures are processed differently
      depending on where in the cell cycle they are detected. This is often because a
      specific structure is physiological in one context, for example during DNA
      replication, while indicating a potentially pathological event in another, such
      as interphase or mitosis. Thus, contextualising the biochemical entity with
      respect to cell cycle progression provides information necessary to appropriately
      regulate DNA processing activities. We review the links between DNA repair and
      cell cycle context, drawing together recent advances.

PMID- 29587167
TI  - Effects of silicon nanoparticles on molecular, chemical, structural and
      ultrastructural characteristics of oat (Avena sativa L.).
AB  - Nowadays, nanoparticles are extensively being utilized in medicine, industry, and
      agriculture thus distributed into the environment. Hence, it is essential to
      examine exactly the impact of these materials on a variety of organisms,
      including various species of plants. Therefore, in the current study, we compared
      the effects of sodium silicate and nano silicon (SiNP) (both at two
      concentrations of 5 and 10 mM) separately on lignification of the xylem cell
      wall, antioxidant enzyme activities, ultrastructure of leaf and root cells,
      expression of silicon transporter (Lsi1) and phenylalanine ammonia lyase (PAL),
      and also evaluated the protein content and chemical content of oat plants (Avena
      sativa L.) cultured hydroponically. The results indicated that SiNPs didn't have
      a toxic effect on the oat plants, and in many cases they enhanced plant growth.
      The effect of SiNPs on the chemical content of the treated plants was almost
      identical with silicate. The silicon transporter (Lsi1) gene was expressed in
      plants exposed to SiNPs, however, at lower levels (~37% in roots) than those
      exposed to silicate treatments. The SiNPs increased PAL expression and
      lignification in leaves and roots, however, at lower levels those of silicate
      (?50% in fourth leaves of 10 mM concentration). They were aggregated in the roots
      (268-366 nm) and deposited in nano size on the cell walls of leaves. In general,
      their effects in the plants were identical to silicate but differed in intensity.

PMID- 29587169
TI  - Attachment within life history theory: an evolutionary perspective on individual
      differences in attachment.
AB  - In this article, we discuss theory and research on how individual differences in
      adult attachment mediate the adaptive calibration of reproductive strategies,
      cognitive schemas, and emotional expression and regulation. We first present an
      integration of attachment theory and life history theory. Then, we discuss how
      early harsh and/or unpredictable environments may promote insecure attachment by
      hampering parents' ability to provide sensitive and reliable care to their
      children. Finally, we discuss how, in the context of harsh and/or unpredictable
      environments, different types of insecure attachment (i.e. anxiety and avoidance)
      may promote evolutionary adaptive reproductive strategies, cognitive schemas, and
      emotional expression and regulation profiles.

PMID- 29587170
TI  - The continuous vs discontinuous use of restorative safety behaviors on symptoms
      of contamination fear: An experimental investigation.
AB  - BACKGROUND AND OBJECTIVES: Cognitive-behavioral theorists posit that safety
      behaviors (SBs) interfere with important exposure processes and should be removed
      from therapy. However, there is growing evidence to suggest that restorative SBs
      (RSB; those that allow for full confrontation with a core threat) do not
      adversely affect exposure outcomes, and their implementation during exposure
      should be further examined. METHODS: The current study evaluated exposure with
      the continuous use of RSB (E + CONT) versus discontinuation of RSB (E + DISC), in
      comparison to exposure with no RSB (ERP). Sixty-seven nonclinical participants
      completed 15 trials of exposure in which they touched a potentially contaminated
      stimulus with or without RSB. Behavioral approach tasks were completed at
      pretreatment, post-treatment, and two-week follow-up to examine changes in
      subjective distress and degree of behavioral approach. RESULTS: The three
      conditions were not different on clinical symptoms and behavioral approach at
      post-treatment and follow-up, indicating that the hypothesized superiority effect
      of E + DISC was not supported. However, ratings obtained during repeated exposure
      trials indicated that E + DISC evidenced greater symptom reduction following the
      removal of RSB. LIMITATIONS: The use of a healthy undergraduate sample and
      standardization of the exposure procedure. CONCLUSIONS: Although findings were
      contrary to hypotheses, these data provide added support for the benign role of
      RSB as compared to conventional exposure. Furthermore, the removal of RSB may
      lead to more favorable process outcomes during exposure. The theoretical and
      clinical implications of these findings are discussed, and future directions are
      provided.

PMID- 29587171
TI  - Impact of carpal tunnel syndrome on ulnar nerve at wrist: Systematic review.
AB  - Considerable debate exists in the literature about possible anomalies of ulnar
      nerve at wrist in carpal tunnel syndrome (CTS). We systematically reviewed the
      literature about electrophysiologic and morphologic changes of ulnar nerve at
      wrist in CTS. We carried out a comprehensive search using PubMed from 1963
      through October 2017. Data were extracted and the quality of the included studies
      was evaluated. Twenty-eight studies were selected. Seventy-nine percent of the
      studies report abnormalities of the ulnar nerve conduction. There was a relation
      between the median and ulnar nerve conduction in almost all the papers, i.e.,
      conduction impairment of the ulnar nerve increased with increasing severity of
      median nerve involvement, emerging as a process correlated with damage of the
      median nerve. Seventy-five percent of ultrasonographic studies report changes of
      ulnar nerve cross sectional area in CTS. Morphologic and functional changes of
      the ulnar nerve and/or Guyon canal are reported by 100% of papers addressed to
      this topic. Several papers quoted in this review have some flaws. The key message
      of present review is that electrophysiological and morphological changes of the
      ulnar nerve at the wrist can occur in CTS, although the possibility of an
      overestimation of the phenomenon needs to be considered.

PMID- 29587173
TI  - Trends in female and male drunken driving prevalence over thirty years:
      Triangulating diverse sources of evidence (1985-2015).
AB  - INTRODUCTION: Women have lower rates of drunken driving than men, but their share
      of arrests has been climbing since 1985. These trends may stem from changes in
      women's lives that lead to more drinking and driving, or to greater reductions in
      male drinking and driving. Alternatively, changes in policy and enforcement that
      focus on less intoxicated offenders may inadvertently target female-typical
      offending patterns. This paper tracked male and female drunken driving rates and
      the DUI sex ratio in the United States from 1985 to 2015 across three data
      sources. METHODS: The sex ratio and prevalence estimates were derived from
      official arrest statistics from Uniform Crime Reports, self-reports from the
      Centers for Disease Control and Prevention, and traffic fatality data from the
      National Highway and Transportation Safety Administration. Rates were assessed
      for four age groups (18-20, 21-34, 35-49, and 50-64), and drunken driving trends
      tested using Augmented Dickey-Fuller time-series methods. RESULTS: Decreases in
      DUI rates stagnated over the first decade of 2000, but have again begun to
      decline, according to self-reports and traffic fatality data, for all sex-by-age
      groups. Still, the gender gap in DUI arrests continues to narrow. From 1990 to
      the early 2000s, changes in social control that made female DUI more visible
      narrowed the gender gap in arrests. In more recent years, narrowing of the gap is
      due primarily to male rates declining more steeply than female rates. CONCLUSION:
      Results indicate that we need more research to understand why female declines
      have not kept pace with male declines and perhaps more targeted prevention
      efforts aimed at women.

PMID- 29587172
TI  - Client and clinician-rated characteristics of problem gamblers with and without
      history of gambling-related illegal behaviors.
AB  - Individuals with gambling disorder are at an elevated risk for engaging in
      gambling-related illegal behaviors. The present study examined client (N = 88)
      and clinician ratings (N = 30) of client characteristics associated with a
      history of gambling-related illegal behaviors. We also examined client
      characteristics associated with history of arrest for a gambling-related crime.
      Gambling-related illegal behaviors and arrest were common (57.3% and 23.9%,
      respectively) in the present sample. Clients of younger age, and those with
      greater gambling-related financial consequences, lifetime alcohol problems,
      impulsivity, mood symptoms, and daily living role difficulties were more likely
      to report gambling-related illegal behaviors. Clients who had been arrested for a
      gambling-related crime were more likely to report daily living and role
      functioning difficulties and lifetime alcohol problems. Clinicians rated clients
      with a history of gambling-related illegal behaviors and/or gambling-related
      arrests as more impulsive, and clinicians also endorsed higher rates of treatment
      failure among these clients. Both client and clinician report suggested that
      clients with a history of illegal behaviors may have a variety of comorbid
      problems that may be a focus of clinical intervention.

PMID- 29587174
TI  - Translation and validation study of the Chinese version Iconographical Falls
      Efficacy Scale-Short Version (Icon-FES).
AB  - BACKGROUND: The 30-item Iconographical Falls Efficacy Scale (Icon-FES) is the
      first instrument developed to assess older people's concern about falling using
      pictures. The short version of Icon-FES (10-item Icon-FES) was translated and
      adapted to a local Chinese version, and its psychometric properties was evaluated
      in Chinese older people. METHODS: A forward-backward translation procedure was
      used, followed by an expert panel review to finalize the 10-item Chinese Icon
      FES. One hundred and sixteen Hong Kong Chinese older people (65-95 years) were
      assessed using the 10-item Chinese Icon-FES in conjunction with the Chinese
      version 7-item Falls Efficacy Scale-International (FES-I (Ch)). RESULTS: Five of
      the 10 items in the Icon-FES were modified to achieve the conceptual and cultural
      relevance in local context. The final Chinese Icon-FES had excellent internal
      consistency (Cronbach's alpha = 0.91) and test-retest reliability (intra-class
      correlation coefficient ICC = 0.93). High correlation was found between the
      Chinese Icon-FES and FES-I (Ch) (r = .75, p < .001). Construct validity was
      supported by its ability to discriminate between groups related to demographic
      and fall risk factors. CONCLUSIONS: The Chinese Icon-FES is a valid, efficient
      and easy-to-use instrument for understanding of local Chinese older people's
      concerns about falling in Hong Kong.

PMID- 29587175
TI  - Prescription of potentially inappropriate medications to older adults. A
      nationwide survey at dispensing pharmacies in Japan.
AB  - OBJECTIVES: Prescriptions to older adults were surveyed to elucidate factors
      associated with potentially inappropriate medications (PIMs) in Japan. METHODS:
      Adults aged >=65 years, who were prescribed medications at 585 dispensing
      pharmacies across Japan, participated (N = 180,673). Data were collected between
      October 1 and October 31, 2014. RESULTS: Proportion of polypharmacy and that of
      PIMs increased with age (p < 0.001). Analgesic drugs were most commonly
      prescribed for the older adults aged 65-74 years, whereas benzodiazepines were
      prescribed most commonly for those aged over 75 years. A logistic regression
      analysis revealed that the increase of PIMs was explained by polypharmacy and
      mainly the use of central nervous systems (CNS) and psychotropic drugs.
      CONCLUSIONS: The increased prevalence of polypharmacy with age and the common use
      of CNS and psychotropic medications account for the PIMs in old age in the
      current nationwide survey.

PMID- 29587177
TI  - Advances in functional genetic screening with transposons and CRISPR/Cas9 to
      illuminate cancer biology.
AB  - Large-scale genome sequencing studies have identified a wealth of mutations in
      human tumors and have dramatically advanced the field of cancer genetics.
      However, the functional consequences of an altered gene in tumor progression
      cannot always be inferred from mutation status alone. This underscores the
      critical need for complementary methods to assign functional significance to
      mutated genes in cancer. Transposons are mobile genetic elements that serve as
      powerful tools for insertional mutagenesis. Over the last decade, investigators
      have employed mouse models with on-demand transposon-mediated mutagenesis to
      perform unbiased genetic screens to identify clinically relevant genes that
      participate in the pathogenesis of human cancer. Two distinct DNA transposon
      mutagenesis systems, Sleeping Beauty (SB) and PiggyBac (PB), have been applied
      extensively in vivo and more recently, in ex vivo settings. These studies have
      informed our understanding of the genes and pathways that drive cancer
      initiation, progression, and metastasis. This review highlights the latest
      progress on cancer gene identification for specific cancer subtypes, as well as
      new technological advances and incorporation of the CRISPR/Cas9 toolbox into
      transposon-mediated functional genetic studies.

PMID- 29587176
TI  - Close encounters of the RNAi kind: the silencing life of the adherens junctions.
AB  - The adherens junction has been historically considered an essential structural
      component of epithelial tissues. Although primarily discussed as targets of
      signaling pathways responsible for cell fate and tissue remodeling, they have
      also emerged as critical signaling regulators in developmental processes or in
      disease progression. The recent discovery of a functional localized RNA
      interference (RNAi) machinery at epithelial adherens junctions revealed a new
      layer of signaling regulation that is directly associated with the structure
      itself. This and other findings also indicate that our view of the subcellular
      localization of RNAi requires revisiting. A number of questions emerge regarding
      the physiological role and the modes of regulation of the junctional RNAi
      machinery, pointing towards new directions of investigation.

PMID- 29587178
TI  - Functional network integration and attention skills in young children.
AB  - Children acquire attention skills rapidly during early childhood as their brains
      undergo vast neural development. Attention is well studied in the adult brain,
      yet due to the challenges associated with scanning young children, investigations
      in early childhood are sparse. Here, we examined the relationship between age,
      attention and functional connectivity (FC) during passive viewing in multiple
      intrinsic connectivity networks (ICNs) in 60 typically developing girls between 4
      and 7 years whose sustained, selective and executive attention skills were
      assessed. Visual, auditory, sensorimotor, default mode (DMN), dorsal attention
      (DAN), ventral attention (VAN), salience, and frontoparietal ICNs were identified
      via Independent Component Analysis and subjected to a dual regression. Individual
      spatial maps were regressed against age and attention skills, controlling for
      age. All ICNs except the VAN showed regions of increasing FC with age. Attention
      skills were associated with FC in distinct networks after controlling for age:
      selective attention positively related to FC in the DAN; sustained attention
      positively related to FC in visual and auditory ICNs; and executive attention
      positively related to FC in the DMN and visual ICN. These findings suggest
      distributed network integration across this age range and highlight how multiple
      ICNs contribute to attention skills in early childhood.

PMID- 29587179
TI  - Molecular characterization, antibiotic resistance pattern and biofilm formation
      of Vibrio parahaemolyticus and V. cholerae isolated from crustaceans and humans.
AB  - Human infection with pathogenic vibrios is associated with contaminated seafood
      consumption. In the present study, we examined 225 crustaceans collected from
      retail markets in Egypt. Stool samples from gastroenteritis patients were also
      examined. Bacteriological and molecular examinations revealed 34 (15.1%) V.
      parahaemolyticus and 2 (0.9%) V. cholerae from crustaceans, while V.
      parahaemolyticus isolates were identified in 3 (3%) of the human samples. The
      virulence-associated genes tdh and/or trh were detected in 5.9% and 100% of the
      crustacean and human samples, respectively, whereas the two V. cholerae isolates
      were positive for the ctx and hlyA genes. Antibiotic sensitivity revealed high
      resistance of the isolates to the used antibiotics and an average MAR index of
      0.77. Biofilm formation at different temperatures indicated significantly higher
      biofilm formation at 37  degrees C and 25  degrees C compared with 4  degrees C.
      Frequent monitoring of seafood for Vibrio species and their antibiotic, molecular
      and biofilm characteristics is essential to improve seafood safety.

PMID- 29587180
TI  - Prioritization of potential drug targets against P. aeruginosa by core proteomic
      analysis using computational subtractive genomics and Protein-Protein interaction
      network.
AB  - Pseudomonas aeruginosa is an opportunistic gram-negative bacterium that has the
      capability to acquire resistance under hostile conditions and become a threat
      worldwide. It is involved in nosocomial infections. In the current study,
      potential novel drug targets against P. aeruginosa have been identified using
      core proteomic analysis and Protein-Protein Interactions (PPIs) studies. The non
      redundant reference proteome of 68 strains having complete genome and latest
      assembly version of P. aeruginosa were downloaded from ftp NCBI RefSeq server in
      October 2016. The standalone CD-HIT tool was used to cluster ortholog proteins
      (having >=80% amino acid identity) present in all strains. The pan-proteome was
      clustered in 12,380 Clusters of Orthologous Proteins (COPs). By using in-house
      shell scripts, 3252 common COPs were extracted out and designated as clusters of
      core proteome. The core proteome of PAO1 strain was selected by fetching PAO1's
      proteome from common COPs. As a result, 1212 proteins were shortlisted that are
      non-homologous to the human but essential for the survival of the pathogen. Among
      these 1212 proteins, 321 proteins are conserved hypothetical proteins.
      Considering their potential as drug target, those 321 hypothetical proteins were
      selected and their probable functions were characterized. Based on the
      druggability criteria, 18 proteins were shortlisted. The interacting partners
      were identified by investigating the PPIs network using STRING v10 database.
      Subsequently, 8 proteins were shortlisted as 'hub proteins' and proposed as
      potential novel drug targets against P. aeruginosa. The study is interesting for
      the scientific community working to identify novel drug targets against MDR
      pathogens particularly P. aeruginosa.

PMID- 29587181
TI  - The "Social-mobile autopsy": The evolution of psychological autopsy with new
      technologies in forensic investigations on suicide.
AB  - Suicide is a huge deal in general public health, representing the second cause of
      mortality in young people worldwide. The suicidal setting analysis is usually
      performed through psychological autopsy, a method of investigation commonly used
      to study what leads to suicide. Psychological autopsy, though, requires the
      involvement of family and friends, or the finding of a diary or a suicide note.
      Nowadays, this is not always possible, especially during adolescence, the more if
      we consider new categories of people that are more used to live in a web
      dimension, than in a real one. So, with the advent of a new kind of social system
      including the web, psychological autopsy, as we know it, is not enough to
      determine the setting of an event. We here report the case of a 17-year old girl
      who committed suicide by hanging down from her house, leaving no suicide note. We
      propose a new investigation method developed through the analysis of phone
      messages and Facebook profile in order to better reconstruct the event. Although
      the standing difficulties in reconsidering the intimate motivations leading to
      such a decision, psychological autopsy nowadays needs to consider also social
      networks in order to prevent similar situations and even reconstruct the
      psychological dimension of the fact. We propose a model of Social-mobile autopsy.

PMID- 29587182
TI  - The role of domain-general cognitive resources in children's construction of a
      vitalist theory of biology.
AB  - Some episodes of learning are easier than others. Preschoolers can learn certain
      facts, such as "my grandmother gave me this purse," only after one or two
      exposures (easy to learn; fast mapping), but they require several years to learn
      that plants are alive or that the sun is not alive (hard to learn). One
      difference between the two kinds of knowledge acquisition is that hard cases
      often require conceptual construction, such as the construction of the biological
      concept alive, whereas easy cases merely involve forming new beliefs formulated
      over concepts the child already has (belief revision, a form of knowledge
      enrichment). We asked whether different domain-general cognitive resources
      support these two types of knowledge acquisition (conceptual construction and
      knowledge enrichment that supports fast mapping) by testing 82 6-year-olds in a
      pre-training/training/post-training study. We measured children's improvement in
      an episode involving theory construction (the beginning steps of acquisition of
      the framework theory of vitalist biology, which requires conceptual change) and
      in an episode involving knowledge enrichment alone (acquisition of little known
      facts about animals, such as the location of crickets' ears and the color of
      octopus blood). In addition, we measured children's executive functions and
      receptive vocabulary to directly compare the resources drawn upon in the two
      episodes of learning. We replicated and extended previous findings highlighting
      the differences between conceptual construction and knowledge enrichment, and we
      found that Executive Functions predict improvement on the Vitalism battery but
      not on the Fun Facts battery and that Receptive Vocabulary predicts improvement
      the Fun Facts battery but not on the Vitalism battery. This double dissociation
      provides new evidence for the distinction between the two types of knowledge
      acquisition, and bears on the nature of the learning mechanisms involved in each.

PMID- 29587183
TI  - Dynamic cognitive models of intertemporal choice.
AB  - Traditionally, descriptive accounts of intertemporal choice have relied on static
      and deterministic models that assume alternative-wise processing of the options.
      Recent research, by contrast, has highlighted the dynamic and probabilistic
      nature of intertemporal choice and provided support for attribute-wise
      processing. Currently, dynamic models of intertemporal choice-which account for
      both the resulting choice and the time course over which the construction of a
      choice develops-rely exclusively on the framework of evidence accumulation. In
      this article, we develop and rigorously compare several candidate schemes for
      dynamic models of intertemporal choice. Specifically, we consider an existing
      dynamic modeling scheme based on decision field theory and develop two novel
      modeling schemes-one assuming lexicographic, noncompensatory processing, and the
      other built on the classical concepts of random utility in economics and
      discrimination thresholds in psychophysics. We show that all three modeling
      schemes can accommodate key behavioral regularities in intertemporal choice. When
      empirical choice and response time data were fit simultaneously, the models built
      on random utility and discrimination thresholds performed best. The results also
      indicated substantial individual differences in the dynamics underlying
      intertemporal choice. Finally, model recovery analyses demonstrated the benefits
      of including both choice and response time data for more accurate model selection
      on the individual level. The present work shows how the classical concept of
      random utility can be extended to incorporate response dynamics in intertemporal
      choice. Moreover, the results suggest that this approach offers a successful
      alternative to the dominating evidence accumulation approach when modeling the
      dynamics of decision making.

PMID- 29587184
TI  - Recruitment and retention strategies for an urban adolescent study: Lessons
      learned from a multi-center study of community-based asthma self-management
      intervention for adolescents.
AB  - Intervention studies with urban adolescents and families affected by asthma are
      critical to improving the disproportionate morbidity in this population.
      Community-based recruitment and retention strategies in a multi-site longitudinal
      project evaluating an asthma self-management intervention for adolescents are
      presented. Successful recruitment strategies depended on the geographic and
      cultural characteristics of each study site. Partnering with providers and groups
      known to the target population and in-person contact with target population were
      found effective. Flexibility accommodating modified and new approaches, securing
      multiple contacts and repeating mailings as well as capitalizing on the benefits
      of subject payment was critical to achieving long-term subject engagement of 85%
      in the study. Ongoing monitoring and adjustment of recruitment and retention
      strategies is recommended.

PMID- 29587185
TI  - Pregnancy outcomes among women with epilepsy: A retrospective cohort study.
AB  - OBJECTIVE: The objective of this study was to compare adverse pregnancy outcomes
      between pregnancies that involve epilepsy and those that do not and are
      identified as normal for the purposes of this paper. METHODS: A retrospective
      cohort study was carried out by accessing the maternal-fetal medicine (MFM)
      database to identify and review records of singleton pregnancies with epilepsy
      but with no other underlying disease (study group). A parallel group of low-risk
      pregnancies was randomly allocated as the control group. The adverse outcomes
      between the two groups were compared. The primary outcomes included rates of
      spontaneous abortion, small for gestational age (SGA), preterm birth (PTB), low
      birth weight (LBW), and preeclampsia. RESULTS: From a total of 44,708 deliveries,
      148 pregnancies involving mothers with epilepsy and a control group of 1480
      normal pregnancies were compared. The rates of spontaneous abortion, PTB, LBW,
      and cesarean section were slightly but significantly higher in the study group
      with a relative risk of 6.6 (95% confidence interval (CI): 1.9-23.3), 1.6 (95%
      CI: 1.1-2.2), 1.6 (95% CI: 1.1-2.3), and 1.5 (95% CI: 1.1-2.1), respectively,
      whereas other adverse outcomes were comparable. In the subgroup analysis, adverse
      outcomes tended to be higher in women with active epilepsy. However, only the
      rates of SGA in the group in which the disorder is active and PTB in the presence
      of seizures within 6months of conception were significantly increased.
      CONCLUSIONS: Pregnancies with epilepsy, even in cases with multidisciplinary care
      and no other risk factors, are still significantly associated with higher adverse
      outcomes.

PMID- 29587186
TI  - Role of beta2/3-specific GABA-A receptor isoforms in the development of
      hippocampus kindling epileptogenesis.
AB  - OBJECTIVE: Subunit-specific positive allosteric modulators (PAMs) of gamma
      aminobutyric acid-A (GABA-A) receptors are commonly used to uncover the role of
      GABA-A receptor isoforms in brain function. Recently, we have designed novel PAMs
      selective for beta2/3-subunit containing GABA-A receptors (beta2/3-selective
      PAMs) that are nonbenzodiazepine site-mediated and do not show an alpha-subunit
      isoform selectivity, yet exhibit anxiolytic efficacy with reduced potential for
      sedation, cognitive impairment, and tolerance. In this study, we used three novel
      beta2/3-selective PAMs (2-261, 2-262, and 10029) with differential beta2/3
      subunit potency to identify the role of beta2/3-selective receptor isoforms in
      limbic epileptogenesis. METHODS: Experimental epileptogenesis was induced in mice
      by daily hippocampus stimulations until each mouse showed generalized (stage 5)
      seizures. Patch-clamp electrophysiology was used to record GABA-gated currents.
      Brain levels of beta2/3-selective PAMs were determined for mechanistic
      correlations. RESULTS: Treatment with the beta2/3-selective PAMs 2-261 (30mg/kg),
      2-262 (10mg/kg), and 10029 (30mg/kg), 30min prior to stimulations, significantly
      suppressed the rate of development of kindled seizure activity without affecting
      the afterdischarge (AD) signal, indicating their disease-modifying activity. The
      beta2/3-selective agents suppressed chemical epileptogenesis in the
      pentylenetetrazol model. Test doses of these agents were devoid of acute
      antiseizure activity in the kindling model. CONCLUSION: These findings
      demonstrate that beta2/3-selective PAMs can moderately retard experimental
      epileptogenesis, indicating the protective role of beta2/3-subunit GABA-A
      receptor isoforms in the development of epilepsy.

PMID- 29587187
TI  - Characteristics and healthcare situation of adult patients with tuberous
      sclerosis complex in German epilepsy centers.
AB  - OBJECTIVE: The objective of the present study was to collect systematic data on
      the care of adult patients with tuberous sclerosis complex (TSC) in German
      epilepsy centers, to describe the characteristics of patients in this age group,
      and to clarify whether and how the recommended interdisciplinary care is
      implemented. METHODS: This retrospective survey involved 12 major epilepsy
      centers in Germany. Aggregated data were collected based on an electronic
      questionnaire that addressed the sociodemographic data, characteristics of the
      epilepsy syndromes, and general healthcare setting of adult patients with TSC.
      RESULTS: The survey included 262 patients (mean age: 36.2+/-9.0years) with TSC,
      most of whom were reported to live in either a home for persons with a disability
      (37.0%), a residential care home (6.9%), or with their parents (31.1%). A further
      13.0% were self-sustaining, and 8.8% were living with a partner. Most patients
      presented with focal (49.6%) or multifocal (33.2%) epilepsy, with complex
      partial, dialeptic, and automotor seizures in 66% of patients and generalized
      tonic-clonic seizures in 63%. Drug-refractory epilepsy was seen in 78.2% of
      patients, and 17.6% were seizure-free at the time of the survey. Of the 262
      patients, presurgical diagnostics were performed in 27% and epilepsy surgery in
      9%, which rendered 50% of these patients seizure-free. Renal screening had been
      performed in 56.1% within the last three years and was scheduled to be performed
      in 58.0%. Cases of renal angiomyolipoma were present in 46.9% of the patients.
      Dermatologic and pulmonary screenings were known to be planned for only few
      patients. CONCLUSION: Despite TSC being a multisystem disorder causing
      considerable impairment, every fifth adult patient is self-sustaining or living
      with a partner. In clinical practice, uncontrolled epilepsy and renal
      angiomyolipoma are of major importance in adult patients with TSC. Most patients
      suffer from focal or multifocal epilepsy, but epilepsy surgery is performed in
      less than 10% of these patients. Interdisciplinary TSC centers may help to
      optimize the management of patients with TSC regardless of age and ensure early
      and adequate treatment that also considers the advances in new therapeutic
      options.

PMID- 29587188
TI  - Nonconvulsive status epilepticus after cessation of convulsive status epilepticus
      in pediatric intensive care unit patients.
AB  - Little is known about pediatric patients suffering from nonconvulsive status
      epilepticus (NCSE) after convulsive status epilepticus (CSE) cessation. The aim
      of this study was to identify in pediatric patients the clinical characteristics
      of NCSE after CSE cessation and the factors that contribute to patient outcomes.
      Data from clinical features, electroencephalography (EEG) characteristics,
      neuroimaging findings, treatments, and prognosis were systematically summarized,
      and the associations between clinical characteristics and prognosis were
      quantified. Thirty-eight children aged 51days-14years, 2months were identified in
      the Chongqing Medical University pediatric intensive care unit as having
      experienced NCSE after CSE cessation between October 1, 2014 and April 1, 2017.
      All patients were comatose, 15 of whom presented subtle motor signs. The most
      common underlying etiology was acute central nervous system (CNS) infection.
      Electroencephalography (EEG) data showed that, during the NCSE period, all
      patients had several discrete episodes (lasting from 30s to 6h long), and the
      most common duration was 1-5min. The ictal onset locations were classified as
      focal (16 patients, 42.1%), multiregional independent (10 patients, 26.3%), and
      generalized (12 patients, 31.6%). Wave morphologies varied during the ictal and
      interictal periods. Neuroimaging detected signal abnormalities in the cerebral
      cortex or subcortex of 33 patients with NCSE (87%), which were classified as
      either multifocal and consistent with extensive cortical edema (21 patients,
      55.3%) or focal (12 patients, 31.6%). Twelve patients were on continuous
      intravenous phenobarbital, and 31 were on continuous infusion of either midazolam
      (27 patients) or propofol (4 patients). At least one other antiepileptic drug was
      prescribed for 32 patients. Three patients were on mild hypothermia therapy. The
      duration of NCSE lasted <24h for 20 patients and >24h for 18 patients. The
      mortality rate was 21.1%, and half of the surviving patients had severe
      neurological morbidity. Our results indicated that EEG monitoring after treatment
      of CSE was essential to the recognition of persistent seizures. The clinical
      features, EEG characteristics, and neuroimaging findings varied during the NCSE
      period. The morbidity is high in pediatric patients who had NCSE after CSE.
      Convulsive status epilepticus (CSE) duration and neuroimaging results may be
      related to the prognosis.

PMID- 29587189
TI  - Synthesis of NiO nanoparticles via a green route using Monsonia burkeana: The
      physical and biological properties.
AB  - NiO nanoparticles have emerged as ideal candidates in various fields due to their
      magnetic, electrical and optical properties. The coupling of plant extracts that
      have anticancer and antibacterial properties with NiO nanoparticles has increased
      their usage in the biomedical field. In this work, we report on the novel
      synthesis of NiO nanoparticles using a local medicinal plant, Monsonia burkenea.
      The nickel nanoparticles were characterized using Fourier transform infrared
      spectroscopy (FTIR), Energy dispersive X-ray analysis (EDX), Scanning electron
      microscope (SEM), High-resolution transmission electron microscope (HRTEM) and X
      ray diffraction (XRD). FTIR showed that the extraction of the plant
      phytochemicals was successful and the green synthesized nanoparticles from plants
      contained the phytochemical groups that are found in the Monsonia burkeana plant.
      XRD and HRTEM confirmed the successful formation of NiO nanoparticles with an
      average particle size range of 20 nm. These results were also corroborated by
      elemental mapping and EDX, where the dominant groups were identified.The Monsonia
      burkeana NiO particles exhibited selective bactericidal activity against Gram
      negative strains, such as E. coli and P. aeruginosa. Additionally, cytotoxicity
      studies showed the materials did not have any anti proliferative effect against
      A549 lung cancer cells but could be used as potential drug delivery vehicles
      against human cancers.

PMID- 29587190
TI  - Reduction of soluble dipeptidyl peptidase 4 levels in plasma of patients infected
      with Middle East respiratory syndrome coronavirus.
AB  - Dipeptidyl peptidase 4 (DPP4) is a receptor for MERS-CoV. The soluble form of
      DPP4 (sDPP4) circulates systematically and can competitively inhibit MERS-CoV
      entry into host cells. Here, we measured the concentration of sDPP4 in the plasma
      and sputa of 14 MERS-CoV-infected patients of various degrees of disease
      severity. The concentration of sDPP4 in the plasma of MERS patients (474.76 +/-
      108.06 ng/ml) was significantly lower than those of healthy controls (703.42 +/-
      169.96 ng/ml), but there were no significant differences among the patient
      groups. Interestingly, plasma levels of IL-10 and EGF were negatively and
      positively correlated with sDPP4 concentrations, respectively. The sDPP4 levels
      in sputa were less than 300 ng/ml. Viral infection was inhibited by 50% in the
      presence of more than 8000 ng/ml of sDPP4. Therefore, sDPP4 levels in the plasma
      of MERS patients are significantly reduced below the threshold needed to exert an
      antiviral effect against MERS-CoV infection.

PMID- 29587191
TI  - An emerging and expanding clade accounts for the persistent outbreak of
      Coxsackievirus A6-associated hand, foot, and mouth disease in China since 2013.
AB  - Enterovirus (EV)-A71 and Coxsackievirus (CV)-A16 have historically been the major
      pathogens of hand, foot, and mouth disease (HMFD) in China; however, CV-A6, which
      had previously received little attention, became the predominant pathogen in
      2013, and has remained one of the common pathogens since then. In this work, we
      conducted a molecular epidemiology study of CV-A6-associated HFMD in Xiamen from
      2009 to 2015. The data showed CV-A6 pandemics had a certain periodicity rather
      than occurring randomly. Evolution analysis based on near-complete VP1 nucleotide
      sequences showed subgenotype D5 lineage 4 strains account for the persistent
      outbreak of CV-A6-associated HFMD in China since 2013. Alignment analysis
      revealed eight candidate amino acid substitutions in VP1, which may provide
      useful information for the research of CV-A6 virulence enhancement. This study
      contributed to elucidating the circulation patterns and genetic characteristics
      of CV-A6 in China; however, further surveillance and intervention in CV-A6
      epidemics is recommended.

PMID- 29587192
TI  - Hand-held optical sensor using denatured antibody coated electro-active polymer
      for ultra-trace detection of copper in blood serum and environmental samples.
AB  - An optimum copper concentration in environment is highly desired for all forms of
      life. We have developed an ultrasensitive copper sensor which functions from
      femto to micro molar concentration accurately (R2 = 0.98). The sensor is based on
      denatured antibody immunoglobulin G (IgG), immobilized on polyaniline (PAni)
      which in turn is the coating on the core of an optical fiber. The sensing relies
      on changes in evanescent wave absorbance in the presence of the analyte. The
      sensor showed excellent selectivity towards Cu (II) ions over all other metal
      ions. The sensor was tested with lake and marine water samples to determine
      unknown concentrations of copper ions and the recovery results were within 90
      115%, indicating reasonable accuracy. We further integrated the fiber-optic
      sensor with a miniaturized hand-held instrumentation platform to develop an
      accurate and field deployable device which can broadly be applicable to determine
      Cu (II) concentration in a wide range of systems - natural water bodies, soil as
      well as blood serum.

PMID- 29587193
TI  - Development of Cu nanoflowers modified the flexible needle-type microelectrode
      and its application in continuous monitoring glucose in vivo.
AB  - A minimally invasive glucose microbiosensor based the flexibly integrated
      electrode for continuous monitoring glucose in vivo has been developed in this
      study. This was achieved by coating needle-type microelectrode with Cu
      nanoflowers, nafion, glucose oxidase (GOD) and polyurethane (PU) membranes,
      successfully prepared with layer-by-layer deposition. The Cu nanomaterials
      provided a large specific surface area and electrocatalytic activity for glucose
      detection. The PU layers as mass-transport limiting membranes significantly
      enhanced the linearity and stability of sensors. The resulting biosensor
      exhibited a wide linear range of 0-20 mM, with a good sensitivity of 42.38 nA mM
      1 (correlation coefficient r2 was 0.99) and a fast response time of less than 15
      s. In vivo implantable experiments using anesthetized rats showed excellent real
      time response to the variation of blood glucose concentration. And the variation
      tendency of sensor output was consistent with that using the glucose meter.
      Overall, the results supported the suitability of this microsensor for measuring
      rapid changes of glucose in vivo. This work offers a promising approach in
      implantable device applications related to diabetes management as well as other
      medical diagnosis.

PMID- 29587194
TI  - Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with
      disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial
      peptide.
AB  - Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are
      receiving more and more attraction as drug delivery vehicles. Dry powder
      formulation that forms LCNPs upon hydration can be advantageous to make new
      routes of administration accessible. In this work, we investigate use of three
      disaccharides (lactose, trehalose and sucrose) as protective matrices for
      glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase
      behavior, particle size and size distributions at the different preparation steps
      were monitored by small angle x-ray scattering (SAXS) and dynamic light
      scattering (DLS). Particle appearance was imaged by cryogenic transmission
      electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial
      peptide AP114 (plectasin derivative) was incorporated in the formulations.
      Peptide encapsulation and release as well as in vitro antibacterial effect were
      investigated. Results showed that all freeze-dried powders did form particles
      with liquid crystalline structure upon hydration. However, a phase transition
      from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a
      consequence of sugar addition and the freeze-drying procedure. Data indicates
      that trehalose is the preferred choice of lyo-protectant in order to maintain a
      mono-modal particle size distribution. In addition, antimicrobial activity of
      AP114-containing formulations was found to be highest for the formulation
      containing trehalose. The release kinetics of AP114 from the nanoparticles was
      strongly affected by the dimensions of the hexagonal phase. Larger dimension of
      the hexagonal phase, significantly improved the release of AP114 and
      antimicrobial activity of the formulation.

PMID- 29587195
TI  - TiO2: Si nanotube/1T-MoSe2 nanosheet hybrids with highly efficient hydrogen
      evolution catalytic activity.
AB  - Transition metal dichalcogenides exhibit an excellent catalytic activity for
      hydrogen evolution reaction and continue to attract many studies. Some
      heterojunctions are also used to enhance the catalytic activity. In this work,
      the TiO2 nanotubes/MoSe2 and Si-doped TiO2 NTs/MoSe2 hybrids were synthesized.
      The MoSe2 in the hybrids exhibited nanosheet morphology and metallic (1T)
      structure with high conductivity and catalytic activity for hydrogen evolution
      reaction. Moreover, MoSe2 decoration provided high light absorbance for the
      hybrids and highly efficient interface-induced effect at the heterojunction.
      Furthermore, the Si-doping increased specific surface area and hydrophilicity.
      Thus, the Si-doped TiO2 NTs/MoSe2 hybrids showed remarkably greater
      photocatalytic and electrocatalytic activities than the nanotubes.

PMID- 29587196
TI  - Effect of diet and packaging system on the microbial status, pH, color and
      sensory traits of rabbit meat evaluated during chilled storage.
AB  - The combined effect of two dietary lipid sources (sunflower vs linseed oil) and
      three packaging methods (PVC film - BAG, modified atmosphere CO2 20% + 80% O2 -
      MAP, and vacuum - VAC) on the shelf-life (pH, color, microbial count, sensory
      traits) of rabbit loins was tested at days 1, 4 and 10 of refrigerated storage.
      Linseed oil did not adversely affect neither the physical or sensory traits, nor
      the microbiological quality of rabbit meat throughout the shelf-life trial. The
      three packaging methods were all similarly effective in maintaining the physical
      and sensory quality of the meat, irrespective of the different dietary lipid
      sources and thus different susceptibility to oxidation. MAP and VAC were more
      effective than BAG in preserving rabbit meat hygienic quality, as highlighted by
      the microbial count analyzed at day 4 of shelf-life (P < 0.001). At day 10, the
      microbiological quality didn't differ between MAP and VAC rabbit meat samples.

PMID- 29587197
TI  - A pilot study demonstrating the efficacy of transcutaneous bilirubin meters to
      quantitatively differentiate contusions from Congenital Dermal Melanocytosis.
AB  - OBJECTIVE: Congenital Dermal Melanocytosis (CDM) can be difficult to
      differentiate from contusions. The need for a prompt and accurate diagnosis is
      best illustrated in cases where child abuse and maltreatment is of concern.
      Transcutaneous bilirubin (TCB) spectrophotometry has been well established to
      measure bilirubin under the skin for jaundice in infants. The use of TCB
      spectrometry has not been used to identify or differentiate contusions from CDM.
      We hypothesized that bilirubin, a degradation product of hemoglobin, would be
      elevated in contusions but not in CDM thus demonstrating the efficacy of a novel
      diagnostic technique to compliment or improve on physical assessment alone.
      METHODS: Pilot study with thirty-seven infants and children noted to have CDM and
      fifty-six infants, children and adults with contusions underwent measurement of
      their lesion with TCB spectrometry. In each patient, the affected skin was
      scanned along with the adjacent unaffected native skin allowing an internal
      control for individual pigment variation. RESULTS: TCB measurements of CDM
      resulted in lower transcutaneous bilirubin values that were not significantly
      different from adjacent native skin pigmentation. This was in contrast to
      cutaneous contusions, which resulted in a higher measured value (mean 5.01 mg/dL)
      compared to adjacent native tissue (1.24 mg/dL) demonstrating a four-fold
      increase in measurement at the lesion site (P < 0.001). Direct comparison of a
      DeltaTCB value (lesion measurement minus the adjacent tissue) demonstrated a
      significantly higher value in contusions compared to CDM with a mean value of
      3.77 and 0.12 mg/dL, respectively (P < 0.001). CONCLUSIONS: TCB Spectrometry as a
      novel diagnostic technique has the potential to discern contusions from CDM and
      may therefore have the ability to compliment the use of physical assessment
      alone.

PMID- 29587198
TI  - Do emotion regulation difficulties explain the association between executive
      functions and child physical abuse risk?
AB  - This study examined the associations between executive functioning problems,
      emotion regulation difficulties, and risk for perpetrating child physical abuse
      (CPA). It was hypothesized that: (a) poor executive functions (i.e., working
      memory problems and inhibition/switching problems) would be associated with
      higher levels of emotion regulation difficulties and CPA risk; (b) emotion
      regulation difficulties would be positively associated with CPA risk; and (c)
      emotion regulation difficulties would partially explain the association between
      executive functions (i.e., working memory problems and inhibition/switching
      problems) and CPA risk. To examine these predictions, a sample of 133 general
      population parents (31% fathers) completed self-report measures of CPA risk,
      emotion regulation difficulties, working memory problems, and a performance-based
      measure of inhibition/switching skills. Results revealed that executive
      functioning problems were linked with emotion regulation difficulties, which in
      turn were associated with CPA risk. Moreover, emotion regulation difficulties
      explained the relationship between executive functions (working memory,
      inhibition/switching) and CPA risk. The final model accounted for 41% of the
      variance in CPA risk. Although additional research is needed, the present
      findings suggest that enhancing parents' executive functioning and teaching them
      effective emotion regulation skills may be important targets for CPA prevention
      efforts.

PMID- 29587199
TI  - Modeling the effects of parameter optimization on three bioretention tanks using
      the HYDRUS-1D model.
AB  - The operation effects of bioretention on different tanks were investigated
      through tests and simulations. Three layered bioretention tanks, namely, #1, #2,
      and #3, were selected for intermittent operation tests. The artificial filler
      layers of the tanks consisted of mixed fillers of fly ash and sand, blast furnace
      slag, and planting soil. Models were established by using HYDRUS-1D software
      based on test results. The sensitivity of model parameters was analyzed through
      Morris screening method. Results showed that return period, thickness of media
      layer, and solute concentration in the liquid phase were the parameters that
      significantly influenced the operation effects. The Nash-Sutcliffe efficiency
      coefficients of the models were greater than 0.85. The simulation results showed
      that the reduction effects at different inflow loads were better under low loads
      than under high loads. The comprehensive reduction rate of pollutant load was
      5.22% less under high concentrations than under low concentrations. The
      comprehensive reduction rates of water and pollutant loads were 35.97% and 20.68%
      greater, correspondingly, in the 1 year return period than in the 10 year return
      period. The artificial fillers comprising a mixture of fly ash and sand also
      showed the optimal reduction effects, with comprehensive reduction rates of
      69.33% and 83.08% for water and pollutant load, respectively. The reduction
      effects of water and pollutants for the #1 tank presented an upward trend,
      whereas those for the #2 tank showed a downward trend given an increase in
      planting soil thickness. An increase in media thickness enhanced the reduction
      effects. The media with 60 cm thickness demonstrated the optimal effect.

PMID- 29587200
TI  - Urban residents' response to and evaluation of low-carbon travel policies:
      Evidence from a survey of five eastern cities in China.
AB  - To address the problems of excessive energy consumption and global climate
      change, the Chinese government has issued numerous policies to guide urban
      residents' low-carbon travel behavior. To evaluate the validity of these policies
      from the perspective of public opinion, this study summarizes 22 policies from
      the four vantage points of economics, administration, technology, and public
      information and then measures residents' response to and evaluation of policies
      based on survey data on 1977 urban residents using stratified random sampling in
      five cities in eastern China. The results indicate that from the viewpoint of
      policy response, administrative policies for promoting public transport show the
      highest degree of response, followed by public information, technological, and
      economic policies. Specifically, the responses to parking and congestion fee
      policies are relatively stronger than those to vehicle purchase tax, vehicle and
      vessel tax, and fuel surcharge policies. Moreover, the responses to fuel
      surcharge policy are even weaker than car-restriction policies, including license
      plate number restriction, license-plate lottery, and license-plate auction
      policies. From the viewpoint of policy evaluation, administrative policies for
      promoting public transport obtain the highest evaluations, followed by economic
      and technological policies. Residents' evaluations of car-restriction and public
      information policies are the lowest. In addition, a four-paradigm model is
      introduced to illustrate residents' reactions to each policy in terms of response
      and evaluation. Finally, several implementation strategies, including the
      anterior, concurrent, optional, core, supporting, and assisting policy options
      are proposed to guide urban residents' low-carbon travel behavior.

PMID- 29587201
TI  - Recurrent Rapunzel syndrome - A rare tale of a hairy tail.
AB  - INTRODUCTION: Rapunzel syndrome is a rare condition predominantly found in
      trichophagic females that occurs when gastric trichobezoar extends beyond the
      pylorus and into duodenum, jejunum, ileum or even to colon. There are only five
      cases reported in literature. This case report has been reported in line with the
      SCARE criteria. PRESENTATION OF CASE: A 19 year old female, with a history of
      trichotillomania with trichophagia, who presented with epigastric pain and
      vomiting for 12 months. She underwent laparotomy ten years back to extract a
      trichobezoar, which was diagnosed to be Rapunzel syndrome and lack of follow-up
      resulted in recurrence. Further examination and imaging showed a large
      trichobezoar extending into small intestine. She underwent gastrotomy and
      entrerotomy and extraction of hairball. DISCUSSION: In a trichophagic female with
      abdominal pain, nausea and vomiting, and abdominal mass, diagnosis is done by
      ultrasound, CT scan and upper gastrointestinal endoscopy. Small trichobezoars can
      be removed endoscopically. Large (>20 cms)acutely symptomatic trichobezoars,
      especially when accompanied by Rapunzel syndrome, must be removed surgically by
      gastrotomy and enterotomy is required if impacted extension is present. Long-term
      surgical and psychiatric follow-up with psychotherapy and cognitive behavioural
      therapy along with selective serotonin reuptake inhibitors are critical to
      prevent recurrences. CONCLUSION: Although Rapunzel syndrome is an extremely rare
      disease, it should be considered when diagnosing young women, especially those
      with a history of trichophagia or trichotillomania. After the surgical removal of
      trichobezoars by laparotomy, long-term follow-up combined with psychiatric
      consultation is recommended to prevent recurrences.

PMID- 29587202
TI  - Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of
      STAT3 and NF-kappaB pathways.
AB  - Tofacitinib, a small molecule JAK inhibitor, has been widely used to reduce
      inflammation and inhibit progression of bone destruction in rheumatoid arthritis.
      STAT3, a downstream signaling molecule of JAK, plays a key role in the activation
      of signaling in response to inflammatory cytokines. Thus, targeting STAT3 may be
      an inspiring strategy for treating osteoclast-related diseases such as rheumatoid
      arthritis. In this study, we first investigated the effects of Stattic, a STAT3
      inhibitor, on receptor activator of NF-kappaB ligand (RANKL)-mediated
      osteoclastogenesis. Stattic inhibited osteoclast differentiation and bone
      resorption in RANKL-induced RAW264.7 cells in a dose-dependent manner. Stattic
      also suppressed RANKL-induced upregulation of osteoclast-related genes tartrate
      resistant acid phosphatase, matrix metalloproteinase 9, cathepsin K, RANK, tumor
      necrosis factor receptor-associated factor 6, and osteoclast-associated receptor
      in RAW264.7 cells. Moreover, Stattic exhibited an inhibitory effect on cell
      proliferation and cell cycle progression at higher dosages. At the molecular
      level, Stattic inhibited RANKL-induced activation of STAT3 and NF-kappaB
      pathways, without significantly affecting MAPK signaling. In addition, Stattic
      inhibited RANKL-induced expression of osteoclast-related transcription factors c
      Fos and NFATc1. Importantly, Stattic also prevented bone loss caused by
      ovariectomy. Together, our data confirm that Stattic restricts osteoclastogenesis
      and bone loss by disturbing RANKL-induced STAT3 and NF-kappaB signaling. Thus,
      Stattic represents a novel type of osteoclast inhibitor that could be useful for
      conditions such as osteoporosis and rheumatoid arthritis.

PMID- 29587203
TI  - Inhibitor of Bruton's tyrosine kinases, PCI-32765, decreases pro-inflammatory
      mediators' production in high glucose-induced macrophages.
AB  - Accumulating evidence has shown that macrophages play a vital role in development
      and pathogenesis of diabetic nephropathy (DN) by secreting inflammatory
      cytokines. Although Bruton's tyrosine kinases (Btk) is a biologically important
      molecule implicated in immune regulation, the role of Btk in high glucose (HG)
      stimulated inflammatory response in macrophages and the mechanism involved need
      further investigation. In our study, we used bone marrow-derived macrophages
      (BMMs) to investigate the involvement of Btk on HG-induced inflammatory cytokines
      expression and to explore the underlying mechanisms. We found that high glucose
      induced phosphorylation of Btk, MAPKs and NF-kappaB, and the expression of
      downstream inflammation cytokines monocyte chemo-attractant protein-1 (MCP-1),
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Btk
      inhibitor (PCI-32765) not only down-regulated ERK1/2 phosphorylation and NF
      kappaB activation, but also decreased the secretion of MCP-1, TNF-alpha and IL
      1beta in HG-treated BMMs. These results indicate that Btk plays an important role
      in HG-induced inflammatory cytokines expression and that PCI-32765 may be used as
      an immunoregulatory agent against hyperglycemia-induced inflammatory response in
      DN.

PMID- 29587204
TI  - Leukotriene D4 induces cellular senescence in osteoblasts.
AB  - Aging is associated with the development of osteoporosis, in which cellular
      senescence in osteoblasts plays a key role. Leukotriene D4 (LTD4), an important
      cysteinyl leukotriene (cysLT), is a powerful pro-inflammatory mediator formed
      from arachidonic acid. However, little information regarding the effects of LTD4
      on the pathogenesis of osteoporosis has been reported before. In the present
      study, we defined the physiological roles of LTD4 in cellular senescence in
      osteoblasts. Our results indicate that LTD4 treatment decreased the expression of
      SIRT1 in a dose-dependent manner in MC3T3-E1 osteoblastic cells. Additionally,
      LTD4 significantly increased the expression of p53, p21 and plasminogen activator
      inhibitor-1 (PAI-1). LTD4 was also found to elevate the activity of beta
      galactosidase (SA-beta-Gal) but to prevent BrdU incorporation. Our results
      indicate that cysteinyl leukotriene receptor 1 (cysLT1R) could be detected in
      MC3T3-E1 osteoblastic cells at both the mRNA and protein levels. However, cysLT2R
      was not expressed in these cells. Interestingly, we found that knockdown of
      cysLT1R or use of the selective cysLT1R antagonist montelukast abolished the LTD4
      induced reduction in SIRT1 and increase in p53, p21, and PAI-1. Notably,
      knockdown of cysLT1R by transfection with cysLT1R siRNA or treatment with
      montelukast attenuated the LTD4-induced increase in SA-beta-Gal activity. Our
      study shows for the first time that LTD4 has a significant impact on cellular
      senescence in osteoblasts.

PMID- 29587205
TI  - Affective impairments in binge drinking: Investigation through emotional facial
      expression decoding.
AB  - OBJECTIVE: Binge drinking, an excessive alcohol consumption pattern frequently
      observed in young people, is known to be associated with psychological and
      cerebral deficits. While cognitive dysfunctions have been widely investigated,
      emotional abilities have scarcely been explored. Such an exploration would
      however offer a more exhaustive understanding of the deficits associated with
      binge drinking, as well as of the possible transition towards alcohol-dependence.
      METHODS: 46 young adults (23 binge drinkers, 12 women; 23 control participants,
      12 women) were recruited among university students. They performed an emotional
      recognition task consisting of the visual decoding of six basic emotions (i.e.
      anger, contempt, disgust, fear, happiness, and sadness). Accuracy scores and
      detection thresholds were collected for each emotion. RESULTS: Binge drinkers
      showed lower performance than control participants for the decoding of all
      emotions and increased detection threshold, this later reflecting less ability to
      capture an emotion. Binge drinking is thus associated with a need for higher
      emotional intensity to perform correct detection. Moreover, these emotional
      difficulties appear specifically related to alcohol consumption. CONCLUSION:
      These findings reinforce previous experimental evidence of altered emotional
      processing among binge drinkers, and extend these results for various emotional
      contents. They support the hypothesis of a continuum between binge drinking and
      alcohol-dependence, in which massive emotional impairments have been documented.
      Indeed, these impairments could be involved in the onset and maintenance of
      excessive alcohol consumption, notably through the established relationship
      between emotional deficits and social distress.

PMID- 29587206
TI  - Thoracic paravertebral catheterization for more than one year: A report of
      mastodynia.

PMID- 29587207
TI  - Videolaryngoscopy could decrease claims associated with dental injury.

PMID- 29587208
TI  - Modulation of transcription of genes related to the hypothalamic-pituitary
      gonadal and the hypothalamic-pituitary-adrenal axes in zebrafish (Danio rerio)
      embryos/larvae by androstenedione.
AB  - This study aimed to determine the effects of Androstenodione (AED) on the
      transcriptional expression of genes involved in the hypothalamic-pituitary
      gonadal (HPG) and the hypothalamic-pituitary-adrenal (HPA) axes in the zebrafish
      embryos/larvae. Zebrafish embryos were exposed to 0, 4.0, 45.0, 487.0, and 980.0
      ng/L of AED from the day of fertilization to 144 h post fertilization (hpf),
      during which the transcriptional profiles of key genes related to the HPG and HPA
      axes were examined daily using quantitative real-time PCR. The AED exposure
      significantly up-regulated several receptor signaling pathways and the key genes
      involved in various steps of the steroidogenic pathways were also affected. In
      addition, the AED exposure could significantly modulate the transcriptional
      profiles of the other target genes related to hypothalamic and pituitary
      hormones. The findings of this study suggest that AED, at environmentally
      relevant concentrations, affects the adrenal endocrine systems and the
      reproduction of zebrafish by interrupting the HPG and HPA axes.

PMID- 29587209
TI  - The behaviours of nurses that increase student accountability for learning in
      clinical practice: An integrative review.
AB  - OBJECTIVE: To identify nurses' behaviours that promote student accountability for
      learning in clinical practice. BACKGROUND: Health care services are experiencing
      significant strain in meeting clinical education requirements of increasing
      numbers of nursing students enrolled in undergraduate nursing programs.
      Internationally, the transition to university based education for nurses has seen
      the emergence of issues for busy clinicians trying to manage increasing workloads
      with responsibility for student learning. An understanding of what types of
      supervisor behaviours promote student accountability for learning, may support
      clinicians to more effectively manage their dual roles of clinical care and
      student support. DESIGN: An integrative approach was adopted for this review.
      DATA SOURCES: A search of the Cumulative Index of Nursing and Allied Health
      Literature, Pubmed, Scopus and Embase was undertaken, limited to articles
      published between 2000 and March 2017. REVIEW METHODS: Whittemore and Knafls'
      (2005) framework for conducting integrative reviews was used to ensure a
      methodological and rigorous approach. RESULTS: Nine studies were considered.
      Behaviours emerged in relation to four themes including: belongingness associated
      with a genuine partnership; empowerment and increasing student self-efficacy;
      trust linked to increasing and staged independence; and balancing clinical and
      educational requirements. CONCLUSION: Behaviours of nurses significantly
      influence students' accountability for learning and accordingly, their ability to
      be adequately prepared for professional nursing practice. Understanding
      behaviours that impact on students' approach to clinical placement can guide
      nurses in their approach to facilitating student learning, in particular,
      behaviours that increase student responsibility and independence over the
      continuum of clinical education.

PMID- 29587210
TI  - Variation in mercury concentration in juvenile Magellanic penguins during their
      migration path along the Southwest Atlantic Ocean.
AB  - The vulnerability of seabirds related to their migratory dynamics is frequently
      linked to environmental problems along the migration path. In this context,
      Magellanic penguins (Sphenicus magellanicus) seem to be vulnerable to an
      extensive range of environmental disturbances during their northward migration
      along the Atlantic waters of South America, which include by catch, marine debris
      ingestion, overfishing and environmental contamination. In this study, we
      investigate mercury accumulation in muscle and hepatic tissues of juveniles
      penguins collected along the Brazilian coast during three migratory seasonal
      years (2006, 2008 and 2012) and three areas along a latitudinal gradient. We
      found significant differences in Hg levels across the years, with higher hepatic
      Hg levels found in tissues of penguins sampled in 2008. The higher Hg levels in
      samples of penguins from 2008 might be attributed to variations in body condition
      or Hg uptake, associated with the trophic imbalance linked to an extreme El Nino
      event during that year. Significant differences in Hg accumulation across the
      latitudinal areas were also observed. The penguins sampled at the farthest area
      from the breeding ground presented the higher levels of Hg and also the poorest
      body condition. Body condition and other traits may influence the levels of
      chemical pollutants and decrease the migratory success rate in the juvenile age
      phase, compromising population dynamics.

PMID- 29587211
TI  - Tracing perfluoroalkyl substances (PFASs) in soils along the urbanizing coastal
      area of Bohai and Yellow Seas, China.
AB  - With the shift of fluorine chemical industry from developed countries to China
      and increasing demand for fluorine chemical products, occurrence of
      perfluoroalkyl substances (PFASs) in production and application areas has
      attracted more attention. In this study, 153 soil samples were collected from 21
      cities along the urbanizing coastal area of the Bohai and Yellow Seas. PFASs in
      this area were relatively higher, compared with other study areas. The
      concentrations ranged from 2.76 to 64.0 ng g-1, and those in most sites were
      between 2.76 and 13.9 ng g-1, with a predominance of perfluorooctanoic acid
      (PFOA) and perfluorooctane sulfonate (PFOS). Among the 21 coastal cities,
      contaminations of PFASs in Zibo, Nantong and Binzhou were elevated, which was
      likely affected by local fluorine chemical plants, equipment manufacturing and
      chemical industry, respectively. The total emissions of PFOA and PFOS were
      similar, with amount of 4431 kg and 4335 kg, respectively. Atmospheric deposition
      was the largest source, accounting for 93.2% of total PFOA and 69.6% of PFOS,
      respectively. In addition, due to application of aqueous film-forming foams
      (AFFFs) and sulfluramid, disposal of sewage sludge and stacking of solid waste,
      emission of PFOA and PFOS to soil was 1617 kg, accounting for 9.29% of the whole
      China. In general, pollution in Jiangsu, Shandong and Tianjin was more serious
      than those in Liaoning and Hebei, which was consistent with industrialization
      level and size of industrial sectors emitting PFASs.

PMID- 29587212
TI  - First evaluation of the use of down feathers for monitoring persistent organic
      pollutants and organophosphate ester flame retardants: A pilot study using
      nestlings of the endangered cinereous vulture (Aegypius monachus).
AB  - Raptor feathers have been increasingly used to assess pollutants in
      ecotoxicological monitoring studies. However, the suitability of down feathers to
      detect pollutants has not yet been investigated. In this study, concentrations of
      persistent organic pollutants (POPs) and organophosphate ester flame retardants
      (OPEs) were assessed in down and juvenile contour feathers of Spanish cinereous
      vulture (Aegypius monachus) nestlings (circa 73 days old) and contaminant
      concentrations were compared between both types of feathers from the same
      individuals. Concentrations of polychlorinated biphenyls (PCBs: 1.30-6.16 ng g-1
      dw feather), polybrominated diphenyl ethers (PBDEs: 0.23-1.35 ng g-1 dw feather),
      p,p'-dichlorodiphenyldichloroethylene (pp-DDE: 0.09-6.10 ng g-1 dw feather) and
      tris (1-chloro-2-propyl) phosphate (TCiPP: 0.86-48.96 ng g-1 dw feather) were
      significantly higher in down than in contour feathers. In contrast, contour
      feathers showed higher levels of the more volatile POP, lindane (0.25-3.12 ng g-1
      dw feather). Concentrations of hexachlorobenzene (HCB) and OPEs (except TCiPP)
      were similar between the two types of feathers. By showing high accumulation of
      the most persistent POPs investigated, down feathers presented a contamination
      profile similar to that previously described in raptor eggs. As these feathers
      grow during the first days of a vulture chicks life, they probably reflect the
      contaminant burden of the chick due to maternal transfer to the egg. Overall, the
      present study provides the first indication that down feathers may be useful for
      biomonitoring studies. Further research is needed to confirm whether nestling
      down feathers reflect the concentrations in the egg.

PMID- 29587213
TI  - Stereoselective bioaccumulation of chiral PCB 91 in earthworm and its metabolomic
      and lipidomic responses.
AB  - Stereoselective bioaccumulation, elimination, metabolomic and lipidomic responses
      of earthworm Eisenia fetida exposed to chiral polychlorinated biphenyl (PCB) 91
      in an earthworm-soil system were investigated. Preferential bioaccumulation of (
      )-PCB 91 and elimination of (+)-PCB 91 were observed following 50 and 500
      MUg/kgdwt exposures. Enantiomer fraction (EF) values decreased over time during
      the uptake and elimination periods. Metabolomics and lipidomics techniques based
      on ultra-performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry (UPLC-QTOF-MS) revealed significant changes in 108 metabolites after
      earthworms exposure to (+)-, (-)-, and (+/-)-PCB 91, compared to control groups.
      Forty two of these metabolites were identified as amino acids, nucleosides, fatty
      acids, dicarboxylic acids, vitamins or others. Lysophospholipids including six
      lysophosphatidylcholines (LPC), six lysophosphatidylethanolamine (LPE), eight
      lysophosphatidylinositol (LPI) and five lysophosphatidylserine (LPS) were also
      differentially expressed between exposure and control groups. Alterations in the
      levels of metabolites and lipids indicated stereoselective effects of chiral PCB
      91 on earthworm amino acid, energy, and nucleotide metabolism, neurodevelopment
      and gene expression. Overall, the effects of (+)-PCB 91 were more pronounced than
      that of (-)- and (+/-)-PCB 91.

PMID- 29587215
TI  - Global review and analysis of erythromycin in the environment: Occurrence,
      bioaccumulation and antibiotic resistance hazards.
AB  - Environmental observations of antibiotics and other pharmaceuticals have received
      attention as indicators of an urbanizing global water cycle. When connections
      between environment and development of antibiotic resistance (ABR) are
      considered, it is increasingly important to understand the life cycle of
      antibiotics. Here we examined the global occurrence of erythromycin (ERY) in: 1.
      wastewater effluent, inland waters, drinking water, groundwater, and estuarine
      and coastal systems; 2. sewage sludge, biosolids and sediments; and 3. tissues of
      aquatic organisms. We then performed probabilistic environmental hazard
      assessments to identify probabilities of exceeding the predicted no-effect
      concentration (PNEC) of 1.0 MUg L-1 for promoting ABR, based on previous modeling
      of minimum inhibitory concentrations and minimal selective concentrations of ERY,
      and measured levels from different geographic regions. Marked differences were
      observed among geographic regions and matrices. For example, more information was
      available for water matrices (312 publications) than solids (97 publications).
      ERY has primarily been studied in Asia, North America and Europe with the
      majority of studies performed in China, USA, Spain and the United Kingdom. In
      surface waters 72.4% of the Asian studies have been performed in China, while
      85.4% of the observations from North America were from the USA; Spain represented
      41.9% of the European surface water studies. Remarkably, results from PEHAs
      indicated that the likelihood of exceeding the ERY PNEC for ABR in effluents was
      markedly high in Asia (33.3%) followed by Europe (20%) and North America (17.8%).
      Unfortunately, ERY occurrence data is comparatively limited in coastal and marine
      systems across large geographic regions including Southwest Asia, Eastern Europe,
      Africa, and Central and South America. Future studies are needed to understand
      risks of ERY and other antibiotics to human health and the environment,
      particularly in developing regions where waste management systems and treatment
      infrastructure are being implemented slower than access to and consumption of
      pharmaceuticals is occurring.

PMID- 29587214
TI  - Assessment of airborne polycyclic aromatic hydrocarbons in a megacity of South
      China: Spatiotemporal variability, indoor-outdoor interplay and potential human
      health risk.
AB  - Although a number of studies have assessed the occurrence of atmospheric
      polycyclic aromatic hydrocarbons (PAHs) in indoor environment, few studies have
      systemically examined the indoor-outdoor interplay of size-dependent particulate
      PAHs and potential health risk based on daily lifestyles. In the present study,
      size-dependent particle and gaseous samples were collected both indoors and
      outdoors within selected schools, offices and residences located in three
      districts of Guangzhou, China with different urbanization levels during the dry
      and wet weather seasons. Results from measurements of PAHs showed that higher
      total PAH concentrations occurred in residential areas than in other settings and
      in indoor than in outdoor environments. Compositional profiles and size
      distribution patterns of particle-bound PAHs were similar indoors and outdoors,
      predominated by 4-and 5-ring PAHs and the 0.56-1.0 MUm particle fraction.
      Statistical analyses indicated that outdoor sources may have contributed to 38
      99% and 62-100% of the variations for indoor particle-bound and gaseous PAH
      concentrations, respectively. Incremental life cancer risk (ILCR) from human
      exposure to indoor and outdoor PAHs based on different lifestyles followed the
      order of adults > children > adolescents > seniors. All average ILCR values for
      four age groups were below the lower limit of the Safe Acceptable Range (10-6).
      In addition, the ILCR value for adults (average: 7.2 * 10-7; 95% CI: 5.4 * 10-8
      2.5 * 10-6), estimated from outdoor air PAH levels with 24-h exposure time, was
      significantly higher than our assessment results (average: 5.9 * 10-7; 95% CI:
      6.3 * 10-8-1.9 * 10-6), suggesting the significance of assessing human inhalation
      exposure risks of indoor and outdoor PAHs in urban air based on daily lifestyles.

PMID- 29587216
TI  - Emission and health risk assessment of volatile organic compounds in various
      processes of a petroleum refinery in the Pearl River Delta, China.
AB  - The process-specific emission of volatile organic compounds (VOCs) from a
      petroleum refinery in the Pearl River Delta, China was monitored to assess the
      health risk from VOCs to workers of this refinery. Over 60 VOCs were detected in
      the air samples collected from various sites in the refining, basic chemical, and
      wastewater treatment areas of the refinery using gas chromatography-mass
      spectrometry/flame ionization detection. The health risks of VOCs to the refinery
      workers were assessed using US Environmental Protection Agency (US EPA) and
      American Conference of Governmental Industrial Hygienists (ACGIH) methods. Monte
      Carlo simulation and sensitivity analysis were implemented to assess the
      uncertainty of the health risk estimation. The emission results showed that C5-C6
      alkanes, including 2-methylpentane (17.6%), 2,3-dimethylbutane (15.4%) and 3
      methylpentane (7.7%), were the major VOCs in the refining area. p-Diethylbenzene
      (9.3%), 2-methylpentane (8.1%) and m-diethylbenzene (6.8%) were dominant in the
      basic chemical area, and 2-methylpentane (20.9%), 2,3-dimethylbutane (11.4%) and
      3-methylpentane (6.5%) were the most abundant in the wastewater treatment area.
      For the non-cancer risk estimated using the US EPA method, the total hazard ratio
      in the basic chemical area was the highest (3.1 * 103), owing to the highest
      level of total concentration of VOCs. For the cancer risk, the total cancer risks
      were very high, ranging from 2.93 * 10-3 (in the wastewater treatment area) to
      1.1 * 10-2 (in the basic chemical area), suggesting a definite risk. Using the
      ACGIH method, the total occupational exposure cancer risks of VOCs in the basic
      chemical area were the highest, being much higher than those of refining and
      wastewater treatment areas. Among the areas, the total occupational exposure
      risks in the basic chemical and refining areas were >1, which suggested a cancer
      threat to workers in these areas. Sensitivity analysis suggested that improving
      the accuracy of VOC concentrations themselves in future research would advance
      the health risk assessment.

PMID- 29587217
TI  - Evaluation of different methods for assessing bioavailability of DDT residues
      during soil remediation.
AB  - Compared to the total chemical concentration, bioavailability is a better
      measurement of risks of hydrophobic organic contaminants (HOCs) to biota in
      contaminated soil or sediment. Many different bioavailability estimation methods
      have been introduced to assess the effectiveness of remediation treatments.
      However, to date the different methods have rarely been evaluated against each
      other, leading to confusions in method selection. In this study, four different
      bioavailability estimation methods, including solid phase microextraction (SPME)
      and polyethylene passive sampling (PE) aiming to detect free chemical
      concentration (Cfree), and Tenax desorption and isotope dilution method (IDM)
      aiming to measure chemical accessibility, were used in parallel to estimate in
      bioavailability of DDT residues (DDXs) in a historically contaminated soil after
      addition of different black carbon sorbents. Bioaccumulation into earthworm
      (Eisenia fetida) was measured concurrently for verification. Activated carbon or
      biochar amendment at 0.2-2% decreased earthworm bioaccumulation of DDXs by 83.9
      99.4%, while multi-walled carbon nanotubes had a limited effect (4.3-20.7%).
      While all methods correctly predicted changes in DDX bioavailability after black
      carbon amendment, passive samplers offered more accurate predictions. Predicted
      levels of DDXs in earthworm lipid using the estimated bioavailability and
      empirical BCFs matched closely with the experimentally derived tissue
      concentrations. However, Tenax and IDM overestimated bioavailability when the
      available DDX levels were low. Our findings suggested that both passive samplers
      and bioaccessibility methods can be used in assessing remediation efficiency,
      presenting flexibility in method selection. While accessibility-oriented methods
      offer better sensitivity and shorter sampling time, passive samplers may be more
      advantageous because of their better performance and computability for in situ
      deployment.

PMID- 29587218
TI  - Culture and transplantation of spermatogonial stem cells.
AB  - The spermatogonial transplantation technique was developed by Dr. Ralph Brinster
      in 1994. Transplanted spermatogonial stem cells (SSCs) produce germ cell colonies
      after microinjection into the seminiferous tubules of infertile mice. This
      technique provided the first functional assay for SSCs. Although it became
      possible to produce transgenic animals using this transplantation technique in
      2001, the lack of SSC culture systems prevented efficient genetic manipulation.
      To overcome this problem, a long-term SSC culture technique was developed in
      2003. Cultured SSCs, designated as germline stem cells, allow drug selection of
      transfected SSCs, and knockout mice were produced in 2006. Using these
      techniques, it is now possible to address basic biological questions of SSC
      biology. They also open up new possibilities for male germline manipulation. In
      this review, we will briefly summarize our findings on SSCs and discuss
      unresolved issues that remain to be addressed.

PMID- 29587219
TI  - Specific-age group sex estimation of infants through geometric morphometrics
      analysis of pubis and ischium.
AB  - Sex determination of unknown individuals is one of the primary goals of Physical
      and Forensic Anthropology. The adult skeleton can be sexed using both
      morphological and metric traits on a large number of bones. The human pelvis is
      often used as an important element of adult sex determination. However, studies
      carried out about the pelvic bone in subadult individuals present several
      limitations due the absence of sexually dimorphic characteristics. In this study,
      we analyse the sexual dimorphism of the immature pubis and ischium bones,
      attending to their shape (Procrustes residuals) and size (centroid size), using
      an identified sample of subadult individuals composed of 58 individuals for the
      pubis and 83 for the ischium, aged between birth and 1year of life, from the
      Granada osteological collection of identified infants (Granada, Spain). Geometric
      morphometric methods and discriminant analysis were applied to this study. The
      results of intra- and inter-observer error showed good and excellent agreement in
      the location of coordinates of landmarks and semilandmarks, respectively.
      Principal component analysis performed on shape and size variables showed
      superposition of the two sexes, suggesting a low degree of sexual dimorphism.
      Canonical variable analysis did not show significant changes between the male and
      female shapes. As a consequence, discriminant analysis with leave-one-out cross
      validation provided low classification accuracy. The results suggested a low
      degree of sexual dimorphism supported by significant sexual dimorphism in the
      subadult sample and poor cross-validated classification accuracy. The inclusion
      of centroid size as a discriminant variable does not imply a significant
      improvement in the results of the analysis. The similarities found between the
      sexes prevent consideration of pubic and ischial morphology as a sex estimator in
      early stages of development. The authors suggest extending this study by
      analysing the different trajectories of shape and size in later ontogeny between
      males and females.

PMID- 29587220
TI  - The purinergic P2X7 ion channel receptor-a 'repair' receptor in bone.
AB  - A strong skeleton relies on adaptation to varying physical demands and on
      maintenance of the bone tissue in order to avoid accumulation of micro-damage. In
      bone, the purinergic P2X7 ion channel receptor is expressed on both cells of the
      stromal lineage such as the bone forming osteoblasts and the mechano-sensing
      osteocytes and on cells belonging to the immune-related monocyte-macrophage
      lineage, the bone resorbing osteoclasts. Recent studies have demonstrated that
      the receptor plays important roles in the anabolic responses to mechanical
      loading on bone and, together with the pannexin1 hemi-channel, in the process of
      initiating bone remodeling in response to micro-damage. Thus, the receptor is
      crucial in skeletal mechano-transduction and in the continuous repair process.
      However, under pathophysiological conditions such as diabetes with high glucose
      concentrations or glucocorticoid-treatment the receptor is downregulated thus
      blunting the important effects it has for maintaining a healthy and strong
      skeleton.

PMID- 29587221
TI  - Structure-activity relationships of 2, 4-disubstituted pyrimidines as dual
      ERalpha/VEGFR-2 ligands with anti-breast cancer activity.
AB  - Both ERalpha and VEGFR-2 are important targets for cancer therapies. Here a
      series of 2, 4-disubstituted pyrimidine derivatives were designed, synthesized
      and evaluated as dual ERalpha/VEGFR-2 ligands. Most of the derivatives exhibited
      potent activities in both enzymatic and cellular assays. Structure-activity
      relationship studies showed that a hydrogen-bonding interaction in the head
      section is important factors for the enhancement of ERalpha-binding affinity. The
      most potent compound II-9OH, an analog of 2-(4-hydroxylphenyl)pyrimidine, was 19
      fold more efficacious than tamoxifen in MCF-7 cancer cells and exhibited the best
      ERalpha binding affinity (IC50 = 1.64 MUM) as well as excellent VEGFR-2
      inhibition (IC50 = 0.085 MUM). Furthermore, this dual targeted compound II-9OH
      exerted significantly antiestrogenic property via suppressing the expression of
      progesterone receptor (PgR) mRNA in MCF-7 cells and also showed obvious in vivo
      angiogenesis inhibitory effects in CAM assay. An induction of apoptosis and a
      decrease in cell migration, accompanied by transduction inhibition of Raf
      1/MAPK/ERK pathway, were observed in MCF-7 cells after treatment with II-9OH,
      suggesting that II-9OH is a promising candidate for the development of
      multifunctional agents targeting ERalpha and VEGFR-2 in the therapy of some
      breast cancers.

PMID- 29587222
TI  - Occupational extremely low frequency magnetic fields (ELF-MF) exposure and
      hematolymphopoietic cancers - Swiss National Cohort analysis and updated meta
      analysis.
AB  - PURPOSE: Previous studies have examined risks of leukaemia and selected lymphoid
      malignancies in workers exposed to extremely low frequency magnetic fields (ELF
      MF). Most studies evaluated hematolymphopoietic malignancies as a combined
      category, but some analyses suggested that effects may be contained to some
      specific leukaemia or lymphoma subtypes, with inconsistent results. METHODS: We
      examined exposure to ELF-MF and mortality 1990-2008 from different types of
      hematolymphopoietic cancers in the Swiss National Cohort, using a job exposure
      matrix for occupations recorded at censuses 1990 and 2000. We analysed 3.1
      million workers exposed at different levels to ELF-MF: ever-high, only-medium,
      only-low exposure using Cox proportional hazard models. We evaluated risk of
      death from acute myeloid leukaemia (AML), chronic myeloid leukaemia, lymphoid
      leukaemia, diffuse large B-cell lymphomas, follicular lymphoma, Waldenstrom's
      macroglobulinemia, multiple myeloma and Hodgkin lymphoma. RESULTS: Mortality from
      hematolymphopoietic cancers was not associated with exposure to ELF-MF with the
      exception of an increase in ever-high exposed men of myeloid leukaemias (HR 1.31,
      95% CI 1.02-1.67), and AML (HR 1.26, 95%CI 0.93-1.70). If workers had been high
      exposed during their vocational training and at both censuses, these HR increased
      to 2.24 (95%CI 0.91-5.53) and 2.75 (95%CI 1.11-6.83), respectively. CONCLUSIONS:
      Our analysis provided no convincing evidence for an increased risk of death from
      a range of hematolymphopoietic cancers in workers exposed to high or medium
      levels of ELF magnetic fields. However, we observed an increased risk of acute
      myeloid leukaemia in workers exposed to high levels for a longer duration.
      Observed risks are in line with meta-analysed previous reports on ELF-MF exposure
      and AML risk, with a summary relative risk of 1.21 (95%CI 1.08-1.37).

PMID- 29587223
TI  - Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico
      City infants, children and young adults. APOE4 carriers have higher suicide risk
      and higher odds of reaching NFT stage V at <= 40 years of age.
AB  - Exposures to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards
      are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC)
      residents have life time exposures to PM2.5 and O3 above USEPA standards. We
      investigated AD intra and extracellular protein aggregates and ultrastructural
      neurovascular pathology in 203 MMC residents age 25.36 +/- 9.23 y.
      Immunohistochemical methods were used to identify AT8 hyperphosphorilated tau
      (Htau) and 4G8 (amyloid beta 17-24). Primary outcomes: staging of Htau and
      amyloid, per decade and cumulative PM2.5 (CPM2.5) above standard. Apolipoprotein
      E allele 4 (APOE4), age and cause of death were secondary outcomes. Subcortical
      pretangle stage b was identified in an 11month old baby. Cortical tau pre
      tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases 1-2, Htau in
      substantia nigrae, auditory, oculomotor, trigeminal and autonomic systems were
      identified by the 2nd decade. Progression to NFT stages III-V was present in
      24.8% of 30-40 y old subjects. APOE4 carriers have 4.92 times higher suicide odds
      (p = 0.0006), and 23.6 times higher odds of NFT V (p < 0.0001) v APOE4 non
      carriers having similar CPM2.5 exposure and age. Age (p = 0.0062) and CPM2.5 (p =
      0.0178) were significant for developing NFT V. Combustion-derived nanoparticles
      were associated with early and progressive damage to the neurovascular unit.
      Alzheimer's disease starting in the brainstem of young children and affecting
      99.5% of young urbanites is a serious health crisis. Air pollution control should
      be prioritised. Childhood relentless Htau makes a fundamental target for
      neuroprotective interventions and the first two decades are critical. We
      recommend the concept of preclinical AD be revised and emphasize the need to
      define paediatric environmental, nutritional, metabolic and genetic risk factor
      interactions of paramount importance to prevent AD. AD evolving from childhood is
      threating the wellbeing of our children and future generations.

PMID- 29587224
TI  - Application of ultra high-performance liquid chromatography tandem mass
      spectrometry to investigate the regioselective glucuronidation of icaritin in
      vitro.
AB  - Icaritin is one of the Epimedium products with various biological activities. In
      the present study, we developed a rapid, reliable and robust UHPLC-MS/MS method
      to simultaneously determine unconjugated icaritin and its multiple glucuronides
      (icaritin-3-glucuronide, icaritin-7-glucuronide and icaritin-3,7-diglucuronide)
      in microsomal incubation systems, and applied it to study icaritin regioselective
      glucuronidation in vitro. We identified the involvement of human UDP
      glucuronosyltransferase (UGT) isoforms in icaritin metabolism and further studied
      the kinetic profiles of icaritin glucuronidation using pooled human liver
      microsomes (HLMs), pooled rat liver microsomes (RLMs), pooled human intestine
      microsomes (HIMs) and UGTs, respectively. We also evaluated regioselective
      glucuronidation of icaritin by UGT isoforms and conducted time-dependent
      experiment to elucidate the metabolic pathways for icaritin clearance. Catalytic
      efficiency of microsomes is determined according to rank orders of total
      intrinsic clearance (CLint): CLint,HLM (24.19 mL/mg/min) > CLint,RLM (13.15
      mL/mg/min) > CLint,HIM (6.43 mL/mg/min). Besides, icaritin glucuronidation is
      mediated by multiple enzymes, with UGT1A1 the principal metabolizing enzyme
      (total CLint,UGT1A1 = 6.38 mL/mg/min). As for the regioselectivity, except for
      UGT1A8 and UGT2B7, most UGT isoforms exhibit preference for the position of 3-OH
      on icaritin structure. Moreover, time-dependent conversion from monoglucuronides
      to diglucuronide indicate that icaritin-3,7-diglucuronide may be the final
      metabolite from icaritin elimination.

PMID- 29587225
TI  - Hydrogen deuterium exchange reveals changes to protein dynamics of recombinant
      human erythropoietin upon N- and O- desialylation.
AB  - Recombinant human erythropoietin (EPO) is a therapeutic glycoprotein widely used
      for treating anemia. EPO glycans carry extensive sialylation and the level of the
      modification is known to affect receptor binding, protein stability and
      pharmacokinetics. Nonetheless, a detailed understanding of the effects of
      sialylation on EPO conformation and dynamics is still lacking. Here we
      investigate the changes to EPO dynamics following enzymatic trimming of terminal
      sialic acid by amide hydrogen deuterium exchange mass spectrometry (HDX-MS). The
      results revealed that desialylation enhances structural flexibility near the
      glycosylation sites, with greater effects observed around the O-glycosylation
      site relative to the N-glycosylation sites. The affected regions are surface
      exposed loops connecting the helix bundle, which do not appear to reduce the
      thermostability of the molecule as revealed from melting measurement. Our
      findings demonstrate the feasibility of HDX-MS technique in deciphering the
      function of specific type of glycosylation that can provide novel insights into
      the role of sialylation on protein therapeutics.

PMID- 29587226
TI  - Comparative metabolites profiles of osthole in normal and osteoporosis rats using
      liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - Osthole is a derivative of coumnarin, which has been used to treat several
      diseases, including osteoporosis. To investigate the metabolite profile of
      osthole in osteoporosis rats was utilized to understand its underlying mechanisms
      of its anti-osteoporosis effect. In this study, plasma samples were collected
      from normal and osteoporosis rats after oral administration of osthole and
      analyzed to identify the metabolites of osthole by high performance liquid
      chromatography quadrupole time-of-flight mass spectrometry. By comparing the
      molecular weight and MS fragmentation of the metabolites with those of parent
      drug and reference standards, a total of 36 metabolites in plasma were
      identified. Demethylation, hydroxylation, hydroxymethylene loss and reduction,
      and subsequent glucuronidation, methylation and sulfation were the major
      metabolic pathways of osthole in both normal and osteoporosis rats. A specific
      hydration metabolic pathway was found in osteoporosis rats. These results
      provided a meaningful basis for studying the underlying mechanism of the anti
      osteoporosis effect of osthole.

PMID- 29587227
TI  - Characterization of product-related low molecular weight impurities in
      therapeutic monoclonal antibodies using hydrophilic interaction chromatography
      coupled with mass spectrometry.
AB  - Traditional SDS-PAGE method and its modern equivalent CE-SDS method are both
      widely applied to assess the purity of therapeutic monoclonal antibody (mAb) drug
      products. However, structural identification of low molecular weight (LMW)
      impurities using those methods has been challenging and largely based on
      empirical knowledges. In this paper, we present that hydrophilic interaction
      chromatography (HILIC) coupled with mass spectrometry analysis is a novel and
      orthogonal method to characterize such LMW impurities present within a purified
      mAb drug product sample. We show here that after removal of N-linked glycans, the
      HILIC method separates mAb-related LMW impurities with a size-based elution
      order. The subsequent mass measurement from a high-resolution accurate mass
      spectrometer provides direct and unambiguous identification of a variety of low
      abundance LMW impurities within a single LC-MS analysis. Free light chain, half
      antibody, H2L species (antibody possessing a single light chain) and protein
      backbone-truncated species can all be confidently identified and elucidated in
      great detail, including the truncation sites and associated post-translational
      modifications. It is worth noting that this study provides the first example
      where the H2L species can be directly detected in a mAb drug product sample by
      intact mass analysis without prior enrichment.

PMID- 29587228
TI  - The effect of NaCl stress on photosynthetic efficiency and lipid production in
      freshwater microalga-Scenedesmus obliquus XJ002.
AB  - Rapid industrialization and population growth have increased the world's energy
      demands, resulting in a shortage of conventional fossil fuels. Thus, there is an
      urgent need to develop sustainable and renewable forms of energy. Microalgae have
      emerged as a potential feedstock for biofuel production. Under stress conditions,
      lipid production is enhanced in algal cells due to changes in the lipid
      biosynthetic pathways that produce neutral lipids. In this study, we examined the
      physiological and biochemical effects of salinity stress (0.00, 0.01, 0.10, 0.15,
      0.20M) on the freshwater microalga Scenedesmus obliquus XJ002. We found that the
      biomass and the content of chlorophyll a, b and carotenoids decreased with
      increasing NaCl concentration. NaCl stress damaged the oxygen evolving complex
      (OEC) and the PSII (photosystem II) reaction center and subsequently suppressed
      electron transport at the donor and receptor sides of the reaction center,
      influencing the absorption, transfer, and application of light energy.
      Additionally, the total lipid content of cells was significantly increased under
      NaCl stress treatment. The highest lipid content (32.26%) was found in cells
      cultured in the presence of 0.20M NaCl, which was about 2.52-fold higher than
      that of cells grown in medium lacking NaCl (12.82%). In addition to providing
      insight into the physiological and biochemical responses of S. obliquus XJ002 to
      salinity stress, these findings show that lipid production, and hence biofuel
      feedstock production, can be boosted by adjusting salt levels in the growth
      medium.

PMID- 29587229
TI  - Representing a large region with few sites: The Quality Index approach for field
      studies.
AB  - Many environmental studies require the characterization of a large geographical
      region using a range of representative sites amenable to intensive study. A
      systematic approach to selecting study areas can help ensure that an adequate
      range of the variables of interest is captured. We present a novel method of
      selecting study sites representing a larger region, in which the region is
      divided into subregions, which are characterized with relevant independent
      variables, and displayed in mathematical variable space. Potential study sites
      are also displayed this way, and selected to cover the range in variables present
      in the region. The coverage of sites is assessed with the Quality Index, which
      compares the range and standard deviation of variables among the sites to that of
      the larger region, and prioritizes sites that are well-distributed (i.e. not
      clumped) in variable space. We illustrate the method with a case study examining
      relationships between agricultural land use, physiography and stream phosphorus
      (P) export, in which we selected several variables representing agricultural P
      inputs and landscape susceptibility to P loss. A geographic area of 110,000km2
      was represented with 11 study sites with good coverage of four variables
      representing agricultural P inputs and transport mechanisms taken from commonly
      available geospatial datasets. We use a genetic algorithm to select 11 sites with
      the highest possible QI and compare these, post-hoc, to our sites. This approach
      reduces subjectivity in site selection, considers practical constraints and
      easily allows for site reselection if necessary. This site selection approach can
      easily be adapted to different landscapes and study goals, as we provide an
      algorithm and computer code to reproduce our approach elsewhere.

PMID- 29587230
TI  - Oxidative stress and DNA damage in zebrafish liver due to hydroxyapatite
      nanoparticles-loaded cadmium.
AB  - This study investigated the acute and sub-acute toxicity responses in zebrafish
      following their exposure to hydroxyapatite-loaded cadmium nanoparticles (nHAP
      Cd). The results indicate that cadmium chloride (Cd2+), 20 nm nHAP-Cd (nHAP20
      Cd), and 40 nm nHAP-Cd (nHAP40-Cd) caused toxicity in zebrafish; the toxicity
      levels were in the following order: Cd2+ > nHAP20-Cd > nHAP40-Cd. Furthermore,
      nHAP-Cd showed level II grade of acute toxicity in zebrafish; the gradation was
      done on the guidelines of the Organization for Economic Co-operation and
      Development 203. We also found that Cd2+ ions and nHAP-Cd affected the
      malondialdehyde (MDA) levels and membrane permeability of zebrafish livers; these
      effects were compliant with the changes in antioxidant levels. The results of
      enzyme assays indicate the following notion: following the exposure of zebrafish
      to 0.12-0.93 mg/L nHAP-Cd, the activities of peroxidase, superoxide dismutase,
      and catalase enzymes increased significantly. Moreover, the content of anti
      superoxide anion also increased substantially. This increasing trend of enzymatic
      activity was observed until the concentration of nHAP-Cd reached 1.86 mg/L nHAP
      Cd. By increasing the concentration of both Cd2+ and nHAP-Cd, we found that
      levels of DNA damage had increased substantially in zebrafish liver; this effect
      was visualized by performing comet assay.

PMID- 29587231
TI  - Neonicotinoid pesticides in drinking water in agricultural regions of southern
      Ontario, Canada.
AB  - Because of the persistence and solubility of neonicotinoid insecticides (NNIs),
      there is concern that these compounds may contaminate sources of drinking water.
      The objective of this project was to evaluate the distribution of NNIs in raw and
      treated drinking water from selected municipalities that draw their water from
      the lower Great Lakes in areas of southern Ontario, Canada where there is high
      intensity agriculture. Sites were monitored using Polar Organic Chemical
      Integrative Samplers (POCIS) and by collecting grab samples at six drinking water
      treatment plants. Thiamethoxam, clothianidin and imidacloprid were detected in
      both POCIS and grab samples of raw water. The frequency of detection of NNIs was
      much lower in treated drinking water, but some compounds were still detected at
      estimated concentrations in the low ng L-1 range. Thiamethoxam was detected in
      one grab sample of raw drinking water at a mean concentration of 0.28 MUg L-1,
      which is above the guidelines for drinking water recommended in some
      jurisdictions, including the European Union directive on pesticide levels <0.1
      MUg L-1 in water intended for human consumption. Further work is required to
      determine whether contamination of sources of drinking water with this class of
      insecticides is a global problem in agricultural regions.

PMID- 29587232
TI  - Influence of microplastics on the accumulation and chronic toxic effects of
      cadmium in zebrafish (Danio rerio).
AB  - As the accumulation of microplastics (MPs) in the environment continues to rise,
      more concerns focus on the health risk of combined exposure to MPs and other
      contaminants. The aim of this study is to investigate the influences of MPs on
      the tissue-accumulation of cadmium (Cd) in zebrafish and explore the related
      chronic toxic effects induced by combined exposure of Cd and MPs. After co
      exposure to MPs and Cd for 3 weeks, 20 and 200 MUg/L MPs increased the
      accumulation of Cd in zebrafish livers (46% and 184%), guts (10% and 25%) and
      gills (9% and 46%). The Cd accumulation was gill > gut > liver. Comprehensive
      analyzes of biochemical biomarkers, histopathological observation and functional
      gene expression firstly demonstrated that the presence of MPs enhanced the
      toxicity of Cd on zebrafish and the combined exposure caused oxidative damage and
      inflammation in zebrafish tissues. Collectively, our results highlight the
      chronic effects of combined exposure to MPs and heavy metals.

PMID- 29587233
TI  - Characteristics of suspended particulate matter in a typical slow-moving river of
      northern China: Insight into its structure and motion behavior.
AB  - To investigate the characteristics of suspended particulate matter (SPM) in
      rivers of northern China, SPM was collected from 20 sampling sites within the
      severely polluted slow-moving Ziya River Mainstream (ZRM) and from 20 sampling
      sites within the less-polluted fast-moving Luanhe River (LR) between October and
      November of 2016. Physical and chemical attributes of river water from the ZRM
      and LR were measured; the microstructure, specific surface area and particle size
      of the SPM were also determined. The SPM had thicker organic coated layers on
      inorganic particles within the ZRM, compared with the LR, indicating strong
      interaction of the SPM with the water column. Along the ZRM length, these organic
      coated layers evolved, first plugging particle pores and then increasing in
      volume, causing the specific surface area to decrease at first and then increase.
      The presence of organic coated layers on inorganic particles greatly changed
      their particle size, density and inducing changes in their motion behavior. Such
      changes in SPM microstructure were most apparent in the slow-moving polluted ZRM.
      Given that SPM can adsorb contaminants, such as phosphorus and heavy metals, onto
      its surfaces and transport them downstream, these changes could have a profound
      impact on both sediment transport and river ecosystem function. Our results
      suggest we need to reevaluate our previous river management measures for slow
      moving polluted rivers.

PMID- 29587234
TI  - The pro-inflammatory effects of particulate matter on epithelial cells are
      associated with elemental composition.
AB  - BACKGROUND: Adverse health effects of particulate matter (PM) vary with chemical
      composition; however, evidence regarding which elements are the most detrimental
      is limited. The roof space area provides an open and stable environment for
      outdoor PM to settle and deposit. Therefore, this study used roof space PM
      samples as a proxy of residential cumulative exposure to outdoor air pollution to
      investigate their pro-inflammatory effects on human lung cells and the
      contribution of the endotoxin and chemical content. METHODS: Roof space PM
      samples of 36 different homes were collected and analysed using standardised
      techniques. We evaluated cytotoxicity and cytokine production of BEAS-2B cells
      after PM exposure using MTS and ELISA, respectively. Principle component analysis
      (PCA) and linear regression analyses were employed to assess the associations
      between cytokine production and the PM components. RESULTS: PM caused significant
      time- and dose-dependent increases in cellular cytokine production (p < 0.05).
      PCA identified four factors that explained 68.33% of the variance in the chemical
      composition. An increase in Factor 1 (+Fe, +Al, +Mn) score and a decrease in
      Factor 2 (-Ca, +Pb, +PAH) score were associated with increased interleukin (IL)-6
      (Factor 1; p = 0.010; Factor 2; p = 0.006) and IL-8 (Factor 1; p = 0.003; Factor
      2; p = 0.020) production, however, only the association with Factor 1 was evident
      after correcting for endotoxin and particle size. CONCLUSIONS: Our study provides
      novel insight into the positive associations between pro-inflammatory effects of
      roof space PM samples with Fe, Al and Mn levels.

PMID- 29587235
TI  - Toxicological interactions between mycotoxins from ubiquitous fungi: Impact on
      hepatic and intestinal human epithelial cells.
AB  - Aflatoxin B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1) and ochratoxin A
      (OTA) are toxic fungal metabolites co-occurring naturally in the environment.
      This study aimed to evaluate the toxicological interactions of these mycotoxins
      concerning additive, antagonistic and synergistic toxicity towards human cells.
      The theoretical biology-based Combination index-isobologram method was used to
      evaluate the individual and binary effect of these toxins and determine the type
      of the interaction using as models Caco-2 (intestinal) and HepG2 (hepatic) cells.
      Cytotoxicity was assessed using the MTT test at the concentrations of 0.625-20
      MUM for all the compounds. DON exerted the highest toxicity toward both cells,
      OTA and AFB1 also showed a dose-effect response, whereas no toxicity was verified
      for FB1. Synergism or antagonism effects occurred when exposing AFB1-DON and AFB1
      OTA on Caco-2 cells at higher or lower concentrations, respectively; while DON
      OTA showed synergism throughout all inhibition levels. Concerning HepG2, AFB1-DON
      exerted a strong synergism, regardless of the level; whereas AFB1-OTA had slight
      synergism/nearly additive effect; and, OTA-DON had a moderate antagonism/nearly
      additive effect. Synergistic strengths as high as a dose reduction index of 10
      for AFB1-DON were observed in hepatic cells. Taken together our findings indicate
      that the toxicological effects differ regarding the type of mycotoxins used for
      combinations and the stronger synergistic effect was observed for mixtures
      containing DON in both cells. Therefore, even though DON has not been classified
      as to its carcinogenicity to humans, this mycotoxin may present a serious threat
      to health, mainly when co-occurring in the environment.

PMID- 29587236
TI  - Ciprofloxacin-metal complexes -stability and toxicity tests in the presence of
      humic substances.
AB  - The co-contamination of ciprofloxacin (CIP) with metal ions results in alteration
      of CIP mobility, antimicrobial activity and distribution/development of the
      antibiotic-resistance genes. In this study, the stability of five CIP-Me
      complexes [Me = Al(III), Co(II), Cu(II), Fe(III), Mg] was investigated in the
      presence of humic substances (HS) at two temperatures 18 +/- 2  degrees C and 4
      +/- 1  degrees C for seven days period. The most stable complexes were CIP-Al,
      CIP-Cu, and CIP-Co with the stability constants (K) at 18  degrees C 35.5 +/- 1.4
      11.5 +/- 1.5 and 11.7 +/- 1.5 respectively. At lower temperature (4  degrees C),
      the stability constants decreased: 1-fold for CIP-Al, 14-fold for CIP-Co and 2
      fold for CIP-Cu. The presence of humic substances decreased the stability of
      complexes. The chemical reactions of Fe3+ in water at circumneutral pH resulted
      in stability alteration. The formation of CIP-Mg complexes at lower temperatures
      and in the presence of HS was limited. In ultrapure water, CIP-Me complexes
      exhibit higher toxicity towards Gram-negative Enterobacter aeruginosa (ranged
      between 0.125 and 0.5 MUg/ml). However, the presence of HS reduced the
      antimicrobial activity of CIP-Me complexes by at least 2-fold. Gram-positive
      representative, Bacillus subtilis was not affected by the presence of metal ions
      and/or HS. The toxicity toward B. subtilis for the complexes was equal to
      toxicity of CIP alone (MIC = 0.25 MUg/ml). This suggested the different
      susceptibility to CIP and its complexes.

PMID- 29587237
TI  - Isothermal microcalorimetry - A quantitative method to monitor Trypanosoma
      congolense growth and growth inhibition by trypanocidal drugs in real time.
AB  - Trypanosoma congolense is a protozoan parasite that is transmitted by tsetse
      flies, causing African Animal Trypanosomiasis, also known as Nagana, in sub
      Saharan Africa. Nagana is a fatal disease of livestock that causes severe
      economic losses. Two drugs are available, diminazene and isometamidium, yet
      successful treatment is jeopardized by drug resistant T. congolense. Isothermal
      microcalorimetry is a highly sensitive tool that can be used to study growth of
      the extracellular T. congolense parasites or to study parasite growth inhibition
      after the addition of antitrypanosomal drugs. Time of drug action and time to
      kill can be quantified in a simple way by real time heat flow measurements. We
      established a robust protocol for the microcalorimetric studies of T. congolense
      and developed mathematical computations in R to calculate different parameters
      related to growth and the kinetics of drug action. We demonstrate the feasibility
      and benefit of the method exemplary with the two standard drugs, diminazene
      aceturate and isometamidium chloride. The method and the mathematical approach
      can be translated to study other pathogenic or non-pathogenic cells if they are
      metabolically active and grow under axenic conditions.

PMID- 29587238
TI  - Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via
      suppression of sex hormone imbalances, oxidative stress, inflammation and
      apoptosis in female wistar rats.
AB  - Cisplatin (CP) is a widely used chemotherapeutic drug, effective against a
      variety of solid tumours, though its utility is limited due to its multiple organ
      toxicity. Zingerone (ZO), one of the most important components of dry ginger
      root, has several pharmacological activities, such as antioxidant, anti
      inflammatory and anti-apoptotic properties. This study aimed to investigate the
      ameliorative effect of ZO on CP-induced ovarian and uterine toxicity in female
      rats. The rats were subjected to a prophylactic oral treatment of ZO (25 and 50
      mg/kg body weight) for seven days to measure the protective effect against
      ovarian and uterine toxicity induced by a single (i.p.) of CP (7 mg/kg body
      weight) on the first day whereas the rats were sacrificed on the eighth day. The
      results showed that ZO decreased the serum FSH hormone level, increased the serum
      E2 hormone level, and also maintained the ovarian and uterine histological
      architecture and integrity. In addition, ZO obviously increased the measured
      activity of antioxidant enzymes (SOD, CAT and GPx) and the GSH content, and
      significantly reduced MDA levels. ZO was able to reduce the levels of the
      inflammatory markers NF-kappaB, TNF-alpha, IL-1beta, IL-6, COX-2 and iNOS in CP
      induced ovarian and uterine damage. It also inhibited apoptosis and reduced
      oxidative DNA damage markers by the downregulation of caspase-3 and 8-OHdG
      expression coupled with an upregulated Bcl-2 level. The results indicate that ZO
      may be beneficial in ameliorating CP-induced oxidative stress, sex hormone
      imbalances, inflammation and apoptosis in ovarian and uterine tissues of female
      rats.

PMID- 29587239
TI  - Enhanced expression of SRPK2 contributes to aggressive progression and metastasis
      in prostate cancer.
AB  - Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is
      up-regulated in multiple human tumors. However, the expression, function and
      clinical significance of SRPK2 in prostate cancer (PCa) has not yet been
      understood. We therefore aimed to determine the association of SRPK2 with tumor
      progression and metastasis in PCa patients in our present study. The expression
      of SRPK2 was detected by some public datasets and validated using a clinical
      tissue microarray (TMA) by immunohistochemistry. The association of SRPK2
      expression with various clinicopathological characteristics of PCa patients was
      subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA)
      dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation,
      migration, invasion, cell cycle progression, apoptosis and tumor growth were then
      respectively investigated using in vitro and in vivo experiments. First, public
      datasets showed that SRPK2 expression was greater in PCa tissues when compared
      with non-cancerous tissues. Statistical analysis demonstrated that high
      expression of SRPK2 was significantly correlated with a higher Gleason Score,
      advanced pathological stage and the presence of tumor metastasis in the TCGA
      Dataset (all P < 0.01). Similar correlations between SRPK2 and a higher Gleason
      Score or advanced pathological stage were also identified in the TMA (P < 0.05).
      Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free
      time of PCa patients with SRPK2 high expression was shorter than for those with
      SRPK2 low expression (P < 0.05). Second, cell function experiments in PCa cell
      lines revealed that enhanced SRPK2 expression could promote cell proliferation,
      migration, invasion and cell cycle progression but suppress tumor cell apoptosis
      in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo.
      In conclusion, our data demonstrated that SRPK2 may play an important role in the
      progression and metastasis of PCa, which suggests that it might be a potential
      therapeutic target for PCa clinical therapy.

PMID- 29587240
TI  - Tea polysaccharide inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells
      and ameliorates ovariectomy-induced osteoporosis in rats.
AB  - BACKGROUND AND PURPOSE: Tea drinking has positive effects on bone health and may
      prevent and treat osteoporosis, especially in older and postmenopausal women. Tea
      polysaccharide (TPS) is a major bioactive constituent in tea. Despite its
      profound effects on human health, whether TPS has anti-osteoporotic effects
      remains largely unknown. As such, we investigated the anti-osteoporotic effects
      of TPS. METHODS: In vitro, TPS effects on osteoclastogenesis were examined using
      osteoclast precursor RAW264.7 cells. TPS effects on osteoclastogenesis-related
      expression of marker genes and proteins were determined by gene expression and
      immunoblotting analyses, respectively. For in vivo studies, 12-week-old female
      Wistar rats were divided randomly into a sham-operated group (sham) and four
      ovariectomized (OVX) subgroups: OVX with vehicle (model) and OVX with low-,
      medium-, and high-dose TPS (0.32, 0.64 and 1.28 g/kg body weight/day,
      respectively). TPS was administered intragastrically to rats for 13 weeks. Body
      weight, blood biochemical parameters, organ weight, organ coefficients, femoral
      length, bone mineral density (BMD), biomechanical properties, and bone
      microarchitecture were documented. RESULTS: TPS inhibited osteoclast
      differentiation significantly and dose-dependently, and its inhibitory effect was
      not due to toxicity to RAW264.7 cells. TPS suppressed expression of
      osteoclastogenesis-related marker genes and proteins significantly. In in vivo
      studies, medium-dose TPS treatment ameliorated OVX-induced calcium loss
      significantly. Low-dose TPS treatment decreased the activity of acid phosphatase
      (ACP) in OVX rats significantly. In addition, TPS treatment improved other blood
      biochemical parameters and femoral biomechanical properties to a certain extent.
      More importantly, TPS treatment ameliorated bone microarchitecture in OVX rats
      strikingly because of increased cortical bone thickness and trabecular bone area
      in the femur. CONCLUSION: TPS can inhibit receptor activator nuclear factor-kappa
      B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells and ameliorate
      ovariectomy-induced osteoporosis in rats.

PMID- 29587241
TI  - Butyrate, a dietary fiber derivative that improves irinotecan effect in colon
      cancer cells.
AB  - A diet rich in fiber is associated with a low risk of developing colorectal
      cancer. Dietary fiber fermentation by intestinal microflora results in the
      production of butyrate, which has been reported as a chemopreventive agent and a
      histone deacetylase inhibitor (HDACi). Irinotecan is used as second-line
      treatment and induces adverse effects with serious life-threatening toxicities in
      at least 36% of patients. Our study intends to find a synergy that could improve
      the efficacy and decrease the toxicity of chemotherapy. Results demonstrate that
      milimolar concentrations of butyrate has an anti-proliferative effect in all
      three colon cancer cell lines under study, leading to a decrease on cell
      viability, expression of P21, P53 and beta-catenin, being able to modulate P
      glycoprotein activity and to induce apoptosis by modulation of BAX/BCL-2 ratio.
      Combined therapy has a cytotoxic potential, resulting in a synergistic effect,
      and allows a reduction in irinotecan concentration needed to reduce IC50. This
      potential was verified in terms of cell viability and death, cell cycle and
      expression of P21 and P53. Butyrate and irinotecan act synergistically in the
      three cancer cell lines, despite the different genetic background and location,
      and inhibited tumor growth in a xenograft model. Butyrate is able to influence
      the mechanism of LS1034 cell line chemoresistance. Butyrate in combination with
      chemotherapeutic agents has an important role for the treatment of colorectal
      cancer. Such understanding can guide decisions about which patients with
      colorectal cancer may benefit from therapy with butyrate demonstrating the
      important role of diet in colorectal cancer treatment.

PMID- 29587242
TI  - Anthocyanins as a potential pharmacological agent to manage memory deficit,
      oxidative stress and alterations in ion pump activity induced by experimental
      sporadic dementia of Alzheimer's type.
AB  - Anthocyanins (ANT) are polyphenolic flavonoids with antioxidant and
      neuroprotective properties. This study evaluated the effect of ANT treatment on
      cognitive performance and neurochemical parameters in an experimental model of
      sporadic dementia of Alzheimer's type (SDAT). Adult male rats were divided into
      four groups: control (1 ml/kg saline, once daily, by gavage), ANT (200 mg/kg,
      once daily, by gavage), streptozotocin (STZ, 3 mg/kg) and STZ plus ANT. STZ was
      administered via bilateral intracerebroventricular (ICV) injection (5 MUl). ANT
      were administered after ICV injection for 25 days. Cognitive deficits (short-term
      memory and spatial memory), oxidative stress parameters, and acetylcholinesterase
      (AChE) and Na+-K+-ATPase activity in the cerebral cortex and hippocampus were
      evaluated. ANT treatment protected against the worsening of memory in STZ-induced
      SDAT. STZ promoted an increase in AChE and Na+-K+-ATPase total and isoform
      activity in both structures; ANT restored this change. STZ administration induced
      an increase in lipid peroxidation and decrease in the level of antioxidant
      enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx), in the cerebral cortex; ANT significantly attenuated these
      effects. In the hippocampus, an increase in reactive oxygen species (ROS),
      nitrite and lipid peroxidation levels, and SOD activity and a decrease in CAT and
      GPx activity were seen after STZ injection. ANT protected against the changes in
      ROS and antioxidant enzyme levels. In conclusion, the present study showed that
      treatment with ANT attenuated memory deficits, protected against oxidative damage
      in the brain, and restored AChE and ion pump activity in an STZ-induced SDAT in
      rats.

PMID- 29587243
TI  - Serum calcium levels and neuropsychological performance in depression and matched
      healthy controls: Reversal of correlation a marker of the aging cognitive clock?
AB  - BACKGROUND: Major depressive disorder (MDD) is associated with cognitive
      impairment, that might be related to disturbed calcium homeostasis. Calcium
      related processes have also been implicated in age related cognitive decline.
      Since serum calcium and brain interstitial fluids maintain long-term equilibrium
      under normal physiological states, serum calcium levels could affect neuronal and
      hence cognitive function. High serum calcium has been associated with cognitive
      decline in geriatric populations, whereas evidence for MDD and healthy
      populations is less consistent. METHODS: Differences in neuropsychological (NPS)
      performance and their relationship with serum calcium (total, ionized, total to
      ionized ratio) in (partially) remitted MDD patients (n = 59) and healthy controls
      (HC) (n = 59) individually matched for age, gender and education (age-range 19-60
      years) were examined. Modulation of study parameters and their interaction by the
      factor age was investigated, with subgroups young and old divided at median = 37
      years. Participants provided blood samples and completed an extensive NPS test
      battery. RESULTS: MDD showed significantly poorer NPS performance compared to HC.
      Serum calcium associated positively with NPS performance in HC and negatively in
      MDD for entire age-range samples. While younger MDD and HC showed positive NPS
      calcium correlations, older MDD and HC exhibited negative NPS-calcium
      correlations ('correlation reversal'). Age had a significant effect on cognition
      and ionized calcium and interacted with illness-status, with an exaggerated
      influence on cognition in MDD compared to HC. CONCLUSIONS: The results place
      calcium 'correlation reversal' to early middle-age time window, which may be
      accelerated for MDD and highlight the central role of calcium pathways in normal
      and pathological cognitive aging.

PMID- 29587244
TI  - Epigenetic regulation of vascular NADPH oxidase expression and reactive oxygen
      species production by histone deacetylase-dependent mechanisms in experimental
      diabetes.
AB  - Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox)
      contribute to structural-functional alterations of the vascular wall in diabetes.
      Epigenetic mechanisms, such as histone acetylation, emerged as important
      regulators of gene expression in cardiovascular disorders. Since their role in
      diabetes is still elusive we hypothesized that histone deacetylase (HDAC)
      dependent mechanisms could mediate vascular Nox overexpression in diabetic
      conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were
      randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA), a pan
      HDAC inhibitor. In vitro studies were performed on a human aortic smooth muscle
      cell (SMC) line. Aortic SMCs typically express Nox1, Nox4, and Nox5 subtypes.
      HDAC1 and HDAC2 proteins along with Nox1, Nox2, and Nox4 levels were found
      significantly elevated in the aortas of diabetic mice compared to non-diabetic
      animals. Treatment of diabetic mice with SAHA mitigated the aortic expression of
      Nox1, Nox2, and Nox4 subtypes and NADPH-stimulated ROS production. High
      concentrations of glucose increased HDAC1 and HDAC2 protein levels in cultured
      SMCs. SAHA significantly reduced the high glucose-induced Nox1/4/5 expression,
      ROS production, and the formation malondialdehyde-protein adducts in SMCs.
      Overexpression of HDAC2 up-regulated the Nox1/4/5 gene promoter activities in
      SMCs. Physical interactions of HDAC1/2 and p300 proteins with Nox1/4/5 promoters
      were detected at the sites of active transcription. High glucose induced histone
      H3K27 acetylation enrichment at the promoters of Nox1/4/5 genes in SMCs. The
      novel data of this study indicate that HDACs mediate vascular Nox up-regulation
      in diabetes. HDAC inhibition reduces vascular ROS production in experimental
      diabetes, possibly by a mechanism involving negative regulation of Nox
      expression.

PMID- 29587246
TI  - Effect of different designs of ankle-foot orthoses on gait in patients with
      stroke: A systematic review.
AB  - BACKGROUND: Ankle foot orthoses (AFOs) are used to improve the gait of patients
      with stroke. RESEARCH QUESTION: The current review aimed at evaluating the
      efficacy of different designs of AFOs and comparison between them on the gait
      parameters of individuals with hemiplegic stroke. METHODS: The search strategy
      was based on the population intervention comparison outcome (PICO) method. A
      search was performed in PubMed, ISI Web of Knowledge, Scopus, Science Direct, and
      Google Scholar databases. RESULTS: A total of 27 articles were found for the
      final evaluation. All types of AFOs had positive effects on ankle kinematic in
      the first rocker and swing phases, but not on knee kinematics in the swing phase,
      hip kinematics or the third rocker function. All trials, except two, assessed
      immediate or short-term effects only. The articulated passive AFO compared with
      the non-articulated passive AFO had better effects on some aspects of the gait of
      patients with hemiplegia following stroke, more investigations are needed in this
      regard though. SIGNIFICANCE: An ankle-foot orthosis can immediately improve the
      dropped foot in the stance and swing phases. The effects of long-term usage and
      comparison among the different types of AFOs need to be evaluated.

PMID- 29587245
TI  - Mitochondrial ROS cause motor deficits induced by synaptic inactivity:
      Implications for synapse pruning.
AB  - Developmental synapse pruning refines burgeoning connectomes. The basic
      mechanisms of mitochondrial reactive oxygen species (ROS) production suggest they
      select inactive synapses for pruning: whether they do so is unknown. To begin to
      unravel whether mitochondrial ROS regulate pruning, we made the local
      consequences of neuromuscular junction (NMJ) pruning detectable as motor deficits
      by using disparate exogenous and endogenous models to induce synaptic inactivity
      en masse in developing Xenopus laevis tadpoles. We resolved whether: (1) synaptic
      inactivity increases mitochondrial ROS; and (2) chemically heterogeneous
      antioxidants rescue synaptic inactivity induced motor deficits. Regardless of
      whether it was achieved with muscle (alpha-bungarotoxin), nerve (alpha
      latrotoxin) targeted neurotoxins or an endogenous pruning cue (SPARC), synaptic
      inactivity increased mitochondrial ROS in vivo. The manganese porphyrins MnTE-2
      PyP5+ and/or MnTnBuOE-2-PyP5+ blocked mitochondrial ROS to significantly reduce
      neurotoxin and endogenous pruning cue induced motor deficits. Selectively
      inducing mitochondrial ROS-using mitochondria-targeted Paraquat (MitoPQ)
      recapitulated synaptic inactivity induced motor deficits; which were
      significantly reduced by blocking mitochondrial ROS with MnTnBuOE-2-PyP5+. We
      unveil mitochondrial ROS as synaptic activity sentinels that regulate the
      phenotypical consequences of forced synaptic inactivity at the NMJ. Our novel
      results are relevant to pruning because synaptic inactivity is one of its
      defining features.

PMID- 29587247
TI  - The nanostructure of porous cobalt coatings deposited by magnetron sputtering in
      helium atmosphere.
AB  - In this work, (scanning) transmission electron microscopy has been used to study
      the nanostructure of porous cobalt coatings obtained by magnetron sputtering
      using helium as process gas. This nanostructure consists of closed pores of
      different nanometric size (about 4-20 nm) that are distributed all over a
      nanocrystalline Co matrix and filled with the deposition gas. Spatially resolved
      electron energy-loss spectroscopy analysis was applied to measure and map, with
      high lateral resolution, the relevant physical properties (density, pressure and
      He-K edge shift) of helium trapped inside these individual nanopores, in order to
      provide new insights about the growth mechanism involved in such systems. In
      particular, a coefficient of proportionality, C = 0.039 eV nm3, between the blue
      shift of the He K-edge and the He density has been found. In addition, very high
      He densities (10-100 at./nm3) and pressures in the gigapascal range (0.05-5.0
      GPa) have been measured. The linear dependence of these parameters as a function
      of the inverse radii obeying to the Laplace-Young law for most of the pores
      suggests that their formation during the coating's growth takes place in regime
      of elastic deformation of the Co matrix.

PMID- 29587248
TI  - How do medical and nursing students experience emotional challenges during
      clinical placements?
AB  - Objectives: To investigate which kinds of situations medical and nursing students
      found emotionally challenging during their undergraduate education, and how they
      managed their experiences. Methods: This study used an exploratory research
      design. We gathered qualitative data using an open-ended questionnaire
      distributed to students in the middle and at the end of their education. In
      total, 49 nursing and 65 medical students participated. Also, five students were
      interviewed individually to acquire richer data. Data were analysed using
      narrative thematic analysis. Results: Medical and nursing students experienced a
      range of situations during their undergraduate education that they found
      emotionally challenging, mainly during clinical placements. The students'
      narratives concerned confronting patients' illness and death, unprofessional
      behaviour among healthcare professionals, dilemmas regarding patient treatment,
      students relating to patients as individuals and not diagnoses, and using
      patients for their own learning. The narratives concerned both the formal and the
      hidden curriculum, i.e., what is included in the profession (confronting illness
      and death), and what is not (unprofessional behaviour among healthcare
      professionals). Students managed their experiences by talking to trusted peers or
      supervisors, and by getting used to these situations. Conclusions: Despite the
      different knowledge, experiences, and conditions for medical and nursing
      students, our findings suggest that their experiences of emotional challenges are
      similar. Support and opportunities to talk about these experiences are important.
      Teachers, supervisors, and students need to be aware that students might
      experience emotionally difficult situations, and that the students need time for
      reflection and support.

PMID- 29587249
TI  - Activation of Adenylyl Cyclase Causes Stimulation of Adenosine Receptors.
AB  - BACKGROUND/AIMS: Signaling of Gs protein-coupled receptors (GsPCRs) is
      accomplished by stimulation of adenylyl cyclase, causing an increase of the
      intracellular cAMP concentration, activation of the intracellular cAMP effectors
      protein kinase A (PKA) and Epac, and an efflux of cAMP, the function of which is
      still unclear. METHODS: Activation of adenylyl cyclase by GsPCR agonists or
      cholera toxin was monitored by measurement of the intracellular cAMP
      concentration by ELISA, anti-phospho-PKA substrate motif phosphorylation by
      immunoblotting, and an Epac-FRET assay in the presence and absence of adenosine
      receptor antagonists or ecto-nucleotide phosphodiesterase/pyrophosphatase2
      (eNPP2) inhibitors. The production of AMP from cAMP by recombinant eNPP2 was
      measured by HPLC. Extracellular adenosine was determined by LC-MS/MS,
      extracellular ATP by luciferase and LC-MS/MS. The expression of eNPP isoenzymes 1
      3 was examined by RT-PCR. The expression of multidrug resistance protein 4 was
      suppressed by siRNA. RESULTS: Here we show that the activation of GsPCRs and the
      GsPCRs-independent activation of Gs proteins and adenylyl cyclase by cholera
      toxin induce stimulation of cell surface adenosine receptors (A2A or A2B
      adenosine receptors). In PC12 cells stimulation of adenylyl cyclase by GsPCR or
      cholera toxin caused activation of A2A adenosine receptors by an autocrine
      signaling pathway involving cAMP efflux through multidrug resistance protein 4
      and hydrolysis of released cAMP to AMP by eNPP2. In contrast, in PC3 cells
      cholera toxin- and GsPCR-induced stimulation of adenylyl cyclase resulted in the
      activation of A2B adenosine receptors. CONCLUSION: Our findings show that
      stimulation of adenylyl cyclase causes a remarkable activation of cell surface
      adenosine receptors.

PMID- 29587250
TI  - Efficacy of Fine-Needle Aspiration Cytology in the Diagnosis of Tuberculous
      Cervical Lymphadenitis.
AB  - OBJECTIVE: This study assesses the role of fine-needle aspiration cytology (FNAC)
      in the diagnosis of tuberculous lymphadenitis (TL) in comparison with histology
      and bacteriology findings. STUDY DESIGN: We undertook a descriptive retrospective
      study of 937 FNAC specimens from 851 patients with cervical lymph nodes. The FNAC
      findings were then compared to histopathology and bacteriology. RESULTS: Of the
      937 aspirates, the cytopathological diagnoses consisted of 426 (55.9%) TL, 185
      (24.3%) reactive lymphoid hyperplasia, 18 (2.3%) suppurative inflammation, 78
      (10.2%) malignant metastatic tumor, and 54 (7%) lymphoma. Of the 426 TL cases,
      171 were diagnosed by FNAC combined with bacteriological examination. In this
      group, 22 cases were found to be positive on Ziehl-Neelsen stain and 16 by
      culture. A histopathology report was available for 62 cases. Compared to
      histopathology, the overall diagnostic sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) of FNAC in the
      diagnosis of cervical TL were, respectively, 96.77, 100, 100, and 96.67%. When
      comparing bacteriology to histopathology, these values were 97.44, 100, 100, and
      91.67%. CONCLUSION: Our study shows that FNAC is a sensitive and specific tool
      for the diagnosis of cervical TL.

PMID- 29587251
TI  - Pregnancy Outcomes in French Hemodialysis Patients.
AB  - BACKGROUND: Pregnancy in hemodialysis (HD) women is a rare event and often
      associated with maternal and fetal complications. Scarcity of available data from
      large cohorts impedes fair medical counseling. METHODS: This is a descriptive,
      retrospective, multi-centric study. Pregnant women on HD during the period from
      1985 to 2015 in France were included. The primary outcome was a living infant
      discharged from hospital, while secondary outcomes included gestational age and
      birth weight. RESULTS: We identified 100 pregnancies in 84 women on HD, from 41
      centers. Chronic HD was initiated during pregnancy for 17.7% (14/79) of patients
      explaining a 19.8% prevalence of catheter (19/96) and a preserved residual
      diuresis for 50% of pregnancy (43/86). Seventy-six (89.4%) women performed daily
      dialysis during the third trimester (6 times per week). Our primary outcome was
      met for 78% of newborns with a mean gestational age of 33.2 +/- 3.9 weeks and a
      mean birth weight of 1,719 +/- 730 g. CONCLUSIONS: Our study is one of the
      largest series of -pregnancies in HD patients. Despite recent progresses, these
      pregnancies remain at high risk, reinforcing the need for an early nephrologist
      obstetrician skilled team co-management.

PMID- 29587252
TI  - Fats in Foods: Current Evidence for Dietary Advice.
AB  - Current discussion of the importance of food fats in the risk of coronary heart
      disease (CHD) often suffers from preconceptions, misunderstandings, insufficient
      knowledge, and selective reasoning. As a result, the sustained controversy about
      dietary fat recommendations can be contradictory and confusing. To clarify some
      of these issues, the International Expert Movement to Improve Dietary Fat Quality
      in cooperation with the International Union of Nutritional Sciences (IUNS)
      organized a symposium at the 21st meeting of the IUNS, October 17, 2017, Buenos
      Aires, Argentina, to summarize the key scientific evidence underlying the
      controversy on the relationship between the saturated and unsaturated fat
      consumption and CHD risk. Presenters also discussed, using examples, the
      rationale for and implications of the partial replacement of foods rich in
      saturated fats by those rich in unsaturated fats. Presentations included
      strategies to fit healthier fats into meals. This report summarizes the symposium
      presentations.

PMID- 29587253
TI  - Early and One-Year Outcomes of Acute Stroke in the Industrial Region of Poland
      During the Decade 2006-2015: The Silesian Stroke Registry.
AB  - BACKGROUND: Poland, classified as a high-income country, is still considered to
      have a high cardiovascular risk population. During the last decade, the standards
      of care in acute stroke (AS) had markedly improved; thus, we aimed to assess
      whether and how it translated into early and late outcomes. METHODS: Silesian
      Stroke Registry was created from the administrative database of the public,
      obligatory, health -insurer in Poland. The AS cases were selected based on
      primary diagnosis coded in ICD-10 as I60-I64 for years 2006-2015 (n = 120,844).
      Index hospitalization together with data on re-hospitalizations, procedures,
      ambulatory visits, rehabilitation and all-cause deaths in a 1-year follow-up were
      analyzed. RESULTS: The rates of admissions per 100,000 adult population varied
      between 41-47 for haemorrhagic and 257-275 for ischaemic stroke with substantial
      decrease in almost all age groups except for the oldest patients. In ischaemic
      stroke, thrombolytic therapy raised from 0 to 8.8% in 2015, along with
      significant trends of decreasing 30-day (from 20 to 16%) and 12-month (from 35 to
      31%) case fatality. In haemorrhagic stroke, case fatality had not changed. After
      ischaemic stroke, 12-month readmissions due to AS declined from 11-12% in 2006
      2009 to 9% in 2010-2014. The percentage of patients benefiting from
      rehabilitation increased from 24 to 32%. CONCLUSIONS: In a large population of
      industrial province, we showed recent, positive trends in AS admissions,
      treatment and 1-year outcomes. Development of stroke unit networks and increase
      in thrombolytic treatment were at least in part responsible for survival
      improvement and reduction of recurrence of AS. However, case-fatality and stroke
      recurrence remain high compared to those of other developed countries.

PMID- 29587254
TI  - Evaluation of the FreeStyle(r) Libre Flash Glucose Monitoring System in Children
      and Adolescents with Type 1 Diabetes.
AB  - BACKGROUND/AIMS: The FreeStyle(r) Libre Flash Glucose Monitoring System (FGM,
      Abbott) measures glucose concentrations in the interstitial fluid for up to 14
      days. It has been approved for use in children aged > 4 years in January 2016.
      Experience in children is still limited. We evaluated the accuracy and usability
      of the FGM in children with type 1 diabetes mellitus (DM). METHODS: 67 children
      with type 1 DM (35 girls), aged 4-18 years, were included. Subjects wore a sensor
      on the back of their upper arm. For the first 14 days, they regularly measured
      capillary blood glucose (BG) with their usual BG meter (Accu-Chek(r) Mobile
      [ACM], Roche [n = 24]; Contour(r) Next Link [CNL], Bayer [n = 26]; OneTouch(r)
      Verio(r) IQ [OTV], LifeScan [n = 17]) followed by a sensor glucose (SG) scanning.
      SG readings were compared to BG measurements by consensus error grid (CEG)
      analysis; the mean difference (MD), the mean relative difference (MRD), the mean
      absolute difference (MAD), and the mean absolute relative difference (MARD) were
      calculated. After 14 days, subjects were asked to fill in a questionnaire on the
      usability of the FGM. RESULTS: 2,626 SG readings were paired with BG results. FGM
      readings were highly correlated with BG (r = 0.926, p < 0.001). 80.3% of the data
      pairs were in zone A (= no effect on clinical action) and 18.4% were in zone B (=
      altered clinical action with little or no effect on the clinical outcome) of the
      CEG. Overall MD was +7.5 mg/dL; MD varied with the BG meter: ACM +10.4 mg/dL, CNL
      +14.2 mg/dL, OTV -3.6 mg/dL (p < 0.001). Overall, MARD was 16.7%. We observed a
      large interindividual variability in the accuracy parameters. MD and MRD were
      inversely related to BMI (r = -0.261 [p < 0.05]; r = -0.266 [p < 0.05],
      respectively). MARD was inversely related to age (r = -0.266 [p < 0.05]). Twenty
      nine patients (43.3%) reported sensor problems, mainly early detachment of the
      sensor. Nonetheless, the usability questionnaire indicated high levels of
      satisfaction. CONCLUSIONS: Our results showed a reasonable agreement between the
      FGM SG readings and capillary BG measurements in children. There was, however, a
      large interindividual variability. The wearing of the sensor requires special
      attention. Further studies in children are imperative in order to document the
      accuracy and safety of the FGM in the paediatric population.

PMID- 29587255
TI  - Behaviour and Ecology of Male Aye-Ayes (Daubentonia madagascariensis) in the
      Kianjavato Classified Forest, South-Eastern Madagascar.
AB  - Previous studies found that aye-ayes (Daubentonia madagascariensis) consume a
      variety of non-invertebrate resources, supporting the hypothesis that aye-ayes
      are too large-bodied to focus feeding efforts on insects. However, these
      conclusions were based on introduced populations, with little known about aye-aye
      behaviour and ecology in its natural habitat. This study investigates activity
      budgets, diet, and home range/territories of 2 male aye-ayes in the Kianjavato
      Classified Forest, a disturbed forest in south-eastern Madagascar, from October
      2013 to October 2014. We used radiotelemetry and focal-animal sampling methods to
      collect behavioural data. We recorded GPS coordinates of the focal animal every
      20 min, calculating the home range size for each individual. Results showed that
      male aye-ayes spent most of their time feeding and travelling. Their feeding time
      primarily focussed on larvae and adult insects from various substrates, and to a
      lesser extent Canarium spp. seeds. Home range sizes of the 2 males varied between
      individuals, overlapped greatly, and appeared to be related to the location of
      females. Our findings indicate that aye-aye behaviours are strongly indicative of
      insect-centric feeding ecology.

PMID- 29587256
TI  - Protein Biomarkers in Asthma.
AB  - Asthma is a chronic disabling respiratory disease that can be triggered by a
      variety of factors, including allergens, respiratory infections, psychological
      factors, occupational agents, exercise, atmospheric pollutants, and drugs. The
      asthma syndrome has been treated for decades according to a "one-fits-all"
      treatment strategy based on bronchodilators and steroids. With the availability
      of new forms of treatment targeting the different pathomechanisms of the asthma
      syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the
      interest in biomarkers that can dis criminate different forms of asthma according
      to their pathomechanisms has increased. This review attempts to provide an
      overview of protein biomarkers in asthma and how they might be used to
      discriminate different forms of asthma that may respond positively to
      sophisticated new targeted therapies.

PMID- 29587257
TI  - A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular
      Stroke Therapy in a Regional Stroke-Network.
AB  - BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled
      trials of endovascular stroke therapies (EVT) in stroke patients with large
      vessel occlusion, different approaches to speed up the workflow for EVT
      candidates are currently being implemented worldwide. We aimed to assess the
      effect of a simple stroke network-wide workflow improvement project, primarily
      focusing on i.v. thrombolysis, on process times for patients undergoing EVT.
      METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow
      improvement program for i.v. thrombolysis with the main components of
      implementing a binding team-based algorithm at every stroke unit of the regional
      network, educating all stroke teams about non-technical skills and providing a
      stroke-specific simulation training. Before and after the intervention we
      recorded periprocedural process times, including patients undergoing EVT at the 3
      EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n =
      184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we
      observed a relevant shortening of the median time from symptom onset to EVT
      specifically in patients requiring secondary transfer by almost an hour (300 min,
      25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p =
      0.117), including a reduction of the median door-to-groin time at the EVT-capable
      center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR
      27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable
      center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR
      83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable
      heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show
      that a simple network-wide workflow improvement program primarily directed at
      fast i.v. thrombolysis also accelerates process times for EVT candidates and is a
      promising measure to improve the performance of an entire stroke network.

PMID- 29587258
TI  - Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum
      from Patients with Peripheral Artery Diseases.
AB  - BACKGROUND/AIMS: Aging of the arterial endothelial cells results in the
      appearance of their inflammatory phenotype, which may predispose patients to the
      acceleration of arteriosclerosis. We studied the effect of serum from patients
      with peripheral artery disease (PAD) on the senescence of human aortic
      endothelial cells (HAEC) and how that process is modulated by sulodexide.
      METHODS: HAEC replicative aging in vitro was studied in the presence of 10% PAD
      serum (PAD Group) or10%PAD serum and Sulodexide 0.5 LRU/mL (PAD-SUL group). In
      control group cells were cultured in medium supplemented with 10% fetal bovine
      serum. All studied parameters were evaluated at the beginning and at the end of
      the study, in all experimental groups. Population doubling time (PDT) was studied
      from the cells growth rate after repeated passages, and senescence-associated
      beta- galactosidase activity (SA-beta gal activity) was measured with the
      fluorescence flow cytometry. Expression of IL6, vWF, p21 and p53 genes was
      measured with the real-time polymerase chain reaction (Real-Time PCR).
      Concentrations of IL6 and vWF were measured with the standard ELISA kits.
      RESULTS: PAD serum accelerated the senescence of HAEC as reflected by increased,
      compared to control, expression of the IL6 gene (+43%, p<0.05) vWF gene (+443%,
      p<0.01), p21 gene (+ 124%, p<0.01) and p53 gene (+ 85%, p<0.01). Secretion of IL6
      and vWF was higher in that group: + 101%, p<0.01 and + 78%, p<0.01, respectively,
      as compared to control. Also, SA-beta gal activity was higher in the PAD group
      (+33%, p<0.05) than in the control group. In the PAD group PDT was longer (+108%,
      p<0.01) as compared to control. Simultaneous use of Sulodexide with PAD serum
      significantly reduced all the above described senescent changes in HAEC.
      CONCLUSIONS: PAD serum accelerates the aging of HAEC which may result in the
      faster progression of arteriosclerosis. Sulodexide reduces PAD induced senescence
      of HAEC, which results in lower inflammatory and thrombogenic activity of these
      cells.

PMID- 29587259
TI  - Kruppel-Like Factor 4 Inhibits Pancreatic Cancer Epithelial-to-Mesenchymal
      Transition and Metastasis by Down-Regulating Caveolin-1 Expression.
AB  - BACKGROUND/AIMS: Kruppel-like factor 4 (KLF4), a member of the KLF family of zinc
      finger transcription factors, has been identified as a tumor suppressor gene in a
      variety of tumors. However, the molecular mechanisms by which KLF4 inhibits
      epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic cancer
      remain unclear. METHODS: KLF4 expression in pancreatic cancer was analyzed using
      public datasets (Oncomine and The Cancer Genome Atlas). The expression of KLF4,
      caveolin-1 (Cav-1), E-cadherin, and vimentin, and their correlations with
      clinicopathological characteristics were evaluated by immunohistochemistry in
      pancreatic cancer tissues. The biological functions and underlying mechanisms of
      KLF4 expression on EMT and metastasis were also investigated in vitro and in
      vivo. RESULTS: Public datasets showed that KLF4 expression was significantly
      decreased in pancreatic cancer and correlated with the depth of invasion and
      disease stage. The expression of KLF4, Cav-1, E-cadherin, and vimentin protein in
      pancreatic cancer tissues was closely associated with pathological grade, disease
      stage, and metastasis. KLF4 expression was also positively correlated with E
      cadherin expression and negatively correlated with vimentin expression, whereas
      Cav-1 expression was negatively associated with E-cadherin expression and
      positively correlated with vimentin expression. Knockdown of KLF4 expression
      promoted EMT and facilitated pancreatic cancer cell growth and metastasis in
      vitro and in vivo. In addition, immunohistochemistry (IHC) results indicated that
      KLF4 expression was negatively correlated with Cav-1 expression. Furthermore,
      down-regulating KLF4 expression increased Cav-1 and vimentin expression and
      decreased E-cadherin expression. Mechanistically, KLF4 could transcriptionally
      inhibit Cav-1 expression by binding directly to the promoter domain of Cav-1.
      CONCLUSIONS: KLF4 inhibits pancreatic cancer EMT and metastasis by down
      regulating Cav-1 expression, suggesting that the KLF4/Cav-1 signaling pathway may
      be a novel diagnostic and therapeutic target.

PMID- 29587260
TI  - Verbascoside Alleviates Atopic Dermatitis-Like Symptoms in Mice via Its Potent
      Anti-Inflammatory Effect.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease
      characterized by the interplay between multiple genetic and environmental
      factors. The pathogenesis of AD remains incompletely understood. Treatment with
      topical steroids for chronic AD symptoms has severe side effects and so a new
      treatment is required. Verbascoside is a hydrophilic phenylethanoid glycoside
      with antioxidant, anti-inflammatory properties. METHODS: Verbascoside was
      evaluated in AD-like lesions induced by the repetitive and alternative
      application of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Overall
      symptomatic score and serological and molecular changes of the skin lesions were
      investigated. RESULTS: Verbascoside relieved the overall AD-like symptoms such as
      scratching behavior and skin lesion severity. At whole-body level, verbascoside
      significantly reduced DNCB-induced IgE and Th2 cytokines in the peripheral blood.
      At the skin lesion site, verbascoside also inhibited DNCB-induced production of
      proinflammatory cytokine TNF-alpha, IL-6, and IL-4 mRNA. In a human monocyte THP
      1 model, verbascoside could suppress DNCB-induced upregulation of CD86 and CD54
      at the cell surface, the secretion of the proinflammatory cytokines TNF-alpha and
      IL-6, and the activation of NFkappaB signaling in a dose-dependent manner.
      CONCLUSION: Our results demonstrate that verbascoside could be a potential
      therapeutic agent for the treatment of AD.

PMID- 29587261
TI  - High Frequency of Copy-Neutral Loss of Heterozygosity in Patients with
      Myelofibrosis.
AB  - Myelofibrosis is the rarest and most severe type of Philadelphia-negative
      classical myeloproliferative neoplasms. Although mutually exclusive driver
      mutations in JAK2, MPL, or CALR that activate JAK-STAT pathway have been related
      to the pathogenesis of the disease, chromosome abnormalities have also been
      associated with the phenotype and prognosis of the disease. Here, we report the
      use of a chromosomal microarray platform consisting of both oligo and SNP probes
      to improve the detection of chromosome abnormalities in patients with
      myelofibrosis. Sixteen patients with myelofibrosis were tested, and the results
      were compared to karyotype analysis. Driver mutations in JAK2, MPL, or CALR were
      investigated by PCR and MLPA. Conventional cytogenetics revealed chromosome
      abnormalities in 3 out of 16 cases (18.7%), while chromosomal microarray analysis
      detected copy-number variations (CNV) or copy-neutral loss of heterozygosity (CN
      LOH) alterations in 11 out of 16 (68.7%) patients. These included 43 CN-LOH, 14
      deletions, 1 trisomy, and 1 duplication. Ten patients showed multiple chromosomal
      abnormalities, varying from 2 to 13 CNVs or CN-LOHs. Mutational status for JAK2,
      CALR, and MPL by MLPA revealed a total of 3/16 (18.7%) patients positive for the
      JAK2 V617F mutation, 9 with CALR deletion or insertion and 1 positive for MPL
      mutation. Considering that most of the CNVs identified were smaller than the
      karyotype resolution and the high frequency of CN-LOHs in our study, we propose
      that chromosomal microarray platforms that combine oligos and SNP should be used
      as a first-tier genetic test in patients with myelofibrosis.

PMID- 29587262
TI  - Whole-Genome Linkage Analysis with Whole-Exome Sequencing Identifies a Novel
      Frameshift Variant in NEFH in a Chinese Family with Charcot-Marie-Tooth 2: A
      Novel Variant in NEFH for Charcot-Marie-Tooth 2.
AB  - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common
      neurodegenerative disorder of the peripheral nervous system. More than 50
      genes/loci were found associated with the disease. We found a family with
      autosomal-dominant CMT2. OBJECTIVE: To reveal the pathogenic gene of the family
      and further investigate the function of the variant. METHODS: DNA underwent whole
      genome linkage analysis for all family members and whole-exome sequencing for 2
      affected members. Neurofilament light polypeptide and wild-type or mutant
      neurofilament heavy polypeptide (NEFH) were co-transfected into SW13 (vim-)
      cells. The nefh-knockdown zebrafish model was produced by using morpholino
      antisense oligonucleotides. RESULTS: We identified a novel insertion variant
      (c.3057insG) in NEFH in the family. The variant led to the loss of a stop codon
      and an extended 41 amino acids in the protein. Immunofluorescence results
      revealed that mutant NEFH disrupted the neurofilament network and induced
      aggregation of NEFH protein. Knockdown of nefh in zebrafish caused a slightly or
      severely curled tail. The motor ability of nefh-knockdown embryos was impaired or
      even absent, and the embryos showed developmental defects of axons in motor
      neurons. The abnormal phenotype and axonal developmental defects could be rescued
      by injection of human wild-type but not human mutant NEFH mRNA. CONCLUSIONS: We
      identified a novel stop loss variant in NEFH that is likely pathogenic for CMT2,
      and the results provide further evidence for the role of an aberrant assembly of
      neurofilament in CMT.

PMID- 29587263
TI  - A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic
      Pulmonary Fibrosis.
AB  - BACKGROUND: Two therapeutic options are currently available for patients with
      mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib.
      To date, there is still insufficient data on the efficacy of these 2 agents in
      patients with more severe disease. OBJECTIVES: This national, multicenter,
      retrospective real-life study was intended to determine the impact of nintedanib
      on the treatment of patients with severe IPF. METHODS: All patients included had
      severe IPF and had to have at least 6 months of follow-up before and at least 6
      months of follow-up after starting nintedanib. The aim of the study was to
      compare the decline in lung function before and after treatment. Patient survival
      after 6 months of therapy with nintedanib was assessed. RESULTS: Forty-one
      patients with a forced vital capacity (FVC) <=50% and/or a diffusing capacity of
      the lung for carbon monoxide (DLCO) <=35% predicted at the start of nintedanib
      treatment were enrolled. At the 6-month follow-up, the decline of DLCO (both
      absolute and % predicted) was significantly reduced compared to the pretreatment
      period (absolute DLCO at the -6-month, T0, and +6-month time points (5.48, 4.50,
      and 5.03 mmol/min/kPa, respectively, p = 0.03; DLCO% predicted was 32.73, 26.54,
      and 29.23%, respectively, p = 0.04). No significant beneficial effect was
      observed in the other functional parameters analyzed. The 1-year survival in this
      population was 79%, calculated from month 6 of therapy with nintedanib.
      CONCLUSIONS: This nationwide multicenter experience in patients with severe IPF
      shows that nintedanib slows down the rate of decline of absolute and % predicted
      DLCO but does not have significant impact on FVC or other lung parameters.

PMID- 29587264
TI  - Different Adaptive Responses to Hypoxia in Normal and Multiple Myeloma
      Endothelial Cells.
AB  - BACKGROUND/AIMS: Hypoxia is a powerful stimulator of angiogenesis under
      physiological as well as pathological conditions. Normal endothelial cells (EC),
      such as human umbilical vein EC (HUVEC), are relatively affected by hypoxic
      insult in terms of cell survival. In contrast, EC from tumors are particularly
      resistant to hypoxia-induced cell death. Previous reports have shown that EC in
      bone marrow from multiple myeloma (MM) patients had a hypoxic phenotype, even
      under normoxic conditions. The aim of this study was to evaluate whether HUVEC
      and MMEC adapt differently to hypoxia. METHODS: Cell proliferation was assessed
      by the CyQUANT assay. Cdc25A, p21, Bax, Bcl-xl, BNIP3, glucose transporter (GLUT)
      1, monocarboxylate transporter (MCT)-4 and carbonic anhydrase (CA)IX mRNA
      expression was determined by qRT-PCR. HIF-1alpha, BNIP3, Beclin-1, LC3B, livin,
      Bax, Bcl-xl, p21, p62 and beta-actin protein expression was analyzed by western
      blot. Apoptosis was determined by TUNEL assay. Silencing of BNIP3 was achieved by
      stealth RNA system technology. RESULTS: While HUVEC survival was reduced after
      prolonged hypoxic exposure, MMEC were completely unaffected. This difference was
      also significant in terms of livin, cdc25A and p21 expression. Hypoxia induced
      apoptosis and inhibited autophagy in HUVEC, but not in MMEC, where hypoxic
      treatment resulted in a more sustained adaptive response. In fact, MMEC showed a
      more significant increase in the expression of genes regulated transcriptionally
      by hypoxia-inducible factor (HIF)-1alpha. Interestingly, they showed higher
      expression of BNIP3 than did HUVEC, indicating a more pronounced autophagic (and
      pro-survival) phenotype. The potential role of BNIP3 in EC survival was confirmed
      by BNIP3 siRNA experiments in HUVEC, where BNIP3 inhibition resulted in reduced
      cell survival and increased apoptosis. CONCLUSION: These findings provide further
      information on how hypoxia may affect EC survival and could be important for a
      better understanding of EC physiology under normal and pathological conditions,
      such as in multiple myeloma.

PMID- 29587265
TI  - Transforming Growth Factor Beta 1 Drives a Switch in Connexin Mediated Cell-to
      Cell Communication in Tubular Cells of the Diabetic Kidney.
AB  - BACKGROUND/AIMS: Changes in cell-to-cell communication have been linked to
      several secondary complications of diabetes, but the mechanism by which connexins
      affect disease progression in the kidney is poorly understood. This study
      examines a role for glucose-evoked changes in the beta1 isoform of transforming
      growth factor (TGFbeta1), on connexin expression, gap-junction mediated
      intercellular communication (GJIC) and hemi-channel ATP release from tubular
      epithelial cells of the proximal renal nephron. METHODS: Biopsy material from
      patients with and without diabetic nephropathy was stained for connexin-26 (CX26)
      and connexin-43 (CX43). Changes in expression were corroborated by immunoblot
      analysis in human primary proximal tubule epithelial cells (hPTECs) and model
      epithelial cells from human renal proximal tubules (HK2) cultured in either low
      glucose (5mmol/L) +/- TGFbeta1 (2-10ng/ml) or high glucose (25mmol/L) for 48h or
      7days. Secretion of the cytokine was determined by ELISA. Paired whole cell patch
      clamp recordings were used to measure junctional conductance in control versus
      TGFbeta1 treated (10ng/ml) HK2 cells, with carboxyfluorescein uptake and ATP
      biosensing assessing hemi-channel function. A downstream role for ATP in
      mediating the effects of TGF-beta1 on connexin mediated cell communication was
      assessed by incubating cells with ATPgammaS (1-100uM) or TGF-beta1 +/- apyrase (5
      Units/ml). Implications of ATP release were measured through immunoblot analysis
      of interleukin 6 (IL-6) and fibronectin expression. RESULTS: Biopsy material from
      patients with diabetic nephropathy exhibited increased tubular expression of CX26
      and CX43 (P<0.01, n=10), data corroborated in HK2 and hPTEC cells cultured in
      TGFbeta1 (10ng/ml) for 7days (P<0.001, n=3). High glucose significantly increased
      TGFbeta1 secretion from tubular epithelial cells (P<0.001, n=3). The cytokine
      (10ng/ml) reduced junctional conductance between HK2 cells from 4.5+/-1.3nS in
      control to 1.15+/-0.9nS following 48h TGFbeta1 and to 0.42+/-0.2nS after 7days
      TGFbeta1 incubation (P<0.05, n=5). Acute (48h) and chronic (7day) challenge with
      TGFbeta1 produced a carbenoxolone (200uM)-sensitive increase in
      carboxyfluorescein loading, matched by an increase in ATP release from 0.29+/
      0.06MUM in control to 1.99+/-0.47MUM after 48hr incubation with TGFbeta1
      (10ng/ml; P<0.05, n=3). TGF-beta1 (2-10ng/ml) and ATPgammas (1-100uM) increased
      expression of IL-6 (P<0.001 n=3) and fibronectin (P<0.01 n=3). The effect of TGF
      beta1 on IL-6 and fibronectin expression was partially blunted when preincubated
      with apyrase (n=3). CONCLUSION: These data suggest that chronic exposure to
      glucose-evoked TGFbeta1 induce an increase in CX26 and CX43 expression,
      consistent with changes observed in tubular epithelia from patients with diabetic
      nephropathy. Despite increased connexin expression, direct GJIC communication
      decreases, whilst hemichannel expression/function and paracrine release of ATP
      increases, changes that trigger increased levels of expression of interleukin 6
      and fibronectin. Linked to inflammation and fibrosis, local increases in
      purinergic signals may exacerbate disease progression and highlight connexin
      mediated cell communication as a future therapeutic target for diabetic
      nephropathy.

PMID- 29587266
TI  - Overexpression of PTPN2 in Visceral Adipose Tissue Ameliorated Atherosclerosis
      via T Cells Polarization Shift in Diabetic Apoe-/- Mice.
AB  - BACKGROUND/AIMS: Dysregulated inflammation in adipose tissue, marked by increased
      pro-inflammatory T-cell accumulation and reduced regulatory T cells (Treg),
      contributes to diabetes-associated insulin resistance and atherosclerosis.
      However, the molecular mechanisms underlying T-cell-mediated inflammation in
      adipose tissue remain largely unknown. METHODS: Sixty apolipoprotein E (ApoE-/-)
      mice were randomly divided into chow and diabetes groups. Diabetes was induced by
      a high-fat and high-sugar diet combined with low-dose streptozotocin. Then we
      transferred a recombinant adenovirus carrying the protein tyrosine phosphatase
      non-receptor type 2 (PTPN2) gene into epididymal white adipose tissue (EWAT) of
      ApoE-/- mice. After transfection, all mice were euthanized to evaluate the
      effects of PTPN2 on T cells polarization and atherosclerosis. RESULTS: PTPN2 was
      downregulated in EWAT of diabetic ApoE-/- mice. PTPN2 overexpression in EWAT
      reversed the high Th1/Treg and Th17/Treg ratios in EWAT of diabetic mice. In
      addition, PTPN2 overexpression in EWAT could significantly reduce macrophages
      infiltration, the ratio of M1/M2 macrophages and the expression of pro
      inflammatory cytokines in EWAT, improving insulin resistance. In aortic root
      lesions, the vulnerability index were significantly decreased by overexpression
      of PTPN2 in EWAT. CONCLUSION: These data suggested that PTPN2 overexpression in
      EWAT would inhibit systemic inflammation and increase the plaque stability via T
      cells polarization shift in diabetic mice.

PMID- 29587267
TI  - Distance from Home to Research Center: A Barrier to In-Person Visits but Not
      Treatment Adherence in a Stroke Trial.
AB  - BACKGROUND AND PURPOSE: Clinical trials often seek to enroll patients from both
      urban and rural areas to safeguard the generalizability of results. However,
      maintaining contact with patients who live away from a recruitment site,
      including rural areas, can be challenging. In this research we examine the effect
      of distance between patient and study centers on treatment adherence and
      retention. METHODS: Secondary analysis of 2,466 participants in the Insulin
      Resistance Intervention after Stroke trial who were enrolled from research sites
      in the United States. Driving distance between the zipcodes of patient's reported
      place of residence and the study center was calculated. Outcome measures were
      loss to follow-up, completion of annual in-person visits, adherence to preventive
      therapy, and adherence to study drug in the first 3 years of participation.
      Logistic regression models were used to adjust for confounders. RESULTS: Distance
      from residence to research center was not associated with loss to follow-up,
      adherence to study drug, or adherence to preventive therapy (p > 0.05 for each).
      However, patients who lived farther from the research center (>120 miles),
      compared to patients who lived closer (<60 miles), were less likely to complete
      the second annual in-person visit (62 vs. 81%; adjusted OR 0.48; 95% CI 0.31
      0.75) and third visit (53 vs. 75%; adjusted OR 0.44; 95% CI 0.29-0.67).
      CONCLUSIONS: Distance between patient and study center was an independent
      predictor of missed in-person visits but not with adherence to study treatment or
      preventive care.

PMID- 29587268
TI  - MicroRNA-30a Suppresses the Activation of Hepatic Stellate Cells by Inhibiting
      Epithelial-to-Mesenchymal Transition.
AB  - BACKGROUND/AIMS: The activation of hepatic stellate cells (HSCs) is considered as
      a pivotal event in liver fibrosis and epithelial-mesenchymal transition (EMT)
      process has been reported to be involved in HSC activation. It is known that
      microRNAs (miRNAs) play a pro-fibrotic or anti-fibrotic role in HSC activation.
      Recently, emerging studies show that miR-30a is down-regulated in human cancers
      and over-expression of miR-30a inhibits tumor growth and invasion via suppressing
      EMT process. However, whether miR-30a could regulate EMT process in HSC
      activation is still unclear. METHODS: miR-30a expression was quantified using
      real-time PCR in carbon tetrachloride (CCl4)-induced rat liver fibrosis,
      activated HSCs and patients with cirrhosis. Roles of miR-30a in liver fibrosis in
      vivo and in vitro were also analyzed. Luciferase activity assays were performed
      to examine the binding of miR-30a to the 3'-untranslated region of snail family
      transcriptional repressor 1 (Snai1). RESULTS: miR-30a was down-regulated in human
      cirrhotic tissues. In CCl4 rats, reduced miR-30a was found in fibrotic liver
      tissues as well as isolated HSCs. There was a significant reduction in miR-30a in
      primary HSCs during culture days. miR-30a over-expression resulted in the
      suppression of CCl4-induced liver fibrosis. Restoration of miR-30a led to the
      inhibition of HSC activation including cell proliferation, alpha-SMA and collagen
      expression. Notably, miR-30a inhibited EMT process, with a reduction in TGF-beta1
      and Vimentin as well as an increase in GFAP and E-cadherin. miR-30a induced a
      significant reduction in Snai1 protein expression when compared with the control.
      Interestingly, Snail protein expression was increased during liver fibrosis,
      indicating that there may be a negative correlation between miR-30a level and
      Snai1 protein expression. Further studies demonstrated that Snai1 was a target of
      miR-30a. CONCLUSION: Our results suggest that miR-30a inhibits EMT process, at
      least in part, via reduction of Snai1, leading to the suppression of HSC
      activation in liver fibrosis.

PMID- 29587270
TI  - Atrial Fibrillation, Past and Future: From a Stroke Non-Entity to an Over
      Targeted Cause.

PMID- 29587269
TI  - Functions of the Signal Transducer and Activator of Transcription 6 in a
      Behavioral Animal Model of Depression.
AB  - AIMS: Depression is one of the most common inflammatory and mental disorders.
      Signal transducer and activator of transcription 6 (STAT6) plays a crucial role
      in the pathology of mental disorders as well as inflammatory diseases. METHODS:
      Here we determined the role of STAT6 in the pathogenesis of depression using
      STAT6-deficient mice in a forced swimming test. RESULTS: The immobility time was
      significantly decreased in STAT6-deficient mice compared to wild-type mice
      without alteration of locomotor activity. STAT6-deficient mice exhibited a
      significantly enhancing dopamine and 5-hydroxytryptamine (5-HT, serotonin) in
      brain. In addition, the expression of serotonin transporter in the hippocampus
      was markedly downregulated in STAT6-deficient mice. These results provide the
      first evidence that STAT6 affects depressive-like behavior through downregulating
      monoamines, including dopamine and 5-HT in the hippocampus of brain. CONCLUSIONS:
      In conclusion, identification of STAT6 signaling pathways on depression might
      open new perspectives for antidepressant therapies.

PMID- 29587271
TI  - Iterative Variance Stabilizing Transformation Denoising of Spectral Domain
      Optical Coherence Tomography Images Applied to Retinoblastoma.
AB  - BACKGROUND: Due to the presence of speckle Poisson noise, the interpretation of
      spectral domain-optical coherence tomography (SD-OCT) images frequently requires
      the use of data averaging to improve the signal-to-noise ratio. This implies long
      acquisition times and requires patient sedation in some cases. Iterative variance
      stabilizing transformation (VST) is a possible approach by which to remove
      speckle Poisson noise on single images. METHODS: We used SD-OCT images of human
      and murine (LH Beta-Tag mouse model) retinas with and without retinoblastoma
      acquired with 2 different imaging devices (Bioptigen and Micron IV). These images
      were processed using a denoising workflow implemented in Matlab. RESULTS: We
      demonstrated the presence of speckle Poisson noise, which can be removed by a VST
      based approach. This approach is robust as it works in all used imaging devices
      and in both human and mouse retinas, independently of the tumor status. The
      implemented algorithm is freely available from the authors on demand.
      CONCLUSIONS: On a single denoised image, the proposed method provides results
      similar to those expected from the SD-OCT averaging. Because of the friendly user
      interface, it can be easily used by clinicians and researchers in ophthalmology.

PMID- 29587272
TI  - Development of an Immunoassay for Detection of Torque Teno Virus (TTV) Antibodies
      Using the N22 Expression Product from TTV Genotype 2.
AB  - AIMS: This study describes an immunoassay to detect anti-torque teno virus (TTV)
      antibodies using a peptide obtained from expression of the N22 region of TTV
      genotype 2. METHODS: The N22 region (~500 bp) of TTV genotype 2 was cloned in a
      pET-28a(+) vector and expressed in ZYM-5052 autoinduction medium. Following metal
      affinity chromatography, a purified polypeptide was used as an antigen for the
      development of an immunoassay to detect anti-TTV antibodies in human sera.
      RESULTS: Recombinant protein (~25-kDa) was obtained after 24 h of incubation at
      25 degrees C in ZYM-5052 autoinduction medium. A blot assay developed using this
      polypeptide as an antigen and TTV-positive sera as the primary antibody produced
      a distinct spot on the nitrocellulose membrane. Serum samples from 36 of 42
      patients with renal disease and 29 of 48 patients with liver diseases produced a
      positive signal using this immunoassay. Simultaneously, 18 of 48 healthy controls
      were also detected to be positive for anti-TTV antibodies. These results were
      found to be comparable with TTV detection using PCR, and the assay showed a high
      sensitivity and specificity (i.e., 97.44 and 91.67%, respectively). Moreover,
      this assay could detect TTV infection irrespectively of the genotype, including
      cases of mixed infection. CONCLUSION: The present immunoassay using the N22
      expression product may be used as an alternative to PCR to detect TTV infection
      in large populations.

PMID- 29587273
TI  - Neutrophil-to-Lymphocyte Ratio and Platelet Count Predict Long-Term Outcome of
      Stage IIIC Epithelial Ovarian Cancer.
AB  - BACKGROUND/AIMS: Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and
      platelet count (PC) in patients with International Federation of Gynecology and
      Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) is controversial.
      METHODS: A total of 370 stage IIIC EOC patients who underwent primary debulking
      surgery (PDS) at the Department of Gynecology of Liaoning Cancer Hospital and
      Institute between January 2003 and August 2016 and had full information were
      involved. Patients were stratified into a high NLR (H-NLR) group versus a low NLR
      (L-NLR) group and a high PC (H-PC) group versus a low PC (L-PC) group according
      to cutoff values calculated through receiver operating characteristic (ROC)
      curves. Prognostic values of NLR and PC for progression-free survival (PFS) and
      overall survival (OS) were assessed. RESULTS: We identified the optimal cut-off
      value of 3.08 for NLR and 289.5*109/L for PC. The median PFS and OS of the
      patients with H-NLR were shorter than L-NLR (PFS: 16.9 months vs. 19.5 months,
      hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.03-1.63, P = 0.022; OS:
      33.5 months vs. 46.8 months, HR 1.3, 95% CI 1.01-1.66, P = 0.001). The median PFS
      and OS of the patients with H-PC were shorter than L-PC (PFS: 15.3 months vs.
      21.6 months, HR 1.3, 95% CI 1.04-1.63, P < 0.001; OS: 37.3 months vs. 46.1
      months, HR 1.14, 95% CI 0.89-1.46, P = 0.306). CONCLUSIONS: H-NLR and H-PC could
      predict poor long-term outcome of patients with FIGO stage III EOC.

PMID- 29587274
TI  - Bajijiasu Ameliorates beta-Amyloid-Triggered Endoplasmic Reticulum Stress and
      Related Pathologies in an Alzheimer's Disease Model.
AB  - BACKGROUND/AIMS: Alzheimer disease (AD) is a common neurodegenerative disease
      that is characterized by the deposition of beta-amyloid peptide and formation of
      intracellular neurofibrillary tangles. Due to the failure of various clinical
      trials of novel drugs for AD, effective drugs for AD treatment are urgently
      required. METHODS: In this study, we used the classic APP/PS1 mouse model to
      explore the neuroprotective effects of a new compound, bajijiasu, and the
      mechanisms involved. Behavioral tests and western blotting were performed to
      assess the beneficial effects of bajijiasu in APP/PS1 mice. RESULTS: Morris water
      maze and Y-maze test results showed that oral administration of bajijiasu (35
      mg/kg/day and 70 mg/kg/day) improved learning and memory abilities in APP/PS1
      mice. Bajijiasu reduced ROS and MDA levels in both the hippocampus and cortex.
      Moreover, western blotting results showed that bajijiasu protected neurons from
      apoptosis, elevated the expression levels of neurotrophic factors, and alleviated
      endoplasmic reticulum stress in both the hippocampus and cortex. CONCLUSION:
      These results indicate that the mechanisms underlying the effects of bajijiasu on
      AD might be related to beta-amyloid-downstream pathologies, particularly
      endoplasmic reticulum stress.

PMID- 29587275
TI  - Efficacy Analysis of Capsaicin 8% Patch in Neuropathic Peripheral Pain Treatment.
AB  - BACKGROUND/AIMS: Several guidelines for neuropathic pain management and various
      effective drugs are available; however, neuropathic pain remains undertreated.
      This retrospective study aimed to evaluate the efficacy of topical capsaicin 8%
      in peripheral neuropathic pain in a routine clinical setting. METHODS:
      Therapeutic efficacy was evaluated through pain intensity, using numerical pain
      rating scale at baseline and 7-14 days after each treatment, and using pain
      treatment area (PTA) assessed immediately before each treatment. RESULTS: A total
      of 43 patients with either post-herpetic neuralgia or post-traumatic/post
      surgical neuropathic pain were enrolled. The median percentage reduction in
      numerical pain rating scale score and in PTA was -40.0 (-50.0 to -33.3; 95% CI,
      bootstrap) and -35.1 (-50.9 to 3.4; 95% CI, bootstrap), respectively. Pain
      intensity and PTA were equally improved and reduced in both treated conditions.
      CONCLUSION: This study suggests that topical capsaicin 8% reduces peripheral
      neuropathic pain as well as treatment pain area.

PMID- 29587276
TI  - Improving Bone Regeneration Using Chordin siRNA Delivered by pH-Responsive and
      Non-Toxic Polyspermine Imidazole-4,5-Imine.
AB  - BACKGROUND/AIMS: Bone nonunion remains a challenge for orthopaedists. The
      technological advancements that have been made in precisely silencing target
      genes have provided promising methods to address this challenge. METHODS: We
      detected the expression levels of the bone morphogenetic protein (BMP) inhibitors
      Chordin, Gremlin and Noggin using realtime PCR in bone mesenchymal stem cells
      (BMSCs) isolated from patients with normal fracture healing and those with bone
      nonunion. Moreover, we detected the expression of Chordin, Gremlin and Noggin
      during the osteogenic differentiation of human BMSCs (hBMSCs) using real-time PCR
      and Western blot. We delivered Chordin siRNA to hBMSCs using a previously
      reported cationic polymer, polyspermine imidazole-4,5-imine (PSI), as a pH
      responsive and non-cytotoxic transfection agent. The apoptosis and cellular
      uptake efficiency were analysed by flow cytometry. RESULTS: We identified Chordin
      as the most appropriate potential therapeutic target gene for enhancing the
      osteogenic differentiation of hBMSCs. Chordin knockdown rescued the osteogenic
      capacity of hBMSCs isolated from patients with bone nonunion. Highly efficient
      knockdown of Chordin was achieved in hBMSCs using PSI. Chordin knockdown promoted
      hBMSC osteogenesis and bone regeneration in vitro and in vivo. CONCLUSIONS: Our
      results suggest that Chordin is a potential target for improving osteogenesis and
      bone nonunion therapy and that responsive and non-toxic cationic polyimines such
      as PSI are therapeutically feasible carriers for the packaging and delivery of
      Chordin siRNA to hBMSCs.

PMID- 29587277
TI  - Mitofusin-2 Triggers Cervical Carcinoma Cell Hela Apoptosis via Mitochondrial
      Pathway in Mouse Model.
AB  - BACKGROUND/AIMS: Cervical carcinoma continues to be one of the most dangerous
      cancer types, and more effective therapies are urgently needed for cervical
      carcinoma treatment. Mitochondria-associated Mitofusin 2 has influence on the
      progression of many cancers. In the current study, we aimed to focus on the cell
      apoptotic effects of Mfn2 on cervical carcinoma HeLa cells in vitro and to try to
      explore its underlying mechanisms. Moreover, we investigated the anticancer
      potential of Mfn2 in a cervical carcinoma mouse model. METHODS: Adenovirus-Mfn2
      (Adv-Mfn2) was used to deliver mfn2 into HeLa cells and tumour tissues in a nude
      mouse model. CCK-8, TUNEL assay, Western blot and immunohistochemical staining
      were performed to detect the effects of Mfn2. The mRNA level of Mfn2 was
      determined by quantitative realtime PCR (qRT-PCR) analysis. The effect of Mfn2 on
      cell apoptosis was investigated by flow cytometry. Flow cytometry was used to
      assess the change of the mitochondrial membrane potential of the cells treated
      with JC-1 assay. Mfn2, Bax, Bcl-2, cytochrome c, cleaved caspase-3, and cleaved
      caspase-9 protein levels were analysed by Western blot. RESULTS: Data from CCK-8
      and flow cytometry showed that Mfn2 could inhibit proliferation and induce
      apoptosis in a dose- and time-dependent manner in HeLa cells. JC-1 test results
      revealed that the membrane potential of the mitochondrial decreased in a dose
      dependent manner in HeLa cells after Adv-Mfn2 treatment. The data from Western
      blot confirmed that higher cytosolic amounts of cytochrome c with increasing
      doses of Adv-Mfn2 signified the onset of the intrinsic apoptotic pathway. Levels
      of cleaved caspase-3 and cleaved caspase-9 increased in HeLa cells with Adv-Mfn2
      treatment. We also found significant increases in the Bax level and a decreased
      Bcl-2 level with Adv-Mfn2 treatment. We further confirmed that Mfn2 could
      significantly inhibit the growth of the cervical tumour in the xenografted
      cervical carcinoma mouse model. After a 9-day-treatment, the tumours of the Adv
      mfn2 group were inhibited and induced into apoptosis. The results demonstrated
      that the overexpression of Mfn2 could not only increase the levels of Bax and Bid
      in cervical tumour cells but also decrease the phosphorylation of Bad and the
      expression of Bcl-2. CONCLUSION: These studies suggested that the overexpression
      of Mfn2 could trigger cervical tumour apoptosis in vitro and in vivo, which was
      related to the mitochondrial pathway, and may provide a new treatment target for
      cervical carcinoma.

PMID- 29587278
TI  - A Risk-Adapted Approach to Patients with Stage I Seminoma according to the Status
      of Rete Testis: The Fourth Spanish Germ Cell Cancer Group Study.
AB  - OBJECTIVE: The aim of this study was to assess a risk-adapted strategy for stage
      I seminoma guided by the presence of rete testis invasion. METHODS: Between
      January 2013 and December 2015, a total of 135 consecutive patients with stage I
      seminoma from 18 Spanish tertiary hospitals were included in a prospective
      multicenter study. Median patient age was 38 years (range 22-60). Preoperative
      beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis
      invasion was present in 47.4% of patients. After orchiectomy, subjects with rete
      testis invasion were treated with 2 courses of adjuvant carboplatin (area under
      the curve of 7, with 21-day interval). Those without this risk factor were
      managed by surveillance. Disease-free survival (DFS) and overall survival (OS)
      were estimated with the Kaplan-Meier method. RESULTS: After a median follow-up
      time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after
      carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135
      patients are currently disease free without sequelae. Three-year DFS was 92.0 and
      98.2% for patients on surveillance and after carboplatin, respectively. Three
      year OS was 100%. CONCLUSION: A risk-adapted approach based on rete testis
      invasion as a single risk factor is feasible and yielded an excellent outcome
      with a 3-year DFS of 94.9%.

PMID- 29587279
TI  - Intraoperative Analgesic Regimen and Cholecystectomy: A Closer Look.

PMID- 29587280
TI  - Inhibition of Cgkii Suppresses Seizure Activity and Hippocampal Excitation by
      Regulating the Postsynaptic Delivery of Glua1.
AB  - BACKGROUND/AIMS: The imbalance between excitation and inhibition is a defining
      feature of epilepsy. GluA1 is an AMPA receptor subunit that can strengthen
      excitatory synaptic transmission when upregulated in the postsynaptic membrane,
      which has been implicated in the pathogenesis of epilepsy. cGKII, a cGMP
      dependent protein kinase, regulates the GluA1 levels at the plasma membrane.
      METHODS: To explore the role of cGKII in epilepsy, we investigated the expression
      of cGKII in patients with temporal lobe epilepsy (TLE) and in a pilocarpine
      induced rat model and then performed behavioral, histological, and
      electrophysiological analyses by applying either a cGKII agonist or inhibitor in
      the hippocampus of the animal model. RESULTS: cGKII expression was upregulated in
      the epileptogenic brain tissues of both humans and rats. Pharmacological
      activation or inhibition of cGKII induced changes in epileptic behaviors in vivo
      and epileptic discharges in vitro. Further studies indicated that cGKII
      activation disrupted the balance of excitation and inhibition due to strengthened
      AMPAR-mediated excitatory synaptic transmission. Moreover, cGKII regulated
      epileptic seizures by phosphorylating GluA1 at Ser845 to modulate the expression
      and function of GluA1 in the postsynaptic membrane. CONCLUSION: These results
      suggest that cGKII plays a key role in seizure activity and could be a potential
      therapeutic target for epilepsy.

PMID- 29587282
TI  - Can a Non-Native Primate Be a Potential Seed Disperser? A Case Study on Saimiri
      sciureus in Pernambuco State, Brazil.
AB  - The interaction between native fleshy-fruit plants and introduced fruit consumers
      contributes to the dynamics of highly fragmented environments. Such interactions
      can occur through pollination and seed dispersal. Here, we investigated the
      potential of seed dispersing by a non-native primate, the squirrel monkey
      (Saimiri sciureus), in an urban Atlantic forest fragment in north-eastern Brazil.
      Fleshy fruits from non-native plants were preferentially exploited by the
      squirrel monkeys. We measured 147 seeds (width and length) from 20 of 106 faecal
      samples. The dispersed seeds were from five plant species (four families). We
      found a positive correlation between the size of seeds found in faecal samples
      with their availability in the habitat. Only one seed was found visually damaged
      after passage through the squirrel monkeys' guts. The defecated seeds were
      uniformly distributed (variance to mean ratio index) in the home range of
      squirrel monkeys, and there was a lack of specific latrines (i.e., habitat
      preference for defecation). Our data provide evidence that non-native S. sciureus
      may in be (i) acting as a potential seed disperser of native plants in the
      Atlantic forest fragment, (ii) contributing to the ecological role of native
      frugivores, and (iii) potentially contributing to the regeneration process of the
      highly degraded study site.

PMID- 29587281
TI  - MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by
      Down-Regulating MTA1.
AB  - BACKGROUNDS/AIMS: MicroRNAs (miRs) often contribute to the progression of non
      small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung
      homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the
      proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of
      human NSCLC cells via targeting MTA1. METHODS: NSCLC and adjacent normal tissues
      were collected from 194 patients with NSCLC. Positive expression of MTA1 protein
      was detected by immunohistochemistry. The highest levels of expression of miR-183
      were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to
      the following groups: blank, negative control (NC), miR-183 mimic, miR-183
      inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR
      183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail,
      PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR
      and western blot analysis. Cell proliferation, apoptosis, migration and invasion
      were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays.
      Tumor xenografts were conducted in nude mice to determine tumor growth. RESULTS:
      SPC-A-1 cells with the highest levels of miR-183 expression were selected.
      Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and
      protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while
      mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were
      increased. MiR-183 was over-expressed in the miR-183 mimic group and under
      expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In
      the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E
      cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression
      levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell
      proliferation, migration, invasion and tumor growth were reduced relative to the
      blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend.
      CONCLUSION: Our study indicates that miR-183 down-regulates MTA1 to inhibit the
      proliferation, EMT, migration and invasion of human NSCLC cells.

PMID- 29587283
TI  - Old and New Gut Hormone, Gastrin and Acid Suppressive Therapy.
AB  - Gastrin acts physiologically as a gut hormone to stimulate acid secretion after
      meal and as a cell-growth factor of oxyntic mucosa. Increase in serum gastrin
      level happens under various conditions including Zollinger-Ellison syndrome,
      antral G cell hyperplasia, autoimmune gastritis, atrophic gastritis, renal
      failure, vagotomy, Helicobacter pylori infection and acid suppressive therapy. As
      acid suppressive therapy causes hypergastrinemia, the association between acid
      suppressive therapy and gastric neuroendocrine cell tumor (NET) has been
      discussed during the past 30 years. In this review article, the definition of
      hypergastrinemia and the related disorders including acid suppressive therapy and
      gastric NET are discussed.

PMID- 29587285
TI  - Tumor Angiogenesis: A Key Target for Cancer Therapy.

PMID- 29587284
TI  - Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow
      Stromal Cells in a Rodent Ischemic Stroke Model.
AB  - BACKGROUND/AIMS: Bone marrow stromal cells (BMSCs) transplantation is an
      important strategy for the treatment of ischemic stroke. Currently, there are no
      effective methods to guide BMSCs toward the targeted site. In this study, we
      investigated the effect of electrical stimulation on BMSCs migration in an
      ischemic model of rats. METHODS: Adult male Wistar rats weighing 200 to 250 g
      received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs
      (2.5*105 cells/ 4 ul PBS) were stereotaxically injected into the left corpus
      callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a
      diameter of 3 mm connected to an implantable electrical stimulator was placed on
      the right frontal epidural space and a counter electrode was placed in the extra
      cranial space. Electrical stimulation at preset current (100 uA) and frequency
      (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8,
      and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and
      cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of
      infarction area and the migration distance and area of BMSCs found in the brain
      tissue. After evaluating cell migration, we proceeded to explore the mechanisms
      guiding these observations. MCAO rats without BMSCs transplantation were
      stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats
      were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1alpha)
      level of brain tissues in the bilateral cortex and striatum. RESULTS: Behavioral
      tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed
      significant amelioration in mNSS and cylinder test compared to control group
      (p<0.05). Similarly, the infarction areas of stroke rats in stimulation group
      were significantly decreased compared to control group (p<0.05). Migration
      distance and area of transplanted BMSCs were significantly longer and wider
      respectively in stimulation group. An increased concentration gradient of SDF
      1alpha in stimulation group accompanied this enhanced migration of transplanted
      cells. CONCLUSIONS: These results suggest that electrical stimulation enhances
      migratory ability of transplanted BMSCs in ischemic stroke model of rats. If we
      can direct the implanted BMSCs to the site of interest, it may lead to a greater
      therapeutic effect.

PMID- 29587286
TI  - Chromosome Banding in Amphibia. XXXVII. Y-Autosome Translocations in Anura.
AB  - A detailed cytogenetic study on anurans belonging to the unranked taxon
      Terraranae revealed the existence of microscopically recognizable XY?/XX? or
      ZZ?/ZW? sex chromosomes in 11 species. Furthermore, in some species Y-autosome
      translocations were found, of which 5 could be confirmed. The male individuals
      carrying the Y-autosome translocations still coexist with the males showing the
      original karyotypes. The present report gives an overview on the mitotic and
      meiotic structure, staining and banding properties, functional importance, and
      similarities and differences of these Y-autosome translocations which are very
      rare in vertebrates. A mathematical model was constructed that calculates the
      various probabilities of further chromosome rearrangements in these karyotypes
      with Y-autosome translocations. The localization of the differential segment
      containing the hypothetical male sex-determining gene in the Y chromosome is
      discussed.

PMID- 29587287
TI  - Cohesin RAD21 Gene Promoter Methylation in Patients with Chronic Lymphocytic
      Leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults
      and is characterized by the presence of specific cytogenetic abnormalities. CLL
      research has been focused on epigenetic processes like gene promoter methylation
      of CpG islands. In the present study, the methylation status of the RAD21 gene is
      studied and associated with cytogenetic findings in CLL patients in order to
      investigate its possible implication in CLL pathogenesis and the formation of CLL
      chromosomal abnormalities.

PMID- 29587288
TI  - Effect of Sodium Thiosulfate on Arterial Stiffness in End-Stage Renal Disease
      Patients Undergoing Chronic Hemodialysis (Sodium Thiosulfate-Hemodialysis Study):
      A Randomized Controlled Trial.
AB  - BACKGROUND: Arterial stiffness (AS) and vascular calcification are significantly
      related to a high cardiovascular mortality risk in hemodialysis (HD) patients.
      Intravenous sodium thiosulfate (IV STS) can prevent and delay the vascular
      calcification progression in uremic states; however, the STS effect on AS has not
      been assessed. This study aimed to evaluate the STS efficacy on vascular
      calcification and AS in HD patients. METHODS: Fifty HD patients with abnormal AS,
      as measured via the cardio-ankle vascular index (CAVI >=8), were prospectively
      randomized to open-label 12.5 g IV STS during the last HD hour twice weekly for 6
      months (n = 24) or the usual care (control group; n = 26). Patients and treating
      physicians were not blinded. The CAVI, coronary artery calcification (CAC) score,
      hemodynamics, and biochemical parameters were measured at the baseline and at 3
      and 6 months. RESULTS: All the baseline parameters were comparable. The IV STS
      significantly reduced the CAVI when compared to the control group (mean CAVI
      difference = -0.53; 95% CI -1.00 to -0.06; p = 0.03). A significant CAVI
      improvement was seen in those patients without diabetes mellitus. The natural
      logarithm of the CAC volume score was significantly increased in the control
      group. The high sensitivity C-reactive protein level was slightly lowered in the
      IV STS group (not significant). CONCLUSION: The intradialytic STS treatment
      significantly reduced the AS, as measured by the CAVI, and stabilized the
      vascular calcification in the HD patients. STS may be a novel therapeutic
      strategy for delaying and treating the structural and functional vascular wall
      abnormalities in HD patients.

PMID- 29587289
TI  - Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in
      Aged Mice.
AB  - BACKGROUND: Fisetin is commonly used as an anti-inflammatory and neuroprotective
      drug. In this study, we aimed to investigate the efficacy of fisetin in
      alleviating intracerebral hemorrhage (ICH)-induced brain injury. METHODS: Mouse
      ICH models were constructed using the collagenase-induction method. ICH mice
      received fisetin treatment at the dose of 10-90 mg/kg, followed by the evaluation
      of neurological deficit through neurologic severity scores (mNSS), brain water
      content and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis
      of cell apoptosis. Cytokine levels were also assessed with enzyme-linked
      immunosorbent assay. The activation of astrocytes and microglia was evaluated
      through S100 staining and Western blot analysis of ionized calcium-binding
      adaptor molecule 1 respectively. Nuclear factor kappa-B (NF-kappaB) signaling was
      also evaluated by Western blot. RESULTS: ICH mice demonstrated dramatic increase
      in mNSS, brain edema and cell apoptosis, indicating severe brain deficit. Fisetin
      treatment lowered these parameters, suggesting the alleviation of brain injury.
      Levels of proinflammatory cytokines were reduced, accompanied by a prominent
      decrease in activated astrocytes and microglia. NF-kappaB signaling was also
      attenuated by fisetin treatment. CONCLUSION: Fisetin effectively alleviates ICH
      by downregulating proinflammatory cytokines and attenuating NF-kappaB signaling.
      These data suggest fisetin as a valuable natural flavonol for clinical management
      of ICH-induced brain injury.

PMID- 29587290
TI  - Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the
      Literature.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma is one of the most lethal types of
      cancer with a 5-year survival rate of around 7%. Due to the relatively poor
      prognosis, the potential need of an effective chemoprevention is highly needed.
      SUMMARY: Different risk factors like smoking or hereditary tumour syndromes
      should be known for early detection of pancreatic intraepithelial neoplasia.
      Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas
      potential chemopreventive drugs compromise aspirin, metformin or statins. This
      review aims to give an overview on potential risk factors for the development of
      pancreatic cancer. Furthermore, we try to summarise known chemopreventive agents
      to support the fight against this lethal disease. Key Messages: On the one hand,
      there are natural agents that exhibit preventive properties and can lead to the
      prohibition of pancreatic cancer. On the other hand, there are drugs and agents
      that are currently used in other contexts and are thus already approved and
      studied in terms of their mechanisms of effects and the related secondary
      effects.

PMID- 29587291
TI  - Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal
      Muscle Cells and Impacts Irisin In Vivo.
AB  - BACKGROUND/AIMS: All-trans retinoic acid (ATRA) has protective effects against
      obesity and metabolic syndrome. We here aimed to gain further insight into the
      interaction of ATRA with skeletal muscle metabolism and secretory activity as
      important players in metabolic health. METHODS: Cultured murine C2C12 myocytes
      were used to study direct effects of ATRA on cellular fatty acid oxidation (FAO)
      rate (using radioactively-labelled palmitate), glucose uptake (using
      radioactively-labelled 2-deoxy-D-glucose), triacylglycerol levels (by an
      enzymatic method), and the expression of genes related to FAO and glucose
      utilization (by RT-real time PCR). We also studied selected myokine production
      (using ELISA and immunohistochemistry) in ATRA-treated myocytes and intact mice.
      RESULTS: Exposure of C2C12 myocytes to ATRA led to increased fatty acid
      consumption and decreased cellular triacylglycerol levels without affecting
      glucose uptake, and induced the expression of the myokine irisin at the mRNA and
      secreted protein level in a dose-response manner. ATRA stimulatory effects on FAO
      related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of
      peroxisome proliferator-activated receptor beta/delta and retinoid X receptors,
      but not of retinoic acid receptors, and were partially blocked by an AMP
      dependent protein kinase inhibitor. Circulating irisin levels were increased by 5
      fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and
      adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of
      FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from
      skeletal muscle and the liver and its accumulation in interscapular brown and
      inguinal white adipose depots. CONCLUSION: These results provide new mechanistic
      insights on how ATRA globally stimulates FAO and enhances irisin secretion,
      thereby contributing to leaning effects and improved metabolic status.

PMID- 29587293
TI  - Effects of MiR-375-BMPR2 as a Key Factor Downstream of BMP15/GDF9 on the
      Smad1/5/8 and Smad2/3 Signaling Pathways.
AB  - BACKGROUND/AIMS: Bone morphogenetic protein 15 (BMP15) and growth differentiation
      factor 9 (GDF9), which are secreted by oocytes, are important regulators of
      follicular growth and development and ovarian function. These two factors can
      regulate the proliferation and apoptosis of cumulus cells via modulation of the
      Smad signaling pathway. Studies have shown that BMP15 and GDF9 can affect the
      level of miR-375, whereas the target gene of miR-375 is BMPR2, the type II
      receptor of BMP15 and GDF9. However, whether or how the BMP15/ GDF9-miR-375-BMPR2
      pathway affects the proliferation and apoptosis of bovine cumulus cells through
      regulation of the Smad signaling pathway remains unclear. METHODS: In this study,
      cumulus cells were first obtained from cumulus-oocyte complexes (COCs).
      Appropriate concentrations of BMP15 and GDF9 were added during the in vitro
      culture process. Cell Counting Kit-8 (CCK-8) analyses and flow cytometry were
      used to determine the effects of BMP15/GDF9 on bovine cumulus cells proliferation
      and apoptosis. Subsequently, miR-375 mimics, miR-375 inhibitor and BMPR2 siRNA
      were synthesized and used for transfection experiments. Western Blot analysis was
      used to detect changes before and after transfection in the expression levels of
      the BMP15/GDF9 type I receptors ALK4, ALK5 and ALK6; the phosphorylation levels
      of Smad2/3 and Smad1/5/8, which are key signaling pathway proteins downstream of
      BMP15/GDF9; the expression levels of PTX3, HAS2 and PTGS2, which are key genes
      involved in cumulus cells proliferation; and Bcl2/Bax, which are genes involved
      in apoptosis. RESULTS: The addition of 100 ng/mL BMP15 or 200 ng/mL GDF9 or the
      combined addition of 50 ng/mL BMP15 and 100 ng/mL GDF9 effectively inhibited
      bovine cumulus cell apoptosis and promoted cell proliferation. BMP15/GDF9
      negatively regulated miR-375 expression and positively regulated BMPR2
      expression. High levels of miR-375 and inhibition of BMPR2 resulted in increased
      expression of ALK4 and decreased expression of PTX3, HAS2 and PTGS2, whereas miR
      375 inhibition resulted in the opposite results. BMP15 and GDF9 significantly
      activated the levels of p-Smad2/3 and p-Smad1/5/8, whereas miR-375 inhibited the
      levels of p-Smad2/3 and p-Smad1/5/8 by negatively regulating BMPR2 and also led
      to apoptosis. CONCLUSION: BMP15 and GDF9 have synergistic effects and can act
      through miR-375 to affect the expression levels of type I receptor ALK4 and type
      II receptor BMPR2 and the activation of Smad signaling pathway, which
      subsequently affected the proliferation, spread and apoptosis of cumulus cells.

PMID- 29587294
TI  - Macroscopic Localized Subicular Thinning as a Potential Indicator of Amyotrophic
      Lateral Sclerosis.
AB  - Subicular degeneration occurs in amyotrophic lateral sclerosis (ALS) patients.
      However, it was unknown whether microscopic subicular degeneration could be
      observed as macroscopic changes and whether these changes were associated with
      the transactive-response DNA binding protein 43 kDa (TDP-43) pathology.
      Topographic differences between subicular degeneration caused by ALS and
      Alzheimer disease (AD) had also not been characterized. Here we investigated the
      subiculum and related areas in autopsied brains from 3 ALS and 3 AD patients.
      Macroscopic subicular thinning and corresponding astrocytosis were pronounced in
      ALS compared to AD. This thinning was frequently accompanied by TDP-43 pathology
      in the transentorhinal cortex and nucleus accumbens. The preferential
      susceptibility of the perforant pathway to TDP-43 deposition may be an underlying
      cause of subicular thinning in ALS.

PMID- 29587295
TI  - Helicobacter pylori Eradication Therapy Ameliorates Latent Digestive Symptoms in
      Chronic Atrophic Gastritis.
AB  - BACKGROUND/AIMS: This study investigated the effect of Helicobacter pylori
      eradication therapy on latent digestive symptoms in chronic atrophic gastritis.
      METHODS: We enrolled 650 health checkup patients who underwent eradication
      therapy for chronic gastritis and completed a self-report questionnaire before
      and after the treatment between January 2014 and December 2016 at the Japanese
      Red Cross Society Kyoto Daiichi Hospital. RESULTS: H. pylori eradication therapy
      for chronic atrophic gastritis improved latent digestive symptoms, including both
      the acid reflux and dyspepsia components in the frequency scale for the symptoms
      of gastroesophageal reflux disease (FSSG) scores. The effect was sustained until
      1 year after the treatment. Higher FSSG scores (>=8 points) before H. pylori
      eradication therapy and age <70 years were significantly associated with the
      improvement of digestive symptoms after H. pylori eradication therapy.
      CONCLUSION: H. pylori eradication therapy may improve patients' quality of life
      through the resolution of latent abdominal symptoms.

PMID- 29587296
TI  - The Relationships of the Fractional Excretion of Uric Acid with Brachial-Ankle
      Pulse Wave Velocity and Ankle Brachial Index in Chinese Young Adults.
AB  - BACKGROUND/AIMS: Elevated serum uric acid (UA) was intimately correlated with
      vascular stiffness and abnormal ankle brachial index (ABI) in various
      populations. These correlations lost significance after adjustment for estimated
      glomerular filtration rate (eGFR), indicating that the association of UA and
      brachial-ankle pulse wave velocity (baPWV) or ABI might be driven by kidney
      function. UA is predominantly eliminated through the kidneys, and metabolic
      disorders can influence the clearance of UA. In this study, we aimed to explore
      the putative correlation between FEUA and baPWV or ABI to determine to what
      extent the associations with UA were affected by renal function. METHODS: This
      cross-sectional study enrolled 2351 participants, who underwent general health
      screening in Hanzhong people's hospital from March to June of 2017. BaPWV and ABI
      were measured using a volume-plethysmographic apparatus (BP-203RPEII; Nihon
      Colin, Tokyo, Japan). FEUA was divided into quartiles: Q1:FEUA<=3.07; Q2:
      3.07<FEUA<=5.32; Q3: 5.32<FEUA<=9.19; and Q4: FEUA> 9.19. RESULTS: Lower FEUA
      predicted a higher prevalence of high baPWV and low ABI (p for trend <0.001). The
      respective ORs for high baPWV from the first to the third quartiles of FEUA were
      1.777(1.323, 2.387); 1.561(1.158, 2.104); and 1.680 (1.250, 2.259). The
      prevalence of low ABI was greatly elevated with the decrement of FEUA [ORs for
      the first to third FEUA quartiles were 6.977(2.062, 23.610); 5.123(1.475,
      17.790); and 2.685(0.709, 10.171), respectively]. The association of FEUA and ABI
      was independent of related confounding factors. However, the association between
      FEUA and baPWV was greatly influenced by corresponding confounders, especially
      gender. The efficacy of FEUA in the prediction of low ABI was stronger than that
      of serum UA. However, serum UA was more powerful in the prediction of high baPWV.
      CONCLUSION: Kidney function exerted a profound influence on the relationship
      between UA and baPWV or ABI, revealing complex interactions among cardiovascular
      risk factors.

PMID- 29587297
TI  - A Prospective Trial of Nebulized Amikacin in the Treatment of Bronchiectasis
      Exacerbation.
AB  - BACKGROUND: Pseudomonas aeruginosa is the most common pathogenic bacteria in
      bronchiectasis (BE) patients. The availability and security of nebulized amikacin
      treatment are unknown. OBJECTIVE: The purpose of this study was to explore the
      efficiency and adverse effects of nebulized amikacin treatment for 2 weeks,
      administered as intravenous therapy during exacerbation of BE patients infected
      with P. aeruginosa. METHODS: A total of 143 patients with exacerbation of BE were
      screened between January 2013 and March 2016 at five tertiary hospitals in
      Shandong Province, China. The BE patients were diagnosed by high-resolution
      computed tomography scans, and all of them were confirmed to be infected with P.
      aeruginosa after sputum culture test. Seventy-four patients were assigned to the
      intervention group and received amikacin nebulization (0.2 g) treatment twice
      daily for 2 weeks along with intravenous antibiotic therapy. Sixty-nine patients
      were assigned to the control group and received standard antibiotic therapy
      alone. The primary outcome was the rate of bacterial eradication from the sputum,
      and the secondary outcomes were drug resistance and adverse effects. RESULTS: The
      bacterial eradication rate of sputum in the intervention group (51.4%) was
      significantly higher compared to that in the control group (23.2%) (chi2 =
      14.211, p = 0.030). Drug sensitivity testing showed that there were 5 drug
      resistant cases in the intervention group and 7 in the control group, which was
      not significantly different. Three patients dropped out of the trial due to
      adverse effects. None of the patients hat renal injury. CONCLUSIONS: Nebulized
      amikacin treatment is a safe treatment for exacerbation of BE and significantly
      increases the bacterial eradication rate of sputum.

PMID- 29587298
TI  - The Effect of and Mechanism Underlying Autophagy in Hepatocellular Carcinoma
      Induced by CH12, a Monoclonal Antibody Directed Against Epidermal Growth Factor
      Receptor Variant III.
AB  - BACKGROUND/AIMS: Epidermal growth factor receptor variant III (EGFRvIII), the
      most frequent EGFR variant, is constitutively activated without binding to EGF
      and is correlated with a poor prognosis. CH12, a human-mouse chimeric monoclonal
      antibody, has been developed in our laboratory and selectively binds to
      overexpressed EGFR and EGFRvIII. A previous study had reported that EGFR could
      influence autophagic activity, and autophagy is closely related to tumor
      development and the response to drug therapy. In this study, we aimed to
      elucidate the effect of CH12 on autophagy and efficacy of combining CH12 with an
      autophagy inhibitor against EGFRvIII-positive tumors. METHODS: EGFRvIII was
      overexpressed in liver cancer, glioblastoma and breast cancer, and the change in
      the autophagy-relevant protein levels was analyzed by western blot assays, LC3
      punctate aggregation was analyzed by immunofluorescence. The interaction of
      Beclin-1 and Rubicon was assessed by co-immunoprecipitation (Co-IP) after CH12
      treatment. The efficacy of ATG7 or Beclin-1 siRNA in combination with CH12 in Huh
      7-EGFRvIII cells was assessed by CCK-8 assays. The autophagy and apoptosis
      signaling events in Huh-7-EGFRvIII cells upon treatment with control, CH12, siRNA
      or combination for 48 h were assessed by western blot assays. RESULTS: Our
      results showed that, in cancer cell lines overexpressing EGFRvIII, only the liver
      cancer cell lines Huh-7 and PLC/PRF/5 suggested autophagy activation. We then
      investigated the mechanism of autophagy activation after EGFRvIII overexpression.
      The results showed that EGFRvIII interacted with Rubicon, an autophagy inhibition
      protein, and released Beclin-1 to form the inducer complex, thus contributing to
      autophagy. In addition, CH12, via inhibiting the phosphorylation of EGFRvIII,
      promoted the interaction of EGFRvIII with Rubicon, further inducing autophagy. In
      vitro assays suggested that knocking down the expression of the key proteins ATG7
      or Beclin-1 in the autophagy pathway with siRNA inhibits tumor cell
      proliferation. Combining autophagy-related proteins 7 (ATG7) or Beclin-1 siRNA
      with CH12 in Huh-7-EGFRvIII cells showed better inhibition of cell proliferation.
      CONCLUSION: EGFRvIII could induce autophagy, and CH12 treatment could improve
      autophagy activity in EGFRvIII-positive liver cancer cells. The combination of
      CH12 with an autophagy inhibitor or siRNA against key proteins in the autophagy
      pathway displayed more significant efficacy on EGFRvIII-positive tumor cells than
      monotherapy, and induced cell apoptosis.

PMID- 29587299
TI  - Chronic Obstructive Pulmonary Disease in Lung Cancer Patients: Prevalence,
      Underdiagnosis, and Clinical Characterization.
AB  - BACKGROUND: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are
      associated with increased morbidity and mortality. The differential clinical and
      functional features among LC patients with or without COPD have not been defined.
      OBJECTIVES: The aims of this study were to examine the prevalence and
      underdiagnosis rate of COPD in LC patients and to compare the clinical and
      functional features of LC patients with and without COPD. METHODS: We designed a
      multicenter hospital-based study including all LC cases diagnosed from January
      2014 to August 2016. We assessed epidemiological, clinical, radiological,
      functional, and histological variables in all cases. RESULTS: We recruited 602
      patients with LC, most of them men (77.9%), with a median age of 67 +/- 15 years.
      The COPD prevalence among LC patients was 51.5%, with a underdiagnosis rate of
      71.6%. The LC+COPD patients were older and the proportion of men was higher
      compared with the LC-only patients. The LC+COPD patients had more pack-years,
      more squamous LC, a lower monoxide transfer coefficient (KCO), and higher
      Charlson index scores than patients with LC only. The median survival of LC-only
      patients was 37% longer than that of LC+COPD patients (22 vs. 16 months), but
      this difference was not statistically significant. CONCLUSIONS: Among LC
      patients, COPD is prevalent and underdiagnosed. Patients with LC+COPD more often
      have squamous LC, have greater comorbidities, and have a lower KCO. More effort
      should be made for an early diagnosis of COPD to select patients at higher risk
      of developing LC.

PMID- 29587300
TI  - Audiology Students' Perspectives of Enacting and Learning Clinical Communication:
      A Qualitative Interview and Video Reflexivity Study.
AB  - Purpose: Effective clinical communication is pivotal to the provision of quality
      hearing health care. To date, audiology students reportedly felt ill-prepared
      when counseling patients about their hearing impairment, yet there is a paucity
      of studies exploring how clinical communication is taught and learned in
      audiology programs. Thus, the aims of the study were (a) to explore final year
      audiology students' perspectives of their own clinical communication skills
      during an in-house university clinical placement and (b) to explore students'
      perceptions of their clinical communication education. Method: Using a
      qualitative description approach, students were asked to coview their filmed
      clinical encounter using video reflexivity during a semistructured interview on
      clinical communication education. Fifteen final year graduate audiology students
      from The University of Melbourne, Australia, participated in the study. The
      interviews were audio-recorded and analyzed thematically. Results: The
      overarching themes of striving to be patient-centered, assessment shapes
      behavior, and power relations emerged from students' reflection of their own
      clinical encounter. In addition, the theme what students want described the
      perceived teaching methods that assisted students' clinical communication
      practices. Conclusions: The findings of this study highlight the challenges that
      students perceived during their clinical placement as they strive to enact a
      patient-centered interaction. An assessment rubric that incorporates
      communication skills can provide greater opportunities for feedback and self
      reflection. Additionally, clinical communication education that adopts
      experiential learning and is longitudinally integrated into the curriculum can
      further reinforce students' communication learning needs.

PMID- 29587301
TI  - The Effects of Parent Training on Vocabulary Scores of Young Children With
      Hearing Loss.
AB  - Purpose: The purpose of this study is to evaluate the effects of short-term
      parent training on maternal use of language stimulation strategies and vocabulary
      scores in children with hearing loss. Method: Six mother-child dyads participated
      in the multiple-baseline study. During baseline and maintenance, children engaged
      in a business-as-usual model of clinician-only therapy. During intervention,
      mothers and children participated in parent training focused on transparent
      labeling and linguistic mapping strategies. Parent strategy use was measured via
      weekly play-based probe assessments. Child vocabulary growth was measured via
      parent report. Results: A relation between parent training and use of transparent
      labeling was established for all mothers, and a relation between parent training
      and use of linguistic mapping was established for 3 of 6 mothers. Child
      vocabulary growth rate increased from baseline to intervention in 4 of 6
      children. Conclusions: Short-term parent training can change parent behavior.
      However, parents may not maintain these skills without support. Further research
      is needed to characterize the extent to which short-term training can make long
      term changes in parent and child outcomes.

PMID- 29587304
TI  - Vocal Emotion Identification by Children Using Cochlear Implants, Relations to
      Voice Quality, and Musical Interests.
AB  - Purpose: Listening tests for emotion identification were conducted with 8-17-year
      old children with hearing impairment (HI; N = 25) using cochlear implants, and
      their 12-year-old peers with normal hearing (N = 18). The study examined the
      impact of musical interests and acoustics of the stimuli on correct emotion
      identification. Method: The children completed a questionnaire with their
      background information and noting musical interests. They then listened to vocal
      stimuli produced by actors (N = 5) and consisting of nonsense sentences and
      prolonged vowels ([a:], [i:], and [u:]; N = 32) expressing excitement, anger,
      contentment, and fear. The children's task was to identify the emotions they
      heard in the sample by choosing from the provided options. Acoustics of the
      samples were studied using Praat software, and statistics were examined using
      SPSS 24 software. Results: The children with HI identified the emotions with 57%
      accuracy and the normal hearing children with 75% accuracy. Female listeners were
      more accurate than male listeners in both groups. Those who were implanted before
      age of 3 years identified emotions more accurately than others (p < .05). No
      connection between the child's audiogram and correct identification was observed.
      Musical interests and voice quality parameters were found to be related to
      correct identification. Conclusions: Implantation age, musical interests, and
      voice quality tended to have an impact on correct emotion identification. Thus,
      in developing the cochlear implants, it may be worth paying attention to the
      acoustic structures of vocal emotional expressions, especially the formant
      frequency of F3. Supporting the musical interests of children with HI may help
      their emotional development and improve their social lives.

PMID- 29587306
TI  - The Impact of Lexical Characteristics and Noise on Intelligibility of
      Parkinsonian Speech.
AB  - Purpose: This study investigated the impact of lexical characteristics on the
      intelligibility of speakers with Parkinson's disease (PD). Intelligibility was
      compared for listening in a quiet versus a noisy environment. Method: A total of
      192 young listeners participated in the study, with 96 listeners listening in
      quiet and 96 listening in noise in which the spoken sentences were mixed with 10
      talker babble. The listeners transcribed spoken sentences with target words
      controlled for word frequency and neighborhood density. The sentences were
      produced by 12 speakers with PD and 12 healthy control (HC) speakers.
      Transcription accuracy was compared across lexical categories between PD and HC
      and between the two listening conditions. Results: Transcription accuracy was
      higher for high-frequency words than low-frequency words for both speaker groups
      in quiet and in noise. The neighborhood density effect was evident only in the
      noise condition with better intelligibility for words from sparse neighborhoods
      than from dense neighborhoods. Regardless of listening condition, the PD group
      was less intelligible with a significant decrease in intelligibility in noise
      relative to quiet. Conclusions: The lexical properties of the words affected
      listeners' understanding of Parkinsonian speech. Frequent words in sparse
      neighborhood enhanced intelligibility, especially under adverse listening
      conditions. Babble noise had a detrimental impact on the intelligibility of
      Parkinsonian speech. The extent of the lexical effect on intelligibility
      increased in noise.

PMID- 29587307
TI  - Measuring the Diagnostic Features of Social (Pragmatic) Communication Disorder:
      An Exploratory Study.
AB  - Purpose: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
      introduced a new neurodevelopmental disorder, social (pragmatic) communication
      disorder (SPCD), that is characterized by deficits in 4 areas of communication.
      Although descriptions of these areas are provided, no assessment tools for SPCD
      are recommended. The purpose of this study was to examine the extent to which
      items from measurement tools commonly used in assessing pragmatic language
      impairment and related disorders might be useful in assessing the characteristics
      of social communication that define SPCD in the Diagnostic and Statistical Manual
      of Mental Disorders, Fifth Edition. Method: Based on a literature search, 594
      items from assessment tools commonly used to measure social communication
      abilities in people with pragmatic language impairment were identified. The first
      author judged whether each item reflected 1, more than 1, or none of the 4 SPCD
      diagnostic characteristics. After a brief training process, 5 second raters
      independently mapped subsets of items to the 6 categories. We calculated the
      percentage of agreement and Cohen's kappa for each pair of raters in assigning
      items to categories. Results: Percentages of agreement ranged from 76% to 82%,
      and Cohen's kappa values ranged from .69 to .76, indicating substantial
      agreement. Sources and item numbers for the 206 items that both raters assigned
      to the same SPCD feature are provided. Conclusions: These items may provide
      guidance in assessing SPCD and in designing standardized screening and diagnostic
      measures for SPCD.

PMID- 29587311
TI  - ?

PMID- 29587312
TI  - ?

PMID- 29587313
TI  - ?

PMID- 29587314
TI  - ?

PMID- 29587315
TI  - ?

PMID- 29587316
TI  - ?

PMID- 29587317
TI  - ?

PMID- 29587319
TI  - ?

PMID- 29587318
TI  - ?

PMID- 29587320
TI  - ?

PMID- 29587321
TI  - [Immunotherapy with checkpoint inhibitors in local advanced and metastatic
      urothelial carcinoma].
AB  - The approval of immune checkpoint inhibitors has started a new era in the
      treatment of urothelial carcinoma, which, so far, has been a disease with limited
      treatment options. However, in the current German S3 guideline for bladder cancer
      the remarkable improvements provided by immune checkpoint inhibitors have not
      been reflected. As cancer immunotherapy is a novel approach, there are several
      questions related to the daily clinical routine: What clinical data was used as
      the basis for the approval of the individual substances? What does this mean for
      previous treatment algorithms? What issues must be considered in the management
      of adverse events? What side-effects may occur and how can they be recognised and
      treated? The present paper provides an overview of the new treatment options
      regarding their relevance as well as recommendations for their application in
      clinical practice.

PMID- 29587322
TI  - [The role of biomarkers in the diagnosis, prognosis and therapy of patients with
      immuno-oncological treatments of genito-urinary carcinomas].
AB  - In recent years, fundamental research has yielded new insights into tumour
      biology, and new treatments have been developed. This review highlights the role
      of the pathologist and how he can support clinicians to find the right treatment
      for each patient. We explain the problems of the molecular subgroups of bladder
      cancer, the role of neo-adjuvant chemotherapy in the context of these findings,
      and show the important role of checkpoint inhibitors. Furthermore we focus on
      kidney cancer, with the clear cell carcinoma as the most frequent tumour type. We
      briefly consider prostate cancer, which as a hormone-dependent tumour probably
      requires different therapies. We also try to show the feasibility and the limits
      of pathology with the emerging tumour markers.

PMID- 29587323
TI  - [Immune checkpoint inhibition in metastatic urothelial carcinoma].
AB  - The treatment of metastatic urothelial carcinoma is characterized by the
      administration of combinatory regimes of chemotherapy. In the first-line
      treatment theses regimes demonstrate relatively good objective response rates and
      prolongation of overall survival. The prognosis declines if the patient is
      refractory to platin in the second- or third-line treatment or if the patient is
      ineligible for cisplatin in the first-line setting. Cisplatin ineligibility is
      defined by a poor renal function or subsequent comorbidities. The new class of
      immune checkpoint inhibitors (ICI) has led to an impressive improvement in the
      therapy of mUC in platin-refractory or cisplatin-ineligible patients. Currently,
      the EMA has approved Atezolizumab, Nivolumab and Pembrolizumab based on phase II
      and III trial data. Future developments focus on first-line and adjuvant
      treatment of ICI with PD-L1/PD-1 as a backbone and in combination with either
      other ICI or chemotherapy. The prognostic use of biomarkers in ICI is still a
      medical need as the currently available results with regard to the PD-L1 status
      are heterogeneous.

PMID- 29587324
TI  - [Immunotherapy for renal cell carcinoma - current status].
AB  - Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially
      changed during the last 2 years due to approval of the immune-checkpoint
      inhibitor Nivolumab (Opdivo(r)) and new multikinase inhibitors (Cabozantinib,
      Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends
      Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted
      therapy. CheckMate 025, the prospective randomized trial which led to approval of
      Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard
      ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable
      toxicity profile compared with Everolimus. Currently, numerous combinations with
      PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC.
      Out of these CheckMate 214, a randomized phase-3 trial is the first to
      demonstrate a significant higher objective response rate (42 % vs. 27 %, p <
      0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has
      been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of
      Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk
      patients. Furthermore, CheckMate 214 shows better side effect profile and quality
      of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib.
      However, a considerable increase of immune related adverse events is associated
      with the immune combination therapy. Another randomized trial demonstrates
      improved progression-free survival for the combination of the PD-L1 inhibitor
      Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive
      tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new"
      VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor
      combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor
      Nivolumab will remain a standard treatment for patients with metastatic renal
      cell carcinoma after prior VEGF targeted therapy. Nivolumab in combination with
      Ipilimumab will become a standard 1st line option for patients with intermediate
      and high risk profile according to IMDC. Further data are required regarding PD
      1/PD-L1 inhibitors in combination with Bevacizumab and VEGFR-TKIs, respectively,
      including overall survival and side effect profile.

PMID- 29587325
TI  - ?

PMID- 29587326
TI  - Video Comment on Zaheer Nabi et al.

PMID- 29587327
TI  - Video Comment on Vasilios Papastergiou et al.

PMID- 29587329
TI  - Cold snare polypectomy: is there a limit to polyp size?

PMID- 29587330
TI  - [French comment on article Peroral endoscopic myotomy in treatment-naive
      achalasia patients versus prior treatment failure cases].

PMID- 29587331
TI  - [French comment on article Purse-string transoral outlet reduction (TORe) is
      effective at inducing weight loss and improvement in metabolic comorbidities
      after Roux-en-Y gastric bypass].

PMID- 29587332
TI  - [French comment on article Aggressive intravenous hydration with lactated
      Ringer's solution for prevention of post-ERCP pancreatitis: a prospective
      randomized multicenter clinical trial].

PMID- 29587333
TI  - [French comment on article Cold versus hot endoscopic mucosal resection for
      nonpedunculated colorectal polyps sized 6-10 mm: a randomized trial].

PMID- 29587335
TI  - ?

PMID- 29587334
TI  - [French comment on article Simethicone improves bowel cleansing with low-volume
      polyethylene glycol: a multicenter randomized trial].

PMID- 29587336
TI  - Oral versus inhaled antibiotics for bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is a chronic inflammatory disease characterised by a
      recurrent cycle of respiratory bacterial infections associated with cough, sputum
      production and impaired quality of life. Antibiotics are the main therapeutic
      option for managing bronchiectasis exacerbations. Evidence suggests that inhaled
      antibiotics may be associated with more effective eradication of infective
      organisms and a lower risk of developing antibiotic resistance when compared with
      orally administered antibiotics. However, it is currently unclear whether
      antibiotics are more effective when administered orally or by inhalation.
      OBJECTIVES: To determine the comparative efficacy and safety of oral versus
      inhaled antibiotics in the treatment of adults and children with bronchiectasis.
      SEARCH METHODS: We identified studies through searches of the Cochrane Airways
      Group's Specialised Register (CAGR), which is maintained by the Information
      Specialist for the group. The Register contains trial reports identified through
      systematic searches of bibliographic databases including the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and
      PsycINFO, and handsearching of respiratory journals and meeting abstracts. We
      also searched ClinicalTrials.gov and the WHO trials portal. We searched all
      databases in March 2018 and imposed no restrictions on language of publication.
      SELECTION CRITERIA: We planned to include studies which compared oral antibiotics
      with inhaled antibiotics. We would have considered short-term use (less than four
      weeks) for treating acute exacerbations separately from longer-term use as a
      prophylactic (4 weeks or more). We would have considered both intraclass and
      interclass comparisons. We planned to exclude studies if the participants
      received continuous or high-dose antibiotics immediately before the start of the
      trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis,
      active allergic bronchopulmonary aspergillosis or active non-tuberculous
      Mycobacterial infection. DATA COLLECTION AND ANALYSIS: Two review authors
      independently applied study inclusion criteria to the searches and we planned for
      two authors to independently extract data, assess risk of bias and assess overall
      quality of the evidence using GRADE criteria. We also planned to obtain missing
      data from the authors where possible and to report results with 95% confidence
      intervals (CIs). MAIN RESULTS: We identified 313 unique records through database
      searches and a further 21 records from trial registers. We excluded 307 on the
      basis of title and abstract alone and a further 27 after examining full-text
      reports. No studies were identified for inclusion in the review. AUTHORS'
      CONCLUSIONS: There is currently no evidence indicating whether orally
      administered antibiotics are more beneficial compared to inhaled antibiotics. The
      recent ERS bronchiectasis guidelines provide a practical approach to the use of
      long-term antibiotics. New research is needed comparing inhaled versus oral
      antibiotic therapies for bronchiectasis patients with a history of frequent
      exacerbations, to establish which approach is the most effective in terms of
      exacerbation prevention, quality of life, treatment burden, and antibiotic
      resistance.

PMID- 29587337
TI  - Relationship between happiness and tobacco smoking among high school students.
AB  - OBJECTIVES: Recent research has described negative relationship between happiness
      and habitual smoking among adolescents. No study of this relationship has been
      conducted among Iranian adolescents. The aim of the present study was to
      characterize the relationship between happiness and cigarette or hookah smoking
      among a sample of high school students. METHODS: A sample of 1,161 10th-grade
      students in Tabriz (northwest Iran) was selected by multi-stage proportional
      cluster sampling. Participants completed a self-administered multiple-choice
      questionnaire including information on cigarette smoking, hookah smoking,
      happiness score, substance abuse, self-injury, general risk-taking behavior,
      attitudes towards smoking, socioeconomic information, and demographic
      characteristics. An ordinal logistic regression model was used for data analysis.
      RESULTS: It was found that 5.9 and 5.0% of students were regular cigarette
      smokers and regular hookah smokers, respectively. After controlling for potential
      confounders, higher happiness scores were found to protect students against more
      advanced stages of cigarette smoking (odds ratio [OR], 0.98; 95% confidence
      interval [CI], 0.97 to 0.99; p=0.013). However, no significant relationship was
      found between happiness scores and hookah smoking status (OR, 1.01; 95% CI, 0.97
      to 1.02; p=0.523). CONCLUSIONS: Happiness scores were associated with less
      advanced stages of habitual cigarette smoking among high school students. Our
      findings underscore the necessity of conducting longitudinal or interventional
      studies aiming to determine the effects of enhancing happiness on preventing the
      transition through the stages of cigarette and hookah smoking.

PMID- 29587338
TI  - Interpretation of the hygiene and microflora hypothesis for allergic diseases
      through epigenetic epidemiology.
AB  - The hygiene hypothesis (HH) proposed by Strachan in 1989 was expanded to explain
      the inverse association between the occurrence of allergy disorders and the risk
      of infectious diseases and parasite infestation. The microflora hypothesis (MH)
      suggests that gut microbial dysbiosis in early life might trigger
      hypersensitivity disorders. The sharing concept of both HH and MH is gene
      environment interaction, which is also a key concept in epigenetics. The
      amalgamation of epidemiology and epigenetics has created a scientific discipline
      termed epigenetic epidemiology. To accomplish an era of gene-environment-wide
      interaction studies, it is necessary to launch a national human epigenome
      project.

PMID- 29587339
TI  - Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by
      Suppressing AKT Phosphorylation and Decreasing Cyclin D1.
AB  - A type of breast cancer with a defect in three molecular markers such as the
      estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC
      have a lower survival rate than patients with other types due to a poor
      prognosis. In this study, we confirmed the anti-cancer effect of a natural
      compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed
      the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC
      cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular
      mechanism of this activity, we examined the signal transduction pathways after
      treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis
      but drastically inhibited AKT phosphorylation and reduced the amount of
      retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G
      induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently,
      Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no
      significant change in T47D cells except for a mild decrease in AKT
      phosphorylation. These results show that Gomisin G has an anti-cancer activity by
      suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study
      suggests that Gomisin G could be used as a therapeutic agent in the treatment of
      TNBC patients.

PMID- 29587340
TI  - Genetic Variations Associated with Sleep Disorders in Patients with
      Schizophrenia: A Systematic Review.
AB  - Background: Schizophrenic patients commonly suffer from sleep disorders which are
      associated with acute disease severity, worsening prognoses and a poorer quality
      of life. Research is attempting to disentangle the complex interplay between
      schizophrenia and sleep disturbances by focusing not only on demographic and
      clinical characteristics, but also on the identification of genetic factors.
      Methods: Here, we performed a systematic literature review on the topic of
      genetic variations in sleep-disordered schizophrenic patients in an attempt to
      identify high quality investigations reporting scientifically sound and
      clinically useful data. For this purpose, we conducted a thorough 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 11 eligible studies. Certain genetic
      variations were reported to be associated with schizophrenia-related sleep
      disorders. Antipsychotic-induced restless legs syndrome was linked to
      polymorphisms located on CLOCK, BTBD9, GNB3, and TH genes, clozapine-induced
      somnolence was correlated with polymorphisms of HNMT gene, while insomnia was
      associated with variants of the MTNR1 gene. Conclusions: There are significant
      genetic associations between schizophrenia and co-morbid sleep disorders,
      implicating the circadian system, dopamine and histamine metabolism and signal
      transduction pathways.

PMID- 29587341
TI  - Expression of Pinellia pedatisecta Lectin Gene in Transgenic Wheat Enhances
      Resistance to Wheat Aphids.
AB  - Wheat aphids are major pests during the seed filling stage of wheat. Plant
      lectins are toxic to sap-sucking pests such as wheat aphids. In this study,
      Pinellia pedatisecta agglutinin (ppa), a gene encoding mannose binding lectin,
      was cloned, and it shared 92.69% nucleotide similarity and 94% amino acid
      similarity with Pinellia ternata agglutinin (pta). The ppa gene, driven by the
      constitutive and phloem-specific ribulose bisphosphate carboxylase small subunit
      gene (rbcs) promoter in pBAC-rbcs-ppa expression vector, was transferred into the
      wheat cultivar Baofeng104 (BF104) by particle bombardment transformation. Fifty
      four T0 transgenic plants were generated. The inheritance and expression of the
      ppa gene were confirmed by PCR and RT-PCR analysis respectively, and seven
      homozygous transgenic lines were obtained. An aphid bioassay on detached leaf
      segments revealed that seven ppa transgenic wheat lines had lower aphid growth
      rates and higher inhibition rates than BF104. Furthermore, two-year aphid
      bioassays in isolated fields showed that aphid numbers per tiller of transgenic
      lines were significantly decreased, compared with wild type BF104. Therefore, ppa
      could be a strong biotechnological candidate to produce aphid-resistant wheat.

PMID- 29587342
TI  - Nutraceuticals for Skin Care: A Comprehensive Review of Human Clinical Studies.
AB  - The skin is the body's largest organ, it participates in sensitivity and offers
      protection against microorganisms, chemicals and ultraviolet (UV) radiation.
      Consequently, the skin may suffer alterations such as photo-ageing, immune
      dysfunction and inflammation which may significantly affect human health.
      Nutraceuticals represent a promising strategy for preventing, delaying, or
      minimising premature ageing of the skin and also to alleviate certain skin
      disorders. Among them, bioactive peptides and oligosaccharides, plant
      polyphenols, carotenoids, vitamins and polyunsaturated fatty acids are the most
      widely used ingredients. Supplementation with these products has shown evidence
      of having an effect on the signs of ageing and protection against UV radiation
      ageing in several human trials. In this review, the most relevant human studies
      on skin nutraceuticals are evaluated and the statistical resolution, biological
      relevance of their results, and, the trial protocols are discussed. In
      conclusion, quality and rigorousness of the trials must be improved to build
      credible scientific evidence for skin nutraceuticals and to establish a cause
      effect relationship between the ingredients the beneficial effects for the skin.

PMID- 29587343
TI  - Molecular Mechanisms of Melatonin Protection from Gastric Mucosal Apoptotic
      Injury in Experimental Burns.
AB  - Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional
      molecule. It has antioxidant and anti-apoptotic activities and protects tissues
      from injury. The objective of the present study was to determine the molecular
      mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn
      model. We hypothesized that melatonin gastric protection may be related to the
      activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30%
      total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was
      injected immediately and 12 h after thermal skin injury. Via light
      immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4
      HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related
      proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)).
      Thermal trauma in burned animals, compared with the controls, increased the
      expression of pro-apoptotic Bax protein (1.37 (0.94-1.47)), decreased anti
      apoptotic Bcl-2 protein (1.16 (1.06-1.23), p < 0.001) in epithelial cells, and
      elevated Bax/Bcl-2 ratios (p < 0.05). Tissue 4-HNE and Nrf2 levels were increased
      following severe burns (1.55 (0.98-1.61) and 1.16 (1.01-1.25), p < 0.05,
      respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74-0.96), p <
      0.01) and upregulated Nrf2 (1.55 (1.52-1.65), p < 0.001) levels. It also
      augmented Bax (1.68 (1.5-1.8), p < 0.001) and Bcl-2 expressions (1.96 (1.89
      2.01), p < 0.0001), but reduced Bax/Bcl-2 ratios (p < 0.05). Our results suggest
      that experimental thermal trauma induces oxidative gastric mucosal injury.
      Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid
      peroxidation attenuation, and Bax/Bcl-2 ratio modification as well.

PMID- 29587344
TI  - Economy of Catalyst Synthesis-Convenient Access to Libraries of Di- and
      Tetranaphtho Azepinium Compounds.
AB  - Efficient optimization procedures in chiral catalysis are usually linked to a
      straightforward strategy to access groups of structurally similar catalysts
      required for fine-tuning. The ease of building up such ligand libraries can be
      increased when the structure-modifying step (introduction of a substituent) is
      done at a later stage of the synthesis. This is demonstrated for the extended
      family of di- and tetranaphtho azepinium compounds, widely used as chiral phase
      transfer catalysts (PTC). Using 2,6-diiodo-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'
      e]azepine and 4,8-diiodo-6,7-dihydro-5H-dibenzo[c,e]azepine, respectively, as key
      intermediates, 18 spiro-azepinium compounds were synthesized in a total yield of
      25-42% over 6-7 steps from 1,1'-binaphthyl-2,2'-dicarboxylic acid or diphenic
      acid, respectively. The replacement of iodo groups with aryl substituents was
      performed as the last or the penultimate step of the synthesis.

PMID- 29587345
TI  - Multifunctional Fischer Aminocarbene Complexes as Hole or Electron Transporting
      Layers in Organic Solar Cells.
AB  - A new series of Fischer carbenes have been synthetized and examined as hole
      transporting or electron-transporting layers (HTLs or ETLs) in the fabrication of
      organic solar cells (OSCs). The synthesis of three Fischer aminocarbene complexes
      with the general formula [Cr(CO)5{C(NHCH2)Ar}] (Ar = 2-pyridyl (3a), 3-pyridyl
      (3b) and 4-pyridyl (3c)) is reported. The molecular structure of complex 3b has
      been confirmed by X-ray analysis. In order to study the possible applications of
      the three Fischer aminocarbenes in OSCs, thin films of these complexes were
      prepared using a vacuum deposition process. These organometallic films were
      chemically and morphologically characterized by IR spectroscopy, SEM, AFM and
      XRD. According to the IR and Tauc analysis, the vacuum deposition process
      generates thin films free of impurities with an activation energy of 4.0, 2.7 and
      2.1 eV for 3a, 3b y 3c, respectively. The UV-vis spectra of the amorphous
      aminocarbene films show that they are practically transparent to the visible
      radiation of the electromagnetic spectrum. This is due to the fact that their
      absorption is located mainly in the ultraviolet range. Two OSCs with bulk
      heterojunction configuration were manufactured in order to prove the use of the
      aminocarbenes as ETL o HTL. The aminocarbene [Cr(CO)5{C(NHCH2) 4-pyridyl}] (3c)
      proved to be suitable as ETL with a fill factor (FF) of 0.23 and a short circuit
      current density (JSC) of 1.037 mA/cm2.

PMID- 29587346
TI  - Spatiotemporal Characteristics and Health Risk Assessment of Heavy Metals in
      PM2.5 in Zhejiang Province.
AB  - The spatiotemporal characteristics and human health risks of 12 heavy metals (Al,
      As, Be, Cd, Cr, Hg, Mn, Ni, Pb, Sb, Se, and Tl) in fine particulate matter
      (PM2.5) in Zhejiang Province were investigated. The annual average PM2.5
      concentration was 58.83 ug/m3 in 2015 in Zhejiang. Element contents in PM2.5
      varied greatly with the season and locations. Al, Pb, and Mn were the most
      abundant elements among the studied metal(loid)s in PM2.5. The non-carcinogenic
      risks of the 12 elements through inhalation and dermal contact exposure were
      lower than the safe level for children and adults. However, there were potential
      non-carcinogenic risks of Tl, As, and Sb for children and Tl for adults through
      ingestion exposure. The carcinogenic risks from As, Be, Cd, Cr, Pb, and Ni
      through inhalation exposure were less than the acceptable level (1 * 10-4) for
      children and adults. Pb may carry a potential carcinogenic risk for both children
      and adults through ingestion. More attention should be paid to alleviate non
      carcinogenic and carcinogenic health risks posed by particle-bound toxic elements
      through ingestion exposure.

PMID- 29587348
TI  - Rhamnellosides A and B, omega-Phenylpentaene Fatty Acid Amide Diglycosides from
      the Fruits of Rhamnella franguloides.
AB  - Two new omega-phenylpentaene fatty acid amide diglycosides, rhamnellosides A (1)
      and B (2), were isolated from the fruits of Rhamnella franguloides (Rhamnaceae).
      These compounds were prioritized using LC-MS/MS molecular networking
      dereplication based on our previous discovery of 2-acetoxy-omega-phenylpentaene
      fatty acid triglycosides berchemiosides A-C from a phylogenetically related
      species, Berchemia berchemiifolia. The structures of the isolated compounds were
      elucidated by spectroscopic analyses in combination with chemical derivatization.
      The pentaene groups of 1 and 2 were found to have (6E, 8E, 10Z, 12Z, 14E)
      geometry, which is the same as that found in berchemioside A.

PMID- 29587347
TI  - Survivin-Based Treatment Strategies for Squamous Cell Carcinoma.
AB  - Survivin, an anti-apoptotic molecule abundantly expressed in most human
      neoplasms, has been reported to contribute to cancer initiation and drug
      resistance in a wide variety of human tumors. Efficient downregulation of
      survivin can sensitize tumor cells to various therapeutic interventions,
      generating considerable efforts in its validation as a new target in cancer
      therapy. This review thoroughly analyzes up-to-date information on the potential
      of survivin as a therapeutic target for new anticancer treatments. The literature
      dealing with the therapeutic targeting of survivin will be reviewed, discussing
      specifically squamous cell carcinomas (SCCs), and with emphasis on the last
      clinical trials. This review gives insight into the recent developments
      undertaken in validating various treatment strategies that target survivin in
      SCCs and analyze the translational possibility, identifying those strategies that
      seem to be the closest to being incorporated into clinical practice. The most
      recent developments, such as dominant-negative survivin mutants, RNA
      interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide
      based immunotherapy, seem to be helpful for effectively downregulating survivin
      expression and reducing tumor growth potential, increasing the apoptotic rate,
      and sensitizing tumor cells to chemo- and radiotherapy. However, selective and
      efficient targeting of survivin in clinical trials still poses a major challenge.

PMID- 29587349
TI  - Evaluation of Two Liver Treatment Strategies in a Mouse Model of Niemann-Pick
      Disease Type C1.
AB  - Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage
      disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and
      hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid
      metabolism-related genes in NPC1 disease are still poorly understood. Here, we
      used an NPC1 mouse model to study an additive hepatoprotective effect of a
      combination of 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD), miglustat and
      allopregnanolone (combination therapy) with the previously established
      monotherapy using HPbetaCD. We examined transgene effects as well as treatment
      effects on liver morphology and hepatic lipid metabolism, focusing on hepatic
      cholesterol transporter genes. Livers of Npc1-/- mice showed hepatic cholesterol
      sequestration with consecutive liver injury, an increase of lipogenetic gene
      expression, e.g., HMG-CoA, a decrease of lipolytic gene expression, e.g.,
      pparalpha and acox1, and a decrease of lipid transporter gene expression, e.g.,
      acat1, abca1 and fatp2. Both, combination therapy and monotherapy, led to a
      reduction of hepatic lipids and an amelioration of NPC1 liver disease symptoms.
      Monotherapy effects were related to pparalpha- and acox1-associated
      lipolysis/beta-oxidation and to fatp2-induced fatty acid transport, whereas the
      combination therapy additionally increased the cholesterol transport via abca1
      and apoE. However, HPbetaCD monotherapy additionally increased cholesterol
      synthesis as indicated by a marked increase of the HMG-CoA and srebp-2 mRNA
      expression, probably as a result of increased hepatocellular proliferation.

PMID- 29587350
TI  - Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin.
AB  - Despite the promising biological and antioxidant properties of curcumin, its
      medical applications are limited due to poor solubility in water and low
      bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may
      overcome these drawbacks. Properties such as particle size, zeta potential,
      morphology and encapsulation efficiency were assessed. Then, the possibility of
      storing these NPs in a solid-state form obtained by freeze-drying, in vitro
      curcumin dissolution and cytocompatibility towards intestinal cells were
      evaluated. Curcumin-loaded Eudragit(r) RLPO (ERL) NPs showed smaller particle
      diameters (245 +/- 2 nm) and better redispersibility after freeze-drying than
      either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The
      former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA
      or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid
      curcumin release with 91 +/- 5% released over 1 h. The three curcumin-loaded NPs
      proposed in this work were also compatible with intestinal cells. Overall, ERL
      NPs are the most promising vehicles for increasing the oral bioavailability of
      curcumin.

PMID- 29587351
TI  - Physicochemical Characterization and Antioxidant Activity of Humic Acids Isolated
      from Peat of Various Origins.
AB  - Although humic acids (HAs) from peat exhibit various therapeutic properties,
      there is little information available concerning their physicochemical and
      antioxidant properties. To address this issue, nine different types of peat,
      including oligotrophic, mesotrophic, and minerotrophic peat samples, were used
      for isolation of HA fractions by basic (HAb) and pyrophosphate (HAp) extractions.
      Physical parameters of the HAs were analyzed by UV-Vis, fluorescent, infrared
      (IR), and electron paramagnetic resonance (EPR) spectroscopy. Average Mr of the
      fractions ranged from 17.2 to 39.7 kDa, while their humification index (HIX)
      varied from 0.49 to 1.21. HAp fractions had a higher content of aromatic
      structures compared to HAb fractions. Moreover, HAp fractions had a significantly
      higher content of phenolic OH groups (3.6 +/- 0.5 mmol/g) versus HAb (3.1 +/- 0.5
      mmol/g). All HA fractions exhibited antioxidant activity in radical scavenging
      and electrochemical assays, and their EPR signal had a single line with g =
      2.0035, which is consistent with semiquinone type radicals. Furthermore, the HIX
      was found to be important in determining the number of semiquinone-type free
      radicals in the HA structures. Overall, these data provide a molecular basis to
      explain at least part of the beneficial therapeutic properties of peat-derived
      HAs.

PMID- 29587353
TI  - Implementation of a Medication Reconciliation Process in an Internal Medicine
      Clinic at an Academic Medical Center.
AB  - Discrepancies in medication orders at transitions of care have been shown to
      affect patient outcomes in a negative way. The Joint Commission recognizes the
      importance of medication reconciliation through their National Patient Safety
      Goals, with an emphasis placed on maintaining accurate medication information for
      each patient. The primary objective of this study was to assess the effectiveness
      of implementing a medication reconciliation process in an internal medicine
      clinic at an academic medical center. A retrospective chart review of patients
      seen at an Internal Medicine Clinic within and Academic Medical Center, a
      continuity and teaching clinic for Internal Medicine residents and faculty
      practice clinic, was conducted. Nursing staff were educated by PharmDs to perform
      a standardized medication history during the triage process. Medication
      reconciliation data was analyzed for 3263 patients from 1 August 2014 to 27
      February 2015. A total of 4479 discrepancies were found through this process,
      with the majority (71%) of discrepancies being medications on the list that
      patient was no longer taking. This project illustrated to our nursing and
      physician staff the need for regular thorough review of the patient medication
      list.

PMID- 29587352
TI  - MFAM: Multiple Frequency Adaptive Model-Based Indoor Localization Method.
AB  - This paper presents MFAM (Multiple Frequency Adaptive Model-based localization
      method), a novel model-based indoor localization method that is capable of using
      multiple wireless signal frequencies simultaneously. It utilizes indoor
      architectural model and physical properties of wireless signal propagation
      through objects and space. The motivation for developing multiple frequency
      localization method lies in the future Wi-Fi standards (e.g., 802.11ah) and the
      growing number of various wireless signals present in the buildings (e.g., Wi-Fi,
      Bluetooth, ZigBee, etc.). Current indoor localization methods mostly rely on a
      single wireless signal type and often require many devices to achieve the
      necessary accuracy. MFAM utilizes multiple wireless signal types and improves the
      localization accuracy over the usage of a single frequency. It continuously
      monitors signal propagation through space and adapts the model according to the
      changes indoors. Using multiple signal sources lowers the required number of
      access points for a specific signal type while utilizing signals, already present
      in the indoors. Due to the unavailability of the 802.11ah hardware, we have
      evaluated proposed method with similar signals; we have used 2.4 GHz Wi-Fi and
      868 MHz HomeMatic home automation signals. We have performed the evaluation in a
      modern two-bedroom apartment and measured mean localization error 2.0 to 2.3 m
      and median error of 2.0 to 2.2 m. Based on our evaluation results, using two
      different signals improves the localization accuracy by 18% in comparison to 2.4
      GHz Wi-Fi-only approach. Additional signals would improve the accuracy even
      further. We have shown that MFAM provides better accuracy than competing methods,
      while having several advantages for real-world usage.

PMID- 29587354
TI  - Folinic Acid Increases Protein Arginine Methylation in Human Endothelial Cells.
AB  - Elevated plasma total homocysteine (tHcy) is associated with increased risk of
      cardiovascular disease, but the mechanisms underlying this association are not
      completely understood. Cellular hypomethylation has been suggested to be a key
      pathophysiologic mechanism, since S-adenosylhomocysteine (AdoHcy), the Hcy
      metabolic precursor and a potent inhibitor of methyltransferase activity,
      accumulates in the setting of hyperhomocysteinemia. In this study, the impact of
      folate and methionine on intracellular AdoHcy levels and protein arginine
      methylation status was studied. Human endothelial cells were incubated with
      increasing concentrations of folinic acid (FnA), a stable precursor of folate,
      with or without methionine restriction. The levels of intracellular AdoHcy and
      AdoMet, tHcy in the cell culture medium, and protein-incorporated methylarginines
      were evaluated by suitable liquid chromatography techniques. FnA supplementation,
      with or without methionine restriction, reduced the level of tHcy and did not
      affect intracellular AdoMet levels. Interestingly, FnA supplementation reduced
      intracellular AdoHcy levels only in cells grown under methionine restriction.
      Furthermore, these cells also displayed increased protein arginine methylation
      status. These observations suggest that folic acid supplementation may enhance
      cellular methylation capacity under a low methionine status. Our results lead us
      to hypothesize that the putative benefits of folic acid supplementation in
      restoring endothelial homeostasis, thus preventing atherothrombotic events,
      should be reevaluated in subjects under a methionine restriction diet.

PMID- 29587356
TI  - Dietary Patterns and Their Relationship with Frailty in Functionally Independent
      Older Adults.
AB  - The impact of dietary patterns rather than single foods or nutrients on health
      outcomes is increasingly recognized. This cross-sectional study examines the
      dietary patterns of 527 non-institutionalized functionally independent older
      people aged >=70 years from Gipuzkoa (Spain). Sociodemographic characteristics,
      health status, anthropometric measures and dietary data are collected. Multiple
      correspondence analysis (MCA) and cluster analysis are performed to identify
      dietary patterns and groups of individuals. Frequency of selected food items and
      compliance with food recommendations are included in the MCA. A high proportion
      of the sample population are overweight or obese, whereas only 3.3% are at risk
      of malnutrition (determined with the Mini Nutritional Assessment). Frail
      individuals (n = 130), measured with the Timed-Up and Go test are older, have a
      lower educational level, are more obese, present a poorer health status (more
      depressive symptoms, polypharmacy and falls, among others) and worse compliance
      with food recommendations than robust individuals (n = 392). Three groups of
      individuals are identified: cluster one (n = 285), cluster two (n = 194) and
      cluster three (n = 48). A gradient of increasing frailty and poorer health status
      is observed from cluster one to cluster three. The latter also shows the poorest
      dietary pattern, regarding dietary recommendations. The use of an easy-to-use
      tool to assess diet allows detection of differences among the three clusters.
      There is a need to increase awareness on the implementation of nutritional
      screening and a subsequent dietary assessment in primary care settings to provide
      nutritional care to elder, and moreover, frail individuals.

PMID- 29587357
TI  - Importance of Footwear for Preventing Xerosis and Hyperkeratosis in Older People
      with Psychiatric Disorders Living in an Institution.
AB  - Few studies have focused on the relation between the use and characteristics of
      footwear and the presence of foot lesions in people with psychiatric disorders.
      This work analyzes the influence of different footwear habits on the presence of
      deformities and ungueal and dermal pathologies of the foot of institutionalized
      people with psychiatric disorders compared to people without these disorders. A
      transversal and observational study was conducted on 107 participants, divided
      into two groups who have used different types of shoes throughout their lives.
      The control group comprised 63 autonomous people who mainly use leather footwear
      and a study group of 44 institutionalized people with intellectual disabilities
      and psychiatric disorders who mainly use textile footwear. There were significant
      differences between populations. The group with psychiatric disorders presented
      more xerosis and hyperkeratosis. Footwear with inappropriate characteristics is a
      possible causal agent of skin alterations. Wearing footwear with quality textile
      uppers, e.g., fabric or felt, could influence the appearance of these
      alterations. Leather footwear is recommended for institutionalized people to
      reduce symptoms of xerosis and improve their quality of life.

PMID- 29587355
TI  - Rationale for Dietary Antioxidant Treatment of ADHD.
AB  - Increasing understanding arises regarding disadvantages of stimulant medication
      in children with ADHD (Attention-Deficit Hyperactivity Disorder). This review
      presents scientific findings supporting dietary antioxidant treatment of ADHD and
      describes substantial alterations in the immune system, epigenetic regulation of
      gene expression, and oxidative stress regulation in ADHD. As a result, chronic
      inflammation and oxidative stress could develop, which can lead to ADHD symptoms,
      for example by chronic T-cell-mediated neuroinflammation, as well as by neuronal
      oxidative damage and loss of normal cerebral functions. Therefore, modulation of
      immune system activity and oxidant-antioxidant balance using nutritional
      approaches might have potential in ADHD treatment. The use of natural
      antioxidants against oxidative conditions is an emerging field in the management
      of neurodegenerative diseases. Dietary polyphenols, for example, have antioxidant
      capacities as well as immunoregulatory effects and, therefore, appear appropriate
      in ADHD therapy. This review can stimulate the development and investigation of
      dietary antioxidant treatment in ADHD, which is highly desired.

PMID- 29587358
TI  - Surface Texture-Based Surface Treatments on Ti6Al4V Titanium Alloys for
      Tribological and Biological Applications: A Mini Review.
AB  - Surface texture (ST) has been confirmed as an effective and economical surface
      treatment technique that can be applied to a great range of materials and
      presents growing interests in various engineering fields. Ti6Al4V which is the
      most frequently and successfully used titanium alloy has long been restricted in
      tribological-related operations due to the shortcomings of low surface hardness,
      high friction coefficient, and poor abrasive wear resistance. Ti6Al4V has
      benefited from surface texture-based surface treatments over the last decade.
      This review begins with a brief introduction, analysis approaches, and processing
      methods of surface texture. The specific applications of the surface texture
      based surface treatments for improving surface performance of Ti6Al4V are
      thoroughly reviewed from the point of view of tribology and biology.

PMID- 29587360
TI  - Photocatalytic Activity of Nanotubular TiO2 Films Obtained by Anodic Oxidation: A
      Comparison in Gas and Liquid Phase.
AB  - The availability of immobilized nanostructured photocatalysts is of great
      importance in the purification of both polluted air and liquids (e.g., industrial
      wastewaters). Metal-supported titanium dioxide films with nanotubular morphology
      and good photocatalytic efficiency in both environments can be produced by anodic
      oxidation, which avoids release of nanoscale materials in the environment. Here
      we evaluate the effect of different anodizing procedures on the photocatalytic
      activity of TiO2 nanostructures in gas and liquid phases, in order to identify
      the most efficient and robust technique for the production of TiO2 layers with
      different morphologies and high photocatalytic activity in both phases. Rhodamine
      B and toluene were used as model pollutants in the two media, respectively. It
      was found that the role of the anodizing electrolyte is particularly crucial, as
      it provides substantial differences in the oxide specific surface area:
      nanotubular structures show remarkably different activities, especially in gas
      phase degradation reactions, and within nanotubular structures, those produced by
      organic electrolytes lead to better photocatalytic activity in both conditions
      tested.

PMID- 29587359
TI  - Down Syndrome, Obesity, Alzheimer's Disease, and Cancer: A Brief Review and
      Hypothesis.
AB  - Down syndrome (trisomy 21), a complex mix of physical, mental, and biochemical
      issues, includes an increased risk of Alzheimer's disease and childhood leukemia,
      a decreased risk of other tumors, and a high frequency of overweight/obesity.
      Certain features related to the third copy of chromosome 21 (which carries the
      APP gene and several anti-angiogenesis genes) create an environment favorable for
      Alzheimer's disease and unfavorable for cancer. This environment may be enhanced
      by two bioactive compounds from fat cells, leptin, and adiponectin. This paper
      outlines these fat-related disease mechanisms and suggests new avenues of
      research to reduce disease risk in Down syndrome.

PMID- 29587361
TI  - Endophytic Mycoflora and Their Bioactive Compounds from Azadirachta Indica: A
      Comprehensive Review.
AB  - Plants are all inhabited by endophytic fungi in the interior of their tissues.
      The neem tree Azadirachta is an Indian lilac used for various therapeutic
      purposes in different forms of preparations. This plant hosts different types of
      endophytic fungi. In some cases, different tissues of a given plant are inhabited
      by different endophytic fungi which are discussed in this paper. Recently, there
      have been new reports on endophytic fungi and their bioactive compounds from
      Azadirachta indica. The biological function of bioactive compounds was discussed
      in view of their future industrial prospects. There are a number of different
      research investigations that examine the endophytes isolated and screened for
      their potential bioactive secondary metabolites from neem, but there is no
      comprehensive review on neem endophytes and their secondary metabolites to bring
      all trends from different researchers together. Therefore, in this review, we
      have discussed the endophytic fungi from the different tissues of neem, in view
      of the latest understandings of antimicrobial, antioxidant, and pathogenicity
      target compounds. Importantly, tracing the previous findings would pave the way
      to forecast the missing link for future work by researchers.

PMID- 29587362
TI  - OTA Prevention and Detoxification by Actinobacterial Strains and Activated Carbon
      Fibers: Preliminary Results.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and
      Penicillium that contaminate food and feed raw materials. To reduce OTA
      contamination, we first tested in vitro, actinobacterial strains as potential
      biocontrol agents and afterward, through a physical decontamination method using
      activated carbon fibers (ACFs). Actinobacterial strains were screened for their
      ability to reduce OTA in solid co-culture with A. carbonarius, which is the major
      OTA-producing species in European vineyards. Four strains showed a high affinity
      for removing OTA (67%-83%) with no significant effect on fungal growth (<20%).
      The mechanism of action was first studied by analyzing the expression of OTA
      cluster genes (acOTApks, acOTAnrps, acOTAhal) by RT-qPCR showing a drastic
      reduction in all genes (7-15 times). Second, the ability of these strains to
      degrade OTA was assessed in vitro on ISP2 solid medium supplemented with OTA (100
      ug/L). Two strains reduced OTA to undetectable levels. As for the physical
      method, high adsorption rates were obtained for ACFs at 0.8 g/L with a 50%
      adsorption of OTA in red wine by AC15 and 52% in grape juice by AC20 within 24 h.
      These promising methods could be complementarily applied toward reducing OTA
      contamination in food chains, which promotes food safety and quality.

PMID- 29587363
TI  - Human-Like Neutralizing Antibodies Protect Mice from Aerosol Exposure with
      Western Equine Encephalitis Virus.
AB  - Western equine encephalitis virus (WEEV) causes symptoms in humans ranging from
      mild febrile illness to life-threatening encephalitis, and no human medical
      countermeasures are licensed. A previous study demonstrated that immune serum
      from vaccinated mice protected against lethal WEEV infection, suggesting the
      utility of antibodies for pre- and post-exposure treatment. Here, three
      neutralizing and one binding human-like monoclonal antibodies were evaluated
      against WEEV aerosol challenge. Dose-dependent protection was observed with two
      antibodies administered individually, ToR69-3A2 and ToR68-2C3. In vitro
      neutralization was not a critical factor for protection in this murine model, as
      ToR69-3A2 is a strong neutralizing antibody, and ToR68-2C3 is a non-neutralizing
      antibody. This result highlights the importance of both neutralizing and non
      neutralizing antibodies in the protection of mice from WEEV lethality.

PMID- 29587364
TI  - Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt
      Mediated Phospholamban Phosphorylation.
AB  - Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac
      arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its
      cardioprotection is diminished when delay in reaching the target temperature
      occurs. Baicalein, a flavonoid derived from the root of
      ScutellariabaicalensisGeorgi, possesses antioxidant properties. Therefore, we
      hypothesized that baicalein can rescue cooling cardioprotection when cooling is
      delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h
      reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used
      to assess cell survival and contractility, respectively. Cooling (32  degrees C)
      was initiated either during ischemia or during reperfusion. Cell viability and
      ROS generation were measured. Cell contractility was evaluated by real-time phase
      contrast imaging. Our results showed that cooling reduced cell death and ROS
      generation, and this effect was diminished when cooling was delayed. Baicalein
      (25 uM), given either at the start of reperfusion or start of cooling, resulted
      in a comparable reduction of cell death and ROS production. Baicalein improved
      phospholamban phosphorylation, contractility recovery, and cell survival. These
      effects were Akt-dependent. In addition, no synergistic effect was observed with
      the combined treatments of cooling and baicalein. Our data suggest that baicalein
      may serve as a novel adjunct therapeutic strategy for SCA resuscitation.

PMID- 29587365
TI  - Green, Hydrothermal Synthesis of Fluorescent Carbon Nanodots from Gardenia,
      Enabling the Detection of Metronidazole in Pharmaceuticals and Rabbit Plasma.
AB  - Strong fluorescent carbon nanodots (FCNs) were synthesized with a green approach
      using gardenia as a carbon source through a one-step hydrothermal method. FCNs
      were characterized by their UV-vis absorption spectra, photoluminescence (PL),
      Fourier transform infrared spectroscopy (FTIR) as well as X-ray photoelectron
      spectroscopy (XPS). We further explored the use of as-synthesized FCNs as an
      effective probe for the detection of metronidazole (MNZ), which is based on MNZ
      induced fluorescence quenching of FCNs. The proposed method displayed a wide
      linear range from 0.8 to 225.0 uM with a correlation coefficient of 0.9992 and a
      limit of detection as low as 279 nM. It was successfully applied to the
      determination of MNZ in commercial tablets and rabbit plasma with excellent
      sensitivity and selectivity, which indicates its potential applications in
      clinical analysis and biologically related studies.

PMID- 29587366
TI  - Efficient Proximity Computation Techniques Using ZIP Code Data for Smart Cities
      ?.
AB  - In this paper, we are interested in computing ZIP code proximity from two
      perspectives, proximity between two ZIP codes (Ad-Hoc) and neighborhood proximity
      (Top-K). Such a computation can be used for ZIP code-based target marketing as
      one of the smart city applications. A naive approach to this computation is the
      usage of the distance between ZIP codes. We redefine a distance metric combining
      the centroid distance with the intersecting road network between ZIP codes by
      using a weighted sum method. Furthermore, we prove that the results of our
      combined approach conform to the characteristics of distance measurement. We have
      proposed a general and heuristic approach for computing Ad-Hoc proximity, while
      for computing Top-K proximity, we have proposed a general approach only. Our
      experimental results indicate that our approaches are verifiable and effective in
      reducing the execution time and search space.

PMID- 29587368
TI  - Efficacy of Praziquantel in the Treatment of Platynosomum fastosum in Cats with
      Natural Infections.
AB  - Treatments for Platynosomum fastosum-the liver fluke of cats-have been developed
      based on fecal egg counts. Post mortem fluke counts are required to understand
      true efficacy. In this study, two praziquantel treatment regimens were evaluated
      using post mortem fluke counts: a high-dose treatment (HT) of 20 mg/kg body
      weight (BW) administered intramuscularly (IM) once a day for three consecutive
      days and a low-dose treatment (LT) of 5 mg/kg BW administered once (IM) and
      repeated 14 days later. A continual enrolment study design was used with 16
      naturally infected cats randomly allocated in blocks of four to the HT (eight
      cats) or LT (eight cats) group. Treatment success, defined as absence of live
      flukes post mortem, was determined 10 days after the last treatment. Pre- and
      post-treatment fecal egg counts (centrifugation with Sheather's sugar flotation
      solution) and bile egg counts (obtained via percutaneous ultrasound guided
      cholecystocentesis) were evaluated as supportive efficacy data. Twelve cats
      completed the study with two cats withdrawn from each group. Neither treatment
      was 100% effective. In the HT group, three of six cats had live flukes, albeit
      low numbers, at post mortem, while all six LT group cats had live flukes. While
      fecal and bile egg counts were reduced in both group, they were not reflective of
      the true infection status of the cats post mortem.

PMID- 29587369
TI  - An SCFFBXO28 E3 Ligase Protects Pancreatic beta-Cells from Apoptosis.
AB  - Loss of pancreatic beta-cell function and/or mass is a central hallmark of all
      forms of diabetes but its molecular basis is incompletely understood. beta-cell
      apoptosis contributes to the reduced beta-cell mass in diabetes. Therefore, the
      identification of important signaling molecules that promote beta-cell survival
      in diabetes could lead to a promising therapeutic intervention to block beta-cell
      decline during development and progression of diabetes. In the present study, we
      identified F-box protein 28 (FBXO28), a substrate-recruiting component of the
      Skp1-Cul1-F-box (SCF) ligase complex, as a regulator of pancreatic beta-cell
      survival. FBXO28 was down-regulated in beta-cells and in isolated human islets
      under diabetic conditions. Consistently, genetic silencing of FBXO28 impaired
      beta-cell survival, and restoration of FBXO28 protected beta-cells from the
      harmful effects of the diabetic milieu. Although FBXO28 expression positively
      correlated with beta-cell transcription factor NEUROD1 and FBXO28 depletion also
      reduced insulin mRNA expression, neither FBXO28 overexpression nor depletion had
      any significant impact on insulin content, glucose-stimulated insulin secretion
      (GSIS) or on other genes involved in glucose sensing and metabolism or on
      important beta-cell transcription factors in isolated human islets. Consistently,
      FBXO28 overexpression did not further alter insulin content and GSIS in freshly
      isolated islets from patients with type 2 diabetes (T2D). Our data show that
      FBXO28 improves pancreatic beta-cell survival under diabetogenic conditions
      without affecting insulin secretion, and its restoration may be a novel
      therapeutic tool to promote beta-cell survival in diabetes.

PMID- 29587367
TI  - Mammalian Plakins, Giant Cytolinkers: Versatile Biological Functions and Roles in
      Cancer.
AB  - Cancer is a highly lethal disease that is characterized by aberrant cell
      proliferation, migration, and adhesion, which are closely related to the dynamic
      changes of cytoskeletons and cytoskeletal-adhesion. These will further result in
      cell invasion and metastasis. Plakins are a family of giant cytolinkers that
      connect cytoskeletal elements with each other and to junctional complexes. With
      various isoforms composed of different domain structures, mammalian plakins are
      broadly expressed in numerous tissues. They play critical roles in many cellular
      processes, including cell proliferation, migration, adhesion, and signaling
      transduction. As these cellular processes are key steps in cancer development,
      mammalian plakins have in recent years attracted more and more attention for
      their potential roles in cancer. Current evidence shows the importance of
      mammalian plakins in various human cancers and demonstrates mammalian plakins as
      potential biomarkers for cancer. Here, we introduce the basic characteristics of
      mammalian plakins, review the recent advances in understanding their biological
      functions, and highlight their roles in human cancers, based on studies performed
      by us and others. This will provide researchers with a comprehensive
      understanding of mammalian plakins, new insights into the development of cancer,
      and novel targets for cancer diagnosis and therapy.

PMID- 29587370
TI  - Stakeholders' Perceptions of Agronomic Iodine Biofortification: A SWOT-AHP
      Analysis in Northern Uganda.
AB  - Agronomic biofortification (i.e., the application of fertilizer to elevate
      micronutrient concentrations in staple crops) is a recent strategy recommended
      for controlling Iodine Deficiency Disorders (IDDs). However, its success
      inevitably depends on stakeholders' appreciation and acceptance of it. By taking
      Northern Uganda as a case, this study aimed to capture and compare the
      perceptions of seven key stakeholder groups with respect to agronomic iodine
      biofortification. Therefore, we employed a SWOT (Strength, Weaknesses,
      Opportunities & Threats) analysis in combination with an Analytical Hierarchy
      Process (AHP). Findings show that stakeholders (n = 56) are generally positive
      about agronomic iodine biofortification in Uganda, as its strengths and
      opportunities outweighed weaknesses and threats. Cultural acceptance and
      effectiveness are considered the most important strengths while the high IDD
      prevalence rate and the availability of iodine deficient soils are key
      opportunities for further developing agronomic iodine biofortification.
      Environmental concerns about synthetic fertilizers as well as the time needed to
      supply iodine were considered crucial weaknesses. The limited use of fertilizer
      in Uganda was the main threat. While this study provides insight into important
      issues and priorities for iodine biofortification technology in Uganda, including
      differences in stakeholder views, the application of the SWOT-AHP method will
      guide future researchers and health planners conducting stakeholder analysis in
      similar domains.

PMID- 29587371
TI  - Building Change Detection from Bi-Temporal Dense-Matching Point Clouds and Aerial
      Images.
AB  - In this work, a novel building change detection method from bi-temporal dense
      matching point clouds and aerial images is proposed to address two major
      problems, namely, the robust acquisition of the changed objects above ground and
      the automatic classification of changed objects into buildings or non-buildings.
      For the acquisition of changed objects above ground, the change detection problem
      is converted into a binary classification, in which the changed area above ground
      is regarded as the foreground and the other area as the background. For the
      gridded points of each period, the graph cuts algorithm is adopted to classify
      the points into foreground and background, followed by the region-growing
      algorithm to form candidate changed building objects. A novel structural feature
      that was extracted from aerial images is constructed to classify the candidate
      changed building objects into buildings and non-buildings. The changed building
      objects are further classified as "newly built", "taller", "demolished", and
      "lower" by combining the classification and the digital surface models of two
      periods. Finally, three typical areas from a large dataset are used to validate
      the proposed method. Numerous experiments demonstrate the effectiveness of the
      proposed algorithm.

PMID- 29587372
TI  - Optimize the Coverage Probability of Prediction Interval for Anomaly Detection of
      Sensor-Based Monitoring Series.
AB  - Effective anomaly detection of sensing data is essential for identifying
      potential system failures. Because they require no prior knowledge or accumulated
      labels, and provide uncertainty presentation, the probability prediction methods
      (e.g., Gaussian process regression (GPR) and relevance vector machine (RVM)) are
      especially adaptable to perform anomaly detection for sensing series. Generally,
      one key parameter of prediction models is coverage probability (CP), which
      controls the judging threshold of the testing sample and is generally set to a
      default value (e.g., 90% or 95%). There are few criteria to determine the optimal
      CP for anomaly detection. Therefore, this paper designs a graphic indicator of
      the receiver operating characteristic curve of prediction interval (ROC-PI) based
      on the definition of the ROC curve which can depict the trade-off between the PI
      width and PI coverage probability across a series of cut-off points. Furthermore,
      the Youden index is modified to assess the performance of different CPs, by the
      minimization of which the optimal CP is derived by the simulated annealing (SA)
      algorithm. Experiments conducted on two simulation datasets demonstrate the
      validity of the proposed method. Especially, an actual case study on sensing
      series from an on-orbit satellite illustrates its significant performance in
      practical application.

PMID- 29587373
TI  - Analysis of Known Linear Distributed Average Consensus Algorithms on Cycles and
      Paths.
AB  - In this paper, we compare six known linear distributed average consensus
      algorithms on a sensor network in terms of convergence time (and therefore, in
      terms of the number of transmissions required). The selected network topologies
      for the analysis (comparison) are the cycle and the path. Specifically, in the
      present paper, we compute closed-form expressions for the convergence time of
      four known deterministic algorithms and closed-form bounds for the convergence
      time of two known randomized algorithms on cycles and paths. Moreover, we also
      compute a closed-form expression for the convergence time of the fastest
      deterministic algorithm considered on grids.

PMID- 29587374
TI  - Electrochemical Biosensors: A Solution to Pollution Detection with Reference to
      Environmental Contaminants.
AB  - The increasing environmental pollution with particular reference to emerging
      contaminants, toxic heavy elements, and other hazardous agents is a serious
      concern worldwide. Considering this global issue, there is an urgent need to
      design and develop strategic measuring techniques with higher efficacy and
      precision to detect a broader spectrum of numerous contaminants. The development
      of precise instruments can further help in real-time and in-process monitoring of
      the generation and release of environmental pollutants from different industrial
      sectors. Moreover, real-time monitoring can also reduce the excessive consumption
      of several harsh chemicals and reagents with an added advantage of on-site
      determination of contaminant composition prior to discharge into the environment.
      With key scientific advances, electrochemical biosensors have gained considerable
      attention to solve this problem. Electrochemical biosensors can be an excellent
      fit as an analytical tool for monitoring programs to implement legislation.
      Herein, we reviewed the current trends in the use of electrochemical biosensors
      as novel tools to detect various contaminant types including toxic heavy
      elements. A particular emphasis was given to screen-printed electrodes, nanowire
      sensors, and paper-based biosensors and their role in the pollution detection
      processes. Towards the end, the work is wrapped up with concluding remarks and
      future perspectives. In summary, electrochemical biosensors and related areas
      such as bioelectronics, and (bio)-nanotechnology seem to be growing areas that
      will have a marked influence on the development of new bio-sensing strategies in
      future studies.

PMID- 29587375
TI  - Coverage of Emotion Recognition for Common Wearable Biosensors.
AB  - The present research proposes a novel emotion recognition framework for the
      computer prediction of human emotions using common wearable biosensors. Emotional
      perception promotes specific patterns of biological responses in the human body,
      and this can be sensed and used to predict emotions using only biomedical
      measurements. Based on theoretical and empirical psychophysiological research,
      the foundation of autonomic specificity facilitates the establishment of a strong
      background for recognising human emotions using machine learning on physiological
      patterning. However, a systematic way of choosing the physiological data covering
      the elicited emotional responses for recognising the target emotions is not
      obvious. The current study demonstrates through experimental measurements the
      coverage of emotion recognition using common off-the-shelf wearable biosensors
      based on the synchronisation between audiovisual stimuli and the corresponding
      physiological responses. The work forms the basis of validating the hypothesis
      for emotional state recognition in the literature and presents coverage of the
      use of common wearable biosensors coupled with a novel preprocessing algorithm to
      demonstrate the practical prediction of the emotional states of wearers.

PMID- 29587376
TI  - Effect of Double Bond Position on 2-Phenyl-benzofuran Antioxidants: A Comparative
      Study of Moracin C and Iso-Moracin C.
AB  - Two 2-phenyl-benzofurans, moracin C {2-[3',5'-dihydroxy-4'-(3-methlbut-2
      enyl)phenyl]-6-hydroxybenzofuran} and its isomer iso-moracin C{2-[3',5'-dihydroxy
      4'-(3-methlbut-1-enyl)phenyl]-6-hydroxybenzofuran}, were comparatively studied
      using redox-related antioxidant assays and non-redox antioxidant assays. Moracin
      C always resulted in higher IC50 values than iso-moracin C in the redox-related
      antioxidant assays, including *O2--inhibition, Cu2+-reducing power, DPPH*
      inhibition, and ABTS+*-inhibition assays. In the non-redox antioxidant assay,
      moracin C and iso-moracin C underwent similar radical-adduct-formation (RAF),
      evidenced by the peaks at m/z 704 and m/z 618 in HPLC-MS spectra. In conclusion,
      both moracin C and iso-moracin C can act as 2-phenyl-benzofuran antioxidants;
      their antioxidant mechanisms may include redox-related ET and H+-transfer, and
      non-redox RAF. A double bond at the conjugation position can enhance the redox
      related antioxidant potential, but hardly affects the RAF potential.

PMID- 29587377
TI  - Groundsel Bush (Baccharis halimifolia) Extract Promotes Adipocyte Differentiation
      In Vitro and Increases Adiponectin Expression in Mature Adipocytes.
AB  - An ethanolic extract of Baccharis halimifolia (groundsel bush, GB), which is a
      native Louisiana plant with documented use in Creole folk medicine, has been
      shown to inhibit lipopolysaccharide (LPS)-induced inflammation in cultured
      macrophages. Here, we examine the effects of GB on adipocyte development and
      function, as these processes are attractive targets for intervention in insulin
      resistance. Oil Red O neutral lipid staining, reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR), and immunoblotting were used to measure GB
      effects on lipid accumulation, gene expression, and protein abundance,
      respectively. In differentiating 3T3-L1 adipocytes, GB enhanced lipid
      accumulation and increased expression of several adipogenic genes (GLUT4, aP2,
      ADPN, CEBPalpha, FAS, and PPARgamma). Protein levels of two of these adipogenic
      markers (aP2 and adiponectin) were examined and found to be induced by GB
      treatment. In mature adipocytes, GB reduced the gene expression of resistin, a
      pro-inflammatory endocrine factor, increased the adiponectin protein levels in a
      time-dependent manner, and substantially attenuated the TNF-alpha-induced
      reduction in adiponectin. In macrophages, GB reduced the expression of pro
      inflammatory genes that were induced by LPS. GB produces metabolically favorable
      changes in differentiating adipocytes, mature adipocytes, and macrophages in
      vitro, suggesting its potential use as a dietary supplement or nutraceutical to
      support metabolic health and resiliency.

PMID- 29587378
TI  - Green Grape Detection and Picking-Point Calculation in a Night-Time Natural
      Environment Using a Charge-Coupled Device (CCD) Vision Sensor with Artificial
      Illumination.
AB  - Night-time fruit-picking technology is important to picking robots. This paper
      proposes a method of night-time detection and picking-point positioning for green
      grape-picking robots to solve the difficult problem of green grape detection and
      picking in night-time conditions with artificial lighting systems. Taking a
      representative green grape named Centennial Seedless as the research object,
      daytime and night-time grape images were captured by a custom-designed visual
      system. Detection was conducted employing the following steps: (1) The RGB (red,
      green and blue). Color model was determined for night-time green grape detection
      through analysis of color features of grape images under daytime natural light
      and night-time artificial lighting. The R component of the RGB color model was
      rotated and the image resolution was compressed; (2) The improved Chan-Vese (C-V)
      level set model and morphological processing method were used to remove the
      background of the image, leaving out the grape fruit; (3) Based on the character
      of grape vertical suspension, combining the principle of the minimum
      circumscribed rectangle of fruit and the Hough straight line detection method,
      straight-line fitting for the fruit stem was conducted and the picking point was
      calculated using the stem with an angle of fitting line and vertical line less
      than 15 degrees . The visual detection experiment results showed that the
      accuracy of grape fruit detection was 91.67% and the average running time of the
      proposed algorithm was 0.46 s. The picking-point calculation experiment results
      showed that the highest accuracy for the picking-point calculation was 92.5%,
      while the lowest was 80%. The results demonstrate that the proposed method of
      night-time green grape detection and picking-point calculation can provide
      technical support to the grape-picking robots.

PMID- 29587380
TI  - A Novel Laser and Video-Based Displacement Transducer to Monitor Bridge
      Deflections.
AB  - The measurement of static vertical deflections on bridges continues to be a first
      level technological challenge. These data are of great interest, especially for
      the case of long-term bridge monitoring; in fact, they are perhaps more valuable
      than any other measurable parameter. This is because material degradation
      processes and changes of the mechanical properties of the structure due to aging
      (for example creep and shrinkage in concrete bridges) have a direct impact on the
      exhibited static vertical deflections. This paper introduces and evaluates an
      approach to monitor displacements and rotations of structures using a novel laser
      and video-based displacement transducer (LVBDT). The proposed system combines the
      use of laser beams, LED lights, and a digital video camera, and was especially
      designed to capture static and slow-varying displacements. Contrary to other
      video-based approaches, the camera is located on the bridge, hence allowing to
      capture displacements at one location. Subsequently, the sensing approach and the
      procedure to estimate displacements and the rotations are described.
      Additionally, laboratory and in-service field testing carried out to validate the
      system are presented and discussed. The results demonstrate that the proposed
      sensing approach is robust, accurate, and reliable, and also inexpensive, which
      are essential for field implementation.

PMID- 29587379
TI  - Galectin-3 in Atrial Fibrillation: Mechanisms and Therapeutic Implications.
AB  - Maintenance of atrial fibrillation is a complex mechanism, including extensive
      electrical and structural remodeling of the atria which involves progressive
      fibrogenesis. Galectin-3 is a biomarker of fibrosis, and, thus, may be involved
      in atrial remodeling in atrial fibrillation patients. We review the role of
      galectin-3 in AF mechanisms and its potential therapeutic implications.

PMID- 29587381
TI  - Influence of Algae Age and Population on the Response to TiO2 Nanoparticles.
AB  - This work shows the influence of algae age (at the time of the exposure) and the
      initial algae population on the response of green algae Raphidocelis subcapitata
      to titanium dioxide nanoparticles (TiO2 NPs). The different algae age was
      obtained by changes in flow rate of continually stirred tank reactors prior to NP
      exposure. Increased algae age led to a decreased growth, variations in
      chlorophyll content, and an increased lipid peroxidation. Increased initial algae
      population (0.3-4.2 * 106 cells/mL) at a constant NP concentration (100 mg/L)
      caused a decline in the growth of algae. With increased initial algae population,
      the lipid peroxidation and chlorophyll both initially decreased and then
      increased. Lipid peroxidation had 4* the amount of the control at high and low
      initial population but, at mid-ranged initial population, had approximately half
      the control value. Chlorophyll a results also showed a similar trend. These
      results indicate that the physiological state of the algae is important for the
      toxicological effect of TiO2 NPs. The condition of algae and exposure regime must
      be considered in detail when assessing the toxicological response of NPs to
      algae.

PMID- 29587382
TI  - Functional Characterization of Novel Atrial Fibrillation-Linked GJA5 (Cx40)
      Mutants.
AB  - Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Recently,
      four novel heterozygous Cx40 mutations-K107R, L223M, Q236H, and I257L-were
      identified in 4 of 310 unrelated AF patients and a followup genetic analysis of
      the mutant carriers' families showed that the mutants were present in all the
      affected members. To study possible alterations associated with these Cx40
      mutants, including their cellular localization and gap junction (GJ) function, we
      expressed GFP-tagged and untagged mutants in connexin-deficient model cells. All
      four Cx40 mutants showed clustered localization at cell-cell junctions similar to
      that observed of wildtype Cx40. However, cell pairs expressing Cx40 Q236H, but
      not the other individual mutants, displayed a significantly lower GJ coupling
      conductance (Gj) than wildtype Cx40. Similarly, co-expression of Cx40 Q236H with
      Cx43 resulted in a significantly lower Gj. Transjunctional voltage-dependent
      gating (Vj gating) properties were also altered in the GJs formed by Q236H.
      Reduced GJ function and altered Vj gating may play a role in promoting the Q236H
      carriers to AF.

PMID- 29587383
TI  - Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to
      Human Papillomavirus (HPV) and Clinical Outcome.
AB  - Human papillomavirus (HPV) is a major etiological factor for tonsillar and the
      base of tongue cancer (TSCC/BOTSCC). HPV-positive and HPV-negative TSCC/BOTSCC
      present major differences in mutations, mRNA expression and clinical outcome.
      Earlier protein studies on TSCC/BOTSCC have mainly analyzed individual proteins.
      Here, the aim was to compare a larger set of cancer and immune related proteins
      in HPV-positive and HPV-negative TSCC/BOTSCC in relation to normal tissue,
      presence of HPV, and clinical outcome. Fresh frozen tissue from 42 HPV-positive
      and 17 HPV-negative TSCC/BOTSCC, and corresponding normal samples, were analyzed
      for expression of 167 proteins using two Olink multiplex immunoassays. Major
      differences in protein expression between TSCC/BOTSCC and normal tissue were
      identified, especially in chemo- and cytokines. Moreover, 34 proteins, mainly
      immunoregulatory proteins and chemokines, were differently expressed in HPV
      positive vs HPV-negative TSCC/BOTSCC. Several proteins were potentially related
      to clinical outcome for HPV-positive or HPV-negative tumors. For HPV-positive
      tumors, these were mostly related to angiogenesis and hypoxia. Correlation with
      clinical outcome of one of these, VEGFA, was validated by immunohistochemistry.
      Differences in immune related proteins between HPV-positive and HPV-negative
      TSCC/BOTSCC reflect the stronger activity of the immune defense in the former.
      Angiogenesis related proteins might serve as potential targets for therapy in HPV
      positive TSCC/BOTSCC.

PMID- 29587384
TI  - High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of
      Survival and Apoptosis in Endothelial Cells.
AB  - Diabetes and hyperglycemia are associated with increased retinal oxidative and
      nitrative stress and vascular cell death. Paradoxically, high glucose stimulates
      expression of survival and angiogenic growth factors. Therefore, we examined the
      hypothesis that high glucose-mediated tyrosine nitration causes inhibition of the
      survival protein PI3-kinase, and in particular, its regulatory p85 subunit in
      retinal endothelial cell (EC) cultures. Retinal EC were cultured in high glucose
      (HG, 25 mM) for 3 days or peroxynitrite (PN, 100 uM) overnight in the presence or
      absence of a peroxynitrite decomposition catalyst (FeTPPs, 2.5 uM), or the
      selective nitration inhibitor epicatechin (100 uM). Apoptosis of ECs was assessed
      using TUNEL assay and caspase-3 activity. Immunoprecipitation and Western blot
      were used to assess protein expression and tyrosine nitration of p85 subunit and
      its interaction with the p110 subunit. HG or PN accelerated apoptosis of retinal
      ECs compared to normal glucose (NG, 5 mM) controls. HG- or PN-treated cells also
      showed significant increases in tyrosine nitration on the p85 subunit of PI3
      kinase that inhibited its association with the catalytic p110 subunit and
      impaired PI3-kinase/Akt kinase activity. Decomposing peroxynitrite or blocking
      tyrosine nitration of p85 restored the activity of PI3-kinase, and prevented
      apoptosis and activation of p38 MAPK. Inhibiting p38 MAPK or overexpression of
      the constitutively activated Myr-Akt construct prevented HG- or peroxynitrite
      mediated apoptosis. In conclusion, HG impairs pro-survival signals and causes
      accelerated EC apoptosis, at least in part via tyrosine nitration and inhibition
      of PI3-kinase. Inhibitors of nitration can be used in adjuvant therapy to delay
      diabetic retinopathy and microvascular complication.

PMID- 29587385
TI  - Label-Free Electrochemical Detection of Vanillin through Low-Defect Graphene
      Electrodes Modified with Au Nanoparticles.
AB  - Graphene is an excellent modifier for the surface modification of electrochemical
      electrodes due to its exceptional physical properties and, for the development of
      graphene-based chemical and biosensors, is usually coated on glassy carbon
      electrodes (GCEs) via drop casting. However, the ease of aggregation and high
      defect content of reduced graphene oxides degrade the electrical properties.
      Here, we fabricated low-defect graphene electrodes by catalytically thermal
      treatment of HPHT diamond substrate, followed by the electrodeposition of Au
      nanoparticles (AuNPs) with an average size of ~60 nm on the electrode surface
      using cyclic voltammetry. The Au nanoparticle-decorated graphene electrodes show
      a wide linear response range to vanillin from 0.2 to 40 uM with a low limit of
      detection of 10 nM. This work demonstrates the potential applications of graphene
      based hybrid electrodes for highly sensitive chemical detection.

PMID- 29587387
TI  - Thylakoid-Deposited Micro-Pillar Electrodes for Enhanced Direct Extraction of
      Photosynthetic Electrons.
AB  - Photosynthesis converts solar energy to electricity in a highly efficient manner.
      Since only water is needed as fuel for energy conversion, this highly efficient
      energy conversion process has been rigorously investigated. In particular,
      photosynthetic apparatus, such as photosystem II (PSII), photosystem I (PSI), or
      thylakoids, have been isolated from various plants to construct bio-hybrid
      anodes. Although PSII or PSI decorated anodes have shown potentials, there still
      remain challenges, such as poor stability of PSII-based systems or need for
      electron donors other than water molecules of PSI-based systems. Thylakoid
      membranes are relatively stable after isolation and they contain all the
      necessary photosynthetic apparatus including the PSII and PSI. To increase
      electrical connections between thylakoids and anodes, nanomaterials such as
      carbon nanotubes, nanowires, nanoparticles, or graphene have been employed.
      However, since they rely on the secondary electrical connections between
      thylakoids and anodes; it is desired to achieve larger direct contacts between
      them. Here, we aimed to develop micro-pillar (MP) array anodes to maximize direct
      contact with thylakoids. The thylakoid morphology was analyzed and the MP array
      was designed to maximize direct contact with thylakoids. The performance of MP
      anodes and a photosynthetic fuel cell based on MP electrodes was demonstrated and
      analyzed.

PMID- 29587386
TI  - Co2 and Co3 Mixed Cluster Secondary Building Unit Approach toward a Three
      Dimensional Metal-Organic Framework with Permanent Porosity.
AB  - Large and permanent porosity is the primary concern when designing metal-organic
      frameworks (MOFs) for specific applications, such as catalysis and drug delivery.
      In this article, we report a MOF Co11(BTB)6(NO3)4(DEF)2(H2O)14 (1, H3BTB = 1,3,5
      tris(4-carboxyphenyl)benzene; DEF = N,N-diethylformamide) via a mixed cluster
      secondary building unit (SBU) approach. MOF 1 is sustained by a rare combination
      of a linear trinuclear Co3 and two types of dinuclear Co2 SBUs in a 1:2:2 ratio.
      These SBUs are bridged by BTB ligands to yield a three-dimensional (3D) non
      interpenetrated MOF as a result of the less effective packing due to the
      geometrically contrasting SBUs. The guest-free framework of 1 has an estimated
      density of 0.469 g cm-3 and exhibits a potential solvent accessible void of 69.6%
      of the total cell volume. The activated sample of 1 exhibits an estimated
      Brunauer-Emmett-Teller (BET) surface area of 155 m2 g-1 and is capable of CO2
      uptake of 58.61 cm3 g-1 (2.63 mmol g-1, 11.6 wt % at standard temperature and
      pressure) in a reversible manner at 195 K, showcasing its permanent porosity.

PMID- 29587388
TI  - Liquid Phase Plasma Synthesis of Iron Oxide Nanoparticles on Nitrogen-Doped
      Activated Carbon Resulting in Nanocomposite for Supercapacitor Applications.
AB  - Iron oxide nanoparticles supported on nitrogen-doped activated carbon powder were
      synthesized using an innovative plasma-in-liquid method, called the liquid phase
      plasma (LPP) method. Nitrogen-doped carbon (NC) was prepared by a primary LPP
      reaction using an ammonium chloride reactant solution, and an iron oxide/NC
      composite (IONCC) was prepared by a secondary LPP reaction using an iron chloride
      reactant solution. The nitrogen component at 3.77 at. % formed uniformly over the
      activated carbon (AC) surface after a 1 h LPP reaction. Iron oxide nanoparticles,
      40~100 nm in size, were impregnated homogeneously over the NC surface after the
      LPP reaction, and were identified as Fe3O4 by X-ray photoelectron spectroscopy
      and X-ray diffraction. NC and IONCCs exhibited pseudo-capacitive characteristics,
      and their specific capacitance and cycling stability were superior to those of
      bare AC. The nitrogen content on the NC surface increased the compatibility and
      charge transfer rate, and the composites containing iron oxide exhibited a lower
      equivalent series resistance.

PMID- 29587389
TI  - Lynch Syndrome-Related Clear Cell Carcinoma of the Cervix: A Case Report.
AB  - Lynch syndrome, a hereditary cancer syndrome, occurs because of germline
      mutations in at least one of four DNA mismatch repair genes (MutL Homolog 1
      (MLH1), MutS Homolog 2 (MSH2), MutS Homolog 6 (MSH6), and PMS1 Homolog 2 (PMS2)).
      The disorder is associated with colorectal, endometrial, and other epithelial
      malignancies, but not cervical cancer. We report a woman with Lynch syndrome with
      synchronous cervical cancer. This is the first report of Lynch syndrome-related
      clear cell carcinoma of the cervix, which indicates the possibility of an
      association between cervical cancer and Lynch syndrome. Suitable genetic tests
      are required to determine whether common genetics can account for synchronous or
      subsequent malignancies in Lynch syndrome patients and their families. Such
      knowledge will also enhance our understanding of the genetic mechanisms governing
      the development of apparently unrelated cancers.

PMID- 29587390
TI  - Sedentary Behaviour and Hair Cortisol Amongst Women Living in Socioeconomically
      Disadvantaged Neighbourhoods: A Cross-Sectional Study.
AB  - Women living in socioeconomically disadvantaged neighbourhoods are at heightened
      risk of experiencing psychological stress. Therefore, identifying potential risk
      factors for stress is important to support positive mental health. A growing body
      of research has linked sedentary behaviour with mental ill-health (e.g.,
      depression and anxiety); however, little research has specifically investigated
      potential linkages between sedentary behaviour and stress. Therefore, the aim of
      this study was to investigate the association between common types of sedentary
      behaviour and objectively-measured stress (as measured by hair cortisol levels)
      amongst women living in socioeconomically disadvantaged neighbourhoods. During
      2012-2013, 72 women (aged 18-46 years) living in socioeconomically disadvantaged
      neighbourhoods self-reported sedentary behaviour (TV viewing, computer use,
      overall sitting time) and provided hair samples. Hair cortisol levels were
      measured using enzyme-linked immunosorbent assay. Linear regression models
      examined cross-sectional associations between sedentary behaviour and hair
      cortisol levels. There was no association between any type of sedentary behaviour
      (TV viewing, computer use, or overall sitting time) and hair cortisol levels in
      either crude or adjusted models. Sedentary behaviour may not be linked to hair
      cortisol level (stress) in women living in socioeconomically disadvantaged
      neighbourhoods. Further studies utilising objective measures of both sedentary
      behaviour and stress are required to confirm these findings.

PMID- 29587391
TI  - Nondestructive Estimation of Muscle Contributions to STS Training with Different
      Loadings Based on Wearable Sensor System.
AB  - Partial body weight support or loading sit-to-stand (STS) rehabilitation can be
      useful for persons with lower limb dysfunction to achieve movement again based on
      the internal residual muscle force and external assistance. To explicate how the
      muscles contribute to the kinetics and kinematics of STS performance by non
      invasive in vitro detection and to nondestructively estimate the muscle
      contributions to STS training with different loadings, a wearable sensor system
      was developed with ground reaction force (GRF) platforms, motion capture inertial
      sensors and electromyography (EMG) sensors. To estimate the internal moments of
      hip, knee and ankle joints and quantify the contributions of individual muscle
      and gravity to STS movement, the inverse dynamics analysis on a simplified STS
      biomechanical model with external loading is proposed. The functional roles of
      the lower limb individual muscles (rectus femoris (RF), gluteus maximus (GM),
      vastus lateralis (VL), tibialis anterior (TA) and gastrocnemius (GAST)) during
      STS motion and the mechanism of the muscles' synergies to perform STS-specific
      subtasks were analyzed. The muscle contributions to the biomechanical STS
      subtasks of vertical propulsion, anteroposterior (AP) braking and propulsion for
      body balance in the sagittal plane were quantified by experimental studies with
      EMG, kinematic and kinetic data.

PMID- 29587392
TI  - Correction of Visual Perception Based on Neuro-Fuzzy Learning for the Humanoid
      Robot TEO.
AB  - New applications related to robotic manipulation or transportation tasks, with or
      without physical grasping, are continuously being developed. To perform these
      activities, the robot takes advantage of different kinds of perceptions. One of
      the key perceptions in robotics is vision. However, some problems related to
      image processing makes the application of visual information within robot control
      algorithms difficult. Camera-based systems have inherent errors that affect the
      quality and reliability of the information obtained. The need of correcting image
      distortion slows down image parameter computing, which decreases performance of
      control algorithms. In this paper, a new approach to correcting several sources
      of visual distortions on images in only one computing step is proposed. The goal
      of this system/algorithm is the computation of the tilt angle of an object
      transported by a robot, minimizing image inherent errors and increasing computing
      speed. After capturing the image, the computer system extracts the angle using a
      Fuzzy filter that corrects at the same time all possible distortions, obtaining
      the real angle in only one processing step. This filter has been developed by the
      means of Neuro-Fuzzy learning techniques, using datasets with information
      obtained from real experiments. In this way, the computing time has been
      decreased and the performance of the application has been improved. The resulting
      algorithm has been tried out experimentally in robot transportation tasks in the
      humanoid robot TEO (Task Environment Operator) from the University Carlos III of
      Madrid.

PMID- 29587393
TI  - Roma Housing and Eating in 1775 and 2013: A Comparison.
AB  - We compared housing and the eating habits of Roma. Contemporary findings (2013)
      were compared with those from the first monothematic work on Roma (1775), which
      depicts their housing and eating habits, especially regarding the differences
      between social classes. Data were obtained from a journal (1775) and from semi
      structured interviews (2013) with more than 70 Roma women and men who live in
      segregated and excluded settlements at the edges of villages or scattered among
      the majority. Data were collected in two villages and one district town in the
      Tatra region, where the data from the 1775 measurements originated. We used
      classical sociological theory to interpret the obtained data. The main findings
      showed differences between specific social classes then and now regarding
      housing, as well as the eating habits related to both conditions among the Roma
      in the Tatra region. The houses of rich Roma families did not differ from the
      houses of the majority population. The huts of the poorest inhabitants of
      settlements did not meet any hygiene standards. Typical Roma foods such as goja
      or marikla were the traditional foods of Slovak peasants living in poverty in the
      country. We concluded that the housing and eating habits of the citizens of poor
      settlements located in the eastern parts of Slovakia are still similar to those
      of two centuries ago. The existing social exclusion may be explained partly from
      this finding.

PMID- 29587394
TI  - Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2
      (Alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones.
AB  - In this study, a novel series of 4-(2-(alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro
      3H-1,2,4-triazol-3-ones (4a-m) was designed and synthesized. The anticonvulsant
      activities of these compounds were evaluated by using the maximal electroshock
      seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice.
      The neurotoxicity of these compounds was evaluated using the rotarod
      neurotoxicity test. The majority of compounds showed anti-MES activities at 100
      or 300 mg/kg. Compound 4g was considered to be the most promising, based on its
      potency against MES- and PTZ-induced seizures with ED50 values of 23.7 and 18.9
      mg/kg, respectively. The TD50 value of 4g was 284.0 mg/kg, which resulted in a
      higher protective index (PI = TD50/ED50) value than that of carbamazepine and
      valproate. In an ELISA test, compound 4g significantly increased the gamma
      aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with
      thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly
      decreased the activity of 4g in the MES model, which suggests that the mechanism
      through which compound 4g elicits its anticonvulsive action is at least in part
      through increasing the GABA level in the brain.

PMID- 29587395
TI  - Long-Time Relaxation of Stress-Induced Birefringence of Microcrystalline Alkali
      Halide Crystals.
AB  - Alkali halide single crystals are most commonly used as the diluent matrix in the
      tablet method or disk technique for spectroscopic measurements. However, stress
      induced birefringence (SIB) of alkali halides as well as intrinsic birefringence
      manifest during the disk formation process. Thus, the true chiroptical
      measurement is disturbed by optical anisotropies (OA) containing SIB and
      intrinsic birefringence, except in the case of optical homogeneity. SIB is
      generally larger than intrinsic birefringence and has a value of several thousand
      millidegrees in the ultraviolet-visible wavelength range, although this varies
      with disk type. Here, to investigate the SIB origin, alkali halide crystals were
      examined using polarized light, X-ray diffraction, Fourier-transform infrared,
      and electron backscattering diffraction spectroscopic measurements. It was found
      that, after stress release, the SIB exhibited nonlinear long-time relaxation,
      which roughly converged within several hours, with the only time-invariant
      intrinsic birefringence remaining being due to OA. This behavior was strongly
      related to an increase in the quasi-amorphous domain and the generation of an air
      gap between the crystallite boundaries and their pellets. Further, a
      straightforward correlation was found between amorphization and an increase in
      the disk water content caused by deliquescence. Thus, the OA of alkali halide
      single crystals was found to have two different origins yielding intrinsic
      birefringence and SIB.

PMID- 29587396
TI  - A Portable Wireless Communication Platform Based on a Multi-Material Fiber Sensor
      for Real-Time Breath Detection.
AB  - In this paper, we present a new mobile wireless communication platform for real
      time monitoring of an individual's breathing rate. The platform takes the form of
      a wearable stretching T-shirt featuring a sensor and a detection base station.
      The sensor is formed by a spiral-shaped antenna made from a multi-material fiber
      connected to a compact transmitter. Based on the resonance frequency of the
      antenna at approximately 2.4 GHz, the breathing sensor relies on its Bluetooth
      transmitter. The contactless and non-invasive sensor is designed without
      compromising the user's comfort. The sensing mechanism of the system is based on
      the detection of the signal amplitude transmitted wirelessly by the sensor, which
      is found to be sensitive to strain. We demonstrate the capability of the platform
      to detect the breathing rates of four male volunteers who are not in movement.
      The breathing pattern is obtained through the received signal strength indicator
      (RSSI) which is filtered and analyzed with home-made algorithms in the portable
      system. Numerical simulations of human breath are performed to support the
      experimental detection, and both results are in a good agreement. Slow, fast,
      regular, irregular, and shallow breathing types are successfully recorded within
      a frequency interval of 0.16-1.2 Hz, leading to a breathing rate varying from 10
      to 72 breaths per minute.

PMID- 29587398
TI  - Concentrations of 2,4-Dichlorophenol and 2,5-Dichlorophenol in Urine of Korean
      Adults.
AB  - Humans are exposed to the environmental pollutants 2,4-dichlorophenol (2,4-DCP)
      and 2,5-dichlorophenol (2,5-DCP) through air, the use of water and the
      consumption of products. In this study, we evaluated the urinary concentrations
      of these compounds in Korean people between the ages of 18 to 69 years, by making
      use of data from the Korean National Human Biomonitoring Survey that was
      completed in 2009. Of 1865 representative Koreans, 63.4% and 97.9% were found to
      have concentrations of 2,4-DCP and 2,5-DCP > 0.05 MUg/L (limit of detection) in
      their urine, respectively. The geometric mean of urinary concentrations was 0.14
      MUg/L (confidence interval of 95% = 0.13-0.16) and 0.44 MUg/L (confidence
      interval = 0.41-0.48), respectively. It was found that the adjusted proportional
      changes in 2,4-DCP concentrations were significantly associated with body mass
      index, whereas those of 2,5-DCP concentrations were influenced by place of
      residence. From these findings, it is evident that most adults in Korea have
      levels of 2,4-DCP and 2,5-DCP that are detectable in their urine and the burden
      of these compounds on their bodies varies depending on numerous demographic
      factors.

PMID- 29587397
TI  - Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a
      Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure
      Targeting Long Alpha Helix of Hemagglutinin.
AB  - To overcome yearly efforts and costs for the production of seasonal influenza
      vaccines, new approaches for the induction of broadly protective and long-lasting
      immune responses have been developed in the past decade. To warrant safety and
      efficacy of the emerging crossreactive vaccine candidates, it is critical to
      understand the evolution of influenza viruses in response to these new immune
      pressures. Here we applied unique molecular identifiers in next generation
      sequencing to analyze the evolution of influenza quasispecies under in vivo
      antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our
      vaccine targeting LAH of hemagglutinin elicited significant seroconversion and
      protection against homologous and heterologous influenza virus strains in mice.
      The vaccine not only significantly reduced lung viral titers, but also induced a
      well-known bottleneck effect by decreasing virus diversity. In contrast to the
      classical bottleneck effect, here we showed a significant increase in the
      frequency of viruses with amino acid sequences identical to that of vaccine
      targeting LAH domain. No escape mutant emerged after vaccination. These results
      not only support the potential of a universal influenza vaccine targeting the
      conserved LAH domains, but also clearly demonstrate that the well-established
      bottleneck effect on viral quasispecies evolution does not necessarily generate
      escape mutants.

PMID- 29587399
TI  - An Indoor Positioning-Based Mobile Payment System Using Bluetooth Low Energy
      Technology.
AB  - The development of information technology has paved the way for faster and more
      convenient payment process flows and new methodology for the design and
      implementation of next generation payment systems. The growth of smartphone usage
      nowadays has fostered a new and popular mobile payment environment. Most of the
      current generation smartphones support Bluetooth Low Energy (BLE) technology to
      communicate with nearby BLE-enabled devices. It is plausible to construct an Over
      the-Air BLE-based mobile payment system as one of the payment methods for people
      living in modern societies. In this paper, a secure indoor positioning-based
      mobile payment authentication protocol with BLE technology and the corresponding
      mobile payment system design are proposed. The proposed protocol consists of
      three phases: initialization phase, session key construction phase, and
      authentication phase. When a customer moves toward the POS counter area, the
      proposed mobile payment system will automatically detect the position of the
      customer to confirm whether the customer is ready for the checkout process. Once
      the system has identified the customer is standing within the payment-enabled
      area, the payment system will invoke authentication process between POS and the
      customer's smartphone through BLE communication channel to generate a secure
      session key and establish an authenticated communication session to perform the
      payment transaction accordingly. A prototype is implemented to assess the
      performance of the proposed design for mobile payment system. In addition,
      security analysis is conducted to evaluate the security strength of the proposed
      protocol.

PMID- 29587400
TI  - Association between Cervical Spondylosis and Migraine: A Nationwide Retrospective
      Cohort Study.
AB  - Background: Few studies have investigated the longitudinal association between
      cervical spondylosis (CS) and migraine by using a nationwide population-based
      database. Methods: We conducted a retrospective cohort study from 2000 to 2011
      identifying 27,930 cases of cervical spondylosis and 111,720 control subjects
      (those without cervical spondylosis) from a single database. The subjects were
      frequency-matched on the basis of sex, age, and diagnosis date. The non- cervical
      spondylosis cohort was four times the size of the cervical spondylosis cohort. To
      quantify the effects of cervical spondylosis on the risk of migraine, univariate
      and multivariate Cox proportional hazard regression analyses were used to
      calculate the hazard ratio (HR), and 95% confidence interval (CI). Results: After
      a 10-year follow-up controlling for potential confounding factors, overall
      migraine incidence was higher in the cervical spondylosis cohort than in the non
      cervical spondylosis cohort (5.16 and 2.09 per 1000 people per year,
      respectively; crude hazard ratio = 2.48, 95% confidence interval = 2.28-2.69),
      with an adjusted hazard ratio of 2.03 (95% confidence interval = 1.86-2.22) after
      accounting for sex, age, comorbidities, and medication. Individuals with
      myelopathy in the cervical spondylosis cohort had a 2.19 times (95% confidence
      interval = 1.80-2.66) higher incidence of migraine when compared than did those
      in the non- cervical spondylosis cohort. Conclusions: Individuals with cervical
      spondylosis exhibited a higher risk of migraine than those without cervical
      spondylosis. The migraine incidence rate was even higher among individuals with
      cervical spondylotic myelopathy.

PMID- 29587402
TI  - Understanding Outdoor Gyms in Public Open Spaces: A Systematic Review and
      Integrative Synthesis of Qualitative and Quantitative Evidence.
AB  - (1) Background: An outdoor gym (OG) is environmental infrastructure built in a
      public open space to promote structured physical activity. The provision of OGs
      is increasingly seen as an important strategy to realize public health agendas
      promoting habitual physical activity. A systematic review was conducted to
      synthesize characteristics of OG and OG users' experiences and perceptions in
      different cultural contexts; (2) Methods: Online searches of multidisciplinary
      databases were conducted in health, sport and recreation, and urban planning
      disciplines. Characteristics of OGs were synthesized by integrating evidence from
      quantitative, qualitative, and mix-methods studies. The experiences and
      perceptions of OG users from both qualitative data and survey responses were
      synthesized through framework analysis; (3) Results: Nine studies met the
      inclusion criteria (three quantitative studies, four mixed-methods studies, and
      two pure qualitative studies). None were excluded on the basis of quality. OGs
      mainly serve adult and older adult population groups. Their size, design, and
      instructional support vary across studies. The inclusion of functional types of
      equipment did not have a unified standard. Regarding experiences and perceptions
      of OGs, five major themes emerged: "health", "social connectedness",
      "affordable", "support", and "design and promotion"; (4) Conclusions: The OG
      characteristics synthesis guides the direction in further studies regarding
      exploration of design parameters. The qualitative and quantitative synthesis
      revealed that health was a central theme of users' experiences. OGs are also
      spaces where community-dwellers can find social connectedness while participating
      in structured physical activity at no cost. Findings from this review create
      knowledge support for OG as environmental infrastructure for further research and
      facilitate the understanding of users' experiences and perceptions of OGs in
      different cultural contexts.

PMID- 29587401
TI  - Inactivation of SREBP-1a Phosphorylation Prevents Fatty Liver Disease in Mice:
      Identification of Related Signaling Pathways by Gene Expression Profiles in Liver
      and Proteomes of Peroxisomes.
AB  - The key lipid metabolism transcription factor sterol regulatory element-binding
      protein (SREBP)-1a integrates gene regulatory effects of hormones, cytokines,
      nutrition and metabolites as lipids, glucose, or cholesterol via phosphorylation
      by different mitogen activated protein kinase (MAPK) cascades. We have previously
      reported the impact of SREBP-1a phosphorylation on the phenotype in transgenic
      mouse models with liver-specific overexpression of the N-terminal transcriptional
      active domain of SREBP-1a (alb-SREBP-1a) or a MAPK phosphorylation site-deficient
      variant (alb-SREBP-1a?P; (S63A, S117A, T426V)), respectively. In this report, we
      investigated the molecular basis of the systemic observations by holistic
      analyses of gene expression in liver and of proteome patterns in lipid-degrading
      organelles involved in the pathogenesis of metabolic syndrome, i.e., peroxisomes,
      using 2D-DIGE and mass spectrometry. The differences in hepatic gene expression
      and peroxisomal protein patterns were surprisingly small between the control and
      alb-SREBP-1a mice, although the latter develop a severe phenotype with visceral
      obesity and fatty liver. In contrast, phosphorylation site-deficient alb-SREBP
      1a?P mice, which are protected from fatty liver disease, showed marked
      differences in hepatic gene expression and peroxisomal proteome patterns. Further
      knowledge-based analyses revealed that disruption of SREBP-1a phosphorylation
      resulted in massive alteration of cellular processes, including signs for loss of
      targeting lipid pathways.

PMID- 29587403
TI  - Non-Invasive Methodology to Estimate Polyphenol Content in Extra Virgin Olive Oil
      Based on Stepwise Multilinear Regression.
AB  - Normally the olive oil quality is assessed by chemical analysis according to
      international standards. These norms define chemical and organoleptic markers,
      and depending on the markers, the olive oil can be labelled as lampante, virgin,
      or extra virgin olive oil (EVOO), the last being an indicator of top quality. The
      polyphenol content is related to EVOO organoleptic features, and different
      scientific works have studied the positive influence that these compounds have on
      human health. The works carried out in this paper are focused on studying
      relations between the polyphenol content in olive oil samples and its spectral
      response in the near infrared spectra. In this context, several acquisition
      parameters have been assessed to optimize the measurement process within the
      virgin olive oil production process. The best regression model reached a mean
      error value of 156.14 mg/kg in leave one out cross validation, and the higher
      regression coefficient was 0.81 through holdout validation.

PMID- 29587404
TI  - Identification of Dysregulated microRNA Networks in Schwann Cell-Like Cultures
      Exposed to Immune Challenge: Potential Crosstalk with the Protective VIP/PACAP
      Neuropeptide System.
AB  - Following peripheral nerve injury, dysregulations of certain non-coding microRNAs
      (miRNAs) occur in Schwann cells. Whether these alterations are the result of
      local inflammation and/or correlate with perturbations in the expression profile
      of the protective vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase
      activating polypeptide (PACAP) system is currently unknown. To address these
      issues, we aimed at profiling the expression of selected miRNAs in the rat RT4
      Schwann cell line. Cells exposed to lipopolysaccharide (LPS), to mimic the local
      inflammatory milieu, were appraised by real-time qPCR, Western blot and ELISAs.
      We found that upon LPS treatment, levels of pro-inflammatory cytokines (IL-1beta,
      -6, -18, -17A, MCP-1 and TNFalpha) increased in a time-dependent manner.
      Unexpectedly, the expression levels of VIP and PACAP were also increased.
      Conversely, levels of VPAC1 and VPAC2 receptors were reduced. Downregulated
      miRNAs included miR-181b, -145, -27a, -340 and -132 whereas upregulated ones were
      miR-21, -206, -146a, -34a, -155, -204 and -29a, respectively. Regression analyses
      revealed that a subset of the identified miRNAs inversely correlated with the
      expression of VPAC1 and VPAC2 receptors. In conclusion, these findings identified
      a novel subset of miRNAs that are dysregulated by immune challenge whose
      activities might elicit a regulatory function on the VIP/PACAP system.

PMID- 29587405
TI  - Further New Diterpenoids as PTP1B Inhibitors from the Xisha Soft Coral Sinularia
      polydactyla.
AB  - A new prenyleudesmane type diterpene, sinupol (8), and a new capnosane type
      diterpenoid, sinulacetate (9), were isolated from the Xisha soft coral Sinularia
      polydactyla along with five known related diterpenes (4-7 and 10). Their
      structures, including absolute configurations, were determined by extensive
      spectroscopic analysis, the comparison of their NMR data with those of related
      compounds, and time-dependent density functional theory electronic circular
      dichroism (TDDFT ECD) calculations. Both new compounds (8 and 9) exhibited
      promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a
      potential drug target for the treatment of type II diabetes and obesity.

PMID- 29587406
TI  - Characterization of Phenolic Compounds in Wine Lees.
AB  - The effect of vinification techniques on phenolic compounds and antioxidant
      activity of wine lees are poorly understood. The present study investigated the
      antioxidant activity of white and red wine lees generated at early fermentation
      and during aging. In this study, the total phenol content (TPC), total tannin
      content (TTC), mean degree of polymerization (mDP), and antioxidant activities of
      five white and eight red wine lees samples from different vinification
      backgrounds were determined. The results showed that vinification techniques had
      a significant (p < 0.05) impact on total phenol and tannin content of the
      samples. White wine lees had high mDP content compared with red ones. Catechin
      (50-62%) and epicatechin contents were the predominant terminal units of
      polymeric proanthocyanidin extracted from examined samples. Epigallocatechin was
      the predominant extension unit of white wine lees, whereas epicatechin was the
      predominant compound in red wine marc. The ORAC (oxygen radical absorbance
      capacity) assay was strongly correlated with the DPPH (alpha, alpha-diphenyl-beta
      picrylhydrazyl) assay, and the results showed the strong antioxidant activities
      associated with red wine lees (PN > 35 mg Trolox/g FDM) (PN: Pinot noir lees;
      FDM: Freeze-dried Material). This study indicates that tannin is one of the major
      phenolic compounds available in wine lees that can be useful in human and animal
      health applications.

PMID- 29587407
TI  - Ultra-Long-Distance Hybrid BOTDA/F-OTDR.
AB  - In the distributed optical fiber sensing (DOFS) domain, simultaneous measurement
      of vibration and temperature/strain based on Rayleigh scattering and Brillouin
      scattering in fiber could have wide applications. However, there are certain
      challenges for the case of ultra-long sensing range, including the interplay of
      different scattering mechanisms, the interaction of two types of sensing signals,
      and the competition of pump power. In this paper, a hybrid DOFS system, which can
      simultaneously measure temperature/strain and vibration over 150 km, is
      elaborately designed via integrating the Brillouin optical time-domain analyzer
      (BOTDA) and phase-sensitive optical time-domain reflectometry (F-OTDR).
      Distributed Raman and Brillouin amplifications, frequency division multiplexing
      (FDM), wavelength division multiplexing (WDM), and time division multiplexing
      (TDM) are delicately fused to accommodate ultra-long-distance BOTDA and F-OTDR.
      Consequently, the sensing range of the hybrid system is 150.62 km, and the
      spatial resolution of BOTDA and F-OTDR are 9 m and 30 m, respectively. The
      measurement uncertainty of the BOTDA is +/- 0.82 MHz. To the best of our
      knowledge, this is the first time that such hybrid DOFS is realized with a
      hundred-kilometer length scale.

PMID- 29587408
TI  - Trauma and Depression among North Korean Refugees: The Mediating Effect of
      Negative Cognition.
AB  - North Korean refugees experience adaptation difficulties, along with a wide range
      of psychological problems. Accordingly, this study examined the associations
      between early traumatic experiences, negative automatic thoughts, and depression
      among young North Korean refugees living in South Korea. Specifically, we
      examined how different factors of negative automatic thoughts would mediate the
      relationship between early trauma and depressive symptoms. A total of 109 North
      Korean refugees aged 13-29 years were recruited from two alternative schools. Our
      path analysis indicated that early trauma was positively linked with thoughts of
      personal failure, physical threat, and hostility, but not with thoughts of social
      threat. The link with depressive symptoms was only significant for thoughts of
      personal failure. After removing all non-significant pathways, the model revealed
      that early traumatic experiences were positively associated with depressive
      symptoms (beta = 0.61, 95% CI = 0.48-0.73) via thoughts of personal failure (beta
      = 0.17, 95% CI = 0.08-0.28), as well as directly (beta = 0.44, 95% CI = 0.27
      0.59). Interventions that target negative cognitions of personal failure may be
      helpful for North Korean refugees at risk of depression.

PMID- 29587410
TI  - Osteogenic Potential of Pre-Osteoblastic Cells on a Chitosan-graft
      Polycaprolactone Copolymer.
AB  - A chitosan-graft-polycaprolactone (CS-g-PCL) copolymer synthesized via a multi
      step process was evaluated as a potential biomaterial for the adhesion and growth
      of MC3T3-E1 pre-osteoblastic cells. A strong adhesion of the MC3T3-E1 cells with
      a characteristic spindle-shaped morphology was observed from the first days of
      cell culture onto the copolymer surfaces. The viability and proliferation of the
      cells on the CS-g-PCL surfaces, after 3 and 7 days in culture, were significantly
      higher compared to the cells cultured on the tissue culture treated polystyrene
      (TCPS) control. The osteogenic potential of the pre-osteoblastic cells cultured
      on CS-g-PCL surfaces was evaluated by determining various osteogenic
      differentiation markers and was compared to the TCPS control surface.
      Specifically, alkaline phosphatase activity levels show significantly higher
      values at both time points compared to TCPS, while secreted collagen into the
      extracellular matrix was found to be higher on day 7. Calcium biomineralization
      deposited into the matrix is significantly higher for the CS-g-PCL copolymer
      after 14 days in culture, while the levels of intracellular osteopontin were
      significantly higher on the CS-g-PCL surfaces compared to TCPS. The enhanced
      osteogenic response of the MC3T3-E1 pre-osteoblasts cultured on CS-g-PCL reveals
      that the copolymer underpins the cell functions towards bone tissue formation and
      is thus an attractive candidate for use in bone tissue engineering.

PMID- 29587409
TI  - Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?
AB  - Although several viruses can easily infect the central nervous system (CNS),
      antiviral drugs often show dramatic difficulties in penetrating the brain from
      the bloodstream since they are substrates of active efflux transporters (AETs).
      These transporters, located in the physiological barriers between blood and the
      CNS and in macrophage membranes, are able to recognize their substrates and
      actively efflux them into the bloodstream. The active transporters currently
      known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1),
      multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or
      MRP5), and breast cancer resistance protein (ABCG2 or BCRP). Inhibitors of AETs
      may be considered, but their co-administration causes serious unwanted effects.
      Nasal administration of antiviral drugs is therefore proposed in order to
      overcome the aforementioned problems, but innovative devices, formulations
      (thermoreversible gels, polymeric micro- and nano-particles, solid lipid
      microparticles, nanoemulsions), absorption enhancers (chitosan, papaverine), and
      mucoadhesive agents (chitosan, polyvinilpyrrolidone) are required in order to
      selectively target the antiviral drugs and, possibly, the AET inhibitors in the
      CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the
      AET systems, appearing as interesting substrates for innovative nasal
      formulations able to target anti-Human Immunodeficiency Virus (HIV) agents into
      macrophages of the CNS, which are one of the most important HIV Sanctuaries of
      the body.

PMID- 29587411
TI  - Relationship between Response to PDE5 Inhibitors and Penile Duplex Doppler
      Ultrasound in Erectile Dysfunction.
AB  - The relationship between the results of penile duplex Doppler ultrasound (PDDU)
      and response to vardenafil was investigated in patients diagnosed with erectile
      dysfunction (ED). Data from 148 patients with ED were analyzed retrospectively.
      Patients who did not respond to therapy were classified in to Group I (n = 32),
      those who responded partially were classified into Group II (n = 40), and
      complete responders were classified into Group III (n = 76). Age, comorbidities,
      and vascular and penile pathologies were compared among the three groups. While
      diabetes mellitus (DM) and dyslipidemia positivity adversely affected the
      response to treatment, the presence of hypertension (HT), Peyronie's disease and
      priapism increased the therapeutic response to the treatment (p < 0.05). Arterial
      insufficiency was present in 20 (30.3%), 25 (37.9%) and 21 (31.8%) of the
      patients in Group I, Group II and Group III, respectively (p = 0.001). Venous
      insufficiency was observed in three (14.3%) patients in Group I and in eight
      (85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen
      in 9 (30%), 14 (46.7%) and 7 (23.3%) of the patients in Group I, Group II and
      Group III, respectively (p = 0.001). The response rate to treatment was highest
      in normal patients according to PDDU, followed by patients with venous
      insufficiency. In addition, it was found that DM decreased the response to
      treatment, whereas the response increased in cases with HT, priapism and
      Peyronie's disease.

PMID- 29587412
TI  - Epidemiological Studies to Support the Development of Next Generation Influenza
      Vaccines.
AB  - The National Institute of Allergy and Infectious Diseases recently published a
      strategic plan for the development of a universal influenza vaccine. This plan
      focuses on improving understanding of influenza infection, the development of
      influenza immunity, and rational design of new vaccines. Epidemiological studies
      such as prospective, longitudinal cohort studies are essential to the completion
      of these objectives. In this review, we discuss the contributions of
      epidemiological studies to our current knowledge of vaccines and correlates of
      immunity, and how they can contribute to the development and evaluation of the
      next generation of influenza vaccines. These studies have been critical in
      monitoring the effectiveness of current influenza vaccines, identifying issues
      such as low vaccine effectiveness, reduced effectiveness among those who receive
      repeated vaccination, and issues related to egg adaptation during the
      manufacturing process. Epidemiological studies have also identified population
      level correlates of protection that can inform the design and development of next
      generation influenza vaccines. Going forward, there is an enduring need for
      epidemiological studies to continue advancing knowledge of correlates of
      protection and the development of immunity, to evaluate and monitor the
      effectiveness of next generation influenza vaccines, and to inform
      recommendations for their use.

PMID- 29587414
TI  - Identification of Blueberry miRNAs and Their Targets Based on High-Throughput
      Sequencing and Degradome Analyses.
AB  - miRNAs are important regulators of plant gene expression. To better characterize
      their functions, we applied high-throughput sequencing and degradome analyses to
      investigate three blueberry (Vaccinium ashei) tissues. A total of 127 known and
      101 novel miRNAs were identified. Moreover, 141 targets for 42 known and 19 novel
      miRNAs were experimentally validated by degradome sequencing. A functional
      analysis of these miRNA targets revealed they were associated with diverse
      biological activities and several pathways, e.g., anthocyanin biosynthesis and
      cytokinin signal transduction. The data presented herein expand our understanding
      of the regulation of blueberry miRNAs during floral and fruit development stages.
      They may also provide new insights into the roles of miRNAs during anthocyanin
      biosynthesis in blueberry fruits.

PMID- 29587413
TI  - Multifaced Roles of the alphavbeta3 Integrin in Ehlers-Danlos and Arterial
      Tortuosity Syndromes' Dermal Fibroblasts.
AB  - The alphavbeta3 integrin, an endothelial cells' receptor-binding fibronectin (FN)
      in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling
      during migration, invasion, angiogenesis, wound healing and inflammation, and is
      also involved in the epithelial mesenchymal transition. In vitro-grown human
      control fibroblasts organize a fibrillar network of FN, which is preferentially
      bound on the entire cell surface to its canonical alpha5beta1 integrin receptor,
      whereas the alphavbeta3 integrin is present only in rare patches in focal
      contacts. We report on the preferential recruitment of the alphavbeta3 integrin,
      due to the lack of FN-ECM and its canonical integrin receptor, in dermal
      fibroblasts from Ehlers-Danlos syndromes (EDS) and arterial tortuosity syndrome
      (ATS), which are rare multisystem connective tissue disorders. We review our
      previous findings that unraveled different biological mechanisms elicited by the
      alphavbeta3 integrin in fibroblasts derived from patients affected with classical
      (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders
      (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type
      III collagens, alphavbeta3 rescues patients' fibroblasts from anoikis through a
      paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD,
      without a defined molecular basis, the alphavbeta3 integrin transduces to the ILK
      Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the
      deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox
      imbalance, ECM disarray together with the activation of a non-canonical
      alphavbeta3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The
      characterization of these different biological functions triggered by alphavbeta3
      provides insights into the multifaced nature of this integrin, at least in
      cultured dermal fibroblasts, offering future perspectives for research in this
      field.

PMID- 29587416
TI  - Knocking down Insulin Receptor in Pancreatic Beta Cell lines with Lentiviral
      Small Hairpin RNA Reduces Glucose-Stimulated Insulin Secretion via Decreasing the
      Gene Expression of Insulin, GLUT2 and Pdx1.
AB  - Type 2 diabetes (T2D) is a metabolic disorder characterized by beta cell
      dysfunction and insulin resistance in fat, muscle and liver cells. Recent studies
      have shown that the development of insulin resistance in pancreatic beta cell
      lines may contribute to beta cell dysfunction in T2D. However, there still is a
      lack of detailed investigations regarding the mechanisms by which insulin
      deficiency may contribute in diabetes. In this study, we firstly established a
      stable insulin receptor knockdown cell line in pancreatic beta cells INS-1
      (InsRbetaKD cells) using anti InsRbeta small hairpin RNA (InsRbeta-shRNA) encoded
      by lentiviral vectors. The resultant InsRbetaKD cells demonstrated a
      significantly reduced expression of InsRbeta as determined by real-time PCR and
      Western blotting analyses. Upon removing glucose from the medium, these cells
      exhibited a significant decrease in insulin gene expression and protein secretion
      in response to 20 mM glucose stimulation. In accordance with this insulin
      reduction, the glucose uptake efficiency as indicated by a 3[H]-2-deoxy-d-glucose
      assay also decreased. Furthermore, InsRbetaKD cells showed a dramatic decrease in
      glucose transporter 2 (GLUT2, encoded by SLC2A2) and pancreatic duodenal homeobox
      (Pdx1) mRNA expression compared to the controls. These data collectively suggest
      that pancreatic beta cell insulin resistance contributes to the development of
      beta cell dysfunction by impairing pancreatic beta cell glucose sensation through
      the Pdx1- GLUT2 pathway. InsRbetaKD cells provide a good model to further
      investigate the mechanism of beta-cell dysfunction in T2D.

PMID- 29587417
TI  - Role of the Hypothalamic-Pituitary-Adrenal Axis in Health and Disease.
AB  - The Hypothalamic-Pituitary-adrenal (HPA) axis describes a complex set of positive
      and negative feedback influences between the hypothalamus, pituitary gland, and
      adrenal gland.[...].

PMID- 29587415
TI  - The Sealing Zone in Osteoclasts: A Self-Organized Structure on the Bone.
AB  - Osteoclasts form a specialized cell-matrix adhesion structure, known as the
      "sealing zone", during bone resorption. The sealing zone is a dynamic actin-rich
      structure that defines the resorption area of the bone. The detailed dynamics and
      fine structure of the sealing zone have been elusive. Osteoclasts plated on glass
      do not form a sealing zone, but generate a separate supra-molecular structure
      called the "podosome belt". Podosomes are integrin-based adhesion complexes
      involved in matrix adhesion, cell migration, matrix degradation, and
      mechanosensing. Invadopodia, podosome-like protrusions in cancer cells, are
      involved in cell invasion into other tissues by promoting matrix degradation.
      Both podosomes and invadopodia exhibit actin pattern transitions during
      maturation. We previously found that Arp2/3-dependent actin flow occurs in all
      observed assembly patterns of podosomes in osteoclasts on glass. It is known that
      the actin wave in Dictyostelium cells exhibits a similar pattern transition in
      its evolution. Because of significant advances in our understanding regarding the
      mechanism of podosomes/invadopodia formation over the last decade, we revisited
      the structure and function of the sealing zone in this review, highlighting the
      possible involvement of self-organized actin waves in the organogenesis of the
      sealing zone.

PMID- 29587418
TI  - Genome-Wide Identification, Expression, and Functional Analysis of the Sugar
      Transporter Gene Family in Cassava (Manihot esculenta).
AB  - The sugar transporter (STP) gene family encodes monosaccharide transporters that
      contain 12 transmembrane domains and belong to the major facilitator superfamily.
      STP genes play critical roles in monosaccharide distribution and participate in
      diverse plant metabolic processes. To investigate the potential roles of STPs in
      cassava (Manihot esculenta) tuber root growth, genome-wide identification and
      expression and functional analyses of the STP gene family were performed in this
      study. A total of 20 MeSTP genes (MeSTP1-20) containing the Sugar_tr conserved
      motifs were identified from the cassava genome, which could be further classified
      into four distinct groups in the phylogenetic tree. The expression profiles of
      the MeSTP genes explored using RNA-seq data showed that most of the MeSTP genes
      exhibited tissue-specific expression, and 15 out of 20 MeSTP genes were mainly
      expressed in the early storage root of cassava. qRT-PCR analysis further
      confirmed that most of the MeSTPs displayed higher expression in roots after 30
      and 40 days of growth, suggesting that these genes may be involved in the early
      growth of tuber roots. Although all the MeSTP proteins exhibited plasma membrane
      localization, variations in monosaccharide transport activity were found through
      a complementation analysis in a yeast (Saccharomyces cerevisiae) mutant,
      defective in monosaccharide uptake. Among them, MeSTP2, MeSTP15, and MeSTP19 were
      able to efficiently complement the uptake of five monosaccharides in the yeast
      mutant, while MeSTP3 and MeSTP16 only grew on medium containing galactose,
      suggesting that these two MeSTP proteins are transporters specific for galactose.
      This study provides significant insights into the potential functions of MeSTPs
      in early tuber root growth, which possibly involves the regulation of
      monosaccharide distribution.

PMID- 29587419
TI  - Enhanced Sensitivity to Subphonemic Segments in Dyslexia: A New Instance of
      Allophonic Perception.
AB  - Although dyslexia can be individuated in many different ways, it has only three
      discernable sources: a visual deficit that affects the perception of letters, a
      phonological deficit that affects the perception of speech sounds, and an audio
      visual deficit that disturbs the association of letters with speech sounds.
      However, the very nature of each of these core deficits remains debatable. The
      phonological deficit in dyslexia, which is generally attributed to a deficit of
      phonological awareness, might result from a specific mode of speech perception
      characterized by the use of allophonic (i.e., subphonemic) units. Here we will
      summarize the available evidence and present new data in support of the
      "allophonic theory" of dyslexia. Previous studies have shown that the dyslexia
      deficit in the categorical perception of phonemic features (e.g., the voicing
      contrast between /t/ and /d/) is due to the enhanced sensitivity to allophonic
      features (e.g., the difference between two variants of /d/). Another consequence
      of allophonic perception is that it should also give rise to an enhanced
      sensitivity to allophonic segments, such as those that take place within a
      consonant cluster. This latter prediction is validated by the data presented in
      this paper.

PMID- 29587420
TI  - Photophysical and Photocatalytic Properties of BiSnSbO6 under Visible Light
      Irradiation.
AB  - BiSnSbO6 with strong photocatalytic activity was first fabricated by a high
      temperature, solid-state sintering method. The resulting BiSnSbO6 was
      characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD), UV-vis diffuse reflectance
      spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). The results showed
      that BiSnSbO6, with a pyrochlore structure and a cubic crystal system by a space
      group Fd3m, was well crystallized. The lattice parameter or the band gap of
      BiSnSbO6 was 10.234594 A or 2.83 eV. Compared with N-doped TiO2, BiSnSbO6 showed
      higher photocatalytic activity in the degradation of benzotriazole and rhodamine
      B. The apparent first-order rate constant for BiSnSbO6 in the degradation of
      benzotriazole and rhodamine B was 0.0182 min-1 and 0.0147 min-1, respectively. On
      the basis of the scavenger experiment, during the photocatalytic process, the
      main active species were arranged in order of increasing photodegradation rate:
      *OH < *O2- < h+. The removal rate of benzotriazole or rhodamine B was
      approximately estimated to be 100% with BiSnSbO6 as a photocatalyst after 200 min
      visible-light irradiation. Plentiful CO2 produced by the experiment indicated
      that benzotriazole or rhodamine B was continuously mineralized during the
      photocatalytic process. Finally, the possible photodegradation pathways of
      benzotriazole and rhodamine B were deduced.

PMID- 29587421
TI  - Synthesis and Characterization of Highly Sensitive Hydrogen (H2) Sensing Device
      Based on Ag Doped SnO2 Nanospheres.
AB  - In this paper, pure and Ag-doped SnO2 nanospheres were synthesized by
      hydrothermal method and characterized via X-ray powder diffraction (XRD), field
      emission scanning electron microscopy (FESEM), energy dispersive spectroscopy
      (EDS), and X-ray photoelectron spectra (XPS), respectively. The gas sensing
      performance of the pure, 1 at.%, 3 at.%, and 5 at.% Ag-doped SnO2 sensing devices
      toward hydrogen (H2) were systematically evaluated. The results indicated that
      compared with pure SnO2 nanospheres, Ag-doped SnO2 nanospheres could not only
      decrease the optimum working temperature but also significantly improve H2
      sensing such as higher gas response and faster response-recovery. Among all the
      samples, the 3 at.% Ag-doped SnO2 showed the highest response 39 to 100 MUL/L H2
      at 300  degrees C. Moreover, its gas sensing mechanism was discussed, and the
      results will provide reference and theoretical guidance for the development of
      high-performance SnO2-based H2 sensing devices.

PMID- 29587422
TI  - Curing Effects on Interfacial Adhesion between Recycled Carbon Fiber and Epoxy
      Resin Heated by Microwave Irradiation.
AB  - The interfacial adhesion of recycled carbon fiber (CF) reinforced epoxy composite
      heated by microwave (MW) irradiation were investigated by changing the curing
      state of the epoxy resin. The recycled CF was recovered from the composite, which
      was prepared by vacuum-assisted resin transfer molding, by thermal degradation at
      500 or 600  degrees C. Thermogravimetric analysis showed that the heating at 600 
      degrees C caused rough damage to the CF surface, whereas recycled CF recovered at
      500  degrees C have few defects. The interfacial shear strength (IFSS) between
      recycled CF and epoxy resin was measured by a single-fiber fragmentation test.
      The test specimen was heated by MW after mixing the epoxy resin with a curing
      agent or pre-curing, in order to investigate the curing effects on the matrix
      resin. The IFSSs of the MW-irradiated samples were significantly varied by the
      curing state of the epoxy resin and the surface condition of recycled CF,
      resulting that they were 99.5 to 131.7% of oven heated samples Furthermore,
      rheological measurements showed that the viscosity and shrinking behaviors of
      epoxy resin were affected based on the curing state of epoxy resin before MW
      irradiation.

PMID- 29587423
TI  - Iodine and Pregnancy-A Qualitative Study Focusing on Dietary Guidance and
      Information.
AB  - Iodine is essential for thyroid hormones synthesis and normal neurodevelopment;
      however, ~60% of pregnant women do not meet the WHO (World Health Organization)
      recommended intake. Using a qualitative design, we explored the perceptions,
      awareness, and experiences of pregnancy nutrition, focusing on iodine. Women in
      the perinatal period (n = 48) were interviewed and filled in a food frequency
      questionnaire for iodine. Almost all participants achieved the recommended 150
      MUg/day intake for non-pregnant adults (99%), but only 81% met the increased
      demands of pregnancy (250 MUg/day). Most were unaware of the importance, sources
      of iodine, and recommendations for iodine intake. Attitudes toward dairy products
      consumption were positive (e.g., helps with heartburn; easy to increase).
      Increased fish consumption was considered less achievable, with barriers around
      taste, smell, heartburn, and morning sickness. Community midwives were the main
      recognised provider of dietary advice. The dietary advice received focused most
      often on multivitamin supplements rather than food sources. Analysis highlighted
      a clear theme of commitment to change behaviour, motivated by pregnancy, with a
      desired focus on user-friendly documentation and continued involvement of the
      health services. The study highlights the importance of redirecting advice on
      dietary requirements in pregnancy and offers practical suggestions from women in
      the perinatal period as the main stakeholder group.

PMID- 29587424
TI  - Multi-Aperture-Based Probabilistic Noise Reduction of Random Telegraph Signal
      Noise and Photon Shot Noise in Semi-Photon-Counting Complementary-Metal-Oxide
      Semiconductor Image Sensor.
AB  - A probabilistic method to remove the random telegraph signal (RTS) noise and to
      increase the signal level is proposed, and was verified by simulation based on
      measured real sensor noise. Although semi-photon-counting-level (SPCL) ultra-low
      noise complementary-metal-oxide-semiconductor (CMOS) image sensors (CISs) with
      high conversion gain pixels have emerged, they still suffer from huge RTS noise,
      which is inherent to the CISs. The proposed method utilizes a multi-aperture (MA)
      camera that is composed of multiple sets of an SPCL CIS and a moderately fast and
      compact imaging lens to emulate a very fast single lens. Due to the redundancy of
      the MA camera, the RTS noise is removed by the maximum likelihood estimation
      where noise characteristics are modeled by the probability density distribution.
      In the proposed method, the photon shot noise is also relatively reduced because
      of the averaging effect, where the pixel values of all the multiple apertures are
      considered. An extremely low-light condition that the maximum number of electrons
      per aperture was the only 2 e - was simulated. PSNRs of a test image for simple
      averaging, selective averaging (our previous method), and the proposed method
      were 11.92 dB, 11.61 dB, and 13.14 dB, respectively. The selective averaging,
      which can remove RTS noise, was worse than the simple averaging because it
      ignores the pixels with RTS noise and photon shot noise was less improved. The
      simulation results showed that the proposed method provided the best noise
      reduction performance.

PMID- 29587425
TI  - Radiofrequency Electromagnetic Radiation and Memory Performance: Sources of
      Uncertainty in Epidemiological Cohort Studies.
AB  - Uncertainty in experimental studies of exposure to radiation from mobile phones
      has in the past only been framed within the context of statistical variability.
      It is now becoming more apparent to researchers that epistemic or reducible
      uncertainties can also affect the total error in results. These uncertainties are
      derived from a wide range of sources including human error, such as data
      transcription, model structure, measurement and linguistic errors in
      communication. The issue of epistemic uncertainty is reviewed and interpreted in
      the context of the MoRPhEUS, ExPOSURE and HERMES cohort studies which investigate
      the effect of radiofrequency electromagnetic radiation from mobile phones on
      memory performance. Research into this field has found inconsistent results due
      to limitations from a range of epistemic sources. Potential analytic approaches
      are suggested based on quantification of epistemic error using Monte Carlo
      simulation. It is recommended that future studies investigating the relationship
      between radiofrequency electromagnetic radiation and memory performance pay more
      attention to treatment of epistemic uncertainties as well as further research
      into improving exposure assessment. Use of directed acyclic graphs is also
      encouraged to display the assumed covariate relationship.

PMID- 29587426
TI  - Exploring Geographic Variation of Mental Health Risk and Service Utilization of
      Doctors and Hospitals in Toronto: A Shared Component Spatial Modeling Approach.
AB  - Mental Health has been known to vary geographically. Different rates of
      utilization of mental health services in local areas reflect geographic variation
      of mental health and complexity of health care. Variations and inequalities in
      how the health care system addresses risks are two critical issues for addressing
      population mental health. This study examines these issues by analyzing the
      utilization of mental health services in Toronto at the neighbourhood level. We
      adopted a shared component spatial modeling approach that allows simultaneous
      analysis of two main health service utilizations: doctor visits and
      hospitalizations related to mental health conditions. Our results reflect a
      geographic variation of both types of mental health service utilization across
      neighbourhoods in Toronto. We identified hot and cold spots of mental health
      risks that are common to both or specific to only one type of health service
      utilization. Based on the evidence found, we discuss intervention strategies,
      focusing on the hotspots and provision of health services about doctors and
      hospitals, to improve mental health for the neighbourhoods. Limitations of the
      study and further research directions are also discussed.

PMID- 29587427
TI  - Surface Modification of Ti-35Nb-10Ta-1.5Fe by the Double Acid-Etching Process.
AB  - Surface topography and composition influence the osteoblastic proliferation and
      osseointegration rates, which favor the biomechanical stability of bone anchoring
      and implants. In recent years, beta titanium alloys have been developed, and are
      composed of biocompatible elements, have low elastic modulus, high corrosion
      resistance, and mechanical properties to improve the long performance behavior of
      biomaterials. In the present research, the influence of the acid-etching process
      was studied in Ti6Al4V ELI and Ti35Nb10Ta1.5Fe. Samples were etched in a two-step
      acid treatment. Surface roughness parameters were quantified under a confocal
      microscope, topography was studied by scanning electron microscopy, and surface
      composition was analyzed with energy dispersive X-ray spectroscopy. The results
      revealed that the two-step acid treatment changes the topography of the beta
      alloy, increases the surface area, and changes the chemical composition of the
      surface. Two differentiated regions were identified in the Ti35Nb10Ta1.5Fe alloy
      after the acid-etching process: The alpha + beta region with higher values of
      mean roughness due to the lower chemical resistance of this region; and the beta
      region with lower values of roughness parameters.

PMID- 29587430
TI  - Structure and Chemical Bonding of the Li-Doped Polar Intermetallic RE2In1-xLixGe2
      (RE = La, Nd, Sm, Gd; x = 0.13, 0.28, 0.43, 0.53) System.
AB  - Four polar intermetallic compounds belonging to the RE2In1-xLixGe2 (RE = La, Nd,
      Sm, Gd; x = 0.13(1), 0.28(1), 0.43(1), 0.53(1)) system have been synthesized by
      the traditional solid-state reaction method, and their crystal structures have
      been characterized by single-crystal X-ray diffraction (SXRD) analyses. The
      isotypic crystal structures of four title compounds adopt the Mo2FeB2-type
      structure having the tetragonal space group P4/mbm (Z = 2, Pearson code tP40)
      with three crystallographically independent atomic sites and can be simply
      described as a pile of the identical 2-dimensioanl (2D) RE2In1-xLixGe2 slabs
      stacked along the c-axis direction. The substituting Li atom shows a particular
      site preference for replacing In at the Wyckoff 2a site rather than Ge at the
      Wyckoff 4g in this crystal structure. As the size of a used rare-earth metal
      decreases from La3+ to Gd3+ throughout the title system, the Ge-Ge and Ge-In/Li
      bond distances, both of which consist of the 2D anionic Ge2(In/Li) layer,
      gradually decrease resulting in the reduction of a unit cell volume. A series of
      theoretical investigations has been performed using a hypothetical structure
      model Gd2In0.5Li0.5Ge2 by tight-binding linear muffin-tin orbital (TB-LMTO)
      method. The resultant densities of states (DOS) value at the Fermi level (EF)
      suggests a metallic conductivity for this particular composition, and this
      calculation result is in a good agreement with the formal charge distribution
      assigning two extra valence electrons for a metal-metal bond in the conduction
      band. The thorough analyses of six crystal orbital Hamilton population (COHP)
      curves representing various interatomic interactions and an electron localization
      function (ELF) diagram indicating the locations of paired-electron densities are
      also provided in this article.

PMID- 29587431
TI  - UHPLC-MS/MS Quantification Combined with Chemometrics for Comparative Analysis of
      Different Batches of Raw, Wine-Processed, and Salt-Processed Radix Achyranthis
      Bidentatae.
AB  - An accurate and reliable method using ultra-high performance liquid
      chromatography combined with triple quadrupole tandem mass spectrometry (UHPLC
      MS/MS) was established for simultaneous quantification of five major bioactive
      analytes in raw, wine-processed, and salt-processed Radix Achyranthis bidentatae
      (RAB). The results showed that this method exhibited desirable sensitivity,
      precision, stability, and repeatability. The overall intra-day and inter-day
      variations (RSD) were in the range of 1.57-2.46 and 1.51-3.00%, respectively. The
      overall recoveries were 98.58-101.48% with a relative standard deviation (RSD) of
      0.01-1.86%. In addition, the developed approach was applied to 21 batches of raw,
      wine-processed, and salt-processed samples of RAB. Hierarchical clustering
      analysis (HCA), principal component analysis (PCA), heat map, and boxplot
      analysis were performed to evaluate the quality of raw, wine-processed, and salt
      processed RAB collected from different regions. The chemometrics combined with
      the quantitative analysis based on UHPLC-MS/MS results indicated that the content
      of five analytes increased significantly in processed RAB compared to raw RAB.

PMID- 29587429
TI  - Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and
      Its Aglycone, Genipin.
AB  - For centuries, plants have been exploited by mankind as sources of numerous
      cancer chemotherapeutic agents. Good examples of anticancer compounds of clinical
      significance today include the taxanes (e.g., taxol), vincristine, vinblastine,
      and the podophyllotoxin analogues that all trace their origin to higher plants.
      While all these drugs, along with the various other available therapeutic
      options, brought some relief in cancer management, a real breakthrough or cure
      has not yet been achieved. This critical review is a reflection on the lessons
      learnt from decades of research on the iridoid glycoside geniposide and its
      aglycone, genipin, which are currently used as gold standard reference compounds
      in cancer studies. Their effects on tumour development (carcinogenesis), cancer
      cell survival, and death, with particular emphasis on their mechanisms of
      actions, are discussed. Particular attention is also given to mechanisms related
      to the dual pro-oxidant and antioxidant effects of these compounds, the
      mitochondrial mechanism of cancer cell killing through reactive oxygen species
      (ROS), including that generated through the uncoupling protein-2 (UCP-2), the
      inflammatory mechanism, and cell cycle regulation. The implications of various
      studies for the evaluation of glycosidic and aglycone forms of natural products
      in vitro and in vivo through pharmacokinetic scrutiny are also addressed.

PMID- 29587428
TI  - NF-kappaB Activation in Lymphoid Malignancies: Genetics, Signaling, and Targeted
      Therapy.
AB  - The NF-kappaB transcription factor family plays a crucial role in lymphocyte
      proliferation and survival. Consequently, aberrant NF-kappaB activation has been
      described in a variety of lymphoid malignancies, including diffuse large B-cell
      lymphoma, Hodgkin lymphoma, and adult T-cell leukemia. Several factors, such as
      persistent infections (e.g., with Helicobacter pylori), the pro-inflammatory
      microenvironment of the cancer, self-reactive immune receptors as well as genetic
      lesions altering the function of key signaling effectors, contribute to
      constitutive NF-kappaB activity in these malignancies. In this review, we will
      discuss the molecular consequences of recurrent genetic lesions affecting key
      regulators of NF-kappaB signaling. We will particularly focus on the oncogenic
      mechanisms by which these alterations drive deregulated NF-kappaB activity and
      thus promote the growth and survival of the malignant cells. As the concept of a
      targeted therapy based on the mutational status of the malignancy has been
      supported by several recent preclinical and clinical studies, further insight in
      the function of NF-kappaB modulators and in the molecular mechanisms governing
      aberrant NF-kappaB activation observed in lymphoid malignancies might lead to the
      development of additional treatment strategies and thus improve lymphoma therapy.

PMID- 29587432
TI  - Classification Accuracy of a Wearable Activity Tracker for Assessing Sedentary
      Behavior and Physical Activity in 3-5-Year-Old Children.
AB  - This study examined the accuracy of the Fitbit activity tracker (FF) for
      quantifying sedentary behavior (SB) and varying intensities of physical activity
      (PA) in 3-5-year-old children. Twenty-eight healthy preschool-aged children
      (Girls: 46%, Mean age: 4.8 +/- 1.0 years) wore the FF and were directly observed
      while performing a set of various unstructured and structured free-living
      activities from sedentary to vigorous intensity. The classification accuracy of
      the FF for measuring SB, light PA (LPA), moderate-to-vigorous PA (MVPA), and
      total PA (TPA) was examined calculating Pearson correlation coefficients (r),
      mean absolute percent error (MAPE), Cohen's kappa (k), sensitivity (Se),
      specificity (Sp), and area under the receiver operating curve (ROC-AUC). The
      classification accuracies of the FF (ROC-AUC) were 0.92, 0.63, 0.77 and 0.92 for
      SB, LPA, MVPA and TPA, respectively. Similarly, values of kappa, Se, Sp and
      percentage of correct classification were consistently high for SB and TPA, but
      low for LPA and MVPA. The FF demonstrated excellent classification accuracy for
      assessing SB and TPA, but lower accuracy for classifying LPA and MVPA. Our
      findings suggest that the FF should be considered as a valid instrument for
      assessing time spent sedentary and overall physical activity in preschool-aged
      children.

PMID- 29587433
TI  - What Persons with Chronic Health Conditions Need to Maintain or Return to Work
      Results of an Online-Survey in Seven European Countries.
AB  - Chronic health conditions represent the major share of the disease burden in
      Europe and have a significant impact on work. This study aims to: (1) identify
      factors that have a negative or positive impact on the work lives of persons with
      chronic health conditions; (2) explore the needs of these persons to maintain a
      job or return to work and (3) compare these results with respect to these
      persons' occupational status. An online survey was performed in seven European
      countries. Open-ended survey questions were analyzed using qualitative methods.
      In total, 487 participants with six chronic health conditions participated. The
      majority of participants named work-related aspects (such as career development,
      stress at the workplace, work structure and schedule as well as workload),
      support of others and attitudes of others as being the factors positively and
      negatively impact their work lives the most. Our study shed light on the
      importance of changing the attitudes of supervisors and co-workers to counteract
      stigmatization of persons with chronic health conditions in the workplace. In
      conclusion, this study provides a basis for developing new strategies of
      integration and reintegration at work for persons with chronic health conditions
      in European countries.

PMID- 29587434
TI  - Qualitative and Quantitative Analysis of Polyphenols in Lamiaceae Plants-A
      Review.
AB  - Lamiaceae species are promising potential sources of natural antioxidants, owing
      to their high polyphenol content. In addition, increasing scientific and
      epidemiological evidence have associated consumption of foods rich in polyphenols
      with health benefits such as decreased risk of cardiovascular diseases mediated
      through anti-inflammatory effects. The complex and diverse nature of polyphenols
      and the huge variation in their levels in commonly consumed herbs make their
      analysis challenging. Innovative robust analytical tools are constantly
      developing to meet these challenges. In this review, we present advances in the
      state of the art for the identification and quantification of polyphenols in
      Lamiaceae species. Novel chromatographic techniques that have been employed in
      the past decades are discussed, ranging from ultra-high-pressure liquid
      chromatography to hyphenated spectroscopic methods, whereas performance
      characteristics such as selectivity and specificity are also summarized.

PMID- 29587435
TI  - Non-Pleiotropic Coupling of Daily and Seasonal Temporal Isolation in the European
      Corn Borer.
AB  - Speciation often involves the coupling of multiple isolating barriers to produce
      reproductive isolation, but how coupling is generated among different premating
      barriers is unknown. We measure the degree of coupling between the daily mating
      time and seasonal mating time between strains of European corn borer (Ostrinia
      nubilalis) and evaluate the hypothesis that the coupling of different forms of
      allochrony is due to a shared genetic architecture, involving genes with
      pleiotropic effects on both timing phenotypes. We measure differences in gene
      expression at peak mating times and compare these genes to previously identified
      candidates that are associated with changes in seasonal mating time between the
      corn borer strains. We find that the E strain, which mates earlier in the season,
      also mates 2.7 h earlier in the night than the Z strain. Earlier daily mating is
      correlated with the differences in expression of the circadian clock genes cycle,
      slimb, and vrille. However, different circadian clock genes associate with daily
      and seasonal timing, suggesting that the coupling of timing traits is maintained
      by natural selection rather than pleiotropy. Juvenile hormone gene expression was
      associated with both types of timing, suggesting that circadian genes activate
      common downstream modules that may impose constraint on future evolution of these
      traits.

PMID- 29587437
TI  - Research on Strong Clutter Suppression for Gaofen-3 Dual-Channel SAR/GMTI.
AB  - In spaceborne synthetic aperture radar (SAR), moving targets are almost buried in
      ground clutter due to the wide clutter Doppler spectrum and the restricted pulse
      repetition frequency (PRF), which increases the difficulty of moving target
      detection. Clutter suppression is one of the key issues in the spaceborne SAR
      moving target indicator operation. In this paper, we describe the clutter
      suppression principle and analyze the influence of amplitude and phase error on
      clutter suppression. In the following, a novel dual-channel SAR clutter
      suppression algorithm is proposed, which is suitable for the Gaofen-3(GF-3) SAR
      sensor. The proposed algorithm consists of three technique steps, namely adaptive
      two-dimensional (2D) channel calibration, refined amplitude error correction and
      refined phase error correction. After channel error is corrected by these
      procedures, the clutter component, especially a strong clutter component, can be
      well suppressed. The validity of the proposed algorithm is verified by GF-3 SAR
      real data which demonstrates the ground moving-target indication (GMTI)
      capability of GF-3 SAR sensor.

PMID- 29587436
TI  - Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza
      Vaccine.
AB  - Next-generation vaccines that utilize T cells could potentially overcome the
      limitations of current influenza vaccines that rely on antibodies to provide
      narrow subtype-specific protection and are prone to antigenic mismatch with
      circulating strains. Evidence from animal models shows that T cells can provide
      heterosubtypic protection and are crucial for immune control of influenza virus
      infections. This has provided hope for the design of a universal vaccine able to
      prime against diverse influenza virus strains and subtypes. However, multiple
      hurdles exist for the realisation of a universal T cell vaccine. Overall primary
      concerns are: extrapolating human clinical studies, seeding durable effective T
      cell resident memory (Trm), population human leucocyte antigen (HLA) coverage,
      and the potential for T cell-mediated immune escape. Further comprehensive human
      clinical data is needed during natural infection to validate the protective role
      T cells play during infection in the absence of antibodies. Furthermore,
      fundamental questions still exist regarding the site, longevity and duration,
      quantity, and phenotype of T cells needed for optimal protection. Standardised
      experimental methods, and eventually simplified commercial assays, to assess
      peripheral influenza-specific T cell responses are needed for larger-scale
      clinical studies of T cells as a correlate of protection against influenza
      infection. The design and implementation of a T cell-inducing vaccine will
      require a consensus on the level of protection acceptable in the community, which
      may not provide sterilizing immunity but could protect the individual from severe
      disease, reduce the length of infection, and potentially reduce transmission in
      the community. Therefore, increasing the standard of care potentially offered by
      T cell vaccines should be considered in the context of pandemic preparedness and
      zoonotic infections, and in combination with improved antibody vaccine targeting
      methods. Current pandemic vaccine preparedness measures and ongoing clinical
      trials under-utilise T cell-inducing vaccines, reflecting the myriad questions
      that remain about how, when, where, and which T cells are needed to fight
      influenza virus infection. This review aims to bring together basic fundamentals
      of T cell biology with human clinical data, which need to be considered for the
      implementation of a universal vaccine against influenza that harnesses the power
      of T cells.

PMID- 29587438
TI  - Does Vitamin D Deficiency Affect the Immunogenic Responses to Influenza
      Vaccination? A Systematic Review and Meta-Analysis.
AB  - Influenza virus infection is a major global public health problem, and the
      efficacy of influenza vaccination is not satisfactory. Vitamin D is involved in
      many immune-mediated inflammatory processes. The impact of vitamin D levels on
      the immunogenic response to influenza vaccination is not clear. We performed a
      comprehensive literature search and systematic review of studies that
      investigated vitamin D and influenza vaccination. Data pertaining to study
      population, vaccine components, vitamin D levels, and immunogenic response were
      analyzed. Nine studies, with a combined study population of 2367 patients, were
      included in the systematic review. Four studies were included in the meta
      analysis to investigate the influence of vitamin D deficiency (VDD) on the
      seroprotection (SP) rates and seroconversion (SC) rates following influenza
      vaccination. We found no significant association between vitamin D level and the
      immunogenic response to influenza vaccination. However, strain-specific
      differences may exist. We observed lower SP rates of influenza A virus subtype
      H3N2 (A/H3N2) and B strain in VDD patients than patients with normal vitamin D
      levels (A/H3N2: 71.8% vs. 80.1%, odds ratio (OR): 0.63, 95% confidence interval
      (CI): 0.43-0.91, p = 0.01; B strain: 69.6% vs. 76.4%, OR: 0.68, 95% CI: 0.5-0.93,
      p = 0.01). However, the SP rates of A/H1N1 and SC rates of all three strains were
      not significantly different in VDD and control groups. In conclusion, no
      association was observed between VDD and immunogenic response to influenza
      vaccination.

PMID- 29587439
TI  - NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma.
AB  - The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor
      protein frequently inactivated in schwannoma, meningioma, and malignant
      mesothelioma (MM). The sequence of merlin is similar to that of
      ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma
      membrane, suggesting that merlin plays a role in transducing extracellular
      signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation
      defined by specific intramolecular interactions and regulates diverse cellular
      events such as transcription, translation, ubiquitination, and miRNA
      biosynthesis, many of which are mediated through Hippo and mTOR signaling, which
      are known to be closely involved in cancer development. MM is a very aggressive
      tumor associated with asbestos exposure, and genetic alterations in NF2 that
      abrogate merlin's functional activity are found in about 40% of MMs, indicating
      the importance of NF2 inactivation in MM development and progression. In this
      review, we summarize the current knowledge of molecular events triggered by
      NF2/merlin inactivation, which lead to the development of mesothelioma and other
      cancers, and discuss potential therapeutic targets in merlin-deficient
      mesotheliomas.

PMID- 29587440
TI  - 7-Acetylsinumaximol B Induces Apoptosis and Autophagy in Human Gastric Carcinoma
      Cells through Mitochondria Dysfunction and Activation of the
      PERK/eIF2alpha/ATF4/CHOP Signaling Pathway.
AB  - The 7-Acetylsinumaximol B (7-AB), a bioactive cembranoid, was originally
      discovered from aquaculture soft coral Sinularia sandensis. The current study
      investigated the anti-proliferative property of 7-AB towards the NCI-N87 human
      gastric cancer cell line. An MTT cell proliferative assay was applied to evaluate
      cell survival, and immunofluorescence staining and western blotting were employed
      to analyze the effects of 7-AB on autophagy and apoptosis. Our results showed
      that 7-AB exerted a concentration-dependent anti-proliferative effect on NCI-N87
      cells, and fluorescence staining indicated that the effect was due to the
      apoptosis induced by 7-AB. In addition, the 7-AB-induced anti-proliferation
      towards NCI-N87 cells was associated with the release of cytochrome c from
      mitochondria, activation of pro-apoptotic proteins (such as caspase-3/-9, Bax and
      Bad), and inhibition of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1). The 7
      AB treatment also triggered endoplasmic reticulum (ER) stress, leading to
      activation of the PERK/elF2alpha/ATF4/CHOP apoptotic pathway. Furthermore, 7-AB
      initiated autophagy in NCI-N87 cells and induced the expression of autophagy
      related proteins, including Atg3, Atg5, Atg7, Atg12, LC3-I, and LC3-II. Taken
      together, our findings suggested that 7-AB has the potential to be further
      developed as a useful anti-cancer or adjuvant agent for the treatment of human
      gastric cancer.

PMID- 29587441
TI  - Physical Activity Environment and Japanese Adults' Body Mass Index.
AB  - Evidence about the impacts of the physical activity environment on adults' weight
      in the context of Asian countries is scarce. Likewise, no study exists in Asia
      examining whether Walk Score(r)-a free online walkability tool-is related to
      obesity. This study aimed to examine associations between multiple physical
      activity environment measures and Walk Score(r) ratings with Japanese adults'
      body mass index (BMI). Data from 1073 adults in the Healthy Built Environment in
      Japan study were used. In 2011, participants reported their height and weight.
      Environmental attributes, including population density, intersection density,
      density of physical activity facilities, access to public transportation, and
      availability of sidewalks, were calculated using Geographic Information Systems.
      Walk Scores(r) ratings were obtained from the website. Multiple linear regression
      analysis was conducted to examine the association between each environmental
      attribute and BMI. Adjusting for covariates, all physical activity environmental
      attributes were negatively associated with BMI. Similarly, an increase of one
      standard deviation of Walk Score(r) was associated with a 0.29 (95% confidence
      interval (CI) of -0.49--0.09) decrease in BMI. An activity-friendly built
      environment was associated with lower adults' BMI in Japan. Investing in healthy
      community design may positively impact weight status in non-Western contexts.

PMID- 29587442
TI  - Junctional Adhesion Molecules (JAMs): The JAM-Integrin Connection.
AB  - Junctional adhesion molecules (JAMs) are cell surface adhesion receptors of the
      immunoglobulin superfamily. JAMs are involved in a variety of biological
      processes both in the adult organism but also during development. These include
      processes such as inflammation, angiogenesis, hemostasis, or epithelial barrier
      formation, but also developmental processes such as hematopoiesis, germ cell
      development, and development of the nervous system. Several of these functions of
      JAMs depend on a physical and functional interaction with integrins. The JAM -
      integrin interactions in trans regulate cell-cell adhesion, their interactions in
      cis regulate signaling processes originating at the cell surface. The JAM -
      integrin interaction can regulate the function of the JAM as well as the function
      of the integrin. Beyond the physical interaction with integrins, JAMs can
      regulate integrin function through intracellular signaling indicating an
      additional level of JAM - integrin cross-talk. In this review, we describe the
      various levels of the functional interplay between JAMs and integrins and the
      role of this interplay during different physiological processes.

PMID- 29587444
TI  - Microplastic Contamination of Wild and Captive Flathead Grey Mullet (Mugil
      cephalus).
AB  - A total of 60 flathead grey mullets were examined for microplastic ingestion.
      Thirty wild mullets were captured from the eastern coast of Hong Kong and 30
      captive mullets were obtained from fish farms. Microplastic ingestion was
      detected in 60% of the wild mullets, with an average of 4.3 plastic items per
      mullet, while only 16.7% of captive mullets were found to have ingested
      microplastics, with an average of 0.2 items per mullet. The results suggested
      that wild mullets have a higher risk of microplastic ingestion than their captive
      counterparts. The most common plastic items were fibres that were green in colour
      and small in size (<2 mm). Polypropylene was the most common polymer (42%),
      followed by polyethylene (25%). In addition, the abundance of microplastics was
      positively correlated with larger body size among the mullets.

PMID- 29587443
TI  - The Horizon of a Therapy for Rare Genetic Diseases: A "Druggable" Future for
      Fibrodysplasia Ossificans Progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition
      characterized by progressive extra-skeletal ossification leading to cumulative
      and severe disability. FOP has an extremely variable and episodic course and can
      be induced by trauma, infections, iatrogenic harms, immunization or can occur in
      an unpredictable way, without any recognizable trigger. The causative gene is
      ACVR1, encoding the Alk-2 type I receptor for bone morphogenetic proteins (BMPs).
      The signaling is initiated by BMP binding to a receptor complex consisting of
      type I and II molecules and can proceed into the cell through two main pathways,
      a canonical, SMAD-dependent signaling and a p38-mediated cascade. Most FOP
      patients carry the recurrent R206H substitution in the receptor Glycine-Serine
      rich (GS) domain, whereas a few other mutations are responsible for a limited
      number of cases. Mutations cause a dysregulation of the downstream BMP-dependent
      pathway and make mutated ACVR1 responsive to a non-canonical ligand, Activin A.
      There is no etiologic treatment for FOP. However, many efforts are currently
      ongoing to find specific therapies targeting the receptor activity and the
      downstream aberrant pathway at different levels or targeting cellular components
      and/or processes that are important in modifying the local environment leading to
      bone neo-formation.

PMID- 29587445
TI  - Parental Nitrogen Transfer and Apparent Absence of N2 Fixation during Colony
      Foundation in Coptotermes formosanus Shiraki.
AB  - Colony foundation and early growth is a critical period in the life-cycle of a
      termite colony, as the initial family unit is resource limited. One such resource
      is nitrogen, which is essential for initial colony growth. This study examined
      the whole-colony nitrogen inventory during foundation and early growth of
      Coptotermes formosanus Shiraki colonies. It was hypothesized that termite
      colonies would go through an initial period of parental investment, representing
      a transfer of nitrogen to the first brood, and that once a functional worker
      caste was present, further provisioning in the form of intrinsic N2 fixation
      would occur. Our results showed that, when in nitrogen-poor rearing conditions,
      the king and queen initially transferred half of their nitrogen reserves to their
      first brood. However, the total nitrogen content in colonies did not increase
      over a 12 month period, despite the presence of functional workers. Furthermore,
      colonies did not increase their biomass beyond the initial parental investment.
      Together, these results imply that nitrogen acquisition in incipient C.
      formosanus colonies relies on environmental or dietary sources, rather than the
      putative fixation through symbiotic diazotrophs.

PMID- 29587446
TI  - Legionella spp. Risk Assessment in Recreational and Garden Areas of Hotels.
AB  - Several Travel-associated Legionnaires' disease (TALD) cases occur annually in
      Europe. Except from the most obvious sites (cooling towers and hot water
      systems), infections can also be associated with recreational, water feature, and
      garden areas of hotels. This argument is of great interest to better comprehend
      the colonization and to calculate the risk to human health of these sites. From
      July 2000-November 2017, the public health authorities of the Island of Crete
      (Greece) inspected 119 hotels associated with TALD, as reported through the
      European Legionnaires' Disease Surveillance Network. Five hundred and eighteen
      samples were collected from decorative fountain ponds, showers near pools and
      spas, swimming pools, spa pools, garden sprinklers, drip irrigation systems
      (reclaimed water) and soil. Of those, 67 (12.93%), originating from 43 (35.83%)
      hotels, tested positive for Legionella (Legionella pneumophila serogroups 1, 2,
      3, 6, 7, 8, 13, 14, 15 and non-pneumophila species (L. anisa, L. erythra, L.
      taurinensis, L. birminghamensis, L. rubrilucens). A Relative Risk (R.R.) > 1 (p <
      0.0001) was calculated for chlorine concentrations of less than 0.2 mg/L (R.R.:
      54.78), star classification (<4) (R.R.: 4.75) and absence of Water Safety Plan
      implementation (R.R.: 3.96). High risk (>=104 CFU/L) was estimated for pool
      showers (16.42%), garden sprinklers (7.46%) and pool water (5.97%).

PMID- 29587447
TI  - Duration of Breastfeeding, but Not Timing of Solid Food, Reduces the Risk of
      Overweight and Obesity in Children Aged 24 to 36 Months: Findings from an
      Australian Cohort Study.
AB  - This study aimed to determine whether breastfeeding duration and the timing of
      solid food were independently associated with being overweight or obese in early
      childhood. Subjects were 953 children participating in the Study of Mothers and
      Infants Life Events Affecting Oral Health (SMILE) birth cohort study, based in
      Adelaide, Australia. Socio-demographic information and data on breastfeeding
      duration and age of introduction of solid food were collected at birth, 3, 4, 6,
      12, and 24 months via mailed or online questionnaires completed by mothers. The
      weight and height of children were measured at a dental examination when children
      were aged between 24 and 36 months. Body mass index was calculated, and children
      were categorised into weight groups according to the World Health Organization
      growth standards. Multivariable logistic regression analysis was conducted,
      adjusting for maternal age at birth, education, socio-economic status, pre
      pregnancy weight, smoking in pregnancy, method of delivery, and child's
      birthweight. Risk of overweight/obesity was independently associated with
      maternal pre-pregnancy BMI, smoking in pregnancy, and birthweight. Children that
      were breastfed for 12 months or more had a significantly lower risk of being
      overweight/obese than those breastfed for less than 17 weeks (AOR 0.49; 95%CI
      0.27, 0.90; p for trend =0.009). Age of introduction of solid food, however, was
      not associated with the risk of being overweight/obese at 24 to 36 months. This
      study provides further evidence of an inverse relationship between breastfeeding
      and risk of overweight/obesity, however, no association with the timing of solid
      food was detected.

PMID- 29587448
TI  - Development of Implantable Wireless Sensor Nodes for Animal Husbandry and MedTech
      Innovation.
AB  - In this paper, we report the development, evaluation, and application of ultra
      small low-power wireless sensor nodes for advancing animal husbandry, as well as
      for innovation of medical technologies. A radio frequency identification (RFID)
      chip with hybrid interface and neglectable power consumption was introduced to
      enable switching of ON/OFF and measurement mode after implantation. A wireless
      power transmission system with a maximum efficiency of 70% and an access distance
      of up to 5 cm was developed to allow the sensor node to survive for a duration of
      several weeks from a few minutes' remote charge. The results of field tests using
      laboratory mice and a cow indicated the high accuracy of the collected biological
      data and bio-compatibility of the package. As a result of extensive application
      of the above technologies, a fully solid wireless pH sensor and a surgical
      navigation system using artificial magnetic field and a 3D MEMS magnetic sensor
      are introduced in this paper, and the preliminary experimental results are
      presented and discussed.

PMID- 29587449
TI  - Embedded Distributed Optical Fiber Sensors in Reinforced Concrete Structures-A
      Case Study.
AB  - When using distributed optical fiber sensors (DOFS) on reinforced concrete
      structures, a compromise must be achieved between the protection requirements and
      robustness of the sensor deployment and the accuracy of the measurements both in
      the uncracked and cracked stages and under loading, unloading and reloading
      processes. With this in mind the authors have carried out an experiment where
      polyimide-coated DOFS were installed on two concrete beams, both embedded in the
      rebar elements and also bonded to the concrete surface. The specimens were
      subjected to a three-point load test where after cracking, they are unloaded and
      reloaded again to assess the capability of the sensor when applied to a real
      loading scenarios in concrete structures. Rayleigh Optical Frequency Domain
      Reflectometry (OFDR) was used as the most suitable technique for crack detection
      in reinforced concrete elements. To verify the reliability and accuracy of the
      DOFS measurements, additional strain gauges were also installed at three
      locations along the rebar. The results show the feasibility of using a thin
      coated polyimide DOFS directly bonded on the reinforcing bar without the need of
      indention or mechanization. A proposal for a Spectral Shift Quality (SSQ)
      threshold is also obtained and proposed for future works when using polyimide
      coated DOFS bonded to rebars with cyanoacrylate adhesive.

PMID- 29587450
TI  - A Resource Service Model in the Industrial IoT System Based on Transparent
      Computing.
AB  - The Internet of Things (IoT) has received a lot of attention, especially in
      industrial scenarios. One of the typical applications is the intelligent mine,
      which actually constructs the Six-Hedge underground systems with IoT platforms.
      Based on a case study of the Six Systems in the underground metal mine, this
      paper summarizes the main challenges of industrial IoT from the aspects of
      heterogeneity in devices and resources, security, reliability, deployment and
      maintenance costs. Then, a novel resource service model for the industrial IoT
      applications based on Transparent Computing (TC) is presented, which supports
      centralized management of all resources including operating system (OS), programs
      and data on the server-side for the IoT devices, thus offering an effective,
      reliable, secure and cross-OS IoT service and reducing the costs of IoT system
      deployment and maintenance. The model has five layers: sensing layer, aggregation
      layer, network layer, service and storage layer and interface and management
      layer. We also present a detailed analysis on the system architecture and key
      technologies of the model. Finally, the efficiency of the model is shown by an
      experiment prototype system.

PMID- 29587451
TI  - Integrated Optoelectronic Position Sensor for Scanning Micromirrors.
AB  - Scanning micromirrors have been used in a wide range of areas, but many of them
      do not have position sensing built in, which significantly limits their
      application space. This paper reports an integrated optoelectronic position
      sensor (iOE-PS) that can measure the linear displacement and tilting angle of
      electrothermal MEMS (Micro-electromechanical Systems) scanning mirrors. The iOE
      PS integrates a laser diode and its driving circuits, a quadrant photo-detector
      (QPD) and its readout circuits, and a band-gap reference all on a single chip,
      and it has been fabricated in a standard 0.5 MUm CMOS (Complementary Metal Oxide
      Semiconductor) process. The footprint of the iOE-PS chip is 5 mm * 5 mm. Each
      quadrant of the QPD has a photosensitive area of 500 um * 500 um and the spacing
      between adjacent quadrants is 500 MUm. The iOE-PS chip is simply packaged
      underneath of an electrothermally-actuated MEMS mirror. Experimental results show
      that the iOE-PS has a linear response when the MEMS mirror plate moves vertically
      between 2.0 mm and 3.0 mm over the iOE-PS chip or scans from -5 to +5 degrees .
      Such MEMS scanning mirrors integrated with the iOE-PS can greatly reduce the
      complexity and cost of the MEMS mirrors-enabled modules and systems.

PMID- 29587452
TI  - Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of
      Anticancer Aryltetralin Lignans.
AB  - Linum flavum hairy root lines were established from hypocotyl pieces using
      Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were
      effective for transformation but induction of hairy root phenotype was more
      stable with strain ATCC 15834. Whereas similar accumulation patterns were
      observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin,
      podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations
      were noted between root lines. The influence of culture medium and various
      treatments (hormone, elicitation and precursor feeding) were evaluated. The
      highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl
      jasmonate, and feeding using ferulic acid increased the accumulation of
      aryltetralin lignans. These results point to the use of hairy root culture lines
      of Linum flavum as potential sources for these valuable metabolites as an
      alternative, or as a complement to Podophyllum collected from wild stands.

PMID- 29587454
TI  - Special Issue: Mucosal Fungal Infections.
AB  - The past four decades have seen a staggering escalation in the number of invasive
      fungal infections worldwide.[...].

PMID- 29587453
TI  - Low Serum Levels of (Dihydro-)Ceramides Reflect Liver Graft Dysfunction in a Real
      World Cohort of Patients Post Liver Transplantation.
AB  - Patients after orthopic liver transplantation (OLT) are at risk of developing
      graft dysfunction. Sphingolipids (SL's) have been identified to play a pivotal
      role in the regulation of hepatocellular apoptosis, inflammation and immunity. We
      aimed to investigate the serum SL profile in a prospective real-world cohort of
      post-OLT patients. From October 2015 until July 2016, 149 well-characterized post
      OLT patients were analyzed. SL's were assessed in serum probes via Liquid
      Chromatography/Tandem Mass Spectrometry. Twenty-nine (20%) patients had a biopsy
      proven graft rejection with decreased C20-ceramide (Cer) (p = 0.042), C18
      dihydroceramide (DHC) (p = 0.022) and C24DHC (p = 0.060) levels. Furthermore,
      C18DHC (p = 0.044) and C24DHC (p = 0.011) were significantly down-regulated in
      patients with ischemic type biliary lesions (ITBL; n = 15; 10%). One-hundred and
      thirty-three patients (89%) have so far received tacrolimus as the main
      immunosuppressive agent with observed elevations of C14Cer (p = 0.052), C18Cer (p
      = 0.049) and C18:1Cer (p = 0.024). Hepatocellular carcinoma (HCC) pre-OLT was
      associated with increases in C24:1Cer (p = 0.024) and C24:1DHC (p = 0.024). In
      this large prospective cross-sectional study of patients, post-OLT serum levels
      of (very-)long chain (dihydro-)ceramides associate with graft rejection, ITBL,
      tacrolimus intake and HCC pre-OLT. Hence, serum SL's may be indicative of graft
      complications. Further research is necessary to identify their diverse
      mechanistic role in regulating immunity and inflammation in patients post-OLT.

PMID- 29587455
TI  - Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the
      ESBRA 2017 Congress.
AB  - The symposium, "Role of Nutrition in Alcoholic Liver Disease", was held at the
      European Society for Biomedical Research on Alcoholism Congress on 9 October 2017
      in Crete, Greece. The goal of the symposium was to highlight recent advances and
      developments in the field of alcohol and nutrition. The symposium was focused on
      experimental and clinical aspects in relation to the role of different types of
      dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease
      (ALD). The following is a summary of key research presented at this session. The
      speakers discussed the role of dietary fats and carbohydrates in the development
      and progression of alcohol-induced multi-organ pathology in animal models of ALD,
      analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in
      the treatment of ALD, and addressed clinical relevance of malnutrition and
      nutrition support in ALD. This summary of the symposium will benefit junior and
      senior faculty currently investigating alcohol-induced organ pathology as well as
      undergraduate, graduate, and post-graduate students and fellows.

PMID- 29587456
TI  - Review of Stratum Corneum Impedance Measurement in Non-Invasive Penetration
      Application.
AB  - Due to advances in telemedicine, mobile medical care, wearable health monitoring,
      and electronic skin, great efforts have been directed to non-invasive monitoring
      and treatment of disease. These processes generally involve disease detection
      from interstitial fluid (ISF) instead of blood, and transdermal drug delivery.
      However, the quantitative extraction of ISF and the level of drug absorption are
      greatly affected by the individual's skin permeability, which is closely related
      to the properties of the stratum corneum (SC). Therefore, measurement of SC
      impedance has been proposed as an appropriate way for assessing individual skin
      differences. In order to figure out the current status and research direction of
      human SC impedance detection, investigations regarding skin impedance measurement
      have been reviewed in this paper. Future directions are concluded after a review
      of impedance models, electrodes, measurement methods and systems, and their
      applications in treatment. It is believed that a well-matched skin impedance
      model and measurement method will be established for clinical and point-of care
      applications in the near future.

PMID- 29587457
TI  - An Experimental Study of a Micro-Projection Enabled Optical Terminal for Short
      Range Bidirectional Multi-Wavelength Visible Light Communications.
AB  - A micro-projection enabled short-range communication (SRC) approach using red-,
      green- and blue-based light-emitting diodes (RGB-LEDs) has experimentally
      demonstrated recently that micro-projection and high-speed data transmission can
      be performed simultaneously. In this research, a reconfigurable design of a
      polarization modulated image system based on the use of a Liquid Crystal on
      Silicon based Spatial Light Modulator (LCoS-based SLM) serving as a portable
      optical terminal capable of micro-projection and bidirectional multi-wavelength
      communications is proposed and experimentally demonstrated. For the proof of
      concept, the system performance was evaluated through a bidirectional
      communication link at a transmission distance over 0.65 m. In order to make the
      proposed communication system architecture compatible with the data modulation
      format of future possible wireless communication system, baseband modulation
      scheme, i.e., Non-Return-to-Zero On-Off-Keying (NRZ_OOK), M-ary Phase Shift
      Keying (M-PSK) and M-ary Quadrature Amplitude Modulation (M-QAM) were used to
      investigate the system transmission performance. The experimental results shown
      that an acceptable BER (satisfying the limitation of Forward Error Correction,
      FEC standard) and crosstalk can all be achieved in the bidirectional multi
      wavelength communication scenario.

PMID- 29587459
TI  - Seed Hydropriming and Smoke Water Significantly Improve Low-Temperature
      Germination of Lupinus angustifolius L.
AB  - Seed imbibition under cold temperature is dangerous when dry seeds have
      relatively low water content. The aim of this study was to investigate
      germination of 20 lines/cultivars of narrow-leaf lupine at 7  degrees C (cold)
      and 13  degrees C (control) under the influence of smoke water and following seed
      hydropriming for 3 h at 20  degrees C. The efficacy of individual treatments was
      examined with regard to seed protection during low-temperature germination. Based
      on seed germination, vigour at cold was evaluated four days after sowing by means
      of hypocotyl length, the studied lines/cultivars were divided into three groups
      with low, high and very high germination rates. Germination vigour correlated
      with cell membrane permeability, dehydrogenase activity and abscisic acid (ABA)
      content and was analysed in the seeds one day after sowing. Gibberellin content
      did not correlate with germination vigour. The seeds of weakly germinating
      lines/cultivars had the highest cell permeability and ABA content as well as the
      lowest amylolytic activity at both studied temperatures. Additionally, the vigour
      of weakly germinating seeds at 7  degrees C correlated with dehydrogenase
      activity. Three-hour hydropriming was the most effective for seed germination
      under cold due to reduced cell membrane permeability and ABA level. Stimulating
      effects of smoke water on germination under cold could be explained by enhanced
      dehydrogenase activity.

PMID- 29587460
TI  - Analytical Method to Estimate the Complex Permittivity of Oil Samples.
AB  - In this paper, an analytical method to estimate the complex dielectric constant
      of liquids is presented. The method is based on the measurement of the
      transmission coefficient in an embedded microstrip line loaded with a
      complementary split ring resonator (CSRR), which is etched in the ground plane.
      From this response, the dielectric constant and loss tangent of the liquid under
      test (LUT) can be extracted, provided that the CSRR is surrounded by such LUT,
      and the liquid level extends beyond the region where the electromagnetic fields
      generated by the CSRR are present. For that purpose, a liquid container acting as
      a pool is added to the structure. The main advantage of this method, which is
      validated from the measurement of the complex dielectric constant of olive and
      castor oil, is that reference samples for calibration are not required.

PMID- 29587458
TI  - Towards an Integrative Understanding of tRNA Aminoacylation-Diet-Host-Gut
      Microbiome Interactions in Neurodegeneration.
AB  - Transgenic mice used for Alzheimer's disease (AD) preclinical experiments do not
      recapitulate the human disease. In our models, the dietary tryptophan metabolite
      tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase
      (TrpRS) deficiency with consequent neurodegeneration in cells and mice. Dietary
      supplements, antibiotics and certain drugs increase tryptamine content in vivo.
      TrpRS catalyzes tryptophan attachment to tRNAtrp at initial step of protein
      biosynthesis. Tryptamine that easily crosses the blood-brain barrier induces
      vasculopathies, neurodegeneration and cell death via TrpRS competitive
      inhibition. TrpRS inhibitor tryptophanol produced by gut microbiome also induces
      neurodegeneration. TrpRS inhibition by tryptamine and its metabolites preventing
      tryptophan incorporation into proteins lead to protein biosynthesis impairment.
      Tryptophan, a least amino acid in food and proteins that cannot be synthesized by
      humans competes with frequent amino acids for the transport from blood to brain.
      Tryptophan is a vulnerable amino acid, which can be easily lost to protein
      biosynthesis. Some proteins marking neurodegenerative pathology, such as tau lack
      tryptophan. TrpRS exists in cytoplasmic (WARS) and mitochondrial (WARS2) forms.
      Pathogenic gene variants of both forms cause TrpRS deficiency with consequent
      intellectual and motor disabilities in humans. The diminished tryptophan
      dependent protein biosynthesis in AD patients is a proof of our model-based
      disease concept.

PMID- 29587461
TI  - The Impact of T-2 Toxin on Vasoactive Intestinal Polypeptide-Like Immunoreactive
      (VIP-LI) Nerve Structures in the Wall of the Porcine Stomach and Duodenum.
AB  - T-2 toxin is a secondary metabolite of some Fusarium species. It is well-known
      that this substance can harmfully impact living organisms. Among others, thanks
      to the ability of crossing the blood-brain barrier, T-2 toxin can affect the
      central nervous system. Mycotoxins mostly get into the organism through the
      digestive tract; therefore, first of all they have to break the intestinal
      barrier, wherein the important component is the enteric nervous system (ENS).
      However, knowledge about the impact of T-2 toxin on the ENS is rather scant. As a
      result of the influence of various physiological and pathological agents, ENS can
      undergo adaptive and reparative processes which manifest as changes in the
      immunoreactivity of perikaryons for neuronal active substances. So, the aim of
      the present investigation was to study how low doses of T-2 toxin affect
      vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nervous structures
      in the ENS of the porcine stomach and duodenum. Obtained results have shown that
      T-2 toxin causes an percentage increase of VIP-LI nerve cells and nerve fibers in
      every enteric plexus in both fragments of gastrointestinal tract studied. This
      shows that even low doses of T-2 toxin can have an influence on living organisms.

PMID- 29587462
TI  - Intraconversion of Polar Ginsenosides, Their Transformation into Less-Polar
      Ginsenosides, and Ginsenoside Acetylation in Ginseng Flowers upon Baking and
      Steaming.
AB  - Heating is a traditional method used in ginseng root processing, however, there
      aren't reports on differences resulting from baking and steaming. Moreover,
      ginseng flowers, with 5.06 times more total saponins than ginseng root, are not
      fully taken advantage of for their ginsenosides. Transformation mechanisms of
      ginsenosides in ginseng flowers upon baking and steaming were thus explored. HPLC
      using authentic standards of 20 ginsenosides and UPLC-QTOF-MS/MS were used to
      quantify and identify ginsenosides, respectively, in ginseng flowers baked or
      steamed at different temperatures and durations. Results show that baking and
      steaming caused a 3.2-fold increase in ginsenoside species existed in unheated
      ginseng flowers (20/64 ginsenosides) and transformation of a certain amount of
      polar ginsenosides into numerous less polar ginsenosides. Among the 20
      ginsenosides with standards, polar ginsenosides were abundant in ginseng flowers
      baked or steamed at lower temperatures, whereas less polar ginsenosides occurred
      and were enriched at higher temperatures. Furthermore, the two types of heating
      treatments could generate mostly similar ginsenosides, but steaming was much
      efficient than baking in transforming polar- into less polar ginsenosides, with
      steaming at 120  degrees C being comparably equivalent to baking at 150  degrees
      C. Moreover, both the two heating methods triggered ginsenoside acetylation and
      thus caused formation of 16 acetylginsenosides. Finally, a new transformation
      mechanism concerning acetyl-ginsenosides formation was proposed.

PMID- 29587463
TI  - Study of Adsorption Mechanism of Congo Red on Graphene Oxide/PAMAM Nanocomposite.
AB  - Graphene oxide/poly(amidoamine) (GO/PAMAM) nanocomposite adsorbed high quantities
      of congo red (CR) anionic dye in 0.1 M NaCl solution, with the maximum adsorption
      capacity of 198 mg.g-1. The kinetics and thermodynamics of adsorption were
      investigated to elucidate the effects of pH, temperature, shaking rate, ionic
      strength, and contact time. Kinetic data were analyzed by the KASRA model and the
      KASRA, ISO, and pore-diffusion equations. Adsorption adsorption isotherms were
      studied by the ARIAN model and the Henry, Langmuir, and Temkin equations. It was
      shown that adsorption sites of GO/PAMAM at experimental conditions were phenolic
      hydroxyl groups of GO sheets and terminal amine groups of PAMAM dendrimer.
      Analysis of kinetic data indicated that amine sites were located on the surface,
      and that hydroxyl sites were placed in the pores of adsorbent. CR molecules
      interacted with the adsorption sites via hydrogen bonds. The molecules were
      adsorbed firstly on the amine sites, and then on the internal hydroxyl sites.
      Adsorption kinetic parameters indicated that the interaction of CR to the -NH3+
      sites was the rate-controlling step of adsorption of CR on this site and
      adsorption activation energies calculated for different parts of this step. On
      the other hand, kinetic parameters showed that the intraparticle diffusion was
      the rate-controlling step during the interaction of CR molecules to -OH sites and
      activation energy of this step was not calculable. Finally, the used GO/PAMAM was
      completely regenerated by using ethylenediamine.

PMID- 29587464
TI  - Design and Processing of a Novel Chaos-Based Stepped Frequency Synthesized
      Wideband Radar Signal.
AB  - The linear stepped frequency and linear frequency shift keying (FSK) signal has
      been widely used in radar systems. However, such linear modulation signals suffer
      from the range-Doppler coupling that degrades radar multi-target resolution.
      Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily
      predicted by the interception receiver in the electronic countermeasures (ECM)
      environments, which limits radar anti-jamming performance. In addition, the
      single FSK modulation reduces the radar low probability of intercept (LPI)
      performance, for it cannot achieve a large time-bandwidth product. To solve such
      problems, we propose a novel chaos-based stepped frequency (CSF) synthesized
      wideband signal in this paper. The signal introduces chaotic frequency hopping
      between the coherent stepped frequency pulses, and adopts a chaotic frequency
      shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a
      subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the
      signal has been proposed. According to our theoretical analyses and the
      simulations, the proposed signal and processing method achieve better multi
      target resolution and LPI performance. Furthermore, flexible modulation is able
      to increase the robustness against identification of the interception receiver
      and improve the anti-jamming performance of the radar.

PMID- 29587465
TI  - MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by
      Modulating the Gut Microbiota.
AB  - The gut microbiota and microRNAs play important roles in the defense against
      infection. However, the role of miR-146a in L. monocytogenes infection and gut
      microbiota remains unclear. We tried to determine whether miR-146a controlled L.
      monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a
      deficient mice or macrophages were used to characterize the impact of miR-146a on
      animal survival, cell death, bacterial clearance, and gut microbiota following L.
      monocytogenes challenge. We found that L. monocytogenes infection induced miR
      146a expression both in vitro and in vivo. When compared to wild-type mice, miR
      146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a
      deficiency in macrophages resulted in reduced invasion and intracellular survival
      of L. monocytogenes. High-throughput sequencing of 16S rRNA revealed that the gut
      microbiota composition differed between miR-146a-deficient and wild-type mice.
      Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the
      Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and
      significantly increased short-chain fatty acid producing bacteria, including the
      genera Alistipes, Blautia, Coprococcus_1, and Ruminococcus_1. Wild-type mice co
      housed with miR-146a-deficient mice had increased resistance to L. monocytogenes,
      indicating that miR-146a deficiency guides the gut microbiota to alleviate
      infection. Together, these results suggest that miR-146a deficiency protects
      against L. monocytogenes infection by regulating the gut microbiota.

PMID- 29587467
TI  - Sandwich-Type Nitrogen and Sulfur Codoped Graphene-Backboned Porous Carbon Coated
      Separator for High Performance Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries have been identified as the greatest potential
      next- generation energy-storage systems because of the large theoretical energy
      density of 2600 Wh kg-1. However, its practical application on a massive scale is
      impeded by severe capacity loss resulted from the notorious polysulfides shuttle.
      Here, we first present a novel technique to synthesize sandwich-type nitrogen and
      sulfur codoped graphene-backboned porous carbon (NSGPC) to modify the commercial
      polypropylene separator in Li-S batteries. The as-synthesized NSGPC exhibits a
      unique micro/mesoporous carbon framework, large specific surface area (2439.0 m2
      g-1), high pore volume (1.78 cm3 g-1), good conductivity, and in situ nitrogen
      (1.86 at %) and sulfur (5.26 at %) co-doping. Benefiting from the particular
      physical properties and chemical components of NSGPC, the resultant NSGPC-coated
      separator not only can facilitate rapid Li+ ions and electrons transfer, but also
      can restrict the dissolution of polysulfides to alleviate the shuttle effect by
      combining the physical absorption and strong chemical adsorption. As a result, Li
      S batteries with NSGPC-coated separator exhibit high initial reversible capacity
      (1208.6 mAh g-1 at 0.2 C), excellent rate capability (596.6 mAh g-1 at 5 C), and
      superior cycling stability (over 500 cycles at 2 C with 0.074% capacity decay
      each cycle). Propelling our easy-designed pure sulfur cathode to a extremely
      increased mass loading of 3.4 mg cm-2 (70 wt. % sulfur), the Li-S batteries with
      this functional composite separator exhibit a superior high initial capacity of
      1171.7 mAh g-1, which is quite beneficial to commercialized applications.

PMID- 29587469
TI  - Coupling Vibration Analysis of Trapped-Energy Rectangular Quartz Resonators by
      Variational Formulation of Mindlin's Theory.
AB  - Mindlin's two-dimensional theory has been derived and applied to research on
      quartz resonators for a long time. However, most works have focused on vibrations
      varying only in two directions, including thickness direction, while the effect
      of other directions like the length or width direction is normally neglected.
      Besides, researchers often model quartz resonators as fully electroded plates
      because of the resulting simplicity. Since a real device is finite in all
      directions and is only centrally electroded, results obtained in such works
      cannot offer quantitative information on vibrations with enough accuracy. In this
      paper, a theoretical analysis of a rectangular trapped-energy resonator of AT-cut
      quartz is studied using the Ritz method, associated with the variational
      formulation of Mindlin's first-order equations. Frequency spectra and mode shapes
      of a real-scaled trapped-energy resonator, which is finite in all directions, are
      obtained with the consideration of mode couplings among thickness-shear mode,
      thickness-twist mode, and flexural mode. Results show the existence of an energy
      trapping and coupling phenomenon and are helpful for thorough and accurate
      understanding of quartz resonator vibrations. Detailed discussions on the effects
      of structural parameters on mode couplings and energy trapping are provided, and
      the results can helpfully guide the selection of aspect ratio, length/thickness
      ratio, and electrode inertia in device design.

PMID- 29587466
TI  - Chromosomal Instability in Hodgkin Lymphoma: An In-Depth Review and Perspectives.
AB  - The study of Hodgkin lymphoma (HL), with its unique microenvironment and long
      term follow-up, has provided exceptional insights into several areas of tumor
      biology. Findings in HL have not only improved our understanding of human
      carcinogenesis, but have also pioneered its translation into the clinics. HL is a
      successful paradigm of modern treatment strategies. Nonetheless, approximately 15
      20% of patients with advanced stage HL still die following relapse or progressive
      disease and a similar proportion of patients are over-treated, leading to
      treatment-related late sequelae, including solid tumors and organ dysfunction.
      The malignant cells in HL are characterized by a highly altered genomic landscape
      with a wide spectrum of genomic alterations, including somatic mutations, copy
      number alterations, complex chromosomal rearrangements, and aneuploidy. Here, we
      review the chromosomal instability mechanisms in HL, starting with the cellular
      origin of neoplastic cells and the mechanisms supporting HL pathogenesis,
      focusing particularly on the role of the microenvironment, including the
      influence of viruses and macrophages on the induction of chromosomal instability
      in HL. We discuss the emerging possibilities to exploit these aberrations as
      prognostic biomarkers and guides for personalized patient management.

PMID- 29587468
TI  - Application of the P300 Event-Related Potential in the Diagnosis of Epilepsy
      Disorder: A Review.
AB  - Epilepsy is one of the most serious chronical neurological disorders, affecting
      more than 50 million people worldwide. It can be defined as a spectrum disorder,
      and patients with epilepsy possess abnormalities in cognitive functions. A number
      of factors can cause cognitive dysfunctions in epileptic syndromes, including
      etiology, the age of onset, type of seizure and severity, duration, and
      antiepileptic drugs. Event-related potentials (ERPs) are very useful clinical and
      research instruments to evaluate cognitive function in patients with
      neuropsychiatry disorders. Event-related potentials directly reflect cortical
      neuronal activity and provide a particular level of temporal resolution. Among
      various ERP components, the P300 is the most important component for assessing
      cognitive processes such as attention, working memory, and concentration.
      Numerous studies have reported the abnormalities in amplitude or latency of P300
      component of ERP in epileptic patients, and these abnormalities are indicative of
      cognitive dysfunction. Therefore, the purpose of this review is to consolidate
      the existing literature in connection with the use of P300 in epileptic patients.

PMID- 29587470
TI  - Global Correlates of Cardiovascular Risk: A Comparison of 158 Countries.
AB  - The aim of this study was a large-scale ecological analysis of nutritional and
      other environmental factors potentially associated with the incidence of
      cardiovascular diseases (CVDs) in the global context. Indicators of CVDs from 158
      countries were compared with the statistics of mean intake (supply) of 60 food
      items between 1993 and 2011, obesity rates, health expenditure and life
      expectancy. This comparison shows that the relationship between CVD indicators
      (raised blood pressure, CVD mortality, raised blood glucose) and independent
      variables in the global context is influenced by various factors, such as short
      life expectancy, religiously conditioned dietary customs, the imprecision of some
      statistics and undernutrition. However, regardless of the statistical method
      used, the results always show very similar trends and identify high carbohydrate
      consumption (mainly in the form of cereals and wheat, in particular) as the
      dietary factor most consistently associated with the risk of CVDs. These findings
      are in line with the changing view of the causes of CVDs. Because the statistics
      of raised blood glucose only include people using medications and do not reflect
      true prevalence that is independent of healthcare, more objective data on the
      prevalence of CVDs are needed to confirm these observed trends.

PMID- 29587471
TI  - Effects of Two Doses of Curry Prepared with Mixed Spices on Postprandial Ghrelin
      and Subjective Appetite Responses-A Randomized Controlled Crossover Trial.
AB  - Spices are known to provide orosensory stimulation that can potentially influence
      palatability, appetite, and energy balance. Previous studies with individual
      spices have shown divergent effects on appetite and energy intake measures. In a
      real-life context, however, several spices are consumed in combinations, as in
      various forms of curries. Therefore, we investigated changes in postprandial
      appetite and plasma ghrelin in response to the intake of two doses of curry
      prepared with mixed spices. The study was undertaken in healthy Chinese men,
      between 21 and 40 years of age and body mass index <=27.5 kg/m2. Appetite was
      measured using visual analogue scales (VAS) and plasma ghrelin was measured using
      multiplex assay. Compared with the control meal (Dose 0 Control (D0C), 0 g mixed
      spices), we found significantly greater suppression in 'hunger' (both p < 0.05,
      after Bonferroni adjustments) as well in 'desire to eat' (both p < 0.01) during
      the Dose 1 Curry (D1C, 6 g mixed spices) and Dose 2 Curry (D2C, 12 g mixed
      spices) intake. There were no differences, however, in plasma ghrelin or in other
      appetite measures such as in 'fullness' or in 'prospective eating' scores.
      Overall, the results of our study indicate greater inter-meal satiety due to
      mixed spices consumption, independent of any changes in plasma ghrelin response.

PMID- 29587472
TI  - 2D Analytical Model for the Directivity Prediction of Ultrasonic Contact Type
      Transducers in the Generation of Guided Waves.
AB  - In this paper, a novel 2D analytical model based on the Huygens's principle of
      wave propagation is proposed in order to predict the directivity patterns of
      contact type ultrasonic transducers in the generation of guided waves (GWs). The
      developed model is able to estimate the directivity patterns at any distance, at
      any excitation frequency and for any configuration and shape of the transducers
      with prior information of phase dispersive characteristics of the guided wave
      modes and the behavior of transducer. This, in turn, facilitates to choose the
      appropriate transducer or arrays of transducers, suitable guided wave modes and
      excitation frequency for the nondestructive testing (NDT) and structural health
      monitoring (SHM) applications. The model is demonstrated for P1-type macro-fiber
      composite (MFC) transducer glued on a 2 mm thick aluminum (Al) alloy plate. The
      directivity patterns of MFC transducer in the generation of fundamental guided
      Lamb modes (the S0 and A0) and shear horizontal mode (the SH0) are successfully
      obtained at 80 kHz, 5-period excitation signal. The results are verified using 3D
      finite element (FE) modelling and experimental investigation. The results
      obtained using the proposed model shows the good agreement with those obtained
      using numerical simulations and experimental analysis. The calculation time using
      the analytical model was significantly shorter as compared to the time spent in
      experimental analysis and FE numerical modelling.

PMID- 29587473
TI  - Zn(OAc)2-Catalyzing Ring-Opening Polymerization of N-Carboxyanhydrides for the
      Synthesis of Well-Defined Polypeptides.
AB  - Despite notable progress, the fabrication of well-defined polypeptides via
      controlled ring-opening polymerization (ROP) of alpha-amino acid N
      carboxyanhydrides (NCAs) using convenient catalysts under mild conditions in a
      relatively short polymerization time is still challenging. Herein, an easily
      obtained catalyst system composed of zinc acetate and aniline was explored to
      mediate the fast ROP of gamma-benzyl-l-glutamate-N-carboxyanhydride (BLG-NCA)
      monomer, to produce poly(gamma-benzyl-l-glutamates) (PBLGs) with controllable
      molecular weights and narrow dispersity. Considering the excellent cooperative
      action of zinc acetate and a broad scope of aniline derivatives with different
      functional groups to control ROP of BLG-NCA, this method may offer a useful
      platform enabling the rapid generation of end-functionalized PBLG and block
      copolymers for numerous biomedical applications.

PMID- 29587474
TI  - Evaluation of the Possible Neurotoxic Effect of the Bone Cement on the Facial
      Nerve: An Experimental Study.
AB  - OBJECTIVES: To investigate neurotoxic effect of bone cement (BC) on facial nerve
      by using electrophysiological and histopathological methods. METHODS: This study
      included 20 male albino Wistar rats, divided into four equal groups. Group A was
      designed as the control group, while group B was sham group. In the group C, BC
      solution was dropped onto the facial nerve trunks of rats and washed with
      physiological saline after 5 seconds. In the group D, BC solution was dropped
      onto the facial nerve trunks of rats and after allowing 5 minutes to dry, wounds
      were closed. Pre- and postoperative (on 4th week) evoked electromyography (EMG)
      measurements were done. For histopathological assessments, the rats were
      euthanized and tissue samples of facial nerve and surrounding areas were
      collected. RESULTS: According to the wave amplitude levels of evoked EMG,
      postoperative amplitude levels of group D were significantly decreased, compared
      to preoperative amplitude levels (P=0.043). We found no statistically significant
      difference in inflammation among the groups. In none of the groups, foreign body
      reaction and granulation tissue were not detected in any of the groups. In
      addition, degeneration in axon, myelin, or perineural nets was not detected in
      any of the groups. CONCLUSION: This study results suggest that BC has no direct
      toxicity on facial nerve, while it has indirect effects, by decreasing amplitude.
      Therefore, we conclude that direct contact of BC with nerve should be avoided,
      and the area should be cleaned by aspiration or washing with physiological saline
      in case of contact.

PMID- 29587475
TI  - Microbiological Results From Middle Ear Effusion in Pediatric Patients Receiving
      Ventilation Tube Insertion: Multicenter Registry Study on the Effectiveness of
      Ventilation Tube Insertion in Pediatric Patients With Chronic Otitis Media With
      Effusion: Part I.
AB  - OBJECTIVES: The aim of this multicenter registry study was to investigate the
      effectiveness of ventilation tube insertion and the microbiology of otitis media
      with effusion (OME) in children. This part I study was conducted to evaluate the
      microbiological profile of children with OME who needed ventilation tube
      insertion. METHODS: Patients <15 years old who were diagnosed as having OME and
      received ventilation tube insertion were prospectively enrolled in 16 tertiary
      hospitals from June 2014 to December 2016. After excluding patients with missing
      data, the data of 397 patients were analyzed among a total of 433 enrolled
      patients. The clinical symptoms, findings of the tympanic membrane, hearing
      level, and microbiological findings were collected. RESULTS: In 103 patients
      (25.9%), antibiotics were used within 3 weeks before surgery. Ventilation tube
      insertion was performed in a total of 710 ears (626 in both ears in 313 patients,
      55 in the left ear only, and 29 in the right ear only). Culture of middle ear
      effusion was done in at least one ear in 221 patients (55.7%), and in a total of
      346 ears. Only 46 ears (13.3%) showed positive results in middle ear effusion
      culture. Haemophilus influenzae (17.3%, followed by coagulase-negative
      Staphylococcus and Staphylococcus auricularis) was the most common bacteria
      detected. CONCLUSION: H. influenzae was the most commonly found bacteria in
      middle ear effusion. Relatively low rates of culture positivity were noted in
      middle ear effusion of patients with OME in Korea.

PMID- 29587476
TI  - Role of the Bound Phospholipids in the Structural Stability of Cholesteryl Ester
      Transfer Protein.
AB  - Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl
      esters (CEs) from antiatherogenic high-density lipoproteins to proatherogenic low
      density lipoproteins. Inhibition of CETP is therefore being pursued as a
      potential strategy to reduce cardiovascular risk. The crystal structure of CETP
      has revealed the existence of two neutral CEs and two charged phospholipids (PLs)
      in its hydrophobic tunnel. This is in direct contrast to the other lipid-binding
      proteins that contain only two bound lipids. Moreover, previous animal studies on
      mice showed no detectable PL-transfer activity of CETP. Thus, the role of bound
      PLs in CETP is completely unknown. Here, we employ molecular dynamics simulations
      and free-energy calculations to unravel the primary effects of bound PLs on CETP
      structure and dynamics and attempt to correlate the observed changes to its
      function. Our results suggest that the structure of CETP is elastic and can
      attain different conformations depending on the state of bound PLs. In solution,
      these PLs maintain CETP in a bent-untwisted conformation that can uphold neutral
      lipids in its core tunnel. Results also suggest that although both PLs complement
      each other in their action, the C-terminal PL (C-PL) imparts greater influence on
      CETP by virtue of its tighter binding. Our finding fits very well with the recent
      inhibitor-bound CETP crystal structure, where the inhibitor displaced the N
      terminal PL for binding to CETP's central domain without disrupting the binding
      of C-PL. We speculate that the observed increased flexibility of CETP in the
      absence of PLs could play a crucial role in its binding with lipoproteins and
      subsequent lipid-transfer activity.

PMID- 29587477
TI  - S- Cis Diene Conformation: A New Bathochromic Shift Strategy for Near-Infrared
      Fluorescence Switchable Dye and the Imaging Applications.
AB  - In this paper, we present a novel charge-free fluorescence-switchable near
      infrared (IR) dye based on merocyanine for target specific imaging. In contrast
      to the typical bathochromic shift approach by extending pi-conjugation, the
      bathochromic shift of our merocyanine dye to the near-IR region is due to an
      unusual S- cis diene conformer. This is the first example where a fluorescent dye
      adopts the stable S- cis conformation. In addition to the novel bathochromic
      shift mechanism, the dye exhibits fluorescence-switchable properties in response
      to polarity and viscosity. By incorporating a protein-specific ligand to the dye,
      the probes (for SNAP-tag and hCAII proteins) exhibited dramatic fluorescence
      increase (up to 300-fold) upon binding with its target protein. The large
      fluorescence enhancement, near-IR absorption/emission, and charge-free scaffold
      enabled no-wash and site-specific imaging of target proteins in living cells and
      in vivo with minimum background fluorescence. We believe that our unconventional
      approach for a near-IR dye with the S- cis diene conformation can lead to new
      strategies for the design of near-IR dyes.

PMID- 29587478
TI  - Celecoxib Conjugated Fluorescent Probe for Identification and Discrimination of
      Cyclooxygenase-2 Enzyme in Cancer Cells.
AB  - Cyclooxygenase-2 (COX-2) is an enzyme overexpressed in most types of cancers and
      has been used for an excellent targetable biomarker. Celecoxib is an effective
      inhibitor of COX-2, used in anti-inflammation. Herein we report a one and two
      photon fluorescence probe (NP-C6-CXB) for COX-2, based on the conjugation of
      naphthalamide with Celecoxib, by using flexible hexylene linker. NP-C6-CXB is
      nonfluorescent in buffer solution and normal cells, while it shows bright
      fluorescence in solutions and cancer cells in the presence of COX-2 with an
      excellent selectivity. Interestingly, NP-C6-CXB can discriminate cancer cells
      (MCF-7) from normal cells (COS-7) in the single culture medium under confocal
      microscopy. Due to the selective binding affinity of NP-C6-CXB with a COX-2
      enzyme, the intensity is proportional to the level of COX-2 enzyme in cancer
      cells. In vivo and in vitro experiments proved that NP-C6-CXB is a potential tool
      for identification of tumor and might be used in surgical resection of COX-2
      expressed tumors.

PMID- 29587479
TI  - Novel 64Cu Labeled RGD2-BBN Heterotrimers for PET Imaging of Prostate Cancer.
AB  - Bombesin receptor 2 (BB2) and integrin alphavbeta3 receptor are privileged
      targets for molecular imaging of cancer because of their overexpression in a
      number of tumor tissues. The most recent developments in heterodimer-based
      radiopharmaceuticals concern BB2- and integrin alphavbeta3-targeting compounds,
      consisting of bombesin (BBN) and cyclic arginine-glycine-aspartic acid peptides
      (RGD), connected through short length linkers. Molecular imaging probes based on
      RGD-BBN heterodimer design exhibit improved tumor targeting efficacy compared to
      the single-receptor targeting peptide monomers. However, their application in
      clinical study is restricted because of inefficient synthesis or unfavorable in
      vivo properties, which could depend on the short linker nature. Thus, the aim of
      the present study was to develop a RGD2-BBN heterotrimer, composed of (7-14)BBN
      NH2 peptide (BBN) linked to the E[ c(RGDyK)]2 dimer peptide (RGD2), bearing the
      new linker type [Pro-Gly]12. The heterodimer E[c(RGDyK)]2-PEG3-Glu-(Pro-Gly)12
      BBN(7-14)-NH2 (RGD2-PG12-BBN) was prepared through conventional solid phase
      synthesis, then conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic
      acid (NODA-GA). In 64Cu labeling, the NODA-GA chelator showed superior
      radiochemical characteristics compared to DOTA (70% vs 40% yield, respectively).
      Both conjugates displayed dual targeting ability, showing good alphavbeta3
      affinities and high BB2 receptor affinities which, in the case of the NODA-GA
      conjugate, were in the same range as the best RGD-BBN heterodimer ligands
      reported to date ( Ki = 24 nM). 64Cu-DOTA and 64Cu-NODA-GA probes were also found
      to be stable after 1 h incubation in mouse serum (>90%). In a microPET study in
      prostate cancer PC-3 xenograft mice, both probes showed low tumor uptake,
      probably due to poor pharmacokinetic properties in vivo. Overall, our study
      demonstrates that novel RGD-BBN heterodimer with long linker can be prepared and
      they preserve high binding affinities to BB2 and integrin alphavbeta3 receptor
      binding ability. The present study represents a step forward in the design of
      effective heterodimer or heterotrimer probes for dual targeting.

PMID- 29587480
TI  - Design and Synthesis of Novel Positive Allosteric Modulators of alpha7 Nicotinic
      Acetylcholine Receptors with the Ability To Rescue Auditory Gating Deficit in
      Mice.
AB  - A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed,
      synthesized, and evaluated as the type I positive allosteric modulators of human
      alpha7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The
      structure-activity relationship analysis identified the compound 3ea as a potent
      and efficacious PAM with the maximum activation effect of the alpha7 current of
      over 1633% in the presence of acetylcholine (100 MUM) and an EC50 = 1.26 MUM. It
      is highly specific to alpha7 nAChR over other subtypes of nAChR, 5-HT3A, NMDA,
      and GABAA receptors. Compound 3ea showed an elimination half-life of 10.8 +/- 1.5
      h for 3 mg/kg, i.v., and 7.4 +/- 1.1 h for 60 mg/kg, i.g. in rat. It also
      exhibited sufficient blood-brain barrier penetration with no significant effect
      on hERG channel. Most importantly, compound 3ea dose-dependently (0.1-1 mg/kg,
      i.p.) reversed the prepulse inhibition deficit induced by MK-801 in the mouse
      schizophrenia model.

PMID- 29587481
TI  - In Vivo Bioluminescence Imaging of Cobalt Accumulation in a Mouse Model.
AB  - As a trace element nutrient, cobalt is critical for both prokaryotes and
      eukaryotes. In the current study, a turn-on Cobalt Bioluminescent Probe 1 (CBP-1)
      for the detection of cobalt has been successfully developed based on oxidative C
      O bond cleavage. This probe exhibited high selectivity and sensitivity toward
      cobalt over other analytes. By using CBP-1, the successful in vivo imaging of
      cobalt accumulation was carried out in a mouse model. Such an ability to
      determine cobalt in living animals provides a powerful technology for studying
      the system distribution, toxic potency, and biological effect of Co2+.

PMID- 29587482
TI  - Fog Harvesting with Harps.
AB  - Fog harvesting is a useful technique for obtaining fresh water in arid climates.
      The wire meshes currently utilized for fog harvesting suffer from dual
      constraints: coarse meshes cannot efficiently capture microscopic fog droplets,
      whereas fine meshes suffer from clogging issues. Here, we design and fabricate
      fog harvesters comprising an array of vertical wires, which we call "fog harps".
      Under controlled laboratory conditions, the fog-harvesting rates for fog harps
      with three different wire diameters were compared to conventional meshes of
      equivalent dimensions. As expected for the mesh structures, the mid-sized wires
      exhibited the largest fog collection rate, with a drop-off in performance for the
      fine or coarse meshes. In contrast, the fog-harvesting rate continually increased
      with decreasing wire diameter for the fog harps due to efficient droplet shedding
      that prevented clogging. This resulted in a 3-fold enhancement in the fog
      harvesting rate for the harp design compared to an equivalent mesh.

PMID- 29587483
TI  - Clustered Single Cellulosic Fiber Dissolution Kinetics and Mechanisms through
      Optical Microscopy under Limited Dissolving Conditions.
AB  - Herein, we describe a new method of assessing the kinetics of dissolution of
      single fibers by dissolution under limited dissolving conditions. The dissolution
      is followed by optical microscopy under limited dissolving conditions. Videos of
      the dissolution were processed in ImageJ to yield kinetics for dissolution, based
      on the disappearance of pixels associated with intact fibers. Data processing was
      performed using the Python language, utilizing available scientific libraries.
      The methods of processing the data include clustering of the single fiber data,
      identifying clusters associated with different fiber types, producing average
      dissolution traces and also extraction of practical parameters, such as, time
      taken to dissolve 25, 50, 75, 95, and 99.5% of the clustered fibers. In addition
      to these simple parameters, exponential fitting was also performed yielding rate
      constants for fiber dissolution. Fits for sample and cluster averages were
      variable, although demonstrating first-order kinetics for dissolution overall. To
      illustrate this process, two reference pulps (a bleached softwood kraft pulp and
      a bleached hardwood pre-hydrolysis kraft pulp) and their cellulase-treated
      versions were analyzed. As expected, differences in the kinetics and dissolution
      mechanisms between these samples were observed. Our initial interpretations are
      presented, based on the combined mechanistic observations and single fiber
      dissolution kinetics for these different samples. While the dissolution
      mechanisms observed were similar to those published previously, the more direct
      link of mechanistic information with the kinetics improve our understanding of
      cell wall structure and pre-treatments, toward improved processability.

PMID- 29587484
TI  - Experimental and Theoretical Study on Supramolecular Ionic Liquid (IL)-Asphaltene
      Complex Interactions and Their Effects on the Flow Properties of Heavy Crude
      Oils.
AB  - A combined study for understanding the molecular interactions of asphaltenes with
      molecular species such as ionic liquids (ILs) comprised experimental measurements
      and computational numerical simulation calculations, using density-functional
      theory (DFT) with dispersion corrections, molecular dynamics (MD) calculations,
      and experimental rheological characterization of the heavy crude oils (HCOs),
      before and after doping with ILs, respectively. The main results show that ILs
      influence the asphaltenic dimer association by forming supramolecular complexes
      that modify the properties of crude oils such as viscosity and interfacial
      tension. The IL-cation and asphaltene-pi ligand molecular interactions seem to
      dominate the interactions between ionic liquids and asphaltenes, where ILs' high
      aromaticity index induces a strong interaction with the aromatic hard core of
      asphaltenes.

PMID- 29587485
TI  - Wnt Signaling Activates TP53-Induced Glycolysis and Apoptosis Regulator and
      Protects Against Cisplatin-Induced Spiral Ganglion Neuron Damage in the Mouse
      Cochlea.
AB  - AIMS: Cisplatin can damage spiral ganglion neurons (SGNs) and cause sensorineural
      hearing loss. Wnt activation protects against neomycin-induced hair cell damage
      in the mouse cochlea, but the role of Wnt signaling in protecting SGNs from
      cisplatin treatment has not yet been elucidated. This study was designed to
      investigate the neuroprotective effects of Wnt signaling against cisplatin
      induced SGN damage. RESULTS: First, we found that Wnt signaling was activated in
      SGNs after cisplatin treatment. Next, we discovered that overexpression (OE) of
      Wnt signaling in SGNs reduced cisplatin-induced SGN loss by inhibiting caspase
      associated apoptosis, thus preventing the loss of SGN function after cisplatin
      treatment. In contrast, inhibition of Wnt signaling increased apoptosis, made
      SGNs more vulnerable to cisplatin treatment, and exacerbated hearing loss. TP53
      induced glycolysis and apoptosis regulator (TIGAR), which scavenges intracellular
      reactive oxygen species (ROS), was upregulated in SGNs in response to cisplatin
      administration. Wnt/beta-catenin activation increased TIGAR expression and
      reduced ROS level, while inhibition of Wnt/beta-catenin in SGNs reduced TIGAR
      expression and increased the ROS level. Moreover, OE of TIGAR reduced ROS and
      decreased caspase 3 expression, as well as increased the survival of SGNs in Wnt
      inhibited SGNs. Finally, antioxidant treatment rescued the more severe SGN loss
      induced by beta-catenin deficiency after cisplatin treatment. Innovation and
      Conclusion: This study is the first to indicate that Wnt signaling activates
      TIGAR and protects SGNs against cisplatin-induced damage through the inhibition
      of oxidative stress and apoptosis in SGNs, and this might offer novel therapeutic
      targets for the prevention of SGN injury. Antioxid. Redox Signal. 00, 000-000.

PMID- 29587486
TI  - CyberKnife radiotherapy for orbital metastases: A single-center experience on 24
      lesions.
AB  - OBJECTIVES: To evaluate the feasibility, in terms of acute toxicity and symptom
      control, of CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy
      (CyberKnife-SRT) for metastatic orbital lesions. METHODS: This retrospective
      study included patients with symptomatic metastases wholly located within the
      orbit. Palliative radiation treatment was performed using CyberKnife image-guided
      technology. Gross tumor volume was defined on a pre-radiotherapy magnetic
      resonance imaging. Acute and late toxicity was recorded according to Radiation
      Therapy Oncology Group/European Organization for Research and Treatment of Cancer
      Scale. RESULTS: Between April 2012 and July 2016, 21 patients underwent
      CyberKnife-SRT for 24 orbital metastases from different primary tumors. Median
      treatment dose was 18 Gy (15-24 Gy) given in a median of 3 fractions (2-3
      fractions) with a median dose of 6 Gy/fraction (5-10 Gy/fraction). Acute grade 1
      toxicity was observed in eight cases. No local recurrence occurred after median
      follow-up of 6.2 months (1.1-30.0 months) among 16 lesions that underwent post
      stereotactic radiotherapy magnetic resonance imaging. All patients reported
      decreasing pre-stereotactic radiotherapy symptoms without late toxicity. Follow
      up >6 months (median 22.8 months) was available for nine lesions; complete and
      partial radiological response was registered in four and five of them,
      respectively. CONCLUSION: In our experience, CyberKnife-SRT is a well-tolerated
      treatment that offers high local and symptom control in patients with intraocular
      and periocular malignant lesions.

PMID- 29587487
TI  - Retinal vascular speed <0.5 disc diameter per week as an early sign of
      retinopathy of prematurity requiring treatment.
AB  - PURPOSE: To analyse the speed of temporal retinal vascularisation in preterm
      infants included in the screening programme for retinopathy of prematurity.
      MATERIAL AND METHODS: A total of 185 premature infants were studied
      retrospectively between 2000 and 2017 in San Cecilio University Hospital of
      Granada, Spain. The method of binocular indirect ophthalmoscopy with indentation
      was used for the examination. The horizontal disc diameter was used as a unit of
      length. Speed of temporal retinal vascularisation (disc diameter/week) was
      calculated as the ratio between the extent of temporal retinal vascularisation
      (disc diameter) and the time in weeks. RESULTS: The weekly temporal retinal
      vascularisation (0-1.25 disc diameter/week, confidence interval) was
      significantly higher in no retinopathy of prematurity (0.73 +/- 0.22 disc
      diameter/week) than in stage 1 retinopathy of prematurity (0.58 +/- 0.22 disc
      diameter/week). It was also higher in stage 1 than in stages 2 (0.46 +/- 0.14
      disc diameter/week) and 3 of retinopathy of prematurity (0.36 +/- 0.18 disc
      diameter/week). The rate of temporal retinal vascularisation (disc diameter/week)
      decreases when retinopathy of prematurity stage increases. The area under the
      receiver operating characteristic curve was 0.85 (95% confidence interval: 0.79
      0.91) for retinopathy of prematurity requiring treatment versus not requiring
      treatment. The best discriminative cut-off point was a speed of retinal
      vascularisation <0.5 disc diameter/week, with a sensitivity and a specificity of
      84.8% and 77%, respectively. CONCLUSION: The rate of temporal retinal
      vascularisation is a quantifiable observation that can help to alert a clinician
      that treatment of retinopathy of prematurity may be required. However, before
      becoming a new standard of care for treatment, it requires careful documentation,
      with agreement between several ophthalmologists.

PMID- 29587488
TI  - Clinical outcomes of Ahmed glaucoma valve implantation in pediatric glaucoma.
AB  - PURPOSE: To evaluate the outcomes of Ahmed glaucoma valve implantation in
      refractory primary congenital glaucoma as well as primary procedure in aphakic
      glaucoma. METHOD: In this retrospective study, medical records of patients who
      underwent Ahmed glaucoma valve implantation for refractory glaucoma and aphakic
      glaucoma were reviewed. Primary outcome measures were the surgical success
      defined as intraocular pressure <=21 mm Hg and decreased >=20% and no secondary
      glaucoma surgery. Secondary outcome measures were the number of glaucoma
      medications, complications, best corrected visual acuity, and intraocular
      pressure. RESULTS: A total of 62 eyes of refractory primary congenital glaucoma
      patients (group 1) and 33 eyes of aphakic glaucoma patients (group 2) were
      included in our study. Mean follow-up was 51 +/- 33 months in group 1 and 49 +/-
      41 months in group 2 (p = 0.82). The cumulative probability of success was 90% in
      both groups at the first year; however, the success rate was 52.5% in group 1 and
      71.5% in group 2 at 5 years' follow-up visit. In group 1, the mean intraocular
      pressure +/- standard deviation was 33.1 +/- 8.6 mm Hg at the baseline and
      decreased to 17.1 +/- 5.3 mm Hg at 1 year and 18.5 +/- 6.4 at 3 years
      postoperatively (all p's < 0.001). Corresponding values for group 2 were 28.9 +/-
      6.1, 15.2 +/- 4.6, and 16.0 +/- 5.9 mm Hg, respectively (all p's < 0.001). The
      baseline number of glaucoma medications was 3 +/- 0.7 that decreased to 2 +/- 0.8
      at final follow-up (p = 0.02). CONCLUSION: Ahmed glaucoma valve implantation has
      a moderate success rate in the management of refractory primary congenital
      glaucoma with an increased chance of tube-related complications. The surgical
      success rate is higher in case of primary Ahmed glaucoma valve implant for
      aphakic glaucoma with acceptable safety profile.

PMID- 29587489
TI  - EB 2017 Article: Changes in advanced glycation end products, beta-defensin-3, and
      interleukin-17 during diabetic periodontitis development in rhesus monkeys.
AB  - The bidirectional relationship between diabetes mellitus (DM) and periodontal
      disease has drawn great attention; however, the mechanisms underlying their
      association remain unclear. In this study, we aimed to develop a rhesus monkey
      model of diabetic periodontitis and explore the potential mechanisms by which DM
      affects the progression of periodontal disease. Three healthy rhesus monkeys were
      selected as the control group. Five streptozotocin-induced diabetic rhesus
      monkeys were chosen as the experimental group. Ligature placement was used to
      induce periodontitis. The changes in the levels of advanced glycation end
      products (AGEs), beta-defensin-3 (BD-3), and interleukin-17 (IL-17) were measured
      using enzyme-linked immunosorbent assays (ELISA) and real-time reverse
      transcription polymerase chain reaction (RT-PCR) at different stages during
      disease progression. Periodontitis was confirmed by clinical assessment,
      radiographic images, and histological examination. Significant changes in the
      levels of AGEs and BD-3 in serum were observed at the periodontitis stage in
      diabetic rhesus monkeys ( P < 0.05). The expression of BD-3 mRNA in the gingiva
      of diabetic group at baseline was significantly high ( P < 0.05). Diabetic
      monkeys exhibited significantly enhanced IL-17 mRNA expression at the
      periodontitis stage ( P < 0.05). Our findings indicated that the rhesus monkey
      can serve as an ideal model for exploring the pathogenesis of diabetic
      periodontitis, and the hyperglycemic environment may accelerate inflammatory
      response and weaken the defense system in periodontal tissues. Impact statement
      The mechanism underlying the association between diabetes mellitus (DM) and
      periodontal disease is not yet fully understood. Hence, there is a need to
      establish animal models to reveal the effect of DM on the pathogenesis of
      periodontitis. In this study, we explored the appropriate methods for inducing
      periodontitis and shortening the modeling time in rhesus monkeys, to investigate
      the pathogenesis of diabetic periodontitis and develop innovative therapies. Our
      results suggest that a hyperglycemic environment might lead to the destruction of
      periodontal tissues by accelerating inflammatory response and weakening the
      defense system in periodontal tissues. Therefore, this study has significant
      treatment implications regarding the regulation of the immune response against
      periodontal diseases in patients with DM.

PMID- 29587490
TI  - The impact of social support and partner relationship dynamics on engagement in
      HIV care and antiretroviral treatment adherence among MSM in Latin America.
AB  - In Latin America (LA), HIV prevalence among MSM is estimated at thirty times
      greater than in the general male population. Little is known about the role of
      social support or disclosure status in relation to the HIV care continuum among
      LA MSM. Using multivariable logistic generalized estimation equations, we
      assessed the impact of social support satisfaction and disclosure status on
      engagement in HIV care, ART initiation, and ART adherence with data from an
      online, multinational sample of HIV infected MSM in Latin America (N = 2,350).
      80.0% were engaged in HIV care, 71% initiated ART, and among those, 37% reported
      missing at least one dose in the past month. In multivariable models, compared to
      being very satisfied with social support, being somewhat satisfied (aOR = 0.73,
      95% CI 0.56, 0.95) or somewhat dissatisfied (aOR = 0.83, 95% CI 0.70, 0.98) were
      associated with reduced odds of reporting 100% ART adherence. Disclosure of
      status was associated with a greater odds of HIV care engagement (OR = 1.63, 95%
      CI 1.28, 2.07) and ART initiation (OR = 1.55, 95% CI 1.30, 1.84). Greater
      satisfaction with social support and comfort disclosing HIV status to these
      sources were associated with improved engagement in HIV care and greater
      initiation of ART among MSM in LA.

PMID- 29587491
TI  - Graft-free glaucoma drainage device implantation: Short tunnel small flap
      technique.
AB  - PURPOSE: To introduce a new technique of short tunnel small flap graft-free
      glaucoma drainage device implantation and report our early experience. METHODS:
      In a retrospective study, patients with uncontrolled primary open-angle glaucoma
      underwent short tunnel small flap graft-free Ahmed glaucoma valve implantation.
      In this technique, plate is sutured 8-10 mm posterior to the limbus and a partial
      thickness flap is made at 1 or 11 o'clock position, 1 mm posterior the limbus.
      Tube was passed through a tunnel immediately anterior to the plate into the
      proximal edge of the flap and then inserted into the anterior chamber via a route
      underneath the flap. Flap then covered the distal end of the tube and conjunctiva
      was sutured. Patients were followed for a minimum of 12 months for any sign of
      tube exposure and rise of intraocular pressure. RESULTS: A total of 16
      consecutive patients with refractory primary open-angle glaucoma and uncontrolled
      intraocular pressure were included in this study. Mean age of participants was 59
      +/- 8.3 years and nine (56%) were male. Mean intraocular pressure at the time of
      presentation was 26 +/- 6.2 mm Hg, which dropped to 16 +/- 4.5 at 12 months
      postoperative follow-up. The number of medications at baseline was 3 +/- 1 eye
      drops, which was decreased to 1 +/- 1.2 at 12 months. There were no conjunctival
      and flap-related complications or any sign of tube exposure during 1-year
      postoperative period. CONCLUSION: Short tunnel small flap graft-free glaucoma
      drainage device implantation technique combines advantages of both tunneling and
      flap techniques. Also, it may result in better tube positioning and more
      favorable cosmetic outcomes.

PMID- 29587492
TI  - HIV-1 Genetic Diversity in Recently Diagnosed Infections in Moscow: Predominance
      of AFSU, Frequent Branching in Clusters, and Circulation of the Iberian Subtype G
      Variant.
AB  - HIV-1 protease-reverse transcriptase sequences from 62 HIV-1-infected individuals
      recently diagnosed in Moscow were analyzed. Subtype A former Soviet Union (FSU)
      (AFSU) variant was the predominant clade (62.9%), followed by subtype B (22.6%),
      unique recombinants (6.5%), subtype G (6.5%), and CRF01_AE (1.6%). AFSU
      predominated among people who inject drugs (88.9%) and heterosexually acquired
      infections (77.8%), while subtype B was the most prevalent genetic form among men
      who have sex with men (44%), although AFSU was also frequent in this population
      (36%). Forty-eight (77.4%) viruses branched within intrasubtype clusters, three
      of which, of subtype B, had a majority of viruses collected outside of FSU. The
      four subtype G viruses identified in this study belonged to the Portuguese
      Spanish (Iberian) variant and, together with three from databases, formed a
      Russian cluster closely related to viruses from Denmark. This is the first report
      of the circulation of the Iberian subtype G variant in Russia.

PMID- 29587493
TI  - Molecular characterization of fowl aviadenoviruses species D and E associated
      with inclusion body hepatitis in chickens and falcons indicates possible cross
      species transmission.
AB  - During the period from 2015 to 2017, frequent outbreaks of inclusion body
      hepatitis (IBH) were observed in broiler chickens and falcons in Saudi Arabia.
      Fifty samples were collected from both species. The histopathological examination
      and polymerase chain reaction confirmed the IBH infection in eight samples (five
      samples from chickens and three samples from falcons). The genomic sequence and
      phylogenetic analysis based on nucleotide and amino acid sequences of Saudi
      strains, reference fowl aviadenoviruses (FAdVs) and field viruses available in
      Genbank revealed that all investigated FAdVs clustered into FAdV-2 (species D)
      and FAdV-6 (species E). The host-dependent characterization revealed that falcon
      origin strains showed low identity (~35%) with falcon adenoviruses isolated from
      USA, which clustered into a separate group. The identification of FAdV-D and FAdV
      E in diseased falcons and chickens indicates cross-species transmission although
      falcons and chickens are phylogenetically different. The control of IBH infection
      in falcons and chickens should be based on the separation of carriers and
      susceptible chickens as well as falcons to prevent cross-species contact.
      Vaccination is an important method for prevention of IBH. The characterization of
      newly emerging FAdV strains provides valuable information for the development of
      an efficacious control strategy based on the molecular structure of current
      circulating FAdV strains in different species of birds.

PMID- 29587494
TI  - Species Dynamics in Phytoplankton Blooms: Incomplete Mixing and Competition for
      Light.
AB  - With the eutrophication of many freshwaters and coastal environments,
      phytoplankton blooms have become a common phenomenon. This article uses a
      reaction-diffusion model to investigate the implications of mixing processes for
      the dynamics and species composition of phytoplankton blooms. The model
      identifies four key parameters for bloom development: incident light intensity,
      background turbidity, water column depth, and turbulent mixing rates. The model
      predicts that the turbulent mixing rate is a major determinant of the species
      composition of phytoplankton blooms. In well-mixed environments, the species with
      lowest "critical light intensity" should become dominant. But at low mixing
      rates, the species with lowest critical light intensity is displaced if other
      species obtain a better position in the light gradient. Instead of a gradual
      change in species composition, the model predicts steep transitions between the
      dominance regions of the various species. The model predicts a low species
      diversity: phytoplankton blooms in eutrophic environments should be dominated by
      one or a few species only. The model predictions are consistent with laboratory
      competition experiments and many existing field data. We recommend examining
      competition in phytoplankton blooms under well-controlled laboratory conditions,
      and we derive scaling rules that facilitate translation from the laboratory to
      the field.

PMID- 29587495
TI  - Dispersal-Dependent Oviposition and the Aggregation of Parasitism.
AB  - The prediction that parasitoid foraging effort should increase with distance
      traversed to reach or to locate hosts has had little experimental attention.
      Consistent with a number of models of foraging behavior, we found that the per
      capita number of ovipositions by the minute fairyfly-egg parasitoid Anagrus
      sophiae increased significantly with dispersal distance to planthopper hosts in
      the field in experimental patches of many host eggs. In large continuous stands
      of cordgrass host plants, after dispersal of decimeters or less, female wasps
      laid approximately 18% of their average of 18.6 eggs. After dispersal to plants
      isolated 10 m from other cordgrass, they laid approximately 84%, and they laid
      virtually all of their eggs after dispersal of 250 m to experimental floating
      islands of cordgrass. The increased oviposition following dispersal tripled the
      CV2 index of aggregation of parasitism to a level theoretically sufficient to
      promote locally stable parasitoid-host dynamics in isolated patches. At the same
      time, the change in wasp behavior did not affect the relationship between
      parasitism and host density, which was consistently density independent. Our
      results suggest that increased foraging effort with distance traversed can
      counter Allee effects in colonization and increase spatial spread of populations
      of natural enemies.

PMID- 29587496
TI  - Adult Survival and Imperfect Assessment of Parentage: Effects on Male Parenting
      Decisions.
AB  - Applications of molecular methods to assess parentage have revealed that the
      distribution of reproductive success among individuals often differs, sometimes
      dramatically, from expectation based on observation of behavioral association.
      Much theory exists on whether and when males should reduce parental care in
      response to level of paternity. Life-history theory predicts that trade-offs in
      reproductive effort should be influenced by adult survival. We used a dynamic
      programming approach to address how level of paternity, ability to assess
      paternity, and adult survival rate interact to affect male tolerance of reduced
      parentage in a given brood. Adult survival has the greatest influence on male
      decisions such that, for any given cost of reproduction and value of male care,
      tolerance of extrapair fertilizations (EPFs) decreases as adult survival
      increases. An unexpected result of these models is that an optimal response also
      depends on a male's ability to predict probability of parentage (i.e.,
      uncertainty). These models better characterize the nature of paternity
      uncertainty and its effect on EPF tolerance than have previous models and add to
      our understanding of the complex relationship between uncertainty, mating
      strategies, and adult survival.

PMID- 29587497
TI  - A Dynamical Theory of Speciation on Holey Adaptive Landscapes.
AB  - A holey adaptive landscape is an adaptive landscape where relatively infrequent
      well-fit combinations of genes form a contiguous set that expands throughout the
      genotype space. I formulate and study a series of simple models describing the
      dynamics of speciation on holey adaptive landscapes driven by mutation and random
      genetic drift. Unlike most previous models that concentrate only on some stages
      of speciation, the models studied here describe the complete process of
      speciation from initiation until completion. The evolutionary factors included
      are selection (reproductive isolation), random genetic drift, mutation,
      recombination, and migration. In these models, pre- and postmating reproductive
      isolation is a consequence of cumulative genetic change. I study possibilities
      for speciation according to allopatric, parapatric, peripatric, and vicariance
      scenarios. The results presented here, together with earlier numerical
      simulations, strongly suggest that rapid speciation, including simultaneous
      emergence of several new species, is a plausible outcome of the evolutionary
      dynamics of subdivided populations. Rapid speciation is most likely for
      populations that are subdivided into a large number of small subpopulations.
      Speciation is possible even when subpopulations exchange several individuals per
      generation. Selection for local adaptation is not necessary for rapid speciation.
      I briefly discuss implications of the dynamics on holey adaptive landscapes for
      the nearly neutral theory of molecular evolution and for the theory of evolution
      of genetic canalization.

PMID- 29587498
TI  - Matings Systems and the Evolution of Niche Breadth.
AB  - Several theoretical studies of niche breadth evolution have shown that niche
      breadth expansion can only occur under a limited set of conditions. These studies
      have assumed that mating pairs form at random within spatial subpopulations. I
      show here that nonrandom mating within spatial subpopulations can greatly alter
      niche breadth evolution. Niche breadth expansion is restricted by assortative
      mating but is permitted by sexual selection. When new populations are formed by a
      single pulse of immigrants, the ability to persist in novel but similar
      environments is enhanced by sexual selection. When new populations receive a
      constant stream of immigrants, sexual selection allows the evolution of increased
      niche breadth even when the novel environment is very different from the
      ancestral environment. These results suggest that species lineages that exhibit
      sexual selection will have broader niches than species lineages that mate
      randomly or assortatively.

PMID- 29587499
TI  - Multiple Sexual Ornaments Coevolve with Multiple Mating Preferences.
AB  - In species where males have several ornaments for mate attraction, each ornament
      may coevolve with a different female preference. Alternatively, multiple
      ornaments may be sexually selected for because they stimulate the same, single,
      female preference. In the latter case, measures of preferences for different
      ornaments are essentially measures of the same phenotypic character and, thus,
      will be strongly pleiotropic, whereas no such expectation exists for multiple
      preferences. We selected directly up and down on two visual ornaments, orange and
      black coloration, in male guppies (Poecilia reticulata) in order to impose
      indirect selection on the female preference or preferences for these ornaments.
      Preferences for the two colors responded in a pattern similar to the response of
      the ornaments themselves. That female preferences for orange and for black in
      this guppy population are able to respond to selection more or less
      independently, suggests that they are probably two different characters in an
      evolutionary sense. Each of these preferences appears to be genetically
      correlated with the respective ornament.

PMID- 29587500
TI  - Nonequilibrium Population Dynamics of "Ideal and Free" Prey and Predators.
AB  - Aggregated spatial distributions of prey and predators promote stability of the
      otherwise unstable Nicholson-Bailey model. Nevertheless, when both predators and
      prey choose patches in an ideal free way, sufficiently aggregated distributions
      will only arise if patch quality (e.g., reflected in prey fecundity) is very
      heterogeneous. This requirement profoundly limits the possibilities for
      simultaneous population dynamical and evolutionary stability. However, stability
      is not necessary for coexistence. Under cyclic or chaotic dynamics, the rate at
      which species change their distributions becomes important. Here we consider two
      endpoints of a continuum of rates. The first is "rigid" selection of patch types
      based on the expected long-term distribution of conditions. The second is
      "flexible" selection based on current conditions. We carried out systematic
      surveys of the population-level consequences of coevolutionarily stable patch
      selection strategies for different combinations of rigid and flexible strategies
      of predator and prey. First, if both prey and predators have rigid strategies,
      the evolutionary end result is either a stable population dynamical equilibrium
      or diverging cycles eventually leading to extinction. Second, for the case with
      rigid prey and flexible predators, the persistence boundary in parameter space is
      shifted from the boundaries obtained for rigid predators. The mechanism
      underlying persistence is different in that the flexible strategies of the
      predators destabilize the equilibrium, while the evolutionary response of the
      rigid prey leads to reduced cycles. Third, if both prey and predators are
      flexible, simulations lead either to chaotic fluctuations or to extinction (but
      not to stable equilibria, nor to limit cycles), and the conditions for
      coexistence are much wider than those under rigid patch selection. These
      simulations suggest that information constraints on adaptive patch choice have a
      major impact on predator-prey persistence under nonequilibrium conditions. We
      discuss how these predictions can be tested by field observations on expansions
      and contractions in dietary range (or habitat range) in relation to population
      fluctuations.

PMID- 29587501
TI  - On Desert Rodents, Favored States, and Unresolved Issues: Scaling Up and Down
      Regional Assemblages and Local Communities.

PMID- 29587502
TI  - Assembly Rules: Desert Rodent Communities Are Structured at Scales from Local to
      Continental.

PMID- 29587503
TI  - The Diverse Effects of Intraspecific Competition on the Selective Advantage to
      Resistance: A Model and Its Predictions.
AB  - We constructed a model to investigate conditions under which intraspecific
      competition amplifies or diminishes the selective advantage to resistance. The
      growth trajectories of competing individual plants were depicted by logistic
      difference equations that incorporated basic costs (lowered growth rate) and
      benefits (lowered damage) of defense. Analytical results showed that when
      competition is absent, resistance is favored by high damage, low cost, and slow
      growth rate. Competition makes selection more complex. When herbivore damage
      reduces the size of a susceptible plant, resistant neighbors can usurp its
      resources and thus suppress its regrowth. This competitive interaction amplifies
      the relative fitness of the resistants. Numerical simulations explored a broader
      range of conditions. Three factors were varied: competition mode (symmetric vs.
      asymmetric), resistance type (damage avoidance vs. damage reduction), and timing
      of attack (early, mid, or late season). We found that competition mode had
      drastic effects on outcomes. Under symmetric competition, increased plant density
      intensified the selective advantage of resistance, damage avoidance was more
      strongly favored than damage reduction, and resistance to late attack was more
      favored than to early attack. Asymmetric competition had opposite effects:
      selection acted against resistance at high density, damage reduction was more
      strongly favored, and resistance against early attack was more favored.
      Interestingly, the two competition modes induced opposite patterns of density
      dependent selection. The difference between the symmetric and asymmetric cases is
      explained by the fact that resistance costs during the preattack phase are more
      strongly amplified by asymmetric competition. When resistance is induced, so that
      preattack costs of resistance are zero, asymmetric competition more strongly
      amplified the benefits during the postattack phase. The prediction that selection
      on resistance will be plant density-dependent has complex implications for the
      evolutionary dynamics of defense evolution.

PMID- 29587504
TI  - Population Numbers Count: Tools for Near-Term Demographic Analysis.
AB  - How do unit or proportional changes in vital rates affect populations in the
      short term? We present a new extension to standard methods of matrix model
      analysis that allows us to answer this question for the first time. By using the
      sensitivities of all the eigenvalues/vectors, rather than just the leading
      eigenvalue/vector pair, we can predict the consequences of unit or proportional
      changes in vital rates to population size and structure at any arbitrary time,
      not just when populations have neared their stable distribution. These extensions
      are particularly important in studying populations subject to frequent
      disturbance, where stable growth rate and stable distribution do not provide
      sufficient information about the effects of changes in the vital rates; managed
      populations in which short-term goals are defined; and the adequacy of the
      underlying matrix model for either short- or long-term understanding. We use
      analysis of empirical data on the cactus Coryphantha robbinsorum to demonstrate
      this approach and show that short-term predictions can differ substantially from
      those based on standard, asymptotic, analysis.

PMID- 29587505
TI  - Allocation to Mate Guarding or Increased Sperm Production in a Mediterranean
      Wrasse.
AB  - An excellent body of literature exists that examines sperm expenditure when males
      allocate only to sperm production. However, in many species, males can also
      allocate energy to behaviors that influence sperm competition. We model whether
      males in sperm competition should allocate energy to mate guarding or additional
      sperm production. Mate guarding is predicted to lead to greater reproductive
      success than increased sperm output, and mate-guarding males are not predicted to
      alter their allocation to sperm production with increasing sperm competition.
      Only when mate guarding is ineffective or greatly reduces sperm production are
      males predicted to allocate to sperm production. In a Mediterranean wrasse
      Symphodus ocellatus, three male alternative reproductive behaviors coexist. While
      nesting males and satellites guard mates to decrease sperm competition, sneaker
      males only compete via sperm production. Sneakers produce four times as much
      sperm per spawn as either nesting males or satellites. As predicted by the model,
      mate guarding but not sperm production increased with increased risk of sperm
      competition in nesting males. We argue that this can be explained by nesting
      males allocating to mate guarding rather than sperm production. Considering
      allocation among behaviors that affect sperm competition enhances our ability to
      explain and to predict sperm allocation patterns.

PMID- 29587506
TI  - Geometrical Games between a Host and a Parasitoid.
AB  - Avoiding detection by parasitoids is nearly impossible for most leafminers in
      their visually striking mines, and they often suffer from a high mortality rate
      by a great variety of parasitoid species. The leafminer-parasitoid interaction
      bears a strong resemblance to the princess-monster game developed in game theory,
      in which a "monster" (parasitoid) selects an optimal search strategy to capture
      the "princess" (leafminer), while the princess selects an optimal strategy to
      hide from the monster. This article attempts to illustrate and to quantify the
      additional complexity that occurs when the princess can modify the arena in which
      the monster searches. Feeding activity of the leafminer Phyllonorycter malella
      creates feeding windows, which are spots on the mine. Its main parasitoid
      Sympiesis sericeicornis is able to insert its ovipositor only through these
      feeding windows. Parasitism risk depends both on the leafminer-feeding pattern,
      which determines the structure of the arena in which the parasitoid searches, and
      on the position of the leafminer within the mine. The adaptive value of observed
      patterns of mine development and leafminer behavior is evaluated by comparing
      them to predictions from a simulation model of random patterns and leafminer
      positions. The leafminer creates a heterogeneous environment by leaving a central
      area of uneaten tissue. This area acts as a protecting shield and greatly
      diminishes the risk of parasitism. Hence, by controlling the structure of the
      arena in which the princess-monster game is played, the leafminer defines some of
      the rules of the game.

PMID- 29587507
TI  - Lower Species Richness in Dioecious Clades.
AB  - Despite the extensive research on the potential benefits of dioecy to
      individuals, little is known about the long-term success of dioecious lineages in
      relation to their hermaphroditic or monoecious relatives. This study reports on
      the evolutionary success of worldwide dioecious flora in light of recent
      phylogenetic work by performing sister-group comparisons of species richness
      between clades of angiosperms with different breeding systems. Whether this
      analysis is performed at the family or genus level, species richness is generally
      far lower in dioecious taxa when compared to their hermaphroditic or monoecious
      sister taxa. Despite the advantages of avoiding inbreeding depression and of
      allocating resources separately to male and female function, dioecy in
      angiosperms does not appear to be a key innovation promoting evolutionary
      radiation. A potential explanation for the low representation of dioecious
      lineages is that dioecious plants may have lower colonization rates. Baker's Law
      states that self-compatible lineages will have higher rates of successful long
      range dispersal since they do not require a mate; consequently, self-compatible
      lineages may have higher rates of allopatric speciation. However, identical
      analyses performed with hermaphroditic self-incompatible angiosperms did not
      produce similar results, suggesting that Baker's law is not the reason for the
      poor representation of dioecy among angiosperm species.

PMID- 29587508
TI  - Extinction Thresholds and Metapopulation Persistence in Dynamic Landscapes.
AB  - Models of metapopulations have focused on the effects of extinction and
      colonization rate upon metapopulation persistence and dynamics, assuming static
      landscapes wherein patches are neither created nor go extinct. However, for
      species living in ephemeral (patchy) habitats, landscapes are highly dynamic
      rather than static. In this article, we develop a lattice metapopulation model,
      of the patch occupancy type, based on interacting particle systems that
      incorporate explicitly both metapopulation and patch dynamics. Under this
      scenario, we study the effects of different regimes of patch dynamics upon
      metapopulation persistence. We analyze the lattice behavior by numerical
      simulations and a mean field approximation (MF). We show that metapopulation
      persistence and extinction are strongly influenced by the rate at which the
      landscape changes, in addition to the amount of habitat destroyed. We derive MF
      analytical expressions for extinction thresholds related to landscape properties
      such as habitat suitability and patch average lifetime. Using numerical
      simulations, we also show how these thresholds are quantitatively overestimated
      by the MF equations, although the qualitative behavior of the spatial model is
      well explained by the MF when the array of habitat patches is dynamic or static
      but connected in space and time. The implications for conservation are also
      discussed.

PMID- 29587509
TI  - Scaling Down: On the Challenge of Estimating Abundance from Occurrence Patterns.

PMID- 29587510
TI  - Reproductive Isolation Mechanism Resulting from Resolution of Intragenomic
      Conflict.
AB  - Crosses have revealed the species-specific, positively correlated intensities of
      paternally expressed growth enhancer (GE) and maternally expressed growth
      suppressor (GS), which serve as a reproductive isolation mechanism in many plants
      and animals. However, how this mechanism evolved has remained unanswered. A
      dynamic model shows that the conflict between paternally and maternally inherited
      genomes may drive them to an evolutionary "arms race" of their GE and GS
      productions, respectively. This results in paternally expressed GE and maternally
      expressed GS, and their evolutionarily stable intensities are both decreasing
      functions of species-specific degree of paternity and GE and GS production costs,
      thereby establishing a mechanism for postzygotic isolation.

PMID- 29587511
TI  - Estimating Species Abundance from Occurrence.

PMID- 29587512
TI  - The Effect of Parasites on Host Population Density and Extinction: Experimental
      Epidemiology with Daphnia and Six Microparasites.
AB  - Parasites have been shown to reduce host density and to induce host population
      extinction in some cases but not in others. Epidemiological models suggest that
      variable effects of parasites on individual hosts can explain this variability on
      the population level. Here, we aim to support this hypothesis with a specific
      epidemiological model using a cross-parasite species approach. We compared the
      effect of six parasites on host fecundity and survival to their effects on
      density and risk of extinction of clonal host populations. We contrast our
      empirical results of population density with predictions from a deterministic
      model and contrast our empirical results of host and parasite extinction rates
      with those predicted by a stochastic model. Five horizontally transmitted
      microparasites (two bacteria: white bacterial disease, Pasteuria ramosa; two
      microsporidia: Glugoides intestinalis, Ordospora colligata; one fungus:
      Metschnikowiella biscuspidata); and six strains of a vertically transmitted
      microsporidium (Flabelliforma magnivora) of the planktonic crustacean Daphnia
      magna were used. In life table experiments, we quantified fecundity and survival
      in individual parasitized and healthy hosts and compared these with the effect of
      the parasites on host population density and on the likelihood of host population
      extinction in microcosm populations. Parasite species varied strongly in their
      effects on host fecundity, host survival, host density reduction, and the
      frequency with which they drove host populations to extinction. The fewer
      offspring an infected host produced, the lower the density of an infected host
      population. This effect on host density was relatively stronger for the
      vertically transmitted parasite strains than for the horizontally transmitted
      parasites. As predicted by the stochastic simulations, strong effects of a
      parasite on individual host survival and fecundity increased the risk of host
      population extinction. The same was true for parasite extinctions. Our results
      have implications for the use of microparasites in biological control programs
      and for the role parasites play in driving small populations to extinction.

PMID- 29587513
TI  - Allometric Slopes and Independent Contrasts: A Comparative Test of Kleiber's Law
      in Primate Ranging Patterns.
AB  - At the most fundamental level, the size of an animal's home range is determined
      by its energy needs. In the absence of confounding variables, home range size
      should therefore scale with body mass according to Kleiber's exponent for
      metabolic rate of 0.75. Comparative studies in a wide range of taxa have failed
      to confirm this prediction: home range size has commonly been found to scale with
      an exponent significantly >0.75. We develop a comparative measure of metabolic
      needs that incorporates both mass-specific metabolic rate and social-group size.
      We test the prediction that home range size in primates scales isometrically with
      this measure when an appropriate linear model is applied to data corrected for
      phylogenetic bias. Analyses using species values as data points indicate an
      exponent consistent with Kleiber's law. This result is misleading, however,
      because ecological factors confound the analysis, and the slopes within some
      ecologically homogeneous taxa are steeper. Accordingly, in analyses based on
      independent contrasts with reduced major axis, slopes are significantly greater
      than predicted by Kleiber's law. We examine the effects of other variables, and
      we find that systematic variation in substrate use, home range overlap, and diet
      account for the steeper than expected relationship between home range size and
      metabolic needs based on Kleiber's law. We therefore conclude that the scaling of
      home range size is subject to Kleiber's law but in combination with other
      factors. These results emphasize that the study of allometry requires detailed
      attention to statistical models and control of confounding variables.

PMID- 29587514
TI  - Rensch's Rule Crosses the Line: Convergent Allometry of Sexual Size Dimorphism in
      Hummingbirds and Flower Mites.
AB  - Hummingbirds demonstrate the full scope of Rensch's rule (females larger than
      males in small species, males larger than females in large species). The phoretic
      flower mites that hummingbirds compete with for nectar show the same pattern. An
      analysis of phylogenetically independent contrasts for 154 hummingbird and 37
      mite species confirmed that both small (female-larger) and large (male-larger)
      species contribute to this result. I propose a common cause for this convergent
      pattern of sexual size dimorphism, with support from ecological and behavioral
      data for both groups. When morphology or behavior constrains each species to a
      limited range of resource densities, natural selection tends to diversify body
      size among species. If mating is promiscuous or polygynous, sexual selection
      favors larger males when resources are sufficient. But if male reproductive
      behavior is energetically costly, smaller males may have an advantage when
      resources are limiting, producing a pattern of allometry for sexual size
      dimorphism that conforms with Rensch's rule. Stabilizing selection on female
      size, if it occurs, amplifies this pattern. When the resource-density spectrum is
      broad enough, both female-larger and male-larger size dimorphism should occur
      within the same clade.

PMID- 29587515
TI  - Biodiversity, Stability, and Productivity in Competitive Communities.
AB  - Three markedly different models of multispecies competition-one mechanistic, one
      phenomenological, and one statistical-all predict that greater diversity
      increases the temporal stability of the entire community, decreases the temporal
      stability of individual populations, and increases community productivity. We
      define temporal stability as the ratio of mean abundance to its standard
      deviation. Interestingly, the temporal stability of entire communities is
      predicted to increase fairly linearly, without clear saturation, as diversity
      increases. Species composition is predicted to be as important as diversity in
      affecting community stability and productivity. The greater temporal stability of
      more diverse communities is caused by higher productivity at higher diversity
      (the "overyielding" effect), competitive interactions (the "covariance" effect),
      and statistical averaging (the "portfolio" effect). The relative contribution of
      each cause of temporal stability changes as diversity increases, but the net
      effect is that greater diversity stabilizes the community even though it
      destabilizes individual populations. This theory agrees with recent experiments
      and provides a degree of resolution to the diversity-stability debate: both sides
      of the longstanding debate were correct, but one addressed population stability
      and the other addressed community stability.

PMID- 29587516
TI  - Surgical Treatment of Sinus Tracts and Fistulas in Perianal Hidradenitis
      Suppurativa.

PMID- 29587517
TI  - Lipodystrophy in a Type 1 Diabetic Woman.

PMID- 29587519
TI  - 'Rex noster insanit'.

PMID- 29587518
TI  - Prospective Controlled Trial for the Treatment of Acne Keloidalis Nuchae With a
      Long-Pulsed Neodymium-Doped Yttrium-Aluminum-Garnet Laser.
AB  - BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with
      limited interventions of both high efficacy and low morbidity. OBJECTIVE: To
      assess the efficacy of the long-pulsed 1064-nm neodymium-doped yttrium-aluminum
      garnet (Nd:YAG) laser and topical steroids as a treatment for AKN compared to
      topical steroids alone. METHODS: We conducted a single-blinded, randomised,
      within-patient right-left controlled trial (n = 13). Eight monthly laser
      treatments were performed on the treated half of the scalp, and triamcinolone
      0.1% cream was applied to both sides twice daily. Treatment response was measured
      using a global assessment score (0 to 10). RESULTS: The laser-treated side showed
      greater improvement in global assessment score. The mean change was -3.2 (-49.2%)
      on the treated side and -2.2 (-32.8%) on the control side ( P = .144). Papules
      responded well to laser treatment, while larger plaques and nodules showed
      limited improvement. In the 10 patients with papules only, the difference in
      improvement between the treated and control sides was statistically significant
      (mean change was -3.5 [-59.3%] for the treated side and -1.8 [-29.5%] for the
      control side, P = .031). LIMITATIONS: This study was limited by a small sample
      size and a high dropout rate, as well as the lack of a standardised scoring
      system for AKN. CONCLUSION: The long-pulsed Nd:YAG laser in conjunction with
      topical steroids shows promising results in the treatment of AKN, particularly
      the papular component, and is well tolerated by patients.

PMID- 29587520
TI  - The Use of Humor in Palliative Care: A Systematic Literature Review.
AB  - BACKGROUND: Humor has its own place in the context of medicine. Nevertheless, its
      acceptance by terminal stage patients and health-care professionals has not been
      studied in depth and is not free from controversy. OBJECTIVES: To understand the
      significance, appropriateness, and pertinence of the use of humor in palliative
      care and to analyze its applicability. DESIGN: A narrative systematic review was
      undertaken and included in PROSPERO. DATA SOURCES: Online searches were carried
      out on PUBMED, PSYCINFO, EBSCO (CINHAL), EMBASE, SCIELO, SCOPUS, TESEO, WEB of
      SCIENCE, and COCHRANE between their launch date and December 31, 2015,
      complemented with manual searches with queries to experts. A total of 156 studies
      were identified, which were then filtered in pairs by means of an established
      hierarchy, selecting studies that discussed the use of humor specifically in
      palliative care from all perspectives and designs, and finally published in
      Spanish, English, French, or Portuguese. Critical reading of all the selected
      studies took place, with no exclusions due to quality evaluation. RESULTS: Thirty
      four studies were included. Five main topics were identified: (1) definition of
      humor, (2) use and functions of humor in palliative care, (3) how to use humor,
      (4) when not to use humor, and (5) humor before and after the diagnosis of
      terminal illness. CONCLUSIONS: Humor plays an unquestionable role in palliative
      care, but its use needs training and appropriate use.

PMID- 29587521
TI  - Orthotopic heart transplantation in children.
AB  - Heart transplantation is a relatively infrequent but technically demanding
      procedure in pediatric cardiac surgery. Orthotopic heart transplantation is often
      offered to older children or adolescents following multiple previous operations,
      but with advances in intensive care, diagnostics, and management, more infants
      with complex congenital heart diseases are being listed for transplantation.
      Primary cardiomyopathies remain the most common indication. Outcomes following
      cardiothoracic transplantation have improved steadily in recent times. Donor
      availability has been helped by increasing public awareness and donation after
      cardiac death, especially of lungs, increasing the number of patients benefiting
      from heart and/or lung transplantation. While there are still insufficient donors
      to meet the current needs, effective devices to bridge patients to
      transplantation are now widely used. Although the many advances have improved the
      outlook of transplantation, there are still difficulties that have not changed
      over time. Nevertheless, heart transplantation in children carries a reasonably
      good survival rate over the entire spectrum of recipient heart conditions. We
      discuss the salient features of acceptance of an organ and the technical aspects
      of both simple and complex heart transplantation in children.

PMID- 29587522
TI  - Surgical treatment of pulmonary metastasis: report from a tertiary care center.
AB  - Objective This retrospective analysis aimed to determine the factors influencing
      prognosis in adult patients who presented to our thoracic surgery service with
      lung metastases and were eligible for pulmonary metastasectomy. Methods We
      retrospectively reviewed the data of 296 patients who underwent resection of 575
      lung metastases from January 2000 to January 2016. Univariate and multivariate
      analyses were performed based on age, sex, histology of the primary tumor,
      disease-free interval, number and size of metastases. Results Sixty-eight
      (22.97%) patients developed lung metastases from bone sarcoma, 68 (22.97%) from
      soft-tissue sarcoma, 56 (18.9%) from head and neck cancers, 46 (15.5%) from
      colorectal cancer, and 58 (19.6%) from other epithelial tumors. The mean size of
      the lung nodules was 2.48 cm. Open surgical resection was performed in 217
      (73.3%) patients. After a mean follow-up of 43 months, 120 (40.7%) patients had
      died or were lost to follow-up. Univariate analysis confirmed that patients with
      bone cancer, soft tissue sarcoma, or colorectal carcinoma had a worse prognosis (
      p = 0.0003). Moreover, those with a disease-free interval >24 months had a better
      5-year survival ( p = 0.0001). The number and size of metastases, age, and sex
      had no effect on prognosis. The actuarial survival after complete metastasectomy
      was 71.6% (95% confidence interval: 66-75) at 2 years and 59.3% (95% confidence
      interval: 56-64) at 5 years. Conclusions Pulmonary metastasectomy provides good
      long-term survival. The type of primary tumor and disease-free interval are
      independent prognostic factors for survival.

PMID- 29587523
TI  - Assessment of electrocardiographic criteria of left atrial enlargement.
AB  - Background Left atrial enlargement is considered to be a robust, strong, and
      widely acceptable indicator of cardiovascular outcomes. Echocardiography is the
      gold standard for measurement of left atrial size, but electrocardiography can be
      simple, cost-effective, and noninvasive in clinical practice. This study was
      undertaken to assess the diagnostic accuracy of an established
      electrocardiographic criterion for left atrial enlargement, taking 2-dimensional
      echocardiography as the gold-standard technique. Methods A cross-sectional study
      was conducted on 146 consecutively selected patients with the complaints of
      dyspnea and palpitation and with a murmur detected on clinical examination, from
      September 10, 2016 to February 10, 2017. Electrocardiography and echocardiography
      were performed in all patients. Patients with a negative P wave terminal force in
      lead V1 > 40 ms.mm on electrocardiography or left atrial dimension > 40 mm on
      echocardiography were classified as having left atrial enlargement. Sensitivity
      and specificity were calculated to assess the diagnostic accuracy. Results Taking
      2-dimensional echocardiography as the gold-standard technique,
      electrocardiography correctly diagnosed 68 patients as positive for left atrial
      enlargement and 12 as negative. The sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of electrocardiography for left
      atrial enlargement were 54.4%, 57.1%, 88.3%, 17.4%, and 54.8%, respectively.
      Conclusion The electrocardiogram appears to be a reasonable indicator of left
      atrial enlargement. In case of nonavailability of echocardiography,
      electrocardiography can be used for diagnosis of left atrial enlargement.

PMID- 29587524
TI  - Acute retrograde type A intramural hematoma treated with an endovascular
      approach.
AB  - A 71-year-old woman was admitted with sudden onset of severe chest pain. Computed
      tomography demonstrated acute type A intramural hematoma with an entry tear in
      the first part of the descending aorta. The patient refused an operation.
      Endovascular repair was performed to prevent conversion to a typical dissection
      of the ascending aorta. At the 1-year follow-up, computed tomography showed total
      resolution of the intramural hematoma.

PMID- 29587525
TI  - Angiographic aspect of longstanding Starr-Edwards valve for type C Ebstein
      anomaly.

PMID- 29587526
TI  - Ocular manifestations of Marfan syndrome in children and adolescents.
AB  - PURPOSE: To study ocular manifestations of Marfan syndrome in children and
      adolescents. METHODS: Retrospective comparative cohort study on consecutive
      patients up to age 17 years, presenting to the interdisciplinary Marfan clinic of
      Charite-University Medicine Berlin over a period of 4 years. RESULTS: A total of
      52 Marfan syndrome patients and 73 controls were enrolled. In Marfan syndrome
      eyes, the cornea was flatter (mean keratometry, 40.86 +/- 2.13 vs 42.55 +/- 1.55
      diopters in control eyes, p < .001) and corneal astigmatism was greater (1.50 +/-
      1.22 vs 0.88 +/- 0.49 diopters in control eyes, p < .001). The central cornea was
      thinner in Marfan syndrome eyes (537.35 +/- 40.64 vs 552.95 +/- 38.57 MUm, p =
      0.007) and Marfan syndrome eyes were more myopic than control eyes (spherical
      equivalent, -2.77 +/- 4.77 vs -0.64 +/- 1.92 diopters, p < .001). Visual acuity
      was reduced (logMAR 0.11 +/- 0.17 vs 0.04 +/- 0.26, p = 0.014) and intraocular
      pressure was lower in Marfan syndrome eyes. Iris transillumination defects were
      more common in Marfan syndrome eyes (19.6% vs 4.3% in control eyes, odds ratio
      for Marfan syndrome in the presence of iris transillumination defects = 7.2).
      Ectopia lentis was only found in Marfan syndrome eyes (25 Marfan syndrome
      patients, 49% with available data, bilateral in 68%). CONCLUSION: Iris
      transillumination defects and ectopia lentis are characteristic ocular findings
      in children and adolescents with Marfan syndrome. Myopia is more common and
      corneal curvature, central corneal thickness, and visual acuity are reduced in
      Marfan syndrome eyes. Children with Marfan syndrome need regular comprehensive
      eye examinations to identify potential complications.

PMID- 29587527
TI  - Synthesis and antiproliferative activities of thioxoflavonoids on three human
      cancer cells.
AB  - Two series of fifteen novel thioxoflavonoids 2a-2h and 4a-4g were synthesized
      from corresponding flavonoids 1a-1h and 3a-3g by reacting with Lawesson's
      reagent, respectively. Their in vitro antiproliferative activities were evaluated
      on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) using
      cell counting kit-8 (CCK-8) assay. The results showed that most of the target
      compounds exhibited moderate to good antiproliferative activities against the
      three human cancer cell lines. In particular, thioxoflavonoids 2f and 2g showed
      the strongest antiproliferative activity on all three human cancer cell lines
      with IC50 values ranging from 3.34 to 4.67 MUM, 4f showed the best
      antiproliferative activity on Hela cells (IC50 2.30 MUM), 2e showed the best
      antiproliferative activity on HCC1954 cells (IC50 2.13 MUM) and SK-OV-3 cells
      (IC50 2.33 MUM). The antiproliferative activities may be involved in their
      antioxidant activity, which can be speculated by their ability to scavenge free
      radicals and by their capacity of affecting key redox enzymes.

PMID- 29587528
TI  - Diet-dependent changes in the intestinal DNA methylome after introduction of
      enteral feeding in preterm pigs.
AB  - AIM: To examine how enteral feeding affects the intestinal epigenome and gene
      expression just after preterm birth. MATERIALS & METHODS: Intestinal tissue from
      preterm pigs, modeling preterm infants, was collected at birth and 5 days after
      gradual introduction of infant formula or bovine colostrum. The intestinal tissue
      was analyzed by reduced representation bisulfite sequencing and real-time qPCR.
      RESULTS: Relative to colostrum, formula increased bacterial epithelial adherence
      and lipopolysaccharide binding protein (LBP) expression, which was regulated by
      promoter methylation. Diet-dependent changes in DNA methylation and/or mRNA
      expression were related to innate immune response, hypoxia, angiogenesis and
      epithelial-mesenchymal transition pathways (e.g., TTC38, IL8, C3, HIF1A and
      VEGFR1). CONCLUSION: Epigenetic changes may mediate important effects of the
      first feeding on intestinal development in preterm neonates.

PMID- 29587529
TI  - Laceioside, a new cycloartane saponin from Astragalus tephrosioides Boiss. var.
      lacei (Ali) Kirchoff.
AB  - Phytochemical investigation of the aerial parts of Astragalus tephrosioides
      Boiss. var. lacei (Ali) Kirchoff. (Family Fabaceae) resulted in the isolation of
      a new cycloartane glycoside laceioside (1). The structure of the previously
      undescribed compound 1 was established as 16beta-acetyloxy-3-O-beta-d
      glucopyranosyloxy-cycloartan-11alpha,24xi, 25-triol. The structure elucidation of
      compound 1 was based primarily on 1D and 2D-NMR techniques including 1H and
      13CNMR spectra, DEPT and by 2D COSY, HSQC and HMBC experiments.

PMID- 29587530
TI  - A multilevel examination of sleep, depression, and quality of life in people
      living with HIV/AIDS.
AB  - Sleep problems are prevalent in people living with HIV/AIDS; however, few studies
      examine how poor sleep affects mental health and quality of life longitudinally.
      A sample of people living with HIV/AIDS from a randomized trial ( N = 240; mean
      age = 47.18; standard deviation = 8.3; 71.4% male; 61.2% White) completed
      measures of depression (Montgomery-Asberg Depression Rating Scale), health
      related quality of life (AIDS Clinical Trial Group Quality of Life Measure), and
      life satisfaction (Quality of Life Inventory) at baseline and 4, 8, and 12
      months. Controlling for time, condition, and relevant interactions, sleep
      problems significantly predicted worse outcomes over time ( ps < 0.001). Findings
      have implications for the importance of identifying and treating sleep problems
      in people living with HIV/AIDS to improve mental health and quality-of-life
      outcomes.

PMID- 29587531
TI  - Learning Curves and Timing of Surgical Trials: Robotic Kidney Transplantation
      with Regional Hypothermia.
AB  - PURPOSE: Outcomes of surgical procedures can be affected by multiple factors
      including surgical skill and learning curve (LC). These factors need to be
      considered for optimal timing of surgical trials. We used the LC cumulative
      summation (CUSUM) method to describe the number of cases associated with
      competency of a single surgeon learning the technique of robotic kidney
      transplantation (RKT). METHODS: Thirty-three patients underwent Vattikuti Urology
      Institute technique of RKT at a center that recently adopted this procedure
      (study group). Anastomoses times and short-term functional outcomes were compared
      with an established RKT program (reference group). LCs were evaluated using CUSUM
      analysis using target values from the reference group. RESULTS: Mean +/- standard
      deviation for console time, rewarming time (RWT), arterial anastomosis, venous
      anastomosis, and ureterovesical anastomosis times for the study group was 187 +/-
      34.6 minutes, 58.03 +/- 17.81 minutes, 19.36 +/- 5.91 minutes, 21.97 +/- 6.78
      minutes, and 22.55 +/- 4.24 minutes, respectively, significantly longer than
      reference group (p < 0.001 for all). Mean +/- standard deviation for serum
      creatinine at discharge and 1 month in the study group was 1.43 +/- 0.57 mg/dL
      and 1.23 +/- 0.35 mg/dL, respectively, similar to the reference group (p = 0.074
      at discharge and p = 0.163 at 1 month). The LC was short, with competence
      achieved for RWT within 9, proficiency within 16, and mastery within 21 cases.
      Longer anastomosis times during the LC did not affect graft function.
      CONCLUSIONS: The LC of RKT is short, with improving skill up to 20-25 cases. The
      procedure is reproducible by surgeons experienced with open transplant and
      robotic surgery for other procedures, with comparable outcomes and low
      complication rates at a new center during adoption.

PMID- 29587532
TI  - An audit of the accuracy of medication information in electronic medical
      discharge summaries linked to an electronic prescribing system.
AB  - BACKGROUND: Poor communication of medication information to general practitioners
      when patients are discharged from hospital is a widely recognised problem. There
      has been little research exploring the accuracy of medication information in
      electronic discharge summaries (EDS) linked to hospital e-prescribing systems.
      OBJECTIVE: To evaluate the accuracy of medication lists and medication change
      information in EDS produced using an integrated e-prescribing and EDS system
      (where EDS discharge medication lists were imported from discharge e-prescription
      records, medication change information was manually entered, and medications were
      dispensed from paper copies of the patients' e-prescriptions). METHOD:
      Retrospective audit of EDSs for a random sample, representative of adult patients
      ( n = 87) discharged from a major teaching hospital. EDS medication lists were
      compared to pharmacist-verified paper discharge prescriptions (considered to be
      the most accurate discharge medication list) to identify discrepancies. EDS
      medication change information was compared to medication changes identified by
      comparing pharmacist-verified "Medication History on Admission" forms with
      pharmacist-verified paper discharge prescriptions. RESULTS: There were 85/87
      (98%) EDSs that included a discharge medication list. Of these, 50/85 (59%)
      contained one or more medication list discrepancies (median 1, range 0-15). The
      most common discrepancy was omission of medication (58%); 84/131 (64%)
      discrepancies were considered clinically significant (risk of adverse outcome);
      162/351 (46%) clinically significant medication changes were stated in the EDS;
      and 153/351 (44%) changes were both stated and included a reason. CONCLUSION: EDS
      discrepancies were common despite integration with e-prescribing. Eliminating
      paper prescriptions, enhancing e-prescribing/EDS functionality and involving
      pharmacists in EDS preparation may reduce discrepancies.

PMID- 29587533
TI  - A new triterpenoid saponin and a diterpene glucoside from the seeds of
      Orychophragmus violaceus.
AB  - One new triterpenoid saponin orychoside A (1) and one new diterpene glucoside
      orychoside B (12), together with eleven known compounds, were isolated from the
      seeds of Orychophragmus violaceus. The structures of the new compounds were
      elucidated on the basis of spectroscopic analysis. The known compounds were
      identified by comparison with data reported in the literature. All compounds were
      tested for their cytotoxic activities against the HepG2 and A549 cell lines in
      vitro. The new compound 1 exhibited potent cytotoxicity against the two cell
      lines with IC50 values of 7.13 and 8.77 MUM, respectively. Compounds 2, 5, 8 and
      9 were found to possess obvious cytotoxicity.

PMID- 29587535
TI  - Contact or Noncontact Laser Lithotripsy? (From: Tracey J, Gagin G, Morhardt D, et
      al. J Endourol 2018;32:290-295).

PMID- 29587536
TI  - Letter to the editor: On plurality and authorship in science.
AB  - Moffatt argues that the "plurality of distinct accounts of scientific authorship"
      necessitates caution in attempts to identify unethical authorship practices, and
      urges that considerations be given to establishing a "single consensus account of
      authorship." The revised International Committee of Medical Journal Editors
      (ICMJE) criteria do capture the essential features of authorship in terms of
      "intellectual contribution" and "responsibility and accountability," which would
      clearly demarcate academically legitimate authorship from the common misdemeanors
      of ghost writing and honorary authorship. However, plurality in the practice of
      science and credit-sharing culture at the ground would likely render universal
      adoption or compliance of a single consensus account of authorship untenable.

PMID- 29587534
TI  - Hypomethylation of GRHL3 gene is associated with the occurrence of neural tube
      defects.
AB  - AIM: To investigate the relationship between GRHL3 methylation and the etiology
      of neural tube defects (NTDs). MATERIALS & METHODS: Analyze data from a genome
      wide DNA methylation array. Targeted DNA methylation analysis was performed for
      46 cases and 23 controls. At last, grhl3 overexpression and gene depletion
      experiments were conducted in zebrafish. RESULTS: Five hypomethylated CpGs were
      discovered in the methylation arrays performed on NTD cases. In a validation
      study, 15 hypomethylated CpGs were found and the overall methylation levels
      decreased in brain/spinal cord tissue from NTD cases. The knockdown and
      overexpression of grhl3 in zebrafish damaged embryonic convergent extension
      processes. CONCLUSION: Hypomethylation of GRHL3 in central nervous tissue is
      associated with NTDs, further supporting the importance of GRHL3 and methylation
      in proper neural tube closure.

PMID- 29587537
TI  - Preliminary Porcine In Vivo Evaluation of a Telerobotic System for Transurethral
      Bladder Tumor Resection and Surveillance.
AB  - INTRODUCTION: Transurethral resection of bladder tumors (TURBTs) can be a
      challenging procedure, primarily due to limitations in tooltip dexterity,
      visualization, and lack of tissue depth information. A transurethral robotic
      system was developed to revolutionize TURBTs by addressing some of these
      limitations. The results of three pilot in vivo porcine studies using the novel
      robotic system are presented and potential improvements are proposed based on
      experimental observations. MATERIALS AND METHODS: A transvesical endoscope with a
      mounted optically tracked camera was placed through the bladder of the swine
      under general anesthesia. Simulated bladder lesions were created by injecting
      HistoGel processing gel mixed with blue dye, transabdominally, into various
      locations in the bladder wall under endoscopic visualization. A 7-degree-of
      freedom (DoF) robot was then used for transurethral resection/ablation of these
      simulated tumors. An independent 2-DoF distal laser arm (DLA) was deployed
      through the robot for laser ablation and was assisted by a manually controlled
      gripper for en bloc resection attempts. RESULTS: Lesions were created and ablated
      using our novel endoscopic robot in the swine bladder. Full accessibility of the
      bladder, including the bladder neck and dome, was demonstrated without requiring
      bladder deflation or pubic compression. Simulated lesions were ablated using the
      holmium laser. En bloc resection was demonstrated using the DLA and a manual
      grasper. CONCLUSION: Feasibility of robot-assisted en bloc resection was
      demonstrated. Main challenges were lack of depth perception and visual occlusion
      induced by the transvesical endoscope. Recommendations are given to enhance robot
      assisted TURBTs. Lessons learned through these pilot swine studies verify the
      feasibility of robot-assisted TURBTs while informing designers about critical
      aspects needed for future clinical deployment.

PMID- 29587538
TI  - Conducting participatory photography with children with disabilities: a
      literature review.
AB  - PURPOSE: This review summarized studies that used participatory photography with
      children with disabilities, including those with communication impairments, and
      described modifications made to the methodology to facilitate their participation
      in qualitative research. METHODS: In the fall of 2016, we searched Psycinfo
      (OVID), ERIC, CINAHL and Web of Science to identify studies that used
      participatory photography with children with disabilities. The search was
      repeated in January 2018 to retrieve any new publications. The first author
      extracted data that described the characteristics of each study and the
      modifications used. RESULTS: Of the 258 articles identified, 19 met inclusion
      criteria. Participants ranged from 4-21 years old and had a variety of
      disabilities. Study topics included education, leisure activities and adulthood.
      Researchers modified participatory photography to enhance accessibility by:
      modifying cameras; providing individual training; teaching consent through role
      play; allowing children to direct adults to take photographs; including
      additional forms of media; using diaries and questionnaires; providing individual
      interviews with simplified questions; using multiple forms of communication; and
      modifying how photographs are shared. CONCLUSIONS: Participatory photography can
      be an effective method for studying the lived experiences of children with
      disabilities, particularly those with communication impairments. Methodological
      modifications can enhance the accessibility of this approach for this population.
      Implications for Rehabilitation Participatory photography may be an effective
      qualitative research method for learning about the perspectives and experiences
      of children with disabilities on a wide array of topics. There are many specific
      modifications that researchers can use to support the inclusion of children with
      disabilities in participatory photography research. The findings of studies that
      use participatory photography methodology may provide rehabilitation
      professionals with important insights into the lives of children with
      disabilities.

PMID- 29587539
TI  - Green approach to the extraction of major capsaicinoids from habanero pepper
      using near-infrared, microwave, ultrasound and Soxhlet methods, a comparative
      study.
AB  - A simple method for the extraction of two major capsaicinoids from habanero
      peppers, using near-infrared irradiation, microwave irradiation or ultrasound as
      the energy source and ethanol as the solvent, was compared with Soxhlet
      extraction. The extraction processes were monitored by gas chromatography/mass
      spectrometry. The new processes offer better overall yields and a higher ratio of
      capsaicin to dihydrocapsaicin than Soxhlet extraction. The physical effect of the
      different energy sources on the peppers was determined using scanning electron
      microscopy. Extraction of capsaicin and dihydrocapsaicin using near-infrared
      irradiation, which has not been previously reported, was shown to be a simple and
      efficient alternative extraction procedure.

PMID- 29587540
TI  - Risk of recurrent shoulder dystocia: are we any closer to prediction?
AB  - OBJECTIVE: To determine the incidence and risk factors for recurrent shoulder
      dystocia in women. METHODS: We searched Medline, Pubmed, Embase, and CINAHL for
      relevant articles in English and French from 1980 to February 2018 that described
      risks of recurrent shoulder dystocia undergoing a trial of labour in subsequent
      pregnancies. A total of 684 articles were found, of which 13 were included as
      they met criteria. We extracted data on study characteristics, incidence of
      recurrent shoulder dystocia, degree of neonatal injury, and presence of known
      risk factors. RESULTS: There was a wide variation in the incidence of shoulder
      dystocia in subsequent pregnancies from 1-25%. The largest cohort reported a risk
      of 13.5%. The most important risk factor for recurrent shoulder dystocia is an
      increase in birthweight in the subsequent pregnancy compared to the index
      pregnancy (OR 7-12). Prolonged second stage, instrumental delivery, maternal
      diabetes, increased maternal BMI, and severe neonatal morbidity in the index
      pregnancy were also associated with an increased risk of recurrent shoulder
      dystocia. However, many of these risk factors were present in women who did not
      have a recurrent shoulder dystocia. In addition, women with recurrent shoulder
      dystocia rarely had identifiable risk factors, other than the history of previous
      shoulder dystocia. Sample sizes were low as most studies are single centre,
      retrospective cohorts with low rates of subsequent pregnancy and vaginal birth as
      many women may have elected to have a caesarean section in subsequent pregnancies
      or were lost to follow up. There was a high rate of reporting bias and
      heterogeneity, prohibiting formal meta-analyses. CONCLUSION: Recurrent shoulder
      dystocia is an unpredictable obstetric complication with potentially devastating
      consequences. Individual assessment and thorough counselling should be offered to
      women contemplating a subsequent planned vaginal birth with specific attention
      paid to those women where the estimated birthweight is >4000 g or greater than in
      the index pregnancy.

PMID- 29587541
TI  - Effect of Holder pasteurization on macronutrients and immunoglobulin profile of
      pooled donor human milk.
AB  - OBJECTIVE: The objective of this study was to study the effect of Holder
      pasteurization on macronutrients and immunoglobulin profile of pooled donor human
      milk. METHODS: This descriptive study was conducted in a Human Milk Bank of a
      tertiary care teaching institute in south India. Thirty random paired pooled
      donor human milk samples (before and after pasteurization) were analyzed for
      macronutrients (protein, fat, carbohydrates) using infrared spectroscopy.
      Similarly, immunoglobulin profile (IgA and IgG) before and after pasteurization
      was quantified using ELISA. RESULTS: The mean values of protein, fat, and
      carbohydrates in pooled donor milk pre-pasteurization were 1.6, 3.6, and 6.1 g/dl
      compared with post-pasteurization values 1.4, 2.7, and 5.9 g/dl, respectively.
      Pasteurization reduced protein, fat, and energy content of pooled donor milk by
      12.5%, 25%, and 16%, respectively. However, carbohydrates were not significantly
      reduced. Pasteurization decreased IgA by 30% and IgG by 60%. CONCLUSION: Holder
      pasteurization of pooled donor human milk decreases protein, fat, and energy
      content and also reduces the levels of IgA and IgG.

PMID- 29587542
TI  - Effects of maternal folic acid supplementation on airway remodeling and allergic
      airway disease development.
AB  - OBJECTIVE: Maternal folic acid supplementation has been recommended prior to and
      during the first trimester of pregnancy to reduce the risk of infant neural tube
      defects. However, an uncertain relationship between folic acid supplementation
      during pregnancy and development of childhood asthma exists. Recent data show a
      methyl donor-rich diet could increase the risk of developing allergic airway
      disease through DNA methylation and aberrant gene transcription. This study
      evaluated the effect of folic acid supplementation during pregnancy on airway
      remodeling and allergic airway disease vulnerability in a mouse asthma model.
      METHODS: BALB/c mice were divided into four groups according to gestational folic
      acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole
      pregnancy folic acid supplementation + OVA-exposed group), Group 2 (first
      gestational week folic acid supplementation + OVA-exposed group), Group 3 (no
      folic acid supplementation + OVA-exposed group), and Group 4 (control group).
      Offspring were sacrificed on day 45 for immunohistological and ultrastructural
      tests. RESULTS: In OVA challenged groups, folic acid supplementation led to a
      thicker epithelial and subepithelial smooth muscle layer than in the
      unsupplemented group. Moreover, folic acid supplementation during whole pregnancy
      (Group 1) was associated with a thicker epithelial and subepithelial smooth
      muscle layer than folic acid supplementation during the first week of pregnancy
      (Group 2), suggesting a duration-response relationship. Electron microscopic
      imaging revealed that structural changes including the loss of epithelial
      integrity, thickening of basement membrane, and subepithelial fibrosis were more
      prominent in the folic acid supplementation groups. CONCLUSIONS: This study
      suggested that maternal folic acid supplementation during pregnancy affects
      airway remodeling and increases the allergic responses induced by ovalbumin
      challenge in offspring. In addition, the effect size increased as the duration
      and cumulative dose increased.

PMID- 29587543
TI  - Iron overdose epidemiology, clinical features and iron concentration-effect
      relationships: the UK experience 2008-2017.
AB  - BACKGROUND: Iron poisoning is potentially serious, but mortality has fallen
      worldwide since implementation of pack size and packaging restrictions, and
      changes in iron use during pregnancy. The management of individual cases of
      overdose remains problematic due to uncertainty about indications for antidote.
      We examine the epidemiology of iron overdose in hospital cases referred to the UK
      National Poisons Information Service (NPIS) and evaluate the toxicokinetics of
      iron in patients ingesting only iron preparations. METHODS: Anonymized hospital
      referral patient data from the NPIS database were collated for the period 1
      January 2008 to 31 July 2017. Information was extracted, where recorded, on type
      of ingestion [iron alone (single), or combined with other agents (mixed)],
      reported dose, iron salt, timed iron concentrations and symptoms. In single-agent
      ingestions, the relationships between reported elemental iron dose, early
      concentrations (4-6 h), and symptoms were evaluated in teenagers and adults (>=13
      years) and children (<=12 years) using standard statistical techniques
      (correlation and unpaired nonparametric comparisons). In those patients with
      sufficient sample points (three or more), a simple kinetic analysis was
      conducted. RESULTS: Of 2708 patients with iron overdoses referred by UK hospitals
      for advice during the 9.7 years study period, 1839 were single-agent ingestions.
      There were two peaks in age incidence in single-agent exposures; 539/1839 (28.4%)
      were <6 years (54.1% males) while 675/1839 (36.7%) were between 13 and 20 years
      (91% females), the latter a substantial excess over the proportion in the
      totality of hospital referrals to the NPIS in the same period (13-20 years:
      23,776/144,268 16.5%; 67.5% female) (p < .0001 overall and for female %). In 475
      teenagers and adults and 86 children, with at least one-timed iron concentration
      available, there was no correlation between stated dose and iron concentration
      measured 4-6 h post-ingestion. Observed peak iron concentrations were not related
      to reported symptoms in adults. Initial iron concentrations were significantly
      higher in 30 patients (25 adults, 5 children) who received desferrioxamine (DFO)
      compared to those that did not [no DFO: mean 63.8 MUmol/L (95% CI 62.1-65.6),
      median 64; DFO: mean 78.5 MUmol/L (95% CI 69.2-87.7), median 78.1; Mann-Whitney p
      < .0018). No significant differences in symptoms were observed pre-treatment
      between DFO-treated and untreated groups. No patients died in this cohort.
      CONCLUSION: Single-agent iron exposures reported from UK hospitals were most
      common in children <5 years and young people aged 13-20 years. Poisoning with
      organ failure was not identified and there were no fatalities. No correlations
      were observed between reported iron doses and early concentrations, or between
      iron concentrations and symptoms in this cohort of mild-to-moderate poisoning.

PMID- 29587544
TI  - Ferula pseudalliacea induces apoptosis in human colorectal cancer HCT-116 cells
      via mitochondria-dependent pathway.
AB  - Ferula species have diverse biological functions. This study set out to
      investigate the anti-proliferative effects of methanolic extract of F.
      pseudalliacea against human colon cancer HCT-116 cell line. Cytotoxic effects of
      F. pseudalliacea on HCT-116 cells was estimated by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium (MTT) assay. Real-time polymerase chain reaction (PCR)
      and Western blot were employed to analyze BAX and Bcl2 expression. Cell cycle
      analysis and apoptosis were conducted using flowcytometry and Annexin V/
      propidium iodide (PI) staining. Rhodamine 123 staining and enzyme-linked
      immunosorbent assay (ELISA) assay were employed to quantify the mitochondria
      membrane potential (MMP) and caspase 3 activity, respectively. F. pseudalliacea
      markedly decreased HCT-116 cells viability. The gene and protein expression of
      BAX were increased, whereas Bcl-2 was decreased in F. pseudalliacea treated
      cells. F. pseudalliacea induced apoptosis via promotion of cell cycle arrest,
      caspase 3 activation, and destruction of MMP. These results demonstrate that F.
      pseudalliacea extract is able to induce apoptosis in HCT-116 cells mainly by
      activation of the mitochondrial pathway.

PMID- 29587546
TI  - Uncovering the regional localization of inhaled salmeterol retention in the lung.
AB  - Treatment of respiratory disease with a drug delivered via inhalation is
      generally held as being beneficial as it provides direct access to the lung
      target site with a minimum systemic exposure. There is however only limited
      information of the regional localization of drug retention following inhalation.
      The aim of this study was to investigate the regional and histological
      localization of salmeterol retention in the lungs after inhalation and to compare
      it to systemic administration. Lung distribution of salmeterol delivered to rats
      via nebulization or intravenous (IV) injection was analyzed with high-resolution
      mass spectrometry imaging (MSI). Salmeterol was widely distributed in the entire
      section at 5 min after inhalation, by 15 min it was preferentially retained in
      bronchial tissue. Via a novel dual-isotope study, where salmeterol was delivered
      via inhalation and d3-salmeterol via IV to the same rat, could the effective gain
      in drug concentration associated with inhaled delivery relative to IV, expressed
      as a site-specific lung targeting factor, was 5-, 31-, and 45-fold for the
      alveolar region, bronchial sub-epithelium and epithelium, respectively. We
      anticipate that this MSI-based framework for quantifying regional and
      histological lung targeting by inhalation will accelerate discovery and
      development of local and more precise treatments of respiratory disease.

PMID- 29587547
TI  - Silver nanoparticles improve structural stability and biocompatibility of
      decellularized porcine liver.
AB  - No ideal cross-linking agent has been identified for decellularized livers (DLs)
      yet. In this study, we evaluated structural improvements and biocompatibility of
      porcine DLs after cross-linking with silver nanoparticles (AgNPs). Porcine liver
      slices were decellularized and then loaded with AgNPs (100 nm) after optimization
      of the highest non-toxic concentration (5 ug/mL) using Human hepatocellular
      carcinoma (HepG2) and EAhy926 human endothelial cell lines. The cross-linking
      effect of AgNPs was evaluated and compared to that of glutaraldehyde and ethyl
      carbodiimide hydrochloride and N-hydroxysuccinimide. The results indicated that
      AgNPs improved the ultra-structure of DLs' collagen fibres with good porosity and
      increased DLs' resistance against in vitro degradation with good
      cytocompatibility. AgNPs decreased the host inflammatory reaction against
      implanted porcine DL slices in vivo and increased the polarization of M2
      macrophages. Thus, structural and functional improvements of Porcine DLs could be
      achieved using AgNPs.

PMID- 29587548
TI  - In reply to 'early tracheostomy in traumatic brain injury- conundrum
      continues...'.

PMID- 29587545
TI  - Puerarin-loaded PEG-PE micelles with enhanced anti-apoptotic effect and better
      pharmacokinetic profile.
AB  - Puerarin (PUE) is the most abundant isoflavonoid in kudzu root. It is widely used
      as a therapeutic agent for the treatment of cardiovascular diseases. However, the
      short elimination half-life, poor-bioavailability, and acute intravascular
      hemolysis of PUE are the main obstacles to its widespread clinical applications.
      Whereas PEG-PE micelles possess the ability to release medicine slowly, enhance
      the cellular uptake of drugs and improve their biocompatibility. Therefore, it
      was aim to fabricate puerarin-loaded PEG-PE (PUE@PEG-PE) micelles to improve the
      pharmaceutical properties of drugs. It can be observed from the TEM images that
      PUE@PEG-PE micelles appeared obvious core-shell structure and remained well
      dispersed without aggregation and adhesion. PUE was successfully embedded in the
      core of PEG-PE micelles, which was confirmed by FT-IR and 1H NMR spectra. In
      vitro studies showed that PUE@PEG-PE micelles exhibited a sustained release
      behavior in pH 7.4 PBS buffer and decreased hemolysis rate of PUE. Compared with
      PUE, PUE@PEG-PE micelles showed a 3.2-fold increase in the half-life of PUE and a
      1.58-fold increase in bioavailability. In addition, the PUE@PEG-PE micelles
      exerted enhanced protective effect against isoprenaline-induced H9c2 cells
      apoptosis compared with PUE, as evident by decreased percentage of Hoechst
      positive cells, Caspase 3 activity, Bax expression, and increased Bcl-2
      expression. Notably, the PEG-PE micelles exhibited favorable cellular uptake
      efficiency on H9c2 cells, and this may account for their enhanced anti-apoptotic
      effect of the incorporated drug. Altogether, the PUE@PEG-PE micelles were not
      only able to control the drug release but also offered promise to enhance the
      pharmacokinetic and pharmacodynamic potential of PUE.

PMID- 29587549
TI  - The importance of the rehabilitation program following an internal hemipelvectomy
      and reconstruction with limb salvage - gait analysis and outcomes: a case study.
AB  - BACKGROUND: Chondrosarcomas account for approximately 20% of bone sarcomas, with
      the most common site being the lower limb. Hemipelvectomies that involve
      hindquarter amputation have previously been the treatment of choice for pelvic
      tumors. However, with advances in chemotherapy, radiotherapy, imaging and
      surgical techniques more patients are now being treated with limb salvage
      surgery. The rehabilitation outcomes following an internal hemipelvectomy have
      not been well identified and there is currently little, if any, gait analysis
      data on rehabilitation following hemipelvectomy in limb salvage patients. CASE
      DESCRIPTION: A 53-year-old male underwent an internal hemipelvectomy with limb
      salvage followed by a 2-year rehabilitation program. The aim of this case study
      is to describe temporal and spatial parameters, metabolic energy expenditure and
      joint kinematics of a patient with an internal hemipelvectomy who underwent a
      wide excision of a chondrosarcoma followed by intensive rehabilitation. OUTCOMES:
      Walking speed (1.6 m/s), stride length (1.7 m), stride width (0.13 m) and good
      symmetry in step length (right 0.85 m and left data 0.80 m) and stance time
      (right 62% and left 59%) indicate a walking pattern similar to the asymptomatic
      able bodied. Oxygen consumption was 16.6 ml/kg/min and oxygen cost 0.17 ml/kg/m.
      DISCUSSION: Following the intensive 2-year rehabilitation program this patient's
      gait pattern was similar to a control group with no statistically significant
      difference in the movement of the left and right knee and ankle joints. Some
      differences were identified against the control group in respect of the movement
      of the pelvis and hips, but this is partly to be expected. This case study
      highlights the functional outcomes that can be achieved following limb salvage
      surgery with intensive rehabilitation and a high level of motivation from the
      individual. Implications for rehabilitation Advancements in chemotherapy, imaging
      and surgical techniques have allowed more patients to be treated with internal
      hemipelvectomy. The rehabilitation outcomes following an internal hemipelvectomy
      have not been well identified and there is little gait analysis data. This case
      study highlights the functional outcomes that can be achieved following limb
      salvage surgery with intensive rehabilitation and motivation from the individual.
      Rehabilitation following internal hemipelvectomy should include goal setting,
      lymphoedema management, physiotherapy and an exercise program.

PMID- 29587550
TI  - Platelet glycoprotein receptors gene polymorphisms are associated with increased
      risk of late spontaneous abortions.

PMID- 29587551
TI  - Predictors of hearing loss self-management in older adults.
AB  - PURPOSE: To determine the factor structure of a clinical tool for the assessment
      of hearing loss self-management, and to identify predictors of the total score on
      the assessment and the extracted factor scores. MATERIALS AND METHODS: Hearing
      loss self-management assessments were conducted with 62 older adults. The factor
      structure of the assessment was determined by exploratory factor analysis.
      Multiple linear regression analyses identified significant contributors to the
      total score and to each of the extracted factors. RESULTS: Three factors were
      identified, each representing a distinct domain of hearing loss self-management:
      Actions, Psychosocial Behaviours, and Knowledge. The most common significant
      predictor was hearing health care experience, which predicted self-management
      overall and in the Actions and Knowledge domains. Health literacy predicted
      hearing loss self-management overall and in the Psychosocial Behaviours domain.
      Actions were additionally predicted by hearing aid self-efficacy and gender,
      Psychosocial Behaviours by health locus of control, and Knowledge by age.
      CONCLUSIONS: The results of the factor analysis suggested that hearing loss self
      management is a multidimensional construct. Each domain of hearing loss self
      management was influenced by different contextual factors. Subsequent
      interventions to improve hearing loss self-management should therefore be domain
      specific and tailored to relevant contextual factors. Implications for
      rehabilitation Hearing loss is a chronic health condition that requires on-going
      self-management of its effects on everyday life. Hearing loss self-management is
      multidimensional and encompasses the domains of Actions, Psychosocial Behaviours,
      and Knowledge. Different contextual factors influence each hearing loss self
      management domain, including previous experience receiving hearing health care
      services, health literacy, hearing aid self-efficacy, health locus of control,
      age, and gender. Audiological rehabilitation programs should thus ensure that
      interventions to improve hearing loss self-management are domain- and context
      specific.

PMID- 29587552
TI  - Work disability negotiations: supervisors' view of work disability and
      collaboration with occupational health services.
AB  - PURPOSE: To introduce the Finnish practice of collaboration aiming to enhance
      work participation, to ask supervisors about its reasons and usefulness, to study
      supervisors' needs when they face work disability, and to compare the experiences
      of supervisors whose profiles differ. MATERIALS AND METHODS: An online
      questionnaire based on the Finnish practice of collaboration between supervisor
      and occupational health services (OHS) went to supervisors in six public and
      private organizations. A total of 254 supervisors responded, of whom, 133 (52%)
      had collaborated in work disability negotiations, representing a wide variety
      with differing professional profiles. RESULTS: In their role of managing work
      disability, supervisors appeared to benefit from three factors: an explicit
      company disability management (DM) policy, supervisors' training in DM, and
      collaboration with OHS. Reasons for work disability negotiations were long or
      repeated sick-leaves and reduced work performance. Expectations for occupational
      health consultations focused on finding vocational solutions and on obtaining
      information. Supervisors assessed the outcomes of collaboration as both
      vocational and medical. Supervisors with differing professional profiles
      prioritized slightly different aspects in collaboration. CONCLUSIONS:
      Collaboration with OHS is an important option for supervisors to enhance work
      modifications and the work participation of employees with work disability.
      Implications for Rehabilitation Work disability negotiation between supervisor,
      employee, and occupational health services (OHS) is an effective method to
      enhance work participation. Collaboration with occupational health can advance
      work modifications and also lead to medical procedures to improve work
      performance. Supervisor training, companies' explicit disability management
      policy, and collaboration with OHSs all advance employee's work participation.
      Collaboration with OHSs may serve as training for supervisors in their
      responsibility to support work participation.

PMID- 29587553
TI  - A fatality following difluoroethane exposure with blood and tissue
      concentrations.

PMID- 29587554
TI  - Irreversible profound symptomatic bradycardia requiring pacemaker after
      tizanidine/loxoprofen combination therapy: a case report.
AB  - A 37-year-old man suffered irreversible profound symptomatic bradycardia
      requiring a pacemaker 3 days after beginning tizanidine/loxoprofen combination
      therapy for neck pain. This combination therapy is prescribed frequently for
      joint pain; however, combining loxoprofen with tizanidine could increase the risk
      of symptomatic bradycardia that is both permanent and severe. Similar cases have
      not been reported. This case suggests that tizanidine should be used cautiously
      when combined with loxoprofen, and drug interaction screening should be
      performed.

PMID- 29587556
TI  - Editor's Note.

PMID- 29587555
TI  - Discovery and development of varenicline for smoking cessation.
AB  - INTRODUCTION: Tobacco use causes one premature death every six seconds. Current
      smoking cessation aids include nicotine replacement therapies, bupropion, and
      varenicline. Although more than 70% of smokers express a desire to quit, fewer
      than 3% remain abstinent for more than one year, highlighting a critical need for
      more efficacious smoking cessation treatments. Areas covered: The authors discuss
      the rationale, preclinical and clinical development of varenicline for smoking
      cessation. They cover the development of varenicline as a partial agonist at
      alpha4beta2 receptors, the primary neural substrate for nicotine reward. Then,
      they discuss evidence from preclinical studies indicating varenicline's efficacy
      in blocking nicotine reward, followed by clinical trials demonstrating safety and
      efficacy in sustaining abstinence in smokers. Finally, they cover post-market
      surveillance, including caution in heavy machine operators, putative
      cardiovascular risk, and the repealed warning for adverse neuropsychiatric
      events. Expert opinion: Varenicline development was based on strong theoretical
      rationale and preclinical evidence. Clinical studies indicate that varenicline is
      safe and more effective in sustaining abstinence than placebo, bupropion or
      nicotine replacement therapies. However, given that continuous abstinence rates
      across studies remain low (18 ~ 30% with varenicline; 4 ~ 10% with placebo),
      novel and more effective medications targeting other nicotinic or glutamate
      receptors for smoking cessation are required.

PMID- 29587558
TI  - Corrigendum.

PMID- 29587557
TI  - Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic
      Kidney Disease.
AB  - Polycystic kidney disease is characterized by the progressive development of
      kidney cysts and declining renal function with frequent development of cysts in
      other organs including the liver. The polycystic kidney (PCK) rat is a rodent
      model of polycystic liver disease that has been used to study hepatorenal disease
      progression and evaluate pharmacotherapeutic interventions. Biomarkers that
      describe the cyst progression, liver impairment, and/or hepatic cyst burden could
      provide clinical utility for this disease. In the present study, hepatic cyst
      volume was measured by magnetic resonance imaging in PCK rats at 12, 16, and 20
      weeks. After 20 weeks, Sprague Dawley (n = 4) and PCK (n = 4) rats were
      sacrificed and 42 bile acids were analyzed in the liver, bile, serum, and urine
      by liquid chromatography coupled to tandem mass spectrometry. Bile acid profiling
      revealed significant increases in total bile acids (molar sum of all measured
      bile acids) in the liver (13-fold), serum (6-fold), and urine (3-fold) in PCK
      rats, including those speciated bile acids usually associated with
      hepatotoxicity. Total serum bile acids correlated with markers of liver
      impairment (liver weight, total liver bile acids, total hepatotoxic liver bile
      acids, and cyst volume [ r > 0.75; P < 0.05]). Based on these data, serum bile
      acids may be useful biomarkers of liver impairment in polycystic hepatorenal
      disease.

PMID- 29587560
TI  - Location and structure of fibrous sheath formed after placing a tunneled
      hemodialysis catheter in a large pig model.
AB  - BACKGROUND AND OBJECTIVES: We evaluated the location and structure of the fibrous
      sheath formed after the placement of tunneled, cuffed hemodialysis catheters in
      large animals, 70 kg pigs. We focused on describing the location of the fibrous
      sheath in relation to the catheter. Its location explains the fibrous sheath's
      ability to cause catheter dysfunction by covering the catheter exit ports located
      at the catheter's tip. DESIGN: We used three animals. Each animal had a tunneled,
      cuffed, 15-French diameter hemodialysis catheter placed in the external jugular
      vein, with the tip at the junction of the superior vena cava and the right
      atrium. Two animals were sacrificed at 5 weeks and one animal at 17 weeks after
      catheter placement. The catheter and surrounding tissues were removed in one
      block. The fibrous sheath was dissected and longitudinally cut along the catheter
      to evaluate its extension in relation to the catheter. Relevant portions of the
      fibrous sheath were sent for pathology examination. RESULTS: The fibrous sheath
      covered the catheter in its entire length and circumference. It started at the
      entry site and continued without any interruption along the entire length of the
      catheter, including the tip. Its average thickness is 1 mm and has an inner
      cellular/inflammatory layer comprising lymphocytes, plasma cells, neutrophils,
      macrophages, multinucleated giant cells, and spindled cells and an outer layer
      comprising a mixture of collagen and fibroblasts. CONCLUSION: Our model showed
      that the fibrous sheath forms around all catheters and covers them in their
      entire length and circumference without any gaps.

PMID- 29587559
TI  - Involvement of pro-inflammation signal pathway in inhibitory effects of rapamycin
      on oxaliplatin-induced neuropathic pain.
AB  - Background Oxaliplatin is a third-generation chemotherapeutic agent that is
      commonly used to treat metastatic digestive tumors; however, one of the main
      limiting complications of oxaliplatin is painful peripheral neuropathy. The
      purpose of this study was to examine the underlying mechanisms by which mammalian
      target of rapamycin (mTOR) and its signal are responsible for oxaliplatin-evoked
      neuropathic pain. Methods Neuropathic pain was induced by intraperitoneal
      injection of oxaliplatin in rats. ELISA and Western blot analysis were used to
      examine the levels of pro-inflammatory cytokines (including interleukin (IL)
      1beta, IL-6, and tumor necrosis factor (TNF)-alpha) and the expression of mTOR
      signal pathway. Results Oxaliplatin increased mechanical and cold sensitivity as
      compared with control animals ( P < 0.05 vs. control rats). Oxaliplatin also
      amplified the expression of p-mTOR and mTOR-mediated phosphorylation of p70
      ribosomal S6 protein kinase 1 and 4E-binding protein 1 in the lumbar dorsal root
      ganglion. Blocking mTOR using rapamycin attenuated peripheral painful neuropathy
      observed in oxaliplatin rats ( P < 0.05 vs. vehicle control). This inhibitory
      effect was accompanied with decreases of IL-1beta, IL-6, and TNF-alpha. In
      addition, inhibition of phosphatidylinositide 3-kinase (p-PI3K) attenuated the
      expression of p-mTOR and the levels of pro-inflammatory cytokines in oxaliplatin
      rats, and this further attenuated mechanical and cold hypersensitivity.
      Conclusions The data revealed specific signaling pathways leading to oxaliplatin
      induced peripheral neuropathic pain, including the activation of PI3K-mTOR and
      pro-inflammatory cytokine signal. Inhibition of these pathways alleviates
      neuropathic pain. Targeting one or more of these molecular mediators may present
      new opportunities for treatment and management of neuropathic pain observed
      during chemotherapeutic application of oxaliplatin.

PMID- 29587561
TI  - Infant follow-up postdelivery from a hepatitis C viral load positive mother.
AB  - OBJECTIVE: The primary current recommendation for infant follow-up postdelivery
      from a hepatitis C virus (HCV) viral load positive mother is to evaluate for the
      presence of antibody at or after 18 months of age. Our study objective was to
      analyze compliance with this recommendation for postdelivery infant HCV screening
      at our institution among a cohort of infants delivered from HCV viral load
      positive mothers. METHODS: Starting 1 January, 2015, a prospective database was
      developed for all pregnancies that involved mothers with a positive HCV viral
      load during pregnancy. This short report describes the infant follow-up for
      deliveries through 30 June, 2016. At hospital discharge, all neonates were given
      follow-up pediatric appointments and mothers were supplied the date and time of
      the appointment along with the pediatric group name, office directions, and phone
      number. Statistics involved simple percentages with Poisson binomial 95%
      confidence intervals. RESULTS: A total of 127 newborns were delivered of HCV
      viral load positive mothers during the study period and 55 (43%, 95% CI 35-52%)
      attended their pediatric appointments and were still in follow-up. Regarding the
      72 cases (57%, 95% CI 48-65%) not in follow-up, 24 (19%, 95% CI 13-27%) never
      presented to care and 48 (38%, 95% CI 29-47%) came to one or two visits shortly
      after delivery but were absent for further follow-up. CONCLUSIONS: These data
      demonstrate that follow-up at 18 months postdelivery from an HCV viral load
      positive mother occurs in less than half of the cases and alternative screening
      strategies should be evaluated.

PMID- 29587562
TI  - Correlation between umbilical arterial pH values and fetal vertebral artery
      Doppler waveforms at the beginning of the second stage of labor: a pilot
      prospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between
      umbilical arterial pH and fetal vertebral artery Doppler velocimetry waveforms
      measured at the beginning of the second stage of labor in physiological term
      pregnancies. METHODS: This was a prospective cohort study of 250 pregnancies. The
      resistance index, pulsatility index, and peak systolic velocity were measured.
      The relationship between the fetal Doppler and the umbilical arterial pH was
      evaluated. A simple linear regression and a general linear model were used to
      explore possible correlations of Doppler parameters with fetal and neonatal
      outcome adjusted for confundents. RESULTS: Umbilical arterial pH values were
      directly associated with vertebral artery pulsatility index. Fetuses with lower
      pulsatility index values were at increased risk of a subsequent diagnosis of
      pathological fetal heart rate tracing patterns (presence of decelerations or
      reduced variability according to FIGO criteria during the second stage of labor).
      We estimated a decrease in pulsatility index of 10% in those fetuses destined to
      show a pathological fetal heart rate tracing. CONCLUSION: Vertebral artery
      Doppler waveforms correlates with umbilical pH in normal pregnancies and is also
      a function of fetal heart rate patterns. If this proportional association would
      be demonstrated also for abnormal pH values, vertebral artery pulsatility index
      might be useful to evaluate fetal wellbeing in those cases of suspected
      hypoxia/academia.

PMID- 29587563
TI  - Predictive role of endothelin in left ventricular remodeling of chronic kidney
      disease.
AB  - BACKGROUND: In chronic kidney disease (CKD), endothelin-1 (ET-1) always increases
      and there are changes in cardiac ultrasonography. In the present study, we aimed
      at investigating the role of serum ET-1 in predicting cardiac complications in
      patients with CKD. METHODS: The level of serum ET-1 was measured by enzyme-linked
      immunosorbent assay (ELISA) and cardiac ultrasonography was performed in enrolled
      patients. Indexes of heart failure, such as left ventricular mass index,
      interventricular septum thickness and left ventricular end diastolic diameter,
      were measured in patients with CKD. RESULTS: In the present study, we found that
      the level of serum ET-1 was significantly correlated with left ventricular mass
      index, interventricular septum thickness and left ventricular end diastolic
      diameter (p < .001) in non-dialysis patients with CKD. CONCLUSIONS: The results
      of the present study indicated that the level of serum ET-1 is closely related to
      the cardiac complications of CKD and is a useful predictor of cardiac
      complication.

PMID- 29587564
TI  - Mirtazapine attenuates nicotine-seeking behavior in rats.
AB  - BACKGROUND: Nicotine is the major psychoactive component of tobacco. A number of
      pharmacological therapies have been evaluated, with poor results. Given the lack
      of success of these therapies, several authors have proposed alternative
      therapeutic strategies. One of these is the use of antidepressant drugs that may
      have a specific effect on the neural pathways or receptors underlying nicotine
      addiction. Mirtazapine is an antagonist of alpha2 NE receptors (noradrenergic
      receptor), 5-HT2A/C and 5-HT3 receptors and has demonstrated efficacy in reducing
      behavioral effects induced by drugs of abuse in human and animal models. AIMS: In
      this study, we evaluated the effect of chronic dosing of mirtazapine during
      extinction on the re-acquisition of nicotine-seeking in rodents. METHODS: We used
      the nicotine self-administration paradigm to assess the effects of mirtazapine on
      rats trained to self-administer nicotine under a pharmacological fixed-ratio
      schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction.
      RESULTS: In this work, we found that mirtazapine attenuates the re-acquisition of
      nicotine-seeking responses. CONCLUSIONS: These results support the use of
      mirtazapine in clinical controlled trials as a useful therapy that prolongs and
      increases rates of preventing relapse into nicotine intake in humans.

PMID- 29587565
TI  - Fronto-limbic disconnection in patients with multiple sclerosis and depression.
AB  - BACKGROUND: The biological mechanism of depression in multiple sclerosis (MS) is
      not well understood. Based on work in major depressive disorder, fronto-limbic
      disconnection might be important. OBJECTIVE: To investigate structural and
      functional fronto-limbic changes in depressed MS (DMS) and non-depressed MS
      (nDMS) patients. METHODS: In this retrospective study, 22 moderate-to-severe DMS
      patients (disease duration 8.2 +/- 7.7 years), 21 nDMS patients (disease duration
      15.3 +/- 8.3 years), and 12 healthy controls underwent neuropsychological testing
      and magnetic resonance imaging (MRI; 1.5 T). Brain volumes (white matter (WM),
      gray matter, amygdala, hippocampus, thalamus), lesion load, fractional anisotropy
      (FA) of fronto-limbic tracts, and resting-state functional connectivity (FC)
      between limbic and frontal areas were measured and compared between groups.
      Regression analysis was performed to relate MRI measures to the severity of
      depression. RESULTS: Compared to nDMS patients, DMS patients (shorter disease
      duration) had lower WM volume ( p < 0.01), decreased FA of the uncinate
      fasciculus ( p < 0.05), and lower FC between the amygdala and frontal regions ( p
      < 0.05). Disease duration, FA of the uncinate fasciculus, and FC of the amygdala
      could explain 48% of variance in the severity of depression. No differences in
      cognition were found. CONCLUSION: DMS patients showed more pronounced (MS)
      damage, that is, structural and functional changes in temporo-frontal regions,
      compared to nDMS patients, suggestive of fronto-limbic disconnection.

PMID- 29587567
TI  - Exploring moral problems and moral competences in midwifery: A qualitative study.
AB  - BACKGROUND: Most undergraduate midwifery curricula comprise ethics courses to
      strengthen the moral competences of future midwives. By contrast, surprisingly
      little is known about the specific moral competences considered to be relevant
      for midwifery practice. Describing these competences not only depends on generic
      assumptions about the moral nature of midwifery practice but also reflects which
      issues practitioners themselves classify as moral. OBJECTIVE: The goal of this
      study was to gain insight into the ethical issues midwives encounter in their
      daily work, the key competences and resources they consider indispensable to
      understand and deal with them, and to assess phenomena linked to moral distress.
      METHODS: We conducted individual semi-structured interviews with eight midwives
      and two other health professionals, varying in terms of years of experience and
      work setting. Interview transcripts were analyzed in an interdisciplinary
      research group, following thematic analysis. Ethical considerations: This study
      was not subject to approval according to the Swiss Law on Research with Humans.
      Participants were informed about the study goals and gave written informed
      consent prior to participation. RESULTS: External constraints limiting the
      midwife's and the patient's autonomy and resulting interpersonal conflicts were
      found to be the most relevant ethical issues encountered in clinical practice and
      were most often associated with moral distress. These conflicts often arise in
      the context of medical interventions midwives consider as not appropriate and
      situations in which less experienced midwives in particular observe a lack of
      both interprofessional communication and trust in their professional competence.
      Ethical issues related to late abortions or prenatal diagnostics and selective
      abortions were also frequently addressed, but many midwives involved had learned
      to cope with them. DISCUSSION: In the light of the ethical issues and factors
      contributing to phenomena of moral distress, an empirically grounded profile of
      moral competences is drafted. Curricular implications in the light of possible
      adaptations within undergraduate midwifery education are critically discussed.

PMID- 29587568
TI  - Metabolomics and Biomarker Discovery in Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of disability and
      mortality worldwide. The TBI pathogenesis can induce broad pathophysiological
      consequences and clinical outcomes attributed to the complexity of the brain.
      Thus, the diagnosis and prognosis are important issues for the management of
      mild, moderate, and severe forms of TBI. Metabolomics of readily accessible
      biofluids is a promising tool for establishing more useful and reliable
      biomarkers of TBI than using clinical findings alone. Metabolites are an integral
      part of all biochemical and pathophysiological pathways. Metabolomic processes
      respond to the internal and external stimuli resulting in an alteration of
      metabolite concentrations. Current high-throughput and highly sensitive
      analytical tools are capable of detecting and quantifying small concentrations of
      metabolites, allowing one to measure metabolite alterations after a pathological
      event when compared to a normal state or a different pathological process.
      Further, these metabolic biomarkers could be used for the assessment of injury
      severity, discovery of mechanisms of injury, and defining structural damage in
      the brain in TBI. Metabolic biomarkers can also be used for the prediction of
      outcome, monitoring treatment response, in the assessment of or prognosis of post
      injury recovery, and potentially in the use of neuroplasticity procedures.
      Metabolomics can also enhance our understanding of the pathophysiological
      mechanisms of TBI, both in primary and secondary injury. Thus, this review
      presents the promising application of metabolomics for the assessment of TBI as a
      stand-alone platform or in association with proteomics in the clinical setting.

PMID- 29587566
TI  - Comparison of the efficacy and safety of non-steroidal anti-inflammatory drugs
      for patients with primary dysmenorrhea: A network meta-analysis.
AB  - Objective Non-steroidal anti-inflammatory drugs are used as first-line treatment
      of primary dysmenorrhea, but there has been no optimal clinical choice among non
      steroidal anti-inflammatory drugs yet. The present study was to assess the
      relative benefits of different common non-steroidal anti-inflammatory drugs for
      primary dysmenorrhea patients with a network meta-analysis. Methods Randomized
      controlled trials were screened by our criteria and included in the network meta
      analysis. Pain relief was considered as primary outcomes and adverse effect was
      supplied as a safety outcome, while additional rescue, assessment score, and pain
      intensity difference were secondary outcomes. All the indexes were evaluated with
      odds ratio or standardized mean difference. Surface under cumulative ranking
      curve result was used to calculate the ranking of each treatment. Results
      Totally, 72 randomized controlled trials of 5723 patients and 13 drugs were
      included in our study after screening. As for pain relief, all drugs except
      nimesulide, rofecoxib, and waldecoxib were superior to aspirin (odds ratio with
      95% credible intervals, diclofenac: 0.28 (0.08, 0.86), flurbiprofen: 0.10 (0.03,
      0.29), ibuprofen: 0.32 (0.14, 0.73), indomethacin: 0.21 (0.07, 0.58), ketoprofen:
      0.25 (0.10, 0.64), mefenamic acid: 0.28 (0.09, 0.87), naproxen: 0.31 (0.15,
      0.64), piroxicam: 0.15 (0.03, 0.59), and tiaprofenic acid: 0.17 (0.04, 0.63)).
      Aspirin also required additional rescue when compared with the majority of other
      drugs (flurbiprofen: 3.46 (1.15, 11.25), ibuprofen: 6.30 (2.08, 20.09), mefenamic
      acid: 7.32 (1.51, 37.71), naproxen: 2.66 (1.17, 6.55), and tiaprofenic acid: 9.58
      (1.43, 94.63)). As for assessment of the whole treatment, ketoprofen, naproxen,
      rofecoxib, and ibuprofen got higher score significantly than placebo. In
      addition, ibuprofen performed better than placebo in pain intensity difference.
      Considering the safety, tiaprofenic acid and mefenamic acid were noticeable in
      low risk, and indomethacin revealed higher risk than any other drugs. According
      to the results of network analysis and surface under cumulative ranking curve,
      flurbiprofen was considered to be the best one among all the treatments in
      efficacy, and aspirin was worse than most of others. On the other hand,
      tiaprofenic acid and mefenamic acid were indicated as the safest drugs.
      Conclusion Considering the efficacy and safety, we recommended flurbiprofen and
      tiaprofenic acid as the optimal treatments for primary dysmenorrhea.

PMID- 29587569
TI  - Belonging and exclusion in the lives of young people with intellectual disability
      in small town communities.
AB  - In recent policies, it is assumed that communities welcome the inclusion of young
      people with intellectual disability. However, little is known about perspectives
      of young people themselves. This article reports on research that sought to
      address this gap. Young people with intellectual disability living in three
      Australian small town communities participated in pictorial mapping and photo
      rich methods to explore belonging and exclusion and links between these. Young
      people's feelings of comfort and safety with local spaces and people were
      important for their sense of belonging. Emplaced relationships with family and
      some friends were key to strong belonging, as were positive attachments to
      disability support workers and spaces. Social exclusion, either from particular
      places or more generally, was keenly felt. Young people's confidence, willingness
      to enter social spaces and relationships were magnified by ways that systems
      responded to their impairment, at worst fracturing their sense of feeling welcome
      and included.

PMID- 29587570
TI  - MUTYH and ORAI1 polymorphisms are associated with susceptibility to
      osteoarthritis in the Chinese Han population.
AB  - Background This study analyzed the associations between single nucleotide
      polymorphisms (SNPs) in the mutY homolog gene ( MUTYH) and the calcium release
      activated calcium channel gene ( ORAI1) with susceptibility to osteoarthritis in
      the Chinese Han population. Methods A total of 350 patients diagnosed with
      osteoarthritis from October 2013 to May 2016 were selected as the study group,
      together with 350 age- and gender-matched healthy controls. MUTYH SNP rs3219463
      and ORAI1 SNPs rs712853, rs12313273, rs6486795, rs12320939, and rs7135617 were
      analyzed by Sanger sequencing. Serum MUTYH levels were measured by enzyme-linked
      immunosorbent assay. The relationship between SNPs in MUTYH and ORAI1 and
      osteoarthritis susceptibility was analyzed and compared with the level of serum
      MUTYH in the osteoarthritis and control groups. Results MUTYH rs3219463 G allele
      carriers (GG or GA genotypes) and ORAI1 rs7135617 T allele carriers had a higher
      risk of osteoarthritis than patients with other genotypes. The level of serum
      MUTYH in the study group was significantly higher than in the control group
      (22.05 +/- 19.14 ng/mL vs. 14.15 +/- 13.54 ng/mL). Conclusions MUTYH and ORAI1
      SNPs are associated with osteoarthritis susceptibility in the Chinese Han
      population.

PMID- 29587572
TI  - Outcomes in Distressed Patients With Chronic Low Back Pain: Subgroup Analysis of
      a Clinical Trial.
AB  - Study Design Subgroup analysis of a controlled clinical trial. Background Current
      evidence suggests that people with chronic low back pain who are distressed may
      require different interventions than do those who are not distressed. Recently,
      the enhanced transtheoretical model intervention (ETMI) reported significant
      improvements in disability and pain and increased physical activity in patients
      with chronic low back pain compared to physical therapy as usual. Objectives To
      compare outcomes between ETMI and physical therapy interventions for participants
      with and without self-reported distress. Methods We tested the interaction
      between intervention (ETMI versus physical therapy) and distress status (using
      the Medical Outcomes Study 12-Item Short-Form Health Survey cut point), and
      performed between-group comparisons on 3 separate outcomes (disability, pain, and
      physical activity) at 3 and 12 months. Results In the ETMI group, 57 of 108
      participants were considered distressed, versus 62 of 106 participants in the
      physical therapy group. The interaction between intervention and distress at 12
      months was significant. Participants improved with both interventions, but the
      magnitude of change in distressed participants who received ETMI was larger than
      that in distressed participants who received physical therapy (mean +/- SD
      difference from baseline in disability of 6.1 +/- 6.1 in the ETMI group, compared
      with 3.4 +/- 6.7 in the physical therapy group). Conclusion The enhanced
      transtheoretical model intervention was significantly more effective than
      physical therapy in participants with distress. The trial was registered in
      ClinicalTrials.gov (NCT01631344). Level of Evidence Therapy, level 2b. J Orthop
      Sports Phys Ther 2018;48(6):491-495. Epub 27 Mar 2018.
      doi:10.2519/jospt.2018.7670.

PMID- 29587573
TI  - Physical Activity in Public Parks of High and Low Socioeconomic Status in
      Colombia Using Observational Methods.
AB  - BACKGROUND: Public parks are an important resource for the promotion of physical
      activity (PA). This is the first study in Colombia and the fourth in Latin
      America to describe the characteristics of park users and their levels of PA
      using objective measures. METHODS: A systematic observation assessed sex, age,
      and the level of PA of users of 10 parks in an intermediate-size city in
      Colombia, classified in low (5 parks) and high (5 parks) socioeconomic status
      (SES). A total of 10 daily observations were conducted, in 5 days of the week
      during 3 periods: morning, afternoon, and evening. RESULTS: In total, 16,671
      observations were completed, recording 46,047 users. A higher number of users per
      park, per day, were recorded in high SES (1195) versus low SES (647). More men
      were observed in low-SES than high-SES parks (70.1% vs 54.2%), as well as more
      children were observed in low-SES than high-SES parks (30.1% vs 15.9%). Older
      adults in high-SES parks were more frequent (9.5% vs 5.2%). Moderate to vigorous
      PA was higher in low-SES parks (71.7% vs 63.2%). CONCLUSIONS: Low-SES parks need
      more green spaces, walk/bike trails, and areas for PA. All parks need new
      programs to increase the number of users and their PA level, considering sex, age
      group, and period of the week.

PMID- 29587571
TI  - Clinical opioids differentially induce co-internalization of MU- and delta-opioid
      receptors.
AB  - Opioid receptors play an important role in mediating the spinal analgesia. The MU
      opioid receptor is the major target of opioid drugs widely used in clinics.
      However, the regulatory mechanisms of analgesic effect and tolerance for clinical
      MU-opioid receptor-targeting opioids remain to be fully investigated. Previous
      studies showed the interaction of delta-opioid receptor with MU-opioid receptor
      to form the MU-opioid receptor/delta-opioid receptor heteromers that could be
      processed in the degradation pathway after delta-opioid receptor agonist
      treatment. Here, we showed that clinical MU-opioid receptor-targeting opioids,
      morphine, fentanyl, and methadone, but not tramadol, caused MU-opioid receptor co
      internalization with delta-opioid receptors in both transfected human embryonic
      kidney 293 cells and primary sensory neurons. Prolonged treatment of morphine led
      to MU-opioid receptor co-degradation with delta-opioid receptors. Furthermore,
      fentanyl and methadone, but not tramadol, induced the drug tolerance similar to
      morphine. Thus, the clinical MU-opioid receptor-targeting opioids including
      morphine, fentanyl, and methadone induce MU-opioid receptor co-internalization
      with delta-opioid receptors, which may be involved in the analgesic tolerance of
      these opioids.

PMID- 29587574
TI  - Clinical characteristics of infectious ulceration over tophi in patients with
      gout.
AB  - Objective The aim of this study was to investigate the clinical characteristics
      of infectious ulceration over tophi in patients with gout. Methods Participants
      were recruited from the First Affiliated Hospital of Wenzhou Medical University.
      The clinical characteristics of the patients and wound characteristics were
      recorded. Results Of the 38 enrolled patients, 18 were found to have infectious
      ulceration over tophi. Staphylococcus aureus was the most common pathogen and was
      identified in nine patients. Patients with infection were significantly older
      (69.6 vs. 60.1 years) and had a worse quality of life than those without
      infection. Patients with infection also had a significantly longer ulcer duration
      (125.6 vs. 54.2 days), larger ulcer size (2.47 vs. 1.99 cm2), a higher rate of
      tissue necrosis in the ulcer bed (55.6% vs. 20.0%), a lower rate of callus at the
      edge (27.8% vs. 70.0%), and a higher moisture level than did patients without
      infection. Additionally, patients with infection had significantly delayed wound
      healing (35.3 vs. 20.3 days) compared with patients without infection.
      Conclusions Older patients with a long ulcer duration and larger ulcer size are
      more susceptible to infection. Infection can lower patients' quality of life and
      delay wound healing.

PMID- 29587575
TI  - The power of nonverbal communication in medical education.

PMID- 29587576
TI  - Optical coherence tomography angiography detects retinal vascular alterations in
      different phases of multiple sclerosis.

PMID- 29587577
TI  - Effect of Carbapenem Selection on Drug Acquisition Costs and Carbapenem
      Resistance.

PMID- 29587578
TI  - Maternal sensitivity in mother-infant interactions in Rio de Janeiro - Brazil.
AB  - This article reports on a study of maternal sensitivity in 22 primiparous women
      and their infants from Rio de Janeiro, Brazil. Two semi-structured interviews
      were conducted, as well as videotaped naturalistic home observations of the
      dyads. A K-means cluster analysis was performed to examine patterns of risk in
      relation to maternal sensitivity. The results reveal that compared to the 15
      mothers with higher sensitivity scores, the 7 mothers with lower sensitivity
      scores were characterized by lower educational levels, lower income, lower age,
      living in a slum, unplanned and unwanted pregnancies, and later onset of prenatal
      care. Whether father was resident did not appear to distinguish between the lower
      and higher sensitivity groups. The article concludes that the patterns of social
      contextual risk for Brazilian mothers showing less sensitive caregiving to their
      infants provide a clear direction for future research in this cultural context.

PMID- 29587579
TI  - The forearm basilic vein looped transposition fistula as a tertiary option for
      upper limb vascular access.
AB  - INTRODUCTION:: The forearm basilic vein can serve as an option for haemodialysis
      access but may not be possible in cases where the wrist arteries are unsuitable.
      In this setting, the forearm basilic vein can be used in a looped transposition
      with a brachial artery anastomosis. AIMS:: The aims of this study were to assess
      the outcome of forearm basilic vein looped transposition as an option for
      vascular access. MATERIAL AND METHODS:: Data from January 2007 to December 2010
      were prospectively collected and analysed. Outcome measures were operative
      success, complications, maturation and primary and secondary patency following 5
      years of follow-up. RESULTS:: From a total of 583 patients receiving autologous
      vascular access for haemodialysis, 24 (4.1%) underwent a forearm basilic vein
      looped transposition. The median age was 60 years (range, 27-80 years), with a
      slight male predominance (13 male:11 female). Mean follow-up was 34 months (1-60
      months). Two patients died and other three were transplanted with subsequent
      fistula closure. All procedures were successful (100%); however, maturation
      failure occurred in one case (4.2%). No serious perioperative complications were
      observed. In two cases, we observed late false aneurysm formation requiring
      intervention. Primary patency at 1, 2, 3 and 5 years was the following: 77%, 62%,
      21% and 10%, whereas secondary patency was the following: 81%, 71%, 61% and 32%,
      respectively. CONCLUSION:: Autologous forearm basilic vein looped transposition
      is an effective surgical procedure for the creation of access for haemodialysis.
      This may be a useful option in patients with compromised peripheral arterial
      diameter or flow and should be considered in patients with a suitable forearm
      basilic vein.

PMID- 29587581
TI  - Comparisons of Multilevel Modeling and Structural Equation Modeling Approaches to
      Actor-Partner Interdependence Model.
AB  - There are basically two modeling approaches applicable to analyzing an actor
      partner interdependence model: the multilevel modeling (hierarchical linear
      model) and the structural equation modeling. This article explains how to use
      these two models in analyzing an actor-partner interdependence model and how
      these two approaches work differently. As an empirical example, marital conflict
      data were used to analyze an actor-partner interdependence model. The multilevel
      modeling and the structural equation modeling produced virtually identical
      estimates for a basic model. However, the structural equation modeling approach
      allowed more realistic assumptions on measurement errors and factor loadings,
      rendering better model fit indices.

PMID- 29587580
TI  - Comparing two measures of maternal sensitivity: goodness of fit with a South
      African cultural context.
AB  - Recent scholarly insights show that nonverbal and subtle forms of sensitive
      responsiveness are more applicable to describing and assessing non-Western parent
      infant interactions than the more extraverted Western varieties of
      responsiveness. This paper examines whether the original Ainsworth scale (that
      does not specify particular manifestations of sensitivity) reveals different
      patterns of results in 50 South African mothers when compared to the Maternal
      Behavior Q-sort mini that assesses a more specified array of behaviors that may
      vary in their goodness of fit regarding the cultural context. The analysis
      reveals that there are key differences in the way the two measures operationalize
      maternal sensitivity, as seen in the incongruence of sensitivity ratings. The two
      measures are also shown to relate differently to maternal education and
      reflective functioning in this sample. The paper concludes that the Ainsworth
      sensitivity scale is better suited for use in the context of Alexandra Township,
      Johannesburg.

PMID- 29587582
TI  - Spironolactone to increase natriuresis in congestive heart failure with
      cardiorenal syndrome.
AB  - BACKGROUND: Signs and symptoms of volume overload are the most frequent reason
      for hospital admission in acute heart failure (AHF). Diuretics are mainstay
      treatment, but their optimal type and dose regimen remain unclear, especially in
      patients with cardiorenal syndrome. METHODS: This prospective study aimed to
      include 80 AHF patients with volume overload and cardiorenal syndrome. Through a
      2 * 2 factorial design, patients were randomised towards (1) combinational
      treatment with acetazolamide and low-dose loop diuretics versus high-dose loop
      diuretics; and (2) open-label oral spironolactone 25 mg OD given upfront versus
      at discharge. Here reported are the results of the spironolactone treatment arm
      after complete follow-up of 34/80 patients (since the study was stopped because
      of slow recruitment). The primary study end-point was incident hypokalaemia (<3.5
      mmol/L) or hyperkalaemia (>5.5 mmol/L). RESULTS: Serum potassium derangements
      were numerically less frequent in the upfront versus discharge spironolactone
      group, yet this result was underpowered due to incomplete study recruitment
      (hyperkalaemia: 6% vs. 11%; hypokalaemia: 13% vs. 28%, respectively; p-value =
      .270). Natriuresis after 24 h was higher in the upfront vs. discharge
      spironolactone group (314 +/- 142 vs. 200 +/- 91 mmol/L, respectively; p-value =
      .010). Relative change in plasma NT-proBNP level after 72 h was similar among
      both groups (-16 +/- 29% vs. -5 +/- 45%, respectively; p value = .393), with no
      difference in all-cause mortality (p-value = .682) or the combination of all
      cause mortality and heart failure readmission (p-value = .799). DISCUSSION:
      Spironolactone use upfront in AHF patients at high risk for cardiorenal syndrome
      is safe and increases natriuresis.

PMID- 29587584
TI  - ?

PMID- 29587583
TI  - Systematic Review and Meta-Analysis of Unplanned Reoperations, Emergency
      Department Visits and Hospital Readmission After Thyroidectomy.
AB  - BACKGROUND: Unplanned reoperation, emergency department (ED) visits, and hospital
      readmission following thyroid operations usually arise due to complications and
      are a source of frustration for both surgeons and patients. With the aim of
      providing insight important for the development of patient quality care
      improvement initiatives, the primary objective of this review was to evaluate the
      available literature systematically in order to determine the contemporary rates
      of reoperation, readmission, and ED visits following thyroid operations. A
      secondary study objective was to determine if there were any practices that
      showed promise in reducing the occurrence of these undesirable postoperative
      events. METHODS: This systematic review was conducted in accordance with the
      Preferred Reporting of Items for Systematic Reviews and Meta-Analyses protocols.
      Twenty-two studies were included in the systematic review. Meta-analysis was
      performed to obtain the weighted-pooled summary estimates of rates of
      reoperations, ED visits, and unplanned hospital readmission. Jackknife
      sensitivity analyses were performed for each data set. Finally, in order to
      detect the risk of publication bias and the small-study effect, funnel plot
      analysis was performed. RESULTS: The pooled rate estimate for reoperation was
      very low (0.6% [confidence interval (CI) 0.3-1.1%]). This was subject to
      publication bias because smaller studies tended to report lower rates of
      reoperation. The pooled rate of ED visits was 8.1% [CI 6.5-9.8%], while the
      pooled rate of hospital readmission from 19 studies was 2.7% [CI 2.1-3.4%]. Neck
      hematoma was the most common reason for reoperation, while postoperative
      hypocalcemia was the most common reason for hospital readmission. CONCLUSIONS: ED
      visits and hospital readmission after thyroidectomy are common, and there are
      several practices that can reduce their occurrence. Routine postoperative calcium
      and vitamin D supplementation may reduce rates of postoperative hypocalcemia, and
      avoiding postoperative hypertension may decrease the risk of neck hematoma
      development and the need for reoperation. Older age, thyroid cancer, dependent
      functional status, higher ASA score, diabetes, chronic obstructive pulmonary
      disease, steroid use, hemodialysis, and recent weight loss increase the risk of
      hospital readmission after thyroid surgery. By further identifying risk factors
      for reoperation, ED visits, and readmission, this review may assist practitioners
      in optimizing perioperative care and therefore reducing patient morbidity and
      mortality after thyroid operations.

PMID- 29587585
TI  - ?

PMID- 29587586
TI  - ?

PMID- 29587587
TI  - ?

PMID- 29587588
TI  - ?

PMID- 29587589
TI  - ?

PMID- 29587590
TI  - ?

PMID- 29587591
TI  - ?

PMID- 29587592
TI  - ?

PMID- 29587593
TI  - [CME: Hypocalcemia].

PMID- 29587594
TI  - ?

PMID- 29587595
TI  - Health-related quality of life before and after hematopoietic stem cell
      transplant: evidence from a survey in Suzhou, China.
AB  - OBJECTIVES: The aim of our longitudinal study was to explore changes in HRQOL
      over a 6-month period and to identify factors associated with the HRQOL of HSCT
      recipients. METHOD: Our study comprised 191 HSCT patients; their data were
      collected before transplantation and at 30, 90, and 180 days posttransplantation.
      The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)
      questionnaire was used to assess HRQOL.We also evaluated the patients'
      demographic characteristics and clinical histories to determine the relative
      contributions of these factors to HRQOL outcomes. RESULTS: Before HSCT, the
      patients reported a mean overall HRQOL of 110.31 (SD, 14.99); this reached a
      minimum of 105.07 (SD, 18.85) at day 30 after HSCT and increased steadily over
      time to 106.71 (SD, 18.34) at day 90 and 108.16 (SD, 18.34) at day 180 after
      HSCT.Compared with baseline, overall HRQOL changed with the mean of -5.24 (SE
      1.55; P = .001), and -3.60 (SE 1.55; P = .022), respectively, at 30 days and 90
      days after HSCT. Overall HRQOL returned to near pretransplant levels at 180 days
      after HSCT (SE 1.47; P = .146).Generalized estimating equation (GEE) models
      showed that household income (beta = 6.590; P < .001), transplant-related
      complications (beta = -6.101; P < .001), and patient age (beta = 0.243, P = .045)
      were associated with HRQOL. CONCLUSION: The patients' overall HRQOL was severely
      impaired in the early stages of posttransplantation, and patients experienced the
      worst HRQOL at 30 days. They had improved significantly by 180 days
      posttransplantation. We also found that household income, transplant-related
      complications, and age were independent predictors of early HRQOL.We therefore
      concluded that the HRQOL of HSCT patients in the early stages posttransplantation
      deserved more attention.

PMID- 29587596
TI  - Observing sensitivity in slums in Yemen: the veiled challenge.
AB  - This study represents the first video observation of parenting practices
      conducted in Yemen, where filming women is a taboo, and women are generally fully
      veiled, showing only their eyes, in the presence of strangers. A total of 62
      mothers and children (aged 2-6 years) were filmed in their homes for 15 min
      during free interaction. The mothers' veils were not experienced as hampering the
      coding of sensitivity. Consistent with the socioeconomically deprived context,
      average sensitivity levels were low, but over 25% of mothers were rated as (very)
      sensitive. About half of the mothers elected to have their child do household
      chores, which in turn was related to lower levels of sensitivity. Observations
      revealed frequent looking at the camera. Almost half of the mothers verbally
      expressed insecurity about the videotaping, and a third expressed awareness of
      being filmed. Interestingly however, these behaviors were unrelated to Ainsworth
      ratings of maternal sensitivity.

PMID- 29587597
TI  - Ellagic acid as a potential antioxidant, alleviates methotrexate-induced
      hepatotoxicity in male rats.
AB  - BACKGROUND: Hepatotoxicity is one of the most life-threatening side-effects of
      Methotrexate therapy. Former studies highlighted the significance of oxidative
      stress in promoting Methotrexate-induced hepatotoxicity (MIH). Hence, the current
      study investigated the protective effect of Ellagic acid (EA), a poly-phenolic
      antioxidant, against MIH. METHODS: Twenty-eight male Wistar rats were grouped
      into four sets: group 1 (control), group 2 (injected intraperitoneally with 20
      mg/kg of Methotrexate on the 9th day), group 3 (treated orally with 10 mg/kg/day
      of EA for 10 days and injected with Methotrexate on the 9th day) and group 4
      (treated with EA for 10 days). Subsequently, biochemical and histopathological
      parameters were evaluated in serum samples and liver tissues. RESULTS:
      Methotrexate significantly increased activities of aminotransferases and ALP
      enzymes as well as levels of oxidative stress parameters in liver tissue.
      Likewise, Methotrexate decreased hepatic reduced glutathione level and activities
      of antioxidant enzymes. EA pre-treatment markedly attenuated the activities of
      aminotransferases and ALP, levels of oxidative stress parameters and augmented
      activities of antioxidant enzymes. Similarly, the remarkable protective effect of
      EA on liver has been confirmed by histological examination. CONCLUSION: In sum,
      the current study supports the hypothesis that EA may be used as a promising pre
      therapy to prevent the MIH.

PMID- 29587598
TI  - Economic Abuse as an Invisible Form of Domestic Violence: A Multicountry Review.
AB  - The predominant perception of intimate partner violence (IPV) as constituting
      physical violence can still dominate, particularly in research and media reports,
      despite research documenting multiple forms of IPV including sexual violence
      occurring between intimate partners and various forms of psychological and
      emotional abuse. One frequently hidden or "invisible" form of abuse perpetrated
      within intimate partner relationships is economic abuse, also referred to as
      financial abuse in much of the literature. While the links between gendered
      economic insecurity and economic abuse are emerging, there remains a lack of
      consistency about definitions within the United States and globally, as there is
      no agreed upon index with which to measure economic abuse. As such, the purpose
      of this article is to review and analyze the global literature focused on either
      economic or financial abuse to determine how it is defined and what measures are
      used to capture its prevalence and impact. The 46 peer-reviewed articles that met
      all inclusion criteria for analysis came from a range of countries across six
      continents. Our review found that there is growing clarity and consistency of
      terminologies being used in these articles and found some consistency in the use
      of validated measures. Since this research is in its "infancy," we need to have
      stronger collaborative efforts to use similar measures and terminology. Part of
      that collaborative effort is to consider how language and cultural differences
      may play a part in our understanding of economic abuse.

PMID- 29587599
TI  - Pathological and Clinical Pathological Changes Induced by Four-week, Repeated
      dose, Oral Administration of the Wood Preservative Chromated Copper Arsenate in
      Wistar Rats.
AB  - Chromated copper arsenate (CCA) is used as a wood preservative worldwide.
      Exposure to it may adversely affect human health. Some events have increased
      human exposure to CCA, including the Great East Japan Earthquake, which generated
      a large amount of lumber debris from CCA-treated woods. We elucidated the
      toxicity due to daily exposure to CCA over a 4-week period at doses of 0, 8, 40,
      and 80 mg/kg/day in Wistar Hannover rats. Chromium (Cr) and arsenic (As), but not
      copper, were detected in the plasma samples of rats treated with various doses of
      CCA. Males and females showed sedation, and males had poor body weight gain. The
      clinical pathologies observed in both sexes included hypochromic and microcytic
      anemia, hepatic and renal dysfunction, and changes in lipid and glucose levels.
      Histopathologically, males and females showed forestomach hyperkeratosis, mucosal
      epithelial hyperplasia in the small intestine, rectal goblet cell hypertrophy,
      and lipofuscin deposition in the proximal renal tubule. Females showed diffuse
      hepatocellular hypertrophy with increased 8-hydroxydeoxyguanosine levels. These
      results indicated that oral administration of CCA mainly affected hematopoietic,
      gastrointestinal, hepatic, and renal systems owing to the toxic effects of As
      and/or Cr. Major toxic effects were observed in both sexes receiving 40 and 80
      mg/kg/day.

PMID- 29587600
TI  - Anticancer redox activity of gallium nanoparticles accompanied with low dose of
      gamma radiation in female mice.
AB  - Guided treatments with nanoparticles and radiotherapy are a new approach in
      cancer therapy. This study evaluated the beneficial antitumor effects of gamma
      radiation together with gallium nanoparticles against solid Ehrlich carcinoma in
      female mice. Gallium nanoparticles were biologically synthesized using
      Lactobacillus helveticus cells. Transmission electron microscopy showed gallium
      nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles
      on MCF-7 revealed IC50 of 8.0 MUg. Gallium nanoparticles (0.1 mg/kg body weight)
      were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma
      cells inoculation. Whole-body gamma-radiation was carried out at a single dose of
      0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that
      solid Ehrlich carcinoma induced a significant increase in alanine
      aminotransferase activity and creatinine level in serum, calcium, and iron
      concentrations in liver tissue compared to normal control. Treatment of Ehrlich
      carcinoma-bearing mice with gallium nanoparticles and/or low dose of gamma
      radiation exposure significantly reduced tumor volume, decreased alanine
      aminotransferase and creatinine levels in serum, increased lipid peroxidation,
      and decreased glutathione content as well as calcium and iron concentrations in
      liver and tumor tissues with intense DNA fragmentation accompanied compared to
      untreated tumor cells. Moreover, mitochondria in the treated groups displayed a
      significant increase in Na+/K+-ATPase, complexes II and III with significant
      reduction in CYP450 gene expression, which may indicate a synergistic effect of
      gallium nanoparticles and/or low dose of gamma-radiation combination against
      Ehrlich carcinoma injury, and this results were well appreciated with the
      histopathological findings in the tumor tissue. We conclude that combined
      treatment of gallium nanoparticles and low dose of gamma-radiation resulted in
      suppressive induction of cytotoxic effects on cancer cells.

PMID- 29587601
TI  - Experimental evidence that preaxial polydactyly and forearm radial deficiencies
      may share a common developmental origin.
AB  - Preaxial polydactyly is a congenital hand anomaly predominantly of sporadic
      occurrence, which is frequently associated with abnormalities of the Sonic
      hedgehog signalling pathway. In experimentally induced preaxial polydactyly,
      radial aplasia is also frequently observed. To determine if there is a
      correlation between preaxial polydactyly and radial aplasia, we induced ectopic
      Sonic hedgehog signalling during chicken limb development with application of a
      smoothened-agonist (SAG) or retinoic acid. Application of SAG caused
      malformations in 71% limbs including preaxial polydactyly (62%) and forearm
      abnormalities (43%). Retinoic acid application induced malformations in 56% of
      limb including preaxial polydactyly (45%) and forearm abnormalities (50%). Radial
      dysplasia and ulnar dimelia were observed in both experimental conditions. We
      demonstrate that ectopic Sonic hedgehog signalling may cause both preaxial
      polydactyly and predictable forearm anomalies and that these conditions could
      potentially be classified as one embryological group. We propose a unifying model
      based on known models of ectopic Sonic hedgehog signalling.

PMID- 29587602
TI  - Kingella kingae hand and wrist tenosynovitis in young children.

PMID- 29587603
TI  - Fractures at the junction of diaphysis and metaphysis of the proximal phalanges
      in adults.
AB  - : We describe the treatment of 101 patients with 113 fractures of the proximal
      phalanx at the junction of the diaphysis with the proximal metaphysis. Fractures
      were stabilized using a single extra-articular percutaneous Kirschner wire passed
      lateral to the metacarpal head into the base of the phalanx base and across the
      fracture to engage the lateral cortex. Patients were treated semi-electively on a
      day surgery unit. The metacarpophalangeal joint was splinted in flexion with
      mobilization of the proximal inter-phalangeal joints, until the wire was removed
      at 24 days and the hand then freely mobilized. The mean total active movement was
      230 degrees  and no patients experienced problems with significant pain. There
      were two pin site infections. There were no cases of angular or rotational
      malunion. These injuries can be successfully and safely treated using this simple
      technique, negating the need for close monitoring for angular displacement of the
      fracture, which is frequently seen with non-surgical management. LEVEL OF
      EVIDENCE: IV.

PMID- 29587604
TI  - Effect of immobilization of the distal interphalangeal joint of fingers on grip
      strength.
AB  - Arthrodesis of the distal interphalangeal joint of the finger is an effective
      salvage treatment for end-stage arthropathy of the joint. This study aimed to
      evaluate the effect of simulated fusion of individual distal interphalangeal
      joints on the overall grip strength of the hand. Custom moulded thermoplastic
      splints were used to simulate fusion by immobilizing the index, middle, ring and
      little fingers' distal interphalangeal joints in turn in both hands of 56 healthy
      participants. Testing was performed with no immobilization and after
      immobilization of each of the individual digits. Grip strengths reduced
      significantly following immobilization of the distal interphalangeal joint. The
      degree of reduction became progressively more pronounced from the index to the
      little fingers (12%, 18%, 24% and 25%, respectively) and was similar for the
      dominant and non-dominant hands. This information may have clinical application
      when counselling patients regarding fusion of the distal interphalangeal joint of
      the fingers.

PMID- 29587605
TI  - Chondritis of the ear after docetaxel-carboplatin chemotherapy.
AB  - Docetaxel, derived from the yew tree, belongs to the taxane family of
      medications. It works by disrupting the normal function of microtubules, thereby
      stopping cell division. Docetaxel is used in the treatment of ovarian, breast,
      esophageal, gastric, prostate, lung, and head and neck cancers. Common side
      effects include hair loss, low blood cell counts, peripheral neuropathy,
      vomiting, and muscle pain. Auricular chondritis with ear deformity has not been
      reported previously as a side effect of docetaxel. In this paper, we present the
      case of a 64-year-old male patient with chondritis accompanied by ear deformity
      that developed due to docetaxel-carboplatin chemotherapy for non-small cell lung
      cancer.

PMID- 29587606
TI  - A response to the letter to the editor on Shaikh et al. Aplastic anemia secondary
      to propylthiouracil: A rare and life-threatening adverse effect.

PMID- 29587607
TI  - Assessment of bleeding incidences associated with rivaroxaban therapy in adults
      with solid tumors.
AB  - PURPOSE: Report bleeding incidences associated with rivaroxaban in adult patients
      with solid tumor malignancies requiring anticoagulation therapy. METHODS: This
      retrospective review was conducted at Indiana University Health, University
      Hospital and the Simon Cancer Center in Indianapolis, IN from January 2013 -
      February 2016. Patients were included if they had a solid tumor malignancy and
      prescribed rivaroxaban. Data were collected on 144 patients. Major bleeding was
      defined as bleeding requiring treatment (local, systemic treatment, blood cell
      transfusions) or hospitalization and minor bleeding was defined as bleeding not
      requiring treatment or hospitalization. RESULTS: Sixty-four (44%) patients
      experienced bleeding while on rivaroxaban. There were six cancer types that had a
      higher incidence of bleeding: bladder, breast, melanoma, pancreas, prostate, and
      renal cell cancers; 40% (6/15) of patients with bladder cancer experienced
      bleeding; 54% (7/13) with breast cancer experienced bleeding; 40% (4/10) of
      patients with melanoma experienced bleeding; 58% (11/19) of patients with
      pancreatic cancer experienced bleeding; 45% (10/22) of patients with prostate
      cancer experienced bleeding; and 56% (5/9) of patients with renal cell carcinoma
      experienced bleeding. No other data collected identified increased incidence of
      bleeding. CONCLUSIONS: Patients on rivaroxaban with a diagnosis of bladder,
      breast, melanoma, pancreas, prostate, or renal cell cancers had a higher
      incidence of bleeding compared to other solid tumors. Major bleeding was higher
      in bladder, breast, pancreas, and renal cell carcinomas, while minor bleeding was
      higher in patients with melanoma and prostate cancer.

PMID- 29587608
TI  - A pilot study to assess the pharmacy impact of implementing a chemotherapy
      induced nausea or vomiting collaborative disease therapy management in the
      outpatient oncology clinics.
AB  - Background Collaborative drug therapy management is a formal partnership between
      a pharmacist and physician to allow the pharmacist to manage a patient's drug
      therapy. Literature supports collaborative disease therapy management can improve
      patient outcomes, improve medication adherence, enhance medication safety, and
      positively influence healthcare expenditures. Chemotherapy induced nausea or
      vomiting is considered one of the most distressing and feared adverse events
      among patients receiving chemotherapy. Chemotherapy induced nausea or vomiting
      can impact a patient's quality of life and may affect compliance with the
      treatment plan. Purpose The objective of this pilot study was to determine the
      pharmacy impact of implementing a chemotherapy induced nausea or vomiting
      collaborative disease therapy management protocol in the outpatient oncology
      clinics at a National Cancer Institute (NCI)-designated cancer center associated
      with an academic medical center. The primary endpoint was to determine the number
      and type of chemotherapy induced nausea or vomiting clinical interventions made
      by the oncology pharmacists. Secondary endpoints included comparing patient's
      Multinational Association for Supportive Care in Cancer scores and revenue of
      pharmacists' services. Methods The credentialed oncology pharmacists were
      consulted by an oncologist to manage chemotherapy induced nausea or vomiting.
      Patients were included in the chemotherapy induced nausea or vomiting
      collaborative disease therapy management if they were seen in an outpatient
      oncology clinic from October 2016 to January 2017 and had a referral from a
      qualified provider to help manage chemotherapy induced nausea or vomiting.
      Patients admitted to the hospital at the time of consult were excluded from the
      study. The pharmacists interviewed patients and provided recommendations. The
      pharmacists followed up with the patient via a telephone call or during the next
      scheduled clinic visit to assess their symptoms. Results The chemotherapy induced
      nausea or vomiting collaborative disease therapy management pilot study was
      implemented in October 2016. From October 2016 to January 2017, there were 45
      consults for the management of chemotherapy induced nausea or vomiting. The
      pharmacists made 188 clinical interventions, which included addition of new
      medications (37%), patient education (34%), deletion of medications (10%),
      changing a dose/duration/frequency (8%), and other interventions (11%).
      Multinational Association for Supportive Care in Cancer symptom scores were
      available for 5 patients, in which all showed improvements from baseline with the
      pharmacists' clinical interventions. Conclusions The implementation of our
      chemotherapy induced nausea or vomiting collaborative disease therapy management
      pilot study has shown favorable results after a 4-month evaluation period. The
      pharmacists have made a substantial number of clinical interventions and provided
      patient education to patients undergoing chemotherapy.

PMID- 29587609
TI  - The challenges of palliative care for those with neurological diseases.

PMID- 29587610
TI  - NGS Analysis of Human Embryo Culture Media Reveals miRNAs of Extra Embryonic
      Origin.
AB  - Our objective in this work was to isolate, identify, and compare micro-RNAs
      (miRNAs) found in spent culture media of euploid and aneuploid in vitro
      fertilization (IVF) embryos. Seventy-two embryos from 62 patients were collected,
      and their spent media were retained. A total of 108 spent conditioned media
      samples were analyzed (n = 36 day 3 euploid embryos, n = 36 day 3 aneuploid
      embryos, and n = 36 matched control media). Fifty hed-control media embryos were
      analyzed using next-generation sequencing (NGS) technology. We detected 53 known
      human miRNAs present in the spent conditioned media of euploid and aneuploid IVF
      embryos. miR-181b-5p and miR-191-5p were found the most represented. We validated
      our results by quantitative polymerase chain reaction (qPCR), but no significant
      results were obtained between the groups. In conclusion, we obtained the list of
      miRNAs present in the spent conditioned media from euploid and aneuploid IVF
      embryos, but our data suggest that these miRNAs could have a nonembryonic origin.

PMID- 29587611
TI  - Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of
      Endometriosis.
AB  - Endometriosis is a chronic inflammatory and estrogen-dependent disease that
      causes pain and infertility in reproductive-aged women. Due to the delay in
      diagnosis, there is a pressing need for accurate biomarkers. Detection of serum
      noncoding RNA molecules such as microRNAs (miRNAs) shows promise as a noninvasive
      diagnostic strategy; we previously identified miRNAs that are highly sensitive
      and specific biomarkers for the disease. In this study, we investigate the
      expression of these miRNAs in a nonhuman primate model of endometriosis. As part
      of a pilot study evaluating simvastatin for the treatment of endometriosis, the
      disease was induced in 16 baboons by induction laparoscopy and the animals were
      divided into 2 groups. One group was treated with simvastatin for 90 days, while
      the second group received vehicle only. Endometriosis was evaluated after 3
      months by laparoscopy. Serum samples were analyzed for 9 circulating miRNAs using
      quantitative real time-polymerase chain reaction, focusing on the miRNAs we found
      to be dysregulated in human endometriosis. In the simvastatin-treated
      endometriosis group, levels of miR-150-5p and miR-451a were decreased, while miR
      3613-5p levels were increased compared to the untreated endometriosis group. The
      changes in circulating miRNA expression patterns parallel our previous results in
      human patients and show that specific miRNAs correlate with endometriosis
      severity and reverted toward control expression levels after simvastatin
      treatment. This is the first report showing serum miRNA expression normalized in
      response to endometriosis treatment, supporting the potential for this class of
      biomarkers to be used both to diagnose endometriosis and to monitor its
      progression and response to therapy.

PMID- 29587612
TI  - Regulatory Functions of MicroRNAs in Male Reproductive Health: A New Approach to
      Understanding Male Infertility.
AB  - MicroRNAs (miRNAs) are a novel class of small noncoding RNAs (ncRNAs) that play
      critical roles in regulation of gene expression, especially at
      posttranscriptional level. Over the past decade, the degree to which miRNAs are
      involved in male infertility has become clear. They are expressed in a cell- or
      phase-specific manner during spermatogenesis and play crucial role in male
      reproductive health. Therefore, dysregulation of miRNAs in testicular cells can
      be considered as a molecular basis for reproductive failure and male infertility.
      The abnormal expression pattern of miRNAs can be transmitted to the offspring via
      assisted reproductive techniques (ART) and results in the birth of children with
      a higher risk of infertility, congenital abnormalities, and morbidity. This
      review expounds on the miRNAs reported to play essential roles in somatic cells
      development, germ cells differentiation, steroidogenesis, normal spermatogenesis,
      sperm maturation, and male infertility, as well as emphasizes their importance as
      minimally invasive biomarkers of male infertility.

PMID- 29587614
TI  - Pharmacogenomics in IVF: A New Era in the Concept of Personalized Medicine.
AB  - Pharmacogenomics is a promising approach in the field of individualized medicine
      in in vitro fertilization (IVF) treatment that aims to develop optimized
      pharmacotherapy depending on the genetic background of each infertile woman, thus
      to ensure maximum effectiveness of the medication used, with minimal side
      effects. The unique genetic information of each infertile woman, in combination
      with already known, as well as new predictors of ovarian response and the
      progress of pharmacoepigenomics, is anticipated to greatly benefit the process of
      controlled ovarian stimulation. This review analyses current data on IVF
      pharmacogenomics, a new approach that is gradually moving to the frontline of
      modern IVF treatment.

PMID- 29587613
TI  - G-Protein-Coupled Receptor CXCR7 Is Overexpressed in Human and Murine
      Endometriosis.
AB  - Endometriosis is a chronic inflammatory disease. Dysfunctional regulation of
      chemokines and chemokine receptors is a crucial aspect of endometriosis
      pathogenesis. Chemokine G-protein-coupled receptors (GPCRs) are important drug
      targets that regulate inflammation and immunity. Recently, CXCR7, a C-X-C motif
      containing GPCR, has been identified as a receptor for chemokine ligand CXCL12,
      one of the best characterized chemokines for cell trafficking, angiogenesis, and
      cell proliferation in cancer and inflammation. Here, we investigated the
      expression and localization of CXCR7 in human endometriosis and a murine model of
      the disease. Normal endometrial epithelium and stroma showed undetectable or very
      low expression of CXCR7, without any significant changes across phases of the
      menstrual cycle in humans. CXCR7 is significantly upregulated in endometriosis,
      showing higher staining in glands and in associated vessels. The mouse model
      recapitulated the human findings. In conclusion, overexpression of CXCR7 in
      different cellular populations of endometriosis microenvironment may play a role
      in the pathogenesis and represent a novel target for treatment.

PMID- 29587615
TI  - 25-Hydroxyvitamin D Serum Levels and Endometriosis: Results of a Case-Control
      Study.
AB  - The immunomodulatory, anti-inflammatory, and antiproliferative properties of
      vitamin D have laid the basis for a possible function of this prohormone in the
      pathogenesis of endometriosis. The aim of this case-control study was to
      investigate vitamin D status, by measuring 25-hydroxyvitamin D [25(OH)D] serum
      levels, in women with and without endometriosis. Only Italian women of Caucasian
      origin aged between 18 and 45 years were deemed eligible. Enrollment was limited
      to the period October to May. Cases and controls were matched for month of
      recruitment and secondarily for age and parity. Overall, 434 women were enrolled
      (endometriosis n = 217; controls n = 217). The group of cases included 127 women
      with ovarian endometrioma and 90 patients with deep endometriosis. Mean (standard
      deviation) levels of 25(OH)D in women with and without endometriosis were 17.9
      (7.0) ng/mL and 18.4 (7.6) ng/mL, respectively ( P = .46). Analyzing the two
      endometriosis subgroups separately, no statistically significant differences
      emerged (18.7 [7.4] ng/mL in deep endometriosis group vs 17.3 [6.6] ng/mL in
      women with ovarian endometrioma; P = .14). Comparing the subgroup of women with
      deep endometriosis with paired controls, no differences occurred (18.7 [7.4]
      ng/mL vs 18.5 [7.7] ng/mL, P = .80). Similar data emerged when performing the
      same analysis for ovarian endometriomas (17.4 [6.6] ng/mL vs 18.3 [7.6] ng/mL, P
      = .23). The results of the present case-control study do not support an
      association between serum vitamin D levels and different phenotypes of
      endometriosis.

PMID- 29587616
TI  - Molecular Mechanisms of Prophase I Meiotic Arrest Maintenance and Meiotic
      Resumption in Mammalian Oocytes.
AB  - Mechanisms of meiotic prophase I arrest maintenance (germinal vesicle [GV] stage)
      and meiotic resumption (germinal vesicle breakdown [GVBD] stage) in mammalian
      oocytes seem to be very complicated. These processes are regulated via multiple
      molecular cascades at transcriptional, translational, and posttranslational
      levels, and many of them are interrelated. There are many molecular cascades of
      meiosis maintaining and meiotic resumption in oocyte which are orchestrated by
      multiple molecules produced by pituitary gland and follicular cells. Furthermore,
      many of these molecular cascades are duplicated, thus ensuring the stability of
      the entire system. Understanding mechanisms of oocyte maturation is essential to
      assess the oocyte status, develop effective protocols of oocyte in vitro
      maturation, and design novel contraceptive drugs. Mechanisms of meiotic arrest
      maintenance at prophase I and meiotic resumption in mammalian oocytes are covered
      in the present article.

PMID- 29587617
TI  - Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine
      Amnion.
AB  - Vascular endothelial growth factor (VEGF) has been proposed as an important
      regulator of amniotic fluid absorption across the amnion into the fetal
      vasculature on the surface of the placenta. However, the activators of VEGF
      expression and action in the amnion have not been identified. Using the pregnant
      sheep model, we aimed to investigate the presence of the retinoic acid (RA)
      pathway in ovine amnion and to determine its effect on VEGF expression. Further,
      we explored relationships between RA receptors and VEGF and tested the hypothesis
      that RA modulates intramembranous absorption (IMA) through induction of amnion
      VEGF in sheep fetuses subjected to altered IMA rates. Our study showed that RA
      receptor isoforms were expressed in sheep amnion, and RA response elements
      (RAREs) were identified in ovine RARbeta and VEGF gene promoters. In ovine amnion
      cells, RA treatment upregulated RARbeta messenger RNA (mRNA) and increased VEGF
      transcript levels. In sheep fetuses, increases in IMA rate was associated with
      elevated VEGF mRNA levels in the amnion but not in the chorion. Further, RARbeta
      mRNA was positively correlated with VEGF mRNA levels in the amnion and not
      chorion. We conclude that an RA pathway is present in ovine fetal membranes and
      that RA is capable of inducing VEGF. The finding of a positive relationship
      between amnion VEGF and RARbeta during altered IMA rate suggests that the
      retinoid pathway may play a role through VEGF in regulating intramembranous
      transport across the amnion.

PMID- 29587618
TI  - Two approaches to 14,15-secoergostane intermediates for the synthesis of
      strophasterols.
AB  - Two protected 14,15-secoergostane derivatives suitable as pivotal intermediates
      for the synthesis of strophasterols A and B, anti-MRSA and neuronal cell
      protecting natural products bearing a recently discovered strophastane skeleton,
      have been synthesized by two different routes. The first approach employed an
      oxidative cleavage of an alpha-hydroxy ketone intermediate with the Jones reagent
      as the key step to reach the targeted secoergostane from ergosterol in ten steps.
      In the second approach, an unprecedented reaction cascade composed of four
      reactions enabled us to obtain the secoergostane more efficiently in six steps.

PMID- 29587619
TI  - Medical Marijuana Update.
AB  - The majority of states now allow medical marijuana, and recent court decisions
      could influence workplace practice concerning its use.

PMID- 29587621
TI  - Comment on "The Opioid Epidemic".

PMID- 29587622
TI  - DS-7250, a Diacylglycerol Acyltransferase 1 Inhibitor, Enhances Hepatic Steatosis
      in Zucker Fatty Rats via Upregulation of Fatty Acid Synthesis.
AB  - Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride
      synthesis. Since Dgat1-/- mice fed a high-fat diet (HFD) are resistant to hepatic
      steatosis, DGAT1 inhibitors are expected to have antifatty liver effects. To
      evaluate the hepatic effects of DS-7250, a selective DGAT1 inhibitor, vehicle or
      10 mg/kg of DS-7250 was administered orally to male Fisher 344 (F344) and Zucker
      fatty (ZF) rats fed a standard diet or HFD for 14 or 28 days. ZF rats showed
      slight hepatic steatosis regardless of feeding conditions. DS-7250 exacerbated
      hepatic steatosis in ZF rats fed an HFD compared with the vehicle control.
      Hepatic steatosis did not occur in F344 rats fed an HFD, in which systemic
      exposures of DS-7250 were comparable to those in ZF rats. There was a higher
      expression of genes involved in lipid uptake and fatty acid synthesis in ZF rats
      compared to F344 rats under HFD conditions. DS-7250 upregulated key genes
      involved in de novo lipogenesis, which causes hepatic steatosis independently of
      DGAT1, in ZF rats fed an HFD compared with the vehicle control. These data
      suggest that ZF rats were more susceptible to hepatic steatosis due to their
      genetic characteristics and DS-7250 exacerbated hepatic steatosis independently
      of DGAT1.

PMID- 29587623
TI  - Olive leaf extract prevents cartilage degeneration in osteoarthritis of STR/ort
      mice.
AB  - The chondroprotective effect of olive leaf extract (OLE) on knee osteoarthritis
      (OA) was studied with STR/ort mice (n = 5). OLE was administrated with a dosage
      of 100 mg/kg for 8 weeks and the OA severity score of hind limb knee joints was
      then measured. The Mankin scores of the knee joints of the non-OA control group,
      OA control group and OLE-treated group were 3.50, 11.13 and 7.20, respectively.
      This suggests that oral OLE supplements help prevent cartilage degeneration in
      STR/ort mice. In vitro, the synthesis of high molecular weight hyaluronan in
      synovial cells (HIG-82) was increased by OLE stimulation. This suggests that OLE
      modulates hyaluronan metabolism in synovial cells and improves OA symptoms. Our
      findings indicate that OLE intake inhibits cartilage destruction by increasing
      high molecular weight hyaluronan and thus preventing OA progress.

PMID- 29587624
TI  - Diabetes classification model based on boosting algorithms.
AB  - BACKGROUND: Diabetes mellitus is a common and complicated chronic lifelong
      disease. Hence, it is of high clinical significance to find the most relevant
      clinical indexes and to perform efficient computer-aided pre-diagnoses and
      diagnoses. RESULTS: Non-parametric statistical testing is performed on hundreds
      of medical measurement index results between diabetic and non-diabetic
      populations. Two common boosting algorithms, Adaboost.M1 and LogitBoost, are
      selected to establish a machine model for diabetes diagnosis based on these
      clinical test data, involving a total of 35,669 individuals. The machine
      classification models built by these two algorithms have very good classification
      ability. Here, the LogitBoost classification model is slightly better than the
      Adaboost.M1 classification model. The overall accuracy of the LogitBoost
      classification model reached 95.30% when using 10-fold cross validation. The true
      positive, true negative, false positive, and false negative rates of the binary
      classification model were 0.921, 0.969, 0.031, and 0.079, respectively, and the
      area under the receiver operating characteristic curve reached 0.99. CONCLUSIONS:
      The boosting algorithms show excellent performance for the diabetes
      classification models based on clinical medical data. The coefficient matrix of
      the original data is a sparse matrix, because some of the test results were
      missing, including some that were directly related to disease diagnosis.
      Therefore, the model is robust and has a degree of pre-diagnosis function. In the
      process of selecting the preferred test items, the most statistically significant
      discriminating factors between the diabetic and general populations were obtained
      and can be used as reference risk factors for diabetes mellitus.

PMID- 29587625
TI  - The effects of intranasal oxytocin on reward circuitry responses in children with
      autism spectrum disorder.
AB  - BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social
      communication functioning of individuals with autism spectrum disorder (ASD) and,
      thus, has received considerable interest as a potential ASD therapeutic agent.
      Although preclinical research indicates that OT modulates the functional output
      of the mesocorticolimbic dopamine system that processes rewards, no clinical
      brain imaging study to date has examined the effects of OT on this system using a
      reward processing paradigm. To address this, we used an incentive delay task to
      examine the effects of a single dose of intranasal OT, versus placebo (PLC), on
      neural responses to social and nonsocial rewards in children with ASD. METHODS:
      In this placebo-controlled double-blind study, 28 children and adolescents with
      ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after
      intranasal OT administration and one after PLC administration. During both
      scanning sessions, participants completed social and nonsocial incentive delay
      tasks. Task-based neural activation and connectivity were examined to assess the
      impact of OT relative to PLC on mesocorticolimbic brain responses to social and
      nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared
      the OT and PLC conditions. During nonsocial reward anticipation, there was
      greater activation in the right nucleus accumbens (NAcc), left anterior cingulate
      cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal
      cortex, and right frontal pole (FP) during the OT condition relative to PLC.
      Alternatively, during social reward anticipation and outcomes, there were no
      significant increases in brain activation during the OT condition relative to
      PLC. A Treatment Group * Reward Condition interaction revealed relatively greater
      activation in the right NAcc, right caudate nucleus, left ACC, and right OFC
      during nonsocial relative to social reward anticipation during the OT condition
      relative to PLC. Additionally, these analyses revealed greater activation during
      nonsocial reward outcomes during the OT condition relative to PLC in the right
      OFC and left FP. Finally, functional connectivity analyses generally revealed
      changes in frontostriatal connections during the OT condition relative to PLC in
      response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of
      intranasal OT administration on mesocorticolimbic brain systems that process
      rewards in ASD were observable primarily during the processing of nonsocial
      incentive salience stimuli. These findings have implications for understanding
      the effects of OT on neural systems that process rewards, as well as for
      experimental trials of novel ASD treatments developed to ameliorate social
      communication impairments in ASD.

PMID- 29587627
TI  - Obtaining insights from high-dimensional data: sparse principal covariates
      regression.
AB  - BACKGROUND: Data analysis methods are usually subdivided in two distinct classes:
      There are methods for prediction and there are methods for exploration. In
      practice, however, there often is a need to learn from the data in both ways. For
      example, when predicting the antibody titers a few weeks after vaccination on the
      basis of genomewide mRNA transcription rates, also mechanistic insights about the
      effect of vaccinations on the immune system are sought. Principal covariates
      regression (PCovR) is a method that combines both purposes. Yet, it misses
      insightful representations of the data as these include all the variables.
      RESULTS: Here, we propose a sparse extension of principal covariates regression
      such that the resulting solutions are based on an automatically selected subset
      of the variables. Our method is shown to outperform competing methods like sparse
      principal components regression and sparse partial least squares in a simulation
      study. Furthermore good performance of the method is illustrated on publicly
      available data including antibody titers and genomewide transcription rates for
      subjects vaccinated against the flu: the selected genes by sparse PCovR are higly
      enriched for immune related terms and the method predicts the titers for an
      independent test sample well. In comparison, no significantly enriched terms were
      found for the genes selected by sparse partial least squares and out-of-sample
      prediction was worse. CONCLUSIONS: Sparse principal covariates regression is a
      promising and competitive tool for obtaining insights from high-dimensional data.
      AVAILABILITY: The source code implementing our proposed method is available from
      GitHub, together with all scripts used to extract, pre-process, analyze, and post
      process the data: https://github.com/katrijnvandeun/SPCovR .

PMID- 29587626
TI  - Diversity and distribution of Wolbachia in relation to geography, host plant
      affiliation and life cycle of a heterogonic gall wasp.
AB  - BACKGROUND: The maternally inherited endosymbiont Wolbachia is widespread in
      arthropods and nematodes and can play an important role in the ecology and
      evolution of its host through reproductive manipulation. Here, we survey
      Wolbachia in Belonocnema treatae, a widely distributed North American cynipid
      gall forming wasp that exhibits regional host specialization on three species of
      oaks and alternation of sexually and asexually reproducing generations. We
      investigated whether patterns of Wolbachia infection and diversity in B. treatae
      are associated with the insect's geographic distribution, host plant association,
      life cycle, and mitochondrial evolutionary history. RESULTS: Screening of 463
      individuals from 23 populations including sexual and asexual generations from all
      three host plants across the southern U.S. showed an average infection rate of
      56% with three common Wolbachia strains: wTre1-3 and an additional rare variant
      wTre4. Phylogenetic analysis based on wsp showed that these strains are unrelated
      and likely independently inherited. We found no difference in Wolbachia infection
      frequency among host plant associated populations or between the asexual and
      sexual generations, or between males and females of the sexual generation.
      Partially incomplete Wolbachia transmission rates might explain the occurrence of
      uninfected individuals. A parallel analysis of the mitochondrial cytochrome
      oxidase I gene in B. treatae showed high mtDNA haplotype diversity in both
      infected and uninfected populations suggesting an ancestral infection by
      Wolbachia as well as a clear split between eastern and western B. treatae mtDNA
      clades with a sequence divergence of > 6%. The strain wTre1 was present almost
      exclusively in the western clade while wTre2 and wTre3 occur almost exclusively
      in eastern populations. In contrast, the same strains co-occur as double
      infections in Georgia and triple-infections in two populations in central
      Florida. CONCLUSIONS: The diversity of Wolbachia across geographically and
      genetically distinct populations of B. treatae and the co-occurrence of the same
      strains within three populations highlights the complex infection dynamics in
      this system. Moreover, the association of distinct Wolbachia strains with
      mitochondrial haplotypes of its host in populations infected by different
      Wolbachia strains suggests a potential role of the endosymbiont in reproductive
      isolation in B. treatae.

PMID- 29587628
TI  - A method combining a random forest-based technique with the modeling of linkage
      disequilibrium through latent variables, to run multilocus genome-wide
      association studies.
AB  - BACKGROUND: Genome-wide association studies (GWASs) have been widely used to
      discover the genetic basis of complex phenotypes. However, standard single-SNP
      GWASs suffer from lack of power. In particular, they do not directly account for
      linkage disequilibrium, that is the dependences between SNPs (Single Nucleotide
      Polymorphisms). RESULTS: We present the comparative study of two multilocus GWAS
      strategies, in the random forest-based framework. The first method, T-Trees, was
      designed by Botta and collaborators (Botta et al., PLoS ONE 9(4):e93379, 2014).
      We designed the other method, which is an innovative hybrid method combining T
      Trees with the modeling of linkage disequilibrium. Linkage disequilibrium is
      modeled through a collection of tree-shaped Bayesian networks with latent
      variables, following our former works (Mourad et al., BMC Bioinformatics
      12(1):16, 2011). We compared the two methods, both on simulated and real data.
      For dominant and additive genetic models, in either of the conditions simulated,
      the hybrid approach always slightly performs better than T-Trees. We assessed
      predictive powers through the standard ROC technique on 14 real datasets. For 10
      of the 14 datasets analyzed, the already high predicted power observed for T
      Trees (0.910-0.946) can still be increased by up to 0.030. We also assessed
      whether the distributions of SNPs' scores obtained from T-Trees and the hybrid
      approach differed. Finally, we thoroughly analyzed the intersections of top 100
      SNPs output by any two or the three methods amongst T-Trees, the hybrid approach,
      and the single-SNP method. CONCLUSIONS: The sophistication of T-Trees through
      finer linkage disequilibrium modeling is shown beneficial. The distributions of
      SNPs' scores generated by T-Trees and the hybrid approach are shown statistically
      different, which suggests complementary of the methods. In particular, for 12 of
      the 14 real datasets, the distribution tail of highest SNPs' scores shows larger
      values for the hybrid approach. Thus are pinpointed more interesting SNPs than by
      T-Trees, to be provided as a short list of prioritized SNPs, for a further
      analysis by biologists. Finally, among the 211 top 100 SNPs jointly detected by
      the single-SNP method, T-Trees and the hybrid approach over the 14 datasets, we
      identified 72 and 38 SNPs respectively present in the top25s and top10s for each
      method.

PMID- 29587629
TI  - Comparative analysis of FKBP family protein: evaluation, structure, and function
      in mammals and Drosophila melanogaster.
AB  - BACKGROUND: FK506-binding proteins (FKBPs) have become the subject of
      considerable interest in several fields, leading to the identification of several
      cellular and molecular pathways in which FKBPs impact prenatal development and
      pathogenesis of many human diseases. MAIN BODY: This analysis revealed
      differences between how mammalian and Drosophila FKBPs mechanisms function in
      relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that
      could be used to design insect-specific pesticides. (1) Molecular phylogenetic
      analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs
      share homology with the human FKBP12. This indicates a close evolutionary
      relationship, and possible origination from a common ancestor. (2) The known
      FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain
      that mediates immune suppression through inhibition of calcineurin. The dFKBP59,
      CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at
      the C-terminus, which regulates transcription and protein transportation. (3)
      FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5,
      function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90
      heterocomplexes. These immunophilins are potential drug targets in pathways
      associated with normal physiology and may be used to treat a variety of steroid
      based diseases by targeting exocytic/endocytic cycling and vesicular trafficking.
      (4) By associating with presinilin, a critical component of the Notch signaling
      pathway, FKBP14 is a downstream effector of Notch activation at the membrane.
      Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA
      pathway, playing a crucial role in both germ cells and ovarian somas. Mutations
      in or silencing of dFKBPs lead to early embryonic lethality in Drosophila.
      Therefore, further understanding the mechanisms of FK506 and rapamycin binding to
      immunophilin FKBPs in endocrine, cardiovascular, and neurological function in
      both mammals and Drosophila would provide prospects in generating unique, insect
      specific therapeutics targeting the above cellular signaling pathways.
      CONCLUSION: This review will evaluate the functional roles of FKBP family
      proteins, and systematically summarize the similarities and differences between
      FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular
      signaling pathways will also be discussed.

PMID- 29587630
TI  - Notos - a galaxy tool to analyze CpN observed expected ratios for inferring DNA
      methylation types.
AB  - BACKGROUND: DNA methylation patterns store epigenetic information in the vast
      majority of eukaryotic species. The relatively high costs and technical
      challenges associated with the detection of DNA methylation however have created
      a bias in the number of methylation studies towards model organisms.
      Consequently, it remains challenging to infer kingdom-wide general rules about
      the functions and evolutionary conservation of DNA methylation. Methylated
      cytosine is often found in specific CpN dinucleotides, and the frequency
      distributions of, for instance, CpG observed/expected (CpG o/e) ratios have been
      used to infer DNA methylation types based on higher mutability of methylated CpG.
      RESULTS: Predominantly model-based approaches essentially founded on mixtures of
      Gaussian distributions are currently used to investigate questions related to the
      number and position of modes of CpG o/e ratios. These approaches require the
      selection of an appropriate criterion for determining the best model and will
      fail if empirical distributions are complex or even merely moderately skewed. We
      use a kernel density estimation (KDE) based technique for robust and precise
      characterization of complex CpN o/e distributions without a priori assumptions
      about the underlying distributions. CONCLUSIONS: We show that KDE delivers robust
      descriptions of CpN o/e distributions. For straightforward processing, we have
      developed a Galaxy tool, called Notos and available at the ToolShed, that
      calculates these ratios of input FASTA files and fits a density to their
      empirical distribution. Based on the estimated density the number and shape of
      modes of the distribution is determined, providing a rational for the prediction
      of the number and the types of different methylation classes. Notos is written in
      R and Perl.

PMID- 29587631
TI  - Integrative analysis reveals ncRNA-mediated molecular regulatory network driving
      secondary hair follicle regression in cashmere goats.
AB  - BACKGROUND: Cashmere is a keratinized product derived from the secondary hair
      follicles (SHFs) of cashmere goat skins. The cashmere fiber stops growing
      following the transition from the actively proliferating anagen stage to the
      apoptosis-driven catagen stage. However, little is known regarding the molecular
      mechanisms responsible for the occurrence of apoptosis in SHFs, especially as
      pertains to the role of non-coding RNAs (ncRNAs) and their interactions with
      other molecules. Hair follicle (HF) degeneration is caused by localized apoptosis
      in the skin, while anti-apoptosis pathways may coexist in adjacent HFs. Thus,
      elucidating the molecular interactions responsible for apoptosis and anti
      apoptosis in the skin will provide insights into HF regression. RESULTS: We used
      multiple-omics approaches to systematically identify long non-coding RNAs
      (lncRNAs), microRNAs (miRNAs) and mRNAs expressed in cashmere goat skins in two
      crucial phases (catagen vs. anagen) of HF growth. Skin samples were collected
      from three cashmere goats at the anagen (September) and catagen (February)
      stages, and six lncRNA libraries and six miRNA libraries were constructed for
      further analysis. We identified 1122 known and 403 novel lncRNAs in the goat
      skins, 173 of which were differentially expressed between the anagen and catagen
      stages. We further identified 3500 gene-encoding transcripts that were
      differentially expressed between these two phases. We also identified 411 known
      miRNAs and 307 novel miRNAs, including 72 differentially expressed miRNAs. We
      further investigated the target genes of lncRNAs via both cis- and trans
      regulation during HF growth. Our data suggest that lncRNAs and miRNAs act
      synergistically in the HF growth transition, and the catagen inducer factors
      (TGFbeta1 and BDNF) were regulated by miR-873 and lnc108635596 in the lncRNA
      miRNA-mRNA networks. CONCLUSION: This study enriches the repertoire of ncRNAs in
      goats and other mammals, and contributes to a better understanding of the
      molecular mechanisms of ncRNAs involved in the regulation of HF growth and
      regression in goats and other hair-producing species.

PMID- 29587632
TI  - Transcriptomic profiling of tall fescue in response to heat stress and improved
      thermotolerance by melatonin and 24-epibrassinolide.
AB  - BACKGROUND: Tall fescue is a widely used cool season turfgrass and relatively
      sensitive to high temperature. Chemical compounds like melatonin (MT) and 24
      epibrassinolide (EBL) have been reported to improve plant heat stress tolerance
      effectively. RESULTS: In this study, we reported that MT and EBL pretreated tall
      fescue seedlings showed decreased reactive oxygen species (ROS), electrolyte
      leakage (EL) and malondialdehide (MDA), but increased chlorophyll (Chl), total
      protein and antioxidant enzyme activities under heat stress condition, resulting
      in improved plant growth. Transcriptomic profiling analysis showed that 4311 and
      8395 unigenes were significantly changed after 2 h and 12 h of heat treatments,
      respectively. Among them, genes involved in heat stress responses, DNA, RNA and
      protein degradation, redox, energy metabolisms, and hormone metabolism pathways
      were highly induced after heat stress. Genes including FaHSFA3, FaAWPM and
      FaCYTC2 were significantly upregulated by both MT and EBL treatments, indicating
      that these genes might function as the putative target genes of MT and EBL.
      CONCLUSIONS: These findings indicated that heat stress caused extensively
      transcriptomic reprogramming of tall fescue and exogenous application of MT and
      EBL effectively improved thermotolerance in tall fescue.

PMID- 29587633
TI  - The complete mitochondrial genome of the hermaphroditic freshwater mussel
      Anodonta cygnea (Bivalvia: Unionidae): in silico analyses of sex-specific ORFs
      across order Unionoida.
AB  - BACKGROUND: Doubly uniparental inheritance (DUI) of mitochondrial DNA in bivalves
      is a fascinating exception to strictly maternal inheritance as practiced by all
      other animals. Recent work on DUI suggests that there may be unique regions of
      the mitochondrial genomes that play a role in sex determination and/or sexual
      development in freshwater mussels (order Unionoida). In this study, one complete
      mitochondrial genome of the hermaphroditic swan mussel, Anodonta cygnea, is
      sequenced and compared to the complete mitochondrial genome of the gonochoric
      duck mussel, Anodonta anatina. An in silico assessment of novel proteins found
      within freshwater bivalve species (known as F-, H-, and M-open reading frames or
      ORFs) is conducted, with special attention to putative transmembrane domains
      (TMs), signal peptides (SPs), signal cleavage sites (SCS), subcellular
      localization, and potential control regions. Characteristics of TMs are also
      examined across freshwater mussel lineages. RESULTS: In silico analyses suggests
      the presence of SPs and SCSs and provides some insight into possible function(s)
      of these novel ORFs. The assessed confidence in these structures and functions
      was highly variable, possibly due to the novelty of these proteins. The number
      and topology of putative TMs appear to be maintained among both F- and H-ORFs,
      however, this is not the case for M-ORFs. There does not appear to be a typical
      control region in H-type mitochondrial DNA, especially given the loss of tandem
      repeats in unassigned regions when compared to F-type mtDNA. CONCLUSION: In
      silico analyses provides a useful tool to discover patterns in DUI and to
      navigate further in situ analyses related to DUI in freshwater mussels. In situ
      analysis will be necessary to further explore the intracellular localizations and
      possible role of these open reading frames in the process of sex determination in
      freshwater mussel.

PMID- 29587634
TI  - High-throughput detection of RNA processing in bacteria.
AB  - BACKGROUND: Understanding the RNA processing of an organism's transcriptome is an
      essential but challenging step in understanding its biology. Here we investigate
      with unprecedented detail the transcriptome of Pseudomonas aeruginosa PAO1, a
      medically important and innately multi-drug resistant bacterium. We
      systematically mapped RNA cleavage and dephosphorylation sites that result in 5'
      monophosphate terminated RNA (pRNA) using monophosphate RNA-Seq (pRNA-Seq).
      Transcriptional start sites (TSS) were also mapped using differential RNA-Seq
      (dRNA-Seq) and both datasets were compared to conventional RNA-Seq performed in a
      variety of growth conditions. RESULTS: The pRNA-Seq library revealed known tRNA,
      rRNA and transfer-messenger RNA (tmRNA) processing sites, together with
      previously uncharacterized RNA cleavage events that were found disproportionately
      near the 5' ends of transcripts associated with basic bacterial functions such as
      oxidative phosphorylation and purine metabolism. The majority (97%) of the
      processed mRNAs were cleaved at precise codon positions within defined sequence
      motifs indicative of distinct endonucleolytic activities. The most abundant of
      these motifs corresponded closely to an E. coli RNase E site previously
      established in vitro. Using the dRNA-Seq library, we performed an operon analysis
      and predicted 3159 potential TSS. A correlation analysis uncovered 105
      antiparallel pairs of TSS that were separated by 18 bp from each other and were
      centered on single palindromic TAT(A/T)ATA motifs (likely - 10 promoter
      elements), suggesting that, consistent with previous in vitro experimentation,
      these sites can initiate transcription bi-directionally and may thus provide a
      novel form of transcriptional regulation. TSS and RNA-Seq analysis allowed us to
      confirm expression of small non-coding RNAs (ncRNAs), many of which are
      differentially expressed in swarming and biofilm formation conditions.
      CONCLUSIONS: This study uses pRNA-Seq, a method that provides a genome-wide
      survey of RNA processing, to study the bacterium Pseudomonas aeruginosa and
      discover extensive transcript processing not previously appreciated. We have also
      gained novel insight into RNA maturation and turnover as well as a potential
      novel form of transcription regulation. NOTE: All sequence data has been
      submitted to the NCBI sequence read archive. Accession numbers are as follows:
      [NCBI sequence read archive: SRX156386, SRX157659, SRX157660, SRX157661,
      SRX157683 and SRX158075]. The sequence data is viewable using Jbrowse on
      www.pseudomonas.com .

PMID- 29587635
TI  - Genome-wide transcriptional analyses in Anopheles mosquitoes reveal an unexpected
      association between salivary gland gene expression and insecticide resistance.
AB  - BACKGROUND: To combat malaria transmission, the Ugandan government has embarked
      upon an ambitious programme of indoor residual spraying (IRS) with a carbamate
      class insecticide, bendiocarb. In preparation for this campaign, we characterized
      bendiocarb resistance and associated transcriptional variation among Anopheles
      gambiae s.s. mosquitoes from two sites in Uganda. RESULTS: Gene expression in two
      mosquito populations displaying some resistance to bendiocarb (95% and 79% An.
      gambiae s.l. WHO tube bioassay mortality in Nagongera and Kihihi, respectively)
      was investigated using whole-genome microarrays. Significant overexpression of
      several genes encoding salivary gland proteins, including D7r2 and D7r4, was
      detected in mosquitoes from Nagongera. In Kihihi, D7r4, two detoxification
      associated genes (Cyp6m2 and Gstd3) and an epithelial serine protease were among
      the genes most highly overexpressed in resistant mosquitoes. Following the first
      round of IRS in Nagongera, bendiocarb-resistant mosquitoes were collected, and
      real-time quantitative PCR analyses detected significant overexpression of D7r2
      and D7r4 in resistant mosquitoes. A single nucleotide polymorphism located in a
      non-coding transcript downstream of the D7 genes was found at a significantly
      higher frequency in resistant individuals. In silico modelling of the interaction
      between D7r4 and bendiocarb demonstrated similarity between the insecticide and
      serotonin, a known ligand of D7 proteins. A meta-analysis of published microarray
      studies revealed a recurring association between D7 expression and insecticide
      resistance across Anopheles species and locations. CONCLUSIONS: A whole-genome
      microarray approach identified an association between novel insecticide
      resistance candidates and bendiocarb resistance in Uganda. In addition, a single
      nucleotide polymorphism associated with this resistance mechanism was discovered.
      The use of such impartial screening methods allows for discovery of resistance
      candidates that have no previously-ascribed function in insecticide binding or
      detoxification. Characterizing these novel candidates will broaden our
      understanding of resistance mechanisms and yield new strategies for combatting
      widespread insecticide resistance among malaria vectors.

PMID- 29587636
TI  - The attenuation of neurological injury from the use of simvastatin after spinal
      cord ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Spinal cord ischemic injury remains a serious complication of open
      surgical and endovascular aortic procedures. Simvastatin has been reported to be
      associated with neuroprotective effect after spinal cord ischemia-reperfusion
      (IR) injury. The aim of this study was to determine the therapeutic efficacy of
      starting simvastatin after spinal cord IR injury in a rat model. METHODS: In
      adult Sprague-Dawley rats, spinal cord ischemia was induced using a balloon
      tipped catheter placed in the descending thoracic aorta. The animals were then
      randomly divided into 4 groups: group A (control); group B (0.5 mg/kg
      simvastatin); group C (1 mg/kg simvastatin); and group D (10 mg/kg simvastatin).
      Simvastatin was administered orally upon reperfusion for 5 days. Neurological
      function of the hind limbs was evaluated for 7 days after reperfusion and
      recorded using a motor deficit score (MDS) (0: normal, 5: complete paraplegia).
      The number of normal motor neurons within the anterior horns of the spinal cord
      was counted after final MDS evaluation. Then, the spinal cord was harvested for
      histopathological examination. RESULTS: Group D showed a significantly lower MDS
      than the other groups at post-reperfusion day 1 and this trend was sustained
      throughout the study period. Additionally, a greater number of normal motor
      neurons was observed in group D than in other groups (group D 21.2 [3.2] vs.
      group A: 15.8 [4.2]; group B 15.4 [3.4]; and group C 15.5 [3.7]; P = 0.002).
      CONCLUSIONS: The results of the current study suggest that 10 mg/kg can
      significantly improve neurologic outcome by attenuating neurologic injury and
      restoring normal motor neurons after spinal cord IR injury.

PMID- 29587637
TI  - Combining QTL-seq and linkage mapping to fine map a wild soybean allele
      characteristic of greater plant height.
AB  - BACKGROUND: Plant height (PH) is an important agronomic trait and is closely
      related to yield in soybean [Glycine max (L.) Merr.]. Previous studies have
      identified many QTLs for PH. Due to the complex genetic background of PH in
      soybean, there are few reports on its fine mapping. RESULTS: In this study, we
      used a mapping population derived from a cross between a chromosome segment
      substitution line CSSL3228 (donor N24852 (G. Soja), a receptor NN1138-2 (G. max))
      and NN1138-2 to fine map a wild soybean allele of greater PH by QTL-seq and
      linkage mapping. We identified a QTL for PH in a 1.73 Mb region on soybean
      chromosome 13 through QTL-seq, which was confirmed by SSR marker-based classical
      QTL mapping in the mapping population. The linkage analysis showed that the QTLs
      of PH were located between the SSR markers BARCSOYSSR_13_1417 and
      BARCSOYSSR_13_1421 on chromosome 13, and the physical distance was 69.3 kb. RT
      PCR and sequence analysis of possible candidate genes showed that Glyma.13
      g249400 revealed significantly higher expression in higher PH genotypes, and the
      gene existed 6 differences in the amino acids encoding between the two parents.
      CONCLUSIONS: Data presented here provide support for Glyma.13 g249400 as a
      possible candidate genes for higher PH in wild soybean line N24852.

PMID- 29587638
TI  - Cerebral microbleeds shouldn't dictate treatment of acute stroke: a retrospective
      cohort study evaluating risk of intracerebral hemorrhage.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) after acute
      ischemic stroke carries the risk of symptomatic intracerebral hemorrhage (sICH).
      Cerebral microbleeds (CMBs) may indicate increased risk of hemorrhage and can be
      seen on magnetic resonance imaging (MRI). In this study, we examined the
      association between CMBs and sICH, focusing on the predictive value of their
      presence, burden, and location. METHODS: Records from all patients presenting to
      two academic stroke centers with acute ischemic stroke treated with IV tPA over a
      5-year period were retrospectively reviewed. Demographic, medical, and imaging
      variables were evaluated. The presence, number, and location (lobar vs nonlobar)
      of CMBs were noted on gradient echo MRI sequences obtained during the admission.
      Univariable and multivariable statistical models were used to determine the
      relationship between CMBs and hemorrhagic (symptomatic and asymptomatic)
      transformation. RESULTS: Of 292 patients (mean age 62.8 years (SD 15.3), 49%
      African-American, 52% women), 21% (n = 62) had at least one CMB, 1% (n = 3) had >
      10 CMBs, and 1% (n = 3) were diagnosed with probable cerebral amyloid angiopathy.
      After treatment, 16% (n = 46) developed hemorrhagic transformation, of which 6
      (2%) were sICH. There was no association between CMB presence (p = .135) or
      location (p = .325) with sICH; however, those with a high CMB burden (> 10 CMB)
      were more likely to develop sICH (OR 37.8; 95% CI: 2.7-539.3; p = .007).
      CONCLUSIONS: Our findings support prior findings that a high CMB burden (> 10) in
      patients with acute stroke treated with IV tPA are associated with a higher risk
      of sICH. However, the overall rate of sICH in the presence of CMB is very low,
      indicating that the presence of CMBs by itself should not dictate the decision to
      treat with thrombolytics.

PMID- 29587639
TI  - MiR-146a G/C rs2910164 variation in South African Indian and Caucasian patients
      with psoriatic arthritis.
AB  - BACKGROUND: Psoriasis and psoriatic arthritis (PsA) are inflammatory associated
      autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating
      inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164),
      aberrantly alters its gene expression and linked with the pathogenesis of several
      disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are
      extremely rare in the indigenous African population and most common in both the
      Indian and Caucasian population. The aim of this study was to investigate whether
      the miR-146a rs2910164 contributes towards psoriasis and PsA development in South
      African Indian and Caucasian patients. METHODS: South African Indian (n = 84) and
      Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects
      (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the
      study. DNA was extracted from whole blood taken from all subjects, and genotyped
      for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from
      pathology reports. The consulting rheumatologist collected all other clinical
      data. RESULTS: Unstratified data (Caucasians + Indians): A significant decrease
      in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at
      inclusion vs. after 6 months of treatment) (18.95 +/- 2.81 mg/L vs. 9.68 +/- 1.32
      mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA
      patients was significantly higher vs. healthy controls (35.78% vs. 26%
      respectively, p = 0.0295, OR = 1.59 95% CI 1.05-2.40). Stratified data (Indians):
      The variant C-allele frequency in Indian PsA patients was significantly higher
      vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13
      3.22). Stratified data (Caucasians): The variant C-allele frequency distribution
      between Caucasian PsA patients and healthy Caucasian controls was similar.
      CONCLUSION: The rs2910164 variant C-allele may play a role in the progression of
      PsA in the South African Indian population. The main limitation in this study was
      the small sample size in the case-control cohorts, with a low overall statistical
      power (post-hoc power analysis = 19%).

PMID- 29587641
TI  - The prevalence of heterozygous F12 mutations in Chinese population and its
      relevance to incidents of thrombosis.
AB  - BACKGROUND: The contribution of moderate coagulation factor XII (FXII) deficiency
      to development of thromboembolism is still undetermined. We have tried to show
      the relevance of FXII deficiency to incidences of venous thrombosis by exploring
      the prevalence of F12 gene mutations in Chinese patients with thrombotic
      disorders. METHODS: One hundred and six patients with venous thromboembolism
      (VTE) and 220 healthy controls were enrolled in study. The coding region and
      flanking sequences of F12 gene were amplified and sequenced to identify genetic
      variances. Patients with F12 mutations were also screened for other thrombotic
      risk factors. RESULTS: Heterozygous F12 gene mutations were identified in 6
      individuals with VTE and 10 healthy controls. Q336X and R66W were found in two
      healthy individuals; D291E was identified in a patient with DVT; and A343P was a
      recurrent mutation with a prevalence of 4.7% (5/106) in patient group and
      3.6%(8/220) in healthy control. The prevalence of heterozygous mutations between
      the two groups had no significant difference. The association of A343P mutations
      with VTE was weak with an OR of 1.31 (95% CI 0.42-4.11). No other thrombophilia
      risk factors screened were positive in patients harboring heterozygous F12
      mutations. CONCLUSIONS: There were conflicting theories about the relationship
      between FXII deficiency and thrombosis formation. Heterozygous F12 mutation
      decreases the plasma FXII activity approximately by half and cause moderate FXII
      deficiency. Although multiple mutations were identified in both groups, the link
      between F12 heterozygous mutation and development of thrombotic disorders is weak
      and further studies are warranted to clarify their relationship.

PMID- 29587640
TI  - Spoligotyping based genetic diversity of Mycobacterium tuberculosis in Ethiopia:
      a systematic review.
AB  - BACKGROUND: Understanding the types of strains and lineages of Mycobacterium
      tuberculosis (M. tuberculosis) circulating in a country is of paramount
      importance for tuberculosis (TB) control program of that country. The main aim of
      this study was to review and compile the results of studies conducted on strains
      and lineages of M. tuberculosis in Ethiopia. METHODS: A systematic search and
      review of articles published on M. tuberculosis strains and lineages in Ethiopia
      were made. PubMed and Google Scholar databases were considered for the search
      while the keywords used were M. tuberculosis, molecular epidemiology, molecular
      typing spoligotyping and Ethiopia. RESULT: Twenty-one studies were considered in
      this review and a total of 3071 M. tuberculosis isolates and 3067 strains were
      included. These studies used spoligotyping and identified five lineages including
      Indo-Ocean, East Asian/Beijing, East African-Indian, Euro-American and Ethiopian
      in a proportion of 7.1%, 0.2%, 23.0%, 64.8%, and 4.1%, respectively. Thus, Euro
      American was the most frequently (64.8%) occurring Lineage while East Asian was
      the least (0.2%) frequently occurring Lineage in the country. Surprisingly, the
      Ethiopian Lineage seemed to be localized to northeastern Ethiopia. In addition,
      the top five clades identified by this review were T, CAS, H, Manu and Ethiopian
      comprising of 48.0%, 23.0%, 11.0%, 6.0% and 4.1% of the strains, respectively.
      Furthermore, predominant shared types (spoligotype patterns) identified were
      SIT149, SIT53, SIT25, SIT37, and SIT21, each consisting of 420, 343, 266, 162 and
      102 isolates, respectively, while, on the other hand, 15% of the strains were
      orphan. CONCLUSION: According to the summary of the results of this review,
      diversified strains and lineages of M. tuberculosis were found in Ethiopia, and
      the frequencies of occurrence of these strains and lineages were variable in
      different regions of the country. This systematic review is registered in the
      PRISMA with the registration number of 42017059263.

PMID- 29587642
TI  - Guillain-Barre syndrome associated with hemorrhagic fever with renal syndrome in
      China: a case report.
AB  - BACKGROUND: We describe a case of Guillain-Barre syndrome (GBS) associated with
      hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS
      associated with Hantavirus infection have been reported so far. CASE
      PRESENTATIONS: A 62-year-old man presented intermittent fever, chill and
      oliguria. According to remarkable leukocytosis, atypical lymphocytes,
      thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was
      suspected as hemorrhagic fever with renal syndromeand certified with positive
      Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all
      extremities. Electromyography showed peripheral nerve injury (mainly in axon).
      The patient was diagnosed as having acute motor sensory axonal neuropathy
      (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and
      was transferred 3 weeks after his first admission to a rehabilitation center.
      CONCLUSIONS: Our case was the 6th reported case of GBS associated with
      hemorrhagic fever with renal syndrome. Moreover, we for the first time classified
      the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS
      should be suspected in patients who are already diagnosed as hemorrhagic fever
      with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent
      now, GBS was only reported in hemorrhagic fever patients in Europe and Asia,
      which termed as hemorrhagic fever with renal syndrome.

PMID- 29587643
TI  - The influence of host genotype and salt stress on the seed endophytic community
      of salt-sensitive and salt-tolerant rice cultivars.
AB  - BACKGROUND: Inherent characteristics and changes in the physiology of rice as it
      attains salt tolerance affect the colonizing bacterial endophytic communities of
      the rice seeds. These transmissible endophytes also serve as a source of the
      plant's microbial community and concurrently respond to the host and
      environmental conditions. This study explores the influence of the rice host as
      well as the impact of soil salinity on the community structure and diversity of
      seed bacterial endophytes of rice with varying tolerance to salt stress.
      Endophytic bacterial diversity was studied through culture-dependent technique
      and Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis. RESULTS:
      Results revealed considerably diverse communities of bacterial endophytes in the
      interior of rice seeds. The overall endophytic bacterial communities of the
      indica rice seeds based on 16S rRNA analysis of clones and isolates are dominated
      by phylum Proteobacteria followed by Actinobacteria and Firmicutes. Community
      profiles show common ribotypes found in all cultivars of the indica subspecies
      representing potential core microbiota belonging to Curtobacterium,
      Flavobacterium, Enterobacter, Xanthomonas, Herbaspirillum, Microbacterium and
      Stenotrophomonas. Clustering analysis shows that the host genotype mainly
      influences the seed endophytic community of the different rice cultivars. Under
      salt stress conditions, endophytic communities of the salt-sensitive and salt
      tolerant rice cultivars shift their dominance to bacterial groups belonging to
      Flavobacterium, Pantoea, Enterobacter, Microbacterium, Kosakonia and
      Curtobacterium. CONCLUSION: The endophytic communities of rice indica seeds are
      shaped by the hosts' genotype, their physiological adaptation to salt stress and
      phylogenetic relatedness. Under salt stress conditions, a few groups of bacterial
      communities become prominent causing a shift in bacterial diversity and
      dominance.

PMID- 29587644
TI  - A novel germline ARMC5 mutation in a patient with bilateral macronodular adrenal
      hyperplasia: a case report.
AB  - BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of
      Cushing's syndrome (CS). BMAH is predominantly believed to be caused by two
      mutations, a germline and somatic one, respectively, as described in the two-hit
      hypothesis. In many familial cases of BMAH, mutations in armadillo repeat
      containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the
      disorder. The objective of this study was to report a case in which the patient
      presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c.
      517C > T, p. Arg173*) alone rather than a two-hit mutation. CASE PRESENTATION: A
      51-year-old woman was identified with masses in the bilateral adrenals. Serum
      cortisol levels were increased significantly both in the morning (08:00 AM) and
      late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal.
      The patient underwent a left adrenalectomy and histopathology substantiated the
      BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline
      ARMC5 mutation (c. 517C > T, p. Arg173*) and in silico analysis predicted that
      the mutation significantly impaired protein function, resulting in inactivated
      ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single
      nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including
      32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS
      related. CONCLUSIONS: A novel germline ARMC5 mutation (c. 517C > T, p. Arg173*)
      was identified that induced BMAH alone without a second mutation. ARMC5
      sequencing may improve the identification of clinical forms of BMAH and allow
      earlier diagnosis of this disease.

PMID- 29587645
TI  - CarrierSeq: a sequence analysis workflow for low-input nanopore sequencing.
AB  - BACKGROUND: Long-read nanopore sequencing technology is of particular
      significance for taxonomic identification at or below the species level. For many
      environmental samples, the total extractable DNA is far below the current input
      requirements of nanopore sequencing, preventing "sample to sequence" metagenomics
      from low-biomass or recalcitrant samples. RESULTS: Here we address this problem
      by employing carrier sequencing, a method to sequence low-input DNA by preparing
      the target DNA with a genomic carrier to achieve ideal library preparation and
      sequencing stoichiometry without amplification. We then use CarrierSeq, a
      sequence analysis workflow to identify the low-input target reads from the
      genomic carrier. We tested CarrierSeq experimentally by sequencing from a
      combination of 0.2 ng Bacillus subtilis ATCC 6633 DNA in a background of 1000 ng
      Enterobacteria phage lambda DNA. After filtering of carrier, low quality, and low
      complexity reads, we detected target reads (B. subtilis), contamination reads,
      and "high quality noise reads" (HQNRs) not mapping to the carrier, target or
      known lab contaminants. These reads appear to be artifacts of the nanopore
      sequencing process as they are associated with specific channels (pores).
      CONCLUSION: By treating sequencing as a Poisson arrival process, we implement a
      statistical test to reject data from channels dominated by HQNRs while retaining
      low-input target reads.

PMID- 29587646
TI  - A hidden Markov tree model for testing multiple hypotheses corresponding to Gene
      Ontology gene sets.
AB  - BACKGROUND: Testing predefined gene categories has become a common practice for
      scientists analyzing high throughput transcriptome data. A systematic way of
      testing gene categories leads to testing hundreds of null hypotheses that
      correspond to nodes in a directed acyclic graph. The relationships among gene
      categories induce logical restrictions among the corresponding null hypotheses.
      An existing fully Bayesian method is powerful but computationally demanding.
      RESULTS: We develop a computationally efficient method based on a hidden Markov
      tree model (HMTM). Our method is several orders of magnitude faster than the
      existing fully Bayesian method. Through simulation and an expression quantitative
      trait loci study, we show that the HMTM method provides more powerful results
      than other existing methods that honor the logical restrictions. CONCLUSIONS: The
      HMTM method provides an individual estimate of posterior probability of being
      differentially expressed for each gene set, which can be useful for result
      interpretation. The R package can be found on https://github.com/k22liang/HMTGO .

PMID- 29587647
TI  - Study of morphological variation of northern Neotropical Ariidae reveals
      conservatism despite macrohabitat transitions.
AB  - BACKGROUND: Morphological convergence triggered by trophic adaptations is a
      common pattern in adaptive radiations. The study of shape variation in an
      evolutionary context is usually restricted to well-studied fish models. We take
      advantage of the recently revised systematics of New World Ariidae and
      investigate skull shape evolution in six genera of northern Neotropical Ariidae.
      They constitute a lineage that diversified in the marine habitat but repeatedly
      adapted to freshwater habitats. 3D geometric morphometrics was applied for the
      first time in catfish skulls and phylogenetically informed statistical analyses
      were performed to test for the impact of habitat on skull diversification after
      habitat transition in this lineage. RESULTS: We found that skull shape is
      conserved throughout phylogeny. A morphospace analysis revealed that freshwater
      and marine species occupy extreme ends of the first principal component axis and
      that they exhibit similar Procrustes variances. Yet freshwater species occupy the
      smallest shape space compared to marine and brackish species (based on partial
      disparity), and marine and freshwater species have the largest Procrustes
      distance to each other. We observed a single case of shape convergence as derived
      from 'C-metrics', which cannot be explained by the occupation of the same
      habitat. CONCLUSIONS: Although Ariidae occupy such a broad spectrum of different
      habitats from sea to freshwater, the morphospace analysis and analyses of shape
      and co-variation with habitat in a phylogenetic context shows that conservatism
      dominates skull shape evolution among ariid genera.

PMID- 29587648
TI  - Identification of cold stress responsive microRNAs in two winter turnip rape
      (Brassica rapa L.) by high throughput sequencing.
AB  - BACKGROUND: Low temperature is a major abiotic stress affecting the production of
      rapeseed in China by impeding plant growth and development. A comprehensive
      knowledge of small-RNA expression pattern in Brassica rapa under cold stress
      could improve our knowledge of microRNA-mediated stress responses. RESULTS: A
      total of 353 cold-responsive miRNAs, 84 putative novel and 269 conserved miRNAs,
      were identified from the leaves and roots of two winter turnip rape varieties
      'Longyou 7' (cold-tolerant) and 'Tianyou 4' (cold-sensitive), which were stressed
      under - 4  degrees C for 8 h. Eight conserved (miR166h-3p-1, miR398b-3p, miR398b
      3p-1, miR408d, miR156a-5p, miR396h, miR845a-1, miR166u) and two novel miRNAs (Bra
      novel-miR3153-5p and Bra-novel-miR3172-5p) were differentially expressed in
      leaves of 'Longyou 7' under cold stress. Bra-novel-miR3936-5p was up-regulated in
      roots of 'Longyou 7' under cold stress. Four and five conserved miRNAs were
      differentially expressed in leaves and roots of 'Tianyou 4' after cold stress.
      Besides, we found two conserved miRNAs (miR319e and miR166m-2) were down
      regulated in non-stressed roots of 'Longyou 7' compared with 'Tianyou 4'. After
      cold stress, we found two and eight miRNAs were differentially expressed in
      leaves and roots of 'Longyou 7' compared with 'Tianyou 4'. The differentially
      expressed miRNAs between two cultivars under cold stress include novel miRNAs and
      the members of the miR166 and miR319 families. A total of 211 target genes for 15
      known miRNAs and two novel miRNAs were predicted by bioinformatic analysis,
      mainly involved in metabolic processes and stress responses. Five differentially
      expressed miRNAs and predicted target genes were confirmed by quantitative
      reverse transcription PCR, and the expressional changes of target genes were
      negatively correlated to differentially expressed miRNAs. Our data indicated that
      some candidate miRNAs (e.g., miR166e, miR319, and Bra-novel-miR3936-5p) may play
      important roles in plant response to cold stress. CONCLUSIONS: Our work indicates
      that miRNA and putative target genes mediated metabolic processes and stress
      responses are significant to cold tolerance in B. rapa.

PMID- 29587649
TI  - Factors associated with human West Nile virus infection in Ontario: a generalized
      linear mixed modelling approach.
AB  - BACKGROUND: West Nile Virus (WNV) is a mosquito-borne pathogen that has become
      established in North America. Risk for human infection varies geographically in
      accordance with climate and population factors. Though often asymptomatic, human
      WNV infection can cause febrile illness or, rarely, neurologic disease. WNV has
      become a public health concern in Canada since its introduction in 2001. METHODS:
      To identify predictors of human WNV incidence at the public health unit (PHU)
      level in Ontario, Canada, we combined data on environmental and population
      characteristics of PHUs with historical mosquito and human surveillance records
      from 2002 to 2013. We examined the associations between annual WNV incidence and
      monthly climate indices (e.g. minimum and maximum temperature, average
      precipitation), land cover (e.g. deciduous forest, water), population structure
      (e.g. age and sex composition) and the annual percentage of WNV-positive mosquito
      pools from 2002 to 2013. We then developed a generalized linear mixed model with
      a Poisson distribution adjusting for spatial autocorrelation and repeat measures.
      Further to this, to examine potential 'early season' predictors of WNV incidence
      in a given year, we developed a model based on winter and spring monthly climate
      indices. RESULTS: Several climate indices, including mean minimum temperature (o
      C) in February (RR = 1.58, CI: [1.42, 1.75]), and the annual percentage of WNV
      positive mosquito pools (RR = 1.07, CI: [1.04, 1.11]) were significantly
      associated with human WNV incidence at the PHU level. Higher winter minimum
      temperatures were also strongly associated with annual WNV incidence in the
      'early season' model (e.g. February minimum temperature (RR = 1.91, CI: [1.73,
      2.12]). CONCLUSIONS: Our study demonstrates that early season temperature and
      precipitation indices, in addition to the percentage of WNV-positive mosquito
      pools in a given area, may assist in predicting the likelihood of a more severe
      human WNV season in southern regions of Ontario, where WNV epidemics occur
      sporadically.

PMID- 29587650
TI  - Biopsy-proven vancomycin-induced acute kidney injury: a case report and
      literature review.
AB  - BACKGROUND: Vancomycin is the first-line antibiotic for methicillin-resistant
      Staphylococcus aureus and coagulase-negative strains. The risk of vancomycin
      induced acute kidney injury increases with plasma vancomycin levels. Vancomycin
      induced acute kidney injury is histologically characterized by acute interstitial
      nephritis and/or acute tubular necrosis. However, only 12 biopsy-proven cases of
      vancomycin-induced acute kidney injury have been reported so far, as renal biopsy
      is rarely performed for such cases. Current recommendations for the prevention or
      treatment of vancomycin-induced acute kidney injury are drug monitoring of plasma
      vancomycin levels using trough level and drug withdrawal. Oral prednisone and
      high-flux haemodialysis have led to the successful recovery of renal function in
      some biopsy-proven cases. CASE PRESENTATION: We present the case of a 41-year-old
      man with type 1 diabetes mellitus, who developed vancomycin-induced acute kidney
      injury during treatment for Fournier gangrene. His serum creatinine level
      increased to 1020.1 MUmol/L from a baseline of 79.6 MUmol/L, and his plasma
      trough level of vancomycin peaked at 80.48 MUg/mL. Vancomycin discontinuation and
      frequent haemodialysis with high-flux membrane were immediately performed
      following diagnosis. Renal biopsy showed acute tubular necrosis and focal acute
      interstitial nephritis, mainly in the medullary rays (medullary ray injury).
      There was no sign of glomerulonephritis, but mild diabetic changes were detected.
      He was discharged without continuing haemodialysis (serum creatinine level, 145.0
      MUmol/L) 49 days after initial vancomycin administration. CONCLUSIONS: This case
      suggests that frequent haemodialysis and renal biopsy could be useful for the
      treatment and assessment of vancomycin-induced acute kidney injury, particularly
      in high-risk cases or patients with other renal disorders.

PMID- 29587651
TI  - Pretreatment loss to follow-up of tuberculosis patients in Chennai, India: a
      cohort study with implications for health systems strengthening.
AB  - BACKGROUND: Pretreatment loss to follow-up (PTLFU) is a barrier to tuberculosis
      (TB) control in India's Revised National TB Control Programme (RNTCP). PTLFU
      studies have not been conducted in India's mega-cities, where patient mobility
      may complicate linkage to care. METHODS: We collected data from patient
      registries for May 2015 from 22 RNTCP designated microscopy centers (DMCs) in
      Chennai and audited addresses and phone numbers for patients evaluated for
      suspected TB to understand how missing contact information may contribute to
      PTLFU. From November 2015 to June 2016, we audited one month of records from each
      of these 22 DMCs and tracked newly diagnosed smear-positive patients using RNTCP
      records, phone calls, and home visits. We defined PTLFU cases as including: (1)
      patients who did not start TB therapy within 14 days and (2) patients who started
      TB therapy but were lost to follow-up or died before official RNTCP registration.
      We used multivariate logistic regression to identify factors associated with
      PTLFU. RESULTS: In the audit of May 2015 DMC registries, out of 3696 patients
      evaluated for TB, 1273 (34.4%) had addresses and phone numbers that were
      illegible or missing. Out of 344 smear-positive patients tracked from November
      2015 to June 2016, 40 (11.6%) did not start TB therapy within 14 days and 36
      (10.5%) started therapy but were lost to follow-up or died before official RNTCP
      registration, for an overall PTLFU rate of 22.1% (95%CI: 17.8%-26.4%). Of all
      PTLFU patients, 55 (72.4%) were lost to follow-up and 21 (27.6%) died before
      starting treatment or before RNTCP registration. In the regression analysis, age
      > 50 years (OR 2.9, 95%CI 1.4-6.5), history of prior TB (OR 3.9, 95%CI 2.2-7.1),
      evaluation at a high patient volume DMC (OR 3.2, 95% CI 1.7-6.3), and absence of
      legible patient contact information (OR 4.5, 95%CI 1.3-15.1) were significantly
      associated with PTLFU. CONCLUSIONS: In an Indian mega-city, we found a high PTLFU
      rate, especially in patients with a prior TB history, who are at greater risk for
      having drug-resistance. Enhancing quality of care and health system transparency
      is critical for improving linkage of newly diagnosed patients to TB care in urban
      India.

PMID- 29587652
TI  - Quantitative profiling of BATF family proteins/JUNB/IRF hetero-trimers using Spec
      seq.
AB  - BACKGROUND: BATF family transcription factors (BATF, BATF2 and BATF3) form hetero
      trimers with JUNB and either IRF4 or IRF8 to regulate cell fate in T cells and
      dendritic cells in vivo. While each combination of the hetero-trimer has a
      distinct role, some degree of cross-compensation was observed. The basis for the
      differential actions of IRF4 and IRF8 with BATF factors and JUNB is still
      unknown. We propose that the differences in function between these hetero-trimers
      may be caused by differences in their DNA binding preferences. While all three
      BATF family transcription factors have similar binding preferences when binding
      as a hetero-dimer with JUNB, the cooperative binding of IRF4 or IRF8 to the
      hetero-dimer/DNA complex could change the preferences. We used Spec-seq, which
      allows for the efficient and accurate determination of relative affinity to a
      large collection of sequences in parallel, to find differences between
      cooperative DNA binding of IRF4, IRF8 and BATF family members. RESULTS: We found
      that without IRF binding, all three hetero-dimer pairs exhibit nearly the same
      binding preferences to both expected wildtype binding sites TRE (TGA(C/G)TCA) and
      CRE (TGACGTCA). IRF4 and IRF8 show the very similar DNA binding preferences when
      binding with any of the three hetero-dimers. No major change of binding
      preferences was found in the half-sites between different hetero-trimers. IRF
      proteins bind with substantially lower affinity with either a single nucleotide
      spacer between IRF and BATF binding site or with an alternative mode of binding
      in the opposite orientation. In addition, the preference to CRE binding site was
      reduced with either IRF binding in all BATF-JUNB combinations. CONCLUSIONS: The
      specificities of BATF, BATF2 and BATF3 are all very similar as are their
      interactions with IRF4 and IRF8. IRF proteins binding adjacent to BATF sites
      increases affinity substantially compared to sequences with spacings between the
      sites, indicating cooperative binding through protein-protein interactions. The
      preference for the type of BATF binding site, TRE or CRE, is also altered when
      IRF proteins bind. These in vitro preferences aid in the understanding of in vivo
      binding activities.

PMID- 29587653
TI  - Efficient anchoring of alien chromosome segments introgressed into bread wheat by
      new Leymus racemosus genome-based markers.
AB  - BACKGROUND: The tertiary gene pool of bread wheat, to which Leymus racemosus
      belongs, has remained underutilized due to the current limited genomic resources
      of the species that constitute it. Continuous enrichment of public databases with
      useful information regarding these species is, therefore, needed to provide
      insights on their genome structures and aid successful utilization of their genes
      to develop improved wheat cultivars for effective management of environmental
      stresses. RESULTS: We generated de novo DNA and mRNA sequence information of L.
      racemosus and developed 110 polymorphic PCR-based markers from the data, and to
      complement the PCR markers, DArT-seq genotyping was applied to develop additional
      9990 SNP markers. Approximately 52% of all the markers enabled us to clearly
      genotype 22 wheat-L. racemosus chromosome introgression lines, and L. racemosus
      chromosome-specific markers were highly efficient in detailed characterization of
      the translocation and recombination lines analyzed. A further analysis revealed
      remarkable transferability of the PCR markers to three other important Triticeae
      perennial species: L. mollis, Psathyrostachys huashanica and Elymus ciliaris,
      indicating their suitability for characterizing wheat-alien chromosome
      introgressions carrying chromosomes of these genomes. CONCLUSION: The efficiency
      of the markers in characterizing wheat-L. racemosus chromosome introgression
      lines proves their reliability, and their high transferability further broadens
      their scope of application. This is the first report on sequencing and
      development of markers from L. racemosus genome and the application of DArT-seq
      to develop markers from a perennial wild relative of wheat, marking a paradigm
      shift from the seeming concentration of the technology on cultivated species.
      Integration of these markers with appropriate cytogenetic methods would
      accelerate development and characterization of wheat-alien chromosome
      introgression lines.

PMID- 29587654
TI  - Antepartum urinary tract infection and postpartum depression in Taiwan - a
      nationwide population-based study.
AB  - BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial
      infections in pregnant women due to anatomic and physiologic changes in the
      female urinary tract during pregnancy, and antepartum UTIs can cause adverse
      pregnancy outcomes that may induce mental stress. There have only been a few
      studies, however, investigating antepartum UTIs and mental stress. As such, the
      present study was conducted in order to investigate the association between
      antepartum UTIs and postpartum depression (PPD). METHODS: We used data from the
      2000-2013 National Health Insurance Research Database (NHIRD) of Taiwan. Data
      regarding a total of 55,087 singleton pregnancies was utilized, including data
      regarding 406 women who were newly diagnosed with PPD in the first 6 months
      postpartum. The associations between PPD and antepartum UTIs or other risk
      factors were examined by multiple logistic regression analysis. RESULTS: The
      logistic regression analysis results indicated that PPD was associated with
      antepartum UTIs (adjusted odds ratio [aOR] 1.27; 95% confidence interval [CI]
      (1.07-1.65). Furthermore, the risk of PPD was higher in women with an upper
      antepartum UTI (aOR 2.97 (1.31, 6.77) than in those with a lower antepartum UTI
      (aOR 1.21 (1.02, 1.58)). CONCLUSIONS: Antepartum UTIs, particularly upper
      antepartum UTIs, are significantly associated with PPD. This information may
      encourage physicians to pay greater attention to the mental health of women who
      have suffered upper UTIs during their pregnancies.

PMID- 29587655
TI  - Impedance cardiography as tool for continuous hemodynamic monitoring during
      cesarean section: randomized, prospective double blind study.
AB  - BACKGROUND: Impedance Cardiography (ICG) is a non-invasive tool for continuous
      hemodynamic monitoring. Aims of our study were to assess the utility of ICG to
      evaluate the hemodynamic impact of 6 mg (GL6) vs 8 mg (GL8) levobupivacaine
      combined with fentanyl in healthy patients undergoing elective cesarean section;
      secondary, to compare the duration and quality of analgesia and anesthesia.
      METHODS: Sixty-two women receiving combined spinal-epidural (CSE) for elective
      cesarean delivery were randomly allocated to GL6 or GL8 groups. Mean arterial
      pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI),
      heart rate (HR), stroke volume index (SVI) were recorded from Tbaseline to 31 min
      after CSE by ICG. Sensory and motor blocks, patients and surgeons satisfaction,
      neonatal data were also recorded. RESULTS: Fifteen of 32 patients in GL6 and 15
      of 30 patients in GL8 experienced hypotension at T2 vs Tbaseline (P < .001) and
      SVRI reduction (P = .035 and P < .001 respectively). MAP, CI and SVRI were always
      slightly higher in GL6 vs GL8. HR and SVI remained stable until the end of
      surgery in all patients. Total ephedrine requirements was higher in GL8 (P =
      .010). The onset and offset time of sensory and motor block were similar in both
      groups, but the number of patients with motor block was lower in GL6 vs GL8 (P =
      .001). Patients and surgeon satisfaction scores, the number of patients needed
      systemic rescue doses, neonatal data were similar in both groups. CONCLUSIONS:
      ICG is a useful noninvasive tool to monitor continuously hemodynamics during
      cesarean section. The hemodynamic stability, the satisfying sensory block and
      rapid mobilization provided by low levobupivacaine dose may be particularly
      advantageous in obstetric patients. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT03170427 . Retrospectively Registered (Date of registration: May 2017).

PMID- 29587656
TI  - Erlotinib treatment after platinum-based therapy in elderly patients with non
      small-cell lung cancer in routine clinical practice - results from the ElderTac
      study.
AB  - BACKGROUND: In this prospective non-interventional study, the effectiveness and
      tolerability of erlotinib in elderly patients with non-small-cell lung cancer
      (NSCLC) after >=1 platinum-based chemotherapy were assessed. METHODS: A total of
      385 patients >=65 years of age with advanced NSCLC receiving erlotinib were
      observed over 12 months. The primary endpoint was the 1-year overall survival
      (OS) rate. RESULTS: Patients were predominantly Caucasian (99.2%), a mean of 73
      years old; 24.7% had an Eastern Cooperative Oncology Group performance status
      (ECOG PS) >=2. Most common tumor histologies were adenocarcinoma (64.9%) and
      squamous cell carcinoma (22.3%). Of 119 patients tested, 15.1% had an activating
      epidermal growth factor receptor gene (EGFR) mutation. The 1-year OS rate was 31%
      (95% CI 25-36) with a median OS of 7.1 months (95% CI 6.0-7.9). OS was
      significantly better in females than males (p = 0.0258) and in patients with an
      EGFR mutation compared to EGFR wild-type patients (p = 0.0004). OS was not
      affected by age (p = 0.3436) and ECOG PS (p = 0.5364). Patients with squamous
      NSCLC tended to live longer than patients with non-squamous EGFR wild-type tumors
      (median OS: 8.6 vs 5.5 months). Cough and dyspnea improved during the observation
      period. The erlotinib safety profile was comparable to that in previous studies
      with rash (45.2%) and diarrhea (22.6%) being the most frequently reported adverse
      events. CONCLUSIONS: Erlotinib represents a suitable palliative treatment option
      in further therapy lines for elderly patients with advanced NSCLC. The results
      obtained under real-life conditions add to our understanding of the benefits and
      risks of erlotinib in routine clinical practice. TRIAL REGISTRATION: BfArM (
      https://www.bfarm.de ; ML23023); ClinicalTrials.gov (NCT01535729; 20 Feb 2012).

PMID- 29587657
TI  - Effective treatment of apatinib in desmoplastic small round cell tumor: a case
      report and literature review.
AB  - BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant
      sarcoma with poor prognosis due to lack of effective treatments. Apatinib is a
      new potent oral small-molecule tyrosine kinase inhibitor, and targets the
      intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2).
      In this study, we presented a case of intra-abdominal DSRCT which was effectively
      treated by apatinib. CASE PRESENTATION: A 32-year-old man was admitted due to
      increasing urination frequency and palpable mass in right lower abdomen for 2
      months. The mass was resected and diagnosed DSRCT. The patient refused
      chemotherapy and radiotherapy,and used Chinese medicine only. Six months after
      the surgery, the patient re-hospitalized due to growing abdominal mass and
      ascites. Intraperitoneal cisplatin treatment showed little effect. Apatinib was
      then recommended. Apatinib revealed outstanding effect on reducing mass size and
      ascites during 2-month treatment. Apatinib therapy continued for additional 2
      months, and the patient was in good condition. The only toxicity was hand-food
      syndrome, which was controllable and well tolerated. CONCLUSION: It is the first
      report that apatinib is effective on DSRCT. This report may provide an additional
      option for the treatment of metastatic DSRCT.

PMID- 29587658
TI  - De-medicalization of birth by reducing the use of oxytocin for augmentation among
      first-time mothers - a prospective intervention study.
AB  - BACKGROUND: The use of synthetic oxytocin for augmentation of labor is rapidly
      increasing worldwide. Hyper-stimulation is the most significant side effect,
      which may cause fetal distress and operative delivery. We performed an
      intervention consisting of an educational program and modified guidelines to
      achieve a more appropriate use of oxytocin. METHODS: This prospective
      intervention study included 431 first-time mothers at term with spontaneous onset
      of labor before (October 2012 to May 2013), and 664 after the intervention (April
      2014 to April 2015). Our outcomes were prevalence and duration of oxytocin
      treatment, mode of delivery, indication for operative delivery, episiotomy, anal
      sphincter tears, bleeding, labor duration, pain relief and the effect of oxytocin
      on mode of delivery. RESULTS: After the intervention, 52.9% were diagnosed with
      dystocia, compared with 68.9% before (p < 0.001). Oxytocin was not always used in
      accordance with the guidelines, but a significant reduction in oxytocin rates
      from 63.3% to 54.1% (p < 0.001) was obtained. More women without dystocia
      according to the existing guidelines were augmented after the intervention (18.9%
      vs 8.4%, p < 0.001). Assessing all labors, the median duration of oxytocin
      treatment was reduced by 72% (from 90 to 25 min) without increasing the median
      duration of labor (385 min in both groups). There was a moderate reduction in
      operative vaginal deliveries from 26.9 to 21.5% (p = 0.04), and dystocia as an
      indication for these deliveries increased (p = 0.01). There was a moderate
      increase in caesarean sections from 6.7 to 10.2% (p = 0.05), but no increase in
      dystocia as an indication for these deliveries. Women receiving oxytocin were
      more likely to have an operative vaginal birth, even after adjusting for birth
      weight, epidural analgesia and labor duration, OR: 2.1 (CI 1.1-4.0) before and OR
      2.7 (CI 1.6-4.5) after the intervention. CONCLUSIONS: Our intervention led to a
      significant reduction in the use of oxytocin. However, more than half of the
      women remained diagnosed with dystocia. Operative vaginal births seem to be
      associated with oxytocin treatment. Therefore, augmentation with oxytocin should
      be used with caution and only when medically indicated. Even more modified
      guidelines for augmentation than the ones applied in this study might be
      appropriate.

PMID- 29587659
TI  - Detection of circulating tumor cells in patients with pituitary tumors.
AB  - BACKGROUND: Circulating tumor cells (CTCs) are tumor cells that have shed from a
      primary tumor and circulate in the peripheral blood. Recent experimental and
      clinical studies show that CTCs can be detected in early-stage disease. CASE
      PRESENTATION: We report three cases of pituitary adenoma (PA) in which tumor
      cells with particles were detected in the interstitial vascular compartment by
      transmission electron microscopy. Tumors were completely resected.
      Immunohistochemical analysis showed a beta-catenin score of 10.5 +/- 1.5 in the
      three cases with CTCs compared with 2.4 +/- 0.5 in 24 control adenomas. The Ki-67
      labeling index was 2.1 +/- 0.7 in CTCs vs. 0.2 +/- 0.3 in control cases (p =
      0.043), and the p53 score was 4.33 +/- 1.3 vs. 0.31 +/- 0.17 (p = 0.000). The E
      cadherin score did not differ significantly between the two groups. CONCLUSIONS:
      CTCs can be detected in benign tumors such as PAs and not only in late-stage
      malignant tumors with apparent distant metastases. The present findings suggest
      that pituitary carcinomas develop from adenomas.

PMID- 29587660
TI  - Patterns of follow up and survivorship care for people with colorectal cancer in
      new South Wales, Australia: a population-based survey.
AB  - BACKGROUND: The incidence and survival rates for colorectal cancer in Australia
      are among the highest in the world. With population growth and ageing there are
      increasing numbers of colorectal cancer survivors in the community, yet little is
      known of their ongoing follow up and survivorship care experiences. This study
      investigated patterns and predictors of follow up and survivorship care received
      and recommended for adults with colorectal cancer in New South Wales (NSW),
      Australia. METHODS: Cross-sectional analysis within the NSW Bowel Cancer Care
      Survey, a population-based cohort of adults diagnosed with colorectal cancer
      between April 2012 and May 2013 in NSW. One year after diagnosis, participants
      completed a study specific questionnaire about their follow up and survivorship
      care experience and plans. Logistic regression was used to identify independent
      predictors of guideline-recommended care. RESULTS: Of 1007 eligible people, 560
      (56%) participated in the NSW Bowel Cancer Care Survey with 483 (86% of study
      participants, 48% of invited sample) completing the survivorship survey. Among
      these 483 participants, only 110 (23%, 95% Confidence Interval CI 19-27%) had
      received a written follow up plan, with this more common among migrants, non
      urban dwellers and those with little experience of the health system. Of 379
      (78%) people treated with curative intent, most were receiving ongoing colorectal
      cancer follow up from multiple providers with 28% (23-32%) attending three or
      more different doctors. However, less than half had received guideline
      recommended follow-up colonoscopy (46%, CI 41-51%) or carcino-embryonic antigen
      assay (35%, CI 30-40%). Socio-economic advantage was associated with receipt of
      guideline-recommended care. While participants reported high interest in
      improving general health and lifestyle since their cancer diagnosis, few had
      received advice about screening for other cancers (24%, CI 19-28%) or assistance
      with lifestyle modification (30%, CI 26-34%). Less than half (47%, CI 43-52%) had
      discussed their family's risk of cancer with a doctor since their diagnosis.
      CONCLUSIONS: Survivorship care was highly variable, with evident socioeconomic
      disparities and missed opportunities for health promotion.

PMID- 29587661
TI  - Characteristics and outcome of the COEUR Canadian validation cohort for ovarian
      cancer biomarkers.
AB  - BACKGROUND: Ovarian carcinoma is the most lethal gynecological malignancy due to
      early dissemination and acquired resistance to platinum-based chemotherapy.
      Reliable markers that are independent and complementary to clinical parameters
      are needed to improve the management of patients with this disease. The Canadian
      Ovarian Experimental Unified Resource (COEUR) provides researchers with
      biological material and associated clinical data to conduct biomarker validation
      studies. Using standards defined by the Canadian Tissue Repository Network
      (CTRNet), we have previously demonstrated the quality of the biological material
      from this resource. Here we describe the clinical characteristics of the COEUR
      cohort. METHODS: With support from 12 Canadian ovarian cancer biobanks in Canada,
      we created a central retrospective cohort comprised of more than 2000 patient
      tissue samples with associated clinical data, including 1246 high-grade serous,
      102 low-grade serous, 295 endometrioid, 259 clear cell and 89 mucinous carcinoma
      histotypes. A two-step reclassification process was applied to assure
      contemporary histological classification (histotyping). For each histotypes
      individually, we evaluated the association between the known clinico-pathological
      parameters (stage, cytoreduction, chemotherapy treatment, BRCA1 and BRCA2
      mutation) and patient outcome by using Kaplan-Meier and Cox proportional hazard
      regression analyses. RESULTS: The median follow-up time of the cohort was 45
      months and the 5-year survival rate for patients with high-grade serous
      carcinomas was 34%, in contrast to endometrioid carcinomas with 80% at 5 years.
      Survival profiles differed by histotype when stratified by stage or
      cytoreduction. Women with mucinous or clear cell carcinomas at advanced stage or
      with non-optimally debulked disease had the worst outcomes. In high-grade serous
      carcinoma, we observed significant association with longer survival in women
      harboring BRCA1 or BRCA2 mutation as compared to patients without detectable
      mutation. CONCLUSIONS: Our results show the expected survival rates, as compared
      with current literature, in each histotype suggesting that the cohort is an
      unbiased representation of the five major histotypes. COEUR, a one stop
      comprehensive biorepository, has collected mature outcome data and relevant
      clinical data in a comprehensive manner allowing stratified analysis.

PMID- 29587662
TI  - Randomized clinical trial testing the efficacy and safety of 0.5% colchicine
      cream versus photodynamic therapy with methyl aminolevulinate in the treatment of
      skin field cancerization: study protocol.
AB  - BACKGROUND: The primary clinical manifestation of skin field cancerization is the
      presence of actinic keratoses (AKs). Current treatments for AKs related to skin
      field cancerization include photodynamic therapy (PDT) and colchicine. The
      objective of this study is to evaluate the efficacy and safety of 0.5% colchicine
      cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin
      field cancerization. METHODS: In a randomized controlled and open clinical trial
      with a blind histopathological and immunohistochemical analysis, 36 patients with
      up to 10 AKs on their forearms will be included from the outpatient clinic. The
      forearms will be randomized into two groups, clinically evaluated and biopsied
      for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be
      treated with 0.5% colchicine cream for 10 days, and the other forearm will
      receive one session of MAL-PDT; the forearms will subsequently be reassessed
      clinically and histologically after 60 days (T60) of treatment. The primary
      endpoint will be the point of complete clearance of AKs in T60. The sample size
      will enable a detection in the reduction of over 10% in AK counts between the
      groups with power of 0.9 and an alpha of 0.05, accounting for an estimated
      dropout rate of 10%, resulting in 36 patients (72 forearms). All participants
      included in the randomized study will be part of the analysis, and the final
      outcomes of any dropouts will be the value of their last visit (LOCF). The
      statistical analysis will be performed using SPSS 22.0, and a p value < 5% will
      be considered to be significant. DISCUSSION: It is expected that colchicine will
      be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and
      there will be good tolerability in both groups. Colchicine intervention is novel
      in that it provides a new alternative to MAL-PDT. Moreover, this drug is
      inexpensive that may be a potential treatment of skin field cancerization that
      can be prescribed in public health systems with good results. TRIAL REGISTRATION:
      The trial is registered in Brazilian Registry for Clinical Trials (Registration
      number: RBR-8y3sj9 , date assigned May 4, 2016, retrospectively registered).

PMID- 29587663
TI  - Development of primary human pancreatic cancer organoids, matched stromal and
      immune cells and 3D tumor microenvironment models.
AB  - BACKGROUND: Patient-derived tumor models are the new standard for pre-clinical
      drug testing and biomarker discovery. However, the emerging technology of primary
      pancreatic cancer organoids has not yet been broadly implemented in research, and
      complex organotypic models using organoids in co-culture with stromal and immune
      cellular components of the tumor have yet to be established. In this study, our
      objective was to develop and characterize pancreatic cancer organoids and multi
      cell type organotypic co-culture models to demonstrate their applicability to the
      study of pancreatic cancer. METHODS: We employed organoid culture methods and
      flow cytometric, cytologic, immunofluorescent and immunohistochemical methods to
      develop and characterize patient-derived pancreatic cancer organoids and multi
      cell type organotypic co-culture models of the tumor microenvironment. RESULTS:
      We describe the culture and characterization of human pancreatic cancer organoids
      from resection, ascites and rapid autopsy sources and the derivation of adherent
      tumor cell monocultures and tumor-associated fibroblasts from these sources.
      Primary human organoids displayed tumor-like cellular morphology, tissue
      architecture and polarity in contrast to cell line spheroids, which formed
      homogenous, non-lumen forming spheres. Importantly, we demonstrate the
      construction of complex organotypic models of tumor, stromal and immune
      components of the tumor microenvironment. Activation of myofibroblast-like cancer
      associated fibroblasts and tumor-dependent lymphocyte infiltration were observed
      in these models. CONCLUSIONS: These studies provide the first report of novel and
      disease-relevant 3D in-vitro models representing pancreatic tumor, stromal and
      immune components using primary organoid co-cultures representative of the tumor
      microenvironment. These models promise to facilitate the study of tumor-stroma
      and tumor-immune interaction and may be valuable for the assessment of
      immunotherapeutics such as checkpoint inhibitors in the context of T-cell
      infiltration.

PMID- 29587664
TI  - Management and obstetric outcomes of 17 heterotopic interstitial pregnancies.
AB  - BACKGROUND: Heterotopic interstitial pregnancy is a rare variant of heterotopic
      pregnancies, and it poses challenges in treating the heterotopic pregnancy and
      preserving the intrauterine pregnancy. However, there is no clear consensus
      regarding the optimal management. The aim of this study was to investigate the
      pregnancy outcomes of women diagnosed with heterotopic interstitial pregnancy.
      METHODS: A total of 17 women diagnosed with heterotopic interstitial pregnancy
      between July 2010 and December 2015 were included. General characteristics of
      each patient, including age, gravidity and parity, history of pelvic inflammatory
      disease or surgery, and especially the corresponding therapeutic interventions,
      were retrospectively analyzed. Moreover, pregnancy outcomes were further followed
      by face-to-face interview. RESULTS: Of the 17 patients, 10 (58.5%) underwent
      surgical treatment (7 laparoscopic cornual resection, and 3 laparotomy); and 3
      cases simultaneously terminated the intrauterine pregnancy by suction evacuation.
      Compared with laparotomy, laparoscopic cornual section showed shorter operative
      time (median 40 vs. 70 min), less blood loss (150 vs. 400 ml) and shorter
      hospital stay (2 vs. 4 days). In addition, 4 (23.5%) patients underwent selective
      embryo reduction under transvaginal ultrasound guidance. Expectant management was
      chosen in the remaining 3 patients. In the follow-up study, other than a case of
      missed miscarriage, the other 13 women who remained committed to their
      pregnancies all delivered healthy babies either by caesarean section or vaginal
      birth. No congenital anomalies were reported, and all the infants were in good
      growth and development. CONCLUSIONS: Laparoscopic cornual resection is a feasible
      approach with favorable surgical and long-term pregnancy outcomes. Additionally,
      medical or expectant management may be a viable treatment option for selected
      symptom-free patient. Although the survival of the intrauterine pregnancy could
      not always be assured, the prognosis for a woman with heterotopic interstitial
      pregnancy is generally good.

PMID- 29587665
TI  - Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus
      concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally
      advanced nasopharyngeal carcinoma.
AB  - BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT
      AC) is currently recommended as the standard treatment for locally advanced
      nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by
      concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing
      tumor size and controlling micrometastases before main treatment. The aim of this
      study was to investigate and compare survival outcomes between LA-NPC patients
      treated with CCRT-AC and those treated with NAC-CCRT. METHODS: This retrospective
      cohort study included consecutive histologically confirmed LA-NPC patients that
      were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010
      to October 2014 study period. CCRT in both protocols consisted of 3-week cycles
      of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted
      of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4
      for a maximum three cycles. The primary endpoint was 5-year overall survival
      (OS). Flexible parametric survival analysis was used, because the proportional
      hazards assumption of Cox regression was violated. RESULTS: Of the 266 LA-NPC
      patients that received treatment during the study period, 79 received NAC-CCRT
      and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more
      patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in
      NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3
      year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p =
      0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84%
      and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95%
      confidence interval (CI): 0.45-1.56; p = 0.571). Also, adjusted analysis of
      distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p =
      0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival
      revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI:
      0.98-4.87; p = 0.057). CONCLUSIONS: The results suggested that prognosis in the
      NAC-CCRT treated patients was not superior to that of the CCRT-AC treated
      individuals. In patients that receive neoadjuvant chemotherapy, locoregional
      relapse should be of concern. High-risk distant metastasis patients (N3 stage)
      that could achieve survival advantage from NAC-CCRT is an interesting and
      important topic for further study.

PMID- 29587666
TI  - Cost effectiveness analysis of afatinib versus pemetrexed-cisplatin for first
      line treatment of locally advanced or metastatic EGFR mutation positive non-small
      cell lung cancer from the Singapore healthcare payer's perspective.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung
      cancers and is associated with a poor prognosis. Afatinib is an irreversible ErbB
      family blocker recommended in clinical guidelines as a first-line treatment for
      NSCLC which harbours an epidermal growth factor receptor (EGFR) mutation. The
      objective of this study was to evaluate the cost-effectiveness of afatinib versus
      pemetrexed-cisplatin for first-line treatment of locally advanced or metastatic
      EGFR mutation positive NSCLC in Singapore. METHODS: A partitioned survival model
      with three health states (progression-free, progressive disease and death) was
      developed from a healthcare payer perspective. Survival curves from the LUX-Lung
      3 trial (afatinib versus pemetrexed-cisplatin chemotherapy) were extrapolated
      beyond the trial period to estimate the underlying progression-free survival and
      overall survival parametric distributions. Rates of adverse reactions were also
      estimated from LUX-Lung 3 while health utilities from overseas were derived from
      the literature in the absence of local estimates. Direct costs were sourced from
      public healthcare institutions in Singapore. Incremental cost-effectiveness
      ratios (ICERs) were calculated over a 5 year time horizon. Deterministic and
      probabilistic sensitivity analyses and additional scenario analyses were
      conducted to explore the impact of uncertainties and assumptions on the cost
      effectiveness results. RESULTS: In the base-case analysis, the ICER for afatinib
      versus pemetrexed-cisplatin was SG$137,648 per quality-adjusted life year (QALY)
      gained and SG$109,172 per life-year gained. One-way sensitivity analysis showed
      the ICER was most sensitive to variations in the utility values, the cost of
      afatinib and time horizon. Scenario analyses showed that even reducing the cost
      of afatinib by 50% led to a high ICER which was unlikely to represent a cost
      effective use of healthcare resources. CONCLUSIONS: Compared with pemetrexed
      cisplatin, afatinib is not cost-effective as a first-line treatment for advanced
      EGFR mutation-positive NSCLC in Singapore. The findings from our study will be
      useful to inform local healthcare decision-making and resource allocations for
      NSCLC treatments, together with other considerations such as clinical
      effectiveness, safety and affordability of TKIs.

PMID- 29587667
TI  - Outcomes of Pemetrexed-based chemotherapies in HER2-mutant lung cancers.
AB  - BACKGROUND: HER2 mutation has been found to be an oncogenic driver gene in non
      small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising
      results in this unique population, while little is known about its association
      with outcomes of chemotherapy. The aim of this study was to investigate the
      efficacy of first line chemotherapy in patients with advanced HER2-mutant lung
      adenocarcinomas. METHODS: Patients with advanced NSCLC(N = 1714) initially
      underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements,
      and negative cases were then assessed for HER2 mutations using the method of
      amplification refractory mutation system(ARMS). The efficacy of first line
      pemetrexed-based chemotherapy was investigated in patients with HER2-mutant and
      those with EGFR-mutant, ALK/ROS1-rearranged and KRAS-mutant advanced
      adenocarcinomas. RESULTS: HER2 mutations were detected in 29 of 572(5.1%)
      specimens from a selected population of EGFR/KRAS/BRAF/ALK/ROS1 negative
      patients. All of them are adenocarcinomas. Among patients with HER2-mutant lung
      cancers, 25 received pemetrexed-based first line chemotherapy. The objective
      response rate(ORR) was 36.0%. Their median progression free survival(PFS) was 5.1
      months, which was similar with that of KRAS-mutant group (n = 40,5.0 months, p =
      0.971), numerically shorter than that of EGFR-mutant group(n = 74, 6.5 months, p
      = 0.247) and statistically significantly shorter than that of ALK/ROS1-rearranged
      group (n = 39,9.2 months, p = 0.004). Furthermore, HER2 variants subgroup
      analysis showed that PFS was inferior in A775_G776insYVMA group compared with
      other variants (4.2 vs 7.2 months, p = 0.085). CONCLUSIONS: Patients with
      advanced HER2-mutant lung adenocarcinomas showed an inferior outcome of first
      line pemetrexed-based chemotherapy compared to those with ALK/ROS1
      rearrangements, which strengthen the need for effective HER2-targeted drugs in
      clinical practice.

PMID- 29587668
TI  - Knockdown delta-5-desaturase in breast cancer cells that overexpress COX-2
      results in inhibition of growth, migration and invasion via a dihomo-gamma
      linolenic acid peroxidation dependent mechanism.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional
      membrane-bound enzyme that typically metabolizes arachidonic acid (downstream
      omega-6 fatty acid) to form 2-series of prostaglandins known to be involved in
      cancer development. Overexpression of COX-2 has been found in a majority of
      breast carcinomas, and has also been associated with increased severity and the
      development of the metastasis. Our lab recently demonstrated that COX-2 can also
      metabolize dihomo-gamma-linolenic acid (DGLA, a precursor of omega-6 arachidonic
      acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that
      can inhibit growth and migration of colon and pancreatic cancer cells. We thus
      tested whether our strategy of knocking down delta-5-desaturase (D5D, the key
      enzyme that converts DGLA to arachidonic acid) in breast cancer cells
      overexpressing COX-2 can also be used to promote 8-HOA formation, thereby
      suppressing cancer growth, migration, and invasion. METHODS: SiRNA and shRNA
      transfection were used to knock down D5D expression in MDA-MB 231 and 4 T1 cells
      (human and mouse breast cancer cell lines expressing high COX-2, respectively).
      Colony formation assay, FITC Annexin V/PI double staining, wound healing and
      transwell assay were used to assess the effect of our strategy on inhibition of
      cancer growth, migration, and invasion. GC/MS was used to measure endogenous 8
      HOA, and western blotting was performed to evaluate the altered key protein
      expressions upon the treatments. RESULTS: We demonstrated that D5D knockdown
      licenses DGLA to inhibit growth of breast cancer cells via promoting formation of
      8-HOA that can inhibit histone deacetylase and activate cell apoptotic proteins,
      such as procaspase 9 and PARP. Our strategy can also significantly inhibit cancer
      migration and invasion, associated with altered expression of MMP-2/- 9, E
      cadherin, vimentin and snail. In addition, D5D knockdown and DGLA supplementation
      greatly enhanced the efficacy of 5-fluorouracil on breast cancer growth and
      migration. CONCLUSIONS: Consistent to our previous studies on colon and
      pancreatic cancer, here we demonstrate again that the high level of COX-2 in
      breast cancer cells can be capitalized on inhibiting cancer growth and migration.
      The outcome of this translational research could guide us to develop new anti
      cancer strategy and/or to improve current chemotherapy for breast cancer
      treatment.

PMID- 29587669
TI  - Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker
      for tumor progression in cervical cancer.
AB  - BACKGROUND: Cervical cancer (CC) is the fourth cause of mortality by neoplasia in
      women worldwide. The use of immunomarkers is an alternative tool to complement
      currently used algorithms for detection of cancer, and to improve selection of
      therapeutic schemes. Aberrant expression of Ezrin and E-cadherin play an
      important role in tumor invasion. In this study we analyzed Ezrin and E-cadherin
      expression in liquid-based cervical cytology samples, and evaluated their
      potential use as prognostic immunomarkers. METHODS: Immunocytochemical staining
      of Ezrin and E-cadherin was performed in cervical samples of 125 patients. The
      cytological or histological diagnostic was performed by Papanicolaou staining or
      H&E staining, respectively. HPV genotyping was determined using INNO-LIPA
      Genotyping Extra kit and the HPV physical status by in situ hybridization. Ezrin
      expression in HaCaT, HeLa and SiHa cell lines was determined by
      immunocytochemistry, immunofluorescence and Western blot. RESULTS: High Ezrin
      expression was observed in cervical cancer samples (70%), samples with multiple
      infection by HR-HPV (43%), and samples with integrated viral genome (47%). High
      Ezrin expression was associated with degree of SIL, viral genotype and physical
      status. In contrast, low E-cadherin expression was found in cervical cancer
      samples (95%), samples with multiple infection by HR-HPV/LR-HPV (87%) and
      integrated viral genome (72%). Low E-cadherin expression was associated with
      degree of SIL and viral genotype. Interestingly, Ezrin nuclear staining was
      associated with degree of SIL and viral genotype. High Ezrin expression, high
      percent of nuclear Ezrin and low E-cadherin expression behaved as risk factors
      for progression to HSIL and cervical cancer. CONCLUSIONS: Ezrin and E-cadherin
      expression profile in cervical cytology samples could be a potential prognostic
      marker, useful for identifying cervical lesions with a high-risk of progression
      to cervical cancer.

PMID- 29587670
TI  - To fast, or not to fast before chemotherapy, that is the question.
AB  - Fasting in disease prevention and treatment has recently become a popular topic,
      particularly in the context of oncology. Unfortunately, the growing attention
      paid by the media has created a background of speculations and ambiguous
      messages. The attitude towards the role of fasting in cancer patients should be
      very cautious, as the risk of malnutrition/sarcopenia and disinformation may be
      associated with this approach. Whether the results obtained by fasting in the
      cellular and animal models can be transferred to cancer patients is still to be
      ascertained. At the moment, more preclinical studies are required to determine in
      which cancers, at which stage, and in what combinations fasting, fasting
      mimicking diets or caloric restriction mimetics may prove effective. So, despite
      the "rumors" of marketing and media, nowadays fasting and calorie restriction
      around CT represent only a promising intuition, which requires proper efforts and
      time to be validated by evidence-based clinical data.

PMID- 29587671
TI  - Coexisting of bone marrow fibrosis, dysplasia and an X chromosomal abnormality in
      chronic neutrophilic leukemia with CSF3R mutation: a case report and literature
      review.
AB  - BACKGROUND: Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative
      neoplasm (MPN) with less than 40 cases of patients being reported or clinically
      suspected meeting with 2008 World Health Organization ("WHO") diagnostic
      criteria. The current diagnosis of CNL remains to exclude other diseases.
      Recently, a new biomarker of CSF3R mutations that is almost invariably present in
      CNL has been identified. There is no effective treatment for CNL, therefore
      prognosis of the disease is poor, but it may be attributed to the presence of
      both SETBP1 and CSF3R gene mutations. The presence or absence of CSF3R mutation
      did not affect survival, whereas a trend for shortened survival was observed
      among patients with SETBP1-mutation. CASE PRESENTATION: Here we report a 65-year
      old woman patient who presented with leukocytosis without sign of fever and
      tumors. Bone marrow aspirates showed a markedly hypercellular feature with 76%
      92% myeloid and the dysplastic changes were found in about 7% of neutrophils
      cells. The bone marrow biopsy demonstrated marrow fibrosis with Gomori staining
      positive (+++~++++). Cytogenetic analysis showed 46,X,del (X) (q22). No molecular
      markers of BCR/ABL1 rearrangement (P210, P230, P190 and variably), JAK2V617F,
      FIP1L1-PDGFRA, TEL-PDGFRB, ZNF198-FGFR1 and SETBP1 mutations were identified,
      however, the CSF3R gene membrane proximal mutation (c.1853C > T/p.T618I sites)
      was detected by PCR techniques. The patient was diagnosed with CNL and died in
      about 2 months after disease diagnosis. CONCLUSION: In clinical course, the CNL
      concurrently with severe bone marrow fibrosis and dysplastic features as well as
      X chromosomal abnormality may predict a worsening prognosis regardless of SETBP1
      mutation status.

PMID- 29587672
TI  - Characteristics of patients with depression initiating or switching
      antidepressant treatment: baseline analyses of the PERFORM cohort study.
AB  - BACKGROUND: Patients who require a switch in their antidepressant therapy may
      have different clinical profiles and treatment needs compared with patients
      initiating or maintaining a first-line antidepressant therapy. METHODS: The
      Prospective Epidemiological Research on Functioning Outcomes Related to Major
      depressive disorder (MDD) (PERFORM) study was a 2-year observational cohort study
      in outpatients with MDD in five European countries. Enrolled patients were either
      initiating or undergoing the first switch to an antidepressant monotherapy.
      Baseline data on patients' clinical status, functioning, productivity, quality of
      life and medical-resource use were compared in a cross-sectional baseline
      analysis. RESULTS: A total of 1402 patients were enrolled, of whom 1159 (82.7%)
      provided analysable baseline data. The majority (78.7%) of the analysable
      population were initiating antidepressant treatment and most (83.6%) were
      enrolled and followed up by general practitioners. Compared with patients
      initiating antidepressants, those switching antidepressants (21.3%) tended to
      have more severe depressive symptoms, greater anxiety, worse health-related
      quality of life, greater functional impairment, greater medical-resource use and
      had a different medical history. Limitations included an over-representation of
      switches due to lack of efficacy among patients who were switching treatment, as
      patients were selected based on presence of depressive symptoms. CONCLUSIONS:
      Patients with MDD who are switching treatment for the first time have a different
      profile and different depression-associated health needs compared with those
      initiating treatment. Therapeutic management should therefore be adapted for
      patients who switch. TRIAL REGISTRATION: ClinicalTrials.gov NCT01427439 ;
      Retrospectively registered 26 August 2011.

PMID- 29587673
TI  - A randomised controlled trial of the effectiveness of a breastfeeding training
      DVD on improving breastfeeding knowledge and confidence among healthcare
      professionals in China.
AB  - BACKGROUND: Despite almost all babies being breastfed initially, the exclusive
      breastfeeding rate at six months is less than 30% in China. Improving
      professionals' knowledge and practical skill is a key government strategy to
      increase breastfeeding rates. This study aimed to test the effectiveness of a
      breastfeeding DVD training method for clinicians on improving their knowledge and
      confidence in the breastfeeding support skills of teaching mothers Positioning
      and Attachment (P & A) and Hand Expression (HE). METHODS: A randomised controlled
      trial was conducted in three hospitals in Zhejiang province, China in 2014.
      Participants were recruited before their routine breastfeeding training course
      and randomly allocated to intervention group (IG) and control group (CG). The 15
      min "Breastfeeding: Essential Support Skills DVD" was the intervention for IG and
      a vaginal delivery DVD was used for CG. All participants completed questionnaires
      of job information, knowledge and confidence in the two skills before (baseline)
      and immediately after viewing the DVD (post DVD). RESULTS: Out of 210
      participants, 191 completed knowledge assessments before and after watching the
      DVD (IG n = 96, CG n = 95), with the response rate of 91.0%. At baseline, there
      are no significant differences in job variables, total knowledge scores and
      confident scores. The total knowledge score significantly increased post-DVD for
      IG (pre-DVD: M = 5.39, SD = 2.03; post-DVD: M = 7.74, SD = 1.71; t (95) = -
      10.95, p < 0.01), but no significant change in total knowledge score for CG
      between pre- and post-DVD (pre-DVD: M = 5.67, SD = 1.70; post-DVD: M = 5.56, SD =
      1.63; t (94) = 0.85). The total confidence scores were significantly higher post
      DVD than pre-DVD in IG (pre-DVD: M = 66.49, SD = 11.27; post- DVD: M = 71.81, SD
      = 9.33; t (68) = - 4.92, p < 0.01), but no significant difference was seen in CG
      between pre- and post-DVD total confidence scores (pre-DVD: M = 68.33, SD =
      11.08; post-DVD: M = 68.35, SD = 11.40; t (65) = - 0.25). Personal and job
      variables did not mediate these effects. CONCLUSIONS: The breastfeeding training
      DVD improved professionals' knowledge and confidence of the two breastfeeding
      support skills. However, the effect on professionals' practice and on
      breastfeeding outcomes needs to be examined in the future.

PMID- 29587674
TI  - Androgen receptor in advanced breast cancer: is it useful to predict the efficacy
      of anti-estrogen therapy?
AB  - BACKGROUND: Androgen receptor (AR) is widely expressed in breast cancer (BC) but
      its role in estrogen receptor (ER)-positive tumors is still controversial. The
      AR/ER ratio has been reported to impact prognosis and response to antiestrogen
      endocrine therapy (ET). METHODS: We assessed whether AR in primary tumors and/or
      matched metastases is a predictor of efficacy of first-line ET in advanced BC.
      Patients who had received first-line ET (2002-2011) were recruited, while those
      given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of
      chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR
      expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent
      in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to
      categorize AR expression. RESULTS: Among 102 evaluable patients, biomarkers were
      assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients
      having both determinations. The overall concordance rate between primary tumors
      and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not
      affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR >=0.96 was
      associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p =
      0.028). AR status in primary tumors or metastases was not associated with
      progressive disease (PD) as best response. In contrast, Ki67 >= 20% and PgR < 10%
      showed a statistically significant association with PD as best response.
      CONCLUSIONS: AR expression does not appear to be useful to predict the efficacy
      of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its
      efficacy.

PMID- 29587675
TI  - Expression of Reg IV and SOX9 and their correlation in human gastric cancer.
AB  - BACKGROUND: Reg IV is a member of the regenerating gene family and has been
      demonstrated to be overexpressed in gastric cancer. However, the functional
      mechanism of Reg IV in gastric cancer is still unclear. METHODS: Expression of
      Reg IV and SOX9 were investigated by immunohistochemistry (IHC) and real-time
      PCR, and the correlation between the expression of Reg IV and SOX9 was analyzed
      in gastric cancer tissues. Reg IV expression vectors and a siRNA of Reg IV and
      SOX9 were transfected into human gastric cancer cells and the protein and mRNA
      levels of Reg IV and SOX9 were investigated by western blot and real-time PCR.
      The invasion and migration ability of gastric cancer cells with overexpressed Reg
      IV and with gene silence of Reg IV and SOX9 were examined by transwell chambers
      and wound healing assay. RESULTS: The Reg IV and SOX9 protein expression levels
      were both significantly higher in gastric cancer tissues compared with adjacent
      tissues (p = 0.022, p = 0.003). Reg IV protein expression significantly
      correlated with tumor invasion depth (p <  0.001), but had no significant
      correlations with age, clinical stage or lymph node metastasis. SOX9 protein
      expression also had no significant correlations with age, clinical stage, tumor
      invasion depth or lymph node metastasis. Reg IV transcript expression
      demonstrated a significant correlation with invasion depth and lymph node
      metastasis (p = 0.005, p <  0.001) and no significant correlations with age,
      clinical stage, tumor tissue differentiation or tumor size. SOX9 transcript
      expression demonstrated a significant correlation with invasion depth and tumor
      tissue differentiation (p = 0.044, p = 0.007) and no significant correlations
      with age, clinical stage or tumor size. The Reg IV expression showed a positive
      correlation with the SOX9 expression (p <  0.000, p = 0.008). Overexpression of
      Reg IV could upregulate SOX9 expression and promote invasiveness and migration of
      tumor cells, and silencing of Reg IV could downregulate SOX9 and inhibit
      invasiveness and migration of tumor cells in MKN-45 and AGS cells. On the other
      hand, silencing of SOX9 could upregulate Reg IV protein expression. CONCLUSIONS:
      Our study demonstrated that Reg IV positively regulates the expression of SOX9
      and is involved in tumor cell invasion and migration in gastric cancer.

PMID- 29587676
TI  - 'Whose Shoes?' Can an educational board game engage Ugandan men in pregnancy and
      childbirth?
AB  - BACKGROUND: Men can play a significant role in reducing maternal morbidity and
      mortality in low-income countries. Maternal health programmes are increasingly
      looking for innovative interventions to engage men to help improve health
      outcomes for pregnant women. Educational board games offer a unique approach to
      present health information where learning is reinforced through group discussions
      supporting peer-to-peer interactions. METHODS: A qualitative study with men from
      Uganda currently living in the UK on their views of an educational board game.
      Men were purposively sampled to play a board game and participate in a focus
      group discussion. The pilot study explored perceptions on whether a board game
      was relevant as a health promotional tool in maternal health prior to
      implementation in Uganda. RESULTS: The results of the pilot study were promising;
      participants reported the use of visual aids and messages were easy to understand
      and enhanced change in perspective. Men in this study were receptive on the use
      of board games as a health promotional tool and recommended its use in rural
      Uganda. CONCLUSIONS: This study provides preliminary data on the relevancy and
      efficacy of using board games in maternal health. Key messages from the focus
      group appeared to be that the board game is more than acceptable to fathers and
      that it needs to be adapted to the local context to make it suitable for men in
      rural Uganda.

PMID- 29587677
TI  - A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric
      cancer.
AB  - BACKGROUND: We conducted a phase I/Ib, open-label, single-arm trial to assess the
      safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine
      in patients with advanced gastric cancer. METHODS: Patients with advanced gastric
      cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was
      administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to
      evaluate the safety, immunological response and schedule. Based on the highest
      specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the
      ELISPOT test, cohorts were expanded to define the optimal dosing schedule for
      OTSGC-A24. RESULTS: In this study, 24 advanced gastric cancer patients with HLA
      A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w
      cohort: 11 and 1w cohort: 10 patients). The most common adverse events were
      decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common
      treatment-related adverse event was injection site erythema (25%). No dose
      limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated.
      Positive CTL responses after vaccination were observed in 15 patients (75%) at 4
      weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18
      patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort
      (78%). The best radiological was stable disease (40%). Median progression free
      survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7
      months (95% CI 3.8 to 8.6). CONCLUSIONS: OTSGC-A24 combined peptide cancer
      vaccine was well tolerated. Significant responses in CTL were observed and the
      recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although
      no radiological response was observed, a respectable overall survival was
      achieved, consistent with other immunotherapy agents being investigated in
      gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01227772 ,
      Date registered: 21 Oct 2010.

PMID- 29587678
TI  - A national cross-sectional study of adherence to timely mammography use in Malta.
AB  - BACKGROUND: Routine mammography improves survival. To achieve health benefits,
      women must attend breast screening regularly at recommended time intervals.
      Maltese women are routinely invited to undergo mammography at three-year
      intervals at an organized breast screening programme (MBSP) or can opt to attend
      a private clinic. Previous research shows that health beliefs, particularly
      perceived barriers, were the most significant predictors of uptake to the first
      MBSP invitation. Whether these beliefs and other factors are predictive of
      adherence with recommended time intervals for mammography at organized or private
      screening in Malta is unknown. For the first time, this paper explores the
      predictors for Maltese women screened within or exceeding the recommended three
      year frequency in organized or private screening in Malta. METHODS: Information
      was obtained from a cross-sectional survey of 404 women, aged 50 to 60 years at
      the time of their first MBSP invitation, where women's characteristics,
      knowledge, health beliefs and illness perceptions were compared. The main
      variable of interest was women's mammography attendance within a three-year
      interval (ADHERENT) or exceeding three years (NON-ADHERENT). Data were analysed
      using descriptive statistics, chi-square test, Mann Whitney test, Independent
      Samples t-test and Shapiro Wilk test. RESULTS: At the time of the survey, 80.2%
      (n = 324) had been screened within three years (ADHERENT), 5.9% (n = 24) had
      exceeded the three-year frequency (NON-ADHERENT) while 13.9% (n = 56) never had a
      mammogram. No significant associations were found between ADHERENT or NON
      ADHERENT women in relation to sociodemographic or health status variables (p >
      0.05). Knowledge of screening frequency was significantly associated with women's
      mammography adherence (chi2 = 5.5, p = 0.020). Health beliefs were the strongest
      significant predictors to describe the variance between ADHERENT and NON-ADHERENT
      screeners. When Mann Whitney test and Independent Samples t-test were applied on
      mammography adherence, perceived barriers and cues to action were found to be the
      most important predictors (p = 0.000, p = 0.039 respectively). CONCLUSIONS: To
      increase routine and timely mammography practices, women who are non-adherent to
      recommended time frequency guidelines should be targeted, together with their
      health beliefs, predominantly perceived barriers and cues to action.

PMID- 29587680
TI  - A case of silicone oil adhered to the retinal surface via perfluorocarbon liquid.
AB  - BACKGROUND: Perfluorocarbon liquid (PFCL) is widely used as an intraoperative
      heavy tamponade to flatten the retina and is replaced with silicone oil (SO) at
      the end of the surgery. Due to the long tamponade period, the SO is known to
      remain attached to the retina at the time of removal, and is commonly termed
      "sticky oil". The aim of this present study was to report a case of SO stickily
      attached to the retina via PFCL without tamponade period. CASE PRESENTATION: A 39
      year-old male was referred to our hospital due to decreased vision and visual
      field defect in his right eye. Upon examination, he was diagnosed with
      rhegmatogenous retinal detachment in that eye. For treatment, he underwent
      vitrectomy with the use of PFCL and SO. The direct exchange of PFCL with SO
      resulted in residual subretinal fluid, so we subsequently attempted to remove the
      SO. However, a SO bubble adhering to the PFCL was visible on the posterior pole.
      After aspiration of the PFCL beneath the sticky SO, the SO was easily separated
      and removed from the retina. CONCLUSIONS: Our findings show that SO can become
      tightly adhered to the retinal surface via PFCL during vitrectomy, and that the
      sticky SO can be safely removed via aspiration of the PFCL layer underneath the
      SO.

PMID- 29587681
TI  - Association between age factors and strategies for promoting participation in
      gastric and colorectal cancer screenings.
AB  - BACKGROUND: Despite the long history of cancer screening in Japan, the
      participation rates in gastric and colorectal cancer screenings have not
      increased. Strategies for improving the participation rates have been proposed,
      but differences in their effects among different age groups remain unclear.
      METHODS: The Japanese government conducted a national survey in all
      municipalities in Japan in 2010 to investigate whether the implementation of
      promotion strategies increased participation in cancer screening. We investigated
      the association between age factors and strategies for promoting participation in
      cancer screening based on this national survey. Multiple regression analysis with
      generalized linear model was performed using the participation rates in gastric
      and colorectal cancer screenings as dependent variables, and the following
      strategies for promoting participation as independent variables: 1) personal
      invitation letters, 2) household invitation letters, 3) home visits by community
      nurses, 4) screenings in medical offices, and 5) free cancer screening programs.
      RESULTS: One thousand six hundred thirty nine municipalities for gastric cancer
      screening and 1666 municipalities for colorectal cancer screening were selected
      for the analysis. In gastric and colorectal cancer screenings, the participation
      rates of individuals aged 60-69 years was higher than those of other age groups.
      Personal and household invitation letters were effective promotion strategies for
      all age groups, which encouraged even older people to participate in gastric and
      colorectal cancer screenings. Screening in medical offices and free screenings
      were not effective in all age groups. Home visits were effective, but their
      adoption was limited to small municipalities. CONCLUSIONS: To clarify whether
      promotion strategies can increase the participation rate in cancer screening
      among different age groups, 5 strategies were assessed on the basis of a national
      survey. Although personal and household invitation letters were effective
      strategies for promoting participation in cancer screening for all age groups,
      these strategies equally encouraged older people to participate in gastric and
      colorectal cancer screenings. If resource for sending invitation letters are
      limited, priority should be given to individuals who are in their 50s and 60s for
      gastric and colorectal cancer screening.

PMID- 29587679
TI  - Activated innate lymphoid cell populations accumulate in human tumour tissues.
AB  - BACKGROUND: Innate lymphoid cells (ILC) are part of a heterogeneous family of
      haematopoietic effector cells which lack re-arranged antigen-specific receptors.
      They promote host defense and contribute to tissue and metabolic homeostasis,
      wound healing and immune surveillance. Their role in human cancer immunity is
      less defined, and therefore we aimed to identify the frequency and phenotype of
      distinct ILC groups in various types of cancer. METHODS: Tissue samples and
      peripheral blood were collected from patients undergoing surgical resection of
      gastrointestinal and breast tumours. Single cell suspension of tumour tissue was
      immediately obtained following surgery using tumour dissociation. RESULTS: We
      observed significantly higher frequencies of ILC2 (p value: 0.04) in malignant
      breast cancer tissue and significantly higher frequencies of group 1 ILC (p
      value: 0.001) in malignant gastrointestinal tumours. Tumour infiltrating ILC were
      found to show an activated phenotype with higher expression of MHC-II, KLRG1,
      early activation marker CD69 and CD44. CONCLUSIONS: Activated innate lymphoid
      cells infiltrate tumours dependent on tumour type and location.

PMID- 29587682
TI  - Impact of a behaviorally-based weight loss intervention on parameters of insulin
      resistance in breast cancer survivors.
AB  - BACKGROUND: Breast cancer survivors with excess weight are more likely to have
      negative breast cancer outcomes. Biomarkers related to insulin resistance may
      help explain this negative association. Weight loss is associated with
      improvements in insulin sensitivity. Our goal was to identify the impact of a
      behaviorally based weight loss intervention on indices of insulin resistance.
      METHODS: Overweight, early stage breast cancer survivors who completed initial
      cancer therapy were enrolled in a 6 month behaviorally based weight loss
      intervention that included calorie reduction, exercise and behavior modification.
      Biomarkers related to insulin resistance were obtained at baseline and after the
      intervention. Results from participants who achieved >=5% weight loss were
      compared to those who lost less weight. RESULTS: Despite not having diabetes as a
      preexisting diagnosis prior to the study, 69% of all participants were considered
      to have pre-diabetes or diabetes at baseline based on American Diabetes
      Association definitions. Participants who achieved >=5% weight loss had
      significantly lower fasting insulin, AUC insulin, and insulin resistance as
      measured by HOMA-IR. Beta cell function decreased as anticipated when insulin
      resistance improved. Additionally, leptin levels declined. CONCLUSIONS: Breast
      cancer survivors who achieved >=5% weight loss demonstrated significant
      improvements in indices of insulin resistance. Despite an exclusion criteria of
      diabetes at the time of enrolment, a high proportion met criteria for pre
      diabetes or diabetes at baseline. Pre-diabetes appears to be under recognized in
      overweight breast cancer survivors. Behaviorally based weight loss interventions
      can result in weight loss and improvements in biomarkers related to breast cancer
      outcomes and additionally may decrease the chance of developing diabetes. TRIAL
      REGISTRATION: NCT01482702 4/12/2010 (retrospectively registered). 
      https://clinicaltrials.gov/ct2/show/NCT01482702?term=Dittus&rank=4.

PMID- 29587683
TI  - Shorter survival in adolescent and young adult patients, compared to adult
      patients, with stage IV colorectal cancer in Japan.
AB  - BACKGROUND: The incidence of colorectal cancer in adolescent and young adult
      patients is increasing. However, survival and clinical features of young
      patients, especially those with stage IV disease, relative to adult patients
      remain unclear. METHODS: This retrospective single-institution cohort study was
      conducted at a tertiary care cancer center. Subjects were 861 consecutive
      patients who were diagnosed with stage IV colorectal cancer at the age of 15 to
      74 years and who were referred to the division of surgery or gastrointestinal
      oncology at the National Cancer Center Hospital from 1999 to 2013. Overall
      survival (OS) was investigated and clinicopathological variables were analyzed
      for prognostic significance. RESULTS: Of these, 66 (8%) were adolescent and young
      adult patients and 795 (92%) were adult patients. Median survival time was 13.6
      months in adolescent and young adult patients and 22.4 months in adult patients,
      and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant
      worse prognosis of adolescent and young adult patients (p = 0.042). However, age
      itself was not an independent factor associated with prognosis by multivariate
      analysis. When compared with adult patients, adolescent and young adult patients
      consisted of higher proportion of the patients who did not undergo resection of
      primary tumor, which was an independent factor associated with poor prognosis in
      multivariate analysis. In patients who did not undergo resection (n = 349), OS of
      adolescent and young adult patients were significantly worse (p = 0.033).
      CONCLUSIONS: Prognoses were worse in adolescent and young adult patients with
      stage IV colorectal cancer compared to adult patients in Japan, due to a higher
      proportion of patients who did not undergo resection with more advanced and
      severe disease, but not due to age itself.

PMID- 29587684
TI  - Delphinidin induced protective autophagy via mTOR pathway suppression and AMPK
      pathway activation in HER-2 positive breast cancer cells.
AB  - BACKGROUND: We have previously demonstrated the anticancer effect of
      anthocyanins. In this study, we explored the biological activities of
      delphinidin, the most common of the anthocyanidin monomers, that were related to
      autophagy in HER-2 positive breast cancer MDA-MB-453 and BT474 cells. METHODS:
      The effects of various doses of delphinidin on the proliferation and apoptosis of
      MDA-MB-453 and BT474 cells were analysed. Autophagy was identified as a critical
      factor that influenced chemotherapy, and the autophagic mechanism in delphinidin
      treated cells was investigated. The autophagy inhibitors, 3-MA and BA1, were used
      to analyse the effects of autophagy inhibition. RESULTS: Delphinidin inhibited
      proliferation, promoted apoptosis, and induced autophagy in MDA-MB-453 and BT474
      cells in a dose-dependent manner. The inhibition of autophagy enhanced the
      delphinidin-induced apoptosis and antiproliferative effect in both HER-2 positive
      breast cancer cells. In addition, delphinidin induced autophagy via suppression
      of the mTOR signalling pathway and activation of the AMPK signalling pathway in
      HER-2 positive breast cancer cells. CONCLUSIONS: Collectively, the results showed
      that delphinidin induced apoptosis and autophagy in HER-2 positive breast cancer
      cells and that autophagy was induced via the mTOR and AMPK signalling pathways.
      The suppression of autophagy promoted the anticancer effects of delphinidin.

PMID- 29587685
TI  - Quality of life of survivors of malignant pleural mesothelioma in Japan: a cross
      sectional study.
AB  - BACKGROUND: Previous studies have indicated that people with malignant pleural
      mesothelioma (MPM) have a poor quality of life (QOL); however, information about
      the QOL of people with MPM in Japan is anecdotal. The aims of this study were to
      investigate the QOL of survivors of MPM in Japan and to determine the factors
      that correlate with their QOL. METHODS: This was a cross sectional study. The
      included patients were those diagnosed with MPM in Japan. We created a self
      administered questionnaire consisting of 64 questions. The questionnaires were
      sent to hospitals and patient advocacy groups, distributed to the patients,
      completed, and sent back to the researchers by postal mail. QOL was assessed with
      the European Organization for Research and Treatment of Cancer 16 questionnaire
      (QLQ) and the short version of the core domains of the Comprehensive Quality of
      Life Outcome questionnaire (CoQoLo). RESULTS: In total, 133 questionnaires were
      collected. The QLQ assessments demonstrated that the survivors of MPM most
      frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The
      symptom scales were acceptable, but the functional scales were significantly
      poorer for the patients with poor performance statuses (PSs). The short CoQoLo
      assessment was very unfavorable for 'Being free from physical pain.' Being a long
      term survivor and a survivor with a poor PS were significantly correlated with
      poor global health status. CONCLUSIONS: Survivors of MPM have impaired function,
      a variety of symptoms, and lower QOL. Survivors of MPM, even those in good
      physical condition, need broad support.

PMID- 29587686
TI  - Information-based cues at point of choice to change selection and consumption of
      food, alcohol and tobacco products: a systematic review.
AB  - BACKGROUND: Reducing harmful consumption of food, alcohol, and tobacco products
      would prevent many cancers, diabetes and cardiovascular disease. Placing
      information-based cues in the environments in which we select and consume these
      products has the potential to contribute to changing these behaviours. METHODS:
      In this review, information-based cues are defined as those which comprise any
      combination of words, symbols, numbers or pictures that convey information about
      a product or its use. We specifically exclude cues which are located on the
      products themselves. We conducted a systematic review of randomised, cluster-
      randomised, and non-randomised controlled trials to assess the impact of such
      cues on selection and consumption. Thirteen studies met the inclusion criteria,
      of which 12 targeted food (most commonly fruit and vegetables), one targeted
      alcohol sales, and none targeted tobacco products. RESULTS: Ten studies reported
      statistically significant effects on some or all of the targeted products,
      although studies were insufficiently homogenous to justify meta-analysis.
      Existing evidence suggests information-based cues can influence selection and
      consumption of food and alcohol products, although significant uncertainty
      remains. CONCLUSIONS: The current evidence base is limited both in quality and
      quantity, with relatively few, heterogeneous studies at unclear or high risk of
      bias. Additional, more rigorously conducted studies are warranted to better
      estimate the potential for these interventions to change selection and
      consumption of food, alcohol and tobacco products. TRIAL REGISTRATION: PROSPERO.
      2016; CRD42016051884 .

PMID- 29587687
TI  - Above-versus below-elbow casting for conservative treatment of distal radius
      fractures: a randomized controlled trial and study protocol.
AB  - BACKGROUND: A variety of cast options are available for the non-surgical
      treatment of distal radius fractures (DRF) in adults. However, the literature is
      inconclusive regarding the need to immobilize the elbow joint after reduction in
      order to prevent rotation of the forearm in order to maintain the reduction of
      DRF. This study aimed to evaluate the best method of immobilization between above
      elbow (AE) and below-elbow (BE) cast groups at the end of six-month follow-up.
      METHODS: This is a randomized clinical trial with parallel groups and a blinded
      evaluator. There are two non-surgical interventions: AE and BE. Patients will be
      randomly assigned. A hundred twenty eight consecutive adult patients with acute
      (up to 7 days) displaced DRF of type A2, A3, C1, C2 or C3 by the
      Arbeitsgemeinschaft fur Osteosynthesefragen (AO) classification will be included.
      The primary outcome will be the maintenance of reduction by evaluation of
      radiographic parameters and Disabilities of the Arm, Shoulder and Hand
      Questionnaire (DASH). Secondary outcomes include function measured by Patient
      Rated Wrist Evaluation (PRWE), pain measured by the Visual Analogue Scale (VAS),
      objective functional evaluation (goniometry and dynamometry) and rate of
      complications. Evaluations will be performed at 1, 2, 3, 4, 6, 8, 12 and 24
      weeks. For the Student's t-test, a difference of 10 points in DASH score, with
      95% confidence interval, a statistical power of 95%, and 20% sampling error. We
      consider an extra 10% for balancing follow up losses results in 64 patients per
      group. DISCUSSION: Results from this study protocol will help to define the need
      for elbow immobilization in maintenance of reduction, as well as functional
      performance of below elbow cast versus above elbow cast immobilization during the
      immobilization period. TRIAL REGISTRATION: NCT03126175 (
      http://clinicaltrials.gov ). April 24, 2017.

PMID- 29587688
TI  - Computer-assisted cognitive remediation therapy increases hippocampal volume in
      patients with schizophrenia: a randomized controlled trial.
AB  - BACKGROUND: Cognitive remediation therapy (CRT) effectively reduces
      neurocognitive impairment in patients with schizophrenia, but few studies have
      used structural neuroimaging methods to assess its neuroanatomical effects. We
      investigated these effects, as well as the association between changes in
      cortical volume and neurocognitive performance. METHOD: Between August 2013 and
      September 2016, we performed a randomized controlled study comprising a CRT group
      (16 individuals) and a treatment-as-usual (TAU) group (15 individuals) of
      patients with schizophrenia. CRT participants engaged in twice-weekly computer
      assisted CRT sessions and weekly group meetings for 12 weeks. T1-weighted
      magnetic resonance imaging was performed before and after the intervention
      period, and whole-brain voxel-based morphometric analysis was used to detect
      significant cortical gray matter volume changes. We also assessed the correlation
      between cortical volume changes and CRT-derived neurocognitive improvements.
      RESULTS: The CRT group exhibited significantly greater improvements than the TAU
      group in verbal fluency (P = 0.012) and global cognitive scores (P = 0.049). The
      CRT group also exhibited significantly greater increases in right hippocampal
      volume than the TAU group (P < 0.001). Changes in verbal fluency scores and right
      hippocampal volumes were positively correlated (r = 0.53, P = 0.001). CONCLUSION:
      We found that CRT significantly increased right hippocampal volumes and that
      these enhancements were positively correlated with changes in verbal fluency
      scores. Our results indicate that CRT induces cognitive improvement through
      hippocampal plasticity. TRIAL REGISTRATION: Registration number: UMIN000026146 ,
      2017/02/15, retrospectively registered.

PMID- 29587689
TI  - Complementary feeding practices and associated factors in Damot Weydie District,
      Welayta zone, South Ethiopia.
AB  - BACKGROUND: Each year, more than millions of under-five children die due to under
      nutrition, and many of these deaths are associated with inappropriate feeding
      practices. This study aimed to assess complementary feeding practices in Damot
      Weydie District, South Ethiopia. METHODS: A community-based cross-sectional study
      was conducted among four-hundred and one mothers who had children aged 6-23
      months in Damot Weydie District. A pretested structured questionnaire was used to
      collect data using a face-to-face interview. Data were entered into Epi-Data
      version 3.1 and analysis was done by using Statistical Package for Social
      Sciences (SPSS) version 20. Multivariable logistic regressions were conducted to
      determine independent factors associated with complementary feeding practices.
      RESULTS: More than half (50.6%) of children were given complementary foods at six
      months of age. Only 8.5% of young children aged 6-23 months were fed with
      appropriate complementary foods. The proportion of mothers who reported that they
      know that a baby of 6-23 months old should be fed two or three times was only
      75.8%. Government-employed mothers (adjusted odds ratio (AOR) = 0.14(0.04, 0.50)
      and mothers who attended postnatal care (AOR = 0.19(0.05, 0.70) were less likely
      to practice inappropriate complementary feeding. Mothers having children with
      birth intervals less than 35 months were more likely to practice inappropriate
      complementary feeding when compared to mothers of children with birth intervals
      greater than 35 months (AOR = 2.67 (1.22, 5.83). CONCLUSIONS: Considerable
      proportions of infants and young children were not appropriately fed with
      complementary foods as per WHO recommendations. Being a government employee
      mother, attending postnatal care and having a child with birth interval greater
      than 3 years were associated with appropriate complementary feeding. Therefore,
      it is important to encourage postnatal care utilization and incorporate
      complementary feeding advice during postnatal visits. It is critical to raise the
      awareness of the community about optimal complementary feeding practices with
      special attention to unemployed and less educated mothers. Additionally, inter
      sectoral collaboration should be strengthened to increase the variety of food
      groups available.

PMID- 29587690
TI  - Evaluation of an interaction-skills training for reducing the burden of family
      caregivers of patients with severe mental illness: a pre-posttest design.
AB  - BACKGROUND: Family members who care for patients with severe mental illness
      experience emotional distress and report a higher incidence of mental illness
      than those in the general population. They report feeling inadequately prepared
      to provide the necessary practical and emotional support for these patients. The
      MAT training, an Interaction-Skills Training program (IST) for caregivers, was
      developed to meet those needs. This study used a single-arm pretest-posttest
      design to examine the impact of the training on caregivers' sense of competence
      (self-efficacy) and burden. METHODS: One hundred family caregivers recruited from
      three mental health institutions participated in the training. Burden was
      assessed using the Involvement Evaluation Questionnaire, and self-efficacy using
      the Self-Efficacy Questionnaire. Analysis of variance with repeated measures was
      used to investigate whether participation in the training changed the level of
      family caregivers' burden and self-efficacy. Pearson's correlation was used to
      examine the relationships between self-efficacy and burden. RESULTS: Our results
      indicate that, after the training, self-efficacy increased significantly over
      time (p < 0.001) and that burden decreased significantly (p < 0.001). However,
      the results could not demonstrate the expected association between an increase of
      self-efficacy and decrease of burden. Caregivers expressed high appreciation for
      the training. CONCLUSIONS: After following the IST program, family caregivers of
      patients with severe mental illness experienced a greater sense of competence and
      a significant decrease in burden. The training was greatly appreciated and
      satisfied caregivers' need to acquire the skills required in complex caregiving
      situations. TRIAL REGISTRATION: This study was retrospectively registered
      (14/01/2018) in the ISRCTN registry with study ID ISRCTN44495131 .

PMID- 29587691
TI  - Trends in unprotected intercourse among heterosexual men before and after brothel
      ban in Siem Reap, Cambodia: a serial cross-sectional study (2003-2012).
AB  - BACKGROUND: Following Cambodia's implementation of the 100% condom use program
      with enforcement of condom use and STI treatment services for sex workers in
      2001, sexually transmitted infection and HIV declined markedly. In 2008, Cambodia
      implemented a law to ban brothel-based sex work. We reported trends in
      unprotected vaginal intercourse with sex workers among heterosexual men buying
      sex before (2003-2008) and after (2009-2012) the brothel ban in Cambodia. We also
      determined the association of brothel ban with these men's reports of unprotected
      intercourse with sex workers. METHODS: In this serial cross-sectional study, we
      collected yearly behavioural data on random cross-sectional samples of
      heterosexual men buying sex who attended the only government health centre in
      Siem Reap for voluntary confidential counselling and testing (VCCT) between 2003
      and 2012. We used multivariable Poisson regression analysis on the 10-year data
      of 976 men to obtain the adjusted prevalence ratio (aPR) of unprotected
      intercourse in the last 6 months by brothel closure. RESULTS: Men buying sex from
      non-brothel-based sex workers increased almost 3-fold from 17% in 2007-2008
      before brothel closure to 55% in 2011-2012 after brothel closure (p < 0.001).
      Unprotected intercourse with sex workers in the last week increased significantly
      from 37% (2003-2004) before brothel closure to 65% (2011-2012) after brothel
      closure. This increase corresponded closely with the increase in self-reported
      unprotected intercourse from 35% to 61% by the sex workers (n = 1805) attending
      the same clinic for VCCT. Brothel closure was associated with an increased risk
      (aPR: 1.65; 95% CI: 1.40-1.94) of unprotected intercourse with sex workers. HIV
      prevalence in the heterosexual men declined significantly from 26% in 2003-2004
      to 4.8% in 2007-2008 and 0 case in 2009-2010 before increasing to 5.6% in 2011
      2012. CONCLUSION: Our findings suggest that the brothel ban had led to an
      increase in unprotected intercourse with all sex workers for men buying sex. This
      effect could be attributed to reduced condom access, a consequence of the lack of
      feasibility to implement the 100% condom use program following the brothel ban.
      The ban on brothels in Cambodia should be reviewed.

PMID- 29587692
TI  - Food safety labelling of chicken to prevent campylobacteriosis: consumer
      expectations and current practices.
AB  - BACKGROUND: Campylobacter is the leading cause of bacterial gastroenteritis
      worldwide, and contaminated chicken is a significant vehicle for spread of the
      disease. This study aimed to assess consumers' knowledge of safe chicken handling
      practices and whether their expectations for food safety labelling of chicken are
      met, as a strategy to prevent campylobacteriosis. METHODS: We conducted a cross
      sectional survey of 401 shoppers at supermarkets and butcheries in Wellington,
      New Zealand, and a systematic assessment of content and display features of
      chicken labels. RESULTS: While 89% of participants bought, prepared or cooked
      chicken, only 15% knew that most (60-90%) fresh chicken in New Zealand is
      contaminated by Campylobacter. Safety and correct preparation information on
      chicken labels, was rated 'very necessary' or 'essential' by the majority of
      respondents. Supermarket chicken labels scored poorly for the quality of their
      food safety information with an average of 1.7/5 (95% CI, 1.4-2.1) for content
      and 1.8/5 (95% CI, 1.6-2.0) for display. CONCLUSIONS: Most consumers are unaware
      of the level of Campylobacter contamination on fresh chicken and there is a
      significant but unmet consumer demand for information on safe chicken preparation
      on labels. Labels on fresh chicken products are a potentially valuable but
      underused tool for campylobacteriosis prevention in New Zealand.

PMID- 29587693
TI  - A case of allergic bronchopulmonary aspergillosis successfully treated with
      mepolizumab.
AB  - BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic
      pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus
      fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and
      pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard
      therapy for ABPA, but long-term use of systemic corticosteroids often causes
      serious side effects. CASE PRESENTATION: A 64-year-old woman was diagnosed with
      ABPA based on a history of bronchial asthma (from 40 years of age), elevated
      total IgE, the presence of serum precipitating antibodies and elevated specific
      IgE antibody to A. fumigatus, and pulmonary infiltration. Bronchoscopy showed
      eosinophilic mucoid impaction. Systemic corticosteroid therapy was initiated, and
      her symptoms disappeared. Peripheral eosinophilia and pulmonary infiltration
      recurred five months after cessation of corticosteroid treatment. Systemic
      corticosteroids were re-initiated and itraconazole was added as an anti-fungal
      agent. The patient was free of corticosteroids, aside from treatment with a short
      course of systemic corticosteroids for asthma exacerbation, and clinically stable
      with itraconazole and asthma treatments for 3 years. In 2017, she experienced
      significant deterioration. Laboratory examination revealed marked eosinophilia
      (3017/MUL) and a chest computed tomography (CT) scan demonstrated pulmonary
      infiltration in the left upper lobe and mucoid impaction in both lower lobes. The
      patient was treated with high-dose inhaled corticosteroid/long-acting beta
      agonist, a long-acting muscarinic antagonist, a leukotriene receptor antagonist,
      and theophylline; spirometry revealed a forced expiratory volume in 1 s (FEV1) of
      1.01 L. An uncontrolled asthma state was indicated by an Asthma Control Test
      (ACT) score of 18. Mepolizumab, 100 mg every 4 weeks, was initiated for the
      treatment of severe bronchial asthma with ABPA exacerbation. Bronchial asthma
      symptoms dramatically improved, and ACT score increased to 24, by 4 weeks after
      mepolizumab treatment. Peripheral eosinophil count decreased to 174/MUL.
      Spirometry revealed improvement of lung function (FEV1: 1.28 L). A chest CT scan
      demonstrated the disappearance of pulmonary infiltration and mucoid impaction.
      CONCLUSIONS: To our knowledge, this is the first case of ABPA to be treated with
      mepolizumab. Dramatic improvements were observed in symptoms, lung function,
      peripheral eosinophil counts, and chest images. Mepolizumab could serve as an
      alternative treatment with the potential to provide a systemic corticosteroid
      sparing effect.

PMID- 29587694
TI  - Calibration of the global physical activity questionnaire to Accelerometry
      measured physical activity and sedentary behavior.
AB  - BACKGROUND: Self-report questionnaires are a valuable method of physical activity
      measurement in public health research; however, accuracy is often lacking. The
      purpose of this study is to improve the validity of the Global Physical Activity
      Questionnaire by calibrating it to 7 days of accelerometer measured physical
      activity and sedentary behavior. METHODS: Participants (n = 108) wore an
      ActiGraph GT9X Link on their non-dominant wrist for 7 days. Following the
      accelerometer wear period, participants completed a telephone Global Physical
      Activity Questionnaire with a research assistant. Data were split into training
      and testing samples, and multivariable linear regression models built using
      functions of the GPAQ self-report data to predict ActiGraph measured physical
      activity and sedentary behavior. Models were evaluated with the testing sample
      and an independent validation sample (n = 120) using Mean Squared Prediction
      Errors. RESULTS: The prediction models utilized sedentary behavior, and moderate-
      and vigorous-intensity physical activity self-reported scores from the
      questionnaire, and participant age. Transformations of each variable, as well as
      break point analysis were considered. Prediction errors were reduced by 77.7
      80.6% for sedentary behavior and 61.3-98.6% for physical activity by using the
      multivariable linear regression models over raw questionnaire scores.
      CONCLUSIONS: This research demonstrates the utility of calibrating self-report
      questionnaire data to objective measures to improve estimates of physical
      activity and sedentary behavior. It provides an understanding of the divide
      between objective and subjective measures, and provides a means to utilize the
      two methods as a unified measure.

PMID- 29587695
TI  - Comparison between absorbable pins and mini-screw fixations for the treatment of
      radial head fractures Mason type II-III.
AB  - BACKGROUND: The treatment of comminuted radial head fractures can include
      prosthetic replacement or open reduction and internal fixation. The purpose of
      this study is to evaluate the results of two different internal fixation systems
      for Mason type II-III radial head fractures. METHODS: Between 2005 and 2015, 82
      patients were treated using pins and 65 patients by mini-screws. The follow-up
      protocol included: a clinical evaluation 15 days after surgery, and clinical and
      radiographic evaluations performed at 30 and 60 day intervals, unless any
      complications were reported by the patient. Over a period of at least 12-months
      of follow-up, patients were checked and interviewed. Clinical examinations
      included elbow range of motion (ROM), arm, shoulder and hand Disabilities,
      (DASH), and the Mayo Elbow Performance Score (MEPS). RESULTS: Sixty-one subjects
      who had been treated with mini-screws were clinically reviewed at a mean 47.3 +/-
      35.8 month of follow-up; all patients who had been treated using absorbable pins
      were evaluated at a mean 82.5 +/- 20.6 month of follow-up. No significant
      statistically differences were observed between the two groups in the mean ROM,
      DASH, and MEPS scores. Residual pain was reported in 15.8%of the patients treated
      by pins and 9.2% patients treated by mini-screws. Secondary displacement of
      fracture fragments was observed in 8.5% patients treated by pins and 1.6% using
      mini-screws. CONCLUSIONS: Both absorbable pins and mini-screws provided adequate
      strength and rigidity, allowing good clinical and functional scores at a mid-term
      follow-up. However, a higher rate of secondary displacement of the fracture
      fragments was reported among subjects who had been treated using absorbable pins.

PMID- 29587696
TI  - Does leaving an abusive partner lead to a decline in victimization?
AB  - BACKGROUND: This paper investigates gender differences in persistence of intimate
      partner violence (IPV), for those remaining or leaving an abusive relationship.
      We followed a sample of males and females to examine whether leaving an abusive
      partner may alter the continuity of victimization. METHODS: Data were taken from
      the 21 and 30-year follow-ups of the Mater Hospital and University of Queensland
      Study of Pregnancy (MUSP) in Australia. A cohort of 1265 respondents, including
      874 females and 391 males, completed a 21-item version of the Composite Abuse
      Scale. RESULTS: We found proportionally similar rates of IPV victimization for
      males and females at both the 21 and 30 year follow-ups. Females who reported
      they had an abusive partner at the 21 year follow-up were more likely to
      subsequently change their partner than did males. Harassment and then emotional
      abuse appeared to have a stronger association for females leaving a partner. For
      males, a reported history of IPV was not significantly associated with leaving
      the partner. There was no significant association between leaving (or not) a
      previous abusive relationship and later victimization, either for male or female
      respondents. CONCLUSION: Changing a partner does not interrupt the continuity of
      victimization either for male or female respondents, and previous IPV
      victimization remained a determining factor of re-abuse, despite re-partnering.

PMID- 29587697
TI  - Association between skirt size and chronic liver disease in post-menopausal
      women: a prospective cohort study within the United Kingdom Trial of Ovarian
      Cancer Screening (UKCTOCS).
AB  - BACKGROUND: We investigated the association between self-reported skirt size (SS)
      and change in SS, and incidence of chronic liver disease (CLD) in a prospective
      cohort study of women recruited to the UKCTOCS trial. METHODS: Women recruited to
      UKCTOCS in England without documented CLD self-reported their current UK SS
      during trial participation and were asked to recall their SS when aged in 20s
      (via completion of a questionnaire 3-5 years after recruitment). Participants
      were followed up via electronic health record linkage and hazard ratios (HR)
      calculated for incident liver-related events (LRE). RESULTS: Three hundred twenty
      two (0.3%) of 94,124 women experienced a first LRE. Compared to SS <= 16, rates
      of LRE were higher in the SS >= 18 groups (both when aged in 20s and at
      questionnaire completion). Event rates were higher if there was no change in SS
      or an increase in SS, compared to a decrease in SS. In the models adjusted for
      potential confounders, HRs for LRE were higher in the groups of women reporting
      SS >= 18 both when aged in 20s (HR = 1.39 (95% CI; 0.87-2.23)) and at
      questionnaire completion (HR = 1.37 (95% CI; 1.07-1.75)). Compared to a decrease
      in SS, HRs were higher in the no change (HR = 1.78 (95% CI; 0.95-3.34)) and
      increase (HR = 1.80 (95% CI; 1.01-3.21)) groups. CONCLUSION: CLD is associated
      with high SS and an increase in SS over time. These data suggest SS can be used
      in simple public health messages about communicating the risk of liver disease.
      TRIAL REGISTRATION: UKCTOCS is registered as an International Standard Randomised
      Controlled Trial, number ISRCTN22488978 . Registered 06/04/2000.

PMID- 29587698
TI  - A hybrid type I randomized effectiveness-implementation trial of patient
      navigation to improve access to services for children with autism spectrum
      disorder.
AB  - BACKGROUND: Significant racial, ethnic, and socioeconomic disparities exist in
      access to evidence-based treatment services for children with autism spectrum
      disorder (ASD). Patient Navigation (PN) is a theory-based care management
      strategy designed to reduce disparities in access to care. The purpose of this
      study is to test the effectiveness of PN a strategy to reduce disparities in
      access to evidence-based services for vulnerable children with ASD, as well as to
      explore factors that impact implementation. METHODS: This study uses a hybrid
      type I randomized effectiveness/implementation design to test effectiveness and
      collect data on implementation concurrently. It is a two-arm comparative
      effectiveness trial with a target of 125 participants per arm. Participants are
      families of children age 15-27 months who receive a positive screen for ASD at a
      primary care visit at urban clinics in Massachusetts (n = 6 clinics), Connecticut
      (n = 1), and Pennsylvania (n = 2). The trial measures diagnostic interval (number
      of days from positive screen to diagnostic determination) and time to receipt of
      evidence-based ASD services/recommended services (number of days from date of
      diagnosis to receipt of services) in those with PN compared to and activated
      control -Conventional Care Management - which is similar to care management
      received in a high quality medical home. At the same time, a mixed-method
      implementation evaluation is being carried out. DISCUSSION: This study will
      examine the effectiveness of PN to reduce the time to and receipt of evidence
      based services for vulnerable children with ASD, as well as factors that
      influence implementation. Findings will tell us both if PN is an effective
      approach for improving access to evidence-based care for children with ASD, and
      inform future strategies for dissemination. TRIAL REGISTRATION: NCT02359084
      Registered February 1, 2015.

PMID- 29587699
TI  - Use of intervention mapping to adapt a health behavior change intervention for
      endometrial cancer survivors: the shape-up following cancer treatment program.
AB  - BACKGROUND: About 80% of endometrial cancer survivors (ECS) are overweight or
      obese and have sedentary behaviors. Lifestyle behavior interventions are
      promising for improving dietary and physical activity behaviors, but the
      constructs associated with their effectiveness are often inadequately reported.
      The aim of this study was to systematically adapt an evidence-based behavior
      change program to improve healthy lifestyle behaviors in ECS. METHODS: Following
      a review of the literature, focus groups and interviews were conducted with ECS
      (n = 16). An intervention mapping protocol was used for the program adaptation,
      which consisted of six steps: a needs assessment, formulation of matrices of
      change objectives, selection of theoretical methods and practical applications,
      program production, adoption and implementation planning, and evaluation
      planning. Social Cognitive Theory and Control Theory guided the adaptation of the
      intervention. RESULTS: The process consisted of eight 90-min group sessions
      focusing on shaping outcome expectations, knowledge, self-efficacy, and goals
      about healthy eating and physical activity. The adapted performance objectives
      included establishment of regular eating, balanced diet, and portion sizes,
      reduction in sedentary behaviors, increase in lifestyle and organized activities,
      formulation of a discrepancy-reducing feedback loop for all above behaviors, and
      trigger management. Information on managing fatigue and bowel issues unique to
      ECS were added. CONCLUSIONS: Systematic intervention mapping provided a framework
      to design a cancer survivor-centered lifestyle intervention. ECS welcomed the
      intervention and provided essential feedback for its adaptation. The program has
      been evaluated through a randomized controlled trial.

PMID- 29587700
TI  - Serum (1->3)-beta-D-glucan and galactomannan levels in patients with cystic
      fibrosis: a retrospective cohort study.
AB  - BACKGROUND: Aspergillus fumigatus is frequently encountered in sputum samples of
      patients with cystic fibrosis (CF), which traditionally has been interpreted as
      saprophytic airway colonization. However, this mere bystander role has been
      challenged by recent data. There is now evidence that Aspergillus fumigatus
      accelerates the decline of pulmonary function. (1->3)-beta-D-glucan (BDG) and
      galactomannan (GM) are highly sensitive fungal biomarkers that are used to
      diagnose invasive fungal disease. However, their diagnostic value in CF patients
      is largely unknown. METHODS: We conducted a retrospective cohort study on 104 CF
      patients to determine whether serum BDG and GM levels correlate with parameters
      such as Aspergillus-positive sputum cultures and lung function. RESULTS:
      Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients
      (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were
      significantly higher than in those without persistent Aspergillus detection (89
      versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively).
      27 and 7 patients had elevated BDG (>= 60 pg/ml) or GM levels (> 0.5 ODI),
      respectivly. BDG and GM levels showed a significant correlation (p = 0.004).
      Patients with increased serum concentrations of BDG were more frequently
      Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower
      forced expiratory volume in one second (FEV1) than patients with a normal BDG
      (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or
      the growth of A. fumigatus, proved to be an independent predictor for the FEV1.
      CONCLUSIONS: CF patients with persistent Aspergillus detection have elevated BDG
      and GM levels which ranged between healthy and invasively infected patients.
      Serum BDG may be superior to GM and fungal culture in predicting an impaired lung
      function in CF patients.

PMID- 29587701
TI  - The application of system dynamics modelling to environmental health decision
      making and policy - a scoping review.
AB  - BACKGROUND: Policy and decision-making processes are routinely challenged by the
      complex and dynamic nature of environmental health problems. System dynamics
      modelling has demonstrated considerable value across a number of different fields
      to help decision-makers understand and predict the dynamic behaviour of complex
      systems in support the development of effective policy actions. In this scoping
      review we investigate if, and in what contexts, system dynamics modelling is
      being used to inform policy or decision-making processes related to environmental
      health. METHODS: Four electronic databases and the grey literature were
      systematically searched to identify studies that intersect the areas
      environmental health, system dynamics modelling, and decision-making. Studies
      identified in the initial screening were further screened for their contextual,
      methodological and application-related relevancy. Studies deemed 'relevant' or
      'highly relevant' according to all three criteria were included in this review.
      Key themes related to the rationale, impact and limitation of using system
      dynamics in the context of environmental health decision-making and policy were
      analysed. RESULTS: We identified a limited number of relevant studies (n = 15),
      two-thirds of which were conducted between 2011 and 2016. The majority of
      applications occurred in non-health related sectors (n = 9) including
      transportation, public utilities, water, housing, food, agriculture, and urban
      and regional planning. Applications were primarily targeted at micro-level
      (local, community or grassroots) decision-making processes (n = 9), with macro
      level (national or international) decision-making to a lesser degree. There was
      significant heterogeneity in the stated rationales for using system dynamics and
      the intended impact of the system dynamics model on decision-making processes. A
      series of user-related, technical and application-related limitations and
      challenges were identified. None of the reported limitations or challenges
      appeared unique to the application of system dynamics within the context of
      environmental health problems, but rather to the use of system dynamics in
      general. CONCLUSIONS: This review reveals that while system dynamics modelling is
      increasingly being used to inform decision-making related to environmental
      health, applications are currently limited. Greater application of system
      dynamics within this context is needed before its benefits and limitations can be
      fully understood.

PMID- 29587702
TI  - Change in muscle volume after steroid therapy in patients with myositis assessed
      using cross-sectional computed tomography.
AB  - BACKGROUND: Steroid therapy, a key therapy for inflammatory, allergic, and
      immunological disorders, is often associated with steroid myopathy as one of the
      side effects. Steroid therapy is considered the first-line therapy for myositis;
      however, there have been no reports strictly comparing the muscle mass in
      patients with myositis before and after steroid therapy. Thus, it is currently
      unclear whether steroid therapy for such patients affects muscle volume in
      addition to muscle strength. We aimed to determine the change in muscle mass
      after steroid therapy via cross-sectional computed tomography (CT) in patients
      with myositis. METHODS: Data from seven patients with myositis and eight
      controls, who were all treated with high doses of steroids, were assessed before
      and after steroid therapy. Clinical factors in patients with myositis included
      serum muscle enzyme levels and muscular strength. The cross-sectional area of
      skeletal muscle and the low muscle attenuation rate at the level of the caudal
      end of the third lumbar vertebra were obtained using CT and measured using an
      image analysis program for all patients. Data were subjected to statistical
      analysis using several well-established statistical tests. The Wilcoxon signed
      rank test was used for comparing paired data for each patient. The Mann-Whitney U
      test was used to compare sets of data sampled from two groups. The Spearman's
      rank correlation coefficient was used for determining the correlations between
      two variables. Statistical significance was set at p < 0.05. RESULTS: Muscular
      strength and serum muscle enzyme levels improved following steroid therapy in
      patients with myositis. In both groups, the cross-sectional areas of skeletal
      muscles decreased (myositis group: p = 0.0156; control group: p = 0.0391) and the
      low muscle attenuation rate tended to increase (myositis group: p = 0.0781;
      control group: p = 0.0547). In the myositis group, patients with chronic
      obstructive pulmonary disease showed a tendency toward muscle volume loss (p =
      0.0571). CONCLUSION: In patients with myositis treated with steroid therapy,
      muscle mass decreased after steroid therapy suggesting that the improvement in
      muscle strength was due to factors other than a change in muscle volume. Our
      study suggests the importance of therapies that not only improve muscle mass but
      also improve the quality of muscle strength.

PMID- 29587703
TI  - Programming and supervision of resistance training leads to positive effects on
      strength and body composition: results from two randomised trials of community
      fitness programmes.
AB  - BACKGROUND: Many sedentary adults have high body fat along with low fitness,
      strength, and lean body mass (LBM) which are associated with poor health
      independently of body mass. Physical activity can aid in prevention, management,
      and treatment of numerous chronic conditions. The potential efficacy of
      resistance training (RT) in modifying risk factors for cardiovascular and
      metabolic disease is clear. However, RT is under researched in public health. We
      report community-based studies of RT in sedentary (Study 1), and overweight and
      pre-diabetic (Study 2) populations. METHODS: Study 1 - A semi randomised trial
      design (48-weeks): Participants choosing either a fitness centre approach, and
      randomised to structured-exercise (STRUC, n = 107), or free/unstructured gym use
      (FREE, n = 110), or not, and randomised to physical-activity-counselling (PAC, n
      = 71) or a measurement only comparator (CONT, n = 76). Study 2 - A randomised
      wait list controlled trial (12-weeks): Patients were randomly assigned to;
      traditional-supervised-exercise (STRUC, n = 30), physical-activity-counselling
      (PAC, n = 23), either combined (COMB, n = 39), or a wait-list comparator (CONT, n
      = 54). Outcomes for both were BF mass (kg), LBM (kg), BF percentage (%), and
      strength. RESULTS: Study 1: One-way ANCOVA revealed significant between group
      effects for BF% and LBM, but not for BF mass or strength. Post hoc paired
      comparisons revealed significantly greater change in LBM for the STRUC group
      compared with the CONT group. Within group changes using 95%CIs revealed
      significant changes only in the STRUC group for both BF% (- 4.1 to - 0.9%) and
      LBM (0.1 to 4.5 kg), and in FREE (8.2 to 28.5 kg) and STRUC (5.9 to 26.0 kg) for
      strength. Study 2: One-way ANCOVA did not reveal significant between group
      effects for strength, BF%, BF mass, or LBM. For strength, 95%CIs revealed
      significant within group changes for the STRUC (2.4 to 14.1 kg) and COMB (3.7 to
      15.0 kg) groups. CONCLUSION: Strength increased in both studies across all RT
      treatments compared to controls, yet significant improvements in both strength
      and body-composition occurred only in programmed and/or supervised RT. As general
      increases in physical activity have limited impact upon body-composition, public
      health practitioners should structure interventions to include progressive RT.
      TRIAL REGISTRATION: Study 1: ISRCTN13024854 , retrospectively registered
      20/02/2018. Study 2: ISRCTN13509468 , retrospectively registered 20/02/2018).

PMID- 29587704
TI  - Supporting change in chronic disease risk behaviours for people with a mental
      illness: a qualitative study of the experiences of family carers.
AB  - BACKGROUND: People with a mental illness experience greater chronic disease
      morbidity and mortality, and associated reduced life expectancy, compared to
      those without such an illness. A higher prevalence of chronic disease risk
      behaviours (inadequate nutrition, inadequate physical activity, tobacco smoking,
      and harmful alcohol consumption) is experienced by this population. Family carers
      have the potential to support change in such behaviours among those they care for
      with a mental illness. This study aimed to explore family carers': 1) experiences
      in addressing the chronic disease risk behaviours of their family members; 2)
      existing barriers to addressing such behaviours; and 3) perceptions of potential
      strategies to assist them to provide risk behaviour change support. METHODS: A
      qualitative study of four focus groups (n = 31), using a semi-structured
      interview schedule, was conducted with carers of people with a mental illness in
      New South Wales, Australia from January 2015 to February 2016. An inductive
      thematic analysis was employed to explore the experience of carers in addressing
      the chronic disease risk behaviours. RESULTS: Two main themes were identified in
      family carers' report of their experiences: firstly, that health behaviours were
      salient concerns for carers and that they were engaged in providing support, and
      secondly that they perceived a bidirectional relationship between health
      behaviours and mental well-being. Key barriers to addressing behaviours were: a
      need to attend to carers' own well-being; defensiveness on behalf of the family
      member; and not residing with their family member; with other behaviour-specific
      barriers also identified. Discussion around strategies which would assist carers
      in providing support for health risk behaviours identified a need for improved
      communication and collaboration between carers and health services accessed by
      their family members. CONCLUSIONS: Additional support from general and mental
      health services accessed by family members is desired to assist carers to address
      the barriers to providing behaviour change support. Carers have the potential to
      support and extend health service interventions aimed at improving the chronic
      disease risk behaviours of people with a mental illness but may require
      additional information, and collaboration from services. Further research is
      needed to explore these constructs in a large representative sample.

PMID- 29587705
TI  - An empirical exploration of female child marriage determinants in Indonesia.
AB  - BACKGROUND: Child marriage, defined as marriage before age 18, is associated with
      adverse human capital outcomes. The child marriage burden remains high among
      female adolescents in Indonesia, despite increasing socioeconomic development.
      Research on child marriage in Southeast Asia is scarce. No nationally
      representative studies thus far have examined determinants of child marriage in
      Indonesia through multivariate regression modeling. METHODS: We used data from
      the nationally representative 2012 Indonesian Demographic and Health Survey and
      the Adolescent Reproductive Health Survey to estimate determinants of child
      marriage and marital preferences. We ran multivariate models to estimate the
      association between demographic and socioeconomic characteristics and the
      following early marriage outcomes: 1) ever been married or cohabited, 2) married
      or cohabited before 18 years, 3) married or cohabited before 16 years, 4) self
      reported marital-age preferences and 5) attitudes approving female child
      marriage. RESULTS: Among the child marriage research sample (n = 6578, females
      aged 20-24 at time of survey), approximately 17% and 6% report being married
      before 18 and 16 years old respectively. Among the marital preferences research
      sample (n = 8779, unmarried females 15-24), the average respondent preferred
      marriage at approximately 26 years and 5% had attitudes approving child marriage.
      Education, wealth and media exposure have protective effects across marriage
      outcomes, while rural residence is a risk factor for the same. There are
      significant variations by region, indicating roles of religious, ethnic and other
      geographically diverse factors. CONCLUSION: This research fills a gap in
      understanding of child marriage determinants in Indonesia. There appears to be
      little support for child marriage among girls and young women, indicating an
      entry point for structural interventions that would lead to lasting change.
      Future research efforts should prioritize rigorous testing of gender
      transformative education and economic strengthening interventions, including cost
      effectiveness considerations to better understand how interventions and policies
      can be leveraged to deliver on ending child marriage in Indonesia and globally.

PMID- 29587706
TI  - TB epidemiology: where are the young women? Know your tuberculosis epidemic, know
      your response.
AB  - BACKGROUND: The global predominance of tuberculosis in men has received
      significant attention. However, epidemiological studies now demonstrate that
      there is an increased representation of young women with tuberculosis, especially
      in high HIV burden settings where young women bear a disproportionate burden of
      HIV. The role of the HIV epidemic, as well as changes in behavioural, biological,
      and structural risk factors are explored as potential explanations for the
      increasing burden of tuberculosis in young women. DISCUSSION: As young women are
      particularly vulnerable to HIV infection in sub-Saharan Africa, it is
      unsurprising that the TB epidemic in this setting has become increasingly
      feminised. This age-sex trend of TB in South Africa is similar to WHO estimates
      for other countries with a high HIV prevalence where there are more female than
      male cases notified up to the age of 25 years. The high prevalence of anaemia of
      chronic disease in young women with HIV is an additional potential reason for
      their increased TB risk. The widespread use of injectable medroxyprogesterone
      acetate contraception, which has been shown to possess selective glucocorticoid
      effect and oestrogen suppression, in young women may be an important emerging
      biological risk factor for tuberculosis in young women. Behavioural factors such
      as alcohol use and tobacco smoking patterns are further factors which may be
      responsible for the narrowing of the sex gap in TB epidemiology. In comparison to
      the significantly higher alcohol consumption rates in men globally, there is a
      narrowing gap in alcohol consumption between the sexes in South Africa with
      alarming rates of alcohol abuse in young women. There is a similar narrowing of
      the tobacco smoking gap between the sexes in South Africa, with increasing
      smoking prevalence in young women. CONCLUSION: With nearly 70% of all TB patients
      being co-infected with HIV in our setting, it is not surprising that the age and
      sex distribution of TB is increasingly resembling the distribution of HIV in this
      region of dual hyperendemicity. New TB service design must begin to reflect the
      presence of young women as a significant group burdened by the disease.

PMID- 29587707
TI  - School practices to promote social distancing in K-12 schools: review of
      influenza pandemic policies and practices.
AB  - BACKGROUND: During an evolving influenza pandemic, community mitigation
      strategies, such as social distancing, can slow down virus transmission in
      schools and surrounding communities. To date, research on school practices to
      promote social distancing in primary and secondary schools has focused on
      prolonged school closure, with little attention paid to the identification and
      feasibility of other more sustainable interventions. To develop a list and
      typology of school practices that have been proposed and/or implemented in an
      influenza pandemic and to uncover any barriers identified, lessons learned from
      their use, and documented impacts. METHODS: We conducted a review of the peer
      reviewed and grey literature on social distancing interventions in schools other
      than school closure. We also collected state government guidance documents
      directed to local education agencies or schools to assess state policies
      regarding social distancing. We collected standardized information from each
      document using an abstraction form and generated descriptive statistics on common
      plan elements. RESULTS: The document review revealed limited literature on school
      practices to promote social distancing, as well as limited incorporation of
      school practices to promote social distancing into state government guidance
      documents. Among the 38 states that had guidance documents that met inclusion
      criteria, fewer than half (42%) mentioned a single school practice to promote
      social distancing, and none provided any substantive detail about the policies or
      practices needed to enact them. The most frequently identified school practices
      were cancelling or postponing after-school activities, canceling classes or
      activities with a high rate of mixing/contact that occur within the school day,
      and reducing mixing during transport. CONCLUSION: Little information is available
      to schools to develop policies and procedures on social distancing. Additional
      research and guidance are needed to assess the feasibility and effectiveness of
      school practices to promote social distancing.

PMID- 29587708
TI  - Gender differences in occupational exposure to carcinogens among Italian workers.
AB  - BACKGROUND: Many carcinogenic chemicals are still used or produced in several
      economic sectors. The aim of this study is to investigate differences in
      occupational exposure patterns to carcinogens by gender in Italy. METHODS:
      Information about the most common carcinogens recorded in the Italian
      occupational exposures database (SIREP) for the period 1996-2015 was retrieved.
      Descriptive statistics were calculated for exposure-related variables
      (carcinogenic agent, occupational group, economic activity sector, and workforce
      size). The chi-square(chi2) test was used to verify differences between genders,
      and logistic regression analysis was performed to evaluate the association
      between gender and risk of having higher exposure levels, after adjusting for
      age. Concurrent exposures to multiple carcinogens were investigated using the two
      step cluster analysis. RESULTS: A total of 166,617 exposure measurements were
      selected for 40 different carcinogens. Exposed workers were only in a small
      proportion women (9%), and mostly aged 20-44 years (70%) in both genders. Women
      were more likely to be exposed than men to higher levels for several carcinogens
      even after correction for age at exposure, and the exposure level was
      significantly (p < 0.01) associated with occupation, economic sector and
      workforce size. The five main clusters of co-exposures identified in the entire
      dataset showed a differential distribution across economic sectors between
      genders. CONCLUSIONS: The exposures to occupational carcinogens have
      distinguishing characteristics in women, that are explained in part by work and
      job segregation. Because of the presence of high-exposed groups of female workers
      in many industrial sectors, further research and prevention efforts are
      recommended.

PMID- 29587709
TI  - Limitations of the S-TOFHLA in measuring poor numeracy: a cross-sectional study.
AB  - BACKGROUND: Although the Short Test of Functional Health Literacy in Adults (S
      TOFHLA) is widely used, misidentification of individuals with low health literacy
      (HL) in specific HL dimensions, like numeracy, is a concern. We examined the
      degree to which individuals scored as "adequate" HL on the S-TOFHLA would be
      considered as having low HL by two additional numerical measures. METHODS:
      English-speaking adults aged 45-75 years were recruited from a large, urban
      academic medical center and a community foodbank in the United States.
      Participants completed the S-TOFHLA, the Subjective Numeracy Scale (SNS), and the
      Graphical Literacy Measure (GL), an objective measure of a person's ability to
      interpret numeric information presented graphically. Established cut-points or a
      median split classified participants and having high and low numeracy. RESULTS:
      Participants (n = 187), on average were: aged 58 years; 63% female; 70%
      Black/African American; and 45% had a high school degree or less. Of those who
      scored "adequate" on the S-TOFHLA, 50% scored low on the SNS and 40% scored low
      on GL. Correlation between the S-TOFHLA and the SNS Total was moderate (r = 0.22,
      n = 186, p = 0.01), while correlation between the S-TOFHLA and the GL Total was
      large (r = 0.53, n = 187, p <= 0.01). CONCLUSIONS: Findings suggest that the S
      TOFHLA may not capture an individuals' HL in the dimension of numeracy. Efforts
      are needed to develop more encompassing and practical strategies for identifying
      those with low HL for use in research and clinical practice. TRIAL REGISTRATION:
      NCT02151032 (retrospectively registered: May 30, 2014).

PMID- 29587710
TI  - Partner age differences and associated sexual risk behaviours among adolescent
      girls and young women in a cash transfer programme for schooling in Malawi.
AB  - BACKGROUND: Age disparities in sexual relationships have been proposed as a key
      risk factor for HIV transmission in Sub-Saharan Africa, but evidence remains
      inconclusive. The SIHR study, a cluster randomised trial of a cash transfer
      programme in Malawi, found that young women in the intervention groups were less
      likely to have had a sexual partner aged 25 or older, and less likely to test
      positive for HIV and HSV-2 at follow-up compared to control groups. We examined
      the hypotheses that girls in the intervention groups had smaller age differences
      than control groups and that large age differences were associated with
      relationship-level HIV transmission risk factors: inconsistent condom use, sex
      frequency, and relationship duration. METHODS: We conducted an analysis of
      schoolgirls in the Schooling, Income, and Health Risk (SIHR) study aged 13-22 at
      baseline (n = 2907). We investigated the effects of study arm, trial stage and
      participant age on age differences in sexual relationships using a linear mixed
      effects model. Cumulative-link mixed-effects models were used to estimate the
      effect of relationship age difference on condom use and sex frequency, and a Cox
      proportional hazard model was used to estimate the effect of relationship age
      difference on relationship duration. We controlled for the girl's age, number of
      partners, study group and study round. RESULTS: Girls receiving cash transfers,
      on average, had smaller age differences in relationships compared to controls,
      though the estimated difference was not statistically significant (- 0.43 years;
      95% CI: -1.03, 0.17). The older the participant was, the smaller her age
      differences (- 0.67 per 4-year increase in age; 95% CI: -0.99, - 0.35). Among
      controls, after the cash transfers had ended the average age difference was 0.82
      years larger than during the intervention (95% CI: 0.43, 1.21), suggesting a
      possible indirect effect of the study on behaviour in the community as a whole.
      Across treatment groups, larger age differences in relationships were associated
      with lower levels of condom use, more frequent sex, and longer relationship
      durations. CONCLUSIONS: Cash-transfer programmes may prevent HIV transmission in
      part by encouraging young women to form age-similar relationships, which are
      characterised by increased condom use and reduced sex frequency. The benefits of
      these programmes may extend to those who are not directly receiving the cash.

PMID- 29587711
TI  - A review of paper-based advance care planning aids.
AB  - BACKGROUND: Advance care planning (ACP) aids can help prepare patients, family
      members, and physicians for in-the-moment medical decision-making. We wished to
      describe the content and approach of paper-based ACP aids in order to
      characterize existing aids and inform the development of a new ACP aid. METHODS:
      Paper-based ACP aids were identified through an environmental scan and screened
      for eligibility. ACP conceptual frameworks and data were gathered via stakeholder
      engagement and used to inform the coding framework that two investigators used to
      independently code each aid. A directed content analysis was conducted on these
      eligible aids. Aids were categorized through a deliberative process with an
      investigator abstracting general information for each aid. RESULTS: Fifteen aids
      met the eligibility criteria. They ranged in length from 6 to 78 pages with the
      average aid written at an eighth-grade reading level. The content analysis
      revealed that many aids encouraged choosing a surrogate decision maker and
      informed users about legal medical documents. Fewer than half of the aids
      facilitated patient clarification of values regarding quality of life issues. The
      authors identified and termed the following three categories of aids:
      informative; semi-action oriented; and action-oriented. It was often unclear
      whether patients contributed to the development or testing of the ACP aids
      reviewed. CONCLUSIONS: Most existing paper-based ACP aids address legal matters
      such as completing an advance directive. Only a minority elicited patient values
      and it was unclear whether any were developed in partnership with patients.
      Future development of ACP aids should account for patient preferences with a goal
      of supporting in-the-moment medical decision-making.

PMID- 29587712
TI  - The association between employment status and health among British adults with
      and without intellectual impairments: cross-sectional analyses of a cohort study.
AB  - BACKGROUND: There exists a well established link between employment status and
      health, with unemployment being associated with poorer health. Much less is known
      about the association between economic inactivity and health, especially among
      people with disabilities. Our aim is to determine whether the association between
      employment status and health is similar for adults with and adults without
      intellectual impairment. METHODS: Using nationally representative data from the
      1970 British Cohort Study, we undertook a series of cross sectional analyses of
      the association between employment status and health (self-reported general
      health, mental health) among British adults with and without intellectual
      impairments at ages 26, 30, 34, 38 and 42. RESULTS: People with intellectual
      disability and borderline intellectual functioning had markedly lower employment
      rates and poorer health than other participants at all waves of data collection.
      When compared with participants in full-time employment the prevalence of poorer
      self rated health and mental health was higher among participants with and
      without intellectual impairment who were in either part-time employment or were
      economically inactive at all ages. When compared with participants in employment
      the prevalence of poorer self rated health and mental health was higher among
      participants with and without intellectual impairment who were in the
      economically inactive categories of unemployment, education/training and
      ill/disabled at all ages. Intellectual disability status appeared to moderate the
      strength of the relationship between economic activity and self-rated health and,
      to a much lesser extent, the relationship between economic activity and mental
      health. In all instances the moderation indicated a stronger association among
      participants without intellectual impairment. CONCLUSIONS: The results provide
      substantive evidence to suggest that the nature of the well-established
      association between employment and better health is similar for British adults
      with and without intellectual impairments. The results do, however, indicate that
      the magnitude of the effect involved differed. Further research is needed to
      identify mechanisms that may underlie this difference.

PMID- 29587713
TI  - Identifying complications requiring re-operation following primary hip or knee
      arthroplasty: a consecutive series of 98 patients.
AB  - BACKGROUND: The number of hip and knee arthroplasties completed is expected to
      double over the next decade. In public hospitals, regular post-arthroplasty
      orthopaedic review has commonly occurred for the duration of a patient's life,
      which requires substantial outpatient resources. However, there is limited
      evidence regarding the utility of these reviews for identifying complications.
      The current study investigated when and where complications requiring re
      operation were identified following primary hip or knee arthroplasty. METHODS:
      The medical records of all patients requiring re-operation for complications
      following primary hip arthroplasty (n = 48, 2004 to 2015) or knee primary
      arthroplasty (n = 50, 1998 to 2015) at a large regional health service were
      evaluated. Data were extracted by one of four investigators using a standardised
      electronic data extraction tool. Variables of interest included the health
      setting where the complication was initially identified, how long following the
      original operation the complication was identified and whether the complication
      was symptomatic. RESULTS: Routine post-arthroplasty orthopaedic appointments
      identified 15 (15.3%) complications requiring re-operation; all were identified
      in the first-year post-surgery. For each complication identified in the first
      year post-surgery, approximately 1000 orthopaedic outpatient appointments were
      required. After the first year, all complications were identified in Emergency
      Departments (n = 30, 30.6%), General Practice (n = 24, 24.5%) or non-routine
      orthopaedic outpatient appointments (n = 19, 19.4%). All patients with
      complications reported symptoms. CONCLUSIONS: Routine post-arthroplasty review
      appointments were an inefficient mechanism for identifying complications
      requiring re-operation more than one year following surgery. Public health
      services should consider assessing and redesigning post-arthroplasty review
      services to reduce the burden on patients and the demand for outpatient
      appointments.

PMID- 29587714
TI  - Varicella in Poland: economic burden in children 1-12 years of age in Poland,
      2010-2015.
AB  - BACKGROUND: The safety and efficacy of live-attenuated varicella zoster virus
      (VZV) vaccines in preventing varicella and reducing associated morbidity and
      mortality in real-world have been previously shown. In Poland, VZV vaccination is
      only mandatory for certain high-risk individuals. Here, we have conducted an
      evaluation of the clinical and economic burden of varicella in Poland. METHODS:
      Multicenter, retrospective chart review of varicella inpatients and outpatients
      aged 1-12 years with a primary diagnosis between 2010 and 2015. Varicella-related
      outcomes included the incidence of complications, the proportion of patients
      reporting healthcare resource utilization (HCRU), and frequency of HCRU. Direct
      costs were derived from per patient resource use multiplied by unit costs, and
      indirect costs were calculated as loss of revenue of caregivers reporting work
      days missed. The overall annual cost of varicella in Poland was estimated based
      on the calculated direct and indirect costs per case and the estimated number of
      varicella cases. All costs are presented in 2015 Polish zloty (PLN) / Euros (?).
      RESULTS: A total of 150 children with varicella were included, of which 75 were
      outpatients and 75 were inpatients with a mean (+/- SD) age of 3.9 (+/-2.6) and
      4.2 (+/-2.3) years, respectively. Complications were experienced by 14.7% of
      outpatients and 82.7% of inpatients, of which the most common were skin and soft
      tissue infections and dehydration. The rate of HCRU was as follows: over-the
      counter medications (80.0% outpatients, 81.3% inpatients), prescription
      medications (80.0% outpatients, 93.3% inpatients), tests/procedures (0.0%
      outpatients, 69.3% inpatients), and allied health professional consults (0.0%
      outpatients, 24.0% inpatients). Total (direct and indirect) cost per varicella
      case was 5013.3 PLN (? 1198.1) for inpatients and 1027.2 PLN (? 245.5) for
      outpatients, resulting in an estimated overall annual (2015) cost of varicella in
      Poland of 178,198,320 PLN (? 42,588,385) among children aged 1-15 years.
      CONCLUSIONS: Significant clinical and economic burden is associated with
      varicella in Poland. These results may be used to foster discussion related to
      the implications of implementing routine VZV vaccination in Poland.

PMID- 29587715
TI  - Comparative effectiveness of school-based caries prevention: a prospective cohort
      study.
AB  - BACKGROUND: Dental caries is the world's most prevalent childhood disease. School
      based caries prevention can reduce the risk of childhood caries by increasing
      access to care. However, the optimal mix of treatment services, intensity, and
      frequency of care is unknown. METHODS: Data were derived from two prospective
      cohorts of US children participating in two caries prevention programs with
      different treatment intensities. One program provided primary and secondary
      prevention (glass ionomer sealants and interim therapeutic restorations) and one
      primary prevention only (glass ionomer sealants), both given twice yearly in six
      month intervals. Primary study outcomes included untreated decay and the total
      observed caries experience. Analysis used generalized additive models to estimate
      nonlinear effects and trends over time. Results were compared to those estimated
      using generalized estimating equations and mixed-effects multilevel Poisson
      regression. RESULTS: Primary and secondary prevention combined did not
      significantly reduce total caries experience compared to primary prevention
      alone, but did reduce the risk of untreated decay on permanent dentition.
      Additionally, the rate of new caries experience was slower in the primary and
      secondary prevention group. Nonlinear trends for dental caries across both
      programs were statistically significant from zero (p < .001). CONCLUSION: Caries
      prevention consisting of primary and secondary prevention agents may be more
      effective than primary prevention alone in reducing the risk of tooth decay over
      time. Results suggest that the impact of caries prevention may not be constant
      over the medium- and long-term, suggesting reduced effectiveness with continued
      treatments.

PMID- 29587716
TI  - Matrix metalloproteinase-8 levels in oral samples as a biomarker for
      periodontitis in the Chinese population: an observational study.
AB  - BACKGROUND: Clinical evaluation of periodontal inflammation does not fully
      reflect the disease activity. Extensive studies have been conducted out on
      gingival crevicular fluid (GCF) components that might serve as potential
      diagnostic markers for periodontitis, among which matrix metalloproteinase-8 (MMP
      8) has shown to be promising, but there were no studies for individuals in China.
      The aim of this study was to compare clinical diagnostic parameters and levels of
      active MMP-8 (aMMP-8) in GCF and oral rinse samples from the Chinese patients
      with varying degrees of periodontal inflammation. METHODS: GCF and oral rinse
      samples were obtained from 60 participants into two groups, a periodontitis group
      and a control group, specified by the presence and number of pocket depths or
      attachment loss. The aMMP-8 levels in GCF and oral rinse samples was quantified
      by ELISA using specific monoclonal antibodies. Logistic and linear regression
      models were employed for testing the correlation between aMMP-8 levels and
      periodontal condition, as well as diagnostic sensitivity and specificity.
      RESULTS: Periodontitis group (mean = 24.84 ng/ml) exhibited significantly higher
      aMMP-8 levels than control group in GCF (p < 0.001). The aMMP-8 levels in oral
      rinse samples ranged from 0.05 to 2.18 ng/ml, but differences were not
      statistically significant between the two groups (p > 0.1). Receiver operating
      characteristic curve analysis showed a highest threshold of 6.66, with a
      corresponding sensitivity and specificity of 0.8 and 0.9, respectively.
      CONCLUSIONS: Measuring aMMP-8 levels in GCF may have potentiality for
      complementary early diagnosis of periodontal disease and inflammation in the
      Chinese population.

PMID- 29587717
TI  - The prevalence of metabolic syndrome in patients receiving antipsychotics in
      Qatar: a cross sectional comparative study.
AB  - BACKGROUND: Metabolic abnormalities are common in patients maintained on
      antipsychotics. These abnormalities increase the risk of cardiovascular diseases
      and mortality in this population. The aim of this study is to assess the
      prevalence of metabolic syndrome (MetS) in subjects maintained on antipsychotics
      relative to controls in Qatar, and to assess the factors contributing to the
      development of MetS. METHODS: A cross sectional design was used to collect data
      and fasting blood samples from subjects maintained on antipsychotics for at least
      six months (n = 112) and from a control group (n = 114). The groups were compared
      in regard to prevalence of MetS, and multiple regression analysis was used to
      determine the risk factors in each group. RESULTS: The two groups (antipsychotics
      vs. control) were similar in regard to age (35.73 +/- 10.28 vs. 35.73 +/- 8.16
      years) and gender ratio. The MetS was higher among the subjects on
      antipsychotics, but this difference did not reach statistical significance. Blood
      pressure (BP) was significantly higher in the antipsychotics group and BMI was
      the major risk factor to develop MetS in this group. CONCLUSIONS: The prevalence
      of MetS in both groups is high and mostly attributed to obesity and high BP.
      Public health interventions are needed to address this major health problem
      overall. Larger studies are needed to further assess the impact of antipsychotics
      and mental illness on the development of MetS.

PMID- 29587718
TI  - Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate
      cancer patients: a multicenter, non-interventional, prospective study.
AB  - BACKGROUND: Although triptorelin is increasingly used in China for biochemical
      castration, its effects on primary prostate cancer symptoms remain unclear. This
      study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in
      Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS.
      METHODS: In this 48-week multicenter, non-interventional, prospective study, we
      enrolled patients with locally advanced or metastatic prostate cancer. Patients
      received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and
      36 with symptom assessment using the International Prostate Symptoms Score
      (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS
      categories and the percentage of patients with moderate to severe LUTS (IPSS > 7)
      at baseline, having at least a 3-point reduction of IPSS score at week 48.
      RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among
      them had severe and moderate LUTS, respectively. Of the patients with IPSS scores
      available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in
      IPSS of at least 3 points. Of the patients with moderate to severe LUTS at
      baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6%
      achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast
      majority of Chinese patients with locally advanced or metastatic prostate cancer
      scheduled to receive triptorelin as part of their standard treatment have severe
      or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS
      in these patients.

PMID- 29587719
TI  - Nurse led home-based care for people with HIV/AIDS.
AB  - BACKGROUND: Home-based care is used in many countries to increase quality of life
      and limit hospital stay, particularly where public health services are
      overburdened. Home-based care objectives for HIV/AIDS can include medical care,
      delivery of antiretroviral treatment and psychosocial support. This review
      assesses the effects of home-based nursing on morbidity in people infected with
      HIV/AIDS. METHODS: The trials studied are in HIV positive adults and children,
      regardless of sex or setting and all randomised controlled. Home-based care
      provided by qualified nurses was compared with hospital or health-facility based
      treatment. The following electronic databases were searched from January 1980 to
      March 2015: AIDSearch, CINAHL, Cochrane Register of Controlled Trials, EMBASE,
      MEDLINE and PsycINFO/LIT, with an updated search in November 2016. Two authors
      independently screened titles and abstracts from the electronic search based on
      the study design, interventions and types of participant. For all selected
      abstracts, full text articles were obtained. The final study selection was
      determined with use of an eligibility form. Data extraction was performed
      independently from assessment of risk of bias. The results were analysed by
      narrative synthesis, in order to be able to obtain relevant effect measures plus
      95% confidence intervals. RESULTS: Seven studies met the inclusion criteria. The
      trial size varied from 37 to 238 participants. Only one trial was conducted in
      children. Five studies were conducted in the USA and two in China. Four studies
      looked at home-based adherence support and the rest at providing home-based
      psychosocial support. Reported adherence to antiretroviral drugs improved with
      nurse-led home-based care but did not affect viral load. Psychiatric nurse
      support in those with existing mental health conditions improved mental health
      and depressive symptoms. Home-based psychological support impacted on HIV stigma,
      worry and physical functioning and in certain cases depressive symptoms.
      CONCLUSIONS: Nurse-led home-based interventions could help adherence to
      antiretroviral therapy and improve mental health. Further larger scale studies
      are needed, looking in more detail at improving medical care for HIV, especially
      related to screening and management of opportunistic infections and co
      morbidities.

PMID- 29587720
TI  - Spontaneous adrenocorticotropic hormone (ACTH) normalisation due to tumour
      regression induced by metyrapone in a patient with ectopic ACTH syndrome: case
      report and literature review.
AB  - BACKGROUND: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is caused
      by tumours releasing ACTH. Ectopic ACTH-producing tumour regression is rarely
      induced using steroidogenesis inhibitors. We presented a case of EAS in which
      ACTH production by a lung tumour was reduced by metyrapone (MTP) and also
      reviewed previous cases of ectopic ACTH production suppressed via steroidogenesis
      inhibition. CASE PRESENTATION: A 71-year-old female with general fatigue, central
      obesity and impaired glucose tolerance was diagnosed with Cushing's syndrome due
      to elevated ACTH (192.9 pg/mL; normal range, 7.2-63.3 pg/mL), cortisol (73.1
      MUg/dL; 6.4-21.0 MUg/dL) and 24-h urinary free cortisol (UFC) (6160 MUg/day; 11.2
      80.3 MUg/day) levels. Chest computed tomography identified a solid 26.6 * 22.9 *
      30.0 mm tumour with a cavity in the upper lobe of the left lung. There was no
      adrenal gland enlargement. Tumour markers were not significantly elevated; ACTH
      levels were not suppressed by 8-mg dexamethasone. A corticotropin-releasing
      hormone stimulation test revealed blunted ACTH response (basal ACTH, 204.6 pg/mL;
      highest ACTH level during the 120-min stimulation test, 214.0 pg/mL). She was
      diagnosed with EAS due to a lung lesion. MTP treatment was started to reduce
      cortisol production. ACTH levels and cortisol and UFC levels were normalised and
      the ACTH-producing lung tumour was ablated after MTP treatment. In several
      reported cases, plasma ACTH levels reduced during steroidogenesis inhibitor
      treatment for EAS. Among the 10 patients, three cases of pheochromocytoma, one of
      thymic carcinoid and one of islet cell carcinoma were reported. In four cases,
      the tumour was not detected. In our case, the pathology of the lung tumour was
      unknown because of lack of tumour cells in biopsy. The patients were treated with
      ketoconazole (KTZ) and/or MTP and exhibited ACTH and cortisol/UFC suppression,
      but tumour regression was observed only in our case. CONCLUSION: MTP and/or KTZ
      may reduce ACTH and cortisol production. The tumour spontaneously regressed after
      MTP treatment, indicating that MTP may reduce the tumour size without surgery.
      The mechanisms of therapeutic effects of steroidogenesis inhibitors and prognosis
      of spontaneous remission should be elucidated further via molecular biology
      studies.

PMID- 29587721
TI  - Older adults' readiness to engage with eHealth patient education and self-care
      resources: a cross-sectional survey.
AB  - BACKGROUND: This study examined access to digital technologies, skills and
      experience, and preferences for using web-based and other digital technologies to
      obtain health information and advice among older adults in a large health plan. A
      primary aim was to assess the extent to which digital divides by race/ethnicity
      and age group might affect the ability of a large percentage of seniors, and
      especially those in vulnerable groups, to engage with online health information
      and advice modalities (eHIA) and mobile health (mHealth) monitoring tools.
      METHODS: A mailed survey was conducted with age-sex stratified random samples of
      English-speaking non-Hispanic white, African-American/black (black),
      Hispanic/Latino (Latino), Filipino-American (Filipino), and Chinese-American
      (Chinese) Kaiser Permanente Northern California members who were aged 65-79
      years. Respondent data were weighted to the study population for the cross
      sectional analyses. RESULTS: Older seniors and black, Latino, and Filipino
      seniors have less access to digital tools, less experience performing a variety
      of online tasks, and are less likely to believe that they would be capable of
      going online for health information and advice compared to younger and white Non
      Hispanic seniors. Consequently, they are also less likely to be interested in
      using eHIA modalities. CONCLUSIONS: The same subgroups of seniors that have
      previously been shown to have higher prevalence of chronic conditions and greater
      difficulties with healthcare access are also less likely to adopt use of eHIA and
      mHealth monitoring technologies. At the patient population level, this digital
      divide is important to take into account when planning health information and
      chronic disease management programs. At the individual patient level, to provide
      good patient-centered care, it is important for providers to assess rather than
      assume digital access, eHealth skills, and preferences prior to recommending use
      of web-based resources and mHealth tools.

PMID- 29587722
TI  - Personality traits and career choices among physicians in Finland: employment
      sector, clinical patient contact, specialty and change of specialty.
AB  - BACKGROUND: Personality influences an individual's adaptation to a specific job
      or organization. Little is known about personality trait differences between
      medical career and specialty choices after graduating from medical school when
      actually practicing different medical specialties. Moreover, whether personality
      traits contribute to important career choices such as choosing to work in the
      private or public sector or with clinical patient contact, as well as change of
      specialty, have remained largely unexplored. In a nationally representative
      sample of Finnish physicians (N = 2837) we examined how personality traits are
      associated with medical career choices after graduating from medical school, in
      terms of employment sector, patient contact, medical specialty and change of
      specialty. METHODS: Personality was assessed using the shortened version of the
      Big Five Inventory (S-BFI). An analysis of covariance with posthoc tests for
      pairwise comparisons was conducted, adjusted for gender and age with confounders
      (employment sector, clinical patient contact and medical specialty). RESULTS:
      Higher openness was associated with working in the private sector, specializing
      in psychiatry, changing specialty and not practicing with patients. Lower
      openness was associated with a high amount of patient contact and specializing in
      general practice as well as ophthalmology and otorhinolaryngology. Higher
      conscientiousness was associated with a high amount of patient contact and
      specializing in surgery and other internal medicine specialties. Lower
      conscientiousness was associated with specializing in psychiatry and hospital
      service specialties. Higher agreeableness was associated with working in the
      private sector and specializing in general practice and occupational health.
      Lower agreeableness and neuroticism were associated with specializing in surgery.
      Higher extraversion was associated with specializing in pediatrics and change of
      specialty. Lower extraversion was associated with not practicing with patients.
      CONCLUSIONS: The results showed distinctive personality traits to be associated
      with physicians' career and specialty choices after medical school independent of
      known confounding factors. Openness was the most consistent personality trait
      associated with physicians' career choices in terms of employment sector, amount
      of clinical patient contact, specialty choice and change of specialty.
      Personality-conscious medical career counseling and career guidance during and
      after medical education might enhance the person-job fit among physicians.

PMID- 29587723
TI  - Patient satisfaction and gender composition of physicians - a cross-sectional
      study of community health services in Hubei, China.
AB  - BACKGROUND: Patient satisfaction is associated with both individual (patients and
      health workers) and organizational (health facilities) characteristics. This
      study aimed to establish a link between patient satisfaction and gender
      composition of physicians in community health service (CHS) organizations.
      METHODS: Participants were selected through multistage stratified random
      sampling: 36 CHS centers were selected from six municipalities in Hubei, China.
      All physicians on duty and patients visiting the CHS during the study period
      (from April to October in 2015) were invited to participate in this study: 324
      physicians and 865 patients completed a questionnaire survey. Multilevel linear
      regression analyses were performed to determine the associations of patient
      satisfaction (scored from 1 to 5) with patient characteristics (gender, age,
      education, income, medical expense, frequency of visits to the CHS) and
      organizational features of the CHS (sex ratio of physicians, and gender
      differences of physicians in education and job satisfaction). RESULTS: Older
      patients and those with a higher medical bill had a lower degree of satisfaction
      (p < 0.05). At the organizational level: a higher proportion of male physicians
      weakened the negative association between patient age and patient satisfaction (p
      < 0.05); a larger gap in university qualifications between male and female
      physicians exacerbated the negative association between patient age and patient
      satisfaction (p < 0.05). CONCLUSIONS: The gender composition of physicians in
      CHSs is associated with patient satisfaction in the Chinese context: a larger gap
      (in number and qualifications) between male and female physicians is associated
      with higher patient satisfaction. Further studies are needed to explore the
      cultural roots of such an association.

PMID- 29587724
TI  - Prevalence and correlates of depression and alcohol use disorder among adults
      attending primary health care services in Nepal: a cross sectional study.
AB  - BACKGROUND: Although depression and alcohol use disorder (AUD) are expected to be
      common among patients presenting to primary health care setting, there is limited
      research on prevalence of depression and AUD among people attending primary
      health care services in low-income countries. The aim of this study was to assess
      the prevalence of depression and AUD among adults attending primary care
      facilities in Nepal and explore factors associated with depression and AUD.
      METHODS: We conducted a population-based cross-sectional health facility survey
      with 1474 adults attending 10 primary healthcare facilities in Chitwan district,
      Nepal. The prevalence of depression and AUD was assessed with validated Nepali
      versions of the Patient Health Questionnaire (PHQ-9) and Alcohol Use Disorder
      Identification Test (AUDIT). RESULTS: 16.8% of the study sample (females 19.6%
      and males 11.3%) met the threshold for depression and 7.3% (males 19.8% and
      females 1.1%) for AUD. The rates of depression was higher among females (RR =
      1.48, P = 0.009), whereas rates of AUD was lower among females (RR = 0.49, P =
      0.000). Rates of depression and AUD varied based on education, caste/ethnicity,
      occupations and family income. CONCLUSIONS: In Nepal, one out of five women
      attending primary care services have depression and one out of five men have AUD.
      Primary care settings, therefore, are an important setting for detection and
      treatment initiation for these conditions. Given that "other" occupation is at
      increased risk for both conditions, it will be important to assure that
      treatments are feasible and effective for this high risk group.

PMID- 29587725
TI  - Associations between emotional intelligence, empathy and personality in Japanese
      medical students.
AB  - BACKGROUND: It is known that empathic communication is important for physicians
      to achieve higher patient satisfaction and health outcomes. Emotional
      intelligence (EI), empathy and personality in medical students predict students'
      individual disposition and their emotional and empathic perceptions. This study
      aimed to investigate: 1) The association between empathy, EI and personality, and
      2) Gender differences in the association between empathy, EI and personality.
      METHOD: Participants were 357 1st year medical students from 2008 to 2011 at one
      medical school in Japan. Students completed self-report questionnaires comprising
      three validated instruments measuring EI: Trait Emotional Intelligence
      Questionnaire-Short Form (TEIQue-SF), empathy: Jefferson Scale of Physician
      Empathy- student version (JSPE) and personality: NEO-Five-Factor Inventory (NEO
      FFI), which explores 5 dimensions of personality Neuroticism (N), Extraversion
      (E), Openness to experience (O), Agreeableness (A), and Conscientiousness (C).
      RESULTS: Pearson Correlations showed weak association between TEIQue-SF and JSPE.
      TEIQue-SF and NEO-FFI showed positive correlation for E and C, and strong
      negative correlation for N and weak positive correlation for A and O. Weak
      positive correlation between JSPE and the NEO-FFI were observed for E and A.
      Although effect sizes were small, N, A and empathy were significantly higher in
      females (unpaired t-test). However, hierarchical multiple-regression analysis
      when controlling for gender and personality showed no association between EI,
      empathy and gender. A, TEIQue-SF and N were found to make small contributions in
      respect of predictions for JSPE. Personality contributed significantly to the
      prediction of TEIQue-SF. N had the largest independent negative contribution
      (beta = - 0,38). CONCLUSION: In our study population of 1st year medical
      students, females had significantly higher N, A and empathy scores than males.
      Medical students' N score was strongly negatively associated with EI. Empathy was
      weakly associated with EI and A. However, when controlling gender and personality
      in regression analysis, gender did not affect EI and empathy, rather personality
      is the most important factor. Our findings indicate that N is a major factor that
      negatively affects EI. It is important to mitigate N using thoughtful training,
      taking into account students' personalities, to reduce N. In future studies, we
      will assess how communication trainings for students might enhance EI.

PMID- 29587726
TI  - Perceptions, experiences and expectations of Iraqi medical students.
AB  - BACKGROUND: The environment for medical education in Iraq has been difficult for
      many years. The 2003 invasion of Iraq accelerated a steady emigration of faculty
      and graduates. Kidnappings and deaths of doctors became commonplace. To
      understand current career plans, expectations and perceptions of medical
      students, three Baghdad medical schools were surveyed. METHODS: Written
      questionnaires were completed by 418 medical students variously in their 4th, 5th
      and 6th (final)years of training. We asked about perceptions of the quality of
      their medical education, the quality of health services in Iraq generally, and
      about deaths, injuries and migration of faculty, classmates and family. RESULTS:
      The average age of students was 22 years, with 59% women. Most students (90%)
      were originally from Baghdad. Although there were some positive responses, many
      students (59%) rated the overall quality of their medical education as fair or
      poor. Three-fourths of students believed the quality of hospital care in Iraq to
      be only fair or poor. A majority of students (57%) stated they were thinking
      frequently or all the time about leaving Iraq after graduation. Reasons given for
      leaving included the desire for further education, seeking a better lifestyle and
      fleeing conflict. Leading reasons for staying included the pull of friends and
      family, familiarity with the health system, and a sense of responsibility to the
      country. Nearly one in five (18%) students reported the death of a family member
      attributable to intentional violence, and 15% reported the violent death of a
      medical school classmate or faculty member since the 2003 invasion. Half the
      students reported at least one school faculty members had left Iraq because of
      the war. CONCLUSION: Medical students hold a mediocre view of the quality of
      their medical education and of Iraq's health system. Many of their faculty
      members have left the country. The majority of students may leave Iraq after
      graduation, afforded the opportunity. This poses a significant problem for
      staffing an already demoralized and stressed health system. Current circumstances
      suggest the situation will continue to deteriorate.

PMID- 29587727
TI  - Assessing youth-friendly sexual and reproductive health services: a systematic
      review.
AB  - BACKGROUND: Over the last quarter century, there has been an emergence of
      evidence-based research directed toward the development, implementation, and
      assessment of youth-friendly health services (YFHS) to improve the delivery of
      sexual and reproductive health services for young people. Despite these research
      efforts, evidence supporting the effectiveness of YFHS is limited, which may be
      attributed to a lack of consensus on how to define and measure youth-friendliness
      to track progress and evaluate outcomes. The purpose of this systematic review is
      to assess how youth-friendly sexual and reproductive health services are measured
      worldwide. METHODS: We conducted a systematic review of studies measuring youth
      friendly sexual and reproductive health services at health facilities published
      between January 2000 and June 2015 using PubMed, Web of Science, and POPLINE
      databases. Additional studies were identified by reviewing references of selected
      articles. Studies were screened to identify measurements and indicators that have
      been used to measure YFHS. RESULTS: Our review identified 20 studies from an
      initial search of more than 11,000 records, including six from high-income
      countries and 14 from low-and middle-income countries. The review identified 115
      indicators used for measuring youth-friendly sexual and reproductive health
      services. Our review found a lack of consistency in the tools and indicators used
      to measure YFHS. The three most frequently assessed domains were accessibility,
      staff characteristics and competency, and confidentiality and privacy. The
      majority of the indicators were not specific to young people's needs and often
      reflected basic standards of care. CONCLUSIONS: This review shows the need for
      standardization and prioritization of indicators for the evaluation of YFHS. The
      results can be used to identify a core set of indicators that can be incorporated
      into a framework for assessing youth-friendly sexual and reproductive health
      services. There is a need to further distinguish between those variables that may
      have greatest impact on the use of services by young people, such as respect and
      privacy, those that impact the quality of services offered, and those that have
      limited relevance. Conducting more rigorous studies using a refined set of
      indicators is critical to measure and compare the impact and effectiveness of
      YFHS efforts.

PMID- 29587728
TI  - Anatomical landmarks of the intra-pelvic side-wall as sources of pain in women
      with and without pregnancy-related chronic pelvic pain after childbirth: a
      descriptive study.
AB  - BACKGROUND: Chronic pelvic pain (CPP) affects 15-24% of women and can have a
      devastating impact on quality of life. Laparoscopy is often used in the
      investigation, although in one third of the examinations there is no visible
      pathology and the women may be dismissed without further investigation. Also, the
      contribution of skeletal, muscular, periosteal and ligamentous tissues to CPP
      remains to be further elucidated. The objective of the present study was to
      compare pain intensity provoked from anatomical landmarks of the intra-pelvic
      side-wall in women with pregnancy-related CPP after childbirth and women without
      such pain. METHODS: This is a descriptive study of 36 non-randomly selected
      parous women with CPP after childbirth and 29 likewise selected parous women
      after childbirth without CPP. Pain was determined by questionnaire and clinical
      examination. The primary outcome measure was reported pain intensity provoked on
      13 anatomical landmarks of the intra-pelvic side-wall. All women reported their
      perceived pain intensity for each anatomical landmark on Likert scales and an
      individual sum score was calculated. RESULTS: Women with chronic pelvic pain were
      older than women without CPP. At several intra-pelvic landmarks high intensity
      pain was provoked in women with CPP compared with less intense pain provoked at
      fewer landmarks in women without low back or pelvic pain (p < 0.0001). The
      average sum of pain intensity scores was about 4 times higher in women with CPP
      (1.3) as compared with those without low back or pelvic pain (0.3), p < 0.0001.
      This association remained when adjusting for the age difference between the pain
      groups in linear regression analysis. In addition, reported pain intensity at
      worst past week was independently associated with sum of pain intensity scores.
      The maximum individual sum of pain intensity scores among women without CPP was
      exceeded by that of 85% of the women with CPP. CONCLUSIONS: Parous women with CPP
      after childbirth had a heightened pain intensity over 13 anatomical landmarks
      during pelvic examination compared with parous women without CPP. These results
      need to be confirmed in a larger cohort with different types of CPP.

PMID- 29587729
TI  - Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal
      root ganglion with conventional medical management (CMM) in patients with chronic
      post-surgical inguinal pain: the SMASHING trial.
AB  - BACKGROUND: A significant number of patients who undergo a standard inguinal
      hernia repair or a Pfannenstiel incision develop chronic (> 3 months) post
      surgical inguinal pain (PSIP) due to nerve entrapment. If medication or
      peripheral nerve blocks fail, surgery including neurectomies may offer relief.
      However, some patients do not respond to any of the currently available remedial
      treatment modalities. Targeted spinal cord stimulation (SCS) of the dorsal root
      ganglion (DRG) is a relatively new type of therapy that has a potential to
      significantly reduce chronic PSIP. The Axium(r) SCS System (Spinal Modulation
      Inc., NY, USA) has been shown to be safe and successful in small cohorts of PSIP
      patients. Aim of this study is to evaluate targeted spinal cord stimulation
      therapy in patients with PSIP. METHODS: A prospective, multicentre, randomized
      controlled trial with optional one-way crossover will assess the efficacy of the
      Axium(r) SCS system for the treatment of PSIP. Seventy-eight patients with
      intractable PSIP following open hernia repair or Pfannenstiel incision who did
      not respond favorably to previous pain treatment regimens including a neurectomy
      will be randomized to either an Axium(r) SCS arm or a control arm receiving only
      conventional medical management (CMM). Primary outcome is the difference in
      percentage of subjects with >=50% pain relief after 6 months using a Numerical
      Pain Rating Scale (NPRS). Data are collected using a daily pain/sleep diary and a
      number needed to treat (NNT) analysis is performed. Various secondary outcomes
      will be collected. DISCUSSION: Targeted SCS stimulation of the DRG using the
      Axium(r) SCS system will possibly offer significant pain reduction in patients
      with PSIP who are refractory to other treatment modalities. TRIAL REGISTRATION:
      The study protocol is registered at the NIH Clinical Trials Registry (
      http://clinicaltrials.gov , ClinicalTrials.gov identifier: NCT02349659 ) on
      January 29, 2015.

PMID- 29587730
TI  - Applying interprofessional Team-Based Learning in patient safety: a pilot
      evaluation study.
AB  - BACKGROUND: Interprofessional education (IPE) interventions are not always
      successful in achieving learning outcomes. Team-Based Learning (TBL) would appear
      to be a suitable pedagogical method for IPE, as it focuses on team performance;
      however, little is known about interprofessional TBL as an instructional
      framework for patient safety. In this pilot-study, we aimed to (1) describe
      participants' reactions to TBL, (2) observe their achievement with respect to
      interprofessional education learning objectives, and (3) document their
      attitudinal shifts with regard to patient safety behaviours. METHODS: We
      developed and implemented a three-day course for pre-qualifying, non-medical
      healthcare students to give instruction on non-technical skills related to
      'learning from errors'. The course consisted of three sequential modules:
      'Recognizing Errors', 'Analysing Errors', and 'Reporting Errors'. The evaluation
      took place within a quasi-experimental pre-test-post-test study design.
      Participants completed self-assessments through valid and reliable instruments
      such as the Mennenga's TBL Student Assessment Instrument and the University of
      the West of England's Interprofessional Questionnaire. The mean scores of the
      individual readiness assurance tests were compared with the scores of the group
      readiness assurance test in order to explore if students learned from each other
      during group discussions. Data was analysed using descriptive (i.e. mean,
      standard deviation), parametric (i.e. paired t-test), and non-parametric (i.e.
      Wilcoxon signed-rank test) methods. RESULTS: Thirty-nine students from five
      different bachelor's programs attended the course. The participants positively
      rated TBL as an instructional approach. All teams outperformed the mean score of
      their individual members during the readiness assurance process. We observed
      significant improvements in 'communication and teamwork' and 'interprofessional
      learning' but not in 'interprofessional interaction' and 'interprofessional
      relationships.' Findings on safety attitudes and behaviours were mixed.
      CONCLUSION: TBL was well received by the students. Our first findings indicate
      that interprofessional TBL seems to be a promising pedagogical method to achieve
      patient safety learning objectives. It is crucial to develop relevant clinical
      cases that involve all professions. Further research with larger sample sizes
      (e.g. including medical students) and more rigorous study designs (e.g. pre-test
      post-test with a control group) is needed to confirm our preliminary findings.

PMID- 29587731
TI  - Highly water pressurized brown rice improves cognitive dysfunction in senescence
      accelerated mouse prone 8 and reduces amyloid beta in the brain.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and the
      number of AD patients continues to increase worldwide. Components of the germ
      layer and bran of Brown rice (BR) help maintain good health and prevent AD.
      Because the germ layer and bran absorb little water and are very hard and
      difficult to cook, they are often removed during processing. To solve these
      problems, in this study, we tried to use a high-pressure (HP) technique. METHODS:
      We produced the highly water pressurized brown rice (HPBR) by pressurizing BR at
      600 MPa, and then we fed it to an AD mouse model, senescence-accelerated mouse
      prone 8, to investigate the therapeutic effects of HPBR on cognitive dysfunction
      by Y-maze spatial memory test. RESULTS: HP treatment increased the water
      absorbency of BR without nutrient loss. HPBR ameliorated cognitive dysfunction
      and reduced the levels of amyloid-beta, which is a major protein responsible for
      AD, in the brain. CONCLUSIONS: These results suggest that HPBR is effective for
      preventing AD.

PMID- 29587732
TI  - Influence of Japan's 2004 postgraduate training on ophthalmologist location
      choice, supply and distribution.
AB  - BACKGROUND: Highly-competent patient care is paramount to medicine. Quality
      training and patient accessibility to physicians with a wide range of
      specializations is essential. Yet, poor quality of life for physicians cannot be
      ignored, being detrimental to patient care and leading to personnel leaving the
      medical profession. In 2004, the Japanese government reformed postgraduate
      training for medical graduates, adding a 2-year, hands-on rotation through
      different specialties before the specialization residency was begun. Residents
      could now choose practice location, but it sparked concerns that physician
      distribution disparities had been created. Japanese media reported that residents
      were choosing specialties deemed to offer a higher quality of life, like
      Ophthalmology or Dermatology, over underserved areas like Obstetrics or
      Cardiology. To explore the consequences of Japan's policy efforts, through the
      residency reform in 2004, to improve physician training, analyzing
      ophthalmologist supply and distribution in the context of providing the best
      possible patient care and access while maintaining physician quality of life.
      METHODS: Using secondary data, we analyzed changes in ophthalmologist supply at
      the secondary tier of medical care (STM). We applied ordinary least-squares
      regression models to ophthalmologist density to reflect community factors such as
      residential quality and access to further professional development, to serve as
      predictors of ophthalmologist supply. Coefficient equality tests examined
      predictor differences before and after 2004. Similar analyses were conducted for
      all physicians excluding ophthalmologists (other physicians). Ophthalmologist
      coverage in top and bottom 10% of STMs revealed supply inequalities. RESULTS:
      Change in ophthalmologist supply was inversely associated with baseline
      ophthalmologist density before (P < .01) and after (P = .01) 2004. Changes in
      other physician supply were not associated with baseline other physician density
      before 2004 (P = 0.5), but positively associated after 2004 (P < .01).
      Inequalities between top and bottom 10% of ophthalmologist supply in STMs were
      large, with best-served areas maintaining roughly five times greater coverage
      than least-served areas. However, inequalities gradually declined between 1998
      and 2012. CONCLUSIONS: Ophthalmologist supply increased both before and after the
      2004 reform, yet contrary to media reports, proceeded at a lesser rate than
      supply increases for other physicians. After 2004, geographical disparities
      decreased for ophthalmologists, while increasing for other physicians.

PMID- 29587733
TI  - Culture of mesenchymal stem cells derived from equine synovial membrane in
      alginate hydrogel microcapsules.

PMID- 29587734
TI  - South African medicinal plant extracts active against influenza A virus.
AB  - BACKGROUND: Influenza infection remains a major health threat for animals and
      humans which crucially requires effective antiviral remedies. The usage of herbal
      medications as readily available alternatives for their compatibility with the
      body and fewer side effects compared to synthetic chemical treatments has become
      popular globally. The aim of this study was to investigate and screen in vitro
      anti-influenza activity of extracts of five South African medicinal plants,
      namely Tabernaemontana ventricosa, Cussonia spicata, Rapanea melanophloeos,
      Pittosporum viridiflorum and Clerodendrum glabrum, species which are used
      traditionally for the treatment of several diseases such as inflammatory and
      respiratory diseases. METHODS: Methanol, ethanol (100% and 30%), acetone, hot and
      cold water extracts of the powdered plants leaves were obtained by standard
      methods. The cytotoxicity was determined by the MTT colorimetric assay on MDCK
      cells. The concentrations below CC50 values were tested for antiviral activity
      against influenza A virus (IAV) in different combination treatments. The effect
      of extracts on viral surface glycoproteins and viral titer were tested by HI and
      HA virological assays, respectively. RESULTS: Based on the applied methods, the
      most effective results against IAV were obtained from Rapanea melanophloeos
      methanol leaf extract (EC50 = 113.3 MUg/ml) and Pittosporum viridiflorum
      methanol, 100% and 30% ethanol and acetone leaf extracts (EC50 values = 3.6, 3.4,
      19.2, 82.3 MUg/ml, respectively) in all types of combined treatments especially
      in pre- and post-penetration combined treatments with highly significant effects
      against viral titer (P <= 0.01). CONCLUSION: The outcomes offer for the first
      time a scientific basis for the use of extracts of Rapanea melanophloeos and
      Pittosporum viridiflorum against IAV. It is worth focusing on the isolation and
      identification of effective active compounds and elucidating the mechanism of
      action from these species. However, Tabernaemontana ventricosa, Cussonia spicata
      and Clerodendrum glabrum leaf extracts were ineffective in vitro in this study.

PMID- 29587735
TI  - Correction to: Strengthening medical training programmes by focusing on
      professional transitions: a national bridging programme to prepare medical school
      graduates for their role as medical interns in Botswana.
AB  - CORRECTION: Forllowing publication of the original article [1], the first author
      reported that there was a typographical error in the name of one of his co
      authors. The correct spelling is Alemayehu Bedada, not Alemayhu Bedada.

PMID- 29587736
TI  - Comparison of clinicopathologic characteristics, epigenetic biomarkers and
      prognosis between renal pelvic and ureteral tumors in upper tract urothelial
      carcinoma.
AB  - BACKGROUND: There's no consensus about the difference between renal pelvic and
      ureteral tumors in terms of clinical features, pathological outcomes, epigenetic
      biomarkers and prognosis. METHODS: The data of 341 patients with renal pelvic
      tumors and 271 patients with ureteral tumors who underwent radical
      nephroureterectomy between 1999 and 2011 were retrospectively reviewed. The
      clinicopathologic features, gene promoters methylation status and oncologic
      outcomes were compared. Regression analysis was performed to identify oncologic
      prognosticators. RESULTS: Patients with ureteral tumors were relatively older (p
      = 0.002), and had higher likelihood of pre-operative renal insufficiency (p <
      0.001), hypertension (p = 0.038) and hydronephrosis (P < 0.001), while in
      patients with renal pelvic tumors gross hematuria was more prevalent (p < 0.001).
      Renal pelvic tumors tended to exhibit non-organ-confined disease (p = 0.004) and
      larger tumor diameter (p = 0.001), while ureteral tumors had a higher likelihood
      of exhibiting high grade (p < 0.001) and sessile architecture (p = 0.023).
      Hypermethylated gene promoters were significantly more prevalent in renal pelvic
      tumors (p < 0.001), specifically for TMEFF2, GDF15, RASSF1A, SALL3 and ABCC6 (all
      p < 0.05). Tumor location failed to independently predict cancer-specific
      survival, overall survival, intravesical or contralateral recurrence (all p >
      0.05), while gene methylation status was demonstrated to be an independent
      prognostic factor. CONCLUSION: Renal pelvic tumors and ureteral tumors exhibited
      significant differences in clinicopathologic characteristics and epigenetic
      biomarkers. Gene promoter methylation might be an important mechanism in
      explaining distinct tumor patterns and behaviors in UTUC.

PMID- 29587737
TI  - Resident burnout: evaluating the role of the learning environment.
AB  - BACKGROUND: Although burnout is viewed as a syndrome rooted in the working
      environment and organizational culture, the role of the learning environment in
      the development of resident burnout remains unclear. We aimed to evaluate the
      association between burnout and the learning environment in a cohort of Belgian
      residents. METHODS: We conducted a cross-sectional online survey among residents
      in a large university hospital in Belgium. We used the Dutch version of the
      Maslach Burnout Inventory (UBOS-C) to assess burnout and the Dutch Residency
      Educational Climate Test (D-RECT) to assess the learning environment. RESULTS: A
      total of 236 residents (29 specialties) completed the survey (response rate
      34.6%), of which 98 (41.5%) met standard criteria for burnout. After multivariate
      regression analysis adjusting for hours worked per week, quality of life and
      satisfaction with work-life balance, we found an inverse association between D
      RECT scores and the risk of burnout (adjusted odds ratio; 0.47 for each point
      increase in D-RECT score; 95% CI, 0.23 - 0.95; p = 0.01). CONCLUSIONS: Resident
      burnout is highly prevalent in our cohort of Belgian residents. Our results
      suggest that the learning environment plays an important role in reducing the
      risk of burnout among residents.

PMID- 29587738
TI  - The relationship between long working hours and depression among first-year
      residents in Japan.
AB  - BACKGROUND: In Japan, some residents develop mental health problems. In previous
      studies, it was reported that long working hours might be a cause of stress
      reaction such as depression. There were some reports that compared residents with
      80 or more working hours with those with less than 80 working hours. However,
      many residents are practically detained for extra-long time, designated as 100 h
      or more per week, for medical practice, training, self-study, etc. There have
      been few reports on extra-long hours of work. This study evaluated the working
      environment and the amount of stress experienced by first-year residents, and
      examined the relationship between long working hours and depression, especially
      in the group of extra-long working hours. METHODS: The study included 1241 first
      year residents employed at 250 training hospitals in 2011. A self-report
      questionnaire was administered at the beginning of the residency and 3 months
      later to collect data on demographics, depressive symptoms, and training
      conditions (e.g., duration of work, sleep, disposable time, and night shift).
      Depressive symptoms were rated using the Center for Epidemiologic Studies
      Depression Scale. RESULTS: The mean duration of work per week was 79.4 h, with 97
      residents (7.8%) working 100 h or more. At 3 months, clinically significant
      depressive symptoms were reported by 45.5% of residents working 100 or more h per
      week, which proportion was significantly greater than that for respondents
      working less than 60 h (P < 0.001). Multivariate logistic regression analysis
      showed that a working week of 80 to 99.9 h was associated with a 2.83 fold higher
      risk and 100 h or more was associated with a 6.96-fold higher risk of developing
      depressive symptoms compared with a working week of less than 60 h. CONCLUSION:
      Working excessively long hours was significantly associated with development of
      depressive symptoms. Proper management of resident physicians' working hours is
      critical to maintaining their physical and mental health and to improve the
      quality of care they provide.

PMID- 29587739
TI  - Prevalence and antimicrobial susceptibility of asymptomatic bacteriuria among
      women with pelvic organ prolapse in Abakaliki, South-East Nigeria.
AB  - BACKGROUND: Pelvic organ prolapse (POP) is the herniation of pelvic organs from
      its anatomical confines, and it is of considerable importance to the practicing
      gynaecologist in middle and low income countries. It is commonly associated with,
      urinary tract infection (UTI), both symptomatic and asymptomatic due to
      anatomical and physiological changes. The aim of this study was to determine the
      prevalence of asymptomatic bacteriuria among women with pelvic organ prolapse, to
      know the organisms commonly implicated and the sensitivity pattern. METHODS: This
      study was conducted among 96 women with POP at the National Obstetric Fistula
      Centre Abakaliki. A cross sectional descriptive study was done. Standard
      microbial technique was used to analyze the urine. Data was analysed using the
      Statistical Package for Social Sciences version 17. RESULTS: Out of the 96
      patients, 76 were found to have asymptomatic bacteriuria giving a prevalence of
      79.2%. Nine different bacteria species isolated include E. Coli (34.2%),
      Streptococcus pneumonia (23.7%), Staphylococcus aureus (7.9%), Proteus Spp (7.9%)
      others (5.3%). The highest level of microbial sensitivity to the antimicrobials
      was with Ciprofloxacin. CONCLUSIONS: This study suggests that prevalence of
      asymptomatic bacteriuria is very high among women with POP. More than 50% of the
      bacterial isolates were mainly E.coli and Streptococcus pneumonia. The highest
      level of microbial sensitivity was with ciprofloxacin while the least was with
      cotrimoxazole.

PMID- 29587740
TI  - A communication-focused curriculum for dental students - an experiential training
      approach.
AB  - BACKGROUND: Successful interaction and communication with patients is as vital
      for dentists as it is for physicians. Therefore, the aim of this study was the
      development and evaluation of an interactive, experiential training curriculum
      with an emphasis on communication for dual degree seekers of medicine and
      dentistry. METHODS: A pre-clinical course with an emphasis in physician/dentist
      patient communication and interaction was adapted by a team of subject experts
      based largely on the propositions of Experiential Learning Theory. After
      attending the course, dental students (N = 81) rated the course on a Likert-
      style scale and answered two open questions. RESULTS: Students found the
      interactive course curriculum to be very helpful and vital. Many students
      reported that their initial interest in the course was mainly because it is a
      dual degree requirement, but later on rated the course as highly important in
      terms of later physician/dentist-patient interaction. One aspect of the
      curriculum course participants regarded as very important, yet neglected during
      dental studies, was (self-) perception. CONCLUSION: In the view of dental
      students, the rigorous structure of the pre-clinical dental curriculum does not
      allow for time spent on topics such as (self-) perception and awareness, but
      training one's ability to self-reflect and think critically about one's own
      actions, conduct or position can aid with advanced medical and dental studies and
      practices later on. Experiential courses with an emphasis on patient
      physician/dentist communication should be offered early on during pre-clinical
      medical and dental studies as a regular part of the curriculum.

PMID- 29587741
TI  - Isolation, molecular characterization and sero-prevalence study of foot-and-mouth
      disease virus circulating in central Ethiopia.
AB  - BACKGROUND: Ethiopian livestock production and productivity is still very low due
      to widespread of diseases. Among the diseases, foot-and-mouth disease (FMD) is an
      extremely contagious and acute viral disease that causes significant economic
      problems in the country. A cross sectional study design was conducted from
      September 2015 to May 2016 to isolate and characterize FMD virus from outbreak
      cases; determine the sero-prevalence of antibodies against FMD virus (FMDV), and
      assess potential risk factors associated with sero-prevalence of the disease in
      selected areas of central Ethiopia. A multistage sampling technique was employed
      to select the study animals. Isolated viruses were characterized by antigen ELISA
      (IZLER, Brescia, Italy) and by genetic analysis of the sequence of the viral
      protein 1 (VP1). Sero-prevalence was determined using an ELISA for antibodies
      against non-structural proteins of FMDV based on the 3ABC proteins (ID Screen(r)
      FMD NSP Competition, ID-VET, Grabels, France). Risk factors for sero-prevalence
      of antibodies against FMD virus was investigated using logistic regression
      analysis. RESULT: From outbreak investigation, 28.8% (n = 378) cattle showed
      signs and lesions suggestive of FMD and 34 samples were subjected to virus
      isolation. Twenty eight of these cultures exhibited cytopathic effect (CPE) and
      were serotyped as O, A and SAT 2 FMD viruses. One A and two SAT 2 isolates named
      A-ETH-19-2015, SAT 2-ETH-18-2015 and SAT 2-ETH-20-2015 were further characterized
      by phylogenetic analysis. The overall sero-prevalence of antibodies against non
      structural proteins of FMDV was 24.2% (n = 574). Cattle herds with crossbreed
      cattle, with older cattle (> 2 years), and kept together with small ruminants had
      higher sero-prevalences of antibodies against FMDV (p < 0.05). CONCLUSION: This
      study showed that FMD was present in the study areas. Among the associated risk
      factors, breed, age and herd composition were significantly associated with
      presence of antibodies against FMD virus. Three different serotypes (A, O and SAT
      2) were responsible for the outbreaks of the disease. Genetic analysis indicated
      that the isolated viruses clustered differently from previous outbreaks. Thus,
      further molecular analyses coupled with protection potential of the existing
      vaccines against the isolates should be performed.

PMID- 29587742
TI  - Availability, use, and affordability of medicines in urban China under universal
      health coverage: an empirical study in Hangzhou and Baoji.
AB  - BACKGROUND: This study aimed to examine the availability, use, and affordability
      of medicines in urban China following the 2009 Health Care System Reform that
      included implementation of universal health coverage (UHC). METHODS: This
      longitudinal study was performed in Hangzhou (high income, eastern China) and
      Baoji (lower income, western China). Five yearly household surveys were conducted
      (one each year from 2009 to 2013) to evaluate the impact of UHC on medicines use
      and expenditure, and a health facility survey was conducted in 2013 to evaluate
      availability of medicines. A cohort of over 800 households in Hangzhou and Baoji
      was established in 2009, and 20 hospitals were included in the health facility
      survey. Medicines use was determined using data from health facility and
      household surveys. An average, two-week out-of-pocket medicines expenditure was
      calculated to assess the affordability of medicines. RESULTS: The number of
      medicines stocked in primary health facilities in Hangzhou decreased, while the
      number in Baoji increased. In Baoji, patients usually chose a pharmacy to buy
      medicines directly, despite the 48.2% increased availability of essential
      medicines in primary health care centers. The majority of survey respondents
      stated that their medicines need was basically met; however, medicines cost still
      accounted for a major part of their health expenditure. Medicines expenditure
      showed an increasing trend from 2009 to 2013. The average annual growth rate of
      household overall medical expenditure was significantly higher than that for
      household non-food consumption expenditure. CONCLUSIONS: Following China's Health
      Care System Reform and implementation of UHC, availability and use of medicines
      has improved in urban areas. However, the affordability of medicines is still a
      concern.

PMID- 29587743
TI  - Proteomic analysis of antimicrobial effects of pegylated silver coated carbon
      nanotubes in Salmonella enterica serovar Typhimurium.
AB  - BACKGROUND: Synthesis of silver nano-compounds with enhanced antimicrobial
      effects is of great interest for the development of new antibacterial agents.
      Previous studies have reported the antibacterial properties of pegylated silver
      coated carbon nanotubes (pSWCNT-Ag) showing less toxicity in human cell lines.
      However, the mechanism underlining the pSWCNT-Ag as a bactericidal agent remained
      unfolded. Here we assessed the pSWCNT-Ag effects against foodborne pathogenic
      bacteria growth and proteome profile changes. RESULTS: Measurements of
      bioluminescent imaging, optical density, and bacteria colony forming units
      revealed dose-dependent and stronger bactericidal activity of pSWCNT-Ag than
      their non-pegylated counterparts (SWCNT-Ag). In ovo administration of pSWCNT-Ag
      or phosphate-buffered saline resulted in comparable chicken embryo development
      and growth. The proteomic analysis, using two-dimensional electrophoresis
      combined with matrix assisted laser desorption/ionization time of flight/time of
      flight mass spectrometry, was performed on control and surviving Salmonella
      enterica serovar Typhimurium to pSWCNT-Ag. A total of 15 proteins (ten up
      regulated and five down-regulated) differentially expressed proteins were
      identified. Functional analyses showed significant reduction of proteins
      associated with biofilm formation, nutrient and energy metabolism, quorum sensing
      and maintenance of cell structure and cell motility in surviving S. Typhimurium.
      In contrast, proteins associated with oxygen stress, DNA protection, starvation,
      membrane rebuilding, and alternative nutrient formation were induced as the
      compensatory reaction. CONCLUSIONS: This study provides further evidence of the
      antibacterial effects of pSWCNT-Ag nanocomposites and knowledge of their
      mechanism of action through various protein changes. The findings may lead to the
      development of more effective and safe antimicrobial agents.

PMID- 29587744
TI  - Safety and efficacy of the mesenchymal stem cell in feline eosinophilic keratitis
      treatment.
AB  - BACKGROUND: Feline eosinophilic keratitis (FEK) is a chronic keratopathy caused
      by a suspected immune mediated response to an unknown antigenic stimulus. The
      purpose of this study was to investigate the safety and therapeutic effects of
      allogeneic feline adipose-derived mesenchymal stromal cells (fAd-MSCs) implanted
      subconjunctival around the ocular surface lesion in five cats with FEK refractory
      to current available treatments. RESULTS: FEK was diagnosed by clinical
      appearance and evidence of eosinophil and/or mast cells in corneal cytology. Each
      animal was treated with two applications of 2 * 106 million of fAd-MSCs 2 months
      apart. Ocular surface integrity was assessed before treatment and at 1, 3, 6 and
      11 months after treatment. Clinical signs showed a significant change during the
      follow-up with resolution of the corneal and conjunctiva lesions and there were
      no signs of regression or worsening. CONCLUSIONS: Implanted cells were well
      tolerated and effective reducing clinical signs of FEK with a sustained effect
      during the study period. None of the animals showed systemic or local
      complications during the study. To our knowledge, this is the first time in
      literature that local implantation of allogeneic fAd-MSCs has been found as an
      effective therapeutic alternative to treat cats with FEK.

PMID- 29587745
TI  - High antiretroviral therapy service delivery satisfaction and its' associated
      factors at Midre-genet hospital; Northwest Tigray, Ethiopia.
AB  - BACKGROUND: Patient's satisfaction occurs when patients feel their needs and
      expectations are being meet by the service delivery they receive in health
      institutions. The Objective of this research was to assess HIV/AIDS patients'
      satisfaction with antiretroviral therapy service delivery and its associated
      factors at Midre - Genet hospital, Northwest Tigray, Ethiopia. METHODS:
      Institutional based cross-sectional study was conducted. Four hundred twenty
      study respondents were selected using systematic random sampling technique. Data
      was collected using pretested, structured interview questionnaire. Bivariate
      analysis was conducted to identify potential significantly associated variables
      and transferred to multivariate logistic regression analysis. P value < 0.05 is
      used to demarcate significantly associated variables. RESULT: The overall
      HIV/AIDS patients'satisfaction on antiretroviral therapy service delivery at
      Midre-Genet referral hospital was 75.2%. Multivariate analysis revealed age,
      marital status, occupation, income, information provision and guidance, privacy,
      access of toilets and interpersonal communication as significantly associated
      factors with patient's satisfaction on ART service delivery. CONCLUSION: The
      overall HIV/AIDS patients' satisfaction at Midre-Genet referral hospital was
      high. Age, marital status, occupation and, income was associated factors.
      Moreover, lack of functional CD4 machine, inaccessibility of toilets and water,
      waiting time, inadequate counseling services and lack of qualified health worker
      (Doctor) in the ART clinic were also challenges for ART patients in the hospital.

PMID- 29587746
TI  - Do students from public schools fare better in medical school than their
      colleagues from private schools? If so, what can we learn from this?
AB  - BACKGROUND: Internal grade inflation is a documented practice in secondary
      schools (mostly in private schools) that jeopardises fairness with regard to
      access to medical school. However, it is frequently assumed that the higher
      internal grades are in fact justifiable, as they correspond to better preparation
      of students in private schools in areas that national exams do not cover but
      nevertheless are important. Consequently, it is expected that students from
      private schools will succeed better in medical school than their colleagues, or
      at least not perform worse. We aimed to study whether students from private
      schools do fare better in medical school than their colleagues from public
      schools, even after adjusting for internal grade inflation. METHODS: We analysed
      all students that entered into a medical course from 2007 to 2014. A linear
      regression was performed using mean grades for the 1st-year curse units (CU) of
      the medical school curriculum as a dependent variable and student gender, the
      nature of students' secondary school (public/private), and whether their
      secondary school highly inflated grades as independent variables. A logistic
      regression was also performed, modelling whether or not students failed at least
      one CU exam during the 1st year of medical school as a function of the
      aforementioned independent variables. RESULTS: Of the 1709 students analysed, 55%
      came from public secondary schools. Private (vs. public) secondary school (beta =
      - 0.459, p < 0.001) and whether secondary schools highly inflated grades (beta = 
      0.246, p = 0.003) were independent factors that significantly influenced grades
      during the first year of medical school. Having attended a private secondary
      school also significantly increased the odds of a student having failed at least
      one CU exam during the 1st year of medical school (OR = 1.33), even after
      adjusting for whether or not the secondary school used highly inflated grades.
      CONCLUSIONS: It is important to further discuss what we can learn from the fact
      that students from public secondary schools seem to be better prepared for
      medical school teaching methodologies than their colleagues from private ones and
      the implications for the selection process.

PMID- 29587747
TI  - Memantine loaded PLGA PEGylated nanoparticles for Alzheimer's disease: in vitro
      and in vivo characterization.
AB  - BACKGROUND: Memantine, drug approved for moderate to severe Alzheimer's disease,
      has not shown to be fully effective. In order to solve this issue, polylactic-co
      glycolic (PLGA) nanoparticles could be a suitable solution to increase drug's
      action on the target site as well as decrease adverse effects. For these reason,
      Memantine was loaded in biodegradable PLGA nanoparticles, produced by double
      emulsion method and surface-coated with polyethylene glycol. MEM-PEG-PLGA
      nanoparticles (NPs) were aimed to target the blood-brain barrier (BBB) upon oral
      administration for the treatment of Alzheimer's disease. RESULTS: The production
      parameters were optimized by design of experiments. MEM-PEG-PLGA NPs showed a
      mean particle size below 200 nm (152.6 +/- 0.5 nm), monomodal size distribution
      (polydispersity index, PI < 0.1) and negative surface charge (- 22.4 mV).
      Physicochemical characterization of NPs confirmed that the crystalline drug was
      dispersed inside the PLGA matrix. MEM-PEG-PLGA NPs were found to be non-cytotoxic
      on brain cell lines (bEnd.3 and astrocytes). Memantine followed a slower release
      profile from the NPs against the free drug solution, allowing to reduce drug
      administration frequency in vivo. Nanoparticles were able to cross BBB both in
      vitro and in vivo. Behavioral tests carried out on transgenic APPswe/PS1dE9 mice
      demonstrated to enhance the benefit of decreasing memory impairment when using
      MEM-PEG-PLGA NPs in comparison to the free drug solution. Histological studies
      confirmed that MEM-PEG-PLGA NPs reduced beta-amyloid plaques and the associated
      inflammation characteristic of Alzheimer's disease. CONCLUSIONS: Memantine NPs
      were suitable for Alzheimer's disease and more effective than the free drug.

PMID- 29587749
TI  - FOLFIRI plus panitumumab in the treatment of wild-type KRAS and wild-type NRAS
      metastatic colorectal cancer.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy and safety of
      first-line panitumumab plus folinic acid, 5-fluorouracil and irinotecan (FOLFIRI)
      in patients with wild-type KRAS and wild-type NRAS metastatic colorectal cancer
      (mCRC). METHODS: Patients with wild-type KRAS and wild-type NRAS mCRC presenting
      to the medical oncology department of the Okmeydani Training and Research
      Hospital in Istanbul, Turkey, between April 2014 and January 2018 were enrolled
      in this study. RESULTS: A total of 64 patients (35 males and 29 females) with a
      median age of 59 (35-81) years old were enrolled. The median follow-up was 18.9
      months, and the median progression-free survival was 13 months. The median
      overall survival (OS) was 26 months in the patients with wild-type KRAS and wild
      type NRAS mCRC. It was 90.4% for the 6-month OS, 79.5% for the 1-year OS, 53.7%
      for the 2-year OS and 31.1% for the 3-year OS. The median OS of the patients who
      underwent metastasectomies was 40 [95% confidence interval (CI) = 19.9-60.1]
      months, and the median OS of the patients without metastasectomies was 22 (95% CI
      = 17.7-26.4) months. There was a statistically significant difference between
      these (P = 0.007). CONCLUSION: The first-line FOLFIRI plus panitumumab was
      associated with favourable efficacy in the patients with wild-type KRAS and wild
      type NRAS mCRC, and it was well tolerated. The removal of the metastases that
      became resectable after chemotherapy further prolonged the patients' survival.
      TRIAL REGISTRATION: Retrospectively registered: 33886.

PMID- 29587748
TI  - Regulation of alveolar macrophage death in acute lung inflammation.
AB  - Acute lung injury (ALI) and its severe form, known as acute respiratory distress
      syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic
      inflammatory responses that result from conditions such as sepsis, trauma, and
      major surgery. The reciprocal influences between pulmonary and systemic
      inflammation augments the inflammatory process in the lung and promotes the
      development of ALI. Emerging evidence has revealed that alveolar macrophage (AM)
      death plays important roles in the progression of lung inflammation through its
      influence on other immune cell populations in the lung. Cell death and tissue
      inflammation form a positive feedback cycle, ultimately leading to exaggerated
      inflammation and development of disease. Pharmacological manipulation of AM death
      signals may serve as a logical therapeutic strategy for ALI/ARDS. This review
      will focus on recent advances in the regulation and underlying mechanisms of AM
      death as well as the influence of AM death on the development of ALI.

PMID- 29587750
TI  - Three-dimensional experiments and individual based simulations show that cell
      proliferation drives melanoma nest formation in human skin tissue.
AB  - BACKGROUND: Melanoma can be diagnosed by identifying nests of cells on the skin
      surface. Understanding the processes that drive nest formation is important as
      these processes could be potential targets for new cancer drugs. Cell
      proliferation and cell migration are two potential mechanisms that could
      conceivably drive melanoma nest formation. However, it is unclear which one of
      these two putative mechanisms plays a dominant role in driving nest formation.
      RESULTS: We use a suite of three-dimensional (3D) experiments in human skin
      tissue and a parallel series of 3D individual-based simulations to explore
      whether cell migration or cell proliferation plays a dominant role in nest
      formation. In the experiments we measure nest formation in populations of
      irradiated (non-proliferative) and non-irradiated (proliferative) melanoma cells,
      cultured together with primary keratinocyte and fibroblast cells on a 3D
      experimental human skin model. Results show that nest size depends on initial
      cell number and is driven primarily by cell proliferation rather than cell
      migration. CONCLUSIONS: Nest size depends on cell number, and is driven primarily
      by cell proliferation rather than cell migration. All experimental results are
      consistent with simulation data from a 3D individual based model (IBM) of cell
      migration and cell proliferation.

PMID- 29587751
TI  - Plasma angiopoietin-like 4 is related to phospholipid transfer protein activity
      in diabetic and non-diabetic subjects: role of enhanced low grade inflammation.
AB  - BACKGROUND: Angiopoietin-like 4 (ANGPTL4) inhibits lipoprotein lipase, whereas
      phospholipid transfer protein (PLTP) enhances hepatic triglyceride secretion.
      Both factors may be upregulated by inflammatory pathways. Since the extent to
      which these circulating factors are interrelated is unknown, we determined the
      relationship between plasma ANGPTL4 and PLTP activity, and assessed whether such
      a relationship could be explained by high sensitivity C-reactive protein (hsCRP)
      levels as a marker of low-grade chronic inflammation. METHODS: Fasting plasma
      ANGPTL4, PLTP activity (liposome-vesicle high density lipoprotein system) and
      hsCRP were measured in 41 type 2 diabetic (T2DM) subjects and 36 non-diabetic
      subjects. RESULTS: Plasma ANGPTL4 and PLTP activity were increased in T2DM (p <
      0.001 for each), coinciding with elevated hsCRP, triglycerides and non-esterified
      fatty acids (NEFA) (p = 0.031 to 0.001). In univariate analysis, ANGTLP4 was
      correlated with PLTP activity (Rs = 0.309, p = 0.006), whereas both factors were
      related to hsCRP and NEFA levels (Rs = 0.304 to 0.411, p < 0.01 to < 0.001). In
      multivariable linear regression analysis adjusting for age, sex, glucose, total
      cholesterol, triglycerides and NEFA, ANGPTL4 and PLTP activity each remained
      positively associated with hsCRP (beta = 0.315, p = 0.003 and beta = 0.299, p =
      0.034, respectively). Plasma ANGPTL4 remained positively associated with PLTP
      activity when taking account of age, sex, glucose, total cholesterol,
      triglycerides and NEFA (beta = 0.315, p = 0.003). Notably, this association
      disappeared after further adjustment for hsCRP (beta = 0.131, p = 0.25).
      CONCLUSIONS: In conclusion, plasma ANGPTL4 and PLTP activity are interrelated,
      which may at least in part be explained by low-grade chronic inflammation. A pro
      inflammatory state could affect triglyceride metabolism via concerted effects on
      ANGPTL4 and PLTP.

PMID- 29587752
TI  - Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit
      detected by magnetic resonance imaging.
AB  - BACKGROUND: Hypercholesterolemia is known to increase the risk of AD in later
      life, the purpose of this study is to illustrate brain metabolic and structural
      changes in a cholesterol-fed rabbit model of Alzheimer's Disease (AD) by using
      clinical 3 T Magnetic Resonance Imaging (MRI). METHODS: The Institutional Animal
      Care and Use Committee of Zhejiang Chinese Medical University approved the study.
      Totally 16 Japanese White Rabbits (JWR) were randomly divided into 2 groups
      including normal control group fed with routine diet (group NC) and high
      cholesterol diet group (group CD) fed a 2% cholesterol diet with 0.24 ppm copper
      in the drinking water for 12 weeks. Magnetic resonance spectroscopy (MRS) and
      structural image of rabbit brain were performed by using a 3 Tesla (T) MRI
      scanner with an 8 channel Rabbit coil. The chemical metabolites were identified
      by LC Model including N-acetylaspartate (NAA), creatine (Cr), glutamate (Glu),
      glutamine (Gln), Glycerophosphatidylcholine (GPC), phosphorylcholine (PCH), and
      myoinositol (MI). The relative concentrations (/Cr) were analyzed. Additionally,
      Amyloid-beta (Abeta) accumulation in the brain was measured postmortem. For
      comparisons of MR and Abeta data between groups, two-tailed t-tests were
      performed. RESULTS: The ratio of NAA/Cr (0.76 +/- 0.10) and Glu/Cr (0.90 +/-
      0.14) in group CD were lower than those in the group NC (0.87 +/- 0.06, 1.13 +/-
      0.22, respectively, P <  0.05). Compared to the group NC (2.88 +/- 0.09 cm3, 0.63
      +/- 0.08 cm3, respectively), the cortical and hippocampal volumes (2.60 +/- 0.14
      cm3 and 0.47 +/- 0.07 cm3, respectively) of rabbits brain decreased in the group
      CD while the third and lateral ventricular volumes enlarged (44.56 +/- 6.01 mm3
      vs 31.40 +/- 6.14 mm3, 261.40 +/- 30.98 mm3 vs 153.81 +/- 30.08 mm3, P <  0.05).
      These metabolic and structural changes were additionally accompanied by the
      significant increase of Abeta1-42 in the cortex and hippocampus (163.60 +/- 16.26
      pg/mg and 215.20 +/- 69.86 pg/mg, respectively, P <  0.05). CONCLUSION: High
      cholesterol diet can induce the brain metabolic and structural changes of the
      rabbit including lowered level of NAA and Glu and the atrophy of the brain which
      were similar to those of human AD.

PMID- 29587753
TI  - Exposure to hazardous air pollutants and risk of incident breast cancer in the
      nurses' health study II.
AB  - BACKGROUND: Findings from a recent prospective cohort study in California
      suggested increased risk of breast cancer associated with higher exposure to
      certain carcinogenic and estrogen-disrupting hazardous air pollutants (HAPs).
      However, to date, no nationwide studies have evaluated these possible
      associations. Our objective was to examine the impacts of mammary carcinogen and
      estrogen disrupting HAPs on risk of invasive breast cancer in a nationwide
      cohort. METHODS: We assigned HAPs from the US Environmental Protection Agency's
      2002 National Air Toxics Assessment to 109,239 members of the nationwide,
      prospective Nurses' Health Study II (NHSII). Risk of overall invasive, estrogen
      receptor (ER)-positive (ER+), and ER-negative (ER-) breast cancer with increasing
      quartiles of exposure were assessed in time-varying multivariable proportional
      hazards models, adjusted for traditional breast cancer risk factors. RESULTS: A
      total of 3321 invasive cases occurred (2160 ER+, 558 ER-) during follow-up 1989
      2011. Overall, there was no consistent pattern of elevated risk of the HAPs with
      risk of breast cancer. Suggestive elevations were only seen with increasing 1,2
      dibromo-3-chloropropane exposures (multivariable adjusted HR of overall breast
      cancer = 1.12, 95% CI: 0.98-1.29; ER+ breast cancer HR = 1.09; 95% CI: 0.92,
      1.30; ER- breast cancer HR = 1.14; 95% CI: 0.81, 1.61; each in the top exposure
      quartile compared to the lowest). CONCLUSIONS: Exposures to HAPs during adulthood
      were not consistently associated with an increased risk of overall or estrogen
      receptor subtypes of invasive breast cancer in this nationwide cohort of women.

PMID- 29587754
TI  - Retrograde intubation in a dog with severe temporomandibular joint ankylosis:
      case report.
AB  - BACKGROUND: Orotracheal intubation in dogs is a common and easily-performed
      procedure that provides a patent airway during anaesthesia. In dogs with
      temporomandibular joint ankylosis or pseudo-ankylosis, airway management can be a
      challenging procedure since these dogs have a limited ability to open their
      mouth. Methods to provide safe, uneventful intubation in such patients may
      include minimally invasive techniques such as retrograde intubation using a guide
      wire and fibre-optic-aided laryngoscopy. CASE PRESENTATION: We report a case of a
      16-month-old, intact female Bull Terrier weighing 17 kg, admitted to the hospital
      for surgical treatment of bilateral ankylosis of the temporomandibular joint.
      Intubation was achieved, without direct observation of the larynx, by retrograde
      intubation using a vascular access catheter and a vascular wire guide through
      cricothyroid membrane. Bilateral condylectomy was performed and the dog recovered
      uneventfully. CONCLUSIONS: In conclusion, retrograde intubation was relatively
      simple to perform with the guide wire technique and no specific training or
      equipment were necessary.

PMID- 29587755
TI  - Torulene and torularhodin: "new" fungal carotenoids for industry?
AB  - Torulene and torularhodin represent the group of carotenoids and are synthesized
      by yeasts and fungi. The most important producers of these two compounds include
      yeasts of Rhodotorula and Sporobolomyces genera. The first reports confirming the
      presence of torulene and torularhodin in the cells of microorganisms date to the
      1930s and 1940s; however, only in the past few years, the number of works
      describing the properties of these compounds increased. These compounds have
      strong anti-oxidative and anti-microbial properties, and thus may be successfully
      used as food, feedstock, and cosmetics additives. In addition, tests performed on
      rats and mice showed that both torulene and torularhodin have anti-cancerous
      properties. In order to commercialize the production of these two carotenoids, it
      is necessary to obtain highly efficient yeast strains, for example, via
      mutagenization and optimization of cultivation conditions. Further studies on the
      activity of torulene and torularhodin on the human body are also needed.

PMID- 29587756
TI  - The effect of industry-related air pollution on lung function and respiratory
      symptoms in school children.
AB  - BACKGROUND: Heavy industry emits many potentially hazardous pollutants into the
      air which can affect health. However, the effects of air pollution from heavy
      industry on lung function and respiratory symptoms have been investigated
      scarcely. Our aim was to investigate the associations of long-term air pollution
      from heavy industry with lung function and respiratory symptoms in school
      children. METHODS: A cross-sectional lung function study was conducted among
      school children (7-13 years) in the vicinity of an area with heavy industry. Lung
      function measurements were conducted during school hours. Parents of the children
      were asked to complete a questionnaire about the health of their children. A
      dispersion model was used to characterize the additional individual-level
      exposures to air pollutants from the industry in the area. Associations between
      PM2.5 and NOX exposure with lung function and presence of respiratory symptoms
      were investigated by linear and/or logistic regression analysis. RESULTS:
      Participation in the lung function measurements and questionnaires was 84%
      (665/787) and 77% (603/787), respectively. The range of the elevated PM2.5 and
      NOX five years average concentrations (2008-2012) due to heavy industry were 0.04
      1.59 MUg/m3 and 0.74-11.33 MUg/m3 respectively. After adjustment for confounders
      higher exposure to PM2.5 and NOX (per interquartile range of 0.56 and 7.43 MUg/m3
      respectively) was associated with lower percent predicted peak expiratory flow
      (PEF) (B -2.80%, 95%CI -5.05% to - 0.55% and B -3.67%, 95%CI -6.93% to - 0.42%
      respectively). Higher exposure to NOX (per interquartile range of 7.43 MUg/m3)
      was also associated with lower percent forced vital capacity (FVC) and percent
      predicted forced expiration volume in 1 s (FEV1) (B -2.30, 95% CI -4.55 to - 0.05
      and B -2.73, 95%CI -5.21 to - 0.25 respectively). No significant associations
      were found between the additional exposure to PM2.5 or NOX and respiratory
      symptoms except for PM2.5 and dry cough (OR 1.40, 95%CI 1.00 to 1.94).
      CONCLUSION: Exposure to PM2.5 and NOX from industry was associated with decreased
      lung function. Exposure to PM2.5 was also associated with parents' reports of dry
      cough among their children.

PMID- 29587757
TI  - Single metastasis of myxoid liposarcoma from the thigh to thyroid gland: a case
      report.
AB  - BACKGROUND: Thyroid metastasis of soft tissue sarcoma is very rare, and the
      diagnosis is especially difficult when only a single lesion is present. CASE
      PRESENTATION: A 50-year-old man was diagnosed with myxoid liposarcoma of the
      right thigh and treated with wide resection. Two and a half years after the
      surgery, a growing low-density area was incidentally observed in the right lobe
      of his thyroid gland on follow-up chest computed tomography. Fine needle
      aspiration biopsy was performed twice, and the thyroid mass was suspected of
      being a sarcoma metastasis. He was treated by hemithyroidectomy, and the lesion
      was pathologically confirmed as a metastasis of myxoid liposarcoma. CONCLUSION:
      We experienced single thyroid gland metastasis in patients with myxoid
      liposarcoma in whom a growing mass is observed in the thyroid gland after radical
      surgery of the primary site.

PMID- 29587758
TI  - Prediction equations of forced oscillation technique: the insidious role of
      collinearity.
AB  - Many studies have reported reference data for forced oscillation technique (FOT)
      in healthy children. The prediction equation of FOT parameters were derived from
      a multivariable regression model examining the effect of age, gender, weight and
      height on each parameter. As many of these variables are likely to be correlated,
      collinearity might have affected the accuracy of the model, potentially resulting
      in misleading, erroneous or difficult to interpret conclusions.The aim of this
      work was: To review all FOT publications in children since 2005 to analyze
      whether collinearity was considered in the construction of the published
      prediction equations. Then to compare these prediction equations with our own
      study. And to analyse, in our study, how collinearity between the explanatory
      variables might affect the predicted equations if it was not considered in the
      model. The results showed that none of the ten reviewed studies had stated
      whether collinearity was checked for. Half of the reports had also included in
      their equations variables which are physiologically correlated, such as age,
      weight and height. The predicted resistance varied by up to 28% amongst these
      studies. And in our study, multicollinearity was identified between the
      explanatory variables initially considered for the regression model (age, weight
      and height). Ignoring it would have resulted in inaccuracies in the coefficients
      of the equation, their signs (positive or negative), their 95% confidence
      intervals, their significance level and the model goodness of fit. In Conclusion
      with inaccurately constructed and improperly reported models, understanding the
      results and reproducing the models for future research might be compromised.

PMID- 29587759
TI  - Anxiety and its predictive value for pain and regular analgesic intake after
      lumbar disc surgery - a prospective observational longitudinal study.
AB  - BACKGROUND: Ongoing pain after surgery is a major problem and influences recovery
      and the quality of life of the patient. Associations between anxiety and their
      impact on postoperative pain after herniated disc surgery have been reported, but
      the results are inconsistent. The aim of the present longitudinal study was to
      evaluate the predictive value of preoperative anxiety for postoperative ongoing
      pain and prolonged analgesic intake after herniated disc surgery. METHODS: 106
      patients with lumbar disc herniation were evaluated in the study. Anxiety was
      measured with the Generalized Anxiety Disorder 7-Item Scale (GAD-7) before
      surgery. Pain intensity was assessed on a numeric rating scale (NRS) at baseline,
      6-weeks and 6-months after surgery. Regression analysis was performed to identify
      independent predictors of pain and regular utilization of analgesics up to 6
      months after surgery while controlling for confounding variables. RESULTS: 42.5%
      of the patients were rated as anxiety cases (sum scores GAD-7 > 5), mean scores
      of anxiety showed mild to moderate symptom severity, and 43% suffered from
      chronic pain before surgery. Six months after surgery, 55.6% of the patients
      indicated pain levels of 4/10 (NRS) or higher and about 40% still took pain
      medication on a regular basis, regardless of their preoperative classification as
      anxiety-case (37.7% and 41.5%). The preoperative pain level was statistically
      significant for ongoing postsurgical pain in all four analyses (p < 0.001). With
      binary logistic regression analyses, preoperative pain intensity, but neither
      demographic factors nor preoperative anxiety, was identified as predictor for
      postoperative pain and need for analgesic medication up to 6 months after lumbar
      disc surgery. CONCLUSION: We found no evidence for the presence of anxiety before
      disc surgery being a prognostic factor for ongoing pain and regular postoperative
      intake of analgesics. Only preoperative pain intensity was predictive for
      increased pain and continued need for analgesic medication up to 6 months after
      lumbar disc surgery. TRIAL REGISTRATION: Clinicaltrials.gov NCT01488617 .
      Registered 6 December 2011.

PMID- 29587760
TI  - The prognostic significance of topoisomerase II alpha protein in early stage
      luminal breast cancer.
AB  - BACKGROUND: Topoisomerase II alpha (TOP2A) protein has been shown to be a
      proliferation marker associated with tumor grade and Ki67 index. The prognostic
      effect of TOP2A seems different among different subtypes of breast cancer. The
      current study evaluated the prognostic impact of TOP2A protein on luminal breast
      cancer. METHOD: Altogether 434 stage I-II luminal breast cancer patients who
      underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007
      and 2009 were enrolled. TOP2A protein expression was assessed by
      immunohistochemistry. Clinical and pathological data were retrospectively
      collected. RESULT: With a cut-off value of 30%, 127 (29.3%) patients were
      classified as TOP2A overexpression. TOP2A overexpression was associated with a
      higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a
      significantly higher rate of distant metastasis and shorter distant metastasis
      free survival (DMFS) compared with patients with low TOP2A expression. The
      prognostic influence of TOP2A expression was more significant in years 5-8 after
      diagnosis, and more pronounced in stage II patients, luminal B disease, and
      patients treated with adjuvant endocrine therapy alone. Multivariate survival
      analysis revealed TOP2A overexpression was an independent fact for worse DMFS.
      CONCLUSION: TOP2A protein showed a time dependent influence on prognosis in stage
      I-II luminal breast cancer, suggesting it might be a potential predictor of late
      recurrence for this group of patients.

PMID- 29587762
TI  - Analysis of medication consultation networks and reporting medication errors: a
      mixed methods study.
AB  - BACKGROUND: To examine characteristics of verbal consultation about medication
      within social networks of hospital inpatient medication system, and their
      associations with medication error reporting. METHOD: The setting was a 90-bed
      provincial district hospital with 4 wards, 7 physicians, 5 pharmacists, 44
      nurses, 5 pharmacist assistants, and 4 unskilled ancillary workers. A mixed
      method comprising (i) a prospective observational study for investigating
      incidences and the nature of reporting medication errors, and (ii) a social
      network analysis for patterns of interaction. RESULTS: Out of 5296 prescriptions,
      132 medication errors were reported during the one month study period: an
      incidence rate of 2.5%. Every incident of medication errors was formally
      documented through pharmacists. The most frequent medication errors were in pre
      transcribing (n = 54; 40.9%). The pharmacists were central in the whole network
      of consultation on medication with the mean in-degree centrality of 35 (SD 14.9)
      and mean out-degree centrality of 15.4 (SD 11.1). Two bridging participants were
      identified who were influential communicators connecting the network (betweenness
      centrality). Medication error reporting were influenced by (i) participants whose
      advice is sought and viewed as trustworthy (in-degree centrality; p < 0.001),
      (ii) sex (p = 0.01), and (iii) level of education (p = 0.04). CONCLUSION: In
      degree centrality was the most important network characteristic. A culture of
      medication safety can be fostered by encouraging consultation about the
      medication of in-patients within the hospital network where reporting of
      medication errors is essential.

PMID- 29587761
TI  - Evaluation of oxidative stress biomarkers in idiopathic pulmonary fibrosis and
      therapeutic applications: a systematic review.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF), a fatal lung disease of
      unknown origin, is characterized by chronic and progressive fibrosing
      interstitial pneumonia which progressively impairs lung function. Oxidative
      stress is one of the main pathogenic pathways in IPF. The aim of this systematic
      review was to describe the type of markers of oxidative stress identified in
      different biological specimens and the effects of antioxidant therapies in
      patients with IPF. METHODS: We conducted a systematic search of publications
      listed in electronic databases (Pubmed, Web of Science, Scopus and Google
      Scholar) from inception to October 2017. Two investigators independently reviewed
      all identified articles to determine eligibility. RESULTS: After a substantial
      proportion of the initially identified articles (n = 554) was excluded because
      they were duplicates, abstracts, irrelevant, or did not meet the selection
      criteria, we identified 30 studies. In each study, we critically appraised the
      type, site (systemic vs. local, e.g. breath, sputum, expired breath condensate,
      epithelial lining fluid, bronchoalveolar lavage, and lung tissue specimens), and
      method used for measuring the identified oxidative stress biomarkers.
      Furthermore, the current knowledge on antioxidant therapies in IPF was
      summarized. CONCLUSIONS: A number of markers of oxidative stress, with individual
      advantages and limitations, have been described in patients with IPF.
      Nevertheless, trials of antioxidant treatments have been unable to demonstrate
      consistent benefits, barring recent pharmacogenomics data suggesting different
      results in specific genotype subgroups of patients with IPF.

PMID- 29587763
TI  - On designing of a low leakage patient-centric provider network.
AB  - BACKGROUND: When a patient in a provider network seeks services outside of their
      community, the community experiences a leakage. Leakage is undesirable as it
      typically leads to higher out-of-network cost for patient and increases barrier
      for care coordination, which is particularly problematic for Accountable Care
      Organization (ACO) as the in-network providers are financially responsible for
      quality of care and outcome. We aim to design a data-driven method to identify
      naturally occurring provider networks driven by diabetic patient choices, and
      understand the relationship among provider composition, patient composition, and
      service leakage pattern. By doing so, we learn the features of low service
      leakage provider networks that can be generalized to different patient
      population. METHODS: Data used for this study include de-identified healthcare
      insurance administrative data acquired from Capital District Physicians' Health
      Plan (CDPHP) for diabetic patients who resided in four New York state counties
      (Albany, Rensselaer, Saratoga, and Schenectady) in 2014. We construct a
      healthcare provider network based on patients' historical medical insurance
      claims. A community detection algorithm is used to identify naturally occurring
      communities of collaborating providers. For each detected community, a profile is
      built using several new key measures to elucidate stakeholders of our findings.
      Finally, import-export analysis is conducted to benchmark their leakage pattern
      and identify further leakage reduction opportunity. RESULTS: The design yields
      six major provider communities with diverse profiles. Some communities are
      geographically concentrated, while others tend to draw patients with certain
      diabetic co-morbidities. Providers from the same healthcare institution are
      likely to be assigned to the same community. While most communities have high
      within-community utilization and spending, at 85% and 86% respectively, leakage
      still persists. Hence, we utilize a metric from import-export analysis to detect
      leakage, gaining insight on how to minimize leakage. CONCLUSIONS: We identify
      patient-driven provider organization by surfacing providers who share a large
      number of patients. By analyzing the import-export behavior of each identified
      community using a novel approach and profiling community patient and provider
      composition we understand the key features of having a balanced number of PCP and
      specialists and provider heterogeneity.

PMID- 29587764
TI  - pH-responsive theranostic nanocomposites as synergistically enhancing positive
      and negative magnetic resonance imaging contrast agents.
AB  - BACKGROUND: The rational design of theranostic nanoprobe to present responsive
      effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu
      plays a vital role for efficient personalized cancer therapy and other biomedical
      applications. We aimed to afford a potential strategy to pose both T1- and T2
      weighted MRI functions, and thereby realizing imaging guided drug delivery and
      targeted therapy. RESULTS: Theranostic nanocomposites Mn-porphyrin&Fe3O4@SiO2@PAA
      cRGD were fabricated and characterized, and the nanocomposites were effectively
      used in T1- and T2-weighted MRI and pH-responsive drug release. Fluorescent
      imaging also showed that the nanocomposites specifically accumulated in lung
      cancer cells by a receptor-mediated process, and were nontoxic to normal cells.
      The r2/r1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH
      5.0, suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agent at
      acidic environments of tumor. For in vivo MRI, T1 and T2 relaxation was
      significantly accelerated to 55 and 37%, respectively, in the tumor after i.v.
      injection of nanocomposites. CONCLUSION: The synthesized nanocomposites exhibited
      highly sensitive MRI contrast function no matter in solution, cells or in vivo by
      synergistically enhancing positive and negative magnetic resonance imaging
      signals. The nanocomposites showed great potential for integrating imaging
      diagnosis and drug controlled release into one composition and providing real
      time imaging with greatly enhanced diagnostic accuracy during targeted therapy.

PMID- 29587765
TI  - Occupational exposure to asphalt mixture during road paving is related to
      increased mitochondria DNA copy number: a cross-sectional study.
AB  - BACKGROUND: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from
      hot mix asphalt via both inhalation and dermal absorption. The use of crumb
      rubber modified (CRM) asphalt may result in higher exposure to PAHs and more
      adverse effects. Our aim is to assess occupational exposure to PAHs from
      conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to
      investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere
      length. METHODS: We recruited 116 workers paving conventional asphalt, 51 workers
      paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures
      analysis included 31 workers paving both types of asphalt. Urine and blood
      samples were collected pre-working on Monday morning and post-working on Thursday
      afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2
      hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative
      mtDNAcn and telomere length were measured by quantitative PCR. RESULTS:
      Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than
      controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher
      in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt
      workers compared to controls. Relative telomere length did not differ across
      occupational groups, but it was positively associated with increment of 2-OH-PH
      (beta = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis
      showed no difference in either increment of 1-OH-PYP, or changes in effect
      biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM
      asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt.
      CONCLUSIONS: Road asphalt paving in open areas resulted in PAHs exposure, as
      shown by elevation of PAH metabolites in urine. Asphalt workers may experience
      oxidative stress, evidenced by alternation in mtDNAcn; however the effects could
      not be fully explained by exposure to PAHs from the asphalt mixture.

PMID- 29587766
TI  - ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight
      elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism
      in ARDB1.
AB  - BACKGROUND: In some populations, obesity and body weight related disorders show a
      correlation with polymorphisms in three subtypes of beta-adrenoceptor (beta1,
      beta2, and beta3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism
      of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi
      population to determine association, if any, of these polymorphisms with obesity
      and related disorders. METHODS: We studied 329 non-related adults (33.1% men and
      66.9% women), aged 18-36 years. Anthropometric measurements were recorded, and
      Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin,
      lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3
      polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA
      sequencing. The subjects were divided into three groups according to BMI: normal
      weight (BMI < 25 kg/m2), overweight (BMI >=25.1-29.9 kg/m2) subjects, and obese
      (>=30 kg/m2). RESULTS: In the age-matched groups of the normal weight, overweight
      and obese male and female subjects, all anthropometric parameters were found to
      be significantly higher, and in the obese group, all biochemical parameters were
      significantly elevated compared to the normal weight controls. The allelic
      frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the
      frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and
      obese subjects, compared with the normal weight subjects. In addition, subjects
      carrying Arg64 allele regardless of their BMI had a greater waist and hip
      circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin,
      and glucose level compared to those with the wild-type Trp allele. CONCLUSION:
      The results of this study have shown a significant association between the
      Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity
      in Saudi populations. It also has an influence on the levels of lipid, insulin,
      leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated
      with overweight, obesity or dyslipidaemias in Saudis.

PMID- 29587768
TI  - Antibiotic resistance pattern and virulence genes content in avian pathogenic
      Escherichia coli (APEC) from broiler chickens in Chitwan, Nepal.
AB  - BACKGROUND: Avian pathogenic Escherichia coli (APEC) are causative agent of
      extraintestinal infections, collectively known as colibacillosis, which results
      significant losses in poultry industries. The extraintestinal survival of E. coli
      is facilitated by numerous virulence factors which are coded by virulence genes.
      This study was conducted to find out the pattern of antibiotic resistance and
      virulence genes content in the APEC strains isolated from broiler chickens at
      National Avian Disease Investigation Laboratory and Veterinary Teaching Hospital,
      Rampur, Chitwan, Nepal. RESULTS: A total of 50 E. coli strains were isolated from
      50 colibacillosis suspected broiler chickens. Out of 50 isolates of E. coli, 47
      (94%) showed resistant to three or more antimicrobials. The highest levels (22%)
      of multidrug-resistant E. coli were observed for five different types of
      antimicrobials. Antibiogram profiles of 50 E. coli strains showed the maximum
      resistance to ampicillin (98%), followed by co-trimoxazole (90%), and doxycycline
      (62%). The highest intermediate resistance was shown by colistin (50%) and the
      highest sensitivity was against amikacin (84%), followed by nitrofurantoin (55%).
      Based on the genetic criteria, 45 (90%) E. coli isolates were considered as
      pathogenic (APEC) which contained more than five virulence genes. Out of total
      APEC genes detected, we found the combination of iss, iucD, hlyF, ompT, iroN, and
      iutA genes were mostly associated with the APEC and additionally, to some lesser
      extent irp2, papC, Cva/cvi, and tsh genes showed the critical role for virulent
      traits of APEC strains. CONCLUSION: In this study, high prevalent of
      antimicrobial resistant pattern was found with avian pathogenic E. coli strains
      isolated from broiler chickens. To our knowledge, this is the first molecular
      analysis which confirmed the prevalence of APEC strains in poultry sector in
      Nepal. These finding suggest the need of surveillance and intervention system to
      control misuse of antibiotics and APEC outbreak in the poultry farm.

PMID- 29587769
TI  - Circulating osteopontin and its association with liver fat content in non-obese
      women with polycystic ovary syndrome: a case control study.
AB  - BACKGROUND: Osteopontin (OPN) plays an important role in inflammatory processes
      and insulin resistance. Polycystic ovary syndrome (PCOS) is a reproductive
      metabolic disease associated with insulin resistance and metabolic abnormalities,
      including high levels of liver fat content (LFC). The objective of this study was
      to explore whether circulating OPN independently contributes to elevated LFC in
      non-obese PCOS patients. METHODS: This study included 61 non-obese PCOS patients
      and 56 age-matched healthy women from Shanghai, China. After an overnight fast,
      all participants underwent anthropometric measurements, oral glucose tolerance
      tests, lipid profile and sex hormone measurements. Quantitative measurement of
      LFC by ultrasonography was performed. OPN concentrations were measured using
      ELISA. An independent samples t-test and the Mann-Whitney U test were performed
      to compare variables between the two groups; one-way ANOVA and Kruskal-Wallis
      test were performed to compare four subgroups of patients. Correlations were
      determined by Spearman's correlation tests. Stepwise multiple linear regression
      analyses were performed to assess for independent contributors. A receiver
      operating characteristic curve with the maximum Youden index was calculated for
      the optimal cut-off value. RESULTS: In non-obese PCOS women, circulating OPN
      levels were increased in the subgroups with a higher body mass index (BMI) and
      free androgen index (FAI), and the LFC levels were increased in the elevated OPN
      subgroups. Moreover, increased OPN was associated with increased FAI and LFC in
      PCOS women, and the association between OPN and LFC was independent of
      triglyceride, HOMA-IR and FAI after adjusting for PCOS status in all
      participants. OPN combined with FAI and hsCRP may better predict NAFLD than WHR
      in this study cohort. However, there was no significant difference in circulating
      OPN levels between non-obese PCOS and normal control women. CONCLUSIONS:
      Increased OPN levels may be related to FAI and elevated LFC in non-obese women
      with PCOS.

PMID- 29587770
TI  - Powdered black cumin seeds strongly improves serum lipids, atherogenic index of
      plasma and modulates anthropometric features in patients with Hashimoto's
      thyroiditis.
AB  - BACKGROUND: Hashimoto's thyroiditis is associated with serious alterations in
      serum lipids and glucose homeostasis. The aims of the current study were to
      evaluate the effect of powdered Nigella sativa on serum lipids, glucose
      homeostasis and anthropometric variables in patients with Hashimoto's
      thyroiditis. METHODS: Forty patients with Hashimoto's thyroiditis, aged between
      22 and 50 years old, participated in the trial and were randomly allocated into
      two groups of intervention and control receiving powdered Nigella sativa or
      placebo daily for 8 weeks. Serum lipids, glucose homeostasis, and anthropometric
      variables were evaluated at baseline and after intervention. RESULTS: Treatment
      with Nigella sativa significantly reduced body weight and body mass index (BMI).
      Serum concentrations of low density lipoprotein cholesterol (LDL) and
      triglyceride (TG) also decreased in Nigella sativa-treated group after 8 weeks;
      while serum high density lipoprotein cholesterol (HDL) significantly increased
      after treatment with Nigella sativa (P < 0.05). None of these changes had been
      observed in placebo treated group. Serum Nesfatin-1 concentrations was in inverse
      relationship with serum triglyceride (TG) (r = - 0.31, P = 0.04). CONCLUSIONS:
      Giving attention to the potent beneficial effects of powdered black cumin seeds
      in improving serum lipid profile and anthropometric features in patients with
      Hashimoto's thyroiditis, this medicinal plant could be considered as a beneficial
      herbal supplement alongside with the disease- specific medications including
      Levothyroxine in management of Hashimoto's thyroiditis- related metabolic
      abnormalities. TRIAL REGISTRATION: Iranian registry of clinical trials
      (registration number IRCT2014090819082N2 - Registered 2014-09-29).

PMID- 29587767
TI  - Opportunities in posthemorrhagic hydrocephalus research: outcomes of the
      Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop.
AB  - The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on
      July 25 and 26, 2016 at the National Institutes of Health. The workshop brought
      together a diverse group of researchers including pediatric neurosurgeons,
      neurologists, and neuropsychologists with scientists in the fields of brain
      injury and development, cerebrospinal and interstitial fluid dynamics, and the
      blood-brain and blood-CSF barriers. The goals of the workshop were to identify
      areas of opportunity in posthemorrhagic hydrocephalus research and encourage
      scientific collaboration across a diverse set of fields. This report details the
      major themes discussed during the workshop and research opportunities identified
      for posthemorrhagic hydrocephalus. The primary areas include (1) preventing
      intraventricular hemorrhage, (2) stopping primary and secondary brain damage, (3)
      preventing hydrocephalus, (4) repairing brain damage, and (5) improving
      neurodevelopment outcomes in posthemorrhagic hydrocephalus.

PMID- 29587771
TI  - Treatment of intraoperatively detected peritoneal carcinomatosis of colorectal
      origin with cytoreductive surgery and intraperitoneal chemotherapy.
AB  - BACKGROUND: Diagnosis of peritoneal carcinomatosis (PC) may be missed by
      preoperative imaging. We are presenting our experience with incidentally detected
      PC of colorectal origin treated with cytoreductive surgery (CRS) and
      intraperitoneal chemotherapy (IPC) at the same operation. METHODS: Between
      January 2010 and September 2016, 19 patients underwent CRS and IPC due to
      incidentally detected PC of colorectal origin. Data were analyzed from a
      prospectively collected database. RESULTS: The median age was 59 (29-78). In
      three patients, PC was diagnosed during emergency surgery. The primary tumor was
      located in the rectum (three patients; one with recurrent disease), left colon (9
      patients), and right colon (7 patients). All patients underwent CRS and IPC, and
      one patient operated laparoscopically. Median peritoneal cancer index (PCI) was 5
      (range, 3-14), and complete cytoreduction (CC-0) was achieved in 14 patients.
      After CRS, 8 patients received early postoperative intraperitoneal chemotherapy
      (EPIC), 7 patients received hyperthermic intraperitoneal chemotherapy (HIPEC),
      and 4 patients received both HIPEC and EPIC. The median hospital stay was 9 (6
      29) days. Postoperative complications occurred in 6 patients. There was no
      postoperative mortality. Median follow-up was 40.2 (12-94) months. Five-year
      overall survival was 63.2%. Estimated mean survival time is longer in patients
      who underwent complete cytoreduction compared to patients having CC-1 or CC-2
      cytoreduction (87.7 vs. 20.3 months; p < 0.001). CONCLUSION: Cytoreductive
      surgery and IPC can be performed safely in patients with intraoperatively
      detected incidental PC of colorectal origin.

PMID- 29587773
TI  - CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization
      in the treatment of hepatocellular carcinoma: a short-term efficacy and safety
      study.
AB  - BACKGROUND: The present study aimed to evaluate the short-term efficacy and
      safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) with
      CalliSpheres Beads loaded with doxorubicin (DOX) in the treatment of Chinese
      patients with hepatocellular carcinoma (HCC) compared to conventional TACE
      (cTACE). METHODS: A total of 54 patients with HCC treated by TACE from June 2016
      to February 2017 were retrospectively analyzed. These included 24 cases in the
      DEB-TACE group and 30 cases in the cTACE group. The clinical efficacy, tumor
      recurrence rate, and complications were compared between the two groups.
      Furthermore, liver function tests and alpha-feto protein levels were compared
      between the two groups before and at 1 week and 1 month after interventional
      treatment. RESULTS: There were no significant differences in baseline
      characteristics (p > 0.05). Tumor response rates and disease control rates in the
      DEB-TACE group were significantly higher than those in the cTACE group at 3 and 6
      months after treatment (p < 0.05). Recurrence rates at 6 months were
      significantly higher for cTACE compared to DEB-TACE (43.3 vs. 16.7%; p = 0.036).
      At 1 month, the AFP level in the DEB-TACE group was significantly lower than that
      in the cTACE group (p = 0.008). At the end of follow-up, four cases in the DEB
      TACE group and two cases in the cTACE group were treated with salvage surgery
      after downstaging the disease. Liver function of both groups improved at 1 month.
      However, alanine aminotransferase, aspartate aminotransferase, and total
      bilirubin levels in the DEB-TACE group were better than those in the cTACE group
      (p < 0.05). The incidence of DOX-related complications in the DEB-TACE group was
      significantly lower than in the cTACE group (p < 0.05). CONCLUSION: The short
      term efficacy of DEB-TACE is better, and the complication rates are lower
      compared to cTACE in the treatment of Chinese patients with HCC. However, long
      term clinical efficacy and survival benefit should be analyzed in future studies.

PMID- 29587772
TI  - Oxidative stress enhances the expression of IL-33 in human airway epithelial
      cells.
AB  - BACKGROUND: Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family,
      and its possible involvement in the pathophysiology of COPD and viral-induced
      exacerbations has been demonstrated. IL-33 has been shown to be increased in the
      airway epithelial cells from COPD patients, but the regulating mechanism of IL-33
      expression in airway epithelial cells remains largely unknown. In the current
      study, we examined whether oxidative stress, which participates in the
      pathogenesis of COPD, affects the expression of IL-33 in airway epithelial cells
      and also evaluated the effect during viral infection. METHODS: The involvement of
      oxidative stress in the expression of IL-33, and its signal pathway was examined
      after stimulation with hydrogen peroxide (H2O2), with or without stimulation by
      polyinosinic-polycytidylic acid [poly (I:C)], a synthetic analogue of dsRNA that
      mimics viral infection, or rhinovirus infection in NCI-H292 cells and primary
      human bronchial epithelial cells (HBECs). In addition, the effect of antioxidant,
      N-acetylcysteine (NAC) in the expression of IL-33 was compared between HBECs from
      healthy subjects and those from COPD patients. RESULTS: Treatment with H2O2
      significantly potentiated IL-33 expression in NCI-H292 cells, and the
      potentiation was reversed by NAC treatment. Mitogen-activated protein kinase
      (MAPK) inhibitors, but not nuclear factor-kappa B inhibitors, also significantly
      decreased the H2O2-potentiated IL-33 expression. In addition, H2O2 significantly
      potentiated the poly (I:C)- or rhinovirus-stimulated IL-33 expression. In HBECs
      from healthy subjects, H2O2-potentiated IL-33 expression and its reversal by NAC
      was also confirmed. Under the condition without H2O2-stimulation, treatment with
      NAC significantly decreased the expression of IL-33 in HBECs from COPD patients,
      but not in those from healthy subjects. CONCLUSIONS: These results demonstrate
      that oxidative stress involves in the expression of IL-33 in airway epithelial
      cells via MAPK signal pathway and it augments IL-33 expression during viral
      infection. This mechanism may participate in the regulation of IL-33 expression
      in airway epithelial cells in COPD and the viral-induced exacerbations.
      Modulation of this pathway could become a therapeutic target for viral-induced
      exacerbations of COPD.

PMID- 29587774
TI  - Detecting spatio-temporal mortality clusters of European countries by sex and
      age.
AB  - BACKGROUND: Mortality decreased in European Union (EU) countries during the last
      century. Despite these similar trends, there are still considerable differences
      in the levels of mortality between Eastern and Western European countries. Sub
      group analysis of mortality in Europe for different age and sex groups is common,
      however to our knowledge a spatio-temporal methodology as in this study has not
      been applied to detect significant spatial dependence and interaction with time.
      Thus, the objective of this paper is to quantify the dynamics of mortality in
      Europe and detect significant clusters of mortality between European countries,
      applying spatio-temporal methodology. In addition, the joint evolution between
      the mortality of European countries and their neighbours over time was studied.
      METHODS: The spatio-temporal methodology used in this study takes into account
      two factors: time and the geographical location of countries and, consequently,
      the neighbourhood relationships between them. This methodology was applied to 26
      European countries for the period 1990-2012. RESULTS: Principally, for people
      older than 64 years two significant clusters were obtained: one of high mortality
      formed by Eastern European countries and the other of low mortality composed of
      Western countries. In contrast, for ages below or equal to 64 years only the
      significant cluster of high mortality formed by Eastern European countries was
      observed. In addition, the joint evolution between the 26 European countries and
      their neighbours during the period 1990-2012 was confirmed. For this reason, it
      can be said that mortality in EU not only depends on differences in the health
      systems, which are a subject to national discretion, but also on supra-national
      developments. CONCLUSIONS: This paper proposes statistical tools which provide a
      clear framework for the successful implementation of development public policies
      to help the UE meet the challenge of rethinking its social model (Social Security
      and health care) and make it sustainable in the medium term.

PMID- 29587775
TI  - New forms of development: branding innovative ideas and bidding for foreign aid
      in the maternal and child health service in Nepal.
AB  - BACKGROUND: Nepal has been receiving foreign aid since the early 1950s.
      Currently, the country's health care system is heavily dependent on aid, even for
      the provision of basic health services to its people. Globally, the mechanism for
      the dispersal of foreign aid is becoming increasingly complex. Numerous
      stakeholders are involved at various levels: donors, intermediary organisations,
      project-implementing partners and the beneficiaries, engaging not only in Nepal
      but also globally. To illustrate how branding and bidding occurs, and to discuss
      how this process has become increasingly vital in securing foreign aid to run MCH
      activities in Nepal. METHOD: This paper is based on a qualitative study. The data
      collection method includes Key Informant Interviews, the review of relevant
      policy documents and secondary data, and finally field observation visits to four
      maternal and child health (MCH) projects, currently funded by foreign aid.
      Through these methods we planned to gain a comprehensive understanding of the aid
      dispersing mechanism, and the aid-securing strategies, used by organisations
      seeking funds to provide MCH services in Nepal. RESULTS: Study findings suggest
      that foreign aid for the provision of MCH services in Nepal is channeled
      increasingly to its beneficiaries, not through the Government system, but rather
      via various intermediary organisations, employing branding and bidding processes.
      These organisations adapt commercial models, seeking to justify their 'cost
      effectiveness'. They argue that they are 'yielding good value for money', with
      short-term target oriented projects. This ethos is evident throughout the aid
      dispersing chain. Organisations use innovative ideas and intervention packages,
      branded internationally and nationally, and employ the appropriate language of
      commerce in their bid to secure funds. The paper raises an important question as
      to whether the current mechanisms of channeling foreign aid in the MCH sector,
      via intermediary organisations, can actually be cost-effective, given the complex
      bureaucratic processes involved. CONCLUSIONS: The study findings are very
      important, for Nepal's development in particular, and for international
      development in general. The paper concludes by recommending strongly that foreign
      aid should concentrate on supporting and strengthening the national government
      system. Complex bureaucratic process must be minimised and streamlined in order
      to provide quality care to the beneficiaries.

PMID- 29587776
TI  - Improved prediction of gestational hypertension by inclusion of placental growth
      factor and pregnancy associated plasma protein-a in a sample of Ghanaian women.
AB  - BACKGROUND: We assessed whether adding the biomarkers Pregnancy Associated Plasma
      Protein-A (PAPP-A) and Placental Growth Factor (PlGF) to maternal clinical
      characteristics improved the prediction of a previously developed model for
      gestational hypertension in a cohort of Ghanaian pregnant women. METHODS: This
      study was nested in a prospective cohort of 1010 pregnant women attending
      antenatal clinics in two public hospitals in Accra, Ghana. Pregnant women who
      were normotensive, at a gestational age at recruitment of between 8 and 13 weeks
      and provided a blood sample for biomarker analysis were eligible for inclusion.
      From serum, biomarkers PAPP-A and PlGF concentrations were measured by the
      AutoDELFIA immunoassay method and multiple of the median (MoM) values corrected
      for gestational age (PAPP-A and PlGF) and maternal weight (PAPP-A) were
      calculated. To obtain prediction models, these biomarkers were included with
      clinical predictors maternal weight, height, diastolic blood pressure, a previous
      history of gestational hypertension, history of hypertension in parents and
      parity in a logistic regression to obtain prediction models. The Area Under the
      Receiver Operating Characteristic Curve (AUC) was used to assess the predictive
      ability of the models. RESULTS: Three hundred and seventy three women
      participated in this study. The area under the curve (AUC) of the model with only
      maternal clinical characteristics was 0.75 (0.64-0.86) and 0.89(0.73-1.00) for
      multiparous and primigravid women respectively. The AUCs after inclusion of both
      PAPP-A and PlGF were 0.82 (0.74-0.89) and 0.95 (0.87-1.00) for multiparous and
      primigravid women respectively. CONCLUSION: Adding the biomarkers PAPP-A and PlGF
      to maternal characteristics to a prediction model for gestational hypertension in
      a cohort of Ghanaian pregnant women improved predictive ability. Further research
      using larger sample sizes in similar settings to validate these findings is
      recommended.

PMID- 29587777
TI  - An evaluation of South Africa's public-private partnership for the localisation
      of vaccine research, manufacture and distribution.
AB  - BACKGROUND: Public-private partnerships (PPPs), widely used as a means of
      leveraging the skills, expertise and resources of the private sector to mutual
      advantage, were similarly adopted by South Africa to support public sector
      delivery. This study has evaluated one such partnership, namely the Biovac
      Institute, which was established in 2003 to cover vaccine research and
      development, manufacturing, and supply. The initiative was highly unusual given
      that it attempted to combine all three aspects in a single PPP. METHODS: The
      research has followed a concurrent mixed methods approach. In the quantitative
      study, data for prices and product volumes were extracted from secondary data
      sources and used to calculate the economic cost and value-for-money of the PPP.
      Simultaneously, a qualitative study was undertaken in which a number of key
      stakeholders were interviewed using a semi-structured questionnaire on their
      perceptions of the PPP's value. RESULTS: The institute earns a premium on the
      procurement cost of a broad range of vaccines required by the South African
      National Department of Health for its immunisation programme, the net value of
      which was US$85.7 million over the period 2010 to 2014. These funds were used to
      finance the institute's operations, including vaccine research, distribution and
      quality control. Capital expenditure to support the establishment of facilities
      for laboratory testing, packaging and labelling, filling, formulation and,
      finally, active pharmaceutical ingredient manufacture, approximately US$40
      million in total, had to be secured through loans and grants. According to the
      respondents in the qualitative survey, the principal benefit of the PPP has been
      the uninterrupted supply of vaccines and the ability to respond quickly to
      vaccine shortages. The main disadvantages appear to have been a slow and
      ineffectual establishment of a vaccine manufacturing centre and, initially, a
      limited ability to negotiate highly competitive vaccine prices. CONCLUSIONS:
      Overall, it is concluded that a positive value-for-money has been achieved and
      the institute has been of significant public benefit. Relationships of this
      nature can be used to achieve public health goals, but need to be realistic about
      timeframes, costs and the limitations of relational governance in ensuring that
      complex programmatic outcomes are achieved. It is recommended that a more
      incremental approach, with clearer contractual goals, penalties and incentives,
      is adopted in attempting initiatives aimed at the localisation of manufacturing
      technology by leveraging public procurement.

PMID- 29587778
TI  - HPV genotype determination and E6/E7 mRNA detection for management of HPV
      positive women.
AB  - BACKGROUND: Clinical management of HPV positive women is difficult since many of
      the infections, including high-risk oncogene genotypes (hr-HPV), are transient.
      Therefore only a limited number of patients have a high-grade lesion and sending
      all HPV positive women for colposcopy would only increase costs and unnecessary
      treatment, with serious psychological consequences for patients. The need has
      emerged to identify other HPV related markers able to correctly detect women with
      a high-risk of developing high-grade lesions. Genotyping and the search for E6/E7
      mRNA are among the possible candidates. METHODS: The study was carried out by
      means of an observational analysis of the data relative to 674 HR-HPV positive
      women who we had observed from January 2013 to June 2015; the data had been
      gathered in a database at the HPV Center of the University Hospital of Catania,
      Italy. Women were considered eligible for this study if the following data was
      present in the database: Pap TEST, histologic evaluation, HPV TEST and E6/E7 mRNA
      detection. We calculated the Odds Ratio (OR) of woman who were mRNA positive,
      with CIN2+ lesions, and Odds Ratio of HPV16 positive women. RESULTS: Transcripts
      were detected in 23.6% (69/292) of the women with CIN1 and in 97.2% (210/220) of
      those with CIN2 + . Regarding genotyping, the 81,8% (180/220) of the women with
      CIN2+ had genotype 16, while only 18.1% (40/220) had genotype 18, 31, 33, 45. We
      calculated the OR in the group of HPV16 women with CIN2+ (OR = 4.62; 95% CI =
      3.13 to 6.82), this value increased (OR = 106.12; 95% CI = 53.71 to 209.69) in
      women with CIN2+ and positive mRNA. DISCUSSION: The presence of the HPV16
      genotype in our study was associated with a risk 5 times greater of developing a
      high-grade lesion (CIN2+) (OR = 4.62 95% CI:3.13-6.82); this supports the
      hypothesis that it would be opportune to have targeted protocols for the
      management of HPV 16 positive women. The results showed that there was an
      association between E6/E7 mRNA expression and histology (OR = 106.12; 95% CI =
      53.71 to 209.69). The E6/E7 mRNA test showed a higher prevalence of E6 and E7
      transcripts in patients with higher-grade lesions. CONCLUSION: The results of
      this study suggest that the HPV genotype determination and E6/E7 mRNA detection
      would find an important application for management of HPV positive women.

PMID- 29587779
TI  - A novel cardiovirus in wild rats.
AB  - BACKGROUND: Cardioviruses cause severe illnesses in rodents and humans. In recent
      years, novel cardioviruses have been frequently found, which promoted further
      studies of the genetic diversity of cardioviruses. Using viral metagenomics, we
      genetically characterized a novel cardiovirus (named SX1) from wild rat feces.
      The genomic structure of SX1 shared similar features with those of the Theiler's
      murine encephalomyelitis viruses, including a leader protein, four structural
      proteins and seven non-structural proteins. Phylogenetic analysis based on both
      structural proteins and non-structural proteins coding regions showed that SX1
      was formed into a separate branch, being located between the branches of
      Theiler's murine encephalomyelitis viruses and Thera viruses. Variable resides
      presented in the Ser/Thr rich domain of L protein, VP1 loops, and VP2 puffs
      distinguished SX1 from Theiler's murine encephalomyelitis viruses, suggesting the
      different antigenicity and pathogenicity of SX1.

PMID- 29587780
TI  - Genotype-specific and cross-reactive neutralizing antibodies induced by dengue
      virus infection: detection of antibodies with different levels of neutralizing
      activities against homologous and heterologous genotypes of dengue virus type 2
      in common marmosets (Callithrix jacchus).
AB  - BACKGROUND: A vaccine against all four dengue virus (DENV) serotypes includes the
      formulation of one genotype of each serotype. Although genetic similarities among
      genotypes within a serotype are higher as compared to those among serotypes,
      differences in the immunogenicity of the included genotypes would be a critical
      issue in maximizing successful dengue vaccine development. Thus, we determined
      the neutralizing antibody responses against three genotypes of dengue virus
      serotype 2 (DENV-2), namely Cosmopolitan, Asian I, and Asian/American, after
      primary and secondary inoculation with DENV-2 in a dengue animal model, the
      common marmoset (Callithrix jacchus). METHODS: A total of fifty-four plasma
      samples were obtained from thirty-four marmosets that were inoculated with
      clinically-isolated DENV strains or DENV candidate vaccines, were used in this
      study. Plasma samples were obtained from marmosets after primary inoculation with
      DENV-2 infection, secondary inoculation with homologous or heterologous
      genotypes, and tertiary inoculation with heterologous DENV. Neutralizing antibody
      titers against DENV-2 (Cosmopolitan, Asian I, and Asian/American genotypes) and
      DENV-1 were determined using a conventional plaque reduction neutralization
      assay. RESULTS: In marmosets that were inoculated with the Cosmopolitan genotype
      in primary infection, neutralizing antibody neutralized 3 genotypes, and the
      titers to Asian I genotype were significantly higher than those to homologous
      Cosmopolitan genotype. After secondary DENV-2 infection with heterologous
      genotype (Asian I in primary and Asian/American in secondary), neutralizing
      antibody titers to Asian/American genotype was significantly higher than those
      against Cosmopolitan and Asian I genotypes. Following tertiary infection with
      DENV-1 following DENV-2 Asian I and Cosmopolitan genotypes, neutralizing antibody
      titers to Asian/American were also significantly higher than those against
      Cosmopolitan and Asian I genotypes. CONCLUSION: The present study demonstrated
      that different levels of neutralizing antibodies were induced against variable
      DENV-2 genotypes after primary, secondary and tertiary infections, and that
      neutralizing antibody titers to some heterologous genotypes were higher than
      those to homologous genotypes within a serotype. The results indicate that
      heterogeneity and homogeneity of infecting genotypes influence the levels and
      cross-reactivity of neutralizing antibodies induced in following infections. The
      results also suggest that certain genotypes may possess advantage in terms of
      breakthrough infections against vaccination.

PMID- 29587781
TI  - Ossifying Fibromyxoid tumor of soft parts in head and neck: case report and
      literature review.
AB  - BACKGROUND: Ossifying fibromyxoid tumor of soft parts (OFMT), is a rare but
      morphologically distinctive neoplasm of uncertain histogenesis that most
      frequently affects middle-aged male adults. Clinically, it usually presents as a
      slowly enlarging, small, circumscribed mass, which in most cases is painless.
      OFMT is most frequently found within the subcutaneous tissues of extremities or
      trunk, and rarely in the oral/head and neck region. We present an unusual case of
      this tumor in the submandibular region, and, based on the current medical
      literatures this is probably the first case described in this anatomical
      location. CASE PRESENTATION: A 32-year-old male presented to our outpatient
      clinic with a right submandibular mass with 1-year of evolution. Excisional
      biopsy showed that it was characterized by ossification along the periphery of
      the lesion. The neoplastic cells were spindle-like with scant eosinophilic
      cytoplasm. These cells were arranged with uniform cell-to-cell space in a
      fibromyxoid stroma. Small and large clusters of calcifications were present
      within the tumor. Immunohistochemically, the case showed positive staining of S
      100 protein, vimentin, nestin, calponin, SMA, GFAF, desmin, INI-1, caldesmon, and
      CD34. It also showed negative staining of CK, CK7, CK8/18, NF, and EMA. About 2%
      of neoplastic cells showed positive staining of Ki67. Based on these features,
      the final pathological diagnosis was OFMT. CONCLUSIONS: It is hoped that a
      greater understanding of OFMT in the head and neck region will avoid potential
      misdiagnosis, and contribute to determining the correct management, which appears
      to be complete surgical excision with close follow-up for recurrence
      surveillance.

PMID- 29587782
TI  - Knowledge-based IMRT planning for individual liver cancer patients using a novel
      specific model.
AB  - BACKGROUND: The purpose of this work is to benchmark RapidPlan against clinical
      plans for liver Intensity-modulated radiotherapy (IMRT) treatment of patients
      with special anatomical characteristics, and to investigate the prediction
      capability of the general model (Model-G) versus our specific model (Model-S).
      METHODS: A library consisting of 60 liver cancer patients with IMRT planning was
      used to set up two models (Model-S, Model-G), using the RapidPlan knowledge-based
      planning system. Model-S consisted of 30 patients with special anatomical
      characteristics where the distance from planning target volume (PTV) to the right
      kidney was less than three centimeters and Model-G was configurated using all 60
      patients in this library. Knowledge-based IMRT plans were created for the
      evaluation group formed of 13 patients similar to those included in Model-S by
      Model-G, Model-S and manually (M), named RPG-plans, RPS-plans and M-plans,
      respectively. The differences in the dose-volume histograms (DVHs) were compared,
      not only between RP-plans and their respective M-plans, but also between RPG
      plans and RPS-plans. RESULTS: For all 13 patients, RapidPlan could automatically
      produce clinically acceptable plans. Comparing RP-plans to M-plans, RP-plans
      improved V95% of PTV and had greater dose sparing in the right kidney. For the
      normal liver, RPG-plans delivered similar doses, while RPS-plans delivered a
      higher dose than M-plans. With respect to RapidPlan models, RPS-plans had better
      conformity index (CI) values and delivered lower doses to the right kidney V20Gy
      and maximizing point doses to spinal cord, while delivering higher doses to the
      normal liver. CONCLUSION: The study shows that RapidPlan can create high-quality
      plans, and our specific model can improve the CI of PTV, resulting in more
      sparing of OAR in IMRT for individual liver cancer patients.

PMID- 29587783
TI  - Worldwide use of the first set of physical activity Country Cards: The Global
      Observatory for Physical Activity - GoPA!
AB  - BACKGROUND: The work of The Global Observatory for Physical Activity-GoPA! is the
      first global effort to compile standardized country-level surveillance, policy
      and research data for physical activity in order to better understand how
      countries and regions address promoting physical activity. GoPA! developed
      standardized country-specific physical activity profiles ("Country Cards") to
      summarize country-level data through 2013. The aim of this study was to assess
      use of the Country Cards, identify the factors associated with their use, and
      develop recommendations for supporting country-level physical activity promotion.
      METHODS: Cross sectional internet-based survey conducted between August-October
      2016. Target study participants were national physical activity leaders and
      advocates in academia, government and practice from the GoPA! countries, and
      members of the International Society of Physical Activity and Health. A Country
      Card use composite score was created based on the diversity and frequency of use.
      Statistical analyses on the associations between the composite score and
      respondent characteristics, country characteristics, barriers and opinions were
      conducted (including descriptive analyses and a logistic regression with robust
      standard errors). RESULTS: One hundred forty three participants from 68 countries
      completed the survey. Use of the Country Cards was associated with being part of
      the GoPA! network, knowing about the Country Cards, and on the stage of country
      capacity for physical activity promotion. Country Card knowledge varied by
      country income group, region and the country specific context. More diverse and
      frequent use of the cards (highest tertile of the composite score for use) was
      associated with: 1. Being a country contact vs general participant (OR 18.32-95%
      CI 5.63-59.55, p = 0.002), and 2. Collaborating with a government representative
      working in NCDs on a monthly or more frequent contact vs less frequent contact
      (OR 3.39-95% CI 1.00-11.54, P < 0.05). CONCLUSIONS: For the Country Cards to have
      a broader impact, GoPA! will need to widen its reach beyond the academic sector.
      With further refinement of the cards, and training in their implementation, they
      could be an important tool for advancing country capacity for contextually
      relevant strategies, actions and timelines for PA promotion.

PMID- 29587784
TI  - Mesh-reinforced pancreaticojejunostomy versus conventional pancreaticojejunostomy
      after pancreaticoduodenectomy: a retrospective study of 126 patients.
AB  - BACKGROUND: Pancreatic fistula is a major cause of morbidity and mortality after
      pancreaticoduodenectomy. The aim of this study is to compare the safety and
      efficacy of a newly developed technique, namely mesh-reinforced
      pancreaticojejunostomy, in comparison with the conventional use of
      pancreaticojejunostomy after undergoing a pancreaticoduodenectomy. METHODS: Data
      was collected from regarding 126 consecutive patients, who underwent the mesh
      reinforced pancreaticojejunostomy or conventional pancreaticojejunostomy, after
      standard pancreaticoduodenectomy by one group of surgeons, between the time
      period of 2005 and 2016. This data was collected retrospectively. Surgical
      parameters and perioperative outcomes were compared between these two groups.
      RESULTS: A total of 65 patients received mesh-reinforced pancreaticojejunostomy
      and 61 underwent conventional pancreaticojejunostomy. There were no substantial
      differences in surgical parameters, mortality, biliary leakage, delayed gastric
      emptying, gastrojejunostomy leakage, intra-abdominal fluid collection,
      postpancreatectomy hemorrhage, reoperation, and the total hospital costs between
      the two groups. Pancreatic fistula rate (15 versus 34%; p = 0.013), overall
      surgical morbidity (25 versus 43%; p = 0.032), and length of hospital stay (18 +/
      9 versus 23 +/- 12 days; p = 0.016) were significantly reduced after mesh
      reinforced pancreaticojejunostomy. Multivariate analysis of the postoperative
      pancreatic fistula revealed that the independent factors that were highly
      associated with pancreatic fistula were a soft pancreatic texture and the type of
      conventional pancreaticojejunostomy. CONCLUSIONS: This retrospective single
      center study showed that mesh-reinforced pancreaticojejunostomy appears to be a
      safe technique for pancreaticojejunostomy. It may reduce pancreatic fistula rate
      and surgical complications after pancreaticoduodenectomy. TRIAL REGISTRATION:
      This research is waivered from trial registration because it is a retrospective
      analysis of medical records.

PMID- 29587785
TI  - Trigger wrist caused by avascular necrosis of the capitate: a case report.
AB  - BACKGROUND: Trigger wrist is a rare condition first described by Marti in 1960,
      and various causes have been reported. The condition mostly occurs with finger
      flexion and extension, and rarely with flexion and extension of the wrist itself.
      Avascular necrosis of the capitate is also a rare condition, first described by
      Jonsson in 1942. While some reports of this condition have been published, little
      is known about its etiology. Therefore, no established treatment exists. We
      report a case of trigger wrist caused by avascular necrosis of the capitate. CASE
      PRESENTATION: A 16-year-old right-handed male who was a high school handball
      player was referred to our department from a nearby hospital 5 months after the
      onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At
      the previous hospital, imaging findings led to a diagnosis of avascular necrosis
      of the capitate, and conservative treatment with a wrist brace did not improve
      the pain. At the initial visit to our department, the patient was noted to have a
      painful trigger wrist that was brought on by wrist flexion and extension.
      Preoperative imaging findings led to a diagnosis of trigger wrist caused by
      capitolunate instability secondary to avascular necrosis of the capitate. We
      performed a partial excision of the proximal capitate with tendon ball
      interposition. Two years after surgery, the patient's clinical outcome was
      favorable, with no recurrence of wrist pain or triggering. CONCLUSIONS: Both
      trigger wrist and avascular necrosis of the capitate are rare disorders. When a
      patient presents with painful triggering at the wrist, surgeons must bear in mind
      that avascular necrosis of the capitate may result in this phenomenon. We
      recommend partial excision of the proximal capitate with tendon ball
      interposition for the treatment of this lesion.

PMID- 29587786
TI  - Effects of the S42 residue of the H1N1 swine influenza virus NS1 protein on
      interferon responses and virus replication.
AB  - BACKGROUND: The influenza A virus non-structural protein 1 (NS1) is a
      multifunctional protein that plays an important role in virus replication,
      virulence and inhibition of the host antiviral immune response. In the avian
      influenza virus or human influenza virus, specific amino acids of NS1 have been
      shown to be important for the virus to antagonize host antiviral defenses and
      promote viral replication. However, little research has been reported regarding
      the swine influenza virus (SIV) NS1 protein. METHODS: To study the effects of the
      key amino acids of NS1, we rescued NS1 mutants (S42P, D92E, and S42P/D92E) of the
      A/swine/Shanghai/3/2014(H1N1) strain and compared their replication ability and
      cytokine production as well as the intracellular localization in cultured cells.
      RESULTS: We found that the S42P and D92E mutation displayed no changes on NS1
      nuclear localization. The S42P (but not D92E) mutation suppressed protein
      synthesis and reduced virus growth properties, and there was an inability to
      antagonize host cell interferon production and IRF3 activation, which led to high
      levels of IFN-alpha and IFN-beta production. CONCLUSION: We conclude that the S42
      residue of the NS1 of the A/swine/Shanghai/3/2014(H1N1) strain is the key amino
      acid in regulating the host IFN response by blocking the activation of IRF3 and
      thus facilitates virus replication.

PMID- 29587787
TI  - Pediatric Langerhans cell histiocytosis of the temporal bone: clinical and
      imaging studies of 27 cases.
AB  - BACKGROUND: We aimed to evaluate the clinical and imaging presentations of
      Langerhans cell histiocytosis (LCH) in the pediatric temporal bone. METHODS: This
      retrospective study included 27 pediatric cases with pathological confirmed LCH
      of the temporal bone. The clinical and imaging features of the cases were
      analyzed. The involvement of ossicular chain and otic capsule was also evaluated.
      RESULTS: A total of 38 lesions (27 cases) with 11 bilateral involvement were
      identified. For the 27 cases, the most common complaint was periauricular
      swelling (12/27, 44.4%), followed by otorrhea (9/27, 33.3%) and otalgia (5/27,
      18.2%). The mastoid process was the most common involved subsite (31/38, 81.6%)
      among the 38 lesions. Ten (26.3%, 10/38) lesions belonged to the group of the
      diffuse involvement, 22 (57.9%, 22/38) were divided into the group of partial
      involvement and six (15.8%,6/38) localized lesions with punched-out appearance.
      Erosion of ossicular chains and otic capsule were found in three and seven
      lesions respectively. CONCLUSION: The results indicate that the most common
      subsite for LCH of the pediatric temporal bone was the mastoid process. The
      location and extent of pediatric LCH of the temporal bone varied a lot between
      each other. The ossicular chains usually remain intact and the erosion of otic
      capsule can occur in some lesions.

PMID- 29587788
TI  - Socioeconomic inequalities in cardiometabolic control in patients with type 2
      diabetes.
AB  - BACKGROUND: The aim of this study was to determine if the achievement of control
      targets in patients with type 2 diabetes was associated with personal
      socioeconomic factors and if these associations were sex-dependent. METHODS: This
      cross-sectional, population-based study was conducted in Spain. Glycated
      haemoglobin (HbA1c) level and other clinical parameters were obtained from
      electronic primary care records (n = 32,638 cases). Socioeconomic status was
      determined using education level and yearly income. Among patients, having their
      HbA1c level checked during the previous year was considered as an indirect
      measure of the process of care, whereas tobacco use and clinical parameters such
      as HbA1c, low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP)
      were considered intermediate control outcomes. General linear mixed effect models
      were used to assess associations. RESULTS: The achievement of metabolic and
      cardiovascular control targets in patients with type 2 diabetes was associated
      with educational level and income, and socioeconomic gradients differed by sex.
      The probability of having had an HbA1c test performed in the previous year was
      higher in patients with lower education levels. Patients in the lowest income and
      education level categories were less likely to have reached the recommended HbA1c
      level. Males in the lowest education level categories were less likely to be non
      smokers or to have achieved the blood pressure targets. In contrast, patients
      within the low income categories had a higher probability of reaching the
      recommended LDL-c level. CONCLUSIONS: Our results suggest the presence of
      socioeconomic inequalities in the achievement of cardiovascular and metabolic
      control that differed in direction and magnitude depending on the measured
      outcome and sex of the patient. These findings may help health professionals
      focus on high-risk individuals to decrease health inequalities.

PMID- 29587790
TI  - Inhibition of HIV early replication by the p53 and its downstream gene p21.
AB  - BACKGROUND: The tumor suppressor gene p53 has been found to suppress HIV
      infection by various mechanisms, but the inhibition of HIV at an early stage of
      replication by host cell p53 and its downstream gene p21 has not been well
      studied. METHOD: VSV-G pseudotyped HIV-1 or HIV-2 viruses with GFP or luciferase
      reporter gene were used to infect HCT116 p53+/+ cells, HCT116 p53-/- cells and
      hMDMs. The infections were detected by flow cytometry or measured by luciferase
      assay. Reverse transcription products were quantified by a TaqMan real time PCR.
      siRNA knockdown experiments were applied to study potential roles of p53 and p21
      genes in their restriction to HIV infection. Western blot experiments were used
      to analyze changes in gene expression. RESULTS: The infection of HIV-1 was
      inhibited in HCT116 p53+/+ cells in comparison to HCT116 p53-/- cells. The fold
      of inhibition was largely increased when cell cycle switched from cycling to non
      cycling status. Further analysis showed that both p53 and p21 expressions were
      upregulated in non-cycling HCT116 p53+/+ cells and HIV-1 reverse transcription
      was subsequently inhibited. siRNA knockdown of either p53 or p21 rescued HIV-1
      reverse transcription from the inhibition in non-cycling HCT116 p53+/+ cells. It
      was identified that the observed restrictions by p53 and p21 were associated with
      the suppression of RNR2 expression and phosphorylation of SAMHD1. These
      observations were confirmed by using siRNA knockdown experiments. In addition,
      p53 also inhibited HIV-2 infection in HCT116 p53+/+ cells and siRNA knockdown of
      p21 increased HIV-2 infection in hMDMs. Finally the expressions of p53 and p21
      were found to be induced in hMDMs shortly after HIV-1 infection. CONCLUSIONS: The
      p53 and its downstream gene p21 interfere with HIV early stage of replication in
      non-cycling cells and hMDMs.

PMID- 29587789
TI  - Rescue and characterization of recombinant cedar virus, a non-pathogenic
      Henipavirus species.
AB  - BACKGROUND: Hendra virus and Nipah virus are zoonotic viruses that have caused
      severe to fatal disease in livestock and human populations. The isolation of
      Cedar virus, a non-pathogenic virus species in the genus Henipavirus, closely
      related to the highly pathogenic Hendra virus and Nipah virus offers an
      opportunity to investigate differences in pathogenesis and receptor tropism among
      these viruses. METHODS: We constructed full-length cDNA clones of Cedar virus
      from synthetic oligonucleotides and rescued two replication-competent,
      recombinant Cedar virus variants: a recombinant wild-type Cedar virus and a
      recombinant Cedar virus that expresses a green fluorescent protein from an open
      reading frame inserted between the phosphoprotein and matrix genes. Replication
      kinetics of both viruses and stimulation of the interferon pathway were
      characterized in vitro. Cellular tropism for ephrin-B type ligands was
      qualitatively investigated by microscopy and quantitatively by a split-luciferase
      fusion assay. RESULTS: Successful rescue of recombinant Cedar virus expressing a
      green fluorescent protein did not significantly affect virus replication compared
      to the recombinant wild-type Cedar virus. We demonstrated that recombinant Cedar
      virus stimulated the interferon pathway and utilized the established Hendra virus
      and Nipah virus receptor, ephrin-B2, but not ephrin-B3 to mediate virus entry. We
      further characterized virus-mediated membrane fusion kinetics of Cedar virus with
      the known henipavirus receptors ephrin-B2 and ephrin-B3. CONCLUSIONS: The
      recombinant Cedar virus platform may be utilized to characterize the determinants
      of pathogenesis across the henipaviruses, investigate their receptor tropisms,
      and identify novel pan-henipavirus antivirals. Moreover, these experiments can be
      conducted safely under BSL-2 conditions.

PMID- 29587791
TI  - Sexual and reproductive health behavior and unmet needs among a sample of
      adolescents living with HIV in Zambia: a cross-sectional study.
AB  - BACKGROUND: Adolescents living with HIV face challenges, such as disclosure of
      HIV status, adherence to antiretroviral therapy, mental health, and sexual and
      reproductive health (SRH). These challenges affect their future quality of life.
      However, little evidence is available on their sexual behaviors and SRH needs in
      Zambia. This study aimed at assessing their sexual behaviors and SRH needs and
      identifying factors associated with marriage concerns and a desire to have
      children. METHODS: This cross-sectional study was conducted at the University
      Teaching Hospital from April to July 2014. We recruited 200 adolescents aged 15
      19 years who were aware of their HIV-positive status. We collected data on their
      first and recent sexual behavior, concerns about marriage, and desire to have
      children. We used the Generalized Linear Model to identify factors associated
      with having concerns about marriage and desire to have children. We performed
      thematic analysis with open-ended data to determine their perceptions about
      marriage and having children in the future. RESULTS: Out of 175 studied
      adolescents, 20.6% had experienced sexual intercourse, and only 44.4% used
      condoms during the first intercourse. Forty-eight percent had concerns about
      marriage, and 87.4% desired to have children. Marriage-related concerns were high
      among those who desired to have children (adjusted relative risk [ARR] = 2.51,
      95% CI = 1.02 to 6.14). Adolescents who had completed secondary school were more
      likely to desire to have children (ARR = 1.35, 95% CI = 1.07 to 1.71).
      Adolescents who had lost both parents were less likely to want children (ARR =
      0.80, 95% CI = 0.68 to 0.95). Thematic analysis identified that major concerns
      about future marriage were fear of disclosing HIV status to partners and risk of
      infecting partners and/or children. The reasons for their willingness to have
      children were the desire to be a parent, having children as family assets, a
      human right, and a source of love and happiness. CONCLUSIONS: Zambian adolescents
      living with HIV are at risk of engaging in risky sexual relationships and have
      difficulties in meeting needs of SRH. HIV care service must respond to a wide
      range of needs.

PMID- 29587792
TI  - Major contribution of the RNA-binding domain of NS1 in the pathogenicity and
      replication potential of an avian H7N1 influenza virus in chickens.
AB  - BACKGROUND: Non-structural protein NS1 of influenza A viruses harbours several
      determinants of pathogenicity and host-range. However it is still unclear to what
      extent each of its two structured domains (i.e. RNA-binding domain, RBD, and
      effector domain, ED) contribute to its various activities. METHODS: To evaluate
      the respective contributions of the two domains, we genetically engineered two
      variants of an H7N1 low pathogenicity avian influenza virus harbouring amino-acid
      substitutions that impair the functionality of either domain. The RBD- and ED
      mutant viruses were compared to their wt- counterpart in vivo and in vitro,
      notably in chicken infection and avian cell culture models. RESULTS: The double
      substitution R38A-K41A in the RBD dramatically reduced the pathogenicity and
      replication potential of the virus, whereas the substitution A149V that was
      considered to abrogate the IFN-antagonistic activity of the effector domain
      entailed much less effects. While all three viruses initiated the viral life
      cycle in avian cells, replication of the R38A-K41A virus was severely impaired.
      This defect was associated with a delayed synthesis of nucleoprotein NP and a
      reduced accumulation of NS1, which was found to reach a concentration of about 30
      micromol.L- 1 in wt-infected cells at 8 h post-infection. When overexpressed in
      avian lung epithelial cells, both the wt-NS1 and 3841AA-NS1, but not the A149V
      NS1, reduced the poly(I:C)-induced activation of the IFN-sensitive chicken Mx
      promoter. Unexpectedly, the R38A-K41A substitution in the recombinant RBD did not
      alter its in vitro affinity for a model dsRNA. When overexpressed in avian cells,
      both the wt- and A149V-NS1s, as well as the individually expressed wt-RBD to a
      lesser extent, enhanced the activity of the reconstituted viral RNA-polymerase in
      a minireplicon assay. CONCLUSIONS: Collectively, our data emphasized the critical
      importance and essential role of the RNA-binding domain in essential steps of the
      virus replication cycle, notably expression and translation of viral mRNAs.

PMID- 29587793
TI  - Thriving in scrubs: a qualitative study of resident resilience.
AB  - BACKGROUND: Physician well-being impacts both doctors and patients. In light of
      high rates of physician burnout, enhancing resilience is a priority. To inform
      effective interventions, educators need to understand how resilience develops
      during residency. METHODS: A qualitative study using grounded theory examined the
      lived experience of resilience in residents. A cohort of obstetrics and
      gynecology residents were selected as a purposive, intensity sample.. Eighteen
      residents in all years of training participated in semi-structured interviews. A
      three-phase process of open coding, analytic coding and thematic analysis
      generated a conceptual model for resilience among residents. RESULTS: Resilience
      among residents emerged as rooted in the resident's calling to the work of
      medicine. Drive to overcome obstacles arose from personal identity and aspiration
      to professional ideals. Adversity caused residents to examine and cultivate
      coping mechanisms. Personal connections to peers and mentors as well as to
      patients and the work helped buffer the stress and conflicts that present.
      Resilience in this context is a developmental phenomenon that grows through
      engagement with uncertainty and adversity. CONCLUSION: Resilience in residents is
      rooted in personal and professional identity, and requires engagement with
      adversity to develop. Connections within the medical community, finding personal
      fulfillment in the work, and developing self-care practices enhance resilience.

PMID- 29587794
TI  - The relevance of spatial aggregation level and of applied methods in the analysis
      of geographical distribution of cancer mortality in mainland Portugal (2009
      2013).
AB  - BACKGROUND: Knowledge regarding the geographical distribution of diseases is
      essential in public health in order to define strategies to improve the health of
      populations and quality of life. The present study aims to establish a
      methodology to choose a suitable geographic aggregation level of data and an
      appropriated method which allow us to analyze disease spatial patterns in
      mainland Portugal, avoiding the "small numbers problem." Malignant cancer
      mortality data for 2009-2013 was used as a case study. METHODS: To achieve our
      aims, we used official data regarding the mortality by all malignant cancer,
      between 2009 and 2013, and the mainland Portuguese resident population in 2011.
      Three different spatial aggregation levels were applied: Nomenclature of
      Territorial Units for Statistics, level III (28 areas), municipalities (278
      areas), and parishes (4050 areas). Standardized Mortality Ratio (SMR) and
      relative risk (RR) were computed with Besag, York and Mollie model (BYM) for the
      evaluation of geographic patterns of mortality data. We also estimated Global
      Moran's I, Local Moran's I, and posterior probability (PP) for the spatial
      cluster analysis. RESULTS: Our results show that the occurrence of lower and
      higher extreme values of the standardized mortality ratio tend to increase with
      the decrease of data spatial aggregation. In addition, the number of local
      clusters is higher at small spatial aggregation levels, although the area of each
      cluster is generally smaller. Regarding global clustering, data forms clusters at
      all considered levels. Relative risk (RR) computed by Besag, York and Mollie
      model, in turn, also shows different results at the municipalities and parishes
      levels. However, the difference is smaller than the difference obtained by SMR
      computation. This statement is supported by the coefficient variation values.
      CONCLUSIONS: Our findings show that the choice of spatial data aggregation level
      has high importance in the research results, as different aggregation levels can
      lead to distinct results. In terms of the case study, we conclude that for the
      period of 2009-2013, cancer mortality in mainland Portugal formed clusters. The
      most suitable applicable spatial scale and method seemed to be at the
      municipalities level and Besag, York and Mollie model, respectively. However,
      further studies should be conducted in order to provide greater support to these
      results.

PMID- 29587795
TI  - Clinical outcome after particle therapy for meningiomas of the skull base:
      toxicity and local control in patients treated with active rasterscanning.
AB  - BACKGROUND: Meningiomas of the skull base account for 25-30% of all meningiomas.
      Due to the complex structure of the cranial base and its close proximity to
      critical structures, surgery is often associated with substantial morbidity.
      Treatment options include observation, aggressive surgical intervention,
      stereotactic or conventional radiotherapy. In this analysis we evaluate the
      outcome of 110 patients with meningiomas of the skull base treated with particle
      therapy. It was performed within the framework of the "clinical research group
      heavy ion therapy" and supported by the German Research Council (DFG, KFO 214).
      METHODS: Between May 2010 and November 2014, 110 Patients with skull base
      meningioma were treated with particle radiotherapy at the Heidelberg Ion Therapy
      Center (HIT). Primary localizations included the sphenoid wing (n = 42),
      petroclival region (n = 23), cavernous sinus (n = 4), sella (n = 10) and
      olfactory nerve (n = 4). Sixty meningiomas were benign (WHO  degrees I); whereas
      8 were high-risk (WHO  degrees II (n = 7) and  degrees III (n = 1)). In 42 cases
      histology was not examined, since no surgery was performed. Proton (n = 104) or
      carbon ion (n = 6) radiotherapy was applied at Heidelberg Ion Therapy Center
      (HIT) using raster-scanning technique for active beam delivery. Fifty one
      patients (46.4%) received radiotherapy due to tumor progression, 17 (15.5%) after
      surgical resection and 42 (38.2%) as primary treatment. RESULTS: Median follow-up
      in this analysis was 46,8 months (95% CI 39,9-53,7; Q1-Q3 34,3-61,7). Particle
      radiotherapy could be performed safely without toxicity-related interruptions. No
      grade IV or V toxicities according to CTCAE v4.0 were observed. Particle RT
      offered excellent overall local control rates with 100% progression-free survival
      (PFS) after 36 months and 96.6% after 60 months. Median PFS was not reached due
      to the small number of events. Histology significantly impacted PFS with superior
      PFS after 5 years for low-risk tumors (96.6% vs. 75.0%, p = 0,02). Overall
      survival was 96.2% after 60 months and 92.0% after 72 months from therapy. Of six
      documented deaths, five were definitely not and the sixth probably not meningioma
      related. CONCLUSION: Particle radiotherapy is an excellent treatment option for
      patients with meningiomas of the skull base and can lead to long-term tumor
      control with minimal side effects. Other prospective studies with longer follow
      up will be necessary to further confirm the role of particle radiotherapy in
      skull base meningioma.

PMID- 29587796
TI  - Human papilloma virus correlates of high grade cervical dysplasia in HIV-infected
      women in Mombasa, Kenya: a cross-sectional analysis.
AB  - BACKGROUND: Women living with HIV are at increased risk to be co-infected with
      HPV, persistent high-risk (HR) human papillomavirus (HPV) infection and increased
      HR HPV viral load, which make them more at risk for cervical cancer. Despite
      their inherent vulnerability, there is a scarcity of data on potential high risk
      (pHR) and HR HPV genotypes in HIV- infected women with cervical dysplasia and HPV
      type specific viral load in this population in Sub Saharan Africa. The aim of
      this analysis of HIV-infected women was to explore the virological correlates of
      high-grade cervical dysplasia (CIN 2+) in HIV-infected women, thereby profiling
      HPV genotypes. METHOD: This analysis assesses baseline data obtained from a
      cohort study of 74 HIV-infected women with abnormal cytology attending a
      Comprehensive Care Centre for patients with HIV infection in Mombasa, Kenya.
      Quantitative real-time PCR was used for HPV typing and viral load. RESULTS: CIN 2
      was observed in 16% (12/74) of women, CIN 3 in 23% (17/74), and, invasive
      cervical carcinoma (ICC) in 1% (1/74) of women. In women with CIN 3+, HPV 16
      (44%), HPV 56 (33%), HPV 33 and 53 (HPV 53 (28%) were the most prevalent
      genotypes. HPV 53 was observed as a stand-alone HPV in one woman with ICC. A
      multivariate logistic regression adjusting for age, CD4 count and HPV co
      infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted
      odds ratio [aOR]:4.9; p = 0.05; 95% (Confidence Interval) [CI]:1.03-22.5). Women
      with CIN2+ had a significantly higher viral log mean of HPV 16, (11.2 copies/
      10,000 cells; 95% CI: 9.0-13.4) than with CIN 1. CONCLUSION: The high prevalence
      of HPV 53 in CIN 3 and as a stand-alone genotype in the patient with invasive
      cervical cancer warrants that its clinical significance be further revisited
      among HIV-infected women. HPV 31, along with elevated means of HPV 16 viral load
      were predictors of CIN 2 + .

PMID- 29587797
TI  - Comparison of efficacy and safety of preoperative Chemoradiotherapy in locally
      advanced upper and middle/lower rectal cancer.
AB  - BACKGROUND: We aimed to explore the efficacy and safety profile of preoperative
      neoadjuvant chemoradiation (NACRT) in locally advanced rectal cancer (LARC) in
      upper rectum versus middle/lower rectum. METHODS: The study included 173 patients
      with stage II or III (T2-4b, N0-2b) LARC who underwent NACRT followed by total
      mesorectal excision (TME) between January 2011 and October 2016. Cox regression,
      log-rank test, and Kaplan-Meier curves were calculated. RESULTS: Among the 173
      patients, 58 had lesions in the upper rectum and 115 patients had lesions in
      middle/lower rectum. In a median follow-up of 35 months (range, 6-73 months), the
      5-year disease-free survival (DFS) and overall survival (OS) were 84% and 88% for
      the patients with upper rectal cancer and 77% and 68% for those with middle/lower
      rectal cancer (P = 0.251 and P = 0.058, respectively). The 5-year DFS (P = 0.012)
      and OS (P = 0.003) were better in the NACRT responders [tumor regression grade
      (TRG) 0 or 1] compared with nonresponders (TRG 2 or 3). The independent
      prognostic factor of favorable response to NACRT was the FOLFOX regimen (P =
      0.004). CONCLUSIONS: Patients with LARC in the upper rectum who underwent NACRT
      followed by TME had similar DFS and a trend toward longer OS, compared with those
      who had middle/lower rectal lesions. Furthermore, FOLFOX may yield superior
      results than fluoropyrimidine based regimen during NACRT. NACRT might be an
      alternative option for patients with LARC in the upper rectum as it has a
      favorable pathological complete response rate and comparable clinical outcomes
      when compared with patients with LARC in middle/lower rectum.

PMID- 29587798
TI  - Inhibition of peripheral macrophages by nicotinic acetylcholine receptor agonists
      suppresses spinal microglial activation and neuropathic pain in mice with
      peripheral nerve injury.
AB  - BACKGROUND: Neuro-immune interaction underlies chronic neuroinflammation and
      aberrant sensory processing resulting in neuropathic pain. Despite the
      pathological significance of both neuroinflammation-driven peripheral
      sensitization and spinal sensitization, the functional relationship between these
      two distinct events has not been understood. METHODS: In this study, we
      determined whether inhibition of inflammatory macrophages by administration of
      alpha4beta2 nicotinic acetylcholine receptor (nAChR) agonists improves
      neuropathic pain and affects microglial activation in the spinal dorsal horn
      (SDH) in mice following partial sciatic nerve ligation (PSL). Expression levels
      of neuroinflammatory molecules were evaluated by RT-qPCR and
      immunohistochemistry, and PSL-induced mechanical allodynia was defined by the von
      Frey test. RESULTS: Flow cytometry revealed that CD11b+ F4/80+ macrophages were
      accumulated in the injured sciatic nerve (SCN) after PSL. TC-2559, a full agonist
      for alpha4beta2 nAChR, suppressed the upregulation of interleukin-1beta (IL
      1beta) in the injured SCN after PSL and attenuated lipopolysaccharide-induced
      upregulation of IL-1beta in cultured macrophages. Systemic (subcutaneous, s.c.)
      administration of TC-2559 during either the early (days 0-3) or middle/late (days
      7-10) phase of PSL improved mechanical allodynia. Moreover, local (perineural,
      p.n.) administration of TC-2559 and sazetidine A, a partial agonist for
      alpha4beta2 nAChR, during either the early or middle phase of PSL improved
      mechanical allodynia. However, p.n. administration of sazetidine A during the
      late (days 21-24) phase did not show the attenuating effect, whereas p.n.
      administration of TC-2559 during this phase relieved mechanical allodynia. Most
      importantly, p.n. administration of TC-2559 significantly suppressed
      morphological activation of Iba1+ microglia and decreased the upregulation of
      inflammatory microglia-dominant molecules, such as CD68, interferon regulatory
      factor 5, and IL-1beta in the SDH after PSL. CONCLUSION: These findings support
      the notion that pharmacological inhibition of inflammatory macrophages using an
      alpha4beta2 nAChR agonist exhibit a wide therapeutic window on neuropathic pain
      after nerve injury, and it could be nominated as a novel pharmacotherapy to
      relieve intractable pain.

PMID- 29587799
TI  - HLA alleles modulate EBV viral load in multiple sclerosis.
AB  - BACKGROUND: The etiopathology of multiple sclerosis (MS) is believed to include
      genetic and environmental factors. Human leukocyte antigen (HLA) alleles, in
      particular,  are associated with disease susceptibility, whereas Epstein Barr
      Virus (EBV) infection has long been suspected to play a role in disease
      pathogenesis. The aim of the present study is to evaluate correlations between
      HLA alleles and EBV infection in MS. METHODS: HLA alleles, EBV viral load (VL)
      and serum anti-EBV antibody titers were evaluated in EBV-seropositive MS patients
      (N = 117) and age- and sex-matched healthy controls (HC; N = 89). RESULTS:
      Significantly higher DNA viral loads (p = 0.048) and EBNA-1 antibody titer (p =
      0.0004) were seen in MS compared to HC. EBV VL was higher in HLA-B*07+ (p = 0.02)
      and HLA-DRB1*15+ (p = 0.02) MS patients, whereas it was lower in HLA-A*02+ (p =
      0.04) subjects. EBV VL was highest in HLA-A*02-/B*07+/DRB1*15+ patients and
      lowest in HLA-A*A02+/B*07-/DRB1*15- individuals (p < 0.0001). HLA-B*07 resulted
      the most associated allele to EBV VL after multiple regression analysis
      considering altogether the three alleles, (p = 0.0001). No differences were
      observed in anti-EBV antibody titers in relationship with HLA distribution.
      CONCLUSIONS: Host HLA-B*07 allele influence EBV VL in MS. As HLA-class I
      molecules present antigens to T lymphocytes and initiate immune response against
      viruses, these results could support a role for EBV in MS.

PMID- 29587800
TI  - Inhibiting YAP expression suppresses pancreatic cancer progression by disrupting
      tumor-stromal interactions.
AB  - BACKGROUND: Hippo/YAP pathway is known to be important for development, growth
      and organogenesis, and dysregulation of this pathway leads to tumor progression.
      We and others find that YAP is up-regulated in pancreatic ductal adenocarcinoma
      (PDAC) and associated with worse prognosis of patients. Activated pancreatic
      stellate cells (PSCs) forming the components of microenvironment that enhance
      pancreatic cancer cells (PCs) invasiveness and malignance. However, the role and
      mechanism of YAP in PDAC tumor-stromal interaction is largely unknown. METHODS:
      The expression of YAP in Pancreatic cancer cell lines and PDAC samples was
      examined by Western blot and IHC. The biological role of YAP on cancer cell
      proliferation, epithelial-mesenchymal transition (EMT) and invasion were
      evaluated by MTT, Quantitative real-time PCR analysis, Western blot analysis and
      invasion assay. The effect of YAP on PSC activation was evaluated by PC-PSC co
      culture conditions and xenograft PDAC mouse model. RESULTS: Firstly, knockdown of
      YAP inhibits PDAC cell proliferation and invasion in vitro. In addition, YAP
      modulates the PC and PSC interaction via reducing the production of connective
      tissue growth factor (CTGF) from PCs, inhibits paracrine-mediated PSC activation
      under PC-PSC co-culture conditions and in turn disrupts TGF-beta1-mediated tumor
      stromal interactions. Lastly, inhibiting YAP expression prevents tumor growth and
      suppresses desmoplastic reaction in vivo. CONCLUSIONS: These results demonstrate
      that YAP contributes to the proliferation and invasion of PC and the activation
      of PSC via tumor-stromal interactions and that targeting YAP may be a promising
      therapeutic strategy for PDAC treatment.

PMID- 29587801
TI  - Effects of Dangguixu-san on acute lateral ankle sprain: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Ankle sprain is a common musculoskeletal injury. In Korean medicine,
      blood stasis is thought to be the main cause of pain and swelling in patients
      with ankle sprain. Dangguixu-san (DS), a herbal extract, is widely used in Korean
      medicine for the treatment of traumatic ecchymosis and pain by promoting blood
      circulation and relieving blood stasis. However, the effects of DS on ankle
      sprain have not been evaluated in a randomized clinical trial. Here, we describe
      the protocol for a randomized controlled trial that will evaluate the efficacy
      and safety of DS for the treatment of ankle sprain. METHODS/DESIGN: In this
      randomized, double-blinded, placebo-controlled, parallel-arm clinical trial with
      a 1:1 allocation ratio, participants (n = 48) with acute lateral ankle sprain
      (ALAS) that occurred within 72 h before enrollment will be randomly assigned to a
      DS (n = 24) or a placebo (n = 24) group. Both groups will receive acupuncture
      treatment once a day for 5 days a week (excluding Saturday and Sunday) and the
      trial medication (DS/placebo capsule) three times a day for seven consecutive
      days. The primary outcome measure will be pain relief evaluated using a Visual
      Analog Scale (VAS). Secondary outcome measures will include Foot and Ankle
      Outcome Scores (FAOS), edema, European Quality of Life Five-Dimension-Five-Level
      Scale (EQ-5D-5 L) scores, and the number of recurrent ankle sprains. VAS, FAOS,
      edema, and EQ-5D-5 L scores will be recorded before, at the end of, and at 4
      weeks after treatment completion. EQ-5D-5 L scores will be additionally recorded
      at 26 weeks after treatment completion. The number of recurrent ankle sprains
      will be recorded at 4, 8, 12, and 26 weeks after treatment completion.
      DISCUSSION: This study is expected to provide evidence regarding the efficacy,
      safety, and usefulness of DS for the treatment of ALAS. TRIAL REGISTRATION:
      cris.nih.go.kr, registration number: KCT 0002374 . Registered on 11 July, 2017
      and approved by the Ministry of Food and Drug Safety (registration number,
      31244).

PMID- 29587802
TI  - Disrespect and abuse of women during the process of childbirth in the 2015
      Pelotas birth cohort.
AB  - BACKGROUND: The disrespect and abuse of women during the process of childbirth is
      an emergent and global problem and only few studies have investigated this
      worrying issue. The objective of the present study was to describe the prevalence
      of disrespect and abuse of women during childbirth in Pelotas City, Brazil, and
      to investigate the factors involved. METHODS: This was a cross-sectional
      population-based study of women delivering members of the 2015 Pelotas birth
      cohort. Information relating to disrespect and abuse during childbirth was
      obtained by household interview 3 months after delivery. The information related
      to verbal and physical abuse, denial of care and invasive and/or inappropriate
      procedures. Poisson regression was used to evaluate the factors associated with
      one or more, and two or more, types of disrespectful treatment or abuse. RESULTS:
      A total of 4275 women took part in a perinatal study. During the three-month
      follow-up, we interviewed 4087 biological mothers with regards to disrespect and
      abuse. Approximately 10% of women reported having experienced verbal abuse, 6%
      denial of care, 6% undesirable or inappropriate procedures and 5% physical abuse.
      At least one type of disrespect or abuse was reported by 18.3% of mothers (95%
      confidence interval [CI]: 17.2-19.5); and at least two types by 5.1% (95% CI: 4.4
      5.8). Women relying on the public health sector, and those whose childbirths were
      via cesarean section with previous labor, had the highest risk, with
      approximately a three- and two-fold increase in risk, respectively. CONCLUSIONS:
      Our study showed that the occurrence of disrespect and abuse during childbirth
      was high and mostly associated with payment by the public sector and labor before
      delivery. The efforts made by civil society, governments and international
      organizations are not sufficient to restrain institutional violence against women
      during childbirth. To eradicate this problem, it is essential to 1) implement
      policies and actions specific for this type of violence and 2) formulate laws to
      promote the equality of rights between women and men, with particular emphasis on
      the economic rights of women and the promotion of gender equality in terms of
      access to jobs and education.

PMID- 29587803
TI  - Sample size implications of mortality definitions in sepsis: a retrospective
      cohort study.
AB  - BACKGROUND: Many randomized controlled trials (RCTs) employ mortality at a given
      time as a primary outcome. There are at least three common ways to measure 90-day
      mortality: first, all-location mortality, that is, all-cause mortality within 90
      days of randomization at any location. Second, ARDSnet mortality is death in a
      healthcare facility of greater intensity than the patient was in prior to the
      hospitalization during which they were randomized. Finally, in-hospital mortality
      is death prior to discharge from the primary hospitalization of randomization.
      Data comparing the impact of these different measurements on sample size are
      lacking. We evaluated the extent to which event rates vary by mortality
      definition. METHODS: This was a retrospective cohort study of 30,691 patients
      hospitalized at Veterans Affairs (VA) hospitals for sepsis during 2009. 12,727
      (41.5%) received care in an ICU setting. For each patient, we measured event
      rates for three different 90-day mortality outcomes: all-location mortality,
      ARDSnet mortality, and in-hospital mortality. We also calculated sample sizes
      necessary to power an example RCT given those event rates. RESULTS: At 90 days,
      all-location mortality was 26.4% (95% CI 25.9-26.9%), ARDSnet mortality was 19.2%
      (95% CI 18.8-19.7%), and in-hospital mortality was 13.4% (95% CI 13.0-13.8%) (p <
      0.01 all comparisons). These respective event rates result in different required
      sample sizes to achieve a 20% relative reduction in mortality with 80% power and
      a 5% false positive rate. Such a trial of VA sepsis patients would require 2080
      patients for all-location mortality, 3080 for ARDSnet mortality, and 4796 for in
      hospital mortality. Among sepsis patients mechanically ventilated in an ICU, 2438
      experienced all-location mortality (46.2% [95% CI 44.8-47.5%]), 2181 experienced
      ARDSnet mortality (41.3% [95% CI 40.0-42.6%]), and 1894 experienced in-hospital
      mortality (36.0% [95% CI 34.7-37.3%]). CONCLUSIONS: Event rates vary
      substantially in sepsis patients based on the chosen 90-day mortality definition.
      This could have important implications for RCT design trade-offs.

PMID- 29587804
TI  - Developing measures to assess constructs from the Inner Setting domain of the
      Consolidated Framework for Implementation Research.
AB  - BACKGROUND: Scientists and practitioners alike need reliable, valid measures of
      contextual factors that influence implementation. Yet, few existing measures
      demonstrate reliability or validity. To meet this need, we developed and assessed
      the psychometric properties of measures of several constructs within the Inner
      Setting domain of the Consolidated Framework for Implementation Research (CFIR).
      METHODS: We searched the literature for existing measures for the 7 Inner Setting
      domain constructs (Culture Overall, Culture Stress, Culture Effort,
      Implementation Climate, Learning Climate, Leadership Engagement, and Available
      Resources). We adapted items for the healthcare context, pilot-tested the adapted
      measures in 4 Federally Qualified Health Centers (FQHCs), and implemented the
      revised measures in 78 FQHCs in the 7 states (N = 327 respondents) with a focus
      on colorectal cancer (CRC) screening practices. To psychometrically assess our
      measures, we conducted confirmatory factor analysis models (CFA; structural
      validity), assessed inter-item consistency (reliability), computed scale
      correlations (discriminant validity), and calculated inter-rater reliability and
      agreement (organization-level construct reliability and validity). RESULTS: CFAs
      for most constructs exhibited good model fit (CFI > 0.90, TLI > 0.90, SRMR <
      0.08, RMSEA < 0.08), with almost all factor loadings exceeding 0.40. Scale
      reliabilities ranged from good (0.7 <= alpha < 0.9) to excellent (alpha >= 0.9).
      Scale correlations fell below 0.90, indicating discriminant validity. Inter-rater
      reliability and agreement were sufficiently high to justify measuring constructs
      at the clinic-level. CONCLUSIONS: Our findings provide psychometric evidence in
      support of the CFIR Inner Setting measures. Our findings also suggest the Inner
      Setting measures from individuals can be aggregated to represent the clinic
      level. Measurement of the Inner Setting constructs can be useful in better
      understanding and predicting implementation in FQHCs and can be used to identify
      targets of strategies to accelerate and enhance implementation efforts in FQHCs.

PMID- 29587805
TI  - Patient-centered recruitment and retention for a randomized controlled study.
AB  - BACKGROUND: Recruitment and retention strategies for patient-centered outcomes
      research are evolving and research on the subject is limited. In this work, we
      present a conceptual model of patient-centered recruitment and retention, and
      describe the recruitment and retention activities and related challenges in a
      patient-centered comparative effectiveness trial. METHODS: This is a multicenter,
      longitudinal randomized controlled trial in localized prostate cancer patients.
      RESULTS: We recruited 743 participants from three sites over 15 months period
      (January 2014 to March 2015), and followed them for 24 months. At site 1, of the
      773 eligible participants, 551 (72%) were enrolled. At site 2, 34 participants
      were eligible and 23 (68%) enrolled. Of the 434 eligible participants at site 3,
      169 (39%) enrolled. We observed that strategies related to the concepts of trust
      (e.g., physician involvement, ensuring protection of information), communication
      (e.g., brochures and pamphlets in physicians' offices, continued contact during
      regular clinic visits and calling/emailing assessment), attitude (e.g.,
      emphasizing the altruistic value of research, positive attitude of providers and
      research staff), and expectations (e.g., full disclosure of study requirements
      and time commitment, update letters) facilitated successful patient recruitment
      and retention. A stakeholders' advisory board provided important input for the
      recruitment and retention activities. Active engagement, reminders at the
      offices, and personalized update letters helped retention during follow-up.
      Usefulness of telephone recruitment was site specific and, at one site, the time
      requirement for telephone recruitment was a challenge. CONCLUSIONS: We have
      presented multilevel strategies for successful recruitment and retention in a
      clinical trial using a patient-centered approach. Our strategies were flexible to
      accommodate site-level requirements. These strategies as well as the challenges
      can aid recruitment and retention efforts of future large-scale, patient-centered
      research studies. TRIAL REGISTRATION: Clinicaltrials.gov , ID: NCT02032550 .
      Registered on 22 November 2013.

PMID- 29587806
TI  - A comparison study on the behavior of human endometrial stem cell-derived
      osteoblast cells on PLGA/HA nanocomposite scaffolds fabricated by electrospinning
      and freeze-drying methods.
AB  - BACKGROUND: An engineered tissue structure is an artificial scaffold combined
      with cells and signaling factors. Among various polymers, the polylactide-co
      glycolide/hydroxyapatite (PLGA/HA) has attracted much attention due to their
      optimal properties. The aim of this study was to study the behavior of human
      endometrial stem cell (hEnSC)-derived osteoblast cells cultured on PLGA/HA
      nanocomposite scaffolds. METHODS: hEnSCs were isolated and exposed to osteogenic
      media for 21 days. Differentiated cells were cultured on PLGA/HA synthetic
      scaffolds. The PLGA/HA-based nanocomposite scaffolds were fabricated using either
      electrospinning or freeze-drying methods. Behavior of the cells was evaluated a
      week after seeding hEnSC-derived osteoblast-like cells on these scaffolds.
      Osteogenesis was investigated in terms of alkaline phosphatase activity, gene
      expression, immunocytochemistry (ICC), proliferation, and scanning electron
      microscopy (SEM). Moreover, scaffold properties, such as pore size and morphology
      of the cells, onto the scaffolds were evaluated using SEM. Furthermore,
      biocompatibility of these scaffolds was confirmed by 3-(4,5-dimethylthiazoyl-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The matrix
      mineralization was proved by alizarin red staining, and the osteogenic media
      treated cultures positively expressed osteocalcin and osteopontin markers.
      Moreover, qRT-PCR results confirmed the positive gene expression of osteopontin
      and osteonectin in the differentiated osteoblast-like cells. The results of
      behavior assessment of the cultured cells on electrospinning and freeze-dried
      scaffolds showed that the behavior of the cultured cells on the freeze-dried
      PLGA/HA scaffolds was significantly better than the electrospinning PLGA/HA
      scaffolds. CONCLUSION: It has been shown that the freeze-dried PLGA/HA
      nanocomposite scaffolds can appropriately support the attachment and
      proliferation of the differentiated osteoblast cells and are a suitable candidate
      for bone tissue engineering.

PMID- 29587807
TI  - Acceptance and Commitment Therapy preceded by an experimental Attention Bias
      Modification procedure in recurrent depression: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: This project studies the effect of group-based Acceptance and
      Commitment Therapy (ACT) following Attention Bias Modification (ABM) on residual
      symptoms in recurrent depression. ACT is a cognitive-behavioral intervention
      combining acceptance and mindfulness processes with commitment and behavior
      change processes. ACT enjoys modest empirical support in treating depression and
      has also shown promising results in secondary prevention of depression. The
      experimental cognitive bias modification (ABM) procedure has been shown to reduce
      surrogate markers of depression vulnerability in patients in remission from
      depression. The aim of the current project is to investigate if the effect of
      group-based ACT on reducing residual depressive symptoms can be enhanced by
      preceding it with ABM. Also, assessment of the relationship between conceptually
      relevant therapeutic processes and outcome will be investigated. METHODS/DESIGN:
      An invitation to participate in this project was extended to 120 individuals
      within a larger sample who had just completed a separate randomized, multisite,
      clinical trial (referred to hereafter as Phase 1) in which they received either
      ABM (n = 60) or a control condition without bias modification (n = 60). This
      larger Phase-1 sample consisted of 220 persons with a history of at least two
      episodes of major depression who were currently in remission or not fulfilling
      the criteria of major depression. After its inclusion, Phase-1 participants from
      the Sorlandet site (n = 120) were also recruited for this study in which they
      received an 8-week group-based ACT intervention. Measures will be taken
      immediately after Phase 1, 1 month, 2 months, 6 months, and 1 year after the
      conclusion of Phase 1. DISCUSSION: This study sequentially combines acceptable,
      nondrug interventions from neuropsychology and cognitive-behavioral psychology in
      treating residual symptoms in depression. The results will provide information
      about the effectiveness of treatment and on mechanisms and processes of change
      that may be valuable in understanding and further developing ABM and ACT,
      combined and alone. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier:
      NCT02648165 . Registered on 6 January 2016.

PMID- 29587808
TI  - The ideal time of systemic metronidazole and amoxicillin administration in the
      treatment of severe periodontitis: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: The combination of systemic metronidazole (MTZ) and amoxicillin (AMX)
      with scaling and root planing (SRP) has shown to be an effective periodontal
      treatment. However, some essential issues associated with the use of these
      antibiotics remain unanswered, such as the ideal time of administration during
      the course of periodontal treatment. Although these agents are often prescribed
      after the healing phase of the SRP procedure, there is biological plausibility to
      support its use in conjunction with the mechanical treatment. However, to date,
      no placebo controlled randomized clinical trial (RCT) has directly compared these
      two protocols. Therefore, the aim of this RCT is to compare the clinical,
      microbiological and immunological effects of the adjunctive systemic MTZ + AMX
      administered in different phases of the treatment of severe periodontitis.
      METHODS: Subjects with severe periodontitis (n = 180) are being randomly assigned
      into three groups (n = 60/group): (i) SRP-only (control group), SRP in
      combination with 400 mg MTZ + 500 mg AMX, starting (ii) at the first SRP session
      (active phase group), or (iii) after 3 months of its completion (healing phase
      group). All volunteers are receiving clinical and microbiological evaluation at
      baseline, 3, 6 and 12 months, and immunological assessment at baseline and 12
      months post-therapy. Nine subgingival biofilm samples are being collected per
      subject and analyzed for counts and proportions of 40 bacterial species by
      checkerboard DNA-DNA hybridization, and six gingival crevicular fluid samples are
      being collected and analyzed for the levels of 20 chemokines by multiplex
      immunoassay. The primary outcome variable is the number of volunteers reaching
      the clinical endpoint for treatment (<= 4 sites with probing depth >=5 mm) at 1
      year post-therapy. Differences in clinical, microbiological and immunological
      parameters among groups and over time will be evaluated using analysis of
      variance, analysis of covariance and the Chi-square and Tukey tests.
      Microbiological and immunological analyses will be performed using adjustments
      for multiple comparisons. Statistical significance will be set at 5%. TRIAL
      REGISTRATION: ClinicalTrials.gov , NCT02954393 . Registered on 3 November 2016.

PMID- 29587809
TI  - Assessing the outcomes of everolimus on renal angiomyolipoma associated with
      tuberous sclerosis complex in China: a two years trial.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic
      disorder characterized by the development of numerous benign tumors. Renal
      angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading
      cause of TSC-related death in adult patients. The aim of the study was to
      evaluate the efficacy and safety profiles of everolimus in Chinese patients of
      TSC associated with RAML(TSC-RAML). METHODS: In this 2-years, nonrandomized, open
      label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in
      its longest diameter, were enrolled to assess the efficacy and safety of
      everolimus therapy in Chinese patients. Everolimus was administered for the first
      12 months only. The primary endpoint was a reduction of 50% or more relative in
      RAML volume to the baseline in the absence of new RAML >=1 cm and no RAML-related
      bleeding of grade >= 2. The secondary endpoints included: safety, lung function
      and skin lesions response rate. Serial computed tomography of RAML, magnetic
      resonance imaging of brain lesions and pulmonary-function tests were performed.
      Adverse events were investigated using CTCAE v4.0. All analyses used a
      significance level of 0.05 and were generated in SPSS19.0 software. RESULTS: The
      proportion of patients who achieved >=50% reduction from baseline in the sum of
      volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67%
      at months 6 and 12, respectively. During the period of everolimus therapy, among
      patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s
      (FEV1) increased by 276 +/- 78 ml (P < 0.001), the forced vital capacity (FVC)
      increased by 433 +/- 170 ml (P < 0.001), and the residual volume decreased by 408
      +/- 243 ml (P = 0.009), as compared with baseline values. The angiomyolipoma
      volume and the lung function approached, but did not completely return to, the
      baseline values. The skin lesions response rate was 37.5% after 12 months of
      therapy falling to 21.4% at 12 months after stopping everolimus. The most common
      adverse events were mucositis oral, irregular menstruation, abdominal pain,
      hypertriglyceridemia and headache. The most common grade 3 adverse events were
      irregular menstruation and mucositis oral. In addition, one patient died from
      RAML spontaneous haemorrhage during treatment with everolimus, even with
      reduction in RAML volume of 60.68% at 3 months. A second death was due to
      epithelioid RAML progression, with metastasis to multiple retroperitoneal lymph
      node, who died from severe infection one month after surgery. CONCLUSIONS:
      Angiomyolipomas regressed somewhat during everolimus therapy but tended to
      increase in volume after the therapy was stopped. Everolimus was well tolerated
      and showed promising activity in Chinese patients with TSC-RAML, however, we
      should alert the life-threatening hemorrhage of large RAML in the early period
      and the lymph node metastasis of epithelioid RAML. TRIAL REGISTRATION: ChiCTR-OPC
      14005488 . Registered November 17, 2014.

PMID- 29587810
TI  - Pre-hospital extra-corporeal cardiopulmonary resuscitation.
AB  - Survival from out-of-hospital cardiac arrest (OHCA) has remained low despite
      advances in resuscitation science. Hospital-based extra-corporeal cardiopulmonary
      resuscitation (ECPR) is a novel use of an established technology that provides
      greater blood flow and oxygen delivery during cardiac arrest than closed chest
      compressions. Hospital-based ECPR is currently offered to selected OHCA patients
      in specialized centres. The interval between collapse and restoration of
      circulation is inversely associated with good clinical outcomes after ECPR. Pre
      hospital delivery of ECPR concurrent with conventional resuscitation is one
      approach to shortening this interval and improving outcomes after OHCA. This
      article examines the background and rationale for pre-hospital ECPR; summarises
      the findings of a literature search for published evidence; and considers
      candidate selection, logistics, and complications for this complex intervention.

PMID- 29587812
TI  - Validation of the Neonatal Satisfaction Survey (NSS-8) in six Norwegian neonatal
      intensive care units: a quantitative cross-sectional study.
AB  - BACKGROUND: The experience of having their new-borns admitted to an intensive
      care unit (NICU) can be extremely distressing. Subsequent risk of post-incident
      adjustment difficulties are increased for parents, siblings, and affected
      families. Patient and next of kin satisfaction surveys provide key indicators of
      quality in health care. Methodically constructed and validated survey tools are
      in short supply and parents' experiences of care in Neonatal Intensive Care Units
      is under-researched. This paper reports a validation of the Neonatal Satisfaction
      Survey (NSS-8) in six Norwegian NICUs. METHODS: Parents' survey returns were
      collected using the Neonatal Satisfaction Survey (NSS-13). Data quality and
      psychometric properties were systematically assessed using exploratory factor
      analysis, tests of internal consistency, reliability, construct, convergent and
      discriminant validity. Each set of hospital returns were subjected to an apostasy
      analysis before an overall satisfaction rate was calculated. RESULTS: The survey
      sample of 568 parents represents 45% of total eligible population for the period
      of the study. Missing data accounted for 1,1% of all returns. Attrition analysis
      shows congruence between sample and total population. Exploratory factor analysis
      identified eight factors of concern to parents,"Care and Treatment", "Doctors",
      "Visits", "Information", "Facilities", "Parents' Anxiety", "Discharge" and
      "Sibling Visits". All factors showed satisfactory internal consistency, good
      reliability (Cronbach's alpha ranged from 0.70-0.94). For the whole scale of 51
      items alpha 0.95. Convergent validity using Spearman's rank between the eight
      factors and question measuring overall satisfaction was significant on all
      factors. Discriminant validity was established for all factors. Overall
      satisfaction rates ranged from 86 to 90% while for each of the eight factors
      measures of satisfaction varied between 64 and 86%. CONCLUSION: The NSS-8
      questionnaire is a valid and reliable scale for measuring parents' assessment of
      quality of care in NICU. Statistical analysis confirms the instrument's capacity
      to gauge parents' experiences of NICU. Further research is indicated to validate
      the survey questionnaire in other Nordic countries and beyond.

PMID- 29587813
TI  - Use patterns, use values and management of Afzelia africana Sm. in Burkina Faso:
      implications for species domestication and sustainable conservation.
AB  - BACKGROUND: The lack of literature on the interactions between indigenous people
      and the valuable agroforestry trees hinder the promotion of sustainable
      management of plant resources in West African Sahel. This study aimed at
      assessing local uses and management of Afzelia africana Sm. in Burkina Faso, as a
      prerequisite to address issues of domestication and sustainable conservation.
      METHODS: One thousand forty-four peoples of seven dominant ethnic groups were
      questioned in 11 villages through 221 semi-structured focus group interviews. The
      surveys encompassed several rural communities living around six protected areas
      along the species distribution range. Questions refer mainly to vernacular names
      of A. africana, locals' motivations to conserve the species, the uses, management
      practices and local ecological knowledge on the species. Citation frequency was
      calculated for each response item of each questionnaire section to obtain
      quantitative data. The quantitative data were then submitted to comparison tests
      and multivariate statistics in R program. RESULTS: A. africana is a locally well
      known tree described as a refuge of invisible spirits. Due to this mystery and
      its multipurpose uses, A. africana is conserved within the agroforestry systems.
      The species is widely and mostly used as fodder (87.55%), drugs (75.93%), fetish
      or sanctuary (70.95%), food (41.49%), and raw material for carpentry (36.19%) and
      construction (7.05%). While the uses as fodder, food and construction involved
      one organ, the leaves and wood respectively, the medicinal use was the most
      diversified. All tree organs were traditionally used in 10 medical prescriptions
      to cure about 20 diseases. The species use values differed between ethnic groups
      with lower values within the Dagara and Fulani. The findings reveal a total
      absence of specific management practices such as assisted natural regeneration,
      seeding, or transplantation of A. africana sapling. However, trees were
      permanently pruned and debarked by local people. Harvesting of barks mostly
      contributed to the decline of the species populations. Local people acknowledged
      declining populations of A. africana with lower densities within the
      agroecosystems. They also perceived between individuals, variations in the traits
      of barks, leaves, fruits and seeds. Significant differences were found between
      ethnic groups and gender regarding the species uses. Local knowledge on the
      species distribution differed between ethnic groups. CONCLUSION: This study
      showed the multipurpose uses of A. africana throughout Burkina Faso. The results
      provide relevant social and ecological indicators to all stakeholders and
      constitute a springboard towards the species domestication and the elaboration of
      efficient sustainable conservation plans.

PMID- 29587811
TI  - Angiostrongylus vasorum and Aelurostrongylus abstrusus: Neglected and
      underestimated parasites in South America.
AB  - The gastropod-borne nematodes Angiostrongylus vasorum and Aelurostrongylus
      abstrusus are global causes of cardio/pulmonary diseases in dogs and cats. In the
      last decade, the number of reports on canine and feline lungworms has increased
      in several areas of Europe and North America. The unspecific clinical signs and
      prolonged course of these diseases often renders diagnosis challenging. Both
      infections are considered as emerging and underestimated causes of disease in
      domestic pets. In South America, little information is available on these
      diseases, apart from occasional reports proving the principle presence of A.
      vasorum and A. abstrusus. Thus, the purpose of this review is to summarize
      reports on infections in both domestic and wildlife animals in South America and
      to increase the awareness on gastropod-borne metastrongyloid parasites, which
      also include important zoonotic species, such as A. cantonensis and A.
      costaricensis. This review highlights the usefulness of diagnostic tools, such as
      the Baermann funnel technique, serology and PCR, and proposes to include these
      routinely on cases with clinical suspicion for lungworm infections. Future
      national epidemiological surveys are recommended to be conducted to gain a deeper
      insight into the actual epidemiological situation of gastropod-borne parasitoses
      in South America.

PMID- 29587814
TI  - A comparative analysis of pharmacists' perspectives on codeine use and misuse - a
      three country survey.
AB  - BACKGROUND: The misuse of codeine is of increasing concern in a number of
      countries, particularly as this relates to over -the-counter pain and cough
      relief medication, and is also supplied as a prescription medicine. The study
      aimed to obtain and analyse the opinions and experience of pharmacy staff with
      regard to codeine misuse. METHODS: A cross-sectional web-based survey of pharmacy
      staff's perspectives on this issue was administered through professional or
      regulatory bodies and completed by samples drawn in South Africa (n = 124),
      Ireland (n = 464) and the United Kingdom (n = 129). RESULTS: The majority of
      participants reported combination codeine-containing products as most popular,
      but significantly more pharmacy staff in South Africa reported codeine-containing
      cough syrups as most commonly popular (X2 = 122.7(2), p < 0.001). Codeine use was
      also seen significantly more of a public health problem in South Africa than in
      the other two countries (X2 = 7.6(2), p = 0.02). There was no difference across
      countries in the level of codeine misuse reported by pharmacy staff. Further
      findings indicate that professional training and education is desired, with
      unequivocal findings for the need for greater codeine control (X2 = 12.0(2), p =
      0.002). CONCLUSION: In conclusion, there were some inter-country differences, but
      overall the findings seem to suggest that pharmacists across all three countries
      view codeine misuse as a problem among their customers. Recommendations centre on
      risk management, surveillance and staff training.

PMID- 29587815
TI  - Pleural effusion from intrathoracic migration of a ventriculo-peritoneal shunt
      catheter: pediatric case report and review of the literature.
AB  - BACKGROUND: Pleural effusion is a rare complication of ventriculo-peritoneal (VP)
      cerebrospinal fluid (CSF) shunting and its diagnosis is difficult in patients
      with neurological and consciousness impairment. CASE REPORT: Herein we report the
      case of a child affected by Pfeiffer syndrome and hydrocephalus, shunted at the
      age of 3 months, who developed acute respiratory failure due to a right-sided
      pleural effusion 2 years later. Plain chest radiographs and computed tomography
      (CT) showed the intrathoracic migration of the right VP shunt abdominal tip. Beta
      2 transferrin, a marker for CSF, was found in the pleural fluid and the
      hypothesis of a CSF hydrothorax was confirmed. Effusion was treated with a
      thoracentesis. Seven days after, the right VP shunt was revised; a ventriculo
      atrial (VA) shunt was also placed on the left side to serve as the main CSF shunt
      and to prevent the recurrence of hydrothorax. We review the pediatric cases of
      CSF hydrothorax reported in the literature and discuss the mechanisms underlying
      this complication together with the possible treatments. CONCLUSION: Pleural
      effusion due to VP shunt insertion is a rare and potentially life-threatening
      condition that should be suspected in any patient with a VP shunt and respiratory
      failure. Signs of hydrothorax may moreover represent the only clinical evidence
      of a shunt-related complication in case of neurologically severely compromised
      patients in which neurologic examination cannot help to make a diagnosis.

PMID- 29587816
TI  - Indicators of intensive care unit capacity strain: a systematic review.
AB  - BACKGROUND: Strained intensive care unit (ICU) capacity represents a fundamental
      supply-demand mismatch in ICU resources. Strain is likely to be influenced by a
      range of factors; however, there has been no systematic evaluation of the
      spectrum of measures that may indicate strain on ICU capacity. METHODS: We
      performed a systematic review to identify indicators of strained capacity. A
      comprehensive peer-reviewed search of MEDLINE, EMBASE, CINAHL, Cochrane Library,
      and Web of Science Core Collection was performed along with selected grey
      literature sources. We included studies published in English after 1990. We
      included studies that: (1) focused on ICU settings; (2) included description of a
      quality or performance measure; and (3) described strained capacity. Retrieved
      studies were screened, selected and extracted in duplicate. Quality was assessed
      using the Newcastle-Ottawa Quality Assessment Scale (NOS). Analysis was
      descriptive. RESULTS: Of 5297 studies identified in our search; 51 fulfilled
      eligibility. Most were cohort studies (n = 39; 76.5%), five (9.8%) were case
      control, three (5.8%) were cross-sectional, two (3.9%) were modeling studies, one
      (2%) was a correlational study, and one (2%) was a quality improvement project.
      Most observational studies were high quality. Sixteen measures designed to
      indicate strain were identified 110 times, and classified as structure (n = 4,
      25%), process (n = 7, 44%) and outcome (n = 5, 31%) indicators, respectively. The
      most commonly identified indicators of strain were ICU acuity (n = 21; 19.1%
      [process]), ICU readmission (n = 18; 16.4% [outcome]), after-hours discharge (n =
      15; 13.6% [process]) and ICU census (n = 13; 11.8% [structure]). There was
      substantial heterogeneity in the operational definitions used to define strain
      indicators across studies. CONCLUSIONS: We identified and characterized 16
      indicators of strained ICU capacity across the spectrum of healthcare quality
      domains. Future work should aim to evaluate their implementation into practice
      and assess their value for evaluating strategies to mitigate strain. SYSTEMATIC
      REVIEW REGISTRATION: This systematic review was registered at PROSPERO (March 27,
      2015; CRD42015017931 ).

PMID- 29587817
TI  - The effect of chlorhexidine on dental calculus formation: an in vitro study.
AB  - BACKGROUND: Chlorhexidine gluconate (CHG) has been proven to be effective in
      preventing and controlling biofilm formation. At the same time, an increase in
      calculus formation is known as one of considerable side effects. The purpose of
      this study was to investigate whether mineral deposition preceding a calculus
      formation would occur at an early stage after the use of CHG using an in vitro
      saliva-related biofilm model. METHODS: Biofilms were developed on the MBECTM
      device in brain heart infusion (BHI) broth containing 0.5% sucrose at 37  degrees
      C for 3 days under anaerobic conditions. Biofilms were periodically exposed to 1
      min applications of 0.12% CHG every 12 h and incubated for up to 2 days in BHI
      containing a calcifying solution. Calcium and phosphate in the biofilm were
      measured using atomic absorption spectrophotometry and a phosphate assay kit,
      respectively. Morphological structure was observed using a scanning electron
      microscope (SEM), and chemical composition was analyzed with an electron probe
      microanalyzer (EPMA). RESULTS: The concentrations of Ca and Pi following a single
      exposure to CHG increased significantly compared with the control. Repeatedly
      exposing biofilms to CHG dose-dependently increased Ca deposition, and the amount
      of Ca was five times as much as that of the control. Pi levels in CHG-treated
      biofilms were significantly higher than those from the control group (p < 0.05);
      however, the influence of the number of exposures was limited. Analyses using an
      SEM and EPMA showed many clusters containing calcium and phosphate complexes in
      CHG-treated biofilms. Upon composition analysis of the clusters, calcium was
      detected at a greater concentration than phosphate. CONCLUSIONS: Findings
      suggested that CHG may promote mineral uptake into the biofilm soon after its
      use. It is necessary to disrupt the biofilm prior to the start of a CHG mouthwash
      in order to reduce the side effects associated with this procedure. The
      management of patients is also important.

PMID- 29587818
TI  - 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA
      from patients with non-small cell lung cancer.
AB  - BACKGROUND: Detecting an ALK fusion gene in patients with non-small cell lung
      cancer (NSCLC) could provide evidence to guide individualized therapy. METHODS:
      The 5'/3' imbalance strategy for quantitative reverse transcription-PCR (RT-qPCR)
      was developed to detect ALK fusion genes in circulating tumor RNA (ctRNA) of
      NSCLC patients. RESULTS: This method was validated in patients with the ALK
      fusion gene confirmed by next generation sequencing (NGS). The amount of the ALK
      fusion gene detected by the new method ranged from 33.2 to 987.4, (mean 315.2),
      in the patients confirmed to have the ALK fusion gene (+). This is much higher
      than the amount of fusion gene detected in the patients who are negative for the
      ALK fusion gene (-). The amount detected in the ALK fusion gene (-) samples
      ranged from 0.36 to 13.04, (mean 4.58). In 188 NSCLC patients, the specificity
      and sensitivity of the method was compared to that of the FISH method. About
      10.64% of the patients showed higher ALK fusion gene expression, and were
      classified as ALK fusion gene (+). This is identical to the percentage of
      patients detected by the FISH method to be ALK fusion gene (+). The cutoff value
      for diagnosis of ALK fusion (+) is 32.9 as determined by this method.
      CONCLUSIONS: A new RT-PCR method using a 5'/3' imbalance strategy was developed,
      with high specificity and sensitivity, for detection of the ALK fusion gene in
      ctRNA of NSCLC patients. This method can rapidly detect ALK fusion genes in
      patients, which will be helpful for guiding targeted therapy, particularly the
      individualized usage of TKIs in these patients.

PMID- 29587819
TI  - Diverse laboratory colonies of Aedes aegypti harbor the same adult midgut
      bacterial microbiome.
AB  - BACKGROUND: Host-associated microbes, collectively known as the microbiota, play
      an important role in the biology of multicellular organisms. In mosquito vectors
      of human pathogens, the gut bacterial microbiota influences vectorial capacity
      and has become the subject of intense study. In laboratory studies of vector
      biology, genetic effects are often inferred from differences between
      geographically and genetically diverse colonies of mosquitoes that are reared in
      the same insectary. It is unclear, however, to what extent genetic effects can be
      confounded by uncontrolled differences in the microbiota composition among
      mosquito colonies. To address this question, we used 16S metagenomics to compare
      the midgut bacterial microbiome of six laboratory colonies of Aedes aegypti
      recently derived from wild populations representing the geographical range and
      genetic diversity of the species. RESULTS: We found that the diversity,
      abundance, and community structure of the midgut bacterial microbiome was
      remarkably similar among the six different colonies of Ae. aegypti, regardless of
      their geographical origin. We also confirmed the relatively low complexity of
      bacterial communities inhabiting the mosquito midgut. CONCLUSIONS: Our finding
      that geographically diverse colonies of Ae. aegypti reared in the same insectary
      harbor a similar gut bacterial microbiome supports the conclusion that the gut
      microbiota of adult mosquitoes is environmentally determined regardless of the
      host genotype. Thus, uncontrolled differences in microbiota composition are
      unlikely to represent a significant confounding factor in genetic studies of
      vector biology.

PMID- 29587820
TI  - The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with
      PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells.

PMID- 29587821
TI  - Study on the species composition and ecology of anophelines in Addis Zemen, South
      Gondar, Ethiopia.
AB  - BACKGROUND: Malaria is a public health problem in Ethiopia and its transmission
      is generally unstable and seasonal. For the selection of the most appropriate
      vector control measures, knowledge on the ecology of the vector is necessary at a
      local level. Therefore, the objectives of this study were to document the species
      composition, breeding habitat characteristics and occurrence of anopheline larva
      in Sheni stream and the vectorial role of the prevailing Anopheles in relation to
      malaria transmission in Addis Zemen, Ethiopia. METHODS: Immature anophelines were
      sampled from breeding habitats and characteristics, such as water temperature,
      turbidity, water current, water pH and other variables, of the habitats were
      measured from October 2011 to February 2012. Adult anophelines were sampled
      inside human dwellings using space spray and Center for Disease Control light
      traps. Artificial pit shelters and clay pots were also used for outdoor adult
      collections. Anophelines collected were identified using morphological key. The
      enzyme-linked immunosorbent assay was applied to detect circumsporozoite proteins
      of Plasmodium and source of blood meals. RESULTS: A total of 6258 Anopheles
      larvae were collected and identified morphologically. Five anopheline species
      were found: An. gambiae (s.l.), An. cinereus, An. demeilloni, An. christi and An.
      pretoriensis. Anopheles gambiae (s.l.) existed in most of the habitats
      investigated. Only the former three species were captured in the adult
      collections. Sun-lit Sheni stream, rain pools, hoof prints, drainage and
      irrigation canals were found to be habitats of larvae. Anopheles gambiae (s.l.)
      larvae were most abundantly sampled from sand mining and natural sand pools of
      Sheni stream. Multiple regression analysis showed that clear, permanent and
      temporary habitats devoid of mats of algae were the best predictors of An.
      gambiae (s.l.) larval abundance. It is also the responsible malaria vector in the
      study area and exhibits anthropophilic and endophagic behaviour. CONCLUSIONS: The
      malaria vector An. gambiae (s.l.) was found in Addis Zemen throughout the study
      period from both adult and larval collections. Sheni stream is the main larval
      habitat responsible for the occurrence of anopheline larvae during the dry season
      of the study area when other breeding sites perish.

PMID- 29587822
TI  - Degenerate codon mixing for PCR-based manipulation of highly repetitive
      sequences.
AB  - OBJECTIVE: Repeat expansion of polyglutamine tracks leads to a group of inherited
      human neurodegenerative disorders. Studying such repetitive sequences is required
      to gain insight into the pathophysiology of these diseases. PCR-based
      manipulation of repetitive sequences, however, is challenging due to the absence
      of unique primer binding sites or the generation of non-specific products.
      RESULTS: We have utilised the degeneracy of the genetic code to generate a
      polyglutamine sequence with low repeat similarity. This strategy allowed us to
      use conventional PCR to generate multiple constructs with approximately defined
      numbers of glutamine repeats. We then used these constructs to measure the in
      vivo variation in autophagic degradation activity related to the different
      numbers of glutamine repeats, providing an example of their applicability to
      study repeat expansion diseases. Our simple and easily generalised method of
      generating low repetition DNA sequences coding for uniform stretches of amino
      acid residues provides a strategy for generating particular lengths of
      polyglutamine tracts using standard PCR and cloning protocols.

PMID- 29587823
TI  - Multiple functions of m6A RNA methylation in cancer.
AB  - First identified in 1974, m6A RNA methylation, which serves as a predominant
      internal modification of RNA in higher eukaryotes, has gained prodigious interest
      in recent years. Modifications of m6A are dynamic and reversible in mammalian
      cells, which have been proposed as another layer of epigenetic regulation similar
      to DNA and histone modifications. m6A RNA methylation is involved in all stages
      in the life cycle of RNA, ranging from RNA processing, through nuclear export,
      translation modulation to RNA degradation, which suggests its potential of
      influencing a plurality of aspects of RNA metabolism. All of the recent studies
      have pointed to a complicated regulation network of m6A modification in different
      tissues, cell lines, and space-time models. m6A methylation has been found to
      have an impact on tumor initiation and progression through various mechanisms.
      Furthermore, m6A RNA methylation has provided new opportunities for early stage
      diagnosis and treatment of cancers.Herein, we review the chemical basis of m6A
      RNA methylation, its multiple functions and potential significance in cancer.

PMID- 29587824
TI  - Distinctive epigenomes characterize glioma stem cells and their response to
      differentiation cues.
AB  - BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of stem-like cells that
      contribute to glioblastoma (GBM) aggressiveness, recurrence, and resistance to
      radiation and chemotherapy. Therapeutically targeting the GSC population may
      improve patient survival, but unique vulnerabilities need to be identified.
      RESULTS: We isolate GSCs from well-characterized GBM patient-derived xenografts
      (PDX), characterize their stemness properties using immunofluorescence staining,
      profile their epigenome including 5mC, 5hmC, 5fC/5caC, and two enhancer marks,
      and define their transcriptome. Fetal brain-derived neural stem/progenitor cells
      are used as a comparison to define potential unique and common molecular features
      between these different brain-derived cells with stem properties. Our integrative
      study reveals that abnormal expression of ten-eleven-translocation (TET) family
      members correlates with global levels of 5mC and 5fC/5caC and may be responsible
      for the distinct levels of these marks between glioma and neural stem cells.
      Heterogenous transcriptome and epigenome signatures among GSCs converge on
      several genes and pathways, including DNA damage response and cell proliferation,
      which are highly correlated with TET expression. Distinct enhancer landscapes are
      also strongly associated with differential gene regulation between glioma and
      neural stem cells; they exhibit unique co-localization patterns with DNA
      epigenetic mark switching events. Upon differentiation, glioma and neural stem
      cells exhibit distinct responses with regard to TET expression and DNA mark
      changes in the genome and GSCs fail to properly remodel their epigenome.
      CONCLUSIONS: Our integrative epigenomic and transcriptomic characterization
      reveals fundamentally distinct yet potentially targetable biologic features of
      GSCs that result from their distinct epigenomic landscapes.

PMID- 29587825
TI  - Inflammatory interferon activates HIF-1alpha-mediated epithelial-to-mesenchymal
      transition via PI3K/AKT/mTOR pathway.
AB  - BACKGROUND: Tumor microenvironments (TMEs) activate various axes/pathways,
      predominantly inflammatory and hypoxic responses, impact tumorigenesis,
      metastasis and therapeutic resistance significantly. Although molecular pathways
      of individual TME are extensively studied, evidence showing interaction and
      crosstalk between hypoxia and inflammation remain unclear. Thus, we examined
      whether interferon (IFN) could modulate both inflammatory and hypoxic responses
      under normoxia and its relation with cancer development. METHODS: IFN was used to
      induce inflammation response and HIF-1alpha expression in various cancer cell
      lines. Corresponding signaling pathways were then analyzed by a combination of
      pharmacological inhibitors, immunoblotting, GST-Raf pull-down assays, dominant
      negative and short-hairpin RNA-mediated knockdown approaches. Specifically, roles
      of functional HIF-1alpha in the IFN-induced epithelial-mesenchymal transition
      (EMT) and other tumorigenic propensities were examined by knockdown,
      pharmacological inhibition, luciferase reporter, clonogenic, anchorage
      independent growth, wound-healing, vasculogenic mimicry, invasion and sphere
      formation assays as well as cellular morphology observation. RESULTS: We showed
      for the first time that IFN induced functional HIF-1alpha expression in a time-
      and dose- dependent manner in various cancer cell lines under both hypoxic and
      normoxic conditions, and then leading to an activated HIF-1alpha pathway in an
      IFN-mediated pro-inflammatory TME. IFN regulates anti-apoptosis activity,
      cellular metastasis, EMT and vasculogenic mimicry by a novel mechanism through
      mainly the activation of PI3K/AKT/mTOR axis. Subsequently, pharmacological and
      genetic modulations of HIF-1alpha, JAK, PI3K/AKT/mTOR or p38 pathways efficiently
      abrogate above IFN-induced tumorigenic propensities. Moreover, HIF-1alpha is
      required for the IFN-induced invasiveness, tumorigenesis and vasculogenic
      mimicry. Further supports for the HIF-1alpha-dependent tumorigenesis were
      obtained from results of xenograft mouse model and sphere-formation assay.
      CONCLUSIONS: Our mechanistic study showed an induction of HIF-1alpha and EMT
      ability in an IFN-mediated inflammatory TME and thus demonstrating a novel
      interaction between inflammatory and hypoxic TMEs. Moreover, targeting HIF-1alpha
      may be a potential target for inhibiting tumor tumorigenesis and EMT by
      decreasing cancer cells wound healing and anchorage-independent colony growth.
      Our results also lead to rationale guidance for developing new therapeutic
      strategies to prevent relapse via targeting TME-providing IFN signaling and HIF
      1alpha programming.

PMID- 29587826
TI  - Life course factors associated with metabolically healthy obesity: a protocol for
      the systematic review of longitudinal studies.
AB  - BACKGROUND: There is heterogeneity among obese individuals, as some appear to
      have healthier metabolic profiles and decreased health risks. These individuals
      are defined as metabolically healthy obese (MHO), whilst those with unhealthy
      metabolic profiles are defined as metabolically unhealthy obese (MUO). To date,
      most research on MHO has been cross-sectional or focused on disease prognosis.
      However, longitudinal studies are required to provide greater insight into the
      life course factors that contribute to the development of MHO. This study aims to
      systematically review longitudinal studies investigating the association between
      life course exposures and future MHO status. METHODS: Electronic databases
      (MEDLINE, SCOPUS, and Web of Science) will be searched using a trialled search
      strategy. Studies will be included following a double-screening process according
      to inclusion criteria to assess eligibility. Studies eligible for inclusion will
      include those that have a longitudinal observational design where a life course
      exposure occurred or was measured at least 1 year before the outcome, investigate
      a human study population, are published in English after 1956, and investigate
      the association between >= 1 life course exposure and >= 1 outcome that reflects
      a measure of cardiometabolic resilience to obesity. Accepted life course
      exposures will include body size, body composition, pubertal development,
      smoking, diet, physical activity, sedentary behaviour, and psychosocial stress.
      The primary measure of cardiometabolic resilience to obesity will be MHO as an
      outcome (at follow-up). Studies investigating the development of cardiometabolic
      risk factors in an obese group without specifying MHO will also be accepted, such
      as the development of the metabolic syndrome (MetS) in an obese group. Key
      results of included studies will be tabulated, and a narrative synthesis will be
      conducted. DISCUSSION: This will be the first systematic review to summarise the
      literature on the life course correlates of MHO. Importantly, it may highlight
      which modifiable lifestyle factors could be targeted to delay the onset of
      cardiometabolic complications among the obese. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017057992.

PMID- 29587827
TI  - Use of a meta-analysis to assess the preventive effect of dexmedetomidine on
      cardiac surgery-associated acute kidney injury.

PMID- 29587828
TI  - The need to revisit the definition of mesenchymal and adult stem cells based on
      their functional attributes.
AB  - A debate is ongoing about the 'stem cell' status of mesenchymal stem cells
      (MSCs). This can easily be resolved based on the definition of a stem cell.
      'True' stem cells are expected to undergo asymmetric cell divisions (ACD) whereby
      they divide to self-renew and give rise to a slightly bigger, differentiated
      cell. However, MSCs like any other adult tissue-specific stem cells, including
      hematopoietic (HSCs), spermatogonial (SSCs) and ovarian (OSCs) stem cells, do not
      undergo ACD; rather they undergo rapid symmetrical cell divisions. The true stem
      cells in adult tissues are possibly the pluripotent stem cells termed very small
      embryonic-like stem cells (VSELs), which were recently shown to undergo ACD to
      give rise to tissue-specific stem cells 'progenitors' (currently termed 'adult
      stem cells') that in turn undergo rapid symmetric cell divisions and clonal
      expansion (sphere formation with incomplete cytokinesis) followed by
      differentiation into tissue-specific cell types. MSCs can be cultured from any
      tissue source and are an excellent source of growth factors/cytokines and thus
      could provide a niche for proper functioning of the stem/progenitor cells.

PMID- 29587829
TI  - How do we define and measure sarcopenia? Protocol for a systematic review.
AB  - BACKGROUND: The loss of muscle mass is a natural aging consequence. A reduction
      of muscle mass that surpasses the physiological rate is considered the key factor
      responsible for the development of a geriatric syndrome called sarcopenia.
      However, a new understanding of the importance of muscle quality over quantity is
      rising; as a result, different definitions for sarcopenia has been used. Due to
      the negative impact on elder's health and quality of life, the number of research
      investigating the causes, prevalence, and management of sarcopenia is increasing,
      although a consensus on sarcopenia definition is still missing. This systematic
      review will assess observational studies reporting the presence of sarcopenia
      aiming to verify how sarcopenia is defined, the diagnosis criteria, and the tools
      used for assessment. In addition, we will investigate the influence of the
      definition and diagnostic tools on the prevalence rate. METHODS: Keywords related
      to the condition, population, and type of study will be combined to build a
      search strategy for each of the following databases MEDLINE, EMBASE, CINAHL
      (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and
      Google Scholar. Two independent reviewers will analyze the retrieved papers for
      eligibility and the methodological quality of eligible studies. The definition of
      sarcopenia and diagnostic tools used in each study and the prevalence estimates
      will be extracted. Descriptive statistics will be used to report the definitions
      of sarcopenia, diagnostic tools, and whether these influence or not, the
      prevalence rates. DISCUSSION: Sarcopenia is receiving greater attention in
      geriatrics research in recent years. Therefore, it is important to investigate
      how this condition is defined in the literature and whether these definitions can
      interfere with the reported estimates devoting more efforts on the topic. The
      results of this study can help to determine the most used definitions of
      sarcopenia reported in the literature, its strengths and limitations, and open a
      discussion about a need for a more valid, easy, and suitable one. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42015020832.

PMID- 29587830
TI  - Seasonal and algal diet-driven patterns of the digestive microbiota of the
      European abalone Haliotis tuberculata, a generalist marine herbivore.
AB  - BACKGROUND: Holobionts have a digestive microbiota with catabolic abilities
      allowing the degradation of complex dietary compounds for the host. In
      terrestrial herbivores, the digestive microbiota is known to degrade complex
      polysaccharides from land plants while in marine herbivores, the digestive
      microbiota is poorly characterized. Most of the latter are generalists and
      consume red, green, and brown macroalgae, three distinct lineages characterized
      by a specific composition in complex polysaccharides, which represent half of
      their biomass. Subsequently, each macroalga features a specific epiphytic
      microbiota, and the digestive microbiota of marine herbivores is expected to vary
      with a monospecific algal diet. We investigated the effect of four monospecific
      diets (Palmaria palmata, Ulva lactuca, Saccharina latissima, Laminaria digitata)
      on the composition and specificity of the digestive microbiota of a generalist
      marine herbivore, the abalone, farmed in a temperate coastal area over a year.
      The microbiota from the abalone digestive gland was sampled every 2 months and
      explored using metabarcoding. RESULTS: Diversity and multivariate analyses showed
      that patterns of the microbiota were significantly linked to seasonal variations
      of contextual parameters but not directly to a specific algal diet. Three core
      genera: Psychrilyobacter, Mycoplasma, and Vibrio constantly dominated the
      microbiota in the abalone digestive gland. Additionally, a less abundant and diet
      specific core microbiota featured genera representing aerobic primary degraders
      of algal polysaccharides. CONCLUSIONS: This study highlights the establishment of
      a persistent core microbiota in the digestive gland of the abalone since its
      juvenile state and the presence of a less abundant and diet-specific core
      community. While composed of different microbial taxa compared to terrestrial
      herbivores, the digestive gland constitutes a particular niche in the abalone
      holobiont, where bacteria (i) may cooperate to degrade algal polysaccharides to
      products assimilable by the host or (ii) may have acquired these functions
      through gene transfer from the aerobic algal microbiota.

PMID- 29587831
TI  - Childhood fish oil supplementation modifies associations between traffic related
      air pollution and allergic sensitisation.
AB  - BACKGROUND: Studies of potential adverse effects of traffic related air pollution
      (TRAP) on allergic disease have had mixed findings. Nutritional studies to
      examine whether fish oil supplementation may protect against development of
      allergic disease through their anti-inflammatory actions have also had mixed
      findings. Extremely few studies to date have considered whether air pollution and
      dietary factors such as fish oil intake may interact, which was the rationale for
      this study. METHODS: We conducted a secondary analysis of the Childhood Asthma
      Prevention Study (CAPS) birth cohort, where children were randomised to fish oil
      supplementation or placebo from early life to age 5 years. We examined
      interactions between supplementation and TRAP (using weighted road density at
      place of residence as our measure of traffic related air pollution exposure) with
      allergic disease and lung function outcomes at age 5 and 8 years. RESULTS:
      Outcome information was available on approximately 400 children (~ 70% of the
      original birth cohort). Statistically significant interactions between fish oil
      supplementation and TRAP were seen for house dust mite (HDM), inhalant and all
      allergen skin prick tests (SPTs) and for HDM-specific interleukin-5 response at
      age 5. Adjusting for relevant confounders, relative risks (RRs) for positive HDM
      SPT were RR 1.74 (95% CI 1.22-2.48) per 100 m local road or 33.3 m of motorway
      within 50 m of the home for those randomised to the control group and 1.03 (0.76
      1.41) for those randomised to receive the fish oil supplement. The risk
      differential was highest in an analysis restricted to those who did not change
      address between ages 5 and 8 years. In this sub-group, supplementation also
      protected against the effect of traffic exposure on pre-bronchodilator FEV1/FVC
      ratio. CONCLUSIONS: Results suggest that fish oil supplementation may protect
      against pro-allergic sensitisation effects of TRAP exposure. Strengths of this
      analysis are that supplementation was randomised and independent of TRAP
      exposure, however, findings need to be confirmed in a larger experimental study
      with the interaction investigated as a primary hypothesis, potentially also
      exploring epigenetic mechanisms. More generally, studies of adverse health
      effects of air pollution may benefit from considering potential effect
      modification by diet and other factors. TRIAL REGISTRATION: Australia New Zealand
      Clinical Trial Registry. www.anzctr.org.au Registration: ACTRN12605000042640 ,
      Date: 26th July 2005. Retrospectively registered, trial commenced prior to
      registry availability.

PMID- 29587832
TI  - Community analysis of the abundance and diversity of biting midge species
      (Diptera: Ceratopogonidae) in three European countries at different latitudes.
AB  - BACKGROUND: The outbreaks of bluetongue and Schmallenberg disease in Europe have
      increased efforts to understand the ecology of Culicoides biting midges and their
      role in pathogen transmission. However, most studies have focused on a specific
      habitat, region, or country. To facilitate wider comparisons, and to obtain a
      better understanding of the spread of disease through Europe, the present study
      focused on monitoring biting midge species diversity in three different habitat
      types and three countries across Europe. METHODS: Biting midges were trapped
      using Onderstepoort Veterinary Institute light traps at a total of 27 locations
      in Sweden, the Netherlands and Italy, comprising farm, peri-urban and wetland
      habitats. From July 2014 to June 2015 all locations were sampled monthly, except
      for during the winter months. Trapped midges were counted and identified
      morphologically. Indices on species richness, evenness and diversity were
      calculated. Community compositions were analysed using non-metric
      multidimensional scaling (NMDS) techniques. RESULTS: A total of 50,085 female
      midges were trapped during 442 collection nights. More than 88% of these belonged
      to the Obsoletus group. The highest midge diversity was found in Sweden, while
      species richness was highest in the Netherlands, and most specimens were trapped
      in Italy. For habitats within countries, diversity of the trapped midges was
      lowest for farms in all countries. Differences in biting midge species
      communities were more distinct across the three countries than the three habitat
      types. CONCLUSIONS: A core midge community could be identified, in which the
      Obsoletus group was the most abundant. Variations in vector communities across
      countries imply different patterns of disease spread throughout Europe. How
      specific species and their associated communities affect disease risk is still
      unclear. Our results emphasize the importance of midge diversity data at
      community level, how this differs across large geographic range within Europe,
      and its implications on assessing risks of midge-borne disease outbreaks.

PMID- 29587834
TI  - A standard photomap of ovarian nurse cell chromosomes and inversion polymorphism
      in Anopheles beklemishevi.
AB  - BACKGROUND: Anopheles beklemishevi is a member of the Maculipennis group of
      malaria mosquitoes that has the most northern distribution among other members of
      the group. Although a cytogenetic map for the larval salivary gland chromosomes
      of this species has been developed, a high-quality standard cytogenetic photomap
      that enables genomics and population genetics studies of this mosquito at the
      adult stage is still lacking. METHODS: In this study, a cytogenetic map for the
      polytene chromosomes of An. beklemishevi from ovarian nurse cells was developed
      using high-resolution digital imaging from field collected mosquitoes. PCR
      amplified DNA probes for fluorescence in situ hybridization (FISH) were designed
      based on the genome of An. atroparvus. The DNA probe obtained by microdissection
      procedures from the breakpoint region was labelled in a DOP-PCR reaction.
      Population analysis was performed on 371 specimens collected in 18 locations.
      RESULTS: We report the development of a high-quality standard photomap for the
      polytene chromosomes from ovarian nurse cells of An. beklemishevi. To confirm the
      suitability of the map for physical mapping, several PCR-amplified probes were
      mapped to the chromosomes of An. beklemishevi using FISH. In addition, we
      identified and mapped DNA probes to flanking regions of the breakpoints of two
      inversions on chromosome X of this species. Inversion polymorphism was determined
      in 13 geographically distant populations of An. beklemishevi. Four polymorphic
      inversions were detected. The positions of common chromosomal inversions were
      indicated on the map. CONCLUSIONS: The study constructed a standard photomap for
      ovarian nurse cell chromosomes of An. beklemishevi and tested its suitability for
      physical genome mapping and population studies. Cytogenetic analysis determined
      inversion polymorphism in natural populations of An. beklemishevi related to this
      species' adaptation.

PMID- 29587833
TI  - Use of Hybrid Assistive Limb (HAL(r)) for a postoperative patient with cerebral
      palsy: a case report.
AB  - BACKGROUND: The Hybrid Assistive Limb (HAL(r)) is an exoskeleton wearable robot
      suit that assists in voluntary control of knee and hip joint motion. There have
      been several studies on HAL intervention effects in stroke, spinal cord injury,
      and cerebral palsy. However, no study has investigated HAL intervention for
      patients with cerebral palsy after surgery. CASE PRESENTATION: We report a case
      of using HAL in a postoperative patient with cerebral palsy. A 15-year-old boy
      was diagnosed with spastic diplegia cerebral palsy Gross Motor Function
      Classification System level IV, with knee flection contracture, equinus foot, and
      paralysis of the right upper extremity with adduction contracture. He underwent
      tendon lengthening of the bilateral hamstrings and Achilles tendons. Although the
      flexion contractures of the bilateral knees and equinus foot improved, muscle
      strength decreased after the soft tissue surgery. HAL intervention was performed
      twice during postoperative months 10 and 11. Walking speed, stride, and cadence
      were increased after HAL intervention. Post HAL intervention, extension angles of
      the knee in stance phase and hip in the pre-swing phase were improved. In the
      gait cycle, the proportion of terminal stance in the stance and swing phase was
      increased. CONCLUSIONS: Hybrid Assistive Limb intervention for postoperative
      patients with cerebral palsy whose muscle strength decreases can enhance
      improvement in walking ability. Further studies are needed to examine the safety
      and potential application of HAL in this setting.

PMID- 29587835
TI  - Is adjuvant chemotherapy beneficial for patients with FIGO stage IC adult
      granulosa cell tumor of the ovary?
AB  - BACKGROUND: To evaluate the association between adjuvant chemotherapy and
      clinical outcomes in patients with stage IC adult granulosa cell tumor (AGCT).
      METHODS: We performed a retrospective study of patients with stage IC AGCT
      diagnosed at our hospital from January 1985 to September 2015. We analyzed
      descriptive statistics, and performed univariate and multivariate and Kaplan
      Meier survival analyses. RESULTS: Sixty stage IC AGCT patients were identified,
      including 28 in the no adjuvant chemotherapy group (NACG) and 32 in the adjuvant
      chemotherapy group (ACG). The median follow-up time was 88 months (range: 9-334
      months). Sixteen patients developed recurrences, including nine in the NACG and
      seven in the ACG groups. Univariate analysis identified incomplete surgical
      staging and initial treatment place as associated with disease-free survival
      (DFS) (P = 0.003 and 0.038, respectively). Incomplete surgical staging remained a
      risk factor for recurrence in multivariate analysis (hazard ratio (HR) = 3.883,
      95% confidence interval (CI): 1.123-13.430, P = 0.032). The 5-year DFS rates in
      the NACG and ACG groups were 76.3% and 87.5% respectively (P = 0.197). Adjuvant
      chemotherapy was thus not associated with improved DFS. Furthermore, the number
      of chemotherapy cycles was not associated with recurrence rate (<=3 cycles vs. >
      3 cycles, HR = 0.613, 95% CI: 0.112-3.351, P = 0.572). CONCLUSION: Administration
      of adjuvant chemotherapy does not improve DFS in patients with stage IC AGCT.
      Further studies with larger samples involving multi-institutional collaboration
      are needed to validate new treatment regimens for this disease.

PMID- 29587836
TI  - Atrophy of primary lymphoid organs induced by Marek's disease virus during early
      infection is associated with increased apoptosis, inhibition of cell
      proliferation and a severe B-lymphopenia.
AB  - Marek's disease is a multi-faceted highly contagious disease affecting chickens
      caused by the Marek's disease alphaherpesvirus (MDV). MDV early infection induces
      a transient immunosuppression, which is associated with thymus and bursa of
      Fabricius atrophy. Little is known about the cellular processes involved in
      primary lymphoid organ atrophy. Here, by in situ TUNEL assay, we demonstrate that
      MDV infection results in a high level of apoptosis in the thymus and bursa of
      Fabricius, which is concomitant to the MDV lytic cycle. Interestingly, we
      observed that in the thymus most of the MDV infected cells at 6 days post
      infection (dpi) were apoptotic, whereas in the bursa of Fabricius most of the
      apoptotic cells were uninfected suggesting that MDV triggers apoptosis by two
      different modes in these two primary lymphoid organs. In addition, a high
      decrease of cell proliferation was observed from 6 to 14 dpi in the bursa of
      Fabricius follicles, and not in the thymus. Finally, with an adapted absolute
      blood lymphocyte count, we demonstrate a major B-lymphopenia during the two 1st
      weeks of infection, and propose this method as a potent non-invasive tool to
      diagnose MDV bursa of Fabricius infection and atrophy. Our results demonstrate
      that the thymus and bursa of Fabricius atrophies are related to different cell
      mechanisms, with different temporalities, that affect infected and uninfected
      cells.

PMID- 29587838
TI  - Psychometric properties of the Audit of Diabetes-Dependent Quality of Life
      (ADDQoL) in a population-based sample of Polish adults with type 1 and 2
      diabetes.
AB  - BACKGROUND: The aim of the present paper was the assessment of the psychometric
      properties of the Polish language version of the Audit of Diabetes-Dependent
      Quality of Life (ADDQoL) questionnaire applied in Poland among patients with type
      1 (T1DM) or type 2 diabetes (T2DM). METHODS: The studies were carried out among
      330 patients with diabetes including 115 with T1DM and 215 with T2DM. In all the
      patients the level of the quality of life was investigated using the Polish
      language version of the ADDQoL and the psychometric properties were determined
      taking into consideration internal consistency, the factor loading and intraclass
      correlations. RESULTS: It was demonstrated that the values of internal
      consistency determining the reliability of the Polish language version of the
      ADDQoL for the overall Cronbach's alfa coefficient were 0.92 in the studied
      patients with T1DM and 0.93 in the studied patients with T2DM and the values of
      the loading factor were respectively 0.39-0.79 and 0.35-0.81. In the study of the
      correlation between the components of the ADDQoL the correlation coefficients
      proved to be highly statistically significant: in patients with T1DM r = 0.46
      0.74 and in patients with T2DM - r = 0.42-0.80. CONCLUSION: The Polish language
      version of the ADDQoL is a reliable tool useful for the assessment of the level
      of the quality of life of adult patients with T1DM or T2DM in Poland and is
      recommended to be used among Polish-speaking patients with diabetes.

PMID- 29587837
TI  - Checks and balances? DNA replication and the cell cycle in Plasmodium.
AB  - It is over 100 years since the life-cycle of the malaria parasite Plasmodium was
      discovered, yet its intricacies remain incompletely understood - a knowledge gap
      that may prove crucial for our efforts to control the disease. Phenotypic screens
      have partially filled the void in the antimalarial drug market, but as compound
      libraries eventually become exhausted, new medicines will only come from directed
      drug development based on a better understanding of fundamental parasite biology.
      This review focusses on the unusual cell cycles of Plasmodium, which may present
      a rich source of novel drug targets as well as a topic of fundamental biological
      interest. Plasmodium does not grow by conventional binary fission, but rather by
      several syncytial modes of replication including schizogony and sporogony. Here,
      we collate what is known about the various cell cycle events and their regulators
      throughout the Plasmodium life-cycle, highlighting the differences between
      Plasmodium, model organisms and other apicomplexan parasites and identifying
      areas where further study is required. The possibility of DNA replication and the
      cell cycle as a drug target is also explored. Finally the use of existing tools,
      emerging technologies, their limitations and future directions to elucidate the
      peculiarities of the Plasmodium cell cycle are discussed.

PMID- 29587839
TI  - Species identification approach for both raw materials and end products of herbal
      supplements from Tinospora species.
AB  - BACKGROUND: Nowadays herbal products used in traditional medicine are sold in
      processed forms and thus morphological authentication is almost impossible. With
      herbal industry rapidly growing size, consumer safety becomes an important issue
      that requires special attention. Identification of herbal species in the products
      is therefore needed. METHODS: Sequences from the selected regions (matK, rbcL,
      trnL and ITS1) were retrieved and analysed. Then the most suitable barcode was
      assessed for discrimination of T. crispa from closely related species by HRM
      analysis and used in authentication of commercial products. RESULTS: The ITS1
      barcode was found to be the suitable primer as melting data from the HRM assay
      proved to be capable of distinguishing T. crispa from its related species. The
      developed protocol was then employed to authenticate medicinal products in
      powdered form. HRM analysis of all tested samples here revealed that five out of
      eight products contained not only the indicated species T. crispa but also other
      Tinospora, that have a high level of morphological similarity. CONCLUSION:
      Misrepresentation, poor packaging and inappropriate labeling of the tested
      medicinal herbal products are thought to be the reason of the results here. Using
      Bar-HRM with the ITS marker lead to success in authenticating the tested herbal
      products.

PMID- 29587840
TI  - Risk factors affecting the mortality of HIV-infected patients with pulmonary
      tuberculosis in the cART era: a retrospective cohort study in China.
AB  - BACKGROUND: Tuberculosis infection still places a great burden on HIV-infected
      individuals in China and other developing countries. Knowledge of the survival of
      HIV-infected patients with pulmonary tuberculosis (PTB) would provide important
      insights for the clinical management of this population, which remains to be well
      described in current China. METHODS: HIV-infected patients with PTB admitted to
      Shanghai Public Health Clinical Center from January 2011 to December 2015 were
      retrospectively enrolled. In this cohort, the survival prognosis was estimated by
      the Kaplan-Meier method, while univariate and multivariate Cox proportional
      hazards models were used to determine the risk factors affecting mortality.
      RESULTS: After reviewing 4914 admitted patients with HIV infection, 359 PTB cases
      were identified. At the time of PTB diagnosis, the patients' median CD4+ T cell
      count was 51 /mm3 (IQR: 23-116), and 27.30% of patients (98/359) were on
      combination antiretroviral therapy (cART). For the 333 cases included in the
      survival analysis, the overall mortality was 15.92% (53/333) during a median 27
      month follow-up. The risk factors, including age older than 60 years (HR: 3.18;
      95% CI: 1.66-6.10), complication with bacterial pneumonia (HR: 2.64; 95% CI: 1.30
      5.35), diagnosis delay (HR: 2.60; 95% CI: 1.42-4.78), CD4+ T cell count less than
      50/mm3 (HR: 2.38; 95% CI: 1.27-4.43) and pulmonary atelectasis (HR: 2.20; 95% CI:
      1.05-4.60), might independently contribute to poor survival. Among patients
      without cART before anti-TB treatment, the later initiation of cART (more than 8
      weeks after starting anti-TB treatment) was found to increase the mortality rate
      (OR: 4.33; 95% CI: 1.22-15.36), while the initiation of cART within 4-8 weeks
      after starting anti-TB treatment was associated with the fewest deaths (0/14).
      CONCLUSIONS: The subjects in this study conducted in the cART era were still
      characterized by depressed immunological competence and low rates of cART
      administration, revealing possible intervention targets for preventing TB
      reactivation in HIV-infected individuals under current circumstances.
      Furthermore, our study indicated that the timely diagnosis of PTB, prevention of
      secondary bacterial pneumonia by prophylactic management and optimization of the
      timing of cART initiation could have significant impacts on decreasing mortality
      among HIV/PTB co-infected populations. These findings deserve further prospective
      investigations to optimize the management of HIV/PTB-co-infected patients. TRIAL
      REGISTRATION: NCT01344148 , Registered September 14, 2010.

PMID- 29587841
TI  - Physical activity in the morning and afternoon is lower in patients with chronic
      obstructive pulmonary disease with morning symptoms.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) experience
      symptoms that vary over the day. Symptoms at the start of the day might influence
      physical activity during the rest of the day. Therefore, physical activity during
      the course of the day was studied in patients with low and high morning symptom
      scores. METHODS: This cross-sectional observational study included patients with
      moderate to very severe COPD. Morning symptoms were evaluated with the PRO
      morning COPD Symptoms Questionnaire (range 0-60); the median score was used to
      create two groups (low and high morning symptom scores). Physical activity was
      examined with an accelerometer. Activity parameters during the night, morning,
      afternoon and evening were compared between patients with low and high morning
      symptom scores using independent t-tests or Mann-Whitney U tests. RESULTS:
      Seventy nine patients were included. Patients were aged (mean +/- SD) 65.6 +/-
      8.8 years with a mean forced expiratory volume in 1 s of 55 +/- 17%predicted.
      Patients with low morning symptom scores (score < 17.0) took more steps in the
      afternoon (p = 0.015) and morning (p = 0.030). There were no significant
      differences during the evening and night. CONCLUSION: Patients with high morning
      symptom scores took significantly fewer steps in the morning and afternoon than
      those with low morning symptom scores. Prospective studies are needed to prove
      causality between morning symptoms and physical activity during different parts
      of the day.

PMID- 29587842
TI  - Experimental infection of pigs with H1 and H3 influenza A viruses of swine by
      using intranasal nebulization.
AB  - BACKGROUND: Experimental infection of pigs via direct intranasal or intratracheal
      inoculation has been mainly used to study the infectious process of influenza A
      viruses of swine (IAVs-S). Nebulization is known to be an alternative method for
      inoculating pigs with IAVs-S, because larger quantities of virus potentially can
      be delivered throughout the respiratory tract. However, there is very little data
      on the experimental infection of pigs by inhalation using nebulizer. In the
      current study, we used intranasal nebulization to inoculate pigs with 9 different
      IAVs-S-3 H1N1, 2 H1N2, and 4 H3N2 strains. We then assessed the process of
      infection by evaluating the clinical signs, nasal and oral viral shedding, and
      seroconversion rates of the pigs inoculated. RESULTS: Lethargy and sneezing were
      the predominant clinical signs among pigs inoculated with 7 of the 9 strains
      evaluated; the remaining 2 strains (1 H1N1 and 1 H1N2 isolate) failed to induce
      any clinical signs throughout the experiments. Significantly increased rectal
      temperatures were observed with an H1N1 or H3N2 strains between 1 and 3 days post
      inoculation (dpi). In addition, patterns of nasal viral shedding differed among
      the strains: nasal viral shedding began on 1 dpi for 6 strains, with all 9
      viruses being shed from 2 to 5 dpi. The detection of viral shedding was less
      sensitive from oral samples than nasal secretions. Viral shedding was not
      detected in either nasal or oral swabs after 10 dpi. According to
      hemagglutination-inhibition assays, all inoculated pigs had seroconverted to the
      inoculating virus by 14 dpi, with titers ranging from 10 to 320. CONCLUSIONS: Our
      current findings show that intranasal nebulization successfully established IAV-S
      infections in pigs and demonstrate that clinical signs, viral shedding, and host
      immune responses varied among the strains inoculated.

PMID- 29587843
TI  - Construct validity, test-retest reliability and internal consistency of the Thai
      version of the disabilities of the arm, shoulder and hand questionnaire (DASH-TH)
      in patients with carpal tunnel syndrome.
AB  - OBJECTIVE: This study evaluated additional psychometric properties of the Thai
      version of the disabilities of the arm, shoulder and hand questionnaire (DASH-TH)
      which included, test-retest reliability, construct validity, internal consistency
      of in patients with carpal tunnel syndrome. As for determining construct
      validity, the Thai EuroQOL questionnaire (EQ-5D-5L) was also administered in
      order to examine convergent and divergent validity. RESULTS: Fifty patients
      completed both questionnaires. The DASH-TH showed excellent test-retest
      reliability (intraclass correlation coefficient = 0.811) and internal consistency
      (Cronbach's alpha = 0.911). The exploratory factor analysis yielded a six-factor
      solution while the confirmatory factor analysis denoted that the hypothesized
      model adequately fit the data with a comparative fit index of 0.967 and a Tucker
      Lewis index of 0.964. The related subscales between the DASH-TH and the Thai EQ
      5D-5L were significantly correlated, indicating the DASH-TH's convergent and
      discriminant validity. The DASH-TH demonstrated good reliability, internal
      consistency construct validity, and multidimensionality, in assessing the upper
      extremity function in carpal tunnel syndrome patients.

PMID- 29587844
TI  - From river blindness control to elimination: bridge over troubled water.
AB  - BACKGROUND: An estimated 25 million people are currently infected with
      onchocerciasis (a parasitic infection caused by the filarial nematode Onchocerca
      volvulus and transmitted by Simulium vectors), and 99% of these are in sub
      Saharan Africa. The African Programme for Onchocerciasis Control closed in
      December 2015 and the World Health Organization has established a new structure,
      the Expanded Special Project for the Elimination of Neglected Tropical Diseases
      for the coordination of technical support for activities focused on five
      neglected tropical diseases in Africa, including onchocerciasis elimination.
      AIMS: In this paper we argue that despite the delineation of a reasonably well
      defined elimination strategy, its implementation will present particular
      difficulties in practice. We aim to highlight these in an attempt to ensure that
      they are well understood and that effective plans can be laid to solve them by
      the countries concerned and their international partners. CONCLUSIONS: A specific
      concern is the burden of disease caused by onchocerciasis-associated epilepsy in
      hyperendemic zones situated in countries experiencing difficulties in
      strengthening their onchocerciasis control programmes. These difficulties should
      be identified and programmes supported during the transition from morbidity
      control to interruption of transmission and elimination.

PMID- 29587845
TI  - Patient-derived lymphoblastoid cell lines harboring mitochondrial DNA mutations
      as tool for small molecule drug discovery.
AB  - OBJECTIVE: Mitochondrial diseases are a group of devastating disorders for which
      there is no transformative cure. The majority of therapies for mitochondrial
      disease-approved, previously tested, or currently in development-are small
      molecules. The implementation of better cell-based models of mitochondrial
      disease can accelerate and improve the accuracy of small molecule drug discovery.
      The objective of this study is to evaluate the use of patient-derived
      lymphoblastoid cell lines for small molecule research in mitochondrial disease.
      RESULTS: Five lymphoblastoid cell lines derived from mitochondrial disease
      patients harboring point mutations in mtND1, mtND4, or mtATP6 were characterized
      in two high throughput assays assessing mitochondrial function. In a pilot
      "clinical trial in a dish" experiment, the efficacy of idebenone-an approved
      therapy for mitochondrial disease-on the lymphoblastoid cell lines was tested.
      Idebenone increased the basal respiration of all lymphoblastoid cell lines except
      those harboring the 8993T>G point mutation in mtATP6. Our results posit
      lymphoblastoid cell lines as a strong model for mitochondrial disease research
      with small molecules and have implications for the clinical efficacy of
      idebenone.

PMID- 29587846
TI  - Evaluation of two DNA extraction methods for the PCR-based detection of
      eukaryotic enteric pathogens in fecal samples.
AB  - OBJECTIVE: Efficient and easy-to-use DNA extraction and purification methods are
      critical in implementing PCR-based diagnosis of pathogens. In order to optimize
      the routine clinical laboratory diagnosis of eukaryotic enteric pathogens, we
      compare, via quantitative PCR cycle threshold (Ct) values, the efficiency of two
      DNA extraction kits: the semi-automated EZ1(r) (Qiagen) and the manual QIAamp(r)
      DNA Stool Mini Kit (Qiagen), on six protozoa: Blastocystis spp., Cryptosporidium
      parvum/hominis, Cyclospora cayetanensis, Dientamoeba fragilis, Giardia
      intestinalis and Cystoisospora belli and one microsporidia: Enterocytozoon
      bieneusi. RESULTS: Whereas EZ1(r) (Qiagen) and QIAamp(r) DNA Stool Mini Kit
      (Qiagen) yielded similar performances for the detection of Cryptosporidium spp.
      and D. fragilis, significant lower Ct values (p < 0.002) pointed out a better
      performance of EZ1(r) on the five remaining pathogens. DNA extraction using the
      semi-automated EZ1(r) procedure was faster and as efficient as the manual
      procedure in the seven eukaryotic enteric pathogens tested. This procedure is
      suitable for DNA extraction from stools in both clinical laboratory diagnosis and
      epidemiological study settings.

PMID- 29587848
TI  - Cytokeratin 5/6 expression in bladder cancer: association with clinicopathologic
      parameters and prognosis.
AB  - OBJECTIVES: Well differentiated keratinized squamous component as a part of
      urothelial carcinoma can be easily appreciated; however non-keratinizing squamous
      differentiation closely resembles urothelial differentiation. In addition
      prognostic significance of CK 5/6 expression in the absence of apparent squamous
      differentiation is still unclear. Therefore, in the present study we aimed to
      evaluate the frequency of CK 5/6 expression in 127 cases of urothelial carcinoma
      and its prognostic significance in loco-regional population. RESULTS: Positive
      CK5/6 expression was noted in 6.3% (8 cases) and 13.4% (17 cases) revealed focal
      positive CK 5/6 expression. On the other hand, 80.3% (102 cases) showed negative
      CK5/6 staining. Significant association of CK5/6 expression was noted with tumor
      grade and muscularis propria invasion, however no significant association was
      noted with overall and disease free survival. On the basis of the results of our
      study we can conclude that CK5/6 is an independent prognostic biomarker in
      urothelial carcinoma and therefore can be used in the prognostic stratification
      of the patients with bladder cancer.

PMID- 29587847
TI  - High-sensitivity virus and mycoplasma screening test reveals high prevalence of
      parvovirus B19 infection in human synovial tissues and bone marrow.
AB  - BACKGROUND: Latent microorganism infection is a safety concern for the clinical
      application of mesenchymal stem cells (MSCs). The aim of this study is to
      investigate the frequencies and sensitivities of the latent virus and mycoplasma
      infections in synovium, bone marrow, peripheral blood cells, and blood plasma and
      cultured synovial MSCs. METHODS: Total DNA and RNA of the synovium (n = 124),
      bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14
      day cultured synovial MSCs (n = 63) were collected from patients who underwent
      total knee arthroplasty or anterior ligament reconstruction after written
      informed consents were obtained. The multiplex polymerase chain reaction (PCR)
      primers were designed to quantitatively measure the representative genomes of 13
      DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and
      virus spike test were also performed to demonstrate the sensitivity of synovial
      MSCs to the candidate pathogens. RESULTS: In synovium and bone marrow, the
      positive rates of parvovirus B19 genome were significantly higher than in
      peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment
      analysis of amplified and sequenced viral target genes showed the proximity of
      the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs
      cultured for 14 days were positive for virus infection only in two patients (2/62
      = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples.
      Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex
      virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. CONCLUSION:
      This study revealed a relatively high incidence of latent parvovirus B19 in
      synovium and bone marrow tissue.

PMID- 29587849
TI  - Serological survey in wild boar (Sus scrofa) in Switzerland and other European
      countries: Sarcoptes scabiei may be more widely distributed than previously
      thought.
AB  - BACKGROUND: Sarcoptic mange has recently emerged in wild boar in Switzerland,
      raising the question of the origin of the infection. The main aim of this study
      was to assess the extent of exposure of the wild boar populations to Sarcoptes
      scabiei in Switzerland, prior to and after the detection of mange cases, to
      determine whether the mite has been recently introduced into the populations
      concerned. We performed a serological survey using a commercially available ELISA
      and 1056 archived blood samples of free-ranging wild boar from Switzerland. To
      facilitate the interpretation of the obtained data, we additionally estimated
      seroprevalence in wild boar populations of four other European countries (1060
      samples), both from areas with confirmed clinical cases of mange and from areas
      without reported cases in wild boar. Lastly, we revised the evaluation of the
      commercial ELISA when used with wild boar sera. RESULTS: Seropositive reactions
      were observed for samples from all five countries and from 15 of the 16 study
      areas. The obtained apparent seroprevalences ranged from 0.0% (0/82; 95%
      confidence interval [CI]: 0.0-4.4) to 17.4% (8/46; 95% CI: 7.8-31.4). Wild boar
      from study areas with known clinical cases and those <=60 kg were four times more
      likely to be seropositive than wild boar from areas without reported cases and >
      60 kg, respectively. Optical density values did not differ between the two types
      of study areas among seropositive samples but were significantly lower among
      seronegative samples from areas without than from areas with clinical cases. No
      difference was observed between the two sampling periods in Switzerland. The
      revised ELISA specificity was 96.8% (984/1017; 95% CI: 95.5-97.7) when wild boar
      from areas without history of mange were considered truly negative. CONCLUSIONS:
      Seropositivity to S. scabiei is more frequent and occurs over a larger geographic
      range than expected. Data suggest that the parasite is endemic within the wild
      boar populations of Switzerland and other European countries but that its
      presence is not necessarily associated with disease occurrence. Extrinsic factors
      which trigger disease emergence in infected populations remain to be
      investigated. The applied ELISA represents a promising tool for future studies.

PMID- 29587851
TI  - Clinical and MRI remission in patients with nonradiographic axial
      spondyloarthritis who received long-term open-label adalimumab treatment: 3-year
      results of the ABILITY-1 trial.
AB  - BACKGROUND: Adalimumab was effective in treating patients with nonradiographic
      axial spondyloarthritis (nr-axSpA) in the 12-week ABILITY-1 trial. We present
      long-term efficacy and safety results of adalimumab from the open-label ABILITY-1
      extension, including the relationship between clinical and magnetic resonance
      imaging (MRI) remission and impact of sustained clinical remission on physical
      function. METHODS: Patients received adalimumab 40 mg every other week or placebo
      for 12 weeks, then open-label adalimumab for up to 144 weeks. Clinical and safety
      data were collected through 3 years, and MRI data were collected until 2 years.
      Analyses were performed in the total population and subpopulation with positive
      MRI and/or elevated C-reactive protein (MRI/CRP-positive) at baseline. Clinical
      and MRI remission definitions included Ankylosing Spondylitis Disease Activity
      Score inactive disease (ASDAS ID; score < 1.3) and Spondyloarthritis Research
      Consortium of Canada (SPARCC) MRI score < 2 for sacroiliac joints (SIJs), spine,
      or both. Physical function was assessed using the Bath Ankylosing Spondylitis
      Functional Index. RESULTS: Overall, 185 patients were included in the total
      population and 142 in the MRI/CRP-positive subpopulation; 65% and 68%,
      respectively, completed 3 years. Clinical, functional, and MRI improvements were
      similar and equally sustainable in both populations. At year 3, the percentages
      of patients in ASDAS ID in the MRI/CRP-positive subpopulation were 30%/33%
      (nonresponder imputation) and 46%/49% (observed) for those initially receiving
      adalimumab/placebo. At years 1 and 2, patients in ASDAS ID vs not had
      significantly greater improvements in SPARCC SIJ scores from baseline (P <
      0.001). Among patients with baseline MRI scores >= 2 who achieved ASDAS ID at
      year 2, 44-68% also had MRI remission. Significantly more patients with sustained
      ASDAS ID through year 2 or 3 vs without achieved normal physical function (100%
      vs 48%; 100% vs 44%; both P < 0.001). No new safety concerns were observed.
      CONCLUSIONS: In the ABILITY-1 study of nr-axSpA, adalimumab therapy provided
      sustained clinical and functional improvements through 3 years, as well as
      suppression of MRI axial inflammation, which was greater in patients who achieved
      clinical remission. Sustained clinical remission was associated with increased
      attainment of normal physical function. The safety profile of adalimumab was
      consistent with prior studies. TRIAL REGISTRATION: ClinicalTrials.gov ,
      NCT00939003 ; registered on July 10, 2009.

PMID- 29587850
TI  - Investigation of temperature conditions in Swiss urban and suburban microhabitats
      for the overwintering suitability of diapausing Aedes albopictus eggs.
AB  - BACKGROUND: In Switzerland, the invasive Asian tiger mosquito, Aedes albopictus,
      is firmly established in the Canton of Ticino, south of the Alps. According to a
      large-scale distribution model developed in 2013, suitable climatic conditions
      for the establishment of Ae. albopictus north of the Alps are found in Basel and
      Geneva while Zurich appears to be characterized by winters currently being too
      cold for survival of diapausing eggs. However, the spatial resolution of large
      scale distribution models might not be sufficient to detect particular climatic
      conditions existing in urban settings, such as the presence of microclimatic
      temperatures, which may positively influence the probability of diapausing eggs
      to overwinter. In order to investigate this, microclimatic monitoring of
      potential diapausing sites (i.e. catch basins) and external controls was
      performed in January 2017 in Ticino and within the cities of Basel, Geneva and
      Zurich. RESULTS: Mean January temperatures in catch basins of Basel, Geneva and
      Zurich were always higher than the -1  degrees C temperature threshold previously
      set for survival probability of diapausing eggs, while mean January temperatures
      were below -1  degrees C in several catch basins south of the Alps, where Ae.
      albopictus eggs currently overwinter. The catch basin absolute January daily
      minimum temperatures both south and north of the Alps were in general higher than
      the external control temperatures. Absolute January daily minimum temperatures in
      catch basins in Basel, Geneva and Zurich were always above -10  degrees C,
      indicating that diapausing Ae. albopictus eggs could potentially survive winter
      nights in urban areas north of the Alps. CONCLUSIONS: The findings confirmed
      previous conclusions that urban catch basins can provide favourable conditions
      for overwintering of diapausing eggs compared to more cold-exposed sites. The
      results confirmed the presence of suitable winter conditions for the
      establishment of Ae. albopictus in the cities of Basel and Geneva. In addition,
      the microclimate-scale analysis added new information compared to the previous
      large-scale prevision model by showing that also the city of Zurich could provide
      winter conditions suitable for the establishment of Ae. albopictus. This
      illustrates the importance of the resolution of climate data in using models to
      predict Ae. albopictus distribution.

PMID- 29587852
TI  - Repair of bone defects in rat radii with a composite of allogeneic adipose
      derived stem cells and heterogeneous deproteinized bone.
AB  - BACKGROUND: In the bone tissue engineering domain, seed cells, scaffold and cell
      scaffold composites are three focuses. In this study, the feasibility of using
      allogeneic adipose-derived stem cells(ADSCs) combined with heterogeneous
      deproteinized bone (HDB) to repair segmental radial defects was investigated by
      observing the repair of the defect area. METHODS: ADSCs were cultured in vitro,
      purified, antigen-detected and osteogenic differentiation potency-measured; then,
      the ADSCs of the third generation were seeded into HDB to prepare an ADSCs-HDB
      composite partly with osteogenesis induced cells. Sixty Wistar rats were randomly
      divided into four groups with 15 in each group. A bone defect (4 mm in length)
      was created at the left radius in each rat. Two kinds of ADSCs-HDB composites
      were implanted in the ADSCs osteogenesis group or ADSCs group; HDB was implanted
      in the negative control group; nothing was filled in the blank control group. The
      bone defect repair was evaluated by gross observation, molybdenum target X-ray
      examination and histological analyses after surgery. RESULTS: Gross observation:
      the bone defect area was completely filled and difficult to recognize in the
      ADSCs osteogenesis group. The connection of the ADSCs group was strong, but the
      implants were clearly identifiable. The joints of the negative control group were
      slightly thick but the connection was unstable. In the blank control group,
      kermesinus tissue was between the two ends and bones were not connected after 8
      weeks. Molybdenum target X-ray examinations: In the ADSCs osteogenesis group,
      evident bridges in the graft were observed in the defects in the fourth week; the
      defects were filled with new bone completely and a marrow cavity appeared at 8
      weeks. In the ADSCs group, there were some callus formations, but the radial
      defect was still obvious at 8 weeks. In the negative control group, fracture
      lines were clear. In the blank control group, no osseous bridges were observed,
      which resulted in bone nonunion eventually in 8 weeks. There were significant
      differences in the callus density between experimental groups and the blank
      control group at 4 and 8 weeks (P < 0.01). Histological measures showed that the
      rate and quality of the new bone formation and remodelling was significantly
      different between the experimental and control groups. CONCLUSIONS: A composite
      of ADSCs-HDB has a strong osteogenic ability. It can repair segmental bone
      defects well and is promising to serve as grafting material in bone tissue
      engineering.

PMID- 29587854
TI  - Large-scale discovery of previously undetected microRNAs specific to human liver.
AB  - MicroRNAs (miRNAs) are crucial regulators of gene expression in normal
      development and cellular homeostasis. While miRNA repositories contain thousands
      of unique sequences, they primarily contain molecules that are conserved across
      several tissues, largely excluding lineage and tissue-specific miRNAs. By
      analyzing small non-coding RNA sequencing data for abundance and secondary RNA
      structure, we discovered 103 miRNA candidates previously undescribed in liver
      tissue. While expression of some of these unannotated sequences is restricted to
      non-malignant tissue, downregulation of most of the sequences was detected in
      liver tumors, indicating their importance in the maintenance of liver
      homeostasis. Furthermore, target prediction revealed the involvement of the
      unannotated miRNA candidates in fatty-acid metabolism and tissue regeneration,
      which are key pathways in liver biology. Here, we provide a comprehensive
      analysis of the undiscovered liver miRNA transcriptome, providing new resources
      for a deeper exploration of organ-specific biology and disease.

PMID- 29587853
TI  - What do randomized controlled trials say about virtual rehabilitation in stroke?
      A systematic literature review and meta-analysis of upper-limb and cognitive
      outcomes.
AB  - BACKGROUND: Virtual-reality based rehabilitation (VR) shows potential as an
      engaging and effective way to improve upper-limb function and cognitive abilities
      following a stroke. However, an updated synthesis of the literature is needed to
      capture growth in recent research and address gaps in our understanding of
      factors that may optimize training parameters and treatment effects. METHODS:
      Published randomized controlled trials comparing VR to conventional therapy were
      retrieved from seven electronic databases. Treatment effects (Hedge's g) were
      estimated using a random effects model, with motor and functional outcomes
      between different protocols compared at the Body Structure/Function, Activity,
      and Participation levels of the International Classification of Functioning.
      RESULTS: Thirty-three studies were identified, including 971 participants (492 VR
      participants). VR produced small to medium overall effects (g = 0.46; 95% CI:
      0.33-0.59, p < 0.01), above and beyond conventional therapies. Small to medium
      effects were observed on Body Structure/Function (g = 0.41; 95% CI: 0.28-0.55; p
      < 0.01) and Activity outcomes (g = 0.47; 95% CI: 0.34-0.60, p < 0.01), while
      Participation outcomes failed to reach significance (g = 0.38; 95% CI: -0.29
      1.04, p = 0.27). Superior benefits for Body Structure/Function (g = 0.56) and
      Activity outcomes (g = 0.62) were observed when examining outcomes only from
      purpose-designed VR systems. Preliminary results (k = 4) suggested small to
      medium effects for cognitive outcomes (g = 0.41; 95% CI: 0.28-0.55; p < 0.01).
      Moderator analysis found no advantage for higher doses of VR, massed practice
      training schedules, or greater time since injury. CONCLUSION: VR can effect
      significant gains on Body Structure/Function and Activity level outcomes,
      including improvements in cognitive function, for individuals who have sustained
      a stroke. The evidence supports the use of VR as an adjunct for stroke
      rehabilitation, with effectiveness evident for a variety of platforms, training
      parameters, and stages of recovery.

PMID- 29587856
TI  - Global Health as "umbrella term" - a qualitative study among Global Health
      teachers in German medical education.
AB  - BACKGROUND: The increasing impact of globalisation on healthcare demands new
      knowledge, skills and attitudes from healthcare professionals. One consequence of
      this is the rise of Global Health (GH) programs in health education all over the
      world. In Germany no consensus exists on what GH is and how it should be taught.
      This study used a grounded theory approach. We conducted eleven in-depth
      interviews with GH teachers in German medical education to ask them about their
      views on Global Health and the approaches they took in teaching these topics.
      Data collection and Analysis informed each other and followed an inductive
      approach. RESULTS: Our research identified three major questions: (1) What is GH?
      (2) What belongs to GH? (3) How can GH be taught? A central finding of our study
      is the understanding of GH as an umbrella term. We show how this understanding
      helps clarify the relation between GH and Public Health, International Health and
      Tropical medicine. At the core of GH we see the supraterritorial determinants of
      health. Surrounding the core, we describe a wide variety of topics that are a
      facultative, but not necessarily a compulsory part GH. One of the key
      characteristics of GH within all its aspects is its multidisciplinary nature.
      Based on this understanding we present models about the content of GH, how it can
      be taught and how GH teaching improves and strengthens overall medical education.
      CONCLUSIONS: This is to our knowledge the first study that conducts in-depth
      interviews with GH teachers to explore the practical understanding of GH in
      medical education. While the generalisability of our results needs to be subject
      of further research, the models presented can help shape the future discourse
      around GH and its integration into medical education.

PMID- 29587855
TI  - Assessment of microbiome changes after rumen transfaunation: implications on
      improving feed efficiency in beef cattle.
AB  - BACKGROUND: Understanding the host impact on its symbiotic microbiota is
      important in redirecting the rumen microbiota and thus improving animal
      performance. The current study aimed to understand how rumen microbiota were
      altered and re-established after being emptied and receiving content from donor,
      thus to understand the impact of such process on rumen microbial fermentation and
      to explore the microbial phylotypes with higher manipulation potentials. RESULTS:
      Individual animal had strong effect on the re-establishment of the bacterial
      community according to the observed profiles detected by both fingerprinting and
      pyrosequencing. Most of the bacterial profile recovery patterns and extents at
      genus level varied among steers; and each identified bacterial genus responded to
      transfaunation differently within each host. Coriobacteriaceae, Coprococcus, and
      Lactobacillus were found to be the most responsive and tunable genera by
      exchanging rumen content. Besides, the association of 18 bacterial phylotypes
      with host fermentation parameters suggest that these phylotypes should also be
      considered as the regulating targets in improving host feed efficiency. In
      addition, the archaeal community had different re-establishment patterns for each
      host as determined by fingerprint profiling: it was altered after receiving non
      native microbiome in some animals, while it resumed its original status after the
      adaptation period in the other ones. CONCLUSIONS: The highly individualized
      microbial re-establishment process suggested the importance of considering host
      genetics, microbial functional genomics, and host fermentation/performance
      assessment when developing effective and selective microbial manipulation methods
      for improving animal feed efficiency.

PMID- 29587857
TI  - HSP70 from the Antarctic sea urchin Sterechinus neumayeri: molecular
      characterization and expression in response to heat stress.
AB  - BACKGROUND: Heat stress proteins are implicated in stabilizing and refolding
      denatured proteins in vertebrates and invertebrates. Members of the Hsp70 gene
      family comprise the cognate heat shock protein (Hsc70) and inducible heat shock
      protein (Hsp70). However, the cDNA sequence and the expression of Hsp70 in the
      Antarctic sea urchin are unknown. METHODS: We amplified and cloned a transcript
      sequence of 1991 bp from the Antarctic sea urchin Sterechinus neumayeri,
      experimentally exposed to heat stress (5  and 10  degrees C for 1, 24 and 48 h).
      RACE-PCR and qPCR were employed to determine Hsp70 gene expression, while western
      blot and ELISA methods were used to determine protein expression. RESULTS: The
      sequence obtained from S. neumayeri showed high identity with Hsp70 members.
      Several Hsp70 family features were identified in the deduced amino acid sequence
      and they indicate that the isolated Hsp70 is related to the cognate heat shock
      protein type. The corresponding 70 kDa protein, called Sn-Hsp70, was immune
      detected in the coelomocytes and the digestive tract of S. neumayeri using a
      monospecific polyclonal antibody. We showed that S. neumayeri do not respond to
      acute heat stress by up-regulation of Sn-Hsp70 at transcript and protein level.
      Furthermore, the Sn-Hsp70 protein expression was not induced in the digestive
      tract. CONCLUSIONS: Our results provide the first molecular evidence that Sn
      Hsp70 is expressed constitutively and is non-induced by heat stress in S.
      neumayeri.

PMID- 29587858
TI  - HLA and proteasome expression body map.
AB  - BACKGROUND: The presentation of HLA peptide complexes to T cells is a highly
      regulated and tissue specific process involving multiple transcriptionally
      controlled cellular components. The extensive polymorphism of HLA genes and the
      complex composition of the proteasome make it difficult to map their expression
      profiles across tissues. METHODS: Here we applied a tailored gene quantification
      pipeline to 4323 publicly available RNA-Seq datasets representing 55 normal
      tissues and cell types to examine expression profiles of (classical and non
      classical) HLA class I, class II and proteasomal genes. RESULTS: We generated the
      first comprehensive expression atlas of antigen presenting-related genes across
      56 normal tissues and cell types, including immune cells, pancreatic islets,
      platelets and hematopoietic stem cells. We found a surprisingly heterogeneous HLA
      expression pattern with up to 100-fold difference in intra-tissue median HLA
      abundances. Cells of the immune system and lymphatic organs expressed the highest
      levels of classical HLA class I (HLA-A,-B,-C), class II (HLA-DQA1,-DQB1,-DPA1,
      DPB1,-DRA,-DRB1) and non-classical HLA class I (HLA-E,-F) molecules, whereas
      retina, brain, muscle, megakaryocytes and erythroblasts showed the lowest
      abundance. In contrast, we identified a distinct and highly tissue-restricted
      expression pattern of the non-classical class I gene HLA-G in placenta,
      pancreatic islets, pituitary gland and testis. While the constitutive proteasome
      showed relatively constant expression across all tissues, we found the
      immunoproteasome to be enriched in lymphatic organs and almost absent in immune
      privileged tissues. CONCLUSIONS: Here, we not only provide a reference catalog of
      tissue and cell type specific HLA expression, but also highlight extremely
      variable expression of the basic components of antigen processing and
      presentation in different cell types. Our findings indicate that low expression
      of classical HLA class I molecules together with lack of immunoproteasome
      components as well as upregulation of HLA-G may be of key relevance to maintain
      tolerance in immune privileged tissues.

PMID- 29587859
TI  - Characterization of tri and tetra-nucleotide microsatellite loci for the
      freshwater snails Promenetus exacuous (Planorbidae) and Valvata tricarinata
      (Valvatidae) and their utility in population genetic studies.
AB  - OBJECTIVE: Promenetus exacuous and Valvata tricarinata are freshwater snail
      species with widespread distributions throughout North America. Information
      regarding their genetic diversity and population connectivity are currently
      lacking. We utilized next generation sequencing to develop the first
      microsatellites for each species to investigate genetic diversity within and
      differentiation among populations. RESULTS: Sixteen and seventeen microsatellite
      loci were developed for P. exacuous and V. tricarinata, respectively, and tested
      in a total of 43 P. exacuous and 48 V. tricarinata from two lakes approximately
      183 km apart in New York State, USA. Fifteen P. exacuous loci were polymorphic in
      at least one lake and possessed 1-23 alleles and observed heterozygosities of
      0.00-0.96 within individual lakes. Seventeen polymorphic V. tricarinata loci
      possessed 2-19 alleles and observed heterozygosities of 0.04-0.96 within lakes.
      Bayesian clustering using 12 loci for each species identified two distinct
      genetic populations, reflecting the two lakes. High assignment scores for
      individual snails to the lakes they were collected from supported strong
      population structure with minimal admixture at the scale of this study. These
      loci will be useful for investigating the genetic diversity and population
      structure of these species and indicate genetic differentiation may be common
      among their populations.

PMID- 29587860
TI  - Roles of astrocytic connexin-43, hemichannels, and gap junctions in oxygen
      glucose deprivation/reperfusion injury induced neuroinflammation and the possible
      regulatory mechanisms of salvianolic acid B and carbenoxolone.
AB  - BACKGROUND: Glia-mediated neuroinflammation is related to brain injury
      exacerbation after cerebral ischemia/reperfusion (I/R) injury. Astrocytic
      hemichannels or gap junctions, which were mainly formed by connexin-43, have been
      implicated in I/R damage. However, the exact roles of astrocytic hemichannels and
      gap junction in neuroinflammatory responses induced by I/R injury remain unknown.
      METHODS: Primary cultured astrocytes were subjected to OGD/R injury, an in vitro
      model of I/R injury. Salvianolic acid B (SalB) or carbenoxolone (CBX) were
      applied for those astrocytes. Besides, Cx43 mimetic peptides Gap19 or Gap26 were
      also applied during OGD/R injury; Cx43 protein levels were determined by western
      blot and cytoimmunofluorescene staining, hemichannel activities by Ethidium
      bromide uptake and ATP concentration detection, and gap junction intercellular
      communication (GJIC) permeability by parachute assay. Further, astrocyte
      conditioned medium (ACM) was collected and incubated with microglia. Meanwhile,
      ATP or apyrase were applied to explore the role of ATP during OGD/R injury.
      Microglial activation, M1/M2 phenotypes, and M1/M2-related cytokines were
      detected. Also, microglia-conditioned medium (MEM) was collected and incubated
      with astrocytes to further investigate its influence on astrocytic hemichannel
      activity and GJIC permeability. Lastly, effects of ACM and MCM on neuronal
      viability were detected by flow cytometry. RESULTS: We found that OGD/R induced
      abnormally opened hemichannels with increased ATP release and EtBr uptake but
      reduced GJIC permeability. WB tests showed decreased astrocytic plasma membrane's
      Cx43, while showing an increase in cytoplasma. Treating OGD/R-injured microglia
      with ATP or OGD/R-ACM induced further microglial activation and secondary pro
      inflammatory cytokine release, with the M1 phenotype predominating. Conversely,
      astrocytes incubated with OGD/R-MCM exhibited increased hemichannel opening but
      reduced GJIC coupling. Both SalB and CBX inhibited abnormal astrocytic
      hemichannel opening and ATP release and switched the activated microglial
      phenotype from M1 to M2, thus providing effective neuroprotection. Application of
      Gap19 or Gap26 showed similar results with CBX. We also found that OGD/R injury
      caused both plasma membrane p-Cx43(Ser265) and p-Src(Tyr416) significantly
      upregulated; application of SalB may be inhibiting Src kinase and attenuating
      Cx43 internalization. Meanwhile, CBX treatment induced obviously downregulation
      of p-Cx43(Ser368) and p-PKC(Ser729) protein levels in plasma membrane.
      CONCLUSIONS: We propose a vicious cycle exists between astrocytic hemichannel and
      microglial activation after OGD/R injury, which would aggravate neuroinflammatory
      responses and neuronal damage. Astrocytic Cx43, hemichannels, and GJIC play
      critical roles in OGD/R injury-induced neuroinflammatory responses; treatment
      differentially targeting astrocytic Cx43, hemichannels, and GJIC may provide
      novel avenues for therapeutics during cerebral I/R injury.

PMID- 29587861
TI  - Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in
      low-prognosis young women with decreased ovarian reserve: a randomized controlled
      trial.
AB  - BACKGROUND: Management of women with reduced ovarian reserve or poor ovarian
      response (POR) to stimulation is one of the major challenges in reproductive
      medicine. The primary causes of POR remain elusive and oxidative stress was
      proposed as one of the important contributors. It has been suggested that focus
      on the specific subpopulations within heterogeneous group of poor responders
      could assist in evaluating optimal management strategies for these patients. This
      study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10)
      on ovarian response and embryo quality in young low-prognosis patients with POR.
      METHODS: This prospective, randomized controlled study included 186 consecutive
      patients with POR stratified according to the POSEIDON classification group 3
      (age < 35, poor ovarian reserve parameters). The participants were randomized to
      the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment.
      The number of high quality embryos was a primary outcome measure. RESULTS: A
      total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls);
      17 women were excluded due to low compliance with CoQ10 administration. The
      baseline demographic and clinical characteristics were comparable between the
      groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin
      requirements and higher peak E2 levels. Women in CoQ10 group had increased number
      of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more
      high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated
      with CoQ10 had cancelled embryo transfer because of poor embryo development than
      controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had
      available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical
      pregnancy and live birth rates per embryo transfer and per one complete
      stimulation cycle tended to be higher in CoQ10 group but did not achieve
      statistical significance. CONCLUSION: Pretreatment with CoQ10 improves ovarian
      response to stimulation and embryological parameters in young women with poor
      ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether
      there is an effect on clinical treatment endpoints.

PMID- 29587862
TI  - Trauma facilities in Denmark - a nationwide cross-sectional benchmark study of
      facilities and trauma care organisation.
AB  - BACKGROUND: Trauma is a leading cause of death among adults aged < 44 years, and
      optimal care is a challenge. Evidence supports the centralization of trauma
      facilities and the use multidisciplinary trauma teams. Because knowledge is
      sparse on the existing distribution of trauma facilities and the organisation of
      trauma care in Denmark, the aim of this study was to identify all Danish
      facilities that care for traumatized patients and to investigate the diversity in
      organization of trauma management. METHODS: We conducted a systematic
      observational cross-sectional study. First, all hospitals in Denmark were
      identified via online services and clarifying phone calls to each facility.
      Second, all trauma care manuals on all facilities that receive traumatized
      patients were gathered. Third, anesthesiologists and orthopedic surgeons on call
      at all trauma facilities were contacted via telephone for structured interviews.
      RESULTS: A total of 22 facilities in Denmark were found to receive traumatized
      patients. All facilities used a trauma care manual and all had a
      multidisciplinary trauma team. The study found three different trauma team
      activation criteria and nine different compositions of teams who participate in
      trauma care. Training was heterogeneous and, beyond the major trauma centers,
      databases were only maintained in a few facilities. CONCLUSION: The study
      established an inventory of the existing Danish facilities that receive
      traumatized patients. The trauma team activation criteria and the trauma teams
      were heterogeneous in both size and composition. A national database for
      traumatized patients, research on nationwide trauma team activation criteria, and
      team composition guidelines are all called for.

PMID- 29587863
TI  - Chinese herbal medicine Shenzhuo Formula treatment in patients with
      macroalbuminuria secondary to diabetic kidney disease: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Diabetic kidney disease (DKD) is a serious complication associated
      with diabetes mellitus and can cause end-stage renal disease (ESRD). Traditional
      Chinese medicine (TCM) is widely used in China to treat DKD, and in particular
      microalbuminuria and macroalbuminuria. This study will address the efficacy and
      safety of Shenzhuo Formula (SZF), a frequently prescribed TCM, in DKD patients
      with macroalbuminuria. METHODS/DESIGN: This study is a 24-week, randomized, multi
      center, double-blinded, double-dummy, controlled, clinical trial that will
      include 120 DKD patients aged 18 to 80 years old with a 24-h urinary protein (24
      h UP) level of between 0.5 g and 3 g and serum creatinine (SCr) <= 133 MUmol/L
      (1.5 mg/dL) and compare SZF to irbesartan. The 24-h UP change from baseline to
      week 24 will represent the primary endpoint with secondary endpoints including
      SCr, estimated glomerular filtration rate (eGFR), TCM symptoms, urinary albumin
      excretion rate (UAER), etc. Safety assessments will also be evaluated.
      DISCUSSION: This study will provide initial evidence regarding the efficacy and
      safety of SZF relative to irbesartan in the treatment of DKD patients with
      macroalbuminuria. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR
      ICR-15006311 . Registered on 15 April 2015.

PMID- 29587865
TI  - Distinctive features of immunostaining and mutational load in primary pulmonary
      enteric adenocarcinoma: implications for differential diagnosis and
      immunotherapy.
AB  - BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is an extremely rare
      variant of invasive lung cancer. It is highly heterogeneous while shares some
      common morphologic and immunohistochemical features with usual pulmonary
      adenocarcinoma (PAC) and colorectal adenocarcinoma (CRAC), making the
      differential diagnosis difficult. At present there are only limited studies about
      distinctive features of primary PEAC and the results are often inconsistent.
      METHODS: We retrospectively analyzed total 129 primary PEACs and 50 CRACs that
      were published since 1991 or diagnosed in our centre. Among them eight typical
      samples of primary PEACs and usual PACs were detected by targeted exome
      sequencing. RESULTS: The combination of CK7+/CDX2+ acquires high sensitivity
      (71.3%) and specificity (82%) in differential diagnosis of PEACs from CRAC. The
      primary PEACs harbor a high incidence of KRAS mutation but almost absent of EGFR
      mutation. Moreover, compared with usual PACs, the primary PEACs have higher
      nonsynonymous tumor mutation burden and more frequent MMR mutation. CONCLUSIONS:
      The combination of CK7+/CDX2+ immunostaining and the distinctive genetic
      signatures, including low incidence of sensitivity genes mutations and high tumor
      mutation burden, is an important supplementary to the clinical differential
      diagnosis of primary PEACs. Our findings thus have significant implications for
      development of individualized treatment strategy in these patients.

PMID- 29587864
TI  - Outcome Measures in Rheumatology - Interventions for medication Adherence
      (OMERACT-Adherence) Core Domain Set for Trials of Interventions for Medication
      Adherence in Rheumatology: 5 Phase Study Protocol.
AB  - BACKGROUND: Over the last 20 years, there have been marked improvements in the
      availability of effective medications for rheumatic conditions such as gout,
      osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in
      disease flares and the risk of re-fracture in osteoporosis, and the slowing of
      disease progression in RA. However, medication adherence remains suboptimal, as
      treatment regimens can be complex and difficult to continue long term. Many
      trials have been conducted to improve adherence to medication. Core domains,
      which are the outcomes of most relevance to patients and clinicians, are a
      pivotal component of any trial. These core domains should be measured
      consistently, so that all relevant trials can be combined in systematic reviews
      and meta-analyses to reach conclusions that are more valid. Failure to do this
      severely limits the potential for trial-based evidence to inform decisions on how
      to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) -
      Interventions for Medication Adherence study by the OMERACT-Adherence Group aims
      to develop a core domain set for interventions that aim to support medication
      adherence in rheumatology. METHODS/DESIGN: This OMERACT-Adherence study has five
      phases: (1) a systematic review to identify outcome domains that have been
      reported in interventions focused on supporting medication adherence in
      rheumatology; (2) semi-structured stakeholder interviews with patients and
      caregivers to determine their views on the core domains; (3) focus groups using
      the nominal group technique with patients and caregivers to identify and rank
      domains that are relevant to them, including the reasons for their choices; (4)
      an international three-round modified Delphi survey involving patients with
      diverse rheumatic conditions, caregivers, health professionals, researchers and
      other stakeholders to develop a preliminary core domain set; and (5) a
      stakeholder workshop with OMERACT members to review, vote on and reach a
      consensus on the core domain set for interventions to support medication
      adherence in rheumatology. DISCUSSION: Establishing a core domain set to be
      reported in all intervention studies undertaken to support patients with
      medication adherence will enhance the relevance and the impact of these results
      and improve the lives of people with rheumatic conditions.

PMID- 29587866
TI  - miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42
      axis.
AB  - BACKGROUND: Our previous work showed that some Rho GTPases, including Rho, Rac1
      and Cdc42, play critical roles in gastric cancer (GC); however, how they are
      regulated in GC remains largely unknown. In this study, we aimed to investigate
      the roles and molecular mechanisms of Dock6, an atypical Rho guanine nucleotide
      exchange factor (GEF), in GC metastasis. METHODS: The expression levels of Dock6
      and miR-148b-3p in GC tissues and paired nontumor tissues were determined by
      immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. The
      correlation between Dock6/miR-148b-3p expression and the overall survival of GC
      patients was calculated by the Kaplan-Meier method and log-rank test. The roles
      of Dock6 and miR-148b-3p in GC were investigated by in vitro and in vivo
      functional studies. Rac1 and Cdc42 activation was investigated by GST pull-down
      assays. The inhibition of Dock6 transcription by miR-148b-3p was determined by
      luciferase reporter assays. RESULTS: A significant increase in Dock6 expression
      was found in GC tissues compared with nontumor tissues, and its positive
      expression was associated with lymph node metastasis and a higher TNM stage.
      Patients with positive Dock6 expression exhibited shorter overall survival
      periods than patients with negative Dock6 expression. Dock6 promoted GC migration
      and invasion by increasing the activation of Rac1 and Cdc42. miR-148b-3p
      expression was negatively correlated with Dock6 expression in GC, and it
      decreased the motility of GC cells by inhibiting the Dock6/Rac1/Cdc42 axis.
      CONCLUSIONS: Dock6 was over-expressed in GC tissues, and its positive expression
      was associated with GC metastasis and indicated poor prognosis of GC patients.
      Targeting of Dock6 by miR-148b-3p could activate Rac1 and Cdc42, directly
      affecting the motility of GC cells. Targeting the Dock6-Rac1/Cdc42 axis could
      serve as a new therapeutic strategy for GC treatment.

PMID- 29587867
TI  - Group consensus peer review in radiation oncology: commitment to quality.
AB  - BACKGROUND: Peer review, especially prospective peer review, has been supported
      by professional organizations as an important element in optimal Radiation
      Oncology practice based on its demonstration of efficacy at detecting and
      preventing errors prior to patient treatment. Implementation of peer review is
      not without barriers, but solutions do exist to mitigate or eliminate some of
      those barriers. METHODS: Peer review practice at our institution involves three
      key elements: new patient conference, treatment planning conference, and chart
      rounds. The treatment planning conference is an adaptation of the group consensus
      peer review model from radiology which utilizes a group of peers reviewing each
      treatment plan prior to implementation. The peer group in radiation oncology
      includes Radiation Oncologists, Physician Residents, Medical Physicists,
      Dosimetrists, and Therapists. Thus, technical and clinical aspects of each plan
      are evaluated simultaneously. RESULTS: Though peer review is held in high regard
      in Radiation Oncology, many barriers commonly exist preventing optimal
      implementation such as time intensiveness, repetition, and distraction from
      clinic time with patients. Through the use of automated review tools and
      commitment by individuals and administration in regards to staffing, scheduling,
      and responsibilities, these barriers have been mitigated to implement this Group
      Consensus Peer Review model into a Radiation Oncology Clinic. CONCLUSION: A Group
      Consensus Peer Review model has been implemented with strategies to address
      common barriers to effective and efficient peer review.

PMID- 29587868
TI  - Problems recruiting and retaining postnatal women to a pilot randomised
      controlled trial of a web-delivered weight loss intervention.
AB  - OBJECTIVE: This paper highlights recruitment and retention problems identified
      during a pilot randomised controlled trial and process evaluation. The pilot
      trial aimed to evaluate the feasibility and acceptability of a web-delivered
      weight loss intervention for postnatal women and associated trial protocol.
      RESULTS: General practice database searches revealed low rates of eligible
      postnatal women per practice. 16 (10%) of the 168 identified women were recruited
      and randomised, seven to the intervention and nine to the control. 57% (4/7) of
      the intervention women completed 3 month follow-up measurements in comparison to
      56% (5/9) in the control group. By 12 months, retention in the intervention group
      was 43% (3/7), with 2/7 women active on the website, in comparison to 44% (4/9)
      of the control group. Interview findings revealed the web as an acceptable method
      for delivery of the intervention, with the suggestion of an addition of a mobile
      application. Alternative recruitment strategies, using health visitor
      appointments, midwifery departments or mother and baby/toddler groups, should be
      explored. Greater involvement of potential users should enable better recruitment
      methods to be developed. Trial registration ISRCTN: ISRCTN48086713, Registered 26
      October 2012.

PMID- 29587869
TI  - Perspectives of health professionals on the best care settings for pediatric
      trauma casualties: a qualitative study.
AB  - BACKGROUND: Critically-injured children are frequently treated by providers who
      lack specialty pediatric training in facilities that have not been modified for
      the care of children. We set out to understand the attitudes and perspectives of
      policy makers, and senior nursing and medical managers in the Israeli healthcare
      system, concerning the provision of medical care to pediatric trauma casualties
      in emergency departments. METHODS: We conducted semi-structured interviews with
      17 health professionals from medical centers across Israel and the Ministry of
      Health. The interviews were analyzed by qualitative methods. RESULTS: There was
      lack of clarity and uniformity concerning the definition of a pediatric trauma
      casualty. All of the participants attributed extreme importance to the
      professional level of the care team manager, and most suggested that this should
      be a pediatric emergency medicine specialist. They emphasized the importance of
      around-the-clock availability of pediatric medical teams to care for young trauma
      casualties, and the crucial need for caregivers to be equipped with a wide
      variety of professional skills for the adequate treatment of a broad spectrum of
      injuries. All participants described significant variability in pediatric-care
      training and experience among physicians and nurses working in emergency
      departments. Most participants believe that pediatric trauma casualties should be
      treated in designated pediatric emergency departments, in a limited number of
      medical centers across the country. CONCLUSIONS: Our findings indicate that
      specialized pediatric EDs would constitute the best location for intake of
      children with major traumatic injuries. Pediatric emergency medicine specialists
      should manage trauma cases using pediatric surgeons as ad-hoc consultants. The
      term 'pediatric patient' should be defined to allow trauma patients to be
      referred to the most appropriate ED. Teams working at these EDs should undergo
      specialized pediatric emergency medicine training. Finally, to regulate the key
      aspects of trauma care, clear statutory guidelines should be formulated at
      national and local levels.

PMID- 29587870
TI  - Supraspinatus tendon repair using anchors: a biomechanical evaluation in the
      rabbit.
AB  - BACKGROUND: Arthroscopic rotator cuff repairs are mostly secured with suture
      anchors and often supplemented by footprint decortication. The objectives of this
      study were to characterize the strength of bone-tendon healing following anchor
      repair and assess the effect of channeling the supraspinatus (SSP) humeral
      footprint 1 week ahead of reattachment surgery. METHODS: One hundred twelve
      rabbits underwent unilateral detachment of one SSP tendon and were randomly
      assigned to two groups: channeling the footprint at time of detachment and no
      channeling. One week later, reattachment was performed using an anchor. The
      repaired and contralateral shoulders were harvested at 0, 1, 2, or 4 weeks after
      repair and mechanically tested to failure. Outcome measures included load at
      failure, stiffness, and site of failure. RESULTS: Anchor fixation had a mean load
      at failure of 81 +/- 32 N and a stiffness of 27 +/- 9 N/mm immediately after
      repair compared to 166 +/- 47 N and 66 +/- 13 N/mm in the contralateral (both p <
      0.05). Mechanical recovery of the reattached SSP tendon was achieved after 4
      weeks (221 +/- 73 N, 206 +/- 59 N, and 198 +/- 49 N in the channeling, no
      channeling, and contralateral groups, respectively, p > 0.05). The dominant site
      of failure shifted from the footprint at 0/1 week to bone avulsion/mid-substance
      tear at 4 weeks (p < 0.05). There were no differences in outcomes between the
      channeling and no channeling groups. CONCLUSIONS: This study is the first of its
      kind to provide quantitative data on the mechanical properties of the enthesis
      following anchor repair in a rabbit model. Anchor repair led to rapid and
      complete restoration of SSP mechanical properties. Further evidence is needed
      before recommending channeling ahead of repair surgery.

PMID- 29587871
TI  - Amyloid-beta modulates microglial responses by binding to the triggering receptor
      expressed on myeloid cells 2 (TREM2).
AB  - BACKGROUND: TREM2 is an innate immune receptor specifically expressed in
      microglia. Coding variations in TREM2 have been reported to increase the risk for
      Alzheimer's disease (AD) and other neurodegenerative diseases. While multiple
      studies support a role for TREM2 in microglial recruitment to amyloid plaques,
      the chemoattractant factor modulating TREM2-dependent microglial responses has
      not been defined. METHODS: Potential binding of oligomeric amyloid-beta 1-42
      (oAbeta1-42) to TREM2 was tested by complementary approaches including solid
      phase binding, surface plasmon resonance and immunoprecipitation assays. The
      ability of oAbeta1-42 to activate TREM2 signaling pathways was examined by
      analyzing the phosphorylation of Syk and Akt in primary microglia as well as
      TREM2-mediated signaling in a reporter cell system. Lastly, the functional
      outcome of oAbeta1-42-TREM2 interaction was tested by examining impacts on
      microglial migration in vitro and clustering around oAbeta1-42-bearing brain
      areas in vivo. RESULTS: We found that oAbeta1-42 bound to TREM2 with high
      affinity and activated TREM2-dependent signaling pathway. Neither monomeric nor
      scrambled Abeta bound to TREM2 supporting a specific interaction between oAbeta
      and TREM2. The disease-associated mutations of TREM2 reduced its binding affinity
      to oAbeta1-42. Furthermore, we identified several positively charged amino acids
      within residues 31-91 of TREM2 that were crucial for its interaction with oAbeta1
      42. Importantly, oAbeta1-42 promoted microglial migration in vitro and clustering
      in vivo in a TREM2-dependent manner. CONCLUSIONS: Our data establish a critical
      link between oAbeta1-42, a major pathological component of AD, and TREM2, a
      strong genetic risk factor for AD expressed in microglia, and suggest that such
      interaction contributes to the pathogenic events in AD by modulating microglial
      responses.

PMID- 29587872
TI  - Sequencing the exons of human glucocorticoid receptor (NR3C1) gene in Han Chinese
      with high-altitude pulmonary edema.
AB  - BACKGROUND: High-altitude pulmonary edema (HAPE) is a serious acute mountain
      sickness that mainly occurs in non-acclimatized individuals after rapid ascent to
      high altitude. The precise etiology of HAPE remains unclear. This study aimed to
      investigate whether NR3C1 gene polymorphism is associated with the susceptibility
      to HAPE. METHODS: The exons of NR3C1 gene were sequenced by a ABI 3730 DNA
      analyzer in 133 HAPE patients and matched 135 healthy Han Chinese controls from
      the Yushu area in Qinghai (the altitude greater than 3500 m). RESULTS: DNA
      sequencing showed the heterozygous substitutions at codon 588 (rs6194) in exon 6
      and 766 (rs6196) in exon 9 of NR3C1 gene. The genotypic distributions and allelic
      frequencies of NR3C1 SNP rs6194 showed significant differences in two groups (P <
      0.05). The frequencies of the C allele were significantly higher in the HAPE
      group than in the control group (P < 0.05) with an odds ratio of 3.009 (95% CI =
      1.250-7.244). There were no differences in genotypic and allelic frequencies in
      rs6196 polymorphism between the two groups. CONCLUSIONS: NR3C1 gene rs6194
      polymorphism is correlated with HAPE susceptibility. CC genotype and C allele of
      rs6194 polymorphism might increase the risk of HAPE in Han Chinese.

PMID- 29587874
TI  - The effects of different forms of daily exercise on metabolic function following
      short-term overfeeding and reduced physical activity in healthy young men: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Short-term overfeeding combined with reduced physical activity
      impairs metabolic function and alters the expression of key genes within adipose
      tissue. We have shown that daily vigorous-intensity running can prevent these
      changes independent of any net effect on energy imbalance. However, which type,
      intensity and/or duration of exercise best achieves these benefits remains to be
      ascertained. METHODS/DESIGN: Forty-eight healthy young men will be recruited and
      randomly allocated to one of four experimental conditions for 1 week: (1) to
      ingest 50% more energy than normal by over-consuming their habitual diet whilst
      simultaneously restricting their physical activity below 4000 steps day-1 (i.e.
      energy surplus; SUR group); (2) the same regimen but with a daily 45-min bout of
      vigorous-intensity arm crank ergometry at 70% of maximum oxygen uptake (SUR + ARM
      group); (3) the same regimen but with a daily 45-min bout of moderate-intensity
      treadmill walking at 50% of maximum oxygen uptake (SUR + MOD group); (4) the same
      regimen but with the addition of intermittent short bouts of walking during
      waking hours (SUR + BREAKS group). Critically, all exercise groups will receive
      additional dietary energy intake to account for the energy expended by exercise,
      thus maintaining a matched energy surplus. At baseline and follow-up, fasted
      blood samples, abdominal subcutaneous adipose tissue and skeletal muscle biopsies
      will be obtained and oral glucose tolerance tests conducted. DISCUSSION: This
      study will establish the impact of different forms of daily exercise on metabolic
      function at the whole-body level as well as within adipose tissue and skeletal
      muscle in the context of a standardised energy surplus. TRIAL REGISTRATION:
      ISRCTN, ISRCTN18311163 . Registered on 24 June 2015.

PMID- 29587873
TI  - Population genetics analysis of Phlebotomus papatasi sand flies from Egypt and
      Jordan based on mitochondrial cytochrome b haplotypes.
AB  - BACKGROUND: Phlebotomus papatasi sand flies are major vectors of Leishmania major
      and phlebovirus infection in North Africa and across the Middle East to the
      Indian subcontinent. Population genetics is a valuable tool in understanding the
      level of genetic variability present in vector populations, vector competence,
      and the development of novel control strategies. This study investigated the
      genetic differentiation between P. papatasi populations in Egypt and Jordan that
      inhabit distinct ecotopes and compared this structure to P. papatasi populations
      from a broader geographical range. METHODS: A 461 base pair (bp) fragment from
      the mtDNA cytochrome b (cyt b) gene was PCR amplified and sequenced from 116
      individual female sand flies from Aswan and North Sinai, Egypt, as well as
      Swaimeh and Malka, Jordan. Haplotypes were identified and used to generate a
      median-joining network, F ST values and isolation-by-distance were also
      evaluated. Additional sand fly individuals from Afghanistan, Iran, Israel,
      Jordan, Libya, Tunisia and Turkey were included as well as previously published
      haplotypes to provide a geographically broad genetic variation analysis. RESULTS:
      Thirteen haplotypes displaying nine variant sites were identified from P.
      papatasi collected in Egypt and Jordan. No private haplotypes were identified
      from samples in North Sinai, Egypt, two were observed in Aswan, Egypt, four from
      Swaimeh, Jordan and two in Malka, Jordan. The Jordan populations clustered
      separately from the Egypt populations and produced more private haplotypes than
      those from Egypt. Pairwise F ST values fall in the range 0.024-0.648. CONCLUSION:
      The clustering patterns and pairwise F ST values indicate a strong
      differentiation between Egyptian and Jordanian populations, although this
      population structure is not due to isolation-by-distance. Other factors, such as
      environmental influences and the genetic variability in the circulating Le. major
      parasites, could possibly contribute to this heterogeneity. The present study
      aligns with previous reports in that pockets of genetic differentiation exists
      between populations of this widely dispersed species but, overall, the species
      remains relatively homogeneous.

PMID- 29587875
TI  - Evaluation of a novel device for the management of high blood pressure and shock
      in pregnancy in low-resource settings: study protocol for a stepped-wedge cluster
      randomised controlled trial (CRADLE-3 trial).
AB  - BACKGROUND: Obstetric haemorrhage, sepsis and pregnancy hypertension account for
      more than 50% of maternal deaths worldwide. Early detection and effective
      management of these conditions relies on vital signs. The Microlife(r) CRADLE
      Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood
      pressure and pulse. It incorporates a traffic-light early warning system that
      alerts all levels of healthcare provider to the need for escalation of care in
      women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby
      aiding early recognition of haemodynamic instability and preventing maternal
      mortality and morbidity. The aim of the trial was to determine whether
      implementation of the CRADLE intervention (the Microlife(r) CRADLE VSA device and
      CRADLE training package) into routine maternity care in place of existing
      equipment will reduce a composite outcome of maternal mortality and morbidity in
      low- and middle-income country populations. METHODS: The CRADLE-3 trial was a
      stepped-wedge cluster-randomised controlled trial of the CRADLE intervention
      compared to routine maternity care. Each cluster crossed from routine maternity
      care to the intervention at 2-monthly intervals over the course of 20 months
      (April 2016 to November 2017). All women identified as pregnant or within 6 weeks
      postpartum, presenting for maternity care in cluster catchment areas were
      eligible to participate. Primary outcome data (composite of maternal death,
      eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10
      clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia;
      Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti;
      South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the
      Medical Research Council guidance for complex interventions. A process evaluation
      was undertaken to evaluate implementation in each site and a cost-effectiveness
      evaluation will be undertaken. DISCUSSION: All aspects of this protocol have been
      evaluated in a feasibility study, with subsequent optimisation of the
      intervention. This trial will demonstrate the potential impact of the CRADLE
      intervention on reducing maternal mortality and morbidity in low-resource
      settings. It is anticipated that the relatively low cost of the intervention and
      ease of integration into existing health systems will be of significant interest
      to local, national and international health policy-makers. TRIAL REGISTRATION:
      ISCRTN41244132. Registered on 2 February 2016. Prospective protocol modifications
      have been recorded and were communicated to the Ethics Committees and Trials
      Committees. The adapted Standard Protocol Items: Recommendations for
      Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as
      Additional file 1.

PMID- 29587876
TI  - Native entomopathogenic Metarhizium spp. from Burkina Faso and their virulence
      against the malaria vector Anopheles coluzzii and non-target insects.
AB  - BACKGROUND: Genetically enhanced Metarhizium pingshaense are being developed for
      malaria vector control in Burkina Faso. However, not much is known about the
      local prevalence and pathogenicity of this fungus, so we prospected mosquitoes
      and plant roots (a common habitat for Metarhizium spp.) for entomopathogenic
      fungi. RESULTS: Our investigations showed that Metarhizium spp. represented
      between 29-74% of fungi isolated from plant root rhizospheres in diverse
      collection sites. At low spore dosages (1 * 106 conidia/ml), two mosquito-derived
      M. pingshaense isolates (Met_S26 and Met_S10) showed greater virulence against
      Anopheles coluzzii (LT80 of ~7 days) than isolates tested in previous studies
      (LT80 of ~10 days). In addition, the local isolates did not cause disease in non
      target insects (honeybees and cockroaches). CONCLUSIONS: Our work provides
      promising findings for isolating local Metarhizium strains for application in
      mosquito biological control and for future transgenic biocontrol strategies in
      Burkina Faso.

PMID- 29587877
TI  - Occurrence and distribution of Giardia species in wild rodents in Germany.
AB  - BACKGROUND: Giardiasis is an important gastrointestinal parasitic disease in
      humans and other mammals caused by the protozoan Giardia duodenalis. This species
      complex is represented by genetically distinct groups (assemblages A-H) with
      varying zoonotic potential and host preferences. Wild rodents can harbor
      potentially zoonotic assemblages A and B, and the rodent-specific assemblage G.
      Other Giardia spp. found in these animals are Giardia muris and Giardia microti.
      For the latter, only limited information on genetic typing is available. It has
      been speculated that wild rodents might represent an important reservoir for
      parasites causing human giardiasis. The aim of this study was to investigate the
      occurrence and distribution of Giardia spp. and assemblage types in wild rodents
      from different study sites in Germany. RESULTS: Screening of 577 wild rodents of
      the genera Apodemus, Microtus and Myodes, sampled at eleven study sites in
      Germany, revealed a high overall Giardia prevalence. Giardia species
      determination at the SSU rDNA gene locus revealed that Apodemus mice, depending
      on species, were predominantly infected with one of two distinct G. muris
      sequence types. Giardia microti was the predominant parasite species found in
      voles of the genera Microtus and Myodes. Only a few animals were positive for
      potentially zoonotic G. duodenalis. Subtyping at the beta-giardin (bg) and
      glutamine dehydrogenase (gdh) genes strongly supported the existence of different
      phylogenetic subgroups of G. microti that are preferentially harbored by distinct
      host species. CONCLUSIONS: The present study highlights the preference of G.
      muris for Apodemus, and G. microti for Microtus and Myodes hosts and argues for a
      very low prevalence of zoonotic G. duodenalis assemblages in wild rodents in
      Germany. It also provides evidence that G. muris and G. microti subdivide into
      several phylogenetically distinguishable subgroups, each of which appears to be
      preferentially harbored by species of a particular rodent host genus. Finally,
      the study expands the database of sequences relevant for sequence typing of G.
      muris and G. microti isolates which will greatly help future analyses of these
      parasites' population structure.

PMID- 29587878
TI  - Is Afamin a novel biomarker for gestational diabetes mellitus? A pilot study.
AB  - BACKGROUND: In search of potential early biomarkers for timely prediction of
      gestational diabetes mellitus (GDM), we focused on afamin, a vitamin E-binding
      protein in human plasma.. Afamin plays a role in anti-apoptotic cellular
      processes related to oxidative stress and is associated with insulin resistance
      and other features of metabolic syndrome. During uncomplicated pregnancy its
      serum concentrations increase linearly. The aim of this study was to investigate
      the suitability of afamin as early marker for predicting GDM. METHODS: In a first
      trimester cohort from a prospective observational study of adverse pregnancy
      outcomes we secondarily analyzed afamin concentrations in 59 patients diagnosed
      with GDM and 51 controls. Additionally, afamin concentrations were cross
      sectionally examined in a mid-trimester cohort of 105 women and compared with
      results from a simultaneously performed oral glucose tolerance test (OGTT).
      Subgroup analysis comparing patients treated with either insulin (iGDM) or
      dietary intervention (dGDM) was performed in both cohorts. Patients were
      recruited at the University Hospital Essen, Germany, between 2003 and 2016.
      RESULTS: Results were adjusted for body-mass-index (BMI) and gestational age.
      First and mid-trimester cohorts yielded significantly elevated afamin
      concentrations in patients with pathological OGTT compared to patients without
      GDM (first trimester cohort: mean, 113.4 mg/l; 95% CI, 106.4-120.5 mg/l and 87.2
      mg/l; 95% CI, 79.7-94.7 mg/l; mid-trimester cohort: mean, 182.9 mg/l; 95% CI,
      169.6-196.2 mg/l and 157.3 mg/l; 95% CI, 149.1-165.4 mg/l, respectively). In the
      first-trimester cohort, patients developing iGDM later in pregnancy presented
      with significantly higher afamin concentrations compared to patients developing
      dGDM and compared to patients without GDM. In the mid-trimester cohort, mean
      concentrations of afamin differed significantly between patients with dGDM
      compared to controls and between patients with iGDM and controls. Patients with
      iGDM showed only slightly higher afamin levels compared to patients with dGDM.
      CONCLUSION: Afamin may serve as a new early biomarker for pathological glucose
      metabolism during pregnancy. Further research is needed to determine afamin's
      concentrations during pregnancy, its predictive value for early detection of
      pregnancies at high risk to develop GDM and its diagnostic role during the second
      trimester.

PMID- 29587879
TI  - Rituximab impedes natural killer cell function in Chronic Fatigue
      Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation.
AB  - BACKGROUND: A recent in vitro pilot investigation reported Rituximab
      significantly reduced natural killer (NK) cell cytotoxicity in healthy donors.
      Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating
      disorder of unknown etiology. A consistent finding is a significant reduction in
      NK cell cytotoxicity. Rituximab has been reported having questionable potential
      therapeutic benefits for the treatment of CFS/ME, however, the potential effects
      of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined.
      METHODS: A total of eight CFS/ME patients (48.63 +/- 15.69 years) and nine non
      fatigued controls (NFC) (37.56 +/- 11.06 years) were included using the Fukuda
      case definition. Apoptotic function, lytic proteins and degranulation markers
      were measured on isolated NK cells using flow cytometry following overnight
      incubation with Rituximab at 10 MUg/ml and 100 MUg/ml. RESULTS: There was a
      significant reduction in NK cell lysis between CFS/ME patients and NFC following
      incubation with Rituximab at 100 MUg/ml at 12.5:1 and 6.25:1 effecter-target
      (E:T) ratios (p < 0.05). However, there was no significant difference for NFC
      following incubation with Rituximab at 10 MUg/ml and 100 MUg/ml. There was no
      significant difference between CFS/ME patients and NFC for granzyme A and
      granzyme B prior to incubation with Rituximab and following overnight incubation
      with Rituximab at 10 MUg/ml. There was a significant decrease in granzyme B in
      CFS/ME patients compared to NFC with 100 MUg/ml of Rituximab prior to K562 cells
      stimulation (p < 0.05). There was a significant increase in CD107a (p < 0.05) and
      CD107b expression (p < 0.01) in NFC after stimulation with K562 cells prior to
      incubation with Rituximab. There was a significant increase in CD107b expression
      between CFS/ME patients and NFC prior to incubation with Rituximab and without
      stimulation of K562 cells (p < 0.01). Importantly, there was a significant
      increase in CD107b following overnight incubation with 100 MUg/ml of Rituximab in
      NFC prior to K562 cells stimulation (p < 0.01). CONCLUSION: This study reports
      significant decreases in NK cell lysis and a significant increase in NK cell
      degranulation following Rituximab incubation in vitro in CFS/ME patients,
      suggesting Rituximab may be toxic for NK cells. Caution should be observed in
      clinical trials until further investigations in a safe and controlled in vitro
      setting are completed.

PMID- 29587880
TI  - Hybridization capture reveals microbial diversity missed using current profiling
      methods.
AB  - BACKGROUND: Microorganisms comprise the majority of living organisms on our
      planet. For many years, exploration of the composition of microbial communities
      has been performed through the PCR-based study of the small subunit rRNA gene due
      to its high conservation across the domains of life. The application of this
      method has resulted in the discovery of many unexpected evolutionary lineages.
      However, amplicon sequencing is subject to numerous biases, with some taxa being
      missed, and is limited by the read length of second-generation sequencing
      platforms, which drastically reduces the phylogenetic resolution. RESULTS: Here,
      we describe a hybridization capture strategy that allows the enrichment of 16S
      rRNA genes from metagenomic samples and enables an exhaustive identification and
      a complete reconstruction of the biomarker. Applying this approach to a microbial
      mock community and a soil sample, we demonstrated that hybridization capture is
      able to reveal greater microbial diversity than 16S rDNA amplicon sequencing and
      shotgun sequencing. The reconstruction of full-length 16S rRNA genes facilitated
      the improvement of phylogenetic resolution and the discovery of novel prokaryotic
      taxa. CONCLUSIONS: Our results demonstrate that hybridization capture can lead to
      major breakthroughs in our understanding of microbial diversity, overcoming the
      limitations of conventional 16S rRNA gene studies. If applied to a broad range of
      environmental samples, this innovative approach could reveal the undescribed
      diversity of the still underexplored microbial communities and could provide a
      better understanding of ecosystem function.

PMID- 29587881
TI  - TEDDI: radiotherapy delivery in deep inspiration for pediatric patients - a NOPHO
      feasibility study.
AB  - BACKGROUND: Radiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is
      a simple technique, in which changes in patient anatomy can significantly reduce
      the irradiation of the organs at risk (OARs) surrounding the treatment target.
      DIBH is routinely used in the treatment of some adult patients to diminish the
      risk of late effects; however, no formalized studies have addressed the potential
      benefit of DIBH in children. METHODS/DESIGN: TEDDI is a multicenter, non
      randomized, feasibility study. The study investigates the dosimetric benefit of
      RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also,
      the study aims to establish the compliance to DIBH and to determine the accuracy
      and reproducibility in a pediatric setting. Pediatric patients (aged 5-17 years)
      with a tumor in the mediastinum or upper abdomen with the possible need of RT
      will be included in the study. Written informed consent is obligatory. Prior to
      any treatment, patients will undergo a DIBH training session followed by a
      diagnostic PET/CT- or CT-staging scan in both DIBH and FB. If the patient
      proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and
      two separate treatment plans will be calculated. The superior treatment plan,
      i.e. equal target coverage and lowest overall dose to the OARs, will be chosen
      for treatment. Patient comfort will be assessed daily by questionnaires and by
      adherence to the respiratory management procedure. DISCUSSION: RT in DIBH is
      expected to diminish irradiation of the OARs surrounding the treatment target and
      thereby reduce the risk of late effects in childhood cancer survivors. TRIAL
      REGISTRATION: The Danish Ethical Committee (H-16035870, approved November 24th
      2016, prospectively registered). The Danish Data Protection Agency (2012-58-0004,
      approved January 1st 2017, prospectively registered). Registered at
      clinicaltrials.gov ( NCT03315546 , October 20th  2017, retrospectively
      registered).

PMID- 29587882
TI  - Comparative effectiveness of malaria prevention measures: a systematic review and
      network meta-analysis.
AB  - BACKGROUND: Malaria causes significant morbidity and mortality worldwide. There
      are several preventive measures that are currently employed, including
      insecticide-treated nets (ITNs, including long-lasting insecticidal nets and
      insecticidal-treated bed nets), indoor residual spraying (IRS), prophylactic
      drugs (PD), and untreated nets (UN). However, it is unclear which measure is the
      most effective for malaria prevention. We therefore undertook a network meta
      analysis to compare the efficacy of different preventive measures on incidence of
      malaria infection. METHODS: A systematic literature review was undertaken across
      four medical and life sciences databases (PubMed, Cochrane Central, Embase, and
      Web of Science) from their inception to July 2016 to compare the effectiveness of
      different preventive measures on malaria incidence. Data from the included
      studies were analysed for the effectiveness of several measures against no
      intervention (NI). This was carried out using an automated generalized pairwise
      modeling (GPM) framework for network meta-analysis to generate mixed treatment
      effects against a common comparator of no intervention (NI). RESULTS: There were
      30 studies that met the inclusion criteria from 1998-2016. The GPM framework led
      to a final ranking of effectiveness of measures in the following order from best
      to worst: PD, ITN, IRS and UN, in comparison with NI. However, only ITN (RR:
      0.49, 95% CI: 0.32-0.74) showed precision while other methods [PD (RR: 0.24, 95%
      CI: 0.004-15.43), IRS (RR: 0.55, 95% CI: 0.20-1.56) and UN (RR: 0.73, 95% CI:
      0.28-1.90)] demonstrating considerable uncertainty associated with their point
      estimates. CONCLUSION: Current evidence is strong for the protective effect of
      ITN interventions in malaria prevention. Even though ITNs were found to be the
      only preventive measure with statistical support for their effectiveness, the
      role of other malaria control measures may be important adjuncts in the global
      drive to eliminate malaria.

PMID- 29587886
TI  - A definition of free sugars for the UK.
AB  - Public Health England has set a definition for free sugars in the UK in order to
      estimate intakes of free sugars in the National Diet and Nutrition Survey. This
      follows the recommendation from the Scientific Advisory Committee on Nutrition in
      its 2015 report on Carbohydrates and Health that a definition of free sugars
      should be adopted. The definition of free sugars includes: all added sugars in
      any form; all sugars naturally present in fruit and vegetable juices, purees and
      pastes and similar products in which the structure has been broken down; all
      sugars in drinks (except for dairy-based drinks); and lactose and galactose added
      as ingredients. The sugars naturally present in milk and dairy products, fresh
      and most types of processed fruit and vegetables and in cereal grains, nuts and
      seeds are excluded from the definition.

PMID- 29587884
TI  - Effectiveness of psychological interventions to improve quality of life in people
      with long-term conditions: rapid systematic review of randomised controlled
      trials.
AB  - BACKGROUND: Long-term conditions may negatively impact multiple aspects of
      quality of life including physical functioning and mental wellbeing. The rapid
      systematic review aimed to examine the effectiveness of psychological
      interventions to improve quality of life in people with long-term conditions to
      inform future healthcare provision and research. METHODS: EBSCOhost and OVID were
      used to search four databases (PsychInfo, PBSC, Medline and Embase). Relevant
      papers were systematically extracted by one researcher using the predefined
      inclusion/exclusion criteria based on titles, abstracts, and full texts.
      Randomized controlled trial psychological interventions conducted between 2006
      and February 2016 to directly target and assess people with long-term conditions
      in order to improve quality of life were included. Interventions without long
      term condition populations, psychological intervention and/or patient-assessed
      quality of life were excluded. RESULTS: From 2223 citations identified, 6
      satisfied the inclusion/exclusion criteria. All 6 studies significantly improved
      at least one quality of life outcome immediately post-intervention. Significant
      quality of life improvements were maintained at 12-months follow-up in one out of
      two studies for each of the short- (0-3 months), medium- (3-12 months), and long
      term (>= 12 months) study duration categories. CONCLUSIONS: All 6 psychological
      intervention studies significantly improved at least one quality of life outcome
      immediately post-intervention, with three out of six studies maintaining effects
      up to 12-months post-intervention. Future studies should seek to assess the
      efficacy of tailored psychological interventions using different formats,
      durations and facilitators to supplement healthcare provision and practice.

PMID- 29587887
TI  - Excess free fructose, high-fructose corn syrup and adult asthma: the Framingham
      Offspring Cohort.
AB  - There is growing evidence that intakes of high-fructose corn syrup (HFCS), HFCS
      sweetened soda, fruit drinks and apple juice - a high-fructose 100 % juice - are
      associated with asthma, possibly because of the high fructose:glucose ratios and
      underlying fructose malabsorption, which may contribute to enteral formation of
      pro-inflammatory advanced glycation end products, which bind receptors that are
      mediators of asthma. Cox proportional hazards models were used to assess
      associations between intakes of these beverages and asthma risk, with data from
      the Framingham Offspring Cohort. Diet soda and orange juice - a 100 % juice with
      a 1:1 fructose:glucose ratio - were included for comparison. Increasing intake of
      any combination of HFCS-sweetened soda, fruit drinks and apple juice was
      significantly associated with progressively higher asthma risk, plateauing at 5-7
      times/week v. never/seldom, independent of potential confounders (hazard ratio
      1.91, P<0.001). About once a day consumers of HFCS-sweetened soda had a 49 %
      higher risk (P<0.011), moderate apple juice consumers (2-4 times/week) had a 61 %
      higher risk (P<0.007) and moderate fruit drink consumers had a 58 % higher risk
      (P<0.009), as compared with never/seldom consumers. There were no associations
      with diet soda/orange juice. These associations are possibly because of the high
      fructose:glucose ratios, and fructose malabsorption. Recommendations to reduce
      consumption may be inadequate to address asthma risk, as associations are evident
      even with moderate intake of these beverages, including apple juice - a 100 %
      juice. The juice reductions in the US Special Supplemental Nutrition Program for
      Women, Infants, and Children in 2009, and the plateauing/decreasing asthma
      prevalence (2010-2013), particularly among non-Hispanic black children, may be
      related. Further research regarding the consequences of fructose malabsorption is
      needed.

PMID- 29587888
TI  - Depression and hopelessness as risk factors for suicide ideation, attempts and
      death: meta-analysis of longitudinal studies.
AB  - BACKGROUND: Many studies have documented robust relationships between depression
      and hopelessness and subsequent suicidal thoughts and behaviours; however, much
      weaker and non-significant effects have also been reported. These inconsistencies
      raise questions about whether and to what degree these factors confer risk for
      suicidal thoughts and behaviours.AimsThis study aimed to evaluate the magnitude
      and clinical utility of depression and hopelessness as risk factors for suicide
      ideation, attempts and death. METHOD: We conducted a meta-analysis of published
      studies from 1971 to 31 December 2014 that included at least one longitudinal
      analysis predicting suicide ideation, attempt or death using any depression or
      hopelessness variable. RESULTS: Overall prediction was weaker than anticipated,
      with weighted mean odds ratios of 1.96 (1.81-2.13) for ideation, 1.63 (1.55-1.72)
      for attempt and 1.33 (1.18-1.49) for death. Adjusting for publication bias
      further reduced estimates. Effects generally persisted regardless of sample
      severity, sample age or follow-up length. CONCLUSIONS: Several methodological
      constraints were prominent across studies; addressing these issues would likely
      be fruitful moving forward.Declaration of interestNone.

PMID- 29587889
TI  - A psychosocial assessment and management tool for children and youth in crisis.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Emergency clinicians are not
      specifically trained to assess and manage mental health emergencies; thus, they
      have wide practice variation while determining disposition for children with
      mental health crises.What did this study ask?What is the inter-user reliability
      of a new emergency psychosocial assessment and management guiding tool,
      HEARTSMAP, and the impact of implementing it in a pediatric emergency
      department?What did this study find?The tool demonstrated strong inter-rater
      reliability between PED clinicians and was associated with high rates of
      outpatient resource connectivity.Why does this study matter to
      clinicians?HEARTSMAP can provide emergency clinicians with reliable and
      comprehensive assessment and management strategies for youth presenting with
      mental health-related concerns.

PMID- 29587883
TI  - Elevated polygenic burden for autism is associated with differential DNA
      methylation at birth.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a severe neurodevelopmental
      disorder characterized by deficits in social communication and restricted,
      repetitive behaviors, interests, or activities. The etiology of ASD involves both
      inherited and environmental risk factors, with epigenetic processes hypothesized
      as one mechanism by which both genetic and non-genetic variation influence gene
      regulation and pathogenesis. The aim of this study was to identify DNA
      methylation biomarkers of ASD detectable at birth. METHODS: We quantified
      neonatal methylomic variation in 1263 infants-of whom ~ 50% went on to
      subsequently develop ASD-using DNA isolated from archived blood spots taken
      shortly after birth. We used matched genotype data from the same individuals to
      examine the molecular consequences of ASD-associated genetic risk variants,
      identifying methylomic variation associated with elevated polygenic burden for
      ASD. In addition, we performed DNA methylation quantitative trait loci (mQTL)
      mapping to prioritize target genes from ASD GWAS findings. RESULTS: We identified
      robust epigenetic signatures of gestational age and prenatal tobacco exposure,
      confirming the utility of DNA methylation data generated from neonatal blood
      spots. Although we did not identify specific loci showing robust differences in
      neonatal DNA methylation associated with later ASD, there was a significant
      association between increased polygenic burden for autism and methylomic
      variation at specific loci. Each unit of elevated ASD polygenic risk score was
      associated with a mean increase in DNA methylation of - 0.14% at two CpG sites
      located proximal to a robust GWAS signal for ASD on chromosome 8. CONCLUSIONS:
      This study is the largest analysis of DNA methylation in ASD undertaken and the
      first to integrate genetic and epigenetic variation at birth. We demonstrate the
      utility of using a polygenic risk score to identify molecular variation
      associated with disease, and of using mQTL to refine the functional and
      regulatory variation associated with ASD risk variants.

PMID- 29587890
TI  - Determining the Attributable Costs of Clostridium difficile Infections When
      Exposure Time Is Lacking: Be Wary of "Conditioning on the Future".

PMID- 29587891
TI  - Morbidity, mortality and long-term sequelae of West Nile virus disease in Quebec.
AB  - We aimed to describe the clinical characteristics of West Nile patients reported
      in Quebec in 2012 and 2013 and to document physical, mental and functional status
      24 months after symptom onset according to illness severity. The cases were
      recruited by a public health professional. Data were collected from public health
      files, medical records and two standardised phone questionnaires: the Short Form
      36 and the Instrumental Activities of Daily Living. In all, 92 persons
      participated in the study (25 had West Nile fever (WNF), 18 had meningitis and 49
      had encephalitis). Encephalitis participants were older, had more underlying
      medical conditions, more neurological symptoms, worse hospital course and higher
      lethality than meningitis or WNF participants. Nearly half of the surviving
      hospitalised encephalitis patients required extra support upon discharge. At 24
      month follow-up, encephalitis and meningitis patients had a lower score in two
      domains of the mental component: mental health and social functioning (P = 0.0025
      and 0.0297, respectively) compared with the norms based on age- and sex-matched
      Canadians. Physical status was not affected by West Nile virus (WNV) infection.
      In addition, 5/36 (15%) of encephalitis, 1/17 (6%) of meningitis and 1/23 (5%) of
      WNF participants had new functional limitations 24 months after symptom onset. In
      summary, mental and functional sequelae in encephalitis patients are likely to
      represent a source of long-term morbidity. Preventive measures should target
      patients at higher risk of severe illness after WNV infection.

PMID- 29587892
TI  - Equality of care between First Nations and non-First Nations patients in
      Saskatoon emergency departments.
AB  - CLINICIAN'S CAPSULE What is known about the topic? There are concerns regarding
      unequal treatment towards First Nations people when engaged with health care
      services. What did this study ask? Whether quantitative differences in care exist
      between First Nations and non-First Nations patients in the ED. What did this
      study find? First Nations presenting with abdominal pain were found to have no
      difference in the time-related care parameters relative to non-First Nations
      patients. Why does this study matter to clinicians? Future quantitative and
      qualitative studies will be necessary to further understand the care inequality
      that has been expressed among First Nations patients.

PMID- 29587893
TI  - Public Health and Mental Health Implications of Environmentally Induced Forced
      Migration.
AB  - ABSTRACTClimate change is increasingly forcing population displacement, better
      described by the phrase environmentally induced forced migration. Rising global
      temperatures, rising sea levels, increasing frequency and severity of natural
      disasters, and progressive depletion of life-sustaining resources are among the
      drivers that stimulate population mobility. Projections forecast that current
      trends will rapidly accelerate. This will lead to an estimated 200 million
      climate migrants by the year 2050 and create dangerous tipping points for public
      health and security.Among the public health consequences of climate change,
      environmentally induced forced migration is one of the harshest and most harmful
      outcomes, always involving a multiplicity of profound resource and social losses
      and frequently exposing migrants to trauma and violence. Therefore, one
      particular aspect of forced migration, the effects of population displacement on
      mental health and psychosocial functioning, deserves dedicated focus. Multiple
      case examples are provided to elucidate this theme. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 7).

PMID- 29587885
TI  - Microbial interactions within the plant holobiont.
AB  - Since the colonization of land by ancestral plant lineages 450 million years ago,
      plants and their associated microbes have been interacting with each other,
      forming an assemblage of species that is often referred to as a "holobiont."
      Selective pressure acting on holobiont components has likely shaped plant
      associated microbial communities and selected for host-adapted microorganisms
      that impact plant fitness. However, the high microbial densities detected on
      plant tissues, together with the fast generation time of microbes and their more
      ancient origin compared to their host, suggest that microbe-microbe interactions
      are also important selective forces sculpting complex microbial assemblages in
      the phyllosphere, rhizosphere, and plant endosphere compartments. Reductionist
      approaches conducted under laboratory conditions have been critical to decipher
      the strategies used by specific microbes to cooperate and compete within or
      outside plant tissues. Nonetheless, our understanding of these microbial
      interactions in shaping more complex plant-associated microbial communities,
      along with their relevance for host health in a more natural context, remains
      sparse. Using examples obtained from reductionist and community-level approaches,
      we discuss the fundamental role of microbe-microbe interactions (prokaryotes and
      micro-eukaryotes) for microbial community structure and plant health. We provide
      a conceptual framework illustrating that interactions among microbiota members
      are critical for the establishment and the maintenance of host-microbial
      homeostasis.

PMID- 29587894
TI  - Maternal fish consumption during pregnancy and smoking behavioural patterns.
AB  - n-3 Highly unsaturated fatty acids (HUFA), are essential components of neuronal
      membranes and mediate a range of complex bioactive properties including gene
      expression, myelination, cell-signalling and dopaminergic function. Deficits in n
      3 HUFA have been linked to increased risks for addictive disorders, thus we
      posited that lower fish consumption would be associated with greater risks for
      perinatal smoking among 9640 mothers enroled in the Avon Longitudinal Study of
      Parents and Children. We used univariable and multivariable regression models to
      examine relationships between self-reported prenatal dietary intakes of n-3 HUFA
      rich foods (fish and shellfish) and maternal smoking; outcomes included cessation
      and the number of cigarettes smoked per d. Both before and during pregnancy,
      there was consistent evidence (P<0.001) of protective fish intake-smoking
      associations; relative to mothers reporting no fish consumption, those who
      reported some fish consumption (<340 g/week) and high fish consumption (340
      g+/week) at 32 weeks of gestation showed lower likelihoods of smoking (adjusted P
      values <0.001). Respective OR for these relationships were 0.87 (95% CI 0.77,
      0.97) and 0.73 (95% CI 0.61, 0.86). Although the prevalence of smoking
      diminished, from a high of 31.6% (pre-pregnancy) to a low of 18.7% (second
      trimester), the magnitude of fish intake-smoking associations remained stable
      following adjustment for confounders. These observations suggest that greater
      fish or n-3 HUFA consumption should be evaluated as an intervention to reduce or
      prevent smoking in randomised clinical trials.

PMID- 29587895
TI  - Absence of cerebrospinal fluid antineuronal antibodies in schizophrenia spectrum
      disorders.
AB  - SummaryAntibody-mediated encephalitis has been discussed as one possible cause
      for isolated psychotic syndromes. Mostly based on serum samples, findings have
      been controversial. We present the results of a retrospective study of 124
      clinically diagnosed psychotic patients without documented relevant neurological
      symptoms. All were tested for different antineuronal antibodies in cerebrospinal
      fluid (CSF) while 81 received serum testing. Antineuronal antibodies in CSF were
      negative across the sample. 3.7% showed low positive serum antibodies. Our
      findings highlight the importance of a deeper discussion about the relevance of
      low positive serum antibodies without concurrent findings in CSF or clinical
      signs for autoimmune encephalitis.Declaration of interestNone.

PMID- 29587896
TI  - Development and assessment of an improved recombinant multiepitope antigen-based
      immunoassay to diagnose chronic Chagas disease.
AB  - The use of chimeric molecules fusing several antigenic determinants is a
      promising strategy for the development of low-cost, standardized and reliable
      kits to determine specific antibodies. In this study, we designed and assessed a
      novel recombinant chimera that complements the performance of our previously
      developed chimera, CP1 [FRA and SAPA antigens (Ags)], to diagnose chronic Chagas
      disease. The new chimeric protein, named CP3, is composed of MAP, TcD and
      TSSAII/V/VI antigenic determinants. We compared the performance of both chimeric
      Ags using a panel of 67 Trypanosoma cruzi-reactive sera and 67 non-reactive ones.
      The sensitivity of CP3 vs CP1 was 100 and 90.2%, and specificity was 92.5 and
      100%, respectively. The mixture of CP1 + CP3 achieved 100% of sensitivity and
      specificity. More importantly, an additional subset of 17 sera from patients with
      discordant results of conventional serological methods was analysed; the CP1 +
      CP3 mixture allowed us to accurately classify 14 of them with respect to IIF, the
      usual technique used in most of the reference centres. These results show an
      improved performance of the CP1 + CP3 mixture in comparison with enzyme-linked
      immunosorbent assay and indirect haemagglutination commercial assays.

PMID- 29587897
TI  - Antimicrobial Potential of Sicilian Honeys Against Staphylococcus aureus and
      Pseudomonas aeruginosa.
AB  - The purpose of this study was to investigate the antibacterial effect of 71
      organic Sicilian honeys of different botanical origins against Staphylococcus
      aureus [American Type Culture Collection (ATCC) 9144TM] and Pseudomonas
      aeruginosa (ATCC 27853TM). The antimicrobial activity was determined by means of
      an agar diffusion assay from the estimation of the diameter of the inhibition
      zone produced by the honeys. S. aureus was more inhibited than P. aeruginosa (chi
      square value 11.2698, P value 0.000788). In particular, a statistically
      significant inhibition growth against S. aureus was exhibited by the polyfloral
      (chi-square value 6.1714, P value 0.012983) and the eucalyptus honeys (chi-square
      value 4, P value 0.0455). Results partially suggest Sicilian organic polyfloral
      and eucalyptus honeys as possible alternatives to antimicrobial agents when S.
      aureus resistance causes failure of initial conventional antibiotic treatment.

PMID- 29587898
TI  - [Preface].

PMID- 29587899
TI  - [Discussion of the Application of Micro-lecture in the Clinical Training ?of
      Thoracic Surgery].
AB  - Today, with the rapid development of network information technology, the micro
      lecture plays a role in the teaching activities is becoming more and more
      important. The short and efficient teaching content of micro-lecture can be
      downloaded rapidly, expediently, and repeatedly, which improve the learning
      efficiency and independent learning capability. The clinical training of thoracic
      surgery elementarily remains at the scrabble stage. We require continuous reform
      and introduce new modes of teaching, which compatible with the development of
      society and the study habits of novice, to enhance the effectiveness of clinical
      training. In this paper, the concept, characteristic and advantage of micro
      lecture was discussed, and the feasibility of application of micro-lecture in
      thoracic surgery teaching was also discussed. Our aim was to promote the
      application of micro-lecture in the clinical training of thoracic surgery
      reasonable and extensive.?.

PMID- 29587900
TI  - [Application of Thoracic Surgery Structured Electronic Medical Record Based on
      Standard Vocabulary].
AB  - As an important carrier in the information construction of modern hospitals,
      electronic medical record is becoming more and more refined and intelligent. This
      paper introduces the standardized and structured electronic medical record system
      of thoracic surgecal department and puts forward the effect evaluation and
      prospect. ?.

PMID- 29587901
TI  - [Thinking on the Training of Uniportal Video-assisted Thoracic Surgery].
AB  - Recently, uniportal video-assisted thoracic surgery (VATS) has developed rapidly
      and has become the main theme of global surgical development. The specific,
      standardized and systematic training of this technology has become an important
      topic. Specific training in the uniportal VATS approach is crucial to ensure
      safety and radical treatment. Such training approach, including a direct
      interaction with experienced surgeons in high-volume centers, is crucial and
      represents an indispensable step. Another form of training that usually occurs
      after preceptorship is proctorship: an experienced mentor can be invited to a
      trainee's own center to provide specific on-site tutelage. Videos published
      online are commonly used as training material. Technology has allowed the use of
      different models of simulators for training. The most common model is the use of
      animal wet laboratory training. Other models, however, have been used
      mostrecently, such as the use of 3D and VR Technology, virtual reality
      simulators, and completely artificial models of the human thorax with synthetic
      lung, vessel, airway, and nodal tissues. A short-duration, high-volume, clinical
      immersion training, and a long term systematic training in high-volume centers
      are getting more and more attention. According to the evaluation of students'
      grading, a diversified training mode is adopted and the targeted training in
      accordance with different students helps to improve the training effect. We have
      done some work in systematic and standardized training of uniportal VATS in
      single center. We believe such training is feasible and absolutely necessary.

PMID- 29587902
TI  - [Surgical Treatment of Malignant Thymoma Invading the Superior Vena Cava].
AB  - This paper introduced surgical treatment of malignancy-related superior vena cava
      syndrome. Typical cases were presented with diagnostic radiology results. Authors
      focused on the main approach to the malignancy-related superior vena cava
      syndrome of surgery. In order to make it simple for junior doctors to learn and
      practice, all 4 operation methods were described in details. The writer hopes it
      would be helpful for all the young thoracic surgeons.?.

PMID- 29587903
TI  - [Minimally Invasive Surgery in Thymic Malignances].
AB  - Surgery is the most important therapy for thymic malignances. The last decade has
      seen increasing adoption of minimally invasive surgery (MIS) for thymectomy. MIS
      for early stage thymoma patients has been shown to yield similar oncological
      results while being helpful in minimize surgical trauma, improving postoperative
      recovery, and reduce incisional pain. Meanwhile, With the advance in surgical
      techniques, the patients with locally advanced thymic tumors, preoperative
      induction therapies or recurrent diseases, may also benefit from MIS in selected
      cases.

PMID- 29587904
TI  - [Research Status of the Skeletalre Construction of Chest Wall].
AB  - Chest wall defect may be caused by many factors such as the resection of tumor
      and trauma, and the reconstruction of bone-defection is still the key point of
      thoracic surgery. With the development of material science, more and more new
      materials have been used in medical practice, which makes huge progress in the
      surgery of chest wall. However, none of these materials satisfy all the practical
      needs of the reconstruction. Recently, with the development of the capacity of
      computer, 3D-printing technology has been gradually used in clinical work, and
      the idea of individual treatment has been accepted by more and more people. The
      weakness of these materials may be solved by the new material and the application
      of individual treatment, which could also make great advance in chest wall
      surgery. This article will make a summary of the research on the reconstruction
      of chest wall.?.

PMID- 29587905
TI  - [Repair and Reconstruction of Chest Wall Defect].

PMID- 29587906
TI  - [A Comparative Study of Acute and Chronic Pain between Single Port and Triple
      Port Video-assisted Thoracic Surgery for Lung Cancer].
AB  - BACKGROUND: Through the comparative analysis of the acute and chronic pain
      postoperative between the single port and triple port video-assisted thoracic
      surgery to seek the better method which can reduce the incidence of acute and
      chronic pain in patients with lung cancer. METHODS: Data of 232 patients who
      underwent single port -VATS (n=131) or triple port VATS (n=101) for non-small
      cell lung cancer (NSCLC) on January 1, 2016 to June 30, 2017 in our hospital were
      analyzed. The clinical and operative data were assessed, numeric rating scale
      (NRS) was used to evaluate the mean pain score on the 1th, 2th, 3th, 7th, 14th
      days, 3th months and 6th months postoperative. RESULTS: Both groups were similar
      in clinical characteristics, there were no perioperative death in two groups. In
      the 1th, 2th, 7th, 14th days and 3th, 6th months postoperative, the NRS score of
      the single port group was superior, and the difference was significant compared
      with the triple port (P<0.05). There was no statistically significant difference
      between the two groups in operative time, blood loss, postoperative
      hospitalization time, duration of chest tube, the NRS scores in the 3 d (P>0.05).
      Univariate and multivariate analysis of the occurrence on the chronic pain showed
      that the operation time, surgical procedure and the 14th NRS score were risk
      factors for chronic pain (P<0.05). CONCLUSIONS: The single port thoracoscopic
      surgery has an advantage in the incidence of acute and chronic pain in patients
      with non-small cell lung cancer. Shorter operative time can reduce the occurrence
      of chronic pain. The 14th day NRS score is a risk factor for chronic pain
      postoperative.

PMID- 29587907
TI  - [Is Uniportal More Advantageous Than Three Portal in Alleviating Acute and
      Chronic Pain after Lobectomy?]

PMID- 29587908
TI  - [To Explore Clinical Value of Single-port Video-assisted Thoracoscopic Surgery
      ?in Elderly Patients with Non-small Cell Lung Cancer: Lobectomy, Segmentectomy
      ?and Lobectomy vs Segmentectomy].
AB  - BACKGROUND: The morbidity of lung cancer has long been the highest in cancer.
      Stage I, stage II and partly of stage III non-small cell lung cancer (NSCLC) are
      mainly treated by surgery. Lobectomy and segmentectomy both are common lung
      resection methods. Video-assisted thoracoscopic surgery (VATS) has been widely
      used in clinical, and the application of single-portvideo-assisted thoracoscopic
      surgery (SP VATS) has gradually been recognized and accepted by professors. With
      increasing degree of eldly in society, eldly patients already have become
      inceasingly difficulties in the diagnosis and treatment of NSCLC. The aim of this
      study is to explore and analyze clinical value of SP VATS lobectomy and
      segmentectomy in elderly patients with NSCLC. METHODS: In this retrospective
      observational study, the outcomes of 417 consecutive patients who had undergone
      SP VATS anatomic segmentectomy or lobectomy for NSCLC from May 2014 to December
      2016 on department of thoracic surgery in Fujian Medical University Affiliated
      Union Hospital were examined, including 139 elderly-case (lobectomy vs
      segmentectomy: 124 vs 15) and 278 nonelderly-case (lobectomy vs segmentectomy:
      248 vs 30). The condition of perioperative period and postoperative short-time
      recovery could be compared with lobectomy and segmentectomy between elderly and
      nonelderly cases and lobectomy and segmentectomy in elderly cases. RESULTS: The
      morbidty of preoperative complications was significant difference (P<0.05) in
      comparing with elderly and non-elderly patients with NSCLC either in SP VATS
      anatomic segmentectomy orlobectomy, except others is no significant difference
      (P>0.05). Numbers of dissected lymph nodes and mediastinal nodal stations of SP
      VATS lobectomy in elderly patients with NSCLC were more than segmentectomy
      (P<0.05), which were (7.61+/-0.21) vs (20.39+/-0.97) and (5.60+/-0.35) vs
      (15.40+/-2.64). But there was not significant difference between two elderly
      groups of SP VATS lobectomy and anatomic segmentectomy in age, morbidty of
      preoperative complications, average operation time and intraoperative blood loss
      (P>0.05). Postoperative drainage volume [(1,150.15+/-140.02) mL vs (853.53+/
      177.04) mL] and duration [(7.00+/-1.31) d vs (5.00+/-0.74) d], duration of
      postoperative hospital stay [(3.18+/-1.32) d vs (5.04+/-1.30) d], costs [(70.06+/
      5.23) thousands yuan vs (61.20+/-5.22) thousands yuan ] or postoperative
      complications (5.97% vs 20.00%)(P>0.05). Notwithstanding, group of SP VATS
      anatomic segmentectomy found more postoperative atrialfibrillation and the vein
      thrombosis of lower limbs (P<0.05). CONCLUSIONS: Elderly patients having more
      basic diseases and taking increasely risk of postoperative complications. SP VATS
      anatomic segmentectomy andlobectomy do not increase the risk of elderly patients
      with surgery. SP VATS segmentectomy is as safe and effective as SP VATS lobectomy
      in elderly patients, who fit to undergo SP VATS segmentectomy seem to get as same
      short-time effect as SP VATS lobectomy.

PMID- 29587909
TI  - [Current Status and Development of Research on Thoracoscopic Segmentectomy for
      Non-small Cell Lung Cancer].

PMID- 29587910
TI  - [Is Uniportal Less Invasive Than Multi--Portal Regarding VATS Lobectomy?]

PMID- 29587912
TI  - [Multi-center Retrospective Study for Rare Cases is Recommended].

PMID- 29587911
TI  - [Observation - An Favorable Option Forthoracic Dissemination Patients with Lung
      Adenocarcinoma or Squamous Carcinoma].
AB  - BACKGROUND: Surgery was not standard-of-care of patients with advanced lung
      cancer. However, a serial of retrospective studies demonstrated that thoracic
      dissemination (M1a) patients could benefit from contraindicated surgery. After
      non-standard treatment, how should these patients choose following treatment
      approaches? Herein, we conducted this retrospective study to explore subsequent
      optimal treatment approaches. METHODS: Different therapeutic approaches were
      evaluated by comparing progression-free survival (PFS), overall survival (OS),
      time to treatment interval (TTI) using the Kaplan-Meier method and Log-rank test.
      A Cox proportional hazards regression model was used for multivariate analysis.
      RESULTS: 141 eligible were enrolled. The median PFS of chemotherapy group,
      targeted therapy group and observation group were 14.7, 41.0 and 31.0 months,
      respectively (95%CI: 19.01-26.01; P<0.001). There was no significantly
      statistically difference between median PFS of targeted group and observation
      group (P=0.006). The median OS were 39.0, 42.6 and 38.1 months (95%CI: 32.47
      45.33; P=0.478). The median PFS and OS of TTI<3 months and TTI >=3 months were
      15.2 months versus 31.0 months (95%CI: 19.01-26.06; P<0.001) and 41.7 months
      versus 38.7 months (95%CI: 32.47-45.33; P=0.714). Multivariate analyses revealed
      gender (P=0.027), lymph node status (P=0.036) and initial therapy (P<0.001) were
      independent prognostic factors for PFS. CONCLUSIONS: Observation did not shorten
      survival of thoracic dissemination patients with lung adenocarcinoma or squamous
      carcinoma, therefore, it could be an favorable option. But prospective randomized
      controlled study was needed to confirm its validity.

PMID- 29587913
TI  - [Could Surgery Play a Role in Stage IVa Lung Cancer with Intrapleural
      Dissemination?]

PMID- 29587914
TI  - [Surgical Treatment of Refractory Chest Tumors Assisted ?by Cardiopulmonary
      Bypass].
AB  - BACKGROUND: A retrospective review of the surgical treatment of refractory chest
      tumors involving the heart or large vessels with cardiopulmonary bypass (CPB).
      METHODS: To summarize 11 cases of chest tumor patients who had undergone
      cardiopulmonary bypass surgery from January 2008 to May 2017 in our hospital, and
      analyze the general condition, clinical characteristics, treatment methods,
      postoperative hospitalization time, complications and follow-up results of all
      patients. RESULTS: All 11 patients were operated with cardiopulmonary bypass.
      Total resection of tumors in 8 cases and most of the excision in 3 cases. 1 case
      of left atrial metastatic leiomyosarcoma were excised in the left atrium, and
      then the right lung resection was performed. 1 case of left lung central lung
      cancer resection through the median sternum incision. 2 cases underwent pulmonary
      artery repair at the same time, 3 cases underwent partial pericardiectomy and 3
      cases underwent pulmonary wedge resection at the same time. All the patients were
      effectively relieved after the operation. No death rate in hospital and 30 days
      after operation. 3 cases of postoperative pulmonary infection were recovered
      after the treatment of antibiotics. 1 case of lymphoma relapsed 6 months after
      surgery and died one year later. 1 case of pericardial fibrosarcoma had local
      recurrence and extensive metastasis at 13 months after operation, and died after
      15 months. 1 case of pulmonary leiomyosarcoma were found to have local recurrence
      15 months after the operation and were relieved after chemotherapy. The remaining
      8 patients survived, and no obvious recurrence and distant metastasis were found
      in the computed tomography (CT) examination. CONCLUSIONS: The CPB assisted
      surgical treatment can be performed for patient of refractory chest tumors
      involving the heart or large vessels. It can improve the surgical resection rate
      of refractory chest tumors, effectively alleviate the effects on respiratory and
      circulatory functions, and significantly prolong the survival period of these
      patients.

PMID- 29587915
TI  - [Application and Prospect of Extracorporeal Circulation in General Thoracic
      Surgery].

PMID- 29587916
TI  - [Surgical Treatment of Bronchial Stricture due to Endobronchial Tuberculosis:
      ?Results in 36 Consecutive Cases].
AB  - BACKGROUND: Bronchial tuberculosis is a common complication of pulmonary
      tuberculosis. The present report is to investigate and analyze the indication and
      efficacy of surgical treatment of bronchial stricture due to severe endobronchial
      tuberculosis, when the drug and endoscopic treatment were no effect. METHODS:
      Reviewed the clinical-pathological records documenting the surgical outcomes in
      36 bronchial stricture due to severe endobronchial tuberculosis who underwent
      lobectomy or pneumonectomy enrolled in our hospital between January 2000 and
      February 2016. Pneumonectomy in 8 cases, lobectomy in 23 cases, sleeve resection
      in 5 cases. RESULTS: No intraoperative or early postoperative death occurred. Six
      patients developed complications. All 6 cases recovered well after treatment.
      CONCLUSIONS: Surgical treatment is still the recommended treatment modatity for
      bronchial stricture caused by endobronchial tuberculosis due to its good results.
      It should be performed in time when the drug and intraluninal treatment were no
      effect for avoiding of being progeressed.

PMID- 29587917
TI  - [Surgical Treatment of Pulmonary Tuberculosis Should Be Emphasized].

PMID- 29587919
TI  - [Lung Cancer in Special Population Also Need Our Attention].

PMID- 29587918
TI  - [Individualized Comprehensive Therapy for the Lung Cancer Patients ?with HIV
      Infection].
AB  - BACKGROUND: To observe clinical features, clinical stagings, types ofpathology,
      treatment options and clinical effects of patients suffer from HIV infection
      combined with lung cancer, and also to provide guidance for individualized
      comprehensive treatment of HIV combined with lung cancer. METHODS: Through the
      retrospective analysis of 53 cases of HIV merger of lung cancer patients admitted
      in our department, 47 cases of non-small cell lung cancer (NSCLC), 6 cases of
      small cell lung cancer (SCLC), 24 cases accepted surgery combined chemotherapy,
      22 patients with simple chemotherapy, 7 cases give up treatment; 28 cases are in
      stages I-III, 25 cases are in stage IV; 24 patients received combined
      chemotherapy in 28 patients with stages I-III, 2 cases gave up treatment, 2 cases
      with severe chronic obstructive pulmonary disease (COPD) could not tolerate
      chemotherapy plus surgery. According to the situation of patients before highly
      active anti-retroviral therapy (HAART) treatment, patients who received HAART
      before treatment were divided into observation group (n=27), patients who did not
      receive HAART were divided into control group (n=19). The survival and the
      independent influencing factors between the two groups were analyzed. RESULTS:
      Among the 53 HIV infected cases a toal of 46 patients received treatment among 53
      cases of treatment in patients with lung cancer merger of HIV, there are no
      differences of 1 year survival rate, 2 years survival rate between observation
      group and control group; patients in I-III phase 1 year survival rate was 76.0%,
      2 years survival rate was 60.0%. Patients in IV phase 1 year survival rate was
      13.6%, 2 years survival rate was 0%. 24 patients with surgery combined
      chemotherapy 1 year survival rate was 83.3%, 2 years survival rate was 62.5%; 22
      cases treated with simple chemotherapy 1 year survival rate was 18.0%, 2 years
      survival rate was 0%. CONCLUSIONS: HIV merger in patients with lung cancer can
      improve the patients survival rate after different individualized comprehensive
      treatment, early surgery with combined chemotherapy has remarkable effect.

PMID- 29587921
TI  - [Early Surgical Intervention should be Used in the Management of Mediastinitis].

PMID- 29587922
TI  - [The Mediastinal Infection after Esophagectomy is Uncommon but Important].

PMID- 29587920
TI  - [Treatment Experience of Continuous Negative Pressure Drainage in the Acute
      Anterior Mediastinal Infection of Oropharyngeal Origined].
AB  - BACKGROUND: Mediastinal infection is a serious infection of mediastinal
      connective tissue, with more complications and higher mortality. Application of
      broad-spectrum antibiotics and nutritional support, early sufficient drainage is
      the key to successful treatment. In the mode of drainage, this paper discusses
      the application of continuous negative pressure drainage technique to treat acute
      anterior mediastinal infection of severe mouth pharynx source, and the good
      results are summarized and shared. METHODS: In January to December in 2017, a
      total of 17 cases treated acute mediastinal infection is derived from the throat,
      has formed a mediastinal abscess, surgery adopts retrosternal counterpart
      negative pressure drainage way, namely the sternum nest and free sternum xiphoid
      process under the incision on the first mediastinal clearance, make breakthrough
      and placed drainage device, suture closed wound, continuous negative pressure
      drainage, negative pressure using 3 cm-5 cm water column. RESULTS: Among the 17
      patients, 14 patients were relieved by continuous negative pressure drainage, and
      then the drainage tube was removed. In 2 cases, the infection broke into the
      right thoracic cavity, and the closed drainage caused the negative pressure to
      disappear, and the negative pressure drainage was replaced by the conventional
      drainage, and the drainage tube was removed after the drainage tube was clear.
      One patient had formed a mediastinal abscess incision drainage time later,
      complicated with septic shock and sepsis, resulting in the death of multiple
      organ failure. CONCLUSIONS: The traditional treatment of severe acute mediastinal
      infection is sternal incision and drainage. Continuous negative pressure drainage
      adequate drainage of mediastinal can relieve patients' pain, effusion, and avoid
      the dressing out repeatedly. It is an effective method. However, there are
      limitations in this method, which need to be further optimized.

PMID- 29587923
TI  - [Application of VSD in 6 Cases of Postoperative Infection?-A Clinical Experience
      Sharing].
AB  - BACKGROUND: Surgical site infection is one of the common postoperative
      complications of thoracic surgery, and its harm is related to infection degree
      and location. Light causes local pain, prolonged hospitalization and increased
      cost. Severe infection can lead to severe infection, even septic shock and life
      threatening. Therefore, proper treatment of incision infection can help to
      promote recovery, reduce the burden of disease and lay a good foundation for
      further treatment. The traditional surgical treatment of wound infection includes
      thorough drainage, intensive dressing change and antibiotic use. There are many
      shortcomings such as long treatment process, ineffective treatment effect and so
      on. The experience of using vacuum sealing drainage (VSD) in 6 cases of
      postoperative infection patients in our department is summarized in order to
      improve the traditional treatment of postoperative infection in patients after
      thoracic surgery. METHODS: The clinical data of patients with postoperative
      incision infection or fistula after thoracic surgery in our department were
      reviewed and summarized. 6 patients treated with VSD material for postoperative
      infection. The process and final clinical results of them were summarized and
      discussed. RESULTS: In this study, fever and wound exudation disappeared within 6
      h-10 h after VSD use, 5 cases of wound infection were obviously improved, the
      secretion disappeared and the granulation tissue grew well at the cutting edge of
      the operation, the second stage operation was performed to close the chest and
      skin. One patient was seriously infected, and the secretion was still more after
      VSD removal, reposition VSD device next time, the VSD device was removed 7 d
      later. The wound infection were obviously improved, the secretion disappeared and
      the granulation tissue grew well, close the chest and skin second stage. In all 6
      patients, the symptoms were relieved, the symptoms improved and the surgical
      incision healed well. In 2 patients with esophageal cancer, the average operation
      time was 427.5 min, the average hospitalization time was 40 d, the average number
      of times of dressing change was 8.5, the average total cost during
      hospitalization was 111,893.47 yuan patients with chronic empyema, the average
      operation time was 192.5 min. The average hospital stay was 27.75 days, the
      average number of times of dressing change was 5.5, and the average total
      expenditure during hospitalization was 48,237.71 yuan. CONCLUSIONS: VSD has a
      good effect on the treatment of postoperative incision infection patients in
      thoracic surgery. It can reduce the pain and burden of patients and ensure the
      quality of life of postoperative infected patients.

PMID- 29587924
TI  - [VSD - A Good Idea for the Management of Surgical Infection].

PMID- 29587925
TI  - [VSD Could Effectively Manage Surgical Infection].

PMID- 29587926
TI  - [President's Perspective].

PMID- 29587927
TI  - [New Concept of the Development of Modern Medicine: Make Full Use of the
      Internet, Large Data, and Artificial Intelligence].

PMID- 29587928
TI  - [A Decade's Review for the Foundation, Establishment and Development of Thoracic
      Surgeon Branch of Chinese Physicians' Association].

PMID- 29587929
TI  - [Preface].

PMID- 29587931
TI  - [Management Strategies of Pulmonary Ground Galss Nodule].
AB  - Pulmonary ground glass nodule (GGN) is a term of radiological manifestation,
      which may be malignant or benign. The management for pulmonary GGN remains
      controversial. Both Fleischner society and National Comprehensive Cancer Network
      (NCCN) panel updated the guideline for the management of GGN in 2017. Compared
      with previous versions, the indication for surgery or biopsy is stricter, and the
      recommended follow-up interval is prolonged. In clinical practice, the size of
      GGN component, the size of consolidation component, dynamic change during follow
      up and computed tomography (CT) value are the four factors that help surgeons to
      decide the timing of surgery. There are some misunderstandings for the management
      of GGN, such as the administration of antibiotics, the use of positron emission
      tomography-computed tomography (PET-CT), pure GGN adjacent to visceral pleura,
      and GGN with penetrating vessel. In conclusion, GGN is a kind of slowly growing
      lesion, which can be followed up safely.?.

PMID- 29587930
TI  - [Shanghai Pulmonary Hospital Experts Consensus on the Management of Ground-Glass
      Nodules Suspected as Lung Adenocarcinoma (Version 1)].
AB  - Background and objective As computed tomography (CT) screening for lung cancer
      becomes more common in China, so too does detection of pulmonary ground-glass
      nodules (GGNs). Although anumber of national or international guidelines about
      pulmonary GGNs have been published,most of these guidelines are produced by
      respiratory, oncology or radiology physicians, who might not fully understand the
      progress of modern minimal invasive thoracic surgery, and these current
      guidelines may overlook or underestimate the value of thoracic surgery in the
      management of pulmonary GGNs. In addition, the management for pre-invasive
      adenocarcinoma is still controversial. Based onthe available literature and
      experience from Shanghai Pulmonary Hospital, we composed this consensus about
      diagnosis and treatment of pulmonary GGNs. For lesions which are considered as
      adenocarcinoma in situ, chest thin layer CT scan follow-up is recommended and
      resection can only be adopt in some specific cases and excision should not exceed
      single segment resection. For lesions which are considered as minimal invasive
      adenocarcinoma, limited pulmonary resection or lobectomy is recommended. For
      lesions which are considered as early stage invasive adenocarcinoma, pulmonary
      resection is recommend and optimal surgical methods depend on whether ground
      glass component exist, location, volume and number of the lesions and physical
      status of patients. Principle of management of multiple pulmonary nodules is that
      primary lesions should be handled with priority, with secondary lesions taking
      into account.?.

PMID- 29587933
TI  - [What is Enhanced Recovery After Surgery: Humanity or Technology?]
AB  - The development of surgical techniques and the innovation of surgical instruments
      promote the changes in surgical methods, which in turn, leads to the reforms of
      surgical idea. The concept of enhanced recovery after surgery (ERAS) results in
      the surgery connotation switching from "to treat an illness" to "to save
      patients". ERAS also causes the change of surgery denotation from "only
      operation" to "enhance recovery". The concept of ERAS is derived from but not
      only restricted to the development of surgical techniques. Also, ERAS pays more
      attention to patients than disease and thinks more about patient safety and
      recovery than surgical technique. Specifically, ERAS has three advantages: first,
      ERAS attaches importance to multidisciplinary assessment (patient-oriented) and
      select appropriate (personalized) treatment and tries to decrease the rate of
      complication and mortality. Second, ERAS pays attention to preoperative
      preparation and high-risk prevention performed by multi-disciplinary
      collaboration in order to prevent complication and save cost for patients. Third,
      ERAS always focus on optimizing the process of perioperative period and trying to
      change the working habits of surgeons and the old cooperation mode among doctors,
      nurses and rehabilitation physicians. To sum up, the goal is to apply the concept
      of ERAS to all the links of perioperative period and try hard to decrease
      patients' stress and pain, which finally helps doctors fulfill the ultimate aims
      of "no pain and no risk".?.

PMID- 29587932
TI  - [The Clinical and Molecular Characteristics of Adenocarcinoma Presented ?by Multi
      focal GGO].
AB  - Due to emphasis on early screening for lung cancer, the detection rate of
      multiple ground glass opacities (GGOs) on computed tomography (CT) image
      increases in recent years, and research on multifocal adenocarcinomas presented
      by GGOs has been thriving. It is more common in women and non-smokers and has
      excellent prognosis both in patients with natural history and after surgery.
      These clinical features suggest that it is likely to be a distinct disease
      entity. From the perspective of molecular genetics, lesions in the same
      individual are likely to have distinct clonal features. Therefore, genetic
      heterogeneity is the most prominent feature of multifocal pulmonary
      adenocarcinomas with GGOs. The genetic heterogeneity is expected to assist the
      diagnosis of multifocal pulmonary adenocarcinoma and intrapulmonary metastasis,
      and also suggests that genetic testing of the GGO lesions is of great therapeutic
      significance. Some GGO lesions may harvest the similar clonal feature, which
      provide new evidence for the theory of spread through air spaces (STAS).?.

PMID- 29587934
TI  - [Reflection on the Biological Significance of Minimally Invasive Surgery for Lung
      Cancer].
AB  - Minimal invasive surgery with short operation time and enhanced recovery after
      surgery can truly achieve biological minimal invasiveness. The minimal invasive
      lung cancer surgery includes several kinds, such as uni-portal video-assisted
      thoracoscopic surgery (VATS) and multi-portal VATS. Robotic-assisted thoracic
      surgery (RATS) can be categorized into multi-portal VATS. As a frontier
      technology of minimal invasive surgical technique, surgical robotic system has
      been broadly applied in many areas. The average RATS operation time is (91.51+/
      30.80) min among our team, which is much shorter than reported uni-portal VATS
      operation time. For now, RATS has some drawbacks and is lacking of national
      practice guidelines, which, we believe, will be solved by technology development
      and large-scale randomized controlled trials. ?.

PMID- 29587935
TI  - [The Argument and Consensus of Lymphadenectomy on Lung Cancer Surgery].
AB  - Lymph node metastasis is an important route of metastasis of lung cancer.
      Lymphadenectomy has become the standard surgical procedure for lung cancer. The
      way of intraoperative lymph node assessment also affects the prognosis and
      treatment strategy of lung cancer. In clinical practice, the way of
      intraoperative lymph node assessment ranges from selected lymph node biopsy to
      extended lymph node dissection. The advantages and disadvantages of different
      lymph node assessment are still controversial. In this article, the argument and
      consensus of lymphadenectomy on lung cancer operation are summarized.

PMID- 29587936
TI  - [Experience and Progress Processing Policy of Simultaneous Multiple Primary ?Lung
      Cancer].
AB  - BACKGROUND: Simultaneity multiple primary lung cancer always is a rare disease,
      but in recent years due to the progress of the diagnosis and treatment means
      detection rate increased. This study summarized the clinical data of 31 cases of
      synchronous multiple primary lung cancer (sMPLC) analysis, further to explore the
      diagnosis, treatment and prognosis of MPLC. METHODS: Sum up the clinical data of
      31 cases of simultaneous multiple primary lung cancer, the diagnostic method,
      surgical methods, pathology, were retrospectively analyzed. RESULTS: All the
      patients are thoracoscope surgery, no deaths. Thin high resolution computed
      tomography (CT) in preoperative found multiple lung nodules. Lesions located in
      the same side of the same period surgical treatment, the operation method is
      given priority to with under the thoracoscope lung + the lobectomy; Lesions
      located in bilateral, all staged operation, the time interval for 3 months-4
      months. CONCLUSIONS: Thin layer distinguish CT preoperative diagnosis is the best
      way to simultaneous multiple primary lung cancer. Multiple primary lung cancer
      incidence of ipsilateral lung at the same time higher than that of bilateral lung
      (23:8), type, around 94%, the most common histology to adenocarcinoma, 80.6%
      (25/31). Primary lesions under thoracoscope lobectomy plus the lobectomy of
      secondary lesions is the most commonly used.

PMID- 29587937
TI  - [Diagnosis and Treatment for Multiple Primary Lung Cancer].

PMID- 29587938
TI  - [A Retrospective Study of Mean Computed Tomography Value to Predict ?the Tumor
      Invasiveness in AAH and Clinical Stage Ia Lung Cancer].
AB  - BACKGROUND: Recently, the detectable rate of ground-glass opacity (GGO ) was
      significantly increased, a appropriate diagnosis before clinic treatment tends to
      be important for patients with GGO lesions. The aim of this study is to validate
      the ability of the mean computed tomography (m-CT) value to predict tumor
      invasiveness, and compared with other measurements such as Max CT value, GGO
      size, solid size of GGO and C/T ratio (consolid/tumor ratio, C/T) to find out the
      best measurement to predict tumor invasiveness. METHODS: A retrospective study
      was conducted of 129 patients who recieved lobectomy and were pathological
      confirmed as atypical adenomatous pyperplasia (AAH) or clinical stage Ia lung
      cance in our center between January 2012 and December 2013. Of those 129
      patients, the number of patients of AAH, AIS, AIS and invasive adenocarcinoma
      were 43, 26, 17 and 43, respectively. We defined AAH and AIS as noninvasive
      cancer (NC), MIA and invasive adenocarcinoma were categorized as invasive
      cancer(IC). We used receiver operating characteristic (ROC) curve analysis to
      compare the ability to predict tumor invasiveness between m-CT value,
      consolidation/tumor ratio, tumor size and solid size of tumor. Multiple logistic
      regression analyses were performed to determine the independent variables for
      prediction of pathologic more invasive lung cancer. RESULTS: 129 patients were
      enrolled in our study (59 male and 70 female), the patients were a median age of
      (62.0+/-8.6) years (range, 44 to 82 years). The two groups were similar in terms
      of age, sex, differentiation (P>0.05). ROC curve analysis was performed to
      determine the appropriate cutoff value and area under the cure (AUC). The cutoff
      value of solid tumor size, tumor size, C/T ratio, m-CT value and Max CT value
      were 9.4 mm, 15.3 mm, 47.5%, -469.0 HU and -35.0 HU, respectively. The AUC of
      those variate were 0.89, 0.79, 0.82, 0.90, 0.85, respectively. When compared the
      clinical and radiologic data between two groups, we found the IC group was
      strongly associated with a high m-CT value, high Max CT value, high C/T ratio and
      large tumor size. Gender, solid tumor size, tumor size, C/T ratio, m-CT value and
      MaxCT value were selected factor for multivariate analysis, when using the
      preoperatively determined variables to predict the tumor invasiveness, revealed
      that tumor size, C/T ratio, m-CT value and Max CT value were independent
      predictive factors of IC. CONCLUSIONS: The musurements of Max CT value, GGO size,
      solid size of GGO and C/T ratio were significantly correlated with tumor
      invasiveness, and the evaluation of m-CT value is most useful musurement in
      predicting more invasive lung cancer.

PMID- 29587939
TI  - [The Diagnosis of Pure/Semi-solid GGN Is Not Easy].

PMID- 29587941
TI  - [More Evidence is Needed for Postoperative Follow-up Strategy of Early Stage Lung
      Cancer].

PMID- 29587940
TI  - [Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC
      Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after
      Lobectomy].
AB  - BACKGROUND: Currently, there is no consensus on the follow-up strategy (follow-up
      time interval and content) of non-small cell lung cancer (NSCLC) in the world,
      and the relevant clinical evidence is also very limited. In this study, we aimed
      to summarize the recurrence/metastasis sites and timings of stage I NSCLC
      patients based on their follow-up data, aiming to provide a basis of follow-up
      time interval and content for this group of patients. METHODS: We retrospectively
      analyzed the 416 stage I NSCLC patients that underwent continuous anatomic
      lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database.
      According to the recurrence/metastasis sites and timings, the long term follow-up
      time interval and content were explored. RESULTS: The 5-yr disease free survival
      (DFS) and overall survival (OS) in the whole group were 82.4% and 85.4%,
      respectively. There were 76 cases (18.3%) had recurrence/metastasis during follow
      up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%),
      followed by brain metastasis (20 cases, 4.8%), bone metastasis (12 cases, 2.9%),
      and mediastinal lymph node metastasis (12 cases, 2.9%). Among the factors that
      could influence recurrence/metastasis, patients with pT2a suffered from a higher
      recurrence/metastasis rate compared to patients with pT1 (P=0.006), with 5-yr DFS
      being 73.8% and 87.3%, respectively (P=0.002), and the 5-yr OS being 77.7% and
      90.3%, respectively (P=0.011). CONCLUSIONS: The commonest recurrence/metastasis
      sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal
      lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that
      between 3 years and 5 years. The follow-up frequencies and content within 2 years
      could be adjusted according to T stages.

PMID- 29587942
TI  - [Postoperative Follow-up Should Not Be Neglected].

PMID- 29587944
TI  - [Robotic-assisted Thoracic Surgery is Expected to be Feasible for Widely Utility
      in Thoracic Disease].

PMID- 29587943
TI  - [A Paired Case Controlled Study Comparing the Short-term Outcomes of Da Vinci
      RATS and VATS Approach for Non-small Cell Lung Cancer].
AB  - BACKGROUND: Da Vinci Surgical System is one of the greatest inventions of the
      20th century, which represents the development direction of the precise minimally
      invasive surgical techniques, the aim of this study was to comparing the short
      term outcomes between da Vinci robot-assisted lobectomy and video-assisted
      thoracic surgery (VATS) lobectomy for non-small cell lung cancer. METHODS: 45
      pairs of non-small cell lung cancer patients underwent pulmonary lobectomy with
      da Vinci Robotic assisted thoracoscopic (RATS) and VATS approach during the same
      period from January 2014 to January 2017. The operative time, estimated blood
      loss (EBL), total number and total groups of dissected lymph nodes, postoperative
      duration of drainage, the first day volume of drainage, total volume of drainage
      were compared. RESULTS: No perioperative death and convertion to thoracotomy
      occured in both groups. There were significant difference between RATS group and
      VATS group in EBL [(50.30+/-32.33) mL vs (208.60+/-132.63) mL], the first day
      volume of drainage [(275.00+/-145.42) mL vs (347.60+/-125.80) mL], the dissected
      total number [(22.67+/-9.67) vs (15.51+/-5.41)] and total team [(6.31+/-1.43) vs
      (4.91+/-1.04)] of lymph node. There were no significant difference in other
      outcomes. CONCLUSIONS: RATS is safe and effective and took better short-outcomes
      than VATS in non-small cell lung cancer.

PMID- 29587945
TI  - [The Long Term Efficacy of Robotic Surgery for Cancer is Worth Expecting].

PMID- 29587946
TI  - [Impact of Chronic Obstructive Pulmonary Disease on Risk of Recurrence in
      Patients with Resected Non-small Cell Lung Cancer].
AB  - BACKGROUND: Lung cancer and chronic obstructive pulmonary disease (COPD) are both
      common diseases in respiratory system and the leading causes of deaths worldwide.
      The purpose of this study was to determine whether the severity of COPD affects
      long-term survival in non-small cell lung cancer (NSCLC) patients after surgical
      resection. METHODS: A retrospective research was performed on 421 consecutive
      patients who had undergone lobectomy for NSCLC. Classification of COPD severity
      was based on guidelines of the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD). Characteristics among the three subgroups were compared and
      recurrence-free survivals were analyzed. RESULTS: A total of 172 patients were
      diagnosed with COPD, 124 as mild (GOLD-1), 46 as moderate(GOLD-2), and 2 as
      severe (GOLD-3). The frequencies of recurrence were significantly higher in
      higher COPD grades group (P<0.001). Recurrence-free survival at five years were
      78.1%, 70.4%, and 46.4% in Non-COPD, GOLD-1 COPD, and GOLD-2/3 COPD groups,
      respectively (P<0.001). In univariate analysis, age, gender, smoking history,
      COPD severity, tumor size, histology and pathological stage were associated with
      recurrence-free survival. Multivariate analyses showed that older age, male, GOLD
      2/3 COPD, and advanced stage were independent risk factors associated with
      recurrence-free survival. CONCLUSIONS: NSCLC patients with COPD are at higher
      risk for postoperative recurrence, and moderate/severe COPD is an independent
      unfavorable prognostic factor. The severity of COPD based on pulmonary function
      test can be a useful indicator to identify patients at high risk for recurrence.
      Therefore, it can contribute to adequate selection of the appropriate
      individualized treatment.

PMID- 29587947
TI  - [Some Valuable Issues Regarding the Surgery for Lung Cancer Combined with COPD
      and the Postoperative Recurrence Risk].

PMID- 29587948
TI  - [Analysis of Prolonged Hospitalizations (Longer than 7 days): 115 Lung Cancer
      ?Patients after Video Assistant Thoracic Surgery (VATS)].
AB  - BACKGROUND: Thoracoscopic surgery has gradually become the major procedure for
      lung cancer surgery in our department. Its characteristics are minimal trauma and
      quick recovery, which make approximately 90% of patients discharge from the
      hospital after surgery. However, the postoperative complications still happen now
      and then. We analyzed the patients who had been hospitalized for longer than 7
      days after thoracoscopic lung cancer surgery, aiming to summarize the types and
      risk factors of complications, and improve postoperative safety of patients.
      METHODS: The data were come from the prospective database of Thoracic Surgery
      Unit One in Peking Cancer Hospital, and patients that underwent thoracoscopic
      pulmonary surgery between Jan. 2010 and Dec. 2014 with length of stay more than 7
      days were included in the study. The classifications of the complications were
      investigated and graded as mild or severe complications according to modified
      Claviengrading, the relationship between clinical factors and degrees of
      complications was also analyzed. RESULTS: The hospitalization of 115 cases were
      longer than 7 days after surgery, accounting for 10.3% (115/1,112) of the whole
      patients that underwent surgery during the same period. Eighty-one cases had mild
      complications, accounting for 7.3% (81/1,112) of the whole cases that underwent
      surgery during the same period and 70.4% (81/115) of the cases with prolonged
      length of stay; the proportions of severe complications in both groups were 3.1%
      (34/1,112) and 29.6% (34/115), respectively; and the proportions of complications
      that caused perioperative deaths were 0.18% (2/1112) and 1.7% (2/115),
      respectively. Among all the postoperative complications, the most common was air
      leakage for more than 5 days after surgery, with a total of 20 cases (1.8% and
      17.4%). The other common complications were: atelectasis (19 cases, 1.7% and
      16.5%), pulmonary infection (18 cases, 1.6% and 15.7%), etc. The less common
      complications was bronchopleural fistula (4 cases, 0.36% and 3.5%) with very high
      risk, and 2 cases died perioperatively due to the combination of acute
      respiratory distresssyndrome (ARDS). In the clinical factors, only preoperative
      low pulmonary function (FEV1%<70%) was the potential risk factor for
      postoperative severe complications (45.8% vs 23.6%, P=0.038). There was no
      significant difference either regarding the 5 year disease free survival or the 5
      year overall survival between mild complication group and severe complication
      group, with 5 year DFS being 52.2% and 51.9%, respectively (P=0.894) , and 5 year
      overall survival being 64.0% and 53.5%, respectively (P=0.673). CONCLUSIONS:
      Continuous postoperative air leakage, atelectasis and pulmonary infections were
      the major causes for prolonged hospitalization after thoracoscopic surgery for
      lung cancer, and bronchopleural fistula was the most perilous complications.
      Patients with low preoperative pulmonary function were more likely to have severe
      postoperative complication, however, this would not influence the long term
      survival of the patients.

PMID- 29587949
TI  - [The Prevention and Management Strategy for Postoperative Complications after
      Thoracoscopic Surgery of Lung Cancer].

PMID- 29587950
TI  - [The Influence of Surgical Complications on Cancer Patients' Survival Should Be
      Emphasized].

PMID- 29587952
TI  - [Bronchopleural Fistula - the Pulmonary Surgery Complications that Should Be
      Emphasized by Thoracic Surgeons].

PMID- 29587951
TI  - [Omentum Transplantation in Thorax to Cover Bronchial Stump as Treatment of
      ?Bronchopleural Fistula After Pulmonary Resection: Report of 6 Cases'
      Experience].
AB  - BACKGROUND: Bronchial pleural fistula (BPF) is a common complication after
      thoracic surgery for lung resection. Clinical treatment is complex and the effect
      is poor. The treatment of BPF after lung resection has plagued thoracic surgeons.
      We reviewed retrospectively the clinical and follow-up data of 6 patients in our
      hospital who underwent the omentum transplantation in thorax to cover bronchial
      stump as treatment of BPF after pulmonary resection to analyze why BPF occurs and
      describe this treatment method. We intend to discuss and evaluate the
      feasibility, safety and small sample success rate ofthis treatment method.
      METHODS: During August 2016 to February 2018, six patients in our hospital
      underwent remedial open thoracotomy and omentum transplantation in pleura space
      to cover bronchial stump as treatment of bronchopleural fistula after pulmonary
      resection. Four patients had undergone a prior pneumonectomy and two patients had
      undergone a prior lobectomy (the residual lungs were resected with the main
      bronchus cut by endoscopic stapler during the reoperation). The bronchial stumps
      were sutured by 4-0 string with needle and covered by omentums, which were
      transplanted in pleura space from the cardiophrenic angle. Postoperatively, the
      pleura space was irrigated and drained. Summarize the clinical effect and
      technique learning points. RESULTS: The patients were all males, aged 61 to 73
      years (median age: 66). BPF occurred from postoperative day 10 to 45 (median
      postoperative day 25). The reoperation was finished in 80 mins-150 mins (median
      110 mins). Total blood loss was 200 mL-1,000 mL (median 450 mL). These patients
      were discharged on postoperative day 12-17 (median 14 days), and there was no
      more complications associated with bronchopleural fistula. All six patients'
      bronchial stumps were well closed (100%) and have recovered well during the
      follow-up period, which lasted 1 month-18 months. CONCLUSIONS: Remedial operation
      should be performed as soon as possible when BPF after pulmonary resection
      diagnosed. Excellent prognoses can be achieved by omentum which is easy to get
      transplanted in thorax to cover bronchial stump as treatment in patients with BPF
      after pulmonary resection those who can tolerate reoperation.

PMID- 29587954
TI  - [Psychiatric symptoms in patients with Huntington's disease].
AB  - Huntington's disease is an inherited neuropsychiatric disorder characterized by a
      triad of symptoms: motor, cognitive and psychiatric. Psychiatric symptoms occur
      prior to the motor symptoms in approximately 50% of the cases, and knowledge of
      the psychiatric symptoms is essential in making an early diagnosis. In this
      article, we argue that further knowledge of the genetic background of
      Huntington's disease may contribute to a better understanding of the polygenetic
      psychiatric diseases such as schizophrenia and bipolar affective disorder.

PMID- 29587953
TI  - [Nrf2 and Keap1 Abnormalities in 104 Lung Adenocarcinoma Cases and Association
      with Clinicopathologic Features].
AB  - BACKGROUND: There are significantly interindividual variations of the expression
      level of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or Kelch-like ECH
      associated protein 1 (Keap1) in our previous studies. It has been proven that
      Nrf2 or Keap1 is related to resistance of chemotherapeutic drugs and/or epidermal
      growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, the
      expression of Nrf2 and Keap1 in lung adenocarcinoma patients with different
      "driver gene" is not clear. The aim of this study is to investigate the protein
      expression level of Nrf2 and Keap1 in lung adenocarcinoma and to elucidate the
      correlation between Nrf2 or Keap1 expression and the status of EGFR gene mutation
      and to determine the effects of Nrf2 and Keap1 on the patients. METHODS:
      Immunohistochemical analysis of Nrf2 and Keap1 in tumor specimens was performed
      in a total of 104 lung adenocarcinoma patients with the status of EGFR gene
      mutations or EGFR wide-type. RESULTS: The Nrf2 positive rate was 71.2% and Keap1
      high expression rate was 34.6% in 104 patients. The Nrf2 positive rate
      significantly correlated with gender, stage and status of EGFR gene mutation
      (P<0.05), but not with age, smoking, differentiation and subtype of lung
      adenocarcinoma (P>0.05). The high expression of Keap1 was not significantly
      correlated with gender, age, smoking, differentiation, subtype of lung
      adenocarcinoma and status of EGFR gene mutation (P>0.05). The progression -free
      survival (PFS) and overall survival (OS) of the patients treated by EGFR-TKIs
      were significantly correlated with the expression level of Nrf2, but not with
      Keap1. The PFS and OS of the patients with Nrf2 high expression were
      significantly shorter than the patients with low/negative expression (P<0.05).
      Furthermore, Nrf2 high expression was the independent predictive factor for EGFR
      TKIs induced PFS and OS (P<0.05). CONCLUSIONS: The Nrf2 positive rate
      significantly correlated with the status of EGFR gene mutation in lung
      adenocarcinoma. The Nrf2 high expression significantly correlated with PFS and OS
      of EGFR-TKIs. Therefore, Nrf2 may be a biomarker for predicting response of EGFR
      TKIs and a potential target for overcoming resistance of EGFR-TKIs.

PMID- 29587955
TI  - [Small amounts of milk added to coffee or tea can be allowed before surgery].
AB  - The ingestion of milk is not allowed within six hours before elective procedures
      requiring anaesthesia or sedation, because milk is considered a solid food.
      However, the impact of milk suspended in coffee or tea consumed up to two hours
      before anaesthesia is less certain, yet fasting guidelines demand surgery to be
      delayed or rescheduled. Studies investigating ingestion of liquids with small
      amounts of milk have not demonstrated delayed emptying of the stomach, thereby
      increasing the risk of aspiration in elective procedures. Maybe it is time to
      adjust the fasting recommendations.

PMID- 29587956
TI  - [The blood-brain barrier in ageing persons].
AB  - Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier
      (BBB). The permeability of the BBB increases with increasing age and
      neurovascular and neurodegenerative diseases. Major defects of the BBB can be
      initiated by increased permeability to plasma proteins in small arteriosclerotic
      arteries and release of proteins from degenerating neurons into the brain
      extracellular space. These proteins deposit in perivascular spaces, and
      subsequently negatively influence the BECs leading to decreased expression of
      barrier proteins. Detection of BBB defects by the use of non-invasive techniques
      is relevant for clinical use in settings with advanced age and severe brain
      disorders.

PMID- 29587957
TI  - [Epilepsy surgery].
AB  - Surgery is the only treatment option with the potential to cure epilepsy. This
      review is a description of the multidisciplinary and multimodal presurgical
      evaluation process and the outcome of the Danish epilepsy surgery programme. The
      outcome aligns with international results and serious complications to surgery
      are very rare. The annual number of operations per capita compares to
      neighbouring countries and is equally distributed across Denmark. In accordance
      with international recommendations, Danish drug-resistant patients should be
      referred to epilepsy surgery evaluation at an early stage of the disease.

PMID- 29587958
TI  - [Early detection of psychosis].
AB  - In 2012, Region Zealand launched the first early detection of psychosis team in
      Denmark. The motivation behind was the accumulating evidence of early detection
      of psychosis being of great importance for the outcome. This is a description of
      the experiences with establishing an early detection team in a Danish context and
      the outline of a strategy for informing the general population about psychosis.
      Furthermore, the first results from the research projects are presented. It is
      concluded, that early detection teams could be introduced throughout Denmark with
      great advantage.

PMID- 29587959
TI  - CUP Syndrome-Metastatic Malignancy with Unknown Primary Tumor.
AB  - BACKGROUND: 2-4% of newly diagnosed cases of malignant disease involve cancer of
      unknown primary (CUP). This mixed entity is one of the 6 most common types of
      malignant disease in Germany. Highly refined treatment strategies can now be
      offered to patients with CUP. METHODS: This review is based on pertinent
      publications retrieved by a selective search in PubMed with an emphasis on
      articles from the past decade. The current guidelines and recommendations of
      specialty societies were also considered in the evaluation. RESULTS: CUP most
      commonly manifests itself as metastases to the lymph nodes, lungs, liver, or
      bones. With the aid of imaging studies, including functional hybrid imaging and
      further medical examination, a primary tumor can be discovered in up to 40% of
      patients initially diagnosed with CUP. Immunohistochemistry guided by
      histomorphology often enables precise characterization of the lesion and can be
      supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The
      most commonly detected types of primary tumor are cancers of the lung, pancreas,
      liver, and biliary system. For patients with local metastases, surgical resection
      or radiotherapy with curative intent is usually indicated, sometimes in the
      framework of a multimodal treatment concept. The median 2-year survival of
      patients with disseminated CUP is only 20%. For such patients, specific types of
      systemic therapy are recommended on the basis of the diagnostic characterization
      of the disease. Immune-modulatory antibodies can be effective, particularly in
      the treatment of CUP that has been characterized with biomarkers, but should
      still be considered experimental at present. CONCLUSION: A combination of
      conventional and innovative diagnostic methods enables the provision of highly
      refined therapeutic strategies to patients with CUP who are undergoing treatment
      in interdisciplinary cancer centers.

PMID- 29587960
TI  - Cluster-Randomized Studies.
AB  - BACKGROUND: Cluster-randomized trials (CRT) are needed to compare interventions
      that are allocated to entire groups of subjects, rather than to individuals.
      Publications about CRT have become steadily more common over the past decade.
      Readers of such publications should be able to categorize and interpret the
      findings of CRT correctly while considering the methodological requirements
      applicable to this type of study. METHODS: This review is based on a selection of
      pertinent literature and on the authors' expertise. CRT-specific methodological
      aspects of the planning, performance, and interpretation of studies are
      discussed. RESULTS: Readers of publications on CRT should check whether due
      consideration has been given to correlations within and between the clusters
      during the planning of the study. These correlations enable the determination
      whether persons within a cluster resemble each other more closely, or respond
      more similarly to the study intervention, than persons drawn from different
      clusters. It should also be checked whether the randomization for the study has
      been carried out with such methods as stratification and covariate-adjusted
      randomization. CRT can be analyzed on either the individual or the cluster level.
      The rationale for the choice of a clusterrandomized design should be explained,
      and intracluster correlation coefficients (ICC) should be reported as an aid to
      the planning of future studies. Particular requirements are also described in an
      extended version of the CONSORT guidelines that has been developed specifically
      for CRT. CONCLUSION: Readers of publications on CRT should be aware of the
      special requirements mentioned above with respect to the design, performance, and
      analysis of this type of study as opposed to individually randomized studies. If
      no special techniques are applied in the design, performance, and analysis of a
      CRT, or if the assumptions underlying each of these steps have not been properly
      checked, then the findings of the study may well be misleading.

PMID- 29587961
TI  - Liquid Biopsy in Tumor Genetic Diagnosis.
AB  - BACKGROUND: Liquid biopsy involves the analysis of cell-free nucleic acids,
      mainly circulating free DNA (cfDNA), in bodily fluids such as blood. The
      obtaining of specimens is easier for patients and less invasive than tissue
      biopsy, but the method has certain limitations. METHODS: This review is based on
      pertinent publications retrieved by a selective literature search. RESULTS:
      Because the concentration of cfDNA in plasma is less than 0.001%, special
      amplifying techniques must be used to enable a search for specific mutations.
      Liquid biopsy can be used in patients with non-small cell lung cancer (NSCLC) if
      no tissue is available for biopsy; when performed for this indication, it has 67%
      sensitivity and 94% specificity. If liquid biopsy does not reveal a mutation,
      this may be due either to the absence of the mutation in the tumor or to the
      inadequate sensitivity of the measuring technique. This uncertainty associated
      with negative findings can be reduced by the simultaneous demonstration of
      reference mutations derived from a primary tumor tissue analysis. In comparison
      to tissue studies, the search for tumor-specific mutations by liquid biopsy is
      70% sensitive and 69% specific; this corresponds to a positive predictive value
      of 86% and a negative predictive value of 46%. CONCLUSION: Liquid biopsy and
      tumor tissue analysis are complementary, rather than alternative, techniques for
      therapeutically relevant genetic investigation of tumors. Comparative studies are
      needed so that further indications can be determined for liquid biopsy in the
      diagnostic evaluation of cancer.

PMID- 29587962
TI  - Reply to: "Comments and question on "Selective inhibition of endothelial NF
      kappaB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis
      in mice"".

PMID- 29587963
TI  - Risk of Skin Cancer Associated With Narrowband UV-B Phototherapy.

PMID- 29587964
TI  - Improving the Quality of Life of Patients With Actinic Keratosis.

PMID- 29587965
TI  - Cervical Cellulitis of Odontogenic Origin.

PMID- 29587966
TI  - Total intracorporeal anastomosis for right hemicolectomy: Experience from a
      Canadian center.
AB  - BACKGROUND: Laparoscopic right hemicolectomy (LRHC) techniques have varied in the
      approach to anastomosis. We compared outcomes of laparoscopic right hemicolectomy
      with extracorporeal anastomosis (ECA) versus intracorporeal anastomosis (ICA).
      METHODS: We retrospectively reviewed all LRHCs conducted at Richmond Hospital
      between January 2015 and October 2017. We compared the demographic, pathologic,
      intraoperative, and postoperative data. RESULTS: 74 LRHCs were included during
      the study period: 56 ECA and 18 ICA. The groups were comparable in age, gender,
      tumor staging, and tumor location. Incidence of clinical ileus was significantly
      less for ICA (0% vs. 21%, p = 0.032). Mean length of stay was significantly
      shorter for ICA (3.13 vs. 4.82 days, p = 0.003). There was no difference between
      ICA and ECA in mean operative time (158 vs. 145 min, p = 0.087), surgical site
      infections (6% vs. 4%, p = 1.0), emergency department visits within 30 days (5%
      vs. 6%, p = 1.0), and hospital readmission within 30 days (4% vs 0%, p = 1.0).
      There were no incidences of anastomotic leaks, perioperative deaths, or
      cardiopulmonary complications in either group. CONCLUSIONS: An ICA approach to
      LRHC results in shorter hospital stay and decreased rates of clinical ileus.

PMID- 29587967
TI  - The gluteal muscles in end-stage osteoarthritis of the hip: intra- and
      interobserver reliability and agreement of MRI assessments of muscle atrophy and
      fatty degeneration.
AB  - AIM: To assess the intra- and interobserver reliability and agreement of muscular
      atrophy and fatty degeneration of the gluteal muscles on magnetic resonance
      imaging (MRI) in patients with end-stage osteoarthritis of the hip. MATERIALS AND
      METHODS: Thirty-nine patients with end-stage osteoarthritis of the hip, who
      scheduled for hip replacement surgery, were included in the study. The cross
      sectional areas of the gluteus medius and minimus muscles were manually
      circumscribed and automatically calculated, while intramuscular fatty
      degeneration was assessed using the semi-quantitative classification system of
      Goutallier. Two independent observers performed all the evaluations. RESULTS:
      Good agreement and excellent reliability were found for the cross-sectional areas
      of the gluteus medius and gluteus minimus (intraclass correlation coefficient
      [ICC] for intra-observer 0.97 and 0.93, ICC for interobserver 0.98 and 0.95).
      Fair reliability was found for fatty degeneration of the gluteus muscles (mean
      kappa 0.23 and mean prevalence-adjusted kappa 0.53). The average proportion of
      agreement for the raters was 0.71. CONCLUSION: The present study demonstrated
      substantial agreement and excellent intra- and interobserver reliability for the
      measurements of the cross-sectional areas of the gluteus medius and gluteus
      minimus. Assessment of fatty degeneration had fair intra- and interobserver
      reliability, but acceptable agreement.

PMID- 29587968
TI  - Phakic intraocular lenses: Where are we now?

PMID- 29587969
TI  - Femtosecond laser-assisted cataract surgery in eyes with foldable anterior or
      posterior chamber phakic intraocular lenses.
AB  - We describe a technique for the application of femtosecond laser-assisted
      cataract surgery in eyes with cataract and previous implantation of a foldable
      anterior or posterior chamber phakic intraocular lens (pIOL). In 2 eyes with an
      anterior chamber pIOL (angle-supported Acrysof Cachet) and 3 eyes with a
      posterior chamber pIOL (2 eyes with an Implantable Collamer Lens pIOL; 1 eye with
      a Phakic Refractive Lens), a femtosecond laser was used to create a capsulotomy,
      perform lens fragmentation, and create corneal incisions with the pIOL in situ.
      In all cases, the capsulotomy was created successfully. Lens fragmentation was
      complete in 4 eyes and incomplete in 1 eye, where trapped cavitation bubbles in
      the space between the posterior chamber pIOL and anterior lens capsule were
      evident as a result of a shallow vault of the pIOL.

PMID- 29587970
TI  - Association between cataract progression and ischemia-modified albumin in
      relation to oxidant-antioxidant profiles in the serum, aqueous humor, and lens.
AB  - PURPOSE: To evaluate the levels of ischemia-modified albumin (IMA) in relation to
      oxidant-antioxidant profiles in the serum, aqueous, and lens in cataract
      patients. SETTING: Department of Ophthalmology, Menoufia University, Shebin El
      Kom, Menoufia, Egypt. DESIGN: Prospective case series. METHODS: Patients were
      divided into 2 groups. The cataract (study) group comprised patients with senile
      cataract and the control group, age- and sex-matched healthy persons. Patients
      with systemic disease or cataract formation secondary to identifiable causes were
      excluded. In all cases, a complete history was taken and a clinical examination
      was performed. In the cataract group, the lens was examined, and the cataract
      type and severity were graded. Blood levels of catalase, malondialdehyde (MDA),
      superoxide dismutase (SOD), and IMA were measured in all participants and in the
      aqueous and lens lysate of cataract patients. RESULTS: Each group comprised 30
      participants. Cataract patients had significant higher levels of serum MDA and
      IMA than the control group but had lower levels of serum catalase and SOD.
      Patients with cortical cataracts had higher level of serum IMA, aqueous catalase,
      and SOD levels patients with nuclear cataracts but had a lower level of lens SOD.
      There was a significant positive correlation between serum MDA and the patient's
      age and serum catalase levels. CONCLUSION: Patients with cortical cataract had
      increased local oxidative stress and diminished antioxidant activity compared
      with systemic oxidative activity, which was not the same in patients with nuclear
      cataract.

PMID- 29587971
TI  - Prevalence of meibomian gland dysfunction at the time of cataract surgery.
AB  - PURPOSE: To determine the incidence of meibomian gland dysfunction and quantify
      subjective dry-eye symptoms in cataract surgery candidates. SETTING: Brest
      University Hospital, Brest, France. DESIGN: Prospective case series. METHODS:
      Patients having cataract surgery between November 2015 and June 2016 completed
      the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Lipid layer
      thickness and partial blink rate measurements as well as gland structure
      assessment were performed using the Lipiview Ocular Surface Interferometer. A
      slitlamp examination determined tear breakup time; the quantity and quality of
      the meibomian gland secretion were determined using the Meibomian Gland
      Evaluator. RESULTS: The study comprised 342 eyes of 180 patients. The mean lipid
      layer thickness was 72.5 nm +/- 19.91 (SD). In patients with a SPEED score lower
      than 8, the mean lipid layer thickness was 77.5 +/- 19.48 nm. In patients with a
      SPEED score of 8 or higher, the mean lipid layer thickness was 58.5 +/- 19.58 nm.
      The difference in lipid layer thickness between SPEED score groups was
      statistically significant (P < .05). Fifty-two percent of patients had meibomian
      gland dysfunction, and 56% had meibomian gland atrophy equal to or more than
      Arita grade 1. Meibomian gland function correlated significantly with lipid layer
      thickness, symptoms, age, and gland atrophy (P < .05). CONCLUSIONS: The incidence
      of meibomian gland dysfunction was high in patients presenting for cataract
      surgery. Fifty percent of patients with meibomian gland dysfunction were
      asymptomatic. Correct criteria and meibomian function and structure assessment
      are critical to diagnosis. Comprehensive preoperative testing should routinely
      include evaluation of meibomian function.

PMID- 29587972
TI  - Comparative analysis of visual outcomes with 4 intraocular lenses: Monofocal,
      multifocal, and extended range of vision.
AB  - PURPOSE: To compare the visual acuity, refractive outcomes, and quality of vision
      in patients with bilateral implantation of 4 intraocular lenses (IOLs). SETTINGS:
      Department of Neurosciences, Biomedicine and Movement Sciences, Eye Clinic,
      University of Verona, Verona, and Carones Ophthalmology Center, Milano, Italy.
      DESIGN: Prospective case series. METHODS: The study included patients who had
      bilateral cataract surgery with the implantation of 1 of 4 IOLs as follows:
      Tecnis 1-piece monofocal (monofocal IOL), Tecnis Symfony extended range of vision
      (extended-range-of-vision IOL), Restor +2.5 diopter (D) (+2.5 D multifocal IOL),
      and Restor +3.0 D (+3.0 D multifocal IOL). Visual acuity, refractive outcome,
      defocus curve, objective optical quality, contrast sensitivity, spectacle
      independence, and glare perception were evaluated 6 months after surgery.
      RESULTS: The study comprised 185 patients. The extended-range-of-vision IOL (55
      patients) showed better distance visual outcomes than the monofocal IOL (30
      patients) and high-addition apodized diffractive-refractive multifocal IOLs (P <=
      .002). The +3.0 D multifocal IOL (50 patients) showed the best near visual
      outcomes (P < .001). The +2.5 D multifocal IOL (50 patients) and extended-range
      of-vision IOL provided significantly better intermediate visual outcomes than the
      other 2 IOLs, with significantly better vision for a defocus level of -1.5 D (P <
      .001). Better spectacle independence was shown for the +2.5 D multifocal IOL and
      extended-range-of-vision IOL (P < .001). CONCLUSIONS: The extended-range-of
      vision IOL and +2.5 D multifocal IOL provided significantly better intermediate
      visual restoration after cataract surgery than the monofocal IOL and +3.0 D
      multifocal IOL, with significantly better quality of vision with the extended
      range-of-vision IOL.

PMID- 29587973
TI  - Improved utilization of operating room time for trainee cataract surgery in a
      public hospital setting.
AB  - PURPOSE: To examine the effect of group goal and group performance theories on
      operating room efficiency in resident-performed cataract surgery. SETTING:
      Zuckerberg San Francisco General Hospital and Trauma Center, Department of
      Ophthalmology, University of California, San Francisco, California, USA. DESIGN:
      Prospective case series. METHODS: This study assessed 4 specific segments of
      operating room utilization identified as room-to-incision time, incision-to-close
      time, close-to-exit time, and room turnover time. The time segments were measured
      for resident-performed cataract cases before the proposed intervention. Then,
      group goals were set for ideal times of each utilization segment. Behaviors of
      the surgery, anesthesia, nursing, pharmacy, and housekeeping teams that would
      improve group performance were identified. Utilization segments were measured
      again after the intervention. RESULTS: The time segments were measured for 134
      resident-performed cataract cases before the proposed intervention and again
      after the intervention for 136 resident-performed cataract cases. Before the
      intervention, the mean overall case time was 55 minutes, allowing for 10 cases in
      a 10-hour day. After the intervention, the mean overall case time was 46 minutes,
      allowing for 13 cases in a 10-hour day. The decrease in postintervention times
      for overall case time, room-to-incision time, and close-to-exit time were
      statistically significant. CONCLUSIONS: Operating room utilization for resident
      performed cataract surgery was enhanced by setting group goals. A
      multidisciplinary effort to enhance group performance through behavior
      modification can be implemented immediately and improve efficiency without
      compromising patient safety or resident teaching.

PMID- 29587974
TI  - Macular photostress and visual experience between microscope and intracameral
      illumination during cataract surgery.
AB  - PURPOSE: To evaluate macular photostress and visual experience between coaxial
      microscope illumination versus oblique intracameral illumination during cataract
      surgery. SETTING: Gachon University Gil Hospital, Incheon, South Korea. DESIGN:
      Prospective case series. METHODS: Consecutive patients who had cataract surgery
      using microscope illumination and intracameral illumination were included. The
      patients were asked to complete a questionnaire (seeing strong lights, feeling
      photophobia, feeling startled (fright) when seeing lights, seeing any colors,
      seeing any instruments or surgical procedures, and estimating intraoperative
      visual function) designed to describe their cataract surgery experience. The
      images projected on the retina of the model eye (rear view) with artificial
      opaque fragments in the anterior chamber during simulating cataract surgery were
      compared between the 2 illumination types. RESULTS: Sixty patients completed the
      questionnaire. Scores for strong lights, photophobia, fright, and color
      perception were significantly higher with microscope illumination than with
      intracameral illumination (all P < .001). More patients preferred the
      intracameral illumination (45 [75.0%]) to the microscope illumination (13
      [21.7%]). In the rear-view images created in a model eye, only the bright
      microscope light in the center was seen without any lens image in the microscope
      illumination. However, in the intracameral illumination, the less bright light
      from the light pipe in the periphery and the lens fragments were seen more
      clearly. CONCLUSIONS: In a view of the patients' visual experience, oblique
      intracameral illumination caused less subjective photostress and was preferred
      over coaxial microscope illumination. Objective findings from the model-eye
      experiment correlated to the result of visual experience.

PMID- 29587975
TI  - Astigmatic correction by intrastromal astigmatic keratotomy during femtosecond
      laser-assisted cataract surgery: Factors in outcomes.
AB  - PURPOSE: To evaluate the 6-month outcomes of femtosecond laser astigmatic
      keratotomy (AK) combined with femtosecond laser-assisted cataract surgery and
      identify factors affecting the efficacy of astigmatic correction. SETTING: Seoul
      St. Mary's Hospital, Catholic University of Korea, Seoul, South Korea. DESIGN:
      Retrospective case series. METHODS: Femtosecond laser AK was performed during
      femtosecond laser-assisted cataract surgery. The keratometric astigmatism,
      refractive cylinder, corneal hysteresis (CH), and corneal resistance factor (CRF)
      were measured preoperatively and postoperatively at 1 week, 2 months, and 6
      months. Vector analysis to evaluate the 6-month outcomes of femtosecond laser AK
      and univariable regression analysis to determine the factors influencing the
      correction index were performed. RESULTS: The study enrolled 89 eyes of 89
      patients. The stigmatism type, CH, CRF, and absolute angle of error showed
      significant correlations with the correction index (P = .041, P = .029, P = .044,
      and P < .001, respectively). There was a significant difference in the correction
      index and no difference in keratometric astigmatism between with-the-rule (WTR),
      against-the-rule (ATR), and oblique astigmatism (P = .044). The keratometric
      astigmatism with ATR and oblique astigmatism (0.66 diopter [D] +/- 0.42 [SD] and
      0.46 +/- 0.27 D, respectively) was significantly lower than the refractive
      cylinder (0.92 +/- 0.56 D and 0.78 +/- 0.43 D, respectively) (P < .05); this was
      not the case for WTR astigmatism. CONCLUSIONS: The efficacy of femtosecond laser
      AK was affected by the biomechanical properties of the cornea and astigmatism
      type. Further studies incorporating the individual biomechanical properties of
      the cornea and total corneal astigmatism in a nomogram are recommended.

PMID- 29587976
TI  - Effect of supplementary implantation of a sulcus-fixated intraocular lens in
      patients with negative dysphotopsia.
AB  - PURPOSE: To evaluate whether the outcome of negative dysphotopsia treatment by
      implantation of a Sulcoflex intraocular lens (IOL) can be understood using
      individual biometry and optical modeling data. SETTING: University Eye Clinic,
      Maastricht University Medical Centre, Maastricht, the Netherlands. DESIGN:
      Retrospective case series. METHODS: Patients with negative dysphotopsia were
      treated with supplementary implantation of a sulcus-fixated IOL. Preoperative and
      postoperative ray-tracing optical models of eyes with negative dysphotopsia were
      constructed in the Zemax Optic Studio program using individual biometric data.
      The relationship between biometric parameters, ray-tracing data, and the course
      of negative dysphotopsia was evaluated. RESULTS: The study comprised 8 patients
      (10 eyes). After surgery, negative dysphotopsia resolved completely in 6 eyes,
      partially in 2 eyes, and persisted in 2 eyes. There was no relationship between
      the course of negative dysphotopsia and age, IOL power, or individual biometry
      results other than a larger angle kappa that was observed in 2 patients with
      persistent negative dysphotopsia after surgery. Preoperative ray-tracing models
      showed a decrease in light irradiance at the periphery relative to the center of
      visual field. After sulcus-fixated IOL implantation, this decrease partially
      resolved, in particular, for a small pupil aperture (P < .05), and it was more
      prominent in patients in whom negative dysphotopsia resolved completely than in
      those with partial or persistent negative dysphotopsia (P = .065 at 1.5 mm
      aperture). CONCLUSIONS: Of all individual biometry results, only angle kappa
      showed a relationship with the course of negative dysphotopsia. In patient
      specific optical modeling of sulcus-fixated IOL implantation, the increase in
      simulated light irradiance at the periphery was related to the course of negative
      dysphotopsia.

PMID- 29587977
TI  - Influence of surface light scattering and glistenings of intraocular lenses on
      visual function 15 to 20 years after surgery.
AB  - PURPOSE: To assess the long-term influence of surface light scattering and
      glistenings of hydrophobic acrylic (Acrysof), silicone, and poly(methyl
      methacrylate) (PMMA) intraocular lenses (IOLs) on visual function. SETTING:
      Eleven surgical sites, Japan. DESIGN: Retrospective case series. METHODS:
      Patients who had cataract surgery with implantation of a hydrophobic acrylic,
      silicone, or PMMA IOL from 1994 to 2000 were examined. Silicone and PMMA IOLs
      were not restricted to specific manufacturers or models. Patients were included
      if their corrected distance visual acuity (CDVA) within 3 months postoperatively
      (baseline CDVA) was 20/25 or better. The CDVA, contrast sensitivity, degree of
      surface light scattering measured with Pentacam densitometry, and glistening
      grades were recorded at the patient's latest visit. RESULTS: Of the eyes, 31 had
      a hydrophobic acrylic IOL, 37 a silicone IOL, and 30 a PMMA IOL. Surface light
      scattering and glistenings were significantly greater with the hydrophobic
      acrylic IOL than with silicone and PMMA IOLs (P < .0001). The CDVA at the latest
      visit as well as the changes in CDVA from the baseline to the latest visit did
      not differ between the IOLs and was unaffected by surface light scattering and
      glistenings, as was the contrast sensitivity. CONCLUSIONS: The hydrophobic
      acrylic IOL was associated with a significantly greater level of surface light
      scattering and glistenings than the silicone IOLs and PMMA IOLs 15 to 20 years
      postoperatively. However, the optical phenomena within the optics of the
      hydrophobic acrylic IOL did not influence the patients' visual function.

PMID- 29587978
TI  - Mechanical model of human eye compliance for volumetric occlusion break surge
      measurements.
AB  - PURPOSE: To develop a mechanical model of human eye compliance for volumetric
      studies. SETTING: Alcon Research, Ltd., Lake Forest, California, USA. DESIGN:
      Experimental study. METHODS: Enucleated human eyes underwent pressurization and
      depressurization cycles with peak intraocular pressures (IOPs) of 60 to 100 mm
      Hg; anterior chamber pressure and volume changes were measured. Average net
      volume change curves were calculated as a function of IOP for each eye. Overall
      mean volumes were computed from each eye's average results at pressure points
      extrapolated over the range of 5 to 90 mm Hg. A 2-term exponential function was
      fit to these results. A fluid chamber with a displaceable piston was created as a
      mechanical model of this equation. A laser confocal displacement meter was used
      to measure piston displacement. A test bed incorporated the mechanical model with
      a mounted phacoemulsification probe and allowed for simulated occlusion breaks.
      Surge volume was calculated from piston displacement. RESULTS: An exponential
      function, V = C1 * exp(C2 * IOP) + C3 * exp(C4 * IOP) - V0, where V, the volume,
      was fit to the final depressurization curve obtained from 15 enucleated human
      eyes. The C1 through C4 values were -0.07141, -0.23055, -0.14972, and -0.02006,
      respectively. The equation was modeled using a piston system with 3 parallel
      springs that engaged serially. The mechanical model mimicked depressurization
      curves observed in human cadaver eyes. CONCLUSION: The resulting mechanical
      compliance model measured ocular volumetric changes and thus would be helpful in
      characterizing the postocclusion break surge response.

PMID- 29587979
TI  - Keratophakia with autograft aided by a femtosecond laser: One-year follow-up.
AB  - Autologous tissue from correction of myopia with small-incision lenticule
      extraction in 1 eye of a patient was used to enhance corneal curvature in the
      contralateral eye, in which a corneal ulcer had flattened the cornea.
      Regularization of the corneal tomography was achieved, improving the visual
      quality and visual capacity of the patient.

PMID- 29587980
TI  - February consultation #2.

PMID- 29587981
TI  - Negative dysphotopsia and dyschromatopsia: February consultation #1.

PMID- 29587982
TI  - February consultation #3.

PMID- 29587983
TI  - February consultation #4.

PMID- 29587984
TI  - February consultation #5.

PMID- 29587985
TI  - February consultation #7.

PMID- 29587986
TI  - February consultation #6.

PMID- 29587987
TI  - February consultation #8.

PMID- 29587988
TI  - February consultation #9.

PMID- 29587989
TI  - Editor's Comment.

PMID- 29587990
TI  - Reply.

PMID- 29587991
TI  - Difference between capsule tensile strength and capsulotomy edge strength.

PMID- 29587992
TI  - Erratum.

PMID- 29587993
TI  - Blood pressure.

PMID- 29587996
TI  - Constructional Apraxia.

PMID- 29587997
TI  - Hologenome theory and the honey bee pathosphere.
AB  - Recent research has provided improved genome-level views of diversity across
      global honey bee populations, the gut microbiota residing within them, and the
      expanding pathosphere challenging honey bees. Different combinations of
      bee/microbiota/pathosphere genome complexes may explain regional variation in
      apiculture productivity and mortality. To understand this, we must consider
      management and research approaches in light of a hologenome paradigm: that honey
      bee fitness is determined by the composite bee and microbiota genomes. Only by
      considering the hologenome can we truly interpret and address impacts from the
      pathosphere, pesticides, toxins, nutrition, climate and other stressors affecting
      bee health.

PMID- 29587998
TI  - Causes of variation in wild bee responses to anthropogenic drivers.
AB  - Anthropogenic change can have large impacts on wild bees and the pollination
      services they provide. However, the overall pattern of wild bee response to
      drivers such as land-use change, pesticides, pathogens, and climate change has
      been one of variability in both the magnitude and directionality of responses. We
      argue that two causes contribute to this variation. First, different species
      exhibit differential responses to the same anthropogenic drivers. Second, these
      anthropogenic drivers vary in type and magnitude that will drive variation in bee
      responses. For this second issue, we focus on land-use change, the most well
      studied driver. We conclude by discussing how understanding species-level
      responses and the magnitude of land-use change can make bee conservation more
      effective.

PMID- 29587999
TI  - From puddles to planet: modeling approaches to vector-borne diseases at varying
      resolution and scale.
AB  - Since the original Ross-Macdonald formulations of vector-borne disease
      transmission, there has been a broad proliferation of mathematical models of
      vector-borne disease, but many of these models retain most to all of the
      simplifying assumptions of the original formulations. Recently, there has been a
      new expansion of mathematical frameworks that contain explicit representations of
      the vector life cycle including aquatic stages, multiple vector species, host
      heterogeneity in biting rate, realistic vector feeding behavior, and spatial
      heterogeneity. In particular, there are now multiple frameworks for spatially
      explicit dynamics with movements of vector, host, or both. These frameworks are
      flexible and powerful, but require additional data to take advantage of these
      features. For a given question posed, utilizing a range of models with varying
      complexity and assumptions can provide a deeper understanding of the answers
      derived from models.

PMID- 29588000
TI  - Bee nutrition and floral resource restoration.
AB  - Bee-population declines are linked to nutritional shortages caused by land-use
      intensification, which reduces diversity and abundance of host-plant species.
      Bees require nectar and pollen floral resources that provide necessary
      carbohydrates, proteins, lipids, and micronutrients for survival, reproduction,
      and resilience to stress. However, nectar and pollen nutritional quality varies
      widely among host-plant species, which in turn influences how bees forage to
      obtain their nutritionally appropriate diets. Unfortunately, we know little about
      the nutritional requirements of different bee species. Research must be conducted
      on bee species nutritional needs and host-plant species resource quality to
      develop diverse and nutritionally balanced plant communities. Restoring
      appropriate suites of plant species to landscapes can support diverse bee species
      populations and their associated pollination ecosystem services.

PMID- 29588001
TI  - Insect-pathogen interactions: contribution of viral adaptation to the emergence
      of vector-borne diseases, the example of chikungunya.
AB  - The emergence or re-emergence of vector borne diseases represents a major public
      health problem. In general, therapeutic or prophylactic treatments along with
      vaccines are missing or inefficient, emphasizing the need for increased control
      of vector populations. Understanding the interactions of human pathogens with
      their insect vectors will aid us in our understanding of viral emergence and the
      dynamics of these events. Chikungunya virus (CHIKV) is a mosquito-borne virus
      that typically causes incapacitating arthralgia, rash, and fever. It is mainly
      transmitted by Aedes aegypti and secondarily by Aedes albopictus. Since its
      emergence in 2004, CHIKV has continued to spread globally due in large part to an
      enhanced transmission of the virus by the vector Ae. albopictus. Ae. albopictus
      adaptive mutations modulated by epistatic interactions have modified CHIKV
      transmission and thus the global spread and dynamics of this disease.

PMID- 29588002
TI  - Pesticides and pollinators: a context-sensitive policy approach.
AB  - I examine recent policymaking efforts in the United States (US) that seek to
      improve how risks posed by pesticides to insect pollinators are assessed and
      managed. Utilizing the case of ongoing honey bee die-offs, I argue for a context
      sensitive policy framework. From a scientific perspective, this entails not
      ignoring the uncertain knowledge emerging from laboratory and field studies
      regarding the indirect effects of low levels of certain insecticides in
      combination with other factors. From a social scientific perspective, policy
      initiatives to build partnerships between growers and beekeepers toward
      mitigating exposure to pesticides are crucial, and need to acknowledge barriers
      to the adoption of best management practices as well as a historically
      established asymmetry between growers and beekeepers in the pollination industry.

PMID- 29588003
TI  - Back to the future: the sterile insect technique against mosquito disease
      vectors.
AB  - With the global burden of mosquito-borne diseases increasing, and some
      conventional vector control tools losing effectiveness, the sterile insect
      technique (SIT) is a potential new tool in the arsenal. Equipment and protocols
      have been developed and validated for efficient mass-rearing, irradiation and
      release of Aedines and Anophelines that could be useful for several control
      approaches. Assessment of male quality is becoming more sophisticated, and
      several groups are well advanced in pilot site selection and population
      surveillance. It will not be long before SIT feasibility has been evaluated in
      various settings. Until perfect sexing mechanisms exist, combination of Wolbachia
      induced phenotypes, such as cytoplasmic incompatibility and pathogen
      interference, and irradiation may prove to be the safest solution for population
      suppression.

PMID- 29588004
TI  - Improving the future of honey bee breeding programs by employing recent
      scientific advances.
AB  - A recent abundance of studies investigating causes of honey bee (Apis mellifera)
      colony losses has led to enhanced recommendations in management practices with
      particular emphasis on breeding for resistant bee stocks. Here we review the
      latest advances in research which could improve the future of breeding programs.
      We discuss diversity in colonies particularly in breeding programs, giving
      special emphasis to recent improvement in cryopreservation of honey bee
      germplasm. We also review factors that affect the health and reproductive quality
      of queens and drones. We briefly discuss how techniques developed by scientists
      are finding more regular usage with breeders in the assessment of reproductive
      caste health and quality and in determining best management practices for
      breeding programs.

PMID- 29588005
TI  - Nutrition, immunity and viral infections in honey bees.
AB  - Viruses and other pathogens can spread rapidly in social insect colonies from
      close contacts among nestmates, food sharing and periods of confinement. Here we
      discuss how honey bees decrease the risk of disease outbreaks by a combination of
      behaviors (social immunity) and individual immune function. There is a
      relationship between the effectiveness of social and individual immunity and the
      nutritional state of the colony. Parasitic Varroa mites undermine the
      relationship because they reduce nutrient levels, suppress individual immune
      function and transmit viruses. Future research directions to better understand
      the dynamics of the nutrition-immunity relationship based on levels of stress,
      time of year and colony demographics are discussed.

PMID- 29588006
TI  - Effects of genotype, environment, and their interactions on honey bee health in
      Europe.
AB  - There are several reports of honey bee populations in Europe which survive
      without treatment for Varroa. However, when evaluated outside their native area,
      higher survival and resistance traits were not observed in colonies of a survivor
      population. Varroa infestation is strongly influenced by environmental factors,
      probably affecting threshold levels on a European scale. In a Europe-wide
      experiment colonies of local origin survived significantly longer than colonies
      of non-local origin, clearly indicating the presence of genotype-environment
      interactions. Transmission by Varroa selects for virulent strains of DWV, but it
      is currently unknown how these may interact with different genotypes of bees. The
      distribution of Nosema ceranae is significantly affected by environment, but
      there is at least one Nosema-resistant population.

PMID- 29588007
TI  - Overwintering honey bees: biology and management.
AB  - In temperate climates, honey bees (Apis mellifera) survive the winter by entering
      a distinct physiological and behavioral state. In recent years, beekeepers are
      reporting unsustainably high colony losses during the winter, which have been
      linked to parasitization by Varroa mites, virus infections, geographic location,
      and variation across honey bee genotypes. Here, we review literature on
      environmental, physiological, and social factors regulating entrance,
      maintenance, and exit from the overwintering state in honey bees in temperate
      regions and develop a testable model to explain how multiple factors may be
      acting synergistically to regulate this complex transition. We also review
      existing knowledge of the factors affecting overwintering survival in honey bees
      and providing suggestions to beekeepers aiming to improve their colonies'
      overwintering success.

PMID- 29588008
TI  - Effects of 'inactive' ingredients on bees.
AB  - Honey bees are sensitive to widespread co-formulants used in agrochemicals, and
      evaluation of the role of these 'inerts or inactives' in pollinator decline is
      only in its formative stages. Lack of disclosure of formulation ingredients in
      major products and lack of adequate methods for their analysis constrain the
      assessment of total chemical load and agrochemical exposures on bees. Most
      studies to document pesticide effects on honey bees are performed without the
      formulation or other relevant spray adjuvant components used to environmentally
      apply the toxicant. Formulations are generally more toxic than active
      ingredients, particularly fungicides, by up to 26,000-fold based on published
      literature. Some 'inactive' candidates for future risk assessment for pollinators
      include the organosilicone surfactants and the co-solvent N-methyl-2-pyrrolidone.

PMID- 29588009
TI  - Editorial overview: Vectors and medical and veterinary entomology: From molecular
      biology to field ecology.

PMID- 29588010
TI  - Integrated pest and pollinator management-adding a new dimension to an accepted
      paradigm.
AB  - In this chapter we argue that while pesticides can be harmful to pollinators,
      when they are used in an integrated pest and pollinator management (IPPM)
      context, both pest management and pollinator protection may be achieved. Our
      growing knowledge of the impacts of pesticides on honey bees as well as bumble
      bees and solitary bees allows us to use the latitude we have in pest management
      including non-pesticidal pest management practices, changing pesticide types and
      incorporating other, less susceptible pollinator species into commercial
      practice. Pollinator health should be a central component of integrated pest
      management research, education and extension to produce viable IPPM approaches.

PMID- 29588011
TI  - Molecular pathogenesis of American Foulbrood: how Paenibacillus larvae kills
      honey bee larvae.
AB  - American Foulbrood caused by Paenibacillus larvae is one of the unsolved health
      problems honey bee colonies are suffering from. In the recent past, considerable
      progress has been achieved in understanding molecular details of P. larvae
      infections of honey bee larvae. This was facilitated by the development of
      molecular tools for manipulating P. larvae and by the availability of complete
      genome sequences of different P. larvae genotypes. We here report on several
      peptides and proteins that have recently been identified, biochemically analyzed,
      and proposed to act as virulence factors of P. larvae. For some of them,
      experimental proof for their role as virulence factor has been provided allowing
      presenting a preliminary model for the molecular pathogenesis of American
      Foulbrood.

PMID- 29588012
TI  - Honey bee surveillance: a tool for understanding and improving honey bee health.
AB  - Honey bee surveillance systems are increasingly used to characterize honey bee
      health and disease burdens of bees in different regions and/or over time. In
      addition to quantifying disease prevalence, surveillance systems can identify
      risk factors associated with colony morbidity and mortality. Surveillance systems
      are often observational, and prove particularly useful when searching for risk
      factors in real world complex systems. We review recent examples of surveillance
      systems with particular emphasis on how these efforts have helped increase our
      understanding of honey bee health.

PMID- 29588013
TI  - Death of the bee hive: understanding the failure of an insect society.
AB  - Since 2007 honey bee colony failure rates overwinter have averaged about 30%
      across much of North America. In addition, cases of extremely rapid colony
      failure have been reported, which has been termed colony collapse disorder. Both
      phenomena result from an increase in the frequency and intensity of chronic
      diseases and environmental stressors. Colonies are often challenged by multiple
      stressors, which can interact: for example, pesticides can enhance disease
      transmission in colonies. Colonies may be particularly vulnerable to sublethal
      effects of pathogens and pesticides since colony functions are compromised
      whether a stressor kills workers, or causes them to fail at foraging. Modelling
      provides a way to understand the processes of colony failure by relating impacts
      of stressors to colony-level functions.

PMID- 29588014
TI  - Xenobiotic detoxification pathways in honey bees.
AB  - Relative to most other insect genomes, the western honey bee Apis mellifera has a
      deficit of detoxification genes spanning Phase I (functionalization), II
      (conjugation) and III (excretion) gene families. Although honeybees do not
      display across-the-board greater sensitivity to pesticides, this deficit may
      render them vulnerable to synergistic interactions among xenobiotics. Diet
      quality, in terms of protein and phytochemical content, has a pronounced
      influence on tolerance of toxic compounds. Detoxification gene inventory
      reduction may reflect an evolutionary history of consuming relatively chemically
      benign nectar and pollen, as other apoid pollinators display comparable levels of
      cytochrome P450 gene reduction. Enzymatic detoxification in the eusocial A.
      mellifera may be complemented by behaviors comprising a 'social detoxification
      system,' including forager discrimination, dilution by pollen mixing, and colony
      food processing via microbial fermentation, that reduces the number or quantity
      of ingested chemicals requiring detoxification.

PMID- 29588015
TI  - Connecting genotypes to medically relevant phenotypes in major vector mosquitoes.
AB  - Transmission of mosquito-borne human disease relies on vectors maintaining strong
      human host preference and continued susceptibility to disease-causing pathogens
      or parasites. These traits are affected by the genetics and the environments of
      all involved organisms, and genotypic interactions are common between parasite
      and vector, and between virus and vector. A recent study on Aedes host preference
      has exploited natural genetic variation to make great progress. Here I review our
      current understanding of the genetic basis of transmission-relevant traits in
      Anopheles and Aedes, highlighting additional research areas that would benefit
      from the integration of natural genetic variation.

PMID- 29588016
TI  - Chalkbrood: epidemiological perspectives from the host-parasite relationship.
AB  - Chalkbrood is a fungal brood disease of the honey bee, Apis mellifera, caused by
      the parasite Ascosphaera apis. Considered as a stress-related disease, the
      severity of chalkbrood outbreaks depend on a multitude of interacting factors.
      The specific relationship between host and parasite in this disease is
      interesting because the parasite is both heterothallic and semelparous. Recent
      studies highlight that this specific host-parasite relationship is influenced by
      factors such as interactions with other parasite strains or species, and
      environmental perturbations. To understand how to protect pollinators most
      effectively, it is crucial that future research takes a more ecologically
      relevant approach by studying the basic biology of the host-parasite relationship
      in the context of the multi-factorial processes that influence it.

PMID- 29588017
TI  - Intersections between neonicotinoid seed treatments and honey bees.
AB  - A growing understanding of the often subtle unintended impacts of neonicotinoid
      seed treatments on both non-target organisms and their environment have led to
      concerns about the suitability of current pest management approaches in large
      scale agriculture. Several neonicotinoid compounds are used in seed treatments of
      the most widely grown grain and oilseed crops worldwide. Most applications are
      made prophylactically and without prior knowledge of pest populations. A growing
      body of evidence suggests that these compounds become contaminants of soil,
      water, and plant products, including pollen and nectar. These unforeseen routes
      of exposure are documented to have negative impacts on honey bee health and also
      have potential to exert effects on a broader environmental scale.

PMID- 29588018
TI  - Chemical ecology and olfaction in arthropod vectors of diseases.
AB  - Hematophagous arthropods (ticks and insects, collectively hereafter referred to
      as vectors) transmit various life threatening diseases resulting in over one
      million human deaths annually. Exploiting vertebrates for blood demanded
      extensive sensory and behavioral adaptations that are apparent across the
      evolutionary range of vector species, from primitive ticks to advanced dipterans.
      Since animal senses are biological features that have been shaped by natural
      selection to promote adaptive behavior, a variety of exciting patterns are
      apparent in what they sense and how. Vectors display robust olfactory driven
      behaviors. A distinct yet limited range of volatile organic compounds are
      parsimoniously used as major cues for tracking in various contexts. These
      chemicals elicit behaviors such as attraction or repulsion/avoidance while
      vectors seek habitats, hosts, mates, or oviposition sites. Interestingly, there
      is a substantial consilience among olfactory structures and function in arthropod
      vectors, which is also reflected in the parsimonious use of chemical ligands. A
      detailed analysis of chemosensory signals and reception by these arthropod
      vectors can be exploited to identify natural ligands that can be used as baits to
      manipulate vector behaviors.

PMID- 29588019
TI  - Genetic technologies for disease vectors.
AB  - The first genetic technologies for insect vectors of disease were introduced 20
      years ago. As of today there are 12 classes of genetic technologies used as
      functional genomic tools for insect vectors of important diseases. Although the
      applications of genetic technologies in insect disease vectors have been
      conducted primarily in mosquitoes, other insect systems could benefit from
      current technologies. While the various technological platforms are likely to
      function in diverse arthropods, the delivery of these technologies to cells and
      tissues of interest is the major technical constraint that limits their
      widespread adoption. Increased community resources of various types would enhance
      the adoption of these technologies and potentially eliminate technical
      limitations.

PMID- 29588020
TI  - Impact of insect salivary proteins in blood feeding, host immunity, disease, and
      in the development of biomarkers for vector exposure.
AB  - Functional genomic approaches based on expression of recombinant proteins linked
      to biochemical and disease model approaches resulted in the discovery of novel
      biological activities and the role some of these proteins play in disease
      transmission. Importantly, the expression of salivary proteins was recently shown
      to be affected by environmental factors and by the presence of the pathogen in
      the salivary gland. A practical application resulting from insect saliva research
      is the use of insect antigenic salivary protein as biomarkers of vector exposure
      in humans and animal reservoirs, an approach that is yielding interesting results
      in the field.

PMID- 29588021
TI  - Editorial Overview: Social insects: From the lab to the landscape - translational
      approaches to pollinator health.

PMID- 29588022
TI  - Use of whole body vibration in individuals with chronic stroke: Transmissibility
      and signal purity.
AB  - This study examined (1) the influence of whole body vibration (WBV) frequency (20
      Hz, 30 Hz, 40 Hz), amplitude (low: 0.8 mm and high: 1.5 mm) and body postures
      (high-squat, deep-squat, tip-toe standing) on WBV transmissibility and signal
      purity, and (2) the relationship between stroke motor impairment and WBV
      transmissibility/signal purity. Thirty-four participants with chronic stroke were
      tested under 18 different conditions with unique combinations of WBV frequency,
      amplitude, and body posture. Lower limb motor function and muscle spasticity were
      assessed using the Fugl-Meyer Assessment and Modified Ashworth Scale
      respectively. Nine tri-axial accelerometers were used to measure acceleration at
      the WBV platform, and the head, third lumbar vertebra, and bilateral hips, knees,
      and ankles. The results indicated that WBV amplitude, frequency, body postures
      and their interactions significantly influenced the vibration transmissibility
      and signal purity among people with chronic stroke. In all anatomical landmarks
      except the ankle, the transmissibility decreased with increased frequency,
      increased amplitude or increased knee flexion angle. The transmissibility was
      similar between the paretic and non-paretic side, except at the ankle during tip
      toe standing. Less severe lower limb motor impairment was associated with greater
      transmissibility at the paretic ankle, knee and hip in certain WBV conditions.
      Leg muscle spasticity was not significantly related to WBV transmissibility. In
      clinical practice, WBV amplitude, frequency, body postures need to be considered
      regarding the therapeutic purpose. Good contact between the feet and vibration
      platform and symmetrical body-weight distribution pattern should be ensured.

PMID- 29588023
TI  - Managing soft tissues in severe lower limb trauma in an ageing population.
AB  - PURPOSE: With an ageing population, the incidence of trauma in those aged over 65
      years is increasing. Strategies for dealing with these patients must be
      developed. At present the standard management of open tibial fractures in the UK
      is described by the BOAST4 guidelines (from the British Orthopaedic Association
      and British Association of Plastic & Aesthetic Surgeons). It is not clear to what
      extent these are appropriate for older patients. We describe our experience of
      managing elderly patients presenting with open tibial fractures. METHOD: Patients
      were identified via prospectively collected national and departmental databases.
      These data were supplemented by review of the patient records and radiographs.
      Data collated included patient demographics, injury details, orthopaedic and
      plastic surgery operative details, and long-term outcomes. RESULTS: Between
      January 2013 and June 2016, 74 patients aged over 65 years were admitted with
      open lower limb fractures. 54 of these were open tibial fractures and these
      patients formed the study group. 19 patients required soft-tissue reconstruction
      for Gustilo and Anderson IIIB tibial fractures (age range, 67-95 years). In these
      patients, there were 7 midshaft (AO 42), 1 proximal (AO 41), and 11 distal (AO
      43) fractures. 13 patients were treated with internal fixation and 6 with
      circular frames. The median length of hospital stay was 27 days (range, 4-85). 14
      patients received loco-regional flaps and 5 underwent free tissue transfer with
      one requiring preoperative femoral angioplasty. There were no flap losses. Four
      patients had fasciocutaneous flaps, 3 tibialis anterior transposition, 2 an
      extensor digitorum brevis flap, 1 a hemisoleus flap, and 4 were skin grafted. All
      patients went on to unite and return to their premorbid weight-bearing status (4
      using walking frames, 3 using sticks, and 12 walking independently). CONCLUSION:
      Although the literature suggests a significantly higher complication rate in
      elderly patients with open fractures, we have demonstrated comparable rates of
      flap survival and bony union to those observed in younger patients. Challenges
      are presented in terms of patient physiology and these must be carefully managed
      pre- and postoperatively. These challenges are reflected in prolonged hospital
      stays.

PMID- 29588024
TI  - Effect of high frequency electromagnetic wave stimulation on muscle injury in a
      rat model.
AB  - INTRODUCTION: The aim of this study was to investigate biological changes in
      tissues with muscle contusion after the application of high frequency (HF)
      electromagnetic wave. METHODS: An acrylic pipe was placed on the right hind limb
      and a metallic ball was dropped inside the pipe, which resulted in a muscle
      contusion. After acquiring the optimal condition for muscle contusion, 20 Sprague
      Dawley rats were allocated to the HF treatment (N = 10) and sham groups (N = 10),
      which then underwent muscle contusion injury at their right thigh. The thickness
      and circumference of the right thigh and the left thigh (negative control groups)
      were measured (day 0). HF electromagnetic wave stimulation for three days was
      performed on the contusion area in the HF group after one day. Thickness was
      measured at the thickest area of both hind limbs and the circumference was
      measured every day for three days. The sham group received no treatment, and the
      circumference and thickness were measured using the same method. After three
      days, Hematoxylin and eosin and immunohistochemical (IHC) staining for IL-1beta
      were performed and TUNEL assay was conducted for apoptosis in the skin and muscle
      layers. RESULTS: The thigh muscle thickness at day 1 was significantly different
      between groups (P = 0.018) and this difference was observed between both sham and
      control groups (corrected P = 0.007), and between sham and HF groups (corrected P
      = 0.043). Thigh circumference was significantly different at day 3 (P = 0.047)
      and this difference was found between sham and control groups (corrected P =
      0.018), and between sham and HF groups (corrected P = 0.032). In the HF group,
      the inflammatory response was reduced to almost the same level as the control
      group. Evaluation of IL-1beta level, the inflammatory cytokine, through IHC
      showed marked localization of IL-1beta in muscle fibers of the sham group.
      However, significantly less IL-1beta was observed in the muscle of the HF
      treatment group. There was neither injury nor apoptosis after HF stimulation.
      CONCLUSIONS: Application of the HF showed therapeutic effect on muscle contusion
      by reducing muscle swelling. This effect might be caused by the anti-inflammatory
      action of the HF, which evoked energy into the injured muscle.

PMID- 29588025
TI  - General Genetic Strategies.
AB  - It is difficult to study the genetics and molecular mechanisms of anesthesia in
      humans. Fortunately, the genetic approaches in model organisms can, and have, led
      to profound insights as to the targets of anesthetics. In turn, the organization
      of these putative targets into meaningful pathways has begun to elucidate the
      mechanisms of action of these agents. However, it is important to first
      appreciate the strengths, and limitations, of genetic approaches to understand
      the anesthetic action. Here we compare the commonly used genetic model organisms,
      various anesthetic endpoints, and different modes of genetic screens. Coupled
      with the more specific data presented in subsequent chapters, this chapter places
      those results in a framework with which to analyze the discoveries across
      organisms and eventually extend the resulting models to humans.

PMID- 29588026
TI  - Approaches to Anesthetic Mechanisms: The C. elegans Model.
AB  - Understanding the mechanisms of volatile anesthetics has been a complex problem
      that has intrigued investigators for decades. Through the use of relatively
      simple model organisms-including the nematode Caenorhabditis elegans-progress has
      been made. Like any model system, C. elegans has both advantages and
      disadvantages, which are discussed in this chapter. Methods are provided for
      exposing worms to volatile anesthetics in airtight glass chambers, and for
      measuring the concentrations of anesthetic in the chambers by gas chromatography.
      In addition, various behavioral assays are described for characterizing the
      worms' responses to anesthetics. C. elegans identified proteins that play a role
      in anesthetic sensitivity that are highly conserved in other organisms, including
      humans. With precisely characterized neural development, C. elegans has also
      afforded an excellent opportunity to study anesthetic-induced neurotoxicity.
      Continued progress in understanding anesthetic action is anticipated from the
      ongoing study of C. elegans and other animal models.

PMID- 29588027
TI  - Using Drosophila to Understand General Anesthesia: From Synapses to Behavior.
AB  - Investigating mechanisms of general anesthesia requires access to multiple levels
      of neuronal function, from effects at individual synapses to responses in
      behaving animals. Drosophila melanogaster provides an excellent model to test
      different theories for general anesthesia because it offers robust methods for
      testing local as well as global target processes, in an animal that is similarly
      impacted by these diverse drugs as humans. Here, we outline methods to quantify
      two such endpoints, neurotransmission and behavioral responsiveness, focusing on
      the intravenous drug propofol.

PMID- 29588028
TI  - High-Throughput Screening to Identify Anesthetic Ligands Using Xenopus laevis
      Tadpoles.
AB  - General anesthetics are considered among the most significant advances in modern
      medicine; however, they are also some of the most dangerous commonly administered
      drugs. Despite this, the discovery of novel anesthetics has been slow, with few
      clinically used agents regardless of their nearly 200-year history. Xenopus
      laevis frogs have a long history as a model organism and provide a vital bridge
      between in vitro and preclinical mammalian assays. The provided protocols are
      efficient and cost-effective and therefore readily amendable for high-throughput
      evaluation of novel anesthetic ligands. By using the X. laevis bioassay, a
      researcher is capable of determining relative general anesthetic tolerance and/or
      cross-tolerance for candidate nonvolatile and/or volatile ligands.

PMID- 29588029
TI  - Zebrafish: A Pharmacogenetic Model for Anesthesia.
AB  - General anesthetics are small molecules that interact with and effect the
      function of many different proteins to promote loss of consciousness, amnesia,
      and sometimes, analgesia. Owing to the complexity of this state transition and
      the transient nature of these drug/protein interactions, anesthetics can be
      difficult to study. The zebrafish is an emerging model for the discovery of both
      new genes required for the response to and side effects of anesthesia. Here we
      discuss the tools available to manipulate the zebrafish genome, including both
      genetic screens and genome engineering approaches. Additionally, there are
      various robust behavior assays available to study anesthetic and other drug
      responses. These assays are available for single-gene study or high throughput
      for genetic or drug discovery. Finally, we present a case study of using propofol
      as an anesthetic in the zebrafish. These techniques and protocols make the
      zebrafish a powerful model to study anesthetic mechanisms and drug discovery.

PMID- 29588030
TI  - The Mouse as a Model Organism for Assessing Anesthetic Sensitivity.
AB  - The mouse has been used in many medical fields as a powerful model to reveal the
      genetic basis of human physiology and disease. The past two decades have
      witnessed an enormous wealth of genetic and informatic resources dedicated to
      this humble organism. With the ongoing revolution in mapping neural circuitry
      governing behavior, the mouse is an ideal model organism poised to unravel the
      mysteries of general anesthetic action. This chapter will describe and provide
      guidelines for anesthetic phenotyping in the mouse including both motor-dependent
      and motor-independent assessments.

PMID- 29588031
TI  - Identification of General Anesthetic Target Protein-Binding Sites by
      Photoaffinity Labeling and Mass Spectrometry.
AB  - General anesthetics are unique in that they represent a diverse range of chemical
      structures. Therefore, it is not surprising that the desired and undesired
      molecular targets, and binding sites therein, are as equally diverse and unique.
      Photoaffinity labeling has proven to be a valuable strategy for the
      identification of anesthetic molecular targets, as well as binding sites within
      those targets. In combination with the advances in mass spectrometry-based
      proteomics, along with the ability to comprehensively map posttranslational
      modifications, the method is likely to undergo continued improvement. Here, we
      provide the fundamentals for the design and development of an anesthetic
      photolabel. We also outline a protocol for the identification of photolabeled
      residues by mass spectrometry. The major steps include the photolabeling
      experiment, sample preparation, high-resolution mass spectrometry, and data
      analysis. The protocol can be used as a foundation for further optimization for
      the specific protein of interest and conditions of an experiment. The use of
      photoaffinity labeling adds an advantageous alternative and/or complementary
      approach to increase understanding of anesthetic molecular mechanisms.

PMID- 29588032
TI  - Xenon-Protein Interactions: Characterization by X-Ray Crystallography and Hyper
      CEST NMR.
AB  - The physiological activity of xenon has long been recognized, though the exact
      nature of its interactions with biomolecules remains poorly understood. Xe is an
      inert noble gas, but can act as a general anesthetic, most likely by binding
      internal hydrophobic cavities within proteins. Understanding Xe-protein
      interactions, therefore, can provide crucial insight regarding the mechanism of
      Xe anesthesia and potentially other general anesthetic agents. Historically, Xe
      protein interactions have been studied primarily through X-ray crystallography
      and nuclear magnetic resonance (NMR). In this chapter, we first describe our
      methods for preparing Xe derivatives of protein crystals and identifying Xe
      binding sites. Second, we detail our procedure for 129Xe hyper-CEST NMR
      spectroscopy, a versatile NMR technique well suited for characterizing the weak,
      transient nature of Xe-protein interactions.

PMID- 29588033
TI  - Computational Approaches to Studying Voltage-Gated Ion Channel Modulation by
      General Anesthetics.
AB  - Voltage-gated ion channels (VGICs) are responsible for the propagation of
      electrical signals in excitable cells. Small-molecule modulation of VGICs affects
      transmission of action potentials in neurons and thus can modulate the activity
      of the central nervous system. For this reason, VGICs are considered key players
      in the medically induced state of general anesthesia. Consistently, VGICs have
      been shown to respond to several general anesthetics. However, in spite of
      extensive electrophysiological characterizations, modulation of VGICs by
      anesthetics is still only partially understood. Among the challenging aspects are
      the presence of multiple binding sites and the observation of paradoxical
      effects, i.e., evidence, for the same channel, of inhibition and potentiation. In
      this context, molecular simulations emerged in the recent past as the tool of
      choice to complement electrophysiology studies with a microscopic picture of
      binding and allosteric regulation. In this chapter, we describe the most
      effective computational techniques to study VGIC modulation by general
      anesthetics. We start by reviewing the VGIC conduction cycle, the corresponding
      set of channel conformations, and the approaches used to model them. We then
      review the most successful strategies to identify binding sites and estimate
      binding affinities.

PMID- 29588034
TI  - Methods for Defining the Neuroprotective Properties of Xenon.
AB  - Xenon has features that make it an ideal general anesthetic agent; cost and
      scarcity mitigate xenon's widespread use in the operating room. Discovery of
      xenon's cytoprotective properties resulted in its application to thwart ongoing
      acute neurologic injury, an unmet clinical need. The discovery that xenon's
      neuroprotective effect interacts synergistically with targeted temperature
      management (TTM) led to its investigation in clinical settings, including in the
      management of the postcardiac arrest syndrome, in which TTM is indicated.
      Following successful demonstration of xenon's efficacy in combination with TTM in
      a preclinical model of porcine cardiac arrest, xenon plus TTM was shown to
      significantly decrease an imaging biomarker of brain injury for out of hospital
      cardiac arrest victims that had been successfully resuscitated. With the
      development of an efficient delivery system the stage is now set to investigate
      whether xenon improves survival, with good clinical outcome, for successfully
      resuscitated victims of a cardiac arrest.

PMID- 29588035
TI  - Xenon Anesthesia and CT: Noninvasive Measures of Brain Anesthetic Concentration.
AB  - The existence of a barrier between anesthetic behavioral state transitions has
      been observed across phyla, but demonstrating that such a barrier exists and is
      not a pharmacokinetic artifact has not yet been possible in humans. Such an
      investigation requires temporally precise information regarding the brain
      concentration of anesthetic in order to demonstrate the specific pharmacokinetic
      pharmacodynamic mismatch that is hysteresis. We propose a method to noninvasively
      determine brain tissue anesthetic concentration using computerized tomography and
      the radiopaque gaseous anesthetic xenon. Such a technique can be used to
      investigate pharmacokinetic-pharmacodynamic mismatches in humans.

PMID- 29588036
TI  - Physical Accuracy Leads to Biological Relevance: Best Practices For Simulating
      Ligand-Gated Ion Channels Interacting With General Anesthetics.
AB  - Efforts to detect binding modes of general anesthetics (GAs) for pentameric
      ligand-gated ion channels (pLGICs) are often complicated by a large number of
      indicated sites, as well as the challenges of ranking sites by affinity and
      determining which sites are occupied at clinical concentrations. Physics-based
      computational methods offer a powerful route for determining affinities of
      ligands to isolated binding sites, but preserving accuracy is essential. This
      chapter describes a step-by-step approach to multiple methods for identifying
      candidate sites and quantifying binding affinities and also discusses limitations
      and common pitfalls.

PMID- 29588037
TI  - Native System and Cultured Cell Electrophysiology for Investigating Anesthetic
      Mechanisms.
AB  - Anesthetic agents interact with a variety of ion channels and membrane-bound
      receptors, often at agent-specific binding sites of a single protein. These
      molecular-level interactions are ultimately responsible for producing the
      clinically anesthetized state. Between these two scales of effect, anesthetic
      agents can be studied in terms of how they impact the physiology of neuronal
      circuits, individual neurons, and cells expressing individual receptor types. The
      acutely dissected hippocampal slice is one of the most extensively studied and
      characterized preparations of intact neural tissue and serves as a highly useful
      experimental model system to test hypotheses of anesthetic mechanisms. Specific
      agent-receptor interactions and their effect on excitable membranes can further
      be defined with molecular precision in cell-based expression systems. We
      highlight several approaches in these respective systems that we have used and
      that also have been used by many investigators worldwide. We emphasize economy
      and quality control, to allow an experimenter to carry out these types of studies
      in a rigorous and efficient manner.

PMID- 29588038
TI  - Electrophysiological Analysis of Voltage-Gated Ion Channel Modulation by General
      Anesthetics.
AB  - Voltage-gated ion channels (VGICs) of excitable tissues are emerging as targets
      likely involved in both the therapeutic and toxic effects of inhaled and
      intravenous general anesthetics. Whereas sevoflurane and propofol inhibit voltage
      gated Na+ channels (Navs), sevoflurane potentiates certain voltage-gated K+
      channels (Kvs). The combination of these effects would dampen neural excitability
      and, therefore, might contribute to the clinical endpoints of general anesthesia.
      As the body of work regarding the interaction of general anesthetics with VGICs
      continues to grow, a multidisciplinary approach involving functional,
      biochemical, structural, and computational techniques, many of which are detailed
      in other chapters, has increasingly become necessary to solve the molecular
      mechanism of general anesthetic action on VGICs. Here, we focus on
      electrophysiological and modeling approaches and methodologies to describe how
      our work has elucidated the biophysical basis of the inhibition Navs by propofol
      and the potentiation of Kvs by sevoflurane.

PMID- 29588040
TI  - HCN and K2P Channels in Anesthetic Mechanisms Research.
AB  - The ability of a diverse group of agents to produce general anesthesia has long
      been an area of intense speculation and investigation. Over the past century, we
      have seen a paradigm shift from proposing that the anesthetized state arises from
      nonspecific interaction of anesthetics with the lipid membrane to the recognition
      that the function of distinct, and identifiable, membrane-embedded proteins is
      dramatically altered in the presence of intravenous and inhaled agents. Among
      proteinaceous targets, metabotropic and ionotropic receptors garnered much of the
      attention over the last 30 years, and it is only relatively recently that voltage
      gated ion channels have clearly and rigorously been shown to be important
      molecular targets. In this review, we will consider the experimental issues
      relevant to two important ion channel anesthetic targets, HCN and K2P.

PMID- 29588039
TI  - Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated
      Ion Channels.
AB  - General anesthetics are known to act in part by binding to and altering the
      function of pentameric ligand-gated ion channels such as nicotinic acetylcholine
      and gamma-aminobutyric acid type A receptors. Combining heterologous expression
      of the subunits that assemble to form these ion channels, mutagenesis techniques
      and voltage-clamp electrophysiology have enabled a variety of "structure
      function" approaches to questions of where anesthetic binds to these ion channels
      and how they enhance or inhibit channel function. Here, we review the evolution
      of concepts and experimental strategies during the last three decades, since
      molecular biological and electrophysiological tools became widely used. Topics
      covered include: (1) structural models as interpretive frameworks, (2) various
      electrophysiological approaches and their limitations, (3) Monod-Wyman-Changeux
      allosteric models as functional frameworks, (4) structural strategies including
      chimeras and point mutations, and (5) methods based on cysteine substitution and
      covalent modification. We discuss in particular depth the experimental design
      considerations for substituted cysteine modification-protection studies.

PMID- 29588041
TI  - Molecular Mechanics Parameterization of Anesthetic Molecules.
AB  - Anesthetic drug molecules are being increasingly studied through the use of
      computational methods such as molecular dynamics (MD). Molecular mechanics force
      fields require the investigator to supply parameters for the force field
      equation, which are not available for novel molecules. Careful selection of these
      parameters is critical for simulations to produce meaningful results. Therefore,
      this chapter presents a state-of-the-art method for determining these parameters
      by comparison to quantum mechanics calculations and experimental quantities.
      Ketamine is used as an example to demonstrate the process.

PMID- 29588042
TI  - Insights Into Receptor-Based Anesthetic Pharmacophores and Anesthetic-Protein
      Interactions.
AB  - General anesthetics are thought to allosterically bind and potentiate the
      inhibitory currents of the GABAA receptor through drug-specific binding sites.
      The physiologically relevant isoform of the GABAA receptor is a transmembrane
      ligand-gated ion channel consisting of five subunits (gamma-alpha-beta-alpha-beta
      linkage) symmetrically arranged around a central chloride-conducting pore.
      Although the exact molecular structure of this heteropentameric GABAA receptor
      remains unknown, molecular modeling has allowed significant advancements in
      understanding anesthetic binding and action. Using the open-channel conformations
      of the homologous glycine and glutamate-gated chloride receptors as templates, a
      homology model of the GABAA receptor was constructed using the Discovery Studio
      computational chemistry software suite. Consensus structural alignment of the
      homology templates allowed for the construction of a three-dimensional
      heteropentameric GABAA receptor model with (gamma2-beta3-alpha1-beta3-alpha1)
      subunit linkage. An anesthetic binding site was identified within the
      transmembrane alpha/beta intersubunit space by the convergence of three residues
      shown to be essential for anesthetic activity in previous studies with mutant
      mice (beta3-N265, beta3-M286, alpha1-L232). Propofol derivatives docked into this
      binding site showed log-linear correlation with experimentally derived GABAA
      receptor potentiation (EC50) values, suggesting this binding site may be
      important for receptor activation. The receptor-based pharmacophore was analyzed
      with surface maps displaying the predominant anesthetic-protein interactions,
      revealing an amphiphilic binding cavity incorporating the three residues involved
      in anesthetic modulation. Quantum mechanics calculations of the bonding patterns
      found in complementary high-resolution receptor systems further elucidated the
      complex nature of anesthetic-protein interactions.

PMID- 29588043
TI  - Understanding Anesthetic Mechanisms: Analysis of the Complex Kinetics of Ligand
      Gated Ion Channels.
AB  - Anesthetics modulate the response of ligand-gated ion channels to their
      neurotransmitter agonists, in a way that is consistent with clinical anesthesia:
      inhibition of synaptic transmission, by activation of inhibitory receptors and/or
      inhibition of excitatory receptors. Electrophysiological results for receptors
      such as GABAAR indicate that this modulation can be remarkably kinetically
      complex, characterized by concentration-dependent changes in the extent and
      (multiple) time scales of desensitization and deactivation. The full range of
      these features cannot be reproduced by a kinetic model in which anesthetic acts
      only by binding to putative protein sites, without having multiple sites with
      varying affinities, as well as many additional conformational states beyond the
      canonical set of three (resting, open, and desensitized). So, we discuss the
      implementation of a kinetic approach that incorporates only these three states,
      but accounts for effects of adsorption of anesthetic and agonist to the membrane
      in which the receptor is embedded, which modulates the conformational free energy
      landscape of the protein. As a result, the rate constants of conformational
      transitions become time dependent (non-Markovian), requiring nonstandard methods
      of kinetic analysis that can readily be implemented using available computational
      software.

PMID- 29588044
TI  - Preface.

PMID- 29588045
TI  - When Teachers Are Discovered to Have Sexually Abused Students: The Role of Child
      Psychiatric Consultation.
AB  - Tragically, investigations have shown many cases of teachers in private schools
      sexually abusing students.1 Most cases occurred from the 1960s through the 1990s
      and involved eccentric, creative, highly valued, and long-serving teachers. Some
      were indiscriminate predators who abused many children, others abused one or a
      few students, and some "groomed" students by developing a special emotional
      relationship during high school and then initiating a sexual relationship after
      graduation. Often, abusers and victims were vulnerable because of low self
      esteem, depression, divorce, or substance use. Most of the abuse concerned a male
      teacher and a female student, but some concerned same-sex teacher and student or
      a female teacher and a male student.

PMID- 29588046
TI  - Meta-Analyses in Child and Adolescent Psychiatry: Getting Closer to Clinical
      Practice.
AB  - Rigorously conducted meta-analyses provide evidence synthesis that has the
      potential to inform daily clinical decision making and development of clinical
      guidelines. In the past decade, there has been an increasing number of studies on
      pharmacologic and non-pharmacologic treatments for childhood and adolescent
      psychiatric disorders. Given this large body of research, busy clinicians might
      tend to rely on meta-analyses, rather than individual trials, to keep abreast of
      the evidence base supporting intervention strategies in child and adolescent
      psychiatry. Many meta-analyses focused on treatments for child and adolescent
      mental health problems have primarily addressed the question: Is treatment X more
      efficacious/effective (or safer) than the control condition? This is clearly an
      important starting point for clinicians when discussing with their patients and
      families the benefits and risks of treatment X, but clinicians need to know more.
      For instance, they might look for the evidence base to answer the following
      questions: Is treatment X the most efficacious and effective (or safest) option
      for my patient? When will treatment X likely start working? If the dose or
      intensity of the treatment does not seem to be effective, is it worthwhile to
      increase it? And if so, how?

PMID- 29588047
TI  - Promoting Success Across School Years for Children With Attention
      Deficit/Hyperactivity Disorder: Collaborative School-Home Intervention.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) typically
      experience significant difficulties in school, including academic
      underachievement and impairment in social relationships, such that they are at
      higher than average risk for special education placement, grade retention, school
      dropout, and lower lifetime educational attainment.1 The chronicity of ADHD
      symptoms and associated impairments requires proactive maintenance of treatment
      components across school years if amelioration of deleterious long-term outcomes
      is to be realized. Pfiffner et al.2 directly address the ongoing school
      impairments experienced by students with ADHD by following intensive intervention
      in 1 school year with booster treatment in a subsequent school year. The
      Collaborative Life Skills (CLS) program includes multiple components initially
      delivered over 10 to 12 weeks to train teachers in use of classroom
      accommodations and strategies (e.g., daily report card), parents in use of
      behavioral strategies at home and ways to collaborate with teachers, and children
      in social skills and independent task completion.

PMID- 29588048
TI  - "Communities" of Conditions: Novel Methods for Classifying Psychiatric Disorders.
AB  - In 1798, Philippe Pinel presented one of the first nosologies for psychiatric
      disorders, "Nosographie philosophique ou la methode de l'analyse appliquee a la
      medecine."1 His emphasis on psychological and physical conditions as the basis of
      mental illness provided a distinct departure from prior reliance on such
      etiologies such as demonic possession. Establishing classification schema was a
      much more profound innovation than a simple academic reordering of psychiatric
      phenomena-under Pinel's leadership at the famed Pitie-Salpetriere hospital, it
      also led to a radical reformation of clinical interventions, moving away from
      pseudoscientific practices toward psychologically based interventions. Much of
      this work influenced his successors in psychiatric taxonomy including Emil
      Kraeplin and others, ultimately forming the basis of the DSM.2 Although the DSM
      has been subsequently celebrated and maligned, it has been instrumental in both
      our conceptualization and treatment approach to psychiatric disorders. Indeed,
      there has been extensive effort to validate these conditions using factor
      analytic approaches to confirm that such conditions represent cohesive
      biologically based disorders, which has presented challenges.3.

PMID- 29588050
TI  - Sustained Effects of Collaborative School-Home Intervention for Attention
      Deficit/Hyperactivity Disorder Symptoms and Impairment.
AB  - OBJECTIVES: The Collaborative Life Skills (CLS) program is a school-home
      intervention for students with attention-deficit/hyperactivity disorder (ADHD)
      symptoms and impairment. CLS integrates school, parent, and student treatments
      followed by booster sessions during a maintenance period into the subsequent
      school year. The program is delivered by school-based mental health providers.
      Beneficial post-treatment effects have been documented. This study evaluated the
      effects of CLS after the maintenance period in the subsequent school year.
      METHOD: Using a cluster randomized design, schools within a large urban public
      school district were randomly assigned to CLS (12 schools) or usual services (11
      schools). Approximately 6 students participated at each school (N = 135, grade
      range = 2-5). Measures were completed at baseline, after treatment, and follow-up
      during the next school year. RESULTS: Students from schools assigned to CLS
      compared with those assigned to usual services showed significantly greater
      improvement at follow-up on parent, but not teacher, ratings of ADHD and
      oppositional defiant disorder symptom severity, organizational skills, and global
      impairment. Within-group analyses indicated that parent- and teacher-reported
      post-treatment gains for CLS in ADHD and oppositional defiant disorder symptoms,
      organizational skills, and academic competence were maintained into the next
      school year. CONCLUSIONS: These results extend support for CLS to the following
      school year by demonstrating sustained benefits on parent-reported ADHD and
      oppositional defiant disorder symptoms and functional impairment. The lack of
      significant teacher-reported differences between CLS and usual services
      highlights the need for further study of booster treatments for improving
      outcomes with new teachers across school years. CLINICAL TRIAL REGISTRATION
      INFORMATION: Study of the Collaborative Life Skills Program;
      http://clinicaltrials.gov; NCT01686724.

PMID- 29588049
TI  - The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric
      Anxiety Disorders: A Meta-Analysis.
AB  - OBJECTIVE: To determine the trajectory and magnitude of antidepressant response
      as well as the effect of antidepressant class and dose on symptomatic improvement
      in pediatric anxiety disorders. METHOD: Weekly symptom severity data were
      extracted from randomized, parallel group, placebo-controlled trials of selective
      serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine
      reuptake inhibitors (SNRIs) in pediatric anxiety disorders. Treatment response
      was modeled for the standardized change in continuous measures of anxiety using
      Bayesian updating. Posterior distributions for each study served as informative
      conjugate prior to distributions update subsequent study posteriors. Change in
      symptom severity was evaluated as a function of time, class and, for SSRIs,
      standardized dose. RESULTS: Data from 9 trials (SSRIs: n = 5; SNRIs, n = 4)
      evaluating 7 medications in 1,673 youth were included. In the logarithmic model
      of treatment response, statistically, but not clinically, significant treatment
      effects emerged within 2 weeks of beginning treatment (standardized medication
      placebo difference = -0.054, credible interval [CI] = -0.076 to -0.032, p = .005,
      approximate Cohen's d <= 0.2) and by week 6, clinically significant differences
      emerged (standardized medication-placebo difference = -0.120, CI = -0.142 to 
      0.097, p = .001, approximate Cohen's d = 0.44). Compared to SNRIs, SSRIs resulted
      in significantly greater improvement by the second week of treatment (p = .0268),
      and this advantage remained statistically significant through week 12 (all p
      values <.03). Improvement occurred earlier with high-dose SSRI treatment (week 2,
      p = .002) compared to low-dose treatment (week 10, p = .025), but SSRI dose did
      not have an impact on overall response trajectory (p > .18 for weeks 1-12).
      CONCLUSIONS: In pediatric patients with generalized, separation, and/or social
      anxiety disorders, antidepressant-related improvement occurred early in the
      course of treatment, and SSRIs were associated with more rapid and greater
      improvement compared to SNRIs.

PMID- 29588051
TI  - Data-Driven Subtyping of Executive Function-Related Behavioral Problems in
      Children.
AB  - OBJECTIVE: Executive functions (EF) are cognitive skills that are important for
      regulating behavior and for achieving goals. Executive function deficits are
      common in children who struggle in school and are associated with multiple
      neurodevelopmental disorders. However, there is also considerable heterogeneity
      across children, even within diagnostic categories. This study took a data-driven
      approach to identify distinct clusters of children with common profiles of EF
      related difficulties, and then identified patterns of brain organization that
      distinguish these data-driven groups. METHOD: The sample consisted of 442
      children identified by health and educational professionals as having
      difficulties in attention, learning, and/or memory. We applied community
      clustering, a data-driven clustering algorithm, to group children by similarities
      on a commonly used rating scale of EF-associated behavioral difficulties, the
      Conners 3 questionnaire. We then investigated whether the groups identified by
      the algorithm could be distinguished on white matter connectivity using a
      structural connectomics approach combined with partial least squares analysis.
      RESULTS: The data-driven clustering yielded 3 distinct groups of children with
      symptoms of one of the following: (1) elevated inattention and
      hyperactivity/impulsivity, and poor EF; (2) learning problems; or (3) aggressive
      behavior and problems with peer relationships. These groups were associated with
      significant interindividual variation in white matter connectivity of the
      prefrontal and anterior cingulate cortices. CONCLUSION: In sum, data-driven
      classification of EF-related behavioral difficulties identified stable groups of
      children, provided a good account of interindividual differences, and aligned
      closely with underlying neurobiological substrates.

PMID- 29588053
TI  - Gun- and Non-Gun-Related Violence Exposure and Risk for Subsequent Gun Carrying
      Among Male Juvenile Offenders.
AB  - OBJECTIVE: Although studies have found that youth exposed to violence are more
      likely to carry guns than non-exposed youth, this association could be due to
      common causal factors or other pre-existing differences between individuals. In
      this study, within-individual change models were used to determine whether
      juvenile offenders exhibit an increased propensity to carry a firearm after being
      exposed to gun violence and/or non-gun violence. The advantage of this approach
      is all time-invariant factors are eliminated as potential confounders. METHOD: A
      sample of 1,170 racially/ethnically diverse male juvenile offenders was recruited
      in Arizona and Pennsylvania (14-19 years old at recruitment). Participants were
      interviewed every 6 months for 3 years followed by 4 annual assessments. The
      outcome was gun carrying and the primary predictors were exposure to gun violence
      and non-gun violence. Time-varying covariates included exposure to peers who
      carried guns, exposure to peers who engaged in other (non-gun) criminal acts,
      developmental changes in gun carrying, and changes in gun carrying from
      incarceration or institutionalization. RESULTS: Adolescent offenders were
      significantly more likely to carry a gun in recall periods after exposure to gun
      violence, but not after exposure to non-gun violence. Effect of gun violence on
      carrying was significant throughout adolescence and young adulthood and could not
      be accounted for by time-varying and time-invariant confounders. CONCLUSIONS:
      Interventions to decrease illegal gun carrying should target young men in medical
      and mental health settings who experience or witness gun violence and those
      living in communities with high rates of gun violence.

PMID- 29588052
TI  - Suicidal Thoughts and Behaviors Among First-Year College Students: Results From
      the WMH-ICS Project.
AB  - OBJECTIVE: College entrance may be a strategically well-placed "point of capture"
      for detecting late adolescents with suicidal thoughts and behaviors (STB).
      However, a clear epidemiological picture of STB among incoming college students
      is lacking. We present the first cross-national data on prevalence as well as
      socio-demographic and college-related correlates for STB among first-year college
      students. METHOD: Web-based self-report surveys were obtained from 13,984 first
      year students (response rate 45.5%) across 19 colleges in 8 countries (Australia,
      Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain, and the United
      States). RESULTS: Lifetime prevalence of suicidal ideation, plans, and attempts
      was 32.7%, 17.5%, and 4.3%, respectively. The 12-month prevalence was 17.2%,
      8.8%, and 1.0%, respectively. About three-fourths of STB cases had onset before
      the age of 16 years (Q3 = 15.8), with persistence figures in the range of 41% to
      53%. About one-half (53.4%) of lifetime ideators transitioned to a suicide plan;
      22.1% of lifetime planners transitioned to an attempt. Attempts among lifetime
      ideators without plan were less frequent (3.1%). Significant correlates of
      lifetime STB were cross-nationally consistent and generally modest in effect size
      (median adjusted odds ratio [aOR] = 1.7). Nonheterosexual orientation (aOR range
      3.3-7.9) and heterosexual orientation with some same-sex attraction (aOR range
      1.9-2.3) were the strongest correlates of STB, and of transitioning from ideation
      to plans and/or attempts (aOR range 1.6-6.1). CONCLUSION: The distribution of STB
      in first-year students is widespread, and relatively independent of socio
      demographic risk profile. Multivariate risk algorithms based on a high number of
      risk factors are indicated to efficiently link high-risk status with effective
      preventive interventions.

PMID- 29588054
TI  - Prevalence of Mental Disorder and Service Use by Immigrant Generation and
      Race/Ethnicity Among U.S. Adolescents.
AB  - OBJECTIVE: To examine differences in lifetime prevalence of mental disorder and
      service use among U.S. adolescents by both immigrant generation and
      race/ethnicity. METHOD: A total of 6,250 adolescents aged 13 to 18 years in the
      National Comorbidity Survey Replication Adolescent Supplement were assessed for
      lifetime prevalence of mood and/or anxiety disorders, behavior disorders, and
      mental health service use. Twelve groups defined by self-identified
      race/ethnicity (non-Hispanic white, Hispanic, non-Hispanic black, Asian) and
      immigrant generation (first, second, third, or more) were compared. RESULTS:
      Differences in prevalence of lifetime mental disorder were most apparent when
      immigrant generation and race/ethnicity were considered jointly. Compared to
      third+generation non-Hispanic white adolescents, the odds of mood/anxiety
      disorder were increased among second-generation Asian (adjusted odds ratio [AOR]
      = 2.51; 95% CI = 1.22-5.17) and third+generation Hispanic (AOR = 1.28; 95% CI =
      1.00-1.63) but reduced among first-generation Asian (AOR = 0.27; 95% CI = 0.10
      0.71) and second-generation non-Hispanic white adolescents (AOR = 0.50; 95% CI =
      0.30-0.81). The odds of behavior disorder were lower among first-generation Asian
      (AOR = 0.26; 95% CI = 0.09-0.71) and all generations of non-Hispanic black
      adolescents (AOR range 0.43-0.55). Adjusting for lifetime disorder, first
      generation Hispanic and non-Hispanic white adolescents and all generations of non
      Hispanic black adolescents were less likely to receive mental health services
      (AOR range 0.24-0.55). CONCLUSIONS: Variation in risk of disorder by immigrant
      generation and race/ethnicity underscores the importance of considering social,
      economic, and cultural influences in etiologic and treatment studies of
      adolescent psychopathology. Lower rates of service use, particularly among first
      generation immigrant adolescents, highlight the need to identify and address
      barriers to recognition and treatment of mental disorders among adolescents from
      immigrant and racial/ethnic minority backgrounds.

PMID- 29588055
TI  - Mirtazapine and Weight Gain in Avoidant and Restrictive Food Intake Disorder.
AB  - Avoidant and restrictive food intake disorder (ARFID) is a newly classified
      disorder in the DSM-5 that describes a pattern of restrictive eating across the
      lifespan that results in significant weight loss, nutritional deficiency,
      dependence on enteral feeding or nutritional supplements, or marked interference
      in psychosocial functioning.1 Currently, there are no evidence-based treatment
      approaches or medications for this disorder.2 We have administered a range of
      psychoactive medications to those with ARFID in our treatment program in an
      attempt to find an effective medication. One medication of interest has been
      mirtazapine because it promotes appetite and weight gain, decreases nausea and
      vomiting, and improves gastric emptying. Although mirtazapine is an off-label
      approach in a pediatric population and carries a black box warning for an
      increased risk of suicide, it is an effective treatment for depression and
      anxiety symptoms in adults and is generally well tolerated.3,4 There are no
      studies to date reporting on the use of mirtazapine in patients with ARFID.

PMID- 29588056
TI  - MBT From A to Z.

PMID- 29588057
TI  - [Association of macular coloboma and Pierre Robin sequence; could it be Stickler
      syndrome?]

PMID- 29588058
TI  - [Manual small incision cataract surgery: Experience of a regional eye care
      service in Togo].
AB  - In order to fight against blindness in the central region of Togo, a project was
      implemented in a partnership between the Ministry of Health and an international
      Non-Governmental Organization: the Swiss Red Cross. Cataract surgery underwent an
      annual audit of the research-action type, in order to improve the functional
      results of patients. One of the recommendations of these audits was the
      introduction of manual small incision surgery in place of the classic
      extracapsular technique. This study had for its objective to evaluate the
      functional results and follow-up of patients undergoing the new technique
      compared with quality standards of cataract surgery according to the World Health
      Organization. This study was carried out by retrospective analysis of records and
      operative reports of patients over twenty years of age undergoing manual small
      incision cataract surgery from June 2012 to June 2015. Out of a total of 1292
      patients undergoing cataract surgery in the five districts covered by the project
      during the same period, 1003 patients met the inclusion criteria (77.63 %). Among
      the 1003 cases, 504 (50.25 %) were male, while 499 (49.75 %) were female. The
      overall mean age was 62 years. The cataract was total in 84.65 % of cases and
      partial in 15.35 % of cases where visual acuities were quantifiable.
      Postoperative complications were dominated by corneal edema (22 %). On the first
      postoperative day, the good results (visual acuity>=3/10), the average results
      (visual acuity between 3/10 and 1/10) and the poor results (visual acuity<1/10)
      were respectively 41.2 %, 50.60 % and 8.2 % without optical correction, changing
      to 64.40 %, 28.90 % and 6.70 % after optical correction. Between the first and
      third week, 855 patients (85 %) were seen again. The good, average and poor
      results were respectively 61.90 %, 35.70 % and 2.40 % without correction, going
      to 85.30 %, 12.70 % and 2 % after optical correction. Among the 85.30 % good
      results, 53 % had a visual acuity>=5/10. Residual ametropias are the main cause
      of poor functional results and the introduction of biometry can contribute to
      their improvement. Cataract surgery through a well-controlled manual small
      incision is a promising alternative to the technique of choice,
      phacoemulsification, which is not yet widely accessible in our low-income
      countries.

PMID- 29588059
TI  - Lysophosphatidylinositols, from Cell Membrane Constituents to GPR55 Ligands.
AB  - Lysophosphatidylinositols (LPIs) are membrane constituents that alter the
      properties of said membranes. However, recent data showing that the once orphan
      receptor, GPR55, can act as a receptor for LPIs has sparked a renewed interest in
      LPIs as bioactive lipids. As evidence supporting the importance of LPIs and/or
      GPR55 is continuously accumulating and because LPI levels are altered in a number
      of pathologies such as obesity and cancer, the coming years should bring new,
      exciting discoveries to this field. In this review, we discuss the recent work on
      LPIs and on their molecular target, the GPR55 receptor. First, we summarize the
      metabolism of LPIs before outlining the cellular pathways activated by GPR55.
      Then, we review the actions of LPIs and GPR55 that could have potential
      pharmacological or therapeutic applications in several pathophysiological
      settings, such as cancer, obesity, pain, and inflammation.

PMID- 29588060
TI  - Light Therapy in Parkinson's Disease: Towards Mechanism-Based Protocols.
AB  - A growing body of work is investigating the safety and efficacy of light in
      Parkinson's disease (PD). Here we discuss the potential of this emerging therapy
      to improve both motor and non-motor symptoms of PD. We also highlight directions
      for future basic, translational, and clinical research that are critical for the
      development of mechanism-based protocols of light therapy in PD.

PMID- 29588061
TI  - Pre-surgical register of tobacco consumption.
AB  - INTRODUCTION AND OBJECTIVE: Smoking cessation before surgery decreases the risk
      of complications. The aim of this study was to analyse the smoking register,
      associated variables and a short talk given to smokers in pre-surgical visits.
      MATERIAL AND METHOD: Cross-sectional study. The pre-surgical records of 680
      patients were assessed. We selected patient sociodemographic variables, surgical
      intervention characteristics, smoking status and consumption pattern. Logistic
      regression was used to study the variables association with smoking. RESULTS: A
      percentage of 97.2 of the pre-surgical records include information on tobacco
      consumption. Overall 20% of surgical patients are smokers. The probability of
      smoking is higher among men (adjusted odds ratio [aOR] 2.6, 95% confidence
      interval [CI] 1.7-4.0) and<=60 years (aOR 5.4, 95% CI 3.2-9.1). None of the
      records had information regarding a short talk given to patients to give up
      smoking. CONCLUSION: Smoking consumption was prevalent, but the characterisation
      of a smoker's profile and short talk given to patient before surgery was
      practically nonexistent. Ensuring that patients who smokes receives a short talk
      to give up smoking before surgery is necessary.

PMID- 29588062
TI  - Impact of aerobic exercise on cognitive impairment and oxidative stress markers
      in methamphetamine-dependent patients.
AB  - This study aimed to investigate whether 12-week moderate-intensity aerobic
      exercise has beneficial effects on oxidative stress markers in blood and on
      cognitive functions in patients who have methamphetamine dependence. Serum levels
      of oxidative stress markers, including total anti-oxidation capability, super
      oxide dismutase (SOD), catalase (CAT), and methane dicarboxylic aldehyde (MDA),
      were measured at baseline (all participants) and the 12-week follow-up
      (methamphetamine-dependent patients). Serum levels of CAT and MDA in
      methamphetamine-dependent patients (n = 68) were higher than those in healthy
      controls (n = 35) at baseline. Furthermore, the international shopping list (ISL)
      task scores of methamphetamine-dependent patients were significantly lower than
      those of the controls, indicating verbal memory deficits in methamphetamine
      dependent patients. Although there were no significant interactions for all
      cognitive function scores, aerobic exercise improved the processing speed in
      methamphetamine-dependent patients. Of interest, aerobic exercise significantly
      attenuated a spontaneous increase in serum MDA levels in methamphetamine
      dependent patients after 12-weeks of abstinence. In conclusion, this study showed
      that methamphetamine-dependent patients with verbal learning and memory deficits
      have higher serum levels of MDA, and that a 12-week aerobic exercise program may
      have beneficial effects on the processing speed as well as blood lipid
      peroxidation in methamphetamine-dependent patients.

PMID- 29588063
TI  - Evidence for a relatively high proportion of DM2 mutations in a large group of
      Polish patients.
AB  - INTRODUCTION: Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are
      autosomal dominant, multisystem disorders, considered the most common dystrophies
      in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP
      genes, respectively. METHODS: Molecular analyses were performed by PCR and the
      modified RP-PCR in patients, in their at-risk relatives and prenatal cases.
      RESULTS: The analysis of Polish controls revealed the range of 5-31 CTG repeats
      for DM1 and 110-228 bp alleles for DM2. Among 318 confirmed probands - 196 (62%)
      were DM1 and 122 (38%) - DM2. Within DM1families, 10 subjects carried a low
      expanded CTG tract (< 100 repeats), which resulted in a full mutation in
      subsequent generations. Two related individuals had unstable alleles-188 bp and
      196 bp without common interruptions. CONCLUSION: The relative frequencies of
      DM1/DM2 among Polish patients were 68% and 32%, respectively, with a relatively
      high proportion of DM2 mutations (1.6:1).

PMID- 29588064
TI  - The evaluation of the effects of steroid treatment on the tumor and peritumoral
      edema by DWI and MR spectroscopy in brain tumors.
AB  - OBJECTIVE: To investigate the effects of dexamethasone on brain tumor and
      peritumoral edema by different sequences of magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: MRI was performed in 28 patients with brain tumor.
      Patients were divided into the 3 groups based on the histological diagnosis;
      Group I: high-grade glial tumor, Group II: low-grade glial tumor, and Group III:
      brain metastasis. The measurements of peritumoral edema volume and apparent
      diffusion coefficient (ADC) values were performed while the peak areas of
      cerebral metabolites were measured by spectroscopy in groups I and II. The
      changes in edema volumes, ADC values and cholin/creatine peak areas were
      compared. RESULTS: The volume of peritumoral edema was decreased in groups I and
      II, but increased in group III after dexamethasone treatment. These changes were
      not statistically significant for 3 groups. ADC value was decreased in group I
      and increased in groups II and III. Changes in ADC values were statistically
      significant. Cholin/creatine peak areas were decreased after dexamethasone in
      groups I and II, but these changes were also not significant. CONCLUSION:
      Dexamethasone has no significant effect on the volume of peritumoral edema in
      glial tumor and metastasis. Moreover, dexamethasone increases the fluid movements
      in low grade gliomas and metastases, decreases in high grade gliomas. However,
      more comprehensive clinical studies are needed to show the effects of
      dexamethasone on brain tumors and peritumoral edema.

PMID- 29588065
TI  - Atypical Presentation of Escherichia coli Monomicrobial Necrotizing Fasciitis in
      a Renal Transplant Patient: A Case Report.
AB  - Skin and soft tissue infections (SSTIs) are one of most frequent infectious
      causes for referral to the emergency department and one of the most frequent
      infectious causes of hospital admissions. Escherichia coli, the most commonly
      occurring gram-negative pathogen involved in these infections, contributes to
      about 7% of all SSTIs cases where gram-positive organisms reign dominant.
      Patients are more susceptible to these gram-negative SSTIs if they are
      neutropenic, have hematologic malignancies, have undergone solid organ or
      hematopoietic transplantation, or have cirrhotic liver disease. Due to their
      immunocompromised state, the prognosis is very poor and not well understood. We
      report a case of an atypical presentation of an E coli monomicrobial necrotizing
      fasciitis in a renal transplant patient. Our findings support improved mortality
      with rapid aggressive interventions, such as amputation, in immunocompromised
      patients.

PMID- 29588066
TI  - Life-Threatening Everolimus-Associated Pneumonitis: A Case Report and a Review of
      the Literature.
AB  - INTRODUCTION: Noninfective pneumonitis is a class-related effect within mammalian
      target of rapamycin (mTOR) inhibitors, including everolimus, and can occasionally
      be severe. CASE REPORT: A 62-year-old man, medicated with everolimus due to a
      heart transplantation 17 years previously and with chronic kidney disease, was
      admitted to the intensive care unit (ICU) with acute respiratory failure,
      cardiovascular shock, and impaired renal function requiring dialysis. Computed
      tomography (CT) scan revealed right upper lobe consolidation. Extensive
      microbiological workup, autoimmune testing, and cytology were negative and
      echocardiography showed preserved heart function. Everolimus levels were normal
      (5.7-6.1 ng/mL) and the drug was suspended at day 9. The patient was difficult to
      ventilate and responded poorly to broad-spectrum antibiotic and antifungal
      therapy. On day 25, CT scan and bronchoscopy revealed left-sided alveolar
      hemorrhage, and corticosteroid pulses were performed. The patient gradually
      improved. After discharge and 6 months of follow-up, clinical recovery was
      complete and chest imaging substantially improved. DISCUSSION: Pneumonitis occurs
      in up to 4.3% of transplant recipients using everolimus for immunosuppression.
      Despite usually presenting as a mild and self-limited disease, severe cases have
      been described. Alveolar hemorrhage can occur and is associated with poor
      outcome. Everolimus levels do not seem to accurately predict toxicity.
      Corticosteroid therapy has been used with success in severe disease. We review
      the pathophysiological, clinical, and management-related aspects of this entity
      with emphasis on its potential severity. CONCLUSION: Our case was a rare
      occurrence of severe life-threatening pulmonary disease related to everolimus.
      Awareness of the potential severity of this entity is important for the
      management of patients using mTOR inhibitors.

PMID- 29588067
TI  - Particularized trust, generalized trust, and immigrant self-rated health: cross
      national analysis of World Values Survey.
AB  - OBJECTIVES: This research examined the associations between two types of trust,
      generalized and particularized, and self-rated health among immigrants. STUDY
      DESIGN: Data were drawn from the World Values Survey (WVS6), the latest wave of
      cross-sectional surveys based on face-to-face interviews. METHODS: The immigrant
      subsample analyzed herein contains 3108 foreign-born individuals clustered from
      51 countries. Given the hierarchically nested data, two-level logistic
      regressions models were estimated using HLM (Hierarchical Linear Modeling) 7.1.
      RESULTS: At the individual level, net of socio-economic and demographic factors
      (age, gender, marital status, education, income, neighborhood security, and
      subjective well-being), particularized trust was positively related to physical
      health (odds ratio [OR] = 1.11, P < .001). Generalized trust, however, was not a
      significant predictor. At the country level, based on alternative models, the
      aggregate measure of particularized trust was negatively associated with
      subjective health. The odds of being healthy were on average about 30% lower.
      CONCLUSION: The interdisciplinary literature on social determinants of health has
      largely focused on the salubrious impact of trust and other forms of social
      capital on physical well-being. Many previous studies based on general, not
      immigrant, populations also did not differentiate between generalized and
      particularized types of trust. Results from this study suggest that this
      conceptual distinction is critical in understanding how and to what extent the
      two are differentially related to immigrant well-being across multiple levels of
      analysis.

PMID- 29588068
TI  - Evolving parent-adult child relations: location of multiple children and
      psychological well-being of older adults in China.
AB  - OBJECTIVE: This study examines the interplay among intergenerational emotional
      closeness, location of multiple children, and parental depressive symptoms in the
      context of massive migration in rural China. STUDY DESIGN: This study is based on
      a longitudinal survey. METHODS: Longitudinal data were collected from a
      stratified random sample of age 60 years and older living in rural townships
      within Chaohu, a primarily agricultural municipal district with massive out
      migration in China. In 2009, 1224 individuals completed the survey, and 977
      (79.8% of the original participants) were followed up in 2012. We estimate fixed
      effects models to examine how changing collective emotional cohesion and the
      total composition of children's location affect parents' depressive symptoms.
      RESULTS: Descriptive analyses show that both the composition of children's
      location and intergenerational emotional closeness are subject to changes during
      a 3-year survey interval. Results from fixed-effect models further demonstrate
      that collective emotional closeness and psychological well-being are positively
      associated with each other. This association is the strongest when all children
      are local, but it becomes less prominent when there are more migrant than local
      children. CONCLUSIONS: This study has provided important evidence that both
      intergenerational cohesion and location of multiple children evolve over time and
      jointly influence parents' psychological well-being in later life. The left
      behind older adults are not necessarily the most vulnerable group in rural China.
      Those with most adult children living close by could also suffer from a deficit
      in psychological well-being if the emotional bond between them is weak.

PMID- 29588069
TI  - Antigen-Specific Tolerization and Targeted Delivery as Therapeutic Strategies for
      Autoimmune Diseases.
AB  - The prevalence of autoimmune disorders is increasing steadily and there is no
      permanent cure available. Immunomodulation through repeated exposure of antigens,
      known as antigen-specific immune tolerance or antigen-specific immunotherapy
      (ASI), is a promising approach to treat or prevent autoimmune disorders.
      Different optimization protocols (immunization routes, delivery systems, and
      approaches) are being developed to implement ASI against self-proteins. Including
      appropriate adjuvants, altered peptide ligand, and using multipeptides are
      approaches that can be used to specifically target autoimmunity. This review
      explores various ASI application methods, including different routes of antigen
      specific sensitization, delivery systems, immunomodulators containing specific
      antigens, and other targeted approaches that have been successfully demonstrated
      to have therapeutic effects on autoimmune diseases.

PMID- 29588070
TI  - Parasite allergens.
AB  - Human IgE against helminths is a normal component of the whole protective
      response elicitesd during infection, when specific IgE to a great number of
      antigens is produced; however, few of those IgE binding components are actually
      allergens. In general, considering the strong Th2/IgE responses during helminth
      infections is intriguing that they are not usually associated with allergic
      symptoms, which probably (but not exclusively) depends on parasite-induced
      immunomodulation. However, allergic manifestations have been described during
      some helminth infections such as ascariasis, strongyloidiasis, anisakiasis and
      hydatidosis. In addition, there is evidence that helminthiases (e.g. ascariasis)
      can increase symptoms in allergic patients. Furthermore, allergic reactions
      during anti-helminth vaccination have been observed, a problem that also could be
      associated to the future use of parasite derived immunomodulators. Therefore,
      identification and characterization of helminth allergens is a matter of
      increasing research and a great number of IgE binding antigens have been found
      (www.allergen.org and www.allergome.org). Here we describe only a small group of
      them, for which allergenic activity (the ability to induce IgE mediated
      inflammation) have been clinical or experimentally demonstrated. Ascaris
      lumbricoides tropomyosin (Asc l 3) has strong allergenic activity; in the Tropics
      it has been associated with asthma and asthma severity, suggesting clinical
      relevance. In addition, due to its cross reactivity with mite tropomyosins this
      allergen could influence house dust mite (HDM) allergy diagnosis. Characterized
      Ascaris allergens also include the polyprotein As s 1 (ABA-1) and the Glutathione
      transferase As l 13. Other helminth allergens include Anisakis simplex Ani s 1,
      Ani s 4, Ani s 7 and Ani s 9; Necator americanus NaASP2q and Nacal1 and
      Schistosoma mansoni SmVAL4 and Sm22.6. Future work on helminth IgE binding
      antigens will help to understand several aspects of allergenicity and allergenic
      activity, among them the increasing finding of IgE binding molecules that not
      induce allergic symptoms.

PMID- 29588071
TI  - Cryptic Species - More Than Terminological Chaos: A Reply to Heethoff.

PMID- 29588072
TI  - Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late
      outcomes from two prospective clinical trials.
AB  - PURPOSE: Optimal prostate SABR dose-fractionation is unknown. This study compares
      long-term outcomes from two prospective trials. METHODS: Study1 patients had low
      risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and
      received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2. RESULTS: 114
      patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6
      years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8
      in study1, 1 in study2); two were managed with ADT and four had local salvage.
      The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years
      for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years
      if PSA >=0.4 (p = 0.02). Nine patients died, none of PCa. No patient has
      metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25)
      and 100%. CONCLUSIONS: Dose-escalated prostate SABR was associated with lower
      nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a
      predictor of biochemical control. Half of patients with BF were successfully
      salvaged. Given that this is a favorable-risk cohort, longer follow-up will be
      needed to see if the lower nPSA translates into lower BF rates.

PMID- 29588073
TI  - miR-22 regulates C2C12 myoblast proliferation and differentiation by targeting
      TGFBR1.
AB  - Recently, miR-22 was found to be differentially expressed in different skeletal
      muscle growth period, indicated that it might have function in skeletal muscle
      myogenesis. In this study, we found that the expression of miR-22 was the most in
      skeletal muscle and was gradually up-regulated during mouse myoblast cell (C2C12
      myoblast cell line) differentiation. Overexpression of miR-22 repressed C2C12
      myoblast proliferation and promoted myoblast differentiation into myotubes,
      whereas inhibition of miR-22 showed the opposite results. During myogenesis, we
      predicted and verified transforming growth factor beta receptor 1 (TGFBR1), a key
      receptor of the TGF-beta/Smad signaling pathway, was a target gene of miR-22.
      Then, we found miR-22 could regulate the expression of TGFBR1 and down-regulate
      the Smad3 signaling pathway. Knockdown of TGFBR1 by siRNA suppressed the
      proliferation of C2C12 cells but induced its differentiation. Conversely,
      overexpression of TGFBR1 significantly promoted proliferation but inhibited
      differentiation of the myoblast. Additionally, when C2C12 cells were treated with
      different concentrations of transforming growth factor beta 1 (TGF-beta1), the
      level of miR-22 in C2C12 cells was reduced. The TGFBR1 protein level was
      significantly elevated in C2C12 cells treated with TGF-beta1. Moreover, miR-22
      was able to inhibit TGF-beta1-induced TGFBR1 expression in C2C12 cells.
      Altogether, we demonstrated that TGF-beta1 inhibited miR-22 expression in C2C12
      cells and miR-22 regulated C2C12 cell myogenesis by targeting TGFBR1.

PMID- 29588074
TI  - Use of French healthcare insurance databases in pediatric pharmacoepidemiology.
AB  - The French healthcare insurance databases have proven to be valuable tools for
      the conduct of pharmaco-epidemiological studies with regards to the size of the
      population covered and that of the available information. Their wider use in the
      field of pediatric pharmacoepidemiology is of paramount importance given the
      existing gap of knowledge in the use and effects of many drugs in children and
      adolescents as well as the difficulties to conduct clinical research studies in
      this age population. However, because of the architectural complexity of these
      databases and their specificities, specific expertise should be developed in
      order to ensure the reliability of studies based on these data. To this purpose,
      it is important to facilitate knowledge sharing through national collaborative
      projects.

PMID- 29588075
TI  - Surgical management of functional constipation: An intermediate report of a new
      approach using a laparoscopic sigmoid resection combined with malone
      appendicostomy.
AB  - INTRODUCTION: We previously reported our surgical technique for functional
      constipation for patients who have failed medical management using a novel
      collaborative approach with gastroenterology input, pre-operative contrast enema,
      colonic manometry, and laxative protocol combined with a laparoscopic colonic
      resection with Malone appendicostomy. Now we report our intermediate outcomes.
      METHODS: Patients who failed bowel management program for functional constipation
      were reviewed from 3/2014-2/2017. Patients with Hirschsprung disease, anorectal
      malformation, tethered cord, spina bifida, Trisomy 21, cerebral palsy,
      mitochondrial disease, or prior colon resection were excluded. RESULTS: Of 31
      patients (14 females; median age 12years, follow-up 10.3months) with functional
      constipation and failed medical management, 26 (84%) had preoperative colonic
      manometry which, in addition to the contrast enema, guided laparoscopic colon
      resection. Ten patients (32.3%) are clean with no flushes (1 takes no laxatives,
      8 are on low dose laxatives only, and 1 patient was clean on laxatives but chose
      to switch back to flushes). Of the 21 patients that remain on antegrade flushes,
      20 (95.2%) are clean, and one patient (4.8%) continues to soil. We define clean
      as no soiling and no abnormal stool burden on x-ray. Laxative trials are planned
      for all patients on an antegrade flush regimen. CONCLUSION: Our intermediate
      results show that laparoscopic colon resection with Malone appendicostomy allows
      the majority of patients to be clean on antegrade flushes, and some to be on no
      or minimal laxatives. TYPE OF STUDY: Retrospective review. LEVEL OF EVIDENCE: 3.

PMID- 29588076
TI  - Intestinal resection-associated metabolic syndrome.
AB  - BACKGROUND: Short bowel syndrome occurs following massive small bowel resection
      (SBR) and is one of the most lethal diseases of childhood. We have previously
      demonstrated hepatic steatosis, altered gut microbiome, and increased fat
      deposition in our murine model of SBR. These novel findings prompted us to
      investigate potential alterations in glucose metabolism and systemic inflammation
      following intestinal resection. METHODS: Male C57BL6 mice underwent 50% proximal
      SBR or sham operation. Body weight and composition were measured. Fasting blood
      glucose (FBG), glucose, and insulin tolerance testing were performed. Small
      bowel, pancreas, and serum were collected at sacrifice and analyzed. RESULTS: SBR
      mice gained less weight than shams after 10weeks. Despite this, FBG in resected
      mice was significantly higher than sham animals. After SBR, mice demonstrated
      perturbed body composition, higher blood glucose, increased pancreatic islet
      area, and increased systemic inflammation compared with sham mice. Despite these
      changes, we found no alteration in insulin tolerance after resection.
      CONCLUSIONS: After massive SBR, we present evidence for abnormal body
      composition, glucose metabolism, and systemic inflammation. These findings,
      coupled with resection-associated hepatic steatosis, suggest that massive SBR
      (independent of parenteral nutrition) results in metabolic consequences not
      previously described and provides further evidence to support the presence of a
      novel resection-associated metabolic syndrome.

PMID- 29588077
TI  - Fatigue failure load of two resin-bonded zirconia-reinforced lithium silicate
      glass-ceramics: Effect of ceramic thickness.
AB  - OBJECTIVES: To evaluate the effect of ceramic thickness on the fatigue failure
      load of two zirconia-reinforced lithium silicate (ZLS) glass-ceramics, adhesively
      cemented to a dentin analogue material. METHODS: Disc-shaped specimens were
      allocated into 8 groups (n=25) considering two study factors: ZLS ceramic type
      (Vita Suprinity - VS; and Celtra Duo - CD), and ceramic thickness (1.0; 1.5; 2.0;
      and 2.5mm). A trilayer assembly (phi=10mm; thickness=3.5mm) was designed to mimic
      a bonded monolithic restoration. The ceramic discs were etched, silanized and
      luted (Variolink N) into a dentin analogue material. Fatigue failure load was
      determined using the Staircase method (100,000 cycles at 20Hz; initial fatigue
      load ~60% of the mean monotonic load-to-failure; step size ~5% of the initial
      fatigue load). A stainless-steel piston (phi=40mm) applied the load into the
      center of the specimens submerged in water. Fractographic analysis and Finite
      Element Analysis (FEA) were also performed. RESULTS: The ceramic thickness
      influenced the fatigue failure load for both ZLS materials: Suprinity (716N up to
      1119N); Celtra (404N up to 1126N). FEA showed that decreasing ceramic thickness
      led to higher stress concentration on the cementing interface. SIGNIFICANCE:
      Different ZLS glass-ceramic thicknesses influenced the fatigue failure load of
      the bonded system (i.e. the thicker the glass ceramic is, the higher the fatigue
      failure load will be). Different microstructures of the ZLS glass-ceramics might
      affect the fatigue behavior. FEA showed that the thicker the glass ceramic is,
      the lower the stress concentration at the tensile surface will be.

PMID- 29588078
TI  - Pulsed-Doppler evaluation of renal perfusion during pulsatile extracorporeal
      circulation. A pilot study.
AB  - INTRODUCTION: Acute renal failure (ARF) after cardiac surgery is a risk factor
      associated with mortality and use of resources. Some studies have reported
      beneficial effects of pulsatile flow on cardiopulmonary bypass (CPB) on renal
      function. The aim of this study is to describe the echographic morphology of the
      renal arterial wave modifying the parameters of pulsatile CPB. MATERIAL AND
      METHOD: Descriptive study was performed on 10 patients without previous AFR and
      undergoing cardiac surgery with CPB. Pre-, intra- and post-surgery renal
      ultrasound was performed. During pulsatile CPB, the amplitude and the baseline
      flow were modified. Recordings of pulsed Doppler in intrarenal arteries were
      obtained by measuring maximum systolic velocity, minimum diastolic velocity,
      resistance index (RI) and acceleration time (AT). RESULTS: Statistical
      differences were found in ultrasounds pre-CPB between A50F50 modality (P=.013),
      A50F30 (P=.013) and A60F50 (P=.003). No statistically significance was found with
      A30F30 modality (P=.125). CONCLUSIONS: The decrease in the amplitude and the
      baseline flow of pulsatility during CPB shows a renal ultrasound morphology that
      is more similar to the physiological one. Subsequent studies using these
      characteristics during pulsatile CPB could thus show perfusion over the ARF that
      occurs after cardiac surgery.

PMID- 29588080
TI  - Getting to the root of the problem.

PMID- 29588079
TI  - Risk of Cardiovascular Disease and Venous Thromboembolism Among Patients With
      Incident ANCA-Associated Vasculitis: A 20-Year Population-Based Cohort Study.
AB  - OBJECTIVE: To assess the cardiovascular disease (CVD) and venous thromboembolism
      (VTE) risks among patients with newly diagnosed antineutrophil cytoplasmic
      antibodies (ANCA)-associated vasculitis (AAV). PATIENTS AND METHODS: A population
      based incident AAV cohort of 58 patients diagnosed between 1996 and 2015 in
      Olmsted County, MN, was identified by medical record review. For each patient, 3
      age- and sex-matched non-AAV comparators were randomly selected from the same
      population and assigned an index date corresponding to the AAV incidence date.
      Medical records of cases and comparators were reviewed for CVD events, which
      included cardiac events (coronary artery disease, heart failure, and atrial
      fibrillation), cerebrovascular accidents (CVA), peripheral vascular disease
      (PVD), and VTE, which included deep vein thrombosis (DVT) and pulmonary embolism
      (PE). RESULTS: Baseline total cholesterol, high-density lipoprotein, and current
      smoking rate were lower in AAV than in comparators (P=.03, P=.01, and P=.04,
      respectively), whereas other CVD risk factors and Framingham risk score were not
      significantly different between the 2 groups. The CVD events developed in 13
      patients and 17 comparators, corresponding to a more than 3-fold increased risk
      (hazard ratio [HR], 3.15; 95% CI, 1.51-6.57). By subtypes, risks were increased
      for cardiac events (HR, 2.96; 95% CI, 1.42-6.15) and CVA (HR, 8.16; 95% CI, 2.45
      27.15), but not for PVD. The HR for VTE was 3.26 (95% CI, 0.84-12.60),
      significantly increased for DVT (HR, 6.25; 95% CI, 1.16-33.60), but not for PE
      (HR, 1.33; 95% CI, 0.23-7.54). CONCLUSION: Despite a similar prevalence of CVD
      risk factors at baseline, the risk of CVD is more than 3-fold higher and for CVA
      8-fold higher in patients with incident AAV than in matched comparator subjects.

PMID- 29588081
TI  - Dedicated cardiac intensive care units: Good for the patient, good for the
      surgeon.

PMID- 29588082
TI  - Rapid deployment aortic valve replacement devices: Too many unanswered questions.

PMID- 29588083
TI  - Leg deformation during imaginal ecdysis in the downy emerald, Cordulia aenea
      (Odonata, Corduliidae).
AB  - A dragonfly larva migrates from the water to the shore, perches on a plant stem
      and grasps it with strongly flexed legs. Adult legs inside the larval exoskeleton
      fit to the larval legs joint-to-joint. The adult emerges with stretched legs.
      During the molt, an imaginal leg must follow all the angles in exuvial joints. In
      turn, larval apodemes are withdrawn from imaginal legs. We visualized transient
      shapes of the imaginal legs by the instant fixation of insects at different
      moments of the molt, photographed isolated exuvial legs with the imaginal legs
      inside and then removed the exuvial sheath. Instant shapes of the imaginal tibia
      show sharp intrapodomere bends copying the angle in the larval femoro-tibial
      joint. The site of bending shifts distad during the molt. This is possible if the
      imaginal leg is pliable. The same problem of leg squeezing is also common in
      hemimetabolous insects as well as in other arthropods, whereas holometabolous
      insects overcome problems of a tight confinement either by using leg pliability
      in other ways but not squeezing (cyclorrhaphan flies, mosquitoes) or by pulling
      hardened legs out without change of their pupal zigzag configuration (moths,
      ants, honey bees). The pupal legs are not intended to grasp any external
      substrate.

PMID- 29588084
TI  - Hepatopulmonary Syndrome and Diffuse Interstitial Lung Disease: An Unusual
      Combination.

PMID- 29588085
TI  - Microcytic anemia due to ileocolic anastomotic ulcer.

PMID- 29588086
TI  - Is the monocyte to high-density lipoprotein cholesterol ratio important in risk
      stratification after myocardial infarction?

PMID- 29588087
TI  - Mechanism and management of cancer-associated thrombosis.
AB  - Thromboembolism is considered to have a substantial impact on outcomes in
      patients with cancer. Although progress in cancer therapy and the advent of new
      anticancer agents such as molecular targeted drugs have improved the outcomes of
      patients with cancer, the incidence of cancer-therapy-related thromboembolism is
      increasing, and the management of this adverse reaction has become a major
      problem. Cancer is intimately related to thrombosis. Thrombus formation results
      from the complex interaction of various factors, such as tissue factors,
      coagulation abnormalities, activated platelet activation, activated adhesion
      activation, and endothelial cell dysfunction. Thrombosis has an impact on cancer
      proliferation and extension. The condition known as "cancer-related thrombosis"
      must therefore be managed differently from thrombosis in patients without cancer.

PMID- 29588088
TI  - The etiologic relation between disequilibrium and orthostatic intolerance in
      patients with myalgic encephalomyelitis (chronic fatigue syndrome).
AB  - BACKGROUND: Orthostatic intolerance (OI) causes a marked reduction in the
      activities of daily living in patients with myalgic encephalomyelitis (ME) or
      chronic fatigue syndrome. Most symptoms of OI are thought to be related to
      cerebral hypo-perfusion and sympathetic activation. Because postural stability is
      an essential element of orthostatic tolerance, disequilibrium may be involved in
      the etiology of OI. METHODS AND RESULTS: The study comprised 44 patients with ME
      (men, 11 and women, 33; mean age, 37+/-9 years), who underwent neurological
      examinations and 10-min standing and sitting tests. Symptoms of OI were detected
      in 40 (91%) patients and those of sitting intolerance were detected in 30 (68%).
      Among the 40 patients with OI, disequilibrium with instability on standing with
      their feet together and eyes shut, was detected in 13 (32.5%) patients and
      hemodynamic dysfunction during the standing test was detected in 19 (47.5%); both
      of these were detected in 7 (17.5%) patients. Compared with 31 patients without
      disequilibrium, 13 (30%) patients with disequilibrium more prevalently reported
      symptoms during both standing (100% vs. 87%, p=0.43) and sitting (92% vs. 58%,
      p=0.06) tests. Several (46% vs. 3%, p<0.01) patients failed to complete the 10
      min standing test, and some (15% vs. 0%, p=0.15) failed to complete the 10-min
      sitting test. Among the seven patients with both hemodynamic dysfunction during
      the standing test and disequilibrium, three (43%) failed to complete the standing
      test. Among the 6 patients with disequilibrium only, 3 (50%) failed while among
      the 12 patients with hemodynamic dysfunction only, including 8 patients with
      postural orthostatic tachycardia, none (0%, p=0.02) failed. CONCLUSIONS: Patients
      with ME and disequilibrium reported not only OI but also sitting intolerance.
      Disequilibrium should be recognized as an important cause of OI and appears to be
      a more influential cause for OI than postural orthostatic tachycardia in patients
      with ME.

PMID- 29588089
TI  - An international comparison of risk factors between two regions with distinct
      differences in asthma prevalence.
AB  - BACKGROUND AND PURPOSE: Investigation of the geographic variation in asthma
      prevalence can improve our understanding of asthma etiology and management. The
      purpose of our investigation was to compare the prevalence of asthma and wheeze
      among adolescents living in two distinct international regions and to investigate
      reasons for observed differences. METHODS: A cross-sectional survey of 13-14 year
      olds was completed in Saskatoon, Canada (n=1200) and Skopje, Republic of
      Macedonia (n=3026), as part of the International Study of Asthma and Allergies in
      Childhood (ISAAC) Phase 3 study. Surveys were self-completed by students
      following the ISAAC protocol. Multiple logistic regression models were used to
      investigate associations with reports of asthma and current wheeze. A mediation
      analysis was then completed. RESULTS: Asthma prevalence was much higher in
      Saskatoon than Skopje (21.3% vs. 1.7%) as was the prevalence of current wheeze
      (28.2% vs. 8.8%). Higher paracetamol (acetaminophen) use was a consistent risk
      factor for asthma and wheeze in both locations and showed dose-response
      relationships. In both countries, paracetamol use and physical activity mediated
      some of the association for both asthma and wheeze. In Saskatoon, among those
      with current wheeze, 42.6% reported ever having a diagnosis of asthma compared to
      10.2% among Skopje adolescents. CONCLUSIONS: The results suggest that the
      variation in risk factors between the two locations may explain some of the
      differences in the prevalence of asthma and wheeze between these two study sites.
      However, diagnostic labeling patterns should not be ruled out as another
      potential explanatory factor.

PMID- 29588091
TI  - Traditional body mass index cut-offs in older people: Time for a rethink with
      altered fat distribution, sarcopenia and shrinking height.

PMID- 29588090
TI  - [Influenza vaccination and cystic fibrosis. Impact of an incentivisation campaign
      about influenza vaccination for patients attending the Dunkerque cystic fibrosis
      treatment centre and their health care workers].
AB  - INTRODUCTION: The main aim of this study is to evaluate the effectiveness of
      preventive actions regarding influenza in the studied populations. The secondary
      objective is to analyze and understand the mechanisms which bring about a
      behavioural change regarding influenza vaccination. METHODS: The interventional
      and prospective study was undertaken in the form of an anonymous questionnaire
      about influenza vaccination coverage and about the reasons for vaccinating or not
      vaccinating. The studied populations were patients followed for cystic fibrosis
      (n=67) in the Dunkerque cystic fibrosis treatment centre and their health care
      workers (n=117), before (April 2014) and after (April 2015) an information
      campaign and primary prevention actions (vaccination in the workplace with
      expanded time slots) in collaboration with the department of occupational
      medicine. RESULTS: In 2015, the vaccination coverage rate of health care workers
      rose to 65.63%, that is to say 2.38 times more than in 2014 (27.55%). This
      difference is significant (chi2[1]=29.17, P<0.0001). However, no significant
      difference between 2014 and 2015 was observed among patients (children and
      adults) (chi2[1]=0.24, NS) whose vaccination coverage was already optimal before
      the study. CONCLUSIONS: Raising awareness among health care workers about
      vaccination against influenza increases the coverage rate and decreases outbreaks
      of virus infection in the care services and among patients at risk. Three main
      levers were identified: the necessity of providing information on influenza
      vaccination to health care workers, the ease of vaccination access and the
      attitude towards vaccination of supervisory staff (health executives/doctors).

PMID- 29588093
TI  - Sentinel lymph node biopsy in ovarian cancers: Are intracervical injections
      necessary?

PMID- 29588094
TI  - Exploiting interfacial phenomena in organic bioelectronics: Conformable devices
      for bidirectional communication with living systems.
AB  - A novel fully organic bioelectronic device is presented and validated as
      electronic transducer and current stimulator for brain implants. The device
      integrates polymeric electrodes made of poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on paper thin foils,
      resulting in a high surface-to-volume ratio architecture that exhibits high
      sensitivity to interfacial ionic transport phenomena. The prototyping technique
      herein presented yields devices for the bidirectional communication with
      biological systems whose dimensionality can be controlled according to the
      desired application. Transduction of ultra-low local-field potentials and
      delivery of voltage pulse-trains alike those used in deep-brain stimulation are
      herein assessed, paving the way towards novel theranostic strategies for the
      treatment of Parkinson's Disease and other severe neurodegenerative and/or
      traumatic pathologies of the central nervous system.

PMID- 29588095
TI  - The utilization of automated external defibrillators in Taiwan.
AB  - BACKGROUND: Increasing attention to care of patient succumbed to out-of-hospital
      cardiac arrest (OHCA) and evidence for improved survival have resulted in many
      countries to encourage the use automated external defibrillators (AEDs) by
      legislation. In Taiwan, the amendment of the Emergency Medical Services Act
      mandated the installation of AEDs in designated areas in 2013. Since then, 6151
      AEDs have been installed and registered in mandated and non-mandated locations.
      The purpose of this study was to investigate the utilization of AEDs at mandated
      and non-mandated locations. METHODS: This paper analyzed 217 cases in whom AEDs
      was used between July 11, 2013 and July 31, 2015. Descriptive statistics were
      used to analyze the data. RESULTS: The highest frequency of AEDs used was in long
      term care facilities, accounting for 34 (15.7%) cases. The second and third
      highest was in schools and commuting stations. The highest utilization rate of
      registered AED was in long-term care facilities (73.9%), the second was in
      residential areas, and the third was in hot spring areas. Employees at the
      designated locations or medical personnel operated the AED in 143 cases (84.6%),
      and bystanders, relatives, friends or others operated the AEDs in 26 cases
      (15.4%). On-site Return of Spontaneous Circulation (ROSC) after applying AEDs
      occurred in 76 cases (45.8%). CONCLUSIONS: Long-term care facilities had the
      highest utilization of AEDs and government should pay more attention to enforce
      the installing of AEDs in these places. The government also needs to promote the
      education public on how to search the AEDs locations.

PMID- 29588096
TI  - No association of CYP2E1 genetic polymorphisms with alcohol dependence in Han
      Taiwanese population.
AB  - Cytochrome P450 2E1 (CYP2E1) gene is one of the candidate genes for alcohol
      dependence (AD). Four single nucleotide polymorphisms (SNPs) of CYP2E1 gene
      (CYP2E1*1D, *5B, *6 and *1B) have been associated with AD previously in other
      ethnic populations. To date, only CYP2E1*5B and *6 SNPs have been investigated in
      relation to AD in our population. The objective of the study was to examine the
      genetic associations of CYP2E1 covering the four above-noted SNPs conjointly with
      AD in Han Taiwanese population based on single SNP analysis and haplotype-based
      approach. We enrolled a total of 340 patients fulfilling DSM-IV-TR diagnostic
      criteria of AD and 319 healthy controls and genotyped them for the above four
      SNPs of CYP2E1 gene. By comparing the differences of genotype, allele, and
      pertinent haplotype frequencies, we did not support a genetic association between
      CYP2E1 and AD in Han Taiwanese either by single allele tests or haplotype-based
      analyses.

PMID- 29588097
TI  - Multi-class multi-residue analysis of veterinary drugs in meat using enhanced
      matrix removal lipid cleanup and liquid chromatography-tandem mass spectrometry.
AB  - This study presents the development and validation of a quantitation method for
      the analysis of multi-class, multi-residue veterinary drugs using lipid removal
      cleanup cartridges, enhanced matrix removal lipid (EMR-Lipid), for different meat
      matrices by liquid chromatography tandem mass spectrometry detection. Meat
      samples were extracted using a two-step solid-liquid extraction followed by pass
      through sample cleanup. The method was optimized based on the buffer and solvent
      composition, solvent additive additions, and EMR-Lipid cartridge cleanup. The
      developed method was then validated in five meat matrices, porcine muscle, bovine
      muscle, bovine liver, bovine kidney and chicken liver to evaluate the method
      performance characteristics, such as absolute recoveries and precision at three
      spiking levels, calibration curve linearity, limit of quantitation (LOQ) and
      matrix effect. The results showed that >90% of veterinary drug analytes achieved
      satisfactory recovery results of 60-120%. Over 97% analytes achieved excellent
      reproducibility results (relative standard deviation (RSD) < 20%), and the LOQs
      were 1-5 MUg/kg in the evaluated meat matrices. The matrix co-extractive removal
      efficiency by weight provided by EMR-lipid cartridge cleanup was 42-58% in
      samples. The post column infusion study showed that the matrix ion suppression
      was reduced for samples with the EMR-Lipid cartridge cleanup. The reduced matrix
      ion suppression effect was also confirmed with <15% frequency of compounds with
      significant quantitative ion suppression (>30%) for all tested veterinary drugs
      in all of meat matrices. The results showed that the two-step solid-liquid
      extraction provides efficient extraction for the entire spectrum of veterinary
      drugs, including the difficult classes such as tetracyclines, beta-lactams etc.
      EMR-Lipid cartridges after extraction provided efficient sample cleanup with easy
      streamlined protocol and minimal impacts on analytes recovery, improving method
      reliability and consistency.

PMID- 29588098
TI  - Validation and application of analytical method for glyphosate and glufosinate in
      foods by liquid chromatography-tandem mass spectrometry.
AB  - A reliable and sensitive method was developed for simultaneous determination of
      glyphosate and glufosinate in various food products by liquid chromatography
      tandem mass spectrometry. Based on extraction, derivatization with 9
      fluorenylmethylchloroformate and purification on solid phase extraction column,
      quantification was done by using isotopic-labeled analytes as internal standard
      and calibration in matrix. Good selectivity and sensitivity were achieved with a
      limit of quantification of 5 MUg/kg. The recoveries of these two pesticides
      ranged from 91% to 114% with inter-day and relative standard deviation of 3.8
      6.1% in five matrices of cereal group spiked at 5, 10, and 20 MUg/kg. An accuracy
      profile was performed for method validation, demonstrating the accuracy and
      precision of the method for the studied food groups. The verification results in
      expanded food groups indicated extensive applicability for the analysis of
      glyphosate and glufosinate. Finally, the developed method was applied to analyze
      136 food samples including milk-based baby foods from the French Agency for Food,
      Environmental and Occupational Health & Safety. Glyphosate residues were detected
      in two breakfast cereal samples (6.0 and 34 MUg/kg). Glufosinate residues were
      found in a sample of boiled potatoes (9.8 MUg/kg). No residues were detected in
      the other samples, including milk-based baby foods with limits of detection
      ranging from 1 to 2 MUg/kg. The method has been applied for routine national
      monitoring of glyphosate and glufosinate in various foods.

PMID- 29588099
TI  - High temperature multidimensional gas chromatographic approach for improved
      separation of triacylglycerols in olive oil.
AB  - Heart-cut multidimensional gas chromatographic (H/C MDGC) methods under suitable
      flow and high temperature (T) program conditions were developed to separate olive
      oil triacylglycerols (TAGs). Different column sets were selected for further
      evaluation, each with relatively short non-polar first dimension (1D) and mid
      polar second dimension (2D) columns of high T limits (350  degrees C). The 1D
      separation displayed three major groups of peaks in an area ratio of
      approximately 5:33:62 (of increasing retention), using flame ionisation detection
      (FID). Four groups of minor peaks, with 2 of them located between the major
      peaks, were also detected. The H/C fractions of the minor peaks, and sub-sampled
      regions across the major peaks eluting from the 1D outlet, were cryotrapped at
      the 2D inlet. The trapped TAGs then underwent temperature programmed 2D
      separation. Each of the 'H/C' zones generally gave 2-5 - and in some cases more -
      separated peaks of TAGs on the 2D column, under suitable flow condition and phase
      polarity that resulted in improved separation. Six sub-sampled H/Cs from various
      regions of the individual peaks from the 1D column were simultaneously trapped
      and released to 2D, resulting in apparently more than 22 individual TAG peaks.
      According to their different retention times, different TAGs were revealed within
      each of the 3 major groups, using H/C sub-sampling. A comprehensive sampling
      strategy that covers most of the 1D peaks further revealed the presence of more
      TAGs in the olive oil sample. This tandem column strategy was able to resolve
      more components than that usually observed on a single column.

PMID- 29588100
TI  - Systematic profiling and comparison of the lipidomes from Panax ginseng, P.
      quinquefolius, and P. notoginseng by ultrahigh performance supercritical fluid
      chromatography/high-resolution mass spectrometry and ion mobility-derived
      collision cross section measurement.
AB  - Lipidomics currently is still confronted with challenges from chromatographic
      separation and lipids identification. Here we report a lipidomics platform by
      integrating ultrahigh performance supercritical fluid chromatography/quadrupole
      time-of-flight mass spectrometry (UHPSFC/QTOF-MS) and collision cross section
      (CCS) measurement using ion mobility spectroscopy/time-of-flight mass
      spectrometry (IMS/QTOF-MS), aiming to enhance the profiling performance and
      identification reliability of lipids. The lipidomes extracted from three
      congeneric Panax species (P. ginseng, P. quinquefolius, and P. notoginseng) by
      methyl tert-butyl ether are comprehensively profiled and compared by use of this
      platform. A potent UHPSFC/QTOF-MS approach was developed on a 1.7-MUm particles
      packed Torus 2-PIC column using CH3OH (in CO2) as a modifier and CH3OH/0.2 mM
      ammonium acetate as the makeup liquid, enabling well resolution of six lipid
      subclasses by both positive and negative MSE modes. In contrast to the reversed
      phase chromatography, "normal-phase" like elution order and better resolution of
      polar lipids and some lipid isomers were achieved by UHPSFC separation. Pattern
      recognition chemometric analysis of 60 batches of Ginseng samples ultimately
      unveiled 24 lipid markers, of which triacylglycerols were the most important.
      Aside from the automated MS database searching against HMDB and LIPID MAPS, the
      application of CCS retrieval or CCS prediction improved lipid identification by
      reducing the possible hits. In conclusion, this integral platform can
      significantly improve the chromatographic separation and the reliability of
      lipids identification in lipidomics studies. It is the first report that
      systematically compares the lipidomic difference of three reputable Panax
      species, providing useful information for their quality control in addition to
      ginsenoside analysis.

PMID- 29588101
TI  - Front- and rear-facing horizontal sound localization results in adults with
      unilateral hearing loss and normal hearing.
AB  - Binaural hearing allows listeners to take advantage of auditory cues that are
      necessary for sound localization. Patients with asymmetric or unilateral hearing
      loss receive degraded or absent binaural cues and often demonstrate decreased
      sound localization in the horizontal plane. Given the importance of sound
      localization for everyday function, there is a need for clinically feasible
      methods to evaluate localization, particularly as validation of intervention for
      patients with unilateral hearing loss. The present study compared sound
      localization results obtained for front-facing and rear-facing soundfield systems
      and for a rear-facing head related transfer function (HRTF) system in two hearing
      groups, listeners with normal hearing and those with unilateral hearing loss.
      Results between the three systems were highly correlated and repeatable. Neither
      age nor a pure-tone average of 0.5, 1, 2 and 4 kHz correlated with localization
      performance among normal hearing participants. Among the UHL group, age and onset
      of severe to profound hearing loss were positively correlated with localization
      results; length of deafness was negatively correlated. Behavioral chance
      performance was established for localization with rear-facing HRTF and rear
      facing soundfield test systems; group mean results for unilateral hearing loss
      participants were significantly better than chance. Continued work is needed in
      developing clinically feasible evaluation methods for patients with asymmetric or
      unilateral hearing loss, particularly as the effects of treatment options are
      assessed.

PMID- 29588102
TI  - Women treated for gynaecological cancer during young adulthood - A mixed-methods
      study of perceived psychological distress and experiences of support from health
      care following end-of-treatment.
AB  - OBJECTIVE: To investigate the prevalence and predictors of cancer-related
      distress in younger women treated for gynaecological cancer, and to explore
      women's needs and experiences of psychosocial support following end-of-treatment.
      METHODS: Data were collected from 337 gynaecological cancer survivors, 19-39years
      at diagnosis, using a study-specific questionnaire and the Swedish Quality
      Register of Gynaecologic Cancer. Predictors of distress were investigated with
      multivariable logistic regression analysis. Open-ended questions were analysed
      with content analysis. RESULTS: The prevalence of cancer-related distress was 85%
      (n=286) including fear of cancer-recurrence (n=175, 61%), anxiety (n=152, 53%),
      depression (n=145, 51%), fear of death (n=91, 32%), concerns regarding sexuality
      (n=87, 34%) and fertility (n=78, 27%), and changed body image (n=78, 27%). Multi
      modal treatment (OR 2.25, 95% CI 1.13-4.49) and a history of psychological
      distress (OR 3.44, 95% CI 1.41-8.39) predicted cancer-related distress. The
      majority of women experiencing distress also reported a need for support after
      end-of-treatment (n=205, 71%). One-third of those receiving support reported the
      received support as inadequate (n=55, 34%). Eight categories described reasons
      for not seeking support, e.g., lacked strength to seek professional support and
      too busy managing every-day life and, wanted help but did not know who to turn
      to. Four categories described reasons for not receiving sought support e.g.,
      found it difficult to openly express feelings, psychosocial care was under
      dimensioned, insufficient and unprofessional. CONCLUSION: Results identify the
      importance of support and longer-term follow-up for young survivors of
      gynaecological cancer. The support needs to be organised to meet this group's
      specific needs.

PMID- 29588103
TI  - Black mother's intention to vaccinate daughters against HPV: A mixed methods
      approach to identify opportunities for targeted communication.
AB  - OBJECTIVE: The cervical cancer disparity continues to exist and has widened
      between Black and non-Hispanic White women. Human Papillomavirus (HPV) vaccines
      could potentially reduce this disparity, yet remain underused among Black female
      adolescents. We investigated psychosocial and cultural factors associated with
      Black mothers' intentions to vaccinate their daughters against HPV, and explored
      views toward a HPV vaccine mandate. METHODS: In this quantitative dominant, mixed
      methods study, cross sectional surveys (n=237) and follow-up semi-structured
      interviews (n=9) were conducted with Black mothers of daughters. A 2-step
      logistic regression determined factors associated with Black mothers' intention.
      Thematic content analysis determined emerging themes. RESULTS: Perceived
      susceptibility (p=.044), perceived barriers (p<.001), and subjective norms
      (p=.001) were significant predictors of maternal HPV vaccination intentions.
      Follow-up interviews provided insight into factors influencing mothers'
      intentions. Mothers with low intentions did not perceive their daughter to be
      currently sexually active or in near future, thus, not at HPV risk. Pediatricians
      were identified as the most influential person on maternal decision-making if
      there was a pre-existing relationship. However, many mothers had not received a
      pediatricians' recommendation for their daughters. Barriers influencing mother's
      decision-making include knowledge, daughters' age, and mistrust in pharmaceutical
      companies and physicians. Mothers were not in favor of the HPV vaccine mandate.
      CONCLUSIONS: Findings demonstrate the need to develop and evaluate physician-led
      interventions on HPV and vaccine importance, and engage these mothers in
      intervention development to build trust between physicians, researchers, and
      Black mothers to improve HPV vaccine uptake in Black female adolescents.

PMID- 29588104
TI  - EDDS as complexing agent for enhancing solar advanced oxidation processes in
      natural water: Effect of iron species and different oxidants.
AB  - The main purpose of this pilot plant study was to compare degradation of five
      microcontaminants (MCs) (antipyrine, carbamazepine, caffeine, ciprofloxacin and
      sulfamethoxazole at 100 MUg/L) by solar photo-Fenton mediated by EDDS and
      solar/Fe:EDDS/S2O82-. The effects of the Fe:EDDS ratio (1:1 and 1:2), initial
      iron species (Fe(II) or Fe(III) at 0.1 mM) and oxidizing agent (S2O82- or H2O2 at
      0.25-1.5 mM) were evaluated. The higher the S2O82- concentration, the faster MC
      degradation was, with S2O82- consumption always below 0.6 mM and similar
      degradation rates with Fe(II) and Fe(III). Under the best conditions (Fe 0.1 mM,
      Fe:EDDS 1:1, S2O82- 1 mM) antipyrine, carbamazepine, caffeine, ciprofloxacin and
      sulfamethoxazole at 100 MUg/L where 90% eliminated applying a solar energy of 2
      kJ/L (13 min at 30 W/m2 solar radiation <400 nm). Therefore, S2O82- promotes
      lower consumption of EDDS as Fe:EDDS 1:1 was better than Fe:EDDS 1:2. In photo
      Fenton-like processes at circumneutral pH, EDDS with S2O82- is an alternative to
      H2O2 as an oxidizing agent.

PMID- 29588105
TI  - [Bariatric surgery: The clinical pathway of the patient with a severe obesity
      surgery].
AB  - Bariatric surgery is developing parallel to the increasing prevalence of severe
      obesity. Patient' care is guided by professional recommendations highlighting the
      key-role of multidisciplinary team in perioperative management. The clinical
      pathway, particularly adapted for bariatric surgery, allows the optimization of
      resources allocation and healthcare planning while improving the quality and
      efficiency (performance) of healthcare. The assessment (and adjustments) of
      clinical pathways allows measuring the impact of quality of care, patients'
      outcome and the effectiveness of healthcare. Additionally, the development of a
      clinical pathway fosters multidisciplinary team cohesion around the project.

PMID- 29588106
TI  - Gastrointestinal stromal tumor (GIST) inpatient with Von Recklinghausen's
      disease.

PMID- 29588107
TI  - Proof-of-Concept Study of 3-D-Printed Mold-Guided Breast-Conserving Surgery in
      Breast Cancer Patients.
AB  - PURPOSE: In this proof-of-concept study, we proposed 3-D-printed mold-guided
      breast-conserving surgery (BCS) in breast cancer patients. PATIENTS AND METHODS:
      Pathologically confirmed and eligible breast cancer patients received magnetic
      resonance imaging examinations before BCS. The information on the shape, size,
      and location of the tumor relative to the nipple was extracted and analyzed. We
      used a 3-D printing technique to produce a mold to guide BCS for breast cancer
      patients. RESULTS: We performed 3-D-printed mold-guided BCS in 8 breast cancer
      patients. All of the patients had negative surgical margins, confirmed by
      intraoperative and postoperative pathologic examinations. CONCLUSION: The 3-D
      printed mold-guided BCS approach is a feasible way to achieve negative surgical
      margins. A prospective designed cohort study, with more patients included and a
      longer follow-up, is needed to further confirm its long-term oncologic safety.

PMID- 29588109
TI  - Mobilization of Bacteriocins during Competence in Streptococci.
AB  - Many streptococci have evolved the ability for natural genetic competence. Recent
      studies have uncovered regulatory links between competence and the production of
      antimicrobial peptides called bacteriocins in multiple streptococcal species.
      This reveals a broadly distributed strategy among streptococci to exploit
      bacteriocin-mediated killing during competence for adaptive gain.

PMID- 29588110
TI  - Serial Changes of Transmitral and Transtricuspid Pressure Gradients After
      Simultaneous Mitral and Tricuspid Ring Annuloplasty.
AB  - BACKGROUND: Although flexible-ring annuloplasty is more inclined to increase the
      transmitral gradient over time, its effect on the tricuspid annulus is unknown.
      This study was conducted to evaluate serial changes in mean pressure gradient
      (mPG) across tricuspid and mitral valves after simultaneous dual implantation of
      flexible bands. METHODS: Seventy-one patients (median age, 61.6 years; IQR: 50.8
      69.0 years) underwent simultaneous mitral/tricuspid annuloplasties using St. Jude
      Tailor rings. Serial mPGs across mitral and tricuspid valves were evaluated at
      three postoperative time points: predischarge, 3 years, and 5 years. To gauge the
      effects and clinical outcomes of prophylactic intervention, patients were
      categorised as tricuspid regurgitation (TR)>=moderate or TR<moderate. The median
      follow-up period was 125 months (IQR: 109-137 months). RESULTS: Unlike
      transmitral mPG, which increased over time (predischarge, 2.94; 3 years, 3.61; 5
      years, 3.87; p<0.0005), transtricuspid mPG did not change (predischarge, 1.65; 3
      years, 1.69; 5 years, 1.69; p=0.906). Preoperative TR grade had no impact on
      serial changes in transtricuspid mPG (TR>=moderate, p=0.542; TR<moderate,
      p=0.608). Three observed late recurrences of TR>=moderate degree displayed
      TR>=moderate at baseline, and overall mortality was higher in the TR>=moderate
      group (p=0.01). CONCLUSIONS: Flexible-band annuloplasty did not promote stenosis
      of tricuspid valves at mid-term follow-up. These findings confirm the safety of
      prophylactic tricuspid annuloplasty (via flexible band) as an adjunct to mitral
      annuloplasty.

PMID- 29588108
TI  - How to avoid the inappropriate use of antibiotics in upper respiratory tract
      infections? A position statement from an expert panel.
AB  - INTRODUCTION: Bacterial resistance burden has increased in the past years, mainly
      due to inappropriate antibiotic use. Recently it has become an urgent public
      health concern due to its impact on the prolongation of hospitalization, an
      increase of total cost of treatment and mortality associated with infectious
      disease. Almost half of the antimicrobial prescriptions in outpatient care visits
      are prescribed for acute upper respiratory infections, especially rhinosinusitis,
      otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists
      play an important role in orienting patients and non-specialists in the
      utilization of antibiotics rationally and properly in these infections.
      OBJECTIVES: To review the most recent recommendations and guidelines for the use
      of antibiotics in acute otitis media, acute rhinosinusitis, and
      pharyngotonsillitis, adapted to our national reality. METHODS: A literature
      review on PubMed database including the medical management in acute otitis media,
      acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a
      panel of specialists. RESULTS: Antibiotics must be judiciously prescribed in
      uncomplicated acute upper respiratory tract infections. The severity of clinical
      presentation and the potential risks for evolution to suppurative and non
      suppurative complications must be taken into 'consideration'. CONCLUSIONS:
      Periodic revisions on guidelines and recommendations for treatment of the main
      acute infections are necessary to orient rationale and appropriate use of
      antibiotics. Continuous medical education and changes in physicians' and
      patients' behavior are required to modify the paradigm that all upper respiratory
      infection needs antibiotic therapy, minimizing the consequences of its inadequate
      and inappropriate use.

PMID- 29588111
TI  - Number of advanced adenomas on index colonoscopy: Important risk factor for
      metachronous advanced colorectal neoplasia.
AB  - BACKGROUND/AIMS: Although the patients with multiple advanced adenomas (AA) in
      index colonoscopy may have an increased risk for subsequent advanced colorectal
      neoplasia (CRN), the current guidelines do not consider this factor. We aimed to
      compare the risk of metachronous advanced CRN according to the number of AAs.
      METHODS: A total of 2250 patients with >=1 adenoma at index colonoscopy were
      included. The patients were divided according to the number of AAs (1, 2 and >=3
      AAs). The relative and 3-year absolute risk of metachronous advanced CRN was
      compared between the AA groups. RESULTS: The relative risk of metachronous
      advanced CRN was higher in the patients with >=3 AAs than in the patients with
      one AA (16.7% vs. 6.8%, p = 0.004). The 3-year absolute risk of metachronous
      advanced CRN was higher in the patients with >=3 AAs than in the patients with 1
      2 AA (19.4% vs. 6.9%, p = 0.04). Having >=3 AAs (odds ratio, 5.42; 95% confidence
      interval 1.75-16.83) was a significant risk factor for developing advanced CRN.
      CONCLUSIONS: The risk of metachronous advanced CRN in the patients with >=3 AAs
      was higher than that in the patients with one or two AAs. More intensive
      surveillances might be needed for these patient groups.

PMID- 29588112
TI  - Regulation of Adipose Tissue Metabolism by the Endocannabinoid System.
AB  - White adipose tissue (WAT) stores excess energy as triglycerides, and brown
      adipose tissue (BAT) is specialized in dissipating energy as heat. The
      endocannabinoid system (ECS) is involved in a broad range of physiological
      processes and is increasingly recognized as a key player in adipose tissue
      metabolism. High ECS tonus in the fed state is associated with a disadvantageous
      metabolic phenotype, and this has led to a search for pharmacological strategies
      to inhibit the ECS. In this review we present recent developments that cast light
      on the regulation of adipose tissue metabolism by the ECS, and we discuss novel
      treatment options including the modulation of endocannabinoid synthesis and
      breakdown enzymes.

PMID- 29588113
TI  - Simulated learning environment experience in nursing students for paediatric
      practice.
AB  - The training of health professionals requires the acquisition of clinical skills
      in a safe and efficient manner, which is facilitated by a simulated learning
      environment (SLE). It is also an efficient alternative when there are limitations
      for clinical practice in certain areas. This paper shows the work undertaken in a
      Chilean university in implementing paediatric practice using SLE. Over eight
      days, the care experience of a hospitalized infant was studied applying the
      nursing process. The participation of a paediatrician, resident physician,
      nursing technician, and simulated user was included in addition to the use of a
      simulation mannequin and equipment. Simulation of care was integral and covered
      interaction with the child and family and was developed in groups of six students
      by a teacher. The different phases of the simulation methodology were developed
      from a pedagogical point of view. The possibility of implementing paediatric
      clinical practice in an efficient and safe way was confirmed. The experience in
      SLE was highly valued by the students, allowing them to develop different skills
      and abilities required for paediatric nursing through simulation.

PMID- 29588114
TI  - Post marathon cardiac troponin T is associated with relative exercise intensity.
AB  - OBJECTIVES: This study aimed to investigate whether measures of cardiopulmonary
      fitness and relative exercise intensity were associated with high sensitivity
      cardiac troponin T (cTnT) rise after a road marathon. METHODS: Fifty-two marathon
      runners (age 39+/-11 years, body mass 76.2+/-12.9kg, height 1.74+/-0.09m)
      attended the laboratory between 2 and 3 weeks prior to attempting the Brighton
      Marathon, UK. Running economy at 10kmh-1 (RE10) and race pace (RERP), ventilatory
      threshold (VT) and VO2max tests were completed. CTnT was measured within 48h
      prior to the marathon and within 10min of completing the marathon, using a high
      sensitivity assay. Heart rates (HR) were recorded throughout the marathon.
      RESULTS: Runners demonstrated a significant increase in cTnT over the marathon
      (pre-race 5.60+/-3.27ngL-1, post-race 74.52+/-30.39ngL-1, p<0.001). Markers of
      endurance performance such as running economy (10kmh-1 223+/-18mlkg-1km-1; race
      pace 225+/-22mlkg-1km-1), VT (38.5+/-6.4mlkg-1min-1) and VO2max (50.9+/-7.7mlkg
      1min-1) were not associated with post-race cTnT. Runners exercise intensity
      correlated with post-race cTnT (mean HR %VT 104+/-5%, r=0.50; peak HR %VT 118+/
      8%, r=0.68; peak HR %VO2max 96+/-6, r=0.60, p<0.05) and was different between the
      low, medium and high cTnT groups (p<0.05). CONCLUSIONS: CTnT increases above
      reference limits during a marathon. Magnitude of cTnT rise is related to exercise
      intensity relative to ventilatory threshold and VO2max, but not individuals'
      absolute cardiopulmonary fitness, training state or running history.

PMID- 29588115
TI  - Dual energy X-ray absorptiometry positioning protocols in assessing body
      composition: A systematic review of the literature.
AB  - OBJECTIVES: To systematically identify and assess methods and protocols used to
      reduce technical and biological errors in published studies that have
      investigated reliability of dual energy X-ray absorptiometry (DXA) for assessing
      body composition. DESIGN: Systematic review. METHODS: Systematic searches of five
      databases were used to identify studies of DXA reliability. Two independent
      reviewers used a modified critical appraisal tool to assess their methodological
      quality. Data was extracted and synthesised using a level of evidence approach.
      Further analysis was then undertaken of methods used to decrease DXA errors
      (technical and biological) and so enhance DXA reliability. RESULTS: Twelve
      studies met eligibility criteria. Four of the articles were deemed high quality.
      Quality articles considered biological and technical errors when preparing
      participants for DXA scanning. The Nana positioning protocol was assessed to have
      a strong level of evidence. The studies providing this evidence indicated very
      high test-retest reliability (ICC 0.90-1.00 or less than 1% change in mean) of
      the Nana positioning protocol. The National Health and Nutrition Examination
      Survey (NHANES) positioning protocol was deemed to have a moderate level of
      evidence due to lack of high quality studies. However, the available studies
      found the NHANES positioning protocol had very high test-retest reliability.
      Evidence is limited and reported reliability has varied in papers where no
      specific positioning protocol was used or reported. CONCLUSIONS: Due to the
      strong level of evidence of excellent test-retest reliability that supports use
      of the Nana positioning protocol, it is recommended as the first choice for
      clinicians when using DXA to assess body composition.

PMID- 29588116
TI  - Use and Risk Perception of Electronic Nicotine Delivery Systems and Tobacco in
      Pregnancy.
AB  - INTRODUCTION: Given the rapid rise in availability and use, understanding the
      perception of electronic nicotine delivery systems (ENDS) products in pregnant
      women is vital. As more women of reproductive age use these products, it is
      likely that their use during pregnancy is also increasing. This study
      investigated the use of ENDS and tobacco cigarettes, along with knowledge and
      perceptions of associated health risks in pregnant women. METHODS: A cross
      sectional survey was conducted at a university-based obstetrical clinic. A 32
      item self-administered survey was used to collect participants' knowledge, use,
      and risk perceptions of ENDS and tobacco smoking. Bivariate associations of
      demographics and ENDS user status were explored using Chi-square or Fisher's
      exact tests. Average differences in agreement with perception statements across
      ENDS user status were tested using ANOVA with Tukey's tests for multiple
      comparisons. RESULTS: Of 382 participants, 57.9% were 21-29 years old and 60.1%
      had some college or higher education. 30.3% reported using both ENDS and tobacco
      cigarettes and 11.9% were current ENDS users. The majority of participants had
      adequate knowledge about the facts and safety of ENDS and there was no difference
      across three ENDS user status groups. ENDS users perceived significantly lower
      risk of ENDS and higher benefit of using ENDS to aid quitting tobacco smoking,
      compared to non-ENDS users. The majority of participants reported that their
      healthcare providers less frequently assessed ENDS use during their prenatal
      visits, compared to tobacco cigarette use. CONCLUSIONS: There is critical need
      for healthcare providers to increase the screening for ENDS use during pregnancy
      and promote awareness of risks and benefits of ENDS in pregnant women.

PMID- 29588117
TI  - Decomposition of the population attributable fraction for two exposures.
AB  - PURPOSE: The population attributable fraction (AF) is frequently used to quantify
      disease burden attributable to exposures. AF is interpreted as the fractional
      reduction of disease events that would occur if exposures were eliminated. This
      article aims to provide a decomposition of the overall AF for two exposures into
      AFs for each of two exposures and AF for their interaction, using potential
      outcomes framework. METHODS: We provide the decomposition formula with and
      without confounders. We discuss an estimation method using standard regression
      models. We also show that these AFs without confounders can be effectively
      visualized. RESULTS: By a numerical comparison, we show that our decomposition is
      different from a previous decomposition, which does not have a causal
      interpretation if confounding exists. We illustrate the proposed decomposition
      using a large prospective cohort study data. CONCLUSIONS: When the primary
      exposure cannot be modifiable, the interventional interpretation of AF is
      difficult. Even then, if there exists an interaction between the exposure and
      another modifiable exposure, our decomposition can show what extent of the effect
      of the primary exposure can be eliminated by intervening on the modifiable
      exposure.

PMID- 29588118
TI  - Monitoring the efficacy of infant hepatitis B vaccination and revaccination in 0-
      to 8-year-old children: Protective anti-HBs levels and cellular immune responses.
AB  - Vaccination against hepatitis B virus (HBV) is recommended worldwide. The aim of
      this study was to assess the efficacy of infant hepatitis B vaccination and
      revaccination in 0- to 8-year-old children in the context of protective anti-HBs
      levels and cellular immune responses. Using a random questionnaire survey, 1695
      pre-school children were recruited as research subjects during January 2015 to
      June 2017. Blood samples were obtained to measure HBV serological markers as well
      as peripheral immunocytes. The children were divided into non-, low- and hyper-
      responsive groups (NR, LR, and HR) based on the vaccination efficacy.
      Additionally, the effect of revaccination on the NR group was evaluated at 1
      month after completion of the vaccination course. Among a total of 1695 children,
      1591 (93.86%) were infants who were followed while undergoing their primary
      course of hepatitis B vaccination at the 0-1-6 month schedule, and 1249 (79.30%)
      of them developed antibodies against HBsAg (anti-HBs) titers greater than 10
      IU/L. The results of immunocyte studies indicated that the CD8+ T cells,
      CD4+CD45RO+ T cells, CD8+CD45RA+ T cells, and T follicular helper (Tfh) cells
      increased significantly in NR compared with HR. However, lymphocytes, CD4+ T
      cells, and CD4+CD45RA+ T cells in NR were lower than that in HR. 96 of the non
      response cases showed seroprotection after revaccination among 103 cases.
      Therefore, most of the preschool children who received hepatitis B vaccine in
      infancy achieved significant seroprotection. Seroconversion rates of individuals
      revaccinated after initial vaccination failure were significantly higher than
      those after primary vaccination. Different vaccination efficacy groups showed
      significant changes in circulating immunocytes, which might be a factor affecting
      the recombinant HBV vaccine's immune effectiveness.

PMID- 29588119
TI  - Improving the immunogenicity and protective efficacy of the EtMIC2 protein
      against Eimeria tenella infection through random mutagenesis.
AB  - In recent years, directed evolution has emerged as an efficient tool to develop
      and identify novel protein variants. Eimeria tenella microneme-2 (EtMIC2) is a
      promising vaccine candidate for use against E. tenella infection; however, it
      only yields partial protection. The present study aimed to improve the
      immunogenicity and protective efficacy of EtMIC2 through random mutagenesis.
      Mutagenesis gene libraries of EtMIC2 were generated using error-prone polymerase
      chain reaction (epPCR), and the corresponding variant proteins were displayed on
      the yeast cell surface. Variant EtMIC2 proteins with high immunogenicity were
      screened through fluorescence-activated cell sorting (FACS) based on the affinity
      between polyclonal antibodies and antigens. Seven effective variant proteins were
      screened out and heterogeneously expressed in Escherichia coli as subunit
      vaccines. The protective efficacy of the variant proteins against E. tenella
      infections was then evaluated in chicken. Two variant proteins (1130 and 2119)
      displayed higher immunogenicity and protective efficacy than the wild-type EtMIC2
      protein against E. tenella infections, increasing body weight gains and
      significantly decreasing lesion scores and fecal oocyst shedding, and increasing
      sIgA antibody production and lymphocyte proliferation. These variants displayed
      potential for use in the development of subunit vaccines for coccidiosis in
      chickens. The present results also indicate that directed evolution technology is
      useful for improving the immunogenicity and protective efficacy of parasite
      antigens.

PMID- 29588121
TI  - Large Metal Heads and Highly Cross-Linked Polyethylene Provide Low Wear and
      Complications at 5-13 Years.
AB  - BACKGROUND: Highly cross-linked polyethylene (XLPE) is reported to have low rates
      of linear and volumetric wear at 10-14 years. In a prior study, larger (36 and 40
      mm) femoral heads were associated with more volumetric wear, but there were only
      12 hips with these heads. METHODS: We evaluated 107 hips (93 patients, with a
      mean age of 76 years) with one design of uncemented acetabular component, a 36
      (90 hips) or 40 mm (17 hips) metal femoral head, and one electron beam 100 kGy
      irradiated and remelted XLPE at a mean follow-up of 8 years (range 5-13 years).
      Selection of these femoral heads was based on several factors, including the
      perceived risk of dislocation, the outer diameter size of the acetabular
      component, and liner availability. Measurements of linear and volumetric wear
      were performed in one experienced laboratory by the Martell method and analyzed
      using the first-to-last method. Standard radiographs, with additional Judet
      views, were used to detect periprosthetic osteolysis. Clinical records were used
      to determine the complications of dislocation, liner fracture, and painful
      trunnion corrosion. RESULTS: For the entire cohort, the median linear wear rate
      was 0.041 mm/y (95% confidence interval, 0.031-0.057) and the median volumetric
      wear rate was 34.6 mm3/y (95% confidence interval, 31.4-53.5). With the numbers
      available, there was no difference in linear or volumetric wear between the 36
      and 40 mm head sizes. Small, asymptomatic osteolytic lesions were noted in 3 hips
      (2%). There were 3 patients (3%) with dislocation (2 early and 1 late), but these
      have not had a revision. There were no revisions for loosening, no liner
      fracture, and no patient with symptomatic trunnion corrosion. CONCLUSION: This
      acetabular component and XLPE with large metal heads had low rates of linear and
      volumetric wear. Large metal femoral heads did not lead to liner fracture,
      loosening, or symptomatic trunnion corrosion in this patient population. However,
      we recommend longer clinical follow-up studies and caution in the routine use of
      larger metal femoral heads in other, younger patient populations.

PMID- 29588120
TI  - Pediatric hospitalizations attributable to rotavirus gastroenteritis among
      Cambodian children: Seven years of active surveillance, 2010-2016.
AB  - BACKGROUND: Each year, approximately 1,066 Cambodian children under five years
      old die of diarrhea, and 51% of these deaths are due to rotavirus
      gastroenteritis. Quantifying childhood hospitalizations caused by severe
      rotavirus infections is also important in demonstrating disease burden caused by
      this virus. The objective of this study is to update and confirm the current
      burden of pediatric hospitalizations attributable to rotavirus gastroenteritis
      among Cambodian children using seven years of continuous active, prospective
      surveillance from 2010 to 2016. We also characterize the circulating rotavirus
      genotypic strains during this period. METHODS: Active surveillance for rotavirus
      gastroenteritis was conducted from January 2010 through December 2016 at a
      national hospital in Phnom Penh, Cambodia. Children <60 months of age who were
      hospitalized for acute gastroenteritis (AGE) were consented and enrolled.
      Information on gender, age, clinical characteristics, and month of onset were
      collected. Stool specimens were collected and tested by enzyme immunoassay for
      the presence of rotavirus antigen, and genotyping was performed on rotavirus test
      positive specimens to characterize predominant rotavirus strains during the
      surveillance period. RESULTS: Of 7007 children enrolled with AGE and having
      specimens collected, 3473 (50%) were attributed to rotavirus gastroenteritis. The
      majority of rotavirus hospitalizations occurred in children younger than two
      years old (92%). Year-round rotavirus transmission was observed, with seasonal
      peaks during the cooler, dry months between November and May. Genotypic trends in
      rotavirus were observed over the surveillance period; the predominant rotavirus
      strains changed from G1P[8] (2010-2012), to G2P[4] (2013-2014), the emergence of
      genotype G8P[8] in 2015, and G3P[8] in 2016. CONCLUSIONS: Rotavirus is the
      leading cause of severe acute gastroenteritis hospitalizations in Cambodian
      children under five years old, with 50% of such hospitalizations attributable to
      rotavirus. Over 90% of rotavirus hospitalizations occurred in children under 2
      years of age. Changes in the predominant rotavirus strains occurred over time
      among these unvaccinated children. This information is important to understand
      and prioritize the current potential impacts upon child health that could be
      achieved through the introduction of rotavirus vaccines in Cambodia.

PMID- 29588122
TI  - Autologous Impaction Bone Grafting for Bone Defects of the Medial Tibia Plateau
      During Primary Total Knee Arthroplasty: Propensity Score Matched Analysis With a
      Minimum of 7-Year Follow-Up.
AB  - BACKGROUND: The aims of this study were to (1) describe a novel technique for
      appropriate treatment of bone defects in medial tibial plateau grafted with
      autologous resected bone and (2) compare clinical outcomes, radiographic results,
      and survivorship of these knees with those of standard total knee arthroplasty
      (TKA) without bone defect. METHODS: We retrospectively reviewed 50 cases of
      primary TKA involving bone defects of medial tibial plateau managed with bone
      grafting for a minimum follow-up of 7 years. Autologous resected bones were used
      for bone graft after removing solid cortical bones at the defect site. After bone
      graft group was completed, one-to-one patient-matched control was accomplished
      based on propensity score matching of 50 knees. Survivorship was analyzed using
      the Kaplan-Meier method. The endpoint of survival was revision of implant.
      Clinical outcomes were also assessed including Knee Society Score and Western
      Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The mean
      follow-up was 117 months in the group with bone graft and 108 months in the group
      without bone graft. There were no significant differences in postoperative
      clinical scores and knee alignment. Nonprogressive radiolucent lines measuring <2
      mm were observed in 8 knees in the group with bone graft and 9 knees in the group
      without bone graft. During the follow-up period, 1 patient with late infection
      underwent 2-stage revision and another revision for tibial loosening occurred in
      both groups. The 10-year cumulative survival rate for revision was 96.0% in both
      groups. CONCLUSION: Our technique of management of medial tibial bone defect
      using autologous bone graft yielded desirable results based on survival rate and
      clinical outcome.

PMID- 29588123
TI  - Home Health Services Are Not Required for Select Total Hip Arthroplasty
      Candidates: Assessment and Supplementation With an Electronic Recovery
      Application.
AB  - BACKGROUND: At our institution, all postoperative total hip arthroplasty (THA)
      candidates have received home health services (HHS), consisting of visiting
      nurses, physical and occupational therapists. However, with a more
      technologically inclined patient population, electronic patient rehabilitation
      applications (EPRAs) can be used to deliver perioperative care at the comfort of
      the patient's home. The aim of this study is to investigate the clinical utility
      and economic burden associated with digital rehabilitation applications in
      primary THA recipients. METHODS: We conducted a single-center, retrospective
      review of patients operated between November 2016 and November 2017. Before
      surgery, and at the discretion of the surgeon, patients were assigned to EPRA
      with HHS or EPRA alone. Patient baseline demographics, EPRA engagement, and
      validated patient-reported outcomes (PROs) were collected (Veterans Rand 12-Item
      Health Survey [VR-12] and Hip Disability and Osteoarthritis Outcome Score Junior)
      at baseline and 12 weeks. These PRO scores were correlated with cohort
      assignments to assess noninferiority of EPRA alone. RESULTS: In total, 268
      patients received either EPRA-HHS (n = 169) or EPRA (n = 99) alone. Patients
      receiving EPRA only were on average younger (60.8 vs 65.8; P < .0001), but
      otherwise similar to patients in the EPRA-HHS cohort. EPRA-only patients
      demonstrated no differences in VR-12 (P > .05) and Hip Disability and
      Osteoarthritis Outcome Score Junior (P > .05) when compared with EPRA-HHS.
      CONCLUSION: The integration of electronic rehabilitation tools is gaining
      acceptance within the orthopedic community. Our study demonstrated that EPRA
      alone was clinically noninferior while substantially less costly than EPRA-HHS.

PMID- 29588124
TI  - Connectivity of the precuneus-posterior cingulate cortex with the anterior
      cingulate cortex-medial prefrontal cortex differs consistently between control
      subjects and first-episode psychosis patients during a movie stimulus.
AB  - BACKGROUND: Functional connectivity is altered in psychotic disorders. Multiple
      findings concentrate on the default mode network, anchored on the precuneus
      posterior cingulate cortex (PC-PCC). However, the nature of the alterations
      varies between studies and connectivity alterations have not been studied during
      an ecologically valid natural stimulus. In the present study, we investigated the
      functional and structural connectivity of a PC-PCC region, where functioning
      differentiated first-episode psychosis patients from control subjects during free
      viewing of a movie in our earlier study. METHODS: 14 first-episode psychosis
      patients and 12 control subjects were imaged with GE 3T, and 29 patients and 19
      control subjects were imaged with a Siemens Skyra 3T scanner while watching
      scenes from the movie Alice in Wonderland. Group differences in functional
      connectivity were analysed for both scanners separately and results were compared
      to identify any overlap. Diffusion tensor measures of 26 patients and 19 control
      subjects were compared for the related white matter tracts, identified by
      deterministic tractography. RESULTS: Functional connectivity was increased in
      patients across scanners between the midline regions of the PC-PCC and the
      anterior cingulate cortex-medial prefrontal cortex (ACC-mPFC). We found no group
      differences in any of the diffusion tensor imaging measures. CONCLUSIONS: Already
      in the early stages of psychosis functional connectivity between the midline
      structures of the PC-PCC and the ACC-mPFC is consistently increased during
      naturalistic stimulus.

PMID- 29588125
TI  - Increased complement component 4 (C4) gene expression in the cingulate cortex of
      rats exposed to late gestation immune activation.

PMID- 29588126
TI  - Effects of 12-month, double-blind N-acetyl cysteine on symptoms, cognition and
      brain morphology in early phase schizophrenia spectrum disorders.
AB  - BACKGROUND: Currently approved medications for schizophrenia are relatively
      ineffective for negative symptoms and cognitive impairment. N-Acetyl Cysteine
      (NAC) is a neuroprotective agent that improved general symptoms, cognitive
      impairment and negative symptoms in some but not all studies, but failed to
      improve positive symptoms in patients with schizophrenia. Progressive brain mass
      loss (PBML) has been consistently observed in early phase schizophrenia. NAC
      mitigates the deleterious effects oxidative stress, inflammation and
      glutamatergic excitotoxicity and these three pathological processes are
      hypothesized to contribute to PBML. METHODS: In this study, we assessed the
      effects NAC (3600mg/day) in a 52-week, double-blind, placebo controlled trial on
      symptoms, and cognition in early phase schizophrenia spectrum disorders (N=60).
      In the context of the clinical trial, we explored the effects of NAC on brain
      morphology. RESULTS: NAC significantly improved (time*group) PANSS total (F=14.7,
      p<0.001), negative (F=5.1, p=0.024) and disorganized thought (F=13.7, p<0.001)
      symptom scores. NAC failed to improve PANSS positive symptoms and BACS cognitive
      scores. In preliminary analyses, baseline right (r=-0.48, p=0.041) and left (r=
      0.45, p=0.018) total cortical thickness, and thickness in other cortical regions,
      were associated with NAC related improvement in PANSS total scores, but NAC, as
      compared to placebo, did not significantly impact brain morphology over the study
      treatment period. CONCLUSIONS: These results replicate some but not all previous
      findings of NAC efficacy. Preliminary results suggest that NAC's symptom effects
      may be related to structural integrity, but NAC failed to demonstrate treatment
      effects on longitudinal measures of brain morphology. ClinicalTrials.gov
      Identifier: NCT01339858.

PMID- 29588127
TI  - Severity of pain is associated with insufficient energy coverage in hospitalised
      patients: A cross-sectional study.
AB  - BACKGROUND & AIMS: The severity of pain is routinely assessed in hospitalised
      patients but the impact of pain and pain control on energy coverage has been
      poorly studied. This One-day cross-sectional observational study assessed the
      association between severity of pain and coverage of energy needs in hospitalised
      patients. METHODS: Foods provided and consumed were assessed on one day by
      dedicated dieticians for unselected hospitalised patients receiving three meals
      per day. Severity of pain was evaluated by a visual analogue scale at the
      mealtimes, averaged over the study day, and categorized as no pain, slight,
      moderate or severe pain. The coverage of energy needs was expressed in percentage
      of predicted needs. RESULTS: Among the 755 included patients, 63% reported having
      pain. Severe pain was associated with a lower energy coverage than no pain (p =
      0.001) or slight pain (p = 0.001). Insufficient energy coverage, defined as <=70%
      of predicted needs, occurred in 13% of the patients. In univariate logistic
      regressions, predictors of insufficient energy coverage were severe pain as
      compared to no pain (OR 2.38; 95% CI 1.21, 4.64) and treatment with opioid drugs
      as compared to no pain killer (OR 1.73; 95% CI 1.07, 2.79). When including sex,
      age, body mass index, treatment with analgesics and severity of pain in a
      multivariate logistic regression, severe pain more than doubled the risk of
      insufficient energy coverage (OR 2.32; CI 1.15, 4.66). CONCLUSIONS: Patients
      experiencing severe pain have a high risk of insufficient energy coverage.
      Optimal pain control is probably critical to prevent underfeeding in the
      hospital. TRIAL REGISTRATION: Identifier no NCT02463565 on
      www.ClinicalTrials.gov.

PMID- 29588128
TI  - Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative
      allosteric modulators for the beta2-adrenergic receptor.
AB  - The beta2-adrenergic receptor (beta2AR), a G protein-coupled receptor, is an
      important therapeutic target. We recently described Cmpd-15, the first small
      molecule negative allosteric modulator (NAM) for the beta2AR. Herein we report in
      details the design, synthesis and structure-activity relationships (SAR) of seven
      Cmpd-15 derivatives. Furthermore, we provide in a dose-response paradigm, the
      details of the effects of these derivatives in modulating agonist-induced beta2AR
      activities (G-protein-mediated cAMP production and beta-arrestin recruitment to
      the receptor) as well as the binding affinity of an orthosteric agonist in radio
      ligand competition binding assay. Our results show that some modifications,
      including removal of the formamide group in the para-formamido phenylalanine
      region and bromine in the meta-bromobenzyl methylbenzamide region caused dramatic
      reduction in the functional activity of Cmpd-15. These SAR results provide
      valuable insights into the mechanism of action of the NAM Cmpd-15 as well as the
      basis for future development of more potent and selective modulators for the
      beta2AR based on the chemical scaffold of Cmpd-15.

PMID- 29588130
TI  - Corrigendum to "Multiple identification of most important waterborne protozoa in
      surface water used for irrigation purposes by 18S rRNA amplicon-based
      metagenomics" [Int. J. Hygiene Environ. Health 221 (1) (2018) 102-111].

PMID- 29588131
TI  - Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel
      Experimental Model of Chronic Venous Hypertension.
AB  - OBJECTIVES: To assess protective effects of micronized purified flavonoid
      fraction (MPFF) on microcirculation in an original chronic model of hind limb
      venous hypertension with low blood flow in small animals. METHODS: Vein ligatures
      were performed on male hamsters, as follows: A-right femoral vein; A + B-right
      femoral vein and its right branch; A + C-right femoral vein and its left branch;
      A + B + C-right femoral and its right and left branches; D-external right iliac
      vein. In sham operated groups, similar vascular dissections were performed
      without ligatures. Superficial (epigastric) and central (jugular) venous pressure
      evaluations were made during a 10 week period. Hamsters subjected to A + B + C
      and D ligatures were selected for leukocyte rolling and sticking, functional
      capillary density (FCD), and venular and arteriolar diameter observations. D
      ligature was selected to evaluate pharmacological treatment efficacy. MPFF (100
      mg/kg), concomitant active flavonoids of MPFF (diosmetin, hesperidin, linarin,
      and isorhoifolin) (10 mg/kg), diosmin (100 mg/kg) or drug vehicle were
      administered orally during 2 weeks before vein ligature and 6 weeks thereafter.
      RESULTS: A, A + B and A + C models maintained venous return through collaterals.
      From the 2nd to the 10th weeks after vein ligatures, A + B + C and D models
      elicited a progressive increase of superficial venous pressure (3.83 +/- 0.65 vs.
      8.56 +/- 0.72 mmHg, p < .001 and 4.13 +/- 0.65 vs. 9.35 +/- 0.65 mmHg, p < .001,
      respectively) with significant changes to the microcirculation. As D model
      significantly increased superficial venous pressure without affecting central
      venous pressure, it was used to evaluate the long-term effects of treatment.
      Compared with vehicle, MPFF, concomitant active flavonoids of MPFF, and diosmin,
      significantly decreased leukocyte-endothelium interaction and prevented FCD
      reduction. Only MPFF significantly prevented venular enlargement as observed in
      the vehicle treated group. CONCLUSION: MPFF was more effective than diosmin in
      improving all microvascular variables. The superiority of MPFF over diosmin alone
      can be explained by the synergistic beneficial effects of the association between
      diosmin and active flavonoids of MPFF.

PMID- 29588129
TI  - Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling
      Functions.
AB  - Interorganellar contacts are increasingly recognized as central to the control of
      cellular behavior. These contacts, which typically involve a small fraction of
      the endomembrane surface, are local communication hubs that resemble synapses. We
      propose the term contactology to denote the analysis of interorganellar contacts.
      Endoplasmic reticulum (ER) contacts with mitochondria were recognized several
      decades ago; major roles in ion and lipid transfer, signaling, and membrane
      dynamics have been established, while others continue to emerge. The functional
      diversity of ER-mitochondrial (ER-mito) contacts is mirrored in their structural
      heterogeneity, with subspecialization likely supported by multiple, different
      linker-forming protein structures. The nanoscale size of the contacts has made
      studying their structure, function, and dynamics difficult. This review focuses
      on the structure of the ER-mito contacts, methods for studying them, and the
      roles of contacts in Ca2+ and reactive oxygen species (ROS) signaling.

PMID- 29588132
TI  - Epidemiology of lower extremity peripheral artery disease in veterans.
AB  - OBJECTIVE: The objective of this study was to describe the epidemiology, clinical
      features, outcomes, and predictors of mortality in veterans with peripheral
      artery disease (PAD). METHODS: We used national data from the Veterans Health
      Administration from fiscal years 2009 to 2011 to identify patients with a new
      diagnosis of PAD. Within this cohort, we describe characteristics of the
      patients, use of recommended medications, and clinical outcomes during a 3-year
      follow-up (fiscal year 2014). We used Cox proportional hazards regression to
      examine predictors of mortality and adverse limb outcomes (amputation and
      hospitalization for critical limb ischemia [CLI]) during follow-up. RESULTS: A
      total of 175,865 patients with a new diagnosis of PAD were included. The mean age
      was 69.9 years; 97.8% were male, and 67.7% were white. Nearly 77% of patients had
      hypertension, 46.5% had diabetes, 23% had chronic obstructive pulmonary disease,
      and 12.9% had renal failure. A prescription for statins was filled by 60.8%, and
      34.9% received high-intensity statins within 90 days of PAD diagnosis. At 1 year,
      2.6% underwent revascularization, 1.3% developed CLI, and 1.1% underwent
      amputation. During a median follow-up of 3.8 years, a total of 28.6% patients
      died (6.7% at 1 year), and 3.7% developed a limb outcome (2.0% at 1 year).
      Predictors of mortality included advanced age, comorbidities, and CLI or
      amputation at presentation. In contrast, prescription with statins was associated
      with lower mortality. Similar findings were present with regard to predictors of
      adverse limb outcomes, except that older age was associated with a lower risk of
      amputation or CLI. CONCLUSIONS: We found that veterans with PAD have a high
      prevalence of comorbid conditions and have a significant risk of mortality and
      limb loss. A substantial proportion of veterans with PAD are not prescribed
      recommended medications, especially statin therapy. Our data highlight important
      opportunities for improving care of veterans with PAD.

PMID- 29588134
TI  - Cardioprotective effect of cerium oxide nanoparticles in monocrotaline rat model
      of pulmonary hypertension: A possible implication of endothelin-1.
AB  - AIMS: Cerium oxide nanoparticles (CeO2NPs) have been recently introduced into the
      medical field for their antioxidant properties. The ability of CeO2NPs alone or
      in combination with spironolactone (SP) to attenuate monocrotaline (MCT)-induced
      pulmonary hypertension and associated right ventricular hypertrophy was studied
      in rats. A special emphasis was given to endothelin-1 pathway. MATERIALS AND
      METHODS: Pulmonary hypertension was induced in albino rats by a single
      subcutaneous injection of MCT (60 mg/kg). Rats received either single CeO2NPs
      therapy or combined therapy with SP for 2 weeks. KEY FINDINGS: CeO2NPs improved
      pulmonary function tests with concomitant decrease in serum endothelin-1 and
      pulmonary expression of endothelin-1 and its receptor ETAR. Besides, CeO2NPs
      diminished MCT-induced right ventricular hypertrophy and reduced cardiac
      oxidative stress and apoptosis. SIGNIFICANCE: CeO2NPs could improve pulmonary
      hypertension and associated right ventricular hypertrophy with no additive value
      for SP. Besides being an antioxidant, CeO2NPs work through endothelin-1 pathway
      to improve pulmonary hypertension.

PMID- 29588133
TI  - The association of comorbid depression with mortality and amputation in veterans
      with peripheral artery disease.
AB  - OBJECTIVE: Peripheral artery disease (PAD) is an increasing health concern with
      rising incidence globally. Previous studies have shown an association between PAD
      incidence and depression. The objective of the study was to determine the
      association of comorbid depression with PAD outcomes (amputation and all-cause
      mortality rates) in veterans. METHODS: An observational retrospective cohort of
      155,647 patients with incident PAD (2003-2014) from nationwide U.S. Veterans
      Health Administration hospitals was conducted using the national Veterans Affairs
      Corporate Data Warehouse. Depression was measured using concurrent International
      Classification of Diseases, Ninth Revision diagnosis codes 6 months before or
      after PAD diagnosis. The main outcomes were incident major amputation and all
      cause mortality. Crude associations were assessed with Kaplan-Meier plots. The
      effects of depression adjusted for covariates were analyzed using Cox
      proportional hazards models. RESULTS: Depression was present in 16% of the
      cohort, with the occurrence of 9517 amputations and 63,287 deaths (median follow
      up, 5.9 years). Unadjusted hazard ratios (HRs) of comorbid depression for
      amputations and all-cause mortality were 1.32 (95% confidence interval [CI], 1.25
      1.39) and 1.02 (95% CI, 0.99-1.04), respectively. After adjustment for covariates
      in Cox regression models, a diagnosis of comorbid depression at the time of PAD
      diagnosis was associated with a 13% higher amputation (HR, 1.13; 95% CI, 1.07
      1.19) and 17% higher mortality (HR, 1.17; 95% CI, 1.14-1.20) risk compared with
      patients with no depression. On stratification by use of antidepressants,
      depressed patients not taking antidepressants had a 42% higher risk of amputation
      (HR, 1.42; 95% CI, 1.27-1.58) compared with those without depression. Patients
      taking antidepressants for depression still had increased risk of amputation but
      only 10% higher compared with those without depression (HR, 1.10; 95% CI, 1.03
      1.17). Interestingly, patients taking antidepressants for other indications also
      had a higher risk of amputation compared with those not having depression or not
      taking antidepressants (HR, 1.08; 95% CI, 1.03-1.14). Having any diagnosis of
      depression or the need for antidepressants increased the mortality risk by 18% to
      25% in the PAD cohort compared with those without depression and not taking
      antidepressants for any other indication. CONCLUSIONS: PAD patients with comorbid
      depression have a significantly higher risk of amputation and mortality than PAD
      patients without depression. Furthermore, untreated depression was associated
      with an increased amputation risk in the PAD population, more so than depression
      or other mental illness being treated by antidepressants. The underlying
      mechanisms for causality, if any, remain to be determined. The association of
      antidepressant treatment use with amputation risk should prompt further
      investigations into possible mechanistic links between untreated depression and
      vascular dysfunction.

PMID- 29588135
TI  - Congenital Fistula of the Left Atrial Appendage.

PMID- 29588136
TI  - Outcomes After Surgical Treatment of Severe Tricuspid Regurgitation in a
      Contemporary Series.

PMID- 29588137
TI  - Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease:
      A randomized double blind placebo controlled trial.
AB  - BACKGROUND: Low serum vitamin D has been associated with metabolic syndrome and
      Non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the
      impact of vitamin D supplementation in treatment of patients with NAFLD. METHODS:
      In a double blind, randomized, placebo controlled trial patients with NAFLD were
      randomized to receive one weekly pearl of placebo, 50,000 U vitamin D3
      (cholecalciferol) pearl per week and 0.25 mg calcitriol (1,25
      dihydroxycholecalciferol) pearl per day for 3 months. RESULTS: 106 NAFLD patients
      were randomized to receive calcitriol, vitamin D3 and placebo pearls for 12 weeks
      and data for 91 patients were analyzed. After 12 weeks of treatment, serum
      alkaline phosphatase levels was significantly decreased from baseline levels in
      vitamin D and calcitriol treated groups (P < 0.05). Serum and gamma glutamyl
      transferase (GGT) level was also significantly decreased compared to the baseline
      levels after 12 weeks of treatment with vitamin D. There was no statistically
      significant difference between placebo, calcitriol, vitamin D groups in terms of
      serum aminotransferase, alkaline phosphatase, serum GGT and lipid profile (P >
      0.05). CONCLUSION: While significant reduction of serum alkaline phosphatase and
      GGT were seen with vitamin D and calcitriol supplementation from baseline levels,
      no beneficial effects was seen when comparing vitamin D, calcitriol and placebo
      groups at the end of trial.

PMID- 29588138
TI  - Effect of Eicosapentaenoic acid (EPA) supplementation on cardiovascular markers
      in patients with type 2 diabetes mellitus: A randomized, double-blind, placebo
      controlled trial.
AB  - AIMS: Cardiovascular complications are one of main cause of increased mortality
      and morbidity among Diabetes Mellitus (DM) patients. Altered metabolism of
      sulphur amino acids in diabetes reflected as increases in concentration of
      methionine and cysteine/cystine in the blood which known as a markers of
      Cardiovascular Diseases (CVD). The aim of present study was to determine the
      effect of Eicosapentaenoic acid (EPA) supplementation on sulfhydryl amino acids
      and Atherogenic Index of Plasma (AIP) in patients with type 2 DM (T2DM). METHOD:
      A randomized, double-blind, placebo-controlled clinical trial was performed in 36
      control and patients with DM. The subjects were randomly assigned to obtain 2 g/d
      EPA (n = 18) or placebo (n = 18) for 8 weeks. Fasting serum level of Cystein and
      Methionine were measured using HPLC method and atherogenic index of plasma (AIP)
      as a proxy measure of atherosclerosis was computed. RESULTS: Eight weeks
      supplementation with EPA led to significant reductions in Met (p < 0.002) and Cys
      (p < 0.001) compared with the placebo (p < 0.06). In addition, compared to
      placebo a significant reduction in AIP were seen after taking EPA (p < 0.04).
      CONCLUSION: EPA supplementation in patients with T2DM for eight weeks had
      beneficial effects on Met, Cys and AIP, which may attribute to the prevention of
      vascular complications in the T2DM patients.

PMID- 29588139
TI  - Pragmatic statistical issues in biological research: Introduction to special
      series.
AB  - This is an introduction to a special series so an abstract may not be required
      (but some verbiage is needed in this space to submit!!).

PMID- 29588140
TI  - Cochlear implant function in a patient with Jervell and Lange-Nielsen syndrome
      after defibrillation by countershock.
AB  - Jervell and Lange-Nielsen syndrome (JLNS), a rare autosomal recessive congenital
      QT prolongation syndrome, is characterized by cardiac arrhythmias, syncopal
      episodes, and profound deafness. A cochlear implant (CI) for patients with JLNS
      is expected to result in hearing improvement. Sometimes, defibrillation is
      required if a patient experiences lethal arrhythmia. In this paper, we report a
      pediatric patient with JLNS who received defibrillation after CI surgery in his
      right ear at the age of 2 years. With intensive care, the post-operative course
      was uneventful, and the patient acquired satisfactory speech and hearing
      abilities. Five years after the surgery, he underwent defibrillation because of
      the incidence of syncopal attack. Thereafter, arrhythmic syncope recurred three
      times, which necessitated defibrillation therapy. To prevent recurrence of
      cardiac arrhythmia, he underwent ICD (implantable cardioverter-defibrillator)
      implantation at the age of 11 years. At present, CI works well and provides good
      hearing, while syncopal attack is prevented by ICD. From the experience of this
      case, electronic circuit of CI is thought to tolerate emergency countershock if
      the speech processor is removed.

PMID- 29588141
TI  - Random walks on binary strings applied to the somatic hypermutation of B-cells.
AB  - Within the germinal center in follicles, B-cells proliferate, mutate and
      differentiate, while being submitted to a powerful selection: a micro
      evolutionary mechanism at the heart of adaptive immunity. A new foreign pathogen
      is confronted to our immune system, the mutation mechanism that allows B-cells to
      adapt to it is called somatic hypermutation: a programmed process of mutation
      affecting B-cell receptors at extremely high rate. By considering random walks on
      graphs, we introduce and analyze a simplified mathematical model in order to
      understand this extremely efficient learning process. The structure of the graph
      reflects the choice of the mutation rule. We focus on the impact of this choice
      on typical time-scales of the graphs' exploration. We derive explicit formulas to
      evaluate the expected hitting time to cover a given Hamming distance on the
      graphs under consideration. This characterizes the efficiency of these processes
      in driving antibody affinity maturation. In a further step we present a
      biologically more involved model and discuss its numerical outputs within our
      mathematical framework. We provide as well limitations and possible extensions of
      our approach.

PMID- 29588142
TI  - Diffusion-weighted magnetic resonance imaging is more sensitive than
      dimercaptosuccinic acid scintigraphy in detecting parenchymal lesions in children
      with acute pyelonephritis: A prospective study.
AB  - INTRODUCTION: Static renal scintigraphy is the gold standard for detection of
      inflammatory changes in the renal parenchyma in acute pyelonephritis. Our aim was
      to determine whether diffusion-weighted magnetic resonance imaging (DW-MRI) was
      comparable with static renal scintigraphy (DMSA-SRS) to demonstrate acute renal
      parenchymal lesions. OBJECTIVE: To compare 99mTc-dimercaptosuccinic acid static
      renal scintigraphy (DMSA-SRS) with diffusion-weighted magnetic resonance imaging
      (DW-MRI) for detecting acute inflammatory changes in the renal parenchyma in
      children with febrile urinary tract infection. METHODS: Thirty-one children (30
      girls) aged 3-18 years with a first episode of febrile UTI without a previously
      detected congenital malformation of the urinary tract, were prospectively
      included. DMSA-SRS and DW-MRI were performed within 5 days of diagnosis to detect
      renal inflammatory lesions. The DW-MRI examination was performed without contrast
      agent and without general anesthesia. Late examinations were performed after 6
      months using both methods to detect late lesions. RESULTS: DW-MRI confirmed acute
      inflammatory changes of the renal parenchyma in all 31 patients (100%), mostly
      unilateral. DMSA-SRS detected inflammatory lesions in 22 children (71%; p =
      0.002). The lesions were multiple in 26/31 children (84%) on DW-MRI and in 9/22
      (40%) on DMSA-SRS. At the control examination, scarring of the renal parenchyma
      was found equally by DW-MRI and DMSA-SRS in five patients (16%), three of whom
      were the same patients. The overall concordance of positive and negative late
      findings occurred in 87% of patients. There was correspondence in the anatomical
      location of acute and late lesions. DISCUSSION: The clinical significance of
      acute and late parenchymal findings on DWI-MR is yet to be determined. A
      limitation of our study is the age of the patients (older than 3 years) who are
      less sensitive to scar development; therefore, a smaller number of patients with
      scars could be analyzed during control examination. Further studies using the DW
      MRI should confirm its reliability to detect acute and late lesions in younger
      children and infants and determine the clinical consequences. CONCLUSION: DW-MRI
      has higher sensitivity for detecting acute renal inflammatory lesions and
      multifocal lesions than DMSA-SRS. The incidence of scars was low and corresponded
      with the anatomical location of acute and late lesions.

PMID- 29588143
TI  - Vascular thrombosis in pediatric kidney transplantation: Graft survival is
      possible with adequate management.
AB  - OBJECTIVE: Vascular thrombosis (VT) in pediatric kidney transplantation (KT) is a
      dreaded event that leads to graft loss in almost 100% of cases. In recent years,
      VT has become the most common cause of early graft loss. The aim of this study
      was to analyze our experience in diagnosis and treatment of VT and the impact of
      a new management protocol on patient outcome. METHODS: We conducted a
      retrospective study of 176 consecutive KT performed at our institution by the
      pediatric urology team between January 2000 and December 2015 and identified
      patients with VT. A protocol of prevention and early detection of VT was
      introduced in 2012. RESULTS: Out of 176 KT, nine cases of VT were identified
      (5.1%). The mean recipient age was 5.1 years (SD 4.9 years) and mean weight was
      22.28 kg (SD 15.6 kg). Diagnosis was intraoperative in two cases and within the
      first 24 h after surgery in the remaining seven. Immediate surgical exploration
      was performed after diagnosis in all. Of the five episodes that occurred before
      2012, all developed complete graft ischemia requiring transplantectomy. However,
      in the four cases diagnosed after 2012, graft perfusion could be restored in
      three, and abdominal wall closure with a mesh and delayed sequentially closure
      under ultrasound guidance was performed. With a follow-up of 30, 25, and 20
      months, the three recovered grafts are still functioning normally. CONCLUSIONS:
      Increased awareness and the application of a protocol for prevention, detection
      and treatment of VT in pediatric KT can prevent graft loss. Immediate surgical
      intervention is mandatory after diagnosis. Avoiding compartment syndrome with
      delayed sequential closure may be useful to improve graft survival.

PMID- 29588144
TI  - Steps towards Collective Sustainability in Biomedical Research.
AB  - The optimism surrounding multistakeholder research initiatives does not match the
      clear view of policies that are needed to exploit the potential of these
      collaborations. Here we propose some action items that stem from the integration
      between research advancements with the perspectives of patient-advocacy
      organizations, academia, and industry.

PMID- 29588145
TI  - Vitamin D deficiency and pre-eclampsia in Colombia: PREVitD study.
AB  - PURPOSE: Pre-eclampsia is a multisystem disorder characterized by new-onset
      hypertension and proteinuria during pregnancy. Pre-eclampsia remains a major
      cause of maternal death in low-income countries. Vitamin D has a very diverse
      biological role in cardiovascular diseases. This study will evaluate the
      association of vitamin D levels and relevance to pre-eclampsia. METHODS: We
      conducted a case-control study of women recruited from the GenPE (Genetics and
      Pre-eclampsia) Colombian registry. This is a multicenter case-control study
      conducted in eight Colombian cities. 25-Hydroxyvitamin D (25(OH)D) concentration
      was measured using liquid-chromatography-tandem mass spectrometry from 1013 women
      with pre-eclampsia and 1015 mothers without pre-eclampsia (controls). RESULTS:
      Fifty-two percent of women with pre-eclampsia were vitamin D deficient. The
      25(OH)D concentrations were significantly lower in the pre-eclampsia (mean 29.99
      ng/mL; 95% CI: 29.40-30.58 ng/mL) group compared to controls (mean 33.7 ng/mL;
      95% CI: 33.20-34.30 ng/mL). In the unadjusted model, maternal vitamin D
      deficiency, defined by maternal 25(OH)D concentration <30 ng/mL, was associated
      with an increased probability of suffering from pre-eclampsia (OR 2.10; 95% CI,
      1.75-2.51). After adjusting for covariates, a similarly increased probability of
      having pre-eclampsia was observed (OR 2.18; 95% CI, 1.80-2.64) among women with
      vitamin D deficiency, relative to controls. CONCLUSION: Although the results
      suggest that low maternal concentrations of 25(OH)D increase pre-eclampsia risk,
      this evidence may not be indicative of a causal association. Future studies are
      needed to confirm a definite causal relationship between concentrations of
      vitamin D and the risk of pre-eclampsia, by means of powered clinical trials.

PMID- 29588146
TI  - Jejunal pulling syndrome: A peculiar LCIG complication.

PMID- 29588147
TI  - Emergency physician resistance to a take-home naloxone program led by community
      harm reductionists.

PMID- 29588148
TI  - Spontaneous chordae tendineae rupture during peripartum.
AB  - Acute cardiopulmonary distress in pregnancy always carries exceptionally arduous
      challenge for physicians. Here we report a patient who sustained spontaneous
      chordae tendineae rupture complicated with severe mitral regurgitation and acute
      pulmonary edema during peripartum period. Probable causes of chordae tendineae
      rupture include mitral valve prolapse, infectious endocarditis, congenital heart
      disease, rheumatic heart disease, ischemic heart disease, connective tissue
      diseases, previous mitral valve surgery or pregnancy itself. The pathophysiology
      of spontaneous chordae tendineae rupture due to pregnancy remains unclear.
      However, certain physiological stress, including hormone changes related matrix
      remodeling, increased cardiac output during pregnancy or labor pain may
      precipitate to this condition. Literature reviews from previously reported cases
      showed that those who were diagnosed chordae tendineae rupture at very preterm
      period all had preterm delivery.

PMID- 29588149
TI  - [High impact pediatric journals in the back stage].

PMID- 29588150
TI  - LncRNAs in Adipose Tissue from Obese and Insulin-Resistant Subjects: New Targets
      for Therapy?

PMID- 29588151
TI  - Strength of the lower limb and trunk muscles is associated with gait speed in
      individuals with sub-acute stroke: a cross-sectional study.
AB  - OBJECTIVES: To investigate the association between measures of strength of the
      lower limb and trunk muscles and gait speed and to identify the muscle group that
      would best predict gait speed in individuals with sub-acute stroke. METHODS:
      Using a cross-sectional observational study design, forty-four individuals with
      sub-acute stroke (62 years, SD=14; 4 months, SD=1 post-stroke) were assessed. The
      evaluations were performed at a university laboratory, participants' homes, or
      community-based settings. Bilateral maximum isometric strength (hip, knee, and
      ankle flexors/extensors, hip abductors, trunk flexors/extensors, and trunk
      lateral flexors and rotators) was measured using a portable dynamometer.
      Comfortable and maximum gait speeds were measured using the 10-m walk test.
      RESULTS: Weak to moderate associations were found between measures of strength of
      the lower limb muscles and comfortable (0.36<=r<=0.53; p<0.05) and maximum
      (0.37<=r<=0.59; p<0.05) gait speeds, except for the non-paretic knee flexors and
      comfortable gait speed (p=0.06). Weak to moderate associations were also found
      between measures of strength of the trunk muscles and comfortable (0.39<=r<=0.50;
      p<0.05) and maximum (0.39<=r<=0.61; p<0.05) gait speeds. Stepwise multiple
      regression analyses revealed that the non-paretic dorsiflexors and the left
      lateral trunk flexors explained 29% and 42% of the variance in the maximum and
      comfortable gait speeds, respectively. CONCLUSIONS: The strength of the lower
      limb and trunk muscles was positively associated with comfortable and maximum
      gait speeds. The muscle strength of the non-paretic dorsiflexors and the left
      lateral trunk flexors might have a role to play in determining comfortable and
      maximum gait speeds of individuals with sub-acute stroke.

PMID- 29588152
TI  - Generation and characterization of a potent fully human monoclonal antibody
      against the interleukin-23 receptor.
AB  - Interleukin (IL)-12 and IL-23 share a common subunit (p40) and function in T
      helper (Th) 1 and Th17 immunity, respectively. Anti-IL-12/23p40 and specific anti
      IL-23 antibodies are currently in clinical use for psoriasis and undergoing
      trials for autoimmune diseases. Since expression levels of the IL-23 receptor are
      likely to be much lower than those of IL-23, an anti-IL-23 receptor antibody
      might offer greater promise in inhibiting the IL-23-IL-17 pathways involved in
      inflammatory disorders. To our knowledge, no anti-IL-23 receptor antibody has
      been trialed in clinical studies to date. This study describes the generation and
      characterization of AS2762900-00, a fully human monoclonal antibody against the
      IL-23 receptor. AS2762900-00 bound both human and cynomolgus monkey IL-23
      receptors. AS2762900-00 showed potent inhibitory effects on IL-23-induced Kit-225
      cell proliferation compared to the existing anti-IL-12/23p40 antibody,
      ustekinumab. In a single dose administration pharmacodynamics study in cynomolgus
      monkeys, 1 mg/kg of AS2762900-00 significantly inhibited (> 85%) IL-23-induced
      STAT3 phosphorylation in blood for up to 84 days. Therefore, AS2762900-00
      represents a potent novel IL-23-IL-17 pathway inhibitor with the potential to be
      developed into a new therapy for the treatment of autoimmune diseases.

PMID- 29588154
TI  - The object in hand: Social science of the syringe.

PMID- 29588153
TI  - Furaltadone suppresses IgE-mediated allergic response through the inhibition of
      Lyn/Syk pathway in mast cells.
AB  - Mast cells are critical cells that prompt various allergic response-inducing
      factors, contributing to allergic diseases. While used as an antibiotic for
      livestock, there is no study on the effect of furaltadone on allergic response.
      This study investigated the effect of furaltadone on mast cells and passive
      cutaneous anaphylaxis (PCA). Furaltadone inhibited the degranulation of mast
      cells stimulated by antigen (IC50, ~ 3.9 MUM), and also suppressed the production
      of tumor necrosis factor (TNF)-alpha and interleukin (IL)-4 in a concentration
      dependent manner. In addition, furaltadone inhibited allergic responses in an
      acute allergy animal model, PCA. Further investigation on the mechanism for these
      inhibitory effects of furaltadone found that the activities of Lyn/Syk and Syk
      dependent downstream proteins such as mitogen-activated protein (MAP) kinases
      were inhibited by furaltadone in mast cells. Taken together, this study
      demonstrates that furaltadone inhibits the activation of mast cells by antigen
      via the suppression of the Lyn/Syk pathway and ameliorates allergic responses in
      vivo.

PMID- 29588155
TI  - Identification of Immunodominant Th2-Cell Epitopes in Chinese Patients with
      Bullous Pemphigoid.
AB  - Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by
      autoantibodies targeting the juxtamembranous extracellular noncollagenous 16A
      (NC16A) domain of human collagen XVII (also known as BP180). Because T-helper
      (Th) cells are essential for antibody responses to antigens, we adopted an assay
      to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22
      overlapping peptides spanning the entire sequence of BP180-NC16A and investigated
      the reactivity of Th2 cells from patients with BP to these peptides using the
      Enzyme-Linked ImmunoSpot (ELISPOT) assay. We screened two epitope peptides, P2
      (492-506 aa: VRKLKARVDELERIR) and P5 (501-515 aa: ELERIRRSILPYGDS), and confirmed
      that these epitopes play a dominant role in stimulating CD4+ T-cell proliferation
      and Th2 IL-4 cytokine production, and activating B cells to secrete
      autoantibodies. These immunodominant epitopes are HLA-DR-restricted and were
      observed in subjects with different HLA alleles. This work contributes to
      elucidation of the epitope-mediated immunologic pathogenesis of BP, and the
      identified Th2-cell epitopes are candidates for epitope-specific therapeutic
      strategy.

PMID- 29588156
TI  - "Tumulus" stabilization of a total ossicular replacement prosthesis.
AB  - Functional failure of total ossicular replacement prostheses (TORP) is often due
      to secondary displacement, ranging from simple subluxation to prosthesis
      extrusion following recurrence of severe tympanic membrane retraction. Several
      surgical techniques have been proposed to stabilize a TORP, mostly using
      superimposed non-organic or resorbable heterologous materials. We describe a
      simple so-called "tumulus" surgical technique that limits prosthesis displacement
      and extrusion, regardless of the type of TORP, by using a few fragments of
      autologous cartilage that are always available and perfectly tolerated at no
      cost. Review of 31 cases treated by this technique did not reveal any cases of
      prosthesis displacement and only one case (3.2%) of prosthesis extrusion with
      audiometric results comparable to the best results reported in the literature.

PMID- 29588159
TI  - A brain targeting functionalized liposomes of the dopamine derivative N-3,4
      bis(pivaloyloxy)-dopamine for treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) remains one of the most common neurodegenerative
      movement disorders with limited treatment options available. A dopamine
      derivative N-3,4-bis(pivaloyloxy)-dopamine (BPD) previously developed in our
      group has demonstrated superior therapeutic outcome compared to levodopa in a PD
      mice model. To further improve the therapeutic performance of BPD, a brain
      targeted drug delivery system was designed using a 29 amino-acid peptide (RVG29)
      derived from rabies virus glycoprotein as the targeting ligand. RVG29
      functionalized liposomes (RVG29-lip) showed significantly higher uptake
      efficiency in murine brain endothelial cells and dopaminergic cells, and high
      penetration efficiency across the blood brain barrier (BBB) in vitro. In vivo and
      ex vivo distribution studies demonstrated RVG29-lip selectively distributed to
      the brain, striatum and substantia nigra. Furthermore, BPD loaded RVG29-lip (BPD
      RVG29-lip) exhibited improved therapeutic efficacy in a PD mouse model, while
      causing no obvious systemic toxicity after intravenous administration. Thus, BPD
      RVG29-lip represents a highly promising approach for the brain targeted treatment
      of PD.

PMID- 29588157
TI  - Gp2.5, the multifunctional bacteriophage T7 single-stranded DNA binding protein.
AB  - The essential bacteriophage T7-encoded single-stranded DNA binding protein is the
      nexus of T7 DNA metabolism. Multiple layers of macromolecular interactions
      mediate its function in replication, recombination, repair, and the maturation of
      viral genomes. In addition to binding ssDNA, the protein binds to DNA polymerase
      and DNA helicase, regulating their activities. The protein displays potent
      homologous DNA annealing activity, underscoring its role in recombination.

PMID- 29588158
TI  - Dynamics of E. coli single stranded DNA binding (SSB) protein-DNA complexes.
AB  - Single stranded DNA binding proteins (SSB) are essential to the cell as they
      stabilize transiently open single stranded DNA (ssDNA) intermediates, recruit
      appropriate DNA metabolism proteins, and coordinate fundamental processes such as
      replication, repair and recombination. Escherichia coli single stranded DNA
      binding protein (EcSSB) has long served as the prototype for the study of SSB
      function. The structure, functions, and DNA binding properties of EcSSB are well
      established: The protein is a stable homotetramer with each subunit possessing an
      N-terminal DNA binding core, a C-terminal protein-protein interaction tail, and
      an intervening intrinsically disordered linker (IDL). EcSSB wraps ssDNA in
      multiple DNA binding modes and can diffuse along DNA to remove secondary
      structures and remodel other protein-DNA complexes. This review provides an
      update on these features based on recent findings, with special emphasis on the
      functional and mechanistic relevance of the IDL and DNA binding modes.

PMID- 29588160
TI  - Role for primary immunosuppression with everolimus after pulmonary
      transplantation.

PMID- 29588161
TI  - Gene expression profiling scores in dual organ transplant patients are similar to
      those in heart-only recipients.
AB  - BACKGROUND: Serial gene expression profiling (GEP) may reduce the need for
      endomyocardial biopsies for detecting acute cellular rejection (ACR) after
      transplantation, but its performance in dual organ transplant recipients is
      currently unknown. METHODS: We analyzed 18 months of follow-up in a national
      cohort of 27 dual organ recipients (18 heart-kidney, 8 heart-liver, 1 heart-lung)
      matched to 54 heart-only recipients for gender, age, and time to first GEP
      (AlloMap(r)) test. ACR, antibody-mediated rejection (AMR), cytomegalovirus
      infections, biopsies, and longitudinal GEP scores were evaluated. RESULTS: During
      the first 90 days post-transplant, the mean GEP score for dual organ recipients
      was 25.2 +/- 9.1, vs. 23.5 +/- 7.7 for heart-only recipients (P = 0.48), with
      final GEP scores being 29.1 +/- 6.1 and 32.3 +/- 3.4, respectively (P = 0.34).
      GEP scores increased over time (P < 0.001) at a similar rate (P = 0.33) for both
      groups. One heart-only recipient had treated ACR (GEP score = 17). Fourteen
      subjects had cytomegalovirus infection, 8 of whom were dual-organ. During follow
      up, mean GEP score among patients with cytomegalovirus infection was 32.3,
      compared to 26.7 (p < 0.001) in patients without cytomegalovirus. Only 4 (2%) of
      233 biopsies were positive for mild AMR; all occurring in 2 heart-only recipients
      (GEP scores = 18-33). CONCLUSIONS: This largest cohort to date suggests that dual
      organ transplantation alone should not be reason to omit GEP testing from post
      transplant medical management, as the two groups' scores did not differ
      significantly. Confirming that GEP scores increase over time for heart-only and
      dual organ recipients and in the presence of cytomegalovirus infection, our work
      shows promise for the use of serial GEP testing in dual organ recipients.

PMID- 29588162
TI  - Aminochrome decreases NGF, GDNF and induces neuroinflammation in organotypic
      midbrain slice cultures.
AB  - Recent evidence shows that aminochrome induces glial activation related to
      neuroinflammation. This dopamine derived molecule induces formation and
      stabilization of alpha-synuclein oligomers, mitochondria dysfunction, oxidative
      stress, dysfunction of proteasomal and lysosomal systems, endoplasmic reticulum
      stress and disruption of the microtubule network, but until now there has been no
      evidence of effects on production of cytokines and neurotrophic factors, that are
      mechanisms involved in neuronal loss in Parkinson's disease (PD). This study
      examines the potential role of aminochrome on the regulation of NGF, GDNF, TNF
      alpha and IL-1beta production and microglial activation in organotypic midbrain
      slice cultures from P8 - P9 Wistar rats. We demonstrated aminochrome (25 MUM, for
      24 h) induced reduction of GFAP expression, reduction of NGF and GDNF mRNA
      levels, morphological changes in Iba1+ cells, and increase of both TNF-alpha, IL
      1beta mRNA and protein levels. Moreover, aminochrome (25 MUM, for 48 h) induced
      morphological changes in the edge of slices and reduction of TH expression. These
      results demonstrate neuroinflammation, as well as negative regulation of
      neurotrophic factors (GDNF and NGF), may be involved in aminochrome-induced
      neurodegeneration, and they contribute to a better understanding of PD
      pathogenesis.

PMID- 29588163
TI  - The involvement of plasmacytoid cells in HIV infection and pathogenesis.
AB  - Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that are
      specialized in type I interferon (IFN) production. pDCs are key players in the
      antiviral immune response and serve as bridge between innate and adaptive
      immunity. Although pDCs do not represent the main reservoir of the Human
      Immunodeficiency Virus (HIV), they are a crucial subset in HIV infection as they
      influence viral transmission, target cell infection and antigen presentation.
      pDCs act as inflammatory and immunosuppressive cells, thus contributing to HIV
      disease progression. This review provides a state of art analysis of the
      interactions between HIV and pDCs and their potential roles in HIV transmission,
      chronic immune activation and immunosuppression. A thorough understanding of the
      roles of pDCs in HIV infection will help to improve therapeutic strategies to
      fight HIV infection, and will further increase our knowledge on this important
      immune cell subset.

PMID- 29588164
TI  - Nitrated fatty acids in cardiovascular diseases.
AB  - Cardiovascular disease (CVD) is the leading cause of death and accounts for one
      third of disease-related mortality worldwide. Dysregulated redox mechanisms, in
      particular the formation of reactive oxygen species (ROS) play a pivotal
      pathogenetic role in CVD. Nitro-fatty acids (NO2-FAs) are electrophilic molecules
      which have a NO2-group bound to one of their olefinic carbons. They are
      endogenously formed by the reaction of reactive nitrogen species with unsaturated
      fatty acids. Basal levels of NO2-FAs are in the low nanomolar range and higher
      concentrations can be encountered under acidic (stomach) and inflammatory (e.g.
      ischemia/reperfusion) conditions. Dietary intake of polyunsaturated fatty acids
      in combination with nitrites raises circulating NO2-FAs to a clinically relevant
      level in mice. NO2-FAs undergo reversible covalent binding to cysteine residues
      and by virtue of these posttranslational protein modifications act as potent anti
      inflammatory signaling mediators via modulation of various critical pathways like
      nuclear factor E2-related factor 2 (Nrf2)- and peroxisome proliferator-activated
      receptor gamma (PPARgamma) activation, nuclear factor-kappa B (NF-kappaB)
      inhibition and hem oxygenase-1 (HO-1)- and heat shock protein (HSP) induction. In
      this review article, we summarize recent findings about the effects and
      underlying molecular mechanisms of NO2-FAs from a variety of pre-clinical
      cardiovascular disease models. The described findings suggest the potential of
      NO2-FAs to emerge as therapeutic agents with a broad range of potential clinical
      applications for CVD.

PMID- 29588165
TI  - A rare case of drug-induced hypersensitivity syndrome by pirfenidone for
      idiopathic pulmonary fibrosis.

PMID- 29588166
TI  - The iron pro-chelator BHAPI attenuates glutamate-induced oxidative stress via Wnt
      beta/catenin pathway in HT22 cells.
AB  - Disturbances in intracellular iron homeostasis are associated with brain damage
      under various neuropathological conditions. However, exposure of neuronal cells
      to classical iron chelators could interfere with physiological iron functions in
      the brain. Thus, iron pro-chelators represent a more advanced approach to exert
      strong free-iron binding capacity only under oxidative stress conditions. In the
      present study, we investigated the protective effects of an iron pro-chelator
      BHAPI [(E)-N'-(1-(2-((4- (4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2
      yl)benzyl)oxy)phenyl)ethylidene) isonicotino hydrazide] against glutamate-induced
      toxicity in neuronal HT22 cells. The results showed that BHAPI significantly
      increased cell viability, decreased lactate dehydrogenase (LDH) release,
      inhibited apoptotic cell death and reduced the activation of caspase-3 after
      glutamate treatment. This protection was accompanied by the preservation of
      mitochondrial function, as evidenced by reduced mitochondrial oxidative stress,
      attenuated lipid peroxidation and enhanced ATP generation. In addition, BHAPI
      promoted Wnt/beta-catenin signaling, which was related to destabilization of beta
      catenin destruction complex. The Wnt/beta-catenin signaling inhibitor JW74, but
      not IWP2, partially prevented the protective effects of BHAPI. In conclusion, our
      data suggested that BHAPI acted as a neuroprotective agent against glutamate
      induced toxicity, and this protection might be mediated by preservation of
      mitochondrial function and regulation of Wnt/beta-catenin pathway.

PMID- 29588167
TI  - Rationale and design of a randomized controlled trial of home-based primary care
      versus usual care for high-risk homebound older adults.

PMID- 29588168
TI  - Epidemicity thresholds for water-borne and water-related diseases.
AB  - Determining the conditions that favor pathogen establishment in a host community
      is key to disease control and eradication. However, focusing on long-term
      dynamics alone may lead to an underestimation of the threats imposed by outbreaks
      triggered by short-term transient phenomena. Achieving an effective
      epidemiological response thus requires to look at different timescales, each of
      which may be endowed with specific management objectives. In this work we aim to
      determine epidemicity thresholds for some prototypical examples of water-borne
      and water-related diseases, a diverse family of infections transmitted either
      directly through water infested with pathogens or by vectors whose lifecycles are
      closely associated with water. From a technical perspective, while conditions for
      endemicity are determined via stability analysis, epidemicity thresholds are
      defined through generalized reactivity analysis, a recently proposed method that
      allows the study of the short-term instability properties of ecological systems.
      Understanding the drivers of water-borne and water-related disease dynamics over
      timescales that may be relevant to epidemic and/or endemic transmission is a
      challenge of the utmost importance, as large portions of the developing world are
      still struggling with the burden imposed by these infections.

PMID- 29588169
TI  - The Adaptor Protein ENY2 Is a Component of the Deubiquitination Module of the
      Arabidopsis SAGA Transcriptional Co-activator Complex but not of the TREX-2
      Complex.
AB  - The conserved nuclear protein ENY2 (Sus1 in yeast) is involved in coupling
      transcription and mRNA export in yeast and metazoa, as it is a component both of
      the transcriptional co-activator complex SAGA and of the mRNA export complex TREX
      2. Arabidopsis thaliana ENY2 is widely expressed in the plant and it localizes to
      the nucleoplasm, but unlike its yeast/metazoan orthologs, it is not enriched in
      the nuclear envelope. Affinity purification of ENY2 in combination with mass
      spectrometry revealed that it co-purified with SAGA components, but not with the
      nuclear pore-associated TREX-2. In addition, further targeted proteomics analyses
      by reciprocal tagging established the composition of the Arabidopsis SAGA complex
      consisting of the four modules HATm, SPTm, TAFm and DUBm, and that several SAGA
      subunits occur in alternative variants. While the HATm, SPTm and TAFm robustly co
      purified with each other, the deubiquitination module (DUBm) appears to associate
      with the other SAGA modules more weakly/dynamically. Consistent with a homology
      model of the Arabidopsis DUBm, the SGF11 protein interacts directly with ENY2 and
      UBP22. Plants depleted in the DUBm components, SGF11 or ENY2, are phenotypically
      only mildly affected, but they contain increased levels of ubiquitinated histone
      H2B, indicating that the SAGA-DUBm has histone deubiquitination activity in
      plants. In addition to transcription-related proteins (i.e., transcript
      elongation factors, Mediator), many splicing factors were found to associate with
      SAGA, linking the SAGA complex and ongoing transcription with mRNA processing.

PMID- 29588170
TI  - Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy
      (BBIT) for glycemic control, body weight stability, and treatment satisfaction in
      patients treated using BBIT for type 2 diabetes without severe insulin
      deficiency: A randomized prospective pilot study.
AB  - AIMS: We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal)
      is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM)
      without severe insulin deficiency as determined by glucagon stimulation. METHODS:
      Fifty patients receiving BBIT were enrolled in this 24-week, prospective,
      randomized, open-labeled study. After excluding subjects with fasting C-peptide
      immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post
      glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or
      continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary
      endpoints were changes in body weight (BW), 7-point self-monitored blood glucose
      (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores.
      RESULT: The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group
      showed no change. BW was reduced in the Lira-basal group but increased in the
      BBIT group. The Lira-basal group also exhibited significantly reduced pre
      breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but
      not the BBIT group. Plasma lipids, liver function, and kidney function were not
      significantly changed in either group. CONCLUSIONS: Lira-basal therapy is
      superior to BBIT for T2DM without severe insulin deficiency. This study was
      registered with UMIN Clinical Trials Registry (UMIN000028313).

PMID- 29588171
TI  - Mechanism of adrenomedullin 2/intermedin mediated vasorelaxation in rat main
      pulmonary artery.
AB  - Adrenomedullin 2/intermedin (AM2/IMD) is a member of calcitonin related gene
      peptide family and an important nitric oxide mediated vasorelaxant in various
      vascular beds. However, the mechanism of post receptor-interaction is not clear
      and may differ depending on tissue type and species. In this study, we aimed to
      investigate the exact mechanism and the role of BKCa and calcium channels on the
      vasorelaxant effect of AM2/IMD in rat PA. Changes in the AM2/IMD-mediated
      vasorelaxation were evaluated in the presence of various inhibitors. CGRP(8-37)
      (10-6 M), L-NAME (10-4 M), ODQ (10-5 M), SQ22536 (10-4 M), H89 (10-6 M), TEA (10
      2 M), iberiotoxin (3 * 10-7 M), and verapamil (10-5 M), all partly or completely
      inhibited the vasorelaxation. The relaxation was also abolished by removal of the
      endothelium, or in KCl precontracted PAs. AM2/IMD did not elicit vasorelaxation
      in the Ca2+-free conditions. However, the vasorelaxation was not inhibited with
      AM(22-52) (10-6 M), 4-AP (3 * 10-3 M), glibenclamide (10-5 M), apamin (3 * 10-7
      M), TRAM-34 (10-5 M), and La+3 (10-4 M). AM2/IMD -induced changes in
      intracellular calcium levels and isometric force were monitored simultaneously in
      fura-2-loaded, endothelium-intact PAs. The AM2/IMD-induced increase in
      intracellular Ca2+ concentration was inhibited in the presence of iberiotoxin and
      verapamil, whereas no change was observed with La3+ incubation. Our data suggest
      that the cAMP/PKA pathway is one of the important pathways AM2/IMD-induced
      vasorelaxation. AM2/IMD acts through activation of endothelial BKCa and
      subsequently causes hyperpolarization of the endothelial cell membrane. The
      hyperpolarization induces Ca2+ influx, which leads to NO production and
      subsequent vasorelaxation.

PMID- 29588172
TI  - Short-term perception of and conditioned taste aversion to umami taste, and oral
      expression patterns of umami taste receptors in chickens.
AB  - Umami taste is one of the five basic tastes (sweet, umami, bitter, sour, and
      salty), and is elicited by l-glutamate salts and 5'-ribonucleotides. In chickens,
      the elucidation of the umami taste sense is an important step in the production
      of new feedstuff for the animal industry. Although previous studies found that
      chickens show a preference for umami compounds in long-term behavioral tests,
      there are limitations to our understanding of the role of the umami taste sense
      in chicken oral tissues because the long-term tests partly reflected post
      ingestive effects. Here, we performed a short-term test and observed agonists of
      chicken umami taste receptor, l-alanine and l-serine, affected the solution
      intakes of chickens. Using this method, we found that chickens could respond to
      umami solutions containing monosodium l-glutamate (MSG) + inosine 5'
      monophosphate (IMP) within 5 min. We also demonstrated that chickens were
      successfully conditioned to avoid umami solution by the conditioned taste
      aversion test. It is noted that conditioning to umami solution was generalized to
      salty and sweet solutions. Thus, chickens may perceive umami taste as a salty-
      and sweet-like taste. In addition, we found that umami taste receptor candidates
      were differentially expressed in different regions of the chicken oral tissues.
      Taken together, the present results strongly suggest that chickens have a sense
      of umami taste and have umami taste receptors in their oral tissue.

PMID- 29588173
TI  - PIL5 represses floral transition in Arabidopsis under long day conditions.
AB  - PHYTOCHROME INTERACING FACTOR 3 LIKE 5 (PIL5), also named PHYTOCHROME INTERACTING
      FACTOR 1 (PIF1) is an important b-HLH transcription factor in Arabidopsis
      thaliana. Here we show that mutant of pil5-1 displays early flowering phenotype.
      We demonstrate that the expressions of the major flowering promoter genes
      [FLOWERING LOCUS T (FT), SUPPRESOR OF OVEREXPRESSION OF CO 1 (SOC1), and LEAFY
      (LFY)] are upregulated in the mutant of pil5-1. There is a significant increase
      of the mRNA of PIL5 in the mutants of co2-1, ft-10, soc1-2, and lfy-4. These
      changes provide the molecular evidence that PIL5 interacts with the flowering
      regulators to control flowering time. Moreover, it is shown in our results that
      PIL5 mutation mediates the increased contents of gibberellic acid (GA). Which is
      further supported by the qRT-PCR analysis, an increased transcriptome level of
      the GA biosynthesis genes (GA3ox1, GA3ox2, GA20ox1, GA20ox2, and GA20ox3) has
      been observed in the pil5-1 mutants as compared to the wild type. Collectively,
      PIL5 is involved in floral transition interacting with flowering integrators and
      GA.

PMID- 29588175
TI  - Identification and analysis of microRNAs-mRNAs pairs associated with nutritional
      status in seasonal sheep.
AB  - Given the important role of nutritional status for reproductive performance, we
      aimed to explore the potential microRNA (miRNA)-mRNA pairs and their regulatory
      roles associated with nutritional status in seasonal reproducing sheep.
      Individual ewes were treated with and without 0.3 kg/day concentrates, and the
      body condition score, estrus rate, and related miRNAs and target genes were
      compared. A total of 261 differentially expressed miRNAs were identified,
      including 148 hypothalamus-expressed miRNAs and 113 ovary-expressed miRNAs, and
      349 target genes were predicted to be associated with nutritional status and
      seasonal reproduction in sheep. Ultimately, the miR-200b-GNAQ pair was screened
      and validated as differentially expressed, and a dual luciferase reporter assay
      showed that miR-200b could bind to the 3'-untranslated region of GNAQ to mediate
      the hypothalamic-pituitary-ovarian axis. Thus, miR-200b and its target gene GNAQ
      likely represent an important negative feedback loop, providing a link between
      nutritional status and seasonal reproduction in sheep toward enhancing
      reproductive performance and productivity.

PMID- 29588176
TI  - Modality-dependent effect of motion information in sensory-motor synchronised
      tapping.
AB  - Synchronised action is important for everyday life. Generally, the auditory
      domain is more sensitive for coding temporal information, and previous studies
      have shown that auditory-motor synchronisation is much more precise than visuo
      motor synchronisation. Interestingly, adding motion information improves
      synchronisation with visual stimuli and the advantage of the auditory modality
      seems to diminish. However, whether adding motion information also improves
      auditory-motor synchronisation remains unknown. This study compared tapping
      accuracy with a stationary or moving stimulus in both auditory and visual
      modalities. Participants were instructed to tap in synchrony with the onset of a
      sound or flash in the stationary condition, while these stimuli were perceived as
      moving from side to side in the motion condition. The results demonstrated that
      synchronised tapping with a moving visual stimulus was significantly more
      accurate than tapping with a stationary visual stimulus, as previous studies have
      shown. However, tapping with a moving auditory stimulus was significantly poorer
      than tapping with a stationary auditory stimulus. Although motion information
      impaired audio-motor synchronisation, an advantage of auditory modality compared
      to visual modality still existed. These findings are likely the result of higher
      temporal resolution in the auditory domain, which is likely due to the
      physiological and structural differences in the auditory and visual pathways in
      the brain.

PMID- 29588174
TI  - Serglycin is involved in inflammatory response in articular mouse chondrocytes.
AB  - Serglycin is expressed by a variety of cell types and mediates different
      functions in both normal and pathological conditions by interacting with
      different biological molecules, such as the CD44 receptor. Many studies suggest
      that serglycin has a crucial role in inflammatory response, but there are limited
      data on the functions of this proteoglycan in chondrocytes. In this study we
      investigated the effect of serglycin knockdown induced by a specific serglycin
      small interfering RNA (SRGN siRNA) in normal mouse chondrocytes stimulated with
      lipopolysaccharide (LPS). LPS administration in normal chondrocytes increased the
      expression of serglycin mRNA and related protein and the production of the pro
      inflammatory mediators TNF-alpha, IL-1beta, IL-6, iNOS and MMP-9, through NF-kB
      activation. In addition, a marked increased expression of CD44 after LPS
      stimulation was observed. Notably, the CD44 expression and the inflammatory
      response were significantly reduced by SRGN siRNA treatment in LPS treated
      chondrocytes. Similar results were obtained in normal mouse chondrocytes exposed
      to LPS, using a specific blocking antibody against CD44. These results indicate
      that serglycin produced in LPS-induced inflammation in normal mouse chondrocytes
      is able to modulate inflammation by interacting with CD44 receptor, suggesting a
      possible key role in the cartilage inflammation.

PMID- 29588177
TI  - A 43-year-old woman with unexplained elevation of hCG.
AB  - OBJECTIVE: This case report investigates an unusual hCG result in a woman who is
      not pregnant. PATIENT AND METHODS: A 43-year-old woman was admitted for
      recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma
      exchange (TPE) was initiated. Prior to transitioning the patient from TPE to
      immunosuppressive therapy, a serum qualitative hCG test was performed and was
      positive. Several etiologies for elevated hCG were considered and investigated,
      including heterophile antibody interference, endogenous hCG from pituitary or
      malignancy, and exogenous hCG. RESULTS: Retrospective measurement of hCG levels
      in remnant samples, including a sample obtained prior to TPE initiation,
      demonstrated that the hCG elevation occurred with plasma administration for TPE.
      Further investigation with the American Red Cross confirmed that a plasma donor
      was unknowingly pregnant and in the latter half of the first trimester at the
      time of donation, when hCG levels peak. CONCLUSION: In plasma recipients with
      unexplained hCG elevation, passive transfer of hCG from plasma should be
      considered in the differential diagnosis. Retrospective measurement of hCG in
      remnant samples obtained prior to plasma exchange can assist in confirming the
      source.

PMID- 29588178
TI  - Morphological analysis and three-dimensional reconstruction of the SMAS
      surrounding the nasolabial fold.
AB  - BACKGROUND: The superficial musculoaponeurotic system (SMAS), a structure that
      has been discussed with some controversy, has a complex morphological
      architecture. MATERIAL AND METHODS: Histological analysis was performed on tissue
      blocks of the nasolabial fold (NLF) collected postmortem from formalin-fixed
      bodies of one male and one female donor. Serial histological sections were made,
      stained and digitized. Three-dimensional reconstructions of the histological
      structures were performed. Specimen- and location-specific differences were
      determined. SEM analysis of the NLF tissue block was performed. RESULTS: The NLF
      SMAS is a fibro-muscular, three-dimensional meshwork bolstered with fat cells.
      Two SMAS structure types were identified adjacent to the NLF. The cheek SMAS
      structure showed a regular, vertical and parallel alignment of the fibrous septa,
      building a three-dimensional meshwork of intercommunicating compartments. It
      changed its morphology, condensing while transiting the NLF and passing over to
      form an irregular structure in the upper lip region. SEM analysis demonstrated
      the connection between the fibrous meshwork and the fat cells. SMAS blood
      circulation expanded subcutaneously without perforating the fibro-muscular septa.
      CONCLUSIONS: The NLF has a recognizable condensed cheek SMAS structure and
      represents the transition zone between the two SMAS types. Specimen-specific
      morphological differences necessitate individual planning and area-specific
      surgical procedures.

PMID- 29588179
TI  - Assessment of a subset of Slowly Mutating Y-STRs for forensic and evolutionary
      studies.
AB  - Y-specific short tandem repeat (Y-STR) loci display different mutation rates and
      consequently are suitable for forensic, genealogical, and evolutionary studies
      that require different levels of timelines and resolution. Recent efforts have
      focused on implementing Rapidly Mutating (RM) Y-STRs to assess male specific
      profiles. However, due to their high mutation rate their use in kinship testing
      or in phylogenetic studies may be less reliable. In the present study, a novel
      Slowly Mutating Y-STR (SM) panel, including DYS388, DYS426, DYS461 (Y-GATA-A7.2),
      DYS485, DYS525, and DYS561, has been developed and evaluated in a sample set of
      628 unrelated males from different worldwide populations. This panel is
      reproducible, sensitive, and robust for forensic applications and may be useful
      in conjunction with the common multiplexes, particularly in exclusion of kinship
      cases where minimal discrimination is reported employing the rapidly mutating Y
      STR systems. Furthermore, SM Y-STR data may be of value in evolutionary studies
      to optimize the resolution of phylogenetic relationships generated with current Y
      STR panel sets. In this study, we provide an extensive Y-STR allele and haplotype
      reference dataset for future applications.

PMID- 29588181
TI  - Spectroelectrochemical detection of microRNA-155 based on functional RNA
      immobilization onto ITO/GNP nanopattern.
AB  - We fabricated a microRNA biosensor using the combination of surface enhanced
      Raman spectroscopy (SERS) and electrochemical (EC) techniques. For the first
      time, the weaknesses of each techniques for microRNA detection was compensated by
      the other ones to give rise to the specific and wide-range detection of miR-155.
      A single stranded 3' methylene blue (MB) and 5' thiol-modified RNA (MB-ssRNA-SH)
      was designed to detect the target miR-155 and immobilized onto the gold
      nanoparticle-modified ITO (ITO/GNP). Upon the invasion of target strand, the
      double-stranded RNA transformed rapidly to an upright structure resulting in a
      notable decrease in SERS and redox signals of the MB. For the first time, by
      combination of SERS and EC techniques in a single platform we extended the
      dynamic range of both techniques from 10 pM to 450 nM (SERS: 10 pM-5 nM and EC: 5
      nM-450 nM). As well, the SERS technique improved the detection limit of the EC
      method from 100 pM to 100 fM, while the EC method covered single-mismatch
      detection which was the SERS deficiency. The fabricated single-step biosensor
      possessing a good capability of miRNA detection in human serum, could be employed
      throughout the broad ranges of biomedical and bioelectronics applications.

PMID- 29588180
TI  - Selenium versus sulfur: Reversibility of chemical reactions and resistance to
      permanent oxidation in proteins and nucleic acids.
AB  - This review highlights the contributions of Jean Chaudiere to the field of
      selenium biochemistry. Chaudiere was the first to recognize that one of the main
      reasons that selenium in the form of selenocysteine is used in proteins is due to
      the fact that it strongly resists permanent oxidation. The foundations for this
      important concept was laid down by Al Tappel in the 1960's and even before by
      others. The concept of oxygen tolerance first recognized in the study of
      glutathione peroxidase was further advanced and refined by those studying
      [NiFeSe]-hydrogenases, selenosubtilisin, and thioredoxin reductase. After 200
      years of selenium research, work by Marcus Conrad and coworkers studying
      glutathione peroxidase-4 has provided definitive evidence for Chaudiere's
      original hypothesis (Ingold et al., 2018) [36]. While the reaction of selenium
      with oxygen is readily reversible, there are many other examples of this
      phenomenon of reversibility. Many reactions of selenium can be described as "easy
      in - easy out". This is due to the strong nucleophilic character of selenium to
      attack electrophiles, but then this reaction can be reversed due to the strong
      electrophilic character of selenium and the weakness of the selenium-carbon bond.
      Several examples of this are described.

PMID- 29588182
TI  - Continuous citric acid production in repeated-fed batch fermentation by
      Aspergillus niger immobilized on a new porous foam.
AB  - The efficiency of current methods for industrial production of citric acid is
      limited. To achieve continuous citric acid production with enhanced yield and
      reduced cost, immobilized fermentation was employed in an Aspergillus niger 831
      repeated fed-batch fermentation system. We developed a new type of material
      (PAF201), which was used as a carrier for the novel adsorption immobilization
      system. Hydrophobicity, pore size and concentration of carriers were researched
      in A. niger immobilization. The efficiency of the A. niger immobilization process
      was analyzed by scanning electron microscopy. Then eight-cycle repeated fed-batch
      cultures for citric acid production were carried out over 600 h, which showed
      stable production with maximum citric acid concentrations and productivity levels
      of 162.7 g/L and 2.26 g L-1 h-1, respectively. Compared with some other
      literatures about citric acid yield, PAF201 immobilization system is 11.3% higher
      than previous results. These results indicated that use of the new adsorption
      immobilization system could greatly improve citric acid productivity in repeated
      fed-batch fermentation. Moreover, these results could provide a guideline for
      A.niger or other filamentous fungi immobilization in industry.

PMID- 29588183
TI  - HLA-G is expressed in intestinal samples of ulcerative colitis and Crohn's
      disease patients and HLA-G5 expression is differentially correlated with TNF and
      IL-10 cytokine expression.
AB  - HLA-G is an immunomodulatory molecule that can be produced by epithelial cells.
      Considering that TNF and IL-10 participate in bowel inflammatory disorders and
      that both cytokines modulate HLA-G, we evaluated HLA-G, TNF and IL-10 mRNA
      expression by qPCR and HLA-G protein levels by immunohistochemistry in two
      intestinal samples exhibiting different degree of inflammation within a patient
      suffering from Crohn's disease (CD) or ulcerative colitis (UC). Tissue HLA-G5 (P
      < 0.0001), TNF (P = 0.0004) and IL-10 (P = 0.0169) mRNA expression levels were
      higher in intestinal areas exhibiting intense inflammation compared to areas of
      low inflammation, and HLA-G protein levels were not associated with degree of
      mucosal inflammation. In CD, the expression of TNF was correlated with IL-10 in
      low inflamed areas, exhibiting a TNF:IL-10 ratio = 3, but in inflamed areas the
      ratio increased to 9-folds. In UC, the expression of TNF was correlated to IL-10,
      irrespective of the inflammation grade, with little variation of the TNF:IL-10
      ratio in the various inflamed areas. TNF and IL-10 expression was correlated with
      HLA-G5 expression in mild inflamed areas. Both CD and UC samples exhibited gene
      and protein expression of HLA-G; and the HLA-G5 expression is differentially
      correlated with TNF and IL-10 levels depending on the type of the underlying
      inflammatory bowel disorder.

PMID- 29588184
TI  - The matrices and constraints of GT/AG splice sites of more than 1000
      species/lineages.
AB  - To provide a resource for the splice sites (SS) of different species, we
      calculated the matrices of nucleotide compositions of about 38 million splice
      sites from >1000 species/lineages. The matrices are enriched of aGGTAAGT (5'SS)
      or (Y)6N(C/t)AG(g/a)t (3'SS) overall; however, they are quite diverse among
      hundreds of species. The diverse matrices remain prominent even under sequence
      selection pressures, suggesting the existence of diverse constraints as well as U
      snRNAs and other spliceosomal factors and/or their interactions with the splice
      sites. Using an algorithm to measure and compare the splice site constraints
      across all species, we demonstrate their distinct differences quantitatively. As
      an example of the resource's application to answering specific questions, we
      confirm that high constraints of particular positions are significantly
      associated with transcriptome-wide, increased occurrences of alternative splicing
      when uncommon nucleotides are present. More interestingly, the abundance of
      alternative splicing in 16 species correlates with the average constraint index
      of splice sites in a bell curve. This resource will allow users to assess
      specific sequences/splice sites against the consensus of every Ensembl-annotated
      species, and to explore the evolutionary changes or relationship to alternative
      splicing and transcriptome diversity. Web-search or update features are also
      included.

PMID- 29588185
TI  - Septic shock due to meropenem- and colistin-resistant Cupriavidus pauculus.

PMID- 29588186
TI  - The handwash station: friend or fiend?
AB  - Handwashing is a key barrier to cross-infection performed at a handwash station
      (HWS, an interface between water and drainage systems). Widespread and often
      uncritical placement/design and use of HWSs is not without attendant risks.
      Recognition of the associated hazards went unheeded for over 45 years despite
      warnings in the literature, until the neonatal outbreak of pseudomonas in Belfast
      in 2012 forced change. Minimizing risk requires a holistic approach beyond the
      mere testing of water from the outlet of a HWS for the presence of Pseudomonas
      aeruginosa or other pathogens. Literature reports of outbreaks linked to HWSs
      outside of neonatal units are over-represented by multi-resistant organisms, and
      increasingly by carbapenemase-producing organisms. Evidence suggests that a large
      proportion of waterborne transmissions go undetected. Much could be done to
      improve current design, use and placement of HWSs, and this is assessed
      critically in this article.

PMID- 29588187
TI  - Effect of chlorhexidine baths on central-line-associated bloodstream infections
      in a neonatal intensive care unit in a developing country.
AB  - Healthcare-associated infections, particularly central-line-associated
      bloodstream infections (CLABSIs), are worrisome in neonates. This study describes
      the impact of chlorhexidine baths on CLABSI rates in a neonatal intensive care
      unit in a developing country, through a quasi-experimental study undertaken over
      62 months (January 2012 to February 2017) divided into two periods: before and
      after the implementation of a protocol for chlorhexidine baths in July 2014. The
      rate of CLABSIs per 1000 central-line-days decreased from 8.64 to 4.28 after
      implementation of the protocol. The use of chlorhexidine baths appears to reduce
      the number of CLABSIs in neonates.

PMID- 29588188
TI  - 3D computer simulation analysis of the flap volume change in total tongue
      reconstruction flaps.
AB  - BACKGROUND: A decreased flap volume can be an obstacle to proper phonation and
      swallowing. In this study we verified the proportion of volume decrease using 3D
      reconstructed images and identified the contributors to flap volume loss.
      METHODS: We retrospectively analyzed all patients who underwent radical excision
      of tongue cancer and reconstructive surgery in our institution from January 2003
      to October 2016. Segmentation of the DICOM images, 3D rendering of the neotongue
      flap, and analysis of the reconstructed images were performed using SPlanner
      V1(r) software. RESULTS: The first postoperative imaging work-up was performed
      within an average of 22 days (T1). The last follow-up images were taken at an
      average of 6.25 months (T2). The mean flap volume at T2 was reduced to 82.99 per
      cent compared with T1, and flap height was reduced to 91.85 per cent, giving mean
      volume and height decreases of 17.01 per cent and 8.15 per cent, respectively.
      Neither the volume/height difference between T1 and T2 nor the flap volume/height
      discrepancy compared with the preoperative tongue affected speech or feeding
      function. The difference between the flap and preoperative tongue volumes was
      significantly related to the presence of complications (p = 0.0153). Initial flap
      volume was significantly related to the flap volume reduction (p = 0.0159).
      CONCLUSIONS: The mean flap volume reduction is the only factor significantly
      related to initial flap volume. Our realistic 3D reconstructed image and novel
      software enables us to more precisely predict the flap volume of the
      postoperative state and preoperatively evaluate the required flap size for
      covering defects.

PMID- 29588190
TI  - Optimal aspirin dosing for preeclampsia prevention.

PMID- 29588189
TI  - Podoplanin expression as a predictive marker of dysplasia in oral leukoplakia.
AB  - PURPOSE: Recent studies have emphasized the role of podoplanin in oral lesions at
      risk of malignant transformation. We investigated a group of oral leukoplakias
      (OLs) to determine a possible relation between altered podoplanin expression and
      dysplasia, and to compare the results with those obtained by other, widely used
      biomarkers. MATERIALS AND METHODS: The population consisted of 40 consecutive
      patients with a clinical and histological diagnosis of OL. Thirty-two OLs did not
      show dysplasia, whereas eight lesions presented with dysplasia.
      Immunohistochemical expression of podoplanin, p53 and Ki67 was analyzed in all
      samples. RESULTS: All three biomarkers were positive in seven of eight dysplastic
      OLs. Among the 32 OLs without dysplasia, Ki67 and p53 showed positive values in
      21 and 10 samples respectively, whereas podoplanin was positive in only one case.
      Multiple logistic regression showed that podoplanin was the most powerful
      variable (Chi square 9.77; p < .01) statistically related to the presence of
      dysplasia. In addition, podoplanin showed a higher specificity value (96.87%)
      than Ki67 (34.37%) and p53 (68.75%). CONCLUSION: Podoplanin seems to be a
      reliable means of discriminating lesions with epithelial dysplasia and could be
      introduced in routine practice as a marker to discriminate OLs at risk of
      developing cancer.

PMID- 29588191
TI  - Arachidonic acid metabolites of CYP4A and CYP4F are altered in women with
      preeclampsia.
AB  - Few studies exist on cytochrome P450 (CYP450) metabolites of arachidonic acid
      (AA) pertaining to the pathophysiological events in pregnancy. We hypothesized
      that metabolism of AA via the CYP450 pathways is altered within the placenta in
      women with preeclampsia (PE) and contributes to the pathophysiology of the
      disease. Thus, placental vascular CYP450 enzyme expression and activity were
      measured in normal pregnant (NP) and preeclamptic (PE) patients. CYP450 isoform
      expression (CYP4A11, CYP4A22, CYP4F2, and CYP4F3) was found to be elevated within
      the placenta of women with PE compared to normal pregnant (NP) women and chronic
      hypertensive (CHTN) pregnant women. In addition, placental production of 20-HETE
      was significantly increased in PE women compared to both NP and CHTN women.
      Moreover, there was an imbalance in circulating 20-HETE:EETs in PE women. To
      examine whether alterations in CYP450 AA metabolism contribute to the altered
      placentation in PE, trophoblast function, proliferation and migration were
      assessed in the presence of exogenous 20-HETE and a 20-HETE specific synthesis
      inhibitor, HET0016. Trophoblast proliferation was significantly increased in the
      presence of 20-HETE (1 MUM) and reduced with 20-HETE blockade by HET0016 (1 mM, 5
      mM, and 10 mM). On the contrary, administration of exogenous 20-HETE (1 MUM)
      significantly reduced trophoblast migration. In conclusion, metabolism of AA via
      CYP450 is altered in PE, and increased placental production of 20-HETE may
      contribute to the pathophysiology of the disease.

PMID- 29588192
TI  - Cardiovascular diseases, NLRP3 inflammasome, and western dietary patterns.
AB  - Cardiovascular diseases (CVD) are the leading cause of death worldwide, with high
      prevalence in industrialized countries. Cardiovascular risk factors are mainly
      influenced by diet, which like other lifestyle factors can be modified to either
      reduce or increase cardiovascular risk. Other metabolic diseases such as
      metabolic syndrome, type II diabetes mellitus, and obesity are associated to CVD
      and highly influenced by the diet. Inflammation has demonstrated to be a key
      factor in the biological progress of these diseases. Interestingly, IL-1beta
      which is associated to several steps in the development of atherosclerosis, heart
      disease, and the association of obesity and type II diabetes with CVD, is
      activated by the inflammasome complex, a multiprotein complex composed of an
      intracellular sensor, typically a Nod-like receptor (NLR), the precursor
      procaspase-1, and the adaptor ASC (apoptosis-associated speck-like protein
      containing a CARD. In the last years, inflammasome complex has been studied in
      depth and has been associated with the effect of unhealthy diets both from a
      clinical and experimental view point. We have reviewed the evidences supporting
      the role of the inflammasome complex in the development of cardiovascular
      pathology by unhealthy diets and the therapeutic perspectives.

PMID- 29588193
TI  - Cross-talk between endogenous H2S and NO accounts for vascular protective
      activity of the metal-nonoate Zn(PipNONO)Cl.
AB  - Nitric oxide (NO) and hydrogen sulfide (H2S) are now recognized as gaseous
      transmitters with many cardiovascular protective properties. The present study
      concerns the possibility that NO donors can also function through endogenous
      activation of NO and H2S pathways. Based on the previous characterization of a
      novel metal-nonoate, Ni(PipNONO)Cl, our aim was: 1) to study the effects of a
      zinc based compound, Zn(PipNONO)Cl, on vascular endothelial and smooth muscle
      cells, and 2) to assess the role and interplay between endogenous NO and H2S
      promoted by the nonoate. Zn(PipNONO)Cl completely reproduced the vasodilation
      elicited by Ni(PipNONO)Cl. In the presence of endothelium, preincubation with
      Zn(PipNONO)Cl sensitized the intima to acetylcholine-induced vasodilation. When
      tested on cultured endothelial cells, Zn(PipNONO)Cl prompted PI-3K/Akt- and
      MAPK/ERK1/2-mediated survival. Nitrite levels indicated fast NO release (due to
      the molecule) and delayed (1-6 h) NO production linked to PI-3K/Akt-dependent
      eNOS activation. In the same time frame (1-6 h), significant CSE-dependent H2S
      levels were detected in response to Zn(PipNONO)Cl. The mechanisms responsible for
      H2S increase seemed to depend on the NONO moiety/sGC/cGMP pathway and zinc
      associated ROS production. Our results indicate that endogenous H2S and NO were
      produced after fast NO release from Zn(PipNONO)Cl, contributing to the vascular
      endothelium protective effect. The effect was partially reproduced on smooth
      muscle cells, where Zn(PipNONO)Cl inhibited cell proliferation and migration. In
      conclusion, vasorelaxant effects, with complementary activities on endothelium
      and smooth muscle cells, are elicited by the novel metal-nonoate Zn(PipNONO)Cl.

PMID- 29588194
TI  - Using chemical bond-based method to predict site of metabolism for five
      biotransformations mediated by CYP 3A4, 2D6, and 2C9.
AB  - Although it has been proposed for decades to predict site of metabolism (SOM) by
      in silico methods, identifying SOM correctly remains an unsolved fundamental
      problem and is an active area of research. In our prior works, we proposed a
      chemical bond-based approach to construction of SOM prediction models by
      integrating chemical bond descriptors and drug-metabolizing enzymes data.
      Although it has been evaluated with both 10-fold cross-validation and independent
      validation, we believe comparisons between this method and prior methods using
      publicly accessible external datasets are indispensable and more desirable. In
      the current study, based on chemical bond-based method, metabolism data released
      by Sheridan et al. and Zaretzki et al. was utilized to establish metabolite
      prediction models for CYP450 3A4, 2D6, and 2C9. Five major reaction types were
      involved, including Aliphatic C-hydroxylation, Aromatic C-hydroxylation, N
      dealkylation, O-dealkylation, and S-Oxidation. Consequently, all our five models
      showed impressive performance on predicting SOMs, with accuracy and area under
      curve exceeded 0.940 and 0.953, respectively. Compared to prior works, our models
      were better than SOMP both in "SOM-scale" and "molecule-scale". In conclusion,
      comparisons between chemical-bond based method and prior works were conducted for
      the first time, which demonstrated that chemical-bond based method is better than
      or at least comparable to prior works.

PMID- 29588195
TI  - Simultaneous profiling of activity patterns in multiple neuronal subclasses.
AB  - BACKGROUND: Neuronal networks typically comprise heterogeneous populations of
      neurons. A core objective when seeking to understand such networks, therefore, is
      to identify what roles these different neuronal classes play. Acquiring single
      cell electrophysiology data for multiple cell classes can prove to be a large and
      daunting task. Alternatively, Ca2+ network imaging provides activity profiles of
      large numbers of neurons simultaneously, but without distinguishing between cell
      classes. NEW METHOD: We therefore developed a strategy for combining cellular
      electrophysiology, Ca2+ network imaging, and immunohistochemistry to provide
      activity profiles for multiple cell classes at once. This involves cross
      referencing easily identifiable landmarks between imaging of the live and fixed
      tissue, and then using custom MATLAB functions to realign the two imaging data
      sets, to correct for distortions of the tissue introduced by the fixation or
      immunohistochemical processing. RESULTS: We illustrate the methodology for
      analyses of activity profiles during epileptiform events recorded in mouse brain
      slices. We further demonstrate the activity profile of a population of
      parvalbumin-positive interneurons prior, during, and following a seizure-like
      event. COMPARISON WITH EXISTING METHODS: Current approaches to Ca2+ network
      imaging analyses are severely limited in their ability to subclassify neurons,
      and often rely on transgenic approaches to identify cell classes. In contrast,
      our methodology is a generic, affordable, and flexible technique to characterize
      neuronal behaviour with respect to classification based on morphological and
      neurochemical identity. CONCLUSIONS: We present a new approach for analysing Ca2+
      network imaging datasets, and use this to explore the parvalbumin-positive
      interneuron activity during epileptiform events.

PMID- 29588196
TI  - Ethanol production from sweet sorghum by Saccharomyces cerevisiae DBKKUY-53
      immobilized on alginate-loofah matrices.
AB  - Ethanol production from sweet sorghum juice (SSJ) using the thermotolerant
      Saccharomyces cerevisiae strain DBKKUY-53 immobilized in an alginate-loofah
      matrix (ALM) was successfully developed. As found in this study, an ALM with
      dimensions of 20*20*5mm3 is effective for cell immobilization due to its compact
      structure and long-term stability. The ALM-immobilized cell system exhibited
      greater ethanol production efficiency than the freely suspended cell system. By
      using a central composite design (CCD), the optimum conditions for ethanol
      production from SSJ by ALM-immobilized cells were determined. The maximum ethanol
      concentration and volumetric ethanol productivity obtained using ALM-immobilized
      cells under the optimal conditions were 97.54g/L and 1.36g/Lh, respectively. The
      use of the ALM-immobilized cells was successful for at least six consecutive
      batches (360h) without any loss of ethanol production efficiency, suggesting
      their potential application in industrial ethanol production.

PMID- 29588197
TI  - Screening of medium constituents for clavulanic acid production by Streptomyces
      clavuligerus.
AB  - Clavulanic acid is a beta-lactam compound with potent inhibitory activity against
      beta-lactamases. Studies have shown that certain amino acids play essential roles
      in CA biosynthesis. However, quantitative evaluations of the effects of these
      amino acids are still needed in order to improve CA production. Here, we report a
      study of the nutritional requirements of Streptomyces clavuligerus for CA
      production. Firstly, the influence of the primary nitrogen source and the salts
      composition was investigated. Subsequently, soybean protein isolate was
      supplemented with arginine (0.0-3.20gL-1), threonine (0.0-1.44gL-1), ornithine
      (0.0-4.08gL-1), and glutamate (0.0-8.16gL-1), according to a two-level central
      composite rotatable design. A medium containing ferrous sulfate yielded CA
      production of 437mgL-1, while a formulation without this salt produced only 41mgL
      1 of CA. This substantial difference suggested that Fe2+ is important for CA
      biosynthesis. The experimental design showed that glutamate and ornithine
      negatively influenced CA production while arginine and threonine had no
      influence. The soybean protein isolate provided sufficient C5 precursor for CA
      biosynthesis, so that supplementation was unnecessary. Screening of medium
      components, together with experimental design tools, could be a valuable way of
      enhancing CA titers and reducing the process costs.

PMID- 29588198
TI  - Identification of enteric viruses circulating in a dog population with low
      vaccine coverage.
AB  - Although the use of vaccines has controlled enteric diseases in dogs in many
      developed countries, vaccine coverage is still under optimal situation in Brazil.
      There is a large population of nonimmunized dogs and few studies about the
      identification of the viruses associated with diarrhea. To address this
      situation, stool samples from 325 dogs were analyzed by polymerase chain reaction
      for the detection of common enteric viruses such as Canine adenovirus (CAdV),
      Canine coronavirus (CCoV), Canine distemper virus (CDV), Canine rotavirus (CRV)
      and Carnivorous protoparvovirus 1 (canine parvovirus 2; CPV-2). At least one of
      these species was detected in 56.6% (184/325) of the samples. The viruses
      detected most frequently in either diarrheic or nondiarrheic dog feces were CPV-2
      (54.3% of the positive samples), CDV (45.1%) and CCoV (30.4%), followed by CRV
      (8.2%) and CAdV (4.9%). Only one agent was detected in the majority of the
      positive samples (63%), but co-infections were present in 37% of the positive
      samples and mainly included CDV and CPV-2. The data presented herein can improve
      the clinical knowledge in regions with low vaccine coverage and highlight the
      need to improve the methods used to control these infectious diseases in domestic
      dogs.

PMID- 29588199
TI  - Is a dose of 17D vaccine in the current context of Yellow Fever enough?

PMID- 29588200
TI  - Flow limitation and dysanapsis in children and adolescents with exertional
      dyspnea.
AB  - The consequence of dysanapsis, quantitated by dysanapsis ratio (DR), on
      expiratory flow limitation (EFL) during exercise in pediatric subjects was
      examined. EFL occurred in 80 (56%) subjects from an enriched sample of children
      and adolescents tested during investigation of exertional dyspnea. DR was lower
      in subjects with vs without EFL during exercise: (0.055 +/- 0.015 vs 0.067 +/-
      0.017, p < 0.001), and lower ratio correlated with greater extent of EFL (r = 
      0.64, p < 0.001). EFL was seen more often in boys: 67% vs 46% (p = 0.01), as
      girls had higher DR (0.063 +/- 0.016 vs 0.056 +/- 0.018, p = 0.007). Lower FEV1
      (95 +/- 17 vs 102 +/- 15%predicted, p < 0.005) and FEF50 (3.47 +/- 1.28 vs 4.08
      +/- 1.20 L s-1, p = 0.002) distinguished those with vs without EFL. Inspiratory
      capacity rose (IC) steadily, as work increased among those with EFL, whereas it
      fell to back resting levels after an initial rise in subjects without EFL. Low DR
      predicts EFL in pediatric subjects. Adjusting operating lung volume during
      exercise can mitigate EFL but this strategy may contribute to exertional dyspnea.

PMID- 29588201
TI  - Promotive effect of Bofutsushosan (Fangfengtongshengsan) on lipid and cholesterol
      excretion in feces in mice treated with a high-fat diet.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bofutsushosan (fangfengtongshengsan in Chinese,
      BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine
      comprising 18 crude drugs that is used for treating obesity and metabolic
      syndrome. AIM OF THE STUDY: We evaluated the promotive effects of BTS on lipid
      and cholesterol elimination in mice. MATERIALS AND METHODS: Mice were reared with
      a high-fat diet containing boiled water extract of BTS for 30 days, and their
      biochemical parameters as well as the weight and lipid content of feces were
      measured. We also measured cholesterol uptake into Caco-2 cells cultured with or
      without BTS extract. RESULTS: The body weight and amounts of visceral fat and
      subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric
      fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on
      day 30 were significantly lower in the BTS extract-treated groups than in the
      control in a dose-dependent manner. The amounts of lipid and cholesterol in the
      feces collected from day 6-23 were significantly greater than in the control.
      When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into
      cells was significantly reduced in a concentration-dependent manner. Among the
      components of BTS, the methanol extracts of Platycodi Radix and Zingiberis
      Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract
      the suppressive effect of BTS on cholesterol uptake into Caco-2 cells.
      CONCLUSIONS: BTS has beneficial effects on obesity and metabolic syndrome, and
      its mechanisms of action include the promotion of lipid elimination and the
      inhibition of cholesterol absorption in the intestine.

PMID- 29588202
TI  - Innovative edible packaging from mango kernel starch for the shelf life extension
      of red chili powder.
AB  - In this study mango kernel starch (MKS) based heat sealable pouches were
      developed for packing of red chili powder. The films were prepared by casting
      technique using glycerol, sorbitol and 1:1 mixture of glycerol and sorbitol and
      were sealed. All films showed better heat sealing capacity but glycerol films
      plasticized exhibited higher seal strength than their counterparts. The red chili
      powder was packed in the MKS film pouches while commercially available
      polyethylene (PE) film was used as control. The pungency and color of red chili
      powder was monitored during six months storage at 40 degrees C. The capsaicinoid
      content was extracted from the red chili with acetonitrile and evaluated
      quantitatively using spectrophotometric method. The extractable color was
      measured by ASTA method using acetone. The results showed significant differences
      in color and pungency of chili packed in MKS and PE pouches. The highest
      reduction in capsaicinoid content (pungency) of chili powder was observed in PE
      pouch (25.9%) while lowest was observed in MKS pouch containing sorbitol (15.7%).
      Similarly color loss was also highest in chili packed in PE pouch while lowest in
      MKS-sorbitol pouch.

PMID- 29588203
TI  - Synthesis of varisized chitosan-selenium nanocomposites through heating treatment
      and evaluation of their antioxidant properties.
AB  - Varisized chitosan-selenium (CS-Se) nanocomposites were synthesized through an
      innovative method. It is the first time to use CS both as reductant and
      stabilizer to synthesize selenium nanoparticles (SeNPs). By manipulating the
      temperature, the well-dispersed CS-Se nanocomposites were synthesized via a
      simple one pot reaction with the size ranging from 83 to 208nm before being
      characterized by TEM, DLS, UV-vis, FTIR, XRD and TG analyses. The results showed
      that SeO32- was reduced to a stable SeNPs colloid at a comparatively high
      temperature, the amino group and hydroxyl group of CS were conjugated to the
      surface of SeNPs. Besides, the antioxidant activities of CS-Se nanocomposites
      were investigated by DPPH, ABTS+, hydroxyl radical, metal ion chelating and
      reducing power assays, which proved to be concentration-dependent, size-dependent
      and exhibited good antioxidant activities. The results suggested that CS-Se
      nanocomposites might be considered as a more appropriate selenium-adding form to
      achieve antioxidative goals in food.

PMID- 29588204
TI  - Effect of cross-linking and oxidization on structure and properties of sesbania
      gum.
AB  - The effect of cross-linking and oxidization on the structure and properties of
      sesbania gum (SG) was studied using phosphorus oxychloride as a cross-linking
      agent, hydrogen peroxide as an oxidant, and ethanol as a solvent. The results
      showed that the oxidation of SG by hydrogen peroxide was essentially the breaking
      of long chains without hydroxyl groups being oxidized into carboxyl groups. The
      breakage of long chains was a key reason of reduction in viscosity. The
      disruption of SG granules caused by cross-linking was obviously different from
      the oxidization. The cross-linking had high selectivity, but the oxidization of
      hydrogen peroxide was random. The crystallinity degree of SG was reduced by cross
      linking and oxidization. The cross-linking and oxidization obviously changed the
      thermal properties of SG, and had obvious influence on the freeze-thaw stability,
      swelling power and retrogadation of SG. The cross-linking degree was well
      characterized by the surface hydroxyl numbers. The cross-linking was carried out
      only on SG granule surface according to evidence of alteration in surface
      hydroxyl numbers.

PMID- 29588205
TI  - Rational design of novel water-soluble ampholytic cellulose derivatives.
AB  - The development of new biocompatible, biodegradable functionalized biopolymers
      that can serve as scaffold for tissue regeneration or work as carriers for
      different bioactive molecules such as drugs, proteins, and enzymes remains a
      continuous challenge that need to be extensively explored. For this purpose,
      three water-soluble cellulose derivatives; namely 4(celluloseamino) butyric acid
      (CABA) 2(celluloseamino) succinic acid (CASA), and 3(celluloseamino) propane
      sulfonic acids (CAPSA) were synthesized from microcrystalline cellulose (MCC) via
      esterification with tosyl chloride that was followed by nucleophilic substitution
      by the proper aminoalkyl acid derivative. The products were characterized by
      elemental analyses, FTIR, 13C NMR spectroscopy. The thermal stability, surface
      morphology, and the elemental composition of the new ampholytic biopolymers were
      also studied by TGA, EDX-SEM. The new ampholytic cellulose derivatives were
      evaluated for their in vitro cytotoxicity on normal human retina cell line (RPE1)
      by MTT assay.

PMID- 29588206
TI  - Bio-active nanocomposite films based on nanocrystalline cellulose reinforced
      styrylquinoxalin-grafted-chitosan: Antibacterial and mechanical properties.
AB  - In this study, active nanocomposite films based on cellulose nanocrystalline
      (NCC) reinforced styrylquinoxalin-grafted-chitosan are prepared by solvent
      casting process. The structures of the two styrylquinoxaline derivatives were
      confirmed by FT-IR, 1H, 13C NMR spectral data and the study of the antibacterial
      activity against Escherichia coli (EC), Staphylococcus aureus (SA), Bacillus
      subtilis (BS) and Pseudomonas Aeruginosa (PA) exhibits that they have a good
      antibacterial activity against (PA). On their side, the styrylquinoxalin-g
      chitosan films are able to inhibit the growth of (PA) through their contact area
      without being damaged by the antibacterial test conditions. The addition of 5wt%
      of NCCs as nano-reinforcements revealed no change at the level of antibacterial
      activity but led to an important improvement of the mechanical properties (more
      than 60% and 90% improvement in Young's modulus and tensile strength,
      respectively) of the modified-chitosan films. Thereby, the present nanocomposite
      films are prepared by a simple way and featured by good mechanical and
      antibacterial properties which enhance the possibility to use them as bio-based
      products for biomedical and food packaging.

PMID- 29588207
TI  - Study on the effect of graphene and glycerol plasticizer on the properties of
      chitosan-graphene nanocomposites via in situ green chemical reduction of graphene
      oxide.
AB  - Unplasticized and glycerol plasticized chitosan/graphene (CS/GS) nanocomposites
      were synthesized via in situ chemical reduction of graphene oxide sheets (GO)
      with l-ascorbic acid (L-AA) as reductant by solution casting. The reduction of GO
      with L-AA was investigated to establish the optimal amount of reductant required
      to produce chemically reduced graphene sheets (GS). The combine effect of both
      nanofiller and glycerol on the structure, thermal, mechanical, and electrical
      properties of CS/GS nanocomposite films was evaluated. Materials were
      characterized by FT-IR, NMR, UV-Vis, XPS, XRD, Raman, SEM, TEM, and TGA. The
      results showed that GS sheets were homogeneously dispersed throughout the CS
      matrix, and that interactions between CS and the surface of GS took place. When
      compared with neat CS, nanocomposites showed a decrease in the crystallinity,
      better thermal stability under oxidative atmosphere, and improved mechanical
      properties, while maintained the thermal properties of CS under inert conditions.
      Combined use of glycerol and GS led to substantially enhanced mechanical
      properties. The electrical conductivity was increased with increasing GS loading
      in nanocomposite. This study demonstrates how CS/GS nanocomposites performance
      properties can be tailored by controlling GsS and plasticizer content.

PMID- 29588209
TI  - Infection of the chalcid parasitoid Pteromalus venustus Walker (Hymenoptera:
      Pteromalidae) with the male-killing symbiont Arsenophonus nasoniae (Gamma
      Proteobacteria: Enterobacteriaceae).
AB  - The male-killing symbiont Arsenophonus nasoniae is a gamma-proteobacterium that
      infects parasitic wasps; the male progeny of infected females exhibit increased
      embryonic death. In this study, we examined methods to horizontally infect
      Pteromalus venustus (a parasitoid infesting populations of the alfalfa
      leafcutting bee Megachile rotundata) with A. nasoniae. We then tested the success
      of these methods via semi-quantitative PCR and quantitative digital PCR, using a
      molecular marker specific to A. nasoniae. Controlled parasitoid mating
      experiments were then undertaken to determine whether infections of A. nasoniae
      in P. venustus induce the male-killing phenotype as has been reported for other
      host species; evidence of this male-killing phenotype was observed in the current
      study. Over the course of the eight parasitoid generations following introduction
      of A. nasoniae infection in P. venustus, the male component of the parasitoid sex
      ratio was substantially reduced in the infected population (1.05 ?: 1.00 ?)
      compared to the control population (2.46 ?: 1.00 ?). Establishment of stable A.
      nasoniae infections in P. venustus populations could lower the proportion of male
      progeny, thus negatively impacting the mating success of females, and reducing
      overall populations of the parasitoid in alfalfa leafcutting bee populations.

PMID- 29588208
TI  - Application of HTLV-1 tax transgenic mice for therapeutic intervention.
AB  - Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by
      infection of human T-cell leukemia virus type I (HTLV-I). Although the
      pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important
      role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy
      resistance of ATL leads the poor prognosis of this disease. In order to
      understand the pathogenesis and establish an animal model useful for therapy
      attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal
      promoter to restrict the Tax expression in T-cells. The HTLV-1 Tax transgenic
      mice developed diffuse large-cell lymphomas and leukemia with the similar
      features of a clinical, pathological and immunological characteristic of acute
      ATL. The fulminant disease also developed rapidly in SCID mice after engraftment
      of mouse ATL cells derived from the transgenic mice. In this review, we introduce
      the therapeutic attempts using this animal model and discuss the possible
      signaling pathway for a therapeutic target.

PMID- 29588210
TI  - Relating the tableting behavior of piroxicam polytypes to their crystal
      structures using energy-vector models.
AB  - Piroxicam crystallises into two polytypes, alpha1 and alpha2, with crystal
      structures that contain identical molecular layers but differ in the way that
      these layers are stacked. In spite of having close structural similarity, the
      polytypes have significantly different powder tabletting behaviour: alpha2 forms
      only weak tablets at low pressures accompanied by extensive capping and
      lamination, which make it impossible to form intact tablets above 100 MPa, while
      alpha1 exhibits superior tabletability over the investigated pressure range (up
      to 140 MPa). The potential structural origin of the different behaviour is sought
      using energy-vector models, produced from pairwise intermolecular interaction
      energies calculated using the PIXEL method. The analysis reveals that the most
      stabilising intermolecular interactions define columns in both crystal
      structures. In alpha2, a strongly stabilising interaction between inversion
      related molecules links these columns into a 2-D network, while no comparable
      interaction exists in alpha1. The higher dimensionality of the energy-vector
      model in alpha2 may be one contributor to its inferior tabletability. A
      consideration of probable slip planes in the structures identifies regions where
      the benzothiazine groups of the molecules meet. The energy-vector models in this
      region are geometrically similar for both structures, but the interactions are
      more stabilising in alpha2 compared to alpha1. This feature may also contribute
      to the inferior tabletability of alpha2.

PMID- 29588211
TI  - Escherichia coli O157:H7 virulence factors differentially impact cattle and bison
      macrophage killing capacity.
AB  - Enterohemorrhagic Escherichia coli O157:H7 colonizes the gastrointestinal tract
      of ruminants, including cattle and bison, which are reservoirs of these zoonotic
      disease-causing bacteria. Healthy animals colonized by E. coli O157:H7 do not
      experience clinical symptoms of the disease induced by E. coli O157:H7 infections
      in humans; however, a variety of host immunological factors may play a role in
      the amount and frequency of fecal shedding of E. coli O157:H7 by ruminant
      reservoirs. How gastrointestinal colonization by E. coli O157:H7 impacts these
      host animal immunological factors is unknown. Here, various isogenic mutant
      strains of a foodborne isolate of E. coli O157:H7 were used to evaluate bacterial
      killing capacity of macrophages of cattle and bison, the two ruminant species.
      Cattle macrophages demonstrated an enhanced ability to phagocytose and kill E.
      coli O157:H7 compared to bison macrophages, and killing ability was impacted by
      E. coli O157:H7 virulence gene expression. These findings suggest that the
      macrophage responses to E. coli O157:H7 might play a role in the variations
      observed in E. coli O157:H7 fecal shedding by ruminants in nature.

PMID- 29588212
TI  - Modulatory role of conspecific alarm substance on aggression and brain monoamine
      oxidase activity in two zebrafish populations.

PMID- 29588213
TI  - Synthesis and evaluation of the antibacterial activities of aryl substituted
      dihydrotriazine derivatives.
AB  - Five series of dihydrotriazine derivatives containing chalcone (13a-i), phenoxy
      acetophenone (14a-b), benzyl benzene (15a-c), naphthoxyl acetophenone (16a-b) and
      benzyl naphthalene (17a-h) moieties were designed and synthesized. The
      antibacterial and antifungal activities of these compounds were evaluated against
      several strains of Gram-positive and Gram-negative bacteria, as well as a single
      fungus. Compound 17h was found to be the most potent of all of the compounds
      tested, with an MIC value of 0.5 MUg/mL against several Gram-positive
      (Staphylococcus aureus 4220 and QRSA CCARM 3505) and Gram-negative (Escherichia
      coli 1924) strains of bacteria. However, this compound was inactive against
      Pseudomonas aeruginosa 2742 and Salmonella typhimurium 2421, indicating that its
      antibacterial spectrum is similar to those of the positive controls gatifloxacin
      and moxifloxacin. The cytotoxic activity of the compound 13i, 16b and 17h was
      assessed in Human normal liver cells.

PMID- 29588214
TI  - Synthesis of (aminoalkyl)cycleanine analogues: cytotoxicity, cellular uptake, and
      apoptosis induction in ovarian cancer cells.
AB  - Our previous studies demonstrated that cycleanine, a macrocyclic
      bisbenzylisoquinoline (BBIQ) alkaloid, showed potent anti-ovarian cancer activity
      via apoptosis induction. Here, we synthesized two novel (aminoalkyl)cycleanine
      analogues (2 and 3) through a simple and efficient two-step reaction starting
      from cycleanine isolated from Triclisia subcordata Oliv. These analogues showed
      greater potency than the unmodified cycleanine in three human ovarian cancer cell
      lines. Both 2 and 3 induced apoptosis in ovarian cancer cells by activations of
      caspases 3/7, cleavage of PARP, increase in subG1 cell cycle phase and in the
      percentage of apoptotic cells. Further confocal fluorescence microscopy analysis
      confirmed the cellular uptake of alkaloids in ovarian cancer cells by using the
      unique (alkynyl)cycleanine (3) via click chemistry reaction. Our results suggest
      that cycleanine could be a hit compound for the future development in attacking
      ovarian cancer.

PMID- 29588215
TI  - Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective
      and orally bioavailable LRRK2 inhibitors.
AB  - Inhibition of LRRK2 kinase activity with small molecules has emerged as a
      potential novel therapeutic treatment for Parkinson's disease. Herein we disclose
      the discovery of a 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine series as potent
      LRRK2 inhibitors identified through a kinase-focused set screening. Optimization
      of the physicochemical properties and kinase selectivity led to the discovery of
      compound 7, which exhibited potent in vitro inhibition of LRRK2 kinase activity,
      good physicochemical properties and kinase selectivity across the kinome.
      Moreover, compound 7 was able to penetrate into the CNS, and in vivo pharmacology
      studies revealed significant inhibition of Ser935 phosphorylation in the brain of
      both rats (30 and 100 mg/kg) and mice (45 mg/kg) following oral administration.

PMID- 29588216
TI  - Bladder Management and Continence Outcomes in Adults with Spina Bifida: Results
      from the National Spina Bifida Patient Registry, 2009 to 2015.
AB  - PURPOSE: Most children with spina bifida now survive into adulthood, although
      most have neuropathic bladder with potential complications of incontinence,
      infection, renal damage and diminished quality of life. In this study we sought
      to 1) describe contemporary bladder management and continence outcomes of adults
      with spina bifida, 2) describe differences from younger individuals and 3) assess
      for association with socioeconomic factors. MATERIALS AND METHODS: We analyzed
      data on bladder management and outcomes in adults with spina bifida from the
      National Spina Bifida Patient Registry. A strict definition of continence was
      used. Results were compared to young children (age 5 to 11 years) and adolescents
      (12 to 19). Statistical analysis compared cohorts by gender, ethnicity, spina
      bifida type, lesion level, insurance status, educational attainment, employment
      status and continence. RESULTS: A total of 5,250 patients with spina bifida were
      included, of whom 1,372 (26.1%) were adults. Of the adult patients 45.8% did not
      take medication, but 76.8% performed clean intermittent catheterization.
      Continence was decreased in adults with myelomeningocele (45.8%) vs those with
      nonmyelomeningocele spina bifida (63.1%, p <0.0001). Continence rates were higher
      in the older cohorts with myelomeningocele (p <0.0001) but not in those with
      nonmyelomeningocele spina bifida (p = 0.1192). Bladder management and history of
      urological surgery varied among age groups. On univariate analysis with spina
      bifida related or socioeconomic variables continence was significantly associated
      with educational level but on multivariable logistic regression analysis bladder
      continence was significantly associated with employment status only. CONCLUSIONS:
      Bladder management techniques differ between adults and children with spina
      bifida. Bladder continence outcomes were better in adults, with nearly half
      reporting continence. Continence was significantly associated with employment
      status in patients age 25 years or older.

PMID- 29588217
TI  - A review of nanoparticle photosensitizer drug delivery uptake systems for
      photodynamic treatment of lung cancer.
AB  - Lung cancer is a leading cause of cancer related deaths worldwide and so current
      research is focused on trying to improve treatment modalities, such as
      photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a
      photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a
      patient, it can either passively or actively accumulate within a tumour site and
      once exposed to a specific wavelength of light, it is stimulated to produce
      reactive oxygen species (ROS), resulting in tumour destruction. However, the
      efficacy of ROS generation for tumour destruction is highly dependent on the
      accumulation of the PS in tumour cells. Thus PS selective/targeted uptake and
      delivery in tumour cells is a crucial factor in PDT cancer drug absorption
      studies. Generally, within non-targeted drug delivery mechanisms, only small
      amounts of PS is able to passively accumulates in tumour sites due to the
      enhanced permeability and retention (EPR) effect and the remainder distributes
      into healthy tissues, causing side effects. Thus to improve the efficacy of PDT,
      research is currently focused on the development of specific receptor based
      photosynthetic nanocarrier drugs, which promotes the active uptake and absorption
      of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this
      review is to focus on current non-targeted passive versus specifically active
      targeted PS nanoparticle drug delivery systems, that have been investigated for
      the PDT treatment of lung cancer and so to deduce its efficacy and recent
      advancements.

PMID- 29588218
TI  - Alloreactivity and allorecognition of syngeneic and allogeneic mitochondria.
AB  - Previously, we have demonstrated that the transplantation of autologous
      mitochondria is cardioprotective. No immune or autoimmune response was detectable
      following the single injection of autologous mitochondria. To expand the
      therapeutic potential and safety of mitochondrial transplantation, we now
      investigate the immune response to single and serial injections of syngeneic and
      allogeneic mitochondria delivered by intraperitoneal injection. Our results
      demonstrate that there is no direct or indirect, acute or chronic alloreactivity,
      allorecognition or damage-associated molecular pattern molecules (DAMPs) reaction
      to single or serial injections of either syngeneic or allogeneic mitochondria.

PMID- 29588219
TI  - Exercise-induced reductions in mitochondrial ADP sensitivity contribute to the
      induction of gene expression and mitochondrial biogenesis through enhanced
      mitochondrial H2O2 emission.
AB  - Acute exercise rapidly induces mitochondrial gene expression, however, the
      intracellular events regulating this process remain incompletely understood. The
      purpose of this study was to determine whether reductions in mitochondrial ADP
      sensitivity during exercise have a biological role in regulating mitochondrial
      derived reactive oxygen species (ROS) production and the induction of
      mitochondrial biogenesis. Mitochondrial creatine kinase wildtype (WT) and
      knockout (KO) mice have divergent responses in ADP sensitivity during exercise,
      and we therefore used these mice to determine the relationship between
      mitochondrial ADP sensitivity, ROS production, and mitochondrial adaptations to
      exercise. In WT mice, acute exercise reduced mitochondrial ADP respiratory
      sensitivity and the ability of ADP to suppress ROS production, while increasing
      mitochondrial gene transcription (PGC-1alpha, PGC-1beta and PDK4). In stark
      contrast, in KO mice, exercise increased ADP sensitivity, reduced mitochondrial
      ROS emission, and did not induce gene transcription. Despite the divergence in
      mRNA responses, exercise similarly induced calcium/calmodulin-dependent protein
      kinase II (CaMKII) and AMP-activated protein kinase (AMPK) phosphorylation in WT
      and KO mice, however only WT mice were associated with redox stress (4HNE). These
      data implicate acute changes in ADP sensitivity in mitochondrial adaptations to
      exercise. To further examine this we chronically exercise trained mice. While
      training increased mitochondrial content and reduced ADP sensitivity in WT mice,
      KO mice did not exhibit adaptations to exercise. Combined, these data suggest
      that exercise-induced attenuations in mitochondrial ADP sensitivity mediate redox
      signals that contribute to the induction of acute and chronic mitochondrial
      adaptations.

PMID- 29588220
TI  - A novel regulatory function of CDKN1A/p21 in TNFalpha-induced matrix
      metalloproteinase 9-dependent migration and invasion of triple-negative breast
      cancer cells.
AB  - Metastasis is the leading cause of mortality in patients with highly invasive
      cancers and, as such, is a major problem for medicine. It has been increasingly
      recognized that cancer-related inflammation plays an important role in promoting
      invasion and the metastatic process in which cell motility and upregulation of
      proteolytic enzymes are crucial events. TNFalpha is a proinflammatory cytokine
      known to stimulate synthesis of MMP9, a zinc- and calcium-dependent endopeptidase
      contributing to the regulation of ECM remodeling and cell signaling. However, the
      precise molecular mechanism of TNFalpha-induced MMP9 gene expression in cancers
      is still not fully understood. This study shows that TNFalpha-induced cell
      migration and invasion involve ERK1/2-dependent up-regulation of CDKN1A/p21
      expression in highly aggressive breast cancer cells and that CDKN1A/p21 plays an
      important regulatory role in TNFalpha-induced MMP9 gene expression, indicating an
      unknown function of CDKN1A/p21 as a regulator of proteolytic activity in cancer
      cells.

PMID- 29588221
TI  - A brief period of sleep deprivation causes spine loss in the dentate gyrus of
      mice.
AB  - Sleep and sleep loss have a profound impact on hippocampal function, leading to
      memory impairments. Modifications in the strength of synaptic connections
      directly influences neuronal communication, which is vital for normal brain
      function, as well as the processing and storage of information. In a recently
      published study, we found that as little as five hours of sleep deprivation
      impaired hippocampus-dependent memory consolidation, which was accompanied by a
      reduction in dendritic spine numbers in hippocampal area CA1. Surprisingly, loss
      of sleep did not alter the spine density of CA3 neurons. Although sleep
      deprivation has been reported to affect the function of the dentate gyrus, it is
      unclear whether a brief period of sleep deprivation impacts spine density in this
      region. Here, we investigated the impact of a brief period of sleep deprivation
      on dendritic structure in the dentate gyrus of the dorsal hippocampus. We found
      that five hours of sleep loss reduces spine density in the dentate gyrus with a
      prominent effect on branched spines. Interestingly, the inferior blade of the
      dentate gyrus seems to be more vulnerable in terms of spine loss than the
      superior blade. This decrease in spine density predominantly in the inferior
      blade of the dentate gyrus may contribute to the memory deficits observed after
      sleep loss, as structural reorganization of synaptic networks in this subregion
      is fundamental for cognitive processes.

PMID- 29588222
TI  - The transformation of multi-sensory experiences into memories during sleep.
AB  - Our everyday lives present us with a continuous stream of multi-modal sensory
      inputs. While most of this information is soon forgotten, sensory information
      associated with salient experiences can leave long-lasting memories in our minds.
      Extensive human and animal research has established that the hippocampus is
      critically involved in this process of memory formation and consolidation.
      However, the underlying mechanistic details are still only partially understood.
      Specifically, the hippocampus has often been suggested to encode information
      during experience, temporarily store it, and gradually transfer this information
      to the cortex during sleep. In rodents, ample evidence has supported this notion
      in the context of spatial memory, yet whether this process adequately describes
      the consolidation of multi-sensory experiences into memories is unclear. Here,
      focusing on rodent studies, I examine how multi-sensory experiences are
      consolidated into long term memories by hippocampal and cortical circuits during
      sleep. I propose that in contrast to the classical model of memory consolidation,
      the cortex is a "fast learner" that has a rapid and instructive role in shaping
      hippocampal-dependent memory consolidation. The proposed model may offer
      mechanistic insight into memory biasing using sensory cues during sleep.

PMID- 29588224
TI  - Dissociations of conscious and unconscious perception in TMS-induced blindsight.
AB  - As with some patients with primary visual cortex (V1) damage, transcranial
      magnetic stimulation (TMS) over V1 reliably induces blindsight, whereby observers
      can correctly discriminate the attributes of visual stimuli despite being unable
      to detect them. This TMS-induced blindsight has been demonstrated to reflect a
      form of unconscious vision that relies upon different neural pathways than with
      conscious vision. However, the timing of the neural processes mediating TMS
      induced blindsight has been unclear, especially when considering suggestions that
      TMS interferes with feedback processes to V1 that mediate conscious visual
      perception. To better elucidate the neural mechanisms that give rise to
      blindsight, we tested TMS-induced blindsight for the orientation of visual
      stimuli across a range of stimulus onset asynchronies (SOAs) to assess how
      different latencies of visual cortex disruption, relative to a visual stimulus,
      affect detection rates and forced-choice discrimination accuracy. At all TMS
      latencies, including at SOAs with substantial visual suppression from TMS,
      discrimination performance was significantly above-chance, demonstrating the
      consistency of TMS-induced blindsight. Crucially, we observed two windows of
      maximum visual suppression from TMS at SOAs between 65 and 105 ms, but consistent
      above-chance discrimination performance accuracy across these windows. However,
      at longer SOAs, detection and discrimination covaried, suggesting a dependency of
      discrimination performance on detection only when detection rates exceed
      threshold levels of normal vision. Taken together, these results indicate that
      unconscious discrimination occurs independently of detection, including at TMS
      intervals that optimally interfere with conscious visual perception. They further
      suggest that forced-choice discrimination is less dependent on feedback processes
      to V1 than visual awareness and that TMS-induced blindsight is not the same as
      near-threshold vision.

PMID- 29588223
TI  - Translation, adaptation and psychometric validation of the Good Perioperative
      Nursing Care Scale (GPNCS) with surgical patients in perioperative care.
AB  - AIM: To test the psychometric validity of the Good Perioperative Nursing Care
      Scale (GPNCS), a self-administered questionnaire, following translation and
      adaptation. INTRODUCTION: Patients' satisfaction with and experience of nursing
      care in orthopaedic or perioperative settings are currently not routinely
      measured and few standardized patient-reported experience measurement tools exist
      for these settings. MATERIALS AND METHODS: Cross-sectional survey. The 34
      question, seven-factor questionnaire was translated, adapted, and face-validated;
      the translated version was then validated with a group of surgical patients in
      perioperative settings. The internal consistency of the translated version was
      validated and tested using confirmatory factor analysis combined with Cronbach's
      alpha. RESULTS: In the orthopaedic department of a regional public hospital, 361
      acute, traumatic and elective surgical patients were screened for eligibility;
      215 were included. The full-scale model fit estimates were moderate. Factor
      loadings typically ranged from 0.65 to 0.97, except for the questions concerning
      Technical Skills (0.38-0.63) and Nursing Process (0.28). The Cronbach's alpha
      value for the total scale score was 0.92, with subfactors ranging from 0.72 to
      0.87. CONCLUSION: Providing evidence for quality, or lack thereof, the Danish
      version of the GPNCS is a valid tool for measuring surgical patients' experiences
      with perioperative nursing care. The electronic version proved practical.
      RELEVANCE TO CLINICAL PRACTICE: The validated Danish version of the tool will
      help healthcare professionals to identify areas of nursing care that need
      improvement, facilitate international benchmarking of units and enable comparison
      of care quality, nationally and internationally.

PMID- 29588225
TI  - Identification of task sets within and across stimulus modalities.
AB  - Previous studies have shown that task sets can be identified from functional
      magnetic resonance imaging (fMRI) data. However, these results may be partially
      confounded by differences in stimulus features associated with the different
      tasks. We disentangle stimulus modality and task features by presenting the same
      stimulus while varying task, and conversely, presenting different stimuli using
      the same task. Analyses were conducted on fMRI data previously collected on
      twenty participants who made either affective or semantic judgements of the same
      music pieces or the same silent video clips (Kim et al., 2017). Holding stimuli
      constant, task set was identified from fMRI data across individuals from both
      task activation data and functional connectivity data. Thus, we were able to
      identify whether participants made affective or semantic judgments when exposed
      to identical stimuli based on the task activation and functional connectivity
      data from other participants. Moreover, task set was successfully identified for
      cross-modal prediction in which stimuli in the training set bore no resemblance
      to those in the test set (e.g., using videos data to predict task for music
      data). Brain regions that were sensitive to tasks irrespective of sensory
      modality were identified by univariate and searchlight analyses of fMRI data.
      Consistent with a frontal-parietal network, middle frontal gyrus, inferior
      parietal gyrus, mid-cingulate cortex, and superior temporal sulcus were found to
      be key regions distinguishing the two task sets.

PMID- 29588226
TI  - The current status of the magnocellular theory of developmental dyslexia.
AB  - Some people doubt that the concept of developmental dyslexia (DD) is useful at
      all because the phonological weaknesses seen in DD cannot be distinguished from
      those found in every person with poor reading skills, whatever their cause. Here
      I argue that true DD is characterised by poor temporal processing, hence impaired
      visual and auditory sequencing, that is caused by impaired development of
      transient/magnocellular (M-) systems throughout the brain. These deficits can be
      measured in order to distinguish the causes of the phonological weaknesses in DD
      from those causing similar deficits in other types of poor reading. Importantly
      this knowledge can be exploited to develop effective improvements in treatment.
      The evidence for impaired visual magnocellular function in many, if not all,
      people with dyslexia is now overwhelming; it is supported not only by
      psychophysical tests of M- function, but also by electrophysiological, eye
      movement, attentional, imaging, interventional and genetic findings. Analogously,
      auditory temporal processing is mediated by auditory transient, 'magnocellular',
      processing systems, and evidence is accumulating persuasively that this system is
      also impaired in dyslexics. I briefly introduce the idea that 'motor
      magnocellular systems' may also be impaired in dyslexia, then consider genetic,
      immunological and nutritional factors that interact to cause the impaired
      magnocellular phenotype. I then discuss why the dyslexic phenotype is so common
      by speculating about what strengths it might confer that would maintain the
      responsible genes in the human genome.

PMID- 29588227
TI  - Resting-state functional connectivity predicts the ability to adapt arm reaching
      in a robot-mediated force field.
AB  - Motor deficits are common outcomes of neurological conditions such as stroke. In
      order to design personalised motor rehabilitation programmes such as robot
      assisted therapy, it would be advantageous to predict how a patient might respond
      to such treatment. Spontaneous neural activity has been observed to predict
      differences in the ability to learn a new motor behaviour in both healthy and
      stroke populations. This study investigated whether spontaneous resting-state
      functional connectivity could predict the degree of motor adaptation of right
      (dominant) upper limb reaching in response to a robot-mediated force field.
      Spontaneous neural activity was measured using resting-state
      electroencephalography (EEG) in healthy adults before a single session of motor
      adaptation. The degree of beta frequency (beta; 15-25 Hz) resting-state
      functional connectivity between contralateral electrodes overlying the left
      primary motor cortex (M1) and the anterior prefrontal cortex (aPFC) could predict
      the subsequent degree of motor adaptation. This result provides novel evidence
      for the functional significance of resting-state synchronization dynamics in
      predicting the degree of motor adaptation in a healthy sample. This study
      constitutes a promising first step towards the identification of patients who
      will likely gain most from using robot-mediated upper limb rehabilitation
      training based on simple measures of spontaneous neural activity.

PMID- 29588228
TI  - Neural oscillations during conditional associative learning.
AB  - Associative learning requires mapping between complex stimuli and behavioural
      responses. When multiple stimuli are involved, conditional associative learning
      is a gradual process with learning based on trial and error. It is established
      that a distributed network of regions track associative learning, however the
      role of neural oscillations in human learning remains less clear. Here we used
      scalp EEG to test how neural oscillations change during learning of arbitrary
      visuo-motor associations. Participants learned to associative 48 different
      abstract shapes to one of four button responses through trial and error over
      repetitions of the shapes. To quantify how well the associations were learned for
      each trial, we used a state-space computational model of learning that provided a
      probability of each trial being correct given past performance for that stimulus,
      that we take as a measure of the strength of the association. We used linear
      modelling to relate single-trial neural oscillations to single-trial measures of
      association strength. We found frontal midline theta oscillations during the
      delay period tracked learning, where theta activity was strongest during the
      early stages of learning and declined as the associations were formed. Further,
      posterior alpha and low-beta oscillations in the cue period showed strong
      desynchronised activity early in learning, while stronger alpha activity during
      the delay period was seen as associations became well learned. Moreover, the
      magnitude of these effects during early learning, before the associations were
      learned, related to improvements in memory seen on the next presentation of the
      stimulus. The current study provides clear evidence that frontal theta and
      posterior alpha/beta oscillations play a key role during associative memory
      formation.

PMID- 29588229
TI  - Microstructural imaging of human neocortex in vivo.
AB  - The neocortex of the human brain is the seat of higher brain function. Modern
      imaging techniques, chief among them magnetic resonance imaging (MRI), allow non
      invasive imaging of this important structure. Knowledge of the microstructure of
      the neocortex has classically come from post-mortem histological studies of human
      tissue, and extrapolations from invasive animal studies. From these studies, we
      know that the scale of important neocortical structure spans six orders of
      magnitude, ranging from the size of axonal diameters (microns), to the size of
      cortical areas responsible for integrating sensory information (centimetres). MRI
      presents an opportunity to move beyond classical methods, because MRI is non
      invasive and MRI contrast is sensitive to neocortical microstructure over all
      these length scales. MRI thus allows inferences to be made about neocortical
      microstructure in vivo, i.e. MRI-based in vivo histology. We review recent
      literature that has applied and developed MRI-based in vivo histology to probe
      the microstructure of the human neocortex, focusing specifically on myelin, iron,
      and neuronal fibre mapping. We find that applications such as cortical
      parcellation (using [Formula: see text] maps as proxies for myelin content) and
      investigation of cortical iron deposition with age (using [Formula: see text]
      maps) are already contributing to the frontiers of knowledge in neuroscience.
      Neuronal fibre mapping in the cortex remains challenging in vivo, but recent
      improvements in diffusion MRI hold promise for exciting applications in the near
      future. The literature also suggests that utilising multiple complementary
      quantitative MRI maps could increase the specificity of inferences about
      neocortical microstructure relative to contemporary techniques, but that further
      investment in modelling is required to appropriately combine the maps. In vivo
      histology of human neocortical microstructure is undergoing rapid development.
      Future developments will improve its specificity, sensitivity, and clinical
      applicability, granting an ever greater ability to investigate neuroscientific
      and clinical questions about the human neocortex.

PMID- 29588230
TI  - Associations between maternal cytokine levels during gestation and measures of
      child cognitive abilities and executive functioning.
AB  - Preclinical studies demonstrate that environmentally-induced alterations in
      inflammatory cytokines generated by the maternal and fetal immune system can
      significantly impact fetal brain development. Yet, the relationship between
      maternal cytokines during gestation and later cognitive ability and executive
      function remains understudied. Children (n = 246) were born of mothers enrolled
      in the Newborn Epigenetic Study - a prospective pre-birth cohort in the
      Southeastern US. We characterized seven cytokines [IL-1beta, IL-4,IL-6, IL-12p70,
      IL-17A, tumor necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma)]
      and one chemokine (IL-8) from maternal plasma collected during pregnancy. We
      assessed children's cognitive abilities and executive functioning at a mean age
      of 4.5 (SD = 1.1) years. Children's DAS-II and NIH toolbox scores were regressed
      on cytokines and the chemokine, controlling for maternal age, race, education,
      body mass index, IQ, parity, smoking status, delivery type, gestational weeks,
      and child birth weight and sex. Higher IL-12p70 (betaIL-12p70 = 4.26, p = 0.023)
      and IL-17A (betaIL-17A = 3.70, p = 0.042) levels were related to higher DAS-II
      GCA score, whereas higher IL-1beta (betaIL-1B = -6.07, p = 0.003) was related to
      lower GCA score. Higher IL-12p70 was related to higher performance on NIH toolbox
      measures of executive functions related to inhibitory control and attention
      (betaIL-12p70 = 5.20, p = 0.046) and cognitive flexibility (betaIL-12p70 = 5.10,
      p = 0.047). Results suggest that dysregulation in gestational immune activity are
      associated with child cognitive ability and executive functioning.

PMID- 29588231
TI  - Developmental psychoneuroimmunology grows up.

PMID- 29588232
TI  - The effect of beta-adrenergic blockade on inflammatory and cardiovascular
      responses to acute mental stress.
AB  - Acute mental stress elicits increases in plasma cytokine concentrations in
      humans, but the underlying mechanisms remain poorly understood. We assessed the
      impact of beta-adrenergic blockade on plasma interleukin 6 (IL-6) and IL-1
      receptor antagonist (IL-1Ra) responses in a parallel group, double-blind
      randomised placebo-controlled trial involving 64 healthy young adult volunteers.
      Participants were administered 80 mg slow-release propranolol or placebo daily
      for 7 days before the stress testing session in which responses to 3 behavioural
      challenges (public speaking, mirror tracing, mental arithmetic) were evaluated.
      Propranolol administration was associated with reduced baseline levels of heart
      rate and IL-1Ra, and systolic blood pressure (BP) in men. Tasks stimulated
      increased plasma IL-6 concentrations sampled 45 min and 75 min after challenge,
      but these responses were blocked by propranolol in men (p < 0.001). Propranolol
      did not influence IL-6 responses in women, or IL-1Ra in either sex. Blood
      pressure and heart rate increased markedly during the tasks, but there was no
      differential stress reactivity in propranolol and placebo conditions. The results
      of the study support a role of sympathetic nervous system activation in
      stimulating acute IL-6 responses to stress, but only in men. The reasons for the
      differences between men and women remain to be resolved.

PMID- 29588234
TI  - Metabolic engineering tools in model cyanobacteria.
AB  - Developing sustainable routes for producing chemicals and fuels is one of the
      most important challenges in metabolic engineering. Photoautotrophic hosts are
      particularly attractive because of their potential to utilize light as an energy
      source and CO2 as a carbon substrate through photosynthesis. Cyanobacteria are
      unicellular organisms capable of photosynthesis and CO2 fixation. While
      engineering in heterotrophs, such as Escherichia coli, has result in a plethora
      of tools for strain development and hosts capable of producing valuable chemicals
      efficiently, these techniques are not always directly transferable to
      cyanobacteria. However, recent efforts have led to an increase in the scope and
      scale of chemicals that cyanobacteria can produce. Adaptations of important
      metabolic engineering tools have also been optimized to function in
      photoautotrophic hosts, which include Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR)-Cas9, 13C Metabolic Flux Analysis (MFA), and Genome
      Scale Modeling (GSM). This review explores innovations in cyanobacterial
      metabolic engineering, and highlights how photoautotrophic metabolism has shaped
      their development.

PMID- 29588233
TI  - Postpartum increases in cerebral edema and inflammation in response to placental
      ischemia during pregnancy.
AB  - Reduced placental blood flow results in placental ischemia, an initiating event
      in the pathophysiology of preeclampsia, a hypertensive pregnancy disorder. While
      studies show increased mortality risk from Alzheimer's disease, stroke, and
      cerebrovascular complications in women with a history of preeclampsia, the
      underlying mechanisms are unknown. During pregnancy, placental ischemia, induced
      by reducing uterine perfusion pressure (RUPP), leads to cerebral edema and
      increased blood-brain barrier (BBB) permeability; however whether these
      complications persist after delivery is not known. Therefore, we tested the
      hypothesis that placental ischemia contributes to postpartum cerebral edema and
      neuroinflammation. On gestational day 14, time-pregnant Sprague Dawley rats
      underwent Sham (n = 10) or RUPP (n = 9) surgery and brain tissue collected 2
      months post-delivery. Water content increased in posterior cortex but not
      hippocampus, striatum, or anterior cerebrum following RUPP. Using a rat cytokine
      multi-plex kit, posterior cortical IL-17, IL-1alpha, IL-1beta, Leptin, and MIP2
      increased while hippocampal IL-4, IL-12(p70) and RANTES increased and IL-18
      decreased following RUPP. Western blot analysis showed no changes in astrocyte
      marker, Glial Fibrillary Acidic Protein (GFAP); however, the microglia marker,
      ionized calcium binding adaptor molecule (Iba1) tended to increase in hippocampus
      of RUPP-exposed rats. Immunofluorescence staining revealed reduced number of
      posterior cortical microglia but increased activated (Type 4) microglia in RUPP.
      Astrocyte number increased in both regions but area covered by astrocytes
      increased only in posterior cortex following RUPP. BBB-associated proteins,
      Claudin-1, Aquaporin-4, and zonular occludens-1 expression were unaltered;
      however, posterior cortical occludin decreased. These results suggest that 2
      months postpartum, neuroinflammation, along with decreased occludin expression,
      may partly explain posterior cortical edema in rats with history of placental
      ischemia.

PMID- 29588235
TI  - A Comparison of Computed Tomography-Based Scales with and without Consideration
      of the Presence or Absence of Intraventricular Hemorrhage in Patients with
      Aneurysmal Subarachnoid Hemorrhage.
AB  - OBJECTIVE: There has been controversy as to whether intraventricular hemorrhage
      (IVH) after aneurysmal subarachnoid hemorrhage (SAH) contributes to angiographic
      cerebral vasospasm (aCV) and delayed cerebral ischemia (DCI). Computed tomography
      based SAH scales that did and did not consider IVH were compared in terms of
      ability to predict aCV, DCI, and outcome. METHODS: We reviewed 390 patients with
      ruptured aneurysms who had been treated surgically by day 3 by the same surgeon
      (T.I.). aCV was graded as 0-4. Outcome at 6 months was classified using the
      Glasgow Outcome Scale. Inagawa SAH grades and scores, for which only SAH was
      evaluated, were compared with scales that evaluated both SAH and IVH (Fisher,
      Claassen, and Frontera grades, and Hijdra score). The area under the receiver
      operating characteristic curve was calculated to compare severe aCV (grade 3-4),
      DCI, or poor outcome (Glasgow Outcome Scale score 1-3). RESULTS: The Inagawa
      grade showed constant and significant intergrade differences in both aCV and DCI.
      The Inagawa grade area under the receiver operating characteristic curve values
      were highest among the scales examined. In the Fisher, Claassen, and Frontera
      grades, IVH was unlikely to be related to aCV and DCI. There was no significant
      difference in aCV grade or DCI occurrence between the Inagawa and Hijdra scores.
      In contrast, the presence of IVH was significantly associated with poor outcome.
      CONCLUSIONS: In patients with aneurysmal SAH, IVH is an important factor
      affecting patient outcome, whereas computed tomography-based SAH scales that do
      not consider IVH are superior to scales that do consider it for prediction of aCV
      or DCI.

PMID- 29588236
TI  - Predicting Successful Treatment of Intracranial Aneurysms with the Pipeline
      Embolization Device Through Meta-Regression.
AB  - OBJECTIVE: To conduct meta-regression for the identification of clinically
      meaningful characteristics that can predict successful treatment of intracranial
      aneurysms with the Pipeline Embolization Device (PED). METHODS: Using the key
      word "Pipeline Embolization Device" and prespecified eligibility criteria, we
      searched PubMed and EMBASE and identified 105 original research articles (10,813
      patients) published or in press (April 6, 2011, to December 31, 2016) focused on
      safety and/or effectiveness of PED. We constructed meta-regression models to
      identify predictors of 3 measures of PED treatment success, specifically rates of
      aneurysm occlusion, modified Rankin Scale score, and death. Rates were loge
      transformed, and the adjusted R2 statistic was reported for each model. RESULTS:
      Aneurysm morphology and type accounted for substantial variation in 1-year
      aneurysm occlusion rate (14 studies with 689 patients; Radj2 = 88.91%). By
      contrast, predictors of 6-months aneurysm occlusion rate (aneurysm location,
      aneurysm type; 24 studies with 1321 patients; Radj2 = 31.67%) and aneurysm
      occlusion rate at unspecified follow-up time (year of publication, mean duration
      of angiographic follow-up; 34 studies with 1663 patients, Radj2 = 42.82%)
      accounted for less variability. Few predictors were identified for death rate
      (number of patients, aneurysm morphology; 34 studies with 6463 patients, Radj2 =
      50.69%) or modified Rankin Scale score <=2 (year of publication, mean age,
      aneurysm morphology; 14 studies with 556 patients, Radj2 = 100%). CONCLUSIONS:
      Few clinically meaningful characteristics appear to be relevant as predictors of
      the selected measures of PED treatment success. Future studies should attempt to
      identify additional predictors while focusing on aneurysm morphology as a key
      predictor of PED outcomes.

PMID- 29588237
TI  - John C. Vangilder (1935-2007): Neurosurgical Leader and Founder of the Department
      of Neurosurgery at the University of Iowa.
AB  - John C. VanGilder, the former professor and chairman of neurosurgery at The
      University of Iowa died on August 27, 2007 after making a lasting impact to the
      field of neurosurgery both in the United States and abroad. In this manuscript,
      we review VanGilder's life and achievements. VanGilder was born in 1935 in West
      Virginia and received his undergraduate education at West Virginia University in
      Morgantown. He studied medicine at the University of West Virginia, completing
      his final 2 years at the University of Pittsburgh, and after serving in the U.S.
      military, completed his neurosurgical training at Washington University in St.
      Louis. He was appointed to faculty positions first at Yale University and later
      at The University of Iowa, where he became professor and later chairman of the
      Division of Neurosurgery. VanGilder also served as president of the Society of
      Neurological Surgeons (1997-1998), president of the Neurosurgical Society of
      America (1998-1999), chairman of the American Board of Neurological Surgery (1997
      1998), and vice president of the American Academy of Neurological Surgery. At The
      University of Iowa, VanGilder played a key role in the transition of the Division
      of Neurosurgery to a Department of Neurosurgery and mentored several
      neurosurgeons who would go on to become department chairmen or make other
      important neurosurgical contributions at other medical schools in the United
      States.

PMID- 29588238
TI  - Surgery for Multisegment Thoracolumbar Mild Osteoporotic Fractures: Revised
      Assessment System of Thoracolumbar Osteoporotic Fracture.
AB  - OBJECTIVE: To examine the Assessment System of Thoracolumbar Osteoporotic
      Fracture (ASTLOF), which can effectively guide the treatment of single-segmental
      thoracolumbar osteoporotic vertebral compression fractures but fails to guide the
      treatment of multisegmental thoracolumbar mild osteoporotic vertebral compression
      fracture (MSTMOVCF). METHODS: A prospective case series study was designed to
      enroll elderly patients with MSTMOVCF who had been treated with percutaneous
      kyphoplasty/percutaneous vertebroplasty (PKP/PVP) from June 2013 to June 2016.
      Surgery indication was based on revised ASTLOF. Visual analog scale and Oswestry
      Disability Index (ODI) scores were used to evaluate the postoperative improvement
      of back pain, and clinical effects were assessed according to the 36-Item Short
      Form Health Survey. Some imaging measures, such as height of anterior and middle
      column and Beck value, were measured before the operation and 12 months after the
      operation. Complications also were collected. RESULTS: A total of 193 patients
      underwent PKP/PVP surgery. At postoperative 2 days, 3 months, and 1-year follow
      up, whereas VAS and ODI scores decreased (P < 0.0001, for all) significantly as
      well as SF-36, the height of anterior and middle column increased (P < 0.0001,
      for all) compared with preoperation. Beck value at 1-year follow-up was greater
      than preoperation (P = 0.001). The improvement rate of ODI was 86.4 +/- 8.3%.
      CONCLUSIONS: Patients with MSTMOVCF who undergo surgery with PKP/PVP can achieve
      great clinical results. Patients with the sum of revised ASTLOF scores of
      multiple injured vertebrae >=5 should be recommended for surgery. The consistency
      and repeatability of the revised ASTLOF need further study.

PMID- 29588239
TI  - Coagulation Alteration and Deep Vein Thrombosis in Brain Tumor Patients During
      the Perioperative Period.
AB  - OBJECTIVE: To explore coagulation function in patients with brain tumors before
      and after craniotomy and tumor resection and to analyze its correlation with deep
      vein thrombosis (DVT). METHODS: This study enrolled 133 consecutive patients with
      brain tumors. Coagulation evaluation and limb venous ultrasonography were
      performed before and after surgery. Clinical characteristics and dynamic changes
      in coagulation parameters were recorded, and their correlations with DVT were
      analyzed. RESULTS: The incidence of postoperative DVT in patients with brain
      tumors was 10.5%. The average age of patients with DVT was older compared with
      patients without DVT (63.21 +/- 11.21 years vs. 50.24 +/- 11.95 years, P <
      0.001), and the incidence of hepatitis B (21% vs. 4%, P = 0.035) was higher in
      patients with DVT compared with patients without DVT. D-dimer and fibrinogen were
      the most variable parameters during the perioperative period. In patients with
      DVT, D-dimer levels displayed a "zigzagging-rise" trend and were significantly
      higher than levels in patients without DVT. Platelet levels displayed a "first
      descend-then-rise" trend and were significantly lower in patients with DVT on the
      second and third postoperative days. CONCLUSIONS: In patients with brain tumors,
      D-dimer and fibrinogen were elevated postoperatively, manifesting as
      hypercoagulability. Postoperative DVT was correlated with aging and hepatitis B.
      A "zigzagging-rise" trend of D-dimer and a "sharp-descent" trend of platelets in
      the early postoperative period might predict DVT in patients with brain tumors.

PMID- 29588240
TI  - Superficial Temporal Artery-Superior Cerebellar Artery Bypass with Anterior
      Petrosectomy.
AB  - BACKGROUND: Superficial temporal artery (STA) to superior cerebellar artery (SCA)
      bypass is associated with a relatively high risk of surgical complications, such
      as hematoma and/or edema caused by temporal lobe retraction. Therefore, the right
      side is typically used to avoid retraction of the left temporal lobe. In this
      report, we present a case of left STA-SCA bypass with anterior petrosectomy to
      avoid retraction of dominant-side temporal lobe and describe the surgical
      technique in detail. CASE DESCRIPTION: A 69-year-old man presented with gradual
      worsening of dysarthria and gait disturbance. Magnetic resonance imaging showed
      no signs of acute infarction, but digital subtraction angiography showed severe
      stenosis of basilar artery and faint flow in the distal basilar artery. On 3
      dimensional computed tomography angiography, posterior communicating arteries
      were not visualized; we could identify the left SCA, but not the right SCA.
      Despite dual antiplatelet therapy, a small fresh brainstem infarct was detected
      10 days after admission. To avert fatal brainstem infarction and further
      enlargement of the infarct, we performed left STA-SCA bypass with anterior
      petrosectomy to avoid retraction of the dominant-side temporal lobe.
      Postoperative imaging revealed no new lesions, such as infarction or temporal
      lobe contusional hematoma, and confirmed the patency of the bypass. Postoperative
      single-photon emission computed tomography demonstrated improved cerebral blood
      flow in the posterior circulation. The patient was transferred to another
      hospital for rehabilitation. CONCLUSIONS: This method helps minimize the risk of
      injury to the temporal lobe, especially that of the dominant side.

PMID- 29588242
TI  - Primary Spinal Malignant Mesothelioma: A Case Report and Literature Review.
AB  - BACKGROUND: Malignant mesotheliomas are aggressive and rapidly fatal neoplasms
      arising from the mesothelial cells. The most common sites of origin are the
      pleural and peritoneal cavities; the pericardium and the tunica vaginalis are
      infrequently involved, and malignant mesothelioma in the spinal canal is
      extremely rare. Here we report a case of primary spinal malignant mesothelioma.
      We also report the results of a literature search conducted in PubMed with
      specific key terms, inclusion criteria, and exclusion criteria, with a comparison
      of elected case studies and case series, and statistical analysis as appropriate.
      CASE DESCRIPTION: A 35-year-old man presented with a 3-month history of swelling
      and pain in the left lower extremity. Neurologic examination revealed a loss of
      sensation below the L5 dermatome. Magnetic resonance imaging (MRI) showed a mass
      at the L4-5 level. A diagnosis of schwannoma was suspected, and surgical
      resection was performed. Histopathological findings were consistent with
      sarcomatoid malignant mesothelioma. Thoracic and whole-abdomen computed
      tomography yielded normal results. The patient refused adjuvant radiotherapy or
      chemotherapy. Positron emission tomography-computed tomography performed at 3
      months postoperatively showed no abnormality. At 8 months postoperatively, the
      patient developed back pain and difficulty with defecation; MRI demonstrated
      tumor recurrence. During a second operation, invasion of the vertebra and cauda
      equina was noted. A subtotal resection was achieved, and the pain was partially
      alleviated. Two months later, the patient succumbed to a traffic accident.
      CONCLUSIONS: Spinal malignant mesothelioma is an extremely rare but highly
      aggressive entity. Preoperative identification is challenging, and definitive
      diagnosis depends on histopathological evidence. Surgical resection can help
      relieve the symptoms, but the overall prognosis is poor.

PMID- 29588241
TI  - Facet Joint Fixation and Anterior, Direct Lateral, and Transforaminal Lumbar
      Interbody Fusions for Treatment of Degenerative Lumbar Disc Diseases:
      Retrospective Cohort Study of a New Minimally Invasive Technique.
AB  - BACKGROUND: Anterior, direct lateral, and transforaminal lumbar interbody fusions
      (ALIF, DLIF, and TLIF) are usually combined with posterior fixation to treat
      degenerative spinal diseases. Outcomes of ALIF, TLIF, or DLIF combined with a new
      wedge-shaped interfacet cage plate have not been reported. We assessed early
      clinical outcomes of patients treated with interbody fusion and facet fixation
      using a titanium wedge-shaped cage plate. METHODS: This retrospective
      observational cohort study included patients (n = 80) who underwent 1-level
      interbody fusion and facet joint fixation via ALIF (n = 24) or DLIF (n = 26) with
      bilateral facet fixation or TLIF with ipsilateral pedicle screws and
      contralateral facet fixation (n = 30). Duration of surgery, estimated blood loss,
      pain (visual analog scale), Oswestry Disability Index (ODI) scores, and Macnab
      score were assessed up to 12 months after surgery. RESULTS: All patients had a
      significant decrease in pain scores (P < 0.01) and an increase in ODI scores (P <
      0.01), without significant differences between treatment groups. Most surgical
      outcomes were excellent or good (n = 75, 93.8%) with 5 patients (6.2%) having
      satisfactory outcomes. Within 2 months, all patients returned to their previous
      work (66, 82.5%) or lighter work (14, 17.5%). Two patients had fusion failure
      requiring reoperation. CONCLUSIONS: Facet fixation with the wedge-shaped cage
      plate was associated with minimal soft tissue damage and a low level of
      postoperative pain. ALIF, DLIF, and TLIF combined with this technique showed good
      early postoperative clinical and radiologic outcomes. Further studies are needed
      to assess long-term results and compare them with other fusion methods.

PMID- 29588243
TI  - Clinical Outcomes of Isolated Congenital Aqueductal Stenosis.
AB  - INTRODUCTION: Hydrocephalus due to congenital aqueductal stenosis (CAS) has
      significant long-term clinical implications. Previous reports on outcomes after
      treatment of congenital hydrocephalus are heterogenous and lack specificity for
      the subgroup of patients with isolated aqueductal stenosis. METHODS: An
      institutional surgical database was queried for the time period of 2005-2013 for
      patients with the diagnosis of isolated CAS and >2 years of clinical follow-up.
      Medical history and neurodevelopmental outcomes were recorded. RESULTS: The
      institutional cohort consisted of 41 patients with isolated CAS who underwent
      cerebrospinal fluid diversion. At a mean follow-up of 5.9 years, 48.8% carried a
      diagnosis of epilepsy and 68% were developmentally delayed. Four patients were
      diagnosed with cerebral palsy (9.8%). In total, 78% of patients were shunt
      dependent, and the remainder had patent third ventriculostomies. Only 32% of
      patients in our cohort were neurologically normal after long-term follow-up
      despite contemporary management. CONCLUSIONS: Regardless of the initial treatment
      strategy, the age at diagnosis, or the timing of cerebrospinal fluid diversion
      after birth, patients with aqueductal stenosis have high rates of epilepsy,
      neurodevelopmental delay, and educational difficulties, and few are
      neurologically normal despite contemporary management. Investigation into in
      utero identification and correction of hydrocephalus may result in improved
      outcomes and warrants further investigation.

PMID- 29588244
TI  - Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity.
AB  - BACKGROUND: Pheochromocytomas are uncommon neuroendocrine tumors of the adrenal
      medulla. Malignant behavior is seen in approximately 10% of these lesions,
      evidenced by distant metastasis to sites without chromaffin tissue. Here we
      report a rare case of intracranial epidural metastases of an adrenal
      pheochromocytoma in a 24-year-old man. CASE DESCRIPTION: The patient originally
      presented at age 10 years with adrenal pheochromocytoma and subsequently
      developed extensive metastatic bone and lung disease. He was monitored in the
      intervening years until recent imaging demonstrated an enlarging right parietal
      mass. On surgical resection of the parietal lesion, the tumor was highly
      vascularized and confined to the epidural space. CONCLUSIONS: To the best of our
      knowledge, this is the first reported case of metastatic epidural spread of
      pheochromocytoma without concomitant subdural or intraparenchymal extension.

PMID- 29588246
TI  - Drug survival of apremilast in patients treated for psoriasis in a real-world
      setting.

PMID- 29588245
TI  - Predicting Dural Tear in Compound Depressed Skull Fractures: A Prospective
      Multicenter Correlational Study.
AB  - BACKGROUND: Compound depressed skull fracture (DSF) is a neurosurgical emergency.
      Preoperative knowledge of dural status is indispensable for treatment decision
      making. This study aimed to determine predictors of dural tear from clinical and
      imaging characteristics in patients with compound DSF. METHODS: This prospective,
      multicenter correlational study in neurosurgical hospitals in Addis Ababa,
      Ethiopia, included 128 patients operated on from January 1, 2016, to October 31,
      2016. Clinical, imaging, and intraoperative findings were evaluated. Univariate
      and multivariate analyses were used to establish predictors of dural tear. A
      logistic regression model was developed to predict probability of dural tear.
      Model validation was done using the receiver operating characteristic curve.
      RESULTS: Dural tear was seen in 55.5% of 128 patients. Demographics, injury
      mechanism, clinical presentation, and site of DSF had no significant correlation
      with dural tear. In univariate and multivariate analyses, depth of fracture
      depression (odds ratio 1.3, P < 0.001), pneumocephalus (odds ratio 2.8, P =
      0.005), and brain contusions/intracerebral hematoma (odds ratio 5.5, P < 0.001)
      were significantly correlated with dural tear. We developed a logistic regression
      model (diagnostic test) to calculate probability of dural tear. Using the
      receiver operating characteristic curve, we determined the cutoff value for a
      positive test giving the highest accuracy to be 30% with a corresponding
      sensitivity of 93.0% and specificity of 43.9%. CONCLUSIONS: Dural tear in
      compound DSF can be predicted with 93.0% sensitivity using preoperative findings
      and may guide treatment decision making in resource-limited settings where risk
      of extensive cranial surgery outweighs the benefit.

PMID- 29588247
TI  - Low conversion rate of QuantiFERON-TB Gold screening tests in patients treated
      with tumor necrosis factor inhibitors: A retrospective cohort study identifying
      an important practice gap.

PMID- 29588248
TI  - Nonmalignant late cutaneous changes after allogeneic hematopoietic stem cell
      transplant in children.
AB  - BACKGROUND: There are limited pediatric data on nonmalignant cutaneous changes,
      including autoimmune conditions and permanent alopecia, after hematopoietic stem
      cell transplantation (HSCT). OBJECTIVE: We sought to characterize late cutaneous
      changes and associated risk factors after allogeneic HSCT in children. METHODS: A
      cross-sectional cohort study of pediatric HSCT recipients was performed at a
      single institution. All participants underwent a full skin examination. RESULTS:
      The median visit age was 13.8 years, with a median time post-HSCT of 3.6 years.
      Of 85 patients, 14% (n = 12) had vitiligo, 16% (n = 14) had
      psoriasis/sebopsoriasis, 25% (n = 21) had alopecia, and 6% (n = 5) had nail
      changes. Factors significantly associated with vitiligo included a history of
      chronic graft-versus-host disease (cGVHD), transplant indication of primary
      immunodeficiency, and younger age at transplant (<10 years of age). Fifty-two
      percent of patients with alopecia had androgenetic alopecia patterns. Factors
      significantly associated with alopecia included cGVHD, busulfan conditioning, and
      family history of early male pattern alopecia. All patients with nail changes had
      cGVHD. LIMITATIONS: The cross-sectional design did not allow time of onset
      identification. Histopathologic correlation was not performed. CONCLUSION:
      Pediatric HSCT recipients, particularly those with cGVHD, are at risk for
      developing nonmalignant late cutaneous changes.

PMID- 29588249
TI  - Risk of skin cancer in patients with HIV: A Danish nationwide cohort study.
AB  - BACKGROUND: The risk of skin cancer in patients with HIV has not been extensively
      studied. OBJECTIVE: We sought to determine the risk of skin cancer in patients
      with HIV and compare it with the risk in the background population. METHODS: In a
      matched, nationwide, population-based cohort study, we compared the risk of skin
      cancer in 4280 patients with HIV from the Danish HIV cohort study with a
      background population cohort, according to the level of immunosuppression and
      route of transmission. Primary outcomes were time to first basal cell carcinoma
      (BCC), squamous cell carcinoma (SCC), or malignant melanoma. RESULTS: Patients
      with HIV had an increased risk of BCC and SCC with incident rate ratios of 1.79
      (95% confidence interval 1.43-2.22) and 5.40 (95% confidence interval 3.07-9.52),
      respectively, compared with the background population. We observed no increased
      risk of malignant melanoma. Low nadir CD4 cell count was associated with an
      increased risk of SCC. The increased risk of BCC among patients with HIV was
      restricted to men who had sex with men. LIMITATIONS: This study was observational
      and included a small number of patients with melanoma. CONCLUSION: Patients with
      HIV have an increased risk of BCC and SCC. Low nadir, but not current, CD4 cell
      count as a marker of immunosuppression was associated with an increased risk of
      SCC.

PMID- 29588250
TI  - A Novel Role for Lymphotactin (XCL1) Signaling in the Nervous System: XCL1 Acts
      via its Receptor XCR1 to Increase Trigeminal Neuronal Excitability.
AB  - Chemokines are known to have a role in the nervous system, influencing a range of
      processes including the development of chronic pain. To date there are very few
      studies describing the functions of the chemokine lymphotactin (XCL1) or its
      receptor (XCR1) in the nervous system. We investigated the role of the XCL1-XCR1
      axis in nociceptive processing, using a combination of immunohistochemical,
      pharmacological and electrophysiological techniques. Expression of XCR1 in the
      rat mental nerve was elevated 3 days following chronic constriction injury (CCI),
      compared with 11 days post-CCI and sham controls. XCR1 co-existed with neuronal
      marker PGP9.5, leukocyte common antigen CD45 and Schwann cell marker S-100. In
      the trigeminal root and white matter of the brainstem, XCR1-positive cells co
      expressed the oligodendrocyte marker Olig2. In trigeminal subnucleus caudalis
      (Vc), XCR1 immunoreactivity was present in the outer laminae and was colocalized
      with vesicular glutamate transporter 2 (VGlut2), but not calcitonin gene-related
      peptide (CGRP) or isolectin B4 (IB4). Incubation of brainstem slices with XCL1
      induced activation of c-Fos, ERK and p38 in the superficial layers of Vc, and
      enhanced levels of intrinsic excitability. These effects were blocked by the XCR1
      antagonist viral CC chemokine macrophage inhibitory protein-II (vMIP-II). This
      study has identified for the first time a role for XCL1-XCR1 in nociceptive
      processing, demonstrating upregulation of XCR1 at nerve injury sites and
      identifying XCL1 as a modulator of central excitability and signaling via XCR1 in
      Vc, a key area for modulation of orofacial pain, thus indicating XCR1 as a
      potential target for novel analgesics.

PMID- 29588251
TI  - Effects of Class II-Selective Histone Deacetylase Inhibitor on Neuromuscular
      Function and Disease Progression in SOD1-ALS Mice.
AB  - Emerging evidence indicates that transcriptome alterations due to epigenetic
      deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase
      (HDAC) inhibitors delay ALS development in mice, but these compounds failed when
      tested in ALS patients. Possibly, lack of selectivity toward specific classes of
      HDACs weakens the therapeutic effects of pan-HDAC inhibitors. Here, we tested the
      effects of the HDAC Class II selective inhibitor MC1568 on disease evolution,
      motor neuron survival as well as skeletal muscle function in SOD1G93A mice. We
      report that HDACs did not undergo expression changes during disease evolution in
      isolated motor neurons of adult mice. Conversely, increase in specific Class II
      HDACs (-4, -5 and -6) occurs in skeletal muscle of mice with severe neuromuscular
      impairment. Importantly, treatment with MC1568 causes early improvement of motor
      performances that vanishes at later stages of disease. Notably, motor improvement
      is not paralleled by reduced motor neuron degeneration but by increased skeletal
      muscle electrical potentials, reduced activation of mir206/FGFBP1-dependent
      muscle reinnervation signaling, and increased muscle expression of myogenic
      genes.

PMID- 29588252
TI  - TLQP Peptides in Amyotrophic Lateral Sclerosis: Possible Blood Biomarkers with a
      Neuroprotective Role.
AB  - While the VGF-derived TLQP peptides have been shown to prevent neuronal
      apoptosis, and to act on synaptic strengthening, their involvement in Amyotrophic
      Lateral Sclerosis (ALS) remains unclarified. We studied human ALS patients'
      plasma (taken at early to late disease stages) and primary fibroblast cultures
      (patients vs controls), in parallel with SOD1-G93A transgenic mice (taken at pre
      , early- and late symptomatic stages) and the mouse motor neuron cell line (NSC
      34) treated with Sodium Arsenite (SA) to induce oxidative stress. TLQP peptides
      were measured by enzyme-linked immunosorbent assay, in parallel with gel
      chromatography characterization, while their localization was studied by
      immunohistochemistry. In controls, TLQP peptides, including forms compatible with
      TLQP-21 and 62, were revealed in plasma and spinal cord motor neurons, as well as
      in fibroblasts and NSC-34 cells. TLQP peptides were reduced in ALS patients'
      plasma starting in the early disease stage (14% of controls) and remaining so at
      the late stage (16% of controls). In mice, a comparable pattern of reduction was
      shown (vs wild type), in both plasma and spinal cord already in the pre
      symptomatic phase (about 26% and 70%, respectively). Similarly, the levels of
      TLQP peptides were reduced in ALS fibroblasts (31% of controls) and in the NSC-34
      treated with Sodium Arsenite (53% of decrease), however, the exogeneous TLQP-21
      improved cell viability (SA-treated cells with TLQP-21, vs SA-treated cells only:
      about 83% vs. 75%). Hence, TLQP peptides, reduced upon oxidative stress, are
      suggested as blood biomarkers, while TLQP-21 exerts a neuroprotective activity.

PMID- 29588253
TI  - Evaluation of a specialized filter-paper matrix for transportation of extended
      bovine semen to screen for bovine herpesvirus-1 by real-time PCR.
AB  - The extended frozen semen (EFS) batches produced from infectious bovine
      rhinotracheitis (IBR) sero-positive cattle and buffalo bulls housed in various
      semen stations in India are transported to the testing laboratory in liquid
      nitrogen (LN2) for screening bovine herpesvirus-1 (BoHV-1). This procedure is
      laborious and poses LN2 related hazards. An alternative logistics for
      transportation of samples was investigated. Use of Flinders Technology Associates
      (FTA(r)) elute card was evaluated for transportation of extended bovine semen to
      screen BoHV-1 DNA by real-time PCR targeting gB gene and the method was compared
      with the OIE approved Chelex resin based method. A protocol for extraction of
      BoHV-1 DNA from FTA(r) card spotted with extended semen was optimized. The viral
      DNA was found to be stable on FTA(r) card for at least 28 days when the cards are
      stored at 4 degrees -37  degrees C. The analytical sensitivity for the assay was
      determined using variable dilutions of BoHV-1 spiked semen and positive plasmid
      harbouring gB gene (97bp) spotted onto FTA(r) card and it was found to be 100.8
      TCID50/ml or 100 copies respectively in real-time PCR. The test could detect as
      low as 100.008 TCID50/ml or 1 copy of positive plasmid when more number of
      replicates (n = 6) of the same sample were tested. This sensitivity was found to
      be comparable to Chelex method and both the methods demonstrated a very strong
      correlation (r = 0.9774; 95% CI: 0.9620-0.9860) in terms of Ct value (p <
      0.0001). The diagnostic sensitivity and specificity of the FTA method in
      comparison to the Chelex method was 83.08% (95% CI: 71.73%-91.24%) and 93.23%
      (95% CI: 89.38%-96.01%) respectively when 316 samples were screened by both the
      methods. The degree of agreement between these two tests was good (Kappa value:
      0.738; 95% CI: 0.646-0.829). The method was found to be robust and highly
      repeatable in inter-assay and intra-assay precision testing. The result suggests
      that the FTA(r) card holds promise as an alternative system for transportation of
      EFS for downstream screening of BoHV-1 DNA.

PMID- 29588254
TI  - Efficiency of HIV-2 cultures from clinical isolates is enhanced after
      purification by anti-CD44 microbeads.
AB  - In-depth study of HIV often requires large stock of patients-derived viruses
      obtained through viral cultures. HIV cultures are currently limited by low
      recovery rates, especially when viral load is below 100,000 copies per mL. This
      is problematic for HIV-2 as most patients have spontaneously low to undetectable
      viremia. New approaches have been developed to enhance viral recovery rates but
      they are complex or costly to implement. We tested the impact of MUMACSTM
      VitalVirus Isolation Kit (Miltenyi), a HIV virions capture method using
      paramagnetic microbeads directed against CD44, a human glycoprotein present in
      HIV envelope. This method separates viruses from interfering proteins in 45 min,
      using a reduced sample volume (200 MUL versus 1000 MUL for classic culture
      assays). The impact of this purification method on virus recovery rate was
      assessed with 23 HIV-1 and 29 HIV-2 plasma samples with a wide range of viral
      loads, in comparison to a classic culture assay used routinely in our laboratory.
      For both HIV-1 and HIV-2, the culture identification delay was decreased using
      viral purification (<=7days in most cases). The recovery rate of cultures was
      improved for HIV-2 isolates (17/29 versus 8/29; p = 0.03) but not for HIV-1 (7/23
      versus 5/23; p = 0.74). Notably, HIV-2 isolates with viral loads over 10,000
      copies per mL were frequently recovered in culture (68% versus 32% without
      purification; p = 0.03). This marked improvement on HIV-2, but not on HIV-1,
      cultures is puzzling. CD44-microbeads may enable a close and prolonged contact
      between cells and viruses, and may thus overcome HIV-2 difficulties to infect
      target cells.

PMID- 29588255
TI  - Tumor-targeting CuS nanoparticles for multimodal imaging and guided photothermal
      therapy of lymph node metastasis.
AB  - : Precise diagnosis of lymph node metastasis to guide lymphadenectomy is highly
      important for gastric cancer therapy in clinics. Though surgical dissection of
      regional metastatic lymph nodes remains the only way for gastric cancer therapy,
      the extended dissection may cause unavoidable postoperative risk of
      complications. It is still lack of effective method enabling the accurate removal
      of metastatic gastric cancer cells in lymph nodes with minimum injuries to normal
      tissue. Herein, we report a new fluorescent copper sulfide (CuS) nanoparticle
      (RGD-CuS-Cy5.5) enabling both non-invasive multimodality imaging and targeting
      photothermal therapy (PTT) of metastatic gastric cancer cells in lymph nodes. We
      demonstrate that RGD-CuS-Cy5.5 can easily drain into sentinel lymph nodes (SLN)
      after injection into primary tumors, and selectively enter into metastatic
      gastric MNK45 tumor cells via alphavbeta3 integrin-mediated endocytosis. The
      resulting strong near-infrared (NIR) fluorescence and computed tomography (CT)
      contrast in metastatic SLN compared to normal SLN can precisely differentiate SLN
      metastasis of gastric cancers. Guided by the imaging, localized PTT with RGD-CuS
      Cy5.5 is conducted upon irradiation with an 808 nm laser, resulting in complete
      removal of metastatic gastric tumor cells in SLN without obvious toxicity.
      Moreover, RGD-CuS-Cy5.5 can also allow for the rapid and non-invasive self
      monitoring of PTT efficacy against metastatic SLNs in living mice. This study
      highlights the potential of using RGD-CuS-Cy5.5 for imaging-guided and targeting
      PTT of SLN metastasis in vivo, which may be applicable for the metastatic gastric
      cancer therapy in clinics. STATEMENT OF SIGNIFICANCE: RGD-CuS-Cy5.5 nanoparticles
      possess NIR fluorescence and CT signals for in vivo bimodality imaging of lymph
      node metastasis. Strong photothermal property under irradiation at 808 nm for
      efficient PTT. Easy drain into sentinel lymph nodes and selective enter
      metastatic gastric cancer cells via alphavbeta3 integrin-mediated endocytosis.
      Rapid and non-invasive monitoring of therapeutic efficacy against lymph node
      metastasis.

PMID- 29588259
TI  - A Rare Case of Incidental Common Bile Duct Adenoma-Endoscopic Ultrasound
      Evaluation

PMID- 29588258
TI  - The effect of a pre-procedure information video on anxiety levels in patients
      undergoing hysterosalpingography: A prospective case-control study
AB  - Objective: To evaluate the effect of a pre-procedural information video on
      anxiety levels in patients undergoing hysterosalpingography (HSG). Material and
      Methods: Among a total of 131 primary or secondary infertile patients, 66 were
      shown an information video and 67 control patients received standard care between
      August 2014 and January 2016. The video included information on the procedure,
      personnel, and the room for the procedure; the video was shown on the morning of
      the procedure. Patients were randomized using the complete randomization
      technique through which patients were included in the study and control groups
      week by week, randomly. The Beck Anxiety Inventory scale was conducted to the
      patients one hour before the procedure. Results: There were no differences in
      demographic data. The history of previous gynecologic operations was higher in
      the control group. The Beck Anxiety score was significantly lower in the study
      group compared with the control group (6 vs 10). Conclusion: Our findings suggest
      that as an easy intervention to implement, a pre-procedural video education may
      be a beneficial tool for the management of HSG-related anxiety.

PMID- 29588260
TI  - A Rare Cause of Left Ventricular Mass: Cardiac Hemangioma

PMID- 29588261
TI  - Complete Penile Duplication with Structurally Normal Penises: A Case Report
AB  - BACKGROUND: Diphallia is a very rare anomaly and seen once in every 5.5 million
      live births. True diphallia with normal penile structures is extremely rare.
      Surgical management for patients with complete penile duplication without any
      penile or urethral pathology is challenging. CASE REPORT: A 4-year-old boy
      presented with diphallia. Initial physical examination revealed first physical
      examination revealed complete penile duplication, urine flow from both penises,
      meconium flow from right urethra, and anal atresia. Further evaluations showed
      double colon and rectum, double bladder, and large recto-vesical fistula. Two
      cavernous bodies and one spongious body were detected in each penile body.
      Surgical treatment plan consisted of right total penectomy and end-to-side
      urethra-urethrostomy. No postoperative complications and no voiding dysfunction
      were detected during the 18 months follow-up. CONCLUSION: Penile duplication is a
      rare anomaly, which presents differently in each patient. Because of this, the
      treatment should be individualized and end-to-side urethra-urethrostomy may be an
      alternative to removing posterior urethra. This approach eliminates the risk of
      damaging prostate gland and sphincter.

PMID- 29588262
TI  - Analyzing the etiology behind mortality associated with antepartum, intrapartum,
      and post-partum cases in a tertiary care teaching hospital of West Bengal
AB  - OBJECTIVE: The study was undertaken to understand the causes and circumstances of
      maternal deaths in West Bengal. MATERIAL AND METHODS: One hundred ten maternal
      deaths were reported during the period December 2010 through June 2012 in the
      Maternity Ward of Medical College and Hospitals, West Bengal. These deaths were
      reviewed using a facility-based Maternal Death Review protocol. The number and
      percentages were calculated and binary logistic regression analysis was
      performed. RESULTS: The majority of the deaths occurred in the 20-24 years' age
      group, those with Hindu religion, in the first and second gravida, and the
      postpartum period. One third of mothers had cesarean sections. The majority
      (78.2%) of deaths were among referred cases. Eclampsia was the leading cause of
      maternal death (29.1%). Approximately half of the deceased women sought care
      after 10 hours of developing complications. More than one-third of maternal
      deaths were registered with type 1 delays. CONCLUSION: Our study demonstrates
      that maternal deaths occurred among young women, referred cases, with cesarean
      sections and type 1 delays. We recommend that imparting basic skills and
      improving awareness to the community about the danger signs of pregnancy could be
      an effective measure to detect maternal complications at an earlier stage.

PMID- 29588263
TI  - Injury of the Prefrontocaudate Tract in a Patient with a Bilateral Caudate
      Infarct

PMID- 29588264
TI  - Prognostic effect of isolated paraaortic nodal spread in endometrial cancer
AB  - Objective: To evaluate the prognostic effect of isolated paraaortic lymph node
      metastasis in endometrial cancer (EC). Material and Methods: This retrospective
      study included patients with FIGO 2009 stage IIIC2 disease due to isolated
      paraaortic lymph node metastasis (LNM). Patients with sarcomatous histology,
      synchronous gynecologic cancers and patients with concurrent pelvic lymph node
      metastases or patients that have intraabdominal tumor spread were excluded.
      Kaplan-Meier method was used for calculation of progression free survival (PFS)
      and overall survival. Results: One thousand six hundred and fourteen patients
      were operated for EC during study period. Nine hundred and sixty-one patients
      underwent lymph node dissection and 25 (2.6%) were found to have isolated LNM in
      paraaortic region and these constituted the study cohort. Twenty (80%) patients
      had endometrioid EC. Median number of retrieved lymph nodes from pelvic region
      and paraaortic region was 21.5 (range: 5-41) and 34.5 (range: 1-65),
      respectively. Median number of metastatic paraaortic nodes was 1 (range: 1-32).
      The median follow-up time was 15 months (range 5-94). Seven (28%) patients
      recurred after a median of 20 months (range, 3-99) from initial surgery. Three
      patients recurred only in pelvis, one patient had upper abdominal spread and 3
      had isolated extraabdominal recurrence. Involvement of uterine serosa, positive
      peritoneal cytology and presence of adnexal metastasis were significantly
      associated with diminished PFS (p<0.05). Conclusion: The presence of serosal
      involvement or adnexal involvement is as important as gross peritoneal spread and
      is related with poor survival in patients with isolated paraaortic nodal spread
      in EC. Chemotherapy should be the mainstay of treatment in this patient cohort
      which may eradicate systemic tumor spread.

PMID- 29588265
TI  - Double Pyramidal Lobe of the Thyroid Gland.

PMID- 29588266
TI  - New Hypothesis and Alternative Approach for Imaging Neuronal Function and
      Metabolic Activity Based on Redox-Status

PMID- 29588267
TI  - The SMART Study, a Mobile Health and Citizen Science Methodological Platform for
      Active Living Surveillance, Integrated Knowledge Translation, and Policy
      Interventions: Longitudinal Study.
AB  - BACKGROUND: Physical inactivity is the fourth leading cause of death worldwide,
      costing approximately US $67.5 billion per year to health care systems. To curb
      the physical inactivity pandemic, it is time to move beyond traditional
      approaches and engage citizens by repurposing sedentary behavior (SB)-enabling
      ubiquitous tools (eg, smartphones). OBJECTIVE: The primary objective of the
      Saskatchewan, let's move and map our activity (SMART) Study was to develop a
      mobile and citizen science methodological platform for active living
      surveillance, knowledge translation, and policy interventions. This methodology
      paper enumerates the SMART Study platform's conceptualization, design,
      implementation, data collection procedures, analytical strategies, and potential
      for informing policy interventions. METHODS: This longitudinal investigation was
      designed to engage participants (ie, citizen scientists) in Regina and Saskatoon,
      Saskatchewan, Canada, in four different seasons across 3 years. In spring 2017,
      pilot data collection was conducted, where 317 adult citizen scientists (>=18
      years) were recruited in person and online. Citizen scientists used a custom
      built smartphone app, Ethica (Ethica Data Services Inc), for 8 consecutive days
      to provide a complex series of objective and subjective data. Citizen scientists
      answered a succession of validated surveys that were assigned different
      smartphone triggering mechanisms (eg, user-triggered and schedule-triggered). The
      validated surveys captured physical activity (PA), SB, motivation, perception of
      outdoor and indoor environment, and eudaimonic well-being. Ecological momentary
      assessments were employed on each day to capture not only PA but also physical
      and social contexts along with barriers and facilitators of PA, as relayed by
      citizen scientists using geo-coded pictures and audio files. To obtain a
      comprehensive objective picture of participant location, motion, and compliance,
      6 types of sensor-based (eg, global positioning system and accelerometer) data
      were surveilled for 8 days. Initial descriptive analyses were conducted using geo
      coded photographs and audio files. RESULTS: Pictures and audio files (ie,
      community voices) showed that the barriers and facilitators of active living
      included intrinsic or extrinsic motivations, social contexts, and outdoor or
      indoor environment, with pets and favorable urban design featuring as the
      predominant facilitators, and work-related screen time proving to be the primary
      barrier. CONCLUSIONS: The preliminary pilot results show the flexibility of the
      SMART Study surveillance platform in identifying and addressing limitations based
      on empirical evidence. The results also show the successful implementation of a
      platform that engages participants to catalyze policy interventions. Although
      SMART Study is currently geared toward surveillance, using the same platform,
      active living interventions could be remotely implemented. SMART Study is the
      first mobile, citizen science surveillance platform utilizing a rigorous,
      longitudinal, and mixed-methods investigation to temporally capture behavioral
      data for knowledge translation and policy interventions.

PMID- 29588268
TI  - Satisfying Product Features of a Fall Prevention Smartphone App and Potential
      Users' Willingness to Pay: Web-Based Survey Among Older Adults.
AB  - BACKGROUND: Prohibiting falls and fall-related injuries is a major challenge for
      health care systems worldwide, as a substantial proportion of falls occur in
      older adults who are previously known to be either frail or at high risk for
      falls. Hence, preventive measures are needed to educate and minimize the risk for
      falls rather than just minimize older adults' fall risk. Health apps have the
      potential to address this problem, as they enable users to self-assess their
      individual fall risk. OBJECTIVE: The objective of this study was to identify
      product features of a fall prevention smartphone app, which increase or decrease
      users' satisfaction. In addition, willingness to pay (WTP) was assessed to
      explore how much revenue such an app could generate. METHODS: A total of 96
      participants completed an open self-selected Web-based survey. Participants
      answered various questions regarding health status, subjective and objective fall
      risk, and technical readiness. Seventeen predefined product features of a fall
      prevention smartphone app were evaluated twice: first, according to a functional
      (product feature is implemented in the app), and subsequently by a dysfunctional
      (product feature is not implemented in the app) question. On the basis of the
      combination of answers from these 2 questions, the product feature was assigned
      to a certain category (must-be, attractive, one-dimensional, indifferent, or
      questionable product feature). This method is widely used in user-oriented
      product development and captures users' expectations of a product and how their
      satisfaction is influenced by the availability of individual product features.
      RESULTS: Five product features were identified to increase users' acceptance,
      including (1) a checklist of typical tripping hazards, (2) an emergency guideline
      in case of a fall, (3) description of exercises and integrated workout plans that
      decrease the risk of falling, (4) inclusion of a continuous workout program, and
      (5) cost coverage by health insurer. Participants' WTP was assessed after all 17
      product features were rated and revealed a median monthly payment WTP rate of
      ?5.00 (interquartile range 10.00). CONCLUSIONS: The results show various
      motivating product features that should be incorporated into a fall prevention
      smartphone app. Results reveal aspects that fall prevention and intervention
      designers should keep in mind to encourage individuals to start joining their
      program and facilitate long-term user engagement, resulting in a greater interest
      in fall risk prevention.

PMID- 29588269
TI  - Developing a Shared Patient-Centered, Web-Based Medication Platform for Type 2
      Diabetes Patients and Their Health Care Providers: Qualitative Study on User
      Requirements.
AB  - BACKGROUND: Information technology tools such as shared patient-centered, Web
      based medication platforms hold promise to support safe medication use by
      strengthening patient participation, enhancing patients' knowledge, helping
      patients to improve self-management of their medications, and improving
      communication on medications among patients and health care professionals (HCPs).
      However, the uptake of such platforms remains a challenge also due to inadequate
      user involvement in the development process. Employing a user-centered design
      (UCD) approach is therefore critical to ensure that user' adoption is optimal.
      OBJECTIVE: The purpose of this study was to identify what patients with type 2
      diabetes mellitus (T2DM) and their HCPs regard necessary requirements in terms of
      functionalities and usability of a shared patient-centered, Web-based medication
      platform for patients with T2DM. METHODS: This qualitative study included focus
      groups with purposeful samples of patients with T2DM (n=25), general
      practitioners (n=13), and health care assistants (n=10) recruited from regional
      health care settings in southwestern Germany. In total, 8 semistructured focus
      groups were conducted. Sessions were audio- and video-recorded, transcribed
      verbatim, and subjected to a computer-aided qualitative content analysis.
      RESULTS: Appropriate security and access methods, supported data entry, printing,
      and sending information electronically, and tracking medication history were
      perceived as the essential functionalities. Although patients wanted automatic
      interaction checks and safety alerts, HCPs on the contrary were concerned that
      unspecific alerts confuse patients and lead to nonadherence. Furthermore, HCPs
      were opposed to patients' ability to withhold or restrict access to information
      in the platform. To optimize usability, there was consensus among participants to
      display information in a structured, chronological format, to provide information
      in lay language, to use visual aids and customize information content, and align
      the platform to users' workflow. CONCLUSIONS: By employing a UCD, this study
      provides insight into the desired functionalities and usability of patients and
      HCPs regarding a shared patient-centered, Web-based medication platform, thus
      increasing the likelihood to achieve a functional and useful system. Substantial
      and ongoing engagement by all intended user groups is necessary to reconcile
      differences in requirements of patients and HCPs, especially regarding medication
      safety alerts and access control. Moreover, effective training of patients and
      HCPs on medication self-management (support) and optimal use of the tool will be
      a prerequisite to unfold the platform's full potential.

PMID- 29588270
TI  - Impacts of Urban Agriculture on the Determinants of Health: Scoping Review
      Protocol.
AB  - BACKGROUND: Since the 1990s, urban agriculture (UA) has contributed to improving
      food security in low- and middle- income countries. Now, it is implemented as a
      multifunctional intervention that can influence various determinants of health
      (eg, food security, social relationships). Studies of interest stem from several
      research disciplines, use a wide range of methods, and show results that are
      sometimes inconsistent. Current studies have not summarized the overall effects
      of UA on health and its determinants. OBJECTIVE: The objective of this protocol
      is to develop a research strategy for a scoping review that characterizes studies
      of beneficial and adverse impacts of UA on health and its determinants in a wide
      range of disciplines. METHODS: Initially, with the help of a library specialist,
      a list of publications will be obtained through a systematic search of seven
      electronic bibliographic databases: PubMed, Embase, MEDLINE (Embase), CINAHL Plus
      with full text, Academic Search Premier (EBSCO host), CAB Abstract (Ovid), and
      Web of Science. Secondly, a three-step screening by two independent reviewers
      will lead to a list of relevant publications that meet eligibility and inclusion
      criteria. Finally, data on the bibliography, type of participants, type of study,
      results of study, and countries will be extracted from included articles and
      analyzed to be presented in a peer-reviewed article. RESULTS: The findings are
      expected to identify research gaps that will inform needs for UA research in
      specific fields (eg, mental health), among certain population groups (eg, adults)
      or within different economic contexts (eg, low-, middle-, or high-income
      countries). Furthermore, the findings are expected to identify knowledge gaps and
      direct future research needs. CONCLUSIONS: This is an original study that seeks
      to integrate beneficial and adverse effects of UA on health at different level of
      influence (individuals, households, and community) in order to facilitate a
      better understanding of UA impacts. This protocol is a first of its kind and is
      expected to lead to a characterization of UA impacts based on sociodemographic
      profiles of participants and income levels of the studied countries. This will be
      relevant for policy makers and UA practitioners.

PMID- 29588271
TI  - Development of an Exergame to Deliver a Sustained Dose of High-Intensity
      Training: Formative Pilot Randomized Trial.
AB  - BACKGROUND: Sport science can play a critical role in reducing health
      inequalities. The inverse relationship between life expectancy, cardiorespiratory
      fitness, and socioeconomic status could be addressed by performing high-intensity
      training (HIT), delivered in a class salient and accessible approach.
      Commercially available exergames have shown encouraging compliance rates but are
      primarily designed for entertainment purposes rather than focusing on health
      related outcomes. A serious game tailored toward delivering an exercise stimulus,
      while reducing the aversive protocols associated with HIT, could be beneficial to
      engage and improve health outcomes in socially deprived males. OBJECTIVE: The
      aims of this study were to develop an exergame capable of delivering HIT and
      evaluate the effect on selected health outcomes in men recruited in regions of
      socioeconomic deprivation. METHODS: We conducted an exploratory trial in our
      target population, and participants were allocated to intervention (n=14) or
      control groups (n=10) by third-party minimization. The intervention was a 6-week
      training program consisting of three sessions of exergaming per week. The
      sessions involved a structured warm-up, then brief intermittent repetitions in
      the form of boxing rounds (10 s, 20 s, and 30 s) against their peers with a
      work/rest ratio of 0.25. RESULTS: Retention to the intervention was 87.5%
      (21/24). Over the duration of the intervention, session attendance was 67.5%
      (170/252); repetition mean and peak heart rates (% of maximal) and session
      ratings of perceived exertion (AU, arbitrary units) were 86.3 (5.4%), 89.9
      (6.1%), and 7.5 (2.2 AU), respectively. The effect of the intervention, when
      compared with the control, was a likely small beneficial improvement in predicted
      maximum oxygen consumption (VO2 max, 3.0; 90% confidence limits +/-2.6%). Effects
      on body mass, waist circumference, and blood pressure were either trivial or
      unclear. CONCLUSIONS: Over the 6-week intervention, the exergame delivered a
      consistent and sustained dose of HIT, with some beneficial effects on aerobic
      fitness in the target population. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT03477773; https://clinicaltrials.gov/ct2/show/NCT03477773 (Archived by WebCite
      at http://www.webcitation.org/6yDLgVs35).

PMID- 29588272
TI  - Integration of a Technology-Based Mental Health Screening Program Into Routine
      Practices of Primary Health Care Services in Peru (The Allillanchu Project):
      Development and Implementation.
AB  - BACKGROUND: Despite their high prevalence and significant burden, mental
      disorders such as depression remain largely underdiagnosed and undertreated.
      OBJECTIVE: The aim of the Allillanchu Project was to design, develop, and test an
      intervention to promote early detection, opportune referral, and access to
      treatment of patients with mental disorders attending public primary health care
      (PHC) services in Lima, Peru. METHODS: The project had a multiphase design:
      formative study, development of intervention components, and implementation. The
      intervention combined three strategies: training of PHC providers (PHCPs), task
      shifting the detection and referral of mental disorders, and a mobile health
      (mHealth) component comprising a screening app followed by motivational and
      reminder short message service (SMS) to identify at-risk patients. The
      intervention was implemented by 22 PHCPs from five health centers, working in
      antenatal care, tuberculosis, chronic diseases, and HIV or AIDS services.
      RESULTS: Over a period of 9 weeks, from September 2015 to November 2015, 733
      patients were screened by the 22 PHCPs during routine consultations, and 762
      screening were completed in total. The chronic diseases (49.9%, 380/762) and
      antenatal care services (36.7%, 380/762) had the higher number of screenings.
      Time constraints and workload were the main barriers to implementing the
      screening, whereas the use of technology, training, and supervision of the PHCPs
      by the research team were identified as facilitators. Of the 733 patients, 21.7%
      (159/733) screened positively and were advised to seek specialized care. Out of
      the 159 patients with a positive screening result, 127 had a follow-up interview,
      72.4% (92/127) reported seeking specialized care, and 55.1% (70/127) stated
      seeing a specialist. Both patients and PHCPs recognized the utility of the
      screening and identified some key challenges to its wider implementation.
      CONCLUSIONS: The use of a screening app supported by training and supervision is
      feasible and uncovers a high prevalence of unidentified psychological symptoms in
      primary care. To increase its sustainability and utility, this procedure can be
      incorporated into the routine practices of existing health care services,
      following tailoring to the resources and features of each service. The early
      detection of psychological symptoms by a PHCP within a regular consultation,
      followed by adequate advice and support, can lead to a significant percentage of
      patients accessing specialized care and reducing the treatment gap of mental
      disorders.

PMID- 29588274
TI  - Digital Transformation and Disruption of the Health Care Sector: Internet-Based
      Observational Study.
AB  - BACKGROUND: Digital innovation, introduced across many industries, is a strong
      force of transformation. Some industries have seen faster transformation, whereas
      the health care sector only recently came into focus. A context where digital
      corporations move into health care, payers strive to keep rising costs at bay,
      and longer-living patients desire continuously improved quality of care points to
      a digital and value-based transformation with drastic implications for the health
      care sector. OBJECTIVE: We tried to operationalize the discussion within the
      health care sector around digital and disruptive innovation to identify what type
      of technological enablers, business models, and value networks seem to be
      emerging from different groups of innovators with respect to their digital
      transformational efforts. METHODS: From the Forbes 2000 and CBinsights databases,
      we identified 100 leading technology, life science, and start-up companies active
      in the health care sector. Further analysis identified projects from these
      companies within a digital context that were subsequently evaluated using the
      following criteria: delivery of patient value, presence of a comprehensive and
      distinctive underlying business model, solutions provided, and customer needs
      addressed. RESULTS: Our methodological approach recorded more than 400 projects
      and collaborations. We identified patterns that show established corporations
      rely more on incremental innovation that supports their current business models,
      while start-ups engage their flexibility to explore new market segments with
      notable transformations of established business models. Thereby, start-ups offer
      higher promises of disruptive innovation. Additionally, start-ups offer more
      diversified value propositions addressing broader areas of the health care
      sector. CONCLUSIONS: Digital transformation is an opportunity to accelerate
      health care performance by lowering cost and improving quality of care. At an
      economic scale, business models can be strengthened and disruptive innovation
      models enabled. Corporations should look for collaborations with start-up
      companies to keep investment costs at bay and off the balance sheet. At the same
      time, the regulatory knowledge of established corporations might help start-ups
      to kick off digital disruption in the health care sector.

PMID- 29588275
TI  - Differential ubiquitination in NETs regulates macrophage responses in systemic
      lupus erythematosus.
AB  - OBJECTIVES: To assess if ubiquitinated proteins potentially present in neutrophil
      extracellular traps (NETs) can modify cellular responses and induce inflammatory
      mechanisms in patients with systemic lupus erythematosus (SLE) and healthy
      subjects. MATERIALS AND METHODS: We studied 74 subjects with SLE and 77 healthy
      controls. Neutrophils and low-density granulocytes were isolated, and NETs were
      induced. Ubiquitin content was quantified in NETs by western blot analysis, ELISA
      and immunofluorescence microscopy, while ubiquitination of NET proteins was
      assessed by immunoprecipitation. Monocyte-derived macrophages from SLE and
      controls were isolated and stimulated with NETs or ubiquitin. Calcium flux and
      cytokine synthesis were measured following these stimuli. RESULTS: NETs contain
      ubiquitinated proteins, with a lower expression of polyubiquitinated proteins in
      subjects with SLE than in controls. Myeloperoxidase (MPO) is present in
      ubiquitinated form in NETs. Patients with SLE develop antiubiquitinated MPO
      antibodies, and titres positively correlate with Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) score (P<0.01), and negatively correlate with
      complement components (P<0.01). Stimulation of monocyte-derived macrophages with
      NETs or with ubiquitin led to enhanced calcium flux. In addition, stimulation
      with NETs led to enhanced cytokine (tumour necrosis factor-alpha and interleukin
      10) production in macrophages from patients with SLE when compared with controls,
      which was hampered by inhibition of NET internalisation by macrophages.
      CONCLUSION: This is the first study to find ubiquitinated proteins in NETs, and
      evidence for adaptive immune responses directed towards ubiquitinated NET
      proteins in SLE. The distinct differences in ubiquitin species profile in NETs
      compared with healthy controls may contribute to dampened anti-inflammatory
      responses observed in SLE. These results also support a role for extracellular
      ubiquitin in inflammation in SLE.

PMID- 29588273
TI  - Monitoring Energy Balance in Breast Cancer Survivors Using a Mobile App:
      Reliability Study.
AB  - BACKGROUND: The majority of breast cancer survivors do not meet recommendations
      in terms of diet and physical activity. To address this problem, we developed a
      mobile health (mHealth) app for assessing and monitoring healthy lifestyles in
      breast cancer survivors, called the Energy Balance on Cancer (BENECA) mHealth
      system. The BENECA mHealth system is a novel and interactive mHealth app, which
      allows breast cancer survivors to engage themselves in their energy balance
      monitoring. BENECA was designed to facilitate adherence to healthy lifestyles in
      an easy and intuitive way. OBJECTIVE: The objective of the study was to assess
      the concurrent validity and test-retest reliability between the BENECA mHealth
      system and the gold standard assessment methods for diet and physical activity.
      METHODS: A reliability study was conducted with 20 breast cancer survivors. In
      the study, tri-axial accelerometers (ActiGraphGT3X+) were used as gold standard
      for 8 consecutive days, in addition to 2, 24-hour dietary recalls, 4 dietary
      records, and sociodemographic questionnaires. Two-way random effect intraclass
      correlation coefficients, a linear regression-analysis, and a Passing-Bablok
      regression were calculated. RESULTS: The reliability estimates were very high for
      all variables (alpha>=.90). The lowest reliability was found in fruit and
      vegetable intakes (alpha=.94). The reliability between the accelerometer and the
      dietary assessment instruments against the BENECA system was very high
      (intraclass correlation coefficient=.90). We found a mean match rate of 93.51%
      between instruments and a mean phantom rate of 3.35%. The Passing-Bablok
      regression analysis did not show considerable bias in fat percentage, portions of
      fruits and vegetables, or minutes of moderate to vigorous physical activity.
      CONCLUSIONS: The BENECA mHealth app could be a new tool to measure energy balance
      in breast cancer survivors in a reliable and simple way. Our results support the
      use of this technology to not only to encourage changes in breast cancer
      survivors' lifestyles, but also to remotely monitor energy balance. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02817724;
      https://clinicaltrials.gov/ct2/show/NCT02817724 (Archived by WebCite at
      http://www.webcitation.org/6xVY1buCc).

PMID- 29588276
TI  - Defining refractory rheumatoid arthritis.
AB  - While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed
      outcomes of people with rheumatoid arthritis (RA), a proportion of patients are
      refractory to multiple bDMARDs. Definitions of refractory RA thus far have been
      arbitrary, and outcome data and impact of such cohorts remain limited.
      Extrapolation from randomised controlled trial and some real-life data suggest
      approximately 20% progress onto a third bDMARD with a more modest proportion
      failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA
      disease and proposes key principles to accurately identify refractory cohorts.
      These include demonstrating presence of persistent inflammation despite multiple
      therapies and acknowledging development of antidrug antibody. Potential basis of
      refractory disease is summarised, and suggestions for an initial approach in the
      future evaluation of refractory disease are offered. Specific investigation of
      refractory RA disease is necessary to inform the clinical need and provide a
      basis for robust investigation of underlying mechanisms.

PMID- 29588279
TI  - David Oliver: Moral distress in hospital doctors.

PMID- 29588277
TI  - Tolerogenic properties of the Fc portion of IgG and its relevance to the
      treatment and management of hemophilia
AB  - Hemophilia, or inherited genetic deficiencies in coagulation factors, results in
      uncontrolled bleeding requiring replacement therapy with recombinant proteins
      given preventively or on demand. However, a major problem with these approaches
      is the potential for development of immune responses to the administered proteins
      due to the underlying genetic deficiency of the factor(s) throughout life. As
      such, there is great interest in developing strategies that avoid immunogenicity
      and induce immune tolerance. Recently, recombinant factor VIII (rFVIII) and rFIX
      fused to the crystallizable fragment (Fc) domain of immunoglobulin G (IgG) have
      been developed as therapeutic agents for hemophilia A and B, respectively.
      Although it is well known that the possession of an Fc domain confers IgG's
      longer-lasting circulating half-life, it is not generally appreciated that the Fc
      domain also confers immunoregulatory properties that are associated with the
      induction of tolerance. Here, we review some of the latest advances in our
      understanding of the tolerogenic abilities of IgG Fc and the impact of Fc-fusion
      proteins of rFVIII on the treatment of hemophilia.

PMID- 29588278
TI  - A single-cell hematopoietic landscape resolves 8 lineage trajectories and defects
      in Kit mutant mice.
AB  - Hematopoietic stem and progenitor cells (HSPCs) maintain the adult blood system,
      and their dysregulation causes a multitude of diseases. However, the
      differentiation journeys toward specific hematopoietic lineages remain ill
      defined, and system-wide disease interpretation remains challenging. Here, we
      have profiled 44 802 mouse bone marrow HSPCs using single-cell RNA sequencing to
      provide a comprehensive transcriptional landscape with entry points to 8
      different blood lineages (lymphoid, megakaryocyte, erythroid, neutrophil,
      monocyte, eosinophil, mast cell, and basophil progenitors). We identified a
      common basophil/mast cell bone marrow progenitor and characterized its molecular
      profile at the single-cell level. Transcriptional profiling of 13 815 HSPCs from
      the c-Kit mutant (W41/W41) mouse model revealed the absence of a distinct mast
      cell lineage entry point, together with global shifts in cell type abundance.
      Proliferative defects were accompanied by reduced Myc expression. Potential
      compensatory processes included upregulation of the integrated stress response
      pathway and downregulation of proapoptotic gene expression in erythroid
      progenitors, thus providing a template of how large-scale single-cell
      transcriptomic studies can bridge between molecular phenotypes and quantitative
      population changes.

PMID- 29588280
TI  - Clinical presentation of Lyme disease in the higher-risk region of Quebec: a
      retrospective descriptive study.
AB  - BACKGROUND: Lyme disease is emerging in Canada. This study aimed to describe the
      use of serologic testing for the disease in the La Pommeraie health region in
      southern Quebec between 2012 and 2015 and to describe the clinical presentation
      of laboratory-confirmed cases. METHODS: The medical charts of all patients
      investigated for Lyme disease at the Brome-Missisquoi-Perkins Hospital's
      laboratory between 2012 and 2015 were reviewed for results of serologic testing.
      Laboratory diagnosis was based on 2-tiered testing: cases had to have positive
      results of both the enzyme immunoassay and the Western blot test (IgM or IgG). We
      collected data on clinical presentation for patients assessed at the hospital or
      at the La Pommeraie Family Medicine Unit. RESULTS: Over the study period, 720
      patients were investigated for Lyme disease. There was a more than fivefold
      increase in requests for serologic testing from 2012 (53) to 2015 (273). The
      number of confirmed cases increased from 2012 (3) to 2013 (19) and remained
      stable thereafter (19 in 2014, 18 in 2015). Fifty patients were positive for IgM
      with or without IgG positivity, and 9 patients were IgG-positive only. Chart
      reviews were completed for 278 of the 720 patients, including 38 of the 59
      laboratory-confirmed cases. Among the 29 IgM-positive patients, the most common
      symptoms were fever (17 patients [59%]), fatigue (14 [48%]), myalgia (12 [41%])
      and headaches (10 [34%]). Twenty-three (79%) had some cutaneous manifestation,
      including specifically erythema migrans (14 [48%]). A tick bite was reported by
      11 patients (38%). Of the 44 patients in the entire study population who
      presented with erythema migrans, 15 (34%) had confirmed Lyme disease.
      INTERPRETATION: Requests for serologic testing for Lyme disease increased in the
      La Pommeraie health region over recent years. Cutaneous manifestations, fever and
      myalgia were the most common symptoms of IgM-positive cases. Most patients did
      not report a tick bite.

PMID- 29588281
TI  - When a transfusion in an emergency service is not really urgent: hyperhaemolysis
      syndrome in a child with sickle cell disease.
AB  - A 13-month-old boy with sickle cell disease (SCD) from Equatorial Guinea, who had
      recently arrived in Spain, presented with fever. He had suffered from malaria and
      had received a blood transfusion. Following physical examination and
      complementary tests, intravenous antibiotics and a red blood cell (RBC)
      transfusion were administered. Soon after a second transfusion 5 days later, the
      haemoglobin level fell below pretransfusion levels, together with
      reticulocytopenia, and haematuria-the so-called hyperhaemolysis syndrome
      requiring intensive care and treatment with intravenous immunoglobulins and
      corticosteroids, with resolution of the complication. We want to emphasise the
      importance of suspecting this rare, though severe complication that can appear
      after any RBC transfusion especially in patients with SCD, as the clinical
      syndrome can simulate other more common complications of these patients and a
      further transfusion is contraindicated. There is no standardised treatment, but
      intravenous immunoglobulin and corticosteroids are usually effective.

PMID- 29588282
TI  - Brucellosis accompanied by haemophagocytic lymphohistiocytosis and multiple
      splenic abscesses in a patient with depression.
AB  - A 39-year-old woman was being treated for depression in our clinic. She
      subsequently developed a fever and was diagnosed with pancytopenia and moderate
      splenomegaly. Laboratory and bone marrow results, including markedly increased
      serum ferritin levels, suggested haemophagocytic lymphohistiocytosis. CT showed
      multiple splenic abscesses and ovarian vein thrombosis. All laboratory values
      returned to normal after treatment for culture-positive brucellosis.

PMID- 29588283
TI  - Government must get serious about prevention.

PMID- 29588284
TI  - Southern Health is fined L2m over deaths of two patients.

PMID- 29588285
TI  - CLPP deficiency protects against metabolic syndrome but hinders adaptive
      thermogenesis.
AB  - Mitochondria are fundamental for cellular metabolism as they are both a source
      and a target of nutrient intermediates originating from converging metabolic
      pathways, and their role in the regulation of systemic metabolism is increasingly
      recognized. Thus, maintenance of mitochondrial homeostasis is indispensable for a
      functional energy metabolism of the whole organism. Here, we report that loss of
      the mitochondrial matrix protease CLPP results in a lean phenotype with improved
      glucose homeostasis. Whole-body CLPP-deficient mice are protected from diet
      induced obesity and insulin resistance, which was not present in mouse models
      with either liver- or muscle-specific depletion of CLPP However, CLPP ablation
      also leads to a decline in brown adipocytes function leaving mice unable to cope
      with a cold-induced stress due to non-functional adaptive thermogenesis. These
      results demonstrate a critical role for CLPP in different metabolic stress
      conditions such as high-fat diet feeding and cold exposure providing tools to
      understand pathologies with deregulated Clpp expression and novel insights into
      therapeutic approaches against metabolic dysfunctions linked to mitochondrial
      diseases.

PMID- 29588286
TI  - Circulating Sphingolipids, Insulin, HOMA-IR, and HOMA-B: The Strong Heart Family
      Study.
AB  - Experimental studies suggest ceramides may play a role in insulin resistance.
      However, the relationships of circulating ceramides and related sphingolipids
      with plasma insulin have been underexplored in humans. We measured 15 ceramide
      and sphingomyelin species in fasting baseline samples from the Strong Heart
      Family Study (SHFS), a prospective cohort of American Indians. We examined
      sphingolipid associations with both baseline and follow-up measures of plasma
      insulin, HOMA of insulin resistance (HOMA-IR), and HOMA of beta-cell function
      (HOMA-B) after adjustment for risk factors. Among the 2,086 participants without
      diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0 (16
      carbons, 0 double bond), 18:0, 20:0, or 22:0 were associated with higher plasma
      insulin and higher HOMA-IR at baseline and at follow-up an average of 5.4 years
      later. For example, a twofold higher baseline concentration of ceramide 16:0 was
      associated with 14% higher baseline insulin (P < 0.0001). Associations between
      sphingomyelin species carrying 18:0, 20:0, 22:0, or 24:0 and insulin were
      modified by BMI (P < 0.003): higher levels were associated with lower fasting
      insulin, HOMA-IR, and HOMA-B among those with normal BMI. Our study suggests
      lowering circulating ceramides might be a target in prediabetes and targeting
      circulating sphingomyelins should take into account BMI.

PMID- 29588289
TI  - Short term bailouts will not help "perilous state" of NHS funding, MPs warn.

PMID- 29588287
TI  - Fanconi Anemia FANCM/FNCM-1 and FANCD2/FCD-2 Are Required for Maintaining Histone
      Methylation Levels and Interact with the Histone Demethylase LSD1/SPR-5 in
      Caenorhabditis elegans.
AB  - The histone demethylase LSD1 was originally discovered by removing methyl groups
      from di- and monomethylated histone H3 lysine 4 (H3K4me2/1). Several studies
      suggest that LSD1 plays roles in meiosis as well as in the epigenetic regulation
      of fertility given that, in its absence, there is evidence of a progressive
      accumulation of H3K4me2 and increased sterility through generations. In addition
      to the progressive sterility phenotype observed in the mutants, growing evidence
      for the importance of histone methylation in the regulation of DNA damage repair
      has attracted more attention to the field in recent years. However, we are still
      far from understanding the mechanisms by which histone methylation is involved in
      DNA damage repair, and only a few studies have focused on the roles of histone
      demethylases in germline maintenance. Here, we show that the histone demethylase
      LSD1/CeSPR-5 interacts with the Fanconi anemia (FA) protein FANCM/CeFNCM-1 using
      biochemical, cytological, and genetic analyses. LSD1/CeSPR-5 is required for
      replication stress-induced S phase-checkpoint activation, and its absence
      suppresses the embryonic lethality and larval arrest observed in fncm-1 mutants.
      FANCM/CeFNCM-1 relocalizes upon hydroxyurea exposure and colocalizes with
      FANCD2/CeFCD-2 and LSD1/CeSPR-5, suggesting coordination between this histone
      demethylase and FA components to resolve replication stress. Surprisingly, the FA
      pathway is required for H3K4me2 maintenance, regardless of the presence of
      replication stress. Our study reveals a connection between FA and epigenetic
      maintenance and therefore provides new mechanistic insight into the regulation of
      histone methylation in DNA repair.

PMID- 29588290
TI  - Sixty seconds on . . . prostate cancer.

PMID- 29588288
TI  - Linkage Disequilibrium Estimation in Low Coverage High-Throughput Sequencing
      Data.
AB  - High-throughput sequencing methods that multiplex a large number of individuals
      have provided a cost-effective approach for discovering genome-wide genetic
      variation in large populations. These sequencing methods are increasingly being
      utilized in population genetic studies across a diverse range of species. Two
      side-effects of these methods, however, are (1) sequencing errors and (2)
      heterozygous genotypes called as homozygous due to only one allele at a
      particular locus being sequenced, which occurs when the sequencing depth is
      insufficient. Both of these errors have a profound effect on the estimation of
      linkage disequilibrium (LD) and, if not taken into account, lead to inaccurate
      estimates. We developed a new likelihood method, GUS-LD, to estimate pairwise
      linkage disequilibrium using low coverage sequencing data that accounts for
      undercalled heterozygous genotypes and sequencing errors. Our findings show that
      accurate estimates were obtained using GUS-LD, whereas underestimation of LD
      results if no adjustment is made for the errors.

PMID- 29588291
TI  - A new Editor-in-Chief for Development.

PMID- 29588292
TI  - An interview with James Briscoe.
AB  - James Briscoe is a group leader at The Francis Crick Institute in London. His
      lab's research focusses on the developing vertebrate spinal cord, with a
      particular interest in how sonic hedgehog gradients, and the downstream signal
      transduction and transcriptional networks, regulate the development of this
      tissue. In September 2018, James will become the new Editor-in-Chief of
      Development. We met with James to discuss his career and research interests, the
      importance of interdisciplinary thinking in developmental biology, and his views
      on the current state and future opportunities in scientific publishing.

PMID- 29588293
TI  - Associations Between Changes in Depressive Symptoms and Social Support and
      Diabetes Management Among Low-Income, Predominantly Hispanic Patients in Patient
      Centered Care.
AB  - OBJECTIVE: This study examined whether changes in depressive symptoms and social
      support prospectively predicted diabetes management among Hispanic patients with
      probable depression in patient-centered medical homes at safety-net clinics in
      East Los Angeles, CA. RESEARCH DESIGN AND METHODS: Data were collected from 251
      patients enrolled in a randomized clinical trial testing the effectiveness of a
      self-management intervention assisted by a promotora (Hispanic community health
      worker). Cross-lagged analyses examined associations between changes in
      depression symptoms and social support between baseline and 6-month follow-up and
      self-efficacy and adherence to diabetes management at the 6- and 12-month follow
      ups. RESULTS: Changes in depressive symptoms predicted self-efficacy and level of
      adherence at the 6- and 12-month follow-ups. Changes in total social support and
      emotional social support were correlated only with self-efficacy regarding
      diabetes management at 6-month follow-up. CONCLUSIONS: Decline in depressive
      symptoms is a reliable predictor of improvement in self-efficacy and adherence to
      diabetes management. Further studies are recommended to study psychosocial
      mechanisms related to social relationships other than social support that affect
      diabetes management.

PMID- 29588294
TI  - Aggressive pituitary tumours and carcinomas: two sides of the same coin?
AB  - The European Society of Endocrinology (ESE) survey reported on the largest cohort
      of 125 aggressive pituitary tumours (APT) and 40 pituitary carcinomas (PC).
      Whilst the survey focused on treatment effectiveness, all pathological data were
      not explored in detail. Here, we comment on some interesting pathological
      findings, notably the difference between APT and PC.

PMID- 29588295
TI  - Early-onset neonatal infections in Australia and New Zealand, 2002-2012.
AB  - BACKGROUND: The epidemiology of early-onset neonatal sepsis (EONS) varies over
      time, and requires regular surveillance. OBJECTIVE: To analyse data on EONS in
      Australia and New Zealand. METHODS: Retrospective analysis of data collected
      longitudinally from multiple neonatal units from 2002 to 2012. RESULTS: Of 386
      423 live births, 454 infants had EONS. The incidence rate of EONS was 1.20 per
      1000 live births in 2002 and 0.83 in 2012, decreasing by 4% per year (95% CI 1%
      to 7%, p=0.007). Group B streptococcus (GBS) (37%) and Escherichia coli (25%)
      were the most prevalent organisms. The early-onset GBS (EOGBS) incidence rate was
      0.43/1000 live births, with no evidence of change over time (p=0.3). Of EOGBS
      infected babies, 62% were born at term compared with 8% with early-onset E. coli
      sepsis, p<0.0001. The mortality of E. coli early-onset sepsis (EOS) (25%) was
      higher than GBS (11%), but this difference in mortality was no longer significant
      after adjusting for gestation and birth weight. Mortality from EOS fell
      significantly over the study period (17% per year, 95% CI 10 to 24, p<0.0001).
      CONCLUSIONS: GBS was the most common cause of early sepsis, but the incidence was
      lower than prior to the introduction of intrapartum antibiotic prophylaxis, and
      remained steady over time. The mortality of early-onset E. coli sepsis was
      significantly higher than GBS sepsis, but this may have been because almost all
      babies with E. coli were born preterm, rather than a difference in virulence.

PMID- 29588297
TI  - Intrathecal spinal abscesses due to Candida albicans in an immunocompetent man.
AB  - Infections of the central nervous system due to Candida albicans are uncommon and
      are usually only observed in special circumstances, such as following
      neurosurgery or penetrating head trauma, in immunosuppressed patients, premature
      infants or in patients with ventriculoperitoneal shunts. The author reports a
      case of an immunocompetent man who presented with a thoracic intraspinal abscess
      due to C. albicans Despite surgical drainage and 6 weeks of high-dose fluconazole
      therapy, the abscess extended and recurred in the cervical spine, requiring a
      second operation to arrest the infection.

PMID- 29588298
TI  - Severe immune thrombocytopaenia in a patient taking benznidazole for chronic
      Chagas disease.
AB  - Chagas disease is a parasitic disease that mostly affects Latin American
      countries, but it has currently become a worldwide epidemic due to migration.
      Both drugs marketed for its treatment (benznidazole and nifurtimox) are
      associated with a high rate of adverse reactions. Benznidazole is preferred
      initially because of its more favourable toxicity profile and perceived greater
      efficacy. Hypersensitivity dermatological reactions, gastrointestinal and
      neurological disturbances represent the most common drug-related adverse events.
      General symptoms such as fever, arthralgia, myalgia or bone marrow depression
      (leucopaenia) are seen less frequently. We describe the case of a 33-year-old
      woman with chronic Chagas disease who presented with acute gingival bleeding and
      severe thrombocytopaenia, probably related to benznidazole treatment. Temporal
      association with drug initiation and recovery after treatment withdrawal were
      demonstrated. Clinicians should be aware of the possible association between
      immune thrombocytopaenia and benznidazole, even though the pathogenesis remains
      unclear at present.

PMID- 29588299
TI  - Streptococcus pyogenes primary peritonitis.
AB  - Streptococcus pyogenes, a Gram-positive bacterium, is a rare cause of primary
      peritonitis. Diagnosed on imaging and with positive growth in blood cultures, a
      case of primary peritonitis caused by S. pyogenes is discussed here, with a brief
      literature review, and used to discuss several key principles of antibiotic use,
      including selection of antibiotic, investigations and non-pharmacological
      management of infection.

PMID- 29588300
TI  - Episodes of extreme lower leg pain caused by intraosseous varicose veins.
AB  - We present a case of a 67-year-old man with episodes of extreme pain of the right
      lower extremity that prevented him from walking and sleeping. The patient had a
      history of varices in both legs. Physical examination showed a pretibial varix of
      the right leg inferiorly from a painful spot. X-ray of the right lower leg showed
      a cortex disruption at this spot. MRIs confirmed the disruption of the cortex of
      the right tibia and demonstrated an intraosseous vessel. The diagnosis
      intraosseous varices was made and the vein was surgically resected. Follow-up
      took place after 3 years and the patient was free from any symptoms related to
      the intraosseous varicose vein. The pathophysiology causing the pain symptoms is
      hard to understand, partly due to the limited cases presented with such
      anomalies. We demonstrate our case in the hope to generate more knowledge about
      this disorder.

PMID- 29588296
TI  - Estimating neonatal length of stay for babies born very preterm.
AB  - OBJECTIVE: To predict length of stay in neonatal care for all admissions of very
      preterm singleton babies. SETTING: All neonatal units in England. PATIENTS:
      Singleton babies born at 24-31 weeks gestational age from 2011 to 2014. Data were
      extracted from the National Neonatal Research Database. METHODS: Competing risks
      methods were used to investigate the competing outcomes of death in neonatal care
      or discharge from the neonatal unit. The occurrence of one event prevents the
      other from occurring. This approach can be used to estimate the percentage of
      babies alive, or who have been discharged, over time. RESULTS: A total of 20 571
      very preterm babies were included. In the competing risks model, gestational age
      was adjusted for as a time-varying covariate, allowing the difference between
      weeks of gestational age to vary over time. The predicted percentage of death or
      discharge from the neonatal unit were estimated and presented graphically by week
      of gestational age. From these percentages, estimates of length of stay are
      provided as the number of days following birth and corrected gestational age at
      discharge. CONCLUSIONS: These results can be used in the counselling of parents
      about length of stay and the risk of mortality.

PMID- 29588301
TI  - Leiomyosarcoma: a rare sinonasal malignancy.
AB  - Leiomyosarcomas (LMS) are rare sinonasal malignant tumours with 20 cases of nasal
      LMS previously reported in the literature. An 81-year-old man presented with an
      incidental left nasal lesion associated with left nasal obstruction and
      occasional left-sided blood-stained rhinorrhoea. Nasendoscopic examination showed
      green coloured polyps filling the left nasal cavity with biopsies showing LMS. CT
      imaging did not show any bony erosion. No metastases were found on positron
      emission tomography imaging. The patient underwent endoscopic resection and all
      surgical margins were clear of disease. The patient was declined postoperative
      radiotherapy, and serial follow-up has not shown any recurrence to date. Nasal
      LMS are rare sinonasal smooth muscle tumours and symptoms and radiological
      findings are often non-specific. Therefore, diagnosis is made on
      histopathological and immunohistochemical analysis. Due to their invasive nature,
      the treatment of choice is complete surgical resection, with adjuvant therapy
      reserved for patients with locally advanced or metastatic disease.

PMID- 29588302
TI  - Therapeutic plasma exchange for severe hyperlipidaemia in a patient with poorly
      controlled diabetes.

PMID- 29588303
TI  - Alveolar rhabdomyosarcoma presenting as a lung mass: an uncommon presentation of
      a less common tumor.

PMID- 29588305
TI  - Appendicitis before Age 20 Years Is Associated with an Increased Risk of Later
      Prostate Cancer.
AB  - Background: Appendicitis before age 20 years has been observed to influence the
      risk of several inflammatory conditions, possibly through underlying
      immunological mechanisms. Inflammation has further been suggested to be involved
      in prostate cancer development. We therefore hypothesized that immunological
      characteristics signaled by appendicitis before late adolescence might influence
      the risk of later prostate cancer, and aimed to evaluate this association in a
      population-based study.Methods: We identified a large cohort of Swedish men who
      underwent assessment for military conscription around the age of 18 years (n =
      242,573). Medical diagnoses at time of conscription were available through the
      Swedish Military Conscription Register. The Swedish Cancer Register was used to
      identify diagnoses of prostate cancer. Multivariable adjusted Cox regression
      analyses were used to estimate HR and 95% confidence intervals (95% CIs) for the
      association between appendicitis and prostate cancer.Results: During a median of
      36.7 years of follow-up, 1,684 diagnoses of prostate cancer occurred. We found a
      statistically significant association between appendicitis and overall prostate
      cancer (adjusted HR 1.70; 95% CI, 1.08-2.67). The risk was notably increased for
      advanced (HR 4.42; 95% CI, 1.74-11.22) and lethal (HR 8.95; 95% CI, 2.98-26.91)
      prostate cancer.Conclusions: These results suggest that a diagnosis of
      appendicitis before adulthood potentially signals underlying immune
      characteristics and a pattern of inflammatory response relevant to prostate
      cancer risk.Impact: The study lends support to the proposed role of inflammation
      in prostate carcinogenesis, and adds another area of investigation potentially
      relevant to prostate cancer development. Cancer Epidemiol Biomarkers Prev; 27(6);
      660-4. (c)2018 AACR.

PMID- 29588304
TI  - Inhibitory mechanisms of very low-dose rivaroxaban in non-ST-elevation myocardial
      infarction.
AB  - Very low-dose (VLD) factor Xa (FXa) inhibition, in combination with
      acetylsalicylic acid (ASA) and clopidogrel, is associated with improved outcomes
      in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk
      profile. To date, there are no data documenting platelet inhibition and the
      anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual
      antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation
      myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or
      ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study.
      Coagulation- and platelet-dependent thrombin generation (TG), measured by means
      of the calibrated automated thrombogram, were significantly decreased after in
      vitro and in vivo addition of rivaroxaban. As shown by a total thrombus-formation
      analysis approach, rivaroxaban treatment led to a significantly decreased
      coagulation-dependent (AR-chip) thrombus formation in patients treated with ASA
      plus P2Y12 inhibitor (clopidogrel/ticagrelor), whereas the pure platelet
      dependent (PL-chip) thrombus formation was not affected at all. Adjunctive
      rivaroxaban therapy was not associated with significant differences in platelet
      aggregation assessed by light-transmission aggregometry (LTA). Nevertheless,
      according to fluorescence-activated cell sorter analysis, VLD rivaroxaban
      treatment resulted in a significantly reduced expression of platelet HMGB-1,
      whereas P-selectin exposure was not affected. Furthermore, an enhanced effect of
      rivaroxaban on total thrombus formation and TG was observed in particular in
      clopidogrel nonresponder patients defined as adenosine 5'-diphosphate-induced LTA
      >=40%. VLD rivaroxaban reduces thrombus formation and platelet-dependent TG in
      patients with ACS receiving DAPT, which can be of potential ischemic benefit.
      This trial was registered at www.clinicaltrials.gov as #NCT01417884.

PMID- 29588306
TI  - Hepatitis C Virus Screening Trends: Serial Cross-Sectional Analysis of the
      National Health Interview Survey Population, 2013-2015.
AB  - Background: Rates of hepatitis C virus (HCV) infection are markedly higher for
      baby boomers compared with other birth cohorts, and they are now recommended for
      universal one-time screening. This study examines HCV screening rates and
      predictors for four birth cohorts [born <1945, born 1945-1965 (baby boomers),
      born 1966-1985, and born >1985] of a nationally representative sample over
      time.Methods: We used data from the 2013-2015 National Health Interview Surveys,
      an annual weighted survey of the U.S. civilian noninstitutionalized population.
      We assessed HCV screening prevalence stratified birth cohort with bivariate and
      multivariable logistic regression analyses.Results: There were 15,100
      participants born <1945, 28,725 baby boomers, 28,089 born 1966-1985, and 13,296
      born >1985 in the final analytic sample. Screening was 11.5%-12.8% for baby
      boomers. The second youngest birth cohort was similar to baby boomers (13.7%
      14.9%), whereas the older birth cohort was screened less. After excluding
      participants who typically have higher rates of HCV screening than the general
      population, we developed a multivariable model of the general population. In the
      final model for baby boomers the odds of HCV screening increased significantly
      with each subsequent year (OR=1.20; 95% CI=1.05-1.38 and OR=1.31; 95% CI=1.13
      1.52). HCV screening was also significantly associated with age, gender, and
      race/ethnicity in baby boomers.Conclusions: While HCV screening is increasing
      over time, these increases are minimal and there is substantial room for
      improvement.Impact: Future research should develop interventions to increase HCV
      screening with special focus on groups demonstrating significantly lower
      screening rates, such as Hispanics and females. Cancer Epidemiol Biomarkers Prev;
      27(4); 503-13. (c)2018 AACR.

PMID- 29588307
TI  - Comprehensive genomic profiling aids in treatment of a metastatic endometrial
      cancer.
AB  - FGFR-TACC fusions, including FGFR3-TACC3, have been identified as potential
      oncogenic drivers and actionable alterations in a number of different cancer
      types. The clinical relevance of FGFR3-TACC3 fusions in endometrial cancer has
      not yet been described. Formalin-fixed, paraffin-embedded metastatic endometrial
      carcinoma from the spleen and peritoneum were sent for comprehensive genomic
      profiling (CGP) using the FoundationOne platform as part of a prospective tumor
      genomic profiling protocol. We report the identification of an FGFR3-TACC3 fusion
      in a case of metastatic endometrioid endometrial cancer. Other potentially
      actionable alterations detected in this specimen included PIK3CA T1025S and an
      uncharacterized rearrangement involving TSC2 The patient initially received an
      FGFR inhibitor as an investigational agent and experienced stable disease with
      complete resolution of a pelvic nodule; however, treatment had to be discontinued
      because of intolerable side effects. A PET/CT scan nearly 3 mo after
      discontinuation showed disease progression. She subsequently received the mTOR
      inhibitor, temsirolimus, later accompanied by letrozole, and achieved stable
      disease. Clinical benefit was attributed to the mTOR inhibitor as tumor stained
      negative for estrogen receptor. Temsirolimus was discontinued after >17 mo
      because of disease progression. FGFR inhibitors may have clinical benefit in the
      treatment of endometrial carcinoma with FGFR3-TACC3 fusions. Additionally,
      clinical benefit from an mTOR inhibitor may reflect a response to targeting the
      alteration in PIK3CA or TSC2 More research is needed to understand the activity
      of FGFR3-TACC3 fusions on tumors and to discover additional therapeutic options
      for endometrial carcinoma patients with this gene fusion.

PMID- 29588308
TI  - Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal
      Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic
      Therapies.
AB  - Purpose: Despite the wide use of antiangiogenic drugs in the clinical setting,
      predictive biomarkers of response to these drugs are still unknown.Experimental
      Design: We applied whole-exome sequencing of matched germline and basal plasma
      cell-free DNA samples (WES-cfDNA) on a RAS/BRAF/PIK3CA wild-type metastatic
      colorectal cancer patient with primary resistance to standard treatment regimens,
      including inhibitors to the VEGF:VEGFR2 pathway. We performed extensive
      functional experiments, including ectopic expression of VEGFR2 mutants in
      different cell lines, kinase and drug sensitivity assays, and cell- and patient
      derived xenografts.Results: WES-cfDNA yielded a 77% concordance rate with tumor
      exome sequencing and enabled the identification of the KDR/VEGFR2 L840F clonal,
      somatic mutation as the cause of therapy refractoriness in our patient. In
      addition, we found that 1% to 3% of samples from cancer sequencing projects
      harbor KDR somatic mutations located in protein residues frequently mutated in
      other cancer-relevant kinases, such as EGFR, ABL1, and ALK. Our in vitro and in
      vivo functional assays confirmed that L840F causes strong resistance to
      antiangiogenic drugs, whereas the KDR hot-spot mutant R1032Q confers sensitivity
      to strong VEGFR2 inhibitors. Moreover, we showed that the D717V, G800D, G800R,
      L840F, G843D, S925F, R1022Q, R1032Q, and S1100F VEGFR2 mutants promote tumor
      growth in mice.Conclusions: Our study supports WES-cfDNA as a powerful platform
      for portraying the somatic mutation landscape of cancer and discovery of new
      resistance mechanisms to cancer therapies. Importantly, we discovered that VEGFR2
      is somatically mutated across tumor types and that VEGFR2 mutants can be
      oncogenic and control sensitivity/resistance to antiangiogenic drugs. Clin Cancer
      Res; 24(15); 3550-9. (c)2018 AACR.

PMID- 29588309
TI  - Utility of multimodality cardiac imaging in disorders of the pericardium.
AB  - Disorders of the pericardium represent a diverse range of conditions that
      traditionally may not have received the same level of attention by cardiologists
      and physicians, owing partly to a lack of research into advanced diagnostic
      modalities, and limited, evidence-based treatment options. In recent years, there
      has been a timely resurgence of interest in pericardial diseases, in particular
      pericarditis. This is attributable to advances in multi-modality cardiovascular
      imaging, in particular cardiac magnetic resonance (CMR), which may help guide
      treatment decisions for patients with pericardial syndromes. Additionally,
      increased research and understanding of the pathophysiological basis of
      pericarditis have shed light on the role of inflammation in pericarditis. This
      knowledge may help identify potential specific treatment targets. This article
      aims to provide a practical review of the role of multimodality cardiovascular
      imaging (echocardiography, multidetector cardiac computed tomography (MDCT), CMR)
      in pericardial conditions, focusing on the strengths and potential limitations of
      each imaging modality.

PMID- 29588310
TI  - Echocardiographic approach to catheter closure of atrial septal defects: patient
      selection, procedural guidance and post-procedural checks.
AB  - Echocardiography is the imaging modality of choice to diagnose different types of
      atrial septal defect and to determine which defects are suitable for catheter
      occlusion. In addition to assessment of defect size and rims, transoesophageal
      echocardiography may be used to guide the procedure itself including device
      placement, procedural complications and post-procedural checks. This review
      covers a practical approach to this subject and is accompanied by online videos
      illustrating the technique.

PMID- 29588311
TI  - Risk of Stroke or Death Is Associated With the Timing of Carotid Artery Stenting
      for Symptomatic Carotid Stenosis: A Secondary Data Analysis of the German
      Statutory Quality Assurance Database.
AB  - BACKGROUND: Subgroup analyses from randomized trials indicate that the time
      interval between the neurologic index event and carotid artery stenting is
      associated with periprocedural stroke and death rates in patients with
      symptomatic carotid stenosis. The aim of this article is to analyze whether this
      observation holds true under routine conditions in Germany. METHODS AND RESULTS:
      Secondary data analysis was done on 4717 elective carotid artery stenting
      procedures that were performed for symptomatic carotid stenosis. The patient
      cohort was divided into 4 groups according to the time interval between the index
      event and intervention (group I 0-2, II 3-7, III 8-14, and IV 15-180 days).
      Primary outcome was any in-hospital stroke or death. For risk-adjusted analyses,
      a multilevel multivariable regression model was used. The in-hospital stroke or
      death rate was 3.7% in total and 6.0%, 4.4%, 2.4%, and 3.0% in groups I, II, III,
      and IV, respectively. Adjusted analysis showed a decreased risk for any stroke or
      death in group III, a decreased risk for any major stroke or death in groups III
      and IV, and a decreased risk for any death in groups II and III compared to the
      reference group I. CONCLUSIONS: A short time interval between the neurologic
      index event and carotid artery stenting of up to 7 days is associated with an
      increased risk for stroke or death under routine conditions in Germany. Although
      results cannot prove causal relationships, carotid artery stenting may be
      accompanied by an increased risk of stroke or death during the early period after
      the index event.

PMID- 29588312
TI  - Clustered Emergency Room Visits Following an Acute Heart Failure Admission: A
      Population-Based Study.
AB  - BACKGROUND: While it is well known that heart failure patients presenting to the
      emergency room (ER) have high short-term mortality after discharge, the outcomes
      of patients with heart failure with repeated ER visits within a short time are
      not known. In this study, we aimed to determine whether clustering is associated
      with an increased risk of death. METHODS AND RESULTS: This is a retrospective,
      population-based cohort study with an accrual window between 2003 and 2014 and
      maximal follow-up up to and including March 31, 2015. Data were obtained from
      administrative databases from Ontario, Canada. Clustering was defined a priori as
      3 or more ER visits within a 6-month period. The main outcome of interest was
      time to death conditional on 6-month survival. A total of 72 810 patients with an
      index hospitalization for acute heart failure were evaluated. ER clustering was
      observed in 15.1% of the population. Increased burden of comorbidities, primary
      rural residence, and lack of primary care provider were identified as factors
      associated with ER clustering. Age- and sex-adjusted mortality for clustered
      patients was higher than for nonclustered (hazard ratio [HR] 1.51; 95% confidence
      interval, 1.47-1.55, P<0.0001). Adjusted mortality risk was also higher for
      patients with clustered ER visits (HR 1.42; 95% confidence interval 1.38-1.46;
      P<0.0001). CONCLUSIONS: Clustering, as defined by 3 or more ER visits for any
      reason within 6 months of index heart failure hospitalization reflects a novel
      risk factor associated with increased mortality. Future research into the
      strategies to better manage complex patients with heart failure with recurrent ER
      visits are warranted.

PMID- 29588313
TI  - Reliability and Physiological Interpretation of Pulmonary Gas Exchange by
      "Circulatory Equivalents" in Chronic Heart Failure.
AB  - BACKGROUND: Peak ratios of pulmonary gas-exchange to ventilation during exercise
      (VO2/VE and VCO2/VE, termed "circulatory equivalents") are sensitive to heart
      failure (HF) severity, likely reflecting low and/or poorly distributed pulmonary
      perfusion. We tested whether peak VO2/VE and VCO2/VE would: (1) distinguish HF
      patients from controls; (2) be independent of incremental exercise protocol; and
      (3) correlate with lactate threshold (LT) and ventilatory compensation point
      (VCP), respectively. METHODS AND RESULTS: Twenty-four HF patients (61+/-11 years)
      with reduced ejection fraction (31+/-8%) and 11 controls (63+/-7 years) performed
      ramp-incremental cycle ergometry. Eighteen HF patients also performed slow (5+/-1
      W/min), medium (9+/-4 W/min), and fast (19+/-6 W/min) ramps. Peak VO2/VE and
      VCO2/VE from X-Y plot, and LT and VCP from 9-panel plot, were determined by 2
      independent, blinded, assessors. Peak VO2/VE (31.2+/-4.4 versus 41.8+/-4.8 mL/L;
      P<0.0001) and VCO2/VE (29.3+/-3.0 versus 36.9+/-4.0 mL/L; P<0.0001) were lower in
      HF than controls. Within individuals, there was no difference across 3 ramp rates
      in peak VO2/VE (P=0.62) or VCO2/VE (P=0.97). Coefficient of variation (CV) in
      peak VO2/VE was lower than for LT (5.1+/-2.1% versus 8.2+/-3.7%; P=0.014), and
      coefficient of variation in peak VCO2/VE was lower than for VCP (3.3+/-1.8%
      versus 8.7+/-4.2%; P<0.001). In all participants, peak VO2/VE was correlated
      with, but occurred earlier than, LT (r2=0.94; mean bias, -0.11 L/min), and peak
      VCO2/VE was correlated with, but occurred earlier than, VCP (r2=0.98; mean bias 
      0.08 L/min). CONCLUSIONS: Peak circulatory equivalents during exercise are
      strongly associated with (but not identical to) LT and VCP. Peak circulatory
      equivalents are reliable, objective, effort-independent indices of gas-exchange
      abnormality in HF.

PMID- 29588314
TI  - Comparison of Time-to-First Event and Recurrent-Event Methods in Randomized
      Clinical Trials.
AB  - BACKGROUND: Most phase-3 trials feature time-to-first event end points for their
      primary and secondary analyses. In chronic diseases, where a clinical event can
      occur >1 time, recurrent-event methods have been proposed to more fully capture
      disease burden and have been assumed to improve statistical precision and power
      compared with conventional time-to-first methods. METHODS: To better characterize
      factors that influence statistical properties of recurrent-event and time-to
      first methods in the evaluation of randomized therapy, we repeatedly simulated
      trials with 1:1 randomization of 4000 patients to active versus control therapy,
      with true patient-level risk reduction of 20% (ie, relative risk=0.80). For
      patients who discontinued active therapy after a first event, we assumed their
      risk reverted subsequently to their original placebo-level risk. Through
      simulation, we varied the degree of between-patient heterogeneity of risk and the
      extent of treatment discontinuation. Findings were compared with those from
      actual randomized clinical trials. RESULTS: As the degree of between-patient
      heterogeneity of risk increased, both time-to-first and recurrent-event methods
      lost statistical power to detect a true risk reduction and confidence intervals
      widened. The recurrent-event analyses continued to estimate the true relative
      risk (0.80) as heterogeneity increased, whereas the Cox model produced attenuated
      estimates. The power of recurrent-event methods declined as the rate of study
      drug discontinuation postevent increased. Recurrent-event methods provided
      greater power than time-to-first methods in scenarios where drug discontinuation
      was <=30% after a first event, lesser power with drug discontinuation rates of
      >=60%, and comparable power otherwise. We confirmed in several actual trials of
      chronic heart failure that treatment effect estimates were attenuated when
      estimated via the Cox model and that increased statistical power from recurrent
      event methods was most pronounced in trials with lower treatment discontinuation
      rates. CONCLUSIONS: We find that the statistical power of both recurrent-events
      and time-to-first methods are reduced by increasing heterogeneity of patient
      risk, a parameter not included in conventional power and sample size formulas.
      Data from real clinical trials are consistent with simulation studies, confirming
      that the greatest statistical gains from use of recurrent-events methods occur in
      the presence of high patient heterogeneity and low rates of study drug
      discontinuation.

PMID- 29588315
TI  - Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis, and
      Atherogenesis.
AB  - BACKGROUND: The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome
      Study) showed that antagonism of interleukin (IL)-1beta reduces coronary heart
      disease in patients with a previous myocardial infarction and evidence of
      systemic inflammation, indicating that pathways required for IL-1beta secretion
      increase cardiovascular risk. IL-1beta and IL-18 are produced via the NLRP3
      inflammasome in myeloid cells in response to cholesterol accumulation, but
      mechanisms linking NLRP3 inflammasome activation to atherogenesis are unclear.
      The cholesterol transporters ATP binding cassette A1 and G1 (ABCA1/G1) mediate
      cholesterol efflux to high-density lipoprotein, and Abca1/g1 deficiency in
      myeloid cells leads to cholesterol accumulation. METHODS: To interrogate
      mechanisms connecting inflammasome activation with atherogenesis, we used mice
      with myeloid Abca1/g1 deficiency and concomitant deficiency of the inflammasome
      components Nlrp3 or Caspase-1/11. Bone marrow from these mice was transplanted
      into Ldlr-/- recipients, which were fed a Western-type diet. RESULTS: Myeloid
      Abca1/g1 deficiency increased plasma IL-18 levels in Ldlr-/- mice and induced IL
      1beta and IL-18 secretion in splenocytes, which was reversed by Nlrp3 or Caspase
      1/11 deficiency, indicating activation of the NLRP3 inflammasome. Nlrp3 or
      Caspase-1/11 deficiency decreased atherosclerotic lesion size in myeloid Abca1/g1
      deficient Ldlr-/- mice. Myeloid Abca1/g1 deficiency enhanced caspase-1 cleavage
      not only in splenic monocytes and macrophages, but also in neutrophils, and
      dramatically enhanced neutrophil accumulation and neutrophil extracellular trap
      formation in atherosclerotic plaques, with reversal by Nlrp3 or Caspase-1/11
      deficiency, suggesting that inflammasome activation promotes neutrophil
      recruitment and neutrophil extracellular trap formation in atherosclerotic
      plaques. These effects appeared to be indirectly mediated by systemic
      inflammation leading to activation and accumulation of neutrophils in plaques.
      Myeloid Abca1/g1 deficiency also activated the noncanonical inflammasome, causing
      increased susceptibility to lipopolysaccharide-induced mortality. Patients with
      Tangier disease, who carry loss-of-function mutations in ABCA1 and have increased
      myeloid cholesterol content, showed a marked increase in plasma IL-1beta and IL
      18 levels. CONCLUSIONS: Cholesterol accumulation in myeloid cells activates the
      NLRP3 inflammasome, which enhances neutrophil accumulation and neutrophil
      extracellular trap formation in atherosclerotic plaques. Patients with Tangier
      disease, who have increased myeloid cholesterol content, showed markers of
      inflammasome activation, suggesting human relevance.

PMID- 29588317
TI  - Spatiotemporal Multi-omics Mapping Generates a Molecular Atlas of the Aortic
      Valve and Reveals Networks Driving Disease.
AB  - Background -No pharmacological therapy exists for calcific aortic valve disease
      (CAVD), which confers a dismal prognosis without invasive valve replacement. The
      search for therapeutics and early diagnostics is challenging since CAVD presents
      in multiple pathological stages. Moreover, it occurs in the context of a complex,
      multi-layered tissue architecture, a rich and abundant extracellular matrix
      phenotype, and a unique, highly plastic and multipotent resident cell population.
      Methods -A total of 25 human stenotic aortic valves obtained from valve
      replacement surgeries were analyzed by multiple modalities, including
      transcriptomics and global unlabeled and label-based tandem-mass-tagged
      proteomics. Segmentation of valves into disease-stage-specific samples was guided
      by near infrared molecular imaging, and anatomical layer-specificity was
      facilitated by laser capture microdissection. Side-specific cell cultures were
      subjected to multiple calcifying stimuli, and their calcification potential and
      basal/stimulated proteomes were evaluated. Molecular (protein-protein)
      interaction networks were built and their central proteins and disease
      associations were identified. Results -Global transcriptional and protein
      expression signatures differed between the non-diseased, fibrotic, and calcific
      stages of CAVD. Anatomical aortic valve microlayers exhibited unique proteome
      profiles that were maintained throughout disease progression and identified glial
      fibrillary acidic protein (GFAP) as a specific marker of valvular interstitial
      cells (VICs) from the spongiosa layer. CAVD disease progression was marked by an
      emergence of smooth muscle cell activation, inflammation, and calcification
      related pathways. Proteins overrepresented in the disease-prone fibrosa are
      functionally annotated to fibrosis and calcification pathways, and we found that
      in vitro, fibrosa-derived VICs demonstrated greater calcification potential than
      those from the ventricularis. These studies confirmed that the microlayer
      specific proteome was preserved in cultured VICs, and that VICs exposed to ALPL
      dependent and ALPL-independent calcifying stimuli had distinct proteome profiles,
      both of which overlapped with that of the whole tissue. Analysis of protein
      protein interaction networks found a significant closeness to multiple
      inflammatory and fibrotic diseases. Conclusions -A spatially- and temporally
      resolved multi-omics, and network and systems biology strategy identifies the
      first molecular regulatory networks in CAVD, a cardiac condition without a
      pharmacological cure, and describes a novel means of systematic disease ontology
      that is broadly applicable to comprehensive omics studies of cardiovascular
      diseases.

PMID- 29588316
TI  - Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II
      Molecule-Restricted Peptide Epitopes of Apolipoprotein B.
AB  - BACKGROUND: CD4+ T cells play an important role in atherosclerosis, but their
      antigen specificity is poorly understood. Immunization with apolipoprotein B
      (ApoB, core protein of low density lipoprotein) is known to be atheroprotective
      in animal models. Here, we report on a human APOB peptide, p18, that is sequence
      identical in mouse ApoB and binds to both mouse and human major
      histocompatibility complex class II molecules. METHODS: We constructed p18
      tetramers to detect human and mouse APOB-specific T cells and assayed their
      phenotype by flow cytometry including CD4 lineage transcription factors,
      intracellular cytokines, and T cell receptor activation. Apolipoprotein E
      deficient ( Apoe-/-) mice were vaccinated with p18 peptide or adjuvants alone,
      and atherosclerotic burden in the aorta was determined. RESULTS: In human
      peripheral blood mononuclear cells from donors without cardiovascular disease,
      p18 specific CD4+ T cells detected by a new human leukocyte antigen-antigen D
      related-p18 tetramers were mostly Foxp3+ regulatory T cells (Tregs). Donors with
      subclinical cardiovascular disease as detected by carotid artery ultrasound had
      Tregs coexpressing retinoic acid-related orphan receptor gamma t or T-bet, which
      were both almost absent in donors without cardiovascular disease. In Apoe-/-
      mice, immunization with p18 induced Tregs and reduced atherosclerotic lesions.
      After peptide restimulation, responding CD4+ T cells identified by Nur77-GFP
      (green fluorescent protein) were highly enriched in Tregs. A new mouse I-Ab-p18
      tetramer identified the expansion of p18-specific CD4+ T cells on vaccination,
      which were enriched for interleukin-10-producing Tregs. CONCLUSIONS: These
      findings show that APOB p18-specific CD4+ T cells are mainly Tregs in healthy
      donors, but coexpress other CD4 lineage transcription factors in donors with
      subclinical cardiovascular disease. This study identifies ApoB peptide 18 as the
      first Treg epitope in human and mouse atherosclerosis.

PMID- 29588318
TI  - Rapid Construction of Antitumor T-cell Receptor Vectors from Frozen Tumors for
      Engineered T-cell Therapy.
AB  - T cells genetically engineered with tumor antigen-specific T-cell receptor (TCR)
      genes have demonstrated therapeutic potential in patients with solid tumors. In
      order to achieve broader application, an efficient method to identify TCR genes
      for an array of tumor antigens and HLA restriction elements is required. Here, we
      have developed a method to construct a TCR-expression library from specimens,
      including frozen tumor biopsies, that contain antigen-specific T cells. TCR
      expressing cassettes were constructed and cloned in a retroviral plasmid vector
      within 24 hours by unbiased PCR amplification of TCR alpha and beta chain
      variable regions assembled with TCR constant regions. The method was validated by
      constructing TCR-expressing vectors from tumor antigen-specific T-cell clones and
      functionally assessing TCR gene-transduced T cells. We applied this method to
      frozen ovarian tumor specimens that were infiltrated by tumor antigen-specific T
      cells. The tumor-derived TCR libraries were expressed in peripheral T cells from
      healthy volunteers and screened for tumor antigen-specific TCR pairs with the use
      of an MHC/peptide tetramer reagent. Tumor antigen-specific TCR-expressing
      transgenes were recovered from isolated tetramer-positive T cells. Peripheral T
      cells that were engineered with library-derived TCR gene showed potent
      therapeutic antitumor effect in a tumor xenograft model. Our method can
      efficiently and rapidly provide tumor-specific TCR-expressing viral vectors for
      the manufacture of therapeutic and personalized antitumor T-cell products. Cancer
      Immunol Res; 6(5); 594-604. (c)2018 AACR.

PMID- 29588319
TI  - Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven
      Production of a Bispecific T-cell Engager.
AB  - T cells expressing chimeric antigen receptors (CART) have shown significant
      promise in clinical trials to treat hematologic malignancies, but their efficacy
      in solid tumors has been limited. Oncolytic viruses have the potential to act in
      synergy with immunotherapies due to their immunogenic oncolytic properties and
      the opportunity of incorporating therapeutic transgenes in their genomes. Here,
      we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting,
      bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell
      therapy in solid tumors. We report that CART cells targeting the folate receptor
      alpha (FR-alpha) successfully infiltrated preestablished xenograft tumors but
      failed to induce complete responses, presumably due to the presence of antigen
      negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis
      significantly improved CART-cell activation and proliferation, while increasing
      cytokine production and cytotoxicity, and showed an in vitro favorable safety
      profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells
      redirected CART cells toward EGFR in the absence of FR-alpha, thereby addressing
      tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T
      cells found in CART-cell preparations toward tumor cells. The combinatorial
      approach improved antitumor efficacy and prolonged survival in mouse models of
      cancer when compared with the monotherapies, and this was the result of an
      increased BiTE-mediated T-cell activation in tumors. Overall, these results
      demonstrated that the combination of a BiTE-expressing oncolytic virus with
      adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as
      monotherapies in solid tumors and encourage its further evaluation in human
      trials. Cancer Immunol Res; 6(5); 605-16. (c)2018 AACR.

PMID- 29588320
TI  - Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness.
AB  - Regulatory T cells (Treg) have long been considered one-sided suppressors of
      antitumor immune responses and hence associated with poor patient outcome in
      cancer. However, evidence is mounting of a paradoxical positive prognostic effect
      of Tregs on certain malignancies, including urinary bladder cancer (UBC). This
      discrepancy has partly been attributed to the shear misidentification of Tregs,
      but also to the inflammatory profile of the tumor. Our aim was to determine
      whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg
      phenotype and to investigate putative beneficial Treg functions, focusing on
      tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected
      UBC were prospectively included. We show, by using a broad range of analytical
      approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically,
      functionally, and epigenetically represent a true Treg population. At the
      invasive front of UBC tumors, we found an inverse relationship between Treg
      frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive
      factor induced by tumor-promoting inflammation. Correspondingly, a significant,
      dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression
      was observed in both macrophages and UBC cells. Also, we found that Treg
      frequency specifically at the invasive front positively correlated with survival.
      Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment
      as a mechanism explaining the paradoxical positive prognostic impact of tumor
      infiltrating Tregs in UBC. Cancer Immunol Res; 6(5); 528-38. (c)2018 AACR.

PMID- 29588321
TI  - Protumor Steering of Cancer Inflammation by p50 NF-kappaB Enhances Colorectal
      Cancer Progression.
AB  - Although tumor-associated macrophages (TAM) display a M2-skewed tumor-promoting
      phenotype in most cancers, in colorectal cancer, both TAM polarization and its
      impact remain controversial. We investigated the role of the M2-polarizing p50 NF
      kappaB subunit in orchestrating TAM phenotype, tumor microenvironment
      composition, and colorectal cancer progression. We first demonstrated, by
      parallel studies in colitis-associated cancer (CAC) and in genetically driven
      ApcMin mouse models, that the p50-dependent inhibition of M1-polarized gut
      inflammation supported colorectal cancer development. In accordance with these
      studies, p50-/- mice displayed exacerbated CAC with fewer and smaller tumors,
      along with enhanced levels of M1/Th1 cytokines/chemokines, including IL12 and
      CXCL10, whose administration restrained CAC development in vivo The inflammatory
      profile supporting tumor resistance in colons from p50-/- tumor bearers
      correlated inversely with TAM load and positively with both recruitment of NK,
      NKT, CD8+ T cells and number of apoptotic tumor cells. In agreement, myeloid
      specific ablation of p50 promoted tumor resistance in mice, whereas in colorectal
      cancer patients, a high number of p50+ TAMs at the invasive margin was associated
      with decreased IL12A and TBX21 expression and worse postsurgical outcome. Our
      findings point to p50 involvement in colorectal cancer development, through its
      engagement in the protumor activation of macrophages, and identify a candidate
      for prognostic and target therapeutic intervention. Cancer Immunol Res; 6(5); 578
      93. (c)2018 AACR.

PMID- 29588322
TI  - GMC calls for law change to make doctors' reflections legally protected.

PMID- 29588323
TI  - Interagency collaboration models for people with mental ill health in contact
      with the police: a systematic scoping review.
AB  - OBJECTIVE: To identify existing evidence on interagency collaboration between law
      enforcement, emergency services, statutory services and third sector agencies
      regarding people with mental ill health. DESIGN: Systematic scoping review.
      Scoping reviews map particular research areas to identify research gaps. DATA
      SOURCES AND ELIGIBILITY: ASSIA, CENTRAL, the Cochrane Library databases, Criminal
      Justice Abstracts, ERIC, Embase, MEDLINE, PsycINFO, PROSPERO and Social Care
      Online and Social Sciences Citation Index were searched up to 2017, as were grey
      literature and hand searches. Eligible articles were empirical evaluations or
      descriptions of models of interagency collaboration between the police and other
      agencies. STUDY APPRAISAL AND SYNTHESIS: Screening and data extraction were
      undertaken independently by two researchers. Arksey's framework was used to
      collate and map included studies. RESULTS: One hundred and twenty-five studies
      were included. The majority of articles were of descriptions of models (28%),
      mixed methods evaluations of models (18%) and single service evaluations (14%).
      The most frequently reported outcomes (52%) were 'organisational or service level
      outcomes' (eg, arrest rates). Most articles (53%) focused on adults with mental
      ill health, whereas others focused on adult offenders with mental ill health
      (17.4%). Thirteen models of interagency collaboration were described, each
      involving between 2 and 13 agencies. Frequently reported models were 'prearrest
      diversion' of people with mental ill health (34%), 'coresponse' involving joint
      response by police officers paired with mental health professionals (28.6%) and
      'jail diversion' following arrest (23.8%). CONCLUSIONS: We identified 13
      different interagency collaboration models catering for a range of mental health
      related interactions. All but one of these models involved the police and mental
      health services or professionals. Several models have sufficient literature to
      warrant full systematic reviews of their effectiveness, whereas others need
      robust evaluation, by randomised controlled trial where appropriate. Future
      evaluations should focus on health-related outcomes and the impact on key
      stakeholders.

PMID- 29588324
TI  - Wisconsin microbiome study, a cross-sectional investigation of dietary fibre,
      microbiome composition and antibiotic-resistant organisms: rationale and methods.
AB  - INTRODUCTION: Prevention of multidrug-resistant organism (MDRO) infections, such
      as those caused by methicillin-resistant Staphylococcus aureus, vancomycin
      resistant enterococci, fluoroquinolone-resistant Gram-negative bacteria and
      Clostridium difficile is crucial. Evidence suggests that dietary fibre increases
      gut microbial diversity, which may help prevent colonisation and subsequent
      infection by MDROs. The aim of the Winning the War on Antibiotic Resistance
      (WARRIOR) project is to examine associations of dietary fibre consumption with
      the composition of the gut microbiota and gut colonisation by MDROs. The
      secondary purpose of the study is to create a biorepository of multiple body site
      specimens for future microbiota research. METHODS AND ANALYSIS: The WARRIOR
      project collects biological specimens, including nasal, oral and skin swabs and
      saliva and stool samples, along with extensive data on diet and MDRO risk
      factors, as an ancillary study of the Survey of the Health of Wisconsin (SHOW).
      The SHOW is a population-based health survey collecting data on several different
      health determinants and outcomes, as well as objective body measurements and
      biological specimens. WARRIOR participants include 600 randomly selected
      Wisconsin residents age 18 and over. Specimens are screened for MDRO colonisation
      and DNA is extracted for 16S ribosomal RNA-based microbiota sequencing. Data will
      be analysed to assess the relationship between dietary fibre, the gut microbiota
      composition and gut MDRO colonisation. ETHICS AND DISSEMINATION: The WARRIOR
      project is approved by the University of Wisconsin Institutional Review Board.
      The main results of this study will be published in a peer-reviewed scientific
      journal.

PMID- 29588325
TI  - Delineating the trajectories of social and occupational functioning of young
      people attending early intervention mental health services in Australia: a
      longitudinal study.
AB  - OBJECTIVES: Mental disorders typically emerge during adolescence and young
      adulthood and put young people at risk for prolonged socioeconomic difficulties.
      This study describes the longitudinal course of social and occupational
      functioning of young people attending primary care-based, early intervention
      services. DESIGN: A longitudinal study of young people receiving mental
      healthcare. SETTING: Data were collected between January 2005 and August 2017
      from a designated primary care-based mental health service. PARTICIPANTS: 554
      young people (54% women) aged 12-32 years. MEASURES: A systematic medical file
      audit collected clinical and functional information at predetermined time
      intervals (ie, 3 months to 5+ years) using a clinical pro forma. Group-based
      trajectory modelling (GBTM) was used to identify distinct trajectories of social
      and occupational functioning over time (median number of observations per
      person=4; median follow-up time=23 months). RESULTS: Between first clinical
      contact and time last seen, 15% of young people had reliably deteriorated, 23%
      improved and 62% did not demonstrate substantive change in function. Of the whole
      cohort, 69% had functional scores less than 70 at time last seen, indicative of
      ongoing and substantive impairment. GBTM identified six distinct functional
      trajectories whereby over 60% had moderate-to-serious functional impairment at
      entry and remained chronically impaired over time; 7% entered with serious
      impairment and deteriorated further; a quarter were mildly impaired at entry and
      functionally recovered and only a small minority (4%) presented with serious
      impairments and functionally improved over time. Not being in education,
      employment or training, previous hospitalisation and a younger age at baseline
      emerged as significant predictors of these functional trajectories. CONCLUSION:
      Young people with emerging mental disorders have significant functional
      impairment at presentation for care, and for the majority, it persists over the
      course of clinical care. In addition to providing clinical care earlier in the
      course of illness, these data suggest that more sophisticated and more intensive
      individual-level and organisational strategies may be required to achieve
      significant and sustained functional improvements.

PMID- 29588327
TI  - Educational attainment of children born to mothers with epilepsy.
AB  - OBJECTIVE: Small prospective studies have identified that children exposed to
      valproate in utero have poorer scores on cognitive testing. We wanted to identify
      whether children exposed to antiepileptic drugs (AEDs) in utero have poorer
      school performance. METHODS: We used anonymised, linked, routinely collected
      healthcare records to identify children born to mothers with epilepsy. We linked
      these children to their national attainment Key Stage 1 (KS1) tests in
      mathematics, language and science at the age of 7 and compared them with matched
      children born to mothers without epilepsy, and with the national KS1 results. We
      used the core subject indicator (CSI) as an outcome measure (the proportion of
      children achieving a minimum standard in all subjects) and the results in
      individual subjects. RESULTS: We identified 440 children born to mothers with
      epilepsy with available KS1 results. Compared with a matched control group, fewer
      children with mothers being prescribed sodium valproate during pregnancy achieved
      the national minimum standard in CSI (-12.7% less than the control group),
      mathematics (-12.1%), language (-10.4%) and in science (-12.2%). Even fewer
      children with mothers being prescribed multiple AEDs during pregnancy achieved a
      national minimum standard: CSI (by -20.7% less than the control group),
      mathematics (-21.9%), language (-19.3%) and science (-19.4%). We did not observe
      any significant difference in children whose mothers were prescribed
      carbamazepine or were not taking an AED when compared with the control group.
      CONCLUSIONS: In utero exposure to AEDs in combination, or sodium valproate alone,
      is associated with a significant decrease in attainment in national educational
      tests for 7-year-old children compared with both a matched control group and the
      all-Wales national average. These results give further support to the cognitive
      and developmental effects of in utero exposure to sodium valproate as well as
      multiple AEDs, which should be balanced against the need for effective seizure
      control for women during pregnancy.

PMID- 29588328
TI  - AEDs or no AEDs during pregnancy? That is the question.

PMID- 29588326
TI  - Impact of CAre-related Regret Upon Sleep (ICARUS) cohort study: protocol of a 3
      year multicentre, international, prospective cohort study of novice healthcare
      professionals.
AB  - INTRODUCTION: Healthcare professionals are particularly at risk of developing
      numerous physical and psychological health problems. The experiences of emotional
      burden associated with providing healthcare, notably care-related regret, have
      been associated with these health problems, but only using cross-sectional data
      so far. Evidence of a causal impact of regret has not been assessed. The Impact
      of CAre-related Regret Upon Sleep (ICARUS) study is the first prospective and
      international cohort study established to examine how newly practising healthcare
      professionals adapt to their challenging job by assessing the impact of care
      related regret on sleep and job quitting. METHOD AND ANALYSIS: The ICARUS cohort
      study will include newly practising healthcare professionals working in acute
      care hospitals and clinics recruited between May 2017 and November 2019. Data
      collection, which will begin as soon as the participant starts working with
      patients, will consist of a 1-year weekly assessment using a secure web survey.
      Follow-up data will be collected at 6, 12, 18 and 24 months after the end of the
      first year. We will collect detailed information on the experience of care
      related regret (ie, highest regret intensity, accumulation of regrets and coping
      strategies related to regrets), sleep problems and job quitting. Moreover,
      quality of life, health status and burnout will be assessed during the follow-up.
      Several confounders factors, including sociodemographic characteristics,
      personality, night shifts and work environment characteristics, will be assessed.
      ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of
      Geneva Canton, Switzerland (CCER2016-02041), the Ethics Committee of London South
      Bank University (HSCSEP/17/06) and the University Research Ethics Committee of
      Bedfordshire (UREC106). Other study centres deemed local ethical approval
      unnecessary since the main ethics committee (Geneva) had already accepted the
      project. Results will be published in relevant scientific journals and be
      disseminated in international conferences. Fully anonymised data and
      questionnaires will be freely accessible to everyone (scientists and general
      public).

PMID- 29588329
TI  - Social isolation and loneliness as risk factors for myocardial infarction, stroke
      and mortality: UK Biobank cohort study of 479 054 men and women.
AB  - OBJECTIVE: To examine whether social isolation and loneliness (1) predict acute
      myocardial infarction (AMI) and stroke among those with no history of AMI or
      stroke, (2) are related to mortality risk among those with a history of AMI or
      stroke, and (3) the extent to which these associations are explained by known
      risk factors or pre-existing chronic conditions. METHODS: Participants were 479
      054 individuals from the UK Biobank. The exposures were self-reported social
      isolation and loneliness. AMI, stroke and mortality were the outcomes. RESULTS:
      Over 7.1 years, 5731 had first AMI, and 3471 had first stroke. In model adjusted
      for demographics, social isolation was associated with higher risk of AMI (HR
      1.43, 95% CI 1.3 to -1.55) and stroke (HR 1.39, 95% CI 1.25 to 1.54). When
      adjusted for all the other risk factors, the HR for AMI was attenuated by 84% to
      1.07 (95% CI 0.99 to 1.16) and the HR for stroke was attenuated by 83% to 1.06
      (95% CI 0.96 to 1.19). Loneliness was associated with higher risk of AMI before
      (HR 1.49, 95% CI 1.36 to 1.64) but attenuated considerably with adjustments (HR
      1.06, 95% CI 0.96 to 1.17). This was also the case for stroke (HR 1.36, 95% CI
      1.20 to 1.55 before and HR 1.04, 95% CI 0.91 to 1.19 after adjustments). Social
      isolation, but not loneliness, was associated with increased mortality in
      participants with a history of AMI (HR 1.25, 95% CI 1.03 to 1.51) or stroke (HR
      1.32, 95% CI 1.08 to 1.61) in the fully adjusted model. CONCLUSIONS: Isolated and
      lonely persons are at increased risk of AMI and stroke, and, among those with a
      history of AMI or stroke, increased risk of death. Most of this risk was
      explained by conventional risk factors.

PMID- 29588331
TI  - Predictors of prolonged length of hospital stay for infants with bronchiolitis.
AB  - Among inpatients suffering from bronchiolitis, approximately a quarter may
      undergo a prolonged length of stay (LOS) for the treatment of their respiratory
      condition. However, there have been few research studies that have evaluated
      variables that may be associated with a prolonged LOS in these patients,
      especially in low-income and middle-income countries, where the clinical and
      economic burden of the disease is the greatest. In an analytical single-center
      cross-sectional study, we included a population of patients with acute
      bronchiolitis hospitalized between March and June 2016. We collected demographic
      and clinical information and the LOS of each patient. Prolonged LOS for
      bronchiolitis was defined as at least one hospital stay of 5 or more days. A
      total of 303 patients were included, with 176 (58.1%) male and a median (IQR) age
      of 3.0 (1.0-7.0) months. After controlling for gender, history of
      bronchopulmonary dysplasia, number of days with respiratory symptoms, the
      presence of apnea as an initial manifestation of bronchiolitis, and other
      underlying disease conditions, we found that the independent predictors of
      prolonged LOS for bronchiolitis in our study population included age (OR 0.92;
      95% CI 0.84 to 0.99; p=0.049), history of prematurity (OR 6.34; 95% CI 1.10 to
      36.46; p=0.038), respiratory syncytial virus isolation (OR 1.92; 95% CI 1.02 to
      3.73; p=0.048), and initial oxygen saturation (OR 0.94; 95% CI 0.88 to 0.98;
      p=0.048). The factors identified should be taken into account when planning
      policies to reduce the duration of hospital stay in infants with bronchiolitis.

PMID- 29588330
TI  - ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with
      Everolimus in Prostate Cancer.
AB  - Androgen receptor (AR) signaling plays a key role in prostate cancer progression,
      and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen
      for patients with advanced disease. Unfortunately, most prostate cancers
      eventually become androgen-independent and resistant to ADT with patients
      progressing to metastatic castration-resistant prostate cancer (mCRPC).
      Constitutively activated AR variants (AR-V) have emerged as mediators of
      resistance to AR-targeted therapy and the progression of mCRPC, and they
      represent an important therapeutic target. Out of at least 15 AR-Vs described
      thus far, AR-V7 is the most abundant, and its expression correlates with ADT
      resistance. ONC201/TIC10 is the founding member of the imipridone class of small
      molecules and has shown anticancer activity in a broad range of tumor types.
      ONC201 is currently being tested in phase I/II clinical trials for advanced solid
      tumors, including mCRPC, and hematologic malignancies. There has been promising
      activity observed in patients in early clinical testing. This study demonstrates
      preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of
      prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in
      both castration-resistant and -sensitive prostate cancer cells. Furthermore, the
      data demonstrate that ONC201 downregulates the expression of key drivers of
      prostate cancer such as AR-V7 and downstream target genes including the
      clinically used biomarker PSA (KLK3). Finally, the data also provide a
      preclinical rationale for combination of ONC201 with approved therapeutics for
      prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or
      docetaxel.Implications: The preclinical efficacy of ONC201 as a single agent or
      in combination, in hormone-sensitive or castration-resistant prostate cancer,
      suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5);
      754-66. (c)2018 AACR.

PMID- 29588332
TI  - Risks of irritable bowel syndrome in children with infantile urinary tract
      infection: a 13-year nationwide cohort study.
AB  - Early life events play a crucial role in the development of irritable bowel
      syndrome (IBS). Some evidence suggests the phenomenon of cross-organ
      sensitization between bladder and colon. Whether urinary tract infection (UTI)
      during infancy is a risk factor of childhood IBS remains to be elucidated. In
      this retrospective cohort study, we selected 31 788 infants who had UTI between
      2000 and 2011 as a UTI cohort and selected 127 152 infants without UTI as a
      comparison cohort, matched by age, sex and level of urbanization of living area.
      Incidence density and HRs with CIs of IBS between UTI and non-UTI cohorts were
      calculated by the end of 2012. The incidence density of IBS during the study
      period was 1.52-fold higher in the UTI cohort (95% CI 1.38 to 1.67) compared with
      the non-UTI cohort (2.05 vs 1.32 per 10 000 person-years). The HR of IBS was
      slightly higher for boys (1.53; 95% CI 1.34 to 1.73) than for girls (1.50; 95% CI
      1.29 to 1.73). The HRs for IBS in children with UTI were greater for those with
      more UTI-related medical visits/per year (>5 visits, HR 61.3; 95% CI 51.8 to
      72.6), with longer length of stay of hospitalization (>7 days, HR 1.75; 95% CI
      1.36 to 2.24) and with vesicoureteral reflux (VUR) (HR 1.73; 95% CI 1.35 to 2.22)
      (p<0.0001, the trend test). Infants with UTI had higher risks of childhood IBS
      and the risks elevated further with recurrent UTI or UTI with concurrent VUR.

PMID- 29588333
TI  - Case-control investigation of occupational exposure to chlorinated solvents and
      non-Hodgkin's lymphoma.
AB  - OBJECTIVES: Although many studies have investigated the association between
      trichloroethylene (TCE) exposure and non-Hodgkin's lymphoma (NHL), less is known
      about other chlorinated solvents. We extended our previous analysis of
      occupational TCE exposure in a multicentre population-based case-control study of
      NHL to investigate associations with five additional chlorinated solvents: 1,1,1,
      trichloroethane, carbon tetrachloride, chloroform, methylene chloride and
      perchloroethylene. METHODS: Cases (n=1189) and controls (n=982) provided detailed
      information on their occupational histories and workplace exposure to chlorinated
      solvents for selected occupations using job-specific interview modules. An
      industrial hygienist used this information and a review of the literature to
      assess occupational exposure to chlorinated solvents. We computed ORs and 95% CIs
      for different exposure metrics, with the unexposed group as the referent. We also
      computed ORs by NHL subtype. RESULTS: High cumulative hours exposed to carbon
      tetrachloride was associated with NHL (>520 hours: OR 1.9; 95% CI 1.0 to 3.6;
      Ptrend=0.04). This association remained after restricting to jobs with high
      intensity exposure (OR 2.0; 95% CI 1.1 to 3.8; P=0.03) and >=90% exposure
      probability (OR 2.1; 95% CI 1.0 to 4.3; P=0.03), adjusting for TCE (OR 2.1; 95%
      CI 1.0- to 4.1; P=0.04) and incorporating a 15-year lag (OR 1.9; 95% CI 1.0 to
      3.6; P=0.06). The other evaluated chlorinated solvents were not associated with
      NHL. CONCLUSIONS: This is the first study using high-quality quantitative
      exposure assessment methods to identify a statistically significant elevated
      association between occupational exposure to carbon tetrachloride and NHL. Our
      findings, although limited by a small number of exposed cases, offer evidence
      that carbon tetrachloride may be a lymphomagen.

PMID- 29588334
TI  - How do you treat this diversion ileitis and pouchitis?

PMID- 29588335
TI  - The Potato MAP3K StVIK Is Required for the Phytophthora infestans RXLR Effector
      Pi17316 to Promote Disease.
AB  - Plant pathogens deliver effectors to manipulate processes in their hosts,
      creating a suitable environment for invasion and proliferation. Yet, little is
      known about the host proteins that are targeted by effectors from filamentous
      pathogens. Here, we show that stable transgenic expression in potato (Solanum
      tuberosum) and transient expression in Nicotiana benthamiana of the arginine-any
      amino acid-leucine-arginine effector Pi17316 enhances leaf colonization by the
      late blight pathogen Phytophthora infestans Expression of Pi17316 also attenuates
      cell death triggered by the pathogen-associated molecular pattern Infestin1
      (INF1), indicating that the effector suppresses pattern-triggered immunity.
      However, this effector does not attenuate cell death triggered by a range of
      resistance proteins, showing that it specifically suppresses INF1-triggered cell
      death (ICD). In yeast two-hybrid assays, Pi17316 interacts directly with the
      potato ortholog of VASCULAR HIGHWAY1-interacting kinase (StVIK), encoding a
      predicted MEK kinase (MAP3K). Interaction in planta was confirmed by
      coimmunoprecipitation and occurs at the plant plasma membrane. Virus-induced gene
      silencing of VIK in N. benthamiana attenuated P. infestans colonization, whereas
      transient overexpression of StVIK enhanced colonization, indicating that this
      host protein acts as a susceptibility factor. Moreover, VIK overexpression
      specifically attenuated ICD, indicating that it is a negative regulator of
      immunity. The abilities of Pi17316 to enhance P. infestans colonization or
      suppress ICD were compromised significantly in NbVIK-silenced plants,
      demonstrating that the effector activity of Pi17316 is mediated by this MAP3K.
      Thus, StVIK is exploited by P. infestans as a susceptibility factor to promote
      late blight disease.

PMID- 29588336
TI  - Measurement of Gross Photosynthesis, Respiration in the Light, and Mesophyll
      Conductance Using H218O Labeling.
AB  - A fundamental challenge in plant physiology is independently determining the
      rates of gross O2 production by photosynthesis and O2 consumption by respiration,
      photorespiration, and other processes. Previous studies on isolated chloroplasts
      or leaves have separately constrained net and gross O2 production (NOP and GOP,
      respectively) by labeling ambient O2 with 18O while leaf water was unlabeled.
      Here, we describe a method to accurately measure GOP and NOP of whole detached
      leaves in a cuvette as a routine gas-exchange measurement. The petiole is
      immersed in water enriched to a delta18O of ~9,0000/00, and leaf water is labeled
      through the transpiration stream. Photosynthesis transfers 18O from H2O to O2 GOP
      is calculated from the increase in delta18O of O2 as air passes through the
      cuvette. NOP is determined from the increase in O2/N2 Both terms are measured by
      isotope ratio mass spectrometry. CO2 assimilation and other standard gas-exchange
      parameters also were measured. Reproducible measurements are made on a single
      leaf for more than 15 h. We used this method to measure the light response curve
      of NOP and GOP in French bean (Phaseolus vulgaris) at 21% and 2% O2 We then used
      these data to examine the O2/CO2 ratio of net photosynthesis, the light response
      curve of mesophyll conductance, and the apparent inhibition of respiration in the
      light (Kok effect) at both oxygen levels. The results are discussed in the
      context of evaluating the technique as a tool to study and understand leaf
      physiological traits.

PMID- 29588337
TI  - Psychosocial Effects of Parent-Child Book Reading Interventions: A Meta-analysis.
AB  - CONTEXT: Parent-child book reading (PCBR) is effective at improving young
      children's language, literacy, brain, and cognitive development. The psychosocial
      effects of PCBR interventions are unclear. OBJECTIVE: To systematically review
      and synthesize the effects of PCBR interventions on psychosocial functioning of
      children and parents. DATA SOURCES: We searched ERIC, PsycINFO, Medline, Embase,
      PubMed, Applied Social Sciences Index and Abstracts, Social Services Abstracts,
      Sociological Abstracts, Family and Society Studies Worldwide, and Social Work
      Abstracts. We hand searched references of previous literature reviews. STUDY
      SELECTION: Randomized controlled trials. DATA EXTRACTION: By using a standardized
      coding scheme, data were extracted regarding sample, intervention, and study
      characteristics. RESULTS: We included 19 interventions (3264 families). PCBR
      interventions improved the psychosocial functioning of children and parents
      compared with controls (standardized mean difference: 0.185; 95% confidence
      interval: 0.077 to 0.293). The assumption of homogeneity was rejected (Q =
      40.010; P < .01). Two moderator variables contributed to between-group variance:
      method of data collection (observation less than interview; Qb = 7.497; P < .01)
      and rater (reported by others less than self-reported; Qb = 21.368; P < .01).
      There was no significant difference between effects of PCBR interventions on
      psychosocial outcomes of parents or children (Qb = 0.376; P = .540). LIMITATIONS:
      The ratio of moderating variables to the included studies limited interpretation
      of the findings. CONCLUSIONS: PCBR interventions are positively and significantly
      beneficial to the psychosocial functioning of both children and parents.

PMID- 29588338
TI  - Squaring the Curve of Cardiovascular Health From the Beginning of Life.

PMID- 29588339
TI  - Selective Prostacyclin Receptor Agonist Selexipag, in Contrast to Prostacyclin
      Analogs, Does Not Evoke Paradoxical Vasoconstriction of the Rat Femoral Artery.
AB  - Selexipag [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N
      (methylsulfonyl)acetamide] is a selective nonprostanoid prostacyclin (PGI2)
      receptor (IP receptor) agonist that is approved for the treatment of pulmonary
      arterial hypertension (PAH). In contrast to selexipag, PGI2 analogs used in the
      clinic are nonselective agonists at prostanoid receptors and can also activate
      contractile prostaglandin E receptor 3 (EP3) receptors. Leg pain is a common side
      effect in patients receiving treatment with PGI2 analogs and peripheral
      vasoconstriction can be responsible for side effects related to muscular
      ischemia. This study tested the hypothesis that PGI2 analogs could cause
      paradoxical vasoconstriction of the femoral artery via EP3 receptor activation
      but that only vasorelaxation would be observed in response to selexipag and its
      active metabolite ACT-333679 [{4-[(5,6-diphenylpyrazin-2
      yl)(isopropyl)amino]butoxy}acetic acid]. Selexipag and ACT-333679 relaxed rings
      of the isolated rat femoral artery contracted with either prostaglandin F2alpha
      (PGF2alpha ) or the alpha1 adrenoceptor (alpha1AR) agonist phenylephrine. ACT
      333679 also inhibited contraction of the femoral artery to sympathetic nerve
      stimulation. In contrast, PGI2 analogs (iloprost, beraprost, and treprostinil)
      caused additional contraction of arterial rings precontracted with phenylephrine,
      which was reverted to relaxation by antagonism of EP3 receptors. Treprostinil
      augmented contraction of the femoral artery to sympathetic nerve stimulation in
      an EP3 receptor-dependent manner. Mechanistically, concomitant EP3 and alpha1AR
      receptor activation synergistically constricted femoral arteries. It is concluded
      that selexipag and ACT-333679 are vasorelaxants of the rat femoral artery and,
      unlike PGI2 analogs, do not cause paradoxical vasoconstriction via activation of
      EP3 receptors. EP3 receptor-mediated vasoconstriction may contribute to the well
      documented peripheral muscle pain reported in patients with PAH receiving PGI2
      analogs. Leg pain may be less in patients treated with selexipag.

PMID- 29588340
TI  - XZ-1 regulates cell apoptosis of gastric epithelial dysplasia via NF
      kappaB/p53/Ki67 signaling pathway.
AB  - We aimed to determine the effect of 'Xiaozeng No. 1' (XZ-1) on cellular apoptosis
      changes of gastric epithelial dysplasia (GED) and to explore the underlying
      mechanism. Specimens taken from the pyloric area of the stomachs from rats in
      each group were subjected to Hematoxylin and Eosin (H&E) staining for
      pathological examination, TUNEL staining for apoptosis detection, and Western
      blot analysis for apoptosis-related proteins. The results showed that XZ-1
      decreased GED incidence and enhanced gastric epithelial apoptosis. Furthermore,
      XZ-1 up-regulated the proapoptotic proteins including cleaved caspases (cysteine
      dependent aspartate-specific protease) (-3, -8, and -9), Fas, Bax, and Bid, and
      facilitated the release of cytochrome c from mitochondria to the cytoplasm.
      Interestingly, XZ-1 enhanced protein expression of NF-kappaB p65, Ki67, and p53.
      Moreover, inhibition of NF-kappaB pathway suppressed the XZ-induced p53
      expression, whereas inhibition of NF-kappaB or p53 pathway suppressed the XZ
      induced Ki67. More importantly, inhibition of NF-kappaB or p53 pathway attenuated
      the XZ-1-mediated induction of gastric epithelial apoptosis and decline of GED
      incidence. Collectively, our results demonstrated that XZ-1, almost equivalent
      effect exerted by the positive control Retin-A, dramatically decreased GED
      incidence and enhanced gastric epithelial apoptosis. Meanwhile, XZ-1 activated
      the NF-kappaB/p53/Ki67-apoptosis signaling pathway, which might be one of the
      mechanisms whereby XZ-1 reversed GED.

PMID- 29588341
TI  - Homeostasis model assessment of insulin resistance in relation to the poor
      functional outcomes in nondiabetic patients with ischemic stroke.
AB  - Whether insulin resistance (IR) predicts worse functional outcome in ischemic
      stroke is still a matter of debate. The aim of the present study is to determine
      the association between IR and risk of poor outcome in 173 Chinese nondiabetic
      patients with acute ischemic stroke. This is a prospective, population-based
      cohort study. Insulin sensitivity, expressed by the homeostasis model assessment
      (HOMA) of insulin sensitivity (HOMA index = (fasting insulin * fasting
      glucose)/22.5). IR was defined by HOMA-IR index in the top quartile (Q4).
      Functional impairment was evaluated at discharge using the modified Rankin scale
      (mRS). The median (interquartile range) HOMA-IR was 2.14 (1.17-2.83), and Q4 was
      at least 2.83. There was a significantly positive correlation between HOMA-IR and
      National Institutes of Health Stroke Scale (r = 0.408; P<0.001). In multivariate
      analyses, patients in IR group were associated with a higher risk of poor
      functional outcome (odds ratio (OR) = 3.23; 95% confidence interval (CI) = 1.75
      5.08; P=0.001). In multivariate models comparing the third and fourth quartiles
      against the first quartile of the HOMA-IR, levels of HOMA-IR were associated with
      poor outcome, and the adjusted risk of poor outcome increased by 207% (OR = 3.05
      (95% CI 1.70-4.89), P=0.006) and 429% (5.29 (3.05-9.80), P<0.001). In a receiver
      operating characteristic curve (ROC) analysis of poor outcome, the area under the
      curve (AUC) increased from 0.80 to 0.84 (95% CI: 0.79-0.88) by adding HOMA-IR to
      clinical examination variables (P=0.02). High HOMA-IR index is associated with a
      poor functional outcome in nondiabetic patients with acute ischemic stroke.

PMID- 29588342
TI  - Matrix-bound AGEs enhance TGFbeta2-mediated mesenchymal transition of lens
      epithelial cells via the noncanonical pathway: implications for secondary
      cataract formation.
AB  - Advanced glycation end products (AGEs) are post-translational modifications
      formed from the reaction of reactive carbonyl compounds with amino groups in
      proteins. Our laboratory has previously shown that AGEs in extracellular matrix
      (ECM) proteins promote TGFbeta2 (transforming growth factor-beta 2)-mediated
      epithelial-to-mesenchymal transition (EMT) of lens epithelial cells (LECs), which
      could play a role in fibrosis associated with posterior capsule opacification. We
      have also shown that alphaB-crystallin plays an important role in TGFbeta2
      mediated EMT of LECs. Here, we investigated the signaling mechanisms by which ECM
      AGEs enhance TGFbeta2-mediated EMT in LECs. We found that in LECs cultured on AGE
      modified basement protein extract (AGE-BME), TGFbeta2 treatment up-regulated the
      mesenchymal markers alpha-SMA (alpha-smooth muscle actin) and alphaB-crystallin
      and down-regulated the epithelial marker E-cadherin more than LECs cultured on
      unmodified BME and treated with TGFbeta2. Using a Multiplex Assay, we found that
      AGE-BME significantly up-regulated the noncanonical pathway by promoting
      phosphorylation of ERK (extracellular signal-regulated kinases), AKT, and p38
      MAPK (mitogen-activated protein kinases) during TGFbeta2-mediated EMT. This EMT
      response was strongly suppressed by inhibition of AKT and p38 MAPK
      phosphorylation. The AKT inhibitor LY294002 also suppressed TGFbeta2-induced up
      regulation of nuclear Snail and reduced phosphorylation of GSK3beta. Inhibition
      of Snail expression suppressed TGFbeta2-mediated alpha-SMA expression. alphaB
      Crystallin was up-regulated in an AKT-dependent manner during AGE-BME/TGFbeta2
      mediated EMT in LECs. The absence of alphaB-crystallin in LECs suppressed
      TGFbeta2-induced GSK3beta phosphorylation, resulting in lower Snail levels. Taken
      together, these results show that ECM-AGEs enhance the TGFbeta2-mediated EMT
      response through activation of the AKT/Snail pathway, in which alphaB-crystallin
      plays an important role as a linker between the TGFbeta2 and AGE-mediated
      signaling pathways.

PMID- 29588343
TI  - Ionotropic and Metabotropic Mechanisms of Allosteric Modulation of alpha7
      Nicotinic Receptor Intracellular Calcium.
AB  - The pharmacological targeting of the alpha7 nicotinic acetylcholine receptor
      (alpha7) is a promising strategy in the development of new drugs for neurologic
      diseases. Because alpha7 receptors regulate cellular calcium, we investigated how
      the prototypical type II-positive allosteric modulator PNU120596 affects alpha7
      mediated calcium signaling. Live imaging experiments show that PNU120596 augments
      ryanodine receptor-driven calcium-induced calcium release (CICR), inositol
      induced calcium release (IICR), and phospholipase C activation by the alpha7
      receptor. Both influx of calcium through the alpha7 nicotinic acetylcholine
      receptor (nAChR) channel as well as the binding of intracellular G proteins were
      involved in the effect of PNU120596 on intracellular calcium. This is evidenced
      by the findings that chelation of extracellular calcium, expression of alpha7D44A
      or alpha7345-348A mutant subunits, or blockade of calcium store release
      compromised the ability of PNU120596 to increase intracellular calcium transients
      generated by alpha7 ligand activation. Spatiotemporal stochastic modeling of
      calcium transient responses corroborates these results and indicates that alpha7
      receptor activation enables calcium microdomains locally and to lesser extent in
      the distant cytosol. From the model, allosteric modulation of the receptor
      activates CICR locally via ryanodine receptors and augments IICR through enhanced
      calcium influx due to prolonged alpha7 nAChR opening. These findings provide a
      new mechanistic framework for understanding the effect of alpha7 receptor
      allosteric modulation on both local and global calcium dynamics.

PMID- 29588344
TI  - No Matter Where, Adolescent Sexual Health Is Everyone's Job.

PMID- 29588345
TI  - Documentation of Sexual History in Hospitalized Adolescents on the General
      Pediatrics Service.
AB  - OBJECTIVES: To determine the frequency of sexual history taking and the
      associated characteristics of hospitalized adolescents in the pediatric
      hospitalist service. METHODS: A retrospective chart review of adolescents 14 to
      18 years old who were admitted to the pediatric hospitalist service at an urban,
      academic children's hospital in the Northeast from 2013 to 2015 was conducted.
      Repeat admissions, admissions to specialty services, and charts that noted
      impairment because of psychosis, cognitive delay, or illness severity were
      excluded. For charts that met the criteria, the admission history and physical
      was carefully reviewed for a notation of sexual history. For those with
      documentation, sexual activity status and a risk level assessment were recorded.
      Patient demographics and admission characteristics were extracted. chi2 tests and
      logistic regression were used to examine differences between those with sexual
      history and those without. RESULTS: A total of 752 charts met the criteria for
      inclusion. The majority of adolescents were girls (n = 506; 67.3%); the mean age
      was 15.7 years (SD = 1.2). Girls had 2.99 (95% confidence interval [CI] 2.18
      4.11) higher odds of documentation than boys, and older adolescents had 1.41 (95%
      CI 1.03-1.91) higher odds than younger adolescents. Documentation did not differ
      significantly on the basis of admission type (medical or psychiatric), admission
      time, patient race and/or ethnicity, or provider gender. Among those with a
      documented sexual history, risk-level details were often omitted. CONCLUSIONS:
      Sexual history taking does not occur universally for hospitalized adolescents.
      Girls were screened more often than boys despite similar rates of sexual
      activity. The inpatient admission may be a missed opportunity for harm-reduction
      counseling and adherence to sexually transmitted infection testing guidelines.

PMID- 29588346
TI  - Microbial symbionts regulate the primary Ig repertoire.
AB  - The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal
      immune fitness. Early events that shape preimmune Ig repertoires, expressed on
      IgM+ IgD+ B cells as B cell receptors (BCRs), are poorly defined. Here, we
      studied germ-free mice and conventionalized littermates to explore the hypothesis
      that symbiotic microbes help shape the preimmune Ig repertoire. Ig-binding assays
      showed that exposure to conventional microbial symbionts enriched frequencies of
      antibacterial IgM+ IgD+ B cells in intestine and spleen. This enrichment affected
      follicular B cells, involving a diverse set of Ig-variable region gene segments,
      and was T cell-independent. Functionally, enrichment of microbe reactivity primed
      basal levels of small intestinal T cell-independent, symbiont-reactive IgA and
      enhanced systemic IgG responses to bacterial immunization. These results
      demonstrate that microbial symbionts influence host immunity by enriching
      frequencies of antibacterial specificities within preimmune B cell repertoires
      and that this may have consequences for mucosal and systemic immunity.

PMID- 29588347
TI  - Termination of T cell priming relies on a phase of unresponsiveness promoting
      disengagement from APCs and T cell division.
AB  - T cells are primed in secondary lymphoid organs by establishing stable
      interactions with antigen-presenting cells (APCs). However, the cellular
      mechanisms underlying the termination of T cell priming and the initiation of
      clonal expansion remain largely unknown. Using intravital imaging, we observed
      that T cells typically divide without being associated to APCs. Supporting these
      findings, we demonstrate that recently activated T cells have an intrinsic defect
      in establishing stable contacts with APCs, a feature that was reflected by a
      blunted capacity to stop upon T cell receptor (TCR) engagement. T cell
      unresponsiveness was caused, in part, by a general block in extracellular calcium
      entry. Forcing TCR signals in activated T cells antagonized cell division,
      suggesting that T cell hyporesponsiveness acts as a safeguard mechanism against
      signals detrimental to mitosis. We propose that transient unresponsiveness
      represents an essential phase of T cell priming that promotes T cell
      disengagement from APCs and favors effective clonal expansion.

PMID- 29588348
TI  - Intratumoral CpG-B Promotes Antitumoral Neutrophil, cDC, and T-cell Cooperation
      without Reprograming Tolerogenic pDC.
AB  - Cancer immunotherapies utilize distinct mechanisms to harness the power of the
      immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing
      active immune responses against an existing cancer, are highly dependent on the
      immunological microenvironment, where many immune cell types display high levels
      of plasticity and, depending on the context, promote very different immunologic
      outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly
      immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor
      microenvironment. Here, we report that intratumoral (i.t.) injection of
      established solid tumors with CpG oligonucleotides-B (CpG-B) inhibits tumor
      growth. Interestingly, control of tumor growth was independent of tumor
      associated pDC, which remained refractory to CpG-B stimulation and whose
      depletion did not alter the efficacy of the treatment. Instead, tumor growth
      inhibition subsequent to i.t. CpG-B injection depended on the recruitment of
      neutrophils into the milieu, resulting in the activation of conventional
      dendritic cells, subsequent increased antitumor T-cell priming in draining lymph
      nodes, and enhanced effector T-cell infiltration in the tumor microenvironment.
      These results reinforce the concept that i.t. delivery of TLR9 agonists alters
      the tumor microenvironment by improving the antitumor activity of both innate and
      adaptive immune cells.Significance: Intratumoral delivery of CpG-B disrupts the
      tolerogenic tumor microenvironment and inhibits tumor growth. Cancer Res; 78(12);
      3280-92. (c)2018 AACR.

PMID- 29588349
TI  - IkappaB Kinase alpha Is Required for Development and Progression of KRAS-Mutant
      Lung Adenocarcinoma.
AB  - Although oncogenic activation of NFkappaB has been identified in various tumors,
      the NFkappaB-activating kinases (inhibitor of NFkappaB kinases, IKK) responsible
      for this are elusive. In this study, we determined the role of IKKalpha and
      IKKbeta in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane
      and by respiratory epithelial expression of oncogenic KRASG12D Using NFkappaB
      reporter mice and conditional deletions of IKKalpha and IKKbeta, we identified
      two distinct early and late activation phases of NFkappaB during chemical and
      genetic lung adenocarcinoma development, which were characterized by nuclear
      translocation of RelB, IkappaBbeta, and IKKalpha in tumor-initiated cells.
      IKKalpha was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung
      adenocarcinoma, and respiratory epithelial IKKalpha-deficient mice were markedly
      protected from the disease. IKKalpha specifically cooperated with mutant KRAS for
      tumor induction in a cell-autonomous fashion, providing mutant cells with a
      survival advantage in vitro and in vivo IKKalpha was highly expressed in human
      lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK
      function delivered superior effects against KRAS-mutant lung adenocarcinoma
      compared with a specific IKKbeta inhibitor. These results demonstrate an
      actionable requirement for IKKalpha in KRAS-mutant lung adenocarcinoma, marking
      the kinase as a therapeutic target against this disease.Significance: These
      findings report a novel requirement for IKKalpha in mutant KRAS lung tumor
      formation, with potential therapeutic applications. Cancer Res; 78(11); 2939-51.
      (c)2018 AACR.

PMID- 29588350
TI  - The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma.
AB  - Somatic copy number variations (CNV) may drive cancer progression through both
      coding and noncoding transcripts. However, noncoding transcripts resulting from
      CNV are largely unknown, especially for circular RNAs. By integrating
      bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma,
      we identify a proto-oncogenic circular RNA (circPRKCI) from the 3q26.2 amplicon,
      one of the most frequent genomic aberrations in multiple cancers. circPRKCI was
      overexpressed in lung adenocarcinoma tissues, in part due to amplification of the
      3q26.2 locus, and promoted proliferation and tumorigenesis of lung
      adenocarcinoma. circPRKCI functioned as a sponge for both miR-545 and miR-589 and
      abrogated their suppression of the protumorigenic transcription factor E2F7
      Intratumor injection of cholesterol-conjugated siRNA specifically targeting
      circPRKCI inhibited tumor growth in a patient-derived lung adenocarcinoma
      xenograft model. In summary, circPRKCI is crucial for tumorigenesis and may serve
      as a potential therapeutic target in patients with lung
      adenocarcinoma.Significance: These findings reveal high expression of the
      circular RNA circPRKCI drives lung adenocarcinoma tumorigenesis. Cancer Res;
      78(11); 2839-51. (c)2018 AACR.

PMID- 29588351
TI  - A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via
      Nuclear Sequestration of p53.
AB  - Long noncoding RNAs (lncRNA) have been associated with various types of cancer;
      however, the precise role of many lncRNAs in tumorigenesis remains elusive. Here
      we demonstrate that the cytosolic lncRNA P53RRA is downregulated in cancers and
      functions as a tumor suppressor by inhibiting cancer progression. Chromatin
      remodeling proteins LSH and Cfp1 silenced or increased P53RRA expression,
      respectively. P53RRA bound Ras GTPase-activating protein-binding protein 1
      (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of
      G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a
      G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to
      cell-cycle arrest, apoptosis, and ferroptosis. P53RRA promoted ferroptosis and
      apoptosis by affecting transcription of several metabolic genes. Low P53RRA
      expression significantly correlated with poor survival in patients with breast
      and lung cancers harboring wild-type p53. These data show that lncRNAs can
      directly interact with the functional domain of signaling proteins in the
      cytoplasm, thus regulating p53 modulators to suppress cancer
      progression.Significance: A cytosolic lncRNA functions as a tumor suppressor by
      activating the p53 pathway. Cancer Res; 78(13); 3484-96. (c)2018 AACR.

PMID- 29588352
TI  - Patterns, Perception and Behavior of Electronic Nicotine Delivery Systems Use and
      Multiple Product Use Among Young Adults.
AB  - BACKGROUND: Electronic nicotine delivery systems (ENDS) are battery-operated
      devices used to inhale vaporized or aerosolized nicotine. There is increasing
      research uncovering negative health effects of these devices. Less is known about
      the social and behavioral aspects among college students. METHODS: This cross
      sectional study was conducted at a mid-sized private university in Florida. The
      survey was sent via e-mail to the student body of undergraduates. A final sample
      size of 989 students was analyzed to understand demographic differences between
      users and nonusers, initiation factors, and influencers, as well as multiple
      product behaviors. RESULTS: Approximately 51.4% (n = 508) of participants
      reported ever using an ENDS and other tobacco consumption. Males were
      significantly more likely to be users of ENDS. Polytobacco use, or the use of
      multiple tobacco products, was also more common among participants who have tried
      ENDS (P < .001). Perceptions of harm of both the primary and secondary vapor were
      considered to be less than that of conventional cigarettes. Peers were the
      primary influencer for initial use. A 4-class latent variable model
      differentiated between usage patterns characterized as abstainers (70%), hookah
      users only (14%), ENDS only (11%), and polytobacco users (4%). CONCLUSIONS: ENDS
      are not commonly used as a quit tool among college students, but rather as a
      secondary source of nicotine, most commonly in current smokers.

PMID- 29588353
TI  - Erratum for Drusano et al., "Dilution Factor of Quantitative Bacterial Cultures
      Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated
      Bacterial Pneumonia".

PMID- 29588354
TI  - Erratum for Chen et al., "Chemogenomic Profiling of the Fungal Pathogen Candida
      albicans".

PMID- 29588355
TI  - Correction for Yang et al., "Tolerance to Caspofungin in Candida albicans Is
      Associated with at Least Three Distinctive Mechanisms That Govern Expression of
      FKS Genes and Cell Wall Remodeling".

PMID- 29588356
TI  - Is Colistin Susceptibility Testing Finally on the Right Track?

PMID- 29588358
TI  - Reply to Prim et al., "Is Colistin Susceptibility Testing Finally on the Right
      Track?"

PMID- 29588357
TI  - Successful Treatment of Persistent Burkholderia cepacia Complex Bacteremia with
      Ceftazidime-Avibactam.
AB  - We report our clinical experience treating a 2-month-old infant with congenital
      diaphragmatic hernia who experienced prolonged bacteremia with Burkholderia
      cepacia complex (Bcc) despite conventional antibiotic therapy and appropriate
      source control measures. The infection resolved after initiation of ceftazidime
      avibactam. Whole-genome sequencing revealed that the isolate most closely
      resembled B. contaminans and identified the mechanism of resistance that likely
      contributed to clinical cure with this agent. Ceftazidime-avibactam should be
      considered salvage therapy for Bcc infections if other treatment options have
      been exhausted.

PMID- 29588359
TI  - Antiphospholipid syndrome presenting as acute mesenteric venous thrombosis
      involving a variant inferior mesenteric vein and successful treatment with
      rivaroxaban.
AB  - Acute mesenteric venous thrombosis (MVT) is the rarest cause of acute mesenteric
      ischaemia, so thrombosis of a variant inferior mesenteric vein (IMV) is
      especially uncommon in the setting of antiphospholipid syndrome (APS). Here, we
      present such a case of seronegative APS initially manifesting as an anomalous IMV
      thrombosis in a 76-year-old woman. Although guidelines support anticoagulation
      with vitamin K antagonists in these patients, we anticoagulated with rivaroxaban
      (a direct oral anticoagulant (DOAC)) due to patient preference, which resulted in
      complete clinical and endoscopic resolution. IMV thrombosis is a rare form of
      MVT, only two case reports describe successful anticoagulation with DOACs in the
      setting of MVT and none report APS as an underlying aetiology. Therefore, this
      case provides the opportunity to review the pathophysiology of MVT, APS and their
      medical management including current trends in anticoagulation.

PMID- 29588360
TI  - taxMaps: comprehensive and highly accurate taxonomic classification of short-read
      data in reasonable time.
AB  - High-throughput sequencing is a revolutionary technology for the analysis of
      metagenomic samples. However, querying large volumes of reads against
      comprehensive DNA/RNA databases in a sensitive manner can be compute-intensive.
      Here, we present taxMaps, a highly efficient, sensitive, and fully scalable
      taxonomic classification tool. Using a combination of simulated and real
      metagenomics data sets, we demonstrate that taxMaps is more sensitive and more
      precise than widely used taxonomic classifiers and is capable of delivering
      classification accuracy comparable to that of BLASTN, but at up to three orders
      of magnitude less computational cost.

PMID- 29588361
TI  - Sequential regulatory activity prediction across chromosomes with convolutional
      neural networks.
AB  - Models for predicting phenotypic outcomes from genotypes have important
      applications to understanding genomic function and improving human health. Here,
      we develop a machine-learning system to predict cell-type-specific epigenetic and
      transcriptional profiles in large mammalian genomes from DNA sequence alone. By
      use of convolutional neural networks, this system identifies promoters and distal
      regulatory elements and synthesizes their content to make effective gene
      expression predictions. We show that model predictions for the influence of
      genomic variants on gene expression align well to causal variants underlying
      eQTLs in human populations and can be useful for generating mechanistic
      hypotheses to enable fine mapping of disease loci.

PMID- 29588362
TI  - Double insertion of transposable elements provides a substrate for the evolution
      of satellite DNA.
AB  - Eukaryotic genomes are replete with repeated sequences in the form of
      transposable elements (TEs) dispersed across the genome or as satellite arrays,
      large stretches of tandemly repeated sequences. Many satellites clearly
      originated as TEs, but it is unclear how mobile genetic parasites can transform
      into megabase-sized tandem arrays. Comprehensive population genomic sampling is
      needed to determine the frequency and generative mechanisms of tandem TEs, at all
      stages from their initial formation to their subsequent expansion and maintenance
      as satellites. The best available population resources, short-read DNA sequences,
      are often considered to be of limited utility for analyzing repetitive DNA due to
      the challenge of mapping individual repeats to unique genomic locations. Here we
      develop a new pipeline called ConTExt that demonstrates that paired-end Illumina
      data can be successfully leveraged to identify a wide range of structural
      variation within repetitive sequence, including tandem elements. By analyzing 85
      genomes from five populations of Drosophila melanogaster, we discover that TEs
      commonly form tandem dimers. Our results further suggest that insertion site
      preference is the major mechanism by which dimers arise and that, consequently,
      dimers form rapidly during periods of active transposition. This abundance of TE
      dimers has the potential to provide source material for future expansion into
      satellite arrays, and we discover one such copy number expansion of the DNA
      transposon hobo to approximately 16 tandem copies in a single line. The very
      process that defines TEs-transposition-thus regularly generates sequences from
      which new satellites can arise.

PMID- 29588363
TI  - Effects of hypo-O-GlcNAcylation on Drosophila development.
AB  - Post-translational modification of serine/threonine residues in nucleocytoplasmic
      proteins with GlcNAc (O-GlcNAcylation) is an essential regulatory mechanism in
      many cellular processes. In Drosophila, null mutants of the Polycomb gene O
      GlcNAc transferase (OGT; also known as super sex combs (sxc)) display homeotic
      phenotypes. To dissect the requirement for O-GlcNAc signaling in Drosophila
      development, we used CRISPR/Cas9 gene editing to generate rationally designed sxc
      catalytically hypomorphic or null point mutants. Of the fertile males derived
      from embryos injected with the CRISPR/Cas9 reagents, 25% produced progeny
      carrying precise point mutations with no detectable off-target effects. One of
      these mutants, the catalytically inactive sxcK872M , was recessive lethal,
      whereas a second mutant, the hypomorphic sxcH537A , was homozygous viable. We
      observed that reduced total protein O-GlcNAcylation in the sxcH537A mutant is
      associated with a wing vein phenotype and temperature-dependent lethality.
      Genetic interaction between sxcH537A and a null allele of Drosophila host cell
      factor (dHcf), encoding an extensively O-GlcNAcylated transcriptional
      coactivator, resulted in abnormal scutellar bristle numbers. A similar phenotype
      was also observed in sxcH537A flies lacking a copy of skuld (skd), a Mediator
      complex gene known to affect scutellar bristle formation. Interestingly, this
      phenotype was independent of OGT Polycomb function or dHcf downstream targets. In
      conclusion, the generation of the endogenous OGT hypomorphic mutant sxcH537A
      enabled us to identify pleiotropic effects of globally reduced protein O-GlcNAc
      during Drosophila development. The mutants generated and phenotypes observed in
      this study provide a platform for discovery of OGT substrates that are critical
      for Drosophila development.

PMID- 29588364
TI  - Spatially dependent alkyl quinolone signaling responses to antibiotics in
      Pseudomonas aeruginosa swarms.
AB  - There is a general lack of understanding about how communities of bacteria
      respond to exogenous toxins such as antibiotics. Most of our understanding of
      community-level stress responses comes from the study of stationary biofilm
      communities. Although several community behaviors and production of specific
      biomolecules affecting biofilm development and associated behavior have been
      described for Pseudomonas aeruginosa and other bacteria, we have little
      appreciation for the production and dispersal of secreted metabolites within the
      2D and 3D spaces they occupy as they colonize, spread, and grow on surfaces. Here
      we specifically studied the phenotypic responses and spatial variability of alkyl
      quinolones, including the Pseudomonas quinolone signal (PQS) and members of the
      alkyl hydroxyquinoline (AQNO) subclass, in P. aeruginosa plate-assay swarming
      communities. We found that PQS production was not a universal signaling response
      to antibiotics, as tobramycin elicited an alkyl quinolone response, whereas
      carbenicillin did not. We also found that PQS and AQNO profiles in response to
      tobramycin were markedly distinct and influenced these swarms on different
      spatial scales. At some tobramycin exposures, P. aeruginosa swarms produced alkyl
      quinolones in the range of 150 MUm PQS and 400 MUm AQNO that accumulated as
      aggregates. Our collective findings show that the distribution of alkyl
      quinolones can vary by several orders of magnitude within the same swarming
      community. More notably, our results suggest that multiple intercellular signals
      acting on different spatial scales can be triggered by one common cue.

PMID- 29588365
TI  - A three-way inter-molecular network accounts for the CaValpha2delta1-induced
      functional modulation of the pore-forming CaV1.2 subunit.
AB  - L-type CaV1.2 channels are essential for the excitation-contraction coupling in
      cardiomyocytes and are hetero-oligomers of a pore-forming CaValpha1C assembled
      with CaVbeta and CaValpha2delta1 subunits. A direct interaction between
      CaValpha2delta1 and Asp-181 in the first extracellular loop of CaValpha1
      reproduces the native properties of the channel. A 3D model of the von Willebrand
      factor type A (VWA) domain of CaValpha2delta1 complexed with the voltage sensor
      domain of CaValpha1C suggests that Ser-261 and Ser-263 residues in the metal ion
      dependent adhesion site (MIDAS) motif are determinant in this interaction, but
      this hypothesis is untested. Here, coimmunoprecipitation assays and patch-clamp
      experiments of single-substitution variants revealed that CaValpha2delta1 Asp-259
      and Ser-261 are the two most important residues in regard to protein interactions
      and modulation of CaV1.2 currents. In contrast, mutating the side chains of
      CaValpha2delta1 Ser-263, Thr-331, and Asp-363 with alanine did not completely
      prevent channel function. Molecular dynamics simulations indicated that the
      carboxylate side chain of CaValpha2delta1 Asp-259 coordinates the divalent cation
      that is further stabilized by the oxygen atoms from the hydroxyl side chain of
      CaValpha2delta1 Ser-261 and the carboxylate group of CaValpha1C Asp-181. In
      return, the hydrogen atoms contributed by the side chain of Ser-261 and the main
      chain of Ser-263 bonded the oxygen atoms of CaV1.2 Asp-181. We propose that
      CaValpha2delta1 Asp-259 promotes Ca2+ binding necessary to produce the
      conformation of the VWA domain that locks CaValpha2delta1 Ser-261 and Ser-263
      within atomic distance of CaValpha1C Asp-181. This three-way network appears to
      account for the CaValpha2delta1-induced modulation of CaV1.2 currents.

PMID- 29588366
TI  - The long noncoding RNA lncZic2 drives the self-renewal of liver tumor-initiating
      cells via the protein kinase C substrates MARCKS and MARCKSL1.
AB  - Liver tumor-initiating cells (TICs) form small subsets of cells in hepatocellular
      tumors and account for tumorigenesis, metastasis, recurrence, and drug
      resistance. Recently, we found that the transcription factor Zic family member 2
      (ZIC2) is highly expressed in liver TICs and required for their self-renewal.
      However, the molecular mechanisms underlying self-renewal of liver TICs remain
      unclear. Here, using expression profiling and CRISPR-interference assays with
      clinical samples of human liver cancers, we identified a long noncoding RNA
      (lncRNA), lncZic2, that is located near the ZIC2 locus and was highly expressed
      in liver cancer and liver TICs. We found that lncZic2 is required for the self
      renewal of liver TICs in a ZIC2-independent manner. lncZic2 drove the expression
      of myristoylated alanine-rich protein kinase C substrate (MARCKS) and MARCKS-like
      1 (MARCKSL1), whose expression levels were increased during liver tumorigenesis
      and liver TIC self-renewal. Mechanistically, lncZic2 interacted with BRM/SWI2
      related gene 1 (BRG1) and recruited this transcriptional regulator to the
      promoters of the MARCKS and MARCKSL1 gene, which activated expression of these
      genes. Moreover, we noted that depletion of lncZic2 and BRG1 decreases MARCKS and
      MARCKSL1 expression and diminishes liver TIC levels. In conclusion, lncZic2 is
      required for the self-renewal of liver TICs by up-regulating MARCKS and MARCKSL1
      gene expression via the transcription factor BRG1. Our findings suggest that the
      lncZic2-BRG1-MARCKS/MARCKSL1 signaling cascade might be a potential target for
      eliminating liver TICs in the management of liver cancer.

PMID- 29588367
TI  - A cassette of basic amino acids in histone H2B regulates nucleosome dynamics and
      access to DNA damage.
AB  - Nucleosome dynamics, such as spontaneous DNA unwrapping, are postulated to have a
      critical role in regulating the access of DNA repair machinery to DNA lesions
      within nucleosomes. However, the specific histone domains that regulate
      nucleosome dynamics and the impact of such changes in intrinsic nucleosome
      dynamics on DNA repair are not well understood. Previous studies identified a
      highly conserved region in the N-terminal tail of histone H2B known as the
      histone H2Brepression (or HBR) domain, which has a significant influence on gene
      expression, chromatin assembly, and DNA damage formation and repair. However, the
      molecular mechanism(s) that may account for these observations are limited. In
      this study, we characterized the stability and dynamics of DeltaHBR mutant
      nucleosome core particles (NCPs) in vitro by restriction enzyme accessibility
      (REA), FRET, and temperature-induced sliding of histone octamers. Our results
      indicate that DeltaHBR-NCPs are more dynamic, with a larger steady-state fraction
      of the NCP population occupying the unwrapped state than for WT-NCPs.
      Additionally, DeltaHBR-histone octamers are more susceptible to temperature
      induced sliding on DNA than WT histone octamers. Furthermore, we show that the
      activity of base excision repair enzymes at uracil lesions and single nucleotide
      gaps is enhanced in a site-specific manner in DeltaHBR-NCPs. This enhanced
      activity correlates well with regions exhibiting increased DNA unwrapping.
      Finally, removal of the HBR domain is not sufficient to completely alleviate the
      structural constraints imposed by histone octamers on the activity of base
      excision repair enzymes.

PMID- 29588368
TI  - CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian
      gene expression in peripheral tissues.
AB  - Circadian locomotor output cycles kaput (CLOCK) is a transcription factor that
      activates transcription of clock-controlled genes by heterodimerizing with BMAL1
      and binding to E-box elements on DNA. Although several phosphorylation sites on
      CLOCK have already been identified, this study characterizes a novel
      phosphorylation site at serine 845 (Ser-836 in humans). Here, we show that CLOCK
      is a novel AKT substrate in vitro and in cells, and this phosphorylation site is
      a negative regulator of CLOCK nuclear localization by acting as a binding site
      for 14-3-3 proteins. To examine the role of CLOCK phosphorylation in vivo,
      ClockS845A knockin mice were generated using CRISPR/Cas9 technology. ClockS845A
      mice are essentially normal with normal central circadian rhythms and
      hemodynamics. However, examination of core circadian gene expression from
      peripheral tissues demonstrated that ClockS845A mice have diminished expression
      of Per2, Reverba, Dbp, and Npas2 in skeletal muscle and Per2, Reverba, Dbp, Per1,
      Rora, and Npas2 in the liver during the circadian cycle. The reduction in Dbp
      levels is associated with reduced H3K9ac at E-boxes where CLOCK binds despite no
      change in total CLOCK levels. Thus, CLOCK phosphorylation by AKT on Ser-845
      regulates its nuclear translocation and the expression levels of certain core
      circadian genes in insulin-sensitive tissues.

PMID- 29588371
TI  - The precious cell block.

PMID- 29588369
TI  - Phospholipid subcellular localization and dynamics.
AB  - Membrane biology seeks to understand how lipids and proteins within bilayers
      assemble into large structures such as organelles and the plasma membranes.
      Historically, lipids were thought to merely provide structural support for
      bilayer formation and membrane protein function. Research has now revealed that
      phospholipid metabolism regulates nearly all cellular processes. Sophisticated
      techniques helped identify >10,000 lipid species suggesting that lipids support
      many biological processes. Here, we highlight the synthesis of the most abundant
      glycerophospholipid classes and their distribution in organelles. We review
      vesicular and nonvesicular transport pathways shuttling lipids between organelles
      and discuss lipid regulators of membrane trafficking and second messengers in
      eukaryotic cells.

PMID- 29588370
TI  - Intrinsic properties and plasma membrane trafficking route of Src family kinase
      SH4 domains sensitive to retargeting by HIV-1 Nef.
AB  - The HIV type 1 pathogenicity factor Nef enhances viral replication by modulating
      multiple host cell pathways, including tuning the activation state of infected
      CD4 T lymphocytes to optimize virus spread. For this, Nef inhibits anterograde
      transport of the Src family kinase (SFK) Lck toward the plasma membrane (PM).
      This leads to retargeting of the kinase to the trans-Golgi network, whereas the
      intracellular transport of a related SFK, Fyn, is unaffected by Nef. The 18-amino
      acid Src homology 4 (SH4) domain membrane anchor of Lck is necessary and
      sufficient for Nef-mediated retargeting, but other details of this process are
      not known. The goal of this study was therefore to identify characteristics of
      SH4 domains responsive to Nef and the transport machinery used. Screening a panel
      of SFK SH4 domains revealed two groups that were sensitive or insensitive for
      trans-Golgi network retargeting by Nef as well as the importance of the amino
      acid at position 8 for determining Nef sensitivity. Anterograde transport of Nef
      sensitive domains was characterized by slower delivery to the PM and initial
      targeting to Golgi membranes, where transport was arrested in the presence of
      Nef. For Nef-sensitive SH4 domains, ectopic expression of the lipoprotein binding
      chaperone Unc119a or the GTPase Arl3 or reduction of their endogenous expression
      phenocopied the effect of Nef. Together, these results suggest that, analogous to
      K-Ras, Nef-sensitive SH4 domains are transported to the PM by a cycle of
      solubilization and membrane insertion and that intrinsic properties define SH4
      domains as cargo of this Nef-sensitive lipoprotein binding chaperone-GTPase
      transport cycle.

PMID- 29588373
TI  - FOXO3a expression is associated with lymph node metastasis and poor disease-free
      survival in triple-negative breast cancer.
AB  - AIMS: Forkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a,
      FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent
      studies have suggested that FOXOs act as tumour suppressors in a variety of human
      cancers. This study investigated the clinicopathological significance of FOXOs in
      triple-negative breast cancer (TNBC). METHODS: FOXO protein expressions were
      assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO
      protein expression and various clinicopathological parameters, including
      patients' survival, were investigated. MDA-MB-468 cell line was used for in vitro
      cell proliferation and migration assay. RESULTS: FOXO1 protein expression was not
      observed in all 125 TNBC tissues. FOXO4 and FOXO6 protein expressions were
      detected in 11 (8.8%) and 14 (11.2%) TNBC tissues, respectively. Loss of FOXO4
      expression was significantly associated with high histological grade (P=0.014,
      chi2 test), and TNBCs with positive FOXO6 expression correlated with high grade
      (P=0.020, chi2 test). FOXO3a expression was detected in 40 (32%) TNBC cases and
      correlated with adverse clinicopathological features, such as lymph node
      metastasis (P=0.021, chi2 test), perineural invasion (P=0.013, chi2 test) and
      higher Ki-67 proliferation index (P=0.048, t-test). Additionally, FOXO3a
      expression was significantly associated with poor disease-free survival (P=0.015,
      log-rank test). In the in vitro study, siRNA-mediated FOXO3a knockdown in the MDA
      MB-468 cell line inhibited cell proliferation and migration. CONCLUSION: Among
      FOXO members, FOXO3a may have a potential role in promoting tumour cell migration
      and proliferation and may serve as a prognostic biomarker and a potential
      therapeutic target for TNBC.

PMID- 29588372
TI  - Prognostic value of Ki67 analysed by cytology or histology in primary breast
      cancer.
AB  - AIMS: The accuracy of biomarker assessment in breast pathology is vital for
      therapy decisions. The therapy predictive and prognostic biomarkers oestrogen
      receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene
      expression profiling of breast cancer. The aims of this study were to investigate
      the concordance of consecutive biomarker assessment by immunocytochemistry on
      preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on
      the corresponding resected breast tumours. Further, to investigate the
      concordance with molecular subtype and correlation to stage and outcome. METHODS:
      Two retrospective cohorts comprising 385 breast tumours with clinicopathological
      data including gene expression-based subtype and up to 10-year overall survival
      data were evaluated. RESULTS: In both cohorts, we identified a substantial
      variation in Ki67 index between cytology and histology and a switch between low
      and high proliferation within the same tumour in 121/360 cases. ER evaluations
      were discordant in only 1.5% of the tumours. From cohort 2, gene expression data
      with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate
      classification could identify the correct molecular subtype in 60% and 64% of
      patients by cytology (n=63) and surgical resections (n=73), respectively.
      Furthermore, high Ki67 in surgical resections but not in cytology was associated
      with poor overall survival and higher probability for axillary lymph node
      metastasis. CONCLUSIONS: This study shows considerable differences in the
      prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic
      method. Furthermore, our findings show that both methods are insufficient in
      predicting true molecular subtypes.

PMID- 29588374
TI  - Flow cytometric minimal residual disease assessment of peripheral blood in acute
      lymphoblastic leukaemia patients has potential for early detection of relapsed
      extramedullary disease.
AB  - OBJECTIVES: To evaluate peripheral blood (PB) for minimal residual disease (MRD)
      assessment in adults with acute lymphoblastic leukaemia (ALL). METHODS: We
      analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for
      the presence of ALL MRD by six-colour flow cytometry (FC). RESULTS: The overall
      rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22%
      (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic
      cells in PB at the time of the extramedullary relapse that were interpreted as
      MRD-negative in BM. CONCLUSIONS: The use of PB MRD as a non-invasive method for
      monitoring of systemic relapse may have added clinical and diagnostic value in
      patients with high risk of extramedullary disease.

PMID- 29588375
TI  - A novel homozygous frameshift mutation in the FUCA1 gene causes both severe and
      mild fucosidosis.
AB  - AIMS: Fucosidosis is a rare autosomal recessive lysosomal storage disorder caused
      by alpha-L-fucosidase deficiency as a result of FUCA1 gene mutations. Here, we
      studied clinical features and the molecular basis of fucosidosis in a family from
      Iran, including two probands and nine family members. METHODS: DNA sample of two
      probands were screened for gene defects using a next generation sequencing
      technique. The sequencing processes were performed on an Illumina Hiseq 4000
      platform. Sequence reads were analysed using BWA-GATK. RESULTS: Next generation
      sequencing revealed a frameshift mutation caused by 2 bp deletion (c.837_838
      delTG; p.Cys279) in the FUCA1 gene. The identified mutation was tested in all
      participants. Homozygous patients had almost all the complications associated
      with fucosidosis, while heterozygous carriers were unaffected. CONCLUSIONS: The
      variant c.837_838 delTG; p.Cys279 has not been reported previously and is
      predicted to be pathogenic due to a premature stop codon.

PMID- 29588376
TI  - TRRAP is a central regulator of human multiciliated cell formation.
AB  - The multiciliated cell (MCC) is an evolutionarily conserved cell type, which in
      vertebrates functions to promote directional fluid flow across epithelial
      tissues. In the conducting airway, MCCs are generated by basal stem/progenitor
      cells and act in concert with secretory cells to perform mucociliary clearance to
      expel pathogens from the lung. Studies in multiple systems, including Xenopus
      laevis epidermis, murine trachea, and zebrafish kidney, have uncovered a
      transcriptional network that regulates multiple steps of multiciliogenesis,
      ultimately leading to an MCC with hundreds of motile cilia extended from their
      apical surface, which beat in a coordinated fashion. Here, we used a pool-based
      short hairpin RNA screening approach and identified TRRAP, an essential component
      of multiple histone acetyltransferase complexes, as a central regulator of MCC
      formation. Using a combination of immunofluorescence, signaling pathway
      modulation, and genomic approaches, we show that (a) TRRAP acts downstream of the
      Notch2-mediated basal progenitor cell fate decision and upstream of Multicilin to
      control MCC differentiation; and (b) TRRAP binds to the promoters and regulates
      the expression of a network of genes involved in MCC differentiation and
      function, including several genes associated with human ciliopathies.

PMID- 29588377
TI  - Myosin 1b promotes axon formation by regulating actin wave propagation and growth
      cone dynamics.
AB  - Single-headed myosin 1 has been identified in neurons, but its function in these
      cells is still unclear. We demonstrate that depletion of myosin 1b (Myo1b),
      inhibition of its motor activity, or its binding to phosphoinositides impairs the
      formation of the axon, whereas overexpression of Myo1b increases the number of
      axon-like structures. Myo1b is associated with growth cones and actin waves, two
      major contributors to neuronal symmetry breaking. We show that Myo1b controls the
      dynamics of the growth cones and the anterograde propagation of the actin waves.
      By coupling the membrane to the actin cytoskeleton, Myo1b regulates the size of
      the actin network as well as the stability and size of filopodia in the growth
      cones. Our data provide the first evidence that a myosin 1 plays a major role in
      neuronal symmetry breaking and argue for a mechanical control of the actin
      cytoskeleton both in actin waves and in the growth cones by this myosin.

PMID- 29588379
TI  - The Draft Genome of the Invasive Walking Stick, Medauroidea extradendata, Reveals
      Extensive Lineage-Specific Gene Family Expansions of Cell Wall Degrading Enzymes
      in Phasmatodea.
AB  - Plant cell wall components are the most abundant macromolecules on Earth. The
      study of the breakdown of these molecules is thus a central question in biology.
      Surprisingly, plant cell wall breakdown by herbivores is relatively poorly
      understood, as nearly all early work focused on the mechanisms used by symbiotic
      microbes to breakdown plant cell walls in insects such as termites. Recently,
      however, it has been shown that many organisms make endogenous cellulases.
      Insects, and other arthropods, in particular have been shown to express a variety
      of plant cell wall degrading enzymes in many gene families with the ability to
      break down all the major components of the plant cell wall. Here we report the
      genome of a walking stick, Medauroidea extradentata, an obligate herbivore that
      makes uses of endogenously produced plant cell wall degrading enzymes. We present
      a draft of the 3.3Gbp genome along with an official gene set that contains a
      diversity of plant cell wall degrading enzymes. We show that at least one of the
      major families of plant cell wall degrading enzymes, the pectinases, have
      undergone a striking lineage-specific gene family expansion in the Phasmatodea.
      This genome will be a useful resource for comparative evolutionary studies with
      herbivores in many other clades and will help elucidate the mechanisms by which
      metazoans breakdown plant cell wall components.

PMID- 29588378
TI  - ESCRT-III is required for scissioning new peroxisomes from the endoplasmic
      reticulum.
AB  - Dynamic control of peroxisome proliferation is integral to the peroxisome's many
      functions. The endoplasmic reticulum (ER) serves as a source of preperoxisomal
      vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis
      and support growth and division of existing peroxisomes. However, the mechanism
      of PPV formation and release from the ER remains poorly understood. In this
      study, we show that endosomal sorting complexes required for transport (ESCRT)
      III are required to release PPVs budding from the ER into the cytosol. Absence of
      ESCRT-III proteins impedes de novo peroxisome formation and results in an
      aberrant peroxisome population in vivo. Using a cell-free PPV budding assay, we
      show that ESCRT-III proteins Vps20 and Snf7 are necessary to release PPVs from
      the ER. ESCRT-III is therefore a positive effector of membrane scission for
      vesicles budding both away from and toward the cytosol. These findings have
      important implications for the evolutionary timing of emergence of peroxisomes
      and the rest of the internal membrane architecture of the eukaryotic cell.

PMID- 29588380
TI  - QTL Mapping of Genome Regions Controlling Manganese Uptake in Lentil Seed.
AB  - This study evaluated Mn concentration in the seeds of 120 RILs of lentil
      developed from the cross "CDC Redberry" * "ILL7502". Micronutrient analysis using
      atomic absorption spectrometry indicated mean seed manganese (Mn) concentrations
      ranging from 8.5 to 26.8 mg/kg, based on replicated field trials grown at three
      locations in Turkey in 2012 and 2013. A linkage map of lentil was constructed and
      consisted of seven linkage groups with 5,385 DNA markers. The total map length
      was 973.1 cM, with an average distance between markers of 0.18 cM. A total of 6
      QTL for Mn concentration were identified using composite interval mapping (CIM).
      All QTL were statistically significant and explained 15.3-24.1% of the phenotypic
      variation, with LOD scores ranging from 3.00 to 4.42. The high-density genetic
      map reported in this study will increase fundamental knowledge of the genome
      structure of lentil, and will be the basis for the development of micronutrient
      enriched lentil genotypes to support biofortification efforts.

PMID- 29588381
TI  - A Bayesian Genomic Regression Model with Skew Normal Random Errors.
AB  - Genomic selection (GS) has become a tool for selecting candidates in plant and
      animal breeding programs. In the case of quantitative traits, it is common to
      assume that the distribution of the response variable can be approximated by a
      normal distribution. However, it is known that the selection process leads to
      skewed distributions. There is vast statistical literature on skewed
      distributions, but the skew normal distribution is of particular interest in this
      research. This distribution includes a third parameter that drives the skewness,
      so that it generalizes the normal distribution. We propose an extension of the
      Bayesian whole-genome regression to skew normal distribution data in the context
      of GS applications, where usually the number of predictors vastly exceeds the
      sample size. However, it can also be applied when the number of predictors is
      smaller than the sample size. We used a stochastic representation of a skew
      normal random variable, which allows the implementation of standard Markov Chain
      Monte Carlo (MCMC) techniques to efficiently fit the proposed model. The
      predictive ability and goodness of fit of the proposed model were evaluated using
      simulated and real data, and the results were compared to those obtained by the
      Bayesian Ridge Regression model. Results indicate that the proposed model has a
      better fit and is as good as the conventional Bayesian Ridge Regression model for
      prediction, based on the DIC criterion and cross-validation, respectively. A
      computing program coded in the R statistical package and C programming language
      to fit the proposed model is available as supplementary material.

PMID- 29588382
TI  - Distinguishing Among Evolutionary Forces Acting on Genome-Wide Base Composition:
      Computer Simulation Analysis of Approximate Methods for Inferring Site Frequency
      Spectra of Derived Mutations.
AB  - Inferred ancestral nucleotide states are increasingly employed in analyses of
      within- and between -species genome variation. Although numerous studies have
      focused on ancestral inference among distantly related lineages, approaches to
      infer ancestral states in polymorphism data have received less attention.
      Recently developed approaches that employ complex transition matrices allow us to
      infer ancestral nucleotide sequence in various evolutionary scenarios of base
      composition. However, the requirement of a single gene tree to calculate a
      likelihood is an important limitation for conducting ancestral inference using
      within-species variation in recombining genomes. To resolve this problem, and to
      extend the applicability of ancestral inference in studies of base composition
      evolution, we first evaluate three previously proposed methods to infer ancestral
      nucleotide sequences among within- and between-species sequence variation data.
      The methods employ a single allele, bifurcating tree, or a star tree for within
      species variation data. Using simulated nucleotide sequences, we employ ancestral
      inference to infer fixations and polymorphisms. We find that all three methods
      show biased inference. We modify the bifurcating tree method to include weights
      to adjust for an expected site frequency spectrum, "bifurcating tree with
      weighting" (BTW). Our simulation analysis show that the BTW method can
      substantially improve the reliability and robustness of ancestral inference in a
      range of scenarios that include non-neutral and/or non-stationary base
      composition evolution.

PMID- 29588383
TI  - A neurological letter from Zimbabwe.

PMID- 29588384
TI  - Autoimmune encephalitis (NMDAR antibody) in a patient receiving chronic post
      transplant immunosuppression.
AB  - Autoimmune encephalitis associated with antibodies (Abs) directed against the
      synaptic ligand-gated ion channel NMDA receptor (NMDAR) was first described as a
      paraneoplastic disorder in association with ovarian teratoma. Other forms of
      neoplasia have subsequently been reported although many patients do not have a
      tumour. Tumour removal, where applicable, and immunotherapy form the mainstays of
      treatment. We present a patient who developed NMDAR-Ab encephalitis despite being
      chronically immunosuppressed following organ transplantation, and who was
      eventually found to have an occult malignancy in the form of non-Hodgkin's
      lymphoma.

PMID- 29588385
TI  - Non-vesicular lipid trafficking at the endoplasmic reticulum-mitochondria
      interface.
AB  - Mitochondria are highly dynamic organelles involved in various cellular processes
      such as energy production, regulation of calcium homeostasis, lipid trafficking,
      and apoptosis. To fulfill all these functions and preserve their morphology and
      dynamic behavior, mitochondria need to maintain a defined protein and lipid
      composition in both their membranes. The maintenance of mitochondrial membrane
      identity requires a selective and regulated transport of specific lipids from/to
      the endoplasmic reticulum (ER) and across the mitochondria outer and inner
      membranes. Since they are not integrated in the classical vesicular trafficking
      routes, mitochondria exchange lipids with the ER at sites of close apposition
      called membrane contact sites. Deregulation of such transport activities results
      in several pathologies including cancer and neurodegenerative disorders. However,
      we are just starting to understand the function of ER-mitochondria contact sites
      in lipid transport, what are the proteins involved and how they are regulated. In
      this review, we summarize recent insights into lipid transport pathways at the ER
      mitochondria interface and discuss the implication of recently identified lipid
      transfer proteins in these processes.

PMID- 29588386
TI  - Probing ubiquitin and SUMO conjugation and deconjugation.
AB  - Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins including small Ubl modifier
      (SUMO) are small proteins which are covalently linked to target proteins to
      regulate their functions. In this review, we discuss the current state of the art
      and point out what we feel this field urgently needs in order to delineate the
      wiring of the system. We discuss what is needed to unravel the connections
      between different components of the conjugation machineries for ubiquitylation
      and SUMOylation, and to unravel the connections between the conjugation
      machineries and their substrates. Chemical probes are key tools to probe signal
      transduction by these small proteins that may help understand their action. This
      rapidly moving field has resulted in various small molecules that will help us to
      further understand Ub and SUMO function and that may lead to the development of
      new drugs.

PMID- 29588387
TI  - Constraint-based modeling in microbial food biotechnology.
AB  - Genome-scale metabolic network reconstruction offers a means to leverage the
      value of the exponentially growing genomics data and integrate it with other
      biological knowledge in a structured format. Constraint-based modeling (CBM)
      enables both the qualitative and quantitative analyses of the reconstructed
      networks. The rapid advancements in these areas can benefit both the industrial
      production of microbial food cultures and their application in food processing.
      CBM provides several avenues for improving our mechanistic understanding of
      physiology and genotype-phenotype relationships. This is essential for the
      rational improvement of industrial strains, which can further be facilitated
      through various model-guided strain design approaches. CBM of microbial
      communities offers a valuable tool for the rational design of defined food
      cultures, where it can catalyze hypothesis generation and provide unintuitive
      rationales for the development of enhanced community phenotypes and,
      consequently, novel or improved food products. In the industrial-scale production
      of microorganisms for food cultures, CBM may enable a knowledge-driven bioprocess
      optimization by rationally identifying strategies for growth and stability
      improvement. Through these applications, we believe that CBM can become a
      powerful tool for guiding the areas of strain development, culture development
      and process optimization in the production of food cultures. Nevertheless, in
      order to make the correct choice of the modeling framework for a particular
      application and to interpret model predictions in a biologically meaningful
      manner, one should be aware of the current limitations of CBM.

PMID- 29588388
TI  - SUMOylome Profiling Reveals a Diverse Array of Nuclear Targets Modified by the
      SUMO Ligase SIZ1 during Heat Stress.
AB  - The posttranslational addition of small ubiquitin-like modifier (SUMO) is an
      essential protein modification in plants that provides protection against
      numerous environmental challenges. Ligation is accomplished by a small set of
      SUMO ligases, with the SAP-MIZ domain-containing SIZ1 and METHYL METHANESULFONATE
      SENSITIVE21 (MMS21) ligases having critical roles in stress protection and DNA
      endoreduplication/repair, respectively. To help identify their corresponding
      targets in Arabidopsis thaliana, we used siz1 and mms21 mutants for proteomic
      analyses of SUMOylated proteins enriched via an engineered SUMO1 isoform suitable
      for mass spectrometric studies. Through multiple data sets from seedlings grown
      at normal temperatures or exposed to heat stress, we identified over 1000 SUMO
      targets, most of which are nuclear localized. Whereas no targets could be
      assigned to MMS21, suggesting that it modifies only a few low abundance proteins,
      numerous targets could be assigned to SIZ1, including major transcription
      factors, coactivators/repressors, and chromatin modifiers connected to abiotic
      and biotic stress defense, some of which associate into multisubunit regulatory
      complexes. SIZ1 itself is also a target, but studies with mutants protected from
      SUMOylation failed to uncover a regulatory role. The catalog of SIZ1 substrates
      indicates that SUMOylation by this ligase provides stress protection by modifying
      a large array of key nuclear regulators.

PMID- 29588389
TI  - GRAIN SIZE AND NUMBER1 Negatively Regulates the OsMKKK10-OsMKK4-OsMPK6 Cascade to
      Coordinate the Trade-off between Grain Number per Panicle and Grain Size in Rice.
AB  - Grain number and size are interactive agronomic traits that determine grain
      yield. However, the molecular mechanisms responsible for coordinating the trade
      off between these traits remain elusive. Here, we characterized the rice (Oryza
      sativa) grain size and number1 (gsn1) mutant, which has larger grains but sparser
      panicles than the wild type due to disordered localized cell differentiation and
      proliferation. GSN1 encodes the mitogen-activated protein kinase phosphatase
      OsMKP1, a dual-specificity phosphatase of unknown function. Reduced expression of
      GSN1 resulted in larger and fewer grains, whereas increased expression resulted
      in more grains but reduced grain size. GSN1 directly interacts with and
      inactivates the mitogen-activated protein kinase OsMPK6 via dephosphorylation.
      Consistent with this finding, the suppression of mitogen-activated protein kinase
      genes OsMPK6, OsMKK4, and OsMKKK10 separately resulted in denser panicles and
      smaller grains, which rescued the mutant gsn1 phenotypes. Therefore, OsMKKK10
      OsMKK4-OsMPK6 participates in panicle morphogenesis and acts on a common pathway
      in rice. We confirmed that GSN1 is a negative regulator of the OsMKKK10-OsMKK4
      OsMPK6 cascade that determines panicle architecture. The GSN1-MAPK module
      coordinates the trade-off between grain number and grain size by integrating
      localized cell differentiation and proliferation. These findings provide
      important insights into the developmental plasticity of the panicle and a
      potential means to improve crop yields.

PMID- 29588391
TI  - Evaluating receipt of and inability to discontinue tobacco industry direct mail.

PMID- 29588392
TI  - Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pre- and Posttreatment
      Breast Cancers in the SWOG S0800 Phase II Neoadjuvant Chemotherapy Trial.
AB  - Our aim was to examine the association of pretreatment tumor-infiltrating
      lymphocyte (TIL) count and PD-L1 levels with pathologic complete response (pCR)
      and assess immune marker changes following treatment in tumor specimens from the
      S0800 clinical trial, which randomized patients to bevacizumab + nab-paclitaxel,
      followed by doxorubicin/cyclophosphamide (AC) versus two control arms without
      bevacizumab (varying sequence of AC and nab-paclitaxel). TILs were assessed in
      124 pre- and 62 posttreatment tissues (including 59 pairs). PD-L1 was assessed in
      120 pre- and 43 posttreatment tissues (including 39 pairs) using the 22C3
      antibody. Baseline and treatment-induced immune changes were correlated with pCR
      and survival using estrogen receptor (ER) and treatment-adjusted logistic and Cox
      regressions, respectively. At baseline, the mean TIL count was 17.4% (17% had
      zero TILs, 9% had >=50% TILs). Posttreatment, mean TIL count decreased to 11% (5%
      had no TILs, 2% had >50% TILs). In paired samples, the mean TIL change was 15%
      decrease. Baseline PD-L1 was detected in 43% of cases (n = 5 in tumor cells, n =
      29 stroma, n = 18 tumor + stroma). Posttreatment, PD-L1 expression was not
      significantly lower (33%). Higher baseline TIL count and PD-L1 positivity rate
      were associated with higher pCR rate even after adjustment for treatment and ER
      status (P = 0.018). There was no association between TIL counts, PD-L1
      expression, and survival due to few events. In conclusion, TIL counts, but not PD
      L1 expression, decreased significantly after treatment. Continued PD-L1
      expression in some residual cancers raises the possibility that adjuvant immune
      checkpoint inhibitor therapy could improve survival in this patient population.
      Mol Cancer Ther; 17(6); 1324-31. (c)2018 AACR.

PMID- 29588390
TI  - TANDEM ZINC-FINGER/PLUS3 Is a Key Component of Phytochrome A Signaling.
AB  - Phytochrome A (phyA) is the primary plant photoreceptor responsible for
      perceiving and mediating various responses to far-red (FR) light and is essential
      for survival in canopy shade. In this study, we identified two Arabidopsis
      thaliana mutants that grew longer hypocotyls in FR light. Genetic analyses showed
      that they were allelic and their FR phenotypes were caused by mutations in the
      gene named TANDEM ZINC-FINGER/PLUS3 (TZP), previously shown to encode a nuclear
      protein involved in blue light signaling and phyB-dependent regulation of
      photoperiodic flowering. We show that the expression of TZP is dramatically
      induced by light and that TZP proteins are differentially modified in different
      light conditions. Furthermore, we show that TZP interacts with both phyA and FAR
      RED ELONGATED HYPOCOTYL1 (FHY1) and regulates the abundance of phyA, FHY1, and
      ELONGATED HYPOCOTYL5 proteins in FR light. Moreover, our data indicate that TZP
      is required for the formation of a phosphorylated form of phyA in the nucleus in
      FR light. Together, our results identify TZP as a positive regulator of phyA
      signaling required for phosphorylation of the phyA photoreceptor, thus suggesting
      an important role of phosphorylated phyA in inducing the FR light response.

PMID- 29588393
TI  - IMGN779, a Novel CD33-Targeting Antibody-Drug Conjugate with DNA-Alkylating
      Activity, Exhibits Potent Antitumor Activity in Models of AML.
AB  - The myeloid differentiation antigen CD33 has long been exploited as a target for
      antibody-based therapeutic approaches in acute myeloid leukemia (AML). Validation
      of this strategy was provided with the approval of the CD33-targeting antibody
      drug conjugate (ADC) gemtuzumab ozogamicin in 2000; the clinical utility of this
      agent, however, has been hampered by safety concerns. Thus, the full potential of
      CD33-directed therapy in AML remains to be realized, and considerable interest
      exists in the design and development of more effective ADCs that confer high
      therapeutic indices and favorable tolerability profiles. Here, we describe the
      preclinical characterization of a novel CD33-targeting ADC, IMGN779, which
      utilizes a unique DNA-alkylating payload to achieve potent antitumor effects with
      good tolerability. The payload, DGN462, is prototypical of a novel class of
      purpose-created indolinobenzodiazeprine pseudodimers, termed IGNs. With low
      picomolar potency, IMGN779 reduced viability in a panel of AML cell lines in
      vitro Mechanistically, the cytotoxic activity of IMGN779 involved DNA damage,
      cell-cycle arrest, and apoptosis consistent with the mode of action of DGN462.
      Moreover, IMGN779 was highly active against patient-derived AML cells, including
      those with adverse molecular abnormalities, and sensitivity correlated to CD33
      expression levels. In vivo, IMGN779 displayed robust antitumor efficacy in
      multiple AML xenograft and disseminated disease models, as evidenced by durable
      tumor regressions and prolonged survival. Taken together, these findings identify
      IMGN779 as a promising new candidate for evaluation as a novel therapeutic in
      AML. Mol Cancer Ther; 17(6); 1271-9. (c)2018 AACR.

PMID- 29588394
TI  - The phospholipase A2 pathway controls a synaptic cholesterol ester cycle and
      synapse damage.
AB  - The cellular prion protein (PrPC) acts as a scaffold protein that organises
      signalling complexes. In synaptosomes, the aggregation of PrPC by amyloid-beta
      (Abeta) oligomers attracts and activates cytoplasmic phospholipase A2 (cPLA2),
      leading to synapse degeneration. The signalling platform is dependent on
      cholesterol released from cholesterol esters by cholesterol ester hydrolases
      (CEHs). The activation of cPLA2 requires cholesterol released from cholesterol
      esters by cholesterol ester hydrolases (CEHs), enzymes dependent upon platelet
      activating factor (PAF) released by activated cPLA2 This demonstrates a positive
      feedback system in which activated cPLA2 increased cholesterol concentrations,
      which in turn facilitated cPLA2 activation. PAF was also required for the
      incorporation of the tyrosine kinase Fyn and cyclooxygenase (COX)-2 into Abeta
      PrPC-cPLA2 complexes. As a failure to deactivate signalling complexes can lead to
      pathology, the mechanisms involved in their dispersal were studied. PAF
      facilitated the incorporation of acyl-coenzyme A:cholesterol acyltransferase
      (ACAT)-1 into Abeta-PrPC-cPLA2-COX-2-Fyn complexes. The esterification of
      cholesterol reduced cholesterol concentrations, causing dispersal of Abeta-PrPC
      cPLA2-COX-2-Fyn complexes and the cessation of signalling. This study identifies
      PAF as a key mediator regulating the cholesterol ester cycle, activation of cPLA2
      and COX-2 within synapses, and synapse damage.

PMID- 29588395
TI  - Substratum stiffness tunes proliferation downstream of Wnt3a in part by
      regulating integrin-linked kinase and frizzled-1.
AB  - The Wnt/beta-catenin pathway controls a variety of cellular behaviors, aberrant
      activation of which are associated with tumor progression in several types of
      cancer. The same cellular behaviors are also affected by the mechanical
      properties of the extracellular matrix (ECM) substratum, which induces signaling
      through integrins and integrin-linked kinase (ILK). Here, we examined the role of
      substratum stiffness in the regulation of cell proliferation downstream of Wnt3a.
      We found that treatment with Wnt3a increased proliferation of cells cultured on
      stiff substrata, with compliances characteristic of breast tumors, but not of
      cells on soft substrata, with compliances comparable to that of normal mammary
      tissue. Depleting ILK rendered cells unresponsive to Wnt3a on both substrata.
      Ectopic expression of ILK permitted Wnt3a to induce proliferation of cells on
      both microenvironments, although proliferation on soft substrata remained lower
      than that on stiff substrata. We further showed that ILK regulates expression of
      the Wnt receptor frizzled-1 (Fzd1), suggesting the presence of a positive
      feedback loop between Wnt3a, ILK and Fzd1. These findings suggest that tissue
      mechanics regulates the cellular response to Wnt under physiological and
      pathological microenvironmental conditions.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29588396
TI  - Citron kinase-dependent F-actin maintenance at midbody secondary ingression sites
      mediates abscission.
AB  - Abscission is the final step of cytokinesis whereby the intercellular bridge
      (ICB) linking the two daughter cells is cut. The ICB contains a structure called
      the midbody, required for the recruitment and organization of the abscission
      machinery. Final midbody severing is mediated by formation of secondary midbody
      ingression sites, where the ESCRT III component CHMP4B is recruited to mediate
      membrane fusion. It is presently unknown how cytoskeletal elements cooperate with
      CHMP4B to mediate abscission. Here, we show that F-actin is associated with
      midbody secondary sites and is necessary for abscission. F-actin localization at
      secondary sites depends on the activity of RhoA and on the abscission regulator
      citron kinase (CITK). CITK depletion accelerates loss of F-actin proteins at the
      midbody and subsequent cytokinesis defects are reversed by restoring actin
      polymerization. Conversely, midbody hyperstabilization produced by overexpression
      of CITK and ANLN is reversed by actin depolymerization. CITK is required for
      localization of F-actin and ANLN at the abscission sites, as well as for CHMP4B
      recruitment. These results indicate that control of actin dynamics downstream of
      CITK prepares the abscission site for the final cut.

PMID- 29588397
TI  - Loss of PTEN promotes formation of signaling-capable clathrin-coated pits.
AB  - Defective endocytosis and vesicular trafficking of signaling receptors has
      recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated
      pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where
      they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite
      the large number of cargo molecules that traffic through CCPs, it is not well
      understood whether signaling receptors activated in cancer, such as epidermal
      growth factor receptor (EGFR), are regulated through a specific subset of CCPs.
      The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3],
      which is dephosphorylated by phosphatase and tensin homolog (PTEN), is a potent
      tumorigenic signaling lipid. By using total internal reflection fluorescence
      microscopy and automated tracking and detection of CCPs, we found that EGF-bound
      EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that
      correspond with clathrin-dependent EGF-induced signaling. We demonstrated that
      PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased
      PI(3,4,5)P3 resulted in higher proportion of short-lived CCPs, an effect that
      recapitulates PTEN deletion. Altogether, our findings provide evidence for the
      existence of short-lived 'signaling-capable' CCPs.

PMID- 29588398
TI  - The Light Chain Defines the Duration of Action of Botulinum Toxin Serotype A
      Subtypes.
AB  - Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used
      pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa
      protein toxins organized into heavy chain (HC) and light chain (LC) domains
      linked by a disulfide bond. The HC selectively binds to neurons and aids cell
      entry of the enzymatically active LC. There are seven immunological BoNT
      serotypes (A to G); each serotype includes genetic variants, termed subtypes.
      Only two subtypes, BoNT/A1 and BoNT/B1, are currently used as therapeutics. BoNT
      serotype A (BoNT/A) subtypes A2 to A8 show distinct potency, duration of action,
      and pathology relative to BoNT/A1. Specifically, BoNT/A3 possesses shorter
      duration of action and elicits distinct symptoms in mice at high toxin doses. In
      this report, we analyzed the roles of LC and HC of BoNT/A3 for duration of
      action, neuronal cell entry, and mouse pathology by using clostridium-derived
      recombinant hybrid BoNTs consisting of reciprocal LC and HC (BoNTA1/A3 and
      BoNTA3/A1). Hybrid toxins were processed in their expression host to a dichain
      BoNT consisting of LC and HC linked via a disulfide bond. The LC and HC defined
      BoNT potency in mice and BoNT toxicity for cultured neuronal cells, while the LC
      defined the duration of BoNT action in cell and mouse models. Protein alignment
      identified a previously unrecognized region within the LC subtype A3 (LC/A3)
      relative to the other LC serotype A (LC/A) subtypes (low primary acid homology
      [LPH]) that correlated to intracellular LC localization. This study shows the
      utility of recombinant hybrid BoNTs with new therapeutic potential, while
      remaining sensitive to antitoxins and therapies to native BoNT.IMPORTANCE
      Botulinum neurotoxins are the most potent protein toxins for humans and potential
      bioterrorism threats, but they are also widely used as pharmaceuticals. Within
      the large family of BoNTs, only two subtypes are currently used as
      pharmaceuticals, with a large number of BoNT subtypes remaining as untapped
      potential sources for unique pharmaceuticals. Here, two recombinant hybrid toxins
      were engineered, consisting of domains from two BoNT subtypes that possess
      distinct duration of action and activity in human neurons and mice. We define the
      functional domains responsible for BoNT action and demonstrate creation of
      functional hybrid BoNTs with new therapeutic potential, while remaining sensitive
      to antitoxins and therapies to native BoNT.

PMID- 29588399
TI  - Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced
      Resistance to Host Antimicrobials.
AB  - Pseudomonas aeruginosa causes chronic pulmonary infections in patients with
      cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction
      of the exopolysaccharide alginate, correlates with accelerated decline in CF
      patient lung function. Recalcitrance of the mucoid phenotype to clearance by
      antibiotics and the immune response is well documented. However, despite
      advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid
      phenotype both in vitro and in vivo Mixed populations of mucoid isolates and
      nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit
      for coexistence of these variants. In this study, cocultures of mucoid and
      nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL
      37, a cationic antimicrobial peptide, and hydrogen peroxide (H2O2). Alginate
      production by mucoid isolates protected nonmucoid variants in consortia from LL
      37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37
      killing. Conversely, nonmucoid revertants shielded mucoid variants from H2O2
      stress via catalase (KatA) production, which was transcriptionally repressed by
      AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore,
      extracellular release of KatA by nonmucoid revertants was dependent on lys,
      encoding an endolysin implicated in autolysis and extracellular DNA (eDNA)
      release. Overall, these data provide a rationale to study interactions of P.
      aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate
      immunity and persistence within the CF lung.IMPORTANCEP. aeruginosa mucoid
      conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic
      infection and predictive of poor prognosis. The selective benefit of mixed
      populations of mucoid and nonmucoid variants, often isolated from chronically
      infected CF patients, has not been explored. Here, we show that mixed-variant
      communities of P. aeruginosa demonstrate advantages in evasion of innate
      antimicrobials via production of shared goods: alginate and catalase. These data
      argue for therapeutically targeting multiple constituents (both mucoid and
      nonmucoid variants) within diversified P. aeruginosa communities in vivo, as
      these variants can differentially shield one another from components of the host
      response.

PMID- 29588400
TI  - HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface
      Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain.
AB  - Once HIV-1 enters a cell, the viral core is uncoated by a poorly understood
      mechanism and the HIV-1 genomic RNA is reverse transcribed into DNA. Host cell
      factors are essential for these processes, although very few reverse
      transcription complex binding host cell factors have been convincingly shown to
      affect uncoating or reverse transcription. We previously reported that cellular
      eukaryotic translation elongation factor 1A (eEF1A) interacts tightly and
      directly with HIV-1 reverse transcriptase (RT) for more efficient reverse
      transcription. Here we report that the surface-exposed acidic residues in the HIV
      1 RT thumb domain alpha-J helix and flanking regions are important for
      interaction with eEF1A. Mutation of surface-exposed acidic thumb domain residues
      D250, E297, E298, and E300 to arginine resulted in various levels of impairment
      of the interaction between RT and eEF1A. This indicates that this negatively
      charged region in the RT thumb domain is important for interaction with the
      positively charged eEF1A protein. The impairment of RT and eEF1A interaction by
      the RT mutations correlated with the efficiency of reverse transcription,
      uncoating, and infectivity. The best example of this is the strictly conserved
      E300 residue, where mutation significantly impaired the interaction of RT with
      eEF1A and virus replication in CD4+ T cells without affecting in vitro RT
      catalytic activity, RT heterodimerization, or RNase H activity. This study
      demonstrated that the interaction between surface-exposed acidic residues of the
      RT thumb domain and eEF1A is important for HIV-1 uncoating, reverse
      transcription, and replication.IMPORTANCE HIV-1, like all viruses, requires host
      cell proteins for its replication. Understanding the mechanisms behind virus-host
      interactions can lay the foundation for future novel therapeutic developments.
      Our lab has identified eEF1A as a key HIV-1 RT binding host protein that is
      important for the reverse transcription of HIV-1 genomic RNA into DNA. Here we
      identify the first surface-exposed RT residues that underpin interactions with
      eEF1A. Mutation of one strictly conserved RT residue (E300R) delayed reverse
      transcription and viral core uncoating and strongly inhibited HIV-1 replication
      in CD4+ T cells. This study advances the structural and mechanistic detail of the
      key RT-eEF1A interaction in HIV-1 infection and indicates its importance in
      uncoating for the first time. This provides a further basis for the development
      of an RT-eEF1A interaction-inhibiting anti-HIV-1 drug and suggests that the
      surface-exposed acidic patch of the RT thumb domain may be an attractive drug
      target.

PMID- 29588401
TI  - Allometry and Ecology of the Bilaterian Gut Microbiome.
AB  - Classical ecology provides principles for construction and function of biological
      communities, but to what extent these apply to the animal-associated microbiota
      is just beginning to be assessed. Here, we investigated the influence of several
      well-known ecological principles on animal-associated microbiota by
      characterizing gut microbial specimens from bilaterally symmetrical animals
      (Bilateria) ranging from flies to whales. A rigorously vetted sample set
      containing 265 specimens from 64 species was assembled. Bacterial lineages were
      characterized by 16S rRNA gene sequencing. Previously published samples were also
      compared, allowing analysis of over 1,098 samples in total. A restricted number
      of bacterial phyla was found to account for the great majority of gut colonists.
      Gut microbial composition was associated with host phylogeny and diet. We
      identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply
      from previously studied taxa, identifying opportunities to discover new bacterial
      types. The number of bacterial lineages per gut sample was positively associated
      with animal mass, paralleling known species-area relationships from island
      biogeography and implicating body size as a determinant of community stability
      and niche complexity. Samples from larger animals harbored greater numbers of
      anaerobic communities, specifying a mechanism for generating more-complex
      microbial environments. Predictions for species/abundance relationships from
      models of neutral colonization did not match the data set, pointing to
      alternative mechanisms such as selection of specific colonists by environmental
      niche. Taken together, the data suggest that niche complexity increases with gut
      size and that niche selection forces dominate gut community
      construction.IMPORTANCE The intestinal microbiome of animals is essential for
      health, contributing to digestion of foods, proper immune development, inhibition
      of pathogen colonization, and catabolism of xenobiotic compounds. How these
      communities assemble and persist is just beginning to be investigated. Here we
      interrogated a set of gut samples from a wide range of animals to investigate the
      roles of selection and random processes in microbial community construction. We
      show that the numbers of bacterial species increased with the weight of host
      organisms, paralleling findings from studies of island biogeography. Communities
      in larger organisms tended to be more anaerobic, suggesting one mechanism for
      niche diversification. Nonselective processes enable specific predictions for
      community structure, but our samples did not match the predictions of the neutral
      model. Thus, these findings highlight the importance of niche selection in
      community construction and suggest mechanisms of niche diversification.

PMID- 29588402
TI  - Cyclic di-AMP Acts as an Extracellular Signal That Impacts Bacillus subtilis
      Biofilm Formation and Plant Attachment.
AB  - There is a growing appreciation for the impact that bacteria have on higher
      organisms. Plant roots often harbor beneficial microbes, such as the Gram
      positive rhizobacterium Bacillus subtilis, that influence their growth and
      susceptibility to disease. The ability to form surface-attached microbial
      communities called biofilms is crucial for the ability of B. subtilis to adhere
      to and protect plant roots. In this study, strains harboring deletions of the B.
      subtilis genes known to synthesize and degrade the second messenger cyclic di
      adenylate monophosphate (c-di-AMP) were examined for their involvement in biofilm
      formation and plant attachment. We found that intracellular production of c-di
      AMP impacts colony biofilm architecture, biofilm gene expression, and plant
      attachment in B. subtilis We also show that B. subtilis secretes c-di-AMP and
      that putative c-di-AMP transporters impact biofilm formation and plant root
      colonization. Taken together, our data describe a new role for c-di-AMP as a
      chemical signal that affects important cellular processes in the environmentally
      and agriculturally important soil bacterium B. subtilis These results suggest
      that the "intracellular" signaling molecule c-di-AMP may also play a previously
      unappreciated role in interbacterial cell-cell communication within plant
      microbiomes.IMPORTANCE Plants harbor bacterial communities on their roots that
      can significantly impact their growth and pathogen resistance. In most cases,
      however, the signals that mediate host-microbe and microbe-microbe interactions
      within these communities are unknown. A detailed understanding of these
      interaction mechanisms could facilitate the manipulation of these communities for
      agricultural or environmental purposes. Bacillus subtilis is a plant-growth
      promoting bacterium that adheres to roots by forming biofilms. We therefore began
      by exploring signals that might impact its biofilm formation. We found that B.
      subtilis secretes c-di-AMP and that the ability to produce, degrade, or transport
      cyclic di-adenylate monophosphate (c-di-AMP; a common bacterial second messenger)
      affects B. subtilis biofilm gene expression and plant attachment. To our
      knowledge, this is the first demonstration of c-di-AMP impacting a mutualist host
      microbe association and suggests that c-di-AMP may function as a previously
      unappreciated extracellular signal able to mediate interactions within plant
      microbiomes.

PMID- 29588403
TI  - Exogenous Stimulation of Type I Interferon Protects Mice with Chronic
      Granulomatous Disease from Aspergillosis through Early Recruitment of Host
      Protective Neutrophils into the Lung.
AB  - Invasive aspergillosis (IA) remains the primary cause of morbidity and mortality
      in chronic granulomatous disease (CGD) patients, often due to infection by
      Aspergillus species refractory to antifungals. This motivates the search for
      alternative treatments, including immunotherapy. We investigated the effect of
      exogenous type I interferon (IFN) activation on the outcome of IA caused by three
      Aspergillus species, A. fumigatus, A. nidulans, and A. tanneri, in CGD mice. The
      animals were treated with poly(I):poly(C) carboxymethyl cellulose poly-l-lysine
      (PICLC), a mimetic of double-stranded RNA, 24 h preinfection and postinfection.
      The survival rates and lung fungal burdens were markedly improved by PICLC
      immunotherapy in animals infected with any one of the three Aspergillus species.
      While protection from IA was remarkable, PICLC induction of type I IFN in the
      lungs surged 24 h posttreatment and returned to baseline levels by 48 h,
      suggesting that PICLC altered early events in protection against IA.
      Immunophenotyping of recruited leukocytes and histopathological examination of
      tissue sections showed that PICLC induced similar cellular infiltrates as those
      in untreated-infected mice, in both cases dominated by monocytic cells and
      neutrophils. However, the PICLC immunotherapy resulted in a marked earlier
      recruitment of the leukocytes. Unlike with conidia, infection with A. nidulans
      germlings reduced the protective effect of PICLC immunotherapy. Additionally,
      antibody depletion of neutrophils totally reversed the protection, suggesting
      that neutrophils are crucial for PICLC-mediated protection. Together, these data
      show that prophylactic PICLC immunotherapy prerecruits these cells, enabling them
      to attack the conidia and thus resulting in a profound protection from
      IA.IMPORTANCE Patients with chronic granulomatous disease (CGD) are highly
      susceptible to invasive aspergillosis (IA). While Aspergillus fumigatus is the
      most-studied Aspergillus species, CGD patients often suffer IA caused by A.
      nidulans, A. tanneri, and other rare species. These non-fumigatus Aspergillus
      species are more resistant to antifungal drugs and cause higher fatality rates
      than A. fumigatus Therefore, alternative therapies are needed to protect CGD
      patients. We report an effective immunotherapy of mice infected with three
      Aspergillus species via PICLC dosing. While protection from IA was long lasting,
      PICLC induction of type I IFN surged but quickly returned to baseline levels,
      suggesting that PICLC was altering early events in IA. Interestingly, we found
      responding immune cells to be similar between PICLC-treated and untreated
      infected mice. However, PICLC immunotherapy resulted in an earlier recruitment of
      the leukocytes and suppressed fungal growth. This study highlights the value of
      type I IFN induction in CGD patients.

PMID- 29588404
TI  - The Typhoid Toxin Produced by the Nontyphoidal Salmonella enterica Serotype
      Javiana Is Required for Induction of a DNA Damage Response In Vitro and Systemic
      Spread In Vivo.
AB  - The Salmonella cytolethal distending toxin (S-CDT), first described as the
      "typhoid toxin" in Salmonella enterica subsp. enterica serotype Typhi, induces
      DNA damage in eukaryotic cells. Recent studies have shown that more than 40
      nontyphoidal Salmonella (NTS) serotypes carry genes that encode S-CDT, yet very
      little is known about the activity, function, and role of S-CDT in NTS. Here we
      show that deletion of genes encoding the binding subunit (pltB) and a
      bacteriophage muramidase predicted to play a role in toxin export (ttsA) does not
      abolish toxin activity in the S-CDT-positive NTS Salmonella enterica subsp.
      enterica serotype Javiana. However, S. Javiana strains harboring deletions of
      both pltB and its homolog artB, had a complete loss of S-CDT activity, suggesting
      that S. Javiana carries genes encoding two variants of the binding subunit. S-CDT
      mediated DNA damage, as determined by phosphorylation of histone 2AX (H2AX),
      producing phosphorylated H2AX (gammaH2AX), was restricted to epithelial cells in
      S and G2/M phases of the cell cycle and did not result in apoptosis or cell
      death. Compared to mice infected with a DeltacdtB strain, mice infected with wild
      type S. Javiana had significantly higher levels of S. Javiana in the liver, but
      not in the spleen, ileum, or cecum. Overall, we show that production of active S
      CDT by NTS serotype S. Javiana requires different genes (cdtB, pltA, and either
      pltB or artB) for expression of biologically active toxin than those reported for
      S-CDT production by S. Typhi (cdtB, pltA, pltB, and ttsA). However, as in S.
      Typhi, NTS S-CDT influences the outcome of infection both in vitro and in
      vivoIMPORTANCE Nontyphoidal Salmonella (NTS) are a major cause of bacterial food
      borne illness worldwide; however, our understanding of virulence mechanisms that
      determine the outcome and severity of nontyphoidal salmonellosis is incompletely
      understood. Here we show that S-CDT produced by NTS plays a significant role in
      the outcome of infection both in vitro and in vivo, highlighting S-CDT as an
      important virulence factor for nontyphoidal Salmonella serotypes. Our data also
      contribute novel information about the function of S-CDT, as S-CDT-mediated DNA
      damage occurs only during certain phases of the cell cycle, and the resulting
      damage does not induce cell death as assessed using a propidium iodide exclusion
      assay. Importantly, our data support that, despite having genetically similar S
      CDT operons, NTS serotype S. Javiana has different genetic requirements than S.
      Typhi, for the production and export of active S-CDT.

PMID- 29588406
TI  - Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor
      circinelloides in Innate Granulomas In Vivo.
AB  - Mucormycosis is an emerging fungal infection with extremely high mortality rates
      in patients with defects in their innate immune response, specifically in
      functions mediated through phagocytes. However, we currently have a limited
      understanding of the molecular and cellular interactions between these innate
      immune effectors and mucormycete spores during the early immune response. Here,
      the early events of innate immune recruitment in response to infection by Mucor
      circinelloides spores are modeled by a combined in silico modeling approach and
      real-time in vivo microscopy. Phagocytes are rapidly recruited to the site of
      infection in a zebrafish larval model of mucormycosis. This robust early
      recruitment protects from disease onset in vivoIn silico analysis identified that
      protection is dependent on the number of phagocytes at the infection site, but
      not the speed of recruitment. The mathematical model highlights the role of
      proinflammatory signals for phagocyte recruitment and the importance of
      inhibition of spore germination for protection from active fungal disease. These
      in silico data are supported by an in vivo lack of fungal spore killing and lack
      of reactive oxygen burst, which together result in latent fungal infection.
      During this latent stage of infection, spores are controlled in innate granulomas
      in vivo Disease can be reactivated by immunosuppression. Together, these data
      represent the first in vivo real-time analysis of innate granuloma formation
      during the early stages of a fungal infection. The results highlight a potential
      latent stage during mucormycosis that should urgently be considered for clinical
      management of patients.IMPORTANCE Mucormycosis is a dramatic fungal infection
      frequently leading to the death of patients. We know little about the immune
      response to the fungus causing this infection, although evidence points toward
      defects in early immune events after infection. Here, we dissect this early
      immune response to infectious fungal spores. We show that specialized white blood
      cells (phagocytes) rapidly respond to these spores and accumulate around the
      fungus. However, we demonstrate that the mechanisms that enable phagocytes to
      kill the fungus fail, allowing for survival of spores. Instead a cluster of
      phagocytes resembling an early granuloma is formed around spores to control the
      latent infection. This study is the first detailed analysis of early granuloma
      formation during a fungal infection highlighting a latent stage that needs to be
      considered for clinical management of patients.

PMID- 29588405
TI  - Concurrent Host-Pathogen Transcriptional Responses in a Clostridium perfringens
      Murine Myonecrosis Infection.
AB  - To obtain an insight into host-pathogen interactions in clostridial myonecrosis,
      we carried out comparative transcriptome analysis of both the bacterium and the
      host in a murine Clostridium perfringens infection model, which is the first time
      that such an investigation has been conducted. Analysis of the host transcriptome
      from infected muscle tissues indicated that many genes were upregulated compared
      to the results seen with mock-infected mice. These genes were enriched for host
      defense pathways, including Toll-like receptor (TLR) and Nod-like receptor (NLR)
      signaling components. Real-time PCR confirmed that host TLR2 and NLRP3
      inflammasome genes were induced in response to C. perfringens infection.
      Comparison of the transcriptome of C. perfringens cells from the infected tissues
      with that from broth cultures showed that host selective pressure induced a
      global change in C. perfringens gene expression. A total of 33% (923) of C.
      perfringens genes were differentially regulated, including 10 potential virulence
      genes that were upregulated relative to their expression in vitro These genes
      encoded putative proteins that may be involved in the synthesis of cell wall
      associated macromolecules, in adhesion to host cells, or in protection from host
      cationic antimicrobial peptides. This report presents the first successful
      expression profiling of coregulated transcriptomes of bacterial and host genes
      during a clostridial myonecrosis infection and provides new insights into disease
      pathogenesis and host-pathogen interactions.IMPORTANCEClostridium perfringens is
      the causative agent of traumatic clostridial myonecrosis, or gas gangrene. In
      this study, we carried out transcriptional analysis of both the host and the
      bacterial pathogen in a mouse myonecrosis infection. The results showed that in
      comparison to mock-infected control tissues, muscle tissues from C. perfringens
      infected mice had a significantly altered gene expression profile. In particular,
      the expression of many genes involved in the innate immune system was
      upregulated. Comparison of the expression profiles of C. perfringens cells
      isolated from the infected tissues with those from equivalent broth cultures
      identified many potential virulence genes that were significantly upregulated in
      vivo These studies have provided a new understanding of the range of factors
      involved in host-pathogen interactions in a myonecrosis infection.

PMID- 29588407
TI  - The Sole DEAD-Box RNA Helicase of the Gastric Pathogen Helicobacter pylori Is
      Essential for Colonization.
AB  - Present in every kingdom of life, generally in multiple copies, DEAD-box RNA
      helicases are specialized enzymes that unwind RNA secondary structures. They play
      major roles in mRNA decay, ribosome biogenesis, and adaptation to cold
      temperatures. Most bacteria have multiple DEAD-box helicases that present both
      specialized and partially redundant functions. By using phylogenomics, we
      revealed that the Helicobacter genus, including the major gastric pathogen H.
      pylori, is among the exceptions, as it encodes a sole DEAD-box RNA helicase. In
      H. pylori, this helicase, designated RhpA, forms a minimal RNA degradosome
      together with the essential RNase, RNase J, a major player in the control of RNA
      decay. Here, we used H. pylori as a model organism with a sole DEAD-box helicase
      and investigated the role of this helicase in H. pylori physiology, ribosome
      assembly, and during in vivo colonization. Our data showed that RhpA is
      dispensable for growth at 37 degrees C but crucial at 33 degrees C, suggesting an
      essential role of the helicase in cold adaptation. Moreover, we found that a
      DeltarhpA mutant was impaired in motility and deficient in colonization of the
      mouse model. RhpA is involved in the maturation of 16S rRNA at 37 degrees C and
      is associated with translating ribosomes. At 33 degrees C, RhpA is, in addition,
      recruited to individual ribosomal subunits. Finally, via its role in the RNA
      degradosome, RhpA directs the regulation of the expression of its partner, RNase
      J. RhpA is thus a multifunctional enzyme that, in H. pylori, plays a central role
      in gene regulation and in the control of virulence.IMPORTANCE We present the
      results of our study on the role of RhpA, the sole DEAD-box RNA helicase encoded
      by the major gastric pathogen Helicobacter pylori We observed that all the
      Helicobacter species possess such a sole helicase, in contrast to most free
      living bacteria. RhpA is not essential for growth of H. pylori under normal
      conditions. However, deletion of rhpA leads to a motility defect and to total
      inhibition of the ability of H. pylori to colonize a mouse model. We also
      demonstrated that this helicase encompasses most of the functions of its
      specialized orthologs described so far. We found that RhpA is a key element of
      the bacterial adaptation to colder temperatures and plays a minor role in
      ribosome biogenesis. Finally, RhpA regulates transcription of the rnj gene
      encoding RNase J, its essential partner in the minimal H. pylori RNA degradosome,
      and thus plays a crucial role in the control of RNA decay.

PMID- 29588408
TI  - Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen
      Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs.
AB  - In all eukaryotic kingdoms, mitogen-activated protein kinases (MAPKs) play
      critical roles in cellular responses to environmental cues. These MAPKs are
      activated by phosphorylation at highly conserved threonine and tyrosine residues
      in response to specific inputs, leading to their accumulation in the nucleus and
      the activation of their downstream targets. A specific MAP kinase can regulate
      different downstream targets depending on the nature of the input signal, thereby
      raising a key question: what defines the stress-specific outputs of MAP kinases?
      We find that the Hog1 MAPK contributes to nitrosative-stress resistance in
      Candida albicans even though it displays minimal stress-induced phosphorylation
      under these conditions. We show that Hog1 becomes oxidized in response to
      nitrosative stress, accumulates in the nucleus, and regulates the nitrosative
      stress-induced transcriptome. Mutation of specific cysteine residues revealed
      that C156 and C161 function together to promote stress resistance, Hog1-mediated
      nitrosative-stress-induced gene expression, resistance to phagocytic killing, and
      C. albicans virulence. We propose that the oxidation of Hog1, rather than its
      phosphorylation, contributes to the nitrosative-stress-specific responses of this
      MAP kinase.IMPORTANCE Mitogen-activated protein kinases play key roles in the
      responses of eukaryotic cells to extracellular signals and are critical for
      environmental-stress resistance. The widely accepted paradigm is that MAP kinases
      are activated by phosphorylation, which then triggers their nuclear accumulation
      and the activation of target proteins and genes that promote cellular adaptation.
      Our data suggest that alternative forms of posttranslational modification can
      modulate MAP kinase functionality in Candida albicans We demonstrate that Hog1 is
      not significantly phosphorylated in response to nitrosative stress, yet it
      displays nuclear accumulation and contributes to the global transcriptional
      response to this stress, as well as promoting nitrosative-stress resistance.
      Instead, nitrosative stress triggers changes in the redox status of Hog1. We also
      show that specific Hog1 cysteine residues influence its activation of stress
      genes. Therefore, alternative posttranslational modifications appear to regulate
      the stress-specific outputs of MAP kinases.

PMID- 29588409
TI  - Physiological Effect of XoxG(4) on Lanthanide-Dependent Methanotrophy.
AB  - A recent surprising discovery of the activity of rare earth metals (lanthanides)
      as enzyme cofactors as well as transcriptional regulators has overturned the
      traditional assumption of biological inertia of these metals. However, so far,
      examples of such activities have been limited to alcohol dehydrogenases. Here we
      describe the physiological effects of a mutation in xoxG, a gene encoding a novel
      cytochrome, XoxG(4), and compare these to the effects of mutation in XoxF, a
      lanthanide-dependent methanol dehydrogenase, at the enzyme activity level and
      also at the community function level, using Methylomonas sp. strain LW13 as a
      model organism. Through comparative phenotypic characterization, we establish
      XoxG as the second protein directly involved in lanthanide-dependent metabolism,
      likely as a dedicated electron acceptor from XoxF. However, mutation in XoxG
      caused a phenotype that was dramatically different from the phenotype of the
      mutant in XoxF, suggesting a secondary function for this cytochrome, in
      metabolism of methane. We also purify XoxG(4) and demonstrate that this protein
      is a true cytochrome c, based on the typical absorption spectra, and we
      demonstrate that XoxG can be directly reduced by a purified XoxF, supporting one
      of its proposed physiological functions. Overall, our data continue to suggest
      the complex nature of the interplay between the calcium-dependent and lanthanide
      dependent alcohol oxidation systems, while they also suggest that addressing the
      roles of these alternative systems is essential at the enzyme and community
      function level, in addition to the gene transcription level.IMPORTANCE The
      lanthanide-dependent biochemistry of living organisms remains a barely tapped
      area of knowledge. So far, only a handful of lanthanide-dependent alcohol
      dehydrogenases have been described, and their regulation by lanthanides has been
      demonstrated at the transcription level. Little information is available
      regarding the concentrations of lanthanides that could support sufficient
      enzymatic activities to support specific metabolisms, and so far, no other redox
      proteins involved in lanthanide-dependent methanotrophy have been demonstrated.
      The research presented here provides enzyme activity-level data on lanthanide
      dependent methanotrophy in a model methanotroph. Additionally, we identify a
      second protein important for lanthanide-dependent metabolism in this organism,
      XoxG(4), a novel cytochrome. XoxG(4) appears to have multiple functions in
      methanotrophy, one function as an electron acceptor from XoxF and another
      function remaining unknown. On the basis of the dramatic phenotype of the XoxG(4)
      mutant, this function must be crucial for methanotrophy.

PMID- 29588410
TI  - Neighbourhood alcohol environment and injury risk: a spatial analysis of
      pedestrian injury in Baltimore City.
AB  - OBJECTIVES: The purpose of this study was to investigate the contribution of
      neighbourhood disorder around alcohol outlets to pedestrian injury risk. METHODS:
      A spatial analysis was conducted on census block groups in Baltimore City. Data
      included pedestrian injury EMS records from 1 January 2014 to 15 April 2015
      (n=858), off-premise alcohol outlet locations for 2014 (n=693) and neighbourhood
      disorder indicators and demographics. Negative binomial regression models were
      used to determine the relationship between alcohol outlet count and pedestrian
      injuries at the block group level, controlling for other neighbourhood factors.
      Attributable risk was calculated by comparing the total population count per
      census block group to the injured pedestrian count. RESULTS: Each one-unit
      increase in the number of alcohol outlets was associated with a 14.2% (95% CI
      1.099 to 1.192, P<0.001) increase in the RR of neighbourhood pedestrian injury,
      adjusting for traffic volume, pedestrian volume, population density, per cent of
      vacant lots and median household income. The attributable risk was 10.4% (95% CI
      7.7 to 12.7) or 88 extra injuries. Vacant lots was the only significant
      neighbourhood disorder indicator in the final adjusted model (RR=1.016, 95% CI
      1.007 to 1.026, P=0.003). Vacant lots have not been previously investigated as
      possible risk factors for pedestrian injury. CONCLUSIONS: This study identifies
      modifiable risk factors for pedestrian injury previously unexplored in the
      literature and may provide evidence for alcohol control strategies (eg, liquor
      store licencing, zoning and enforcement).

PMID- 29588411
TI  - The p85 isoform of the kinase S6K1 functions as a secreted oncoprotein to
      facilitate cell migration and tumor growth.
AB  - Cancer cells can remodel surrounding microenvironments to facilitate cell growth,
      invasion, and migration by secreting proteins that educate surrounding stromal
      cells. We report that p85S6K1, the longest isoform of S6K (ribosomal protein S6
      kinase), but not the shorter isoform p70S6K1 or p56S6K2, was secreted from cancer
      cells through its HIV TAT-like, N-terminal six-arginine motif. The exogenously
      produced p85S6K1 protein entered cultured transformed and nontransformed cells to
      promote or confer malignant behaviors, leading to increased cell growth and
      migration. When injected into mice, the p85S6K1 protein enhanced the growth of
      xenografted breast cancer cells and lung metastasis. Hence, our findings reveal a
      role for p85S6K1 as a secreted oncogenic kinase and provide a mechanism by which
      cancer cells remodel their microenvironment by transforming the surrounding cells
      to drive tumorigenesis.

PMID- 29588412
TI  - Palmitoylation of delta-catenin promotes kinesin-mediated membrane trafficking of
      Nav1.6 in sensory neurons to promote neuropathic pain.
AB  - Palmitoylation of delta-catenin is critical to synapse plasticity and memory
      formation. We found that delta-catenin palmitoylation is also instrumental in the
      development of neuropathic pain. The abundances of palmitoylated delta-catenin
      and the palmitoyl acyltransferase DHHC3 were increased in dorsal root ganglion
      (DRG) sensory neurons in rat models of neuropathic pain. Inhibiting palmitoyl
      acyltransferases or decreasing delta-catenin abundance in the DRG by intrathecal
      injection of 2-bromopalmitate or shRNA, respectively, alleviated oxaliplatin or
      nerve injury-induced neuropathic pain in the rats. The palmitoylation of delta
      catenin, which was induced by the inflammatory cytokine TNF-alpha, facilitated
      its interaction with the voltage-gated sodium channel Nav1.6 and the kinesin
      motor protein KIF3A, which promoted the trafficking of Nav1.6 to the plasma
      membrane in DRG neurons and contributed to mechanical hypersensitivity and
      allodynia in rats. These findings suggest that a palmitoylation-mediated
      KIF3A/delta-catenin/Nav1.6 complex enhances the transmission of mechanical and
      nociceptive signals; thus, blocking this mechanism may be therapeutic in patients
      with neuropathic pain.

PMID- 29588413
TI  - Hydrophobic patches on SMAD2 and SMAD3 determine selective binding to cofactors.
AB  - The transforming growth factor-beta (TGF-beta) superfamily of cytokines regulates
      various biological processes, including cell proliferation, immune responses,
      autophagy, and senescence. Dysregulation of TGF-beta signaling causes various
      diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription
      factors involved in TGF-beta signaling, and they form heterotrimeric complexes
      with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in
      response to TGF-beta signaling. These heterotrimeric complexes interact with
      cofactors to control the expression of TGF-beta-dependent genes. SMAD2 and SMAD3
      may promote or repress target genes depending on whether they form complexes with
      other transcription factors, coactivators, or corepressors; therefore, the
      selection of specific cofactors is critical for the appropriate activity of these
      transcription factors. To reveal the structural basis by which SMAD2 and SMAD3
      select cofactors, we determined the crystal structures of SMAD3 in complex with
      the transcription factor FOXH1 and SMAD2 in complex with the transcriptional
      corepressor SKI. The structures of the complexes show that the MAD homology 2
      (MH2) domains of SMAD2 and SMAD3 have multiple hydrophobic patches on their
      surfaces. The cofactors tether to various subsets of these patches to interact
      with SMAD2 and SMAD3 in a cooperative or competitive manner to control the output
      of TGF-beta signaling.

PMID- 29588414
TI  - Genetic variation in VAC14 is associated with bacteremia secondary to diverse
      pathogens in African children.

PMID- 29588415
TI  - Nonmonotonic spatial structure of interneuronal correlations in prefrontal
      microcircuits.
AB  - Correlated fluctuations of single neuron discharges, on a mesoscopic scale,
      decrease as a function of lateral distance in early sensory cortices, reflecting
      a rapid spatial decay of lateral connection probability and excitation. However,
      spatial periodicities in horizontal connectivity and associational input as well
      as an enhanced probability of lateral excitatory connections in the association
      cortex could theoretically result in nonmonotonic correlation structures. Here,
      we show such a spatially nonmonotonic correlation structure, characterized by
      significantly positive long-range correlations, in the inferior convexity of the
      macaque prefrontal cortex. This functional connectivity kernel was more
      pronounced during wakefulness than anesthesia and could be largely attributed to
      the spatial pattern of correlated variability between functionally similar
      neurons during structured visual stimulation. These results suggest that the
      spatial decay of lateral functional connectivity is not a common organizational
      principle of neocortical microcircuits. A nonmonotonic correlation structure
      could reflect a critical topological feature of prefrontal microcircuits,
      facilitating their role in integrative processes.

PMID- 29588416
TI  - Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium.
AB  - Programmed cell death 5 (PDCD5) has been associated with human cancers as a
      regulator of cell death; however, the role of PDCD5 in the endothelium has not
      been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B
      (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction
      in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5
      knockout mice showed significantly reduced vascular remodeling compared with wild
      type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited
      interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3
      binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT
      interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in
      human umbilical vein endothelial cells. Moreover, we found that serum PDCD5
      levels reflect endothelial NO production and are correlated with diabetes
      mellitus, high-density lipoprotein cholesterol, and coronary calcium in human
      samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude
      that PDCD5 is associated with endothelial dysfunction and may be a novel
      therapeutic target in atherosclerosis.

PMID- 29588417
TI  - Local protein solvation drives direct down-conversion in phycobiliprotein PC645
      via incoherent vibronic transport.
AB  - The mechanisms controlling excitation energy transport (EET) in light-harvesting
      complexes remain controversial. Following the observation of long-lived beats in
      2D electronic spectroscopy of PC645, vibronic coherence, the delocalization of
      excited states between pigments supported by a resonant vibration, has been
      proposed to enable direct excitation transport from the highest-energy to the
      lowest-energy pigments, bypassing a collection of intermediate states. Here, we
      instead show that for phycobiliprotein PC645 an incoherent vibronic transport
      mechanism is at play. We quantify the solvation dynamics of individual pigments
      using ab initio quantum mechanics/molecular mechanics (QM/MM) nuclear dynamics.
      Our atomistic spectral densities reproduce experimental observations ranging from
      absorption and fluorescence spectra to the timescales and selectivity of down
      conversion observed in transient absorption measurements. We construct a general
      model for vibronic dimers and establish the parameter regimes of coherent and
      incoherent vibronic transport. We demonstrate that direct down-conversion in
      PC645 proceeds incoherently, enhanced by large reorganization energies and a
      broad collection of high-frequency vibrations. We suggest that a similar
      incoherent mechanism is appropriate across phycobiliproteins and represents a
      potential design principle for nanoscale control of EET.

PMID- 29588418
TI  - Successful reprogramming of cellular protein production through mRNA delivered by
      functionalized lipid nanoparticles.
AB  - The development of safe and efficacious gene vectors has limited greatly the
      potential for therapeutic treatments based on messenger RNA (mRNA). Lipid
      nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA),
      helper lipids (distearoylphosphatidylcholine, DSPC, and cholesterol), and a
      poly(ethylene glycol) (PEG) lipid have been identified as very promising delivery
      vectors of short interfering RNA (siRNA) in different clinical phases; however,
      delivery of high-molecular weight RNA has been proven much more demanding. Herein
      we elucidate the structure of hEPO modified mRNA-containing LNPs of different
      sizes and show how structural differences affect transfection of human adipocytes
      and hepatocytes, two clinically relevant cell types. Employing small-angle
      scattering, we demonstrate that LNPs have a disordered inverse hexagonal internal
      structure with a characteristic distance around 6 nm in presence of mRNA, whereas
      LNPs containing no mRNA do not display this structure. Furthermore, using
      contrast variation small-angle neutron scattering, we show that one of the lipid
      components, DSPC, is localized mainly at the surface of mRNA-containing LNPs. By
      varying LNP size and surface composition we demonstrate that both size and
      structure have significant influence on intracellular protein production. As an
      example, in both human adipocytes and hepatocytes, protein expression levels for
      130 nm LNPs can differ as much as 50-fold depending on their surface
      characteristics, likely due to a difference in the ability of LNP fusion with the
      early endosome membrane. We consider these discoveries to be fundamental and
      opening up new possibilities for rational design of synthetic nanoscopic vehicles
      for mRNA delivery.

PMID- 29588419
TI  - TWEAK and RIPK1 mediate a second wave of cell death during AKI.
AB  - Acute kidney injury (AKI) is characterized by necrotic tubular cell death and
      inflammation. The TWEAK/Fn14 axis is a mediator of renal injury. Diverse pathways
      of regulated necrosis have recently been reported to contribute to AKI, but there
      are ongoing discussions on the timing or molecular regulators involved. We have
      now explored the cell death pathways induced by TWEAK/Fn14 activation and their
      relevance during AKI. In cultured tubular cells, the inflammatory cytokine TWEAK
      induces apoptosis in a proinflammatory environment. The default inhibitor of
      necroptosis [necrostatin-1 (Nec-1)] was protective, while caspase inhibition
      switched cell death to necroptosis. Additionally, folic acid-induced AKI in mice
      resulted in increased expression of Fn14 and necroptosis mediators, such as
      receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage domain
      like protein (MLKL). Targeting necroptosis with Nec-1 or by genetic RIPK3
      deficiency and genetic Fn14 ablation failed to be protective at early time points
      (48 h). However, a persistently high cell death rate and kidney dysfunction (72
      96 h) were dependent on an intact TWEAK/Fn14 axis driving necroptosis. This was
      prevented by Nec-1, or MLKL, or RIPK3 deficiency and by Nec-1 stable (Nec-1s)
      administered before or after induction of AKI. These data suggest that initial
      kidney damage and cell death are amplified through recruitment of inflammation
      dependent necroptosis, opening a therapeutic window to treat AKI once it is
      established. This may be relevant for clinical AKI, since using current
      diagnostic criteria, severe injury had already led to loss of renal function at
      diagnosis.

PMID- 29588422
TI  - A Conversation with Monica Bettencourt-Dias.

PMID- 29588423
TI  - A Conversation with Marisa Bartolomei.

PMID- 29588420
TI  - Comprehensive, high-resolution binding energy landscapes reveal context
      dependencies of transcription factor binding.
AB  - Transcription factors (TFs) are primary regulators of gene expression in cells,
      where they bind specific genomic target sites to control transcription.
      Quantitative measurements of TF-DNA binding energies can improve the accuracy of
      predictions of TF occupancy and downstream gene expression in vivo and shed light
      on how transcriptional networks are rewired throughout evolution. Here, we
      present a sequencing-based TF binding assay and analysis pipeline (BET-seq, for
      Binding Energy Topography by sequencing) capable of providing quantitative
      estimates of binding energies for more than one million DNA sequences in parallel
      at high energetic resolution. Using this platform, we measured the binding
      energies associated with all possible combinations of 10 nucleotides flanking the
      known consensus DNA target interacting with two model yeast TFs, Pho4 and Cbf1. A
      large fraction of these flanking mutations change overall binding energies by an
      amount equal to or greater than consensus site mutations, suggesting that current
      definitions of TF binding sites may be too restrictive. By systematically
      comparing estimates of binding energies output by deep neural networks (NNs) and
      biophysical models trained on these data, we establish that dinucleotide (DN)
      specificities are sufficient to explain essentially all variance in observed
      binding behavior, with Cbf1 binding exhibiting significantly more nonadditivity
      than Pho4. NN-derived binding energies agree with orthogonal biochemical
      measurements and reveal that dynamically occupied sites in vivo are both
      energetically and mutationally distant from the highest affinity sites.

PMID- 29588421
TI  - Reply to Gilchrist et al.: Possible roles for VAC14 in multiple infectious
      diseases.

PMID- 29588424
TI  - News Feature: What happens when lab animals go wild.

PMID- 29588426
TI  - SULFATION PATHWAYS: Potential benefits of a sulfated resveratrol derivative for
      topical application.
AB  - Resveratrol (RSV) is a polyphenolic compound with antioxidant, anti-inflammatory
      and anti-aging properties partly associated with sirtuin 1 (SIRT1)-activation in
      the skin. However, poor water solubility may limit RSV efficacy. This work aimed
      to clarify the interest of a new synthetic water-soluble RSV derivative
      (resveratrol glucoside sulfate, RSV-GS) for topical application. Resveratrol
      glucoside sulfate was synthesized using microwave-assisted sulfation.
      Cytotoxicity assays were performed with the keratinocyte HaCaT cell line, using
      MTT reduction, neutral red uptake, Alamar Blue/resazurin reduction, trypan blue
      exclusion and measurement of ATP concentration. Western blotting was used to
      evaluate SIRT1 protein content. Regarding SIRT1 binding, an in silico docking
      study was performed, using AutoDock Vina. Our results showed that the synthetic
      derivative RSV-GS was 1000 times more soluble in water than RSV and its non
      sulfated glucoside. No relevant decrease in HaCaT cell viability was observed for
      concentrations up to 5 mM for RSV-GS, and up to 500 MUM for resveratrol
      glucoside, while a significant decrease in HaCaT viability occurred from 100 MUM
      for RSV. RSV-GS and RSV showed a similar behavior regarding protective effect
      against oxidative stress-induced cytotoxicity. SIRT1 protein content increased
      after treatment with 500 MUM of RSV-GS and 100 MUM of RSV. Moreover, in silico
      studies predicted that RSV-GS binds more stably to SIRT1 with a lower binding
      free energy than RSV. Although these results support the possible use of RSV-GS
      in topical formulations, in vivo safety and efficacy studies are needed before
      considering the use of RSV-GS in commercial products.

PMID- 29588428
TI  - SULFATION PATHWAYS: Expression of SULT2A1, SULT2B1 and HSD3B1 in the porcine
      testis and epididymis.
AB  - In the porcine testis, in addition to estrogen sulfates, the formation of
      numerous sulfonated neutral hydroxysteroids has been observed. However, their
      functions and the underlying synthetic pathways are still widely unclear. To
      obtain further information on their formation in postpubertal boars, the
      expression of sulfotransferases considered relevant for neutral hydroxysteroids
      (SULT2A1, SULT2B1) was investigated in the testis and defined segments of the
      epididymis applying real-time RT-qPCR, Western blot and immunohistochemistry
      (IHC). Sulfotransferase activities were assessed in tissue homogenates or
      cytosolic preparations applying dehydroepiandrosterone and pregnenolone as
      substrates. A high SULT2A1 expression was confirmed in the testis and localized
      in Leydig cells by IHC. In the epididymis, SULT2A1 expression was virtually
      confined to the body. SULT2B1 expression was absent or low in the testis but
      increased significantly along the epididymis. Immunohistochemical observations
      indicate that both enzymes are secreted into the ductal lumen via an apocrine
      mechanism. The results from the characterization of expression patterns and
      activity measurements suggest that SULT2A1 is the prevailing enzyme for the
      sulfonation of hydroxysteroids in the testis, whereas SULT2B1 may catalyze the
      formation of sterol sulfates in the epididymis. In order to obtain information on
      the overall steroidogenic capacity of the porcine epididymis, the expression of
      important steroidogenic enzymes (CYP11A1, CYP17A1, CYP19, HSD3B1, HSD17B3,
      SRD5A2) was monitored in the defined epididymal segments applying real-time RT
      qPCR. Surprisingly, in addition to a high expression of SRD5A2 in the epididymal
      head, a substantial expression of HSD3B1 was detected, which increased along the
      organ.

PMID- 29588427
TI  - Molecular mechanisms of glucocorticoids on skeleton and bone regeneration after
      fracture.
AB  - Glucocorticoid hormones (GCs) have profound effects on bone metabolism. Via their
      nuclear hormone receptor - the GR - they act locally within bone cells and
      modulate their proliferation, differentiation, and cell death. Consequently, high
      glucocorticoid levels - as present during steroid therapy or stress - impair bone
      growth and integrity, leading to retarded growth and glucocorticoid-induced
      osteoporosis, respectively. Because of their profound impact on the immune system
      and bone cell differentiation, GCs also affect bone regeneration and fracture
      healing. The use of conditional-mutant mouse strains in recent research provided
      insights into the cell-type-specific actions of the GR. However, despite recent
      advances in system biology approaches addressing GR genomics in general, little
      is still known about the molecular mechanisms of GCs and GR in bone cells. Here,
      we review the most recent findings on the molecular mechanisms of the GR in
      general and the known cell-type-specific actions of the GR in mesenchymal cells
      and their derivatives as well as in osteoclasts during bone homeostasis, GC
      excess, bone regeneration and fracture healing.

PMID- 29588429
TI  - Hydroxyproline Metabolism and Oxalate Synthesis in Primary Hyperoxaluria.
AB  - Background Endogenous oxalate synthesis contributes to calcium oxalate stone
      disease and is markedly increased in the inherited primary hyperoxaluria (PH)
      disorders. The incomplete knowledge regarding oxalate synthesis complicates
      discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the
      formation of oxalate and glycolate. However, the relative contribution of Hyp
      metabolism to endogenous oxalate and glycolate synthesis is not known.Methods To
      define this contribution, we performed primed, continuous, intravenous infusions
      of the stable isotope [15N,13C5]-Hyp in nine healthy subjects and 19 individuals
      with PH and quantified the levels of urinary 13C2-oxalate and 13C2-glycolate
      formed using ion chromatography coupled to mass detection.Results The total
      urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and
      10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls,
      respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g
      creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg
      oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was
      15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3,
      respectively. The contribution of Hyp to urinary glycolate was 57% in controls,
      30% in subjects with PH1, and <13% in subjects with PH2 or PH3.Conclusions Hyp
      metabolism differs among PH types and is a major source of oxalate synthesis in
      individuals with PH2 and PH3. In patients with PH1, who have the highest urinary
      excretion of oxalate, the major sources of oxalate remain to be identified.

PMID- 29588433
TI  - Sexual Dysfunction in Patients with Antidepressant-treated Anxiety or Depressive
      Disorders: a Pragmatic Multivariable Longitudinal Study.
AB  - OBJECTIVE: To investigate early evolution, tolerability, and predictors of
      antidepressant-emergent sexual dysfunction in patients with anxiety or depressive
      disorder. METHODS: Patients with anxiety or depressive disorders who were
      prescribed antidepressant monotherapy (mirtazapine, sertraline, desvenlafaxine,
      escitalopram, or fluoxetine) at the discretion of the treating clinician were
      recruited from July 2012 to June 2014 from a hospital outpatient service. All
      were free of psychotropic medication for least 1 month. Sexual function was
      assessed at baseline, week 2, and week 6 using the Psychotropic-Related Sexual
      Dysfunction Questionnaire (PRSexDQ). A PRSexDQ score of >=2 was considered to
      indicate sexual dysfunction. Sexual function was dichotomised to 'favourable' or
      'impaired'. RESULTS: Of 230 patients recruited, 209 were assessed at baseline of
      whom 184 were assessed at week 2; of these, 154 were also assessed at week 6. At
      baseline, 138 (66%) of the 209 patients were diagnosed with depressive disorder
      and 71 (34%) with anxiety disorder; 29% of patients had sexual dysfunction (in
      any domain of PRSexDQ). By week 6, the percentage had increased to 41%, although
      the change in the mean PRSexDQ score was only marginal (from 1.04 at baseline to
      1.55 at week 6). With regard to individual questionnaire items, by week 6, sexual
      desire improved, but erectile and ejaculatory function in men and orgasmic
      function in women worsened. Fluoxetine and sertraline were associated with
      impaired sexual function, whereas mirtazapine was associated with favourable
      sexual function. In a logistic regression analysis, at week 2, mirtazapine and
      desvenlafaxine were predictors of favourable sexual outcome, whereas fluoxetine
      and higher baseline PRSexDQ score were predictors of impaired sexual outcome. At
      week 6, mirtazapine remained a predictor of favourable sexual outcome, whereas
      fluoxetine, higher 2-week PRSexDQ score, and adequate dose were predictors of
      impaired sexual outcome. CONCLUSIONS: In patients with anxiety or depressive
      disorder, the risk of antidepressant-emergent sexual dysfunction at 6 weeks is
      low when drug doses are initially low with gradual up-titration. Baseline sexual
      dysfunction was independently associated with impaired sexual outcome. Men may be
      more likely than women to experience impaired sexual outcome. In patients with
      baseline sexual dysfunction, prescription of mirtazapine might be preferable to
      fluoxetine.

PMID- 29588430
TI  - An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy.
AB  - Background C3 glomerulopathy (C3G) is associated with dysregulation of the
      alternative pathway of complement activation, and treatment options for C3G
      remain limited. Complement factor H (FH) is a potent regulator of the alternative
      pathway and might offer a solution, but the mass and complexity of FH makes
      generation of full-length FH far from trivial. We previously generated a mini-FH
      construct, with FH short consensus repeats 1-5 linked to repeats 18-20 (FH1-5^18
      20), that was effective in experimental C3G. However, the serum t1/2 of FH1-5^18
      20 was significantly shorter than that of serum-purified FH.Methods We introduced
      the oligomerization domain of human FH-related protein 1 (denoted by R1-2) at the
      carboxy or amino terminus of human FH1-5^18-20 to generate two homodimeric mini
      FH constructs (FHR1-2^1-5^18-20 and FH1-5^18-20^R1-2, respectively) in Chinese
      hamster ovary cells and tested these constructs using binding, fluid-phase, and
      erythrocyte lysis assays, followed by experiments in FH-deficient Cfh-/-
      mice.Results FHR1-2^1-5^18-20 and FH1-5^18-20^R1-2 homodimerized in solution and
      displayed avid binding profiles on clustered C3b surfaces, particularly FHR1-2^1
      5^18-20 Each construct was >10-fold more effective than FH at inhibiting cell
      surface complement activity in vitro and restricted glomerular basement membrane
      C3 deposition in vivo significantly better than FH or FH1-5^18-20 FH1-5^18-20^R1
      2 had a C3 breakdown fragment binding profile similar to that of FH, a >5-fold
      increase in serum t1/2 compared with that of FH1-5^18-20, and significantly
      better retention in the kidney than FH or FH1-5^18-20Conclusions FH1-5^18-20^R1-2
      may have utility as a treatment option for C3G or other complement-mediated
      diseases.

PMID- 29588434
TI  - Implementing of a problem-based learning strategy in a Saudi medical school:
      requisites and challenges.

PMID- 29588435
TI  - Factors Associated with Health-Related Quality of Life in Korean Patients with
      Chronic Hepatitis C Infection Using the SF-36 and EQ-5D.
AB  - Background/Aims: This study aimed to describe the health-related quality of life
      (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the
      impact of patient and virus-related factors on HRQoL. Methods: HRQoL was assessed
      in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary
      hospital, including those with liver cirrhosis and hepatocellular carcinoma
      (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life
      questionnaire-5 dimensions (EQ-5D-3L). Results: The SF-36 physical (48.8+/-8.3)
      and mental (46.2+/-11.7) component summary scores of the HCV-infected patients
      were below normal limits. Of the eight domains, general health, vitality, and
      mental health tended to show low scores. Patients with decompensated cirrhosis
      had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL
      results. The EQ-5D index was low (0.848+/-0.145) in the HCV infected patients.
      Multivariable analysis showed age <=65 years, high monthly family income
      (>$2,641), low comorbidity score, and sustained virologic response (SVR) were
      independently associated with favorable HRQoL. Conclusions: HRQoL in Korean
      patients with chronic HCV infection was low and was affected by cirrhosis
      severity, SVR, and comorbidity as well as income, which had the strongest effect.
      Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to
      prevent cirrhosis progression.

PMID- 29588437
TI  - Time-gated scintillator imaging for real-time optical surface dosimetry in total
      skin electron therapy.
AB  - The purpose of this study was to measure surface dose by remote time-gated
      imaging of plastic scintillators. A novel technique for time-gated, intensified
      camera imaging of scintillator emission was demonstrated, and key parameters
      influencing the signal were analyzed, including distance, angle and thickness. A
      set of scintillator samples was calibrated by using thermo-luminescence detector
      response as reference. Examples of use in total skin electron therapy are
      described. The data showed excellent room light rejection (signal-to-noise ratio
      of scintillation SNR  ~  470), ideal scintillation dose response linearity, and
      2% dose rate error. Individual sample scintillation response varied by 7% due to
      sample preparation. Inverse square distance dependence correction and lens
      throughput error (8% per meter) correction were needed. At scintillator-to-source
      angle and observation angle  <50 degrees , the radiant energy fluence error was
      smaller than 1%. The achieved standard error of the scintillator cumulative dose
      measurement compared to the TLD dose was 5%. The results from this proof-of
      concept study documented the first use of small scintillator targets for remote
      surface dosimetry in ambient room lighting. The measured dose accuracy renders
      our method to be comparable to thermo-luminescent detector dosimetry, with the
      ultimate realization of accuracy likely to be better than shown here. Once
      optimized, this approach to remote dosimetry may substantially reduce the time
      and effort required for surface dosimetry.

PMID- 29588436
TI  - Long-Term Clinical Outcomes of Endoscopic Submucosal Dissection in Patients with
      Early Gastric Cancer: A Prospective Multicenter Cohort Study.
AB  - Background/Aims: Endoscopic submucosal dissection (ESD) has been regarded as a
      curative treatment for early gastric cancer (EGC) in indicated cases. The aim of
      this study was to evaluate the nationwide long-term clinical outcomes of ESD for
      EGC in Korea. Methods: A prospective multicenter cohort study was performed to
      evaluate the long-term efficacy of ESD for EGC within pre-defined indications at
      12 institutes in Korea. The cases that met the expanded criteria upon
      pathological review after ESD were followed for 5 years. The primary outcome was
      5-year disease specific free survival. Results: Six hundred ninety-seven patients
      with 722 EGCs treated with ESD were prospectively enrolled and followed for 5
      years. Complete resection was achieved in 81.3% of the cases, and curative
      resection was achieved in 86.1%. During the 5-year follow-up, the overall
      survival rate was 96.6%, and the disease specific free survival rate was 90.6%.
      Local recurrence developed in 0.9%, and metachronous tumor development occurred
      in 7.8%; both conditions were treated by endoscopic or surgical treatment.
      Distant metastasis developed in 0.5% during follow-up. Conclusions: ESD showed
      excellent long-term clinical outcomes and can be accepted as a curative treatment
      for patients with EGC who meet the expanded criteria in final pathology studies.

PMID- 29588438
TI  - Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1
      (MALAT1) Promotes Renal Cell Carcinoma Progression via Sponging miRNA-429.

PMID- 29588439
TI  - Torsion of the Vermiform Appendix: A Case Report and Review of Literature.

PMID- 29588440
TI  - Retracted: Effect of Over-Expression of Zinc-Finger Protein (ZFX) on Self-Renewal
      and Drug-Resistance of Hepatocellular Carcinoma.

PMID- 29588442
TI  - Addendum: Access to stereodefined (Z)-allylsilanes and (Z)-allylic alcohols via
      cobalt-catalyzed regioselective hydrosilylation of allenes.

PMID- 29588441
TI  - Hunting regulation favors slow life histories in a large carnivore.
AB  - As an important extrinsic source of mortality, harvest should select for fast
      reproduction and accelerated life histories. However, if vulnerability to harvest
      depends upon female reproductive status, patterns of selectivity could diverge
      and favor alternative reproductive behaviors. Here, using more than 20 years of
      detailed data on survival and reproduction in a hunted large carnivore
      population, we show that protecting females with dependent young, a widespread
      hunting regulation, provides a survival benefit to females providing longer
      maternal care. This survival gain compensates for the females' reduced
      reproductive output, especially at high hunting pressure, where the fitness
      benefit of prolonged periods of maternal care outweighs that of shorter maternal
      care. Our study shows that hunting regulation can indirectly promote slower life
      histories by modulating the fitness benefit of maternal care tactics. We provide
      empirical evidence that harvest regulation can induce artificial selection on
      female life history traits and affect demographic processes.

PMID- 29588443
TI  - GS9 acts as a transcriptional activator to regulate rice grain shape and
      appearance quality.
AB  - Identification of grain shape determining genes can facilitate breeding of rice
      cultivars with optimal grain shape and appearance quality. Here, we identify GS9
      (Grain Shape Gene on Chromosome 9) gene by map-based cloning. The gs9 null mutant
      has slender grains, while overexpression GS9 results in round grains. GS9 encodes
      a protein without known conserved functional domain. It regulates grain shape by
      altering cell division. The interaction of GS9 and ovate family proteins OsOFP14
      and OsOFP8 is modulated by OsGSK2 kinase, a key regulator of the brassinosteroids
      signaling pathway. Genetic interaction analysis reveals that GS9 functions
      independently from other previously identified grain size genes. Introducing the
      gs9 allele into elite rice cultivars significantly improves grain shape and
      appearance quality. It suggests potential application of gs9, alone or in
      combination with other grain size determining genes, in breeding of rice
      varieties with optimized grain shape.

PMID- 29588444
TI  - Pre-Columbian earth-builders settled along the entire southern rim of the Amazon.
AB  - The discovery of large geometrical earthworks in interfluvial settings of
      southern Amazonia has challenged the idea that Pre-Columbian populations were
      concentrated along the major floodplains. However, a spatial gap in the
      archaeological record of the Amazon has limited the assessment of the territorial
      extent of earth-builders. Here, we report the discovery of Pre-Columbian ditched
      enclosures in the Tapajos headwaters. The results show that an 1800 km stretch of
      southern Amazonia was occupied by earth-building cultures living in fortified
      villages ~Cal AD 1250-1500. We model earthwork distribution in this broad region
      using recorded sites, with environmental and terrain variables as predictors,
      estimating that earthworks will be found over ~400,000 km2 of southern Amazonia.
      We conclude that the interfluves and minor tributaries of southern Amazonia
      sustained high population densities, calling for a re-evaluation of the role of
      this region for Pre-Columbian cultural developments and environmental impact.

PMID- 29588445
TI  - Solvent Composition Drives the Rebinding Kinetics of Nitric Oxide to
      Microperoxidase.
AB  - The rebinding kinetics of NO after photodissociation from microperoxidase (Mp-9)
      is studied in different solvent environments. In mixed glycerol/water (G/W)
      mixtures the dissociating ligand rebinds with a yield close to 1 due to the
      cavities formed by the solvent whereas in pure water the ligand can diffuse into
      the solvent after photodissociation. In the G/W mixture, only geminate rebinding
      on the sub-picosecond and 5 ps time scales was found and the rebinding fraction
      is unity which compares well with available experiments. Contrary to that,
      simulations in pure water find two time scales - ~10 ps and ~200 ps - indicating
      that both, geminate rebinding and rebinding after diffusion of NO in the
      surrounding water contribute. The rebinding fraction is around 0.63 within 1 ns
      which is in stark contrast with experiment. Including ions (Na and Cl) at 0.15 M
      concentration in water leads to rebinding kinetics tending to that in the
      glycerol/water mixture and yields agreement with experiments. The effect of
      temperature is also probed and found to be non-negligible. The present
      simulations suggest that NO rebinding in Mp is primarily driven by thermal
      fluctuations which is consistent with recent resonance Raman spectroscopy
      experiments and simulations on MbNO.

PMID- 29588446
TI  - Enhancing doping contrast and optimising quantification in the scanning electron
      microscope by surface treatment and Fermi level pinning.
AB  - Recent advances in two-dimensional dopant profiling in the scanning electron
      microscope have enabled a high throughput, non-contact process diagnostics and
      failure analysis solution for integrated device manufacturing. The routine
      (electro)chemical etch processes to obtain contamination-free, hydrogen
      terminated silicon surfaces is industrially important in ULSI microfabrication,
      though doping contrast, which is the basis for quantitative dopant profiling,
      will be strongly altered. We show herein that ammonium-fluoride treatment not
      only enabled doping contrast to be differentiated mainly by surface band-bending,
      but it enhanced the quality of linear quantitative calibration through simple
      univariate analysis for SE energies as low as 1 eV. Energy-filtering measurements
      reveal that the linear analytical model broached in the literature (c.f. Kazemian
      et al., 2006 and Kazemian et al., 2007) is likely to be inadequate to determine
      the surface potential across semiconductor p-n junctions without suitable
      deconvolution methods. Nevertheless, quantification trends suggest that energy
      filtering may not be crucial if patch fields and contamination are absolutely
      suppressed by the appropriate edge termination and passivation.

PMID- 29588447
TI  - Enhancing the recovery of a temporal sequence of images using joint
      deconvolution.
AB  - In this work, we address the reconstruction of spatial patterns that are encoded
      in light fields associated with a series of light pulses emitted by a laser
      source and imaged using photon-counting cameras, with an intrinsic response
      significantly longer than the pulse delay. Adopting a Bayesian approach, we
      propose and demonstrate experimentally a novel joint temporal deconvolution
      algorithm taking advantage of the fact that single pulses are observed
      simultaneously by different pixels. Using an intensified CCD camera with a 1000
      ps gate, stepped with 10-ps increments, we show the ability to resolve images
      that are separated by a 10-ps delay, four time better compared to standard
      deconvolution techniques.

PMID- 29588448
TI  - Increasing biomass demand enlarges negative forest nutrient budget areas in wood
      export regions.
AB  - Energy production from biomass is one of the adopted strategies in different
      European countries to limit global warming to within the 1.5-2 degrees  targets
      after the 2015 UN climate agreement. This will motivate enhanced forest harvest
      rates and whole tree harvest to supply the increasing biomass demand. Negative
      nutrient budgets for certain timberland areas where geogenic nutrient supply
      cannot cope with harvesting rates will be one consequence. A spatially explicit
      analysis for a U.S. timberland area of 33,570 km2 reveals that for a minimum
      nutrient loss and supply scenario, negative nutrient budgets occur in 17, 20, 16,
      and almost 94% of the studied areas for Ca, K, Mg, and P, respectively. For a
      maximum nutrient loss (considering intensive harvesting) and supply assumptions,
      the affected areas increase to 50, 57, 45 and 96% for Ca, K, Mg, and P,
      respectively. In general, atmospheric nutrient deposition is of minor importance
      for the high weathering supply cases. Increasing global woody biomass demand may
      cause additional pressure on forested ecosystems, enlarging negative nutrient
      budget areas. If woody biomass demand rises, strategies to counterbalance
      nutrient gaps might be needed, for example, by preparing harvested areas with
      rock products, designed to replenish growth limiting nutrients, and/or
      implementing forest management strategies to minimize nutrient export.

PMID- 29588450
TI  - Reducing electric-field-enhancement in metal-dielectric grating by designing
      grating with asymmetric ridge.
AB  - Diffraction gratings are an essential optical component of high-power, short
      pulse lasers. The maximum output of high-power pulsed lasers is always determined
      by laser resistance of gratings and this resistance is strongly dependent on the
      local near electric field intensity in the grating structure. We presented a
      novel method of reducing electric-field-enhancement in metal-dielectric grating
      by designing asymmetric grating ridge while maintaining high diffraction
      performance. Compared with the common isosceles trapezoidal grating, the grating
      with asymmetric ridge got a 0.04% reduction of diffraction efficiency in TE
      polarization at 1053 nm incident wavelength but a 21.3% reduction of maximal
      electric-field-enhancement in grating structure. This method can be applied to
      any surface-relief gratings to reduce the electric-field-enhancement for
      improving the laser induced damage threshold (LIDT) of grating and supporting the
      grating-based chirped pulse amplification (CPA) system to develop into higher
      peak-power levels.

PMID- 29588449
TI  - Confirmation of a metastasis-specific microRNA signature in primary colon cancer.
AB  - The identification of patients with high-risk stage II colon cancer who may
      benefit from adjuvant therapy may allow the clinical approach to be tailored for
      these patients based on an understanding of tumour biology. MicroRNAs have been
      proposed as markers of the prognosis or treatment response in colorectal cancer.
      Recently, a 2-microRNA signature (let-7i and miR-10b) was proposed to identify
      colorectal cancer patients at risk of developing distant metastasis. We assessed
      the prognostic value of this signature and additional candidate microRNAs in an
      independent, clinically well-defined, prospectively collected cohort of primary
      colon cancer patients including stage I-II colon cancer without and stage III
      colon cancer with adjuvant treatment. The 2-microRNA signature specifically
      predicted hepatic recurrence in the stage I-II group, but not the overall ability
      to develop distant metastasis. The addition of miR-30b to the 2-microRNA
      signature allowed the prediction of both distant metastasis and hepatic
      recurrence in patients with stage I-II colon cancer who did not receive adjuvant
      chemotherapy. Available gene expression data allowed us to associate miR-30b
      expression with axon guidance and let-7i expression with cell adhesion,
      migration, and motility.

PMID- 29588451
TI  - Identification of the functional pathways altered by placental cell exposure to
      high glucose: lessons from the transcript and metabolite interactome.
AB  - The specific consequences of hyperglycaemia on placental metabolism and function
      are incompletely understood but likely contribute to poor pregnancy outcomes
      associated with diabetes mellitus (DM). This study aimed to identify the
      functional biochemical pathways perturbed by placental exposure to high glucose
      levels through integrative analysis of the trophoblast transcriptome and
      metabolome. The human trophoblast cell line, BeWo, was cultured in 5 or 25 mM
      glucose, as a model of the placenta in DM. Transcriptomic analysis using
      microarrays, demonstrated 5632 differentially expressed gene transcripts (>=+/-
      1.3 fold change (FC)) following exposure to high glucose. These genes were used
      to generate interactome models of transcript response using BioGRID (non-inferred
      network: 2500 nodes (genes) and 10541 protein-protein interactions). Ultra
      performance-liquid chromatography-mass spectrometry (MS) and gas chromatography
      MS analysis of intracellular extracts and culture medium were used to assess the
      response of metabolite profiles to high glucose concentration. The interactions
      of altered genes and metabolites were assessed using the MetScape interactome
      database, resulting in an integrated model of systemic transcriptome (2969 genes)
      and metabolome (41 metabolites) response within placental cells exposed to high
      glucose. The functional pathways which demonstrated significant change in
      response to high glucose included fatty acid beta-oxidation, phospholipid
      metabolism and phosphatidylinositol phosphate signalling.

PMID- 29588452
TI  - Monitoring the Age of Mosquito Populations Using Near-Infrared Spectroscopy.
AB  - Mosquito control with bednets, residual sprays or fumigation remains the most
      effective tool for preventing vector-borne diseases such as malaria, dengue and
      Zika, though there are no widely used entomological methods for directly
      assessing its efficacy. Mosquito age is the most informative metric for
      evaluating interventions that kill adult mosquitoes but there is no simple or
      reliable way of measuring it in the field. Near-Infrared Spectroscopy (NIRS) has
      been shown to be a promising, high-throughput method that can estimate the age of
      mosquitoes. Currently the ability of NIRS to measure mosquito age is biased, and
      has relatively high individual mosquito measurement error, though its capacity to
      rigorously monitor mosquito populations in the field has never been assessed. In
      this study, we use machine learning methods from the chemometric literature to
      generate more accurate, unbiased estimates of individual mosquito age. These
      unbiased estimates produce precise population-level measurements, which are
      relatively insensitive to further increases in NIRS accuracy when feasible
      numbers of mosquitoes are sampled. The utility of NIRS to directly measure the
      impact of pyrethroid resistance on mosquito control is illustrated, showing how
      the technology has potential as a highly valuable tool for directly assessing the
      efficacy of mosquito control interventions.

PMID- 29588453
TI  - Erythrocyte's aging in microgravity highlights how environmental stimuli shape
      metabolism and morphology.
AB  - The determination of the function of cells in zero-gravity conditions is a
      subject of interest in many different research fields. Due to their metabolic
      unicity, the characterization of the behaviour of erythrocytes maintained in
      prolonged microgravity conditions is of particular importance. Here, we used a 3D
      clinostat to assess the microgravity-induced modifications of the structure and
      function of these cells, by investigating how they translate these peculiar
      mechanical stimuli into modifications, with potential clinical interest, of the
      biochemical pathways and the aging processes. We compared the erythrocyte's
      structural parameters and selected metabolic indicators that are characteristic
      of the aging in microgravity and standard static incubation conditions. The
      results suggest that, at first, human erythrocytes react to external stimuli by
      adapting their metabolic patterns and the rate of consumption of the cell
      resources. On longer timeframes, the cells translate even small differences in
      the environment mechanical solicitations into structural and morphologic
      features, leading to distinctive morphological patterns of aging.

PMID- 29588454
TI  - The effect of nitrogen lone-pair interaction on the conduction in a single
      molecule junction with amine-Au bonding.
AB  - We have applied our previously developed three-dimensional dynamic probe method
      to analyze the conductance in a Au-/1,4-benzenediamine (BDA)/Au single molecule
      junction. This structure is a typically used example to demonstrate the high
      performance of the break junction (BJ) method for measuring conductance with
      small variations, however, details of the interaction of the nitrogen (N) lone
      pair in the amine group with a Au electrode, which is considered to have a
      fundamental role in determining the conductance of the single molecule junction
      with the amine, have not yet been clarified and still remain an important issue
      to be resolved. In this study, we have succeeded, for the first time, in
      observing the site-dependent change in conductance of this system while the
      molecular conformation was accurately controlled, and the results were well
      reproduced by a simulation taking account of the effect of the N lone-pair in an
      amine bonding with a Au electrode.

PMID- 29588455
TI  - Proteomic and bioinformatic pipeline to screen the ligands of S. pneumoniae
      interacting with human brain microvascular endothelial cells.
AB  - The mechanisms by which Streptococcus pneumoniae penetrates the blood-brain
      barrier (BBB), reach the CNS and causes meningitis are not fully understood.
      Adhesion of bacterial cells on the brain microvascular endothelial cells (BMECs),
      mediated through protein-protein interactions, is one of the crucial steps in
      translocation of bacteria across BBB. In this work, we proposed a systematic
      workflow for identification of cell wall associated ligands of pneumococcus that
      might adhere to the human BMECs. The proteome of S. pneumoniae was biotinylated
      and incubated with BMECs. Interacting proteins were recovered by affinity
      purification and identified by data independent acquisition (DIA). A total of 44
      proteins were identified from which 22 were found to be surface-exposed. Based on
      the subcellular location, ontology, protein interactive analysis and literature
      review, five ligands (adhesion lipoprotein, endo-beta-N-acetylglucosaminidase,
      PhtA and two hypothetical proteins, Spr0777 and Spr1730) were selected to
      validate experimentally (ELISA and immunocytochemistry) the ligand-BMECs
      interaction. In this study, we proposed a high-throughput approach to generate a
      dataset of plausible bacterial ligands followed by systematic bioinformatics
      pipeline to categorize the protein candidates for experimental validation. The
      approach proposed here could contribute in the fast and reliable screening of
      ligands that interact with host cells.

PMID- 29588456
TI  - Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER
      Trafficking.
AB  - Anesthetic agents have been implicated in the causation of neurological and
      cognitive deficits after surgery, the exacerbation of chronic neurodegenerative
      disease, and were recently reported to promote the onset of the neurologic
      respiratory disease Congenital Central Hypoventilation Syndrome (CCHS), related
      to misfolding of the transcription factor Phox2B. To study how anesthetic agents
      could affect neuronal function through alterations to protein folding, we created
      neuronal cell models emulating the graded disease severity of CCHS. We found that
      the gas anesthetic isoflurane and the opiate morphine potentiated aggregation and
      mislocalization of Phox2B variants, similar to that seen in CCHS, and observed
      transcript and protein level changes consistent with activation of the
      endoplasmic reticulum (ER) unfolded protein response. Attenuation of ER stress
      pathways did not result in a correction of Phox2B misfolding, indicating a
      primary effect of isoflurane on protein structure. We also observed that
      isoflurane hindered the folding and activity of proteins that rely heavily on ER
      function, like the CFTR channel. Our results show how anesthetic drugs can alter
      protein folding and induce ER stress, indicating a mechanism by which these
      agents may affect neuronal function after surgery.

PMID- 29588457
TI  - Efficacy and safety of boosted darunavir-based antiretroviral therapy in HIV-1
      positive patients: results from a meta-analysis of clinical trials.
AB  - Darunavir/ritonavir (DRV/r) is a second-generation protease inhibitor used in
      treatment-naive and -experienced HIV-positive adult patients. To evaluate
      efficacy and safety in these patient settings, we performed a meta-analysis of
      randomized controlled trials. We considered eight studies involving 4240
      antiretroviral treatment (ART)-naive patients and 14 studies involving 2684 ART
      experienced patients. Regarding efficacy in the ART-naive patients, the
      virological response rate was not significantly different between DRV/r and the
      comparator. For the ART-experienced failing patients, the virological response
      rate was significantly higher with DRV/r than with the comparator (RR 1.45, 95%
      CI: 1.01-2.08); conversely, no significant differences were found between the
      treatment-experienced and virologically controlled DRV/r and comparator groups.
      Regarding safety, the discontinuation rates due to adverse events (AEs) and DRV/r
      related serious adverse events (SAEs) did not significantly differ from the rates
      in the comparator group (RR 0.84, 95% CI: 0.59-1.19 and RR 0.78, 95% CI: 0.57
      1.05, respectively). Our meta-analysis indicated that DRV/r-based regimens were
      effective and tolerable for both types of patients, which was consistent with
      published data.

PMID- 29588458
TI  - Personalised drug repositioning for Clear Cell Renal Cell Carcinoma using gene
      expression.
AB  - Reversal of cancer gene expression is predictive of therapeutic potential and can
      be used to find new indications for existing drugs (drug repositioning). Gene
      expression reversal potential is currently calculated, in almost all studies, by
      pre-aggregating all tumour samples into a single group signature or a limited
      number of molecular subtype signatures. Here, we investigate whether drug
      repositioning based on individual tumour sample gene expression signatures
      outperforms the use of tumour group and subtype signatures. The tumour signatures
      were created using 534 tumour samples and 72 matched normal samples from 530
      clear cell renal cell carcinoma (ccRCC) patients. More than 20,000 drug
      signatures were extracted from the CMAP and LINCS databases. We show that
      negative enrichment of individual tumour samples correlated (Spearman's rho =
      0.15) much better with the amount of differentially expressed genes in drug
      signatures than with the tumour group signature (Rho = 0.08) and the 4 tumour
      subtype signatures (Rho 0.036-0.11). Targeted drugs used against ccRCC, such as
      sirolimus and temsirolimus, which could not be identified with the pre-aggregated
      tumour signatures could be recovered using individual sample analysis. Thus, drug
      repositioning can be personalized by taking into account the gene expression
      profile of the individual's tumour sample.

PMID- 29588459
TI  - A unified framework for modelling sediment fate from source to sink and its
      interactions with reef systems over geological times.
AB  - Understanding the effects of climatic variability on sediment dynamics is
      hindered by limited ability of current models to simulate long-term evolution of
      sediment transfer from source to sink and associated morphological changes. We
      present a new approach based on a reduced-complexity model which computes over
      geological time: sediment transport from landmasses to coasts, reworking of
      marine sediments by longshore currents, and development of coral reef systems.
      Our framework links together the main sedimentary processes driving mixed
      siliciclastic-carbonate system dynamics. It offers a methodology for objective
      and quantitative sediment fate estimations over regional and millennial time
      scales. A simulation of the Holocene evolution of the Great Barrier Reef shows:
      (1) how high sediment loads from catchments erosion prevented coral growth during
      the early transgression phase and favoured sediment gravity-flows in the deepest
      parts of the northern region basin floor (prior to 8 ka before present (BP)); (2)
      how the fine balance between climate, sea-level, and margin physiography enabled
      coral reefs to thrive under limited shelf sedimentation rates after ~6 ka BP;
      and, (3) how since 3 ka BP, with the decrease of accommodation space, reduced of
      vertical growth led to the lateral extension of reefs consistent with available
      observational data.

PMID- 29588460
TI  - Investigation of the Oxidation Behaviour of Ti and Al in Inconel 718 Superalloy
      During Electroslag Remelting.
AB  - In the current study, the thermodynamics of the slag-metal equilibrium reaction
      between Inconel 718 Ni-based alloy and CaF2-CaO-Al2O3-MgO-TiO2 electroslag
      remelting (ESR)-type slags were systematically investigated in the temperature
      range from 1773 to 1973 K (1500 to 1700  degrees C). The equilibrium Al content
      increased with increasing temperature, whereas the equilibrium Ti content
      decreased with increasing temperature at a fixed slag composition. The important
      factors for controlling the oxidation of Al and Ti in the Inconel 718 superalloy
      were TiO2 > Al2O3 > CaO > CaF2 > MgO in ESR-type slag and Al > Ti in a consumable
      electrode. The conventional method of sampling by means of a quartz tube could
      result in contamination of the molten metal and changes in the size of the
      "special reaction interface". Therefore, a novel method was used in the present
      study to investigate the slag-metal reaction kinetics to accurately obtain the
      kinetic parameters. The mass transfer coefficient was determined by coupling with
      the kinetic model derived from the assumption that the reaction rate ([Al] +
      (TiO2) = [Ti] + (Al2O3)) was controlled by the mass transfer of [Ti], [Al],
      (TiO2) and (Al2O3) in the boundary layer, respectively.

PMID- 29588462
TI  - Spin density wave instability in a ferromagnet.
AB  - Due to its cooperative nature, magnetic ordering involves a complex interplay
      between spin, charge, and lattice degrees of freedom, which can lead to strong
      competition between magnetic states. Binary Fe3Ga4 is one such material that
      exhibits competing orders having a ferromagnetic (FM) ground state, an
      antiferromagnetic (AFM) behavior at intermediate temperatures, and a conspicuous
      re-entrance of the FM state at high temperature. Through a combination of neutron
      diffraction experiments and simulations, we have discovered that the AFM state is
      an incommensurate spin-density wave (ISDW) ordering generated by nesting in the
      spin polarized Fermi surface. These two magnetic states, FM and ISDW, are seldom
      observed in the same material without application of a polarizing magnetic field.
      To date, this unusual mechanism has never been observed and its elemental origins
      could have far reaching implications in many other magnetic systems that contain
      strong competition between these types of magnetic order. Furthermore, the
      competition between magnetic states results in a susceptibility to external
      perturbations allowing the magnetic transitions in Fe3Ga4 to be controlled via
      temperature, magnetic field, disorder, and pressure. Thus, Fe3Ga4 has potential
      for application in novel magnetic memory devices, such as the magnetic components
      of tunneling magnetoresistance spintronics devices.

PMID- 29588461
TI  - Diffusion tensor tractography of the mammillothalamic tract in the human brain
      using a high spatial resolution DTI technique.
AB  - The mammillary bodies as part of the hypothalamic nuclei are in the central
      limbic circuitry of the human brain. The mammillary bodies are shown to be
      directly or indirectly connected to the amygdala, hippocampus, and thalami as the
      major gray matter structures of the human limbic system. Although it is not
      primarily considered as part of the human limbic system, the thalamus is shown to
      be involved in many limbic functions of the human brain. The major direct
      connection of the thalami with the hypothalamic nuclei is known to be through the
      mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in
      memory functions, diffusion tensor imaging may be helpful in better visualizing
      the surgical anatomy of this pathway noninvasively. This study aimed to
      investigate the utility of high spatial resolution diffusion tensor tractography
      for mapping the trajectory of the mammillothalamic tract in the human brain.
      Fifteen healthy adults were studied after obtaining written informed consent. We
      used high spatial resolution diffusion tensor imaging data at 3.0 T. We
      delineated, for the first time, the detailed trajectory of the mammillothalamic
      tract of the human brain using deterministic diffusion tensor tractography.

PMID- 29588464
TI  - Rydberg interaction induced enhanced excitation in thermal atomic vapor.
AB  - We present the experimental demonstration of interaction induced enhancement in
      Rydberg excitation or Rydberg anti-blockade in thermal atomic vapor. We have used
      optical heterodyne detection technique to measure Rydberg population due to two
      photon excitation to the Rydberg state. The anti-blockade peak which doesn't
      satisfy the two-photon resonant condition is observed along with the usual two
      photon resonant peak which can't be explained using the model with non
      interacting three-level atomic system. A model involving two interacting atoms is
      formulated for thermal atomic vapor using the dressed states of three-level
      atomic system to explain the experimental observations. A non-linear dependence
      of vapor density is observed for the anti-blockade peak which also increases with
      increase in principal quantum number of the Rydberg state. A good agreement is
      found between the experimental observations and the proposed interacting model.
      Our result implies possible applications towards quantum logic gates using
      Rydberg anti-blockade in thermal atomic vapor.

PMID- 29588463
TI  - Combining targeted panel-based resequencing and copy-number variation analysis
      for the diagnosis of inherited syndromic retinopathies and associated
      ciliopathies.
AB  - Inherited syndromic retinopathies are a highly heterogeneous group of diseases
      that involve retinal anomalies and systemic manifestations. They include retinal
      ciliopathies, other well-defined clinical syndromes presenting with retinal
      alterations and cases of non-specific multisystemic diseases. The heterogeneity
      of these conditions makes molecular and clinical characterization of patients
      challenging in daily clinical practice. We explored the capacity of targeted
      resequencing and copy-number variation analysis to improve diagnosis of a
      heterogeneous cohort of 47 patients mainly comprising atypical cases that did not
      clearly fit a specific clinical diagnosis. Thirty-three likely pathogenic
      variants were identified in 18 genes (ABCC6, ALMS1, BBS1, BBS2, BBS12, CEP41,
      CEP290, IFT172, IFT27, MKKS, MYO7A, OTX2, PDZD7, PEX1, RPGRIP1, USH2A, VPS13B,
      and WDPCP). Molecular findings and additional clinical reassessments made it
      possible to accurately characterize 14 probands (30% of the total). Notably,
      clinical refinement of complex phenotypes was achieved in 4 cases, including 2 de
      novo OTX2-related syndromes, a novel phenotypic association for the ciliary CEP41
      gene, and the co-existence of biallelic USH2A variants and a Koolen-de-Vries
      syndrome-related 17q21.31 microdeletion. We demonstrate that combining next
      generation sequencing and CNV analysis is a comprehensive and useful approach to
      unravel the extensive phenotypic and genotypic complexity of inherited syndromic
      retinopathies.

PMID- 29588465
TI  - MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of
      Arc/Arg3.1.
AB  - Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic
      membrane is a key determinant of the strength of excitatory neurotransmission,
      and is thought to underlie learning and memory. The transcription factor MEF2 is
      a negative regulator of memory in vivo, in part by regulating trafficking of the
      AMPAR subunit GluA2, but the molecular mechanisms behind this have not been
      established. Here we show, via knockdown of endogenous MEF2A in primary neuronal
      culture, that MEF2A is specifically required for Group I metabotropic glutamate
      receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR
      expression or trafficking under basal conditions. Furthermore, this process
      occurs independently of changes in expression of Arc/Arg3.1, a previously
      characterised MEF2 transcriptional target and mediator of mGluR-dependent long
      term depression. These data demonstrate a novel MEF2A-dependent mechanism for the
      regulation of activity-dependent AMPAR trafficking.

PMID- 29588466
TI  - Canagliflozin inhibits interleukin-1beta-stimulated cytokine and chemokine
      secretion in vascular endothelial cells by AMP-activated protein kinase-dependent
      and -independent mechanisms.
AB  - Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2
      (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported
      beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect
      cardiovascular tissues, however, remains unclear. We have previously reported
      that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase
      (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti
      inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors
      attenuated inflammatory signalling in cultured human endothelial cells.
      Incubation with clinically-relevant concentrations of canagliflozin, but not
      empagliflozin or dapagliflozin activated AMPK and inhibited IL-1beta-stimulated
      adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte
      chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated
      by expression of dominant-negative AMPK and was mimicked by the direct AMPK
      activator, A769662. Stimulation of cells with either canagliflozin or A769662 had
      no effect on IL-1beta-stimulated cell surface levels of adhesion molecules or
      nuclear factor-kappaB signalling. Despite these identical effects of
      canagliflozin and A769662, IL-1beta-stimulated IL-6/MCP-1 mRNA was inhibited by
      canagliflozin, but not A769662, whereas IL-1beta-stimulated c-jun N-terminal
      kinase phosphorylation was inhibited by A769662, but not canagliflozin. These
      data indicate that clinically-relevant canagliflozin concentrations directly
      inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK
      dependent and -independent mechanisms without affecting early IL-1beta
      signalling.

PMID- 29588467
TI  - Intriguingly high thermal conductivity increment for CuO nanowires contained
      nanofluids with low viscosity.
AB  - Nanofluids offer the exciting new possibilities to enhance heat transfer
      performance. In this paper, experimental and theoretical investigations have been
      conducted to determine the effect of CuO nanowires on the thermal conductivity
      and viscosity of dimethicone based nanofluids. The CuO nanowires were prepared
      through a thermal oxidation method, and the analysis indicated that the as
      prepared CuO nanowires had high purity, monocrystalline with a monoclinic
      structure and large aspect ratio compared to CuO nanospheres. The experimental
      data show that the thermal conductivity of the nanofluids increases with the
      volume fraction of CuO nanowires or nanospheres, with a nearly linear
      relationship. For the nanofluid with the addition of 0.75 vol.% CuO nanowires,
      the thermal conductivity enhancement is up to 60.78%, which is much higher than
      that with spherical CuO nanoparticles. The nanofluids exhibit typical Newtonian
      behavior, and the measured viscosity of CuO nanowires contained nanofluids were
      found only 6.41% increment at the volume fraction of 0.75%. It is attractive in
      enhanced heat transfer for application. The thermal conductivity and viscosity of
      CuO nanofluids were further calculated and discussed by comparing our
      experimental results with the classic theoretical models. The mechanisms of
      thermal conductivity and viscosity about nanofluids were also discussed in
      detail.

PMID- 29588468
TI  - Ras hyperactivation versus overexpression: Lessons from Ras dynamics in Candida
      albicans.
AB  - Ras signaling in response to environmental cues is critical for cellular
      morphogenesis in eukaryotes. This signaling is tightly regulated and its
      activation involves multiple players. Sometimes Ras signaling may be
      hyperactivated. In C. albicans, a human pathogenic fungus, we demonstrate that
      dynamics of hyperactivated Ras1 (Ras1G13V or Ras1 in Hsp90 deficient strains) can
      be reliably differentiated from that of normal Ras1 at (near) single molecule
      level using fluorescence correlation spectroscopy (FCS). Ras1 hyperactivation
      results in significantly slower dynamics due to actin polymerization. Activating
      actin polymerization by jasplakinolide can produce hyperactivated Ras1 dynamics.
      In a sterol-deficient hyperfilamentous GPI mutant of C. albicans too, Ras1
      hyperactivation results from Hsp90 downregulation and causes actin
      polymerization. Hyperactivated Ras1 co-localizes with G-actin at the plasma
      membrane rather than with F-actin. Depolymerizing actin with cytochalasin D
      results in faster Ras1 dynamics in these and other strains that show Ras1
      hyperactivation. Further, ergosterol does not influence Ras1 dynamics.

PMID- 29588469
TI  - Material Synthesis and Device Aspects of Monolayer Tungsten Diselenide.
AB  - In this paper, we investigate the synthesis of WSe2 by chemical vapor deposition
      and study the current transport and device scaling of monolayer WSe2. We found
      that the device characteristics of the back-gated WSe2 transistors with thick
      oxides are very sensitive to the applied drain bias, especially for transistors
      in the sub-micrometer regime. The threshold voltage, subthreshold swing, and
      extracted field-effect mobility vary with the applied drain bias. The output
      characteristics in the long-channel transistors show ohmic-like behavior, while
      that in the short-channel transistors show Schottky-like behavior. Our
      investigation reveals that these phenomena are caused by the drain-induced
      barrier lowering (short-channel effect). For back-gated WSe2 transistors with 280
      nm oxide, the short-channel effect appears when the channel length is shorter
      than 0.4 um. This extremely long electrostatic scaling length is due to the thick
      back-gate oxides. In addition, we also found that the hydrogen flow rate and the
      amount of WO3 precursor play an important role in the morphology of the WSe2. The
      hole mobility of the monolayer WSe2 is limited by Columbic scattering below 250
      K, while it is limited by phonon scattering above 250 K. These findings are very
      important for the synthesis of WSe2 and accurate characterization of the
      electronic devices based on 2D materials.

PMID- 29588470
TI  - Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal
      cerebral ischemia.
AB  - Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases
      from arachidonic acid, and their rapid metabolism is mainly through soluble
      epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti
      apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or
      at the onset of stroke is protective, but the effects of post-treatment at
      reperfusion, when inflammation is augmented, has not been as well studied. We
      tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4
      yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses
      inflammation and protects the brain when administered at reperfusion. Vehicle or
      1 mg/kg TPPU was administered at reperfusion after 90 minutes of focal ischemia
      and again 24 hours later. Protein expression and activity of sEH increased after
      reperfusion and activity was decreased by TPPU administration. TPPU decreased
      infarct volume by 50%, reduced neurologic deficits and improved performance on
      sensorimotor tasks. Furthermore, TPPU significantly lowered the mRNA expression
      of interleukin-1beta by 3.5-fold and tumor necrosis factor-alpha by 2.2-fold,
      increased transforming growth factor-beta mRNA by 1.8-fold, and augmented
      immunostaining of vascular endothelial growth factor in peri-infarct cortex.
      Thus, inhibition of sEH at reperfusion significantly reduces infarction and
      improves sensorimotor function, possibly by suppressing early proinflammatory
      cytokines and promoting reparative cytokines and growth factors.

PMID- 29588471
TI  - Discovery of a highly selective JAK3 inhibitor for the treatment of rheumatoid
      arthritis.
AB  - Janus tyrosine kinase 3 (JAK3) is expressed in lymphoid cells and is involved in
      the signalling of T cell functions. The development of a selective JAK3 inhibitor
      has been shown to have a potential benefit in the treatment of autoimmune
      disorders. In this article, we developed the 4-aminopiperidine-based compound
      RB1, which was highly selective for JAK3 inhibition, with an IC50 of value of 40
      nM, but did not inhibit JAK1, JAK2 or tyrosine kinase 2 (TYK2) at concentrations
      up to 5 uM. Furthermore, RB1 also exhibited favourable selectivity against a
      panel of representative kinases. In a battery of cytokine-stimulated cell-based
      assays, this potent inhibitor of JAK3 activity with good selectivity against
      other kinases could potently inhibit JAK3 activity over the activity of JAK1 or
      JAK2 (over at least 100-fold). A combination of liquid chromatography-mass
      spectrometry (LC-MS) experiments validated that RB1 covalently modified the
      unique cysteine 909 residue in JAK3. In vivo, RB1 exerted significantly improved
      pathology in the joints of a collagen-induced arthritis mouse model. The
      reasonable pharmacokinetics properties (F = 72.52%, T1/2 = 14.6 h) and favourable
      results of toxicology experiments (LD50 > 2 g/kg) suggest that RB1 has the
      potential to be an efficacious treatment for RA.

PMID- 29588472
TI  - Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause
      mortality: 20 years follow-up in patients after hip or knee replacement.
AB  - : Osteoarthritis (OA) is a common musculoskeletal disorder and occur in different
      patterns. However, its impact on long-term all-cause-mortality is inconclusive.
      STUDY AIMS: Investigate 20-year all-cause-mortality in patients with hip/knee
      arthroplasty (recruited 1995/1996, N = 809) from the Ulm Osteoarthritis Study
      cohort, in comparison to general population. Furthermore, to enlighten the
      triangle between baseline life-style and cardio-metabolic risk factors,
      phenotypic OA-patterns (laterality, generalization, cause) and all-cause
      mortality. Mortality was assessed during 20 years follow-up. Standardized
      mortality ratios (SMR), adjusted odds ratios and hazard ratios (aHR) were
      calculated. After five years cohort-mortality was reduced compared to the general
      population, however 20 years later assimilated (SMR = 1.11; 95%-CI 0.73-1.49). OA
      patterns were associated with age, cholesterol, and overweight/obesity. In
      comparison to primary OA decreased mortality was observed for patients with
      secondary OA (aHR = 0.76; 95%-CI 0.61-0.95) adjusted for age, smoking,
      overweight/obesity, diabetes, hypertension, cardiac insufficiency, uric acid, and
      lower cholesterol. There was no increased mortality in patients after 20 years
      follow-up compared to general population. Significantly decreased mortality in
      secondary compared to primary OA suggests a subtype-specific involvement of
      systemic co-factors in determination of all-cause-mortality. Because cardio
      metabolic risk factors were associated with increased risk of bilateral OA and
      lower long-term survival, those risk factors should be consequently targeted in
      OA-patients.

PMID- 29588473
TI  - Spatial-temporal profiling of prodiginines and serratamolides produced by
      endophytic Serratia marcescens harbored in Maytenus serrata.
AB  - An endophytic bacterium, Serratia marcescens MSRBB2, isolated from inner bark of
      a Cameroonian Maytenus serrata plant, was subjected to the OSMAC (One Strain Many
      Compounds) approach and metabolic profiling using HPLC-HRMSn. We identified 7
      prodiginines along with 26 serratamolides. Their biosynthetic pathways were
      elucidated by feeding with labeled precursors in combination with HRMSn. Dual
      culture confrontation/restriction assays of the bacterial endophyte were devised
      with coexisting fungal endophytes (Pestalotiopsis virgatula, Aspergillus
      caesiellus and Pichia spp.) as well as with unrelated, non-endophytic fungi
      belonging to the same genera. The assays were combined with scanning electron
      microscopy (SEM) as well as matrix-assisted laser desorption ionization imaging
      high-resolution mass spectrometry (MALDI-imaging-HRMS) for visualizing, both in
      high spatial and temporal resolution, the distribution and interplay of the
      compounds during microbial interactions. We demonstrated the effect of
      prodigiosin produced by endophytic S. marcescens MSRBB2 as an allelochemical that
      specifically inhibits coexisting endophytic fungi. Our results provide new
      insights into the physiological and ecological relevance of prodiginines and
      serratamolides within the context of allelopathy and chemical defense interaction
      occurring between coexisting endophytes harbored in M. serrata.

PMID- 29588474
TI  - Schramm-Loewner evolution and perimeter of percolation clusters of correlated
      random landscapes.
AB  - Motivated by the fact that many physical landscapes are characterized by long
      range height-height correlations that are quantified by the Hurst exponent H, we
      investigate the statistical properties of the iso-height lines of correlated
      surfaces in the framework of Schramm-Loewner evolution (SLE). We show numerically
      that in the continuum limit the external perimeter of a percolating cluster of
      correlated surfaces with H ? [-1, 0] is statistically equivalent to SLE curves.
      Our results suggest that the external perimeter also retains the Markovian
      properties, confirmed by the absence of time correlations in the driving function
      and the fact that the latter is Gaussian distributed for any specific time. We
      also confirm that for all H the variance of the winding angle grows
      logarithmically with size.

PMID- 29588475
TI  - NF-kB2 Genetic Variations are Significantly Associated with Non-Small Cell Lung
      Cancer Risk and Overall Survival.
AB  - During the last decade, a growing number of publications implicate NF-kB2 in
      NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single
      nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and
      their association with NF-kB2 protein and mRNA levels. Our data show that TT
      (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with
      an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively).
      Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was
      associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028,
      respectively), especially among patients with stages III/IV, who had worse 2, 3
      and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In
      chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also
      associated with worse 2- and 3-year survival compared to G allele carriers (P =
      0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with
      survival outcome of stage I and II patients (P = 0.031 and P = 0.006,
      respectively). Interestingly, amongst the patients who developed metastases, A
      allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316
      was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as
      well as with tumor maximum diameter (P = 0.025). Overall, this study suggests
      that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment
      response and in clinical outcome.

PMID- 29588476
TI  - Sequence-dependent catalytic regulation of the SpoIIIE motor activity ensures
      directionality of DNA translocation.
AB  - Transport of cellular cargo by molecular motors requires directionality to ensure
      proper biological functioning. During sporulation in Bacillus subtilis,
      directionality of chromosome transport is mediated by the interaction between the
      membrane-bound DNA translocase SpoIIIE and specific octameric sequences (SRS).
      Whether SRS regulate directionality by recruiting and orienting SpoIIIE or by
      simply catalyzing its translocation activity is still unclear. By using atomic
      force microscopy and single-round fast kinetics translocation assays we
      determined the localization and dynamics of diffusing and translocating SpoIIIE
      complexes on DNA with or without SRS. Our findings combined with mathematical
      modelling revealed that SpoIIIE directionality is not regulated by protein
      recruitment to SRS but rather by a fine-tuned balance among the rates governing
      SpoIIIE-DNA interactions and the probability of starting translocation modulated
      by SRS. Additionally, we found that SpoIIIE can start translocation from non
      specific DNA, providing an alternative active search mechanism for SRS located
      beyond the exploratory length defined by 1D diffusion. These findings are
      relevant in vivo in the context of chromosome transport through an open channel,
      where SpoIIIE can rapidly explore DNA while directionality is modulated by the
      probability of translocation initiation upon interaction with SRS versus non
      specific DNA.

PMID- 29588477
TI  - Machine learning approaches for large scale classification of produce.
AB  - The analysis and identification of different attributes of produce such as
      taxonomy, vendor, and organic nature is vital to verifying product authenticity
      in a distribution network. Though a variety of analysis techniques have been
      studied in the past, we present a novel data-centric approach to classifying
      produce attributes. We employed visible and near infrared (NIR) spectroscopy on
      over 75,000 samples across several fruit and vegetable varieties. This yielded
      0.90-0.98 and 0.98-0.99 classification accuracies for taxonomy and farmer
      classes, respectively. The most significant factors in the visible spectrum were
      variations in the produce color due to chlorophyll and anthocyanins. In the
      infrared spectrum, we observed that the varying water and sugar content levels
      were critical to obtaining high classification accuracies. High quality spectral
      data along with an optimal tuning of hyperparameters in the support vector
      machine (SVM) was also key to achieving high classification accuracies. In
      addition to demonstrating exceptional accuracies on test data, we explored
      insights behind the classifications, and identified the highest performing
      approaches using cross validation. We presented data collection guidelines,
      experimental design parameters, and machine learning optimization parameters for
      the replication of studies involving large sample sizes.

PMID- 29588478
TI  - Ikaros family zinc finger 1 regulates dendritic cell development and function in
      humans.
AB  - Ikaros family zinc finger 1 (IKZF1) is a haematopoietic transcription factor
      required for mammalian B-cell development. IKZF1 deficiency also reduces
      plasmacytoid dendritic cell (pDC) numbers in mice, but its effects on human DC
      development are unknown. Here we show that heterozygous mutation of IKZF1 in
      human decreases pDC numbers and expands conventional DC1 (cDC1). Lenalidomide, a
      drug that induces proteosomal degradation of IKZF1, also decreases pDC numbers in
      vivo, and reduces the ratio of pDC/cDC1 differentiated from progenitor cells in
      vitro in a dose-dependent manner. In addition, non-classical monocytes are
      reduced by IKZF1 deficiency in vivo. DC and monocytes from patients with IKZF1
      deficiency or lenalidomide-treated cultures secrete less IFN-alpha, TNF and IL
      12. These results indicate that human DC development and function are regulated
      by IKZF1, providing further insights into the consequences of IKZF1 mutation on
      immune function and the mechanism of immunomodulation by lenalidomide.

PMID- 29588479
TI  - Humans significantly metabolize and excrete the mycotoxin deoxynivalenol and its
      modified form deoxynivalenol-3-glucoside within 24 hours.
AB  - For the first time, a comprehensive human intervention study was conducted to
      unravel the urinary excretion profile and metabolism of the fungal metabolite
      deoxynivalenol (DON) and its modified form deoxynivalenol-3-glucoside (DON-3
      glucoside). Twenty volunteers were restricted in consuming cereals and cereal
      based foods for 4 days. At day 3, a single bolus of 1 ug/kg body weight of DON
      and a single bolus of 1 ug/kg body weight of DON-3-glucoside after a washing-out
      period of two months was administered, and a 24-h urine collection was performed.
      The urine was analysed for DON, DON-3-glucoside, 3-ADON, 15-ADON, deepoxy
      deoxynivalenol (DOM-1), deoxynivalenol-3-glucuronide (DON-3-glucuronide) and
      deoxynivalenol-15-glucuronide (DON-15-glucuronide). The urinary biomarker
      analysis revealed that DON and DON-3-glucoside were rapidly absorbed,
      distributed, metabolized and excreted. Sixty-four % of the administered DON and
      58% of DON-3-glucoside was recovered in the urine collected within 24 h. DON-15
      glucuronide was the most prominent urinary biomarker followed by free DON and DON
      3-glucuronide. Moreover, correlations among the presence of DON-15-glucuronide
      and DON-3-glucuronide were observed (within 24 hours (r = 0.61)). The DOM-1
      detected in the urine was higher after the DON-3-glucoside administration. The
      obtained results are imperative to construct a standardized method to estimate
      DON-intake by means of urinary biomarkers.

PMID- 29588480
TI  - Proteins involved in embryo-maternal interaction around the signalling of
      maternal recognition of pregnancy in the horse.
AB  - During maternal recognition of pregnancy (MRP), a conceptus-derived signal leads
      to the persistence of the corpus luteum and the maintenance of gestation. In the
      horse, the nature of this signal remains to be elucidated. Several studies have
      focused on the changes in gene expression during MRP, but little information
      exists at the protein level. The aim of this study was to identify the proteins
      at the embryo-maternal interface around signalling of MRP in the horse (day 13)
      by means of mass spectrometry. A distinct influence of pregnancy was established,
      with 119 proteins differentially expressed in the uterine fluid of pregnant mares
      compared to cyclic mares and with upregulation of several inhibitors of the
      prostaglandin synthesis during pregnancy. By creating an overview of the proteins
      at the embryo-maternal interface in the horse, this study provides a solid
      foundation for further targeted studies of proteins potentially involved in
      embryo-maternal interactions, MRP and pregnancy loss in the horse.

PMID- 29588481
TI  - Comparative genome-wide analysis of extracellular small RNAs from the
      mucormycosis pathogen Rhizopus delemar.
AB  - Rhizopus delemar is an emerging fungal pathogen causing devastating mucormycosis
      in immunocompromised individuals. The organism remains understudied and there are
      urgent needs for new methods of rapid disease diagnosis for timely therapy.
      Extracellular vesicles with encapsulated RNAs have recently been discovered to
      have great potential applications for disease diagnoses and treatments. To
      explore the utilization of ex-RNA in studies of mucormycosis, we have performed
      RNA-Seq of ex-sRNAs from two clinical strains of R. delemar. Approximately 3.3
      and 3.2 million clean reads were obtained from FGSC-9543 and CDC-8219 strains,
      respectively. The median sequence length of the sRNAs was 22 nts, with a minimum
      of 18 and a maximum of 30 nts. Further annotation identified 560 and 526 miRNAs
      from FGSC-9543 and CDC-8219 strains, respectively. miRNA target prediction and
      analysis of GO and KEGG pathways have revealed that the regulation of metabolism,
      secondary metabolite biosynthesis, and two-component system signaling are
      important during growth. We have also validated RNA-Seq by qRT-PCR and Northern
      blotting analysis of randomly selected miRNAs. Our results show that R. delemar
      has a rich reservoir of secreted ex-sRNAs and our studies could facilitate the
      development of improved diagnostic methods as well as elucidating virulence
      mechanisms for R. delemar infection.

PMID- 29588482
TI  - Synthesis of NiMn-LDH Nanosheet@Ni3S2 Nanorod Hybrid Structures for
      Supercapacitor Electrode Materials with Ultrahigh Specific Capacitance.
AB  - One of the key challenges for pseudocapacitive electrode materials with highly
      effective capacitance output and future practical applications is how to
      rationally construct hierarchical and ordered hybrid nanoarchitecture through the
      simple process. Herein, we design and synthesize a novel NiMn-layered double
      hydroxide nanosheet@Ni3S2 nanorod hybrid array supported on porous nickel foam
      via a one-pot hydrothermal method. Benefited from the ultrathin and rough nature,
      the well-defined porous structure of the hybrid array, as well as the synergetic
      effect between NiMn-layered double hydroxide nanosheets and Ni3S2 nanorods, the
      as-fabricated hybrid array-based electrode exhibits an ultrahigh specific
      capacitance of 2703 F g-1 at 3 A g-1. Moreover, the asymmetric supercapacitor
      with this hybrid array as a positive electrode and wood-derived activated carbon
      as a negative electrode demonstrates high energy density (57 Wh Kg-1 at 738 W Kg
      1) and very good electrochemical cycling stability.

PMID- 29588483
TI  - Genome plasticity is governed by double strand break DNA repair in Streptomyces.
AB  - The linear chromosome of the bacterium Streptomyces exhibits a remarkable genetic
      organization with grossly a central conserved region flanked by variable
      chromosomal arms. The terminal diversity co-locates with an intense DNA
      plasticity including the occurrence of large deletions associated to
      circularization and chromosomal arm exchange. These observations prompted us to
      assess the role of double strand break (DSB) repair in chromosome plasticity
      following. For that purpose, DSBs were induced along the chromosome using the
      meganuclease I-SceI. DSB repair in the central region of the chromosome was
      mutagenic at the healing site but kept intact the whole genome structure. In
      contrast, DSB repair in the chromosomal arms was mostly associated to the loss of
      the targeted chromosomal arm and extensive deletions beyond the cleavage sites.
      While homologous recombination occurring between copies of DNA sequences
      accounted for the most part of the chromosome rescue events, Non Homologous End
      Joining was involved in mutagenic repair as well as in huge genome rearrangements
      (i.e. circularization). Further, NHEJ repair was concomitant with the integration
      of genetic material at the healing site. We postulate that DSB repair drives
      genome plasticity and evolution in Streptomyces and that NHEJ may foster
      horizontal transfer in the environment.

PMID- 29588484
TI  - Neurosurgical untethering with or without syrinx drainage results in high patient
      satisfaction and favorable clinical outcome in post-traumatic myelopathy
      patients.
AB  - STUDY DESIGN: Retrospective data collection and patient-reported outcome
      measures. OBJECTIVES: To investigate surgical outcome, complications, and patient
      satisfaction in patients with chronic SCI and symptomatic post-traumatic
      progressive myelopathy (PPM) who underwent neurosurgical untethering and/or
      spinal cord cyst drainage with the aim of preventing further neurological
      deterioration. SETTING: Single-center study at an academic neurosurgery
      department. METHODS: All SCI patients who underwent neurosurgery between 1996 and
      2013 were retrospectively included. All medical charts and the treating surgeon's
      operative reports were reviewed to identify surgical indications, surgical
      technique, and post-operative complications. A questionnaire and an EQ-5D
      instrument were used to assess patient's self-described health status and
      satisfaction at long-term follow-up. RESULTS: Fifty-two patients (43 men, 9
      women) were identified, of whom five were dead and one was lost to follow-up.
      Main indications for surgery were pain (54%), motor (37%), or sensory (8%)
      impairment, and spasticity (2.0%). Overall complications were rare (8%). At
      follow-up, the subjectively perceived outcome was improved in 24 and remained
      unchanged in 21 patients. Thus, the surgical aim was met in 87% of patients. Of
      the 46 eligible patients, 38 responded to the questionnaire of whom 65% were
      satisfied with the surgical results. Patients with cervical lesions were more
      satisfied with the surgical treatment than patients with thoracic/thoracolumbar
      lesions (p = 0.05). CONCLUSIONS: Neurosurgical untethering and/or cyst drainage
      in chronic SCI patients and PPM resulted in a high degree of patient
      satisfaction, particularly in cervical SCI patients with minimal complications.

PMID- 29588485
TI  - Association between serum uric acid and cardiovascular risk in nonhypertensive
      and nondiabetic individuals: The Taiwan I-Lan Longitudinal Aging Study.
AB  - Serum uric acid level is a risk factor for cardiovascular disease (CVD). However,
      whether it is an independent risk factor or not remains controversial. We
      analyzed the association between serum uric acid level and cardiovascular risk.
      In total, 973 nonhypertensive and nondiabetic participants in the I-Lan
      Longitudinal Aging Study were eligible for this study. Subjects were divided into
      tertiles according to uric acid levels. The 10-year cardiovascular risk was
      calculated using Framingham risk score (FRS). Study subjects in the highest
      tertile of serum uric acid level were older, more likely to be male, and had
      higher systolic blood pressure, body mass index, carotid artery intima-media
      thickness and serum triglyceride, high-sensitivity C-reactive protein, and low
      density lipoprotein cholesterol levels and lower serum high-density lipoprotein
      cholesterol levels (all p < 0.05). Subjects in the highest tertile had
      significantly higher FRS (p < 0.001). After adjusting for other risk factors,
      serum uric acid level remained associated significantly with the FRS (p < 0.05).
      In binary logistic regression analysis, the serum uric acid level was an
      independent predictive factor for high (>=20%) FRS (odds ratio 1.33, 95%
      confidence interval 1.10-1.68). These findings warrant attention to this
      cardiovascular risk factor in apparently healthy adults.

PMID- 29588486
TI  - Structural prediction of host-guest structure in lithium at high pressure.
AB  - Ab initio random structure searching (AIRSS) technique is used to identify the
      high-pressure phases of lithium (Li). We proposed the transition mechanism from
      the fcc to host-guest (HG) structures at finite temperature and high pressure.
      This complex structural phase transformation has been calculated using ab initio
      lattice dynamics with finite displacement method which confirms the dynamical
      harmonic stabilization of the HG structure. The electron distribution between the
      host-host atoms has also been investigated by electron localization function
      (ELF). The strongly localized electron of p bond has led to the stability of the
      HG structure. This remarkable result put the HG structure to be a common high
      pressure structure among alkali metals.

PMID- 29588487
TI  - Trophoblast-derived CXCL16 induces M2 macrophage polarization that in turn
      inactivates NK cells at the maternal-fetal interface.
AB  - Decidual macrophages (dMPhi) are distinct from the conventional macrophages
      present in other tissues and express M2 macrophage markers, but the molecular
      mechanisms of formation and the roles of M2 MPhi during pregnancy have not been
      completely elucidated. The crosstalk between decidual natural killer cells (dNK)
      and dMPhi plays an important role in the maintenance of maternal-fetal immune
      tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces
      the polarization of human M2 macrophages. The M2 MPhi polarized by CXCL16 exhibit
      decreased interleukin-15 production, which facilitates the inactivation of NK
      cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2
      MPhi. The data shown in the present study provide evidence to support the
      hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involved
      in decidual M2 MPhi polarization, which in turn regulates the killing ability of
      NK cells, thereby contributing to the homeostatic and immune-tolerant milieu
      required for successful fetal development.

PMID- 29588488
TI  - Dynamic analysis of the interactions between Si/SiO2 quantum dots and
      biomolecules for improving applications based on nano-bio interfaces.
AB  - Due to their outstanding properties, quantum dots (QDs) received a growing
      interest in the biomedical field, but it is of major importance to investigate
      and to understand their interaction with the biomolecules. We examined the
      stability of silicon QDs and the time evolution of QDs - protein corona formation
      in various biological media (bovine serum albumin, cell culture medium without or
      supplemented with 10% fetal bovine serum-FBS). Changes in the secondary structure
      of BSA were also investigated over time. Hydrodynamic size and zeta potential
      measurements showed an evolution in time indicating the nanoparticle-protein
      interaction. The protein corona formation was also dependent on time, albumin
      adsorption reaching the peak level after 1 hour. The silicon QDs adsorbed an
      important amount of FBS proteins from the first 5 minutes of incubation that was
      maintained for the next 8 hours, and diminished afterwards. Under protein-free
      conditions the QDs induced cell membrane damage in a time-dependent manner,
      however the presence of serum proteins attenuated their hemolytic activity and
      maintained the integrity of phosphatidylcholine layer. This study provides useful
      insights regarding the dynamics of BSA adsorption and interaction of silicon QDs
      with proteins and lipids, in order to understand the role of QDs biocorona.

PMID- 29588489
TI  - Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B
      patients with normal or mildly elevated alanine transaminase levels.
AB  - We aimed to evaluate the diagnostic accuracy of liver stiffness measurement (LSM)
      in 188 chronic hepatitis B (CHB) patients with alanine transaminase (ALT) <=
      twice the upper limit of normal (ULN). Liver fibrosis was staged using METAVIR
      scoring system. Define significant fibrosis as F2-F4, severe fibrosis as F3-F4,
      and cirrhosis as F4. To predict F2-F4, the AUROC of LSM was higher than that of
      APRI (0.86 vs 0.73, p = 0.001) and FIB-4 (0.86 vs 0.61, p < 0.001). To predict
      F4, the AUROC of LSM was also higher than that of APRI (0.93 vs 0.77, p = 0.012)
      and FIB-4 (0.93 vs 0.64, p < 0.001). Patients with ALT levels 1-2 ULN had higher
      cut-off values than patients with normal ALT levels for the diagnosis of F2-F4
      (6.5 vs 6 kPa) and F4 (10.2 vs 7.8 kPa). Using cut-off values regardless of ALT
      levels, the diagnostic accuracy of LSM was 81% for F2-F4, and 89% for F4.
      Applying ALT-stratified cut-off values, the diagnostic accuracy of LSM was 82%
      for F2-F4, and 86% for F4. In conclusion, LSM is a reliable noninvasive test for
      the diagnosis of liver fibrosis. Applying ALT-stratified cut-off values did not
      enhance diagnostic accuracy of LSM in CHB patients with ALT <= 2 ULN.

PMID- 29588490
TI  - LentiPro26: novel stable cell lines for constitutive lentiviral vector
      production.
AB  - Lentiviral vectors (LVs) are excellent tools to promote gene transfer and stable
      gene expression. Their potential has been already demonstrated in gene therapy
      clinical trials for the treatment of diverse disorders. For large scale LV
      production, a stable producer system is desirable since it allows scalable and
      cost-effective viral productions, with increased reproducibility and safety.
      However, the development of stable systems has been challenging and time
      consuming, being the selection of cells presenting high expression levels of Gag
      Pro-Pol polyprotein and the cytotoxicity associated with some viral components,
      the main limitations. Hereby is described the establishment of a new LV producer
      cell line using a mutated less active viral protease to overcome potential
      cytotoxic limitations. The stable transfection of bicistronic expression
      cassettes with re-initiation of the translation mechanism enabled the generation
      of LentiPro26 packaging populations supporting high titers. Additionally, by
      skipping intermediate clone screening steps and performing only one final clone
      screening, it was possible to save time and generate LentiPro26-A59 cell line,
      that constitutively produces titers above 106 TU.mL-1.day-1, in less than six
      months. This work constitutes a step forward towards the development of improved
      LV producer cell lines, aiming to efficiently supply the clinical expanding gene
      therapy applications.

PMID- 29588491
TI  - Identification of inhibitors regulating cell proliferation and FUS-DDIT3
      expression in myxoid liposarcoma using combined DNA, mRNA, and protein analyses.
AB  - FUS-DDIT3 belongs to the FET (FUS, EWSR1, and TAF15) family of fusion oncogenes,
      which collectively are considered to be key players in tumor development. Even
      though over 90% of all myxoid liposarcomas (MLS) have a FUS-DDIT3 gene fusion,
      there is limited understanding of the signaling pathways that regulate its
      expression. In order to study cell proliferation and FUS-DDIT3 regulation at mRNA
      and protein levels, we first developed a direct cell lysis approach that allows
      DNA, mRNA, and protein to be analyzed in the same sample using quantitative PCR,
      reverse transcription quantitative qPCR and proximity ligation assay,
      respectively. We screened 70 well-characterized kinase inhibitors and determined
      their effects on cell proliferation and expression of FUS-DDIT3 and FUS at both
      mRNA and protein levels in the MLS 402-91 cell line, where twelve selected
      inhibitors were evaluated further in two additional MLS cell lines. Both FUS
      DDIT3 and FUS mRNA expression correlated with cell proliferation and both
      transcripts were co-regulated in most conditions, indicating that the common 5'
      FUS promotor is important in transcriptional regulation. In contrast, FUS-DDIT3
      and FUS protein levels displayed more cell line dependent expression.
      Furthermore, most JAK inhibitors caused FUS-DDIT3 downregulation at both mRNA and
      protein levels. In conclusion, defining factors that regulate FUS-DDIT3
      expression opens new means to understand MLS development at the molecular level.

PMID- 29588493
TI  - Bilateral geochemical asymmetry in the Karoo large igneous province.
AB  - In the Karoo large igneous province, the geochemical assessment of mantle source
      variability and structure is hampered by probable crustal contamination
      overprinting of compositionally diverse flood basalts. Mantle source
      characteristics have been defined only for exceptional, primitive rock types.
      Here I use a compiled dataset for over 800 samples to demonstrate that the
      abundance of Nb relative to Zr, Ti, and Y provides a useful geochemical tracer of
      mantle sources for variably contaminated rock types of the Karoo province.
      Variations in the relative abundance of Nb reveal emplacement of distinctive, Nb
      undepleted and Nb-depleted magmas in the North Karoo and South Karoo sub
      provinces, respectively, and clarify correlation between flood basalts and
      previously proposed mantle source components. Judging from plate tectonic
      reconstructions and the compositions of plausible mantle source components, the
      geochemical bilateral asymmetry in Karoo may reflect tapping of contrasting plume
      and upper mantle reservoirs in the two sub-provinces.

PMID- 29588492
TI  - SFTS phlebovirus promotes LC3-II accumulation and nonstructural protein of SFTS
      phlebovirus co-localizes with autophagy proteins.
AB  - Autophagy is essential for eukaryotic cell homeostasis and can perform both anti
      viral and pro-viral roles depending on the kinds of viruses, cell types and cell
      environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a
      newly discovered tick-borne virus in the Phenuiviridae family that causes a
      severe hemorrhagic fever disease in East Asia. In this study we determined
      interactions between SFTSV and autophagy. Our results showed that LC3-II
      (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h
      to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use
      of E64d and pepstatin A did not affect the expression of LC3-II protein, which
      indicated that the increased LC3-II may be the result of inhibition of autophagic
      degradation caused by SFTSV infection. However, knockdown of LC3B promotes SFTSV
      replication, which indicated a negative role of LC3B protein in SFTSV
      replication. We also detected co-localization of SFTSV non-structure (NSs)
      protein with LC3B, p62 and Lamp2b respectively in SFTSV infected Vero cells,
      which indicated the possibility of selective autophagy or chaperone-mediated
      autophagy involving in SFTSV infection. Our results indicated that SFTSV
      infection promotes LC3 accumulation and several proteins of the autophagy pathway
      co-localize with NSs protein during SFTSV infection.

PMID- 29588494
TI  - Global negative effects of nitrogen deposition on soil microbes.
AB  - Soil microbes comprise a large portion of the genetic diversity on Earth and
      influence a large number of important ecosystem processes. Increasing atmospheric
      nitrogen (N) deposition represents a major global change driver; however, it is
      still debated whether the impacts of N deposition on soil microbial biomass and
      respiration are ecosystem-type dependent. Moreover, the extent of N deposition
      impacts on microbial composition remains unclear. Here we conduct a global meta
      analysis using 1408 paired observations from 151 studies to evaluate the
      responses of soil microbial biomass, composition, and function to N addition. We
      show that nitrogen addition reduced total microbial biomass, bacterial biomass,
      fungal biomass, biomass carbon, and microbial respiration. Importantly, these
      negative effects increased with N application rate and experimental duration.
      Nitrogen addition reduced the fungi to bacteria ratio and the relative abundances
      of arbuscular mycorrhizal fungi and gram-negative bacteria and increased gram
      positive bacteria. Our structural equation modeling showed that the negative
      effects of N application on soil microbial abundance and composition led to
      reduced microbial respiration. The effects of N addition were consistent across
      global terrestrial ecosystems. Our results suggest that atmospheric N deposition
      negatively affects soil microbial growth, composition, and function across all
      terrestrial ecosystems, with more pronounced effects with increasing N deposition
      rate and duration.

PMID- 29588495
TI  - Drinking water microbiome assembly induced by water stagnation.
AB  - What happens to tap water when you are away from home? Day-to-day water
      stagnation in building plumbing can potentially result in water quality
      deterioration (e.g., lead release or pathogen proliferation), which is a major
      public health concern. However, little is known about the microbial ecosystem
      processes in plumbing systems, hindering the development of biological monitoring
      strategies. Here, we track tap water microbiome assembly in situ, showing that
      bacterial community composition changes rapidly from the city supply following ~6
      day stagnation, along with an increase in cell count from 103 cells/mL to upwards
      of 7.8 * 105 cells/mL. Remarkably, bacterial community assembly was highly
      reproducible in this built environment system (median Spearman correlation
      between temporal replicates = 0.78). Using an island biogeography model, we show
      that neutral processes arising from the microbial communities in the city water
      supply (i.e., migration and demographic stochasticity) explained the island
      community composition in proximal pipes (Goodness-of-fit = 0.48), yet declined as
      water approached the faucet (Goodness-of-fit = 0.21). We developed a size-effect
      model to simulate this process, which indicated that pipe diameter drove these
      changes by mediating the kinetics of hypochlorite decay and cell detachment,
      affecting selection, migration, and demographic stochasticity. Our study
      challenges current water quality monitoring practice worldwide which ignore
      biological growth in plumbing, and suggests the island biogeography model as a
      useful framework to evaluate building water system quality.

PMID- 29588496
TI  - Transcriptome-wide mapping of signaling pathways and early immune responses in
      lumpfish leukocytes upon in vitro bacterial exposure.
AB  - We performed RNA sequencing, identified components of the immune system and
      mapped early immune responses of lumpfish (Cyclopterus lumpus) leukocytes
      following in vitro exposure to the pathogenic bacterium Vibrio anguillarum O1.
      This is the first characterization of immune molecules in lumpfish at the gene
      level. In silico analyses revealed that genes encoding proteins involved in
      pathogen recognition, cell signaling and cytokines in mammals and teleosts are
      conserved in lumpfish. Unique molecules were also identified. Pathogen
      recognition components include 13 TLRs, several NLRs and complement factors.
      Transcriptome-wide analyses of immune responses 6 and 24 hours post bacterial
      exposure revealed differential expression of 9033 and 15225 genes, respectively.
      These included TLR5S, IL-1beta, IL-8, IL-6, TNFalpha, IL-17A/F3, IL-17C and
      several components of the complement system. The data generated will be valuable
      for comparative studies and make an important basis for further functional
      analyses of immune and pathogenicity mechanisms. Such knowledge is also important
      for design of immunoprophylactic measures in lumpfish, a species of fish now
      farmed intensively for use as cleaner-fish in Atlantic salmon (Salmo salar)
      aquaculture.

PMID- 29588499
TI  - Another reason to encourage psychosocial risk assessment in hematopoietic cell
      transplantation.

PMID- 29588498
TI  - Topological estimation of signal flow in complex signaling networks.
AB  - In a cell, any information about extra- or intra-cellular changes is transferred
      and processed through a signaling network and dysregulation of signal flow often
      leads to disease such as cancer. So, understanding of signal flow in the
      signaling network is critical to identify drug targets. Owing to the development
      of high-throughput measurement technologies, the structure of a signaling network
      is becoming more available, but detailed kinetic parameter information about
      molecular interactions is still very limited. A question then arises as to
      whether we can estimate the signal flow based only on the structure information
      of a signaling network. To answer this question, we develop a novel algorithm
      that can estimate the signal flow using only the topological information and
      apply it to predict the direction of activity change in various signaling
      networks. Interestingly, we find that the average accuracy of the estimation
      algorithm is about 60-80% even though we only use the topological information. We
      also find that this predictive power gets collapsed if we randomly alter the
      network topology, showing the importance of network topology. Our study provides
      a basis for utilizing the topological information of signaling networks in
      precision medicine or drug target discovery.

PMID- 29588497
TI  - Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral
      delivery of CRISPR/Cas9.
AB  - Serum deficiency diseases such as alpha-1-antitrypsin deficiency are
      characterized by reduced function of serum proteins, caused by deleterious
      genetic mutations. These diseases are promising targets for genetic
      interventions. Gene therapies using viral vectors have been used to introduce
      correct copies of the disease-causing gene in preclinical and clinical studies.
      However, these studies highlighted that disease-alleviating gene expression is
      lost over time. Integration into a specific chromosomal site could provide
      lasting therapeutic expression to overcome this major limitation. Additionally,
      targeted integration could avoid detrimental mutagenesis associated with
      integrative vectors, such as tumorigenesis or functional gene perturbation. To
      test if adenoviral vectors can facilitate long-term gene expression through
      targeted integration, we somatically incorporated the human alpha-1-antitrypsin
      gene into the ROSA26 "safe harbor" locus in murine livers, using CRISPR/Cas9. We
      found adenoviral-mediated delivery of CRISPR/Cas9 achieved gene editing outcomes
      persisting over 200 days. Furthermore, gene knock-in maintained greater levels of
      the serum protein than provided by episomal expression. Importantly, our "knock
      in" approach is generalizable to other serum proteins and supports in vivo cDNA
      replacement therapy to achieve stable gene expression.

PMID- 29588500
TI  - Socioeconomic and health system factors associated with lower utilization of
      hematopoietic cell transplantation in older patients with acute myeloid leukemia.
AB  - Receipt of hematopoietic cell transplantation (HCT) can improve overall survival
      in older patients with intermediate or high-risk acute myeloid leukemia (AML);
      however, utilization of HCT is poor. It is important to understand the factors
      that affect the receipt of HCT in a real-world setting among the older patients.
      We utilized the National Cancer Database to determine receipt of HCT in older
      patients (61-75 years) with intermediate or high-risk AML reported between 2003
      and 2012. Multivariate logistic regression analysis was used to determine factors
      associated with receipt of HCT. Only 5.5% of older patients (n = 17,555)
      underwent HCT. Factors associated with a lower likelihood of receiving HCT
      included receipt of care in a non-academic hospital, race other than white, older
      age, Charlson comorbidity score of >=1, uninsured status, Medicaid or Medicare
      insurance, and lower educational status. The receipt of HCT in older patients is
      low and varies based on biological as well as non-biologic factors, such as
      hospital type, insurance, and educational status. Nationwide efforts to improve
      access to HCT for appropriate patients are necessary.

PMID- 29588501
TI  - Lumenal exposed regions of the D1 protein of PSII are long enough to be degraded
      by the chloroplast Deg1 protease.
AB  - Degradation of the D1 protein of photosystem II (PSII) reaction center is a pre
      requisite for the repair cycle from photoinhibition. Two types of thylakoid
      proteases, FtsH and Deg, have been demonstrated to participate in this process.
      However, the location of the proteolytic sites of the lumenal Deg1 protease
      within its internal sphere raised the question whether the lumenal-exposed
      regions of D1 are indeed long enough to reach these sites. Implanting these
      regions into the stable GFP rendered it sensitive to the presence of Deg1 in
      vitro, demonstrating that the flexible regions of D1 that protrude into the lumen
      can penetrate through the three side-openings of Deg1 and reach its internal
      proteolytic sites. This mode of action, facilitating cooperation between
      proteases on both sides of the thylakoid membranes, should be applicable to the
      degradation of other integral thylakoid membrane proteins as well.

PMID- 29588503
TI  - Cohesively enhanced electrical conductivity and thermal stability of silver
      nanowire networks by nickel ion bridge joining.
AB  - A facile method for producing high-performance nickel enhanced silver nanowire
      (Ag NW) transparent electrodes on a flexible substrate is reported. The modified
      electroplating method called enhanced nickel ion bridge joining of Ag NWs, which
      provides a new route for improving the loose junctions in bare Ag NW networks.
      The sheet resistance of Ag NW electrode drops from over 2000 Omega sq-1 to 9.4
      Omega sq-1 with excellent thermal uniformity after the electroplating process
      within 10 s. Nickel enhanced Ag NW transparent films are applied on flexible
      heaters with good thermal stability (165  degrees C for 2 h) and mechanical
      flexibility (3500 cycles under 2.5 mm bending radius) after mechanical bending
      process. Moreover, the mechanism of nickel growth is also confirmed that the
      nickel electroplating of the Ag NWs obeyed Faraday's Laws.

PMID- 29588502
TI  - Extensive molecular tinkering in the evolution of the membrane attachment mode of
      the Rheb GTPase.
AB  - Rheb is a conserved and widespread Ras-like GTPase involved in cell growth
      regulation mediated by the (m)TORC1 kinase complex and implicated in
      tumourigenesis in humans. Rheb function depends on its association with membranes
      via prenylated C-terminus, a mechanism shared with many other eukaryotic GTPases.
      Strikingly, our analysis of a phylogenetically rich sample of Rheb sequences
      revealed that in multiple lineages this canonical and ancestral membrane
      attachment mode has been variously altered. The modifications include: (1)
      accretion to the N-terminus of two different phosphatidylinositol 3-phosphate
      binding domains, PX in Cryptista (the fusion being the first proposed
      synapomorphy of this clade), and FYVE in Euglenozoa and the related undescribed
      flagellate SRT308; (2) acquisition of lipidic modifications of the N-terminal
      region, namely myristoylation and/or S-palmitoylation in seven different protist
      lineages; (3) acquisition of S-palmitoylation in the hypervariable C-terminal
      region of Rheb in apusomonads, convergently to some other Ras family proteins;
      (4) replacement of the C-terminal prenylation motif with four transmembrane
      segments in a novel Rheb paralog in the SAR clade; (5) loss of an evident C
      terminal membrane attachment mechanism in Tremellomycetes and some Rheb paralogs
      of Euglenozoa. Rheb evolution is thus surprisingly dynamic and presents a
      spectacular example of molecular tinkering.

PMID- 29588504
TI  - Saturation-Recovery Myocardial T1-Mapping during Systole: Accurate and Robust
      Quantification in the Presence of Arrhythmia.
AB  - Myocardial T1-mapping, a cardiac magnetic resonance imaging technique,
      facilitates a quantitative measure of fibrosis which is linked to numerous
      cardiovascular symptoms. To overcome the problems of common techniques, including
      lack of accuracy and robustness against partial-voluming and heart-rate
      variability, we introduce a systolic saturation-recovery T1-mapping method. The
      Saturation-Pulse Prepared Heart-rate independent Inversion-Recovery (SAPPHIRE) T1
      mapping method was modified to enable imaging during systole. Phantom
      measurements were used to evaluate the insensitivity of systolic T1-mapping
      towards heart-rate variability. In-vivo feasibility and accuracy were
      demonstrated in ten healthy volunteers with native and post-contrast T1-mappping
      during systole and diastole. To show benefits in the presence of RR-variability,
      six arrhythmic patients underwent native T1-mapping. Resulting systolic SAPPHIRE
      T1-values showed no dependence on arrhythmia in phantom (CoV < 1%). In-vivo,
      significantly lower T1 (1563 +/- 56 ms, precision: 84.8 ms) and ECV-values (0.20
      +/- 0.03) than during diastole (T1 = 1580 +/- 62 ms, p = 0.0124; precision: 60.2
      ms, p = 0.03; ECV = 0.21 +/- 0.03, p = 0.0098) were measured, with a strong
      correlation of systolic and diastolic T1 (r = 0.89). In patients, mis-triggering
      induced motion caused significant imaging artifacts in diastolic T1-maps, whereas
      systolic T1-maps displayed resilience to arrythmia. In conclusion, the proposed
      method enables saturation-recovery T1-mapping during systole, providing increased
      robustness against partial-voluming compared to diastolic imaging, for the
      benefit of T1-measurements in arrhythmic patients.

PMID- 29588505
TI  - Predation scars may influence host susceptibility to pathogens: evaluating the
      role of corallivores as vectors of coral disease.
AB  - Infectious diseases not regulated by host density, such as vector-borne diseases,
      have the potential to drive population declines and extinctions. Here we test the
      vector potential of the snail Drupella sp. and butterflyfish Chaetodon plebeius
      for two coral diseases, black band (BBD) and brown band (BrB) disease. Drupella
      transmitted BrB to healthy corals in 40% of cases immediately following feeding
      on infected corals, and even in 12% of cases 12 and 24 hours following feeding.
      However, Drupella was unable to transmit BBD in either transmission treatment. In
      a field experiment testing the vector potential of naturally-occurring fish
      assemblages, equivalent numbers of caged and uncaged coral fragments became
      infected with either BrB, BBD or skeletal eroding band, indicating that
      corallivorous fish were unlikely to have caused transmission. In aquaria, C.
      plebeius did not transmit either BBD or BrB, even following extended feeding on
      both infected and healthy nubbins. A literature review confirmed only four known
      coral disease vectors, all invertebrates, corroborating our conclusion that polyp
      feeding fishes are unlikely to be vectors of coral diseases. This potentially
      because polyp-feeding fishes produce shallow lesions, not allowing pathogens to
      invade coral tissues. In contrast, corallivorous invertebrates that create deeper
      feeding scars increase pathogens transmission.

PMID- 29588507
TI  - Human-mediated dispersal of cats in the Neolithic Central Europe.
AB  - Archeological and genetic evidence suggest that all domestic cats derived from
      the Near Eastern wildcat (Felis silvestris lybica) and were first domesticated in
      the Near East around 10,000 years ago. The spread of the domesticated form in
      Europe occurred much later, primarily mediated by Greek and Phoenician traders
      and afterward by Romans who introduced cats to Western and Central Europe around
      2000 years ago. We investigated mtDNA of Holocene Felis remains and provide
      evidence of an unexpectedly early presence of cats bearing the Near Eastern
      wildcat mtDNA haplotypes in Central Europe, being ahead of Roman period by over
      2000 years. The appearance of the Near Eastern wildcats in Central Europe
      coincides with the peak of Neolithic settlement density, moreover most of those
      cats belonged to the same mtDNA lineages as those domesticated in the Near East.
      Thus, although we cannot fully exclude that the Near Eastern wildcats appeared in
      Central Europe as a result of introgression with European wildcat, our findings
      support the hypothesis that the Near Eastern wildcats spread across Europe
      together with the first farmers, perhaps as commensal animals. We also found that
      cats dated to the Neolithic period belonged to different mtDNA lineages than
      those brought to Central Europe in Roman times, this supports the hypothesis that
      the gene pool of contemporary European domestic cats might have been established
      from two different source populations that contributed in different periods.

PMID- 29588506
TI  - Narrow-sense heritability estimation of complex traits using identity-by-descent
      information.
AB  - Heritability is a fundamental parameter in genetics. Traditional estimates based
      on family or twin studies can be biased due to shared environmental or non
      additive genetic variance. Alternatively, those based on genotyped or imputed
      variants typically underestimate narrow-sense heritability contributed by rare or
      otherwise poorly tagged causal variants. Identical-by-descent (IBD) segments of
      the genome share all variants between pairs of chromosomes except new mutations
      that have arisen since the last common ancestor. Therefore, relating phenotypic
      similarity to degree of IBD sharing among classically unrelated individuals is an
      appealing approach to estimating the near full additive genetic variance while
      possibly avoiding biases that can occur when modeling close relatives. We applied
      an IBD-based approach (GREML-IBD) to estimate heritability in unrelated
      individuals using phenotypic simulation with thousands of whole-genome sequences
      across a range of stratification, polygenicity levels, and the minor allele
      frequencies of causal variants (CVs). In simulations, the IBD-based approach
      produced unbiased heritability estimates, even when CVs were extremely rare,
      although precision was low. However, population stratification and non-genetic
      familial environmental effects shared across generations led to strong biases in
      IBD-based heritability. We used data on two traits in ~120,000 people from the UK
      Biobank to demonstrate that, depending on the trait and possible confounding
      environmental effects, GREML-IBD can be applied to very large genetic datasets to
      infer the contribution of very rare variants lost using other methods. However,
      we observed apparent biases in these real data, suggesting that more work may be
      required to understand and mitigate factors that influence IBD-based heritability
      estimates.

PMID- 29588508
TI  - The effects of recent changes in breeding preferences on maintaining traditional
      Dutch chicken genomic diversity.
AB  - Traditional Dutch chicken breeds are marginalised breeds of ornamental and
      cultural-historical importance. In the last decades, miniaturising of existing
      breeds (so called neo-bantam) has become popular and resulted in alternatives to
      original large breeds. However, while backcrossing is increasing the neo-bantams
      homozygosity, genetic exchange between breeders may increase their genetic
      diversity. We use the 60 K SNP array to characterise the genetic diversity,
      demographic history, and level of inbreeding of Dutch heritage breeds, and
      particularly of neo-bantams. Commercial white layers are used to contrast the
      impact of management strategy on genetic diversity and demography. A high
      proportion of alleles was found to be shared between large fowls and neo-bantams,
      suggesting gene flow during neo-bantams development. Population admixture
      analysis supports these findings, in addition to revealing introgression from neo
      bantams of the same breed and of phenotypically similar breeds. The prevalence of
      long runs of homozygosity (ROH) confirms the importance of recent inbreeding. A
      high diversity in management, carried out in small breeding units explains the
      high heterogeneity in diversity and ROH profile displayed by traditional breeds
      compared to commercial lines. Population bottlenecks may explain the long ROHs in
      large fowls, while repetitive backcrossing for phenotype selection may account
      for them in neo-bantams. Our results highlight the importance of using markers to
      inform breeding programmes on potentially harmful homozygosity to prevent loss of
      genetic diversity. We conclude that bantamisation has generated unique and
      identifiable genetic diversity. However, this diversity can only be preserved in
      the near future through structured breeding programmes.

PMID- 29588509
TI  - The road to evolutionary success: insights from the demographic history of an
      Amazonian palm.
AB  - Evolutionary success, as demonstrated by high abundance and a wide geographical
      range, is related to genetic variation and historical demography. Here we assess
      how climatic change during the Quaternary influenced the demography and
      distribution of the Neotropical swamp palm Mauritia flexuosa. Using
      microsatellite loci and coalescent analyses we examined how demographical
      dynamics affected genetic diversity, effective population size and connectivity
      through time and space. Mauritia flexuosa presents significant genetic
      differentiation between the Amazonian and Cerrado biomes and among different
      river basins. Amazonian lineages are ancient compared to lineages from the
      Cerrado, a pattern corroborated using the fossil pollen record, where the species
      was absent from the Cerrado during the cold and dry periods of the last glacial
      cycles, then returned during the wet, interglacial phases. Coalescent simulations
      show that the pattern of observed genetic diversity for M. flexuosa is most
      likely due to a range retraction during the Last Glacial Maximum, leading to
      multiple refugia and resulting in high differentiation between Amazonian and
      Cerrado biomes. Isolation-by-distance and by-environment also shaped the
      distribution and evolutionary success of M. flexuosa. Our study provides new
      insights into the historical factors that affected geographical distribution and
      structure genetic diversity, contributing to long-term evolutionary success.

PMID- 29588510
TI  - Modelling the co-evolution of indirect genetic effects and inherited variability.
AB  - When individuals interact, their phenotypes may be affected not only by their own
      genes but also by genes in their social partners. This phenomenon is known as
      Indirect Genetic Effects (IGEs). In aquaculture species and some plants, however,
      competition not only affects trait levels of individuals, but also inflates
      variability of trait values among individuals. In the field of quantitative
      genetics, the variability of trait values has been studied as a quantitative
      trait in itself, and is often referred to as inherited variability. Such studies,
      however, consider only the genetic effect of the focal individual on trait
      variability and do not make a connection to competition. Although the observed
      phenotypic relationship between competition and variability suggests an
      underlying genetic relationship, the current quantitative genetic models of IGE
      and inherited variability do not allow for such a relationship. The lack of
      quantitative genetic models that connect IGEs to inherited variability limits our
      understanding of the potential of variability to respond to selection, both in
      nature and agriculture. Models of trait levels, for example, show that IGEs may
      considerably change heritable variation in trait values. Currently, we lack the
      tools to investigate whether this result extends to variability of trait values.
      Here we present a model that integrates IGEs and inherited variability. In this
      model, the target phenotype, say growth rate, is a function of the genetic and
      environmental effects of the focal individual and of the difference in trait
      value between the social partner and the focal individual, multiplied by a
      regression coefficient. The regression coefficient is a genetic trait, which is a
      measure of cooperation; a negative value indicates competition, a positive value
      cooperation, and an increasing value due to selection indicates the evolution of
      cooperation. In contrast to the existing quantitative genetic models, our model
      allows for co-evolution of IGEs and variability, as the regression coefficient
      can respond to selection. Our simulations show that the model results in
      increased variability of body weight with increasing competition. When
      competition decreases, i.e., cooperation evolves, variability becomes
      significantly smaller. Hence, our model facilitates quantitative genetic studies
      on the relationship between IGEs and inherited variability. Moreover, our
      findings suggest that we may have been overlooking an entire level of genetic
      variation in variability, the one due to IGEs.

PMID- 29588511
TI  - Structure and Distribution of an Unrecognized Interstitium in Human Tissues.
AB  - Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of
      human tissues at a depth of 60-70 MUm during endoscopy. pCLE of the extrahepatic
      bile duct after fluorescein injection demonstrated a reticular pattern within
      fluorescein-filled sinuses that had no known anatomical correlate. Freezing
      biopsy tissue before fixation preserved the anatomy of this structure,
      demonstrating that it is part of the submucosa and a previously unappreciated
      fluid-filled interstitial space, draining to lymph nodes and supported by a
      complex network of thick collagen bundles. These bundles are intermittently lined
      on one side by fibroblast-like cells that stain with endothelial markers and
      vimentin, although there is a highly unusual and extensive unlined interface
      between the matrix proteins of the bundles and the surrounding fluid. We observed
      similar structures in numerous tissues that are subject to intermittent or
      rhythmic compression, including the submucosae of the entire gastrointestinal
      tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft
      tissues, and fascia. These anatomic structures may be important in cancer
      metastasis, edema, fibrosis, and mechanical functioning of many or all tissues
      and organs. In sum, we describe the anatomy and histology of a previously
      unrecognized, though widespread, macroscopic, fluid-filled space within and
      between tissues, a novel expansion and specification of the concept of the human
      interstitium.

PMID- 29588512
TI  - Multivariable clinical-genetic risk model for predicting venous thromboembolic
      events in patients with cancer.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death among
      patients with cancer. Outpatients with cancer should be periodically assessed for
      VTE risk, for which the Khorana score is commonly recommended. However, it has
      been questioned whether this tool is sufficiently accurate at identifying
      patients who should receive thromboprophylaxis. The present work proposes a new
      index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer,
      that examines patients' clinical and genetic risk factors for thrombosis.
      METHODS: We included 391 outpatients with a recent diagnosis of cancer and
      candidates for systemic outpatient chemotherapy. All were treated according to
      standard guidelines. The study population was monitored for 6 months, and VTEs
      were recorded. The Khorana and the TiC-Onco scores were calculated for each
      patient and their VTE predictive accuracy VTEs was compared. RESULTS: We recorded
      71 VTEs. The TiC-Onco risk score was significantly better at predicting VTE than
      the Khorana score (AUC 0.73 vs. 0.58, sensitivity 49 vs. 22%, specificity 81 vs.
      82%, PPV 37 vs. 22%, and NPV 88 vs. 82%). CONCLUSIONS: TiC-Onco risk score
      performed significantly better than Khorana score at identifying cancer patients
      at high risk of VTE who would benefit from personalised thromboprophylaxis.

PMID- 29588515
TI  - Antivirals: Topical therapy for ocular herpes.

PMID- 29588514
TI  - Influence of optic disc-fovea distance on macular thickness measurements with OCT
      in healthy myopic eyes.
AB  - Assessment of macular thickness is important in the evaluation of various eye
      diseases. This study aimed to determine the influence of the optic disc-fovea
      distance (DFD) on macular thickness in myopic eyes. We determined the DFD and the
      macular thickness in 138 eyes from 138 healthy myopic subjects using the Cirrus
      HD-OCT. Correlation analysis and multiple linear regression were performed to
      determine the influence of DFD, axial length, disc area, and beta-PPA on macular
      thickness. To further remove the confounding effect of ocular magnification on
      the DFD and OCT scan area, a subgroup analysis was performed in eyes with a
      limited axial length range (24-25 mm). DFD was significantly correlated with both
      regional (central, inner, and outer ETDRS subfields) and overall average macular
      thickness at a Bonferroni corrected P value of 0.004 (r ranging from -0.27 to 
      0.47), except for the temporal outer (r = -0.15, P = 0.089) and inferior outer (r
      = -0.22, P = 0.011) macular thickness. In the multivariable analysis, DFD was
      significantly associated with the average inner and outer macular thickness, the
      central subfield thickness, and the overall macular thickness (all P < 0.001),
      independent of ocular magnification and other covariates. Our findings indicate
      that eyes with a greater DFD have a lower macular thickness.

PMID- 29588516
TI  - Market watch: Top drugs and companies by sales in 2017.

PMID- 29588513
TI  - Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive
      breast cancer, especially ER+ luminal subtypes.
AB  - BACKGROUND: Mediator complex (MED) proteins have a key role in transcriptional
      regulation, some interacting with the oestrogen receptor (ER). Interrogation of
      the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion
      (LVI). Thus MED7 expression was assessed in large breast cancer (BC) cohorts to
      determine clinicopathological significance. METHODS: MED7 gene expression was
      investigated in the METABRIC cohort (n = 1980) and externally validated using bc
      GenExMiner v4.0. Immunohistochemical expression was assessed in the Nottingham
      primary BC series (n = 1280). Associations with clinicopathological variables and
      patient outcome were evaluated. RESULTS: High MED7 mRNA and protein expression
      was associated with good prognostic factors: low grade, smaller tumour size, good
      NPI, positive hormone receptor status (p < 0.001), and negative LVI (p = 0.04)
      status. Higher MED7 protein expression was associated with improved BC-specific
      survival within the whole cohort and ER+/luminal subgroup. Pooled MED7 gene
      expression data in the external validation cohort confirmed association with
      better survival, corroborating with the protein expression. On multivariate
      analysis, MED7 protein was independently predictive of longer BC-specific
      survival in the whole cohort and Luminal A subtype (p < 0.001). CONCLUSIONS: MED7
      is an important prognostic marker in BC, particularly in ER+luminal subtypes,
      associated with improved survival and warrants future functional analysis.

PMID- 29588518
TI  - George Yancopoulos.

PMID- 29588517
TI  - Drug delivery: DNA nanorobots - seek and destroy.

PMID- 29588519
TI  - Infectious disease: Virus-based tuberculosis vaccine.

PMID- 29588520
TI  - Immunotherapy: iPSC-based cancer vaccine.

PMID- 29588521
TI  - Neurodevelopmental disorders: CRISPR to the rescue.

PMID- 29588522
TI  - Sepsis: Gut bacteria induce protective IgA.

PMID- 29588523
TI  - Market watch: Upcoming market catalysts in Q2 2018.

PMID- 29588524
TI  - SUMO suppresses and MYC amplifies transcription globally by regulating CDK9
      sumoylation.
AB  - Regulation of transcription is fundamental to the control of cellular gene
      expression and function. Although recent studies have revealed a role for the
      oncoprotein MYC in amplifying global transcription, little is known as to how the
      global transcription is suppressed. Here we report that SUMO and MYC mediate
      opposite effects upon global transcription by controlling the level of CDK9
      sumoylation. On one hand, SUMO suppresses global transcription via sumoylation of
      CDK9, the catalytic subunit of P-TEFb kinase essential for productive
      transcriptional elongation. On the other hand, MYC amplifies global transcription
      by antagonizing CDK9 sumoylation. Sumoylation of CDK9 blocks its interaction with
      Cyclin T1 and thus the formation of active P-TEFb complex. Transcription
      profiling analyses reveal that SUMO represses global transcription, particularly
      of moderately to highly expressed genes and by generating a sumoylation-resistant
      CDK9 mutant, we confirm that sumoylation of CDK9 inhibits global transcription.
      Together, our data reveal that SUMO and MYC oppositely control global gene
      expression by regulating the dynamic sumoylation and desumoylation of CDK9.

PMID- 29588527
TI  - Intestinal tract: A breach in the intestinal barrier during hyperglycaemia.

PMID- 29588526
TI  - Multistep transition of diamond to warm dense matter state revealed by
      femtosecond X-ray diffraction.
AB  - Diamond bulk irradiated with a free-electron laser pulse of 6100 eV photon
      energy, 5 fs duration, at the ~19-25 eV/atom absorbed doses, is studied
      theoretically on its way to warm dense matter state. Simulations with our hybrid
      code XTANT show disordering on sub-100 fs timescale, with the diffraction peak
      (220) vanishing faster than the peak (111). The warm dense matter formation
      proceeds as a nonthermal damage of diamond with the band gap collapse triggering
      atomic disordering. Short-living graphite-like state is identified during a few
      femtoseconds between the disappearance of (220) peak and the disappearance of
      (111) peak. The results obtained are compared with the data from the recent
      experiment at SACLA, showing qualitative agreement. Challenges remaining for the
      accurate modeling of the transition of solids to warm dense matter state and
      proposals for supplementary measurements are discussed in detail.

PMID- 29588525
TI  - Succinate-acetate permease from Citrobacter koseri is an anion channel that
      unidirectionally translocates acetate.
AB  - Acetate is an important metabolite in metabolism and cell signaling. Succinate
      Acetate Permease (SatP) superfamily proteins are known to be responsible for
      acetate transport across membranes, but the nature of this transport remains
      unknown. Here, we show that the SatP homolog from Citrobacter koseri (SatP_Ck) is
      an anion channel that can unidirectionally translocate acetate at rates of the
      order of ~107 ions/s. Crystal structures of SatP_Ck in complex with multiple
      acetates at 1.8 A reveal that the acetate pathway consists of four acetate
      binding sites aligned in a single file that are interrupted by three hydrophobic
      constrictions. The bound acetates at the four sites are each orientated
      differently. The acetate at the cytoplasmic vestibule is partially dehydrated,
      whereas those in the main pore body are fully dehydrated. Aromatic residues
      within the substrate pathway may coordinate translocation of acetates via anion
      pi interactions. SatP_Ck reveals a new type of selective anion channel and
      provides a structural and functional template for understanding organic anion
      transport.

PMID- 29588528
TI  - Impact of delay in early swallow screening on pneumonia, length of stay in
      hospital, disability and mortality in acute stroke patients.
AB  - BACKGROUND/OBJECTIVES: Early swallow screening, within 4 h of admission, is
      required for all acute stroke patients to commence nutritional support, as
      recommended. We evaluated the impact of delay in early swallow screening on
      outcomes in patients admitted with acute stroke. SUBJECTS/METHODS: Prospective
      cohort study of 1656 men (mean +/- SD age = 73.1y +/- 13.2) and 1653 women (79.3y
      +/- 13.0) admitted with stroke to hyperacute stroke units (HASUs) in Surrey.
      Logistic regression was used to assess the risk (adjusted for age, stroke
      severity and co-morbidities) of delay in swallow screening on pneumonia, length
      of stay (LOS) > 3 weeks in HASU or hospital, moderately severe to severe
      disability on discharge (modified Rankin scale score = 4-5) and mortality during
      admission. RESULTS: Compared with those who received swallow screening within 4 h
      of admission, a delay between 4 and 72 h was associated with greater risks of
      pneumonia: OR = 1.4 (95%CI:1.1-1.9, P = 0.022), moderately severe to severe
      disability on discharge: OR = 1.4 (1.1-1.7, P = 0.007) and a delay beyond 72 h
      was associated with even greater risks of pneumonia: OR = 2.3 (1.4-3.6, P <
      0.001), prolonged LOS in HASU: OR = 1.7 (1.0-3.0, P = 0.047, median LOS = 6.2 vs.
      14.7 days) and hospital: OR = 2.1-fold (1.3-3.4, P = 0.007, median LOS = 6.8 vs.
      14.9 days), moderately severe to severe disability on discharge: OR = 2.5 (1.7
      3.7, P < 0.001) and mortality: OR = 3.8 (2.5-5.6, P < 0.001). These risks
      persisted after excluding 103 patients who died within 72 h. CONCLUSIONS: Delay
      in early screening for swallow capacity in acute stroke patients is detrimental
      to outcomes, possibly due to delaying nutritional provision or through
      inappropriate feeding leading to aspiration. Routine early screening needs
      greater attention in HASUs.

PMID- 29588529
TI  - Malnutrition risk is associated with hypoglycemia among general population
      admitted to internal medicine units. Results from the MENU study.
AB  - BACKGROUND/OBJECTIVES: To examine the association between increased malnutrition
      risk upon admission, and the incidence of hypoglycemia among adult patients
      admitted to internal medicine units in Israel. SUBJECTS/METHODS: This was a cross
      sectional study, and included were all adult patients admitted to internal
      medicine units, regardless of reason for admission. The NRS2002 was used to for
      nutritional screening. All glucose measurements were obtained using an
      institutional blood glucose-monitoring system, which consisted of a point of
      care, automated glucometer, and an interactive database. Patients were
      categorized as hypoglycemic if they had at least one documented hypoglycemia (=
      <70 mg/dL) event during the hospitalization period. Blood chemistry measured at
      admission was also recorded. RESULTS: Included were 876 patients (mean age 70.0
      +/- 17.3, 50.6% were males). Rate of positive malnutrition screen was 39.7% of
      the population. A total of 5.4% of the study population had at least one
      hypoglycemic event during hospitalization. Rate of diabetes mellitus did not
      differ between patients with or without hypoglycemia. A greater proportion of
      patients with hypoglycemia were at increased malnutrition risk compared to
      patients without documented hypoglycemic events (56.8% vs. 38.9%, p = 0.018).
      Patients who had hypoglycemia had higher NRS2002 scores for pre-hospitalization
      unintentional weight loss and reduced food consumed. In logistic regression
      analysis, increased malnutrition risk was associated with hypoglycemia occurrence
      (OR 1.982, 95% confidence interval 1.056-3.718, p = 0.033). Age, sex, and
      diabetes mellitus status did not affect the rate of hypoglycemia. CONCLUSIONS:
      Our data suggest increased malnutrition risk as measured by the NRS2002 almost
      doubled the risk for hypoglycemia during the hospitalization.

PMID- 29588530
TI  - Knowledge and behaviors regarding salt intake in Mozambique.
AB  - BACKGROUND/OBJECTIVES: Health education and regulatory measures may contribute to
      lower population salt intake. Therefore, we aimed to describe knowledge and
      behaviors related to salt intake in Mozambique. SUBJECTS/METHODS: A cross
      sectional evaluation of a representative sample of the population aged 15-64
      years (n = 3116) was conducted in 2014/2015, following the Stepwise Approach to
      Chronic Disease Risk Factor Surveillance, including a 12-question module for
      evaluation of dietary salt. RESULTS: Three dimensions were identified in the
      questionnaire, named "self-reported salt intake", "knowledge of health effects of
      salt intake", and "behaviors for control of salt intake". A total of 7.4% of the
      participants perceived that they consumed too much/far too much salt and 25.9%
      reported adding salt/salty seasoning often/always to prepared foods. The
      proportion considering that it was not important to decrease the salt contents of
      their diet was 8%, and 16.9% were not aware that high salt intake could be
      deleterious for health. Prevalences of lack of behaviors for reducing salt intake
      ranged from 74.9% for not limiting consumption of processed foods, to 95% for not
      buying low salt alternatives. There were few differences according to socio
      demographic variables, but awareness of hypertension was, in general, associated
      with better knowledge and less frequent behaviors likely to contribute to a high
      salt intake. CONCLUSIONS: Most Mozambicans were aware that high salt intake can
      cause health problems, but the self-reported salt intake and behaviors for its
      control show an ample margin for improvement. This study provides evidence to
      guide population level salt-reducing policies.

PMID- 29588531
TI  - Review of case reports on hyperkalemia induced by dietary intake: not restricted
      to chronic kidney disease patients.
AB  - Hyperkalemia is a metabolic disturbance of the potassium balance that can cause
      potentially fatal cardiac arrhythmias. Kidney dysfunction and renin-angiotensin
      aldosterone system inhibiting drugs are notorious for their tendency to induce
      hyperkalemia by decreasing the excretion of potassium. The role of dietary
      potassium intake in inducing hyperkalemia is less clear. We review and analyze
      the common presentation, laboratory, and electrocardiogram (ECG) findings and
      therapeutic options associated with dietary-induced hyperkalemia, and find
      evidence for hyperkalemia development in non-renal impaired patients. Thirty-five
      case reports including 44 incidences of oral intake-induced hyperkalemia were
      assessed, 17 patients did not suffer from kidney dysfunction. Mean age was 49 +/-
      20 years. Mean potassium concentration was 8.2 +/- 1.4 mEq/l, most frequently
      caused by abundant intake of fruit and vegetables (n = 17) or salt substitutes (n
      = 12). In patients with normal kidney function, intake of salt substitutes or
      supplements was the main cause of hyperkalemia. Main symptoms encompassed muscle
      weakness (29.5%), vomiting (20.4%), and dyspnea (15.9%). When ECGs were performed
      (n = 30), abnormalities were present in 86.7% of cases. Treatment involved
      administration of insulin (n = 22), sodium/calcium polystyrene sulfonate (n =
      14), and/or calcium gluconate (n = 14). Forty patients fully recovered. Three,
      non-renal impaired, patients passed away. These results offer insight into the
      clinical aspects of dietary-induced hyperkalemia and suggest that the common
      assumption that dietary-induced hyperkalemia is a condition of renal impaired
      patients might be incorrect.

PMID- 29588532
TI  - Molecular changes preceding endometrial and ovarian cancer: a study of
      consecutive endometrial specimens from Lynch syndrome surveillance.
AB  - Molecular alterations preceding endometrial and ovarian cancer and the sequence
      of events are unknown. Consecutive specimens from lifelong surveillance for Lynch
      syndrome provides a natural setting to address such questions. To molecularly
      define the multistep gynecological tumorigenesis, DNA mismatch repair gene
      mutation carriers with endometrial or ovarian carcinoma or endometrial
      hyperplasia were identified from a nation-wide registry and endometrial biopsy
      specimens taken from these individuals during 20 years of screening were
      collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome
      individuals and 197 histology-matched (non-serous) samples from sporadic cases
      were available for this investigation. The specimens were profiled for markers
      linked to endometrial and ovarian tumorigenesis, including ARID1A protein
      expression, mismatch repair status, and tumor suppressor gene promoter
      methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas,
      ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%,
      compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared
      in complex hyperplasia and deficient mismatch repair and tumor suppressor gene
      promoter methylation in histologically normal endometrium. Despite quantitative
      differences between Lynch syndrome and sporadic cases, ARID1A expression,
      mismatch repair, and tumor suppressor gene promoter methylation divided
      endometrial samples from both patient groups into three categories of increasing
      abnormality, comprising normal endometrium and simple hyperplasia (I), complex
      hyperplasia with or without atypia (II), and endometrial cancer (III). Complex
      hyperplasias without vs. with atypia were molecularly indistinguishable. In
      conclusion, surveillance specimens from Lynch syndrome identify mismatch repair
      deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early
      changes in tumor development. Our findings are clinically relevant for the
      classification of endometrial hyperplasias and have potential implications in
      cancer prevention in Lynch syndrome and beyond.

PMID- 29588533
TI  - The quest for quasispecies.
AB  - This month marks 40 years since the publication of 'Nucleotide sequence
      heterogeneity of an RNA phage population' in Cell. We spoke with Esteban Domingo,
      leading author of this landmark study carried out during his postdoctoral work in
      Charles Weissman's lab, which proposed RNA viral populations to be quasispecies.

PMID- 29588534
TI  - Discovering antibiotics from the global microbiome.

PMID- 29588535
TI  - The TRiCky business of reovirus assembly.

PMID- 29588536
TI  - United we stand and divided we fall.

PMID- 29588537
TI  - Viral programming of progenitor cell commitment.

PMID- 29588540
TI  - Viruses are models for embracing diversity.

PMID- 29588538
TI  - Campylobacter jejuni transcriptional and genetic adaptation during human
      infection.
AB  - Campylobacter jejuni infections are a leading cause of bacterial food-borne
      diarrhoeal illness worldwide, and Campylobacter infections in children are
      associated with stunted growth and therefore long-term deficits into adulthood.
      Despite this global impact on health and human capital, how zoonotic C. jejuni
      responds to the human host remains unclear. Unlike other intestinal pathogens, C.
      jejuni does not harbour pathogen-defining toxins that explicitly contribute to
      disease in humans. This makes understanding Campylobacter pathogenesis
      challenging and supports a broad examination of bacterial factors that contribute
      to C. jejuni infection. Here, we use a controlled human infection model to
      characterize C. jejuni transcriptional and genetic adaptations in vivo, along
      with a non-human primate infection model to validate our approach. We found that
      variation in 11 genes is associated with either acute or persistent human
      infections and includes products involved in host cell invasion, bile sensing and
      flagella modification, plus additional potential therapeutic targets. In
      particular, a functional version of the cell invasion protein A (cipA) gene
      product is strongly associated with persistently infecting bacteria and we
      identified its biochemical role in flagella modification. These data characterize
      the adaptive C. jejuni response to primate infections and suggest therapy design
      should consider the intrinsic differences between acute and persistently
      infecting bacteria. In addition, RNA sequencing revealed conserved responses
      during natural host commensalism and human infections. Thirty-nine genes were
      differentially regulated in vivo across hosts, lifestyles and C. jejuni strains.
      This conserved in vivo response highlights important C. jejuni survival
      mechanisms such as iron acquisition and evasion of the host mucosal immune
      response. These advances highlight pathogen adaptability across host species and
      demonstrate the utility of multidisciplinary collaborations in future clinical
      trials to study pathogens in vivo.

PMID- 29588539
TI  - Metabolic coupling on roots.

PMID- 29588541
TI  - Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for
      disease control.
AB  - G-protein signalling pathways are involved in sensing the environment, enabling
      fungi to coordinate cell function, metabolism and development with their
      surroundings, thereby promoting their survival, propagation and virulence. G
      protein-coupled receptors (GPCRs) are the largest class of cell surface receptors
      in fungi. Despite the apparent importance of GPCR signalling to fungal biology
      and virulence, relatively few GPCR-G-protein interactions, and even fewer
      receptor-binding ligands, have been identified. Approximately 40% of current
      pharmaceuticals target human GPCRs, due to their cell surface location and
      central role in cell signalling. Fungal GPCRs do not belong to any of the
      mammalian receptor classes, making them druggable targets for antifungal
      development. This Review Article evaluates developments in our understanding of
      fungal GPCR-mediated signalling, while substantiating the rationale for
      considering these receptors as potential antifungal targets. The need for
      insights into the structure-function relationship of receptor-ligand interactions
      is highlighted, which could facilitate the development of receptor-interfering
      compounds that could be used in disease control.

PMID- 29588542
TI  - Human cytomegalovirus reprogrammes haematopoietic progenitor cells into
      immunosuppressive monocytes to achieve latency.
AB  - The precise cell type hosting latent human cytomegalovirus (HCMV) remains
      elusive. Here, we report that HCMV reprogrammes human haematopoietic progenitor
      cells (HPCs) into a unique monocyte subset to achieve latency. Unlike
      conventional monocytes, this monocyte subset possesses higher levels of B7-H4, IL
      10 and inducible nitric oxide synthase (iNOS), a longer lifespan and strong
      immunosuppressive capacity. Cell sorting of peripheral blood from latently
      infected human donors confirms that only this monocyte subset, representing less
      than 0.1% of peripheral mononuclear cells, is HCMV genome-positive but immediate
      early-negative. Mechanistic studies demonstrate that HCMV promotes the
      differentiation of HPCs into this monocyte subset by activating cellular signal
      transducer and activator of transcription 3 (STAT3). In turn, this monocyte
      subset generates a high level of nitric oxide (NO) to silence HCMV immediate
      early transcription and promote viral latency. By contrast, the US28-knockout
      HCMV mutant, which is incapable of activating STAT3, fails to reprogramme the
      HPCs and achieve latency. Our findings reveal that via activating the STAT3-iNOS
      NO axis, HCMV differentiates human HPCs into a longevous, immunosuppressive
      monocyte subset for viral latency.

PMID- 29588543
TI  - Urinary CE-MS peptide marker pattern for detection of solid tumors.
AB  - Urinary profiling datasets, previously acquired by capillary electrophoresis
      coupled to mass-spectrometry were investigated to identify a general urinary
      marker pattern for detection of solid tumors by targeting common systemic events
      associated with tumor-related inflammation. A total of 2,055 urinary profiles
      were analyzed, derived from a) a cancer group of patients (n = 969) with bladder,
      prostate, and pancreatic cancers, renal cell carcinoma, and cholangiocarcinoma
      and b) a control group of patients with benign diseases (n = 556), inflammatory
      diseases (n = 199) and healthy individuals (n = 331). Statistical analysis was
      conducted in a discovery set of 676 cancer cases and 744 controls. 193 peptides
      differing at statistically significant levels between cases and controls were
      selected and combined to a multi-dimensional marker pattern using support vector
      machine algorithms. Independent validation in a set of 635 patients (293 cancer
      cases and 342 controls) showed an AUC of 0.82. Inclusion of age as independent
      variable, significantly increased the AUC value to 0.85. Among the identified
      peptides were mucins, fibrinogen and collagen fragments. Further studies are
      planned to assess the pattern value to monitor patients for tumor recurrence. In
      this proof-of-concept study, a general tumor marker pattern was developed to
      detect cancer based on shared biomarkers, likely indicative of cancer-related
      features.

PMID- 29588544
TI  - Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies
      overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation.

PMID- 29588545
TI  - Validation of a biological score to predict response in chronic lymphocytic
      leukemia patients treated front-line with bendamustine and rituximab.

PMID- 29588547
TI  - Ongoing clonal evolution in chronic myelomonocytic leukemia on hypomethylating
      agents: a computational perspective.

PMID- 29588548
TI  - A Helicopter Emergency Medical Service for Northern Ireland.

PMID- 29588546
TI  - The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3
      skewing of anaplastic large cell lymphoma.
AB  - Transcription factor AP-1 is constitutively activated and IRF4 drives growth and
      survival in ALK+ and ALK- anaplastic large cell lymphoma (ALCL). Here we
      demonstrate high-level BATF and BATF3 expression in ALCL. Both BATFs bind
      classical AP-1 motifs and interact with in ALCL deregulated AP-1 factors.
      Together with IRF4, they co-occupy AP-1-IRF composite elements, differentiating
      ALCL from non-ALCL. Gene-specific inactivation of BATFs, or global AP-1
      inhibition results in ALCL growth retardation and/or cell death in vitro and in
      vivo. Furthermore, the AP-1-BATF module establishes TH17/group 3 innate lymphoid
      cells (ILC3)-associated gene expression in ALCL cells, including marker genes
      such as AHR, IL17F, IL22, IL26, IL23R and RORgammat. Elevated IL-17A and IL-17F
      levels were detected in a subset of children and adolescents with ALK+ ALCL.
      Furthermore, a comprehensive analysis of primary lymphoma data confirms TH17-,
      and in particular ILC3-skewing in ALCL compared with PTCL. Finally,
      pharmacological inhibition of RORC as single treatment leads to cell death in
      ALCL cell lines and, in combination with the ALK inhibitor crizotinib, enforces
      death induction in ALK+ ALCL. Our data highlight the crucial role of AP-1/BATFs
      in ALCL and lead to the concept that some ALCL might originate from ILC3.

PMID- 29588549
TI  - 'When Right could be so Wrong'. Laterality Errors in Healthcare.

PMID- 29588550
TI  - Far away from the NHS - Hernia Surgery in Nigeria and Kenya.

PMID- 29588551
TI  - Hip Hemi-Arthroplasty vs Total Hip Replacement for Displaced Intra-Capsular Hip
      Fractures: Retrospective Age and Sex Matched Cohort Study.
AB  - Introduction: The Royal Victoria Hospital in Belfast is the largest volume
      hospital in the UK Hip Fracture Database. Management of displaced intra-capsular
      hip fractures is evolving in light of NICE2 and BOA guidelines3, with more
      patients receiving total hip replacement (THR) over hemi-arthroplasty. With
      current rationing within the NHS, it is vital that principles of the 'Getting It
      Right First time' (GIRFT) report4 are implemented and the correct treatment
      choice made. Our aim was to assess Barthel scores5, complication rate, blood
      transfusion rate and post op functional ability in two age and sex matched
      cohorts to see if our patient selection was appropriate. Methods: Between January
      and December 2013, 2 age and sex matched cohorts each containing 46 hip fracture
      patients were retrospectively identified. The first group underwent Hip Hemi
      Arthroplasty (HHA) and the second group underwent THR. We looked at complication
      rate, blood transfusion rate, pre- and post-operative locomotor ability as well
      as Barthel score5. Results: Average age in the HHA group was 69.7 with an average
      ASA grade of 2.61, compared to 71.2 and 2.43 respectively in the THR group.
      Complication rate in the HHA group was 45.6% with 2/3 due to chest sepsis or
      urosepsis. The THR group had a complication rate of 8.7% with 3/4 due to venous
      thrombembolism, reflecting the better pre-morbid physiological function in this
      cohort. Blood transfusion rates were similar in both groups. Barthel scores5
      showed average reductions of 2.67 in the HHA group and 0.30 in the THR group.
      Conclusions: The application of the NICE guidelines2 for arthroplasty choice in
      hip fracture management has led to judicious patient selection for THR. The THR
      group had a significantly lower complication rate (p<0.05) and better Barthel
      scores5 (p<0.05) compared to the HHA group. In addition, having a higher ASA
      score (III or IV) or lower Barthel score5 pre-operatively were independent
      predictors of complication occurrence.

PMID- 29588552
TI  - ESCAPE to Reality, Post-Trial Outcomes in an ESCAPE Centre: A Retrospective Case
      Control Study.
AB  - Introduction: The Royal Victoria Hospital, Belfast provides the regional
      neuroendovascular service for Northern Ireland and was an enrolling centre for
      the ESCAPE endovascular stroke trial. Our aim was to assess outcomes for patients
      presenting with acute stroke following discontinuation of trial enrolment at our
      centre. Methods: We collected data on all patients presenting with acute stoke
      between Nov-1st-2014 and Oct-31st-2015 who received endovascular treatment or
      received IV thrombolysis (IV-tPA) alone. ESCAPE eligibility of each patient was
      assessed. Primary outcome was modified Rankin Score (mRS) at 3 months. Results:
      129 patients presented with acute stoke symptoms during the time period; 56/129
      (43.4%) patients in the intervention group and 73/129 (56.5%) patients in the
      control group. In the interventional group, 42/56 (75%) were considered ESCAPE
      eligible and 14/56 (25%) were considered ESCAPE ineligible. 30/42 (71.4%) ESCAPE
      eligible patients had a positive functional outcome at 3 months compared to 9/14
      (64.2%) ESCAPE ineligible patients. In the control group, 37 (50.7%) had
      identifiable thrombotic occlusion and 13/37 (35.1%) were considered eligible for
      intervention. 4/13 (30.8%) achieved functional independence (mRS<3) at 3
      months.There was a statistically significant difference in functional
      independence in those who underwent endovascular therapy compared to the control
      group (p= 0.04). Conclusion: ESCAPE eligible patients in our centre had
      favourable outcome rates superior to the published trial data. ESCAPE ineligible
      patients tended to do slightly less well, but still better than the favourable
      outcome rates achieved with IVtPA alone. There is potentially a wide discordance
      between the threshold for futility and trial eligibility criteria when
      considering endovascular treatment for acute ischaemic stroke.

PMID- 29588553
TI  - Age adjusted D-dimer in the Belfast Health and Social Care Trust: A retrospective
      study.
AB  - D-dimers combined with clinical pre-test probability (PTP) scores are used to
      determine the likelihood of a venous thromboembolic event (VTE). It is recognised
      that with advancing age, d-dimer values increase, leading to a cohort of patients
      with a d-dimer above the standard cut-off of 500MUg/L. A recent systemic review,
      examined the accuracy of an age-adjusted D-dimer in those aged > 50 years with a
      low clinical risk of a VTE. This showed an increase in specificity without loss
      of sensitivity. Our study, aimed to examine a population of patients, who between
      2011 and 2014 underwent ultrasound Doppler studies of lower limbs. By applying a
      corresponding age-adjusted D-dimer, we determined the sensitivity and specificity
      and compared this to use of conventional D-dimer.

PMID- 29588554
TI  - Microvascular Decompression for Trigeminal Neuralgia: A regional unit's
      experience.

PMID- 29588556
TI  - Sinoatrial Node Disease in Adults with Down's Syndrome.

PMID- 29588555
TI  - Insulin Autoimmune Syndrome: a rare case of hypoglycaemia resolving with
      immunosuppression.
AB  - We report a case of a 58-year-old male presenting with confusion and
      hypoglycaemia. There had been no prior exposure to oral hypoglycaemic agents or
      insulin. He was found to have inappropriate endogenous hyperinsulinaemia.
      Insulinoma was excluded by detailed endocrine assessment. Insulin antibodies were
      positive in keeping with a diagnosis of insulin autoimmune syndrome (IAS). He was
      treated with prednisolone 5mg once daily and nutritional supplements leading to
      resolution of acute confusion and hypoglycaemic episodes. The patient also had
      severe psoriasis and following discharge was treated with a variety of
      immunosuppressant therapies. This was associated with disappearance of insulin
      antibodies after twelve months of follow up. While it is possible that there was
      spontaneous resolution of insulin antibodies, we speculate that his prednisolone
      and immunosuppressant therapy may have suppressed insulin antibody production.
      There are several well recognised associations with IAS and autoimmune
      conditions, including Grave's disease, systemic lupus erythematous and rheumatoid
      arthritis. To our knowledge this is the first reported case of insulin autoimmune
      syndrome, resolving with immunosuppressant treatment of psoriasis.

PMID- 29588557
TI  - FDR and American Military Deployment: "My" Armed Forces and their Health.

PMID- 29588558
TI  - E-learning for medical education: reflections of learners on patients.
AB  - Introduction: There is a growing research interest in how healthcare
      professionals learn online. This paper reports an analysis of reflections that
      relate to patients from users of an e-learning resource, BMJ Learning. Methods:
      Healthcare professionals who use BMJ Learning are encouraged to reflect on their
      learning. Over one year, all of the learners' reflections that related to
      patients were captured by the programme's software and were analysed using
      thematic analysis. Results: A number of key themes emerged from this analysis:
      many learners reflected on patients in the context of their disease; many
      learners reflected on how they had put their learning into action or planned to
      put their learning into action for the benefit of patients; many learners
      reflected on how they would pass on what they had learned to patients; learners
      greatly appreciated patients contributing to the learning. Discussion: Learners
      predominantly reflect about patients in the context of their disease. The
      reflections demonstrate that learners are keen to put their learning into action
      for the benefit of their patients. Learners' reflections show a keen interest in
      the patient-centredness of the learning resources.

PMID- 29588559
TI  - CHRONIC RING EROSION OF A FINGER.

PMID- 29588560
TI  - OUTCOME OF SUPRAVENTRICULAR TACHYCARDIA IN INFANCY AFTER 4-YEAR FOLLOW-UP.

PMID- 29588561
TI  - CAUGHT RED HANDED- CONGO STAINING IN THE OROPHARYNX.

PMID- 29588562
TI  - FOUNDATION DOCTORS' AUDITS: EFFECTIVE OR NOT?

PMID- 29588563
TI  - CENTRIFUGATION IN GP PRACTICES - CAN IT IMPROVE DIAGNOSTIC EFFICIENCY?

PMID- 29588566
TI  - RADIOFREQUENCY ABLATION AND ENDOSCOPIC MUCOSAL IN TREATMENT OF EARLY NEOPLASTIC
      BARRETT'S OESOPHAGUS.

PMID- 29588565
TI  - ORAL DRUG THERAPY - IMPROVING SURVIVAL IN MALIGNANT MELANOMA.

PMID- 29588567
TI  - DUAL ENERGY SINGLE SOURCE CT CORONARY PERFUSION ANGIOGRAPHY - A HELPFUL
      FUNCTIONAL ADJUNCT TO ANATOMICAL INFORMATION.

PMID- 29588568
TI  - So you want to be a Summer Student?

PMID- 29588569
TI  - In vivo assessment of changes in corneal hysteresis and lamina cribrosa position
      during acute intraocular pressure elevation in eyes with markedly asymmetrical
      glaucoma.
AB  - Purpose: To investigate the biomechanical response of the cornea, lamina cribrosa
      (LC), and prelaminar tissue (PT) to an acute intraocular pressure (IOP) increase
      in patients with markedly asymmetrical glaucoma and in healthy controls. Patients
      and methods: A total of 24 eyes of 12 patients with markedly asymmetrical primary
      open-angle glaucoma (POAG) and 12 eyes of 12 healthy patients were examined with
      spectral-domain optical coherence tomography (SD-OCT) and ocular response
      analyzer (ORA) at baseline and during acute IOP elevation by means of an
      ophthalmodynamometer. The displacement of the LC and PT and the change in corneal
      hysteresis (CH) and corneal resistance factor (CRF) were evaluated. Results:
      Following a mean IOP increase of 12.3+/-2.4 mmHg, eyes with severe glaucoma
      demonstrated an overall mean anterior displacement of the LC (-6.58+/-26.09 um)
      as opposed to the posterior laminar displacement in eyes with mild glaucoma
      (29.08+/-19.28 um) and in healthy eyes (30.3+/-10.9; p<=0.001 and p=0.001,
      respectively). The PT displaced posteriorly during IOP elevation in all eyes. The
      CH decreased in eyes with severe glaucoma during IOP elevation (from 9.30+/-3.65
      to 6.92+/-3.04 mmHg; p=0.012), whereas the CRF increased markedly in eyes with
      mild glaucoma (from 8.61+/-2.30 to 12.38+/-3.64; p=0.002) and in eyes with severe
      glaucoma (from 9.02+/-1.48 to 15.20+/-2.06; p=0.002). The increase in CRF
      correlated with the anterior displacement of the LC in eyes with severe glaucoma.
      Conclusion: Eyes with severe glaucoma exhibited a mean overall anterior
      displacement of the anterior laminar surface, while eyes with mild glaucoma and
      healthy eyes showed a posterior displacement of the LC during IOP elevation. The
      CH decreased significantly from baseline only in eyes with severe glaucoma, but
      the CRF increased significantly in all glaucomatous eyes. The CRF increase
      correlated with the anterior displacement of the LC in eyes with severe glaucoma.

PMID- 29588570
TI  - Pneumatic retinopexy: patient selection and specific factors.
AB  - Pneumatic retinopexy is a minimally invasive, non-incisional procedure for
      repairing retinal detachment. This procedure is associated with reduced
      morbidity, reduced cost and faster postoperative recovery compared to pars plana
      vitrectomy and scleral buckling. Superior visual acuity outcomes have also been
      reported. Intraoperative complications are primarily related to the intraocular
      pressure rise caused by gas injection, or the misdirection of the gas. There is a
      low rate of postoperative complications. Anatomic success rates of over 90% can
      be achieved when strict selection criteria are applied. However, a number of
      studies have revealed good outcomes in cases with expanded clinical indications.
      Pneumatic retinopexy is currently underutilized. With appropriate patient
      selection, a high success rate can be achieved, and therefore, this procedure has
      an important role in the armamentarium of the vitreoretinal surgeon.

PMID- 29588571
TI  - Comparisons of foveal thickness and slope after macular hole surgery with and
      without internal limiting membrane peeling.
AB  - Background: We have shown that the foveal contour was asymmetrical after
      idiopathic macular hole (MH) closure by pars plana vitrectomy (PPV) with internal
      limiting membrane (ILM) peeling. The purpose of this study was to determine
      whether these morphological changes differ in eyes after PPV without ILM peeling.
      Methods: Ten eyes of 10 patients that underwent PPV without ILM peeling and 12
      eyes of 11 patients with ILM peeling were studied. The MH in all eyes was <400 um
      in diameter. Six months after the PPV, the macular thickness and foveal slope
      around the closed MH were determined by spectral-domain optical coherence
      tomography. The thickness of the ganglion cell complex was measured by another
      spectral-domain optical coherence tomography instrument >6 months after the
      surgery. Results: The mean parafoveal retinal thickness in the non-peeled group
      was 367.1 um in the nasal (N), 353.0 um in the temporal (T), 366.9 um in the
      superior (S), and 357.3 um in the inferior (I) sectors. The T, S, and I sectors
      were significantly thicker than the corresponding sectors in the ILM peeled group
      (p=0.0008, 0.003, and 0.03, respectively). The mean ganglion cell complex was
      thicker not only in the N sector but also in the T sector in the non-peeled
      group. The mean retinal slopes in the non-peeled group (N, 40.2 degrees ; T, 37.6
      degrees ; S, 41.2 degrees ; I, 39.5 degrees ) were flatter than those in the
      peeled group (N, 52.3 degrees ; T, 43.6 degrees ; S, 50.8 degrees ; I, 51.9
      degrees ; p=0.009, 0.09, 0.008, and 0.017, respectively). Conclusion: The
      symmetrical fovea after MH surgery in the non-ILM peeled eyes indicates that the
      asymmetrical fovea after ILM peeling was probably due to the ILM peeling.

PMID- 29588572
TI  - Effect of tocotrienol from Bixa orellana (annatto) on bone microstructure,
      calcium content, and biomechanical strength in a model of male osteoporosis
      induced by buserelin.
AB  - Background: Patients receiving androgen deprivation therapy experience secondary
      hypogonadism, associated bone loss, and increased fracture risk. It has been
      shown that tocotrienol from Bixa orellana (annatto) prevents skeletal
      microstructural changes in rats experiencing primary hypogonadism. However, its
      potential in preventing bone loss due to androgen deprivation therapy has not
      been tested. This study aimed to evaluate the skeletal protective effects of
      annatto tocotrienol using a buserelin-induced osteoporotic rat model. Methods:
      Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups.
      The baseline control (n=6) was sacrificed at the onset of the study. The normal
      control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and
      normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin
      control (n=8) received corn oil orally daily and subcutaneous buserelin injection
      (75 ug/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in
      drinking water and daily subcutaneous buserelin injection (75 ug/kg). The
      remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100
      mg/kg (n=8) plus daily subcutaneous buserelin injection (75 ug/kg) (n=8). At the
      end of the experiment, the rats were euthanized and their blood, tibia, and femur
      were harvested. Structural changes of the tibial trabecular and cortical bone
      were examined using X-ray micro-computed tomography. Femoral bone calcium content
      and biomechanical strength were also evaluated. Results: Annatto tocotrienol at
      60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and
      cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto
      tocotrienol also improved femoral biomechanical strength and bone calcium content
      in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were
      comparable to calcium supplementation. Conclusion: Annatto tocotrienol
      supplementation is effective in preventing degeneration of the bone induced by
      buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving
      androgen deprivation therapy.

PMID- 29588574
TI  - Application of health quotient to enhance chronic periodontitis treatments.
AB  - Objectives: Based on the concept of health quotient (HQ), we designed and
      facilitated personalized plans to improve patients' compliance and oral health.
      The study aims to increase HQ level of patients with chronic periodontitis from
      four aspects, namely self-care, health knowledge, lifestyle, and mental health,
      and evaluate the effects of HQ training in maintaining oral health. Method: In
      total, 105 patients with chronic periodontitis were recruited from Capital
      Medical University-Affiliated Beijing Chaoyang Hospital from January 2015 to
      January 2017. The patients were randomly split into two groups (control versus
      test). All the patients received standard periodontal treatments. In addition,
      patients in the control group received conventional oral health instructions, and
      patients in the test group received the HQ training. At the end of the training,
      oral health status of both groups was evaluated and recorded. Results: The oral
      health status and the HQ scores were significantly better in the test group than
      the control group (P<0.01). The training in HQ provided a better guidance for
      patients in oral health maintenance and further improved patients' compliance.
      Conclusion: HQ training for patients with chronic periodontitis increased their
      scores in self-care and health knowledge and significantly slowed down the
      progression of chronic periodontitis.

PMID- 29588573
TI  - Vitexin protects dopaminergic neurons in MPTP-induced Parkinson's disease through
      PI3K/Akt signaling pathway.
AB  - : Parkinson's disease (PD) is a progressive neurodegenerative disease which is
      characterized by the degeneration of dopaminergic neurons in the substantia nigra
      pars compacta (SNpc). Methods: In this study, the neuroprotective effect of
      vitexin (Vit), a flavonoid compound isolated from Crataegus pinnatifida Bunge was
      examined in PD models both in vitro and in vivo. Results: On SH-SY5Y cells,
      methyl-4-phenylpyridine (MPP+) treatment suppressed cell viability, induced
      apoptosis, and increased Bax/Bcl-2 ratio and caspase-3 activity. However, Vit
      improved these parameters induced by MPP+ treatment significantly. Further study
      disclosed that Vit enhanced the phosphorylation of PI3K and Akt which was
      downregulated by MPP+ in SH-SY5Y cells, the effect of which could be blocked by
      PI3K inhibitor LY294002 and activated by PI3K activator IGF-1. Moreover, results
      from the pole test and traction test suggested that Vit pretreatment prevented
      bradykinesia and alleviated the initial lesions caused by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) in MPTP-treated mouse PD model. Vit also
      enhanced the activation of PI3K and Akt and suppressed the ratio of Bax/Bcl-2 and
      caspase-3 activity in MPTP-treated mice. Conclusion: Taken together, this study
      demonstrated that Vit protected dopaminergic neurons against MPP+/MPTP-induced
      neurotoxicity through the activation of PI3K/Akt signaling pathway. Our findings
      may facilitate the clinical application of Vit in the therapy of PD.

PMID- 29588575
TI  - Measuring the importance of health domains in psoriasis - discrete choice
      experiment versus rating scales.
AB  - Background: Psoriasis affects different aspects of health-related quality of life
      (eg, physical, psychological, and social impairments); these health domains can
      be of different importance for patients. The importance of domains can be
      measured with the Patient Benefit Index (PBI). This questionnaire weights the
      achievement of treatment goals by Likert scales (0, "not important at all" to 4,
      "very important") using the Patient Needs Questionnaire (PNQ). Treatment goals
      assessed with the PBI have been assigned to five health domains; the importance
      of each domain can be calculated as the average importance of the respective
      treatment goals. In this study, the PBI approach of deriving importance weights
      is contrasted to a discrete choice experiment (DCE), in order to determine the
      importance of health domains in psoriasis, and to find if the resulting weights
      will differ when derived from these two methods. Methods: Adult patients with
      psoriasis completed both questionnaires (PNQ, DCE). The PBI domains were used as
      attributes in the DCE with the levels "did not help at all", "helped moderately",
      and "helped a lot". Results: Using DCE, "improving physical functioning" was the
      most important health domain, followed by "improving psychological well-being".
      Using PNQ, these domains were ranked in position two and three following
      "strengthening confidence in the therapy and in a possible healing". The latter
      was least important using DCE. The only agreement of ranking was shown in
      "reducing impairments due to therapy" (position four). "Improving social
      functioning" was ranked in position three (DCE) and five (PNQ). Conclusion:
      Health domains have different importance to patients with psoriasis. Using PNQ or
      DCE to determine the importance of domains results in markedly different
      rankings; both approaches can thus not be considered equivalent. However, in this
      study, importance was assessed at the domain level in DCE and at the single item
      level in PNQ, which may have added to the differences.

PMID- 29588577
TI  - The level of awareness and the attitude of patients recommended for use of
      compression stockings in Turkish society, and investigation of the factors
      affecting their use.
AB  - Objective: The purpose of this study was to reveal the treatment outlook, usage
      habits, and factors affecting these habits, in addition to providing suggestions
      for solutions for patients who are frequently recommended the use of compression
      stockings as treatment for conditions such as chronic venous insufficiency, deep
      vein thrombosis, lymphedema, and pregnancy. Methods: The study was conducted as a
      face-to-face questionnaire session with 1,004 patients who had previously
      registered at the cardiovascular surgeon's polyclinic of Sivas Numune Hospital
      between March 29, 2017, and October 31, 2017. In the study, basic criteria such
      as the patients' history, physical examination findings, and the use of
      compression stockings were evaluated. The survey was conducted in patients who
      were recommended compression stockings treatment for conditions such as chronic
      venous insufficiency, deep vein thrombosis, lymphedema, or pregnancy. The
      patients were asked about their demographics, characteristics of the compression
      stockings, whether compression stockings were used or not, and doctor evaluations
      related to the diagnosis. Results: At the end of the study, it was found that
      20.5% of the patients who were recommended compression stockings never bought
      them and only 11.5% of the patients regularly used them. Another surprising
      detail was that only 54.7% of the patients thought that the compression stockings
      were part of the treatment and 44.0% of the patients thought that they would
      benefit from using them. Conclusion: In many guidelines, use of compression
      stockings is the cornerstone of treatment of venous diseases. However, when the
      treatment incompatibility of the patients is taken into account, many duties fall
      to the doctors. The first of these is to inform the patient about the treatment
      and to answer any questions from the patients. In addition, the socioeconomic and
      sociocultural status of patients should be considered by the doctors.

PMID- 29588576
TI  - A 4-year non-randomized comparative phase-IV study of early rheumatoid arthritis:
      integrative anthroposophic medicine for patients with preference against DMARDs
      versus conventional therapy including DMARDs for patients without preference.
AB  - Background: While disease-modifying antirheumatic drugs (DMARDs) are a mainstay
      of therapy for rheumatoid arthritis (RA), some patients with early RA refuse
      DMARDs. In anthroposophic medicine (AM), a treatment strategy for early RA
      without DMARDs has been developed. Preliminary data suggest that RA symptoms and
      inflammatory markers can be reduced under AM, without DMARDs. Patients and
      methods: Two hundred and fifty-one self-selected patients aged 16-70 years,
      starting treatment for RA of <3 years duration, without prior DMARD therapy,
      participated in a prospective, non-randomized, comparative Phase IV study. C
      patients were treated in clinics offering conventional therapy including DMARDs,
      while A-patients had chosen treatment in anthroposophic clinics, without DMARDs.
      Both groups received corticosteroids and nonsteroidal anti-inflammatory drugs
      (NSAIDs). Primary outcomes were intensity of RA symptoms measured by self-rating
      on visual analog scales, C-reactive protein, radiological progression, study
      withdrawals, serious adverse events (SAE), and adverse drug reactions in months 0
      48. Results: The groups were similar in most baseline characteristics, while A
      patients had longer disease duration (mean 15.1 vs 10.8 months, p<0.0001),
      slightly more bone destruction, and a much higher proportion of women (94.6% vs
      69.7%, p<0.0001). In months 0-12, corticosteroids were used by 45.7% and 81.6%
      (p<0.0001) and NSAIDs by 52.8% and 68.5% (p=0.0191) of A- and C-patients,
      respectively. During follow-up, both groups not only had marked reduction of RA
      symptoms and C-reactive protein, but also some radiological disease progression.
      Also, 6.2% of A-patients needed DMARDs. Apart from adverse drug reactions (50.4%
      and 69.7% of A- and C-patients, respectively, p=0.0020), none of the primary
      outcomes showed any significant between-group difference. Conclusion: Study
      results suggest that for most patients preferring anthroposophic treatment,
      satisfactory results can be achieved without use of DMARDs and with less use of
      corticosteroids and NSAIDs than in conventional care. Limitation: Because of the
      non-randomized study design, with A-patients choosing anthroposophic treatment,
      one cannot infer how this treatment would have worked for C-patients.

PMID- 29588578
TI  - Investigating the role of perception of aging and associated factors in death
      anxiety among the elderly.
AB  - Background and objectives: The world's growing elderly population highlights the
      necessity for further attention to the psychological problems of the elderly,
      such as death anxiety. Analysis of the elderly's perception of aging and
      associated factors can contribute to prediction of their future physical and
      mental health. The purpose of this study was to determine the relationship of
      perception of aging, and a group of demographic factors, with death anxiety in
      the elderly living in Gonabad, Iran. Subjects and methods: This analytical
      descriptive study was conducted on 330 elderly residents of Gonabad, who were
      selected by stratified random sampling. Research tools were a standard
      demographic questionnaire, Barker's Brief Aging Perceptions Questionnaire, and
      Collett-Lester Fear of Death Scale. Data were collected by interview of
      respondents at their home. Data analysis was carried out in SPSS 16 using
      descriptive statistics, analysis of variance, Pearson's test, independent t-test,
      and linear regression. Results: Respondents had a mean age of 73.97+/-7.68 years,
      42.4% of respondents were men and 57.6% were women. The total Barker's Brief
      Aging Perceptions Questionnaire score was 63.18+/-8.75, with the highest score
      (17.10+/-4.70) associated with negative consequences and control. The total
      Collett-Lester Fear of Death Scale score was 128+/-14.80, with the highest score
      (35.13+/-4.06) pertaining to the subscale fear of other people's death.
      Regression results indicated that the death anxiety score was predictable
      according to the age and all dimensions of perception of aging, except for the
      consequences and negative control dimension. Conclusion: Age and the perception
      of aging are good predictors of death anxiety. The authors recommend further
      research on the determinants of death anxiety in the elderly and the development
      of a comprehensive care plan to reduce this anxiety among Iranian elderly.

PMID- 29588579
TI  - Resistance training-induced gains in muscle strength, body composition, and
      functional capacity are attenuated in elderly women with sarcopenic obesity.
AB  - Objectives: The purpose of this study was to compare the effects of resistance
      training (RT) on body composition, muscle strength, and functional capacity in
      elderly women with and without sarcopenic obesity (SO). Methods: A total of 49
      women (aged >=60 years) were divided in two groups: without SO (non-SO, n=41) and
      with SO (n=8). Both groups performed a periodized RT program consisting of two
      weekly sessions for 16 weeks. All measures were assessed at baseline and
      postintervention, including anthropometry and body composition (dual-energy X-ray
      absorptiometry), muscle strength (one repetition maximum) for chest press and 45
      degrees  leg press, and functional capacity (stand up, elbow flexion, timed "up
      and go"). Results: After the intervention, only the non-SO group presented
      significant reductions in percentage body fat (-2.2%; P=0.006), waist
      circumference (-2.7%; P=0.01), waist-to-hip ratio (-2.3; P=0.02), and neck
      circumference (-1.8%; P=0.03) as compared with baseline. Muscle strength in the
      chest press and biceps curl increased in non-SO only (12.9% and 11.3%,
      respectively), while 45 degrees  leg press strength increased in non-SO (50.3%)
      and SO (40.5%) as compared with baseline. Performance in the chair stand up and
      timed "up and go" improved in non-SO only (21.4% and -8.4%, respectively),
      whereas elbow flexion performance increased in non-SO (23.8%) and SO (21.4%).
      Effect sizes for motor tests were of higher magnitude in the non-SO group, and in
      general, considered "moderate" compared to "trivial" in the SO group. Conclusion:
      Results suggest that adaptations induced by 16 weeks of RT are attenuated in
      elderly woman with SO, compromising improvements in adiposity indices and gains
      in muscle strength and functional capacity.

PMID- 29588580
TI  - A functional SNP upstream of the ADRB2 gene is associated with COPD.
AB  - Background: Previous studies have suggested that beta2-adrenergic receptor
      (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in
      ADRB2 on COPD has not been evaluated yet. Methods: In this study, SNaPshot
      genotyping, luciferase assay, chromatin immunoprecipitation and real-time
      polymerase chain reaction were adopted to investigate the association between
      ADRB2 genetic polymorphisms and COPD, comprehensively. Results: One single
      nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a
      significant association with COPD by the logistic regression analysis after
      adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222
      controls from southwest Chinese population. Furthermore, the luciferase assay
      indicated that rs12654778-A allele reduced the relative promoter activity by ~26%
      compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation
      analysis demonstrated that rs12654778 modulated the binding affinity of
      transcription factor neurofibromin 1. In addition, a significantly reduced
      expression of ADRB2 in COPD patients was observed, compared with normal controls
      (p=0.017). Conclusion: Our findings suggest a previously unknown mechanism
      linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset,
      for the first time.

PMID- 29588581
TI  - Maintenance inhaler preference, attribute importance, and satisfaction in
      prescribing physicians and patients with asthma, COPD, or asthma-COPD overlap
      syndrome consulting for routine care.
AB  - Background: In respiratory disorders, patient- and physician-perceived
      satisfaction with the maintenance inhaler device is an important factor driving
      treatment compliance and outcomes. We examine inhaler preferences in asthma and
      COPD from patient and physician perspectives, particularly focusing on the
      relative importance of individual device attributes and patient characteristics
      guiding inhaler choice. Materials and methods: Real-world data from >7,300
      patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS) consulting for
      routine care were derived from respiratory Disease Specific Programs conducted in
      Europe, USA, Japan, and China. Outcome variables included current pattern of
      inhaled maintenance therapy and device type, physician preference, patient
      reported device attribute importance, and satisfaction. Results: The most
      commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS
      were dry powder inhalers (62.8%-88.5% of patients) and pressurized metered dose
      inhalers (18.9%-35.3% of patients). One-third of physicians stated no preference
      for maintenance device when prescribing treatment, and less than one-third of
      patients reported being "extremely satisfied" with any attribute of their device.
      Instructions being "simple and easy to follow" was the inhaler attribute most
      commonly selected as important. For approximately one-third of patients across
      all groups, "ease of use/suitability of inhaler device" was a reason for the
      prescribing decision, as stated by the physician. Device characteristics were
      more likely to impact the prescribing decision in older patients (in asthma and
      COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001).
      Conclusion: A relatively high proportion of physicians had no preference for
      inhaler type across asthma, COPD, and ACOS. Simplicity of use was the most
      important inhaler attribute from a patient's perspective. Physicians appeared to
      place most importance on ease of use and device suitability when selecting
      inhalers for older patients and those with more severe disease, particularly in
      COPD.

PMID- 29588582
TI  - Influence of luminescent graphene quantum dots on trypsin activity.
AB  - Background: Protein-graphene interactions have the potential to play a pivotal
      role in the future directions of nanomedicine. These interactions lead to diverse
      processes such as generation of protein coronas, nano-bio interfaces, particle
      wrapping, and biocatalytic processes that could determine the ultimate fate of
      graphene nanocomposites in biologic systems. However, such interactions and their
      effects on the bioavailability of graphene have not yet been widely appreciated,
      despite the fact that this is the primary surface in contact with cells. Methods:
      This paper reports on the integrative physiochemical interaction between trypsin
      and graphene quantum dots (GQDs) to determine their potential biologic identity
      in enzyme engineering. This interaction was measured by a wide range of
      analytical methods. Results: Definitive binding and modulation of trypsin-GQDs
      was demonstrated for the first time by use of vibrational spectroscopy and
      wetting transparency, which revealed that trypsin was absorbed on GQDs' surface
      through its cationic and hydrophilic residues. Our findings suggested that
      trypsin's active sites were stabilized and protected by the GQDs, which were
      likely to be responsible for the high bioavailability of GQDs in enzymes.
      Conclusion: Our work demonstrates the efficacy of GQDs as an enzyme modulator
      with high specificity, and their great application potential in enzyme
      engineering as well as enzyme-based therapies.

PMID- 29588583
TI  - siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced
      hepatocellular carcinoma therapy.
AB  - Background: Small interfering RNA (siRNA) as a new therapeutic modality holds
      promise for cancer treatment. However, the traditional viral carriers are prone
      to immunogenicity and risk of insertional mutagenesis. Methods: In order to
      provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the
      hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was
      fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking
      the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The
      siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic
      interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se
      PEI@siRNA. Results: The HA-Se-PEI@siRNA was internalized into the HepG2 cell
      mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor
      targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher
      transfection efficiency, greater gene silencing ability, and stronger
      cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se
      PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA
      induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis.
      Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor
      efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA
      Se-PEI@siRNA was almost no toxic to the key organs of mice. Conclusion: These
      findings provided an alternative therapeutic route for targeted cancer
      treatments.

PMID- 29588584
TI  - A novel electrospun-aligned nanoyarn/three-dimensional porous nanofibrous hybrid
      scaffold for annulus fibrosus tissue engineering.
AB  - Introduction: Herniation of the nucleus pulposus (NP) because of defects in the
      annulus fibrosus (AF) is a well-known cause of low back pain. Defects in the AF
      thus remain a surgical challenge, and efforts have been made to develop new
      techniques for closure and repair. In this study, we developed an electrospun
      aligned nanoyarn scaffold (AYS) and nanoyarn/three-dimensional porous nanofibrous
      hybrid scaffold (HS) for AF tissue engineering. Methods: The AYS was fabricated
      via conjugated electrospinning, while the aligned nanofibrous scaffold (AFS) was
      prepared by traditional electrospinning as a baseline scaffold. The HS was
      constructed by freeze-drying and cross-linking methods. Scanning electron
      microscopy and mechanical measurement were used to characterize the properties of
      these scaffolds. Bone marrow derived mesenchymal stem cells (BMSCs) were seeded
      on scaffolds, and cell proliferation was determined by CCK-8 assay, while cell
      infiltration and differentiation were assessed by histological measurement and
      quantitative real-time polymerase chain reaction, respectively. Results:
      Morphological measurements showed that AYS presented a relatively better three
      dimensional structure with larger pore sizes, higher porosity, and better fibers'
      alignment compared to AFS. Mechanical testing demonstrated that the tensile
      property of AFS and AYS was qualitatively similar to the native AF tissue, albeit
      to a lesser extent. When BMSCs were seeded and cultured on these scaffolds, the
      number of cells cultured on HS and AYS was found to be significantly higher than
      that on AFS and culture plate after 7 days of culture (P<0.05). In addition, cell
      infiltration was significantly higher in HS when compared with AFS and AYS
      (P<0.05). A part of BMSCs ingressed into the inner part of AYS upon long-term in
      vitro culture. No significant difference was observed between AFS and AYS in
      terms of the median infiltration depth (P>0.05). BMSCs seeded on AYS demonstrated
      an increased expression of COL1A1, while the expression levels of SOX-9, COL2A1,
      and Aggrecan were higher in HS compared to other scaffolds (P<0.05). Conclusion:
      These findings indicate that HS makes a proper scaffold for the AF tissue
      engineering as it replicates the axial compression and tensile property of AF,
      thereby providing a better platform for cell infiltration and cell-scaffold
      interaction.

PMID- 29588586
TI  - Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin
      E succinate conjugates for improved lung cancer treatment.
AB  - Background: Lung cancer is the primary cause of cancer-related death worldwide. A
      redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery
      and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for
      improved lung cancer treatment. Methods: The redox-sensitive nanocarrier system
      constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV)
      conjugate was synthesized and PTX was loaded in the delivery system. The
      physicochemical properties of the HSV nanoparticles were characterized. The redox
      sensitivity, tumor-targeting and intracellular drug release capability of the HSV
      nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor
      activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over
      expressed A549 tumor model. Results: This HSV conjugate was successfully
      synthesized and self-assembled to form nanoparticles in aqueous condition with a
      low critical micelle concentration of 36.3 MUg mL-1. Free PTX was successfully
      entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and
      an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV
      nanoparticles was confirmed by particle size change of the nanoparticles along
      with in vitro release profiles in different reducing environment. In addition,
      the HA-receptor mediated endocytosis and the potency of redox-sensitivity for
      intracellular drug delivery were further verified by flow cytometry and confocal
      laser scanning microscopic analysis. The antitumor activity results showed that
      compared to redox-insensitive nanoparticles and Taxol(r), PTX-loaded redox
      sensitive nanoparticles exhibited much greater in vitro cytotoxicity and
      apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo,
      the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an
      A549 mouse xenograft model and demonstrated improved safety profile. In summary,
      our PTX-loaded redox-sensitive HSV nanoparticles demonstrated enhanced antitumor
      efficacy and improved safety of PTX. Conclusion: The results of our study
      indicated the redox-sensitive HSV nanoparticle was a promising nanocarrier for
      lung cancer therapy.

PMID- 29588587
TI  - Targeted therapy of intracranial glioma model mice with curcumin nanoliposomes.
AB  - Background: Glioma is the most aggressive and lethal brain tumor in humans, it
      comprises about 30 per cent of all brain tumors and central nervous system
      tumors. Purpose: The objective of this study was to create novel brain-targeting
      nanoliposomes to encapsulate curcumin as a promising option for glioma therapy.
      Patients and methods: Human glioma cells (U251MG) were used to determine cell
      uptake efficiency and possible internalization mechanism of the curcumin-loaded
      nanoliposomes modified by a brain-targeting peptide RDP. In addition,
      intracranial glioma mice model was prepared by transplantation of U251MG cells
      into the mice striatum, and then the liposomes were intravenously administered
      into the glioma-bearing mice to evaluate the anti-glioma activity. Results: RDP
      modified liposomes (RCL) could enter the brain and glioma region, and were
      internalized by the glioma cells perhaps through acetylcholine receptor-mediated
      endocytosis pathway. Furthermore, the RCL prolonged the survival time of the
      glioma-bearing mice from 23 to 33 days, and the inhibition mechanism of the RCL
      on glioma cell was partly due to cell cycle arrest at the S phase and induction
      of cell apoptosis. Conclusion: This study would provide a potential approach for
      targeted delivery of drug-loaded liposomes for glioma treatment.

PMID- 29588585
TI  - Recent developments in solid lipid nanoparticle and surface-modified solid lipid
      nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in
      various chronic diseases.
AB  - Solid lipid nanoparticle (SLN) delivery systems have a wide applicability in the
      delivery of phyto-bioactive compounds to treat various chronic diseases,
      including diabetes, cancer, obesity and neurodegenerative diseases. The multiple
      benefits of SLN delivery include improved stability, smaller particle size,
      leaching prevention and enhanced lymphatic uptake of the bioactive compounds
      through oral delivery. However, the burst release makes the SLN delivery systems
      inadequate for the oral delivery of various phyto-bioactive compounds that can
      treat such chronic diseases. Recently, the surface-modified SLN (SMSLN) was
      observed to overcome this limitation for oral delivery of phyto-bioactive
      compounds, and there is growing evidence of an enhanced uptake of curcumin
      delivered orally via SMSLNs in the brain. This review focuses on different SLN
      and SMSLN systems that are useful for oral delivery of phyto-bioactive compounds
      to treat various chronic diseases.

PMID- 29588588
TI  - Tri-block polymer with interfacial layer formation ability and its use in
      maintaining supersaturated drug solution after dissolution of solid dispersions.
AB  - Background: Maintaining a supersaturated drug solution after the dissolution of
      the solid dispersions of water insoluble drugs continues to be a great challenge
      and is important to the oral bioavailability enhancement of hardly soluble drugs.
      Methods: Nimodipine solid dispersions were prepared by hot-melt extrusion and a
      special tri-block polymer was employed as a co-carrier. The solid dispersions
      were characterized by modulated differential scanning calorimetry, transmission
      electron microscopy, hydrogen-nuclear magnetic resonance and so on. Results: The
      tri-block polymer was able to inhibit the formation of drug crystals after
      dissolution of the solid dispersions. Due to the unique interfacial layer
      formation ability of the tri-block polymer, a special drug loading micelle which
      encapsulated the compound and the hydrophobic fragments of the copolymers
      appeared in the release media. The tri-block polymer was composed of a
      hydrophilic part forming the shell of micelles, a hydrophobic part shaping the
      core of micelles, and a special intermediate hydrophilicity part constructing the
      interfacial layer of micelles. Conclusion: The tri-block polymer was not only
      able to stabilize the supersaturated drug solution of solid dispersions to
      enhance the oral bioavailability of hardly soluble drugs, but is also a potential
      candidate to construct micelles for systemic administration, due to the good
      compatibility and organic solvents free micelle formation procedure.

PMID- 29588589
TI  - Hepatocellular carcinoma-targeted effect of configurations and groups of
      glycyrrhetinic acid by evaluation of its derivative-modified liposomes.
AB  - Background: There are abundant glycyrrhetinic acid (GA) receptors on the cellular
      membrane of hepatocytes and hepatocellular carcinoma (HCC) cells. The receptor
      binding effect might be related to the structure of the guiding molecule. GA
      exists in two stereoisomers with C3-hydroxyl and C11-carbonyl active groups.
      Purpose: The objective of this study was to investigate the relationship between
      the HCC-targeted effect and the configurations and groups of GA. Methods and
      results: Different GA derivatives (18beta-GA, 18alpha-GA, 3-acetyl-18beta-GA [3
      Ace-GA] and 11-deoxy-18beta-GA [11-Deo-GA]) were used to investigate the
      targeting effect of GA's configurations and groups on HCC cells. The EC50 values
      of competition to binding sites and the ratio of specific binding in HepG2 cells
      showed that 18beta-GA and 3-Ace-GA demonstrated significant competitive effect
      with fluorescein isothiocyanate (FITC)-labeled GA. Then, the GA derivatives were
      distearoyl-phosphatidylethanolamine (DSPE)-PEGylated. 18beta-GA-, 18alpha-GA-, 3
      Ace-GA-and 11-Deo-GA-modified liposomes were prepared and characterized by size,
      zeta potential, encapsulation efficiency, loading capacity, leakage and membrane
      stability. Evaluation on the cellular location in vitro and tumor targeting in
      vivo was carried out. Compared to common long-circulation liposome (PEG-Lip),
      more 18beta-GA- and 3-Ace-GA-modified liposomes aggregated around HepG2 cells in
      vitro in short time and transferred into HCC tumors in vivo for a longer time.
      Conclusion: The beta-configuration hydrogen atom on C18 position of GA played the
      most important role on the targeting effect. C11-carbonyl and C3-hydroxy groups
      of GA have certain and little influence on targeting action to HCC, respectively.
      In general, GA might be a promising targeting molecule for the research on liver
      diseases and hepatoma therapy.

PMID- 29588592
TI  - Continuous performance task in ADHD: Is reaction time variability a key measure?
AB  - Objective: To compare the use of the Continuous Performance Task (CPT) reaction
      time variability (intraindividual variability or standard deviation of reaction
      time), as a measure of vigilance in attention-deficit hyperactivity disorder
      (ADHD), and stimulant medication response, utilizing a simple CPT X-task vs an A
      X-task. Method: Comparative analyses of two separate X-task vs A-X-task data
      sets, and subgroup analyses of performance on and off medication were conducted.
      Results: The CPT X-task reaction time variability had a direct relationship to
      ADHD clinician severity ratings, unlike the CPT A-X-task. Variability in X-task
      performance was reduced by medication compared with the children's unmedicated
      performance, but this effect did not reach significance. When the coefficient of
      variation was applied, severity measures and medication response were significant
      for the X-task, but not for the A-X-task. Conclusion: The CPT-X-task is a useful
      clinical screening test for ADHD and medication response. In particular, reaction
      time variability is related to default mode interference. The A-X-task is less
      useful in this regard.

PMID- 29588591
TI  - Immobilization of a carbon nanomaterial-based localized drug-release system using
      a bispecific material-binding peptide.
AB  - Introduction: Inorganic materials are widely used in medical devices, such as
      artificial hearts, vessels, and joints, in stents, and as nanocarriers for drug
      delivery systems. Carbon nanomaterials are of particular interest due to their
      biological inertness and their capability to accommodate molecules. Several
      attempts have been proposed, in which carbon nanomaterials are used as
      nanocarriers for the systemic delivery of drugs. Materials and methods: We
      developed a drug-delivery system in which oxidized single-walled carbon nanohorns
      (oxSWNHs) were immobilized on a titanium (Ti) surface using material-binding
      peptides to enable localized drug delivery. For this purpose, we utilized a
      bispecific peptidic aptamer comprising a core sequence of a Ti-binding peptide
      and a SWNH-binding peptide to immobilize oxSWNHs on Ti. Results: Scanning
      electron microscopy was used to confirm the presence of oxSWNHs adsorbed onto the
      Ti surface, and a quartz crystal microbalance was used to evaluate the binding
      process during oxSWNH adsorption. The oxSWNHs-ornamented Ti substrate was
      nontoxic to cells and released biologically active dexamethasone over a sustained
      period. Conclusion: This oxSWNHs-immobilized system can be used to modify the
      surface of Ti in implants and be loaded with drugs that stimulate osteogenesis
      and bone regeneration.

PMID- 29588590
TI  - Polymer nanofiber-based microchips for EGFR mutation analysis of circulating
      tumor cells in lung adenocarcinoma.
AB  - Background: Circulating tumor cells (CTCs) detection, an approach considered to
      be "liquid biopsy", is a potential alternative method in clinical use for early
      diagnosis of solid tumor progression. Methods: In this study, we developed a poly
      (lactic-co-glycolic acid) (PLGA) - nanofiber (PN)-NanoVelcro chip as an efficient
      device for simple and rapid capture of CTCs from peripheral blood. We evaluated
      the device performance by assessing the capture efficiency and purity. Single CTC
      was isolated via laser microdissection system for subsequent genetic analysis,
      with an aim to find the concordance of epidermal growth factor receptor (EGFR)
      mutations between tumor tissue and CTCs. Results: PN-NanoVelcro chip exhibits
      great performance in capture efficiency and high purity. The genetic analysis
      results showed that most EGFR mutation in tumor tissue could also be detected in
      CTCs. Conclusion: Compared to computed tomography image results, CTC detection
      can be implemented throughout the course of diseases and provides an accurate and
      earlier diagnosis of tumor progression, which make it possible for patients to
      acquire suitable and timely treatment.

PMID- 29588593
TI  - Beneficial effects of trimetazidine on expression of serotonin and serotonin
      transporter in rats with myocardial infarction and depression.
AB  - Background: Trimetazidine is an anti-ischemic drug that can inhibit platelet
      aggregation and regulate serotonin (5-hydroxytryptamine [5-HT]) release. The
      purpose of this study was to investigate the therapeutic effects of trimetazidine
      on 5-HT and serotonin transporter (SERT) expression in experimentally induced
      myocardial infarction (MI), depression, and MI + depression. Materials and
      methods: Eighty Sprague Dawley (SD) rats were randomly divided into a
      trimetazidine group and a saline group of 40 rats each. The trimetazidine group
      was given trimetazidine pretreatment for 4 weeks, while the saline group received
      saline for 4 weeks. Both groups were then subdivided into four subgroups (n=10),
      which were each subjected to a unique disease condition: sham surgery, MI,
      depression, or MI + depression. All rats were sacrificed 3 days thereafter, and
      serum and platelet levels of 5-HT and SERT were assessed. In addition, we
      experimented with trimetazidine posttreatment. Twenty SD rats underwent MI
      surgery, and were then randomly divided into a treatment and a saline group (n=10
      each). For 4 weeks post-surgery, the trimetazidine group was given trimetazidine,
      while the saline group received saline. Serum and platelet levels of 5-HT and
      SERT were assessed. Results: Pretreatment with trimetazidine: in the nontreatment
      saline group, MI, depression, and MI + depression showed significant declines
      (P<0.05) in both serum and platelet 5-HT levels compared to sham. Trimetazidine
      treatment significantly increased serum and platelet 5-HT levels in the MI,
      depression, and MI + depression (P<0.05) subgroups compared to their counterparts
      in the saline group. Results for SERT were heterogeneous between serum and
      platelets. Trimetazidine treatment significantly decreased serum levels of SERT
      in the sham surgery subgroup (P<0.05), while significantly increasing levels in
      depression rats, compared to control (P<0.05). In platelets, trimetazidine
      significantly decreased SERT in sham surgery, MI, depression, and MI + depression
      rats, compared to control (P<0.05). This contrast suggests that trimetazidine has
      opposite effects in serum and platelet SERT levels for the three disease models.
      Post-surgery trimetazidine: increased serum 5-HT (P<0.05) and serum SERT (P<0.05)
      were observed, compared to control. In platelets, trimetazidine decreased both 5
      HT and SERT compared to control, significantly (P<0.05) for 5-HT, but not
      significantly for SERT (P>0.05). Conclusion: Trimetazidine has a regulatory
      effect on 5-HT and SERT in the serum and platelets. Because of the downstream
      effects of this regulation on blood vessel function and myocardial protection,
      trimetazidine may be a therapeutic or preventive agent in several disease
      processes, including MI, depression, and the comorbidity between these two
      diseases. Further investigation, aimed at exploring the clinical potential of
      trimetazidine, is therefore warranted.

PMID- 29588594
TI  - The quantification and assessment of depression and anxiety in patients with
      postoperative gastroparesis syndrome.
AB  - Background: This study aimed to analyze the stage-situation depression and
      anxiety as well as independent influential factors in patients with postsurgical
      gastroparesis syndrome (PGS) and to provide dependent indications for treatment.
      Patients and methods: The self-rating depression scale (SDS) and self-rating
      anxiety scale (SAS) were used to test the depression and anxiety of 53 patients
      with PGS, who were treated in the Department of Gastroenterological Surgery of
      Gansu Provincial Hospital from January 2012 to October 2016. A comparison between
      the SDS or SAS scores of patients with PGS and without PGS was undertaken; then,
      we retrospectively analyzed the factors influencing depression and anxiety in PGS
      patients. Results: The patients with PGS' mean scores of depression and anxiety
      were 49.92+/-11.37 and 50.91+/-6.57, respectively, which were higher than that of
      patients without PGS in the Chinese population (P<0.05). The results of
      multivariate logistic regression analysis indicated that the independent
      influential factors of depression and anxiety in patients with PGS included
      course of disease, pancreatic juice leakage, preoperative outflow tract
      obstruction, postoperative abdominal infection, and anastomotic complication
      (P<0.05). Patients with a disease course longer than 30 days; with pancreatic
      juice leakage; and who suffered from preoperative outflow tract obstruction,
      postoperative abdominal infection, and anastomotic complication had higher ratios
      of depression and anxiety. Conclusion: Depression and anxiety are clearly evident
      in patients with PGS, and we should pay attention to this phenomenon and provide
      appropriate treatment.

PMID- 29588595
TI  - The impact of a combined intervention program: an educational and clinical
      pharmacist's intervention to improve prescribing pattern in hospitalized
      geriatric patients at King Abdulaziz Medical City in Riyadh, Saudi Arabia.
AB  - Background: There is a difference between evidence-based guidelines for geriatric
      patients and clinical practice of physicians. Prescribing potentially
      inappropriate medications (PIMs) can be attributed to the fact that many
      physicians are not aware of PIMs usage. Aim: The aim of this study was to assess
      the effectiveness of a combined intervention program comprising an educational
      and clinical pharmacist intervention to reduce the incidence of PIMs among
      hospitalized geriatric patients. Methods: This was a prospective pre-test versus
      post-test design study. The screening tool of older persons' prescriptions, 2nd
      version, and 2015 American Geriatric Society Beers' criteria were used to assess
      the appropriateness of medications prescribed for geriatric inpatients. The study
      was carried out in the medical wards of the Department of Medicine at King
      Abdulaziz Medical City in Riyadh, Saudi Arabia. Results: Four hundred geriatric
      patients were enrolled in the study: 200 in a pre-intervention group (control)
      and 200 in the intervention group. After the combined intervention, the incidence
      rate of PIMs decreased significantly from 61% to 29.5% (p<0.001). Out of 317
      recommendations given by the clinical pharmacist, the physicians accepted a total
      of 196 (61.83%) recommendations. The most common PIMs to avoid regardless of
      diagnosis of geriatric patients before interventions were first-generation
      antihistamines (46%), sliding scale insulin (18.5%), antipsychotics (6.5%),
      benzodiazepines (9.5%), and antiarrhythmic drugs (15%). Conclusion: Using a
      combined intervention program that comprises an educational intervention of
      updated evidence-based guidelines and clinical pharmacist intervention would add
      a significant value to improve prescribing patterns in hospitalized geriatric
      patients.

PMID- 29588596
TI  - Patients with heart failure and their partners with chronic illness:
      interdependence in multiple dimensions of time.
AB  - Background: Informal caregivers play a vital role in supporting patients with
      heart failure (HF). However, when both the HF patient and their long-term partner
      suffer from chronic illness, they may equally suffer from diminished quality of
      life and poor health outcomes. With the focus on this specific couple group as a
      dimension of the HF health care team, we explored this neglected component of
      supportive care. Materials and methods: From a large-scale Canadian multisite
      study, we analyzed the interview data of 13 HF patient-partner couples (26
      participants). The sample consisted of patients with advanced HF and their long
      term, live-in partners who also suffer from chronic illness. Results: The
      analysis highlighted the profound enmeshment of the couples. The couples'
      interdependence was exemplified in the ways they synchronized their experience in
      shared dimensions of time and adapted their day-to-day routines to accommodate
      each other's changing health status. Particularly significant was when both
      individuals were too ill to perform caregiving tasks, which resulted in the
      couples being in a highly fragile state. Conclusion: We conclude that the
      salience of this couple group's oscillating health needs and their severe
      vulnerabilities need to be appreciated when designing and delivering HF team
      based care.

PMID- 29588597
TI  - Peripheral inflammation/immune indicators of chemosensitivity and prognosis in
      breast cancer patients treated with neoadjuvant chemotherapy.
AB  - Introduction: Neoadjuvant chemotherapy (NAC) has become a standard treatment for
      locally advanced breast cancer. The present study was designed to investigate the
      predictive value of different peripheral inflammation/immune biomarker responses
      to NAC and prognosis in breast cancer patients. Materials and methods: A total of
      180 breast cancer patients treated with NAC in the First Affiliated Hospital with
      Nanjing Medical University between January 2008 and March 2015 were enrolled in
      the study. The associations between inflammation/immune indicators and
      pathological complete response (pCR) were determined, and the prognostic value of
      inflammation/immune indicators was also evaluated. Results: In the univariate
      analysis, patients with a high pretreatment peripheral lymphocyte count
      (.2.06*109/L) showed a higher pCR rate than those with a low lymphocyte count
      (23.9% vs 10.4%, P=0.023). The pCR rate of patients with a neutrophil: lymphocyte
      ratio <=2.15 was significantly higher than that of patients with a high
      neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03). However, multivariate
      analysis revealed that only the high lymphocyte count was predictive for pCR
      (odds ratio: 4.375, 95% CI: 1.429-13.392, P=0.010). In the survival analysis,
      patients with a higher neutrophil count (.2.65*109/L) were confirmed to have a
      shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.028-18.174,
      P=0.046), and the high neutrophil count was significantly associated with
      lymphovascular invasion (P=0.037). Conclusion: We demonstrated that a high level
      of baseline peripheral lymphocyte count can be a predictor for high efficacy of
      NAC for breast cancer patients, and low baseline peripheral neutrophil count may
      contribute to the favorable disease-free survival.

PMID- 29588598
TI  - Measurement of serum PODXL concentration for detection of pancreatic cancer.
AB  - Background: The aim of this study was to investigate the use of podocalyxin
      (PODXL) and secretoglobin family 1D, member 2 (SCGB1D2) expressions in whole
      blood as diagnostic biomarkers to distinguish between patients with pancreatic
      cancer and control participants, in comparison with serum cancer antigen 19-9
      (CA19-9), which is the current clinical standard. Patients and methods: Flow
      cytometric analysis was performed to determine the expressions of PODXL and
      SCGB1D2 on the surface of cultured pancreatic cancer cells. Immunoblotting was
      performed to determine whether PODXL and SCGB1D2 were detectable in the media of
      cultured pancreatic cancer cells. A discovery-stage clinical study was performed
      in a cohort of 23 patients with pancreatic cancer and 51 control individuals
      without pancreatic disease who had been treated in the Department of
      Gastroenterology and Hepatology at Kochi Medical School Hospital from April 2014
      to January 2016. Serum PODXL and SCGB1D2 levels were measured by enzyme-linked
      immunosorbent assay (ELISA). Results: PODXL and SCGB1D2 accumulated in the
      protrusions of cultured pancreatic cancer cells, and they were detectable both on
      the cell surface and in the cultured media from these cells. The discovery-stage
      clinical study showed that the area under the receiver-operating characteristic
      curve (AUC) was 0.96 (95% confidence interval [CI] 0.91-1.000) for PODXL, 0.80
      (95% CI 0.67-0.94) for SCGB1D2, and 0.78 (95% CI 0.66-0.90) for CA19-9. The AUC
      for PODXL was thus significantly higher than that for CA19-9 (P = 0.006). The
      combination of SCGB1D2 with CA19-9 did not significantly increase the AUC (0.83;
      95% CI 0.70-0.96) compared with the AUC for either SCGB1D2 or CA19-9 alone (P =
      0.563). Conclusion: PODXL may be a novel, non-invasive diagnostic biomarker for
      the detection of pancreatic cancer.

PMID- 29588599
TI  - Modulation of human melanoma cell proliferation and apoptosis by hydatid cyst
      fluid of Echinococcus granulosus.
AB  - Objective: The objective of this paper was to assess the effects of hydatid cyst
      fluid (HCF) of Echinococcus granulosus on melanoma A375 cell proliferation and
      apoptosis. Methods: A375 cells were classified into five groups by in vitro
      culture: normal group, control group, 10% HCF group, 20% HCF group and 30% HCF
      group. Trypan blue staining method was employed to detect the toxicity of HCF.
      Effects of different concentrations of HCF on melanoma A375 cell proliferation at
      different time points were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Flow cytometry and propidium iodide (PI)
      staining were used to detect cell cycle, and Annexin-V/PI double staining method
      was used to determine A375 cell apoptotic rate. Western blotting was applied to
      detect the expression of phosphorylated extracellular regulated protein kinases,
      proliferating cell nuclear antigen (PCNA), cell-cycle-related proteins (cyclin A,
      cyclin B1, cyclin D1 and cyclin E) and apoptosis-related proteins (Bcl-2, Bax and
      caspase-3). Results: HCF with a high concentration was considered as atoxic to
      A375 cells. HCF promoted A375 cell proliferation, and the effects got stronger
      with an increase in concentrations but was retarded after reaching a certain
      range of concentrations. HCF increased phosphorylation level and expression of
      extracellular regulated protein kinase, as well as PCNA expression. HCF also
      promoted the transferring progression of A375 cells from the G0/G1 phase to the S
      phase to increase the cell number in S phase and increased the expression of
      cyclin A, cyclin D1 and cyclin E. HCF increased the expression of procaspase-3
      (the precursor of apoptosis-related protein caspase-3) and antiapoptotic protein
      Bcl-2, and decreased the expression of proapoptotic factor Bax, thereby
      inhibiting cell apoptosis. Conclusion: As a result, this study confirmed that HCF
      promotes proliferation and inhibits apoptosis of melanoma A375 cells.

PMID- 29588600
TI  - Identification of differentially expressed genes and signaling pathways in
      ovarian cancer by integrated bioinformatics analysis.
AB  - Background: The mortality rate associated with ovarian cancer ranks the highest
      among gynecological malignancies. However, the cause and underlying molecular
      events of ovarian cancer are not clear. Here, we applied integrated
      bioinformatics to identify key pathogenic genes involved in ovarian cancer and
      reveal potential molecular mechanisms. Results: The expression profiles of
      GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus
      (GEO) database, which contained 115 samples, including 85 cases of ovarian cancer
      samples and 30 cases of normal ovarian samples. The three microarray datasets
      were integrated to obtain differentially expressed genes (DEGs) and were deeply
      analyzed by bioinformatics methods. The gene ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by DAVID
      and KOBAS online analyses, respectively. The protein-protein interaction (PPI)
      networks of the DEGs were constructed from the STRING database. A total of 190
      DEGs were identified in the three GEO datasets, of which 99 genes were
      upregulated and 91 genes were downregulated. GO analysis showed that the
      biological functions of DEGs focused primarily on regulating cell proliferation,
      adhesion, and differentiation and intracellular signal cascades. The main
      cellular components include cell membranes, exosomes, the cytoskeleton, and the
      extracellular matrix. The molecular functions include growth factor activity,
      protein kinase regulation, DNA binding, and oxygen transport activity. KEGG
      pathway analysis showed that these DEGs were mainly involved in the Wnt signaling
      pathway, amino acid metabolism, and the tumor signaling pathway. The 17 most
      closely related genes among DEGs were identified from the PPI network.
      Conclusion: This study indicates that screening for DEGs and pathways in ovarian
      cancer using integrated bioinformatics analyses could help us understand the
      molecular mechanism underlying the development of ovarian cancer, be of clinical
      significance for the early diagnosis and prevention of ovarian cancer, and
      provide effective targets for the treatment of ovarian cancer.

PMID- 29588602
TI  - Upregulated long non-coding RNAs demonstrate promising efficacy for breast cancer
      detection: a meta-analysis.
AB  - Purpose: Focusing on the latest literature, dysregulated long non-coding RNAs
      (lncRNAs) have been extensively explored in breast cancer (BC) research. The
      purpose of this meta-analysis is to synthesize the evidence on the diagnostic
      performance of abnormally expressed lncRNAs for BC. Materials and methods:
      Relevant studies were searched in multiple electronic databases. The Quality
      Assessment of Diagnosis Accuracy Studies II criteria were applied to assess the
      quality of included studies. The bivariate meta-analysis model was applied to
      synthesize the diagnostic parameters using Stata 12.0 software. Publication bias
      was judged in terms of the Deek's funnel plot asymmetry test. Results: We
      included 10 eligible studies, which comprised 835 BC patients and 725 paired
      controls for this meta-analysis. The pooled sensitivity, specificity, diagnostic
      odds ratio, likelihood ratio positive, likelihood ratio negative, and area under
      the curve (AUC) of upregulated lncRNA expression signature in confirming BC were
      0.79 (95% CI: 0.70-0.85), 0.80 (95% CI: 0.73-0.85), 14.61 (95% CI: 10.91-19.55),
      3.90 (95% CI: 3.03-5.02), 0.27 (95% CI: 0.20-0.36), and 0.86, respectively.
      Stratified analyses yielded a sensitivity of 0.83 (95% CI: 0.80-0.86) for serum
      based analysis, which was higher than plasma-based analysis, whereas plasma-based
      analysis revealed a greater specificity of 0.88 (95% CI: 0.85-0.91). Moreover,
      lncRNA-homeotic genes (HOX) transcript antisense RNA showed a pooled specificity
      of 0.89 (95% CI: 0.84-0.93) and AUC of 0.86, which were superior to performances
      by lncRNA-metastasis-associated lung adenocarcinoma transcript-1 and -H19 in
      diagnosing BC. Notably, the analysis based on cancer subtypes demonstrated that
      lncRNA expression signature could distinguish triple-negative BC (lacks estrogen
      receptor, progesterone receptor, and human epidermal growth factor receptor 2
      expression) from non-triple-negative BC, with an AUC of 0.85. Conclusion:
      Upregulated lncRNAs reveal an immense potential as novel non-invasive
      biomarker(s) that could complement BC diagnosis.

PMID- 29588601
TI  - Midazolam activates caspase, MAPKs and endoplasmic reticulum stress pathways, and
      inhibits cell cycle and Akt pathway, to induce apoptosis in TM3 mouse Leydig
      progenitor cells.
AB  - Background: Midazolam (MDZ) has powerful hypnosis, amnesia, anti-anxiety and
      anticonvulsant effects. Studies have shown that prenatally developmental toxicity
      of diazepam can be observed in many organs/tissues. However, it remains elusive
      in male reproductive system. Materials and methods: TM3 mouse Leydig progenitor
      cell line was used to determine whether MDZ has any unfavorable effects. Results:
      Midazolam significantly decreased cell viability in dose- and time-dependent
      manners in TM3 cells. In flow cytometry analysis, midazolam significantly
      increased subG1 phase cell numbers, and annexin V/PI double staining assay
      further confirmed that MDZ induced apoptosis in TM3 cells. Moreover, MDZ
      significantly induced the expression of caspase-8 and -3 proteins and the
      phosphorylation of JNK, ERK1/2 and p38. Besides, MDZ didn't activate Akt pathway
      in TM3 cells. Furthermore, the expressions of p-EIF2alpha, ATF4, ATF3 and CHOP
      were induced by midazolam, suggesting that midazolam could induce apoptosis
      through endoplasmic reticulum (ER) stress in TM3 cells. Additionally, the
      expressions of cyclin A, cyclin B and CDK1 were inhibited by midazolam through
      the regulation of p53 in TM3 cells, indicating that midazolam could regulate cell
      cycle to induce apoptosis. Conclusion: Midazolam could activate caspase, MAPKs
      and ER stress pathways and impede Akt pathway and cell cycle to induce apoptosis
      in TM3 mouse Leydig progenitor cells.

PMID- 29588603
TI  - STK39 blockage by RNA interference inhibits the proliferation and induces the
      apoptosis of renal cell carcinoma.
AB  - Aim: Renal cell carcinoma (RCC), the most frequent type of primary renal
      malignancies, has a high mortality rate. Serine/threonine kinase 39 (STK39) is
      associated with various human diseases, including cancers. The current study
      aimed to investigate the functions of STK39 in RCC. Materials and methods: STK39
      expression levels in RCC and paired normal renal tissue samples were detected by
      real-time polymerase chain reaction and Western blotting analyses. The biological
      functions of STK39 were explored in two RCC cell lines with STK39 silence.
      Results: STK39 expression was significantly increased in RCC tissues than in
      normal renal tissues. Suppression of STK39 expression in ACHN and 786-0 cells
      significantly suppressed cell proliferation and induced cell apoptosis.
      Consistently, the expression of PCNA and Bcl-2 was remarkably increased, while
      the expression of Bax was significantly in STK39 knockdown cells compared to
      control cells. Furthermore, gene set enrichment analysis identified STK39 as an
      important regulator of p53 and p38 signaling pathways. STK39 knockdown increased
      p53 expression and inhibited p38 phosphorylation. Moreover, ectopic expression of
      STK39 in ACHN cells resulted in a reduced p53 expression and increased c-Myc and
      p-p38 expression. Such effects were suppressed by p38 inhibitor (SB203580).
      Conclusion: STK39 may exert its oncogenic function in RCC through p38 signaling.
      Our data suggest that STK39 may represent a potential therapeutic target against
      RCC.

PMID- 29588604
TI  - Primary mucinous carcinoma of thyroid gland with prominent signet-ring-cell
      differentiation: a case report and review of the literature.
AB  - Purpose: This study reports a case of primary mucinous carcinoma of the thyroid
      gland with signet-ring-cell differentiation, and reviews the literature to
      evaluate its real incidence and the prognosis of these patients. Patients and
      methods: A 74-year-old Chinese woman, presenting with a mass in the right lobe of
      thyroid gland, came to the hospital. Computed tomography revealed a mass in the
      right lobe of the thyroid gland, accompanied with right neck lymphadenectasis and
      airway deviation caused by tumor compression. Thyroid imaging suggested a thyroid
      malignant tumor and suspicious lymph node metastasis. Histologically, the tumor
      was characterized by the tumor cells arranged in small nests or trabeculae with
      an abundant extracellular mucoid matrix. The tumor cells formed diffuse invasion
      among thyroid follicles. In the peripheral regions, prominent signet-ring-cells
      formed a sheet-like structure and extended into the extrathyroidal fat tissue.
      The tumor cells were diffusely positive for thyroid transcription factor-1 (TTF
      1) and PAX8, while they were focally positive for pan-cytokeratin (AE1/AE3) and
      weakly expressed thyroglobulin. Results: Based on the histological features and
      immunohistochemical profile, a diagnosis of primary mucinous carcinoma of the
      thyroid gland with signet-ring-cell differentiation was rendered. Conclusion:
      Using a panel of immunohistochemical markers may be helpful for differential
      diagnosis and for determining whether the tumor is primary or not.

PMID- 29588605
TI  - A systematic review and meta-analysis on the use of prophylactic topical
      antibiotics for the prevention of uncomplicated wound infections.
AB  - Background: The prescription of topical antibiotics for the prevention of
      infections in uncomplicated wounds is common. However, the efficacy is not well
      reported. Therefore, the objective of the study was to conduct a systematic
      review and meta-analysis of the available evidence on prevention of uncomplicated
      wound infections by prophylactic topical antibiotics. Materials and methods: The
      search included Pubmed, Google Scholar, SCOPUS, Embase, Cochrane,
      ClinicalTrials.gov, International Clinical Trials Registry Platform, National
      Technical Information Service, and the National Guidelines Clearinghouse.
      Results: We identified eight randomized controlled trials and four quasi
      randomized trials that met the criteria for the systematic review. Of these
      trials, 11 studies were pooled for meta-analysis to compare the effects of
      topical antibiotics versus placebo and 4 studies were pooled for comparison of
      effects of topical antibiotics versus topical antiseptics on uncomplicated
      wounds. Fewer wound infections occurred in the topical antibiotic arms compared
      to placebo (pooled risk ratio: 0.57 [95% CI: 0.37 to 0.86]; p=0.01 and pooled
      risk difference: -3.1% [95% CI: -5.8% to -0.34%]; p=0.03). Compared to
      antiseptics, topical antibiotics demonstrated statistically significant relative
      risk reduction (pooled risk ratio: 0.56 [95% CI: 0.23 to 0.91]; p=0.02), while
      there was no significant absolute risk reduction (pooled risk difference: -3.7%
      [95% CI: -7.9% to +0.6%]; p=0.09). Conclusion: Topical antibiotics are effective
      in reducing wound infections after surgical procedures, but the absolute benefit
      is small. Given the global emergence of antimicrobial resistance, judicious use
      of antibiotics is encouraged and use of antiseptics should be considered as a
      reasonable alternative to topical antibiotics.

PMID- 29588606
TI  - Cost utility, budget impact, and scenario analysis of racecadotril in addition to
      oral rehydration for acute diarrhea in children in Malaysia.
AB  - Objective: To perform cost utility (CU) and budget impact (BI) analyses augmented
      by scenario analyses of critical model structure components to evaluate
      racecadotril as adjuvant to oral rehydration solution (ORS) for children under 5
      years with acute diarrhea in Malaysia. Methods: A CU model was adapted to
      evaluate racecadotril plus ORS vs ORS alone for acute diarrhea in children
      younger than 5 years from a Malaysian public payer's perspective. A bespoke BI
      analysis was undertaken in addition to detailed scenario analyses with respect to
      critical model structure components. Results: According to the CU model, the
      intervention is less costly and more effective than comparator for the base case
      with a dominant incremental cost-effectiveness ratio of -RM 1,272,833/quality
      adjusted life year (USD -312,726/quality-adjusted life year) in favor of the
      intervention. According to the BI analysis (assuming an increase of 5% market
      share per year for racecadotril+ORS for 5 years), the total cumulative
      incremental percentage reduction in health care expenditure for diarrhea in
      children is 0.136578%, resulting in a total potential cumulative cost savings of 
      RM 73,193,603 (USD -17,983,595) over a 5-year period. Results hold true across a
      range of plausible scenarios focused on critical model components. Conclusion:
      Adjuvant racecadotril vs ORS alone is potentially cost-effective from a Malaysian
      public payer perspective subject to the assumptions and limitations of the model.
      BI analysis shows that this translates into potential cost savings for the
      Malaysian public health care system. Results hold true at evidence-based base
      case values and over a range of alternate scenarios.

PMID- 29588607
TI  - Cost analysis of a growth guidance system compared with traditional and
      magnetically controlled growing rods for early-onset scoliosis: a US-based
      integrated health care delivery system perspective.
AB  - Purpose: Treating early-onset scoliosis (EOS) with traditional growing rods (TGR)
      is effective but requires periodic surgical lengthening, risking complications.
      Alternatives include magnetically controlled growing rods (MCGR) that lengthen
      noninvasively and the growth guidance system (GGS), which obviate the need for
      active, distractive lengthenings. Previous studies have reported promising
      clinical effectiveness for GGS; however the direct medical costs of GGS compared
      to TGR and MCGR have not yet been explored. Methods: To estimate the cost of GGS
      compared with MCGR and TGR for EOS an economic model was developed from the
      perspective of a US integrated health care delivery system. Using dual-rod
      constructs, the model estimated the cumulative costs associated with initial
      implantation, rod lengthenings (TGR, MCGR), revisions due to device failure,
      surgical-site infections, device exchange, and final spinal fusion over a 6-year
      episode of care. Model parameters were from peer-reviewed, published literature.
      Medicare payments were used as a proxy for provider costs. Costs (2016 US$) were
      discounted 3% annually. Results: Over a 6-year episode of care, GGS was
      associated with fewer invasive surgeries per patient than TGR (GGS: 3.4; TGR:
      14.4) and lower cumulative costs than MCGR and TGR, saving $25,226 vs TGR.
      Sensitivity analyses showed that results were sensitive to changes in construct
      costs, rod breakage rates, months between lengthenings, and TGR lengthening
      setting of care. Conclusion: Within the model, GGS resulted in fewer invasive
      surgeries and deep surgical site infections than TGR, and lower cumulative costs
      per patient than both MCGR and TGR, over a 6-year episode of care. The analysis
      did not account for family disruption, pain, psychological distress, or
      compromised health-related quality of life associated with invasive TGR
      lengthenings, nor for potential patient anxiety surrounding the frequent MCGR
      lengthenings. Further analyses focusing strictly on current generation
      technologies should be considered for future research.

PMID- 29588608
TI  - The relationship between mitotic rate and depth of invasion in biopsies of
      malignant melanoma.
AB  - Background: Malignant melanoma of the skin is a potentially lethal neoplasm that
      generally originates from atypical melanocytes in the dermal-epidermal junction.
      When the neoplasm penetrates into the dermis, several variables can affect the
      extent of its spread, among which depth of invasion has the most important
      prognostic value. Mitotic rate is another prognostic factor that reflects the
      biological behavior of the neoplasm. Objective: This study was designed to
      evaluate the probable relationship between the depth of invasion of malignant
      melanoma and its mitotic rate. Materials and methods: This study was performed on
      50 excisional biopsy specimens that had received the diagnosis of malignant
      melanoma histopathologically. Tumor characteristics including Breslow thickness,
      Clark level, T-stage, and tumor mitotic rate were recorded. Results: We observed
      that at higher Clark levels and higher T-stages, and the mean mitotic rate was
      significantly increased. Moreover, there was a positive and significant
      correlation between Breslow thickness and mitotic rate. We demonstrated that one
      unit increase in mitotic rate was correlated with 0.8 mm increase in Breslow
      thickness of the tumor. Conclusion: In malignant melanoma, mitotic activity may
      probably indicate the depth of tumor invasion. Therefore, in incisional biopsies
      where depth of invasion cannot be accurately determined, the mitotic activity may
      be used to estimate Breslow thickness, which is necessary for planning surgical
      management.

PMID- 29588610
TI  - Unmet service needs evaluated by case managers among disabled patients on
      hemodialysis in Japan.
AB  - Background: This study aimed to investigate the levels of unmet needs for home
      and community-based services (HCBS) evaluated by case managers (CMs) among
      disabled patients on hemodialysis (DPHD) and to examine factors related to unmet
      needs. Unmet needs for HCBS were defined as situations in which patients do not
      use or underuse HCBS despite needing them. Candidates for the factors relating to
      unmet needs for HCBS included three dimensions: predisposing, enabling, and need
      factors. Methods: Self-administrated questionnaires were collected from 391 CMs
      of DPHD certified with long-term care insurance. These were introduced by the
      dialysis facilities that a member of the Japanese Association of Dialysis
      Physicians belonged to. CMs were asked questions about their management of each
      individual case. HCBS included home help, visiting nursing, daycare, and short
      stay. Results: The prevalence of unmet needs for each HCBS ranged from 32% for
      home help to 48% for short stay. Barriers to service usage in the patients were
      associated with unmet needs for all four services. The patients with more severe
      cognitive malfunction were more likely to have unmet needs for visiting nursing
      and short stay. Heavier burden with caregiving was associated with more
      likelihood of unmet needs for home help and short stay. Conclusion: CMs need to
      monitor unmet needs after coordinating HCBS for DPHD and need to encourage HBCS
      use among patients with impaired cognitive function and caregivers with heavier
      caregiving burdens.

PMID- 29588609
TI  - Postoperative pancreatic fistula: a review of traditional and emerging concepts.
AB  - Postoperative pancreatic fistula (POPF) remains the major cause of morbidity
      after pancreatic resection, affecting up to 41% of cases. With the recent
      development of a consensus definition of POPF, there has been a large number of
      reports examining various risk factors, prediction models, and mitigation
      strategies for this costly complication. Despite these strategies, the rates of
      POPF have not significantly diminished. Here, we review the literature and
      evidence regarding both traditional and emerging concepts in POPF prediction,
      prevention, and management. In particular, we review the evidence for the
      association between postoperative pancreatitis and POPF, and present a novel
      proposed mechanism for the development of POPF.

PMID- 29588611
TI  - The utility of pharmacogenetic testing to support the treatment of bipolar
      disorder.
AB  - Background: Bipolar disorder (BD) is a frequent cause of disability, health care
      costs, and risk of suicide. Pharmacogenetic tests (PGTs) could help clinicians to
      identify those patients predisposed to the occurrence of adverse events (AEs)
      improving the understanding of the correlation between genetic variants and drug
      response. Materials and methods: The study evaluated 30 patients affected by BD
      type I or II (according to Diagnostic and Statistical Manual of Mental Disorders,
      version 5) who underwent the PGT Neurofarmagen(r) (AB-BIOTICS SA, Barcelona,
      Spain) between March 2016 and March 2017. The primary aim of this study was to
      identify if the treatment prescribed by the psychiatrists was consistent with the
      treatment suggested by the PGT at T0 (corresponding to the test report
      communication). As a secondary aim, we wanted to assess if clinicians had changed
      the treatment (in case of discordance) at T1 (3-month follow-up visit) according
      to the results of the PGT. Results: At T0, only 4 patients (13%) had an optimal
      therapy in line with the PGT suggestions. At 3-month follow-up, 13 patients (40%)
      had received a change of therapy consistent to the test, showing a significant
      statistical improvement in the Clinical Global Impression item Severity (CGI-S)
      score over time compared to those not having changes consistent with the test.
      Regarding AEs, at baseline 9 out of 10 (90%) of the patients who received a
      therapy modification according to the test presented AEs, and a significant
      within-group reduction was observed after 3 months (p = 0.031). Conclusion:
      Despite the small sample size, the study shows promising data about the
      usefulness of PGT to support clinicians in reaching a more effective and
      tolerated treatment in the routine approach of BD.

PMID- 29588612
TI  - Radiation-induced neuropathic pain successfully treated with systemic lidocaine
      administration.
AB  - Radiation-induced neuropathic pain is a rare but devastating complication
      following cancer treatment. It is often progressive, refractory to conservative
      treatment, and sometimes irreversible. The exact mechanism of radiation-induced
      neuropathic pain is unknown, but it is associated with perineural fibrosis,
      atrophy, and ischemia. Systemic administration of local anesthetics is known to
      be effective for various acute and chronic painful diseases, such as neuropathic
      pain, as well as inflammatory and nociceptive pains. We report a patient with
      generalized radiation-induced neuropathic pain successfully treated with systemic
      lidocaine administration.

PMID- 29588613
TI  - Buprenorphine and pain treatment in pediatric patients: an update.
AB  - Introduction: The usual management of moderate to severe pain is based on the use
      of opioids. Buprenorphine (BPN) is an opioid with an analgesic potency 50 times
      greater than that of morphine. It is widely used in various pain models and has
      demonstrated efficacy and safety in adult patients; however, there are
      insufficient clinical trials in pediatric populations. Purpose: The aim of this
      study was to perform an updated meta-analysis on the implementation of BPN in the
      treatment of pain in the pediatric population. Methods: A bibliographic search
      was carried out in different biomedical databases to identify scientific papers
      and clinical trials with evidence of BPN use in children and adolescents.
      Results: A total of 89 articles were found, of which 66 were selected. Analysis
      of these items revealed additional sources, and the final review included a total
      of 112 publications. Conclusion: Few studies were found regarding the efficacy
      and safety of BPN use in children. In recent years, the use of this drug in the
      pediatric population has become widespread, so it is imperative to perform
      clinical trials and pharmacological and pharmacovigilance studies, which will
      allow researchers to develop dosage schemes based on the evidence and minimize
      the risk of adverse effects.

PMID- 29588614
TI  - Practice and bias in intraoperative pain management: results of a cross-sectional
      patient study and a survey of anesthesiologists.
AB  - Background: Perioperative pain carries a considerable risk of becoming
      persistent; hence aggressive preventive approaches are advocated. Persistently
      high prevalence of postoperative pain, however, suggests anesthesiologists
      underuse these strategies. A prospective cross-sectional study of patients in the
      postanesthetic care unit (PACU) and a survey of anesthesiologists were thus
      conducted to evaluate practice and uncover bias in intraoperative pain
      management. Methods: Notes of PACU patients were reviewed and information
      regarding surgical context, comorbidities, and analgesic administration was
      retrieved. Variables were analyzed for their predictive properties on pain and
      intraoperative analgesic management. Furthermore, clinical dose-effect estimates
      for intraoperative morphine were determined. Finally, anesthesiologists completed
      a questionnaire comprising statements regarding pain relating to surgical context
      and morphine administration. Results: Data of 200 patients and 55
      anesthesiologists were analyzed. Prevalence of pain in PACU was 28% and was
      predicted by local anesthetic (LA) and low-dose morphine administration.
      Additionally, when LA was used, little coanalgesics were employed. These results
      suggest a restrained approach by anesthesiologists toward intraoperative pain
      management. It is supported by their reluctance to administer more than 10 mg
      morphine, despite these individuals regarding this practice as insufficient. The
      hesitancy toward morphine also transpired in the dose-effect estimates with the
      average applied dose operating on an ED63 instead of an ED95 level. Conclusion:
      This study confirmed a high prevalence of pain in PACU. It also indicated
      conservative intraoperative analgesic administration by anesthesiologists. The
      modest morphine usage and overreliance on LA application, which are not supported
      by published evidence, additionally suggest bias in current intraoperative pain
      management.

PMID- 29588616
TI  - Optimal management of orthodontic pain.
AB  - Pain is an undesirable side effect of orthodontic tooth movement, which causes
      many patients to give up orthodontic treatment or avoid it altogether. The aim of
      this study was to investigate, through an analysis of the scientific literature,
      the best method for managing orthodontic pain. The methodological aspects
      involved careful definition of keywords and diligent search in databases of
      scientific articles published in the English language, without any restriction of
      publication date. We recovered 1281 articles. After the filtering and
      classification of these articles, 56 randomized clinical trials were selected. Of
      these, 19 evaluated the effects of different types of drugs for the control of
      orthodontic pain, 16 evaluated the effects of low-level laser therapy on
      orthodontic pain, and 21 evaluated other methods of pain control. Drugs reported
      as effective in orthodontic pain control included ibuprofen, paracetamol,
      naproxen sodium, aspirin, etoricoxib, meloxicam, piroxicam, and tenoxicam. Most
      studies report favorable outcomes in terms of alleviation of orthodontic pain
      with the use of low-level laser therapy. Nevertheless, we noticed that there is
      no consensus, both for the drug and for laser therapy, on the doses and clinical
      protocols most appropriate for orthodontic pain management. Alternative methods
      for orthodontic pain control can also broaden the clinician's range of options in
      the search for better patient care.

PMID- 29588617
TI  - Intensity of treatment in Swiss cancer patients at the end-of-life.
AB  - Purpose: Current evidence on the care-delivering process and the intensity of
      treatment at the end-of-life of cancer patients is limited and remains unclear.
      Our objective was to examine the care-delivering processes in health care during
      the last months of life with real-life data of Swiss cancer patients. Patients
      and methods: The study population consisted of adult decedents in 2014 who were
      insured at Helsana Group. Data on the final cause of death were provided
      additionally by the Swiss Federal Statistical Office. Of the 10,275 decedents,
      2,710 (26.4%) died of cancer. Intensity of treatment and health care utilization
      (including transitions) at their end-of-life were examined. Intensity measures
      included the following: last dose of chemotherapy within 14 days of death, a new
      chemotherapy regimen starting <30 days before death, more than one hospital
      admission or spending >14 days in hospital in the last month, death in an acute
      care hospital, more than one emergency visit and >=1 intensive care unit
      admission in the last month of life. Results: In the last 6 months of life, 89.5%
      of cancer patients had >=1 transition, with 87.2% being hospitalized. Within 30
      days before death, 64.2% of the decedents had >=1 intensive treatment, whereby
      8.9% started a new chemotherapy. In the multinomial logistic regression model,
      older age, higher density of nursing home beds and home care nurses were
      associated with a decrease, while living in the Italian- or French-speaking part
      of Switzerland was associated with an increase in intensive care. Conclusion:
      Swiss cancer patients insured by Helsana Group experience a considerable number
      of transitions and intensive treatments at the end-of-life, whereby treatment
      intensity declines with increasing age. Among others, increased home care nursing
      might be helpful to reduce unwarranted treatments and transitions, therefore
      leading to better care at the end-of-life.

PMID- 29588618
TI  - Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell
      carcinoma.
AB  - Background: Due to the high-quality immunogenicity of tumor-derived
      autophagosomes (DRibbles), we aimed to explore the antitumor ability and
      mechanism of DRibble-loaded dendritic cells (DRibble-DCs). Materials and methods:
      DRibbles extracted from the oral squamous cell carcinoma cell line SCC7 express
      specific LC3-II and ubiquitination marker. Immunization of mice with the DRibble
      DCs vaccine led to the proliferation and differentiation of CD3+CD4+IFN-gamma+
      and CD3+CD8+IFN-gamma+ T cells. The expression of proteins in endoplasmic
      reticulum stress (ERS) pathways was determined by Western blotting. Additionally,
      the functional properties of the DRibble-DCs were examined in mice, and
      regulatory T cells were measured by flow cytometry. Results: Excellent
      biocompatibility was observed in vitro when DCs were loaded with DRibbles. T
      cells of lymph nodes and spleens from mice immunized with DRibble-DCs had
      cytotoxic effects on SCC7 cells. DCs homeostasis and ERS-related proteins were
      affected by DRibbles. Moreover, the DRibble-DCs vaccine achieved significantly
      better antitumor efficacy than DRibbles and tumor cell lysate-loaded DCs.
      Conclusion: The results validated the antitumor immune responses to the DRibble
      DCs vaccine in vivo and in vitro. The ERS pathway can be affected by DRibbles.

PMID- 29588615
TI  - Management of pain in patients with temporomandibular disorder (TMD): challenges
      and solutions.
AB  - Thanks to advances in neuroscience, biopsychosocial models for diagnostics and
      treatment (including physical, psychological, and pharmacological therapies)
      currently have more clinical support and scientific growth. At present, a
      conservative treatment approach prevails over surgery, given it is less
      aggressive and usually results in satisfactory clinical outcomes in mild-moderate
      temporomandibular disorder (TMD). The aim of this review is to evaluate the
      recent evidence, identify challenges, and propose solutions from a clinical point
      of view for patients with craniofacial pain and TMD. The treatment we propose is
      structured in a multi-modal approach based on a biobehavioral approach that
      includes medical, physiotherapeutic, psychological, and dental treatments. We
      also propose a new biobehavioral model regarding pain perception and motor
      behavior for the diagnosis and treatment of patients with painful TMD.

PMID- 29588619
TI  - Primary clear cell carcinoma of the thymus and literature comparison of features.
AB  - Clear cell carcinoma arising from the thymus is considered exceedingly rare. It
      shows aggressive clinical behavior and demonstrates frequent local recurrences as
      well as widespread metastasis. The detailed clinical data of one patient with
      thymic clear cell carcinoma were compiled, and a review of relevant reported
      studies was performed. We summarized the clinical characteristics, pathological
      diagnosis of the patient and other reported cases. The analysis showed that older
      male patients were more likely to suffer, and the manifestations included chest
      pain and dyspnea. Some patients are asymptomatic, with the tumor being discovered
      during physical examination. Histologically, thymic clear cell carcinoma is
      composed of lobulated structures arranged in hyperchromatic fibrous stroma; the
      tumor cells are uniform with obvious nucleoli and clear cytoplasm. To establish
      the correct diagnosis, consideration and exclusion of metastasis and other
      original tumors in the differential diagnosis by immunohistochemistry, clinical
      and radiologic correlation is important.

PMID- 29588620
TI  - In-room ultrasound fusion combined with fully compatible 3D-printed holding arm -
      rethinking interventional MRI.
AB  - There is no real need to discuss the potential advantages - mainly the excellent
      soft tissue contrast, nonionizing radiation, flow, and molecular information - of
      magnetic resonance imaging (MRI) as an intraoperative diagnosis and therapy
      system particularly for neurological applications and oncological therapies.
      Difficult patient access in conventional horizontal-field superconductive
      magnets, very high investment and operational expenses, and the need for special
      nonferromagnetic therapy tools have however prevented the widespread use of MRI
      as imaging and guidance tool for therapy purposes. The interventional use of MRI
      systems follows for the last 20+ years the strategy to use standard diagnostic
      systems and add more or less complicated and expensive components (eg, MRI
      compatible robotic systems, specially shielded in-room monitors, dedicated tools
      and devices made from low-susceptibility materials, etc) to overcome the
      difficulties in the therapy process. We are proposing to rethink that approach
      using an in-room portable ultrasound (US) system that can be safely operated till
      1 m away from the opening of a 3T imaging system. The live US images can be
      tracked using an optical inside-out approach adding a camera to the US probe in
      combination with optical reference markers to allow direct fusion with the MRI
      images inside the MRI suite. This leads to a comfortable US-guided intervention
      and excellent patient access directly on the MRI patient bed. This was combined
      with an entirely mechanical MRI-compatible 7 degrees of freedom holding arm
      concept, which shows that this test environment is a different way to create a
      cost-efficient and effective setup that combines the advantages of MRI and US by
      largely avoiding the drawbacks of current interventional MRI concepts.

PMID- 29588621
TI  - Investigating the effects of cervical collar design and fit on the biomechanical
      and biomarker reaction at the skin.
AB  - Background: Research has shown that up to 33% of pressure ulcers (PUs) acquired
      in hospitals result from the application of a medical device. Cervical collars (C
      collars) have been implicated in causing PUs, due to the mechanical force they
      apply to the skin. In order to improve our understanding of collar-related PUs,
      the present study aimed to assess the biomechanical, biochemical, and
      microclimate effects of C-collar design and fitting tension. Methods: A cohort of
      15 healthy volunteers was fit with two different C-collars according to the
      manufacturer guidelines. Two further collar tensions were also defined as loose
      and tight for each device. Each collar condition was applied for 15 minutes, with
      a 10 minute refractory period. Measurements at the device-skin interface included
      interface pressures, inflammatory biomarkers, microclimate, range of cervical
      motion, and comfort scores. Results: The interface pressures at each tissue site
      increased monotonically with greater collar tension (p<0.01), irrespective of
      collar design. Biomarker analysis revealed that inflammatory cytokines (IL-1a)
      were elevated during collar application, with the highest increase during the
      tight fit condition, representing over a fourfold increase from unloaded
      conditions. Regardless of collar tension or type, there was an increase in
      temperature 1.5 degrees C +/-0.8 degrees C compared to baseline values. Range of
      motion significantly decreased with greater strap tension (p<0.05), with an
      associated increase in discomfort. Conclusion: The present findings revealed that
      increasing C-collar tensions caused elevated contact pressures at the device-skin
      interface, with a corresponding inflammatory response at the skin. These peak
      contact pressures were highest at the occiput, corresponding with reported PU
      locations. Devices should be designed to uniformly distribute pressures, and
      appropriate guidance is needed for their application.

PMID- 29588622
TI  - Physical activity after total joint arthroplasty: a narrative review.
AB  - Background: Total joint arthroplasty (TJA) is a common procedure to treat
      individuals with hip and knee osteoarthritis. While TJAs are successful in
      decreasing pain and improving quality of life, it is unclear whether individuals
      who undergo TJA become more physically active after surgery. It is possible that
      TJA, by itself, is not sufficient to affect the behavior of patients toward
      physical activity (PA) participation. To increase PA participation, individuals
      with TJA may need to be exposed to exercise/behavioral interventions specifically
      aimed to promote PA (ie, in addition to the surgery). Objectives: This narrative
      review aimed to assess the evidence on 1) whether TJAs change PA participation
      from pre- to postsurgery and 2) whether exercise/behavioral interventions
      delivered before or after TJA help to promote PA in these patients. Results: For
      aim 1, the studies that assessed PA from pre- to post-TJA reported that PA does
      not change in the first 3 months postsurgery. The results of follow-ups longer
      than 3 months but shorter than 12 months are contradictory, and the results of
      follow-ups longer than 12 months provide weak evidence of increased PA.
      Assessment of changes in PA due to TJA is challenged by the wide variability in
      demographics, methods used to assess PA, and different pathways of care used
      across studies. The results for aim 2 were limited by a scarcity of studies that
      used exercise/behavioral interventions to promote PA. Conclusion: TJA relieves
      joint pain and offers a unique opportunity for patients to become more physically
      active. However, the current evidence is limited and unable to offer definitive
      results of whether TJA is effective to change PA from pre- to postsurgery. Future
      large studies in representative samples of patients with TJA are needed to
      adequately answer this question.

PMID- 29588623
TI  - National Institutes of Health Toolbox Emotion Battery for English- and Spanish
      speaking adults: normative data and factor-based summary scores.
AB  - Background: The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB)
      is a "common currency", computerized assessment developed to measure the full
      spectrum of emotional health. Though comprehensive, the NIHTB-EB's 17 scales may
      be unwieldy for users aiming to capture more global indices of emotional
      functioning. Methods: NIHTB-EB was administered to 1,036 English-speaking and 408
      Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined
      the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and
      developed factor analysis-based summary scores. Census-weighted norms were
      presented for English speakers, and sample-weighted norms were presented for
      Spanish speakers. Results: Exploratory factor analysis for both English- and
      Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative
      affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory
      factor analysis supported similar factor structures for English- and Spanish
      speaking cohorts. Model fit indices fell within the acceptable/good range, and
      our final solution was optimal compared to other solutions. Conclusion: Summary
      scores based upon the normative samples appear to be psychometrically supported
      and should be applied to clinical samples to further validate the factor
      structures and investigate rates of problematic emotions in medical and
      psychiatric populations.

PMID- 29588624
TI  - Stereotactic body radiation therapy (SBRT) in the management of non-small-cell
      lung cancer: Clinical impact and patient perspectives.
AB  - Stereotactic body radiation therapy (SBRT) has emerged as a new technology in
      radiotherapy delivery, allowing for potentially curative treatment in many
      patients previously felt not to be candidates for radical surgical resection of
      stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated
      very high local control rates using SBRT, and more recent data have suggested
      overall survival may approach that of surgery in operable patients. However, SBRT
      is not without unique toxicities, and the balance of toxicity, and effect on
      patient-reported quality of life need to be considered with respect to oncologic
      outcomes. We therefore aim to review SBRT in the context of important patient
      related factors, including quality of life in several domains (and in comparison
      to other therapies such as conventional radiation, surgery, or no treatment). We
      will also describe scenarios in which SBRT may be reasonably offered (i.e.
      elderly patients and those with severe COPD), and where it may need to be
      approached with some caution due to increased risks of toxicity (i.e. tumor
      location, patients with interstitial lung disease). In total, we hope to
      characterize the physical, emotional, and functional consequences of SBRT, in
      relation to other management strategies, in order to aid the clinician in
      deciding whether SBRT is the optimal treatment choice for each patient with early
      stage NSCLC.

PMID- 29588625
TI  - Duchenne and Becker muscular dystrophy in adolescents: current perspectives.
AB  - Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are life
      limiting and progressive neuromuscular conditions with significant comorbidities,
      many of which manifest during adolescence. BMD is a milder presentation of the
      condition and much less prevalent than DMD, making it less represented in the
      literature, or more severely affected individuals with BMD may be subsumed into
      the DMD population using clinical cutoffs. Numerous consensus documents have been
      published on the clinical management of DMD, the most recent of which was
      released in 2010. The advent of these clinical management consensus papers,
      particularly respiratory care, has significantly increased the life span for
      these individuals, and the adolescent years are now a point of transition into
      adult lives, rather than a period of end of life. This review outlines the
      literature on DMD and BMD during adolescence, focusing on clinical presentation
      during adolescence, impact of living with a chronic illness on adolescents, and
      the effect that adolescents have on their chronic illness. In addition, we
      describe the role that palliative-care specialists could have in improving
      outcomes for these individuals. The increasing proportion of individuals with DMD
      and BMD living into adulthood underscores the need for more research into
      interventions and intracacies of adolescence that can improve the social aspects
      of their lives.

PMID- 29588626
TI  - Epistructured catechins, EGCG and EC facilitate apoptosis induction through
      targeting de novo lipogenesis pathway in HepG2 cells.
AB  - Background: Abnormally high expression of the mammalian de novo lipogenesis (DNL)
      pathway in various cancer cells promotes cell over-proliferation and resistance
      to apoptosis. Inhibition of key enzymes in the DNL pathway, namely, ATP citrate
      lyase, acetyl-CoA carboxylase, and fatty acid synthase (FASN) can increase
      apoptosis without cytotoxicity to non-cancerous cells, leading to the search for
      and presentation of novel selective and powerful targets for cancer therapy.
      Previous studies reported that epistructured catechins, epigallocatechin gallate
      (EGCG) and epicatechin (EC) exhibit different mechanisms regarding a strong
      inducer of apoptosis in various cancer cell lines. Thus, the current study
      investigated the growth inhibitory effect of EGCG and EC, on the enzyme
      expression and activity of the DNL pathway, which leads to the prominent activity
      of carnitine palmitoyl transferase-1 (CPT-1) mediating apoptosis in HepG2 cells.
      Methods: The cytotoxicity on HepG2 cells of EGCG and EC was determined by MTT
      assay. Cell death caused by apoptosis, the dissipation of mitochondrial membrane
      potential (MMP), and cell cycle arrest were then detected by flow cytometry. We
      further investigated the decrease of fatty acid levels associated with DNL
      retardation, followed by evaluation of DNL protein expression. Then, the negative
      inhibitory effect of depleted fatty acid synthesis on malonyl-CoA synthesis
      followed by regulating of CPT-1 activity was investigated. Thereafter, we
      inspected the enhanced reactive oxygen species (ROS) generation, which is
      recognized as one of the causes of apoptosis in HepG2 cells. Results: We found
      that EGCG and EC decreased cancer cell viability by increasing apoptosis as well
      as causing cell cycle arrest in HepG2 cells. Apoptosis was associated with MMP
      dissipation. Herein, EGCG and EC inhibited the expression of FASN enzymes
      contributing to decreasing fatty acid levels. Notably, this decrease consequently
      showed a suppressing effect on the CPT-1 activity. We suggest that epistructured
      catechin-induced apoptosis targets CPT-1 activity suppression mediated through
      diminishing the DNL pathway in HepG2 cells. In addition, increased ROS production
      was found after treatment with EGCG and EC, indicating oxidative stress mechanism
      induced apoptosis. The strong apoptotic effect of EGCG and EC was specifically
      absent in primary human hepatocytes. Conclusion: Our supportive evidence confirms
      potential alternative cancer treatments by EGCG and EC that selectively target
      the DNL pathway.

PMID- 29588627
TI  - Zymosan attenuates melanoma growth progression, increases splenocyte
      proliferation and induces TLR-2/4 and TNF-alpha expression in mice.
AB  - Background: Melanoma is one of the most common types of skin malignancies. Since
      current therapies are suboptimal, considerable interest has focused on novel
      natural-based treatments. Toll-like receptors (TLRs) play an important role in
      evoking innate immunity against cancer cells. Zymosan, a known TLR-2 agonist, is
      a glucan derived from yeast cell walls with promising immunomodulatory effects.
      The aim of this study was to evaluate whether Saccharomyces cerevisiae-derived
      zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4
      expression in peritoneal macrophages and serum TNF-alpha level. Methods: Male
      C57BL/6 mice were divided into four groups: i) zymosan-treated (Z), ii) Melanoma
      bearing mice (M), iii) Melanoma-bearing mice treated with zymosan (ZM) and iv) a
      healthy control group (negative control). 15 days after melanoma induction, mice
      were injected i.p. with zymosan (10 MUg) daily for 4 consecutive days. Mice were
      CO2-euthanized and serum TNF-alpha level, TLR-2 and TLR-4 expression in
      peritoneal macrophages and tumor growth measured. Splenocytes were treated ex
      vivo with zymosan to determine viability and proliferation. Results: Tumor weight
      significantly decreased following therapeutic dosing with zymosan (P < 0.05).
      This was associated with zymosan-induced upregulation of TLR-2, TLR-4 and TNF
      alpha mRNA in peritoneal macrophages and enhanced serum TNF-alpha levels (P <
      0.05). Splenocyte number and viability were increased in a concentration
      dependent manner by zymosan. Conclusions: Our study suggests that zymosan-induced
      upregulation of TLR-2, TLR-4 and TNF-alpha gene expression and of TNF-alpha
      release; together with increased level of lymphocyte proliferation may play a
      role in the inhibition of melanoma progression.

PMID- 29588629
TI  - Digital Technologies Supporting Person-Centered Integrated Care - A Perspective.
AB  - Shared electronic health and social care records in some service systems are
      already showing some of the benefits of digital technology and digital data for
      integrating health and social care. These records are one example of the
      beginning "digitalisation" of services that gives a glimpse of the potential of
      digital technology and systems for building coordinated and individualized
      integrated care. Yet the promise has been greater than the benefits, and progress
      has been slow compared to other industries. This paper describes for non
      technical readers how information technology was used to support integrated care
      schemes in six EU services, and suggests practical ways forward to use the new
      opportunities to build person-centered integrated care.

PMID- 29588628
TI  - A robust mass spectrometry method for rapid profiling of erythrocyte ghost
      membrane proteomes.
AB  - Background: Red blood cell (RBC) physiology is directly linked to many human
      disorders associated with low tissue oxygen levels or anemia including chronic
      obstructive pulmonary disease, congenital heart disease, sleep apnea and sickle
      cell anemia. Parasites such as Plasmodium spp. and phylum Apicomplexa directly
      target RBCs, and surface molecules within the RBC membrane are critical for
      pathogen interactions. Proteomics of RBC membrane 'ghost' fractions has therefore
      been of considerable interest, but protocols described to date are either
      suboptimal or too extensive to be applicable to a larger set of clinical cohorts.
      Methods: Here, we describe an optimised erythrocyte isolation protocol from
      blood, tested for various storage conditions and explored using different
      fractionation conditions for isolating ghost RBC membranes. Liquid chromatography
      mass spectrometry (LC-MS) analysis on a Q-Exactive Orbitrap instrument was used
      to profile proteins isolated from the comparative conditions. Data analysis was
      run on the MASCOT and MaxQuant platforms to assess their scope and diversity.
      Results: The results obtained demonstrate a robust method for membrane enrichment
      enabling consistent MS based characterisation of > 900 RBC membrane proteins in
      single LC-MS/MS analyses. Non-detergent based membrane solubilisation methods
      using the tissue and supernatant fractions of isolated ghost membranes are shown
      to offer effective haemoglobin removal as well as diverse recovery including
      erythrocyte membrane proteins of high and low abundance. Conclusions: The methods
      described in this manuscript propose a medium to high throughput framework for
      membrane proteome profiling by LC-MS of potential applicability to larger
      clinical cohorts in a variety of disease contexts.

PMID- 29588630
TI  - How to Improve Integrated Care for People with Chronic Conditions: Key Findings
      from EU FP-7 Project INTEGRATE and Beyond.
AB  - Background: Political and public health leaders increasingly recognize the need
      to take urgent action to address the problem of chronic diseases and multi
      morbidity. European countries are facing unprecedented demand to find new ways to
      deliver care to improve patient-centredness and personalization, and to avoid
      unnecessary time in hospitals. People-centred and integrated care has become a
      central part of policy initiatives to improve the access, quality, continuity,
      effectiveness and sustainability of healthcare systems and are thus preconditions
      for the economic sustainability of the EU health and social care systems.
      Purpose: This study presents an overview of lessons learned and critical success
      factors to policy making on integrated care based on findings from the EU FP-7
      Project Integrate, a literature review, other EU projects with relevance to this
      study, a number of best practices on integrated care and our own experiences with
      research and policy making in integrated care at the national and international
      level. Results: Seven lessons learned and critical success factors to policy
      making on integrated care were identified. Conclusion: The lessons learned and
      critical success factors to policy making on integrated care show that a
      comprehensive systems perspective should guide the development of integrated care
      towards better health practices, education, research and policy.

PMID- 29588631
TI  - A Policy Guide on Integrated Care (PGIC): Lessons Learned from EU Project
      INTEGRATE and Beyond.
AB  - Efforts are underway in many European countries to channel efforts into creating
      improved integrated health and social care services. But most countries lack a
      strategic plan that is sustainable over time, and that reflects a comprehensive
      systems perspective. The Policy Guide on Integrated Care (PGIC) as presented in
      this paper resulted from experiences with the EU Project INTEGRATE and our own
      work with healthcare reform for patients with chronic conditions at the national
      and international level. This project is one of the largest EU funded projects on
      Integrated Care, conducted over a four-year period (2012-2016) and included
      partners from nine European countries. Project Integrate aimed to gain insights
      into the leadership, management and delivery of integrated care to support
      European care systems to respond to the challenges of ageing populations and the
      rise of people living with long-term conditions. The objective of this paper is
      to describe the PGIC as both a tool and a reasoning flow that aims at supporting
      policy makers at the national and international level with the development and
      implementation of integrated care. Any Policy Guide on Integrated should build
      upon three building blocks, being a mission, vision and a strategy that aim at
      capturing the large amount of factors that directly or indirectly influence the
      successful development of integrated care.

PMID- 29588632
TI  - Interprofessional Collaboration between General Physicians and Emergency
      Department Teams in Belgium: A Qualitative Study.
AB  - This study aimed to assess interprofessional collaboration between general
      physicians and emergency departments in the French speaking regions of Belgium.
      Eight group interviews were conducted both in rural and urban areas, including in
      Brussels. Findings showed that the relational components of collaboration, which
      are highly valued by individuals involved, comprise mutual acquaintanceship and
      trust, shared power and objectives. The organizational components of
      collaboration included out-of-hours services, role clarification, leadership and
      overall environment. Communication and patient's role were also found to be key
      elements in enhancing or hindering collaboration across these two levels of care.
      Relationships between general physicians and emergency departments' teams were
      tightly linked to organizational factors and the general macro-environment.
      Health system regulation did not appear to play a significant role in promoting
      collaboration between actors. A better role clarification is needed in order to
      foster multidisciplinary team coordination for a more efficient patient
      management. Finally, economic power and private practice impeded
      interprofessional collaboration between the care teams. In conclusion, many
      challenges need to be addressed for achievement of a better collaboration and
      more efficient integration. Not only should integration policies aim at
      reinforcing the role of general physicians as gatekeepers, also they should
      target patients' awareness and empowerment.

PMID- 29588633
TI  - Longing for Integrated Care: The Importance of Effective Governance.

PMID- 29588634
TI  - Planning for the Discharge, not for Patient Self-Management at Home - An
      Observational and Interview Study of Hospital Discharge.
AB  - Introduction and objective: Despite recent interest in care transitions, little
      is known about how patients are prepared for the self-management tasks following
      the hospitalization. The objective of the study was to explore how discharge
      information is prepared and provided to patients in the transition from hospital
      to home. Method: The discharge process at three hospitals in Sweden was observed
      over 12 days spread over ten weeks. In total, 30 discharge encounters were
      observed followed by interviews with patients and professionals. Data were
      analysed using qualitative content analysis. Results: Much time, effort and
      resources were used to prepare the discharge; home-going teams and registered
      nurses planned the practical and social aspects of the discharge and the
      physicians compiled a plain-language discharge letter. Less focus was given on
      the actual discharge information to the patients. The discharge encounters lasted
      for a median of 4:46 minutes and the information had a retrospective focus with
      information on the hospitalization period, though omitting self-management tasks
      and life-style advice. Conclusion: The discharge letter constitutes the basis for
      all patient information at discharge. The focus of the discharge encounter needs
      to be extended beyond mere information to include patient understanding,
      motivation and skills for self-management at home.

PMID- 29588635
TI  - Individualising Chronic Care Management by Analysing Patients' Needs - A Mixed
      Method Approach.
AB  - Background: Modern health systems are increasingly faced with the challenge to
      provide effective, affordable and accessible health care for people with chronic
      conditions. As evidence on the specific unmet needs and their impact on health
      outcomes is limited, practical research is needed to tailor chronic care to
      individual needs of patients with diabetes. Qualitative approaches to describe
      professional and informal caregiving will support understanding the complexity of
      chronic care. Results are intended to provide practical recommendations to be
      used for systematic implementation of sustainable chronic care models. Method: A
      mixed method study was conducted. A standardised survey (n = 92) of experts in
      chronic care using mail responses to open-ended questions was conducted to
      analyse existing chronic care programs focusing on effective, problematic and
      missing components. An expert workshop (n = 22) of professionals and scientists
      of a European funded research project MANAGE CARE was used to define a limited
      number of unmet needs and priorities of elderly patients with type 2 diabetes
      mellitus and comorbidities. This list was validated and ranked using a
      multilingual online survey (n = 650). Participants of the online survey included
      patients, health care professionals and other stakeholders from 56 countries.
      Results: The survey indicated that current care models need to be improved in
      terms of financial support, case management and the consideration of social care.
      The expert workshop identified 150 patient needs which were summarised in 13
      needs dimensions. The online survey of these pre-defined dimensions revealed that
      financial issues, education of both patients and professionals, availability of
      services as well as health promotion are the most important unmet needs for both
      patients and professionals. Conclusion: The study uncovered competing demands
      which are not limited to medical conditions. The findings emphasise that future
      care models need to focus stronger on individual patient needs and promote their
      active involvement in co-design and implementation. Future research is needed to
      develop new chronic care models providing evidence-based and practical
      implications for the regional care setting.

PMID- 29588636
TI  - Enhancing Care Transitions for Older People through Interprofessional Simulation:
      A Mixed Method Evaluation.
AB  - Introduction: The educational needs of the health and social care workforce for
      delivering effective integrated care are important. This paper reports on the
      development, pilot and evaluation of an interprofessional simulation course,
      which aimed to support integrated care models for care transitions for older
      people from hospital to home. Theory and methods: The course development was
      informed by a literature review and a scoping exercise with the health and social
      care workforce. The course ran six times and was attended by health and social
      care professionals from hospital and community (n = 49). The evaluation aimed to
      elicit staff perceptions of their learning about care transfers of older people
      and to explore application of learning into practice and perceived outcomes. The
      study used a sequential mixed method design with questionnaires completed pre (n
      = 44) and post (n = 47) course and interviews (n = 9) 2-5 months later. Results:
      Participants evaluated interprofessional simulation as a successful strategy.
      Post-course, participants identified learning points and at the interviews,
      similar themes with examples of application in practice were: Understanding
      individual needs and empathy; Communicating with patients and families;
      Interprofessional working; Working across settings to achieve effective care
      transitions. Conclusions and discussion: An interprofessional simulation course
      successfully brought together health and social care professionals across
      settings to develop integrated care skills and improve care transitions for older
      people with complex needs from hospital to home.

PMID- 29588639
TI  - Contract Design: The problem of information asymmetry.
AB  - Introduction: Integrated care systems are advocated as an effective method of
      improving the performance of healthcare systems. These systems outline a payment
      and care delivery model that intends to tie provider reimbursements to predefined
      quality metrics. Little is known about the contractual design and the main
      challenges of delegating "accountability" to these new kinds of organisations
      and/or contracts. The research question in this article focuses on how healthcare
      contracts can look like and which possible problems arise in designing such
      contracts. In this a special interest is placed on information asymmetries.
      Methods: A comprehensive literature review on methods of designing contracts in
      Integrated Care was conducted. This article is the first in a row of three that
      all contribute to a specific issue in designing healthcare contracts. Starting
      with the organisation of contracts and information asymmetries, part 2 focusses
      on financial options and risks and part 3 finally concludes with the question of
      risk management and evaluation. Results: Healthcare contracting between providers
      and payers will have a major impact on the overall design of future healthcare
      systems. If Integrated care systems or any other similar concept of care delivery
      are to be contracted directly by payers to manage the continuum of care the costs
      of market utilisation play an essential role. Transaction costs also arise in the
      course of the negotiation and implementation of contracts. These costs are the
      reason why it is generally not possible to conclude perfect (complete) contracts.
      Problems with asymmetric distribution of information can relate to the situation
      before a contract is concluded (adverse selection) and after conclusion of a
      contract (moral hazard). Discussion and Conclusions: Information asymmetries are
      seen as a major obstacle to the efficient operation of integrated care
      programmes. Coordination and motivation problems cannot be solved at no-costs.
      The presented problems in the design of selective individual contracts represent
      a necessary but not a sufficient condition for further government intervention. A
      state or political failures have to be assumed continuously.

PMID- 29588637
TI  - Indicators and Measurement Tools for Health Systems Integration: A Knowledge
      Synthesis.
AB  - Background: Despite far reaching support for integrated care, conceptualizing and
      measuring integrated care remains challenging. This knowledge synthesis aimed to
      identify indicator domains and tools to measure progress towards integrated care.
      Methods: We used an established framework and a Delphi survey with integration
      experts to identify relevant measurement domains. For each domain, we searched
      and reviewed the literature for relevant tools. Findings: From 7,133 abstracts,
      we retrieved 114 unique tools. We found many quality tools to measure care
      coordination, patient engagement and team effectiveness/performance. In contrast,
      there were few tools in the domains of performance measurement and information
      systems, alignment of organizational goals and resource allocation. The search
      yielded 12 tools that measure overall integration or three or more indicator
      domains. Discussion: Our findings highlight a continued gap in tools to measure
      foundational components that support integrated care. In the absence of such
      targeted tools, "overall integration" tools may be useful for a broad assessment
      of the overall state of a system. Conclusions: Continued progress towards
      integrated care depends on our ability to evaluate the success of strategies
      across different levels and context. This study has identified 114 tools that
      measure integrated care across 16 domains, supporting efforts towards a unified
      measurement framework.

PMID- 29588640
TI  - Contract Design: Financial Options and Risk.
AB  - Introduction: Integrated care systems as well as accountable care organisations
      (ACOs) in the US and similar concepts in other countries are advocated as an
      effective method of improving the performance of healthcare systems. These
      systems outline a payment and care delivery model that intends to tie provider
      reimbursements to predefined quality metrics. By this the total costs of care
      shall be reduced. When designing healthcare options contractors are faced with a
      variety of financial options. The costs of market utilisation are highly relevant
      for the conception of healthcare contracts; furthermore contract-specific
      investments are an obstacle to the efficient operation of ACOs. Methods: A
      comprehensive literature review on methods of designing contracts in Integrated
      Care was conducted. This article is the second in a row of three that are all
      published in this issue and contribute to a specific issue in designing
      healthcare contracts. The first dealt with the organisation of contracts and
      information asymmetries, while part 3 concludes with the question of risk
      management and evaluation. The specific research question of this second article
      focusses on the financial options and reimbursement schemes that are available to
      define healthcare contracts. Results: A healthcare contract is a relational
      contract, which determines the level of reimbursement, the scope of services and
      the quality between service providers and payers, taking account of the risks
      relating to population and performance. A relational contract is an agreement
      based upon assumption of a longer timeframe. A major obstacle to the practical
      implementation of healthcare contracts is the prognosis of the inflows and
      outflows due to the actuarial risks of the insured population. Financing
      conditions and reimbursement arrangements that are based on a prospectively
      determined fixed price, have a significant drawback: it is very difficult to take
      the differences in health status and the utilisation of distinct insured
      clientele (panel) into account. Discussion and Conclusion: The first two articles
      of this series on contract design have shown that complete contracts in
      healthcare are unrealistic. Healthcare reimbursement contracts are incomplete
      contracts with a high degree of uncertainty. In incomplete contracts specific
      contractual regulations are not made for any eventuality. For this reason it is
      important that the parties agree on the prevention of endogenous risks
      (asymmetric information after the conclusion of the contract) and on the
      procedure in the case of unforeseen circumstances (the risks of random, parameter
      risk and change risks to the healthcare program).

PMID- 29588641
TI  - Cancer Survivorship Care: Person Centered Care in a Multidisciplinary Shared Care
      Model.
AB  - Survivors of childhood and adult-onset cancer are at lifelong risk for the
      development of late effects of treatment that can lead to serious morbidity and
      premature mortality. Regular long-term follow-up aiming for prevention, early
      detection and intervention of late effects can preserve or improve health. The
      heterogeneous and often serious character of late effects emphasizes the need for
      specialized cancer survivorship care clinics. Multidisciplinary cancer
      survivorship care requires a coordinated and well integrated health care
      environment for risk based screening and intervention. In addition survivors
      engagement and adherence to the recommendations are also important elements. We
      developed an innovative model for integrated care for cancer survivors, the
      "Personalized Cancer Survivorship Care Model", that is being used in our clinic.
      This model comprises 1. Personalized follow-up care according to the principles
      of Person Centered Care, aiming to empower survivors and to support self
      management, and 2. Organization according to a multidisciplinary and risk based
      approach. The concept of person centered care is based on three components:
      initiating, integrating and safeguarding the partnership with the patient. This
      model has been developed as a universal model of care that will work for all
      cancer survivors in different health care systems. It could be used for studies
      to improve self efficacy and the cost-effectiveness of cancer survivorship care.

PMID- 29588638
TI  - Integrated Care Planning for Cancer Patients: A Scoping Review.
AB  - Introduction: There has been a growing emphasis on the use of integrated care
      plans to deliver cancer care. However little is known about how integrated care
      plans for cancer patients are developed including featured core activities,
      facilitators for uptake and indicators for assessing impact. Methods: Given
      limited consensus around what constitutes an integrated care plan for cancer
      patients, a scoping review was conducted to explore the components of integrated
      care plans and contextual factors that influence design and uptake. Results: Five
      types of integrated care plans based on the stage of cancer care: surgical,
      systemic, survivorship, palliative and comprehensive (involving a transition
      between stages) are described in current literature. Breast, esophageal and
      colorectal cancers were common disease sites. Multi-disciplinary teams, patient
      needs assessment and transitional planning emerged as key features. Provider buy
      in and training alongside informational technology support served as important
      facilitators for plan uptake. Provider-level measurement was considerably less
      robust compared to patient and system-level indicators. Conclusions: Similarities
      in design features, components and facilitators across the various types of
      integrated care plans indicates opportunities to leverage shared features and
      enable a management lens that spans the trajectory of a patient's journey rather
      than a phase-specific silo approach to care.

PMID- 29588642
TI  - Quasi-experimental Study of Systematic Screening for Family Planning Services
      among Postpartum Women Attending Village Health and Nutrition Days in Jharkhand,
      India.
AB  - Background: Systematic screening helps increase family planning uptake through
      integration with other services, including immunization. Though successfully
      demonstrated at health facilities, this strategy has not been demonstrated in
      communities. This study assessed the effectiveness of systematic screening to
      increase postpartum family planning use during community health days in India
      without adversely affecting immunization services. Methods: The study was
      conducted during 180 individual Village Health and Nutrition Days in Jharkhand,
      India. All health workers were trained in postpartum family planning counseling.
      Intervention providers were also trained in systematic screening. 217 postpartum
      women aged 15-49 years participated in baseline and endline exit interviews and
      routine service statistics were analyzed from 2,485 facility visits at affiliated
      health centers. Results: No difference in family planning service use was found
      in the intervention group, but significantly fewer interviewed women reported
      receiving family planning services at endline in the comparison group (p =
      0.014). Family planning acceptance at affiliated health centers increased
      significantly in intervention areas (p < 0.001) but not in comparison areas,
      while immunization service use increased in both groups (p = 0.002 intervention,
      p < 0.001 comparison). Conclusions: The use of the postpartum systematic
      screening tool appears to increase acceptance of family planning services when
      integrated with community-based services in Jharkhand.

PMID- 29588643
TI  - Integrated Care to Address the Physical Health Needs of People with Severe Mental
      Illness: A Mapping Review of the Recent Evidence on Barriers, Facilitators and
      Evaluations.
AB  - People with mental health conditions have a lower life expectancy and poorer
      physical health outcomes than the general population. Evidence suggests this is
      due to a combination of clinical risk factors, socioeconomic factors, and health
      system factors, notably a lack of integration when care is required across
      service settings. Several recent reports have looked at ways to better integrate
      physical and mental health care for people with severe mental illness (SMI). We
      built on these by conducting a mapping review that looked for the most recent
      evidence and service models in this area. This involved searching the published
      literature and speaking to people involved in providing or using current
      services. Few of the identified service models were described adequately and
      fewer still were evaluated, raising questions about the replicability and
      generalisability of much of the existing evidence. However, some common themes
      did emerge. Efforts to improve the physical health care of people with SMI should
      empower staff and service users and help remove everyday barriers to delivering
      and accessing integrated care. In particular, there is a need for improved
      communication among professionals and better information technology to support
      them, greater clarity about who is responsible and accountable for physical
      health care, and greater awareness of the effects of stigmatisation on the wider
      culture and environment in which services are delivered.

PMID- 29588644
TI  - An Instrument to Measure Maturity of Integrated Care: A First Validation Study.
AB  - Introduction: Lessons captured from interviews with 12 European regions are
      represented in a new instrument, the B3-Maturity Model (B3-MM). B3-MM aims to
      assess maturity along 12 dimensions reflecting the various aspects that need to
      be managed in order to deliver integrated care. The objective of the study was to
      test the content validity of B3-MM as part of SCIROCCO (Scaling Integrated Care
      into Context), a European Union funded project. Methods: A literature review was
      conducted to compare B3-MM's 12 dimensions and their measurement scales with
      existing measures and instruments that focus on assessing the development of
      integrated care. Subsequently, a three-round survey conducted through a Delphi
      study with international experts in the field of integrated care was performed to
      test the relevance of: 1) the dimensions, 2) the maturity indicators and 3) the
      assessment scale used in B3-MM. Results: The 11 articles included in the
      literature review confirmed all the dimensions described in the original version
      of B3-MM. The Delphi study rounds resulted in various phrasing amendments of
      indicators and assessment scale. Full agreement among the experts on the
      relevance of the 12 B3-MM dimensions, their indicators, and assessment scale was
      reached after the third Delphi round. Conclusion and discussion: The B3-MM
      dimensions, maturity indicators and assessment scale showed satisfactory content
      validity. While the B3-MM is a unique instrument based on existing knowledge and
      experiences of regions in integrated care, further testing is needed to explore
      other measurement properties of B3-MM.

PMID- 29588645
TI  - Translating the Elements of Health Governance for Integrated Care from Theory to
      Practice: A Case Study Approach.
AB  - Introduction: Against a paucity of evidence, a model describing elements of
      health governance best suited to achieving integrated care internationally was
      developed. The aim of this study was to explore how health meso-level
      organisations used, or planned to use, the governance elements. Methods: A case
      study design was used to offer two contrasting contexts of health governance.
      Semi-structured interviews were conducted with participants who held senior
      governance roles. Data were thematically analysed to identify if the elements of
      health governance were being used, or intended to be in the future. Results:
      While all participants agreed that the ten elements were essential to developing
      future integrated care, most were not used. Three major themes were identified:
      (1) organisational versus system focus, (2) leadership and culture, and, (3)
      community (dis)engagement. Discussion: Several barriers and enablers to the use
      of the elements were identified and would require addressing in order to make
      evidence-based changes. Conclusion: Despite a clear international policy
      direction in support of integrated care this study identified a number of
      significant barriers to its implementation. The study reconfirmed that a focus on
      all ten elements of health governance is essential to achieve integrated care.

PMID- 29588646
TI  - Patient Involvement in Geriatric Care - Results and Experiences from a Mixed
      Models Design Study within Project INTEGRATE.
AB  - Introduction: Patient involvement is a core component of an integrated care
      approach. While the benefits and prerequisites of patient involvement have been
      described in general and additionally for some target populations, little is
      known about the views and experiences of older people regarding this matter.
      Methods: A study with a mixed-methods design was conducted to gain a better
      understanding about patient involvement in geriatric care. A questionnaire on
      shared decision-making was administered within a group of older adults in
      Germany. Additionally, 7 focus groups with health professionals and geriatric
      patients in Germany and Estonia were held to deepen the insight of the
      questionnaire and discussing experiences and barriers of patient involvement.
      Results: Older people without an actual medical problem expressed a significantly
      higher desire to participate in shared decisions than those requiring actual
      medical care. No significant differences could be found for the desire to be
      informed as part of the care process. No correlation between patients' desire and
      experiences on shared decision-making could be observed. In the focus groups,
      patients demanded a comprehensive and understandable information and education
      process while the health professionals' view was very task-specific. This
      conflict led to a loss of trust by the patients. Conclusions: There is a gap
      between patients' and health professionals' views on patient involvement in older
      people. The involvement process should therefore be comprehensive and should take
      into account different levels of health literacy.

PMID- 29588648
TI  - Flexibility of foraging strategies of the great skua Stercorarius skua breeding
      in the largest colony in the Barents Sea region.
AB  - Background: Foraging strategies of seabird species often vary considerably
      between and within individuals. This variability is influenced by a multitude of
      factors including age, sex, stage of annual life cycle, reproductive status,
      individual specialization and environmental conditions. Results: Using GPS
      loggers, we investigated factors affecting foraging flight characteristics (total
      duration, maximal range, total distance covered) of great skuas Stercorarius skua
      of known sex breeding on Bjornoya, Svalbard, the largest colony in the Barents
      Sea region. We examined influence of sex (females are larger than males), phase
      of breeding (incubation, chick-rearing), reproductive status (breeders, failed
      breeders) and bird ID (they are known for individual foraging specialization).
      Our analyses revealed that only bird ID affected foraging flight characteristics
      significantly, indicating a high degree of plasticity regardless of sex,
      reproductive status or phase of breeding. We recognized three main groups of
      individuals: 1) those preying mainly on other seabirds in the breeding colonies
      (6%), 2) those foraging at sea (76%) and kleptoparasiting other seabirds and/or
      foraging on fish and/or offal discarded by fishing vessels, and 3) those
      alternating between preying on other seabirds in breeding colonies and foraging
      at sea (18%). Despite marked size sexual dimorphism, we found no apparent sex
      differences in flight characteristics. Birds after egg- or chick-loss and thus
      not constrained as central foragers did not modify their foraging flights.
      Conclusions: Great skuas breeding on Bjornoya displayed a high degree of
      plasticity regardless of sex, reproductive status or phase of breeding. We
      recognized groups of individuals regularly preying in the seabird colonies,
      foraging at sea, and alternating between both strategies. This suggests foraging
      specialization of some individuals.

PMID- 29588649
TI  - Classification of CITES-listed and other neotropical Meliaceae wood images using
      convolutional neural networks.
AB  - Background: The current state-of-the-art for field wood identification to combat
      illegal logging relies on experienced practitioners using hand lenses,
      specialized identification keys, atlases of woods, and field manuals.
      Accumulation of this expertise is time-consuming and access to training is
      relatively rare compared to the international demand for field wood
      identification. A reliable, consistent and cost effective field screening method
      is necessary for effective global scale enforcement of international treaties
      such as the Convention on the International Trade in Endagered Species (CITES) or
      national laws (e.g. the US Lacey Act) governing timber trade and imports.
      Results: We present highly effective computer vision classification models, based
      on deep convolutional neural networks, trained via transfer learning, to identify
      the woods of 10 neotropical species in the family Meliaceae, including CITES
      listed Swietenia macrophylla, Swietenia mahagoni, Cedrela fissilis, and Cedrela
      odorata. We build and evaluate models to classify the 10 woods at the species and
      genus levels, with image-level model accuracy ranging from 87.4 to 97.5%, with
      the strongest performance by the genus-level model. Misclassified images are
      attributed to classes consistent with traditional wood anatomical results, and
      our species-level accuracy greatly exceeds the resolution of traditional wood
      identification. Conclusion: The end-to-end trained image classifiers that we
      present discriminate the woods based on digital images of the transverse surface
      of solid wood blocks, which are surfaces and images that can be prepared and
      captured in the field. Hence this work represents a strong proof-of-concept for
      using computer vision and convolutional neural networks to develop practical
      models for field screening timber and wood products to combat illegal logging.

PMID- 29588650
TI  - Outlier detection in BLAST hits.
AB  - Background: An important task in a metagenomic analysis is the assignment of
      taxonomic labels to sequences in a sample. Most widely used methods for taxonomy
      assignment compare a sequence in the sample to a database of known sequences.
      Many approaches use the best BLAST hit(s) to assign the taxonomic label. However,
      it is known that the best BLAST hit may not always correspond to the best
      taxonomic match. An alternative approach involves phylogenetic methods, which
      take into account alignments and a model of evolution in order to more accurately
      define the taxonomic origin of sequences. Similarity-search based methods
      typically run faster than phylogenetic methods and work well when the organisms
      in the sample are well represented in the database. In contrast, phylogenetic
      methods have the capability to identify new organisms in a sample but are
      computationally quite expensive. Results: We propose a two-step approach for
      metagenomic taxon identification; i.e., use a rapid method that accurately
      classifies sequences using a reference database (this is a filtering step) and
      then use a more complex phylogenetic method for the sequences that were
      unclassified in the previous step. In this work, we explore whether and when
      using top BLAST hit(s) yields a correct taxonomic label. We develop a method to
      detect outliers among BLAST hits in order to separate the phylogenetically most
      closely related matches from matches to sequences from more distantly related
      organisms. We used modified BILD (Bayesian Integral Log-Odds) scores, a multiple
      alignment scoring function, to define the outliers within a subset of top BLAST
      hits and assign taxonomic labels. We compared the accuracy of our method to the
      RDP classifier and show that our method yields fewer misclassifications while
      properly classifying organisms that are not present in the database. Finally, we
      evaluated the use of our method as a pre-processing step before more expensive
      phylogenetic analyses (in our case TIPP) in the context of real 16S rRNA
      datasets. Conclusion: Our experiments make a good case for using a two-step
      approach for accurate taxonomic assignment. We show that our method can be used
      as a filtering step before using phylogenetic methods and provides a way to
      interpret BLAST results using more information than provided by E-values and bit
      scores alone.

PMID- 29588647
TI  - STAT3, stem cells, cancer stem cells and p63.
AB  - Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription
      factor with many important functions in the biology of normal and transformed
      cells. Its regulation is highly complex as it is involved in signaling pathways
      in many different cell types and under a wide variety of conditions. Besides
      other functions, STAT3 is an important regulator of normal stem cells and cancer
      stem cells. p63 which is a member of the p53 protein family is also involved in
      these functions and is both physically and functionally connected with STAT3.
      This review summarizes STAT3 function and regulation, its role in stem cell and
      cancer stem cell properties and highlights recent reports about its relationship
      to p63.

PMID- 29588651
TI  - FSH: fast spaced seed hashing exploiting adjacent hashes.
AB  - Background: Patterns with wildcards in specified positions, namely spaced seeds,
      are increasingly used instead of k-mers in many bioinformatics applications that
      require indexing, querying and rapid similarity search, as they can provide
      better sensitivity. Many of these applications require to compute the hashing of
      each position in the input sequences with respect to the given spaced seed, or to
      multiple spaced seeds. While the hashing of k-mers can be rapidly computed by
      exploiting the large overlap between consecutive k-mers, spaced seeds hashing is
      usually computed from scratch for each position in the input sequence, thus
      resulting in slower processing. Results: The method proposed in this paper, fast
      spaced-seed hashing (FSH), exploits the similarity of the hash values of spaced
      seeds computed at adjacent positions in the input sequence. In our experiments we
      compute the hash for each positions of metagenomics reads from several datasets,
      with respect to different spaced seeds. We also propose a generalized version of
      the algorithm for the simultaneous computation of multiple spaced seeds hashing.
      In the experiments, our algorithm can compute the hashing values of spaced seeds
      with a speedup, with respect to the traditional approach, between 1.6[Formula:
      see text] to 5.3[Formula: see text], depending on the structure of the spaced
      seed. Conclusions: Spaced seed hashing is a routine task for several
      bioinformatics application. FSH allows to perform this task efficiently and raise
      the question of whether other hashing can be exploited to further improve the
      speed up. This has the potential of major impact in the field, making spaced seed
      applications not only accurate, but also faster and more efficient. Availability:
      The software FSH is freely available for academic use at:
      https://bitbucket.org/samu661/fsh/overview.

PMID- 29588652
TI  - What is the treatment of tracheal lesions associated with traditional
      thyroidectomy? Case report and systematic review.
AB  - Aim: The aim of this study is to review the literature focusing on various
      treatments based on time of tracheal injury and on different surgeons' personal
      experience. Methods: We retrospectively reviewed all cases of total thyroidectomy
      performed at the University Surgical Department of Ospedali Riuniti of Foggia
      from 2006 to 2017. Only a single case of tracheal lesion due to traditional total
      thyroidectomy was found. An extensive search of the relevant literature was
      carried out using MEDLINE (PubMed). We included articles that reported article
      type, patient number, sex, age, reasons for surgery, time of tracheal perforation
      intraoperatively or delayed rupture, symptoms, diagnosis, type of surgical
      procedure, pathological report and follow-up. Results: A total of 156 published
      studies were screened from the sources listed. Of these, 15 studies were included
      in the present study. We introduced our case in the analysis. A total of 16
      patients were totally analysed. There were seven males (43.7%) and seven females
      (43.7%), and for two patients, gender was not available. The mean patient age was
      41.6 years. Conclusions: The literature review showed very few cases treated
      differently. However, it would be good to standardise treatments. Tracheal
      perforation, if encountered, needs to be managed appropriately in centres of
      expertise with a high volume of thyroidectomies.

PMID- 29588653
TI  - Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up,
      top-down-and meeting in the middle.
AB  - Investigating the pharmacology is key to the modernization of Chinese Medicine
      (CM) formulas. However, identifying which are the active compound(s) of CM
      formulas, which biological entities they target, and through which signaling
      pathway(s) they act to modify disease symptoms, are still difficult tasks for
      researchers, even when equipped with an arsenal of advanced modern technologies.
      Multiple approaches, including network pharmacology, pharmaco-genomics, 
      proteomics, and -metabolomics, have been developed to study the pharmacology of
      CM formulas. They fall into two general categories in terms of how they tackle a
      problem: bottom-up and top-down. In this article, we compared these two different
      approaches in several dimensions by using the case of MaZiRenWan (MZRW, also
      known as Hemp Seed Pill), a CM herbal formula for functional constipation.
      Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g.
      network pharmacology); but these hypotheses are usually false positives and hard
      to be tested. In contrast, it is hard to suggest hypotheses in the top-down
      approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it
      is much easier to be tested. Merging of these two approaches could results in a
      powerful approach, which could be the new paradigm for the pharmacological study
      of CM formulas.

PMID- 29588654
TI  - Psoriasis therapy by Chinese medicine and modern agents.
AB  - Psoriasis is a chronic, painful, disfiguring and non-contagious skin disease that
      has globally affected at least 200 million patients. In general, mild to moderate
      psoriasis patients will be treated by chemical drugs or Chinese medicine, while
      targeting systemic biological drugs have been successfully developed with good
      efficacy but high cost burden to patients with severe psoriasis. Since the
      underlying mechanisms of psoriasis are not well understood, in this review,
      psoriasis pathogenesis and clinical therapeutic principles by modern medicine and
      Chinese medicine are extensively described. Based on the data from the China Food
      and Drug Administration, the majority of chemical drugs are utilized as the
      topical formulations, while Chinese medicines are mainly delivered by an oral
      route, suggesting that the market for topical preparations of Chinese medicine to
      treat psoriasis is worth to exploration. Moreover, considering the unique
      clinical therapeutic theory and successful clinical application of Chinese
      medicine in the treatment of psoriasis, we believe that development of new small
      molecule drugs based on Chinese medicine will be a promising strategy to reduce
      therapeutic costs and improve safety for psoriatic patients.

PMID- 29588655
TI  - Reflections from the Lebanese field: "First, heal thyself".
AB  - Humanitarian aid workers caring for Syrian refugees face major stressors as they
      attend to refugees' needs on the field. Without adequate psychosocial support,
      evidence has shown that fieldworkers experience high burnout and turnover as well
      as long-term poor mental health. Unfortunately, scarce training in this regard
      leaves them ill-equipped to care for themselves and practice resilience while
      handling trauma in the field. This paper highlights our reflection on working
      with mindfulness programs during humanitarian crises, specifically how our
      program, Stress Management and Relaxation Response Training (SMART), has helped
      over time fieldworkers and the community they cared for. We propose that programs
      targeting the wellbeing of fieldworkers should be prioritized as part of efforts
      to improve the international aid response although they may require impeccable
      coordination and generous resources. We encourage donors to fund those projects
      viewed as special social protection programs building resilience and
      strengthening within system support. We argue that this will increase the
      efficacy of the crisis intervention and work towards sustainable peace building.

PMID- 29588656
TI  - Involuntary admission in Norwegian adult psychiatric hospitals: a systematic
      review.
AB  - Background: It is an important objective of the psychiatric services to keep the
      use of involuntary procedures to a minimum, as the use of coercion involves
      clinical, ethical, and legal issues. It has been claimed that Norway has a
      relatively high rate of involuntary admissions. We reviewed the peer-reviewed
      literature on the use of involuntary admission in Norway, with the purpose of
      identifying the current state of knowledge and areas in need of further research.
      Methods: A systematic review following the PRISMA statement was conducted. We
      searched the electronic databases PsycInfo, PubMed, Web of Science, CINAHL, and
      Embase for studies relating to involuntary admission to Norwegian adult
      psychiatric hospitals published in the period 1 January 2001 to 8 August 2016.
      The database searches were supplemented with manual searches of relevant
      journals, reference lists, and websites. Results: Seventy-four articles were
      included and grouped into six categories based on their main topics: Patients'
      experiences, satisfaction and perceived coercion (21 articles), the Referral and
      admission process (11 articles), Rates of admission (8 articles), Characteristics
      of the patients (17 articles), Staff attitudes (9 articles), and Outcomes (8
      articles). Four of the included articles described intervention studies. Fifty
      seven of the articles had a quantitative design, 16 had a qualitative design, and
      one a mixed-method design. There was a broad range of topics that were studied
      and considerable variation in study designs. The findings were largely in line
      with the international literature, but the particularities of Norwegian
      legislation and the Norwegian health services were reflected in the literature.
      The four intervention studies explored interventions for reducing rates of
      involuntary admission, such as modifying referring routines, improving patient
      information procedures, and increasing patients' say in the admission process,
      and represent an important avenue for future research on involuntary admission in
      Norway. Conclusions: The review suggests that Norway has a relatively high rate
      of involuntary admissions. The identified studies represent a broad mix of topics
      and designs. Four intervention studies were identified. More studies with strong
      designs are needed to bring research on involuntary admission in Norway to a next
      level.

PMID- 29588657
TI  - Feasibility study of a family- and school-based intervention for child behavior
      problems in Nepal.
AB  - Background: This study evaluates the feasibility, acceptability, and outcomes of
      a combined school- and family-based intervention, delivered by psychosocial
      counselors, for children with behavior problems in rural Nepal. Methods: Forty
      one children participated at baseline. Two students moved to another district,
      meaning 39 children, ages 6-15, participated at both baseline and follow-up. Pre
      post evaluation was used to assess behavioral changes over a 4-month follow-up
      period (n = 39). The primary outcome measure was the Disruptive Behavior
      International Scale-Nepal version (DBIS-N). The secondary outcome scales included
      the Child Functional Impairment Scale and the Eyberg Child Behavior Inventory
      (ECBI). Twelve key informant interviews were conducted with community
      stakeholders, including teachers, parents, and community members, to assess
      stakeholders' perceptions of the intervention. Results: The study found that
      children's behavior problems as assessed on the DBIS-N were significantly lower
      at follow-up (M = 13.0, SD = 6.4) than at baseline (M = 20.5, SD = 3.8), p <
      0.001, CI [5.57, 9.35]. Similarly, children's ECBI Intensity scores were
      significantly lower at follow-up (M = 9.9, SD = 8.5) than at baseline (M = 14.8,
      SD = 7.7), p < 0.005, 95% CI [1.76, 8.14]. The intervention also significantly
      improved children's daily functioning. Parents and teachers involved in the
      intervention found it acceptable and feasible for delivery to their children and
      students. Parents and teachers reported improved behaviors among children and the
      implementation of new behavior management techniques both at home and in the
      classroom. Conclusions: Significant change in child outcome measures in this
      uncontrolled evaluation, alongside qualitative findings suggesting feasibility
      and acceptability, support moving toward a controlled trial to determine
      effectiveness.

PMID- 29588658
TI  - From nano- to micrometer scale: the role of microwave-assisted acid and alkali
      pretreatments in the sugarcane biomass structure.
AB  - Background: To date, great strides have been made in elucidating the role of
      thermochemical pretreatments in the chemical and structural features of plant
      cell walls; however, there is no clear picture of the plant recalcitrance and its
      relationship to deconstruction. Previous studies precluded full answers due to
      the challenge of multiscale features of plant cell wall organization.
      Complementing the previous efforts, we undertook a systematic, multiscale, and
      integrated approach to track the effect of microwave-assisted H2SO4 and NaOH
      treatments on the hierarchical structure of plants, i.e., from a nano- to
      micrometer scale. We focused on the investigation of the highly recalcitrant
      sclerenchyma cell walls from sugarcane bagasse. Results: Through atomic force
      microscopy and X-ray diffraction analyses, remarkable details of the assembly of
      cellulose microfibrils not previously seen were revealed. Following the H2SO4
      treatment, we observed that cellulose microfibrils were almost double the width
      of the alkali pretreated sample at the temperature of 160  degrees C. Such
      enlargement led to a greater contact between cellulose chains, with a subsequent
      molecule alignment, as indicated by the X-ray diffraction (XRD) results with the
      conspicuous expansion of the average crystallite size. The delignification
      process had little effect on the local nanometer-sized arrangement of cellulose
      molecules. However, the rigidity and parallel alignment of cellulose microfibrils
      were partially degraded. The XRD analysis also agrees with these findings as
      evidenced by large momentum transfer vectors (q > 20 nm-1), interpreted as
      indicators of the long-range order of cell wall components, which were similar
      for all the studied samples except with application of the NaOH treatment at 160 
      degrees C. These changes were followed by the eventual swelling of the fiber cell
      walls. Conclusions: Based on an integrated approach, we presented
      multidimensional architectural models of cell wall deconstruction resulting from
      microwave-assisted pretreatments. We provided direct evidence supporting the idea
      that hemicellulose is the main barrier for the swelling of cellulose
      microfibrils, whereas lignin adds rigidity to cell walls. Our findings shed light
      on the design of more efficient strategies, not only for the conversion of
      biomass to fuels but also for the production of nanocellulose, which has great
      potential for several applications such as composites, rheology modifiers, and
      pharmaceuticals.

PMID- 29588659
TI  - A novel acetyl xylan esterase enabling complete deacetylation of substituted
      xylans.
AB  - Background: Acetylated 4-O-(methyl)glucuronoxylan (GX) is the main hemicellulose
      in deciduous hardwood, and comprises a beta-(1->4)-linked xylopyranosyl (Xylp)
      backbone substituted by both acetyl groups and alpha-(1->2)-linked 4-O
      methylglucopyranosyluronic acid (MeGlcpA). Whereas enzymes that target singly
      acetylated Xylp or doubly 2,3-O-acetyl-Xylp have been well characterized, those
      targeting (2-O-MeGlcpA)3-O-acetyl-Xylp structures in glucuronoxylan have remained
      elusive. Results: An unclassified carbohydrate esterase (FjoAcXE) was identified
      as a protein of unknown function from a polysaccharide utilization locus (PUL)
      otherwise comprising carbohydrate-active enzyme families known to target xylan.
      FjoAcXE was shown to efficiently release acetyl groups from internal (2-O
      MeGlcpA)3-O-acetyl-Xylp structures, an activity that has been sought after but
      lacking in known carbohydrate esterases. FjoAcXE action boosted the activity of
      alpha-glucuronidases from families GH67 and GH115 by five and nine times,
      respectively. Moreover, FjoAcXE activity was not only restricted to GX, but also
      deacetylated (3-O-Araf)2-O-acetyl-Xylp of feruloylated xylooligomers, confirming
      the broad substrate range of this new carbohydrate esterase. Conclusion: This
      study reports the discovery and characterization of the novel carbohydrate
      esterase, FjoAcXE. In addition to cleaving singly acetylated Xylp, and doubly 2,3
      O-acetyl-Xylp, FjoAcXE efficiently cleaves internal 3-O-acetyl-Xylp linkages in
      (2-O-MeGlcpA)3-O-acetyl-Xylp residues along with densely substituted and branched
      xylooligomers; activities that until now were missing from the arsenal of enzymes
      required for xylan conversion.

PMID- 29588660
TI  - Lignolytic-consortium omics analyses reveal novel genomes and pathways involved
      in lignin modification and valorization.
AB  - Background: Lignin is a heterogeneous polymer representing a renewable source of
      aromatic and phenolic bio-derived products for the chemical industry. However,
      the inherent structural complexity and recalcitrance of lignin makes its
      conversion into valuable chemicals a challenge. Natural microbial communities
      produce biocatalysts derived from a large number of microorganisms, including
      those considered unculturable, which operate synergistically to perform a variety
      of bioconversion processes. Thus, metagenomic approaches are a powerful tool to
      reveal novel optimized metabolic pathways for lignin conversion and valorization.
      Results: The lignin-degrading consortium (LigMet) was obtained from a sugarcane
      plantation soil sample. The LigMet taxonomical analyses (based on 16S rRNA)
      indicated prevalence of Proteobacteria, Actinobacteria and Firmicutes members,
      including the Alcaligenaceae and Micrococcaceae families, which were enriched in
      the LigMet compared to sugarcane soil. Analysis of global DNA sequencing revealed
      around 240,000 gene models, and 65 draft bacterial genomes were predicted. Along
      with depicting several peroxidases, dye-decolorizing peroxidases, laccases,
      carbohydrate esterases, and lignocellulosic auxiliary (redox) activities, the
      major pathways related to aromatic degradation were identified, including
      benzoate (or methylbenzoate) degradation to catechol (or methylcatechol),
      catechol ortho-cleavage, catechol meta-cleavage, and phthalate degradation. A
      novel Paenarthrobacter strain harboring eight gene clusters related to aromatic
      degradation was isolated from LigMet and was able to grow on lignin as major
      carbon source. Furthermore, a recombinant pathway for vanillin production was
      designed based on novel gene sequences coding for a feruloyl-CoA synthetase and
      an enoyl-CoA hydratase/aldolase retrieved from the metagenomic data set.
      Conclusion: The enrichment protocol described in the present study was successful
      for a microbial consortium establishment towards the lignin and aromatic
      metabolism, providing pathways and enzyme sets for synthetic biology engineering
      approaches. This work represents a pioneering study on lignin conversion and
      valorization strategies based on metagenomics, revealing several novel lignin
      conversion enzymes, aromatic-degrading bacterial genomes, and a novel bacterial
      strain of potential biotechnological interest. The validation of a biosynthetic
      route for vanillin synthesis confirmed the applicability of the targeted
      metagenome discovery approach for lignin valorization strategies.

PMID- 29588661
TI  - Enhancing the catalytic activity of a novel GH5 cellulase GtCel5 from
      Gloeophyllum trabeum CBS 900.73 by site-directed mutagenesis on loop 6.
AB  - Background: Cellulases of glycosyl hydrolase (GH) family 5 share a (beta/alpha)8
      TIM-barrel fold structure with eight betaalpha loops surrounding the catalytic
      pocket. These loops exposed on the surface play a vital role in protein
      functions, primarily due to the interactions of some key amino acids with solvent
      and ligand molecules. It has been reported that motions of these loops facilitate
      substrate access and product release, and loops 6 and 7 located at the substrate
      entrance of the binding pocket promote proton transfer reaction at the catalytic
      site motions. However, the role of these flexible loops in catalysis of GH5
      cellulase remains to be explored. Results: In the present study, an acidic,
      mesophilic GH5 cellulase (with optimal activity at pH 4.0 and 70  degrees C),
      GtCel5, was identified in Gloeophyllum trabeum CBS 900.73. The specific
      activities of GtCel5 toward CMC-Na, barley beta-glucan, and lichenan were 1117 +/
      43, 6257 +/- 26 and 5318 +/- 54 U/mg, respectively. Multiple sequence alignment
      indicates that one amino acid residue at position 233 on the loop 6 shows semi
      conservativeness and might contribute to the great catalytic performance.
      Saturation mutagenesis at position 233 was then conducted to reveal the vital
      roles of this position in enzyme properties. In comparison to the wild type,
      variants N233A and N233G showed decreased optimal temperature (- 10  degrees C)
      but increased activities (27 and 70%) and catalytic efficiencies (kcat/Km; 45 and
      52%), respectively. The similar roles of position 233 in catalytic performance
      were also verified in the other two GH5 homologs, TeEgl5A and PoCel5, by reverse
      mutation. Further molecular dynamics simulations suggested that the substitution
      of asparagine with alanine or glycine may introduce more hydrogen bonds, increase
      the flexibility of loop 6, enhance the interactions between enzyme and substrate,
      and thus improve the substrate affinity and catalytic efficiency. Conclusion:
      This study proposed a novel cellulase with potentials for industrial application.
      A specific position was identified to play key roles in cellulase-substrate
      interactions and enzyme catalysis. It is of great importance for understanding
      the binding mechanism of GH5 cellulases, and provides an effective strategy to
      improve the catalytic performance of cellulases.

PMID- 29588662
TI  - Bridging the gap between feedstock growers and users: the study of a coppice
      poplar-based biorefinery.
AB  - Background: In the biofuel industry, land productivity is important to feedstock
      growers and conversion process product yield is important to the biorefinery. The
      crop productivity, however, may not positively correlate with bioconversion
      yield. Therefore, it is important to evaluate sugar yield and biomass
      productivity. In this study, 2-year-old poplar trees harvested in the first
      coppice cycle, including one low-productivity hybrid and one high-productivity
      hybrid, were collected from two poplar tree farms. Through steam pretreatment and
      enzymatic hydrolysis, the bioconversion yields of low- and high-productivity
      poplar hybrids were compared for both sites. Results: The low-productivity
      hybrids had 9-19% higher sugar yields than the high-productivity hybrids,
      although they have the similar chemical composition. Economic calculations show
      the impact on the plantation and biorefinery of using the two feedstocks. Growing
      a high-productivity hybrid means the land owner would use 11-26% less land (which
      could be used for other crops) or collect $2.53-$3.46 MM/year extra revenue from
      the surplus feedstock. On the other side, the biorefinery would receive 5-10%
      additional revenue using the low-productivity hybrid. Conclusion: We propose a
      business model based on the integration of the plantation and the biorefinery. In
      this model, different feedstocks are assessed using a metric of product tonnage
      per unit land per year. Use of this new economic metric bridges the gap between
      feedstock growers and users to maximize the overall production efficiency.

PMID- 29588663
TI  - A long noncoding RNA promotes cellulase expression in Trichoderma reesei.
AB  - Background: Due to its capability to secrete large quantities of plant biomass
      degrading enzymes (PBDE), Trichoderma reesei is widely applied for industrial
      purposes. In nature, expression of PBDE is efficiently regulated in this fungus.
      Several factors involved in this regulatory network have been identified.
      However, most of them are transcription factors. Long noncoding RNAs (lncRNAs)
      emerged as common players acting on epigenetic or transcriptional regulation in
      several eukaryotic organisms. To date, no lncRNA has been described in
      filamentous fungi. Results: A lncRNA termed HAX1 was identified in T. reesei
      QM9414. In this study, it was characterized and evidence for its regulatory
      impact on cellulase expression was provided. Interestingly, different versions of
      HAX1 were identified in different strains (namely, QM6a, QM9414, and Rut-C30),
      varying in terms of RNA length. Remarkably, considerable longer variants of this
      lncRNA are present in hypercellulolytic strains compared to the wild-type strain
      QM6a. Based on these results, a correlation between RNA length and the functional
      impact of HAX1 on PBDE expression was supposed. This assumption was verified by
      overexpressing the most abundant HAX1 versions identified in QM6a, QM9414, and
      Rut-C30. Such HAX1 overexpression on the one hand was suitable for regaining the
      function in hax1 disruption strains, and on the other hand resulted in notably
      higher cellulase activities in QM6a, especially by the expression of longer HAX1
      versions. Conclusion: With HAX1, for the first time the regulatory role of a
      lncRNA in filamentous fungi was uncovered. Besides this, a new player involved in
      the complex regulation of PBDE expression in T. reesei was identified. Due to its
      enhancing effect on cellulase activity, HAX1 was shown to be not only interesting
      for basic research, but also a promising candidate for expanding the set of
      biotechnological tools for industrial application of T. reesei.

PMID- 29588664
TI  - A fast and sensitive activity assay for lytic polysaccharide monooxygenase.
AB  - Background: Lytic polysaccharide monooxygenases (LPMO) release a spectrum of
      cleavage products from their polymeric substrates cellulose, hemicellulose, or
      chitin. The correct identification and quantitation of these released products is
      the basis of MS/HPLC-based detection methods for LPMO activity. The duration,
      effort, and intricate analysis allow only specialized laboratories to measure
      LPMO activity in day-to-day work. A spectrophotometric assay will simplify the
      screening for LPMO in culture supernatants, help monitor recombinant LPMO
      expression and purification, and support enzyme characterization. Results: Based
      on a newly discovered peroxidase activity of LPMO, we propose a fast, robust, and
      sensitive spectrophotometric activity assay using 2,6-dimethoxyphenol (2,6-DMP)
      and H2O2. The fast enzymatic assay (300 s) consists of 1 mM 2,6-DMP as
      chromogenic substrate, 100 uM H2O2 as cosubstrate, and an adequate activity of
      LPMO in a suitable buffer. The high molar absorption coefficient of the formed
      product coerulignone (epsilon469 = 53,200 M-1 cm-1) makes the assay sensitive and
      allows reliable activity measurements of LPMO in concentrations of approx. 0.5-50
      mg L-1. Conclusions: The activity assay based on 2,6-DMP detects a novel
      peroxidase activity of LPMO. This activity can be accurately measured and used
      for enzyme screening, production, and purification, and can also be applied to
      study binding constants or thermal stability. However, the assay has to be used
      with care in crude extracts, because other enzymes such as laccase or peroxidase
      will interfere with the assay. We also want to stress that the peroxidase
      activity is a homogeneous reaction with soluble substrates and should not be
      correlated to heterogeneous LPMO activity on polymeric substrates.

PMID- 29588666
TI  - Foreword.

PMID- 29588665
TI  - The diversity and specificity of the extracellular proteome in the cellulolytic
      bacterium Caldicellulosiruptor bescii is driven by the nature of the cellulosic
      growth substrate.
AB  - Background: Caldicellulosiruptor bescii is a thermophilic cellulolytic bacterium
      that efficiently deconstructs lignocellulosic biomass into sugars, which
      subsequently can be fermented into alcohols, such as ethanol, and other products.
      Deconstruction of complex substrates by C. bescii involves a myriad of highly
      abundant, substrate-specific extracellular solute binding proteins (ESBPs) and
      carbohydrate-active enzymes (CAZymes) containing carbohydrate-binding modules
      (CBMs). Mass spectrometry-based proteomics was employed to investigate how these
      substrate recognition proteins and enzymes vary as a function of lignocellulosic
      substrates. Results: Proteomic analysis revealed several key extracellular
      proteins that respond specifically to either C5 or C6 mono- and polysaccharides.
      These include proteins of unknown functions (PUFs), ESBPs, and CAZymes. ESBPs
      that were previously shown to interact more efficiently with hemicellulose and
      pectin were detected in high abundance during growth on complex C5 substrates,
      such as switchgrass and xylan. Some proteins, such as Athe_0614 and Athe_2368,
      whose functions are not well defined were predicted to be involved in xylan
      utilization and ABC transport and were significantly more abundant in complex and
      C5 substrates, respectively. The proteins encoded by the entire glucan
      degradation locus (GDL; Athe_1857, 1859, 1860, 1865, 1867, and 1866) were highly
      abundant under all growth conditions, particularly when C. bescii was grown on
      cellobiose, switchgrass, or xylan. In contrast, the glycoside hydrolases
      Athe_0609 (Pullulanase) and 0610, which both possess CBM20 and a starch binding
      domain, appear preferential to C5/complex substrate deconstruction. Some PUFs,
      such as Athe_2463 and 2464, were detected as highly abundant when grown on C5
      substrates (xylan and xylose), also suggesting C5-substrate specificity.
      Conclusions: This study reveals the protein membership of the C. bescii secretome
      and demonstrates its plasticity based on the complexity (mono-/disaccharides vs.
      polysaccharides) and type of carbon (C5 vs. C6) available to the microorganism.
      The presence or increased abundance of extracellular proteins as a response to
      specific substrates helps to further elucidate C. bescii's utilization and
      conversion of lignocellulosic biomass to biofuel and other valuable products.
      This includes improved characterization of extracellular proteins that lack
      discrete functional roles and are poorly/not annotated.

PMID- 29588667
TI  - Intravascular Ultrasound Versus Optical Coherence Tomography for Coronary Artery
      Imaging - Apples and Oranges?
AB  - Intravascular imaging has advanced our understanding of coronary artery disease
      and facilitated decision-making in percutaneous coronary intervention (PCI). In
      particular, intravascular ultrasound (IVUS) has contributed significantly to
      modern PCI techniques. The recent introduction of optical coherence tomography
      (OCT) has further expanded this field due to its higher resolution and rapid
      image acquisition as compared with IVUS. Furthermore, OCT allows detailed
      planning of interventional strategies and optimisation before stent deployment,
      particularly with complex lesions. However, to date it is unclear whether OCT is
      superior to IVUS as an intracoronary imaging modality with limited data
      supporting OCT use in routine clinical practice. This review aims to compare
      these two intracoronary imaging techniques and the recent evidence for their use
      in this ever-changing field within interventional cardiology.

PMID- 29588668
TI  - Percutaneous Coronary Intervention in Patients Who Have an Indication for Oral
      Anticoagulation - an Evidence-based Approach to Antithrombotic Therapy.
AB  - Dual antiplatelet therapy (DAPT) is required following percutaneous coronary
      intervention (PCI) to prevent stent thrombosis. The optimal antithrombotic
      therapy following PCI for patients with an indication for long-term oral
      anticoagulation (OAC) is uncertain. DAPT and OAC, a combination known as 'triple
      therapy', reduces cardiovascular event rates but is associated with a substantial
      risk of bleeding. Recent data suggest that the duration of DAPT (and thereby
      triple therapy in those who also require OAC) can be limited to 1-3 months
      following new-generation drug-eluting stent deployment, and that aspirin may be
      omitted from triple therapy, without increasing the rate of ischaemic
      cardiovascular events. The increasing use of non-vitamin K antagonist oral
      anticoagulants and new antiplatelet agents (prasugrel and ticagrelor) has further
      complicated antithrombotic prescribing. This article aims to provide a summary of
      the evidence regarding antithrombotic therapy after PCI in patients who have an
      indication for OAC and to provide a framework to aid clinical decision-making in
      this area.

PMID- 29588669
TI  - Major Bleeding and Adverse Outcome following Percutaneous Coronary Intervention.
AB  - Advances in anti-thrombotic and anti-platelet therapies have improved outcomes in
      patients undergoing percutaneous coronary interventions (PCIs) through a
      reduction in ischaemic events, at the expense of peri-procedural bleeding
      complications. These may occur through either the access site through which the
      PCI was performed or through non-access-related sites. There are currently over
      10 definitions of major bleeding events consisting of clinical events, changes in
      laboratory parameters and clinical outcomes, where different definitions will
      differentially influence the reported incidence of major bleeding events. Use of
      different major bleeding definitions has been shown to change the reported
      outcome of a number of therapeutic strategies in randomised controlled trials but
      as yet a universal bleeding definition has not gained widespread adoption in
      assessing the efficacy of such therapeutic interventions. Major bleeding
      complications are independently associated with adverse mortality and major
      adverse cardiovascular event (MACE) outcomes, irrespective of the definition of
      major bleeding used, with the worst outcomes associate with non-access-site
      related bleeds. We consider the mechanisms through which bleeding complications
      may affect longer-term outcomes and discuss bleeding avoidance strategies,
      including access site choice, pharmacological considerations and formal bleeding
      risk assessment to minimise such bleeding events.

PMID- 29588670
TI  - Contemporary Antiplatelet Strategies in the Treatment of STEMI using Primary
      Percutaneous Coronary Intervention.
AB  - Reperfusion therapy for patients presenting with an acute ST-segment elevation
      myocardial infarction (STEMI) involves primary percutaneous coronary intervention
      (PPCI) and concomitant oral antiplatelet and intravenous antithrombotic
      pharmacotherapy. There is a conflict between the desire to reduce the time
      between first medical contact and coronary re-canalisation and achieving
      effective platelet inhibition with oral antiplatelet agents. This review outlines
      the currently available antiplatelet treatments, and their place within the
      therapeutic timeline of a patient presenting with STEMI. Additionally, we focus
      on current challenges associated with effective antiplatelet treatment, including
      acute stent thrombosis (AST), the effect of morphine, platelet function
      assessment and concomitant anticoagulant therapy.

PMID- 29588671
TI  - Preventive Percutaneous Coronary Intervention in ST-elevation Myocardial
      Infarction - The Primacy of Randomised Trials.
AB  - Randomised trials show a benefit of preventive (non-infarct artery) percutaneous
      coronary intervention in patients with acute ST elevation myocardial infarction,
      but non-randomised studies do not. The evidence on each is quantified and
      assessed. The primacy of randomised trials reveals the danger of using non
      randomised studies that can, as in this case, give the wrong answer.

PMID- 29588672
TI  - Interventional Strategies in Thrombus Management for ST Elevation Myocardial
      Infarction.
AB  - The major limitation of modern primary percutaneous coronary intervention (PPCI)
      is distal embolisation of thrombus and microvascular obstruction. Microvascular
      flow, as measured by myocardial blush grade (MPG), predicts mortality after PPCI.
      Despite initial enthusiasm, current evidence does not support routine use of
      Intracoronary over intravenous glycoprotein 2b3a inhibitors during PPCI for ST
      elevation myocardial infarction (STEMI) to improve clinical outcomes. Manual
      thrombectomy (MT) improves MPG and reduces distal embolisation in meta-analyses
      of small trials. A single-centre trial (N=1071), the Thrombus aspiration during
      percutaneous coronary intervention in acute myocardial infarction study (TAPAS)
      trial showed a mortality reduction, which led guidelines to recommend routine
      manual aspiration. However, the largest randomised trial (Thrombus aspiration in
      ST-elevation myocardial infarction in Scandinavia [TASTE] trial, N=7021) showed
      no difference in mortality and only trends towards reduction in myocardial
      infarction (MI) and stent thrombosis. The TASTE trial had much lower than
      expected mortality and so was likely underpowered for modest but important
      treatment effects (20-30 % RRR). The Thrombectomy with PCI versus PCI alone in
      patients with STEMI undergoing primary PCI (TOTAL) trial (N=10,700) will
      determine if MT reduces important clinical events during PPCI. Thrombus
      management remains an important area of research in STEMI.

PMID- 29588674
TI  - Transcatheter Aortic Valve Replacement for Native Aortic Valve Regurgitation.
AB  - Transcatheter aortic valve replacement with either the balloon-expandable Edwards
      SAPIEN XT valve, or the self-expandable CoreValve prosthesis has become the
      established therapeutic modality for severe aortic valve stenosis in patients who
      are not deemed suitable for surgical intervention due to excessively high
      operative risk. Native aortic valve regurgitation, defined as primary aortic
      incompetence not associated with aortic stenosis or failed valve replacement, on
      the other hand, is still considered a relative contraindication for transcatheter
      aortic valve therapies, because of the absence of annular or leaflet
      calcification required for secure anchoring of the transcatheter heart valve. In
      addition, severe aortic regurgitation often coexists with aortic root or
      ascending aorta dilatation, the treatment of which mandates operative
      intervention. For these reasons, transcatheter aortic valve replacement has been
      only sporadically used to treat pure aortic incompetence, typically on a
      compassionate basis and in surgically inoperable patients. More recently,
      however, transcatheter aortic valve replacement for native aortic valve
      regurgitation has been trialled with newer-generation heart valves, with
      encouraging results, and new ancillary devices have emerged that are designed to
      stabilize the annulus-root complex. In this paper we review the clinical context,
      technical characteristics and outcomes associated with transcatheter treatment of
      native aortic valve regurgitation.

PMID- 29588673
TI  - The Role of Percutaneous Haemodynamic Support in High-risk Percutaneous Coronary
      Intervention and Cardiogenic Shock.
AB  - The experience and usage of percutaneous cardiac assist devices in cardiogenic
      shock as well as high-risk percutaneous coronary intervention have increased over
      the years. Nonetheless, there is still little evidence of clinical benefit of
      these devices other than immediate haemodynamic improvement. Despite the fact
      that these devices are used to treat a rather complex patient population,
      clinical testing remains important in order to evaluate their true impact on
      clinical outcome before being adopted into clinical practice. Therefore, this
      review shows an overview of the current experience and evidence of the available
      percutaneous cardiac assist devices.

PMID- 29588675
TI  - The Current Situation and the Future of Emergent Cardiac Surgery in TAVI.
AB  - Transcatheter aortic valve implantation (TAVI) has become a beneficial treatment
      for patients with aortic valve stenosis deemed at high or even prohibitive risk
      for open surgery. The risk for severe complications is low (ranging between 0.2 %
      and 1.0 %); nevertheless, in approximately 1 % of patients emergency cardiac
      surgery (ECS) is required during TAVI. Aortic injury, embolization of the TAVI
      prosthesis, and myocardial injury are among the most frequent complications
      necessitating ECS. Mortality rates of ECS during TAVI are high, ranging between
      45 % and 67 %, owing to the comorbid and fragile health status of TAVI patients.
      Therefore, avoidance of complications appears to be of utmost importance to
      improve outcomes. This review analysis the current literature in terms of
      incidence, causes, and outcomes of ECS during TAVI.

PMID- 29588676
TI  - Indications for Surgery for Tricuspid Regurgitation.
AB  - Despite the fact that tricuspid regurgitation (TR) can result in significant
      symptoms, patients are rarely referred for isolated surgical repair, or
      replacement, and most surgeries are performed in the context of other planned
      cardiac surgery. In this article, we review the different causes of TR, the
      natural history of untreated severe TR, indications and timing for isolated TR
      surgery, indications for TR surgery performed at the time of left-sided valve
      surgery, and surgical approaches for correction of TR.

PMID- 29588677
TI  - Foreword.

PMID- 29588678
TI  - Is Hyperaemia Essential for Accurate Functional Assessment of Coronary Stenosis
      Severity?
AB  - Fractional flow reserve (FFR) requires the use of maximal hyperaemia as described
      in the original preclinical and clinical validation studies and subsequent
      practice changing randomized controlled trials. A perception that the need for
      hyperaemia (usually induced with adenosine) was one of the obstacles to more
      widespread adoption of FFR has led to interest in the use of resting non
      hyperaemic indices to assess the functional significance of coronary stenoses. We
      examine the current evidence base and conclude that resting indices agree with
      FFR in only 80 % of lesions when a binary cut-off is employed but closer to 90 %
      when hybrid strategies utilising both resting indices and FFR are utilised. It
      seems counter intuitive to sacrifice diagnostic accuracy when in most patients
      and healthcare systems the induction of hyperaemia with adenosine is safe and
      emminently affordable.

PMID- 29588679
TI  - Integrating Physiology into the DNA of Coronary Revascularisation - A Historical
      Perspective, Contemporary Review and Blueprint for the Future of Coronary
      Physiology.
AB  - The clinical and economic benefits of physiologically guided revascularisation
      have been demonstrated, yet its clinical adoption remains unacceptably low.
      Recently, new indices of stenosis severity have been introduced that aim to
      improve adoption by circumventing the limitations of existing indices. The most
      validated of these new indices is the instantaneous wave-free ratio (iFR). This
      review will describe the physiological basis of this index, how it avoids the
      problems of existing indices such as fractional flow reserve (FFR) and the
      clinical validation studies of iFR to date. We will then describe a novel use of
      iFR, which has the potential to transform the use of physiology in the catheter
      lab and finally integrate physiology into the DNA of coronary revascularisation.

PMID- 29588680
TI  - AXXESSTM Stent: Delivery Indications and Outcomes.
AB  - The successful treatment of coronary bifurcation lesions remains one of the
      challenges of interventional cardiology. The current consensus of the European
      Bifurcation Club based on published data advocates a provisional strategy,
      treating the main vessel (MV) with a single stent covering the side branch (SB),
      with bailout SB stenting as required. The success of this approach may be limited
      by failure to attain SB access after MV stenting but is preferred in most
      situations over routine SB plus MV stent techniques, which are associated with a
      significant increase in the rate of major adverse cardiac events. The AXXESS self
      expanding biolimus-eluting stent has been developed as a solution to these
      challenges within the coronary circulation and maintains provisional MV stent
      approach but with added assurance of maintained SB access. It has a unique
      conical structure that is positioned spanning the carina, with scaffold extending
      into the carina of both the MV and SB. The purpose of this article is to describe
      the indication, implantation technique and outcome data supporting the use of the
      AXXESS stent in the treatment of coronary bifurcation lesions.

PMID- 29588681
TI  - Vascular Access and Chronic Total Occlusion Angioplasty.
AB  - The hybrid algorithim approach, together with innovative new technologies, has
      lead to increased interest in chronic total occlusion (CTO) percutaneous coronary
      intervention (PCI) and increasing procedural success rates. Unlike non-CTO PCI,
      there is an increased rate of femoral access. When considering arterial access in
      CTO PCI, a balance is needed between anticipated procedural difficulty, planned
      CTO strategy and the desire to minimise the risk of vascular access-related
      complications. We review the evidence for best practice with respect to femoral
      puncture technique and also assess the technologies and techniques available to
      place larger inner diameter catheters into the radial artery.

PMID- 29588682
TI  - Avoiding Coronary Occlusion and Root Rupture in TAVI - The Role of Pre-procedural
      Imaging and Prosthesis Selection.
AB  - Coronary occlusion and rupture of the aortic root or annulus remain two major
      concerns of transcatheter aortic valve implantation technique. Despite their
      relatively low frequency they raised the interest of the scientific community as
      they carry an extremely poor prognosis. Prosthesis type and size selection is
      part of the patient selection process that allows the operator to prevent these
      complications. In this article, the techniques used either during pre-TAVI
      screening or during the procedure itself to avoid coronary occlusion and aortic
      rupture will be discussed.

PMID- 29588683
TI  - Permanent Pacemaker Implantation after TAVR - Predictors and Impact on Outcomes.
AB  - The number of patients undergoing transcatheter aortic valve replacement (TAVR)
      worldwide is increasing steadily. Atrioventricular conduction disturbances, with
      or without the need for permanent pacemaker (PPM) implantation, are one of the
      most common adverse events after TAVR. Among transcatheter heart valves (THV),
      rates of conduction abnormalities vary from less than 10 % to more than 50 %.
      Depending on the reported data referred to, historical data showed that up to one
      third of the patients required implantation of a PPM following TAVR. Although
      generally considered as a minor complication, PPM may have a profound impact on
      prognosis and quality of life after TAVR. Current data support the hypothesis
      that conduction abnormalities leading to pacemaker dependency result from
      mechanical compression of the conduction system by the prosthesis stent frame and
      individual predisposing conduction defects such as right bundle-branch block
      (RBBB). With several large randomised trials and registry studies having been
      published recently and second generation THV having been introduced, the debate
      about predictors for pacemaker implantation and their impact on outcome after
      TAVR is still ongoing.

PMID- 29588684
TI  - Balloon- or Self-Expandable TAVI: Clinical Equipoise?
AB  - Transcatheter aortic valve implantation (TAVI) has become an effective treatment
      option for patients with severe aortic stenosis and high surgical risk or
      contraindications for surgical aortic valve replacement. Most of the currently
      available prostheses employ either balloon-expandable or self-expandable designs.
      Presently, there is a paucity of data directly comparing these two widely used
      prosthesis types. Forthcoming trials will reveal whether newer designs of both
      technologies translate into fewer complications and better outcomes, with
      expansion of TAVI indications. This manuscript reviews features and clinical
      outcomes of balloon- and self-expanding prostheses, summarising current data from
      registries and trials.

PMID- 29588685
TI  - Real World Outcomes of Left Atrial Appendage Occlusion.
AB  - Percutaneous left atrial appendage occlusion (LAAO) is a device-based therapy for
      the prevention of stroke in patients with non-valvular atrial fibrillation (AF).
      Recently, the Watchman device (Boston Scientific, St Paul, MN, US) was approved
      in the US by the Food and Drug Administration (FDA) based on the results of two
      randomised clinical trials that evaluated LAAO in patients eligible for oral
      anticoagulation (OAC) therapy. However, in real-word clinical practice LAAO is
      typically offered to patients ineligible for OAC therapy, as they appear to have
      limited treatment options and consequently worse prognosis. Although LAAO has
      shown favourable clinical outcomes in OAC-ineligible patients in single or
      multicentre observational studies, these results need to be confirmed in
      randomised clinical trials.

PMID- 29588686
TI  - A Quick Guide to Paravalvular Leak Closure.
AB  - Paravalvular leak (PVL) is a seldomly covered aspect of structural heart disease.
      However, this is a condition that frequently presents after valvular replacement.
      This article will cover the diagnosising and treating PVL (i.e. imaging, access,
      and device selection). In addition, specific aspects of aortic and mitral PVL
      closure will be covered in this review.

PMID- 29588687
TI  - Foreword.

PMID- 29588688
TI  - Left Main Stem Percutaneous Coronary Intervention - Data and Ongoing Trials.
AB  - Left main stem (LMS) disease is associated with significant morbidity and
      mortality. Traditionally coronary artery bypass grafting (CABG) has been the gold
      standard for treatment of these lesions. However over the past decade,
      percutaneous coronary intervention (PCI) has assumed a more prominent role in the
      treatment of LMS disease. With the advent of newer drug-eluting stents (DES) with
      an improved risk factor profile, better intravascular imaging modalities and
      careful patient selection, the use of PCI in this cohort is expanding. We review
      the current data to support this and discuss the on-going trials that will
      hopefully shed more light into the management of this complex disease.

PMID- 29588689
TI  - Twelve Months Dual Antiplatelet Therapy after Drug-eluting Stents - Too Long, too
      Short or Just Right?
AB  - Dual Antiplatelet Therapy (DAPT) remains a cornerstone in the secondary
      prevention of coronary artery disease. Further, in contemporary practice, a
      period of DAPT is considered a mandatory requirement after intracoronary stents
      to prevent stent thrombosis (ST), a complication associated with heart attack and
      a mortality rate of up to 40 %. In current clinical practice, the default
      strategy in most centres is 12 months' DAPT followed by aspirin alone for life.
      However, the optimal duration of DAPT, particularly given the rapid iterative
      turnover of drug-eluting stents (DES) is the subject of discrepant evidence and
      clinical uncertainty. In particular, the 12-month regimen is based upon
      relatively weak evidence. A series of fairly small randomised trials, not powered
      to look specifically at ST as an endpoint, have recently indicated that there is
      no apparent disadvantage to shorter versus longer duration DAPT (including
      several trials of >12 months versus 12 months) when looking at various composite
      clinical endpoints. By contrast, the 9,961 patient DAPT trial, published in the
      New England Journal of Medicine at the end of 2014, demonstrated clinical outcome
      benefit, including a significantly lower rate of ST as a predefined primary
      endpoint, in DES patients randomised to 30 months' DAPT compared to stopping at
      12 months. Here, the authors to assess the data, including the most recent meta
      analyses, in an attempt to answer the question: DAPT after DES...12 months,
      longer or shorter?

PMID- 29588690
TI  - Managing the Antithrombotic Therapy After Percutaneous Coronary Intervention in
      Patients on Oral Anticoagulation.
AB  - In patients on chronic oral anticoagulation (OAC) who are undergoing a
      percutaneous coronary intervention (PCI), dual antiplatelet therapy (aspirin and
      a P2Y12 inhibitor) is required. However, combining dual antiplatelet therapy with
      OAC increases the risk of bleeding. Newer and stronger P2Y12 inhibitors also add
      more complexity to the regimen, as these antiplatelet agents are currently
      recommended as standard treatment in patients with acute coronary syndromes
      (ACS). It remains unclear whether these ACS patients on chronic OAC undergoing
      PCI should be treated with these new P2Y12 inhibitors as part of the antiplatelet
      therapy. Another issue to address is that new non-vitamin K oral anticoagulants
      have emerged as possible alternatives for stroke prevention in patients with AF.
      Thus, the anticoagulated patient undergoing PCI faces a treatment dilemma. Based
      on a real-life case, we will discuss the optimal anticoagulant and antiplatelet
      treatment with a review of the literature.

PMID- 29588691
TI  - Spontaneous Coronary Artery Dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non
      iatrogenic separation of the coronary artery wall that is now recognised as an
      important cause of myocardial infarction, especially in younger women. SCAD can
      be elusive on coronary angiography and clinician familiarity with non
      pathognomonic angiographic SCAD variants and the use of intracoronary imaging
      will improve diagnosis. Conservative management and long-term cardiovascular
      follow-up are typically recommended.

PMID- 29588692
TI  - Review of Minimally Invasive Aortic Valve Surgery.
AB  - Minimally invasive aortic valve surgery (MIAVS) has been developed for the last
      20 years. The improvements in techniques have permitted cardiac surgeons to
      perform aortic valve replacement safely and efficiently with minimally incisions.
      Patients have become older and have multiple comorbidities and this is expected
      to grow in number. Less-invasive procedures are known to reduce the number of
      complications, together with smaller incisions, less pain, less blood loss and
      reduced length of hospital stay. Selective preoperative planning with computed
      tomography is key to the pre-investigation stage. Hybrid and staged procedures
      with interventional cardiologists are part of the armamentarium and may be
      appealing for the present and near future. Despite the nature of demanding
      procedures and longer learning curve with increased cardiopulmonary bypass times,
      the outcomes are comparable with same quality as conventional open surgery.
      Patient recovery is the ultimate purpose of these approaches.

PMID- 29588694
TI  - Transcatheter Aortic Valve Implantation for Patients with Smaller Anatomy.
AB  - Transcatheter aortic valve implantation (TAVI) has reached relative maturity for
      the treatment of severe, symptomatic aortic stenosis (AS). TAVI for patients with
      smaller anatomy is a challenging procedure due to specific anatomical difficulty
      and complications including annulus rupture and vascular complications.
      Prevention of these complications, and the introduction of a newer-generation and
      lower-profile TAVI system, will encourage the prevalence of TAVI for patients
      with smaller anatomy.

PMID- 29588693
TI  - Computed Tomography for Structural Heart Disease and Interventions.
AB  - Transcatheter cardiac interventions are a fast evolving field. The past decade
      has seen the development of transcatheter aortic valve replacement, transcatheter
      mitral valve repair and replacement, septal defect closure devices and left
      atrial appendage closure devices for thromboprophylaxis. More than ever, medical
      imaging is taking a central role in the care of patients with structural heart
      disease. In this review article we outline the use of MSCT as a tool for
      diagnosis of structural heart interventions, as well as patient selection, pre
      procedural planning, device sizing and post-procedural assessment. We focus on
      procedures targeting the aortic valve, the mitral valve, the inter-atrial septum
      and the left atrial appendage.

PMID- 29588695
TI  - Patient-tailored Drug-eluting Stent Choice - A Solution for Patients with
      Diabetes: Proceedings of Two Satellite Symposia Held at EuroPCR in May 2015 in
      Paris.
AB  - Although second-generation drug-eluting stents (DES) have improved outcomes in
      percutaneous coronary interventions (PCIs), important unmet needs remain. Two
      symposia at EuroPCR 2015 focused on two challenging scenarios. First, patients
      with diabetes mellitus (DM) have generally inferior outcomes following PCI. The
      Cre8TM stent (manufactured by CID Spa, member of Alvimedica Group) has shown
      unique efficacy in subpopulations of patients with DM during clinical trials. A
      live case in a patient with diabetes illustrated the challenges of complex
      multivessel disease. Second, optimising stent selection towards devices that have
      demonstrated complete and early endothelialisation offers the potential to reduce
      the duration of dual antiplatelet therapy. The Cre8TM DES features a polymer-free
      platform and has been associated with low rates of in-stent thrombosis.

PMID- 29588696
TI  - Absorbable Polymer Technology - Viable Solutions for Unmet Needs in PCI:
      Proceedings of two satellite symposia held at EuroPCR, Paris in May 2015.
AB  - The use of drug-eluting stents (DES) has improved clinical outcomes in
      percutaneous coronary intervention procedures, but many challenges remain. In two
      symposia at EuroPCR 2015, the factors necessary to ensure successful chronic
      total occlusion (CTO) intervention were presented. Good preparation, sufficient
      operator experience and the correct approach are key to the success of CTO
      interventions. A live case demonstrated the challenges of these complex cases.
      Stent choice in CTO interventions is crucial; second-generation DES are
      associated with lower rates of restenosis and re-occlusion compared with first
      generation DES. The CoractoTM DES features unique structural properties and
      rapidly absorbable polymer, resulting in excellent conformability, efficacy and
      safety.

PMID- 29588697
TI  - Foreword.

PMID- 29588698
TI  - Editorial From the Coronary Section Editor.

PMID- 29588699
TI  - Choice of Intracoronary Imaging: When to use Intravascular Ultrasound or Optical
      Coherence Tomography.
AB  - Intracoronary imaging has the capability of accurately measuring vessel and
      stenosis dimensions, assessing vessel integrity, characterising lesion morphology
      and guiding optimal percutaneous coronary intervention (PCI). Coronary
      angiography used to detect and assess coronary stenosis severity has limitations.
      The 2D nature of fluoroscopic imaging provides lumen profile only and the
      assessment of coronary stenosis by visual estimation is subjective and prone to
      error. Performing PCI based on coronary angiography alone is inadequate for
      determining key metrics of the vessel such as dimension, extent of disease, and
      plaque distribution and composition. The advent of intracoronary imaging has
      offset the limitations of angiography and has shifted the paradigm to allow a
      detailed, objective appreciation of disease extent and morphology, vessel
      diameter, stent size and deployment and healing after PCI. It has become an
      essential tool in complex PCI, including rotational atherectomy, in follow-up of
      novel drug-eluting stent platforms and understanding the pathophysiology of stent
      failure after PCI (e.g. following stent thrombosis or in-stent restenosis). In
      this review we look at the two currently available and commonly used
      intracoronary imaging tools - intravascular ultrasound and optical coherence
      tomography - and the merits of each.

PMID- 29588701
TI  - Coronary Intervention with the Excimer Laser: Review of the Technology and
      Outcome Data.
AB  - Excimer laser coronary atherectomy (ELCA) is a long-established adjunctive
      therapy that can be applied during percutaneous coronary intervention (PCI).
      Technical aspects have evolved and there is an established safety and efficacy
      record across a number of clinical indications in contemporary interventional
      practice where complex lesions are routinely encountered. The role of ELCA during
      PCI for thrombus, non-crossable or non-expandable lesions, chronic occlusions and
      stent under-expansion are discussed in this review. The key advantage of ELCA
      over alternative atherectomy interventions is delivery on a standard 0.014-inch
      guidewire. Additionally, the technique can be mastered by any operator after a
      short period of training. The major limitation is presence of heavy calcification
      although when rotational atherectomy (RA) is required but cannot be applied due
      to inability to deliver the dedicated RotaWireTM (Boston Scientific), ELCA can
      create an upstream channel to permit RotaWire passage and complete the case with
      RA - the RASER technique.

PMID- 29588700
TI  - Fractional Flow Reserve: Does a Cut-off Value add Value?
AB  - Fractional flow reserve (FFR) has been shown to improve outcomes when used to
      guide percutaneous coronary intervention (PCI). There have been two proposed cut
      off points for FFR. The first was derived by comparing FFR against a series of
      non-invasive tests, with a value of <=0.75 shown to predict a positive ischaemia
      test. It was then shown in the DEFER study that a vessel FFR value of >=0.75 was
      associated with safe deferral of PCI. During the validation phase, a 'grey zone'
      for FFR values of between 0.76 and 0.80 was demonstrated, where a positive non
      invasive test may still occur, but sensitivity and specificity were sub-optimal.
      Clinical judgement was therefore advised for values in this range. The FAME
      studies then moved the FFR cut-off point to <=0.80, with a view to predicting
      outcomes. The <=0.80 cut-off point has been adopted into clinical practice
      guidelines, whereas the lower value of <=0.75 is no longer widely used. Here, the
      authors discuss the data underpinning these cut-off values and the practical
      implications for their use when using FFR guidance in PCI.

PMID- 29588702
TI  - Patient Selection and Procedural Considerations for Coronary Orbital Atherectomy
      System.
AB  - Despite advances in technology, percutaneous coronary intervention (PCI) of
      severely calcified coronary lesions remains challenging. Rotational atherectomy
      is one of the current therapeutic options to manage calcified lesions, but has a
      limited role in facilitating the dilation or stenting of lesions that cannot be
      crossed or expanded with other PCI techniques due to unfavourable clinical
      outcome in long-term follow-up. However the results of orbital atherectomy
      presented in the ORBIT I and ORBIT II trials were encouraging. In addition to
      these encouraging data, necessity for sufficient lesion preparation before
      implantation of bioresorbable scaffolds lead to resurgence in the use of
      atherectomy. This article summarises currently available publications on orbital
      atherectomy (Cardiovascular Systems Inc.) and compares them with rotational
      atherectomy.

PMID- 29588703
TI  - Primary Angioplasty For Patients in Cardiogenic Shock: Optimal Management.
AB  - Cardiogenic shock complicates approximately 5-10 % of all MI events and remains
      the most common cause of death among MI cases. Over the past few decades, the
      mortality rate associated with cardiogenic shock has decreased with the
      introduction of early revascularisation, although there are limited data for
      patients with triple-vessel disease and left main stem disease. In more recent
      years, there have been a number of advances in the mechanical circulatory support
      devices that can help improve the haemodynamics of patients in cardiogenic shock.
      Despite these advances, together with progress in the use of inotropes and
      vasopressors, cardiogenic shock remains associated with high morbidity and
      mortality rates. This review will outline the management of cardiogenic shock
      complicating acute MI with a smajor focus on revascularisation techniques and the
      use of mechanical circulatory support devices.

PMID- 29588704
TI  - Determining the Most Appropriate Mode of Coronary Artery Revascularisation in
      Patients With Diabetes.
AB  - Obstructive coronary artery disease is a common cause of morbidity and mortality
      among patients with diabetes mellitus (DM). Previous research has demonstrated
      that the clinical sequelae of coronary artery disease remains the most common
      cause of death in this population. As a result numerous observational studies and
      randomised clinical trials have evaluated the timing and mode of coronary artery
      revascularisation within this population. In this review, we survey the currently
      available data informing the indications and optimal method of coronary
      revascularisation for diabetic patients.

PMID- 29588705
TI  - The use of the Cre8 Stent in Patients With Diabetes Mellitus.
AB  - Despite improved clinical outcomes following the availability of second
      generation drug eluting stents (DES), percutaneous coronary intervention (PCI) is
      associated with worse clinical and angiographic outcomes among patients with
      diabetes mellitus (DM) than among non-diabetics. The Cre8TM Amphilimus-eluting
      DES is polymer-free, resulting in a reduced inflammatory response and lower risk
      of stent thrombosis. It showed equivalent efficacy and safety in diabetic and non
      diabetic populations, a unique finding among DES studies. These findings were
      confirmed in a real-world study called INVESTIG8. Another real-world study,
      pARTicip8, is ongoing. The RESERVOIR clinical trial recruited patients with
      diabetes mellitus and showed noninferiority of the Cre8 DES compared to an
      everolimus-eluting DES but showed a statistical superiority of Cre8 in diabetic
      patients with higher metabolic dysfunctions. The Cre8 DES is therefore a valuable
      option for this important patient population.

PMID- 29588706
TI  - Dual Antiplatelet Therapy After Drug-eluting Stent Implantation.
AB  - The current guidelines for percutaneous coronary intervention use recommend dual
      antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor after drug eluting
      stent (DES) implantation. The optimal duration of DAPT is however area of debate.
      Recent clinical trials and meta-analyses suggest that the choice of DAPT duration
      should be tailored individually, based on the balance between ischemic and
      bleeding risk carried by the patient.

PMID- 29588707
TI  - Impact of Mitral Regurgitation on Clinical Outcomes After Transcatheter Aortic
      Valve Implantation.
AB  - Severe aortic stenosis (AS) and mitral regurgitation (MR) are the two most common
      valvular lesions referred for surgical intervention in Europe and frequently co
      exist. In patients with both severe AS and significant MR referred for surgical
      aortic valve replacement (SAVR), a concomitant mitral valve intervention is
      typically performed if the MR is severe, despite the higher associated
      perioperative risk. The management of moderate MR among SAVR patients is
      controversial and depends on a number of factors including MR aetiology (i.e.,
      organic versus functional MR), feasibility of repair and patient risk profile.
      Moderate or severe MR is present in up to one-third of patients undergoing
      transcatheter aortic valve implantation (TAVI), is mainly of functional aetiology
      and is typically left untreated. Although data are conflicting, a growing body of
      evidence suggests that significant MR exerts an adverse effect on both short- and
      long-term clinical outcomes after TAVI. Moderate or severe MR improves in just
      over half of patients following TAVI and recent data suggest MR is more likely to
      improve among patients receiving a balloon-expandable as compared with a self
      expandable transcatheter heart valve.

PMID- 29588708
TI  - Hybrid Imaging in the Catheter Laboratory: Real-time Fusion of Echocardiography
      and Fluoroscopy During Percutaneous Structural Heart Disease Interventions.
AB  - Percutaneous catheter-based techniques for the treatment of structural heart
      disease are becoming more complex, and current imaging techniques have
      limitations: while fluoroscopy gives poor visualisation of cardiac anatomical
      structures, echocardiography is limited in its ability to detect the position of
      catheters and devices. The EchoNavigator(r) (Philips) live image guidance tool is
      a novel system that integrates real-time echocardiography with fluoroscopic X-ray
      imaging, optimising the guidance and positioning of devices. Use of the
      EchoNavigator system facilitates improved understanding of anatomical structures
      while showing enhanced visualisation of catheter and device movements. Early
      clinical experience suggests that the technology is feasible and safe, and
      provides enhanced understanding of the relationship between soft tissue anatomy
      and catheter devices in structural heart disease. The use of the EchoNavigator
      system can improve the confidence of interventional cardiologists in the
      targeting and positioning of devices in percutaneous interventions in structural
      heart disease, and has the potential to reduce procedural time, reduce the dosage
      of contrast and radiation and increase safety in the performance of procedural
      steps.

PMID- 29588709
TI  - Interventional Therapies for Resistant Hypertension: A Brief Update.
AB  - Resistant hypertension remains a clinical challenge with few management options
      beyond maximisation of medications. Catheter- based renal artery denervation
      (RDN) was proposed in 2009 as a possible therapy for resistant hypertension and
      early feasibility trials caused excitement among cardiologists and
      antihypertensive specialists, showing remarkable and sustained blood pressure
      reductions. In 2014, enthusiasm for RDN dampened following the SYMPLICITY 3 trial
      results, which showed no statistically significant difference in blood pressure
      between the intervention and control arms. However, hope remains for the improved
      management of resistant hypertension; procedural understanding, technological
      advancements and alternative targets - such as baroreceptor activation therapy
      and arteriovenous shunts - may aid the identification of those patients for whom
      specific interventional therapies will be effective.

PMID- 29588710
TI  - Simulator Training in Interventional Cardiology.
AB  - Simulator training in interventional cardiology is becoming a central part of
      early career acquisition of technical and non-technical skills. Its use is now
      mandated by national training organisations. Haptic simulators, part-task
      trainers, immersive environments and simulated patients can provide benchmarked,
      reproducible and safe opportunities for trainees to develop without exposing
      patients to the learning curve. However, whilst enthusiasm persists and trainee
      centred evidence has been encouraging, simulation does not yet have a clear link
      to improved clinical outcomes. In this article we describe the range of
      simulation options, review the evidence for their efficacy in training and
      discuss the delivery of training in technical skills as well as human factor
      training and crisis resource management. We also review the future direction and
      barriers to the progression of simulation training.

PMID- 29588711
TI  - Foreword.

PMID- 29588712
TI  - Transradial Approach in Primary Percutaneous Coronary Intervention: Lessons from
      a High-volume Centre.
AB  - The transradial approach (TRA) is the recommended technique for percutaneous
      coronary intervention (PCI) in acute coronary syndrome, according to the European
      Society of Cardiology guidelines. There is a large body of evidence showing
      reduction in bleeding and mortality when the TRA is used. The TRA is also more
      convenient for patients, by allowing early mobilisation. Finally, by facilitating
      patient turnover and fast (re)transfer after the procedure, the TRA enables
      operators to meet the current recommendations of early invasive therapy in both
      ST and non-ST-elevation myocardial infarction. On the other hand, the TRA is
      technically more challenging than the transfemoral approach (TFA) and requires
      longer learning curve, which hinders its uptake by low-volume operators/centres.
      Nevertheless, in the hands of experienced high-volume operators, such as at Onze
      Lieve Vrouwe Gasthuis (OLVG) Amsterdam, the TRA achieves comparable procedural
      outcomes and favourable clinical results compared with the TFA, as it is in cases
      of primary PCI.

PMID- 29588713
TI  - Expert Opinion Percutaneous Coronary Intervention in Older People: Does Age Make
      a Difference?
AB  - As many people are living longer, much older patients are now commonly being seen
      in clinical practice. The management of coronary disease in this group presents
      formidable challenges. We review the epidemiology of coronary disease in this
      population and report on the burden of comorbidity, influence of frailty,
      problems with polypharmacy, interactions and compliance for the older patient. We
      discuss the management of stable and acute coronary syndromes, the specific
      anatomical challenges of the older coronary artery, the outcomes of the limited
      number of trials involving older patients, and review the guidelines available.

PMID- 29588714
TI  - Preventing Contrast-induced Renal Failure: A Guide.
AB  - Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid
      deterioration of renal function within a few days of parenteral administration of
      contrast media (CM) in the absence of alternative causes. CI-AKI is the most
      common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 %
      in patients undergoing percutaneous coronary intervention. Although usually self
      resolving, in patients with pre-existing chronic kidney disease (CKD) or
      concomitant risk factors for renal damage, CI-AKI is associated with increased
      short-and long-term morbidity and mortality. Therefore, risk stratification based
      on clinical and peri-procedural characteristics is crucial in selecting patients
      at risk of CI-AKI who would benefit the most from implementation of preventive
      measures.

PMID- 29588715
TI  - Fractional Flow Reserve Measurement by Computed Tomography: An Alternative to the
      Stress Test.
AB  - Recent advances in computed tomographic technology have contributed towards
      improving coronary computed tomography angiography (CCTA) in determining the
      severity of coronary artery disease anatomically. Although the viability of CCTA
      has most often been confined to anatomical assessment, recent development has
      enabled evaluation of the haemodynamic significance of coronary artery disease.
      In light of this, CCTA-derived fractional flow reserve (FFRCT), a novel imaging
      modality, now permits the physiological assessment of coronary artery disease. To
      date, several studies have documented the diagnostic performance of FFRCT, and
      more trials are being performed that will further substantiate this technique.
      The present paper provides an overview and discussion of the available evidence
      for FFRCT in the clinical setting as well as potential future directions of
      FFRCT.

PMID- 29588716
TI  - Drug-coated Balloon-only Angioplasty for Native Coronary Disease Instead of
      Stents.
AB  - Coronary angioplasty has vastly improved both in technique and devices since the
      first angioplasty in 1977. Currently, stent implantation is used almost
      ubiquitously, despite being developed originally to treat vessel threatening
      dissections. Newer concepts including absorbable polymers or fully bioabsorbable
      scaffolds are constantly being developed. However, we find the concept of no
      permanent implant whilst still delivering a chemotherapeutic drug to reduce
      restenosis very attractive given the long term implications of a metallic stent,
      which include restenosis, late thrombosis and neo-atheroma formation. The use of
      a drug-coated balloon-only approach to de novo angioplasty will avoid the late
      thrombotic problems whilst also reducing early restenosis, simplifying the
      procedure and reducing the dual antiplatelet duration to 1 month. We review the
      current literature and highlight our practice with regard to use of drug-coated
      balloons in treatment of de novo coronary artery disease.

PMID- 29588717
TI  - The FAME Trials: Impact on Clinical Decision Making.
AB  - Careful and stepwise evaluation of the fractional flow reserve (FFR) index has
      been performed over the years, culminating in the landmark Fractional Flow
      Reserve Versus Angiography for Multivessel Evaluation (FAME) and Fractional Flow
      Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment
      Versus Optimal Medical Treatment Alone in Patients with Stable Coronary Artery
      Disease (FAME II) trials. Findings from these studies demonstrated unequivocally
      the overall inadequacy of angiography versus FFR to correctly assess stenosis
      severity. Thus, proof of concept and clinical applicability was established
      beyond debate and will be discussed here.

PMID- 29588718
TI  - Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable
      Atherosclerotic Plaque.
AB  - The identification of vulnerable atherosclerotic plaques in the coronary arteries
      is emerging as an important tool for guiding atherosclerosis diagnosis and
      interventions. Assessment of plaque vulnerability requires knowledge of both the
      structure and composition of the plaque. Intravascular photoacoustic (IVPA)
      imaging is able to show the morphology and composition of atherosclerotic plaque.
      With imminent improvements in IVPA imaging, it is becoming possible to assess
      human coronary artery disease in vivo. Although some challenges remain, IVPA
      imaging is on its way to being a powerful tool for visualising coronary
      atherosclerotic features that have been specifically associated with plaque
      vulnerability and clinical syndromes, and thus such imaging might become valuable
      for clinical risk assessment in the catheterisation laboratory.

PMID- 29588719
TI  - The Need For Dedicated Bifurcation Stents: A Critical Analysis.
AB  - There is growing evidence that optimally performed two-stent techniques may
      provide similar or better results compared with the simple techniques for
      bifurcation lesions, with an observed trend towards improvements in clinical
      and/or angiographic outcomes with a two-stent strategy. Yet, provisional stenting
      remains the treatment of choice. Here, the author discusses the evidence - and
      controversies - concerning when and how to use complex techniques.

PMID- 29588720
TI  - Non-coronary Interventions: An Introduction to Peripheral Arterial Interventions.
AB  - With an ageing population, the burden of peripheral artery diseases (PADs) is
      increasing. The treatment of these diseases has largely been performed by
      interventional radiologists, vascular surgeons and interventional cardiologists.
      Due to the strong relationship between PAD and overall cardiovascular morbidity
      and mortality, cardiologists need to play a greater role in the management of
      PAD. The physician who cares for the patient with peripheral vascular disease
      should have a broad understanding of atherosclerotic disease involving all
      vascular beds. Endovascular interventions play a major role in relieving symptoms
      and reducing morbidity related to PAD, but long-term optimal medical treatment is
      an essential determinant of prognosis. This paper reviews current
      endovascular/percutaneous interventions for PAD.

PMID- 29588722
TI  - Foreword.

PMID- 29588721
TI  - The Changing Paradigm in the Treatment of Structural Heart Disease and the Need
      for the Interventional Imaging Specialist.
AB  - Percutaneous interventions in structural heart diseases are emerging rapidly. The
      variety of novel percutaneous treatment approaches and the increasing complexity
      of interventional procedures are associated with new challenges and demands on
      the imaging specialist. Standard catheterisation laboratory imaging modalities
      such as fluoroscopy and contrast ventriculography provide inadequate
      visualisation of the soft tissue or three-dimensional delineation of the heart.
      Consequently, additional advanced imaging technology is needed to diagnose and
      precisely identify structural heart diseases, to properly select patients for
      specific interventions and to support fluoroscopy in guiding procedures. As
      imaging expertise constitutes a key factor in the decision-making process and in
      the management of patients with structural heart disease, the sub-speciality of
      interventional imaging will likely develop out of an increased need for high
      quality imaging.

PMID- 29588723
TI  - Use of Intravascular Ultrasound Imaging in Percutaneous Coronary Intervention to
      Treat Left Main Coronary Artery Disease.
AB  - Due to its potential prognostic implications and technical complexity,
      revascularisation of left main coronary artery (LMCA) disease requires careful
      consideration. Since publication of the results of the SYNTAX study, and more
      recently the EXCEL and NOBLE trials, there has been particular interest in
      percutaneous revascularisation of the LMCA. It is becoming clear that
      percutaneous revascularisation of LMCA disease requires appropriate lesion
      preparation and carefully optimised stenting in order to offer patients a
      treatment option as effective as coronary artery bypass grafting. For this reason
      intravascular imaging, and especially intravascular ultrasound, is becoming a key
      procedural step in LMCA percutaneous coronary intervention. In the current review
      paper we analyse the role of intravascular imaging with intravascular ultrasound
      in LMCA percutaneous coronary intervention, focusing on the main applications in
      this context from lesion assessment to stent sizing and optimisation.

PMID- 29588724
TI  - PCI in Patients with Diabetes: Role of the Cre8 Drug-eluting Stent.
AB  - Patients with diabetes have poor outcomes compared to the general patient
      population when undergoing percutaneous coronary intervention. The Cre8TM
      (Alvimedica) drug-eluting stent (DES) has unique features that may improve
      clinical outcomes in patients with diabetes. These include abluminal reservoir
      technology, a proprietary polymer-free drug-release system consisting of
      reservoirs on the stent's outer surface that control and direct drug release
      exclusively towards the vessel wall, and the AmphilimusTM formulation, which
      enables enhanced drug tissue permeation, utilising fatty acid transport pathways.
      This is particularly advantageous in diabetic patients, since increased uptake of
      fatty acid occurs in diabetic cells. Furthermore, mTOR inhibitors (-limus drugs),
      which are utilised in DESs, are relatively ineffective in diabetic cells.
      Clinical efficacy and safety of the Cre8TM in patients with diabetes has been
      demonstrated in a number of clinical trials and real-world studies, and further
      studies are on-going.

PMID- 29588725
TI  - Expert Opinion: Transradial Coronary Artery Procedures: Tips for Success.
AB  - Historically, the majority of coronary procedures have been performed via the
      femoral artery. However, since the inception of the transradial approach, a
      number of studies have confirmed that this technique is associated with a
      significant reduction in vascular complications, equivalent procedure times and
      radiation exposure to femoral procedures, the ability to perform complex coronary
      interventions, early ambulation and patient preference. Over the last decade,
      this has led to an exponential rise in the use of the transradial access site,
      with several potential technical challenges becoming increasingly recognised.
      However, with greater experience and technological advancement these potential
      obstacles may be overcome. The following review highlights the potential
      challenges and suggests several tips to assist transradial operators with
      recognising and overcoming these challenges.

PMID- 29588726
TI  - Managing Stroke During Transcatheter Aortic Valve Replacement.
AB  - Transcatheter aortic valve replacement (TAVR) has become the default treatment
      option for high-risk patients with aortic stenosis and an alternative to surgical
      aortic valve replacement in intermediate-risk patients. There are, however,
      concerns regarding strokes during TAVR. Reported stroke rates vary strongly
      depending on the type of study, stroke definition, cohort and study period.
      Furthermore, stroke after TAVR occurs in three distinct phases: 1) early high
      risk, directly procedure related; 2) elevated risk interval between day 2 and day
      30; 3) late hazard interval. Each of these phases is caused by the different
      aetiologies of stroke. This review summarises the different aetiologies and
      potential strategies for managing stroke during TAVR.

PMID- 29588727
TI  - Use of Embolic Protection Devices in Peripheral Interventions.
AB  - The use of embolic protection devices (EPDs) when treating coronary saphenous
      vein bypass grafts, performing carotid arterial stenting and treating acute
      coronary syndromes is well accepted. We will review currently available devices
      and approaches to reduce distal embolisation, first discussing their uses in
      carotid interventions and then in vertebral and peripheral vascular
      interventions.

PMID- 29588728
TI  - Need for Embolic Protection During Transcatheter Aortic Valve Implantation: An
      Interventionalist's Perspective on Histopathology Findings.
AB  - Transcatheter aortic valve implantation (TAVI) is a less invasive aortic valve
      replacement technique and is indicated for patients with symptomatic severe
      aortic stenosis and a high operative risk. Cerebral embolisation seems inherent
      to TAVI, as illustrated by the consistent appearance of new brain lesions on post
      procedural MRI studies. Embolic protection devices may capture or deflect
      embolised material en route to the brain and thus reduce TAVI-related brain
      injury. Histopathology studies of captured debris revealed a diverse aetiology
      including recent or organised thrombotic material, tissue originating from the
      aortic valve, atherosclerotic plaques or myocardium and foreign body components.
      In this overview we provide a perspective on current evidence and implications
      for embolic protection devices in the dynamic TAVI field.

PMID- 29588729
TI  - Optimising the Haemodynamics of Aortic Valve-in-valve Procedures.
AB  - Bioprosthetic surgical valves are increasingly implanted during cardiac surgery,
      instead of mechanical valves. These tissue valves are associated with limited
      durability and as a result transcatheter valve-in-valve procedures are performed
      to treat failed bioprostheses. A relatively common adverse event of aortic valve
      in-valve procedures is residual stenosis. Larger surgical valve size, supra
      annular transcatheter heart valve type, as well as higher transcatheter heart
      valve implantation depth, have all been shown to reduce the incidence of elevated
      post-procedural gradients. With greater understanding of technical considerations
      and surgical planning, valve-in-valve procedures could be more effective and
      eventually may become the standard of care for our increasingly ageing and
      comorbid population with failed surgical bioprostheses.

PMID- 29588730
TI  - A Glimpse into the Future: In 2020, Which Patients will Undergo TAVI or SAVR?
AB  - Transcatheter aortic valve implantation (TAVI) has evolved into a safe and
      effective procedure to treat symptomatic patients with severe aortic stenosis
      (AS), with predictable and reproducible results. Rates of important complications
      such as vascular complications, strokes and paravalvular leaks are lower than
      ever, because of improved patient selection, systematic use of multidector
      computer tomography, increasing operator experience and device iteration.
      Accumulating data suggest that transfemoral TAVI with newer generation
      transcatheter heart valves and delivery systems is superior to conventional
      surgical aortic valve replacement among intermediate- and high-risk patients with
      severe symptomatic AS with regard to all-cause mortality and stroke. One can
      anticipate that by 2020, the majority of patients with severe symptomatic AS will
      undergo TAVI as first line therapy, regardless of surgical risk.

PMID- 29588731
TI  - Management of Tricuspid Regurgitation: The Role of Transcatheter Therapies.
AB  - Surgical treatment is the gold standard treatment of functional tricuspid
      regurgitation (FTR) but this carries high risks of morbidity and mortality.
      Percutaneous procedures are an attractive alternative to surgery for selected
      patients deemed to be high-risk surgical candidates. A number of tricuspid
      transcatheter devices have been developed to treat FTR, but at present, evidence
      of their efficacy and safety is scarce. Preliminary data have shown promising
      results, but ongoing and future studies will provide a clearer picture of the
      benefits of these new techniques.

PMID- 29588732
TI  - Aortic Dissection: Novel Surgical Hybrid Procedures.
AB  - The management of patients with aortic dissection is challenging and its
      treatment is an area of development and innovation. Conventional surgical
      techniques are associated with significant risks in terms of mortality and
      morbidity in such high-risk patients. As a result of cumulative advances in
      technology, classical surgical techniques have been improved and enhanced by the
      newer endovascular approaches, leading to novel surgical hybrid procedures.
      Impressive early results have been seen with frozen elephant techniques,
      revascularisation of the supra-aortic branches and branched/fenestrated thoracic
      endovascular aortic repair-alone procedures. This review describes the techniques
      involved in the latest hybrid procedures for aortic dissection and their
      outcomes.

PMID- 29588733
TI  - Foreword.

PMID- 29588734
TI  - Expert Opinion: Optimising Stent Deployment in Contemporary Practice: The Role of
      Intracoronary Imaging and Non-compliant Balloons.
AB  - Final stent dimensions remain an important predictor of restenosis, target vessel
      revascularisation (TVR) and subacute stent thrombosis (ST), even in the drug
      eluting stent (DES) era. Stent balloons are usually semi-compliant and thus even
      high-pressure inflation may not achieve uniform or optimal stent expansion. Post
      dilatation with non-compliant (NC) balloons after stent deployment has been shown
      to enhance stent expansion and could reduce TVR and ST. Based on supporting
      evidence and in the absence of large prospective randomised outcome-based trials,
      post-dilatation with an NC balloon to achieve optimal stent expansion and maximal
      luminal area is a logical technical recommendation, particularly in complex
      lesion subsets.

PMID- 29588735
TI  - Current State of the Art in Approaches to Saphenous Vein Graft Interventions.
AB  - Saphenous vein grafts (SVGs), used during coronary artery bypass graft surgery
      for severe coronary artery disease, are prone to degeneration and occlusion,
      leading to poor long-term patency compared with arterial grafts. Interventions
      used to treat SVG disease are susceptible to high rates of periprocedural MI and
      no-reflow. To minimise complications seen with these interventions, proper
      stents, embolic protection devices (EPDs) and pharmacological selection are
      crucial. Regarding stent selection, evidence has demonstrated superiority of drug
      eluting stents over bare-metal stents in SVG intervention. The ACCF/AHA/SCA
      American College of Cardiology/American Heart Association Task Force on Clinical
      Practice Guidelines and the Society for Cardiovascular Angiography and
      Interventions guidelines recommend the use of EPDs during SVG intervention to
      decrease the risk of periprocedural MI, distal embolisation and no-reflow. The
      optimal pharmacological treatment for slow or no-reflow remains unclear, but
      various vasodilators show promise.

PMID- 29588736
TI  - Unprotected Left Main Coronary Artery Disease: Management in the Post NOBLE and
      EXCEL Era.
AB  - The optimal management of unprotected left main coronary artery (ULMCA) disease
      is currently a debated topic. Percutaneous coronary intervention (PCI) has seen
      an increased adoption for the management of ULMCA disease after numerous small
      scale randomised trials and cohort studies showed equipoise with coronary artery
      bypass grafting (CABG) for low complexity lesions. The recently published NOBLE
      and EXCEL trials are two of the largest international randomised clinical trials
      comparing PCI and CABG in patients with ULMCA disease. In lieu of all the
      available evidence, PCI appears to be equivalent to CABG in regard to mortality
      in patients with ULMCA disease. In non-diabetic patients with low complexity
      coronary disease (SYNTAX score <=32), PCI appears to be a reasonable alternative
      to CABG, especially for ostial and midshaft left main coronary lesions. CABG is
      preferable in the presence of diabetes, multivessel coronary disease in addition
      to ULMCA or complex coronary lesions (SYNTAX score >33) including distal left
      main lesions.

PMID- 29588737
TI  - Performing and Interpreting Fractional Flow Reserve Measurements in Clinical
      Practice: An Expert Consensus Document.
AB  - Fractional flow reserve (FFR) measurements can determine the haemodynamic
      relevance of coronary artery stenoses. Current guidelines recommend their use in
      lesions in the absence of non-invasive proof of ischaemia. The prognostic impact
      of FFR has been evaluated in randomised trials, and it has been shown that
      revascularisation can be safely deferred if FFR is >0.80, while revascularisation
      of stenoses with FFR values <=0.80 results in significantly lower event rates
      compared to medical treatment. Left main stenoses, aorto-ostial lesions, as well
      as patients with left ventricular hypertrophy and severely-impaired ejection
      fraction, have been excluded from large, randomised trials. While FFR
      measurements are relatively straightforward to perform, uncertainty about
      procedural logistics, as well as data acquisition and interpretation in specific
      situations, could explain why they are not widely used in clinical practice. We
      summarise the clinical data in support of FFR measurements, and provide
      recommendations for performing and interpreting the procedure.

PMID- 29588738
TI  - The Proximal Optimisation Technique for Intervention of Coronary Bifurcations.
AB  - The proximal optimisation technique (POT) has been proposed as a strategy to
      improve the results of stent scaffolding of bifurcation lesions. It is a
      straightforward technique whereby a short, appropriately-sized balloon is
      inflated in the main vessel just proximal to the carina. The technique has
      several advantages: it reduces the risk of side branch compromise related to
      shifting of the carina, it improves stent apposition in the proximal main vessel,
      and it facilitates side branch access after main vessel stent implantation. When
      treating bifurcations, final kissing balloon dilation (KBD) has traditionally
      been used routinely to optimise angiographic results. However, recent clinical
      data have questioned this philosophy and bench models have demonstrated several
      shortcomings of KBD. Instead, the optimal strategy may centre on performing POT,
      followed by side branch dilation, and completed with a final (re)-POT. The
      following review article describes how to perform POT and presents the evidence
      to support its' routine use.

PMID- 29588740
TI  - Expert Opinion Will PARTNER 2 Change My Practice?
AB  - Transcatheter aortic valve implantation (TAVI) has become an established and
      increasingly-used technique to treat patients with severe aortic valve stenosis
      (AS) over the past decade. The clinical outcomes obtained with TAVI have been
      found to be equivalent to surgical aortic valve replacement (SAVR) in patients
      with a high-risk profile. Following the Placement of Aortic Transcatheter Valves
      (PARTNER) 1 trial, which demonstrated the utility of TAVI in inoperable and high
      risk groups, the PARTNER 2 trial was implemented. PARTNER 2 reflects the current
      TAVI practice in Europe, confirms that transfemoral access is related to superior
      outcomes compared to SAVR in a selected population and demonstrates improved
      results with new-generation devices.

PMID- 29588739
TI  - Predilatation Prior to Transcatheter Aortic Valve Implantation: Is it Still a
      Prerequisite?
AB  - Predilatation has been historically considered a mandatory step before
      transcatheter aortic valve implantation (TAVI) since it facilitates valve
      crossing and prosthesis delivery, ensures optimal valve expansion and improves
      hemodynamic stability during valve deployment. However, as a result of procedural
      evolution over time, direct TAVI (without pre-implantation balloon aortic
      valvuloplasty) has emerged as an interesting option to simplify the procedure and
      to avoid potential valvuloplasty-related complications. Several real-world
      retrospective studies and one small randomised study have shown that direct TAVI
      (with both self-expanding and balloon-expandable prostheses) is feasible, safe
      and associated with outcomes similar to standard TAVI with pre-implantation
      balloon aortic valvuloplasty. In the absence of high-quality, robust evidence,
      the current review aims to discuss the advantages and disadvantages of omitting
      predilatation prior to TAVI.

PMID- 29588741
TI  - Safety and Efficacy of Protected Cardiac Intervention: Clinical Evidence for
      Sentinel Cerebral Embolic Protection.
AB  - Stroke is a well-documented potential risk of structural cardiac interventions.
      As a result of the far-reaching burden of stroke on patients, caregivers and the
      healthcare system, new medical interventions and therapies are being developed to
      help mitigate this risk. One such intervention is the recently FDA-cleared
      SentinelTM Cerebral Protection System (Sentinel; Claret Medical, Santa Rosa, CA,
      USA) designed to capture and remove debris dislodged during transcatheter aortic
      valve replacement procedures. In the SENTINEL IDE Study, and in a more recent all
      comers trial, Sentinel significantly reduced periprocedural strokes by 63 and 70
      % respectively. In this paper, we review the growing body of evidence supporting
      the use of Sentinel in transcatheter aortic valve replacement and other
      endovascular procedures.

PMID- 29588742
TI  - Expert Opinion: Guidelines for the Management of Patients with Aortic Stenosis
      Undergoing Non-cardiac Surgery: Out of Date and Overly Prescriptive.
AB  - Patients with severe aortic stenosis who require non-cardiac surgery present a
      difficult clinical problem. The most recent clinical practice guidelines from the
      American College of Cardiology/American Heart Association and the European
      Society of Cardiology for the perioperative cardiovascular assessment and
      management of patients undergoing noncardiac surgery were both published in 2014.
      These guidelines are reviewed in the light of recently published randomised
      controlled trial data regarding the efficacy of transcatheter aortic valve
      implantation to treat aortic stenosis.

PMID- 29588743
TI  - Foreword.

PMID- 29588745
TI  - Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention for
      Unprotected Left Main Disease - A Review.
AB  - There have been over a dozen studies in the drug-eluting stent era comparing the
      effectiveness of percutaneous coronary intervention (PCI) and coronary artery
      bypass graft (CABG) surgery for the treatment of unprotected left main disease.
      These studies have been both randomised and observational in nature. While both
      methodologies provide important insights, careful consideration of their
      respective strengths and limitations is imperative in generalising their
      findings.

PMID- 29588744
TI  - Acute Coronary Syndrome in Pre- and Post-partum Women - A Review.
AB  - Acute coronary syndrome (ACS) during pregnancy and the post-partum period are
      weighed by a high mortality rate for the mother and foetus. They should be
      considered as multifactorial diseases with a special role for sexual hormones. In
      this setting, ACS is mostly related to an early atherosclerotic disease, even if
      other conditions are responsible. Indeed, an important part is due to spontaneous
      coronary artery dissection, more common during delivery and the post-partum
      period. In the remaining situation, an isolated intracoronary thrombus or a
      normal angiographic pattern can be found at angiography. Pathophysiology is still
      uncertain with different hypothetical mechanisms. Prompt diagnosis of ACS and
      aetiology are essential for an optimal therapeutic strategy. Difficulties in
      treatment management is a matter for debate, especially in pre-partum women. In
      the last two decades improvements of diagnostic tools, coronary angiography and
      subsequent percutaneous treatment have changed the natural history of this rare
      condition.

PMID- 29588746
TI  - Dedicated Bifurcation Drug-eluting Stent BiOSS(r) - A Novel Device for Coronary
      Bifurcation Treatment.
AB  - The Bifurcation Optimisation Stent System (BiOSS(r)) (Balton(r), Poland) is a
      coronary, dedicated bifurcation, balloon-expandable stent made of 316 litre
      stainless steel tube with strut thickness of 120 micrometre (um). It is covered
      with a mixture of a biodegradable polymer and an antiproliferative substance -
      paclitaxel (BiOSS Expert version) or sirolimus (BiOSS Lim version). The stent
      consists of two parts (the proximal with a larger diameter in relation to the
      distal one) connected with two connection struts (average 1.2 mm in length) at
      the step-up middle zone. The stent is crimped on a bottle-shaped semi-complaint
      balloon (Bottle(r), Balton, Poland). Our intravascular ultrasound (IVUS) study
      revealed that the construction of the BiOSS stent assures an easy access to the
      side branch and is comparable to the classic stent lumen enlargement with less
      injury to the area adjacent to the most sensitive part of the bifurcation. A
      total number of 65 lesions in 63 consecutive patients were enrolled in the First
      In-Man (FIM) registry for BiOSS Expert, where we achieved a 100 % device success
      rate. The long-term clinical results were satisfactory and closely related to the
      high-risk profile of the treated population. Our data demonstrated that simple
      and fast bifurcation treatment with a single dedicated bifurcation paclitaxel
      eluting stent (BiOSS Expert) is feasible and highly successful. Based on the data
      collected in animal experiments and preliminary data in humans with BiOSS Lim,
      releasing sirolimus from the surface of the biodegradable coating, one may
      presume that this version will provide even better clinical results compared with
      the paclitaxel one.

PMID- 29588748
TI  - Understanding and Minimising Occupational Radiation in the Catheterisation
      Laboratory with PISAX and the ACIST CVi(r) Contrast Delivery System.
AB  - This paper provides an overview of radiation exposure and its associated risks in
      the cardiac catheterisation laboratory (cath lab), as well as strategies to
      minimise radiation exposure for operators, cath lab staff and patients. The
      benefits of using a mobile 2 mm lead equivalent radiation shield (PISAX) and
      adoption of an automated contrast injection system (the ACIST CVi(r) Contrast
      Delivery System) are discussed, and the potential advantages of their combination
      are reviewed.

PMID- 29588747
TI  - Invasive Imaging of Bioresorbable Coronary Scaffolds - A Review.
AB  - Various fully bioresorbable stents (BRS) have been recently developed, allowing
      for temporary scaffolding of the vessel wall. The potentially unique advantage of
      BRS to temporary scaffold the vessel could reduce the risk of adverse clinical
      outcomes caused by acute vessel geometry changes, late malapposition, jailed side
      branches or inflexibility of permanent stents. The design of BRS is, however, not
      similar for all stents, resulting in differences in degradation and behaviour. To
      assess the performance of BRS, the effect of degradation and behaviour on the
      vessel wall should be accurately evaluated. Intracoronary imaging techniques such
      as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near
      infrared spectroscopy (NIRS) allow for detailed longitudinal evaluation of the
      stent and the vessel wall and might therefore aid in improving design and
      behaviour of BRS.

PMID- 29588749
TI  - Coronary Chronic Total Occlusion Recanalisation - Current Techniques and
      Approaches.
AB  - Coronary chronic total occlusions (CTOs) are among the most challenging coronary
      artery lesions to treat percutaneously. In the last decade, great strides have
      been made to develop techniques to improve success rates. While success rates
      among high-volume operators are >90 %, non-CTO operators still continue to
      struggle with this lesion subset. Thus, efforts have been made to develop
      algorithms to help operators achieve successful recanalisation consistently and
      improve patient outcomes. The North American Total Occlusion (NATO) algorithm
      emphasises dual coronary injection using two guide catheters, which allows for
      switching from an antegrade to retrograde approach or vice versa should the
      initial strategy fail - the so-called 'hybrid' approach. Special attention is
      paid to four angiographic characteristics: 1) location of the proximal cap, 2)
      lesion length, 3) presence and suitability of collateral vessels for retrograde
      crossing and 4) location and quality of target vessel distal cap. The ultimate
      goal of this algorithm is to provide a strategy to achieve successful CTO
      revascularisation while using the least amount of fluoroscopy, contrast and
      equipment possible.

PMID- 29588750
TI  - Double Chronic Total Occlusion Recanalisation with Antegrade and Retrograde
      Techniques and the Use of a Novel Drug-eluting Stent with Biodegradable Polymer.
AB  - Percutaneous recanalisation of coronary chronic total occlusions (CTOs) has
      proved an efficient and safe treatment option with steadily ascending success
      rates, especially since the advent and constant refinement of the retrograde
      approach. Uptake remains low, even though experienced operators have in the last
      five years reached an unprecedented maturity level, producing success rates in
      the range of 90 %, clearly comparable to non-occlusive coronary artery disease
      treatment. Antegrade and retrograde techniques are currently considered
      complementary components of a CTO procedure, rather than discrete treatment
      strategies. We report on the case of a successful CTO recanalisation procedure on
      a young patient with two chronically occluded coronary arteries and a large
      ischaemic burden. Both CTOs were addressed in the same session employing a range
      of dedicated CTO recanalisation techniques, without compromising on safety issues
      related to contrast dye consumption and radiation exposure. A novel drug-eluting
      stent (DES) with biodegradable polymer was used to treat the lesions.

PMID- 29588751
TI  - Carotid Artery Stenting - Strategies to Improve Procedural Performance and Reduce
      the Learning Curve.
AB  - Carotid artery stenting (CAS) remains an appealing intervention to reduce the
      stroke risk because of its minimal invasive nature. Nevertheless, landmark
      randomised controlled trials have not been able to resolve the controversies
      surrounding this complex procedure as the peri-operative stroke risk in a non
      selected patient population still seems to be higher after CAS in comparison to
      carotid endarterectomy. What is more, these trials have highlighted that patient
      outcome after CAS is influenced by patient- and operator-dependant factors. The
      CAS procedure exhibits a definitive learning curve resulting in higher
      complication rates if the procedure is performed by inexperienced
      interventionists or in low-volume centres. This article will outline strategies
      to improve the performance of physicians carrying out the CAS procedure by means
      of proficiency-based training, credentialing, virtual reality rehearsal and
      optimal patient selection.

PMID- 29588752
TI  - Endovascular Abdominal Aortic Aneurysm Repair - Patient Selection and Long-term
      Outcome Expectations - Current Challenges in 2013.
AB  - Endografts for repair of abdominal aortic aneurysm were first reported in the
      late 1980s and commercially available grafts were developed rapidly during the
      1990s. This prompted a head-to-head comparison of the new, less invasive,
      endovascular technology with the existing gold standard of open repair. The first
      and largest randomised trial of open versus endovascular repair for large
      aneurysms started in the UK in 1999. Other trials comparing open and endovascular
      repair followed in the Netherlands, France and the US. Only the UK trial has
      reported long-term follow-up to 10 years. This has shown no statistically
      significant difference in long-term survival after open or endovascular repair.
      Aneurysm-related mortality curves converged at six years, which is described as
      endovascular aortic repair (EVAR) 'catch up' on open repair. It appears that this
      convergence is probably largely attributable to secondary sac rupture after
      endovascular repair, which is fatal in about two-thirds of cases. At this point,
      we have reached a crossroads and only longer-term follow-up data can provide the
      vital answer to the outcome of endovascular repair in the long run. This article
      gives a brief overview of the development and the current evidence of
      endovascular aortic repair and discusses the most important factors that are
      leading the way to the future of this technology.

PMID- 29588753
TI  - Foreword.

PMID- 29588754
TI  - Evidence-based Management of Cardiogenic Shock After Acute Myocardial Infarction.
AB  - Guidelines for evidence-based management of patients with cardiogenic shock after
      acute myocardial infarction focuses on early revascularisation of the occluded
      coronary artery as well as on support of cardiac failure and improvement of
      impaired organ perfusion. Also of great importance is effective treatment of
      shock complications, especially acute respiratory failure and other forms of
      multiple organ dysfunction syndrome (MODS). Cardiovascular therapy has to be
      accompanied by best general intensive care of these critically ill patients with
      high mortality. Most lives can be saved by early revascularisation, and this
      class I recommendation has a high level of evidence. So far, most of the other
      guideline recommendations are of low evidence level, in most cases based on
      expert opinions. Recently, the Intra-aortic Balloon Pump in Cardiogenic Shock II
      (IABP SHOCK II) trial with 600 patients has shown that adjunctive IABP therapy -
      for long a class I recommendation - does not reduce 30-day and six-month
      motality.

PMID- 29588755
TI  - The Role of the Transradial Approach for Complex Coronary Interventions in
      Patients with Acute Coronary Syndrome.
AB  - Despite advances in antithrombotic and antiplatelet therapy, bleeding
      complications remain an important cause of morbidity and mortality in patients
      with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention
      (PCI). A significant proportion of such bleedings are related to the access site,
      and adoption of transradial access (TRA) may reduce these complications. In
      patients with ST-segment elevation myocardial infarction (STEMI), TRA reduced
      cardiac mortality in comparison with the femoral approach (TFA). High-risk
      patients such as women, obese patients and elderly subjects who are at increased
      risk for vascular complications and bleeding, might particularly benefit from the
      TRA. However, specific radial expertise providing procedural time and a success
      rate comparable to those with the TFA are strongly recommended before using this
      technique in the emergency setting.

PMID- 29588756
TI  - The Role of Bioresorbable Scaffolds in Meeting the Challenges of Bifurcations.
AB  - Side branches are frequently related to periprocedural complications. Considering
      any side branches >1 millimetres (mm), side branch occlusion or reduced flow may
      occur in approximately 10 % of interventional procedures. First data indicate
      that bioresorbable vascular scaffolds (BVS) behave similar compared with modern
      drug-eluting stents (DES) with regard to compromising or occluding sizeable side
      branches. Although technically more demanding compared with modern DES, it
      appears to be feasible to dilate side branches after crossing BVS cells.
      Preliminary data suggest at least balloon diameters up to 2.5 mm can be used, but
      safety remains unclear. Instead of kissing balloon dilatation, rather sequential
      balloon dilatation should be employed. Anecdotic evidence suggests BVS can be
      used even in relatively complex coronary anatomy, e.g. bifurcations distal to
      chronic total occlusion. Certainly more data are needed. As of today, BVS offer
      promise not only for the treatment of simple coronary lesions but also
      bifurcations. Given successful side branch protection, they might allow for
      restoring the native coronary anatomy in the sense of restitutio ad integrum.

PMID- 29588757
TI  - How to Select the Most Appropriate Patient and Lesion to be Treated with a
      Coronary Bioresorbable Vascular Scaffold.
AB  - Bioresorbable vascular scaffolds (BVS) are an exciting novel treatment for
      coronary artery disease (CAD) as their eventual resorption renders the artery
      free from a permanent metallic cage. Clinical trials regarding these novel
      devices have demonstrated promising results, although their use in this context
      has largely been restricted to simple lesions. More recently, BVS use has
      expanded to patients with more complex lesions including those with long diffuse
      disease, and results from several registries are awaited with regard to their
      efficacy in 'real-world' patients. Although any patient who requires percutaneous
      treatment for CAD could benefit from BVS implantation, there are certain cohorts
      of patients and lesions in whom BVS could be of particular benefit. In this
      review, we attempt to identify which patient and lesion cohort is most suitable
      for treatment with these novel devices.

PMID- 29588758
TI  - Personal Experience with Bioresorbable Scaffolds in Bifurcations.
AB  - Bioresorbable scaffolds represent a promising new technology in the field of
      percutaneous coronary interventions. The concept of the eventual resorption of
      the scaffold pertains to multiple theoretical advantages that may hold true
      particularly in bifurcation lesions - no permanent caging of the coronary artery,
      avoidance of acquired device malapposition and delayed hypersensitivity
      reactions, no permanent metallic stent protrusion in the main branch, etc. The
      worldwide experience with the use of bioresorbable scaffolds is limited. In our
      experience of selected bifurcation lesions, a provisional approach using one
      scaffold has excellent results. Two-scaffold techniques appeared feasible. Our
      data support the exploration of the use of bioresorbable scaffolds in more
      challenging coronary substrates like bifurcations. Prospective registries and
      ideally randomised trials should assess whether the theoretical benefits of
      bioresorbable vascular scaffolds (BVS) in bifurcation lesions can produce
      sustainable good clinical outcomes.

PMID- 29588759
TI  - Technical Aspects of Provisional Stenting in Percutaneous Treatment of Complex
      Bifurcation Lesions.
AB  - Drug-eluting stent (DES) implantation using the 'provisional' approach is the
      gold standard for percutaneous treatment of patients with unselected bifurcated
      lesions. Nevertheless, many operators still consider the provisional approach
      unsuitable for coronary patients with complex bifurcation anatomies. Yet, the
      provisional approach may be so differently carried out that its procedural
      outcome is often unpredictable. Some technical refinements may help to anticipate
      or manage procedural difficulties, which may occur during the management of
      complex patients. We sought to overview the issues related with DES selection as
      well as some technical points, which may increase the effectiveness of
      provisional stenting. In particular, the DES characteristics influencing
      bifurcation interventions and the technical refinements, which may be considered
      during a provisional stenting procedure are discussed. Indeed, main vessel stent
      sizing, proximal optimisation, side branch protection modality, side branch
      rewiring, kissing balloon and side branch rescue techniques are all pivotal to
      increase the safety and efficacy of the provisional strategy especially in the
      setting of complex anatomies and patients.

PMID- 29588761
TI  - Challenges in Complicated Coronary Chronic Total Occlusion Recanalisation.
AB  - Percutaneous coronary intervention for chronic total occlusions (CTOs) is still
      today a challenge even for experienced operators. In the hands of the most
      experienced the success rate increased from about 60 to 90 % in the past 10
      years; paralleled by a long-term patency with drug-eluting stents exceeding 90 %.
      These results are comparable or even superior to surgical revascularisation.
      Thanks to Japanese and European CTO club online registries and live courses we
      are able to rapidly understand and adopt new strategies, techniques and materials
      to master morphology deemed untreatable 10 years ago. Several of the persistent
      challenges and solutions unique to CTO interventions are discussed.

PMID- 29588760
TI  - Current Concepts in the Clinical Utility of Platelet Reactivity Testing.
AB  - The pharmacodynamic effect of clopidogrel varies among individuals; approximately
      a third will have high on-treatment platelet reactivity (HTPR) to adenosine
      diphosphate and may benefit from more intensive antiplatelet therapy. Platelet
      reactivity testing has an important role in monitoring the therapeutic efficiency
      of clopidogrel and the safety of more potent drugs that confer an increased
      bleeding risk, because it provides a direct measure of the biological effect of
      these drugs. Numerous studies have demonstrated an association between HTPR and
      the risk of cardiac events in acute coronary syndrome (ACS) or after percutaneous
      coronary intervention (PCI). While the prognostic value of platelet reactivity
      testing following PCI has been demonstrated repeatedly in cohort studies and meta
      analyses, randomised controlled studies investigating the clinical utility of the
      technique to guide treatment decisions failed to improve clinical outcomes of
      clopidogrel-treated patients undergoing stent implantation. Available data
      suggest that platelet function monitoring may be carried out in clopidogrel
      treated patients with a higher risk of thrombotic events. These include patient
      risk factors such as body mass index (BMI), type 2 diabetes, and those prior
      unexpected ischemic events such as stent thrombosis, as well as procedural risk
      factors. As we move towards conclusively defining a therapeutic window associated
      with both cardiovascular (upper threshold) and bleeding risk (lower threshold)
      for antiplatelet agents, platelet reactivity testing will become a central tool
      in the practice of personalised strategies.

PMID- 29588762
TI  - The Anatomic-Functional Duality of So-called 'Significant' Atherosclerotic
      Stenosis - Update on Invasive Diagnostic Strategies in Coronaropathy.
AB  - So-called 'significant' atherosclerotic coronary stenosis is defined by a simple
      binary morphological index of tightness - percent diameter stenosis (%DS >50 %).
      Invasive diagnosis of atherosclerotic coronary lesions classically comprises two
      consecutive stages, which can be fairly accurately described as angiographic
      visual perception and functional deduction. This anatomic-functional duality
      should be seen as not so much antithetic as causal and finally quite complex. The
      present update seeks to: define the ambiguous relationship between functional
      impact and morphology in atherosclerotic coronary stenosis; to specify the means
      of invasive diagnosis complementing coronary angiography to compensate the
      anatomic and functional limitations intrinsic to the latter (cross-sectional
      intravascular ultrasound [IVUS] and optical coherence tomography [OCT] imaging
      and fractional flow reserve [FFR] determined by pressure guide); and to bring
      these preliminary considerations to bear on the design of algorithms to guide the
      use of complementary invasive diagnostic exploration and draw up a novel
      diagnostic strategy in interventional cardiology (first-line coronary
      angiography).

PMID- 29588763
TI  - Catheter-based Renal Sympathetic Denervation - Long-term SymplicityTM Renal
      Denervation Clinical Evidence, New Data and Future Perspectives.
AB  - Hypertension is one of the most prevalent chronic diseases worldwide and the
      incidence of resistant hypertension is increasing. Catheter-based renal
      denervation (RDN) offers a new approach to reaching blood pressure goals by
      targeting the renal nerves. The technique has demonstrated significant and
      sustained reductions in blood pressure (BP) in the Symplicity HTN-1 and
      Symplicity HTN-2 clinical trials. The Global SYMPLICITY Registry aims to
      demonstrate safety and effectiveness in a 'real-world' patient population. Real
      world RDN experience has emphasised that patient selection is crucial to
      successful outcomes; a multidisciplinary referral network is recommended to
      increase awareness of the procedure and identify patients who are likely to
      respond best to RDN. Further advances in catheter technology have led to the
      development of the multi-electrode Symplicity SpyralTM multi-electrode catheter;
      preliminary data from the feasibility study using the Symplicity Spyral catheter
      indicate clinical efficacy and procedural safety with reduced procedure times.
      The Symplicity Spyral catheter is not yet commercially available. The indications
      of RDN may also expand beyond resistant hypertension - encouraging data have been
      seen in patients with moderate treatment resistant hypertension. Furthermore, RDN
      may be beneficial in other clinical states characterised by sympathetic nervous
      system overactivation including heart failure and chronic kidney disease.
      Additional data are needed to evaluate the efficacy of RDN in these disease
      states.

PMID- 29588764
TI  - Application in Hypertension of Renal Sympathetic Denervation - A Review.
AB  - Afferent and efferent sympathetic nerves of the kidney located in the adventitia
      of the renal artery are involved in the regulation of blood pressure and play a
      pathophysiological role in the progression and maintenance of hypertension. Renal
      sympathetic denervation is a potent and safe catheter-based therapeutic approach
      for the treatment of patients with resistant hypertension. Clinical trials of
      renal sympathetic denervation have shown significant reduction in blood pressure,
      which was associated with a reduction in local renal norepinephrine spillover as
      well as a reduction of whole body sympathetic activation in resistant
      hypertensive patients.

PMID- 29588766
TI  - Overcoming the Challenges of the Transfemoral Approach in Transcatheter Aortic
      Valve Implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is performed through a retrograde
      transfemoral approach in approximately 80-90 % of cases thanks to the
      improvements in delivery catheter profile, size and steerability compared with
      the first generation devices. The aim of this review article is to describe the
      challenges of transfemoral TAVI and the options to overcome them. The
      difficulties may be related to the access itself or the placement of the valve
      using the transfemoral route. Comprehensive patient screening using multislice
      computed tomography and crossover techniques to prevent bleeding should result in
      low complication rates even for fully percutaneous procedures. Horizontal
      ascending aorta and severely calcified aortic valves remain a challenge for
      retrograde valve crossing, device advancement and accurate positioning during
      deployment. The buddy balloon technique is a simple option in the case of
      difficult aortic valve crossing with a delivery catheter, whereas an antegrade
      approach using the transapical route is a reasonable alternative in such anatomy.

PMID- 29588765
TI  - Concurrent Coronary Artery and Valvular Heart Disease - Hybrid Treatment
      Strategies in 2013.
AB  - Concomitant coronary artery disease (CAD) and valvular heart disease is an
      increasingly common problem in the ageing population. Hybrid procedures combine
      surgical and transcatheter approaches to facilitate minimally invasive surgery or
      to transform a single high-risk open surgery into two less risky procedures. In
      ideal circumstances, this strategy may decrease the surgical risk in elderly,
      high-risk and reoperative surgical candidates, while improving patient comfort,
      convenience and cost-effectiveness. Hybrid procedures can be performed in a
      staged fashion or as a 'one-stop' procedure in a hybrid operating suite.
      Increasing evidence supports the safety and short-term efficacy of hybrid valve
      repair or replacement and coronary revascularisation procedures. Nevertheless,
      important questions remain, including the optimal timing of the individual
      procedures and the optimal antiplatelet therapy after percutaneous coronary
      intervention. With ongoing advances in procedural techniques and anticoagulation
      strategies, as well as the accumulation of long-term outcomes data, hybrid
      approaches to concomitant CAD and valvular heart disease will likely become
      increasingly common.

PMID- 29588767
TI  - Basic Principles of Health Economics Applied - How to Assess if Transcatheter
      Aortic Valve Implantation is Worth the Investment.
AB  - This article attempts to present some highlights from the rich economic
      literature pertaining to interventional cardiology and transcatheter aortic valve
      implantation (TAVI). There are currently more questions than answers, not
      surprisingly given the pace of technological change in interventional cardiology.
      For clinicians who work in a strictly regulated environment and have limited
      control over their use of medical technologies, this article will hopefully shed
      some light on the motives for policy decisions. For clinicians who make decisions
      on the resources used to treat their patients, it aims to provide the means of
      looking for evidence that will allow for informed decisions from both clinical
      and economic perspectives.

PMID- 29588769
TI  - Foreword.

PMID- 29588768
TI  - No Racial Disparities in the Treatment of ST Elevation Myocardial Infarction - A
      Community-based Experience.
AB  - Whether racial disparities exist in the treatment of ST elevation myocardial
      infarction (STEMI) is not exactly known. We report a retrospective chart review
      of patients with first event of STEMI, in two groups separated by one decade.
      Results revealed that hospital mortality in the 2007 and 1997 groups for African
      Americans versus Caucasians was one of 22 versus 21 of 170, 95 % confidence
      interval (CI) -0.178 to 0.022, p=0.48 and four of 41 versus 39 of 402, 95 % CI 
      0.095 to 0.096, p=1.00, respectively. The mean length of stay (LOS) for African
      Americans and Caucasians in the 2007 and 1997 groups was 5.7 versus 4.1 days
      (p=0.09) and 7.3 versus 6.6 days (p=0.42), respectively. During follow-up, a
      total of 40 patients needed re-intervention in the 2007 group. The re
      intervention rate in African American patients being 13.6 % (three of 22) versus
      21.2 % (36 of 170) in Caucasians, 95 % CI -0.231 to 0.081, with p=0.57. In
      conclusion, there was no evidence of racial disparity in the treatment of STEMI
      in terms of hospital mortality, length of hospital stay and re-intervention rate.

PMID- 29588770
TI  - European Society of Cardiology ST-segment Elevation Myocardial Infarction
      Guidelines in Perspective - Focused on Primary Percutaneous Coronary
      Intervention.
AB  - Patients suffering acute myocardial infarction with ST-segment elevation
      myocardial infarction (STEMI) require full attention of the whole STEMI network
      to save their lives and to improve the quality of life after a heart attack.
      Implementation of the most recent European Society of Cardiology (ESC) and
      American College of Cardiology/American Heart Association (ACC/AHA) STEMI
      Guidelines into the practice is the holy grail of the healthcare systems and all
      stakeholders. In relation to this, the Stent for Life Initiative can serve as one
      of very successful and effective models in Europe and beyond. Although the
      evidence-based approach may be applied to majority of patients, the tailored and
      updated therapy needs to be modified in concordance with the patients' risk
      profile, experience and availability of medical resources. Some 'hot topics',
      issues, differences between the ESC and ACC/AHA Guidelines, latest information
      and perspectives are discussed in this short review; focused on primary
      percutaneous coronary intervention (PCI) as the most effective reperfusion
      therapy.

PMID- 29588771
TI  - The Role of Self-expanding Stents in Patients with Atypical Coronary Anatomy.
AB  - Despite advances with new generation stents, there remains some atypical coronary
      anatomy where optimal stenting continues to be a challenge; such as stent sizing
      in large, ectatic or aneurysmal vessels; tapered vessels; and in vasoconstricted
      arteries such as in ST-segment elevation myocardial infarction or chronic total
      occlusions. Balloon-expandable stents are tubular and cannot easily accommodate
      vessel diameter variations; thrombotic vessels increase the risk of distal
      embolisation and no-reflow; positive remodelling and vasodilation often result in
      subsequent malapposition; and patients with bifurcation lesions have a higher
      risk of adverse events. The STENTYS BMS and DES(P) stents have a self-expanding
      design, which enables a better anatomical fit to the vessel, even with diameter
      variations (up to 6.0 millimetres [mm]), and can adapt to changes in vessel size
      over time. The stents deploy atraumatically from distal to proximal, which could
      reduce distal embolisation and contain disconnectable bridges, which can be
      opened up at a side branch. Self-apposing technology could therefore provide a
      potential solution to current challenges with balloon-expandable stent
      technology.

PMID- 29588772
TI  - Overview of Technical and Cost Considerations in Complex Percutaneous Coronary
      Intervention.
AB  - Complex percutaneous coronary intervention (PCI), encompassing an ever-expanding
      range of challenging lesion sets and patient populations, accounts for a
      significant proportion of PCI procedures being performed currently. Specific
      lesion types associated with lower rates of procedural success and higher rates
      of recurrence or major adverse cardiac events (MACE) include multivessel disease,
      unprotected left main coronary artery disease, fibrocalcific or undilatable
      lesions, chronic total occlusions, degenerated saphenous vein graft lesions,
      thrombotic lesions, and bifurcation disease. Validated tools and technical
      strategies currently exist to address most procedural scenarios encountered and
      should be familiar to the complex PCI operator. Anticipated clinical outcomes,
      projected resource utilization, and cost considerations should all factor into
      the decisions of when, how, and in whom to intervene.

PMID- 29588773
TI  - The Bioresorbable Stent in Perspective-How Much of an Advance is It?
AB  - The novel idea of bioresorbable stent technology continues to fascinate the
      interventional community. This article aims to provide a concise and balanced
      overview of the available technology and clinical evidence. Both potentially
      positive and negative aspects of bioresorbable stents in different lesion subsets
      and clinical situations are discussed.

PMID- 29588774
TI  - Trans-catheter Aortic Valve Implantation Guidelines - Does the Latest Evidence
      Change our Views?
AB  - From the wealth of recent registries and trials scrutinising its performance,
      trans-catheter aortic valve implantation (TAVI) emerges as a viable and rapidly
      established option, both when compared to medical treatment in inoperable
      patients and when compared to conventional surgical treatment in high-risk
      patients. Results consistently demonstrate improvement in functional status and
      outcome; however, appropriate patient selection remains crucial as high-risk
      cohorts become apparent.

PMID- 29588775
TI  - Surgical Approaches to Aortic Valve Replacement and Repair-Insights and
      Challenges.
AB  - Since 1960, surgical aortic valve replacement (sAVR) had been the only effective
      treatment for symptomatic severe aortic stenosis until the recent development of
      transcatheter aortic valve replacement (TAVR). TAVR has offered an alternative,
      minimally invasive treatment approach particularly for patients whose age or co
      morbidities make them unsuitable for sAVR. The rapid and enthusiastic utilization
      of this new technique has triggered some speculation about the imminent demise of
      sAVR. We believe that despite the recent advances in TAVR, surgical approach to
      aortic valve replacement has continued to develop and will continue to be highly
      relevant in the future. This article will discuss the recent developments and
      current approaches for sAVR, and how these approaches will keep pace with
      catheter-based technologies.

PMID- 29588776
TI  - Adoption of Transcatheter Aortic Valve Implantation in Western Europe.
AB  - Transcatheter aortic valve implantation (TAVI) is a novel therapeutic option for
      patients with severe symptomatic aortic stenosis (AS) at excessive or high
      surgical risk for conventional surgical aortic valve replacement. First
      commercialised in Europe in 2007, TAVI growth has been exponential among some
      Western European nations, though recent evidence suggests heterogeneous adoption
      of this new and expensive therapy. Herein, we review the evidence describing the
      utilisation of TAVI in Western Europe.

PMID- 29588777
TI  - Transcatheter Aortic Valve Replacement in Moderate-risk Aortic Stenosis Patients.
AB  - The Placement of Aortic Transcatheter Valves (PARTNER) trial showed the
      effectiveness of transcatheter aortic valve replacement (TAVR) for inoperable
      patients and non-inferiority for mortality versus open valve replacement. There
      are three questions concerning the role of TAVR for intermediate-risk patients.
      These relate to: institutional and surgeon results, physician and hospital
      alignments, and who will pay.

PMID- 29588778
TI  - Percutaneous Paravalvular Leak Closure.
AB  - Symptomatic paravalvular leak (PVL) complicates up to 12 % of surgical valve
      replacements. When patients present with congestive heart failure and/or
      haemolysis, reoperation for repeat valve replacement may be undertaken, but
      presents greater risk and lower likelihood of success than the initial operation.
      Therefore, percutaneous approaches to PVL closure have been developed by
      specialists in structural cardiac intervention. Large series demonstrate high
      levels of procedural success and promising clinical outcomes for this complex
      intervention. A thorough understanding of multimodality imaging is necessary for
      the diagnosis of PVL and the safe and successful performance of these closure
      procedures.

PMID- 29588779
TI  - Transcatheter Mitral Valve Devices - Functional Mechanical Designs.
AB  - Mitral regurgitation is a complex disorder involving a multitude of components of
      the mitral apparatus. With the desire for less invasive treatment approaches,
      transcatheter mitral valve therapies (TMVT) are directed at these components and
      available at varying stages of development. Therapeutic advancements and the
      potential to combine technologies may further improve their efficacy and safety.
      Transcatheter mitral valve replacement, while preserving the mitral apparatus,
      may emerge as an alternative or even a more suitable treatment option. In
      addition, early data on transcatheter mitral valve-in-valve and valve-in-ring
      implantation are encouraging and this approach may be an alternative to
      reoperation in the high-risk patient. This review details the expanding
      functional mechanical designs of current active TMVT.

PMID- 29588781
TI  - Foreword.

PMID- 29588780
TI  - Renal Sympathetic Denervation - A Review of Applications in Current Practice.
AB  - Resistant hypertension is associated with high morbidity and mortality despite
      numerous pharmacological strategies. A wealth of preclinical and clinical data
      have demonstrated that resistant hypertension is associated with elevated renal
      and central sympathetic tone. The development of interventional therapies to
      modulate the sympathetic nervous system potentially represents a paradigm shift
      in the strategy for blood pressure control in this subset of patients. Initial
      first-in-man and pivotal, randomised controlled trials of endovascular, radio
      frequency renal sympathetic denervation have spawned numerous iterations of
      similar technology, as well as many novel concepts for achieving effective renal
      sympatholysis. This review details the current knowledge of these devices and the
      evidence base behind each technology.

PMID- 29588783
TI  - ABSORB BVS Implantation in Bifurcation Lesions - Current Evidence and Practical
      Recommendations.
AB  - The introduction of the ABSORB bioresorbable vascular scaffold (BVS) provides a
      new tool for stenting in interventional cardiology. Initially, relatively simple
      coronary artery lesions were treated with this novel device; nowadays, we are
      gaining clinical experience when treating a wide variety of lesions with the
      ABSORB BVS, including bifurcation lesions. Unfortunately, data are limited in
      terms of the use of the ABSORB BVS in coronary bifurcation lesions, so little is
      known about the safety and feasibility of these procedures. Bench testing and
      case reports showed that single provisional scaffold placement is feasible with
      fenestration of the scaffold towards the side branch and sequential non-compliant
      balloon inflation in the side and main branches. However, no prospective
      randomised clinical data with optical coherence tomography (OCT) imaging for
      different bifurcation stenting techniques are available. Based on the available
      data and our own experience we would recommend the use of the provisional single
      scaffold technique and only to fenestrate the scaffold if a severely pinched
      ostium combined with impaired flow seen on angiogram.

PMID- 29588782
TI  - Risks of Stroke After Coronary Artery Bypass Graft - Recent Insights and
      Perspectives.
AB  - Stroke is one of the most devastating complications after coronary artery bypass
      graft (CABG) surgery, entailing permanent disability, a 3-6 fold increased risk
      of mortality, an incremental hospital resource consumption and a longer length of
      hospital stay. Notwithstanding advances in surgical, anaesthetic and medical
      management across the last 10 years, the risk of stroke after CABG has not
      significantly declined, likely because an older and sicker population is now
      deemed suitable to undergo CABG. The pathogenesis of stroke is multifactorial,
      but two variables are believed to play a major role - cerebral embolisation of
      atheromatous debris arising from the ascending aorta during surgical manipulation
      and hypoperfusion during surgery. Identification of vulnerable patients at
      increased risk of stroke before CABG is of paramount importance for the surgical
      decision-making approach and informed consent. Several models including
      demographic, clinical and procedural variables have been developed to risk
      stratify the hazard of stroke in patients undergoing CABG, but identification of
      severe atherosclerosis of the ascending aorta and pre-existing cerebrovascular
      disease are key determinants for appropriate risk stratification and decision
      making. Atherosclerotic disease of the ascending aorta can be identified before
      surgery using transoesophageal echocardiography, computed tomography and magnetic
      resonance imaging. However, intra-operative ultrasound scanning of the ascending
      aorta is the diagnostic tool with the best sensitivity and specificity for the
      detection of atheromatous debris in the ascending aorta. Although many
      investigators have advocated the use of off-pump CABG to minimise the risk of
      peri-operative stroke, results from randomised trials and meta-analyses have been
      inconsistent. Anaortic approaches, including total arterial revascularisation
      with in situ grafting of both mammary arteries, or the use of the HEARTSTRING(r)
      seal device avoid any manipulation of the aorta, thus potentially minimising the
      risk of stroke in high-risk patients. Assessment and treatment of severe carotid
      artery disease, and aggressive and prompt treatment of post-operative atrial
      fibrillation are other important strategies that should be routinely implemented
      to reduce the risk of stroke in patients undergoing CABG.

PMID- 29588784
TI  - Clinical Impact of Stent Design.
AB  - The introduction and widespread adoption of drug-eluting stents into routine
      clinical practice has seen tremendous changes in the practice of interventional
      cardiology. For a prolonged period, manufacturers have focused research on drugs
      and polymers that are the key to the prevention of in-stent restenosis. However,
      stent platform design and its clinical implications have now come back to the
      fore. This has occurred for numerous reasons, but has primarily been driven by
      the need for modern stents to perform well in increasingly demanding clinical
      scenarios. This paper reviews the historical evolution of stent platform design.
      Current manufacturing processes and materials are also explored. Geometric stent
      construction and its implications for longitudinal stability and the longer term
      risks of stent fracture are reviewed. Finally, the implications of the specific
      stent chosen for different clinical applications including the treatment of
      bifurcations and left main disease are also summarised. This article will
      familiarise cardiologists with the crucial impact of each of these factors on
      modern day practice, as well as acute and long-term outcomes for patients.

PMID- 29588785
TI  - Current Antithrombotic Therapy in Patients with Acute Coronary Syndromes
      Undergoing Percutaneous Coronary Interventions.
AB  - Acute coronary syndromes (ACS) represent a life-threatening complication of the
      systemic atherosclerotic process, affecting the coronary circulation. Thrombosis,
      defined as an uncontrolled activation of the endogenous thrombogenetic reparative
      process, often follows atherosclerotic plaque damage and is mainly engaged by two
      main pathways: platelet aggregation and coagulation. Therefore, antithrombotic
      therapy to modulate either pathway plays an important role for the reduction of
      ischaemic adverse events in ACS patients. Since the advent of aspirin and
      warfarin, numerous antiaggregant and anticoagulant molecules have been developed
      to achieve this goal, but their anti-ischaemic efficacy is often obtained at the
      price of augmented bleedings, which are known to be strong predictors of adverse
      outcome. This article briefly reviews the physiopathological mechanisms of
      thrombosis and presents an overview of the available literature supporting the
      use of these major drugs, as well as the European Society of Cardiology
      recommendations for their utilisation in the setting of non-ST and ST-elevation
      myocardial infarction undergoing invasive treatment.

PMID- 29588786
TI  - Use of Thrombectomy Devices in Primary Percutaneous Interventions for ST
      elevation Myocardial Infarction - An Update.
AB  - Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion
      modality in patients with ST-elevation myocardial infarction (STEMI). While PPCI
      is highly effective in achieving epicardial coronary reperfusion, a significant
      proportion of patients fail to achieve adequate myocardial reperfusion. This is
      in part due to the distal microembolisation of thrombus and plaque debris during
      PCI. Recognition of this has led to the development of a number of devices with
      different mechanisms of action that aim to reduce such distal embolisation and
      therefore improve end myocardial perfusion. Study results of thrombectomy devices
      however have been largely inconsistent, especially about clinical outcome data,
      and several meta-analyses have been carried out as a result. This review aims to
      critically analyse the literature data on thrombectomy during PPCI, taking into
      account the most recent studies and the latest meta-analyses looking to see
      whether thrombectomy use is associated with improved outcomes.

PMID- 29588788
TI  - Review of Data and Discussion - Who Should Undergo Patent Foramen Ovale Closure
      in 2014?
AB  - A patent foramen ovale is a relatively common finding in the general population
      and is associated with a number of conditions, including cryptogenic stroke. In
      2014, percutaneous patent foramen ovale (PFO) closure is a frequently performed
      procedure; the bulk of these procedures being carried out for secondary
      prevention of cryptogenic stroke, along with other indications, such as
      prevention of decompression illness, platypnoea-orthodeoxia syndrome and
      migraine. Of these conditions the largest body of evidence available is for
      cryptogenic stroke and there is ongoing debate of the benefit of PFO closure over
      medical therapy. This article will review the available evidence of PFO closure
      in each of these contexts, with a particular focus on randomised controlled
      trials, and endeavour to outline in whom the evidence suggests closure should be
      considered.

PMID- 29588787
TI  - Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive
      Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disorder
      characterised by left ventricular hypertrophy. A subgroup of patients develops
      limiting symptoms in association with left ventricular outflow tract obstruction
      (LVOTO). Current international guidelines recommend that symptomatic patients are
      initially treated by alleviating exacerbating factors and negatively inotropic
      medication. Drug-refractory symptoms require a comprehensive evaluation of the
      mechanism of LVOTO and review by a multidisciplinary team to consider the
      relative merits of myectomy, alcohol septal ablation (ASA) and pacing. This
      article provides a brief overview of HCM and the pathophysiology of LVOTO, and
      reviews the use of ASA in patients with drug-refractory symptoms secondary to
      LVOTO.

PMID- 29588789
TI  - Differences in Outcomes and Indications between Sapien and CoreValve
      Transcatheter Aortic Valve Implantation Prostheses.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a suitable
      alternative to surgical valve replacement for patients with severe, symptomatic,
      calcified aortic stenosis and a background of co-morbidities, which can make
      surgery a high-risk option. It has also evolved as an alternative for
      degenerative prosthetic heart valve disease. Since the inception of TAVI in 2002,
      the two main devices in routine clinical use are the Edwards Sapien valve (since
      2006) and the Medtronic CoreValve (since 2007). The more recent Sapien XT valve
      and Sapien 3 have been in clinical use since 2010 and 2013, respectively. In
      addition to registry data on these devices, there are a number of completed and
      ongoing randomised controlled trials, including one comparing the two devices.
      The aim of this article is to discuss the differences in indications and outcomes
      between these two prostheses.

PMID- 29588790
TI  - Transcatheter Aortic Valve Replacement and Left Atrial Appendage Occlusion - A
      Stitch in Time?
AB  - Many patients have now been able to receive transcatheter aortic valve
      replacement (TAVR) therapy for severe aortic stenosis. These patients have atrial
      fibrillation and are placed on warfarin for stroke prophylaxis. The opportunity
      for treatment with left atrial appendage occlusion (LAAO) in place of warfarin
      for this population exists, especially for those with increased bleeding risk.
      This paper discusses the prevalence and aetiology of stroke in patients
      presenting for TAVR (with a focus on the risk from chronic and acute atrial
      fibrillation) and also the benefit of LAAO closure in this population.

PMID- 29588791
TI  - Transcatheter Aortic Valve Implantation Without General Anaesthetic.
AB  - Transcatheter aortic valve implantation (TAVI) procedures are increasingly being
      performed under local anaesthetic, generally with sedation. Operators hope this
      will reduce mortality, morbidity and length of hospital stay. A general
      anaesthetic (GA), however, although involving intrinsic risk, permits
      transoesophageal echocardiogram (TOE) imaging throughout a procedure as well as
      eliminating patient anxiety, pain and movement. This article reviews the
      published literature, all single-centre experiences, comparing TAVI procedures
      performed with and without a GA. Procedures performed without GA are generally
      shorter with reduced length of stay compared with those performed under GA. There
      is no evidence of any difference in outcomes.

PMID- 29588792
TI  - Foreword.

PMID- 29588793
TI  - Fractional Flow Reserve Derived from Coronary Imaging and Computational Fluid
      Dynamics.
AB  - The assessment of functional severity of atherosclerotic stenoses in patients
      with coronary artery disease by invasive fractional flow reserve (FFR)
      measurement requires coronary artery cannulation, advancement of a wire and
      intravenous adenosine infusion with inherent procedure-related risk and costs.
      Coronary computed tomographic angiography (CCTA) and rotational coronary
      angiography (RA) have been recently used in conjunction with computational fluid
      dynamics (CFD) and image-based modelling for the determination of FFR without the
      need for additional imaging, modification of acquisition protocols or
      administration of medication. FFR derived from CCTA was demonstrated as superior
      to measures of CCTA stenosis severity for determination of lesion-specific
      ischaemia. Estimation of FFR from RA images and CFD provides a less invasive
      alternative to conventional FFR measurement while estimated values are in
      agreement with measured values. These new, combined anatomic-functional
      assessments have the potential to simplify the noninvasive diagnosis of coronary
      artery disease with a single study to identify patients with ischaemia-causing
      stenosis who may benefit from revascularisation.

PMID- 29588794
TI  - Intravascular Ultrasound-based Imaging Modalities for Tissue Characterisation.
AB  - Atherosclerosis is the leading cause of cardiovascular mortality and morbidity in
      the developed world. Intravascular ultrasound (IVUS) is a widely used imaging
      modality providing complementary diagnostic information to angiography regarding
      the vessel wall of the coronary arteries. IVUS has been used for assessment of
      ambiguous angiographic lesions, evaluation of new interventional devices and in
      atherosclerosis progression-regression trials. However, the standard gray-scale
      IVUS has limited value for the accurate identification of specific plaque
      components. This limitation has been partially over- come by introduction of new
      IVUS-based imaging methods such as: virtual histology IVUS, iMAP-IVUS and
      Integrated Backscatter IVUS. These methods utilise the ultrasound backscatter
      signal to enable a more detailed characterization of plaque morphology or tissue
      characterization and to provide insight on the features of vulnerable plaque.

PMID- 29588795
TI  - Impact of Intravascular Ultrasound in Clinical Practice.
AB  - Intravascular ultrasound (IVUS) has expanded our understanding of atherosclerotic
      plaque morphology, and provides an opportunity to guide cardiovascular
      interventions and evaluate results. Use of this technique requires understanding
      of ultrasound physics, catheter differences, skills in vessel, plaque and stent
      quantification and knowledge of artifacts and various physiologic and pathologic
      findings. Optimal cardiovascular interventions should result in absence of inflow
      or outflow obstruction, precise geographic landing, while attaining the largest
      feasible luminal gain without plaque protrusion, vessel dissection or perforation
      and, if deployed, with complete stent expansion and apposition to the vessel
      wall. IVUS is safe, cost efficient and effectively optimises cardiovascular
      interventions. In addition, IVUS improves outcomes when used to guide coronary
      interventions using bare metal stents (BMS) and drug eluting stents (DES). The
      role of IVUS in endovascular therapy is rapidly expanding. This review will focus
      on the impact of IVUS in clinical practice.

PMID- 29588796
TI  - Optimum Utilisation of Novel Antiplatelet Agents in Clinical Practice.
AB  - Prasugrel and ticagrelor are two novel promising antiplatelet agents inhibiting
      the platelet activation via the adenosine diphosphate pathway. Both achieve a
      faster, more intense, and more consistent platelet inhibition than clopidogrel.
      Both novel antiplatelet agents have demonstrated superiority over clopidogrel in
      large, randomised controlled trials in patients with acute coronary syndrome
      (ACS). Prasugrel may be best suited for younger patients with planned
      percutaneous coronary intervention and large areas of myocardium at risk or
      diabetes mellitus who have a low risk of bleeding. The benefits of prasugrel
      relative to clopidogrel in ACS must be weighed against the increase in the risk
      of bleeding associated with its use. Ticagrelor may be the best option for
      patients with ACS without T elevations, elderly patients or patients managed
      conservatively. Vorapaxar, a new oral protease-activated-receptor 1 antagonist,
      may be a good option for secondary prevention in patients with stable
      atherosclerosis and no history of stroke.

PMID- 29588797
TI  - MGuard Embolic Protection Stent - The Importance of Thrombus Management in ST
      elevation Myocardial Infarction Primary Percutaneous Coronary Intervention:
      Proceedings of STEMI symposium at EuroPCR on 20-23rd May 2014 in Paris.
AB  - Distal embolisation of atherothrombotic material is a frequent consequence of
      percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction
      (STEMI). This causes microvascular occlusions, leading to a further reduction in
      myocardial reperfusion. The MGuardTM embolic protection stent (EPS) features a
      unique polymer micronet mesh coating. When used in acute STEMI, the MGuard EPS
      shows significant improvement in myocardial flow and ST resolution, even in
      complicated clinical cases vs the standard approach with conventional bare metal
      or drug-eluting stents. Data from the andomised Safety and Efficacy Study of
      MGuard Stent After a Heart Attack (MASTER II) trial and from a real-life registry
      have shown the efficacy and safety of the MGuard in primary PCI. This report of
      the proceedings of a symposium at EuroPCR, 20-23 May 2014, Paris, France,
      discussed clinical trial data, as well as a number of clinical cases,
      illustrating the utility of the MGuard EPS in difficult situations.

PMID- 29588798
TI  - Bioresorbable Scaffolds.
AB  - Percutaneous coronary intervention (PCI) has undergone major advances including
      the evolution in stent technology, from bare metal stents (BMS), to their drug
      eluting counterparts, to the development of bioresorbable scaffolds (BRS). The
      primary notion of BRS was to facilitate complete vascular healing and restore
      normal endothelial function following the resorption of stent scaffold while
      providing equivalent mechanical properties of a metallic drug eluting stents
      (DES) in the earlier stages. BRS provide attractive physiologic advancements over
      the existing DES and have shown promising results in initial clinical studies
      albeit with small sample sizes. Their use has been primarily restricted to
      patients recruited in clinical trials with limited real-world applicability.
      Thus, data from larger randomised control trials is awaited. The major objective
      of this article is to review the evidence on BRS and identify their clinical
      applicability in current interventional practice.

PMID- 29588799
TI  - Cre8TM Unique Technology in Challenging Daily Practice: Proceedings of a
      satellite symposium held at EuroPCR on 20th - 23rd May 2014 in Paris.
AB  - The use of drug-eluting stents (DES) has improved clinical outcomes in
      percutaneous coronary intervention (PCI) procedures. However, first-generation
      DES were associated with safety concerns arising from the persistence of durable
      polymers, including late stent thrombosis. The Cre8TM DES is a novel polymer-free
      stent designed to overcome these issues. In a presentation at EuroPCR 2014, two
      clinical cases were discussed. The first was a case of high bleeding risk; the
      second was the case of multivessel disease with a significant risk of stent
      restenosis. Together, these cases illustrated the complexity of decision-making
      in PCI in daily practice. In both cases, the Cre8TM DES offered a safe and
      effective solution to these challenging cases.

PMID- 29588800
TI  - Meeting the Unmet - The Cre8 Polymer-free Drug-eluting Stents Technology:
      Proceedings of a satellite symposium held at EuroPCR on May 20th - 23rd 2014 in
      Paris.
AB  - The use of first-generation drug-eluting stents (DES) has been associated with
      safety concerns such as very late stent thrombosis. Today, with the release of
      newer DES, there is a need for comparative studies of percutaneous coronary
      intervention (PCI) versus coronary artery bypass grafting (CABG) to demonstrate
      their value in patients with high risk of restenosis such as diabetic patients.
      In a satellite symposium presented at EuroPCR 2014, the Cre8TM DES was discussed.
      The Cre8 device has a number of unique clinical features, including polymer-free
      technology, abluminal reservoir technology and bio-inducer surface that ensure
      effective neointima suppression and rapid endothelialisation. The efficacy of the
      Cre8 DES has been demonstrated in the International randomised comparison between
      DES Limus Carbostent and Taxus drug-eluting stents in the treatment of de novo
      coronary lesions (NEXT) randomised clinical study, with equivalent efficacy in
      the diabetic and general populations, a unique finding. Ongoing clinical studies
      such as Investig8 and the Tel Aviv Medical Center (TLVMC) Cre8 study have
      confirmed the efficacy of the device in patient populations with a high
      proportion of diabetic patients. The Demonstr8 randomised trial has shown almost
      complete Cre8 strut coverage at three months with a numerical advantage versus
      bare metal stent (bare metal stents [BMS] - comparator device) at one month. In
      addition, use of the Cre8 DES may enable a shorter duration of dual antiplatelet
      therapy (DAPT) following PCI. The Cre8 DES therefore represents a significant
      advance in stent technology and may be particularly useful in challenging
      clinical settings.

PMID- 29588801
TI  - Evidence for Benefit of Percutaneous Coronary Intervention for Chronically
      Occluded Coronary Arteries (CTO) - Clinical and Health Economic Outcomes.
AB  - Percutaneous revascularisation of a coronary chronic total occlusion (CTO)
      remains one of the technical frontiers of interventional cardiology. CTOs are
      common, and yet intervention is only attempted in 10 % of cases. CTO procedures
      are perceived to be technically challenging, lengthy, associated with significant
      risk and have only limited data to support the practise. Recent technical
      advances have dramatically increased the success rate, shortened procedural time
      and improved clinical outcomes. The aim of this article is to critically examine
      the data that supports CTO intervention, including specifically an appraisal of
      procedural safety, benefit and overall cost effectiveness.

PMID- 29588802
TI  - Percutaneous Treatment of Coronary Chronic Total Occlusions Part 1: Rationale and
      Outcomes.
AB  - Coronary chronic total occlusions (CTOs) are commonly encountered in patients
      with coronary artery disease. Compared to patients without coronary CTOs, those
      with CTO have worse clinical outcomes and lower likelihood of complete coronary
      revascularisation. Successful CTO percutaneous coronary intervention (PCI) can
      significantly improve angina and improve left ventricular function. Although
      currently unproven, successful CTO PCI might also reduce the risk for arrhythmic
      events in patients with ischaemic cardiomyopathy, provide better tolerance of
      future acute coronary syndrome, and possibly improve survival. Evaluation by a
      heart team comprised of both interventional and non-interventional cardiologists
      and cardiac surgeons is important for determining the optimal revascularisation
      strategy in patients with coronary artery disease and CTOs. Ad hoc CTO PCI is
      generally not recommended, so as to allow sufficient time for (a) discussion with
      the patient about the indications, goals, risks, and alternatives to PCI; (b)
      careful procedural planning; and (c) contrast and radiation exposure
      minimisation. Use of drug-eluting stents is recommended for CTO PCI, given the
      lower rates of angiographic restenosis compared to bare metal stents.

PMID- 29588803
TI  - Percutaneous Treatment of Coronary Chronic Total Occlusion Part 2: Technical
      Approach.
AB  - Dual injection is recommended for nearly all chronic total occlusion (CTO)
      percutaneous coronary intervention (PCI) to determine the optimal crossing
      strategy and guide wire advancement into the distal true lumen. Strategies that
      provide enhanced guide catheter support (such as long sheaths, large-bore guiding
      catheters, use of guide catheter extensions, and anchor techniques) are important
      for maximising the success rate and efficiency of CTO PCI. Use of a microcatheter
      or over-the-wire balloon is strongly recommended in CTO PCI for enhancing the
      penetrating power of the guidewire, enabling change in tip shape and allowing
      guidewire change (stiff CTO guidewires are not optimal for crossing non-occluded
      coronary segments). Adherence to a procedural strategy that standardises CTO
      technique and facilitates procedural success is recommended. Such a strategy
      would permit stepwise decision-making for antegrade and retrograde methods;
      inform guidewire selection; and incorporate alternative approaches for instances
      of initial failure. Given the paucity of long-term outcomes with use of novel
      crossing techniques (antegrade dissection/re-entry and retrograde), antegrade
      wire escalation is the preferred CTO crossing technique, if technically feasible.
      Using measures to minimise radiation exposure (including but not limited to use
      of 7.5 frames per second fluoroscopy and use of low magnification) and contrast
      administration is recommended. CTO PCI is best performed at centres with
      dedicated CTO PCI experience and expertise. Use of crossing difficulty prediction
      tools, such as the J-CTO score, can facilitate the selection of cases with a high
      likelihood of quick crossing that can be attempted at less experienced centres.

PMID- 29588804
TI  - New Advances in Chronic Total Occlusions.
AB  - Coronary chronic total occlusions (CTOs) still represent the greatest technical
      challenge that interventional cardiologists face. CTOs remain seriously
      undertreated with percutaneous techniques, far below their prevalence. One reason
      for the low uptake was the suboptimal CTO percutaneous coronary intervention
      (PCI) success rates over a long period of time. During the last years, dedicated
      groups of experts in Japan, Europe and United States fostered the development and
      standardisation of modern CTO recanalisation techniques, along with providing
      focused training and proctorship worldwide. As a result, dedicated operators
      achieved success rates far beyond 90 %, while coping with lesions of increasing
      complexity. A series of studies, mainly retrospective and observational in
      nature, explored the prognostic impact of CTO PCI, revealing that successful
      lesion recanalisation is related to improved patient outcome and anginal status;
      further evidence from randomised trials is on the way. The following review
      reports on the most recent advances in the field of CTO recanalisation, in an
      attempt to promote a more balanced approach in patients with chronically occluded
      coronary arteries and encourage more operators to cope with these inherently
      complex lesions.

PMID- 29588805
TI  - Contemporary Techniques for Coronary Chronic Total Occlusions Revascularisation:
      Sharing Experience in a Global World: Proceedings of a satellite symposium held
      at EuroPCR on May 20th - 23rd 2014 in Paris Katrina Mountfort, Medical Writer,
      Radcliffe Cardiology.
AB  - Chronic total occlusions (CTO) are the most challenging lesions treated by
      interventional cardiologists. A symposium at EuroPCR 2014 discussed factors
      influencing the success of percutaneous intervention (PCI) in CTO. Current
      treatment paradigms suggest that one or two vessel disease should be treated by
      PCI while three-vessel disease requires surgery if complete revascularisation
      cannot be achieved with PCI. In patients with CTO and multi-vessel disease timing
      is key, and evidence of ischaemic burden and expected completeness of
      revascularisation is required before PCI is undertaken. Other factors affecting
      procedural success include the available equipment and expertise of the operator.
      Flexiblity in strategy selection is also important as it is frequently necessary
      to switch strategies during the procedure. The presentation included two live
      cases that illustrated the complexity of this procedure.

PMID- 29588806
TI  - Identifying and correcting epigenetics measurements for systematic sources of
      variation.
AB  - Background: Methylation measures quantified by microarray techniques can be
      affected by systematic variation due to the technical processing of samples,
      which may compromise the accuracy of the measurement process and contribute to
      bias the estimate of the association under investigation. The quantification of
      the contribution of the systematic source of variation is challenging in datasets
      characterized by hundreds of thousands of features.In this study, we introduce a
      method previously developed for the analysis of metabolomics data to evaluate the
      performance of existing normalizing techniques to correct for unwanted variation.
      Illumina Infinium HumanMethylation450K was used to acquire methylation levels in
      over 421,000 CpG sites for 902 study participants of a case-control study on
      breast cancer nested within the EPIC cohort. The principal component partial R
      square (PC-PR2) analysis was used to identify and quantify the variability
      attributable to potential systematic sources of variation. Three correcting
      techniques, namely ComBat, surrogate variables analysis (SVA) and a linear
      regression model to compute residuals were applied. The impact of each correcting
      method on the association between smoking status and DNA methylation levels was
      evaluated, and results were compared with findings from a large meta-analysis.
      Results: A sizeable proportion of systematic variability due to variables
      expressing 'batch' and 'sample position' within 'chip' was identified, with
      values of the partial R2 statistics equal to 9.5 and 11.4% of total variation,
      respectively. After application of ComBat or the residuals' methods, the
      contribution was 1.3 and 0.2%, respectively. The SVA technique resulted in a
      reduced variability due to 'batch' (1.3%) and 'sample position' (0.6%), and in a
      diminished variability attributable to 'chip' within a batch (0.9%). After ComBat
      or the residuals' corrections, a larger number of significant sites (k = 600 and
      k = 427, respectively) were associated to smoking status than the SVA correction
      (k = 96). Conclusions: The three correction methods removed systematic variation
      in DNA methylation data, as assessed by the PC-PR2, which lent itself as a useful
      tool to explore variability in large dimension data. SVA produced more
      conservative findings than ComBat in the association between smoking and DNA
      methylation.

PMID- 29588807
TI  - Placental surface area mediates the association between FGFR2 methylation in
      placenta and full-term low birth weight in girls.
AB  - Background: Fibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of
      the fibroblast growth factor receptor family. FGFR2 gene expression is associated
      with the regulation of implantation process of placenta which plays a vital role
      in fetal growth. DNA methylation is widely known as a mechanism of fetal growth.
      However, it is unclear whether and how DNA methylation of FGFR2 gene in the
      placenta is associated with full-term low birth weight. This case-control study
      aims to explore the links between FGFR2 methylation in placenta and full-term low
      birth weight and to further examine the mediation effect of placental surface
      area on this association. Results: We conducted analyses for each of the five
      valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and
      found that per one standard deviation increase in the DNA methylation of CpG 11
      at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight
      (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in
      placental surface area (beta = - 0.18; standard error = 0.08, p = 0.02). The
      mediation effect of placental surface area on the association between DNA
      methylation and full-term low birth weight was significant in girls (OR = 1.38,
      95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was
      48.38%. Conclusion: Our findings suggested that placental surface area mediated
      the association between DNA methylation of FGFR2 in placenta and full-term low
      birth weight in a sex-specific manner. Our study supported the importance of
      placental epigenetic changes in placental development and fetal growth.

PMID- 29588808
TI  - Physiologically based microenvironment for in vitro neural differentiation of
      adipose-derived stem cells.
AB  - The limited capacity of nervous system to promote a spontaneous regeneration and
      the high rate of neurodegenerative diseases appearance are keys factors that
      stimulate researches both for defining the molecular mechanisms of
      pathophysiology and for evaluating putative strategies to induce neural tissue
      regeneration. In this latter aspect, the application of stem cells seems to be a
      promising approach, even if the control of their differentiation and the
      maintaining of a safe state of proliferation should be troubled. Here, we focus
      on adipose tissue-derived stem cells and we seek out the recent advances on the
      promotion of their neural differentiation, performing a critical integration of
      the basic biology and physiology of adipose tissue-derived stem cells with the
      functional modifications that the biophysical, biomechanical and biochemical
      microenvironment induces to cell phenotype. The pre-clinical studies showed that
      the neural differentiation by cell stimulation with growth factors benefits from
      the integration with biomaterials and biophysical interaction like microgravity.
      All these elements have been reported as furnisher of microenvironments with
      desirable biological, physical and mechanical properties. A critical review of
      current knowledge is here proposed, underscoring that a real advance toward a
      stable, safe and controllable adipose stem cells clinical application will derive
      from a synergic multidisciplinary approach that involves material engineer, basic
      cell biology, cell and tissue physiology.

PMID- 29588810
TI  - Increased frequency of angina attacks caused by switching a brand-name
      vasodilator to a generic vasodilator in patients with vasospastic angina: Two
      case reports.
AB  - It is well known that calcium channel blockers (CCBs) are the first line of
      therapy for vasospastic angina (VSA). Here, we report two cases of VSA with an
      increase in the frequency of angina attacks after switching from a brand-name to
      a generic CCB. In both cases, angina recurred upon switching from a brand-name
      CCB to a generic CCB during follow-up. The patients' condition improved upon
      switching back to the original CCB. Both cases involved a high severity of VSA,
      based on the results of spasm provocation testing. These findings suggest that,
      in some patients with severe VSA, the frequency of angina attacks increases when
      switching from a brand-name CCB to a generic CCB. Cardiologists should consider
      this factor when prescribing drugs for angina.

PMID- 29588809
TI  - Evolution of transanal total mesorectal excision for rectal cancer: From top to
      bottom.
AB  - The gold standard for curative treatment of locally advanced rectal cancer
      involves radical resection with a total mesorectal excision (TME). TME is the
      most effective treatment strategy to reduce local recurrence and improve survival
      outcomes regardless of the surgical platform used. However, there are associated
      morbidities, functional consequences, and quality of life (QoL) issues associated
      with TME; these risks must be considered during the modern-day multidisciplinary
      treatment for rectal cancer. This has led to the development of new surgical
      techniques to improve patient, oncologic, and QoL outcomes. In this work, we
      review the evolution of TME to the transanal total mesorectal excision (TaTME)
      through more traditional minimally invasive platforms. The review the
      development, safety and feasibility, proposed benefits and risks of the
      procedure, implementation and education models, and future direction for research
      and implementation of the TaTME in colorectal surgery. While satisfactory short
      term results have been reported, the procedure is in its infancy, and long term
      outcomes and definitive results from controlled trials are pending. As evidence
      for safety and feasibility accumulates, structured training programs to
      standardize teaching, training, and safe expansion will aid the safe spread of
      the TaTME.

PMID- 29588811
TI  - Effect of low dose aspirin and dipyridamole on primary patency of arteriovenous
      grafts in hemodialysis patients: a randomized double-blind placebo-controlled
      trial.
AB  - Background: There is some evidence for the efficacy of antiplatelet therapies in
      increasing the vascular access patency duration or decreasing the thrombosis of
      arteriovenous grafts. Objective: To determine the effect of low dose aspirin and
      dipyridamole on primary patency of arteriovenous grafts in hemodialysis patients.
      Methods: This randomized, double-blind, placebo-controlled trial was done at Imam
      Reza Hospital in Mashhad, Iran from September 10, 2015 to July 05, 2016. Sixty
      hemodialysis patients, after the placement of a new arteriovenous graft, were
      divided into three study groups which including; Group 1, who received 80 mg
      aspirin tablet daily, Group 2 received 80 mg aspirin plus 75 mg dipyridamole
      daily and Group 3 received placebo daily. Primary unassisted patency was recorded
      in follow-up until 12 months and the outcomes were analysed using one-way ANOVA
      test. Results: Primary patency time in Group 1 (Aspirin) was 324.75+/-147.00 day
      and for Group 2 (Aspirin + Dipyridamole) was 399.05+/-92.09 day and for Group 3
      (Placebo) was 383.55+/-108.23 day. There were no significant differences between
      the 3 groups (p>0.05). Successful dialysis was done in 16.7% in Group 1, 37.5% in
      Group 2 and 45% in Group 3 from brachial arteriovenous grafts after 1-year follow
      up (p=0.746). Conclusions: In treating dialysis patients, treatment with low dose
      aspirin and dipyridamole is not effective on increasing the synthetic grafts
      primary patency duration. Trial registration: The trial was registered at the
      Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the Trct id:
      TCTR20160920003. Funding: The authors received no financial support for the
      research, authorship, and/or publication of this article.

PMID- 29588812
TI  - Efficacy of mummy on healing of pressure ulcers: A randomized controlled clinical
      trial on hospitalized patients in intensive care unit.
AB  - Background: Mummy is a mineral substance which according to Persian medicine
      texts, may be useful in treatment of chronic ulcers. Objective: The present study
      was performed with the aim of determining the effect of mummy on healing of
      pressure in male patients who had been hospitalized due to cerebrospinal injury
      in the Intensive Care Unit. Methods: This randomized, placebo-controlled clinical
      trial was performed on 75 patients who had pressure ulcer at Shahid Bahonar
      Hospital in Kerman, Iran, from September 2016 to March 2017. The control group
      received normal saline and routine wound dressing, while the intervention group
      received mummy water solution 20% in addition to normal saline and routine wound
      dressing on a daily basis. Data was recorded based on the PUSH method. In both
      groups, ulcers were evaluated on days 0, 7, 14, 21 and 28 for the variables of
      ulcer surface area, the amount of exudate and type of tissue. Data analysis was
      done through SPSS 21 and using t-test, Repeated Measure Analysis, Cox Regression
      and Chi-square. Results: Both groups showed reduction in the average ulcer
      surface area (3.26 to 0.53 in the intervention group and 5.1 to 3.46 in the
      control group), the average exudate amount (1.26 to 0.26 in the intervention
      group and 1.83 to 1.06 in the control group) and the average tissue score (1.36
      to 0.23 in the intervention group and 2.13 to 1.26 in the control group). Over
      the entire study period, the intervention group showed more acceptable signs of
      healing compared to the control group (p<0.05). Conclusion: The healing process
      was more prominent in the intervention group than the control group. Clinical
      trial registration: The trial was registered at the Iranian Registry of Clinical
      Trials with registered NO. (IRCT2014042917494N1) (29/04/2014). Funding: No
      financial support for the research.

PMID- 29588813
TI  - Lead concentration in the muscles of slaughtered buffalos in northwest regions of
      Iran.
AB  - Background: The topic of food safety has become a major public health issue
      worldwide. Over recent decades, the growing concern for food safety has brought
      about greater research regarding the risks associated with the consumption of
      produce that has been contaminated by pesticides, heavy metals and/or toxins.
      Objective: The study was conducted to determine the concentration of Pb in the
      muscle of buffalos slaughtered in the northwest regions of Iran (Ardabil, Urmia
      and Tabriz cities). Methods: The present was a descriptive cross-sectional study
      in the northwest regions of Iran during 2013 to 2014. A total of 30 muscle
      samples from individual buffalos were analyzed for Pb concentrations using Atomic
      Absorption Spectrophotometer (ASS). Statistical analysis was performed using SPSS
      17.0. All results were computed as mean standard deviation and subjected to one
      way analysis of variance to establish whether the differences in Pb
      concentrations in meat samples from different cities were significant or not. The
      Statistical significance was determined at p<0.05. Results: The results showed
      that the mean concentration of Pb in muscle samples were measured 0.043+/-0.035
      ppm. The highest Pb concentration (0.11 ppm) was detected in the buffalo muscle
      samples from Urmia city. In total, 25 muscle samples (80.33%) were contaminated
      with Pb and concentration of Pb in 3.33% of contaminated samples exceeded the
      permissible limits advised by the European Commission (EC) (0.1 ppm). Conclusion:
      We recommend identifying Pb sources in order to eliminate or control Pb
      contamination of food, and monitor environmental exposures and hazards to prevent
      lead poisoning.

PMID- 29588814
TI  - Environmental interventions based on the Health Belief Model and the Ecological
      social model in the continuation of consumption of rice, free from toxic metals.
AB  - Background and aim: Continuation of healthy nutritional behaviors is one of the
      important factors in effectiveness of educational intervention programs. The aim
      of this research is to compare the Health Belief Model and the Ecological-social
      model in reducing consumption of rice contaminated with toxic metals after
      completion of environmental intervention and continuation of consumption of
      healthy rice. Methods: This research was the implementation of a six-month
      randomized controlled trial interventional program in two groups' interventions
      along with a control group, with 80 people for each group totally, amounting to
      240 women, between 18 and 50 years of age in Ilam, Iran in 2014. The
      questionnaires of the three groups consisted of demographic information,
      knowledge, the constructs of the models, performance of rice consumption.
      Friedman test and repeated measures used for data analysis with SPSS (version
      20), and confidence interval of 95% were considered. Results: The results of the
      Friedman test indicated a significant increase in the number of women consuming
      healthy rice over six months after intervention in both intervention groups
      (p<0.001). Women in the ECO group consumed healthy rice 27.5% more than the HBM
      group (p<0.001). The results of repeated measures analysis of variance suggested
      greater improvement in the consumption of healthy rice in the ECO group in
      comparison with the HBM group over six months after intervention (p<0.05).
      Conclusions: Both educational environmental intervention methods caused the
      altered diet of people regarding consumption of healthy rice over six months
      after the intervention. Increased social support also probably had a more
      effective role in continuation of healthy diet among the people.

PMID- 29588815
TI  - Students' attitudes towards impact of the health department website on their
      health literacy in Semnan University of Medical Sciences.
AB  - Background and aim: Health literacy has been of interest to policymakers because
      of its impact on health decision-making as one of the important issues for
      promoting community health and improving the quality of health care delivery.
      Therefore, it seems necessary to examine the status of the website of the health
      sector of the University of Medical Sciences in promoting health literacy from
      the viewpoint of the students. Methods: This cross-sectional study was performed
      on 529 medical and allied students in schools affiliated to Semnan University of
      Medical Sciences, Semnan, Iran between 2016 and 2017. In this study, a valid and
      reliable adult health literacy questionnaire designed by Montazeri et al. was
      used. The questionnaire was distributed among students in medical and allied
      health schools and they were asked to complete the questionnaire. Independent
      samples t-test, one-way ANOVA, and Pearson product-moment correlation were used
      to analyze data by SPSS 19. Results: Mean scores of the participants' attitudes
      towards reading of health information was 3.14 and towards decision and usage of
      health information was 2.53. Relationship between the study subjects' demographic
      characteristics and their attitudes was significant (p<0.05). Conclusion: This
      study showed that interventional strategies are necessary to lead students to
      make effective use of the university's health department website. Hence, the
      results of this study showed that the website of the health department needs to
      be redesigned, and this design would allow a better link between the University
      of Medical Sciences and its audience to promote health literacy.

PMID- 29588816
TI  - Designing and psychoanalysis: A comprehensive questionnaire on coping with
      domestic violence against women in Iranian society.
AB  - Background: Domestic violence is the third sociopathology after addiction and
      child abuse in Iran. Fifty-six percent of Iranian women in the range of 17-32
      years old are exposed to the highest domestic violence. Objective: The aim of
      this study was to design and psychoanalyze a comprehensive questionnaire on
      coping with domestic violence against women in Iranian society. Methods: This
      study was carried out on a random sample of women exposed to domestic violence
      and referred to the health and care center of Shahid Beheshti University of
      Medical Sciences in Tehran, and Forensic Medical Centers in Urmia city (Iran), in
      2017. Two hundred questionnaires were distributed among the participants. One
      hundred sixty-eight questionnaires were returned to the researchers for data
      analysis. Eight of those were excluded from the analysis because of
      incompleteness. Finally, exploratory factor analysis was performed. Results:
      After reviewing the literature, a questionnaire with 32 items was developed.
      Content validity ratio (0.95) and content validity index (0.97) were obtained.
      The results of exploratory factor analysis indicated that the questionnaire
      explained 69.34% of the data variance. Cronbach's alpha coefficient, and test
      retest methods were used for determining the reliability and the obtained value,
      which were 0.82 and 0.81, respectively. Conclusion: Validity and reliability of
      the questionnaire with 32 items were confirmed. The tool can be utilized to
      measure how women cope with domestic violence.

PMID- 29588817
TI  - Social media; resolving tunnel vision in practicing medicine.
AB  - Background: With the emergence of social media, physicians who use social media,
      including emergency medicine physicians, have shared their experiences with their
      colleagues instead of working alone and keeping their experiences to themselves.
      Objective: This study aimed to evaluate the rate and type of use of electronic
      online sources and social media, in order to improve learning and education among
      emergency medicine residents. Methods: This was a cross-sectional study carried
      out from September 2015 until August 2016 on emergency medicine residents of two
      main medical universities of Tehran, Iran. A questionnaire was prepared by
      reviewing the existing studies and asking emergency medicine professors inside
      and outside Iran for opinions. Census sampling method was applied and all
      emergency medicine residents were included. The gathered data were analyzed using
      statistical tests of chi square, Independent-samples t-test and Pearson's
      correlation coefficient via SPSS version 21. Results: Seventy three residents
      with the mean age of 34.2+/-5.2 years participated in this study (60.3% female).
      Smart phone is the most important tool they use for connecting to the Internet.
      About 30% use the Internet for about 1-2 hours a day. In half of these
      participants less than 25% of this time is spent on something related to their
      academic field of study. The correlation of sex (p=0.034) and age (p=0.049) with
      extent of using social media related to the academic field of study were
      significant. Other analytical analyses were not statistically significant
      (p>0.05). Conclusion: In summary, the findings of current study showed that
      despite sufficient access to proper technology, use of social media and online
      sources by high majority of the studied EM residents regarding improvement of
      their learning and educational level is very limited.

PMID- 29588818
TI  - A study of the diagnostic value of Inhibin A Tests for occurrence of preeclampsia
      in pregnant women.
AB  - Background: Hypertensive disorders are common during pregnancy, and are among 3
      important causes of maternal death. Preeclampsia occurs in 3 to 5% of
      pregnancies. Early diagnosis of this disorder can lead to better pregnancy
      outcomes. Objective: The aim of this study was to determine the relationship
      between inhibin A serum levels during second stage pregnancy screening tests, and
      incidence and severity of preeclampsia. Methods: In this study, 300 pregnant
      women who referred to Kowsar Hospital and carried out second stage pregnancy
      screening tests from September 2014 to March 2015 in Urmia city, Iran, were
      enrolled. Five ml venous blood samples were obtained from each participant, and
      inhibin A serum levels were evaluated in all cases. Finally, all the necessary
      information was obtained from the pregnancy files of participants after delivery,
      and gathered in a questionnaire. The data were analyzed using SPSS software
      version 18 and independent t-test, ANOVA and descriptive statistics were used. P
      values less than 0.05 were considered significant. Results: Among the 300
      pregnant women who were studied, the gestational age at the time of acquiring
      blood samples was as follows: 169 cases (56.3%) at 16-17 weeks, 77 cases (25.7%)
      at 18-19 weeks and 14 cases at 20 weeks (4.7%). In this study, MOM of inhibin A
      was more than 1.25 in 12 cases that finally, preeclampsia occurred in them. This
      relationship was statistically significant (p=0.001). The relationship between
      MOM of inhibin A and severe preeclampsia was evaluated, and the relationship was
      significant (p=0.004). The relationship between MOM of inhibin A and pregnancy
      hypertension was not significant (p=0.643). Conclusion: Considering the results
      of this study, we can conclude that MOM of inhibin A levels in maternal serum
      during second stage pregnancy screening tests can predict incidence and severity
      of developing preeclampsia in pregnant women. This is not true in cases of
      pregnancy hypertension.

PMID- 29588819
TI  - An agent based architecture for high-risk neonate management at neonatal
      intensive care unit.
AB  - Background: In recent years, the use of new tools and technologies has decreased
      the neonatal mortality rate. Despite the positive effect of using these
      technologies, the decisions are complex and uncertain in critical conditions when
      the neonate is preterm or has a low birth weight or malformations. There is a
      need to automate the high-risk neonate management process by creating real-time
      and more precise decision support tools. Objective: To create a collaborative and
      real-time environment to manage neonates with critical conditions at the NICU
      (Neonatal Intensive Care Unit) and to overcome high-risk neonate management
      weaknesses by applying a multi agent based analysis and design methodology as a
      new solution for NICU management. Methods: This study was a basic research for
      medical informatics method development that was carried out in 2017. The
      requirement analysis was done by reviewing articles on NICU Decision Support
      Systems. PubMed, Science Direct, and IEEE databases were searched. Only English
      articles published after 1990 were included; also, a needs assessment was done by
      reviewing the extracted features and current processes at the NICU environment
      where the research was conducted. We analyzed the requirements and identified the
      main system roles (agents) and interactions by a comparative study of existing
      NICU decision support systems. The Universal Multi Agent Platform (UMAP) was
      applied to implement a prototype of our multi agent based high-risk neonate
      management architecture. Results: Local environment agents interacted inside a
      container and each container interacted with external resources, including other
      NICU systems and consultation centers. In the NICU container, the main identified
      agents were reception, monitoring, NICU registry, and outcome prediction, which
      interacted with human agents including nurses and physicians. Conclusion:
      Managing patients at the NICU units requires online data collection, real-time
      collaboration, and management of many components. Multi agent systems are applied
      as a well-known solution for management, coordination, modeling, and control of
      NICU processes. We are currently working on an outcome prediction module using
      artificial intelligence techniques for neonatal mortality risk prediction. The
      full implementation of the proposed architecture and evaluation is considered the
      future work.

PMID- 29588820
TI  - Determinant of successful implementation of Computerized Provider Order Entry
      (CPOE) system from physicians' perspective: Feasibility study prior to
      implementation.
AB  - Background: Health information technology is a solution for medical error
      reduction through the implementation of Computerized Provider Order Entry (CPOE).
      Objective: The aim of this study was to determine physicians' attitudes toward
      the implementation of CPOE. Methods: This cross-sectional study was started in
      March 2017 and completed in June 2017. The study used a questionnaire to collect
      data from physicians in hospitals affiliated to Urmia University of Medical
      Sciences. We invited 200 physicians who were not using a CPOE system.
      Questionnaires were randomly distributed among physicians. In order to understand
      the physicians' attitude about implementation the CPOE system, we used the
      Diffusion of Innovation Theory, developed by E.M. Rogers. Data were analyzed by
      SPSS version 16.0, using descriptive statistics and one-way ANOVA. A p value
      <0.05 was considered to be statistically significant. Results: Most of the
      physicians were women (n=54, 60%) and the average age of the physicians was
      36.39+/-8.42 years. About three-quarters of the physicians (76.66%) reported that
      they found the CPOE system adapted to their specific professional practice. The
      relative advantage of the CPOE system was estimated to be 42.22% for physicians
      and the complexity of that was 13.33%. There was no significant relationship
      between Compatibility, Relative advantages and Complexity with physicians'
      experience in HIS use and physicians' degree of education (p>0.05). Conclusion:
      Since the role of CPOE systems is very important in hospitals in order to reduce
      medication errors and to improve the quality of care, our results can be used to
      assist the planning and introduction of CPOE systems.

PMID- 29588821
TI  - Serum level of vitamin D in preterm infants and its association with premature
      related respiratory complications: a case-control study.
AB  - Background and aim: Prematurity and related problems, especially respiratory
      distress, are one of the main challenges for neonatal medicine. The aim of this
      study was to compare vitamin D levels in preterm infants with, and those without
      respiratory distress. Methods: This case-control study was conducted in Ghaem and
      Emam Reza Hospitals in Mashhad (Iran) from 2015 to 2016. In this study, we
      examined 160 preterm infants weighing less than 2000 grams and born at less than
      34 weeks' gestation. Serum vitamin D levels were measured in preterm infants
      without- and those with respiratory distress, and their mothers. Neonatal
      characteristics, including age, sex, birth weight, gestational age, Apgar score
      and needs for oxygen, resuscitation, ventilation and surfactant were documented.
      The data were analyzed using SPSS version 16.0. Results: Means serum level of
      maternal vitamin D in control and case groups were 16.66+/-14.29 ng/dl and
      21.23+/-15.19 ng/dl, respectively (p=0.029). In addition, mean serum level of
      neonatal vitamin D in control and case groups were 11.69+/-8.66 ng/dl 17.9+/
      12.55 ng/dl, respectively (p=0.001). Vitamin D levels in premature neonates
      without respiratory distress and their mothers were significantly different from
      other preterm neonates with respiratory distress (p=0.029). There was a direct
      correlation with neonatal and maternal vitamin D levels (r=0.713, p=0.001). The
      duration of hospitalization (p=0.001), gestational age (p=0.073), birth weight
      (p=0.001), one- and (p=0.001) five-minute (p=0.001) Apgar scores and head
      circumference (p=0.002) had significant relation with vitamin D levels in
      neonates. Death (12.5%) and pneumothorax (7.5%) were the main complications among
      cases with respiratory distress. Conclusion: According to the results of present
      research, neonatal vitamin D levels have a significant association with
      respiratory distress syndrome and maternal vitamin D levels.

PMID- 29588822
TI  - Candida albicans endophthalmitis following penetrating keratoplasty: A case
      report.
AB  - Endophthalmitis is one of the most serious complications of intraocular
      surgeries, and Candida albicans constitutes the majority of cases of post
      penetrating keratoplasty (PK) endophthalmitis. The presenting case is a 21-year
      old woman with known case of advanced keratoconus and vernal keratoconjunctivitis
      who underwent PK, and developed recalcitrant anterior uveitis and subsequent
      whitish lesion on the superonasal of the lens. She was on topical steroids with
      possible impression of Uretts Zavalia syndrome versus phacoantigenic uveitis
      following traumatic cataract up to the 50th day of post operation that manifested
      symptoms of frank endophthalmitis; and underwent deep vitrectomy, lensectomy,
      localized iridectomy and irrigation with diluted Imipenem and Amphotericin-B.
      Microbiologic study of a vitreous sample revealed growth of Candida albicans,
      however optisol culture was negative and donor rim was not evaluated. One week
      later, intravitreal Amphotericin-B was administered. The patient remained aphakic
      with clear graft in the 6th month follow up. Due to great correlation of positive
      donor rim culture with fungal endophthalmitis and the devastating effect of
      delayed diagnosis, routine donor rim culture is recommended, to aid us in earlier
      diagnosis in the presence of nonspecific early signs of fungal endophthalmitis.

PMID- 29588823
TI  - Histological evaluation of orthodontic tooth movement following low level laser
      irradiation in rabbits.
AB  - Background: Reduction of orthodontic treatment time is a major concern for
      orthodontists. Low level laser therapy (LLL) has been widely used in dentistry
      and it has been claimed that it could stimulate bone formation. Objective: The
      aim of the present study was to evaluate histological effects of LLL on alveolar
      bone remodeling during experimental tooth movement in rabbits. Methods: In this
      experimental study which was performed in the animal lab of Mashhad Dental School
      in 2016 twenty pre-pubertal female albino rabbits with the mean age of 8+/-1
      weeks were randomly assigned into two groups. All the rabbits were examined by a
      veterinarian, and underweight or diseased rabbits were excluded from the study.
      Fifty gram orthodontic force was applied via 0.014 stainless steel spring on
      central teeth in both groups. In the first group, low level laser KLO3 (wave
      length: 980 nm, Power: 80mw) was irradiated three minutes from the buccal aspect
      of central teeth for 21 days. In the second group, rabbits were not exposed to
      laser irradiation and served as our control group. After this period, the
      distance between mesial corners of incisors was measured blindly by a caliper
      calibrated as 0.1mm. All rabbits in both groups were sacrificed by vital
      perfusion for histological evaluation to determine the number of resorption
      lacuna and amount of fibrous tissue. Independent sample t-test was used to
      analyze the data. Results: The number of resorption lacuna, the rate of tooth
      movement and fibrous tissue were significantly greater in the lased group
      (p=0.05). Conclusion: Low level laser irradiation could accelerate tooth movement
      in rabbits via increased resorptive activity in alveolar bone.

PMID- 29588824
TI  - The status and predictors of hypertension preventive nutritional behaviors in
      adolescents based on the constructs of the Theory of Planned Behavior.
AB  - Background: Malnutrition is an important factor affecting hypertensive incidence.
      Since the unhealthiest nutritional behaviors are rooted in childhood attitudes
      and experiences, applying educational interventions to these age groups will be
      most useful in the formation of preventive nutritional behaviors. Objective: To
      determine the predictive power of the TPB on hypertension in junior high-school
      students. Methods: The present cross-sectional study was conducted on 160 junior
      high-school students in Kashmar, Iran in academic year commencing 2-13-2014,
      selected through random sampling. The participants completed a researcher-made
      questionnaire consisting of a demographic information form and a section to
      evaluate the constructs of the TPB. The data collected were analyzed in SPSS-16
      using the correlation Wilcoxon statistics test, the one-way ANOVA and multiple
      linear regression analysis. Results: The mean age of the students was 13.51. A
      total of 47% of the students had snacked on potato chips and cheese puffs, 45%
      had eaten high-fat foods and 51.2% had eaten cookies and chocolates within the
      past week. The variable of behavioral intention predicted 32% of the variations
      in preventive nutritional behaviors by itself. The Pearson product-moment
      correlation analysis found that hypertension preventive nutritional behaviors
      were significantly correlated with attitude (p<0.001, r=0.38), perceived
      behavioral control (p<0.001, r=0.38), and behavioral intention. Moreover,
      significant correlations were observed between subjective norms and attitude
      (p<0.028, r=0.173), perceived behavioral control and attitude (p<0.003, r=0.231),
      behavioral intention and attitude (p<0.001, r=0.370), behavioral intention and
      subjective norms (p<0.030, r=0.171) and between behavioral intention and
      perceived behavioral control (p<0.001, r=0.484). Conclusion: The examined
      students revealed an adequate adherence to preventive nutritional behaviors.
      Nutrition education interventions should be developed based on variables such as
      behavioral intention and its determinants, i.e. attitude, perceived behavioral
      control and subjective norms.

PMID- 29588825
TI  - The impact of general health and social support on health promoting lifestyle in
      the first year postpartum: the structural equation modelling.
AB  - Background and aim: Postpartum is a critical period for mothers which often leads
      to neglect of their own health. Mothers' new responsibilities may affect their
      health promoting lifestyle (HPL). The aim of this study was to determine the
      impact of both general health and social support on health-promoting lifestyle.
      Methods: A cross-sectional survey was conducted on 310 women who gave birth over
      a one-year period in Zanjan (Iran), 2016. A proportionate stratified random
      sampling technique was used to select respondents from each stratum. Health
      promoting lifestyle was assessed using the health-promoting lifestyle profile II
      (HPLP II) scale. A structure equation model (SEM) was used to determine the
      relationship between observed and latent variables. Data were analysed using SPSS
      version 22 and LISREL 8.5 software. Results: The age of 42.6% of the participants
      was more than 30 years and 40.3% of them had an academic education. The mean
      score of the health-promoting lifestyle was 131.28 (15.37). The structural
      equation model fitted well with RMSEA =0.07, CFI=0.92, and GFI=0.94. Among the
      latent factors, general health, with a factor load of -0.68, had greater impact
      on health-promoting lifestyle than social support. Moreover, there was a
      significant correlation (-0.63) between general health and perceived social
      support in the postpartum period. Conclusion: health-promoting lifestyle was not
      at appropriate levels among women in the first year after delivery. These
      findings suggest that strengthening general health and social support would
      improve a health-promoting lifestyle in Iranian postpartum women.

PMID- 29588826
TI  - Relationship between behavioral indices of pain during labor pain with pain
      intensity and duration of delivery.
AB  - Background: Certain behaviors can be adopted by women to cope with labor pain
      according to their individual characteristics, which are currently called
      behavioral indicators during labor pain, and include facial expressions, verbal
      expressions, tone of voice, body movements, degree of relaxation, and respiratory
      system functioning during delivery. Moreover, severity of pain and duration of
      labor can vary due to several factors including individual characteristics.
      Objective: The purpose of the present study was to determine the relationship
      between behavioral indicators during labor pain, severity of pain, and delivery
      duration. Methods: In this cross-sectional study, 120 low risk pregnant women who
      referred to Omolbanin (AS) Hospital in the city of Mashhad (Iran) for delivery in
      2014, were selected via convenience sampling method, which was then followed by
      completion of demographic information forms. From cervical dilatation of 3-5
      centimeters until delivery, the Labor Pain Coping Behavior Observation Form
      (comprised of 6 sub-groups of facial expressions, verbal expressions, tone of
      voice, body movements, degree of relaxation, and respiratory function and
      severity and duration of pain) was completed during uterine contractions and
      every half an hour. Using the Inventory of Labor Information; vital signs,
      frequency of contractions, and duration of the first and second stages of labor
      were measured. Furthermore, the content validity of the questionnaire was
      determined and its reliability was confirmed by Cronbach's alpha method. Then,
      the data were analyzed using the SPSS version 16, through Pearson Product-Moment
      Correlation and Spearman's Rank-Order Correlation, Kruskal-Wallis test, and
      ANOVA. Results: According to the results, 16.2% of the individuals had
      undesirable behavioral indicators during labor pain, 50% of them were endowed
      with acceptable behaviors, and 33.8% of these women had desirable behaviors. The
      findings also revealed that the duration of the active phase of the first stage
      of labor (p<0.001 and r=-0.453), the duration of the second stage of labor
      (p<0.012 and r=-0.146), and the severity of pain (p<0.001 and r=-0.450) were
      significantly and inversely correlated with behavioral indicators during labor
      pain; i.e. an increase in the mean score of behavioral indicators during labor
      pain could lead to a decline in the duration of stages of labor and severity of
      pain. Conclusion: It was concluded that behaviors demonstrated by women in labor
      had effects on their pains in the course of delivery, and there was also a
      relationship between the duration of stages of labor and its severity of pain.
      Therefore, it was recommended to turn attention to behaviors by women in labor in
      order to achieve a desirable clinical management.

PMID- 29588827
TI  - Genetic association of liver X receptor beta rs2695121 polymorphism with obesity
      related traits in a northeastern Iranian population.
AB  - Background: Liver X receptor Beta (LXRbeta), located in an obesity susceptible
      region, has been shown to be involved in the metabolism of lipid and
      carbohydrates. Previous human genetic studies have suggested genetic variability
      of LXRbeta could be associated with human obesity. Therefore, we hypothesized
      that LXRbeta gene rs2695121 polymorphism may be associated with the risk of
      obesity in a northeastern Iranian population. Methods: A TaqMan allelic
      discrimination assay was used to genotype LXRbeta rs2695121 polymorphism in this
      cross-sectional study of 168 obese, 209 overweight and 76 normal-weight subjects
      recruited from Mashhad city in Iran. Logistic regression analyses were used to
      analyze alleles and genotypes distribution. Anthropometrics and clinical
      variables among different genotype carriers were compared by univariate analyses.
      All statistical analysis was performed using SPSS v.16.0. Results: Allelic and
      genotypic associations with obesity were not significant for the rs2695121
      variant even after adjustment for age and gender (OR=1.17, 95% CI=0.46-2.91),
      p=0.586). Moreover, haplotype analysis using data from the other variant
      (rs17373080) of LXRbeta revealed no significant association (p=0.88). However,
      among the clinical and metabolic parameters tested, systolic and diastolic blood
      pressures were found nominally associated with the genotype CT (p=0.031 and
      p=0.017 respectively). Conclusion: This study failed to demonstrate any
      association between the rs2695121 variant of LXRbeta and obesity neither alone
      nor when considered with rs17373080. However, its association with blood pressure
      may influence one's susceptibility to obesity, supporting further studies in a
      larger population.

PMID- 29588828
TI  - The effects of health promotion model-based educational program on self-care
      behaviors in patients undergoing coronary artery bypass grafting in Iran.
AB  - Background and aim: Post-operative self-care behaviors, have positive effects on
      increase in adaptability, and reduce cardiac surgery patients' disability. The
      present study is carried out aimed at determining the effect of education based
      on a health promotion model on the patients' self-care behaviors after coronary
      artery bypass surgery. Methods: This is a semi-experimental study carried out in
      Mazandaran (Iran) in 2016. Two hundred and twenty patients who participated in
      the study were selected using a simple random sampling method from a population
      of postoperative patients, and divided into control and experimental groups (110
      patients in each) using block (AABB) randomization. Self-designed self-care
      questionnaires based on a health promotion model were distributed among the
      patients once before and three months after intervention. The data were analyzed
      by SPSS-22, Chi-Square tests, Mann-Whitney and ANCOVA at the significance level
      of p<0.05. Results: The average score of total self-care behaviors in cardiac
      surgery patients was not significant between the two groups before education
      (p=0.065), but after training, a significant difference was observed between the
      two groups (p<0.001). The analysis of ANOVA with repeated measure indicated that
      following the intervention, significant difference was observed between the two
      groups in terms of improvement of self-care behaviors after excluding the effect
      of pre-test and controlling demographic and health-related characteristics.
      Conclusions: Developing and implementing a training program based on the health
      promotion model can enhance self-care behaviors and reduce the number of
      admissions in patients after cardiac surgery.

PMID- 29588829
TI  - The effectiveness of clinical teaching of mental health courses in nursing using
      clinical supervision and Kirkpatrick's model.
AB  - Background: Clinical experience associated with the fear and anxiety of nursing
      students in the psychiatric unit. Mental health nursing instructors find it
      challenging to teach nursing students to deal with patients with mental disorders
      in an environment where they need to provide patient teaching and clinical
      decision-making based on evidence and new technology. Objective: To measure the
      effectiveness of clinical teaching of mental health courses in nursing using
      clinical supervision and Kirkpatrick's model evaluation in the psychiatry unit of
      Imam Reza Hospital, Bojnurd, Iran. Methods: This cross-sectional study was
      carried out from 2011 to 2016 on 76 nursing students from a university as part of
      a clinical mental health course in two semesters. The students were selected by a
      non-probable convenient sampling method. After completing their clinical
      education, each student responded to checklist questions based on the four-level
      Kirkpatrick's model evaluation and open questions relating to clinical
      supervision. Finally, all data was analyzed using the SPSS version 16. Results:
      The students have evaluated clinical supervision as a useful approach, and
      appreciated the instructor's supportive behavior during teaching and imparting
      clinical skills. This has made them feel relaxed at the end of the clinical
      teaching course. In addition, in the evaluation through Kirkpatrick's model, more
      than 70% of the students have been satisfied with the method of conducting the
      teaching and average score of nursing students' attitude toward mental health
      students: Their mean self-confidence score was 18.33+/-1.69, and the mean score
      of their performance in the study was evaluated to be 93.74+/-5.3 from 100
      points. Conclusion: The results of clinical mental health teaching through
      clinical supervision and Kirkpatrick's model evaluation show that the
      satisfaction, self-esteem, attitude, and skill of nursing students are excellent,
      thereby portraying the effectiveness of clinical teaching. But this program still
      needs to be reformed. To establish long-term goals and obtain knowledge and
      clinical skills of nursing, it is recommended to develop a curriculum and
      evaluate it appropriately.

PMID- 29588830
TI  - Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis and non
      cystic fibrosis bronchiectasis.
AB  - Background: Aspergillus sensitization (AS) and allergic bronchopulmonary
      aspergillosis (ABPA) can occur as a cause of permanent lung damage in patients
      with cystic fibrosis (CF) and non-CF bronchiectasis. Objective: The aim of this
      study was to determine the frequency of AS and ABPA in patients with CF and non
      CF bronchiectasis in southwestern Iran. Methods: This cross-sectional study was
      conducted on 33 patients with CF and 27 patients with non-CF bronchiectasis from
      southwestern Iran who were referred to Namazi Hospital affiliated to Shiraz
      University of Medical Sciences from July 2015 to February 2016. Skin prick test
      to Aspergillus fumigatus, peripheral blood eosinophil count, total serum IgE,
      specific IgE and IgG against Aspergillus fumigatus as well as radiologic chest
      studies were done for each patient. Statistical analysis was done by Mann-Whitney
      U test, Fisher Exact test, and Kappa weighted in SPSS software version 18. Level
      of significance was set at p<0.05. Results: Nine patients with CF (27.3%) and one
      patient with non-CF bronchiectasis (3.7%) had positive skin tests to Aspergillus.
      There was 81.2% agreement between positive skin test and specific IgE to
      Aspergillus fumigatus (p<0.001). Three patients with CF (9%) met the diagnostic
      criteria for ABPA, whereas ABPA was not seen in patients with non-CF
      bronchiectasis. Conclusion: ABPA was low in this study, considering more
      frequency of AS in patients with cystic fibrosis, clinicians should keep in mind
      the diagnosis of ABPA for those CF patients that do not respond to usual medical
      therapy and have positive skin tests to Aspergillus allergens.

PMID- 29588832
TI  - Testing, testing.

PMID- 29588831
TI  - Analysis of the expression pattern of the schizophrenia-risk and intellectual
      disability gene TCF4 in the developing and adult brain suggests a role in
      development and plasticity of cortical and hippocampal neurons.
AB  - Background: Haploinsufficiency of the class I bHLH transcription factor TCF4
      causes Pitt-Hopkins syndrome (PTHS), a severe neurodevelopmental disorder, while
      common variants in the TCF4 gene have been identified as susceptibility factors
      for schizophrenia. It remains largely unknown, which brain regions are dependent
      on TCF4 for their development and function. Methods: We systematically analyzed
      the expression pattern of TCF4 in the developing and adult mouse brain. We used
      immunofluorescent staining to identify candidate regions whose development and
      function depend on TCF4. In addition, we determined TCF4 expression in the
      developing rhesus monkey brain and in the developing and adult human brain
      through analysis of transcriptomic datasets and compared the expression pattern
      between species. Finally, we morphometrically and histologically analyzed
      selected brain structures in Tcf4-haploinsufficient mice and compared our
      morphometric findings to neuroanatomical findings in PTHS patients. Results: TCF4
      is broadly expressed in cortical and subcortical structures in the developing and
      adult mouse brain. The TCF4 expression pattern was highly similar between humans,
      rhesus monkeys, and mice. Moreover, Tcf4 haploinsufficiency in mice replicated
      structural brain anomalies observed in PTHS patients. Conclusion: Our data
      suggests that TCF4 is involved in the development and function of multiple brain
      regions and indicates that its regulation is evolutionary conserved. Moreover,
      our data validate Tcf4-haploinsufficient mice as a model to study the
      neurodevelopmental basis of PTHS.

PMID- 29588835
TI  - Challenging current views on bile acid diarrhoea and malabsorption.
AB  - Background: In 2012, the National Institute for Health and Care Excellence (NICE)
      assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also
      known as SeHCAT) for the investigation of diarrhoea due to bile acid
      malabsorption (BAM) in patients with IBS-D and in patients with Crohn's disease
      who have not had an ileal resection. NICE concluded that tauroselcholic
      (75selenium) acid was recommended for use in research only. NICE will be
      reviewing the decision to update the guidance for tauroselcholic (75selenium)
      acid, for these populations, in March 2017. Aim: Our aim is to summarise advances
      in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re
      evaluate their understanding of this disorder. Approach: We review the
      prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence
      available since the original NICE review in 2012, and discuss the economic issues
      associated with failure to diagnose or to treat BAD/BAM accurately. Evidence
      update: There is new and compelling evidence available since DG7, which shows
      that tauroselcholic (75selenium) acid scanning is a powerful tool in the
      diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1%
      prevalence in the UK, as suggested by clinical practice diagnosis rates), and
      highlight that the true prevalence of BAD/BAM could be far greater than this.
      Conclusion: We present evidence that challenges current opinion about this
      disorder, and we commend both clinicians and health technology assessment (HTA)
      agencies for being open to arguments and new evidence in any future HTAs.

PMID- 29588834
TI  - Practical guidance on the use of faecal calprotectin.
AB  - Differentiation between inflammatory bowel disease (IBD) and functional gut
      disorders, and the determination of mucosal disease activity in established cases
      of IBD remain the cornerstones of disease diagnosis and management. Non-invasive,
      accurate biomarkers of gut inflammation are needed due to the variability of
      symptoms, the inaccuracies of currently available blood markers and the cost and
      invasive nature of endoscopy. Numerous biomarkers have been used and/or
      considered with some in current use. This article reviews the current evidence
      base around the indications for using biomarkers and their limitations, with a
      particular focus on faecal calprotectin.

PMID- 29588836
TI  - Emerging role of thalidomide in the treatment of gastrointestinal bleeding.
AB  - Thalidomide was initially synthesised in 1954 and marketed as a sedative and
      antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation
      that it was teratogenic with over 10 000 children born with congenital
      abnormalities. Since then it has been used for treatment of dermatological and
      oncological conditions, including myeloma. In 1994, it was found to have a potent
      antiangiogenic effect via downregulation of vascular endothelial growth factor
      (VEGF). This has led to its use in gastrointestinal bleeding, as vascular
      abnormalities such as angiodysplasia have been found to have elevated VEGF
      levels. This article will review the current evidence of the use of thalidomide
      in bleeding associated with gastrointestinal vascular malformations, including
      angiodysplasia, gastric cancer and radiation-induced proctitis.

PMID- 29588837
TI  - Nasal unsedated seated percutaneous endoscopic gastrostomy (nuPEG): a safe and
      effective technique for percutaneous endoscopic gastrostomy placement in high
      risk candidates.
AB  - Objective: Percutaneous endoscopic gastrostomy (PEG) tube placement is associated
      with a high risk of cardiorespiratory complications in patients with significant
      respiratory compromise. This study reports a case series of high-risk patients
      undergoing PEG placement using a modified technique-nasal unsedated seated PEG
      (nuPEG) placement. Design: Retrospective review of 67 patients at high risk of
      complications undergoing PEG placement between September 2012 and December 2016.
      Setting: UK specialist tertiary centre for clinical nutrition support.
      Interventions: Patients underwent 'push' PEG placement using nasal endoscopy
      without sedation in a seated position. Main outcome measures: Procedural success
      and tolerability, short term (within 24 hours), medium term (24 hours to 30 days)
      complications and survival were recorded. Results: 67 patients underwent 68 nuPEG
      placements. The majority had motor neuron disease (46/67). One patient developed
      a lower respiratory tract infection the following day. Two patients experienced
      accidental displacement of their PEG within 2 weeks. One patient died within 30
      days of nuPEG insertion due to reasons unrelated to the procedure. Endoscopic
      comfort scores of 1 or 2 (98.0%) indicated good tolerance. A failure rate of
      10.5% was attributed to intrathoracic displacement of the stomach, almost
      certainly due to the advanced stage of the neurological disease and associated
      diaphragmatic weakness. Conclusions: Our experience with the nuPEG technique
      suggests that it is safe and well tolerated in high-risk patients. As a result,
      it has now entirely supplanted radiologically inserted gastrostomy insertion in
      our institution and we recommend it as the method of choice for gastrostomy tube
      insertion in such patients.

PMID- 29588838
TI  - The clinical management of hereditary haemochromatosis.
AB  - Hereditary haemochromatosis is an autosomal recessive disorder with variable
      penetrance. Most patients are C282Y homozygotes while heterozygotes or patients
      who are homozygous with other mutations are uncommonly affected. The true
      genotype to phenotype expression remains unclear. Treatment with phlebotomy is
      highly effective and cost-efficient while liver transplantation confers a
      curative option.

PMID- 29588839
TI  - Non-invasive markers of liver fibrosis in fatty liver disease are unreliable in
      people of South Asian descent.
AB  - Objective: Liver biopsy is the most accurate method for determining stage and
      grade of injury in non-alcoholic fatty liver disease (NAFLD). Given risks and
      limitations of biopsy, non-invasive tests such as NAFLD fibrosis score, aspartate
      transaminase (AST) to platelet ratio index, Fib-4, AST/alanine transaminase ratio
      and BARD are used. Prevalence and severity of NAFLD and metabolic syndrome vary
      by ethnicity, yet tests have been developed in largely white populations. We
      tested our hypothesis that non-invasive tests that include metabolic parameters
      are less accurate in South Asian compared with white patients. Design:
      Retrospective cross-sectional. Setting: Specialist liver centre. Patients:
      Patients with histologically confirmed NAFLD. Interventions: Scores calculated
      using clinical data taken within 1 week and compared with histology (Kleiner).
      Main outcome measures: Diagnostic test characteristics. Results: 175 patients
      were identified. South Asians (n=90) were younger, had lower body mass index and
      lower proportion of obesity compared with white patients (n=79), with comparable
      rates of diabetes and liver injury. Tests are less sensitive at detecting
      advanced fibrosis in South Asian compared with white patients. Relative risk of
      correct diagnosis in white patients compared with South Asians is 1.86 (95% CI
      1.4 to 2.6). In binary logistic regression models, ethnicity and platelet count
      predicted accuracy. Transient elastography was equally and highly accurate in
      both ethnicities. Conclusions: Blood test-based non-invasive scores are less
      accurate in South Asian patients, irrespective of metabolic parameters. Ethnicity
      should be considered when devising risk-stratification algorithms for NAFLD.

PMID- 29588840
TI  - Device-assisted enteroscopy in the UK: description of a large tertiary case
      series under conscious sedation.
AB  - Objective: Device-assisted enteroscopy (DAE) has developed rapidly, particularly
      with the advent of double-balloon enteroscopy (DBE). This study reports a case
      series from a UK tertiary centre for DAE across two modalities-DBE and spiral
      enteroscopy (SE)-under conscious sedation. Design: Retrospective observational
      study of 257 enteroscopy procedures from 2008 to 2014. Data were collected on
      demographics, indications, diagnosis, sedation requirements, duration,
      complications, tolerance, therapy performed and completion rate. Procedures were
      performed under conscious sedation using a combination of midazolam, pethidine
      and fentanyl in a solely outpatient setting. Results: Obscure gastrointestinal
      bleeding (OGIB) was the commonest indication for DAE (n=164, 63.8%). Overall,
      yield of DAE was 47.2% and varied significantly across the indications (p=0.003).
      There was a greater likelihood of positive findings if the indication was
      polyposis syndrome (75%), abnormal capsule endoscopy (67%) or OGIB (53%) and in
      older patients (mean age normal exam 60.3 vs abnormal exam 67.9 years, p<0.001).
      Higher mean doses of midazolam were used for DBE from above (5.4 mg, SD 2.24) and
      SE (5.6 mg, SD 2.9) to DBE from below (4.4 mg, SD 1.8). No serious complications
      were recorded. Tolerance of DAE was good with the majority (240/257, 93.4%) of
      procedures tolerated with comfort scores 0 or 1. Therapy was performed in 121/257
      (47.1%) of procedures. The strongest predictor indications for therapy to be
      performed at DAE were abnormal capsule endoscopy (88.9%) and occult
      gastrointestinal (GI) bleeding (54.9%). Completion rates were higher in DBEb
      (91.8%) compared to DBEa (76.5%) and SE (81.6%). Conclusion: DAE under conscious
      sedation is safe and well tolerated. DAE has a high yield if performed for
      recognised indications and may be safely used to provide therapy where a
      diagnosis has been made using other modalities.

PMID- 29588841
TI  - Non-technical skills and gastrointestinal endoscopy: a review of the literature.
AB  - Background: Non-technical skills (NTS) have gained increasing recognition in
      recent years for their role in safe, effective team performance in healthcare.
      Gastrointestinal endoscopy is a procedure-based specialty with rapidly advancing
      technology, significant operational pressures and rapidly changing 'teams of
      experts'. However, to date there has been little focus on the effect of NTS in
      this field. Objectives: This review aims to examine the existing literature on
      NTS in gastrointestinal endoscopy and identify areas for further research.
      Method: A systematic search of MEDLINE, Embase, Cochrane Library, PsychINFO,
      CINAHL Plus and PubMed databases was performed using search terms Non-Technical
      Skills, Team Performance or Team Skills, and Endoscopy, Colonoscopy, OGD,
      Gastroscopy, Endoscopic Retrograde Cholangio-Pancreatography or Endoscopic
      Ultrasound. Results: Eighteen relevant publications were found. NTS are deemed an
      essential component of practice, but so far there is little evidence of their
      integration into training or competency assessment. Those studies examining the
      effects of NTS and team training in endoscopy are small and have variable outcome
      measures with limited evidence of improvement in skills or clinical outcomes. NTS
      assessment in endoscopy is in its early phases with a few tools in development.
      Conclusions: The current literature on NTS in gastrointestinal endoscopy is
      limited. NTS, however, are deemed an essential component of practice, with
      potential positive effects on team performance and clinical outcomes. A validated
      reliable tool would enable evaluation of training and investigation into the
      effects of NTS on outcomes. There is a clear need for further research in this
      field.

PMID- 29588842
TI  - Factors associated with the efficacy of polyp detection during routine flexible
      sigmoidoscopy.
AB  - Objective: Flexible sigmoidoscopy reduces the incidence of colonic cancer through
      the detection and removal of premalignant adenomas. However, the efficacy of the
      procedure is variable. The aim of the present study was to examine factors
      associated with the efficacy of detecting polyps during flexible sigmoidoscopy.
      Design and patients: Retrospective observational cohort study of all individuals
      undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from
      January 2013 to January 2016. Results: A total of 7713 patients were included.
      Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%)
      patients. On multivariate analysis, increasing age (OR 1.020 (1.016-1.023)
      p<0.001), male sex (OR 1.23 (1.10-1.38) p<0.001) and the use of any bowel
      preparation (OR 3.55 (1.47-8.57) p<0.001) were associated with increasing numbers
      of polyps being detected. There was no significant difference in the number of
      polyps found in patients who had received an oral laxative preparation compared
      with an enema (OR 3.81 (1.57-9.22) vs 3.45 (1.43-8.34)), or in those who received
      sedation versus those who had not (OR 1.00 vs 1.04 (0.91-1.17) p=0.591).
      Furthermore, the highest number of polyps was found when the sigmoidoscope was
      inserted to the descending colon (OR 1.30 (1.04-1.63)). Conclusions: Increasing
      age, male sex and the utilisation of any bowel preparation were associated with
      an increased polyp detection rate. However, the use of sedation or oral laxative
      preparation appears to confer no additional benefit. In addition, the results
      indicate that insertion to the descending colon optimises the efficacy of
      flexible sigmoidoscopy polyp detection.

PMID- 29588843
TI  - Protracted severe systemic cytomegalovirus disease in an immunosuppressed patient
      with ulcerative colitis.
AB  - A 33-year-old man with ulcerative colitis presented with 5-day history of fever,
      night sweats, abdominal pain and increased stool frequency. He was on mesalazine
      M/R 1 g once daily, 6-mercaptopurine (6-MP) 75 mg once daily and prednisolone 40
      mg once daily. Examination revealed fever and tachycardia. Blood examinations
      identified a persistent leucopenia, C reactive protein of 23 mg/L and an initial
      alanine transaminase of 855 IU/L. Flexible sigmoidoscopy revealed well
      demarcated, punched-out ulcers in the proximal rectum and distal sigmoid, with
      histology pathognomonic of cytomegalovirus (CMV). CMV DNA PCR was 51 140
      copies/mL. Despite prompt withdrawal of 6-MP, steroids and initiation of
      intravenous ganciclovir on day 2 of admission, his systemic illness, diarrhoea
      and fever persisted until day 19 of antiviral therapy. Other copathogens and
      lymphoma were ruled out on serology and CT scan, respectively. After an unusually
      prolonged course of antiviral therapy, the patient made a full clinical recovery,
      bloods normalised and there were two consecutive undetectable CMV DNA PCRs.

PMID- 29588844
TI  - Tacrolimus therapy in moderate to subacute ulcerative proctocolitis: a large
      single-centre cohort study.
AB  - Objective: To explore the 'real world' effectiveness of tacrolimus therapy for
      refractory ulcerative proctocolitis (UC). Design: Retrospective cohort study
      using prospectively collated clinical data. Setting: A single district general
      hospital in Kent, UK. Clinical decisions and regular monitoring were undertaken
      by a single expert in inflammatory bowel disease. Patients: All patients started
      on tacrolimus between January 2010 and August 2016 at Tunbridge Wells Hospital.
      Interventions: Following failure of conventional medication, tacrolimus was
      commenced at 0.5 mg/kg twice daily. Drug trough levels of 5-20 ng/mL were
      targeted. Other immunomodulation was stopped and steroids were weaned over 4-6
      weeks. Main outcome measures: Treatment duration was measured for each patient.
      If the drug was stopped, the rationale, including specific side effects, was
      recorded. The patient's subsequent management plan was noted. Results: Thirty
      five patients were started on tacrolimus (range: 18-85, median: 36 years).
      Disease extent included proctitis to pancolitis. Twenty-five patients derived no
      benefit. Four patients responded, but drug side effects necessitated withdrawal.
      Eighteen of these 29 patients (62%) underwent surgery. One patient, who had
      previously responded, stopped the drug after becoming pregnant (healthy
      subsequent birth). Therefore, 5 of 35 patients (14%) remain on tacrolimus with
      sustained clinical response, ranging from 6 to 76 (median: 32) months of
      treatment. Treatment was most effective for proctosigmoiditis. There were no
      other demographic or biological markers for success. Conclusions: In line with UK
      and European guidelines, tacrolimus can be beneficial for refractory UC. With
      appropriate monitoring, it appears treatment can be continued safely long term.

PMID- 29588845
TI  - Pedunculated polyp of the ileum protruding from a large diverticulum.
AB  - Introduction: A 52-year-old woman presented with iron deficiency anaemia and
      postprandial right lower quadrant pain. Abdominal examination was unremarkable
      and laboratory results showed mild anaemia (haemoglobin 11.3 g/dL). Upper and
      lower endoscopies did not reveal any source of bleeding. Video capsule endoscopy
      was performed which showed a large polypoid lesion in the mid-ileum (figure 1).
      Abdominal contrast enhanced CT demonstrated a heterogeneously enhancing
      pedunculated polyp measuring approximately 6 cm (figure 2). Retrograde double
      balloon enteroscopy was performed which revealed a large pedunculated polyp with
      hyperplastic-like mucosa protruding from a large diverticulum located
      approximately 70 cm proximal to the ileocaecal valve (figure 3A). The stalk
      appeared to arise from the base of the diverticulum (figure 3B). A technetium-99m
      pertechnetate scintigraphy revealed no ectopic gastric mucosa.Figure 1Video
      capsule endoscopy shows a large polypoid lesion.Figure 2CT shows a
      heterogeneously enhancing pedunculated polyp (arrow).Figure 3Retrograde double
      balloon enteroscopy images. (A) Large pedunculated polyp protruding from a large
      diverticulum. (B) The stalk appears to arise from the base of the diverticulum.
      Question: What is the diagnosis?

PMID- 29588846
TI  - Long-term follow-up of the use of maintenance antibiotic therapy for chronic
      antibiotic-dependent pouchitis.
AB  - Objective: Restorative proctolectomy is considered the procedure of choice in
      patients with ulcerative colitis who have failed medical therapy. Chronic
      pouchitis occurs in 10%-15% of patients, which often require long-term
      antibiotics to alleviate symptoms. Safety and efficacy of long-term maintenance
      antibiotics for chronic pouchitis has yet to be established. We aimed to assess
      the long-term safety and efficacy of maintenance antibiotic therapy for chronic
      pouchitis. Design: This was an observational study. We followed up patients who
      were diagnosed with chronic antibiotic-dependent pouchitis. Setting: Data were
      collected from our single specialist pouch centre. Patients: Patients with
      chronic antibiotic-dependent pouchitis who had been maintained on antibiotics
      continuously for at least 1 year with a least one follow-up visit. Main outcome
      measure: Development of pouch failure defined by the need for an ileostomy,
      patient-reported side effects of antibiotics and development of antibiotic
      resistance found on stool coliform testing. Results: Long-term use of antibiotics
      achieve remission in 21% of patients over a median follow-up of 102 (range 9
      125). Pouch failure in association with chronic pouchitis after a median follow
      up of 8.5 years occurred in 18%. Side effects of long-term antibiotic use
      occurred in 28% of patients, with resistance to antibiotics from at least one
      stool sample occurring in 78% patients. Conclusions: Although the use of
      antibiotics in chronic pouchitis may be justified, the use of long-term
      antibiotics must be weighed against potential complications associated with
      pouchitis and antibiotics.

PMID- 29588847
TI  - Impact and cost-effectiveness of formal gastroenterology outpatient referral
      Clinical Assessment Service.
AB  - Objective: The aim was to assess the financial and operational impact of our new
      gastroenterology referral pathway model on our services. Design: An electronic
      'Clinical Assessment Service' (CAS) proforma and an information platform were
      developed, and all data were analysed retrospectively. Setting: Royal
      Wolverhampton NHS Trust. Patients: 14 245 general practitioner (GP) referrals
      were received during January 2014-December 2016 with 9773 of them being triaged
      via our CAS. Main outcome measures: We looked into patients' clinical outcome
      along with departmental performance and finances. Results: A new outpatient
      appointment was offered to 60.1% (n=5873) of the CAS referred patients.
      Endoscopic or radiological investigations were requested for 29.2% (n=2854) of
      patients prior to deciding on further management plan. Out of those, 27% (n=765)
      went on to receive another gastroenterology (GI) clinic appointment. The
      remaining 21.3% (n=2089) of the CAS patients were discharged back to their GP
      following initial investigations. 5.5% (n=538) were discharged back to primary
      care with a letter of advice, whereas 5.2% (n=509) were deemed inappropriate for
      GI clinic and were redirected to other specialists. Overall, 32% (n=3127) of
      patients were managed without a face to face consultation in the GI clinic. This
      corresponds to 3136 less outpatient appointments with estimated reduced
      expenditure by the Clinical Commissioning Group (CCG) of L481K. The 18-week
      performance and waiting times remained stable despite the increasing referral
      population. The DNA rate dropped from 14% pre to 8.5%. Conclusions: Our clinical
      assessment model has, in addition to the clinical benefits, a considerable
      positive financial impact to the health economy.

PMID- 29588848
TI  - The 2018 Dr Falk Pharma UK/Core Awards are open for applications.

PMID- 29588849
TI  - Enhanced calcium ion mobilization in osteoblasts on amino group containing plasma
      polymer nanolayer.
AB  - Background: Biomaterial modifications-chemical and topographical-are of
      particular importance for the integration of materials in biosystems. Cells are
      known to sense these biomaterial characteristics, but it has remained unclear
      which physiological processes bio modifications trigger. Hence, the question
      arises of whether the dynamic of intracellular calcium ions is important for the
      characterization of the cell-material interaction. In our prior research we could
      demonstrate that a defined geometrical surface topography affects the cell
      physiology; this was finally detectable in a reduced intracellular calcium
      mobilization after the addition of adenosine triphosphate (ATP). Results: This
      new contribution examines the cell physiology of human osteoblasts concerning the
      relative cell viability and the calcium ion dynamic on different chemical
      modifications of silicon-titanium (Ti) substrates. Chemical modifications
      comprising the coating of Ti surfaces with a plasma polymerized allylamine
      (PPAAm)-layer or with a thin layer of collagen type-I were compared with a bare
      Ti substrate as well as tissue culture plastic. For this purpose, the human
      osteoblasts (MG-63 and primary osteoblasts) were seeded onto the surfaces for 24
      h. The relative cell viability was determined by colorimetric measurements of the
      cell metabolism and relativized to the density of cells quantified using crystal
      violet staining. The calcium ion dynamic of osteoblasts was evaluated by the
      calcium imaging analysis of fluo-3 stained vital cells using a confocal laser
      scanning microscope. The positively charged nano PPAAm-layer resulted in enhanced
      intracellular calcium ion mobilization after ATP-stimulus and cell viability.
      This study underlines the importance of the calcium signaling for the
      manifestation of the cell physiology. Conclusions: Our current work provides new
      insights into the intracellular calcium dynamic caused by diverse chemical
      surface compositions. The calcium ion dynamic appears to be a sensitive parameter
      for the cell physiology and, thus, may represent a useful approach for evaluating
      a new biomaterial. In this regard, reliable in vitro-tests of cell behavior at
      the interface to a material are crucial steps in securing the success of a new
      biomaterial in medicine.

PMID- 29588850
TI  - TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells
      through regulating miR-18a/PTEN axis.
AB  - Background: The acquisition of drug resistance has been considered as a main
      obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53
      induced lncRNA, plays a vital role in the progression of human cancers. However,
      little is known about the detailed function and molecular mechanism of TP53TG1 in
      cisplatin resistance of NSCLC. Methods: qRT-PCR analysis was used to detect the
      expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells. Western
      blot analysis was performed to determine the protein level of PTEN and cleaved
      caspase-3. Cell viability and IC50 value were measured by MTT assay. Cell
      apoptosis was confirmed by flow cytometry assay. Subcellular fractionation assay
      was used to identify the subcellular location of TP53TG1. Dual-luciferase
      reporter assay, RNA pull down assay and RNA immunoprecipitation assay were
      carried out to verify the interaction between TP53TG1 and miR-18a. Xenografts in
      nude mice were established to verify the effect of TP53TG1 on cisplatin
      sensitivity of NSCLC cells in vivo. Results: TP53TG1 level was downregulated in
      NSCLC tissues and cell lines. Upregulated TP53TG1 enhanced cisplatin sensitivity
      and apoptosis of A549/DDP cells, while TP53TG1 depletion inhibited cisplatin
      sensitivity and apoptosis of A549 cells. TP53TG1 suppressed miR-18a expression in
      A549 cells. Moreover, TP53TG1-mediated enhancement effect on cisplatin
      sensitivity was abated following the restoration of miR-18a expression in
      A549/DDP cells, while si-TP53TG1-induced decrease of cisplatin sensitivity and
      apoptosis was counteracted by miR-18a inhibitor in A549 cells. Furthermore,
      TP53TG1 promoted PTEN expression via inhibiting miR-18a. Finally, TP53TG1
      sensitized NSCLC cells to cisplatin in vivo. Conclusion: TP53TG1 increased the
      sensitivity of NSCLC cells to cisplatin by modulating miR-18a/PTEN axis,
      elucidating a novel approach to boost the effectiveness of chemotherapy for
      NSCLC.

PMID- 29588851
TI  - Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international
      dissemination of a new epidemic clone.
AB  - Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of
      hospital-acquired infections. New, presumably better-adapted strains of VRE
      appear unpredictably; it is uncertain how they spread despite improved infection
      control. We aimed to investigate the relatedness of a novel sequence type (ST) of
      vanB E. faecium - ST796 - very near its time of origin from hospitals in three
      Australian states and New Zealand. Methods: Following near-simultaneous outbreaks
      of ST796 in multiple institutions, we gathered then tested colonization and
      bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and
      phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data
      was explored to trace the spread of ST796. Results: A novel clone of vanB E.
      faecium (ST796) was first detected at one Australian hospital in late 2011, then
      in two New Zealand hospitals linked by inter-hospital transfers from separate
      Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New
      South Wales and was responsible for at least one major colonization outbreak in a
      Neonatal Intensive Care Unit without identifiable links between centers. No
      exceptional AMR was detected in the isolates. While WGS analysis showed very
      limited diversity at the core genome, consistent with recent emergence of the
      clone, clustering by institution was observed. Conclusions: Evolution of new E.
      faecium clones, followed by recognized or unrecognized movement of colonized
      individuals then rapid intra-institutional cross-transmission best explain the
      multi-center, multistate and international outbreak we observed.

PMID- 29588852
TI  - Treating refractory depression in Parkinson's disease: a meta-analysis of
      transcranial magnetic stimulation.
AB  - Background: Parkinson's disease (PD) is often accompanied by clinically
      identified depression. Providing effective pharmacotherapies that concomitantly
      treat both motor and psychological symptoms can pose a challenge to physicians.
      For this reason, alternatives to standard anti-depressant treatments, such as
      repetitive transcranial magnetic stimulation (rTMS), have been evaluated within
      the Parkinson's population. Methods: A literature search was conducted on the
      PubMed database for all studies that evaluated rTMS as a treatment in patients
      with both depression and PD. A meta-analysis was performed on all studies that
      reported mean pre- and post-rTMS depression inventory scores. Widely used
      depression inventories included both self-report and clinician-administered
      measures. Effect size for individual study groups and across all studies was
      calculated. Results: Six of 7 studies meeting inclusion criteria reported
      significantly improved depression scores, large effect sizes, and significant p
      values. Total weighted average effect size was calculated at 1.32 across all
      study groups that applied rTMS. Conclusions: Across all but one study, rTMS
      appears to effectively reduce depression scores among self-reported and clinician
      administered inventories. The total weight average effect size showed that, when
      considering study sample sizes and degree of findings, this form of
      neurostimulation can relieve PD patients of their depressive symptoms. Further,
      rTMS is a promising alternative to traditional anti-depressant therapies when
      treating refractory depression in patients with PD.

PMID- 29588853
TI  - Disordered eating in a Swedish community sample of adolescent girls: subgroups,
      stability, and associations with body esteem, deliberate self-harm and other
      difficulties.
AB  - Background: The developmental study of subtypes of disordered eating (DE) during
      adolescence may be relevant to understand the development of eating disorders.
      The purpose of the present study was to identify subgroups with different
      profiles of DE in a community sample of adolescent girls aged 13-15 years, and to
      study the stability of these profiles and subgroups over a one-year interval in
      order to find patterns that may need to be addressed in further research and
      prevention. Methods: Cluster analysis according to the LICUR procedure was
      performed on five aspects of DE, and the structural and individual stability of
      these clusters was analysed. The clusters were compared with regard to BMI, body
      esteem, deliberate self-harm, and other kinds of psychological difficulties.
      Results: The analysis revealed six clusters (Multiple eating problems including
      purging, Multiple eating problems without purging, Social eating problems, Weight
      concerns, Fear of not being able to stop eating, and No eating problems) all of
      which had structurally stable profiles and five of which showed stability at the
      individual level. The more pronounced DE clusters (Multiple eating problems
      including/without purging) were consistently associated with higher levels of
      psychological difficulties and lower levels of body esteem. Furthermore, girls
      that reported purging reported engaging in self-harm to a larger extent.
      Conclusions: Subgroups of 13-15 year old girls show stable patterns of disordered
      eating that are associated with higher rates of psychological impairment and
      lower body esteem. The subgroup of girls who engage in purging also engage in
      more deliberate self-harm.

PMID- 29588854
TI  - Experimental study of beam distortion due to fiducial markers during salvage HIFU
      in the prostate.
AB  - Background: Prostate cancer is frequently treated using external beam radiation
      therapy (EBRT). Prior to therapy, the prostate is commonly implanted with a small
      number of permanent fiducial markers used to monitor the position of the prostate
      during therapy. In the case of local cancer recurrence, high-intensity focused
      ultrasound (HIFU) provides a non-invasive salvage treatment option. However, the
      impact of the fiducial markers on HIFU treatment has not been thoroughly studied
      to date. The objective of this study was to experimentally investigate the effect
      of a single EBRT fiducial marker on the efficacy of HIFU treatment delivery using
      a tissue-mimicking material (TMM). Methods: A TMM with the acoustic properties of
      the prostate was developed based on a polyacrylamide hydrogel containing bovine
      serum albumin. Each phantom was implanted with a cylindrical fiducial marker and
      then sonicated using a 3.3 MHz focused bowl HIFU transducer. Two sets of
      experiments were performed. In the first, a single lesion was created at
      different positions along either the anteroposterior or left-right axes relative
      to the marker. In the second, a larger ablation volume was created by raster
      scanning. The size and position of the ablated volume were assessed using a
      millimetre grid overlaid on the phantom. Results: The impact of the marker on the
      position and size of the HIFU lesion was significant when the transducer focus
      was positioned within 7 mm anteriorly, 18 mm posteriorly or within 3 mm laterally
      of the marker. Beyond this, the generated lesion was not affected. When the focus
      was anterior to the marker, the lesion increased in size due to reflections. When
      the focus was posterior, the lesion decreased in size or was not present due to
      shadowing. Conclusions: The presence of an EBRT fiducial marker may result in an
      undertreated region beyond the marker due to reduced energy arriving at the
      focus, and an overtreated region in front of the marker due to reflections.
      Depending on the position of the targeted regions and the distribution of the
      markers, both effects may be undesirable and reduce treatment efficacy. Further
      work is necessary to investigate whether these results indicate the necessity to
      reconsider patient selection and treatment planning for prostate salvage HIFU
      after failed EBRT.

PMID- 29588855
TI  - Phage treatment of an aortic graft infected with Pseudomonas aeruginosa.
AB  - Management of prosthetic vascular graft infections caused by Pseudomonas
      aeruginosa can be a significant challenge to clinicians. These infections often
      do not resolve with antibiotic therapy alone due to antibiotic
      resistance/tolerance by bacteria, poor ability of antibiotics to permeate/reduce
      biofilms and/or other factors. Bacteriophage OMKO1 binding to efflux pump
      proteins in P. aeruginosa was consistent with an evolutionary trade-off: wildtype
      bacteria were killed by phage whereas evolution of phage-resistance led to
      increased antibiotic sensitivity. However, phage clinical-use has not been
      demonstrated. Here, we present a case report detailing therapeutic application of
      phage OMKO1 to treat a chronic P. aeruginosa infection of an aortic Dacron graft
      with associated aorto-cutaneous fistula. Following a single application of phage
      OMKO1 and ceftazidime, the infection appeared to resolve with no signs of
      recurrence.

PMID- 29588856
TI  - Diagnosis of GATA2 haplo-insufficiency in a young woman prompted by pancytopenia
      with deficiencies of B-cell and dendritic cell development.
AB  - Background: GATA2 deficiency presents with a spectrum of phenotypes including
      increased susceptibility to viral and bacterial infections, multi-lineage
      cytopenias, aplastic anemia, leukemic transformation and lymphedema. Allogeneic
      transplantation is only curative therapy for GATA2 deficiency, but is associated
      with significant treatment related morbidity and mortality. Given the spectrum of
      clinical presentation, accurate diagnosis of GATA2 deficiency is necessary to
      identify patients early in their disease course when allogeneic bone marrow
      transplantation may be of clinical benefit. Case presentation: In this report, we
      present a GATA2 mutation diagnosed in 23-year-old woman presenting with
      pancytopenia, recurring oral blisters, fatigue and chronic pain. We describe
      markedly low levels of mature B-cells in the blood and bone marrow and the
      absence of detectable blood dendritic cells with normal serum immunoglobulin
      levels and normal numbers of marrow plasma cells. She was ultimately diagnosed
      with GATA2 haplo-insufficiency due to a GATA2 germ-line mutation and underwent a
      successful allogeneic bone marrow transplant from a 10/10 HLA matched unrelated
      donor. Conclusions: The case illustrates the diagnostic difficulties in
      identifying GATA2 deficiencies and the importance of family history and genetic
      testing. GATA2 plays an important role in B-cell and dendritic cell development,
      and decreased numbers of those cells is a characteristic feature that should
      prompt consideration of GATA2 deficiency in a patient with pancytopenia.
      Maturation of B-cells to long-lived plasma cells is relatively unaffected in
      GATA2 deficiency. Allogeneic stem cell transplantation can correct immune
      deficiencies and prevent leukemic transformation in patients with GATA2
      deficiency.

PMID- 29588857
TI  - The role of maternal care in borderline personality disorder and dependent life
      stress.
AB  - Background: Borderline Personality Disorder (BPD) affects 0.9%-3.2% of
      adolescents, and more than 20% of inpatient adolescents. Life stress has been
      linked to BPD across the lifespan, and previous research in adults has linked BPD
      to dependent stress (i.e., stress induced by the individual). However, prior
      research has not examined dependent stress alongside BPD in adolescents.
      Additionally, the potential protective effect of maternal care has not been
      considered in this relation. This study tested a moderation model expecting that
      (1) BPD would be positively associated with dependent life stress, (2) maternal
      care would be negatively associated with BPD, and (3) maternal care would
      moderate the relation between BPD and dependent life stress. Method: The sample
      consisted of 184 adolescents recruited from an inpatient psychiatric facility
      serving a diverse population in the Southwestern United States. Dependent life
      stress, BPD, and maternal care were measured using the UCLA Life Stress
      Interview, DSM-IV Childhood Interview for BPD, and Kerns Security Scale,
      respectively. Results: Results supported the first two hypotheses; BPD diagnosis
      was significantly, positively associated with dependent life stress, and
      negatively associated with maternal availability and dependability. Contrary to
      the third hypothesis, no significant evidence that maternal care acts as a buffer
      in the relation between BPD and dependent life stress was found. Conclusions:
      Although maternal care was not found to moderate the association between BPD and
      dependent life stress, results supported previously found relations between BPD,
      dependent life stress, and maternal care, and did so within a diverse inpatient
      adolescent sample.

PMID- 29588858
TI  - Single nucleotide polymorphisms in asthma candidate genes TBXA2R, ADAM33 FCER1B
      and ORMDL3 in Pakistani asthmatics a case control study.
AB  - Background: Genetic variations in different loci and genes are important in
      asthma pathogenesis. There is much importance of various immunological pathways
      in the IgE secretion regulation. Alterations in any main part of these pathways
      can increase the risk of asthma development. Polymorphisms in these genetic
      markers can effect certain pathways which predict the asthma susceptibility. In
      the present study, SNPs directly or indirectly affecting the immunological
      process pathways are selected. Methods: This study was conducted to determine
      association of 16 SNPs in 10 candidate genes with asthma in Pakistani population
      in 333 asthmatic cases and 220 healthy controls. Genotyping was performed using
      the Sequenom Mass ARRAY iPLEX platform (14 SNPs) and TaqMan assay (2 SNPs).
      Results: The minor allele at two of the SNPs showed association with protection
      from asthma, rs1131882 in TBXA2R gene (OR 0.73, 95% CI 0.52-1.01, P = 0.05) and
      rs2280091 in the ADAM33 gene (OR 0.69, 95% CI 0.50-0.97, P = 0.03). For FCER1B
      gene, rs2583476 the asthmatic male gender had higher TT genotype counts as
      compared to controls (OR = 1.86, 95% CI = 1.09-3.17, p = 0.01). In rs11650680 of
      ORMDL3 gene the CT genotype is more prevalent in female asthma cases in
      comparison with female controls (OR = 1.99, 95% CI = 1.02-3.89, p = 0.03).
      Conclusions: This data suggests that variations at TBXA2R and ADAM33 genes are
      found to be associated with asthma susceptibility in Pakistan. FCER1B gene is
      associated with male and ORMDL3 in female asthmatics. These genetic markers can
      be important source of asthma risk in Pakistani population.

PMID- 29588859
TI  - Factors associated with the growing-finishing performances of swine herds: an
      exploratory study on serological and herd level indicators.
AB  - Background: Growing and finishing performances of pigs strongly influence farm
      efficiency and profitability. The performances of the pigs rely on the herd
      health status and also on several non-infectious factors. Many recommendations
      for the improvement of the technical performances of a herd are based on the
      results of studies assessing the effect of one or a limited number of infections
      or environmental factors. Few studies investigated jointly the influence of both
      type of factors on swine herd performances. This work aimed at identifying
      infectious and non-infectious factors associated with the growing and finishing
      performances of 41 French swine herds. Results: Two groups of herds were
      identified using a clustering analysis: a cluster of 24 herds with the highest
      technical performance values (mean average daily gain = 781.1 g/day +/- 26.3;
      mean feed conversion ratio = 2.5 kg/kg +/- 0.1; mean mortality rate = 4.1% +/-
      0.9; and mean carcass slaughter weight = 121.2 kg +/- 5.2) and a cluster of 17
      herds with the lowest performance values (mean average daily gain =715.8 g/day +/
      26.5; mean feed conversion ratio = 2.6 kg/kg +/- 0.1; mean mortality rate = 6.8%
      +/- 2.0; and mean carcass slaughter weight = 117.7 kg +/- 3.6). Multiple
      correspondence analysis was used to identify factors associated with the level of
      technical performance. Infection with the porcine reproductive and respiratory
      syndrome virus and the porcine circovirus type 2 were infectious factors
      associated with the cluster having the lowest performance values. This cluster
      also featured farrow-to-finish type herds, a short interval between successive
      batches of pigs (<=3 weeks) and mixing of pigs from different batches in the
      growing or/and finishing steps. Inconsistency between nursery and fattening
      building management was another factor associated with the low-performance
      cluster. The odds of a herd showing low growing-finishing performance was
      significantly increased when infected by PRRS virus in the growing-finishing
      steps (OR = 8.8, 95% confidence interval [95% CI]: 1.8-41.7) and belonging to a
      farrow-to-finish type herd (OR = 5.1, 95% CI = 1.1-23.8). Conclusions: Herd
      management and viral infections significantly influenced the performance levels
      of the swine herds included in this study.

PMID- 29588860
TI  - Technology-based functional assessment in early childhood intervention: a pilot
      study.
AB  - Background: Electronic patient-reported outcomes (e-PROs) may provide valid and
      feasible options for obtaining family input on their child's functioning for care
      planning and outcome monitoring, but they have not been adopted into early
      intervention (EI). The purpose of this pilot study was to evaluate the
      feasibility of implementing technology-based functional assessment into EI
      practice and to examine child, family, service, and environmental correlates of
      caregiver-reported child functioning in the home. Methods: In a cross-sectional
      design, eight individual EI providers participated in a 90-min technology-based
      functional assessment training to recruit participants and a 60-min semi
      structured focus group post data collection. Participants completed the Young
      Children's Participation and Environment Measure (YC-PEM) home section online and
      Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
      via iPad. Participants' EI service use data were obtained from administrative
      records. Results: A total of 37 caregivers of children between 6 and 35 months
      old (mean age = 19.4, SD = 7.7) enrolled, a rate of 44% (37/84) in 2.5 months.
      Providers suggested expanding staff training, gathering data during scheduled
      evaluations, and providing caregivers and providers with access to assessment
      summaries. Caregivers wanted their child's participation to change in 56% of home
      activities. Lower caregiver education and higher EI intensity were related to
      less child involvement in home activities. Conclusions: Implementing technology
      based functional assessment is feasible with modifications, and these data can be
      useful for highlighting child, family, and EI service correlates of caregiver
      reported child functioning that merit further study. Feasibility results informed
      protocol modifications related to EI provider training, timing of data
      collection, and management of EI service use data extraction, as preparation for
      a subsequent scale-up study that is underway.

PMID- 29588861
TI  - Standing Practice In Rehabilitation Early after Stroke (SPIRES): a functional
      standing frame programme (prolonged standing and repeated sit to stand) to
      improve function and quality of life and reduce neuromuscular impairment in
      people with severe sub-acute stroke-a protocol for a feasibility randomised
      controlled trial.
AB  - Background: The most common physical deficit caused by a stroke is muscle
      weakness which limits a person's mobility. Mobility encompasses activities
      necessary for daily functioning: getting in and out bed, on/off toilet, sitting,
      standing and walking. These activities are significantly affected in people with
      severe stroke who typically spend most of their time in bed or a chair and are
      immobile. Immobility is primarily caused by neurological damage but exacerbated
      by secondary changes in musculoskeletal and cardiorespiratory systems. These
      secondary changes can theoretically be prevented or minimised by early
      mobilisation, in this case standing up early post-stroke.Standing up early post
      stroke has been identified as an important priority for people who have suffered
      a severe stroke. However, trials of prolonged passive standing have not
      demonstrated any functional improvements. Conversely, task-specific training such
      as repeated sit-to-stand has demonstrated positive functional benefits. This
      feasibility trial combines prolonged standing and task-specific strength training
      with the aim of determining whether this novel combination of physiotherapy
      interventions is feasible for people with severe stroke as well as the overall
      feasibility of delivering the trial. Methods/design: This is a pragmatic multi
      centre parallel single-blinded two-armed feasibility randomised controlled trial.
      Fifty people with a diagnosis of severe stroke will be randomly allocated to
      either the functional standing frame programme or usual physiotherapy. All
      patient participants will be assessed at baseline and followed up at 3 weeks,
      then 3, 6 and 12 months post-randomisation. Trial objectives are to determine the
      feasibility according to the following indicators:: (i) Process: recruitment and
      retention rate, ability to consent, eligibility criteria, willingness/ability of
      physiotherapists to recruit, willingness of patients to be randomised, and
      acceptability of the intervention; (ii) Resource: burden and potential costs;
      (iii) Management: treatment fidelity, participant adherence, acceptability and
      completeness of outcome measures, impact and management or orthostatic
      hypotension; and (iv) Safety: number and nature of adverse and serious adverse
      events. Discussion: The functional standing frame programme addresses a key
      concern for people who have suffered a severe stroke. However, several
      uncertainties exist which need to be understood prior to progressing to a full
      scale trial, including acceptability and tolerance of the functional standing
      frame programme intervention and practicality of the trial procedures. This
      feasibility trial will provide important insights to resolve these uncertainties.
      Trial registration: International Standard Randomised Controlled Trial Number
      ISRCTN15412695. Registration on 19 December 2016.

PMID- 29588862
TI  - Invasive urodynamic testing prior to surgical treatment for stress urinary
      incontinence in women: cost-effectiveness and value of information analyses in
      the context of a mixed methods feasibility study.
AB  - Background: INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of
      Incontinence Gives Added Therapeutic Effect?) was a mixed methods study to assess
      the feasibility of a future randomised controlled trial of invasive urodynamic
      testing (IUT) prior to surgery for stress urinary incontinence (SUI) in women.
      Here we report one of the study's five components, with the specific objectives
      of (i) exploring the cost-effectiveness of IUT compared with clinical assessment
      plus non-invasive tests (henceforth described as 'IUT' and 'no IUT' respectively)
      in women with SUI or stress-predominant mixed urinary incontinence (MUI) prior to
      surgery, and (ii) determining the expected net gain (ENG) from additional
      research. Methods: Study participants were women with SUI or stress-predominant
      MUI who had failed to respond to conservative treatments recruited from seven UK
      urogynaecology and female urology units. They were randomised to receive either
      'IUT' or 'no IUT' before undergoing further treatment. Data from 218 women were
      used in the economic analysis. Cost utility, net benefit and value of information
      (VoI) analyses were performed within a randomised controlled pilot trial. Costs
      and quality-adjusted life years (QALYs) were estimated over 6 months to determine
      the incremental cost per QALY of 'IUT' compared to 'no IUT'. Net monetary benefit
      informed the VoI analysis. The VoI estimated the ENG and optimal sample size for
      a future definitive trial. Results: At 6 months, the mean difference in total
      average cost was L138 (p = 0.071) in favour of 'IUT'; there was no difference in
      QALYs estimated from the SF-12 (difference 0.004; p = 0.425) and EQ-5D-3L
      (difference - 0.004; p = 0.725); therefore, the probability of IUT being cost
      effective remains uncertain. The estimated ENG was positive for further research
      to address this uncertainty with an optimal sample size of 404 women.
      Conclusions: This is the largest economic evaluation of IUT. On average, up to 6
      months after treatment, 'IUT' may be cost-saving compared to 'no IUT' because of
      the reduction in surgery following invasive investigation. However, uncertainty
      remains over the probability of 'IUT' being considered cost-effective, especially
      in the longer term. The VoI analysis indicated that further research would be of
      value. Trial registration: ISRCTN. ISRCTN71327395. Registered 7 June 2010.

PMID- 29588863
TI  - Epidemiology of antibiotic-resistant wound infections from six countries in
      Africa.
AB  - Introduction: Little is known about the antimicrobial susceptibility of common
      bacteria responsible for wound infections from many countries in sub-Saharan
      Africa. Methods: We performed a retrospective review of microbial isolates
      collected based on clinical suspicion of wound infection between 2004 and 2016
      from Mercy Ships, a non-governmental organisation operating a single mobile
      surgical unit in Benin, Congo, Liberia, Madagascar, Sierra Leone and Togo.
      Antimicrobial resistant organisms of interest were defined as methicillin
      resistant Staphylococcus aureus (MRSA) or Enterobacteriaceae resistant to third
      generation cephalosporins. Generalised mixed-effects models accounting for
      repeated isolates in a patient, potential clustering by case mix for each field
      service, age, gender and country were used to test the hypothesis that rates of
      antimicrobial resistance differed between countries. Results: 3145 isolates from
      repeated field services in six countries were reviewed. In univariate analyses,
      the highest proportion of MRSA was found in Benin (34.6%) and Congo (31.9%),
      while the lowest proportion was found in Togo (14.3%) and Madagascar (14.5%);
      country remained a significant predictor in multivariate analyses (P=0.002). In
      univariate analyses, the highest proportion of third-generation cephalosporin
      resistant Enterobacteriaceae was found in Benin (35.8%) and lowest in Togo
      (14.3%) and Madagascar (16.3%). Country remained a significant predictor for
      antimicrobial-resistant isolates in multivariate analyses (P=0.009). Conclusion:
      A significant proportion of isolates from wound cultures were resistant to first
      line antimicrobials in each country. Though antimicrobial resistance isolates
      were not verified in a reference laboratory and these data may not be
      representative of all regions of the countries studied, differences in the
      proportion of antimicrobial-resistant isolates and resistance profiles between
      countries suggest site-specific surveillance should be a priority and local
      antimicrobial resistance profiles should be used to guide empiric antibiotic
      selection.

PMID- 29588864
TI  - The Passage of CARA: Implications for Patients With Cancer Pain.

PMID- 29588865
TI  - Superhuman Strength in Cancer.

PMID- 29588866
TI  - Idelalisib: Practical Tools for Identifying and Managing Adverse Events in
      Clinical Practice.
AB  - Idelalisib is a first-in-class oral selective inhibitor of phosphatidylinositol 3
      kinase delta, which is selectively expressed in hematopoietic cells, where it is
      critical to B-cell receptor signaling and B-cell development and function.
      Idelalisib is approved in the United States for the treatment of relapsed chronic
      lymphocytic leukemia (CLL; in combination with rituximab), relapsed follicular
      lymphoma (FL), and small lymphocytic lymphoma (SLL) and in the European Union for
      the treatment of CLL (in combination with rituximab). Approval was based on
      clinical activity in a phase II trial in indolent non-Hodgkin lymphoma and a
      phase III trial in CLL. Because idelalisib is a relatively new treatment option
      for patients with relapsed CLL, SLL, and FL, with a safety profile distinct from
      other agents, it is important for advanced practitioners (APs) to familiarize
      themselves with the adverse event (AE) profile and educate their patients as
      well. As active members of the oncology care team, APs can play a vital role in
      optimizing outcomes in patients receiving idelalisib therapy. This review will
      familiarize APs with the AE profile of idelalisib and provide practical
      information about the identification and management of AEs associated with
      idelalisib therapy.

PMID- 29588867
TI  - Clinical Management of Bowel Dysfunction After Low Anterior Resection for Rectal
      Cancer.
AB  - The American Cancer Society estimated that 39,610 new cases of rectal cancer were
      diagnosed in the United States in 2015. Surgery is the primary treatment for
      rectal cancer, with the majority of patients undergoing sphincter-preserving
      surgery with low anterior resection. Although low anterior resection can prevent
      patients from having a permanent colostomy, bowel dysfunction may occur in 60% to
      90% of patients. Bowel dysfunction symptoms may include fecal and gas
      incontinence, urgency, frequent bowel movements, clustering of stools, and
      difficulty emptying. The symptoms collectively are referred to as low anterior
      resection syndrome (LARS) and adversely affect quality of life. There are no
      specific therapies for management of LARS. This comprehensive literature review
      evaluates evidence-based, clinical nonsurgical interventions for symptom
      management of LARS and will assist advanced practitioners in recognizing symptoms
      and implementing clinical interventions in the outpatient setting for management
      of LARS.

PMID- 29588868
TI  - Case Study of a Young Adult With Ewing Sarcoma.

PMID- 29588870
TI  - Appraising Travelbee's Human-to-Human Relationship Model.

PMID- 29588869
TI  - A Descriptive, Longitudinal Study of Quality of Life and Perceived Health Needs
      in Patients With Head and Neck Cancer.
AB  - Patients with head and neck cancer have numerous concerns and symptoms in the
      first year of posttreatment survivorship and are especially vulnerable at the end
      of treatment and 1 month posttreatment. This article shares the findings of a
      descriptive, longitudinal study of health-related quality of life (HRQOL) in
      patients with head and neck cancer from the beginning of treatment through 12
      months posttreatment. The primary objective of this study was to describe the
      symptom experience and health needs of patients receiving radiation for head and
      neck cancer to support the establishment of an advanced practitioner (AP) clinic
      for head and neck cancer survivors. Significant findings in this study showed
      HRQOL at the end of treatment was significantly lower than baseline (p < .001).
      Low scores persisted through 1 month, with gradual recovery by 12 months. Fatigue
      and anxiety had the highest mean scores, yet anxiety improved with time, whereas
      fatigue did not. Positive human papillomavirus status was statistically
      associated with higher anxiety. Socioeconomic status negatively impacted HRQOL.
      Themes of perceived health needs were managing oral symptoms, returning to a
      normal life, and regaining energy. The AP in oncology can play a pivotal role in
      providing comprehensive assessment, symptom management, health education, and
      supportive counseling in this population throughout treatment and survivorship.

PMID- 29588871
TI  - Understanding Biomarkers in Early-Stage Invasive Breast Cancer: Tools From the
      ASCO Clinical Guideline.

PMID- 29588873
TI  - Community's Emergency Preparedness for Flood Hazards in Dire-dawa Town, Ethiopia:
      A Qualitative Study.
AB  - Background: Emergency preparedness at all levels (individuals and communities) is
      the corner stone of effective response to the increasing trends of global
      disasters due to man-made and natural hazards. It is determined by different
      factors, including (among others) past direct and indirect exposures to hazards.
      This study was carried out in Dire Dawa town, Ethiopia, which in the past
      experienced frequent flooding events, yet dearth of information exists about
      preparedness in the area.  The aim of the study was to assess the levels of
      emergency preparedness for flood hazards at households and communities levels.
      Methods: The study was conducted in a qualitative approach and was conducted in
      Dire Dawa town, which has been divided into nine administrative-units called
      Kebeles. Two focus group discussions were held in two of these units (Kebele-05
      and 06), each focus group comprising twelve people (all above 18 years of age),
      and in total 24 people (13 females and 11 males) took part in the study. Open
      ended questions were used that could guide the discussions, and the discussions
      were audio-taped and transcribed. The results were translated from local language
      to English and qualitatively presented. Results: The findings of focus group
      discussions showed that the local government in collaboration with the federal
      government built the flood protection dams in areas where flood hazards have been
      thought to be repeatedly wreaking havoc, specifically after the flood disaster of
      the year 2006. In addition, in Kebele-05, where one Non-Governmental Organization
      (NGO) was operating on flood hazards prevention and mitigation program, some non
      structural emergency preparedness measures were undertaken by the communities.
      These non-structural measures (the major ones) entailed: establishment of
      committees recruited from residents and training them to raise awareness among
      communities on emergency preparedness; some residents made changes to their own
      houses (retrofitted) and put sandbags around their houses to temporarily protect
      the flooding; establishment of communication channels between communities to
      alarm each other in the event of flood disaster; and reforestation of the already
      deforested mountainous areas surrounding the town. However, concerns were raised
      by study participants about strengths of the constructed flood protection dams.
      Furthermore, the non-structural emergency preparedness measures identified by
      this study were not comprehensive; for example, residents were not trained in
      first aid, first aid kits were not provided, there was no linkage being
      established between communities and health facilities so as to provide emergency
      medical care to victims in the event of flood disaster. Discussion: The findings
      of this study concur with some of the previous quantitative studies' results in
      that the past direct and indirect disaster experiences invoke preparedness
      intention and actual preparedness for flood hazards at individuals, communities
      and organizations levels. The only one quantitative and behavioral based study
      conducted thus far in Dire Dawa town reported the strong association of past
      flood disaster experience with household emergency preparedness. Among the
      residents there was a tendency to rely on the dams to be constructed with "good
      quality" and "higher strength" than making preparedness efforts on their own at
      their households. Structural measures such as building of dams, dikes, levees,
      and channel improvements could be means of mitigation measures; however, solely
      relying on these measures could have far reaching consequences. Conclusions: To
      mitigate flood hazards, dams were built and in addition, in Kebele-05 where an
      NGO was operating, some non-structural emergency preparedness measures were
      undertaken. In the course of construction of flood protection dams, ensuring
      communities' involvement is needed; and at the same time undertaking
      comprehensive non-structural emergency preparedness measures in all Kebeles is
      highly recommended. Key words: Emergency, Preparedness, Flood, Dire Dawa,
      Ethiopia.

PMID- 29588872
TI  - Preventing Peanut Allergy.
AB  - The rising prevalence of food allergy and specifically peanut allergy has had
      significant implications for affected patients, families, and society. The
      current standard of care remains strict avoidance and the use of emergency
      medications for accidental ingestions. There is recent evidence-based information
      to suggest that one approach to preventing peanut allergy lies in early
      introduction of peanut. This represents a paradigm shift from previous
      recommendations and has led to updated guidelines in the United States, Europe,
      and Australasia on the introduction of potentially allergenic foods in the infant
      diet. This new approach to prevention has some practical obstacles and challenges
      associated with its implementation. There is also growing interest in the role of
      maintaining a healthy skin barrier in prevention of sensitization and food
      allergy. Other approaches, including pro- and prebiotics, prenatal maternal
      dietary avoidance, breastfeeding, and the use of specific formulas, have not
      shown reproducibly favorable results. As children with peanut allergy are
      unlikely to outgrow their food allergy, early oral immunotherapy in those with
      established peanut allergy is being investigated with the hopes of altering the
      natural history of an otherwise lifelong disease.

PMID- 29588874
TI  - Clinical and Laboratory Profile of Zika and Dengue Infected Patients: Lessons
      Learned From the Co-circulation of Dengue, Zika and Chikungunya in Brazil.
AB  - BACKGROUND: The current triple epidemic caused by dengue, zika and chikungunya
      constitutes a serious health problem in Brazil. The aim of this study was to
      investigate acute samples (up to the 7 days of symptoms) from patients presenting
      acute fever syndrome suspected as arboviral infection and characterize the
      clinical and laboratorial profile during the co-circulation of dengue, zika and
      chikungunya in Campo Grande, Mato Grosso do Sul (MS), midwest region of Brazil.
      METHODS: All suspected cases (n=134) were tested by using serological and
      molecular diagnostic tests including DENV, ZIKV and CHIKV RT-PCR, Dengue
      nonstructural protein 1 (NS1) antigen capture ELISA, anti- DENV IgM ELISA and
      anti-CHIKV IgM ELISA. In addition, clinical, hematological and biochemical
      parameters of infected patients were analyzed. RESULTS:  It was observed that
      79.1% of the blood samples were confirmed for ZIKV and/or DENV infection Of
      those, 38.0% patients were DENV monoinfected, 26.8% were ZIKV monoinfected and
      13.4% were DENV/ZIKV co-infected. Seven patients presented Chikungunya IgM
      antibodies indicating a previous CHIKV infection. Common symptoms included fever,
      rash, arthralgia, myalgia, prostration, headache and conjunctivitis. Statistical
      analysis showed that pruritus and edema were associated with ZIKV infection while
      prostration and vomiting were more associated with dengue. Additionally, total
      protein and ALT levels were significantly different in DENV patients compared to
      ZIKV ones. Some DENV infected patients as well as co-infected needed
      hospitalization and venous hydration. Otherwise, most ZIKV infected patients
      presented mild clinical course. Among the pregnant women studied (n=11), three
      were ZIKV monoinfected while four were DENV monoinfected and two were DENV-1/ZIKV
      coinfected. In general, normal birth outcomes were observed except for the death
      due to respiratory insufficiency of one baby born to a mother coinfected with
      DENV-1/ZIKV. CONCLUSIONS:  Herein, we provide evidence of the co-circulation of
      DENV, ZIKV and CHIKV infections in the Campo Grande, MS, Brazil, with a high
      frequency of DENV-1/ZIKV coinfection. Laboratorial diagnosis poses a challenge
      where those arboviruses are endemic and differential diagnosis proved to
      imperative for cases characterization. The knowledge about disease severity
      during arbovirus coinfections is still scarce and there are several issues
      emphasizing the importance of adequate management of patients at risk areas.

PMID- 29588875
TI  - Incidence Prediction for the 2017-2018 Influenza Season in the United States with
      an Evolution-informed Model.
AB  - Introduction: Seasonal influenza is responsible for a high disease burden in the
      United States and worldwide. Predicting outbreak size in advance can contribute
      to the timely control of seasonal influenza by informing health care and
      vaccination planning. Methods: Recently, a process-based model was developed for
      forecasting incidence dynamics ahead of the season, with the approach validated
      by several statistical criteria, including an accurate real-time prediction for
      the past 2016-2017 influenza season before it started. Results: Based on this
      model and data up to June 2017, a forecast for the upcoming 2017-2018 influenza
      season is presented here, indicating an above-average, moderately severe,
      outbreak dominated by the H3N2 subtype. Discussion: The prediction is consistent
      with surveillance data so far, which already indicate the predominance of H3N2.
      The forecast for the upcoming 2017-2018 influenza season reinforces the
      importance of the on-going vaccination campaign.

PMID- 29588876
TI  - Ectopic Telomerase Expression Fails to Maintain Chondrogenic Capacity in Three
      Dimensional Cultures of Clinically Relevant Cell Types.
AB  - The poor healing capacity of cartilage and lack of effective treatment for
      associated disease and trauma makes it a strong candidate for a regenerative
      medicine approach. Potential therapies tested to date, although effective, have
      met with a number of intrinsic difficulties possibly related to limited
      autologous chondrocyte cell yield and quality of cartilage produced. A potential
      mechanism to bypass limited cell yields and improve quality of differentiation is
      to immortalize relevant cell types through the ectopic expression of telomerase.
      Pellet cultures of human chondrocytes (OK3), bone marrow mesenchymal stem cells
      (BMA13), and embryonic stem cell (H1 line)-derived cells (1C6) and their human
      telomerase reverse transcriptase (hTERT) transduced counterparts were maintained
      for 20 days in standard maintenance medium (MM) or transforming growth factor
      beta3-supplemented prochondrogenic medium (PChM). Pellets were assessed for
      volume and density by microcomputed tomography. Quantitative gene expression
      (COL1A2, COL2A1, COL3A1, COL6A3, COL10A1, ACAN, COMP, SOX9); sulfated
      glycosaminoglycans (sGAGs), and DNA quantification were performed. Histology and
      immunohistochemistry were used to determine matrix constituent distribution.
      Pellet culture in PChM resulted in significantly larger pellets with an overall
      increased density when compared with MM culture. Gene expression analysis
      revealed similarities in expression patterns between telomerase-transduced and
      parental cells in both MM and PChM. Of the three parental cell types examined OK3
      and BMA13 produced similar amounts of pellet-associated sGAG in PChM (4.62 +/-
      1.20 and 4.91 +/- 1.37 MUg, respectively) with lower amounts in 1C6 (2.89 +/-
      0.52 MUg), corresponding to 3.1, 2.3, and 1.6-fold increases from day 0. In
      comparison, telomerase-transduced cells all had much lower sGAG with OK3H at 2.74
      +/- 0.11 MUg, BMA13H 1.29 +/- 0.34 MUg, and 1C6H 0.52 +/- 0.01 MUg corresponding
      to 1.2, 0.87, and 0.34-fold changes compared with day 0. Histology of day 20
      pellets displayed reduced staining overall for collagens and sGAG in telomerase
      transduced cells, most notably with alterations in aggrecan and collagen VI; all
      cells stained positively for collagen II. We conclude that while telomerase
      transduction may be an effective technique to extend cellular proliferative
      capacity, it is not sufficient in isolation to sustain a naive chondrogenic
      phenotype across multiple cell types.

PMID- 29588878
TI  - Withdrawal of: Shifts in the Enjoyment of Healthy and Unhealthy Behaviors Affect
      Short- and Long-Term Postbariatric Weight Loss by Vuorinen A-L, Strahilevitz MA,
      Wansink B, and Safer DL. Bariatr Surg Pract Patient Care 2017;12(1):35-42. DOI:
      10.1089/bari.2016.0036.

PMID- 29588877
TI  - Patient-Perceived Autonomy and Long-Acting Reversible Contraceptive Use: A
      Qualitative Assessment in a Midwestern, University Community.
AB  - Long-acting reversible contraceptives (LARCs) are the most effective
      contraceptives and are first-line recommendations for most women. However, young
      women use these methods at relatively low rates. Given concern with contraceptive
      coercion, an underexamined factor contributing to LARC attitudes is women's
      perceived reproductive and bodily autonomy in regard to LARC. We conducted focus
      group discussions and interviews regarding LARC perceptions and knowledge with 50
      women between the ages of 18 and 29. We used a modified grounded theory approach
      to analyze young women's impressions of autonomy in relation to contraceptives
      more generally and LARC more specifically, both among ever-users and never-users.
      Four themes emerged regarding women's perceived autonomy with LARC. Control over
      pregnancy, active participation versus external agent, control over bleeding
      patterns, and autonomy in the provider/patient relationship. Within most themes,
      women made both positive and negative associations between perceived autonomy and
      LARC. The provider/patient relationship was a modifier of other themes, in that
      cooperative relationships may overshadow other perceived reductions in autonomy,
      and more unbalanced relationships may heighten perceived reductions in autonomy.
      Ever-users were more likely to report increased autonomy with LARC use, whereas
      never-users were more likely to express concerns about loss of autonomy with
      LARC. This study suggests that perceived autonomy may influence women's
      perceptions of LARC as well as their uptake of these contraceptive methods, with
      several factors both positively and negatively related to women's perceived
      autonomy. We encourage the integration of these findings into patient-centered
      counseling as well as educational materials for LARC.

PMID- 29588879
TI  - Suprasellar Tumors (Part 2).

PMID- 29588880
TI  - Endoscopic Endonasal Approach to a Suprasellar Craniopharyngioma.
AB  - We present the case of a 57-year-old male who presented with progressive right
      side vision loss whose workup revealed a large suprasellar lesion with invasion
      of the third ventricle. The pituitary stalk was not visible. Hormonal panel
      showed no hormonal deficits. The initial diagnosis was of a type II
      transinfundibular craniopharyngioma (as classified by Kassam et al). An
      endoscopic endonasal transplanum transtuberculum approach was done using a
      standard binostril four-hand technique, with the patient positioned supine with
      the head turned to the right side and tilted to the left, fixed in a three-pin
      head clamp, under imaging guidance. The tumor was carefully dissected away from
      the optic apparatus while preserving the vessels, mainly the superior hypophyseal
      artery. The stalk was identified around the tumor and preserved. The third
      ventricle was entered and inspected at the end of the procedure and a near-total
      resection (a small residual in the right hypothalamus) with decompression of the
      optic apparatus was achieved. Reconstruction was done in a multilayered fashion,
      using collagen matrix and a nasoseptal flap. Patient had an uneventful
      postoperative stay and was discharged on POD 4, neurologically stable with no
      hormonal deficits. Pathology confirmed an adamantinomatous craniopharyngioma. Due
      to a small growth of the residual, patient underwent fractionated stereotactic
      radiation (50.4Gy in 28 sessions). He presented with panhypopituitarism 2 years
      after radiation therapy. At 3-month follow-up, his vision was back to normal and
      6-year postoperative magnetic resonance imaging showed no signs of recurrence.
      The link to the video can be found at: https://youtu.be/chG7XIz7a_A .

PMID- 29588881
TI  - Orbitopterional Approach for the Resection of a Suprasellar Craniopharyngioma:
      Adapting the Strategy to the Microsurgical and Pathologic Anatomy.
AB  - Objectives  To describe the orbitopterional approach for the resection of a
      suprasellar craniopharyngioma with emphasis on the microsurgical and pathological
      anatomy of such lesions. Design  After completing the orbitopterional craniotomy
      in one piece including a supraorbital ridge osteotomy, the Sylvian fissure was
      split in a distal to proximal direction. The ipsilateral optic nerve and internal
      carotid artery were identified. Establishing a corridor to the tumor through both
      the opticocarotid and optic cisterns allowed for a wide angle of attack. Using
      both corridors, a microsurgical gross total resection was achieved. A radical
      resection required transection of the stalk at the level of the hypothalamus.
      Photographs of the region are borrowed from Dr Rhoton's laboratory to illustrate
      the microsurgical anatomy. Understanding the cisternal and topographic
      relationships of the optic nerve, optic chiasm, and internal carotid artery is
      critical to achieving gross total resection while preserving normal anatomy.
      Participants  The surgery was performed by the senior author assisted by Dr.
      Jaafar Basma. The video was edited by Dr. Vincent Nguyen. Outcome Measures 
      Outcome was assessed with extent of resection and postoperative visual function.
      Results  A gross total resection of the tumor was achieved. The patient had
      resolution of her bitemporal hemianopsia. She had diabetes insipidus with normal
      anterior pituitary function. Conclusions  Understanding the microsurgical anatomy
      of the suprasellar region and the pathological anatomy of craniopharyngiomas is
      necessary to achieve a good resection of these tumors. The orbitopterional
      approach provides the appropriate access for such endeavor. The link to the video
      can be found at: https://youtu.be/Be6dtYIGqfs .

PMID- 29588882
TI  - Endoscopic Endonasal Approach for a Suprasellar Craniopharyngioma.
AB  - Objectives  The current video presents the nuances of an endoscopic endonasal
      approach to a suprasellar craniopharyngioma. Design  The video analyzes the
      presentation, preoperative workup and imaging, surgical steps and technical
      nuances of the surgery, the clinical outcome, and follow-up imaging. Setting  The
      patient was treated by a skull base team consisting of a neurosurgeon and an ENT
      surgeon, at a teaching academic institution. Participants  The case refers to a
      67-year-old man who presented with vision loss and headaches, and was found to
      have a suprasellar mass, with imaging characteristics consistent with a
      craniopharyngioma. Main Outcome Measures  The main outcome measures consistent of
      the reversal of the patient symptoms (vision loss and headaches), the recurrence
      free survival based on imaging, as well as the absence of any complications.
      Results  The patient's vision improved after the surgery; at his last follow-up
      there was no evidence of recurrence on imaging. Conclusions  The endoscopic
      endonasal approach is safe and effective in treating suprasellar
      craniopharyngiomas. The link to the video can be found at:
      https://youtu.be/p1VXbwnAWCo .

PMID- 29588883
TI  - Resection of a Retrochiasmatic Craniopharyngioma by Combined Modified Orbital
      Craniotomy and Transnasal Endoscopic Techniques.
AB  - A 20-year-old patient presented with hydrocephalus but intact vision and hormone
      function. The MRI showed a large seller, suprasellar and third ventricular mass.
      We chose a combined approach utilizing the translyvian, lamina terminals route,
      with a possible interhemispheric approach. But, we also utilized a transnasal
      endoscopic approach for the tumor that remained below the diaphragma sellae. The
      patient did well, with complete tumor resection via a staged approach, but did
      require hormone replacement. The link to the video can be found at:
      https://youtu.be/yzpfOxzI4cQ .

PMID- 29588884
TI  - Endoscopic Endonasal Approach for Resection of a Pediatric Craniopharyngioma:
      Operative Video and Technical Nuances.
AB  - We present a pediatric case of a retrochiasmatic craniopharyngioma in the
      suprasellar region with third ventricular extension that was resected through a
      purely endoscopic endonasal approach (EEA) via the transplanum transtuberculum
      corridor. The patient is a 12-year-old boy who presented with progressive visual
      loss and panhypopituitarism. The EEA allows direct visualization of the
      undersurface of the optic chiasm and hypothalamus so that safe and meticulous
      tumor dissection can be performed to preserve these critical neurovascular
      structures. This video atlas demonstrates the operative technique and surgical
      nuances of the endoscopic skull base approach, microdissection of the tumor from
      the critical neurovascular structures, and multilayered reconstruction of the
      skull base defect with a nasoseptal flap. A gross total resection was achieved,
      and the patient was neurologically intact with improved visual acuity and visual
      fields. In summary, the EEA via the transplanum transtuberculum corridor is an
      important strategy in the armamentarium for surgical management of pediatric
      craniopharyngiomas. The link to the video can be found at:
      https://youtu.be/bmgO_PMRHPk .

PMID- 29588885
TI  - Microsurgical Resection of Suprasellar Craniopharyngioma-Technical Purview.
AB  - Objectives  Complete surgical resection is an important prognostic factor for
      recurrence and is the best management for craniopharyngioma. This operative video
      demonstrates the technical nuances in achieving complete resection of a
      suprasellar craniopharyngioma. Design and Setting  The surgery was performed in a
      middle-aged lady who presented with the history of progressive bitemporal
      hemianopia and excessive sleepiness over 8 months. On imaging, suprasellar
      craniopharyngioma was identified. The tumor was approached through opticocarotid
      cistern and lamina terminalis. Exposure of bilateral optic nerves, right internal
      carotid artery, anterior cerebral artery, and its perforator branches was then
      afforded and the tumor was gross totally resected. Results  The author
      demonstrates step-by-step technique of microsurgical resection of suprasellar
      craniopharyngioma. The narrow corridor to deeper structures, intricacies of
      multiple perforator vessels, and the technique of arachnoid and capsule
      dissection are the main challenging factors for the gross total resection of
      craniopharyngioma. The tumor portion which lies under the ipsilateral optic nerve
      is a blind spot region with a high chance of leaving residual tumor. Mobilization
      of optic nerve may endanger visual function too. The use of handheld mirror
      ['mirror-technique'] helps in better visualization of this blind spot and achieve
      complete excision. Conclusions  The technical pearls of craniopharyngioma surgery
      include the optimum utilization of translamina terminalis route, wide opening of
      the cisterns, meticulous separation of deep perforator vessels, capsular
      mobilization/traction avoidance, and the use of "mirror-technique" for blind-spot
      visualization. These surgical strategies help to achieve complete resection
      without causing neurological deficit. The link to the video can be found at:
      https://youtu.be/9wHJ4AUpG50 .

PMID- 29588886
TI  - Endoscopic Endonasal Transplanum Transtuberculum Approach for the Resection of a
      Large Suprasellar Craniopharyngioma.
AB  - Objectives  To demonstrate an endoscopic endonasal transplanum transtuberculum
      approach for the resection of a large suprasellar craniopharyngioma. Design 
      Single-case-based operative video. Setting  Tertiary center with dedicated skull
      base team. Participants  A 72-year-old male patient diagnosed with a suprasellar
      craniopharyngioma. Main Outcomes Measured  Surgical resection of the tumor and
      preservation of the normal surrounding neurovascular structures. Results  A 72
      year-old male patient presented with a 1-year history of progressive bitemporal
      visual loss. He also referred symptoms suggestive of hypogonadism. Neurological
      examination was unremarkable and endocrine workup demonstrated mildly elevated
      prolactin levels. Magnetic resonance images demonstrated a large solid-cystic
      suprasellar lesion, consistent with the diagnosis of craniopharyngioma. The
      lesion was retrochiasmatic, compressed the optic chiasm, and extended into the
      interpeduncular cistern ( Fig. 1 ). Because of that, the patient underwent an
      endoscopic endonasal transplanum transtuberculum approach. 1 2 3 The nasal stage
      consisted of a transnasal transseptal approach, with complete preservation of the
      patient's left nasal cavity. 4 The cystic component of the tumor was decompressed
      and its solid part was resected. It was possible to preserve the surrounding
      normal neurovascular structures ( Fig. 2 ). Skull base reconstruction was
      performed with a dural substitute, a fascia lata graft, and a right nasoseptal
      flap ( Video 1 ). The patient did well after surgery and referred complete visual
      improvement. However, he also presented pan-hypopituitarism on long-term follow
      up. Conclusions  The endoscopic endonasal route is a good alternative for the
      resection of suprasellar lesions. It permits tumor resection and preservation of
      the surrounding neurovascular structures while avoiding external incisions and
      brain retraction. The link to the video can be found at:
      https://youtu.be/zmgxQe8w-JQ .

PMID- 29588887
TI  - Combined Interhemispheric and Transsylvian Approach for Resection of
      Craniopharyngioma.
AB  - We present a 37-year-old male case of cystic suprasellar huge craniopharyngioma,
      who presented with significant memory disturbance due to obstructive
      hydrocephalus. Combined interhemispheric and pterional approach was chosen to
      resect huge suprasellar tumor. Interhemispheric trans-lamina terminalis approach
      was quite effective to resect third ventricular tumor, while pterional approach
      was useful to dissect tumor out of basilar perforators and stalk. The link to the
      video can be found at: https://youtu.be/BoYIPa96kdo .

PMID- 29588888
TI  - Extended Endoscopic Endonasal Resection of a Suprasellar and Third Ventricular
      Retrochiasmatic Craniopharyngioma with a Narrow Pituitary Gland-Optic Chiasm
      Interval: Techniques to Optimize Resection.
AB  - The extended endoscopic endonasal approach can be utilized to surgically treat
      pathology within the suprasellar space. This relies on a sufficient corridor and
      interval between the superior aspect of the pituitary gland and the optic chiasm.
      Tumors located in the retrochiasmatic space and within the third ventricle,
      however, may not have a widened interval through which to work. With mass effect
      on the superior and posterior aspect of the optic chiasm, the corridor between
      the chiasm and the pituitary gland might even be further narrowed. This may
      negate the possibility of utilizing the endoscopic endonasal approach for the
      management of pathology in this location. We present a case of a retrochiasmatic
      craniopharyngioma with a narrow resection corridor that was treated with the
      extended endoscopic approach and we review techniques to potentially overcome
      this limitation. The link to the video can be found at: https://youtu.be/ogRZj
      aBqeQ .

PMID- 29588889
TI  - Orbitopterional Craniotomy Resection of Pediatric Suprasellar Craniopharyngioma.
AB  - The orbitopterional approach provides an excellent combination of basal access
      and suprasellar access. This approach also allows for less brain retraction when
      resecting larger suprasellar tumors that are more superiorly projecting due to a
      more frontal and inferior trajectory. In this operative video, the authors
      thoroughly detail an orbitopterional craniotomy utilizing a one-piece modified
      orbitozygomatic technique. This technique involves opening the craniotomy through
      a standard pterional incision. The craniotomy is performed using the standard
      three burr holes of a pterional approach; however, the osteotomy is extended
      anteriorly through the frontal process of the zygomatic bone as well as through
      the supraorbital rim. In this operative video atlas, the authors illustrate the
      operative anatomy, as well as surgical strategy and techniques to resect a large
      suprasellar craniopharyngioma in a 4-year-old male. Other reasonable approach
      options for a lesion of this size would include a standard pterional approach, a
      supraorbital approach, or expanded endoscopic transsphenoidal approach. The
      lesion was quite high and thus, the supraorbital approach may confine access to
      the superior portion of the tumor. While recognizing that some groups may have
      chosen the endoscopic expanded transsphenoidal approach for this lesion, the
      authors describe more confidence in achieving the goal of a safe and maximal
      resection with the orbitopterional approach. The link to the video can be found
      at: https://youtu.be/eznsK16BzR8 .

PMID- 29588890
TI  - Endoscopic Transsphenoidal Salvage Surgery for Symptomatic Residual Cystic
      Craniopharyngioma after Radiotherapy.
AB  - Objectives  Ideal treatment of craniopharyngiomas is still controversial.
      Radiotherapy (RT) is considered effective for recurrences or after subtotal tumor
      removal (STR). About 40 to 50% of patients may experience tumor cyst expansion
      soon after RT; in these cases, the role of salvage surgery is debated. Design 
      Operative video. Setting  Tertiary care center. Participants  An 11-year-old boy
      diagnosed with persistent craniopharyngioma. In 2015, the patient underwent right
      frontotemporal craniotomy for STR at another center, complicated by
      panhypopituitarism. Two years later, fractionated 54-Gy RT was performed on
      growing residual tumor. After 3 months, he was admitted to our hospital due to
      persistent malaise, vomiting, pulsating headache, and epistaxis. Ophthalmologic
      evaluation evidenced left homonymous hemianopsia. Results  A contrast-enhanced
      magnetic resonance imaging (MRI) showed a 27-mm cystic component enlarging from
      the cranial end of the persistent craniopharyngioma lesion, extending into the
      third ventricle. Biventricular hydrocephalus and brain midline shift to the right
      were present. Compared with the early post-RT MRI, the cystic component of the
      tumor demonstrated growth. The patient underwent external ventricular drainage
      placement for emergent treatment of hydrocephalus and endoscopic transsphenoidal
      surgery. After cystic content drainage, the lesion was completely removed with
      its capsule. A "gasket seal" technique was performed for skull base
      reconstruction, with autologous fascia lata, septal bone, and mucoperiosteum from
      inferior turbinate. Histologic examination confirmed the craniopharyngioma
      diagnosis. Postoperative MRI showed resolution of the hydrocephalus and complete
      tumor removal. Conclusion  Although shrinkage of cystic components of
      craniopharyngioma residuals may occur within 5 to 6 months after RT, salvage
      surgery is indicated in symptomatic patients. The link to the video can be found
      at https://youtu.be/4x6Qe76bf60 .

PMID- 29588891
TI  - Transcallosal, Transchoroidal Resection of a Recurrent Craniopharyngioma.
AB  - Objective  To demonstrate the transchoroidal approach for the resection of a
      recurrent craniopharyngioma. Design  Video case report. Setting  Microsurgical
      resection. Participant  The patient was a 27-year-old woman with a history of a
      craniopharyngioma, resected twice during the year prior to presentation to our
      unit. Both operations were done via the left anterolateral corridor, and
      afterward, she was blind in the left eye and was treated with Desmopressin
      (DDAVP) for diabetes insipidus (DI). Serial magnetic resonance imaging (MRI)
      showed progression of the tumor residual, and she was referred for further
      surgical intervention. Main Outcome Measures  Pre- and postoperative MRIs
      measured the degree of resection. Results  For this, her third surgery, a
      transcallosal, transchoroidal approach, was chosen to offer the widest possible
      exposure. Given her history, an aggressive total resection was the best strategy.
      The patient was placed supine with the head neutral. A right frontal craniotomy
      allowed access to the interhemispheric fissure. By opening the corpus callosum,
      the left lateral ventricle was entered. The transchoroidal approach started with
      dissection of the tenia fornicis to open the choroidal fissure. After this,
      sufficient exposure to the posterior parts of the tumor was gained. Resection
      proceeded to the bottom of the tumor, exposing the basilar apex and
      interpeduncular cistern, and continued back anteriorly. In the end, a microscopic
      total resection was achieved. With a long hospital stay to treat her brittle DI,
      the patient slowly returned to neurological baseline. Conclusion  The
      transchoroidal approach is an effective way to remove large tumors in the third
      ventricle. The link to the video can be found at: https://youtu.be/2-Aqjaay8dg .

PMID- 29588892
TI  - Orbitopterional Approach with Extradural Clinoidectomy for the Resection of a
      Tuberculum Sellae Meningioma: Adapting the Strategy to the Microsurgical and
      Pathological Anatomy.
AB  - Objectives  To describe the orbitopterional approach with extradural
      clinoidectomy for the resection of a tuberculum sellae meningioma, with an
      emphasis on the microsurgical and pathological anatomy of such lesions. Design 
      After completing the orbitopterional craniotomy in one piece, the optic nerve is
      identified extradurally, unroofed, and the clinoid process resected. The
      falciform ligament is divided and the optic nerve is decompressed extradurally.
      Opening the frontotemporal dura exposes the tumor in the subfrontal region. The
      tumor is followed along the ipsilateral and contralateral optic nerves, and its
      dural tail is cut and coagulated at the level of the tuberculum. Care is taken to
      preserve the optic nerve perforators during the dissection. Photographs of the
      region are borrowed from Dr Rhoton's laboratory to illustrate the microsurgical
      anatomy. Participants  The surgery was performed by the senior author assisted by
      Dr. Jaafar Basma, neurosurgery fourth-year resident. The video was edited by Dr.
      Vincent Nguyen, neurosurgery third-year resident. Outcome Measures  Outcome was
      assessed with the extent of resection and visual symptoms. Results  A near-total
      resection of the tumor was achieved. A small part of tumor significantly adherent
      to the optic nerve was intentionally left behind. The patient had a stable vision
      examination postoperatively. Conclusions  Understanding the microsurgical anatomy
      of the suprasellar region and the pathological anatomy of the tuberculum sellae
      meningioma is necessary to achieve a good resection of these tumors while
      preserving functionality of the optic apparatus. The orbitopterional approach
      with anterior clinoidectomy provides the appropriate access for such endeavor.
      The link to the video can be found at: https://youtu.be/WtAP8uqSW0M .

PMID- 29588893
TI  - Lateral Supraorbital Craniotomy for Tuberculum Sella Meningioma Resection.
AB  - Tuberculum sella meningioma can be approached by either open or endoscopic
      approaches. The aim of this video case presentation is to highlight the nuances
      of the lateral supraorbital craniotomy for tuberculum sella meningioma resection.
      The authors present a 34-year-old female patient who presented with decreased
      right eye visual acuity (20/60), afferent pupillary defect, and nasal field cut
      due to a tuberculum sella meningioma. The tumor was partially encasing the left
      A1 artery, severely displacing the optic apparatus, and minimally invading the
      right optic canal. The lateral supraorbital craniotomy was considered the most
      suitable approach to this tumor. The operative nuances and pitfalls of this
      approach are detailed in the video. Gross total resection of the tumor was
      achieved and confirmed with postoperative MRI. The patient's vision gradually
      improved and she was discharged on the fourth postoperative day. The minimally
      invasive lateral supraorbital craniotomy for tuberculum sella meningioma is a
      suitable approach in selected cases. The link to the video can be found at:
      https://youtu.be/yG8q6YH2D9k .

PMID- 29588894
TI  - Surgery of Tuberculum Sellae Meningioma: A Technical Purview on Pterional
      Approach.
AB  - Objective  Amidst the raging debate between transnasal and transcranial
      approaches, the critical factor that dictates success lies in the meticulous
      dissection of the tumor from the optic apparatus, anterior communicating artery
      complex, and the pituitary stalk. In this surgical video, we describe the
      resection of a tuberculum sellae meningioma through the pterional approach
      highlighting dissection through the appropriate arachnoidal plane. Case
      Description  The patient is a 75-year-old female who presented with optic nerve
      compression with bitemporal hemianopia and endocrine function abnormalities. A
      transcranial approach was done to effectively decompress the optic nerve. The
      video includes a detailed discussion on the surgical techniques including working
      between the different surgical corridors, working in the arachnoid plane to
      dissect the neurovascular structures away from the tumor, identification, and
      preservation of pituitary stalk. Postoperatively, the patient's visual field
      deficit improved with a remaining isolated right temporal field defect at 2
      months follow-up. Her endocrine function improved after the surgery. Conclusion 
      In the era of endoscopic surgery, transcranial approaches for suprasellar tumors
      like tuberculum sellae meningiomas still have a distinct surgical role. Our
      discussion extends to reiterate the strengths and weaknesses of the transcranial
      approach to this region as compared with the endoscopic approach. We believe
      decompression of optic nerves, separation of Acom complex from the tumor, and
      preservation of pituitary stalk are better achieved through a transcranial
      approach. The link to the video can be found at : https://youtu.be/kw5eP3oUd6Q .

PMID- 29588895
TI  - Expanded Endoscopic Transsphenoidal Resection of Tuberculum Sella Meningioma
      Invading the Optic Canal.
AB  - A 61-year-old male patient presented with recurrent malignant meningioma
      involving the left optic canal and decreased vision from the left eye. The
      patient had undergone orbital exenteration on the right 2 years ago. The decision
      to treat the patient was made based on the significant vision deterioration and
      rapid tumor growth. Endoscopic transsphenoidal approach considered the most
      suitable route due to the inferomedial invasion of the optic canal. Gross total
      removal was achieved and the patient's vision improved postoperatively. The
      patient developed hydrocephalus 4 weeks postoperatively and cerebrospinal fluid
      (CSF) leak. Ventriculoperitoneal shunt placement corrected both hydrocephalus and
      CSF leak. The link to the video can be found at: https://youtu.be/2cOF0pf5gAk .

PMID- 29588896
TI  - Endoscopic Endonasal Resection of Tuberculum Sellae Meningioma with Utilization
      of Indocyanine Green.
AB  - We present the case of a 67-year-old female with an incidental finding of a left
      sided tuberculum sellae meningioma on a brain magnetic resonance imaging (MRI)
      for an unrelated complaint. Formal visual field testing showed a small defect in
      the inferior nasal and temporal fields of the left eye, compatible with mass
      effect on the optic nerve by the tumor. An endoscopic endonasal transtuberculum
      approach with decompression of the left optic nerve was performed using a
      standard binostril four-hand technique, with the patient positioned supine with
      the head turned to the right side and tilted to the left, fixed in a three-pin
      head clamp, under imaging guidance. After exposure, we drilled the tuberculum
      sellae and the floor of the sella and after opening the dura, the tumor and optic
      nerve came into view. The tumor was completely removed and we confirmed the
      patency of all perforating vessels using indocyanine green. Reconstruction was
      done in a multilayered fashion, using collagen matrix and a nasoseptal flap.
      Patient had an uneventful postoperative stay and was discharged on postoperative
      day 3, neurologically stable with no new hormonal deficits. Pathology report
      confirmed a WHO Grade I meningioma with Ki -67 of 1% and 3-month postoperative
      MRI confirmed a gross total resection and visual fields exam showed a complete
      recovery. The link to the video can be found at: https://youtu.be/zRmt2aIvX5c .

PMID- 29588897
TI  - Endoscopic Endonasal Transplanum-Transtuberculum Sellae Approach for the
      Resection of a Diaphragma Sellae Meningioma.
AB  - The endoscopic endonasal approach (EEA) provides a direct access to diaphragma
      sellae meningiomas. We present a case of a 56-year-old-female with an
      incidentally diagnosed sellar/suprasellar lesion with no hormonal deficit; thus,
      she opted for conservative management initially. During her annual follow-up
      appointment with her ophthalmologist, it was noticed that the patient had right
      eye peripheral deficit on formal visual field testing. Magnetic resonance imaging
      (MRI) revealed an enlargement of the sellar/suprasellar mass, causing
      displacement of the optic chiasm. A transplanum-transtuberculum EEA was
      performed. Gross-total removal was achieved and closure was done in a multilayer
      fashion using a collagen matrix, nasoseptal flap. Histopathological examination
      confirmed a meningioma WHO grade I. There were no intra- or postoperative
      complications. At 4-year-follow-up, the patient has stable vision and MRI brain
      showed no recurrence. The link to the video can be found at:
      https://youtu.be/xY8T9hotlDs .

PMID- 29588898
TI  - Low Subfrontal Dural Opening for Anterior Clinoid Meningioma.
AB  - Introduction  A variety of dural openings are described for frontal-temporal and
      cranio-orbital craniotomies. As with any surgical technique, the goal is to
      optimally and safely address the pathology, minimize normal anatomy disruption,
      and optimize postoperative recovery. This study reports a modified dural opening
      for frontal-temporal approaches which minimizes brain exposure while facilitating
      visualization for neoplastic and vascular lesions of the anterior clinoid, supra-
      and parasellar and adjacent regions. Methods  A sample case is presented for
      which a low subfrontal dural exposure was utilized for tumor resection. The
      clinical presentation, surgical procedure, and outcome are summarized including a
      video detailing the surgical technique. Results  A 63-year-old female with
      gradual left eye vision loss and tumor enlargement on serial imaging. The small
      dural-based tumor arose from the left anterior clinoid and optic canal region
      compressing the optic nerve. The video shows a left frontal-temporal craniotomy
      used to perform extradural anterior clinoidectomy and optic canal decompression.
      The novel low subfrontal dural opening without fixed brain retraction allowed
      dural opening around the optic canal and clinoidectomy region to resect tumor and
      complete optic nerve decompression. Postoperatively, the patient did well with
      significant recovery of vision and follow-up at 2.5 years shows no evidence of
      tumor recurrence. Conclusion  The novel low subfrontal dural opening provides
      access to lesions of the supra-and para-sellar and adjacent regions, and
      preservation of much of the dura avoids some of the risks of intradural
      dissection including Sylvian fissure dissection and brain retraction The link to
      the video can be found at: https://youtu.be/Jc7wvR4PTFk .

PMID- 29588899
TI  - Combined Frontotemporal Transbasal Approach for the Resection of a Giant Rathke's
      Cleft Cyst: Operative Video and Technical Nuances.
AB  - We present a case of a giant Rathke's cleft cyst with significant superior
      extension into the third and right lateral ventricles and lateral extension into
      the left Sylvian fissure and over the anterior clinoid process. An extended
      modification of the frontotemporal approach was performed using a combined
      frontotemporal transbasal approach. This allowed wide exposure to both
      transsylvian and subfrontal corridors to the retrochiasmatic space. This video
      atlas demonstrates the operative technique and surgical nuances of the skull base
      approach, microdissection of the tumor, and safe handling of the neurovascular
      structures. A gross total resection was achieved and the patient was
      neurologically intact with improved visual acuity. In summary, the combined
      frontotemporal transbasal approach is an important strategy in the armamentarium
      for the surgical management of giant Rathke's cleft cysts. The link to the video
      can be found at: https://youtu.be/UjhnUZVi03I .

PMID- 29588900
TI  - Interhemispheric, Translamina Terminalis Approach for the Resection of
      Suprasellar Cavernous Malformation.
AB  - Objectives  The current video presents the nuances of an interhemispheric,
      translamina terminalis approach for the resection of suprasellar cavernous
      malformation. Design  The video analyzes the presentation, preoperative workup
      and imaging, surgical steps and technical nuances of the surgery, the clinical
      outcome, and follow-up imaging. Setting  The patient was treated by a skull base
      team at a teaching academic institution. Participants  The case refers to a 64
      year-old female who presented with vision loss and confusion, and was found to
      have a suprasellar mass, with imaging characteristics consistent with a cavernous
      malformation of the third ventricle. Main Outcome Measures  The main outcome
      measures consist of the reversal of the patient symptoms (vision loss and
      confusion), the recurrence-free survival based on imaging, as well as the absence
      of any complications. Results  The patient's mental status improved slightly
      after surgery. There was no evidence of recurrence. Conclusions  The
      interhemispheric, translamina terminalis approach is safe and effective for the
      resection of suprasellar cavernous malformations. The link to the video can be
      found at: https://youtu.be/z6RSAM_GnBA .

PMID- 29588901
TI  - Endoscopic Endonasal Transtuberculum Sellae Approach for the Resection of
      Suprasellar Intrainfundibular Epidermoid Cyst.
AB  - A 49-year-old female presented with intense headaches of 3 months duration. Brain
      magnetic resonance imaging (MRI) was performed and showed a sellar-suprasellar
      lesion extending into the third ventricle. A presumptive diagnosis of a
      craniopharyngioma was made. Since the patient did not have any visual deficits,
      she opted for conservative management. Four months later, she started to have
      progressive deterioration of vision; thus, surgery was indicated. The patient
      underwent endoscopic endonasal resection of the lesion through a transtuberculum
      sellae approach. The patient was positioned supine with the head slightly
      extended and the face turned to the right side. Following the essence of a
      binostril four-hand technique, a total gross resection of the lesion was achieved
      and multilayer skull base reconstruction was performed utilizing collagen matrix
      and nasoseptal flap; with no intraoperative complications. The patient's
      postoperative course was uneventful with the improvement in her vision, and she
      was discharged on postoperative day 4 with no new neurological deficits.
      Histopathological examination confirmed the diagnosis of an epidermoid cyst.
      Postoperative pituitary gland function was within normal limits except for mild
      diabetes insipidus for which she is on DDAVP 0.1 mg twice daily. At 4 years
      follow-up, the patient was doing well, her vision was normalized, and brain MRI
      revealed no evidence of residual or recurrent lesion. The link to the video can
      be found at: https://youtu.be/OqDFpa_Xq78 .

PMID- 29588902
TI  - Gross Total Resection of Chordoid Glioma of the Third Ventricle via Anterior
      Interhemispheric Transcallosal Transforaminal Approach at Two Stages.
AB  - Suprasellar tumors in particular tumors located in the retrochiasmatic area and
      anterior third ventricle are challenging cases in terms of optimal surgical
      exposure. Several approaches have been described including transsylvian,
      translamina terminalis, endoscopic endonasal, and anterior interhemispheric. Each
      approach has advantages and disadvantages. In this video, we present a case of
      retrochiasmatic anterior third ventricular tumor that was operated via anterior
      interhemispheric transcallosal transforaminal approach. The patient is a 42-year
      old female who presented with sudden onset of severe headache and depressed level
      of consciousness. Computed tomography (CT) scan of the head showed a hemorrhage
      in the third ventricle and suprasellar cisterns. CT angiogram and magnetic
      resonance imaging (MRI) confirmed diagnosis of hemorrhagic mass lesion in the
      third ventricle. Upon further questioning of her family, we found out that she
      was having excessive urination and short-term memory problems for last 2 weeks.
      First, ventriculostomy was placed for obstructive hydrocephalus. She then
      underwent surgical resection via anterior interhemispheric transcallosal
      transforaminal approach. Foramen of Monro was enlarged by performing
      transchoroidal dissection. Using transforaminal route, tumor was resected. Due to
      the narrow surgical corridor and high vascularity of the tumor, decision was made
      to come back at a second stage. Using same surgical approach, in the second
      stage, gross total resection was performed. Postoperative MRI confirmed gross
      total resection. Histopathology was chordoid glioma of the third ventricle. She
      made excellent recovery with persistent diabetes insipidus. Currently, she is
      completing radiation therapy. In this video, we demonstrate techniques and
      pitfalls of anterior interhemispheric transcallosal approach to anterior third
      ventricular tumor. The link to the video can be found at:
      https://youtu.be/CI5c6Zup8sY .

PMID- 29588903
TI  - Endoscopic Endonasal Transoculomotor Triangle Approach for the Resection of a
      Pituitary Adenoma with Ambient Cistern Extension.
AB  - Objectives  The current video presents the nuances of the endoscopic endonasal
      transoculomotor triangle approach for the resection of a pituitary adenoma with
      extension into the ambient cistern. Design  The video analyzes the presentation,
      preoperative workup and imaging, surgical steps and technical nuances of the
      surgery, the clinical outcome, and follow-up imaging. Setting  The patient was
      treated by a skull base team consisting of a neurosurgeon and an ENT surgeon at a
      teaching academic institution. Participants  The case refers to a 62-year-old
      female who presented with vision loss and headaches, and was found to have a
      pituitary adenoma with extension into the ambient cistern. Main Outcome Measures 
      The main outcome measures consist of the reversal of the patient symptoms
      (headaches), the recurrence-free survival based on imaging, as well as the
      absence of any complications. Results  The patient's headaches improved. There
      was no evidence of recurrence. Conclusions  The endoscopic endonasal
      transoculomotor triangle approach is safe and effective for addressing pituitary
      tumors which extend into the ambient cistern. The link to the video can be found
      at: https://youtu.be/EBLwEWhohxY .

PMID- 29588904
TI  - Endoscopic Endonasal Approach for Complex Macroadenoma with Suprasellar and
      Retrochiasmatic Extension.
AB  - In this video, we describe the technical nuances of an endoscopic endonasal
      approach (EEA) for a complex macroadenoma with suprasellar and retrochiasmatic
      extension. The patient is a 51-year-old male with several years' history of
      progressive visual loss. Neuro-ophthalmology assessment revealed a profound
      visual loss with homonymous hemianopsia and left optic nerve atrophy. His
      pituitary hormonal profile was normal. The options for surgical approach included
      transcranial, endoscopic endonasal, or a combination of both. An EEA was the
      preferred surgical option, because it allows for early identification of the
      pituitary gland, and provides access to the suprasellar region including pre- and
      retrochiasmatic spaces, which facilitates tumor removal while minimizing
      manipulation of the optic apparatus. While most pituitary adenomas do not require
      extracapsular subarachnoidal dissection, there are complex adenomas with
      subarachnoidal invasion and multilobulated morphology, such as the one presented
      here, that require a combination of internal debulking, extracapsular and
      subarachnoidal dissection. The technique presented here allows for complete tumor
      resection, avoiding the risk of postoperative apoplexy of residual adenoma, and
      facilitates identification of perforating branches and neural structures that
      require meticulous preservation. Here, we also illustrate the proper management
      of reconstruction-related complications. Postoperative course was complicated
      with meningitis with necrotic nasoseptal flap and required surgical debridement,
      new inferior turbinate flap, fascia lata, lumbar drain, and 6-week antibiotic
      treatment. Imaging follow-up showed complete removal of tumor. The patient had
      significant improvement in visual fields and left visual acuity, and no
      postoperative hormonal dysfunction. The link to the video can be found at:
      https://youtu.be/9T5b167bVJA .

PMID- 29588905
TI  - Endoscopic Endonasal Resection of a Suprasellar Pituitary Adenoma Mimicking
      Tuberculum Sellae Meningioma in a Patient with an Intrasellar Persistent
      Trigeminal Artery.
AB  - A 50-year-old female with an incidentally diagnosed suprasellar lesion was
      initially managed conservatively due to the presence of an intrasellar persistent
      trigeminal artery going through the dorsum sellae and fundamentally forming the
      blood supply of the entire posterior circulation. Serial follow-up brain magnetic
      resonance imaging (MRI) revealed progressive enlargement of the suprasellar
      lesion over 4 years period. Surgery was indicated after the initial tumor growth;
      however, the patient refused surgery for fear of complications related to the
      persistent trigeminal artery. Two-and-a-half years later, she presented with
      deterioration of vision. Formal visual field testing revealed a right temporal
      field defect. Brain MRI demonstrated significantly enlarged suprasellar lesion,
      most consistent with tuberculum sellae meningioma, exerting mass effect on the
      optic apparatus. The patient underwent endoscopic endonasal resection of the
      lesion through a transplanum/transtuberculum approach. Intraoperatively, absence
      of hypertrophic McConnel arteries, hyperostosis, and the fact that the dura was
      soft and not under tension was against the diagnosis of tuberculum sellae
      meningioma. Additionally, the tumor consistency was similar to a pituitary
      adenoma. A complete resection was accomplished and multilayer skull base
      reconstruction was performed with no complications. On postoperative day 1 (POD
      1), she was operated upon for the evacuation of small suprasellar hematoma
      associated with vision deterioration. Histopathological examination confirmed the
      diagnosis of atypical pituitary adenoma with Ki -67 labeling index of 4 to 5%.
      The patient ultimately recovered well with improved vision, and was discharged on
      POD 4 with no new neurological deficits. At 4 years follow-up, her vision was
      normalized and brain MRI showed no residual or recurrent lesion. The link to the
      video can be found at: https://youtu.be/QZmzctjAEbw .

PMID- 29588906
TI  - Complications of Extended Endoscopic Endonasal Surgery in Elderly Patients.
AB  - Extended endoscopic endonasal procedures are not unique among surgical
      interventions in carrying increased risk in the elderly population. There are,
      however, components of the procedure, namely high-flow cerebrospinal fluid leaks,
      that do result in the potential for increased perioperative morbidity for these
      patients. We present the case of a 77-year-old male with a large invasive
      pituitary macroadenoma resected through a transplanum-transtuberculum-transsellar
      endonasal approach. A gross total resection was obtained with resolution of the
      patient's preoperative ophthalmologic deficits. One month postoperatively, the
      patient developed progressive lethargy and cranial imaging demonstrated a left
      convexity subacute subdural hematoma. This was evacuated through a twist drill
      craniostomy. Despite measures to limit the operative time of the initial
      endonasal procedure as well as the absence of a postoperative cerebrospinal fluid
      fistula, the patient still developed this complication. Along with more typical
      potential causes of postoperative decline following extended endonasal
      procedures, problems from high-flow intraoperative cerebrospinal fluid leaks
      alone can result in morbidity in the elderly population. This should be
      acknowledged preoperatively and a high suspicion should exist for the presence of
      intracranial hemorrhage in these patients with any postoperative deficits.
      Additional intraoperative measures can be utilized to minimize such risks. The
      link to the video can be found at: https://youtu.be/EkLmt2T8_UE .

PMID- 29588908
TI  - Autopsy kidneys: an overlooked resource.

PMID- 29588907
TI  - Disseminated toxoplasmosis in a patient with advanced acquired immunodeficiency
      syndrome.
AB  - Extracerebral toxoplasmosis, with pulmonary involvement and shock, is a rare form
      of toxoplasmosis in patients with advanced AIDS. It can mimic pneumocystosis,
      histoplasmosis, and disseminated tuberculosis, and should be considered in the
      differential diagnosis of causes of respiratory failure and fulminant disease in
      this group of individuals, especially in areas where the Toxoplasma gondii
      infection is highly prevalent and in those without proper use of antimicrobial
      prophylaxis. We report the case of a 46-year-old male patient who presented to
      the emergency department with uremia, requiring urgent dialysis. During the
      laboratorial investigation, the patient had confirmed HIV infection, with a low
      CD4+ peripheral T-cell count (74 cells/uL). During hospitalization, the patient
      presented drug-induced hepatitis due to trimethoprim/sulfamethoxazole in a
      prophylactic dose, requiring interruption of this medication. On the 55th day of
      hospitalization, the patient developed refractory shock and died. At the autopsy,
      disseminated toxoplasmosis with encephalitis and severe necrotizing pneumonia
      were diagnosed, with numerous tachyzoites in the areas of pulmonary necrosis.

PMID- 29588909
TI  - Muehrcke's lines.

PMID- 29588910
TI  - Effect of the masseter muscle injection of botulinum toxin A on the mandibular
      bone growth of developmental rats.
AB  - Background: The objective of this study was to evaluate the influence of
      masticatory muscle injection of botulinum toxin type A (BTX-A) on the growth of
      the mandibular bone in vivo. Methods: Eleven Sprague-Dawley rats were used, and
      BTX-A (n = 6) or saline (n = 5) was injected at 13 days of age. All injections
      were given to the right masseter muscle, and the BTX-A dose was 0.5 units. All of
      the rats were euthanized at 60 days of age. The skulls of the rats were separated
      and fixed with 10% formalin for micro-computed tomography (micro-CT) analysis.
      Results: The anthropometric analysis found that the ramus heights and bigonial
      widths of the BTX-A-injected group were significantly smaller than those of the
      saline-injected group (P < 0.05), and the mandibular plane angle of the BTX-A
      injected group was significantly greater than in the saline-injected group (P <
      0.001). In the BTX-A-injected group, the ramus heights II and III and the
      mandibular plane angles I and II showed significant differences between the
      injected and non-injected sides (P < 0.05). The BTX-A-injected side of the
      mandible in the masseter group showed significantly lower mandibular bone growth
      compared with the non-injected side. Conclusion: BTX-A injection into the
      masseter muscle influences mandibular bone growth.

PMID- 29588911
TI  - Intimate Partner Violence Among Transgender Youth: Associations with
      Intrapersonal and Structural Factors.
AB  - Intimate partner violence (IPV) is a serious public health problem, linked with a
      number of poor health outcomes. Some research demonstrates that transgender and
      gender nonconforming (TGNC) youth may experience IPV at similar rates to
      heterosexual cisgender women; however, there is a dearth of data examining the
      experiences of IPV among this population. The exclusion of TGNC youth in IPV
      research and public health interventions is problematic because it contributes to
      a traditional gender-based heterosexual model of IPV that ignores the specific
      needs of TGNC populations. Given the pervasiveness of transphobic stigma in the
      United States and the complexities of the lives of TGNC youth, it is important to
      understand how both structural and individual factors are associated with IPV
      among TGNC youth. Using data from a cross-sectional survey of 131 TGNC youth from
      14 different cities in the United States representing various regions of the
      country, this study explores the associations between a range of structural and
      intrapersonal factors and experiences of IPV victimization among TGNC youth.
      Separate logistic regression models were fit to examine the relationships between
      structural and intrapersonal factors and IPV. Structural results found that TGNC
      youth experiencing extreme victimization, a history of incarceration, and
      participation in sex work were much more likely to report IPV. The only
      intrapersonal variable that was associated with IPV was depressive
      symptomatology; however, this relationship was strong, with participants being
      nearly eight times more likely to report IPV if they experienced symptoms of
      depression. Gaining a better understanding of the complexity of both structural
      and intrapersonal factors among TGNC youth will greatly inform the development of
      IPV prevention and services for TGNC youth experiencing this type of violence.

PMID- 29588914
TI  - Association of ACL Laxity Tests with Arthroscopic Findings in Chronic ACL and PCL
      Deficient Knees.
AB  - An anterior cruciate ligament (ACL) injury may be diagnosed by clinical
      examination and radiological investigation using magnetic resonance imaging or by
      arthroscopy. 1,2 Based on our experience, the ACL tear in concomitant chronic ACL
      and posterior cruciate ligament (PCL) deficient knees may produce knee laxity,
      which is more difficult to assess on clinical examination, which in turn may
      affect the management algorithm of the patient. Our hypothesis is that, in a
      concomitant chronic ACL and PCL injury, posterior capsular contracture and
      abnormal reattachment of torn ACL will result in less clinical and subjective
      laxity, preoperatively. The aim of this study is to review a cohort of patients
      who had undergone PCL reconstructive surgery and compare the preoperative
      clinical assessments with and without anesthesia with arthroscopic finding of
      ACL. This is to assess the accuracy and reliability of clinical ACL laxity tests
      in detecting ACL tear in chronic ACL and PCL injury.

PMID- 29588912
TI  - Changes Over Time in Nasopharyngeal Colonization in Children Under 2 Years of Age
      at the Time of Diagnosis of Acute Otitis Media (1999-2014).
AB  - Background: In children with acute otitis media (AOM), a decrease in
      nasopharyngeal (NP) colonization with vaccine serotypes of Streptococcus
      pneumoniae has been noted since the introduction of pneumococcal conjugate
      vaccines (PCVs). The purpose of this study is to describe corresponding changes
      in colonization with Haemophilus influenzae. Methods: In 4 separate studies, we
      obtained NP cultures from children aged 6-23 months presenting with AOM. Cohort 1
      was recruited before routine use of PCV7 (1999-2000); 93% of children in cohort 2
      (2003-2005) and 100% in cohort 3 (2006-2009) received >=2 doses of PCV7. All
      children in cohort 4 (2012-2014) received >=2 doses of PCV13. Isolates of H.
      influenzae were tested for beta-lactamase production; beta-lactamase negative
      isolates from cohorts 3 and 4 underwent susceptibility testing. Results: A total
      of 899 children were evaluated. NP colonization with H. influenzae was found in
      26% of children in cohort 1 (n = 175), 41% in cohort 2 (n = 87), 33% in cohort 3
      (n = 282), and 29% in cohort 4 (n = 355). Colonization with H. influenzae
      increased initially from cohort 1 to cohort 2 (P = .01), then decreased across
      cohorts 2, 3, and 4 (P = .03, test for trend). The prevalence rates of beta
      lactamase production were 27%, 42%, 33%, and 30% in each of the 4 cohorts,
      respectively (P = .50). Conclusions: Although an initial increase in H.
      influenzae colonization was observed, suggesting an impact of PCVs, the most
      recent prevalence rates of NP colonization with H. influenzae and beta-lactamase
      production were like those observed before universal administration of PCV7. This
      knowledge is critical to guide appropriate treatment recommendations for children
      with AOM.

PMID- 29588913
TI  - Dynamics of Colonization of Streptococcus pneumoniae Strains in Healthy Peruvian
      Children.
AB  - Background: Although asymptomatic carriage of Streptococcus pneumoniae (Spn) is
      common, acquisition of the bacteria is the first step in disease pathogenesis. We
      examined the effect of introduction of the 7-valent pneumococcal vaccine on Spn
      carriage patterns in a cohort of Peruvian children. Methods: We used data from a
      prospective cohort study that collected monthly nasopharyngeal samples from
      children under 3 years of age. Spn isolates were serotyped using Quellung
      reactions, and bacterial density was determined by quantitative polymerase chain
      reaction. Changes in Spn carriage patterns, including the rate of carriage and
      number and density of serotypes carried over time, were evaluated before (2009)
      and after widespread vaccination with PCV7 (2011). Using all pneumococcal
      detections from each child and year, we identified serotypes that were present
      both at first and last detection as "persisters" and serotypes that replaced a
      different earlier type and were detected last as "recolonizers." Results: Ninety
      two percent (467/506) of children in 2009 and 89% (451/509) in 2011 carried Spn
      at least once. In 2009 and 2011, rates of carriage were 9.03 and 9.04 Spn
      detections per person-year, respectively. In 2009, 23F, a serotype included in
      PCV7, was the only type identified as a persister and 6A, 15B, and 19A were
      identified as recolonizer serotypes. In 2011, 6B and 7C were persister serotypes
      and 13 was a frequent recolonizer serotype. Conclusions: Overall Spn carriage
      among children under 3 in Peru was similar before and after introduction of PCV7;
      however, serotype-specific rates and longitudinal carriage patterns have shifted.

PMID- 29588916
TI  - Medicinal Cannabis on Prescription in The Netherlands: Statistics for 2003-2016.

PMID- 29588915
TI  - Recurrent 8-Year Ongoing Unilateral Breast Seroma Formation after PIP Implant
      Removal-A Case Report and Review of the Literature.
AB  - Late seroma formation is a rare complication after implant-based breast
      enlargement surgery and even less frequent after implant removal. This case
      report presents a case of painful recurrent seroma formation after the removal of
      a ruptured Poly Implants Prothese implant. A 52-year-old patient presented
      herself in our clinic with a clinical history of recurrent unilateral seroma of
      the right breast over a period of 8 years after the initial unilateral implant
      removal. Removal of the remaining implant and complete bilateral capsulectomy was
      performed. Intraoperative findings revealed a macroscopically thickened capsule
      with signs of chronic inflammation on the affected side. The clinical history and
      the macroscopic appearance of the capsule demanded histopathological exclusion of
      a possible anaplastic large cell lymphoma. Histopathological and microbiological
      analysis of the capsule and encapsulated material revealed no signs of malignancy
      or infection. Immediate soft tissue reconstruction of the breast was successfully
      performed using autologous fat transfer. An aesthetically satisfying result
      regarding symmetry and volume was achieved, and no further seroma formation was
      observed within a 6-month follow-up period. Level of evidence:  V, Case Report.

PMID- 29588917
TI  - A National Needs Assessment of Canadian Nurse Practitioners Regarding Cannabis
      for Therapeutic Purposes.
AB  - Introduction: In Canada, the Access to Cannabis for Medical Purposes Regulations
      (ACMPR) has given nurse practitioners (NPs) the power to authorize cannabis for
      therapeutic purposes (CTP) to eligible patients. This expansion in NPs' scope of
      practice underscores the importance of delivering balanced, evidence-based
      education on cannabis to NPs. The aim of this national study was to assess NPs'
      knowledge and practice gaps related to CTP to inform the development of future
      education resources that increase NPs' clinical competence and improve patient
      care related to medical cannabis. Methods: This is a quantitative, descriptive
      exploratory design study. A national online survey of NPs was conducted from
      August 2013 to June 2014. NPs were recruited through email lists held by numerous
      Canadian nursing organizations. The survey was adapted from a previous national
      survey that assessed CTP educational needs among Canadian physicians. The survey
      assessed NPs' knowledge, experience, barriers, and attitudes related to CTP as
      well as preferred format for future CTP education. Results: The sample consisted
      of 182 NPs from across Canada. The largest knowledge gap was related to dosing
      and creating effective treatment plans for patients using CTP. The majority of
      respondents (76.3%) ranked the need for education on CTP to be either strong or
      very strong. Over half (57%) reported that they would be comfortable authorizing
      medical cannabis through the ACMPR; this number increased to 64% if they were to
      receive appropriate education. Conclusion: Nursing regulatory organizations, in
      partnership with academic institutions and government agencies, must work toward
      the development of educational and clinical competencies specific to CTP.
      Tailored education programs are needed to address the knowledge gaps held by NPs
      and the clinical barriers they face to including CTP as part of their care.

PMID- 29588918
TI  - Percutaneous and Endoscopic Management of Nephrolithiasis in a Patient with Five
      Native Ureters (Trifid Right and Bifid Left Collecting System).
AB  - Triplication of the ureter is a rare urologic finding that has been well
      described in the literature. Patients can present with urinary tract infections,
      incontinence, and calculi. We present the case of a patient with extensive stone
      burden with right trifid and left bifid collecting systems. Stone management was
      performed with a multimodal approach using a combination of endoscopic and
      percutaneous approaches. Our systematic and staged approach highlights a method
      for efficacious stone treatment in a complex endourologic case.

PMID- 29588919
TI  - Laparoscopic Surgery for Seminal Vesicle Cysts and Ureterocele with Urination
      Disorder: A Case Report of Zinner Syndrome.
AB  - Background: Zinner syndrome is defined as seminal vesicle cysts with ipsilateral
      renal agenesis and an ectopic ureter. Symptomatic cases are very rare. In this
      article, we present a laparoscopic approach for a case of Zinner syndrome. Case
      Presentation: The patient was a 21-year-old male with difficult urination. A
      right seminal vesicle cyst and right kidney agenesis associated with ureterocele
      were found on examination and he was diagnosed with Zinner syndrome. First, we
      performed transperineal puncture of the ureterocele because it closed the bladder
      neck during voiding. Although voiding symptoms temporarily improved, the
      ureterocele recurred soon and the urination disorder was reexacerbated. Next, we
      selected laparoscopic removal of the ureterocele and the seminal vesicle cyst.
      The procedure was performed with transperitoneal access using four trocars.
      Perioperative and postoperative complications were not observed, and micturition
      was satisfactory after surgery. Conclusion: Treatment for difficult urination
      because of Zinner syndrome is mostly selected puncture of the ureterocele or
      seminal vesicle cyst. However, some patients experience recurrence. The
      laparoscopic approach is minimally invasive and provides a satisfactory surgical
      field. Therefore, it should be considered the method of treatment for symptomatic
      Zinner syndrome.

PMID- 29588920
TI  - Optimisation of ex vivo memory B cell expansion/differentiation for interrogation
      of rare peripheral memory B cell subset responses.
AB  - Background: Human memory B cells play a vital role in the long-term protection of
      the host from pathogenic re-challenge. In recent years the importance of a number
      of different memory B cell subsets that can be formed in response to vaccination
      or infection has started to become clear. To study memory B cell responses, cells
      can be cultured ex vivo, allowing for an increase in cell number and activation
      of these quiescent cells, providing sufficient quantities of each memory subset
      to enable full investigation of functionality. However, despite numerous papers
      being published demonstrating bulk memory B cell culture, we could find no
      literature on optimised conditions for the study of memory B cell subsets, such
      as IgM + memory B cells. Methods: Following a literature review, we carried out a
      large screen of memory B cell expansion conditions to identify the combination
      that induced the highest levels of memory B cell expansion. We subsequently used
      a novel Design of Experiments approach to finely tune the optimal memory B cell
      expansion and differentiation conditions for human memory B cell subsets.
      Finally, we characterised the resultant memory B cell subpopulations by IgH
      sequencing and flow cytometry. Results: The application of specific optimised
      conditions induce multiple rounds of memory B cell proliferation equally across
      Ig isotypes, differentiation of memory B cells to antibody secreting cells, and
      importantly do not alter the Ig genotype of the stimulated cells.  Conclusions:
      Overall, our data identify a memory B cell culture system that offers a robust
      platform for investigating the functionality of rare memory B cell subsets to
      infection and/or vaccination.

PMID- 29588921
TI  - Characterisation of innate lymphoid cell populations at different sites in mice
      with defective T cell immunity.
AB  - Background: Innate lymphoid cells (ILCs) have now been identified within most
      tissues of the body and current evidence indicates that this family of cells play
      a fundamental role in maintaining tissue homeostasis. However, few studies have
      compared the ILC populations between several tissues. Methods: We sought to
      generate a comprehensive characterisation of the ILC populations in different
      tissues of C57BL/6 WT and genetically modified mice targeting costimulatory
      pathways, using transcription factor expression to define specific groups.
      Results: Consistent with studies individually describing the ILC composition in
      different tissues, our analysis revealed different ILC groups dominate the ILC
      population in different tissues. Additionally, we observed a population of  IL
      7Ralpha +Id2 + cells lacking expression of lineage markers but also lacking
      expression of GATA-3, RORgt or T-bet. This population was most evident in ear
      skin where it outnumbered the defined ILC groups, however, further experiments
      demonstrated that detection of these cells was influenced by how the tissue was
      digested, raising concerns as to its real nature. Since both ILC2 and ILC3
      express ICOS, we then investigated the requirement for ICOS:ICOSL interactions in
      the homeostasis of ILC populations at these sites. Surprisingly, no significant
      differences were detected in the number of ILC1, ILC2 or ILC3 between WT and
      ICOSL -/- mice in any tissue, indicating that this pathway is not required for
      ILC homeostasis at these sites. These data were compared with CD80 -/-CD86 -/-
      mice given evidence of CD28 expression by some ILC and ILC crosstalk with
      activated T cells. Notably, the absence of CD28 ligands resulted in a significant
      increase in ILC2 and ILC3 numbers in the intestine. Conclusions: Together, these
      data provide new insight into ILC composition in different tissues in both WT and
      genetically modified mice where key costimulatory pathways are genetically
      deleted, providing a useful resource for further research into ILC biology.

PMID- 29588922
TI  - Clinical signs of trachoma are prevalent among Solomon Islanders who have no
      persistent markers of prior infection with Chlamydia trachomatis.
AB  - Background: The low population-prevalence of trachomatous trichiasis and high
      prevalence of trachomatous inflammation-follicular (TF) provide contradictory
      estimates of the magnitude of the public health threat from trachoma in the
      Solomon Islands. Improved characterisation of the biology of trachoma in the
      region may support policy makers as they decide what interventions are required.
      Here, age-specific profiles of anti-Pgp3 antibodies and conjunctival scarring
      were examined to determine whether there is evidence of ongoing transmission and
      pathology from ocular Chlamydia trachomatis (Ct) infection. Methods: A total of
      1511 individuals aged >=1 year were enrolled from randomly selected households in
      13 villages in which >10% of children aged 1-9 years had TF prior to a single
      round of azithromycin mass drug administration undertaken six months previously.
      Blood was collected to be screened for antibodies to the Ct antigen Pgp3. Tarsal
      conjunctival photographs were collected for analysis of scarring severity.
      Results: Anti-Pgp3 seropositivity was 18% in 1-9 year olds, sharply increasing
      around the age of sexual debut to reach 69% in those over 25 years. Anti-Pgp3
      seropositivity did not increase significantly between the ages of 1-9 years and
      was not associated with TF (p=0.581) or scarring in children (p=0.472).
      Conjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not
      severe (p=0.149) scars increased in prevalence with age. Conclusions: Neither
      conjunctival scars nor lymphoid follicles were associated with antibodies to Ct,
      suggesting that they are unlikely to be a direct result of ocular Ct infection .
      Clinical signs of trachoma were prevalent in this population but were not
      indicative of the underlying rates of Ct infection. The current World Health
      Organization guidelines for trachoma elimination indicated that this population
      should receive intervention with mass distribution of antibiotics, but the data
      presented here suggest that this may not have been appropriate.

PMID- 29588923
TI  - Why Epilepsia Open?

PMID- 29588924
TI  - Commentary: Message from the ILAE president.

PMID- 29588925
TI  - Not all that glitters is gold: A guide to the critical interpretation of drug
      trials in epilepsy.
AB  - Clinical trials represent the best source of evidence on which to base treatment
      decisions. For such evidence to be utilized meaningfully, however, it is
      essential that results are interpreted correctly. This requires a good
      understanding of strengths and weaknesses of the adopted design, the clinical
      relevance of the outcome measures, and the many factors that could affect such
      outcomes. As a general rule, uncontrolled studies tend to provide misleading
      evidence as a result of the impact of confounders such as regression to the mean,
      patient-related bias, and observer bias. On the other hand, although randomized
      controlled trials (RCTs) are qualitatively superior, aspects of their execution
      may still decrease their validity. Bias and decreased validity in RCTs may occur
      by chance alone (for example, treatment groups may not necessarily be balanced
      for important variables despite randomization) or because of specific features of
      the trial design. In the case of industry-driven studies, bias often influences
      the outcome in favor of the sponsor's product. Factors that need to be carefully
      scrutinized include (1) the purpose for which the trial is conducted; (2)
      potential bias due to unblinding or lack of blinding; (3) the appropriateness of
      the control group; (4) the power of the study in detecting clinically relevant
      differences; (5) the extent to which eligibility criteria could affect outcomes
      and be representative of routine clinical practice; (6) whether the treatments
      being compared are used optimally in terms of dosing, duration of treatment, and
      other variables; (7) the appropriateness of the statistical comparisons; (8) the
      clinical relevance of the outcome measures and whether all key outcome
      information is reported (for example, responder rates in completers); and (9)
      potential bias in the way results are presented and discussed. This article
      discusses each of these aspects and illustrates the discussion with examples
      taken from published antiepileptic drug trials.

PMID- 29588926
TI  - Not all that glitters is gold: A guide to surgical trials in epilepsy.
AB  - Epilepsy surgery is often the only effective treatment in appropriately selected
      patients with drug-resistant epilepsy, a disease affecting about 30% of those
      with epilepsy. We review the evidence supporting the use of epilepsy surgery,
      with a focus on randomized controlled trials (RCTs). Second, we identify gaps in
      knowledge about the benefits of epilepsy surgery for certain populations, the
      challenges of individualizing the choice of surgery, and our lack of
      understanding of the mechanisms of surgical outcomes. We conducted a search
      (MEDLINE, Embase, Cochrane, Clinicaltrials.gov) on March 2, 2016, to identify
      epilepsy surgery RCTs, systematic reviews, or health technology assessments
      (HTAs). Abstracts were screened to identify resective, palliative (e.g., corpus
      callosotomy, multiple subpial transection [MST]), ablative (e.g., Laser
      interstitial thermal therapy [LITT], gamma knife radiosurgery [RS]), and
      neuromodulation (e.g., cerebellar stimulation [CS], hippocampal stimulation [HS],
      repetitive transcranial magnetic stimulation [rTMS], responsive neurostimulation
      [RNS], thalamic stimulation [TS], trigeminal nerve stimulation [TNS], and vagal
      nerve stimulation [VNS]) RCTs. Study characteristics and outcomes were extracted.
      Knowledge gaps were identified. Of 1,205 abstracts, 20 RCTs were identified
      (resective surgery including corpus callosotomy [n = 7], MST [n = 0], RS [n = 1,
      3 papers], LITT [n = 0], CS [n = 1], HS [n = 2], RNS [n = 1], rTMS [n = 1], TNS
      [n = 1], TS [n = 1], and VNS [n = 5]). Most studies targeted patients with
      temporal lobe epilepsy (TLE) and none examined the effectiveness of resective
      surgical therapies in patients with extra-TLE (ETLE) or with specific lesions
      aside from mesial temporal lobe sclerosis. No pediatric surgical RCTs were
      identified except for VNS. Few RCTs address the effectiveness of surgery in
      epilepsy and most are of limited generalizability. Future studies are needed to
      compare the effectiveness of different surgical strategies, better understand the
      mechanisms of surgical outcomes, and define the ideal surgical approaches,
      particularly for patients with high or very low cognitive function, normal
      imaging, or ETLE.

PMID- 29588927
TI  - Classification of the epilepsies: New concepts for discussion and debate-Special
      report of the ILAE Classification Task Force of the Commission for Classification
      and Terminology.
AB  - The ILAE Task Force on Classification presents a road map for the development of
      an updated, relevant classification of the epilepsies. Our objective is to
      explain the process to date and the plan moving forward as well as to invite
      further discussion about the newly proposed terms and concepts. Here, we present
      our response to feedback about the 2010 Organization of the Epilepsies and
      clarify the reintroduction of the word "classification" to map out a framework
      for epilepsy diagnosis. We introduce some new concepts and suggest four
      diagnostic levels: seizure type, epilepsy category, epilepsy syndrome, and
      epilepsy with (specific) etiology to denote specific levels of diagnosis. We
      expand the etiological categories to six, focusing on those with treatment
      implications. Finally, we discuss the changes in terminology originally suggested
      and modifications in response to comments from the epilepsy community. We welcome
      feedback and discussion from the global epilepsy community, particularly for the
      new suggested terms, so that we can cement a classification that both reflects
      current thinking and scientific understanding and provides a dynamic, evolving
      framework.

PMID- 29588928
TI  - The effects of carbamazepine in the intrahippocampal kainate model of temporal
      lobe epilepsy depend on seizure definition and mouse strain.
AB  - Objective: Mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis is a
      predominant form of acquired epilepsy, characterized by recurrent simple and
      complex partial seizures that are often resistant to treatment. Mice developing
      spontaneous recurrent nonconvulsive and convulsive seizures after
      intrahippocampal injection of the excitotoxic glutamate agonist kainate are
      thought to represent a valuable model of mesial TLE. Epileptic
      electroencephalogram (EEG) activity recorded in this model from the kainate focus
      in the ipsilateral hippocampus is resistant to antiseizure drugs such as
      carbamazepine (CBZ). We compared the efficacy of CBZ in this model in two
      different mouse strains (FVB/N and NMRI). Furthermore, we evaluated whether
      changes in the definition of electrographic seizures affect the antiseizure
      efficacy of CBZ. Methods: As in previous studies, two types of epileptic EEG
      activity were defined: high-voltage sharp waves (HVSWs) and hippocampal
      paroxysmal discharges (HPDs). The characteristics of these paroxysmal EEG events
      in epileptic mice were compared with EEG criteria for nonconvulsive seizures in
      patients. For HVSWs, different spike frequencies, interevent intervals, and
      amplitudes were used as inclusion and exclusion criteria. In addition to CBZ,
      some experiments were performed with diazepam (DZP) and phenobarbital (PB).
      Results: Female epileptic FVB/N mice predominantly exhibited frequent HVSWs, but
      only infrequent HPDs or secondarily generalized convulsive seizures. Slight
      changes in HVSW definition determined whether they were resistant or responsive
      to CBZ. Male NMRI mice exhibited both HVSWs and HPDs. HVSWs were more resistant
      than HPDs to suppression by CBZ. Both types of epileptic EEG activity were
      rapidly suppressed by DZP and PB. Significance: The data demonstrate that focal
      electrographic seizures in the intrahippocampal kainate mouse model are less
      resistant than previously thought. Both mouse strain and the criteria chosen for
      definition of EEG seizures determine whether such seizures are drug-resistant or 
      responsive.

PMID- 29588929
TI  - Long-term mortality of patients with West syndrome.
AB  - Objective: To study long-term survival and mortality among patients with West
      syndrome. Methods: The study population included all children born in 1960-1976
      and treated for West syndrome in three tertiary care hospitals in Helsinki,
      Finland. The participants were prospectively followed for five decades for
      survival. Death data were derived from the National Causes of Death Register of
      the Population Register Center of Statistics Finland. Results: During follow-up,
      102 (49%) of 207 patients had died at the mean age of 19 years. The mean overall
      annual mortality rate was 15.3 per 1,000 patient-years. The rates ranged from
      18.2 per 1,000 after 10 years to 17.2 per 1,000 after 20 years and 15.4 per 1,000
      patient-years after 40 years of follow-up. One fourth (25%) had died by 17.2 (95%
      CI 11.8-22.7) years and 50% by 48.6 (95% CI 38.5-NA) years of follow-up. Etiology
      at onset was symptomatic in 87% patients and cryptogenic in 13%; 6 of the latter
      26 patients later turned out to be symptomatic. The mean annual mortality rate
      was 3.7 per 1,000 for 4 patients with cryptogenic etiology and 17.6 per 1,000 for
      those with symptomatic etiology. The hazard of death was fivefold in patients
      with symptomatic etiology versus cryptogenic etiology. The overall autopsy rate
      was 73%. Pneumonia was the most frequent cause of death (46%). All patients who
      died of pneumonia had symptomatic etiology. SUDEP occurred in 10 patients and was
      the most common epilepsy-related cause of death (10%). Significance: Risk of
      excess death of participants with West syndrome is not limited to early age but
      continues into adulthood, particularly in those with symptomatic etiology, and
      leads to death in half the cases at around 50 years of age. Measures should be
      directed to prevent pneumonia, the most common overall cause, and SUDEP, the most
      frequent seizure-related cause, of death.

PMID- 29588931
TI  - Minimizing publication bias in Epilepsia Open: Negative or confirmatory studies
      and preliminary reports.

PMID- 29588932
TI  - The right and the wrong with epilepsy and her science.
AB  - This is a commentary and an opinion paper attempting a critical reassessment of
      the methods and practices of epilepsy research as we see it. The enormous
      progress in the field of epilepsy in recent years is a cause of celebration.
      Advances have been made on most fronts, and the position of patients with
      epilepsy in society has greatly improved. However, there have also been culs-de
      sac and dead ends of modern science and clinical practice which are also
      intriguing. It may be true that we can learn more from our mistakes than from our
      successes. In this opinion paper, we have listed some of the successes and some
      of the failures of past epilepsy practice, and also areas of current practice and
      theory which we feel are likely to prove mistaken. The underlying reasons for
      misdirected practices and theories include, in our view, the influence of
      fashion, bad science, and the bureaucracies of practice and academic medicine. As
      a result, some findings are far from objective. Recognition is the first step to
      remediation, and hopefully future research will minimize some of the pitfalls
      mentioned in this article and bring the "End of Epilepsy," as defined and
      predicted by Oswei Temkin, closer than it is today.

PMID- 29588933
TI  - Behavioral disorder in people with an intellectual disability and epilepsy: A
      report of the Intellectual Disability Task Force of the Neuropsychiatric
      Commission of ILAE.
AB  - The management and needs of people with intellectual disability (ID) and epilepsy
      are well evidenced; less so, the comorbidity of behavioral disorder in this
      population. "Behavioral disorder" is defined as behaviors that are difficult or
      disruptive, including stereotypes, difficult or disruptive behavior, aggressive
      behavior toward other people, behaviors that lead to injury to self or others,
      and destruction of property. These have an important link to emotional
      disturbance. This report, produced by the Intellectual Disability Task Force of
      the Neuropsychiatric Commission of the ILAE, aims to provide a brief review of
      some key areas of concern regarding behavioral disorder among this population and
      proposes a range of research and clinical practice recommendations generated by
      task force members. The areas covered in this report were identified by experts
      in the field as being of specific relevance to the broad epilepsy community when
      considering behavioral disorder in persons with epilepsy and ID; they are not
      intended to be exhaustive. The practice recommendations are based on the authors'
      review of the limited research in this field combined with their experience
      supporting this population. These points are not graded but can be seen as expert
      opinion guiding future research and clinical practice.

PMID- 29588934
TI  - Risk of convulsive epilepsy following acute seizures in Kenyan children.
AB  - Objective: The prevalence of epilepsy is high in Africa, and people with epilepsy
      often have a history of acute seizures. We determined whether acute seizures are
      associated with risk for epilepsy in rural Africa, where both conditions are
      common and may have shared risk factors. Methods: A total of 16,438 children
      (2,991 with acute seizures and 13,447 without seizures) admitted to Kilifi County
      Hospital from 2002 to 2008 were followed up with epidemiological surveys
      conducted in 2003 and 2008 to assess the prevalence of epilepsy and the
      associated risk factors. Cox proportional hazards regression models were used to
      identify the risk factors. Prevalence ratios were computed using log binomial
      regression models. Results: The prevalence of epilepsy was higher in admissions
      with acute seizures (5.0% [95% confidence interval (CI), 4.3-5.9%]) than in those
      without seizures (0.7% [95% CI, 0.5-0.8%]), p < 0.0001). Acute seizures were
      associated with epilepsy after accounting for potential confounders in a Cox
      regression model (hazard ratio [HR] = 1.53 [95% CI, 1.10-2.14]). Prevalence was
      greater in complex acute seizures (5.9%; prevalence ratio [PR] = 1.58 [95% CI,
      1.13-2.20]) or status epilepticus (7.5%; PR = 1.96 [95% CI, 1.32-2.91]) than in
      simple acute seizures (3.7%). Factors independently associated with epilepsy
      following acute seizures in Cox regression models were perinatal complications
      (HR = 3.60 [95% CI, 1.89-6.87]), cerebral palsy (HR = 1491.51 [95% CI, 144.30
      15,416.21]), duration of follow-up (HR = 1.21 [95% CI, 1.09-1.35]), and
      malnutrition (relative risk [RR] = 0.24 [95% CI, 0.08-0.69]). Significance: Acute
      seizures in children are associated with subsequent risk for epilepsy that is
      greater than in the general population. The burden of epilepsy may be reduced by
      control of causes of acute seizures.

PMID- 29588935
TI  - A study on spike focus dependence of high-frequency activity in idiopathic focal
      epilepsy in childhood.
AB  - Objective: Spike foci in benign epilepsy with centrotemporal spikes (BECTS) are
      related to seizure semiologies, but this relationship is inconspicuous in
      Panayiotopoulos syndrome (PS). We analyzed spike-associated high-frequency
      activity (HFA) and its relationship to spike foci in the electroencephalograms
      (EEGs) of patients with BECTS and PS in order to elucidate the pathophysiology of
      these epileptic syndromes. Methods: In 35 patients with BECTS and 29 with PS,
      focal spikes in scalp sleep EEGs were first classified by clustering according to
      their characteristics, including shape and distribution. For each patient, three
      or fewer spike clusters were investigated by time-frequency spectral analysis and
      single-dipole analysis using a realistic three-dimensional head model to explore
      the relationships between the presence or absence of spike-associated HFA and the
      distribution of estimated spike sources. Results: A total of 159 spike clusters
      were analyzed (96 in BECTS and 63 in PS). HFA was detected in 73 spike clusters
      (76.0%) in BECTS and 37 (58.7%) in PS, with a significant difference in the
      proportion of spike clusters with HFA (p = 0.024 by Fisher's exact test). In
      BECTS, spikes had relatively uniform distributions, but the proportion of spikes
      with associated HFA was significantly higher in the spike group with dipoles in
      the perirolandic areas (42 of 49) than in that with dipoles outside of the
      perirolandic areas (23 of 36; p = 0.037). In PS, The proportion of spikes with
      associated HFA was significantly higher in the spike group with dipoles in the
      occipital lobes (20 of 26) than in that with dipoles outside of the occipital
      lobes (13 of 33; p = 0.020). Significance: The proportion of spike-associated HFA
      was higher in BECTS than in PS. Particular pathophysiological meaning was
      indicated in spikes with dipoles in the perirolandic areas in BECTS and in spikes
      with dipoles in the occipital lobes in PS owing to the high proportions of spike
      associated HFA in these areas.

PMID- 29588936
TI  - Cathodal transcranial direct-current stimulation for treatment of drug-resistant
      temporal lobe epilepsy: A pilot randomized controlled trial.
AB  - Objective: To investigate the effect of cathodal transcranial direct-current
      stimulation (c-tDCS) on seizure frequency in patients with drug-resistant
      temporal lobe epilepsy (TLE). Method: Twenty-nine patients with drug-resistant
      TLE participated in this study. They were randomized to experimental or sham
      group. Twenty participants (experimental group) received within-session repeated
      c-tDCS intervention over the affected temporal lobe, and nine (sham group)
      received sham tDCS. Paired-pulse transcranial magnetic stimulation was used to
      assess short interval intracortical inhibition (SICI) in primary motor cortex
      ipsilateral to the affected temporal lobe. SICI was measured from motor evoked
      potentials recorded from the contralateral first dorsal interosseous muscle.
      Adverse effects were monitored during and after each intervention in both groups.
      A seizure diary was given to each participant to complete for 4 weeks following
      the tDCS intervention. The mean response ratio was calculated from their seizure
      rates before and after the tDCS intervention. Results: The experimental group
      showed a significant increase in SICI compared to the sham group (F = 10.3, p =
      0.005). None of the participants reported side effects of moderate or severe
      degree. The mean response ratio in seizure frequency was -42.14% (standard
      deviation [SD] 35.93) for the experimental group and -16.98% (SD 52.41) for the
      sham group. Significance: Results from this pilot study suggest that tDCS may be
      a safe and efficacious nonpharmacologic intervention for patients with drug
      resistant TLE. Further evaluation in larger double-blind randomized controlled
      trials is warranted.

PMID- 29588937
TI  - Unusual Course of Lafora Disease.
AB  - A 42-year-old male was admitted for refractory status epilepticus. At the age of
      25, he had been diagnosed with juvenile myoclonic epilepsy. He had a stable
      clinical course for over a decade until a recent deterioration of behavior and
      epilepsy. After exclusion of acquired disorders, diagnostic work-up included
      application of next-generation sequencing (NGS), with a gene panel targeting
      progressive myoclonic epilepsies. This resulted in the diagnosis Lafora disease
      resulting from compound heterozygous NHLRC1 pathogenic variants. Although these
      pathogenic variants may be associated with a variable phenotype, including both
      severe and mild clinical course, the clinical presentation of our patient at this
      age is very unusual for Lafora disease. Our case expands the phenotype spectrum
      of Lafora disease resulting from pathogenic NHLRC1 variants and illustrates the
      value of using NGS in clinical practice to lead to a rapid diagnosis and guide
      therapeutic options.

PMID- 29588938
TI  - Partial deletion of DEPDC5 in a child with focal epilepsy.
AB  - We report on a child, aged 47/12 years, with borderline intelligence quotient,
      normal brain magnetic resonance imaging, and focal epilepsy. The polysomnographic
      electroencephalogram recording revealed asynchronous central spikes at both brain
      hemispheres resembling the features observed in focal idiopathic epileptic
      syndromes. Array comparative genomic hybridization analysis revealed a 32-kb
      partial deletion of the DEP domain-containing protein 5 (DEPDC5) gene, involved
      in a wide spectrum of inherited focal epileptic syndromes. The parental origin of
      the deletion could not be fully ascertained because the pregnancy had been
      achieved through anonymous egg donation and insemination by intracytoplasmic
      sperm injection. However, we demonstrate that the deletion, shared by all
      alternatively spliced isoforms of DEPDC5, produces a transcript presumably
      generating a DEPDC5 protein missing the entire DEP domain. Our findings suggest
      that partial deletion of DEPDC5 may be sufficient to cause the focal epilepsy in
      our patient, highlighting the importance of the DEP domain in DEPDC5 function.
      This study expands the phenotypic spectrum of DEPDC5 to sporadic forms of focal
      idiopathic epilepsy and underscores the fact that partial deletions, albeit
      probably very rare, are part of the genetic spectrum of DEPDC5 mutations.

PMID- 29588939
TI  - Cannabis in epilepsy: From clinical practice to basic research focusing on the
      possible role of cannabidivarin.
AB  - Cannabidivarin (CBDV) and cannabidiol (CBD) have recently emerged among
      cannabinoids for their potential antiepileptic properties, as shown in several
      animal models. We report the case of a patient affected by symptomatic partial
      epilepsy who used cannabis as self-medication after the failure of countless
      pharmacological/surgical treatments. Clinical and video electroencephalogram
      (EEG) evaluations were periodically performed, and the serum levels of CBDV, CBD,
      and Delta9-tetrahydrocannabinol were repeatedly measured. After cannabis
      administration, a dramatic clinical improvement, in terms of both decrease in
      seizure frequency and recovery of cognitive functions, was observed, which might
      parallel high CBDV plasma concentrations. To widen the spectrum of CBDV possible
      mechanisms of action, electrophysiological methods were applied to investigate
      whether it could exert some effects on gamma-aminobutyric acid (GABA)A receptors.
      Our experiments showed that, in human hippocampal tissues of four patients
      affected by drug-resistant temporal lobe epilepsy (TLE) transplanted in Xenopus
      oocytes, there is decrease of current rundown (i.e., reduction of use-dependent
      GABAA current) after prolonged exposure to CBDV. This result has been confirmed
      using a single case of Rasmussen encephalitis (RE). Our patient's electroclinical
      improvement supports the hypothesis that cannabis could actually represent an
      effective, well-tolerated antiepileptic drug. Moreover, the experimental data
      suggest that CBDV may greatly contribute to cannabis anticonvulsant effect
      through its possible GABAergic action.

PMID- 29588941
TI  - Improving clinical trial efficiency: Is technology the answer?

PMID- 29588943
TI  - Onchocerciasis-associated epilepsy: From recent epidemiological and clinical
      findings to policy implications.
AB  - A high prevalence of epilepsy is reported in many onchocerciasis-endemic regions.
      In this paper we discuss recent epidemiological and clinical aspects as well as
      public health implications of onchocerciasis-associated epilepsy (OAE) and
      propose a strategy to reduce the burden of disease. OAE probably presents in a
      variety of clinical manifestations, including the nodding syndrome and the
      Nakalanga syndrome. The most common clinical presentation, however, is
      generalized (primarily tonic-clonic) seizures. A characteristic of OAE is the
      onset of seizures between the ages of 3 and 18 years and clustering in certain
      families and villages close to rapid-flowing black-fly-infested rivers. A
      strategy combining active surveillance for epilepsy with early treatment with
      antiepileptic drugs and prevention of onchocerciasis by increasing the
      geographical and therapeutic coverage of community-directed treatment with
      ivermectin (CDTi) may considerably decrease the burden of disease.

PMID- 29588944
TI  - Defeating epilepsy: A global public health commitment.
AB  - This article points out that defeating epilepsy is a global public health
      commitment and a new challenge. This is because: epilepsy causes a heavy burden
      and very high treatment gap; in the field of life sciences and medicine, the 21st
      century would be the "Century of Brain Science"; a number of national brain
      research initiatives provide a great opportunity to reveal the secret of
      epilepsy; the Global Campaign against Epilepsy and the Mental Health Gap Action
      Programme made great contributions in the epilepsy control work worldwide; the
      historical WHA68.20 resolution gives great strength to promote defeating
      epilepsy.

PMID- 29588942
TI  - Management of post-traumatic epilepsy: An evidence review over the last 5 years
      and future directions.
AB  - Post-traumatic epilepsy (PTE) is a relatively underappreciated condition that can
      develop as a secondary consequence following traumatic brain injury (TBI). The
      aim of this rapid evidence review is to provide a synthesis of existing evidence
      on the effectiveness of treatment interventions for the prevention of PTE in
      people who have suffered a moderate/severe TBI to increase awareness and
      understanding among consumers. Electronic medical databases (n = 5) and gray
      literature published between January 2010 and April 2015 were searched for
      studies on the management of PTE. Twenty-two eligible studies were identified
      that met the inclusion criteria. No evidence was found for the effectiveness of
      any pharmacological treatments in the prevention or treatment of symptomatic
      seizures in adults with PTE. However, limited high-level evidence for the
      effectiveness of the antiepileptic drug levetiracetam was identified for PTE in
      children. Low-level evidence was identified for nonpharmacological interventions
      in significantly reducing seizures in patients with PTE, but only in a minority
      of cases, requiring further high-level studies to confirm the results. This
      review provides an opportunity for researchers and health service professionals
      to better understand the underlying pathophysiology of PTE to develop novel, more
      effective therapeutic targets and to improve the quality of life of people with
      this condition.

PMID- 29588945
TI  - Seven tesla MRI improves detection of focal cortical dysplasia in patients with
      refractory focal epilepsy.
AB  - Objective: The aim of this study is to determine whether the use of 7 tesla (T)
      MRI in clinical practice leads to higher detection rates of focal cortical
      dysplasias in possible candidates for epilepsy surgery. Methods: In our center
      patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no
      abnormalities are detected at one or more previous, sufficient-quality lower
      field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed
      pathology is suspected in combination with MR-visible mesiotemporal sclerosis
      dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for
      presurgical evaluation and whose scans (both 7 T and lower field) were discussed
      during multidisciplinary epilepsy surgery meetings that included a dedicated
      epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary
      visual assessments of 7 T and lower-field MRI scans. Results: In our series of 40
      patients, multidisciplinary evaluation of 7 T MRI identified additional lesions
      not seen on lower-field MRI in 9 patients (23%). These findings were guiding in
      surgical planning. So far, 6 patients underwent surgery, with histological
      confirmation of focal cortical dysplasia or mild malformation of cortical
      development. Significance: Seven T MRI improves detection of subtle focal
      cortical dysplasia and mild malformations of cortical development in patients
      with intractable epilepsy and may therefore contribute to identification of
      surgical candidates and complete resection of the epileptogenic lesion, and thus
      to postoperative seizure freedom.

PMID- 29588946
TI  - Effective withdrawal of antiepileptic drugs in premonitoring admission to capture
      seizures during limited video-EEG monitoring.
AB  - Objective: Withdrawal of antiepileptic drugs (AEDs) is commonly applied to
      capture seizures in video-EEG (vEEG) monitoring for patients with infrequent but
      intractable seizures. Because of the half-life of AEDs, AED withdrawal during
      only vEEG tends to be inadequate to provoke seizures within the vEEG admission.
      We hypothesize that prewithdrawal of long-half-life AEDs in premonitoring
      admission (PMA) is safe and effective to capture seizures in the limited time of
      vEEG. We determined the effect of half-life on the interval between AED
      withdrawal and seizure occurrence. Methods: We collected 87 patients with three
      criteria: (1) seizure occurrence <=3 per month; (2) AEDs >=2; (3) AED withdrawal
      during their admission, among 126 consecutive patients who underwent vEEG in the
      Department of Neurosurgery, Hiroshima University Hospital between 2011 and 2014.
      We divided patients into two groups on the basis of half-life of AED: Group A (23
      patients) with phenobarbital (PB) and/or zonisamide (ZNS); Group B (64 patients)
      with other AEDs. In Group A, PB and ZNS were withdrawn during 4-day PMA before
      vEEG started. Further AED withdrawal was performed during vEEG, depending on the
      seizure occurrence. Results: The number of AEDs on admission was significantly
      higher in Group A (2-6, 3.5 +/- 0.9; range, mean +/-SD) than in Group B (2-5, 2.8
      +/- 0.8) (p < 0.01). All 23 Group A patients and 13 (20%) Group B patients
      underwent AED withdrawal during PMA. Seizures occurred during PMA in two patients
      in both Group A (9%) and Group B (15%). The first seizure occurred significantly
      longer after the start of withdrawal in Group A (6.1 +/- 2.0 days) than in Group
      B (2.8 +/- 1.3 days) (p < 0.01). Seizures were equally captured between both
      groups: 96% in Group A and 92% in Group B during vEEG. Significance: For epilepsy
      patients who are treated with PB and/or ZNS, we recommend the planning of AED
      withdrawal during PMA before the start of vEEG to succeed in capturing seizures
      during the limited time of vEEG monitoring.

PMID- 29588947
TI  - The intrahippocampal kainate mouse model of mesial temporal lobe epilepsy: Lack
      of electrographic seizure-like events in sham controls.
AB  - Objective: There is an ongoing debate about definition of seizures in
      experimental models of acquired epilepsy and how important adequate sham controls
      are in this respect. For instance, several mouse and rat strains exhibit high
      voltage rhythmic spike or spike-wave discharges in the cortical
      electroencephalogram (EEG), which has to be considered when using such strains
      for induction of epilepsy by status epilepticus, traumatic brain injury, or other
      means. Mice developing spontaneous recurrent nonconvulsive and convulsive
      seizures after intrahippocampal injection of kainate are increasingly being used
      as a model of mesial temporal lobe epilepsy. We performed a prospective study in
      which EEG alterations occurring in this model were compared with the EEGs in
      appropriate sham controls, using hippocampal electrodes and video-EEG monitoring.
      Methods: Experiments with intrahippocampal kainate (or saline) injections started
      when mice were about 8 weeks of age. Continuous video-EEG recording via
      hippocampal electrodes was performed 6 weeks after surgery in kainate-injected
      mice and sham controls, that is, at an age of about 14 weeks. Three days of
      continuous video-EEG monitoring were compared between kainate-injected mice and
      experimental controls. Results: As reported previously, kainate-injected mice
      exhibited two types of highly frequent electrographic seizures: high-voltage
      sharp waves, which were often monomorphic, and polymorphic hippocampal paroxysmal
      discharges. In addition, generalized convulsive clinical seizures were
      infrequently observed. None of these electrographic or electroclinical seizures
      were observed in sham controls. The only infrequently observed EEG abnormalities
      in sham controls were isolated spikes or spike clusters, which were also recorded
      in epileptic mice. Significance: This study rigorously demonstrates, by explicit
      comparison with the EEGs of sham controls, that the nonconvulsive paroxysmal
      events observed in this model are consequences of the induced epilepsy and not
      features of the EEG expected to be seen in some experimental control mice or
      unintentionally induced by surgical procedures.

PMID- 29588949
TI  - Understanding the burden of focal epilepsy as a function of seizure frequency in
      the United States, Europe, and Brazil.
AB  - Objective: To understand the current burden of focal epilepsy (FE) as a function
      of seizure frequency. Methods: Patients were identified from the United States
      (2011, 2012, and 2013), five European countries (EU; France, Germany, Italy,
      Spain, United Kingdom) (2011 and 2013), and Brazil (2011 and 2012) National
      Health and Wellness Survey (NHWS), a nationally representative, Internet-based
      survey of adults (18+ years). The NHWS collected data on respondents' quality of
      life (QoL), health utilities, productivity loss, and healthcare resource
      utilization. Indirect and direct costs were calculated from the literature.
      Altogether, 345 of 176,093 (U.S.A.), 73 of 30,000 (United Kingdom), 53 of 30,001
      (Germany), 53 of 30,000 (France), 41 of 12,011 (Spain), 37 of 17,500 (Italy), and
      71 of 24,000 (Brazil) respondents self-reported a diagnosis of FE. Results: Many
      respondents (U.S.A.: 56.2%; 5EU: 41.6%; Brazil + 5EU: 40.5%) reported persistent
      seizures (>=1 per year). Over 60% to just over 71% of respondents with FE were
      treated with antiepileptic drugs (AEDs). In the United States, seizure frequency
      was associated with hospitalizations, indirect costs (ages 18-60), and total
      direct costs. For the 5EU and Brazil + 5EU, seizure frequency was associated with
      physical QoL, health utilities, activity impairment, and emergency room (ER)
      visits. Additional associations were observed for the 5EU on hospitalizations,
      indirect costs (ages 18-60), ER visit costs, and total direct costs and for
      Brazil + 5EU on absenteeism, overall work impairment, and provider visits.
      Costing was not performed for Brazil + 5EU. Significance: Around half of the
      patients had persistent seizures despite most taking an AED in this 2011-2013
      dataset. The results support the hypothesis that reducing seizures can improve
      productivity and reduce resource utilization and associated costs. Regional
      differences may reflect differences in healthcare systems and selected patient
      populations. Overall, the results suggest that additional treatment options are
      needed to improve seizure control and reduce related costs.

PMID- 29588948
TI  - Adverse perinatal events, treatment gap, and positive family history linked to
      the high burden of active convulsive epilepsy in Uganda: A population-based
      study.
AB  - Objective: To determine the prevalence of active convulsive epilepsy (ACE) and
      describe the clinical characteristics and associated factors among a rural
      Ugandan population. Methods: The entire population in Iganga/Mayuge Health
      Demographic Surveillance Site (IM-HDSS) was screened using two questions about
      seizures during a door-to-door census exercise. Those who screened positive were
      assessed by a clinician to confirm diagnosis of epilepsy. A case control study
      with the patients diagnosed with ACE as the cases and age/sex-matched controls in
      a ratio of 1:1 was conducted. Results: A total of 64,172 (92.8%) IM-HDSS
      residents, with a median age of 15.0 years (interquartile range [IQR]: 8.0-29.0),
      were screened for epilepsy. There were 152 confirmed ACE cases, with a prevalence
      of 10.3/1,000 (95% confidence interval [CI]: 9.5-11.1) adjusted for nonresponse
      and screening sensitivity. Prevalence declined with age, with the highest
      prevalence in the 0-5 years age group. In an analysis of n = 241 that included
      cases not identified in the survey, nearly 70% were unaware of their diagnosis.
      Seizures were mostly of focal onset in 193 (80%), with poor electroencephalogram
      (EEG) agreement with seizure semiology. Antiepileptic drug use was rare, noted in
      21.2% (95% CI: 16.5-25.8), and 119 (49.3%) reported using traditional medicines.
      History of an abnormal antenatal period (adjusted odds ratio [aOR] 10.28; 95%CI
      1.26-83.45; p = 0.029) and difficulties in feeding, crying, breathing in the
      perinatal period (aOR 10.07; 95%CI 1.24-81.97; p = 0.031) were associated with
      ACE in children. In adults a family history of epilepsy (aOR 4.38 95%CI 1.77
      10.81; p = 0.001) was the only factor associated with ACE. Significance: There is
      a considerable burden of epilepsy, low awareness, and a large treatment gap in
      this population of rural sub-Saharan Africa. The identification of adverse
      perinatal events as a risk factor for developing epilepsy in children suggests
      that epilepsy burden may be decreased by improving obstetric and postnatal care.

PMID- 29588950
TI  - Decreased functional connectivity within a language subnetwork in benign epilepsy
      with centrotemporal spikes.
AB  - Objective: Benign epilepsy with centrotemporal spikes (BECTS, also known as
      Rolandic epilepsy) is a common epilepsy syndrome that is associated with literacy
      and language impairments. The neural mechanisms of the syndrome are not known.
      The primary objective of this study was to test the hypothesis that functional
      connectivity within the language network is decreased in children with BECTS. We
      also tested the hypothesis that siblings of children with BECTS have similar
      abnormalities. Methods: Echo planar magnetic resonance (MR) imaging data were
      acquired from 25 children with BECTS, 12 siblings, and 20 healthy controls, at
      rest. After preprocessing with particular attention to intrascan motion, the mean
      signal was extracted from each of 90 regions of interest. Sparse, undirected
      graphs were constructed from adjacency matrices consisting of Spearman's rank
      correlation coefficients. Global and nodal graph metrics and subnetwork and
      pairwise connectivity were compared between groups. Results: There were no
      significant differences in graph metrics between groups. Children with BECTS had
      decreased functional connectivity relative to controls within a four-node
      subnetwork, which consisted of the left inferior frontal gyrus, the left superior
      frontal gyrus, the left supramarginal gyrus, and the right inferior parietal lobe
      (p = 0.04). A similar but nonsignificant decrease was also observed for the
      siblings. The BECTS groups had significant increases in connectivity within a
      five-node, five-edge frontal subnetwork. Significance: The results provide
      further evidence of decreased functional connectivity between key mediators of
      speech processing, language, and reading in children with BECTS. We hypothesize
      that these decreases reflect delayed lateralization of the language network and
      contribute to specific cognitive impairments.

PMID- 29588951
TI  - Magnitude and factors associated with nonadherence to antiepileptic drug
      treatment in Africa: A cross-sectional multisite study.
AB  - Objectives: The epilepsy treatment gap is large in low- and middle-income
      countries, but the reasons behind nonadherence to treatment with antiepileptic
      drugs (AEDs) across African countries remain unclear. We investigated the extent
      to which AEDs are not taken and associated factors in people with active
      convulsive epilepsy (ACE) identified in cross-sectional studies conducted in five
      African countries. Methods: We approached 2,192 people with a confirmed diagnosis
      of ACE for consent to give blood voluntarily. Participants were asked if they
      were taking AEDs, and plasma drug concentrations were measured using a
      fluorescence polarization immunoassay analyzer. Information about possible risk
      factors was collected using questionnaire-based clinical interviews. We
      determined factors associated with nonadherence to AED treatment in children and
      adults, as measured by detectable and optimal levels, using multilevel logistic
      regression. Results: In 1,303 samples assayed (43.7% were children), AEDs were
      detected in 482, but only 287 had optimal levels. Of the 1,303 samples, 532
      (40.8%) were from people who had reported they were on AEDs. The overall
      prevalence of nonadherence to treatment was 63.1% (95% confidence interval [CI]
      60.5-65.6%) as measured by detectable AED levels and 79.1% (95% CI 73.3-84.3%) as
      measured by optimal AED levels; self-reported nonadherence was 65.1% (95% CI 45.0
      79.5%). Nonadherence was significantly (p < 0.001) more common among the children
      than among adults for optimal and detectable levels of AEDs, as was the self
      reported nonadherence. In children, lack of previous hospitalization and learning
      difficulties were independently associated with nonadherence to treatment. In
      adults, history of delivery at home, absence of burn marks, and not seeking
      traditional medicine were independently associated with the nonadherence to AED
      treatment. Significance: Only about 20% of people with epilepsy benefit fully
      from antiepileptic drugs in sub-Saharan Africa, according to optimum AEDs levels.
      Children taking AEDs should be supervised to promote compliance.

PMID- 29588952
TI  - Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic
      encephalopathy.
AB  - Objective: Epileptic encephalopathy (EE) is a heterogeneous condition associated
      with deteriorations of cognitive, sensory and/or motor functions as a consequence
      of epileptic activity. The phenomenon is the most common and severe in infancy
      and early childhood. Genetic-based diagnosis in EE patients is challenging owing
      to genetic and phenotypic heterogeneity of numerous monogenic disorders and the
      fact that thousands of genes are involved in neurodevelopment. Therefore, high
      throughput next-generation sequencing (NGS) was used to investigate the genetic
      causes of non-syndromic cryptogenic neonatal/infantile EE (NIEE). Methods: We
      have selected a cohort of 31 patients with seizure cryptogenic NIEE and seizure
      onset before 24 months. All investigations including metabolic work-up, were
      negative. Using NGS, we distinguished a panel of 430 epilepsy-associated genes by
      NGS was utilized to identify possible pathogenic variants in the patients.
      Segregation analysis and multiple silico analysis prediction tools were used for
      pathogenicity assessment. The identified variants were classified as
      "pathogenic," "likely pathogenic" and "uncertain significance," according to the
      American College of Medical Genetics (ACMG) guidelines. Results: Pathogenic or
      likely pathogenic variants were identified in six genes (ALG13 [1], CDKL5 [2],
      KCNQ2 [2], PNPO [1], SCN8A [1], SLC9A6 [2]) in 9 NIEE patients (9/31; 29%).
      Variants of uncertain significance (VUS) were found in DNM1 and TUBA8 in 2 NIEE
      patients (2/31; 6%). Most phenotypes in our cohort matched with those reported
      cases. Significance: The diagnostic rate (29%) of pathogenic and likely
      pathogenic variants was comparable to the recent studies of early-onset epileptic
      encephalopathy, indicating that gene panel analysis through NGS is a powerful
      tool to investigate cryptogenic NIEE in patients. Six percent of patients had
      neurometabolic disorders. Some of our diagnosed cases illustrated that successful
      molecular investigation may allow a better treatment strategy and avoid
      unnecessary and even invasive investigations. Functional analysis could be
      performed to further study the pathogenicity of the VUS identified in DNM1 and
      TUBA8.

PMID- 29588953
TI  - Copy number variation in a hospital-based cohort of children with epilepsy.
AB  - Objective: To evaluate the diagnostic yield of microarray analysis in a hospital
      based cohort of children with seizures and to identify novel candidate genes and
      susceptibility loci for epilepsy. Methods: Of all children who presented with
      their first seizure in the University Medical Center Groningen (January 2000
      through May 2013) (n = 1,368), we included 226 (17%) children who underwent
      microarray analysis before June 2014. All 226 children had a definite diagnosis
      of epilepsy. All their copy number variants (CNVs) on chromosomes 1-22 and X that
      contain protein-coding genes and have a prevalence of <1% in healthy controls
      were evaluated for their pathogenicity. Results: Children selected for microarray
      analysis more often had developmental problems (82% vs. 25%, p < 0.001), facial
      dysmorphisms (49% vs. 8%, p < 0.001), or behavioral problems (41% vs. 13%, p <
      0.001) than children who were not selected. We found known clinically relevant
      CNVs for epilepsy in 24 of the 226 children (11%). Seventeen of these 24 children
      had been diagnosed with symptomatic focal epilepsy not otherwise specified (71%)
      and five with West syndrome (21%). Of these 24 children, many had developmental
      problems (100%), behavioral problems (54%) or facial dysmorphisms (46%). We
      further identified five novel CNVs comprising four potential candidate genes for
      epilepsy: MYT1L, UNC5D, SCN4B, and NRXN3. Significance: The 11% yield in our
      hospital-based cohort underscores the importance of microarray analysis in
      diagnostic evaluation of children with epilepsy.

PMID- 29588954
TI  - Frequent sleep-related bitemporal focal seizures in transient epileptic amnesia
      syndrome: Evidence from ictal video-EEG.
AB  - Two patients who shared similar presenting clinical features of anterograde and
      retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA)
      underwent prolonged video electroencephalogram (VEEG) monitoring and were found
      to have sleep-activated epileptiform activity and frequent subclinical bitemporal
      seizures predominantly during sleep. Case 1 is a 59-year-old woman whose
      presenting complaint was memory impairment. Over 18 months, she had three
      distinct 8-h-long episodes of confusion and disorientation with persistent
      anterograde and retrograde autobiographical amnesia. VEEG recorded frequent
      interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures,
      also mostly during sleep. Case 2 is a 50-year-old woman with known focal epilepsy
      also presented with memory complaints. Over the course of 1 year, she had two
      discrete 2-h-long episodes of amnesia, with ongoing anterograde and retrograde
      autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and
      14 subclinical seizures during sleep and drowsiness. Memory impairment improved
      in both patients with successful treatment of their seizures. Although the
      etiology of accelerated long-term forgetting (ALF) and remote memory impairment
      (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest
      frequent sleep-related seizures may contribute, and they highlight the importance
      of video-EEG monitoring.

PMID- 29588955
TI  - Complex observation of scalp fast (40-150 Hz) oscillations in West syndrome and
      related disorders with structural brain pathology.
AB  - We investigated the relationship between the scalp distribution of fast (40-150
      Hz) oscillations (FOs) and epileptogenic lesions in West syndrome (WS) and
      related disorders. Subjects were 9 pediatric patients with surgically confirmed
      structural epileptogenic pathology (age at initial electroencephalogram [EEG]
      recording: mean 7.1 months, range 1-22 months). The diagnosis was WS in 7
      patients, Ohtahara syndrome in 1, and a transitional state from Ohtahara syndrome
      to WS in the other. In the scalp EEG data of these patients, we conservatively
      detected FOs, and then examined the distribution of FOs. In five patients, the
      scalp distribution of FOs was consistent and concordant with the lateralization
      of cerebral pathology. In another patient, FOs were consistently dominant over
      the healthy cerebral hemisphere, and the EEG was relatively low in amplitude over
      the pathological atrophic hemisphere. In the remaining 3 patients, the dominance
      of FOs was inconsistent and, in 2 of these patients, the epileptogenic hemisphere
      was reduced in volume, which may result from atrophy or hypoplasia. The
      correspondence between the scalp distribution of FOs and the epileptogenic lesion
      should be studied, taking the type of lesion into account. The factors affecting
      scalp FOs remain to be elucidated.

PMID- 29588956
TI  - High-frequency oscillations detected in ECoG recordings correlate with cavernous
      malformation and seizure-free outcome in a child with focal epilepsy: A case
      report.
AB  - Epilepsy associated with cavernous malformation (CM) often requires surgical
      resection of seizure focus to achieve seizure-free outcome. High-frequency
      oscillations (HFOs) in intracranial electroencephalogram (EEG) are reported as
      potential biomarkers of epileptogenic regions, but to our knowledge there are no
      data on the existence of HFOs in CM-caused epilepsy. Here we report our
      experience of the identification of the seizure focus in a 3-year-old pediatric
      patient with intractable epilepsy associated with CM. The electrocorticographic
      recordings were obtained from a 64-contact grid over 2 days in the epilepsy
      monitoring unit (EMU). The spatial distribution of HFOs and epileptic spikes were
      estimated from recording segments right after the electrode placement, during
      sleep and awake states separately. The HFO distribution showed consistency with
      the perilesional region; the location of spikes varied over days and did not
      correlate with the lesion. The HFO spatial distribution was more compact in sleep
      state and pinpointed the contacts sitting on the CM border. Following the
      resection of the CM and the hemosiderin ring, the patient became seizure-free.
      This is the first report describing HFOs in a pediatric patient with intractable
      epilepsy associated with CM and shows their potential in identifying the seizure
      focus.

PMID- 29588957
TI  - DRESS syndrome: A case of cross-reactivity with lacosamide?
AB  - A 42-year-old patient with epilepsy was admitted to the hospital for fever and
      generalized skin rash. He has known allergy to phenytoin. Valproate was started
      in 2012, but failed to control his seizure despite gradual increase in dosage.
      Phenobarbitone was added 16 days before admission and was stopped on admission.
      He was treated with beta-lactam antibiotics. The rash subsided gradually after
      the cessation of phenobarbitone. Lacosamide was subsequently added for seizure
      control. Unfortunately, he developed drug reaction with eosinophilia and systemic
      symptoms (DRESS) syndrome soon after introduction of lacosamide that required the
      use of systemic steroid for acute hepatitis. A cross-reactivity with lacosamide
      was suspected in view of the rapid onset of DRESS syndrome after the initial rash
      resolution and soon after the introduction of lacosamide. We postulated that the
      rapid onset of DRESS syndrome may be related to the aromatic ring that is in
      common among phenytoin, phenobarbitone, and lacosamide.

PMID- 29588959
TI  - PNES around the world: Where we are now and how we can close the diagnosis and
      treatment gaps-an ILAE PNES Task Force report.
AB  - An international consensus clinical practice statement issued in 2011 ranked
      psychogenic nonepileptic seizures (PNES) among the top three neuropsychiatric
      problems. An ILAE PNES Task Force was founded and initially charged with
      summarizing the current state of the art in terms of diagnosis and treatment,
      resulting in two publications. The first described different levels of diagnostic
      certainty. The second summarized current knowledge of management approaches. The
      present paper summarizes an international workshop of the ILAE PNES Task Force
      that focused on the current understanding and management of PNES around the
      world. We initially provide a knowledge update about the etiology, epidemiology,
      and prognosis of PNES-in adults and in special patient groups, such as children,
      older adults, and those with intellectual disability. We then explore clinical
      management pathways and obstacles to optimal care for this disorder around the
      world by focusing on a number of countries with different cultural backgrounds
      and at very different stages of social and economic development (United Kingdom,
      U.S.A., Zambia, Georgia, China, and Japan). Although evidence-based methods for
      the diagnosis and treatment of PNES have now been described, and much is known
      about the biopsychosocial underpinnings of this disorder, this paper describes
      gaps in care (not only in less developed countries) that result in patients with
      PNES not having adequate access to healthcare provisions. A range of challenges
      requiring solutions tailored to different healthcare systems emerges. Continued
      attention to PNES by the ILAE and other national and international neurologic,
      psychiatric, and health organizations, along with ongoing international
      collaboration, should ensure that patients with PNES do not lose out as
      healthcare services evolve around the world.

PMID- 29588960
TI  - The relationship between d-beta-hydroxybutyrate blood concentrations and seizure
      control in children treated with the ketogenic diet for medically intractable
      epilepsy.
AB  - Objective: The ketogenic diet (KD) is a proven treatment for drug-resistant (DR)
      seizures in children and adolescents. However, the relationship between seizure
      control and the most commonly measured metabolite of the diet, the ketone body d
      beta-hydroxybutyrate (D-BHB), is controversial. This study was performed to
      clarify the relationship because specific ketone bodies may be useful as
      biomarkers of diet efficacy. Methods: Families of children with DR seizures were
      approached for participation in this open-label, prospective study when they were
      referred for the KD at two western Canadian children's hospitals. Inclusion
      criteria included documentation of DR seizures without exclusion based on age,
      sex, seizure, or syndrome type. Patients were excluded if they were referred for
      treatment of a metabolic disorder independent of seizures. Seizures were
      quantified via parental report and standardized as seizure frequency per 28 days.
      Epilepsy syndromes were identified on the basis of the medical record. Blood D
      BHB was determined by tandem mass spectrometry. Results: A total of 23 patients
      were recruited from both sites. Data from five individuals were excluded because
      these seizures occurred in clusters, leaving 18 patients for the primary
      analysis. In the latter group, a clear positive correlation was present between
      measures of seizure frequency and D-BHB concentrations. However, this failed to
      reach statistical significance, likely because of the relatively small numbers.
      Significance: A trend clearly exists between seizure frequency and D-BHB levels,
      so we should not be dissuaded by the lack of statistical significance because it
      possibly results from methodological techniques, especially sample size. These
      results call for a larger prospective study in which seizure frequency is
      assessed at the point of care in a standardized fashion so as to determine
      whether D-BHB can be used as a reliable biomarker of KD efficacy.

PMID- 29588961
TI  - Automated long-term EEG analysis to localize the epileptogenic zone.
AB  - Objective: We investigated the performance of automatic spike detection and
      subsequent electroencephalogram (EEG) source imaging to localize the
      epileptogenic zone (EZ) from long-term EEG recorded during video-EEG monitoring.
      Methods: In 32 patients, spikes were automatically detected in the EEG and
      clustered according to their morphology. The two spike clusters with most single
      events in each patient were averaged and localized in the brain at the half
      rising time and peak of the spike using EEG source imaging. On the basis of the
      distance from the sources to the resection and the known patient outcome after
      surgery, the performance of the automated EEG analysis to localize the EZ was
      quantified. Results: In 28 out of the 32 patients, the automatically detected
      spike clusters corresponded with the reported interictal findings. The median
      distance to the resection in patients with Engel class I outcome was 6.5 and 15
      mm for spike cluster 1 and 27 and 26 mm for cluster 2, at the peak and the half
      rising time of the spike, respectively. Spike occurrence (cluster 1 vs. cluster
      2) and spike timing (peak vs. half-rising) significantly influenced the distance
      to the resection (p < 0.05). For patients with Engel class II, III, and IV
      outcomes, the median distance increased to 36 and 36 mm for cluster 1. Localizing
      spike cluster 1 at the peak resulted in a sensitivity of 70% and specificity of
      100%, positive prediction value (PPV) of 100%, and negative predictive value
      (NPV) of 53%. Including the results of spike cluster 2 led to an increased
      sensitivity of 79% NPV of 55% and diagnostic OR of 11.4, while the specificity
      dropped to 75% and the PPV to 90%. Significance: We showed that automated
      analysis of long-term EEG recordings results in a high sensitivity and
      specificity to localize the epileptogenic focus.

PMID- 29588963
TI  - Phenytoin as a last-resort treatment in SCN8A encephalopathy.
AB  - SCN8A encodes Nav1.6, one of the main voltage-gated sodium channel subunits in
      the brain, and SCN8A mutations lead to epileptic encephalopathy. Particular
      mutations render the mutant channel more susceptible to inhibition by phenytoin.
      Yet, the potentially severe side effects of phenytoin maintenance therapy,
      especially cognitive impairment, are undesirable in these already cognitively
      impaired patients. We describe a 5-year-old patient with SCN8A encephalopathy in
      whom phenytoin proved successful as emergency treatment to prevent clustering of
      seizures and status epilepticus, thus hospital stays. The ketogenic diet,
      levetiracetam, zonisamide, topiramate, and phenytoin maintenance therapy resulted
      in adverse reactions not previously documented in SCN8A encephalopathy.

PMID- 29588962
TI  - Functional variants in HCN4 and CACNA1H may contribute to genetic generalized
      epilepsy.
AB  - Objective: Genetic generalized epilepsy (GGE) encompasses seizure disorders
      characterized by spike-and-wave discharges (SWD) originating within thalamo
      cortical circuits. Hyperpolarization-activated (HCN) and T-type Ca2+ channels are
      key modulators of rhythmic activity in these brain regions. Here, we screened
      HCN4 and CACNA1H genes for potentially contributory variants and provide their
      functional analysis. Methods: Targeted gene sequencing was performed in 20
      unrelated familial cases with different subtypes of GGE, and the results
      confirmed in 230 ethnically matching controls. Selected variants in CACNA1H and
      HCN4 were functionally assessed in tsA201 cells and Xenopus laevis oocytes,
      respectively. Results: We discovered a novel CACNA1H (p.G1158S) variant in two
      affected members of a single family. One of them also carried an HCN4 (p.P1117L)
      variant inherited from the unaffected mother. In a separate family, an HCN4
      variant (p.E153G) was identified in one of several affected members. Voltage
      clamp analysis of CACNA1H (p.G1158S) revealed a small but significant gain-of
      function, including increased current density and a depolarizing shift of steady
      state inactivation. HCN4 p.P1117L and p.G153E both caused a hyperpolarizing shift
      in activation and reduced current amplitudes, resulting in a loss-of-function.
      Significance: Our results are consistent with a model suggesting cumulative
      contributions of subtle functional variations in ion channels to seizure
      susceptibility and GGE.

PMID- 29588964
TI  - Application of RNS in refractory epilepsy: Targeting insula.
AB  - Although responsive neurostimulation (RNS) is approved for treatment of resistant
      focal epilepsy in adults, little is known about response to treatment of specific
      cortical targets. We describe the experience of RNS targeting the insular lobe.
      We identified patients who had RNS implantation with at least one electrode
      within the insula between April 2014 and October 2015. We performed a
      retrospective review of preoperative clinical features, imaging,
      electrocardiogram (EEG), intraoperative electrocorticography (ECoG), and
      postoperative seizure outcome. Eight patients with at least 6 months of
      postimplant follow-up were identified. Ictal localization was inconclusive with
      MRI or scalp EEG findings. Intracranial EEG monitoring or intraoperative ECoG
      demonstrated clear ictal onsets and/or frequent interictal discharges in the
      insula. Four patients demonstrated overall 50-75% reduction in seizure frequency.
      Two patients did not show appreciable seizure improvement. One patient has
      experienced a 75% reduction of seizure frequency, and another is nearly seizure
      free postoperatively. There were no reported direct complications of insular RNS
      electrode placement or stimulation, though two patients had postoperative
      complications thought to be related to craniotomy (hydrocephalus and late
      infection). Our study suggests that insular RNS electrode placement in selected
      patients is relatively safe and that RNS treatment may benefit selected patients
      with insular epilepsy.

PMID- 29588965
TI  - Eucalyptus oil inhalation-induced seizure: A novel, underrecognized, preventable
      cause of acute symptomatic seizure.
AB  - Eucalyptus oil (EO) is an essential oil that is widely used across the globe as
      an over-the-counter remedy for common ailments. EO-induced seizure (EOIS) has not
      been recognized as an entity, and physicians rarely ask the history of exposure
      to eucalyptus oil when seeing a patient with first episode of seizure. Here we
      report 10 cases of EO inhalation-induced seizures seen over the past 2 years in
      three tertiary care hospitals. Eight patients had GTCS and two had CPS. We aim to
      raise awareness of seizures induced by exposure to eucalyptus oil.

PMID- 29588966
TI  - Pathogenic potential of antibodies to the GABAB receptor.
AB  - GABAB receptor (GABABR) autoantibodies have been detected in the serum of
      immunotherapy-responsive patients with autoimmune encephalitis. This study aimed
      to investigate the effect of immunoglobulin G (IgG) from a patient with GABABR
      antibodies on primary neuronal cultures and acute slices of entorhinal cortex.
      Primary hippocampal neuronal cultures were incubated with serum immunoglobulin
      from patients with GABABR or AMPA receptor (AMPAR) antibodies for up to 72 h to
      investigate their effect on receptor surface expression. Whole-cell patch-clamp
      recordings from layer III pyramidal cells of the medial entorhinal cortex were
      used to examine the effect on neuronal activity. GABABR surface expression was
      unaltered by incubation with GABABR antibodies. By contrast, after 24 h
      application of AMPAR antibodies, AMPARs were undetectable. However, acute
      application of GABABR IgG decreased both the duration of network UP states and
      the spike rate of pyramidal cells in the entorhinal cortex. GABABR antibodies do
      not appear to affect GABABRs by internalization but rather reduce excitability on
      the medial temporal lobe networks. This unusual mechanism of action may be
      exploited in rational drug development strategies.

PMID- 29588968
TI  - Announcing the new Epilepsia Open Prizes.

PMID- 29588970
TI  - Prevalence, risk factors, and neurobehavioral comorbidities of epilepsy in Kenyan
      children.
AB  - Objective: To investigate the prevalence, risk factors, clinical features, and
      neurobehavioral comorbidities of epilepsy and acute symptomatic seizures in
      school-aged children in Kilifi, Kenya. Methods: Randomly selected children (N =
      11,223) were screened for epilepsy and other neurodevelopmental disorders. Those
      who screened positive were invited for further clinical, electroencephalographic
      (EEG), and neuropsychological evaluations. Prevalence was measured by dividing
      cases by screened population, providing Agresti-Coull confidence intervals (CIs).
      Prevalence ratios were computed using log binomial regression, and odds ratios
      (ORs) were computed using logistic regression; both were implemented with
      generalized linear models. Attention-deficit hyperactivity disorder (ADHD),
      autism spectrum disorder (ASD), and other neurodevelopmental impairments were
      assessed in cases and controls. Results: Prevalence of lifetime epilepsy was 20.9
      per 1,000 (95% CI = 18.4-23.7), and that of active epilepsy was 11.5 per 1,000
      (95% CI = 9.7-13.6). Prevalence of acute symptomatic seizures was 68.8 per 1,000
      (95% CI = 64.2-73.6). Acute symptomatic seizures preceded a diagnosis of epilepsy
      in 8% of children. Of 98 children diagnosed with epilepsy, focal seizures were
      seen in 79%, abnormal EEG was seen in 39%, and 83% were not receiving
      antiepileptic drugs. Childhood absence epilepsy and Lennox-Gastaut epilepsy were
      the most easily identifiable epilepsy syndromes. Perinatal complications,
      previous hospitalization, geophagia, and snoring were risk factors for epilepsy.
      Family history of seizures, abnormal pregnancy, previous hospitalization, and
      snoring were risk factors for acute symptomatic seizures. Neurobehavioral
      comorbidities were present in 54% of subjects with lifetime epilepsy and in 3% of
      controls, with associations for individual comorbidities being statistically
      significant: ADHD (OR = 14.55, 95% CI = 7.54-28.06), ASD (OR = 36.83, 95% CI =
      7.97-170.14), and cognitive impairments (OR = 14.55, 95% CI = 3.52-60.14).
      Significance: The burden of seizure disorders in this area is higher than in
      locations in high-income countries, and can be reduced by preventing risk
      factors. A comprehensive management plan for neurobehavioral comorbidities of
      epilepsy should be incorporated into standard epilepsy care.

PMID- 29588969
TI  - Neurostimulation as a promising epilepsy therapy.
AB  - The revolution in theory, swift technological developments, and invention of new
      devices have driven tremendous progress in neurostimulation as a third-line
      treatment for epilepsy. Over the past decades, neurostimulation took its place in
      the field of epilepsy as an advanced treatment technique and opened up a new
      world. Numerous animal studies have proven the physical efficacy of stimulation
      of the brain and peripheral nerves. Based on this optimistic fundamental
      research, new advanced techniques are being explored in clinical practice. Over
      the past century, drawing on the benefits brought about by vagus nerve
      stimulation for the treatment of epilepsy, various new neurostimulation
      modalities have been developed to control seizures. Clinical studies including
      case reports, case series, and clinical trials have been booming in the past
      several years. This article gives a comprehensive review of most of these
      clinical studies. In addition to highlighting the advantages of neurostimulation
      for the treatment of epilepsy, concerns with this modality and future development
      directions are also discussed. The biggest advantage of neurostimulation over
      pharmacological treatments for epilepsy is the modulation of the epilepsy network
      by delivering stimuli at a specific target or the "hub." Conversely, however, a
      lack of knowledge of epilepsy networks and the mechanisms of neurostimulation may
      hinder further development. Therefore, theoretical research on the mechanism of
      epileptogenesis and epilepsy networks is needed in the future. Within the
      multiple modalities of neuromodulation, the final choice should be made after
      full discussion with a multidisciplinary team at a presurgical conference.
      Furthermore, the establishment of a neurostimulation system with standardized
      parameters and rigorous guidelines is another important issue. To achieve this
      goal, a worldwide collaboration of epilepsy centers is also suggested in the
      future.

PMID- 29588971
TI  - Personalized safety measures reduce the adverse event rate of long-term video
      EEG.
AB  - Objective: Safety in epilepsy monitoring units (EMUs) has become an increasing
      concern because adverse events occur in up to 10% of patients undergoing long
      term video EEG in EMUs. The aim of this study was to assess the effectiveness of
      a specific safety protocol in an EMU. Methods: We retrospectively assessed the
      adverse event rates in a group without (group 1, 84-month period, Innsbruck,
      Austria) and a group with (group 2, 33-month period, Salzburg, Austria)
      personalized safety measures utilizing a standardized protocol for long-term
      epilepsy monitoring in high-risk patients. Differences in adverse event rates
      during and after long-term video EEG between the two groups were calculated and
      compared. Results: In group 1, 44/507 (9%, 95% confidence interval [CI] 6.5
      11.5%) patients experienced 53 adverse events: 20/507 (4%, 95% CI 2.6-6.0%)
      patients had psychiatric events, 15/507 (3%, 95% CI 1.8-4.8%) patients sustained
      a total of 19 injuries during seizures, and 10/507 (2%, 95% CI 1.1-3.6%) patients
      had 13 episodes of status epilepticus; one adverse event was treatment-related
      (valproic acid-induced encephalopathy; 1/507, 0.2%, 95% CI 0.0-1.1%). By using
      the new safety protocol in group 2, the adverse event rate was only 5% (95% CI
      3.4-7.6%; 30 adverse events in 26/491; 45% reduction; p = 0.036), in contrast.
      These events included 13 psychiatric complications in 13/491 (2%, 95% CI 1.6
      4.5%, p = 0.252) patients, 12 seizure-related injuries in 9/491 (2%, 95% CI 1.0
      3.4%, p = 0.250) patients, and 5 episodes of status epilepticus in 4/491 (1%, 95%
      CI 0.3-2.1%, p = 0.120) patients. Significance: Implementation of personalized
      safety measures in high-risk patients resulted in a clinically relevant reduction
      of adverse events in the EMU. Safety protocols are a valid tool to reduce the
      occurrence of adverse events in EMUs.

PMID- 29588972
TI  - Safety and tolerability of lacosamide monotherapy in the elderly: A subgroup
      analysis from lacosamide trials in diabetic neuropathic pain.
AB  - Objective: To assess the safety profile of lacosamide monotherapy in elderly
      (>=65 years) subjects with diabetic neuropathic pain (DNP). Methods: Of 1,863 DNP
      subjects in double-blind, randomized, placebo-controlled trials of lacosamide
      monotherapy (NCT00861445, NCT00235469, NCT00238524, NCT00135109, NCT00350103),
      502 were elderly. Safety data from elderly subjects were compared with that of
      younger subjects (<65 years) within these DNP trials. It should be noted that
      lacosamide is approved for the treatment of focal (partial-onset) seizures; it is
      not approved/recommended for the treatment of DNP. Results: Overall,
      cardiovascular diseases were prevalent in the DNP population, as was the use of
      cardiac, blood pressure, diabetes, and cholesterol-lowering medications among
      both young and elderly subjects. The most frequently reported adverse events
      (AEs) for lacosamide monotherapy (200, 400, and 600 mg/day combined) in elderly
      versus younger subjects were dizziness (16.2% vs. 13.2%), nausea (10.0% vs.
      9.4%), and headache (8.0% vs. 8.7%). Incidences of cardiac disorder AEs were
      higher in elderly versus younger subjects receiving placebo (6.2% vs. 3.9%),
      lacosamide 200 (4.8% vs. 3.3%), lacosamide 400 (7.0% vs. 4.1%), and lacosamide
      600 mg/day (7.7% vs. 4.0%). Discontinuation rates because of any AE in the
      elderly versus younger subjects were similar for placebo (8.8% vs. 7.0%) and
      lacosamide 200 mg/day (9.6% vs. 11.9%) and higher for lacosamide 400 (25.1% vs.
      10.8%) and lacosamide 600 mg/day (52.7% vs. 28.3%). Significance: Lacosamide
      monotherapy was well tolerated in elderly subjects with DNP, with an overall AE
      profile consistent with that reported in epilepsy trials.

PMID- 29588973
TI  - Multimodal, automated detection of nocturnal motor seizures at home: Is a
      reliable seizure detector feasible?
AB  - Objective: Automated seizure detection and alarming could improve quality of life
      and potentially prevent sudden, unexpected death in patients with severe
      epilepsy. As currently available systems focus on tonic-clonic seizures, we want
      to detect a broader range of seizure types, including tonic, hypermotor, and
      clusters of seizures. Methods: In this multicenter, prospective cohort study, the
      nonelectroencephalographic (non-EEG) signals heart rate and accelerometry were
      measured during the night in patients undergoing a diagnostic video-EEG
      examination. Based on clinical video-EEG data, seizures were classified and
      categorized as clinically urgent or not. Seizures included for analysis were
      tonic, tonic-clonic, hypermotor, and clusters of short myoclonic/tonic seizures.
      Features reflecting physiological changes in heart rate and movement were
      extracted. Detection algorithms were developed based on stepwise fulfillment of
      conditions during increases in either feature. A training set was used for
      development of algorithms, and an independent test set was used for assessing
      performance. Results: Ninety-five patients were included, but due to sensor
      failures, data from only 43 (of whom 23 patients had 86 seizures, representing
      402 h of data) could be used for analysis. The algorithms yield acceptable
      sensitivities, especially for clinically urgent seizures (sensitivity = 71-87%),
      but produce high false alarm rates (2.3-5.7 per night, positive predictive value
      = 25-43%). There was a large variation in the number of false alarms per patient.
      Significance: It seems feasible to develop a detector with high sensitivity, but
      false alarm rates are too high for use in clinical practice. For further
      optimization, personalization of algorithms may be necessary.

PMID- 29588974
TI  - Seizures, electroencephalographic abnormalities, and outcome of ischemic stroke
      patients.
AB  - Objective: Seizures and electroencephalographic (EEG) abnormalities have been
      associated with unfavorable stroke functional outcome. However, this association
      may depend on clinical and imaging stroke severity. We set out to analyze whether
      epileptic seizures and early EEG abnormalities are predictors of stroke outcome
      after adjustment for age and clinical/imaging infarct severity. Methods: A
      prospective study was made on consecutive and previously independent acute stroke
      patients with a National Institutes of Health Stroke Scale (NIHSS) score >= 4 on
      admission and an acute anterior circulation ischemic lesion on brain imaging. All
      patients underwent standardized clinical and diagnostic assessment during
      admission and after discharge, and were followed for 12 months. Video-EEG (<60
      min) was performed in the first 72 h. The Alberta Stroke Program Early CT Score
      quantified middle cerebral artery infarct size. The outcomes in this study were
      an unfavorable functional outcome (modified Rankin Scale [mRS] >= 3) and death
      (mRS = 6) at discharge and 12 months after stroke. Results: Unfavorable outcome
      at discharge was independently associated with NIHSS score (p = 0.001), EEG
      background activity slowing (p < 0.001), and asymmetry (p < 0.001). Unfavorable
      outcome 1 year after stroke was independently associated with age (p = 0.001),
      NIHSS score (p < 0.001), remote symptomatic seizures (p = 0.046), EEG background
      activity slowing (p < 0.001), and asymmetry (p < 0.001). Death in the first year
      after stroke was independently associated with age (p = 0.028), NIHSS score (p =
      0.001), acute symptomatic seizures (p = 0.015), and EEG suppression (p = 0.019).
      Significance: Acute symptomatic seizures were independent predictors of vital
      outcome and remote symptomatic seizures of functional outcome in the first year
      after stroke. Therefore, their recognition and prevention strategies may be
      clinically relevant. Early EEG abnormalities were independent predictors and
      comparable to age and early clinical/imaging infarct severity in stroke
      functional outcome discrimination, reflecting the concept that EEG is a sensitive
      and robust method in the functional assessment of the brain.

PMID- 29588975
TI  - A comparison of waiting times for assessment and epilepsy surgery between a
      Canadian and a Mexican referral center.
AB  - Objective: To provide a comprehensive transnational overview of wait times for
      epilepsy surgery in Canada and Mexico. Methods: We reviewed all cases referred
      for epilepsy surgery between 2007 and 2015 at the Saskatchewan Epilepsy Program
      Royal University Hospital (SEP) (n = 70; Saskatoon, Canada) and the National
      Institute of Neurology and Neurosurgery (NINN) (n = 76; Mexico City, Mexico) and
      compared wait times, calculated as the time from diagnosis of epilepsy on
      assessment at an epilepsy center to epilepsy surgery. Results: Mean wait times
      were similar across centers. Mean patient age was 37.4 +/- 9 years (NINN) and
      36.7 +/- 13.2 years (SEP). The mean time from epilepsy diagnosis to referral was
      18.9 (NINN) and 16.9 years (SEP), p = 0.30; first consult with the
      epileptologist, 19.7 (NINN) and 17.4 years (p = 0.23); neuropsychology consult,
      21.4 (NINN) and 17.9 years (SEP); video electroencephalogram (video-EEG)
      telemetry, 21.1 (NINN) and 18.6 months (SEP); initial neurosurgical consult, 21.9
      (NINN) and 19.1 years (SEP) (p = 0.35); and epilepsy surgery, 19.7 (NINN) and
      19.6 years (SEP) (p = 0.29). Significance: This is the first study to compare
      wait times between Canada and Mexico. Despite disparity in their health delivery
      systems and financial resources, surgical wait times appeared to be protracted in
      both nations, confirming that delayed treatment is a universal problem that
      requires collaborative scrutiny.

PMID- 29588976
TI  - Incidence of seizure exacerbation and seizures reported as adverse events during
      adjunctive treatment with eslicarbazepine acetate: A pooled analysis of three
      Phase III controlled trials.
AB  - Objective: To investigate whether adjunctive eslicarbazepine acetate (ESL) could
      lead to exacerbation of seizures in some patients. Methods: Post-hoc analysis of
      data pooled from three Phase III trials of adjunctive ESL (studies 301, 302, and
      304) for refractory partial-onset seizures (POS). Following an 8-week baseline
      period, patients were randomized to receive placebo or ESL 400, 800, or 1,200 mg
      once daily (2-week titration, 12-week maintenance, 2-4 week tapering-off
      periods). Patient seizure diary data and seizure treatment-emergent adverse event
      (TEAE) reports were pooled for analysis. Results: The modified intent-to-treat
      and safety populations comprised 1,410 patients and 1,447 patients, respectively.
      Titration period: Compared with placebo (32/21%), significantly smaller
      proportions of patients taking ESL 800 mg (20/15%) and 1,200 mg (22/12%) had a
      >=25/>=50% increase in standardized seizure frequency (SSF) from baseline; there
      was no significant difference between placebo and ESL 400 mg. Maintenance period:
      Compared with placebo (20%), significantly smaller proportions of patients taking
      ESL (400 mg, 12%; 800 mg, 12%; 1,200 mg, 14%) had an increase in SSF >=25%. When
      evaluating >=50% increases in SSF, only ESL 800 mg (7%) was significantly
      different from placebo (12%). Some patients had no secondarily generalized tonic
      clonic (sGTC) seizures during baseline but had >=1 sGTC seizure during
      maintenance treatment (placebo, 11%; ESL 400 mg, 5%; 800 mg, 10%; 1,200 mg, 5%).
      Fewer patients had a >=25% increase in sGTC seizure frequency with ESL (400 mg,
      11%; 800 mg, 9%; 1,200 mg, 14%) versus placebo (19%). The incidence of seizures
      reported as TEAEs was low in all treatment groups; incidences were generally
      lower with ESL versus placebo. Tapering-off period: Similar proportions of
      patients taking ESL and placebo had a >=25/>=50% increase in SSF. Seizure TEAE
      incidence was numerically higher with ESL versus placebo. Significance: Treatment
      with adjunctive ESL does not appear to aggravate POS or sGTC seizures.

PMID- 29588977
TI  - Simultaneous occurrence of nonepileptic and epileptic seizures during a single
      period of in-patient video-electroencephalographic monitoring.
AB  - Epilepsy and psychogenic nonepileptic seizures (PNES) can coexist and may present
      in two forms: sequential and simultaneous. In sequential presentations, epileptic
      seizures (ES) are treated and PNES emerge later. Simultaneous recording of ES and
      PNES by video-electroencephalogram (vEEG) is less well described. We
      retrospectively reviewed all patients diagnosed with PNES by vEEG following
      standard seizure induction practices over a 21-month period. Within this cohort,
      we established the prevalence of coexisting epilepsy using clinical and
      electrographic data acquired from our epilepsy-specific patient record. We
      identified patients with simultaneous PNES and ES recorded during a single vEEG
      admission, establishing the frequency and emergent timing of each type. Of our
      262 monitored patients, 59 were diagnosed with PNES. Nineteen of the patients
      with PNES had coexisting epilepsy (prevalence rate of 7.3% or 32% of those with
      PNES). Sixteen patients had PNES and ES recorded during the same admission, and
      the remaining three patients had sequential PNES following successful treatment
      of ES. PNES occurred earlier (mean, within 1.21 days), with ES occurring later
      (mean, within 4.86 days). The simultaneous occurrence of PNES and ES recorded
      during a single admission is more common than previously reported. Identifying
      this group of patients may require a significantly longer period of vEEG
      monitoring and a detailed analysis of each individual's historical seizure
      events.

PMID- 29588978
TI  - Topography of generalized periodic epileptiform discharges in postanoxic
      nonconvulsive status epilepticus.
AB  - We studied slow (<=2.5 Hz) nonevolving generalized periodic epileptiform
      discharges (GPEDs) in the electroencephalogram (EEG) of comatose patients after
      cardiac arrest (CA) in search of evidence that could assist early diagnosis of
      possible hypoxic nonconvulsive status epilepticus (NCSE) and its differentiation
      from terminal brain anoxia (BA), which can present with a similar EEG pattern. We
      investigated the topography of the GPEDs in the first post-CA EEGs of 13
      patients, using voltage-mapping, and compared findings between two patients with
      NCSE and GPEDs > 2.5 Hz (group 1), and 11 with GPEDs <= 2 Hz, of whom six had
      possible NCSE (group 2) and five had terminal BA (group 3). Voltage mapping
      showed frontal maximum for the negative phase of the GPEDs in all patients of
      groups 1 and 2, but not in any of the patients of group 3, who invariably showed
      maximization of the negative phase posteriorly. Morphology, amplitude, and
      duration of the GPEDs varied across the groups, without distinctive features for
      possible NCSE. These findings provide evidence that, in hypoxic coma after CA
      with slow GPEDs, anterior topography of the maximum GPED negativity on voltage
      mapping may be a distinctive biomarker for possible NCSE contributing to the
      coma.

PMID- 29588979
TI  - Claustrum hyperintensities: A potential clue to autoimmune epilepsy.
AB  - In a cohort of 34 patients with autoimmune limbic encephalitis and/or epilepsy,
      we identified 4 patients exhibiting claustrum fluid-attenuated inversion recovery
      (FLAIR) hyperintensities. All 4 patients presented with explosive onset of
      seizures and developed medically intractable epilepsy, and 2 exhibited a marked
      response to immunotherapy. Associated features included cognitive and behavioral
      disturbances (4/4), cerebrospinal fluid (CSF) lymphocytic pleocytosis (3/4), and
      a neural autoantibody (2/4). Electroencephalogram (EEG) features consisted of
      slow wave activity and epileptiform discharges in frontal and parasagittal
      regions, where ictal patterns were captured in 1 patient. In 1 patient,
      magnetoencephalographic source imaging of interictal spikes revealed dipole
      sources in anterior insular or subinsular localizations, mirroring claustrum
      FLAIR hyperintensities, which developed after a short lag from presentation and
      resolved in all but 1 patient. These MRI abnormalities were isolated (2/4) or
      associated with mesial temporal hyperintensities (2/4). Claustrum FLAIR
      hyperintensities may be a useful MRI marker of autoimmune epilepsy.

PMID- 29588980
TI  - Novel bandlike signal abnormality suggestive of heterotopia in patient with a
      KCNQ1 frameshift mutation.
AB  - Malformations of cortical development are associated with epilepsy and cognitive
      dysfunction, and can occur in patients with SCN1A ion channel mutations. We
      report a novel and subtle bandlike subcortical heterotopia on integrated positron
      emission tomography-magnetic resonance imaging ( PET-MRI) in a patient with
      treatment-resistant epilepsy due to a de novo KCNQ1 frameshift mutation. Our case
      highlights the potential for other channel mutations to cause both epilepsy and
      cortical malformations. Further scrutiny of high contrast resolution MRI studies
      is warranted for patients with KCNQ1 and other epilepsy genes to further define
      their extended phenotype.

PMID- 29588983
TI  - Ketogenic diet for treatment of intractable epilepsy in adults: A meta-analysis
      of observational studies.
AB  - The ketogenic diet (KD) is an effective treatment for children with drug
      resistant epilepsy and has been widely used in young children. Adult patients
      with intractable epilepsy would also benefit from this dietary treatment.
      However, only a few studies have been published, and the use of the KD in
      intractable epilepsy in adults has been limited. This meta-analysis summarized
      the findings of the relevant published studies to identify the efficacy of the KD
      for the treatment of intractable epilepsy in adults. In this meta-analysis,
      PubMed, Embase, and Cochrane Library were used for searching studies concerning
      the effects of the KD and its major subtypes with intractable epilepsy in adults
      published up to January 10, 2017. The primary outcomes were seizure freedom,
      seizure reduction by 50% or more, and seizure reduction by <50%. The quality of
      the methodology of the observational studies was reviewed by using the Newcastle
      Ottawa Scale. We identified 402 articles, of which, 16 studies including 338
      patients met the inclusion criteria. The results of the meta-analysis showed that
      the combined efficacy rates of all the symptoms of seizure freedom, seizure
      reduction by 50% or more, and seizure reduction below 50% in adults with
      intractable epilepsy were 13%, 53%, and 27%, respectively. The adverse reactions
      of the KD were mild, whereas low glycemic index diet (LGID) and low-dose fish oil
      diet (LFOD) may have fewer side effects. Weight loss, high level of low-density
      lipoprotein, and elevated total cholesterol were most frequent. The meta-analysis
      indicates that the KD for refractory epilepsy in adults is a well-tolerated
      treatment and that its side effects are acceptable, which show that the KD is a
      promising treatment in adult intractable epilepsy. Further research is needed to
      assess which type of diet or ratio is more effective in the KD treatment.

PMID- 29588984
TI  - Effect of neurostimulation on cognition and mood in refractory epilepsy.
AB  - Epilepsy is a common, debilitating neurological disorder characterized by
      recurrent seizures. Mood disorders and cognitive deficits are common
      comorbidities in epilepsy that, like seizures, profoundly influence quality of
      life and can be difficult to treat. For patients with refractory epilepsy who are
      not candidates for resection, neurostimulation, the electrical modulation of
      epileptogenic brain tissue, is an emerging treatment alternative. Several forms
      of neurostimulation are currently available, and therapy selection hinges on
      relative efficacy for seizure control and amelioration of neuropsychiatric
      comorbidities. Here, we review the current evidence for how invasive and
      noninvasive neurostimulation therapies affect mood and cognition in persons with
      epilepsy. Invasive therapies include vagus nerve stimulation (VNS), deep brain
      stimulation (DBS), and responsive neurostimulation (RNS). Noninvasive therapies
      include trigeminal nerve stimulation (TNS), repetitive transcranial magnetic
      stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall,
      current evidence supports stable cognition and mood with all neurostimulation
      therapies, although there is some evidence that cognition and mood may improve
      with invasive forms of neurostimulation. More research is required to optimize
      the effects of neurostimulation for improvements in cognition and mood.

PMID- 29588985
TI  - Ketogenic parenteral nutrition in 17 pediatric patients with epilepsy.
AB  - Objective: Ketogenic parenteral nutrition (kPN) is indicated when enteral intake
      is temporarily limited or impossible, but evidence-based prescriptions are
      lacking. Objective was to evaluate the efficacy and safety of kPN in children
      with epileptic encephalopathies using a new computer-based algorithm for accurate
      component calculating. Methods: Children with epilepsy receiving kPN were
      included. A computer-based algorithm was established on the basis of guidelines
      of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
      (ESPGHAN): fat intake not exceeding 4 g/kg/day, age-adequate supply of protein,
      electrolytes, vitamins, and trace elements, but reduced carbohydrates. Primary
      outcome was successfully reaching relevant ketosis, defined as beta
      hydroxybutyrate plasma level of >= 2 mmol/L. Efficacy was defined as seizure
      reduction >=50% in de novo kPN and maintenance of response in children already on
      a ketogenic diet (KD). Safety was assessed by adverse effects, laboratory
      findings, and the appropriateness of nutritional intake. Results: Seventeen
      children (median 1.84 years) were studied, of which 76% (13/17) were already on
      an oral ketogenic diet. Indications for kPN were surgery, status epilepticus,
      vomiting, food refusal, and introduction of enteral feeding in neonates. The
      parenteral fat/nonfat ratio was mean 0.9 (+/-0.3; range 0.6-1.5). Relevant
      ketosis was reached in 10 children (median 2.9 mmol/L), but not in 7 (median =
      1.4 mmol/L). In de novo kPN, significant response was observed in 50% (2/4); in
      patients previously responding to the KD (77%, 10/13), response was maintained. A
      significant correlation between the degree of ketosis and seizure reduction
      (correlation coefficient = 0.691; p = .002) was observed. Only mild and transient
      adverse events occurred during kPN. Significance: KPN with fat intake of 3.5-4.0
      g/kg/day was safe and effective. KPN was tailored according to guidelines and
      individual nutritional needs. In nearly half of the patients, ketosis was lower
      than during oral KD. Despite this, seizures remained controlled.

PMID- 29588986
TI  - Young people with epilepsy have an increased risk of eating disorder and poor
      quality diet.
AB  - Objective: To investigate whether adolescents with epilepsy are at increased risk
      of having self-reported eating disorder symptoms and poor quality diet compared
      to young people from the general population. Methods: We used data from the
      Health Profile for Children and Youth in Akershus Study, a cross-sectional
      population-based study based on a voluntary self-reported questionnaire. There
      were 19,995 participants (response rate 85%) aged 13-19 years; 247 (1.2%)
      reported a lifetime diagnosis of epilepsy. Odds ratios (OR) and 95% confidence
      intervals (CI) for eating disorders, unhealthy diet, dieting, satisfaction with
      looks, and participation in sports were estimated by using a logistic regression
      model. All estimates were adjusted for single parents and poor family economy.
      Results: Children and adolescents with epilepsy had more eating disorders than
      their peers (OR 1.8, CI 1.0-3.0, p = 0.03). They were less satisfied with their
      own appearance (OR 0.7, CI 0.5-0.9, p = 0.02), and they eat more unhealthily (OR
      1.7, CI 1.3-2.2, p = 0.001). Males with epilepsy were more likely to have been
      dieting (OR 3.1, CI 1.2-7.9, p = 0.02) and less satisfied with their own
      appearance (OR 0.4, CI 0.3-0.7, p < 0.001). Females with epilepsy were more
      likely to eat unhealthily (OR 1.7, CI 1.1-2.5, p = 0.01). Significance:
      Adolescents with epilepsy are at increased risk of having eating disorder
      symptoms. They eat less healthily and are less satisfied with their looks. Health
      workers should be aware of this and bring diet and lifestyle into the dialogue
      with young people with epilepsy.

PMID- 29588987
TI  - Single-item measure for assessing quality of life in children with drug-resistant
      epilepsy.
AB  - Objective: The current study investigated the psychometric properties of a single
      item quality of life (QOL) measure, the Global Quality of Life in Childhood
      Epilepsy question (G-QOLCE), in children with drug-resistant epilepsy. Method:
      Data came from the Impact of Pediatric Epilepsy Surgery on Health-Related Quality
      of Life Study (PESQOL), a multicenter prospective cohort study (n = 118) with
      observations collected at baseline and at 6 months of follow-up on children aged
      4-18 years. QOL was measured with the QOLCE-76 and KIDSCREEN-27. The G-QOLCE was
      an overall QOL question derived from the QOLCE-76. Construct validity and
      reliability were assessed with Spearman's correlation and intraclass correlation
      coefficient (ICC). Responsiveness was examined through distribution-based and
      anchor-based methods. Results: The G-QOLCE showed moderate (r >= 0.30) to strong
      (r >= 0.50) correlations with composite scores, and most subscales of the QOLCE
      76 and KIDSCREEN-27 at baseline and 6-month follow-up. The G-QOLCE had moderate
      test-retest reliability (ICC range: 0.49-0.72) and was able to detect clinically
      important change in patients' QOL (standardized response mean: 0.38; probability
      of change: 0.65; Guyatt's responsiveness statistics: 0.62 and 0.78). Caregiver
      anxiety and family functioning contributed most strongly to G-QOLCE scores over
      time. Significance: Results offer promising preliminary evidence regarding the
      validity, reliability, and responsiveness of the proposed single-item QOL
      measure. The G-QOLCE is a potentially useful tool that can be feasibly
      administered in a busy clinical setting to evaluate clinical status and impact of
      treatment outcomes in pediatric epilepsy.

PMID- 29588988
TI  - Repetitive transcranial magnetic stimulation for the treatment of drug-resistant
      epilepsy: A systematic review and individual participant data meta-analysis of
      real-world evidence.
AB  - Objective: To perform a systematic review and meta-analysis of real-world
      evidence for the use of low-frequency repetitive transcranial magnetic
      stimulation (rTMS) in the treatment of drug-resistant epilepsy. Methods: We
      systematically searched PubMed, Scopus, Medline, and clinicaltrials.gov for all
      relevant articles. Relevant patient and stimulation predictors as well as seizure
      outcomes were assessed. For studies with and without individual participant data
      (IPD), the primary outcomes were the rate of "favorable response" (reduction in
      seizure frequency >=50%) and pooled event rate of mean reduction in seizure
      frequency, respectively. Outcomes were assessed with comparative statistics and
      random-effects meta-analysis models. Results: Of 3,477 identified articles, 12
      met eligibility and were included in this review. We were able to obtain IPD for
      5 articles constituting 34 participants. Univariate analysis on IPD identified
      greater favorable response event rates between participants with temporal seizure
      focus versus extratemporal (50% vs. 14%, p = 0.045) and between participants who
      were stimulated with a figure-8 coil versus other types (47% vs. 0%, p = 0.01).
      We also performed study-level meta-analysis on the remaining 7 studies without
      IPD, which included 212 participants. The pooled mean event rate of 50% seizure
      reduction using low-frequency rTMS was 30% (95% confidence interval [CI] 12-57%).
      Sensitivity analysis revealed that studies with a mean age <=21 years and studies
      using targeted stimulation had the highest seizure reduction rates compared to
      studies with a mean age >21 years (69% vs. 18%) and not using a targeted
      stimulation (47% vs. 14-20%). Moreover, we identified high interstudy
      heterogeneity, moderate study bias, and high publication bias. Significance: Real
      world evidence suggests that low-frequency rTMS using a figure-8 coil may be an
      effective therapy for the treatment of drug-resistant epilepsy in pediatric
      patients. This meta-analysis can inform the design and expedite recruitment of a
      subsequent randomized clinical trial.

PMID- 29588989
TI  - Psychogenic non-epileptic seizures among patients with functional neurological
      disorder: A case series from a Tanzanian referral hospital and literature review.
AB  - Objective: Functional neurological disorders (FNDs) and psychogenic nonepileptic
      seizures (PNES) are likely as common in Sub-Saharan Africa (SSA) as in the rest
      of the world, but there is a dearth of literature on the epidemiology and
      clinical presentation of these disorders in Africa. The purpose of this paper is
      to describe a case series of FNDs presenting to a referral hospital in SSA. In
      addition, we review the existing literature on FNDs in Africa. Methods: A
      hospital-based retrospective cross-sectional study was conducted to determine the
      prevalence, epidemiology, and clinical phenotype of FNDs and PNES in a referral
      hospital in Northern Tanzania over a 6-year period (2007-2013). Results: Of 2,040
      patients presenting with neurological complaints, 44 (2.2%) were diagnosed with
      FNDs. Half (n = 22) had the clinical presentation of PNES. Age of presentation
      for FNDs and PNES peaked in the teen years 12-19 (n = 21 48%; and n = 14, 63%,
      respectively), and the majority were female (n = 30, 68%; and n = 14, 63%,
      respectively). The majority presented acutely with short-lived and self-limiting
      symptoms (only 2 recurrent cases). Literature review revealed multiple reports of
      "mass hysteria" in SSA often meeting the clinical criteria of epidemic FNDs.
      Significance: FNDs and PNES occur in Africa with age and gender distribution
      comparable to that found elsewhere. Although the percentage of FND cases overall
      was relatively low (2.2%), it is likely to be an underestimate because not all
      cases were recorded, and cases may be appropriately managed locally before
      patients are referred to a hospital. PNES was the most common phenotype of FNDs
      reported, and the African phenotype may be short-lived and self-limiting rather
      than chronic and recurrent, as reported elsewhere in the world. PNES
      presentations may also occur in clusters, which may have cultural significance in
      Africa. FNDs in Africa appear to be underreported, particularly over the last 30
      years.

PMID- 29588990
TI  - Time to push the age limit: Epilepsy surgery in patients 60 years or older.
AB  - Objective: To summarize the existing literature on resective epilepsy surgery
      (RES) in older adults (>=60 years old) and examine seizure and neuropsychological
      outcomes in a single-center large cohort of older adults undergoing RES and their
      comparison to a consecutive, younger (25- to45-year-old) adult population who
      underwent RES in routine clinical practice. Methods: First, a comprehensive
      literature review was performed. Then, we identified older adults who underwent
      RES at our center (2000-2015). Outcome analysis was performed on patients who had
      >=1 year of clinical follow-up. A younger cohort of patients who underwent RES
      during the same period was selected for comparison. The 2 groups were compared
      with respect to demographic and disease variables as well as key clinical
      outcomes. Results: Seizure outcomes on 58 older patients were reported in
      existing literature; 72% achieved Engel class I outcome >=1 year postoperatively.
      Sixty-four older adults underwent RES at our center, accounting for 2.8% of all
      RES during the study period. A total of 51 older adults (Mage = 65) among them
      had >=1-year clinical follow-up; 80% achieved Engel I outcome after a mean follow
      up of 3.2 years. This was comparable to the 68% Engel class I outcome among 50
      consecutive younger adults, despite later age of onset, longer epilepsy duration,
      and more comorbidities (all p < 0.001) among older adults. The majority (86%) of
      older adults were referred to our center after years of suffering from drug
      resistant epilepsy. There were no group differences in surgical complications.
      However, 1 older adult passed away post-RES. There was no difference in post-RES
      neuropsychological outcomes compared to younger adults, except significantly
      higher number of older adults showed a decline in confrontational naming.
      Significance: RES in well-selected older adults is a safe and effective therapy,
      and advanced age should not preclude consideration of surgical therapy in older
      adults with pharmacoresistant epilepsy.

PMID- 29588991
TI  - Early-onset epileptic encephalopathy and severe developmental delay in an
      association with de novo double mutations in NF1 and MAGEL2.
AB  - Advance in the exome-wide sequencing analysis contributes to identifying hundreds
      of genes that are associated with early-onset epileptic encephalopathy and
      neurodevelopmental disorders. On the basis of massive sequencing data, functional
      interactions among different genes are suggested to explain the common molecular
      pathway underlying the pathogenic process of these disorders. However, the
      relevance of such interactions with the phenotypic severity or variety in an
      affected individual remains elusive. In this report, we present a 45-year-old
      woman with neurofibromatosis type 1 (NF1), infantile-onset epileptic
      encephalopathy, and severe developmental delay. Whole-exome sequencing identified
      de novo pathogenic mutations in NF1 and the Schaaf-Yang syndrome-associated gene,
      MAGEL2. Literature-curated interaction data predicted that NF1 and MAGEL2
      proteins were closely connected in this network via their common interacting
      proteins. Direct conversion of fibroblasts into neurons in vitro showed that
      neuronal cells from 9 patients with NF1 expressed significantly lower levels of
      MAGEL2 (54%, p = 0.0047) than those from healthy individuals. These data provide
      the first evidence that pathogenic mutations of NF1 deregulate the expression of
      other neurodevelopmental disease-associated genes. De novo mutations in multiple
      genes may lead to severe developmental phenotypes through their cumulative
      effects or synergistic interactions.

PMID- 29588992
TI  - Are doses of lamotrigine or levetiracetam adjusted during pregnancy?
AB  - Subtherapeutic levels of lamotrigine and levetiracetam are more likely to occur
      during pregnancy owing to the effect of pregnancy on their pharmacokinetics. This
      can lead to suboptimal control of epilepsy, and guidelines recommend proactive
      dose adjustment in the second and third trimesters alongside therapeutic drug
      monitoring (TDM). This retrospective cohort study using administrative databases
      aimed to investigate whether prescribers adjust the dose of lamotrigine or
      levetiracetam during and after pregnancy and whether TDM is used to manage dose
      adjustment. In 460 individual pregnancies, 232 women (61.4%) had their
      lamotrigine dose increased in the second and third trimesters and 44 women
      (53.7%) had their levetiracetam dose increased. Only 57 women (12.4%) had any
      TDM. The dose was not always decreased postpartum, and 157 women (56.9% of those
      who had escalated doses during pregnancy) had dose reduced following birth.
      Between 2012 and 2015, 29 women had an epilepsy-coded hospital discharge during
      pregnancy and were more likely to have had their dose of lamotrigine or
      levetiracetam increased. Overall, doses of lamotrigine and levetiracetam were not
      increased during pregnancy in 40% of the study population, dose changes were not
      often guided by TDM, and doses were not always reduced postpartum.

PMID- 29588993
TI  - Common terms for rare epilepsies: Synonyms, associated terms, and links to
      structured vocabularies.
AB  - Identifying individuals with rare epilepsy syndromes in electronic data sources
      is difficult, in part because of missing codes in the International
      Classification of Diseases (ICD) system. Our objectives were the following: (1)
      to describe the representation of rare epilepsies in other medical vocabularies,
      to identify gaps; and (2) to compile synonyms and associated terms for rare
      epilepsies, to facilitate text and natural language processing tools for cohort
      identification and population-based surveillance. We describe the representation
      of 33 epilepsies in 3 vocabularies: Orphanet, SNOMED-CT, and UMLS-Metathesaurus.
      We compiled terms via 2 surveys, correspondence with parent advocates, and review
      of web resources and standard vocabularies. UMLS-Metathesaurus had entries for
      all 33 epilepsies, Orphanet 32, and SNOMED-CT 25. The vocabularies had
      redundancies and missing phenotypes. Emerging epilepsies (SCN2A-, SCN8A-, KCNQ2-,
      SLC13A5-, and SYNGAP-related epilepsies) were underrepresented. Survey and
      correspondence respondents included 160 providers, 375 caregivers, and 11
      advocacy group leaders. Each epilepsy syndrome had a median of 15 (range 6-28)
      synonyms. Nineteen had associated terms, with a median of 4 (range 1-41). We
      conclude that medical vocabularies should fill gaps in representation of rare
      epilepsies to improve their value for epilepsy research. We encourage epilepsy
      researchers to use this resource to develop tools to identify individuals with
      rare epilepsies in electronic data sources.

PMID- 29588994
TI  - "Saved by the Bell": Near SUDEP during intracranial EEG monitoring.
AB  - SUDEP is the sudden unexpected death of a person with epilepsy, when no
      structural or toxicological cause of death can be found. The majority of
      witnessed cases are reported to be preceded by a convulsive seizure and postictal
      hypoventilation. Here, we report an 8-year-old girl with drug-resistant focal
      seizures secondary to a focal cortical dysplasia type IIb. While undergoing
      invasive intracranial monitoring with subdural and depth electrodes, she had a
      clinical apnea event recorded on video, followed by bradycardia, which required
      resuscitation. Her intracranial electroencephalogram (EEG) during the event
      showed diffuse slowing and attenuation of cortical activity, with bradycardia
      that responded to positive pressure ventilation with oxygen. This near SUDEP
      event was not preceded by either an electroclinical or electrographic seizure.
      This is the first report of a witnessed, near-SUDEP event during intracranial
      monitoring. It emphasizes the fact that near-SUDEP can occur without a preceding
      seizure.

PMID- 29588995
TI  - The adjunctive application of transcranial direct current stimulation in the
      management of de novo refractory epilepsia partialis continua in adolescent-onset
      POLG-related mitochondrial disease.
AB  - Focal status epilepticus in POLG-related mitochondrial disease is highly
      refractory to pharmacological agents, including general anesthesia. We report the
      challenges in managing a previously healthy teenager who presented with de novo
      epilepsia partialis continua and metabolic stroke resulting from the homozygous
      p.Ala467Thr POLG mutation, the most common pathogenic variant identified in the
      Caucasian population. We applied transcranial direct current stimulation (tDCS; 2
      mA; 20 min) daily as an adjunctive therapy because her focal seizures failed to
      respond to five antiepileptic drugs at maximal doses. The electrical and clinical
      seizures stopped after 3 days of tDCS. The second course of tDCS was administered
      for 14 days when the focal seizures re-emerged a month later. The patient
      tolerated the procedure well. Following 4 months of hospitalization and prolonged
      community rehabilitation, our patient has now returned to full-time education
      with support, and there is no report of cognitive deficit. We have demonstrated
      the safety and efficacy of tDCS in treating refractory focal motor seizures
      caused by mitochondrial disease.

PMID- 29588996
TI  - Postoperative EEG association with seizure recurrence: Analysis of the NIH
      epilepsy surgery database.
AB  - The epilepsy surgery database from 1984 to 2012 at the National Institutes of
      Health (NIH) was reviewed to determine the association of postoperative
      electroencephalography (EEG) with seizure recurrence. Eighty-three patients were
      analyzed, with 41 having at least 5 years of follow-up. The relationship between
      epileptiform postoperative EEG findings and seizure recurrence at 1, 2, and 5
      years was not significant, despite a significant decrease in abnormal EEG
      recordings after surgery. Clinicians use a variety of tools to predict seizure
      recurrence following epilepsy surgery to guide medication management and to
      modulate patient expectations. EEG is but one tool for assessing the likelihood
      of seizure recurrence following epilepsy surgery.

PMID- 29588998
TI  - Exploration of bulk and interface behavior of gas molecules and 1-butyl-3
      methylimidazolium tetrafluoroborate ionic liquid using equilibrium and
      nonequilibrium molecular dynamics simulation and quantum chemical calculation.
AB  - Ionic liquids (ILs) show brilliant performance in separating gas impurities, but
      few researchers have performed an in-depth exploration of the bulk and interface
      behavior of penetrants and ILs thoroughly. In this research, we have performed a
      study on both molecular dynamics (MD) simulation and quantum chemical (QC)
      calculation to explore the transport of acetylene and ethylene in the bulk and
      interface regions of 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]
      [BF4]). The diffusivity, solubility and permeability of gas molecules in the bulk
      were researched with MD simulation first. The subdiffusion behavior of gas
      molecules is induced by coupling between the motion of gas molecules and the
      ions, and the relaxation processes of the ions after the disturbance caused by
      gas molecules. Then, QC calculation was performed to explore the optical geometry
      of ions, ion pairs and complexes of ions and penetrants, and interaction
      potential for pairs and complexes. Finally, nonequilibrium MD simulation was
      performed to explore the interface structure and properties of the IL-gas system
      and gas molecule behavior in the interface region. The research results may be
      used in the design of IL separation media.

PMID- 29588999
TI  - First-principles study on thermodynamic stability of the hybrid interfacial
      structure of LiMn2O4 cathode and carbonate electrolyte in Li-ion batteries.
AB  - The solid electrolyte interphase (SEI) of Li-ion batteries (LIBs) has been
      extensively studied, with most research focused on the anode, because of its
      significant impact on the prolonged cycle life, initial capacity loss, and safety
      issues. Using first-principles density functional theory (DFT) calculations and
      ab initio molecular dynamics (AIMD) simulations with the Hubbard correction, we
      examine the thermodynamic structure prediction and electrochemical stability of a
      spinel LiMn2O4 cathode interfaced with a carbonate electrolyte. The electronic
      energy levels of frontier orbitals of the electrolyte and the work function of
      the cathode offer clear characterization of the interfacial reactions. Our
      results based on both DFT calculations and AIMD simulations propose that the
      proton transfer mechanism at the hybrid interface is essential for initiating the
      SEI layer formation on the LiMn2O4 surface. Our results can be useful for
      identifying design concepts in the development of stable and high capacity LIBs
      with optimized electrodes and high-performance electrolytes.

PMID- 29589001
TI  - Polysulfide-triggered fluorescent indicator suitable for super-resolution
      microscopy and application in imaging.
AB  - A new physiologically benign and cell membrane permeable BODIPY based molecular
      probe, MB-Sn, specifically senses intracellular hydrogen polysulfides (H2Sn, n >
      1) localized in the endoplasmic reticulum. This reagent is suitable for mapping
      the intracellular distribution of H2Sn by wide-field as well as super-resolution
      Structured Illumination Microscopy (SIM).

PMID- 29589000
TI  - Osteogenic nanostructured titanium surfaces with antibacterial properties under
      conditions that mimic the dynamic situation in the oral cavity.
AB  - The study aim was to assess the impact of different surface nanofeatures on
      otherwise smooth titanium surfaces on bacterial adhesion as well as on their
      osteogenic potential. Bacterial adhesion was assessed in the presence of saliva
      under static and dynamic conditions to approximate both sub- and supragingival
      conditions in the oral cavity as the gingival seal will be affected by
      implantation. The ultimate goal was to develop a surface that will reduce biofilm
      formation but still support osseointegration in vivo. To this end nanotubular or
      nanopitted surfaces were created on electropolished titanium via electrochemical
      anodization procedures. Sandblasted/acid etched surfaces (SBAE) were used as a
      microrough reference. Bacterial adhesion was studied using saliva-precoated
      samples with S. sanguinis as a typical early colonizer of the oral cavity;
      osteogenic differentiation was assessed with human bone marrow stromal cells.
      While bacterial adhesion was reduced on all microsmooth surfaces to an average of
      17% surface coverage compared to 61% on SBAE under static conditions, under
      dynamic conditions the nanopitted surface had a significant impact on bacterial
      adhesion. Here fluid flow removed all bacteria. By comparison, the reduction on
      the nanotubular surface was only similar to that of the SBAE reference. We
      hypothesise the underlying cause to be an effect of the surface morphology on the
      structure and composition of the saliva precoating that reduces its stability,
      giving rise to a self-cleaning effect. In addition, no negative influence on the
      osteogenic potential of the nanopitted surface could be determined by alkaline
      phosphatase activity, mineralization behaviour or gene expression; it remained on
      a par with the tissue culture plastic control. Thus, nanopitting seems to be a
      promising surface treatment candidate for dental implants to reduce infection
      related complications without compromising the implant integration.

PMID- 29589005
TI  - Finger-actuated microfluidic device for the blood cross-matching test.
AB  - A blood cross-matching test should be carried out to prevent a hemolytic
      transfusion reaction as the final verification step. To simplify complicated
      procedures of a conventional blood cross-matching test requiring bulky systems
      and skilled people, we present a finger-actuated microfluidic device for the
      blood cross-matching test. Although finger actuation is a simple action that
      anyone can easily accomplish, there would be a variation in the individual finger
      actuation that may induce the user-dependent errors of the device. Therefore, the
      working principle of the finger-actuated microfluidic device is newly designed to
      reduce the user-dependent errors by indirectly controlling the pressure of
      fluidic channels. The constant volume was repeatedly dispensed by pushing and
      releasing a pressure chamber regardless of the different pushed depths of the
      pressure chamber, the pushing time interval, and the end-users. The dispensed
      volume was linearly increased according to the number of pushing times applied to
      the pressure chamber and determined by adjusting the diameter of an actuation
      chamber. In addition, multiple fluids can be dispensed with a desirable ratio by
      pushing and releasing the pressure chamber. Finally, a finger-actuated
      microfluidic device for the blood cross-matching test was developed, which can
      simultaneously actuate four fluidic channels. After loading 50 MUL of whole blood
      samples from a donor and a recipient into two inlets of the device, the blood
      plasma from each individual was separated through the two plasma separation
      membranes. The blood cross-matching test results can be achieved by cross
      reacting the donor's blood plasma with the recipient's whole blood as well as the
      donor's whole blood with the recipient's blood plasma by pushing and releasing
      only a single pressure chamber within 10 min.

PMID- 29589006
TI  - Pretreatment with dihydroquercetin, a dietary flavonoid, protected against
      concanavalin A-induced immunological hepatic injury in mice and TNF-alpha/ActD
      induced apoptosis in HepG2 cells.
AB  - We have previously demonstrated the hepatoprotective effect of dihydroquercetin
      (DHQ) against concanavalin A (Con A)-induced immunological hepatic injury in
      mice. In this study, we investigated the immunoregulatory effects of DHQ on Con A
      induced liver injury in mice. DHQ administration significantly decreased the
      serum levels of alanine transaminase and aspartate transaminase, effectively
      prevented liver damage, and increased the survival rate of Con A-treated mice.
      Immunohistochemistry examination revealed that supplementation with DHQ obviously
      reduced infiltration of CD4+ and CD8+ T cells in the injured liver tissues.
      Furthermore, DHQ administration resulted in down-regulation of pro-inflammatory
      cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-10), the chemokine
      osteopontin, apoptosis factors (Fas and FasL), transcription factors that
      regulate Th cell differentiation (T-bet and GATA-3), perforin, granzyme B, and
      inducible nitric oxide synthase (iNOS). In vitro, treatment with DHQ protected
      HepG2 cells against TNF-alpha/ActD-induced apoptosis by inhibiting the activation
      of caspase-3, caspase-7, and caspase-8. In addition, DHQ reduced phosphorylation
      of NF-kB/p65, and inhibited the expressions of pro-apoptotic factors (p53 and
      Bax), while it up-regulated the expression of the anti-apoptotic factor Bcl-2.
      Our findings suggest that the immunosuppressive effects of DHQ ameliorated Con A
      mediated immunological liver injury by reducing the expression of pro
      inflammatory mediators and infiltration of CD4+ and CD8+ T cells in liver
      tissues, and DHQ protected HepG2 cells against TNF-alpha/ActD-induced apoptosis
      possibly via modulation of the caspase and NF-kB pathways.

PMID- 29589007
TI  - Double uranium oxo cations derived from uranyl by borane or silane reduction.
AB  - A new type of double uranium oxo cation [O-U-O-U-O]4+ is prepared by selective
      oxygen-atom abstraction from macrocyclic uranyl complexes using either boranes or
      silanes. A significant degree of multiple U[double bond, length as m-dash]O
      bonding is evident throughout the U2O3 core, but either trans-,cis- or trans
      ,trans-OUOUO motifs can be isolated as boron- or silicon-capped oxo complexes.
      Further controlled deoxygenation of the borylated system is also possible.

PMID- 29589008
TI  - Reactivity of bulky Ln(ii) amidinates towards P4, As4, and As4S4.
AB  - The reduction of P4, As4 and As4S4 (realgar) with the sterically encumbered
      reductants [(DippForm)2Ln(thf)2] (Ln = Sm, Yb; DippForm = {(2,6-iPr2C6H3)NC(H) =
      N(2,6-iPr2C6H3)}-) is reported. For the first time, purely f-element containing
      inverse inorganic sandwich complexes [{(DippForm)2Sm}2(MU2-eta4:eta4-E4)] (E = P,
      As), featuring a pi-aromatic cyclo [E4]2- middle deck, were obtained upon
      reaction with P4 and As4. The reaction with realgar leads to a cage disruption
      and the formation of the unusual species [{(DippForm)(DippForm-AsS2)}Ln(thf)].
      The reactivity of divalent Ln amidinates towards main group molecules is in
      comparison to metallocenes faster, more efficient and thus significantly
      influenced by the ligand environment. Experimental results are supported by DFT
      calculations.

PMID- 29589009
TI  - Solid state p-type dye sensitized NiO-dye-TiO2 core-shell solar cells.
AB  - Solid state p-type dye sensitized NiO-dye-TiO2 core-shell solar cells with an
      organic dye PB6 were successfully fabricated for the first time. With Al2O3 as an
      inner barrier layer, the recombination process between injected holes in NiO and
      injected electrons in TiO2 was significantly suppressed and the charge transport
      time was also improved.

PMID- 29589010
TI  - Structure and nitrite reduction reactivity study of bio-inspired copper(i)-nitro
      complexes in steric and electronic considerations of tridentate nitrogen ligands.
AB  - Two copper(i)-nitro complexes [Tpm3-tBuCu(NO2)] (1) and [(Ph3P)2N][Tp3
      tBuCu(NO2)] (2), containing steric bulky neutral tris(3-tert
      butylpyrazolyl)methane and anionic hydrotris(3-tert-butylpyrazolyl)borate
      ligands, have been synthesized and characterized. Complex 2 adopts a unique
      kappa2-binding mode of Tp3-tBu around the copper(i)-nitro environment in the
      solid state and shows a four-coordinated tetrahedral geometry surrounded by a
      nitro and three pz3-tBu groups in solution. Both complexes 1 and 2 allow for the
      stoichiometric reduction of NO2- to NO with H+ addition. The results of this
      effort show that increasing steric bulk and electron donation properties on the
      nitrogen ancillary ligand will improve the nitrite reduction ability of the
      copper(i)-nitro model complexes.

PMID- 29589011
TI  - Interactions of gaseous molecules with X-ray photons and photoelectrons in AP-XPS
      study of solid surface in gas phase.
AB  - Studies of the surface of a catalyst in the gas phase via photoelectron
      spectroscopy is an important approach to establish a correlation between the
      surface of a catalyst under reaction conditions or during catalysis and its
      corresponding catalytic performance. Unlike the well understood interactions
      between photoelectrons and the atomic layers of a surface in ultrahigh vacuum
      (UHV) and the well-developed method of quantitative analysis of a solid surface
      in UHV, a fundamental understanding of the interactions between X-ray photons and
      gaseous molecules and between photoelectrons and molecules of the gas phase in
      ambient pressure X-ray photoelectron spectroscopy (AP-XPS) is lacking. Through
      well designed experiments, here the impact of the interactions between
      photoelectrons and gaseous molecules and interactions between X-ray photons and
      gaseous molecules on the intensity of the collected photoelectrons have been
      explored. How the changes in photoelectron intensity resulting from these
      interactions influence measurement of the authentic atomic ratio of element M to
      A of a solid surface has been discussed herein, and methods to correct the
      measured nominal atomic ratio of two elements of a solid surface upon travelling
      through a gas phase to its authentic atomic ratio have been developed.

PMID- 29589012
TI  - Influence of a cobalt additive in spiro-OMeTAD on charge recombination and
      carrier density in perovskite solar cells investigated using impedance
      spectroscopy.
AB  - The role of additives in spiro-OMeTAD as a hole transport material (HTM) has been
      found to be vitally important for achieving decent photovoltaic performance of
      perovskite solar cells (PSCs). Four spiro-OMeTAD recipes with controlled
      concentrations of additives are studied in the context of PSCs. It is found that
      a small change in the concentration of additives results in a huge difference in
      the overall power conversion efficiency, which stems from the distinct charge
      extraction process in PSCs. Furthermore, the effect of the third additive, a
      cobalt complex (FK102, Co(iii)TFSI), on the carrier density and charge
      recombination in PSCs is extensively investigated. It is found that the presence
      of the cobalt additive can significantly improve the photovoltaic performance of
      PSCs via the suppression of charge recombination at the interface of the
      perovskite layer and the HTM layer, which leads to a more than doubled power
      conversion efficiency.

PMID- 29589013
TI  - Framework flexibility of ZIF-8 under liquid intrusion: discovering time-dependent
      mechanical response and structural relaxation.
AB  - The structural flexibility of a topical zeolitic imidazolate framework with
      sodalite topology, termed ZIF-8, has been elucidated through liquid intrusion
      under moderate pressures (i.e. tens of MPa). By tracking the evolution of water
      intrusion pressure under cyclic conditions, we interrogate the role of the gate
      opening mechanism controlling the size variation of the pore channels of ZIF-8.
      Interestingly, we demonstrate that its channel deformation is recoverable through
      structural relaxation over time, hence revealing the viscoelastic mechanical
      response in ZIF-8. We propose a simple approach employing a glycerol-water
      solution mixture, which can significantly enhance the sensitivity of intrusion
      pressure for the detection of structural deformation in ZIF-8. By leveraging the
      time-dependent gate-opening phenomenon in ZIF-8, we achieved a notable
      improvement (50%) in energy dissipation during multicycle mechanical deformation
      experiments.

PMID- 29589014
TI  - A thermo-responsive structural switch and colossal anisotropic thermal expansion
      in a chiral organic solid.
AB  - Trianglimine, a chiral triangular-shaped hexaimine, exists in at least three
      apohost polymorphic forms. Form I had been previously obtained by crystallisation
      from a mixture of dichloromethane and acetonitrile and we have now crystallised
      Form II from acetone. Both forms possess similar packing arrangements, but Form
      II undergoes a reversible phase transition to Form III, as well as colossal
      anisotropic positive thermal expansion. Form I does not exhibit any remarkable
      thermal properties.

PMID- 29589015
TI  - Fabrication of a hierarchical NiO/C hollow sphere composite and its enhanced
      supercapacitor performance.
AB  - A hierarchical NiO/C hollow sphere composite (NiO/C-HS) was prepared via semi
      sacrificial template-assisted hydrothermal and calcination methods. NiO/C-HS,
      with well-dispersed NiO nanosheets supported by carbon hollow spheres, exhibited
      excellent electrochemical performance. The method was heuristic for the design of
      other composites and suitable for ameliorating the poor stability of transition
      metal oxides.

PMID- 29589016
TI  - On-surface synthesis of polyethylenedioxythiophene.
AB  - On-surface synthesis of conjugated polymers is made challenging by the need to
      promote the desired reaction while preventing or minimizing unwanted ancillary
      reactions that compromise the product integrity. We perform a comprehensive study
      of the reactions of 2,5-dichloro-3,4-ethylenedioxythiophene on coinage metal
      surfaces, and demonstrate that only on Ag(111) can we obtain a planar polymer
      product, polyethylenedioxythiophene (PEDOT).

PMID- 29589017
TI  - One-pot production of porous assemblies by PISA of star architecture copolymers:
      a simulation study.
AB  - The polymerization-induced self-assembly (PISA) process of star architecture
      copolymers is studied by dissipative particle dynamics and a reaction model.
      According to the simulation results, the porous vesicles can be produced directly
      by PISA of these copolymers. Average pore size and distribution of pore size can
      be influenced by alphaAS (the solubility between solvophilic blocks and solvent)
      and alphaAB (the solubility between solvophilic blocks and solvophobic blocks),
      while different self-assembly progress can be observed at different alphaAS and
      alphaAB. In addition, the star architecture can promote the formation of porous
      vesicles compared with linear copolymers. The steric effect of two solvophobic
      chains is verified as the key factor in formation of the porous vesicles. Further
      enhancement of such an effect can widen the range of alphaAS for production of
      porous vesicles, accompanied by a shrinkage of the range of alphaAB and a large
      reduction of pore size distribution. This work provides deeper understanding of
      the PISA of star architecture copolymers and is instructive in the experimental
      production of porous nano-materials.

PMID- 29589018
TI  - Regulating the local pH level of titanium via Mg-Fe layered double hydroxides
      films for enhanced osteogenesis.
AB  - Hard tissue implant materials which can cause a suitable alkaline
      microenvironment are thought to be beneficial for stimulating osteoblast
      differentiation while suppressing osteoclast generation. To make the local pH
      around the interface between materials and cells controllable, we prepared a
      series of Mg-Fe layered double hydroxide (LDH) films on acid-etched pure titanium
      surfaces via hydrothermal treatment. By adjusting the Mg/Fe proportion ratio, the
      interlayer spacing of Mg-Fe LDHs was regulated, making their OH- exchange
      abilities adjustable, and this ultimately resulted in a microenvironment with a
      controllable pH value. In vitro experiments demonstrated that the Mg-Fe LDH film
      modified titanium surface possessed good biocompatibility and osteogenic
      activity, especially the Mg-Fe LDH film with Mg/Fe proportion ratio of 4, which
      could form a suitable alkaline microenvironment for the growth and osteogenetic
      differentiation of stem cells. These results demonstrate the potential
      application of the prepared Mg-Fe LDH films in enhancing the osteogenesis of
      implant materials while providing a new way into the design of controllable
      alkaline environment.

PMID- 29589019
TI  - Synthesis, properties, and formation mechanism of Mn-doped Zn2SiO4 nanowires and
      associated heterostructures.
AB  - In this work, we have put forth a facile hydrothermal approach to synthesize an
      array of one-dimensional (1D) Mn-doped Zn2SiO4 nanostructures. Specifically, we
      have probed and correlated the effects of controllable reaction parameters such
      as the pH and Mn dopant concentrations with the resulting crystal structures and
      morphologies of the products obtained. Based upon our results, we find that
      careful tuning of the pH versus the Mn dopant level gives rise to opposite trends
      with respect to the overall size of the resulting one-dimensional nanostructures.
      Significantly, we have highlighted the role of the Mn dopant ion concentration as
      a potentially generalizable reaction parameter in solution-based synthesis for
      controlling morphology and hence, the observed optical behavior. Indeed, such a
      strategy can be potentially generalized to systems such as but not limited to Mn
      doped ZnS, CdS, and CdSe quantum dots (QD), which, to the best of our knowledge,
      denote promising candidates for a variety of optoelectronic applications.
      Specifically, we have carefully optimized the synthesis conditions in order to
      generate a series of chemically well-defined Mn-doped Zn2SiO4 not only possessing
      Mn concentrations ranging from 3% to 8% but also characterized by highly
      crystalline, monodisperse wire-like motifs measuring ~30 nm in diameter and ~700
      nm in length. Optically, the photoluminescence signals associated with the 1D
      series yielded a volcano-shaped relationship between PL intensities and the Mn
      dopant level. In additional experiments, we have immobilized CdSe quantum dots
      (QDs) onto the external surfaces of our as-synthesized Mn-doped Zn2SiO4
      nanowires, in order to form novel composite heterostructures. The optical
      properties of the CdSe QD-Mn:Zn2SiO4 heterostructures have been subsequently
      examined. Our results have demonstrated the likely co-existence of both energy
      transfer and charge transfer phenomena between the two constituent components of
      our as-prepared composites. Specifically, when both components are photoexcited,
      both energy transfer and charge transfer were found to plausibly occur, albeit in
      opposite directions. When the CdSe QDs are excited alone for example, charge
      transfer probably takes place from the CdSe QDs to the dopant Mn2+ ions. We
      believe that our as-processed heterostructures are therefore promising as a
      tunable light-harvesting motif. Essentially, these materials have broadened the
      effective light absorption range for optical 'accessibility', not only through
      their incorporation of dopant-tunable Zn2SiO4 possessing complementary absorption
      properties to those of the QDs but also through their integration of CdSe QDs
      with size-tailorable optical behavior.

PMID- 29589020
TI  - Core-shell structured MnSiO3 supported with CNTs as a high capacity anode for
      lithium-ion batteries.
AB  - Metal silicates are good candidates for use in lithium ion batteries (LIBs),
      however, their electrochemical performance is hindered by their poor electrical
      conductivity and volume expansion during Li+ insertion/desertion. In this work,
      one-dimensional core-shell structured MnSiO3 supported with carbon nanotubes
      (CNTs) (referred to as CNT@MnSiO3) with good conductivity and electrochemical
      performance has been successfully synthesized using a solvothermal process under
      moderate conditions. In contrast to traditional composites of CNTs and
      nanoparticles, the CNT@MnSiO3 composite in this work is made up of CNTs with a
      layer of MnSiO3 on the surface. The one-dimensional CNT@MnSiO3 nanotubes provide
      a useful channel for transferring Li+ ions during the discharge/charge process,
      which accelerates the Li+ diffusion speed. The CNTs inside the structure not only
      enhance the conductivity of the composite, but also prevent volume expansion. A
      high reversible capacity (920 mA h g-1 at 500 mA g-1 over 650 cycles) and good
      rate performance were obtained for CNT@MnSiO3, showing that this strategy of
      synthesizing coaxial CNT@MnSiO3 nanotubes offers a promising method for preparing
      other silicates for LIBs or other applications.

PMID- 29589021
TI  - Structural coloration of transmission light through self-aligned and
      complementary plasmonic nanostructures.
AB  - Structural coloration of natural surfaces often originates from the change of
      reflected colors depending on the viewing or illumination angle. Recently, the
      structural coloration of nanoplasmonic structures has attracted a great deal of
      attention due to high compactness, robust stability and high color-tunability, as
      well as high sensitivity to the incidence angle. Here we report complementary
      plasmonic structures (CPS) for transmission structural coloration by tailoring a
      single spectral peak depending on the incidence angle of light. The CPS features
      self-aligned silver nanohole and nanodisk arrays, supported by dielectric
      nanopillar arrays of hydrogen silsesquioxane. Unlike the conventional hybridized
      nanostructures of plasmonic nanohole and nanodisk arrays, the nanodisks of CPS
      effectively attenuate undesired spectral peaks of nanoholes by exploiting an
      extinction peak of nanodisks, serving as a spectral suppressor. As a result, a
      single transmission spectral peak becomes red-shifted from 736 nm to 843 nm as
      the incidence angle varies from 0 degrees  to 30 degrees . This unique
      configuration provides a new direction for tunable filters that can be utilized
      for compact multispectral or hyperspectral imaging applications.

PMID- 29589022
TI  - Optimizing the motion of a folding molecular motor in soft matter.
AB  - We use molecular dynamics simulations to investigate the displacement of a
      periodically folding molecular motor in a viscous environment. Our aim is to find
      significant parameters to optimize the displacement of the motor. We find that
      the choice of a massy host or of small host molecules significantly increase the
      motor displacements. While in the same environment, the motor moves with hopping
      solid-like motions while the host moves with diffusive liquid-like motions, a
      result that originates from the motor's larger size. Due to hopping motions,
      there are thresholds on the force necessary for the motor to reach stable
      positions in the medium. These force thresholds result in a threshold in the size
      of the motor to induce a significant displacement, that is followed by plateaus
      in the motor displacement.

PMID- 29589024
TI  - Vanadyl dithiolate single molecule transistors: the next spintronic frontier?
AB  - On the road towards quantum devices, chemistry can offer elementary pieces with a
      built-in function, like [TbPc2]- which functions as a molecular transistor for
      nuclear spin detection. We argue that a large class of molecules have similar
      potential. In particular, we review the recent progress regarding highly coherent
      spin qubits based on vanadium dithiolate complexes. We propose their use as
      single molecule transistors to read and control a triple nuclear spin qubit,
      which could enable a low-current nuclear spin detection scheme by means of a spin
      valve effect.

PMID- 29589025
TI  - Unsymmetrical diborane(4) derivatives by copper mediated B-B coupling.
AB  - A novel, versatile and modular route to unsymmetrical diborane(4) derivatives
      bearing either two different diol moieties or one diol and one diamine moiety is
      presented. Utilising the very basic approach of reacting a boron nucleophile with
      a boron electrophile to establish the B-B bond allows a simple variation of the
      two individual boron moieties. The copper(i) boryl complexes used as nucleophilic
      boron sources are readily accessible from commercially available symmetrical
      diborane(4) derivatives, whilst equally readily available boron halide
      derivatives are used as electrophiles. Seven previously inaccessible diborane(4)
      derivatives were obtained and fully characterised, including single crystal X-ray
      structure determinations, illustrating the broad scope of the method.

PMID- 29589026
TI  - A robust and stretchable superhydrophobic PDMS/PVDF@KNFs membrane for oil/water
      separation and flame retardancy.
AB  - The wide application of superhydrophobic membranes has been limited due to their
      complicated preparation technology and weak durability. Inspired by the
      mechanical flexibility of nanofibrous biomaterials, nanofibrils have been
      successfully generated from Kevlar, which is one of the strongest synthetic
      fibers, by appropriate hydrothermal treatment. In this study, a robust
      superhydrophobic PDMS/PVDF@KNFs membrane is prepared via a simple one-step
      process and subsequent curing without combination with inorganic fillers. The as
      prepared PDMS/PVDF@KNFs membrane not only shows efficient oil/water separation
      ability and oil absorption capacity but also has excellent superhydrophobicity
      stability after deformation. The resultant membrane shows stretchability,
      flexibility and flame retardance because of the reinforcing effect and the
      excellent flame retardancy of Kevlar. We believe that this simple fabrication of
      PDMS/PVDF@KNFs has promising applications in filtering membranes and wearable
      devices.

PMID- 29589027
TI  - Correction: Synthesis of the 10-oxabicyclo[5.2.1]decane framework present in
      bioactive natural products.
AB  - Correction for 'Synthesis of the 10-oxabicyclo[5.2.1]decane framework present in
      bioactive natural products' by Angel M. Montana et al., Org. Biomol. Chem., 2018,
      16, 1557-1580.

PMID- 29589028
TI  - Synthesis and aggregation behaviour of single-chain, 1,32-alkyl branched
      bis(phosphocholines): effect of lateral chain length.
AB  - Three novel single-chain bis(phosphocholines) bearing two lateral alkyl chains of
      variable length next to the headgroup have been synthesized as model lipids for
      naturally occurring archaeal membrane lipids. The synthesis was realized using
      the Cu-catalyzed Grignard bis-coupling reaction of a primary bromide as a side
      part and a 1,omega-dibromide as a centre part. We could show that the aggregation
      behaviour of the resulting bolalipids strongly depends on the length of the
      lateral alkyl chain: the C3-branched bolalipid self-assembles into lamellar
      sheets, whereas the C6- and C9-analogues form nanofibres. The lamella-forming
      bolalipids could be used in the future to prepare stable and tailored liposomes
      for oral drug delivery.

PMID- 29589029
TI  - Molecular dynamics study of the LCST transition in aqueous poly(N-n
      propylacrylamide).
AB  - The breadth of technological applications of smart polymers relies on the
      possibility of tuning their molecular structure to respond to external stimuli.
      In this context, N-substituted acrylamide-based polymers are widely studied
      thermoresponsive polymers. Poly(N-n-propylacrylamide) (PNnPAm), which is a
      structural isomer of the poly(N-isopropylacrylamide) (PNIPAm) exhibits however, a
      lower phase transition in aqueous solution. In this work, we use all-atom
      molecular dynamics simulations of PNnPAm in aqueous solutions to study, from a
      microscopic point-of-view, the influence of chain size and concentration on the
      LCST of PNnPAm. Our analysis shows that the collapse of a single oligomer of
      PNnPAm upon heating is dependent on the chain length and corresponds to a complex
      interplay between hydration and intermolecular interactions. Analysis of systems
      with multiple chains shows an aggregation of PNnPAm chains above the LCST.

PMID- 29589032
TI  - Enhanced solar water-splitting activity of novel nanostructured Fe2TiO5
      photoanode by electrospray and surface F-modification.
AB  - Fe2TiO5 is recognized as a novel photoanode material for solar water splitting.
      However, it has been seldom studied as a photoelectrode by itself, and its
      practical performance still needs to be improved. Herein, nanostructured Fe2TiO5
      photoanode is prepared by the electrospray technique. The effects of the
      synthesis parameters on the photoelectrochemical water splitting activity are
      studied including the substrate temperature and film thickness. In addition,
      surface F-modification is applied on pure Fe2TiO5 to further improve its
      photoelectrochemical performance. Also, the water splitting photocurrent of F
      treated Fe2TiO5 increases to 0.4 mA cm-2 at 1.23 VRHE, which is higher than that
      of pristine Fe2TiO5. X-ray photoelectron spectroscopy confirms the formation of
      surface Ti-F bonds after surface F-treatment, which facilitates the transfer of
      holes and the breakage of O-H bond under illumination. The enhanced performance
      can be attributed to a synergetic effect of nanoarchitecture and surface F
      modification. Therefore, the nanoarchitecture assisted by surface F-modification
      offers an effective strategy to prepare high-efficiency nanostructured complex
      metal oxides for solar water splitting.

PMID- 29589033
TI  - Diastereoselective reduction of the tricarbonyl moiety in bicyclic tetramates
      giving pyroglutamates.
AB  - The reduction of C(6)-acyl bicyclic tetramic acids has been achieved with
      complete diastereoselectivity via catalytic hydrogenation using PtO2. The
      resulting pyroglutamates had potent antibacterial and anticancer properties and
      will allow the preparation of simple mimics of pyroglutamate-containing natural
      products.

PMID- 29589034
TI  - Melatonin-directed micellization: a case for tryptophan metabolites and their
      classical bioisosteres as templates for the self-assembly of bipyridinium-based
      supramolecular amphiphiles in water.
AB  - The bulk solution properties of amphiphilic formulations are derivative of their
      self-assembly into higher ordered supramolecular assemblies known as micelles and
      of their ordering at the air-water interface. Exerting control over the surface
      active properties of amphiphiles and their propensity to aggregate in pure water
      is most often fine-tuned by covalent modification of their molecular structure.
      Nevertheless structural constraints which limit the performance of amphiphiles do
      emerge when trying to develop more sophisticated systems which undergo for
      example, shape-defined controlled assembly and/or respond to external stimuli. In
      this regard, the template-modulated assembly of the so-called "supramolecular
      amphiphiles" continues to make progress ordering molecules that otherwise have
      very little to no driving force to aggregate in a prescribed manner in aqueous
      solutions. Herein we describe the template-modulated micellization and ordering
      at the air-water interface of bipyridinium-based supramolecular amphiphiles
      triggered by host-guest interactions with high specificity for the
      neurotransmitter melatonin over its biosynthetic synthon l-tryptophan and the
      thermodynamic parameters governing the template-modulated micellization process.
      When bound to the bipyridinium units of micellized surfactant molecules,
      melatonin effectively serves as "molecular glue" capable of lowering the CMC by
      52% as compared to untemplated solutions. Analysis of this system suggests that a
      hallmark of donor-acceptor template-modulated micellization in water is a strong
      positively correlated temperature dependence of the CMC and the absence of a U
      shaped CMC-temperature curve. Our findings make a case for the incorporation of l
      tryptophan-based metabolites and their classical synthetic pharmaceutical
      bioisosteres as potential targets/components of donor-acceptor CT-based
      supramolecular amphiphile systems/materials operating in water.

PMID- 29589035
TI  - Unravelling the nucleation mechanism of bimetallic nanoparticles with composition
      tunable core-shell arrangement.
AB  - The structure and atomic ordering of Au-Ag nanoparticles grown in the gas phase
      are determined by a combination of HAADF-STEM, XPS and Refl-XAFS techniques as a
      function of composition. It is shown consistently from all the techniques that an
      inversion of chemical ordering takes place by going from Au-rich to Ag-rich
      compositions, with the minority element always occupying the nanoparticle core,
      and the majority element enriching the shell. With the aid of DFT calculations,
      this composition-tunable chemical arrangement is rationalized in terms of a four
      step growth process in which the very first stage of cluster nucleation plays a
      crucial role. The four-step growth mechanism is based on mechanisms of a general
      character, likely to be applicable to a variety of binary systems besides Au-Ag.

PMID- 29589036
TI  - Hierarchical nanosheet-based Bi2MoO6 microboxes for efficient photocatalytic
      performance.
AB  - Hierarchical nanosheet-based Bi2MoO6 microboxes are synthesized by a facile
      template-assisted strategy. MnCO3 microcubes are prepared as templates for the
      growth of Bi2MoO6 nanosheets and then etched by using HCl aqueous solution. In
      particular, the hierarchical Bi2MoO6 microboxes provide a large surface area, and
      facilitate visible-light absorption and charge separation, demonstrating
      efficient photocatalytic performance. This work highlights a new method to
      prepare hollow nanosheet-built Bi2MoO6 structures with high photocatalytic
      properties.

PMID- 29589037
TI  - Gold(i)-catalyzed diastereoselective synthesis of 1-alpha-oxybenzyl-1H-indenes.
AB  - The gold(i)-catalyzed oxycyclization of beta-aryl monosubstituted o
      (alkynyl)styrenes gives rise to 1-alpha-methoxy or 1-alpha-hydroxybenzyl-1H
      indenes in a diastereospecific way. In contrast to beta,beta-disubstituted o
      (alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific
      reaction supports the higher contribution of a gold intermediate with a
      cyclopropylcarbene-like character.

PMID- 29589038
TI  - Shift work and cardiovascular disease - do the new studies add to our knowledge?

PMID- 29589039
TI  - Blunt traumatic injury during pregnancy: a descriptive analysis from a level 1
      trauma center.
AB  - PURPOSE: The precise incidence of trauma in pregnancy is not well-known, but
      trauma is estimated to complicate nearly 1 in 12 pregnancies and it is the
      leading non-obstetrical cause of maternal death. METHODS: A retrospective study
      of all pregnant women presented to national level 1 trauma center from July 2013
      to June 2015 was conducted. Descriptive and inferential statistics applied for
      data analysis. RESULTS: Across the study period, a total of 95 pregnant women
      were presented to the trauma center. The average incidence rate of traumatic
      injuries was 250 per 1000 women of childbearing age presented to the Hamad Trauma
      Center. The mean age of patients was 30.4 +/- SD 5.6 years, with age ranging from
      20 to 42 years. The mean gestational age at the time of injury was 24.7 +/- 8.7
      weeks which ranged from 5 to 37 weeks. The majority (47.7%) was in the third
      trimester of the pregnancy. In addition, the large majority of injuries was due
      to MVCs (74.7%) followed by falls (15.8%). CONCLUSIONS: Trauma during pregnancy
      is not an uncommon event particularly in the traffic-related crashes. As it is a
      complex condition for trauma surgeons and obstetrician, an appropriate management
      protocol and multidisciplinary team are needed to improve the outcome and save
      lives of both the mother and fetus.

PMID- 29589040
TI  - [Global and national strategies against antibiotic resistance].
AB  - Antimicrobial resistance (AMR) is increasingly perceived as a global health
      problem. To tackle AMR effectively, a multisectoral one health approach is
      needed. We present some of the initiatives and activities at the national and
      global level that target the AMR challenge. The Global Action Plan on AMR, which
      has been developed by the World Health Organization (WHO), in close collaboration
      with the Food and Agriculture Organization of the United Nations (FAO) and the
      World Organisation for Animal Health (OIE) is considered a blueprint to combat
      AMR. Member states endorsed the action plan during the World Health Assembly 2015
      and committed themselves to develop national action plans on AMR. The German
      Antibiotic Resistance Strategy (DART 2020) is based on the main objectives of the
      global action plan and was revised and published in 2015. Several examples of the
      implementation of DART 2020 are outlined here.

PMID- 29589042
TI  - [Hemostyptics for treatment of junctional vascular injuries : Management of
      traumatic vascular injuries at the transition from trunk to extremities].
AB  - BACKGROUND: Uncontrolled post-traumatic bleeding is still the leading cause of
      death among trauma patients. In situations of mass casualty incidents (MASCAL)
      and military conflicts the treatment of uncontrolled critical bleeding is a
      challenge and associated with a worse outcome due to the austere environment;
      however, even under optimal treatment circumstances in situations of individual
      medicine the severity of vascular trauma is underestimated. As a consequence,
      this leads to a poorer prognosis for patients with (vascular) injuries. From this
      perspective it was reasonable to intensify the training of physicians, paramedics
      (Advanced Trauma Life Support(c)) and first responders (Hartford consensus) for
      handling of critical bleeding in traumatized patients. Furthermore, the main
      emphasis of the revised S3 clinical guidelines on polytrauma/severely injured
      treatment from 2016 of the German Society for Trauma Surgery is on the
      preclinical treatment. Despite a renaissance and increasing use of tourniquets,
      the treatment of bleeding in the transition from the trunk to the extremities
      (junctional vascular injuries), which are inaccessible to placing a tourniquet,
      remains a problem. CONCLUSION: It was the military that in addition to the
      development of special tourniquets, intensified research programs and the
      implementation of hemostatic devices and dressings in this anatomical region.
      This article deals with junctional vascular injuries at the transition between
      the trunk and the extremities. In addition to the anatomical situation, this
      article gives the reader an overview of the currently available hemostyptics and
      their mode of action.

PMID- 29589041
TI  - Genome-wide association mapping for resistance to leaf rust, stripe rust and tan
      spot in wheat reveals potential candidate genes.
AB  - KEY MESSAGE: Genome-wide association mapping in conjunction with population
      sequencing map and Ensembl plants was used to identify markers/candidate genes
      linked to leaf rust, stripe rust and tan spot resistance in wheat. Leaf rust
      (LR), stripe rust (YR) and tan spot (TS) are some of the important foliar
      diseases in wheat (Triticum aestivum L.). To identify candidate resistance genes
      for these diseases in CIMMYT's (International Maize and Wheat Improvement Center)
      International bread wheat screening nurseries, we used genome-wide association
      studies (GWAS) in conjunction with information from the population sequencing map
      and Ensembl plants. Wheat entries were genotyped using genotyping-by-sequencing
      and phenotyped in replicated trials. Using a mixed linear model, we observed that
      seedling resistance to LR was associated with 12 markers on chromosomes 1DS, 2AS,
      2BL, 3B, 4AL, 6AS and 6AL, and seedling resistance to TS was associated with 14
      markers on chromosomes 1AS, 2AL, 2BL, 3AS, 3AL, 3B, 6AS and 6AL. Seedling and
      adult plant resistance (APR) to YR were associated with several markers at the
      distal end of chromosome 2AS. In addition, YR APR was also associated with
      markers on chromosomes 2DL, 3B and 7DS. The potential candidate genes for these
      diseases included several resistance genes, receptor-like serine/threonine
      protein kinases and defense-related enzymes. However, extensive LD in wheat that
      decays at about 5 * 107 bps, poses a huge challenge for delineating candidate
      gene intervals and candidates should be further mapped, functionally
      characterized and validated. We also explored a segment on chromosome 2AS
      associated with multiple disease resistance and identified seventeen disease
      resistance linked genes. We conclude that identifying candidate genes linked to
      significant markers in GWAS is feasible in wheat, thus creating opportunities for
      accelerating molecular breeding.

PMID- 29589043
TI  - [Tinea capitis and onychomycosis due to Trichophyton soudanense : Successful
      treatment with fluconazole-literature review].
AB  - Two African girls who moved to Germany only 4 weeks ago presented to the
      dermatological office with itchy and scaling skin lesions of the scalp and the
      thighs. The entire scalp of both girls was affected by a white, dry dandruff and
      a squamous crust. Dry centrifugal spreading erythematosquamous lesions were found
      on the thighs. The surface of the left thumbnail of the younger girl was whitish.
      The Blancophor(r) preparations which were performed under the suspicion of a
      tinea capitis et corporis and onychomycosis from skin scrapings of the scalp and
      the thighs, and from the thumbnail of the younger child were positive.
      Cultivation of three samples from the affected body sites-hair, skin and nail
      revealed Trichophyton (T.) soudanense. For confirmation of the species
      identification, the isolates were subject of sequencing of ITS region of the rDNA
      and also of the translation elongation factor 1 alpha (TEF 1 alpha) gene. The
      phylogenetic analysis of the strains-the dendrogram of fungal strains
      demonstrated the genetic differences between T. soudanense and T. rubrum. In
      contrast, sequencing of the TEF 1 alpha gene did not allow any discrimination
      between T. soudanense and T. rubrum. Both girls were treated orally with
      fluconazole. For topical treatment of both girls, ciclopirox olamine solution and
      terbinafine cream were administered, each once daily. After 8 weeks oral
      fluconazole therapy the dermatomycoses of skin, scalp, and thumbnail of both
      children were completely healed. Currently, in Germany and Europe, in immigrants
      from West African countries (e. g., from Angola) dermatophytoses due to T.
      soudanense have to be expected. Cultural identification of the pathogen is
      relatively simple. However, only molecular methods allow the exact discrimination
      of T. violaceum and T. rubrum.

PMID- 29589045
TI  - Polycyclic Aromatic Hydrocarbons in Urban Soil in the Semi-arid City of Xi'an,
      Northwest China: Composition, Distribution, Sources, and Relationships with Soil
      Properties.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment. This
      study collected a total of 62 urban soil samples from the typical semi-arid city
      of Xi'an in Northwest. They were analyzed for the composition, distribution, and
      sources of PAHs as well as the relationships with soil properties. The sum of 16
      individual PAHs (?16PAHs) ranged from 390.6 to 10,652.8 MUg/kg with a mean of
      2052.6 MUg/kg. The average ?16PAHs decreased in the order of the third ring road
      (2321.1 MUg/kg) > the first ring road (1893.7 MUg/kg) > the second ring road
      (1610.0 MUg/kg), and in the order of industrial areas (3125.6 MUg/kg) > traffic
      areas (2551.6 MUg/kg) > educational areas (2414.4 MUg/kg) > parks (1649.5 MUg/kg)
      > mixed commercial and traffic areas (1332.8 MUg/kg) > residential areas (1031.0
      MUg/kg). The most abundant PAHs in the urban soil were 3- to 5-ring PAHs.
      Elevated levels of PAHs were found in industrial and traffic areas from the east
      and west suburbs and the northwest corner of Xi'an as well as the northeast
      corner in the urban district of Xi'an. PAHs in the urban soil were mainly related
      to the combustion of fossil fuel (i.e., coal, gasoline, diesel, and natural gas)
      and biomass (i.e., grass and wood) (variance contribution 57.2%) as well as the
      emissions of petroleum and its products (variance contribution 29.9%). Soil
      texture and magnetic susceptibility were the main factors affecting the
      concentration of PAHs in urban soil. Meanwhile, this study suggested that the
      single, rapid, and nondeductive magnetic measurements can be an indicator of soil
      pollution by PAHs.

PMID- 29589044
TI  - [The role of innate immunity in otitis media].
AB  - Otitis media (OM) belongs to the most common pediatric diseases and causes more
      medical contacts, surgical interventions, and drug prescriptions than any other
      infectious disease. Recent findings have identified a critical role of innate
      immunity in recovery from OM. The middle ear mucosa identifies invading pathogens
      by sensing pathogen-associated molecule patterns (PAMPs) via pattern recognition
      receptors such as the Toll-like receptors (TLRs). They generate immediate
      antimicrobial responses and cytokine release, leading to an inflammatory reaction
      as seen in acute or chronic OM. Cross-talk between TLRs can enhance or suppress
      the healing process in the middle ear. In order to prevent over-activation on the
      one hand and insufficient immune response on the other, the signaling network
      between different TLRs must be integrated and controlled by positive and negative
      feedback loops. This guarantees a proper immune response in the middle ear after
      infection. In this review, we focus on the involvement of the innate immune
      system and TLRs in OM, as well on their relevance for new vaccination strategies
      and immunotherapies.

PMID- 29589046
TI  - [Surgical therapy of ischiofemoral impingement by lateralizing intertrochanteric
      osteotomy].
AB  - OBJECTIVE: Lateralizing, derotating intertrochanteric varus osteotomy to increase
      the ischiofemoral space to counter painful impingement of the lesser trochanter
      and the os ischium with resulting entrapment of quadratus femoris muscle.
      INDICATIONS: Symptomatic ischiofemoral impingement (IFI) caused by Coxa valga et
      antetorta, Coxa valga or Coxa antetorta, or a short femoral neck.
      CONTRAINDICATIONS: Anatomic configuration suggestive of IFI in asymptomatic
      patients. Symptomatic IFI caused by another underlying pathology. Valgus
      deformity of the knee. SURGICAL TECHNIQUE: Measurement of femoral antetorsion.
      Planning of the osteotomy, lateralization, varus angle for correction, rotation
      and offset correction, leg length change, and osteosynthesis plate. General or
      spinal anesthesia in supine or lateral position. Skin incision (15 cm) beginning
      lateral of the greater trochanter tip, distally along the axis of the femur.
      Preparation onto the femur by L-shaped dissection of the vastus lateralis from
      the bone. A Kirschner(K-)wire is then positioned along the anterior femoral neck
      to designate the femoral neck antetorsion. A triangle set on the lateral femoral
      cortexis is used to determine the osteotomy angle. In the thus determined angle,
      a second K-wire is shot centrally along the femoral neck axis just inferior to
      its cranial cortex. About 5 mm distal to the second wire, the entry for the blade
      is prepared using a drill. Using the blade setting instrument, the blade is
      introduced into the femoral neck, then slightly pulled back. The rotation is then
      marked on the anterior femoral cortex proximal and distal to the planned
      osteotomy and the osteotomy is performed. A blade plate without displacement is
      impacted. The osteotomy is then reduced, the distal fragment pulled laterally
      onto the plate, and the screws inserted after compression of the osteotomy with a
      tension device. POSTOPERATIVE MANAGEMENT: Touch-toe bearing for 6 weeks, then
      radiological assessment of osteotomy healing before an increase in weight bearing
      (15 kg/week). Hip flexion limited to 90 degrees  for 6 weeks. Elective implant
      removal after 12-18 months. RESULTS: Studies of this lateralizing varus osteotomy
      have not been published. The 25-year results of the conventional derotating
      intertrochanteric varus osteotomy technique show good functional results and low
      complication rates, with non-union being the most common. Arthroscopic resection
      of the lesser trochanter has been reported as a surgical alternative in the
      treatment of IFI in case reports and small series. Advantages of the osteotomy
      are the restoration of biomechanics and preservation of iliopsoas tendon
      insertion.

PMID- 29589047
TI  - [Management of a massive cervical hematoma after insertion of a central venous
      catheter under tirofiban].
AB  - An 81-year-old woman with infarct-related cardiogenic shock was admitted to the
      cardiac catheterization laboratory. Coronary angiography revealed an occlusion of
      the ramus interventricularis anterior. Due to incomplete flow after the
      percutaneous coronary intervention with implantation of three coronary stents and
      high thrombus burden, tirofiban was given as a bail out therapy. A central venous
      catheter (CVC) aimed at the internal jugular vein was incidentally inserted in
      the common carotid artery, resulting in acute dyspnea and a hemorrhagic shock due
      to a massive cervical hematoma. Although the CVC is a frequently used
      intervention in critical care, the procedure still carries some risks of
      iatrogenic injury. Knowledge about the emergency management of CVC-associated
      complications is therefore essential.

PMID- 29589048
TI  - Efficiency of C3 and C4 Plant Derived-Biochar for Cd Mobility, Nutrient Cycling
      and Microbial Biomass in Contaminated Soil.
AB  - Biochar is considered a novel soil amendment to reduce metal mobility, but its
      influence on soil chemical and biochemical properties is not fully understood. In
      the present study, biochar derived from rice straw (RSB), rice hull (RHB), and
      maize stover (MSB) was used to evaluate comparative efficiency on Cd mobility and
      soil biochemical properties. Ammonium nitrate extractable Cd significantly
      decreased among all the applied biochar types and application rates. The European
      Community Bureau of Reference (BCR) technique showed significant decrease in acid
      soluble Cd by 24%-32%, 19%-23%, and 22%-27% for RSB, RHB, and MSB, respectively
      at the 1.5% and 3% rate. However, the concentration of Cd in the residual
      increased by 38%, 35% and 36% for RSB, RHB and MSB, respectively at a 3%
      application rate. Soil microbial biomass (C and N) and inorganic nitrogen forms
      (NH4 and NO3) significantly increased among all biochar applications. Overall,
      RSB demonstrated positive results as soil amendments for Cd immobilization,
      increasing soil nutrient availability, and enhancing soil microbial biomass.

PMID- 29589049
TI  - Inferior outcome of revision of unicompartmental knee arthroplasty to total knee
      arthroplasty compared with primary total knee arthroplasty: systematic review and
      meta-analysis.
AB  - PURPOSE: The purpose of this study was to compare the revision of
      unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA) with
      primary TKA through a review of previously published studies. The hypothesis was
      that the revised UKA group would need additional operative procedures, including
      the use of stems and augments, resulting in poorer clinical outcomes than those
      of the primary TKA group. METHODS: A literature search of online register
      databases was performed to identify clinical trials that compared revised UKA to
      TKA with primary TKA. An electronic literature search was performed using the
      Medline, Embase, Cochrane Library, Web of Science, and Scopus databases. No
      language or date restrictions were applied. RESULTS: A total of 2034 articles
      were identified from a keyword search, of which 11 studies were determined as
      eligible. They were all retrospective comparative studies. The revised UKA to TKA
      group had longer operation times resulting from additional procedures such as
      bone grafting and use of stems and augments, higher reoperation rates, and worse
      postoperative clinical outcomes based on the Western Ontario and McMaster
      Universities Osteoarthritis Index and Oxford Knee Score than the primary TKA
      group, with the differences being statistically significant. CONCLUSION: UKA
      should not be considered an alternative procedure to TKA. LEVEL OF EVIDENCE:
      Therapeutic Level III.

PMID- 29589050
TI  - Improved early outcome after TKA through an app-based active muscle training
      programme-a randomized-controlled trial.
AB  - PURPOSE: The purpose of this prospective randomized-controlled trial (RCT) was to
      evaluate if an app-based feedback-controlled active muscle training programme can
      be used to improve the outcome in the immediate postoperative period after total
      knee arthroplasty (TKA). METHODS: Sixty patients, with a median age of 65.9 years
      (range 45-84), awaiting primary TKA were randomized into a control and training
      group. Both groups followed an identical postoperative protocol. In addition, the
      training group postoperatively performed an app-based feedback-controlled active
      muscle training programme multiple times daily. Outcome measures were active and
      passive range of motion (ROM), pain at rest and in motion, knee extension
      strength, the timed "Up and Go", 10-m Walk Test, 30-s Chair Stand Test, Knee
      Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS), and
      clinical data. RESULTS: The training group performed an average of 18.4 training
      sessions, which led to significantly higher ROM, less pain at rest and in motion,
      higher strength, and significantly higher functional scores. More training
      correlated with a better outcome. CONCLUSIONS: The use of an app-based feedback
      controlled active muscle training programme can improve the clinical outcome
      after TKA, especially ROM and reduce pain. Clinically relevant is that the
      training programme could be considered an alternative to continuous passive
      motion after total knee arthroplasty. LEVEL OF EVIDENCE: II.

PMID- 29589051
TI  - [Chemotherapy-induced nausea and vomiting : Current recommendations for
      prophylaxis].
AB  - The chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent
      side effects in cytostatic therapy and a profound challenge during the therapy of
      cancer patients. Therefore, standardized guideline-orientated prophylaxis is
      essential and a fundamental contribution for the success of treatment. This
      review summarizes the current recommendations for CINV of the Multinational
      Association of Supportive Care in Cancer (MASCC) and European Society of Medical
      Oncology (ESMO), the American Society for Clinical Oncology (ASCO), the National
      Comprehensive Cancer Network (NCCN) and the S3-guideline Supportive Therapie of
      the Leitlinienprogramm Onkologie and shall facilitate its use in the daily
      routine.

PMID- 29589052
TI  - The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide dampens lipopolysaccharide
      induced transcriptomic changes in macrophages.
AB  - OBJECTIVE: M1-like inflammatory phenotype of macrophages plays a critical role in
      tissue damage in chronic inflammatory diseases. Previously, we found that the
      nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) dampens
      lipopolysaccharide (LPS)-triggered inflammatory priming of RAW 264.7 cells.
      Herein, we tested whether DMPO by itself can induce changes in macrophage
      transcriptome, and that these effects may prevent LPS-induced activation of
      macrophages. MATERIALS AND METHODS: To test our hypothesis, we performed a
      transcriptomic and bioinformatics analysis in RAW 264.7 cells incubated with or
      without LPS, in the presence or in the absence of DMPO. RESULTS: Functional data
      analysis showed 79 differentially expressed genes (DEGs) when comparing DMPO vs
      Control. We used DAVID databases for identifying enriched gene ontology terms and
      Ingenuity Pathway Analysis for functional analysis. Our data showed that DMPO vs
      Control comparison of DEGs is related to downregulation immune-system processes
      among others. Functional analysis indicated that interferon-response factor 7 and
      toll-like receptor were related (predicted inhibitions) to the observed
      transcriptomic effects of DMPO. Functional data analyses of the DMPO + LPS vs LPS
      DEGs were consistent with DMPO-dampening LPS-induced inflammatory transcriptomic
      profile in RAW 264.7. These changes were confirmed using Nanostring technology.
      CONCLUSIONS: Taking together our data, surprisingly, indicate that DMPO by itself
      affects gene expression related to regulation of immune system and that DMPO
      dampens LPS-triggered MyD88- and TRIF-dependent signaling pathways. Our research
      provides critical data for further studies on the possible use of DMPO as a
      structural platform for the design of novel mechanism-based anti-inflammatory
      drugs.

PMID- 29589053
TI  - Loss of Wilms tumor 1 protein is a marker for apoptosis in response to
      replicative stress in leukemic cells.
AB  - A remaining expression of the transcription factor Wilms tumor 1 (WT1) after
      cytotoxic chemotherapy indicates remaining leukemic clones in patients. We
      determined the regulation and relevance of WT1 in leukemic cells exposed to
      replicative stress and DNA damage. To induce these conditions, we used the
      clinically relevant chemotherapeutics hydroxyurea and doxorubicin. We
      additionally treated cells with the pro-apoptotic kinase inhibitor staurosporine.
      Our data show that these agents promote apoptosis to a variable extent in a panel
      of 12 leukemic cell lines and that caspases cleave WT1 during apoptosis. A
      chemical inhibition of caspases as well as an overexpression of mitochondrial,
      anti-apoptotic BCL2 family proteins significantly reduces the processing of WT1
      and cell death in hydroxyurea-sensitive acute promyelocytic leukemia cells.
      Although the reduction of WT1 correlates with the pharmacological efficiency of
      chemotherapeutics in various leukemic cells, the elimination of WT1 by different
      strategies of RNA interference (RNAi) does not lead to changes in the cell cycle
      of chronic myeloid leukemia K562 cells. RNAi against WT1 does also not increase
      the extent of apoptosis and the accumulation of gammaH2AX in K562 cells exposed
      to hydroxyurea. Likewise, a targeted genetic depletion of WT1 in primary oviduct
      cells does not increase the levels of gammaH2AX. Our findings position WT1 as a
      downstream target of the apoptotic process that occurs in response to cytotoxic
      forms of replicative stress and DNA damage.

PMID- 29589055
TI  - A walk after hemiplegia.

PMID- 29589054
TI  - Maintenance fluid therapy and fluid creep impose more significant fluid, sodium,
      and chloride burdens than resuscitation fluids in critically ill patients: a
      retrospective study in a tertiary mixed ICU population.
AB  - PURPOSE: Research on intravenous fluid therapy and its side effects, volume,
      sodium, and chloride overload, has focused almost exclusively on the
      resuscitation setting. We aimed to quantify all fluid sources in the ICU and
      assess fluid creep, the hidden and unintentional volume administered as a vehicle
      for medication or electrolytes. METHODS: We precisely recorded the volume,
      sodium, and chloride burdens imposed by every fluid source administered to 14,654
      patients during the cumulative 103,098 days they resided in our 45-bed tertiary
      ICU and simulated the impact of important strategic fluid choices on patients'
      chloride burdens. In septic patients, we assessed the impact of the different
      fluid sources on cumulative fluid balance, an established marker of morbidity.
      RESULTS: Maintenance and replacement fluids accounted for 24.7% of the mean daily
      total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were
      the most important sources of sodium and chloride. Fluid creep represented a
      striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308-1039
      mL)]. Chloride levels can be more effectively reduced by adopting a hypotonic
      maintenance strategy [a daily difference in chloride burden of 30.8 mmol (95% CI
      30.5-31.1)] than a balanced resuscitation strategy [daily difference 3.0 mmol
      (95% CI 2.9-3.1)]. In septic patients, non-resuscitation fluids had a larger
      absolute impact on cumulative fluid balance than did resuscitation fluids.
      CONCLUSIONS: Inadvertent daily volume, sodium, and chloride loading should be
      avoided when prescribing maintenance fluids in view of the vast amounts of fluid
      creep. This is especially important when adopting an isotonic maintenance
      strategy.

PMID- 29589057
TI  - Thomas L. Slovis (1941-2018).

PMID- 29589058
TI  - Combined prospectively electrocardiography- and respiratory-triggered sequential
      cardiac computed tomography in free-breathing children: success rate and image
      quality.
AB  - BACKGROUND: Combined prospectively electrocardiography (ECG)- and respiratory
      triggered sequential cardiac computed tomography (CT) has not been evaluated in
      free-breathing children. OBJECTIVE: To evaluate the success rate and image
      quality of combined prospectively ECG- and respiratory-triggered sequential
      cardiac CT in free-breathing children. MATERIALS AND METHODS: Image quality of
      combined prospectively ECG- and respiratory-triggered sequential cardiac CT in
      870 children (<=5 years of age) was evaluated in terms of severe motion (maximal
      distance >=2 mm) and band artifacts (maximal attenuation difference >=100
      Hounsfield units). The success rate of the scan mode was calculated. The causes
      of failed cases were assessed. Patient-related, radiation and image quality
      parameters were compared between success and failure groups. RESULTS: Severe
      motion artifacts were observed in 10.6% (92/870) of patients due to cardiac phase
      error in 17 (18.5%), patient motion in 12 (13.0%), and unknown causes in 63
      (68.5%). Severe band artifacts were seen in 13.2% (115/870) of patients. Combined
      prospectively ECG- and respiratory-triggered sequential cardiac CT was
      successfully performed in 78.5% (683/870) of patients, while it failed in 21.5%
      (187/870). All the evaluated patient-related, radiation and image quality
      parameters were significantly different (P<=0.001) between success and failure
      groups except effective dose (P>0.05). CONCLUSION: Additional prospective
      respiratory triggering can reduce motion artifacts in prospectively ECG-triggered
      sequential cardiac CT in free-breathing children.

PMID- 29589059
TI  - Cinematic rendering of small bowel pathology: preliminary observations from this
      novel 3D CT visualization method.
AB  - 3D visualization methods for volumetric CT data have played an important role in
      diagnostic imaging of the small bowel, a structure which intrinsically crosses
      numerous slices in any 2D imaging plane. Recently, a new approach to 3D CT image
      creation has become available-cinematic rendering (CR). CR differs from other 3D
      methods in making use of a global lighting model that produces high surface
      detail and realistic shadowing effects that lead to 3D visualizations with
      photorealistic quality. Although the utility of these images for improving
      diagnostic accuracy has not yet been established, our group's early experience in
      regions of complex anatomy and pathology has been encouraging. In this pictorial
      review, we review the established role of 3D CT in many of the most common small
      bowel pathologies, provide examples of those pathologies visualized with CR, and
      suggest future directions for researchers to pursue.

PMID- 29589061
TI  - Overview of Osteoimmunology.
AB  - Aberrant or prolonged immune responses often affect bone metabolism. The
      investigation on bone destruction observed in autoimmune arthritis contributed to
      the development of research area on effect of the immune system on bone. A number
      of reports on bone phenotypes of immunocompromised mice indicate that the immune
      and skeletal systems share various molecules, including transcription factors,
      signaling molecules, and membrane receptors, suggesting the interplay between the
      two systems. Furthermore, much attention has been paid to the modulation of
      immune cells, including hematopoietic progenitor cells, by bone cells in the bone
      marrow. Thus, osteoimmunology which deals with the crosstalk and shared
      mechanisms of the bone and immune systems became the conceptual framework
      fundamental to a proper understanding of both systems and the development of new
      therapeutic strategies.

PMID- 29589060
TI  - Associations Between Objectively Measured Physical Activity, Body Composition and
      Sarcopenia: Findings from the Hertfordshire Sarcopenia Study (HSS).
AB  - Regular physical activity (PA) is associated with reduced risk of the development
      and progression of musculoskeletal, metabolic and vascular disease. However, PA
      declines with age and this can contribute to multiple adverse outcomes. The aims
      of this study were to describe the relationship between accelerometer-determined
      PA, body composition and sarcopenia (the loss of muscle mass and function with
      age). Seven-day PA was measured using the GENEactiv accelerometer among 32 men
      and 99 women aged 74-84 years who participated in the Hertfordshire Sarcopenia
      Study. We measured mean daily acceleration and minutes/day spent in non-sedentary
      and moderate-to-vigorous physical activity (MVPA) levels. Body composition was
      measured by dual-energy X-ray absorptiometry, muscle strength by grip dynamometry
      and function by gait speed. Sarcopenia was defined according to the EWGSOP
      diagnostic algorithm. Men and women spent a median (inter-quartile range) of
      138.8 (82, 217) and 186 (122, 240) minutes/day engaging in non-sedentary activity
      but only 14.3 (1.8, 30.2) and 9.5 (2.1, 18.6) min in MVPA, respectively. Higher
      levels of PA were associated with reduced adiposity, faster walking speed and
      decreased risk of sarcopenia. For example, a standard deviation (SD) increase in
      mean daily acceleration was associated with an increase in walking speed of 0.25
      (95% CI 0.05, 0.45) SDs and a reduction in the risk of sarcopenia of 35% (95% CI
      1, 57%) in fully adjusted analyses. PA was not associated with hand grip
      strength. Community-dwelling older adults in this study were largely sedentary
      but there was evidence that higher levels of activity were associated with
      reduced adiposity and improved function. PA at all intensity levels in later life
      may help maintain physical function and protect against sarcopenia.

PMID- 29589062
TI  - N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment
      interaction in Ethiopians.
AB  - BACKGROUND AND OBJECTIVES: N-acetyltransferase 2 (NAT2) metabolize several drugs
      including isoniazid. We investigated the effect of genotype, geographical
      difference, and smoking habit on NAT2 phenotype in Ethiopians. METHODS:
      Genotyping for NAT2 191G > A, 341 T > C, 590G > A, and 857G > A was performed in
      163 unrelated healthy Ethiopians (85 living in Ethiopia and 78 living in Sweden).
      The NAT2 phenotype was determined using caffeine as a probe and log AFMU/(AFMU +
      1X + 1 U) urinary metabolic ratio (MR) as an index. RESULTS: The frequencies of
      NAT2*4, *5, *6, *7, and *14 haplotypes were 14.1, 48.5, 30.1, 5.5, and 1.8%,
      respectively. The frequencies of rapid (NAT2*4/*4), intermediate (heterozygous
      *4), and slow (no *4 allele) acetylator genotypes were 1.8, 24.6, and 73.6%,
      respectively. The distribution NAT2 MR was bimodal with 70% being phenotypically
      slow acetylators. NAT2 genotype (p < 0.0001) and country of residence (p = 0.004)
      independently predicted NAT2 phenotype. Controlling for the effect of genotype,
      ethnic Ethiopians living in Ethiopia had significantly higher NAT2 MR than those
      living in Sweden (p = 0.006). NAT2 genotype-phenotype concordance rate was 75%.
      Distinct country-of-residence-based genotype-phenotype discordance was observed.
      The proportion of phenotypically determined rapid acetylators was significantly
      higher and slow acetylators was lower in Ethiopians living in Ethiopia (39%
      rapid, 61% slow) than in Sweden (20% rapid, 80% slow). Sex and smoking had no
      significant effect on NAT2 MR. CONCLUSIONS: We report a high prevalence of NAT 2
      slow acetylators in Ethiopians and a conditional NAT2 genotype-phenotype
      discordance implicating a partial phenotype conversion and metabolic adaptation.
      Gene-environment interactions regulate NAT2 phenotype.

PMID- 29589063
TI  - Patterns of direct oral anticoagulant drug prescription in France in 2010-2013: a
      study in the Midi-Pyrenees area.
AB  - AIM: The aim of our study was to study the pattern of prescription of direct
      acting oral anticoagulants (DOACs) according to the French recommendations.
      METHODS: We performed a cross-sectional study using anonymous data of patients
      covered by the French National Health Insurance information system (SNIIRAM) from
      1 January 2010 to 31 December 2013 in the area of Midi-Pyrenees (southwest of
      France). RESULTS: Of the 355,608 patients identified, 325,216 (91.5%) were
      included, of whom 22,142 received at least one DOAC. About 39.1% (8,652 patients)
      had DOAC in an orthopedic indication, 46.5% (10,303 patients) in a cardiac
      indication, and 16.1% (3568 patients) in an indeterminate indication. Overall,
      guidelines were largely followed as for renal function monitoring, prescribing in
      orthopedic indications, in cardiac indications in patients aged 80 years and
      older, and in the case of concomitant use of verapamil. However, inappropriate
      prescriptions were observed for cardiac indications, and for dosage adjustments
      in orthopedic indications, with respect to both the age of patients (75 years and
      older) and those taking verapamil or amiodarone concomitantly. Guidelines were
      more followed in women and patients aged 80 or more. CONCLUSIONS: Among patients
      receiving DOACs, 58% were exposed to a prescription falling outside the
      guidelines. This study on DOAC prescription patterns revealed insufficiencies in
      the compliance with the French guidelines in certain indications.

PMID- 29589064
TI  - Recent major advances in cardiovascular pharmacotherapy.
AB  - The field of cardiovascular pharmacotherapy remains extremely active. The aim of
      this review is to summarize the recent major advances in cardiovascular
      pharmacotherapy, with a focus on (1) the new approved drug for treatment of heart
      failure with reduced ejection fraction-sacubitril/valsartan; (2) proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors; (3) the novel reversal
      agents for non-vitamin K oral anticoagulants (NOACs); and finally, (4) new
      evidence on pharmacological treatment of coronary artery disease.

PMID- 29589065
TI  - Relationship between frailty, polypharmacy, and underprescription in older adults
      living in nursing homes.
AB  - PURPOSE: Frailty, polypharmacy, and underprescription are considered a major
      matter of concern in nursing homes, but the possible relationships between them
      are not well known. The aim is to examine the possible association between
      medication underprescription, polypharmacy, and frailty in older people living in
      nursing homes. METHODS: A cross-sectional analysis from a concurrent cohort
      study, including 110 subjects >= 65 years living in two nursing homes. Four
      frailty scales were applied; polypharmacy was defined as >= 5 medications and
      underprescription was measured with Screening Tool to Alert to Right Treatment
      (START) criteria. Logistic regression models were performed to assess the
      associations. RESULTS: The mean age was 86.3 years (SD 7.3) and 71.8% were
      female. 73.6% of subjects took >= 5 chronic medications and 60.9% met one or more
      START criteria. The non-frail participants took more medications than the frail
      subjects according to the imputated frailty Fried criteria (8.1 vs 6.7, p =
      0.042) and the FRAIL-NH scale (7.8 vs 6.8, p = 0.026). Multivariate analyses did
      not find an association between frailty and polypharmacy. Frail participants
      according to the Fried criteria met a higher number of START criteria (1.9 vs
      1.0, p = 0.017), and had a higher prevalence of underprescription (87.5 vs
      50.0%), reaching the limit of statistical significance in multivariate analysis.
      CONCLUSION: The positive association found in previous studies between frailty
      and polypharmacy cannot be extrapolated to institutionalized populations. There
      is a trend towards higher rates of underprescription in frail subjects.
      Underprescription in frail older adults should be redefined and new strategies to
      measure it should be developed.

PMID- 29589067
TI  - Clozapine-related neutropenia, myocarditis and cardiomyopathy adverse event
      reports in Australia 1993-2014.
AB  - RATIONALE: Clozapine is the gold-standard medicine for treating refractory
      schizophrenia but there are some notable serious adverse events (AE). We aimed to
      analyse reported rates of clozapine cardiac and haematological AEs in Australia.
      METHODS: Using data from the Therapeutic Goods Administration, we examined all
      reported clozapine AEs (1993-2014) with a specific focus on neutropenia,
      myocarditis and cardiomyopathy. We related AEs to clozapine-dispensing data in
      Queensland, scaled up to Australia. RESULTS: There were 8561 AEs reported:
      neutropenia (13.7%), myocarditis (9.3%) and cardiomyopathy (3.8%). Reported rates
      of myocarditis and cardiomyopathy increased after 1999 following a myocarditis
      case series from Sydney. Cardiomyopathy AE rates have remained stable since then
      but myocarditis AEs have increased steadily. Neutropenia was more common in
      women, while cardiomyopathy and myocarditis were more common in men. There were
      five reported deaths from neutropenia and cardiomyopathy. CONCLUSIONS: The rates
      of serious AEs (including deaths) are low and likely an underestimate of true
      rates and need to be considered by clinicians in balancing the risks and
      benefits. Continued education on the monitoring and treatment of these AEs for
      consumers, carers and health professionals is essential and reporting these to
      the relevant national reporting agency is crucial.

PMID- 29589066
TI  - Potentially inappropriate medication in the elderly: a systematic review of
      validated explicit criteria.
AB  - PURPOSE: Potentially inappropriate medication (PIM) use causes preventable
      adverse drug reactions in older patients. Several assessment tools have been
      published to identify and avoid PIM use. In this systematic literature review, we
      aim to provide summaries and comparisons of validated PIMs lists published
      between 1991 and 2017 internationally. METHODS: In accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), we
      performed a systematic review of articles describing the development and
      validation of criteria for identification of PIMs among older people published
      between January 1991 and April 2017. The searches were conducted on PUBMED,
      AgeLine, Academic Search, Academic Search Premier, and CINAHL. We identified the
      most common medications/classes described as PIM. We also identified the drug
      disease interactions and drug-drug interactions reported among criteria. RESULTS:
      From 2933 articles screened, 36 met our inclusion criteria. The majority used the
      Delphi method to validate their criteria. We identified 907 different
      medications/classes, 536 different drug disease interactions involving 84
      diseases/conditions, and 159 drug-drug interactions. Benzodiazepines and
      nonsteroidal anti-inflammatory drugs were the medications most commonly reported
      as potentially inappropriate for older people. CONCLUSION: Although approaches
      aimed at detecting inappropriate prescribing have intensified in recent years, we
      observed limited overlap between different PIM lists. Additionally, some PIM
      lists did not provide special considerations of use and alternative therapies to
      avoid PIMs. These facts may compromise the use of PIM lists in clinical practice.
      Future PIM lists should integrate information about alternative therapies and
      special considerations of use in order to help clinicians in the drug
      prescription.

PMID- 29589068
TI  - A history of binge drinking during adolescence is associated with poorer sleep
      quality in young adult Mexican Americans and American Indians.
AB  - RATIONALE: Binge drinking during adolescence is common, and adolescents and young
      adults with alcohol problems may also have sleep difficulties. However, few
      studies have documented the effects of a history of adolescent binge drinking on
      sleep in young adulthood in high-risk minority populations. OBJECTIVES: To
      quantify sleep disturbance, as indexed by the Pittsburgh Sleep Quality Index
      (PSQI), in a sample of young adult Mexican American and American Indian men and
      women (18-30 years, n = 800) with and without a history of alcohol binge drinking
      during adolescence, controlling for age, gender, and race. RESULTS: Gender was
      found to affect PSQI responses with females reporting waking up at night, having
      more bad dreams, and later habitual bedtimes than males, and males reporting more
      problems with breathing and snoring. Increasing age was associated with snoring
      or coughing, less hours spent in bed, and later evening bedtimes. Race also
      influenced the PSQI with American Indians reporting longer sleep latencies and
      sleep durations, more hours spent in bed, and more trouble with coughing and
      snoring than Mexican Americans, and Mexican Americans reporting later bedtimes. A
      history of adolescent regular binge drinking was associated with longer sleep
      latencies, more problems with breathing, bad dreams, and an overall higher PSQI
      total score, when controlling for age, race, and gender. CONCLUSIONS: This report
      suggests, like what has been found in young adults in general population samples,
      that binge drinking during adolescence is associated with deleterious
      consequences on sleep quality in young adulthood in these high-risk and
      understudied ethnic groups.

PMID- 29589069
TI  - Effect of gabapentin on sleep and delta and theta EEG power in adult rats exposed
      to chronic intermittent ethanol vapor and protracted withdrawal during
      adolescence.
AB  - RATIONALE: Adolescents and young adults with alcohol problems may also have sleep
      difficulties. However, whether these sleep problems are a result of a history of
      drinking or arise due to other comorbid disorders is difficult to disentangle in
      human studies. Additionally, the mechanisms underlying adolescent alcohol-induced
      sleep disturbances and potential targets for therapy also remain under
      investigated. Recent clinical trials have demonstrated that the anticonvulsant
      and analgesic drug gabapentin may have therapeutic value in normalizing sleep
      quality in adult recovering alcoholics, yet its potential for the treatment of
      adolescent sleep disturbances has not been investigated. OBJECTIVES: This study
      sought to evaluate the effects of a history of 5 weeks of chronic intermittent
      ethanol vapor exposure, administered during adolescence (AIE), on EEG sleep, in
      young adult rats (n = 29). The ability of two doses of gabapentin (30, 120 mg/kg)
      to modify sleep and slow wave activity were also investigated in these young
      adult rats exposed to alcohol vapor during adolescence. RESULTS: Adolescent vapor
      exposure in the rat was found to result in deficits in delta (1-4 Hz) and theta
      (4-8 Hz) power during slow wave sleep. Administration of gabapentin caused a
      "normalization" of the delta power deficits but did not affect theta power.
      CONCLUSIONS: This report suggests that the potential mechanisms and therapeutic
      targets for sleep disturbance associated with adolescent alcohol exposure can be
      studied in preclinical models and that gabapentin may show partial efficacy in
      ameliorating these sleep deficits.

PMID- 29589070
TI  - Vitamin A-coupled liposomes carrying TLR4-silencing shRNA induce apoptosis of
      pancreatic stellate cells and resolution of pancreatic fibrosis.
AB  - : Chronic pancreatitis leads to irreversible damage in pancreatic endocrine and
      exocrine functions. However, there is no clinically available antifibrotic drug.
      Pancreatic stellate cells (PSCs) can be activated by Toll-like receptor 4 (TLR4)
      responses to its ligands and they contribute to the formation of pancreatic
      fibrosis. Silencing the expression of TLR4 in PSCs by RNAi may be a novel
      therapeutic strategy for the treatment of pancreatic fibrosis. In addition, PSCs
      have a remarkable capacity for vitamin A uptake most likely through cellular
      retinol binding protein (CRBP). In our study, to ensure the efficient delivery of
      RNAi therapeutic agents to PSCs, VitA-coupled liposomes (VA-lips) were used as
      drug carriers to deliver plasmids expressing TLR4-specific short hairpin RNA
      (shRNA) to treat pancreatic fibrosis. Our study demonstrated that silencing the
      expression of TLR4 could induce mitochondrial apoptosis in aPSCs and might be an
      effective therapeutic strategy for the treatment of pancreatic fibrosis. KEY
      MESSAGES: VA-lip-shRNA-TLR4 recovers pancreatic tissue damage. VA-lip-shRNA-TLR4
      resolution of pancreatic fibrosis. VA-lip-shRNA-TLR4 accelerates ECM degradation
      and inhibits ECM synthesis. Silencing TLR4 induces aPSCs mitochondrial apoptosis.
      Silencing TLR4 inhibits the activation of NF-kappaB.

PMID- 29589071
TI  - Distribution of IL-1beta immunoreactive cells in pancreatic biopsies from living
      volunteers with new-onset type 1 diabetes: comparison with donors without
      diabetes and with longer duration of disease.
AB  - AIMS/HYPOTHESIS: Although IL-1beta is considered a key mediator of beta cell
      destruction, its cellular expression in islets during early type 1 diabetes
      remains unclear. We compared its expression in rare pancreatic biopsies from new
      onset living volunteers with its expression in cadaveric pancreas sections from
      non-diabetic autoantibody-positive and -negative individuals and those with long
      standing disease. METHODS: Pancreatic biopsy sections from six new-onset living
      volunteers (group 1) and cadaveric sections from 13 non-diabetic autoantibody
      negative donors (group 2), four non-diabetic autoantibody-positive donors (group
      3) and nine donors with diabetes of longer duration (0.25-12 years of disease;
      group 4) were triple-immunostained for IL-1beta, insulin and glucagon. Intra- and
      peri-islet IL-1beta-positive cells in insulin-positive and -negative islets and
      in random exocrine fields were enumerated. RESULTS: The mean number of IL-1beta
      positive cells per islet from each donor in peri- and intra-islet regions was
      <1.25 and <0.5, respectively. In all study groups, the percentage of islets with
      IL-1beta cells in peri- and/or intra-islet regions was highly variable and ranged
      from 4.48% to 17.59% in group 1, 1.42% to 44.26% in group 2, 7.93% to 17.53% in
      group 3 and 3.85% to 42.86% in group 4, except in a single case where the value
      was 75%. In 25/32 donors, a higher percentage of islets showed IL-1beta-positive
      cells in peri-islet than in intra-islet regions. In sections from diabetic donors
      (groups 1 and 4), a higher mean number of IL-1beta-positive cells occurred in
      insulin-positive islets than in insulin-negative islets. In group 2, 70-90% of
      islets in 3/13 sections had weak-to-moderate IL-1beta staining in alpha cells but
      staining was virtually absent or substantially reduced in the remaining groups.
      The mean number of exocrine IL-1beta-positive cells in group 1 was lower than in
      the other groups. CONCLUSIONS/INTERPRETATION: At onset of type 1 diabetes, the
      low number of islet-associated IL-1beta-positive cells may be insufficient to
      elicit beta cell destruction. The variable expression in alpha cells in groups 2
      4 suggests their cellular heterogeneity and probable physiological role. The
      significance of a higher but variable number of exocrine IL-1beta-positive cells
      seen in non-diabetic individuals and those with long-term type 1 diabetes remains
      unclear.

PMID- 29589072
TI  - The resident macrophages in murine pancreatic islets are constantly probing their
      local environment, capturing beta cell granules and blood particles.
AB  - AIMS/HYPOTHESIS: We studied here the interactions between the resident
      macrophages of pancreatic islets with beta cells and the blood vasculature. We
      also examined the immunological consequences of such interactions. METHODS:
      Islets were isolated from C57BL/6 mice expressing CX3C motif chemokine receptor 1
      green fluorescent protein (CX3CR-GFP) and examined live by two-photon microscopy.
      Islets were also examined by electron microscopy to study the relationship of the
      intra-islet macrophages with the beta cells. In NOD.Rag1-/- mice and young (non
      diabetic) male mice, the acquisition of beta cell granules was tested
      functionally by probing with CD4+ T cells directed against insulin epitopes.
      RESULTS: Two-photon microscopy showed that the islet resident macrophages were in
      close contact with blood vessels and had extensive filopodial activity. Some
      filopodia had direct access to the vessel lumen and captured microparticles.
      Addition of glucose at high concentration reduced the degree of filopodia
      sampling of islets. This finding applied to in vivo injection of glucose or to in
      vitro cultures. Ultrastructural examination showed the close contacts of
      macrophages with beta cells. Such macrophages contained intact dense core
      granules. Functional studies in NOD mice indicated that the macrophages presented
      insulin peptides to insulin-reactive T cells. Presentation was increased after
      glucose challenge either ex vivo or after an in vivo pulse. In agreement with the
      morphological findings, presentation was not affected by insulin receptor
      blockade. CONCLUSIONS/INTERPRETATION: Islet resident macrophages are highly
      active, sampling large areas of the islets and blood contents and capturing beta
      cell granules. After such interactions, macrophages present immunogenic insulin
      to specific autoreactive T cells.

PMID- 29589074
TI  - [Development of a risk score to predict postoperative biliary leakage after
      partial liver resection].

PMID- 29589073
TI  - Overweight, obesity and the risk of LADA: results from a Swedish case-control
      study and the Norwegian HUNT Study.
AB  - AIMS/HYPOTHESIS: Excessive weight is a risk factor for type 2 diabetes, but its
      role in the promotion of autoimmune diabetes is not clear. We investigated the
      risk of latent autoimmune diabetes in adults (LADA) in relation to
      overweight/obesity in two large population-based studies. METHODS: Analyses were
      based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and
      1704 randomly selected control participants from a Swedish case-control study and
      prospective data from the Norwegian HUNT Study including 147 people with LADA and
      1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs
      with 95% CI. RESULTS: In the Swedish data, obesity was associated with an
      increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for
      type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in
      LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but
      present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish
      data, obese vs normal weight LADA patients had lower GADA levels, better beta
      cell function, and were more likely to have low-risk HLA-genotypes. The
      combination of overweight and family history of diabetes (FHD) conferred an OR of
      4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2
      diabetes. Prospective data from HUNT indicated even stronger associations; HR for
      LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for
      overweight and FHD. CONCLUSIONS/INTERPRETATION: Overweight/obesity is associated
      with increased risk of LADA, particularly when in combination with FHD. These
      findings support the hypothesis that, even in the presence of autoimmunity,
      factors linked to insulin resistance, such as excessive weight, could promote
      onset of diabetes.

PMID- 29589075
TI  - [Operative treatment of diabetics with vascular complications : Secondary data
      analysis of diagnosis-related groups statistics from 2005 to 2014 in Germany].
AB  - BACKGROUND: In Germany approximately 40,000 amputations per year are performed on
      patients with diabetes mellitus, often with accompanying vascular complications.
      OBJECTIVE: The aim of this study was to present the various degrees of severity
      of the vascular complications and the temporal changes of the treatment options
      in diabetics with vascular complications in Germany. MATERIAL AND METHODS: The
      microdata of the diagnosis-related groups (DRG) statistics of the Federal
      Statistical Office were analyzed over the period from 2005 to 2014. All cases
      were included in which the main or secondary diagnosis of diabetes mellitus with
      concurrent vascular complications (diabetic angiopathy and peripheral arterial
      disease) was encrypted. RESULTS: The median age of the 1,811,422 cases was 73
      years and 62% were male. While the total number of amputations remained stable
      over time, there was a 41% reduction in knee-preserving and a 31% reduction in
      non-knee preserving major amputations with an 18% increase in minor amputations.
      Revascularization increased by 33% from 36 procedures in 2005 to 48 procedures
      per 100,000 inhabitants. The increase in revascularization was evident in the
      area of endovascular therapy alone where there was an increase of 78%.
      CONCLUSION: Due to the significant increase in endovascular revascularization
      measures, there was a significant increase in the proportion of diabetes patients
      with vascular pathologies in whom revascularization was carried out. As a result,
      improved limb preservation was achieved despite equally high amputation rates due
      to increasing minor amputation rates.

PMID- 29589076
TI  - [Robot-assisted vs laparoscopic gastric bypass : First experiences with the
      DaVinci system in bariatric surgery].
AB  - Conventional laparoscopy is the gold standard in bariatric surgery.
      Internationally, robot-assisted surgery is gaining in importance. Up to now there
      are only few reports from Germany on the use of the system in bariatric surgery.
      Since January 2017 we have been performing robot-assisted gastric bypass surgery.
      It remains unclear whether the use of the robotic system has advantages over the
      well-established laparoscopic technique. Within a period from January to early
      August 2017 a total of 53 gastric bypass operations were performed. Of these 16
      proximal redo Roux-en-Y gastric bypass operations were performed with the DaVinci
      Si system versus 29 laparoscopic procedures. A retrospective analysis of the
      perioperative course was carried out. Body weight, body mass index (BMI),
      Edmonton obesity staging system (EOSS) and American Society of Anesthesiologists
      (ASA) classification did not show significant differences. There were also no
      significant differences in terms of estimated blood loss, intraoperative
      complications, duration of surgery, postoperative inflammatory parameters and
      weight loss. There was no mortality and no need for revisional surgery in either
      group. After laparoscopic surgery there was a delayed occurrence of a leak of the
      gastrojejunostomy followed by readmission and endoscopic negative pressure wound
      therapy. The results show that the proximal Roux-en-Y gastric bypass can be
      performed safely and efficiently using the DaVinci surgical system. Significant
      differences to the conventional laparoscopic procedure were not found. Larger
      randomized controlled trials are needed to define the role of the DaVinci system
      in bariatric surgery.

PMID- 29589077
TI  - [Surgical treatment of peritoneal metastases of colorectal cancer].
AB  - Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      may significantly improve overall survival in selected patients with peritoneal
      metastases of colorectal cancer. For good oncological results complete
      macroscopic cytoreduction is crucial; furthermore, a linear correlation between
      peritoneal tumor load, as determined by the peritoneal cancer index (PCI) and
      overall survival has been demonstrated; therefore, surgical treatment should be
      initiated as early as possible. Synchronous resection of up to three liver
      metastases may be performed safely and with good results and no influence on the
      morbidity. With respect to intraperitoneal chemotherapy, mitomycin C and
      oxaliplatin are most commonly used and may be regarded as equal; however, for
      perioperative chemotherapy study results are so far inconclusive with some trials
      hinting at decreased overall survival following neoadjuvant chemotherapy.
      Adjuvant therapy is likely to improve overall survival if at least 6 cycles are
      applied. Early detection of peritoneal metastases is difficult at present but
      might be facilitated in the future by the use of liquid biopsies, which may
      detect circulating free tumor-specific DNA or RNA. In the meantime, planned
      second-look laparotomy should be considered for patients at high risk of
      peritoneal recurrence. In addition, several international studies are currently
      evaluating the concept of adjuvant or prophylactic HIPEC. The CRS and HIPEC may
      be repeated in cases of recurrence and should be considered in suitable patients,
      applying the same criteria as for primary CRS and HIPEC. A recurrence-free
      interval of >2 years is associated with a significantly better prognosis.

PMID- 29589078
TI  - Effects of a cognitive dual task on variability and local dynamic stability in
      sustained repetitive arm movements using principal component analysis: a pilot
      study.
AB  - In many daily jobs, repetitive arm movements are performed for extended periods
      of time under continuous cognitive demands. Even highly monotonous tasks exhibit
      an inherent motor variability and subtle fluctuations in movement stability.
      Variability and stability are different aspects of system dynamics, whose
      magnitude may be further affected by a cognitive load. Thus, the aim of the study
      was to explore and compare the effects of a cognitive dual task on the
      variability and local dynamic stability in a repetitive bimanual task. Thirteen
      healthy volunteers performed the repetitive motor task with and without a
      concurrent cognitive task of counting aloud backwards in multiples of three.
      Upper-body 3D kinematics were collected and postural reconfigurations-the
      variability related to the volunteer's postural change-were determined through a
      principal component analysis-based procedure. Subsequently, the most salient
      component was selected for the analysis of (1) cycle-to-cycle spatial and
      temporal variability, and (2) local dynamic stability as reflected by the largest
      Lyapunov exponent. Finally, end-point variability was evaluated as a control
      measure. The dual cognitive task proved to increase the temporal variability and
      reduce the local dynamic stability, marginally decrease endpoint variability, and
      substantially lower the incidence of postural reconfigurations. Particularly, the
      latter effect is considered to be relevant for the prevention of work-related
      musculoskeletal disorders since reduced variability in sustained repetitive tasks
      might increase the risk of overuse injuries.

PMID- 29589079
TI  - Kinematics of ventrally mediated grasp-to-eat actions: right-hand advantage is
      dependent on dorsal stream input.
AB  - Studies have suggested a left-hemisphere specialization for visually guided grasp
      to-eat actions by way of task-dependent kinematic asymmetries (i.e., smaller
      maximum grip apertures for right-handed grasp-to-eat movements than for right
      handed grasp-to-place movements or left-handed movements of either type). It is
      unknown, however, whether this left-hemisphere/right-hand kinematic advantage is
      reliant on the dorsal "vision-for-action" visual stream. The present study
      investigates the kinematic differences between grasp-to-eat and grasp-to place
      actions performance during closed-loop (i.e., dorsally mediated) and open-loop
      delay (i.e., ventrally mediated) conditions. Twenty-one right-handed adult
      participants were asked to reach to grasp small food items to (1) eat them, or
      (2) place them in a container below the mouth. Grasps were performed in both
      closed-loop and open-loop delay conditions, in separate sessions. We show that
      participants displayed the right-hand grasp-to-eat kinematic advantage in the
      closed-loop condition, but not in the open-loop delay condition. As no task
      dependent kinematic differences were found in ventrally mediated grasps, we posit
      that the left-hemisphere/right-hand advantage is dependent on dorsal stream
      processing.

PMID- 29589080
TI  - Postural time-to-contact as a precursor of visually induced motion sickness.
AB  - The postural instability theory of motion sickness predicts that subjective
      symptoms of motion sickness will be preceded by unstable control of posture. In
      previous studies, this prediction has been confirmed with measures of the spatial
      magnitude and the temporal dynamics of postural activity. In the present study,
      we examine whether precursors of visually induced motion sickness might exist in
      postural time-to-contact, a measure of postural activity that is related to the
      risk of falling. Standing participants were exposed to oscillating visual motion
      stimuli in a standard laboratory protocol. Both before and during exposure to
      visual motion stimuli, we monitored the kinematics of the body's center of
      pressure. We predicted that postural activity would differ between participants
      who reported motion sickness and those who did not, and that these differences
      would exist before participants experienced subjective symptoms of motion
      sickness. During exposure to visual motion stimuli, the multifractality of sway
      differed between the Well and Sick groups. Postural time-to-contact differed
      between the Well and Sick groups during exposure to visual motion stimuli, but
      also before exposure to any motion stimuli. The results provide a qualitatively
      new type of support for the postural instability theory of motion sickness.

PMID- 29589084
TI  - Soft tissue tension is four times lower in the unstable primary total hip
      arthroplasty.
AB  - PURPOSE: The aim was to compare patients who suffered recurrent dislocation
      following total hip arthroplasty (THA) with those who did not to clarify the
      degree of soft tissue tension in dislocation patients. METHODS: The subjects were
      18 hips with recurrent dislocation (unstable THA group) and 37 hips without
      dislocation (stable THA group). To evaluate soft tissue tension, radiographs were
      taken while applying distal traction at traction forces of 40, 30, and 20% of the
      body weight (BW) and femoral head displacement was measured. Acetabular offset,
      femoral offset, limb offset, and leg length discrepancy were measured in patients
      with a normal contralateral hip joint. RESULTS: The mean femoral head
      displacement in the unstable THA group was 5.6 mm at 40% of the BW, 4.6 mm at 30%
      of the BW, and 3.5 mm at 20% of the BW. In the stable THA group, the mean femoral
      head displacement was 1.4 mm at 40% of the BW, 1.1 mm at 30% of the BW, and 0.9
      mm at 20% of the BW. Significant differences were seen between the groups at all
      traction forces. Furthermore, on comparing the unstable and stable THA groups,
      femoral offset was found to significantly be smaller in the affected side than in
      the healthy side in the unstable THA group. CONCLUSIONS: We found that soft
      tissue tension is approximately fourfold lower in patients exhibiting recurrent
      dislocations following THA than in patients exhibiting no dislocations and that
      femoral offset was related to decreased soft tissue tension.

PMID- 29589085
TI  - Real-time computerised tomography assisted porous tantalum implant in ARCO stage
      I-II non-traumatic osteonecrosis of the femoral head: minimum five-year follow
      up.
AB  - PURPOSES: This study was established to investigate the medium-term clinical
      effect of real-time CT assisted porous tantalum implant for the treatment of ARCO
      stage I-II non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: This
      study comprised 24 ONFH patients (29 hips) who were treated with intra-operative
      real-time CT accurate rapid positioning assisted drilling decompression, lesion
      removal and porous tantalum implant. Harris score, VAS score and imaging in pre
      operation and follow-up period were recorded. RESULTS: The average operative time
      and intra-operative blood loss were 72.6 min and 158.8 ml, respectively. The mean
      follow-up was 5.4 years. No femoral head penetrating, wound infection, and death
      occurred. Harris and VAS score improved significantly (73.78 vs. 88.11; 7.13 vs.
      2.66) at last follow-up (P < 0.05). The functional improvement and pain relief
      rate was 100% at six months after operation. The effective rate was 86.21% at 12
      months after operation and last follow-up. Five pre-operative ARCO stage I hips
      had no radiographic progress. Meanwhile, four among the 24 ARCO stage II hips
      progressed into stage III between eight and 12 months after surgery, among which
      two progressed into stage IV and two remained in stage III at the last follow-up.
      The average value of Kerboul combined necrotic angle was 263.24 degrees . There
      was no progress in Kerboul combined necrotic angle among the grades 2 and 3
      patients. However, among the six cases at grade 4, four cases with post-operative
      progress, two patients converted to THA. CONCLUSIONS: Our technique is safety and
      effective in the treatment of ARCO stage I-II non-traumatic ONFH.

PMID- 29589086
TI  - Subchondral stem cell therapy versus contralateral total knee arthroplasty for
      osteoarthritis following secondary osteonecrosis of the knee.
AB  - PURPOSE: Total knee arthroplasty (TKA) implanted in patients with secondary
      osteonecrosis (ON) related to corticosteroids have relatively poor outcome (20%
      revision rate) at a mean follow-up of only eight years. With the hypothesis that
      subchondral bone marrow injection might improve knees in these patients, we
      evaluated 30 patients who had bilateral knee osteoarthritis with severe joint
      space narrowing and received TKA in one knee and subchondral bone marrow
      concentrate injection in the contralateral knee. MATERIAL AND METHODS: A
      prospective randomized controlled clinical trial was carried out in 60 knees of
      30 patients (mean age 28 years, 18-41) who presented bilateral osteoarthritis
      secondary to knee ON related to corticosteroids in relation with different severe
      medical conditions. During the same anesthesia, one knee received TKA; for the
      other knee, a bone marrow graft containing an average of 6500 MSCs/mL (counted as
      CFU-F, range 3420 to 9830) was delivered to the subchondral bone of the femur and
      tibia. The length of anesthesia related to each procedure (bone marrow aspiration
      and subchondral injection of concentrated bone marrow versus total knee
      arthroplasty) was measured. Peri-operative outcomes, morbidity, complications,
      and safety of the two procedures were compared. Subsequent admissions for
      revision surgery were identified. At the most recent follow-up (average of 12
      years, range 8 to 16 years), clinical outcomes of the patient (Knee Society
      score) were obtained along with radiological imaging outcomes (MRIs for knees
      with subchondral bone marrow injection). RESULTS: Anesthesia related to the TKA
      side was longer than for the cell therapy group. Medical and surgical
      complications were more frequent after TKA. A higher number of thrombophlebitis
      was observed on the side with TKA (15%) versus none on the side with cell therapy
      (0%). At the most recent follow-up (average of 12 years, range 8 to 16 years),
      six (out of 30) TKA knees needed subsequent surgery versus only one with cell
      therapy. The Knee Score had improved and remained similar in the TKA and cell
      therapy groups (respectively 80.3 points +/- 11 versus 78.3 +/- 23); 21 patients
      preferred the knee with cell therapy and 9 preferred the knee with TKA. Knees
      with cell therapy had improvement on cartilage and bone marrow lesions observed
      at the site of bone marrow subchondral injection. CONCLUSIONS: Subchondral
      autologous bone marrow concentrate was an effective procedure for treating young
      patients with knee osteoarthritis following secondary ON of the knee related to
      corticosteroids with a lower complication rate and a quicker recovery as compared
      with TKA.

PMID- 29589087
TI  - Imbalanced bone turnover markers and low bone mineral density in patients with
      osteonecrosis of the femoral head.
AB  - PURPOSE: There have been few studies investigating the cumulative effect of
      individual factors related to bone metabolism on the systemic balance between
      bone formation and resorption in patients with osteonecrosis of the femoral head
      (ONFH). We investigated bone mineral density (BMD) of lumbar spine and bone
      turnover markers that reflect systemic bone metabolism. METHODS: Two-hundred
      twenty patients with ONFH were matched to 220 healthy subjects according to age,
      gender, and body mass index. ONFH patients were divided into steroid-induced
      (18%), alcoholic (21%), and idiopathic ONFH (61%) and subgroup analysis was
      performed to exclude the effect of steroid and malnutrition on bone metabolism.
      We compared lumbar spine bone mineral density (BMD) between groups and measured
      serum bone-specific alkaline phosphatase (BALP) and urinary
      deoxypyridinoline/creatinine (Dpd/Cr) ratio. RESULTS: Logistic regression
      analysis revealed low spine BMD was significantly associated with each subgroup
      of ONFH when compared with that of the control group (odds ratio of 2.27, 4.24,
      and 1.86 in alcoholic, steroid, and idiopathic ONFH, respectively). The mean
      value of serum BALP (27.02 U/L) was within the normal reference range while
      average urine Dpd/Cr ratio (6.24 nM/mM) increased in ONFH group when compared
      with respective reference range. CONCLUSION: Spine BMD decreased and urinary
      Dpd/Cr ratio increased in patients with non-traumatic ONFH. Further studies will
      be necessary to identify whether non-traumatic ONFH is merely a regional disease
      confined to the femoral head or may affect systemic bone metabolism.

PMID- 29589088
TI  - Total knee arthroplasties from the origin to navigation: history, rationale,
      indications.
AB  - Since the early 1970s, total knee arthroplasties have undergone many changes in
      both their design and their surgical instrumentation. It soon became apparent
      that to improve prosthesis durability, it was essential to have instruments which
      allowed them to be fitted reliably and consistently. Despite increasingly
      sophisticated surgical techniques, preoperative objectives were only met in 75%
      of cases, which led to the development, in the early 1990s, in Grenoble (France),
      of computer-assisted orthopaedic surgery for knee prosthesis implantation. In the
      early 2000s, many navigation systems emerged, some including pre-operative
      imagery ("CT-based"), others using intra-operative imagery ("fluoroscopy-based"),
      and yet others with no imagery at all ("imageless"), which soon became the
      navigation "gold standard". They use an optoelectronic tracker, markers which are
      fixed solidly to the bones and instruments, and a navigation workstation
      (computer), with a control system (e.g. pedal). Despite numerous studies
      demonstrating the benefit of computer navigation in meeting preoperative
      objectives, such systems have not yet achieved the success they warrant, for
      various reasons we will be covering in this article. If the latest navigation
      systems prove to be as effective as the older systems, they should give this type
      of technology a well-deserved boost.

PMID- 29589090
TI  - ?

PMID- 29589091
TI  - [HBM-I values for Perfluorooctanoic acid (PFOA) and Perfluorooctanesulfonic acid
      (PFOS) in blood plasma - Statement of the German Human Biomonitoring Commission
      (HBM Commission)].

PMID- 29589089
TI  - Tetraspanin-enriched microdomains regulate digitation junctions.
AB  - Tetraspanins co-emerged with multi-cellular organisms during evolution are
      typically localized at the cell-cell interface, and form tetraspanin-enriched
      microdomains (TEMs) by associating with each other and other membrane molecules.
      Tetraspanins affect various biological functions, but how tetraspanins engage in
      multi-faceted functions at the cellular level is largely unknown. When cells
      interact, the membrane microextrusions at the cell-cell interfaces form dynamic,
      digit-like structures between cells, which we term digitation junctions (DJs). We
      found that (1) tetraspanins CD9, CD81, and CD82 and (2) TEM-associated molecules
      integrin alpha3beta1, CD44, EWI2/PGRL, and PI-4P are present in DJs of
      epithelial, endothelial, and cancer cells. Tetraspanins and their associated
      molecules also regulate the formation and development of DJs. Moreover, (1) actin
      cytoskeleton, RhoA, and actomyosin activities and (2) growth factor receptor-Src
      MAP kinase signaling, but not PI-3 kinase, regulate DJs. Finally, we showed that
      DJs consist of various forms in different cells. Thus, DJs are common,
      interactive structures between cells, and likely affect cell adhesion, migration,
      and communication. TEMs probably modulate various cell functions through DJs. Our
      findings highlight that DJ morphogenesis reflects the transition between cell
      matrix adhesion and cell-cell adhesion and involves both cell-cell and cell
      matrix adhesion molecules.

PMID- 29589092
TI  - [Indoor air guide values for 2-phenoxyethanol].

PMID- 29589093
TI  - The bZIP transcriptional factor activator protein-1 regulates Metarhizium rileyi
      morphology and mediates microsclerotia formation.
AB  - Internal oxidative stress can trigger microsclerotia (MS) formation of
      Metarhizium rileyi in liquid culture. Activator protein 1 (AP1) is a
      transcription factor and an important determinant of the response to oxidative
      stress. To investigate how M. rileyi responds to internal oxidative stress and
      how MS development is regulated, the Mrap1 gene was characterized. Mrap1 was
      highly expressed during periods of invasive hyphal growth and in response to
      changing culture conditions during MS development. Compared with the wild-type
      and complemented strains, DeltaMrap1 mutants exhibited various defects in aerial
      hyphal growth, yeast-to-hypha transition, and conidia and MS formation.
      DeltaMrap1 mutants also displayed sensitivity to oxidative stress, were
      morphologically abnormal, and responded differently to oxidative stress during MS
      development. DeltaMrap1 mutants had significantly reduced conidial (74-82%) and
      MS (99%) yields. Insect bioassays revealed that DeltaMrap1 mutants displayed
      reduced virulence in topical (43-76%) and injection (45-70%) bioassays. Moreover,
      the ability of DeltaMrap1 mutants to grow out of the cuticle was reduced due to
      impaired conidiation on the host cadaver. Digital gene expression profiling
      revealed that genes involved in antioxidation, pigment biosynthesis, and ion
      transport were regulated by Mrap1 during MS development. Taken together, our
      results confirm the importance of Mrap1 in vegetative growth, conidia and MS
      formation, and virulence.

PMID- 29589094
TI  - Impact of dietary compounds on cancer-related gut microbiota and microRNA.
AB  - Cancer is one of the most common causes of death worldwide. Extensive research
      has been conducted on cancer; regardless, the link between cancer and diet
      remains undetermined. Recent studies have emphasized the importance of miRNAs in
      cancer-associated pathways from the perspective of dietary modulation. We
      highlighted the recent data on dietary modulation of gut microbiota and miRNAs
      related to cancer on the basis of recently published results. The targets of
      miRNAs are oncogenes or tumor suppressors that mediate the progression and
      initiation of carcinogenesis. Different miRNAs display complex expression
      profiles in response to dietary manipulation. Various dietary components, such as
      fatty acids, resveratrol, isothiocyanate, and curcumin, have been effectively
      used in cancer prevention and treatment. This potency is attributed to the
      capability of these components to alter miRNA expression, thereby modulating the
      vital pathways involved in metastasis, invasion, apoptosis, tumor growth, and
      cell proliferation.

PMID- 29589095
TI  - Wound healing applications of biogenic colloidal silver and gold nanoparticles:
      recent trends and future prospects.
AB  - Nanotechnology has emerged as a prominent scientific discipline in the
      technological revolution of this millennium. The scientific community has focused
      on the green synthesis of metal nanoparticles as compared to physical and
      chemical methods due to its eco-friendly nature and high efficacy. Medicinal
      plants have been proven as the paramount source of various phytochemicals that
      can be used for the biogenic synthesis of colloidal silver and gold nanoparticles
      as compared to other living organisms, e.g., microbes and fungi. According to
      various scientific reports, the biogenic nanoparticles have shown promising
      potential as wound healing agents. However, not a single broad review article was
      present that demonstrates the wound healing application of biogenic silver and
      gold nanoparticles. Foreseeing the overall literature published, we for the first
      time intended to discuss the current trends in wound healing via biogenic silver
      and gold nanoparticles. Furthermore, light has been shed on the mechanistic
      aspects of wound healing along with futuristic discussion on the faith of
      biogenic silver and gold nanoparticles as potential wound healing agents.

PMID- 29589096
TI  - The history of the formation of the Pan African paediatric surgical Association
      (PAPSA).
AB  - Political change in the 1990s in Southern Africa influenced the long awaited
      formation of a children's surgical association in Africa. Here, within is the
      historical account of the formation of the Pan African Association of Paediatric
      Surgeons (PAPSA). The basis of the argument for the formation of PAPSA was that
      paediatric surgeons from Africa have a wealth of experience and special knowledge
      of diseases affecting children in the African continent which differ
      substantially from those encountered in other regions of the world. This
      historical account is mainly from documentation by 2 of the organisations
      founding members.

PMID- 29589097
TI  - An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer's
      disease.
AB  - Mutations leading to premature termination codons in ATP-Binding Cassette
      Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's
      disease (AD). The influence of other genetic variants in ABCA7 and downstream
      functional mechanisms, however, is poorly understood. To address this knowledge
      gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of
      1529 AD patients and control individuals and identified an intronic variable
      number tandem repeat (VNTR). We observed strong association between VNTR length
      and a genome-wide associated signal for AD in the ABCA7 locus. Expanded VNTR
      alleles were highly enriched in AD patients [odds ratio = 4.5 (1.3-24.2)], and
      VNTR length inversely correlated with amyloid beta1-42 in cerebrospinal fluid and
      ABCA7 expression. In addition, we identified three novel ABCA7 alternative
      splicing events. One isoform in particular-which is formed through exon 19
      skipping-lacks the first nucleotide binding domain of ABCA7 and is abundant in
      brain tissue. We observed a tight correlation between exon 19 skipping and VNTR
      length. Our findings underline the importance of studying repetitive DNA in
      complex disorders and expand the contribution of genetic and transcript variation
      in ABCA7 to AD.

PMID- 29589098
TI  - Two-Year Clinical Outcomes of the CONSEQUENT Trial: Can Femoropopliteal Lesions
      be Treated with Sustainable Clinical Results that are Economically Sound?
AB  - PURPOSE: The previously reported 6-month angiographic and 12-month clinical
      outcomes of the CONSEQUENT trial demonstrated the safety and efficacy of a novel
      paclitaxel-resveratrol-coated balloon for the treatment of lesions in the
      femoropopliteal segment. The purpose of this report is to present the 2-year
      results including a cost-benefit analysis for Germany. MATERIALS AND METHODS:
      Patients with symptomatic peripheral artery occlusive disease in femoropopliteal
      lesions were randomized either to drug-coated balloon (DCB, n = 78) or plain old
      balloon angioplasty (POBA, n = 75). As secondary endpoints, the 2-year clinical
      results consisting of target lesion revascularization (TLR), patency and increase
      in walking distance were recorded. Based on the Kaplan-Meier analyses for TLR and
      other adverse events, a cost-benefit analysis was conducted for the German DRG
      system. RESULTS: There were no additional TLRs in both groups between 14 and 24
      months so that the corresponding rates remained significantly different between
      the treatment groups (DCB: 19.1 vs. POBA 40.6%, p = 0.007). At 2 years, the
      patency rate was significantly higher in the DCB group (72.3 vs. 48.4%, p =
      0.006). The walking distance increase was also significantly higher after DCB
      angioplasty (172 +/- 103 vs. 52 +/- 136 m, p = 0.001). We estimated 2-year cost
      savings of ? 1111.97 per patient treated with DCB instead of POBA. CONCLUSIONS:
      The use of paclitaxel-resveratrol matrix-coated peripheral balloons compared to
      POBA was associated with a significantly reduced TLR rate, superior patency and
      substantial cost savings at 2 years. ClinicalTrials.gov Identifier NCT01970579.

PMID- 29589099
TI  - Computer tomographic assessment of postoperative peripancreatic collections after
      distal pancreatectomy.
AB  - BACKGROUND: Peripancreatic collections occur frequently after distal
      pancreatectomy. However, the sequelae of peripancreatic collections vary from
      case to case, and their clinical impact is uncertain. In this study, the
      correlations between CT findings of peripancreatic collections and complications
      after distal pancreatectomy were investigated. METHODS: Ninety-six consecutive
      patients who had undergone distal pancreatectomy between 2010 and 2015 were
      retrospectively investigated. The extent and heterogeneity of peripancreatic
      collections and background clinicopathological characteristics were analyzed. The
      extent of peripancreatic collections was calculated based on three-dimensional
      computed tomography images, and the degree of heterogeneity of peripancreatic
      collections was assessed based on the standard deviation of their density on
      computed tomography. RESULTS: Of 85 patients who underwent postoperative computed
      tomography imaging, a peripancreatic collection was detected in 77 (91%).
      Patients with either a large extent or a high degree of heterogeneity of
      peripancreatic collection had a significantly higher rate of clinically relevant
      pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval
      2.12-19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87-24.19, p =
      0.0001, respectively). CONCLUSIONS: A large and heterogeneous peripancreatic
      collection was significantly associated with postoperative complications,
      especially clinically relevant postoperative pancreatic fistula. A small and
      homogenous peripancreatic collection could be safely observed.

PMID- 29589100
TI  - Genetic susceptibility to neuroblastoma: current knowledge and future directions.
AB  - Neuroblastoma, a malignancy of the developing peripheral nervous system that
      affects infants and young children, is a complex genetic disease. Over the past
      two decades, significant progress has been made toward understanding the genetic
      determinants that predispose to this often lethal childhood cancer. Approximately
      1-2% of neuroblastomas are inherited in an autosomal dominant fashion and a
      combination of co-morbidity and linkage studies has led to the identification of
      germline mutations in PHOX2B and ALK as the major genetic contributors to this
      familial neuroblastoma subset. The genetic basis of "sporadic" neuroblastoma is
      being studied through a large genome-wide association study (GWAS). These efforts
      have led to the discovery of many common susceptibility alleles, each with modest
      effect size, associated with the development and progression of sporadic
      neuroblastoma. More recently, next-generation sequencing efforts have expanded
      the list of potential neuroblastoma-predisposing mutations to include rare
      germline variants with a predicted larger effect size. The evolving
      characterization of neuroblastoma's genetic basis has led to a deeper
      understanding of the molecular events driving tumorigenesis, more precise risk
      stratification and prognostics and novel therapeutic strategies. This review
      details the contemporary understanding of neuroblastoma's genetic predisposition,
      including recent advances and discusses ongoing efforts to address gaps in our
      knowledge regarding this malignancy's complex genetic underpinnings.

PMID- 29589101
TI  - Regression of human cirrhosis: an update, 18 years after the pioneering article
      by Wanless et al.
AB  - Cirrhosis has been traditionally viewed as an irreversible, end-stage condition.
      Eighteen years ago, Wanless, Nakashima, and Sherman published a study that was
      based on the concept that hepatic architecture is under constant remodeling in
      the course of chronic liver diseases, even during their most advanced stages;
      depending on the balance between injury and repair, the histologic changes might
      be progressing or regressing. These authors described in detail the morphologic
      features of regressing cirrhosis, identified a set of histologic features of
      regression that they called the "hepatic repair complex," and provided convincing
      morphologic evidence that incomplete septal cirrhosis represents regressed
      cirrhosis. In the years that followed publication of this pioneering article, a
      number of clinical studies with performance of pre- and post-treatment liver
      biopsies provided abundant evidence that cirrhosis can regress after successful
      therapy of chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, and
      genetic hemochromatosis. Evidence for other chronic liver diseases may also be
      provided in the future, pending ongoing studies. Successful therapy allows
      resorption of fibrous septa, which can be followed by loss of nodularity and
      architectural improvement; however, many vascular lesions of cirrhotic livers are
      not thought to regress. Cases of cirrhosis that are considered more likely to
      improve than others include those of recent onset, with relatively thin fibrous
      septa and mild vascular changes. Histologic examination of liver biopsy specimens
      from patients with chronic liver diseases provides the opportunity to appreciate
      the features of the hepatic repair complex on a routine diagnostic basis;
      however, interpretation is often difficult, and can be aided by
      immunohistochemical stains. Clinicopathologic correlation is essential for a
      meaningful assessment of such cases. For many patients, cirrhosis is not an end
      stage condition anymore; therefore, use of the term "cirrhosis" has been
      challenged, almost 200 years after its invention. However, regression of
      cirrhosis does not imply regression of molecular changes involved in
      hepatocarcinogenesis; therefore, surveillance for hepatocellular carcinoma should
      be continued in these patients.

PMID- 29589104
TI  - New associate editor: PD Dr. T. Burkhardt.

PMID- 29589102
TI  - Dilemmas for the pathologist in the oncologic assessment of pancreatoduodenectomy
      specimens : An overview of different grossing approaches and the relevance of the
      histopathological characteristics in the oncologic assessment of
      pancreatoduodenectomy specimens.
AB  - A pancreatoduodenectomy specimen is complex, and there is much debate on how it
      is best approached by the pathologist. In this review, we provide an overview of
      topics relevant for current clinical practice in terms of gross dissection, and
      macro- and microscopic assessment of the pancreatoduodenectomy specimen with a
      suspicion of suspected pancreatic cancer. Tumor origin, tumor size, degree of
      differentiation, lymph node status, and resection margin status are universally
      accepted as prognostic for survival. However, different guidelines diverge on
      important issues, such as the diagnostic criteria for evaluating the completeness
      of resection. The macroscopic assessment of the site of origin in periampullary
      tumors and cystic lesions is influenced by the grossing method. Bi-sectioning of
      the head of the pancreas may offer an advantage in this respect, as this method
      allows for optimal visualization of the periampullary area. However, a head-to
      head comparison of the assessment of clinically relevant parameters, using axial
      slicing versus bi-sectioning, is not available yet and the gold standard to
      compare both techniques prospectively might be subject of debate. Further studies
      are required to validate the various dissection protocols used for
      pancreatoduodenectomy specimens and their specific value in the assessment of
      pathological parameters relevant for prognosis.

PMID- 29589105
TI  - Chromosome ends as adaptive beginnings: the potential role of dysfunctional
      telomeres in subtelomeric evolvability.
AB  - Telomeres serve as protective caps that help the cell differentiate between the
      naturally occurring ends of chromosomes and double-stranded breaks. When telomere
      capping function becomes compromised, chromosome ends are subjected to elevated
      rates of chromosome alterations. These effects can be particularly dramatic in
      the telomere-adjacent subtelomeric region. While the catastrophic impact of
      severe telomere dysfunction on genome stability has been well documented, the
      adaptive telomere failure hypothesis considers an alternative role telomere
      dysfunction may play in adaptive evolution. This hypothesis suggests that low
      levels of telomere failure, induced by certain environmental stresses, can lead
      to elevated subtelomeric recombination. Mutational loss, duplication, or
      modification of subtelomeric contingency genes could ultimately facilitate
      adaptation by generating novel mutants better able to survive environmental
      stress. In this perspective, we discuss recent work that examined mild telomere
      dysfunction and its role in altering the adaptive potential of subtelomeric
      genes.

PMID- 29589106
TI  - Macular buckle technique in myopic traction maculopathy: a 16-year review of the
      literature and a comparison with vitreous surgery.
AB  - PURPOSE: The aim of this study is to review anatomical and functional outcomes
      following macular buckling (MB) in high myopia and to compare such results with
      those obtained by pars plana vitrectomy (PPV). METHODS: PubMed articles on MB in
      high myopia (2000-2016) were reviewed. Main outcomes included retinal
      reattachment and macular hole (MH) closure rates, resolution of myopic
      foveoschisis (MFS), and postoperative visual acuity. RESULTS: Thirty-one articles
      included 16 in patients with retinal detachment due to MH (MHRD group), 11 in MFS
      with or without foveal detachment (MFS group), and 4 in MH patients with MFS (MH
      MFS group). Surgical techniques mainly differed in the type of buckle, rectus
      muscles involvement, and concurrent PPV. In eyes with persistent MH, prognosis in
      the MHRD and MH-MFS groups differed between eyes receiving MB compared to PPV:
      functional outcome was markedly poorer and there was a higher risk of retinal
      redetachment associated with PPV. In the MSF group, secondary MHs were more
      likely to develop in eyes treated with PPV and internal limiting membrane peeling
      than those undergoing MB alone or combined with PPV. Retinal pigment epithelium
      changes, malpositioning, perforation, and choroidal detachment were the main
      complications. CONCLUSIONS: Although different approaches are used, complete
      resolution of foveoschisis, retinal reattachment, and MH closure seem to be
      achieved more frequently with MB than PPV.

PMID- 29589107
TI  - Rhu-Epo down-regulates pro-tumorigenic activity of cancer-associated fibroblasts
      in multiple myeloma.
AB  - We have previously demonstrated that recombinant human erythropoietin (rHuEpo) is
      involved in the regulation of the angiogenic response in multiple myeloma (MM)
      through a direct effect on macrophages and endothelial cells isolated from the
      bone marrow of patients with MM. The aim of the present study was designed to
      determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from
      monoclonal gammopathy of undetermined significance (MGUS) and MM patients by
      means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of
      mRNA levels of fibroblast activation markers, namely alpha smooth actin
      (alphaSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of
      pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and
      IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2
      (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs. Moreover, rHuEpo inhibits
      the proliferative activity of MM CAFs and increased the apoptosis of MGUS and MM
      CAFs. Overall, these data suggest that rHu-Epo down-regulates CAFs pro
      tumorigenic activity. Moreover, these results are not suggestive for a pro
      angiogenic activity of rHuEpo on CAFs. In fact, rHuEpo pre-treatment induces a
      low angiogenic response in vivo in the chorioallantoic membrane (CAM) assay of
      MGUS and MM CAFs conditioned medium, not comparable to that of a well-known
      angiogenic cytokine, VEGF-A, tested in the same assay.

PMID- 29589109
TI  - Prevalence and associated factors of preoperative functional disability in
      elective surgical patients over 55 years old: a prospective cohort study.
AB  - PURPOSE: In preoperative settings, patients may have functional disabilities due
      to the disease for which surgery is being performed or comorbidities, but the
      associated and predictive factors remain unknown. This study examined the
      prevalence of preoperative functional disability and clarified the associated
      factors. METHODS: Individuals aged >= 55 years who were scheduled to undergo
      surgery in a tertiary-care hospital in Japan between April 2016 and September
      2016 were eligible for enrolment in the study. Patients with the diseases
      requiring psychiatric treatment and patients unable to complete the questionnaire
      without help were excluded. After obtaining informed consent, each patient was
      asked to complete the 12-item World Health Organization Disability Assessment
      Schedule-2.0, which is a standardized evaluation tool for assessing comprehensive
      living function. Data from these questionnaires and the patients' characteristics
      were evaluated. Multiple logistic regression analysis was conducted to determine
      independent factors associated with preoperative functional disability. RESULTS:
      Of 1201 recruited patients, 912 (75.9%) were included in our analysis. The
      prevalence of preoperative functional disability was 29.2%. Regression analysis
      identified six independent associated factors for preoperative functional
      disability: body mass index >= 30 kg m-2, mixed lung disease, serum albumin
      values, malnutrition, risk of malnutrition, and preoperative use of
      corticosteroids. CONCLUSIONS: In total, 29.2% of preoperative patients had
      functional disability. Obesity, nutritional deficiency, respiratory
      complications, and low serum albumin values were determined as potentially
      modifiable factors.

PMID- 29589108
TI  - Chronic diarrhoea following surgery for colon cancer-frequency, causes and
      treatment options.
AB  - PURPOSE: The growing population of survivors after colon cancer warrants
      increased attention to the long-term outcome of surgical treatment. The change in
      bowel anatomy after resection disrupts normal gastrointestinal function and may
      cause symptoms. Thus, many patients surviving colon cancer have to cope with
      bowel dysfunction for the rest of their lives. We here aim to provide an overview
      of the literature on this topic. METHODS: We review long-term functional outcomes
      of surgical treatment for colon cancer, the underlying pathology, and treatment
      options. RESULTS: Common symptoms include constipation, urge for defecation and
      diarrhoea. Causes of diarrhoea after colon cancer surgery are sparsely studied,
      but they probably include bile acid malabsorption, small intestinal bacterial
      overgrowth and disruption of the ileal brake. Specific diagnosis should be made
      to allow individual treatment based on the underlying pathology. Studies on
      treatment of functional problems after surgery for colon cancer are extremely
      few, but some lessons can be drawn from the treatment of other patient groups
      having undergone colon surgery. CONCLUSION: Diarrhoea is likely a common long
      term complication after colon cancer surgery. Attention to this complication and
      a specific diagnosis will aid the targeted treatment of patients suffering from
      this complication.

PMID- 29589110
TI  - Protein-bounded uremic toxin p-cresylsulfate induces vascular permeability
      alternations.
AB  - The goal of the present studies is to investigate that the impact of p
      cresylsulfate (PCS) on the endothelial barrier integrity via in situ exposure and
      systemic exposure. Vascular permeability changes induced by local injection of
      PCS were evaluated by the techniques of both Evans blue (EB) and India ink
      tracer. Rats were intravenously injected with EB or India ink followed by
      intradermal injections of various doses of PCS (0, 0.4, 2, 10 and 50 umol/site)
      on rat back skins. At different time points, skin EB was extracted and
      quantified. The administration of India ink was used to demonstrate leaky
      microvessels. Skin PCS levels were also determined by liquid chromatography-mass
      spectrometry. We also investigated whether the increased endothelial leakage
      occurred in the aortic endothelium in rats treated with 5/6 nephrectomy and
      intraperitoneal injection of PCS 50 mg/kg/day for 4 weeks. The aortic endothelial
      integrity was evaluated by increased immunoglobulin G (IgG) leakage. High doses
      of PCS, but not lower doses, significantly induced vascular leakage as compared
      to saline injection and EB leakage exhibited in time-dependent manner. A time
      correlated increase in leaky microvessels was detected in the tissues examined.
      The injected PCS declined with time and displayed an inverse relationship with
      vascular leakage. Chronic kidney disease (CKD) rats administered with PCS,
      compared to control rats, had significantly higher serum levels of PCS and
      apparent IgG deposition in the aortic intima. Increased endothelial leakage
      induced by PCS in skin microvessels and the aorta of CKD rats suggests that the
      PCS-induced endothelial barrier dysfunction.

PMID- 29589111
TI  - Effects of resistance training on MRI-derived epicardial fat volume and arterial
      stiffness in women with obesity: a randomized pilot study.
AB  - AIM: To date, few studies have analyzed the effects of exercise on cardiac
      adipose tissue. Overall, exercise programs did not meet the recommendations for
      significant weight loss, the utilization of resistance training was minimal, and
      the conclusions derived from these studies have diminished exercise as a strategy
      for cardiac fat loss. PURPOSE: The objective of this pilot study was to analyze
      the effects of 3-week high-intensity, moderate-volume muscular endurance
      resistance training (RT) on cardiac fat and arterial stiffness. METHODS: A total
      of 11 young females with obesity, BMI = 34.13 (+/- 3.16) kg/m2 (n = 5 control, n
      = 6 intervention) completed the study. Absolute strength was assessed using one
      repetition maximum test (1RM) for bench press (BP) and leg press (LP), and
      relative strength was calculated using body weight (BW) as BP-to-BW and LP-to-BW
      ratio. Magnetic resonance was used to quantify epicardial and paracardial adipose
      tissue (EAT and PAT) volume, and applanation tonometry was used to assess
      arterial stiffness by estimating pulse wave velocity (PWV). RESULTS: EAT and PAT
      volumes (ml) showed significant interaction effects (p = 0.037 and p = 0.031),
      and very large changes (d > 1) of EAT (p = 0.006) and PAT (p = 0.036) in the
      intervention group. In addition, strength was significantly improved, including
      BP (p = 0.003), LP (p = 0.001), BP-to-BW ratio (p = 0.001), and LP-to-BW ratio (p
      = 0.002), while no changes were found in PWV. CONCLUSIONS: High-intensity,
      moderate-volume RT, designed to enhance muscular endurance following the
      recommendations reduces EAT and PAT volumes, improves physical fitness in females
      with obesity, and has no negative effects on arterial stiffness.

PMID- 29589112
TI  - Complications following ultrasound-guided core needle biopsy of thyroid nodules:
      a systematic review and meta-analysis.
AB  - OBJECTIVES: To identify the complication rate associated with US-guided core
      needle biopsy (CNB) of thyroid lesions using a systematic review and meta
      analysis. METHODS: Ovid-MEDLINE and EMBASE databases were searched for studies on
      US-guided CNB of thyroid lesions from 1 January 1994-13 December 2016. A review
      of 393 potential papers identified 39 eligible papers including 14,818 patients.
      The pooled proportions of complications were assessed using random-effects
      modelling. Subgroup analysis was performed. Among-study heterogeneity was
      explored using chi2 statistic for pooled estimates and inconsistency index I2.
      Quality of the studies was evaluated using the Risk of Bias Assessment Tool for
      Nonrandomized Studies. RESULTS: The pooled proportion of overall complications
      after CNB of thyroid lesions was 1.11% (95% CI: 0.64-1.51, I2: 87.2%). The pooled
      proportion of major complications (0.06% [95% CI: 0.02-0.10], I2: 0.0%) was much
      lower than that of minor complications (1.08%[95% CI: 0.63-1.53], I2: 93.17%).
      Subgroup analysis revealed no significant differences between studies on Asian
      versus non-Asian groups (p=0.7769), radiologist versus non-radiologist groups
      (p=0.8607), nodule size <20 mm versus nodule size >=20 mm (p=0.1591) groups, CNB
      versus CNB-plus-FNA groups (p=0.9281) and studies performed before and after 2012
      (p=0.6251). The overall quality of the included studies was moderate with all of
      the studies satisfying five or more of the eight total domains. CONCLUSION:
      Various complications can occur after US-guided CNB of thyroid lesions. However,
      the procedure is safe, with a low complication rate. KEY POINTS: * Various
      complications occurred after CNB of thyroid lesions, but the pooled complication
      rate was low (1.11%, I 2 = 87.2%). * The pooled proportion of major complications
      (0.06%) was much lower than that of minor complications (1.08%). * There was no
      significant differences between studies on Asian vs. non-Asian groups,
      radiologist vs. non-radiologist groups, nodule size <20 mm vs. nodule size >=20
      mm groups, CNB vs. CNB-plus-FNA groups, or studies performed before 2012 vs.
      after 2012.

PMID- 29589113
TI  - Corticosterone level and central dopaminergic activity involved in agile and
      exploratory behaviours in formosan wood mice (Apodemus semotus).
AB  - The native Formosan wood mouse (Apodemus semotus) is the dominant rodent in
      Taiwan. In their natural environment, Formosan wood mice exhibit high locomotor
      activity, including searching and exploratory behaviours, which is observed
      similarly in the laboratory environment. How the behavioural responses of
      Formosan wood mice exhibit in elevated plus maze and marble burying tests remains
      unclear. How corticosterone levels and central dopaminergic activities are
      related to the behaviours in these tests is also unclear. This study compared the
      behaviours of Formosan wood mice with that of C57BL/6J mice using the elevated
      plus maze and marble burying tests, and measured the corticosterone levels and
      central dopaminergic activities. Formosan wood mice showed greater locomotor and
      exploratory activity than the C57BL/6J mice. Similarly, the marble burying and
      rearing numbers were higher for Formosan wood mice. High locomotor and
      exploratory behaviours were strongly correlated with corticosterone levels after
      acute mild restraint stress in Formosan wood mice. The anxiolytic, diazepam,
      reduced the high exploratory activity, corticosterone levels and central
      dopaminergic activities. The high locomotor and exploratory behaviours of
      Formosan wood mice are related to the corticosterone levels and central
      dopaminergic activities. These data may explain Formosan wood mice dominance in
      the intermediate altitude of Taiwan.

PMID- 29589114
TI  - Can neck pain be an initial symptom of rheumatoid arthritis? A case report and
      literature review.
AB  - Although rheumatoid arthritis (RA) is most commonly associated with peripheral
      joints, cervical spine involvement can be seen in almost 80% of patients in the
      presence of long-term disease, joint erosion, and risk factors such as male sex
      and rheumatoid factor positivity. It is very rare to have cervical involvement in
      the initial period of RA. If a patient has isolated cervical spine involvement
      without peripheral arthritis, it is highly likely that inappropriate
      investigations and delayed treatment may occur. Any damage that occurs in
      cervical spine may cause symptoms varying from slight instability to atlantoaxial
      subluxation, spinal cord and brain stem compression and even death. Therefore,
      physician should be aware that there may be isolated cervical involvement, albeit
      rare, in patients with RA. In this report, we presented a case of RA presenting
      with cervical spine involvement without peripheral arthritis to underline the
      importance of this kind of involvement in clinical practice. We also briefly
      reviewed other cases similar to ours in light of literature.

PMID- 29589115
TI  - Alternative Laparoscopic Intracorporeal Pringle Maneuver by Huang's Loop.
AB  - AIM: This paper aims to describe an intracorporeal tourniquet method for
      laparoscopic Pringle maneuver (PM). METHODS: One shortened Foley tube with side
      hole on the tip was put into the abdomen. Then, the tail was pulled out through
      the side-hole to make a loop to encircle porta hepatis for inflow control.
      RESULT: It is easy to keep the tension by a metallic clip, and when released, the
      clip can be removed and the loop loosened. CONCLUSION: Therefore, PM could be
      performed inside the abdomen without special instrument nor extra trocar port.
      The intracorporeal Pringle maneuver with Huang's loop could be routinely used
      during laparoscopic liver resection even for a laparoscopic beginner because it
      is so easily learnt, safe, and effective.

PMID- 29589116
TI  - Early Closure of Defunctioning Loop Ileostomy: Is It Beneficial for the Patient?
      A Meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis to answer the question, whether early
      closure (EC) of defunctioning loop ileostomy may be beneficial for patient as
      compared with late closure (LC) without exceeding the risk of surgical-related
      morbidity. DESIGN: Medline and the Cochrane Trials Register were searched for
      trials published up to November 2016 comparing EC (defined as <=14 days from the
      index operation in which the ileostomy was performed) versus LC for stoma closure
      after rectal surgery. Meta-analysis was performed using Review Manager 5.0.
      Inclusion criteria MAIN OUTCOME MEASURES: Overall morbidity rate, anastomotic
      leakage rate, and wound infection rate within 90 days after elective surgery.
      RESULTS: Six studies were included and analyzed, yielding 570 patients (252 in EC
      group and 318 in LC). Meta-analysis showed no significant difference in the
      overall morbidity rate between the EC and LC groups (OR 0.63; 95% CI, 0.22-1.78;
      P = 0.38). Despite a significant higher wound infection rate of stoma site (OR
      3.83; 95% CI 2.14-6.86; P < 0.00001), meta-analysis showed no significant
      difference in the anastomotic leakage rate between the EC and LC groups (OR 0.63;
      95% CI 0.22-1.78; P = 0.38). Moreover, both stoma-related complications (OR 0.46;
      95% CI 0.24-0.86; P = 0.02) and small bowel obstruction rates (OR 0.11; 95% CI
      0.06-0.20; P < 0.00001) were significantly lower in the EC group than in the LC
      group, respectively. LIMITATIONS: Heterogeneity of the studies CONCLUSION: This
      meta-analysis suggests that EC of a defunctioning loop ileostomy is effective and
      safe in careful selected patients without increasing overall postoperative
      complications. This promising strategy should be proposed in patients in order to
      reduce stoma-related complications.

PMID- 29589117
TI  - The degenerin region of the human bile acid-sensitive ion channel (BASIC) is
      involved in channel inhibition by calcium and activation by bile acids.
AB  - The bile acid-sensitive ion channel (BASIC) is a member of the ENaC/degenerin
      family of ion channels. It is activated by bile acids and inhibited by
      extracellular Ca2+. The aim of this study was to explore the molecular mechanisms
      mediating these effects. The modulation of BASIC function by extracellular Ca2+
      and tauro-deoxycholic acid (t-DCA) was studied in Xenopus laevis oocytes
      heterologously expressing human BASIC using the two-electrode voltage-clamp and
      outside-out patch-clamp techniques. Substitution of aspartate D444 to alanine or
      cysteine in the degenerin region of BASIC, a region known to be critically
      involved in channel gating, resulted in a substantial reduction of BASIC Ca2+
      sensitivity. Moreover, mutating D444 or the neighboring alanine (A443) to
      cysteine significantly reduced the t-DCA-mediated BASIC stimulation. A combined
      molecular docking/simulation approach demonstrated that t-DCA may temporarily
      form hydrogen bonds with several amino acid residues including D444 in the outer
      vestibule of the BASIC pore or in the inter-subunit space. By these interactions,
      t-DCA may stabilize the open state of the channel. Indeed, single-channel
      recordings provided evidence that t-DCA activates BASIC by stabilizing the open
      state of the channel, whereas extracellular Ca2+ inhibits BASIC by stabilizing
      its closed state. In conclusion, our results highlight the potential role of the
      degenerin region as a critical regulatory site involved in the functional
      interaction of Ca2+ and t-DCA with BASIC.

PMID- 29589118
TI  - Tick-borne pathogens in tick species infesting humans in Sibiu County, central
      Romania.
AB  - Romania has a highly diverse tick fauna. Consequently, a high diversity of tick
      transmitted pathogens might be a potential threat to humans. However, only a
      limited number of tick species regularly infest humans, and pathogens present in
      such species are therefore of particular interest from a medical perspective. In
      this study, 297 ticks were collected from humans during 2013 and 2014. Ixodes
      ricinus was the predominant tick species, accounting for 272 specimens or 91.6%
      of the ticks in the study. Nevertheless, other tick species were also found to
      infest humans: Dermacentor marginatus constituted 7% of the ticks found on humans
      (21/297), Haemaphysalis punctata 1% (3/297), and Haemaphysalis concinna 0.3%
      (1/297). Ticks were tested by PCR for a wide range of tick-borne pathogens. In
      total, 11.8% of the ticks carried human pathogenic bacteria, while no viral or
      protozoan pathogens were detected. The most frequently detected pathogen was
      Rickettsia spp., occurring in 5.4% of the ticks (16/297) and comprising three
      species: Rickettsia (R.) raoultii, R. monacensis, and R. helvetica. Borrelia s.l.
      occurred in 3% (9/297) of the ticks. "Candidatus Neoehrlichia mikurensis"
      occurred in 1.7% (5/297) and Anaplasma phagocytophilum in 1.3% (4/297). Anaplasma
      bovis was detected in an H. punctata and Borrelia miyamotoi in an I. ricinus.
      These results point to the need for further studies on the medical importance of
      tick-borne pathogens in Romania.

PMID- 29589119
TI  - Dairy products intake and the risk of incident cataracts surgery in an elderly
      Mediterranean population: results from the PREDIMED study.
AB  - PROPOSAL: The aim of this study was to examine the association between the
      consumption of total and specific types of dairy products and the risk of
      incident cataracts in an elderly Mediterranean population at high cardiovascular
      risk. METHODS: We prospectively analyzed 5860 subjects from the PREvencion con
      DIeta MEDiterranea (PREDIMED) Study. The time to cataract surgery was calculated
      as the time between recruitment and the date of the surgery, last visit of the
      follow-up, date of death, or until the end of the study. Dairy products intake
      was assessed using validated food frequency questionnaires. We used Cox
      proportional hazard regression to assess the risk of cataract surgery according
      to average dietary energy-adjusted total dairy products, milk, yogurt and cheese
      consumption. RESULTS: We documented a total of 768 new cataract events after a
      median of 5.6 years of follow-up. Subjects in the second [hazard ratio (HR) 0.62;
      95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed
      yogurt intake had a significantly lower risk of cataracts after adjusting for
      potential confounders. No significant associations were observed for total dairy
      products, whole and skimmed milk, whole yogurt and cheese consumption.
      CONCLUSION: The intake of skimmed yogurt was associated with a reduced risk of
      cataracts in an elderly Mediterranean population with high cardiovascular risk.
      No significant associations were observed for other type of dairy product.
      CLINICAL TRIAL REGISTRATION: International Standard Randomized Controlled Trial
      Number (ISRCTN): 35739639. Registration date: 5 October 2005.

PMID- 29589120
TI  - Patient Access to Academic Cancer Centers.

PMID- 29589121
TI  - Sigmund Freud-early network theories of the brain.
AB  - Since the early days of modern neuroscience, psychological models of brain
      function have been a key component in the development of new knowledge. These
      models aim to provide a framework that allows the integration of discoveries
      derived from the fundamental disciplines of neuroscience, including anatomy and
      physiology, as well as clinical neurology and psychiatry. During the initial
      stages of his career, Sigmund Freud (1856-1939), became actively involved in
      these nascent fields with a burgeoning interest in functional neuroanatomy. In
      contrast to his contemporaries, Freud was convinced that cognition could not be
      localised to separate modules and that the brain processes cognition not in a
      merely serial manner but in a parallel and dynamic fashion-anticipating
      fundamental aspects of current network theories of brain function. This article
      aims to shed light on Freud's seminal, yet oft-overlooked, early work on
      functional neuroanatomy and his reasons for finally abandoning the conventional
      neuroscientific "brain-based" reference frame in order to conceptualise the mind
      from a purely psychological perspective.

PMID- 29589122
TI  - Simultaneous determination of estrone and selected pesticides in water medium by
      GC-MS after multivariate optimization of microextraction strategy.
AB  - A sensitive and accurate analytical method based on dispersive liquid-liquid
      microextraction was developed for the simultaneous determination of selected
      pesticides, hormones, and endocrine disruptors by GC-MS. The optimum conditions
      of the extraction procedure were determined using an experimental design of
      factors significantly affecting the extraction output. Analysis of variance
      (ANOVA) was used to evaluate the main effects of experimental factors and their
      interactions. The limit of detection values determined for the analytes under
      optimum experimental conditions were found to be between 0.30-2.0 ng/mL. The
      linear calibration plot of analytes span across a wide concentration range and
      low %RSD values from replicate measurements indicated good precision of the
      developed method. Spiked recovery tests were also performed on municipal
      wastewater, well water, lake water, sea water, and tap water matrices to
      determine the method's accuracy and applicability to water samples. The recovery
      results obtained were satisfactory for all water samples.

PMID- 29589123
TI  - Phylogenetic and functional implications of the ear region anatomy of
      Glossotherium robustum (Xenarthra, Mylodontidae) from the Late Pleistocene of
      Argentina.
AB  - Several detailed studies of the external morphology of the ear region in extinct
      sloths have been published in the past few decades, and this anatomical region
      has proved extremely helpful in elucidating the phylogenetic relationships among
      the members of this mammalian clade. Few studies of the inner ear anatomy in
      these peculiar animals were conducted historically, but these are increasing in
      number in recent years, in both the extinct and extant representatives, due to
      wider access to CT-scanning facilities, which allow non-destructive access to
      internal morphologies. In the present study, we analyze the extinct ground sloth
      Glossotherium robustum and provide a description of the external features of the
      ear region and the endocranial side of the petrosal bone, coupled with the first
      data on the anatomy of the bony labyrinth. Some features observable in the ear
      region of G. robustum (e.g., the shape and size of the entotympanic bone and the
      morphology of the posteromedial surface of the petrosal) are highly variable,
      both intraspecifically and intraindividually. The form of the bony labyrinth of
      G. robustum is also described, providing the first data from this anatomical
      region for the family Mylodontidae. The anatomy of the bony labyrinth of the
      genus Glossotherium is here compared at the level of the superorder Xenarthra,
      including all available extant and extinct representatives, using geometric
      morphometric methods. In light of the new data, we discuss the evolution of inner
      ear anatomy in the xenarthran clade, and most particularly in sloths, considering
      the influence of phylogeny, allometry, and physiology on the shape of this highly
      informative region of the skull. These analyses show that the inner ear of
      Glossotherium more closely resembles that of the extant anteaters, and to a
      lesser extent those of the giant ground sloth Megatherium and euphractine
      armadillos, than those of the extant sloths Bradypus and Choloepus, further
      demonstrating the striking morphological convergence between the two extant sloth
      genera.

PMID- 29589125
TI  - Cadmium in the shore crab Carcinus maenas along the Norwegian coast: geographical
      and seasonal variation and correlation to physiological parameters.
AB  - Previously, high concentrations of cadmium have been found in the hepatopancreas
      of the edible or brown crab (Cancer pagurus) sampled from positions north of
      about 67 degrees  N, compared to regions further south along the Norwegian coast,
      with no clear understanding why. In order to study a similar organism in the same
      ecosystem, the present study analyzed 210 shore crabs (Carcinus maenas) from four
      different locations along the Norwegian coast, two in the North and two in the
      South. The physiological variables size, sex, molting stage, hepatosomatic index,
      carapace color, and gonad maturation were registered, in attempt to explain the
      high inter-individual variation in cadmium levels in hepatopancreas. In contrast
      to the brown crabs, the shore crabs showed no clear geographical differences in
      cadmium concentrations. This indicates physiological differences between the two
      crab species. No clear and consistent correlations were found between cadmium
      levels and physiological parameters, except for sex, where cadmium concentration
      in hepatopancreas was twice as high in males compared to females. The cadmium
      levels also varied with season, with approximately 40 and 60% lower cadmium
      concentration in April than August for male and female shore crabs, respectively.
      None of the analyzed cadmium concentrations in muscle meat from claws exceeded
      EUs food safety limit, and low cadmium levels in soup prepared from shore crabs
      clearly indicated that this dish is not problematic regarding food safety.

PMID- 29589124
TI  - Biotechnological approaches for artemisinin production in Artemisia.
AB  - Artemisinin and its analogues are naturally occurring most effective antimalarial
      secondary metabolites. These compounds also possess activity against various
      types of cancer cells, schistosomiasis, and some viral diseases. Artemisinin and
      its derivatives (A&D) are found in very low amounts in the only natural source
      i.e. Artemisia plant. To meet the global needs, plant sources have been exploited
      for the enhanced production of these natural products because their chemical
      synthesis is not profitable. The generally adopted approaches include non
      transgenic (tissue and cell cultures) and transgenic together with the cell,
      tissue, and whole transgenic plant cultures. The genes targeted for the
      overproduction of A&D include the biosynthetic pathway genes, trichome
      development genes and rol genes, etc. Artemisinin is naturally produced in
      trichomes of leaves. At the same time, transgenic hairy roots are considered a
      good source to harvest artemisinin. However, the absence of trichomes in hairy
      roots suggests that artemisinin biosynthesis is not limited to trichomes.
      Moreover, the expression of the gene involved in trichome development and
      sesquiterpenoid biosynthesis (TFAR1) in transgenic and non-transgenic roots
      provokes researchers to look for new insight of artemisinin biosynthesis. Here we
      discuss and review precisely the various biotechnological approaches for the
      enhanced biosynthesis of A&D.

PMID- 29589126
TI  - Competitive sorption of Ni and Zn at the aluminum oxide/water interface: an XAFS
      study.
AB  - Trace metals (e.g. Ni, Zn) leached from industrial and agricultural processes are
      often simultaneously present in contaminated soils and sediments. Their mobility,
      bioavailability, and ecotoxicity are affected by sorption and cosorption at
      mineral/solution interfaces. Cosorption of trace metals has been investigated at
      the macroscopic level, but there is not a clear understanding of the molecular
      scale cosorption processes due to lack of spectroscopic information. In this
      study, Ni and Zn cosorption to aluminum oxides (gamma-Al2O3) in binary-sorbate
      systems were compared to their sorption in single-sorbate systems as a function
      of pH using both macroscopic batch experiments and synchrotron-based X-ray
      absorption fine structure spectroscopy. At pH 6.0, Ni and Zn were sorbed as inner
      sphere surface complexes and competed for the limited number of reactive sites on
      gamma-Al2O3. In binary-sorbate systems, Ni had no effect on Zn sorption, owning
      to its lower affinity for the metal oxide surface. In contrast, Zn had a higher
      affinity for the metal oxide surface and reduced Ni sorption. At pH 7.5, Ni and
      Zn were sorbed as mixed-metal surface precipitates, including Ni-Al layered
      double hydroxides (LDHs), Zn-Al LDHs, and likely Ni-Zn-Al layered triple/ternary
      hydroxides. Additionally, at pH 7.5, Ni and Zn do not exhibit competitive
      sorption effects in the binary system. Taken together, these results indicated
      that pH critically influenced the reaction products, and provides a crucial
      scientific basis to understand the potential mobility, bioavailability, and
      ecotoxicity of Ni and Zn in natural and contaminated geochemical environments.

PMID- 29589127
TI  - Launching Anxious Young Adults: A Specialized Cognitive-Behavioral Intervention
      for Transitional Aged Youth.
AB  - PURPOSE OF REVIEW: There has been growing clinical and research attention to the
      unique developmental stage of emerging adulthood. This stage is a time of
      significant change and growth for all individuals, as it includes identity
      exploration, emotional, behavioral, and financial independence from caregivers,
      and completion of educational or vocational requirements. RECENT FINDINGS:
      Anxiety disorders are the most common mental health diagnoses among emerging
      adults, and individuals suffering from these disorders often experience
      compounding functional impairments across health, financial, and social domains.
      While evidence-based treatments exist for both child/adolescent anxiety disorders
      and adult anxiety disorders, no specialized assessment or treatment methods have
      been established for the unique period of emerging adulthood. Our review examines
      literature pertinent to anxiety disorders in emerging adulthood and describes a
      novel, specialized intervention to address the unique challenges faced by anxious
      emerging adults. The Launching Emerging Adults Program (LEAP) is a
      developmentally informed cognitive-behavioral treatment model that aims to
      simultaneously reduce anxiety symptoms and promote independence. We conclude with
      a discussion of lessons learned and future directions.

PMID- 29589128
TI  - Photoconductivity, pH Sensitivity, Noise, and Channel Length Effects in Si
      Nanowire FET Sensors.
AB  - Silicon nanowire (NW) field-effect transistor (FET) sensors of various lengths
      were fabricated. Transport properties of Si NW FET sensors were investigated
      involving noise spectroscopy and current-voltage (I-V) characterization. The
      static I-V dependencies demonstrate the high quality of fabricated silicon FETs
      without leakage current. Transport and noise properties of NW FET structures were
      investigated under different light illumination conditions, as well as in sensor
      configuration in an aqueous solution with different pH values. Furthermore, we
      studied channel length effects on the photoconductivity, noise, and pH
      sensitivity. The magnitude of the channel current is approximately inversely
      proportional to the length of the current channel, and the pH sensitivity
      increases with the increase of channel length approaching the Nernst limit value
      of 59.5 mV/pH. We demonstrate that dominant 1/f-noise can be screened by the
      generation-recombination plateau at certain pH of the solution or external
      optical excitation. The characteristic frequency of the generation-recombination
      noise component decreases with increasing of illumination power. Moreover, it is
      shown that the measured value of the slope of 1/f-noise spectral density
      dependence on the current channel length is 2.7 which is close to the
      theoretically predicted value of 3.

PMID- 29589129
TI  - Shared Decision-Making: a Systematic Review Focusing on Mood Disorders.
AB  - PURPOSE OF REVIEW: This study aims to provide a review of the randomized
      controlled studies evaluating the effects of shared decision-making (SDM)
      intervention in comparison to care as usual in patients with mood disorders.
      RECENT FINDINGS: Of the 14 randomized controlled studies identified, only three 6
      month studies evaluated the interest of SDM interventions using decision aids in
      depressed patients. All of them showed that the intervention effectively improved
      patient satisfaction and engagement in the decision-making process. Only one
      study in patients with bipolar disorder (BD) showed improvement of depressive
      symptoms, functioning, and quality of life. Other included studies were
      collaborative care interventions using a SDM approach in patients with depression
      in specific populations depending on age, gender, income, and physical
      comorbidities. All of them showed significant improvement in depression outcomes
      or medication adherence. SDM interventions using decision aids and collaborative
      care showed evidence of improvements in the management of depression. Stronger
      evidence of SDM interest in BD is needed.

PMID- 29589130
TI  - The tension of framed membranes from computer simulations.
AB  - We have analyzed the behavior of a randomly triangulated, self-avoiding surface
      model of a flexible, fluid membrane subject to a circular boundary by Wang-Landau
      Monte Carlo computer simulation techniques. The dependence of the canonical free
      energy and frame tension on the frame area is obtained for flexible membranes. It
      is shown that for low bending rigidities the framed membrane is only stable above
      a threshold tension, suggesting a discontinuous transition from the collapsed
      (branched polymer) state to a finite tension extended state. In a tension range
      above this threshold tension the membranes display power-law characteristics for
      the equation of state, while higher tension levels includes both an extended
      linear (elastic) as well as a highly non-linear stretching regime. For semi
      flexible membranes a transition from extended to buckled conformations takes
      place at negative frame tensions. Our analysis indicates that at zero frame
      tension the crumpling transition of fluid membranes show characteristics of both
      critical behavior and a discontinuous transition at low bending rigidities.

PMID- 29589131
TI  - Recent Progress in Pharmacogenomics of Antipsychotic Drug Response.
AB  - PURPOSE OF REVIEW: Pharmacogenomics (PGx) of antipsychotic drug response is an
      active area of research in the past few years. We reviewed recent PGx studies
      with an emphasis of development of new methodologies and new research directions.
      RECENT FINDINGS: Traditional candidate gene approach continues to generate
      evidence to support the associations of antipsychotic response with genes coding
      for drug targets such as DRD2. Genome-wide association studies have found a few
      novel genes that may be associated with drug efficacy and adverse events. Recent
      application of polygenic risk score makes it possible to combine many genetic
      variants to predict clinical response. Finally, epigenetic research including DNA
      methylation is emerging and promises new findings that potentially can be applied
      in clinical practice. New methodologies may advance PGx closer to clinical
      application. Multiple genes and epigenomic markers can be used in prediction of
      clinical phenotypes.

PMID- 29589133
TI  - Knowledge of smoking as a risk factor for disease among urology clinic patients
      in Australia.
AB  - INTRODUCTION: Smoking remains a common habit among the general population.
      Despite the well-established risks of smoking, relatively few studies have been
      undertaken to assess the understanding of these risks among the general
      population. We intended to assess the understanding of smoking as a risk factor
      for various conditions in a urology outpatient cohort to assess the level of
      knowledge as well as particular strengths and weaknesses they possess. METHODS: A
      four-page questionnaire was distributed among urology outpatients over a 5 month
      period. The questionnaire captured information regarding the knowledge of smoking
      as a risk factor for various urological and non-urological conditions. Results
      were collated and stratified according to patient's cancer history as well as
      smoking status. RESULTS: A total of 112 participants were included in our
      analytical sample. Our study demonstrated a deficiency in knowledge regarding
      smoking and urological conditions. When ranked by level of knowledge, four of the
      bottom five conditions were urological in nature. Furthermore, we found that
      patients with a personal cancer history demonstrated generally poorer knowledge
      of smoking as a risk factor compared to patients without a cancer history.
      Conversely, smokers themselves demonstrated a greater understanding of risks
      compared to non-smokers. CONCLUSIONS: Our study suggests there is much work to be
      done in the education of patients on the risks of smoking from a urological point
      of view. We believe more initiative needs to be taken by the specialists treating
      such patients to achieve an improved level of knowledge.

PMID- 29589132
TI  - Smoking quantity determines disease activity and function in Chinese patients
      with ankylosing spondylitis.
AB  - The objective of this study was to systemically and comprehensively evaluate the
      associations between smoking and disease outcomes in patients with ankylosing
      spondylitis (AS). Information on smoking, clinical features, and sociodemographic
      characteristics was collected by a questionnaire administered directly to the
      patient. Group differences were analyzed by t test or chi-square test. Logistic
      regression analysis was conducted with the Bath AS Disease Activity Index
      (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte
      sedimentation rate as the dependent variables and different stratification of
      smoking duration, smoking intensity, and cumulative smoking as independent
      variables. In order to compare our results with previous studies, meta-analysis
      was performed to calculate standardized mean difference (SMD) for relationship
      between outcomes and smoking status. A total of 1178 AS patients were analyzed.
      Compared with non-smokers, the risk of having active disease (BASDAI >= 4) was
      higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15
      pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67],
      respectively); and smokers had increasing risk of BASDAI >= 4 with increasing
      years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008
      and 0.006, respectively). The risk of having active disease was higher in
      patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74
      [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of
      cigarettes per day and pack-years. Smokers had an increased risk of BASFI >= 4 (p
      trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and
      ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10
      [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16,
      0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non
      smokers. Smoking is a risk factor for greater disease activity and worse
      functioning in AS patients.

PMID- 29589134
TI  - The relationship between HPV status and chemoradiotherapy in the locoregional
      control of penile cancer.
AB  - BACKGROUND: Penile cancer (PeCa) is a rare, aggressive malignancy often
      associated with the human papillomavirus (HPV). The practice of a personalized
      risk-adapted approach is not yet established. This study is to assess the
      relationship between HPV tumor status and chemoradiotherapy (CRT) in PeCa
      locoregional control (LRC). METHODS: We retrospectively identified patients with
      HPV status who were diagnosed with squamous cell carcinoma of the penis and
      treated with surgical resection between 1999 and 2016. The relationship between
      tumor/treatment characteristics and LRC were analyzed with univariate and
      multivariate Cox proportional hazard regression analysis (UVA and MVA,
      respectively). Time-to-event outcomes were estimated with Kaplan-Meier curves and
      compared via log-rank tests. RESULTS: Fifty-one patients were identified. The
      median follow-up was 36.6 months. Patients were primarily HPV-negative (HPV-) (n
      = 28, 55%), and pathologic node positive (pN+) (55%). The 2 year LRC rate was
      54%. pN+ patients had a significantly lower 2 year LRC (37 vs. 81%, p = 0.002).
      In the subgroup analysis of pN+ patients (n = 28), there was a LRC benefit
      associated with the addition of CRT (HR 0.19; 95% CI 0.05-0.70, p = 0.012) and
      HPV-positive (HPV+) disease (HR 0.18; 95% CI 0.039-0.80, p = 0.024) using MVA.
      HPV+ patients treated with CRT had improved 2 year LRC compared to HPV- patients
      (83 vs. 38%, p = 0.038). CONCLUSIONS: Adjuvant CRT and HPV+ disease independently
      predicted for improved LRC in pN+ PeCa. In HPV+ PeCa, the LRC benefit was
      primarily observed in patients treated with adjuvant CRT. Prospective
      investigation of HPV+ and CRT is required to further delineate their roles in
      optimizing PeCa treatment.

PMID- 29589135
TI  - Safety and effectiveness of umbilical hernia repair in patients with cirrhosis.
AB  - PURPOSE: Umbilical hernia is a common complication in patients with cirrhosis.
      Early studies have reported a high morbidity and mortality associated with hernia
      repair. The traditional approach has been to non-operatively manage umbilical
      hernias in patients with cirrhosis. There are emerging data suggesting that an
      elective repair is a preferable approach. This study examined the outcomes of
      umbilical hernia repair in patients with advanced liver disease and compared this
      with a control group of non-cirrhotic patients. METHODS: Prospective data were
      collected regarding the outcome of umbilical hernia repairs performed between
      2004 and 2013 at the Austin Hospital, Melbourne, Australia. Outcomes at 90 days
      were compared between patients with and without cirrhosis. RESULTS: 79 patients
      with cirrhosis and 249 controls were analysed. Of the patients with cirrhosis, 9%
      were classified as Child-Pugh A, 61% were Child-Pugh B and 30% were Child-Pugh C.
      Emergency repairs for complicated hernias was undertaken in 18% of the cirrhosis
      population and 10% in controls (P = 0.10). Post-operative complications occurred
      more commonly in patients with cirrhosis (26%) compared with controls (11%) (P <
      0.01). Emergency hernia repairs were associated with a higher complication rate
      in both patients with cirrhosis (62%) and controls (20%) (P = 0.01). There was no
      significant difference in the rate of hernia recurrence as assessed by clinical
      examination between patients with cirrhosis (2.7%) and controls (6.8%) (P = 0.17)
      nor in 90-day mortality between patients with cirrhosis (n = 1, 1.3%) and the
      controls (n = 0) (P = 0.43). CONCLUSIONS: Within the limitations of a small study
      cohort and therefore an underpowered study, elective surgical repair of umbilical
      hernias in patients with cirrhosis, including decompensated cirrhosis, may not be
      associated with a significant increase in mortality when compared to a control
      cohort. Whilst complications are higher in cirrhotic patients, there is no
      difference in the rate of hernia recurrence. Emergency repairs of umbilical
      hernias are associated with a high complication rate in cirrhotic patients.

PMID- 29589136
TI  - Syndemic Conditions, HIV Transmission Risk Behavior, and Transactional Sex Among
      Transgender Women.
AB  - This study examined the effect of four syndemic conditions-namely, polydrug use,
      depression, childhood sexual abuse, and intimate partner violence-on rates of HIV
      transmission risk behavior (TRB) and separately, transactional sex among
      transgender women. TRB was defined as the number of condomless penetrative sex
      events with a casual or main partner of discordant or unknown HIV status. Using
      data from 212 transgender women in New York City, multivariable analyses revealed
      that, compared to those with no syndemic conditions, dramatically higher rates of
      recent HIV TRB events (ARR = 8.84, p < 0.001) and recent transactional sex events
      (ARR = 8.32, p < 0.001) were reported by participants with all four syndemic
      conditions. These findings highlight the importance of considering the role of
      syndemic conditions in HIV risk among transgender women, and the need for
      comprehensive psychosocial interventions to improve sexual health among this
      population.

PMID- 29589137
TI  - Barriers and Facilitators to Oral PrEP Use Among Transgender Women in New York
      City.
AB  - Transgender women may face a disparate risk for HIV/AIDS compared to other
      groups. In 2012, Truvada was approved for daily use as HIV pre-exposure
      prophylaxis (PrEP). However, there is a dearth of research about barriers and
      facilitators to PrEP in transgender women. This paper will shed light on
      transgender women living in New York City's perceived and actual challenges to
      using PrEP and potential strategies to overcome them. After completing an initial
      screening process, four 90-min focus groups were completed with n = 18
      transgender women. Participants were asked what they like and dislike about PrEP.
      Participants identified the following barriers: uncomfortable side effects,
      difficulty taking pills, stigma, exclusion of transgender women in advertising,
      and lack of research on transgender women and PrEP. Facilitators included:
      reducing pill size, increasing the types of available HIV prevention products,
      and conducting scientific studies to evaluate PrEP in transgender women.

PMID- 29589138
TI  - Mutational analysis of triple-negative breast cancers within the International
      Breast Cancer Study Group (IBCSG) Trial 22-00.
AB  - PURPOSE: We investigated the occurrence and the prognostic and predictive
      relationship of a selected number of somatic mutations in triple-negative breast
      cancer (TNBC) patients having known clinical outcomes treated within the IBCSG
      Trial 22-00. METHODS: A matched case-control sampling selected patients enrolled
      in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases
      had invasive breast cancer recurrence (at local, regional, or distant site)
      according to the protocol definition. Matched controls had not recurred.
      Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array
      System. The panel includes 19 genes belonging to different functional pathways as
      PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group.
      Conditional logistic regression assessed the association of mutation status with
      breast cancer recurrence. RESULTS: Mutation assessment was successful for 135
      patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had
      at least one mutation in the selected genes. PIK3CA was the most common mutated
      gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and
      AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds
      of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28;
      95% CI 0.88-5.92), though this difference was not statistically significant (p =
      0.09). We found no evidence that these mutations were predictive for the value of
      maintenance metronomic chemotherapy. CONCLUSIONS: Mutations in the tested
      oncogenes were not associated with breast cancer recurrence in this TNBC subset
      of patients. The question of whether any of these mutated genes (e.g., PIK3CA)
      may represent a useful therapeutic target in TNBC may be answered by ongoing
      clinical trials and/or larger dataset analysis.

PMID- 29589139
TI  - Fish Community Structure and Diet Responses to Newbury Weirs in a Low-Gradient
      River.
AB  - Restoration projects are often implemented to address specific issues in the
      environment. Consequences of a restoration project, if any are measured,
      typically focus on direct changes to the projects focus. However, changing
      habitat structure likely results in changes to the environment that affect the
      communities living there. Rock weirs have been used for channel stabilization in
      many midwestern rivers. Previous research in a southern Illinois river found that
      weirs benefitted aquatic macroinvertebrate and riparian bird communities by
      enhancing habitat heterogeneity and insect emergence production. We hypothesized
      that fishes would also benefit from weirs through enhanced habitat and food
      availability. We collected fishes in the Cache River in southern Illinois using
      hand nets, seines, and electroshocking at sites where weirs had been installed
      and at non-weir sites. Gut contents were identified and individual food items
      measured. Fish species richness, but not diversity, was higher at weir sites.
      Fish communities also differed between site types, with benthic feeders
      characterizing weir sites. Gut content biomass and abundance differed among fish
      guilds but not between weir and non-weir sites. Fishes from both site types
      selected for prey taxa predominately found at weirs. Differences between site
      types were not always captured by univariate metrics, but connecting fish prey to
      habitat suggests a reach-scale benefit for fishes through increased abundance of
      favored prey and enhanced prey diversity. Additionally, given the paucity of
      rocky substrata in the river as a whole, rock weirs enhance fish species richness
      by providing habitat for less common benthic species.

PMID- 29589140
TI  - Systematic review of tonsil surgery quality registers and introduction of the
      Nordic Tonsil Surgery Register Collaboration.
AB  - PURPOSE: Surgical quality registers provide tools to measure and improve the
      outcome of surgery. International register collaboration creates an opportunity
      to assess and critically evaluate national practices, and increases the size of
      available datasets. Even though millions of yearly tonsillectomies and
      tonsillotomies are performed worldwide, clinical practices are variable and
      inconsistency of evidence regarding the best clinical practice exists. The need
      for quality improvement actions is evident. We aimed to systematically
      investigate the existing tonsil surgery quality registers found in the
      literature, and to provide a thorough presentation of the planned Nordic Tonsil
      Surgery Register Collaboration. METHODS: A systematic literature search of
      MEDLINE and EMBASE databases (from January 1990 to December 2016) was conducted
      to identify registers, databases, quality improvement programs or comprehensive
      audit programs addressing tonsil surgery. RESULTS: We identified two active
      registers and three completed audit programs focusing on tonsil surgery quality
      registration. Recorded variables were fairly similar, but considerable variation
      in coverage, number of operations included and length of time period for
      inclusion was discovered. CONCLUSION: Considering tonsillectomies and
      tonsillotomies being among the most commonly performed surgical procedures in
      otorhinolaryngology, it is surprising that only two active registers could be
      identified. We present a Nordic Tonsil Surgery Register Collaboration-an
      international tonsil surgery quality register project aiming to provide accurate
      benchmarks and enhance the quality of tonsil surgery in Denmark, Finland, Norway
      and Sweden.

PMID- 29589141
TI  - Highlights from the Second International Symposium on HPV infection in head and
      neck cancer.
AB  - The Second International Symposium on HPV Infection in Head and Neck Cancer was
      held on 3rd-4th November 2016 in Leipzig, Germany. The meeting brought together
      researchers and clinicians to share the latest knowledge on HPV infection in head
      and neck cancer and to join active and constructive scientific discussions. This
      report summarizes the major themes discussed during the symposium.

PMID- 29589144
TI  - Changes in tree resistance, recovery and resilience across three successive
      extreme droughts in the northeast Iberian Peninsula.
AB  - Understanding which variables affect forest resilience to extreme drought is key
      to predict future dynamics under ongoing climate change. In this study, we
      analyzed how tree resistance, recovery and resilience to drought have changed
      along three consecutive droughts and how they were affected by species, tree
      size, plot basal area (as a proxy for competition) and climate. We focused on the
      three most abundant pine species in the northeast Iberian Peninsula: Pinus
      halepensis, P. nigra and P. sylvestris during the three most extreme droughts
      recorded in the period 1951-2010 (occurred in 1986, 1994, and 2005-2006). We
      cored trees from permanent sample plots and used dendrochronological techniques
      to estimate resistance (ability to maintain growth level during drought),
      recovery (growth increase after drought) and resilience (capacity to recover pre
      drought growth levels) in terms of tree stem basal area increment. Mixed-effects
      models were used to determine which tree- and plot-level variables were the main
      determinants of resistance, recovery and resilience, and to test for differences
      among the studied droughts. Larger trees were significantly less resistant and
      resilient. Plot basal area effects were only observed for resilience, with a
      negative impact only during the last drought. Resistance, recovery and resilience
      differed across the studied drought events, so that the studied populations
      became less resistant, less resilient and recovered worse during the last two
      droughts. This pattern suggests an increased vulnerability to drought after
      successive drought episodes.

PMID- 29589143
TI  - The multiplanar analysis of the retromandibular vein in surgical planning for
      parotid gland tumors.
AB  - OBJECTIVE: To analyze the effectiveness of the multiplanar analysis of the
      retromandibular vein in establishing the position of the parotid gland tumor and
      its relationship with the facial nerve, together with the most common
      radiological criteria (facial nerve line, Utrecht line, retromandibular vein and
      parapharyngeal space variations) using the magnetic resonance imaging. STUDY
      DESIGN: Retrospective study SETTING: Tertiary Academic Hospital SUBJECTS AND
      METHODS: 128 preoperative magnetic resonances were analyzed to study preoperative
      tumor location (medial or lateral to the expected course of the facial nerve)
      based on comparison between the radiological criteria and the surgical findings.
      RESULTS: FN line had the lowest accuracy at 77%, whereas the retromandibular vein
      achieved 85% accuracy and the UT line achieved accuracy of 93%. The
      retromandibular vein could not be identified in 11 cases (9%). The multiplanar
      evaluation of the retromandibular vein allowed us to identify it on almost all MR
      images (99% of cases) and reach 87% of accuracy. The parapharyngeal space
      evaluation achieved 92% of accuracy. In the subgroup of 66 cases where the
      neoplasms were strictly related to the main trunk, where the surgery entailed
      manipulation if situated laterally to the tumor, the multiplanar evaluation of
      the retromandibular vein reached 98% of accuracy and UT line achieved 94%.
      CONCLUSIONS: The multiplanar modality, combined with the evaluation of the
      parapharyngeal space, is effective in helping the surgeon to achieve accurate
      planning: it enables the tumor to be located and the facial nerve course
      predicted with a good precision.

PMID- 29589142
TI  - Prognostic values of hematological biomarkers in nasopharyngeal carcinoma
      patients treated with intensity-modulated radiotherapy.
AB  - PURPOSE: In this study, we evaluated the prognostic values of hematological
      biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving
      definitive intensity-modulated radiotherapy (IMRT). METHODS: There were 427 NPC
      patients enrolled between January 2010 and March 2013 at Fudan University
      Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet
      count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and
      platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The
      Kaplan-Meier method and log-rank test were utilized to calculate progression-free
      survival (PFS) and overall survival (OS). The Cox proportional hazard models were
      applied to assess variables. RESULTS: ANC, APC and ALC were declined, while NLR
      and PLR were elevated significantly after therapy (P < 0.001 each). On
      multivariate analysis, pre-treatment NLR >= 2.32 was associated with shortened OS
      (P = 0.048) and PFS (P = 0.008), whereas PLR >= 123.0 was related with inferior
      OS (P = 0.032), yet it was not correlated with PFS (P = 0.161). CONCLUSIONS: High
      pre-treatment NLR and PLR indicated poor survival in NPC patients treated with
      IMRT-based therapy. As easily accessible and economically feasible biomarkers,
      NLR and PLR can be applied into clinical practice, in combination with current
      TNM staging, to design a more personalized treatment in these patients.

PMID- 29589145
TI  - Anatomical description of the umbilical arteries and impact of their ligation on
      pelvic and perineal vascular supply after cystectomy in women.
AB  - OBJECTIVE: In radical cystectomy, the surgeon generally ligates the umbilical
      artery at its origin. This artery may give rise to several arteries that supply
      the sexual organs. Our aim was to evaluate pelvic and perineal devascularisation
      in women after total cystectomy. PATIENTS AND METHODS: We carried out a
      prospective anatomical and radiological study. We performed bilateral pelvic
      dissections of fresh adult female cadavers to identify the dividing branches of
      the umbilical artery. In parallel, we examined and compared the pre- and
      postoperative imaging investigations [magnetic resonance imaging (MRI)
      angiography] in patients undergoing cystectomy for benign disease to quantify the
      loss of pelvic vascularisation on the postoperative images by identifying the
      occluded arteries. RESULTS: The anatomical study together with the radiological
      study visualised 35 umbilical arteries (n = 70) with their branching patterns and
      collateral arteries. The uterine artery originated from the umbilical artery in
      more than 75% of cases (n = 54) of the internal pudendal artery in 34% (n = 24)
      and the vaginal artery in 43% (n = 30). The postoperative MRI angiograms showed
      pelvic devascularisation in four patients. Devascularisation was dependent on the
      level of surgical ligation. In the four patients with loss of pelvic vascular
      supply, the umbilical artery had been ligated at its origin. CONCLUSION: The
      umbilical artery gives rise to various branches that supply the pelvis and
      perineum. If the surgeon ligates the umbilical artery at its origin during total
      cystectomy, there is a significant risk of pelvic and perineal devascularisation.

PMID- 29589146
TI  - Ectopic expression of VpSTS29, a stilbene synthase gene from Vitis
      pseudoreticulata, indicates STS presence in cytosolic oil bodies.
AB  - MAIN CONCLUSION: Stilbene synthase (STS) and its metabolic products are
      accumulated in senescing grapevine leaves. Ectopic expression of VpSTS29 in
      Arabidopsis shows the presence of VpSTS29 in oil bodies and increases trans
      piceid in developing leaves. Stilbenes are the natural antimicrobial phytoalexins
      that are synthesised via the phenylpropanoid pathway. STS is the key enzyme
      catalysing the production of stilbenes. We have previously reported that the
      VpSTS29 gene plays an important role in powdery mildew resistance in Vitis
      pseudoreticulata. However, the synthesis and accumulation of these stilbene
      products in plant cells remain unclear. Here, we demonstrate that VpSTS29 is
      present in cytosolic oil bodies and can be transported into the vacuole at
      particular plant-developmental stages. Western blot and high-performance liquid
      chromatography showed that STS and trans-piceid accumulated in senescent grape
      leaves and in pVpSTS29::VpSTS29-expressing Arabidopsis during age-dependent leaf
      senescence. Subcellular localisation analyses indicated VpSTS29-GFP was present
      in the cytoplasm and in STS-containing bodies in Arabidopsis. Nile red staining,
      co-localisation and immunohistochemistry analyses of leaves confirmed that the
      STS-containing bodies were oil bodies and that these moved randomly in the
      cytoplasm and vacuole. Detection of protein profiles revealed that no free GFP
      was detected in the pVpSTS29::VpSTS29-GFP-expressing protoplasts or in
      Arabidopsis during the dark-light cycle, demonstrating that GFP fluorescence
      distributed in the STS-containing bodies and vacuole was the VpSTS29-GFP fusion
      protein. Intriguingly, in comparison to the controls, over-expression of VpSTS29
      in Arabidopsis resulted in relatively high levels of trans-piceid, chlorophyll
      content and of photochemical efficiency accompanied by delayed leaf senescence.
      These results provide exciting new insights into the subcellular localisation of
      STS in plant cells and information about stilbene synthesis and storage.

PMID- 29589148
TI  - [Trabeculectomy with mitomycin C : Video article].
AB  - Trabeculectomy is the most proven method for the treatment of open angle
      glaucoma. The long-term results of this method show an 80% success rate in
      lowering intraocular pressure over 20 years. The surgical technique is
      demonstrated in detail with the help of a video of the operation and which is
      available online. For more than 15 years trabeculectomy has been performed with
      the use of antifibrotic substances, such as mitomycin C. Long-term treatment with
      antiglaucoma eyedrops leads to a proven inflammation of the conjunctiva and the
      ocular surface with an increase in lymphocytes, mast cells, and fibroblasts.
      Discontinuation of antiglaucoma therapy in turn allows regeneration of the ocular
      surface. From the knowledge gained from these histopathological studies it has
      been recommended to stop glaucoma treatment prior to glaucoma surgery and to
      pretreat the conjunctiva with eyedrops containing cortisone. Administration of
      nonsteroidal antiphlogistic substances or local steroids to the conjunctiva 4
      weeks prior to surgery increases long-term success of the filtering bleb
      function.

PMID- 29589147
TI  - [Primary vitreoretinal lymphoma].
AB  - Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma. It
      is a high grade malignant B-cell lymphoma, which is thought to arise in the
      retina. It often infiltrates the central nervous system (CNS) and is therefore
      associated with a poor prognosis. The PVRL must be differentiated from other
      forms of intraocular lymphoma, such as the low-grade B-cell lymphoma that rarely
      arises in the choroid. The choroidal lymphomas do not spread to the brain, they
      can be treated with low-dose external beam radiotherapy and the patients have a
      good prognosis. Since PVRL is a relatively rare tumor, there is little
      information with respect to its true incidence, to any geographical or ethnic
      variability and to the main risk factors apart from an association with
      immunosuppression, as a result of HIV or Epstein-Barr virus infections. The
      treatment of PVRL is very variable between oncology centres and is also dependent
      on the unilaterality or bilaterality of disease and whether there is any
      concomitant CNS involvement. Further studies and research projects in this field
      are necessary in order to diagnose PVRL at an early stage and to develop new
      targeted individualized treatment.

PMID- 29589149
TI  - [Emigration-an option for African resident physicians? : Opinions from Tanzania
      and Ethiopia].
AB  - BACKGROUND: Globally, the majority of visually impaired persons live in low- and
      middle-income countries. One of the reasons is a lack of ophthalmologists in the
      respective countries. Migration of qualified personnel would be an additional
      strain on ophthalmological patient care. OBJECTIVE: This analysis aimed at
      evaluating the attitude of African residents in ophthalmology towards working in
      their home country or migrating abroad and comparing these findings with existing
      data also with respect to possible interventions. MATERIAL AND METHODS: In 2016
      and 2017, participants of ophthalmological training courses for residents in Dar
      es Salaam (Tanzania) and Addis Ababa (Ethiopia) as well as residents from Moshi
      (Tanzania) were interviewed on possible migration with the help of a
      questionnaire. RESULTS: In total 60 questionnaires were analyzed. The main
      reasons for staying in the home country were: "want to support/serve community",
      "family" as well as "high demand of specialists". Prime motives for possible
      migration were: "better income", "better working structure/equipment" and "better
      education". CONCLUSION: Links between German and African eye hospitals as they
      are supported, for example by the working group International Ophthalmology of
      the German Ophthalmological Society (DOG) and the German Committee for the
      Prevention of Blindness (DKVB), can contribute to improve some of the main
      reasons of migration, such as insufficient education, working structures and
      equipment and thus help to prevent a brain drain.

PMID- 29589150
TI  - Assessment of the pollution and ecological risk of lead and cadmium in soils.
AB  - The aim of the study was to assess the content, distribution, soil binding
      capacity, and ecological risk of cadmium and lead in the soils of Malopolska
      (South Poland). The investigation of 320 soil samples from differently used land
      (grassland, arable land, forest, wasteland) revealed a very high variation in the
      metal content in the soils. The pollution of soils with cadmium and lead is
      moderate. Generally, a point source of lead and cadmium pollution was noted in
      the study area. The highest content of cadmium and lead was found in the
      northwestern part of the area-the industrial zones (mining and metallurgical
      activity). These findings are confirmed by the arrangement of semivariogram
      surfaces and bivariate Moran's correlation coefficients. Among the different
      types of land use, forest soils had by far the highest mean content of
      bioavailable forms of both metals. The results showed a higher soil binding
      capacity for lead than for cadmium. However, for both metals, extremely high
      (class 5) accumulation capacities were dominant. Based on the results, the
      investigated soils had a low (Pb) and moderate (Cd) ecological risk on living
      components. Soil properties, such as organic C, pH, sand, silt, and clay content,
      correlated with the content of total and bioavailable forms of metals in the
      soils. The correlations, despite being statistically significant, were
      characterized by very low values of correlation coefficient (r = 0.12-0.20, at p
      <= 0.05). Therefore, the obtained data do not allow to define any conclusions as
      to the relationships between these soil properties. However, it must be
      highlighted that there was a very strong positive correlation between the total
      content of cadmium and lead and their bioavailable forms in the soils.

PMID- 29589151
TI  - EACR-MRS conference on Seed and Soil: In Vivo Models of Metastasis.
AB  - New experimental tools are urgently required to better understand the metastatic
      process. The importance of such tools is underscored by the fact that many anti
      cancer therapies are generally ineffective against established metastases. This
      makes a major contribution to the fact that metastatic spread is responsible for
      over 90% of cancer patient deaths. It was therefore timely that the recent "Seed
      and Soil: In Vivo Models of Metastasis" conference held in Berlin, Germany (27-29
      of November 2017) aimed to give an in-depth overview of the latest research
      models and tools for studying metastasis, and to showcase recent findings from
      world-leading metastasis researchers. This Meeting Report summarises the major
      themes of this ground-breaking conference.

PMID- 29589152
TI  - Genetic test utilization and diagnostic yield in adult patients with neurological
      disorders.
AB  - To determine the diagnostic yield of different genetic test modalities in adult
      patients with neurological disorders, we evaluated all adult patients seen for
      genetic diagnostic evaluation in the outpatient neurology practice at the
      University of Pennsylvania between January 2016 and April 2017 as part of the
      newly created Penn Neurogenetics Program. Subjects were identified through our
      electronic medical system as those evaluated by the Program's single clinical
      genetic counselor in that period. A total of 377 patients were evaluated by the
      Penn Neurogenetics Program in different settings and genetic testing recommended.
      Of those, 182 (48%) were seen in subspecialty clinic setting and 195 (52%) in a
      General Neurogenetics Clinic. Genetic testing was completed in over 80% of
      patients in whom it was recommended. The diagnostic yield was 32% across disease
      groups. Stratified by testing modality, the yield was highest with directed
      testing (50%) and array comparative genomic hybridization (45%), followed by gene
      panels and exome testing (25% each). In conclusion, genetic testing can be
      successfully requested in clinic in a large majority of adult patients. Age is
      not a limiting factor for a genetic diagnostic evaluation and the yield of
      clinical testing across phenotypes (almost 30%) is consistent with previous
      phenotype-focused or research-based studies. These results should inform the
      development of specific guidelines for clinical testing and serve as evidence to
      improve reimbursement by insurance payers.

PMID- 29589153
TI  - An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in
      Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER).
AB  - BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors,
      which are anti-diabetic drugs, reportedly decrease the incidence of
      cardiovascular events in high-risk patients with cardiovascular diseases, and
      thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in
      patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of
      not only chronic kidney disease but also cardiovascular events, we hypothesized
      that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of
      albuminuria and also improve CHF concomitantly. METHODS: DAPPER (UMIN000025102)
      is a multicenter, randomized, open-labeled, parallel-group, standard treatment
      controlled study, which is designed to evaluate whether dapagliflozin, one of the
      SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts
      cardioprotective effects on the failing heart. The patients are randomized to
      either of the dapagliflozin (5 or 10 mg, once daily orally) or control group
      (administration of anti-diabetic drugs administered other than SGLT 2
      inhibitors). The estimated number of patients that need to be enrolled is 446 in
      total (223 in each group). The primary objective is the changes in the urinary
      albumin-to-creatinine ratio from the baseline after 2-year treatment. The key
      secondary objectives are (1) the safety of dapagliflozin and (2) the
      cardiovascular and renal efficacies of dapagliflozin. CONCLUSION AND
      PERSPECTIVES: DAPPER study investigates whether dapagliflozin decreases
      albuminuria and exerts beneficial effects on the failing heart in T2D patients.
      (UMIN000025102).

PMID- 29589154
TI  - Identification of curable high-risk prostate cancer using radical prostatectomy
      alone: who are the good candidates for undergoing radical prostatectomy among
      patients with high-risk prostate cancer?
AB  - BACKGROUND: Currently, there is no consensus regarding which patients with high
      risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP).
      We aimed to identify patients with high-risk PCa who are treatable by RP alone.
      METHODS: We retrospectively reviewed data on 315 patients with D'Amico high-risk
      PCa who were treated using RP without neoadjuvant or adjuvant therapy at the
      institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The
      primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk
      factors for biochemical progression were extracted using the Cox proportional
      hazard model. We stratified the patients with high-risk PCa into 3 subgroups
      based on bPFS after RP using the risk factors. RESULTS: At a median follow-up of
      49.9 months, biochemical progression was observed in 20.5% of the patients. The 2
      and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate
      analysis, Gleason score (GS) at biopsy (>= 8, HR 1.92, p < 0.05) and % positive
      core (>= 30%, HR 2.85, p < 0.005) were independent predictors of biochemical
      progression. Patients were stratified into favorable- (0 risk factor; 117
      patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk
      factors; 57 patients) risk groups, based on the number of predictive factors. On
      the Cox proportional hazard model, this risk classification model could
      significantly predict biochemical progression after RP (favorable-risk, HR 1.0;
      intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001). CONCLUSION: The risk
      of biochemical progression of high-risk PCa after RP could be stratified by GS at
      biopsy (>= 8) and % positive core (>= 30%).

PMID- 29589155
TI  - Accuracy of tumor segmentation from multi-parametric prostate MRI and 18F-choline
      PET/CT for focal prostate cancer therapy applications.
AB  - BACKGROUND: The study aims to assess the accuracy of multi-parametric prostate
      MRI (mpMRI) and 18F-choline PET/CT in tumor segmentation for clinically
      significant prostate cancer. 18F-choline PET/CT and 3 T mpMRI were performed in
      10 prospective subjects prior to prostatectomy. All subjects had a single biopsy
      confirmed focus of Gleason >= 3+4 cancer. Two radiologists (readers 1 and 2)
      determined tumor boundaries based on in vivo mpMRI sequences, with clinical and
      pathologic data available. 18F-choline PET data were co-registered to T2-weighted
      3D sequences and a semi-automatic segmentation routine was used to define tumor
      volumes. Registration of whole-mount surgical pathology to in vivo imaging was
      conducted utilizing two ex vivo prostate specimen MRIs, followed by gross
      sectioning of the specimens within a custom-made 3D-printed plastic mold. Overlap
      and similarity coefficients of manual segmentations (seg1, seg2) and 18F-choline
      based segmented lesions (seg3) were compared to the pathologic reference
      standard. RESULTS: All segmentation methods greatly underestimated the true tumor
      volumes. Human readers (seg1, seg2) and the PET-based segmentation (seg3)
      underestimated an average of 79, 80, and 58% of the tumor volumes, respectively.
      Combining segmentation volumes (union of seg1, seg2, seg3 = seg4) decreased the
      mean underestimated tumor volume to 42% of the true tumor volume. When using the
      combined segmentation with 5 mm contour expansion, the mean underestimated tumor
      volume was significantly reduced to 0.03 +/- 0.05 mL (2.04 +/- 2.84%).
      Substantial safety margins up to 11-15 mm were needed to include all tumors when
      the initial segmentation boundaries were drawn by human readers or the semi
      automated 18F-choline segmentation tool. Combining MR-based human segmentations
      with the metabolic information based on 18F-choline PET reduced the necessary
      safety margin to a maximum of 9 mm to cover all tumors entirely. CONCLUSIONS: To
      improve the outcome of focal therapies for significant prostate cancer, it is
      imperative to recognize the full extent of the underestimation of tumor volumes
      by mpMRI. Combining metabolic information from 18F-choline with MRI-based
      segmentation can improve tumor coverage. However, this approach requires
      confirmation in further clinical studies.

PMID- 29589156
TI  - Effects of non-surgical periodontal therapy on periodontal laboratory and
      clinical data as well as on disease activity in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: To compare the effect of non-surgical periodontal therapy on clinical
      and inflammatory parameters in patients with moderate to severe chronic
      periodontitis (CP) and rheumatoid arthritis (RA) (RA-CP) with that in CP patients
      without RA. MATERIAL AND METHODS: Eighteen patients with RA-CP and 18
      systemically healthy patients with CP were treated with scaling and root planing
      (SRP) within 24 h. At baseline, and at 3 and 6 months after SRP, clinical
      periodontal parameters, inflammatory markers, and microorganisms in subgingival
      biofilm were assessed. In addition, disease activity markers of RA (DAS28, CRP,
      ESR) and specific antibodies (RF) were monitored in the RA-CP group. RESULTS: In
      both groups, non-surgical therapy yielded to statistically significant
      improvements in all investigated clinical periodontal variables; in RA patients,
      a statistically significant decrease in serum-CRP was seen at 3 months. At all
      time-points, levels of inflammatory markers in GCF were higher in RA-CP than in
      CP patients. Counts of Porphyromonas gingivalis, Tannerella forsythia, and
      Treponema denticola decreased statistically significantly in CP but not in the RA
      CP group. Changes of DAS28 correlated positively with those of P. gingivalis and
      negatively with the plaque index. CONCLUSIONS: Within their limits, the present
      data suggest that (a) non-surgical periodontal therapy improves periodontal
      conditions in CP patients with and without RA and (b) in patients with RA,
      eradication of P. gingivalis in conjunction with a high level oral hygiene may
      transiently decrease disease activity of RA. CLINICAL RELEVANCE: In patients with
      RA and CP, non-surgical periodontal therapy is a relevant modality not only to
      improve the periodontal condition but also to decrease RA activity.

PMID- 29589157
TI  - Association of sleep bruxism with oral health-related quality of life and sleep
      quality.
AB  - OBJECTIVES: To compare the oral health-related quality of life (OHRQoL) and sleep
      quality of subjects with and without sleep bruxism (SB). MATERIALS AND METHODS:
      Participants of both genders were assigned as bruxers (n = 30, age 21-45 years)
      and non-bruxers (n = 30, age 24-40 years). SB was clinically diagnosed and
      confirmed with an electromyography/electrocardiograph portable device (Bruxoff).
      The OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). The sleep
      quality was determined using the Pittsburg Sleep Quality Index (PSQI) and Epworth
      Sleepiness Scale (ESS) questionnaires. OHIP-14, PSQI, and ESS data were analyzed
      by one-way ANOVA, considering a significance level of 5%. RESULTS: Bruxers had
      worse OHRQoL (mean = 16.43) than controls (mean = 4.1), with an effect size (ES)
      of 1.58. Moreover, SB volunteers showed the highest PSQI scores (mean = 7.07; ES
      = 0.82) and excessive daytime sleepiness (mean = 10.33; ES = 0.65), compared to
      non-bruxers (means = 4.7 and 7.8, respectively). CONCLUSIONS: SB may be
      associated with a negative impact on OHRQoL and sleep quality. CLINICAL
      RELEVANCE: Determining that SB may have a marked role in OHRQoL and sleep quality
      is important for dental professionals establish proper multifactorial management,
      and understand patient-related psychosocial aspects.

PMID- 29589158
TI  - Correction to: Model-Based Adaptive Optimal Design (MBAOD) Improves Combination
      Dose Finding Designs: an Example in Oncology.
AB  - The middle initial in the fifth author's name is incorrect in the original
      article. "Lena F. Friberg" should be "Lena E. Friberg". The original article was
      corrected.

PMID- 29589159
TI  - Ten alien chromosome additions of Gossypium hirsutum-Gossypium bickii developed
      by integrative uses of GISH and species-specific SSR markers.
AB  - Gossypium bickii: (2n = 26, G1G1), a wild diploid cotton, carries many favourable
      traits. However, these favourable traits cannot be directly transferred into G.
      hirsutum (2n = 52, AADD) cultivars due to the differences in genomes. Monosomic
      alien addition lines (MAALs) are considered an invaluable tool for the
      introgression of genes of interest from wild relatives into cultivated crops. In
      this study, the G. hirsutum-G. bickii amphidiploid (2n = 78, AADDG1G1) was
      backcrossed with G. hirsutum to develop alien additions containing individual G.
      bickii chromosomes in a G. hirsutum background. Genomic in situ hybridization was
      employed to detect the number of alien chromosomes added to the backcross
      progenies. A total of 183 G. bickii-specific DNA markers were developed to
      discriminate the identities of the G. bickii chromosomes added to G. hirsutum and
      assess the alien chromosome transmissibility. Chromosomes 4Gb and 13Gb showed the
      highest transmissibility, while chromosomes 1Gb, 7Gb and 11Gb showed the lowest.
      Ten of the 13 possible G. hirsutum-G. bickii MAALs were isolated and
      characterized, which will lay the foundation for transferring resistance genes of
      G. bickii into G. hirsutum, as well as for gene assignment, physical mapping, and
      selective isolation and mapping of cDNAs for particular G. bickii chromosomes.
      The strategies of how to use MAALs to develop varieties with the trait of
      interest from wild species (such as glanded plant-glandless seed) were proposed
      and discussed.

PMID- 29589160
TI  - HLA-C*06:02-independent, gender-related association of PSORS1C3 and PSORS1C1/CDSN
      single-nucleotide polymorphisms with risk and severity of psoriasis.
AB  - Psoriasis vulgaris (PsV) is a common, chronic skin disease with a complex genetic
      and environmental etiology. We investigated, in 461 psoriatic patients and 454
      healthy controls, the associations with psoriasis of four single-nucleotide
      polymorphisms (SNPs) from the psoriasis susceptibility 1 (PSORS1) interval:
      rs1062470 (PSORS1C1/CDSN), rs887466 (PSORS1C3), rs2894207 and rs10484554
      (LOC105375015). The minor alleles of three SNPs (rs1062470A, rs2894207C and
      rs10484554T) strongly increased the disease risk (OR = 2.17, p < 0.0001; OR =
      2.33, p < 0.0001 and OR = 2.68, p < 0.0001, respectively), whereas the minor A
      allele of rs887466 exerted a protective effect (OR = 0.73, p = 0.001). The
      strength of association for SNPs was the highest in patients with very early
      onset psoriasis (<= 20 years), while in late onset psoriasis (> 40 years) the
      association was the weakest. The haplotype
      rs1062470A/rs887466G/rs2894207C/rs10484554T highly significantly increased the
      disease risk (OR = 3.58, p = 8.0e-027), while the haplotypes
      rs1062470G/rs887466A/rs2894207T/rs10484554C and
      rs1062470G/rs887466G/rs2894207T/rs10484554C were strongly protective (OR = 0.65,
      p = 0.002 and OR = 0.55, p = 2.4e-009, respectively). Additionally, we showed a
      HLA-C*06:02-independent gender-related effect of the rs887466A allele which was
      protective against psoriasis in males (OR = 0.61, p = 9.2e-005), but not in
      females (p = 0.66). We also demonstrated a correlation of PASI score value with
      rs1062470 genotype, and again only in male patients (p = 0.006) and HLA-C*06:02
      independent. Our results show, for the first time, the male-only associations of
      the PSORS1C3 gene with psoriasis risk and of the PSORS1C1/CDSN gene with severity
      of disease. However, the age dependent associations need to be validated in
      larger sample sizes as well as in other populations.

PMID- 29589161
TI  - Phyllanthus rufuschaneyi: a new nickel hyperaccumulator from Sabah (Borneo
      Island) with potential for tropical agromining.
AB  - BACKGROUND: Nickel hyperaccumulator plants are of much interest for their
      evolution and unique ecophysiology, and also for potential applications in
      agromining-a novel technology that uses plants to extract valuable metals from
      soil. The majority of nickel hyperaccumulators are known from ultramafic soils in
      tropical regions (Cuba, New Caledonia and Southeast Asia), and one genus,
      Phyllanthus (Phyllanthaceae), is globally the most represented taxonomic entity.
      A number of tropical Phyllanthus-species have the potential to be used as 'metal
      crops' in agromining operations mainly because of their ease in cultivation and
      their ability to attain high nickel concentrations and biomass yields. RESULTS:
      One of the most promising species globally for agromining, is the here newly
      described species Phyllanthus rufuschaneyi. This species can be classified in
      subgenus Gomphidium on account of its staminate nectar disc and pistillate entire
      style and represents the most western species of this diverse group. The flower
      structure indicates that this species is probably pollinated by Epicephala moths.
      CONCLUSIONS: Phyllanthus rufuschaneyi is an extremely rare taxon in the wild,
      restricted to Lompoyou Hill near Kinabalu Park in Sabah, Malaysia. Its
      utilization in agromining will be a mechanism for conservation of the taxon, and
      highlights the importance of habitat and germplasm preservation if rare species
      are to be used in novel green technologies.

PMID- 29589162
TI  - The capsular line reference, a new arthroscopic reference for posterior/anterior
      femoral tunnel positioning in anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Femoral malposition is the first cause for graft rupture during ACL
      reconstruction. Arthroscopic landmarks can be difficult to identify. So, landmark
      has to be found for reliable tunnel placement. A proximal-distal reference was
      described as "Apex reference" reported by Hart et al. but no posterior/anterior
      reference exists in the literature. The purpose of this study was to do a 3D CT
      scan assessment of the femoral tunnel positioning using the Capsular Line
      Reference (CLR) as a landmark for posterior/anterior placement in ACL
      reconstruction. We hypothesized the CLR could provide a precise and reliable
      antero/posterior femoral tunnel positioning less than 2 mm from the Bernard &
      Hertel posterior quarter. METHODS: Seven cadaveric knee specimens with a mean age
      of 79.2 +/- 11 years were used. Using standard approaches, the CLR was identified
      corresponding to a white line (the capsule) appearing at the posterior border of
      the femoral condyle after bony debridement of the medial and posterior part of
      the lateral femoral condyle. The center of the tunnel was marked. An inside-out
      technique with anteromedial drilling technique was performed using an 8-mm
      diameter reamer. The distal femurs were sawed and a CT-scan was done for each
      specimen to obtain 3-dimensional image reconstructions. These 3D reconstructions
      were analyzed to measure the position tunnel center on the posterior/anterior
      axis and the distance from the posterior/anterior quadrant according to the
      Bernard & Hertel method. RESULTS: The mean position for the posterior/anterior
      axis was 27.0 +/- 1.8% (25-28.9) with a median of 26.9%. The position from the
      first quarter of the Bernard & Hertel method was 0.9 +/- 0.8 mm (0-1.8) with a
      median of 0.8 mm. CONCLUSION: The CLR is a reliable and reproducible arthroscopic
      landmark to place the femoral tunnel for ACL reconstruction in the
      anterior/posterior axis. Proximal/distal position depends on the choice of the
      surgeon to reproduce anteromedial or posterolateral fibers.

PMID- 29589164
TI  - Progression Patterns in the Remnant Pancreas after Resection of Non-Invasive or
      Micro-Invasive Intraductal Papillary Mucinous Neoplasms (IPMN).
AB  - BACKGROUND: Although IPMN are thought to represent a whole-gland disease,
      segmental resection remains the most frequently performed treatment. We sought to
      determine the rates, patterns, and predictors of IPMN progression in the
      pancreatic remnant following segmental resection of noninvasive or microinvasive
      IPMN. METHODS: A prospectively maintained database was queried to identify all
      patients who underwent resection of noninvasive or microinvasive IPMN (<= 10 mm
      of invasive component) between 1989 and 2015. Progression (recurrence) was
      defined as either the development of cancer, a new IPMN cystic lesion > 1 cm or
      >= 50% increase in the diameter of residual IPMN lesions in the remnant.
      Univariate and multivariate cox regression models were created to determine
      predictors of progression. RESULTS: A total of 319 patients underwent resection
      for noninvasive and microinvasive IPMN. The median age was 68, 53% had branch
      duct (BD) IPMN, and 6% had microinvasive disease. After a median follow-up of 42
      months, 71 patients (22%) experienced IPMN progression. Within this group of 71
      patients, 11 (16% of recurrence) developed invasive cancer in the pancreatic
      remnant after a median of 28 months. Twelve patients (17%) experienced
      progression > 5 years following initial resection. On multivariate analysis, a
      distal location of the initial lesion was associated with an increased risk of
      progression (multivariate hazards ratio = 2.43, confidence interval 1.47-4.0, p <
      0.001). CONCLUSIONS: In this study, 22% of patients had disease progression
      following resection of noninvasive or microinvasive IPMN; 16% of these
      progressions represented invasive disease. These patients represent a high-risk
      group and should undergo long-term radiographic surveillance.

PMID- 29589163
TI  - Casual Sexual Scripts on the Screen: A Quantitative Content Analysis.
AB  - While existing content analyses have provided insightful information in terms of
      contextual factors and frequency of sexual behaviors, not much is known about the
      relational context in which sexual depictions generally occur. The current study
      addresses this void by employing content analytic methods to measure the
      frequency and context of depictions of sexual behavior within nine popular
      television shows produced in the U.S., while taking into account the type of
      sexual behavior. The results suggest that, in the analyzed television shows,
      sexual behaviors within a casual sexual context were almost as frequently shown
      as sexual behaviors within a committed relationship context. Whereas sexual
      behaviors within a committed relationship context were mainly limited to
      passionate kissing, sexual behaviors within a casual sexual context mostly
      consisted of explicit portrayals of sexual intercourse. Additionally, genre
      seemed to be an important factor when examining casual sexual television content.
      The situational comedy genre, for example, had no explicit portrayals of
      intercourse and mainly portrayed kissing couples within a committed relationship.
      The comedy drama genre, on the contrary, had the largest proportion of explicit
      sexual portrayals, usually between casual sexual partners. A second goal of this
      study was to analyze the portrayals of the typical casual sexual experience
      script and the typical casual sexual relationship script in which these sexual
      behaviors often occur. For instance, our analyses revealed that female characters
      were more likely to initiate casual sex compared to male characters. Moreover,
      casual sex often occurred between former partners.

PMID- 29589165
TI  - Self-Directed Gambling Changes: Trajectory of Problem Gambling Severity in
      Absence of Treatment.
AB  - Most problem gamblers do not seek formal treatment, recovering on their own
      through cognitive re-appraisal or self-help strategies. Although barriers to
      treatment have been extensively studied, there is a paucity of research on self
      directed changes in problem gambling and very few studies have examined these
      changes prospectively. The aim of this study was to examine the trajectory of
      gambling severity and behavior change over an 18-month period, among a sample of
      non-treatment seeking/attending problem gamblers recruited from the community (N
      = 204) interested in quitting or reducing gambling. Separate mixed effects models
      revealed that in absence of formal treatment, significant reductions in gambling
      severity, frequency, and amount gambled could be observed over the course of a 6
      to 9-month period and that changes experienced within the first 12 months were
      maintained for an extended 6 months. Problem gambling severity at baseline was
      significantly associated with changes in severity over time, such that
      participants with more severe gambling problems demonstrated greater reductions
      in their gambling severity over time. A total of 11.1% of participants gambled
      within a low-risk threshold at 18 months, although 28.7% of the sample reported
      consecutive gambling severity scores below problem levels for the duration of 1
      year or longer. The findings suggest that among problem gamblers motivated to
      quit or reduce their gambling, significant self-directed changes in gambling
      severity can occur over a relatively short time. Additional prospective studies
      are needed to document the role of specific self-help tools or thought processes
      in exacting gambling changes.

PMID- 29589166
TI  - Evidence of Skill and Strategy in Daily Fantasy Basketball.
AB  - Using hand-collected data from DraftKings.com, a major daily fantasy sports
      website, we analyze draft selections of thousands of participants in daily
      fantasy basketball (DFB). In our study, the first thorough examination of DFB, we
      show that DFB is a game in which skill is necessary for success. Using
      econometric analysis, we find that winning participants utilize different
      strategies than losing participants; for example, winning participants more
      frequently select NBA rookies and international players. We also find that
      participants paying to enter more lineups in a given contest earn profits far
      more often than those entering few lineups, indicating that the number of lineups
      entered can serve as a proxy for skill. Additionally, we provide a thorough
      discussion of industry characteristics, prior literature, and gameplay, which
      should help readers familiarize themselves with this burgeoning fantasy sports
      variant. This study should further the literature on the contentious activity,
      which has been outlawed in many U.S. states and continues to elicit controversy.

PMID- 29589167
TI  - Cartilage Metabolism is Modulated by Synovial Fluid Through Metalloproteinase
      Activity.
AB  - Synovial fluid (SF) contains various cytokines that regulate chondrocyte
      metabolism and is dynamically associated with joint disease. The objective of
      this study was to investigate the effects of diluted normal SF on catabolic
      metabolism of articular cartilage under inflammatory conditions. For this
      purpose, SF was isolated from healthy bovine joints, diluted, and added to
      cartilage explant cultures stimulated with interleukin-1 (IL-1) for 12 days. The
      kinetic release of sulfated glycosaminoglycan (sGAG) and collagen, as well as
      nitric oxide and gelatinase matrix metalloproteinases were analyzed in the
      supernatant. Chondrocyte survival and matrix integrity in the explants were
      evaluated with Live/Dead and histological staining. Diluted synovial fluid
      treatment suppressed sGAG and collagen release, downregulated the production of
      nitric oxide and matrix metalloproteinases, reduced IL-1-induced chondrocyte
      death, and rescued matrix depletion. Our results demonstrate that normal SF can
      counteract inflammation-driven cartilage catabolism. This study reports on the
      protective function of healthy SF and the therapeutic potential of recapitulation
      of SF for cartilage repair.

PMID- 29589168
TI  - From Tension to Compression: Asymmetric Mechanical Behaviour of Trabecular Bone's
      Organic Phase.
AB  - Trabecular bone is a cellular composite material comprising primarily of mineral
      and organic phases with their content ratio known to change with age. Therefore,
      the contribution of bone constituents on bone's mechanical behaviour, in tension
      and compression, at varying load levels and with changing porosity (which
      increases with age) is of great interest, but remains unknown. We investigated
      the mechanical response of demineralised bone by subjecting a set of bone samples
      to fully reversed cyclic tension-compression loads with varying magnitudes. We
      show that the tension to compression response of the organic phase of trabecular
      bone is asymmetric; it stiffens in tension and undergoes stiffness reduction in
      compression. Our results indicate that demineralised trabecular bone struts
      experience inelastic buckling under compression which causes irreversible damage,
      while irreversible strains due to microcracking are less visible in tension. We
      also identified that the values of this asymmetric mechanical response is
      associated to the original bone volume ratio (BV/TV).

PMID- 29589169
TI  - Polarisation vision: overcoming challenges of working with a property of light we
      barely see.
AB  - In recent years, the study of polarisation vision in animals has seen numerous
      breakthroughs, not just in terms of what is known about the function of this
      sensory ability, but also in the experimental methods by which polarisation can
      be controlled, presented and measured. Once thought to be limited to only a few
      animal species, polarisation sensitivity is now known to be widespread across
      many taxonomic groups, and advances in experimental techniques are, in part,
      responsible for these discoveries. Nevertheless, its study remains challenging,
      perhaps because of our own poor sensitivity to the polarisation of light, but
      equally as a result of the slow spread of new practices and methodological
      innovations within the field. In this review, we introduce the most important
      steps in designing and calibrating polarised stimuli, within the broader context
      of areas of current research and the applications of new techniques to key
      questions. Our aim is to provide a constructive guide to help researchers,
      particularly those with no background in the physics of polarisation, to design
      robust experiments that are free from confounding factors.

PMID- 29589170
TI  - Computerized tests to evaluate recovery of cognitive function after deep sedation
      with propofol and remifentanil for colonoscopy.
AB  - The use of sedation for diagnostic procedures including gastrointestinal
      endoscopy is rapidly growing. Recovery of cognitive function after sedation is
      important because it would be important for most patients to resume safe, normal
      life soon after the procedure. Computerized tests have shown being accurate
      descriptors of cognitive function. The purpose of the present study was to
      evaluate the time course of cognitive function recovery after sedation with
      propofol and remifentanil. A prospective observational double blind clinical
      study conducted in 34 young healthy adults undergoing elective outpatient
      colonoscopy under sedation with the combination of propofol and remifentanil
      using a target controlled infusion system. Cognitive function was measured using
      a validated battery of computerized cognitive tests (CogstateTM, Melbourne,
      Australia) at different predefined times: prior to starting sedation (Tbaseline),
      and then 10 min (T10), 40 min (T40) and 120 min (T120) after the end of
      colonoscopy. Tests included the assessment of psychomotor function, attention,
      visual memory and working memory. All colonoscopies were completed (median time:
      26 min) without significant adverse events. Patients received a median total dose
      of propofol and remifentanil of 149 mg and 98 ug, respectively. Psychomotor
      function and attention declined at T10 but were back to baseline values at T40
      for all patients. The magnitude of psychomotor task reduction was large (d =
      0.81) however 100% of patients were recovered at T40. Memory related tasks were
      not affected 10 min after ending sedation. Cognitive impairment in attention and
      psychomotor function after propofol and remifentanil sedation was significant and
      large and could be easily detected by computerized cognitive tests. Even though,
      patients were fully recovered 40 min after ending the procedure. From a cognitive
      recovery point of view, larger studies should be undertaken to propose adequate
      criteria for discharge after sedation.

PMID- 29589171
TI  - Lowered dose full-spine radiography in pediatric patients with idiopathic
      scoliosis.
AB  - PURPOSE: To optimize our standard full-spine radiography with respect to
      diagnostic quality and dose. METHODS: A phantom study was performed to establish
      an optimal posterior-anterior view (PA) full spine protocol having the lowest
      dose with non-inferior quality compared to standard. We then applied this
      protocol in 40 pediatric patients (group B). The radiographs were scored on six
      criteria by a pediatric radiologist and orthopedist and compared to the scores of
      40 PA full spine radiographs performed in 2013 with standard protocol (group A).
      Radiation dose was assessed by dose area product (DAP) and effective dose (E).
      Statistical analysis included independent samples t test, Mann-Whitney U test and
      intra-class correlation coefficient (ICC). RESULTS: An optimized protocol was
      defined (0.2 mm Cu filter, 0.87 relative exposure, with grid). Mean age was 13.3
      +/- 1.6 years for group A and 13.4 +/- 1.7 years for group B. For group B, the
      mean DAP was 47.0 uGy m2 with an E of 0.13 mSv. For group A, the mean DAP was
      85.3 uGy m2 with an E of 0.24 mSv. This represents a dose reduction of 45%. Mean
      image quality scores for group A (27.9 +/- 2.4) and group B (28.1 +/- 2.3) were
      similar (p = 0.612). Interobserver agreement was observed to be excellent (ICC
      0.92). CONCLUSION: This study demonstrates that a low-dose full-spine radiograph
      can be performed in patients with idiopathic scoliosis without loss of image
      quality. These slides can be retrieved under Electronic Supplementary Material.

PMID- 29589172
TI  - Utilization of phage display to identify antigenic regions in the PCV2 capsid
      protein for the evaluation of serological responses in mice and pigs.
AB  - Porcine circovirus 2 (PCV2) is associated with a series of swine diseases. There
      is a great interest in improving our understanding of the immunology of PCV2,
      especially the properties of the viral capsid protein Cap-PCV2 and how they
      relate to the immunogenicity of the virus and the subsequent development of
      vaccines. Phage display screening has been widely used to study binding
      affinities for target proteins. The aim of this study was to use phage display
      screening to identify antigenic peptides in the PCV2 capsid protein. After the
      selection of peptides, five of them presented similarity to sequences found in
      cap-PCV2, and four peptides were synthesized and used for immunization in mice:
      51-CTFGYTIKRTVT-62 (PS14), 127-CDNFVTKATALTY-138 (PS34), 164-CKPVLDSTIDY-173
      (PC12), and 79-CFLPPGGGSNT-88 (PF1). Inoculation with the PC12 peptide led to the
      highest production of antibodies. Furthermore, we used the PC12 peptide as an
      antigen to examine the humoral response of swine serum by ELISA. The sensitivity
      and specificity of this assay was 88.9% and 92.85%, respectively. Altogether,
      characterization of immunogenic epitopes in the capsid protein of PCV2 may
      contribute to the improvement of vaccines and diagnostics.

PMID- 29589173
TI  - Do dihydroxymagnesium carboxylates form Grignard-type reagents? A theoretical
      investigation on decarboxylative fragmentation.
AB  - Dihydroxymagnesium carboxylates [(OH)2MgO2CR] were probed for decarboxylation on
      a theoretical level, by utilizing both Moller-Plesset perturbation theory (MP2)
      and density functional theory (B3LYP-DFT) computations. This study is connected
      to the question of whether this recently introduced, astrobiologically relevant
      chemical class may form Grignard-type reagent molecules. To extract trends for a
      broad molecular mass range, different linear alkyl chain lengths between C4 and
      C11 were computed. The forward energy barrier for decarboxylation reactions
      increases linearly as a function of the ligand's chain length. Decarboxylation
      type fragmentations of these organomagnesium compounds seem to be improbable in
      non-catalytic, low energetic environments. A high forward energy barrier (EMP2 >
      55 kcal mol-1) towards a described transition state restricts the release of CO2.
      Nevertheless, we propose the release of CO2 on a theoretical level, as been
      revealed via an intramolecular nucleophilic attack mechanism. Once the
      challenging transition state for decarboxylation is overcome, a stable Mg-C bond
      is formed. These mechanistic insights were gained by help of natural bond orbital
      analysis. The Calpha atom (first carbon atom in the ligand chain attached to the
      carboxyl group) is thought to prefer binding towards the electrophilic magnesium
      coordination center, rather than towards the electrophilic CO2-carbon atom.
      Additionally, the putatively formed Grignard-type OH-bearing product molecules
      possess a more polarized Mg-C bond in comparison to RMgCl species. Therefore,
      carbanion formation from OH-bearing Grignard-type molecules is made feasible for
      triggering C-C bond formation reactions. Graphical abstract This study asks
      whether recently introduced, astrobiologically dihydroxymagnesium carboxylates
      form Grignard-type reagent molecules via decarboxylative fragmentation.

PMID- 29589174
TI  - Asking a Variety of Questions on Walk Rounds: a Pilot Study.
AB  - BACKGROUND: Morning walk rounds have lost some of their engagement while
      remaining a useful and valued practice. AIM: We created a pilot study to evaluate
      the impact on rounds of learning to asking a variety of different questions.
      SETTING: One-hour intervention sessions were voluntarily offered to members of
      the Department of Medicine and taught by an expert in the question, listen, and
      respond method. PARTICIPANTS: Participants included attendings and residents in
      Internal Medicine on medical teams. PROGRAM DESCRIPTION: Questionnaires were
      collected on six pre-intervention and six post-intervention days. Nine months
      later, an anonymous online survey was sent to participants asking about their use
      of a wider variety of questions. PROGRAM EVALUATION: Two hundred eight physicians
      (residents 175 (45.5%), attending physicians 25 (27.7%)) filled out pre
      intervention surveys. One hundred eighty-one physicians (residents 155 (40.3%),
      attending physicians 18 (20%)) filled out post-intervention surveys. When survey
      responses from the attendings and residents on the medical teams were combined,
      post-intervention rounds were perceived as more worthwhile (1.99 pre-intervention
      and 1.55 post-intervention, [95% confidence interval 1.831-2.143]) (p < 0.001)
      and more engaging (1.68 pre-intervention and 1.30 post-intervention, [95%
      confidence interval 1.407-1.688]) (p < 0.001).Non-medical teams' survey responses
      did not change. Patient census data indicated no significant difference in the
      hospital's census on the pre- and post-intervention dates. Spontaneous
      suggestions for improving rounds came largely from the residents and included
      teaching points, clinical pearls, patient focus, more interactive, increased
      dedicated time for teaching, inclusive/multidisciplinary, questions, and evidence
      based teaching. Of the participants who answered the online survey 9 months
      later, 75% (6/8) reported that they "actually asked a wider variety of types of
      questions." DISCUSSION: This pilot study indicates that the 1-h intervention of
      learning to ask a variety of different questions is associated with rounds that
      are rated as more worthwhile and engaging by the medical teams.

PMID- 29589175
TI  - Alkyl-Dimethylpyrazines in Mandibular Gland Secretions of Four Odontomachus Ant
      Species (Formicidae: Ponerinae).
AB  - Ponerine ants are known to contain mixtures of pyrazines in their mandibular
      glands. We analyzed the mandibular gland contents of four ponerine species
      (Odontomachus chelifer, O. erythrocephalus, O. ruginodis, and O. bauri) by gas
      chromatography coupled with mass spectrometry, and found that each species
      contains specific mixtures of trisubstituted alkylpyrazines among other
      volatiles. Attempts to identify alkylpyrazines solely by mass spectral
      interpretation is unrealistic because spectra of positional isomers are
      indistinguishable. To avoid misidentifications, we synthesized a large number of
      reference compounds and compared their mass spectral and gas chromatographic
      properties with those present in the Odontomachus species under investigation.
      Most of the compounds identified were 2-alkyl-3,5-dimethylpyrazines.
      Interestingly, when the third substituent was an isopentyl group, the two methyl
      groups were found to be located at the 2 and 5 ring positions. Using our data, we
      recognized several misidentifications in previous publications.

PMID- 29589176
TI  - Photodynamic inactivation in the expression of the Candida albicans genes ALS3,
      HWP1, BCR1, TEC1, CPH1, and EFG1 in biofilms.
AB  - The objective of this study was to evaluate the effects of photodynamic
      inactivation (PDI) on Candida albicans biofilms, evaluating its effects on gene
      expression of ALS3, HWP1, BCR1, TEC1, CPH1, and EFG1 by yeast. Three samples of
      C. albicans were used in this study: a clinical sample from a patient with HIV
      (39S), a clinical sample from a patient with denture stomatitis lesion (Ca30),
      and a standard strain ATCC 18804. The quantification of gene expression was
      related to the production of those genes in the samples referred above using
      quantitative polymerase chain reaction (qPCR) assay in real time. The
      photosensitizer methylene blue at 300 uM and erythrosine at 400 uM, sensitized
      with low-power laser (visible red, 660 nm) and green LED (532 nm), respectively,
      were used for PDI. Four groups of each sample and PDI protocol were evaluated:
      (a) P+L+: sensitization with the photosensitizer and irradiation with light, (b)
      P+L-: only treatment with the photosensitizer, (c) P-L+: only irradiation with
      light, and (d) P-L-: without sensitization with the dye and absence of light. The
      results were analyzed by t test, with a significance level of 5%. The
      photodynamic inactivation was able to reduce the expression of all genes for both
      treatments, laser and LED. The fold-decrease for the genes ALS3, HWP1, BCR1,
      TEC1, CPH1, and EFG1 were 0.73, 0.39, 0.77, 0.71, 0.67, and 0.60 for laser,
      respectively, and 0.66, 0.61, .050, 0.43, 0.54, and 0.66 for LED, respectively.
      It could be concluded that PDI showed a reduction in the expression of C.
      albicans genes, suggesting its virulence decrease.

PMID- 29589178
TI  - Anterior robotic approach in en-bloc sacrectomy: a preliminary experience.
AB  - En-bloc sacrectomy is a highly demanding surgical procedure necessary to obtain
      wide margin in sacral tumor. The double approach, anterior and posterior
      approach, is usually preferred for tumors extending proximally to S3 level where
      iliac internal vessels are at a higher risk for damage during posterior surgery.
      It can be justified also in selected cases to decrease the risk of posterior
      approach as in local recurrence or in patients who already underwent laparotomy.
      Our intent was to apply robotic-assisted techniques for performing anterior
      preparatory approach for sacrectomy surgery. Between December 2010 and December
      2014, three cases of sacrectomies were performed in a previous robotic-assisted
      preparatory approach to separate the rectum from the tumor. Dissections were
      successfully performed in all cases close to the pelvic floor. The surgeon was
      able to position a Gore-Tex spacer between the anterior tumor surface and the
      rectum in all cases. The anterior dissections were performed with a perfect
      control of bleeding. No complications related to the anterior approach were
      reported. Robot-assisted surgery can be considered a valid and minimally invasive
      technique which allows a safe anterior dissection of the pelvic structures
      dividing tumors from surrounding tissues. It allows to place a spacer to protect
      organs during posterior sacral resection performed on the same day or at a later
      time. Further experiences are advocated to evaluate its efficiency in sacral
      tumors of greater size.

PMID- 29589179
TI  - Expression of Hypoxia Inducible Factor 1alpha Is Protein Kinase A-dependent in
      Primary Cortical Astrocytes Exposed to Severe Hypoxia.
AB  - The hypoxia inducible factor 1 (HIF-1) and the cyclic AMP-responsive element
      binding protein (CREB) are two transcription factors that have been studied in
      the context of neuronal survival and neurodegeneration. HIF-1 upregulation and
      CREB activation have been observed not only in neurons but also in astrocytes
      under conditions of hypoxia. We hypothesized that activation of CREB regulate HIF
      1alpha expression in the nucleus of cortical astrocytes under in vitro ischemic
      condition. To test the hypothesis, we determined the effects of inhibiting the
      CREB activation pathway on the expression of HIF-1alpha protein in astrocytes
      exposed to CoCl2 and severe hypoxia (near anoxia, 0.1% O2). The results
      demonstrated that inhibition of CaMKII and CaMKIV had no effect on both HIF
      1alpha and pCREB expression in cortical astrocytes exposed to CoCl2 and anoxia.
      In contrast, PKA inhibition lowered the expression of HIF-1alpha and pCREB
      expression. Furthermore, the inhibition of PKA but not CaMKII or CaMKIV increased
      cell death of astrocytes exposed to near anoxia. The results suggest that PKA
      plays an important role in the cell survival signaling pathways in astrocytes.

PMID- 29589180
TI  - Germline CDH1 mutations are a significant contributor to the high frequency of
      early-onset diffuse gastric cancer cases in New Zealand Maori.
AB  - New Zealand Maori have a considerably higher incidence of gastric cancer compared
      to non-Maori, and are one of the few populations worldwide with a higher
      prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are
      causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome
      primarily characterised by an extreme lifetime risk of developing diffuse gastric
      cancer. Pathogenic CDH1 mutations are well described in Maori families in New
      Zealand. However, the contribution of these mutations to the high incidence of
      gastric cancer is unknown. We have used next-generation sequencing, Sanger
      sequencing, and Multiplex Ligation-dependent Probe Amplification to examine
      germline CDH1 in an unselected series of 94 Maori gastric cancer patients and 200
      healthy matched controls. Overall, 18% of all cases, 34% of cases diagnosed with
      diffuse-type gastric cancer, and 67% of cases diagnosed aged less than 45 years
      carried pathogenic CDH1 mutations. After adjusting for the effect of screening
      known HDGC families, we estimate that 6% of all advanced gastric cancers and 13%
      of all advanced diffuse-type gastric cancers would carry germline CDH1 mutations.
      Our results demonstrate that germline CDH1 mutations are a significant
      contributor to the high frequency of diffuse gastric cancer in New Zealand Maori.

PMID- 29589177
TI  - Time-dependent antimicrobial effect of photodynamic therapy with TONS 504 on
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa (P. aeruginosa) is a major cause of infectious keratitis,
      which itself is a major cause of blindness worldwide. We have now evaluated the
      time-dependent effectiveness of photodynamic antimicrobial chemotherapy (PACT)
      with the chlorin derivative TONS 504 and a light-emitting diode (LED) on P.
      aeruginosa in vitro. PACT with TONS 504 (10 mg/L) and irradiation (30 J/m2) by an
      LED device that delivers light centered on a wavelength of 660 nm was applied to
      1 * 106 colony-forming units of P. aeruginosa in liquid medium. The bacteria were
      then cultured at 37  degrees C for various times before assay of viability by
      determination of colony formation on agar plates. The effect of a second
      irradiation at 3 h after the initial LED exposure was also examined. Bacterial
      growth was markedly inhibited between 3 and 9 h after PACT with TONS 504, with
      the maximal effect being apparent at 3 h. Furthermore, a second exposure to LED
      irradiation at 3 h after the first treatment enhanced the inhibitory effect on
      bacterial growth. PACT with TONS 504 thus inhibited the growth of P. aeruginosa
      in a time-dependent manner, and an additional irradiation exposure applied 3 h
      after the first LED treatment greatly increased the effectiveness of PACT. This
      antibacterial system thus warrants further evaluation with regard to its
      potential effectiveness for the treatment of infectious keratitis.

PMID- 29589181
TI  - Mendelian Susceptibility to Mycobacterial Disease Caused by a Novel Founder IL12B
      Mutation in Saudi Arabia.
AB  - PURPOSE: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare
      primary immunodeficiency predisposing congenitally affected individuals to
      diseases caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guerin
      (BCG) vaccine strains and environmental mycobacteria. IL-12p40 deficiency is a
      genetic etiology of MSMD resulting in impaired IL-12- and IL-23-dependent IFN
      gamma immunity. Most of the reported patients with IL-12p40 deficiency originate
      from Saudi Arabia (30 of 52) and carry the recurrent IL12B mutation c.315insA (27
      of 30). METHODS: Whole-exome sequencing was performed on three patients from two
      unrelated kindreds from Saudi Arabia with disseminated disease caused by a BCG
      vaccine substrain. RESULTS: Genetic analysis revealed a homozygous mutation,
      p.W60X, in exon 3 of the IL12B gene, resulting in complete IL12p40 deficiency.
      This mutation is recurrent due to a new founder effect. CONCLUSIONS: This report
      provides evidence for a second founder effect for recurrent mutations of IL12B in
      Saudi Arabia.

PMID- 29589182
TI  - Isolated acute lupus pneumonitis as the initial presentation of systemic lupus
      erythematosus in an 8-year-old girl.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which has
      broad pleuropulmonary manifestations. One of the rare and mortal complications is
      acute lupus pneumonitis, which is reported very rarely, especially in childhood.
      Herein, we report an 8-year-old girl with isolated acute lupus pneumonitis as the
      initial presentation that required a lung biopsy for diagnosis. Although she had
      improvement with the administration of steroids, steroid treatment was reduced
      due to the drug's side effects resulting in the addition of azathioprine and
      mycophenolate mofetil to the treatment regimen. After the new regimen failed to
      result in clinical improvement, hydroxychloroquine treatment was started and a
      significant improvement was observed. Acute lupus pneumonitis is an uncommon
      manifestation of SLE and diagnosis may be difficult in patients without other
      organ involvement.

PMID- 29589183
TI  - New Diabetes Therapies and Diabetic Kidney Disease Progression: the Role of SGLT
      2 Inhibitors.
AB  - PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have
      emerged as a promising drug class for the treatment of diabetic kidney disease.
      Developed originally as glucose-lowering drugs by enhancing urinary glucose
      excretion, these drugs also lower many other renal and cardiovascular risk
      factors such as body weight, blood pressure, albuminuria, and uric acid. Results
      from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects
      translate into a reduction in cardiovascular outcomes and have the potential to
      delay the progression of kidney function decline. This review summarizes recent
      studies on the mechanisms and rationale of renoprotective effects. RECENT
      FINDINGS: Effects of SGLT-2 inhibitors on the kidney are likely explained by
      multiple pathways. SGLT-2 inhibitors may improve renal oxygenation and intra
      renal inflammation thereby slowing the progression of kidney function decline.
      Additionally, SGLT-2 inhibitors are associated with a reduction in glomerular
      hyperfiltration, an effect which is mediated through increased natriuresis and
      tubuloglomerular feedback and independent of glycemic control. Analogous to
      diabetic kidney disease, various etiologies of non-diabetic kidney disease are
      also characterized by single nephron hyperfiltration and elevated albuminuria.
      This offers the opportunity to reposition SGLT-2 inhibitors from diabetic to non
      diabetic kidney disease. Clinical trials are currently ongoing to characterize
      the efficacy and safety of SGLT-2 inhibitors in patients with diabetic and non
      diabetic kidney disease. The glucose-independent hemodynamic mechanisms of SGLT-2
      inhibitors provide the possibility to extend the use of SGLT-2 inhibitors to non
      diabetic kidney disease. Ongoing dedicated trials have the potential to change
      clinical practice and outlook of high-risk patients with diabetic (and non
      diabetic) kidney disease.

PMID- 29589184
TI  - Controlled Versus Uncontrolled Resistant Hypertension: Are They in the Same Bag?
AB  - PURPOSE OF REVIEW: Resistant hypertension (RHTN) is a condition in which besides
      the antihypertensive therapy using at least three different drugs (including a
      diuretics), brachial blood pressure does not reach the target (e.g., 140/90
      mmHg). RECENT FINDINGS: Despite the diversity of clinical presentations, we
      divide RHTN in two major groups according to blood pressure and number of drugs
      taken: controlled (C-RHTN) and uncontrolled (UC-RHTN) resistant hypertension,
      with refractory hypertension (RfHTN) included in the latter subgroup. Both C-RHTN
      and UC-RHTN are heterogenic and complex syndromes. To better approach this
      matter, the some pathophysiological mechanisms (increased volemia, hyperactivity,
      plasma cortisol, adipocitokines, and other pro-inflammatory factors), have a
      pivotal clinical role. Some features (African ethnic, obesity, age > 60, LV
      hypertrophy, and vascular stiffness) increase the risk of refractoriness as well
      as worst prognosis. Based on increased target organ damage, cardiovascular risk
      and events will be addressed in this review. Our conclusion is that although both
      C-RHTN and UC-RHTN are extreme phenotypes of hard-to-control BP, some mechanisms
      of the disease and clinical expressions are distinct. According to these
      differences, "UC-RHTN and C-RHTN are not in the same bag."

PMID- 29589185
TI  - Contemporary Management of Ulcerative Colitis.
AB  - PURPOSE OF REVIEW: We discuss the newest evidence-based data on management of
      ulcerative colitis (UC). We emphasize risk-stratification, optimizing medical
      therapies, and surgical outcomes of UC. RECENT FINDINGS: Recent medical advances
      include introduction of novel agents for UC. Vedolizumab, an anti-adhesion
      molecule, has demonstrated efficacy in moderate to severe UC. Tofacitinib, a
      small molecule, has also demonstrated efficacy. Data on optimization of
      infliximab show the superiority of combination therapy with azathioprine over
      monotherapy with infliximab or azathioprine alone. Data on anti-tumor necrosis
      factor-alpha (anti-TNF) therapeutic drug monitoring also hold promise, as do
      preliminary data on the dose escalation of infliximab in severe hospitalized UC.
      Surgical outcome data are reassuring, with new fertility data showing the
      effectiveness of in vitro fertilization. UC management is multi-disciplinary and
      changing. While novel therapies hold promise, better optimization of our current
      arsenal will also improve outcomes.

PMID- 29589186
TI  - Protective effects of mitochondrion-targeted peptide SS-31 against hind limb
      ischemia-reperfusion injury.
AB  - Hind limb ischemia-reperfusion injury is an important pathology in vascular
      surgery. Reactive oxygen species are thought to be involved in the pathogenesis
      of hind limb ischemia-reperfusion injury. SS-31, which belongs to a family of
      mitochondrion-targeted peptide antioxidants, was shown to reduce mitochondrial
      reactive oxygen species production. In this study, we investigated whether the
      treatment of SS-31 could protect hind limb from ischemia-reperfusion injury in a
      mouse model. The results showed that SS-31 treatment either before or after
      ischemia exhibited similar protective effects. Histopathologically, SS-31
      treatment prevented the IR-induced histological deterioration compared with the
      corresponding vehicle control. SS-31 treatment diminished oxidative stress
      revealed by the reduced malondialdehyde level and increased activities and
      protein levels of Sod and catalase. Cellular ATP contents and mitochondrial
      membrane potential increased and the level of cytosolic cytC was decreased after
      SS-31 treatment in this IR model, demonstrating that mitochondria were protected.
      The IR-induced increase of levels of inflammatory factors, such as Tnf-alpha and
      Il-1beta, was prevented by SS-31 treatment. In agreement with the reduced
      cytosolic cytC, cleaved-caspase 3 was kept at a very low level after SS-31
      treatment. Overall, the effect of SS-31 treatment before ischemia is mildly more
      effective than that after ischemia. In conclusion, our results demonstrate that
      SS-31 confers a protective effect in the mouse model of hind limb ischemia
      reperfusion injury preventatively and therapeutically.

PMID- 29589188
TI  - Spatial Visualization ability improves with and without studying Technical
      Drawing.
AB  - The results of several studies suggest that spatial ability can be improved
      through direct training with tasks similar to those integrated in the tests used
      to measure the ability. However, there is a greater interest in analyzing the
      effectiveness of indirect training such as games or of learning subjects that
      involve spatial processes to a certain extent. Thus, the objective of the present
      study was to analyze whether the indirect training in Technical Drawing improved
      the Spatial Visualization ability of Architecture students. For this purpose, a
      group of students enrolled in Fundamentals of Architecture were administered two
      tests, a Spatial Visualization task and an Abstract Reasoning task, at the
      beginning and the end of a semester, after having received training through the
      subjects "Technical Drawing I: Geometry and Perception" and "Projects I." The
      results of this group were compared with those of a control group of students
      enrolled in a Mathematics degree, who were also pre-post evaluated but had not
      received the training in Technical Drawing. The study showed a significant pre
      post improvement in both, Visualization and reasoning. However, this improvement
      occurred in both groups, thereby concluding that this improvement was not due to
      indirect training. Furthermore, no significant differences were found between men
      and women in any of the groups or conditions. These results clarify those of an
      earlier study where improvement in Visualization after training in Technical
      Drawing was found but did not include a comparison with a control condition. The
      control condition has proved to be important in order to consider the limitations
      of the effect of Technical Drawing on said improvement.

PMID- 29589187
TI  - Erythrocyte compression index is impaired in patients with residual vein
      obstruction.
AB  - Defective clot contraction has been postulated to contribute to thrombosis. We
      aimed to evaluate the association of residual vein obstruction (RVO) with
      erythrocyte compression within the whole-blood clot. We studied 32 patients with
      venous thromboembolism (VTE) taking vitamin K antagonists (VKAs) for at least 3
      months (median time in therapeutic range 60%), including 12 (37.5%) with RVO, and
      32 age- and sex-matched controls. In all study participants we evaluated whole
      blood clot retraction, expressed as the erythrocyte compression index (ECI),
      defined as a ratio of mean polyhedrocyte area to mean native erythrocyte area,
      along with clot area covered by polyhedrocytes, plasma clot permeability (Ks),
      clot lysis time (CLT), and thrombin generation. In both groups higher ECI,
      indicating impaired clot contraction, increased with older age, higher body mass
      index, red blood cell distribution width, and lower platelet count (all p <
      0.05), but not with red blood cell count. In VTE patients ECI was 15.8% higher
      than in controls (median 63.6 vs. 54.9%, p = 0.021). Subjects with RVO had 20%
      higher ECI and 155% lower clot area covered by polyhedrocytes. RVO patients had
      also prolonged CLT by 41%, but not Ks, and elevated peak thrombin generation by
      33%, as compared to those without RVO (all p < 0.05). This study is the first to
      show impaired compression of erythrocytes in RVO patients despite VKA
      anticoagulation. Altered ECI coexisted with hypolysability and increased thrombin
      generation. ECI might be useful in the diagnostic process of RVO or post
      thrombotic syndrome and can help optimize the anticoagulant therapy.

PMID- 29589189
TI  - Older adults show less interference from task-irrelevant social categories:
      evidence from the garner paradigm.
AB  - Though age-related difference in most cognitive performance has been found, there
      was no previous research examining age difference in multiple social
      categorizations. Using faces as stimuli and Garner Selective Attention Paradigm,
      this study explored the different characteristics of implicit and explicit social
      categorization between young and older adults. The results showed that young
      perceivers explicitly categorized gender and age of the faces faster and more
      readily than older perceivers did. When young adults judged specific category
      (gender category in Experiment 1; age category in Experiment 2), they were
      interfered from the completing irrelative category; however, irrelative category
      could not capture older adults' attention. These results first suggest
      perceivers' age indeed plays an important role in multiple social
      categorizations.

PMID- 29589190
TI  - Depression During Pregnancy and Its Association with Birth Outcomes: Authors'
      Reply.

PMID- 29589191
TI  - Possibility of modifying the growth trajectory in Raeini Cashmere goat.
AB  - The objective of this study was to investigate the possibility of modifying the
      growth trajectory in Raeini Cashmere goat breed. In total, 13,193 records on live
      body weight collected from 4788 Raeini Cashmere goats were used. According to
      Akanke's information criterion (AIC), the sing-trait random regression model
      included fourth-order Legendre polynomial for direct and maternal genetic effect;
      maternal and individual permanent environmental effect was the best model for
      estimating (co)variance components. The matrices of eigenvectors for
      (co)variances between random regression coefficients of direct additive genetic
      were used to calculate eigenfunctions, and different eigenvector indices were
      also constructed. The obtained results showed that the first eigenvalue explained
      79.90% of total genetic variance. Therefore, changing the body weights applying
      the first eigenfunction will be obtained rapidly. Selection based on the first
      eigenvector will cause favorable positive genetic gains for all body weight
      considered from birth to 12 months of age. For modifying the growth trajectory in
      Raeini Cashmere goat, the selection should be based on the second eigenfunction.
      The second eigenvalue accounted for 14.41% of total genetic variance for body
      weights that is low in comparison with genetic variance explained by the first
      eigenvalue. The complex patterns of genetic change in growth trajectory observed
      under the third and fourth eigenfunction and low amount of genetic variance
      explained by the third and fourth eigenvalues.

PMID- 29589192
TI  - Utilization of Mucuna pruriens whole pods to feed lactating hair ewes.
AB  - Twenty nine Pelibuey * Katahdin hair ewes rearing single lamb were used during 42
      days of lactation to evaluate the effect of including the Mucuna pruriens whole
      pods in the diets of lactating ewes on milk production and offspring performance.
      Animals were distributed at random into three experimental diets: a control diet
      without Mucuna (M0), and two more diets with the inclusion of 13 (M13) and 26%
      (M26), of milled pods of Mucuna pruriens, respectively. Dry matter intake, was
      not significantly different (P > 0.05) among diets. Milk yield (P > 0.05) was
      734, 786, and 694 g/day for diets M0, M13, and M26, respectively. Milk fat (P >
      0.05), milk protein (P > 0.05), and milk lactose (P > 0.05) did not differ
      between treatments. Lambs had similar daily weight gain (P > 0.05) among diets
      (180, 174, and 171 g/day for diets M0, M13, and M26, respectively). Diets with
      Mucuna whole pods were 5.6 and 12.9% more profitable (M13 and M26, respectively)
      than control diet. Under the conditions of this work, Mucuna pruriens whole pods
      can be included up to 26% in the diets of lactating crossbred hair ewes without
      negatively affecting their productive performance during the first 6 weeks of
      lactation.

PMID- 29589193
TI  - Spiral phyllotaxis underlies constrained variation in Anemone (Ranunculaceae)
      tepal arrangement.
AB  - Stabilization and variation of floral structures are indispensable for plant
      reproduction and evolution; however, the developmental mechanism regulating their
      structural robustness is largely unknown. To investigate this mechanism, we
      examined positional arrangement (aestivation) of excessively produced perianth
      organs (tepals) of six- and seven-tepaled (lobed) flowers in six Anemone species
      (Ranunculaceae). We found that the tepal arrangement that occurred in nature
      varied intraspecifically between spiral and whorled arrangements. Moreover, among
      the studied species, variation was commonly limited to three types, including
      whorls, despite five geometrically possible arrangements in six-tepaled flowers
      and two types among six possibilities in seven-tepaled flowers. A spiral
      arrangement, on the other hand, was unique to five-tepaled flowers. A spiral
      phyllotaxis model with stochasticity on initiating excessive primordia accounted
      for these limited variations in arrangement in cases when the divergence angle
      between preexisting primordia was less than 144 degrees . Moreover, interspecific
      differences in the frequency of the observed arrangements were explained by the
      change of model parameters that represent meristematic growth and differential
      organ growth. These findings suggest that the phyllotaxis parameters are
      responsible for not only intraspecific stability but interspecific difference of
      floral structure. Decreasing arrangements from six-tepaled to seven-tepaled
      Anemone flowers demonstrate that the stabilization occurs as development proceeds
      to increase the component (organ) number, in contrast from the intuition that the
      variation will be larger due to increasing number of possible states
      (arrangements).

PMID- 29589194
TI  - Understanding the role of floral development in the evolution of angiosperm
      flowers: clarifications from a historical and physico-dynamic perspective.
AB  - Flower morphology results from the interaction of an established genetic program,
      the influence of external forces induced by pollination systems, and physical
      forces acting before, during and after initiation. Floral ontogeny, as the
      process of development from a meristem to a fully developed flower, can be
      approached either from a historical perspective, as a "recapitulation of the
      phylogeny" mainly explained as a process of genetic mutations through time, or
      from a physico-dynamic perspective, where time, spatial pressures, and growth
      processes are determining factors in creating the floral morphospace. The first
      (historical) perspective clarifies how flower morphology is the result of
      development over time, where evolutionary changes are only possible using
      building blocks that are available at a certain stage in the developmental
      history. Flowers are regulated by genetically determined constraints and
      development clarifies specific transitions between different floral morphs. These
      constraints are the result of inherent mutations or are induced by the
      interaction of flowers with pollinators. The second (physico-dynamic) perspective
      explains how changes in the physical environment of apical meristems create
      shifts in ontogeny and this is reflected in the morphospace of flowers. Changes
      in morphology are mainly induced by shifts in space, caused by the time of
      initiation (heterochrony), pressure of organs, and alterations of the size of the
      floral meristem, and these operate independently or in parallel with genetic
      factors. A number of examples demonstrate this interaction and its importance in
      the establishment of different floral forms. Both perspectives are complementary
      and should be considered in the understanding of factors regulating floral
      development. It is suggested that floral evolution is the result of alternating
      bursts of physical constraints and genetic stabilization processes following each
      other in succession. Future research needs to combine these different
      perspectives in understanding the evolution of floral systems and their
      diversification.

PMID- 29589196
TI  - Debate: the per rectal/digital rectal examination exam in the emergency
      department, still best practice?
AB  - BACKGROUND: Emergency medicine practice in the UK and Ireland offers a junior and
      middle grade doctor great learning opportunities that force engagement with
      multiple specialties, life-saving procedures, exposure to a myriad of patient
      presentations, and opportunities for best practices in medicine. MAIN BODY: The
      emergency department (ED) can be a hectic and dynamic environment; communication
      from the ED to specialists is essential to ensure best clinical outcomes for
      patients. The "per rectal" (PR) or "digital rectal exam" (DRE) can be a very
      difficult diagnostic test for even the most skilled operator to discern
      pathological versus normal; we propose this is especially the case in the
      emergency department patient population. Some specialists require this exam
      performed by an unskilled junior doctor with varying results prior to reviewing a
      referred and sick patient. The PR/DRE benefits may be limited in the ED setting
      for some pathologies, and the result of the exam may have limited impact in the
      overall treatment plan in the ED. CONCLUSION: This short paper reviews the
      indications, benefits, shortfalls, and limitations of the PR/DRE in the emergency
      department setting and offers novel alternatives to maximize best practice,
      ensure best clinical outcomes for patients, and, to first, do no harm.

PMID- 29589195
TI  - Regulation of asymmetric polar auxin transport by PsPIN1 in endodermal tissues of
      etiolated Pisum sativum epicotyls: focus on immunohistochemical analyses.
AB  - This manuscript reports the production of specific polyclonal antibodies for
      PsPIN1, a putative auxin efflux carrier in Alaska pea (Pisum sativum L.) plants,
      and the cellular immunolocalization of PsPIN1. When pea seeds were set with the
      seed axis horizontal to the upper surface of a rockwool block, and allowed to
      germinate and grow for 3 days in the dark, the epicotyl grew upward. On the other
      hand, the application of 2,3,5-triiodobenzoic acid (TIBA) inhibited
      graviresponse. In the subapical epicotyl regions, PsPIN1 has been found to
      localize in the basal side of the plasma membrane of cells in endodermal tissues.
      Asymmetric PsPIN1 localization between the proximal and distal sides of the
      epicotyl was observed, the total amounts of PsPIN1 being more abundant in the
      proximal side. The asymmetric PsPIN1 distribution between the proximal and distal
      sides of the epicotyl was well correlated with unequal polar auxin transport as
      well as asymmetric accumulation of mRNA of PsPIN1 (Ueda et al. in Biol Sci Space
      26:32-41, 2012; Ueda et al. in Plant Biol 16(suppl 1):43-49, 2014). In the
      proximal side of an apical hook, PsPIN1 localized in the basal side of the plasma
      membrane of cells in endodermal tissues, whereas in the distal side, the abundant
      distribution of PsPIN1 localized in the basal-lower (endodermal) side of the
      basal plasma membrane, suggesting possible lateral auxin movement from the distal
      side to the proximal side in this region. The application of TIBA significantly
      reduced the amount of PsPIN1 in the proximal side of epicotyls, but little in the
      distal side. These results suggest that unequal auxin transport in epicotyls
      during the early growth stage of etiolated pea seedlings is derived from
      asymmetric PsPIN1 localization in the apical hook and subapical region of
      epicotyls, and that asymmetric transport between the proximal and distal sides of
      epicotyls is required for the graviresponse of epicotyls.

PMID- 29589197
TI  - Spontaneous bacteremia and spontaneous bacterial peritonitis in cirrhosis: two
      infections but similar outcomes?

PMID- 29589199
TI  - Ditch network maintenance in peat-dominated boreal forests: Review and analysis
      of water quality management options.
AB  - The objective of this study was to evaluate the potential of different water
      management options to mitigate sediment and nutrient exports from ditch network
      maintenance (DNM) areas in boreal peatland forests. Available literature was
      reviewed, past data reanalyzed, effects of drainage intensity modeled, and major
      research gaps identified. The results indicate that excess downstream loads may
      be difficult to prevent. Water protection structures constructed to capture
      eroded matter are either inefficient (sedimentation ponds) or difficult to apply
      (wetland buffers). It may be more efficient to decrease erosion, either by
      limiting peak water velocity (dam structures) or by adjusting ditch depth and
      spacing to enable satisfactory drainage without exposing the mineral soil below
      peat. Future research should be directed towards the effects of ditch breaks and
      adjusted ditch depth and spacing in managing water quality in DNM areas.

PMID- 29589198
TI  - Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y)
      homozygous genotype.
AB  - Although guidelines are available for hereditary hemochromatosis, a high
      percentage of the recommendations within them are not shared between the
      different guidelines. Our main aim is to provide an objective, simple, brief, and
      practical set of recommendations about therapeutic aspects of HFE hemochromatosis
      for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published
      scientific studies and guidelines, in a form that is reasonably comprehensible to
      patients and people without medical training. This final version was approved at
      the Hemochromatosis International meeting on 12th May 2017 in Los Angeles.

PMID- 29589200
TI  - Molecular recognition of flunarizine dihydrochloride and beta-cyclodextrin
      inclusion complex by NMR and computational approaches.
AB  - BACKGROUND: Flunarizine dihydrochloride (FLN) is used in the prophylactic
      treatment of migraine, vertigo, occlusive peripheral vascular disease and
      epilepsy. Cyclodextrins (CDs) are chiral, truncated cone shaped macrocycles known
      for their inner hydrophobic and outer hydrophilic site. They form complexes with
      hydrophobic drug molecules and enhance the solubility and bioavailability of such
      compounds by enhancing drug permeability through mucosal tissues. NMR
      spectroscopy and computational docking have been recognized as an important tool
      for the interaction study of CDs-drug inclusion complexes in solution state.
      RESULTS: The structural assignments of FLN and beta-CD protons were determined by
      1H NMR and 2D 1H-1H COSY NMR spectroscopy. 1H NMR spectroscopic studies of FLN,
      beta-CD and their mixtures confirmed the formation of beta-CD-FLN inclusion
      complex in solution. 1H NMR titration data for beta-CD-FLN inclusion complex
      showed 1:1 stoichiometry, an association constant of K a  = 157 M-1 and change in
      Gibbs free energy of ?G = - 12.65 kJ mol-1. The binding constant of the beta-CD
      inclusion complex with two nearly similar structures, FLN and cetirizine
      dihydrochloride, were compared. Two-dimensional 1H-1H ROESY spectral data and
      molecular docking studies showed the modes of penetration of the aromatic rings
      from the wider rim side into the beta-CD cavity. The possible geometrical
      structures of the beta-CD-FLN inclusion complex have been proposed in which
      aromatic rings protrude close to the narrower rim of the beta-CD truncated cone.
      CONCLUSION: NMR spectroscopic studies of FLN, beta-CD and FLN:beta-CD mixtures
      confirmed the formation of 1:1 inclusion complex in solution at room temperature.
      Two-dimensional 1H-1H ROESY together with molecular docking study confirmed that
      the F-substituted aromatic ring of FLN penetrates into beta-CD truncated cone and
      the tail of aromatic rings were proximal to narrower rim of beta-CD. The
      splitting of aromatic signals of FLN in the presence of beta-CD suggests chiral
      differentiation of the guest FLN by beta-CD.

PMID- 29589201
TI  - The Potential Role of Toll-Like Receptor 4 in Mediating Dopaminergic Cell Loss
      and Alpha-Synuclein Expression in the Acute MPTP Mouse Model of Parkinson's
      Disease.
AB  - Toll-like receptors (TLRs) may have a role in Parkinson's disease (PD). In this
      study, we aimed at investigating the dopaminergic cell loss and alpha-synuclein
      (alpha-SYN) expression in TLR4-deficient mice (TLR4-/-) acutely exposed to 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a pharmacological PD model.
      TLR4 ablation restrained the number of dopaminergic neurons in the substantia
      nigra (SN), as assessed by tyrosine hydroxylase (TH) protein expression.
      Intriguingly, TLR4-/- mice showed massive alpha-SYN protein accumulation in the
      midbrain along with high alpha-SYN mRNA levels in cerebral cortex, striatum,
      hippocampus, and cerebellum. Contrary to expectations, the high levels of alpha
      SYN do not correlate with greater dopaminergic neuronal loss. The levels of
      nigral alpha-SYN protein in TLR4-/- mice further, but not significantly,
      increased during MPTP treatment. Contrariwise, MPTP treatment significantly
      induced the mRNA expression of alpha-SYN in examined brain regions of WT and TLR4
      /- mice. Protein levels of GATA2, a transcription factor proposed to control
      alpha-SYN gene expression, did not change in TLR4-/- mice at baseline and after
      MPTP treatment. These findings suggest a role for TLR4 in mediating dopaminergic
      cell loss and in the constitutive expression of brain alpha-SYN. However, further
      exploration is needed in order to establish the actual role of alpha-SYN in the
      relative absence of TLR4.

PMID- 29589202
TI  - The Impact of Five VDR Polymorphisms on Multiple Sclerosis Risk and Progression:
      a Case-Control and Genotype-Phenotype Study.
AB  - Vitamin D receptor polymorphisms have been the target of many studies focusing on
      multiple sclerosis. However, previously reported results have been inconclusive.
      The objective of this study was to investigate the association between five
      vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple
      sclerosis susceptibility and its course. The study was carried out as a case
      control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis
      patients and 135 healthy controls. Genotyping was carried out using polymerase
      chain reaction and restriction analysis. In multiple sclerosis men, allele and/or
      genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as
      compared to controls (EcoRV, pa = 0.02; Taq, pg = 0.02, pa = 0.02; BsmI, pg =
      0.02, pa = 0.04; ApaI, pg = 0.008, pa = 0.005). In multiple sclerosis women,
      differences in the frequency of alleles and genotypes were found to be
      significant in ApaI (controls vs multiple sclerosis women: pg = 0.01, pa = 0.05).
      Conclusive results were observed between multiple sclerosis women in the case of
      EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype
      was found to increase the risk of primary progressive multiple sclerosis 5.5
      times (CT vs CC+TT pcorr = 0.01, sensitivity 0.833, specificity 0.525, power test
      0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p =
      0.05)]. Our results indicate that the distribution of investigated vitamin D
      receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and
      progression in the Czech population. The association between disease risk and
      polymorphisms was found to be stronger in men. The association of disease
      progression with polymorphisms was observed only in women.

PMID- 29589203
TI  - Anabolic Therapy for the Treatment of Osteoporosis in Childhood.
AB  - PURPOSE OF REVIEW: Numerous forms of osteoporosis in childhood are characterized
      by low bone turnover (for example, osteoporosis due to neuromuscular disorders
      and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to
      treat osteoporosis in the young, is associated with further reductions in bone
      turnover, raising concerns about the long-term safety and efficacy of such
      therapy. These observations have led to increasing interest in the role of
      anabolic therapy to treat pediatric osteoporosis. RECENT FINDINGS: While growth
      hormone and androgens appears to be relatively weak anabolic modulators of bone
      mass, emerging therapies targeting bone formation pathways (anti-transforming
      growth factor beta antibody and anti-sclerostin antibody) hold considerable
      promise. Teriparatide remains an attractive option that merits formal study for
      patients post-epiphyseal fusion, although it must be considered that adult
      studies have shown its effect is blunted when administered following
      bisphosphonate therapy. Mechanical stimulation of bone through whole body
      vibration therapy appears to be much less effective than bisphosphonate therapy
      for treating osteoporosis in children. New anabolic therapies which target
      important pathways in skeletal metabolism merit further study in children,
      including their effects on fracture risk reduction and after treatment
      discontinuation.

PMID- 29589204
TI  - New literacy challenge for the twenty-first century: genetic knowledge is poor
      even among well educated.
AB  - We live in an age of rapidly advancing genetic research. This research is
      generating new knowledge that has implications for personal health and well
      being. The present study assessed the level of genetic knowledge and personal
      engagement with genetics in a large sample (N = 5404) of participants.
      Participants received secondary education in 78 countries, with the largest
      samples from Russia, the UK and the USA. The results showed significant group
      differences in genetic knowledge between different countries, professions,
      education levels and religious affiliations. Overall, genetic knowledge was poor.
      The questions were designed to assess basic genetic literacy. However, only 1.2%
      of participants answered all 18 questions correctly, and the average score was
      65.5%. Genetic knowledge was related to peoples' attitudes towards genetics. For
      example, those with greater genetic knowledge were on average more willing to use
      genetic knowledge for their personal health management. Based on the results, the
      paper proposes a number of immediate steps that societies can implement to
      empower the public to benefit from ever-advancing genetic knowledge.

PMID- 29589206
TI  - Saline-push improves rubidium-82 PET image quality.
AB  - INTRODUCTION: Rubidium-82 (82Rb) PET is used widely for myocardial perfusion
      imaging. The purpose of this study was to investigate if an additional saline
      push following the 82Rb elution improves PET image quality. METHODS: 82Rb PET
      scans were acquired with and without 26 mL saline-push in six patients as part of
      a clinical quality improvement program. Dynamic images were analyzed to measure
      the total activity delivered to the superior vena cava (SVC) and retained in the
      left ventricle (LV) myocardium. Tracer uptake images were used to measure blood
      background coefficient-of-variation (COV), myocardium-to-blood signal-to-noise
      ratio (SNR), and contrast-to-noise ratio (CNR) to assess image quality. RESULTS:
      Similar eluted activity was measured with/without the saline-push (830 vs 795
      MBq; P = 0.24). The activity delivered to the heart and retained in the
      myocardium was consistently increased more than twofold (SVC: + 114% and LV: +
      104%; P < 0.001) with the saline-push. Image quality was improved in all
      patients, with lower background noise (COV: - 19%), higher SNR (+ 24%) and CNR (+
      27%) (all P <= 0.01). CONCLUSIONS: The saline-push used to flush 82Rb activity
      out of the infuser tubing, patient injection and intravenous access lines
      consistently increased the activity delivered to the heart by twofold. This
      technique is recommended to maximize image quality with 82Rb PET.

PMID- 29589205
TI  - Hyperchloraemia in sepsis.
AB  - Chloride represents-quantitatively-the most prevalent, negatively charged, strong
      plasma electrolyte. Control of chloride concentration is a probable major
      mechanism for regulating the body's acid-base balance and for maintaining
      homeostasis of the entire internal environment. The difference between the
      concentrations of chloride and sodium constitutes the major contributor to the
      strong ion difference (SID); SID is the key pH regulator in the body, according
      to the physicochemical approach. Hyperchloraemia resulting from either underlying
      diseases or medical interventions is common in intensive care units. Recent
      studies have demonstrated the importance of hyperchloraemia in metabolic acidosis
      and in other pathophysiological disorders present in sepsis. The aim of this
      narrative review is to present the current knowledge about the effects of
      hyperchloraemia, in relation to the underlying pathophysiology, in septic
      patients.

PMID- 29589207
TI  - Do we really need to look at volumetric measurements with 99mTc single photon
      emission computed tomography (SPECT) myocardial perfusion imaging?

PMID- 29589208
TI  - Significance of 11C-PIB PET/CT in cardiac amyloidosis compared with 99mTc
      aprotinin scintigraphy: A pilot study.
AB  - BACKGROUND: This study was to investigate the significance of 11C-Pittsburgh B
      (PIB) PET/CT in patients with suspected cardiac amyloidosis compared with 99mTc
      aprotinin scintigraphy. METHODS: Thirteen consecutive patients with suspected
      cardiac amyloidosis were considered for enrolment in this prospective pilot
      study. Participants were scheduled to undergo a series of 11C-PIB PET/CT and
      99mTc-aprotinin within a 2-month period. Finally, we evaluated nine cases who
      underwent both imaging modalities, and compared imaging results with clinical and
      pathological results and prognosis. RESULTS: Six of the 9 patients who underwent
      both imaging modalities were diagnosed with amyloidosis, of whom 3 patients were
      diagnosed with cardiac amyloidosis from endomyocardial biopsy. These 3 patients
      with positive 11C-PIB uptake at the left ventricle wall showed worsening of
      cardiac function progressing in the short term or death caused by acute
      exacerbation of chronic heart failure. Six of 8 patients with positive uptake on
      99mTc-aprotinin presented with amyloid deposition in the left ventricle wall, but
      symptoms remained stable if results of 11C-PIB were not positive. CONCLUSION: In
      a small sample of subjects, the present study showed that 11C-PIB accumulation in
      myocardium indicated cardiac amyloidosis with poor prognosis. Uptake of 11C-PIB
      may be related to progressive amyloid deposition to the heart and can predict
      patient prognosis.

PMID- 29589209
TI  - Nucleated red blood cells as predictors of mortality in patients with acute
      respiratory distress syndrome (ARDS): an observational study.
AB  - BACKGROUND: Nucleated red blood cells (NRBCs) in critically ill patients are
      associated with increased mortality and poor outcome. The aim of the present
      study was to evaluate the predictive value of NRBCs in patients with acute
      respiratory distress syndrome (ARDS). METHODS: This observational study was
      conducted at an ARDS referral center and included patients from 2007 to 2014.
      Daily NRBC counts were assessed and the predictive validity of NRBCs on mortality
      was statistically evaluated. A cutoff for prediction of mortality based on NRBCs
      was evaluated using ROC analysis and specified according to Youden's method.
      Multivariate nonparametric analysis for longitudinal data was applied to prove
      for differences between groups over the whole time course. Independent predictors
      of mortality were identified with multiple logistic and Cox' regression analyses.
      Kaplan-Meier estimations visualized the survival; the corresponding curves were
      tested for differences with the log-rank test. RESULTS: A total of 404 critically
      ill ARDS patients were analyzed. NRBCs were found in 75.5% of the patients, which
      was associated with longer length of ICU stay [22 (11; 39) vs. 14 (7; 26) days; p
      < 0.05] and higher mortality rates (50.8 vs. 27.3%; p < 0.001). Logistic
      regression analysis with mortality as response showed NRBC positivity per se to
      be an independent risk factor for mortality in ARDS with a doubled risk for ICU
      death (OR 2.03; 95% CI 1.16-3.55; p < 0.05). Also, NRBC value at ICU admission
      was found to be an independent risk factor for mortality (OR 3.25; 95% CI 1.09
      9.73, p = 0.035). A cutoff level of 220 NRBC/ul was associated with a more than
      tripled risk of ICU death (OR 3.2; 95% CI 1.93-5.35; p < 0.0001). ARDS patients
      below this threshold level had a significant survival advantage (median survival
      85 days vs. 29 days; log rank p < 0.001). Presence of a severe ARDS was
      identified as independent risk factor for the occurrence of NRBCs > 220/ul (OR
      1.81; 95% CI 1.1-2.97; p < 0.05). CONCLUSIONS: NRBCs may predict mortality in
      ARDS with high prognostic power. The presence of NRBCs in the blood might be
      regarded as a marker of disease severity indicating a higher risk of ICU death.

PMID- 29589210
TI  - The effect of flow on viscoelastic emulsion microstructure.
AB  - Emulsions made of oil, water and surfactants are widespread soft materials with
      complex structures depending on composition and temperature. Emulsion phase
      behavior at rest has been widely investigated but flow-induced effects, which are
      very relevant in many applications, can still be further explored towards
      improved emulsion microstructural design. In this work, we use low energy
      emulsification processing to create small-sized emulsions. In a previous report,
      we showed the emulsion morphology development and the effect of flow on the
      microstructure of a highly viscoelastic attractive emulsion which result in a
      concentrated nanoemulsion after viscoelastic droplet filaments are disrupted.
      Here, we show that upon stopping the flow, the filaments slowly buckle, recoil
      and finally form clusters of randomly flocculated droplets. We thus obtain two
      completely different emulsion morphologies simply induced by the action of flow,
      where in both cases attractive interactions play a key role. The emulsion high
      interfacial area represents a valuable feature for several applications such as
      upstream operations, microreaction media and drug delivery.

PMID- 29589211
TI  - A modified multi-patch technique for double-layered repair of ischemic posterior
      ventricular septal rupture.
AB  - BACKGROUND: The rupture of the posterior ventricular septum after acute inferior
      myocardial infarction is more challenging to repair than ruptures in other sites
      since it is less accessible and anatomically restricted. We described a
      modification of Daggett's original technique of multi-patch repair of ruptured
      posterior septum. CASE PRESENTATION: The technique was employed in the operation
      of a 67-year-old male who presented with severe heart failure at the 10th day
      after he developed inferior myocardial infarction. His ventricular septum had
      ruptured at the level between the posteromedial papillary muscle and the mitral
      annulus. A large endoventricular patch covered separately over the locally
      patched septal defect and the ventriculotomy defect which was going to be roofed
      eventually with an external patch. Both defects were then individually closed in
      double layers, holding a single continuous patch in common. The common use of a
      single patch expedited multilayered closure of the left ventricular defects and
      could minimize geometric remodeling of the covered area. The patches on both the
      endocardial and the epicardial sides avoided potentially fatal bleeding from the
      ventriculotomy site. The transmural mattress sutures incorporating ventriculotomy
      patches required minimal bites toward the posteromedial papillary muscle and
      mitral annulus, thereby preserving the mitral valve function. CONCLUSIONS: Thus,
      the technique enhances the advantage of the left ventriculotomy in the repair of
      posterior septal rupture and avoids ventriculotomy-related morbidity.

PMID- 29589212
TI  - Psychometric properties of the Satisfaction with Life Scale (SWLS), derived from
      a large German community sample.
AB  - PURPOSE: The aim of this study was to test psychometric properties of the
      Satisfaction with Life Scale (SWLS), to provide normative values, and to analyze
      associations between life satisfaction and sociodemographic and behavioral data.
      METHODS: A German community sample (n = 9711) with an age range of 18-80 years
      was surveyed using the SWLS and several other questionnaires. Confirmatory factor
      analysis (CFA) was used to test the dimensionality of the SWLS. Invariance across
      gender and age groups was tested with multiple-group CFA. Associations between
      SWLS, sociodemographic variables, and behavioral variables were tested with
      ANOVAs. RESULTS: Confirmatory factorial analysis results confirmed that the SWLS
      is a one-dimensional scale. Measurement invariance across gender was completely
      confirmed, while concerning age strict measurement invariance was confirmed. The
      effects of gender and age on satisfaction with life were weak. Satisfaction with
      life was associated with fatigue (r = - .49), the mental component of quality of
      life (r = .45), anxiety (r = - .42), dispositional optimism (r = .41), pessimism
      (r = - .34), sleep quality (r = - .32), and sociodemographic factors such as
      marital status, income, and occupational status. Non-smokers reported higher life
      satisfaction than smokers. CONCLUSIONS: Because of the good psychometric
      properties, the SWLS can be recommended for use in epidemiological research.
      Normative values based on a large community sample are provided.

PMID- 29589213
TI  - Effects of Some Growth Factors and Cytokines on the Expression of the Repair
      Enzyme MGMT and Protein MARP in Human Cells In Vitro : Effect of Some Growth
      Factors and Cytokines.
AB  - The inducible repair enzyme O6-methylguanine-DNA methyltransferase (MGMT)
      eliminates O6-methylguanine adducts in DNA and protects the cells from damaging
      effects of alkylating agents. We have found that anti-MGMT antibodies recognize
      both the MGMT protein with a mol. weight ~ 24 kDa and a protein with a mol.
      weight ~ 48 kDa, which was named MARP (anti-methyltransferase antibody
      recognizable protein). A number of growth factors and cytokines were shown to
      regulate the expression of MGMT and MARP proteins. The ranges of concentrations
      of several growth factors and cytokines that caused increasing or decreasing
      protein amounts in human cell cultures were determined. The results of special
      biological experiments have allowed us to assume a possible role of MARP in the
      repair of alkyl adducts in human cells.

PMID- 29589214
TI  - Association of Tumor Necrosis Factor Alpha-Induced Protein 3 Interacting Protein
      1 (TNIP1) Gene Polymorphism (rs7708392) with Lupus Nephritis in Egyptian
      Patients.
AB  - Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic
      lupus erythematosus (SLE). Previous studies suggest that mutant A20 binding
      inhibitor of NF-kappaB 1 (ABIN1) protein encoded by tumor necrosis factor alpha
      induced protein 3 interacting protein 1 (TNIP1) gene is associated with LN via NF
      kappaB dysregulation. The aim of the current study was to evaluate the
      association of TNIP1 gene SNP rs7708392 with SLE and LN in Egyptian patients. 5'
      nuclease Allelic discrimination was used to evaluate the frequency of TNIP1 SNP
      rs7708392 in 53 patients with LN, 57 SLE patients without nephritis and 85
      healthy controls. The genotyping analysis revealed that the CC genotype was more
      frequent in controls than SLE patients, while GC and GG genotypes were more
      common in SLE patients. Moreover, the GG genotype and the G allele were
      significantly more prevalent among LN patient than non-LN patients (P < 0.001).
      In LN patients, the most common genotype was GG (56.6%), while among the non-LN
      patients; the CG genotype was the most common (59.6%). Regression analysis
      demonstrated that SLE patients carrying only one G allele had a 3.4 folds
      increased risk for LN. Our results suggested that TNIP1 SNP (rs7708392) might be
      associated with the LN in Egyptian SLE patients. TNIP1 SNP (rs7708392) might be
      used to identify patients at risk of developing LN, which could help in early
      detection and treatment before progression to end-stage renal disease, improving
      patients' outcome and quality of life.

PMID- 29589215
TI  - Cellular Glucose Uptake During Breath-Hold Diving in Experienced Male Breath-Hold
      Divers.
AB  - BACKGROUND: The physiological and pathophysiological mechanisms that govern
      diving, both self-contained underwater breathing apparatus (SCUBA) and breath
      hold diving (BH-diving), are in large part well known, even if there are still
      many unknown aspects, in particular about cell metabolism during BH-diving. The
      scope of this study was to investigate changes in glycemia, insulinemia, and the
      catecholamine response to BH-diving, to better understand if the insulin
      stimulated glucose uptake mechanism is involved in cellular metabolism in this
      sport. METHODS: Twenty male experienced healthy breath-hold divers were studied.
      Anthropometric information was obtained. Glycemia, insulinemia, and catecholamine
      response were investigated before and after the series of BH-diving. RESULTS: We
      found a statistically significant decrease in the blood glucose levels between
      before and after dives (mean 94.3 +/- 11.6 vs. 83.5 +/- 12.5 mg/dl) P = 0.001 and
      a statistically significant increase in blood insulin value (median 4.5 range
      3.4/6.4 vs. 7.0 range 4.2/10.2 mcgU/ml) P < 0.0001. Also, we found a
      statistically significant increase of catecholamine production (median 14.0 range
      8/18 vs. 15.5 range 10.0/21.0 MUg) P < 0.0001. CONCLUSIONS: The increase in blood
      insulin during BH-diving associated with the decrease of blood glucose levels
      could indicate that the upregulating cellular uptake is not caused by activation
      of the specific glucose transporters. Particular diving-related conditions such
      as the diving reflex, the intermittent hypoxia/hyperoxia, and the particular
      environmental condition could play an important role in the mechanism involved in
      glycemia decrease in BH-diving. Our data confirm that the adaptations to BH
      diving are caused by complex mechanisms and involve many peculiar responses still
      in large part unknown.

PMID- 29589216
TI  - Vernier But Not Grating Acuity Contributes to an Early Stage of Visual Word
      Processing.
AB  - The process of reading words depends heavily on efficient visual skills,
      including analyzing and decomposing basic visual features. Surprisingly, previous
      reading-related studies have almost exclusively focused on gross aspects of
      visual skills, while only very few have investigated the role of finer skills.
      The present study filled this gap and examined the relations of two finer visual
      skills measured by grating acuity (the ability to resolve periodic luminance
      variations across space) and Vernier acuity (the ability to detect/discriminate
      relative locations of features) to Chinese character-processing as measured by
      character form-matching and lexical decision tasks in skilled adult readers. The
      results showed that Vernier acuity was significantly correlated with performance
      in character form-matching but not visual symbol form-matching, while no
      correlation was found between grating acuity and character processing.
      Interestingly, we found no correlation of the two visual skills with lexical
      decision performance. These findings provide for the first time empirical
      evidence that the finer visual skills, particularly as reflected in Vernier
      acuity, may directly contribute to an early stage of hierarchical word
      processing.

PMID- 29589217
TI  - Identification and characterization of inorganic-phosphate-solubilizing bacteria
      from agricultural fields with a rapid isolation method.
AB  - The ability to solubilize fixed inorganic phosphorus (P) for plant growth is
      important for increasing crop yield. More P can be released by inoculating soil
      with inorganic-phosphate-solubilizing bacteria (iPSBs). We used 96-well
      microplates instead of traditional 200-mm petri dishes to rapidly screen iPSB
      strains for their solubilizing ability. We simultaneously obtained 76 iPSB
      isolates from 576 wells containing two agricultural soils. This method
      conveniently identified positive iPSB strains and effectively prevented fungal
      cross-contamination. Maximum-likelihood phylogenetic trees of the isolated
      strains showed that Bacillus megaterium was the most dominant iPSB, and strains
      Y99, Y95, Y924 and Y1412 were selected as representatives for the analysis of P
      solubilization. Succinic acid was the main organic acid of B. megaterium for
      releasing P. It was strongly correlated with the increase in soluble P
      concentration during 168 h of incubation of these four strains. pH was negatively
      exponentially correlated with the amount of soluble P in the medium, and the
      amount of succinic acid was strongly linearly correlated with the amount of P
      released (P < 0.001), suggesting that organic acid may mobilize microbial P. Our
      study provides an efficient and effective method for identifying and analyzing
      the growth of iPSB strains able to solubilize inorganic P and gives a better
      understanding of the mechanism of P solubilization.

PMID- 29589218
TI  - Mental Health Attitudes and Beliefs in a Community Sample on the Central Coast in
      Australia: Barriers to Help Seeking.
AB  - There continues to be call for greater community awareness actions and strategies
      to reduce stigma and enhance mental health literacy nationally and
      internationally. To identify local barriers to help-seeking and perceptions
      around stigma, we developed a 'mental health attitudes and beliefs' survey which
      was administered at a range of community events on the Central Coast in New South
      Wales, Australia. The aim was for the results of this survey to inform the
      development of strategies that enhance local help-seeking behaviours that are
      sensitive to the role of age, gender and Indigenous status. People who approached
      our Mental Health Information stall were invited to complete the survey and 282
      individuals completed the survey. The data was analysed descriptively with a
      focus on comparing subgroups based on age, gender, Indigenous status, and
      previous service access or experience of mental illness. Cost, stigma and mental
      health literacy were found to be prominent barriers to help-seeking for the
      overall cohort; however, the ways in which or extent to which these barriers
      impact on help seeking varied between subgroups. A discussion of these
      differences and their implications for practice is the focus of this paper.

PMID- 29589219
TI  - Risk Factors for Suicide in Older Inpatient Veterans with Schizophrenia.
AB  - Patients with schizophrenia have an elevated risk of suicidal behavior. We
      explored whether there were age differences in inpatients with schizophrenia
      admitted for suicidal behavior. We compared demographic/clinical characteristics
      of 76 inpatients aged > 59 to those < 60. All patients had a score greater > 0 on
      items 4 (active suicidality) and/or 5 (passive suicidality) on the Beck Scale for
      Suicidal Ideation for inclusion. There were no significant group differences with
      respect to race, education, depressive symptoms or negative symptoms. There was
      evidence suggesting that hallucinations appear to be less prominent in the older
      group. Future studies will determine whether these age related differences are
      stable over time and could account for potential age differences in suicidal
      behavior in individuals with schizophrenia.

PMID- 29589220
TI  - Ocular involvement in melioidosis: a 23-year retrospective review.
AB  - BACKGROUND: Ocular involvement in melioidosis is rare and has devastating
      outcomes. Although there have been few reports on the condition, Khon Kaen, a
      city in northeast Thailand, has been called the "capital of melioidosis" due to
      the high prevalence of the condition in the region. We retrospectively reviewed
      all admitted cases of melioidosis with ocular involvement from the two largest
      hospitals in Khon Kaen. We reviewed cases from Srinagarind Hospital (a university
      hospital) of patients admitted between 1993 and 2016 and from Khon Kaen Hospital
      (a provincial hospital) of patients who presented from 2012 to 2016. RESULTS: We
      identified 16 cases of ocular involvement. Eight of these cases were proven from
      positive culture, and the remaining eight were implied from high melioidosis
      titer. The prevalence was estimated as being from 0.49 to 1.02%. Most patients
      had underlying diseases (14, 88%), of which diabetes mellitus was the most
      prevalent (12, 75%). Nine cases (56%) were part of disseminated septicemia.
      Patients suffered from blindness in 11 (73%) of the 15 cases in which visual
      acuity was recorded. Orbital cellulitis was the most common manifestation (7,
      44%) followed by endophthalmitis (4, 25%). Interestingly, all patients with
      necrotizing fasciitis (100%) developed septic shock as a consequence. In most of
      the cases, patients underwent surgery (13, 81%) including incision and drainage,
      debridement, and pars plana vitrectomy. Despite appropriate management, the
      visual outcomes were disappointing (9, 64%). CONCLUSION: To summarize, ocular
      melioidosis is a highly destructive disease. Early detection and prompt surgical
      management may reduce morbidity and mortality from septic shock.

PMID- 29589221
TI  - Long-term survival with repeat resection for lung oligometastasis from pancreatic
      ductal adenocarcinoma: a case report.
AB  - BACKGROUND: Long-term survival after resection of metastases from pancreatic
      ductal adenocarcinoma is rare. CASE PRESENTATION: A 54-year-old man underwent
      pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with
      UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM).
      Three years after radical resection of the primary tumor, a tiny nodule was found
      in the lower lobe of the left lung. Despite treatment with GEM, it increased
      gradually, but no other metastases were found. Eighteen months after the first
      indication of the nodule, wedge resection was performed. Pathological examination
      of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy
      was again performed for lung oligometastases at 77 and 101 months after PD. The
      patient has been asymptomatic without tumor recurrence for 4 years since the last
      pulmonary resection. CONCLUSIONS: In PDAC, the treatment strategy for
      oligometastasis is controversial. However, a few cases of long-term survival
      after pulmonary metastasectomy for oligometastasis of PDAC have been reported.
      More such cases need to be studied to address this issue effectively.

PMID- 29589222
TI  - Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin
      Pulmonary Delivery: Optimization by Factorial Design.
AB  - A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved
      organic solubility was synthesized, characterized, and employed for the
      preparation of rifampicin (Rif) encapsulated nanoparticle formulations for
      pulmonary delivery. OC was characterized to confirm acyl group substitution and
      cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the
      double emulsion solvent evaporation technique without cross-linking and
      characterized for particle size distribution, morphology, crystallinity, thermal
      stability, aerosol delivery, and drug release rate. OC was successfully
      synthesized with substitution degree of 44.05 +/- 1.75%, and solubility in a
      range of organic solvents. Preliminary cytotoxicity studies of OC showed no
      effect on cell viability over a period of 24 h on A549 cell lines. OC
      nanoparticles were optimized using a 32 full factorial design. An optimized batch
      of OC nanoparticles, smooth and spherical in morphology, had mean hydrodynamic
      diameter of 253 +/- 19.06 nm (PDI 0.323 +/- 0.059) and entrapment efficiency of
      64.86 +/- 7.73% for rifampicin. Pulmonary deposition studies in a two-stage
      impinger following aerosolization of nanoparticles from a jet nebulizer gave a
      fine particle fraction of 43.27 +/- 4.24%. In vitro release studies indicated
      sustained release (73.14 +/- 3.17%) of rifampicin from OC nanoparticles over 72
      h, with particles demonstrating physical stability over 2 months. In summary, the
      results confirmed the suitability of the developed systems for pulmonary delivery
      of drugs with excellent aerosolization properties and sustained-release
      characteristics.

PMID- 29589223
TI  - An Analysis of the Inclusion of Medications Considered Potentially Inappropriate
      in Older Adults in Chemotherapy Templates for Hematologic Malignancies: One
      Recommendation for All?
AB  - BACKGROUND: There remains a paucity of data regarding the use of potentially
      inappropriate medications (PIMs) in the supportive management of older adults
      undergoing chemotherapy. Raising awareness among healthcare providers regarding
      the frequency of their use and potential toxicities may help to minimize the
      risks to patients. OBJECTIVE: The aim of this study was to evaluate the frequency
      of six specific classes of medications considered PIMs by the American Geriatrics
      Society Beers Criteria that are commonly included in the National Comprehensive
      Cancer Network (NCCN) chemotherapy order templates for hematologic malignancies.
      The six PIMs evaluated are first-generation antihistamines, benzodiazepines,
      corticosteroids, H2-receptor antagonists, metoclopramide, and antipsychotics.
      METHODS: A total of 311 unique chemotherapy order templates published online by
      the NCCN for the treatment of hematologic malignancies were reviewed to determine
      the frequency that these six specific PIMs were recommended for supportive care.
      RESULTS: Approximately 45% of the NCCN chemotherapy templates for hematologic
      malignancies specifically recommended the use of at least one of the six PIMs
      examined. The remainder of the templates evaluated referred exclusively to the
      NCCN Guidelines(r) on Oncology for Antiemesis, which also included the use of at
      least one of the six PIMs evaluated. CONCLUSIONS: These findings demonstrate that
      PIMs are frequently used as supportive therapy in the treatment of hematologic
      malignancies. Increasing healthcare provider awareness of their potential side
      effects may minimize the risks associated with their use in older adults with
      hematologic malignancies undergoing chemotherapy.

PMID- 29589224
TI  - Comparison of three-parameter kinetic model analysis to standard Patlak's
      analysis in 18F-FDG PET imaging of lung cancer patients.
AB  - BACKGROUND: Patlak's graphical analysis can provide tracer net influx constant
      (Ki) with limitation of assuming irreversible tracer trapping, that is, release
      rate constant (kb) set to zero. We compared linear Patlak's analysis to non
      linear three-compartment three-parameter kinetic model analysis (3P-KMA)
      providing Ki, kb, and fraction of free 18F-FDG in blood and interstitial volume
      (Vb). METHODS: Dynamic PET data of 21 lung cancer patients were retrospectively
      analyzed, yielding for each patient an 18F-FDG input function (IF) and a tissue
      time-activity curve. The former was fitted with a three-exponentially decreasing
      function, and the latter was fitted with an analytical formula involving the
      fitted IF data (11 data points, ranging 7.5-57.5 min post-injection). Bland
      Altman analysis was used for Ki comparison between Patlak's analysis and 3P-KMA.
      Additionally, a three-compartment five-parameter KMA (5P-KMA) was implemented for
      comparison with Patlak's analysis and 3P-KMA. RESULTS: We found that 3P-KMA Ki
      was significantly greater than Patlak's Ki over the whole patient series, + 6.0%
      on average, with limits of agreement of +/- 17.1% (95% confidence). Excluding 8
      out of 21 patients with kb > 0 deleted this difference. A strong correlation was
      found between Ki ratio (=3P-KMA/Patlak) and kb (R = 0.801; P < 0.001). No
      significant difference in Ki was found between 3P-KMA versus 5P-KMA, and between
      5P-KMA versus Patlak's analysis, with limits of agreement of +/- 23.0 and +/-
      31.7% (95% confidence), respectively. CONCLUSIONS: Comparison between 3P-KMA and
      Patlak's analysis significantly showed that the latter underestimates Ki because
      it arbitrarily set kb to zero: the greater the kb value, the greater the Ki
      underestimation. This underestimation was not revealed when comparing 5P-KMA and
      Patlak's analysis. We suggest that further studies are warranted to investigate
      the 3P-KMA efficiency in various tissues showing greater 18F-FDG trapping
      reversibility than lung cancer lesions.

PMID- 29589225
TI  - Low concordance between surgical and radiological assessment of degree of
      resection and treatment-related hypothalamic damage: results of KRANIOPHARYNGEOM
      2007.
AB  - BACKGROUND: Assessment of presurgical hypothalamic involvement (psHI) and
      treatment-related hypothalamic damage (trHD) is relevant for the decision on risk
      adapted treatment and rehabilitation strategies in craniopharyngioma. PATIENTS
      AND METHODS: 129 surgical reports of childhood-onset craniopharyngioma patients
      recruited 2007-2014 in KRANIOPHARYNGEOM 2007 were analyzed. Data on psHI were
      available based on surgeon's (63%), reference neuroradiologist's (95%), and local
      radiologist's (23%) assessment. The surgical degree of resection (DoR) was
      assessed by neurosurgeon (95%), reference neuroradiologist (73%), and local
      radiologist (61%). TrHD was assessed by neurosurgeon (33%), by reference
      neuroradiologist (95%), and by local radiologist (2%). Neurosurgical center size
      was categorized based on patient load. RESULTS: Surgical assessments on psHI (n =
      78), DoR (n = 89) and trHD (n = 42) as documented in surgical reports could be
      compared with the assessment of respective parameters by reference
      neuroradiologist. Differences with regard to DoR (p = 0.0001) and trHD (p <
      0.0001) were detectable between surgeon's and reference neuroradiologist's
      assessment, whereas psHI was assessed similarly. Concordance for DoR and trHD was
      observed in 48 and 62%, respectively. Surgeons estimated a higher rate of
      complete resections and a lower rate of trHD. Neuroradiological reference
      assessment of trHD had higher predictive value for hypothalamic sequelae then
      surgical assessment. Observed differences were not related to neurosurgical
      center size. CONCLUSIONS: Observed differences between surgical and
      neuroradiological estimation of risk factors in craniopharyngioma support the
      necessity of neuroradiological reference review to assure standards of quality.
      This could be established by central internet-based neuroradiological review in
      KRANIOPHARYNGEOM 2007. Standardization of surgical reports including specific
      assessment of tumor/damage location is recommended.

PMID- 29589227
TI  - Morphological reflections of evolutionary adaptations in the tongue of the white
      headed duck.
AB  - During an organism's evolution, functional adaptations help species to become
      better suited to their ecological niches. From the morphological aspect, these
      adaptations are reflected in the anatomical specializations of different organs.
      Specializations of the lingual organ is a critical adaptation of birds, such as
      the white-headed duck (Oxyura leucocephala), that enables their nutritional
      requirements to be met. For optimal use of the available food resources, the
      white-headed duck utilizes three methods of food collection, namely pecking,
      grazing and filter-feeding. Since this species is classified as endangered, we
      conducted the present study on two carcasses of the white-headed duck (death due
      to natural causes) employing routine histological methods, light microscopy and
      scanning electron microscopy. Our results show that the tongue of this bird
      shares some similarities and some differences with the tongue of other members of
      the family Anatidae. The results confirm that it is better adapted to the filter
      feeding method rather than to other types of food intake. This adaptation is
      reflected by anatomical specializations of its lingual structures, including the
      stair-like outline shape, bi-sectional lingual body, a deep median sulcus,
      lateral conical papillae, mucus secreting glands, lack of serous secreting
      glands, cartilaginous skeleton and the triangular fibromuscular structure of the
      lingual body. The so-called triangular structure and cartilaginous skeleton are
      the major structures involved in the lingual motions during the filter-feeding
      method. The presence of the triangular structure and its connection with the
      cartilaginous skeleton and lingual mucosa have not previously been reported in
      any species of birds.

PMID- 29589226
TI  - Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality,
      and incident type 2 diabetes: a systematic review and dose response meta
      analysis.
AB  - PURPOSE:  To estimate the strength and shape of the dose-response relationship
      between sedentary behaviour and all-cause, cardiovascular disease (CVD) and
      cancer mortality, and incident type 2 diabetes (T2D), adjusted for physical
      activity (PA). Data Sources: Pubmed, Web of Knowledge, Medline, Embase, Cochrane
      Library and Google Scholar (through September-2016); reference lists. Study
      Selection: Prospective studies reporting associations between total daily
      sedentary time or TV viewing time, and >= one outcome of interest. Data
      Extraction: Two independent reviewers extracted data, study quality was assessed;
      corresponding authors were approached where needed. Data Synthesis: Thirty-four
      studies (1,331,468 unique participants; good study quality) covering 8 exposure
      outcome combinations were included. For total sedentary behaviour, the PA
      adjusted relationship was non-linear for all-cause mortality (RR per 1 h/day:
      were 1.01 (1.00-1.01) <= 8 h/day; 1.04 (1.03-1.05) > 8 h/day of exposure), and
      for CVD mortality (1.01 (0.99-1.02) <= 6 h/day; 1.04 (1.03-1.04) > 6 h/day). The
      association was linear (1.01 (1.00-1.01)) with T2D and non-significant with
      cancer mortality. Stronger PA-adjusted associations were found for TV viewing
      (h/day); non-linear for all-cause mortality (1.03 (1.01-1.04) <= 3.5 h/day; 1.06
      (1.05-1.08) > 3.5 h/day) and for CVD mortality (1.02 (0.99-1.04) <= 4 h/day; 1.08
      (1.05-1.12) > 4 h/day). Associations with cancer mortality (1.03 (1.02-1.04)) and
      T2D were linear (1.09 (1.07-1.12)). CONCLUSIONS:  Independent of PA, total
      sitting and TV viewing time are associated with greater risk for several major
      chronic disease outcomes. For all-cause and CVD mortality, a threshold of 6-8
      h/day of total sitting and 3-4 h/day of TV viewing was identified, above which
      the risk is increased.

PMID- 29589228
TI  - Parental Wellbeing, Parenting and Child Development in Ghanaian Families with
      Young Children.
AB  - Approximately one-third of early childhood pupils in Ghana are struggling with
      meeting basic behavioral and developmental milestones, but little is known about
      mechanisms or factors that contribute to poor early childhood development. With a
      lack of developmental research to guide intervention or education program and
      policy planning, this study aimed to address these research gaps by examining a
      developmental mechanism for early childhood development. We tested a mediational
      mechanism model that examined the influence of parental wellbeing on parenting
      and children's development. Two hundred and sixty-two Ghanaian parents whose
      children attended early childhood classes (nursery to 3rd grade) were recruited.
      Data were gathered through parent interviews and Structural Equation Modeling was
      utilized to examine pathways of the model. Results support the mediational model
      that Ghanaian parents' depression was associated with less optimal parenting, and
      in turn greater child externalizing behavioral problems. This study adds new
      evidence of cross cultural consistency in early childhood development.

PMID- 29589229
TI  - Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy.
AB  - Immunotherapy is one of the most exciting recent breakthroughs in the field of
      cancer treatment. Many different approaches are being developed and a number have
      already gained regulatory approval or are under investigation in clinical trials.
      However, learning from the past, preclinical animal models often insufficiently
      reflect the physiological situation in humans, which subsequently causes
      treatment failures in clinical trials. Due to species-specific differences in
      most parts of the immune system, the transfer of knowledge from preclinical
      studies to clinical trials is eminently challenging. Human tumor cell line-based
      or patient-derived xenografts in immunocompromised mice have been successfully
      applied in the preclinical testing of cytotoxic or molecularly targeted agents,
      but naturally these systems lack the human immune system counterpart. The co
      transplantation of human peripheral blood mononuclear cells or hematopoietic stem
      cells is employed to overcome this limitation. This review summarizes some
      important aspects of the different available tumor xenograft mouse models, their
      history, and their implementation in drug development and personalized therapy.
      Moreover, recent progress, opportunities and limitations of different humanized
      mouse models will be discussed.

PMID- 29589231
TI  - Epibulbar osseous choristoma: a photo essay case report.
AB  - PURPOSE: To present the pre-, per- and postoperative features of epibulbar
      osseous choristoma. METHODS: Case description including intraoperative imaging
      and histopathology. RESULTS: A 32-year-old male patient presented with a lesion
      on his right eye, suggestive of an epibulbar dermolipoma. Excision of bony lesion
      was performed and revealed epibulbar osseous choristoma. CONCLUSIONS: Epibulbar
      osseous choristoma is a rare and benign condition which can present with features
      similar to dermolipoma.

PMID- 29589230
TI  - Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation
      and Modeling Analysis.
AB  - INTRODUCTION: Two vaccines against rotavirus gastroenteritis (RVGE) in young
      children, Rotarix and RotaTeq, have been available in Europe since 2006.
      Vaccination against rotaviruses significantly reduces the burden of RVGE, but it
      is also associated with a very small increased risk of intussusception. In a
      benefit-risk analysis, the prevented RVGE burden is weighed against the possible
      excess of intussusception. PURPOSE: The aim was to compare the estimated benefits
      and risks of Rotarix vaccination in France. METHODS: We estimated the benefits
      (vaccine-preventable RVGE hospitalizations and deaths) and risks (vaccine-caused
      intussusception hospitalizations and deaths) following two doses of Rotarix in a
      birth cohort of 791,183 followed for 3-5 years in France. We used data from peer
      reviewed clinical and epidemiological studies or publications, and government
      statistics. RESULTS: Within the total number of French children below 5 years of
      age, we estimate vaccination could prevent a median 11,132 [95% credible interval
      (CI) 7842-14,408] RVGE hospitalizations and 7.43 (95% CI 3.27-14.68) RVGE deaths.
      At the same time, vaccination could cause an average of 6.86 (95% CI 2.25-38.37)
      intussusception hospitalizations and 0.0099 (95% CI 0.0024-0.060) intussusception
      deaths in the entire French birth cohort of infants below 1 year of age.
      Therefore, for every intussusception hospitalization and every intussusception
      death caused by vaccination, 1624 (95% CI 240-5243) RVGE hospitalizations and 743
      (95% CI 93-3723) RVGE deaths are prevented, respectively, by vaccination.
      CONCLUSIONS: The vaccine-prevented RVGE hospitalizations and deaths (benefit)
      greatly outweigh the excess potentially vaccination-related cases of
      intussusception (risk), indicating a favorable benefit-risk balance for Rotarix
      in France.

PMID- 29589232
TI  - Autologous neurosensory retinal free patch transplantation for persistent full
      thickness macular hole.
AB  - PURPOSE: To evaluate anatomical and functional outcomes after autologous
      neurosensory retinal free patch (ANRFP) transplantation for persistent idiopathic
      full-thickness macular hole (iFTMH). METHODS: A 65-year-old woman with persistent
      macular hole in her right eye after previous 27-gauge pars plana vitrectomy with
      internal limiting membrane peeling and long-acting gas tamponade underwent ANRFP
      transplantation. Before surgery, best corrected visual acuity in her right eye
      was 20/800. Optical coherence tomography (OCT) showed a 715-micron-diameter FTMH.
      To treat the persistent FTMH, a small autologous neurosensory retinal patch was
      transplanted and placed inside the macular hole under perfluorocarbon liquids
      (PFCL). PFCL-air exchange was performed, and long-acting gas tamponade was
      carried out. Clinical features of the macular area, visual acuity (VA), fundus
      autofluorescence, microperimetry and OCT were recorded during the 10-month follow
      up. RESULTS: The macular hole appeared successfully closed with retinal patch
      stable and well plugged into the hole during the whole follow-up. VA improved to
      20/100 and microperimetry revealed an increase in mean retinal sensitivity from
      14.7 dB at 1 month to 15.6 dB at 10 months postoperatively. OCT showed a well
      distinguishable retinal patch into the hole 1 month after surgery and a
      completely integrated retinal patch between the retinal layers 10 months
      postoperatively. No intra- and postoperative complications were noticed.
      CONCLUSIONS: ANRFP transplantation may represent an innovative technique for
      persistent iFTMH treatment.

PMID- 29589233
TI  - Environmental impact of rice production based on nitrogen fertilizer use.
AB  - While essential to food production, nitrogen (N) fertilizers in agricultural
      ecosystems are also important sources of environmental pollution nationally and
      globally. The environmental impact of three N fertilization levels (30, 60, and
      90 kg ha-1) plus a non-N control (0 kg ha-1) in growing three rice cultivars (cv.
      Hashemi, cv. Alikazemi, and cv. Khazar) were assessed for 2 years in northern
      Iran, with the methodology of the life cycle assessment (LCA). The impact
      categories evaluated in this study were global warming, acidification,
      terrestrial eutrophication, and depletion of fossil, phosphate, and potassium
      resources. Over cultivars, no use of N fertilizer provided the lowest grain yield
      (2194 kg ha-1), whereas the N rates of 60 and 90 kg ha-1 increased grain yield by
      52.9 and 66.9%, respectively. Over N rates, cv. Khazar produced the highest grain
      yield (3415 kg ha-1) and cv. Hashemi the lowest (2663 kg ha-1). On-farm
      (foreground) emissions were higher than off-farm (background) emissions in most
      impact categories. The maximum value of environmental index (1.33) was observed
      for cv. Hashemi with 90 kg N ha-1, while the minimum value (0.38) was observed
      for cv. Khazar without N fertilization. Moreover, cv. Khazar showed the lowest
      resource depletion index (0.44) with 90 kg N ha-1, whereas cv. Hashemi with no
      use of N showed the maximum value (0.96). Over cultivars, high N rates imposed
      drastic impact to the categories acidification and terrestrial eutrophication.
      However, selection of high-yielding cultivars significantly alleviated the impact
      to most categories. Fertilization that enables optimal yields, in accordance with
      the nutrient requirements of crops, ensures the most efficient land use and
      sustainable rice production.

PMID- 29589234
TI  - Nitrogen fertilizer in combination with an ameliorant mitigated yield-scaled
      greenhouse gas emissions from a coastal saline rice field in southeastern China.
AB  - Coastal saline rice fields play an increasingly important role in rice production
      and associated greenhouse gas (GHG) emissions. However, few studies investigated
      the influences of nitrogen (N) fertilizer and soil ameliorant on GHG emissions
      simultaneously in this region. Thus, a field experiment was established to study
      the effects of different N fertilizers and soil ameliorant on global warming
      potential (GWP) and yield-scaled GHG intensity (GHGI) after accounting for carbon
      dioxide (CO2) equivalent emissions of methane (CH4) and nitrous oxide (N2O),
      agrochemical inputs, and farm operations along with agronomic nitrogen use
      efficiency (NUE) during the rice season of 2016 in a coastal saline paddy in
      Lianyungang, China. The experiment was initiated with four N treatments (N0, no
      N; Nu, urea; Nm, organic-inorganic mixed fertilizer; Nw, organic fertilizer made
      from wheat straw) and two ameliorant (A) treatments (A0, no ameliorant; A1, 22.5
      kg ha-1 ameliorant). The results showed that three N fertilizers significantly
      increased the CH4 emissions, N2O emissions, GWP, and grain yield by 42.2% (p <
      0.001), 57.1% (p < 0.001), 49.8% (p < 0.001), and 58.9% (p < 0.001),
      respectively. NuA1, NmA1, and NwA1 treatments obviously reduced the yield-scaled
      GHGI by 21.3%, 16.3%, and 12.4%, respectively, relative to the corresponding
      NuA0, NmA0, and NwA0 treatments. Overall, although three N fertilizers would
      increase the GWP, combining an ameliorant amendment with N fertilizer can
      effectively reduce the yield-scaled GHGI and meanwhile increase the grain yield,
      particularly the NmA1 strategy.

PMID- 29589236
TI  - Correction to: Histological liver chances in Swiss mice caused by tannery
      effluent.
AB  - There is a problem in the original publication of this paper (Figure 2 Graphs are
      in Portuguese). Shown in this paper is the correct version.

PMID- 29589235
TI  - Attenuating effects of caffeic acid phenethyl ester and betaine on abamectin
      induced hepatotoxicity and nephrotoxicity.
AB  - Abamectin (ABM) is a widely utilized potent anthelmintic and insecticidal agent.
      In this study, we investigated the protective effects of caffeic acid phenethyl
      ester (CAPE) and betaine (BET) against ABM-induced hepatotoxicity and
      nephrotoxicity in rats. Forty rats were divided into five groups, receiving
      either oral saline solution (normal control), oral ABM at a dose of 2 mg/kg BW
      (1/5 LD50), CAPE (10 MUmol/kg BW intraperitoneally) followed by ABM, or BET
      supplementation at a dose of 250 mg/kg BW followed by ABM administration, while
      group V rats received a combination of i.p. CAPE and oral BET in the same doses
      before receiving ABM. Biochemical analysis showed that ABM administration
      significantly (p < 0.05) increased serum levels of aminotransferases, alkaline
      phosphatase, lactate dehydrogenase, and cholesterol, as well as serum creatinine
      and urea. Compared to the control group, ABM-intoxicated rats had significantly
      (p < 0.05) higher tissue concentrations of nitric oxide and malondialdehyde, as
      well as lower tissue glutathione concentration, total antioxidant capacity, and
      antioxidant enzymatic activity (glutathione peroxidase, superoxide dismutase, and
      catalase). Histopathological examination of hepatic and renal tissues of ABM
      intoxicated rats showed acute inflammatory and necrotic changes. Pretreatment
      with CAPE and/or BET reversed the biochemical and histopathological alterations
      of ABM on the liver and kidneys. Therefore, CAPE and BET (alone or in
      combination) could be promising protective agents against ABM-induced
      hepatotoxicity and nephrotoxicity. Future studies should confirm our findings and
      evaluate the other molecular effects are involved in the combination
      chemoprotection of CAPE and BET.

PMID- 29589237
TI  - Khuzestan dust phenomenon: a content analysis of most widely circulated
      newspapers.
AB  - Dust is an atmospheric phenomenon that causes adverse environmental effects. It
      is deemed to have harmful effects on health, economics, and climate. This study
      aimed to analyze the content published on the phenomenon of dust in the widely
      circulated newspapers in Iran. We investigated the content of all national and
      provincial newspapers that were published between July and August 2014. Data on
      the materials related to the dust phenomenon in the newspapers were categorized
      and coded. From a total of 510 newspaper issues, 143 articles were devoted to the
      dust phenomenon which 74.1% of them were published in provincial newspapers.
      Among the national newspapers, Hamshahri newspaper with 16 headlines and from the
      provincial newspapers; Karoon with 23 headlines published the highest number of
      articles on dust phenomenon. 45.5% of content on dust were printed on the first
      page of the newspapers. The most common approach to the type of content published
      in these newspapers was an interview. Moreover, we noticed that 28.7% of the
      content published in the newspapers was related to the health issue. The media
      plays an important role in the transmission of health information. Weaknesses in
      addressing the causes of dust occurrence and also in providing solutions for the
      dust control and prevention were noticeable in the content published in the
      newspaper. It seems necessary to take practical measures to disseminate relevant
      information to dust and also address the needs of the target audience community
      influenced by the dust phenomenon properly.

PMID- 29589238
TI  - Approximation of personal exposure to fine particulate matters (PM2.5) during
      cooking using solid biomass fuels in the kitchens of rural West Bengal, India.
AB  - More than 85% of the rural Indian households use traditional solid biofuels
      (SBFs) for daily cooking. Burning of the easily available unprocessed solid fuels
      in inefficient earthen cooking stoves produce large quantities of particulate
      matters. Smaller particulates, especially with aerodynamic diameter of 2.5 MUm or
      less (PM2.5), largely generated during cooking, are considered to be health
      damaging in nature. In the present study, kitchen level exposure of women cooks
      to fine particulate matters during lunch preparation was assessed considering
      kitchen openness as surrogate to the ventilation condition. Two-way ANCOVA
      analysis considering meal quantity as a covariate revealed no significant
      interaction between the openness and the seasons explaining the variability of
      the personal exposure to the fine particulate matters in rural kitchen during
      cooking. Multiple linear regression analysis revealed the openness as the only
      significant predictor for personal exposure to the fine particulate matters. In
      the present study, the annual average fine particulate matter exposure
      concentration was found to be 974 MUg m-3.

PMID- 29589239
TI  - Phthalate exposure and high blood pressure in adults: a cross-sectional study in
      China.
AB  - Widespread phthalate exposure has been recently documented and is hypothesized to
      increase blood pressure (BP) in humans. However, current studies have provided
      inconclusive evidence for an association between phthalate exposure and BP. Human
      epidemiologic studies on the topic remain lacking. Therefore, this study aims to
      examine the association between serum phthalate concentrations and BP in a
      Chinese population. We measured several parameters of BP (systolic BP, diastolic
      BP, total cholesterol, and triglyceride) and the concentrations of 16 phthalates
      (dimethyl phthalate (DMP), diethyl phthalate, diisobutyl phthalate, dibutyl
      phthalate (DBP), bis (2-methoxyethyl) phthalate, bis (4-methyl-2-pentyl)
      phthalate, bis (2-ethoxyethyl) phthalate, diamyl phthalate, dihexyl phthalate,
      benzyl butyl phthalate, bis (2-nbutoxyethyl) phthalate (DBEP), dicyclohexyl
      phthalate, bis (2-ethyl hexyl) phthalate (DEHP), diisononyl phthalate, diphenyl
      phthalate, and di-n-octyl phthalate) in the serum of 474 adults recruited from a
      primary health care clinic. The relationship between serum phthalate
      concentrations and BP parameters was assessed with multivariate linear
      regressions. DBP was the most ubiquitous and dominant contaminant in the study
      population. The systolic BP of subjects in the median-exposure DEHP group
      significantly increased by 2.96 mmHg (p < 0.05) relative to that of subjects in
      the low-exposure group. Significant positive dose-related associations of DMP and
      DBEP with the levels of total cholesterol in serum (p for trend < 0.05) were also
      found. These associations persisted even when considering exposure to multiple
      phthalates. Our results suggested that phthalate exposure might increase BP in
      adults. However, our findings warrant further studies in a larger and more
      general population.

PMID- 29589241
TI  - Redox buffering and de-coupling of arsenic and iron in reducing aquifers across
      the Red River Delta, Vietnam, and conceptual model of de-coupling processes.
AB  - Analysis of over 500 groundwater samples from throughout the Red River Delta
      indicates de-coupling of dissolved arsenic (As) and dissolved iron (Fe). Sorting
      of all data along the redox potentials suggests re-adsorption of As released
      initially from Mn(IV)-oxyhydroxides and later from Fe(III)-oxyhydroxides on
      remaining ferric phases at moderate redox levels. A gradually decreasing specific
      surface area available for re-adsorption of As probably plays a role as a
      consequence of limited reactivity of more crystalline phases such as goethite and
      hematite. At low redox levels, concentrations of Fe and phosphate decrease, but
      As concentrations keep increasing and most As is present as As(III) with limited
      adsorption affinity. Based on the results of speciation modeling, the water is
      supersaturated with respect to siderite and vivianite. A general conceptual model
      of As and Fe behavior is presented, suggesting that coupled behavior is possible
      in two geochemical "windows", i.e., 1: between saturation of remaining adsorption
      sites and the onset of siderite and vivianite precipitation, and 2: after the
      beginning of secondary sulfide phases precipitation and during methanogenesis.
      The de-coupling of As from Fe is common and has been observed at many sites
      around the world where As is released as a consequence of redox processes, e.g.,
      in Bangladesh, West Bengal and Assam in India, the Mekong Delta in Cambodia and
      Vietnam, and Taiwan. The presented general conceptual model of de-coupling
      processes can be applied to the interpretation of As and Fe data, and, thus, it
      can help in the preparation of a site conceptual model which is a necessary
      prerequisite for reactive transport modeling.

PMID- 29589240
TI  - Evaluating toxicity of copper(II) oxide nanoparticles (CuO-NPs) through
      waterborne exposure to tilapia (Oreochromis mossambicus) by tissue accumulation,
      oxidative stress, histopathology, and genotoxicity.
AB  - Metal oxide nanoparticles are widely used in industries, and peak level can be
      confirmed in their surroundings. In the present study, the sub-lethal effects of
      CuO-NPs from low to high concentration as 0.5 to 1.5 mg/L were observed in
      tilapia (Oreochromis mossambicus). Accumulation of copper from CuO-NPs was
      increased with the increase in doses, and maximum accumulation was found in the
      gill than liver and muscles. The increased lipid peroxidation level was observed
      in the gill as compared to liver, and the similar results were obtained in
      catalase and glutathione while superoxide dismutase level was higher in the liver
      than gills. In histological alterations, gill edema, curved tips, fusion of gill
      lamellae, and thickening of primary and secondary gill lamellae were observed.
      Necrosis and apoptosis with condensed nuclear bodies and pyknotic nuclei were
      observed in the liver at the highest dose concentration. In a genotoxic study,
      the highest value of % tail DNA and olive tail movement was observed with
      increasing concentrations. Copper oxide nanoparticles has greater potential to
      accumulate in the soft tissues, which may cause respiratory distress such as
      oxidative stress, induction of antioxidant defense by raising glutathione, organ
      pathology, and genotoxicity.

PMID- 29589242
TI  - Evaluation of iron loading in four types of hepatopancreatic cells of the
      mangrove crab Ucides cordatus using ferrocene derivatives and iron supplements.
AB  - The mangrove crab Ucides cordatus is a bioindicator of aquatic contamination. In
      this work, the iron availability and redox activity of saccharide-coated mineral
      iron supplements (for both human and veterinary use) and ferrocene derivatives in
      Saline Ucides Buffer (SUB) medium were assessed. The transport of these
      metallodrugs by four different hepatopancreatic cell types (embryonic (E),
      resorptive (R), fibrillar (F), and blister (B)) of U. cordatus were measured.
      Organic coated iron minerals (iron supplements) were stable against strong
      chelators (calcein and transferrin). Ascorbic acid efficiently mediated the
      release of iron only from ferrocene compounds, leading to redox-active species.
      Ferrous iron and iron supplements were efficient in loading iron to all
      hepatopancreatic cell types. In contrast, ferrocene derivatives were loaded only
      in F and B cell types. Acute exposition to the iron compounds resulted in cell
      viability of 70-95%, and to intracellular iron levels as high as 0.40 MUmol L-1
      depending upon the compound and the cell line. The easiness that iron from iron
      metallodrugs was loaded/transported into U. cordatus hepatopancreatic cells
      reinforces a cautionary approach to the widespread disposal and use of highly
      bioavailable iron species as far as the long-term environmental welfare is
      concerned.

PMID- 29589243
TI  - Characterization and phenanthrene sorption of organic matter fractions isolated
      from organic and mineral soils.
AB  - Sorption of phenanthrene (PHE) to humic acid (HA) and humin (HM) fractions
      isolated from organic and mineral soils was investigated to better understand
      sorption processes in varying soil types. Samples were characterized by elemental
      analysis, X-ray photoelectron spectroscopy, 13C nuclear magnetic resonance, and
      CO2 adsorption. No clear correlation was found between the distribution
      coefficient (Kd) and the bulk polarity of the soil organic matters (SOMs). By
      contrast, PHE Kd values generally increased with increasing surface polarity of
      the tested SOMs, implying that surface polarity may play a more important role in
      PHE sorption than the bulk one. The organic carbon (OC)-normalized Kd values
      (Koc) of HMs were higher than those of HAs as a result of the higher aliphatic C
      contents of HMs. For SOMs isolated from mineral soil (MI-SOMs), part of the
      aliphatic domains may be tightly associated with minerals and were not accessible
      to PHE molecules, resulting in lower PHE Koc values of MI-SOMs than the
      corresponding fractions extracted from the organic soil. This study implies that
      both chemical characteristics and physical conformation of SOMs are paramount
      considerations when investigating sorption process of hydrophobic organic
      compounds in soils.

PMID- 29589244
TI  - Performance and mechanisms of thermally treated bentonite for enhanced phosphate
      removal from wastewater.
AB  - Optimization of clays as adsorbent for low concentration phosphorus removal from
      wastewater has received increasing attention in recent years. This study explored
      the feasibility of using bentonite as an adsorbent for phosphate (P) removal from
      synthetic wastewater, by assessing the performance of thermally treated bentonite
      for P removal and elucidating the mechanisms of P adsorption. Natural bentonite
      (B25) was thermally treated at 100-1000  degrees C (B100-B1000) for 2 h. Physical
      and chemical properties were measured by the SEM, XRD, pore size distribution,
      EDX, and cation exchange capacity (CEC) methods. Thermal treatment increased P
      sorption capacity of bentonite and that B800 had a higher P sorption capacity
      (6.94 mg/g) than B25 (0.237 mg/g) and B400 (0.483 mg/g) using the Langmuir
      isotherm equation. Study of sorption kinetics indicated that B800 rapidly removed
      94% of P from a 10 mg P/L solution and the pseudo-second-order equation fitted
      the data well. The Ca2+ release capacity of B800 (1.31 mg/g) was significantly
      higher than that of B25 (0.29 mg/g) and B400 (0.40 mg/g) (p < 0.05). The initial
      pH level had a smaller impact on P removal efficiency for B800 than that of B25
      and B400. Ca-P was the main fraction of P adsorbed onto B800, and Ca10-P was the
      main species (41.4%). The main factors affecting the phosphorous adsorption
      capacity of B800 were changed crystal structure, strong calcium release capacity,
      and improved stability in different pH solutions. The results demonstrated that
      thermally treated bentonite (B800) has the potential to be an efficient adsorbent
      for removal of low-concentration phosphorus from wastewater.

PMID- 29589246
TI  - Treatment of municipal sludge by Fenton oxidation combined vacuum preloading.
AB  - Municipal sludge, composed of numerous types of organic matter with a gel
      structure, has high water content, low permeability coefficient, and poor
      mechanical properties. Fenton oxidation-assisted vacuum preloading method for
      municipal sludge treatment was proposed. First, the municipal sludge was oxidized
      and treated with Fenton's reagent; then, drainage consolidation was performed on
      the sludge with the vacuum preloading method. The optimal dosage of Fenton's
      reagent for municipal sludge was determined. Comparative experiments of the one
      dimensional consolidation of municipal sludge treated with Fenton's reagent and
      the drainage consolidation by Fenton oxidation-assisted vacuum preloading were
      conducted. The results reveal that the specific resistance of municipal sludge
      decreases upon Fenton oxidation by approximately 98.6% at the optimal dosage of
      22%, sludge water content decreases from 82.14 to 66.67%, volume reduces by ~
      40%, and unconfined compressive strength increases to 55 kPa.

PMID- 29589245
TI  - Life cycle of PCBs and contamination of the environment and of food products from
      animal origin.
AB  - This report gives a summary of the historic use, former management and current
      release of polychlorinated biphenyls (PCBs) in Germany and assesses the impact of
      the life cycle of PCBs on the contamination of the environment and of food
      products of animal origin. In Germany 60,000 t of PCBs were used in transformers,
      capacitors or as hydraulic oils. The use of PCB oils in these "closed
      applications", has been banned in Germany in 2000. Thirty to 50% of these PCBs
      were not appropriately managed. In West Germany, 24,000 t of PCBs were used in
      open applications, mainly as additive (plasticiser, flame retardant) in sealants
      and paints in buildings and other construction. The continued use in open
      applications has not been banned, and in 2013, an estimated more than 12,000 t of
      PCBs were still present in buildings and other constructions. These open PCB
      applications continuously emit PCBs into the environment with an estimated
      release of 7-12 t per year. This amount is in agreement with deposition
      measurements (estimated to 18 t) and emission estimates for Switzerland. The
      atmospheric PCB releases still have an relevant impact on vegetation and
      livestock feed. In addition, PCBs in open applications on farms are still a
      sources of contamination for farmed animals. Furthermore, the historic
      production, use, recycling and disposal of PCBs have contaminated soils along the
      lifecycle. This legacy of contaminated soils and contaminated feed, individually
      or collectively, can lead to exceedance of maximum levels in food products from
      animals. In beef and chicken, soil levels of 5 ng PCB-TEQ/kg and for chicken with
      high soil exposure even 2 ng PCB-TEQ/kg can lead to exceedance of EU limits in
      meat and eggs. Areas at and around industries having produced or used or managed
      PCBs, or facilities and areas where PCBs were disposed need to be assessed in
      respect to potential contamination of food-producing animals. For a large share
      of impacted land, management measures applicable on farm level might be
      sufficient to continue with food production. Open PCB applications need to be
      inventoried and better managed. Other persistent and toxic chemicals used as
      alternatives to PCBs, e.g. short chain chlorinated paraffins (SCCPs), should be
      assessed in the life cycle for exposure of food-producing animals and humans.

PMID- 29589247
TI  - Element uptake and physiological responses of Lactuca sativa upon co-exposures to
      tourmaline and dissolved humic acids.
AB  - Element migration and physiological response in Lactuca sativa upon co-exposure
      to tourmaline (T) and dissolved humic acids (DHAs) were investigated. Different
      fractions of DHA1 and DHA4 and three different doses of T were introduced into
      Hoagland's solution. The results indicated that T enhanced the contents of
      elements such as N and C, Si and Al in the roots and shoots. The correlation
      between TF values of Si and Al (R2 = 0.7387) was higher than that of Si and Mn
      (R2 = 0.4961) without the presence of DHAs. However, both DHA1 and DHA4 increased
      the correlation between Si and Mn, but decreased the one between Si and Al. CAT
      activities in T treatments were positively correlated to the contents of N and Al
      in the shoots, whose R 2 was 0.9994 and 0.9897, respectively. In the co-exposure
      of DHAs and tourmaline, DHA4 exhibited more impacts on element uptake, CAT
      activities, as well as ABA contents in comparison with the presence of DHA1,
      regardless of the T exposure doses. These results suggested that DHAs have
      effects on mineral element behaviors and physiological response in Lactuca sativa
      upon exposure to tourmaline for the first time, which had great use in guiding
      soil remediation.

PMID- 29589248
TI  - Characterization of CDOM absorption of reservoirs with its linkage of regions and
      ages across China.
AB  - The absorption of chromophoric dissolved organic matter (CDOM) is an important
      part of light absorptions in aquatic systems. The increasing eutrophication of
      reservoirs and regional characteristics would affect the CDOM properties
      sensitively which would be important for the application of remote sensing
      monitoring. The highest (4.07 +/- 2.31 m-1) and lowest (0.79 +/- 0.67 m-1) CDOM
      concentrations of reservoirs were observed in the northeastern lake region (NER)
      and Tibetan Plateau lake region (TPR), respectively. The differences between S275
      295 among the five lake regions were significant (p < 0.05) in which the steepest
      S275-295 (0.0173 +/- 0.0026 nm-1) was observed in TPR and the shallowest (0.0326
      +/- 0.0152 nm-1) in Yungui Plateau lake region (YGR). The strong relationships
      between aCDOM(355) and DOC appeared in the NER (R2 = 0.43), eastern lake region
      (EAR) (R2 = 0.69), Mengxin lake region (MXR) (R2 = 0.61), and YGR (R2 = 0.79)
      which would be a good proxy for DOC in regional reservoirs. Most of all, the
      correlation between reservoir's establishing time and CDOM absorption under
      oligotrophic states was relatively strong in the EAR and MXR regions. It
      indicated that the establishing time of reservoirs affected the CDOM absorption
      to some extent under the oligotrophic states without much human disturbance. Our
      results indicate CDOM absorption varies with regions, and the relationships
      between CDOM and DOC are variable for different regions. Therefore, DOC
      estimation in reservoirs through CDOM absorption needs to be considered according
      to lake regions and trophic states.

PMID- 29589249
TI  - Rural-urban disparities in the utilization of mental health inpatient services in
      China: the role of health insurance.
AB  - Reducing rural-urban disparities in health and health care has been a key policy
      goal for the Chinese government. With mental health becoming an increasingly
      significant public health issue in China, empirical evidence of disparities in
      the use of mental health services can guide steps to reduce them. We conducted
      this study to inform China's on-going health-care reform through examining how
      health insurance might reduce rural-urban disparities in the utilization of
      mental health inpatient services in China. This retrospective study used 10 years
      (2005-2014) of hospital electronic health records from the Shandong Center for
      Mental Health and the DaiZhuang Psychiatric Hospital, two major psychiatric
      hospitals in Shandong Province. Health insurance was measured using types of
      health insurance and the actual reimbursement ratio (RR). Utilization of mental
      health inpatient services was measured by hospitalization cost, length of stay
      (LOS), and frequency of hospitalization. We examined rural-urban disparities in
      the use of mental health services, as well as the role of health insurance in
      reducing such disparities. Hospitalization costs, LOS, and frequency of
      hospitalization were all found to be lower among rural than among urban
      inpatients. Having health insurance and benefiting from a relatively high RR were
      found to be significantly associated with a greater utilization of inpatient
      services, among both urban and rural residents. In addition, an increase in the
      RR was found to be significantly associated with an increase in the use of mental
      health services among rural patients. Consistent with the existing literature,
      our study suggests that increasing insurance schemes' reimbursement levels could
      lead to substantial increases in the use of mental health inpatient services
      among rural patients, and a reduction in rural-urban disparities in service
      utilization. In order to promote mental health care and reduce rural-urban
      disparities in its utilization in China, improving rural health insurance
      coverage (e.g., reducing the coinsurance rate) would be a powerful policy
      instrument.

PMID- 29589250
TI  - Novel cationic supersaturable nanomicellar systems of raloxifene hydrochloride
      with enhanced biopharmaceutical attributes.
AB  - The work describes systematic development of nanomicellar cationic supersaturable
      self-nanoemulsifying drug delivery systems (CS-SNEDDS) for augmenting oral
      biopharmaceutical performance of raloxifene hydrochloride. Plain SNEDDS
      formulation containing Capryol 90, Cremophor RH 40, and Transcutol HP was
      optimized using D-optimal mixture design. SNEDDS were characterized for
      emulsification time, globule size, in vitro drug release, and ex vivo permeation.
      The CS-SNEDDS formulation was prepared from the optimized SNEDDS by adding
      oleylamine as the cationic charge inducer and HPMC as the polymeric precipitation
      inhibitor. Evaluation of CS-SNEDDS was carried out through in vitro cell line
      studies on Caco-2 and MCF-7 cells, in situ perfusion, and in vivo pharmacokinetic
      studies, which indicated significant improvement in biopharmaceutical attributes
      of the drug from CS-SNEDDS over plain drug.

PMID- 29589251
TI  - Hepatocellular adenoma in a woman who was undergoing testosterone treatment for
      gender identity disorder.
AB  - A 32-year-old Japanese woman was admitted to our hospital for the diagnosis and
      treatment of multiple liver tumors. She had been receiving 125 mg testosterone
      enanthate every 2 weeks following female-to-male gender identity disorder (GID)
      diagnosis at 20 years of age. Ultrasonography, computed tomography, and magnetic
      resonance imaging showed 11 hepatic nodular tumors with a maximum diameter of 28
      mm. Liver tumors with hepatocellular adenoma (HCA) were diagnosed with needle
      biopsy. Segmentectomy of the left lateral lobe including two lesions,
      subsegmentectomy of S6 including two lesions, enucleation of each tumor in S5 and
      S7, and open surgical radiofrequency ablation for each tumor in S4 and S7 were
      performed. Immunohistochemical specimens showed that the tumor cells were
      diffusely and strongly positive for glutamine synthetase and that the nuclei were
      ectopically positive for beta-catenin. Thus, the tumors were diagnosed as beta
      catenin-activated HCA (b-HCA). Transcatheter arterial chemoembolization plus
      subsequent radiofrequency ablation was performed for the 3 residual lesions in S4
      and S8. Although testosterone enanthate was being continued for GID, no
      recurrence was observed until at least 22 months after the intensive treatments.
      HCA development in such patients receiving testosterone should be closely
      monitored using image inspection.

PMID- 29589252
TI  - The role of phase shifts of sensory inputs in walking revealed by means of phase
      reduction.
AB  - Detailed neural network models of animal locomotion are important means to
      understand the underlying mechanisms that control the coordinated movement of
      individual limbs. Daun-Gruhn and Toth, Journal of Computational Neuroscience
      31(2), 43-60 (2011) constructed an inter-segmental network model of stick insect
      locomotion consisting of three interconnected central pattern generators (CPGs)
      that are associated with the protraction-retraction movements of the front,
      middle and hind leg. This model could reproduce the basic locomotion coordination
      patterns, such as tri- and tetrapod, and the transitions between them. However,
      the analysis of such a system is a formidable task because of its large number of
      variables and parameters. In this study, we employed phase reduction and
      averaging theory to this large network model in order to reduce it to a system of
      coupled phase oscillators. This enabled us to analyze the complex behavior of the
      system in a reduced parameter space. In this paper, we show that the reduced
      model reproduces the results of the original model. By analyzing the interaction
      of just two coupled phase oscillators, we found that the neighboring CPGs could
      operate within distinct regimes, depending on the phase shift between the sensory
      inputs from the extremities and the phases of the individual CPGs. We demonstrate
      that this dependence is essential to produce different coordination patterns and
      the transition between them. Additionally, applying averaging theory to the
      system of all three phase oscillators, we calculate the stable fixed points -
      they correspond to stable tripod or tetrapod coordination patterns and identify
      two ways of transition between them.

PMID- 29589253
TI  - Needle breakage during an inferior alveolar nerve block in a child with KBG
      syndrome: A case report.
AB  - BACKGROUND: Needle breakage during the administration of dental analgesia is an
      extremely rare event. CASE REPORT: A case of needle breakage during the
      administration of an inferior alveolar nerve block occurred in a child with KBG
      syndrome. During the injection, a sudden movement of the child caused the
      breakage of the needle. The next day, the retrieval of the needle was performed
      surgically under general analgesia. FOLLOW-UP: Three months after the surgery the
      healing was good. Two years later the child underwent a dental extraction with
      the aid of nitrous oxide/oxygen analgesia/anxiolysis. CONCLUSION: Needle fracture
      is a possible event during the administration of dental analgesia in children.

PMID- 29589255
TI  - Phylogenetic Flexibility via Hall-Type Inequalities and Submodularity.
AB  - Given a collection [Formula: see text] of subsets of a finite set X, we say that
      [Formula: see text] is phylogenetically flexible if, for any collection R of
      rooted phylogenetic trees whose leaf sets comprise the collection [Formula: see
      text], R is compatible (i.e. there is a rooted phylogenetic X-tree that displays
      each tree in R). We show that [Formula: see text] is phylogenetically flexible if
      and only if it satisfies a Hall-type inequality condition of being 'slim'. Using
      submodularity arguments, we show that there is a polynomial-time algorithm for
      determining whether or not [Formula: see text] is slim. This 'slim' condition
      reduces to a simpler inequality in the case where all of the sets in [Formula:
      see text] have size 3, a property we call 'thin'. Thin sets were recently shown
      to be equivalent to the existence of an (unrooted) tree for which the median
      function provides an injective mapping to its vertex set; we show here that the
      unrooted tree in this representation can always be chosen to be a caterpillar
      tree. We also characterise when a collection [Formula: see text] of subsets of
      size 2 is thin (in terms of the flexibility of total orders rather than
      phylogenies) and show that this holds if and only if an associated bipartite
      graph is a forest. The significance of our results for phylogenetics is in
      providing precise and efficiently verifiable conditions under which supertree
      methods that require consistent inputs of trees can be applied to any input trees
      on given subsets of species.

PMID- 29589254
TI  - Juniperonic Acid Incorporation into the Phospholipids of Murine Macrophage Cells
      Modulates Pro-Inflammatory Mediator Production.
AB  - Juniperonic acid (JPA; Delta5,11,14,17-20:4), originally identified in certain
      gymnosperm seeds, is a rare n-3 polyunsaturated fatty acid (PUFA) with lipid
      modulating effects on rats and anti-proliferative effects on fibroblast cell
      proliferation. However, little is known how JPA exerted its immunosuppressive
      effect. The objective of this study was to investigate whether JPA inhibited the
      production of inflammatory mediators through the modulation of cellular
      phospholipid fatty acid compositions. Using standard lipid chemistry techniques
      in conjunction with argentated column chromatography, high-purity JPA (> 98%) was
      extracted, isolated, and purified from Biota kernels. When murine RAW264.7
      macrophages were incubated with increasing concentrations of JPA, amounts of
      cellular phospholipid total PUFA, JPA, and Delta7-docosatetraenoic acid (Delta7
      DTA; elongation product of JPA) increased in a dose-dependent manner; however,
      the proportions of total monounsaturated fatty acid (MUFA) and arachidonic acid
      (AA) decreased. JPA suppressed the production of nitric oxide (NO), interleukin-6
      (IL-6), and tumor necrosis factor-alpha (TNF-alpha) and the expression of
      inducible nitric oxide synthase (iNOS) up to 21, 75, 30, and 44%, respectively.
      The induction of cyclooxygenase-2 (COX-2) over-expression by JPA could account
      for the doubling of the PGE2 level. Furthermore, JPA suppressed the expression of
      phosphorylated mitogen-activated protein kinases (MAPK). In a separate study
      using the mouse ear edema model, we demonstrated that JPA also significantly
      suppressed inflammation, as measured by ear thickness and biopsy weight. The anti
      inflammatory properties of JPA could be due, in part, to the incorporation of JPA
      into cellular phospholipids with subsequent modulation of membrane-mediated MAPK
      signaling.

PMID- 29589256
TI  - Use of the mtrR Gene for Rapid Molecular Diagnosis of Neisseria gonorrhoeae and
      Identification of the Reduction of Susceptibility to Antibiotics in Endocervical
      Swabs.
AB  - BACKGROUND: Neisseria gonorrhoeae is one of the main etiological agents of
      sexually transmitted diseases. The asymptomatic course of the infection and its
      resistance to antibiotics can lead to pelvic inflammatory disease and
      infertility. OBJECTIVES: We developed a polymerase chain reaction (PCR) test
      using the methyltetrahydrofolate homocysteine methyltransferase reductase (mtrR)
      gene to identify N. gonorrhoeae and detect reduced susceptibility to antibiotics.
      MATERIAL AND METHODS: We analysed 250 samples of endocervical exudate from
      infertile women with a negative diagnosis of N. gonorrhoeae. We designed NGmtr
      primers to detect N. gonorrhoeae and identify the antibiotic-resistant strain.
      RESULTS: Of the 250 samples, 60 (24%) tested positive for N. gonorrhoeae using
      real-time PCR. Our study was validated using the HO primers and the Seeplex STD6
      ACE System, with a 100% correlation. Furthermore, the NGmtr primers are specific
      for N. gonorrhoeae and not for other species. Additionally, the curves generated
      by real-time PCR differed between wild and variant strains (10.93%). The
      dissociation temperatures for the wild and variant strains were 86.5 and 89 
      degrees C, respectively. CONCLUSIONS: The NGmtr primers enabled us to identify N.
      gonorrhoeae strains with or without reduction of susceptibility to antibiotics.
      Therefore, this work constitutes a tool that will facilitate the diagnosis of
      this infection for a low cost and improve patient quality of life.

PMID- 29589257
TI  - To protect or not to protect: examining reasons for sun protection among young
      women at risk for skin cancer.
AB  - We aimed to further the understanding of the low rates of sun protection in young
      women at risk for skin cancer. Six-hundred-sixty-one daily diary entries were
      received via text message over 14 days from 56 young women at moderate to high
      risk of developing skin cancer. Women reported whether or not they used sun
      protection and also listed what their reasons were for using protection or not
      using sun protection each day. Multi-level modeling was used to examine the
      influence of study variables when predicting daily sun protection or lack of
      protection. The number of days in which sun protection was reported was
      positively associated with "habit" and "prevention" as reasons for protection and
      negatively associated with "not-needed" and "unprepared" as reasons for non
      protection. Self-reported sun protection increased over the 14-day study period.
      Results of this study suggest the potential value of interventions aimed at
      motives for sun-protection behaviors.

PMID- 29589258
TI  - Toward a real-time system for temporal enhanced ultrasound-guided prostate
      biopsy.
AB  - PURPOSE: We have previously proposed temporal enhanced ultrasound (TeUS) as a new
      paradigm for tissue characterization. TeUS is based on analyzing a sequence of
      ultrasound data with deep learning and has been demonstrated to be successful for
      detection of cancer in ultrasound-guided prostate biopsy. Our aim is to enable
      the dissemination of this technology to the community for large-scale clinical
      validation. METHODS: In this paper, we present a unified software framework
      demonstrating near-real-time analysis of ultrasound data stream using a deep
      learning solution. The system integrates ultrasound imaging hardware,
      visualization and a deep learning back-end to build an accessible, flexible and
      robust platform. A client-server approach is used in order to run computationally
      expensive algorithms in parallel. We demonstrate the efficacy of the framework
      using two applications as case studies. First, we show that prostate cancer
      detection using near-real-time analysis of RF and B-mode TeUS data and deep
      learning is feasible. Second, we present real-time segmentation of ultrasound
      prostate data using an integrated deep learning solution. RESULTS: The system is
      evaluated for cancer detection accuracy on ultrasound data obtained from a large
      clinical study with 255 biopsy cores from 157 subjects. It is further assessed
      with an independent dataset with 21 biopsy targets from six subjects. In the
      first study, we achieve area under the curve, sensitivity, specificity and
      accuracy of 0.94, 0.77, 0.94 and 0.92, respectively, for the detection of
      prostate cancer. In the second study, we achieve an AUC of 0.85. CONCLUSION: Our
      results suggest that TeUS-guided biopsy can be potentially effective for the
      detection of prostate cancer.

PMID- 29589259
TI  - Prostate segmentation in transrectal ultrasound using magnetic resonance imaging
      priors.
AB  - PURPOSE: In the current standard of care, real-time transrectal ultrasound (TRUS)
      is commonly used for prostate brachytherapy guidance. As TRUS provides limited
      soft tissue contrast, segmenting the prostate gland in TRUS images is often
      challenging and subject to inter-observer and intra-observer variability,
      especially at the base and apex where the gland boundary is hard to define.
      Magnetic resonance imaging (MRI) has higher soft tissue contrast allowing the
      prostate to be contoured easily. In this paper, we aim to show that prostate
      segmentation in TRUS images informed by MRI priors can improve on prostate
      segmentation that relies only on TRUS images. METHODS: First, we compare the TRUS
      based prostate segmentation used in the treatment of 598 patients with a high
      quality MRI prostate atlas and observe inconsistencies at the apex and base.
      Second, motivated by this finding, we propose an alternative TRUS segmentation
      technique that is fully automatic and uses MRI priors. The algorithm uses a
      convolutional neural network to segment the prostate in TRUS images at mid-gland,
      where the gland boundary can be clearly seen. It then reconstructs the gland
      boundary at the apex and base with the aid of a statistical shape model built
      from an MRI atlas of 78 patients. RESULTS: Compared to the clinical TRUS
      segmentation, our method achieves similar mid-gland segmentation results in the
      598-patient database. For the seven patients who had both TRUS and MRI, our
      method achieved more accurate segmentation of the base and apex with the MRI
      segmentation used as ground truth. CONCLUSION: Our results suggest that utilizing
      MRI priors in TRUS prostate segmentation could potentially improve the
      performance at base and apex.

PMID- 29589260
TI  - Real-time inextensible surgical thread simulation.
AB  - PURPOSE: This paper discusses a real-time simulation method of inextensible
      surgical thread based on the Cosserat rod theory using position-based dynamics
      (PBD). The method realizes stable twining and knotting of surgical thread while
      including inextensibility, bending, twisting and coupling effects. METHODS: The
      Cosserat rod theory is used to model the nonlinear elastic behavior of surgical
      thread. The surgical thread model is solved with PBD to achieve a real-time,
      extremely stable simulation. Due to the one-dimensional linear structure of
      surgical thread, the direct solution of the distance constraint based on
      tridiagonal matrix algorithm is used to enhance stretching resistance in every
      constraint projection iteration. In addition, continuous collision detection and
      collision response guarantee a large time step and high performance. Furthermore,
      friction is integrated into the constraint projection process to stabilize the
      twining of multiple threads and complex contact situations. RESULTS: Through
      comparisons with existing methods, the surgical thread maintains constant length
      under large deformation after applying the direct distance constraint in our
      method. The twining and knotting of multiple threads correspond to stable
      solutions to contact and friction forces. A surgical suture scene is also modeled
      to demonstrate the practicality and simplicity of our method. CONCLUSIONS: Our
      method achieves stable and fast simulation of inextensible surgical thread.
      Benefiting from the unified particle framework, the rigid body, elastic rod, and
      soft body can be simultaneously simulated. The method is appropriate for
      applications in virtual surgery that require multiple dynamic bodies.

PMID- 29589261
TI  - Skeletal muscle overexpression of short isoform Sirt3 altered mitochondrial
      cardiolipin content and fatty acid composition.
AB  - Cardiolipin (CL) is a phospholipid at the heart of mitochondrial metabolism,
      which plays a key role in mitochondrial function and bioenergetics. Among
      mitochondrial activity regulators, SIRT3 plays a crucial role in controlling the
      acetylation status of many enzymes participating in the energy metabolism in
      particular concerning lipid metabolism and fatty acid oxidation. Data suggest
      that possible connection may exist between SIRT3 and CL status that has not been
      evaluated in skeletal muscle. In the present study, we have characterized
      skeletal muscle lipids as well as mitochondrial lipids composition in mice
      overexpressing long (SIRT3-M1) and short (SIRT3-M3) isoforms of SIRT3. Particular
      attention has been paid for CL. We reported no alteration in muscle lipids
      content and fatty acids composition between the two mice SIRT3 strains and the
      control mice. However, mitochondrial CL content was significantly decreased in
      SIRT3-M3 mice and associated to an upregulation of tafazzin gene expression. In
      addition, mitochondrial phospholipids and fatty acids composition was altered
      with an increase in the PC/PE ratio and arachidonic acid content and a reduction
      in the MUFA/SFA ratio. These modifications in mitochondrial membrane composition
      are associated with a reduction in the enzymatic activities of mitochondrial
      respiratory chain complexes I and IV. In spite of these mitochondrial enzymatic
      alterations, skeletal muscle mitochondrial respiration remained similar in SIRT3
      M3 and control mice. Surprisingly, none of those metabolic alterations were
      detected in mitochondria from SIRT3-M1 mice. In conclusion, our data indicate a
      specific action of the shorter SIRT3 isoform on lipid mitochondrial membrane
      biosynthesis and functioning.

PMID- 29589262
TI  - Ocimum basilicum but not Ocimum gratissimum present cytotoxic effects on human
      breast cancer cell line MCF-7, inducing apoptosis and triggering mTOR/Akt/p70S6K
      pathway.
AB  - Breast cancer is the major cause of death by cancer in women worldwide and in
      spite of the many drugs for its treatment, there is still the need for novel
      therapies for its control. Ocimum species have been used by traditional medicine
      to control several diseases, including cancer. We have previously characterized
      the antidiabetic properties of the unfractionated aqueous leaf extracts of Ocimum
      basilicum (OB) and Ocimum gratissimum (OG), modulating glucose metabolism in
      diabetic mice. Since glucose metabolism is primordial for cancer cells survival,
      we hypothesized that these extracts are effective against cancer cells. The
      unfractionated aqueous leaf extracts of OB and OG were chemically characterized
      and tested for their cytotoxic, cytostatic and anti-proliferative properties
      against the human breast cancer cell line MCF-7. Both extracts presented
      cytostatic effects with an 80% decrease in MCF-7 cell growth at 1 mg/mL. However,
      only OB promoted cytotoxic effects, interfering with the cell viability even
      after interruption of the treatment. Moreover, OB but not OG affected the cell
      proliferation and metabolism, evaluated in terms of lactate production and
      intracellular ATP content. After 24 h of treatment, OB treated cells presented an
      apoptotic profile, while OG treated cells were more necrotic. The treatment with
      both extracts also activated AMPK, but OB was much more efficient than OG in
      promoting this. The activation of mTOR signaling, another survival pathway was
      promoted by OB, whereas OG failed to activate it. In the end, we conclude that OB
      extract is efficient against the human breast cancer cell line.

PMID- 29589263
TI  - Combination of temperature shift and hydrolysate addition regulates anti-IgE
      monoclonal antibody charge heterogeneity in Chinese hamster ovary cell fed-batch
      culture.
AB  - Charge heterogeneity has been broadly studied as a critical quality attribute
      during monoclonal antibody (mAb) production that may subsequently affect product
      stability and biopotency. However, the charge variation distribution is poorly
      controlled, so methods of more effective control need to be explored. In this
      study, the combined effects of temperature shift (37-34, 37-32, or 37-30  degrees
      C) and hydrolysate addition (0.100 g/L) to culture feed on the charge
      heterogeneity of anti-IgE mAb were investigated. The results showed that the
      distribution of charge variation was significantly regulated by the combination
      of hydrolysate addition with a highly sub-physiological temperature (34  degrees
      C). In addition, under this condition, the main peak content significantly
      increased, and the acidic peak content significantly decreased. Furthermore, we
      explored Lys variant content, which is the major basic variant content, as well
      as its relationship with temperature shift and hydrolysate addition. Lys variant
      levels were positively related to the Lys and Arg concentrations in the medium
      and negatively related to carboxypeptidase B and carboxypeptidase H transcript
      levels. The combination of temperature shift and hydrolysate addition can thus
      effectively improve anti-IgE mAb charge heterogeneity and significantly increase
      main variant levels and decrease acidic variant levels.

PMID- 29589265
TI  - ESC position paper on cardiovascular toxicity of cancer treatments: challenges
      and expectations-comment.

PMID- 29589266
TI  - Efficient Culture of Intestinal Organoids with Blebbistatin.
AB  - The intestinal epithelium is one of the most rapidly self-renewing tissues
      throughout life in mammals. A small population of stem cells at the base of crypt
      in the epithelium can continually self-renew and give rise to differentiated
      epithelial cells. The self-renewal and differentiation of intestinal stem cells
      are under a tight control during homeostasis, and disruption of this balancing
      regulation leads to intestinal degeneration or tumorigenesis. Accordingly,
      exploration of the mechanism underlying the regulation of stem cells is essential
      for the understanding and treatment of intestinal disorders. As traditional
      methods using mice models are costly and time-consuming, the recently established
      ex vivo intestinal organoids model provides an ideal tool to investigate the
      mechanisms regulating the self-renewal and differentiation of intestinal stem
      cells. The intestinal organoids recapitulate major characteristics in both
      structure and function of intestinal epithelium in vivo. Here, we describe a new
      protocol to generate the intestinal organoids from both crypts and single stem
      cells with a higher efficiency using the small molecule blebbistatin and provide
      an approach to assess the self-renewal and differentiation of stem cells in
      intestinal organoids.

PMID- 29589264
TI  - Short- and Long-Term Oncological Outcome After Rectal Cancer Surgery: a
      Systematic Review and Meta-Analysis Comparing Open Versus Laparoscopic Rectal
      Cancer Surgery.
AB  - BACKGROUND: While several trials have compared laparoscopic to open surgery for
      colon cancer showing similar oncological results, oncological quality of
      laparoscopic versus open rectal resection is not well investigated. METHODS: A
      systematic literature search for randomized controlled trials was conducted in
      MEDLINE, the Cochrane Library, and Embase. Qualitative and quantitative meta
      analyses of short-term (rate of complete resections, number of harvested lymph
      nodes, circumferential resection margin positivity) and long-term (recurrence,
      disease-free and overall survival) oncologic results were conducted. RESULTS:
      Fourteen randomized controlled trials were identified including 3528 patients.
      Patients in the open resection group had significantly more complete resections
      (OR 0.70; 95% CI 0.51-0.97; p = 0.03) and a higher number of resected lymph nodes
      (mean difference - 0.92; 95% CI - 1.08 to 0.75; p < 0.001). No differences were
      detected in the frequency of positive circumferential resection margins (OR 0.82;
      95% CI 0.62-1.10; p = 0.18). Furthermore, no significant differences of long-term
      oncologic outcome parameters after 5 years including locoregional recurrence (OR
      0.95; 95% CI 0.44-2.05; p = 0.89), disease-free survival (OR 1.16; 95% CI 0.84
      1.58; p = 0.36), and overall survival (OR 1.04; 95% CI 0.76-1.41; p = 0.82) were
      found. Most trials exhibited a relevant risk of bias and several studies provided
      no information on the surgical expertise of the participating surgeons.
      CONCLUSION: Differences in oncologic outcome between laparoscopic and open rectal
      surgery for rectal cancer were detected for the complete resection rate and the
      number of resected lymph nodes in favor of the open approach. No statistically
      significant differences were found in oncologic long-term outcome parameters.

PMID- 29589267
TI  - Effect of Aluminum Exposure on Glucose Metabolism and Its Mechanism in Rats.
AB  - The effects of aluminum (Al) exposure on glucose metabolism and its mechanism
      were investigated. A total of 30 healthy Wistar male rats were randomly divided
      into two groups: control (GC) and experimental (GE). The GC group received
      intraperitoneal normal saline. The GE was established by intraperitoneal injected
      AlCl3 solution at 10 mg/kg for 30 days. Fasting blood glucose (FBG) and serum
      levels of insulin (FINS) were measured. The insulin resistance index (HOMA-IR)
      and pancreatic beta cell function index (HOMA-beta) were calculated and analyzed
      with homeostasis model assessment (HOMA). Pancreatic tissue was taken for
      pathological examination. Glucose transporter 4 (GLUT4) expression in skeletal
      muscle was detected by quantitative PCR and Western blot. Levels of FBG and HOMA
      IR in GE were higher than those in GC at day 10 and 20 (P < 0.05). FINS in GE
      were higher than those in GC at day 10 and 20, and lower than those in GC at day
      30 (P < 0.05). HOMA-beta in GE was lower than that of GC at every time point (P <
      0.05). Pathology showed that pancreatic damage changed more profoundly with
      prolongation of time in GE. Expression levels of GLUT4 mRNA and protein in rat
      skeletal muscle in GE were significantly lower than those in GC (P < 0.05). The
      results suggested that Al exposure affected glucose metabolism through pancreatic
      damage and reduction of GLUT4 expression.

PMID- 29589268
TI  - Changes in Trace Elements During Early Stages of Chronic Kidney Disease in Type 2
      Diabetic Patients.
AB  - Trace elements can influence glucose metabolism and be related to oxidative
      stress in type 2 diabetes mellitus. Moreover, trace elements play important roles
      in the nephrotic complications of these patients. Nevertheless, few
      investigations have been made into the changes in the levels of trace elements in
      diabetic patients at various stages of chronic kidney disease (CKD). The aims of
      this present study were to determine the levels of some important trace elements
      in diabetic patients during the early stages of CKD and to identify the
      relationship between these elements and CKD progression in type 2 diabetic
      patients. One hundred and forty-eight type 2 diabetic patients with chronic
      kidney diseases were recruited into this study. The subjects were grouped into
      four stages (1, 2, 3a, 3b) of CKD, according to their urine protein levels and
      estimated glomerular filtration rates (eGFRs). The levels of serum zinc and iron
      exhibited a statistically significant decreasing trend (P trend = 0.032 and
      0.047, respectively) from stage 1 to stage 3b after adjustment for age, gender,
      smoking, alcohol consumption, education, hypertension, and body mass index. The
      other tested elements, including copper, magnesium, selenium, chromium, and
      manganese, did not display any significant trends upon proceeding from stage 1 to
      stage 3b. Thus, serum zinc and iron appear to be useful markers when evaluating
      the early progression of CKD in type 2 diabetic patients.

PMID- 29589269
TI  - Reduced Myocardial Mitochondrial ROS Production in Mechanically Unloaded Hearts.
AB  - Mechanical ventricular unloading in advanced heart failure (HF) has been shown to
      induce reverse remodeling in myocardial tissues. Little is known about the impact
      of ventricular unloading on myocardial energy metabolism. We hypothesized that
      left ventricular unloading reduces myocardial mitochondrial reactive oxygen
      species (ROS) production and improves mitochondrial coupling efficiency in
      patients suffering from advanced HF. Left ventricular tissue specimens were
      harvested from explanted hearts at the time of transplantation. We compared
      myocardial metabolism in explanted hearts supported with an unloading ventricular
      assist device prior to transplantation (LVAD-HTX; n = 9) with tissue specimens of
      unsupported failing hearts (HTX; n = 6). Myocardial mitochondrial ROS production
      was decreased by 40% in LVAD-HTX compared to HTX patients (1.5 +/- 0.3 vs. 0.9 +/
      0.1 pmol/(s/mg); p < 0.05). High-resolution respirometry revealed increased
      mitochondrial coupling efficiency in LVAD-HTX patients (respiratory/control ratio
      1.7 +/- 0.2 vs. 1.2 +/- 0.2; p < 0.05). In conclusion, ventricular unloading is
      related to decreased mitochondrial ROS production and increased coupling
      efficiency in myocardium of human failing hearts, suggesting a novel
      pathomechanism of unloading-associated cardioprotection.

PMID- 29589271
TI  - Towards a Treatment for Intolerance of Uncertainty for Autistic Adults: A Single
      Case Experimental Design Study.
AB  - Intolerance of uncertainty (IU) is indicated as an important transdiagnostic
      process variable in a range of anxiety disorders. Anxiety is very common in
      autistic adults. This study evaluates a manualised treatment programme for
      autistic adults, which focused on IU. An eight session programme (CUES-A(c)) was
      developed and delivered to four autistic adults on an individual basis. A single
      case experimental design was used to provide a preliminary evaluation of the
      feasibility, acceptability and preliminary effectiveness of the programme. Data
      regarding retention, acceptability and feasibility indicate that the participants
      valued the programme. Analyses of outcome measures indicate that the programme
      has promise as a treatment option for autistic adults experiencing IU.

PMID- 29589272
TI  - Embedding Autism Spectrum Disorder Diagnosis Within the Medical Home: Decreasing
      Wait Times Through Streamlined Assessment.
AB  - Long waits for diagnostic assessment prevent early identification of children
      suspected of having autism spectrum disorder. We evaluated the benefit of
      embedded diagnostic consultation within primary care clinics. Using a streamlined
      diagnostic model, 119 children with concerns for autism spectrum disorder were
      seen over 14 months. Diagnostic clarity was determined through streamlined
      assessment for 59% of the children, while others required follow-up. Latency from
      first concern to diagnosis was 55 days and median age at diagnosis was 32 months:
      considerably lower than national averages or comparable tertiary clinics.
      Findings support that embedded processes for effective triage and diagnosis
      within the medical home is a viable mechanism for efficient access to diagnostic
      services and assists in bypassing a common barrier to specialized services.

PMID- 29589273
TI  - Children with Autism Spectrum Disorder Prefer Looking at Repetitive Movements in
      a Preferential Looking Paradigm.
AB  - The present study aimed to investigate the visual preference for repetitive
      movements in children with autism spectrum disorder (ASD). Young children with
      ASD and typically-developing (TD) children were presented simultaneously with
      cartoons depicting repetitive and random movements respectively, while their eye
      movements were recorded. We found that: (1) the children with ASD spent more time
      fixating on the repetitive movements than the random movements, whereas the TD
      children showed no preference for either type of movements; (2) the children's
      preference for the repetitive movements was correlated with the parent reports of
      their repetitive behaviors. Our findings show a promise in using the preferential
      looking as a potential indicator for the repetitive behaviors and aiding early
      screening of ASD in future investigations.

PMID- 29589274
TI  - Additive Effect of Variably Penetrant 22q11.2 Duplication and Pathogenic
      Mutations in Autism Spectrum Disorder: To Which Extent Does the Tree Hide the
      Forest?
AB  - The 22q11.2 duplication is a variably penetrant copy number variant (CNV)
      associated with a broad spectrum of clinical manifestations including autism
      spectrum disorders (ASD), and epilepsy. Here, we report on pathogenic HUWE1 and
      KIF1A mutations in two severely affected ASD/ID participants carrying a 22q11.2
      duplication. Based on previous studies, this CNV was originally considered as
      disease-causing. Yet, owing to their clinical severity, the participants were
      further investigated by next generation sequencing and eventually found to carry
      pathogenic mutations in HUWE1 and KIF1A respectively. We suggest giving
      consideration to additive effect of 22q11.2 duplication and pathogenic mutations
      when clinical presentation is either unusually severe or associated with atypical
      features. Caution should be exercised when delivering genetic counseling for
      variably penetrant CNVs, as uncertain penetrance of this CNV may lead to ignore
      additive pathogenic mutations. Systematic panel or exome sequencing of known ASD
      genes should be recommended when counseling families of patients carrying
      variably penetrant CNV.

PMID- 29589275
TI  - Surprising origin of two carved bones donated to the Buchenwald Memorial Museum.
AB  - Unidentified bones were donated to the Buchenwald Memorial Museum in Weimar,
      Germany. The donor thought the bones may have belonged to internees of the
      concentration camp and had been decoratively carved by camp personnel. Non
      destructive forensic anthropological examination was carried out on the bones to
      identify their possible origin. Comparative human and non-human bones samples
      were used to determine the provenance of the bones and the anatomical region they
      may have come from. Literature and internet searches were conducted to trace the
      origin of the carved motifs on the bones. The bones were determined to belong to
      the lower limb region of bovids. The carvings were found to correspond with those
      of existing bone examples found in some museums in the UK. They were traced to
      German prisoners of war dating to the First World War. An in-depth examination of
      the donated bones revealed their non-human provenance. It further showed that no
      link existed between the bones, internees of the concentration camp, and the time
      of the camp's existence. It was discovered that they belonged to the period 1914
      1918 and form an important part of German prisoner of war history in the UK.

PMID- 29589277
TI  - Effects of Microencapsulated Saccharomyces cerevisiae on Growth, Hematological
      Indices, Blood Chemical, and Immune Parameters and Intestinal Morphology in
      Striped Catfish, Pangasianodon hypophthalmus.
AB  - This study investigated the effects of dietary probiotic Saccharomyces cerevisiae
      in the striped catfish, Pangasianodon hypophthalmus, which is an important
      aquaculture species. Freeze-dried microencapsulated probiotic S. cerevisiae with
      guar gum was performed and used for fish feed supplementation. Striped catfish
      were fed for 120 days with one of three experimental diets: basal diet (control),
      basal diet supplemented with 106-CFU S. cerevisiae g-1 diet (S. cerevisiae 106),
      and basal diet supplemented with 108-CFU S. cerevisiae g-1 diet (S. cerevisiae
      108). The S. cerevisiae-supplemented diets significantly improved growth
      performance including growth rate and feed conversion ratio over 120 days of
      culture period (P < 0.05). The rate of survival was similar in all experimental
      groups. Supplementation with S. cerevisiae did not significantly affect whole
      body proximate composition (P > 0.05). In addition, probiotic S. cerevisiae had
      no effects on hematological indices and blood chemistry values (glucose,
      cholesterol, triglycerides, protein, albumin, blood urea nitrogen, chloride,
      calcium, magnesium, iron, and phosphorus) (P > 0.05). However, dietary S.
      cerevisiae led to increases in humoral immune parameters including total
      immunoglobulin, lysozyme, and alternative complement activities (P < 0.05).
      Dietary S. cerevisiae led to increase intestinal villus height in the anterior
      part of intestine (P < 0.05). Taken together, while the dietary S. cerevisiae had
      no detectable effects on hematological indices and several metabolic indicators,
      significant beneficial probiotic effects were observed on rates of growth, feed
      conversion ratio, and immune parameters.

PMID- 29589276
TI  - Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate
      Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in
      Various Cultured Cell Lines.
AB  - Alzheimer's disease is a neurodegenerative disease that affects 44 million people
      worldwide, costing the world $605 billion to care for those affected not taking
      into account the physical and psychological costs for those who care for
      Alzheimer's patients. Dipentylammonium is a simple amine, which is structurally
      similar to a number of other identified sigma-1 receptor ligands with high
      affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and
      dodecylamine. This study investigates whether dipentylammonium is able to provide
      neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE
      084. Here we identify dipentylammonium as a sigma-1 receptor ligand with
      nanomolar affinity. We have found that micromolar concentrations of
      dipentylammonium protect from glutamate toxicity and prevent NFkappaB activation
      in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably
      expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from
      toxicity induced by 150 MUM dopamine, suggesting that dipentylammonium may be
      useful for the treatment of Parkinsonian symptoms in Alzheimer's patients which
      are often associated with a more rapid deterioration of cognitive and physical
      ability. Finally, we found that low micromolar concentrations of dipentylammonium
      could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite
      outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a
      potential use in the treatment of neurodegenerative diseases and could be acting
      through the sigma-1 receptor.

PMID- 29589278
TI  - Frailty in Patients With Cirrhosis.
AB  - PURPOSE OF REVIEW: This review gives an overview of the evolving concept of
      physical frailty in patients with cirrhosis. As well as summarizing the available
      metrics that have been used to diagnose it, this review also examines the major
      recent trials that have investigated frailty in patients with cirrhosis. The
      complex relationship between sarcopenia and frailty is explored, and strategies
      to optimize frailty, such as including pharmacological and non-pharmacological
      therapies, are discussed. RECENT FINDINGS: Though there is heterogeneity between
      studies on how physical frailty in cirrhosis has been assessed, it is nonetheless
      becoming increasingly apparent that frailty in cirrhosis contributes to poor
      outcomes. A growing body of evidence strongly supports that frailty, as an entity
      distinct from comorbidity or measurable by laboratory-based liver disease
      severity, contributes to pre-transplant mortality and unplanned hospital
      admissions. If taken into account, frailty may improve pre-transplant mortality
      risk prediction. Physical frailty in cirrhosis may be objectively assessed by a
      number of validated metrics though at present, we lack a uniform consensus on the
      most appropriate tool. Early identification of frailty may allow optimization of
      the patient with the potential to avoiding adverse outcomes. Further studies are
      awaited validating and exploring optimal approaches to diagnosing and reversing
      frailty.

PMID- 29589279
TI  - Synthesis of Lactosucrose Using a Recombinant Levansucrase from Brenneria
      goodwinii.
AB  - Lactosucrose is a kind of trisaccharide that functions as a significant prebiotic
      in the maintenance of gastrointestinal homeostasis for human. In this study, a
      levansucrase from Brenneria goodwinii was further used for the lactosucrose
      production. The recombinant levansucrase showed efficiency in the lactosucrose
      production by transfructosylation from sucrose and lactose, and no other
      oligosaccharide or polysaccharide was detected in the reaction mixture. The
      transfructosylation product by this recombinant enzyme was structurally
      determined to be lactosucrose by FT-IR and NMR. The production condition was
      optimized as pH at 6.0, temperature at 35  degrees C, 5 U mL-1 enzyme, 180 g L-1
      sucrose, and 180 g L-1 lactose. Under the optimal condition, the enzyme could
      approximately produce 100 g L-1 lactosucrose when the reaction reached
      equilibrium. The recombinant levansucrase could effectively and exclusively
      catalyze the formation of lactosucrose, which might expand the enzymatic choice
      for further preparation of lactosucrose.

PMID- 29589280
TI  - Response to cyclosporine A and corticosteroids in adult patients with acquired
      pure red cell aplasia: serial experience at a single center.
AB  - To assess response to cyclosporine A, and/or corticosteroids, and possible
      factors influencing the response in adult patients with acquired pure red cell
      aplasia (PRCA). Clinical data from 42 cases were retrospectively analyzed. These
      patients received cyclosporine A (CsA), and/or corticosteroids (CS), or other
      immunosuppressive agents on becoming refractory and relapse. Thirty-nine patients
      were evaluated. Remission induction therapy included CsA (n = 16), CS (n = 13),
      CsA in combination with CS (n = 6), or other immunosuppressive agents (n = 4).
      Initial response rates were 75.0, 46.2, 66.7 and 75.0%, respectively (P = 0.456).
      Cumulative response rates in patients who received CsA, CS, CsA in combination
      with CS, or other immunosuppressive agents were 69.6% (16/23), 50.0% (7/14),
      71.4% (5/7), 42.9% (6/14), respectively (P = 0.376). Cumulative rates of CR were
      26.1% (6/23), 28.6% (4/14), 57.1% (4/7), 14.3% (2/14), respectively (P = 0.284).
      In 27 refractory and relapsed PRCA patients, 11 of 17 patients (64.7%) achieved
      remission by CsA and/or CS regimen, while three of ten patients (30.0%) responded
      to other immunosuppressive agents (P = 0.120). CsA and/or CS were effective in
      treating PRCA. For patients with relapse or refractory PRCA, there were no
      satisfactory treatments if CsA and/or CS failed or were not administered.

PMID- 29589282
TI  - Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted
      Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron
      Migration.
AB  - Mating behavior in males and females is dependent on olfactory cues processed
      through both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO).
      Signaling through the MOE is critical for the initiation of male mating behavior,
      and the loss of MOE signaling severely compromises this comportment. Here, we
      demonstrate that dosage of the homeodomain gene Six3 affects the degree of
      development of MOE but not the VNO. Anomalous MOE development in Six3
      heterozygote mice leads to hyposmia, specifically disrupting male mounting
      behavior by impairing detection of volatile female estrus pheromones. Six3 is
      highly expressed in the MOE, main olfactory bulb (MOB), and hypothalamus; all
      regions essential in the proper migration of the gonadotropin-releasing hormone
      (GnRH) neurons, a key reproductive neuronal population that migrates along
      olfactory axons from the developing nose into the brain. Interestingly, we find
      that the reduction in Six3 expression in Six3 heterozygote mice compromises
      development of the MOE and MOB, resulting in mis-migration of GnRH neurons due to
      improper olfactory axon targeting. This reduction in the hypothalamic GnRH neuron
      population, by 45% in adulthood, leads to female subfertility, but does not
      impact male hormone levels, suggesting that male infertility is not related to
      GnRH neuron numbers, but exclusively linked to abnormal olfaction. We here
      determine that Six3 is haploinsufficient for MOE development, GnRH neuron
      migration, and fertility, and represents a novel candidate gene for Kallmann
      syndrome, a form of inherited infertility.

PMID- 29589283
TI  - Detecting Alpha Synuclein Seeding Activity in Formaldehyde-Fixed MSA Patient
      Tissue by PMCA.
AB  - Alpha synuclein (alpha-syn) is central to the pathogenesis of a group of
      neurodegenerative disorders known as synucleinopathies, including Parkinson's
      disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
      Aggregation of alpha-syn is the pathologic hallmark of these disorders and is
      intimately associated with the pathogenic changes. The prion-like hypothesis
      postulates that the aggregated alpha-syn provides a template to seed the
      aggregation of normal alpha-syn and spread the pathology. Thus far, it remains
      unclear whether aggregated alpha-syn can be a useful biomarker for diagnosis
      and/or tracking disease progression, which is mainly due to the lack of a
      suitable biochemical assay. The protein misfolding cyclic amplification (PMCA)
      technique is known for its enormous amplification power to detect the seeding
      activity of protein aggregates such as prions. In this study, we adapted PMCA for
      detecting the seeding activity of alpha-syn. By extensively optimizing the PMCA
      parameters, we developed a protocol that is able to sensitively and
      quantitatively detect the seeding activity of as little as 100 attomoles (10-16
      mol) of alpha-syn aggregate. Using our protocol, we detected alpha-syn seeding
      activity from a histologically positive, formaldehyde-fixed MSA sample, but not
      with the histologically negative, formaldehyde-fixed control sample. Our results
      confirmed that the alpha-syn in MSA patient's brain does contain seeding
      activity, which remains active even after fixation. Moreover, we also established
      that PMCA with sonication is a sensitive and quantitative method for detecting
      alpha-syn seeding activity, which can be further adapted to more accessible
      patients' samples to evaluate alpha-syn aggregates as a biomarker for
      synucleinopathies.

PMID- 29589281
TI  - Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo
      Children's Cancer Study Group (TCCSG) Study L04-16.
AB  - The survival rate of children with acute lymphoblastic leukemia (ALL) has
      increased to approximately 90% after substantial progress in risk-oriented
      treatment strategies. Between 2005 and 2013, the Tokyo Children's Cancer Study
      Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The
      principal aim of this study was to assemble background characteristics and
      treatment outcomes, and gather genetic information on leukemic cells under
      central diagnosis. This report outlines the background characteristics and
      treatment outcomes of 1033 children with ALL treated according to a TCCSG
      platform. The 5-year event-free and overall survival (OS) rates for all children
      were 78.1 +/- 1.3 and 89.6 +/- 1.0%, respectively. The OS rate was significantly
      higher in children with B-cell precursor (BCP)-ALL (91.9 +/- 1.0%, n = 916) than
      in those with T-ALL (71.9 +/- 4.3%, n = 117, p < 0.001). In univariate analysis
      for BCP-ALL, children aged 1-6 years (5y-OS: 94.2 +/- 1.0%), with an initial
      white blood cell count of < 20,000/MUL (94.0 +/- 1.0%), high hyperdiploidy (95.4
      +/- 1.6%), ETV6-RUNX1 (97.4 +/- 1.2%) or TCF3-PBX1 (96.9 +/- 2.1%), and
      "Day8NoBlasts" (96.4 +/- 1.1%) had the best outcomes. Genetic investigation
      revealed two novel fusion genes within this cohort: ETV6-ZNF385A and ZNF362-TCF4.
      Our study highlighted the clinical aspects of genomic features of ALL in Japanese
      children. We provide fundamental information for the further molecular
      investigation of this disease.

PMID- 29589285
TI  - Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer.
AB  - BACKGROUND: Many studies showed an association between absolute neutrophil count
      (ANC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), monocyte
      lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with poor overall
      survival (OS) in patients with cancer. However, only a few studies were conducted
      to further investigate this association in colorectal cancer (CRC). METHODS:
      Clinical data from 299 stage IV CRC patients treated at King Hussein Cancer
      Center from 2004 to 2012 have been retrospectively reviewed. We examined the
      association between ANC, AMC, MLR, PLR, and NLR with lung metastasis in stage IV
      CRC. Receiver Operating Characteristic (ROC) curve analysis was operated to
      determine the optimal NLR cutoff value. Univariate and multivariate analysis were
      performed. RESULTS: The ROC value of 3.4 was determined as the cutoff value of
      NLR to study the association. Univariate and multivariate analysis showed that
      patients with high baseline NLR (>= 3.4) had more baseline lung metastasis than
      patients with low NLR (< 3.4) (p = 0.0001, p = 0.0151, respectively). Also,
      baseline NLR correlated significantly with the presence of lymphovascular
      invasion (p = 0.001). In patients with no baseline lung metastasis, high post
      treatment NLR was associated with consequent development of lung metastasis (p =
      0.0227). Other markers including ANC, AMC, MLR, and PLR were significantly
      associated with lung metastasis at time of diagnosis (p = 0.0006, p = 0.0006, p =
      0.0187, and p = 0.001, respectively). CONCLUSION: Results are suggesting that
      different hematologic markers obtained from a cheap test (CBC) could potentially
      be used to predict the likelihood of lung metastasis in stage IV CRC. Prospective
      studies are needed to further assess the immune cells' role in tumor metastasis
      promotion.

PMID- 29589286
TI  - Genetic and Environmental Contributions to Variation in the Posterior
      Communicating Collaterals of the Circle of Willis.
AB  - Variation in blood flow mediated by the posterior communicating collateral
      arteries (PComs) contributes to variation in the severity of tissue injury in
      obstructive disease. Evidence in animals and humans indicates that differences in
      the extent of PComs, i.e., their anatomic lumen diameter and whether they are
      present bilaterally, unilaterally, or absent, are a major factor. These
      differences arise during development since they are present at birth. However,
      the causal mechanisms are unknown. We used angiography after maximal dilation to
      examine involvement of genetic, environmental, and stochastic factors. The extent
      of PComs varied widely among seven genetically diverse strains of mice. Like pial
      collaterals in the microcirculation, aging and hypertension reduced PCom
      diameter, while in contrast, obesity, hyperlipidemia, metabolic syndrome, and
      diabetes mellitus had no effect. Naturally occurring intrauterine growth
      restriction had no effect on extent of PCom or pial collaterals in the adult. The
      number and diameter of PComs evidenced much larger apparent stochastic-dependent
      variation than pial collaterals. In addition, both PComs underwent flow-mediated
      outward remodeling after unilateral permanent MCA occlusion that varied with
      genetic background and was greater on the ipsilesional side. These findings
      indicate that variation in the number and diameter of PCom collateral arteries
      arises from stochastic factors and naturally occurring genetic variants that
      differ from those that cause variation in pial collateral arterioles.
      Environmental factors also contribute: aging and hypertension reduce PCom
      diameter. Our results suggest possible sources of variation of PComs in humans
      and provide information relevant when studying mouse models of occlusive
      cerebrovascular disease.

PMID- 29589284
TI  - Hypoxia-Induced Neuroinflammation and Learning-Memory Impairments in Adult
      Zebrafish Are Suppressed by Glucosamine.
AB  - This study investigated changes in neuroinflammation and cognitive function in
      adult zebrafish exposed to acute hypoxia and protective effects of glucosamine
      (GlcN) against hypoxia-induced brain damage. The survival rate of zebrafish
      following exposure to hypoxia was improved by GlcN pretreatment. Moreover,
      hypoxia-induced upregulation of neuroglobin, NOS2alpha, glial fibrillary acidic
      protein, and S100beta in zebrafish was suppressed by GlcN. Hypoxia stimulated
      cell proliferation in the telencephalic ventral domain and in cerebellum
      subregions. GlcN decreased the number of bromodeoxyuridine (BrdU)-positive cells
      in the telencephalon region, but not in cerebellum regions. Transient motor
      neuron defects, assessed by measuring the locomotor and exploratory activity of
      zebrafish exposed to hypoxia recovered quickly. GlcN did not affect hypoxia
      induced motor activity changes. In passive avoidance tests, hypoxia impaired
      learning and memory ability, deficits that were rescued by GlcN. A learning
      stimulus increased the nuclear translocation of phosphorylated cAMP response
      element binding protein (p-CREB), an effect that was greatly inhibited by
      hypoxia. GlcN restored nuclear p-CREB after a learning trial in hypoxia-exposed
      zebrafish. The neurotransmitters, gamma-aminobutyric acid and glutamate, were
      increased after hypoxia in the zebrafish brain, and GlcN further increased their
      levels. In contrast, acetylcholine levels were reduced by hypoxia and restored by
      GlcN. Acetylcholinesterase inhibitor physostigmine partially reversed the
      impaired learning and memory of hypoxic zebrafish. This study represents the
      first examination of the molecular mechanisms underlying hypoxia-induced memory
      and learning defects in a zebrafish model. Our results further suggest that GlcN
      associated hexosamine metabolic pathway could be an important therapeutic target
      for hypoxic brain damage.

PMID- 29589287
TI  - Waist circumference is a better predictor of risk for frailty than BMI in the
      community-dwelling elderly in Beijing.
AB  - AIM: Obesity is found to be associated with frailty. Body mass index (BMI) and
      waist circumference (WC) are the commonly used measures for obesity, the former
      is more closely related to general obesity and body weight; the latter can more
      accurately reflect abdominal obesity and is more closely associated with
      metabolic disorders. In this study, we intend to study the relationship between
      frailty, BMI and WC among older people. METHODS: Data were derived from the
      Beijing Longitudinal Study on Aging II Cohort, which included 6320 people 65
      years or older from three urban districts in Beijing. A Frailty Index derived
      from 33 items was developed according to Rockwood's cumulative deficits method. A
      Frailty Index >= 0.25 was used as the cut-off criteria. BMI was classified as
      underweight, normal, overweight, or obese (< 18.5, 18.5-< 24.0, 24.0-27.9, >=
      28.0 kg/m2, respectively). High WC was defined as WC >= 85 cm in men and >= 80 cm
      in women. RESULTS: People with a larger BMI (>= 28.0 kg/m2, 22.6%) or a larger WC
      (18.5%) were more likely to be frail. People with normal BMI and overweight
      people do not suffer from higher prevalence for frailty. In comparison with
      individuals with normal BMI (18.5-< 24.0 kg/m2) and normal WC (< 85 cm in men,
      <80 cm in women), the risk of frailty was higher among individuals who have
      normal BMI and large WC (odds ratio 1.68; 95% CI 1.33-2.12), have overweight and
      large WC (odds ratio 1.58; 95% CI 1.23-1.96), or have obesity and large WC (odds
      ratio 2.28; 95% CI 1.79-2.89). In people with normal WC, only those who are
      underweight have a higher risk for frailty (odds ratio 1.65, 95% CI 1.08-2.52).
      In comparison with BMI, the relation of WC with the risk for frailty was much
      closer. CONCLUSIONS: Abdominal obesity is more closely associated with incidence
      of frailty than general obesity in the elderly. Older adults with large waist
      circumference are more likely to be frail. Frailty in the elderly might be more
      closely related to metabolic disorders. WC might be a better measurement to
      detect frailty than BMI, given its relationship with metabolic disorders.

PMID- 29589288
TI  - Surgery or antibiotics for acute appendicitis? Take care about study's design and
      methodology!

PMID- 29589289
TI  - The relative merit of empirical priors in non-identifiable and sloppy models:
      Applications to models of learning and decision-making : Empirical priors.
AB  - Formal modeling approaches to cognition provide a principled characterization of
      observed responses in terms of a set of postulated processes, specifically in
      terms of parameters that modulate the latter. These model-based characterizations
      are useful to the extent that there is a clear, one-to-one mapping between
      parameters and model expectations (identifiability) and that parameters can be
      recovered from reasonably sized data using a typical experimental design
      (recoverability). These properties are sometimes not met for certain combinations
      of model classes and data. One suggestion to improve parameter identifiability
      and recoverability involves the use of "empirical priors", which constrain
      parameters according to a previously observed distribution of values. We assessed
      the efficacy of this proposal using a combination of real and artificial data.
      Our results showed that a point-estimate variant of the empirical-prior method
      could not improve parameter recovery systematically. We identified the source of
      poor parameter recovery in the low information content of the data. As a follow
      up step, we developed a fully Bayesian variant of the empirical-prior method and
      assessed its performance. We find that even such a method that takes the
      covariance structure of the parameter distributions into account cannot reliably
      improve parameter recovery. We conclude that researchers should invest additional
      efforts in improving the informativeness of their experimental designs, as many
      of the problems associated to impoverished designs cannot be alleviated by modern
      statistical methods alone.

PMID- 29589290
TI  - HTLV-1 proviral load in cerebrospinal fluid may not be a good marker to
      differentiate asymptomatic carriers with high proviral load in blood from HAM/TSP
      patients.
AB  - An elevated human T cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is an
      important risk factor for HTLV-1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP), although there is a considerable frequency of asymptomatic
      carriers (AC) with high PVL in blood. Our objective was to evaluate whether PVL
      quantified in cerebrospinal fluid (CSF) is helpful to distinguish AC from HAM
      when AC have high PVL in blood (ACH). ACH (n = 7) were characterized to have high
      PVL in blood by quantification of samples collected over time (mean 7 years). HAM
      patients (n = 14) also had analyzed blood samples collected at different times
      (mean 9 years). Comparing paired CSF and blood samples of each individual, CSF
      PVL mean was 4.7-fold higher than blood PVL in the ACH group and 10.8-fold in the
      HAM group. CSF PVL was significantly greater than blood PVL in the HAM group (p =
      0.004), but not in the ACH group. Important to highlight, CSF PVL was not
      significantly different between the ACH and the HAM groups. These results
      suggested that significantly higher PVL in CSF than in blood is a hallmark of
      HAM/TSP patients, but this is also true for asymptomatic carriers with high PVL
      in blood, thus reducing its usefulness as a marker for HAM/TSP. A greater number
      of ACH should be analyzed, but whether they will eventually develop HAM/TSP or
      why they have not developed the disease are still questions to be clarified.
      Longitudinal studies are necessary to answer these questions.

PMID- 29589291
TI  - Modelling Movement Energetics Using Global Positioning System Devices in Contact
      Team Sports: Limitations and Solutions.
AB  - Quantifying the training and competition loads of players in contact team sports
      can be performed in a variety of ways, including kinematic, perceptual, heart
      rate or biochemical monitoring methods. Whilst these approaches provide data
      relevant for team sports practitioners and athletes, their application to a
      contact team sport setting can sometimes be challenging or illogical.
      Furthermore, these methods can generate large fragmented datasets, do not provide
      a single global measure of training load and cannot adequately quantify all key
      elements of performance in contact team sports. A previous attempt to address
      these limitations via the estimation of metabolic energy demand (global energy
      measurement) has been criticised for its inability to fully quantify the
      energetic costs of team sports, particularly during collisions. This is despite
      the seemingly unintentional misapplication of the model's principles to settings
      outside of its intended use. There are other hindrances to the application of
      such models, which are discussed herein, such as the data-handling procedures of
      Global Position System manufacturers and the unrealistic expectations of end
      users. Nevertheless, we propose an alternative energetic approach, based on
      Global Positioning System-derived data, to improve the assessment of mechanical
      load in contact team sports. We present a framework for the estimation of
      mechanical work performed during locomotor and contact events with the capacity
      to globally quantify the work done during training and matches.

PMID- 29589293
TI  - The effect of day 2 versus day 3 embryo transfer on early pregnancy outcomes in
      women with a low yield of fertilized oocytes.
AB  - PURPOSE: To evaluate the differences in implantation and pregnancy rates when
      embryo transfer occurs on D2 versus D3 in women with a low yield of fertilized
      oocytes. METHODS: A total of 156 IVF/ICSI cycles from 141 women at an academic
      fertility center were analyzed in a retrospective fashion. Women with a low
      number of fertilized oocytes (<= 2 two pronuclei (2PN) stage zygotes) who had
      their fresh embryo transfer on D2 or D3 were included in the study. Positive
      pregnancy test per IVF cycle (PPT), clinical pregnancy rate (CPR), spontaneous
      abortion rate (SABR), and implantation rate (IMPR) were the main outcome measures
      assessed. Mann-Whitney U test and chi2 test were used as appropriate. A
      generalized linear mixed effect model adjusted for relevant covariates was
      conducted. P < 0.05 was considered significant. RESULTS: Patients having their
      embryo transfer on D2, when compared to those who had a D3 embryo transfer,
      experienced similar PPT [30.8 vs. 28.2%, respectively; adjusted OR (95%CI): 0.49
      (0.16, 1.52)], CPR [26.9 vs. 25.6%, respectively; adjusted OR (95%CI): 0.44
      (0.12, 1.67)], and IMPR [17.3 vs. 16.7%, respectively; adjusted beta (95%CI) -
      5.6% (- 15.0, 3.9)]. CONCLUSION: Our findings suggest that transferring embryos
      on D2 versus D3 in women with a limited number of 2PN stage zygotes does not
      affect early pregnancy outcomes. These results indicate that there can be some
      flexibility in scheduling the day of transfer at the convenience of both the
      patient and the center.

PMID- 29589294
TI  - Examination of the ovotoxicity of 5-fluorouracil in mice.
AB  - PURPOSE: Undesirable side effects of cancer treatments are common and include
      damage to the ovary, and depletion of the follicle reserve, which if severe
      enough, can lead to infertility and early menopause. Antimetabolite drugs, such
      as 5-fluorouracil (5-FU), are not considered to be detrimental to the ovary, but
      the ovotoxicity of 5-FU has not been evaluated in any detail. The purpose of this
      study was to evaluate the effects of 5-FU on follicle number. METHODS: In this
      study, adult female C57Bl6 mice (n = 4-6 animals/group) received a single dose of
      saline or 5-FU (150 mg/kg) and markers of ovarian damage and follicle depletion
      were assessed 12 h and 7 days later. RESULTS: Exposure to 5-FU did not alter
      primordial and primary follicle numbers. Atresia of secondary and antral
      follicles was increased significantly 12 h after 5-FU treatment, but atresia
      rates returned to levels similar to that of saline treated controls at 7 days.
      The number of corpora lutea were reduced 7 days after exposure to 5-FU, possibly
      as a consequence of earlier follicular atresia. CONCLUSIONS: These findings
      suggest that a single dose of 5-FU is mildly ovotoxic, but any effects on ovarian
      function are likely transient because the primordial follicle population is not
      depleted. Collectively, these data support the notion that 5-FU is unlikely to
      impact on the long-term fertility of women.

PMID- 29589292
TI  - Adherence to Antidepressants and Mortality in Elderly Patients with
      Cardiovascular Disease.
AB  - : BACKGROUND AND OBJECTIVE: Conflicting findings from studies evaluating the
      association between use of antidepressant drugs and mortality have been reported.
      We tested the hypothesis that better adherence to antidepressant therapy may
      reduce mortality. METHODS: The cohort included 29,845 individuals aged >= 65
      years from several Italian health units who were newly treated with
      antidepressant drugs after hospital discharge with a diagnosis for cardiovascular
      disease during 2008-2010. These individuals were observed from the first
      prescription until the end of data availability (i.e. 2012-2014, depending on the
      local database). During this period, information on (1) prescription of
      antidepressants and other medications and (2) death from any cause (outcome) was
      recorded. Proportional hazards models were fitted to estimate the association
      between better adherence to antidepressants (defined as proportion of days
      covered >= 75%) and outcome, by adjusting and stratifying for several covariates.
      RESULTS: Patients with better adherence to antidepressants had a reduced
      mortality of 9% (95% CI 3-14). Patients who did not use other medicaments during
      follow-up had reduced mortality associated with better adherence to
      antidepressants of 21% (- 1-38), 14% (7-20), 20% (13-26) and 13% (7-19) for no
      users of antihypertensive agents, lipid-lowering agents, other cardiovascular
      drugs and antidiabetics, respectively. CONCLUSIONS: Better adherence to
      antidepressants is associated with reduced all-cause mortality, mainly in
      patients who did not use other pharmacological treatments. Behavioural changes to
      enhance adherence among the elderly with cardiovascular disease might offer
      important benefits in reducing their mortality.

PMID- 29589295
TI  - The varicocele argument resurfaces.
AB  - A recent series of articles and reviews published in Fertility and Sterility have
      rekindled the more than half century debate on varicocelectomy. Every one of
      these articles favored strongly the repair of varicocele for male infertility.
      Since my review paper on this issue in 2001, published in Human Reproduction
      Update, and since advent of ICSI in 1993, I had thought that most reproductive
      physicians felt negatively about the benefit of varicocelectomy. However, more
      recent urological papers are causing this negative view to be re-evaluated. It is
      now advocated by some urologists that varicocelectomy improves sperm count and
      testosterone levels, and even improves the results with ICSI. Thus, it may be
      appropriate to revisit older studies again and review the newer ones in this
      never ending controversy. Newer studies are re-opening the door to review and
      possibly re-instate varicocelectomy. This dilemma may never be fully resolved,
      but it is important to keep an open mind.

PMID- 29589296
TI  - Understanding Treatment Effect Estimates When Treatment Effects Are Heterogeneous
      for More Than One Outcome.
AB  - BACKGROUND: Patient-centred care requires evidence of treatment effects across
      many outcomes. Outcomes can be beneficial (e.g. increased survival or cure rates)
      or detrimental (e.g. adverse events, pain associated with treatment, treatment
      costs, time required for treatment). Treatment effects may also be heterogeneous
      across outcomes and across patients. Randomized controlled trials are usually
      insufficient to supply evidence across outcomes. Observational data analysis is
      an alternative, with the caveat that the treatments observed are choices. Real
      world treatment choice often involves complex assessment of expected effects
      across the array of outcomes. Failure to account for this complexity when
      interpreting treatment effect estimates could lead to clinical and policy
      mistakes. OBJECTIVE: Our objective was to assess the properties of treatment
      effect estimates based on choice when treatments have heterogeneous effects on
      both beneficial and detrimental outcomes across patients. METHODS: Simulation
      methods were used to highlight the sensitivity of treatment effect estimates to
      the distributions of treatment effects across patients across outcomes. Scenarios
      with alternative correlations between benefit and detriment treatment effects
      across patients were used. Regression and instrumental variable estimators were
      applied to the simulated data for both outcomes. RESULTS: True treatment effect
      parameters are sensitive to the relationships of treatment effectiveness across
      outcomes in each study population. In each simulation scenario, treatment effect
      estimate interpretations for each outcome are aligned with results shown
      previously in single outcome models, but these estimates vary across simulated
      populations with the correlations of treatment effects across patients across
      outcomes. CONCLUSIONS: If estimator assumptions are valid, estimates across
      outcomes can be used to assess the optimality of treatment rates in a study
      population. However, because true treatment effect parameters are sensitive to
      correlations of treatment effects across outcomes, decision makers should be
      cautious about generalizing estimates to other populations.

PMID- 29589297
TI  - Clinical Impact of p27Kip1 and CaSR Expression on Primary Hyperparathyroidism.
AB  - We aimed to investigate the expressions of p27 kinase inhibitory protein 1
      (p27Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid
      tissue and to evaluate the relationship of these molecules with clinical and
      biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients
      with histopathologically confirmed parathyroid adenomas and 20 patients with
      normal parathyroid glands (which were removed incidentally during thyroid
      resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were
      performed in surgical specimens. Clinical features, biochemical parameters, and
      BMD measurements of patients with PHPT were evaluated retrospectively.
      Expressions of p27Kip1 and CaSR were decreased in parathyroid adenomas, compared
      to normal glands (p < 0.05). High intensity of CaSR staining (3+) was more
      frequent in normal parathyroid tissue (75%) than adenomas (12%) (p < 0.01).
      Hypertension was not observed in patients with high staining intensity of CaSR (p
      = 0.032). There was a negative association between CaSR expression and body mass
      index (BMI) (p = 0.027, r = - 0.313). There was no significant relationship
      between p27Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25
      hydroxy vitamin D levels, and bone density (p > 0.05). The expressions of p27Kip1
      and CaSR were decreased in PHPT patients. This reduction may play an important
      role in the pathogenesis of PHPT. However, neither p27Kip1 nor CaSR expression
      was found to be useful in predicting prognosis or severity of disease.

PMID- 29589298
TI  - Cell Line Models of Molecular Subtypes of Colorectal Cancer.
AB  - Colorectal cancer (CRC) is a genetically diverse disease necessitating the need
      for well-characterized and reproducible models to enable its accurate
      investigation. Recent genomic analyses have confirmed that CRC cell lines
      accurately retain the key genetic alterations and represent the major molecular
      subtypes of primary CRC, underscoring their value as powerful preclinical models.
      In this chapter we detail the important issues to consider when using CRC cell
      lines, the techniques used for their appropriate molecular classification, and
      the methods by which they are cultured in vitro and as subcutaneous xenografts in
      immune-compromised mice. A panel of commonly available CRC cell lines that have
      been characterized for key molecular subtypes is also provided as a resource for
      investigators to select appropriate models to address specific research
      questions.

PMID- 29589299
TI  - Dissecting Oncogenic RTK Pathways in Colorectal Cancer Initiation and
      Progression.
AB  - Colorectal cancer (CRC) is a progressive disorder associated with an accumulation
      of multiple heterogeneous genetic alterations in intestinal epithelial cells
      (IEC). However, when these cells undergo neoplastic transformation and become
      cancerous and metastatic, they invariably acquire hallmarks conferring them the
      ability to hyperproliferate, escape growth-inhibitory and death-inducing cues,
      and promote angiogenesis as well as epithelial-to-mesenchymal transformation
      (EMT), fostering their invasive dissemination from primary tumor into distant
      tissues. Compelling clinical and experimental evidence suggest that aberrant
      engagement of cell surface growth factor receptor tyrosine kinase (RTK)
      signaling, like that of the hepatocyte growth factor (HGF)/MET receptor,
      underlies CRC metastatic progression by promoting these cancer hallmarks. To
      date, though, the use of RTK-targeting agents has been viewed as a promising
      approach for the treatment of metastatic CRC, clinical success has been
      modest.Our vision is that the prospect of designing RTK-based, improved and
      innovative CRC therapies and prognostic markers likely rests on a comprehensive
      understanding of the biological processes and underlying regulatory molecular
      mechanisms by which deregulation of RTK signaling governs IEC's neoplastic
      transformation and their transition from noninvasive to metastatic and malignant
      cells. Herein, we describe our scheme for defining the full scope of oncogenic
      MET-driven cancer biological processes, in cellulo and in vivo, as well as the
      individual contribution of MET-binding effectors in a nontransformed IEC model,
      the IEC-6 cell line.

PMID- 29589300
TI  - Identification of Response Elements on Promoters Using Site-Directed Mutagenesis
      and Chromatin Immunoprecipitation.
AB  - Proximal promoters are located upstream of the transcription start sites of
      genes, and they contain regulatory sequences on which bind different
      transcription factors for promoting colorectal cancer progression. Here we
      describe the comprehensive methodology used previously for the identification and
      functional characterization of MYC-responsive elements in the integrin alpha1
      subunit (ITGA1) gene using a combination of in silico analysis, site-directed
      mutagenesis, and chromatin immunoprecipitation.

PMID- 29589301
TI  - Identification and Functional Analysis of Gene Regulatory Sequences Interacting
      with Colorectal Tumor Suppressors.
AB  - Several tumor suppressors possess gene regulatory activity. Here, we describe how
      promoter and promoter/enhancer reporter assays can be used to characterize a
      colorectal tumor suppressor proteins' gene regulatory activity of possible target
      genes. In the first part, a bioinformatic approach to identify relevant gene
      regulatory regions of potential target genes is presented. In the second part, it
      is demonstrated how to prepare and carry out the functional assay.We explain how
      to clone the bioinformatically identified gene regulatory regions into luciferase
      reporter plasmids by the use of the quick and efficient In-Fusion cloning method,
      and how to carry out transient transfections of Caco-2 colon cancer cells with
      the produced luciferase reporter plasmids using polyethyleneimine (PEI). A plan
      describing how to set up and carry out the luciferase expression assay is
      presented. The luciferase/beta-galactosidase (Dual Light) assay presented is a
      highly sensitive assay that can monitor small changes in the promoter/enhancer
      activity and includes an internal control monitoring transfection efficiency.

PMID- 29589302
TI  - Methods for In Vivo Functional Studies of Chromatin-Modifying Enzymes in Early
      Steps of Colon Carcinogenesis.
AB  - Since chromatin-modifying enzymes are involved in most processes needing to
      access the DNA fiber such as transcription, replication or DNA repair, their
      involvement in the regulation of gene expression in numerous physiopathological
      contexts is widely studied. Most of these enzymes are essential for cell growth
      and survival due to their pleiotropic roles and studying their impact in vivo on
      organ development or tissue physiopathology is challenging. In this chapter, we
      describe a chemically-mediated method to induce colorectal carcinogenesis that we
      have used to identify in vivo the role of two chromatin modifying enzymes
      belonging to the same multimolecular complex, the histone acetyltransferase Tip60
      and the histone variant-incorporating ATPase p400.

PMID- 29589304
TI  - Methods for Assessing Apoptosis and Anoikis in Normal Intestine/Colon and
      Colorectal Cancer.
AB  - Caspase-dependent apoptosis, including its distinct cell death subroutine known
      as anoikis, perform essential roles during organogenesis, as well as in the
      maintenance and repair of tissues. To this effect, the continuous renewal of the
      human intestinal/colon epithelium is characterized by the exfoliation by anoikis
      of differentiated cells, whereas immature/undifferentiated cells may occasionally
      undergo apoptosis in order to evacuate daughter cells that are damaged or
      defective. Dysregulated epithelial apoptosis is a significant component of
      inflammatory bowel diseases. Conversely, the acquisition of a resistance to
      apoptosis represents one of the hallmarks of cancer initiation and progression,
      including for colorectal cancer (CRC). Furthermore, the emergence of anoikis
      resistance constitutes a critical step in cancer progression (including CRC), as
      well as a limiting one that enables invasion and metastasis.Considering the
      implications of apoptosis/anoikis dysregulation in gut physiopathology, it
      therefore becomes incumbent to understand the functional determinants that
      underlie such dysregulation-all the while having to monitor, assess, or evidence
      apoptosis and/or anoikis. In this chapter, methodologies that are typically used
      to assess caspase-dependent apoptosis and anoikis in intestinal/colonic normal
      and CRC cells, whether in vivo, ex vivo, or in cellulo, are provided.

PMID- 29589303
TI  - The Colorectal Cancer Microenvironment: Strategies for Studying the Role of
      Cancer-Associated Fibroblasts.
AB  - Colorectal cancer (CRC) is a key public health concern and the second highest
      cause of cancer related death in Western society. A dynamic interaction exists
      between CRC cells and the surrounding tumor microenvironment, which can stimulate
      not only the development of CRC, but its progression and metastasis, as well as
      the development of resistance to therapy. In this chapter, we focus on the role
      of fibroblasts within the CRC tumor microenvironment and describe some of the key
      methods for their study, as well as the evaluation of dynamic interactions within
      this biological ecosystem.

PMID- 29589305
TI  - Molecular Analysis of the Microbiome in Colorectal Cancer.
AB  - The human gut microbiota plays a major role in the development of colorectal
      cancer (CRC). Many studies have attempted to define links between microbiota
      residents, their function and disease development. We now have incredible
      molecular tools to allow us to study the gut microbiome however in order to make
      best use of these sophisticated approaches we need to ensure that samples are
      collected and processed using standardized and reproducible protocols. Here we
      provide an overview of molecular analysis methods and describe protocols for
      collecting and processing clinical samples for subsequent microbiome analysis.

PMID- 29589306
TI  - Proteomics Analysis of Colorectal Cancer Cells.
AB  - Proteomics allows the simultaneous detection and identification of thousands of
      proteins within a sample. Here, we describe a quantitative method to compare
      protein expression and subcellular localization of different cell lines
      representative of different stages of colorectal cancer using stable isotope
      labeling with amino acids in culture, or SILAC. We also describe a biochemical
      fractionation approach to separate different cellular compartments and the
      necessary steps to obtain a specific proteomic profile of each cell line. This
      technique enables a comprehensive proteomic analysis of cancer cell lines and the
      identification of pathways that are deregulated in different cancer cell lines.

PMID- 29589307
TI  - Autophagic Flux Assessment in Colorectal Cancer Cells.
AB  - Autophagy protects colorectal cancer cells against therapeutic intervention.
      Autophagy is a continuous process, and autophagic flux requires both
      autophagosome synthesis and their subsequent degradation at lysosomes. Hence,
      cells with elevated autophagic flux display both rapid autophagosome generation
      and degradation. Here, we describe an immunoblot protocol coupled to
      pharmaceutical inhibition of autophagosome clearance to monitor autophagic flux
      levels between colorectal cancer cell lines.

PMID- 29589308
TI  - Classification of Colorectal Cancer in Molecular Subtypes by
      Immunohistochemistry.
AB  - Colorectal cancer (CRC) is a heterogeneous disease, which can be categorized into
      distinct consensus molecular subtypes (CMSs). These subtypes differ in both
      clinical as well as biological properties. The gold-standard classification
      strategy relies on genome-wide expression data, which hampers widespread
      implementation. Here we describe an immunohistochemical (IHC) Mini Classifier, a
      practical tool that, in combination with microsatellite instability testing,
      delivers objective and accurate scoring to classify CRC patients into the main
      molecular disease subtypes. It is a robust immunohistochemical-based assay
      containing four specific stainings (FRMD6, ZEB1, HTR2B, and CDX2) in combination
      with cytokeratin. We also describe an online tool for classification of
      individual samples based on scoring parameters of these stainings.

PMID- 29589309
TI  - Stool DNA Integrity Method for Colorectal Cancer Detection.
AB  - Fluorescence long DNA (FL-DNA) is a non-invasive and simple-to-perform stool DNA
      test. This assay consists of a qualitative and quantitative real-time PCR (RT
      PCR) analysis. FL-DNA has great potential in colorectal cancer (CRC) lesions
      detection used alone or in combination with the standard CRC screening tool:
      immunochemical fecal occult blood test (iFOBT).

PMID- 29589310
TI  - RT-qPCR for Fecal Mature MicroRNA Quantification and Validation.
AB  - By routinely and systematically being able to perform quantitative stem-loop
      reverse transcriptase (RT) followed by TaqMan(r) minor-groove binding (MGB)
      probe, real-time quantitative PCR analysis on exfoliated enriched colonocytes in
      stool, using human (Homo sapiens, hsa) micro(mi)RNAs to monitor changes of their
      expression at various stages of colorectal (CRC) progression, this method allows
      for the reliable and quantitative diagnostic screening of colon cancer (CC).
      Although the expression of some miRNA genes tested in tissue shows less
      variability in normal or cancerous patients than in stool, the noninvasive stool
      by itself is well suited for CC screening. An miRNA approach using stool promises
      to offer more sensitivity and specificity than currently used genomic,
      methylomic, or proteomic methods for CC screening.To present an application of
      employing miRNAs as diagnostic markers for CC screening, we carried out global
      microarray expression studies on stool colonocytes isolated by paramagnetic
      beads, using Affymetrix GeneChip miRNA 3.0 Array, to select a panel of miRNAs for
      subsequent focused semiquantitative PCR analysis studies. We then conducted a
      stem-loop RT-TaqMan(r) MGB probes, followed by a modified real-time qPCR
      expression study on 20 selected miRNAs for subsequent validation of the extracted
      immunocaptured total small RNA isolated from stool colonocytes. Results showed 12
      miRNAs (miR-7, miR-17, miR-20a, miR-21, miR-92a, miR-96, miR-106a, miR-134, miR
      183, miR-196a, miR-199a-3p, and miR214) to have an increased expression in stool
      of CC patients, and that later TNM stages exhibited more increased expressions
      than adenomas, while 8 miRNAs (miR-9, miR-29b, miR-127-5p, miR-138, miR-143, miR
      146a, miR-222, and miR-938) showed decreased expressions in stool of CC patients,
      which becomes more pronounced as the cancer progresses from early to late TNM
      stages (0-IV).

PMID- 29589311
TI  - A Stool Multitarget mRNA Assay for the Detection of Colorectal Neoplasms.
AB  - Noninvasive screening methods for the detection of colorectal cancers (CRC) at
      curable stages rely on the identification of specific biomarkers. Our group has
      shown that mRNA stool assays represent a powerful and robust approach for the
      prediction of colorectal neoplasms. In this methodological chapter, we describe
      the procedures to isolate good quality stool RNA and the steps to evaluate the
      levels of specific host mRNA markers such as ITGA6, MYC, and GADD45B using TaqMan
      based quantitative and droplet digital PCR approaches.

PMID- 29589312
TI  - Colorectal Cancer Detection Using Targeted LC-MS Metabolic Profiling.
AB  - Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and
      causes of cancer death. While the mortality rates from CRC have steadily
      declined, 50,000 individuals in the USA (and many times this number worldwide)
      still succumb to this illness every year. Early detection of CRC is the most
      critical need for improving 5-year survival and cure rates. Currently available
      CRC diagnostic techniques often miss early stage disease such that only 40% of
      newly diagnosed CRC patients are treated for local disease, Therefore,
      development of new screening methods that are highly sensitive, specific,
      noninvasive and easily accessible are critically desired for the early diagnosis
      and significant reduction in death rate from CRC. In this chapter we describe a
      targeted LC-MS based metabolic profiling approach used for the discovery of CRC
      metabolite biomarker candidates, based on highly reproducible hydrophilic
      interaction liquid chromatography coupled to triple-quadrupole mass spectrometry
      (HILIC-LC-QQQ-MS). A partial least squares-discriminant analysis (PLS-DA) model
      was able to differentiate CRC patients from both healthy controls and polyp
      patients, as well as to distinguish CRC patients based on the cancer stage.

PMID- 29589313
TI  - Proteomic Profiling for Colorectal Cancer Biomarker Discovery.
AB  - Nowadays, the ideal biomarker for colorectal cancer (CRC) has not been found. Two
      dimensional electrophoresis (2-DE) and mass spectrometry (MS) are suitable
      techniques for searching new biomarkers. In this chapter, we describe methodology
      for biomarker discovery based on a proteomic approach. In addition, special
      attention is given to the sample preparation, including protein extraction,
      fractionation, and cleanup, as we consider this a critical step. Comparing the
      proteomic profile of tumor and mucosa, we identified the nucleoside diphosphate
      kinase A (NDKA) protein as a candidate biomarker for CRC. Finally, we validated
      NDKA with an ELISA kit using serum samples from individuals of a screening
      cohort. Our results suggest that serum NDKA is a potential biomarker for
      screening of CRC and premalignant advanced adenomas (AA).

PMID- 29589314
TI  - Tumor-Derived Microparticles to Monitor Colorectal Cancer Evolution.
AB  - Colorectal cancer is the most common gastrointestinal cancer and the second-most
      common cause of cancer-related death worldwide. Microparticles are small vesicles
      known to be implicated in tumor growth, the development of metastases, and cancer
      associated procoagulant activity. We have reported a specific hallmark of
      microparticles in colorectal and pancreatic cancers, the so-called
      "microparticulosome." We have also reported on variations in the
      microparticulosome in the case of the occurrence of a thromboembolic event. Here,
      we describe our flow cytometry-based methods for identifying and characterizing
      tumor-derived microparticles and thereby monitoring colorectal cancer evolution.

PMID- 29589315
TI  - Molecular Testing for the Treatment of Advanced Colorectal Cancer: An Overview.
AB  - Concurrent with an expansion in the number of agents available for the treatment
      of advanced CRC, there has been an increase in our understanding of selection
      biomarkers to optimize the management of patients with this disease. For CRC
      patients being considered for anti-EGFR therapy, expanded RAS testing is the
      standard of care to determine the subset of patients who can benefit from
      cetuximab or panitumumab in conjunction with chemotherapy. A small fraction of
      patients have HER2 amplification where emerging data suggest treatment with drugs
      targeting this alteration. Although advanced CRC patients who harbor the BRAF
      V600E mutation have a poorer prognosis, they are eligible for combinatorial
      therapy targeting EGFR/BRAF or BRAF/MEK within the MAP kinase signaling pathway.
      Once primarily thought to be a negative prognostic marker, BRAF V600E mutation is
      now considered as a positive predictive factor with an opportunity for clinical
      intervention. A growing body of evidence also supports MSI testing as clinical
      benefits with immune checkpoint blockade by cancer immunotherapy have been
      demonstrated in MSI-high patients whose tumors exhibit high mutational burden. It
      has been established that UGT1A1*28 polymorphism is associated with irinotecan
      toxicity, but this test is rarely performed as the management strategy has not
      been identified. No established predictive biomarker for anti-VEGF therapy has
      yet to be discovered.It is becoming increasingly apparent that our growing
      understanding of biomarkers is revolutionizing and improving our strategies in
      the treatment of advanced CRC. Traditional nonselective cytotoxic chemotherapy is
      gradually being augmented and even in some cases supplanted by selective targeted
      agents based on our increasing understanding of tumor signaling and mechanism at
      the molecular level. The prospect of personalized medicine in directing treatment
      approaches that are optimally beneficial for patients brings tremendous
      excitement to the growing field of cancer therapeutics. As discussed in this
      chapter, the concurrent development of molecular biomarkers with new treatment
      strategies holds great promise of precision medicine in improving outcomes for
      patients with advanced CRC.

PMID- 29589316
TI  - Testing Cell-Based Immunotherapy for Colorectal Cancer.
AB  - Cell-based immunotherapy for cancer is emerging as an attractive alternative to
      conventional small-molecule or antibody-based treatment. Due to the
      characteristics of cell-based therapy, validation of test materials before in
      vivo administration is required. Here we describe general validation steps for
      preclinical evaluation of cell-based immunotherapy. We also describe a xenograft
      model of human colorectal cancer. This model can be used for applied to
      preclinical evaluation of various cell-based therapy regimens for colorectal
      cancer treatment.

PMID- 29589317
TI  - Patient-Derived Xenograft Models of Colorectal Cancer: Procedures for Engraftment
      and Propagation.
AB  - Preclinical compounds tested in animal models often demonstrate limited efficacy
      when transitioned into patients. As a result, individuals are assigned to
      treatment regimens that may be ineffective at treating their disease. The
      development of more clinically relevant models, such as patient-derived
      xenografts (PDXs), will (1) more completely mimic the human condition and (2)
      more accurately predict tumor responses to previously untested therapeutics.PDX
      models are clinically relevant as tumor tissue is implanted directly from human
      donor to the mouse recipient. Therefore, these models prevent cell population
      selection, intentional or unintentional, as the human tissue adapts to an in
      vitro, two-dimensional environment prior to implantation into a three-dimensional
      in vivo murine host. Often, cell heterogeneity and tumor architecture can be
      maintained from human to the PDX model in the mouse. This protocol describes the
      engraftment and propagation processes for establishing colorectal (CRC) PDX
      models in mice, using tumor tissue from human subjects.

PMID- 29589318
TI  - Use of Organoids to Characterize Signaling Pathways in Cancer Initiation.
AB  - The development of intestinal organoid technology has greatly accelerated
      research in the field of colorectal cancer. Contrary to traditional cancer cell
      lines, organoids are composed of multiple cell types arranged in 3D structures
      highly reminiscent of their native tissues. Thus, organoids provide a near
      physiological and readily accessible model to study tissue morphogenesis, adult
      stem cell behavior and tumorigenesis. Here, we provide protocols for establishing
      intestinal organoid cultures from genetically modified mouse lines and describe
      methods to overexpress and knockout genes of interest using lentiviral-based
      approaches.

PMID- 29589319
TI  - Identification of Novel Molecules Targeting Cancer Stem Cells.
AB  - Multiple studies focused on tumor heterogeneity and cellular hierarchies have
      demonstrated the role of cancer stem cells (CSC) in tumor initiation and
      recurrence. Colorectal cancer is one of the leading causes of cancer-related
      death and is hierarchically organized, with the majority of tumor cells
      descending from a small population of colon cancer stem cells (CCSCs). Such a
      rare self-renewing population is marked by the acquisition of distinct chromatin
      regulation and transcriptional programs. Fundamental molecular deviations between
      CCSCs and bulk tumor cells as well as normal tissues represent a unique
      therapeutic access to develop novel, selective anticancer therapies.In this
      chapter, we describe a methodological pipeline to identify novel molecules to
      selectively target human CCSC. We present a point-by-point description of a
      typical phenotypic molecular screening experiment, aiming to identify selective
      modulators of human CCSCs vs. normal intestinal progenitor cells.

PMID- 29589320
TI  - Growing Wealth Gaps in Education.
AB  - Prior research on trends in educational inequality has focused chiefly on
      changing gaps in educational attainment by family income or parental occupation.
      In contrast, this contribution provides the first assessment of trends in
      educational attainment by family wealth and suggests that we should be at least
      as concerned about growing wealth gaps in education. Despite overall growth in
      educational attainment and some signs of decreasing wealth gaps in high school
      attainment and college access, I find a large and rapidly increasing wealth gap
      in college attainment between cohorts born in the 1970s and 1980s, respectively.
      This growing wealth gap in higher educational attainment co-occurred with a rise
      in inequality in children's wealth backgrounds, although the analyses also
      suggest that the latter does not fully account for the former. Nevertheless, the
      results reported here raise concerns about the distribution of educational
      opportunity among today's children who grow up in a context of particularly
      extreme wealth inequality.

PMID- 29589321
TI  - A History and Overview of the Behavioral Neuroscience of Learning and Memory.
AB  - Here, I provide a basic history of important milestones in the development of
      theories for how the brain accomplishes the phenomenon of learning and memory.
      Included are the ideas of Plato, Rene Descartes, Theodule Ribot, William James,
      Ivan Pavlov, John Watson, Karl Lashley, and others. The modern era of learning
      and memory research begins with the description of H.M. by Brenda Milner and the
      gradual discovery that the brain contains multiple learning and memory systems
      that are supported by anatomically discrete brain structures. Finally, a brief
      overview is provided for the chapters that are included in current topics in
      Behavioral Neuroscience-Learning and Memory.

PMID- 29589322
TI  - Current Topics Regarding the Function of the Medial Temporal Lobe Memory System.
AB  - The first clear insight that the medial temporal lobe of the human brain was in
      fact a system of anatomically connected structures that were organized into a
      memory system came in 1957 from the observations by Brenda Milner of the noted
      amnesic patient H.M. Subsequent work in humans, monkeys, and rodents has
      identified all of the components of the medial temporal lobe (MTL) that formed
      the memory system. Currently, work is ongoing to identify the specific
      contributions each structure in the medial temporal lobe makes towards the
      formation and storage of long-term declarative memory. The historical background
      of this work is described including what insights the study of noted neurologic
      patients H.M. and E.P. provided for understanding the function of the medial
      temporal lobe. The development of an animal model of medial temporal lobe
      function is described. Additionally, the insights that lead to the understanding
      that the brain contains multiple, anatomically discrete, memory systems are
      described. Finally, three current topics of debate are addressed: First, does the
      perirhinal cortex exclusively support memory, or does it support both memory and
      higher order visual perception? Second, is there an anatomical separation between
      recollection and familiarity? Third, is the organization of spatial memory
      different between humans and rats, or perhaps the difference is between the
      working memory capacities of the two species?

PMID- 29589323
TI  - Whole-tissue 3D imaging reveals intra-adipose sympathetic plasticity regulated by
      NGF-TrkA signal in cold-induced beiging.
AB  - Sympathetic arborizations act as the essential efferent signals in regulating the
      metabolism of peripheral organs including white adipose tissues (WAT). However,
      whether these local neural structures would be of plastic nature, and how such
      plasticity might participate in specific metabolic events of WAT, remains largely
      uncharacterized. In this study, we exploit the new volume fluorescence-imaging
      technique to observe the significant, and also reversible, plasticity of intra
      adipose sympathetic arborizations in mouse inguinal WAT in response to cold
      challenge. We demonstrate that this sympathetic plasticity depends on the cold
      elicited signal of nerve growth factor (NGF) and TrkA receptor. Blockage of NGF
      or TrkA signaling suppresses intra-adipose sympathetic plasticity, and moreover,
      the cold-induced beiging process of WAT. Furthermore, we show that NGF expression
      in WAT depends on the catecholamine signal in cold challenge. We therefore reveal
      the key physiological relevance, together with the regulatory mechanism, of intra
      adipose sympathetic plasticity in the WAT metabolism.

PMID- 29589324
TI  - Not which forceps, but whether forceps?

PMID- 29589325
TI  - In reply: Not which forceps, but whether forceps?

PMID- 29589326
TI  - Robust multi-label transfer feature learning for early diagnosis of Alzheimer's
      disease.
AB  - Transfer learning has been successfully used in the early diagnosis of
      Alzheimer's disease (AD). In these methods, data from one single or multiple
      related source domain(s) are employed to aid the learning task in the target
      domain. However, most of the existing methods utilize data from all source
      domains, ignoring the fact that unrelated source domains may degrade the learning
      performance. Also, previous studies assume that class labels for all subjects are
      reliable, without considering the ambiguity of class labels caused by slight
      differences between early AD patients and normal control subjects. To address
      these issues, we propose to transform the original binary class label of a
      particular subject into a multi-bit label coding vector with the aid of multiple
      source domains. We further develop a robust multi-label transfer feature learning
      (rMLTFL) model to simultaneously capture a common set of features from different
      domains (including the target domain and all source domains) and to identify the
      unrelated source domains. We evaluate our method on 406 subjects from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) database with baseline
      magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data. The
      experimental results show that the proposed rMLTFL method can effectively improve
      the performance of AD diagnosis, compared with several state-of-the-art methods.

PMID- 29589327
TI  - Response to "Letter to the Editor" by R. Dhar.

PMID- 29589329
TI  - Tactical Neurocritical Care.
AB  - Neurocritical care is usually practiced in the comfort of an intensive care unit
      within a tertiary care medical center. Physicians deployed to the frontline with
      the US military or allied military are required to use their critical care skills
      and their neurocritical skills in austere environments with limited resources.
      Due to these factors, tactical critical care and tactical neurocritical care
      differ significantly from traditional critical care. Operational constraints, the
      tactical environment, and resource availability dictate that tactical
      neurocritical care be practiced within a well-defined, mission-constrained
      framework. Although limited interventions can be performed in austere conditions,
      they can significantly impact patient outcome. This review focuses on the US Army
      approach to the patient requiring tactical neurocritical care specifically point
      of injury care and care during transportation to a higher level of care.

PMID- 29589328
TI  - Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive
      Intracerebral Hemorrhage with Intraventricular Hemorrhage.
AB  - BACKGROUND: Concomitant acute ischemic lesions are detected in up to a quarter of
      patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding
      pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not
      been investigated. METHODS: Retrospective study of all 500 patients enrolled in
      the CLEAR III randomized controlled trial of thrombolytic removal of obstructive
      IVH using external ventricular drainage. The primary outcome measure was
      radiologically confirmed ischemic lesions, as reported by the Safety Event
      Committee and confirmed by two neurologists. We assessed predictors of ischemic
      lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid
      hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded
      assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days.
      RESULTS: Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH.
      Independent risk factors associated with ischemic lesions in logistic regression
      models adjusted for confounders were higher IVH volume (p = 0.004) and persistent
      subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume
      >= 15 ml had five times the odds of concomitant ischemic lesions compared to IVH
      volume < 15 ml. Patients with ischemic lesions had significantly higher odds of
      death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients
      without concurrent ischemic lesions. CONCLUSIONS: Occurrence of ischemic lesions
      in the acute phase of IVH is not uncommon and is significantly associated with
      increased early and late mortality. Extra-parenchymal blood (larger IVH and
      visible subarachnoid hemorrhage) is a strong predictor for development of
      concomitant ischemic lesions after ICH.

PMID- 29589330
TI  - The Use of Continuous EEG Monitoring in Intensive Care Units in The Netherlands:
      A National Survey.
AB  - BACKGROUND: Currently, continuous electroencephalographic monitoring (cEEG) is
      the only available diagnostic tool for continuous monitoring of brain function in
      intensive care unit (ICU) patients. Yet, the exact relevance of routinely applied
      ICU cEEG remains unclear, and information on the implementation of cEEG,
      especially in Europe, is scarce. This study explores current practices of cEEG in
      adult Dutch ICU departments focusing on organizational and operational factors,
      development over time and factors perceived relevant for abstaining its use.
      METHODS: A national survey on cEEG in adults among the neurology and adult
      intensive care departments of all Dutch hospitals (n = 82) was performed.
      RESULTS: The overall institutional response rate was 78%. ICU cEEG is
      increasingly used in the Netherlands (in 37% of all hospitals in 2016 versus in
      21% in 2008). Currently in 88% of university, 55% of teaching and 14% of general
      hospitals use ICU cEEG. Reasons for not performing cEEG are diverse, including
      perceived non-feasibility and lack of data on the effect of cEEG use on patient
      outcome. Mostly, ICU cEEG is used for non-convulsive seizures or status
      epilepticus and prognostication. However, cEEG is never or rarely used for
      monitoring cerebral ischemia and raised intracranial pressure in traumatic brain
      injury. Review and reporting practices differ considerably between hospitals.
      Nearly all hospitals perform non-continuous review of cEEG traces. Methods for
      moving toward continuous review of cEEG traces are available but infrequently
      used in practice. CONCLUSIONS: cEEG is increasingly used in Dutch ICUs. However,
      cEEG practices vastly differ between hospitals. Future research should focus on
      uniform cEEG practices including unambiguous EEG interpretation to facilitate
      collaborative research on cEEG, aiming to provide improved standard patient care
      and robust data on the impact of cEEG use on patient outcome.

PMID- 29589332
TI  - The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading
      Conditions.
AB  - Embolus Analogues (EAs) can provide understanding of the mechanical
      characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were
      fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood).
      Histological staining confirmed that EA composition compared sufficiently with
      human samples reported in literature. EAs were mechanically described under seven
      testing conditions: tensile, compression, shear wave ultrasound elastography
      (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young
      modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50%
      strain). The compressive Young modulus increased with increasing thrombin
      concentration, which was in agreement with the SWE results. There was no
      significant difference in Young modulus throughout the clot (p < 0.05). The EAs
      displayed a non-linear response under parallel plate rheometry, creep and stress
      relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear
      Solid model were used to fit the non-linear stress-strain response and time
      dependent properties, respectively. This is the first study in which bovine EAs,
      with and without addition of thrombin, are histologically and mechanically
      described with corresponding proposed constitutive equations. The equations and
      experimental data determined can be applied for future numerical and experimental
      testing of mammalian EAs and cardiac source clots.

PMID- 29589331
TI  - Population Pharmacokinetic Analysis of Asunaprevir in Subjects with Hepatitis C
      Virus Infection.
AB  - INTRODUCTION: Asunaprevir (ASV) is a potent, pangenotypic, twice-daily hepatitis
      C virus (HCV) NS3 inhibitor indicated for the treatment of chronic HCV infection.
      METHODS: A population pharmacokinetic (PPK) model was developed using pooled ASV
      concentration data from 1239 HCV-infected subjects who received ASV either as
      part of the DUAL regimen with daclatasvir or as part of the QUAD regimen with
      daclatasvir and peg-interferon/ribavirin. RESULTS: A two-compartment model with
      first-order elimination from the central compartment, an induction effect on
      clearance, and an absorption model consisted of zero-order release followed by
      first-order absorption adequately described ASV PK after oral administration. A
      typical value for ASV clearance (CL/F) was 50.8 L/h, increasing by 43% after 2
      days to a CL/F of 72.5 L/h at steady-state, likely due to auto-induction of
      cytochrome P450 3A4 (CYP3A4). Factors indicative of hepatic function were
      identified as key influential covariates on ASV exposures. Subjects with
      cirrhosis had an 84% increase in ASV area under the concentration time curve
      (AUC) and subjects with baseline aspartate aminotransferase (AST) above 78 IU/L
      had a 58% increase in area under the concentration time curve (AUC). Asians
      subjects had a 46% higher steady-state AUC relative to White/Caucasian subjects.
      Other significant covariates were formulation, age, and gender. CONCLUSION: The
      current PPK model provided a parsimonious description of ASV concentration data
      in HCV-infected subjects. Key covariates identified in the model help explain the
      observed variability in ASV exposures and may guide clinical use of the drug.
      FUNDING: Bristol-Myers Squibb.

PMID- 29589333
TI  - Effect of response format on cognitive reflection: Validating a two- and four
      option multiple choice question version of the Cognitive Reflection Test.
AB  - The Cognitive Reflection Test, measuring intuition inhibition and cognitive
      reflection, has become extremely popular because it reliably predicts reasoning
      performance, decision-making, and beliefs. Across studies, the response format of
      CRT items sometimes differs, based on the assumed construct equivalence of tests
      with open-ended versus multiple-choice items (the equivalence hypothesis).
      Evidence and theoretical reasons, however, suggest that the cognitive processes
      measured by these response formats and their associated performances might differ
      (the nonequivalence hypothesis). We tested the two hypotheses experimentally by
      assessing the performance in tests with different response formats and by
      comparing their predictive and construct validity. In a between-subjects
      experiment (n = 452), participants answered stem-equivalent CRT items in an open
      ended, a two-option, or a four-option response format and then completed tasks on
      belief bias, denominator neglect, and paranormal beliefs (benchmark indicators of
      predictive validity), as well as on actively open-minded thinking and numeracy
      (benchmark indicators of construct validity). We found no significant differences
      between the three response formats in the numbers of correct responses, the
      numbers of intuitive responses (with the exception of the two-option version,
      which had a higher number than the other tests), and the correlational patterns
      of the indicators of predictive and construct validity. All three test versions
      were similarly reliable, but the multiple-choice formats were completed more
      quickly. We speculate that the specific nature of the CRT items helps build
      construct equivalence among the different response formats. We recommend using
      the validated multiple-choice version of the CRT presented here, particularly the
      four-option CRT, for practical and methodological reasons. Supplementary
      materials and data are available at https://osf.io/mzhyc/ .

PMID- 29589335
TI  - Matrix Metalloproteinase 8: Could it Benefit the CAR-T Cell Therapy of Solid
      Tumors?- a- Commentary on Therapeutic Potential.

PMID- 29589336
TI  - Acute hospital reconfiguration and self-harm presentations: a before-and-after
      study.
AB  - BACKGROUND: The evidence for improved patient outcomes following acute hospital
      reconfiguration is limited. AIMS: We assessed the impact of the reconfiguration
      of acute services within a hospital group in terms of the number and clinical
      management of self-harm presentations. METHODS: The study was conducted across
      the three Mid-Western regional hospitals in Ireland during 2004-2014.
      Reconfiguration in April 2009 involved two hospitals reducing the operation of
      their emergency departments (EDs) from 24 to 12 h. We used Poisson regression
      analysis of data from the National Self-Harm Registry Ireland to assess change in
      the hospital burden and clinical management of self-harm associated with the
      reconfiguration. RESULTS: We observed that the cumulative decrease in self-harm
      presentations at the two reconfigured hospitals was of a similar magnitude to the
      increase observed at the larger hospital. Despite this large increase in
      presentations, there was only a small increase in admissions. Reconfiguration of
      hospital services was also associated with changes in the provision of
      assessments for self-harm patients. CONCLUSIONS: There is evidence to suggest
      that acute hospital reconfiguration of hospital services impacts on patterns of
      patient flow. Findings have implications for those implementing reconfiguration
      of acute services.

PMID- 29589334
TI  - Toward Escherichia coli bacteria machine for water oxidation.
AB  - Nature uses a Mn oxide-based catalyst for water oxidation in plants, algae, and
      cyanobacteria. Mn oxides are among major candidates to be used as water-oxidizing
      catalysts. Herein, we used two straightforward and promising methods to form
      Escherichia coli bacteria/Mn oxide compounds. In one of the methods, the bacteria
      template was intact after the reaction. The catalysts were characterized by X-ray
      photoelectron spectroscopy, visible spectroscopy, scanning electron microscopy,
      high-resolution transmission electron microscopy, diffuse reflectance infrared
      Fourier transform spectroscopy, Raman spectroscopy, and X-ray diffraction
      spectrometry. Electrochemical properties of the catalysts were studied, and
      attributed redox potentials were assigned. The water oxidation of the compounds
      was examined under electrochemical condition. Linear sweep voltammetry showed
      that the onsets of water oxidation in our experimental condition for bacteria and
      Escherichia coli bacteria/Mn oxide were 1.68 and 1.56 V versus the normal
      hydrogen electrode (NHE), respectively. Thus, the presence of Mn oxide in the
      catalyst significantly decreased (~ 120 mV) the overpotential needed for water
      oxidation.

PMID- 29589337
TI  - Future career intentions of higher specialist trainees in general Paediatrics.
AB  - BACKGROUND: A survey of paediatric higher specialist trainees was carried out in
      2002 assessing career intentions and perception of training. Fourteen years
      later, with increased numbers of trainees and a national model of care and a
      tertiary paediatric hospital on the horizon, we re-evaluated the career
      intentions of the current trainee workforce. AIMS: To assess the career
      intentions of the current paediatric higher specialist trainees. METHODS: A 28
      item questionnaire was developed based on a previously validated instrument and
      distributed online using the Royal College of Physicians of Ireland trainee
      database. RESULTS: We distributed the questionnaire to 118 eligible trainees and
      received responses from 92 (78%). Seventy-nine (86%) respondents desire a
      consultant post in Ireland. Seventy-five (82%) indicated that their preferred
      consultant post location was in a tertiary paediatric centre. Sixty-two trainees
      (67%) intend to become subspecialists with 25 (27%) planning a career in general
      paediatrics. This contrasts with the 2002 survey when 76% wished to work in urban
      centres and 61% of trainees planned a career in general paediatrics. CONCLUSION:
      There appears to be a mismatch between the career goals of the future paediatric
      consultant workforce and the requirements for staffing paediatric units
      nationally. This has the potential to complicate the proposed expansion of
      general paediatricians in regional centres and result in a significant proportion
      of current trainees failing to secure a post in their desired location.

PMID- 29589338
TI  - Cardiovascular disease risk factor profile of male Gaelic Athletic Association
      sports referees.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the primary cause of morbidity and
      mortality in Ireland and worldwide. Male sporting referees registered with the
      Gaelic Athletic Association (G.A.A.) represent the Irish male population due to
      the wide range of ages and CVD risk factors. Although G.A.A. referees, a
      predominately male population, play a pivotal part in the success of the game,
      there is a paucity of epidemiological evidence relating to their CVD health
      status. AIMS: The purpose of this study was to assess the CVD risk factor profile
      of male G.A.A. referees in Ireland. METHODS: An observational, cross-sectional
      study design was used to assess the CVD risk factor profile of the participants.
      A cluster and convenience sample method was used to recruit participants aged >=
      18 years within the G.A.A. referee community throughout Ireland. CVD risk factor
      profiles were studied using questionnaires, blood pressure (BP) and
      anthropometric measurements. RESULTS: A total of 183 male G.A.A. referees were
      studied with a mean age of 39 years (+/- 6, p = 0.000) for inter-county and 47
      (+/- 11) for club referees. Of the total population studied, 49% had pre
      hypertension and 60% were overweight. CONCLUSIONS: The findings from this study
      demonstrate the presence of hypertension and negative lifestyle behaviours within
      this male population. This justifies the need to implement a policy on the pre
      participation screening and risk reduction of CVD for male G.A.A. referees in
      Ireland. This health promotion intervention would assist in reducing the CVD
      epidemic within this specific population.

PMID- 29589339
TI  - Connecting Through Technology: a Collaborative Psychiatry Trainee and Educator
      Online Platform.

PMID- 29589340
TI  - Influence of Nutritional Status on the Absorption of Polyphyllin I, an Anticancer
      Candidate from Paris polyphylla in Rats.
AB  - BACKGROUND AND OBJECTIVES: Protein-calorie malnutrition (PCM) is one of the most
      suffered complications in cancer patients. Polyphyllin I (PPI), a saponin
      isolated from rhizome of Paris polyphylla, is a potential candidate in cancer
      therapy. In this study, the influence of nutritional status on the absorption of
      PPI in rats was explored after oral administration. METHODS: PCM rats, namely mal
      nourished (MN) rats, were induced from well-nourished (WN) rats by caloric
      restriction protocol. Intestinal absorption of PPI in WN and MN rats was
      evaluated by pharmacokinetic and intestinal perfusion methods. The potential
      mechanisms between two groups were investigated on the basis of intestinal
      permeability, intestinal efflux and PPI's depletions in vivo. The intestinal
      permeability was analyzed by determining the concentration of paracellular marker
      transport in serum and the expression of junction proteins in intestine. The
      intestinal efflux was evaluated through comparing the protein level of P
      glycoprotein (P-gp) in intestine, and the depletions of PPI and/or generation of
      its metabolites in liver and intestines were analyzed by liquid chromatography
      triple quadrupole mass spectrometry (LC-MS/MS) method. RESULTS: Compared to WN
      rats, the oral systemic exposure of PPI was significantly increased in MN rats,
      evidenced by significant enhancement of maximum plasma concentration (Cmax) and
      area under the plasma concentration-time curve (AUC0-60h) by more than 2.51- and
      3.71-folds as well as terminal elimination half-life (t1/2) prolonged from to 7.3
      to 14.1 h. Further studies revealed that the potential mechanism might be
      associated with combined contribution of improved intestinal absorption and
      depressed deglycosylation of PPI in MN rats. Furthermore, enhanced intestinal
      absorption of PPI was benefited from increased intestinal permeability and
      decreased intestinal efflux in MN rats. Meanwhile, the former manifested as
      increased transport of paracellular marker and decreased junction proteins
      levels, while the later evidenced by reduced P-gp expression. CONCLUSIONS: The
      oral exposure of PPI was enhanced in MN rats, which suggested that nutritional
      status alters the absorption of PPI, and thus the dosage of PPI should be
      modified during the treatment of cancer patient with PCM.

PMID- 29589342
TI  - What's up in 2014 and a brief review on 2013.

PMID- 29589341
TI  - Solidification of Nanostructured Lipid Carriers Loaded Testosterone Undecanoate:
      In Vivo and In Vitro Study.
AB  - To enhance the bioavailability of testosterone undecanoate (TU) and overcome the
      current problem of soft capsules (Andriol Testocaps(r)), Nano-structured lipid
      carriers (NLC) for TU was developed. First, suspension of TU-loaded NLC (TU-NLC)
      was prepared by high pressure homogenization; then adsorbent or a protective
      agent beta-cyclodextrin was used to solidify the suspension through a vacuum
      system; finally, the solid powder of TU-loaded NLC (solid TU-NLC) was filled into
      hard capsules. The characteristics of solid TU-NLC, were investigated in vitro
      and vivo. The particle size of TU-NLC was about 273.3 nm, the potential was
      0.156+/-0.04. Transmission electron microscope (TEM) revealed that the NLC was
      spherical and uniform. Differential scanning calorimetry (DSC) suggested the drug
      had been encapsulated into NLC lipid matrix. The drug release proved that solid
      TU-NLC showed a higher dissolution in vitro. The CaCO-2 cell permeability showed
      that solid TU-NLC could enhance trans-membrane absorption of the TU. Moreover,
      the AUC of solid TU-NLC formulations (4304+/-550.50 MUg/L*min) was higher than
      commercial product Andriol Testocaps(r) (3075+/-372.50 MUg/L*min). In conclusion,
      solid TU-NLC could enhance the rate of dissolution, and had a relatively higher
      bioavailability than Andriol Testocaps(r) in vivo GRAPHICAL ABSTRACT: .

PMID- 29589343
TI  - Anticoagulation therapy in haemophilia.
AB  - Patients with haemophilia (PWH) are relatively protected from cardiovascular
      death. Recent insights have shown that this is not due to less formation of
      atherosclerosis than in non-haemophilic men, therefore protection from the final
      occlusive thrombus will be the major determinant. Prevalence and incidence rates
      of cardiovascular disease (especially non-fatal events) are scarce, although
      ongoing studies are addressing this issue.Meanwhile, because the haemophilia
      population is aging, we are increasingly confronted with cardiovascular events.
      The main cardio vascular risk factors that should be part of regular screening
      programs are hypertension, overweight, lipometabolic disorders and smoking.
      Anticoagulation therapy in haemophilia is feasible, provided that individual
      tailored coagulation therapy and close monitoring is provided.Here, we present
      our view on anticoagulation management in PWH. There is an absolute need for risk
      assessment tools and prospective validation of suggested anticoagulation
      management strategies in PWH. Until then, we are managing the unknown.

PMID- 29589344
TI  - Successful Surgical Removal of A Massive Iliopsoas Pseudotumor in a Boy With Mild
      Hemophilia A.

PMID- 29589345
TI  - Neonatal Listeriosis and The Importance of Body Surface Cultures.

PMID- 29589347
TI  - 59th Annual Congress of the Gesellschaft fur Thrombose- und Hamostaseforschung e.
      V.

PMID- 29589348
TI  - Platelet pathology and vascular medicine.

PMID- 29589346
TI  - [Recommendations for Diagnostics and Therapy of Children with Cancer Presenting
      with Fever and Neutropenia - Comparison of Two Current Guidelines].
AB  - Immunocompromised children and adolescents receiving treatment for cancer have a
      considerably increased risk for infection. Neutropenia is the most important
      single risk factor for infectious complications, and fever in neutropenia is
      considered as an emergency. Whereas guidelines for the management of fever in
      neutropenic adults have been established for decades, specific pediatric
      guidelines have not been developed until recently. As children differ in many
      aspects from adults such as in the underlying malignancy or in the availability
      and dosing of antimicrobial compounds, guidelines for pediatric patients are
      important. This article reviews similarities and differences between the recently
      published German interdisciplinary guideline of the German Societies of Pediatric
      Infectious Diseases and Pediatric Oncology and Hematology and a guideline
      developed by a panel of international experts for the management of fever in
      neutropenia in children and adolescents.

PMID- 29589349
TI  - The vulnerable myocardium.
AB  - Cardiovascular disease is the major cause of morbidity and mortality in subjects
      suffering from diabetes mellitus. While coronary artery disease is the leading
      cause of cardiac complications in diabetics, it is widely recognized that
      diabetes increases the risk for the development of heart failure independently of
      coronary heart disease and hypertension. This increased susceptibility of the
      diabetic heart to develop structural and functional impairment is termed diabetic
      cardiomyopathy. The number of different mechanisms proposed to contribute to
      diabetic cardiomyopathy is steadily increasing and underlines the complexity of
      this cardiac entity.In this review the mechanisms that account for the increased
      myocardial vulnerability in diabetic cardiomyopathy are discussed.

PMID- 29589350
TI  - The vulnerable blood.
AB  - Patients with diabetes are at increased risk of cardiovascular morbidity and
      mortality. While arteriosclerotic lesions have long been recognized as the
      underlying cause more recent studies suggest that alterations of the blood are
      also critically involved. Following plaque rupture, adherence of platelets is
      followed by the formation of a cross-linked fibrin clot. Patients with diabetes
      exhibit a prothrombotic milieu consisting of hyper reactive platelets, a tight
      and rigid clot structure which is due to up-regulation of coagulation factors and
      prolongation of clot lysis. Metabolic alterations as well as inflammatory
      processes, which are up-regulated in diabetes, are thought to be the main
      underlying causes. More recently, the complement cascade has emerged as a
      potential new player in this context with several complement components directly
      influencing both platelet function and coagulation.This review provides an
      overview concerning the changes that lead to alterations of platelet function and
      clot structure in diabetes.

PMID- 29589351
TI  - Genetics in thrombophilia.
AB  - Venous thromboembolism (VTE) poses a worldwide health burden affecting millions
      of people each year. The annual incidence of symptomatic VTE, the collective term
      used here for deep venous thrombosis, pulmonary embolism or both, is 2-3 per
      thousand inhabitants. The one-year mortality is 20% after a first VTE. Of the
      surviving patients 15-25% will experience a recurrent episode of VTE in the three
      years after the first event. Primary and secondary prevention is key to reducing
      death and disability from VTE. How to make use of our current knowledge of
      inherited risk of VTE for primary and secondary disease prevention is not
      straightforward. This despite the fact that in the past two or three decades we
      have made major strides in enlarging our understanding of inherited VTE risk, and
      that new inherited risk factors continue to be identified.For primary prevention
      of VTE genetic testing is not likely to play a role in the future. Genetic
      variations also determine recurrence risk, albeit that the effect sizes for
      individual genetic variations are invariably lower than those for first VTE
      events. Multilocus genetic risk scores improve risk classification, and it is now
      possible to stratify patients who have had a first venous thrombosis, into
      subgroups with a high and low risk of recurrence. Whether this approach can be
      used to tailor intensity and duration of treatment remains to be established.

PMID- 29589352
TI  - Kidney and haemostasis.
AB  - : Renal insufficiency is characterized by thrombocytopathy, caused by the
      accumulation of water soluble and protein bound waste products of protein
      metabolism, which are not adequately eliminated by the kidney. The kidneys also
      excrete drugs and their metabolites, which accumulate if dosages are not adjusted
      to the renal function and may cause clinically relevant bleeding (i. e. synthetic
      penicillins, vitamin K antagonists, new oral anticoagulants). Therefore, each
      patients kidney function (GFR) ought to be evaluated by the KDIGO guidelines. The
      survival of chronic renal patients is lowered by increasing cardiovascular
      complications. Particularly frequent is non-valvular atrial fibrillation. The
      recommended prophylaxis with vitamin K antagonists for renal insufficiency is
      hampered by increased bleeding as well as by augmented (coronary) vascular and
      valvular calcification. It is not known yet whether prophylaxis with vitamin K
      may prevent this complication. CONCLUSION: Because new oral anticoagulants are
      equally or even more effective and cause less bleeding, they may be favoured in
      future and even in end-stage renal failure if more is known about dosing, safety
      and efficacy. The measurement of serum FGF 23 concentration may be helpful as a
      marker for their use.

PMID- 29589353
TI  - Anticoagulation in patients with impaired renal function and with haemodialysis.
AB  - Patients with impaired renal function are exposed to an increased risk for
      bleeding complications depending on the amount of the anticoagulant eliminated by
      the kidneys. The elimination of unfractionated heparins, vitamin K antagonists
      and argatroban is only minimally influenced by a reduced renal function. Low
      molecular weight heparins, fondaparinux, danaparoid, hirudins and nonvitamin K
      antagonist oral anticoagulants (NOAC) cause a variably increased bleeding risk in
      renal impairment. Dose reductions are recommended for all of these anticoagulants
      in renal impairment, some are even contraindicated at certain levels of renal
      impairment. Their benefit over the conventional anticoagulants is preserved if
      renal dosing is employed. For end-stage renal disease patients specific treatment
      regimens are required.

PMID- 29589354
TI  - ?

PMID- 29589356
TI  - ?

PMID- 29589355
TI  - ?

PMID- 29589357
TI  - The protein Z/protein Z-dependent protease inhibitor complex.
AB  - Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984
      but it has no enzymatic activity. It is a cofactor of a serpin, the protein Z
      dependent protease inhibitor (ZPI), and the complex PZ/ZPI inhibits activated
      factor X on phospholipid surfaces. In mice, the disruption of PZ or ZPI gene is
      asymptomatic, but enhances the thrombotic phenotype and mortality of other
      thrombotic risk factors. Most of the clinical studies focused on PZ. Despite
      conflicting results, a recent meta-analysis indicated that PZ deficiency could be
      a risk for venous and arterial thrombosis and early fetal loss. However, these
      conclusions are drawn from case-control studies of small size, constituting an
      important limitation. Recently, it was shown that PZ and/or ZPI are synthesised
      by normal kidney and different cancer cells, suggesting that the complex PZ/ZPI
      could play a role in inhibiting the tissue deposition of fibrin. The
      physiopathological consequences of these observations remain to be established.
      At this time, the measurement of plasma PZ and ZPI or analysis of their gene
      polymorphisms should not be performed routinely for the exploration of
      thrombophilia.

PMID- 29589359
TI  - Impact-Faktor 2011 = 1,190.

PMID- 29589358
TI  - Factor VII activating protease.
AB  - Factor VII activating protease (FSAP) is a circulating serine protease with high
      homology to fibrinolytic enzymes. A role in the regulation of coagulation and
      fibrinolysis is suspected based on in vitro studies demonstrating activation of
      FVII or pro-urokinase plasminogen activator (uPA). However, considering the
      paucity of any studies in animal models or any correlative studies in humans the
      role of FSAP in haemostasis remains unclear. In relation to vascular remodeling
      processes or inflammation it has been convincingly shown that FSAP interacts with
      growth factors as well as protease activated receptors (PAR). Against this sparse
      background there are a plethora of studies which have investigated the linkage of
      single nucleotide polymorphisms (SNP) in the FSAP gene (HABP2) to various
      diseases. The G534E SNP of FSAP is associated with a low proteolytic activity due
      to an amino acid exchange in the protease domain. This and other SNPs have been
      linked to carotid stenosis, stroke as well as thrombosis in the elderly and
      plaque calcification. These SNP analyses indicate an important role for FSAP in
      the regulation of the haemostasis system as well as fibroproliferative
      inflammatory processes.

PMID- 29589360
TI  - ?

PMID- 29589361
TI  - Elinogrel, an orally and intravenously available ADP-receptor antagonist.
AB  - The antiplatelet therapy with aspirin and the ADP-receptor blocker clopidogrel is
      currently the standard medication after coronary intervention or after acute
      coronary syndrome to prevent recurrent ischemic events and reduce mortality.
      However, high interindividual response variability to antiplatelet treatment is
      described in up to 44% of treated patients. A poor response to clopidogrel is
      caused by multifactorial mechanisms. Individual risk assessment including
      platelet function testing (PFT) can help to identify high risk patients, although
      recent randomized trials to investigate effects of PFT-guided therapy have failed
      to detect an impact on prognostic outcome. Poor response to standard antiplatelet
      agents can be overcome by switching to alternate substances. Elinogrel is a novel
      competitive, reversible ADP-receptor antagonist available in oral and intravenous
      formulation. Additional treatment with elinogrel showed advantages over
      clopidogrel, including more rapid, less variable, and more complete inhibition of
      platelet function without significantly increased bleeding complications. This
      review gives an overview over the investigational drug elinogrel for use in a
      personalized antiplatelet approach.

PMID- 29589362
TI  - Oral anticoagulation with edoxaban.
AB  - Edoxaban (the former DU176b) an orally available direct factor Xa inhibitor has
      been engineered from DX-9065a, which was one of the first parenteral Xa
      inhibitors. Edoxaban has a time to peak plasma concentrations of 1-2 hours and a
      half-life of approximately 10 hours after multiple doses. Edoxaban is the third
      new oral anticoagulant in the group of direct factor Xa inhibitors that has
      gained clinical approval for the prevention of venous thromboembolism after major
      orthopaedic surgery. Currently, edoxaban is assessed in late stage clinical
      development for the prevention of stroke and systemic embolism in patients with
      non-valvular atrial fibrillation (ENGAGE AF-TIMI 48, NCT00781391) and for the
      treatment and prevention of venous thromboembolism in patients with acute deep
      vein thrombosis and/or pulmonary embolism (HOKUSAI VTE, NCT00986154).Both
      clinical phase III trials represent the largest single clinical studies in their
      entity so far with an enrolment of 21 107 patients in ENGAGE AF-TIMI 48 and a
      planned enrolment of 7500 patients in HOKUSAI VTE.The pharmacological properties
      of edoxaban will be discussed along with the current late stage clinical
      development focusing on the prevention of stroke and venous thromboembolism.

PMID- 29589363
TI  - Vorapaxar expands antiplatelet options.
AB  - Vorapaxar is the first substance of a new class of antiplatelet drugs that has
      been tested in large clinical trials. The protease-activated receptor 1 (PAR-1)
      antagonist inhibits thrombin-induced platelet activation to prevent
      atherothrombosis. In the phase 3 trials TRACER (acute coronary syndrome) and TRA
      2P-TIMI 50 (stable atherosclerosis) reducing ischemic events with vorapaxar came
      at the cost of bleeding.TRACER compared vorapaxar to placebo in 12 944 patients
      who had non-ST-segment elevation acute coronary syndromes on top of contemporary
      treatment including dual antiplatelet therapy (aspirin and clopidogrel).
      Vorapaxar reduced ischemic events non-significantly, but increased bleeding
      significantly, therefore not justifying triple antiplatelet therapy in this
      setting. Follow-up was stopped early because of bleeding. TRA 2P-TIMI 50 examined
      26 449 patients who had a history of myocardial infarction, ischemic stroke, or
      peripheral arterial disease. Vorapaxar reduced ischemic events and increased
      bleeding both significantly. Recruitment of patients with prior stroke was
      stopped early. Net clinical outcome and subgroup analyses suggested that
      vorapaxar could be beneficial for patients with prior myocardial infarction - but
      no history of stroke.

PMID- 29589364
TI  - Atopaxar.
AB  - Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor
      1 (PAR-1) thrombin receptor antagonist. To date, Atopaxar has been investigated
      in phase II trials with focus on safety and tolerability in patients with acute
      coronary syndromes or stable coronary artery disease on top of standard
      antiplatelet therapy. Atopaxar was generally well tolerated, however a rise in
      liver enzymes and prolongation of the QTcF interval were observed. The data
      suggest, that atopaxar administration may promote some minor bleeding
      complications, but does not seem to significantly increase the risk of major
      bleeding. Although not powered for efficacy, the currently available data suggest
      potential benefits in patients at high risk for recurrent ischemic events on top
      of standard antiplatelet therapy. In conclusion, more studies (e.g. phase III)
      are needed to evaluate efficacy and safety of atopaxar.

PMID- 29589370
TI  - Percutaneous mitral balloon valvuloplasty: beyond classic indications.
AB  - BACKGROUND AND AIM: In patients with mitral stenosis (MS) percutaneous mitral
      balloon valvuloplasty (PMBV) is used to im-prove symptoms and prognosis. Although
      there is some evidence for potential long-term benefits from PMBV in asymptomatic
      patients with mitral valve area (MVA) between 1.0 and 1.5 cm2, there are no
      follow-up data on patients with symptomatic MS with MVA > 1.5 cm2, who underwent
      PMBV. METHODS: We retrospectively analysed periprocedural results of 113
      symptomatic patients who underwent PMBV for MS with MVA > 1.5 cm2 (group 1) and
      compared them with a control group of patients with MVA <= 1.5 cm2 (group 2).
      Clinical and procedural variables were compared between groups. RESULTS: In group
      1, PMBV resulted in a significant increase of MVA as well as a decrease of mean
      and maximal mitral gradients and mean left atrial pressure (LAP), and a
      subsequent decrease of mean and systolic pulmonary artery pressures (PAPs).
      Moreover, 6.3% of patients developed moderate to severe (3+) or severe (4+) post
      procedural mitral regurgitation (MR). Post-procedural increase in MVA and
      decrease of LAP were more pronounced in group 2 than group 1 (?MVA 0.74 cm2 vs.
      0.41 cm2, p < 0.05, and ?LAP 8.2 mmHg vs. 6.0 mmHg, p < 0.05). Nonetheless, no
      significant differences were observed for ? of mean and systolic PAPs. The grade
      of post-procedural MR was comparable between groups. CONCLUSIONS: PMBV is a
      feasible procedure in highly selected patients without classic echocardiographic
      indications. None-theless, it is associated with a small but non-negligible
      periprocedural risk of developing severe MR.

PMID- 29589371
TI  - [2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial
      Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)]

PMID- 29589372
TI  - Fractional flow reserve and visual assessment for moderate coronary artery
      stenosis.

PMID- 29589373
TI  - Aortic root remodelling with aortic annuloplasty and aortic arch replacement one
      year after surgical treatment of acute aortic dissection.

PMID- 29589374
TI  - Successful primary intervention in a single coronary artery.

PMID- 29589375
TI  - Implantable cardioverter-defibrillator in a patient with left ventricular non
      compaction cardiomyopathy.

PMID- 29589376
TI  - Hybrid ablation of haemodynamically unstable ventricular tachycardia using a
      transabdominal minimally-invasive approach and percutaneous left ventricular
      assist device.

PMID- 29589377
TI  - Acute coronary syndrome in a patient with a history of ascending thoracic aortic
      surgery using the Cabrol technique.

PMID- 29589378
TI  - The inaccurate resolution of contemporary digital angiography, but not the
      anatomic complexity itself, primarily impairs the invasive evaluation of ostial
      coronary lesions.

PMID- 29589379
TI  - Results and factors associated with adverse outcome after tricuspid valve
      replacement.
AB  - BACKGROUND AND AIM: This retrospective analysis of patients with severe tricuspid
      valve disease, who underwent tricuspid valve replacement (TVR) for either
      tricuspid regurgitation or stenosis, has been designed to determine the factors
      that predict poor hospital and long-term survival. METHODS: The study population
      comprised 86 patients, 65 women and 21 men, who underwent TVR with or without con
      comitant surgical procedures between 2000 and 2010 at our institution. Patients
      with Ebstein's or other complex congenital anomalies were excluded from the
      study. RESULTS: Average age at operation was 58.5 +/- 12.5 (range 16-78) years.
      Fifty (58.1%) patients had undergone previous cardiac surgery. Forty-two patients
      were in New York Heart Association (NYHA) class III functional capacity, and 18
      were in class IV. Symptoms of right heart failure (HF) were present in 66
      patients, of whom 19 had ascites. Bioprosthetic tricuspid valves were implanted
      in 84 patients and mechanical prostheses in two. The choice to proceed to TVR
      instead of repair was individualised and based on the surgeon's preference. In
      hospital mortality was 18 (20.9%) patients, caused mainly by multi-organ and HF,
      and was significantly related to NYHA class and symptoms of right HF before
      surgery, with no mortality in patients with NYHA class I and II, 19% mortality
      with NYHA class III, and 55.6% mortality with NYHA class IV. Eighteen (20.9%)
      patients died during postoperative follow-up. The main risk factors associated
      with perioperative mortality were: the presence of severe symptoms at the time of
      surgery, low preoperative haematocrit, postoperative complications, postoperative
      ventilation time longer than 72 h, and renal failure requiring dialysis. Elevated
      pulmonary artery pressure, preoperative symptoms of right HF, and low haematocrit
      unfavourably affected the long-term results. CONCLUSIONS: Many earlier studies
      reported high mortality and morbidity after TVR in both early and late
      postoperative peri-ods. Our main finding is that good outcomes for TVR are
      achievable in properly selected patients. Sixty of 86 patients in our group had
      preoperative NYHA functional class III and IV, which suggests that surgical
      timing was late in many patients. Based on our observations, we propose that
      surgical correction of severe tricuspid valve disease should be considered before
      the development of advanced HF, when patients are asymptomatic or only
      oligosymptomatic.

PMID- 29589380
TI  - Massage, reflexology and other manual methods for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour, and this may contribute towards the popularity of
      complementary methods of pain management. This review examined the evidence
      currently available on manual methods, including massage and reflexology, for
      pain management in labour. This review is an update of the review first published
      in 2012. OBJECTIVES: To assess the effect, safety and acceptability of massage,
      reflexology and other manual methods to manage pain in labour. SEARCH METHODS:
      For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register
      (30 June 2017), the Cochrane Central Register of Controlled Trials (CENTRAL;
      2017, Issue 6), MEDLINE (1966 to 30 June 2017, CINAHL (1980 to 30 June 2017), the
      Australian New Zealand Clinical Trials Registry (4 August 2017), Chinese Clinical
      Trial Registry (4 August 2017), ClinicalTrials.gov, (4 August 2017), the National
      Center for Complementary and Integrative Health (4 August 2017), the WHO
      International Clinical Trials Registry Platform (ICTRP) (4 August 2017) and
      reference lists of retrieved trials. SELECTION CRITERIA: We included randomised
      controlled trials comparing manual methods with standard care, other non
      pharmacological forms of pain management in labour, no treatment or placebo. We
      searched for trials of the following modalities: massage, warm packs, thermal
      manual methods, reflexology, chiropractic, osteopathy, musculo-skeletal
      manipulation, deep tissue massage, neuro-muscular therapy, shiatsu, tuina,
      trigger point therapy, myotherapy and zero balancing. We excluded trials for pain
      management relating to hypnosis, aromatherapy, acupuncture and acupressure; these
      are included in other Cochrane reviews. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trial quality, extracted data and checked data for
      accuracy. We contacted trial authors for additional information. We assessed the
      quality of the evidence using the GRADE approach. MAIN RESULTS: We included a
      total of 14 trials; 10 of these (1055 women) contributed data to meta-analysis.
      Four trials, involving 274 women, met our inclusion criteria but did not
      contribute data to the review. Over half the trials had a low risk of bias for
      random sequence generation and attrition bias. The majority of trials had a high
      risk of performance bias and detection bias, and an unclear risk of reporting
      bias. We found no trials examining the effectiveness of reflexology.MassageWe
      found low-quality evidence that massage provided a greater reduction in pain
      intensity (measured using self-reported pain scales) than usual care during the
      first stage of labour (standardised mean difference (SMD) -0.81, 95% confidence
      interval (CI) -1.06 to -0.56, six trials, 362 women). Two trials reported on pain
      intensity during the second and third stages of labour, and there was evidence of
      a reduction in pain scores in favour of massage (SMD -0.98, 95% CI -2.23 to 0.26,
      124 women; and SMD -1.03, 95% CI -2.17 to 0.11, 122 women). There was very low
      quality evidence showing no clear benefit of massage over usual care for the
      length of labour (in minutes) (mean difference (MD) 20.64, 95% CI -58.24 to
      99.52, six trials, 514 women), and pharmacological pain relief (average risk
      ratio (RR) 0.81, 95% CI 0.37 to 1.74, four trials, 105 women). There was very low
      quality evidence showing no clear benefit of massage for assisted vaginal birth
      (average RR 0.71, 95% CI 0.44 to 1.13, four trials, 368 women) and caesarean
      section (RR 0.75, 95% CI 0.51 to 1.09, six trials, 514 women). One trial reported
      less anxiety during the first stage of labour for women receiving massage (MD 
      16.27, 95% CI -27.03 to -5.51, 60 women). One trial found an increased sense of
      control from massage (MD 14.05, 95% CI 3.77 to 24.33, 124 women, low-quality
      evidence). Two trials examining satisfaction with the childbirth experience
      reported data on different scales; both found more satisfaction with massage,
      although the evidence was low quality in one study and very low in the other.Warm
      packsWe found very low-quality evidence for reduced pain (Visual Analogue
      Scale/VAS) in the first stage of labour (SMD -0.59, 95% CI -1.18 to -0.00, three
      trials, 191 women), and the second stage of labour (SMD -1.49, 95% CI -2.85 to 
      0.13, two trials, 128 women). Very low-quality evidence showed reduced length of
      labour (minutes) in the warm-pack group (MD -66.15, 95% CI -91.83 to -40.47; two
      trials; 128 women).Thermal manual methodsOne trial evaluated thermal manual
      methods versus usual care and found very low-quality evidence of reduced pain
      intensity during the first phase of labour for women receiving thermal methods
      (MD -1.44, 95% CI -2.24 to -0.65, one trial, 96 women). There was a reduction in
      the length of labour (minutes) (MD -78.24, 95% CI -118.75 to -37.73, one trial,
      96 women, very low-quality evidence). There was no clear difference for assisted
      vaginal birth (very low-quality evidence). Results were similar for cold packs
      versus usual care, and intermittent hot and cold packs versus usual care, for
      pain intensity, length of labour and assisted vaginal birth.Music One trial that
      compared manual methods with music found very low-quality evidence of reduced
      pain intensity during labour in the massage group (RR 0.40, 95% CI 0.18 to 0.89,
      101 women). There was no evidence of benefit for reduced use of pharmacological
      pain relief (RR 0.41, 95% CI 0.16 to 1.08, very low-quality evidence).Of the
      seven outcomes we assessed using GRADE, only pain intensity was reported in all
      comparisons. Satisfaction with the childbirth experience, sense of control, and
      caesarean section were rarely reported in any of the comparisons. AUTHORS'
      CONCLUSIONS: Massage, warm pack and thermal manual methods may have a role in
      reducing pain, reducing length of labour and improving women's sense of control
      and emotional experience of labour, although the quality of evidence varies from
      low to very low and few trials reported on the key GRADE outcomes. Few trials
      reported on safety as an outcome. There is a need for further research to address
      these outcomes and to examine the effectiveness and efficacy of these manual
      methods for pain management.

PMID- 29589381
TI  - Continued Innovation in Respiratory Care: The Importance of Inhaler Devices.
AB  - When it comes to the use in inhalers in the management of chronic obstructive
      pulmonary diseases, there are many options, considerations and challenges, which
      health care professionals need to address. Considerations for prescribing and
      dispensing, administering and following up, education, and adherence; all of
      these factors impact on treatment success and all are intrinsically linked to the
      device selected. This review brings together relevant evidence, real-life data
      and practice tools to assist health care professionals in making decisions about
      the use of inhalers in the management of chronic obstructive pulmonary diseases.
      It covers some of the key technical device issues to be considered, the evidence
      behind the role of inhalers in disease control, population studies which link
      behaviors and adherence to inhaler devices as well as practice advice on inhaler
      technique education and the advantages and disadvantages in selecting different
      inhaler devices. Finally, a list of key considerations to aid health care
      providers in successfully managing the use of inhaler devices are summarized.

PMID- 29589382
TI  - The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke
      Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells.
AB  - BACKGROUND: Recent studies show that mitophagy, the autophagy-dependent turnover
      of mitochondria, mediates pulmonary epithelial cell death in response to
      cigarette smoke extract (CSE) exposure and contributes to the development of
      emphysema in vivo during chronic cigarette smoke (CS) exposure, although the
      underlying mechanisms remain unclear. METHODS: In this study, we investigated the
      role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell
      (Beas-2B) death. We also investigated the role of a phosphodiesterase 4
      inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. RESULTS:
      Our results demonstrated that CSE induces mitophagy in Beas-2B cells through
      mitochondrial dysfunction and increased the expression levels of the mitophagy
      regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial
      fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death
      was significantly increased in Beas-2B cells exposed to CSE but was decreased by
      small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in
      Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by
      inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected
      against cell death and increased cell viability, as determined by the lactate
      dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells
      exposed to CSE. CONCLUSION: These findings suggest that roflumilast plays a
      protective role in CS-induced mitophagy-dependent cell death.

PMID- 29589383
TI  - Bone Health in Adrenal Disorders.
AB  - Secondary osteoporosis resulting from specific clinical disorders may be
      potentially reversible, and thus continuous efforts to find and adequately treat
      the secondary causes of skeletal fragility are critical to ameliorate fracture
      risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the
      hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary
      aldosteronism are receiving particularly great attention due to their high
      morbidity and mortality mainly by increasing cardiovascular risk. Interestingly,
      there is accumulating experimental and clinical evidence that adrenal hormones
      may have direct detrimental effects on bone metabolism as well. Thus, the present
      review discusses the possibility of adrenal disorders, especially focusing on
      pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

PMID- 29589384
TI  - Pathophysiology of Type 2 Diabetes in Koreans.
AB  - The pathophysiology of type 2 diabetes is characterized by variable degrees of
      insulin resistance and impaired insulin secretion. Both genetic and environmental
      factors serve as etiologic factors. Recent genetic studies have identified at
      least 83 variants associated with diabetes. A significant number of these loci
      are thought to be involved in insulin secretion, either through beta-cell
      development or beta-cell dysfunction. Environmental factors have changed rapidly
      during the past half century, and the increased prevalence of obesity and
      diabetes can be attributed to these changes. Environmental factors may affect
      epigenetic changes and alter susceptibility to diabetes. A recent epidemiologic
      study revealed that Korean patients with type 2 diabetes already had impaired
      insulin secretion and insulin resistance 10 years before the onset of diabetes.
      Those who developed diabetes showed impaired beta-cell compensation with an
      abrupt decrease in insulin secretion during the last 2 years before diabetes
      developed. The retrograde trajectory of the disposition index differed according
      to the baseline subgroups of insulin secretion and insulin sensitivity. We hope
      that obtaining a more detailed understanding of the perturbations in the major
      pathophysiologic process of diabetes on the individual level will eventually lead
      to the implementation of precision medicine and improved patient outcomes.

PMID- 29589385
TI  - Evolution of Diabetes Care in Hong Kong: From the Hong Kong Diabetes Register to
      JADE-PEARL Program to RAMP and PEP Program.
AB  - The rapid increase in diabetes prevalence globally has contributed to large
      increases in health care expenditure on diabetic complications, posing a major
      health burden to countries worldwide. Asians are commonly observed to have poorer
      beta-cell function and greater insulin resistance compared to the Caucasian
      population, which is attributed by their lower lean body mass and central
      obesity. This "double phenotype" as well as the rising prevalence of young onset
      diabetes in Asia has placed Asians with diabetes at high risk of cardiovascular
      and renal complications, with cancer emerging as an important cause of morbidity
      and mortality. The experience from Hong Kong had demonstrated that a multifaceted
      approach, involving team-based integrated care, information technological
      advances, and patient empowerment programs were able to reduce the incidence of
      diabetic complications, hospitalizations, and mortality. System change and public
      policies to enhance implementation of such programs may provide solutions to
      combat the burgeoning health problem of diabetes at a societal level.

PMID- 29589388
TI  - The Significance of Having an Excellent Patient's Comfort with Thyroid Core
      Needle Biopsy.

PMID- 29589386
TI  - Association of Adipokines with Development and Progression of Nonalcoholic Fatty
      Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting 30%
      of the general population and 40% to 70% of obese individuals. Adipose tissue
      plays a crucial role in its pathogenesis, as it produces and secretes pro- and
      anti-inflammatory cytokines called adipokines. Adiponectin and leptin have well
      determined actions in terms of NAFLD pathophysiology. Adiponectin deficiency is
      associated with a pro-inflammatory condition, as it is observed in obesity and
      other metabolic disorders. On the other hand, increased leptin levels, above the
      normal levels, act as a pro-inflammatory stimulus. Regarding other adipokines
      (resistin, visfatin, chemerin, retinol-binding protein 4, irisin), data about
      their contribution to NAFLD pathogenesis and progression are inconclusive. In
      addition, pharmacological agents like thiazolidinediones (pioglitazone and
      rosiglitazone), that are used in the management of NAFLD exert favourable effects
      on adipokine levels, which in turn may contribute to the improvement of liver
      function. This review summarizes the current knowledge and developments in the
      association between adipokines and NAFLD and discusses possible therapeutic
      implications targeting the modulation of adipokine levels as a potential tool for
      the treatment of NAFLD.

PMID- 29589387
TI  - Evidence of the Possible Harm of Endocrine-Disrupting Chemicals in Humans:
      Ongoing Debates and Key Issues.
AB  - Evidence has emerged that endocrine-disrupting chemicals (EDCs) can produce
      adverse effects, even at low doses that are assumed safe. However, systemic
      reviews and meta-analyses focusing on human studies, especially of EDCs with
      short half-lives, have demonstrated inconsistent results. Epidemiological studies
      have insuperable methodological limitations, including the unpredictable net
      effects of mixtures, non-monotonic dose-response relationships, the non-existence
      of unexposed groups, and the low reliability of exposure assessment. Thus,
      despite increases in EDC-linked diseases, traditional epidemiological studies
      based on individual measurements of EDCs in bio-specimens may fail to provide
      consistent results. The exposome has been suggested as a promising approach to
      address the uncertainties surrounding human studies, but it is never free from
      these methodological issues. Although exposure to EDCs during critical
      developmental periods is a major concern, continuous exposure to EDCs during non
      critical periods is also harmful. Indeed, the evolutionary aspects of epigenetic
      programming triggered by EDCs during development should be considered because it
      is a key mechanism for developmental plasticity. Presently, living without EDCs
      is impossible due to their omnipresence. Importantly, there are lifestyles which
      can increase the excretion of EDCs or mitigate their harmful effects through the
      activation of mitohormesis or xenohormesis. Effectiveness of lifestyle
      interventions should be evaluated as practical ways against EDCs in the real
      world.

PMID- 29589389
TI  - Validity and Reliability of the Korean Version of the Hyperthyroidism Symptom
      Scale.
AB  - BACKGROUND: Thyrotoxicosis is a common disease resulting from an excess of
      thyroid hormones, which affects many organ systems. The clinical symptoms and
      signs are relatively nonspecific and can vary depending on age, sex,
      comorbidities, and the duration and cause of the disease. Several symptom rating
      scales have been developed in an attempt to assess these symptoms objectively and
      have been applied to diagnosis or to evaluation of the response to treatment. The
      aim of this study was to assess the reliability and validity of the Korean
      version of the hyperthyroidism symptom scale (K-HSS). METHODS: Twenty-eight
      thyrotoxic patients and 10 healthy subjects completed the K-HSS at baseline and
      after follow-up at Seoul National University Bundang Hospital. The correlation
      between K-HSS scores and thyroid function was analyzed. K-HSS scores were
      compared between baseline and follow-up in patient and control groups. Cronbach's
      alpha coefficient was calculated to demonstrate the internal consistency of K
      HSS. RESULTS: The mean age of the participants was 34.7+/-9.8 years and 13
      (34.2%) were men. K-HSS scores demonstrated a significant positive correlation
      with serum free thyroxine concentration and decreased significantly with improved
      thyroid function. K-HSS scores were highest in subclinically thyrotoxic subjects,
      lower in patients who were euthyroid after treatment, and lowest in the control
      group at follow-up, but these differences were not significant. Cronbach's alpha
      coefficient for the K-HSS was 0.86. CONCLUSION: The K-HSS is a reliable and valid
      instrument for evaluating symptoms of thyrotoxicosis in Korean patients.

PMID- 29589390
TI  - High Brachial Ankle Pulse Wave Velocity as a Marker for Predicting Coronary
      Artery Stenosis in Patients with Type 2 Diabetes.
AB  - BACKGROUND: We evaluated the ability of brachial ankle pulse wave velocity
      (baPWV) to predict coronary artery stenosis (CAS) in patients with type 2
      diabetes, and compared the predictive power of baPWV to that of well-known
      cardiovascular disease (CVD) risk calculators. METHODS: The study group included
      83 consecutive patients over 30 years old with type 2 diabetes who complained of
      vague chest discomfort. An automatic pulse waveform analyzer was used to measure
      baPWV. CAS was measured using multi-slice computed tomographic (MSCT)
      angiography. RESULTS: Age, maximal baPWV, duration of diabetes, current smoking,
      the UK Prospective Diabetes Study (UKPDS) Risk Engine score, American College of
      Cardiology/American Heart Association (ACC/AHA) risk estimator score, the
      Framingham risk calculator score, and coronary artery calcium score were greater
      in patients with CAS than in those without CAS. An area under the curve (AUC)
      indicative of a predictive value for CAS (>=20%) was found for several
      parameters. The AUC of maximal baPWV, the UKPDS Risk Engine, the ACC/AHA ASCVD
      risk estimator, and the Framingham risk calculator were 0.672 (95% confidence
      interval [CI], 0.554 to 0.785; P=0.010), 0.777 (95% CI, 0.675 to 0.878; P<0.001),
      0.763 (95% CI, 0.660 to 0.866; P<0.001), and 0.736 (95% CI, 0.629 to 0.843;
      P<0.001), respectively. The optimal cutoff value of baPWV for the detection of
      CAS was 1,650 cm/sec (sensitivity, 68.9%; specificity, 63.2%). CONCLUSION:
      Maximal baPWV was closely related with CAS detected by MSCT coronary angiography
      in patients with type 2 diabetes. baPWV has the potential to be a useful,
      noninvasive screening tool for the prediction of occult CAS in patients with type
      2 diabetes.

PMID- 29589391
TI  - Effects of Serum Albumin, Calcium Levels, Cancer Stage and Performance Status on
      Weight Loss in Parathyroid Hormone-Related Peptide Positive or Negative Patients
      with Cancer.
AB  - BACKGROUND: A recent animal study showed that parathyroid hormone-related peptide
      (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning,
      and we previously demonstrated that PTHrP predicts weight loss (WL) in patients
      with cancer. In this study, we investigated whether prediction of WL by PTHrP is
      influenced by clinical factors such as serum albumin, corrected calcium levels,
      cancer stage, and performance status (PS). METHODS: A cohort of 219 patients with
      cancer whose PTHrP level was measured was enrolled and followed for body weight
      (BW) changes. Subjects were divided into two groups by serum albumin (cutoff
      value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage
      (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4),
      respectively. Clinically significant WL was defined as either percent of BW
      change (% BW) <-5% or % BW <-2% plus body mass index (BMI) <20 kg/m2. RESULTS:
      After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically
      significant WL. A positive PTHrP level was associated with a 2-fold increased
      risk of WL after adjusting for age, baseline BMI, serum albumin, corrected
      calcium level, cancer stage, and PS. The effect of PTHrP on WL remained
      significant in patients with low serum albumin, stage 4 cancer, and good PS.
      Regardless of calcium level, the effect of PTHrP on WL was maintained, although
      there was an additive effect of higher calcium and PTHrP levels. CONCLUSION:
      Early recognition of patients with advanced cancer who are PTHrP positive with
      hypercalcemia or hypoalbuminemia is needed for their clinical management.

PMID- 29589392
TI  - Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum
      Stress in Pancreatic beta-Cells.
AB  - BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma
      (PPARgamma) is a useful therapeutic target for obesity and diabetes, but its role
      in protecting beta-cell function and viability is unclear. METHODS: To identify
      the potential functions of PPARgamma in beta-cells, we treated mouse insulinoma 6
      (MIN6) cells with the PPARgamma agonist pioglitazone in conditions of
      lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS:
      Palmitate-treated cells incubated with pioglitazone exhibited significant
      improvements in glucose-stimulated insulin secretion and the repression of
      apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine
      diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the
      palmitate-induced expression of inflammatory cytokines (tumor necrosis factor
      alpha, interleukin 6 [IL-6], and IL-1beta) and ER stress markers (phosphor
      eukaryotic translation initiation factor 2alpha, glucose-regulated protein 78
      [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous
      protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER
      stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective
      effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK
      Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks.
      Pioglitazone remarkably reduced the expression of ATF6alpha, GRP78, and monocyte
      chemoattractant protein-1, prevented alpha-cell infiltration into the pancreatic
      islets, and upregulated glucose transporter 2 (Glut2) expression in beta-cells.
      Moreover, the preservation of beta-cells by pioglitazone was accompanied by a
      significant reduction of blood glucose levels. CONCLUSION: Altogether, these
      results support the proposal that PPARgamma agonists not only suppress insulin
      resistance, but also prevent beta-cell impairment via protection against ER
      stress and inflammation. The activation of PPARgamma might be a new therapeutic
      approach for improving beta-cell survival and insulin secretion in patients with
      diabetes mellitus.

PMID- 29589393
TI  - A Comparison of Ultrasound-Guided Fine Needle Aspiration versus Core Needle
      Biopsy for Thyroid Nodules: Pain, Tolerability, and Complications.
AB  - BACKGROUND: To compare pain, tolerability, and complications associated with fine
      needle aspiration (FNA) versus core needle biopsy (CNB). METHODS: FNAs were
      performed using 23-gauge needles and CNBs were performed using 18-gauge double
      action spring-activated needles in 100 patients for each procedure. Patients were
      asked to record a pain score using a 10-cm visual analog scale and procedure
      tolerability. Complications and number of biopsies were recorded. RESULTS: The
      median pain scores were similar for the FNA and CNB approaches during and 20
      minutes after the biopsy procedures (3.7 vs. 3.6, P=0.454; 0.9 vs. 1.1, P=0.296,
      respectively). The procedure was tolerable in all 100 FNA patients and in 97 CNB
      patients (P=0.246). The mean number of biopsies was fewer in the CNB group (1.4
      vs. 1.2, P=0.002). By subgroup analysis (staff vs. non-staff), no significant
      difference was detected in any parameter. There were no major complications in
      either group, but three patients who underwent CNB had minor complications
      (P=0.246). CONCLUSION: FNA and CNB show no significant differences for diagnosing
      thyroid nodules in terms of pain, tolerability, or complications.

PMID- 29589394
TI  - Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic
      Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human
      malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic
      agent used to treat various metastatic cancers. However, prolonged use results in
      various side effects and drug resistance. Flavonoids, such as baicalein, are
      accepted chemotherapeutic and dietary chemopreventive agents with many
      advantages, such as greater accessibility, affordability, and lower toxicity,
      compared with traditional chemotherapy agents. In this study, we evaluated
      whether baicalein enhances the effects of docetaxel on apoptosis and metastasis
      in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or
      docetaxel individually and in combination. Cell viability was measured by MTT
      (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by
      fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic
      (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial
      growth factor [VEGF], transforming growth factor beta [TGF-beta], E-cadherin, and
      N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen
      activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR])
      proteins was determined by Western blot analysis. RESULTS: The combination of
      baicalein (50 or 100 MUM) and docetaxel (10 nM) significantly inhibited
      proliferation and induced apoptosis compared with monotherapies. The combination
      treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF
      beta1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2
      and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The
      combination of baicalein and docetaxel effectively induced apoptosis and
      inhibited metastasis in 8505c cells through downregulation of apoptotic and
      angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in
      8505c cells. These results suggest that baicalein enhances the anticancer effects
      of docetaxel in ATC.

PMID- 29589395
TI  - Active Surveillance of Papillary Thyroid Microcarcinoma: A Mini-Review from Korea
      (Endocrinol Metab 2017;32:399-406, Tae Yong Kim et al.).

PMID- 29589396
TI  - Erratum: Addendum of Informed Consent Statements.
AB  - This corrects the article on p. 110 in vol. 30, PMID: 25491781 This corrects the
      article on p. 395 in vol. 30, PMID: 25491785.

PMID- 29589397
TI  - Perspectives and unmet needs in polymyalgia rheumatica. Providing the fundamental
      framework for the development of new treatment regimes in polymyalgia rheumatica.
AB  - Polymyalgia rheumatica is effectively treated with glucocorticoids. However,
      glucocorticoid treatment can cause numerous and potentially serious side effects.
      Therefore, lowest effective dose and shortest duration to control disease is
      aimed for and glucocorticoid-sparing treatments are needed. Nevertheless,
      development of treatment regimens in PMR has been hampered by the lack of
      reliable classification criteria and evidence-based outcome measures. In this
      editorial, we discuss the need for valid classification criteria in PMR, the
      strengths and limitations of the ACR/EULAR 2012 provisional classification
      criteria for PMR and the need of validation and possible refining of the
      criteria.

PMID- 29589398
TI  - Pathogenesis of polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown
      cause, almost exclusively occurring in people aged over 50 and often associated
      with giant cell arteritis. The evidence that PMR occurs almost exclusively in
      individuals aged over 50 may indicate that age-related immune alterations in
      genetically predisposed subjects contribute to development of the disease.
      Several infectious agents have been investigated as possible triggers of PMR even
      though the results are inconclusive. Activation of the innate and adaptive immune
      systems has been proved in PMR patients as demonstrated by the activation of
      dendritic cells and monocytes/macrophages and the altered balance between Th17
      and Treg cells. Disturbed B cell distribution and function have been also
      demonstrated in PMR patients suggesting a pathogenesis more complex than
      previously imagined. In this review we will discuss the recent findings regarding
      the pathogenesis of PMR.

PMID- 29589399
TI  - Contribution of the new 2012 EULAR/ACR classification criteria for the diagnosis
      of polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory
      disorders in people aged over 50. It is characterized by aching and prolonged
      morning stiffness in the shoulder and pelvic girdles and neck. To date there are
      no specific diagnostic tests, and in clinical practice the diagnosis of PMR
      remains based on its characteristic clinical manifestations, laboratory evidence
      of systemic inflammation, rapid response to low doses of glucocorticoids and
      exclusion of other disorders that may present with proximal pain and stiffness.
      For classification purposes, several criteria have been proposed over time based
      on retrospective clinical series, but none have been validated and received
      universal acceptance. Recently, an international collaborative initiative between
      the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica
      classification criteria. In this review, the provisional 2012 EULAR/ACR
      classification criteria will be presented and their contribution for the
      diagnosis of polymyalgia rheumatica will be discussed.

PMID- 29589400
TI  - The real evidence for polymyalgia rheumatica as a paraneoplastic syndrome.
AB  - The aim of this study was to systematically consider the evidence for polymyalgia
      rheumatica (PMR) as a paraneoplastic disease. A systematic review of Medline and
      Embase was conducted from their inception to February 2017. Risk of bias was
      assessed using the Newcastle-Ottawa tool. Data were extracted regarding the PMR
      cancer association, the types of cancer associated with PMR and the presentation
      of PMR patients subsequently diagnosed with cancer. Twenty-three full text
      articles were reviewed from the 1174 unique references identified in the search.
      Nine articles were included in the final review. There was some evidence of an
      association between PMR and cancer in the short-term (first 6 to 12 months after
      diagnosis), but no evidence of an association after this time. Limited evidence
      suggests that lymphoma, prostate and haematological cancers may be those cancers
      more commonly diagnosed in those with PMR. There was little evidence to suggest
      what presenting features may be associated with the development of cancer. There
      is little evidence of PMR as a true paraneoplastic disease. However, there is
      reason to be cautious when making the diagnosis of PMR. Clinicians should be
      aware of this potential association both prior to making a diagnosis and
      throughout the course of the condition.

PMID- 29589401
TI  - Comorbidity in polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is the commonest inflammatory rheumatic disease
      affecting older people. The current mainstay of treatment is long-term oral
      glucocorticoid therapy. Management of these patients in clinical practice is
      often complicated by the presence of comorbidity. Comorbidity might be due to
      shared risk factors such as age, sex, or genetic background; to the presence of
      the disease itself; or to adverse effects of glucocorticoid therapy.
      Cardiovascular disease, osteoporosis/fracture, metabolic and ocular comorbidity
      are of particular interest to clinicians because of their relationship to
      glucocorticoid therapy and the relevance to clinical treatment decisions
      regarding glucocorticoid tapering. Patients at high risk of exacerbation of
      comorbidity by glucocorticoid therapy may be considered for adjunctive steroid
      sparing therapies and thus may need specialist management. From a public health
      perspective, with the ageing population the prevalence of PMR is predicted to
      increase; accurate data on comorbidity will be needed for planning and delivery
      of healthcare services.

PMID- 29589402
TI  - The role of the general practitioner and the out-of-hospital public
      rheumatologist in the diagnosis and follow-up of patients with polymyalgia
      rheumatica.
AB  - Polymyalgia rheumatica (PMR) is a chronic inflammatory disease characterized by
      shoulder and pelvic girdle pain. Its onset peaks around the age of 75; the
      prevalence increases until the age of 90 and it is more frequent in females.
      Diagnosis is mostly performed on the basis of symptoms. An increase of serum
      inflammatory markers is indicative, but not essential, while therapy is mainly
      based on glucocorticoids. Since there is no universal agreement about diagnostic
      criteria for PMR, its detection is still difficult. There are discordant opinions
      about the fact that PMR can be recognised and managed by general practitioners
      (GPs), while patients with atypical features need to be referred to the
      rheumatologist. In the Italian setting, the absence of recent epidemiological
      studies is associated with the total lack of a research protocol in primary care,
      from which relevant information could be derived. The out-of-hospital public
      rheumatologist is a peculiar figure of the Italian National Health System, who
      takes care of outpatients. Although differences between the different Italian
      regional health services exist, this professional figure has proved to be
      effective in reducing delay and increasing accuracy in PMR diagnosis.

PMID- 29589403
TI  - Imaging in polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause
      clinically characterized by pain and prolonged morning stiffness affecting the
      shoulders and often the pelvic girdle and neck. Imaging has substantially
      contributed to defining PMR as a disease mainly involving extra-articular
      structures. This review article analyses the role of the different imaging
      techniques in the diagnosis and follow-up of patients with PMR with particular
      emphasis on the role of ultrasound, PET/CT and MRI.

PMID- 29589404
TI  - Update on treatment of polymyalgia rheumatica.
AB  - Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic
      disease in the elderly after rheumatoid arthritis. It is clinically characterised
      by pain and stiffness in the neck, proximal shoulder and hip girdle.
      Glucocorticoids (GCs) are the cornerstone of PMR treatment, but they are
      associated with potentially severe side effects. Among GC-sparing agents,
      methotrexate revealed a modest benefit in clinical trials, and recently, there
      have been promising reports from tocilizumab. In this review, we summarize the
      available evidence on the treatment of PMR and the possible role in the future of
      other agents under investigation.

PMID- 29589405
TI  - Static and dynamic plantar pressure distribution in amateur marathon runners.
AB  - BACKGROUND: The aim of the study was to compare the static and dynamic plantar
      pressure profiles of amateur marathon runners with sedentary cohorts. RESEARCH
      QUESTIONS: Are there differences in the plantar pressures of these two
      populations? Is there a correlation between body mass and BMI with plantar
      loading? METHODS: The study involved 43 runners involved in marathon training and
      30 age-matched untrained individuals. Plantar pressure was measured using a
      baropodometric system. RESULTS: The marathon runners showed greater forefoot
      plantar pressure of the dominant extremity in the static condition and reduced
      medial plantar pressure of both extremities in the dynamic condition. A
      correlation was observed between body mass and BMI with mean plantar pressure
      only in the marathon group and only for the dominant extremity in the dynamic
      condition. CONCLUSIONS: Marathon training may modify the forefoot plantar loading
      characteristics of the dominant extremity during static conditions and increase
      lateral plantar pressure of both extremities in a dynamic (gait) condition.

PMID- 29589406
TI  - Improved cardiorespiratory fitness following moderate exercise may encourage
      inactive people for doable and sustainable behavioral change.
AB  - BACKGROUND: Global physical inactivity pandemic is responsible for more than 5
      million deaths annually through its effects on non-communicable diseases. This
      requires urgent intervention. OBJECTIVE: To investigate associations of physical
      activity with cardiovascular fitness in a cross-sectional retrospective
      observational study. Data were collected for 21 years from 2530 healthy
      volunteers and athletes representing the entire spectrum of physical activity
      from the totally inactive sedentary persons to the highly trained national
      athletes. METHODS: Cardiac fitness was investigated echocardiographically, which
      is characterized by reduced resting heart rate (RHR), increased relative left
      ventricular muscular mass (rLVMM), improved left ventricular diastolic function
      (characterized by the ratio of early to late ventricular peak velocities, E/A)
      and peak exercise oxygen consumption. RESULTS: We found that even moderate
      exercise is associated with improved cardiac characteristics. With increasing
      exercise level, the RHR decreased from 69 to 63.3*, 61.4, 58.6*, 56.1 and
      55.8/min in the non-athletes, leisure athletes, lower class athletes, 2nd class
      athletes, 1st class athletes and national athletes, respectively.b While the
      rLVMM was increased from 64.6 to 70.7*, 76.3*, 78.5, 86.7*and 88.9 in the same
      groups. The E/A ratio also increased from 1.71 to 1.72, 1.85*, 2.04* in the non
      athletes, leisure athletes, lower class athletes, and 2nd class athletes,
      respectively, but then decreased to 1.92 and 1.98 in the 1st class athletes and
      national athletes. The largest exerciseinduced improvement of cardiac fitness was
      observed between the inactive and the least active group, which didn't increase
      further in the highly trained national athletes enduring up to 20 training hours
      per week. CONCLUSIONS: Our findings indicate that cardiac fitness can be improved
      by moderate exercise in sedentary persons. This information would help physicians
      to encourage inactive patients, who find physical exercise intimidating, for
      doable and sustainable behavioral change.

PMID- 29589407
TI  - Validity and reliability of an inertial device (WIMU PROTM) to quantify physical
      activity level through steps measurement.
AB  - BACKGROUND: Currently, there is an increase in the application of accelerometers
      to quantify physical activity level through daily steps, and therefore, it is
      required that the devices are valid and reliable. The current study tested (i)
      the validity of the WIMU PROTM inertial device in steps detection and (ii) the
      inter-device reliability for steps measurement. METHODS: Ten endurance-trained
      men volunteered to participate in this study (height: 1.78 +/- 0.05 m; body mass:
      72.96 +/- 4.2 kg). Twelve trials of 40.32 m at different speeds (four trials at
      each speed) were performed: (a) walking (<5 km/h), (b) jogging (5-10 km/h) and
      running (10-15 km/h). The video analysis was used as criterion to assess
      validity, while, two WIMU PROTM inertial devices were compared to assess between-
      unit reliability. RESULTS: A near-perfect validity between video analysis and
      WIMU PROTM (ICC = 0.999; Bias = 0.03) and a very good reliability between WIMU
      PROTM devices (Bias = -0.01; CV = 0.02%) was found. The highest values were found
      at walking (ICC = 0.999) and the lowest values were found at running (ICC =
      0.995). CONCLUSIONS: WIMU PROTM is a reliable and valid device to quantify
      physical activity level through steps measurement.

PMID- 29589408
TI  - High-intensity interval training in overweight and obese children and
      adolescents: systematic review and meta-analysis.
AB  - INTRODUCTION: While High Intensity Interval Training is praised in many
      populations for its beneficial effects on body composition and cardiometabolic
      health, its use among obese youth remain uncertain. This study aimed at
      determining whether HIIT is effective to improve aerobic fitness and reduce
      cardiometabolic risk factors in overweight and obese youth. EVIDENCE ACQUISITION:
      A systematic search was conducted and articles reporting studies that
      investigated the effects of HIIT in 6 to 18-year-old youth were eligible. Meta
      analyses were performed when appropriate. EVIDENCE SYNTHESIS: 15 studies were
      included for the systematic review and meta-analyses. HIIT significantly improves
      maximal oxygen uptake [1.117 (95% CI=0.528 to 1.706), p<0.001], and reduces body
      mass [-0.295 (95%CI =-0.525 to -0.066), p<0.05], body fat [-0.786 (95%CI =-1.452
      to - 0.120), p<0.05], systolic and diastolic blood pressure [-1.026 (95% CI = 
      1.370 to -0.683), p<0.001; - 0.966 (95% CI =-1.628 to -0.304), p<0.01
      respectively], and the HOMA-IR [-1.589 (95%CI =-2.528 to -0.650), p<0.01].
      However, there is significant heterogeneity, and low to high inconsistency for
      most cardiometabolic risk factors and aerobic fitness. CONCLUSIONS: Although few
      studies have reported cardiometabolic risks, HIIT may also be as effective as
      traditional endurance continuous training to decrease blood pressure and insulin
      resistance. HIIT is effective to improve aerobic fitness, body composition, and
      cardiometabolic risk factors in obese youth, but data are insufficient to
      determine whether it is more effective than traditional continuous submaximal
      intensity exercise training.

PMID- 29589409
TI  - Physical fitness characteristics of Omani primary school children according to
      body mass index.
AB  - BACKGROUND: There is evidence that children with high cardiorespiratory fitness
      and normal body mass index (BMI) have less risk of non communicable diseases
      (NCDs), however limited research was undertaken in Omani children. Therefore the
      aims of the present study were to describe body composition and physical fitness
      of a large cohort of Omani school children of both genders, and to investigate
      the effects of weight status on physical fitness. METHODS: Three hundred and
      fourteen Omani school children aged 9 to 10 years old took part in anthropometric
      assessments, body composition and fitness tests, including handgrip strength, the
      basketball chest pass, broad jump, 20-m sprint, four 10-m shuttle agility, 30-s
      sit-up, and multistage fitness test (MSFT). RESULTS: Obese boys and girls
      performed worse than normal-weight children in sprint, agility and endurance. In
      addition, fitness measures in the overweight group and underweight groups were
      not significantly different from other groups, except a better handgrip strength
      and poorer MSFT in overweight compared to normal weight girls, and poorer agility
      performance in underweight girls compared to the three other groups. CONCLUSIONS:
      Most fitness measures are lower in obese Omani children, which suggests that they
      will be more at risk of developing NCDs later in life.

PMID- 29589410
TI  - Six weeks of multi-station program on the knee proprioception and performance of
      futsal players.
AB  - BACKGROUND: Proprioception and vertical jump are important parameters in the
      performance and prevention of injuries in futsal. However, very few studies have
      analyzed the role of multi-station exercises to improve these variables. The
      purpose of this study was to assess the effects of a six-week multi-station
      exercise program on knee joint position sense (JPS) and countermovement jump
      (CMJ) of futsal players. METHODS: Thirty-four male futsal players randomly
      classified into experimental (n = 17) or control group (n = 17). The experimental
      group included a multi-station exercise protocol to their training routines (2
      times/week - 6 weeks); the control group continued their training routines. All
      the players completed similar training routines outside of the multi-station
      exercises. Before (baseline), just after the intervention (Post6Wk) and four
      weeks later (Post10Wk), CMJ and knee JPS (absolute, relative and variable angular
      error: AAE, RAE and VAE, respectively) were evaluated. RESULTS: ANOVA showed that
      the experimental group significantly decreased VAE at Post10Wk compared to
      baseline, suggestive of greater proprioceptive precision, while the control group
      significantly increased AAE, RAE and VAE at Post10Wk compared to baseline. The
      experimental group exhibited lower and thus, better AAE and VAE than the control
      group at Post10Wk, although no significant differences were found at Post6Wk. No
      significant differences was found in the CMJ. CONCLUSIONS: A six weeks of multi
      station program may help improve proprioceptive precision of futsal players, even
      one month after finishing the 6-wk multi-station training program. However, this
      is not long enough to improve proprioceptive acuity and maximum vertical jump.
      Therefore, the meaningful of these results in term of performance are unclear.

PMID- 29589411
TI  - Dietetic- nutritional, physical and physiological recovery methods post
      competition in team sports. A review.
AB  - INTRODUCTION: To a proper recovery, is absolutely necessary to know that athletes
      with enhanced recovery after maximal exercise are likely to perform better in
      sports. Recovery strategies are commonly used in team sports despite limited
      scientific evidence to support their effectiveness in facilitating optimal
      recovery and the players spend a much greater proportion of their time recovering
      than they do in training. EVIDENCE ACQUISITION: According to authors, some
      studies investigated the effect of recovery strategies on physical performance in
      team sports, lack of experimental studies about the real origin of the fatigue,
      certify the need for further study this phenomenon. EVIDENCE SYNTHESIS: Thus,
      developing effective methods for helping athletes to recover is deemed essential.
      CONCLUSIONS: Therefore, the aim of this review is provide information for his
      practical application, based on scientific evidence about recovery in team
      sports.

PMID- 29589412
TI  - The validity and reliability of the my jump 2 app for measuring the reactive
      strength index and drop jump performance.
AB  - BACKGROUND: This is the first study to independently assess the concurrent
      validity and reliability of the My Jump 2 app for measuring drop jump
      performance. It is also the first to evaluate the app's ability to measure the
      reactive strength index (RSI). METHODS: Fourteen male sport science students
      (age: 29.5 +/- 9.9 years) performed three drop jumps from 20 cm and 40 cm
      (totalling 84 jumps), assessed via a force platform and the My Jump 2 app.
      Reported metrics included reactive strength index, jump height, ground contact
      time, and mean power. Measurements from both devices were compared using the
      intraclass correlation coefficient (ICC), Pearson product moment correlation
      coefficient (r), Cronbach's alpha (alpha), coefficient of variation (CV) and
      BlandAltman plots. RESULTS: Near perfect agreement was seen between devices at 20
      cm for RSI (ICC = 0.95) and contact time (ICC = 0.99) and at 40 cm for RSI (ICC =
      0.98), jump height (ICC = 0.96) and contact time (ICC = 0.92); with very strong
      agreement seen at 20 cm for jump height (ICC = 0.80). In comparison with the
      force plate the app showed good validity for RSI (20 cm: r = 0.94; 40 cm; r =
      0.97), jump height (20 cm: r = 0.80; 40 cm; r = 0.96) and contact time (20 cm =
      0.96; 40 cm; r = 0.98). CONCLUSIONS: The results of the present study show that
      the My Jump 2 app is a valid and reliable tool for assessing drop jump
      performance.

PMID- 29589413
TI  - Physiological demands of daily riding gaits in jockeys.
AB  - BACKGROUND: Jockeys should maintain a high level of physical fitness to meet the
      physical demands of horse racing. The aim of this study was to determine the
      physiological requirements of the riding gaits used regularly in training.
      METHODS: Eleven trainee jockeys performed a maximal incremental Wattbike cycle
      ergometer test. Mean absolute and relative oxygen uptake (VO2) and heart rate
      (HR) were recorded for the steady-state period during a walk, trot and canter.
      Energy expenditure (EE) and associated metabolic equivalent (MET) were also
      estimated. RESULTS: During a walk, trot and canter, relative mean VO2
      corresponded to 15 +/- 4%, 38 +/- 6%, 47 +/- 9% of VO2peak and mean HR
      corresponded to 48 +/- 6%, 60 +/- 6%, 71 +/- 7% of HRpeak respectively. Mean VO2
      and mean HR were significantly different amongst gaits; p <= 0.001. Walking
      required the lowest estimated EE of 2.25 +/- 0.6 kcal.min-1 (p <= 0.001; 2.4
      METs;) and it was significantly lower than trotting at 5.72 +/- 1.0 kcal.min-1 (p
      <= 0.001; 6.2 METs) and cantering at 7.10 +/- 1.8 kcal.min-1 (p <= 0.001; 7.7
      METs;). CONCLUSIONS & PRACTICAL APPLICATIONS: These riding activities are
      associated with relatively low physiological demand and alternate modes of
      exercise are recommended for trainee jockeys to ensure the demands of racing are
      met. Future research should investigate the physical training, both riding
      specific and general conditioning, jockeys perform in preparation for racing.

PMID- 29589414
TI  - Comparison of axillary nerve block duration using mepivacaine in non-insulin
      diabetic or renal insufficiency patients: a controlled observational matched
      multicentre trial.
AB  - BACKGROUND: Although studies in diabetic patients demonstrated delayed recovery
      after long-acting local anesthetic, its effects with short-acting LA remains to
      be determined. Using mepivacaine, the authors evaluated the duration of axillary
      nerve blocks in diabetic (DP), renal failure (creatinine clearance < 30 ml.min-1)
      (RP) and healthy patients (HP). METHOD: We prospectively included consecutive
      patients aged 18-80 years, with DP (n=37), RP (n=32) and HP (n=48) scheduled for
      distal upper limb surgery. Before surgery, an axillary nerve block (20 mL
      mepivacaine 15 mg.mL-1) was performed with an ultrasound approach combined with
      nerve stimlulation. Five mL was injected for each nerve: median, ulnar, radial,
      musculo-cutaneaous nerves. The primary endpoint measured was the duration of
      sensory block. For statistical analysis, each HP patient was matched with RP and
      DP patient (1:1),with regards to age (range +/- 5 years) and sex. RESULTS:
      Patient characteristics were similar between groups. Creatinine clearance was
      14+/-8 mL.min-1 in RP group and HbA1c (%) was 7.5+/-1.5 in DP group. Mean
      duration of diabetic or renal insufficiencey illness were respectively 8 and 12
      years. Onset time for sensory and motor blocks were similar between groups.
      Average time for sensory block duration was similar between DP vs HP (235 +/- 52
      vs 230 +/- 54 min, p=0.71) ; and between RP vs HP (234 +/- 51 vs 229 +/- 57 min,
      p=0.65). CONCLUSIONS: The short-acting LA (mepivacaine) are associated with
      similar pharmacodynamic effects in diabetic and renal failure patients as
      compared with healthy patients.

PMID- 29589415
TI  - Perioperative hyperglycemia and neurocognitive outcome after surgery: a
      systematic review.
AB  - INTRODUCTION: Preliminary evidence suggest a possible relationship between
      perioperative hyperglycemia, postoperative delirium (POD) or cognitive
      dysfunction (POCD). We aim to present the available clinical evidence related to
      chronic (i.e. diabetes mellitus) or acute perioperative hyperglycemia as risk
      factors for POD/POCD. EVIDENCE ACQUISITION: A literature search of EMBASE (via
      Ovid, 1974-present) online medical database and MEDLINE (via PubMed or Ovid, 1946
      present) was performed. All types of clinical studies including randomized
      controlled trials, prospective, as well as retrospective cohort studies were
      screened. Clinical studies that reported original information on the relationship
      between diabetes mellitus (DM) and/or acute perioperative abnormal glucose levels
      and POD or POCD were selected. Reviews and editorials (i.e. articles not
      presenting original preclinical or clinical research) were excluded and case
      reports were not considered for analysis. EVIDENCE SYNTHESIS: Our search resulted
      in 2356 papers for screening, from which we selected 29 studies that met our
      inclusion criteria. DM was investigated in 24 observational papers, acute
      perioperative hyperglycemia in six observational studies and two randomized
      controlled trials examined the effect of perioperative glucose lowering on
      POD/POCD. Diabetes was associated with POD or POCD in 18/24 observational studies
      and 6/6 of the included observational studies found that perioperative
      hyperglycemia was associated with POD/POCD, independent of diabetes. The two
      randomized controlled trials had a different trial design and reported
      conflicting results. CONCLUSIONS: According to the available evidence, DM and
      acute perioperative hyperglycemia may be associated with an increased risk for
      POD/POCD. These conclusions are based mostly on observational studies and deserve
      more and dedicated research. This systematic review may direct the design of
      future studies.

PMID- 29589416
TI  - Conscious sedation in critically ill patients is associated with stressors
      perception lower than assessed by caregivers.
AB  - BACKGROUND: In ICU, the stay is frequently a stressful experience. Caregivers may
      help to understand patients' perceptions; however, their reliability is
      uncertain. Despite the recent recommendations of lighter sedation targets, little
      is known about the impact of "conscious sedation" on ICU patients memories.
      Purpose of this prospective, observational study is to analyze the stress
      perception in consciously-sedated ICU-patients, comparing it to caregivers and
      staff members. METHODS: Twenty-nine high-risk ICU-patients treated with
      awake/cooperative sedation were enrolled. Before discharge, patients received a
      validated questionnaire for ICU stressors evaluation, also administered to their
      main caregiver (N.=29), to caregivers of other ICU patients not enrolled in the
      study (N.=33) and to staff members (ICU nurses, attending physicians, residents,
      medical students, N.=56). RESULTS: Total stress score was: patients 141+/-41,
      patient relatives 210+/-63, other relatives: 202+/-73, ICU staff: 232+/-44,
      P<0.001. Among patients, older age (P=0.031), longer ICU-stay (P=0.018) and awake
      sedation (P=0.022) were associated with lower stress; sex and illness severity
      had no effect; mechanical ventilation length (P=0.021) and agitation (P=0.029)
      were associated with higher stress. Nurses tended to overestimate stressors more
      than attending physicians and trainees. Within staff members, age (P=0.021) and
      years of experience (P=0.069) were positively associated with overestimation.
      CONCLUSIONS: Conscious sedation is associated with stress perception lower than
      stress assessed by caregivers: relatives and staff members tend to overestimate
      ICU patient stress, more so with increasing age or expertise. A number of
      stressors underestimated by staff and families could be target of specific
      interventions to ameliorate quality of life during ICU stay.

PMID- 29589417
TI  - Blocking around the transversalis fascia: behind the scene.
AB  - BACKGROUND: The transversalis fascia plane and the quadratus lomborum blocks
      target the branches of T12-L1 nerves and provide analgesia in patients undergoing
      surgery involving the corresponding dermatomes. The transversalis fascia is
      believed to contribute to determine the spread of local anesthetic in such
      blocks. Nonetheless, the anatomy of this fascia and its possible role in these
      blocks still have to be precisely defined. METHODS: We conducted a series of 10
      dissections and full-thickness specimens were obtained from one side for the
      microscopic analysis. RESULTS: Macroscopic study showed failed to identify a
      distinguishable fascial structure between the fascia of the transversus abdominis
      muscle and the peritoneum. Microscopic examination showed the presence of a
      further fascial layer (0.1-0.2 mm), ascribable to transversalis fascia.
      Transversalis fascia and transversus abdominis epimysium posteriorly diverge:
      transversus epimysium goes posteriorly to quadratus lomborum to joint the oblique
      internal aponeurosis, while transversalis fascia continues in front to quadratus
      lomborum. So, a little fascial triangle (2-3 mm) is formed on the lateral border
      of quadratus lomborum, defined by transversalis fascia and transversus abdominis.
      Inside this triangle, T12 and L1 nerves are present. CONCLUSIONS: Considering the
      thinness of the transversalis fascia and the small size of the triangular space
      that contains the target nerves, this is most likely a virtual, ideal rather than
      realistic injection site. Accordingly, it is probable that the local anesthetic
      is injected in the much wider retroperitoneal space and reaches the nerves by
      spreading backwards through the thin transversalis fascia.

PMID- 29589418
TI  - Myocardial injury after non-cardiac surgery: a perioperative affair?
AB  - Myocardial injury after non-cardiac surgery (MINS) is a rather new nosological
      entity and an unfortunately common perioperative complication. The diagnostic
      criteria for MINS, also indicated as isolated myocardial injury (IMI), are an
      elevated postoperative high sensitivity troponin T (hsTnT level ranging between
      20 and 65 ng/L with an absolute change of at least 5 ng/L or hsTnT level >65
      ng/L), in absence of symptoms and/or EKG findings suggestive of ischemia and
      without a non-ischemic etiology causing troponin elevation. MINS does not fulfill
      the universal definition of myocardial infarction even if it is related to
      ischemic causes and it is independently associated with 30-day postoperative
      mortality and complications. Nevertheless, mortality at 30 days in MINS patients
      has been calculated up to 10% and it increases exponentially as a function of
      peak postoperative troponin concentration. Physician and researchers should
      discriminate MINS from perioperative myocardial infarction and from not ischemic
      troponin increases. In the postoperative period, the possibility of missing the
      diagnosis of an acute coronary syndrome for the paucity of clinical symptoms or
      because physician failed to evaluate a postoperative EKG recording should always
      be considered. Physiopathology of MINS is not yet well defined: current
      hypotheses are surrogated from perioperative myocardial infarction studies. Up to
      now there are not specific treatments for MINS, even if antithrombotic therapy is
      under evaluation. Treatment decisions should be tailored to the individual case;
      potential benefits of troponin screening include a cardiology consultation and
      consequently, improved patients' information to promote lifestyle changes and
      enhanced therapy.

PMID- 29589419
TI  - Influence of head and neck position on performance of the Ambu(r) AuraGainTM
      laryngeal mask: a randomised crossover study.
AB  - BACKGROUND: The purpose of this study was to investigate the influence of
      different head and neck positions on the performance of the Ambu(r) AuraGainTM, a
      novel laryngeal mask with anatomical curvature. METHODS: Oropharyngeal leak
      pressure, expiratory tidal volume, peak inspiratory pressure, ventilation score,
      and fibreoptic view score through the AuraGainTM were measured in the neutral,
      flexed, and extended neck positions as well as the right rotated head and neck
      position in each patient in a random order. A total of 40 patients were enrolled,
      and data from 39 patients were analysed. RESULTS: Oropharyngeal leak pressure was
      significantly higher in the flexed neck position (32.1+/-7.2 cmH2O, 95% CI of
      mean difference [3.3 to 7.8], P<0.001) and lower in the extended neck position
      (22.0+/-6.8 cmH2O, 95% CI of mean difference [-7.0 to -2.0], P=0.001) compared
      with those in the neutral position (26.6+/-7.5 cmH2O). The ventilation score was
      comparable in all positions. The fibreoptic view score was higher in the extended
      neck position (P<0.001) and right rotated head and neck position (P<0.001)
      compared with that in the neutral position; the vocal cords were most easily
      visualized in the extended neck position. CONCLUSIONS: Head and neck positions
      affect the oropharyngeal seal of the AuraGainTM, as evidenced by the
      oropharyngeal leak pressure, but not enough to impede positive-pressure
      ventilation. Neck flexion can be used when a better oropharyngeal seal is needed,
      and neck extension and right rotation of the head and neck may facilitate
      endotracheal intubation using the AuraGainTM as a conduit.

PMID- 29589420
TI  - Large volume of low concentration of local anesthetic dissolved with low
      molecular weight dextran as adjuvant for ultrasound-guided posterior quadratus
      lumborum block greatly enhances and extends analgesic effects.

PMID- 29589421
TI  - Nasotracheal intubation in ICU: an unfairly forgotten procedure.

PMID- 29589422
TI  - Cannabinoids in chronic pain management: a skein to be untangled.

PMID- 29589423
TI  - Ultrasound-guided bilateral thoracic paravertebral block for emergency incisional
      hernia repair.

PMID- 29589424
TI  - OSA patients: mind them in the preoperative screening!

PMID- 29589425
TI  - Preventing persistent pain after breast cancer surgery: still more work to be
      done.

PMID- 29589426
TI  - Understanding the similarities and distinctions between withholding and
      withdrawing life-sustaining interventions.

PMID- 29589427
TI  - Transmuscular quadratus lumborum block versus serratus-intercostal interfascial
      plane block: the game has just begun.

PMID- 29589428
TI  - Low-molecular weight dextran as adjuvant for ultrasound-guided posterior
      quadratus lumborum block: old things in new ways?

PMID- 29589429
TI  - Core-Sheath Paraffin-Wax-Loaded Nanofibers by Electrospinning for Heat Storage.
AB  - Paraffin wax (PW) is widely used for smart thermoregulation materials due to its
      good thermal performance. However, the leakage and low thermal conductivity of PW
      hinder its application in the heat storage field. Accordingly, developing
      effective methods to address these issues is of great importance. In this study,
      we explored a facile approach to obtain PW-loaded core-sheath structured flexible
      nanofibers films via coaxial electrospinning technique. The PW as the core layer
      was successfully encapsulated by the sheath-layer poly(methyl methacrylate). The
      diameter of the fiber core increased from 395 to 848 nm as the core solution
      speed rate increased from 0.1 to 0.5 mL/h. In addition, it can be seen that
      higher core solution speed rate could lead to higher PW encapsulation efficiency
      according to the transmission electron microscopy results. The core-sheath
      nanofiber films, moreover, possessed the highest latent heat of 58.25 J/g and
      solidifying enthalpy of -56.49 J/g. In addition, we found that after 200 thermal
      cycles, there was little change in latent heat, which demonstrated that it is
      beneficial for the PW-loaded core-sheath structure to overcome the leakage issue
      and enhance thermal stability properties for the thermoregulation film.

PMID- 29589430
TI  - Facile Method and Novel Dielectric Material Using a Nanoparticle-Doped
      Thermoplastic Elastomer Composite Fabric for Triboelectric Nanogenerator
      Applications.
AB  - The trends toward flexible and wearable electronic devices give rise to the
      attention of triboelectric nanogenerators (TENGs) which can gather tiny energy
      from human body motions. However, to accommodate the needs, wearable electronics
      are still facing challenges for choosing a better dielectric material to improve
      their performance and practicability. As a kind of synthetic rubber, the
      thermoplastic elastomer (TPE) contains many advantages such as lightweight, good
      flexibility, high tear strength, and friction resistance, accompanied by good
      adhesion with fabrics, which is an optimal candidate of dielectric materials.
      Herein, a novel nanoparticle (NP)-doped TPE composite fabric-based TENG (TF-TENG)
      has been developed, which operates based on the NP-doped TPE composite fabric
      using a facile coating method. The performances of the TENG device are
      systematically investigated under various thicknesses of TPE films, NP kinds, and
      doping mass. After being composited with a Cu NP-doped TPE film, the TPE
      composite fabric exhibited superior elastic behavior and good bending property,
      along with excellent flexibility. Moreover, a maximum output voltage of 470 V, a
      current of 24 MUA, and a power of 12 mW under 3 MOmega can be achieved by
      applying a force of 60 N on the TF-TENG. More importantly, the TF-TENG can be
      successfully used to harvest biomechanical energy from human body and provides
      much more comfort. In general, the TF-TENG has great application prospects in
      sustainable wearable devices owing to its lightweight, flexibility, and high
      mechanical properties.

PMID- 29589431
TI  - Reconstructing Space- and Energy-Dependent Exciton Generation in Solution
      Processed Inverted Organic Solar Cells.
AB  - Photon absorption-induced exciton generation plays an important role in
      determining the photovoltaic properties of donor/acceptor organic solar cells
      with an inverted architecture. However, the reconstruction of light harvesting
      and thus exciton generation at different locations within organic inverted device
      are still not well resolved. Here, we investigate the film depth-dependent light
      absorption spectra in a small molecule donor/acceptor film. Including depth
      dependent spectra into an optical transfer matrix method allows us to reconstruct
      both film depth- and energy-dependent exciton generation profiles, using which
      short-circuit current and external quantum efficiency of the inverted device are
      simulated and compared with the experimental measurements. The film depth
      dependent spectroscopy, from which we are able to simultaneously reconstruct
      light harvesting profile, depth-dependent composition distribution, and vertical
      energy level variations, provides insights into photovoltaic process. In
      combination with appropriate material processing methods and device architecture,
      the method proposed in this work will help optimizing film depth-dependent
      optical/electronic properties for high-performance solar cells.

PMID- 29589432
TI  - High-Performance Organic Photodetectors from a High-Bandgap Indacenodithiophene
      Based pi-Conjugated Donor-Acceptor Polymer.
AB  - A conjugated donor-acceptor polymer, poly[4,4,9,9-tetrakis(4-hexylphenyl)-4,9
      dihydro- s-indaceno[1,2- b:5,6- b']dithiophene-2,7-diyl- alt-5-(2-ethylhexyl)-4 H
      thieno[3,4- c]pyrrole-4,6(5 H)-dione-1,3-diyl] (PIDT-TPD), is blended with the
      fullerene derivative [6,6]phenyl-C61-butyric acid methyl ester (PC61BM) for the
      fabrication of thin and solution-processed organic photodetectors (OPDs).
      Systematic screening of the concentration ratio of the blend and the molecular
      weight of the polymer is performed to optimize the active layer morphology and
      the OPD performance. The device comprising a medium molecular weight polymer
      (27.0 kg/mol) in a PIDT-TPD:PC61BM 1:1 ratio exhibits an external quantum
      efficiency of 52% at 610 nm, a dark current density of 1 nA/cm2, a detectivity of
      1.44 * 1013 Jones, and a maximum 3 dB cutoff frequency of 100 kHz at -5 V bias.
      These results are remarkable among the state-of-the-art red photodetectors based
      on conjugated polymers. As such, this work presents a functional organic active
      material for high-speed OPDs with a linear photoresponse at different light
      intensities.

PMID- 29589433
TI  - Sensitivity-Tunable Colorimetric Detection of Chloropicrin Vapor on Nylon-6
      Nanofibrous Membrane Based on a Detoxification Reaction with Biological Thiols.
AB  - Detoxification reaction of chloropicrin in the human body with biological thiols
      was selected for detection of chloropicrin in the air. The consumption of free
      sulfhydryl group in biological thiols by chloropicrin is colorimetrically
      detectable with the addition of the Ellman's reagent. In this study, glutathione,
      N-acetyl-l-cysteine, l-homocysteine, cysteamine, and thioglycolic acid were
      tested as sensing agents for chloropicrin vapor detection in ppb concentration
      range. The reactivity of the selected biological thiols was investigated based on
      both their redox properties and the nucleophilic strength of the sulfhydryl
      groups. Nylon-6 nanofibrous membrane and an organic solvent were used as a sensor
      matrix and a vapor sorbent, respectively, to provide solid supports with
      ultrahigh surface area and enhanced adsorption to chloropicrin vapor. The tunable
      sensitivity and detection range by using different biological thiols was achieved
      on the sensors due to the different reactivity of thiols toward chloropicrin.

PMID- 29589434
TI  - Enhancement in Open-Circuit Voltage in Organic Solar Cells by Using Ladder-Type
      Nonfullerene Acceptors.
AB  - The open-circuit voltage ( Voc) loss has always been a major factor in lowering
      power conversion efficiencies (PCEs) in bulk heterojunction organic photovoltaic
      cells (OPVs). A method to improve the Voc is indispensable to achieve high PCEs.
      In this paper, we investigated a series of perylene diimide-based ladder-type
      molecules as electron acceptors in nonfullerene OPVs. The D-A ladder-type
      structures described here lock our pi-systems into a planar structure and
      eliminate bond twisting associated with linear conjugated systems. This enlarges
      the interface energy gap (Delta EDA), extends electronic delocalization, and
      hence improves the Voc. More importantly, these devices showed an increase in Voc
      without compromising either the Jsc or the FF. C5r exhibited a strong
      intermolecular interaction and a PCE value of 6.1%. Moreover, grazing-incident
      wide-angle X-ray scattering analysis and atomic force microscopy images suggested
      that our fused-ring acceptors showed a suitable domain size and uniform blend
      films, which were not affected by their rigid molecular structures.

PMID- 29589435
TI  - Determination of Gold Ions in Human Urine Using Genetically Engineered
      Microorganisms on a Paper Device.
AB  - This paper presents a whole-cell biosensor that operates in conjunction with a
      smartphone-based fluorescence diagnostic system on a paper device to monitor the
      concentration of gold ions in human urine. The heavy metal-tolerant bacteria
      Cupriavidus metallidurans was genetically engineered for use as a chassis in a
      red fluorescent protein (RFP)-based microbial sensor. The biosensor is highly
      sensitive to gold ions, with a detection limit of 110 nM. The proposed smartphone
      based analysis system provides a user-friendly approach to design tools of
      personal health monitoring for reporting the presence of gold ions in human
      urine.

PMID- 29589436
TI  - Biotoxin Tropolone Contamination Associated with Nationwide Occurrence of
      Pathogen Burkholderia plantarii in Agricultural Environments in China.
AB  - Tropolone, a biotoxin produced by the agricultural pathogen Burkholderia
      plantarii, exerts cytotoxicity toward a wide array of biota. However, due to the
      lack of quantitative and qualitative approach, both B. plantarii occurrence and
      tropolone contamination in agricultural environments remain poorly understood.
      Here, we presented a sensitive and reliable method for detection of B. plantarii
      in artificial, plant, and environmental matrices by tropolone-targeted gas
      chromatography-triple-quadrupole tandem mass spectrometry analysis. Limits of
      detection for B. plantarii and tropolone were 10 colony-forming units (CFU)/mL
      and 0.017 MUg/kg, respectively. In a series of simulation trials, we found that
      B. plantarii from 10 to 108 CFU/mL produced tropolone between 0.006 and 107.8
      mg/kg in a cell-population-dependent manner, regardless of habitat. Correlation
      analysis clarified a reliable reflection of B. plantarii density by tropolone
      level with R2 values from 0.9201 to 0.9756 ( p < 0.01). Through a nationwide
      pilot study conducted in China, tropolone contamination was observed at 0.014
      0.157 mg/kg in paddy soil and rice grains, and subsequent redundancy analysis
      revealed soil organic matter to be a dominant environmental factor, having a
      positive correlation with tropolone contamination. In this context, our results
      imply that potential ecological and dietary risks posed by long-term exposure to
      trace levels of tropolone contamination are of concern.

PMID- 29589437
TI  - Atomic-Scale Simulation of Electrochemical Processes at Electrode/Water
      Interfaces under Referenced Bias Potential.
AB  - Based on constant Fermi-level molecular dynamics and a proper alignment scheme,
      we perform simulations of the Pt(111)/water interface under variable bias
      potential referenced to the standard hydrogen electrode (SHE). Our scheme yields
      a potential of zero charge MUpzc of ~0.22 eV relative to the SHE and a double
      layer capacitance Cdl of ?19 MUF cm-2, in excellent agreement with experimental
      measurements. In addition, we study the structural reorganization of the
      electrical double layer for bias potentials ranging from -0.92 eV to +0.44 eV and
      find that Odown configurations, which are dominant at potentials above the pzc,
      reorient to favor Hdown configurations as the measured potential becomes
      negative. Our modeling scheme allows one to not only access atomic-scale
      processes at metal/water interfaces, but also to quantitatively estimate
      macroscopic electrochemical quantities.

PMID- 29589438
TI  - Waterproof and Tailorable Elastic Rechargeable Yarn Zinc Ion Batteries by a Cross
      Linked Polyacrylamide Electrolyte.
AB  - Emerging research toward next-generation flexible and wearable electronics has
      stimulated the efforts to build highly wearable, durable, and deformable energy
      devices with excellent electrochemical performances. Here, we develop a high
      performance, waterproof, tailorable, and stretchable yarn zinc ion battery (ZIB)
      using double-helix yarn electrodes and a cross-linked polyacrylamide (PAM)
      electrolyte. Due to the high ionic conductivity of the PAM electrolyte and helix
      structured electrodes, the yarn ZIB delivers a high specific capacity and
      volumetric energy density (302.1 mAh g-1 and 53.8 mWh cm-3, respectively) as well
      as excellent cycling stability (98.5% capacity retention after 500 cycles). More
      importantly, the quasi-solid-state yarn ZIB also demonstrates superior
      knittability, good stretchability (up to 300% strain), and superior waterproof
      capability (high capacity retention of 96.5% after 12 h underwater operation). In
      addition, the long yarn ZIB can be tailored into short ones, and each part still
      functions well. Owing to its weavable and tailorable nature, a 1.1 m long yarn
      ZIB was cut into eight parts and woven into a textile that was used to power a
      long flexible belt embedded with 100 LEDs and a 100 cm2 flexible
      electroluminescent panel.

PMID- 29589439
TI  - Cost, Energy, and Environmental Impact of Automated Electric Taxi Fleets in
      Manhattan.
AB  - Shared automated electric vehicles (SAEVs) hold great promise for improving
      transportation access in urban centers while drastically reducing transportation
      related energy consumption and air pollution. Using taxi-trip data from New York
      City, we develop an agent-based model to predict the battery range and charging
      infrastructure requirements of a fleet of SAEVs operating on Manhattan Island. We
      also develop a model to estimate the cost and environmental impact of providing
      service and perform extensive sensitivity analysis to test the robustness of our
      predictions. We estimate that costs will be lowest with a battery range of 50-90
      mi, with either 66 chargers per square mile, rated at 11 kW or 44 chargers per
      square mile, rated at 22 kW. We estimate that the cost of service provided by
      such an SAEV fleet will be $0.29-$0.61 per revenue mile, an order of magnitude
      lower than the cost of service of present-day Manhattan taxis and $0.05-$0.08/mi
      lower than that of an automated fleet composed of any currently available hybrid
      or internal combustion engine vehicle (ICEV). We estimate that such an SAEV fleet
      drawing power from the current NYC power grid would reduce GHG emissions by 73%
      and energy consumption by 58% compared to an automated fleet of ICEVs.

PMID- 29589440
TI  - Suppression of Auger Recombination in Nanocrystals via Ligand-Assisted Wave
      Function Engineering in Reciprocal Space.
AB  - A limiting factor to the technological application of conventional semiconductor
      nanostructures is their fast Auger recombination time. Strategies to increase it
      have so far mostly focused on decreasing the electron-hole wave function overlap
      in real space through structural modifications involving either elongation or
      shell growth. Here we propose an alternative mechanism for Auger recombination
      suppression: a decrease in the overlap of electron and hole wave functions in
      reciprocal space.

PMID- 29589441
TI  - Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and
      Antirheumatic Histone Deacetylase 6 Inhibitors.
AB  - Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to
      autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence,
      histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene
      expression patterns, and cell fate decisions, represent promising new drugs for
      the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent
      histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific
      inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side
      effects. We present the synthesis and biological evaluation of Marbostats, novel
      HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-beta
      carboline derivatives. Our lead compound Marbostat-100 is a more potent and more
      selective HDAC6i than previously established well-characterized compounds in
      vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and
      effective against collagen type II induced arthritis. Thus, Marbostat-100
      represents a most selective known HDAC6i and the possibility for clinical
      evaluation of a HDAC isoform-specific drug.

PMID- 29589442
TI  - Iodine-Catalyzed C-H Amidation and Imination at the 2alpha-Position of 2,3
      Disubstituted Indoles with Chloramine Salts.
AB  - A novel iodine-catalyzed amidation and imination at the 2alpha-position of 2,3
      disubstituted indoles in the presence of chloramine salts with high
      regioselectivity has been achieved. The protocol is applicable to a wide range of
      substrates to deliver the corresponding 2alpha-nitrogen-containing indole
      derivatives. Furthermore, to demonstrate the synthetic value of this established
      transformation, a concise assembly of the bridged tetracyclic framework of
      akuammiline alkaloids from the 2alpha-amidated product has been accomplished in
      five steps.

PMID- 29589443
TI  - Nanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea
      Transporter UT-A1.
AB  - Urea transporter A (UT-A) isoforms encoded by the Slc14a2 gene are expressed in
      kidney tubule epithelial cells, where they facilitate urinary concentration. UT
      A1 inhibition is predicted to produce a unique salt-sparing diuretic action in
      edema and hyponatremia. Here we report the discovery of 1,2,4
      triazoloquinoxalines and the analysis of 37 synthesized analogues. The most
      potent compound, 8ay, containing 1,2,4-triazolo[4,3- a]quinoxaline-substituted
      benzenesulfonamide linked by an aryl ether, rapidly and reversibly inhibited UT
      A1 urea transport by a noncompetitive mechanism with IC50 ~ 150 nM; the IC50 was
      ~2 MUM for the related urea transporter UT-B encoded by the Slc14a1 gene.
      Molecular modeling suggested a putative binding site on the UT-A1 cytoplasmic
      domain. In vitro metabolism showing quinoxaline ring oxidation prompted the
      synthesis of metabolically stable 7,8-difluoroquinoxaline analogue 8bl, which
      when administered to rats produced marked diuresis and reduced urinary
      osmolality. 8bl has substantially improved UT-A1 inhibition potency and metabolic
      stability compared with prior compounds.

PMID- 29589444
TI  - Actinium Hydrides AcH10, AcH12, and AcH16 as High-Temperature Conventional
      Superconductors.
AB  - The stability of numerous unexpected actinium hydrides was predicted via the
      evolutionary algorithm USPEX. The electron-phonon interaction was investigated
      for the hydrogen-richest and most symmetric phases: R3 m-AcH10, I4/ mmm-AcH12,
      and P6 m2-AcH16. Predicted structures of actinium hydrides are consistent with
      all previously studied Ac-H phases and demonstrate phonon-mediated high
      temperature superconductivity with TC in the range of 204-251 K for R3 m-AcH10 at
      200 GPa and 199-241 K for P6 m2-AcH16 at 150 GPa, which was estimated by directly
      solving the Eliashberg equation. Actinium belongs to the series of d1 elements
      (Sc-Y-La-Ac) that form high- TC superconducting (HTSC) hydrides. Combining this
      observation with previous predictions of p0-HTSC hydrides (MgH6 and CaH6), we
      propose that p0 and d1 metals with low-lying empty orbitals tend to form phonon
      mediated HTSC metal polyhydrides.

PMID- 29589445
TI  - 1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1)
      as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands
      with High Affinity and Selectivity for Dopamine D4 Receptor.
AB  - In the present article, the M1 mAChR bitopic agonist 1-[3-(4-butylpiperidin-1
      yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 1) has been demonstrated
      to show unexpected D4R selectivity over D2R and D3R and to behave as a D4R
      antagonist. To better understand the structural features required for the
      selective interaction with the D4R and to obtain compounds unable to activate
      mAChRs, the aliphatic butyl chain and the piperidine nucleus of 1 were modified,
      affording compounds 2-14. The 4-benzylpiperidine 9 and the 4-phenylpiperazine 12
      showed high D4R affinity and selectivity not only over the other D2-like
      subtypes, but also over M1-M5 mAChRs. Derivative 12 was also highly selective
      over some selected off-targets. This compound showed biased behavior, potently
      and partially activating Gi protein and inhibiting beta-arrestin2 recruitment in
      functional studies. Pharmacokinetic studies demonstrated that it was
      characterized by a relevant brain penetration. Therefore, 12 might be a useful
      tool to better clarify the role played by D4R in disorders in which this subtype
      is involved.

PMID- 29589446
TI  - Longitudinal Monitoring of Biofilm Formation via Robust Surface-Enhanced Raman
      Scattering Quantification of Pseudomonas aeruginosa-Produced Metabolites.
AB  - Detection of bacterial metabolites at low concentrations in fluids with complex
      background allows for applications ranging from detecting biomarkers of
      respiratory infections to identifying contaminated medical instruments. Surface
      enhanced Raman scattering (SERS) spectroscopy, when utilizing plasmonic nanogaps,
      has the relatively unique capacity to reach trace molecular detection limits in a
      label-free format, yet large-area device fabrication incorporating nanogaps with
      this level of performance has proven difficult. Here, we demonstrate the
      advantages of using chemical assembly to fabricate SERS surfaces with controlled
      nanometer gap spacings between plasmonic nanospheres. Control of nanogap spacings
      via the length of the chemical crosslinker provides uniform SERS signals,
      exhibiting detection of pyocyanin, a secondary metabolite of Pseudomonas
      aeruginosa, in aqueous media at concentration of 100 pg.mL-1. When using machine
      learning algorithms to analyze the SERS data of the conditioned medium from a
      bacterial culture, having a more complex background, we achieve 1 ng.mL-1 limit
      of detection of pyocyanin and robust quantification of concentration spanning 5
      orders of magnitude. Nanogaps are also incorporated in an in-line microfluidic
      device, enabling longitudinal monitoring of P. aeruginosa biofilm formation via
      rapid pyocyanin detection in a medium effluent as early as 3 h after inoculation
      and quantification in under 9 h. Surface-attached bacteria exposed to a
      bactericidal antibiotic were differentially less susceptible after 10 h of
      growth, indicating that these devices may be useful for early intervention of
      bacterial infections.

PMID- 29589447
TI  - Prototypical Organic-Oxide Interface: Intramolecular Resolution of Sexiphenyl on
      In2O3(111).
AB  - The performance of an organic semiconductor device is critically determined by
      the geometric alignment, orientation, and ordering of the organic molecules.
      Although an organic multilayer eventually adopts the crystal structure of the
      organic material, the alignment and configuration at the interface with the
      substrate/electrode material are essential for charge injection into the organic
      layer. This work focuses on the prototypical organic semiconductor para
      sexiphenyl (6P) adsorbed on In2O3(111), the thermodynamically most stable surface
      of the material that the most common transparent conducting oxide, indium tin
      oxide, is based on. The onset of nucleation and formation of the first monolayer
      are followed with atomically resolved scanning tunneling microscopy and
      noncontact atomic force microscopy (nc-AFM). Annealing to 200  degrees C provides
      sufficient thermal energy for the molecules to orient themselves along the high
      symmetry directions of the surface, leading to a single adsorption site. The AFM
      data suggests an essentially planar adsorption geometry. With increasing
      coverage, the 6P molecules first form a loose network with a poor long-range
      order. Eventually, the molecules reorient into an ordered monolayer. This first
      monolayer has a densely packed, well-ordered (2 * 1) structure with one 6P per
      In2O3(111) substrate unit cell, that is, a molecular density of 5.64 * 1013 cm-2.

PMID- 29589448
TI  - Seeing Multiexcitons through Sample Inhomogeneity: Band-Edge Biexciton Structure
      in CdSe Nanocrystals Revealed by Two-Dimensional Electronic Spectroscopy.
AB  - The electronic structure of multiexcitons significantly impacts the performance
      of nanostructures in lasing and light-emitting applications. However, these
      multiexcitons remain poorly understood due to their complexity arising from many
      body physics. Standard transient-absorption and photoluminescence spectroscopies
      are unable to unambiguously distinguish effects of sample inhomogeneity from
      exciton-biexciton interactions. Here, we exploit the energy and time resolution
      of two-dimensional electronic spectroscopy to access the electronic structure of
      the band-edge biexciton in colloidal CdSe quantum dots. By removing effects of
      inhomogeneities, we show that the band-edge biexciton structure must consist of a
      discrete manifold of electronic states. Furthermore, the biexciton states within
      the manifold feature distinctive binding energies. Our findings have direct
      implications for optical gain thresholds and efficiency droop in light-emitting
      devices and provide experimental measures of many-body physics in nanostructures.

PMID- 29589449
TI  - Improving Quantum Yield of Upconverting Nanoparticles in Aqueous Media via
      Emission Sensitization.
AB  - We demonstrate a facile method to improve upconversion quantum yields in Yb,Er
      based nanoparticles via emission dye-sensitization. Using the commercially
      available dye ATTO 542, chosen for its high radiative rate and significant
      spectral overlap with the green emission of Er3+, we decorate the surfaces of sub
      25 nm hexagonal-phase Na(Y/Gd/Lu)0.8F4:Yb0.18Er0.02 upconverting nanoparticles
      with varying dye concentrations. Upconversion photoluminescence and absorption
      spectroscopy provide experimental confirmation of energy transfer to and emission
      from the dye molecules. Upconversion quantum yield is observed to increase with
      dye sensitization, with the highest enhancement measured for the smallest
      particles investigated (10.9 nm in diameter); specifically, these dye-decorated
      particles are more than 2* brighter than are unmodified, organic-soluble
      nanoparticles and more than 10* brighter than are water-soluble nanoparticles. We
      also observe 3* lifetime reductions with dye adsorption, confirming the quantum
      yield enhancement to result from the high radiative rate of the dye. The approach
      detailed in this work is widely implementable, renders the nanoparticles water
      soluble, and most significantly improves sub-15 nm nanoparticles, making our
      method especially attractive for biological imaging applications.

PMID- 29589450
TI  - Spiro-Conjugated Molecular Junctions: Between Jahn-Teller Distortion and
      Destructive Quantum Interference.
AB  - The quest for molecular structures exhibiting strong quantum interference effects
      in the transport setting has long been on the forefront of chemical research. We
      establish theoretically that the unusual geometry of spiro-conjugated systems
      gives rise to complete destructive interference in the resonant-transport regime.
      This results in a current blockade of the type not present in meta-connected
      benzene or similar molecular structures. We further show that these systems can
      undergo a transport-driven Jahn-Teller distortion, which can lift the
      aforementioned destructive-interference effects. The overall transport
      characteristics are determined by the interplay between the two phenomena. Spiro
      conjugated systems may therefore serve as a novel platform for investigations of
      quantum interference and vibronic effects in the charge-transport setting. The
      potential to control quantum interference in these systems can also turn them
      into attractive components in designing functional molecular circuits.

PMID- 29589452
TI  - [Prediction of bowel damage in patients with gastroschisis].
AB  - INTRODUCTION: Gastroschisis is the most common malformation among abdominal wall
      defects with the incidence of 1:45000 live birth neonates. Postoperative care for
      these patients is very difficult due to the risk of abdominal compartment
      syndrome. The identification of markers that correlate with bowel damage in
      gastroschisis may prevent this serious postoperative complication. METHODS:
      Review of the literature. CONCLUSION: Prenatal ultrasound prediction of bowel
      damage followed by an appropriate surgical strategy is a possibility of
      optimizing care and outcomes in gastroschisis patients. The dynamics of I-FABP is
      a promising biomarker for the elimination of abdominal compartment syndrome
      during postoperative care.Key words: gastroschisis preformed silo intraabdominal
      dilatation I-FABP.

PMID- 29589451
TI  - Reliable Strategy for Analysis of Complex Biosensor Data.
AB  - When using biosensors, analyte biomolecules of several different concentrations
      are percolated over a chip with immobilized ligand molecules that form complexes
      with analytes. However, in many cases of biological interest, e.g., in antibody
      interactions, complex formation steady-state is not reached. The data measured
      are so-called sensorgram, one for each analyte concentration, with total complex
      concentration vs time. Here we present a new four-step strategy for more reliable
      processing of this complex kinetic binding data and compare it with the standard
      global fitting procedure. In our strategy, we first calculate a dissociation
      graph to reveal if there are any heterogeneous interactions. Thereafter, a new
      numerical algorithm, AIDA, is used to get the number of different complex
      formation reactions for each analyte concentration level. This information is
      then used to estimate the corresponding complex formation rate constants by
      fitting to the measured sensorgram one by one. Finally, all estimated rate
      constants are plotted and clustered, where each cluster represents a complex
      formation. Synthetic and experimental data obtained from three different QCM
      biosensor experimental systems having fast (close to steady-state), moderate, and
      slow kinetics (far from steady-state) were evaluated using the four-step strategy
      and standard global fitting. The new strategy allowed us to more reliably
      estimate the number of different complex formations, especially for cases of
      complex and slow dissociation kinetics. Moreover, the new strategy proved to be
      more robust as it enables one to handle system drift, i.e., data from biosensor
      chips that deteriorate over time.

PMID- 29589453
TI  - [Multidisciplinary approach to surgical disorders of the pancreas in children].
AB  - INTRODUCTION: Surgical diseases of the pancreas in children are not common and
      may be associated with significant morbidity and potential mortality. A
      multidisciplinary approach is essential for correct diagnosis, surgical strategy
      and postoperative as well as follow-up care. METHOD: Retrospective analysis of
      patients operated on due to a pathological lesion of the pancreas focused on
      diagnostics, operating procedures, postoperative complications, and long-term
      results. Between 1991 and 2016, eighty-nine children were treated in our
      department for a pathologic lesion of the pancreas. 39 of them were boys and 50
      were girls. RESULTS: Mean age of the patients was 9.3 years (1 month-18.4 years).
      Patients were followed from the operation to the age of 19, after which they were
      referred for follow-up to adult specialists. The indications for surgery were
      trauma in 34 children, solid pseudopapillary tumor in 23 children, biopsy in 10,
      hyperinsulinism in 8, chronic pancreatitis in 4, pancreatic cyst in 3, insulinoma
      in 3, carcinoma in 2, and serous cystadenoma and pancreas divisum in one patient.
      The most frequent procedures performed on the pancreas were distal pancreatectomy
      in 35 cases, the duodenum-preserving pancreatic head resection in 23 cases,
      pseudocystogastroanastomosis in 11 cases, 9095% pancreatic resection in 5 cases,
      Whipple operation in two cases, Puestow procedure in one case, tumor enucleation
      in one case, and tumor biopsy for cancer in one case. In 5 patients after major
      pancreatic injury, ERCP and papillotomy with insertion of a stent into the
      pancreatic duct was performed. 3 patients died, one after a polytrauma with
      severe pancreatic injury and two patients with pancreatic cancer. CONCLUSION:
      Pancreatic surgery in children is not a common operation, and individual as well
      as institutional experience remains limited. After more than 20 years of
      experience with pancreatic surgery, we believe that close cooperation with
      surgeons, pediatric gastroenterologists, radiologists, anesthesiologists,
      intensivist, pathologists and ERCP specialists is necessary for successful
      diagnosis and treatment of pancreatic disease in children.Key words: pancreas
      pancreatic surgery in children duodenum preserving head resection of the
      pancreas.

PMID- 29589454
TI  - [Open versus laparoscopic appendectomy for acute appendicitis in children].
AB  - INTRODUCTION: Acute appendicitis is a common disease affecting both adults and
      children. The basic therapeutic procedure is an appendectomy. Open appendectomy
      has been gradually supplemented and sometimes replaced by a laparoscopic approach
      in numerous departments. The aim of our work was to compare laparoscopic and open
      surgery objectively. METHOD: Retrospective analysis of data from patients
      operated on at the Department of Pediatric Surgery and Traumatology, Teaching
      Hospital in Hradec Kralove in 20092016. Only the precisely evaluated parameters,
      i.e. the time of anesthesia, the time of surgery and the duration of post
      operative pain, were assessed within the scope of objectification. Data were
      evaluated only in a homogeneous group of patients with phlegmonous appendicitis.
      RESULTS: During the above period, 261 patients with acute appendicitis were
      operated on at our department, 166 of whom suffered from phlegmonous
      appendicitis. 133 children were operated laparoscopically and 33 by open
      procedure. The results obtained were statistically significantly different only
      for the time of anesthesia (p=0.00035) which was shorter in open operations. The
      time of surgery was also shorter in the open operation group, but only at the
      limit of statistical significance. A statistically significant difference was not
      found in the time of duration of pain for individual surgical approaches.
      CONCLUSION: Laparoscopic approach in the surgical treatment of acute appendicitis
      is a more modern method than open surgery and it has become a standard procedure
      in some departments. However, the results of our study confirm that the open
      approach remains an equivalent alternative to the treatment of acute phlegmonous
      appendicitis.Key words: appendicitis open appendectomy laparoscopy.

PMID- 29589455
TI  - [Supracondylar fracture of the humerus in childhood].
AB  - INTRODUCTION: Supracondylar fracture of the humerus can be considered the most
      serious fracture in childhood. Problems with its diagnostics and treatment as
      well as its complications and sequels have not been fully solved yet. That is
      evidenced by a large amount of articles with frequently inconsistent conclusions.
      The aim is to evaluate contemporary diagnostic and therapeutic approach based on
      our own clinical experience. METHODS: A total of 2847 children with skeletal
      injury were treated by the authors during the year 2016. Two hundred and seventy
      five of them suffered from supracondylar fracture of the humerus (9.66%). All the
      fractures were classified using the authors own scheme. Fragment displacement was
      evaluated according to a three-degree scale. RESULTS: Ninety-three of 275
      supracondylar fractures were treated non-operatively (33.8%) and 182 by surgery
      (66.2%). Closed reduction and percutaneous pinning by K-wires under X-ray (C-arm)
      control was the method of choice. Crossed K-wires were used in 90% and in 9.9%
      two K-wires were inserted laterally only. In 70.9%, pins were buried and in 29.1
      % unburied pins were used. Neurological lesions were noted in 13.5%. A total of
      82.9% of children were healed without any sequels. CONCLUSION: Supracondylar
      fracture of the humerus in children should be managed in pediatric trauma
      centers, especially in more complicated cases. Fracture classification needs to
      be more detailed than those commonly used so far. Closed reduction and
      percutaneous pinning is the method of choice. Acute neurological and/or vascular
      complications can be managed in an overwhelming majority of cases, after fragment
      fixation, non-surgically.Key words: supracondylar fracture humerus, miniinvasive
      osteosynthesis neural lesion compartment syndrome.

PMID- 29589456
TI  - [Laparoscopy at the pediatric surgery department for a five-year period].
AB  - INTRODUCTION: Laparoscopy in small children was developed only after the adoption
      and verification of basic principles in adult patients and is mostly concentrated
      in specialized facilities due to the possible complications and necessity of
      follow-up specialized anesthesiological and post-operative care. In the 1990s,
      the Clinic of Paediatric Surgery, Orthopaedics and Traumatology at University
      Hospital Brno was one of the first in the Czech Republic to begin operating on
      children laparoscopically. The presented study informs about the development of
      these minimally invasive methods, the frequency of their use, and the spectrum of
      patients at the pediatric surgery facility where laparoscopy in children has been
      systematically developed over many years. METHODS: Retrospective analysis of
      children operated upon laparoscopically at the clinic of Paediatric surgery,
      Orthopaedics and Traumatology of University Hospital Brno over the five-year
      period from 1 January 2012 to 31 December 2016. A list of surgical procedures was
      prepared which was then first divided into procedures specific exclusively for
      children and those common to adult patients surgery. Separately, an overview was
      prepared of operated patients under 50 kg, which was the boundary criterion
      defined by the authors for laparoscopy in children as opposed to adults. For all
      procedures, the frequency of the completed cases performed laparoscopically was
      precisely ascertained. The source for this data was the hospital system and
      surgical documentation. RESULTS: In the evaluated period, a total of 995
      laparoscopic procedures were performed, more than half of which (56.8%) were in
      patients under 50 kg. The majority of those were procedures performed also in
      adults. The group of surgical operations exclusively specific to children was
      characterized by low frequencies of the individual procedures. CONCLUSION: The
      presented analysis confirms that laparoscopy in children is based on standard
      procedures common to surgery on adults. These procedures are adopted the most
      quickly, and they can be disseminated across a large group of surgeons who are
      then able to perform these routinely on child patients. Surgical procedures
      exclusively specific for children, on the other hand, are performed less
      frequently, their adoption is slower, and laparoscopic approach is less common.
      Therefore, laparoscopy specific to children needs to be performed on a long-term
      basis, systematically, and within a small group of surgeons. Otherwise, it is
      better not to perform it at all.Key words: laparoscopy - child frequency.

PMID- 29589457
TI  - [Hirschsprungs disease in adults two case reports and review of the literature].
AB  - Hirschsprungs disease (HD) in adults is extremely rare, only three publications
      in Czech and Czechoslovak journals making reference to the condition after
      childhood. We present two cases of adult patients with HD. The first case is a 46
      year-old male patient suffering from chronic constipation since childhood and
      diagnosed with megacolon at the age of 16; however, no further detailed diagnosis
      was done. At the age of 41, he developed a sigmoid perforation due to fecaloma
      and underwent urgent rectosigmoid resection and colostomy. 5 months later,
      Swensons coloanal anastomosis with diverting ileostomy was performed.
      Postoperative course was uneventful. He has two bowel movements a day. 7 years
      after the Swensons procedure, he also underwent adhesiolysis for acute bowel
      obstruction. His daughter was operated on due to HD at 16 days of age. The second
      case is a 57-year-old male patient. He suffered from chronic constipation and
      megacolon since 2 years of age and was diagnosed with congenital megacolon at the
      age of 19. However, no detailed diagnostics followed. He had a long interval
      between stools of up to 14 days. He underwent colonoscopy and, with a diagnosis
      of resistant Crohns disease, was referred to a surgical department where he was
      diagnosed with HD. Left hemicolectomy was first performed, followed by Swensons
      procedure with diverting ileostomy. All postoperative courses were uneventful.
      Currently he passes one or two soft stools a day. Adult HD is extremely rare.
      However, adult surgeons should consider it in case of refractory constipation
      since childhood associated with megacolon. Diagnosis is based on contrast
      radiography and rectal biopsy. Both Swensons and Duhamels procedures are suitable
      for surgical management. Left hemicolectomy with colonic rotation and coloanal
      anastomosis and/or proctocolectomy with J-pouch anastomosis are indicated in
      advanced forms of non-functional megacolon.Key words: adult Hirschsprungs disease
      - megacolon surgical therapy.

PMID- 29589458
TI  - Laparoscopic treatment of bowel perforation after blunt abdominal trauma (BAT) in
      children.
AB  - Minimally invasive techniques have now become standard for the treatment of many
      surgical conditions in children. There are a few studies that describe the
      utility of laparoscopy in BAT in children. In this article, we describe the
      complete laparoscopic surgical treatment of two patients after a single blunt
      abdominal trauma, both with bowel perforation. In both cases, the perforation was
      identified and closed, one laparoscopically with an ongoing suture, the second
      jejune perforation was closed by laparoscopic-assisted techniques. Both patients
      had an uneventful postoperative recovery. Therapeutic laparoscopic treatment of
      patients with upper gastrointestinal perforation is feasible. We hypothesize,
      that diagnostic laparoscopy provides important information for the treatment of
      children with abdominal trauma and is accompanied by improved diagnostic
      accuracy, reduction of nontherapeutic laparotomy rates, and a reduction of
      morbidity. Minimally invasive surgery in children after BAT is suitable for
      hemodynamic stable patients, could improve pain scores, cosmetic effect, shorter
      hospital stays, shorter operative times and shorter return to school/activities.
      However, at any point in the patients care, in case the unstable hemodynamic is
      encountered, exploratory laparotomy is the procedure of choice.Key words:
      miniinvasive surgery blunt abdominal trauma - laparoscopy bowel perforation.

PMID- 29589459
TI  - [The Uncorrected Near Visual Acuity after the Monofocal Intraocular Lens
      Implantation].
AB  - Aim of the study was to evaluate retrospectively selected parameters, which
      influence the postoperative near visual acuity in a group of pseudophakic eyes of
      patients with Uncorrected Distance Visual Acuity (UDVA) and according to acquired
      results establish those, which mostly influenced good Uncorrected Near Visual
      Acuity (UNVA) after the implantation of monofocal IntraOcular Lens (IOL).
      Altogether, 122 pseudophakic eyes of 65patients were followed up, out of them in
      57 patients both eyes were operated on. The frequency of visual acuity for three
      groups of operated eyes categorized according to the crucial parameter - eyes
      axial length (short, average, long) was evaluated. In each of groups, the average
      parameters (age, axial length, keratometry, and depth of the anterior chamber)
      were established, as well as relative frequency of postoperative uncorrected near
      visual acuity on conventionally used reading tables. The near visual acuity
      assessment for each eye separately was preformed in its horizontal position using
      the Zeiss table. The study did not confirm positive correlation of postoperative
      near visual acuity on the age of the patient, depth of the anterior chamber, nor
      the implanted IOL type. It was confirmed the presumption of optimal near visual
      acuity for eyes with axial length shorter than 23.5 mm, and in the process,
      between both parameters slightly negative correlation was found. On the other
      hand, middle positive correlation between uncorrected near visual acuity and
      central corneal power (in dioptres) in eyes with the axial length 22.5 - 23.5 mm
      was found. The study confirmed, that higher values of the central corneal power
      (in dioptres) and the high borderline value of the axial length up to 23.5 mm are
      the condition for optimal postoperative uncorrected near visual acuity after the
      implantation of monofocal intraocular lens.Key words: Uncorrected Near Visual
      Acuity (UNVA), monofocal intraocular lens, pseudoaccommodation.

PMID- 29589460
TI  - [Treatment of Keratoconus by Accelerated Cross-linking].
AB  - This study evaluates the efficacy of treatment of progressive keratoconus using
      Accelerated Corneal Collagen cross-linking (ACXL) method. Patients underwent ACXL
      at the Dept. of Ophthalmology of University Hospital in Hradec Kralove between
      2012 - 2013. Uncorrected distance visual acuity, best corrected distance visual
      acuity, keratometry (K1, K2, Kmax), corneal astigmatism and corneal pachymetry
      were measured preoperatively and in 6 months, 1year, 2 and 3 years after the
      surgery. The results were statistically analysed by non-parametric Wilcoxon test.
      There were found statistically significant changes in K2 values and values of
      corneal thickness postoperatively.Key words: keratoconus, ectasia, accelerated
      corneal cross-linking.

PMID- 29589461
TI  - [Pars Plicata Vitrectomy in Premature Newborns for Retinal Detachment as a Result
      of Retinopathy of Prematurity, our Results].
AB  - INTRODUCTION: The aim of this work is to evaluate our own results of surgical
      treatment of retinal detachment in immature newborns. Retinopathy of prematurity
      (ROP) is one of the most complicated ocular disorders, both in terms of diagnosis
      and therapy. It is a potentially blinding illness that arises from the incomplete
      development of the bloodstream of the neuroretina of preterm infants. Currently,
      the most effective therapy is ablation of the avascular retina by laser
      photocoagulation or cryocoagulation. Despite this treatment, the immature retina
      may develop it's detachment. METHODOLOGY: We report 2 case-reports, retrospective
      results of 4-eyes in 2 patients with severe ocular and overall complications of
      prematurity. The ocular background of preterm babies was investigated in
      arteficial mydriasis by an indirect ophthalmoscope, and later with the RetCam
      photographic device. The ROP stages were evaluated according to the ICROP
      classification. All eyes were treated with cryo-retinopexy at the threshold stage
      of ROP, followed by intraocular surgery for progression of traction retinal
      detachment. The surgical technique was a 3-port 25-G PPV (pars-plicata
      vitrectomy) with insertion of ports 1.5 mm from limbus. The PPV was performed
      using the Constellation (ALCON) operating unit, controlling the intraocular
      pressure for 15 torr. The assessment of visual acuity was performed according to
      the scale: no light perception (no response of the child to light), light
      sensitivity (positive or negative reaction to illumination), fixation of light.
      RESULTS: The retina stayed attached in all operated eyes, more in each case
      report. CONCLUSION: Contemporary vitreoretinal surgery allows for the anatomical
      success of traction retinal detachment surgery during ROP already in neonatal
      age.Key words: retinal detachment, retinopathy of prematurity, PPV, surgery.

PMID- 29589462
TI  - [Brown's Syndrome: the Various forms and Their Treatment (Including an Expander
      own Design)].
AB  - AIM: Familiar with the treatment of various forms of Browns syndrome and its
      success. To document preparation of the expander own design. MATERIAL AND
      METHODS: In the years 1996-2016 was operated 33 pacients with congenital Browns
      syndrome by using an extension of its tendon expander at the Eye Clinic of the
      University Hospital Vinohrady in Prague. Author proves photographs preparing
      expander own design and modified surgical technique. It was also operated on 10
      patients for accompanying Y-exotropia. Eleven patients with acute form of Brown's
      syndrome in the pulley of upper oblique muscle applied Betamethasoni. RESULTS:
      The using expander own design - non-resorbable Ethibond 5-0 cauted silicone
      cannula - held at congenital form of Browns syndrome, without a weighty
      complication or its exclusion in the period. The result of the performance was
      determined age of patients at the time of implantation of the expander.
      Preschoolers postoperative condition was fully compliant, this expander
      standardized vertical mobility. The vertical alignment motility is reduced with
      advancing age, especially in adulthood. Optimal surgical procedures at Y
      exotropia were antepozice with recession of the inferior oblique muscle possibly
      supplemented by retroposition ipsilateral external rectus. The application
      efficiency of Betamethasoni for acute form of Brown's syndrome in the pulley of
      upper oblique muscle was successful in only two weeks after the initial symptoms
      vertical diplopia. CONCLUSION: Expander own design which represented non
      resorbable Ethibond cauted silicone cannula was very effective in dealing with
      congenital form of Browns syndrome. The application of glucocorticoids in the
      pulley of upper oblique muscle should always be a quantity result.Key words:
      Browns syndrome, Betamethasoni, expander, Ethibond, silicone cannula, Y -
      exotropia.

PMID- 29589463
TI  - [IN VIVO CORNEAL CONFOCAL MICROSCOPY: BASIC PRINCIPLES AND APPLICATIONS Corneal
      confocal microscopy is a new, non-invasive imaging].
AB  - Corneal confocal microscopy is a new, non-invasive imaging method. It provides
      serial images of a face optical sections through the full-thickness of the living
      cornea, avoiding artefacts associated with ex vivo study. It provides qualitative
      as well as quantitative analysis of the corneal layers, nerves, and cells. It
      also allows longitudinal examination of the corneal structure changes over time.
      The purpose of this article is to describe the principles and capabilities of the
      currently available corneal confocal microscopes, and possible applications of
      this tool.Key words: confocal microscopy, cornea.

PMID- 29589464
TI  - [POSSIBILITIES OF IN VIVO CORNEAL CONFOCAL MICROSCOPY OF CORNEAL NERVES IN
      DIABETES].
AB  - In vivo corneal confocal microscopy (CCM) represents a new, non-invasive, rapidly
      developing corneal examination technique that enables individual layers of the
      cornea to be displayed at the cellular level. The cornea is the translucent and
      at the same time the most innervated tissue of the human body. Diabetic
      neuropathy (DN) is a serious complication of diabetes mellitus (DM). A close
      correlation has been demonstrated between the development of diabetic neuropathy
      and the pathological changes of the corneal subbasal plexus. Currently, great
      attention is directed towards the possibility of using CCM to determine early DN.
      Interestingly, changes in nerve plexus in the cornea precede the clinical
      manifestations of DN. Our work aims to give a comprehensive overview of the
      current possibilities and trends in use of in vivo CCM in connection with DN
      evaluation. In vivo CCM becomes important in the search for patients at risk of
      developing DN, in early diagnosis of DN in pre-symptomatology, in quantifying
      severe DN, in monitoring and evaluating the therapeutic response to DM treatment.
      In addition to its diagnostic and preventive significance, it is a research tool
      important for understanding the pathophysiology of DM changes.Key words: confocal
      microscopy, cornea, small fibre neuropathy, diabetes mellitus, diabetic
      neuropathy.

PMID- 29589465
TI  - Genotypic Characterization of Human Immunodeficiency Virus Type 1 Prevalent in
      Kepulauan Riau, Indonesia.
AB  - Kepulauan Riau is a famous tourist destination in Indonesia. The epidemic of
      human immunodeficiency virus type 1 (HIV-1) infection is gradually increasing in
      this region. We collected peripheral blood samples from 62 antiretroviral therapy
      experienced individuals. The amplification of viral genomic fragments, HIV-1
      subtyping, and the detection of HIV drug resistance (HIVDR) were performed. Viral
      subtyping revealed that the most prevalent HIV-1 subtype/circulating recombinant
      form (CRF) was CRF01_AE (55.6%), followed by recombinants between CRF01_AE and
      subtype B (17.8%) and then subtype B (15.6%). Recombinants containing CRF02_AG
      gene fragments were also detected (11.1%). Regarding HIVDR, no drug resistance
      associated major mutations were found in pol genes encoding protease, although
      minor mutations were frequently detected. Furthermore, major mutations, including
      M184V (2.2%) and Y188L (2.2%), were identified in the viral pol gene encoding
      reverse transcriptase derived from a study participant, suggesting that the
      prevalence of HIVDR is low in the region.

PMID- 29589466
TI  - A systematic review of epidemiologic studies of styrene and cancer.
AB  - Previous epidemiology reviews of exposure to styrene and the risk of cancer
      considered studies published through 13 November 2013. Since then, additional
      relevant research has been published. No review has included meta-analyses. The
      current systematic review considered research published through June 2017;
      included meta-analyses of the relationship between any exposure to styrene and
      cancers identified as being of concern, including non-Hodgkin lymphoma (NHL),
      leukemia and cancers of the esophagus, pancreas, lung and kidney; and evaluated
      several other forms of cancer. Meta-relative risks for all studies were 1.14 (95%
      confidence interval (CI), 0.91-1.43) for NHL, 1.00 (95% CI, 0.80-1.26) for
      multiple myeloma, 0.98 (95% CI, 0.87-1.09) for all leukemia, 1.03 (95% CI, 0.92
      1.15) for esophageal cancer, 1.02 (95% CI, 0.93-1.12) for pancreatic cancer, 1.09
      (95% CI, 0.95-1.24) for lung cancer and 1.10 (95% CI, 0.99-1.22) for kidney
      cancer. Individual studies provided little evidence of exposure-response or
      induction time trends. Limitations of the available research and of the meta
      analyses included reliance in most studies on mortality data rather than on
      incidence data, lack of quantitative estimates of styrene exposure for individual
      subjects and lack of information on lifestyle factors. Consideration of all
      pertinent data, including substantial recent research, indicates that the
      epidemiologic evidence on the potential carcinogenicity of styrene is
      inconclusive and does not establish that styrene causes any form of cancer in
      humans.

PMID- 29589467
TI  - Meta-analysis of individual registry results enhances international registry
      collaboration.
AB  - Background and purpose - Although common in medical research, meta-analysis has
      not been widely adopted in registry collaborations. A meta-analytic approach in
      which each registry conducts a standardized analysis on its own data followed by
      a meta-analysis to calculate a weighted average of the estimates allows
      collaboration without sharing patient-level data. The value of meta-analysis as
      an alternative to individual patient data analysis is illustrated in this study
      by comparing the risk of revision of porous tantalum cups versus other uncemented
      cups in primary total hip arthroplasties from Sweden, Australia, and a US
      registry (2003-2015). Patients and methods - For both individual patient data
      analysis and meta-analysis approaches a Cox proportional hazard model was fit for
      time to revision, comparing porous tantalum (n = 23,201) with other uncemented
      cups (n = 128,321). Covariates included age, sex, diagnosis, head size, and stem
      fixation. In the meta-analysis approach, treatment effect size (i.e., Cox model
      hazard ratio) was calculated within each registry and a weighted average for the
      individual registries' estimates was calculated. Results - Patient-level data
      analysis and meta-analytic approaches yielded the same results with the porous
      tantalum cups having a higher risk of revision than other uncemented cups (HR
      (95% CI) 1.6 (1.4-1.7) and HR (95% CI) 1.5 (1.4-1.7), respectively). Adding the
      US cohort to the meta-analysis led to greater generalizability, increased
      precision of the treatment effect, and similar findings (HR (95% CI) 1.6 (1.4
      1.7)) with increased risk of porous tantalum cups. Interpretation - The meta
      analytic technique is a viable option to address privacy, security, and data
      ownership concerns allowing more expansive registry collaboration, greater
      generalizability, and increased precision of treatment effects.

PMID- 29589468
TI  - Response to 'Pitfalls of big data'.

PMID- 29589469
TI  - Assessing speech, language and communication difficulties in children referred
      for ADHD: A qualitative evaluation of a UK child and adolescent mental health
      service.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most
      common childhood neuropsychiatric disorders and is highly comorbid with speech,
      language and communication difficulties (SLCDs). However, it is unclear how often
      SLCDs are identified in ADHD referrals in routine practice and whether there are
      unidentified SLCDs within this population. METHOD: A thematic analysis was
      conducted on a random sample of case notes from 18 referrals for ADHD made to a
      child and adolescent mental health service (CAMHS) in London, United Kingdom.
      Analyses aimed to identify (a) the types of SLCDs detected during assessment, (b)
      at which point of the episode of care these SLCDs were suspected and (c) whether
      a referral or consultation was made to a speech and language therapist (SLT) for
      further evaluation. RESULTS: Out of 18 cases investigated, 15 were found to have
      possible SLCDs based on case notes and reports provided by external agencies.
      However, only four were referred by CAMHS for further assessment. It is unclear
      what, if any, steps other external agencies took. Themes describing types of
      SLCDs, comorbidities and the process of identification are discussed. CONCLUSION:
      The analysis of this service's case notes revealed a range of different routes to
      the identification of SLCDs, and it was unclear what steps were taken as a result
      of assessment. A limitation is that this is just one service and the results may
      not generalise. However, given the similarity in practitioner training received
      across the country and that practitioners move from service to service, there are
      grounds for repeating the study in other services. We recommend a more structured
      approach to identifying SLCDs and recording assessment and treatment decisions
      made.

PMID- 29589470
TI  - The merit of tyrosine kinase inhibitors in the adjuvant setting of high-risk
      renal cell carcinoma: a meta-analysis.
AB  - AIM: As no meta-analyses have evaluated tyrosine kinase inhibitors in the
      adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate
      the benefit of sunitinib and pazopanib in the adjuvant setting. METHODS: This
      meta-analysis included all Phase III randomized controlled trials evaluating
      adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the
      comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and
      placebo. RESULTS: There was a tendency for significant overall effect of both
      sunitinib and pazopanib on DFS (hazard ratio: 0.85; 95% confidence interval: 0.72
      1.01; p = 0.06). There was no significant difference between the effect of
      sunitinib and pazopanib on DFS (p = 0.51;  I2 = 0%). CONCLUSION: Pazopanib and
      sunitinib could prolong DFS in the adjuvant treatment of high-risk RCC and seem
      equally effective in this setting.

PMID- 29589471
TI  - De-escalating treatment in the adjuvant setting in HER2-positive breast cancer.
AB  - The decision to offer adjuvant therapy to patients with early-stage cancer relies
      on factors related to the risk of disease recurrence, degree of benefit with the
      proposed therapy and the associated risk of toxicities. For patients with stages
      II and III HER2-positive breast cancer, administering 1 year of trastuzumab plus
      comprehensive chemotherapy is the standard of care. However, the pivotal adjuvant
      trials had very few older patients and patients with small HER2-positive tumors.
      In this review, we will discuss the clinical data regarding strategies to de
      escalate adjuvant systemic therapy in patients with early stage HER2-positive
      disease.

PMID- 29589472
TI  - Anti-inflammatory and antiproliferative prenylated chalcones from Hedysarum
      gmelinii.
AB  - Five new prenylated chalcones hedysarumines C-G (1-5), along with eight known
      chalcones (6-13) all of which were isolated from the genus Hedysarum for the
      first time, were isolated from the roots of Hedysarum gmelinii by chromatographic
      methods. Their structures were determined by extensive spectroscopic techniques.
      The isolated chalcones (2-13) and previously isolated prenylated chalcones (14
      16) were evaluated for antiproliferative activity against five human cancer cell
      lines (HepG2, A549, Du145, BGC823, and HCT116) and in vitro anti-inflammatory
      activity. Compounds 5, 10, and 15 inhibited NO production induced by
      lipopolysaccharide in BV-2 cells, with IC50 values ranging from 3.25 to 8.48 MUM.
      Compounds 4 and 11 showed moderate antiproliferative activity to selective human
      cancer cell lines, with the IC50 values of 4 and 11 against A549 cell line being
      7.79 and 9.67 MUM, respectively, and the IC50 value of 11 against HCT116 cell
      line being 8.85 MUM.

PMID- 29589473
TI  - Evaluation of Point-of-Care Resources for Dietary Supplement Information.
AB  - OBJECTIVE: To evaluate 6 tertiary, point-of-care drug information resources'
      dietary supplement content. METHODS: This was a cross-sectional evaluation of
      Lexicomp Natural Products Database, Micromedex Alternative Medicine, Clinical
      Pharmacology, Natural Medicines, The Review of Natural Products, and Handbook of
      Nonprescription Drugs. Each resource was evaluated for scope, completeness,
      consistency, and ease of use. RESULTS: For a sample of 66 supplements, scope
      scores ranged from 69.7% (Micromedex) to 100% (Natural Medicines). Completeness
      scores were high considering uses, dose, adverse effects, and mechanism (85.7% to
      100%). Overall completeness scores ranged from 82.5% ( Handbook of
      Nonprescription Drugs) to 100% (Clinical Pharmacology, Natural Medicines, The
      Review of Natural Products). Consistency scores ranged from 0% ( Handbook of
      Nonprescription Drugs) to 100% (Natural Medicines, The Review of Natural
      Products). Mean time to locate and gather information was similar among groups.
      CONCLUSIONS: Resources were similar for completeness and ease of use. Scope and
      consistency varied depending on the resource.

PMID- 29589474
TI  - What influences decisions about ongoing stroke rehabilitation for patients with
      pre-existing dementia or cognitive impairment: a qualitative study?
AB  - OBJECTIVE: To identify factors influencing clinicians decision-making about
      ongoing stroke rehabilitation for people with pre-existing dementia/cognitive
      impairment and the impact on clinical practice. DESIGN: Qualitative semi
      structured interviews with stroke specialist healthcare professionals analysed
      using thematic analysis. SETTING: Acute stroke unit, inpatient stroke
      rehabilitation units, and community stroke services. PARTICIPANTS: Twenty three
      professionals from six multidisciplinary stroke teams involved in decision-making
      about stroke patients' rehabilitation potential and clinical pathways. RESULTS:
      Factors influencing decision-making about ongoing rehabilitation were (1) gaining
      understanding of the individual patient, (2) clinician's knowledge of
      dementia/cognitive impairment, (3) predicting rehabilitation potential, (4)
      organizational constraints, and (5) clinician's perceptions of their role within
      the team. Decision-making led to two outcomes, either accommodating the pre
      existing dementia/cognitive impairment within delivery of rehabilitation or
      ending rehabilitation for that patient to allocate limited resources where they
      were perceived more likely to be effective. Participants felt that patients with
      pre-existing dementia/cognitive impairment had difficulty demonstrating the
      required rehabilitation potential within the short timescales available in the
      current model of service delivery. Participants identified a need for training to
      improve their knowledge and confidence for decision-making and delivery of
      rehabilitation for this growing population. CONCLUSION: Clinicians' decision
      making about ongoing rehabilitation for patients with prestroke
      dementia/cognitive impairments is influenced by gaps in their knowledge and by
      service constraints. Increased training and more flexible, patient-centred
      services would enable clinicians to better accommodate these patients in
      rehabilitation.

PMID- 29589475
TI  - Analysis of indirect treatment comparisons in national health technology
      assessment assessments and requirements for industry submissions.
AB  - AIM: To determine the preferred methodologies of health technology assessment
      (HTA) agencies across Europe, Canada and Australia to ascertain acceptance of
      indirect treatment comparisons (ITC) as a source of comparative evidence. METHOD:
      A review of official submission guidelines and analysis of comments in HTA
      submissions that have used different ITC methodologies. CONCLUSION: ITC is
      generally accepted as a technique that allows demonstration of noninferiority to
      a comparator provided the chosen methodology and underlying assumptions are clear
      and justified. However, HTA agencies are more likely to closely scrutinize
      submitted data and evaluate statistical significance of results when superiority
      is claimed. In addition, the HTA agencies in scope tended to be cautious and only
      accept ITC data as support for similarity of treatments.

PMID- 29589476
TI  - Antibacterial activities of a series of novel 5-O-(4', 6'-O-dimodified)
      mycaminose 14-membered ketolides.
AB  - A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were
      assessed for their in vitro antibacterial activities against a panel of sensitive
      and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the
      best antibacterial activities against several macrolide-sensitive and macrolide
      resistant strains. These results indicated that introducing ester to 6-OH and a
      small volume ether substituent to the 4-OH of mycaminose could improve the
      antibacterial activities of ketolides.

PMID- 29589477
TI  - Drug repositioning for novel antitrichomonas from known antiprotozoan drugs using
      hierarchical screening.
AB  - AIM: Metronidazole is the most widely used drug in trichomoniasis therapy.
      However, the emergence of metronidazole-resistant Trichomonas vaginalis isolates
      calls for the search for new drugs to counter the pathogenicity of these
      parasites. RESULTS: Classification models for predicting the antitrichomonas
      activity of molecules were built. These models were employed to screen
      antiprotozoal drugs, from which 20 were classified as active. The in vitro
      experiments showed moderate to high activity for 19 of the molecules at 10
      MUg/ml, while 3 compounds yielded higher activity than the reference at 1 MUg/ml.
      The 11 most active chemicals were evaluated in vivo using Naval Medical Research
      Institute (NMRI) mice. CONCLUSION: Benznidazole showed similar results as
      metronidazole, and can thus be considered as a potential candidate in
      antitrichomonas therapy.

PMID- 29589478
TI  - Advantages and disadvantages of interdisciplinary consultation in the
      prescription of assistive technologies for mobility limitations.
AB  - PURPOSE: To explore the advantages and disadvantages experienced by professionals
      in interdisciplinary consultation involving the user, prescriber and technician
      in the prescription of assistive technologies for mobility limitations. METHOD:
      Cross-sectional study. Prescribers (N = 39) and orthopaedic technicians (N = 50),
      who were regularly involved in an interdisciplinary consultation completed a
      questionnaire about advantages and disadvantages of the interdisciplinary
      consultation. RESULTS: Advantages of the interdisciplinary consultation were
      mentioned within all CanMEDS areas of medical practice, including better and
      quicker prescription of the assistive technology, shared knowledge of medical
      diagnosis and device possibilities, shared decision making of the device
      prescription and clear communication rules. Disadvantages were mentioned in the
      CanMEDS areas management and collaboration, including planning problems
      (financial) reimbursement of this type of consultation, and time efficiency. On a
      10-point scale, mean (standard deviation) rates of interdisciplinary
      consultations were 7.9 (0.6) according to prescribers, and 7.8 (0.9) by
      technicians. All participants wanted to continue the interdisciplinary
      consultation. CONCLUSIONS: Prescribers and technicians in the field of assistive
      technologies for walking mobility limitations appreciate an interdisciplinary
      consultation. Advantages are found in all CanMEDS areas, whereas disadvantages
      only concern coordination. It should be encouraged to realize this kind of
      consultation in all situations where such technologies are prescribed.
      Implications for rehabilitation Interdisciplinary consultation involving the
      user, prescriber and technician to prescribe assistive technologies for mobility
      limitations has many advantages in all CanMEDS areas of medical practice, and few
      disadvantages, related to management and collaboration only. The disadvantages of
      interdisciplinary consultation, such as (financial) reimbursement by health
      insurance companies, have to be taken into account. Professionals in the field of
      ankle-foot-orthoses and orthopaedic shoes (medical specialist as prescriber and
      orthopaedic technician) who are involved in interdisciplinary consultation
      appreciate it and want to continue.

PMID- 29589479
TI  - Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.
AB  - Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for
      the management of peritoneal disseminations of digestive and gynecological
      cancers. Nevertheless, a poor drug penetration is one key drawback of IP
      chemotherapy since peritoneal neoplasms are notoriously resistant to drug
      penetration. Recent preclinical studies have focused on targeting the aberrant
      tumor microenvironment to improve intratumoral drug transport. However, tumor
      stroma targeting therapies have limited therapeutic windows and show variable
      outcomes across different cohort of patients. Therefore, the development of new
      strategies for improving the efficacy of IP chemotherapy is a certain need. In
      this work, we propose a new magnetically assisted strategy to elevate drug
      penetration into peritoneal tumor nodules and improve IP chemotherapy. A
      computational model was developed to assess the feasibility and predictability of
      the proposed active drug delivery method. The key tumor pathophysiology,
      including a spatially heterogeneous construct of leaky vasculature, nonfunctional
      lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico.
      The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside
      tumors was simulated and compared with the transport of free cytotoxic agents.
      Our results on magnetically assisted delivery showed an order of magnitude
      increase in the final intratumoral concentration of drug-coated MNPs with respect
      to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300
      nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors
      while the MDT performance remains essentially the same over a large particle
      radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in
      larger tumors (5-10 mm in radius) was found to be markedly dependent on the
      choice of magnet strength and tumor-magnet distance while these two parameters
      were less of a concern in small tumors. We also validated in silico results
      against experimental results related to tumor interstitial hypertension,
      conventional IP chemoperfusion, and magnetically actuated movement of MNPs in
      excised tissue.

PMID- 29589480
TI  - Threshold values of ankle dorsiflexion and gross motor function in 60 children
      with cerebral palsy.
AB  - Background and purpose - Threshold values defining 3 categories of passive range
      of motion are used in the Cerebral Palsy follow-Up Program to guide clinical
      decisions. The aim of this study was to investigate the threshold values by
      testing the hypothesis that passive range of motion in ankle dorsiflexion is
      associated with gross motor function and that function differs between the groups
      of participants in each category. Patients and methods - We analyzed data from 60
      ambulatory children (aged 5-9 years) with spastic cerebral palsy. Outcomes were
      passive range of motion in ankle dorsiflexion with flexed and extended knee and
      gross motor function (Gait Deviation Index, Gait Variable Score of the ankle,
      peak dorsiflexion during gait, 1-minute walk, Gross Motor Function Measure, the
      Pediatric Quality of Life Inventory Cerebral Palsy Module, and Pediatric Outcomes
      Data Collection Instrument). Results - Significant (p < 0.05) and moderate
      correlations were documented for range of motion versus Gait Variable Score of
      the ankle (r = -0.37 and r = -0.37) and range of motion versus peak dorsiflexion
      (r = 0.49 and r = 0.55). Differences between the groups formed by the categories
      were shown for Gait Variable Score of the ankle and peak dorsiflexion (p < 0.05).
      No other significant correlations or differences between the categories were
      observed. Interpretation - The results suggest that threshold values for ankle
      dorsiflexion used in the Cerebral Palsy follow-Up Program are of limited clinical
      value in assessing overall gross motor function, but may be used to identify
      deviations in ankle-specific gait function.

PMID- 29589481
TI  - Exploring the Potential of Participatory Theatre to Reduce Stigma and Promote
      Health Equity for Lesbian, Gay, Bisexual, and Transgender (LGBT) People in
      Swaziland and Lesotho.
AB  - Stigma and discrimination affecting lesbian, gay, bisexual, and transgender
      (LGBT) people compromise health and human rights and exacerbate the HIV epidemic.
      Scant research has explored effective LGBT stigma reduction strategies in low-
      and middle-income countries. We developed and pilot-tested a participatory
      theatre intervention (PTI) to reduce LGBT stigma in Swaziland and Lesotho,
      countries with the world's highest HIV prevalence. We collected preliminary data
      from in-depth interviews with LGBT people in Lesotho and Swaziland to enhance
      understanding of LGBT stigma. Local LGBT and theatre groups worked with these
      data to create a 2-hour PTI composed of three skits on LGBT stigma in health
      care, family, and community settings in Swaziland (Manzini) and Lesotho (Maseru,
      Mapoteng). Participants ( n = 106; nursing students, health care providers,
      educators, community members) completed 12 focus groups following the PTI. We
      conducted thematic analysis to understand reactions to the PTI. Focus groups
      revealed the PTI increased understanding of LGBT persons and issues, increased
      empathy, and fostered self-reflection of personal biases. Increased understanding
      included enhanced awareness of the negative impacts of LGBT stigma, and of LGBT
      people's lived experiences and issues. Participants discussed changes in attitude
      and perspective through self-reflection and learning. The format of the theatre
      performance was described as conducive to learning and preferred over more
      conventional educational methods. Findings indicate changed attitudes and
      awareness toward LGBT persons and issues following a PTI in Swaziland and
      Lesotho. Stigma reduction interventions may help mitigate barriers to HIV
      prevention, treatment, and care in these settings with a high burden of HIV.

PMID- 29589482
TI  - Psychosocial Determinants of Food Acquisition and Preparation in Low-Income,
      Urban African American Households.
AB  - BACKGROUND: Psychosocial factors are important determinants of health behaviors
      and diet-related outcomes, yet relatively little work has explored their relation
      to food-purchasing and preparation behaviors in low-income populations. AIM: To
      evaluate the psychosocial factors associated with food-related behaviors.
      METHODS: Cross-sectional data collected from 465 low-income African American
      adult caregivers in the baseline evaluation of the B'more Healthy Communities for
      Kids obesity prevention trial. Questionnaires were used to assess household
      sociodemographic characteristics, food sources frequently used, and food
      preparation and food acquisition behaviors. Multiple linear regression models
      explored the associations between caregiver psychosocial variables and food
      related behaviors, controlling for caregivers' age, sex, household income,
      household size, and food assistance participation. RESULTS: Caregivers purchased
      prepared food at carry-outs on average 3.8 times (standard deviation [ SD] = 4.6)
      within 30 days. Less healthy foods were acquired 2 times more frequently than
      healthier foods ( p < .001). Higher food-related behavioral intention and self
      efficacy scores were positively associated with healthier food acquisition (beta
      = 0.7; 95% confidence interval [CI] [0.09, 1.4]; beta = 0.04; 95% CI [0.02,
      0.06]) and negatively associated with frequency of purchasing at prepared food
      sources (beta = -0.4; 95% CI [-0.6, -0.2]; beta = -0.5; 95% CI [-0.7, -0.3]),
      respectively. Higher nutrition knowledge was associated with lower frequency of
      purchasing food at prepared food venues (beta = -0.7; 95% CI: [-1.2, -0.2]).
      DISCUSSION: Our findings indicate a positive association between psychosocial
      determinants and healthier food acquisition and food preparation behaviors.
      CONCLUSION: Interventions that affect psychosocial factors (i.e., food-related
      behavioral intentions and self-efficacy) may have the potential to increase
      healthier food preparation and food-purchasing practices among low-income African
      American families.

PMID- 29589483
TI  - Discovery, gene modification, and optimization of fermentation of an enduracidin
      producing strain.
AB  - Enduracidin significantly inhibits Gram-positive bacteria and had been widely
      used in many fields. However, as the poor technology for production of
      enduracidin and its scarcity, identification of novel strategies for production
      of enduracidin is important. Our group developed two methods to improve the yield
      of the production of enduracidin. The yield of enduracidin was increased by three
      to fivefold. The highest yields of enduracidin A and enduracidin B achieved were
      63.7 and 82.13 mg/ml. Thus, our results might provide a new reference method for
      the industrial production of enduracidin.

PMID- 29589484
TI  - New secoiridoids from the fruits of Ligustrum lucidum.
AB  - Three new secoiridoids, nuezhenelenoliciside (1), isojaslanceoside B (2), 6'-O
      trans-cinnamoyl-secologanoside (3), were isolated from the dried fruits of
      Ligustrum lucidum. Their structures were elucidated by comprehensive
      spectroscopic analysis. Among them, 1 featured a rare rearrangement product of
      secoiridoid, which underwent the cleavage of chemical bond between C-1 and O-2,
      and the reformation of a new iridoid ring between C-8 and O-2. In addition, all
      compounds were tested for their osteogenic activity on pre-osteoblastic MC3T3-E1
      cells. As a result, 1 and 3 exhibited potent effects on promoting cell
      proliferation of pre-osteoblast cells.

PMID- 29589485
TI  - Characterization of a New HIV-1 CRF01_AE/CRF07_BC Recombinant Virus Form Among
      Men Who Have Sex with Men in Beijing, China.
AB  - Recent studies have revealed that three major viral strains (CRF07_BC, CRF01_AE,
      and subtype B) have been cocirculating among men who have sex with men in
      Beijing. Cocirculation of multiple subtypes in the same population contributes
      significantly to the emergence of recombinant viruses. This study reports a near
      full-length genome of a novel, second-generation HIV-1 recombinant (BJ2015EU16)
      between CRF07_BC and CRF01_AE. The analysis of BJ2015EU16 shows that the genome
      comprises three interlaced segments, including two CRF07_BC and one CRF01_AE
      segments, with CRF07_BC as the backbone. There were two recombinant breakpoints
      in the vpu and env genes of BJ2015EU16. This is different from a previously
      identified CRF01_AE/07_BC recombinant strain from Beijing. The new emergence of
      the unique recombinant form increases the complexity of the HIV epidemic in the
      Beijing homosexual group, and the ongoing generation of recombinant viruses may
      provide an important basis for future analysis of the recombination mechanism of
      HIV-1.

PMID- 29589486
TI  - Advances in chemical pharmacotherapy for the treatment of pediatric immune
      thrombocytopenia.
AB  - INTRODUCTION: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder of
      heterogeneous pathophysiological mechanisms. Treatment endpoints include
      elevation of platelets and reduction of bleeding risk, elevation of quality of
      life, reduction of concomitant therapies and prevention from bleeding. Persistent
      and chronic ITP is more common in adults but occurs in children. Standard
      therapies include corticosteroids and immunoglobulins, both associated with side
      effects. There are new treatments, such as thrombopoietin-receptor agonists and
      promising investigational drugs. Areas covered: Experience from the management of
      adults is valuable for children with persistent and chronic symptomatic ITP. In
      this review first- and second-line therapies, but also investigational drugs for
      children with ITP are discussed. Expert opinion: Although time-consuming and
      based on experience, children with no or mild bleeding can be safely managed with
      a watch and wait strategy. Chronic symptomatic immune thrombocytopenia is an area
      of second-line treatments based on a highly individualized approach. Furthermore,
      there are investigational drugs, which may also be of benefit for children with
      chronic symptomatic ITP.

PMID- 29589487
TI  - Search of vasopressin analogs with antiproliferative activity on small-cell lung
      cancer: drug design based on two different approaches.
AB  - AIM: Development of compounds with therapeutic application requires the
      interaction of different disciplines. Several tumors express vasopressin (AVP;
      arginine vasopressin) receptors with contrasting effects depending on receptor
      subtype. Desmopressin (dDAVP) is an AVP-selective analog with antiproliferative
      properties. In this work, an evolutionary approach and a rational strategy were
      applied in order to design novel AVP analogs. RESULTS: We designed two novel
      analogs; dDInotocin (dDINT, insect analog), and [V4Q5]dDAVP, and demonstrated the
      importance of the dDAVP conformational loop for its antiproliferative activity.
      [V4Q5] dDAVP showed major cytostatic effect on lung cancer cells than dDAVP and
      its cytostatic effect was abolished by V2R blockade. CONCLUSION: Combination of
      these strategies could provide the basis for future studies for the development
      of improved compounds with potential therapeutic applications.

PMID- 29589488
TI  - Associations between gene polymorphisms and treatment outcomes of methotrexate in
      patients with juvenile idiopathic arthritis.
AB  - AIM: Performance of a meta-analysis with respect to the genetic predictors of
      methotrexate (MTX) treatment outcomes, efficacy and toxicity, in patients with
      juvenile idiopathic arthritis (JIA). METHODS: Databases of OVID MEDLINE and OVID
      EMBASE were searched to collect the studies addressing correlations between gene
      polymorphisms and efficacy and/or toxicity in MTX-treated JIA patients. Pooled
      odds ratios (ORs) with 95% CIs were estimated in allelic, recessive and/or
      dominant models. RESULTS: With regards to efficacy, the C677T (rs1801133)
      polymorphism in MTHFR was associated with nonresponse to MTX treatment in a
      recessive model (OR: 0.40; 95% CI: 0.19-0.84). For associations with toxicity,
      the MTHFR C677T (rs1801133) polymorphism was associated with presenting overall
      adverse events in an allelic model (OR: 1.54; 95% CI: 1.07-2.22) and a dominant
      model (OR: 1.70; 95% CI: 1.08-2.68). CONCLUSION: C677T (rs1801133) polymorphism
      in MTHFR predicts nonresponse and/or adverse effects of MTX treatment in JIA
      patients.

PMID- 29589489
TI  - Infographic: Triclosan-coated sutures and surgical site infections after hip and
      knee arthroplasty.

PMID- 29589491
TI  - Risk factors for progression of articular cartilage damage after anatomical
      anterior cruciate ligament reconstruction.
AB  - Aims: To investigate the risk factors for progression of articular cartilage
      damage after anatomical anterior cruciate ligament (ACL) reconstruction. Patients
      and Methods: A total of 174 patients who underwent second-look arthroscopic
      evaluation after anatomical ACL reconstruction were enrolled in this study. The
      graded condition of the articular cartilage at the time of ACL reconstruction was
      compared with that at second-look arthroscopy. Age, gender, body mass index
      (BMI), ACL reconstruction technique, meniscal conditions, and other variables
      were assessed by regression analysis as risk factors for progression of damage to
      the articular cartilage. Results: In the medial compartment, multivariable
      logistic regression analysis indicated that partial medial meniscectomy (odds
      ratio (OR) 6.82, 95% confidence interval (CI) 2.11 to 22.04, p = 0.001), pivot
      shift test grade at the final follow-up (OR 3.53, CI 1.39 to 8.96, p = 0.008),
      BMI (OR 1.15, CI 1.03 to 1.28, p = 0.015) and medial meniscal repair (OR 3.19, CI
      1.24 to 8.21, p = 0.016) were significant risk factors for progression of
      cartilage damage. In the lateral compartment, partial lateral meniscectomy (OR
      10.94, CI 4.14 to 28.92, p < 0.001) and side-to-side differences in anterior knee
      laxity at follow-up (OR 0.63, p = 0.001) were significant risk factors.
      Conclusion: Partial meniscectomy was found to be strongly associated with the
      progression of articular cartilage damage despite r anatomical ACL
      reconstruction. Cite this article: Bone Joint J 2018;100-B:285-93.

PMID- 29589492
TI  - Predictors of compartment syndrome of the foot after fracture of the calcaneus.
AB  - Aims: Identifying predictors of compartment syndrome in the foot after a fracture
      of the calcaneus may lead to earlier diagnosis and treatment. The aim of our
      study was to identify any such predictors. Patients and Methods: We
      retrospectively reviewed 303 patients (313 fractures) with a fracture of the
      calcaneus who presented to us between October 2008 and September 2016. The
      presence of compartment syndrome and potential predictors were identified by
      reviewing their medical records. Potential predictors included age, gender,
      concomitant foot injury, mechanism of injury, fracture classification, time from
      injury to admission, underlying illness, use of anticoagulant/antiplatelet
      agents, smoking status and occupation. Associations with predictors were analyzed
      using logistic regression analysis. Results: Of the 313 fractures of the
      calcaneus, 12 (3.8%) developed a compartment syndrome. A Sanders type IV fracture
      was the only strongly associated factor (odds ratio 21.67, p = 0.007). Other
      variables did not reach statistical significance. Conclusion: A Sanders type IV
      fracture is the best predictor of compartment syndrome after a fracture of the
      calcaneus. Cite this article: Bone Joint J 2018;100-B:303-8.

PMID- 29589493
TI  - Lateral condylar fractures of the humerus in children.
AB  - Aims: Displaced fractures of the lateral condyle of the humerus are frequently
      managed surgically with the aim of avoiding nonunion, malunion, disturbances of
      growth and later arthritis. The ideal method of fixation is however not known,
      and treatment varies between surgeons and hospitals. The aim of this study was to
      compare the outcome of two well-established forms of surgical treatment,
      Kirschner wire (K-wire) and screw fixation. Patients and Methods: A retrospective
      cohort study of children who underwent surgical treatment for a fracture of the
      lateral condyle of the humerus between January 2005 and December 2014 at two
      centres was undertaken. Pre, intraoperative and postoperative characteristics
      were evaluated. A total of 336 children were included in the study. Their mean
      age at the time of injury was 5.8 years (0 to 15) with a male:female patient
      ratio of 3:2. A total of 243 (72%) had a Milch II fracture and the fracture was
      displaced by > 2 mm in 228 (68%). In all, 235 patients underwent K-wire fixation
      and 101 had screw fixation. Results: There was a higher rate of nonunion with K
      wire fixation (p = 0.02). There was no difference in Baumann's angle, carrying
      angle or the rate of major complications between the two groups. No benefit was
      obtained by immobilizing the elbow for more than four weeks in either group. No
      short-term complications were seen when fixation crossed the lateral ossific
      nucleus. Conclusion: Fixation of lateral condylar humeral fractures in children
      using either K-wires or screws gives satisfactory results. Proponents of both
      techniques may find justification of their methods in our data, but prospective,
      randomized trials with long-term follow-up are required to confirm the findings,
      which suggest a higher rate of nonunion with K-wire fixation. Cite this article:
      Bone Joint J 2018;100-B:387-95.

PMID- 29589494
TI  - Intercalary reconstruction of femur after tumour resection: is a vascularized
      fibular autograft plus allograft a long-lasting solution?
AB  - Aims: After intercalary resection of a bone tumour from the femur, reconstruction
      with a vascularized fibular graft (VFG) and massive allograft is considered a
      reliable method of treatment. However, little is known about the long-term
      outcome of this procedure. The aims of this study were to determine whether the
      morbidity of this procedure was comparable to that of other reconstructive
      techniques, if it was possible to achieve a satisfactory functional result, and
      whether biological reconstruction with a VFG and massive allograft could achieve
      a durable, long-lasting reconstruction. Patients and Methods: A total of 23
      patients with a mean age of 16 years (five to 40) who had undergone resection of
      an intercalary bone tumour of the femur and reconstruction with a VFG and
      allograft were reviewed clinically and radiologically. The mean follow-up was 141
      months (24 to 313). The mean length of the fibular graft was 18 cm (12 to 29).
      Full weight-bearing without a brace was allowed after a mean of 13 months (seven
      to 26). Results: At final follow-up, the mean Musculoskeletal Tumor Society Score
      of 22 evaluable patients was 94% (73 to 100). Eight major complications, five
      fractures (21.7%), and three nonunions (13%) were seen in seven patients (30.4%).
      Revision-free survival was 72.3% at five, ten, and 15 years, with fracture and
      nonunion needing surgery as failure endpoints. Overall survival, with removal of
      allograft or amputation as failure endpoints, was 94.4% at five, ten, and 15
      years. Discussion: There were no complications needing surgical revision after
      five years had elapsed from surgery, suggesting that the mechanical strength of
      the implant improves with time, thereby decreasing the risk of complications. In
      young patients with an intercalary bone tumour of the femur, combining a VFG and
      massive allograft may result in a reconstruction that lasts a lifetime. Cite this
      article: Bone Joint J 2018;100-B:378-86.

PMID- 29589496
TI  - Is tranexamic acid toxic to articular cartilage when administered topically?
AB  - Aims: The intra-articular administration of tranexamic acid (TXA) has been shown
      to be effective in reducing blood loss in unicompartmental knee arthroplasty and
      anterior cruciate reconstruction. The effects on human articular cartilage,
      however, remains unknown. Our aim, in this study, was to investigate any
      detrimental effect of TXA on chondrocytes, and to establish if there was a safe
      dose for its use in clinical practice. The hypothesis was that TXA would cause a
      dose-dependent damage to human articular cartilage. Materials and Methods: The
      cellular morphology, adhesion, metabolic activity, and viability of human
      chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length
      of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then
      repeated, excluding cellular adhesion, in a 3D model and confirmed in viable
      samples of articular cartilage. Results: Increasing concentrations above 20 mg/ml
      resulted in atypical morphology, reduced cellular adhesion and metabolic activity
      associated with increased chondrocyte death. However, the cell matrix was not
      affected by the concentration of TXA or the length of exposure, and offered
      cellular protection for concentrations below 20 mg/ml. Conclusion: These results
      show that when in vitro chondrocytes are exposed to higher concentrations of TXA,
      such as that expected following recommended intra-articular administration,
      cytotoxicity is observed. This effect is dose-dependent, such that a tissue
      concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this
      article: Bone Joint J 2018;100-B:404-12.

PMID- 29589495
TI  - Reverse shoulder arthroplasty for type 1 sequelae of a fracture of the proximal
      humerus.
AB  - Aims: The aim of this study was to analyze the results of reverse shoulder
      arthroplasty (RSA) in patients with type 1 sequelae of a fracture of the proximal
      humerus in association with rotator cuff deficiency or severe stiffness of the
      shoulder. Patients and Methods: A total of 38 patients were included: 28 women
      and ten men. Their mean age at the time of arthroplasty was 73 years (54 to 91).
      Before the RSA, 18 patients had been treated with open reduction and internal
      fixation following a fracture. A total of 22 patients had a rotator cuff tear and
      11 had severe stiffness of the shoulder with < 0 degrees  of external rotation.
      The mean follow-up was 4.3 years (1.5 to 10). The Constant score and the range of
      movement of the shoulder were recorded preoperatively and at final follow-up.
      Preoperatively, radiographs in two planes were performed, as well as CT or arthro
      CT scans; radiographs were also performed at final follow-up. Results: The mean
      Constant score improved from 25 points (5 to 47) preoperatively to 57 points (15
      to 81) postoperatively. The mean forward elevation of the shoulder increased from
      73 degrees  (10 degrees  to 130 degrees ) preoperatively to 117 degrees  (15
      degrees  to 170 degrees ) postoperatively. Previous surgery did not influence the
      outcome. Patients with rotator cuff tears had lower Constant scores than patients
      without (p = 0.037). Those with preoperative stiffness of the shoulder had lower
      postoperative external rotation compared with patients without stiffness (p =
      0.046). There was no radiographic evidence of loosening. Three complications
      occurred, leading to revision surgery in two patients. In all, 17 patients rated
      their result as very good (45%), another 17 as good (45%), two as satisfactory
      (5%), and two as unsatisfactory (5%). Discussion: RSA is an effective form of
      treatment for patients with type 1 sequelae of a fracture of the proximal humerus
      associated with rotator cuff deficiency or stiffness of the shoulder, with high
      rates of satisfaction. Rotator cuff tears and stiffness of the shoulder had an
      adverse effect on the clinical outcome. Cite this article: Bone Joint J 2018;100
      B:318-23.

PMID- 29589497
TI  - Risk factors for recurrent instability or revision surgery following arthroscopic
      Bankart repair.
AB  - Aims: The factors that predispose to recurrent instability and revision
      stabilization procedures after arthroscopic Bankart repair for anterior
      glenohumeral instability remain unclear. We sought to determine the rate and risk
      factors associated with ongoing instability in patients undergoing arthroscopic
      Bankart repair for instability of the shoulder. Materials and Methods: We used
      the Statewide Planning and Research Cooperative System (SPARCS) database to
      identify patients with a diagnosis of anterior instability of the shoulder
      undergoing arthroscopic Bankart repair between 2003 and 2011. Patients were
      followed for a minimum of three years. Baseline demographics and subsequent
      further surgery to the ipsilateral shoulder were analyzed. Multivariate analysis
      was used to identify independent risk factors for recurrent instability. Results:
      A total of 5719 patients were analyzed. Their mean age was 24.9 years (sd 9.3);
      4013 (70.2%) were male. A total of 461 (8.1%) underwent a further procedure
      involving the ipsilateral shoulder at a mean of 31.5 months (sd 23.8)
      postoperatively; 117 (2.1%) had a closed reduction and 344 (6.0%) had further
      surgery. Revision arthroscopic Bankart repair was the most common subsequent
      surgical procedure (223; 65.4%). Independent risk factors for recurrent
      instability were: age < 19 years (odds ratio 1.86), Caucasian ethnicity (hazard
      ratio 1.42), bilateral instability of the shoulder (hazard ratio 2.17), and a
      history of closed reduction(s) prior to the initial repair (hazard ratio 2.45).
      Revision arthroscopic Bankart repair was associated with significantly higher
      rates of ongoing persistent instability than revision open stabilization (12.4%
      vs 5.1%, p = 0.041). Conclusion: The incidence of a further procedure being
      required in patients undergoing arthroscopic Bankart repair for anterior
      glenohumeral instability was 8.1%. Younger age, Caucasian race, bilateral
      instability, and closed reduction prior to the initial repair were independent
      risk factors for recurrent instability, while subsequent revision arthroscopic
      Bankart repair had significantly higher rates of persistent instability than
      subsequent open revision procedures. Cite this article: Bone Joint J 2018;100
      B:324-30.

PMID- 29589498
TI  - The use of a non-invasive extendable prosthesis at the time of revision
      arthroplasty.
AB  - Aims: The use of a noninvasive growing endoprosthesis in the management of
      primary bone tumours in children is well established. However, the efficacy of
      such a prosthesis in those requiring a revision procedure has yet to be
      established. The aim of this series was to present our results using extendable
      prostheses for the revision of previous endoprostheses. Patients and Methods: All
      patients who had a noninvasive growing endoprosthesis inserted at the time of a
      revision procedure were identified from our database. A total of 21 patients
      (seven female patients, 14 male) with a mean age of 20.4 years (10 to 41) at the
      time of revision were included. The indications for revision were mechanical
      failure, trauma or infection with a residual leg-length discrepancy. The mean
      follow-up was 70 months (17 to 128). The mean shortening prior to revision was 44
      mm (10 to 100). Lengthening was performed in all but one patient with a mean
      lengthening of 51 mm (5 to 140). Results: The mean residual leg length
      discrepancy at final follow-up of 15 mm (1 to 35). Two patients developed a deep
      periprosthetic infection, of whom one required amputation to eradicate the
      infection; the other required two-stage revision. Implant survival according to
      Henderson criteria was 86% at two years and 72% at five years. When considering
      revision for any cause (including revision of the growing prosthesis to a non
      growing prosthesis), revision-free implant survival was 75% at two years, but
      reduced to 55% at five years. Conclusion: Our experience indicates that revision
      surgery using a noninvasive growing endoprosthesis is a successful option for
      improving leg length discrepancy and should be considered in patients with
      significant leg-length discrepancy requiring a revision procedure. Cite this
      article: Bone Joint J 2018;100-B:370-7.

PMID- 29589499
TI  - Teres major tendon transfer in the treatment of irreparable posterosuperior
      rotator cuff tears.
AB  - Aims: Since long-term outcome of teres major tendon transfer surgery for
      irreparable posterosuperior rotator cuff (RC) tears is largely unknown, the
      primary aim of this study was to evaluate the long-term outcome of the teres
      major transfer. We also aimed to report on the results of a cohort of patients
      with a similar indication for surgery that underwent a latissimus dorsi tendon
      transfer. Patients and Methods: Patients and Methods In this prospective cohort
      study, we reported on the long-term results of 20 consecutive patients with a
      teres major tendon transfer for irreparable massive posterosuperior RC tears.
      Additionally, we reported on the results of the latissimus dorsi tendon transfer
      (n = 19). The mean age was 60 years (47 to 77). Outcomes included the Constant
      score (CS), and pain at rest and during movement using the Visual Analogue Scale
      (VAS). Results: At a mean of ten years (8 to 12) following teres major transfer,
      the CS was still 23 points (95% confidence interval (CI) 14.6 to 30.9, p < 0.001)
      higher than preoperatively. VAS for pain at rest (21 mm, 95% CI 4.0 to 38.9, p =
      0.016) and movement (31 mm, 95% CI 16.0 to 45.1, p < 0.001) were lower than
      preoperatively. We also found an increase in CS (32 points, 95% CI 23.4 to 40.2,
      p < 0.001) and reduction of pain (26 mm, 95% CI 9.9 to 41.8, p = 0.001) six years
      after latissimus dorsi transfer. Conclusion: Teres major tendon transfer is a
      treatment option to gain shoulder function and reduce pain in patients with an
      irreparable posterosuperior RC tear at a mean follow-up of ten years. The teres
      major tendon might be a valuable alternative to the commonly performed latissimus
      dorsi tendon transfer in the treatment of irreparable posterosuperior RC tears.
      Cite this article: Bone Joint J 2018;100-B:309-17.

PMID- 29589500
TI  - The effect of triclosan-coated sutures on the rate of surgical site infection
      after hip and knee arthroplasty: a double-blind randomized controlled trial of
      2546 patients.
AB  - Aims: Surgical site infection (SSI) is a common complication of surgery with an
      incidence of about 1% in the United Kingdom. Sutures can lead to the development
      of a SSI, as micro-organisms can colonize the suture as it is implanted.
      Triclosan-coated sutures, being antimicrobical, were developed to reduce the rate
      of SSI. Our aim was to assess whether triclosan-coated sutures cause a reduction
      in SSIs following arthroplasty of the hip and knee. Patients and Methods: This
      two-arm, parallel, double-blinded study involved 2546 patients undergoing
      elective total hip (THA) and total knee arthroplasty (TKA) at three hospitals. A
      total of 1323 were quasi-randomized to a standard suture group, and 1223 being
      quasi-randomized to the triclosan-coated suture group. The primary endpoint was
      the rate of SSI at 30 days postoperatively. Results: The baseline characteristics
      of age, gender and comorbidities were well matched in the two groups. The rates
      of superficial SSI were 0.8% in the control group and 0.7% in the intervention
      group (p = 0.651), and when deep and superficial SSIs were combined the rates
      were 2.5% and 1.8 (p = 0.266). The length of stay in hospital and the rates of
      medical complications did not differ significantly between the groups (p =
      1.000). Conclusion: This trial provided no evidence that the use of triclosan
      coated sutures at THA and TKA leads to a reduction in the rate of SSI. Cite this
      article: Bone Joint J 2018;100-B:296-302.

PMID- 29589501
TI  - Glenoid osteotomy for atraumatic posteroinferior shoulder instability associated
      with glenoid dysplasia.
AB  - Aims: We report the clinical results of glenoid osteotomy in patients with
      atraumatic posteroinferior instability associated with glenoid dysplasia.
      Patients and Methods: The study reports results in 211 patients (249 shoulders)
      with atraumatic posteroinferior instability. The patients comprised 63 men and
      148 women with a mean age of 20 years. The posteroinferior glenoid surface was
      elevated by osteotomy at the scapular neck. A body spica was applied to maintain
      the arm perpendicular to the glenoid for two weeks postoperatively. Clinical
      results were evaluated using the Rowe score and Japan Shoulder Society Shoulder
      Instability Score (JSS-SIS); bone union, osteoarthrosis, and articular congruity
      were examined on plain radiographs. Results: The Rowe score improved from 36 to
      88 points, and the JSS-SIS improved from 47 to 81 points. All shoulders exhibited
      union without progression of osteoarthritis except one shoulder, which showed
      osteoarthritic change due to a previous surgery before the glenoid osteotomy. All
      but three shoulders showed improvement in joint congruency. Eight patients
      developed disordered scapulohumeral rhythm during arm elevation, and 12 patients
      required additional open stabilization for anterior instability. Conclusion: Good
      results can be expected from glenoid osteotomy in patients with atraumatic
      posteroinferior instability associated with glenoid dysplasia. Cite this article:
      Bone Joint J 2018;100-B:331-7.

PMID- 29589502
TI  - Comparison between a multicentre, collaborative, closed-loop audit assessing
      management of supracondylar fractures and the British Orthopaedic Association
      Standard for Trauma 11 (BOAST 11) guidelines.
AB  - Aims: Supracondylar fractures are the most frequently occurring paediatric
      fractures about the elbow and may be associated with a neurovascular injury. The
      British Orthopaedic Association Standards for Trauma 11 (BOAST 11) guidelines
      describe best practice for supracondylar fracture management. This study aimed to
      assess whether emergency departments in the United Kingdom adhere to BOAST 11
      standard 1: a documented assessment, performed on presentation, must include the
      status of the radial pulse, digital capillary refill time, and the individual
      function of the radial, median (including the anterior interosseous), and ulnar
      nerves. Materials and Methods: Stage 1: We conducted a multicentre, retrospective
      audit of adherence to BOAST 11 standard 1. Data were collected from eight
      hospitals in the United Kingdom. A total of 433 children with Gartland type 2 or
      3 supracondylar fractures were eligible for inclusion. A centrally created data
      collection sheet was used to guide objective analysis of whether BOAST 11
      standard 1 was adhered to. Stage 2: We created a quality improvement proforma for
      use in emergency departments. This was piloted in one of the hospitals used in
      the primary audit and was re-audited using equivalent methodology. In all, 102
      patients presenting between January 2016 and July 2017 were eligible for
      inclusion in the re-audit. Results: Stage 1: Of 433 patient notes audited,
      adherence to BOAST 11 standard 1 was between 201 (46%) and 232 (54%) for the
      motor and sensory function of the individual nerves specified, 318 (73%) for
      radial pulse, and 247 (57%) for digital capillary refill time. Stage 2: Of 102
      patient notes audited, adherence to BOAST 11 standard 1 improved to between 72
      (71%) and 80 (78%) for motor and sensory function of the nerves, to 84 (82%) for
      radial pulse, and to 82 (80%) for digital capillary refill time. Of the 102 case
      notes reviewed in stage 2, only 44 (43%) used the quality improvement proforma;
      when the proforma was used, adherence improved to between 40 (91%) and 43 (98%)
      throughout. Conclusion: Adherence to BOAST 11 standard 1 is poor in hospitals
      across the country. This is concerning as neurovascular deficit may be an
      indication for emergent surgery, and missed neurovascular injury can cause long
      term, or even permanent, functional impairment. We present a simple proforma that
      improves adherence to this standard, can easily be implemented into emergency
      departments, and may improve patient safety. Cite this article: Bone Joint J
      2018;100-B:346-51.

PMID- 29589503
TI  - Treatment and functional outcomes of complex tibial fractures in children and
      adolescents using the Ilizarov method.
AB  - Aims: The aim of this study was to report the clinical, functional and
      radiological outcomes of children and adolescents with tibial fractures treated
      using the Ilizarov method. Patients and Methods: Between 2013 and 2016 a total of
      74 children with 75 tibial fractures underwent treatment at our major trauma
      centre using an Ilizarov frame. Demographic and clinical information from a
      prospective database was supplemented by routine functional and psychological
      assessment and a retrospective review of the notes and radiographs. Results: Of
      the 75 fractures, 26 (35%) were open injuries, of which six (8%) had segmental
      bone loss. There were associated physeal injuries in 18 (24%), and 12 (16%)
      involved conversion of treatment following failure of previous management. The
      remaining children had a closed unstable fracture or significant soft-tissue
      compromise. The median follow-up was 16 months (7 to 31). All fractures united
      with a median duration in a frame of 3.6 months (interquartile range 3.1 to 4.6);
      there was no significant difference between the types of fracture and the
      demographics of the patients. There were no serious complications and no
      secondary procedures were required to achieve union. Health-related quality of
      life measures were available for 60 patients (80%) at a minimum of six months
      after removal of the frame. These indicated a good return to function (median
      Paediatric quality of life score, 88.0; interquartile range 70.3 to 100).
      Conclusion: The Ilizarov method is a safe, effective and reliable method for the
      treatment of complex paediatric tibial fractures. Cite this article: Bone Joint J
      2018;100-B:396-403.

PMID- 29589504
TI  - Long-term results of the lateral resurfacing elbow arthroplasty.
AB  - Aims: The aim of this study was to report the long-term outcome and implant
      survival of the lateral resurfacing elbow (LRE) arthroplasty in the treatment of
      elbow arthritis. Patients and Methods: We reviewed a consecutive series of 27
      patients (30 elbows) who underwent LRE arthroplasty between December 2005 and
      January 2008. There were 15 women and 12 men, with a mean age of 61 years (25 to
      82). The diagnosis was primary hypotrophic osteoarthritis (OA) in 12 patients (14
      elbows), post-traumatic osteoarthritis (PTOA) in five (five elbows) and
      rheumatoid arthritis (RA) in ten patients (11 elbows). The mean clinical outcome
      scores including the Mayo Elbow Performance Score (MEPS), the American Shoulder
      and Elbow Surgeons elbow score (ASES-e), the mean range of movement and the
      radiological outcome were recorded at three, six and 12 months and at a mean
      final follow-up of 8.3 years (7.3 to 9.4). A one sample t-test comparing pre and
      postoperative values, and survival analysis using the Kaplan-Meier method were
      undertaken. Results: A statistically significantly increased outcome score was
      noted for the whole group at each time interval. This was also significantly
      increased at each time in each of the subgroups (OA, RA, and PTOA). Implant
      survivorship was 100%. Conclusion: We found that the LRE arthroplasty, which was
      initially developed for younger patients with osteoarthritis, is an effective
      form of surgical treatment for a wider range of patients with more severe
      degenerative changes, irrespective of their cause. It is therefore a satisfactory
      alternative to total elbow arthroplasty (TEA) and has lower rates of
      complications in the subgroups of patients we have studied. It does not require
      activities to be restricted to the same extent as following TEA. Based on this
      experience, we now recommend LRE arthroplasty rather than TEA as the primary form
      of implant for the treatment of patients with OA of the elbow. Cite this article:
      Bone Joint J 2018;100-B:338-45.

PMID- 29589490
TI  - Factors associated with health-related quality of life, hip function, and health
      utility after operative management of femoral neck fractures.
AB  - Aims: The primary aim of this prognostic study was to identify baseline factors
      associated with physical health-related quality of life (HRQL) in patients after
      a femoral neck fracture. The secondary aims were to identify baseline factors
      associated with mental HRQL, hip function, and health utility. Patients and
      Methods: Patients who were enrolled in the Fixation using Alternative Implants
      for the Treatment of Hip Fractures (FAITH) trial completed the 12-item Short Form
      Health Survey (SF-12), Western Ontario and McMaster Universities Arthritis Index,
      and EuroQol 5-Dimension at regular intervals for 24 months. We conducted
      multilevel mixed models to identify factors potentially associated with HRQL.
      Results: The following were associated with lower physical HRQL: older age (-1.42
      for every ten-year increase, 95% confidence interval (CI) -2.17 to -0.67, p <
      0.001); female gender (-1.52, 95% CI -3.00 to -0.05, p = 0.04); higher body mass
      index (-0.69 for every five-point increase, 95% CI -1.36 to -0.02, p = 0.04);
      American Society of Anesthesiologists class III ( versus class I) (-3.19, 95% CI 
      5.73 to -0.66, p = 0.01); and sustaining a displaced fracture (-2.18, 95% CI 
      3.88 to -0.49, p = 0.01). Additional factors were associated with mental HRQL,
      hip function, and health utility. Conclusion: We identified several baseline
      factors associated with lower HRQL, hip function, and utility after a femoral
      neck fracture. These findings may be used by clinicians to inform treatment and
      outcomes. Cite this article: Bone Joint J 2018;100-B:361-9.

PMID- 29589505
TI  - Biological augmentation of graft healing in anterior cruciate ligament
      reconstruction.
AB  - Aims: The success of anterior cruciate ligament reconstruction (ACLR) depends on
      osseointegration at the graft-tunnel interface and intra-articular
      ligamentization. Our aim was to conduct a systematic review of clinical and
      preclinical studies that evaluated biological augmentation of graft healing in
      ACLR. Materials and Methods: In all, 1879 studies were identified across three
      databases. Following assessment against strict criteria, 112 studies were
      included (20 clinical studies; 92 animal studies). Results: Seven categories of
      biological interventions were identified: growth factors, biomaterials, stem
      cells, gene therapy, autologous tissue, biophysical/environmental, and
      pharmaceuticals. The methodological quality of animal studies was moderate in
      97%, but only 10% used clinically relevant outcome measures. The most
      interventions in clinical trials target the graft-tunnel interface and are
      applied intraoperatively. Platelet-rich plasma is the most studied intervention,
      but the clinical outcomes are mixed, and the methodological quality of studies
      was suboptimal. Other biological therapies investigated in clinical trials
      include: remnant-augmented ACLR; bone substitutes; calcium phosphate-hybridized
      grafts; extracorporeal shockwave therapy; and adult autologus non-cultivated stem
      cells. Conclusion: There is extensive preclinical research supporting the use of
      biological therapies to augment ACLR. Further clinical studies that meet the
      minimum standards of reporting are required to determine whether emerging
      biological strategies will provide tangible benefits in patients undergoing ACLR.
      Cite this article: Bone Joint J 2018;100-B:271-84.

PMID- 29589506
TI  - The future of ACL reconstruction is more than tunnels and grafts.

PMID- 29589507
TI  - Development, content validity and test-retest reliability of the Lifelong
      Physical Activity Skills Battery in adolescents.
AB  - Numerous skill batteries assess fundamental motor skill (e.g., kick, hop)
      competence. Few skill batteries examine lifelong physical activity skill
      competence (e.g., resistance training). This study aimed to develop and assess
      the content validity, test-retest and inter-rater reliability of the "Lifelong
      Physical Activity Skills Battery". Development of the skill battery occurred in
      three stages: i) systematic reviews of lifelong physical activity participation
      rates and existing motor skill assessment tools, ii) practitioner consultation
      and iii) research expert consultation. The final battery included eight skills:
      grapevine, golf swing, jog, push-up, squat, tennis forehand, upward dog and
      warrior I. Adolescents (28 boys, 29 girls; M = 15.8 years, SD = 0.4 years)
      completed the Lifelong Physical Activity Skills Battery on two occasions two
      weeks apart. The skill battery was highly reliable (ICC = 0.84, 95% CI = 0.72
      0.90) with individual skill reliability scores ranging from moderate (warrior I;
      ICC = 0.56) to high (tennis forehand; ICC = 0.82). Typical error (4.0; 95% CI 3.4
      5.0) and proportional bias (r = -0.21, p = .323) were low. This study has
      provided preliminary evidence for the content validity and reliability of the
      Lifelong Physical Activity Skills Battery in an adolescent population.

PMID- 29589508
TI  - A Longitudinal Analysis of the Relationships of Physical Activity and Body Fat
      With Nerve Growth Factor and Brain-Derived Neural Factor in Children.
AB  - BACKGROUND: Nerve growth factor (NGF) and brain-derived neural factor (BDNF) are
      important for brain function and detectable in the blood. This study explored the
      longitudinal associations of physical activity and body fat with serum NGF and
      BDNF in children. METHODS: Two waves of measurements were performed 2 years apart
      in 8- to 11-year-old children, including physical activity using the ActiGraph
      model 7164, body composition by dual-energy X-ray absorptiometry, and serum NGF
      and BDNF determined by multiplex immunoassay. The first wave included 248
      children. Full information maximum likelihood estimation with robust standard
      errors was applied in structural equation modeling. RESULTS: Vigorous physical
      activity showed a direct positive longitudinal relationship with NGF
      (standardized coefficient beta = 0.30, P = .01) but not with BDNF (beta = 0.04, P
      = .84). At the same time, body fat percentage was positively related to both NGF
      (beta = 0.59, P < .001) and BDNF (beta = 0.17, P = .04). There was an indication
      of an indirect relationship of vigorous physical activity with NGF (product of
      unstandardized coefficient beta = -0.18, P = .02) and BDNF (beta = -0.07, P =
      .05) through the negative relationship with body fat percentage (beta = -0.36, P
      < .001). CONCLUSIONS: Vigorous physical activity is directly related to serum NGF
      and indirectly through the level of body fat. The relationships with serum BDNF
      are more complex.

PMID- 29589509
TI  - Walking, But Not Other Physical Activity at a Higher Intensity, Is Associated
      With Improved Kidney Function: A Cross-Sectional Health Survey of General Adult
      Population.
AB  - BACKGROUND: Chronic kidney disease is common and brings significant health
      burden. The purpose of this study was to investigate the relationship between
      physical activity and kidney function. METHODS: This was a cross-sectional study
      set in the Nanjing Community Cardiovascular Risk Survey, using random cluster
      sampling. Questionnaires were completed, wherever possible, through face-to-face
      interviews. Data on age, sex, body mass index, weekly physical activity, and
      kidney function were collected. Physical activity was measured by the metabolic
      equivalent of task-minutes per week and grouped into "walking," "moderate," and
      "vigorous" according to intensity. Kidney function was measured by the estimated
      glomerular filtration rate (eGFR, in mL/min/1.73 m2). Regression modeling was
      used to investigate the proposed relationship with adjustment for other
      confounding factors. RESULTS: A total of 5824 participants were included, with an
      average age of 52; 44% were male. The eGFR in average was 76 mL/min/1.73 m2, with
      19% >= 90, 67% between 60 and 89, and 14% < 60. In average, the total physical
      activity during a week was 3644 MET-minutes per week. Moderate activity
      contributed 64% of the total activity, followed by walking (23%) and vigorous
      activity (13%). Overall, the total activity was weakly associated with eGFR (P =
      .039). However, in stratified analysis, only walking-related activity was
      associated with eGFR (P < .0001) after confounding adjustment. CONCLUSIONS:
      Walking is associated with improved kidney function.

PMID- 29589510
TI  - How to handle gene drives in arthropods?

PMID- 29589511
TI  - Circadian Rhythms and Reproductive Phenology Covary in a Natural Plant
      Population.
AB  - The circadian clock is a molecular timekeeper that matches endogenous rhythms in
      diverse traits with 24-h cycles in the external environment. Although a lack of
      clock resonance to the environment is detrimental to performance, clock
      phenotypes in wild populations nevertheless deviate substantially from the
      predicted optimal cycle length of 24 h, and significant genetic variation exists
      for circadian parameters. Here, we describe covariation between 2 traits
      considered to reflect adaptation to different aspects of temporal environmental
      heterogeneity, circadian rhythms (adaptation to daily environmental cycles) and
      flowering time (adaptation to seasonal cycles), in a Rocky Mountain population of
      the mustard Boechera stricta, a North American relative of Arabidopsis thaliana.
      We found that 18 families that differ in circadian period in leaf movement by 3.5
      h expressed genetic diversity in first-year growth, reproductive phenology,
      vegetative size at reproduction, and starch concentration following
      vernalization. The families exhibited a large (~90-day) range in mean flowering
      time, even though the spatial scale of population sampling covered only a few
      hundred meters. Circadian period covaried with other traits such that longer
      period families flowered earlier and at a larger size, a trait combination
      predicted to yield a fitness benefit in the wild. Circadian clock research in
      model systems has previously shown that mutations in clock genes influence
      phenology. Our results widen the scope of this research by illustrating a link
      between naturally segregating clock variation and reproductive phenology among
      wild genotypes, suggesting that the causes of genetic diversity in the clock lie
      partly in adaptation to seasonal environmental heterogeneity.

PMID- 29589512
TI  - Non-communicable diseases in Indian slums: re-framing the Social Determinants of
      Health.
AB  - BACKGROUND: The epidemic of non-communicable diseases (NCDs) in slums has pushed
      its residents to heightened vulnerability. The Social Determinants of Health
      (SDH) framework has been used to understand the social dynamics and impact of
      NCDs, especially in poorly resourced communities. Whilst the SDH has helped to
      discredit the characterisation of NCDs as diseases of affluence, its impact on
      policy has been less definite. Given the multitude of factors that interact in
      the presentation of NCDs, operationalising the SDH for policies and programmes
      that account for the contextual complexity of slums has stalled. OBJECTIVE: To
      organise the complex networks of relations between SDH in slums so as to identify
      options for Indian municipal policy that are feasible to implement in the short
      term. METHODS: The study reviews the literature describing SDH in Indian slums,
      specifically those that establish causal relations between SDH and NCDs. Root
      cause analysis was then used to organise the identified relations of SDH and
      NCDs. RESULTS: Although poverty remains the largest structural determinant of
      health in slums, the multi-dimensional relations between SDH and NCDs are
      structured around four themes that describe the dynamics of slums, namely scarce
      clean water, low education, physical (in)activity and transportation. From the
      reviewed literature, four logic trees visualising the relations between SDH in
      slums and NCDs were constructed. The logic trees separate symptomatic problems
      from their more distal causes, and recommendations were formulated based on
      features of these relationships that are amenable to policy intervention.
      CONCLUSION: Root cause analysis provides a means to focus the lens of examination
      of SDH, as evidenced here for Indian slums. It provides a guide for the
      development of policies that are grounded in the actual health concerns of people
      in slums, and takes account of the complex pathways through which diseases are
      socially constituted.

PMID- 29589514
TI  - Board Walk - April 2018.

PMID- 29589513
TI  - X-ray crystallography of TRP channels.
AB  - Transient receptor potential (TRP) ion channels are molecular sensors of a large
      variety of stimuli including temperature, mechanical stress, voltage, small
      molecules including capsaicin and menthol, and lipids such as
      phosphatidylinositol 4,5-bisphosphate (PIP2). Since the same TRP channels may
      respond to different physical and chemical stimuli, they can serve as signal
      integrators. Many TRP channels are calcium permeable and contribute to Ca2+
      homeostasis and signaling. Although the TRP channel family was discovered decades
      ago, only recently have the structures of many of these channels been solved,
      largely by cryo-electron microscopy (cryo-EM). Complimentary to cryo-EM, X-ray
      crystallography provides unique tools to unambiguously identify specific atoms
      and can be used to study ion binding in channel pores. In this review we describe
      crystallographic studies of the TRP channel TRPV6. The methodology used in these
      studies may serve as a template for future structural analyses of different types
      of TRP and other ion channels.

PMID- 29589515
TI  - Rheolytic effects of left main mid-shaft/distal stenting: a computational flow
      dynamic analysis.
AB  - Background The aim of this study was to evaluate the rheolytic effects of
      stenting a mid-shaft/distal left main coronary artery (LMCA) lesion with and
      without ostial coverage. Stenting of the LMCA has emerged as a valid alternative
      in place of traditional coronary bypass graft surgery. However, in case of mid
      shaft/distal lesion, there is no consensus regarding the extension of the strut
      coverage up to the ostium or to stent only the culprit lesion. Methods We
      reconstructed a left main-left descending coronary artery (LM-LCA)-left
      circumflex (LCX) bifurcation after analysing 100 consecutive patients (mean age
      71.4 +/- 9.3, 49 males) with LM mid-shaft/distal disease. The mean diameter of
      proximal LM, left anterior descending (LAD) and LCX, evaluated with quantitative
      coronary angiography (QCA) was 4.62 +/- 0.86 mm, 3.31 +/- 0.92 mm, and 2.74 +/-
      0.93 mm, respectively. For the stent simulation, a third-generation, everolimus
      eluting stent was virtually reconstructed. Results After virtual stenting, the
      net area averaged wall shear stress (WSS) of the model and the WSS at the LCA-LCX
      bifurcation resulted higher when the stent covered the culprit mid-shaft lesion
      only compared with the extension of the stent covering the ostium (3.68 versus
      2.06 Pa, p = 0.01 and 3.97 versus 1.98 Pa, p < 0.001, respectively. Similarly,
      the static pressure and the Reynolds number were significantly higher after stent
      implantation covering up the ostium. At the ostium, the flow resulted more
      laminar when stenting only the mid-shaft lesion than including the ostium.
      Conclusions Although these findings cannot be translated directly into real
      practice our brief study suggests that stenting lesion 1:1 or extending the stent
      to cover the LM ostium impacts differently the rheolytic properties of LMCA
      bifurcation with potential insights for restenosis or thrombosis.

PMID- 29589516
TI  - Upgrading pyrolytic residue from waste tires to commercial carbon black.
AB  - The managing and recycling of waste tires has become a worldwide environmental
      challenge. Among the different disposal methods for waste tires, pyrolysis is
      regarded as a promising route. How to effectively enhance the added value of
      pyrolytic residue (PR) from waste tires is a matter of great concern. In this
      study, the PRs were treated with hydrochloric and hydrofluoric acids in turn
      under ultrasonic waves. The removal efficiency for the ash and sulfur was
      investigated. The pyrolytic carbon black (PCB) obtained after treating PR with
      acids was analyzed by X-ray fluorescence spectrophotometry, Fourier transform
      infrared spectrometry, X-ray diffractometry, laser Raman spectrometry, scanning
      electron microscopy, thermogravimetric (TG) analysis, and physisorption
      apparatus. The properties of PCB were compared with those of commercial carbon
      black (CCB) N326 and N339. Results showed PRs from waste tires were mainly
      composed of carbon, sulfur, and ash. The carbon in PCB was mainly from the CCB
      added during tire manufacture rather than from the pyrolysis of pure rubbers. The
      removal percentages for the ash and sulfur of PR are 98.33% (from 13.98 wt % down
      to 0.24 wt %) and 70.16% (from 1.81 wt % down to 0.54 wt %), respectively, in the
      entire process. The ash was mainly composed of metal oxides, sulfides, and
      silica. The surface properties, porosity, and morphology of the PCB were all
      close to those of N326. Therefore, PCB will be a potential alternative of N326
      and reused in tire manufacture. This route successfully upgrades PR from waste
      tires to the high value-added CCB and greatly increases the overall efficiency of
      the waste tire pyrolysis industry.

PMID- 29589517
TI  - Door-to-door recyclables collection programmes: Willingness to participate and
      influential factors with a case study in the city of Xanthi (Greece).
AB  - The implementation of a recyclable waste management system is a serious challenge
      for a society that aims to contribute to sustainability. The first operational
      step of such system is waste collection. In a number of European countries, the
      solid waste collection system has changed from the conventional kerbside system
      to a door-to-door collection. However, this type of waste collection system has
      not yet been introduced in Greece and its public acceptance prior to potential
      full implementation needs to be considered. This study aims to investigate the
      willingness of the residents of a Greek city (Xanthi, Thrace) to change from the
      existing kerbside collection system and initiate and participate in a door-to
      door recyclable waste collection system instead. A questionnaire was designed and
      distributed randomly to 150 residents of Xanthi and a statistical analysis was
      then performed to assess the influence of a number of explanatory variables on
      recycling behaviour and the willingness to participate in a door-to-door
      collection system. The findings of this study indicate that most of the
      respondents (72.7%) were willing to participate in a future door-to-door
      recyclables collection programme in Xanthi. The factors that influenced the
      respondents' attitude with regard to such a programme were associated with level
      of education, their beliefs about the effectiveness of the current recycling
      system and also their attitudes towards recycling issues in general. Age and
      religion significantly affected recycling frequency. The survey and statistics
      presented in this article can be used as a model to assess the behaviour of
      citizens towards recyclable waste management systems worldwide.

PMID- 29589518
TI  - Effects of different frequencies of repetitive transcranial magnetic stimulation
      in stroke patients with non-fluent aphasia: a randomized, sham-controlled study.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of repetitive
      transcranial magnetic stimulation (rTMS) applied at different frequencies to the
      contra-lesional hemisphere to optimize the treatment of post-stroke non-fluent
      aphasia. METHOD: Patients with post-stroke non-fluent aphasia were divided
      randomly into four groups: a high-frequency rTMS (HF-rTMS) group (10 Hz), a low
      frequency rTMS (LF-rTMS) group (1 Hz), a sham stimulation group, and a control
      group. All groups received the standard treatment (consisting of drug therapy,
      conventional physical exercises, and speech training); in the HF-rTMS and LF
      rTMS, this was supplemented with magnetic stimulation that targeted the mirror
      area within the right hemispheric Broca's area. Patients' language ability was
      assessed prior to, immediately after, and at 2 months post-treatment by the
      Chinese version of the Western Aphasia Battery (WAB). RESULTS: When measured
      immediately post-treatment, as well as at 2 months post-treatment, the LF-rTMS
      group exhibited a more marked improvement than the HF-rTMS group in spontaneous
      speech, auditory comprehension, and aphasia quotients (AQ). Compared to the
      control group, the HF-rTMS cohort exhibited significant improvement at 2-months
      post-treatment in repetition and AQ. CONCLUSIONS: LF-rTMS and HF-rTMS are both
      beneficial to the recovery of linguistic function in patients with post-stroke
      non-fluent aphasia. LF-rTMS produced immediate benefits that persisted long-term,
      while HF-rTMS only produced long-term benefits. In addition, the benefits
      produced with LF-rTMS were more marked than those produced by HF-rTMS.

PMID- 29589520
TI  - Insomnia, Posttraumatic Stress Disorder Symptoms, and Danger: Their Impact on
      Victims' Return to Court for Orders of Protection.
AB  - The linkages between intimate partner violence (IPV), posttraumatic stress
      disorder (PTSD), and insomnia have been the subject of inquiry. This study is the
      first to explore the associations between clinical-level insomnia, PTSD symptoms,
      danger, and victim socio-demographics, and whether IPV victims pursue permanent
      orders of protection (OPs). Data for this secondary analysis were collected
      through surveys, interviews, and reviews of court records on 112 women who
      resided in upstate New York. Women initiated actions to obtain OPs from the
      Domestic Violence Intensive Intervention Court (DVIIC), from 2007 to 2008. The
      following factors were analyzed to determine their impact on whether a woman
      returned to court: (a) age, (b) race, (c) employment status, (d) perceived
      danger, (e) PTSD symptoms, and (f) clinical-level insomnia. This study finds that
      the following factors significantly relate to return to court: race, clinical
      level insomnia and perceived danger, clinical-level insomnia and PTSD symptoms,
      and severe danger level. However, in the final multivariate logistic regression,
      only race emerged as a predictor of whether a woman returned to court.
      Specifically, women of color were a third less likely to return to court than
      White women. These results have significant implications for future research and
      clinical intervention.

PMID- 29589521
TI  - Grief and Solidarity Reactions 1 Week After an On-Campus Shooting.
AB  - The impact of interpersonal violence extends beyond the victims and
      perpetrator(s). The purpose of this research was threefold: (a) to identify
      whether college students' very early reactions to an on-campus shooting were
      associated with well-known predictors of distress, (b) to examine whether grief
      and distress reactions were distinguishable in the early days following a
      shooting, and (c) to investigate whether a compassionate self-identity was
      uniquely associated with grief but not distress. Beginning just 3 days after an
      early morning shooting that killed one student and injured three others,
      university students ( N = 408) completed an online questionnaire. Grief, but not
      distress, was associated with a sense of solidarity with other students and a
      compassionate self-identity. General distress was associated with prior mental
      health difficulties and exposure to the shooting. Acute stress was positively
      associated with being female, having prior mental health difficulties, media
      exposure, perceived similarity to victims, less victim blame, social support, and
      social strain. Results suggest that grief reactions that arise in the early days
      following a collective loss may serve as important psychosocial resources in
      coping with interpersonal violence.

PMID- 29589519
TI  - Dopamine-mediated calcium channel regulation in synaptic suppression in L.
      stagnalis interneurons.
AB  - D2 dopamine receptor-mediated suppression of synaptic transmission from
      interneurons plays a key role in neurobiological functions across species,
      ranging from respiration to memory formation. In this study, we investigated the
      mechanisms of D2 receptor-dependent suppression using soma-soma synapse between
      respiratory interneuron VD4 and LPeD1 in the mollusk Lymnaea stagnalis (L.
      stagnalis). We studied the effects of dopamine on voltage-dependent Ca2+ current
      and synaptic vesicle release from the VD4. We report that dopamine inhibits
      voltage-dependent Ca2+ current in the VD4 by both voltage-dependent and 
      independent mechanisms. Dopamine also suppresses synaptic vesicle release
      downstream of activity-dependent Ca2+ influx. Our study demonstrated that
      dopamine acts through D2 receptors to inhibit interneuron synaptic transmission
      through both voltage-dependent Ca2+ channel-dependent and -independent pathways.
      Taken together, these findings expand our understanding of dopamine function and
      fundamental mechanisms that shape the dynamics of neural circuit.

PMID- 29589522
TI  - The Circadian Clock of the Ant Camponotus floridanus Is Localized in Dorsal and
      Lateral Neurons of the Brain.
AB  - The circadian clock of social insects has become a focal point of interest for
      research, as social insects show complex forms of timed behavior and organization
      within their colonies. These behaviors include brood care, nest maintenance,
      foraging, swarming, defense, and many other tasks, of which several require
      social synchronization and accurate timing. Ants of the genus Camponotus have
      been shown to display a variety of daily timed behaviors such as the emergence of
      males from the nest, foraging, and relocation of brood. Nevertheless, circadian
      rhythms of isolated individuals have been studied in few ant species, and the
      circadian clock network in the brain that governs such behaviors remains
      completely uncharacterized. Here we show that isolated minor workers of
      Camponotus floridanus exhibit temperature overcompensated free-running locomotor
      activity rhythms under constant darkness. Under light-dark cycles, most animals
      are active during day and night, with a slight preference for the night. On the
      neurobiological level, we show that distinct cell groups in the lateral and
      dorsal brain of minor workers of C. floridanus are immunostained with an antibody
      against the clock protein Period (PER) and a lateral group additionally with an
      antibody against the neuropeptide pigment-dispersing factor (PDF). PER abundance
      oscillates in a daily manner, and PDF-positive neurites invade most parts of the
      brain, suggesting that the PER/PDF-positive neurons are bona fide clock neurons
      that transfer rhythmic signals into the relevant brain areas controlling rhythmic
      behavior.

PMID- 29589523
TI  - An Update on JAK Inhibitors.
AB  - Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by
      four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different
      inflammatory and autoimmune diseases, as well as in malignancies, through the
      activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in
      JAK2 was identified in patients affected by myeloproliferative neoplasms. This
      knowledge prompted researchers from academia and pharmaceutical companies to
      investigate this field in order to discover small molecule JAK inhibitors. These
      efforts recently afforded to the market approval of four JAK inhibitors. Despite
      the fact that all these drugs are pyrrolo[2,3-d]pyrimidine derivatives, many
      compounds endowed with different heterocyclic scaffolds have been reported in the
      literature as selective or multi-JAK inhibitors, and a number of them is
      currently being evaluated in clinical trials. In this review we will report many
      representative compounds that have been published in articles or patents in the
      last five years (period 2013-2017). The inhibitors will be classified on the
      basis of their chemical structure, focusing, when possible, on their structure
      activity relationships, selectivity and biological activity. For every class of
      derivatives, compounds disclosed before 2013 that have entered clinical trials
      will also be briefly reported, to underline the importance of a particular
      chemical scaffold in the search for new inhibitors.

PMID- 29589524
TI  - ABC transporters in extrahepatic tissues: Pharmacological regulation in heart and
      intestine.
AB  - ATP binding cassette (ABC) transporters are transmembrane proteins expressed in
      secretory epithelia like the liver, kidneys and intestine, in epithelia
      exhibiting barrier function such as the blood-brain barrier and placenta, and to
      a much lesser extent, in tissues like reproductive organs, lungs, heart and
      pancreas, among others. They regulate internal distribution of endogenous
      metabolites and xenobiotics including drugs of therapeutic use and also
      participate in their elimination from the body. We here describe the function and
      regulation of ABC transporters in heart and small intestine, as examples of
      extrahepatic tissues, in which ABC proteins play clearly different roles. In
      heart, they are involved in tissue pathogenesis as well as in protecting this
      organ against toxic compounds and drug-induced oxidative stress. The small
      intestine is highly exposed to therapeutic drugs taken orally and, consequently,
      ABC transporters localized on its surface strongly influence drug absorption and
      pharmacokinetics. Examples of the ABC proteins currently described are Multidrug
      Resistance-associated Proteins 1 and 2 (MRP1 and 2) for heart and small
      intestine, respectively, and P-glycoprotein (P-gp) and Breast Cancer Resistance
      Protein (BCRP) for both organs.

PMID- 29589525
TI  - Impact of Dysfunctional Protein Catabolism on Macrophage Cholesterol Handling.
AB  - Protein catabolism in macrophages, which is accomplished mainly through autophagy
      lysosomal degradation, ubiquitin-proteasome system, and calpains, is disturbed in
      atheroprone vessels. Moreover, growing evidence suggests that defects in protein
      catabolism interfere with cholesterol handling in macrophages. Indeed, decreases
      in autophagy facilitate the deposition of cholesterol in atheroprone macrophages
      and the subsequent development of vulnerable atherosclerotic plaques due to
      impaired catabolism of lipid droplets and limited efferocytic clearance of deadly
      cells. The proteasome is responsible for the degradation of ATP-binding cassette
      transporters, which leads to impaired cholesterol efflux from macrophages.
      Overactivation of conventional calpains contributes to the excessive processing
      of functional proteins, thereby accelerating receptor-mediated uptake of oxidized
      low-density lipoproteins (LDLs) and slowing cholesterol efflux. Furthermore,
      calpain-6, an unconventional nonproteolytic calpain in macrophages, potentiates
      pinocytotic uptake of native LDL and attenuates the efferocytic clearance of
      deadly cells. Herein, we focus on recent progress in understanding how defective
      protein catabolism is associated with macrophage cholesterol handling and
      subsequent atherogenesis.

PMID- 29589526
TI  - ADAM metalloproteinases as potential drug targets.
AB  - The ADAMs, together with ADAMTSs and snake venom metalloproteases (SVMPs), are
      members of the Adamalysin family. Differences in structural organization,
      functions and localization are known and their domains, catalytic or non
      catalytic, show key roles in the substrate recognition and protease activity.
      Some ADAMs, as membrane-bound enzymes, show sheddase activity. Sheddases are key
      to modulation of functional proteins such as the tumor necrosis factor, growth
      factors, cytokines and their receptors, adhesion proteins, signaling molecules
      and stress molecules involved in immunity. These activities take part in the
      regulation of several physiological and pathological processes including
      inflammation, tumor growth, metastatic progression and infectious diseases. On
      these bases, some ADAMs are currently investigated as drug targets to develop new
      alternative therapies in many fields of medicine. This review will be focused on
      these aspects.

PMID- 29589527
TI  - Mechanism and Inhibition of Matrix Metalloproteinases.
AB  - Matrix metalloproteinases hydrolyze proteins and glycoproteins forming the
      extracellular matrix, cytokines and growth factors released in the extracellular
      space, and membrane-bound receptors on the outer cell membrane. The pathological
      relevance of MMPs has prompted the structural and functional characterization of
      these enzymes and the development of synthetic inhibitors as possible drug
      candidates. Recent studies have provided a better understanding of the substrate
      preference of the different members of the family, and structural data on the
      mechanism by which these enzymes hydrolyze the substrates. Here, we report the
      recent advancements in the understanding of the mechanism of collagenolysis and
      elastolysis, and we discuss the perspectives of new therapeutic strategies for
      targeting MMPs.

PMID- 29589528
TI  - Flavonols and flavones - protecting against myocardial ischemia/reperfusion
      injury by targeting protein kinases.
AB  - In acute myocardial infarction (AMI) the first line of treatment is to rapidly
      restore blood flow to the ischemic myocardium to limit infarct size. It is now
      well established that though clearly beneficial the positive outcomes of this
      intervention are limited by injury in response to the reperfusion itself in
      addition to the prior ischemia. This process is described as reperfusion injury
      and is considered to contribute to the arrhythmias, microvascular dysfunction and
      impaired cardiac contractility that is observed even after the restoration of
      coronary blood flow. Thus an important, currently unmet, therapeutic challenge is
      to address the outcomes of this reperfusion injury. In this article we review the
      evidence that flavonols and flavones may prove useful in preserving cardiac
      function after ischemia and reperfusion and consider the possible mechanisms, in
      particular the inhibition of kinases, by which they may exert protection.

PMID- 29589529
TI  - Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?
AB  - Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke
      widespread parasitic diseases with few treatment options and many of the
      clinically used drugs experiencing an extensive drug resistance phenomenon. In
      the last several years, the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) was
      cloned and characterized in the genome of these protozoa, with the aim to search
      for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P.
      falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the ?-CA
      class, L. donovani chagasi for a beta-CA (LdcCA), whereas T. cruzi genome
      contains an alpha-CA (TcCA). These three enzymes were characterized in detail and
      a number of in vitro potent and selective inhibitors belonging to the
      sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some
      of these inhibitors were also effective in cell cultures and animal models of
      protozoan infections, making them of considerable interest for the development of
      new antiprotozoan drugs with a novel mechanism of action.

PMID- 29589530
TI  - Virtual screening for development of new effective compounds against
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a notorious pathogenic bacterium causing a wide range of
      diseases from soft-tissue contamination, to more serious and deep-seated
      infections. This species is highlighted by its ability to express several kinds
      of virulence factors and to acquire genes related to drug resistance. Target this
      number of factors to design any drug is not an easy task. In this review we
      discuss the importance of computational methods to impulse the development of new
      drugs against S. aureus. The application of docking methods to screen large
      library of natural or synthetic compounds and to provide insights into action
      mechanisms is demonstrated. Particularly, highlighted the studies that validated
      in silico results with biochemical and microbiological assays. We also comment
      the computer-aided design of new molecules using some known inhibitors. The
      confirmation of in silico results with biochemical and microbiological assays
      allowed the identification of lead molecules that could be used for drug design
      such as rhodomyrtone, quinuclidine, berberine (and their derivative compounds).
      The fast development in the computational methods is essential to improve our
      ability to discovery new drugs, as well as to expand understanding about drug
      target interactions.

PMID- 29589531
TI  - A Focus on the Synthesis and Pharmacokinetics of Tocainide and its Analogues.
AB  - BACKGROUND Tocainide is an antiarrhythmic agent belonging to class IB that was
      primarily used for suppression of symptomatic ventricular arrhythmias. Tocainide
      was also reported to relieve pain such as tic douloureux, trigemina neuralgia in
      humans and tinnitus. Significant antinociception, as assayed on the hot-plate
      test, was observed after intraperitoneal injection of tocainide, too. By the mid
      1980s tocainide was emerging as a more consistently effective treatment for
      myotonic disorders. Numerous reports of serious adverse reactions led to the use
      of tocainide being discontinued, even though research on tocainide and its
      analogues, endowed with a better pharmacological profile, is still in progress
      for their potential usefulness in the treatment of myotonias. This review is
      focused on the description of the different synthetic routes to racemic and
      homochiral tocainide developed in the last decades, as well as analytical studies
      regarding enantioseparation methods. Finally, some analogues of tocainide
      reported in the literature, most of which with pharmacological studies, have been
      mentioned.

PMID- 29589532
TI  - Targeting Gap Junctions: New Insights in the Treatment of Major Depressive
      Disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is a multifactorial chronic and
      debilitating mood disease with high lifetime prevalence and associated with
      excess mortality. Treatments of this disease are not effective in all patients
      showing the need to find new therapeutic targets. OBJECTIVE: This review aims to
      update our knowledge about the involvement of astroglial gap junctions and
      hemichannels in MDD and to show how they have become potential targets for the
      treatment of this pathology. METHODS: The method applied in this review includes
      a systematic compilation of the relevant literature. RESULTS AND CONCLUSION: The
      use of rodent models of depression, gene analysis of hippocampal tissues of MDD
      patients and post-mortem studies of brains from MDD patients suggest that
      astrocytic gap junction dysfunction may be part of MDD etiologies. Chronic
      antidepressant treatments of rats, rat cultured cortical astrocytes and human
      astrocytoma cell lines support the hypothesis that the up-regulation of gap
      junctional coupling between astrocytes could be an underlying mechanism for the
      therapeutic effect of antidepressants. However, two recent functional studies
      suggest that connexin43 hemichannel activity is part of several antidepressants
      mode of action and that astrocyte gap junctional intercellular communication and
      hemichannels exert different effects on antidepressant drug response. Even if
      they emerge as new therapeutic targets for new and more active treatments,
      further studies are needed to decipher the sophisticated and respective role of
      astrocytic gap junctions and hemichannels in MDD.

PMID- 29589533
TI  - Liver and statins: a critical appraisal of the evidence.
AB  - Adverse drug reactions (ADRs) represent an important cause of morbidity and
      mortality worldwide. Statins are a class of drugs whose main adverse effects are
      drug-induced liver injury (DILI) and myopathy. Some of these may be predictable,
      due to their pharmacokinetic and pharmacodynamic properties, while others,
      unfortunately, are idiosyncratic. Genetic factors may also influence patient
      susceptibility to DILI and myopathy in the case of statins. This review will
      first discuss the role of statins in cardiovascular disease treatment and
      prevention and the underlying mechanisms of action. Furthermore, to explore the
      susceptibility of statin-induced adverse events such as myopathy and
      hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies
      (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion
      transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in
      the development of clinically relevant adverse events. Finally, we appraise the
      evidence for and against the use of statins in metabolic syndrome and in HCV
      infected patients, in terms of their safety and efficacy in cardiovascular
      events.

PMID- 29589534
TI  - The Role of Inflammation in Neurological Disorders.
AB  - Traditionally neurological diseases have been classified, on the basis of their
      pathogenesis, into vascular, degenerative, inflammatory and traumatic diseases.
      Examples of the main inflammatory neurological diseases include multiple
      sclerosis, which is characterized by an immune-mediated response against myelin
      proteins, and meningoencephalitis, where the inflammatory response is triggered
      by infectious agents. However, recent evidence suggests a potential role of
      inflammatory mechanisms also in neurological conditions not usually categorized
      as inflammatory, such as Alzheimer's disease, Parkinson's disease, Huntington'
      disease, amyotrophic lateral sclerosis, stroke and traumatic brain injuries. The
      activation of glial cells and of complement-mediated pathways, the synthesis of
      inflammation mediators, and the recruitment of leukocytes are the key elements of
      secondary inflammatory injury following a wide spectrum of primary brain
      injuries. A better understanding of the role that inflammatory processes play in
      the natural history of diseases is essential in order to identify potential
      therapeutic targets and to develop integrated pharmacological approaches acting
      at different levels and stages of the diseases.

PMID- 29589535
TI  - Signaling Pathways in Inflammation and Anti-inflammatory Therapies.
AB  - During the past decade, an abundance of new evidence highlighted the importance
      of inflammation in the development of chronic pathologies such as
      neurodegeneration, cancer, diabetes, cardiovascular disease and inflammatory
      bowel disease. However, most of the current therapies do not address the
      underlying problem and better therapies are urgently needed. A growing number of
      researchers have discovered various signaling pathways that are associated with
      the initiation and progression of inflammation. Among different pathways, we will
      focus on three classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and
      PI3K; and a non-classical inflammatory pathway, the Hippo. Recently, the Hippo
      pathway has been linked to various inflammatory modulators such as FoxO1/3,
      TNFalpha, IL-6, COX2, HIF-1alpha, AP-1, JAK and STAT. In this review, the
      molecular mechanisms, associated pathologies and selected drugs (both preclinical
      and clinical) of these signaling pathways will be summarized. Finally,
      limitations and potential risks of anti-inflammatory drugs will also be
      discussed.

PMID- 29589536
TI  - Cryptic Antimicrobial Peptides: Identification Methods and Current Knowledge of
      their Immunomodulatory Properties.
AB  - Cationic antimicrobial peptides (CAMPs), also known as host defence peptides
      (HDPs), are essential evolutionarily conserved components of innate immunity,
      constitutively or inducibly expressed in response to invasion by pathogens. In
      addition to a direct antimicrobial action, they are able to synergistically
      operate with other defence molecules to combat infection by neutralization of
      endotoxins, chemokine-like activities, induction of angiogenesis and wound
      repair. The importance of CAMPs has been highlighted in animal models and
      supported by observations in patient studies. CAMPs are attractive alternative
      candidates to antibiotic treatment, because they offer several advantages over
      the currently used drugs, moreover, knowledge on these peptides, especially
      regarding the intertwinement between their structure, function and mechanism of
      action, could be applied in the rational design of antimicrobial/anti
      inflammatory/wound healing enhancing drugs. CAMPs combat pathogens by targeting
      bacterial membranes and essential membrane-related functions, and, in some cases,
      also target intracellular components. Despite differences in their size and
      sequence, many of them share a net positive charge and fold into amphipathic
      structures after contact with bacterial surfaces or endotoxins like
      lipopolysaccharides and lipoteichoic acid. Due to their peculiar mechanism,
      acquisition of resistance towards these peptides would be difficult for the
      bacteria. Very interestingly it has been demonstrated that several proteins,
      including proteins apparently not involved in immunity, can behave as sources of
      CAMPs hidden in their primary structures and released by the action of host
      and/or bacterial proteases. The existence of these "cryptic CAMPs" suggests that
      the panel of antimicrobial peptides present in higher eukaryotes and the variety
      of functions they perform could be much wider and more complex than previously
      suspected. This review focuses on source, structure and mechanism of action of
      cryptic CAMPs, with special attention to their immunomodulatory functions.

PMID- 29589537
TI  - The Role of Host Defense Peptide Human beta-defensins in the Maintenance of Skin
      Barriers.
AB  - The epidermis functions as a first-line defense barrier that protects the body
      from the external environment. As a chemical hindrance, the epidermis possesses
      acidic pH, highly organized lipids and various host defense peptides, also known
      as antimicrobial peptides. Human beta-defensins (hBDs), one of the most important
      host defense peptide families found in our skin, are well-known for their broad
      spectrum microbicidal activities. However, there is a growing body of evidence
      indicating that hBDs also orchestrate several immunomodulatory functions and are
      the cornerstone that bridges the innate and adaptive immune responses during skin
      inflammation and infection. Moreover, recent work identified the potential role
      of hBDs in the regulation and maintenance of the skin barrier function. In this
      review, we describe the current knowledge concerning the role of hBDs in skin
      barriers and discuss the potential clinical implications of these peptides in
      cutaneous biology. Understanding the roles of hBDs in the regulation and
      maintenance of skin barriers may aid in the development of novel therapeutic
      strategies for skin conditions where the skin barrier is impaired, such as atopic
      dermatitis and psoriasis.

PMID- 29589538
TI  - Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or
      foes?
AB  - Tuberculosis is an ancient disease that has become a serious public health issue
      in recent years, although increasing incidence has been controlled, deaths caused
      by Mycobacterium tuberculosis have been accentuated due to the emerging of multi
      drug resistant strains and the comorbidity with diabetes mellitus and HIV. This
      situation is threatening the goals of World Health Organization (WHO) to
      eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as
      an alternative for the treatment of pulmonary tuberculosis, among the plausible
      molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides
      have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo
      in experimental models, nevertheless, these peptides not only have antimicrobial
      activity but also have a wide variety of functions such as angiogenesis, wound
      healing, immunomodulation and other well-described roles into the human
      physiology. Therapeutic strategies for tuberculosis using AMPs must be well
      thought prior to their clinical use; evaluating comorbidities, family history and
      risk factors to other diseases, since the wide function of AMPs, they could lead
      to collateral undesirable effects.

PMID- 29589539
TI  - Paneth Cells and their Antimicrobials in Intestinal Immunity.
AB  - Since the initial description of granular-rich small-intestinal crypt-based
      epithelial cells in 1872, today referred to as Paneth cells, a plethora of recent
      studies underlined their function in intestinal homeostasis. Paneth cells are
      evolutionary conserved highly secretory cells that produce antimicrobials to
      control gut microbial communities. Moreover, Paneth cells emerged as stem cell
      regulators that translate environmental cues into intestinal epithelial
      responses. Paneth cell disturbances may instigate intestinal inflammation and
      provide susceptibility to infection. Altered Paneth cell functions have been
      associated with a variety of inflammatory disease models and were linked to human
      intestinal disease processes including inflammatory bowel diseases such as
      Crohn's disease and ulcerative colitis. This review summarizes our current
      understanding of Paneth cells and their antimicrobials in health and disease.

PMID- 29589540
TI  - Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in
      Nonspecific Immunity Modulation.
AB  - Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of
      the innate immune defense system of mammals. Lf is present in colostrum, milk and
      mucosal sites, and it is also produced by polymorphonuclear neutrophils and
      secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named
      lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action
      in a wide array of pathogens. In addition, they display regulatory properties on
      components of nonspecific immunity, including toll-like receptors, proand anti
      inflammatory cytokines, and reactive oxygen species. Mechanisms explaining the
      ability of Lf and Lfcins to display both up- and down-modulatory properties on
      cells are not fully understood but result, in part, from their interactions with
      membrane receptors that elicit biochemical signal pathways, whereas other
      receptors enable the nuclear translocation of these molecules for the modulation
      of target genes. The dual role of Lf and Lfcins as antimicrobials and
      immunomodulators is of biotechnological and pharmaceutical interest. Native Lf
      and its peptide-derivatives from human and bovine sources, the recombinant
      versions of the human protein, and their synthetic peptides have potential
      application as adjunctive agents in therapies to combat infections caused by
      multi-resistant bacteria and those caused by fungi, protozoa and viruses, as well
      as in the prevention and reduction of several types of cancer and response to LPS
      shock, among other effects. In this review, we summarize the immunomodulatory
      properties of the unique multifunctional protein Lf and its N-terminus peptides.

PMID- 29589541
TI  - Antimicrobial Peptides in Human Disease: Therapeutic Approaches. Second of Two
      Parts.
AB  - Antimicrobial Peptides (AMPs) are produced by a variety of human immune and non
      immune cells in health and disease. In virtue of their antimicrobial activity,
      AMPs have been exploited in human disease and here this aspect will extensively
      be described. AMPs in comparison to antibiotics possess a larger spectrum of
      antimicrobial activity without inducing microbial resistance. Therefore, their
      use in the course of antibiotic-resistant infections is justified. AMP activity
      in early life, in the airways, in the oral and gastro-enteric system, in the skin
      and in the female reproductive tract, respectively, will be elucidated. In
      addition, the use of AMPs in sepsis will be discussed due to the frequency of
      this pathological condition characterized by multiple organ dysfunctions.
      Finally, the evidence that AMPs represent valid substitutes of antibiotics will
      be provided and a series of novel substances able to reinforce the innate immune
      response in different clinical settings will be discussed.

PMID- 29589542
TI  - Association Between Drug Burden Index and Functional and Cognitive Function in
      Patients with Multimorbidity
AB  - Background: Anticholinergic and sedative drugs are associated with adverse events
      such as cognitiveand functional impairment in elderly. The Drug Burden Index
      (DBI) is a measure of an individual's total exposure to anticholinergic and
      sedative drugs. Objetive: The study aimed to evaluate the association between the
      total DBI and cognitive and functional impairmentin patients with multimorbidity.
      Setting: Patients with multimorbidity enrolled in the IMPACTO project. Methods:
      Cross-sectional observational study. Main outcome measure: The anticholinergic
      and sedative exposure was calculated using DBI. The Pfeiffer Test(PT) was used
      for cognitive status and the Barthel Index (BI) for functional status. Results:
      336 patients were included (mean age 77.6 +/- 8.7 years, 54.2% men and a mean of
      11.5 +/- 3.7 prescribeddrugs). 180 patients (53.6%) exposed to anticholinergic
      and/or sedative drugs were identified. The median scoreobtained in PT was
      slightly higher in exposed patients (1 (IQR 0-2) and 2 (IQR 0-4), p = 0.082 in
      "non-exposed"and "exposed", respectively). The bivariate analysis showed an
      association [0.544 (95% CI 0.044-1.063, p =0.03)]. The median obtained in the BI
      analysis was 85.0 (IQR 30.0) and 75.5 (IQR 42.5) p = 0.002, in "nonexposed" and
      "exposed", respectively. After the adjusted analysis, a relationship was obtained
      between both the variables [-9,558 (95% CI-15,794; -3,321, p = 0.03)].
      Conclusion: Higher DBI is associated with the impairment of functional status
      and, slightly to the deteriorationof cognitive function in patients with
      multimorbidity. DBI should be considered in patients with multimorbidityto
      optimize the pharmacological treatment of a group of special interest due to its
      vulnerability.

PMID- 29589544
TI  - Tissue-specific Regulation of Innate Immune Responses by Human Cathelicidin LL
      37.
AB  - Cathelicidins form one of the major families of antimicrobial peptides and have
      been identified in many vertebrates, including humans. LL-37, the only human
      member of the cathelicidin family, is detected in most sites of the human body
      that is normally exposed to microbes, including the epithelial lining of the
      skin, gastrointestinal tract, genitourinary tract and lungs. This peptide is also
      expressed by a variety of epithelial cells and immune cells, such as neutrophils,
      monocytes and mast cells. LL-37 has emerged as a key component of innate immunity
      due to its direct antimicrobial activity against a broad spectrum of invading
      pathogens. It also exhibits diverse immunomodulatory functions by activating both
      pro- and anti-inflammatory mediators; inducing cell migration, proliferation and
      differentiation; and regulating apoptosis of epithelial cells and neutrophils.
      Given that the phenotypic and functional properties of immune compartments are
      different and significantly impacted by the anatomical sites, tissue-specific
      factors of host origin and microbial communities play important roles in the
      regulation of LL-37. This review summarizes the expression and biological
      functions of LL-37 and discusses its significant roles in the innate immune
      system based on its anatomical distribution.

PMID- 29589543
TI  - Phage-based Nanomedicines as New Immune Therapeutic Agents for Breast Cancer.
AB  - Despite years of investigation, breast cancer remains a major cause of death
      worldwide. Phage display is a powerful molecular method in which peptide and
      protein libraries can be displayed via genetic fusions on the surface of phages.
      This approach has tremendous potential for biomedical applications and has
      already facilitated the discovery of specific antibodies, specific antigens, and
      peptides with potential roles in the diagnosis and treatment of malignancies
      including breast cancer. In this review, we discuss the new and the latest
      advancements in the applications of the phage display technique in the provision
      of immune therapeutics for breast cancer.

PMID- 29589545
TI  - A Sweeping Role for MicroRNAs in Neuronal Disease, Vascular Disorders, and as
      Prognostic Indicators.

PMID- 29589546
TI  - A review on camptothecin analogs with promising cytotoxic profile.
AB  - Camptothecin (CPT), obtained from Camptotheca acuminata (Nyssaceae), is a
      quinoline type of alkaloid. Apart from various traditional uses, it is mainly
      used as a potential cytotoxic agent acting against a variety of cancer cell
      lines. Though researches have been continuing for last six decades, still it is a
      demanding task to design potent and cytotoxic CPTs. Different CPT analogs are
      synthesized to enhance the cytotoxic potential as well as to increase the
      pharmacokinetic properties of these analogs. Some of these analogs were proven to
      be clinically effective in different cancer cell lines. In this article,
      different CPT analogs have been highlighted extensively to get a detail insight
      about the structure-property relationships as well as different quantitative
      structure-activity relationships (QSARs) modeling of these analogs are also
      discussed. This study may be beneficial for designing newer CPT analogs in
      future.

PMID- 29589547
TI  - Implication of B23/nucleophosmin in Viral Infections, Potential Uses of B23/NPM1
      Inhibitors as Antiviral Therapy.
AB  - BACKGROUND: B23/nucleophosmin (B23/NPM1) is an abundant multifunctional protein
      mainly located in the nucleolus but constantly shuttling between the nucleus and
      cytosol. As a consequence of its constitutive expression, intracellular dynamics
      and binding capacities, B23/NPM1 interacts with multiple cellular factors in
      different cellular compartments, but also with viral proteins from both DNA and
      RNA viruses. B23/NPM1 influences overall viral replication of viruses like HIV,
      HBV, HCV, HDV and HPV by playing functional roles in different stages of viral
      replication including nuclear import, viral genome transcription and assembly, as
      well as final particle formation. Of note, some virus modify the subcellular
      localization, stability and/or increases B23/NPM1 expression levels on target
      cells, probably to foster B23/NPM1 functions in their own replicative cycle.
      RESULTS: This review summarizes current knowledge concerning the interaction of
      B23/NPM1 with several viral proteins during relevant human infections. The
      opportunities and challenges of targeting this well conserved host protein as a
      potentially new broad antiviral treatment are discussed in detail. Importantly,
      although initially conceived to treat cancer, a handful of B23/NPM1 inhibitors
      are currently available to test on viral infection models. CONCLUSIONS: As
      B23/NPM1 partakes in key steps of viral replication and some viral infections
      remains as unsolved medical needs, an appealing idea may be the expedite
      evaluation of B23/NPM1 inhibitors in viral infections. Furthermore, worth to be
      address is if the up regulation of B23/NPM1 protein levels that follows
      persistent viral infections may be instrumental to the malignant transformation
      induced by virus like HBV and HCV.

PMID- 29589548
TI  - Characterization of Regulatory T-Cells in Multiple Sclerosis Patients Treated
      with Interferon Beta-1a.
AB  - BACKGROUND: Regulatory T-Cells (Treg Cells), as one of the immune system
      components, have been highly effective in the autoimmune diseases prevention,
      particularly multiple sclerosis (MS). Cytokine-based therapies such as interferon
      beta-1a (IFN-beta1a) is a common drug in MS treatment; however, its exact
      mechanisms are insufficiently described. OBJECTIVE: Therefore, the goal of this
      study was to evaluate the in vivo impact of IFN-beta1a on the Treg Cells in MS.
      METHODS: In this case-control study, Treg Cells were analysed by flowcytometry in
      IFN-beta1a-treated relapsing-remitting MS (RRMS) in comparison with new cases of
      MS and healthy subjects. RESULTS: The frequency of Treg Cells in the IFN-beta1a
      treated-RRMS was increased compared to the new MS cases (P < 0.05). Furthermore,
      the MFIs of the CD4 and CD25 in T-Cells were significantly reduced in new cases
      of MS and IFN-beta1a-treated RRMS than the control subjects (P < 0.05).
      Additionally, the FoxP3 MFIs in CD4 + CD25 + T-Cells of IFN-beta1a-treated RRMS
      were significantly lower than the new cases of MS. CONCLUSION: Overall, the
      present study indicated that IFN-beta1a as an immunomodulatory drug led to an
      enhancement in Treg Cells population without CD4, CD25, and FoxP3 molecules
      upregulation in Treg Cells.

PMID- 29589549
TI  - Effect of Laparoscopic Sleeve Gastrectomy on Thyroid Hormones in Euthyroid Obese
      Patients.
AB  - INTRODUCTION: In obese patients, the incidences of several thyroid disorders have
      increased in comparison to the general population. This study is aimed to
      investigate the effect of laparoscopic sleeve gastrectomy (LSG) on thyroid
      function tests in obese patients. METHODS: The patient files of 186 individuals
      who underwent laparoscopic sleeve gastrectomy surgery were examined
      retrospectively. Forty-nine females and 29 males comprising a total of 78
      patients were included in the study. The routine physical examination findings
      and laboratory parameters recorded preoperatively were compared with their
      counterparts obtained in the postoperative sixth month. RESULTS: The mean
      preoperative body mass index (BMI) levels of the patients in the study was
      calculated as 46.91 kg/m2, whereas the mean BMI in the postoperative sixth month
      was 30.35 kg/m2 (p<0.001). Prior to the sleeve gastrectomy, the mean thyroid
      stimulating hormone (TSH) level of the patients was 2.53 +/-2.06 uIU/mL; however,
      a significant reduction was observed in the mean TSH level during the
      postoperative sixth month, which was calculated as 1.77 +/-1.12 uIU/mL (p=0.015).
      The mean free T4 level was 1.18+/-0.1 ng/dL in the preoperative period, but this
      increased to 1.22 +/-0.24 ng/dL postoperatively, an insignificant change. The
      decrease in the TSH levels after the LSG was determined not to be correlated with
      the decrease in body weight. CONCLUSION: The results of our study demonstrate
      that the levels of TSH decreased significantly in patients who underwent LSG and
      that the decrease was independent of the changes in BMI.

PMID- 29589550
TI  - The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice.
AB  - BACKGROUND: Previous studies have demonstrated that flagellin, a component of
      bacterial flagella, engages Toll-Like receptor 5 (TLR-5) causing the activation
      of the Myeloid Differentiation Factor-88 (MYD-88) pathway that leads to the
      production of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha
      (TNF-alpha) and Interleukin-12 (IL-12). In physiological levels, cytokines can
      aid in protection against infectious agents. However, excessive production of
      cytokines can lead to septic shock during sepsis. OBJECTIVE: In this study, we
      aimed at investigating the effect of denatured flagellin on hindering the effects
      induced by intact flagellin or flagellated Pseudomonas aeruginosa on the Toll
      Like Receptor-5 (TLR-5) in mice. METHODS: Mouse mononuclear cells (MNCs) were
      cultured with intact flagellin, heat-denatured flagellin, TLR-5 antagonist,
      Pseudomonas aeruginosa, and TLR-4 antagonist each alone or in combinations.
      Supernatants were collected at 4 hours post incubation to assess the levels of IL
      12 and TNF-alpha by Enzyme-Linked ImmunoAssay (ELISA). Furthermore, groups of
      BALB/c mice were injected intraperitoneally (IP) with Pseudomonas aeruginosa, LPS
      RS, intact flagellin, and denatured flagellin, each alone or in different
      combinations. Serum levels of IL-12 and TNF-alpha were measured at 2, 4, and 6
      hours post injections of Pseudomonas aeruginosa or intact flagellin. RESULTS:
      Pretreatment with denatured flagellin significantly reduced the amount of TNF
      alpha and IL-12 produced both in vitro and in vivo by intact flagellin or
      Pseudomonas aeruginosa. CONCLUSION: Denatured flagellin suppressed the production
      of the pro-inflammatory cytokines induced by intact flagellin or Pseudomonas
      aeruginosa both in vitro and in vivo, probably by blocking TLR5. Denatured
      flagellin might be considered as an anti-septic shock agent.

PMID- 29589551
TI  - Recent Patents on Polymeric Nanoparticles for Cancer Therapy.
AB  - BACKGROUND: Cancer is a major problem which has claimed so many lives throughout
      the world. Although a number of resources have been utilized for the development
      of cancer therapeutics, no effective cure has been found so far. OBJECTIVE:
      Therefore, the need for looking at evolving technologies has become very
      important to get a solution to this problem. Among these, nanotechnology has got
      so much popularity and became feasible in the past few years. Nanotechnology is
      presently used as the most preferable drug delivery platform for cancer therapy.
      METHOD: A variety of nanomaterials based on lipid, polymer, metal or magnet have
      been developed for enhancement of the efficiency of current treatment. RESULTS:
      Recently, polymeric-nanoparticles have been exploited as a carrier of many drug
      substances for invasive and non-invasive routes of delivery. CONCLUSION: In this
      manuscript, the authors have reviewed different aspects of nanoparticles, recent
      patents and research issues related to cancer.

PMID- 29589552
TI  - Evaluation and Management of Children with Thyrotoxicosis.
AB  - BACKGROUND: Uncontrolled thyrotoxicosis, especially in early infancy, may cause
      irreversible damage to the central nervous system as well as profound effects on
      the function of many organs. Thyrotoxicosis has multiple etiologies and treatment
      depends on the underlying etiology. An accurate diagnosis is essential so that
      appropriate treatment can be initiated without undue delay. OBJECTIVE: To review
      in depth the evaluation, diagnosis, and treatment of children with
      thyrotoxicosis. METHODS: A PubMed search was completed in Clinical Queries using
      the key terms "thyrotoxicosis" and "hyperthyroidism". The search strategy
      included meta-analysis, randomized controlled trials, clinical trials,
      observational studies, and reviews. Patents were searched using the key terms
      "thyrotoxicosis" and "hyperthyroidism" from www.freepatentsonline.com and
      www.google.com/patents. RESULTS: Graves' disease accounts for approximately 96%
      of pediatric cases of thyrotoxicosis. Other causes include Hashitoxicosis, toxic
      adenoma, toxic multinodular goiter, subacute granulomatous thyroiditis, acute
      suppurative thyroiditis, pituitary thyroid-stimulating hormone-secreting adenoma,
      pituitary thyroid hormone resistance, iodine-induced thyrotoxicosis, and drug
      induced thyrotoxicosis. Familiarity of the clinical features would allow prompt
      diagnosis and institution of treatment. The underlying cause of thyrotoxicosis
      should be treated if possible. Treatment options for Graves' disease include
      antithyroid medications, radioiodine therapy, and surgery. Recent patents related
      to the management of thyrotoxicosis are discussed. CONCLUSION: Currently,
      antithyroid medications are considered to be the initial treatment of choice for
      Graves' disease in the pediatric age group. Radioactive iodine treatment is
      generally used for children with poor compliance with antithyroid medications,
      children not in remission after 1 to 2 years of antithyroid medications, and
      children with a major adverse effect while receiving an antithyroid medication.
      Total or near-total thyroidectomy should be considered in children younger than 5
      years of age who do not respond to or experience a major adverse effect to
      antithyroid medications. Surgery should also be considered in those with very
      large goiter, severe ophthalmopathy, pregnancy, persistent hyperthyroidism in
      spite of treatment with antithyroid medications and radioactive iodine, and
      personal preference.

PMID- 29589553
TI  - Young Children Talking about Food and Health.
AB  - BACKGROUND: Limited patents have explored young children's understanding of the
      connection between food and health. This qualitative study aimed to narrow this
      gap by investigating young children's health conceptions. METHODS: Seventy-two
      children, 5 to 7 years of age, participated in this study. Two instruments, the
      demographic survey and child interview survey, were used to collect data. Data
      were analyzed following the processes of conducting initial coding, specifying
      categories, and combining categories to develop themes. RESULTS: Children in this
      age group had certain knowledge about five food categories: Diary, meat, grain,
      fruit, and vegetables. They believed that food from these five categories were
      good for them and would make them strong; they also believed that sweets and
      salty foods were unhealthy, yet many of them preferred sweets and listed them as
      top snack choices. These children demonstrated awareness of complex nutritional
      terms such as vitamins, fiber, and protein yet misconceptions became evident when
      were asked to identify overall health effects of mixed dishes for which various
      components were not easily recognizable. CONCLUSION: This study provides new
      insights into children's understanding about food, nutrition, and health that can
      impact future education endeavors. Findings from this study can be helpful to
      inform educators about the development of nutritional education curricula
      specifically targeting nutritional values regarding foods being processed in
      different ways.

PMID- 29589554
TI  - Sparse Tensor Decomposition for Haplotype Assembly of Diploids and Polyploids.
AB  - BACKGROUND: Haplotype assembly is the task of reconstructing haplotypes of an
      individual from a mixture of sequenced chromosome fragments. Haplotype
      information enables studies of the effects of genetic variations on an organism's
      phenotype. Most of the mathematical formulations of haplotype assembly are known
      to be NP-hard and haplotype assembly becomes even more challenging as the
      sequencing technology advances and the length of the paired-end reads and inserts
      increases. Assembly of haplotypes polyploid organisms is considerably more
      difficult than in the case of diploids. Hence, scalable and accurate schemes with
      provable performance are desired for haplotype assembly of both diploid and
      polyploid organisms. RESULTS: We propose a framework that formulates haplotype
      assembly from sequencing data as a sparse tensor decomposition. We cast the
      problem as that of decomposing a tensor having special structural constraints and
      missing a large fraction of its entries into a product of two factors, U and
      [Formula: see text]; tensor [Formula: see text] reveals haplotype information
      while U is a sparse matrix encoding the origin of erroneous sequencing reads. An
      algorithm, AltHap, which reconstructs haplotypes of either diploid or polyploid
      organisms by iteratively solving this decomposition problem is proposed. The
      performance and convergence properties of AltHap are theoretically analyzed and,
      in doing so, guarantees on the achievable minimum error correction scores and
      correct phasing rate are established. The developed framework is applicable to
      diploid, biallelic and polyallelic polyploid species. The code for AltHap is
      freely available from https://github.com/realabolfazl/AltHap . CONCLUSION: AltHap
      was tested in a number of different scenarios and was shown to compare favorably
      to state-of-the-art methods in applications to haplotype assembly of diploids,
      and significantly outperforms existing techniques when applied to haplotype
      assembly of polyploids.

PMID- 29589555
TI  - Bayesian graphical models for computational network biology.
AB  - BACKGROUND: Computational network biology is an emerging interdisciplinary
      research area. Among many other network approaches, probabilistic graphical
      models provide a comprehensive probabilistic characterization of interaction
      patterns between molecules and the associated uncertainties. RESULTS: In this
      article, we first review graphical models, including directed, undirected, and
      reciprocal graphs (RG), with an emphasis on the RG models that are curiously
      under-utilized in biostatistics and bioinformatics literature. RG's strictly
      contain chain graphs as a special case and are suitable to model reciprocal
      causality such as feedback mechanism in molecular networks. We then extend the RG
      approach to modeling molecular networks by integrating DNA-, RNA- and protein
      level data. We apply the extended RG method to The Cancer Genome Atlas multi
      platform ovarian cancer data and reveal several interesting findings.
      CONCLUSIONS: This study aims to review the basics of different probabilistic
      graphical models as well as recent development in RG approaches for network
      modeling. The extension presented in this paper provides a principled and
      efficient way of integrating DNA copy number, DNA methylation, mRNA gene
      expression and protein expression.

PMID- 29589556
TI  - A Bayesian approach to determine the composition of heterogeneous cancer tissue.
AB  - BACKGROUND: Cancer Tissue Heterogeneity is an important consideration in cancer
      research as it can give insights into the causes and progression of cancer. It is
      known to play a significant role in cancer cell survival, growth and metastasis.
      Determining the compositional breakup of a heterogeneous cancer tissue can also
      help address the therapeutic challenges posed by heterogeneity. This necessitates
      a low cost, scalable algorithm to address the challenge of accurate estimation of
      the composition of a heterogeneous cancer tissue. METHODS: In this paper, we
      propose an algorithm to tackle this problem by utilizing the data of accurate,
      but high cost, single cell line cell-by-cell observation methods in low cost
      aggregate observation method for heterogeneous cancer cell mixtures to obtain
      their composition in a Bayesian framework. RESULTS: The algorithm is analyzed and
      validated using synthetic data and experimental data. The experimental data is
      obtained from mixtures of three separate human cancer cell lines, HCT116
      (Colorectal carcinoma), A2058 (Melanoma) and SW480 (Colorectal carcinoma).
      CONCLUSION: The algorithm provides a low cost framework to determine the
      composition of heterogeneous cancer tissue which is a crucial aspect in cancer
      research.

PMID- 29589557
TI  - Selected research articles from the 2017 International Workshop on Computational
      Network Biology: Modeling, Analysis, and Control (CNB-MAC).

PMID- 29589558
TI  - Heuristic algorithms for feature selection under Bayesian models with block
      diagonal covariance structure.
AB  - BACKGROUND: Many bioinformatics studies aim to identify markers, or features,
      that can be used to discriminate between distinct groups. In problems where
      strong individual markers are not available, or where interactions between gene
      products are of primary interest, it may be necessary to consider combinations of
      features as a marker family. To this end, recent work proposes a hierarchical
      Bayesian framework for feature selection that places a prior on the set of
      features we wish to select and on the label-conditioned feature distribution.
      While an analytical posterior under Gaussian models with block covariance
      structures is available, the optimal feature selection algorithm for this model
      remains intractable since it requires evaluating the posterior over the space of
      all possible covariance block structures and feature-block assignments. To
      address this computational barrier, in prior work we proposed a simple suboptimal
      algorithm, 2MNC-Robust, with robust performance across the space of block
      structures. Here, we present three new heuristic feature selection algorithms.
      RESULTS: The proposed algorithms outperform 2MNC-Robust and many other popular
      feature selection algorithms on synthetic data. In addition, enrichment analysis
      on real breast cancer, colon cancer, and Leukemia data indicates they also output
      many of the genes and pathways linked to the cancers under study. CONCLUSIONS:
      Bayesian feature selection is a promising framework for small-sample high
      dimensional data, in particular biomarker discovery applications. When applied to
      cancer data these algorithms outputted many genes already shown to be involved in
      cancer as well as potentially new biomarkers. Furthermore, one of the proposed
      algorithms, SPM, outputs blocks of heavily correlated genes, particularly useful
      for studying gene interactions and gene networks.

PMID- 29589559
TI  - Investigation of model stacking for drug sensitivity prediction.
AB  - BACKGROUND: A significant problem in precision medicine is the prediction of drug
      sensitivity for individual cancer cell lines. Predictive models such as Random
      Forests have shown promising performance while predicting from individual genomic
      features such as gene expressions. However, accessibility of various other forms
      of data types including information on multiple tested drugs necessitates the
      examination of designing predictive models incorporating the various data types.
      RESULTS: We explore the predictive performance of model stacking and the effect
      of stacking on the predictive bias and squared error. In addition we discuss the
      analytical underpinnings supporting the advantages of stacking in reducing
      squared error and inherent bias of random forests in prediction of outliers. The
      framework is tested on a setup including gene expression, drug target, physical
      properties and drug response information for a set of drugs and cell lines.
      CONCLUSION: The performance of individual and stacked models are compared. We
      note that stacking models built on two heterogeneous datasets provide superior
      performance to stacking different models built on the same dataset. It is also
      noted that stacking provides a noticeable reduction in the bias of our predictors
      when the dominant eigenvalue of the principle axis of variation in the residuals
      is significantly higher than the remaining eigenvalues.

PMID- 29589560
TI  - Simulating variance heterogeneity in quantitative genome wide association
      studies.
AB  - BACKGROUND: Analyzing Variance heterogeneity in genome wide association studies
      (vGWAS) is an emerging approach for detecting genetic loci involved in gene-gene
      and gene-environment interactions. vGWAS analysis detects variability in
      phenotype values across genotypes, as opposed to typical GWAS analysis, which
      detects variations in the mean phenotype value. RESULTS: A handful of vGWAS
      analysis methods have been recently introduced in the literature. However, very
      little work has been done for evaluating these methods. To enable the development
      of better vGWAS analysis methods, this work presents the first quantitative vGWAS
      simulation procedure. To that end, we describe the mathematical framework and
      algorithm for generating quantitative vGWAS phenotype data from genotype
      profiles. Our simulation model accounts for both haploid and diploid genotypes
      under different modes of dominance. Our model is also able to simulate any number
      of genetic loci causing mean and variance heterogeneity. CONCLUSIONS: We
      demonstrate the utility of our simulation procedure through generating a variety
      of genetic loci types to evaluate common GWAS and vGWAS analysis methods. The
      results of this evaluation highlight the challenges current tools face in
      detecting GWAS and vGWAS loci.

PMID- 29589561
TI  - Feature selection with interactions in logistic regression models using
      multivariate synergies for a GWAS application.
AB  - BACKGROUND: Genotype-phenotype association has been one of the long-standing
      problems in bioinformatics. Identifying both the marginal and epistatic effects
      among genetic markers, such as Single Nucleotide Polymorphisms (SNPs), has been
      extensively integrated in Genome-Wide Association Studies (GWAS) to help derive
      "causal" genetic risk factors and their interactions, which play critical roles
      in life and disease systems. Identifying "synergistic" interactions with respect
      to the outcome of interest can help accurate phenotypic prediction and understand
      the underlying mechanism of system behavior. Many statistical measures for
      estimating synergistic interactions have been proposed in the literature for such
      a purpose. However, except for empirical performance, there is still no
      theoretical analysis on the power and limitation of these synergistic interaction
      measures. RESULTS: In this paper, it is shown that the existing information
      theoretic multivariate synergy depends on a small subset of the interaction
      parameters in the model, sometimes on only one interaction parameter. In
      addition, an adjusted version of multivariate synergy is proposed as a new
      measure to estimate the interactive effects, with experiments conducted over both
      simulated data sets and a real-world GWAS data set to show the effectiveness.
      CONCLUSIONS: We provide rigorous theoretical analysis and empirical evidence on
      why the information-theoretic multivariate synergy helps with identifying genetic
      risk factors via synergistic interactions. We further establish the rigorous
      sample complexity analysis on detecting interactive effects, confirmed by both
      simulated and real-world data sets.

PMID- 29589562
TI  - Qcorp: an annotated classification corpus of Chinese health questions.
AB  - BACKGROUND: Health question-answering (QA) systems have become a typical
      application scenario of Artificial Intelligent (AI). An annotated question corpus
      is prerequisite for training machines to understand health information needs of
      users. Thus, we aimed to develop an annotated classification corpus of Chinese
      health questions (Qcorp) and make it openly accessible. METHODS: We developed a
      two-layered classification schema and corresponding annotation rules on basis of
      our previous work. Using the schema, we annotated 5000 questions that were
      randomly selected from 5 Chinese health websites within 6 broad sections. 8
      annotators participated in the annotation task, and the inter-annotator agreement
      was evaluated to ensure the corpus quality. Furthermore, the distribution and
      relationship of the annotated tags were measured by descriptive statistics and
      social network map. RESULTS: The questions were annotated using 7101 tags that
      covers 29 topic categories in the two-layered schema. In our released corpus, the
      distribution of questions on the top-layered categories was treatment of 64.22%,
      diagnosis of 37.14%, epidemiology of 14.96%, healthy lifestyle of 10.38%, and
      health provider choice of 4.54% respectively. Both the annotated health questions
      and annotation schema were openly accessible on the Qcorp website. Users can
      download the annotated Chinese questions in CSV, XML, and HTML format.
      CONCLUSIONS: We developed a Chinese health question corpus including 5000
      manually annotated questions. It is openly accessible and would contribute to the
      intelligent health QA system development.

PMID- 29589563
TI  - A pattern learning-based method for temporal expression extraction and
      normalization from multi-lingual heterogeneous clinical texts.
AB  - BACKGROUND: Temporal expression extraction and normalization is a fundamental and
      essential step in clinical text processing and analyzing. Though a variety of
      commonly used NLP tools are available for medical temporal information
      extraction, few work is satisfactory for multi-lingual heterogeneous clinical
      texts. METHODS: A novel method called TEER is proposed for both multi-lingual
      temporal expression extraction and normalization from various types of narrative
      clinical texts including clinical data requests, clinical notes, and clinical
      trial summaries. TEER is characterized as temporal feature summarization,
      heuristic rule generation, and automatic pattern learning. By representing a
      temporal expression as a triple <M, A, N>, TEER identifies temporal mentions M,
      assigns type attributes A to M, and normalizes the values of M into formal
      representations N. RESULTS: Based on two heterogeneous clinical text datasets:
      400 actual clinical requests in English and 1459 clinical discharge summaries in
      Chinese. TEER was compared with six state-of-the-art baselines. The results
      showed that TEER achieved a precision of 0.948 and a recall of 0.877 on the
      English clinical requests, while a precision of 0.941 and a recall of 0.932 on
      the Chinese discharge summaries. CONCLUSIONS: An automated method TEER for multi
      lingual temporal expression extraction was presented. Based on the two datasets
      containing heterogeneous clinical texts, the comparison results demonstrated the
      effectiveness of the TEER method in multi-lingual temporal expression extraction
      from heterogeneous narrative clinical texts.

PMID- 29589564
TI  - Intrinsically Bayesian robust classifier for single-cell gene expression
      trajectories in gene regulatory networks.
AB  - BACKGROUND: Expression-based phenotype classification using either microarray or
      RNA-Seq measurements suffers from a lack of specificity because pathway timing is
      not revealed and expressions are averaged across groups of cells. This paper
      studies expression-based classification under the assumption that single-cell
      measurements are sampled at a sufficient rate to detect regulatory timing. Thus,
      observations are expression trajectories. In effect, classification is performed
      on data generated by an underlying gene regulatory network. RESULTS: Network
      regulation is modeled via a Boolean network with perturbation, regulation not
      fully determined owing to inherent biological randomness. The binary assumption
      is not critical because the resulting Markov chain characterizes expression
      trajectories. We assume a partially known Gaussian observation model belonging to
      an uncertainty class of models. We derive the intrinsically Bayesian robust
      classifier to discriminate between wild-type and mutated networks based on
      expression trajectories. The classifier minimizes the expected error across the
      uncertainty class relative to the prior distribution. We test it using a
      mammalian cell-cycle model, discriminating between the normal network and one in
      which gene p27 is mutated, thereby producing a cancerous phenotype. Tests examine
      all model aspects, including trajectory length, perturbation probability, and the
      hyperparameters governing the prior distribution over the uncertainty class.
      CONCLUSIONS: Simulations show the rates at which the expected error is diminished
      by smaller perturbation probability, longer trajectories, and hyperparameters
      that tighten the prior distribution relative to the unknown true network. For
      average-expression measurement, methods have been proposed to obtain prior
      distributions. These should be extended to the more mathematically difficult, but
      more informative, expression trajectories.

PMID- 29589565
TI  - Detangling PPI networks to uncover functionally meaningful clusters.
AB  - BACKGROUND: Decomposing a protein-protein interaction network (PPI network) into
      non-overlapping clusters or communities, sometimes called "network modules," is
      an important way to explore functional roles of sets of genes. When the method to
      accomplish this decomposition is solely based on purely graph-theoretic measures
      of the interconnection structure of the network, this is often called
      unsupervised clustering or community detection. In this study, we compare
      unsupervised computational methods for decomposing a PPI network into non
      overlapping modules. A method is preferred if it results in a large proportion of
      nodes being assigned to functionally meaningful modules, as measured by
      functional enrichment over terms from the Gene Ontology (GO). RESULTS: We compare
      the performance of three popular community detection algorithms with the same
      algorithms run after the network is pre-processed by removing and reweighting
      based on the diffusion state distance (DSD) between pairs of nodes in the
      network. We call this "detangling" the network. In almost all cases, we find that
      detangling the network based on the DSD distance reweighting provides more
      meaningful clusters. CONCLUSIONS: Re-embedding using the DSD distance metric,
      before applying standard community detection algorithms, can assist in uncovering
      GO functionally enriched clusters in the yeast PPI network.

PMID- 29589566
TI  - Constraints on signaling network logic reveal functional subgraphs on Multiple
      Myeloma OMIC data.
AB  - BACKGROUND: The integration of gene expression profiles (GEPs) and large-scale
      biological networks derived from pathways databases is a subject which is being
      widely explored. Existing methods are based on network distance measures among
      significantly measured species. Only a small number of them include the
      directionality and underlying logic existing in biological networks. In this
      study we approach the GEP-networks integration problem by considering the network
      logic, however our approach does not require a prior species selection according
      to their gene expression level. RESULTS: We start by modeling the biological
      network representing its underlying logic using Logic Programming. This model
      points to reachable network discrete states that maximize a notion of harmony
      between the molecular species active or inactive possible states and the
      directionality of the pathways reactions according to their activator or
      inhibitor control role. Only then, we confront these network states with the GEP.
      From this confrontation independent graph components are derived, each of them
      related to a fixed and optimal assignment of active or inactive states. These
      components allow us to decompose a large-scale network into subgraphs and their
      molecular species state assignments have different degrees of similarity when
      compared to the same GEP. We apply our method to study the set of possible states
      derived from a subgraph from the NCI-PID Pathway Interaction Database. This graph
      links Multiple Myeloma (MM) genes to known receptors for this blood cancer.
      CONCLUSION: We discover that the NCI-PID MM graph had 15 independent components,
      and when confronted to 611 MM GEPs, we find 1 component as being more specific to
      represent the difference between cancer and healthy profiles.

PMID- 29589567
TI  - Causal risk factor discovery for severe acute kidney injury using electronic
      health records.
AB  - BACKGROUND: Acute kidney injury (AKI), characterized by abrupt deterioration of
      renal function, is a common clinical event among hospitalized patients and it is
      associated with high morbidity and mortality. AKI is defined in three stages with
      stage-3 being the most severe phase which is irreversible. It is important to
      effectively discover the true risk factors in order to identify high-risk AKI
      patients and allow better targeting of tailored interventions. However, Stage-3
      AKI patients are very rare (only 0.2% of AKI patients) with a large scale of
      features available in EHR (1917 potential risk features), yielding a scenario
      unfeasible for any correlation-based feature selection or modeling method. This
      study aims to discover the key factors and improve the detection of Stage-3 AKI.
      METHODS: A causal discovery method (McDSL) is adopted for causal discovery to
      infer true causal relationship between information buried in EHR (such as
      medication, diagnosis, laboratory tests, comorbidities and etc.) and Stage-3 AKI
      risk. The research approach comprised two major phases: data collection, and
      causal discovery. The first phase is propose to collect the data from HER
      (includes 358 encounters and 891 risk factors). Finally, McDSL is employed to
      discover the causal risk factors of Stage-3 AKI, and five well-known machine
      learning models are built for predicting Stage-3 AKI with 10-fold cross
      validation (predictive accuracy were measured by AUC, precision, recall and F
      score). RESULTS: McDSL is useful for further research of EHR. It is able to
      discover four causal features, all selected features are medications that are
      modifiable. The latest research of machine learning is employed to compare the
      performance of prediction, and the experimental result has verified the selected
      features are pivotal. CONCLUSIONS: The features selected by McDSL, which enable
      us to achieve significant dimension reduction without sacrificing prediction
      accuracy, suggesting potential clinical use such as helping physicians develop
      better prevention and treatment strategies.

PMID- 29589568
TI  - Heterogeneous network propagation for herb target identification.
AB  - BACKGROUND: Identifying targets of herbs is a primary step for investigating
      pharmacological mechanisms of herbal drugs in Traditional Chinese medicine (TCM).
      Experimental targets identification of herbs is a difficult and time-consuming
      work. Computational method for identifying herb targets is an efficient approach.
      However, how to make full use of heterogeneous network data about herbs and
      targets to improve the performance of herb targets prediction is still a dilemma.
      METHODS: In our study, a random walk algorithm on the heterogeneous herb-target
      network (named heNetRW) has been proposed to identify protein targets of herbs.
      By building a heterogeneous herb-target network involving herbs, targets and
      their interactions and simulating random walk algorithm on the network, the
      candidate targets of the given herb can be predicted. RESULTS: The experimental
      results on large-scale dataset showed that heNetRW had higher performance of
      targets prediction than PRINCE (improved F1-score by 0.08 and Hit@1 by 21.34% in
      one validation setting, and improved F1-score by 0.54 and Hit@1 by 69.08% in the
      other validation setting). Furthermore, we evaluated novel candidate targets of
      two herbs (rhizoma coptidis and turmeric), which showed our approach could
      generate potential targets that are valuable for further experimental
      investigations. CONCLUSIONS: Compared with PRINCE algorithm, heNetRW algorithm
      can fuse more known information (such as, known herb-target associations and
      pathway-based similarities of protein pairs) to improve prediction performance.
      Experimental results also indicated heNetRW had higher performance than PRINCE.
      The prediction results not only can be used to guide the selection of candidate
      targets of herbs, but also help to reveal the molecule mechanisms of herbal
      drugs.

PMID- 29589569
TI  - A bibliometric analysis of natural language processing in medical research.
AB  - BACKGROUND: Natural language processing (NLP) has become an increasingly
      significant role in advancing medicine. Rich research achievements of NLP methods
      and applications for medical information processing are available. It is of great
      significance to conduct a deep analysis to understand the recent development of
      NLP-empowered medical research field. However, limited study examining the
      research status of this field could be found. Therefore, this study aims to
      quantitatively assess the academic output of NLP in medical research field.
      METHODS: We conducted a bibliometric analysis on NLP-empowered medical research
      publications retrieved from PubMed in the period 2007-2016. The analysis focused
      on three aspects. Firstly, the literature distribution characteristics were
      obtained with a statistics analysis method. Secondly, a network analysis method
      was used to reveal scientific collaboration relations. Finally, thematic
      discovery and evolution was reflected using an affinity propagation clustering
      method. RESULTS: There were 1405 NLP-empowered medical research publications
      published during the 10 years with an average annual growth rate of 18.39%. 10
      most productive publication sources together contributed more than 50% of the
      total publications. The USA had the highest number of publications. A moderately
      significant correlation between country's publications and GDP per capita was
      revealed. Denny, Joshua C was the most productive author. Mayo Clinic was the
      most productive affiliation. The annual co-affiliation and co-country rates
      reached 64.04% and 15.79% in 2016, respectively. 10 main great thematic areas
      were identified including Computational biology, Terminology mining, Information
      extraction, Text classification, Social medium as data source, Information
      retrieval, etc. CONCLUSIONS: A bibliometric analysis of NLP-empowered medical
      research publications for uncovering the recent research status is presented. The
      results can assist relevant researchers, especially newcomers in understanding
      the research development systematically, seeking scientific cooperation partners,
      optimizing research topic choices and monitoring new scientific or technological
      activities.

PMID- 29589570
TI  - Proceedings of the Fourth Biennial Conference of the Society for Implementation
      Research Collaboration (SIRC) 2017: implementation mechanisms: what makes
      implementation work and why? part 1.

PMID- 29589571
TI  - Leveraging text skeleton for de-identification of electronic medical records.
AB  - BACKGROUND: De-identification is the first step to use these records for data
      processing or further medical investigations in electronic medical records.
      Consequently, a reliable automated de-identification system would be of high
      value. METHODS: In this paper, a method of combining text skeleton and recurrent
      neural network is proposed to solve the problem of de-identification. Text
      skeleton is the general structure of a medical record, which can help neural
      networks to learn better. RESULTS: We evaluated our method on three datasets
      involving two English datasets from i2b2 de-identification challenge and a
      Chinese dataset we annotated. Empirical results show that the text skeleton based
      method we proposed can help the network to recognize protected health
      information. CONCLUSIONS: The comparison between our method and state-of-the-art
      frameworks indicates that our method achieves high performance on the problem of
      medical record de-identification.

PMID- 29589572
TI  - An openEHR based approach to improve the semantic interoperability of clinical
      data registry.
AB  - BACKGROUND: Clinical data registry is designed to collect and manage information
      about the practices and outcomes of a patient population for improving the
      quality and safety of care and facilitating novel researches. Semantic
      interoperability is a challenge when integrating the data from more than one
      clinical data registry. The openEHR approach can represent the information and
      knowledge semantics by multi-level modeling, and it advocates the use of
      collaborative modeling to facilitate reusing existing archetypes with consistent
      semantics so as to be a potential solution to improve the semantic
      interoperability. METHODS: This paper proposed an openEHR based approach to
      improve the semantic interoperability of clinical data registry. The approach
      consists of five steps: clinical data registry meta-information collection, data
      element definition, archetype modeling, template editing, and implementation.
      Through collaborative modeling and maximum reusing of existing archetype at the
      archetype modeling step, the approach can improve semantic interoperability. To
      verify the feasibility of the approach, this paper conducted a case study of
      building a Coronary Computed Tomography Angiography (CCTA) registry that can
      interoperate with an existing Electronic Health Record (EHR) system. RESULTS: The
      CCTA registry includes 183 data elements, which involves 20 archetypes. A total
      number of 45 CCTA data elements and EHR data elements have semantic overlap.
      Among them, 38 (84%) CCTA data elements can be found in the 10 reused EHR
      archetypes. These corresponding clinical data can be collected from the EHR
      system directly without transformation. The other 7 (16%) CCTA data elements
      correspond to one coarse-grained EHR data elements, and these clinical data can
      be collected with mapping rules. The results show that the approach can improve
      semantic interoperability of clinical data registry. CONCLUSIONS: Using an
      openEHR based approach to develop clinical data registry can improve the semantic
      interoperability. Meanwhile, some challenges for broader semantic
      interoperability are identified, including domain experts' involvement, archetype
      sharing and reusing, and archetype semantic mapping. Collaborative modeling, easy
      to-use tools, and semantic relationship establishment are potential solutions for
      these challenges. This study provides some experience and insight about clinical
      modeling and clinical data registry development.

PMID- 29589573
TI  - On the Progress of Scanning Transmission Electron Microscopy (STEM) Imaging in a
      Scanning Electron Microscope.
AB  - Transmission electron microscopy (TEM) with low-energy electrons has been
      recognized as an important addition to the family of electron microscopies as it
      may avoid knock-on damage and increase the contrast of weakly scattering objects.
      Scanning electron microscopes (SEMs) are well suited for low-energy electron
      microscopy with maximum electron energies of 30 keV, but they are mainly used for
      topography imaging of bulk samples. Implementation of a scanning transmission
      electron microscopy (STEM) detector and a charge-coupled-device camera for the
      acquisition of on-axis transmission electron diffraction (TED) patterns, in
      combination with recent resolution improvements, make SEMs highly interesting for
      structure analysis of some electron-transparent specimens which are traditionally
      investigated by TEM. A new aspect is correlative SEM, STEM, and TED imaging from
      the same specimen region in a SEM which leads to a wealth of information.
      Simultaneous image acquisition gives information on surface topography, inner
      structure including crystal defects and qualitative material contrast. Lattice
      fringe resolution is obtained in bright-field STEM imaging. The benefits of
      correlative SEM/STEM/TED imaging in a SEM are exemplified by structure analyses
      from representative sample classes such as nanoparticulates and bulk materials.

PMID- 29589575
TI  - Likert Data.

PMID- 29589576
TI  - Note from the editors: World Tuberculosis Day 2018 and Special issue-Screening
      and prevention of infectious diseases in newly arrived migrants in Europe.

PMID- 29589574
TI  - Synchronizing developmental stages in Neotropical catfishes for application in
      germ cell transplantation.
AB  - SummaryThe aim of this study was to describe the effect of temperature on the
      fertilization, early developmental stages, and survival rate of two Neotropical
      catfishes Pimelodus maculatus and Pseudopimelodus mangurus. After fertilization,
      the eggs were incubated at 22 degrees C, 26 degrees C, and 30 degrees C, which
      resulted in fertilization rates of 96.95 +/- 1.79%, 98.74 +/- 0.76%, and 98.44 +/
      0.19% for P. maculatus and 96.10 +/- 1.58%, 98.00 +/- 0.63%, and 94.60 +/- 2.09%
      for P. mangurus, respectively. For P. maculatus, hatching occurred after 22 h 30
      min post-fertilization at 22 degrees C, 16 h 30 min at 26 degrees C, and 11 h 20
      min at 30 degrees C, and the hatching rates were 43.87 +/- 7,46%, 57.57 +/-
      17.49%, and 53.63 +/- 16.27%, respectively. For P. mangurus, hatching occurred
      after 28 h 30 min post-fertilization at 22 degrees C and 17 h 30 min at 26
      degrees C with respective hatching rates of 45.4 +/- 21.02% and 68.1 +/- 12.67%.
      For this species, all embryos incubated at 30 degrees C died before hatching.
      Additionally, for P. maculatus, the larvae from the lower (22 degrees C) and
      higher temperatures (30 degrees C) presented increased abnormality rates, as
      observed in the head, tail and yolk regions. The lowest abnormality rate was
      detected at 26 degrees C, which was considered the optimal incubation temperature
      for both species. The developed protocol enables the manipulation of embryonic
      development, which is important for the application of reproductive
      biotechniques, including chimerism and chromosome-set manipulation. The data
      obtained here are also important for the surrogate propagation of this species as
      P. mangurus was recently categorized as an endangered fish species.

PMID- 29589577
TI  - Hepatitis E virus (HEV) in Scotland: evidence of recent increase in viral
      circulation in humans.
AB  - BackgroundPrevious studies showed low levels of circulating hepatitis E virus
      (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology.
      Methods: Blood donor samples from five Scottish blood centres, the minipools for
      routine HEV screening and liver transplant recipients were tested for HEV
      antibodies and RNA to determine seroprevalence and viraemia. Blood donor data
      were compared with results from previous studies covering 2004-08. Notified
      laboratory-confirmed hepatitis E cases (2009-16) were extracted from national
      surveillance data. Viraemic samples from blood donors (2016) and chronic
      hepatitis E transplant patients (2014-16) were sequenced. Results: Anti-HEV IgG
      seroprevalence varied geographically and was highest in Edinburgh where it
      increased from 4.5% in 2004-08) to 9.3% in 2014-15 (p = 0.001). It was most
      marked in donors < 35 years. HEV RNA was found in 1:2,481 donors, compared with
      1:14,520 in 2011. Notified laboratory-confirmed cases increased by a factor of 15
      between 2011 and 2016, from 13 to 206. In 2011-13, 1 of 329 transplant recipients
      tested positive for acute HEV, compared with six cases of chronic infection
      during 2014-16. Of 10 sequenced viraemic donors eight and all six patients were
      infected with genotype 3 clade 1 virus, common in European pigs. Conclusions: The
      seroprevalence, number of viraemic donors and numbers of notified laboratory
      confirmed cases of HEV in Scotland have all recently increased. The causes of
      this change are unknown, but need further investigation. Clinicians in Scotland,
      particularly those caring for immunocompromised patients, should have a low
      threshold for testing for HEV.

PMID- 29589578
TI  - Universal screening for latent and active tuberculosis (TB) in asylum seeking
      children, Bochum and Hamburg, Germany, September 2015 to November 2016.
AB  - BackgroundIn Germany, the incidence of tuberculosis (TB) in children has been on
      the rise since 2009. High numbers of foreign-born asylum seekers have contributed
      considerably to the disease burden. Therefore, effective screening strategies for
      latent TB infection (LTBI) and active TB in asylum seeking children are needed.
      Aim: Our aim was to investigate the prevalence of LTBI and active TB in asylum
      seeking children up to 15 years of age in two geographic regions in Germany.
      Methods: Screening for TB was performed in children in asylum seeker reception
      centres by tuberculin skin test (TST) or interferon gamma release assay (IGRA).
      Children with positive results were evaluated for active TB. Additionally,
      country of origin, sex, travel time, TB symptoms, TB contact and Bacille Calmette
      Guerin (BCG) vaccination status were registered. Results: Of 968 screened
      children 66 (6.8%) had TB infection (58 LTBI, 8 active TB). LTBI prevalence was
      similar in children from high (Afghanistan) and low (Syria) incidence countries
      (8.7% vs 6.4%). There were no differences regarding sex, age or travel time
      between infected and non-infected children. Children under the age of 6 years
      were at higher risk of progression to active TB (19% vs 2% respectively, p=0,07).
      Most children (7/8) with active TB were asymptomatic at the time of diagnosis.
      None of the children had been knowingly exposed to TB. Conclusions: Asylum
      seeking children from high and low incidence countries are both at risk of
      developing LTBI or active TB. Universal TB screening for all asylum seeking
      children should be considered.

PMID- 29589580
TI  - Challenging the future....

PMID- 29589581
TI  - Hoje e o primeiro dia do resto da minha vida... Today is the first day of the
      rest of my life.

PMID- 29589579
TI  - Field investigation with real-time virus genetic characterisation support of a
      cluster of Ebola virus disease cases in Dubreka, Guinea, April to June 2015.
AB  - On 11 May 2015, the Dubreka prefecture, Guinea, reported nine laboratory
      confirmed cases of Ebola virus disease (EVD). None could be epidemiologically
      linked to cases previously reported in the prefecture. We describe the
      epidemiological and molecular investigations of this event. We used the Dubreka
      EVD registers and the Ebola treatment centre's (ETC) records to characterise
      chains of transmission. Real-time field Ebola virus sequencing was employed to
      support epidemiological results. An epidemiological cluster of 32 cases was
      found, of which 27 were laboratory confirmed, 24 were isolated and 20 died. Real
      time viral sequencing on 12 cases demonstrated SL3 lineage viruses with sequences
      differing by one to three nt inside a single phylogenetic cluster. For isolated
      cases, the average time between symptom onset and ETC referral was 2.8 days
      (interquartile range (IQR): 1-4). The average time between sample collection and
      molecular results' availability was 3 days (IQR: 2-5). In an area with scarce
      resources, the genetic characterisation supported the outbreak investigations in
      real time, linking cases where epidemiological investigation was limited and
      reassuring that the responsible strain was already circulating in Guinea. We
      recommend coupling thorough epidemiological and genomic investigations to control
      EVD clusters.

PMID- 29589582
TI  - Spectrum of CFTR gene sequence variants in a northern Portugal population.
AB  - : In Portugal, the spectrum of Cystic Fibrosis Transmembrane Conductance
      Regulator (CFTR) gene variants is not known. The main objective of this work was
      to determine the type and frequency of CFTR variants in a sample from northern
      Portugal by the complete analysis of the CFTR coding sequencing performed in 512
      Portuguese children. A total of 30 different CFTR sequence variants, already
      reported as cystic fibrosis (CF) or CFTR related disorders variants, were
      detected. Ninety-two children (18.0%; 95%CI: 14.7-21.6) were found to be carriers
      of one sequence variant and 8 (1.6%; 95%CI: 0.7-3.1) had two sequence variants.
      Taking into consideration only variants that may cause CF when combined with a
      pathogenic CF variant, the CF pathogenic variant carrier frequency was 3.3%
      (95%CI: 1.9-5.3). One (0.2%; 95%CI: 0.01-0.7) child presented two CF pathogenic
      variants. CONCLUSIONS: The majority of CFTR variants detected have been
      associated with a less severe CF phenotype. A wide spectrum of CFTR variants was
      identified, confirming the highest CFTR allelic heterogeneity previously reported
      in Mediterranean country. Additionally, better knowledge about the CFTR sequence
      variation spectrum may contribute to more efficient genetic testing in the
      Portuguese population.

PMID- 29589583
TI  - Central alveolar hypoventilation due to progressive multifocal
      leukoencephalopathy.

PMID- 29589584
TI  - Mediastinal sarcoid-like reaction in cancer patients.

PMID- 29589585
TI  - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia mimicking metastatic
      disease.

PMID- 29589586
TI  - An Increase in Tryptase on the First Day of Hymenoptera Venom Immunotherapy Might
      Be a Predictor of Future Systemic Reactions During Treatment.
AB  - BACKGROUND AND OBJECTIVE: Serum tryptase (ST) decreases during long-term venom
      immunotherapy (VIT). ST also exhibits a circadian variation, with a small
      decrease after sting challenge. Both findings have been related to successful
      VIT. Objective: To assess whether variation (increase or decrease) in ST on the
      first day of VIT is associated with the likelihood of future systemic adverse
      reactions (SARs) during treatment. METHODS: We prospectively studied patients who
      underwent cluster VIT, which was continued for at least 6 months. ST was measured
      on the first day of VIT, before the first dose (pre-IT tryptase) and after the
      last dose (post-IT tryptase). Differences between patient groups (with and
      without SAR) were analyzed. RESULTS: A total of 160 courses of VIT were
      administered to 150 patients. The median baseline ST value was 4.3 MUg/L. A total
      of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with
      SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the
      median increment was 19% in these patients. We found a significant association
      between the increase in ST on the first day of VIT and future SARs (risk ratio,
      7.6). This elevation was independent of the scheduled VIT day, severity of the
      SAR, and baseline ST value. CONCLUSIONS: A slight increase in tryptase on the
      first day of VIT is an independent variable that is strongly related to a high
      risk of future SAR. This simple biomarker could improve patient safety.

PMID- 29589587
TI  - Immune activation, inflammation and HIV DNA after 96-weeks of ATV/r monotherapy:
      a MODAt substudy.

PMID- 29589588
TI  - Two-leg ladder systems with dipole-dipole Fermion interactions.
AB  - The ground-state phase diagram of a two-leg fermionic dipolar ladder with inter
      site interactions is studied using density matrix renormalization group (DMRG)
      techniques. We use a state-of-the-art implementation of the DMRG algorithm and
      finite size scaling to simulate large system sizes with high accuracy. We also
      consider two different model systems and explore stable phases in half and
      quarter filling factors. We find that in the half filling, the charge and spin
      gaps emerge in a finite value of the dipole-dipole and on-site interactions. In
      the quarter filling case, s-wave superconducting state, charge density wave,
      homogenous insulating and phase separation phases occur depend on the interaction
      values. Moreover, in the dipole-dipole interaction, the D-Mott phase emerges when
      the hopping terms along the chain and rung are the same, whereas, this phase has
      been only proposed for the anisotropic Hubbard model. In the half filling case,
      on the other hand, there is either charge-density wave or charged Mott order
      phase depends on the orientation of the dipole moments of the particles with
      respect to the ladder geometry.

PMID- 29589589
TI  - Chromosome aberrations in workers occupationally exposed to tritium.
AB  - This paper reports the findings of an historical chromosome analysis for unstable
      aberrations, undertaken on 34 nuclear workers with monitored exposure to tritium.
      The mean recorded beta-particle dose from tritium was 9.33 mGy (range 0.25-79.71
      mGy) and the mean occupational dose from external, mainly gamma-ray, irradiation
      was 1.94 mGy (range 0.00-7.71 mGy). The dicentric frequency of 1.91 +/- 0.53 * 10
      3 per cell was significantly raised, in comparison with that of 0.61 +/- 0.30 *
      10-3 per cell for a group of 66 comparable worker controls unexposed to
      occupational radiation. The frequency of total aberrations was also significantly
      higher in the tritium workers. Comparisons with in vitro studies indicate that at
      these dose levels an increase in aberration frequency is not expected. However,
      the available historical tritium dose records were produced for the purposes of
      radiological protection and based on a methodology that has since been updated,
      so tritium doses are subject to considerable uncertainty. It is therefore
      recommended that, if possible, tritium doses are reassessed using information on
      historical recording practices in combination with current dosimetry methodology,
      and that further chromosome studies are undertaken using modern FISH techniques
      to establish stable aberration frequencies, as these will provide information on
      a cumulative biological effect.

PMID- 29589590
TI  - Editorial: Protection of the Public Following the 'Kyshtym Accident' in 1957.

PMID- 29589591
TI  - Phase transitions and magnetization of the mixed-spin Ising-Heisenberg double
      sawtooth frustrated ladder.
AB  - The mixed spin-(1,1/2) Ising-Heisenberg double sawtooth ladder containing a
      mixture of both spin-1 and spin-1/2 nodal atoms, and the spin-1/2 interstitial
      dimers are approximately solved by the transfer-matrix method. Here, we study in
      detail the ground-state phase diagrams, also influences of the bilinear exchange
      coupling on the rungs and cyclic four-spin exchange interaction in square
      plaquette of each block on the magnetization and magnetic susceptibility of the
      suggested ladder at low temperature. Such a double sawtooth ladder may be found
      in a Shastry-Sutherland lattice-type. In spite of the spin ordering of odd and
      even blocks being different from each other, due to the commutation relation
      between all different block Hamiltonians, phase diagrams, magnetization behavior
      and thermodynamic properties of the model are the same for odd and even blocks.
      We show that at low temperature, both exchange couplings can change the quality
      and quantity of the magnetization plateaus versus the magnetic field changes.
      Specially, we find a new magnetization plateau [Formula: see text] for this
      model. Besides, we examine the magnetic susceptibility and specific heat of the
      model in detail. It is proven that behaviors of the magnetization and the
      magnetic susceptibility coincide at low temperature. The specific heat displays
      diverse temperature dependencies, which include a Schottky-type peak at a special
      temperature interval. We observe that with increase of the bilinear exchange
      coupling on the rungs, second peak temperature dependence grows.

PMID- 29589592
TI  - Developing a hippocampal neural prosthetic to facilitate human memory encoding
      and recall.
AB  - OBJECTIVE: We demonstrate here the first successful implementation in humans of a
      proof-of-concept system for restoring and improving memory function via
      facilitation of memory encoding using the patient's own hippocampal
      spatiotemporal neural codes for memory. Memory in humans is subject to disruption
      by drugs, disease and brain injury, yet previous attempts to restore or rescue
      memory function in humans typically involved only nonspecific, modulation of
      brain areas and neural systems related to memory retrieval. APPROACH: We have
      constructed a model of processes by which the hippocampus encodes memory items
      via spatiotemporal firing of neural ensembles that underlie the successful
      encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model
      of hippocampal CA3 and CA1 neural firing is computed that predicts activation
      patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to
      sample (DMS) human short-term memory task. MAIN RESULTS: MIMO model-derived
      electrical stimulation delivered to the same CA1 locations during the sample
      phase of DMS trials facilitated short-term/working memory by 37% during the task.
      Longer term memory retention was also tested in the same human subjects with a
      delayed recognition (DR) task that utilized images from the DMS task, along with
      images that were not from the task. Across the subjects, the stimulated trials
      exhibited significant improvement (35%) in both short-term and long-term
      retention of visual information. SIGNIFICANCE: These results demonstrate the
      facilitation of memory encoding which is an important feature for the
      construction of an implantable neural prosthetic to improve human memory.

PMID- 29589593
TI  - Fermi-edge singularity and the functional renormalization group.
AB  - We study the Fermi-edge singularity, describing the response of a degenerate
      electron system to optical excitation, in the framework of the functional
      renormalization group (fRG). Results for the (interband) particle-hole
      susceptibility from various implementations of fRG (one- and two-particle
      irreducible, multi-channel Hubbard-Stratonovich, flowing susceptibility) are
      compared to the summation of all leading logarithmic (log) diagrams, achieved by
      a (first-order) solution of the parquet equations. For the (zero-dimensional)
      special case of the x-ray-edge singularity, we show that the leading log formula
      can be analytically reproduced in a consistent way from a truncated, one-loop fRG
      flow. However, reviewing the underlying diagrammatic structure, we show that this
      derivation relies on fortuitous partial cancellations special to the form of and
      accuracy applied to the x-ray-edge singularity and does not generalize.

PMID- 29589595
TI  - Cell signalling: DNA damage puts p38 under the UV light.

PMID- 29589594
TI  - Mercaptoethanol Protects the Aorta from Dissection by Inhibiting Oxidative
      Stress, Inflammation, and Extracellular Matrix Degeneration in a Mouse Model.
AB  - BACKGROUND The aims of this study were to investigate the effects of
      mercaptoethanol treatment on the expression of mediators of oxidative stress,
      inflammation, and extracellular matrix (ECM) degeneration in a mouse aortic
      dissection (AD) model. MATERIAL AND METHODS Twenty-four 8-month-old C57BL/6J mice
      were divided into three groups and studied for two weeks: 1) the aortic
      dissection (AD) Model group (N=8) underwent intraperitoneal injection of
      angiotensin II (Ang II) (5 ml/kg) three times every 24 h; 2) the mercaptoethanol
      Treated group (N=8) were given oral mercaptoethanol (2.5 mM); the Normal group
      (N=8) underwent intraperitoneal injection of noradrenaline (5 mg/kg) three times
      every 24 h. Sections of mouse aorta were prepared for histology with hematoxylin
      and eosin (H&E) staining; immunohistochemistry was performed to detect levels of:
      nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), nuclear factor kappaB (NF
      kappaB), p65, superoxide dismutase-1 (SOD1), glutamate cysteine ligase catalytic
      subunit (GCLC), tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL
      1beta), and matrix metalloproteinase-9 (MMP9). Quantitative reverse transcription
      polymerase chain reaction (RT-PCR) evaluated mRNA expression of SOD1, GCLC, TNF
      alpha, IL-1beta, and MMP9. RESULTS Mercaptoethanol treatment inhibited Ang II
      induced aortic dissection in AD mice, as shown histologically. Mercaptoethanol
      treatment reduced the expression levels of NFE2L2, NF-kappaB, p65, TNF-alpha, IL
      1beta and increased the expression levels of SOD1, MMP9, and GCLC. CONCLUSIONS In
      an AD mouse model, mercaptoethanol treatment inhibited thoracic and abdominal
      aortic dissection and reduced aortic tissue expression of mediators of oxidative
      stress and inflammation and increased the activation of ECM signaling pathways.

PMID- 29589597
TI  - Correction: The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in
      Conformational Switching: The Critical Role of Ionic Strength.
AB  - [This corrects the article on p. 755 in vol. 8, PMID: 29163152.].

PMID- 29589596
TI  - CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic
      rats.
AB  - Nephropathy is one of the most severe complications of diabetic patients. The
      therapeutic strategies for diabetic patients should not only focus on the control
      of blood glucose but also pay attention to the occurrence of diabetic nephropathy
      (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the
      clinical application of CoQ10 has been limited because of its low water
      solubility and non-specific distribution. Liposomes were supposed to be an
      effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated
      into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The
      CoQ10-LIP exhibited a small hydrodynamic diameter (180 +/- 2.1 nm) and negative
      zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound
      mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10
      in kidney. In early stage of diabetic mellitus (DM), rats were administrated with
      CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results
      revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and
      function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was
      highly associated with protecting podocyte, promoting vascular repair and
      inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might
      be a potential strategy to prevent occurrence of DN.

PMID- 29589598
TI  - Erratum: Profile of buparlisib and its potential in the treatment of breast
      cancer: evidence to date [Corrigendum].
AB  - [This corrects the article on p. 23 in vol. 10, PMID: 29430197.].

PMID- 29589599
TI  - Continuous Monitoring of Respiratory Rate on General Wards What might the
      implications be for Clinical Practice?
AB  - A high respiratory rate is a significant predictor of deterioration. The accuracy
      of measurements has been questioned. We performed a prospective observational
      study of automated electronic respiratory rate measurements and compared
      measurements with electronic counts obtained in the 10 minutes prior to the
      manual measurement. For 182 patients 1331 matching measurements could be
      compared. The mean age of these patients was 68 (SD 14) years. 96 (53%) of
      patients were female. While mean and median measurements were similar frequency
      distributions were significantly different. Manual measurements were markedly
      lower than electronic measurements in patients with higher respiratory rates.
      While electronic measurements are likely to be more reliable clinical
      implications require further investigation to clarify whether existing algorithms
      including Early Warning Scores will need adjustment.

PMID- 29589600
TI  - Can an acute admission to hospital be an opportunity for healthcare professionals
      to provide physical activity advice? A qualitative study of patients'
      perspectives.
AB  - Physical inactivity causes morbidity, mortality and healthcare expenditure. A
      minority of people undertake sufficient physical activity to meet the DoH
      recommendations. NICE has determined that brief advice in primary care is
      costeffective in increasing physical activity levels but there is no current
      recommendation for secondary care. Acute medical admissions represent "teachable
      moments" where patients might be receptive to advice. Qualitative methodology was
      used to determine the perspectives of acute medical in-patients on their
      willingness to receive physical activity advice and on its format and delivery.
      Most participants thought physical activity should be discussed by health care
      professionals if it related to the reason they were admitted to hospital but
      wanted individually-tailored advice on overcoming their specific barriers to
      physical activity.

PMID- 29589601
TI  - Relationship of the clinical acuity & complexity to the outcome of an emergency
      medical admission.
AB  - BACKGROUND: An Illness Severity and Co-morbidity composite score can predict 30
      day mortality outcome. METHODS: We computed a summary risk score (RS) for
      emergency medical admissions and used cluster analysis to define four subsets
      Results: Four cluster groups were defined. Cluster 1 - RS 7 points (IQR 5, 8)
      Cluster 2 - 9 (IQR 8, 11), Cluster 3 - 12 (IQR 11, 13) and Cluster 4 - 14 (IQR
      13, 15). Clusters predicted 30-day in hospital mortality OR 1.86 (95%CI: 1.82,
      1.92); respective rates 1.4% (95% CI: 1.3%, 1.6%), 3.4% (95% CI: 3.1%, 3.6%),
      7.8% (95% CI: 7.5%, 8.1%) and 16.5% (95% CI: 15.7%, 17.2%). CONCLUSION: Cluster
      grouping of Risk Score was age related; strongest outcome determinant was Acute
      Illness Severity.

PMID- 29589602
TI  - The predictive value of leucocyte progression for one-week mortality on acutely
      admitted medical patients to the emergency department.
AB  - OBJECTIVE: To clarify if leucocyte count progression can predict one-week
      mortality in unselected medical patients admitted to the emergency department.
      Additionally, we investigated the importance of leucocyte count progression for
      admission to the intensive care unit and length of stay. METHOD: This
      retrospective cohort study uses data collected in two phases from patients
      admitted through the emergency department at Hospital of South West Jutland. Upon
      admission, a nurse recorded the primary complaint and vital signs and registered
      these along with demographic information. Blood test results were subsequently
      extracted from the hospital's computer systems. Patients were separated into
      three groups according to the development in their leucocyte count from the day
      of admission to the day after. RESULTS: The total cohort was 5894 patients; 30.5%
      remained after exclusion. Median age was 71, and 50.3% were female. Using
      logistic regression, we found significantly lower one-week mortality with falling
      leucocyte count progression, even when controlling for confounders. A decreasing
      leucocyte count had a sensitivity for one-week mortality of 65%, specificity of
      62%, positive predictive value of 4%, and negative predictive value of 99%.
      Difference in admission to the intensive care unit was non-significant between
      the three groups. Difference in length of stay was significant, but with one day
      difference, the clinical significance is questionable. CONCLUSION: Leucocyte
      count progression is not sensitive enough to predict one-week mortality, nor
      specific enough to discount it. It is important for physicians to be aware of
      this to avoid faulty assessments based on imprecise assumptions.

PMID- 29589603
TI  - Acute kidney injury in kidney transplant patients.
AB  - Managing kidney transplant patients in an acute medical unit can be challenging,
      as patients have a single functioning kidney, underlying chronic kidney disease,
      and are immunosuppressed. Transplant patients develop AKI for all usual reasons
      but the differential diagnosis is wider and includes specific problems, such as
      obstruction of a single functioning kidney, vascular thrombosis, rejection, drug
      toxicity and drug-induced thrombotic microangiopathy. Septic AKI is common but
      again, the differential diagnosis of sepsis is wider. Transplant patients are at
      higher risk of developing both community and opportunistic infections, especially
      in the first year after the transplant or after any increase in immunosuppressive
      medication. In addition, there is always a risk of rejection, especially in case
      of reduction of immunosuppressive medications. Therefore, any change in the
      immunosuppressive therapy should to be discussed with the transplant team to
      achieve an appropriate balance between avoiding rejection and preventing
      opportunistic infections.

PMID- 29589604
TI  - Nephrotic syndrome in adults.
AB  - Nephrotic syndrome is an important presentation of glomerular disease
      characterised by heavy proteinuria, hypoalbuminaemia and oedema. The differential
      diagnosis of the underlying condition is wide including primary renal disorders
      and secondary diseases such as malignancy, infection, diabetes and amyloid.
      Presentations to acute medicine may be with hypervolaemia, complications of the
      nephrotic state (such as venous thromboembolism), or complications of therapy
      (such as infection). Early recognition of nephrotic syndrome is possible through
      simple urinalysis for protein and testing serum albumin, although a high index of
      suspicion is sometimes required in patients with comorbidities including
      potentially distracting cardiac or hepatic diseases.

PMID- 29589605
TI  - Managing thyrotoxicosis in the acute medical setting.
AB  - Thyrotoxicosis is common and can present in numerous ways with patients
      exhibiting a myriad of symptoms and signs. It affects around 1 in 2000 people
      annually in Europe1. The thyroid gland produces two thyroid hormones - thyroxine
      (T4) and triiodothyronine (T3). Thyroxine is inactive and is converted by the
      tissues and organs that need it into tri-iodothyronine. In health, the production
      of these thyroid hormones is tightly regulated by the secretion of thyroid
      stimulating hormone (TSH; thyrotropin) from the pituitary gland. The term
      'thyrotoxicosis' refers to the clinical manifestations of hyperthyroidism.

PMID- 29589606
TI  - A young breathless patient.
AB  - A 34-year-old gentleman, with a background of osteoarthritis, presented to the
      Acute Medical Unit with a short history of breathlessness. He had returned from
      holiday to the United States five days previously. Since return, he had
      complained of myalgia, sore throat, a non-productive cough, mild anorexia and
      fevers at home. More acutely, prompting his presentation to hospital, was acute
      dyspnoea, which was sudden onset, with some central anterior chest discomfort and
      worse lying flat.

PMID- 29589607
TI  - A Catastrophic Consequence of Cramp.
AB  - Quinine has long been used for the treatment of conditions such as malaria and
      leg cramps, and is also present at low levels in some beverages; however, it can
      cause serious side effects. We describe a patient who developed severe
      haemolysis, thrombocytopaenia, and acute kidney injury following the ingestion of
      a single dose of quinine. This case demonstrates the importance of awareness of
      such potentially life-threatening consequences of exposure to this agent.

PMID- 29589608
TI  - Insight into selectivity: uptake studies of radionuclides 90Sr2+, 137Cs+, and
      233UO22+ with bis-amidoxime polymers.
AB  - Uptake characteristics of a bis-amidoximated polymer are presented for 90Sr2+,
      137Cs+, and 233UO22+ to assess rational ligand design and polymer engineering
      efforts applied to selective uranium extraction. Functionalized with the bis
      amidoxime diaryl ether ligand at a loading of 1.98 mmol per gram of polymer, the
      polymer was found to sorb uranium from a pH 6 solution with a separation factor
      (alpha) over cesium of 1.2 * 103. Strontium uptake was negligible throughout the
      pH range studied whereas cesium uptake averaged <30%. Moreover, at near neutral
      pH, the sorbent was able to purify water to below the United States' set maximum
      contaminant level for uranium, decreasing the U concentration from 330 ppb to
      below 3 ppb in 30 minutes. Density functional theory (DFT) calculations, used to
      probe the nature of the metal-bis-amidoxime interaction, help inform the
      empirically realized uptake selectivity.

PMID- 29589610
TI  - Solvent-free synthesis of monodisperse Cu nanoparticles by thermal decomposition
      of an oleylamine-coordinated Cu oxalate complex.
AB  - Cu nanoparticles (NPs) are widely used in numerous applications because of their
      unique optical, catalytic, and electrical properties. However, the synthesis of
      monodisperse Cu NPs often involves harmful reducing agents under an inert
      atmosphere in a solution with low Cu ion concentrations. In this study,
      monodisperse Cu NPs were synthesized by the thermal decomposition of an
      oleylamine-coordinated Cu oxalate (Cu(ox)) complex (OA-Cu(ox)) in oleylamine in
      air with no reducing agent. The structure of OA-Cu(ox) was analyzed using Fourier
      transform infrared spectroscopy. The decomposition temperature of the oxalate ion
      was reduced to 130  degrees C from that of Cu(ox) (300  degrees C) because of the
      coordination of the primary amino group of oleylamine with the Cu ion of Cu(ox).
      Furthermore, the decomposition temperature of OA-Cu(ox) strongly affected the
      size distribution of the synthesized Cu NPs. Monodisperse Cu NPs were
      successfully synthesized by the thermal decomposition of OA-Cu(ox) at
      temperatures higher than 240  degrees C with high yield (~90%). The synthesized
      Cu NPs were readily dispersed in toluene.

PMID- 29589609
TI  - Upregulating mTOR/ERK signaling with leonurine for promoting angiogenesis and
      tissue regeneration in a full-thickness cutaneous wound model.
AB  - Wound therapy remains a clinical challenge due to the poor vascularization during
      the healing process and the high demand to achieve functional and aesthetically
      satisfactory scars. Newly-formed blood vessels are necessary for wound healing
      since they can deliver nutrients and oxygen to the wound area. In this study, the
      role of leonurine (LN), a traditional Chinese medicine isolated from Herba
      leonuri, in promoting angiogenesis and its function in wound healing have been
      investigated. The results of co-culture with human umbilical vein endothelial
      cells (HUVECs) demonstrated that LN treatment (5-20 MUM) could promote the
      proliferation and migration and enhance the ability of in vitro angiogenesis
      through up-regulating the mTOR/ERK signaling pathway. Furthermore, a full
      thickness cutaneous wound model was used to investigate the healing effect of LN
      in vivo. Intragastric administration of 20 mg per kg per day LN stimulated the
      regeneration of more blood vessels at the wound sites, which confirmed the in
      vitro results of promoting angiogenesis. Due to fast vascularization, the
      collagen matrix deposition and remodeling processes were also accelerated in LN
      treated wounds, resulting in efficient wound healing. In summary, LN promoted
      angiogenesis of endothelial cells in vitro by activating the mTOR/ERK pathway,
      and could efficiently enhance the angiogenesis and collagen deposition of the
      regenerated tissue, together with facilitating the wound healing process in vivo.
      This study provides evidence for LN-stimulated angiogenesis and tissue
      regeneration in skin wounds, especially in ischemic wounds.

PMID- 29589611
TI  - Experimental evidence of TICT state in 4-piperidinyl-1,8-naphthalimide - a
      kinetic and mechanistic study.
AB  - The excited state processes in N-propyl-4-piperidinyl-1,8-naphthalimide have been
      studied by measuring its fluorescence spectra and decay curves in solvents of
      different polarity and viscosity and also in a frozen solvent glass. The results
      unanimously proved the formation of a dark twisted intramolecular charge transfer
      (TICT) state from the emissive charge transfer (CT) species, the direct product
      of excitation. The rate coefficients of the TICT process and the deactivations of
      the CT and TICT species were determined, using a reversible two-state kinetic
      model. The temperature dependence of the kinetic data was consistent with a
      kinetic barrier consisting of three terms, the inherent barrier of the reaction,
      and the contributions of the solute-solvent interactions related to the solvent
      viscosity and polarity. The potential energy surfaces were calculated in the S0
      and the S1 states along the coordinate of turning motion which was conclusive
      concerning the direction of the twisting and indicated a possible conformational
      change of the piperidinyl unit. The theoretical calculations confirmed that the
      TICT species is dark and has a stronger charge transfer character compared to the
      CT state.

PMID- 29589612
TI  - One-step synthesis of MnS/MoS2/C through the calcination and sulfurization of a
      bi-metal-organic framework for a high-performance supercapacitor and its
      photocurrent investigation.
AB  - Based on a Mn/Mo-metal organic framework (MOF) precursor, [Mn(4,4'-bipyridine)0.5
      MoO4].1.5H2O, a MnS/MoS2/C hybrid was synthesized through a calcination and
      sulfurization approach and it is mainly constituted by MoS2/C nanorods and
      MnS/MoS2/C nanoflakes. The MnS/MoS2/C hybrid delivers a high specific capacitance
      of 1162 F g-1 at 0.5 A g-1 in 2 M KOH electrolyte, and it possesses a good rate
      capacity with a retention of 75.7% (880 F g-1) at 10 A g-1, which is due to the
      synergetic effects of the components MnS, MoS2 and carbon matrix in the hybrid
      material. The carbon matrix in the hybrid material can not only anchor the active
      components of MnS and MoS2, but also transport electrons efficiently. The
      completely exposed Mo and S edges on the preferential 2H-(002) and 3R-(003)
      facets of MoS2 are beneficial for ion adsorption and electrochemical reaction. An
      asymmetric supercapacitor constructed by the MnS/MoS2/C hybrid (positive
      electrode) and activated carbon (AC) (negative electrode) exhibited a capacitance
      retention of 81% after 5000 galvanostatic charge-discharge cycles (GCD). During
      the GCD process, the metal sulfides were probably transformed into metal
      hydroxides in the presence of OH- electrolyte ions. In addition, the MnS/MoS2/C
      hybrid exhibits a visible light-driven photocurrent response, and DFT calculation
      proves that it is attributed to the semiconducting feature of MoS2 in the hybrid.

PMID- 29589613
TI  - All-inorganic CsPbBr3 perovskite quantum dots embedded in dual-mesoporous silica
      with moisture resistance for two-photon-pumped plasmonic nanoLasers.
AB  - Lead halide perovskite nanocrystals with efficient two-photon absorption and ease
      of achieving population inversion have been recognized as good candidates to
      achieve frequency up-conversion for biophotonics applications, but suffer from
      the limitation of the miniaturization of the device and its corresponding poor
      stability when exposed to atmospheric moisture. Here we demonstrate the
      miniaturization of plasmonic nanolasers via embedding perovskite quantum dots
      (QDs) in rationally designed dual-mesoporous silica with gold nanocore. The
      nanocomposite supports resonant surface plasmon-polaritons (SPPs), which overlap
      both spatially and spectrally with the CsPbBr3 QDs. The outcoupling between
      surface plasmon oscillations and photonics modes within a wavelength range
      completely overcomes the loss of localized surface plasmons, and finally
      contributes to a novel application of two-photon-pumped nanolasers. Large optical
      gain under two-photon excitation was observed as a result of resonant energy
      transfer from excited perovskite QDs to surface plasmon oscillations and
      stimulated emission of surface plasmons in a luminous mode. The outmost organic
      inorganic hybrid shells of the dual-mesoporous silica nanocomposites act as a
      protective layer of the perovskite QDs against water and endow the nanocomposites
      with superhydrophobicity. This work provides an alternative inspiration for the
      design of new two-photon pumped nanolasers.

PMID- 29589614
TI  - An in situ spectroelectrochemical study on the orientation changes of an
      [FeiiiLN2O3] metallosurfactant deposited as LB Films on gold electrode surfaces.
AB  - In this paper we analyze the changes in molecular orientation triggered by
      electrochemical reduction of an iron-containing surfactant in Langmuir-Blodgett
      films deposited onto gold electrodes. The metallosurfactant [Feiii(LN2O3)] (1) is
      an established molecular rectifier capable of unidirectional electron transfer
      between two electrodes. A gradual decrease in the activity is observed in
      sequential current vs. potential curves upon repeated cycles. Here we evaluate
      the redox response associated with the reduction of the Feiii/Feii couple in a
      single monolayer, as well as in a 5-layer LB film of 1. We use polarization
      modulation infrared reflection absorption spectroscopy (PM IRRAS) to follow
      structural and orientation changes associated with such applied potential scans.
      We observe that the reduction of the Fe center becomes increasingly irreversible
      because an Fe-Ophenolate bond is cleaved. This transformation is accompanied by
      an almost vertical change in the orientation of metallosurfactant molecules in LB
      films.

PMID- 29589615
TI  - Integration of Au nanoparticles with a g-C3N4 based heterostructure: switching
      charge transfer from type-II to Z-scheme for enhanced visible light
      photocatalysis.
AB  - Here, we demonstrate that a type-II g-C3N4 nanosheet (CNNS)/W18O49
      heterostructure composite can be switched to Z-scheme through the deposition of
      Au nanoparticles (NPs) on the surface of CNNS. As a direct result, the designed
      Au/CNNS/W18O49 heterostructure shows enhanced photocatalytic performance for
      Cr(vi) reduction than the CNNS/W18O49 heterostructure and single components (CNNS
      and W18O49) under visible light irradiation.

PMID- 29589616
TI  - Correction: Highly photoluminescent copper carbene complexes based on prompt
      rather than delayed fluorescence.
AB  - Correction for 'Highly photoluminescent copper carbene complexes based on prompt
      rather than delayed fluorescence' by Alexander S. Romanov et al., Chem. Commun.,
      2016, 52, 6379-6382.

PMID- 29589617
TI  - Exploring the methanol decomposition mechanism on the Pt3Ni(100) surface: a
      periodic density functional theory study.
AB  - The detailed mechanism of the methanol decomposition reaction (MDR) on the
      Pt3Ni(100) surface is studied based on self-consistent periodic density
      functional theory calculations. The geometries and energies of methanol and its
      intermediates involved in MDR are analyzed, and the reaction network is
      constructed to illustrate the MDR mechanisms. The possible pathways through
      initial scission of the O-H, C-H, and C-O bonds in methanol are discussed based
      on the steric effect and electronic structure of the related transition states
      and the Bronsted-Evans-Polanyi (BEP) relationships. The initial scission of the O
      H bond is favorable and bears the lowest energy barrier among the three
      decomposition modes (initial scission of O-H, C-H, and C-O bonds). Potential
      energy surface (PES) analysis confirmed that although the initial scission of the
      O-H bond is more favorable than scission of the C-H bond, the initial scission of
      the C-H bond can actually occur because of the very low energy barrier for
      further dehydrogenation of CH2OH via scission of its O-H bond. Thus, the pathway
      for MDR on the Pt3Ni(100) surface may possibly proceed via two competitive
      pathways: CH3OH -> CH3O -> CH2O -> CHO -> CO and CH3OH -> CH2OH -> CH2O -> CHO ->
      CO. Comparisons between the current results and the MDR on other systems are made
      and show that Pt3Ni(100) can be a good catalyst for MDR.

PMID- 29589618
TI  - Safety considerations of plant polysaccharides for food use: a case study on
      phenolic-rich softwood galactoglucomannan extract.
AB  - A growing population and concern over the sufficiency of natural resources for
      feeding this population have motivated researchers and industries to search for
      alternative and complementary sources of food ingredients and additives. Numerous
      plant species and parts of plants are explored as raw materials for food
      production. An interesting example is wood; to date, only a few wood-based
      additives or ingredients are authorized for food use. Wood hemicelluloses, such
      as softwood galactoglucomannans (GGM), constitute an abundant bioresource that
      shows a high potential functionality in edible materials. Spruce GGM acts as a
      multi-functional emulsion stabilizer, and it could be used in various processed
      food products, replacing less effective, conventional emulsifiers. Before new
      materials can be released into the food market, their safety must be evaluated,
      according to the Novel Food regulation. This review focuses on the safety aspects
      that must be considered before polysaccharide- and phenolic-rich plant extracts
      can be awarded the status of authorized food ingredients. In this review, GGM is
      presented as a case study and examples are given of plant-based polysaccharides
      that are already authorized for food purposes. The legislation regarding Novel
      Food ingredients in Europe is also briefly reviewed.

PMID- 29589619
TI  - One-pot synthesis of N-doped carbon dots by pyrolyzing the gel composed of
      ethanolamine and 1-carboxyethyl-3-methylimidazolium chloride and their selective
      fluorescence sensing for Cr(vi) ions.
AB  - N-Doped carbon dots (CDs) were directly synthesized with a high yield of 21.85%
      by one-pot pyrolysis of a gel composed of ethanolamine and 1-carboxyethyl-3
      methylimidazolium chloride at 220  degrees C for 2 h. The as-synthesized CDs with
      a mean particle size of 7.8 nm were uniform, amorphous, and abundant in nitrogen
      content (23.15 wt%) and surface groups such as amide and hydroxyl. Thus, the CDs
      exhibited good water-solubility, bright blue excitation- and pH-dependent
      fluorescence with a quantum yield of 17.93%, and high ionic strength tolerance.
      In addition, a CD-based fluorescent sensor towards Cr(vi) ions with favorable
      sensitivity and selectivity was constructed based on the inner filter effect. Two
      good linear relationships between the concentration of Cr(vi) ions and the PL
      quenching efficiency were obtained in the ranges from 0.2 to 2 (R2 = 0.9965) and
      2-40 MUM (R2 = 0.9918), and the limits of detection (LOD = 3sigma/S) were
      calculated as 0.018 and 0.25 MUM, respectively. Importantly, this sensor was
      solid and capable of rapidly detecting Cr(vi) ions in tap water with detection
      ranges of 0.2-2 (R2 = 0.9817) and 2-60 MUM (R2 = 0.9902), LODs of 0.048 and 0.40
      MUM, and recoveries of 102.1-106%.

PMID- 29589620
TI  - Facile reactions of gold(i) complexes with tri(tert-butyl)azadiboriridine.
AB  - Direct structural evidence for group 11 metal-mediated B-B bond activation was
      obtained from reactions of tri(tert-butyl)azadiboriridine (1) with AuCl(L)
      complexes. The AuCl(SMe2) reaction afforded [eta2-B,B-B(tBu)N(tBu)B(tBu)]AuCl (2)
      by ligand displacement. More donating phosphines as co-ligands led to B-B bond
      cleavage accompanied by either halide or L migration to form boron-gold complexes
      3 (L = PPh3) and 4 (L = PMe3). A similar product 5, which is isostructural to 4,
      was obtained by the addition of dimethylaminopyridine (DMAP) to 2-4. Complexes 2
      5 constitute rare examples of metal complexes bearing two Lewis acidic centres.
      The effect of the boryl ligand was demonstrated in the formation of a gold(i)
      complex 6 bearing a 5-membered heterocycle from 3 and tert-butylisonitrile.
      Plausible reaction mechanisms that led to these complexes and their bonding
      situation were explored computationally at the DFT level.

PMID- 29589621
TI  - Cyanotrifluoromethylthiolation of unactivated dialkyl-substituted alkynes via
      cyano migration: synthesis of trifluoromethylthiolated acrylonitriles.
AB  - Herein a novel, elusive cyanotrifluoromethylthiolation of unactivated dialkyl
      substituted alkynes is reported. Taking advantage of the intramolecular cyano
      migration strategy, the reaction proceeds stereoselectively to deliver E-olefinic
      products. A variety of tetrasubstituted trifluoromethylthiolated acrylonitriles
      are afforded in modest to good yields.

PMID- 29589622
TI  - Orientation direction dependency of cavitation in pre-oriented isotactic
      polypropylene at large strains.
AB  - Orientation direction dependency of whitening activated at large strains was
      studied using four pre-oriented isotactic polypropylene (iPP) samples with
      different molecular weights stretched along different directions with respect to
      the pre-orientation (0 degrees , 45 degrees , and 90 degrees ) by means of in
      situ wide-, small-, and ultra-small-angle X-ray scattering techniques. A
      macroscopic fracture of iPP materials was also observed following the stress
      whitening at large strains. These two associated processes in pre-oriented iPP
      samples at elevated temperatures were found to be governed by not only the
      molecular weight of iPP but also the pre-orientation direction. For a certain pre
      orientation direction of iPP, both the critical stress of cavitation induced
      whitening and failure stress increased with increasing molecular weight. For one
      given molecular weight, the pre-oriented iPP showed the smallest critical stress
      for whitening and failure stress along the pre-orientation direction (0 degrees )
      while the samples displayed larger values for the same behaviors when stretched
      at 45 degrees  or 90 degrees  with respect to the pre-orientation direction. Such
      behavior suggested that oriented amorphous networks, with different mechanical
      strengths, can be generated during the second deformation processes in these pre
      oriented iPP samples. The evolution of inter-fibrillar tie chains in highly
      oriented amorphous networks was considered as the main factor controlling the
      response of the inner network to the external stress since the cavitation-induced
      whitening activated at large strains was caused by the failure of load bearing
      inter-fibrillar tie chains in the oriented amorphous network.

PMID- 29589623
TI  - Nanoparticle-cell interactions induced apoptosis: a case study with
      nanoconjugated epidermal growth factor.
AB  - In addition to the intrinsic toxicity associated with the chemical composition of
      nanoparticles (NP) and their ligands, biofunctionalized NP can perturb specific
      cellular processes through NP-cell interactions and induce programmed cell death
      (apoptosis). In the case of the epidermal growth factor (EGF), nanoconjugation
      has been shown to enhance the apoptotic efficacy of the ligand, but the critical
      aspects of the underlying mechanism and its dependence on the NP morphology
      remain unclear. In this manuscript we characterize the apoptotic efficacy of
      nanoconjugated EGF as a function of NP size (with sphere diameters in the range
      20-80 nm), aspect ratio (A.R., in the range of 4.5 to 8.6), and EGF surface
      loading in EGFR overexpressing MDA-MB-468 cells. We demonstrate a significant
      size and morphology dependence in this relatively narrow parameter space with
      spherical NP with a diameter of approx. 80 nm being much more efficient in
      inducing apoptosis than smaller spherical NP or rod-shaped NP with comparable EGF
      loading. The nanoconjugated EGF is found to trigger an EGFR-dependent increase in
      cytoplasmic reactive oxygen species (ROS) levels but no indications of increased
      mitochondrial ROS levels or mitochondrial membrane damage are detected at early
      time points of the apoptosis induction. The increase in cytoplasmic ROS is
      accompanied by a perturbation of the intracellular glutathione homeostasis, which
      represents an important check-point for NP-EGF mediated apoptosis. Abrogation of
      the oxidative stress through the inhibition of EGFR signaling by the EGFR
      inhibitor AG1478 or addition of antioxidants N-acetyl cysteine (NAC) or tempol,
      but not trolox, successfully suppressed the apoptotic effect of nanoconjugated
      EGF. A model to account for the observed morphology dependence of EGF
      nanoconjugation enhanced apoptosis and the underlying NP-cell interactions is
      discussed.

PMID- 29589624
TI  - Engineering design toward exploring the functional group substitution in 1D
      channels of Zn-organic frameworks upon nitro explosives and antibiotics
      detection.
AB  - Three isostructural metal-organic frameworks denoted as Zn(L)(aip).(H2O) (1),
      Zn(L)(ip).(DMF)(H2O)1.5 (2), and Zn(L)(HBTC).(H2O)2 (3) with functional groups 
      NH2, -H and -COOH, respectively, decorated on the 1D channels have been
      rationally designed with the purpose of exploring the influence of electron
      transfer from organic ligands in the 1D channels on the sensing of nitro
      explosives and antibiotics. These three compounds exhibit strong fluorescence in
      water, and they can be applied to detect the presence of explosives or
      antibiotics by means of fluorescence quenching in aqueous solution, whereas in
      terms of special explosives or antibiotics at the same concentration, 3
      demonstrates a more superior quenching efficiency than 1 and 2. More importantly,
      it has been found that the difference in the sensing performances of these
      compounds is closely related to the interaction between the functional groups and
      guest molecules via electron and energy transfer from MOFs to explosives and
      antibiotics.

PMID- 29589626
TI  - Interplay between a crystal's shape and spatiotemporal dynamics in a spin
      transition material.
AB  - We investigated by means of optical microscopy (OM) the spatiotemporal features
      of the thermo-induced spin transition of [Fe(2-pytrz)2{Pd(CN)4}].3H2O (1) (2
      pytrz = 4-(2-pyridyl)-1,2,4,4H-triazole) single crystals having two different
      shapes (triangle and rectangle). While magnetic and calorimetric measurements,
      performed on a polycrystalline material, showed the respective average heating
      and cooling transition temperatures of (Tdown1/2 ~ 152 K, Tup1/2 ~ 154 K) and
      (Tdown1/2 ~ 160.0 K, Tup1/2 ~ 163.5 K), OM studies performed on a unique single
      crystal revealed significantly different switching temperatures (Tdown1/2 ~ 152 K
      and Tup1/2 ~ 162 K). OM investigations showed an interface spreading over all
      crystals during the spin transition. Thanks to the color contrast between the low
      spin (LS) and the high-spin (HS) states, we have been able to follow the real
      time dynamics of the spin transition between these two spin states, as well as
      access the thermal hysteresis loop of each single crystal. After image
      processing, the HS-LS interface's velocity was carefully estimated in the ranges
      [4.4-8.5] MUm s-1 and [2.5-5.5] MUm s-1 on cooling and heating, respectively. In
      addition, we found that the velocity of the interface is shape-dependent, and
      accelerates nearby the crystal's borders. Interestingly, we observed that during
      the propagation process, the interface optimizes its shape so as to minimize the
      excess of elastic energy arising from the lattice parameter misfit between the LS
      and HS phases. All of these original experimental results are well reproduced
      using a spatiotemporal model based on the description of the spin-crossover
      problem as a reaction diffusion phenomenon.

PMID- 29589625
TI  - Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced
      browning in a Ucp-1 reporter mouse model of obesity.
AB  - Browning in adipose tissues, which can be affected by diet, may mitigate the
      detrimental effects of adiposity and improve longer-term metabolic health. Here,
      browning-inducing effects of long-chain polyunsaturated fatty acids, e.g.,
      arachidonic acid (ARA)/docosahexaenoic acid (DHA) and extensively hydrolyzed
      casein (eHC) were investigated in uncoupling protein 1 (Ucp-1) reporter mice. To
      address the overall functionality, their potential role in supporting a healthy
      metabolic profile under obesogenic dietary challenges later in life was
      evaluated. At weaning Ucp1+/LUC reporter mice were fed a control low fat diet
      (LFD) with or without ARA + DHA, eHC or eHC + ARA + DHA for 8 weeks until week 12
      after which interventions continued for another 12 weeks under a high-fat diet
      (HFD) challenge. Serology (metabolic responses and inflammation) and in vivo and
      ex vivo luciferase activity were determined; in the meantime browning-related
      proteins UCP-1 and the genes peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha (PGC1alpha), PR domain containing 16 (PRDM16) and Ucp-1 were
      examined. ARA + DHA, eHC or their combination reduced body weight gain and
      adipose tissue weight compared to the HFD mice. The interventions induced Ucp-1
      expression in adipose tissues prior to and during the HFD exposure. Ucp-1
      induction was accompanied by higher PGC1a and PRDM16 expression. Glucose
      tolerance and insulin sensitivity were improved coinciding with lower serum
      cholesterol, triglycerides, free fatty acids, insulin, leptin, resistin,
      fibroblast growth factor 21, alanine aminotransferase, aspartate aminotransferase
      and higher adiponectin than the HFD group. HFD-associated increased systemic (IL
      1beta and TNF-alpha) and adipose tissue inflammation (F4/80, IL-1beta, TNF-alpha,
      IL-6) was reduced. Studies in a Ucp-1 reporter mouse model revealed that early
      intervention with ARA/DHA and eHC improves metabolic flexibility and attenuates
      obesity during HFD challenge later in life. Increased browning is suggested as,
      at least, part of the underlying mechanism.

PMID- 29589627
TI  - Preparation of an ultrathin Pt electrocatalyst via a galvanic replacement
      reaction of electrodeposited CuCl for the oxidation of methanol in an alkaline
      medium.
AB  - An ultrathin Pt electrocatalyst is prepared by the electrodeposition of a thin
      and uniform CuCl semiconductor film on an Au electrode followed by a galvanic
      replacement reaction with K2PtCl4, which shows an ultrahigh Pt-mass specific
      electrocatalytic activity of 23.7 mA MUgPt-1 for methanol oxidation in an
      alkaline medium.

PMID- 29589628
TI  - Variations and applications of the oxygen reduction reaction in ionic liquids.
AB  - Increasing energy demands call for new energy storage technologies with high
      energy density to meet current and future needs. Metal-air batteries are
      especially attractive due to their superior specific energy, which is as much as
      8 times that of today's best Li-ion batteries. However, the practical values
      achieved to date are far from the theoretical one and require further research to
      enhance the battery performance. The electrolyte plays an important role in the
      performance of the battery whose properties can be tuned by varying the chemical
      composition and through the use of additives. That is the case of ionic liquids
      which offer a wide variety of anion-cation combinations to realise maximum
      performance. This feature article overviews recent developments in ionic liquids
      as electrolytes for both magnesium-air and sodium-air batteries.

PMID- 29589630
TI  - Ionothermal synthesis of discrete supertetrahedral Tn (n = 4, 5) clusters with
      tunable components, band gaps, and fluorescence properties.
AB  - The preparation of crystalline molecularly supertetrahedral Tn clusters with
      variable sizes and components is of vital importance for the fundamental study of
      their physicochemical properties. However, setting up an efficient method to
      stabilize large discrete Tn clusters is a challenge due to their high negative
      charges and polymerization nature. In this work, we report on the ionothermal
      synthesis of three discrete T4 cluster compounds, namely
      [Bmmim]5[(CH3)2NH2]4[NH4][M4In16S31(SH)4].6H2O (M = Mn (1), Zn (2), Cd (3), Bmmim
      = 1-buty-2,3-dimethyl-imidazolium), and four discrete T5 cluster compounds,
      namely [Bmmim]10[NH4]3[Cu5Ga30-xInxS52(SH)4] (x = 6.6 (5), 14.5 (6), 23.8 (7),
      and 30 (8)). The compound [Bmmim]10[NH4]3[Cu5Ga30S52(SH)4] (4) previously
      reported by us features a discrete T5 cluster. The steep UV-Vis absorption edges
      indicate band gaps of 2.20 eV for 1, 2.64 eV for 2, 2.69 eV for 3, 3.04 eV for 4,
      2.65 eV for 5, 2.48 eV for 6, 2.32 eV for 7, and 2.30 eV for 8. The compositions
      of T5 clusters could be varied with the ratios of Ga : In in the starting
      reagents, providing an opportunity to systematically control the band gaps and
      fluorescence performances of T5 cluster-based compounds. This research might
      advance the understanding of the ionothermal preparation and functionality tuning
      of crystalline chalcogenides.

PMID- 29589629
TI  - Protective effects of Coptis chinensis inflorescence extract and linarin against
      carbon tetrachloride-induced damage in HepG2 cells through the MAPK/Keap1-Nrf2
      pathway.
AB  - Coptis chinensis inflorescence is traditionally used as tea and has been popular
      in the local market. C. chinensis inflorescence extract (CE) exhibits protective
      effects against carbon tetrachloride (CCl4)-induced damage, but the underlying
      mechanism remains unclear. The main chemicals of CE were detected, purified, and
      identified in this study. CE and linarin could reverse changes in cell viability,
      decrease alanine aminotransferase and aspartate transaminase levels, and reduce
      reactive oxygen species (ROS) generation induced by CCl4 in HepG2 cells. CE and
      linarin could also phosphorylate mitogen-activated protein kinases (MAPKs) and up
      regulate Kelth-like ECH-associated protein (Keap1). The pathways of MAPKs and
      Keap1 lead to the separation of Keap1 and nuclear factor (erythroid-derived 2)
      like 2 (Nrf2). Free Nrf2 transferred to the nucleus and enhanced the expression
      of phase II detoxification enzymes. This study provides a scientific basis for
      the use of C. chinensis inflorescence, which exhibits a hepatoprotective
      function, as a supplement in the food industry.

PMID- 29589632
TI  - Layered rare-earth hydroxide (LRH, R = Tb, Y) composites with fluorescein:
      delamination, tunable luminescence and application in chemosensoring for
      detecting Fe(iii) ions.
AB  - We demonstrate a novel example of tunable luminescence and the application of the
      delaminated FLN/OS-LRH composites (LRHs are layered rare-earth hydroxides, R =
      Tb, Y; FLN is the fluorescein named 2-(6-hydroxy-3-oxo-(3H)-xanthen-9-yl)benzoic
      acid; OS is the anionic surfactant 1-octane sulfonic acid sodium) in detecting
      Fe(iii) ions. The FLNxOS1-x species (x = 0.02, 0.05, 0.10, and 0.20) are
      intercalated into the LTbyY1-yH layers (y = 1, 0.9, 0.7, 0.5, 0.3, 0.1 and 0) by
      ion exchange reactions to yield the composites FLNxOS1-x-LTbyY1-yH. In the solid
      state, the LYH composites display green emission (564 nm) arising from the
      organic FLN, while in LTbH composites, the luminescence of the Tb3+ in the layers
      (545 nm) and the FLN in the interlayers is co-quenched. In the delaminated state
      in formamide (FM), FLNxOS1-x-LTbH composites display green to yellowish-green
      luminescence (540-574 nm) following the increasing FLN/OS ratio; while the
      FLN0.02OS0.98-LTbyY1-yH composites show green emission at ~540 nm. The
      fluorescence lifetimes of the composites (4.22-4.63 ns) are comparable to the
      free FLN-Na, and the quantum yields (31.62-78.70%) of the composites especially
      that (78.70%) of the FLN0.02OS0.98-LYH are much higher than that (28.40%) of free
      FLN-Na. The recognition ability of the FLN0.02OS0.98-LYH composite for metal
      cations is researched. The delaminated FLN0.02OS0.98-LYH colloidal suspension
      exhibits high selectivity for Fe3+ over other ions (Mg2+, Al3+, Ni2+, Co2+, Cu2+,
      Zn2+, Mn2+, Pb2+, and Cd2+) with fluorescence quenching, which can work as a kind
      of turn-off fluorescence sensor for the detection of Fe3+. The detection limit of
      Fe3+ is determined to be 2.58 * 10-8 M and the quenching constant (Ksv) is 1.70 *
      103 M-1. This is the first work on LRH materials working as a chemosensor for
      recognising metal cations. It provides a new approach for the design of LRH
      materials to be applied in fluorescence chemosensing.

PMID- 29589631
TI  - Broad bean (Vicia faba L.) pods: a rich source of bioactive ingredients with
      antimicrobial, antioxidant, enzyme inhibitory, anti-diabetic and health-promoting
      properties.
AB  - This study was aimed at investigating the chemical composition (proximate,
      minerals, fatty acids and phenolic compounds) and the in vitro (antimicrobial,
      radical scavenging, anti-acetylcholinesterase and protein denaturing activities)
      and in vivo (anti-diabetic and histo-protective effects in alloxan-induced
      diabetic mice) biological activities of broad bean pods (BBPs), a food waste by
      product material. The results showed that BBPs have high dietary fiber (57.46%),
      carbohydrate (18.93%) and protein (13.81%) content versus low fat content (<1%)
      contributing to a low energy value of 139.24 kcal per 100 g. Profiling of fatty
      acids showed an abundance of the essential polyunsaturated alpha-linolenic and
      linoleic acids, exhibiting an excellent nutritional quality as revealed by their
      low atherogenic and thrombogenic indices and their hypocholesterolemic
      properties. The methanol extract which exhibited the highest total phenolic,
      flavonoid and tannin contents was found to be the most active extract in terms of
      antimicrobial and anti-radical activities. In alloxan-induced diabetic mice, the
      oral administration of a methanol extract (500 mg per kg bw) attenuated the
      elevated levels of serum alanine aminotransferase (ALA), aspartate
      aminotransferase (AST), and alkaline phosphatase activities, and urea, uric acid,
      and creatinine. It effectively normalized the status of lipid profiles, mitigated
      oxidative stress through the activation of antioxidant enzymes (CAT, GPx and
      SOD), and alleviated oxidative stress-mediated histopathological changes in the
      pancreas, liver, kidney and testis. Compositional analysis by HPLC-PDA-ESI-MS/MS
      revealed the presence of flavan-3-ols (catechin, epicatechin and their
      derivatives), flavones (apigenin derivatives) and flavonols (glycosides of
      quercetin and kaempferol), among others. These findings suggest that BBPs may be
      an effective functional food for the management of diabetes and its
      complications.

PMID- 29589633
TI  - Synthesis and coordination chemistry of enantiopure t-BuMeP(O)H.
AB  - Both enantiomers of the optically pure Secondary Phosphine Oxide (SPO) t
      BuMeP(O)H (1) have been obtained by deboronation of phosphinous acid-borane t
      BuMeP(O)H.BH3 (3) with HBF4 followed by hydrolysis of the intermediate adduct t
      BuMeP(O)H.BF3 (1.BF3), which has been isolated and crystallographically
      characterised. Complexes [MCl(COD)(kappaP-(R)-1)] (M = Ir, Rh; 4 and 7
      respectively) have been detected in solution but could not be isolated while
      trans-[RhCl(CO)(kappaP-(S)-1)2] (9) has been successfully obtained in good yield.
      Gold complex [AuCl(kappaP-(S)-1)] (10) has been prepared and its crystal
      structure shows the presence of aurophilic interactions. Three new ruthenium
      complexes ([RuCl2(eta6-p-cymene)(kappaP-(R)-1)], 12), ([RuCl2(CO)3(kappaO-(S)
      1)], 13) and trans-([RuCl2(CO)2(kappaP-(S)-1)2], 14) have been synthesised and
      fully characterised, including the crystal structure of 12. Four palladium
      coordination compounds have been prepared: trans-[PdCl2(kappaP-(S)-1)2] (trans
      15), [Pd(MU-Cl)(kappaP-(S)-1)2]2 (16.OH and 16.BF2) and [Pd(MU-OAc)(kappaP-(S)
      1)2] (17) and the crystal structure of complex 16.OH proves the pseudobidentate
      coordination of the two molecules of 1. Three organometallic allylpalladium
      complexes have been prepared namely [Pd(eta3-Ph2C2H3)Cl(kappaP-(S)-1)] (18) and
      [Pd(eta3-Ph2C2H3)(kappaP-(S)-1)2] (19.OH and 19.BF2). The crystal structure of
      19.BF2 constitutes the first allylpalladium-SPO complex reported to date.

PMID- 29589634
TI  - Microporous carbons derived from organosilica-containing carbon dots with
      outstanding supercapacitance.
AB  - In this study, a series of strongly luminescent organosilica-modified carbon dots
      were successfully synthesized in a scalable manner via hydrothermal treatment of
      citric acid and glucose in the presence of a silane coupling agent. Organosilica
      as a stable component coupled with the surface of carbons leads to the formation
      of gel-like materials. The obtained carbon dots can be homogeneously dispersed in
      various polar solvents such as water or ethanol to produce an optical solution.
      Importantly, the abundance of organosilica groups on the surface makes carbon
      dots ideally suited for use as fantastic carbon precursors for the construction
      of porous carbon materials. The carbons resulting from the pyrolysis of carbon
      dots consist of interconnected carbon nanoparticles with surface areas of up to
      725 m2 g-1 and nitrogen content of 4.84%. Such carbons show potential application
      as supercapacitor electrodes with high specific capacitance of 185.4 F g-1 at 0.5
      A g-1 and 176.3 F g-1 at 1 A g-1 in 6 mol L-1 KOH. Considered a relatively green
      and simplistic process, this current synthetic protocol would be a promising
      avenue to access functional carbon materials with tunable porosity, heteroatom
      doping and specific morphology.

PMID- 29589635
TI  - Electrochemical properties of reduced graphene oxide derived through camphor
      assisted combustion of graphite oxide.
AB  - A facile method was demonstrated for the one-step synthesis of reduced graphene
      oxide (rGO) from graphite oxide (GO) using a camphor assisted combustion (CAC)
      process. Analysis of samples was carried out using FT-IR, XRD, TGA, Raman, BET,
      SEM and TEM techniques. The electrochemical properties of the rGO samples derived
      through the CAC process were determined using cyclic voltammetry, galvanostatic
      charge/discharge and impedance spectroscopy. It has been observed that the
      specific surface area and porosity of the rGO samples decrease with the
      increasing concentration of camphor during the CAC synthesis process. Thus,
      different mass ratios of GO and camphor such as 1 : 12, 1 : 16, and 1 : 20 in the
      CAC process yield rGO samples having surface areas (SBET) of 313.3, 297.5 and
      177.4 m2 g-1. The pore volumes of the respective samples are 0.44, 0.45 and 0.23
      cm3 g-1, respectively. The rGO derived using the 1 : 12 mass ratio of GO and
      camphor (rGO-12C) exhibits a high specific capacitance of 241 F g-1, which is
      significantly higher than that observed for chemically reduced graphene oxide
      (rGO-CR), which exhibits a specific capacitance value of only 153 F g-1. The
      capacitance retention of rGO-12C was found to be 98% even after 1000
      galvanostatic charge-discharge (GCD) cycles, suggesting its potential
      applications in electrochemical energy storage.

PMID- 29589636
TI  - Supplementation of vitamin D after birth affects body size and BMI in Polish
      children during the first 3.5 years of life - an analysis based on two cohorts
      measured in the years 1993-1997 and 2004-2008.
AB  - ABSTRACT: Objectives: The aim of this study was to assess whether the time of
      vitamin D supplementation after birth, season of birth and the type of feeding
      affected current body weight, body height and BMI among children aged 3-56 months
      from two cohorts. Additionally, it was analysed whether birth weight and birth
      length correlated with current BMI, body height and body weight in both cohorts
      of children. Methods: The study material included 1930 children from the two
      cohorts, measured in two following periods: 1993-1997 and 2004-2008. Finally 849
      healthy individuals aged 3-56 months were included in the analysis. Multiple
      stepwise regression model was applied to find the group of the most important
      variables explaining current body weight, body height and BMI. Moreover
      generalized linear models for two way interactions were used. Results: The season
      of birth, time of supplementation of vitamin D, but also birth weight and length
      might affect current body weight. Individuals' height could be associated with
      birth length and the season of birth. BMI value was probably regulated by birth
      length and weight. Furthermore, interactions between the time of vitamin D
      supplementation and season of birth and also between the time of vitamin D
      supplementation and type of feeding resulting in variation of body weight and BMI
      in the first years of life were also observed. Conclusions: The study underlines
      the importance of a supplementation of vitamin D, season of birth and birth
      weight and length in current weight, height and body proportion in the first 3.5
      years of life.

PMID- 29589637
TI  - Trends in the epidemiology of erysipelas in Slovenia.
AB  - INTRODUCTION: Erysipelas is a common infection of the skin and subcutaneous
      tissue. Despite the relative frequency of erysipelas, data on its basic
      epidemiological characteristics are scant. This study describes the trends in
      erysipelas epidemiology in Slovenia. METHODS: Data on notified erysipelas cases
      from 2000 to 2016 were extracted from the electronic database of reportable
      communicable diseases and analyzed. RESULTS: There were 36,254 notified cases
      during the observed time period of 17 years. The yearly age-standardized
      incidence rate of erysipelas increased from 71.5 per 100,000 in 2000 to 111.3 per
      100,000 in 2016, with the main rise in the >= 75 age group. Erysipelas was more
      common in women, but the sex-related difference lessened in the period observed.
      The hospitalization rate declined. Erysipelas was significantly more frequent in
      the warmer period of the year. The correlation between erysipelas incidence and
      average monthly temperature was stronger in the <= 64 age group than in the >= 65
      age group. CONCLUSIONS: Retrospective observational data confirmed a rising trend
      in erysipelas cases, especially among the elderly. Aging of the population will
      continue to increase the burden of the disease, unless health promotion and
      prevention lowers the prevalence of the risk factors.

PMID- 29589638
TI  - Psoriasis and comorbidities: general practitioners' awareness.
AB  - INTRODUCTION: Systemic inflammatory diseases such as psoriasis, systemic lupus
      erythematosus (SLE), and rheumatoid arthritis (RA) are associated with an
      increased prevalence of cardiovascular diseases (CVD) and other comorbidities.
      The primary aim of this study was to assess the screening practices of general
      practitioners (GPs) with regard to the most frequent comorbidities in patients
      with psoriasis. METHODS: We adapted, with permission, a questionnaire that was
      used by Parsi et al. in 2012, which was then distributed to GP residents and
      consultants. RESULTS: Overall, 372 questionnaires were collected. Significantly
      more physicians screen for CV risk factors in patients with RA and SLE than in
      patients with psoriasis. There was no statistically significant difference
      between GP residents in the initial and final phase of residency, or between GP
      residents and consultants regarding awareness of increased prevalence of CVD in
      psoriasis or comorbidity screening practices in psoriasis patients. CONCLUSIONS:
      Most GP residents and consultants that participated in this study are not aware
      of an increased CV risk in patients with psoriasis and assign greater importance
      regarding this risk to other inflammatory diseases such as RA and SLE.

PMID- 29589639
TI  - Oral manifestations of autoinflammatory and autoimmune diseases.
AB  - Autoimmune diseases may also be reflected in changes in the oral cavity that
      represent the first sign of the disease, or they may occur simultaneously with or
      later in the course of the disease. Oral findings are mostly non-specific, and
      therefore further investigations are needed to exclude or confirm possible
      diagnoses. This article presents the most important diseases in this research
      area, divides them into meaningful groups, and highlights the importance of
      examining the oral cavity for possible manifestations.

PMID- 29589640
TI  - The role of regulatory T cells and anti-inflammatory cytokines in psoriasis.
AB  - Psoriasis is a chronic inflammatory disease with a genetic predisposition that
      can be triggered by environmental factors. Pathogenesis is characterized by
      activation of the Th1/Th2 axis and abnormalities of the Th17/Treg balance as well
      as deficiency of anti-inflammatory cytokines (IL-10, TGF-beta). Regulatory
      lymphocytes (Treg), which are involved in homeostasis mechanisms, maintain
      tolerance and prevent autoimmune disorders. Only a few studies have investigated
      the presence of Treg marker expression and levels of anti-inflammatory cytokines
      in psoriatic skin and sera of patients with psoriasis. The results of studies are
      controversial. This article reviews and analyzes what is known about the role of
      Treg cells and anti-inflammatory cytokines in psoriasis.

PMID- 29589641
TI  - Cutaneous squamous cell carcinoma complicating hidradenitis suppurativa: a review
      of the prevalence, pathogenesis, and treatment of this dreaded complication.
AB  - Hidradenitis suppurativa (HS) is a chronic and debilitating skin disorder
      characterized by the formation of painful abscesses, draining sinus tracts, and
      scarring, predominantly in skin folds such as the axillae and the perineum. The
      exact prevalence of HS is unknown because the disease is often underreported, but
      it has been estimated to be as high as 4.1%. HS is three times more prevalent in
      women than in men. Various comorbidities have been associated with HS, including
      inflammatory bowel disease and squamous cell carcinoma (SCC). The transformation
      of chronic HS to SCC is often considered the most severe complication of HS. The
      prevalence of SCC associated with HS is approximately 4.6%, and is more common
      among men. It is likely that the chronic irritation and inflammation
      characteristic of HS drive the malignant transformation to SCC, and recent work
      has identified other potential risk factors for this malignant transformation,
      including human papillomavirus (HPV) infection and tobacco use. Treatment
      modalities have expanded in recent years to include triple antibiotic therapy,
      immunomodulatory biologic agents, laser therapy, and surgical excision. Knowledge
      of these comorbid associations of HS, especially the malignant transformation to
      SCC, is highly important for the management and follow-up of this chronic
      disease.

PMID- 29589642
TI  - Inflamed bilateral linear atrophoderma of Moulin in an adult woman: a case
      report.
AB  - Linear atrophoderma of Moulin (LAM) is a rare dermatosis characterized by a
      hyperpigmented atrophoderma that follows Blaschko's lines, with onset usually
      occurring during childhood and adolescence. LAM is an etiologically unknown form
      of dermal atrophy. It is generally characterized by oval or round atrophic,
      nonsclerotic, hyperpigmented patches following Blaschko's lines. These patches
      are usually located on the trunk and the upper and lower extremities. This case
      study discusses a patient that had the nonclassical form of LAM with the initial
      lesions presenting as papules.

PMID- 29589643
TI  - A rare and isolated presentation of primary cutaneous anaplastic large cell
      lymphoma.
AB  - Primary cutaneous anaplastic large cell lymphoma is a CD30+ lymphoproliferative
      disorder of the skin characterized by the absence of nodal and visceral
      involvement, low recurrence rate, spontaneous remission, and tendency to occur in
      patients older than 20 years. The case presented here is of a 15-year-old boy
      with grouped papular lesions arranged in an annular fashion with a central
      clearing on his right arm for 4 months that was diagnosed with a case of
      anaplastic lymphoma kinase-negative primary cutaneous CD30+ anaplastic large cell
      lymphoma. The CT scan, bone marrow biopsy, and laboratory data ruled out systemic
      involvement. He was treated with oral methotrexate 10 mg once a week, but was
      lost to follow-up.

PMID- 29589644
TI  - Congenital atrichia with papular lesions: a rare cause of irreversible childhood
      alopecia.
AB  - Congenital atrichia with papular lesions (APL) is a disease characterized by the
      complete absence of hair from the whole body occurring within a few months of
      birth and the presence of papules distributed over the body. A 9-year-old boy
      presented with sparse hair over his body and with a history of losing his hair
      soon after birth. Multiple skin-colored papules were observed over the scalp. A
      biopsy from a papule showed keratinous cysts in the dermis and the absence of
      hair follicles. A diagnosis of congenital APL was made after vitamin D-dependent
      rickets was excluded. This case highlights congenital APL as a cause of total
      alopecia.

PMID- 29589645
TI  - Chronic peripheral edema in a patient with rheumatoid arthritis.
AB  - Chronic peripheral edema is a very common yet underestimated problem. It is of
      utmost importance to investigate various possible causes and understand the
      pathophysiological mechanisms of chronic peripheral edema in order to determine
      the optimal treatment. This case report presents the case of a polymorbid patient
      with a deformity-causing type of rheumatoid arthritis and a 1-year history of
      progressive symmetrical peripheral edema. Based on an extensive diagnostic
      investigation, the patient was diagnosed with a combined form of chronic
      peripheral edema comprised of true lymphedema, which was confirmed by
      lymphoscintigraphy, and filtration edema due to muscular inactivity. Edema as a
      side effect of tocilizumab was also suspected.

PMID- 29589646
TI  - Fat and MEAT. A rare benign lesion of adipose tissue.
AB  - The concept of mobile tumors was introduced by Shelley and Shelley in 2006. They
      coined the term abacus tumor. Mobile lipomas have been described in the
      literature as an example of abacus tumors. This was later questioned by Burgdorf
      et al., who performed comparative studies in cattle. They suggested the term
      mobile encapsulated adipose tissue (MEAT) for lipoma-like mobile lesions in
      cattle and people. We report two more cases of MEAT in adult patients and discuss
      the literature on this unusual subject.

PMID- 29589647
TI  - Primary systemic amyloidosis with skin and cardiac involvement: a case report
AB  - Primary systemic amyloidosis is characterized by the deposition of insoluble
      monoclonal immunoglobulin light chains in various tissues and is usually
      associated with an underlying plasma cell dyscrasia. In the early stage of the
      disease, dermatological findings can be the only manifestation, as opposed to
      organ involvement in the later stages. A dermatologist can diagnose amyloidosis
      early with a skin biopsy stained with Congo red dye and other appropriate
      investigations. This case report describes a female patient with primary systemic
      amyloidosis confirmed histologically from a skin biopsy. When the diagnosis was
      established, cardiac involvement and monoclonal gammopathy were already present.
      Treatment with bortezomib and dexamethasone was initiated; due to side effects,
      the treatment was later switched to lenalidomide, which was better tolerated.

PMID- 29589648
TI  - Alopecia areata and salmon patch: an actual association?

PMID- 29589649
TI  - Bone formation by heterodimers through non-viral gene delivery of BMP-2/6 and BMP
      2/7.
AB  - Non-viral gene delivery is a safe technique to release sustained physiologic
      dosages of bone morphogenetic protein (BMP). Co-delivery of multiple BMPs can
      result in the formation of more potent BMP heterodimers. In this study, non-viral
      co-delivery of BMP-2/6 and BMP-2/7, as a mean to produce heterodimers, was
      assessed. Goat MSCs were non-virally transfected with plasmid DNA encoding BMP
      isoforms (pBMP) known to be relevant for osteogenesis: BMP-2, -6 or -7. As a
      result, BMP-2, -6 and -7 were produced and detectable for up to 14 d and their
      combined delivery (pBMP-2 with pBMP-6 or pBMP-7) was used to create BMP-2/6 and
      BM-2/7 heterodimers. Formation and secretion of the heterodimer proteins was
      validated by sandwich enzyme-linked immunosorbent assay (ELISA). Produced BMPs
      and heterodimers were biologically active, as confirmed by differentiation of
      reporter cells and MSCs. To assess bone formation, transfected MSCs were seeded
      on to ceramic scaffolds and implanted subcutaneously into nude mice. Bone
      formation was significantly enhanced in the pBMP-2/6 condition and a trend for
      more bone formation was observed in the pBMP-2/7 and pBMP-6 homodimer condition.
      No bone was found in the pBMP-2, pBMP-7 or control condition. In conclusion,
      simultaneous delivery of pBMP-2 with pBMP-6 or -7 resulted in the production of
      heterodimers that were beneficial for bone formation as compared to BMP
      homodimers. Combination of BMP sequences could reduce the need for high BMP
      protein dosages and might enhance prolonged availability of the growth factors.

PMID- 29589651
TI  - ?

PMID- 29589650
TI  - Relaxation techniques for pain management in labour.
AB  - BACKGROUND: Many women would like to avoid pharmacological or invasive methods of
      pain management in labour and this may contribute to the popularity of
      complementary methods of pain management. This review examined currently
      available evidence on the use of relaxation therapies for pain management in
      labour. This is an update of a review first published in 2011. OBJECTIVES: To
      examine the effects of mind-body relaxation techniques for pain management in
      labour on maternal and neonatal well-being during and after labour. SEARCH
      METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (9 May
      2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 5 2017), MEDLINE (1966 to 24 May 2017), CINAHL (1980 to 24 May
      2017), the Australian New Zealand Clinical Trials Registry (18 May 2017),
      ClinicalTrials.gov (18 May 2017), the ISRCTN Register (18 May 2017), the WHO
      International Clinical Trials Registry Platform (ICTRP) (18 May 2017), and
      reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled
      trials (including quasi randomised and cluster trials) comparing relaxation
      methods with standard care, no treatment, other non-pharmacological forms of pain
      management in labour or placebo. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and risk of bias, extracted data and
      checked them for accuracy. We attempted to contact study authors for additional
      information. We assessed evidence quality with GRADE methodology. MAIN RESULTS:
      This review update includes 19 studies (2519 women), 15 of which (1731 women)
      contribute data. Interventions examined included relaxation, yoga, music and
      mindfulness. Approximately half of the studies had a low risk of bias for random
      sequence generation and attrition bias. The majority of studies had a high risk
      of bias for performance and detection bias, and unclear risk of bias for,
      allocation concealment, reporting bias and other bias. We assessed the evidence
      from these studies as ranging from low to very low quality, and therefore the
      effects below should be interpreted with caution.RelaxationWe found that
      relaxation compared to usual care provided lowered the intensity of pain
      (measured on a scale of 0 to 10 with low scores indicating less pain) during the
      latent phase of labour (mean difference (MD) -1.25, 95% confidence interval (CI) 
      1.97 to -0.53, one trial, 40 women). Four trials reported pain intensity in the
      active phase; there was high heterogeneity between trials and very low-quality
      evidence suggested that there was no strong evidence that the effects were any
      different between groups for this outcome (MD -1.08, 95% CI -2.57 to 0.41, four
      trials, 271 women, random-effects analysis). Very low-quality evidence showed
      that women receiving relaxation reported greater satisfaction with pain relief
      during labour (risk ratio (RR) 8.00, 95% CI 1.10 to 58.19, one trial, 40 women),
      and showed no clear benefit for satisfaction with childbirth experience (assessed
      using different scales) (standard mean difference (SMD) -0.03, 95% CI -0.37 to
      0.31, three trials, 1176 women). For safety outcomes there was very low-quality
      evidence of no clear reduction in assisted vaginal birth (average RR 0.61, 95% CI
      0.20 to 1.84, four trials, 1122 women) or in caesarean section rates (average RR
      0.73, 95% CI 0.26 to 2.01, four trials, 1122 women). Sense of control in labour,
      and breastfeeding were not reported under this comparison.YogaWhen comparing yoga
      to control interventions there was low-quality evidence that yoga lowered pain
      intensity (measured on a scale of 0 to 10) with low scores indicating less pain)
      (MD -6.12, 95% CI -11.77 to -0.47, one trial, 66 women), greater satisfaction
      with pain relief (MD 7.88, 95% CI 1.51 to 14.25, one trial, 66 women) and greater
      satisfaction with childbirth experience (MD 6.34, 95% CI 0.26 to 12.42 one trial,
      66 women (assessed using the Maternal Comfort Scale with higher score indicating
      greater comfort). Sense of control in labour, breastfeeding, assisted vaginal
      birth, and caesarean section were not reported under this comparison.MusicWhen
      comparing music to control interventions there was evidence of lower pain
      intensity in the latent phase for women receiving music (measured on a scale of 0
      to 10 with low scores indicating less pain) (MD -0.73, 95% CI -1.01 to -0.45,
      random-effects analysis, two trials, 192 women) and very low-quality evidence of
      no clear benefit in the active phase (MD -0.51, 95% CI -1.10 to 0.07, three
      trials, 217 women). Very low-quality evidence suggested no clear benefit in terms
      of reducing assisted vaginal birth (RR 0.41, 95% CI 0.08 to 2.05, one trial, 156
      women) or caesarean section rate (RR 0.78, 95% CI 0.36 to 1.70, two trials, 216
      women). Satisfaction with pain relief, sense of control in labour, satisfaction
      with childbirth experience, and breastfeeding were not reported under this
      comparison.Audio analgesiaOne trial evaluating audio analgesia versus control
      only reported one outcome and showed no evidence of benefit in satisfaction with
      pain relief.MindfulnessOne trial evaluating mindfulness versus usual care found
      an increase in sense of control for the mindfulness group (using the Childbirth
      Self-Efficacy Inventory) (MD 31.30, 95% CI 1.61 to 60.99, 26 women). There is no
      strong evidence that the effects were any different between groups for
      satisfaction in childbirth, or for caesarean section rate, need for assisted
      vaginal delivery or need for pharmacological pain relief. No other outcomes were
      reported in this trial. AUTHORS' CONCLUSIONS: Relaxation, yoga and music may have
      a role with reducing pain, and increasing satisfaction with pain relief, although
      the quality of evidence varies between very low to low. There was insufficient
      evidence for the role of mindfulness and audio-analgesia. The majority of trials
      did not report on the safety of the interventions. Further randomised controlled
      trials of relaxation modalities for pain management in labour are needed. Trials
      should be adequately powered and include clinically relevant outcomes such as
      those described in this review.

PMID- 29589652
TI  - [When hair starts to fall out].
AB  - Hair loss causes physical and psychological distress and represents a common
      motive of consultation both in general practice and dermatology. Causes of hair
      loss are highly diverse and can lead to a challenging diagnosis, which can delay
      its management. Knowledge of the main causes and their different mechanisms are
      thus necessary in order to optimize both the diagnosis and treatment. The purpose
      of this paper is to describe the main causes of hair loss in order to improve its
      diagnosis and management.

PMID- 29589653
TI  - [Repurposing of betablockers in dermatology].
AB  - Betablockers are used for decades in the treatment of cardiovascular diseases.
      Recently, the repurposing of the wide spectrum betablocker propranolol
      revolutionized the infantile hemangioma management. Besides, betablockers have
      been shown to significantly improve the prognosis of melanoma patients. Blocking
      the adrenergic receptors blocks the stress-induced tumorigenic pathways.
      Propranolol inhibits melanoma by downregulating the tumor angiogenesis but also
      tumor cell proliferation, invasiveness and local immune suppression. These
      antitumor effects have been observed in other cancers. The repurposing of
      propranolol has already changed the practice of pediatricians and dermatologists
      and may soon help oncologists treat various cancers.

PMID- 29589654
TI  - [Nail alterations in children].
AB  - Alterations of the nail unit in children may be congenital or acquired, may be an
      isolated finding or part of a systemic problem or a syndrome. In this article we
      describe the most common childhood nail changes and underscore some important
      clinical clues that should motivate further investigations. Moreover we give a
      brief overview of the management of these nail pathologies.

PMID- 29589655
TI  - [Emerging systemic treatments of atopic dermatitis].
AB  - Atopic dermatitis (AD) is the most common inflammatory dermatitis for which
      molecular research is currently extending. Mostly mediated by helper T
      lymphocytes type 2 (Th2), it seems that Th22 and Th17 can also be involved on a
      smaller scale. An IL-4/IL-13 inhibitor, key cytokines of the Th2 pathway, has
      recently been recognized as a new treatment for AD and has opened the field to
      multiple clinical trials for other selective immunosuppressants such as biologics
      and small molecules. These advances make us hope for the development of more
      effective and better-tolerated treatments than conventional immunosuppressants.
      In addition, they promise to advance the knowledge of this complex inflammatory
      pathology and its clinical subtypes.

PMID- 29589656
TI  - [What's new in the management of atopic dermatitis in children and adolescents ?]
AB  - A better understanding of the atopic dermatitis (AD) pathogenesis and the need
      for more efficient and safer treatments in severe AD promoted the development of
      new therapies. Several underwent and are still undergoing clinical trials, but
      due to safety reasons, they include mainly adults for now. AD is however
      predominant in childhood with a prevalence 20 % in children compared to only 5 %
      in adults. Regarding the pediatric population, the new pipeline relies on two
      selective immunosuppressive agents, notably crisaborole (phosphodiesterase-4
      inhibitor) and dupilumab (IL-4 and IL-13 inhibitor). In order to strengthen the
      medical treatment, therapeutic patient education plays a supportive role in the
      global approach, allowing an optimized care. The Lausanne model of the Pediatric
      Dermatology Unit is described in this article.

PMID- 29589657
TI  - [Extracorporeal photopheresis].
AB  - During the treatment of extracorporeal photopheresis (ECP), white blood cells are
      collected by apheresis and exposed to ultraviolet A after incubation with 8
      methoxypsoralen. Although ECP was first developed for cutaneous T cell lymphoma,
      it has shown promising efficacy in a number of other serious conditions, like
      acute and chronic graft-versus-host disease, lung and cardiac transplant
      rejection and other autoimmune diseases. The ECP has been used for thirty years
      in some specialized centers but remains unknown to most of the physicians. The
      aim of this article is to review the practical aspects, the mode of action and
      the current indications of ECP.

PMID- 29589659
TI  - ?

PMID- 29589660
TI  - ?

PMID- 29589658
TI  - [Cardiology update 2017].
AB  - As usual, numerous papers published in 2017 contributed to optimize the
      management of patients in all clinical cardiologic fields. It is of course
      impossible to summarize them all in such an article. Subjects and papers were
      thus selected if they were thought to be particularly important for non
      cardiologist physicians, especially general practitioners. The authors would also
      like to take the opportunity of this article to honor the memory of Pr Daniel
      Wagner who unfortunately passed away after less than six months at the head of
      our Cardiology Department. He was well recognized for his generosity as well as
      his clinical and scientific competence. This article is dedicated to him.

PMID- 29589661
TI  - ?

PMID- 29589662
TI  - ?

PMID- 29589663
TI  - ?

PMID- 29589665
TI  - ?

PMID- 29589664
TI  - ?

PMID- 29589666
TI  - Erosion-protecting effect of oral-care products available on the Swiss market. A
      pilot study
AB  - The present study sought to test oral-care products available on the Swiss
      market, such as toothpastes and gels, with respect to the protection of enamel
      against erosive tooth wear. A total of 56 enamel specimens were divided into 7
      groups (n = 8): F-TP = Migros Budget Anti-Caries Toothpaste (Negative Control);
      F+Sn3500-TP = Elmex Erosion Protection Toothpaste (Positive Control); F-TP +
      F+Oligopep-Gel = Migros Budget Anti-Caries Toothpaste + Emofluor Protect Gel
      Professional; F+Sn3120-Gel = Emofluor Gel Intensive Care; F+Oligopep-TP = Candida
      Protect Professional Toothpaste; F+Sn1260-TP = Emoform-F Protect Toothpaste; and
      F+Sn3440-TP = Sensodyne Repair & Protect Toothpaste. The specimens were incubated
      in artificial saliva for 30 min and then brushed in a toothbrushing machine (10 s
      brushing; total 2 min exposure to the product). After the toothbrush abrasion,
      the specimens were rinsed, dried and submitted to an erosive challenge (2 min; 1%
      citric acid; pH 3.6). This sequence was repeated 4 times, and the total enamel
      surface loss was calculated using indentation measurements before and after the
      brushing period. All groups presented progressive surface loss throughout the
      experiment; after 4 cycles, total surface loss values ranged from 0.11 um
      (F+Sn3120-Gel) to 0.89 um (F+Sn1260-TP). Regarding the total surface loss values
      (median; interquartile range), F-TP (0.54; 0.42-0.59) presented no significant
      differences compared to any of the other groups. F+Sn3500-TP (0.33; 0.30-0.40), F
      TP + F+Oligopep-Gel (0.34; 0.29-0.42) and F+Sn3120-Gel (0.11; 0.09-0.15)
      presented lower surface loss than F+Oligopep-TP (0.75; 0.59-0.98), F+Sn1260-TP
      (0.89; 0.68-1.13) and F+Sn3440-TP (0.69; 0.66-0.78). Conclusion: Although some of
      the oral-care products containing stannous ions or oligopeptide-104 presented
      numerically lower SL values, they did not present significantly better protection
      than a regular fluoride toothpaste. The gels showed a general trend of better
      enamel protection against ETW.

PMID- 29589667
TI  - An analysis of effective dose optimization and its impact on image quality and
      diagnostic efficacy relating to dental cone beam computed tomography (CBCT)
AB  - The potential of high resolution, three-dimensional (3D) images which overcome
      limitations such as superimposition and anatomical noise of two-dimensional (2D)
      conventional imaging, has made cone beam computed tomography (CBCT) an
      increasingly popular imaging modality in many dental applications. It is in light
      of the increasingly prevalent use of CBCT, particularly in a primary dental care
      setting, that the goal of this review is to investigate what evidence-based
      guidance is available to the clinician to justify and reduce radiation risk of
      this higher dose imaging modality while maintaining diagnostically acceptable
      images. To this end, the literature on radiation dose and related patient risk
      was comprehensively investigated, before an analysis of the ways in which dose
      can be optimized and the implications that optimization has on image quality was
      discussed. Finally, although it is accepted that CBCT has the potential to
      improve diagnosis, it is uncertain if its use has positive ramifications on
      issues of diagnostic efficacy, including clinical decision-making and patient
      outcome. In order to investigate these issues, the levels of evidence of the
      existing studies and their validity were assessed. On review of the available
      literature, it is evident that there is limited practical advice available to
      dentists regarding dose optimization and any existing protocols may not be
      readily transferable to every CBCT machine, the manufacturers' role is not often
      conducive to dose limitation and that the bulk of evidence is at lower levels of
      evidence. Furthermore, there is minimal supporting evidence to suggest an impact
      of CBCT on diagnostic thinking and consequent choice of treatment and no evidence
      of a positive effect of CBCT on patient outcome.

PMID- 29589668
TI  - Percutaneous tricuspid valve replacement: orthotopic and heterotopic valves.
AB  - The tricuspid valve has long been described as the "forgotten valve", leaving
      tricuspid valve disease relatively neglected. However, the number of people in
      the United States affected by severe tricuspid regurgitation is growing. Isolated
      surgery for severe tricuspid regurgitation in the setting of right ventricular
      heart failure carries a high mortality risk, and therefore, attention to
      corrective therapies has increased. Because of the different etiologies for
      tricuspid regurgitation, multiple percutaneous transcatheter options for
      tricuspid valve repair for severe regurgitation are being studied and have been
      developed, including annuloplasty systems, leaflet and coaptation devices, vena
      caval (heterotopic) valve implantations, and tricuspid valve (orthotopic)
      replacement. In this paper, we review the heterotopic and orthotopic tricuspid
      valve transcatheter options for severe tricuspid regurgitation.

PMID- 29589669
TI  - Percutaneous coronary intervention risk scores.
AB  - Percutaneous coronary interventions in patients at high clinical risk with
      anatomical complexity is one of the most important topics in interventional
      cardiology. The development of materials and techniques allowed the
      interventional cardiologist to be able to treat virtually any coronary lesion.
      The patient's evaluation with clinical and anatomic risk scores allow the
      physicians to choose the best therapeutic strategy for each individual patient.

PMID- 29589670
TI  - Standardization of Impella(r)-assisted patient management.
AB  - The presence of high-risk features on candidates to percutaneous
      revascularization is increasingly leading to Impella(r)-assisted procedures
      (IAPs). While IAPs are safe and effective procedures, they still require managing
      a degree of complexity. Clinicians often rely on their ability to recall every
      step of operative procedures. However, during stressful situations, levels of
      cognitive function are compromised leading to planning and execution failures and
      decreased safety. Many high-risk activities such as aviation, aerospace industry,
      and nuclear plants have been using protocols, standardized procedures and
      checklists for many years. The purpose of the present article is to make a
      proposal for the standardization of ordinary medical activities required outside
      the Cath Lab for the management of patients before and after IAPs.

PMID- 29589671
TI  - Tricuspid valve regurgitation: epidemiology and pathophysiology.
AB  - Compared with the vast literature concerning the prevalence, pathophysiology, and
      outcome of left valvular disease, the data concerning tricuspid regurgitation
      (TR) is very limited. In this review we summarized the present data concerning
      these important issues. We show that TR is as prevalent as aortic stenosis in the
      community, with increasing prevalence with age, and much more common in women. We
      review the present knowledge concerning the pathogenesis of TR, focusing on
      functional TR. We show that functional TR is multifactorial, resulting from both
      RV remodeling and pulmonary hypertension, and/or atrial fibrillation resulting in
      right atrial dilatation. We demonstrate that RV remodeling, mostly in the mid
      segment, will result in tethering. On the other side, right atrial remodeling
      will mostly result in pure annular dilatation and loss of valvular/annular
      coverage reserve. Finally, due to the heterogeneous nature of TR we review the
      outcome data for each presentation of TR and show that in most contexts TR is
      associated with very poor outcome, even when adjusted for left ventricular
      systolic, and diastolic function, pulmonary pressure, and RV dysfunction.

PMID- 29589672
TI  - The Synergy stent in high-bleeding risk patients: why design matters.
AB  - Antithrombotic management after percutaneous coronary intervention is based on
      dual antiplatelet therapy (DAPT), that has unequivocally shown to reduce the risk
      of recurrent ischemic events at cost of an important risk of bleeding. In order
      to balance ischemic and bleeding risks, DAPT duration should be based on patients
      and lesions features as well as stent type. Based on these considerations,
      patients at high bleeding risk (HBR) undergoing PCI represent a challenging
      subgroup. The Synergy stent (Boston Scientific, Marlborough, MA, USA) is a new
      generation everolimus-eluting stent with a biodegradable polymer coating,
      presenting several features that have the potential to reduce acute and long-term
      thrombogenicity and the subsequent need for DAPT. The aim of this manuscript is
      to review the evidence about the impact of stent design on the optimal
      antithrombotic strategy in HBR patients and the potential role of the Synergy BP
      EES in this relevant population.

PMID- 29589673
TI  - Cardiac rehabilitation after STEMI.
AB  - Cardiac rehabilitation is the most important evidence-based intervention for
      secondary prevention after STEMI, nevertheless, only a minority of patients may
      access to a cardiac rehabilitation program. In this review the priority criteria
      for admission to cardiac rehabilitation and the main barriers that limit a larger
      involvement of the patients are discussed. Among the components of cardiac
      rehabilitation exercise is crucial and a tailored exercise training program and a
      tight monitoring of adherence to lifestyle recommendations are mandatory.
      Finally, the development of light cardiac rehabilitation pathways and home
      programs may allow a larger diffusion of outpatient programs. In conclusion, the
      participation to a cardiac rehabilitation program following STEMI is about 25-35%
      in western countries, and only 15% in Italy. Stressing the importance of cardiac
      rehabilitation participation is crucial for all post-myocardial infarction
      patients, particularly for the vulnerable socioeconomic populations.

PMID- 29589674
TI  - Reperfusion in STEMI patients: still a role for cardioprotection?
AB  - Ischemic heart disease remains a leading cause of death worldwide, responsible
      for an estimated 17.5 million deaths in 2012. Mortality from ST-elevation
      myocardial infarction STEMI have decreased over the last 3 decades. However,
      despite the success of reperfusion therapy by primary percutaneous coronary
      intervention (PPCI) or thrombolysis, STEMI is still of significant concern. A
      recent patient-level meta-analysis emphasized the pivotal importance of infarct
      size within 1 month after PPCI as a determinant of all-cause mortality and
      hospitalization for heart failure at 1 year. Although timely and complete
      reperfusion is the most effective way of limiting infarct size (IS) and
      subsequent ventricular remodeling, reperfusion per se adds an additional
      component of irreversible injury to the myocardium (known as ischemia/reperfusion
      injury, IRI), and the coronary circulation and it contributes to final infarct
      size. The prevention and treatment of lethal IRI and coronary microvascular
      dysfunction pose a continued and formidable barrier to successful myocardial
      perfusion as opposed to establishing patency of the epicardial infarct-related
      artery (IRA), and in this context the need for additional cardioprotective
      strategies to reduce IS and coronary microvascular dysfunction remains the 'last
      frontier' of reperfusion therapy.

PMID- 29589675
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: risk factors
      for morbidity and postoperative outcome.
AB  - BACKGROUND: Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) represents a treatment option for peritoneal surface
      malignancies. Even if it has been reported that this new approach improved
      survival of selected patients, it's still associated with high morbidity and
      mortality rates. METHODS: From October 1995 to December 2017, over 450 patients
      patients affected by peritoneal carcinomatosis (PC) underwent in our Institute to
      CRS associated with HIPEC. For this preliminary analysis we considered 300
      patients presenting PC of different origin: pseudomyxoma peritonei (PMP, n = 98),
      epithelial ovarian cancer (EOC, n = 87), peritoneal mesothelioma (DMPM, n = 49)
      and colorectal cancer (CRC, n = 66). Postoperative morbidity and mortality were
      studied in order to identify possible risk factors. RESULTS: The morbidity rate
      was 36.3% in all procedures (109/300). According to Dindo - Clavien
      Classification, 67 cases (22.3%) were associated with grade I-II complications
      and 35 cases(11.7%) with grade III-IV. Surgical and medical complication rates
      were 8.3% (25/300) and 11.3% (34/300), respectively. The mortality rate was 2.3%.
      Reoperation was needed in 28 patients (9.3%). The operative time, the number of
      anastomosis, of peritonectomy procedures, of visceral resections performed and
      the PCI value resulted the most statistically significant factors influencing
      postoperative morbidity and mortality. CONCLUSIONS: The risks of perioperative
      morbidity and mortality after CRS and HIPEC are analogous to any other major
      gastrointestinal surgery. CRS and HIPEC should remain a treatment option for
      highly selected patients in whom a curative or life prolonging treatment is a
      pursuit and should be performed in high volume specialized institutions.

PMID- 29589676
TI  - Gallbladder neuroendocrine carcinoma: metastasis or synchronous tumor?

PMID- 29589677
TI  - De-escalating oncoplastic breast surgery.

PMID- 29589678
TI  - Breast conservation following neoadjuvant therapy for breast cancer.

PMID- 29589679
TI  - Axillary surgery in breast cancer: the beginning of the end.
AB  - Axillary surgery in breast cancer patients has shifted from more extensive to
      minimalist approaches with re-evaluation of the risks versus benefits of
      available treatment options which are increasingly tailored to individual patient
      characteristics. A radical axillary node dissection is rarely indicated nowadays
      due to several factors including screening with detection of small node negative
      cancers, introduction of targeted node sampling, less reliance on information
      from nodal staging for adjuvant therapy decision making and evidence that non
      surgical treatments such as systemic therapies (chemotherapy, hormonal therapy,
      biological therapy) together with radiotherapy can safely treat low burden
      axillary disease. Sentinel lymph node biopsy (SLNB) alone with omission of
      further axillary surgery for nodal macrometastases (>2 mm) might be sufficiently
      extirpative to achieve local control when combined with adjuvant treatments.
      There remain unanswered questions on the safety of SLNB post chemotherapy in
      patients with biopsy-proven nodal disease at presentation and whether omission of
      axillary node dissection is feasible in selected cases. Emerging evidence
      suggests that a complete radiological response with removal of at least 3 nodes
      (including clipped nodes at time of biopsy) can yield false negative rates of
      <10% and be a safe option. New technologies involving percutaneous biopsy of
      sentinel nodes under radiological guidance are under investigation and could
      potentially replace surgical staging of the axilla in the future. Moreover,
      omission of any type of node biopsy might be a potential option in more favorable
      tumors and could herald the beginning of the end for histological axillary
      sampling in selected cases.

PMID- 29589680
TI  - Management of ductal carcinoma in situ in the modern era.
AB  - Ductal carcinoma in situ (DCIS) has been the subject of much controversy since
      the advent of population based breast screening programs. An increasing number of
      asymptomatic women are being diagnosed with this condition and there is
      uncertainty over the best treatment algorithm for this condition if treatment is
      to be considered at all. Different subtypes of DCIS show innate differences in
      developmental pathways and biological behavior. This is not only determined by
      pathological subtypes but there is increasing understanding of molecular
      biomarkers related to DCIS progression. The ultimate management aim is to
      identify a subgroup of patients in whom DCIS will not progress to invasive
      disease such that they can avoid morbidity from surgical and adjuvant therapies.
      This has to be balanced by the potential risk of undertreatment of patients in
      whom DCIS is likely to progress to invasive cancer and hence a reduced life
      expectancy. Results of current ongoing prospective randomized trials assessing
      the safety of omitting surgery for what is considered to be low risk DCIS are
      eagerly awaited for by patients and clinicians. However the definition of what is
      considered to be "low risk" DCIS is still to be ascertained.

PMID- 29589681
TI  - ?
AB  - The drug industry has a poor public image. Although its role is to treat disease,
      it has a poorer reputation than cigarette makers or the automotive industry. This
      situation must be analysed from three overlapping points of view: 1) the
      complexity of a market, in which most of the costs are hidden; 2) the difficulty
      of a connected society to organize debates on political questions related to
      basic values, and finally 3) the pervading distinction between morality and
      profits. This clarification might help the industry to become a fully fledged
      actor in the field of healthcare in order to participate in the improvement of
      the healthcare offer for the population.

PMID- 29589682
TI  - [Factors associated with the strength of organizational culture in a Beninese
      hospital].
AB  - INTRODUCTION: Organizational culture, a frequently ignored concept, affects job
      satisfaction and productivity in organizations. OBJECTIVE: To determine the
      factors associated with the strength of organizational culture (OC) in Mono /
      Couffo regional hospital in Lokossa in Benin. METHODS: This cross-sectional and
      analytical study involved 121 workers of Mono/Couffo hospital in March 2015. Data
      on the strength of OC was collected using a questionnaire based on the validated
      tool proposed by Cameron and Quinn (2006). Logistic regression was performed to
      explore the nature of the relationship between the independent variables and OC
      using Odds ratios. RESULTS: 62% of the surveyed subjects had a positive
      perception of organizational culture. This perception was statistically
      associated with managerial factors (moral support of workers and type of
      relationship with the executive staff). The risk of perceiving a low strength of
      OC was sixfold higher OR = 3.78, 95% CI (1.08 - 13.22) among subjects who felt
      they did not have moral support from executive staff than in those who perceived
      this moral support. The risk of perceiving a weak OC was higher among subjects
      who considered relations with the staff to be uncordial [OR = 14.32, 95% CI (4.35
      - 47.11)] compared to those who considered these relations to be cordial.
      CONCLUSION: Human resource management factors were more closely associated with
      the strength of organizational culture. Hospital managers should pay more
      attention to these factors in their hospitals to promote better institutional
      performance.

PMID- 29589683
TI  - [Coexistence of maternal overweight or obesity and stunted children in south
      western Benin households].
AB  - INTRODUCTION: To determine the prevalence and determinants of coexistence of
      maternal overweight or obesity and stunted children (DBM / SCOM) in south-western
      Benin households. METHODS: This cross-sectional study was carried out in June
      2015 on 357 mother-child pairs randomly selected by a two-stage sampling
      technique in the city of Come and its surroundings. Data on socio-economic
      factors, family, health care, dietary quality were collected by questionnaires,
      observation and documentary review. Anthropometric measurements were performed in
      mothers and children. A logistic regression analysis model was used to search for
      determinants of the coexistence of the two aspects of malnutrition. RESULTS:
      19.3% of mothers were overweight and 5.7% were obese. 46% of children were
      stunted. The prevalence of DBM / SCOM was 11.5%. The main factors associated with
      DBM/SCOM were the child's age, the mother's occupation, ethnicity, social status
      and educational level, and the size, economic level, transportation means and
      food insecurity of the household. CONCLUSION: A high frequency of the coexistence
      of maternal overweight or obesity and stunting was observed in Come households.
      Interventions based on the identified determinants are needed to act
      simultaneously on the double burden of malnutrition in Come.

PMID- 29589684
TI  - [Occupational risk factors and perceptions of air pollution by motorcycle taxi
      drivers in Cotonou, Benin].
AB  - INTRODUCTION: Motorcycle taxis occupy a major place in urban transport.
      Motorcycle taxi drivers are exposed to occupational risk factors (ORF) including
      air pollution. The objective of this study was to evaluate these ORF among
      motorcycle taxi drivers and their perceptions of air pollution. METHODS: This
      mixed study was conducted on motorcycle taxi drivers in Cotonou. The qualitative
      study was based on focus groups concerning 16 items from the Participatory
      Occupational Risk Screening Guide (DEPARIS) until saturation and after
      triangulation of data. The quantitative study consisted of administering a
      questionnaire addressing socioeconomic and demographic characteristics,
      cardiopulmonary diseases, and perception of air -pollution risk factors among 397
      Cotonou motorcycle taxi drivers. RESULTS: Drivers perceived poor road conditions,
      effort and handling, and lack of social security as unsatisfactory ORF. Their
      mean age was 40.95 +/- 8.75 years and 45.84% had primary -education. They had
      been working as motorcycle taxi drivers for an average of 134.95 +/- 101.53
      months with an average income of FCFA 3138 +/- 1238. These occupational factors
      were significantly associated with cardiopulmonary disorders, observed in 63.2%
      of drivers. Less than 1/3 of drivers felt that air pollution affected their
      personal health. CONCLUSION: Motorcycle taxi drivers have a poor perception of
      ORF and the severity of exposure to air pollution in this occupation. There is a
      need to take action to promote the health of this population.

PMID- 29589685
TI  - [Impact of children with multiple disabilities on families in Abidjan].
AB  - INTRODUCTION: A child's multiple disabilities have a major impact on families in
      both developed and developing countries. In Cote d'Ivoire, very few data are
      available concerning the real experiences of families of children with multiple
      disabilities. The objective of this study was to improve our knowledge of the
      impact of children with multiple disabilities on families in Cote d'Ivoire.
      METHODS: A qualitative study was conducted among the families consulting the
      Child Guidance Centre of the National Institute of Public Health in Abidjan. Data
      were collected in May 2015 by semi-structured individual interviews with mothers
      of children with multiple disabilities. RESULTS: Twenty mothers of multiply
      disabled children between the ages of 2 and 14 years were interviewed. The
      child's multiple disability was found to have a negative impact on finances,
      health, and social life. Health check-ups, treatment and transport are the main
      additional costs. Mothers suffer from insomnia, fatigue, back pain and anxiety
      and were often held responsible for their child's disability. A disabled child
      was a source of discord in several couples and a cause of school drop-out in some
      families.This study partially addresses the experiences of families with children
      with multiple disabilities. It confirms the results of several other studies,
      highlighting the vulnerability and social dysfunction of these families.
      CONCLUSION: The presence of a child with multiple disabilities in a family is a
      source of psychological, financial and social upheaval. This study raises
      questions about the impact of multiple disabilities on the whole family and a
      more detailed analysis of economic aspects.

PMID- 29589687
TI  - [User Associations and Multiple Sclerosis: Impact of Neoliberalism in France on
      the trajectory of life].
AB  - INTRODUCTION: Multiple sclerosis is a neurological disease that induces
      limitation of bodily performance. It has a major impact on the work and social
      life of affected persons because the patient's disability, often in the absence
      of visible symptoms, is o source of incomprehension in a society marked by the
      neoliberal dogma of performance. Patient associations often provide support for
      patients in their trajectory. OBJECTIVE: The aim of this research was to identify
      how the principles of neoliberalism manifest themselves in the discourse of
      multiple sclerosis subjects, to understand the effects of neoliberal integration,
      and to clarify the role played by the association involvement in the trajectories
      of life. METHODS: This qualitative study was based on 30 individual interviews
      and 4 group interviews with patients, as well as 23 observations of patient group
      meetings and focus groups. Ten people met in interviews also kept a mini-diary,
      in order to record their daily involvement in a patient association. Data were
      analysed thematically, initially independently then by cross-linked AtlasTi
      software. RESULTS: The association constitutes two forms, practical and
      ideological, an illustration of the resistance to neoliberalism, particularly in
      the form of individual and collective responsibilities. However, to a certain
      extent, it also recreates performance spaces. CONCLUSION: From a practical point
      of view, this research re-affirms the need to create collective activities to
      accompany people with chronic illness.

PMID- 29589688
TI  - [Breastfeeding promotion among deprived women in Haute-Normandie].
AB  - OBJECTIVES: The prevalence of breastfeeding in France is lower among deprived
      women than in the rest of the population. The Haute-Normandie region is severely
      affected by deprivation, especially among women. PRIMARY OBJECTIVE: To describe
      breastfeeding promotion in deprived women living in Haute-Normandie. Secondary
      objectives: to describe the prevalence of breastfeeding and identify barriers to
      breastfeeding in the same population. METHODS: This cross-sectional observational
      study was carried out in Haute-Normandie between March and June 2015, in three
      steps: 1) mailing questionnaires to actors working with deprived women, 2)
      analysis of child health certificates and 3) sociological interviews with 15
      deprived women. RESULTS: Only 4 of the 29 responding structures had implemented
      actions to promote breastfeeding among deprived women, with positive feed-back.
      Barely half of all deprived women had initiated breastfeeding in Haute-Normandie
      (Eure: 50%, Seine-Maritime: 54%). Finally, the same factors usually known to
      affect breastfeeding and its duration were also identified among deprived women
      living in Haute-Normandie. CONCLUSION: Guidelines for actions to support breast
      feeding among deprived mothers have been developed to guide local policies
      designed to reduce social inequalities in health in Haute-Normandie.

PMID- 29589689
TI  - [Interventions for smoking cessation among low socioeconomic status smokers: a
      literature review].
AB  - INTRODUCTION: In most western countries, smoking appears to be highly
      differentiated according to socio-economic level. Two systematic reviews
      published in 2014 showed that most of the recommended interventions for smoking
      cessation, particularly individual interventions, tend to increase social
      inequalities in health. An analysis of the most recent literature was carried out
      in order to provide policy makers and stakeholders with a set of evidence on the
      modalities of interventions to encourage and help disadvantaged smokers quit
      smoking. METHODS: This review was based on articles published between January
      2013 and April 2016. Only studies conducted in European countries or countries in
      stage 4 of the tobacco epidemic (USA, Canada, Australia, New Zealand) were
      included. Selected articles were double-screened. RESULTS: Twenty-three studies
      were identified, including evaluation of media campaigns, face-to-face
      behavioural support, phone- and web-based support or awareness of passive smoking
      among children. Some interventions adapted to precarious populations have been
      shown to be effective. CONCLUSIONS: Some characteristics would facilitate access
      and improve the support of disadvantaged groups, including a local intervention,
      a proactive approach and co-construction with targeted smokers.

PMID- 29589690
TI  - ?

PMID- 29589691
TI  - ?

PMID- 29589692
TI  - [The advantages of a third party in the "work organization" of head nurses.]
AB  - The organisation of production of care is a task that requires three different
      levels of competence: operational, structural and learning skills. The
      organisational requirements (OR) of the Head Nurse (HN) are often centered on the
      operational level, to the detriment of the other two levels. This difficulty is
      due to the organisation which presents limited political, cognitive and pragmatic
      levels of rationality.The aim of this study was to identify the impact of a third
      party in relation to the organisation and its effect on the HN's OR. An
      educational device places HN students in the position of a third party to allow
      them to work on an organisational problem delegated by a HN. The research
      intervention followed 17 projects over a period of one year.Intervention by a
      third party legitimised the problem by recognizing the difficulties in nursing
      and reconfiguring relations between healthcare professionals in a political
      dimension. The methods employed by the third party reassured the HN and completed
      their knowledge, placing particular focus on the importance of methodology and
      managerial posture. In practice, the third party supported the HN's power to act
      and coordinate the various members of the team. The third party contributes to
      the development of the HN's OR and completes certain limits of the HN's
      rationality. Nevertheless, difficulties still remain in the development of
      practices outside the medical team, limiting the extension to other services.A
      unit managerial support, a collective schedule and open spaces of discussion are
      recommended to bring structure and support to the OR.

PMID- 29589693
TI  - [Impact of dissemination of a diet and physical activity pamphlet to 8th grade
      students in France].
AB  - INTRODUCTION: "J'aime manger, j'aime bouger, le guide nutrition pour les
      adolescents", ("I love to eat and move, the nutrition pamphlet for teenagers"),
      which is one of the eight information guides of the French Nutritional and Health
      Programme, is distributed annually by Sante publique France, the national public
      health agency, to 8th grade students by their biology teachers. The aim of this
      study was to assess the impact of this dissemination plan and the way 8th grade
      students and biology teachers perceive the pamphlet. Teenagers' knowledge of the
      French Nutritional and Health Programme's recommendations was also assessed.
      METHODS: This study was based on a mixed method and was conducted in 2015 on 432
      8th grade students by face-to-face interviews at home and 20 8th grade biology
      teachers interviewed individually or during focus groups. RESULTS: The pamphlet
      obtained a recognition score of 40% among young people, who mostly saw it during
      a course at high school. 30% of teenagers reported having read or only skimmed
      through it and more than three-quarters reported that they liked the pamphlet.
      Teenagers and teachers found the pamphlet clear and accessible and globally
      appreciated the content, but they considered that it could be modernized.
      CONCLUSION: Systematic distribution of the guide to students of a specific school
      grade is an efficient strategy to reach a maximum number of young people. It
      should be continued in the future. Modernization of the guide and improved
      support to teachers to distribute the guide could improve the performance of the
      programme.

PMID- 29589694
TI  - [Emergence of the patient-actor in patient safety in France. A narrative review
      in social sciences and public health].
AB  - INTRODUCTION: For the last forty years, patients have been encouraged to take
      part in their care and to participate in improving the quality and safety of
      care. This phenomenon requires reflection on the conditions of emergence of this
      new role and its public health implications, particularly in the field of patient
      safety. METHODS: A narrative review of the international literature was conducted
      by searching Medline, Cairn and Persee databases. RESULTS: The database query
      identified 2,206 documents, 106 of which were included in the analysis. The
      emergence of the patient-actor is linked to sanitary crises and promoted by
      patient associations in the field of patient safety such as le Lien. This
      movement induces a transformation of the patient's role beyond the theme of
      patient safety: it revolutionizes the patient's contribution to the health
      system. CONCLUSION: This narrative review of the literature highlights the way in
      which health crises have encouraged the emergence of a new actor: the patient
      actor, accompanied by new semantics concerning the power of the patient. The
      patient occupies a specific place in the field of safety of care. In
      collaboration with healthcare professionals, the patient must constitute a
      resource to improve patient safety. The various contributions of patients are
      described and an analysis of the acceptability of patient participation is
      proposed.

PMID- 29589695
TI  - [Standing Orders and Quality of Care at Triage in Emergency Services: Integrative
      Review].
AB  - INTRODUCTION: Overcrowding of emergency services is a widespread problem in
      western countries. This situation results in negative patient outcomes and
      influences the quality of care. Standing orders are a possible way to improve the
      quality and performance of the health system. The aim of this article is to
      identify, based on a review of the literature, the effects of standing orders
      initiated by triage nurses in emergency services on the quality of care. METHODS:
      The quality of care dimensions of the Institute of Medicine (2001) were used as a
      frame of reference. The integrative review was performed on a selection of
      articles from Cochrane, CINALH, EMBASE, Medline, PubMed and Google Scholar. A
      total of 23 articles were selected and analysed. RESULTS: The integrative review
      documented the effects of standing orders initiated by triage nurses on the six
      dimensions of quality of care: effectiveness, patient-centeredness, efficiency,
      timeliness, safety and equity. Standing orders are able to improve the efficiency
      of care by reducing, among other things, the time to treatment and diagnostic
      tests. They also reduce the length of stay of patients in emergency services.
      CONCLUSION: Standing orders initiated by triage nurses in emergency services can
      have positive effects on the quality of care provided to the patient. Further
      research with more robust study designs is needed.

PMID- 29589697
TI  - Exhibition of Instruments.

PMID- 29589696
TI  - [Palliative care pathways of older patients].
AB  - INTRODUCTION: To determine the palliative care pathways of older patients in
      Sherbrooke, Qc by examining their transfers to other facilities. METHODS: This
      analysis was conducted by linking 3 databases: emergency department,
      hospitalizations and nursing homes. The study period ranged from January 2011 to
      December 2015. SPSS was used for statistical analysis. The study only included
      palliative care patients. RESULTS: 25% of patients waited less than 7 days for
      transfer, and 74% waited less than 3 weeks. 64.9% of patients were transferred to
      a long-term facility for dependent adults (LTF), 15.2% returned home or were
      transferred to private accommodation, and 15.9% were transferred to an
      intermediate care facility. One-half of patients subsequently changed facility,
      mainly those in homes or intermediate care. Palliative care patient bed
      occupation rates represented 1% of available bed-days and less than 2% of total
      beds for 86.4% of days. Only 12% of patients returned to hospital within 90 days
      after discharge. CONCLUSION: The number of beds occupied by palliative care
      patients does not seem to disrupt the hospital capacity. The majority of the
      palliative care patients were well managed, as reflected by the low readmission
      rate. Our results indicate good management of transfers and an adequate supply of
      long-term care facilities and home services.

PMID- 29589699
TI  - Exhibition of Specimens.

PMID- 29589698
TI  - Exhibition of Instrument.

PMID- 29589700
TI  - Exhibition of Instruments.

PMID- 29589701
TI  - Exhibition of Pathological Specimens.

PMID- 29589703
TI  - Exhibition of Instruments.

PMID- 29589704
TI  - Exhibition of Photograph.

PMID- 29589702
TI  - Exhibition of Pathological Specimens.

PMID- 29589705
TI  - Exhibition of Patient.

PMID- 29589706
TI  - Exhibition of Instrument.

PMID- 29589708
TI  - Exhibition of Patient.

PMID- 29589707
TI  - Exhibition of Specimens.

PMID- 29589709
TI  - Demonstration of Instruments.

PMID- 29589710
TI  - Exhibition of Specimen.

PMID- 29589711
TI  - Exhibition of Patients.

PMID- 29589712
TI  - Exhibition of Drawings and Photographs.

PMID- 29589713
TI  - Exhibition of Specimens.

PMID- 29589714
TI  - Exhibition of Patient.

PMID- 29589716
TI  - Exhibition of Specimens.

PMID- 29589715
TI  - Exhibition of Specimen.

PMID- 29589717
TI  - Exhibition of Specimens.

PMID- 29589718
TI  - Exhibition of Charts.

PMID- 29589720
TI  - Exhibition of Pathological Specimens.

PMID- 29589719
TI  - Exhibition of Patients.

PMID- 29589722
TI  - Exhibition of Patients.

PMID- 29589723
TI  - Exhibition of Patient.

PMID- 29589721
TI  - Exhibition of Patient.

PMID- 29589724
TI  - Exhibition of Patient.

PMID- 29589725
TI  - Exhibition of Pathological Specimen.

PMID- 29589726
TI  - Exhibition of Pathological Specimens.

PMID- 29589727
TI  - Exhibition of Instruments.

PMID- 29589728
TI  - Exhibition of Patients.

PMID- 29589729
TI  - Exhibition of Microscopical Sections and Drawings.

PMID- 29589730
TI  - Exhibition of Pathological Specimens.

PMID- 29589731
TI  - Exhibition of Pathological Specimens.

PMID- 29589732
TI  - Exhibition of Patient.

PMID- 29589733
TI  - Exhibition of Specimens.

PMID- 29589734
TI  - Exhibition of Specimens.

PMID- 29589735
TI  - Exhibition of Specimens.

PMID- 29589736
TI  - Exhibition of Pathological Specimens.

PMID- 29589737
TI  - Exhibition of Pathological Specimens.

PMID- 29589738
TI  - Correction to A Yeast Telomerase Complex Containing the Est1 Recruitment Protein
      Is Assembled Early in the Cell Cycle

PMID- 29589739
TI  - Thermal Lithiated-TiO2: A Robust and Electron-Conducting Protection Layer for Li
      Si Alloy Anode.
AB  - Developing new electrode materials with high capacity and stability is an urgent
      demand in electric vehicle applications. Li xSi alloy, as a promising high
      capacity and Li-containing anode candidate, has attracted much attention.
      However, the alloy anode suffers severely from intrinsic high chemical reactivity
      and poor cycling stability in battery fabrication and operation. Here, we have
      developed a facile coating-then-lithiation approach to prepare lithiated-TiO2
      protected Li xSi nanoparticles (Li xSi-Li2O/Ti yO z NPs) as an attractive anode
      material. The robust lithiated-TiO2 protection matrix not only provides fast
      electron transport pathways to efficiently improve the electrical conductivity
      between Li xSi/Si NPs, but also spatially limits the direct solid electrolyte
      interphase formation on Li xSi/Si cores during cycling. More importantly, this
      dense coating layer protects most inner Li xSi alloys from ambient corrosion,
      leading to high dry-air stability. As a result, the resulting Li xSi-Li2O/Ti yO z
      anode achieves greatly enhanced cycling and chemical stability in half-cells. It
      maintains capacity of about 1300 mAh g-1 after prolonged 500 cycles at a high
      current rate of C/2, with 77% capacity retention. In addition, it exhibits
      excellent dry-air stability, with around 87% capacity retained after exposure to
      dry air (10% relative humidity) for 30 days.

PMID- 29589740
TI  - Stokes-Shift-Engineered Indium Phosphide Quantum Dots for Efficient Luminescent
      Solar Concentrators.
AB  - Luminescent solar concentrators (LSCs) show promise because of their potential
      for low-cost, large-area, and high-efficiency energy harvesting. Stokes shift
      engineering of luminescent quantum dots (QDs) is a favorable approach to suppress
      reabsorption losses in LSCs; however, the use of highly toxic heavy metals in QDs
      constitutes a serious concern for environmental sustainability. Here, we report
      LSCs based on cadmium-free InP/ZnO core/shell QDs with type-II band alignment
      that allow for the suppression of reabsorption by Stokes shift engineering. The
      spectral emission and absorption overlap was controlled by the growth of a ZnO
      shell on an InP core. At the same time, the ZnO layer also facilitates the
      photostability of the QDs within the host matrix. We analyzed the optical
      performance of indium-based LSCs and identified the optical efficiency as 1.45%.
      The transparency, flexibility, and cadmium-free content of the LSCs hold promise
      for solar window applications.

PMID- 29589741
TI  - LC/MS/MS Bioanalysis of Protein-Drug Conjugates-The Importance of Incorporating
      Succinimide Hydrolysis Products.
AB  - Bioanalysis of antibody-drug conjugates (ADCs) is challenging due to the complex,
      heterogeneous nature of their structures and their complicated catabolism. To
      fully describe the pharmacokinetics (PK) of an ADC, several analytes are commonly
      quantified, including total antibody, conjugate, and payload. Among them,
      conjugate is the most challenging to measure, because it requires detection of
      both small and large molecules as one entity. Existing approaches to quantify the
      conjugated species of ADCs involve a ligand binding assay (LBA) for conjugated
      antibody or hybrid LBA/liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      for quantitation of conjugated drug. In our current work for a protein-drug
      conjugate (PDC) using the Centyrin scaffold, a similar concept to ADCs but with
      smaller protein size, an alternative method to quantify the conjugate by using a
      surrogate peptide approach, was utilized. The His-tagged proteins were isolated
      from biological samples using immobilized metal affinity chromatography (IMAC),
      followed by trypsin digestion. The tryptic peptide containing the linker attached
      to the payload was used as a surrogate of the conjugate and monitored by LC/MS/MS
      analysis. During method development and its application, we found that hydrolysis
      of the succinimide ring of the linker was ubiquitous, taking place at many stages
      during the lifetime of the PDC including in the initial drug product, in vivo in
      circulation in the animals, and ex vivo during the trypsin digestion step of the
      sample preparation. We have shown that hydrolysis during trypsin digestion is
      concentration-independent and consistent during the work flow-therefore, having
      no impact on assay performance. However, for samples that have undergone
      extensive hydrolysis prior to trypsin digestion, significant bias could be
      introduced if only the non-hydrolyzed form is considered in the quantitation.
      Therefore, it is important to incorporate succinimide hydrolysis products in the
      quantitation method in order to provide an accurate estimation of the total
      conjugate level. More importantly, the LC/MS/MS-based method described here
      provides a useful tool to quantitatively evaluate succinimide hydrolysis of ADCs
      in vivo, which has been previously reported to have significant impact on their
      stability, exposure, and efficacy.

PMID- 29589742
TI  - A Novel Redox Precipitation to Synthesize Au-Doped alpha-MnO2 with High
      Dispersion toward Low-Temperature Oxidation of Formaldehyde.
AB  - A novel method of redox precipitation was applied for the first time to
      synthesize a Au-doped alpha-MnO2 catalyst with high dispersion of the Au species.
      Au nanoparticles (NPs) can be downsized into approximate single atoms by this
      method, thereby realizing highly efficient utilization of Au element as well as
      satisfying low-temperature oxidation of formaldehyde (HCHO). Under catalysis of
      the optimal 0.25% Au/alpha-MnO2 catalyst, a polluted stream containing 500 ppm
      HCHO can be completely cleaned at 75  degrees C with the condition of a weight
      hourly space velocity (WHSV) of 60000 mL/(g h). Meanwhile, the catalyst retains
      good activity for removal of low-concentration HCHO (about 1 ppm) at ambient
      temperature with a high WHSV, and exhibits a high tolerance to water and long
      term stability. Our characterization of Au/alpha-MnO2 and catalytic performance
      tests clearly demonstrate that the proper amount of Au doping facilitates
      formation of surface vacancy oxygen, lattice oxygen, and charged Au species as an
      active site, which are all beneficial to catalytic oxidation of HCHO. The
      oxidation of HCHO over Au-doped alpha-MnO2 catalyst obeys the Mars-van Krevelen
      mechanism as evidenced by in situ diffuse reflectance infrared Fourier transform
      spectroscopy.

PMID- 29589743
TI  - Correction to Integrating MS1 and MS2 Scans in High-Resolution Parallel Reaction
      Monitoring Assays for Targeted Metabolite Quantification and Dynamic 13C-Labeling
      Metabolism Analysis.

PMID- 29589744
TI  - White Light Emission from Cucurbituril-Based Host-Guest Interaction in the Solid
      State: New Function of the Macrocyclic Host.
AB  - Energy transfer and interchange are central for fabricating white light-emitting
      organic materials. However, increasing the efficiency of light energy transfer
      remains a considerable challenge because of the occurrence of "cross talk". In
      this work, by exploiting the unique photophysical properties of cucurbituril
      triggered host-guest interactions, the two complementary luminescent colors blue
      and yellow for white light emission were independently obtained from a single
      fluorophore dye rather than energy transfer. Further study suggested that the
      rigid cavity of cucurbiturils efficiently prevented the aggregation of the dye
      and improved its thermal stability in the solid state by providing a regular
      nanosized fence for each encapsulated dye molecule. As a result, a novel
      macrocycle-assisted supramolecular approach for obtaining solid, white light
      emitting organic materials with low cost, high efficiency, and easy scale-up was
      successfully demonstrated.

PMID- 29589745
TI  - Mechanisms of Se(IV) Co-precipitation with Ferrihydrite at Acidic and Alkaline
      Conditions and Its Behavior during Aging.
AB  - Understanding the form of Se(IV) co-precipitated with ferrihydrite and its
      subsequent behavior during phase transformation is critical to predicting its
      long-term fate in a range of natural and engineered settings. In this work,
      Se(IV)-ferrihydrite co-precipitates formed at different pH were characterized
      with chemical extraction, transmission electron microscopy (TEM), and X-ray
      absorption spectroscopy (XAS) to determine how Se(IV) is associated with
      ferrihydrite. Results show that despite efficient removal, the mode and stability
      of Se(IV) retention in the co-precipitates varied with pH. At pH 5, Se(IV) was
      removed dominantly as a ferric selenite-like phase intimately associated with
      ferrihydrite, while at pH 10, it was mostly present as a surface species on
      ferrihydrite. Similarly, the behavior of Se(IV) and the extent of its retention
      during phase transformation varied with pH. At pH 5, Se(IV) remained completely
      associated with the solid phase despite the phase change, whereas it was
      partially released back into solution at pH 10. Regardless of this difference in
      behavior, TEM and XAS results show that Se(IV) was retained within the
      crystalline post-aging products and possibly occluded in nanopore and defect
      structures. These results demonstrate a potential long-term immobilization
      pathway for Se(IV) even after phase transformation. This work presents one of the
      first direct insights on Se(IV) co-precipitation and its behavior in response to
      iron phase transformations.

PMID- 29589746
TI  - Risk of Silver Transfer from Soil to the Food Chain Is Low after Long-Term (20
      Years) Field Applications of Sewage Sludge.
AB  - The increasingly widespread usage of silver (Ag) nanoparticles has raised
      concerns regarding their environmental risk. The behavior of Ag and its transfer
      risk to the food chain were investigated using a long-term field experiment that
      commenced in 1942 in which Ag-containing sewage sludge was repeatedly applied to
      the soil (25 applications during 20 years). The speciation of the Ag in both the
      sludge and the soils retrieved from the long-term experimental archive was
      examined using synchrotron-based X-ray absorption spectroscopy, and extractable
      Ag concentrations from soils were determined using 0.01 M Ca(NO3)2 and 0.005 M
      DTPA. The total Ag in the sludge during the time period of 1942-1961 ranged from
      155 to 463 mg kg-1. These values are 1-2 orders of magnitude higher than those in
      currently produced sludge (ca. 0.5-20 mg kg-1). Long-term repeated applications
      of these sludges resulted in an increase of Ag in soils from 1.9 mg kg-1 in the
      control to up to 51 mg kg-1. The majority (>80%) of the Ag in both the sludge and
      the sludge-treated soils was present as insoluble Ag2S, thereby markedly reducing
      the bioavailability of this Ag. Concentrations of Ag in the archived crop samples
      were generally <0.70 mg kg-1 in edible tissues, much less than those in diets
      that may cause an adverse effects in animals and humans (>100 mg kg-1). These
      data indicate that the transfer of Ag (derived from both traditional Ag industry
      and current nano Ag industry) to the terrestrial food chain is limited.

PMID- 29589747
TI  - Photostable and Low-Toxic Yellow-Green Carbon Dots for Highly Selective Detection
      of Explosive 2,4,6-Trinitrophenol Based on the Dual Electron Transfer Mechanism.
AB  - Advances in the development of fluorescent carbon dots (CDs) for detecting nitro
      explosives have attracted great interest. However, developing long-wavelength
      luminescence CDs for highly selective determination of 2,4,6-trinitrophenol (TNP)
      and getting insight into the detection mechanism remain further to be
      investigated. Here, excitation-independent yellow-green emission CDs with good
      photostability and low biotoxicity were introduced for detecting TNP selectively.
      Then, two types of electron transfer (ET) processes including hydrogen-bond
      interaction-assisted ET and proton transfer-assisted ET are suggested to be
      responsible for their photophysical behavior. Finally, the visual detection of
      TNP has been successfully developed by a CD-based indicator paper. The facile,
      highly sensitive, and selective detection for TNP in both of a solution and a
      solid phase makes CDs potentially useful in environmental sensor applications.

PMID- 29589748
TI  - Biochemical and Structural Studies of the Interaction between ARAP1 and CIN85.
AB  - Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1
      (ARAP1), Cbl-interacting protein of 85 kDa (CIN85), and casitas B-lineage
      lymphoma (Cbl) play important roles in epidermal growth factor receptor (EGFR)
      internalization and recycling. In previous studies, ARAP1 was found to interact
      with CIN85, and their interaction attenuated the ubiquitination of EGFR. However,
      the molecular mechanism was still unclear. In this study, we first biochemically
      and structurally characterized the interaction between ARAP1 and CIN85, and found
      that the CIN85 SH3B domain bound to the ARAP1 PXPXXRX (except P) XXR/H/K motif
      with high affinity and specificity. Based on this binding model, we further
      predicted other potential CIN85 binding partners and tested their interactions
      biochemically. Moreover, our swapping data and structure alignment analysis
      suggested that the beta2-beta3 loops of the CIN85 SH3 domains and the
      H87ARAP1/E132CIN85 interaction were critical for ARAP1 binding specificity.
      Finally, our competitive analytical gel-filtration chromatography and isothermal
      titration calorimetry (ITC) results showed that ARAP1 could compete with Cbl for
      CIN85 binding, which provides a biochemical basis for the regulatory roles of
      ARAP1 in the CIN85-mediated EGFR internalizing process.

PMID- 29589749
TI  - Free-Standing Nanocrystalline Materials Assembled from Small Molecules.
AB  - We demonstrate a solution-based fabrication of centimeter-size free-standing
      films assembled from organic nanocrystals based on common organic dyes (perylene
      diimides, PDIs). These nanostructured films exhibit good mechanical stability,
      and thermal robustness superior to most plastics, retaining the crystalline
      microstructure and macroscopic shape upon heating up to 250-300  degrees C. The
      films show nonlinear optical response and can be used as ultrafiltration
      membranes. The macroscopic functional materials based on small molecules can be
      alternative or complementary to materials based on macromolecules.

PMID- 29589750
TI  - Argonaute Facilitates the Lateral Diffusion of the Guide along Its Target and
      Prevents the Guide from Being Pushed Away by the Ribosome.
AB  - Argonaute (AGO) proteins play central roles in nucleic acid-guided interference
      that regulates gene expression and defend against foreign genetic elements in all
      life. Although much progress has been made with respect to the function of
      argonaute proteins in target recognition and cleavage, the detailed mechanism of
      their biological functions is not fully understood. Here, using atomic force
      microscopy-based single-molecule force spectroscopy, we studied target-guide
      dissociation in the absence or presence of Thermus thermophilus AGO (TtAGO). Our
      results indicated that AGO changed the fundamental properties of target-guide
      interaction. Dissociation of the target from the guide is easier in the lateral
      direction of the nucleic acid in the presence of AGO protein but harder in the
      longitudinal direction. Our results support the idea that one-dimensional
      diffusion of the RNA-induced silencing complex (RISC) along the target strand is
      more efficient than three-dimensional diffusion and explain the priority of RISC
      binding over the ribosome complex during translation elongation.

PMID- 29589751
TI  - Total Synthesis of Biselyngbyolide B and Its C21-C22 Z-Isomer.
AB  - Investigations toward the synthesis of the 18-membered macrolactone
      biselyngbyolide B (2) from a C1-C13 and a C14-C23 fragment are described. As a
      key reaction in the synthesis of the C1-C13 fragment, we used an asymmetric
      propargylation of chiral vinylketene silyl N, O-acetal 12. Access to a C14-C23
      fragment featuring a skipped diene and a sensitive allyl alcohol function was
      initially attempted via reductive fragmentation of a pyran template. However,
      this ring opening on iodide 32 with t-BuLi led to dienynol 33 with a 21 Z double
      bond. With a silyl protecting group at 3-OH and by implementing an intramolecular
      Stille coupling for macrolactonization, the 21 Z-isomer of biselyngbyolide B (47)
      was obtained. For preparation of a C14-C23 fragment with the 21 E-configuration,
      a cross-coupling of vinylstannane 48 with 4-bromocrotonate (49) set the
      configuration of the two double bonds. Biselyngbyolide B (2) was then accessed by
      an intramolecular Heck coupling. In preliminary biological cytotoxicity assays, 2
      turned out to be active, whereas the 21 Z-isomer 47 was much less active. The 3
      OMEM analogue 40 was devoid of activity. These results support the notion that
      the side chain with the correct configuration is relevant for binding to the Ca2+
      ATPase and the biological activity.

PMID- 29589752
TI  - Computational Study of Microhydration in Sulfonated Diels-Alder Poly(phenylene)
      Polymers.
AB  - The nature of microhydration in sulfonated Diels-Alder poly(phenylene) (SDAPP)
      polymer membranes is explored using ab initio and density functional theory (DFT)
      electronic structure calculations. The impact of the aromatic poly(phenylene)
      structure, including cooperative effects between multiple spatially adjacent
      sulfonic groups, on the hydration environment is addressed using a series of DFT
      B3LYP/6-311**-optimized structures for different SDAPP. nH2O clusters. In
      addition, larger SDAPP polymer fragments, along with selected hydrophilic domain
      structures extracted from molecular dynamic (MD) simulations, are also evaluated
      using ONIOM HF/PM6 semiempirical calculations. The SDAPP clusters reveal that
      spontaneous proton dissociation occurs at low levels of hydration to form
      sulfonic-acid-associated H3O+ contact ion pairs (CIPs), which then evolve into
      solvated CIPs at higher hydration levels. For multiple sulfonic acid groups
      located on the poly(phenylene) side chains, the hydration energies are a function
      of the relative acid location and backbone configuration. Variations in the
      phenylene backbone torsional angles allow remote sulfonic acids to adopt an
      optimal separation to produce an extended hydrogen bonded network of waters
      between the SDAPP acids groups. These calculations provide a baseline to help
      describe the proton transport and hydration behavior of SDAPP membranes.

PMID- 29589753
TI  - Radical-Facilitated Green Synthesis of Highly Ordered Mesoporous Silica
      Materials.
AB  - In the hydrothermal synthesis of highly ordered mesoporous silica material SBA
      15, strong acid is typically required to catalyze the hydrolysis and condensation
      of silica species. Meanwhile, under strongly acidic conditions, the transition
      metal ions, e.g., iron ions, are difficult to incorporate into SBA-15 because of
      the facile dissociation of Fe-O-Si bonds. Here, we demonstrate an acid-free green
      synthetic strategy for the synthesis of highly ordered mesoporous SBA-15 and Fe
      SBA-15 with the assistance of hydroxyl free radicals that are generated by
      physical or chemical methods. The prepared materials exhibit a large specific
      surface area compared to the counterparts prepared by conventional method under
      acidic conditions. Moreover, Fe-SBA-15 shows high metal loading efficiency as
      over 50%. Density functional theory calculations suggest that the hydroxyl free
      radicals exhibit higher catalytic activity than H+ ions for the hydrolysis of
      tetraethyl orthosilicate. This radical-facilitated synthesis approach overcomes
      the challenge to the direct synthesis of highly ordered SBA-15 and Fe-SBA-15
      without adding any acid, providing a facile and environmentally friendly route
      for future large-scale production of ordered mesoporous materials.

PMID- 29589754
TI  - Phenothiazine Radical Cation Excited States as Super-oxidants for Energy
      Demanding Reactions.
AB  - We demonstrate that the 10-phenyl-10 H-phenothiazine radical cation (PTZ+*) has a
      manifold of excited doublet states accessible using visible and near-infrared
      light that can serve as super-photooxidants with excited-state potentials is
      excess of +2.1 V vs SCE to power energy demanding oxidation reactions.
      Photoexcitation of PTZ+* in CH3CN with a 517 nm laser pulse populates a Dn
      electronically excited doublet state that decays first to the unrelaxed lowest
      electronic excited state, D1' (tau < 0.3 ps), followed by relaxation to D1 (tau =
      10.9 +/- 0.4 ps), which finally decays to D0 (tau = 32.3 +/- 0.8 ps). D1' can
      also be populated directly using a lower energy 900 nm laser pulse, which results
      in a longer D1'->D1 relaxation time (tau = 19 +/- 2 ps). To probe the oxidative
      power of PTZ+* photoexcited doublet states, PTZ+* was covalently linked to each
      of three hole acceptors, perylene (Per), 9,10-diphenylanthracene (DPA), and 10
      phenyl-9-anthracenecarbonitrile (ACN), which have oxidation potentials of 1.04,
      1.27, and 1.6 V vs SCE, respectively. In all three cases, photoexcitation
      wavelength dependent ultrafast hole transfer occurs from Dn, D1', or D1 of PTZ+*
      to Per, DPA, and ACN. The ability to take advantage of the additional oxidative
      power provided by the upper excited doublet states of PTZ+* will enable
      applications using this chromophore as a super-oxidant for energy-demanding
      reactions.

PMID- 29589755
TI  - Ultrahigh Frequency Nanomechanical Piezoresistive Amplifiers for Direct Channel
      Selective Receiver Front-Ends.
AB  - Channel-selective filtering and amplification in ultrahigh frequency (UHF)
      receiver front-ends are crucial for realization of cognitive radio systems and
      the future of wireless communication. In the past decade, there have been
      significant advances in the performance of microscale electromechanical resonant
      devices. However, such devices have not yet been able to meet the requirements
      for direct channel selection at RF. They also occupy a relatively large area on
      the chip making implementation of large arrays to cover several frequency bands
      challenging. On the other hand, electromechanical piezoresistive resonant devices
      are active devices that have recently shown the possibility of simultaneous
      signal amplification and channel-select filtering at lower frequencies. It has
      been theoretically predicted that if scaled down into the nanoscale, they can
      operate in the UHF range with a very low power consumption. Here, for the first
      time nanomechanical piezoresistive amplifiers with active element dimensions as
      small as 50 nm * 200 nm are demonstrated. With a device area of less than 1.5
      MUm2 a piezoresistive amplifier operating at 730 MHz shows effective quality
      factor ( Q) of 89,000 for a 50Omega load and gains as high as 10 dB and Q of
      330,000 for a 250Omega load while consuming 189 MUW of power. On the basis of the
      measurement results, it is shown that for piezoresistor dimensions of 30 nm * 100
      nm it is possible to get a similar performance at 2.4 GHz with device footprint
      of less than 0.2 MUm2.

PMID- 29589756
TI  - Subnanometer Gold Clusters Adhere to Lipid A for Protection against Endotoxin
      Induced Sepsis.
AB  - Endotoxicity originating from a dangerous debris (i.e., lipopolysaccharide, LPS)
      of Gram-negative bacteria is a challenging clinical problem, but no drugs or
      therapeutic strategies that can successfully address this issue have been
      identified yet. In this study, we report a subnanometer gold cluster that can
      efficiently block endotoxin activity to protect against sepsis. The endotoxin
      blocker consists of a gold nanocluster that serves as a flakelike substrate and a
      coating of short alkyl motifs that act as an adhesive to dock with LPS by
      compacting the intramolecular hydrocarbon chain-chain distance ( d-spacing) of
      lipid A, an endotoxicity active site that can cause overwhelming cytokine
      induction resulting in sepsis progression. Direct evidence showed the d-spacing
      values of lipid A to be decreased from 4.19 A to either 3.85 or 3.54 A,
      indicating more dense packing densities in the presence of subnanometer gold
      clusters. In terms of biological relevance, the concentrations of key pro
      inflammatory NF-kappaB-dependent cytokines, including plasma TNF-alpha, IL-6, and
      IL-1beta, and CXC chemokines, in LPS-challenged mice showed a noticeable
      decrease. More importantly, we demonstrated that the treatment of antiendotoxin
      gold nanoclusters significantly prolonged the survival time in LPS-induced septic
      mice. The ultrasmall gold nanoclusters could target lipid A of LPS to deactivate
      endotoxicity by compacting its packing density, which might constitute a
      potential therapeutic strategy for the early prevention of sepsis caused by Gram
      negative bacterial infection.

PMID- 29589757
TI  - Mechanism of Charged, Neutral, Mono-, and Polyatomic Donor Ligand Coordination to
      Perchlorinated Cyclohexasilane (Si6Cl12).
AB  - We report the detailed computational study of several perchlorinated
      cyclohexasilane (Si6Cl12)-based inverse sandwich compounds. It was found that
      regardless of the donor ligand size and charge, for example, Cl- and CN- anions
      or neutral HCN and NCPh nitriles, their coordination to the puckered Si6Cl12 ring
      results in its flattening. The NBO and CDA studies of the complexes showed that
      coordination occurs due to hybridization of low-lying antibonding sigma*(Si-Cl)
      and sigma*(Si-Si) unoccupied molecular orbitals (UMOs) of Si6Cl12 and occupied
      molecular orbitals (OMOs) of donor molecules (predominantly lone-pair-related),
      resulting in donor-to-ring charge transfer accompanied by complex stabilization
      and ring flattening. It is known that the Si6 ring distortion results from
      vibronic coupling of OMO and UMO pairs (pseudo-Jahn-Teller effect, PJT).
      Consequently, the Si6 ring flattening most probably occurs due to suppression of
      the PJT effect in all of the studied compounds. In this paper, the stabilization
      energy E(2) associated with donor-acceptor charge transfer (delocalization) was
      estimated using NBO analysis for [Si6Cl12.2Cl]2-, [Si6Cl12.2(NC)]2-,
      Si6Cl12.2(NCH), and Si6Cl12.2(NCPh). It was found that the polarizability of the
      donor might significantly affect the stabilization energy value (Cl- > CN- >
      HCN). For the neutral complexes, the E(2) value is correlated with the charge on
      the nitrogen atoms. All of these factors, that is, specific donor E(2) value,
      charge transfer, complex MO energy diagrams, and so on, should be taken into
      account when choosing the ligands suitable for forming Si-based 1D compounds and
      other nanoscale materials.

PMID- 29589758
TI  - 3D Localized Trions in Monolayer WSe2 in a Charge Tunable van der Waals
      Heterostructure.
AB  - Monolayer transition metal dichalcogenides (TMDCs) have recently emerged as a
      host material for localized optically active quantum emitters that generate
      single photons. (1-5) Here, we investigate fully localized excitons and trions
      from such TMDC quantum emitters embedded in a van der Waals heterostructure. We
      use direct electrostatic doping through the vertical heterostructure device
      assembly to generate quantum confined trions. Distinct spectral jumps as a
      function of applied voltage bias, and excitation power-dependent charging,
      demonstrate the observation of the two different excitonic complexes. We also
      observe a reduction of the intervalley electron-hole exchange interaction in the
      confined trion due to the addition of an extra electron, which is manifested by a
      decrease in its fine structure splitting. We further confirm this decrease of
      exchange interaction for the case of the charged states by a comparative study of
      the circular polarization resolved photoluminescence from individual excitonic
      states. The valley polarization selection rules inherited by the localized trions
      will provide a pathway toward realizing a localized spin-valley-photon interface.

PMID- 29589760
TI  - Comment on the Principle of Detailed Balancing in Complex Mechanisms and Its
      Application to Iodate Reactions.

PMID- 29589761
TI  - Drop Capturing Based on Patterned Substrate in Space.
AB  - In this work, we introduced a method for capturing aqueous drop based on a
      patterned substrate in space. Through the manipulation test of a colloidal drop,
      it could be verified that this patterned substrate had excellent control ability
      for aqueous drop in microgravity condition. The confinement mechanism of this
      substrate was clarified, which showed that drops with different volume could be
      pinned and attracted at a given area on the substrate. The confinement capability
      was related to the gravity effect, and the patterned substrate could confine
      aqueous drops with larger volume under microgravity than in normal gravity. With
      advantages of simple operation and strong capability to control large drops, this
      technique exhibited the wide application prospect in the fields of fluid
      management, biosensing, and pharmacy in microgravity condition in the future.

PMID- 29589759
TI  - Light-Responsive Polymer Particles as Force Clamps for the Mechanical Unfolding
      of Target Molecules.
AB  - Single-molecule force spectroscopy techniques are powerful tools for
      investigating the mechanical unfolding of biomolecules. However, they are limited
      in throughput and require dedicated instrumentation. Here, we report a force
      generating particle that can unfold target molecules on-demand. The particle
      consists of a plasmonic nanorod core encapsulated with a thermoresponsive polymer
      shell. Optical heating of the nanorod leads to rapid collapse of the polymer,
      thus transducing light into mechanical work to unfold target molecules. The
      illumination tunes the duration and degree of particle collapse, thus controlling
      the lifetime and magnitude of applied forces. Single-molecule fluorescence
      imaging showed reproducible mechanical unfolding of DNA hairpins. We also
      demonstrate the triggering of 50 different particles in <1 min, exceeding the
      speed of conventional atomic force microscopy. The polymer force clamp represents
      a facile and bottom-up approach to force manipulation.

PMID- 29589762
TI  - 1H Nuclear Magnetic Resonance Based Metabolomics Approach Reveals the Metabolic
      Mechanism of (-)-5-Hydroxy-equol against Hepatocellular Carcinoma Cells in Vitro.
AB  - 1H nuclear magnetic resonance (NMR)-based metabolomics can rapidly detect
      metabolic shift under various stimulus; thus, it facilitated the dissection of
      the therapeutic mechanisms of compounds. (-)-5-Hydroxy-equol is an isoflavone
      metabolite that be obtained by microbial biotransformation. In the current work,
      the effect of (-)-5-hydroxy-equol on hepatocellular carcinoma (HCC) cells and its
      mechanism have been explored based on 1H NMR-based metabolomics approach. Our
      results revealed that (-)-5-hydroxy-equol can significantly inhibit the
      proliferation, migration, and invasion of SMMC-7721 cells and inhibit the
      proliferation of HepG2 cells. Metabolomics revealed that 17 differential
      metabolites involving in amino acid metabolism and energy metabolism were
      significantly changed inside and outside of the cells after treatment of (-)-5
      hydroxy-equol. Specifically, (-)-5-hydroxy-equol at a concentration of 30 MUM
      significantly decreased the concentrations of pyruvate, glutamate, and glucose.
      Because glycometabolism is a crucial feature of cancer-specific metabolism, we
      further verified enzymes and proteins that are closely relevant to
      glycometabolism. Our results indicated that (-)-5-hydroxy-equol-modulated
      glycolysis in HCC through the inhibition of activities of hexokinase,
      phosphofructokinase, and pyruvate kinase, and the expression of pyruvate kinase
      M2. This study revealed that metabolomic analysis integrating with further
      verifications at the biochemical level can facilitate understanding the anti-HCC
      mechanisms of (-)-5-hydroxy-equol.

PMID- 29589763
TI  - Dynamics of Long-Distance Hydrogen-Bond Networks in Photosystem II.
AB  - Photosystem II uses the energy of absorbed light to split water molecules,
      generating molecular oxygen, electrons, and protons. The four protons generated
      during each reaction cycle are released to the lumen via mechanisms that are
      poorly understood. Given the complexity of photosystem II, which consists of
      multiple protein subunits and cofactor molecules and hosts numerous waters, a
      fundamental issue is finding transient networks of hydrogen bonds that bridge
      potential proton donor and acceptor groups. Here, we address this issue by
      performing all-atom molecular dynamics simulations of wild-type and mutant
      photosystem II monomers, which we analyze using a new protocol designed to
      facilitate efficient analysis of hydrogen-bond networks. Our computations reveal
      that local protein/water hydrogen-bond networks can assemble transiently in
      photosystem II such that the reaction center connects to the lumen. The dynamics
      of the hydrogen-bond networks couple to the protonation state of specific
      carboxylate groups and are altered in a mutant with defective proton transfer.
      Simulations on photosystem II without its extrinsic PsbO subunit provide a
      molecular interpretation of the elusive functional role of this subunit.

PMID- 29589764
TI  - The alleviating effects of sesame oil on diazinon-induced toxicity in male wistar
      rats.
AB  - Pesticides are introduced into the environment in a variety of ways and
      constitute a wide group of environmental pollutants. To evaluate the attenuating
      effects of sesame oil on the toxicity of diazinon (DZN), male Wistar rats were
      exposed to DZN and/or sesame oil by gavage at different dosages for 8 weeks. DZN
      in a concentration of 30 mg/kg caused an increase in the number of white blood
      cell (WBCs), and the combination of DZN and sesame oil raised the number of
      platelets; the number of red blood cells, however, did not change. In addition,
      DZN caused a drastic decrease in the sperm count in a dose-dependent manner and
      in a concentration of 50 mg/kg, the sperm count decreased by more than 50%, but
      the combination of sesame oil in a dose of 4 ml/kg with DZN reversed the effect
      of this pesticide. The evidence presented here suggests that in addition to
      antioxidants, such as olive oil, intermittent exposure with sufficient intervals
      can decrease the toxicity of pesticides.

PMID- 29589765
TI  - Diaphragm Remodeling during Application of Positive End-Expiratory Pressure. A
      Case of Normal Physiologic Adaptation Gone Awry?

PMID- 29589766
TI  - Memory enhancing effect of Nigella Sativa hydro-alcoholic extract on
      lipopolysaccharide-induced memory impairment in rats.
AB  - In this study, the effects of Nigella Sativa (NS) hydro-alcoholic extract on
      lipopolysaccharide (LPS)-induced learning and memory impairments, hippocampal
      cytokine levels, and brain tissues oxidative damage were investigated in rats.
      The rats were grouped and treated: (1) control (saline), (2) LPS (1 mg/kg i.p.),
      and (3-5) 100, 200, or 400 mg/kg NS hydro-alcoholic extract 30 min before LPS
      injection. The treatment was started since 6 days before the behavioral
      experiments and continued during the behavioral tests (LPS injection 2 h before
      each behavioral experiment). Finally, the brains were removed for biochemical
      assessments. In Morris water maze (MWM) test, LPS increased the escape latency
      and traveled path compared to control group, whereas all doses of NS hydro
      alcoholic extract decreased them compared to LPS group. In passive avoidance (PA)
      test, the latency to enter the dark compartment in LPS group was shorter than
      control group while in all treated groups it was longer than LPS group. LPS
      increased tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      malondialdehyde (MDA), and nitric oxide (NO) metabolites, and decreased thiol
      content, superoxide dismutase (SOD), and catalase (CAT) in the hippocampal
      tissues compared to control group while NS hydro-alcoholic extract decreased MDA
      and NO metabolites and increased thiol content, SOD, and CAT compared to LPS
      group. Findings of the current study indicated that the hydro-alcoholic extract
      of NS improved the LPS-induced learning and memory impairments induced by LPS in
      rats by improving hippocampal cytokine levels and brain tissues oxidative damage.

PMID- 29589767
TI  - Magnetic-resonance-imaging-based three-dimensional muscle reconstruction of hip
      abductor muscle volume in a person with a transfemoral bone-anchored prosthesis:
      A feasibility study.
AB  - BACKGROUND: Persons with transfemoral amputation typically have severe muscle
      atrophy of the residual limb. The effect of bone-anchored prosthesis use on
      existing muscle atrophy is unknown. A potentially feasible method to evaluate
      this is magnetic resonance imaging (MRI)-based three-dimensional (3D) muscle
      reconstruction. We aimed to (1) examine the feasibility of MRI-based 3D muscle
      reconstruction technique in a person with a cobalt-chrome-molybdenum transfemoral
      bone-anchored prosthesis; and (2) describe the change of hip abductor muscle
      volume over time. METHODS: In this single case, 1-year follow-up study we
      reconstructed the 3D hip abductor muscle volumes semiautomatically from MRI scans
      at baseline, 6- and 12-month follow-up. The number of adverse events,
      difficulties in data analysis, time investment and participants' burden
      determined the level of feasibility. RESULTS: We included a man (70 years) with a
      transfemoral amputation who received a bone-anchored prosthesis after 52 years of
      socket prosthesis use. No adverse events occurred. The accuracy of the 3D
      reconstruction was potentially reduced by severe adipose tissue interposition.
      Data analysis was time-intensive (115 h). Participants' burden was limited to 3-h
      time investment. Compared to baseline, the total hip abductor volume of both the
      residual limb (6 month: 5.5%; 12 month: 7.4%) and sound limb (6 month: 7.8%; 12
      month: 5.5%) increased. CONCLUSION: The presented technique appears feasible to
      follow muscle volume changes over time in a person with a cobalt-chrome
      molybdenum transfemoral bone-anchored prosthesis in an experimental setting.
      Future research should focus on analysis of muscle tissue composition and the
      feasibility in bone-anchored prostheses of other alloys.

PMID- 29589769
TI  - Comparison of portable handheld versus fixed isokinetic dynamometers in measuring
      strength of the wrist and forearm.
AB  - PURPOSE: The purpose of this study was to test the concurrent validity of using
      hydraulic dynamometers in comparison to the gold standard isokinetic dynamometers
      in measuring wrist and forearm strength. MATERIALS AND METHODS: Healthy adults
      between the ages of 18-65 participated, including 24 participants, 8 men and 16
      women. The examiner used a handheld dynamometer, forearm/wrist dynamometer, and
      an isokinetic dynamometer to measure force/torque production in forearm rotation
      and wrist flexion/extension using a standardized protocol of two handle types for
      each motion. Sequence of testing was randomized. The data were analyzed using
      Pearson correlation coefficients and paired t-tests. RESULTS: When matched for
      handle type, three of the four correlations between the strength measurements
      taken with the different dynamometers were moderate to high with Pearson product
      moment coefficients ranging from 0.72 to 0.96; the screwdriver handle
      demonstrated less than acceptable correlation (r = 0.45, 0.67 for wrist flexion
      and extension, respectively). There were significant differences in most of the
      force/torque values obtained by different handle types for wrist and forearm
      motions. DISCUSSION AND CONCLUSIONS: Overall, the dynamometers demonstrated
      acceptable correlations supporting concurrent validity for measuring forearm and
      wrist strength, except with the screwdriver handle. However, different tools,
      positions, and handle interfaces provided different absolute values, therefore
      the tools cannot be used interchangeably. It is recommended that repeated
      measurements to monitor patient progress are taken with the same tool and handle
      type.

PMID- 29589768
TI  - IOC Consensus Statement: Dietary Supplements and the High-Performance Athlete.
AB  - Nutrition usually makes a small but potentially valuable contribution to
      successful performance in elite athletes, and dietary supplements can make a
      minor contribution to this nutrition program. Nonetheless, supplement use is
      widespread at all levels of sport. Products described as supplements target
      different issues, including the management of micronutrient deficiencies, supply
      of convenient forms of energy and macronutrients, and provision of direct
      benefits to performance or indirect benefits such as supporting intense training
      regimens. The appropriate use of some supplements can offer benefits to the
      athlete, but others may be harmful to the athlete's health, performance, and/or
      livelihood and reputation if an anti-doping rule violation results. A complete
      nutritional assessment should be undertaken before decisions regarding supplement
      use are made. Supplements claiming to directly or indirectly enhance performance
      are typically the largest group of products marketed to athletes, but only a few
      (including caffeine, creatine, specific buffering agents and nitrate) have good
      evidence of benefits. However, responses are affected by the scenario of use and
      may vary widely between individuals because of factors that include genetics, the
      microbiome, and habitual diet. Supplements intended to enhance performance should
      be thoroughly trialed in training or simulated competition before implementation
      in competition. Inadvertent ingestion of substances prohibited under the anti
      doping codes that govern elite sport is a known risk of taking some supplements.
      Protection of the athlete's health and awareness of the potential for harm must
      be paramount, and expert professional opinion and assistance is strongly advised
      before embarking on supplement use.

PMID- 29589770
TI  - ROS and RNS signalling: adaptive redox switches through oxidative/nitrosative
      protein modifications.
AB  - Over the last decade, a dual character of cell response to oxidative stress,
      eustress versus distress, has become increasingly recognized. A growing body of
      evidence indicates that under physiological conditions, low concentrations of
      reactive oxygen and nitrogen species (RONS) maintained by the activity of
      endogenous antioxidant system (AOS) allow reversible oxidative/nitrosative
      modifications of key redox-sensitive residues in regulatory proteins. The
      reversibility of redox modifications such as Cys S-sulphenylation/S
      glutathionylation/S-nitrosylation/S-persulphidation and disulphide bond
      formation, or Tyr nitration, which occur through electrophilic attack of RONS to
      nucleophilic groups in amino acid residues provides redox switches in the
      activities of signalling proteins. Key requirement for the involvement of the
      redox modifications in RONS signalling including ROS-MAPK, ROS-PI3K/Akt, and RNS
      TNF-alpha/NF-kB signalling is their specificity provided by a residue
      microenvironment and reaction kinetics. Glutathione, glutathione peroxidases,
      peroxiredoxins, thioredoxin, glutathione reductases, and glutaredoxins modulate
      RONS level and cell signalling, while some of the modulators (glutathione,
      glutathione peroxidases and peroxiredoxins) are themselves targets for redox
      modifications. Additionally, gene expression, activities of transcription
      factors, and epigenetic pathways are also under redox regulation. The present
      review focuses on RONS sources (NADPH-oxidases, mitochondrial electron
      transportation chain (ETC), nitric oxide synthase (NOS), etc.), and their cross
      talks, which influence reversible redox modifications of proteins as
      physiological phenomenon attained by living cells during the evolution to control
      cell signalling in the oxygen-enriched environment. We discussed recent advances
      in investigation of mechanisms of protein redox modifications and adaptive redox
      switches such as MAPK/PI3K/PTEN, Nrf2/Keap1, and NF-kappaB/IkappaB, powerful
      regulators of numerous physiological processes, also implicated in various
      diseases.

PMID- 29589771
TI  - Effect of oral exposure to acrylamide on biochemical and hematologic parameters
      in Wistar rats.
AB  - The toxic effects of ACR monomer include carcinogenesis, cellular genotoxic, and
      neurotoxicity. In this study, we examined the effect of acrylamide on biochemical
      and hematologic parameters in Wistar rats and explored the renal and hepatic
      function of these animals through a complementary anatomopathologic study. For
      it, thirty female Wistar rats aged 4 weeks and weighing 100 +/- 10 g were housed
      six animals per cage and divided as follows: two groups were exposed for 2 months
      to drinking water containing 5 mg (Group 2) or 10 mg acrylamide (Group 3); one
      group of 12 rats received the median lethal dose of acrylamide by gavage (Group
      4); and the control group (Group 1) received pure water. The results clearly
      showed that acrylamide affects various biochemical parameters, such as
      creatinine, urea, and serum globulin levels and the lipid balance, which are
      directly related to renal and hepatic dysfunction and disruption of the
      hematologic system. In addition, the data revealed changes in the complete blood
      count (CBC); significant increases in the number of leukocytes (9.95 +/- 1.44 and
      10.44 +/- 1.21) and lymphocytes (6.11 +/- 0.48 and 6.33 +/- 0.76) in Groups 3 and
      4, respectively; and decreases in total protein (88.95 +/- 6.36), albumin (37.65
      +/- 1.65) and alpha-1 globulin levels (24.84 +/- 2.10) in Group 3. The
      anatomopathologic study confirmed liver damage in the animals administered an
      acrylamide containing diet compared with those in the control group. The present
      study confirmed the effects of acrylamide on different hematologic, biochemical
      and immunologic parameters, with a specific focus on the liver and kidney, and on
      the induction of neurotoxic disorders. The results showed that oral exposure to
      acrylamide via drinking water or gavage induces kidney damage, hepatocellular
      insufficiency and chronic liver disease, resulting in primary immunodeficiency
      and activation of the immune system following the possible expression of certain
      immunoreaction genes.

PMID- 29589772
TI  - Alda-1, an ALDH2 activator, protects against hepatic ischemia/reperfusion injury
      in rats via inhibition of oxidative stress.
AB  - Previous studies have proved that activation of aldehyde dehydrogenase two
      (ALDH2) can attenuate oxidative stress through clearance of cytotoxic aldehydes,
      and can protect against cardiac, cerebral, and lung ischemia/reperfusion (I/R)
      injuries. In this study, we investigated the effects of the ALDH2 activator Alda
      1 on hepatic I/R injury. Partial warm ischemia was performed in the left and
      middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of
      reperfusion. Rats received either Alda-1 or vehicle by intravenous injection 30
      min before ischemia. Blood and tissue samples of the rats were collected after 6
      h reperfusion. Histological injury, proinflammatory cytokines, reactive oxygen
      species (ROS), cellular apoptosis, ALDH2 expression and activity, 4-hydroxy-trans
      2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. BRL-3A hepatocytes
      were subjected to hypoxia/reoxygenation (H/R). Cell viability, ROS, and
      mitochondrial membrane potential were determined. Pretreatment with Alda-1
      significantly alleviated I/R-induced elevations of alanine aminotransferase and
      aspartate amino transferase, and significantly blunted the pathological injury of
      the liver. Moreover, Alda-1 significantly inhibited ROS and proinflammatory
      cytokines production, 4-HNE and MDA accumulation, and apoptosis. Increased ALDH2
      activity was found after Alda-1 administration. No significant changes in ALDH2
      expression were observed after I/R. ROS was also higher in H/R cells than in
      control cells, which was aggravated upon treatment with 4-HNE, and reduced by
      Alda-1 treatment. Cell viability and mitochondrial membrane potential were
      inhibited in H/R cells, which was attenuated upon Alda-1 treatment. Activation of
      ALDH2 by Alda-1 attenuates hepatic I/R injury via clearance of cytotoxic
      aldehydes.

PMID- 29589773
TI  - Readiness to change for interprofessional collaboration in healthcare:
      Development and validation of a theory-based instrument.
AB  - This paper presents a study that aimed to develop and validate a theory-based
      instrument for the assessment of readiness to change for interprofessional
      collaboration in healthcare (IPC-TTM). The instrument was developed in the
      Persian language and tested in the Iranian context. Healthcare professionals from
      medical and nursing professions participated in the assessment of validity and
      reliability of the instrument. We conducted this psychometric study in two
      phases: First, the questionnaire was developed based on the transtheoretical
      model (TTM) through literature review and expert panel. Then, in the validation
      phase, we held three modified Delphi rounds to assess the content and face
      validity of the questionnaire. We used confirmatory factor analysis (CFA) to
      evaluate the fit of the questionnaire as applied to modified TTM. Reliability of
      the final instrument was tested by assessing the test-retest reliability of
      instrument items with Kappa coefficient. We also calculated the intraclass
      correlation coefficient (ICC) and Cronbach's alpha to assess the test-retest
      reliability and internal consistency of the instrument sub-scales. The initial
      item pool consisted of 30 items and three sub-scales (Attitude, Intention, and
      Action). The content validity of the questionnaire was confirmed with 17 items.
      Based on the CFA results two additional items were deleted to increase the fit of
      the model. The final instrument was confirmed with 15 items and three sub-scales.
      Reliability assessment on the 15-item instrument showed an acceptable test-retest
      reliability of the instrument items. ICC values for the Attitude, Intention, and
      Action sub-scales of the instrument were calculated as 0.82, 0.73, and 0.71,
      respectively. Moreover, Cronbach's alpha for the Attitude, Intention, and Action
      sub-scales were 0.85, 0.73, and 0.77, respectively. This study offers a new
      theory-based instrument to measure readiness to change for interprofessional
      collaboration in healthcare in the Iranian context. The questionnaire can be used
      for 'needs assessment' in developing tailored educational interventions and self
      assessments in interprofessional education studies.

PMID- 29589774
TI  - Solution space: Monitoring the dynamics of motor rehabilitation.
AB  - This article presents and discusses a perspective on the concept of "solution
      space" in physiotherapy. The model is illustrated with a subjective assessment of
      the way movements are performed and an objective quantification of the dynamics
      of the recovery process for a patient with a knee injury. Based on insights from
      the domain of human motor control, solution space is a key concept in our
      recovery model that explains the emergence of a variety of adaptive changes that
      may occur in the movement system recovering from an injury. The three dimensions
      that span the solution space are: (1) information and control processes; (2)
      time; and (3) degrees of freedom. Each dimension is discussed within the context
      of feasible physiotherapeutic assessments to identify and facilitate desirable
      behavioral patterns or bypass emerging but undesirable behavioral patterns that
      could impede both short- and long-term recovery. Central to this article is our
      view on the relationship between the recovery process and the three dimensions of
      the solution space, which determines the model's usefulness as a motor
      rehabilitation monitoring tool.

PMID- 29589775
TI  - Role of CYP2C19 genotype testing in clinical use of clopidogrel: is it really
      useful?
AB  - INTRODUCTION: P2Y12 inhibitors, including clopidogrel have become an integral
      part of treatment for patients receiving coronary stent placement as a result of
      stable coronary artery disease or acute coronary syndromes (ACS) and also for
      medically managed ACS patients. Areas covered: Clopidogrel efficacy can be
      significantly modified by polymorphism of CYP2C19 genotype (more than 25 allelic
      variants) involved in its metabolism that can adversely affect its anti-platelet
      activity. As a result, a substantial number of patients (20-30%) with ACS show an
      inadequate response to clopidogrel despite a standardized dosing regimen. Experts
      commentary: Currently, there is conflicting evidence in regards to the use of
      CYP2C19 genotyping to identify poor responders to clopidogrel in clinical
      practice. ACC/AHA guidelines do not recommend routine use of CYP2C19 in clinical
      practice, whereas Clinical Pharmacogenetics Implementation Consortium (CPIC)
      guidelines recommend its use to identify poor/intermediate metabolizers of
      Clopidogrel and suggest alternative P2Y12 inhibitors among ACS patients
      undergoing percutaneous coronary intervention. This review article will look at
      the literature evidence for the use of CYP2C19 genotyping in clinical practice.

PMID- 29589776
TI  - Inter-rater reliability of DartfishTM movement analysis software for measuring
      maximum flexion and extension at the hip and knee in older adults with
      osteoporosis and osteopenia.
AB  - Various methods are used to measure hip and knee joint motion angles; however,
      their use is often limited by cost or inability to measure dynamic movements. The
      assessment of movement patterns is clinically useful in individuals with
      osteoporosis (OP) and osteopenia (OPe) through its potential to optimize fracture
      risk assessment. This study evaluates the inter-rater reliability of using
      DartfishTM 2-D Motion Analysis Software to measure maximum flexion and extension
      angles at the hip and knee in individuals with OP or OPe while performing five
      tasks of the Safe Functional Motion test. Twelve participants were videotaped
      performing the pour, footwear, newspaper, sweep, and sit-to-floor tasks. Five
      raters used DartfishTM to analyze maximum flexion and extension angles at the hip
      and knee, and an intra-class correlation coefficients (ICC) and SEM were
      calculated for each measurement. In all five tasks, ICC and SEM values ranged
      from 0.23 to 0.95, and 1.75 to 11.54 degrees, respectively, with maximum knee
      flexion angles generally having higher ICC, and lower SEM point estimates. The
      results indicate that DartfishTM measurements of maximum knee flexion angles in
      uniplanar tasks demonstrate a moderate to excellent degree of inter-rater
      reliability, while measurements at the hip joint should be used with caution.
      Given that the results of this study display moderate to excellent reliability,
      they lay the groundwork for future research aimed at determining the validity of
      these measurements. Such research would help to further develop the base of
      evidence surrounding the usefulness of DartfishTM Motion Analysis in fracture
      risk analysis among individuals with OP.

PMID- 29589777
TI  - Mirror therapy and treadmill training for a patient with chronic stroke: A case
      report.
AB  - INTRODUCTION: A large proportion of patients with chronic stroke have permanent
      lower limb functional disability leading to reduced levels of independent
      mobility. Individually, both mirror therapy and treadmill training have been
      shown to improve aspects of lower limb functioning in patients with stroke. This
      case report examined whether a new combination of both interventions would lead
      to improvements in lower limb functional disability for a patient with chronic
      stroke. CASE DESCRIPTION: The participant was a 50-year-old female who had a left
      middle cerebral artery infarction (47 months' post stroke). Due to hemiparesis,
      she had lower limb motor impairment and gait deficits. INTERVENTION: The
      participant engaged in a combination of mirror therapy and treadmill training for
      30 minutes per day, 3 days per week, for 4 weeks. OUTCOMES: Modified Ashworth
      Scale, Fugl-Meyer Assessment-Lower Extremity and the 10 m Walk Test demonstrated
      clinically meaningful change. The 6 Minute Walk Test did not demonstrate
      meaningful change. DISCUSSION: The positive outcomes from this new combination
      therapy for this participant are encouraging given the relatively small dose of
      training and indicate the potential benefit of mirror therapy as an adjunct to
      treadmill training for enhancing lower limb muscle tone, motor function and
      walking velocity in patients with chronic stroke.

PMID- 29589778
TI  - Physiotherapy management of patients with chronic pelvic pain (CPP): A systematic
      review.
AB  - INTRODUCTION: Chronic pelvic pain (CPP) is a common pain condition. However,
      treatment remains challenging. Musculoskeletal findings are frequent; therefore
      physiotherapy might be helpful. The purpose of this review was to evaluate the
      current evidence on physiotherapy in patients with CPP (PROSPERO registration
      number CRD42016037516). METHODS: Six databases were searched and additional hand
      searches were performed. Two reviewers independently conducted the database
      search and selected studies using a two-step approach. The methodological quality
      was assessed applying the Critical Review Form - Quantitative Studies. RESULTS: A
      total of eight studies were included. Trigger point therapy was examined in four
      studies; two of which were randomized controlled trials. All studies indicate a
      significant change in pain measurement. The other four studies evaluated the
      effect of biofeedback, Thiele massage, Mensendieck somatocognitive therapy and
      aerobic exercises, whereas the last two were tested in controlled trials. All
      studies showed significant improvements in pain assessment. CONCLUSIONS: The
      evidence currently available is sparse with methodological flaws, making it
      difficult to recommend a specific physiotherapy option. There is an urgent need
      for high-quality randomized controlled trials to identify the most effective
      physiotherapy management strategy for patients with CPP.

PMID- 29589779
TI  - Telomere length is independently associated with age, oxidative biomarkers, and
      sport training in skeletal muscle of healthy adult males.
AB  - In skeletal muscle, which mainly contains postmitotic myonuclei, it has been
      suggested that telomere length remains roughly constant throughout adult life, or
      shortens in response to physiopathological conditions in muscle diseases or in
      the elderly. However, telomere length results from both the replicative history
      of a specific tissue and the exposure to environmental, DNA damage-related
      factors, therefore the predictive biological significance of telomere measures
      should combine the analysis of the various interactive factors. In the present
      study, we analysed any relationship between telomere length [mean and minimum
      terminal restriction fragment (TRF) length] chronological age, oxidative damage
      (4-HNE, protein carbonyls), catalase activity, and heat shock proteins expression
      (alphaB-crystallin, Hsp27, Hsp90) in semitendinous muscle biopsies of 26 healthy
      adult males between 20 and 50 years of age, also exploring the influence of
      regular exercise participation. The multiple linear regression analysis
      identified age, 4-HNE, catalase, and training status as significant independent
      variables associated with telomere length and jointly accounting for ~30-36% of
      interindividual variation in mean and/or minimum TRF length. No association has
      been identified between telomere length and protein carbonyl, alphaB-crystallin,
      Hsp27, and Hsp90, as well as between age and the variables related to stress
      response. Our results showed that skeletal muscle from healthy adults displays an
      age-dependent telomere attrition and that oxidised environment plays an age
      independent contribution, partially influenced by exercise training.

PMID- 29589780
TI  - What are private sector physiotherapists' perceptions regarding interprofessional
      and intraprofessional work for managing low back pain?
AB  - In the last decades, interactions between health professionals have mostly been
      discussed in the context of interprofessional teamwork where professionals work
      closely together and share a team identity. Comparatively, little work has been
      done to explore interactions that occur between professionals in contexts where
      traditionally formal structures have been less supporting the implementation of
      interprofessional teamwork, such as in the private healthcare sector. The
      objective of this study was to identify private sector physiotherapists'
      perceptions of interprofessional and intraprofessional work regarding
      interventions for adults with low back pain. This was a cross-sectional survey of
      327 randomly-selected physiotherapists. Data were analysed using descriptive
      statistics. A majority of physiotherapists reported positive effects of
      interprofessional work for their clients, themselves and their workplaces.
      Proximity of physiotherapists with other professionals, clinical workloads, and
      client's financial situation were perceived as important factors influencing the
      implementation of interprofessional work. Low back pain is a highly prevalent and
      disabling condition. The results of this study indicate that integrating
      interprofessional work in the management of low back pain in the private sector
      is warranted. Furthermore, the implementation of interprofessional work is viewed
      by practicing physiotherapists as dependent upon certain client-, professional-
      and organizational-level factors.

PMID- 29589781
TI  - Physicians' perspectives of pharmacist-physician collaboration in the United Arab
      Emirates: Findings from an exploratory study.
AB  - Interprofessional collaborative care has been shown to improve patient outcomes.
      Physicians' views on collaboration with pharmacists give an insight into what
      contributes to a well-functioning team. Little is known about these views from
      low and middle-income countries and nothing from the United Arab Emirates (UAE).
      The purpose of this study is to investigate physicians' opinions on collaborative
      relationships with community pharmacists in the UAE. Semi-structured individual
      interviews and group discussions are conducted with a purposive sample of
      physicians. Thematic analysis based on the framework approach is used to generate
      themes. A total of 53 physicians participated. Three themes about collaboration
      emerged: perceived benefits of collaboration, facilitators of collaboration and
      perceived barriers to collaboration. Perceived benefits include reducing the
      burden on physicians, having the pharmacist as an extra safety check within the
      system, having the pharmacist assist patients to manage their medications: coping
      with side effects, reducing drug waste and costs, and attaining professional and
      health-system gains. Perceived facilitators included awareness and trust
      building, professional role definition, pharmacists' access to patient records
      and effective communication. Perceived barriers included patient and physician
      acceptance, logistic and financial issues and perceived pharmacist competence.
      This study has, for the first time, provided useful information to inform the
      future development of pharmacist-physician collaboration in the UAE and other
      countries with similar healthcare systems.

PMID- 29589782
TI  - Immediate preoperative outcomes of pain neuroscience education for patients
      undergoing total knee arthroplasty: A case series.
AB  - BACKGROUND: Standard preoperative education for total knee arthroplasty (TKA) has
      been shown to have no effect on postoperative outcomes. This may be because such
      education programs fail to educate patients about pain. Pain neuroscience
      education (PNE) focuses on teaching people more about pain from a neurobiological
      and neurophysiological perspective. DESIGN AND SETTING: Case Series. AIM: To
      determine the immediate effects, if any, of providing PNE before TKA surgery on
      patient self-report measures. PARTICIPANTS: Twelve patients (female = 10) prior
      to TKA for knee osteoarthritis (OA). INTERVENTION: Preoperative educational
      session by a physical therapist on the neuroscience of pain, accompanied by an
      evidence-based booklet. MAIN OUTCOME MEASURES: Comparison of pre- and post-PNE
      self-report measures on knee pain (NPRS), Pain Catastrophization Scale (PCS),
      fear of movement (TSK), and beliefs about TKA; as well as three physical
      performance measures - knee flexion active range of motion, 40 m self-paced walk,
      and pressure pain threshold (PPT). RESULTS: Immediately following the PNE,
      patients had statistically significant lower TSK scores, increased PPT, and
      improved beliefs about their upcoming surgery. There were no significant changes
      in knee pain, function, or flexion active range of motion. CONCLUSIONS: Results
      appear to suggest that immediately after PNE, patients scheduled for TKA had
      statistically significant changes in fear of movement, decreased sensitivity to
      pain and positive shifts in their beliefs about their future knee surgery. Larger
      trials with control/comparison groups are warranted to determine the true effects
      of preoperative PNE for patients about to undergo TKA.

PMID- 29589783
TI  - Spectrally Resolved Ultraviolet (UV) Absorption Cross-Sections of Alkali
      Hydroxides and Chlorides Measured in Hot Flue Gases.
AB  - Spectrally resolved ultraviolet (UV) absorption cross-sections of gas-phase
      sodium chloride (NaCl), potassium hydroxide (KOH), and sodium hydroxide (NaOH)
      were measured, for the first time, in hot flue gases at different temperatures.
      Homogenous gas-phase NaCl, KCl (potassium chloride), NaOH, and KOH at
      temperatures 1200 K, 1400 K, 1600 K, and 1850 K were prepared in the post-flame
      zone of laminar flames by seeding nebulized droplets out of aqueous solution of
      corresponding alkali species. The amount of droplets seeded into the flame was
      kept constant, so the relative concentration of different alkali species can be
      derived. The broadband UV absorption cross-section of KCl vapor reported by
      Leffler et al. was adopted to derive the absorption cross-section curves of NaCl,
      NaOH, and KOH with the corresponding measured spectrally resolved absorbance
      spectra. No significant changes in the spectral structures in the absorption
      cross-sections were found as the temperature varied between 1200 K and 1850 K,
      except for NaOH at around 320 nm. The difference between the absorption spectral
      curves of alkali chlorides and hydroxides is significant at wavelengths above 300
      nm, which thus can be used to distinguish and obtain the concentrations of alkali
      chlorides and hydroxides in the broadband UV absorption measurements.

PMID- 29589784
TI  - Short-Term Complications, Reoperations, and Radiographic Outcomes of a New Fixed
      Bearing Total Ankle Arthroplasty.
AB  - BACKGROUND: With the increasing use of total ankle arthroplasty (TAA), new
      implants with varied configurations are being developed every year. This study
      aimed to assess the early complications, reoperations, and radiographic and
      clinical outcomes of the Infinity TAA. To date, clinical results of this novel
      implant have not been published. METHODS: A retrospective analysis of 64
      consecutive ankles that underwent a primary Infinity TAA from July 2014 to April
      2016 was performed. Patients had an average follow-up of 24.5 (range, 18-39)
      months. Medical records were reviewed to determine the incidence of
      complications, reoperations, and revisions. Radiographic outcomes included
      preoperative and postoperative tibiotalar alignment, tibial implant positioning,
      the presence of periprosthetic radiolucency and cysts, and evidence of subsidence
      or loosening. Additionally, patient-reported outcomes were analyzed with the Foot
      and Ankle Outcome Score (FAOS). RESULTS: Survivorship of the implant was 95.3%.
      Fourteen ankles (21.8%) presented a total of 17 complications. A total of 12
      reoperations were necessary in 11 ankles (17.1%). Revision surgery was indicated
      for 3 ankles (4.7%) as a result of subsidence of the implant. Tibiotalar coronal
      deformity was significantly improved after surgery ( P < .0001) and maintained
      during latest follow-up ( P = .81). Periprosthetic radiolucent lines were
      observed around the tibial component in 20 ankles (31%) and around the talar
      component in 2 ankles (3.1%). A tibial cyst was observed in 1 ankle (1.5%).
      Outcome scores were significantly improved for all FAOS components analyzed ( P <
      .0001), from 39.0 to 83.3 for pain, from 34.0 to 65.2 for symptoms, from 52.3 to
      87.5 for activities of daily living, and from 15.7 to 64.2 for quality of life.
      CONCLUSION: Most complications observed in the study were minor and successfully
      treated with a single reoperation procedure or nonoperatively. Failures and
      radiographic abnormalities were most commonly related to the tibial implant.
      Further studies with longer follow-up are needed to evaluate the survivorship of
      the tibial implant in the long term. LEVEL OF EVIDENCE: Level IV, retrospective
      case series.

PMID- 29589785
TI  - Correlation of Clinical Evaluation and Radiographic Hindfoot Alignment in Stage
      II Adult-Acquired Flatfoot Deformity.
AB  - BACKGROUND: Previous work has demonstrated that the amount of radiographic
      hindfoot correction required at the time of adult-acquired flatfoot deformity
      (AAFD) operative treatment can be predicted by the amount of radiographic
      deformity present before surgery. Successful outcomes after reconstruction are
      closely correlated with hindfoot valgus correction. However, it is not clear if
      differences exist between clinical and radiographic assessment of hindfoot
      valgus. The purpose of this study was to evaluate the correlation between
      radiographic and clinical evaluation of hindfoot alignment in patients with stage
      II AAFD. METHODS: Twenty-nine patients (30 feet) with stage II AAFD, 17 men and
      12 women, mean age of 51 (range, 20-71) years, were prospectively recruited. In a
      controlled and standardized fashion, bilateral weightbearing radiographic
      hindfoot alignment views were taken. Radiographic parameters were measured by 2
      blinded and independent readers: hindfoot alignment angle (HAA) and hindfoot
      moment arm (HMA). Clinical photographs of hindfoot alignment were taken in 3
      different vertical camera angulations (0, 20, and 40 degrees). Pictures were
      assessed by the same readers for standing tibiocalcaneal angle (STCA) and resting
      calcaneal stance position (RCSP). Intra- and interobserver reliability were
      assessed by Pearson/Spearman's and intraclass correlation coefficient (ICC),
      respectively. Relationship between clinical and radiographic hindfoot alignment
      was evaluated by a linear regression model. Comparison between the different
      angles (RCSP, STCA, and HAA) was performed using the Wilcoxon rank-sum test. P
      values of less than .05 were considered significant. RESULTS: We found overall
      almost perfect intraobserver (range, 0.91-0.99) and interobserver reliability
      (range, 0.74-0.98) for all measures. Mean value and confidence interval (CI) for
      RCSP and STCA were 10.8 degrees (CI, 10.1-11.5) and 12.6 degrees (CI, 11.7-13.4),
      respectively. The position of the camera did not influence readings of clinical
      alignment ( P > .05). The mean HMA was 18.7 mm (CI, 16.3-21.1 mm), and the mean
      HAA was 23.5 degrees (CI, 21.1-26.0). Clinical and radiographic hindfoot
      alignment were found to significantly correlate ( P < .05). However, the
      radiographic HAA demonstrated increased valgus compared to both clinical
      alignment measurements, with a mean difference of 12.8 degrees from the RCSP (CI,
      11.0-14.5, P < .0001) and 11.0 degrees from the STCA (CI, 9.2-12.8, P < .0001).
      CONCLUSION: We found significant correlation between radiographic and clinical
      hindfoot alignment in patients with stage II AAFD. However, radiographic
      measurements of HAA demonstrated significantly more pronounced valgus alignment
      than the clinical evaluation. The results of our study suggest that clinical
      evaluation of hindfoot alignment in patients with AAFD potentially underestimates
      the bony valgus deformity. One should consider these findings when using clinical
      evaluation in the treatment algorithm of flatfoot patients. LEVEL OF EVIDENCE:
      Level II, prospective comparative study.

PMID- 29589787
TI  - Implementation of motor learning principles in physical therapy practice: Survey
      of physical therapists' perceptions and reported implementation.
AB  - INTRODUCTION: The field of motor learning (ML) plays a pivotal role in physical
      therapy (PT), and its implementation has been shown to improve intervention
      outcomes. The objective of this study was to assess physical therapists' ML
      related self-efficacy, self-reported implementation, and environmental workplace
      factors. An additional aim was to report the psychometric properties of a
      questionnaire that was developed to assess the above-mentioned constructs.
      METHODS: An observational, cross-sectional survey was completed by 289 physical
      therapists (average age: 38.7 (9.7), with 11.3 (9.7) years of experience and 74%
      female). Construct validity, internal consistency, and test-retest reliability
      were tested. The main outcome measures were the scores of the three scales of the
      questionnaire, referring to self-efficacy in ML, implementation of ML principles,
      and workplace environment features. RESULTS: The questionnaire had sound
      psychometric qualities. Respondents perceived ML as an integral part of PT. ML
      related self-efficacy and implementation of ML principles were moderate (2.95/5
      (0.7) and 3.04/5(0.8), respectively). PT practice had a significant effect on ML
      related self-efficacy (p = 0.035) and implementation (p = 0.0031). Respondents
      who had undergone ML training in their graduate program reported higher ML
      related self-efficacy (p = 0.007). Respondents who had postgraduate training in
      ML reported significantly more extensive implementation (p = 0.024). Lack of
      knowledge and lack of time were perceived as the major barriers to
      implementation. CONCLUSIONS: Level of self-efficacy might be insufficient to
      support the systematic implementation of ML principles in practice. Addressing
      impeding individual- and organizational-level factors might facilitate ML self
      efficacy and implementation. Postgraduate education facilitates ML
      implementation.

PMID- 29589788
TI  - Emotional valence impacts lexical activation and inhibition differently in aging:
      an emotional Hayling task investigation.
AB  - BACKGROUND: Aging is characterized by cognitive changes such as a potential
      inhibition deficit. However, growing evidence shows that positive valence stimuli
      enhance performances in older adults to a greater degree than in younger adults.
      The aim of the present study was to investigate the effect of the emotional
      valence of words on lexical activation and inhibition in aging by using a new
      Emotional Hayling Task. METHODS: Thirty-eight younger adults (mean age = 20.11
      years) and 38 older adults (mean age = 66.47 years) performed a computerized
      Emotional Hayling task. Participants had to choose the correct (initiation part)
      or incorrect (inhibition part) final words of highly predictable incomplete
      sentences. Final words had a negative or positive emotional valence and were
      paired for reaction time comparison with neutral words. RESULTS: Response times
      were faster in younger adults than in older adults in both the initiation and the
      inhibition parts. In addition, response times indicated that older adults
      initiated more slowly negative than neutral words while no differences emerged in
      inhibition. No differences were obtained between negative and neutral words in
      younger adults. Response times showed faster initiation and inhibition for
      positive than for neutral words in both age groups. CONCLUSION: These data are
      consistent with previous findings suggesting a disengagement from the processing
      of negative versus neutral words in older adults when compared with younger
      adults. A possible explanation is that activation of negative words in the mental
      lexicon is weaker in older than in younger adults. Conversely, the positive
      valence of words seems to enhance both activation and inhibition processes in
      both young and older adults. These findings suggest that positive stimuli can
      improve performance.

PMID- 29589789
TI  - Trial-by-trial modulations in the orienting of attention elicited by gaze and
      arrow cues.
AB  - Recent findings suggested that the orienting of attention towards gazed at
      locations (i.e., the gaze cueing effect) could result from the conflict emerging
      in incongruent trials between the spatial information conveyed by gaze direction
      and the target spatial position. In two experiments, we assessed this hypothesis
      by investigating whether this effect is influenced by the same trial-by-trial
      modulations that are reported in a spatial conflict task, i.e., the Simon task.
      In Experiment 1, we compared the trial-by-trial modulations emerging in the Simon
      task with those emerging in a gaze cueing task, while in Experiment 2, we
      compared gaze and arrows cues. Trial-by-trial modulations were evident in both
      tasks. In the Simon task, correspondence sequence affected both corresponding and
      noncorresponding responses, this resulting in a larger Simon effect when the
      preceding trial was corresponding and an absent effect when the preceding trial
      was noncorresponding. Differently, in the gaze cueing task, congruence sequence
      affected only congruent responses with faster responses when the preceding trial
      was congruent compared to when it was incongruent, resulting in a larger gaze
      cuing effect when the preceding trial was congruent. Same results were evident
      with nonpredictive arrow cues. These findings speak against a spatial conflict
      account.

PMID- 29589790
TI  - Object attraction effects during subject-verb agreement in Persian.
AB  - Subject-verb agreement provides insight into how grammatical and semantic
      features interact during sentence production, and prior studies have found
      attraction errors when an intervening local noun is grammatically part of the
      subject. Two major types of theories have emerged from these studies: control
      based and competition-based. The current study used an subject-object-verb
      language with optional subject-verb agreement, Persian, to test the competition
      based hypothesis that intervening object nouns may also cause attraction effects,
      even though objects are not part of the syntactic relationship between the
      subject and verb. Our results, which did not require speakers to make grammatical
      errors, show that objects can be attractors for agreement, but this effect
      appears to be dependent on the type of plural marker on the object. These results
      support competition-based theories of agreement production, in which agreement
      may be influenced by attractors that are outside the scope of the subject-verb
      relationship.

PMID- 29589791
TI  - Evidence for selective adjustments of inhibitory control in a variant of the stop
      signal task.
AB  - The ability to inhibit actions inappropriate for the context is essential for
      meeting the shifting demands of complex environments. The stop signal task (SST)
      has been used in many previous studies to examine the interactions between go and
      stop responses in a cognitively demanding task involving attention, conflict
      resolution, and motor plan selection. The current study uses a variant of the
      SST, in which the continue signal instructs participants to proceed with the go
      response they were preparing. Reaction times (RTs) on continue trials were
      bimodally distributed, suggesting that an aspect of inhibition was involved in at
      least some of the trials. We investigated whether the cognitive processes
      delaying the generation of a behavioural response on continue trials are the same
      as for stop trials. We found improvement of stop signal reaction times (SSRTs)
      following stop trials, but the decrease in continue signal reaction times (CSRTs)
      was not significant. No improvement in either SSRT or CSRT was found following
      continue trials, suggesting that activation of the processes delaying the
      response on continue trials is insufficient to drive subsequent adjustments in
      SSRT or CSRT. In addition, go RTs only slowed following stop trials. These
      effects may suggest the presence of a selective learning process, which requires
      that the initial inhibition captured by SSRT and CSRT be combined with
      recognition of the stop signal specifically to affect subsequent performance.

PMID- 29589786
TI  - A randomized controlled trial comparing the Thompson hemiarthroplasty with the
      Exeter polished tapered stem and Unitrax modular head in the treatment of
      displaced intracapsular fractures of the hip.
AB  - Aims: This study aimed to compare the change in health-related quality of life of
      patients receiving a traditional cemented monoblock Thompson hemiarthroplasty
      compared with a modern cemented modular polished-taper stemmed hemiarthroplasty
      for displaced intracapsular hip fractures. Patients and Methods: This was a
      pragmatic, multicentre, multisurgeon, two-arm, parallel group, randomized
      standard-of-care controlled trial. It was embedded within the WHiTE Comprehensive
      Cohort Study. The sample size was 964 patients. The setting was five National
      Health Service Trauma Hospitals in England. A total of 964 patients over 60 years
      of age who required hemiarthroplasty of the hip between February 2015 and March
      2016 were included. A standardized measure of health outcome, the EuroQol (EQ-5D
      5L) questionnaire, was carried out on admission and at four months following the
      operation. Results: Of the 964 patients enrolled, 482 died or were lost to follow
      up (50%). No significant differences were noted in EQ-5D between groups, with a
      mean difference at four months of 0.037 in favour of the Exeter/Unitrax implant
      (95% confidence interval (CI) 0.014 to 0.087, p = 0.156), rising to 0.045 (95% CI
      0.007 to 0.098, p = 0.09) when patients who died were excluded. The minimum
      clinically important difference for EQ-5D-5L used in this study is 0.08,
      therefore any benefit between implants is unlikely to be noticeable to the
      patient. There was no difference in mortality or mobility score. Conclusion:
      Allowing for the high rate of loss to follow-up, the use of the traditional
      Thompson hemiarthroplasty in the treatment of the displaced intracapsular hip
      fracture shows no difference in health outcome when compared with a modern
      cemented hemiarthroplasty. Cite this article: Bone Joint J 2018;100-B:352-60.

PMID- 29589792
TI  - Patient controlled analgesia: The impact of an 8 versus 10 minute lockout
      interval in postoperative patients.
AB  - The purpose of this study was to compare the level of pain control achieved with
      8 versus 10 minute lockout intervals in adult patients who received patient
      controlled analgesia (PCA) within 24 hours of surgery. There was no difference in
      pain in the first 72 hours between the 8 minute and 10 minutes group.
      Additionally, there was no difference in time to first PCA regimen change or a
      composite outcome of adverse events.

PMID- 29589793
TI  - Young Africans' social representations of sexual abuse of power in their HIV
      related creative narratives, 2005-2014: cultural scripts and applied
      possibilities.
AB  - The sexual abuse of power is a form of sexual coercion in which individuals -
      typically male - use their positions of authority to obtain sex. We analysed
      social representations of sexual abuse of power in a sample of 1,446 narratives
      about HIV written by young Africans between 2005 and 2014. The narratives were
      prepared at five different points in time (2005, 2008, 2011, 2013 and 2014) by
      authors aged 10-24 in urban and rural areas of Swaziland, Kenya, South-East
      Nigeria, Burkina Faso and Senegal. We combined three analytical approaches:
      descriptive statistics of quantifiable characteristics of the narratives,
      thematic data analysis and a narrative-based approach. Analysis revealed two
      underlying cultural scripts describing the sexual abuse of power between (a)
      teachers and female students, and (b) male employers and domestic workers. Cross
      national variation was evident in the emphasis authors placed on socio-contextual
      inequalities, particularly poverty, and on individual level blame. While a
      minority of Nigerian and Burkinabe authors depicted female characters creatively
      exercising agency and avoiding unwanted sex, overall there was little critique of
      underlying assumptions of male sexual entitlement and female responsibility for
      controlling male sexuality in the context of unequal control of resources. We
      outline recommendations for strategies to deconstruct these harmful scripts.

PMID- 29589794
TI  - Adding a Parent to the Brain Tumor Team: Evaluating a Peer Support Intervention
      for Parents of Children With Brain Tumors.
AB  - Childhood brain tumors often present profound challenges to patients and
      families. To address these challenges, the California Chapter of the Pediatric
      Brain Tumor Foundation provides hospital-based support services to parents of
      children with brain tumors from a Veteran Parent (VP). This mixed-methods, cross
      sectional study was designed to evaluate the effectiveness of the intervention
      using validated tools to compare parental resilience and impact of illness on the
      family between parents who met with the VP and those who did not. Two-tailed t
      tests assessed significant differences in scores on the PedsQL Family Impact
      module and Connor-Davidson Resilience Scale (CD-RISC-25). Additional qualitative
      data gleaned from focus groups with stakeholders (health care providers and
      parents) were analyzed using key constructs of social support theory with
      Atlas.ti. Although there were no significant differences in overall scores on the
      PedsQL Family Impact module or CD-RISC-25 between groups, parents in the
      intervention group scored better on items related to handling difficult decisions
      and painful feelings. Overarching themes emerged from focus groups around
      participants' experiences with the program and included informational and
      emotional support, peer parent relatedness, changed outlook, and empowerment.
      Results reveal the impact of peer parent support and need for emotional and
      instrumental support.

PMID- 29589795
TI  - Ethical considerations with regard to adolescent consent in the perioperative
      setting: Talking points for anaesthetic practitioners.
AB  - The legal and ethical issues surrounding the care of children and young people in
      the perioperative setting are often vague and an anaesthetic practitioner could
      find themselves inadequately prepared for any issues that may arise. This paper
      details the case of an adolescent who withdrew her consent to surgery whilst in
      the anaesthetic room. It raises questions about Gillick Competency and whether
      the use of restraint is ever justified.

PMID- 29589796
TI  - Child-Mother Agreement on Experiences of School Bullying Involvement in Children
      With ADHD.
AB  - OBJECTIVE: To examine the levels of agreement between the reports of 452 children
      and their mothers on children's experiences of bullying involvement at school and
      investigate the factors influencing the levels of agreement in children with
      ADHD. METHOD: The levels of agreement between children's and mothers' reports
      were examined. The influence of age, sex, ADHD symptoms, and psychiatric
      comorbidities on the levels of agreement was also examined. RESULTS: The results
      indicated low agreement on the experiences of bullying involvement in child
      mother ADHD dyads. Age and hyperactivity-impulsivity, oppositional, depressive,
      and anxiety symptoms significantly influenced the levels of agreement on the
      victimization of physical bullying. Age significantly influenced the levels of
      agreement on the perpetration of physical bullying. CONCLUSION: Multiple sources
      of information are required when clinicians assess the experiences of bullying
      involvement at school in children with ADHD. The factors influencing the levels
      of agreement should be considered.

PMID- 29589797
TI  - ADHD Endophenotypes in Caribbean Families.
AB  - OBJECTIVE: The aim of this study is to contrast the genetics of
      neuropsychological tasks in individuals from nuclear families clustering ADHD in
      a Caribbean community. METHOD: We recruited and clinically characterized 408
      individuals using an extensive battery of neuropsychological tasks. The genetic
      variance underpinning these tasks was estimated by heritability. A predictive
      framework for ADHD diagnosis was derived using these tasks. RESULTS: We found
      that individuals with ADHD differed from controls in tasks of mental control,
      visuospatial ability, visuoverbal memory, phonological and verbal fluency, verbal
      and semantic fluency, cognitive flexibility, and cognitive ability. Among them,
      tasks of mental control, visuoverbal memory, phonological fluency, semantic
      verbal fluency, and intelligence had a significant heritability. A predictive
      model of ADHD diagnosis using these endophenotypes yields remarkable
      classification rate, sensitivity, specificity, and precision values (above 80%).
      CONCLUSION: We have dissected new cognitive endophenotypes in ADHD that can be
      suitable to assess the neurobiological and genetic basis of ADHD.

PMID- 29589799
TI  - Lesbians' experiences and attitudes towards parenthood in Greece.
AB  - Same-sex parenthood is controversial subject. In this paper, we provide insights
      into the attitudes and experiences of self-reported lesbians regarding parenthood
      or the prospect of becoming a parent in the current Greek social and cultural
      context. In Greece, lesbians are not allowed access to in vitro fertilisation
      (IVF), while a solitary ('single') woman is allowed access for medical reasons.
      Fifty-nine (59) semi-structured in-depth interviews were conducted with women.
      What emerged from our data was a clear trend for participants to wish to have
      their own biological children based mostly on the belief that pregnancy would
      lead to a sense of self-completeness and/or fulfilment. Women also reported the
      negative impact of prejudice and social oppression on their reproductive
      autonomy. Interviewees reported that their reproductive choices were negatively
      influenced by their family and the wider socio-cultural environment. Even within
      a semi-permissive legal framework, impaired social acceptance of lesbian
      parenthood prohibits lesbians from becoming mothers. A major reason responsible
      for the positive attitude of most participants to shared biological motherhood
      was an altruistic attitude towards their partners.

PMID- 29589798
TI  - A latent class analysis of substance use and culture among gay, bisexual and
      other men who have sex with men.
AB  - Assessments of gay and bisexual men's substance use often obscures salient
      sociocultural and identity-related experiences related to how they use drugs.
      Latent class analysis was used to examine how patterns of substance use represent
      the social, economic and identity-related experiences of this population.
      Participants were sexually active gay and bisexual men (including other men who
      have sex with men), aged >= 16 years, living in Metro Vancouver (n = 774). LCA
      indicators included all substances used in the past six months self-reported by
      more than 30 men. Model selection was made with consideration to model parsimony,
      interpretability and optimisation of statistical criteria. Multinomial regression
      identified factors associated with class membership. A six-class solution was
      identified representing: 'assorted drug use' (4.5%); 'club drug use' (9.5%);
      'street drug use' (12.1%); 'sex drug use' (11.4%); 'conventional drug use' (i.e.
      tobacco, alcohol, marijuana; 25.9%); and 'limited drug use' (36.7%). Factors
      associated with class membership included age, sexual orientation, annual income,
      occupation, income from drug sales, housing stability, group sex event
      participation, gay bars/clubs attendance, sensation seeking and escape
      motivation. These results highlight the need for programmes and policies that
      seek to lessen social disparities and account for social distinctions among this
      population.

PMID- 29589800
TI  - TeleMental Health: Standards, Reimbursement, and Interstate Practice [Formula:
      see text].
AB  - BACKGROUND: TeleMental Health (TMH) is gaining widespread acceptance in the
      United States. OBJECTIVE: Summarize current evidence regarding TMH risks and
      benefits, standards of care, practice guidelines, reimbursement, and interstate
      practice issues pertinent to psychiatric nurses and consumers. DESIGN: A targeted
      review of literature, current practice, and TMH websites was generated using the
      following key search words: clinical outcomes, practice guidelines, regulations,
      interstate practice, and reimbursement for TMH. A search of government and
      professional organization websites and a literature review of PubMed and
      PsychINFO databases was limited to the past 15 years. RESULTS: Studies
      demonstrate TMH services are equal in efficacy to that provided in face-to-face
      encounters and preferred by some populations. Current TMH practice guidelines,
      reimbursement, and regulatory issues are reviewed. CONCLUSIONS: Providers,
      including psychiatric advanced practice registered nurses, can use TMH to
      effectively address the growing need for mental health services, although
      regulatory, licensure, and clinical issues must be addressed prior to offering
      TMH services.

PMID- 29589801
TI  - Psychometric properties of the pathological dissociation measures among Chinese -
      a pilot study using online methods.
AB  - PURPOSE: Pathological dissociation (PD) is an easily overlooked phenomenon in the
      mental health field. Standardized assessment is important for identifying
      dissociative symptoms and disorders. However, the use of PD measures in Chinese
      cultures needs investigation. This pilot study investigated the psychometric
      properties of three PD measures among Hong Kong Chinese. METHODS: The
      psychometric properties of the Dissociative Experiences Scale-Taxon, the 5-item
      Somatoform Dissociation Questionnaire, and the Self-Report Version of the
      Dissociative Disorders Interview Schedule (SR-DDIS) were evaluated using online
      methods in Hong Kong. RESULTS: The PD measures exhibited adequate to excellent
      internal consistency. The PD measures were negatively related to family support
      and can discriminate between participants with and without self-reported
      childhood abuse. There was excellent agreement between the online SR-DDIS results
      and the clinical diagnoses for presence of any dissociative disorder (DD) versus
      no DD. The DDs group scored significantly higher on PD measures than the
      depression group and the college student group. DISCUSSION: The initial findings
      suggest that PD can be assessed online in Hong Kong. Further investigation is
      necessary.

PMID- 29589802
TI  - The dependence of broadband ultrasound attenuation on phase interference in thin
      plates of variable thickness and curvature: a comparison of experimental
      measurement and computer simulation.
AB  - The measurement of broadband ultrasound attenuation describes the linear increase
      in ultrasound attenuation with frequency (dB/MHz); this is generally performed at
      the calcaneus, consisting of a high proportion of metabolically active cancellous
      bone. Although broadband ultrasound attenuation is not routinely implemented
      within clinical management since it cannot provide a reliable estimation of bone
      mineral density and hence clinical definition of osteopenia and osteoporosis, it
      offers a reliable means to predict osteoporotic fracture risk. One of the
      potential factors that can influence the accuracy of broadband ultrasound
      attenuation measurement is the effect of cortical end plates. This study aimed to
      explore this, performing a comparison of experimental study and computer
      simulation prediction. A total of three categories of thin discs were three
      dimensional (3D) printed to replicate cortical shells of (1) variable constant
      thickness (planar), (2) variable constant thickness (curved), and (3) variable
      thickness. A through-transmission technique was used, where two single-element,
      unfocused, 1 MHz broadband transducers, as utilised clinically, were positioned
      coaxially in a cylindrical holder and immersed in water. Both quantitative and
      qualitative analyses demonstrated that broadband ultrasound attenuation
      measurements of the 'planar' and 'curved' discs were not statistically different
      (p-values > 0.01). A cyclic relationship between broadband ultrasound attenuation
      and disc thickness was observed; this was replicated within a computer simulation
      of phase interference created by a double-reflection echo within each disc (R2 =
      97.0%). Variable-thickness discs provided broadband ultrasound attenuation
      measurements ranging between 31.6 +/- 0.1 and 40.60 +/- 0.1 dB/MHz. Again
      applying the double-reflection echo simulation, a high level of agreement between
      experimental and simulation was recorded (R2 = 93.4%). This study indicates that
      the cortical end plate can significantly affect the broadband ultrasound
      attenuation measurement of cancellous bone as a result of phase interference and,
      therefore, warrants further investigation to minimise its effect on clinical
      assessment.

PMID- 29589803
TI  - Psychometric Evaluation of the Symptoms of Dementia Screener (SDS) in a Geriatric
      Primary Care Population.
AB  - OBJECTIVES: The Symptoms of Dementia Screener (SDS) is an 11-item scale developed
      to screen for cognitive impairment. We aim to evaluate the psychometric
      properties of the SDS for use in primary care. METHODS: We analyzed data from 192
      patients: 25 not impaired, 42 with mild cognitive impairment (MCI), and 125 with
      dementia. Cronbach's reliability, convergent validity, and clinical utility were
      examined. The SDS was investigated at the item level using binary two-parameter
      model item response theory (IRT) techniques. RESULTS: The SDS demonstrated good
      reliability (11 items; alpha = .74). We found negative correlations between SDS
      and the Mattis DRS-2 (r = -.523, p < .01). Receiver operating characteristic
      (ROC) curves demonstrated acceptable clinical utility for detecting MCI and
      dementia with sensitivities and specificities of 83% and 52% for MCI; 78.4% and
      84% for dementia, and 91% and 52% for any impairment. IRT analyses revealed 10
      out of 11 items were moderately to very highly related to underlying latent
      factors of impairment. CONCLUSIONS: The SDS demonstrates good psychometric
      properties and is useful for detecting cognitive impairment in primary care
      settings. CLINICAL IMPLICATIONS: The SDS is an effective screening tool that does
      not require special training for its use in primary care. A positive screen
      indicates a need for further cognitive testing.

PMID- 29589804
TI  - Age-dependent physiological changes, medicines and sex-influenced types of falls.
AB  - : Background/Study context: We investigated various parameters related to falls
      including age-dependent physiological changes, regular medicine use and different
      types of falls experienced. There is a lack of research investigating the impact
      of health status, sex, polypharmacy and ageing on different types of falls such
      as unspecified fall on the same level, mechanical fall on the same level relating
      to slipping, tripping or loosing balance, fall from a chair, vehicle and fall as
      a result of syncope, fall from steps or stairs and fall from the height. METHODS:
      The study included a random sample of 250 older patients, which comprised 10% of
      the total number of patients (n = 2,492), admitted to a large-scale academic
      hospital following a fall. Patients' medicine and illness history, types of
      falls, liver, renal and sensory function were collected. Univariate analysis was
      used to examine associations between the type of fall and explanatory variables,
      followed by multinominal logistic regression analysis. RESULTS: There was a
      significant association between the type of fall and sex, p = 0.01, and between
      the type of fall and regular medicine use, p = 0.002. The multinominal logistic
      regression analysis revealed that the full model, which considered all
      explanatory variables together, was statistically significant, p < 0.001. The
      strongest predictor of all types of falls except 'fall from the height' was
      female sex followed by the regular medicine use. CONCLUSION: This study
      identified predictors for various types of falls in older people; the strongest
      predictor being a female sex followed by regular medicine use. Based on these
      findings, the medicine prescribing practice in this older population must be
      carefully reviewed.

PMID- 29589805
TI  - Hyaluronan impairs the barrier integrity of brain microvascular endothelial cells
      through a CD44-dependent pathway.
AB  - Hyaluronan (HA) constitutes the most abundant extracellular matrix component
      during brain development, only to become a minor component rapidly after birth
      and in adulthood to remain in specified regions. HA signaling has been associated
      with several neurological disorders, yet the impact of HA signaling at the blood
      brain barrier (BBB) function remains undocumented. In this study, we investigated
      the impact of HA on BBB properties using human-induced pluripotent stem cell
      (iPSC) -derived and primary human and rat BMECs. The impact of HA signaling on
      developmental and mature BMECs was assessed by measuring changes in TEER,
      permeability, BMECs markers (GLUT1, tight junction proteins, P-gp) expression and
      localization, CD44 expression and hyaluronan levels. In general, HA treatment
      decreased barrier function and reduced P-gp activity with effects being more
      prominent upon treatment with oligomeric forms of HA (oHA). Such effects were
      exacerbated when applied during BMEC differentiation phase (considered as
      developmental BBB). We noted a hyaluronidase activity as well as an increase in
      CD44 expression during prolonged oxygen-glucose deprivation stress. Inhibition of
      HA signaling by antibody blockade of CD44 abrogated the detrimental effects of HA
      treatment. These results suggest the importance of HA signaling through CD44 on
      BBB properties.

PMID- 29589806
TI  - How physiotherapists perceive, interpret, and respond to the ethical dimensions
      of practice: A qualitative study.
AB  - The profile and reach of physiotherapy has expanded in areas of extended scope of
      practice, and broader engagement with population needs beyond the individual
      treatment encounter. These changes raise increasingly complex ethical challenges
      evidenced by growth in physiotherapy-based ethics studies and discussions. This
      paper examines how a broad cross section of Australian physiotherapists perceive,
      interpret, and respond to ethical challenges in their work contexts and how
      professional codes of conduct are used in their practice. Using an interpretive
      qualitative methodology, purposive sampling of 88 members of national clinical
      special interest groups were recruited for focus group discussions. Narrative
      based and thematic data analysis identified ethical challenges as emerging from
      specific clinical contexts, and influenced by health organizations, funding
      policies, workplace relationships, and individually held perspectives. Five
      themes were developed to represent these findings: (1) the working environment,
      (2) balancing diverse needs and expectation, (3) defining ethics, (4) striving to
      act ethically, and (5) talking about ethics. The results portray a diverse and
      complex ethical landscape where therapists encounter and grapple with ethical
      questions emerging from the impact of funding models and policies affecting
      clinical work, expanding boundaries and scope of practice and changing
      professional roles and relationships. Codes of conduct were described as
      foundational ethical knowledge but not always helpful for "in the moment" ethical
      decision-making. Based on this research, we suggest how codes of conduct,
      educators, and professional associations could cultivate and nurture ethics
      capability in physiotherapy practitioners for these contemporary challenges.

PMID- 29589807
TI  - The Effect of Vaccine Literacy on Parental Trust and Intention to Vaccinate after
      a Major Vaccine Scandal.
AB  - Health literacy, and more specifically vaccine literacy, might be an important
      factor in reducing the negative effects of exposure to misleading reports on
      vaccination. This study explores the association between vaccine literacy and
      vaccination-related outcomes after misleading reports on a scandal concerning
      locally produced childhood vaccines had emerged in 2016 in China. Data for this
      study came from a cross-sectional survey, which was conducted in April 2016 in
      Hangzhou, China. Data were collected in kindergartens and community health
      centers among parents of children up to 6 years of age. Data were analyzed for
      1864 participants. Binary logistic regression models showed that, after
      controlling for socio-demographics and children's age, parents who had better
      vaccine literacy (<0.05) were more likely to trust and choose domestically
      produced vaccines, which account for about 95% of the total vaccinations in
      China. This study provides evidence on a still largely understudied relationship
      between vaccine literacy and vaccination-related outcomes. Findings might suggest
      that higher literacy levels could reduce some of the negative effects of being
      exposed to misleading information on vaccination, eventually leading to less
      vaccination hesitancy.

PMID- 29589808
TI  - On the Role of Cognitive Abilities in Second Language Vowel Learning.
AB  - This study investigated the role of different cognitive abilities-inhibitory
      control, attention control, phonological short-term memory (PSTM), and acoustic
      short-term memory (AM)-in second language (L2) vowel learning. The participants
      were 40 Azerbaijani learners of Standard Southern British English. Their
      perception of L2 vowels was tested through a perceptual discrimination task
      before and after five sessions of high-variability phonetic training. Inhibitory
      control was significantly correlated with gains from training in the
      discrimination of L2 vowel pairs. However, there were no significant correlations
      between attention control, AM, PSTM, and gains from training. These findings
      suggest the potential role of inhibitory control in L2 phonological learning. We
      suggest that inhibitory control facilitates the processing of L2 sounds by
      allowing learners to ignore the interfering information from L1 during training,
      leading to better L2 segmental learning.

PMID- 29589809
TI  - Breast cancer literacy and health beliefs related to breast cancer screening
      among American Indian women.
AB  - The purpose of this article is to examine the health beliefs and literacy about
      breast cancer and their relationship with breast cancer screening among American
      Indian (AI) women. Using the Health Belief Model (HBM) and hierarchical logistic
      regression with data from a sample of 286 AI female adults residing in the
      Northern Plains, we found that greater awareness of breast cancer screening was
      linked to breast cancer screening practices. However, perceived barriers, one of
      the HBM constructs, prevented such screening practices. This study suggested that
      culturally relevant HBM factors should be targeted when developing culturally
      sensitive breast cancer prevention efforts.

PMID- 29589810
TI  - Visuomotor learning is dependent on direction-specific error saliency.
AB  - People perceive better in cardinal directions compared with oblique ones. This
      directional effect, called oblique effect, has been documented in perception
      studies for a long time. However, typical motor studies do not differentiate
      learning in different directions. In this study we identify a significant
      directional effect in motor learning using visuomotor rotation paradigms. We find
      that adaptation to visual perturbations yields more savings when both initial
      learning and relearning are performed in cardinal directions than in oblique
      directions. We hypothesize that this directional effect arises from relatively
      higher error saliency in cardinal directions. Consistent with this hypothesis, we
      successfully increased savings in the oblique directions, which showed no saving
      effect before, by enhancing the error saliency with augmented visual feedback
      during learning. Our findings suggest that movement direction plays an important
      role in motor learning, especially when learning signals are direction specific.
      Our results also provide new insights about the role of motor errors in the
      formation and retrieval of motor memory and practical implications for promoting
      learning in motor rehabilitation and athletic training. NEW & NOTEWORTHY People
      perceive better when the stimulus is in cardinal directions than in oblique
      directions. Whether a similar directional effect exists in motor learning is
      unknown. Using a motor learning paradigm, we show that people relearn to
      compensate for a previously encountered perturbation faster when they move in
      cardinal directions than when they move in oblique directions. Further
      experimentation supports that this motor directional effect likely results from
      better sensory saliency of motor errors in cardinal directions.

PMID- 29589811
TI  - Differential effects of adaptation on odor discrimination.
AB  - Adaptation of neural responses is ubiquitous in sensory systems and can
      potentially facilitate many important computational functions. Here we examined
      this issue with a well-constrained computational model of the early olfactory
      circuits. In the insect olfactory system, the responses of olfactory receptor
      neurons (ORNs) on the antennae adapt over time. We found that strong adaptation
      of sensory input is important for rapidly detecting a fresher stimulus
      encountered in the presence of other background cues and for faithfully
      representing its identity. However, when the overlapping odorants were chemically
      similar, we found that adaptation could alter the representation of these
      odorants to emphasize only distinguishing features. This work demonstrates novel
      roles for peripheral neurons during olfactory processing in complex environments.
      NEW & NOTEWORTHY Olfactory systems face the problem of distinguishing salient
      information from a complex olfactory environment. The neural representations of
      specific odor sources should be consistent regardless of the background. How are
      olfactory representations robust to varying environmental interference? We show
      that in locusts the extraction of salient information begins in the periphery.
      Olfactory receptor neurons adapt in response to odorants. Adaptation can provide
      a computational mechanism allowing novel odorant components to be highlighted
      during complex stimuli.

PMID- 29589813
TI  - Proximal and distal modulation of neural activity by spatially confined
      optogenetic activation with an integrated high-density optoelectrode.
AB  - Optogenetic manipulations are widely used for investigating the contribution of
      genetically identified cell types to behavior. Simultaneous electrophysiological
      recordings are less common, although they are critical for characterizing the
      specific impact of optogenetic manipulations on neural circuits in vivo. This is
      at least in part because combining photostimulation with large-scale
      electrophysiological recordings remains technically challenging, which also poses
      a limitation for performing extracellular identification experiments. Currently
      available interfaces that guide light of the appropriate wavelength into the
      brain combined with an electrophysiological modality suffer from various
      drawbacks such as a bulky size, low spatial resolution, heat dissipation, or
      photovoltaic artifacts. To address these challenges, we have designed and
      fabricated an integrated ultrathin neural interface with 12 optical outputs and
      24 electrodes. We used the device to measure the effect of localized stimulation
      in the anterior olfactory cortex, a paleocortical structure involved in olfactory
      processing. Our experiments in adult mice demonstrate that because of its small
      dimensions, our novel tool causes far less tissue damage than commercially
      available devices. Moreover, optical stimulation and recording can be performed
      simultaneously, with no measurable electrical artifact during optical
      stimulation. Importantly, optical stimulation can be confined to small volumes
      with approximately single-cortical layer thickness. Finally, we find that even
      highly localized optical stimulation causes inhibition at more distant sites. NEW
      & NOTEWORTHY In this study, we establish a novel tool for simultaneous
      extracellular recording and optogenetic photostimulation. Because the device is
      built using established microchip technology, it can be fabricated with high
      reproducibility and reliability. We further show that even very localized
      stimulation affects neural firing far beyond the stimulation site. This
      demonstrates the difficulty in predicting circuit-level effects of optogenetic
      manipulations and highlights the importance of closely monitoring neural activity
      in optogenetic experiments.

PMID- 29589812
TI  - Muscle coactivation: definitions, mechanisms, and functions.
AB  - The phenomenon of agonist-antagonist muscle coactivation is discussed with
      respect to its consequences for movement mechanics (such as increasing joint
      apparent stiffness, facilitating faster movements, and effects on action
      stability), implication for movement optimization, and involvement of different
      neurophysiological structures. Effects of coactivation on movement stability are
      ambiguous and depend on the effector representing a kinematic chain with a fixed
      origin or free origin. Furthermore, coactivation is discussed within the
      framework of the equilibrium-point hypothesis and the idea of hierarchical
      control with spatial referent coordinates. Relations of muscle coactivation to
      changes in one of the basic commands, the c-command, are discussed and
      illustrated. A hypothesis is suggested that agonist-antagonist coactivation
      reflects a deliberate neural control strategy to preserve effector-level control
      and avoid making it degenerate and facing the necessity to control at the level
      of signals to individual muscles. This strategy, in particular, allows
      stabilizing motor actions by covaried adjustments in spaces of control variables.
      This hypothesis is able to account for higher levels of coactivation in young
      healthy persons performing challenging tasks and across various populations with
      movement impairments.

PMID- 29589814
TI  - Gap encoding by parvalbumin-expressing interneurons in auditory cortex.
AB  - Synaptic inhibition shapes the temporal processing of sounds in auditory cortex,
      but the contribution of specific inhibitory cell types to temporal processing
      remains unclear. We recorded from parvalbumin-expressing (PV+) interneurons in
      auditory cortex to determine how they encode gaps in noise, a model of temporal
      processing more generally. We found that PV+ cells had stronger and more
      prevalent on-responses, off-responses, and postresponse suppression compared with
      presumed pyramidal cells. We summarize this pattern of differences as "deeper
      modulation" of gap responses in PV+ cells. Response latencies were also markedly
      faster for PV+ cells. We found a similar pattern of deeper modulation and faster
      latencies for responses to white noise bursts, suggesting that these are general
      properties of on- and off-responses in PV+ cells rather than specific features of
      gap encoding. These findings are consistent with a role for PV+ cells in
      providing dynamic gain control by pooling local activity. NEW & NOTEWORTHY We
      found that parvalbumin-expressing (PV+) interneurons in auditory cortex showed
      more deeply modulated responses to both gaps in noise and bursts of noise,
      suggesting that they are optimized for the rapid detection of stimulus
      transients.

PMID- 29589815
TI  - Primary sensorimotor cortex exhibits complex dependencies of spike-field
      coherence on neuronal firing rates, field power, and behavior.
AB  - Spike-field coherence (SFC) is widely used to assess cortico-cortical
      interactions during sensorimotor behavioral tasks by measuring the consistency of
      the relative phases between the spike train of a neuron and the concurrent local
      field potentials (LFPs). Interpretations of SFC as a measure of functional
      connectivity are complicated by theoretical work suggesting that estimates of SFC
      depend on overall neuronal activity. We evaluated the dependence of SFC on
      neuronal firing rates, LFP power, and behavior in the primary motor (MIo) and
      primary somatosensory (SIo) areas of the orofacial sensorimotor cortex of monkeys
      ( Macaca mulatta) during performance of a tongue-protrusion task. Although we
      occasionally observed monotonically increasing linear relationships between
      coherence and firing rate, we most often found highly complex, nonmonotonic
      relationships in both SIo and MIo and sometimes even found that coherence
      decreased with increasing firing rate. The lack of linear relationships was also
      true for both LFP power and tongue-protrusive force. Moreover, the ratio between
      maximal firing rate and the firing rate at peak coherence deviated significantly
      from unity, indicating that MIo and SIo neurons achieved maximal SFC at a
      submaximal level of spiking. Overall, these results point to complex
      relationships of SFC to firing rates, LFP power, and behavior during sensorimotor
      cortico-cortical interactions: coherence is a measure of functional connectivity
      whose magnitude is not a mere monotonic reflection of changes in firing rate, LFP
      power, or the relevantly controlled behavioral parameter. NEW & NOTEWORTHY The
      concern that estimates of spike-field coherence depend on the firing rates of
      single neurons has influenced analytical methods employed by experimental studies
      investigating the functional interactions between cortical areas. Our study shows
      that the overwhelming majority of the estimated spike-field coherence exhibited
      complex relations with firing rates of neurons in the orofacial sensorimotor
      cortex. The lack of monotonic relations was also evident after testing the
      influence of local field potential power and force on spike-field coherence.

PMID- 29589816
TI  - Modulation of complex spike activity differs between zebrin-positive and 
      negative Purkinje cells in the pigeon cerebellum.
AB  - The cerebellum is organized into parasagittal zones defined by its climbing and
      mossy fiber inputs, efferent projections, and Purkinje cell (PC) response
      properties. Additionally, parasagittal stripes can be visualized with molecular
      markers, such as heterogeneous expression of the isoenzyme zebrin II (ZII), where
      sagittal stripes of high ZII expression (ZII+) are interdigitated with stripes of
      low ZII expression (ZII-). In the pigeon vestibulocerebellum, a ZII+/- stripe
      pair represents a functional unit, insofar as both ZII+ and ZII- PCs within a
      stripe pair respond best to the same pattern of optic flow. In the present study,
      we attempted to determine whether there were any differences in the responses
      between ZII+ and ZII- PCs within a functional unit in response to optic flow
      stimuli. In pigeons of either sex, we recorded complex spike activity (CSA) from
      PCs in response to optic flow, marked recording sites with a fluorescent tracer,
      and determined the ZII identity of recorded PCs by immunohistochemistry. We found
      that CSA of ZII+ PCs showed a greater depth of modulation in response to the
      preferred optic flow pattern compared with ZII- PCs. We suggest that these
      differences in the depth of modulation to optic flow stimuli are due to
      differences in the connectivity of ZII+ and ZII- PCs within a functional unit.
      Specifically, ZII+ PCs project to areas of the vestibular nuclei that provide
      inhibitory feedback to the inferior olive, whereas ZII- PCs do not. NEW &
      NOTEWORTHY Although the cerebellum appears to be a uniform structure, Purkinje
      cells (PCs) are heterogeneous and can be categorized on the basis of the
      expression of molecular markers. These phenotypes are conserved across species,
      but the significance is undetermined. PCs in the vestibulocerebellum encode optic
      flow resulting from self-motion, and those that express the molecular marker
      zebrin II (ZII+) exhibit more sensitivity to optic flow than those that do not
      express zebrin II (ZII-).

PMID- 29589819
TI  - Eating disorders: The journal of treatment and prevention new editors' vision
      statement.

PMID- 29589818
TI  - A Standardized Education Checklist for Parents of Children Newly Diagnosed With
      Cancer: A Report From the Children's Oncology Group.
AB  - Parents of children newly diagnosed with cancer must acquire new knowledge and
      skills in order to safely care for their child at home. Institutional variation
      exists in the methods and content used by nurses in providing the initial
      education. The goal of this project was to develop a checklist, standardized
      across institutions, to guide nursing education provided to parents of children
      newly diagnosed with cancer. A team of 21 members (19 nurses and 2 parent
      advocates) used current hospital educational checklists, expert consensus
      recommendations, and a series of iterative activities and discussions to develop
      one standardized checklist. The final checklist specifies primary topics that are
      essential to teach prior to the initial hospital discharge, secondary topics that
      should be discussed within the first month after the cancer diagnosis, and
      tertiary topics that should be discussed prior to completion of therapy. This
      checklist is designed to guide education and will set the stage for future
      studies to identify effective teaching strategies that optimize the educational
      process for parents of children newly diagnosed with cancer.

PMID- 29589817
TI  - Neurophysiological changes in the visuomotor network after practicing a motor
      task.
AB  - Although it is well appreciated that practicing a motor task updates the
      associated internal model, it is still unknown how the cortical oscillations
      linked with the motor action change with practice. The present study investigates
      the short-term changes (e.g., fast motor learning) in the alpha- and beta-event
      related desynchronizations (ERD) associated with the production of a motor
      action. To this end, we used magnetoencephalography to identify changes in the
      alpha- and beta-ERD in healthy adults after participants practiced a novel
      isometric ankle plantarflexion target-matching task. After practicing, the
      participants matched the targets faster and had improved accuracy, faster force
      production, and a reduced amount of variability in the force output when trying
      to match the target. Parallel with the behavioral results, the strength of the
      beta-ERD across the motor-planning and execution stages was reduced after
      practice in the sensorimotor and occipital cortexes. No pre/postpractice changes
      were found in the alpha-ERD during motor planning or execution. Together, these
      outcomes suggest that fast motor learning is associated with a decrease in beta
      ERD power. The decreased strength likely reflects a more refined motor plan, a
      reduction in neural resources needed to perform the task, and/or an enhancement
      of the processes that are involved in the visuomotor transformations that occur
      before the onset of the motor action. These results may augment the development
      of neurologically based practice strategies and/or lead to new practice
      strategies that increase motor learning. NEW & NOTEWORTHY We aimed to determine
      the effects of practice on the movement-related cortical oscillatory activity.
      Following practice, we found that the performance of the ankle plantarflexion
      target-matching task improved and the power of the beta-oscillations decreased in
      the sensorimotor and occipital cortexes. These novel findings capture the beta
      oscillatory activity changes in the sensorimotor and occipital cortexes that are
      coupled with behavioral changes to demonstrate the effects of motor learning.

PMID- 29589820
TI  - Text Messaging to Improve Disease Management in Patients With Painful Diabetic
      Peripheral Neuropathy.
AB  - Purpose The purpose of the study was to determine the impact of educational text
      messages on diabetes self-management activities and outcomes in patients with
      painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN
      identified from a large integrated health system who agreed to participate were
      randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self
      management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating
      Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes
      health beliefs, and glycated hemoglobin (A1C). Changes from baseline were
      evaluated at 6 months and compared between groups. Results Demographic
      characteristics were balanced between groups (N = 62; 53% female, mean age = 63
      years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain
      decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no
      difference between groups. UC+TxtM but not UC was associated with significant
      improvements from baseline on all SDSCA subscales. On diabetes health beliefs,
      UC+TxtM patients reported significantly increased benefits and reduced barriers
      and susceptibility relative to UC at 6 months. A1C declined in both groups, but
      neither change was significant relative to baseline. Conclusions Patients with
      pDPN who receive twice-daily text messages regarding diabetes management reported
      reduced pain relative to baseline, although this change was not significant
      compared with usual care. In addition, text messaging was associated with
      increased self-management activities and improved diabetes health beliefs and
      total self-care. These results warrant further investigation.

PMID- 29589821
TI  - The 2017 Diabetes Educator and the Diabetes Self-Management Education National
      Practice Survey.
AB  - Purpose The American Association of Diabetes Educators conducts the National
      Practice Survey (NPS) biennially to document current practice in diabetes
      education in the United States. The purpose of the study is to obtain insight
      about factors influencing the work of the diabetes educator. Method The 2017 NPS
      was comprised of 100 questions covering diabetes educator demographics, profile
      populations of people with diabetes, practice information, program accreditation,
      program curriculum, staffing, education delivery methods, data collection, and
      reporting. The basic survey consisted of 22 questions using branch logic, from
      which respondents were then directed to questions tailored to their particular
      practice setting, enabling them to answer only a relevant subset of the remaining
      questions. The web-based survey was sent to approximately 32 000 individuals who
      were either members of the American Association of Diabetes Educators (AADE) or
      Certified Diabetes Educators (CDE) with the National Certification Board for
      Diabetes Educators (NCBDE) but not AADE members. Weekly reminder e-mails were
      sent to recipients who had not yet responded. The outreach efforts resulted in
      the survey being completed by 4696 individuals, a 17% response rate yielding 95%
      confidence that these responses are within +/-5% accuracy. Results Diabetes Self
      Management Education and Support (DSMES) continues to be a field dominated by
      women (95%). Diabetes educators represent a diverse health care profession, with
      educators indicating most commonly that their primary discipline is nursing
      (48%), nutrition (38%), and pharmacy (7%). When asked about credentials, 82.6%
      indicated that they held a CDE, 3.8% held the Board Certified-Advanced Diabetes
      Management (BC-ADM) credential, and 16.5% held neither the CDE nor the BC-ADM.
      Nearly 75% characterized their role as a diabetes educator as providing direct
      patient care. DSMES continued to be provided in a varied array of settings to
      educationally, socioeconomically, and racially diverse patient populations. DSMES
      was delivered using a number of different educational strategies. Diabetes
      educators have direct influence in care and services that people with diabetes
      receive. Conclusions The results of the 2017 NPS demonstrate that diabetes
      educators are meeting the needs of varied populations in various practice
      settings. They are working with individuals with type 1 and type 2 diabetes,
      those at risk for diabetes, and women with gestational diabetes and are involved
      in recommending, implementing, and providing key referrals and recommendations
      for diabetes care, including insulin initiation, titration, medication
      adjustments, recommendations on devices, and technology. Identified areas for
      improvement include needs for increased racial and ethnic diversity in the
      workforce, recruiting young professionals, drawing practice approaches from
      related disciplines (eg, mental health and disability rehabilitation), and
      encouraging tracking of more areas of outcomes data. Diabetes educators are
      playing an increasingly central role within multidisciplinary care teams with
      people at risk for diabetes, those who have diabetes, and those with other
      chronic conditions.

PMID- 29589822
TI  - Editorial: Bone Drug Targets.

PMID- 29589823
TI  - Editorial: Identifying Drug-target Interactions Based on Heterogeneous Biological
      Data - PART 1.

PMID- 29589825
TI  - Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus
      Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell
      Transplant Recipients.
AB  - We examined vancomycin-resistant enterococci (VRE)-directed antimicrobial use and
      VRE bacteremia in a cohort of allogeneic hematopoietic cell transplantation
      patients from a center where VRE screening is standard prior to transplant. In
      this cohort, VRE bacteremia (VREB) was infrequent. In patients without VREB,
      colonized patients received VRE therapy more often than noncolonized
      patients.Infect Control Hosp Epidemiol 2018;39:730-733.

PMID- 29589826
TI  - ICTV Virus Taxonomy Profile: Hypoviridae.
AB  - The Hypoviridae, comprising one genus, Hypovirus, is a family of capsidless
      viruses with positive-sense, ssRNA genomes of 9.1-12.7 kb that possess either a
      single large ORF or two ORFs. The ORFs appear to be translated from genomic RNA
      by non-canonical mechanisms, i.e. internal ribosome entry site-mediated and
      stop/restart translation. Hypoviruses have been detected in ascomycetous or
      basidiomycetous filamentous fungi, and are considered to be replicated in host
      Golgi-derived, lipid vesicles that contain their dsRNA as a replicative form.
      Some hypoviruses induce hypovirulence to host fungi, while others do not. This is
      a summary of the current ICTV report on the taxonomy of the Hypoviridae, which is
      available at www.ictv.global/report/hypoviridae.

PMID- 29589827
TI  - The changing use of the ovipositor in host shifts by ichneumonid ectoparasitoids
      of spiders (Hymenoptera, Ichneumonidae, Pimplinae).
AB  - Accurate egg placement into or onto a living host is an essential ability for
      many parasitoids, and changes in associated phenotypes, such as ovipositor
      morphology and behaviour, correlate with significant host shifts. Here, we report
      that in the ichneumonid group of koinobiont spider-ectoparasitoids
      ("polysphinctines"), several putatively ancestral taxa (clade I here), parasitic
      on ground-dwelling RTA-spiders (a group characterised by retrolateral tibial
      apophysis on male palpal tibiae), lay their eggs in a specific way. They tightly
      bend their metasoma above the spider's cephalothorax, touching the carapace with
      the dorsal side of the ovipositor apically ("dorsal-press"). The egg slips out
      from the middle part of the ventral side of the ovipositor and moves towards its
      apex with the parted lower valves acting as rails. Deposition occurs as the
      parasitoid draws the ovipositor backwards from under the egg. Oviposition upon
      the tough carapace of the cephalothorax, presumably less palatable than the
      abdomen, is conserved in these taxa, and presumed adaptive through avoiding
      physical damage to the developing parasitoid. This specific way of oviposition is
      reversed in the putatively derived clade of polysphinctines (clade II here)
      parasitic on Araneoidea spiders with aerial webs, which is already known. They
      bend their metasoma along the spider's abdomen, grasping the abdomen with their
      fore/mid legs, pressing the ventral tip of the metasoma and the lower valves of
      the ovipositor against the abdomen ("ventral-press"). The egg is expelled through
      an expansion of the lower valves, which is developed only in this clade and
      evident in most species, onto the softer and presumably more nutritious abdomen.

PMID- 29589828
TI  - Structural and functional properties of a probabilistic model of neuronal
      connectivity in a simple locomotor network.
AB  - Although, in most animals, brain connectivity varies between individuals,
      behaviour is often similar across a species. What fundamental structural
      properties are shared across individual networks that define this behaviour? We
      describe a probabilistic model of connectivity in the hatchling Xenopus tadpole
      spinal cord which, when combined with a spiking model, reliably produces rhythmic
      activity corresponding to swimming. The probabilistic model allows calculation of
      structural characteristics that reflect common network properties, independent of
      individual network realisations. We use the structural characteristics to study
      examples of neuronal dynamics, in the complete network and various sub-networks,
      and this allows us to explain the basis for key experimental findings, and make
      predictions for experiments. We also study how structural and functional features
      differ between detailed anatomical connectomes and those generated by our new,
      simpler, model (meta-model).

PMID- 29589829
TI  - Comprehensive machine learning analysis of Hydra behavior reveals a stable basal
      behavioral repertoire.
AB  - Animal behavior has been studied for centuries, but few efficient methods are
      available to automatically identify and classify it. Quantitative behavioral
      studies have been hindered by the subjective and imprecise nature of human
      observation, and the slow speed of annotating behavioral data. Here, we developed
      an automatic behavior analysis pipeline for the cnidarian Hydra vulgaris using
      machine learning. We imaged freely behaving Hydra, extracted motion and shape
      features from the videos, and constructed a dictionary of visual features to
      classify pre-defined behaviors. We also identified unannotated behaviors with
      unsupervised methods. Using this analysis pipeline, we quantified 6 basic
      behaviors and found surprisingly similar behavior statistics across animals
      within the same species, regardless of experimental conditions. Our analysis
      indicates that the fundamental behavioral repertoire of Hydra is stable. This
      robustness could reflect a homeostatic neural control of "housekeeping" behaviors
      which could have been already present in the earliest nervous systems.

PMID- 29589830
TI  - Transmission genetics of drug-resistant hepatitis C virus.
AB  - Antiviral development is plagued by drug resistance and genetic barriers to
      resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy
      has proved life-saving. The targets of direct-acting antivirals for HCV infection
      are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential
      visualization of drug-resistant and -susceptible RNA genomes within cells
      revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are
      cis-dominant, ensuring their direct selection from complex environments. Confocal
      microscopy revealed that RNA replication complexes are genome-specific,
      rationalizing the non-interaction of wild-type and variant products. No HCV
      antivirals yet display the dominance of drug susceptibility shown for capsid
      proteins of other viruses. However, effective inhibitors of HCV polymerase exact
      such high fitness costs for drug resistance that stable genome selection is not
      observed. Barriers to drug resistance vary with target biochemistry and detailed
      analysis of these barriers should lead to the use of fewer drugs.

PMID- 29589831
TI  - Cellular tolerance at the u-opioid receptor is phosphorylation dependent.
AB  - Phosphorylation of the MU-opioid receptor (MOR) is known as a key step in
      desensitization and internalization but the role in the development of long-term
      tolerance at the cellular level is not known. Viral expression of wild type
      (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total
      Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus
      coeruleus neurons in a MOR knockout rat. Both receptors activated potassium
      conductance similar to endogenous receptors in wild type animals. The exWT
      receptors, like endogenous receptors, acutely desensitized, internalized and,
      after chronic morphine treatment, displayed signs of tolerance. However, TPD
      receptors did not desensitize or internalize with agonist treatment. In addition
      the TPD receptors did not develop cellular tolerance following chronic morphine
      treatment. Thus C-terminal phosphorylation is necessary for the expression of
      acute desensitization, trafficking and one sign of long-term tolerance to
      morphine at the cellular level.

PMID- 29589832
TI  - Acute Traumatic Coagulopathy: The Value of Histone in Pediatric Trauma Patients.
AB  - OBJECTIVE: Acute traumatic coagulopathy occurs after trauma with impairment of
      hemostasis and activation of fibrinolysis. Some endogenous substances may play
      roles in this failure of the coagulation system. Extracellular histone is one
      such molecule that has recently attracted attention. This study investigated the
      association between plasma histone-complexed DNA (hcDNA) fragments and
      coagulation abnormalities in pediatric trauma patients. MATERIALS AND METHODS:
      This prospective case-control study was conducted in pediatric patients with
      trauma. Fifty trauma patients and 30 healthy controls were enrolled. Demographic
      data, anatomic injury characteristics, coagulation parameters, computerized
      tomography findings, trauma, and International Society on Thrombosis and
      Haemostasis disseminated intravascular coagulation (ISTH DIC) scores were
      recorded. Blood samples for hcDNA were collected and assessed by enzyme-linked
      immunosorbent assay. RESULTS: Thirty-two patients had multiple trauma, while 18
      patients had isolated brain injury. hcDNA levels were significantly higher in
      trauma patients than healthy controls (0.474 AU and 0.145 AU, respectively).
      There was an association between plasma hcDNA levels and trauma severity.
      Thirteen patients had acute coagulopathy of trauma shock (ACoTS). ACoTS patients
      had higher plasma histone levels than those without ACoTS (0.703 AU and 0.398 AU,
      respectively). Plasma hcDNA levels were positively correlated with the ISTH DIC
      score and length of stay in the intensive care unit and were negatively
      correlated with fibrinogen level. CONCLUSION: This study indicated that hcDNA
      levels were increased in pediatric trauma patients and associated with the early
      phase of coagulopathy. Further studies are needed to clarify the role of hcDNA
      levels in mortality and disseminated intravascular coagulation.

PMID- 29589833
TI  - Anemia Associated with Worse Outcome in Diffuse Large B-Cell Lymphoma Patients: A
      Single-Center Retrospective Study
AB  - Objective: Useful prognostic biomarkers for diffuse large B-cell lymphoma (DLBCL)
      patients have been reported. To determine the prognostic value of hemoglobin (Hb)
      level in DLBCL patients, we performed a retrospective study. Materials and
      Methods: We evaluated disease outcome, progression-free survival (PFS), overall
      survival as the endpoint, and clinical and laboratory factors affecting the
      outcome of 185 DLBCL patients who had received rituximab, cyclophosphamide,
      doxorubicin, vincristine, and prednisolone therapy during 2004-2014. Results: The
      study group included 121 men and 64 women with a median age of 66 years minimum
      maximum: 21-83 years. In univariate analysis, factors independently associated
      with worse PFS were Eastern Cooperative Oncology Group performance status >=2,
      Ann Arbor stage III or IV, anemia with Hb levels of <10 g/dL, and serum albumin
      of <3.5 g/dL. In multivariate analysis, anemia with Hb levels of <10 g/dL and Ann
      Arbor stage III or IV were found to be international index-independent prognostic
      factors (hazard ratio: 2.4; p=0.04). Conclusion: Anemia is an independent
      prognostic marker of poor outcome in DLBCL patients. Hb can be an easily
      available prognostic marker for risk stratification in these patients.

PMID- 29589834
TI  - Hierarchical Involvement of Myeloid-Derived Suppressor Cells and Monocytes
      Expressing Latency-Associated Peptide in Plasma Cell Dyscrasias.
AB  - OBJECTIVE: Plasma cell dyscrasias (PCDs) are disorders of plasma cells having in
      common the production of a monoclonal M-protein. They include a spectrum of
      conditions that may represent a natural progression of the same disease from
      monoclonal gammopathy of unknown significance to asymptomatic and symptomatic
      multiple myeloma, plasma cell leukemia, and Waldenstrom's macroglobulinemia. In
      PCDs, the immune system is actively suppressed through the secretion of
      suppressive factors and the recruitment of immune suppressive subpopulations. In
      this study, we examined the expression of two subpopulations of cells with
      immunosuppressive activity, monocytic myeloid-derived suppressor cells (MDSCs)
      and monocytes expressing latency-associated peptide (LAP), in patients with
      different PCDs and in healthy volunteers. MATERIALS AND METHODS: A total of 27
      consecutive patients with PCDs were included in this study. Nineteen healthy
      volunteers served as controls. RESULTS: We observed a hierarchical correlation
      between disease activity and the presence of monocytes with immunosuppressive
      activity. CONCLUSION: These results suggest that MDSCs and monocytes expressing
      LAP have diverging roles in PCDs and may perhaps serve as biomarkers of tumor
      activity and bulk.

PMID- 29589835
TI  - SNC80 and naltrindole modulate voltage-dependent sodium, potassium and calcium
      channels via a putatively delta opioid receptor-independent mechanism.
AB  - SNC80 was designed as a highly selective nonpeptide delta opioid receptor (DOR)
      agonist. Antidepressant-like and antinociceptive effects of this compound were
      demonstrated in animal models. Naltrindole was synthetized as a highly selective
      DOR antagonist. Its antitussive and antinociceptive effects were reported.
      Observed effects of SNC80 and naltrindole may be accompanied by changes in
      neuronal excitability including modulation of voltage-dependent ion channels. We
      investigated possible DOR-independent modulation of neuronal sodium, calcium and
      potassium currents by both agents. NG108-15 cells lacking expression of DOR
      protein were used as model of neuronal cells. Cells were differentiated into
      neuronal phenotype by exposure to dibutyryl cyclic-AMP (dbcAMP). Lack of DORs
      expression in NG108-15 cells and the presence of DOR expression in brain and
      neuronal cultures were demonstrated by Western blot analysis. Both SNC80 and
      naltrindole exerted low to moderate modulatory effects on voltage-dependent ion
      currents. SNC80 weakly inhibited sodium current, potentiated calcium current, and
      did not act on potassium channels. Naltrindole inhibited sodium current, did not
      act on calcium current and inhibited potassium current at a high concentration.
      Such effects should be taken into account when these compounds are used for
      investigation of DOR-mediated signaling pathways.

PMID- 29589836
TI  - Laser induced calcium oscillations in fluorescent calcium imaging.
AB  - Phototoxicity is the most common problem investigators may encounter when
      performing live cell imaging. It develops due to excess laser exposure of cells
      loaded with fluorophores and can lead to often overlooked but significant
      artifacts, such as massive increase of intracellular Ca2+ concentration, which
      would make data interpretation problematic. Because information about laser- and
      dye-related changes in cytoplasmic calcium concentration is very limited, we
      aimed to describe this phenomenon to help investigators using laser scanning
      confocal microscopy in a non-invasive way. Therefore, in the present study we
      evaluated fluorescent fluctuations, which evolved in Fluo-3/4/8 loaded mouse
      pancreatic acinar cells during very low intensity laser excitation. We
      demonstrate that after standard loading procedure (2 uM Fluo-3/4/8-AM, 30 min at
      room temperature), applying 488 nm laser at as low as ca. 10 uW incident laser
      power (0.18 uW/um2) at 1 Hz caused repetitive, 2-3 fold elevations of the resting
      intracellular fluorescence. The first latency and the pattern of the fluorescence
      fluctuations were laser power dependent and were related to Ca2+-release from
      intracellular stores, as they were abolished by BAPTA-AM treatment in Ca2+-free
      medium, but were not diminished by the reactive oxygen species (ROS) scavenger
      DMPO. Worryingly enough, the qualitative and quantitative features of the Ca2+
      waves were practically indistinguishable from the responses evoked by
      secretagogue stimulation. Since using similar imaging conditions, a number of
      other cell types were reported to display spontaneous Ca2+ oscillations, we
      propose strategies to distinguish the real signals from artifacts.

PMID- 29589837
TI  - Blood pressure management and progression of chronic kidney disease in a canine
      remnant kidney model.
AB  - The canine remnant kidney model is fundamental to understanding the relationship
      between hypertension and chronic kidney disease (CKD). This study aimed to create
      a 1/16 remnant kidney model and to determine whether blood pressure (BP) control
      affects the progression of CKD. A group of dogs received BP treatment (group A)
      and another received BP treatment except for the first 2 weeks (group B). The
      remnant kidney model was induced using a two-step subtotal nephrectomy method;
      dogs received antihypertensive therapy. Systolic BP, blood urea nitrogen, serum
      creatinine, urinary protein, and creatinine levels were measured weekly. Kidney
      tissues were obtained at the conclusion of the study. Systolic BP was controlled
      to <160 mmHg in both groups for 18 weeks, except for the first 2 weeks in group
      B. Proteinuria was elevated after renal ligation in both groups, but gradually
      increased in group B and decreased in group A (p = 0.009). Blood urea nitrogen (p
      = 0.014) and creatinine (p = 0.020) levels were higher in group B than in group
      A. More histological damage was observed in group B than in group A. Induction of
      1/16 nephrectomy successfully established CKD. Control of BP may be important to
      prevent or control the progression of CKD in dogs.

PMID- 29589838
TI  - Electronic structure and charge transport in nonstoichiometric tantalum oxide.
AB  - The atomic and electronic structure of nonstoichiometric oxygen-deficient
      tantalum oxide TaO x<2.5 grown by ion beam sputtering deposition was studied. The
      TaO x film content was analyzed by x-ray photoelectron spectroscopy and by
      quantum-chemistry simulation. TaO x is composed of Ta2O5, metallic tantalum
      clusters and tantalum suboxides. A method for evaluating the stoichiometry
      parameter of TaO x from the comparison of experimental and theoretical
      photoelectron valence band spectra is proposed. The charge transport properties
      of TaO x were experimentally studied and the transport mechanism was
      quantitatively analyzed with four theoretical dielectric conductivity models. It
      was found that the charge transport in almost stoichiometric and
      nonstoichiometric tantalum oxide can be consistently described by the phonon
      assisted tunneling between traps.

PMID- 29589841
TI  - A facile method for the synthesis of fused perhydropyrano[2,3-b]pyrans promoted
      by Yb(OTf)3.
AB  - A stereospecific three-component domino reaction between glycals, alkylidene
      malonate and aldehydes catalyzed by Yb(OTf)3 is described. Multi-substituted cis
      fused perhydropyrano[2,3-b]pyran derivatives were obtained with high
      diastereoselectivity.

PMID- 29589839
TI  - PPARgamma deacetylation dissociates thiazolidinedione's metabolic benefits from
      its adverse effects.
AB  - Thiazolidinediones (TZDs) are PPARgamma agonists with potent insulin-sensitizing
      effects. However, their use has been curtailed by substantial adverse effects on
      weight, bone, heart, and hemodynamic balance. TZDs induce the deacetylation of
      PPARgamma on K268 and K293 to cause the browning of white adipocytes. Here, we
      show that targeted PPARgamma mutations resulting in constitutive deacetylation
      (K268R/K293R, 2KR) increased energy expenditure and protected from visceral
      adiposity and diet-induced obesity by augmenting brown remodeling of white
      adipose tissues. Strikingly, when 2KR mice were treated with rosiglitazone, they
      maintained the insulin-sensitizing, glucose-lowering response to TZDs, while
      displaying little, if any, adverse effects on fat deposition, bone density, fluid
      retention, and cardiac hypertrophy. Thus, deacetylation appears to fulfill the
      goal of dissociating the metabolic benefits of PPARgamma activation from its
      adverse effects. Strategies to leverage PPARgamma deacetylation may lead to the
      design of safer, more effective agonists of this nuclear receptor in the
      treatment of metabolic diseases.

PMID- 29589840
TI  - The Atypical Chemokine Receptor ACKR2 is Protective Against Sepsis.
AB  - Sepsis is a systemic inflammatory response as a result of uncontrolled
      infections. Neutrophils are the first cells to reach the primary sites of
      infection, and chemokines play a key role in recruiting neutrophils. However, in
      sepsis chemokines could also contribute to neutrophil infiltration to vital
      organs leading to multiple organ failure. ACKR2 is an atypical chemokine
      receptor, which can remove and degrade inflammatory CC chemokines. The role of
      ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we
      demonstrate here that ACKR2 deficient () mice exhibited a significant reduction
      in the survival rate compared with similarly treated wild-type (WT) mice.
      However, neutrophil migration to the peritoneal cavity and bacterial load were
      similar between WT and ACKR2 mice during CLP. In contrast, ACKR2 mice showed
      increased neutrophil infiltration and elevated CC chemokine levels in the lung,
      kidney, and heart compared with the WT mice. In addition, ACKR2 mice also showed
      more severe lesions in the lung and kidney than those in the WT mice. Consistent
      with these results, WT mice under nonsevere sepsis (90% survival) had higher
      expression of ACKR2 in these organs than mice under severe sepsis (no survival).
      Finally, the lungs from septic patients showed increased number of ACKR2 cells
      compared with those of nonseptic patients. Our data indicate that ACKR2 may have
      a protective role during sepsis, and the absence of ACKR2 leads to exacerbated
      chemokine accumulation, neutrophil infiltration, and damage to vital organs.

PMID- 29589842
TI  - Lyophobicity may not be the main driving force for long chain surfactants from
      the bulk phase to the interface.
AB  - According to the Traube rule, a surfactant with a longer alkane chain is more
      hydrophobic so its tendency to be driven from a polar solvent to a less polar
      interface is higher. In this work, we revisited this topic by studying the
      adsorption of quaternary ammonium salts and carboxylic acids with various alkane
      chain lengths at the hexadecane-water interface. The adsorption free energies of
      the surfactants at this oil-water interface from the polar (aqueous solution) or
      nonpolar phase (hexadecane) were estimated from second harmonic generation
      measurements. The variation of the free energies per methylene group in the bulk
      phase, at the oil-water interface and at the air-water interface revealed that
      there are different interactions between the alkane chains of the surfactants in
      different environments. The chain-chain interaction at the hexadecane-water
      interface is lower than that at the air-water interface. The driving force for
      the alkane chains to adsorb at the oil-water interface from the oil phase is
      close to that from the aqueous phase. This observation reveals that the chain
      chain interaction rather than the lyophobicity of the solute with respect to the
      solvent is the main contributor to the adsorption free energy. This is the first
      experimental comparison of the free energies of the alkane chains in oil, in
      water, at the air-water interface and at the oil-water interface. These results
      provide information for studying the interactions of hydrophobic species in
      different environments. This work also provides a method for estimating the
      solvation energy of some head groups in surfactants.

PMID- 29589844
TI  - Predicting cancer cell invasion by single-cell physical phenotyping.
AB  - The physical properties of cells are promising biomarkers for cancer diagnosis
      and prognosis. Here we determine the physical phenotypes that best distinguish
      human cancer cell lines, and their relationship to cell invasion. We use the high
      throughput, single-cell microfluidic method, quantitative deformability cytometry
      (q-DC), to measure six physical phenotypes including elastic modulus, cell
      fluidity, transit time, entry time, cell size, and maximum strain at rates of 102
      cells per second. By training a k-nearest neighbor machine learning algorithm, we
      demonstrate that multiparameter analysis of physical phenotypes enhances the
      accuracy of classifying cancer cell lines compared to single parameters alone. We
      also discover a set of four physical phenotypes that predict invasion; using
      these four parameters, we generate the physical phenotype model of invasion by
      training a multiple linear regression model with experimental data from a set of
      human ovarian cancer cells that overexpress a panel of tumor suppressor
      microRNAs. We validate the model by predicting invasion based on measured
      physical phenotypes of breast and ovarian human cancer cell lines that are
      subject to genetic or pharmacologic perturbations. Taken together, our results
      highlight how physical phenotypes of single cells provide a biomarker to predict
      the invasion of cancer cells.

PMID- 29589843
TI  - PEDOT doped with algal, mammalian and synthetic dopants: polymer properties,
      protein and cell interactions, and influence of electrical stimulation on
      neuronal cell differentiation.
AB  - Poly(3,4-ethylenedioxythiophene) (PEDOT) films were electrochemically polymerised
      with several synthetic (dodecylbenzosulfonic acid (DBSA)) and biological (dextran
      sulphate (DS), chondroitin sulphate (CS), alginic acid (ALG) and ulvan (ULV))
      dopant anions, and their physical, mechanical and electrochemical properties
      characterised. PEDOT films incorporating the biological dopants ALG and ULV
      produced films of the greatest surface roughness (46 +/- 5.1 and 31 +/- 1.9 nm,
      respectively), and demonstrated significantly lower shear modulus values relative
      to all other PEDOT films (2.1 +/- 0.1 and 1.2 +/- 0.2 MPa, respectively). Quartz
      crystal microgravimetry was used to study the adsorption of the important
      extracellular matrix protein fibronectin, revealing protein adsorption to be
      greatest on PEDOT doped with DS, followed by DBSA, ULV, CS and ALG. Electrical
      stimulation experiments applying a pulsed current using a biphasic waveform (250
      Hz) were undertaken using PEDOT doped with either DBSA or ULV. Electrical
      stimulation had a significant influence on cell morphology and cell
      differentiation for PEDOT films with either dopant incorporated, with the degree
      of branching per cell increased by 10.5* on PEDOT-DBSA and 6.5* on PEDOT-ULV
      relative to unstimulated cells, and mean neurite length per cell increasing 2.6*
      and 2.2* on stimulated vs. unstimulated PEDOT-DBSA and PEDOT-ULV, respectively.
      We demonstrate the cytocompatibility of synthetic and biologically doped PEDOT
      biomaterials, including the new algal derived polysaccharide dopant ulvan, which,
      along with DBSA doped PEDOT, is shown to significantly enhance the
      differentiation of PC12 neuronal cells under electrical stimulation.

PMID- 29589845
TI  - Copper-catalyzed synthesis of thiazol-2-yl ethers from oxime acetates and
      xanthates under redox-neutral conditions.
AB  - A novel copper-catalyzed annulation of oxime acetates and xanthates for the
      synthesis of thiazol-2-yl ethers with remarkable regioselectivity has been
      developed. Various oxime acetates, whether derived from aryl ketones or alkyl
      ketones, or natural product cores are suitable for this conversion. Unique
      dihydrothiazoles were also obtained when both reaction sites were methine.
      Mechanistic studies indicated that imino copper(iii) intermediates were involved.
      In addition, this protocol proceeded under redox-neutral conditions and did not
      require additives or ligands.

PMID- 29589846
TI  - Nanocellulose templated growth of ultra-small bismuth nanoparticles for enhanced
      radiation therapy.
AB  - An unmet need in nanomedicine is to prepare biocompatible and renal clearable
      nanoparticles by controlling the diameter, composition and surface properties of
      the nanoparticles. This paper reports cellulose nanofiber templated synthesis of
      ultra-small bismuth nanoparticles, and their uses in enhanced X-ray radiation
      therapy. The interstitial spaces between adjacent fibers are the adsorption sites
      of bismuth ions and also stabilize nanoparticles generated by chemical reduction.
      The sizes of nanoparticles are tailored in the 2-10 nm range using cellulose
      nanofibers with various amounts of carboxyl groups. In vitro cytotoxicity,
      reactive oxygen species (ROS) and in vivo animal tests with tumor-bearing mice
      are studied in order to enhance X-ray radiation therapy using cellulose nanofiber
      templated bismuth nanoparticles. Bismuth nanoparticles show strong X-ray
      attenuation ability, concentration-dependent cytotoxicity and high level
      production of ROS upon X-ray exposure, which is consistent with enhanced cellular
      damage and retarded growth of tumors in animals.

PMID- 29589847
TI  - The stability limits of highly active nitrogen doped carbon ORR nano-catalysts: a
      mechanistic study of degradation reactions.
AB  - A new approach in electrode catalysis bearing immense potential for
      electrochemical technologies is the prospect of carbon-based electrodes. Pristine
      carbon nanostructures are relatively inert and modifications like nitrogen doping
      are known for their beneficial effects on the electrochemical activity of carbon
      nanomaterials in both alkaline and acidic media. However, the long-term stability
      of these materials, especially in an acidic environment, is rarely mentioned.
      Here, we evaluate the stability and long-term degradation of nitrogen doped
      graphene flakes as an oxygen reduction electrocatalyst with theoretical and
      experimental techniques. We assume that nitrogen dopants in the graphene sheet
      interact with e- and H+ at the electrode-electrolyte interface, leading to NH3
      scission and continuous catalyst deactivation. With Density Functional Theory
      calculations, NH3 scission pathways of pyridinic, graphitic and pyrrolic nitrogen
      species were analyzed and compared under different operating conditions which are
      relevant for low and intermediate temperature fuel cells. The computational
      results are correlated with electrochemical measurements in solid acid fuel cells
      in a humidified oxygen environment at 240  degrees C.

PMID- 29589848
TI  - Mechanical pressure, surface excess, and polar order of a dilute rod-like
      nanoswimmer suspension: role of swimmer-wall interactions.
AB  - The mechanical pressure, surface excess, and polar order of a dilute rod-like
      nanoswimmer suspension confined by two parallel plates are explored by
      dissipative particle dynamics. The accumulation and preferred orientation of
      swimmers near the walls are distinctly shown through the density and polar order
      distributions for various active force, Fa, values and rod lengths. As Fa is
      increased, it is interesting to observe that there exists a maximum of the polar
      order, revealing that the dominant mechanism of the swimmer behavior can be
      altered by the coupling between the active force and the rod-wall interaction. As
      a result, the influences of the active force on the swim pressure Pi(w)a
      contributed by the swimmers directly and the surface excess Gamma* can be
      classified into two scaling regimes, natural rotation (weak propulsion) and
      forced rotation (strong propulsion). Pi(w)a and Gamma* are proportional to Fa2 in
      the former regime but become proportional to Fa in the latter regime. For all rod
      wall repulsions, the swim pressure of active rods in confined systems Pi(w)a
      always differs from that in unbounded systems Pi(b)a which is simply proportional
      to Fa2 associated with the active diffusivity. That is, unlike thermal
      equilibrium systems, Pi(w)a is not a state function because of the presence of
      the wall-torque.

PMID- 29589849
TI  - Growth modes and chiral selectivity of single-walled carbon nanotubes.
AB  - Chemical vapor deposition synthesis of single-walled carbon nanotubes, using an
      Fe catalyst, and alternating methane and carbon monoxide as carbon feedstocks,
      leads to the reversible formation of junctions between tubes of different
      diameters. Combined with an atomistic modeling of the tube/catalyst interface,
      this shows that the ratio of diameters of the tube and its seeding particle,
      denoting the growth mode, depends on the carbon fraction inside the catalyst.
      With carbon monoxide, nanoparticles are strongly carbon enriched, and tend to
      dewet the tube, in a perpendicular growth mode. Cross-checking our results with
      the available reports from the literature of the last decade strongly suggests
      that these latter conditions should favor the near armchair chiral selectivity
      observed empirically.

PMID- 29589850
TI  - Reconstituting donor T cells increase their biomass following hematopoietic stem
      cell transplantation.
AB  - In this study, we used a rapid, highly-sensitive, single-cell biomass measurement
      method, Live Cell Interferometry (LCI), to measure biomass in populations of CD3
      + T cells isolated from hematopoietic stem cell transplant (SCT) patients at
      various times pre- and post-transplant (days 0-100). CD3 + T cell 'mass spectra'
      were obtained from five autologous and 20 allogenic transplant recipients. We
      found a pronounced rise in median T cell biomass (+25%; p <0.001) shortly after
      transplant (day 14), which moderated by day 60. Further, the inter-patient and
      intra-patient cell masses were most variable at days 14 and 30 post-transplant. T
      cell biomass trends were similar in both autologous and allogenic transplant
      recipients. These data suggest that T cell biomass changes are associated with
      immune reconstitution occurring in the first few weeks post-transplant. To our
      knowledge, this is the first time single-cell biomass measurements have been
      studied in human clinical trials. With refinement, these data may prove useful in
      guiding the withdrawal of immunosuppression following SCT, reducing the
      likelihood of Graft-Versus-Host Disease or cancer relapse occurring.

PMID- 29589851
TI  - Fluidized bed reaction towards crystalline embedded amorphous Si anode with much
      enhanced cycling stability.
AB  - A facile and large-scale fluidized bed reaction route was introduced for the
      first time to prepare crystalline embedded amorphous silicon nanoparticles with
      an average size of 50 nm as anode materials for lithium-ion batteries. By
      increasing the operating potential to control the electrochemically active
      degree, the resulting sample showed excellent cycle stability with a high
      capacity retention of 94.7% after 200 cycles at 1 A g-1 in the voltage range of
      0.12-2.00 V.

PMID- 29589855
TI  - Aerial dioxygen activation vs. thiol-ene click reaction within a system.
AB  - Markovnikov or anti-Markovnikov selective thiol-ene click (TEC) reactions and the
      synthesis of beta-hydroxysulfides via aerial dioxygen activation are prevalent C
      S bond forming reactions of styrenes and thiophenols. Herein, by choosing
      appropriate environments using solvents with additives or neat conditions, any
      one of these three reactions was achieved exclusively in excellent yields.

PMID- 29589856
TI  - Probing the mechanism of thermally driven thiol-Michael dynamic covalent
      chemistry.
AB  - The kinetics and mechanism of the thermally activated dynamic covalent exchange
      of thiol-Michael adducts is investigated. A model system of thiol-Michael adducts
      between thiophenol and phenylvinylketone derivatives and adducts between 2
      mercaptoethanol phenylvinylketone derivatives in N,N-dimethylformamide (DMF) at
      elevated temperatures is used to probe the underlying exchange mechanism. The
      kinetic data show negligible free Michael acceptor, which is consistent with the
      highly efficient thiol-Michael reaction being a "click"-like reaction that
      significantly favors the adduct form. At elevated temperatures of 90  degrees C
      in DMF the thiol-Michael adducts reach equilibrium after 24 h, although
      equilibration did not occur within 24 h at 60  degrees C or 75  degrees C, and
      negligible exchange occurs under ambient conditions. A kinetic model was
      developed to describe the dynamic covalent exchange and equilibration. The
      experimental and simulation kinetic data of dynamic covalent exchange are
      consistent with the thiol-Michael adducts undergoing a retro-Michael reaction,
      followed by subsequent addition of a free thiol to the liberated Michael
      acceptor. Kinetic analysis is consistent with the fragmentation, or retro-Michael
      reaction, being the rate-determining step in the dynamic covalent exchange. This
      suggests that the key step in dynamic covalent exchange is not enhanced by
      addition of free thiol or free Michael acceptor, since the addition reaction is
      much faster than the retro-Michael reaction. This fundamental study will guide
      the design of organic compounds, materials, and bioconjugates that utilize the
      thermally activated dynamic covalent thiol-Michael linkages.

PMID- 29589857
TI  - Concentration-induced multi-colored emissions in carbon dots: origination from
      triple fluorescent centers.
AB  - Color-tunable carbon dots have been synthesized via a one pot hydrothermal
      synthesis and re-dispersed in dimethylformamide solution after purification.
      Structural and optical property characterizations indicate that the concentration
      dependent photoluminescent properties can be ascribed to the existence of multi
      emissive centers in the carbon dots from core states, edge states and surface
      states. Therefore, a multi-center fluorescent mechanism for the carbon dots has
      been proposed according to the preservation effect and inductive effect of the
      solvent. The emission wavelength of the carbon dots with different concentrations
      can be tuned from 585 to 514 nm under the fixed excitation of 420 nm blue light,
      and a warm white light-emitting diode with a CIE color coordinate at (0.42, 0.35)
      is fabricated on a InGaN blue chip emitting 420 nm blue light.

PMID- 29589859
TI  - Preparation of a photo- and thermo-responsive topological gel from anthracene
      modified polyrotaxanes.
AB  - A topological gel was formed from anthracene-modified polyrotaxanes (An-PRs)
      under UV irradiation, and the gel can turn back to a sol under thermal treatment
      due to the dimerization between the anthracene units and the dissociation of the
      formed dimer.

PMID- 29589860
TI  - Seedless assembly of colloidal crystals by inverted micro-fluidic pumping.
AB  - We propose a simple seedless approach to assemble millimeter sized monolayer
      single colloidal crystals with desired orientations at predetermined locations on
      an unstructured charged substrate. This approach utilizes the millimeter-ranged
      fluid flow on the bottom glass substrate induced by an ion exchange resin (IEX)
      fixed on top of the closed sample cell. The fluid flow increases with decreasing
      height of the sample cell and increasing radius R of the IEX. For a single
      inverted pump, millimeter sized monolayer single crystals of hexagonal close
      packing can be obtained. For two closely spaced (D ~ 4R) pumps, the formed
      crystals have a predefined orientation along the line connecting the two IEX. By
      patterning IEX into different structures, colloidal crystals of different complex
      patterns form. The present method paves a convenient way for fabricating high
      quality monolayer colloidal crystals for a variety of applications.

PMID- 29589862
TI  - Tailored dimensionality to regulate the phase stability of inorganic cesium lead
      iodide perovskites.
AB  - Inorganic CsPbI3 perovskites have shown promising potential for achieving all
      inorganic photovoltaic (PV) devices. However, the black perovskite polymorph
      (alpha-phase) of CsPbI3 easily converts into yellow colour (delta-phase) in an
      ambient environment and it is only stable at high temperature (above 320  degrees
      C), which limits its practical application. Here we tailor the three-dimensional
      CsPbI3 perovskite into quasi-two-dimension through adding a large radius cation
      phenylethylammonium (PEA+). The incorporation of PEA+ into the CsPbI3 perovskite
      significantly improves the film morphology as well as the phase stability. An
      optimal CsxPEA1-xPbI3 perovskite film remains stable in the alpha-phase from room
      temperature to 250  degrees C in air and yields a power conversion efficiency of
      5.7% for its solar device. The concept of using large radius cations in the 3D
      perovskite system provides a new perspective to further enhance the phase
      stability while retaining the device performance.

PMID- 29589863
TI  - Macrocycles containing 1,1'-ferrocenyldiselenolato ligands on group 4
      metallocenes.
AB  - Macrocyclic [Fe(eta5-C5H4Se)2M(eta5-C5H4R)2]2 [M = Ti (1), Zr (2), Hf (3), R = H;
      and M = Zr (4), Hf (5), R = tBu] were prepared and characterized by 77Se NMR
      spectroscopy and the crystal structures of 1-3 and 5 were determined by single
      crystal X-ray diffraction. The crystal structure of 4 is known and the complex is
      isomorphous with 5. 1-5 form mutually similar macrocyclic tetranuclear complexes
      in which the alternating Fe(C5H4Se)2 and M(C5H4R)2 centers are linked by selenium
      bridges. The thermogravimetric analysis (TGA) of 1-3 under a helium atmosphere
      indicated that the complexes undergo a two-step decomposition upon heating. The
      final products were identified using powder X-ray diffraction as FexMSe2,
      indicating their potential as single-source precursors for functional materials.

PMID- 29589865
TI  - Hypophosphite hybrid perovskites: a platform for unconventional tilts and shifts.
AB  - Following the recent discovery of the [A]Mn(H2POO)3 (H2POO- = hypophosphite)
      perovskite family, we report the A = [NH2(CH3)2]+ (dimethylammonium, DMA) member.
      This phase shows an unusually large unit cell due to the position of the A-site
      cation within the perovskite cage windows rather than the centre, as is the norm.
      We discuss the tendency of the hypophosphite perovskite skeleton to accommodate
      differently shaped A-site cations through the generation of unconventional tilts
      and columnar shifts, then enumerate these tilts and shifts for all known
      [A]Mn(H2POO)3 phases.

PMID- 29589866
TI  - Glutathione-induced amino-activatable micellar photosensitization platform for
      synergistic redox modulation and photodynamic therapy.
AB  - In recent years, photodynamic therapy (PDT) was considered to be a promising
      cancer treatment modality, however, the therapeutic efficiency was often
      attenuated by the intrinsic antioxidant defense systems. Herein, a kind of novel
      glutathione-induced amino-activatable micelle was designed, which was expected to
      weaken the antioxidant capacity and in the meantime release the photosensitizer
      by the exhaustion of intracellular glutathione (GSH). The amphiphilic
      poly(ethylene glycol)-(2-((2,4-dinitro-N-(ethyl) phenyl)sulfonamido) ethyl
      methacrylate) copolymers were synthesized and assembled into a core-shell nano
      structure in aqueous media. The nano structure demonstrated high sensitivity and
      selectivity to bio-thiols in vitro and in vivo. Subsequently, pheophorbide a
      (PhA) was encapsulated as the model photosensitizer. Upon internalization by
      HepG2 cells, the strongly electron-withdrawing 2,4-dinitrobenzenesulfonyl groups
      on the PADEE segments were readily cleaved by GSH, during which time the
      secondary amino groups (pKb = 11.32) were recovered and completely protonated,
      leading to disassembly of the micelles and rapid release of PhA. Importantly, the
      consumption of GSH weakened the intracellular antioxidant capacity, resulting in
      the synergetic accumulation of reactive oxygen species (ROS) under laser
      irradiation. As a result, this micellar photosensitization system could overcome
      the antioxidant capacity of advanced stage tumors through a simultaneous
      extrinsic and intrinsic strategy, facilitating therapeutic efficiency. These
      results demonstrate that the as-designed micelles provide a versatile
      photosensitization platform for on-demand PDT.

PMID- 29589867
TI  - Luminescent ionic liquids based on cyclometalated platinum(ii) complexes
      exhibiting thermochromic behaviour in different colour regions.
AB  - Luminescent ionic liquids, based on anionic Pt(ii) complexes, were developed.
      Depending on the cyclometalating ligands used, they exhibit thermochromic
      luminescence with different colours. The chromic properties in the flexible
      liquid and glass states emerge through the self-assembling character of the
      square-planar Pt(ii) complexes.

PMID- 29589871
TI  - Temporal dynamics of circadian phase shifting response to consecutive night
      shifts in healthcare workers: role of light-dark exposure.
AB  - KEY POINTS: Shift work is highly prevalent and is associated with significant
      adverse health impacts. There is substantial inter-individual variability in the
      way the circadian clock responds to changing shift cycles. The mechanisms
      underlying this variability are not well understood. We tested the hypothesis
      that light-dark exposure is a significant contributor to this variability; when
      combined with diurnal preference, the relative timing of light exposure accounted
      for 71% of individual variability in circadian phase response to night shift
      work. These results will drive development of personalised approaches to manage
      circadian disruption among shift workers and other vulnerable populations to
      potentially reduce the increased risk of disease in these populations. ABSTRACT:
      Night shift workers show highly variable rates of circadian adaptation. This
      study examined the relationship between light exposure patterns and the magnitude
      of circadian phase resetting in response to night shift work. In 21 participants
      (nursing and medical staff in an intensive care unit) circadian phase was
      measured using 6-sulphatoxymelatonin at baseline (day/evening shifts or days off)
      and after 3-4 consecutive night shifts. Daily light exposure was examined
      relative to individual circadian phase to quantify light intensity in the phase
      delay and phase advance portions of the light phase response curve (PRC). There
      was substantial inter-individual variability in the direction and magnitude of
      phase shift after three or four consecutive night shifts (mean phase delay -1:08
      +/- 1:31 h; range -3:43 h delay to +3:07 h phase advance). The relative
      difference in the distribution of light relative to the PRC combined with diurnal
      preference accounted for 71% of the variability in phase shift. Regression
      analysis incorporating these factors estimated phase shift to within +/-60 min in
      85% of participants. No participants met criteria for partial adaptation to night
      work after three or four consecutive night shifts. Our findings provide evidence
      that the phase resetting that does occur is based on individual light exposure
      patterns relative to an individual's baseline circadian phase. Thus, a 'one size
      fits all' approach to promoting adaptation to shift work using light therapy,
      implemented without knowledge of circadian phase, may not be efficacious for all
      individuals.

PMID- 29589873
TI  - Cost-effectiveness of hydromorphone for severe opioid use disorder: findings from
      the SALOME randomized clinical trial.
AB  - BACKGROUND AND AIMS: Previous research has found diacetylmorphine, delivered
      under supervision, to be cost-effective in the treatment of severe opioid use
      disorder, but diacetylmorphine is not available in many settings. The Study to
      Assess Long-term Opioid Maintenance Effectiveness (SALOME) randomized controlled
      trial provided evidence that injectable hydromorphone is non-inferior to
      diacetylmorphine. The current study aimed to compare the cost-effectiveness of
      hydromorphone directly with diacetylmorphine and indirectly with methadone
      maintenance treatment. DESIGN: A within-trial analysis was conducted using the
      patient level data from the 6-month, double-blind, non-inferiority SALOME trial.
      A life-time analysis extrapolated costs and outcomes using a decision analytical
      cohort model. The model incorporated data from a previous trial to include an
      indirect comparison to methadone maintenance. SETTING: A supervised clinic in
      Vancouver, British Columbia, Canada. PARTICIPANTS: A total of 202 long-term
      street opioid injectors who had at least two attempts at treatment, including one
      with methadone (or other substitution), were randomized to hydromorphone (n =
      100) or diacetylmorphine (n = 102). MEASUREMENTS: We measured the utilization of
      drugs, visits to health professionals, hospitalizations, criminal activity,
      mortality and quality of life. This enabled us to estimate incremental costs,
      quality-adjusted life years (QALYs) and cost-effectiveness ratios from a societal
      perspective. Sensitivity analyses considered different sources of evidence,
      assumptions and perspectives. FINDINGS: The within-trial analysis found
      hydromorphone provided similar QALYs to diacetylmorphine [0.377, 95% confidence
      interval (CI) = 0.361-0.393 versus 0.375, 95% CI = 0.357-0.391], but accumulated
      marginally greater costs [$49 830 ($28 401-73 637) versus $34 320 ($21 780-55
      998)]. The life-time analysis suggested that both diacetylmorphine and
      hydromorphone provide more benefits than methadone [8.4 (7.4-9.5) and 8.3 (7.2
      9.5) versus 7.4 (6.5-8.3) QALYs] at lower cost [$1.01 million ($0.6-1.59 million)
      and $1.02 million ($0.72-1.51 million) versus $1.15 million ($0.71-1.84
      million)]. CONCLUSIONS: In patients with severe opioid use disorder enrolled into
      the SALOME trial, injectable hydromorphone provided similar outcomes to
      injectable diacetylmorphine. Modelling outcomes during a patient's life-time
      suggested that injectable hydromorphone might provide greater benefit than
      methadone alone and may be cost-saving, with drug costs being offset by costs
      saved from reduced involvement in criminal activity.

PMID- 29589872
TI  - Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and
      Abrogates Potency to Ameliorate Ischemia.
AB  - Cigarette smoking (CS) adversely affects the physiologic function of endothelial
      progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on
      the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and
      rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC
      from nonsmokers (nCS-ASC) and smokers (CS-ASC), and their activity to promote
      perfusion in hindlimb ischemia models, as well as endothelial cell (EC) survival
      and vascular morphogenesis in vitro were assessed. While nCS-ASC improved
      perfusion in ischemic limbs, CS-ASC completely lost this therapeutic effect. In
      vitro vasculogenesis assays revealed that human CS-ASC and ASC from CS-exposed
      mice showed compromised support of EC morphogenesis into vascular tubes, and the
      CS-ASC secretome was less potent in supporting EC survival/proliferation.
      Comparative secretome analysis revealed that CS-ASC produced lower amounts of
      hepatocyte growth factor (HGF) and stromal cell-derived growth factor 1 (SDF-1).
      Conversely, CS-ASC secreted the angiostatic/pro-inflammatory factor Activin A,
      which was not detected in nCS-ASC conditioned media (CM). Furthermore, higher
      Activin A levels were measured in EC/CS-ASC cocultures than in EC/nCS-ASC
      cocultures. CS-ASC also responded to inflammatory cytokines with 5.2-fold
      increase in Activin A secretion, whereas nCS-ASC showed minimal Activin A
      induction. Supplementation of EC/CS-ASC cocultures with nCS-ASC CM or with
      recombinant vascular endothelial growth factor, HGF, or SDF-1 did not rescue
      vasculogenesis, whereas inhibition of Activin A expression or activity improved
      network formation up to the level found in EC/nCS-ASC cocultures. In conclusion,
      ASC of CS individuals manifest compromised in vitro vasculogenic activity as well
      as in vivo therapeutic activity. Stem Cells 2018;36:856-867.

PMID- 29589875
TI  - Evidence-based medicine - 2018. Quo Vadis?

PMID- 29589874
TI  - Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High
      Adenosine-Releasing Capacity.
AB  - As a powerful regulator of cellular homeostasis and metabolism, adenosine is
      involved in diverse neurological processes including pain, cognition, and memory.
      Altered adenosine homeostasis has also been associated with several diseases such
      as depression, schizophrenia, or epilepsy. Based on its protective properties,
      adenosine has been considered as a potential therapeutic agent for various brain
      disorders. Since systemic application of adenosine is hampered by serious side
      effects such as vasodilatation and cardiac suppression, recent studies aim at
      improving local delivery by depots, pumps, or cell-based applications. Here, we
      report on the characterization of adenosine-releasing human embryonic stem cell
      derived neuroepithelial stem cells (long-term self-renewing neuroepithelial stem
      [lt-NES] cells) generated by zinc finger nuclease (ZFN)-mediated knockout of the
      adenosine kinase (ADK) gene. ADK-deficient lt-NES cells and their differentiated
      neuronal and astroglial progeny exhibit substantially elevated release of
      adenosine compared to control cells. Importantly, extensive adenosine release
      could be triggered by excitation of differentiated neuronal cultures, suggesting
      a potential activity-dependent regulation of adenosine supply. Thus, ZFN-modified
      neural stem cells might serve as a useful vehicle for the activity-dependent
      local therapeutic delivery of adenosine into the central nervous system. Stem
      Cells Translational Medicine 2018;7:477-486.

PMID- 29589876
TI  - Complex adaptive systems approaches in health care-A slow but real emergence?

PMID- 29589877
TI  - An observational study of benzodiazepine prescription during inpatient alcohol
      detoxification for patients with versus without chronic pretreatment with high
      dosage baclofen.

PMID- 29589878
TI  - Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients:
      Results of a prospective, nationwide study.
AB  - BACKGROUND: Recent data suggest that alcohol-related hepatocellular carcinoma
      (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC
      characteristics and outcomes in an alcohol-related group (group A) and a non
      alcohol-related group (group NA). METHODS: A total of 1207 patients with newly
      diagnosed HCC were prospectively included between May 2008 and October 2009.
      Patients with multiple causes (alcohol plus another cause) were excluded.
      Patients were followed every year for 5 years. Recorded variables, including
      etiologies were tested as prognostic factors of survival in a multivariate Cox
      model after adjustments for a lead-time bias. RESULTS: In all, 894 patients were
      analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol
      related HCC was more likely to be diffuse and detected in patients with a worse
      performance status and worse liver function. After adjustments for a lead-time
      bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A,
      respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol
      non-abstinent groups, respectively (P = .09). The prognostic role of alcohol
      disappeared when survival was assessed at each Barcelona Clinic Liver Cancer
      (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n
      = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in
      comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P <
      .0001). CONCLUSIONS: In comparison with patients with non-alcohol-related HCC,
      patients with alcohol-related HCC have reduced OS, mainly because of worse liver
      function and tumor characteristics at diagnosis, as attested by similar survival
      within each BCLC stage. Cancer 2018;124:1964-72. (c) 2018 American Cancer
      Society.

PMID- 29589879
TI  - Air Pollution and Breast Cancer in Postmenopausal Women: Evidence across Cohorts.

PMID- 29589895
TI  - Graphene Oxide-A Tool for the Preparation of Chemically Crosslinking Free
      Alginate-Chitosan-Collagen Scaffolds for Bone Tissue Engineering.
AB  - Developing a biodegradable scaffold remains a major challenge in bone tissue
      engineering. This study was aimed at developing novel alginate-chitosan-collagen
      (SA-CS-Col)-based composite scaffolds consisting of graphene oxide (GO) to enrich
      porous structures, elicited by the freeze-drying technique. To characterize
      porosity, water absorption, and compressive modulus, GO scaffolds (SA-CS-Col-GO)
      were prepared with and without Ca2+-mediated crosslinking (chemical crosslinking)
      and analyzed using Raman, Fourier transform infrared (FTIR), X-ray diffraction
      (XRD), and scanning electron microscopy techniques. The incorporation of GO into
      the SA-CS-Col matrix increased both crosslinking density as indicated by the
      reduction of crystalline peaks in the XRD patterns and polyelectrolyte ion
      complex as confirmed by FTIR. GO scaffolds showed increased mechanical properties
      which were further increased for chemically crosslinked scaffolds. All scaffolds
      exhibited interconnected pores of 10-250 MUm range. By increasing the
      crosslinking density with Ca2+, a decrease in the porosity/swelling ratio was
      observed. Moreover, the SA-CS-Col-GO scaffold with or without chemical
      crosslinking was more stable as compared to SA-CS or SA-CS-Col scaffolds when
      placed in aqueous solution. To perform in vitro biochemical studies, mouse
      osteoblast cells were grown on various scaffolds and evaluated for cell
      proliferation by using MTT assay and mineralization and differentiation by
      alizarin red S staining. These measurements showed a significant increase for
      cells attached to the SA-CS-Col-GO scaffold compared to SA-CS or SA-CS-Col
      composites. However, chemical crosslinking of SA-CS-Col-GO showed no effect on
      the osteogenic ability of osteoblasts. These studies indicate the potential use
      of GO to prepare free SA-CS-Col scaffolds with preserved porous structure with
      elongated Col fibrils and that these composites, which are biocompatible and
      stable in a biological medium, could be used for application in engineering bone
      tissues.

PMID- 29589896
TI  - New Ablation-Resistant Material Candidate for Hypersonic Applications: Synthesis,
      Composition, and Oxidation Resistance of HfIr3-Based Solid Solution.
AB  - The peculiarities of the solid-state interaction in the HfC-Ir system have been
      studied within the 1000-1600  degrees C temperature range using a set of modern
      analytical techniques. It was stated that the interaction of HfC with iridium
      becomes noticeable at temperatures as low as 1000-1100  degrees C and results in
      the formation of HfIr3-based substitutional solid solution. The homogeneity range
      of the HfIr3+/- x phase was evaluated and refined as HfIr2.43-HfIr3.36. The
      durability of the HfIr3-based system under extreme environmental conditions was
      studied. It was shown that the HfIr3-based material displays excellent ablation
      resistance under extreme environmental conditions. The benefits of the new
      designed material result from its relative oxygen impermeability and special
      microstructure similar to superalloys. The results obtained in this work allow us
      to consider HfIr3 as a very promising candidate for extreme applications.

PMID- 29589898
TI  - Excellent Activity and Selectivity of One-Pot Synthesized Cu-SSZ-13 Catalyst in
      the Selective Catalytic Oxidation of Ammonia to Nitrogen.
AB  - One-pot synthesized Cu-SSZ-13 catalyst treated with dilute HNO3 achieved superior
      activity and selectivity in the selective catalytic oxidation (SCO) of NH3 to
      nitrogen, in comparison with other zeolite-based catalysts and most of metal
      oxide catalysts. Furthermore, the catalyst showed the similar or even higher
      catalytic activity than the partial noble-metal catalysts, and meanwhile its N2
      selectivity was superior to most noble-metal catalysts. The characterization
      results demonstrated that more Cu2+ ions existing in Cu-SSZ-13 catalyst were
      advantageous to its NH3-SCO activity. The in situ DRIFTS results indicated that
      the reactivity of NH3 species adsorbed on Lewis and Bronsted acid sites over Cu
      SSZ-13-O-H catalyst depended on the reaction temperature. The results of this
      study suggest the one-pot synthesized Cu-SSZ-13 is a promising NH3-SCO catalyst
      for practical application, either mobile or stationary pollution sources.

PMID- 29589897
TI  - Magnetic Nanotweezers for Interrogating Biological Processes in Space and Time.
AB  - The ability to sense and manipulate the state of biological systems has been
      extensively advanced during the past decade with the help of recent developments
      in physical tools. Unlike standard genetic and pharmacological perturbation
      techniques-knockdown, overexpression, small molecule inhibition-that provide a
      basic on/off switching capability, these physical tools provide the capacity to
      control the spatial, temporal, and mechanical properties of the biological
      targets. Among the various physical cues, magnetism offers distinct advantages
      over light or electricity. Magnetic fields freely penetrate biological tissues
      and are already used for clinical applications. As one of the unique features,
      magnetic fields can be transformed into mechanical stimuli which can serve as a
      cue in regulating biological processes. However, their biological applications
      have been limited due to a lack of high-performance magnetism-to-mechanical force
      transducers with advanced spatiotemporal capabilities. In this Account, we
      present recent developments in magnetic nanotweezers (MNTs) as a useful tool for
      interrogating the spatiotemporal control of cells in living tissue. MNTs are
      composed of force-generating magnetic nanoparticles and field generators. Through
      proper design and the integration of individual components, MNTs deliver
      controlled mechanical stimulation to targeted biomolecules at any desired space
      and time. We first discuss about MNT configuration with different force
      stimulation modes. By modulating geometry of the magnetic field generator, MNTs
      exert pulling, dipole-dipole attraction, and rotational forces to the target
      specifically and quantitatively. We discuss the key physical parameters
      determining force magnitude, which include magnetic field strength, magnetic
      field gradient, magnetic moment of the magnetic particle, as well as distance
      between the field generator and the particle. MNTs also can be used over a wide
      range of biological time scales. By simply adjusting the amplitude and phase of
      the applied current, MNTs based on electromagnets allow for dynamic control of
      the magnetic field from microseconds to hours. Chemical design and the nanoscale
      effects of magnetic particles are also essential for optimizing MNT performance.
      We discuss key strategies to develop magnetic nanoparticles with improved force
      generation capabilities with a particular focus on the effects of size, shape,
      and composition of the nanoparticles. We then introduce various strategies and
      design considerations for target-specific biomechanical stimulations with MNTs.
      One-to-one particle-receptor engagement for delivering a defined force to the
      targeted receptor and the small size of the nanoparticles are important. Finally,
      we demonstrate the utility of MNTs for manipulating biological functions and
      activities with various spatial (single molecule/cell to organisms) and temporal
      resolution (microseconds to days). MNTs have the potential to be utilized in many
      exciting applications across diverse biological systems spanning from fundamental
      biology investigations of spatial and mechanical signaling dynamics at the single
      cell and systems levels to in vivo therapeutic applications.

PMID- 29589899
TI  - Broadband and Lightweight Microwave Absorber Constructed by in Situ Growth of
      Hierarchical CoFe2O4/Reduced Graphene Oxide Porous Nanocomposites.
AB  - A broadband and lightweight microwave absorber has attracted soaring research
      interest because of the increasing demand for electronic reliability and defense
      security. Lightweight ferrites/graphene porous composites with abundant
      interfaces are potential high-performance absorbers owing to their balanced
      attenuation ability and impedance matching. Herein, we synthesized hierarchical
      CoFe2O4/reduced graphene oxide (CFO/rGO) nanocomposites with a porous structure
      via an in situ solvothermal method. The electromagnetic parameters of CFO/rGO
      nanocomposites can be well-adjusted by modulating the weight fraction of rGO. The
      hierarchical porous structure and proper electromagnetic parameters result in the
      enhancement of impedance matching and attenuation ability. Benefiting from the
      controllable composition, hierarchical porous structure, and strong synergetic
      effect between CFO and rGO sheets, as expected, CFO/rGO nanocomposites exhibit
      superior microwave absorption performance with an ultrabroad bandwidth reaching
      5.8 GHz (8.3-14.1 GHz) with a thin thickness of 2.8 mm. Meanwhile, a strong
      reflection loss of -57.7 dB at the same thickness is achieved. Considering the
      outstanding microwave absorption performance, the hierarchical CFO/rGO porous
      nanocomposites can be employed as a high-performance microwave absorber.

PMID- 29589900
TI  - Cooperative Catechol-Functionalized Polypept(o)ide Brushes and Ag Nanoparticles
      for Combination of Protein Resistance and Antimicrobial Activity on Metal Oxide
      Surfaces.
AB  - Prevention of biofouling and microbial contamination of implanted biomedical
      devices is essential to maintain their functionality and biocompatibility. For
      this purpose, polypept(o)ide block copolymers have been developed, in which a
      protein-resistant polysarcosine (pSar) block is combined with a dopamine-modified
      poly(glutamic acid) block for surface coating and silver nanoparticles (Ag NPs)
      formation. In the development of a novel, versatile, and biocompatible
      antibacterial surface coating, block lengths pSar were varied to derive structure
      property relationships. Notably, the catechol moiety performs two important tasks
      in parallel; primarily it acts as an efficient anchoring group to metal oxide
      surfaces, while it furthermore induces the formation of Ag NPs. Attributing to
      the dual function of catechol moieties, antifouling pSar brush and antimicrobial
      Ag NPs can not only adhere stably on metal oxide surfaces, but also display
      passive antifouling and active antimicrobial activity, showing good
      biocompatibility simultaneously. The developed strategy seems to provide a
      promising platform for functional modification of biomaterials surface to
      preserve their performance while reducing the risk of bacterial infections.

PMID- 29589902
TI  - Nanoscale Investigations of alpha- and gamma-Crystal Phases in PVDF-Based
      Nanocomposites.
AB  - The impact of carbon nanotube (CNT) incorporation into semicrystalline
      poly(vinylidene fluoride), PVDF, was investigated at both the macro and
      nanoscales. A special effort was devoted to probe the local morphology and the
      mechanical, ferroelectric, piezoelectric, and electrical conductivity response by
      means of atomic force microscopy. Incorporation of CNTs mainly induces the
      development of the polar gamma-phase, and as a consequence, the coexistence of
      the gamma-phase with the most stable nonpolar alpha-phase is observed. A maximum
      gamma-phase content is reached at 0.7 wt % CNT loading. The spherulitic
      morphology of the PVDF alpha-phase is assessed, in conjunction with the lack of
      any ferroelectric response, while the presence of the polar gamma-phase is
      confirmed, owing to clear piezoresponse signals. Local piezoelectric measurements
      on gamma-phase domains yield a maximum effective coefficient | d33| ~ 13 pm/V,
      thus underlining the potential for applications of such functional PVDF-based
      nanocomposites in advanced piezoelectric devices. An increase in macroscopic
      conductivity with CNT content is observed, with a percolation threshold achieved
      for a composition close to 0.7 wt %. Nanoscale investigation of the electrical
      conductivity confirms the presence of some infinite CNT cluster homogeneously
      distributed over the surface. The macroscopic viscoelastic behavior of the
      composite reflects the reinforcing effect of CNTs, while the nanomechanical
      characterization yields a local contact modulus of the gamma-phase domains larger
      than that of its alpha-phase counterpart, in agreement with the fact that the
      CNTs act as gamma-phase promoters and subsequently reinforce the gamma-domains.

PMID- 29589903
TI  - Changes in Protein Dynamics in Escherichia coli SufS Reveal a Possible Conserved
      Regulatory Mechanism in Type II Cysteine Desulfurase Systems.
AB  - In the Suf Fe-S cluster assembly pathway, the activity of the cysteine
      desulfurase, SufS, is regulated by interactions with the accessory
      sulfotransferase protein, SufE. SufE has been shown to stimulate SufS activity,
      likely by inducing conformational changes in the SufS active site that promote
      the desulfurase step and by acting as an efficient persulfide acceptor in the
      transpersulfuration step. Previous results point toward an additional level of
      regulation through a "half-sites" mechanism that affects the stoichiometry and
      affinity for SufE as the dimeric SufS shifts between desulfurase and
      transpersulfuration activities. Investigation of the covalent persulfide
      intermediate of SufS by backbone amide hydrogen-deuterium exchange mass
      spectrometry identified two active site peptides (residues 225-236 and 356-366)
      and two peptides at the dimer interface of SufS (residues 88-100 and 243-255)
      that exhibit changes in deuterium uptake upon formation of the intermediate.
      Residues in these peptides are organized to form a conduit between the two active
      sites upon persulfide formation and include key cross-monomer interactions,
      suggesting they may play a role in the half-sites regulation. Three
      evolutionarily conserved residues at the dimer interface (R92, E96, and E250)
      were investigated by alanine scanning mutagenesis. Two of the substituted enzymes
      (E96A and E250A SufS) resulted in 6-fold increases in the value of KSufE,
      confirming a functional role. Re-examination of the dimer interface in reported
      crystal structures of SufS and the SufS homologue CsdA identified previously
      unnoticed residue mobility at the dimer interface. The identification of
      conformational changes at the dimer interface by hydrogen-deuterium exchange
      confirmed by mutagenesis and structural reports provides a physical mechanism for
      active site communication in the half-sites regulation of SufS activity. Given
      the conservation of the interface interactions, this mechanism may be broadly
      applicable to type II cysteine desulfurase systems.

PMID- 29589901
TI  - Mini-Review: Ergothioneine and Ovothiol Biosyntheses, an Unprecedented Trans
      Sulfur Strategy in Natural Product Biosynthesis.
AB  - As one of the most abundant elements on earth, sulfur is part of many small
      molecular metabolites and is key to their biological activities. Over the past
      few decades, some general strategies have been discovered for the incorporation
      of sulfur into natural products. In this review, we summarize recent efforts in
      elucidating the biosynthetic details for two sulfur-containing metabolites,
      ergothioneine and ovothiol. Their biosyntheses involve an unprecedented trans
      sulfur strategy, a combination of a mononuclear non-heme iron enzyme-catalyzed
      oxidative C-S bond formation reaction and a PLP enzyme-mediated C-S lyase
      reaction.

PMID- 29589904
TI  - Engineering a Dual Small Molecule Gated ZAP70 Switch in T Cells.
AB  - T cells expressing tumor-specific T cell receptors are promising cancer
      therapeutic agents, but safety control switches are needed to manage potential
      side effects arising from overactivity. Here, we present the first dual small
      molecule-gated ZAP70 signaling switch for the regulation of T cell activity. We
      show that when an analogue-sensitive ZAP70 allele is fused to the engineered
      ligand binding domain of the estrogen receptor, ERT2, its activity can be
      upregulated to an extent by a metabolite of an FDA-approved tamoxifen, 4-hydroxy
      tamoxifen, and downregulated by an ATP analogue, 3-MB-PP1. The strength of early
      T cell signaling can also be modulated by varying the concentrations of activator
      and inhibitor, and the switch exhibits temporal control on the time scale of
      minutes. Interestingly, the switch has the ability to control CD69 and calcium
      levels in T cells but has limited capabilities in the regulation of downstream
      cytokine release, suggesting further investigation is needed before it can be
      implemented in adoptive T cell therapy.

PMID- 29589905
TI  - Complex Chaperone Dependence of Rubisco Biogenesis.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), a ~530 kDa complex of
      8 large (RbcL) and 8 small subunits (RbcS), mediates the fixation of atmospheric
      CO2 into usable sugars during photosynthesis. Despite its fundamental role,
      Rubisco is a remarkably inefficient enzyme and thus is produced by plants in huge
      amounts. It has long been a key target for bioengineering with the goal to
      increase crop yields. However, such efforts have been hampered by the complex
      requirement of Rubisco biogenesis for molecular chaperones. Recent studies have
      identified an array of auxiliary factors needed for the folding and assembly of
      the Rubisco subunits. The folding of plant RbcL subunits is mediated by the
      cylindrical chloroplast chaperonin, Cpn60, and its cofactor Cpn20. Folded RbcL
      requires a number of additional Rubisco specific assembly chaperones, including
      RbcX, Rubisco accumulation factors 1 (Raf1) and 2 (Raf2), and the Bundle sheath
      defective-2 (BSD2), to mediate the assembly of the RbcL8 intermediate complex.
      Incorporation of the RbcS and displacement of the assembly factors generates the
      active holoenzyme. An Escherichia coli strain expressing the chloroplast
      chaperonin and auxiliary factors now allows the expression of functional plant
      Rubisco, paving the way for Rubisco engineering by large scale mutagenesis. Here,
      we review our current understanding on how these chaperones cooperate to produce
      one of the most important enzymes in nature.

PMID- 29589906
TI  - Long-Range Capture and Delivery of Water-Dispersed Nano-objects by Microbubbles
      Generated on 3D Plasmonic Surfaces.
AB  - The possibility of investigating small amounts of molecules, moieties, or nano
      objects dispersed in solution constitutes a central step for various application
      areas in which high sensitivity is necessary. Here, we show that the rapid
      expansion of a water bubble can act as a fast-moving net for molecules or nano
      objects, collecting the floating objects in the surrounding medium in a range up
      to 100 MUm. Thanks to an engineered 3D patterning of the substrate, the collapse
      of the bubble could be guided toward a designed area of the surface with
      micrometric precision. Thus, a locally confined high density of particles is
      obtained, ready for evaluation by most optical/spectroscopic detection schemes.
      One of the main relevant strengths of the long-range capture and delivery method
      is the ability to increase, by a few orders of magnitude, the local density of
      particles with no changes in their physiological environment. The bubble is
      generated by an ultrafast IR laser pulse train focused on a resonant plasmonic
      antenna; due to the excitation process, the technique is trustworthy and
      applicable to biological samples. We have tested the reliabilities of the process
      by concentrating highly dispersed fluorescence molecules and fluorescent beads.
      Lastly, as an ultimate test, we have applied the bubble clustering method on
      nanosized exosome vesicles dispersed in water; due to the clustering effect, we
      were able to effectively perform Raman spectroscopy on specimens that were
      otherwise extremely difficult to measure.

PMID- 29589907
TI  - Structural Determinants for the Interactions of Chemically Modified Nucleic Acids
      with the Stabilin-2 Clearance Receptor.
AB  - The Stabilin receptors are systemic clearance receptors for some classes of
      chemically modified nucleic acid therapeutics. In this study, the recombinant
      human secreted ecto-domain of the small isoform of Stabilin-2 (s190) was purified
      from cell culture and evaluated for direct binding with a multitude of antisense
      oligonucleotides (ASOs) using a fluorescence polarization-based assay. The tested
      ASOs varied in their backbone composition, modification of the ribose 2'
      position, overall length of the oligo, and sequence of the nucleotide bases. A
      fully phosphorothioate (PS) ASO with a 5-10-5 pattern of flanking 2'- O
      methoxyethyl modifications was then used to test the effects of pH and salt
      concentration on receptor binding. These tests concluded that the PS backbone was
      the primary determinant for ASO binding and that decreasing pH and increasing
      salt generally increased the rate of ligand dissociation and fit within the
      biological parameters expected of a constitutive recycling receptor. These
      results will be useful in the rational design of therapeutic oligonucleotides for
      enhancing their affinity or avoidance of the Stabilin receptors.

PMID- 29589908
TI  - Sophisticated Construction of Binary PdPb Alloy Nanocubes as Robust
      Electrocatalysts toward Ethylene Glycol and Glycerol Oxidation.
AB  - The design of nanocatalysts by controlling pore size and particle characteristics
      is crucial to enhance the selectivity and activity of the catalysts. Thus, we
      have successfully demonstrated the synthesis of binary PdPb alloy nanocubes (PdPb
      NCs) by controlling pore size and particle characteristics. In addition, the as
      obtained binary PdPb NCs exhibited superior electrocatalytic activity of 4.06 A
      mg-1 and 16.8 mA cm-2 toward ethylene glycol oxidation reaction and 2.22 A mg-1
      and 9.2 mA cm-2 toward glycerol oxidation reaction when compared to the
      commercial Pd/C. These astonishing characteristics are attributed to the
      attractive nanocube structures as well as the large number of exposed active
      areas. Furthermore, the bifunctional effects originated from Pd and Pb
      interactions help to display high endurance with less activity decay after 500
      cycles, showing a great potential in fuel cell applications.

PMID- 29589909
TI  - Material-Independent Nanotransfer onto a Flexible Substrate Using Mechanical
      Interlocking Structure.
AB  - Nanowire-transfer technology has received much attention thanks to its capability
      to fabricate high-performance flexible nanodevices with high simplicity and
      throughput. However, it is still challenging to extend the conventional nanowire
      transfer method to the fabrication of a wide range of devices since a chemical
      adhesion-based nanowire-transfer mechanism is complex and time-consuming,
      hindering successful transfer of diverse nanowires made of various materials.
      Here, we introduce a material-independent mechanical-interlocking-based nanowire
      transfer (MINT) method, fabricating ultralong and fully aligned nanowires on a
      large flexible substrate (2.5 * 2 cm2) in a highly robust manner. For the
      material-independent nanotransfer, we developed a mechanics-based nanotransfer
      method, which employs a dry-removable amorphous carbon (a-C) sacrificial layer
      between a vacuum-deposited nanowire and the underlying master mold. The
      controlled etching of the sacrificial layer enables the formation of a mechanical
      interlocking structure under the nanowire, facilitating peeling off of the
      nanowire from the master mold robustly and reliably. Using the developed MINT
      method, we successfully fabricated various metallic and semiconductor nanowire
      arrays on flexible substrates. We further demonstrated that the developed method
      is well suited to the reliable fabrication of highly flexible and high
      performance nanoelectronic devices. As examples, a fully aligned gold (Au)
      microheater array exhibited high bending stability (106 cycling) and ultrafast
      (~220 ms) heating operation up to ~100  degrees C. An ultralong Au heater
      embedded cuprous-oxide (Cu2O) nanowire chemical gas sensor showed significantly
      improved reversible reaction kinetics toward NO2 with 10-fold enhancement in
      sensitivity at 100  degrees C.

PMID- 29589910
TI  - Single-Cell Digital Lysates Generated by Phase-Switch Microfluidic Device Reveal
      Transcriptome Perturbation of Cell Cycle.
AB  - With conventional gene expression profiling, information concerning cellular
      heterogeneity is often lost in the physical mixing and averaging of millions of
      cells. Single-cell transcriptome analysis has the potential to address these
      issues. However, there is a need to determine how many cells are needed to draw
      meaningful conclusions in each single-cell study. Here, we introduce the concept
      of "digital lysate" for assessing cellular heterogeneity with a phase-switch
      microfluidic platform and apply it to construct a molecular map of transcriptome
      perturbation during the cell cycle. Using a phase-switch droplet microfluidic
      platform and next-generation sequencing, we obtained transcriptomes of single
      cells by random sampling. Digital lysates were generated by permutating and
      averaging multiple single-cell transcriptomes. In our studied cell populations,
      digital lysates converged to physical lysates ( r = 0.93), and the sample-to
      sample repeatability was comparable to that of conventional analysis of a
      physical lysate ( r = 0.98). After determining the number of cells needed, single
      cell transcriptomes were used to organize cells into a map by molecular
      similarity, and the map was validated by cell cycle-specific markers ( p =
      0.003). Cell cycle regulatory genes were inferred using this molecular map and
      verified with siRNA assays. The study described here provides an effective
      approach, the generation and analysis of digital lysates, to investigate cellular
      heterogeneity.

PMID- 29589911
TI  - MXene-Based Electrode with Enhanced Pseudocapacitance and Volumetric Capacity for
      Power-Type and Ultra-Long Life Lithium Storage.
AB  - Powerful yet thinner lithium-ion batteries (LIBs) are eagerly desired to meet the
      practical demands of electric vehicles and portable electronic devices. However,
      the use of soft carbon materials in current electrode design to improve the
      electrode conductivity and stability does not afford high volumetric capacity due
      to their low density and capacity for lithium storage. Herein, we report a
      strategy leveraging the MXene with superior conductivity and density to soft
      carbon as matrix and additive material for comprehensively enhancing the power
      capability, lifespan, and volumetric capacity of conversion-type anode. A
      kinetics favorable 2D nanohybrid with high conductivity, compact density,
      accumulated pseudocapacitance, and diffusion-controlled behavior is fabricated by
      coupling Ti3C2 MXene with high-density molybdenum carbide for fast lithium
      storage over 300 cycles with high capacities. By replacing the carbonaceous
      conductive agent with Ti3C2 MXene, the electrodes with better conductivity and
      dramatically reduced thickens could be further manufactured to achieve 37-40%
      improvement in capacity retention and ultra-long life of 5500 cycles with
      extremely slow capacity loss of 0.002% per cycle at high current rates. Ultrahigh
      volumetric capacity of 2460 mAh cm-3 could be attained by such MXene-based
      electrodes, highlighting the great promise of MXene in the development of high
      performance LIBs.

PMID- 29589912
TI  - beta-Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum
      Albumin.
AB  - Perfluorooctanoic acid (PFOA), a persistent organic pollutant known to cause
      adverse health effects, strongly binds to human serum albumin (HSA). beta
      Cyclodextrin (beta-CD), a nontoxic cyclic sugar, strongly complexes PFOA in a
      host-guest complex and has been proposed for environmental remediation of PFOA.
      The interactions between HSA, PFOA, and beta-CD were investigated in order to
      determine if beta-CD can reverse the binding of PFOA to HSA, with potential
      therapeutic applications toward exposure to PFOA. 19F Nuclear magnetic resonance
      (NMR), circular dichroism, and fluorescence spectroscopies were used to study
      these interactions. Multiple PFOA binding sites to HSA, one with strong affinity
      and others with low affinity, are evident from changes in the fluorescence
      emission spectra of HSA and the fluorescence lifetimes of the single Trp residue
      in HSA with increasing PFOA concentration. Structural changes in the protein are
      also evident from changes in the circular dichroism spectra of HSA upon titration
      of PFOA. Addition of beta-CD to PFOA and HSA reversed these changes, indicating
      that formation of the beta-CD:PFOA host-guest complex is favored even in the
      presence of HSA. Equimolar beta-CD to PFOA (1:1 beta-CD:PFOA ratio) causes
      dissociation of the weakly bound PFOA from HSA, whereas excess beta-CD relative
      to PFOA (5:1 beta-CD:PFOA ratio) leads to the complete disassociation of the
      strongly bound PFOA molecule from HSA. The 19F NMR studies further suggest that
      the 2:1 beta-CD:PFOA complex inhibits PFOA binding to HSA. These data demonstrate
      that beta-CD has potential to be used in therapeutic applications for PFOA in
      human blood.

PMID- 29589913
TI  - Extratelomeric Binding of the Telomere Binding Protein TRF2 at the PCGF3 Promoter
      Is G-Quadruplex Motif-Dependent.
AB  - Telomere repeat binding factor 2 (TRF2) is critical for the protection of
      chromosome ends. Mounting evidence suggests that TRF2 associates with
      extratelomeric sites and TRF2 functions may not be limited to telomeres. Here, we
      show that the PCGF3 promoter harbors a sequence capable of forming the DNA
      secondary structure G-quadruplex motif, which is required for binding of TRF2 at
      the PCGF3 promoter. We demonstrate that promoter binding by TRF2 mediates PCGF3
      promoter activity, and both the N-terminal and C-terminal domains of TRF2 are
      necessary for promoter activity. Altogether, this shows for the first time that a
      telomere binding factor may regulate a component of the polycomb group of
      proteins.

PMID- 29589914
TI  - Unravelling the Metabolic Progression of Breast Cancer Cells to Bone Metastasis
      by Coupling Raman Spectroscopy and a Novel Use of Mcr-Als Algorithm.
AB  - Raman spectroscopy (RS) has shown promise as a tool to reveal biochemical changes
      that occur in cancer processes at the cellular level. However, when analyzing
      clinical samples, RS requires improvements to be able to resolve biological
      components from the spectra. We compared the strengths of Multivariate Curve
      Resolution (MCR) versus Principal Component Analysis (PCA) to deconvolve
      meaningful biological components formed by distinct mixtures of biological
      molecules from a set of mixed spectra. We exploited the flexibility of the MCR
      algorithm to easily accommodate different initial estimates and constraints. We
      demonstrate the ability of MCR to resolve undesired background signals from the
      RS that can be subtracted to obtain clearer cancer cell spectra. We used two
      triple negative breast cancer cell lines, MDA-MB 231 and MDA-MB 435, to
      illustrate the insights obtained by RS that infer the metabolic changes required
      for metastasis progression. Our results show that increased levels of amino acids
      and lower levels of mitochondrial signals are attributes of bone metastatic
      cells, whereas lung metastasis tropism is characterized by high lipid and
      mitochondria levels. Therefore, we propose a method based on the MCR algorithm to
      achieve unique biochemical insights into the molecular progression of cancer
      cells using RS.

PMID- 29589915
TI  - Tailoring Interfacial Nanoparticle Organization through Entropy.
AB  - The ability to tailor the interfacial behaviors of nanoparticles (NPs) is crucial
      not only for the design of novel nanostructured materials with superior
      properties and of interest for many promising applications such as water
      purification, enhanced oil recovery, and innovative energy transduction, but also
      for a better insight into many biological systems where nanoscale particles such
      as proteins or viruses can interact and organize at certain interfaces. As a
      class of emerging building blocks, Janus NPs consisting of two compartments of
      different chemistry or polarity are ideal candidates to generate tunable and
      stable interfacial nanostructures because of the asymmetric nature. However,
      precise control over such interfacial nanostructures toward a controllable order
      and even responses to various external stimuli still remains a great challenge as
      the interfaces do not simply serve as a scaffold but rather induce complex
      enthalpic and entropic interactions. In this Account, we focus on our efforts on
      exploiting entropy strategies based on computational design to tailor the spatial
      distribution and ordering of NPs at the interfaces of various systems. First, we
      introduce the physical principle of entropic ordering, being the theoretical
      basis of entropy-directed interfacial self-assembly. The typical types of
      entropy, which have been harnessed to manipulate the interfacial NP organization,
      are then summarized, including conformational entropy, shape entropy, and
      rotational and vibrational entropy. Next, we describe the emerging pathways in
      the development of novel environmentally responsive systems which involve the use
      of entropy to access the stimuli-responsive behaviors of interfacial
      nanostructures. Taking one step further, how molecular architectures can be
      tailored to tune the entropic contributions to the interfacial self-assembly is
      demonstrated, through identifying the effects of various intrinsic properties of
      block segments, such as chain length and stiffness, on entropy-governed precise
      organization of Janus NPs at block copolymer interfaces. Finally, we detail some
      key factors for tailoring interfacial organization through entropy. In summary,
      entropy strategies offer a promising and abundant framework for precisely
      programming the structural organization of NPs at interfaces. We discuss future
      directions to signify the framework in tailoring the interfacial organization of
      NPs. We hope that this Account will promote further efforts toward fundamental
      research and the wide applications of designed interfacial assemblies in new
      types of functional nanomaterials and beyond.

PMID- 29589916
TI  - Designing Helical Molecular Capsules Based on Folded Aromatic Amide Oligomers.
AB  - The ab initio rational structure-based design of a synthetic molecular receptor
      for a given complex biomolecular guest remains an elusive objective, yet
      remarkable progress has been achieved in recent years. This Account deals with
      the use of folded artificial aromatic amide oligomers, also termed aromatic
      foldamers, inspired from biopolymer structures, for the design of helical
      molecular capsules that can recognize guest molecules, completely surround them,
      and isolate them from the solvent, thus giving rise to a sort of guest
      encapsulation associated with slow binding and release kinetics. The development
      of new amino acid, diacid, and diamine monomers, a main source of creativity in
      this field, progress in their assembly into ever longer oligoamide sequences, and
      the predictability of the folded structures due to their inherent rigidity and
      simple folding principles, allowed for the design and preparation of unimolecular
      and bimolecular capsule shapes. These capsules consist of molecular helices
      having a large diameter in the middle and a narrow diameter at both ends thus
      creating a cavity suitable for binding a guest molecule. The understanding of
      molecular recognition properties within these bioinspired containers has greatly
      progressed. Recognition of simple guests such as diols or amino-alcohols may thus
      be predicted, and hosts can be proposed for guests as complex as saccharides
      using first principle design. Taking advantage of the modular nature of
      oligomeric sequences, of their synthetic accessibility and of their propensity to
      grow into crystals suitable for X-ray crystallographic analysis, a structure
      based iterative design methodology has been developed that eventually yielded
      exquisite guest selectivity, affinity, and diastereoselectivity. This methodology
      involves rational negative design steps during which changes in the foldamer
      capsule sequence are not intended to improve binding to the targeted guest but
      instead to exclude the binding of other guests while preserving key interactions
      with the target. Metal ions can also be introduced at the inner rim of foldamer
      capsules and eventually assist the binding of an organic guest. These results
      demonstrate the viability of an ab initio approach to abiotic receptor design
      based on aromatic foldamers. The dynamic of the capsules associated with their
      self-organized nature provides opportunities to not only tune guest binding and
      selectivity, but also guest capture and release kinetics as well as cavity size
      and shape. Controlled release thus emerges as a realistic objective. Recent
      progress thus opens up multiple perspectives for the development of tailored
      hosts, sensors, and carriers structurally and conceptually different from earlier
      generations of macrocyclic-based receptors or from supramolecular containers
      produced by self-assembly.

PMID- 29589917
TI  - Correction to "An Alkyne-Aspirin Chemical Reporter for the Detection of Aspirin
      Dependent Protein Modification in Living Cells".

PMID- 29589919
TI  - Iron-Catalyzed Highly Enantioselective Hydrosilylation of Unactivated Terminal
      Alkenes.
AB  - The iron-catalyzed highly Markovnikov-type selective and enantioselective
      hydrosilylation of terminal aliphatic alkenes with good functional group
      tolerance is developed. This operationally simple protocol uses earth-abundant
      transition metal catalyst, readily available aliphatic alkenes and hydrosilanes
      to construct valuable chiral organosilanes with better than 99% ee in most cases.
      The chiral aliphatic alkan-2-ol and chiral dihydroxysilane as an analogue of
      ketone could be efficiently synthesized via further derivatization of chiral
      organosilanes without any racemization.

PMID- 29589918
TI  - Effects of Hydrophilic Residues and Hydrophobic Length on Flip-Flop Promotion by
      Transmembrane Peptides.
AB  - Peptide-induced phospholipid flip-flop (scrambling) was evaluated using
      transmembrane model peptides in which the central residue was substituted with
      various amino acid residues (sequence: Ac-GKK(LA) nXW(LA) nLKKA-CONH2). Peptides
      with a strongly hydrophilic residue (X = Q, N, or H) had higher scramblase
      activity than that of other peptides, and the activity was also dependent on the
      length of the peptides. Peptides with a hydrophobic stretch of 17 residues showed
      high flip-promotion propensity, whereas those of 21 and 25 residues did not,
      suggesting that membrane thinning under negative mismatch conditions promotes the
      flipping. Interestingly, a hydrophobic stretch of 19 residues intensively
      promoted phospholipid scrambling and membrane leakage. The distinctive
      characteristics of the peptide were ascribed by long-term molecular dynamics
      simulation to the arrangement of central glutamine and terminal four lysine
      residues on the same side of the helix. The combination of simulated and
      experimental data enables understanding of the mechanisms by which transmembrane
      helices, and ultimately unidentified scramblases in biomembranes, cause lipid
      scrambling.

PMID- 29589920
TI  - Case for Lithium Tetramethylpiperidide-Mediated Ortholithiations: Reactivity and
      Mechanisms.
AB  - Rate and mechanistic studies of ortholithiations by lithium 2,2,6,6
      tetramethylpiperidide focus on four arenes: 1,4-bis(trifluoromethyl)benzene, 1,3
      bis(trifluoromethyl)benzene, 1,3-dimethoxybenzene, and 4,4-dimethyl-2-phenyl-2
      oxazoline. Metalations occur via substrate-dependent combinations of monosolvated
      monomer, disolvated monomer, and tetrasolvated dimer (triple ions). Density
      functional theory computational studies augment the experimental data. We discuss
      the challenges presented by shifting dimer-monomer proportions in determining the
      observable reaction orders and our mathematical treatment of such shifting in
      reactant structure.

PMID- 29589921
TI  - A Thermodynamic Model for Redox-Dependent Binding of Carbon Monoxide at Site
      Differentiated, High Spin Iron Clusters.
AB  - Binding of N2 and CO by the FeMo-cofactor of nitrogenase depends on the redox
      level of the cluster, but the extent to which pure redox chemistry perturbs the
      affinity of high spin iron clusters for pi-acids is not well understood. Here, we
      report a series of site-differentiated iron clusters that reversibly bind CO in
      redox states FeII4 through FeIIFeIII3. One electron redox events result in small
      changes in the affinity for (at most ~400-fold) and activation of CO (at most 28
      cm-1 for nuCO). The small influence of redox chemistry on the affinity of these
      high spin, valence-localized clusters for CO is in stark contrast to the large
      enhancements (105-1022 fold) in pi-acid affinity reported for monometallic and
      low spin, bimetallic iron complexes, where redox chemistry occurs exclusively at
      the ligand binding site. While electron-loading at metal centers remote from the
      substrate binding site has minimal influence on the CO binding energetics (~1
      kcal.mol-1), it provides a conduit for CO binding at an FeIII center. Indeed,
      internal electron transfer from these remote sites accommodates binding of CO at
      an FeIII, with a small energetic penalty arising from redox reorganization (~2.6
      kcal.mol-1). The ease with which these clusters redistribute electrons in
      response to ligand binding highlights a potential pathway for coordination of N2
      and CO by FeMoco, which may occur on an oxidized edge of the cofactor.

PMID- 29589922
TI  - Mutagenesis of an Active-Site Loop in Tryptophan Hydroxylase Dramatically Slows
      the Formation of an Early Intermediate in Catalysis.
AB  - Solution studies of the aromatic amino acid hydroxylases are consistent with the
      FeIVO intermediate not forming until both the amino acid and tetrahydropterin
      substrates have bound. Structural studies have shown that the positions of active
      site loops differs significantly between the free enzyme and the enzyme-amino
      acid-tetrahydropterin complex. In tryptophan hydroxylase (TrpH) these mobile
      loops contain residues 124-134 and 365-371, with a key interaction involving
      Ile366. The I366N mutation in TrpH results in decreases of 1-2 orders of
      magnitude in the kcat and kcat/ Km values. Single turnover analyses establish
      that the limiting rate constant for turnover is product release for the wild-type
      enzyme but is formation of the first detectable intermediate I in catalysis in
      the mutant enzyme. The mutation does not alter the kinetics of NO binding to the
      ternary complex nor does it uncouple FeIVO formation from amino acid
      hydroxylation. The effects on the kcat value of wild-type TrpH of changing
      viscosity are consistent with rate-limiting product release. While the effect of
      viscosity on the kcat/ KO2 value is small, consistent with reversible oxygen
      binding, the effects on the kcat/ Km values for tryptophan and the
      tetrahydropterin are large, with the latter value exceeding the expected limit
      and varying with the identity of the viscogen. In contrast, the kinetic
      parameters of I366N TrpH show small changes with viscosity. The results are
      consistent with binding of the amino acid and pterin substrate to form the
      ternary complex being directly coupled to closure of loops over the active site
      and formation of the reactive complex. The mutation destabilizes this initial
      event.

PMID- 29589923
TI  - Surprisingly Flexible Oxonium/Borohydride Ion Pair Configurations.
AB  - We investigate the geometry of oxonium/borohydride ion pairs [ether-H(+)
      ether][LA-H(-)] with dioxane, THF, and Et2O as ethers and B(C6F5)3 as the Lewis
      acid (LA). The question is about possible location of the disolvated proton,
      [ether-H(+)-ether], with respect to the hydride of the structurally complex [LA
      H(-)] anion. Using Born-Oppenheimer molecular dynamics and a comparison of the
      potential and free energies of the optimized configurations, we show that herein
      considered ion pairs are much more flexible geometrically than previously
      thought. Conformers with different locations of cations with respect to anions
      are governed by a flat energy-landscape. We found a novel configuration in which
      oxonium is below [LA-H(-)], with respect to the direction of borane -> hydride
      vector, and the proton-hydride distance is ca. 6 A. With calculations of the
      vibrational spectra of [ether-H(+)-ether][(C6F5)3B-H(-)] for dioxane, THF, and
      Et2O as ethers, we investigate the manifestation of SSLB-type (short, strong, low
      barrier) hydrogen bonding in the OHO motif of an oxonium cation.

PMID- 29589924
TI  - A Cannibalistic Approach to Grand Canonical Crystal Growth.
AB  - Canonical molecular dynamics simulations of crystal growth from solution suffer
      from severe finite-size effects. As the crystal grows, the solute molecules are
      drawn from the solution to the crystal, leading to a continuous drop in the
      solution concentration. This is in contrast to experiments in which the crystal
      grows at an approximately constant supersaturation of a bulk solution. Recently,
      Perego et al. [ J. Chem. Phys. 2015, 142, 144113] showed that in a periodic setup
      in which the crystal is represented as a slab, the concentration in the vicinity
      of the two surfaces can be kept constant while the molecules are drawn from a
      part of the solution that acts as a molecular reservoir. This method is quite
      effective in studying crystallization under controlled supersaturation
      conditions. However, once the reservoir is depleted, the constant supersaturation
      conditions cannot be maintained. We propose a variant of this method to tackle
      this depletion problem by simultaneously dissolving one side of the crystal while
      letting the other side grow. A continuous supply of particles to the solution due
      to the crystal dissolution maintains a steady solution concentration and avoids
      reservoir depletion. In this way, a constant supersaturation condition can be
      maintained for as long as necessary. We have applied this method to study the
      growth and dissolution of urea crystal from water solution under constant
      supersaturation and undersaturation conditions, respectively. The computed growth
      and dissolution rates are in good agreement with those obtained in previous
      studies.

PMID- 29589925
TI  - Systems Analysis of Physical Absorption of CO2 in Ionic Liquids for Pre
      Combustion Carbon Capture.
AB  - This study develops an integrated technical and economic modeling framework to
      investigate the feasibility of ionic liquids (ILs) for precombustion carbon
      capture. The IL 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide is
      modeled as a potential physical solvent for CO2 capture at integrated
      gasification combined cycle (IGCC) power plants. The analysis reveals that the
      energy penalty of the IL-based capture system comes mainly from the process and
      product streams compression and solvent pumping, while the major capital cost
      components are the compressors and absorbers. On the basis of the plant-level
      analysis, the cost of CO2 avoided by the IL-based capture and storage system is
      estimated to be $63 per tonne of CO2. Technical and economic comparisons between
      IL- and Selexol-based capture systems at the plant level show that an IL-based
      system could be a feasible option for CO2 capture. Improving the CO2 solubility
      of ILs can simplify the capture process configuration and lower the process
      energy and cost penalties to further enhance the viability of this technology.

PMID- 29589927
TI  - Development of the Fragment Molecular Orbital Method for Calculating Nonlocal
      Excitations in Large Molecular Systems.
AB  - We developed the fragment-based method for calculating nonlocal excitations in
      large molecular systems. This method is based on the multilayer fragment
      molecular orbital method and the configuration interaction single (CIS) wave
      function using localized molecular orbitals. The excited-state wave function for
      the whole system is described as a superposition of configuration state functions
      (CSFs) for intrafragment excitations and for interfragment charge-transfer
      excitations. The formulation and calculations of singlet excited-state
      Hamiltonian matrix elements in the fragment CSFs are presented in detail. The
      efficient approximation schemes for calculating the matrix elements are also
      presented. The computational efficiency and the accuracy were evaluated using the
      molecular dimers and molecular aggregates. We confirmed that absolute errors of
      50 meV (relative to the conventional calculations) are achievable for the
      molecular systems in their equilibrium geometries. The perturbative electron
      correlation correction to the CIS excitation energies is also demonstrated. The
      present theory can compute a large number of excited states in large molecular
      systems; in addition, it allows for the systematic derivation of a model exciton
      Hamiltonian. These features are useful for studying excited-state dynamics in
      condensed molecular systems based on the ab initio electronic structure theory.

PMID- 29589928
TI  - Tight-Binding Approximation-Enhanced Global Optimization.
AB  - Solving and predicting atomic structures from first-principles methodologies is
      limited by the computational cost of exploring the search space, even when
      relatively inexpensive density functionals are used. Here, we present an
      efficient approach where the search is performed using density functional tight
      binding, with an automatic adaptive parametrization scheme for the repulsive pair
      potentials. We successfully apply the method to the genetic algorithm
      optimization of bulk carbon, titanium dioxide, palladium oxide, and calcium
      hydroxide, and we assess the stability of the unknown crystal structure of
      palladium hydroxide.

PMID- 29589926
TI  - Designing Well-Structured Cyclic Pentapeptides Based on Sequence-Structure
      Relationships.
AB  - Cyclic peptides are a promising class of molecules for unique applications.
      Unfortunately, cyclic peptide design is severely limited by the difficulty in
      predicting the conformations they will adopt in solution. In this work, we use
      explicit-solvent molecular dynamics simulations to design well-structured cyclic
      peptides by studying their sequence-structure relationships. Critical to our
      approach is an enhanced sampling method that exploits the essential transitional
      motions of cyclic peptides to efficiently sample their conformational space. We
      simulated a range of cyclic pentapeptides from all-glycine to a library of cyclo
      (X1X2AAA) peptides to map their conformational space and determine cooperative
      effects of neighboring residues. By combining the results from all cyclo
      (X1X2AAA) peptides, we developed a scoring function to predict the structural
      preferences for X1-X2 residues within cyclic pentapeptides. Using this scoring
      function, we designed a cyclic pentapeptide, cyclo-(GNSRV), predicted to be well
      structured in aqueous solution. Subsequent circular dichroism and NMR
      spectroscopy revealed that this cyclic pentapeptide is indeed well structured in
      water, with a nuclear Overhauser effect and J-coupling values consistent with the
      predicted structure.

PMID- 29589929
TI  - Investigating the Dynamics of Destabilized Nucleosomes Using Methyl-TROSY NMR.
AB  - The nucleosome core particle (NCP), comprised of histone proteins wrapped with
      ~146 base pairs of DNA, provides both protection and controlled access to DNA so
      as to regulate vital cellular processes. High-resolution structures of
      nucleosomes and nucleosome complexes have afforded a clear understanding of the
      structural role of NCPs, but a detailed description of the dynamical properties
      that facilitate DNA-templated processes is only beginning to emerge. Using methyl
      TROSY NMR approaches we evaluate the effect of point mutations designed to
      perturb key histone interfaces that become destabilized during nucleosome
      remodeling in an effort to probe NCP plasticity. Notably the NCP retains its
      overall structural integrity, yet relaxation experiments of mutant nucleosomes
      reveal significant dynamics within a central histone interface associated with
      alternative NCP conformations populated to as much as 15% under low salt
      conditions. This work highlights the inherent plasticity of NCPs and establishes
      methyl-TROSY NMR as a valuable compliment to current single molecule methods in
      quantifying NCP dynamic properties.

PMID- 29589930
TI  - Preparation and Characterization of a Small Library of Thermally-Labile End-Caps
      for Variable-Temperature Triggering of Self-Immolative Polymers.
AB  - The reaction between furans and maleimides has increasingly become a method of
      interest as its reversibility makes it a useful tool for applications ranging
      from self-healing materials, to self-immolative polymers, to hydrogels for cell
      culture and for the preparation of bone repair. However, most of these
      applications have relied on simple monosubstituted furans and simple maleimides
      and have not extensively evaluated the potential thermal variability inherent in
      the process that is achievable through simple substrate modification. A small
      library of cycloadducts suitable for the above applications was prepared, and the
      temperature dependence of the retro-Diels-Alder processes was determined through
      in situ 1H NMR analyses complemented by computational calculations. The practical
      range of the reported systems ranges from 40 to >110  degrees C. The
      cycloreversion reactions are more complex than would be expected based on simple
      trends expected based on frontier molecular orbital analyses of the materials.

PMID- 29589931
TI  - Synthesis and Complete Structure Determination of a Sperm-Activating and 
      Attracting Factor Isolated from the Ascidian Ascidia sydneiensis.
AB  - For the complete structure elucidation of an endogenous sperm-activating and 
      attracting factor isolated from eggs of the ascidian Ascidia sydneiensis ( Assydn
      SAAF), its two possible diastereomers with respect to C-25 were synthesized.
      Starting from ergosterol, the characteristic steroid backbone was constructed by
      using an intramolecular pinacol coupling reaction and stereoselective reduction
      of a hydroxy ketone as key steps, and the side chain was introduced by Julia
      Kocienski olefination. Comparison of the NMR data of the two diastereomers with
      those of the natural product led to the elucidation of the absolute configuration
      as 25 S; thus the complete structure was determined and the first synthesis of
      Assydn-SAAF was achieved.

PMID- 29589932
TI  - Synthesis and Structure-Activity Relationships of the Novel Antimalarials 5
      Pyridinyl-4(1 H)-Pyridones.
AB  - Malaria is still one of the most prevalent parasitic infections in the world,
      with half of the world's population at risk for malaria. The effectiveness of
      current antimalarial therapies, even that of the most recent class of
      antimalarial drugs (artemisinin-combination therapies, ACTs), is under continuous
      threat by the spread of resistant Plasmodium strains. As a consequence, there is
      still an urgent requirement for new antimalarial drugs. We previously reported
      the identification of 4(1 H)-pyridones as a novel series with potent antimalarial
      activities. The low solubility was identified as an issue to address. In this
      paper, we describe the synthesis and biological evaluation of 4(1 H)-pyridones
      with potent antimalarial activities in vitro and in vivo and improved
      pharmacokinetic profiles. Their main structural novelties are the presence of
      polar moieties, such as hydroxyl groups, and the replacement of the lipophilic
      phenyl rings with pyridines on their lipophilic side chains.

PMID- 29589933
TI  - Structural Characterization of Biocompatible Reverse Micelles Using Small-Angle X
      ray Scattering, 31P Nuclear Magnetic Resonance, and Fluorescence Spectroscopy.
AB  - The most critical problem regarding the use of reverse micelles (RMs) in several
      fields is the toxicity of their partial components. In this sense, many efforts
      have been made to characterize nontoxic RM formulations on the basis of
      biological amphiphiles and/or different oils. In this contribution, the
      microstructure of biocompatible mixed RMs formulated by sodium 1,4-bis-2
      ethylhexylsulfosuccinate (AOT) and tri- n-octylphosphine oxide (TOPO) surfactants
      dispersed in the friendly solvent methyl laurate was studied by using SAXS and
      31P NMR and by following the solvatochromic behavior of the molecular probe 4
      aminophthalimide (4-AP). The results indicated the presence of RM aggregates upon
      TOPO incorporation with a droplet size reduction and an increase in the
      interfacial fluidity in comparison with pure AOT RMs. When confined inside the
      mixed systems, 4-AP showed a red-edge excitation shift and confirmed the
      increment of interfacial fluidity upon TOPO addition. Also, the partition between
      the external nonpolar solvent and the RM interface and an increase in both the
      local micropolarity and the capability to form a hydrogen bond interaction
      between 4-AP and a mixed interface were observed. The findings have been
      explained in terms of the nonionic surfactant structure and its complexing nature
      expressed at the interfacial level. Notably, we show how two different
      approaches, i.e., SAXS and the solvatochromism of the probe 4-AP, can be used in
      a complementary way to enhance our understanding of the interfacial fluidity of
      RMs, a parameter that is difficult to measure directly.

PMID- 29589934
TI  - Correction to Discovery of the Hemifumarate and (alpha-l-Alanyloxy)methyl Ether
      as Prodrugs of an Antirheumatic Oxindole: Prodrugs for the Enolic OH Group.

PMID- 29589935
TI  - Lipophilic Efficiency as an Important Metric in Drug Design.
AB  - Lipophilic efficiency (LipE) is an important metric that has been increasingly
      applied in drug discovery medicinal chemistry lead optimization programs. In this
      Perspective, using literature drug discovery examples, we discuss the concept of
      rigorously applying LipE to guide medicinal chemistry lead optimization toward
      drug candidates with potential for superior in vivo efficacy and safety,
      especially when guided by physiochemical property-based optimization (PPBO). Also
      highlighted are examples of small structural modifications such as addition of
      single atoms, small functional groups, and cyclization that produce large
      increases in LipE. Understanding the factors that may contribute to LipE changes
      through analysis of ligand-protein crystal structures and using structure-based
      drug design (SBDD) to increase LipE by design is also discussed. Herein we
      advocate for use of LipE analysis coupled with PPBO and SBDD as an efficient
      mechanism for drug design.

PMID- 29589936
TI  - Short Synthesis of the Monoterpene Indole Alkaloid (+/-)-Arbornamine.
AB  - The first total synthesis of the monoterpene indole alkaloid (+/-)-arbornamine
      (1) has been completed, which proceeds in only 6 steps and 31% overall yield from
      three readily available, known compounds. The synthesis features a cascade
      involving a Pictet-Spengler cyclization/intramolecular ammonolysis to create the
      tetracyclic core of arbornamine (1) in a single chemical operation. The
      subsequent elaboration of 5 into 1 was effected by a key reductive Heck reaction
      and global reduction.

PMID- 29589938
TI  - Rapid Trace Detection and Isomer Quantitation of Pesticide Residues via Matrix
      Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance
      Mass Spectrometry.
AB  - Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron
      resonance mass spectrometry (MALDI-FTICR-MS) has been applied for rapid,
      sensitive, undisputed, and quantitative detection of pesticide residues on fresh
      leaves with little sample pretreatment. Various pesticides (insecticides,
      bactericides, herbicides, and acaricides) are detected directly in the complex
      matrix with excellent limits of detection down to 4 MUg/L. FTICR-MS could
      unambiguously identify pesticides with tiny mass differences (~0.017 75 Da),
      thereby avoiding false-positive results. Remarkably, pesticide isomers can be
      totally discriminated by use of diagnostic fragments, and quantitative analysis
      of pesticide isomers is demonstrated. The present results expand the horizons of
      the MALDI-FTICR-MS platform in the reliable determination of pesticides, with
      integrated advantages of ultrahigh mass resolution and accuracy. This method
      provides growing evidence for the resultant detrimental effects of pesticides,
      expediting the identification and evaluation of innovative pesticides.

PMID- 29589937
TI  - Rheology of Membrane-Attached Minimal Actin Cortices.
AB  - The actin cortex is a thin cross-linked network attached to the plasma membrane,
      which is responsible for the cell's shape during migration, division, and growth.
      In a reductionist approach, we created a minimal actin cortex (MAC) attached to a
      lipid membrane to correlate the filamentous actin architecture with its
      viscoelastic properties. The system is composed of a supported 1-palmitoyl-2
      oleoyl- sn-glycero-3-phosphocholine bilayer doped with the receptor lipid
      phosphatidylinositol(4,5)-bisphosphate (PtdIns(4,5)P2) to which a constitutively
      active mutant of ezrin, which is a direct membrane-cytoskeleton linker, is bound.
      The formation of the MAC on the supported lipid bilayer is analyzed as a function
      of increasing PtdIns(4,5)P2/ezrin pinning points, revealing an increase in the
      intersections between actin filaments, that is, the node density of the MAC. Bead
      tracking microrheology on the membrane-attached actin network provides
      information about its viscoelastic properties. The results show that ezrin serves
      as a dynamic cross-linker for the actin cortex attached to the lipid bilayer and
      that the stiffness of the network is influenced by the pinning point density,
      relating the plateau storage modulus G0 to the node density of the MAC.

PMID- 29589939
TI  - Compound Synthesis or Growth and Development of Roots/Stomata Regulate Plant
      Drought Tolerance or Water Use Efficiency/Water Uptake Efficiency.
AB  - Water is crucial to plant growth and development because it serves as a medium
      for all cellular functions. Thus, the improvement of plant drought tolerance or
      water use efficiency/water uptake efficiency is important in modern agriculture.
      In this review, we mainly focus on new genetic factors for ameliorating drought
      tolerance or water use efficiency/water uptake efficiency of plants and explore
      the involvement of these genetic factors in the regulation of improving plant
      drought tolerance or water use efficiency/water uptake efficiency, which is a
      result of altered stomata density and improving root systems (primary root
      length, hair root growth, and lateral root number) and enhanced production of
      osmotic protectants, which is caused by transcription factors, proteinases, and
      phosphatases and protein kinases. These results will help guide the synthesis of
      a model for predicting how the signals of genetic and environmental stress are
      integrated at a few genetic determinants to control the establishment of either
      water use efficiency or water uptake efficiency. Collectively, these insights
      into the molecular mechanism underpinning the control of plant drought tolerance
      or water use efficiency/water uptake efficiency may aid future breeding or design
      strategies to increase crop yield.

PMID- 29589940
TI  - Simultaneous Improvement of Antimicrobial, Antifouling, and Transport Properties
      of Forward Osmosis Membranes with Immobilized Highly-Compatible Polyrhodanine
      Nanoparticles.
AB  - This work shows that incorporating highly compatible polyrhodanine nanoparticles
      (PRh-NPs) into a polyamide (PA) active layer allows for fabricating forward
      osmosis (FO) thin-film composite (TFC)-PRh membranes that have simultaneously
      improved antimicrobial, antifouling, and transport properties. To the best of our
      knowledge, this is the first reported study of its kind to this date. The
      presence of the PRh-NPs on the surface of the TFC-PRh membranes active layers is
      evaluated using FT-IR spectroscopy, SEM, and XPS. The microscopic interactions
      and their impact on the compatibility of the PRh-NPs with the PA chains were
      studied using molecular dynamics simulations. When tested in forward osmosis, the
      TFC-PRh-0.01 membrane (with 0.01 wt % PRh) shows significantly improved
      permeability and selectivity because of the small size and the high compatibility
      of the PRh-NPs with PA chains. For example, the TFC-PRh-0.01 membrane exhibits a
      FO water flux of 41 l/(m2.h), higher than a water flux of 34 l/(m2.h) for the
      pristine TFC membrane, when 1.5 molar NaCl was used as draw solution in the
      active-layer feed-solution mode. Moreover, the reverse solute flux of the TFC-PRh
      0.01 membrane decreases to about 115 mmol/(m2.h) representing a 52% improvement
      in the reverse solute flux of this membrane in comparison to the pristine TFC
      membrane. The surfaces of the TFC-PRh membranes were found to be smoother and
      more hydrophilic than those of the pristine TFC membrane, providing improved
      antifouling properties confirmed by a flux decline of about 38% for the TFC-PRh
      0.01 membranes against a flux decline of about 50% for the pristine TFC membrane
      when evaluated with a sodium alginate solution. The antimicrobial traits of the
      TFC-PRh-0.01 membrane evaluated using colony-forming units and fluorescence
      imaging indicate that the PRh-NPs hinder cell deposition on the TFC-PRh-0.01
      membrane surface effectively, limiting biofilm formation.

PMID- 29589941
TI  - Enantioselective Total Synthesis of the Fungal Metabolite Blennolide D and the
      Enantiomers of Blennolide E and F.
AB  - An enantioselective total synthesis of blennolide D and the enantiomers of
      blennolide E and F is described using an enantioselective Wacker-type oxidation
      followed by the formation of the lactone moiety. For the introduction of the
      hydroxyl group in the gamma-lactone, a TEMPO-mediated alpha-oxygenation was used
      which was followed by a benzylic oxidation and deprotection to give the desired
      compounds. In addition, an unknown diastereomer was synthesized.

PMID- 29589942
TI  - Pyridinium Analogues of Green Fluorescent Protein Chromophore: Fluorogenic Dyes
      with Large Solvent-Dependent Stokes Shift.
AB  - Novel fluorogenic dyes based on the GFP chromophore are developed. The compounds
      contain a pyridinium ring instead of phenolate and feature large Stokes shifts
      and solvent-dependent variations in the fluorescence quantum yield. Electronic
      structure calculations explain the trends in solvatochromic behavior in terms of
      the increase of the dipole moment upon excited-state relaxation in polar solvents
      associated with the changes in bonding pattern in the excited state. A unique
      combination of such optical characteristics and lipophilic properties enables
      using one of the new dyes for imaging the membrane structure of endoplasmic
      reticulum. An extremely high photostability (due to a dynamic exchange between
      the free and absorbed states) and selectivity make this compound a promising
      label for this type of cellular organelles.

PMID- 29589943
TI  - Facile Quantum Yield Determination via NMR Actinometry.
AB  - A simplified approach to quantum yield ([Formula: see text]) measurement using in
      situ LED NMR spectroscopy has been developed. The utility and performance of NMR
      actinometry has been demonstrated for the well-known chemical actinometers
      potassium ferrioxalate and o-nitrobenzaldehyde. A novel NMR-friendly actinometer,
      2,4-dinitrobenzaldehyde, has been introduced for both 365 and 440 nm wavelengths.
      The method has been utilized successfully to measure the quantum yield of several
      recently published photochemical reactions.

PMID- 29589944
TI  - Insights into Pipecolic Acid Biosynthesis in Huperzia serrata.
AB  - For the biosynthesis of Pip in Huperzia serrata, the mechanistic studies were
      evaluated. Through a series of biochemical analyses, Pip is biosynthesized
      through a two-step cascade reaction. Three intermediates possibly exist
      simultaneously as an equilibrium matter in the first-step reaction catalyzed by
      HsAld1, while HsSard4 performs as a ketimine reductase and chemoselectively and
      stereoselectively takes 1,2-dehydropipecolic acid as the preferred substrate in
      vitro.

PMID- 29589945
TI  - Slippery Liquid-Infused Porous Surfaces (SLIPS) Using Layer-by-Layer
      Polyelectrolyte Assembly in Organic Solvent.
AB  - Slippery liquid-infused porous surfaces (SLIPS) have potential impact on a wide
      range of industries, including healthcare, food packaging, and automobile. A
      tremendouseffort has been focused on developing novel fabrication methods for
      making SLIPS. However, current fabrication methods usually involve harsh
      conditions and complicated postfabrication modifications or are limited to
      specific substrates. Presented here is a novel method for the fast and facile
      fabrication of SLIPS. Layer-by-layer (LBL) assembly of branched polyethylenimine
      and Nafion, a perfluorinated polyelectrolyte, is performed with methanol as the
      solvent. Hierarchically rough and superhydrophobic surface is obtained directly
      without further modification on various substrates. The surface properties are
      shown to highly depend on the LBL assembly parameters, including deposition
      cycles, dipping time, rinsing time, and drying time between baths. The
      polyelectrolyte multilayers obtained with this method are infused with Krytox 100
      to form SLIPS surfaces, which show excellent omniphobic, antifouling, self
      cleaning, flexible, and optical properties. The result of this study not only
      simplifies the fabrication of SLIPS surfaces, but also provides great insight for
      making LBL films with specific morphologies.

PMID- 29589946
TI  - Synthesis of Benzyl Amines via Copper-Catalyzed Enantioselective Aza-Friedel
      Crafts Addition of Phenols to N-Sulfonyl Aldimines.
AB  - A new copper-catalyzed enantioselective aza-Freidel-Crafts reaction between
      phenols and N-sulfonyl aldimines that provides chiral secondary benzylamines in
      good to excellent yields and excellent enantioselectivities (up to 99% ee) is
      disclosed. In particular, excellent scope with alkylimines was observed for the
      first time. The synthetic utility of the products was demonstrated in the first
      enantioselective synthesis of a dual orexin receptor antagonist, a compound that
      contains an amine-bearing stereocenter adjacent to a bis- ortho-functionalized
      arene.

PMID- 29589947
TI  - Cu-Mediated Sulfonyl Radical-Enabled 5- exo-trig Cyclization of Alkenyl
      Aldehydes: Access to Sulfonylmethyl 1 H-Indenes.
AB  - An efficient method for the construction of sulfonylmethyl 1 H-indenes via Cu(I)
      mediated sulfonyl radical-enabled 5- exo-trig cyclization of alkenyl aldehydes
      has been developed for the first time. Mechanistic studies indicated that a
      radical addition-cyclization-elimination (RACE) process might be involved. The
      reaction features a relatively broad substrate scope, good annulation efficiency,
      and varying functional group tolerance.

PMID- 29589948
TI  - (3 + 3) Cycloaddition of Oxyallyl Cations with Nitrones: Diastereoselective
      Access to 1,2-Oxazinanes.
AB  - Oxyallyl cations are prepared in situ from readily available alpha-tosyloxy
      ketones and act as transient electrophilic partners in (3 + 3) cycloaddition with
      nitrones. Under mild conditions, this method provides a chemoselective and
      diastereoselective route to polysubstituted 1,2-oxazinanes. A stepwise process is
      proposed to rationalize the diastereoselectivity of this transformation.

PMID- 29589949
TI  - Strain-Driven Stacking Faults in CdSe/CdS Core/Shell Nanorods.
AB  - Colloidal semiconductor nanocrystals are commonly grown with a shell of a second
      semiconductor material to obtain desired physical properties, such as increased
      photoluminescence quantum yield. However, the growth of a lattice-mismatched
      shell results in strain within the nanocrystal, and this strain has the potential
      to produce crystalline defects. Here, we study CdSe/CdS core/shell nanorods as a
      model system to investigate the influence of core size and shape on the formation
      of stacking faults in the nanocrystal. Using a combination of high-angle annular
      dark-field scanning transmission electron microscopy and pair-distribution
      function analysis of synchrotron X-ray scattering, we show that growth of the CdS
      shell on smaller, spherical CdSe cores results in relatively small strain and few
      stacking faults. By contrast, growth of the shell on larger, prolate spheroidal
      cores leads to significant strain in the CdS lattice, resulting in a high density
      of stacking faults.

PMID- 29589950
TI  - Dual-Frequency Comb Transient Absorption: Broad Dynamic Range Measurement of
      Femtosecond to Nanosecond Relaxation Processes.
AB  - We experimentally demonstrate a dual-frequency comb-based transient absorption
      (DFC-TA) technique, which has a 12 fs time resolution and an ultrafast scan rate.
      Here, the fast scan rate is achieved by employing asynchronous optical sampling
      (ASOPS), which utilizes two independent mode-locked lasers with a slightly
      detuned repetition rates. The ASOPS approach is advantageous because
      photodegradation damage of optical sample during TA measurements can be minimized
      by a gated sampling. We show that the vibrational and electronic population
      relaxations of near-IR dye molecules in solution that occur in the time range
      from femtoseconds to nanoseconds can be resolved even with a single time scan
      measurement. The phase coherent nature of our dual-frequency comb lasers is shown
      to be the key for successful coherent averaging with femtosecond time resolution
      preserved over many data acquisitions. We anticipate that the present DFC-TA
      method without using any pump-probe time delay devices could be of use in
      developing ultrafast TA-based microscopy and time-resolved coherent
      multidimensional spectroscopy.

PMID- 29589951
TI  - Optical Imaging and Spectroscopic Characterization of Self-Assembled
      Environmental Adsorbates on Graphene.
AB  - Topographic studies using scanning probes have found that graphene surfaces are
      often covered by micron-scale domains of periodic stripes with a 4 nm pitch.
      These stripes have been variously interpreted as structural ripples or as self
      assembled adsorbates. We show that the stripe domains are optically anisotropic
      by imaging them using a polarization-contrast technique. Optical spectra between
      1.1 and 2.8 eV reveal that the anisotropy in the in-plane dielectric function is
      predominantly real, reaching 0.6 for an assumed layer thickness of 0.3 nm. The
      spectra are incompatible with a rippled graphene sheet but would be
      quantitatively explained by the self-assembly of chainlike organic molecules into
      nanoscale stripes.

PMID- 29589953
TI  - Ten-Year Results of Medial Open-Wedge High Tibial Osteotomy and Chondral
      Resurfacing in Severe Medial Osteoarthritis and Varus Malalignment.
AB  - BACKGROUND: High tibial osteotomy (HTO) is a widely used treatment option for
      medial osteoarthritis and varus malalignment, especially in young patients with
      early osteoarthritis. Limited outcome data are available for this procedure in
      severe osteoarthritis, and no long-term data are available using newer implants.
      PURPOSE: To determine survivorship and functional results of medial open-wedge
      HTO combined with a chondral resurfacing (CR) procedure (abrasion plus
      microfracture) in severe medial osteoarthritis (Kellgren-Lawrence grade 3 and 4)
      and varus malalignment. Furthermore, factors that potentially influence the
      outcome were analyzed. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      From September 2005 to December 2008, all cases of HTO (fixation with an angular
      stable internal fixator) combined with CR were prospectively surveyed with regard
      to survival (Kaplan-Meier-method, not requiring arthroplasty) and functional
      outcome (subjective International Knee Documentation Committee [IKDC] score).
      Cartilage regeneration at the time of hardware removal, tibial bone varus angle
      (TBVA), pre- and postoperative mechanical medial proximal tibial angle (MPTA),
      and postoperative alignment were analyzed with regard to the result. RESULTS:
      Seventy-nine knees were included (73 patients; mean age 50.9 +/- 7.6 years). The
      follow-up rate was 90% at 10.0 +/- 1.2 years (range, 8.3-12.1 years). Pre- and
      postoperative mechanical tibiofemoral axis were 9.6 degrees  +/- 3.0 degrees  of
      varus and 0.6 degrees  +/- 2.7 degrees  of valgus, respectively. Survival rate
      was 81.7% (95% CI, 72.5%-90.9%) at 10 years. Subjective IKDC score significantly
      improved from 44 +/- 11 preoperatively to 70 +/- 13 at one, 66 +/- 15 at three,
      66 +/- 15 at five, and 65 +/- 17 at ten years ( P < .001 at any point of follow
      up). Poor cartilage regeneration and low preoperative IKDC score (<40) were
      associated with decreased survival. High preoperative TBVA was associated with
      better and an overcorrected MPTA (>95 degrees ) with inferior functional outcome
      at final follow-up, respectively. CONCLUSION: Even in cases of severe medial
      osteoarthritis and varus malalignment, HTO in combination with a CR procedure is
      a good to excellent treatment option. The role of the CR procedure remains
      unclear. Although good results are obtained with overcorrected MPTA, long-term
      functional outcome is inferior.

PMID- 29589952
TI  - Direct Mapping of Phase Separation across the Metal-Insulator Transition of
      NdNiO3.
AB  - Perovskite rare-earth nickelates RNiO3 are prototype correlated oxides displaying
      a metal-insulator transition (MIT) at a temperature tunable by the ionic radius
      of the rare-earth R. Although its precise origin remains a debated topic, the MIT
      can be exploited in various types of applications, notably for resistive
      switching and neuromorphic computation. So far, the MIT has been mostly studied
      by macroscopic techniques, and insights into its nanoscale mechanisms were only
      provided recently by X-ray photoemission electron microscopy through absorption
      line shifts, used as an indirect proxy to the resistive state. Here, we directly
      image the local resistance of NdNiO3 thin films across their first-order MIT
      using conductive-atomic force microscopy. Our resistance maps reveal the
      nucleation of ~100-300 nm metallic domains in the insulating state that grow and
      percolate as temperature increases. We discuss the resistance contrast mechanism,
      analyze the microscopy and transport data within a percolation model, and propose
      experiments to harness this mesoscopic electronic texture in devices.

PMID- 29589954
TI  - Validation of an MRI Protocol for Routine Quantitative Assessment of Tunnel
      Position in Anterior Cruciate Ligament Reconstruction.
AB  - BACKGROUND: No standardized methodology and objective criteria currently exist to
      accurately and objectively assess tunnel placement and consequent graft
      orientation in anterior cruciate ligament (ACL) reconstruction (ACLR) through a
      single imaging modality. Advances in magnetic resonance imaging (MRI) technology
      have enabled the use of volumetric high spatial and contrast resolution proton
      density-weighted sequencing, which allows precise delineation of graft
      orientation, tunnel position, and quantitative assessment of tunnel position
      relationship to adjacent reproducible anatomic landmarks. PURPOSE: To establish
      an MRI protocol that would provide an accurate alternative to 3-dimensional
      computed tomography (3D-CT) for standardized assessment of bone tunnel placement
      in ACLR, as a component of assessing ACLR outcomes and to assist in presurgical
      planning for revision ACLR. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 2. METHODS: Twenty-four participants diagnosed with a failed ACLR
      underwent MRI and 3D-CT per the imaging protocols of the Sydney Orthopaedic
      Research Institute, in which the acquired data were converted to 3D models. The
      bone tunnels of the previous ACLR were then intraoperatively digitized at the
      tunnel aperture and along the length of the tunnel (barrel) and used as the
      reference standard to evaluate the accuracy of high-resolution MRI and 3D-CT.
      Differences in geometry between the image-based model and the reference point
      cloud were calculated through point-to-point comparison. RESULTS: At the tunnel
      apertures, no significant differences were detected between the MRI and 3D-CT
      models versus the reference models for the femur ( P = .9472) and tibia ( P =
      .5779). Mean +/- SD tunnel barrel deviations between MRI and 3D-CT were 0.48 +/-
      0.28 mm (femur) and 0.46 +/- 0.27 mm (tibia). No significant differences were
      detected between the MRI and 3D-CT models versus the reference models for the
      femoral ( P = .5730) and tibial ( P = .3002) tunnel barrels. CONCLUSION: This
      study demonstrated that, in addition to being the optimum modality for assessment
      of soft tissue injury of the knee, a high-resolution 3D turbo spin echo proton
      density sequence can provide an accurate assessment of tunnel placement, without
      the use of ionizing radiation. Therefore, this protocol provides the foundation
      for an objective standardized platform to quantitatively evaluate the location of
      ACL bone tunnels and graft orientation for routine postoperative assessment,
      presurgical planning, and evaluation of clinical outcomes.

PMID- 29589955
TI  - Open Latarjet Procedures Produce Better Outcomes in Competitive Athletes Compared
      With Recreational Athletes: A Clinical Comparative Study of 106 Athletes Aged
      Under 30 Years.
AB  - BACKGROUND: In cases of shoulder stabilization for anterior instability, the main
      goals of the surgery are a rapid and efficient return to sports and excellent
      long-term outcomes without recurrence of dislocation, particularly in young and
      competitive athletes. PURPOSE: To determine whether outcomes of open Latarjet
      procedure (OLPs) depend on the level of sports practiced by patients and to
      report clinical scores and complication rates for OLP at a minimum follow-up of 2
      years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective
      comparative study was conducted for all patients who underwent OLP by the senior
      author (J.B.) between July 2007 and December 2012. The indication for OLP at the
      authors' institution was a minimum of 2 episodes of dislocation and/or
      subluxation, a positive apprehension test result in the cocking position, an
      Instability Severity Index Score more than 2, and evidence of anterior
      instability lesions on computed tomography arthrograms. The 106 included patients
      (110 shoulders) with a mean follow-up of 46 months were compared in 2 groups
      depending on sport activities: 57 (54%) competitive athletes and 49 (46%)
      recreational athletes. The principal outcome measure was evidence of recurrent
      instability. The secondary outcome measures were clinical scores related to
      anterior instability and related to sport practice: Rowe score, Oxford Shoulder
      Instability Score (OSIS), Western Ontario Shoulder Instability Index, and level
      of satisfaction. RESULTS: Of the 106 patients, 3 reported recurrence of shoulder
      dislocation: 2 competitive athletes (3.5%; 95% CI, 0.9%-11.2%) and 1 recreational
      athlete (2%; 95% CI, 0.4%-10.7%) ( P = .684). The persistent apprehension test
      result was positive in 7 competitive athletes (11.5%) and in 5 recreational
      athletes (10%) ( P = .566). The Rowe scores improved from 56.3 +/- 13.2 (range,
      30-80) preoperatively to 84.2 +/- 16.4 (range, 30-100) postoperatively in
      competitive athletes and from 55.0 +/- 11.0 (range, 35-80) to 69.5 +/- 22.0
      (range, 15-100) in recreational athletes ( P < .001). The net improvement in Rowe
      scores was significantly greater in competitive athletes (27.9 +/- 21.7) compared
      with recreational athletes (14.5 +/- 24.4) ( P = .006). The scores unrelated to
      sport activity (Oxford Shoulder Instability Score and Simple Shoulder Test) were
      similar for the 2 groups. All 57 (100%) competitive athletes and 34 (69.4%)
      recreational athletes resumed their previous sports practice, at the same level
      or higher than before their injury (respectively, 78.9% and 42.9%; P = .004).
      CONCLUSION: The OLP could be considered for primary shoulder stabilization,
      particularly in competitive athletes, who have high functional demands and great
      risks of redislocation.

PMID- 29589957
TI  - Understanding the Hurdles in Lung Cancer Immunotherapy in the Context of Chronic
      Obstructive Pulmonary Disease.

PMID- 29589956
TI  - Associations of Early Treatments for Low-Back Pain with Military Readiness
      Outcomes.
AB  - BACKGROUND: Chronic low-back pain (LBP) is a frequent cause of work absence and
      disability, and is frequently associated with long-term use of opioids.
      OBJECTIVE: To describe military readiness-related outcomes at follow-up in
      soldiers with LBP grouped by the type of early treatment received for their LBP.
      Treatment groups were based on receipt of opioid or tramadol prescription and
      receipt of nonpharmacologic treatment modalities (NPT). Design, Subjects,
      Measures: A retrospective longitudinal analysis of U.S. soldiers with new LBP
      episodes persisting more than 90 days between October 2012 and September 2014.
      Early treatment groups were constructed based on utilization of services within
      30 days of the first LBP claim. Outcomes were measured 91-365 days after the
      first LBP claim. Outcomes were constructed to measure five indicators of
      limitations of military readiness: military duty limitations, pain-related
      hospitalization, emergency room visit for LBP, pain score of moderate/severe, and
      prescription for opioid/tramadol. RESULTS: Among soldiers with no opioid receipt
      in the prior 90 days, there were 30,612 new episodes of LBP, which persisted more
      than 90 days. Multivariable logistic regression models found that compared to the
      reference group (no NPT, no opioids/tramadol receipt), soldiers who received
      early NPT-only had lower likelihoods for military duty limitations, pain-related
      hospitalization, and opioid/tramadol prescription at follow-up, while soldiers'
      that started with opioid receipt (at alone or follow-up in conjunction with NPT)
      exhibited higher likelihoods on many of these negative outcomes. CONCLUSION: This
      observational study of soldiers with a new episode of LBP and no opioid receipt
      in the prior 90 days suggests that early receipt of NPT may be associated with
      small, significant gains in ability to function as a soldier and reduced reliance
      on opioid/tramadol medication. While further research is warranted, increased
      access to NPT at the beginning of LBP episodes should be considered.

PMID- 29589958
TI  - Regulation of RNA Polymerase I TranscriptioninDevelopment, Disease, and Aging.
AB  - Ribosome biogenesis is a complex and highly energy-demanding process that
      requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in
      eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor
      transcript (pre-rRNA) that is encoded by multicopy genes located in the
      nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key
      regulation step in ribosome production and is tightly controlled by an intricate
      network of signaling pathways and epigenetic mechanisms. In this article, we give
      an overview of the composition of the basal Pol I machinery and rDNA chromatin.
      We discuss rRNA gene regulation in response to environmental signals and
      developmental cues and focus on perturbations occurring in diseases linked to
      either excessive or limited rRNA levels. Finally, we discuss the emerging view
      that rDNA integrity and activity may be involved in the aging process.

PMID- 29589960
TI  - A longitudinal large-scale objective sleep data analysis revealed a seasonal
      sleep variation in the Japanese population.
AB  - In the contemporary era, when life habits are largely determined by social needs
      and individual preferences, sleep is nevertheless affected by seasonal
      environmental changes. Japan has large seasonal and geographical alterations of
      photoperiod and climate. Japan does not adopt the daylight saving time (DST)
      system, making it a suitable country for the study of seasonal variations in
      natural human sleep. The aim of this study was to analyze the seasonal changes in
      the sleep properties (timing and quality) and identify their relationship with
      environmental changes. Here, we report an analysis of objective sleep data of 691
      161 nights collected from 1856 Japanese participants (age 20-79 years, male 91%,
      female 9%) for 3 years using contactless biomotion sensors. Sleep onset time did
      not show clear seasonal variation, but sleep offset time showed a seasonal change
      with a single latest peak in winter. Seasonal variation was larger during
      weekends than during weekdays. Sleep offset time well correlated with sunrise
      time but was different in spring and autumn even when the sunrise time was same,
      suggesting the role of temperature difference. Sleep quality, estimated by wake
      time after sleep onset and sleep efficiency, showed seasonal changes with the
      lowest trough around mid-summer. In conclusion, despite profound social
      influences, the timing and quality of sleep showed seasonal fluctuation
      indicating that they were influenced by climate factors even in the developed
      country.

PMID- 29589959
TI  - Understanding and Improving the Activity of Flavin-Dependent Halogenases via
      Random and Targeted Mutagenesis.
AB  - Flavin-dependent halogenases (FDHs) catalyze the halogenation of organic
      substrates by coordinating reactions of reduced flavin, molecular oxygen, and
      chloride. Targeted and random mutagenesis of these enzymes have been used to both
      understand and alter their reactivity. These studies have led to insights into
      residues essential for catalysis and FDH variants with improved stability,
      expanded substrate scope, and altered site selectivity. Mutations throughout FDH
      structures have contributed to all of these advances. More recent studies have
      sought to rationalize the impact of these mutations on FDH function and to
      identify new FDHs to deepen our understanding of this enzyme class and to expand
      their utility for biocatalytic applications.

PMID- 29589961
TI  - 3D Printed Organ Models for Surgical Applications.
AB  - Medical errors are a major concern in clinical practice, suggesting the need for
      advanced surgical aids for preoperative planning and rehearsal. Conventionally,
      CT and MRI scans, as well as 3D visualization techniques, have been utilized as
      the primary tools for surgical planning. While effective, it would be useful if
      additional aids could be developed and utilized in particularly complex
      procedures involving unusual anatomical abnormalities that could benefit from
      tangible objects providing spatial sense, anatomical accuracy, and tactile
      feedback. Recent advancements in 3D printing technologies have facilitated the
      creation of patient-specific organ models with the purpose of providing an
      effective solution for preoperative planning, rehearsal, and spatiotemporal
      mapping. Here, we review the state-of-the-art in 3D printed, patient-specific
      organ models with an emphasis on 3D printing material systems, integrated
      functionalities, and their corresponding surgical applications and implications.
      Prior limitations, current progress, and future perspectives in this important
      area are also broadly discussed.

PMID- 29589962
TI  - Clinical Outcome of Resected Remnant Pancreatic Cancer After Resection of the
      Primary Pancreatic Cancer.
AB  - PURPOSE: Pancreatic cancer (PC) has high morbidity and mortality rates, with a
      poor prognosis and frequent recurrence. The postresection survival rate has
      increased but remains low, and remnant PC is becoming more common. This review
      evaluates the current literature pertaining to the clinical outcomes of patients
      with resected remnant PC. MATERIAL AND METHODS: We reviewed publications on
      remnant PC that included repeated and completion pancreatectomy.
      Clinicophysiological data were analyzed, and survival rates were calculated using
      the Kaplan-Meier method. Remnant PC was defined by negative margins at the
      initial operation, a cancer-free interval >1 year, and presence in the remnant
      pancreas. RESULTS: Forty-nine cases of remnant PC selected from the literature
      were examined. Primary and remnant PCs had the same histopathological features in
      29 of 45 patients (64.4%). The median disease-free interval was 44.3 months (12
      143 months). The 1- and 3-year survival rates after repeat pancreatectomy were
      81.5% and 50%, respectively, and the median survival time was 32 months. The age
      of the patient at the time of the first operation independently predicted
      survival in a multivariate analysis. CONCLUSION: In long-term survivors after
      curative resection for PC, resectable remnant PCs should be aggressively removed
      to improve prognosis.

PMID- 29589963
TI  - Serotyping and Genotyping Characterization of Pathogenic Escherichia coli Strains
      in Kimchi and Determination of Their Kinetic Behavior in Cabbage Kimchi During
      Fermentation.
AB  - This study determined the serotyping and genotyping properties of Escherichia
      coli strains isolated from kimchi and various raw vegetables used for kimchi
      preparation. In addition, the kinetic behavior of E. coli strains in kimchi
      during fermentation was also determined using a predictive microbiological model.
      The study results revealed that E. coli isolated from napa cabbage (3.3%; 1/30)
      was enterohemorrhagic E. coli (O6:H34), and eight typical colonies isolated from
      kimchi (15%; 6/40) were enteropathogenic E. coli (H8, H8, H12, H34, H30, O20:H39,
      H39, and H12). The genetic correlation of the strains did not show close genetic
      correlations. On the other hand, the kinetic behavior of E. coli strains in
      kimchi during fermentation using a predictive Baranyi model (primary model) and a
      polynomial equation (secondary model), followed by validation by calculating root
      mean square error (RMSE), revealed that the pathogenic E. coli cell counts
      increased (with RMSE of 0.280 in growth curve) in the early stage of fermentation
      and decreased (with RMSE of 0.920 in death curve) thereafter depending on
      fermentation temperature. Therefore, this finding indicated that pathogenic E.
      coli isolated from kimchi and related vegetables underwent proliferation at the
      beginning of fermentation, which decreased thereafter. Thus, these results of
      this study suggest intake of sufficiently fermented kimchi to prevent potential
      foodborne illness due to pathogenic E. coli.

PMID- 29589965
TI  - Do pre-clinical multiple sclerosis models allow us to measure neurodegeneration
      and clinical progression?

PMID- 29589964
TI  - Screening and surveillance-principles and practice.
AB  - Health screening can only be applied to populations, not individuals. For it to
      be effective, the initial screening test must be acceptable and reasonably
      accurate, the disease must be treatable with better outcomes when treated early
      and the harm and cost associated with screening must not outweigh its benefits.
      Robust evidence is therefore required before systematic screening is implemented.
      Surveillance implies the testing of people at high risk of disease and is
      therefore distinct from screening in both scale (smaller) and intensity
      (greater). In both cases, however, clear information must be provided to
      potential participants so that they can weigh up the balance of benefit and harm
      before deciding on whether or not to engage in the process.

PMID- 29589966
TI  - Vaccine candidates against leishmania under current research.
AB  - INTRODUCTION: The search for vaccines to prevent human leishmaniasis is an active
      field of investigation aimed to prevent the devastating effects of this family of
      diseases on human health. The design and commercialization of several vaccines
      against canine leishmaniasis is a hopeful advance toward the achievement of a
      human vaccine. Areas covered: This review includes a summary of the most relevant
      immunological aspects accompanying leishmaniasis in natural hosts as well as a
      description of the latest advances in the multiple strategies that are being
      followed to develop leishmanial prophylactic vaccines. We have combined citations
      of the latest specialized reviews with research articles presenting the most
      recent results. Expert commentary: Achieving safe, effective, durable and low
      cost prophylactic vaccines against leishmaniasis is still a major challenge.
      These vaccines should control not only parasite progression, but also the
      accompanying pathology, which results from an imbalanced interaction between the
      infectious agent and the human host immune system. Different strategies for
      development of vaccines are currently under investigation. They range from the
      use of live non-pathogenic vectors to the employment of subunit vaccines combined
      with adjuvants and/or delivery systems inducing cell-mediated immunity.

PMID- 29589967
TI  - Affect-Aware Adaptive Tutoring Based on Human-Automation Etiquette Strategies.
AB  - OBJECTIVE: We investigated adapting the interaction style of intelligent tutoring
      system (ITS) feedback based on human-automation etiquette strategies. BACKGROUND:
      Most ITSs adapt the content difficulty level, adapt the feedback timing, or
      provide extra content when they detect cognitive or affective decrements. Our
      previous work demonstrated that changing the interaction style via different
      feedback etiquette strategies has differential effects on students' motivation,
      confidence, satisfaction, and performance. The best etiquette strategy was also
      determined by user frustration. METHOD: Based on these findings, a rule set was
      developed that systemically selected the proper etiquette strategy to address one
      of four learning factors (motivation, confidence, satisfaction, and performance)
      under two different levels of user frustration. We explored whether etiquette
      strategy selection based on this rule set (systematic) or random changes in
      etiquette strategy for a given level of frustration affected the four learning
      factors. Participants solved mathematics problems under different frustration
      conditions with feedback that adapted dynamic changes in etiquette strategies
      either systematically or randomly. RESULTS: The results demonstrated that
      feedback with etiquette strategies chosen systematically via the rule set could
      selectively target and improve motivation, confidence, satisfaction, and
      performance more than changing etiquette strategies randomly. The systematic
      adaptation was effective no matter the level of frustration for the participant.
      CONCLUSION: If computer tutors can vary the interaction style to effectively
      mitigate negative emotions, then ITS designers would have one more mechanism in
      which to design affect-aware adaptations that provide the proper responses in
      situations where human emotions affect the ability to learn.

PMID- 29589968
TI  - Radiographic features of lingual mandibular bone depression using dental cone
      beam computed tomography.
AB  - OBJECTIVES: To describe accurately the radiographic characteristics of lingual
      mandibular bone depression (LMBD) using CBCT images. METHODS: This study included
      30 cases of LMBD with CBCT images from 29 patients. Age, sex, location, shape,
      size, and the relationships of the LMBDs to adjacent anatomical structures such
      as the mandibular inferior cortex and mandibular canal were recorded. The
      correlation between age and size was evaluated using Pearson's correlation
      coefficient. RESULTS: The average age of the patients was 57 years. LMBDs
      occurred primarily in males (93%), occurrence in the right (n = 14) and left (n =
      16) mandibles was approximately equal. The shapes were ovoid, round, peanut,
      triangular, or rectangular on panoramic radiographs. The occurrences in the
      molar, distal to the molar, and ramus regions were 63.3, 33.3, and 3.3%
      respectively. The mean size on CBCT was 15.4 mm in length, 11.2 mm in height, and
      6.4 mm in depth. The relationship to the mandibular canal was categorized as
      separated (48.2%), contacted (31%), or go-through (20.7%). The relationship to
      the mandibular inferior cortex was classified as separated (20.7%), contacted
      (27.6%), or resorbed (51.7%). The Pearson's correlation coefficient showed a
      positive correlation between age and depth (r = 0.38; p = 0.038). CONCLUSIONS:
      The typical features of a LMBD were ovoid, round or mutilobated radiolucent
      shape, well-defined sclerotic border, and position in the posterior area of the
      mandible between the mandibular canal and inferior mandibular cortex. The
      buccolingual depth of LMBD was deeper with increasing age.

PMID- 29589969
TI  - Checkpoint inhibitors and acute myelogenous leukemia: promises and challenges.
AB  - INTRODUCTION: Immunity, for treatment of acute myelogenous leukemia (AML), has
      been leveraged historically in the form of allogeneic stem cell transplantation.
      Checkpoint inhibitors (CPI) as positive modulators of immune response have been
      recent major breakthroughs in solid tumors. Areas covered: Emerging concepts and
      clinical data with CPIs in acute Myeloid Leukemia - the focus of this review-
      will be discussed. CPIs can potentially be effective in absence of 'actionable'
      mutations and are expected to be effective against poor-risk AML. Immune
      inhibitory checkpoint molecules are upregulated in both de novo and relapsed AML.
      Similar data also suggest role of checkpoint molecules in mediating resistance
      particularly to hypomethylating agent (HMA) therapy, which can potentially be
      reversed by using checkpoint inhibitors. Expert commentary: Ongoing clinical
      trials in combination with HMAs are showing early promise, with doubling of
      response than that seen in historic controls. The optimal combinations of CPIs
      and the optimal space that they will fit in the continuum of AML therapies need
      lot of in depth work.

PMID- 29589970
TI  - Imaging of the Tibionavicular Ligament, and Its Potential Role in Adult Acquired
      Flatfoot Deformity.
AB  - BACKGROUND: The spring ligament is an important medial arch stabilizer. However,
      when disrupted, it does not cause planovalgus deformity until the foot is
      cyclically loaded. We propose that the tibionavicular (TN) ligament plays an
      important role. However, this ligament is not imaged in routine magnetic
      resonance imaging (MRI) sequences. METHODS: A prospective case-control study
      using a novel MRI sequence to image the TN ligament in 20 normal feet creating a
      baseline appearance of the ligament. We then scanned 20 patients with adult
      acquired flatfoot deformity (AAFD). All patients had weightbearing
      anteroposterior and lateral radiographs. We followed up patients, the end point
      being surgery or 18 months' follow-up. RESULTS: The normal ligament was reliably
      identified on the novel sequences. It had a reproducible appearance in 2 views,
      and consistent length and width. Two groups of patients were identified in the
      AAFD cohort: Normal TN (11/20) (The mean Meary angle was 6.8 degrees) and
      Abnormal TN (9/20). The ligament was thickened proximally, with distal
      attenuation and intrasubstance edema. On sagittal sequence, it had dorsal bulging
      and high signal. The mean Meary angle was 13.2 degrees ( P = .013). All patients
      had posterior tibial tendon dysfunction and 8 had spring ligament complex
      attenuation. Five patients have undergone corrective surgery compared to none in
      the other group. CONCLUSION: This study adds to the evidence that AAFD is
      multifactorial. With this imaging technique, we were able to reliably image the
      TN ligament. We hope that including this sequence into routine scanning will help
      us understand its role in flatfoot deformity. This poses the question of whether
      this structure will play a role in reconstructive surgery in future. LEVEL OF
      EVIDENCE: Level II, prospective comparative study.

PMID- 29589971
TI  - Clinical considerations in the hematopoietic stem cell transplant management of
      primary immunodeficiencies.
AB  - INTRODUCTION: Primary immunodeficiencies (PID) are genetic immune disorders
      causing increased predisposition to infections and autoimmunity. The only
      curative procedure is hematopoietic stem cell transplantation (HSCT), results
      from which have improved dramatically since 2000. Complications remain a serious
      issue, especially in HLA non-identical transplantation. In PID patients,
      persistent infection and autoimmunity with end-organ damage cause particular
      problems with approach to transplantation. This article examines these,
      emphasising approach to management and consequences. Areas covered: It is
      challenging to know which patients should be offered HSCT. As new diseases are
      discovered, data are required to determine natural history, and HSCT outcomes.
      Treatment of adults can be challenging, although HSCT outcomes are encouraging.
      New methods of T-lymphocyte depletion show results comparable to those of matched
      sibling donor transplants. New cellular therapies to treat viral infections show
      promising results, and immunomodulatory methods are successful in treating acute
      graft-versus-host disease. Expert commentary: New T-lymphocyte depletion methods
      are a paradigm shift in approach to HSCT for PID. In combination with new
      cellular approaches to treating viral infection, immunomodulatory approaches to
      acute graft-versus-host disease and better understanding of endothelial
      activation syndromes, survival approaches 90%. Widespread introduction of newborn
      screening for severe combined immunodeficiencies will improve survival further.

PMID- 29589972
TI  - Beyond "Facebook Addiction": The Role of Cognitive-Related Factors and
      Psychiatric Distress in Social Networking Site Addiction.
AB  - The use of social networking sites (SNSs) is rapidly increasing as billions of
      individuals use SNS platforms regularly to communicate with other users, follow
      the news, and play browser games. Given the widespread use of SNS platforms,
      investigating the potential predictors of addictive SNS use beyond Facebook use
      has become paramount given that most studies so far focused on "Facebook
      addiction." In this study, a total of 511 English-speaking SNS users (58.1% young
      adults aged 20-35 years; 64.6% female) were recruited online and asked to
      complete a battery of standardized psychometric tools assessing participants'
      sociodemographic characteristics, SNS preferences and patterns of use, SNS
      addiction, preference for online social interaction, maladaptive cognitions, fear
      of missing out (FoMo), dysfunctional emotion regulation, and general psychiatric
      distress. Overall, about 4.9% (n = 25) of all participants could be classed as
      having a high SNS addiction risk profile. Moreover, the results further indicated
      that FoMo (beta = 0.38), maladaptive cognitions (beta = 0.25), and psychiatric
      distress (beta = 0.12) significantly predicted SNS addiction (i.e., p < 0.0001)
      and accounted for about 61% of the total variance in SNS addiction, with FoMo
      providing the strongest predictive contribution over and above the effects of
      sociodemographic variables and patterns of SNS use. The implications of the
      present findings were discussed in light of extant literature on behavioral
      addictions and Facebook addiction and further considerations were provided
      regarding the potential clinical implications for cognitive-based psychological
      treatment approaches to SNS addiction.

PMID- 29589973
TI  - Engineered Ribosomes for Basic Science and Synthetic Biology.
AB  - The ribosome is the cell's factory for protein synthesis. With protein synthesis
      rates of up to 20 amino acids per second and at an accuracy of 99.99%, the
      extraordinary catalytic capacity of the bacterial translation machinery has
      attracted extensive efforts to engineer, reconstruct, and repurpose it for
      biochemical studies and novel functions. Despite these efforts, the potential for
      harnessing the translation apparatus to manufacture bio-based products beyond
      natural limits remains underexploited, and fundamental constraints on the
      chemistry that the ribosome's RNA-based active site can carry out are unknown.
      This review aims to cover the past and present advances in ribosome design and
      engineering to understand the fundamental biology of the ribosome to facilitate
      the construction of synthetic manufacturing machines. The prospects for the
      development of engineered, or designer, ribosomes for novel polymer synthesis are
      reviewed, future challenges are considered, and promising advances in a variety
      of applications are discussed.

PMID- 29589974
TI  - Coronary chronic total occlusion intervention: utility or futility.
AB  - INTRODUCTION: Despite an incidence of about 18-52% of the patients undergoing
      coronary angiography, chronic total occlusions (CTO) are rarely revascularised by
      percutaneous angioplasty (PCI). Nevertheless, current evidence suggests that
      successful CTO angioplasty improves symptoms, quality of life and long-term
      survival. During the last decade, the improvement of specific tools and
      techniques for these complex procedures, and the increasing experience of
      operators, have led to the achievement of success and complication rates almost
      equivalent to non-CTO angioplasty. Areas covered: This review focuses on the
      clinical benefits of CTO revascularization and on appropriate patient selection.
      Expert commentary: Current evidence suggests that successful CTO-PCI improves
      symptoms, quality of life and long-term survival. During the last years, the
      improvement of specific techniques for these complex procedures and the
      increasing experience of operators, have led to the achievement of success and
      complication rates almost equivalent to non-CTO lesion angioplasty.

PMID- 29589975
TI  - The Photochemistry of Unprotected DNA and DNA inside Bacillus subtilis Spores
      Exposed to Simulated Martian Surface Conditions of Atmospheric Composition,
      Temperature, Pressure, and Solar Radiation.
AB  - DNA is considered a potential biomarker for life-detection experiments destined
      for Mars. Experiments were conducted to examine the photochemistry of bacterial
      DNA, either unprotected or within Bacillus subtilis spores, in response to
      exposure to simulated martian surface conditions consisting of the following:
      temperature (-10 degrees C), pressure (0.7 kPa), atmospheric composition [CO2
      (95.54%), N2 (2.7%), Ar (1.6%), O2 (0.13%), and H2O (0.03%)], and UV-visible-near
      IR solar radiation spectrum (200-1100 nm) calibrated to 4 W/m2 of UVC (200-280
      nm). While the majority (99.9%) of viable spores deposited in multiple layers on
      spacecraft-qualified aluminum coupons were inactivated within 5 min, a detectable
      fraction survived for up to the equivalent of ~115 martian sols. Spore
      photoproduct (SP) was the major lesion detected in spore DNA, with minor amounts
      of cyclobutane pyrimidine dimers (CPD), in the order TT CPD > TC CPD >> CT CPD.
      In addition, the (6-4)TC, but not the (6-4)TT, photoproduct was detected in spore
      DNA. When unprotected DNA was exposed to simulated martian conditions, all
      photoproducts were detected. Surprisingly, the (6-4)TC photoproduct was the major
      photoproduct, followed by SP ~ TT CPD > TC CPD > (6-4)TT > CT CPD > CC CPD.
      Differences in the photochemistry of unprotected DNA and spore DNA in response to
      simulated martian surface conditions versus laboratory conditions are reviewed
      and discussed. The results have implications for the planning of future life
      detection experiments that use DNA as the target, and for the long-term
      persistence on Mars of forward contaminants or their DNA. Key Words: Bacillus
      subtilis-DNA-Mars-Photochemistry-Spore-Ultraviolet. Astrobiology 18, 393-402.

PMID- 29589977
TI  - A Meta-analysis of antihypertensive effect of telmisartan versus candesartan in
      patients with essential hypertension.
AB  - OBJECTIVE: The comparison of antihypertensive effects between telmisartan and
      candesartan in patients with essential hypertension has been investigated in
      several small studies. The results were not consistent. We performed this meta
      analysis determining the antihypertensive effect of telmisartan versus
      candesartan in these patients. METHODS: We searched Pubmed, Web of Science, and
      Cochrane Central for all published studies comparing the antihypertensive effects
      between telmisartan and candesartan in patients with essential hypertension.
      RESULTS: The antihypertensive effects were assessed in 302 patients included in 4
      trials with a mean follow-up of 10 +/- 4 weeks. There were no significant
      differences between telmisartan and candesartan in reduction of systolic blood
      pressure (SBP) and diastolic BP (DBP) in patients with essential hypertension
      (weighted mean differences (WMD) for SBP 1.98 mm Hg (95% confidence interval
      (CI), -0.53, 4.49), p > 0.05; WMD for DBP 0.26 mm Hg (95% CI, -1.65, 2.16), p >
      0.05), respectively. In a sub-analysis including 2 randomized studies, there was
      not a significant difference for the reduction of SBP (WMD 0.90 (95% CI, -2.88,
      4.68) mm Hg, p > 0.05) or DBP (WMD -0.80 (95% CI, -3.40, 1.81) mm Hg, p > 0.05)
      treated with telmisartan or candesartan. CONCLUSIONS: This meta-analysis provides
      the evidence that the antihypertensive effects of telmisartan and candesartan are
      similar on SBP and DBP reduction in patients with essential hypertension,
      suggesting that strict designed randomized controlled trial would be helpful to
      compare antihypertensive effects of angiotensin II receptor blockers (ARBs) and
      improve the choice of ARBs in antihypertensive therapy.

PMID- 29589978
TI  - ZAP70 expression enhances chemokine-driven chronic lymphocytic leukemia cell
      migration and arrest by valency regulation of integrins.
AB  - The zeta-associated protein of 70 kDa (ZAP70) is expressed in the aggressive form
      of B-cell chronic lymphocytic leukemia (CLL). Moreover, the integrin very late
      antigen (VLA)-1 is highly expressed on subtypes of CLL that are associated with
      high proliferation rates in the lymph node context. We herein identify a critical
      role for ZAP70 in chemokine-mediated, inside-out signaling to integrins in
      trisomy 12 carrying Ohio State University-CLL cell lines derived from a patient
      with previously treated CLL. We found that ZAP70-positive CLL cells migrated
      significantly better toward ligands of the lymph node homing chemokine receptors
      CCR7 and CXCR4 compared with ZAP70-negative cells. In addition, ZAP70-expressing
      CLL cells adhered more efficiently to integrin ligands under static conditions.
      We discovered that ZAP70 expression controls chemokine-driven clustering of the
      integrins VLA-4 and lymphocyte function-associated antigen-1. More precisely,
      chemokine stimulation resulted in a ZAP70-dependent integrin valency regulation
      on CLL cells, whereas high-affinity regulation of integrins was independent of
      ZAP70. Consequently, ZAP70-expressing CLL cells show increased chemokine-driven
      arrest on immobilized integrin ligands and on chemokine-presenting endothelial
      cells under physiologic flow conditions. Hence, we describe a novel mechanism
      showing how ZAP70 controls chemokine-driven valency regulation of integrins and
      arrest of CLL cells on endothelial cells, a process that might contribute to CLL
      disease progression.-Laufer, J. M., Lyck, R., Legler, D. F. ZAP70 expression
      enhances chemokine-driven chronic lymphocytic leukemia cell migration and arrest
      by valency regulation of integrins.

PMID- 29589976
TI  - The transluminal attenuation gradient in coronary CT angiography for the
      detection of hemodynamically significant disease: can all arteries be treated
      equally?
AB  - OBJECTIVE: Results of the use of the transluminal attenuation gradient (TAG) at
      coronary CT angiography (CCTA) to predict hemodynamically significant disease
      vary widely. This study tested whether diagnostic performance of TAG to predict
      fractional flow reserve (FFR) <= 0.8 is improved when applied separately to
      subsets of coronary arteries that carry similar physiological flow. METHODS: 28
      patients with 64 * 0.5 mm CCTA and invasive FFR in >=1 major coronary artery were
      retrospectively evaluated. Two readers assessed TAG in each artery. The receiver
      operating characteristic (ROC) area under the curve (AUC) was used to assess the
      diagnostic performance of TAG to detect hemodynamically significant disease
      following a clinical use rule [negative: FFR > 0.8 or <= 25% diameter stenosis
      (DS) at invasive catheter angiography; positive: FFR <= 0.8 or >= 90% DS at
      invasive catheter angiography]. ROC AUC was compared for all arteries pooled
      together, vs separately for arteries carrying similar physiological flow (Group
      1: all left anterior descending plus right-dominant left circumflex; Group 2:
      right-dominant RCA plus left/co-dominant left circumflex). RESULTS: Of the 84
      arteries, 30 had FFR measurements, 30 had <=25% DS and 13 had >=90% DS. 11
      arteries with 26-89% DS and no FFR measurement were excluded. TAG interobserver
      reproducibility was excellent (Pearson r = 0.954, Bland-Altman bias: 0.224
      Hounsfield unit cm-1). ROC AUC to detect hemodynamically significant disease was
      higher when considering arteries separately (Group 1 AUC = 0.841, p = 0.039;
      Group 2 AUC = 0.840, p = 0.188), than when pooling all arteries together (AUC =
      0.661). CONCLUSION: Incorporating information on the physiology of coronary flow
      via the particular vessel interrogated and coronary dominance may improve the
      accuracy of TAG, a simple measurement that can be quickly performed at the time
      of CCTA interpretation to detect hemodynamically significant stenosis in
      individual coronary arteries. Advances in knowledge: The interpretation of TAG
      may benefit by incorporating information regarding which coronary artery is being
      interrogated.

PMID- 29589979
TI  - Impact of Orofacial Dysfunction on the Quality of Life of Adult Patients With
      Cleft Lip and Palate.
AB  - OBJECTIVE: This study assessed the prevalence of orofacial dysfunctions (ODs) and
      quality of life (QoL) in adults with and without a cleft lip and palate. DESIGN:
      Cross sectional. SETTING: Craniofacial Center, Hospital for Rehabilitation of
      Craniofacial Anomalies, Bauru, Sao Paulo, Brazil. METHODS: The study was composed
      of a sample of 120 patients: 60 adults in the cleft lip and palate group (CLPG)
      and 60 adults in the control group with no craniofacial anomalies. Each patient
      underwent an interview and clinical examination, using the Nordic Orofacial Test
      Screening (NOT-S) and the 36-Item Short Form Survey. Data were analyzed using
      Mann-Whitney U test, chi2, and the Spearman correlation coefficients. RESULTS:
      There was a higher prevalence of OD in CLPG ( P < .001) on the NOT-S. The adults
      in the CLPG had higher QoL in the areas of general health ( P = .003), physical
      function ( P = .014), social function ( P < .001), and vitality ( P = .006). The
      CLPG had significant associations between higher OD and lower QoL for general
      health ( P = .004), emotional role function ( P = .028), and vitality ( P = .05).
      CONCLUSION: Orofacial dysfunctions were more prevalent in adults with a cleft,
      negatively impacting their QoL in general health, emotional role function, and
      vitality. However, adults with a cleft also had significantly higher QoL,
      reflecting possible resiliency when compared to adults without a cleft.

PMID- 29589981
TI  - Guideline Values for Minimum Nasal Cross-Sectional Area in Children.
AB  - OBJECTIVE: The purpose was to determine age-specific values of the minimum cross
      sectional area of the nasal airway in children without cleft lip or palate and to
      assess whether gender differences occur with growth in order to develop
      guidelines for assessment in children with clefts. PARTICIPANTS: All
      schoolchildren aged 8 to 17 years who met the research criteria were studied
      during rest breathing using the pressure-flow technique. The children came from a
      rural area of 3800 inhabitants. Consecutive age cohorts were used for
      comparisons. RESULTS: Nasal cross-sectional area increased in females from 0.38
      cm2 in 8-year-olds to 0.58 cm2 in 17-year-olds. There was a decrease in size at
      ages 10 to 11 and 14 to 15 years. In males, the area increased from 0.40 to 0.68
      cm2 and decreased slightly from 9 to 10 and 14 to 15 years. The annual changes
      were statistically significant in females between 8 and 9 and 11 to 13 years of
      age, and in males from 11 to 12, 13 to 14, and 15 to 17 years of age. Across
      gender, the only significant difference occurred at age 16. CONCLUSIONS: Our
      results indicate that the increase in nasal airway size is not consistent during
      growth. Nasal airway size showed almost equal values for both genders in young
      children but was systematically larger in boys from 14 years of age on. The
      results refer that by 17 years of age nasal airway may not have reached adult
      size in males.

PMID- 29589980
TI  - Le Fort III Distraction With Internal vs External Distractors: A Cephalometric
      Analysis.
AB  - OBJECTIVE: This study compares the change in midface position following Le Fort
      III advancement using either rigid external distraction (group 1) or internal
      distraction (group 2). We hypothesized that, with reference to right-facing
      cephalometry, internal distraction would result in increased clockwise rotation
      and inferior displacement of the midface. DESIGN: Le Fort III osteotomies and
      standardized distraction protocols were performed on 10 cadaveric specimens per
      group. Right-facing lateral cephalograms were traced and compared across time
      points to determine change in position at points orbitale, anterior nasal spine
      (ANS), A-point, and angle ANB. SETTING: Institutional. PATIENTS, PARTICIPANTS:
      Twenty cadaveric head specimens. INTERVENTIONS: Standard subcranial Le Fort III
      osteotomies were performed from a coronal approach and adequately mobilized. The
      specified distraction mechanism was applied and advanced by 15 mm. MAIN OUTCOME
      MEASURE(S): Changes of position were calculated at various skeletal landmarks:
      orbitale, ANS, A-point, and ANB. RESULTS: Group 1 demonstrated relatively uniform
      x-axis advancement with minimal inferior repositioning at the A-point, ANS, and
      orbitale. Group 2 demonstrated marked variation in x-axis advancement among the 3
      points, along with a significant inferior repositioning and clockwise rotation of
      the midface ( P < .0001). CONCLUSION: External distraction resulted in more
      uniform advancement of the midface, whereas internal distraction resulted in
      greater clockwise rotation and inferior displacement. External distraction
      appears to provide increased vector control of the midface, which is important in
      creating a customized distraction plan based on the patient's individual occlusal
      and skeletal needs.

PMID- 29589982
TI  - Orthodontic Treatment of a Kabuki Syndrome Patient.
AB  - Kabuki syndrome (KS) is a rare disorder characterized by somatic and
      psychological disturbances including special face morphology, skeletal anomalies,
      and other systemic disorders. Because of the diverse clinical manifestation, the
      management of a patient with KS may involve several medical and dental
      specialists, including orthodontics. The aim of the article is to present
      successful orthodontic treatment performed in a 14-year-old boy diagnosed with
      the KS. Dental relations and smile aesthetics were normalized after orthodontic
      treatment; however, problems with patient compliance and cooperation and an
      increased risk of root resorption may influence treatment outcomes.
      Interdisciplinary cooperation between medical and dental specialists is essential
      in patients with KS.

PMID- 29589984
TI  - The Effect of Calcium Dobesilate on Liver Damage in Experimental Obstructive
      Jaundice.
AB  - : Purpose/Aim of the study: Inflammation and oxidative stress are two significant
      factors affecting the degree of liver damage in obstructive jaundice. The aim of
      this study was to evaluate the effect of calcium dobesilate (CaDob), an effective
      antioxidant and anti-inflammatory drug, on damage to liver caused by experimental
      obstructive jaundice. MATERIALS AND METHODS: 30 rats in total were randomly
      placed into three groups, each group consisting of 10 rats. The sham group (Group
      1) only received solely laparotomy. In the control group (Group 2), ligation was
      applied to the biliary tract and no treatment was implemented. In the CaDob group
      (Group 3), following ligation of the biliary tract, 100 mg/kg/day CaDob was
      implemented via an orogastric tube for a 10-day period. Liver tissue and blood
      samples were taken for histopathological and biochemical examination. RESULTS:
      The CaDob group had significantly lower test values for serum liver functions
      when compared to the control group. Statistically lower levels of tissue
      malondialdehyde (MDA) and fluorescent oxidation products (FOP) were detected in
      the CaDob group, and the CaDob group had significantly higher levels of sulfydryl
      (SH) than the control group. Histopathological scores in the CaDob group were
      found out to be statistically less than the scores the control group received (p
      < 0.05). CONCLUSIONS: CaDob treatment repaired the histpatological changes
      induced by bile duct ligation. The hepatoprotective effects of CaDob can be
      associated with its antioxidant properties of the drug.

PMID- 29589983
TI  - A Quality Improvement Initiative to Improve Feeding and Growth of Infants With
      Cleft Lip and/or Palate.
AB  - OBJECTIVE: The purpose of this quality improvement initiative was to improve
      feeding and growth outcomes in infants with cleft lip and/or palate (CL/P).
      DESIGN: Institute for Healthcare Improvement quality improvement model. SETTING:
      Large pediatric academic medical center in the Midwestern United States.
      PARTICIPANTS: One hundred forty-five infants with nonsyndromic CL/P ages 0 to 12
      months. INTERVENTIONS: Key drivers included (1) caregiver education and
      resources, (2) care coordination and flow, and (3) provider education and
      training. Interventions were designed around these themes and included targeting
      improved team communication, increased social work consultations, patient
      tracking, staff education, improved access to feeding equipment, and the launch
      of a new cleft palate feeding team. MAIN OUTCOME MEASURE(S): The primary outcome
      measure was the percentage of new patients with CL/P who met criteria for failure
      to thrive (FTT) per month. The secondary outcome measure was the frequency of
      hospitalization for infants with CL/P with a primary reason for admission of
      feeding difficulties or FTT. RESULTS: The institutional FTT rate for infants with
      CL/P decreased from 17% to 7% ( P < .003). The frequency of hospitalization for
      FTT improved from once every 30 days to once every 118 days. CONCLUSIONS:
      Targeted interventions aimed at improving feeding efficiency and effectiveness,
      as well as changes in care delivery models, can reliably promote improvements in
      feeding and growth outcomes for infants with CL/P, even with psychosocial risk
      factors present.

PMID- 29589985
TI  - A giant dermoid cyst of the orbit.
AB  - To describe a unique case of a non-germinomatous germ cell tumor, a giant orbital
      dermoid, present in adulthood. A 31-year-old male presented in our clinic with
      gradual, painless, progressive proptosis in the left eye since 28 years
      associated with gradual loss of vision. The left eye showed gross proptosis.
      Ocular structures could not be made out. Computed tomography scan showed a well
      circumscribed oval heterogeneous mixed solid and cystic lesion completely filling
      the left orbit with calcification. The differential diagnosis was that of either
      teratoma or optic nerve glioma. The patient underwent excision of the lesion.
      Histopathology revealed a capsulated tumor with multiple cystic components filled
      with blood and eosinophilic material suggestive of a dermoid cyst. Non
      germinomatous germ cell tumors may present atypically in adults and neglected
      benign dermoid cysts can attain massive size mimicking malignant lesions.

PMID- 29589986
TI  - Burning Mouth Pain: A Case Report.

PMID- 29589987
TI  - Molecular Testing Guideline for the Selection of Lung Cancer Patients for
      Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical
      Oncology Endorsement Summary of the College of American
      Pathologists/International Association for the Study of Lung Cancer/Association
      for Molecular Pathology Clinical Practice Guideline Update.

PMID- 29589988
TI  - Laparoscopic Sleeve Gastrectomy for Morbid Obesity at a Veterans Affairs Medical
      Center.
AB  - BACKGROUND: Class III obesity is a global health emergency associated with an
      increase in the incidence of many other diseases such as type 2 diabetes
      mellitus, hypertension, hyperlipidemia, cancer, obstructive sleep apnea,
      nonalcoholic fatty liver disease, osteoarthritis, infertility, and mental health
      disorders. Minimal work has been published regarding the efficacy of laparoscopic
      sleeve gastrectomy (LSG) in the veteran population to surgically manage morbid
      obesity. DESIGN: Retrospective analysis of LSG performed at a Veterans Affairs
      Medical Center (VAMC) between 2010 and 2017. Veterans were followed from their
      enrollment in the bariatric program until twelve months following LSG. The
      primary outcome of interest was excess and total weight loss with resolution of
      associated comorbidities. RESULTS: Excess weight loss at nine and 12 months was
      43.5% and 40.7% and total weight loss was 20.1% and 19.0%, respectively. LSG
      performed at a VAMC resulted in 86.9% improvement in type 2 diabetes mellitus and
      a 66.1% improvement in hypertension and 74.3% improvement in hyperlipidemia.
      Approximately 10.0% of diabetics obtained partial and 9.0% obtained complete
      resolution of their disease. Similarly, 22.0% of Veterans obtained partial and
      13.0% obtained complete resolution from hypertension. Complete resolution from
      hyperlipidemia was achieved in 8.8% of Veterans. There were no postoperative
      complications or staple line leaks. CONCLUSION: LSG is a safe and effective tool
      for morbid obesity with clinical and serological improvements for individuals who
      are unable to lose weight with medical management alone.

PMID- 29589989
TI  - A unique allosteric insulin receptor monoclonal antibody that prevents
      hypoglycemia in the SUR-1-/- mouse model of KATP hyperinsulinism.
AB  - Loss-of-function mutations of the beta-cell ATP-sensitive potassium channels
      (KATP) cause the most common and severe form of congenital hyperinsulinism
      (KATPHI), a disorder of beta-cell function characterized by severe hypoglycemia.
      Children with KATPHI are typically unresponsive to medical therapy and require
      pancreatectomy for intractable hypoglycemia. We tested the hypothesis that
      inhibition of insulin receptor signaling may prevent hypoglycemia in KATPHI. To
      test this hypothesis, we examined the effect of an antibody allosteric inhibitor
      of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of
      KATPHI (SUR-1-/- mice). SUR-1-/- and wild-type mice received twice weekly
      intraperitoneal injections of either XMetD or control antibody for 8 wks.
      Treatment with XMetD significantly decreased insulin sensitivity, and increased
      hepatic glucose output and fasting plasma glucose. These findings support the
      potential use of insulin receptor antagonists as a therapeutic approach to
      control the hypoglycemia in congenital hyperinsulinism.

PMID- 29589990
TI  - Effect of Previous Abdominal Surgery on Laparoscopic Liver Resection: Analysis of
      Feasibility and Risk Factors for Conversion.
AB  - INTRODUCTION: Previous abdominal surgery has traditionally been considered an
      additional element of difficulty to later laparoscopic procedures. The aim of the
      study is to analyze the effect of previous surgery on the feasibility and safety
      of laparoscopic liver resection (LLR), and its role as a risk factor for
      conversion. MATERIALS AND METHODS: After matching, 349 LLR in patients known for
      previous abdominal surgery (PS group) were compared with 349 LLR on patients with
      a virgin abdomen (NPS group). Subgroup analysis included 161 patients with
      previous upper abdominal surgery (UPS subgroup). Feasibility and safety were
      evaluated in terms of conversion rate, reasons for conversion and outcomes, and
      risk factors for conversion assessed via uni/multivariable analysis. RESULTS:
      Conversion rate was 9.4%, and higher for PS patients compared with NPS patients
      (13.7% versus 5.1%, P = .021). Difficult adhesiolysis resulted the commonest
      reason for conversion in PS group (5.7%). However, operative time (P = .840),
      blood loss (P = .270), transfusion (P = .650), morbidity rate (P = .578),
      hospital stay (P = .780), and R1 rate (P = .130) were comparable between PS and
      NPS group. Subgroup analysis confirmed higher conversion rates for UPS patients
      (23%) compared with both NPS (P = .015) and PS patients (P = .041). Previous
      surgery emerged as independent risk factor for conversion (P = .033), alongside
      the postero-superior location and major hepatectomy. CONCLUSION: LLR are feasible
      in case of previous surgery and proved to be safe and maintain the benefits of
      LLR carried out in standard settings. However, a history of surgery should be
      considered a risk factor for conversion.

PMID- 29589992
TI  - Non-cancer, cancer, and dermal sensitization risk assessment of heavy metals in
      cosmetics.
AB  - The heavy metal content of cosmetics may be a cause for concern in that exposure
      to these metals is associated with adverse consequences. Thus, the aim of this
      study was to assess consequences attributed to exposure to heavy metals in
      cosmetics as determined by non-cancer, cancer, and sensitization risks
      methodologies. The quantification and exposure assessments of aluminum (Al),
      chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu),
      zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), antimony (Sb),
      and titanium (Ti) were performed by inductively coupled plasma-mass spectrometry.
      The non-cancer risk assessment of Al, Cr3+, Mn, Fe, Co, Ni, Cu, Zn, Cd, Sb, and
      Ti in cosmetic samples resulted in a margin of safety (MOS) greater than 100 or a
      hazard index (HI) of less than 1. However, the probability of lifetime cancer
      risk (LCR) resulting from dermal exposure to heavy metals from cosmetics exceeded
      the acceptable risk levels (LCR > 10-5). An exposure-based sensitization
      quantitative risk assessment determined that the ratios of acceptable exposure
      level to consumers for Ni, Co, Cu, or Hg were above 1, suggesting an absence of
      skin-sensitizing potential. For an average daily user of lip cosmetics, the
      estimated intakes of heavy metals were within the acceptable daily intake (ADI).
      The percentage of heavy users for which metal intakes exceeded ADIs were 20.37%
      for Pb, 9.26% for Mn, 1.85% for Cr3+, and 1.85% for Cr6+, respectively. Data
      suggested that the heavy metals present in cosmetics do not appear to pose a
      serious risk to health. However, for heavy users of lip cosmetics, contamination
      with some heavy metals, such as Pb, Mn, and Cr needs to be minimized.

PMID- 29589991
TI  - Comparison of patient flow and provider efficiency of two delivery strategies for
      HPV-based cervical cancer screening in Western Kenya: a time and motion study.
AB  - BACKGROUND: Improving patient flow and reducing over-crowding can improve
      quality, promptness of care, and patient satisfaction. Given low utilization of
      preventive care in low-resource countries, improved patient flows are especially
      important in these settings. OBJECTIVE: Compare patient flow and provider
      efficiency between two cervical cancer screening strategies via self-collected
      human papillomavirus (HPV). METHODS: We collected time and motion data for
      patients screened for cervical cancer in 12 communities in rural Migori County,
      Kenya as part of a larger cluster randomized trial. Six communities were
      randomized to screening in community health campaigns (CHCs) and six to screening
      at government clinics. We quantified patient flow: duration spent on each active
      stage of screening and wait times, and the number of patients arriving at CHCs
      and clinics each hour of the day. In addition, for four CHCs, we collected time
      and motion data for providers, and measured provider efficiency as a ratio of
      active (service delivery) time to total time spent at the clinic. RESULTS: Total
      duration of screening visits, at CHCs and clinics was 42 and 87 minutes,
      respectively (p < 0.001 for difference). Total active time lasted longer at CHCs,
      with a mean of 28 minutes per patient versus 15 minutes at clinics, largely due
      to differences in duration for group education (p < 0.001). Wait time for
      registration at clinics was 36 minutes, explaining most of the difference between
      settings, but sometimes incorporated other health services. CONCLUSIONS: There is
      a substantial difference in patient flow at clinics compared to CHCs. Shorter
      duration at CHCs suggests that the model is favorable for patients in limiting
      time spent on screening. Future cervical cancer screening programs designed for
      scale-up should consider how this advantage may enhance satisfaction and uptake.
      For clinic-based screening programs, efforts could be made towards reducing
      registration wait times.

PMID- 29589993
TI  - Incidence of Multidrug-Resistant Organism Among Children Admitted to Pediatric
      Intensive Care Unit in a Developing Country.
AB  - AIM: Multidrug-resistant infections are an increasingly common condition
      particularly in critical care units. This study aimed to determine the incidence
      and types of resistant bacteria acquired in a pediatric intensive care unit
      (PICU) of a university hospital. SUBJECT AND METHODS: A prospective study was
      conducted during the year 2016. All children aged below 16 years were studied for
      infection development and pattern of susceptibility to various groups of
      antibiotics. RESULTS: A total of 264 patients were admitted to the PICU: 16
      patients had community-acquired infection (CAI), 23 had hospital-acquired
      infection, and 24 patients had PICU-acquired infection (with 36 episodes) which
      is equivalent to 14.75 case/1,000 patient days. The study revealed high incidence
      of resistant organisms in the PICU but more important is the appearance of multi-
      and extreme drug-resistant bacteria in CAI. The study revealed that gram-negative
      bacteria were more prevalent in PICU, especially Klebsiella (30.5%),
      Acinetobacter baumanii (22.22%), and Pseudomonas (16.67%). Infection with
      resistant organisms in the PICU caused initial treatment failure and increased
      fourfold risk of mortality. CONCLUSION: The incidence of resistant bacteria
      especially gram-negative pathogens was very high in the PICU. The top three
      resistant organisms of concern were Klebsiella, Acinetobacter, and Pseudomonas.
      This is a global concern that necessitates new strategies.

PMID- 29589994
TI  - Concurrent Milk Ingestion Decreases Absorption of Levothyroxine.
AB  - BACKGROUND: Levothyroxine is the most commonly prescribed medication in the
      United States. Many foods and medications, including calcium supplements, can
      interfere with levothyroxine absorption. No studies have investigated the effect
      of cow's milk, a common breakfast staple, on the absorption of oral
      levothyroxine. Cow's milk contains approximately 450 mg of elemental calcium per
      12 oz (355 mL) serving. METHODS: A pharmacokinetic study was conducted in healthy
      euthyroid subjects to assess levothyroxine absorption with and without concurrent
      cow's milk consumption. Following an overnight fast, serum total thyroxine (TT4)
      concentrations were measured at baseline and at one, two, four, and six hours
      after ingestion of 1000 MUg of oral levothyroxine alone or when co-administered
      with 12 oz (355 mL) of 2% milk. There was a four-week washout period between the
      two assessments in each subject. RESULTS: Ten subjects (Mage +/- SD = 33.7 +/-
      10.2 years; 60% male) completed the study. The area under the curve (AUC) of TT4
      concentrations was significantly lower when levothyroxine was ingested along with
      12 oz (355 mL) of 2% cow's milk (M +/- SD = 67.3 +/- 12.1) compared to that with
      levothyroxine alone (73.5 +/- 17.0; p = 0.02). Also, peak serum TT4
      concentrations were significantly lower when cow's milk was co-administered with
      levothyroxine (M +/- SD = 14.1 +/- 0.8 MUg/dL) than with levothyroxine alone
      (13.0 +/- 0.9 MUg/dL; p = 0.04). CONCLUSIONS: This is the first study to
      demonstrate that concurrent cow's milk ingestion reduces oral levothyroxine
      absorption. The findings support previous literature showing the interference of
      elemental calcium and food with thyroid hormone absorption. Patients managed with
      thyroid hormone should be advised to avoid taking their levothyroxine
      simultaneously with cow's milk.

PMID- 29589995
TI  - The Role of Discrimination in Care Postponement Among Trans-Feminine Individuals
      in the U.S. National Transgender Discrimination Survey.
AB  - PURPOSE: This study examines the associations between discrimination experiences
      (types and locations) and care postponement among trans-feminine individuals in
      the United States. METHODS: This secondary, cross-sectional study utilized a
      subset of the data from the National Transgender Discrimination Survey (n =
      2248), specifically for trans-feminine individuals. In this analysis, we examined
      the relationship between discrimination and primary care postponement. RESULTS:
      Twenty-six percent (26.25%) of the study sample reported delaying preventive care
      due to fear of discrimination; 23.98%-46.66% of respondents reported past
      experiences of discrimination (setting dependent). Discrimination in health and
      non-health settings and different types of discrimination-being denied services,
      verbally harassed, or physically assaulted-were all significantly associated with
      delaying care; respondents reporting discrimination were up to 20 times more
      likely to postpone care. While discrimination at a health location had the
      strongest association with care postponement (adjusted odds ratio = 9.65,
      confidence interval = 7.60-12.24), discrimination in all non-health-related
      locations was also important. Individuals reporting discrimination in greater
      numbers of locations and multiple types of discrimination were more likely to
      postpone care. CONCLUSION: To promote preventive care-seeking, these results
      affirm the importance of interventions that promote discrimination-free
      environments for gender minorities.

PMID- 29589996
TI  - Wealth gradient-based divergence in the prevalence of underweight among women by
      marital status in Quoc Oai district, Vietnam.
AB  - BACKGROUND: The prevalence of underweight is high among women in Asian countries,
      despite nutritional changes in the region. Previous studies have demonstrated
      independent associations between female body weight, marital status and economic
      status. However, few studies have investigated possible interaction between
      marital and economic status in relation to Asian women's body weight. OBJECTIVE:
      This study aimed to test associations between household wealth, marital status
      and underweight among women living in the Quoc Oai district of Vietnam and to
      identify wealth-marital status interaction in relation to body weight in these
      women. METHODS: Data from 1087 women aged 19-60 years were collected via a
      baseline community survey conducted in the Quoc Oai district of Hanoi, Vietnam,
      in 2016. Underweight was defined using an Asian-specific body mass index cut-off
      (<18.5 kg/m2). Marital status was dichotomized into 'never married' and 'ever
      married.' Economic status was measured using household wealth index quintiles.
      Multivariable logistic regressions tested association between wealth and
      underweight after adjusting for marital status and other confounders. An
      interaction term (wealth index*marital status) was fitted to determine whether
      the association between wealth and body weight is modified by marital status.
      RESULTS: Our results show that underweight was independently associated with a
      wealth status (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.79-0.98, p
      = 0.026) and ever-married status (OR: 0.50, 95% CI: 0.34-0.75, p = 0.002). A
      significant interaction effect (OR: 0.67, 95% CI: 0.50-0.90, p = 0.010) indicated
      that wealthy married women were less likely to be underweight, whereas wealthy
      never-married women were more likely to be underweight. CONCLUSIONS: Our results
      suggest that the interaction between wealth and marital status has divergent
      effects on underweight among Asian women. Interventions to reduce underweight
      among Asian women should simultaneously consider economic and marital status.

PMID- 29589998
TI  - Trends in onroad transportation energy and emissions.
AB  - : Globally, 1.3 billion on-road vehicles consume 79 quadrillion BTU of energy,
      mostly gasoline and diesel fuels, emit 5.7 gigatonnes of CO2, and emit other
      pollutants to which approximately 200,000 annual premature deaths are attributed.
      Improved vehicle energy efficiency and emission controls have helped offset
      growth in vehicle activity. New technologies are diffusing into the vehicle fleet
      in response to fuel efficiency and emission standards. Empirical assessment of
      vehicle emissions is challenging because of myriad fuels and technologies,
      intervehicle variability, multiple emission processes, variability in operating
      conditions, and varying capabilities of measurement methods. Fuel economy and
      emissions regulations have been effective in reducing total emissions of key
      pollutants. Real-world fuel use and emissions are consistent with official values
      in the United States but not in Europe or countries that adopt European
      standards. Portable emission measurements systems, which uncovered a recent
      emissions cheating scandal, have a key role in regulatory programs to ensure
      conformity between "real driving emissions" and emission standards. The global
      vehicle fleet will experience tremendous growth, especially in Asia. Although
      existing data and modeling tools are useful, they are often based on convenience
      samples, small sample sizes, large variability, and unquantified uncertainty.
      Vehicles emit precursors to several important secondary pollutants, including
      ozone and secondary organic aerosols, which requires a multipollutant emissions
      and air quality management strategy. Gasoline and diesel are likely to persist as
      key energy sources to mid-century. Adoption of electric vehicles is not a panacea
      with regard to greenhouse gas emissions unless coupled with policies to change
      the power generation mix. Depending on how they are actually implemented and
      used, autonomous vehicles could lead to very large reductions or increases in
      energy consumption. Numerous other trends are addressed with regard to
      technology, emissions controls, vehicle operations, emission measurements,
      impacts on exposure, and impacts on public health. IMPLICATIONS: Without specific
      policies to the contrary, fossil fuels are likely to continue to be the major
      source of on-road vehicle energy consumption. Fuel economy and emission standards
      are generally effective in achieving reductions per unit of vehicle activity.
      However, the number of vehicles and miles traveled will increase. Total energy
      use and emissions depend on factors such as fuels, technologies, land use,
      demographics, economics, road design, vehicle operation, societal values, and
      others that affect demand for transportation, mode choice, energy use, and
      emissions. Thus, there are many opportunities to influence future trends in
      vehicle energy use and emissions.

PMID- 29589997
TI  - Rearing Zebrafish on Black Soldier Fly (Hermetia illucens): Biometric,
      Histological, Spectroscopic, Biochemical, and Molecular Implications.
AB  - A desirable goal of the aquaculture sector is to replace most of fish meal and
      fish oil with more sustainable, cost-effective, and environmental friendly
      ingredients ensuring fish health and welfare standards. Due to minimal
      environmental impact, compared with most conventional feed commodities, insects
      deserve a growing attention as candidate ingredients for aquafeeds. The present
      study investigated, for the first time, the possible application of a 100% insect
      diet in zebrafish larval rearing. Through a multidisciplinary approach, the major
      biological responses of fish to the new diets were assessed. Results of biometry,
      fatty acid composition, expression of genes involved in fish growth, stress
      response, lipid metabolism, chitinolytic activity, gut inflammation, and liver
      macromolecular composition suggested a possible application of insect larvae for
      zebrafish larval rearing. However, further studies are necessary to better
      understand the use of this insect species in the rearing of fish.

PMID- 29589999
TI  - Biguanides Metformin and Phenformin Generate Therapeutic Effects via AMP
      Activated Protein Kinase/Extracellular-Regulated Kinase Pathways in an In Vitro
      Model of Graves' Orbitopathy.
AB  - BACKGROUND: It was hypothesized that the biguanides metformin and phenformin,
      which are anti-hyperglycemic drugs used for diabetes mellitus, would have
      therapeutic effects in an in vitro model of Graves' orbitopathy (GO). Because
      adipogenesis, hyaluronan production, and inflammation are considered important in
      the pathogenesis of GO, this study aimed to determine the therapeutic effects and
      underlying mechanisms of biguanides on these parameters. METHODS: In vitro
      experiments were performed using primary cultured orbital fibroblasts from
      patients with GO. Orbital preadipocyte fibroblasts were allowed to differentiate
      into adipocytes and were treated with various concentrations of metformin or
      phenformin. Oil Red O staining was performed to evaluate lipid accumulation
      within the cells. Western blot analysis was used to measure the expression of
      adipogenic transcription factors and the phosphorylation of AMP-activated protein
      kinase and mitogen-activated protein kinase signaling proteins. Hyaluronan
      production was measured using enzyme-linked immunosorbent assay, and mRNA levels
      of proinflammatory molecules were determined using real-time polymerase chain
      reaction after interleukin (IL)-1beta stimulation with or without biguanide
      treatment. RESULTS: Lipid accumulation during adipogenesis in GO orbital
      fibroblasts was dose-dependently suppressed by both metformin and phenformin.
      Adipocyte differentiation was attenuated, and the adipogenic transcription
      factors peroxisome proliferator-activated receptor gamma and CCAAT-enhancer
      binding proteins-alpha/beta were downregulated. Furthermore, metformin and
      phenformin increased the phosphorylation of AMP-activated protein kinase and
      suppressed extracellular-regulated kinase activation. The IL-1beta-induced
      hyaluronan production and mRNA expression of IL-6, cyclooxygenase-2, and
      intercellular adhesion molecule-1 were also significantly suppressed after
      metformin or phenformin co-treatment. CONCLUSIONS: The present study indicates
      that the biguanides metformin and phenformin exert an anti-adipogenic and
      inhibitory effect on hyaluronan production and expression of pro-inflammatory
      molecules in GO orbital fibroblasts, suggesting that they could potentially be
      used for the treatment of GO.

PMID- 29590000
TI  - Feasibility of remotely-supervised tDCS in a person with neuropathic pain due to
      spinal cord injury.

PMID- 29590001
TI  - Light and Scanning Electron Microscopic Studies of Unionicola tetrafurcatus
      (Acari: Unionicolidae) Infecting Four Freshwater Bivalve Species and
      Histopathological Effect On Its Hosts.
AB  - Water mites of the genus Unionicola are the most common symbionts of freshwater
      bivalves. During the current investigation, a total of 120 live freshwater
      mussels representing 5 species, Corbicula fluminea (Veneroida), Coelatura
      aegyptiaca (Unionoidea), Mutela rostrata, and Chambardia rubens (Mutelidae), were
      collected from 2 localities in Tura (Helwan Governorate) and El Kanater
      (Qaluobiya Governorate), Egypt. Only 3 of the 4 bivalve species listed are
      considered freshwater bivalves (members of Unionoidea). Corbicula fluminea belong
      to the family Cyrenidae within Veneroida. Collected mussels were dissected and
      examined for the presence of unionicolid mites. It was found that 30.83% (37/120)
      were infected with a single mite species, Unionicola tetrafurcatus
      (Unionicolidae). The highest prevalence was observed during the summer with
      83.33% (25/30) whereas the least was observed in autumn, i.e., 33.33% (10/30).
      Mites were recovered from the gills, gonads, and visceral mass of mussel hosts.
      Gills of host mussels were the primary site of oviposition for Unionicola mites.
      Smaller bivalves in size had significantly greater numbers of mites than did
      larger ones in size. Numbers of mites per host species was variable and the
      highest prevalence level of 83.33% (25/30) was recorded in Cor. fluminea while
      the lowest one of 16.66% (5/30) was found in Ch. rubens. Morphological and
      morphometric characterizations of mites revealed some differences between the
      present species and other related Unionicola. Histopathological responses of host
      mussels to the eggs, larvae, and cuticular remnants of U. tetrafurcatus were also
      studied. Therefore, the present study demonstrated that freshwater bivalves have
      a new host and locality records for infection with U. tetrafurcatus. Future
      studies are recommended to include advanced molecular characteristics for these
      mites.

PMID- 29590002
TI  - Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung
      fibrosis in mice.
AB  - Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water.
      Inhalation is an important route of Cd exposure, and lungs are one of the main
      target organs for metal-induced toxicity. Cd inhalation is associated with an
      increased risk of pulmonary diseases. The present study aimed to assess the
      effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene
      guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following
      groups: vehicle control (VC), PHMG, cadmium chloride (CdCl2), and PHMG + CdCl2.
      Animals in the PHMG group exhibited increased numbers of total cells and
      inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by
      inflammation and fibrosis in lung tissues. These parameters were exacerbated in
      mice in the PHMG + CdCl2 group. In contrast, mice in the CdCl2 group alone
      displayed only minimal inflammation in pulmonary tissue. Expression of
      inflammatory cytokines and fibrogenic mediators was significantly elevated in
      lungs of mice in the PHMG group compared with that VC. Further, expression of
      these cytokines and mediators was enhanced in pulmonary tissue in mice
      administered PHMG + CdCl2. Data demonstrate that repeated exposure to low-dose Cd
      may enhance the development of PHMG-induced pulmonary fibrosis.

PMID- 29590004
TI  - Molecular Mechanisms of Colistin Resistance Among Pandrug-Resistant Isolates of
      Acinetobacter baumannii with High Case-Fatality Rate in Intensive Care Unit
      Patients.
AB  - Colistin is considered a last-hope antibiotic against extensively drug-resistant
      isolates of Acinetobacter baumannii. Resistance to colistin has been rarely
      reported for A. baumannii. Genetic alterations in the PmrA-PmrB two-component
      system and lipid A biosynthesis genes may be associated with colistin resistance.
      We investigated molecular mechanisms of colistin resistance in three clinical
      colistin-resistant (ColR) and two colistin-susceptible (ColS) A. baumannii
      isolates. A ColR mutant was generated in vitro by repetitive drug exposure. The
      pmrA, pmrB, lpxA, lpxC, and lpxD genes were amplified and sequenced. To evaluate
      association between colistin resistance and upregulation of pmrCAB operon,
      transcriptional level of the pmrC gene encoding for lipid A phosphoethanolamine
      (PEtN) transferase was quantified by reverse transcription quantitative PCR (RT
      qPCR) analysis. All clinical and in vitro-selected ColR isolates harbored at
      least one point mutation in the pmrB gene, including A142V, P233S, T235I, and
      A227V substitutions as well as duplication of H325. No alteration was found in
      the pmrA and other amino acid substitutions identified in the pmrB as well as lpx
      genes did not seem to be involved in colistin resistance as they were found in
      both ColS and ColR isolates. RT-qPCR analysis revealed a correlation between
      colistin resistance and pmrC overexpression. Specific alterations in the PmrB,
      linked to overproduction of PEtN transferase, triggered colistin resistance in
      the studied A. baumannii isolates.

PMID- 29590003
TI  - Lack of efficacy of transgenic pea (Pisum sativum L.) stably expressing
      antifungal genes against Fusarium spp. in three years of confined field trials.
AB  - Fusarium root rot is a major pea disease in Canada and only partial tolerance
      exists in germplasm. Transgenic technologies may hold promise but the economic
      benefits of genetically modified (GM) pea will need to surpass the regulatory
      costs, time and labor involved in bringing a GM crop to market. European pea
      (Pisum sativum L.) cultivars expressing four antifungal genes, 1-3 beta glucanase
      (G), endochitinase (C) (belonging to PR proteins family), polygalacturonase
      inhibiting proteins (PGIPs) (P) and stilbene synthase (V) have been transformed
      for disease tolerance and showed disease tolerance under laboratory conditions.
      Transgenic lines with four antifungal genes inserted either individually or
      stacked through crossing were tested for their efficacy against Fusarium root rot
      (Fusarium avenaceum) in confined trials over three years (2013 to 2015) in
      comparison with two parental German lines and three Canadian lines. Superior
      emergence, higher fresh weight or lower disease ratings above and below ground,
      of transgenic lines in presence of disease inoculum were not observed
      consistently in the three years of field experiments when compared to the
      parental and Canadian lines in the presence of disease inoculum. No indication of
      an advantage of stacked genes over single genes was observed. Most transgenic
      lines had lower relative gene expression in the roots than in the leaves in
      greenhouse trials suggesting a possible explanation for poor tolerance to
      Fusarium root rot. Field trials are necessary to verify the agronomic performance
      and ecological relevance of the promising effects detected under laboratory
      conditions.

PMID- 29590005
TI  - Religious People Are Trusted Because They Are Viewed as Slow Life-History
      Strategists.
AB  - Religious people are more trusted than nonreligious people. Although most
      theorists attribute these perceptions to the beliefs of religious targets,
      religious individuals also differ in behavioral ways that might cue trust. We
      examined whether perceivers might trust religious targets more because they
      heuristically associate religion with slow life-history strategies. In three
      experiments, we found that religious targets are viewed as slow life-history
      strategists and that these findings are not the result of a universally positive
      halo effect; that the effect of target religion on trust is significantly
      mediated by the target's life-history traits (i.e., perceived reproductive
      strategy); and that when perceivers have direct information about a target's
      reproductive strategy, their ratings of trust are driven primarily by his or her
      reproductive strategy, rather than religion. These effects operate over and above
      targets' belief in moralizing gods and offer a novel theoretical perspective on
      religion and trust.

PMID- 29590006
TI  - Low-Fat Abiraterone Food Effect Is of Little Consequence.

PMID- 29590007
TI  - Prospective International Randomized Phase II Study of Low-Dose Abiraterone With
      Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer.
AB  - Purpose Abiraterone acetate (AA) is a standard of care for metastatic castration
      resistant prostate cancer (CRPC). Despite a large food effect, AA was
      administered under fasting conditions in its pivotal trials. We sought to test
      the hypothesis that low-dose AA (LOW; 250 mg with a low-fat meal) would have
      comparable activity to standard AA (STD; 1,000 mg fasting) in patients with CRPC.
      Patients and Methods Patients (n = 72) with progressive CRPC from seven
      institutions in the United States and Singapore were randomly assigned to STD or
      LOW. Both arms received prednisone 5 mg twice daily. Prostate-specific antigen
      (PSA) was assessed monthly, and testosterone/dehydroepiandrosterone sulfate were
      assessed every 12 weeks with disease burden radiographic assessments. Plasma was
      collected for drug concentrations. Log change in PSA, as a pharmacodynamic
      biomarker for efficacy, was the primary end point, using a noninferiority design.
      Progression-free survival (PFS), PSA response (>= 50% reduction), change in
      androgen levels, and pharmacokinetics were secondary end points. Results Thirty
      six patients were accrued to both arms. At 12 weeks, there was a greater effect
      on PSA in the LOW arm (mean log change, -1.59) compared with STD (-1.19), and
      noninferiority of LOW was established according to predefined criteria. The PSA
      response rate was 58% in LOW and 50% in STD, and the median PFS was approximately
      9 months in both groups. Androgen levels decreased similarly in both arms.
      Although there was no difference in PSA response or PFS, abiraterone
      concentrations were higher in STD. Conclusion Low-dose AA (with low-fat
      breakfast) is noninferior to standard dosing with respect to PSA metrics. Given
      the pharmacoeconomic implications, these data warrant consideration by
      prescribers, payers, and patients. Additional studies are indicated to assess the
      long-term efficacy of this approach.

PMID- 29590008
TI  - Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of
      Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial
      Cancer.
AB  - Purpose In the phase III KEYNOTE-045 study ( ClinicalTrials.gov identifier:
      NCT02256436), pembrolizumab significantly prolonged overall survival compared
      with investigator's choice of chemotherapy in patients with previously treated
      advanced urothelial cancer. Here, we report the results of health-related quality
      of-life (HRQoL) analyses from the KEYNOTE-045 trial. Patients and Methods
      Patients were randomly assigned 1:1 to pembrolizumab 200 mg or investigator's
      choice of docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2
      administered intravenously every 3 weeks. Key prespecified HRQoL analyses were
      time to deterioration (TTD) and mean change from baseline to week 15 in European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
      C30 global health status/quality-of-life score. Results Of 542 patients who were
      randomly assigned, 519 were included in HRQoL analyses (pembrolizumab, n = 266;
      chemotherapy, n = 253). HRQoL compliance was > 95% at baseline and approximately
      88% at week 15 for both groups. Pembrolizumab prolonged TTD in global health
      status/quality-of-life score compared with chemotherapy (median, 3.5 months v 2.3
      months; hazard ratio, 0.72; nominal one-sided P = .004). Mean (95% CI) change
      from baseline to week 15 in global health status/quality-of-life score was 0.69 (
      2.40 to 3.77) with pembrolizumab and -8.36 (-11.84 to -4.89) with chemotherapy
      (mean difference, 9.05 points; 95% CI, 4.61 to 13.50; nominal two-sided P <
      .001). Conclusion Pembrolizumab prolonged TTD in HRQoL compared with
      chemotherapy. Patients who were treated with pembrolizumab had stable or improved
      global health status/quality of life, whereas those who were treated with
      investigator's choice of chemotherapy experienced declines in global health
      status/quality of life. Combined with efficacy and safety outcomes, these data
      support pembrolizumab as standard of care for patients with platinum-refractory
      advanced urothelial cancer.

PMID- 29590009
TI  - From Choosing Wisely to Using Wisely: Increasing the Value of Cancer Care Through
      Clinical Research.

PMID- 29590011
TI  - Chemically induced proximity in biology and medicine.
AB  - Proximity, or the physical closeness of molecules, is a pervasive regulatory
      mechanism in biology. For example, most posttranslational modifications such as
      phosphorylation, methylation, and acetylation promote proximity of molecules to
      play deterministic roles in cellular processes. To understand the role of
      proximity in biologic mechanisms, chemical inducers of proximity (CIPs) were
      developed to synthetically model biologically regulated recruitment. Chemically
      induced proximity allows for precise temporal control of transcription, signaling
      cascades, chromatin regulation, protein folding, localization, and degradation,
      as well as a host of other biologic processes. A systematic analysis of CIPs in
      basic research, coupled with recent technological advances utilizing CRISPR,
      distinguishes roles of causality from coincidence and allows for mathematical
      modeling in synthetic biology. Recently, induced proximity has provided new
      avenues of gene therapy and emerging advances in cancer treatment.

PMID- 29590012
TI  - Comment on "The growth pattern of Neandertals, reconstructed from a juvenile
      skeleton from El Sidron (Spain)".
AB  - Rosas et al (Reports, 22 September 2017, p. 1282) calculate El Sidron J1 to have
      reached only 87.5% of its adult brain size. This finding is based on an
      overestimation of Neandertal brain size. Pairwise comparisons with a larger
      sample of Neandertal fossils reveal that it is unlikely that the brain of El
      Sidron would have grown appreciably larger.

PMID- 29590010
TI  - Mapping mutational effects along the evolutionary landscape of HIV envelope.
AB  - The immediate evolutionary space accessible to HIV is largely determined by how
      single amino acid mutations affect fitness. These mutational effects can shift as
      the virus evolves. However, the prevalence of such shifts in mutational effects
      remains unclear. Here, we quantify the effects on viral growth of all amino acid
      mutations to two HIV envelope (Env) proteins that differ at [Formula: see
      text]100 residues. Most mutations similarly affect both Envs, but the amino acid
      preferences of a minority of sites have clearly shifted. These shifted sites
      usually prefer a specific amino acid in one Env, but tolerate many amino acids in
      the other. Surprisingly, shifts are only slightly enriched at sites that have
      substituted between the Envs-and many occur at residues that do not even contact
      substitutions. Therefore, long-range epistasis can unpredictably shift Env's
      mutational tolerance during HIV evolution, although the amino acid preferences of
      most sites are conserved between moderately diverged viral strains.

PMID- 29590014
TI  - Cover stories: Visualizing the spread of true and false news on social media.

PMID- 29590013
TI  - Response to Comment on "The growth pattern of Neandertals, reconstructed from a
      juvenile skeleton from El Sidron (Spain)".
AB  - The comment by DeSilva challenges our suggestion that brain growth of the El
      Sidron J1 Neandertal was still incomplete at 7.7 years of age. Evidence suggests
      that endocranial volume is likely to represent less than 90% adult size at El
      Sidron as well as Neandertal male plus Krapina samples, in line with further
      evidence from endocranial surface histology and dural sinus groove size.

PMID- 29590016
TI  - News at a glance.

PMID- 29590015
TI  - Health security's blind spot.

PMID- 29590017
TI  - Lithium-sulfur batteries poised for leap.

PMID- 29590018
TI  - Germany's new government makes big promises.

PMID- 29590019
TI  - Saildrone fleet could help replace aging buoys.

PMID- 29590020
TI  - Study undercuts claims of new neurons in adult brains.

PMID- 29590021
TI  - Slow coolant phaseout could worsen warming.

PMID- 29590022
TI  - China hones plans for ambitious x-ray probe.

PMID- 29590023
TI  - Looking for love.

PMID- 29590024
TI  - Fever dilemma.

PMID- 29590025
TI  - The science of fake news.

PMID- 29590026
TI  - Intestinal barriers protect against disease.

PMID- 29590027
TI  - Diverging roads to the heart.

PMID- 29590028
TI  - Harmful networks in the brain and beyond.

PMID- 29590029
TI  - Hemimethylation: DNA's lasting odd couple.

PMID- 29590030
TI  - Will marine productivity wane?

PMID- 29590031
TI  - Capturing dynamic protein interactions.

PMID- 29590032
TI  - Proteoforms as the next proteomics currency.

PMID- 29590033
TI  - The snow leopard's questionable comeback.

PMID- 29590034
TI  - Nigeria's new GDP means scientists suffer.

PMID- 29590035
TI  - Possible brooding of pterosaur parents.

PMID- 29590036
TI  - Refining cell therapy.

PMID- 29590037
TI  - The healing power of painful memories.

PMID- 29590038
TI  - Building better bile ducts.

PMID- 29590039
TI  - Toward a true cure for hearing impairment.

PMID- 29590040
TI  - A liquid-liquid transition in supercooled aqueous solution related to the HDA-LDA
      transition.
AB  - Simulations and theory suggest that the thermodynamic anomalies of water may be
      related to a phase transition between two supercooled liquid states, but so far
      this phase transition has not been observed experimentally because of preemptive
      ice crystallization. We used calorimetry, infrared spectroscopy, and molecular
      dynamics simulations to investigate a water-rich hydrazinium trifluoroacetate
      solution in which the local hydrogen bond structure surrounding a water molecule
      resembles that in neat water at elevated pressure, but which does not crystallize
      upon cooling. Instead, this solution underwent a sharp, reversible phase
      transition between two homogeneous liquid states. The hydrogen-bond structures of
      these two states are similar to those established for high- and low-density
      amorphous (HDA and LDA) water. Such structural similarity supports theories that
      predict a similar sharp transition in pure water under pressure if ice
      crystallization could be suppressed.

PMID- 29590041
TI  - Coherent, atomically thin transition-metal dichalcogenide superlattices with
      engineered strain.
AB  - Epitaxy forms the basis of modern electronics and optoelectronics. We report
      coherent atomically thin superlattices in which different transition metal
      dichalcogenide monolayers-despite large lattice mismatches-are repeated and
      laterally integrated without dislocations within the monolayer plane. Grown by an
      omnidirectional epitaxy, these superlattices display fully matched lattice
      constants across heterointerfaces while maintaining an isotropic lattice
      structure and triangular symmetry. This strong epitaxial strain is precisely
      engineered via the nanoscale supercell dimensions, thereby enabling broad tuning
      of the optical properties and producing photoluminescence peak shifts as large as
      250 millielectron volts. We present theoretical models to explain this coherent
      growth and the energetic interplay governing the ripple formation in these
      strained monolayers. Such coherent superlattices provide building blocks with
      targeted functionalities at the atomically thin limit.

PMID- 29590042
TI  - Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth's deep
      mantle.
AB  - Water-rich regions in Earth's deeper mantle are suspected to play a key role in
      the global water budget and the mobility of heat-generating elements. We show
      that ice-VII occurs as inclusions in natural diamond and serves as an indicator
      for such water-rich regions. Ice-VII, the residue of aqueous fluid present during
      growth of diamond, crystallizes upon ascent of the host diamonds but remains at
      pressures as high as 24 gigapascals; it is now recognized as a mineral by the
      International Mineralogical Association. In particular, ice-VII in diamonds
      points toward fluid-rich locations in the upper transition zone and around the
      660-kilometer boundary.

PMID- 29590043
TI  - Sustained climate warming drives declining marine biological productivity.
AB  - Climate change projections to the year 2100 may miss physical-biogeochemical
      feedbacks that emerge later from the cumulative effects of climate warming. In a
      coupled climate simulation to the year 2300, the westerly winds strengthen and
      shift poleward, surface waters warm, and sea ice disappears, leading to intense
      nutrient trapping in the Southern Ocean. The trapping drives a global-scale
      nutrient redistribution, with net transfer to the deep ocean. Ensuing surface
      nutrient reductions north of 30 degrees S drive steady declines in primary
      production and carbon export (decreases of 24 and 41%, respectively, by 2300).
      Potential fishery yields, constrained by lower-trophic-level productivity,
      decrease by more than 20% globally and by nearly 60% in the North Atlantic.
      Continued high levels of greenhouse gas emissions could suppress marine
      biological productivity for a millennium.

PMID- 29590044
TI  - Local transformations of the hippocampal cognitive map.
AB  - Grid cells are neurons active in multiple fields arranged in a hexagonal lattice
      and are thought to represent the "universal metric for space." However, they
      become nonhomogeneously distorted in polarized enclosures, which challenges this
      view. We found that local changes to the configuration of the enclosure induce
      individual grid fields to shift in a manner inversely related to their distance
      from the reconfigured boundary. The grid remained primarily anchored to the
      unchanged stable walls and showed a nonuniform rescaling. Shifts in
      simultaneously recorded colocalized grid fields were strongly correlated, which
      suggests that the readout of the animal's position might still be intact. Similar
      field shifts were also observed in place and boundary cells-albeit of greater
      magnitude and more pronounced closer to the reconfigured boundary-which suggests
      that there is no simple one-to-one relationship between these three different
      cell types.

PMID- 29590045
TI  - The spread of true and false news online.
AB  - We investigated the differential diffusion of all of the verified true and false
      news stories distributed on Twitter from 2006 to 2017. The data comprise ~126,000
      stories tweeted by ~3 million people more than 4.5 million times. We classified
      news as true or false using information from six independent fact-checking
      organizations that exhibited 95 to 98% agreement on the classifications.
      Falsehood diffused significantly farther, faster, deeper, and more broadly than
      the truth in all categories of information, and the effects were more pronounced
      for false political news than for false news about terrorism, natural disasters,
      science, urban legends, or financial information. We found that false news was
      more novel than true news, which suggests that people were more likely to share
      novel information. Whereas false stories inspired fear, disgust, and surprise in
      replies, true stories inspired anticipation, sadness, joy, and trust. Contrary to
      conventional wisdom, robots accelerated the spread of true and false news at the
      same rate, implying that false news spreads more than the truth because humans,
      not robots, are more likely to spread it.

PMID- 29590048
TI  - Nascent DNA methylome mapping reveals inheritance of hemimethylation at
      CTCF/cohesin sites.
AB  - The faithful inheritance of the epigenome is critical for cells to maintain gene
      expression programs and cellular identity across cell divisions. We mapped strand
      specific DNA methylation after replication forks and show maintenance of the vast
      majority of the DNA methylome within 20 minutes of replication and inheritance of
      some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA
      methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals
      interactions between DNMTs and substrate daughter cytosines en route to
      maintenance methylation or hemimethylation. Finally, we show the inheritance of
      hemiCpGs at short regions flanking CCCTC-binding factor (CTCF)/cohesin binding
      sites in pluripotent cells. Elimination of hemimethylation causes reduced
      frequency of chromatin interactions emanating from these sites, suggesting a role
      for hemimethylation as a stable epigenetic mark regulating CTCF-mediated
      chromatin interactions.

PMID- 29590049
TI  - Why our ways parted.

PMID- 29590046
TI  - Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.
AB  - The gut microbiota benefits humans via short-chain fatty acid (SCFA) production
      from carbohydrate fermentation, and deficiency in SCFA production is associated
      with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of
      specifically designed isoenergetic diets, together with fecal shotgun
      metagenomics, to show that a select group of SCFA-producing strains was promoted
      by dietary fibers and that most other potential producers were either diminished
      or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were
      present in greater diversity and abundance, participants had better improvement
      in hemoglobin A1c levels, partly via increased glucagon-like peptide-1
      production. Promotion of these positive responders diminished producers of
      metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted
      restoration of these SCFA producers may present a novel ecological approach for
      managing T2DM.

PMID- 29590047
TI  - Translocation of a gut pathobiont drives autoimmunity in mice and humans.
AB  - Despite multiple associations between the microbiota and immune diseases, their
      role in autoimmunity is poorly understood. We found that translocation of a gut
      pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues
      triggers autoimmune responses in a genetic background predisposing to
      autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed
      growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and
      T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting
      factors. Pathobiont translocation in monocolonized and autoimmune-prone mice
      induced autoantibodies and caused mortality, which could be prevented by an
      intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was
      recovered from liver biopsies of autoimmune patients, and cocultures with human
      hepatocytes replicated the murine findings; hence, similar processes apparently
      occur in susceptible humans. These discoveries show that a gut pathobiont can
      translocate and promote autoimmunity in genetically predisposed hosts.

PMID- 29590050
TI  - Response to Comment on "Synthesis and characterization of the pentazolate anion
      cyclo-N5- in (N5)6(H3O)3(NH4)4Cl".
AB  - Huang and Xu argue that the cyclo-N5- ion in (N5)6(H3O)3(NH4)4Cl we described in
      our report is theoretically unfavorable and is instead protonated. Their
      conclusion is invalid, as they use an improper method to assess the proton
      transfer in a solid crystal structure. We present an in-depth experimental and
      theoretical analysis of (N5)6(H3O)3(NH4)4Cl that supports the results in the
      original paper.

PMID- 29590051
TI  - Comment on "Synthesis and characterization of the pentazolate anion cyclo-N5- in
      (N5)6(H3O)3(NH4)4Cl".
AB  - Zhang et al (Reports, 27 January 2017, p. 374) reported synthesis of a cyclo-N5-
      ion putatively stabilized in a solid-state salt by hydrogen bonding from
      surrounding counterions. We performed theoretical calculations suggesting that
      HN5 would be favored over the anion in the reported pentazolate salt via proton
      transfer.

PMID- 29590052
TI  - Good gun policy needs research.

PMID- 29590053
TI  - News at a glance.

PMID- 29590054
TI  - Complex behavior arose at dawn of humans.

PMID- 29590055
TI  - Nigeria hit by unprecedented Lassa fever outbreak.

PMID- 29590056
TI  - Vibrations used to talk to quantum circuits.

PMID- 29590057
TI  - Max Planck Society, at a crossroads, seeks new leaders.

PMID- 29590058
TI  - Concern as HIV prevention strategy languishes.

PMID- 29590059
TI  - Master planner.

PMID- 29590060
TI  - Rhythms: The dark side meets the light.

PMID- 29590061
TI  - Circadian organization of the genome.

PMID- 29590062
TI  - A landscape of disgust.

PMID- 29590063
TI  - Logic in babies.

PMID- 29590064
TI  - Random copolymers that protect proteins.

PMID- 29590065
TI  - Beyond PARP-POLtheta as an anticancer target.

PMID- 29590066
TI  - Societal inequalities amplify gender gaps in math.

PMID- 29590067
TI  - Arrival routes of first Americans uncertain.

PMID- 29590068
TI  - Arrival routes of first Americans uncertain-Response.

PMID- 29590069
TI  - Postpublication peer review: A crucial tool.

PMID- 29590071
TI  - Random heteropolymers preserve protein function in foreign environments.
AB  - The successful incorporation of active proteins into synthetic polymers could
      lead to a new class of materials with functions found only in living systems.
      However, proteins rarely function under the conditions suitable for polymer
      processing. On the basis of an analysis of trends in protein sequences and
      characteristic chemical patterns on protein surfaces, we designed four-monomer
      random heteropolymers to mimic intrinsically disordered proteins for protein
      solubilization and stabilization in non-native environments. The heteropolymers,
      with optimized composition and statistical monomer distribution, enable cell-free
      synthesis of membrane proteins with proper protein folding for transport and
      enzyme-containing plastics for toxin bioremediation. Controlling the statistical
      monomer distribution in a heteropolymer, rather than the specific monomer
      sequence, affords a new strategy to interface with biological systems for protein
      based biomaterials.

PMID- 29590070
TI  - Phenotype risk scores identify patients with unrecognized Mendelian disease
      patterns.
AB  - Genetic association studies often examine features independently, potentially
      missing subpopulations with multiple phenotypes that share a single cause. We
      describe an approach that aggregates phenotypes on the basis of patterns
      described by Mendelian diseases. We mapped the clinical features of 1204
      Mendelian diseases into phenotypes captured from the electronic health record
      (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In an
      initial validation, PheRS distinguished cases and controls of five Mendelian
      diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18
      associations between rare variants and phenotypes consistent with Mendelian
      diseases. In 16 patients, the rare genetic variants were associated with severe
      outcomes such as organ transplants. PheRS can augment rare-variant interpretation
      and may identify subsets of patients with distinct genetic causes for common
      diseases.

PMID- 29590072
TI  - Real-time imaging of adatom-promoted graphene growth on nickel.
AB  - Single adatoms are expected to participate in many processes occurring at solid
      surfaces, such as the growth of graphene on metals. We demonstrate, both
      experimentally and theoretically, the catalytic role played by single metal
      adatoms during the technologically relevant process of graphene growth on nickel
      (Ni). The catalytic action of individual Ni atoms at the edges of a growing
      graphene flake was directly captured by scanning tunneling microscopy imaging at
      the millisecond time scale, while force field molecular dynamics and density
      functional theory calculations rationalize the experimental observations. Our
      results unveil the mechanism governing the activity of a single-atom catalyst at
      work.

PMID- 29590073
TI  - Organometallic and radical intermediates reveal mechanism of diphthamide
      biosynthesis.
AB  - Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed
      by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S)
      bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid
      freezing, we have captured an organometallic intermediate with an iron-carbon (Fe
      C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the
      substrate protein, elongation factor 2, this intermediate converts to an organic
      radical, formed by addition of the ACP radical to a histidine side chain. Crystal
      structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that
      the carbon of the SAM C-S bond being cleaved is positioned near the unique
      cluster Fe, able to react with the cluster. Our results explain how selective C-S
      bond cleavage is achieved in this radical SAM enzyme.

PMID- 29590074
TI  - Protecting marine mammals, turtles, and birds by rebuilding global fisheries.
AB  - Reductions in global fishing pressure are needed to end overfishing of target
      species and maximize the value of fisheries. We ask whether such reductions would
      also be sufficient to protect non-target species threatened as bycatch. We
      compare changes in fishing pressure needed to maximize profits from 4713 target
      fish stocks-accounting for >75% of global catch-to changes in fishing pressure
      needed to reverse ongoing declines of 20 marine mammal, sea turtle, and seabird
      populations threatened as bycatch. We project that maximizing fishery profits
      would halt or reverse declines of approximately half of these threatened
      populations. Recovering the other populations would require substantially greater
      effort reductions or targeting improvements. Improving commercial fishery
      management could thus yield important collateral benefits for threatened bycatch
      species globally.

PMID- 29590076
TI  - Precursors of logical reasoning in preverbal human infants.
AB  - Infants are able to entertain hypotheses about complex events and to modify them
      rationally when faced with inconsistent evidence. These capacities suggest that
      infants can use elementary logical representations to frame and prune hypotheses.
      By presenting scenes containing ambiguities about the identity of an object, here
      we show that 12- and 19-month-old infants look longer at outcomes that are
      inconsistent with a logical inference necessary to resolve such ambiguities. At
      the moment of a potential deduction, infants' pupils dilated, and their eyes
      moved toward the ambiguous object when inferences could be computed, in contrast
      to transparent scenes not requiring inferences to identify the object. These
      oculomotor markers resembled those of adults inspecting similar scenes,
      suggesting that intuitive and stable logical structures involved in the
      interpretation of dynamic scenes may be part of the fabric of the human mind.

PMID- 29590077
TI  - Factoring stream turbulence into global assessments of nitrogen pollution.
AB  - The discharge of excess nitrogen to streams and rivers poses an existential
      threat to both humans and ecosystems. A seminal study of headwater streams across
      the United States concluded that in-stream removal of nitrate is controlled
      primarily by stream chemistry and biology. Reanalysis of these data reveals that
      stream turbulence (in particular, turbulent mass transfer across the
      concentration boundary layer) imposes a previously unrecognized upper limit on
      the rate at which nitrate is removed from streams. The upper limit closely
      approximates measured nitrate removal rates in streams with low concentrations of
      this pollutant, a discovery that should inform stream restoration designs and
      efforts to assess the effects of nitrogen pollution on receiving water quality
      and the global nitrogen cycle.

PMID- 29590075
TI  - GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent
      gene silencing.
AB  - Malaria is caused by Plasmodium parasites that proliferate in the bloodstream.
      During each replication cycle, some parasites differentiate into gametocytes, the
      only forms able to infect the mosquito vector and transmit malaria. Sexual
      commitment is triggered by activation of AP2-G, the master transcriptional
      regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent
      silencing of ap2-g prevents sexual conversion in proliferating parasites. In this
      study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an
      upstream activator of sexual commitment. We found that GDV1 targeted
      heterochromatin and triggered HP1 eviction, thus derepressing ap2-g Expression of
      GDV1 was responsive to environmental triggers of sexual conversion and controlled
      via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that
      induces sexual differentiation by antagonizing HP1-dependent gene silencing.

PMID- 29590078
TI  - Lysosome activation clears aggregates and enhances quiescent neural stem cell
      activation during aging.
AB  - In the adult brain, the neural stem cell (NSC) pool comprises quiescent and
      activated populations with distinct roles. Transcriptomic analysis revealed that
      quiescent and activated NSCs exhibited differences in their protein homeostasis
      network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained
      large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates,
      and many of these aggregates were stored in large lysosomes. Perturbation of
      lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and
      the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed
      defects in their lysosomes, increased accumulation of protein aggregates, and
      reduced ability to activate. Enhancement of the lysosome pathway in old quiescent
      NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to
      activate, allowing them to regain a more youthful state.

PMID- 29590079
TI  - Mutation dynamics and fitness effects followed in single cells.
AB  - Mutations have been investigated for more than a century but remain difficult to
      observe directly in single cells, which limits the characterization of their
      dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and
      a fluorescent tag of the mismatch repair system in Escherichia coli, we
      visualized the emergence of mutations in single cells, revealing Poissonian
      dynamics. Concomitantly, we tracked the growth and life span of single cells,
      accumulating ~20,000 mutations genome-wide over hundreds of generations. This
      analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed
      a heavy-tailed distribution of fitness effects and were dominated by quasi
      neutral mutations with an average cost of 0.3%. Our approach has enabled the
      investigation of single-cell individuality in mutation rate, mutation fitness
      costs, and mutation interactions.

PMID- 29590080
TI  - Instagram won't solve inequality.

PMID- 29590081
TI  - Metabolic syndrome, leptin-insulin resistance and uric acid: a trinomial foe for
      Algerian city-dweller adolescents' health.
AB  - Background Adolescence is one of the critical periods where increased risk for
      long-term obesity-related complications is an important health concern. This
      highlights the need to perform early diagnostics based on precise biomarkers to
      decrease the risk of complications in adolescents with obesity. Objective To
      determine the relationships between serum levels of uric acid (UA), leptin and
      insulin with metabolic syndrome (MS) components in Algerian adolescents. Subjects
      Nondiabetic adolescents (n = 204). Methods Blood pressure (BP) and anthropometric
      measurements were performed using standardized techniques. Blood samples were
      taken for determination of glycemia, triglyceridemia, uricemia, cholesterolemia,
      leptinemia and insulinemia. Results The rate of MS among an excess weight group
      was 17.4% [95% confidence interval (CI)]. Serum levels of UA, leptin and insulin
      were significantly higher in the excess weight group compared to a normal weight
      group (279.4 +/- 86.05 vs. 204.9 +/- 50.34 MUmol/L and 25.65 +/- 14.01 vs. 4.09
      +/- 2.60 MUg/L, p < 0.001; 24.58 +/- 13.85 vs. 13.34 +/- 6.41 MUIU/L, p < 0.05).
      Serum levels of UA, leptin and insulin were significantly higher in adolescents
      with MS compared to those without MS (304.86 +/- 111.41 vs. 224.72 +/- 77.81
      MUmol/L, 30.26 +/- 12.46 vs. 16.93 +/- 14.97 MUg/L and 30.91 +/- 17.30 vs. 18.71
      +/- 10.14 MUIU/L, p < 0.05, respectively). Significant correlations were found
      between UA and leptin with waist circumference (r = 0.50 and 0.76), diastolic
      blood pressure (r = 0.58 and 0.43), triglycerides (r = 0.42 and 0.35) and high
      density lipoprotein-cholesterol (r = -0.36 and -0.35). Conclusion Serum levels of
      UA and leptin may be useful biomarkers for early diagnosis of the risk of MS in
      our Algerian adolescent population.

PMID- 29590082
TI  - Subchronic oral toxicity study of Habb-e-Suranjan in albino Wistar rats.

PMID- 29590083
TI  - Efficacy of gefitinib and radiotherapy combination in Indonesian patients with
      lung adenocarcinoma.
AB  - INTRODUCTION: Combinations of gefitinib and radiotherapy have been observed to
      have synergistic and anti-proliferative effects on lung cancer in vitro. In the
      clinical setting, patients who presented with respiratory difficulties such as
      superior vena cava syndrome (SVCS), radiotherapy should be given immediately to
      address the emergency while waiting for the results of epidermal growth factor
      receptor (EGFR) mutation test. However, there has been no study that described
      the role of radio-therapy in Indonesian patients with EGFR-mutant lung
      adenocarcinoma. METHODS: This preliminary study aimed to evaluate the efficacy
      and toxicities of gefitinib and radiotherapy combination in lung adenocarcinoma
      patients in Persahabatan National Respiratory Referral Hospital, Jakarta,
      Indonesia. Subjects were consecutively recruited between January 2013 and
      December 2016. RESULTS: Thirty-one lung adenocarcinoma with EGFR mutations were
      enrolled. Most of them were male (51.61%) with a median age of 54.5 years old
      (range 38-70 years old). EGFR mutation characteristics were on exon 21 L858R
      point mutation (61.30%), exon 21 L861Q point mutation (16.12%) and exon 19
      deletion (22.58%). Radiotherapy was given at doses between 30-60 Gy. Among these
      subjects, median progression-free survival (PFS) was 185 days (95%CI; 123.69 -
      246.30), 1-year survival rate (1-yr) was 45.2%, and median overall survival (OS)
      was 300 days (95%CI; 130.94 - 469.06). There were no grade 3/4 hematological and
      nonhematological toxicities recorded. The most frequent grade 1 and 2 non
      hematological toxicities were skin rash, diarrhea, and paronychia that might be
      related to tyrosine kinase inhibitor (TKI). CONCLUSION: The combination of TKI
      with radiation may be considered in EGFR-mutant lung adenocarcinoma subjects.

PMID- 29590084
TI  - Antibacterial secotirucallane triterpenes from the stem bark of Pseudocedrela
      kotschyi.
AB  - The antibacterial-guided investigation of the stem bark extract of Pseudocedrela
      kotschyi led to the isolation of a new secotirucallane triterpene derivative: 4
      hydroxy-3,4-secotirucalla-7,24-dien-3,21-dioic acid (1), together with the known
      one: 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic acid (2) and 3-methyl ester
      3,4-secotirucalla-4(28),7,24-trien-3,21-dioic (3). The structures of the isolated
      compounds were elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy.
      Extracts, fractions and compounds (1-3) were tested in vitro for antibacterial
      activity against two Gram positive bacteria (Bacillus subtilis and Staphylococcus
      aureus ATCC 25923), and two Gram negative bacteria (Escherichia coli S2(1) and
      Pseudomonas aeruginosa). The MeOH extract and the Hex/CH2Cl2 (70:30) fraction
      showed significant levels of activity (MIC=64- 256 MUg/mL) compared with the two
      reference drugs [ciprofloxacin: MIC (0.5-1 MUg/mL) and amoxicillin: MIC (1-128
      MUg/mL)]. Moreover, the compound 2 isolated from this Hex/CH2Cl2 (70:30) fraction
      had the greatest potential value against S. aureus, E. coli and P. aeruginosa,
      with minimum inhibitory concentrations (MIC) ranging from 4-16 MUg/mL.

PMID- 29590085
TI  - Factors affecting mortality in elderly patients who underwent surgery for gastric
      cancer.
AB  - AIM: The aim of this study was to determine factors affecting overall mortality
      in patients over 60 years of age who underwent surgery for gastric cancer in our
      clinic. MATERIAL AND METHODS: Data on histopathological diagnosis (tumor size,
      lymph node status, and number), pathological stage, serum albumin level, tumor
      markers, complete blood count, and demographic information of 109 patients over
      60 years of age who had surgery for gastric cancer between January 2011 and July
      2016 were obtained retrospectively from the patient files. In addition, the
      survival status of all patients were examined and recorded. Metastatic lymph node
      ratio (MLR), red cell distribution width platelet ratio (RPR), neutrophil
      lymphocyte ratio (NLR), plateletlymphocyte ratio (PLR), and prognostic
      nutritional index (PNI) were calculated. RESULTS: On univariate analysis of
      independent parameters, pathological LN number (p = 0.001), MLR (p <0.001), T3 (p
      = 0.001) or T4 (p = 0,006) tumor stage according to TNM system, the presence of
      metastasis (p = 0.063), and male gender (p = 0.066) were found to affect overall
      mortality (OM). On multivariable Cox regression analysis of these results, MLR (p
      = 0.005) and T stage (p = 0.006) was determined to be a statistically significant
      and independent prognostic value. CONCLUSION: In patients over 60 years of age
      who underwent surgery for gastric cancer, the factors affecting mortality were
      determined to be the presence of metastases, number of pathological lymph nodes,
      and male gender. Metastatic lymph node ratio and T1&T2 stage were determined to
      be independent prognostic factors. KEY WORDS: Elderly, Gastric cancer, Mortality,
      Prognostic factor.

PMID- 29590086
TI  - Presence of Spotters Improves Bench Press Performance: A Deception Study.
AB  - Sheridan, A, Marchant, DC, Williams, EL, Jones, HS, Hewitt, PA, and Sparks, SA.
      Presence of spotters improves bench press performance: a deception study. J
      Strength Cond Res XX(X): 000-000, 2017-Resistance exercise is a widely used
      method of physical training in both recreational exercise and athletic
      populations. The use of training partners and spotters during resistance exercise
      is widespread, but little is known about the effect of the presence of these
      individuals on exercise performance. The purpose of the current study was to
      investigate the effect of spotter presence on bench press performance. Twelve
      recreationally trained participants (age, 21.3 +/- 0.8 years, height, 1.82 +/-
      0.1 m, and weight, 84.8 +/- 11.1 kg) performed 2 trials of 3 sets to failure at
      60% of 1 repetition maximum on separate occasions. The 2 trials consisted of
      spotters being explicitly present or hidden from view (deception). During the
      trials, total repetitions (reps), total weight lifted, ratings of perceived
      exertion (RPE), and self-efficacy were measured. Total reps and weight lifted
      were significantly greater with spotters (difference = 4.5 reps, t = 5.68, p <
      0.001 and difference = 209.6 kg, t = 5.65, p < 0.001, respectively). Although RPE
      and local RPE were significantly elevated in the deception trials (difference =
      0.78, f = 6.16, p = 0.030 and difference = 0.81, f = 5.89, p = 0.034,
      respectively), self-efficacy was significantly reduced (difference = 1.58, f =
      26.90, p < 0.001). This study demonstrates that resistance exercise is improved
      by the presence of spotters, which is facilitated by reduced RPE and increased
      self-efficacy. This has important implications for athletes and clients, who
      should perform resistance exercise in the proximity of others, to maximize total
      work performed.

PMID- 29590087
TI  - MicroRNA Expression Profiling of Bone Marrow Mesenchymal Stem Cells in Steroid
      Induced Osteonecrosis of the Femoral Head Associated with Osteogenesis.
AB  - BACKGROUND Steroid-induced osteonecrosis of the femoral head (SONFH) is a common
      orthopedic disease associated with the application of glucocorticoid (GC). In
      this study, we detected the microRNAs (miRNAs) differentially expressed in bone
      marrow mesenchymal stem cells (BMSCs) from SONFH patients, and target gene
      predictions were performed, and the functions of the target genes was verified.
      MATERIAL AND METHODS BMSCs collected from patients with SONFH and femoral neck
      fracture (FNF) constituted the SONFH group (n=3) and FNF (control) group (n=3),
      respectively. MiRNA microarray analysis was utilized to detect the differentially
      expressed miRNAs, and quantitative real-time polymerase chain reaction (qRT-PCR)
      was used to verify the microarray results. The target genes and functions of the
      differentially expressed miRNAs were analyzed using a bioinformatics database.
      RESULTS The microarray results revealed that compared with the control group, 22
      miRNAs were identified differentially expressed in the SONFH group, with 17
      upregulated and 5 downregulated. Further qRT-PCR validation of differentially
      expressed miRNAs confirmed that hsa-miR-601, hsa-miR-452-3p, hsa-miR-647, and hsa
      miR-516b-5p were significantly increased, whereas hsa-miR-122-3p was
      significantly decreased. During osteogenic differentiation, hsa-miR-601, hsa-miR
      452-3p, hsa-miR-647, hsa-miR-516b-5p, and hsa-miR-127-5p were significantly
      downregulated, whereas hsa-miR-122-3p was significantly upregulated, and miRNAs
      showed a converse tendency during adipogenic differentiation. CONCLUSIONS Six
      miRNAs associated with osteogenic and adipogenic differentiation were identified
      differentially expressed in the BMSCs of SONFH patients; these miRNAs may serve
      as novel biomarkers or therapeutic targets for SONFH.

PMID- 29590088
TI  - Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling
      analysis.
AB  - The shape, elongation, division and sporulation (SEDS) proteins are a large
      family of ubiquitous and essential transmembrane enzymes with critical roles in
      bacterial cell wall biology. The exact function of SEDS proteins was for a long
      time poorly understood, but recent work has revealed that the prototypical SEDS
      family member RodA is a peptidoglycan polymerase-a role previously attributed
      exclusively to members of the penicillin-binding protein family. This discovery
      has made RodA and other SEDS proteins promising targets for the development of
      next-generation antibiotics. However, little is known regarding the molecular
      basis of SEDS activity, and no structural data are available for RodA or any
      homologue thereof. Here we report the crystal structure of Thermus thermophilus
      RodA at a resolution of 2.9 A, determined using evolutionary covariance-based
      fold prediction to enable molecular replacement. The structure reveals a ten-pass
      transmembrane fold with large extracellular loops, one of which is partially
      disordered. The protein contains a highly conserved cavity in the transmembrane
      domain, reminiscent of ligand-binding sites in transmembrane receptors.
      Mutagenesis experiments in Bacillus subtilis and Escherichia coli show that
      perturbation of this cavity abolishes RodA function both in vitro and in vivo,
      indicating that this cavity is catalytically essential. These results provide a
      framework for understanding bacterial cell wall synthesis and SEDS protein
      function.

PMID- 29590089
TI  - Whole-organism clone tracing using single-cell sequencing.
AB  - Embryonic development is a crucial period in the life of a multicellular
      organism, during which limited sets of embryonic progenitors produce all cells in
      the adult body. Determining which fate these progenitors acquire in adult tissues
      requires the simultaneous measurement of clonal history and cell identity at
      single-cell resolution, which has been a major challenge. Clonal history has
      traditionally been investigated by microscopically tracking cells during
      development, monitoring the heritable expression of genetically encoded
      fluorescent proteins and, more recently, using next-generation sequencing
      technologies that exploit somatic mutations, microsatellite instability,
      transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP
      recombination. Single-cell transcriptomics provides a powerful platform for
      unbiased cell-type classification. Here we present ScarTrace, a single-cell
      sequencing strategy that enables the simultaneous quantification of clonal
      history and cell type for thousands of cells obtained from different organs of
      the adult zebrafish. Using ScarTrace, we show that a small set of multipotent
      embryonic progenitors generate all haematopoietic cells in the kidney marrow, and
      that many progenitors produce specific cell types in the eyes and brain. In
      addition, we study when embryonic progenitors commit to the left or right eye.
      ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise
      from the same progenitors, and that osteoblast-restricted precursors can produce
      mesenchymal cells during regeneration. Furthermore, we identify resident immune
      cells in the fin with a distinct clonal origin from other blood cell types. We
      envision that similar approaches will have major applications in other
      experimental systems, in which the matching of embryonic clonal origin to adult
      cell type will ultimately allow reconstruction of how the adult body is built
      from a single cell.

PMID- 29590090
TI  - Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.
AB  - Nutrients, such as amino acids and glucose, signal through the Rag GTPases to
      activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3
      regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of
      GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components
      have no sequence homology to other proteins, so the function of GATOR1 at the
      molecular level is currently unknown. Here we used cryo-electron microscopy to
      solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an
      extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3,
      and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that
      our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding
      modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5
      with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas
      weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP
      activity. These data reveal the structure of a component of the nutrient-sensing
      mTORC1 pathway and a non-canonical interaction between a GAP and its substrate
      GTPase.

PMID- 29590091
TI  - A new class of synthetic retinoid antibiotics effective against bacterial
      persisters.
AB  - A challenge in the treatment of Staphylococcus aureus infections is the high
      prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of
      non-growing, dormant 'persister' subpopulations that exhibit high levels of
      tolerance to antibiotics and have a role in chronic or recurrent infections. As
      conventional antibiotics are not effective in the treatment of infections caused
      by such bacteria, novel antibacterial therapeutics are urgently required. Here we
      used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic
      retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by
      disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism
      with gentamicin, and a low probability of resistance selection. All-atom
      molecular dynamics simulations demonstrated that the ability of retinoids to
      penetrate and embed in lipid bilayers correlates with their bactericidal ability.
      An analogue of CD437 was found to retain anti-persister activity and show an
      improved cytotoxicity profile. Both CD437 and this analogue, alone or in
      combination with gentamicin, exhibit considerable efficacy in a mouse model of
      chronic MRSA infection. With further development and optimization, synthetic
      retinoids have the potential to become a new class of antimicrobials for the
      treatment of Gram-positive bacterial infections that are currently difficult to
      cure.

PMID- 29590092
TI  - Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation
      of KEAP1.
AB  - The endogenous metabolite itaconate has recently emerged as a regulator of
      macrophage function, but its precise mechanism of action remains poorly
      understood. Here we show that itaconate is required for the activation of the
      anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by
      lipopolysaccharide in mouse and human macrophages. We find that itaconate
      directly modifies proteins via alkylation of cysteine residues. Itaconate
      alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1,
      enabling Nrf2 to increase the expression of downstream genes with anti-oxidant
      and anti-inflammatory capacities. The activation of Nrf2 is required for the anti
      inflammatory action of itaconate. We describe the use of a new cell-permeable
      itaconate derivative, 4-octyl itaconate, which is protective against
      lipopolysaccharide-induced lethality in vivo and decreases cytokine production.
      We show that type I interferons boost the expression of Irg1 (also known as
      Acod1) and itaconate production. Furthermore, we find that itaconate production
      limits the type I interferon response, indicating a negative feedback loop that
      involves interferons and itaconate. Our findings demonstrate that itaconate is a
      crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and
      modulate type I interferons.

PMID- 29590093
TI  - The logic of single-cell projections from visual cortex.
AB  - Neocortical areas communicate through extensive axonal projections, but the logic
      of information transfer remains poorly understood, because the projections of
      individual neurons have not been systematically characterized. It is not known
      whether individual neurons send projections only to single cortical areas or
      distribute signals across multiple targets. Here we determine the projection
      patterns of 591 individual neurons in the mouse primary visual cortex using whole
      brain fluorescence-based axonal tracing and high-throughput DNA sequencing of
      genetically barcoded neurons (MAPseq). Projections were highly diverse and
      divergent, collectively targeting at least 18 cortical and subcortical areas.
      Most neurons targeted multiple cortical areas, often in non-random combinations,
      suggesting that sub-classes of intracortical projection neurons exist. Our
      results indicate that the dominant mode of intracortical information transfer is
      not based on 'one neuron-one target area' mapping. Instead, signals carried by
      individual cortical neurons are shared across subsets of target areas, and thus
      concurrently contribute to multiple functional pathways.

PMID- 29590094
TI  - Quantized Majorana conductance.
AB  - Majorana zero-modes-a type of localized quasiparticle-hold great promise for
      topological quantum computing. Tunnelling spectroscopy in electrical transport is
      the primary tool for identifying the presence of Majorana zero-modes, for
      instance as a zero-bias peak in differential conductance. The height of the
      Majorana zero-bias peak is predicted to be quantized at the universal conductance
      value of 2e2/h at zero temperature (where e is the charge of an electron and h is
      the Planck constant), as a direct consequence of the famous Majorana symmetry in
      which a particle is its own antiparticle. The Majorana symmetry protects the
      quantization against disorder, interactions and variations in the tunnel
      coupling. Previous experiments, however, have mostly shown zero-bias peaks much
      smaller than 2e2/h, with a recent observation of a peak height close to 2e2/h.
      Here we report a quantized conductance plateau at 2e2/h in the zero-bias
      conductance measured in indium antimonide semiconductor nanowires covered with an
      aluminium superconducting shell. The height of our zero-bias peak remains
      constant despite changing parameters such as the magnetic field and tunnel
      coupling, indicating that it is a quantized conductance plateau. We distinguish
      this quantized Majorana peak from possible non-Majorana origins by investigating
      its robustness to electric and magnetic fields as well as its temperature
      dependence. The observation of a quantized conductance plateau strongly supports
      the existence of Majorana zero-modes in the system, consequently paving the way
      for future braiding experiments that could lead to topological quantum computing.

PMID- 29590095
TI  - Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic
      seizure.
AB  - Experimental recordings in hippocampal slices indicate that astrocytic
      dysfunction may cause neuronal hyper-excitation or seizures. Considering that
      astrocytes play important roles in mediating local uptake and spatial buffering
      of K+ in the extracellular space of the cortical circuit, we constructed a novel
      model of an astrocyte-neuron network module consisting of a single compartment
      neuron and 4 surrounding connected astrocytes and including extracellular
      potassium dynamics. Next, we developed a new model function for the astrocyte gap
      junctions, connecting two astrocyte-neuron network modules. The function form and
      parameters of the gap junction were based on nonlinear regression fitting of a
      set of experimental data published in previous studies. Moreover, we have created
      numerical simulations using the above single astrocyte-neuron network module and
      the coupled astrocyte-neuron network modules. Our model validates previous
      experimental observations that both Kir4.1 channels and gap junctions play
      important roles in regulating the concentration of extracellular potassium. In
      addition, we also observe that changes in Kir4.1 channel conductance and gap
      junction strength induce spontaneous epileptic activity in the absence of
      external stimuli.

PMID- 29590096
TI  - Large scale variation in the rate of germ-line de novo mutation, base
      composition, divergence and diversity in humans.
AB  - It has long been suspected that the rate of mutation varies across the human
      genome at a large scale based on the divergence between humans and other species.
      However, it is now possible to directly investigate this question using the large
      number of de novo mutations (DNMs) that have been discovered in humans through
      the sequencing of trios. We investigate a number of questions pertaining to the
      distribution of mutations using more than 130,000 DNMs from three large datasets.
      We demonstrate that the amount and pattern of variation differs between datasets
      at the 1MB and 100KB scales probably as a consequence of differences in
      sequencing technology and processing. In particular, datasets show different
      patterns of correlation to genomic variables such as replication time. Never-the
      less there are many commonalities between datasets, which likely represent true
      patterns. We show that there is variation in the mutation rate at the 100KB, 1MB
      and 10MB scale that cannot be explained by variation at smaller scales, however
      the level of this variation is modest at large scales-at the 1MB scale we infer
      that ~90% of regions have a mutation rate within 50% of the mean. Different types
      of mutation show similar levels of variation and appear to vary in concert which
      suggests the pattern of mutation is relatively constant across the genome. We
      demonstrate that variation in the mutation rate does not generate large-scale
      variation in GC-content, and hence that mutation bias does not maintain the
      isochore structure of the human genome. We find that genomic features explain
      less than 40% of the explainable variance in the rate of DNM. As expected the
      rate of divergence between species is correlated to the rate of DNM. However, the
      correlations are weaker than expected if all the variation in divergence was due
      to variation in the mutation rate. We provide evidence that this is due the
      effect of biased gene conversion on the probability that a mutation will become
      fixed. In contrast to divergence, we find that most of the variation in diversity
      can be explained by variation in the mutation rate. Finally, we show that the
      correlation between divergence and DNM density declines as increasingly divergent
      species are considered.

PMID- 29590097
TI  - Modeling the dynamics of oligodendrocyte precursor cells and the genesis of
      gliomas.
AB  - Oligodendrocyte precursor cells (OPCs) have remarkable properties: they represent
      the most abundant cycling cell population in the adult normal brain and they
      manage to achieve a uniform and constant density throughout the adult brain. This
      equilibrium is obtained by the interplay of four processes: division,
      differentiation or death, migration and active self-repulsion. They are also
      strongly suspected to be at the origin of gliomas, when their equilibrium is
      disrupted. In this article, we present a model of the dynamics of OPCs, first in
      a normal tissue. This model is based on a cellular automaton and its rules are
      mimicking the ones that regulate the dynamics of real OPCs. The model is able to
      reproduce the homeostasis of the cell population, with the maintenance of a
      constant and uniform cell density and the healing of a lesion. We show that there
      exists a fair quantitative agreement between the simulated and experimental
      parameters, such as the cell velocity, the time taken to close a lesion, and the
      duration of the cell cycle. We present three possible scenarios of disruption of
      the equilibrium: the appearance of an over-proliferating cell, of a deadless/non
      differentiating cell, or of a cell that lost any contact-inhibition. We show that
      the appearance of an over-proliferating cell is sufficient to trigger the growth
      of a tumor that has low-grade glioma features: an invasive behaviour, a linear
      radial growth of the tumor with a corresponding growth velocity of less than 2 mm
      per year, as well a cell density at the center which exceeds the one in normal
      tissue by a factor of less than two. The loss of contact inhibition leads to a
      more high-grade-like glioma. The results of our model contribute to the body of
      evidence that identify OPCs as possible cells of origin of gliomas.

PMID- 29590098
TI  - A chitinase with two catalytic domains is required for organization of the
      cuticular extracellular matrix of a beetle.
AB  - Insect cuticle or exoskeleton is an extracellular matrix formed primarily from
      two different structural biopolymers, chitin and protein. During each molt cycle,
      a new cuticle is deposited simultaneously with degradation of the inner part of
      the chitinous procuticle of the overlying old exoskeleton by molting fluid
      enzymes including epidermal chitinases. In this study we report a novel role for
      an epidermal endochitinase containing two catalytic domains, TcCHT7, from the red
      flour beetle, Tribolium castaneum, in organizing chitin in the newly forming
      cuticle rather than in degrading chitin present in the prior one. Recombinant
      TcCHT7 expressed in insect cells is membrane-bound and capable of hydrolyzing an
      extracellular chitin substrate, whereas in vivo, this enzyme is also released
      from the plasma membrane and co-localizes with chitin in the entire procuticle.
      RNAi of TcCHT7 reveals that this enzyme is nonessential for any type of molt or
      degradation of the chitinous matrix in the old cuticle. In contrast, TcCHT7 is
      required for maintaining the integrity of the cuticle as a compact structure of
      alternating electron-dense and electron-lucent laminae. There is a reduction in
      thickness of elytral and leg cuticles after RNAi for TcCHT7. TcCHT7 is also
      required for formation of properly oriented long chitin fibers inside pore canals
      that are vertically oriented columnar structures, which contribute to the
      mechanical strength of a light-weight, yet rigid, adult cuticle. The conservation
      of CHT7-like proteins harboring such a unique domain configuration among many
      insect and other arthropod species indicates a critical role for the group III
      class of chitinases in the higher ordered organization of chitin fibers for
      development of the structural integrity of many invertebrate exoskeletons.

PMID- 29590099
TI  - Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty
      liver disease in women: A longitudinal study based on a United Kingdom primary
      care database.
AB  - BACKGROUND: Androgen excess is a defining feature of polycystic ovary syndrome
      (PCOS), which affects 10% of women and represents a lifelong metabolic disorder,
      with increased risk of type 2 diabetes, hypertension, and cardiovascular events.
      Previous studies have suggested an increased risk of nonalcoholic fatty liver
      disease (NAFLD) in individuals with PCOS and implicated androgen excess as a
      potential driver. METHODS AND FINDINGS: We carried out a retrospective
      longitudinal cohort study utilizing a large primary care database in the United
      Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body
      mass index (BMI)-, and location-matched control women registered from January
      2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD
      in women with a measurement of serum testosterone (n = 71,061) and sex hormone
      binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate
      the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased
      rate of NAFLD (HR = 2.23, 95% CI 1.86-2.66, p < 0.001), also after adjusting for
      BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an
      increase in NAFLD (HR = 2.30, 95% CI 1.16-4.53, p = 0.017 for 3-3.49 nmol/L and
      HR = 2.40, 95% CI 1.24-4.66, p = 0.009 for >3.5 nmol/L). Mirroring this finding,
      SHBG <30 nmol/L was associated with increased NAFLD hazard (HR = 4.75, 95% CI
      2.44-9.25, p < 0.001 for 20-29.99 nmol/L and HR = 4.98, 95% CI 2.45-10.11, p <
      0.001 for <20 nmol/L). Limitations of this study include its retrospective
      nature, absence of detailed information on criteria used to diagnosis PCOS and
      NAFLD, and absence of data on laboratory assays used to measure serum androgens.
      CONCLUSIONS: We found that women with PCOS have an increased rate of NAFLD. In
      addition to increased BMI and dysglycemia, androgen excess contributes to the
      development of NAFLD in women with PCOS. In women with PCOS-related androgen
      excess, systematic NAFLD screening should be considered.

PMID- 29590101
TI  - Bamgineer: Introduction of simulated allele-specific copy number variants into
      exome and targeted sequence data sets.
AB  - Somatic copy number variations (CNVs) play a crucial role in development of many
      human cancers. The broad availability of next-generation sequencing data has
      enabled the development of algorithms to computationally infer CNV profiles from
      a variety of data types including exome and targeted sequence data; currently the
      most prevalent types of cancer genomics data. However, systemic evaluation and
      comparison of these tools remains challenging due to a lack of ground truth
      reference sets. To address this need, we have developed Bamgineer, a tool written
      in Python to introduce user-defined haplotype-phased allele-specific copy number
      events into an existing Binary Alignment Mapping (BAM) file, with a focus on
      targeted and exome sequencing experiments. As input, this tool requires a read
      alignment file (BAM format), lists of non-overlapping genome coordinates for
      introduction of gains and losses (bed file), and an optional file defining known
      haplotypes (vcf format). To improve runtime performance, Bamgineer introduces the
      desired CNVs in parallel using queuing and parallel processing on a local machine
      or on a high-performance computing cluster. As proof-of-principle, we applied
      Bamgineer to a single high-coverage (mean: 220X) exome sequence file from a blood
      sample to simulate copy number profiles of 3 exemplar tumors from each of 10
      tumor types at 5 tumor cellularity levels (20-100%, 150 BAM files in total). To
      demonstrate feasibility beyond exome data, we introduced read alignments to a
      targeted 5-gene cell-free DNA sequencing library to simulate EGFR amplifications
      at frequencies consistent with circulating tumor DNA (10, 1, 0.1 and 0.01%) while
      retaining the multimodal insert size distribution of the original data. We expect
      Bamgineer to be of use for development and systematic benchmarking of CNV calling
      algorithms by users using locally-generated data for a variety of applications.
      The source code is freely available at http://github.com/pughlab/bamgineer.

PMID- 29590100
TI  - Glial loss of the metallo beta-lactamase domain containing protein, SWIP-10,
      induces age- and glutamate-signaling dependent, dopamine neuron degeneration.
AB  - Across phylogeny, glutamate (Glu) signaling plays a critical role in regulating
      neural excitability, thus supporting many complex behaviors. Perturbed synaptic
      and extrasynaptic Glu homeostasis in the human brain has been implicated in
      multiple neuropsychiatric and neurodegenerative disorders including Parkinson's
      disease, where theories suggest that excitotoxic insults may accelerate a
      naturally occurring process of dopamine (DA) neuron degeneration. In C. elegans,
      mutation of the glial expressed gene, swip-10, results in Glu-dependent DA neuron
      hyperexcitation that leads to elevated DA release, triggering DA signaling
      dependent motor paralysis. Here, we demonstrate that swip-10 mutations induce
      premature and progressive DA neuron degeneration, with light and electron
      microscopy studies demonstrating the presence of dystrophic dendritic processes,
      as well as shrunken and/or missing cell soma. As with paralysis, DA neuron
      degeneration in swip-10 mutants is rescued by glial-specific, but not DA neuron
      specific expression of wildtype swip-10, consistent with a cell non-autonomous
      mechanism. Genetic studies implicate the vesicular Glu transporter VGLU-3 and the
      cystine/Glu exchanger homolog AAT-1 as potential sources of Glu signaling
      supporting DA neuron degeneration. Degeneration can be significantly suppressed
      by mutations in the Ca2+ permeable Glu receptors, nmr-2 and glr-1, in genes that
      support intracellular Ca2+ signaling and Ca2+-dependent proteolysis, as well as
      genes involved in apoptotic cell death. Our studies suggest that Glu stimulation
      of nematode DA neurons in early larval stages, without the protective actions of
      SWIP-10, contributes to insults that ultimately drive DA neuron degeneration. The
      swip-10 model may provide an efficient platform for the identification of
      molecular mechanisms that enhance risk for Parkinson's disease and/or the
      identification of agents that can limit neurodegenerative disease progression.

PMID- 29590102
TI  - Common alpha-globin variants modify hematologic and other clinical phenotypes in
      sickle cell trait and disease.
AB  - Co-inheritance of alpha-thalassemia has a significant protective effect on the
      severity of complications of sickle cell disease (SCD), including stroke.
      However, little information exists on the association and interactions for the
      common African ancestral alpha-thalassemia mutation (-alpha3.7 deletion) and beta
      globin traits (HbS trait [SCT] and HbC trait) on important clinical phenotypes
      such as red blood cell parameters, anemia, and chronic kidney disease (CKD). In a
      community-based cohort of 2,916 African Americans from the Jackson Heart Study,
      we confirmed the expected associations between SCT, HbC trait, and the -alpha3.7
      deletion with lower mean corpuscular volume/mean corpuscular hemoglobin and
      higher red blood cell count and red cell distribution width. In addition to the
      recently recognized association of SCT with lower estimated glomerular filtration
      rate and glycated hemoglobin (HbA1c), we observed a novel association of the 
      alpha3.7 deletion with higher HbA1c levels. Co-inheritance of each additional
      copy of the -alpha3.7 deletion significantly lowered the risk of anemia and
      chronic kidney disease among individuals with SCT (P-interaction = 0.031 and
      0.019, respectively). Furthermore, co-inheritance of a novel alpha-globin
      regulatory variant was associated with normalization of red cell parameters in
      individuals with the -alpha3.7 deletion and significantly negated the protective
      effect of alpha-thalassemia on stroke in 1,139 patients with sickle cell anemia
      from the Cooperative Study of Sickle Cell Disease (CSSCD) (P-interaction =
      0.0049). Functional assays determined that rs11865131, located in the major alpha
      globin enhancer MCS-R2, was the most likely causal variant. These findings
      suggest that common alpha- and beta-globin variants interact to influence
      hematologic and clinical phenotypes in African Americans, with potential
      implications for risk-stratification and counseling of individuals with SCD and
      SCT.

PMID- 29590103
TI  - Preferential retention of genes from one parental genome after polyploidy
      illustrates the nature and scope of the genomic conflicts induced by
      hybridization.
AB  - Polyploidy is increasingly seen as a driver of both evolutionary innovation and
      ecological success. One source of polyploid organisms' successes may be their
      origins in the merging and mixing of genomes from two different species (e.g.,
      allopolyploidy). Using POInT (the Polyploid Orthology Inference Tool), we model
      the resolution of three allopolyploidy events, one from the bakers' yeast
      (Saccharomyces cerevisiae), one from the thale cress (Arabidopsis thaliana) and
      one from grasses including Sorghum bicolor. Analyzing a total of 21 genomes, we
      assign to every gene a probability for having come from each parental subgenome
      (i.e., derived from the diploid progenitor species), yielding orthologous
      segments across all genomes. Our model detects statistically robust evidence for
      the existence of biased fractionation in all three lineages, whereby genes from
      one of the two subgenomes were more likely to be lost than those from the other
      subgenome. We further find that a driver of this pattern of biased losses is the
      co-retention of genes from the same parental genome that share functional
      interactions. The pattern of biased fractionation after the Arabidopsis and grass
      allopolyploid events was surprisingly constant in time, with the same parental
      genome favored throughout the lineages' history. In strong contrast, the yeast
      allopolyploid event shows evidence of biased fractionation only immediately after
      the event, with balanced gene losses more recently. The rapid loss of
      functionally associated genes from a single subgenome is difficult to reconcile
      with the action of genetic drift and suggests that selection may favor the
      removal of specific duplicates. Coupled to the evidence for continuing,
      functionally-associated biased fractionation after the A. thaliana At-alpha
      event, we suggest that, after allopolyploidy, there are functional conflicts
      between interacting genes encoded in different subgenomes that are ultimately
      resolved through preferential duplicate loss.

PMID- 29590104
TI  - Autophagy is essential for maintaining the growth of a human (mini-)organ:
      Evidence from scalp hair follicle organ culture.
AB  - Autophagy plays a crucial role in health and disease, regulating central cellular
      processes such as adaptive stress responses, differentiation, tissue development,
      and homeostasis. However, the role of autophagy in human physiology is poorly
      understood, highlighting a need for a model human organ system to assess the
      efficacy and safety of strategies to therapeutically modulate autophagy. As a
      complete, cyclically remodelled (mini-)organ, the organ culture of human scalp
      hair follicles (HFs), which, after massive growth (anagen), spontaneously enter
      into an apoptosis-driven organ involution (catagen) process, may provide such a
      model. Here, we reveal that in anagen, hair matrix keratinocytes (MKs) of organ
      cultured HFs exhibit an active autophagic flux, as documented by evaluation of
      endogenous lipidated Light Chain 3B (LC3B) and sequestosome 1 (SQSTM1/p62)
      proteins and the ultrastructural visualization of autophagosomes at all stages of
      the autophagy process. This autophagic flux is altered during catagen, and
      genetic inhibition of autophagy promotes catagen development. Conversely, an anti
      hair loss product markedly enhances intrafollicular autophagy, leading to anagen
      prolongation. Collectively, our data reveal a novel role of autophagy in human
      hair growth. Moreover, we show that organ-cultured scalp HFs are an excellent
      preclinical research model for exploring the role of autophagy in human tissue
      physiology and for evaluating the efficacy and tissue toxicity of candidate
      autophagy-modulatory agents in a living human (mini-)organ.

PMID- 29590105
TI  - Effects of multiple sources of genetic drift on pathogen variation within hosts.
AB  - Changes in pathogen genetic variation within hosts alter the severity and spread
      of infectious diseases, with important implications for clinical disease and
      public health. Genetic drift may play a strong role in shaping pathogen
      variation, but analyses of drift in pathogens have oversimplified pathogen
      population dynamics, either by considering dynamics only at a single scale-such
      as within hosts or between hosts-or by making drastic simplifying assumptions,
      for example, that host immune systems can be ignored or that transmission
      bottlenecks are complete. Moreover, previous studies have used genetic data to
      infer the strength of genetic drift, whereas we test whether the genetic drift
      imposed by pathogen population processes can be used to explain genetic data. We
      first constructed and parameterized a mathematical model of gypsy moth
      baculovirus dynamics that allows genetic drift to act within and between hosts.
      We then quantified the genome-wide diversity of baculovirus populations within
      each of 143 field-collected gypsy moth larvae using Illumina sequencing. Finally,
      we determined whether the genetic drift imposed by host-pathogen population
      dynamics in our model explains the levels of pathogen diversity in our data. We
      found that when the model allows drift to act at multiple scales-including within
      hosts, between hosts, and between years-it can accurately reproduce the data, but
      when the effects of drift are simplified by neglecting transmission bottlenecks
      and stochastic variation in virus replication within hosts, the model fails. A de
      novo mutation model and a purifying selection model similarly fail to explain the
      data. Our results show that genetic drift can play a strong role in determining
      pathogen variation and that mathematical models that account for pathogen
      population growth at multiple scales of biological organization can be used to
      explain this variation.

PMID- 29590106
TI  - Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion
      impairing Hsp90 function and overexpression expanding the target space.
AB  - The capacity to respond to temperature fluctuations is critical for
      microorganisms to survive within mammalian hosts, and temperature modulates
      virulence traits of diverse pathogens. One key temperature-dependent virulence
      trait of the fungal pathogen Candida albicans is its ability to transition from
      yeast to filamentous growth, which is induced by environmental cues at host
      physiological temperature. A key regulator of temperature-dependent morphogenesis
      is the molecular chaperone Hsp90, which has complex functional relationships with
      the transcription factor Hsf1. Although Hsf1 controls global transcriptional
      remodeling in response to heat shock, its impact on morphogenesis remains
      unknown. Here, we establish an intriguing paradigm whereby overexpression or
      depletion of C. albicans HSF1 induces morphogenesis in the absence of external
      cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation.
      HSF1 overexpression does not impact Hsp90 function, but rather induces a dose
      dependent expansion of Hsf1 direct targets that drives overexpression of positive
      regulators of filamentation, including Brg1 and Ume6, thereby bypassing the
      requirement for elevated temperature during morphogenesis. This work provides new
      insight into Hsf1-mediated environmentally contingent transcriptional control,
      implicates Hsf1 in regulation of a key virulence trait, and highlights
      fascinating biology whereby either overexpression or depletion of a single
      cellular regulator induces a profound developmental transition.

PMID- 29590107
TI  - Novel function of HATs and HDACs in homologous recombination through acetylation
      of human RAD52 at double-strand break sites.
AB  - The p300 and CBP histone acetyltransferases are recruited to DNA double-strand
      break (DSB) sites where they induce histone acetylation, thereby influencing the
      chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also
      acetylate non-histone proteins, and how their acetylation affects DSB repair,
      remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous
      recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated
      RAD52, we identified 13 potential acetylation sites in RAD52 by a mass
      spectrometry analysis. An immunofluorescence microscopy analysis revealed that
      RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated
      deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites,
      but dissociates prematurely from them. In the absence of RAD52 acetylation,
      RAD51, which plays a central role in HR, also dissociates prematurely from DSB
      sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia
      mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the
      acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase
      activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB
      sites. Our findings clarify the importance of RAD52 acetylation in HR and its
      underlying mechanism.

PMID- 29590108
TI  - Cross-species multiple environmental stress responses: An integrated approach to
      identify candidate genes for multiple stress tolerance in sorghum (Sorghum
      bicolor (L.) Moench) and related model species.
AB  - BACKGROUND: Crop response to the changing climate and unpredictable effects of
      global warming with adverse conditions such as drought stress has brought
      concerns about food security to the fore; crop yield loss is a major cause of
      concern in this regard. Identification of genes with multiple responses across
      environmental stresses is the genetic foundation that leads to crop adaptation to
      environmental perturbations. METHODS: In this paper, we introduce an integrated
      approach to assess candidate genes for multiple stress responses across-species.
      The approach combines ontology based semantic data integration with expression
      profiling, comparative genomics, phylogenomics, functional gene enrichment and
      gene enrichment network analysis to identify genes associated with plant stress
      phenotypes. Five different ontologies, viz., Gene Ontology (GO), Trait Ontology
      (TO), Plant Ontology (PO), Growth Ontology (GRO) and Environment Ontology (EO)
      were used to semantically integrate drought related information. RESULTS: Target
      genes linked to Quantitative Trait Loci (QTLs) controlling yield and stress
      tolerance in sorghum (Sorghum bicolor (L.) Moench) and closely related species
      were identified. Based on the enriched GO terms of the biological processes, 1116
      sorghum genes with potential responses to 5 different stresses, such as drought
      (18%), salt (32%), cold (20%), heat (8%) and oxidative stress (25%) were
      identified to be over-expressed. Out of 169 sorghum drought responsive QTLs
      associated genes that were identified based on expression datasets, 56% were
      shown to have multiple stress responses. On the other hand, out of 168 additional
      genes that have been evaluated for orthologous pairs, 90% were conserved across
      species for drought tolerance. Over 50% of identified maize and rice genes were
      responsive to drought and salt stresses and were co-located within
      multifunctional QTLs. Among the total identified multi-stress responsive genes,
      272 targets were shown to be co-localized within QTLs associated with different
      traits that are responsive to multiple stresses. Ontology mapping was used to
      validate the identified genes, while reconstruction of the phylogenetic tree was
      instrumental to infer the evolutionary relationship of the sorghum orthologs. The
      results also show specific genes responsible for various interrelated components
      of drought response mechanism such as drought tolerance, drought avoidance and
      drought escape. CONCLUSIONS: We submit that this approach is novel and to our
      knowledge, has not been used previously in any other research; it enables us to
      perform cross-species queries for genes that are likely to be associated with
      multiple stress tolerance, as a means to identify novel targets for engineering
      stress resistance in sorghum and possibly, in other crop species.

PMID- 29590109
TI  - Serum VEGF-A concentrations in patients with central nervous system (CNS) tumors.
AB  - Angiogenesis plays an essential role in tumors development. In case of central
      nervous system tumors, the most important role in this process plays VEGF-A. The
      purpose of this study was to determine the plasma concentration of this agent in
      patients treated surgically because of intracranial tumors. The study involved 48
      adult patients, both sexes, treated surgically because of a brain tumor. The
      control group consisted of 50 adult volunteers of both sexes, without cancer
      diagnosis. Based on the studies, it was found that serum VEGF-A levels before
      surgery are higher in patients with central nervous system tumors (10.39-150.57
      pg/ml, median 41.70 pg/ml) than in non-cancer patients (0.00-130.77 pg/ml, median
      22.56 pg/ml). The association between serum VEGF-A level and malignancy and
      histological type of intracranial tumor has not beed confirmed. The highest
      average preoperative serum VEGF-A level was found in patients with low grade
      gliomas, slightly lower (close to each other) in those with high grade gliomas
      and meningiomas, while the lowest level was characteristic for metastatic tumors.
      High variation in results was observed in patients with low grade gliomas (52.56
      pg/ml)-higher than those reported in patients with high grade gliomas (32.38
      pg/ml). In the rest types of tumors the differentiation was similar and
      oscillated within 23.08-27.50 pg/ml.

PMID- 29590111
TI  - An outer approximation method for the road network design problem.
AB  - Best investment in the road infrastructure or the network design is perceived as
      a fundamental and benchmark problem in transportation. Given a set of candidate
      road projects with associated costs, finding the best subset with respect to a
      limited budget is known as a bilevel Discrete Network Design Problem (DNDP) of NP
      hard computationally complexity. We engage with the complexity with a hybrid
      exact-heuristic methodology based on a two-stage relaxation as follows: (i) the
      bilevel feature is relaxed to a single-level problem by taking the network
      performance function of the upper level into the user equilibrium traffic
      assignment problem (UE-TAP) in the lower level as a constraint. It results in a
      mixed-integer nonlinear programming (MINLP) problem which is then solved using
      the Outer Approximation (OA) algorithm (ii) we further relax the multi-commodity
      UE-TAP to a single-commodity MILP problem, that is, the multiple OD pairs are
      aggregated to a single OD pair. This methodology has two main advantages: (i) the
      method is proven to be highly efficient to solve the DNDP for a large-sized
      network of Winnipeg, Canada. The results suggest that within a limited number of
      iterations (as termination criterion), global optimum solutions are quickly
      reached in most of the cases; otherwise, good solutions (close to global optimum
      solutions) are found in early iterations. Comparative analysis of the networks of
      Gao and Sioux-Falls shows that for such a non-exact method the global optimum
      solutions are found in fewer iterations than those found in some analytically
      exact algorithms in the literature. (ii) Integration of the objective function
      among the constraints provides a commensurate capability to tackle the multi
      objective (or multi-criteria) DNDP as well.

PMID- 29590110
TI  - Listening to a conversation with aggressive content expands the interpersonal
      space.
AB  - The distance individuals maintain between themselves and others can be defined as
      'interpersonal space'. This distance can be modulated both by situational factors
      and individual characteristics. Here we investigated the influence that the
      interpretation of other people interaction, in which one is not directly
      involved, may have on a person's interpersonal space. In the current study we
      measured, for the first time, whether the size of interpersonal space changes
      after listening to other people conversations with neutral or aggressive content.
      The results showed that the interpersonal space expands after listening to a
      conversation with aggressive content relative to a conversation with a neutral
      content. This finding suggests that participants tend to distance themselves from
      an aggressive confrontation even if they are not involved in it. These results
      are in line with the view of the interpersonal space as a safety zone surrounding
      one's body.

PMID- 29590112
TI  - Active BRAF-V600E is the key player in generation of a sessile serrated polyp
      specific DNA methylation profile.
AB  - BACKGROUND: Sessile serrated polyps (SSPs) have emerged as important precursors
      for a large number of sporadic colorectal cancers. They are difficult to detect
      during colonoscopy due to their flat shape and the excessive amounts of secreted
      mucin that cover the polyps. The underlying genetic and epigenetic basis for the
      emergence of SSPs is largely unknown with existing genetic studies confined to a
      limited number of oncogenes and tumor suppressors. A full characterization of the
      genetic and epigenetic landscape of SSPs would provide insight into their origin
      and potentially offer new biomarkers useful for detection of SSPs in stool
      samples. METHODS: We used a combination of genome-wide mutation detection, exome
      sequencing and DNA methylation profiling (via methyl-array and whole-genome
      bisulfite sequencing) to analyze multiple samples of sessile serrated polyps and
      compared these to familial adenomatous polyps. RESULTS: Our analysis revealed
      BRAF-V600E as the sole recurring somatic mutation in SSPs with no additional
      major genetic mutations detected. The occurrence of BRAF-V600E was coincident
      with a unique DNA methylation pattern revealing a set of DNA methylation markers
      showing significant (~3 to 30 fold) increase in their methylation levels,
      exclusively in SSP samples. These methylation patterns effectively distinguished
      sessile serrated polys from adenomatous polyps and did so more effectively than
      parallel gene expression profiles. CONCLUSIONS: This study provides an important
      example of a single oncogenic mutation leading to reproducible global DNA
      methylation changes. These methylated markers are specific to SSPs and could be
      of important clinical relevance for the early diagnosis of SSPs using non
      invasive approaches such as fecal DNA testing.

PMID- 29590113
TI  - The water relations and xylem attributes of albino redwood shoots (Sequioa
      sempervirens (D. Don.) Endl.).
AB  - Plants that lack chlorophyll are rare and typically restricted to holoparasites
      that obtain their carbon, water and mineral resources from a host plant. Although
      not parasites in the traditional sense, albino foliage, such as the sprouts that
      sometimes develop from redwood tree trunks, are comparable in function. They
      occur sporadically, and can reach the size of shrubs and in rare cases, trees.
      Albino redwoods are interesting because in addition to their reduced carbon
      resources, the absence of chloroplasts may impede proper stomatal function, and
      both aspects may have upstream consequences on water transport and xylem quality.
      We examined the water relations, water transport and xylem anatomical attributes
      of albino redwoods and show that similar to achlorophyllous and parasitic plants,
      albino redwoods have notably higher stomatal conductance than green sprouts.
      Given that stem xylem tracheid size as well as water transport efficiency are
      nearly equivalent in both albino and green individuals, we attribute the
      increased leaf water loss in albino sprouts to lower leaf to xylem area ratios,
      which favour improved hydration relative to green sprouts. The stems of albino
      redwoods were more vulnerable to drought-induced embolism than green stems, and
      this was consistent with the albino's weaker tracheids, as characterized by wall
      thickness to lumen diameter measures. Our results are both complementary and
      consistent with previous research on achlorophyllous plants, and suggest that the
      loss of stomatal control and photosynthetic capacity results in substantial
      vascular and anatomical adjustments.

PMID- 29590114
TI  - Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated
      with hearing loss in human and mouse.
AB  - Autosomal recessive nonsyndromic hearing loss is a genetically heterogeneous
      disorder. Here, we report a severe-to-profound sensorineural hearing loss locus,
      DFNB100 on chromosome 5q13.2-q23.2. Exome enrichment followed by massive parallel
      sequencing revealed a c.2510G>A transition variant in PPIP5K2 that segregated
      with DFNB100-associated hearing loss in two large apparently unrelated Pakistani
      families. PPIP5Ks enzymes interconvert 5-IP7 and IP8, two key members of the
      inositol pyrophosphate (PP-IP) cell-signaling family. Their actions at the
      interface of cell signaling and bioenergetic homeostasis can impact many
      biological processes. The c.2510G>A transition variant is predicted to substitute
      a highly invariant arginine residue with histidine (p.Arg837His) in the
      phosphatase domain of PPIP5K2. Biochemical studies revealed that the p.Arg837His
      variant reduces the phosphatase activity of PPIP5K2 and elevates its kinase
      activity. We found that in mouse inner ear, PPIP5K2 is expressed in the cochlear
      and vestibular sensory hair cells, supporting cells and spiral ganglion neurons.
      Mice homozygous for a targeted deletion of the Ppip5k2 phosphatase domain exhibit
      degeneration of cochlear outer hair cells and elevated hearing thresholds. Our
      demonstration that PPIP5K2 has a role in hearing in humans indicates that PP-IP
      signaling is important to hair cell maintenance and function within inner ear.

PMID- 29590115
TI  - Impaired neuronal maturation of hippocampal neural progenitor cells in mice
      lacking CRAF.
AB  - RAF kinases are major constituents of the mitogen activated signaling pathway,
      regulating cell proliferation, differentiation and cell survival of many cell
      types, including neurons. In mammals, the family of RAF proteins consists of
      three members, ARAF, BRAF, and CRAF. Ablation of CRAF kinase in inbred mouse
      strains causes major developmental defects during fetal growth and embryonic or
      perinatal lethality. Heterozygous germline mutations in CRAF result in Noonan
      syndrome, which is characterized by neurocognitive impairment that may involve
      hippocampal physiology. The role of CRAF signaling during hippocampal development
      and generation of new postnatal hippocampal granule neurons has not been examined
      and may provide novel insight into the cause of hippocampal dysfunction in Noonan
      syndrome. In this study, by crossing CRAF-deficiency to CD-1 outbred mice, a CRAF
      mouse model was established which enabled us to investigate the interplay of
      neural progenitor proliferation and postmitotic differentiation during adult
      neurogenesis in the hippocampus. Albeit the general morphology of the hippocampus
      was unchanged, CRAF-deficient mice displayed smaller granule cell layer (GCL)
      volume at postnatal day 30 (P30). In CRAF-deficient mice a substantial number of
      abnormal, chromophilic, fast dividing cells were found in the subgranular zone
      (SGZ) and hilus of the dentate gyrus (DG), indicating that CRAF signaling
      contributes to hippocampal neural progenitor proliferation. CRAF-deficient neural
      progenitor cells showed an increased cell death rate and reduced neuronal
      maturation. These results indicate that CRAF function affects postmitotic neural
      cell differentiation and points to a critical role of CRAF-dependent growth
      factor signaling pathway in the postmitotic development of adult-born neurons.

PMID- 29590117
TI  - A terrestrial vertebrate palaeontological review of Aldabra Atoll, Aldabra Group,
      Seychelles.
AB  - The Pleistocene vertebrate assemblage of Aldabra Atoll has been comparatively
      well studied. Three Upper Pleistocene fossil localities have been described
      yielding birds, reptiles and terrestrial molluscs. Those of Bassin Cabri and
      Bassin Lebine on Ile Picard are undated but must be in excess of 136,000 YBP,
      whereas Point Hodoul on Malabar Island is circa 100,000 YBP. Aldabra was
      seemingly completely submerged between deposition of the Ile Picard and Point
      Hodoul deposits, resulting in local faunal extinctions. Here we present the
      results of an ongoing study of fossil material collected on Ile Picard in 1987,
      which reveals a more diverse assemblage than previously realised. Notable
      discoveries are an Ardeola heron, three Procellariformes, tropic-bird Phaethon,
      gull Larus, rail Dryolimnas, harrier Circus and owl Tyto, plus evidence of
      recolonisation of the atoll by some seabirds, rail, harrier, owl, giant tortoises
      and lizards after the Ile Picard/Point Hodoul submergence event.

PMID- 29590116
TI  - Prospective evaluation of a rapid diagnostic test for Trypanosoma brucei
      gambiense infection developed using recombinant antigens.
AB  - BACKGROUND: Diagnosis and treatment are central elements of strategies to control
      Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Serological
      screening is a key entry point in diagnostic algorithms. The Card Agglutination
      Test for Trypanosomiasis (CATT) has been the most widely used screening test for
      decades, despite a number of practical limitations that were partially addressed
      by the introduction of rapid diagnostic tests (RDTs). However, current RDTs are
      manufactured using native antigens, which are challenging to produce.
      METHODOLOGY/PRINCIPAL FINDINGS: The objective of this study was to evaluate the
      accuracy of a new RDT developed using recombinant antigens (SD BIOLINE HAT 2.0),
      in comparison with an RDT produced using native antigens (SD BIOLINE HAT) and
      CATT. A total of 57,632 individuals were screened in the Democratic Republic of
      the Congo, either passively at 10 health centres, or actively by 5 mobile teams,
      and 260 HAT cases were confirmed by parasitology. The highest sensitivity was
      achieved with the SD BIOLINE HAT 2.0 (71.2%), followed by CATT (62.5%) and the SD
      BIOLINE HAT (59.0%). The most specific test was CATT (99.2%), while the
      specificity of the SD BIOLINE HAT and SD BIOLINE HAT 2.0 were 98.9% and 98.1%,
      respectively. Sensitivity of the tests was lower than previously reported, as
      they identified cases from partially overlapping sub-populations. All three tests
      were significantly more sensitive in passive than in active screening. Combining
      two or three tests resulted in a markedly increased sensitivity: When the SD
      BIOLINE HAT was combined with the SD BIOLINE HAT 2.0, sensitivity reached 98.4%
      in passive and 83.0% in active screening. CONCLUSIONS/SIGNIFICANCE: The
      recombinant antigen-based RDT was more sensitive than, and as specific as, the SD
      BIOLINE HAT. It was as sensitive as, but slightly less specific than CATT. While
      the practicality and cost-effectiveness of algorithms including several screening
      tests would need to be investigated, using two or more tests appears to enhance
      sensitivity of diagnostic algorithms, although some decrease in specificity is
      observed as well.

PMID- 29590118
TI  - Association between periconceptional weight loss and maternal and neonatal
      outcomes in obese infertile women.
AB  - BACKGROUND: Obesity in women of reproductive age has deleterious effects on
      reproductive and offspring health. In this study, we aimed to evaluate the
      association between the magnitude of periconceptional body-mass index (BMI)
      change and maternal and neonatal outcomes in obese infertile women who
      participated in the LIFEstyle study. The LIFEstyle study was a randomized
      controlled trial, evaluating if a six-month lifestyle intervention program prior
      to infertility treatment in obese infertile women improved birth rates, compared
      to prompt infertility treatment. METHODS AND FINDINGS: This is an exploratory
      post hoc analysis of the LIFEstyle study. We recorded periconceptional BMI change
      in women with an ongoing pregnancy, pooling data of all women, regardless of
      randomization arm. Periconceptional BMI change was calculated using weight at
      randomization and the periconceptional weight (measured in kilograms 12 weeks
      before or after conception and expressed as BMI change in units BMI (kg/m2)).
      Subsequently, women were categorized into quartiles according to the magnitude of
      their periconceptional change in BMI. The odds of maternal and neonatal outcomes
      were calculated using logistic regression analysis, comparing women in each of
      the first three weight change quartiles separately, and combined, to women in the
      fourth quartile. The fourth quartile was chosen as reference group, since these
      women had the least weight loss. We adjusted for periconceptional BMI,
      nulliparity and smoking status. In addition, we performed a subgroup analysis for
      singleton pregnancies. In the LIFEstyle study, 321 obese infertile women achieved
      an ongoing pregnancy which was conceived within 24 months after randomization.
      Periconceptional BMI change was available in 244 of these women (76%). Median BMI
      at randomization was 35.9 kg/m2. Women in the first quartile (Q1) had a
      periconceptional BMI change of <-2.1 kg/m2, women in the second quartile (Q2) 
      2.1 to -0.9 kg/m2, women in the third quartile (Q3) -0.9 to 0.1 kg/m2 and women
      in the fourth quartile (Q4) gained >=0.1 kg/m2. There were no significant
      differences between women in the quartiles regarding rates of excessive
      gestational weight gain (in term pregnancies), gestational diabetes, preterm
      birth, induction of labor, spontaneous vaginal birth and Caesarean section.
      Compared to women in Q4, the adjusted odds ratios, aOR, and 95% confidence
      interval for a hypertensive complication were; 0.55 (0.22-1.42) for women in Q1,
      0.30 (0.12-0.78) for women in Q2, 0.39 (0.16-0.96) for women in Q3 and 0.39 (0.19
      0.82) for women in Q1 to Q3 combined. In the subgroup analysis, investigating
      singleton pregnancies only, the statistically significant decreased rate of a
      hypertensive complication remained in women in Q2 (aOR 0.27, 95% CI 0.10-0.72)
      and Q3 (aOR 0.39, 95%CI 0.16-0.98) and when comparing women in Q1 to Q3 together
      to women in Q4 (aOR 0.38, 95%CI 0.18-0.80). Furthermore, there was a
      significantly decreased aOR (95%CI) of preterm birth in women in Q2 (0.24, 0.06
      0.98) and when combining women in Q1 to Q3 (0.37, 0.14-0.97) compared to women in
      Q4. CONCLUSIONS: These results suggest that a periconceptional decrease in BMI in
      obese infertile women could lead to a decrease of the rates of hypertensive
      pregnancy complications and preterm birth. The results are limited by the
      exploratory nature of the analyses and further evidence is necessary to provide
      more definitive conclusions.

PMID- 29590119
TI  - NF90/ILF3 is a transcription factor that promotes proliferation over
      differentiation by hierarchical regulation in K562 erythroleukemia cells.
AB  - NF90 and splice variant NF110 are DNA- and RNA-binding proteins encoded by the
      Interleukin enhancer-binding factor 3 (ILF3) gene that have been established to
      regulate RNA splicing, stabilization and export. The roles of NF90 and NF110 in
      regulating transcription as chromatin-interacting proteins have not been
      comprehensively characterized. Here, chromatin immunoprecipitation followed by
      deep sequencing (ChIP-seq) identified 9,081 genomic sites specifically occupied
      by NF90/NF110 in K562 cells. One third of NF90/NF110 peaks occurred at promoters
      of annotated genes. NF90/NF110 occupancy colocalized with chromatin marks
      associated with active promoters and strong enhancers. Comparison with 150 ENCODE
      ChIP-seq experiments revealed that NF90/NF110 clustered with transcription
      factors exhibiting preference for promoters over enhancers (POLR2A, MYC, YY1).
      Differential gene expression analysis following shRNA knockdown of NF90/NF110 in
      K562 cells revealed that NF90/NF110 activates transcription factors that drive
      growth and proliferation (EGR1, MYC), while attenuating differentiation along the
      erythroid lineage (KLF1). NF90/NF110 associates with chromatin to hierarchically
      regulate transcription factors that promote proliferation and suppress
      differentiation.

PMID- 29590120
TI  - The associations between water and sanitation and hookworm infection using cross
      sectional data from Togo's national deworming program.
AB  - BACKGROUND: Sustainable control of soil-transmitted helminths requires a
      combination of chemotherapy treatment and environmental interventions, including
      access to safe drinking water, sufficient water for hygiene, use of clean
      sanitation facilities, and handwashing (WASH). We quantified associations between
      home-, school-, and community-level WASH characteristics and hookworm infection
      both prevalence and eggs per gram of stool (intensity)-among Togolese school
      children in the context of community-based chemotherapy treatments administered
      in the country from 2010 through 2014. METHODOLOGY/PRINCIPAL FINDINGS: We
      analyzed data from two surveys conducted by the Togo Ministry of Health: a school
      based survey of students aged 6-9 years across Togo conducted in 2009 and a
      follow-up survey in 2015, after four to five years of preventive chemotherapy.
      Data were available for 16,473 students attending 1,129 schools in 2009 and for
      16,890 students from 1,126 schools in 2015. Between surveys, children in study
      schools received 0 to 8 rounds of deworming chemotherapy treatments. Few WASH
      conditions (only unimproved drinking water) were found to be significantly
      associated with the presence or absence of hookworms in an individual; however,
      quantitative eggs per gram of feces was associated with availability of
      unimproved drinking water, availability of improved drinking water either on or
      off school grounds, having a handwashing station with water available, and access
      to a sex-separate non-private or private latrine. The association between school
      WASH conditions and hookworm infection or burden often depended on the 2009
      prevalence of infection, as more WASH characteristics were found to be
      significant predictors of infection among schools with high underlying endemicity
      of hookworm. CONCLUSIONS/SIGNIFICANCE: Our findings emphasize the complex and
      often inconsistent or unpredictable relationship between WASH and hookworm.
      Specifically, we found that while preventive chemotherapy appeared to
      dramatically reduce hookworm infection, WASH was associated with infection
      intensity.

PMID- 29590121
TI  - A test of the symbol interdependency hypothesis with both concrete and abstract
      stimuli.
AB  - In Experiment 1, the symbol interdependency hypothesis was tested with both
      concrete and abstract stimuli. Symbolic (i.e., semantic neighbourhood distance)
      and embodied (i.e., iconicity) factors were manipulated in two tasks-one that
      tapped symbolic relations (i.e., semantic relatedness judgment) and another that
      tapped embodied relations (i.e., iconicity judgment). Results supported the
      symbol interdependency hypothesis in that the symbolic factor was recruited for
      the semantic relatedness task and the embodied factor was recruited for the
      iconicity task. Across tasks, and especially in the iconicity task, abstract
      stimuli resulted in shorter RTs. This finding was in contrast to the concreteness
      effect where concrete words result in shorter RTs. Experiment 2 followed up on
      this finding by replicating the iconicity task from Experiment 1 in an ERP
      paradigm. Behavioural results continued to show a reverse concreteness effect
      with shorter RTs for abstract stimuli. However, ERP results paralleled the N400
      and anterior N700 concreteness effects found in the literature, with more
      negative amplitudes for concrete stimuli.

PMID- 29590122
TI  - Association between six-minute walk distance and long-term outcomes in patients
      with pulmonary arterial hypertension: Data from the randomized SERAPHIN trial.
AB  - BACKGROUND: Patients with pulmonary arterial hypertension who achieve a six
      minute walk distance of 380-440 m may have improved prognosis. Using the
      randomized controlled trial of macitentan in pulmonary arterial hypertension
      (SERAPHIN), the association between six-minute walk distance and long-term
      outcomes was explored. METHODS: Patients with six-minute walk distance data at
      Month 6 were dichotomized as above or below the median six-minute walk distance
      (400 m) and assessed for future risk of pulmonary arterial hypertension-related
      death or hospitalization and all-cause death. Additionally, six-minute walk
      distance values at baseline, Month 6 and the change from baseline to Month 6 were
      categorized by quartiles. All associations were analyzed by the Kaplan-Meier
      method using a log-rank test and Cox regression models. RESULTS: Patients with a
      six-minute walk distance >400 m vs. <=400 m at Month 6 have a reduced risk of
      pulmonary arterial hypertension-related death or hospitalization (hazard ratio
      0.48; 95% confidence interval 0.33-0.69). The risk was also lower for patients
      with higher quartiles of six-minute walk distance at baseline or Month 6
      (baseline: hazard ratio [Q4 (>430 m) vs. Q1 (<=300 m)] 0.23; 95% confidence
      interval 0.15-0.36; Month 6: hazard ratio [Q4 (>455 m) vs. Q1 (<=348 m)] 0.33;
      95% confidence interval 0.19-0.55). In contrast, six-minute walk distance changes
      at Month 6 were not associated with the risk of pulmonary arterial hypertension
      related death or hospitalization (p = 0.477). These findings were consistent when
      adjusted for known confounders. Similar results were observed for the risk of all
      cause death up to end of study. CONCLUSIONS: Patients with pulmonary arterial
      hypertension walking >400 m had better long-term prognosis. Although changes in
      six-minute walk distance were not associated with long-term outcomes, assessing
      absolute six-minute walk distance values remains important in the clinical
      management of patients with pulmonary arterial hypertension.

PMID- 29590123
TI  - Ontogeny of juvenile freshwater pearl mussels, Margaritifera margaritifera
      (Bivalvia: Margaritiferidae).
AB  - The gills of juvenile freshwater bivalves undergo a complex morphogenesis that
      may correlate with changes in feeding ecology, but ontogenic studies on juvenile
      mussels are rare. Scanning electron microscopy was used to examine the
      ultrastructure and ontogeny of 117 juvenile freshwater pearl mussels
      (Margaritifera margaritifera) ranging in age from 1-44 months and length from
      0.49-8.90 mm. Three stages of gill development are described. In Stage 1 (5-9
      inner demibranch filaments), only unreflected inner demibranch filaments were
      present. In Stage 2 (9-17 inner demibranch filaments), inner demibranch filaments
      began to reflect when shell length exceeded 1.13 mm, at 13-16 months old.
      Reflection began in medial filaments and then proceeded anterior and posterior.
      In Stage 3 (28-94 inner demibranch filaments), outer demibranch filaments began
      developing at shell length > 3.1 mm and about 34 months of age. The oral groove
      on the inner demibranch was first observed in 34 month old specimens > 2.66 mm
      but was never observed on the outer demibranch. Shell length (R2 = 0.99) was a
      better predictor of developmental stage compared to age (R2 = 0.84). The full
      suite of gill ciliation was present on filaments in all stages. Interfilamentary
      distance averaged 31.3 MUm and did not change with age (4-44 months) or with size
      (0.75-8.9 mm). Distance between laterofrontal cirri couplets averaged 1.54 MUm
      and did not change significantly with size or age. Labial palp primordia were
      present in even the youngest individuals but ciliature became more diverse in
      more developed individuals. Information presented here is valuable to captive
      rearing programmes as it provides insight in to when juveniles may be
      particularly vulnerable to stressors due to specific ontogenic changes. The data
      are compared with two other recent studies of Margaritifera development.

PMID- 29590124
TI  - The Basel Face Database: A validated set of photographs reflecting systematic
      differences in Big Two and Big Five personality dimensions.
AB  - Upon a first encounter, individuals spontaneously associate faces with certain
      personality dimensions. Such first impressions can strongly impact judgments and
      decisions and may prove highly consequential. Researchers investigating the
      impact of facial information often rely on (a) real photographs that have been
      selected to vary on the dimension of interest, (b) morphed photographs, or (c)
      computer-generated faces (avatars). All three approaches have distinct
      advantages. Here we present the Basel Face Database, which combines these
      advantages. In particular, the Basel Face Database consists of real photographs
      that are subtly, but systematically manipulated to show variations in the
      perception of the Big Two and the Big Five personality dimensions. To this end,
      the information specific to each psychological dimension is isolated and modeled
      in new photographs. Two studies serve as systematic validation of the Basel Face
      Database. The Basel Face Database opens a new pathway for researchers across
      psychological disciplines to investigate effects of perceived personality.

PMID- 29590125
TI  - Automatic social comparison: Cognitive load facilitates an increase in negative
      thought accessibility after thin ideal exposure among women.
AB  - Women are routinely exposed to images of extremely slim female bodies (the thin
      ideal) in advertisements, even if they do not necessarily pay much attention to
      these images. We hypothesized that paradoxically, it is precisely in such
      conditions of low attention that the impact of the social comparison with the
      thin ideal might be the most pronounced. To test this prediction, one hundred and
      seventy-three young female participants were exposed to images of the thin ideal
      or of women's fashion accessories. They were allocated to either a condition of
      high (memorizing 10 digits) or low cognitive load (memorizing 4 digits). The main
      dependent measure was implicit: mean recognition latency of negative words,
      relative to neutral words, as assessed by a lexical decision task. The results
      showed that thin-ideal exposure did not affect negative word accessibility under
      low cognitive load but that it increased it under high cognitive load. These
      findings are consistent with the hypothesis that social comparison with the thin
      ideal is an automatic process, and contribute to explain why some strategies to
      prevent negative effects of thin-ideal exposure are inefficient.

PMID- 29590126
TI  - Risk of venous thromboembolism during rehabilitation of patients with spinal cord
      injury.
AB  - BACKGROUND: Patients with spinal cord injury (SCI) are at risk of thrombosis and
      bleeding. Data on the risks during rehabilitation are inconsistent, and
      thromboprophylactic strategies are heterogeneous. We aimed to evaluate the
      thrombotic risk and bleeding events of SCI patients during rehabilitation.
      METHODS: We retrospectively collected hospital record data of 263 consecutive SCI
      patients admitted at a rehabilitation clinic. 78 patients with acute venous
      thromboembolism (VTE) at the primary center, without acute trauma or lower
      extremity paresis, less than one month rehabilitation, or reasons for long-term
      therapeutic anticoagulation, were excluded. All patients received pharmacologic
      thromboprophylaxis throughout rehabilitation. Primary endpoint was objectively
      diagnosed VTE; secondary endpoint was bleeding. RESULTS: Of 185 patients, 162
      (88%) were men; mean age was 47.8 years. 94 patients were tetraplegic, 91
      paraplegic. During a mean (+/-SD) time of 5.1+/-2.1 months, VTE was diagnosed in
      8 patients. After excluding five patients with VTE detected within 2 days after
      admission, the probability of developing VTE after 6 months of rehabilitation was
      2% (95% CI 0-4.4%). Only high D-Dimer upon admission was associated with risk of
      VTE (adjusted HR 2.3, 95% CI 1.4-4.1). Of 24 bleedings, 14 (64%) occurred at the
      heparin injection site. Two patients had major bleeding and five had clinically
      relevant non major bleeding. CONCLUSION: SCI patients are at risk of VTE and
      bleeding during rehabilitation. Strategies need to be developed to identify these
      patients in order to initiate adequate anticoagulation. Direct oral
      anticoagulants, which have a favourable risk-benefit profile and are convenient,
      should be explored.

PMID- 29590127
TI  - Mimicking and anticipating others' actions is linked to Social Information
      Processing.
AB  - It is widely known that individuals frequently imitate each other in social
      situations and that such mimicry fulfills an important social role in the sense
      that it functions as a social glue. With reference to the anticipated action
      effect, it has recently been demonstrated that individuals do not only imitate
      others, but also engage in anticipated action before the observed person starts
      engaging in that action. Interestingly, both phenomena (i.e., mimicry and
      anticipated action) rely on tracking others' social behavior. Therefore, in the
      present research we investigated whether mimicry and anticipated action are
      related to social abilities as indicated by measures of social intelligence. The
      results demonstrate for the first time that mimicry as well as anticipated action
      is correlated with an important aspect of social intelligence-namely the ability
      to process social information. Theoretical implications and limitations are
      discussed.

PMID- 29590128
TI  - Osthole inhibits gastric cancer cell proliferation through regulation of
      PI3K/AKT.
AB  - Osthole is an active compound isolated from Chinese herb Cnidium monnieri (L.)
      Cusson, and had been reported to possess antitumor effect. However, the effect of
      osthole on the gastric cancer cells has not been investigated. In this study, the
      effects of osthole on the proliferation of human gastric cancer cells were
      tested. The data showed that osthole treatment significantly inhibited the
      proliferation of gastric cancer cells and resulted in the cell cycle arrest at
      G2/M phase in a dose-dependent manner. Western-blot study showed that the
      expression of cyclin B1 and cdc2 was markedly reduced by osthole. Moreover,
      expression of PI3K and pAKT was also significantly suppressed, and the results
      indicated that the inhibition of pAKT, cyclin B1, and cdc2 levels by osthole was
      notably enhanced by a PI3K inhibitor. These results demonstrate that osthole
      could inhibit gastric cancer cells proliferation via induction of cell cycle
      arrest at G2/M phase by the reduction of PI3K/AKT.

PMID- 29590129
TI  - Humanin (HN) and glucose transporter 8 (GLUT8) in pregnancies complicated by
      intrauterine growth restriction.
AB  - BACKGROUND: Intrauterine growth restriction (IUGR) results from a lack of
      nutrients transferred to the developing fetus, particularly oxygen and glucose.
      Increased expression of the cytoprotective mitochondrial peptide, humanin (HN),
      and the glucose transporter 8, GLUT8, has been reported under conditions of
      hypoxic stress. However, the presence and cellular localization of HN and GLUT8
      in IUGR-related placental pathology remain unexplored. Thus, we undertook this
      study to investigate placental expression of HN and GLUT8 in IUGR-affected versus
      normal pregnancies. RESULTS: We found 1) increased HN expression in human IUGR
      affected pregnancies on the maternal aspect of the placenta (extravillous
      trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for
      gestational age) pregnancies, and a concomitant increase in GLUT8 expression in
      the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co
      immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated
      hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but
      attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells.
      CONCLUSIONS: There was elevated HN expression with cytoplasmic localization to
      EVTs on the maternal aspect of the human placenta affected by IUGR, also
      associated with increased GLUT8 expression. We found that while hypoxia increased
      both HN and GLUT8, serum deprivation increased HN expression alone. Also, a
      protein-protein interaction between HN and GLUT8 suggests that their interaction
      may fulfill a biologic role that requires interdependency. Future investigations
      delineating molecular interactions between these proteins are required to fully
      uncover their role in IUGR-affected pregnancies.

PMID- 29590130
TI  - Private sector tuberculosis prevention in the US: Characteristics associated with
      interferon-gamma release assay or tuberculin skin testing.
AB  - OBJECTIVE: To determine whether latent tuberculosis infection risk factors are
      associated with an increased likelihood of latent tuberculosis infection testing
      in the US private healthcare sector. DATA SOURCE: A national sample of medical
      and pharmacy claims representing services rendered January 2011 through December
      2013 for 3,997,986 commercially insured individuals in the US who were 0 to 64
      years of age. STUDY DESIGN: We used multivariable logistic regression models to
      determine whether TB/LTBI risk factors were associated with an increased
      likelihood of Interferon-Gamma Release Assay (IGRA) or Tuberculin Skin Test (TST)
      testing in the private sector. PRINCIPAL FINDINGS: 4.31% (4.27-4.34%) received at
      least one TST/IGRA test between 2011 and 2013 while 1.69% (1.67-1.72%) received a
      TST/IGRA test in 2013. Clinical risk factors associated with a significantly
      increased likelihood of testing included HIV, immunosuppressive therapy, exposure
      to tuberculosis, a history of tuberculosis, diabetes, tobacco use, end stage
      renal disease, and alcohol use disorder. Other significant variables included
      gender, age, asthma, the state tuberculosis rate, population density, and percent
      of foreign-born persons in a county. CONCLUSIONS: Private sector TST/IGRA testing
      is not uncommon and testing varies with clinical risk indicators. Thus, the
      private sector can be a powerful resource in the fight against tuberculosis.
      Analyses of administrative data can inform how best to leverage private sector
      healthcare toward tuberculosis prevention activities.

PMID- 29590131
TI  - Peer-to-peer lending and bias in crowd decision-making.
AB  - Peer-to-peer lending is hypothesized to help equalize economic opportunities for
      the world's poor. We empirically investigate the "flat-world" hypothesis, the
      idea that globalization eventually leads to economic equality, using
      crowdfinancing data for over 660,000 loans in 220 nations and territories made
      between 2005 and 2013. Contrary to the flat-world hypothesis, we find that peer
      to-peer lending networks are moving away from flatness. Furthermore, decreasing
      flatness is strongly associated with multiple variables: relatively stable
      patterns in the difference in the per capita GDP between borrowing and lending
      nations, ongoing migration flows from borrowing to lending nations worldwide, and
      the existence of a tie as a historic colonial. Our regression analysis also
      indicates a spatial preference in lending for geographically proximal borrowers.
      To estimate the robustness for these patterns for future changes, we construct a
      network of borrower and lending nations based on the observed data. Then, to
      perturb the network, we stochastically simulate policy and event shocks (e.g.,
      erecting walls) or regulatory shocks (e.g., Brexit). The simulations project a
      drift towards rather than away from flatness. However, levels of flatness persist
      only for randomly distributed shocks. By contrast, loss of the top borrowing
      nations produces more flatness, not less, indicating how the welfare of the
      overall system is tied to a few distinctive and critical country-pair
      relationships.

PMID- 29590133
TI  - The effect of pond dyes on oviposition and survival in wild UK Culex mosquitoes.
AB  - British Culex pipiens complex [Culex pipiens sensu lato) mosquito distribution,
      abundance, and potential for disease transmission are intimately linked to their
      environment. Pond and lake dyes that block light to restrict algal photosynthesis
      are a relatively new product assumed to be an environmentally friendly since they
      are based on food dyes. Their use in urban garden ponds raises questions linked
      to mosquito oviposition, since coloured water can be an attractant. Culex (mostly
      pipiens) is commonly found in UK gardens and is a potential vector of viruses
      including the West Nile Virus (WNV). Any factors that significantly change the
      distribution and population of Cx pipiens could impact future risks of disease
      transmission. A gravid trap was used to catch female Cx pipiens mosquitoes for
      use in oviposition choice tests in laboratory and semi-field conditions. Two
      types of pond dye, blue and shadow (which looks slightly red), were tested for
      their impact on oviposition and survival of wild caught Cx pipiens. There were no
      significant differences in the number of egg batches laid when gravid mosquitoes
      were given a choice between either blue dye and clear water or shadow dye and
      clear water indicating that these dyes are not attractants. Larvae hatched from
      egg batches laid by wild-caught gravid females were used to measure survival to
      adulthood with or without dye, in a habitat controlled to prevent further
      colonisation. The experiment was run twice, once in the summer and again in the
      autumn, whereas the dyes had no impact on emergence in the summer, there were
      highly significant reductions in emergence of adults in both dye treated habitats
      in the autumn. Containers with or without shadow dye were placed outside to
      colonise naturally and were sampled weekly for larvae and pupae over a 6 month
      period through summer and autumn. There was a significant negative effect of
      shadow dye on pupal abundance in a three week period over the summer, but
      otherwise there was no effect. It is likely that population abundance and food
      was a more powerful factor for mosquito survival than the dye.

PMID- 29590132
TI  - GLP-1 receptor agonist ameliorates obesity-induced chronic kidney injury via
      restoring renal metabolism homeostasis.
AB  - Increasing evidence indicates that obesity is highly associated with chronic
      kidney disease (CKD). GLP-1 receptor (GLP-1R) agonist has shown benefits on
      kidney diseases, but its direct role on kidney metabolism in obesity is still not
      clear. This study aims to investigate the protection and metabolic modulation
      role of liraglutide (Lira) on kidney of obesity. Rats were induced obese by high
      fat diet (HFD), and renal function and metabolism changes were evaluated by
      metabolomic, biological and histological methods. HFD rats exhibited systemic
      metabolic disorders such as obesity, hyperlipidemia and impaired glucose
      tolerance, as well as renal histological and function damages, while Lira
      significantly ameliorated these adverse effects in HFD rats. Metabolomic data
      showed that Lira directly reduced renal lipids including fatty acid residues,
      cholesterol, phospholipids and triglycerides, and improved mitochondria
      metabolites such as succinate, citrate, taurine, fumarate and nicotinamide
      adenine dinucleotide (NAD+) in the kidney of HFD rats. Furthermore, we revealed
      that Lira inhibited renal lipid accumulation by coordinating lipogenic and
      lipolytic signals, and partly rescued renal mitochondria function via
      Sirt1/AMPK/PGC1alpha pathways in HFD rats. This study suggested that Lira
      alleviated HFD-induced kidney injury at least partly via directly restoring renal
      metabolism, thus GLP-1R agonist is a promising therapy for obesity-associated
      CKD.

PMID- 29590134
TI  - Patient preferences for Interferon-beta in Iran: A discrete choice experiment.
AB  - Multiple sclerosis is a chronic, progressive, and common disease affecting the
      central nervous system in young adults. Interferon-beta is one of the most widely
      used medicines to reduce the disease progression. Given the variety of drugs in
      this category, we aimed to identify the preferences of patients for IFN-beta that
      play an important role in policymaking in this area. Discrete choice experiment
      method was used in the present study to identify and prioritize those attributes
      that are of interest to MS patients and increases the utility of the use of IFN
      beta in their treatment. Questionnaires were given to 358 patients in Isfahan
      Iran, who were asked to choose between the two treatment choices in each
      scenario. The results of the logit model showed that the changes in the efficacy
      lead to the most changes in the patient utility. Changes in side effects and ease
      of injection have been placed in the next rankings. Considering the drug
      attributes considered more desirable by patients can lead to greater medication
      adherence and possibly better treatment outcomes. Also, pharmaceutical companies,
      the health ministry, the Food and Drug Administration, insurance organizations,
      and neurologists can benefit from this information in production and importation,
      policymaking, and prescription.

PMID- 29590135
TI  - A myeloperoxidase precursor, pro-myeloperoxidase, is present in human plasma and
      elevated in cardiovascular disease patients.
AB  - Myeloperoxidase (MPO)-derived oxidants have emerged as a key contributor to
      tissue damage in inflammatory conditions such as cardiovascular disease. Pro
      myeloperoxidase (pro-MPO), an enzymatically active precursor of myeloperoxidase
      (MPO), is known to be secreted from cultured bone marrow and promyelocytic
      leukemia cells, but evidence for the presence of pro-MPO in circulation is
      lacking. In the present study, we used a LC-MS/MS in addition to immunoblot
      analyses to show that pro-MPO is present in human blood plasma. Furthermore, we
      found that pro-MPO was more frequently detected in plasma from patients with
      myocardial infarction compared to plasma from control donors. Our study suggests
      that in addition to mature MPO, circulating pro-MPO may cause oxidative
      modifications of proteins thereby contributing to cardiovascular disease.

PMID- 29590136
TI  - Alveolar leak develops by a rich-get-richer process in ventilator-induced lung
      injury.
AB  - Acute respiratory distress syndrome (ARDS) is a life-threatening condition for
      which there are currently no medical therapies other than supportive care
      involving the application of mechanical ventilation. However, mechanical
      ventilation itself can worsen ARDS by damaging the alveolocapillary barrier in
      the lungs. This allows plasma-derived fluid and proteins to leak into the
      airspaces of the lung where they interfere with the functioning of pulmonary
      surfactant, which increases the stresses of mechanical ventilation and worsens
      lung injury. Once such ventilator-induced lung injury (VILI) is underway,
      managing ARDS and saving the patient becomes increasingly problematic.
      Maintaining an intact alveolar barrier thus represents a crucial management goal,
      but the biophysical processes that perforate this barrier remain incompletely
      understood. To study the dynamics of barrier perforation, we subjected initially
      normal mice to an injurious ventilation regimen that imposed both volutrauma
      (overdistension injury) and atelectrauma (injury from repetitive reopening of
      closed airspaces) on the lung, and observed the rate at which macromolecules of
      various sizes leaked into the airspaces as a function of the degree of overall
      injury. Computational modeling applied to our findings suggests that perforations
      in the alveolocapillary barrier appear and progress according to a rich-get
      richer mechanism in which the likelihood of a perforation getting larger
      increases with the size of the perforation. We suggest that atelectrauma causes
      the perforations after which volutrauma expands them. This mechanism explains why
      atelectrauma appears to be essential to the initiation of VILI in a normal lung,
      and why atelectrauma and volutrauma then act synergistically once VILI is
      underway.

PMID- 29590137
TI  - Linking hard and soft traits: Physiology, morphology and anatomy interact to
      determine habitat affinities to soil water availability in herbaceous dicots.
AB  - BACKGROUND AND AIMS: Species' habitat affinities along environmental gradients
      should be determined by a combination of physiological (hard) and morpho
      anatomical (soft) traits. Using a gradient of soil water availability, we address
      three questions: How well can we predict habitat affinities from hard traits,
      from soft traits, and from a combination of the two? How well can we predict
      species' physiological responses to drought (hard traits) from their soft traits?
      Can we model a causal sequence as soft traits -> hard traits -> species
      distributions? METHODS: We chose 25 species of herbaceous dicots whose affinities
      for soil moisture have already been linked to 5 physiological traits (stomatal
      conductance and net photosynthesis measured at soil field capacity, water use
      efficiency, stomatal conductance and soil water potential measured when leaves
      begin to wilt). Under controlled conditions in soils at field capacity, we
      measured five soft traits (leaf dry matter content, specific leaf area, leaf
      nitrogen content, stomatal area, specific root length). KEY RESULTS: Soft traits
      alone were poor predictors (R2 = 0.129) while hard traits explained 48% of
      species habitat affinities. Moreover, hard traits were significantly related to
      combinations of soft traits. From a priori biological knowledge and hypothesized
      ecological links we built a path model showing a sequential pattern soft traits 
      > hard traits -> species distributions and accounting for 59.6% (p = 0.782) of
      habitat wetness. CONCLUSIONS: Both direct and indirect causal relationships
      existed between soft traits, hard traits and species' habitat preferences. The
      poor predictive abilities of soft traits alone were due to the existence of
      antagonistic and synergistic direct and indirect effects of soft traits on
      habitat preferences mediated by the hard traits. To obtain a more realistic model
      applicable to a population level, it has to be tested in an experiment including
      species competition for water supply.

PMID- 29590138
TI  - Effect of multiple drug resistance on total medical costs among patients with
      intra-abdominal infections in China.
AB  - BACKGROUND: Multiple drug resistant (MDR) intra-abdominal infections (IAIs) are
      associated with notable direct and societal costs. As previous studies have not
      considered the impact of MDR on the total medical costs (TMCs) of IAIs, the
      present one examines this, as well as further estimates the additional costs at a
      national level. METHODS: This is a retrospective study. Firstly, we randomly
      selected a sample of 40% of all inpatients discharged between 2014 and 2015 from
      a teaching hospital, due to limits in budget and the large number of patients.
      Then, we manually selected 254 patients with IAIs according to the International
      Classification of Disease, 10th revision, using electronic medical records.
      Eventually, 101 patients with IAIs (64 MDR patients and 37 non-MDR patients) were
      included after excluding cases without laboratory test results, any pathogens
      detected, or antimicrobial resistant pathogens. Univariate analysis and a
      generalized linear model were applied to assess the parameters associated with
      TMCs. RESULTS: Compared to non-MDR patients, those with MDR pathogens were
      significantly associated with higher TMCs, higher antimicrobial costs, higher
      antimicrobial usage, larger number of pathogens, and longer length of stay and
      were more likely to have insurance and combination antimicrobial therapy. In
      addition, the average TMC among patients with MDR pathogens was Y 131801, which
      is Y 90201 higher than those without MDR pathogens. If our results are applied to
      the whole country, the sum of all attributable TMCs was Y 37 billion. The
      societal costs, furthermore, were Y111 billion in 2015. CONCLUSION: Our results
      provide information that should lead to increased efforts to reduce inappropriate
      antimicrobial therapy, in order to decrease the emergence of MDR pathogens and to
      reduce their economic burden.

PMID- 29590139
TI  - The effects of unilateral and bilateral eccentric overload training on
      hypertrophy, muscle power and COD performance, and its determinants, in team
      sport players.
AB  - The study aimed to compare the chronic eccentric-overload training effects of
      unilateral (lateral lunge) vs bilateral (half-squat) using an inertial device, on
      hypertrophy and physical performance. Twenty-seven young team sports male players
      performed a 4 sets of 7 repetitions of inertial eccentric overload training,
      biweekly for 6 weeks, distributed in unilateral lunge group (UG: age: 22.8 +/-
      2.9 years; body mass: 75.3 +/- 8.8 kg; height: 177.3 +/- 3.7 cm) and bilateral
      squat group (BG: age: 22.6 +/- 2.7 years; body mass: 79.5 +/- 12.8 kg; height:
      164.2 +/- 7 cm). Lower limb muscle volume, counter movement jump (CMJ), power
      with both (POWER), dominant (POWERd) and no-dominant leg (POWERnd), change of
      direction turn of 90 degrees  with dominant (COD90d) and no-dominant leg
      (COD90nd) and 180 degrees  (COD180d and COD180nd), and 10m sprint time (T-10m)
      were measured pre and post-intervention. The UG obtained an increase of adductor
      major (+11.1%) and vastus medialis (+12.6%) higher than BG. The BG obtained an
      increase of vastus lateralis (+9.9%) and lateral gastrocnemius (+9.1%) higher
      than UG. Both groups improved CMJ, POWER, POWERd, POWERnd, COD90 and DEC-COD90,
      without changes in T-10m. The UG decrease DEC-COD90nd (-21.1%) and BG increase
      POWER (+38.6%) substantially more than the other group. Six-weeks of unilateral /
      bilateral EO training induce substantial improvements in lower limbs muscle
      volume and functional performance, although unilateral training seems to be more
      effective in improving COD90 performance.

PMID- 29590140
TI  - Understanding the effects of predictability, duration, and spatial pattern of
      drying on benthic invertebrate assemblages in two contrasting intermittent
      streams.
AB  - In the present study, we examined the effects of different drying conditions on
      the composition, structure and function of benthic invertebrate assemblages. We
      approached this objective by comparing invertebrate assemblages in perennial and
      intermittent sites along two intermittent Mediterranean streams with contrasting
      predictability, duration, and spatial patterns of drying: Fuirosos (high
      predictability, short duration, downstream drying pattern) and Rogativa (low
      predictability, long duration, patchy drying pattern). Specifically, we
      quantified the contribution of individual taxa to those differences, the degree
      of nestedness, and shifts in the composition, structure and function of benthic
      invertebrate assemblages along flow intermittence gradients. We observed greater
      effects of drying on the benthic invertebrate composition in Fuirosos than in
      Rogativa, resulting in a higher dissimilarity of assemblages between perennial
      and intermittent sites, as well as a lower degree of nestedness. Furthermore, a
      higher number of biotic metrics related to richness, abundance and biological
      traits were significantly different between perennial and intermittent sites in
      Fuirosos, despite a shorter dry period compared to Rogativa. At the same time,
      slightly different responses were detected during post-drying (autumn) than pre
      drying (spring) conditions in this stream. In Rogativa, shifts in benthic
      invertebrate assemblages along increasing gradients of flow intermittence were
      found for three metrics (Ephemeroptera, Plecoptera and Trichoptera (EPT) and
      Odonata, Coleoptera and Heteroptera (OCH) abundances and aerial active dispersal.
      Furthermore, we demonstrated that combined gradients of dry period duration and
      distance to nearest perennial reach can generate complex, and different,
      responses of benthic invertebrate assemblages, depending on the flow
      intermittence metric. Our study advances the notion that special attention should
      be paid to the predictability, duration and spatial patterns of drying in
      intermittent streams in order to disentangle the effects of drying on benthic
      invertebrate assemblages, in particular in areas subject to high spatial
      heterogeneity and temporal variability in drying conditions.

PMID- 29590141
TI  - Length of hospitalization and mortality for bleeding during treatment with
      warfarin, dabigatran, or rivaroxaban.
AB  - BACKGROUND: Different outcomes among patients hospitalized for bleeding after
      starting anticoagulation could influence choice of anticoagulant. We compared
      length of hospitalization, proportion of Intensive Care Unit (ICU) admissions,
      ICU length of stay, and 30- and 90-day mortality for adults with atrial
      fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or
      rivaroxaban. METHODS: An US commercial database of 38 million members from 1
      November 2010 to 31 March 2014 was used to examine adults with atrial
      fibrillation hospitalized for bleeding after starting warfarin (2,446),
      dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean
      total length of hospitalization, proportion of ICU admissions, mean length of ICU
      stay, and all-cause 30- and 90-day mortality. RESULTS: Warfarin users were older
      and had more comorbidities. Multivariable regression modeling with propensity
      score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI
      1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p
      < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days
      longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no
      differences in the proportion of ICU admissions. Among ICU admissions, warfarin
      users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users
      and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was
      no difference in ICU stay between dabigatran and rivaroxaban users. There were no
      differences in 30- and 90-day all-cause mortality. CONCLUSIONS: Rivaroxaban and
      dabigatran were associated with shorter hospitalizations; however, there were no
      differences in 30- and 90-day mortality. These findings suggest bleeding
      associated with the newer agents is not more dangerous than bleeding associated
      with warfarin.

PMID- 29590142
TI  - Sunscreen use optimized by two consecutive applications.
AB  - Sunscreen users are often inadequately protected and become sunburned. This study
      aimed to investigate how much two consecutive sunscreen applications increased
      the quantity of sunscreen applied and decreased the skin area left without
      sunscreen (missed area) compared to a single application. Thirty-one healthy
      volunteers wearing swimwear were included and applied sunscreen two consecutive
      times in a laboratory environment. Participants had pictures taken in black light
      before and after each application. As sunscreens absorb black light, the darkness
      of the skin increased with increasing amounts of sunscreen applied. We conducted
      a standard curve establishing a link between change in picture darkness and
      quantity of sunscreen. The quantity of sunscreen at selected skin sites as well
      as the percentage of missed area was determined after each application.
      Participants had missed a median of 20% of their available body surface after a
      single application. After double application they had missed 9%. The decrease in
      missed areas was significant for the whole body surface and for each of the body
      regions separately. The median participant had applied between 13% and 100% more
      sunscreen at the selected skin sites after double application than after single
      application. We recommend double application, especially before intense sun
      exposure.

PMID- 29590143
TI  - Short term evaluation of respiratory effort by premature infants supported with
      bubble nasal continuous airway pressure using Seattle-PAP and a standard bubble
      device.
AB  - BACKGROUND: Almost one million prematurely born infants die annually from
      respiratory insufficiency, predominantly in countries with limited access to
      respiratory support for neonates. The primary hypothesis tested in the present
      study was that a modified device for bubble nasal continuous positive airway
      pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated
      by esophageal pressure-rate products. METHODS: Infants born <32 weeks gestation
      and stable on Bn-CPAP with FiO2 <0.30 were studied within 72 h following
      delivery. Esophageal pressures during spontaneous breathing were measured during
      2 h on standard Bn-CPAP, then 2 h with Bn-CPAP using a modified bubble device
      presently termed Seattle-PAP, which produces a different pattern of pressure
      fluctuations and which provided greater respiratory support in preclinical
      studies, then 2 h on standard Bn-CPAP. RESULTS: All 40 infants enrolled completed
      the study and follow-up through 36 wks post menstrual age or hospital discharge,
      whichever came first. No infants were on supplemental oxygen at completion of
      follow-up. No infants developed pneumothoraces or nasal trauma, and no adverse
      events attributed to the study were observed. Pressure-rate products on the two
      devices were not different, but effort of breathing, assessed by areas under
      esophageal pressure-time curves, was lower with Seattle-PAP than with standard Bn
      CPAP. CONCLUSION: Use of Seattle-PAP to implement Bn-CPAP lowers the effort of
      breathing exerted even by relatively healthy spontaneously breathing premature
      neonates. Whether the lower effort of breathing observed with Seattle-PAP
      translates to improvements in neonatal mortality or morbidity will need to be
      determined by studies in appropriate patient populations.

PMID- 29590144
TI  - Administration of growth factors promotes salisphere formation from irradiated
      parotid salivary glands.
AB  - Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and
      the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy
      is to target the tumor, secondary exposure occurs in surrounding normal tissues,
      such as the salivary glands. As a result, despite successful treatment of the
      cancer, patients are left with long-term side effects due to direct damage to the
      salivary glands. The effect is chronic and currently there is no treatment. Stem
      cells are an attractive therapeutic option for treatment of radiation-induced
      glandular dysfunction because of the potential to regenerate damaged cell
      populations and restore salivary gland function. However, limited knowledge about
      the endogenous stem cell population post irradiation hinders the development for
      stem cell-based therapies. In this study, an ex vivo sphere formation cell
      culture system was utilized to assess the self-renewal capacity of cells derived
      from parotid salivary glands at a chronic time point following radiation.
      Salivary glands from irradiated mice generate significantly fewer salispheres,
      but can be stimulated with fetal bovine serum (FBS) to generate an equivalent
      number of salispheres as unirradiated salivary glands. Interestingly, the number
      and size of salispheres formed is dependent on the concentration of FBS
      supplemented into the media. Salispheres derived from irradiated glands and
      cultured in FBS media were found to contain cells that proliferate and express
      progenitor and acinar cell markers such as Keratin 5, Keratin 14, Aquaporin 5,
      and NKCC1. Utilization of insulin-like growth factor (IGF1) injections following
      radiation treatment restores salivary gland function and improves salisphere
      generation. These findings indicate that stimulation of these cellular
      populations may provide a promising avenue for the development of cell-based
      therapies for radiation-induced salivary gland damage.

PMID- 29590145
TI  - Genomic profiling of bovine corpus luteum maturation.
AB  - To unveil novel global changes associated with corpus luteum (CL) maturation, we
      analyzed transcriptome data for the bovine CL on days 4 and 11, representing the
      developing vs. mature gland. Our analyses revealed 681 differentially expressed
      genes (363 and 318 on day 4 and 11, respectively), with >=2 fold change and FDR
      of <5%. Different gene ontology (GO) categories were represented prominently in
      transcriptome data at these stages (e.g. days 4: cell cycle, chromosome, DNA
      metabolic process and replication and on day 11: immune response; lipid metabolic
      process and complement activation). Based on bioinformatic analyses, select genes
      expression in day 4 and 11 CL was validated with quantitative real-time PCR. Cell
      specific expression was also determined in enriched luteal endothelial and
      steroidogenic cells. Genes related to the angiogenic process such as NOS3, which
      maintains dilated vessels and MMP9, matrix degrading enzyme, were higher on day
      4. Importantly, our data suggests day 11 CL acquire mechanisms to prevent blood
      vessel sprouting and promote their maturation by expressing NOTCH4 and JAG1,
      greatly enriched in luteal endothelial cells. Another endothelial specific gene,
      CD300LG, was identified here in the CL for the first time. CD300LG is an adhesion
      molecule enabling lymphocyte migration, its higher levels at mid cycle are
      expected to support the transmigration of immune cells into the CL at this stage.
      Together with steroidogenic genes, most of the genes regulating de-novo
      cholesterol biosynthetic pathway (e.g HMGCS, HMGCR) and cholesterol uptake from
      plasma (LDLR, APOD and APOE) were upregulated in the mature CL. These findings
      provide new insight of the processes involved in CL maturation including blood
      vessel growth and stabilization, leucocyte transmigration as well as progesterone
      synthesis as the CL matures.

PMID- 29590146
TI  - The impact of pharmacists-led medicines reconciliation on healthcare outcomes in
      secondary care: A systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Adverse drug events (ADEs) impose a major clinical and cost burden on
      acute hospital services. It has been reported that medicines reconciliation
      provided by pharmacists is effective in minimizing the chances of hospital
      admissions related to adverse drug events. OBJECTIVE: To update the previous
      assessment of pharmacist-led medication reconciliation by restricting the review
      to randomized controlled trials (RCTs) only. METHODS: Six major online databases
      were sifted up to 30 December 2016, without inception date (Embase, Medline Ovid,
      PubMed, BioMed Central, Web of Science and Scopus) to assess the effect of
      pharmacist-led interventions on medication discrepancies, preventable adverse
      drug events, potential adverse drug events and healthcare utilization. The
      Cochrane tool was applied to evaluate the chances of bias. Meta-analysis was
      carried out using a random effects model. RESULTS: From 720 articles identified
      on initial searching, 18 RCTs (6,038 patients) were included. The quality of the
      included studies was variable. Pharmacists-led interventions led to an important
      decrease in favour of the intervention group, with a pooled risk ratio of 42% RR
      0.58 (95% CI 0.49 to 0.67) P<0.00001 in medication discrepancy. Reductions in
      healthcare utilization by 22% RR 0.78 (95% CI 0.61 to 1.00) P = 0.05, potential
      ADEs by10% RR 0.90 (95% CI 0.78 to 1.03) P = 0.65 and preventable ADEs by 27% RR
      0.73 (0.22 to 2.40) P = 0.60 were not considerable. CONCLUSION: Pharmacists-led
      interventions were effective in reducing medication discrepancies. However, these
      interventions did not lead to a significant reduction in potential and
      preventable ADEs and healthcare utilization.

PMID- 29590147
TI  - Influence of bone-conducted vibration on simulator sickness in virtual reality.
AB  - Use of virtual reality (VR) technology is often accompanied by a series of
      unwanted symptoms, including nausea and headache, which are characterised as
      'simulator sickness'. Sensory mismatch has been thought to lie at the heart of
      the problem and recent studies have shown that reducing cue mismatch in VR can
      have a therapeutic effect. Specifically, electrical stimulation of vestibular
      afferent nerves (galvanic vestibular stimulation; GVS) can reduce simulator
      sickness in VR. However, GVS poses a risk to certain populations and can also
      result in negative symptoms in normal, healthy individuals. Here, we tested
      whether noisy vestibular stimulation through bone-vibration can also reduce
      symptoms of simulator sickness. We carried out two experiments in which
      participants performed a spatial navigation task in VR and completed the
      Simulator Sickness Questionnaire over a series of trials. Experiment 1 was
      conducted using a high-end projection-based VR display, whereas Experiment 2
      involved the use of a consumer head mounted display. During each trial,
      vestibular stimulation was either: 1) absent; 2) coupled with large angular
      accelerations of the projection camera; or 3) applied randomly throughout each
      trial. In half of the trials, participants actively navigated using a motion
      controller, and in the other half they were moved passively through the
      environment along pre-recorded motion trajectories. In both experiments we
      obtained lower simulator sickness scores when vestibular stimulation was coupled
      with angular accelerations of the camera. This effect was obtained for both
      active and passive movement control conditions, which did not differ. The results
      suggest that noisy vestibular stimulation can reduce simulator sickness, and that
      this effect appears to generalize across VR conditions. We propose further
      examination of this stimulation technique.

PMID- 29590148
TI  - Gender, nutritional status and disability-free life expectancy among older people
      in Santiago, Chile.
AB  - BACKGROUND: This study was aimed to estimate life expectancy (LE), disability
      free life expectancy (DFLE) and disabled life expectancy (DLE) among older adults
      from Santiago, Chile, and to determine the existence of differences by gender and
      by body mass index (BMI) categories in these indicators. METHODS: A sample of
      1216 people aged 60 or more, from the Chilean cohort of the Study of Health,
      Ageing and Well-Being was recruited in 2000; two follow-up assessments were
      carried out in a 10-year period. Functional limitation was assessed through self
      report of difficulties in activities of daily living, instrumental activities of
      daily living and mobility. BMI was determined with measured weight and height.
      Multistate life tables were employed to estimate LE and healthy life expectancy
      (HLE). RESULTS: At 60 years, women could expect to live on average an additional
      20.4 years (95% CI 19.0-21.6), and men an additional 16.4 years (95% CI 14.9
      17.7). Total LE was longer among women at all ages, but they had a higher
      proportion of disabled years to be lived compared to men, with a difference of
      14% at 60 years, and 10% at 90 years. There were no significant differences in
      LE, DFLE and DLE between BMI categories. DISCUSSION: Despite a longer LE, Chilean
      older women expect to live a higher proportion of years with disabilities,
      compared to men. Public health programs should address factors affecting LE of
      older men, and those associated with disability among older women.

PMID- 29590149
TI  - Increased ethanol consumption after interruption of fat bingeing.
AB  - There is a marked comorbidity between alcohol abuse and eating disorders,
      especially in the young population. We have previously reported that bingeing on
      fat during adolescence increases the rewarding effects of ethanol (EtOH). The aim
      of the present work was to study if vulnerability to EtOH persists after
      cessation of binge eating. OF1 mice binged on fat (HFB: high-fat binge) during
      adolescence (PND 25-43) and were tested for 15 days after the last access to HFB
      (on PND 59) using the self-administration paradigm, the conditioned place
      preference (CPP) and locomotor sensitization to ethanol. Our results showed that
      after 15 days of cessation of fat ingestion, mice increased their consumption of
      ethanol and showed greater motivation to obtain ethanol. On the other hand, no
      effects were observed in the CPP, while an increased locomotor response to
      ethanol was detected. The present results confirm and extend our previous study
      demonstrating that the compulsive intake of fat induces long-lasting effects on
      the reward system that lead to an increased consumption of EtOH.

PMID- 29590150
TI  - Retention in care among older adults living with HIV in western Kenya: A
      retrospective observational cohort study.
AB  - BACKGROUND: Retention, defined as continuous engagement in care, is an important
      indicator for quality of healthcare services. To achieve UNAIDS 90-90-90 targets,
      emphasis on retention as a predictor of viral suppression in patients initiated
      on ART is vital. Using routinely collected clinical data, the authors sought to
      determine the effect of age on retention post ART initiation. METHODS: De
      identified electronic data for 32965 HIV-infected persons aged >=15 years at
      enrolment into the Academic Model Providing Access to Healthcare program between
      January 2008 and December 2014 were analyzed. Follow-up time was defined from the
      date of ART initiation until either loss to follow-up or death or close of the
      database (September 2016) was observed. Proportions were compared using Pearson's
      Chi-square test and medians using Mann-Whitney U test. Logistic regression model
      was used to assess differences in ART initiation between groups, adjusting for
      baseline characteristics. Cox proportional hazards model adjusting for baseline
      characteristics and antiretroviral therapy (ART) status was used to compute
      hazard ratios. Kaplan-Meier survival function was used to compare retention on
      ART at 12, 24, and 36 months post ART initiation. RESULTS: Of the total sample,
      3924 (12.0%) were aged >=50 years at enrolment. The median (IQR) age of young
      adults and older adults were 32.5 (26.6, 36.9) and 54.9 (51.7, 59.9)
      respectively. ART initiation rates were 70.5% among older adults and 68.2% among
      younger adults. Retention rates in care at 12, 24 and 36 months post ART
      initiation were 73.9% (95% CL: 72.2, 75.5), 62.9% (95% CL: 61.0, 64.7) and 55.4%
      (95% CL: 53.5, 57.3) among older adults compared to 69.8% (95% CL: 69.1, 70.4),
      58.1% (95% CL: 57.4, 58.8) and 49.3% (95% CL: 48.6, 50.0) among younger adults (p
      <0.001). A higher proportion of older adults were retained in HIV care post ART
      initiation compared to younger adults, Adjusted Hazard Ratio (AHR): 0.83 (95% CI:
      0.78, 0.87) though they were more likely to die, AHR: 1.35 (95% CI: 1.19, 1.52).
      CONCLUSION: A higher proportion of older adults are initiated on ART and have
      better retention in care at 12, 24 and 36 months post ART initiation than younger
      adults. However, older adults have a higher all-cause mortality rate, perhaps
      partially driven by late presentation to care. Enhanced outreach and care to this
      group is imperative to improve their outcomes.

PMID- 29590151
TI  - Untreated depression among persons living with human immunodeficiency virus in
      Kazakhstan: A cross-sectional study.
AB  - BACKGROUND: In Kazakhstan, scarce official prevalence data exists for mood
      disorders. This study investigates the occurrence of depressive symptoms among
      people living with HIV/AIDS (PLWHA), and the relationship between depressive
      symptoms, HIV treatment initiation and antiretroviral treatment (ART) adherence.
      METHODS: A cross-sectional study was conducted among patients seen at the Almaty
      AIDS Center between April and December 2013. Two data sources were used: 1) self
      administered survey that included the Patient Health Questionnaire (PHQ-9) to
      capture depression symptoms and 2) medical record review. Two primary outcomes
      were evaluated with log-binomial models and Fisher's exact test: the relationship
      between depression symptoms and 1) HIV treatment group, and 2) HIV adherence.
      RESULTS: Of the 564 participants, 9.9% reported symptoms consistent with a
      depressive disorder. None had received treatment for depression. Among those not
      on ART, a relationship between depressive symptoms and low CD4 counts (<= 350
      cells/mm3) was evident (7.1% for CD4 <= 350 cells/mm3 vs. 0.9% for CD4 > 350
      cells/mm3, p = 0.029). In multivariable analysis, a higher prevalence of
      depressive symptoms was statistically associated with ART treatment, positive
      hepatitis C virus (HCV) status, and being unmarried. For those taking ART,
      treatment adherence was not statistically associated with a lower prevalence of
      depressive symptoms (12.5% vs 20.0%, p = 0.176); limited power may have impacted
      statistical significance. CONCLUSIONS: Untreated depression was found among PLWHA
      suggesting the need to evaluate access to psychiatric treatment. A collaborative
      strategy may be helpful to optimize HIV treatment outcomes.

PMID- 29590152
TI  - Clinical spectrum and prognostic factors of possible UIP pattern on high
      resolution CT in patients who underwent surgical lung biopsy.
AB  - BACKGROUND: Few studies have reported the diagnostic variability in patients with
      a possible usual interstitial pneumonia (UIP) pattern on high-resolution CT
      (HRCT) who underwent surgical lung biopsy (SLB), and the prognostic factors for
      these patients have not been fully evaluated. We retrospectively investigated the
      frequency of idiopathic pulmonary fibrosis (IPF) and prognostic factors in
      patients with possible UIP pattern on HRCT. METHODS: Consecutive patients who had
      a possible UIP pattern on HRCT, underwent SLB, and had a diagnosis of IIPs before
      SLB were retrospectively recruited from 10 hospitals. Diagnoses were made based
      on multidisciplinary discussion using the criteria for current IPF guidelines and
      multidisciplinary classification for IIPs in each hospital. RESULTS: 179 patients
      who underwent SLB were enrolled. The diagnoses were IPF in 91 patients (51%),
      unclassifiable IIPs in 47 (26%), idiopathic NSIP in 18 (10%), and chronic
      hypersensitivity pneumonia in 17 (9%). One-year FVC changes showed significant
      differences between IPF and non-IPF (-138.6 mL versus 18.2 mL, p = 0.014).
      Patients with IPF had a worse mortality than those with non-IPF (Logrank test, p
      = 0.025). Multivariable Cox regression analysis demonstrated that diagnoses of
      IPF (HR, 2.961; 95% CI, 1.183-7.410; p = 0.02), high modified MRC score (HR,
      1.587; 95% CI, 1.003-2.510; p = 0.049), and low %FVC (HR, 0.972; 95% CI, 0.953
      0.992; p = 0.005). CONCLUSIONS: About a half of patients with a possible UIP
      pattern on HRCT had diagnoses other than IPF, and patients with IPF had a worse
      mortality than those with an alternative diagnosis. We reaffirmed that
      multidisciplinary discussion is crucial in patients with possible UIP pattern on
      HRCT.

PMID- 29590153
TI  - Mechanisms for type-II vitellogenesis-inhibiting hormone suppression of
      vitellogenin transcription in shrimp hepatopancreas: Crosstalk of GC/cGMP pathway
      with different MAPK-dependent cascades.
AB  - Vitellogenesis is the process of yolk formation via accumulating vitellin (Vn)
      with nutrients in the oocytes. Expression of vitellogenin (Vg), the precursor of
      Vn, is one of the indicators for the start of vitellogenesis. In Pacific white
      shrimp (Litopenaeus vannamei), the type-II vitellogenesis-inhibiting hormone (VIH
      2) effectively suppresses hepatopancreatic Vg mRNA expression. In this study, we
      demonstrate the increasing transcript levels of hepatopancreatic Vg during L.
      vannamei ovarian development, suggesting that the hepatopancreas-derived Vg/Vn
      may also contribute to vitellogenesis in this species. Using a combination of in
      vivo injections and in vitro primary cell cultures, we provide evidences that the
      inhibition of VIH-2 on hepatopancreatic Vg gene expression is mediated through a
      functional coupling of the GC/cGMP pathway with different MAPK-dependent cascades
      in female shrimp. In VIH-2 signaling, the NO-independent GC/cGMP/PKG cascades
      were upstream of the MAPKs. Activations of the MAPK signal by VIH-2 include the
      phosphorylation of JNK and the mRNA/protein expression of P38MAPK. Additionally,
      the cAMP/PKA pathway is another positive intracellular signal for
      hepatopancreatic Vg mRNA expression but is independent of its VIH-2 regulation.
      Our findings establish a model for the signal transduction mechanism of Vg
      regulation by VIH and shed light on the biological functions and signaling of the
      CHH family in crustaceans.

PMID- 29590154
TI  - Na+/K+ ATPase activity promotes invasion of endocrine resistant breast cancer
      cells.
AB  - BACKGROUND: The Na+/K+-ATPase (NKP) is an important ion transporter also involved
      in signal transduction. Its expression profile is altered in various tumours
      including that of the breast. We studied the effect of inhibiting NKP activity in
      non-tumorigenic breast cell line and in estrogen receptor positive and negative
      breast cancer cells. METHODS: Expression and localization of NKP and downstream
      signaling molecules were determined by RT-PCR, western blotting and
      immunofluorescence. Cell proliferation, apoptosis and cell cycle stage were
      determined using MTT, annexin V and flow cytometry. Cell motility and invasion
      were determined using wound healing and matrigel assays. Total matrix
      metalloproteinase (MMP) was determined by a fluorescence-based assay. RESULTS:
      NKP was mainly localized on the cell membrane. Its baseline expression and
      activity were enhanced in breast cancer compared to the non-tumorigenic breast
      cell line. Ouabain and 3,4,5,6-tetrahydroxyxanthone (TTX) treatment significantly
      inhibited NKP activity, which significantly reduced cell proliferation, motility,
      invasion and pH-induced membrane blebbing. EGF stimulation induced
      internalization of NKP from the cell membrane to the cytoplasm. Ouabain inhibited
      EGF-induced phosphorylation of Rac/cdc42, profillin, ERK1/2 and P70S6K.
      CONCLUSIONS: The NKP may offer a novel therapeutic target in breast cancer
      patients who have developed metastasis, aiming to improve therapeutic outcomes
      and enhance survival rate.

PMID- 29590155
TI  - Unravelling biocultural population structure in 4th/3rd century BC Monterenzio
      Vecchio (Bologna, Italy) through a comparative analysis of strontium isotopes,
      non-metric dental evidence, and funerary practices.
AB  - The 4th century BC marks the main entrance of Celtic populations in northern
      Italy. Their arrival has been suggested based on the presence of Celtic customs
      in Etruscan mortuary contexts, yet up to now few bioarchaeological data have been
      examined to support or reject the arrival of these newcomers. Here we use
      strontium isotopes, non-metric dental traits and funerary patterns to unravel the
      biocultural structure of the necropolis of Monterenzio Vecchio (Bologna, Italy).
      Subsamples of our total sample of 38 individuals were analyzed based on different
      criteria characterizing the following analyses: 1) strontium isotope analysis to
      investigate migratory patterns and provenance; 2) non-metric dental traits to
      establish biological relationships between Monterenzio Vecchio, 13 Italian Iron
      age necropolises and three continental and non-continental Celtic necropolises;
      3) grave goods which were statistically explored to detect possible patterns of
      cultural variability. The strontium isotopes results indicate the presence of
      local and non-local individuals, with some revealing patterns of mobility. The
      dental morphology reveals an affinity between Monterenzio Vecchio and Iron Age
      Italian samples. However, when the Monterenzio Vecchio sample is separated by
      isotopic results into locals and non-locals, the latter share affinity with the
      sample of non-continental Celts from Yorkshire (UK). Moreover, systematic
      analyses demonstrate that ethnic background does not retain measurable impact on
      the distribution of funerary elements. Our results confirm the migration of
      Celtic populations in Monterenzio as archaeologically hypothesized on the basis
      of the grave goods, followed by a high degree of cultural admixture between
      exogenous and endogenous traits. This contribution shows that combining different
      methods offers a more comprehensive perspective for the exploration of
      biocultural processes in past and present populations.

PMID- 29590156
TI  - Factors influencing long-term medication non-adherence among diabetes and
      hypertensive patients in Ghana: A qualitative investigation.
AB  - BACKGROUND: Evidence remains limited on why diabetes and hypertensive patients
      admitted to long-term drug therapy miss doses or discontinue medication taking.
      We examined this phenomenon from the perspective of diabetes and hypertension
      patients at a Ghanaian teaching hospital. METHODS: Between July and December
      2015, we conducted a qualitative study targeting caregivers and their patients
      with chronic diabetes and hypertensive on re-admission at the Korle Bu Teaching
      Hospital due to non-adherence to prescribed medication. Participants were sampled
      purposefully and taking through in-depth interviews using an interview guide.
      Notes and audio recordings of interviews were transcribed, managed and coded for
      themes guided by the thematic network analysis recommended by Attride-Stirling.
      RESULTS: Non-adherence was the result of perceptions that the medications are not
      effective for managing the conditions. Patients with these perceptions rejected
      the medications and turned to herbal medicines and spiritual healing as
      therapeutic alternatives, because of their easy accessibility, perceived efficacy
      and affordability. Other factors identified to influence non-adherence included
      polypharmacy practice; tight work schedules; social norms; poor prescription
      instruction by health providers; and knowledge and experience of medication.
      CONCLUSION: Findings suggests the need for health providers to adopt therapeutic
      approaches that take into account patients' beliefs, values and norms in
      administering medications. Sensitisation of patients and caregivers during
      admission on the implication of non-adherence, as well as interventions that
      monitor and provide feedback mechanisms on patients' medication taking behaviour
      holds promise for maximising diabetes and hypertensive medication adherence.

PMID- 29590157
TI  - Hyperopic refractive correction by LASIK, SMILE or lenticule reimplantation in a
      non-human primate model.
AB  - Hyperopia is a common refractive error, apparent in 25% of Europeans. Treatments
      include spectacles, contact lenses, laser interventions and surgery including
      implantable contact lenses and lens extraction. Laser treatment offers an
      expedient and reliable means of correcting ametropia. LASIK is well-established
      however SMILE (small-incision lenticule extraction) or lenticule implantation
      (derived from myopic laser-correction) are newer options. In this study we
      compared the outcomes of hyperopic LASIK, SMILE and lenticule re-implantation in
      a primate model at +2D/+4D treatment. While re-implantation showed the greatest
      regression, broadly comparable refractive results were seen at 3-months with
      SMILE and LASIK (<1.4D of intended), but a greater tendency to regression in +2D
      lenticule reimplantation. Central corneal thickness showed greater variation at
      +2D treatment, but central thickening during lenticule reimplantation at +4D
      treatment was seen (-17+/- 27MUm LASIK, -45 +/- 18MUm SMILE and 28 +/- 17MUm Re
      implantation; p <0.01) with expected paracentral thinning following SMILE.
      Although in vivo confocal microscopy appeared to show higher reflectivity in all
      +4D treatment groups, there were minimal and inconsistent changes in inflammatory
      responses between modalities. SMILE and lenticule re-implantation may represent a
      safe and viable method for treating hyperopia, but further optimization for lower
      hyperopic treatments is warranted.

PMID- 29590158
TI  - Significance of serological markers in the disease course of ulcerative colitis
      in a prospective clinical cohort of patients.
AB  - BACKGROUND & AIMS: To determine the prognostic potential of classic and novel
      serologic antibodies regarding unfavorable disease course in a prospective
      ulcerative colitis (UC) patient cohort, since few and conflicting data are
      available in the literature regarding this matter. METHODS: 187 consecutive
      patients were studied prospectively (median follow-up: 135 months) from a single
      referral IBD center in Hungary. Sera were tested for different IgA/IgG type
      autoantibodies (anti-neutrophil cytoplasmic [ANCA], anti-DNA-bound-lactoferrin
      [anti-LFS], anti-goblet cell [anti-GAB] and anti-pancreatic [PAB: anti-CUZD1 and
      anti-GP2)]) by indirect immunofluorescence technique and for anti-microbial (anti
      Saccharomyces cerevisiae [ASCA] IgG/IgA and anti-OMP PlusTM IgA) antibodies by
      enzyme-linked immunosorbent assays. RESULTS: A total of 73.6%, 62.4% and 11.2% of
      UC patients were positive for IgA/IgG type of atypical perinuclear-ANCA, anti-LFS
      and anti-GAB, respectively. Occurrences of PABs were 9.6%, while ASCA IgA/IgG and
      anti-OMP IgA were 17.6% and 19.8%, respectively. Antibody status was stable over
      time. IgA type PABs were more prevalent in patients with primary sclerosing
      cholangitis (37.5% vs. 4.7% for anti-CUZD1 and 12.5% vs. 0% for anti-GP2, p<0.001
      for both). IgA type ASCA and anti-CUZD1 antibodies were associated with higher
      risk of requirement for long-term immunosuppressant therapy in Kaplan-Meier
      analysis (pLogRank <0.01 for both). However, in multivariate Cox-regression
      analysis only ASCA IgA (HR: 2.74, 95%CI: 1.46-5.14, p<0.01) remained independent
      predictor. UC-related hospitalization due to disease activity was only associated
      with multiple antibody positivity (for 3 or more; HR 2.03 [95% CI: 1.16-3.56]; p
      = 0.013). None of the individual antibodies or their combination was associated
      with the risk of development of extensive disease or colectomy. CONCLUSION: Even
      with low prevalence rates, present study gives further evidence to the role of
      certain antibodies as markers for distinct phenotype and disease outcome in UC.
      Considering the result of the multivariate analysis the novel antibodies
      investigated do not seem to be associated with poor clinical outcome in UC, only
      a classic antibody, IgA subtype ASCA remained an independent predictor of long
      term immunosuppressive therapy.

PMID- 29590159
TI  - Motivations of women in Uganda living with rheumatic heart disease: A mixed
      methods study of experiences in stigma, childbearing, anticoagulation, and
      contraception.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is a leading cause of premature
      mortality in low- and middle-income countries (LMICs). Women of reproductive age
      are a unique and vulnerable group of RHD patients, due to increased risk of
      cardiovascular complications and death during pregnancy. Yet, less than 5% of
      women of childbearing age with RHD in LMICs use contraceptives, and one in five
      pregnant women with RHD take warfarin despite known teratogenicity. It is unclear
      whether this suboptimal contraception and anticoagulant use during pregnancy is
      due to lack of health system resources, limited health literacy, or social
      pressure to bear children. METHODS: We conducted a mixed methods study of 75
      women living with RHD in Uganda. Questionnaires were administered to 50 patients.
      Transcripts from three focus groups with 25 participants were analyzed using
      qualitative description methodology. RESULTS: Several themes emerged from the
      focus groups, including pregnancy as a calculated risk; misconceptions about side
      effects of contraceptives and anticoagulation; reproductive decision-making
      control by male partners, in-laws, or physicians; abandonment of patients by male
      partners; and considerable stigma against heart disease patients for both their
      reproductive and financial limitations (often worse than that directed against
      HIV patients). All questionnaire respondents were told by physicians that their
      hearts were not strong enough to support a pregnancy. Only 14% used contraception
      while taking warfarin. All participants felt that society would look poorly on a
      woman who cannot have children due to a heart condition. CONCLUSIONS: To our
      knowledge, this is the first qualitative study of female RHD patients and their
      attitudes toward cardiovascular disorders and reproduction. Our results suggest
      that health programs targeting heart disease in LMICs must pay special attention
      to the needs of women of childbearing age. There are opportunities for improved
      family/societal education programs and community engagement, leading to better
      outcomes and patient empowerment.

PMID- 29590160
TI  - Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene
      expression.
AB  - Omega-6 (n-6) and omega-3 (n-3) long (>= 20 carbon) chain polyunsaturated fatty
      acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis
      of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly
      associated with genetic variation within the fatty acid desaturase (FADS) gene
      cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation
      enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by
      which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues,
      are unclear. The current study examined associations between common single
      nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2
      gene expression in 44 different human tissues (sample sizes ranging 70-361) from
      the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were
      detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each
      gene, False Discovery Rate, FDR<0.05, as defined by GTEx) were identified in 12
      tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six
      tissues had significant (FDR< 0.05) eQTLs associated with both FADS1 and FADS2
      (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly,
      the identified eQTLs were consistently found to be associated in opposite
      directions for FADS1 and FADS2 expression. Taken together, findings from this
      study suggest common SNPs within the FADS gene cluster impact the transcription
      of FADS1 and FADS2 in numerous tissues and raise important questions about how
      the inverse expression of these two genes impact intermediate molecular (such a
      LC-PUFA and LC-PUFA-containing glycerolipid levels) and ultimately clinical
      phenotypes associated with inflammatory diseases and brain health.

PMID- 29590161
TI  - A rat in the sewer: How mental imagery interacts with object recognition.
AB  - The role of mental imagery has been puzzling researchers for more than two
      millennia. Both positive and negative effects of mental imagery on information
      processing have been discussed. The aim of this work was to examine how mental
      imagery affects object recognition and associative learning. Based on different
      perceptual and cognitive accounts we tested our imagery-induced interaction
      hypothesis in a series of two experiments. According to that, mental imagery
      could lead to (1) a superior performance in object recognition and associative
      learning if these objects are imagery-congruent (semantically) and to (2) an
      inferior performance if these objects are imagery-incongruent. In the first
      experiment, we used a static environment and tested associative learning. In the
      second experiment, subjects encoded object information in a dynamic environment
      by means of a virtual sewer system. Our results demonstrate that subjects who
      received a role adoption task (by means of guided mental imagery) performed
      better when imagery-congruent objects were used and worse when imagery
      incongruent objects were used. We finally discuss our findings also with respect
      to alternative accounts and plead for a multi-methodological approach for future
      research in order to solve this issue.

PMID- 29590162
TI  - Clinical and epidemiological characterization of influenza virus infections in
      children with severe acute respiratory infection in Maputo, Mozambique: Results
      from the implementation of sentinel surveillance, 2014 - 2016.
AB  - In Sub-Saharan Africa, where burden, impact, and incidence of acute respiratory
      infections (ARI) are the highest in the world, conversely, the epidemiology of
      influenza-associated severe acute respiratory infections (SARI) is incompletely
      known. The aim of this study was to describe the clinical and epidemiological
      features of influenza-associated SARI in hospitalized children in Maputo city,
      Mozambique. Nasopharyngeal and oropharyngeal swabs were collected from children
      aged 0-14 years old who met the case definition for SARI in two hospitals in
      Maputo city after their parents or legal representative consented to participate.
      A structured questionnaire was used to collect clinical and demographic data.
      Typing and subtyping of influenza were performed by real-time PCR. From January
      2014 to December 2016, a total of 2,007 eligible children were recruited, of whom
      1,997 (99.5%) were screened for influenza by real-time PCR. The median age of
      participants was 16.9 months (IQR: 7.0-38.9 months) and 53.9% (1076/1991) were
      male. A total of 77 were positive for influenza, yielding a frequency of 3.9%
      (77/1,991), with the highest frequency being reported in the age group 1-5 years
      old. Cases of influenza peaked twice each year, during which, its frequency
      reached up to 60%-80%. Among all influenza confirmed cases, 33.7% (26/77), 35.1%
      (27/77) and 28.6% (22/77) were typed as influenza A/H3N2, A/H1N1pdm09, and B,
      respectively. This represents the first report of influenza in urban/sub urban
      setting in Mozambique and the first evidence of distribution of strains of
      influenza in the country. Our data showed that frequency of influenza was lower
      than reported in a rural setting in Mozambique and the frequency of seasonal
      (A/H1N1pdm09) and (A/H3N2) subtypes were similar in children with SARI.

PMID- 29590164
TI  - Differentiating percussion pits and carnivore tooth pits using 3D reconstructions
      and geometric morphometrics.
AB  - During the end of the 20th century and the beginning of the 21st century the
      discussion on early human behavioral patterns revolved around the hunting versus
      scavenging debate. The correct identification of bone modifications, including
      percussion, cut and tooth marks, is a key issue within this debate. While many
      authors have shown that carnivore and human modifications can be easily
      distinguished, it is true that sometimes percussion marks without associated
      microstriations and tooth pits overlap morphologically, causing confusion,
      especially when unmodified hammerstones are used. In order to solve this
      equifinality problem, many investigations have focused their efforts on other
      pieces of evidence such as the identification of notches, fragmentation patterns
      and frequencies, among others. These studies, however, cannot be considered as
      fully conclusive. Within this paper we address the problem of equifinality when
      identifying percussion marks produced with unmodified hammerstones and tooth pits
      created by carnivores using new methodologies based on the 3D reconstruction of
      marks and their statistical multivariate analysis. For the purpose of this study
      a total of 128 marks- 39 percussion marks produced with an unmodified quartzite
      hammerstone, and 89 pits generated by different carnivores-were virtually
      modelled with the aid of a DAVID structured-light scanner SLS-2 and later
      analyzed by means of geometric morphometrics. Our results show that percussion
      marks not associated with striae fields and the pits generated by the carnivores
      studied here can be successfully distinguished.

PMID- 29590163
TI  - Fresh red blood cells transfusion protects against aluminum phosphide-induced
      metabolic acidosis and mortality in rats.
AB  - BACKGROUND: Aluminum phosphide (AlP) is used as pesticide in some countries for
      protection of stored grains. Human poisoning with AlP due to suicide attempt or
      accidental environmental exposure is associated with very high mortality
      partially due to development of severe metabolic acidosis. Previous studies have
      shown that hemoglobin has high buffering capacity and erythrocytes can
      potentially be used for management of metabolic acidosis. The aim of this study
      was to evaluate the effect of fresh packed red blood cells (RBC) transfusion on
      survival and cardiovascular function in AlP-poisoned rats. METHODOLOGY/PRINCIPAL
      FINDINGS: Rats were poisoned with AlP by gavage. Fresh packed RBC was transfused
      via tail vein after AlP administration. Acid-base balance, vital signs and
      mortality was assessed and compared in experimental groups. Infusion of fresh
      packed RBC (1.5 ml) one hour after AlP (4-15 mg/kg) intoxication was associated
      with a significant decrease in mortality rate. Packed RBC infusion improved blood
      pH, HCO3-, Na+ and Ca2+ levels. Plasma troponin level was also reduced and ECG
      changes were reversed following packed RBC infusion in AlP intoxicated rats.
      CONCLUSIONS: Our results showed that fresh RBC transfusion could ameliorate
      metabolic acidosis and enhance survival in AlP-poisoned rat. We assume that an
      increase in pool of RBCs may modulate acid-base balance or potentially chelate
      AlP-related toxic intermediates via phosphine-hemoglobin interaction.

PMID- 29590165
TI  - Terminal Pleistocene epoch human footprints from the Pacific coast of Canada.
AB  - Little is known about the ice age human occupation of the Pacific Coast of
      Canada. Here we present the results of a targeted investigation of a late
      Pleistocene shoreline on Calvert Island, British Columbia. Drawing upon existing
      geomorphic information that sea level in the area was 2-3 m lower than present
      between 14,000 and 11,000 years ago, we began a systematic search for
      archaeological remains dating to this time period beneath intertidal beach
      sediments. During subsurface testing, we uncovered human footprints impressed
      into a 13,000-year-old paleosol beneath beach sands at archaeological site EjTa
      4. To date, our investigations at this site have revealed a total of 29
      footprints of at least three different sizes. The results presented here add to
      the growing body of information pertaining to the early deglaciation and
      associated human presence on the west coast of Canada at the end of the Last
      Glacial Maximum.

PMID- 29590166
TI  - Tooth loss and risk of cardiovascular disease and stroke: A dose-response meta
      analysis of prospective cohort studies.
AB  - Conflicting results identifying the association between tooth loss and
      cardiovascular disease and stroke have been reported. Therefore, a dose-response
      meta-analysis was performed to clarify and quantitatively assess the correlation
      between tooth loss and cardiovascular disease and stroke risk. Up to March 2017,
      seventeen cohort studies were included in current meta-analysis, involving a
      total of 879084 participants with 43750 incident cases. Our results showed
      statistically significant increment association between tooth loss and
      cardiovascular disease and stroke risk. Subgroups analysis indicated that tooth
      loss was associated with a significant risk of cardiovascular disease and stroke
      in Asia and Caucasian. Furthermore, tooth loss was associated with a significant
      risk of cardiovascular disease and stroke in fatal cases and nonfatal cases.
      Additionally, a significant dose-response relationship was observed between tooth
      loss and cardiovascular disease and stroke risk. Increasing per 2 of tooth loss
      was associated with a 3% increment of coronary heart disease risk; increasing per
      2 of tooth loss was associated with a 3% increment of stroke risk. Subgroup meta
      analyses in study design, study quality, number of participants and number of
      cases showed consistent findings. No publication bias was observed in this meta
      analysis. Considering these promising results, tooth loss might provide harmful
      health benefits.

PMID- 29590167
TI  - Serum vitamin D concentrations in hospitalized critically ill dogs.
AB  - Hypovitaminosis D has been extensively documented in critically ill humans.
      However, whether or not critically ill dogs have alterations in vitamin D
      concentrations remains unconfirmed. The primary aims of our study were to compare
      serum 25-hydroxycholecalciferol [25(OH)D] concentrations in critically ill dogs
      with healthy control dogs, determine the prognostic utility of serum 25(OH)D
      concentration as a biomarker in critically ill dogs, and to assess if serum
      25(OH)D concentrations in critically ill dogs are associated with length of stay
      in the intensive care unit or illness severity. Serum concentrations of 25(OH)D
      together with a range of other clinical, biochemical, and hematological
      parameters, were measured in 99 dogs within 24 hours of admission to the
      Intensive Care Unit (ICU). Critically ill dogs (P = 0.001) and dogs with sepsis
      (P = 0.002) had significantly lower serum 25(OH)D concentrations compared to
      healthy control dogs. In addition, serum 25(OH)D concentration was an independent
      predictor of in-hospital and 30 day survival. Using a cut-off of 33 ng/mL, serum
      25(OH)D concentrations had excellent sensitivity (0.94; 95% CI, 0.71-1.00), but
      poor specificity (0.41; 95% CI, 0.31-0.53) for detection of survival. Serum
      25(OH)D concentrations were inversely associated with acute patient physiologic
      and laboratory evaluation (APPLE) fast score but were not associated with ICU
      length of stay. Hospitalized dogs with critical illness have decreased serum
      25(OH)D concentrations compared to healthy dogs and can be used to predict
      survival in this cohort.

PMID- 29590168
TI  - Just ask Siri? A pilot study comparing smartphone digital assistants and laptop
      Google searches for smoking cessation advice.
AB  - OBJECTIVE: To compare voice-activated internet searches by smartphone (two
      digital assistants) with laptop ones for information and advice related to
      smoking cessation. DESIGN: Responses to 80 questions on a range of topics related
      to smoking cessation (including the FAQ from a NHS website), compared for
      quality. SETTING: Smartphone and internet searches as performed in New Zealand.
      MAIN OUTCOME MEASURES: Ranked responses to the questions. RESULTS: Google laptop
      internet searches came first (or first equal) for best quality smoking cessation
      advice for 83% (66/80) of the responses. Voiced questions to Google Assistant
      ("OK Google") came first/first equal 76% of the time vs Siri (Apple) at 28%.
      Google and Google Assistant were statistically significantly better than Siri
      searches (odds ratio 12.4 and 8.5 respectively, p<0.0001 in each comparison).
      When asked FAQs from the National Health Service website, or to find information
      the Centers for Disease Control has made videos on, the best search results used
      expert sources 59% (31/52) of the time, "some expertise" (eg, Wikipedia) 18% of
      the time, but also magazines and other low quality sources 19% of the time. Using
      all three methods failed to find relevant information 8% (6/80) of the time, with
      Siri having the most failed responses (53% of the time). CONCLUSION: Google
      internet searches and Google Assistant were found to be significantly superior to
      the Siri digital assistant for smoking cessation information. While expert
      content was returned over half the time, there is still substantial room for
      improvement in how these software systems deliver smoking cessation advice.

PMID- 29590169
TI  - Traction force microscopy of engineered cardiac tissues.
AB  - Cardiac tissue development and pathology have been shown to depend sensitively on
      microenvironmental mechanical factors, such as extracellular matrix stiffness, in
      both in vivo and in vitro systems. We present a novel quantitative approach to
      assess cardiac structure and function by extending the classical traction force
      microscopy technique to tissue-level preparations. Using this system, we
      investigated the relationship between contractile proficiency and metabolism in
      neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking
      soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa)
      cardiac microenvironments. We found that tissues engineered on the softest gels
      generated the least amount of stress and had the smallest work output.
      Conversely, cardiomyocytes in tissues engineered on healthy- and disease
      mimicking gels generated significantly higher stresses, with the maximal
      contractile work measured in NRVM engineered on gels of normal stiffness.
      Interestingly, although tissues on soft gels exhibited poor stress generation and
      work production, their basal metabolic respiration rate was significantly more
      elevated than in other groups, suggesting a highly ineffective coupling between
      energy production and contractile work output. Our novel platform can thus be
      utilized to quantitatively assess the mechanotransduction pathways that initiate
      tissue-level structural and functional remodeling in response to substrate
      stiffness.

PMID- 29590170
TI  - Histologic subtypes are not associated with the presence of sarcopenia in lung
      cancer.
AB  - BACKGROUND: Sarcopenia is prevalent and a known adverse prognostic effector in
      lung cancer (LCA). However, the relationship between sarcopenia and histology
      remains uncertain in LCA. METHODS: Consecutive patients with newly diagnosed LCA
      (n = 778) between June 2012 and February 2015 were retrospectively reviewed to
      identify factors associated with sarcopenia. Sarcopenia was defined as CT
      determined L3 muscle index (muscle area at L3/height2) of < 55 cm2/m2 for men and
      < 39 cm2/m2 for women. RESULTS: Mean patient age was 67.7 +/- 10.8 years, and
      most (73.1%) were male. The most prevalent histology was adenocarcinoma (44.0%)
      and 71.6% of patients had stage III or IV disease. The overall prevalence of
      sarcopenia was 48.2% (60.3% in men, and 15.3% in women). Univariable analysis
      showed sarcopenia was significantly associated with male gender, age (>= 65
      years), smoking status, lower BMI (< 23 kg/m2), advanced stage (III and IV), and
      high comorbidity score (Charlson index >= 3). Furthermore, the prevalence of
      sarcopenia was higher in squamous cell carcinoma (54.9%) and small cell LCA
      (56.4%) than in adenocarcinoma (39.8%). Multivariable analyses showed sarcopenia
      was independently associated with a male gender (odds ratio [OR], 11.13), elderly
      (OR, 2.02) and low BMI (OR, 6.28), stage IV (OR, 1.98), and high comorbidity (OR,
      1.93). However, no significant association was found between histologic subtypes
      and sarcopenia. CONCLUSIONS: Sarcopenia was found to be significantly associated
      with old age, male gender, an advanced stage, comorbidities, and low BMI in LCA.
      However, histology subtype was not an independent factor for the presence of
      sarcopenia.

PMID- 29590171
TI  - PARP1 depletion induces RIG-I-dependent signaling in human cancer cells.
AB  - DNA Damage Response (DDR) and DNA repair pathways are emerging as potent,
      ubiquitous suppressors of innate immune signaling in human cells. Here, we show
      that human cells surviving depletion of the Single Strand Break (SSB) repair
      protein PARP1 undergo p21-dependent senescence or cell cycle checkpoint
      activation in the context of activation of innate immune signaling, or viral
      mimicry. Specifically, we observe induction of a large number of interferon
      stimulated genes (ISGs) and multiple pattern recognition receptors (PRRs;
      including RIG-I, MDA-5, MAVS, TLR3 and STING) and increased nuclear IRF3
      staining. Mechanistically, depletion of the double-stranded RNA (dsRNA) helicase
      RIG-I or its downstream effector MAVS specifically rescues ISG induction in PARP1
      depleted cells, suggesting that the RIG-I/MAVS pathway is required for sustained
      ISG expression in this context. Experiments with conditioned media or a
      neutralizing antibody to the alpha/beta-IFN receptor revealed that persistent ISG
      expression additionally requires an autocrine/paracrine loop. Finally, loss of
      PARP1 and radiation-induced DNA damage strongly synergize in the induction of p21
      and ISGs. Overall, these findings increase our understanding of how PARP1 may
      suppress deleterious phenotypes associated to aging, inflammation and cancer in
      humans.

PMID- 29590172
TI  - Complementation of the Mycoplasma synoviae MS-H vaccine strain with wild-type obg
      influencing its growth characteristics.
AB  - The temperature-sensitive (ts+) Mycoplasma synoviae vaccine strain MS-H harbors a
      non-synonymous mutation which results in Glycine to Arginine substitution at
      position 123 in the highly conserved glycine-rich motif of Obg-fold in the GTP
      binding protein Obg. In-silico analysis of the wild-type and mutant Obgs of M.
      synoviae has indicated that this amino acid substitution affects structure of the
      protein, potentially leading to abrogation of Obg function in vivo. Present study
      was conducted to develop the first expression vector for M. synoviae and to
      investigate the potential effect(s) of complementation of MS-H vaccine with the
      wild-type obg from 86079/7NS, the parent strain of MS-H. An oriC vector, pKS
      VOTL, harboring the 86079/7NS obg gene, downstream of the variable lipoprotein
      haemagglutinin (vlhA) gene promoter, also cloned from 86079/7NS, was used to
      transform MS-H. The plasmid was localised at the chromosomal oriC locus of MS-H
      without any detectable integration at the chromosomal obg locus. Analysis of the
      MS-H transformants revealed abundant obg transcripts as well as Obg protein, when
      compared to the MS-H transformed with a similar vector, pMAS-LoriC, lacking obg
      coding sequence. The MS-H transformants complemented with wild-type Obg
      maintained their original temperature-sensitivity phenotype (consistent with MS-H
      vaccine) but, when compared to the MS-H transformed with pMAS-LoriC, had
      significantly higher (p < 0.05) growth rate and viability at the permissive (33
      degrees C) and non-permissive temperature (39.5 degrees C), respectively.
      Analysis of Obg expression in MS-H and its wild-type parent strain revealed
      comparatively lower levels of Obg in MS-H. These results indicate that not only
      the mutation in Obg, but also the level of Obg expression, can confer functional
      abnormalities in the bacterial host. Furthermore, with the construction of first
      expression vector for M. synoviae, this study has set foundation for the
      development of recombinant vaccine(s) based on MS-H.

PMID- 29590173
TI  - Soluble klotho as a marker of renal fibrosis and podocyte injuries in human
      kidneys.
AB  - Klotho deficiency is relevant to renal fibrosis and podocyte injury in vivo and
      in vitro. We examined whether histological findings of renal biopsy specimens
      were associated with the levels of soluble klotho in humans. We investigated
      renal biopsy specimens of 67 patients and detailed microscopic findings were
      reviewed. Soluble serum/urinary klotho and urinary angiotensinogen were assessed
      by enzyme-linked immunosorbent assays, and tissue klotho expression was assessed
      by immunohistochemical staining. The median age of the study participants was
      35.6 years. High serum klotho levels (>=14 pg/mL) were associated with decreased
      odds ratios (ORs) of interstitial fibrosis (OR = 0.019, P = 0.003) and segmental
      sclerosis (OR = 0.190, P = 0.022) in multivariable logistic regression analysis.
      Patients with a lower urinary klotho-to-creatinine ratio (UKCR) were
      significantly more likely to have diffuse foot process effacement (OR = 0.450, P
      = 0.010). The area under the receiver-operating characteristic curve (AUC) of
      serum klotho for predicting interstitial fibrosis was 0.920 (95% CI, 0.844
      0.996), and the best cut-off value of serum klotho was 138.1 pg/mL. The AUC of
      UKCR for predicting diffuse foot process effacement was 0.754 (95% CI, 0.636
      0.872), and the best cut-off value of UKCR was 96.7 pg/mgCr. Urinary
      angiotensinogen-to-creatinine ratio was not associated with serum klotho, UKCR,
      or any pathological finding. Our data suggested that soluble serum and urinary
      klotho levels represent a potential biomarker to predict renal fibrosis and
      podocyte injury in humans.

PMID- 29590174
TI  - Extending the paleontology-biogeography reciprocity with SDMs: Exploring models
      and data in reducing fossil taxonomic uncertainty.
AB  - Historically, studies aimed at prospecting and analyzing paleontological and
      neontological data to investigate species distribution have developed separately.
      Research at the interface between paleontology and biogeography has shown a
      unidirectional bias, mostly focusing on how paleontological information can aid
      biogeography to understand species distribution through time. However, the modern
      suit of techniques of ecological biogeography, particularly species distribution
      models (SDM), can be instrumental for paleontologists as well, improving the
      biogeography-paleontology interchange. In this study, we explore how to use
      paleoclimatic data and SDMs to support paleontological investigation regarding
      reduction of taxonomic uncertainty. Employing current data from two neotropical
      species (Lagostomus maximus and Myocastor coipus), we implemented SDMs and
      performed model validation comparing hindcasts with dated fossil occurrences
      (~14k and ~20k years back present, respectively). Finally, we employed the
      hindcasting process for two South American fossil records of a misidentified
      species of caiman (Caiman sp.) to show that C. latirostris is the most likely
      species identity of these fossils (among four candidate species: C. latirostris,
      C. yacare, C. crocodilus, and Melanosuchus niger). Possible limitations of the
      approach are discussed. With this strategy, we have shown that current
      developments in biogeography research can favour paleontology, extending the
      (biased) current interchange between these two scientific disciplines.

PMID- 29590175
TI  - Diet and hygiene practices influence morbidity in schoolchildren living in
      Schistosomiasis endemic areas along Lake Victoria in Kenya and Tanzania-A cross
      sectional study.
AB  - BACKGROUND: Since 2011, cohorts of schoolchildren in regions bordering Lake
      Victoria in Kenya and Tanzania have been investigated for morbidity caused by
      Schistosoma mansoni infection. Despite being neighbouring countries with similar
      lifestyles and ecological environments, Tanzanian schoolchildren had lower S.
      mansoni prevalence and intensity and they were taller and heavier, fewer were
      wasted and anaemic, and more were physical fit compared to their Kenyan peers.
      The aim of the present study was to evaluate whether diet and school-related
      markers of socioeconomic status (SES) could explain differences in morbidity
      beyond the effect of infection levels. METHODS AND PRINCIPAL FINDINGS:
      Parasitological and morbidity data from surveys in 2013-2014 were compared with
      information on diet and school-related markers of SES collected in 2015 using
      questionnaires. A total of 490 schoolchildren (163 Kenyans and 327 Tanzanians)
      aged 9-11 years provided data. A higher proportion of Tanzanian pupils (69.4%,
      95% CI: 64.3-74.5) knew where to wash hands after toilet visits compared to
      Kenyan pupils (48.5%, 95% CI: 40.9-56.1; P<0.0005). Similar proportions of
      children in the two countries ate breakfast, lunch and dinner, but the content of
      the meals differed. At all three meals, a higher proportion (95% CI) of Tanzanian
      pupils consumed animal proteins (mostly fish proteins) compared to their Kenyan
      peers (35.0% (28.3-41.7) vs. 0%; P<0.0005 at breakfast; 69.0% (63.9-74.1) vs.
      43.6% (35.8-51.4); P<0.0005 at lunch; and 67.2% (62.1-72.3) vs. 53.4% (45.8
      61.0); P = 0.003 at dinner). Multivariable analyses investigating risk factors
      for important morbidity markers among individuals revealed that after controlling
      for schistosome and malaria infections, eating animal proteins (fish) and knowing
      where to wash hands after toilet visits were significant predictors for both
      haemoglobin levels and physical fitness (measured as VO2 max). CONCLUSIONS: These
      results suggest that the differences in morbidity may be affected by factors
      other than S. mansoni infection alone. Diet and hygiene practice differences were
      associated with health status of schoolchildren along Lake Victoria in Kenya and
      Tanzania. TRIAL REGISTRATION: Trials Registration numbers: ISRCT 16755535
      (Kenya), ISRCT 95819193 (Tanzania).

PMID- 29590176
TI  - Differential models of twin correlations in skew for body-mass index (BMI).
AB  - BACKGROUND: Body Mass Index (BMI), like most human phenotypes, is substantially
      heritable. However, BMI is not normally distributed; the skew appears to be
      structural, and increases as a function of age. Moreover, twin correlations for
      BMI commonly violate the assumptions of the most common variety of the classical
      twin model, with the MZ twin correlation greater than twice the DZ correlation.
      This study aimed to decompose twin correlations for BMI using more general skew-t
      distributions. METHODS: Same sex MZ and DZ twin pairs (N = 7,086) from the
      community-based Washington State Twin Registry were included. We used latent
      profile analysis (LPA) to decompose twin correlations for BMI into multiple
      mixture distributions. LPA was performed using the default normal mixture
      distribution and the skew-t mixture distribution. Similar analyses were performed
      for height as a comparison. Our analyses are then replicated in an independent
      dataset. RESULTS: A two-class solution under the skew-t mixture distribution fits
      the BMI distribution for both genders. The first class consists of a relatively
      normally distributed, highly heritable BMI with a mean in the normal range. The
      second class is a positively skewed BMI in the overweight and obese range, with
      lower twin correlations. In contrast, height is normally distributed, highly
      heritable, and is well-fit by a single latent class. Results in the replication
      dataset were highly similar. CONCLUSIONS: Our findings suggest that two distinct
      processes underlie the skew of the BMI distribution. The contrast between height
      and weight is in accord with subjective psychological experience: both are under
      obvious genetic influence, but BMI is also subject to behavioral control, whereas
      height is not.

PMID- 29590177
TI  - Emergence of Orientia tsutsugamushi as an important cause of Acute Encephalitis
      Syndrome in India.
AB  - BACKGROUND: Acute Encephalitis Syndrome (AES) is a major seasonal public health
      problem in Bihar, India. Despite efforts of the Bihar health department and the
      Government of India, burden and mortality of AES cases have not decreased, and
      definitive etiologies for the illness have yet to be identified. OBJECTIVES: The
      present study was undertaken to study the specific etiology of AES in Bihar.
      METHODS: Cerebrospinal fluid and/or serum samples from AES patients were
      collected and tested for various pathogens, including viruses and bacteria by
      ELISA and/or Real Time PCR. FINDINGS: Of 540 enrolled patients, 33.3% (180)
      tested positive for at least one pathogen of which 23.3% were co-positive for
      more than one pathogen. Most samples were positive for scrub typhus IgM or PCR
      (25%), followed by IgM positivity for JEV (8.1%), WNV (6.8%), DV (6.1%), and
      ChikV (4.5%).M. tuberculosis and S. pneumoniae each was detected in ~ 1% cases.
      H. influenzae, adenovirus, Herpes Simplex Virus -1, enterovirus, and measles
      virus, each was detected occasionally. The presence of Scrub typhus was confirmed
      by PCR and sequencing. Bihar strains resembled Gilliam-like strains from
      Thailand, Combodia and Vietnam. CONCLUSION: The highlights of this pilot AES
      study were detection of an infectious etiology in one third of the AES cases,
      multiple etiologies, and emergence of O. tsutsugamushi infection as an important
      causative agent of AES in India.

PMID- 29590178
TI  - Recombinant Zika virus envelope protein elicited protective immunity against Zika
      virus in immunocompetent mice.
AB  - Zika virus (ZIKV) has caused great public concerns due to its recent large
      outbreaks and a close association with microcephaly in fetus and Guillain-Barre
      syndrome in adults. Rapid development of vaccines against ZIKV is a public health
      priority. To this end, we have constructed and purified recombinant ZIKV envelope
      protein using both prokaryotic and eukaryotic expression systems, and then tested
      their immunogenicity and protective efficacy in immune competent mice. Both
      protein immunogens elicited humoral and cellular immune responses, and protected
      immune competent mice from ZIKV challenge in vivo. These products could be
      further evaluated either as stand-alone vaccine candidate, or used in a prime-and
      boost regimen with other forms of ZIKV vaccine.

PMID- 29590179
TI  - Influence of fast advective flows on pattern formation of Dictyostelium
      discoideum.
AB  - We report experimental and numerical results on pattern formation of self
      organizing Dictyostelium discoideum cells in a microfluidic setup under a
      constant buffer flow. The external flow advects the signaling molecule cyclic
      adenosine monophosphate (cAMP) downstream, while the chemotactic cells attached
      to the solid substrate are not transported with the flow. At high flow
      velocities, elongated cAMP waves are formed that cover the whole length of the
      channel and propagate both parallel and perpendicular to the flow direction.
      While the wave period and transverse propagation velocity are constant, parallel
      wave velocity and the wave width increase linearly with the imposed flow. We also
      observe that the acquired wave shape is highly dependent on the wave generation
      site and the strength of the imposed flow. We compared the wave shape and
      velocity with numerical simulations performed using a reaction-diffusion model
      and found excellent agreement. These results are expected to play an important
      role in understanding the process of pattern formation and aggregation of D.
      discoideum that may experience fluid flows in its natural habitat.

PMID- 29590180
TI  - Pre-treatment tumour perfusion parameters and initial RECIST response do not
      predict long-term survival outcomes for patients with head and neck squamous cell
      carcinoma treated with induction chemotherapy.
AB  - OBJECTIVES: Previously, we showed that pre-treatment tumour plasma perfusion (Fp)
      predicts RECIST response to induction chemotherapy (ICT) in locoregionally
      advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to
      determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or
      RECIST response post 2 cycles of ICT were prognostic for long-term survival
      outcomes. METHODS: A prospective study enrolled patients with high stage HNSCC
      treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed
      by synchronous cisplatin and intensity modulated radiotherapy. Dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) before and after two cycles of ICT
      was used to measure Fp and RECIST response. RESULTS: Forty-two patients were
      recruited and 37 underwent two scans. The median follow-up was 36 (range 23-49)
      months. Pre-treatment tumour Fp (stratified by median) was not prognostic for
      overall survival (p = 0.42), disease specific survival (p = 0.20) and
      locoregional control (p = 0.64). Neither change in tumour Fp nor RECIST response
      post two cycles of ICT was prognostic for any outcome (p>0.21). CONCLUSION: DCE
      MRI parameters do not predict long-term survival outcomes following ICT and
      RECIST response to ICT may not be an appropriate endpoint to determine early
      efficacy of a treatment in HNSCC patients.

PMID- 29590181
TI  - Modulation of inhibitory control by prefrontal anodal tDCS: A crossover double
      blind sham-controlled fMRI study.
AB  - Prefrontal anodal transcranial direct current stimulation (tDCS) has been
      proposed as a potential approach to improve inhibitory control performance. The
      functional consequences of tDCS during inhibition tasks remain, however, largely
      unresolved. We addressed this question by analyzing functional magnetic resonance
      imaging (fMRI) recorded while participants completed a Go/NoGo task after right
      lateralized prefrontal anodal tDCS with a crossover, sham-controlled, double
      blind experimental design. We replicated previous evidence for an absence of
      offline effect of anodal stimulation on Go/NoGo performance. The fMRI results
      revealed a larger increase in right ventrolateral prefrontal activity for Go than
      NoGo trials in the anodal than sham condition. This pattern suggests that tDCS
      induced increases in cortical excitability have larger effects on fMRI activity
      in regions with a lower task-related engagement. This was the case for the right
      prefrontal cortex in the Go condition in our task because while reactive
      inhibition was not engaged during execution trials, the unpredictability of the
      demand for inhibitory control still incited an engagement of proactive
      inhibition. Exploratory analyses further revealed that right prefrontal
      stimulation interacted with task-related functional demands in the supplementary
      motor area and the thalamus. Our collective results emphasize the dependency of
      offline tDCS functional effects on the task-related engagement of the stimulated
      areas and suggest that this factor might partly account for the discrepancies in
      the functional effects of tDCS observed in previous studies.

PMID- 29590182
TI  - Clinical endpoints in the controlled human challenge model for Shigella: A call
      for standardization and the development of a disease severity score.
AB  - BACKGROUND: Since 1946 the controlled human infection model (CHIM) for Shigella
      has been used to improve understanding of disease pathogenesis, describe clinical
      and immunologic responses to infection and as a tool for vaccine development. As
      the frequency and intent for use in vaccine comparisons increases,
      standardization of the primary endpoint definition is necessary. METHODS: Subject
      level data were obtained from previously conducted experimental Shigella CHIM
      studies. Signs and symptoms severity were categorized consistently across all
      studies. Sign and symptom correlations were estimated and univariate models were
      utilized to describe the association between stool output and other Shigella
      attributable signs and symptoms. Multiple correspondence and hierarchical
      clustering analyses were performed to describe the co-occurrence of signs and
      symptoms. A disease score is proposed based on the co-occurrence of these events.
      RESULTS: Data were obtained on 54 subjects receiving 800 to 2000 colony forming
      units (cfu) of S. flexneri. The median maximum 24 hour stool output was 514 ml
      (IQR: 300, 998 ml) with a median frequency of 6 (IQR: 4, 9). Subjects reported
      abdominal pain or cramps (81.5%), headache (66.7%) and anorexia (64.8%), 50.0%
      had a fever and 27.8% had gross blood in multiple loose stools. Multiple
      correspondence analyses highlighted co-occurrence of symptoms based on severity.
      A 3-parameter disease severity score predicted shigellosis endpoints and better
      differentiated disease spectrum. CONCLUSION: Dichotomous endpoints for Shigella
      CHIM fail to fully account for disease variability. An ordinal disease score
      characterizing the breadth of disease severity may enable a better
      characterization of shigellosis and can decrease sample size requirements.
      Furthermore, the disease severity score may be a useful tool for portfolio
      management by enabling prioritization across vaccine candidates with comparable
      efficacy estimates using dichotomous endpoints.

PMID- 29590183
TI  - High health literacy is associated with less obesity and lower Framingham risk
      score: Sub-study of the VGH-HEALTHCARE trial.
AB  - BACKGROUNDS: Lower health literacy (HL) is associated with several cardiovascular
      disease (CVD) risk factors such as diabetes, hypertension, and metabolic syndrome
      (MS). The aim of our study was to investigate the association between HL and the
      Framingham 10-year risk score of CVD. METHODS: From 2015-2016, 1010 subjects aged
      23 to 88 years receiving health check-up in Taipei Veterans General Hospital had
      complete clinical evaluations and laboratory examinations. Fatty liver was
      diagnosed by ultrasonography. The short form questionnaire adapted from the
      Mandarin Health Literacy Scale was used to assess HL. The Framingham risk score
      was calculated by patient characteristics. RESULTS: Subjects with higher BMIs
      were associated with lower HL scores. The proportion of subjects with MS was
      higher in the lower health literacy score group (<= 9) at 28.8%; further analysis
      found that lower HL was significantly associated with MS in women but not in men.
      The Spearman's rho demonstrated that the HL score was significantly associated
      with the BMI-based (rho = -0.11; P < 0.001) or lipid-based (rho = -0.09; P <
      0.004) Framingham risk score. CONCLUSIONS: Higher HL scores were associated with
      less CVD risk such as lower BMIs, less MS in women, and less fatty liver disease.
      Furthermore, HL had an inverse association with the Framingham risk score as
      expected. Therefore, HL in patients with CVD risk should be improved and
      considered as an important issue in terms of CVD reduction.

PMID- 29590184
TI  - Gene cloning of a neutral ceramidase from the sphingolipid metabolic pathway
      based on transcriptome analysis of Amorphophallus muelleri.
AB  - Amorphophallus is a perennial herbaceous plant species mainly distributed in the
      tropics or subtropics of Asia and Africa. It has been used as a traditional
      medicine for a long time and now is utilized for the pharmaceutical, chemical and
      agriculture industries as a valued economic crop. Recently, Amorphophallus has
      attracted tremendous interest because of its high ceramide content. However, the
      breeding and genome studies are severely limited by the arduous whole genome
      sequencing of Amorphophallus. In this study, the transcriptome data of A.
      muelleri was obtained by utilizing the high-throughput Illumina sequencing
      platform. Based on this information, the majority of the significant genes
      involved in the proposed sphingolipid metabolic pathway were identified. Then,
      the full-length neutral ceramidase cDNA was obtained with the help of its
      candidate transcripts, which were acquired from the transcriptome data.
      Furthermore, we demonstrated that this neutral ceramidase was a real ceramidase
      by eukaryotic expression in the yeast double knockout mutant Deltaypc1 Deltaydc1,
      which lacks the ceramidases-dihydroCDase (YDC1p), phytoCDase (YPC1p). In
      addition, the biochemical characterization of purified A. muelleri ceramidase
      (AmCDase) exhibited classical Michaelis-Menten kinetics with an optimal activity
      ranging from pH 6.5 to 8.0. Based on our knowledge, this study is the first to
      report the related information of the neutral ceramidase in Amorphophallus. All
      datasets can provide significant information for related studies, such as gene
      expression, genetic improvement and application on breeding in Amorphophallus.

PMID- 29590185
TI  - New insights into the genome repetitive fraction of the Antarctic bivalve
      Adamussium colbecki.
AB  - Repetitive DNA represents the major component of the genome in both plant and
      animal species. It includes transposable elements (TEs), which are dispersed
      throughout the genome, and satellite DNAs (satDNAs), which are tandemly organized
      in long arrays. The study of the structure and organization of repetitive DNA
      contributes to our understanding of genome architecture and the mechanisms
      leading to its evolution. Molluscs represent one of the largest groups of
      invertebrates and include organisms with a wide variety of morphologies and
      lifestyles. To increase our knowledge of bivalves at the genome level, we
      analysed the Antarctic scallop Adamussium colbecki. The screening of the genomic
      library evidenced the presence of two novel satDNA elements and the CvA
      transposon. The interspecific investigation performed in this study demonstrated
      that one of the two satDNAs isolated in A. colbecki is widespread in polar
      molluscan species, indicating a possible link between repetitive DNA and abiotic
      factors. Moreover, the transcriptional activity of CvA and its presence in long
      diverged bivalves suggests a possible role for this ancient element in shaping
      the genome architecture of this clade.

PMID- 29590186
TI  - JMJD1A, H3K9me1, H3K9me2 and ADM expression as prognostic markers in oral and
      oropharyngeal squamous cell carcinoma.
AB  - AIMS: Jumonji Domain-Containing 1A (JMJD1A) protein promotes demethylation of
      histones, especially at lysin-9 of di-methylated histone H3 (H3K9me2) or mono
      methylated (H3K9me1). Increased levels of H3 histone methylation at lysin-9
      (H3K9) is related to tumor suppressor gene silencing. JMJD1A gene target
      Adrenomeduline (ADM) has shown to promote cell growth and tumorigenesis. JMJD1A
      and ADM expression, as well as H3K9 methylation level have been related with
      development risk and prognosis of several tumor types. METHODS AND RESULTS: We
      aimed to evaluate JMJD1A, ADM, H3K9me1 and H3K9me2expression in paraffin-embedded
      tissue microarrays from 84 oral and oropharyngeal squamous cell carcinoma samples
      through immunohistochemistry analysis. Our results showed that nuclear JMJD1A
      expression was related to lymph node metastasis risk. In addition, JMJD1A
      cytoplasmic expression was an independent risk marker for advanced tumor stages.
      H3K9me1 cytoplasmic expression was associated with reduced disease-specific death
      risk. Furthermore, high H3K9me2 nuclear expression was associated with worse
      specific-disease and disease-free survival. Finally, high ADM cytoplasmic
      expression was an independent marker of lymph node metastasis risk. CONCLUSION:
      JMJD1A, H3K9me1/2 and ADM expression may be predictor markers of progression and
      prognosis in oral and oropharynx cancer patients, as well as putative therapeutic
      targets.

PMID- 29590187
TI  - Is endotracheal intubation a non-beneficial treatment in patients with
      respiratory failure due to paraquat poisoning?
AB  - INTRODUCTION: Paraquat poisoning can result in dysfunction of multiple organs,
      and pulmonary fibrosis with respiratory failure is the major cause of mortality.
      For terminally ill patients, some life-prolonging treatments can be non
      beneficial treatments (NBT). The objective of this study was to determine if
      intubation is a NBT for patients with respiratory failure due to paraquat
      poisoning. METHODS: The study included 68 patients with respiratory failure due
      to paraquat poisoning. Patients were hospitalized at MacKay Memorial Hospital,
      Taitung Branch, Taiwan, between 2005 to April 2016. Composite outcomes of intra
      hospital mortality, the rate of do-not-resuscitate (DNR) orders, prescribed
      medications, length of stay, and medical costs were recorded and compared between
      the do-not-intubate (DNI) group and endotracheal intubation (EI) group. RESULTS:
      Intra-hospital mortality rate for the entire population was 100%. There were
      significantly more patients with DNR orders in the DNI group (P = 0.007). There
      were no differences in the length of hospital stay. However, patients in DNI
      group had significantly less vasopressor use and more morphine use, shorter time
      in the intensive care unit, and fewer medical costs. CONCLUSION: The procedure of
      intubation in patients with respiratory failure due to paraquat poisoning can be
      considered inappropriate life-prolonging treatment.

PMID- 29590188
TI  - Overview of systematic reviews assessing the evidence for shorter versus longer
      duration antibiotic treatment for bacterial infections in secondary care.
AB  - Our objective was to assess the clinical effectiveness of shorter versus longer
      duration antibiotics for treatment of bacterial infections in adults and children
      in secondary care settings, using the evidence from published systematic reviews.
      We conducted electronic searches in MEDLINE, Embase, Cochrane, and Cinahl. Our
      primary outcome was clinical resolution. The quality of included reviews was
      assessed using the AMSTAR criteria, and the quality of the evidence was rated
      using the GRADE criteria. We included 6 systematic reviews (n = 3,162). Four
      reviews were rated high quality, and two of moderate quality. In adults, there
      was no difference between shorter versus longer duration in clinical resolution
      rates for peritonitis (RR 1.03, 95% CI 0.98 to 1.09, I2 = 0%), ventilator
      associated pneumonia (RR 0.93; 95% CI 0.81 to 1.08, I2 = 24%), or acute
      pyelonephritis and septic UTI (clinical failure: RR 1.00, 95% CI 0.46 to 2.18).
      The quality of the evidence was very low to moderate. In children, there was no
      difference in clinical resolution rates for pneumonia (RR 0.98, 95% CI 0.91 to
      1.04, I2 = 48%), pyelonephritis (RR 0.95, 95% CI 0.88 to 1.04) and confirmed
      bacterial meningitis (RR 1.02, 95% CI 0.93 to 1.11, I2 = 0%). The quality of the
      evidence was low to moderate. In conclusion, there is currently a limited body of
      evidence to clearly assess the clinical benefits of shorter versus longer
      duration antibiotics in secondary care. High quality trials assessing strategies
      to shorten antibiotic treatment duration for bacterial infections in secondary
      care settings should now be a priority.

PMID- 29590190
TI  - MINErosion 3: Using measurements on a tilting flume-rainfall simulator facility
      to predict erosion rates from post-mining landscapes in Central Queensland,
      Australia.
AB  - Open-cut coal mining in Queensland results in the formation of extensive saline
      overburden spoil-piles with steep slopes at the angle of repose (approximately
      75% or 37o). These spoil-piles are generally found in multiple rows, several
      kilometers in length and heights of up to 50 or 60 m above the original
      landscape. They are highly dispersive and erodible. Legislation demands that
      these spoil piles be rehabilitated to minimize on-site and off-site discharges of
      sediment and salt into the surrounding environment. To achieve this, the steep
      slopes must be reduced, stabilized against erosion, covered with topsoil and re
      vegetated. Key design criteria (slope gradient, slope length and vegetation
      cover) are required for the construction of post-mining landscapes that will
      result in acceptable erosion rates. A novel user-friendly hillslope computer
      model MINErosion 3.4 was developed that can accurately predict potential erosion
      rates from field scale hillslopes using parameters measured with a 3m laboratory
      tilting flume-rainfall simulator or using routinely measured soil physical and
      chemical properties. This model links MINErosion 2 with a novel consolidation and
      above ground vegetation cover factors, to the RUSLE and MUSLE equations to
      predict the mean annual and storm event erosion rates. The RUSLE-based prediction
      of the mean annual erosion rates allow minesites to derive the key design
      criteria of slope length, slope gradient and vegetation cover that would lead to
      acceptable erosion rates. The MUSLE-based prediction of storm event erosion rates
      will be useful as input into risk analysis of potential damage from erosion.
      MINErosion 3.4 was validated against erosion measured on 20 m field erosion plots
      established on post-mining landscapes at the Oakey Creek and Curragh coalmines,
      as well as on 120 and 70 m erosion plots on postmining landscapes at Kidston Gold
      Mine.

PMID- 29590189
TI  - Versatile approach for functional analysis of human proteins and efficient stable
      cell line generation using FLP-mediated recombination system.
AB  - Deciphering a function of a given protein requires investigating various
      biological aspects. Usually, the protein of interest is expressed with a fusion
      tag that aids or allows subsequent analyses. Additionally, downregulation or
      inactivation of the studied gene enables functional studies. Development of the
      CRISPR/Cas9 methodology opened many possibilities but in many cases it is
      restricted to non-essential genes. Recombinase-dependent gene integration
      methods, like the Flp-In system, are very good alternatives. The system is widely
      used in different research areas, which calls for the existence of compatible
      vectors and efficient protocols that ensure straightforward DNA cloning and
      generation of stable cell lines. We have created and validated a robust series of
      52 vectors for streamlined generation of stable mammalian cell lines using the
      FLP recombinase-based methodology. Using the sequence-independent DNA cloning
      method all constructs for a given coding-sequence can be made with just three
      universal PCR primers. Our collection allows tetracycline-inducible expression of
      proteins with various tags suitable for protein localization, FRET, bimolecular
      fluorescence complementation (BiFC), protein dynamics studies (FRAP), co
      immunoprecipitation, the RNA tethering assay and cell sorting. Some of the
      vectors contain a bidirectional promoter for concomitant expression of miRNA and
      mRNA, so that a gene can be silenced and its product replaced by a mutated miRNA
      insensitive version. Our toolkit and protocols have allowed us to create more
      than 500 constructs with ease. We demonstrate the efficacy of our vectors by
      creating stable cell lines with various tagged proteins (numatrin, fibrillarin,
      coilin, centrin, THOC5, PCNA). We have analysed transgene expression over time to
      provide a guideline for future experiments and compared the effectiveness of
      commonly used inducers for tetracycline-responsive promoters. As proof of concept
      we examined the role of the exoribonuclease XRN2 in transcription termination by
      RNAseq.

PMID- 29590191
TI  - Gut-bone axis response to dietary replacement of soybean meal with raw low-tannin
      faba bean seeds in broiler chickens.
AB  - It seems that faba bean (FB) seeds could be a good protein-energy component in
      animal feed, but the presence of anti-nutritional substances limits their use as
      a substitute of soybean meal. The aim of the study was to examine the influence
      of different concentrations of raw, low-tannin, FB seeds on the gut-bone axis in
      Ross 308 broilers. One-day old chickens were randomly subjected to one of the 3
      dietary treatments: the control group was fed standard diet based on soybean meal
      and without FB seeds, and two groups were fed 8%/15% and 16%/22% of raw low
      tannin FB seeds in the starter and grower, respectively. On the 35th day,
      hematological and serum biochemical analyses as well histomorphometry of the
      small intestine and liver tissue and bone mechanical tests were performed. The
      diet type had no effect on the body weight gain and feed conversion ratio.
      However, the basal intestinal structures were significantly reduced in birds fed
      the lower concentration of FB. The enlargement of nerve plexuses was dependent on
      the concentration used in the diet and, additionally, on the kind of plexus and
      location in the intestinal tract. The liver was characterized by an increase in
      non-hepatocytes. There was no influence of the low-tannin FB seeds on most of the
      analyzed serum parameters in the 35-day-old broiler chickens, except the
      decreased concentration of total cholesterol and Ca in both experimental groups,
      triglycerides in group I, and P and uric acid in group II. Furthermore, the
      increasing concentration of the dietary low-tannin FB did not influence the
      activities of AspAT (except the group fed the higher amount of FB), ALAT, and
      LDH. The broiler chickens had no visible leg lesions and no problem in the
      locomotor function, but the tibiae were lighter mainly in birds fed the higher
      concentration of FB seeds. Geometric analysis revealed reduction of the cross
      section area and wall thickness, indicating a decline in the bone midshaft, which
      influenced the densitometric parameters and the results of mechanical tests. In
      conclusion, the dietary inclusion of raw low-tannin FB seeds had no negative
      effects on broiler growth, but disturbed the intestine structure and tibia
      characteristics. Therefore, all these negative effects necessitate additional
      examinations before inclusion of raw low-tannin FB seed into poultry diet.

PMID- 29590192
TI  - Landscape connectivity for bobcat (Lynx rufus) and lynx (Lynx canadensis) in the
      Northeastern United States.
AB  - Landscape connectivity is integral to the persistence of metapopulations of wide
      ranging carnivores and other terrestrial species. The objectives of this research
      were to investigate the landscape characteristics essential to use of areas by
      lynx and bobcats in northern New England, map a habitat availability model for
      each species, and explore connectivity across areas of the region likely to
      experience future development pressure. A Mahalanobis distance analysis was
      conducted on location data collected between 2005 and 2010 from 16 bobcats in
      western Vermont and 31 lynx in northern Maine to determine which variables were
      most consistent across all locations for each species using three scales based on
      average 1) local (15 minute) movement, 2) linear distance between daily
      locations, and 3) female home range size. The bobcat model providing the widest
      separation between used locations and random study area locations suggests that
      they cue into landscape features such as edge, availability of cover, and
      development density at different scales. The lynx model with the widest
      separation between random and used locations contained five variables including
      natural habitat, cover, and elevation-all at different scales. Shrub scrub
      habitat-where lynx's preferred prey is most abundant-was represented at the daily
      distance moved scale. Cross validation indicated that outliers had little effect
      on models for either species. A habitat suitability value was calculated for each
      30 m2 pixel across Vermont, New Hampshire, and Maine for each species and used to
      map connectivity between conserved lands within selected areas across the region.
      Projections of future landscape change illustrated potential impacts of
      anthropogenic development on areas lynx and bobcat may use, and indicated where
      connectivity for bobcats and lynx may be lost. These projections provided a guide
      for conservation of landscape permeability for lynx, bobcat, and species relying
      on similar habitats in the region.

PMID- 29590193
TI  - Automated C. elegans embryo alignments reveal brain neuropil position invariance
      despite lax cell body placement.
AB  - The Caenorhabditis elegans cell lineage is nearly invariant. Whether this
      stereotyped cell-division pattern promotes reproducibility in cell
      shapes/positions is not generally known, as manual spatiotemporal cell
      shape/position alignments are labor-intensive, and fully-automated methods are
      not described. Here, we report automated algorithms for spatiotemporal alignments
      of C. elegans embryos from pre-morphogenesis to motor-activity initiation. We use
      sparsely-labeled green-fluorescent nuclei and a pan-nuclear red-fluorescent
      reporter to register consecutive imaging time points and compare embryos. Using
      our method, we monitor early assembly of the nerve-ring (NR) brain neuropil.
      While NR pioneer neurons exhibit reproducible growth kinetics and axon positions,
      cell-body placements are variable. Thus, pioneer-neuron axon locations, but not
      cell-body positions, are under selection. We also show that anterior NR
      displacement in cam-1/ROR Wnt-receptor mutants is not an early NR assembly
      defect. Our results demonstrate the utility of automated spatiotemporal
      alignments of C. elegans embryos, and uncover key principles guiding nervous
      system development in this animal.

PMID- 29590194
TI  - Highly-sensitive detection of Salmonella typhi in clinical blood samples by
      magnetic nanoparticle-based enrichment and in-situ measurement of isothermal
      amplification of nucleic acids.
AB  - Enteric fever continues to be a major cause of mortality and morbidity globally,
      particularly in poor resource settings. Lack of rapid diagnostic assays is a
      major driving factor for the empirical treatment of enteric fever. In this work,
      a rapid and sensitive method 'Miod' 'has been developed. Miod includes a magnetic
      nanoparticle-based enrichment of target bacterial cells, followed by cell lysis
      and loop-mediated isothermal amplification (LAMP) of nucleic acids for signal
      augmentation along with concurrent measurement of signal via an in-situ optical
      detection system. To identify positive/negative enteric fever infections in
      clinical blood samples, the samples were processed using Miod at time = 0 hours
      and time = 4 hours post-incubation in blood culture media. Primers specific for
      the STY2879 gene were used to amplify the nucleic acids isolated from S. typhi
      cells. A limit of detection of 5 CFU/mL was achieved. No cross-reactivity of the
      primers were observed against 106 CFU/mL of common pathogenic bacterial species
      found in blood such as E. coli, P. aeruginosa, S. aureus, A. baumanni, E.
      faecalis, S. Paratyphi A and K. pneumonia. Miod was tested on 28 human clinical
      blood samples. The detection of both pre-and post-four-hours incubation confirmed
      the presence of viable S. typhi cells and allowed clinical correlation of
      infection. The positive and negative samples were successfully detected in less
      than 6 hours with 100% sensitivity and specificity.

PMID- 29590195
TI  - The neurochemistry and morphology of functionally identified corneal polymodal
      nociceptors and cold thermoreceptors.
AB  - It is generally believed that the unencapsulated sensory nerve terminals of
      modality specific C- and Adelta-neurons lack structural specialization. Here we
      determined the morphology of functionally defined polymodal receptors and cold
      thermoreceptors in the guinea pig corneal epithelium. Polymodal receptors and
      cold thermoreceptors were identified by extracellular recording at the surface of
      the corneal epithelium. After marking the recording sites, corneas were processed
      to reveal immunoreactivity for the transient receptor potential channels TRPV1
      (transient receptor potential cation channel, subfamily V, member 1) or TPRM8
      (transient receptor potential cation channel subfamily M member 8). Polymodal
      receptor nerve terminals (n = 6) were TRPV1-immunoreactive and derived from an
      axon that ascended from the sub-basal plexus to the squamous cell layer where it
      branched into fibers that ran parallel to the corneal surface and terminated with
      small bulbar endings (ramifying endings). Cold thermoreceptor nerve terminals
      were TRPM8-immunoreactive (n = 6) and originated from an axon that branched as it
      ascended through the wing cell and squamous cell layers and terminated with large
      bulbar endings (complex endings). These findings indicate that modality specific
      corneal sensory neurons with unencapsulated nerve endings have distinct nerve
      terminal morphologies that are likely to relate to their function.

PMID- 29590196
TI  - Asymptomatic norovirus infection associated with swimming at a tropical beach: A
      prospective cohort study.
AB  - BACKGROUND: Swimming in fecally-contaminated waterbodies can result in
      gastrointestinal infections. However, the pathogenic microorganisms responsible
      are not well understood because sporadic cases of illness are not reported
      completely, exposure information is often not collected, and epidemiology studies
      rely on self-reported symptoms. Noroviruses are considered a likely cause because
      they are found in high densities in sewage, resistant to wastewater treatment and
      survive in the environment. In this study, saliva samples were collected from
      subjects at a beach in Puerto Rico and tested for evidence of norovirus-specific
      IgG responses as an indicator of incident norovirus infection. METHODS: Saliva
      samples were collected from 1298 participants using an oral swab. Samples were
      collected on the day of the beach visit (S1); after 10-12 days (S2); and after
      three weeks (S3). Saliva was tested for IgG responses to GI.1 and GII.4
      noroviruses using a microsphere based multiplex salivary immunoassay.
      Immunoconversion was defined as a four-fold increase in median fluorescence
      intensity (MFI) from S1 to S2 with the S3 sample at least three times above the
      S1 MFI. RESULTS: Thirty-four subjects (2.6%) immunoconverted to GI.1 or GII.4
      norovirus. Swimmers who immersed their head in water had a higher rate of
      immunoconversion (3.4%), compared to either non-swimmers (0.0%, p = 0.003) or
      waders and non-swimmers combined (0.4%, Odds Ratio: 5.07, 95% Confidence
      Interval:1.48-17.00). Immunoconversion was not associated with gastrointestinal
      symptoms. CONCLUSIONS: This is the first study to demonstrate an association
      between swimming at a beach impacted by fecal contamination and asymptomatic
      norovirus infection. The findings implicate recreational water as potentially
      important transmission pathway for norovirus infection.

PMID- 29590197
TI  - Correlation between coronary artery calcification by non-cardiac CT and
      Framingham score in young patients.
AB  - BACKGROUND: Previous studies have established a correlation between coronary
      artery calcification (CAC) measured by ECG-gated chest computed tomography (CT)
      and cardiovascular disease. Recent reports which included asymptomatic patients
      suggest that CAC measured on non-ECG gated CT is similarly associated with
      cardiovascular risk. This study investigates the correlation between the
      Framingham Risk Score (FRS) and an incidental finding of CAC on a non-gated chest
      CT performed for non-cardiac indications in young and seemingly healthy adults.
      METHODS: A cross-sectional study that included 162 CT scans performed in young
      patients aged 18-50 years old for non-cardiac indications in our institution was
      conducted. CAC score (CACS) was calculated using the Agatston method. FRS was
      calculated and compared to the CACS using three different approaches. The
      correlations between the CACS and several specific factors (i.e. age, body mass
      index, smoking, statins, etc.), were also evaluated. RESULTS: Mean age of
      patients was 36.43 year old and 105 (64.8%) were male. We found a significant
      positive correlation between the CACS and the FRS in all three approaches
      (p<0.05). Increased age, smoking and statin use were the only individual factors
      clearly associated with an increase in CACS (p = 0.002, p = 0.045 and p = 0.009,
      respectively). CONCLUSION: This is the first report indicating that incidental
      CACS identified in non-gated MDCT is also associated with cardiovascular risk
      evaluated by FRS in a young population. Our findings suggest that young
      asymptomatic individuals with incidental CAC should be seriously evaluated for
      cardiovascular risk factors despite presumption of belonging to a low
      cardiovascular risk category.

PMID- 29590198
TI  - Verrucomicrobia are prevalent in north-temperate freshwater lakes and display
      class-level preferences between lake habitats.
AB  - The bacterial phylum Verrucomicrobia was formally described two decades ago and
      originally believed to be a minor member of many ecosystems; however, it is now
      recognized as ubiquitous and abundant in both soil and aquatic systems.
      Nevertheless, knowledge of the drivers of its relative abundance and within
      phylum habitat preferences remains sparse, especially in lake systems. Here, we
      documented the distribution of Verrucomicrobia in 12 inland lakes in Southeastern
      Michigan, a Laurentian Great Lake (Lake Michigan), and a freshwater estuary,
      which span a gradient in lake sizes, depths, residence times, and trophic states.
      A wide range of physical and geochemical parameters was covered by sampling
      seasonally from the surface and bottom of each lake, and by separating samples
      into particle-associated and free-living fractions. On average, Verrucomicrobia
      was the 4th most abundant phylum (range 1.7-41.7%). Fraction, season, station,
      and depth explained up to 70% of the variance in Verrucomicrobia community
      composition and preference for these habitats was phylogenetically conserved at
      the class-level. When relative abundance was linearly modeled against
      environmental data, Verrucomicrobia and non-Verrucomicrobia bacterial community
      composition correlated to similar quantitative environmental parameters, although
      there were lake system-dependent differences and > 55% of the variance remained
      unexplained. A majority of the phylum exhibited preference for the particle
      associated fraction and two classes (Opitutae and Verrucomicrobiae) were
      identified to be more abundant during the spring season. This study highlights
      the high relative abundance of Verrucomicrobia in north temperate lake systems
      and expands insights into drivers of within-phylum habitat preferences of the
      Verrucomicrobia.

PMID- 29590199
TI  - The urine albumin-creatinine ratio is a predictor for incident long-term care in
      a general population.
AB  - BACKGROUND: Several types of cardiovascular diseases (CVDs) impair the physical
      and mental status. The purpose of this study was to assess the predictive ability
      of several cardiovascular biomarkers for identifying the incidence of disability
      as future recipients of public long-term care (LTC) service. METHODS: The
      subjects of this study were community-dwelling elderly individuals >= 65 years of
      age without a history of CVD (n = 5,755; mean age, 71 years). The endpoint of
      this study was official certification as a recipient of LTC. The cohort was
      divided into quartiles (Qs) based on the levels of three CVD biomarkers: the
      urinary albumin-creatinine ratio (UACR), plasma B-type natriuretic peptide
      concentration (BNP), and serum high-sensitivity C-reactive protein concentration
      (hsCRP). A time-dependent Cox proportional hazard model was used to determine the
      multi-adjusted relative hazard ratios (HRs) for incident LTC among the quartiles
      of each biomarker. RESULTS: During the follow-up (mean 5.6 years), 710 subjects
      were authorized as recipients of LTC. The HR was only significantly increased in
      the higher Qs of UACR (Q3, p < 0.01; Q4, p < 0.001). However, other biomarkers
      were not significantly associated with the endpoint. The risk predictive
      performance for the incidence of LTC as evaluated by an essential model (i.e. age
      and sex-adjusted) was significantly improved by incorporating the UACR (net
      reclassification improvement = 0.084, p < 0.01; integrated discrimination
      improvement = 0.0018, p < 0.01). CONCLUSIONS: These results suggest that an
      increased UACR is useful for predicting physical and cognitive dysfunction in an
      elderly general population.

PMID- 29590200
TI  - Retrospective harm benefit analysis of pre-clinical animal research for six
      treatment interventions.
AB  - BACKGROUND: The harm benefit analysis (HBA) is the cornerstone of animal research
      regulation and is considered to be a key ethical safeguard for animals. The HBA
      involves weighing the anticipated benefits of animal research against its
      predicted harms to animals but there are doubts about how objective and
      accountable this process is. OBJECTIVES: i. To explore the harms to animals
      involved in pre-clinical animal studies and to assess these against the benefits
      for humans accruing from these studies; ii. To test the feasibility of conducting
      this type of retrospective HBA. METHODS: Data on harms were systematically
      extracted from a sample of pre-clinical animal studies whose clinical relevance
      had already been investigated by comparing systematic reviews of the animal
      studies with systematic reviews of human studies for the same interventions
      (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis,
      corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids
      for neonatal respiratory distress and thrombolytics for stroke). Clinical
      relevance was also explored in terms of current clinical practice. Harms were
      categorised for severity using an expert panel. The quality of the research and
      its impact were considered. Bateson's Cube was used to conduct the HBA. RESULTS:
      The most common assessment of animal harms by the expert panel was 'severe'.
      Reported use of analgesia was rare and some animals (including most neonates)
      endured significant procedures with no, or only light, anaesthesia reported. Some
      animals suffered iatrogenic harms. Many were kept alive for long periods post
      experimentally but only 1% of studies reported post-operative care. A third of
      studies reported that some animals died prior to endpoints. All the studies were
      of poor quality. Having weighed the actual harms to animals against the actual
      clinical benefits accruing from these studies, and taking into account the
      quality of the research and its impact, less than 7% of the studies were
      permissible according to Bateson's Cube: only the moderate bisphosphonate studies
      appeared to minimise harms to animals whilst being associated with benefit for
      humans. CONCLUSIONS: This is the first time the accountability of the HBA has
      been systematically explored across a range of pre-clinical animal studies. The
      regulatory systems in place when these studies were conducted failed to safeguard
      animals from severe suffering or to ensure that only beneficial, scientifically
      rigorous research was conducted. Our findings indicate a pressing need to: i.
      review regulations, particularly those that permit animals to suffer severe
      harms; ii. reform the processes of prospectively assessing pre-clinical animal
      studies to make them fit for purpose; and iii. systematically evaluate the
      benefits of pre-clinical animal research to permit a more realistic assessment of
      its likely future benefits.

PMID- 29590201
TI  - Using mating-type loci to improve taxonomy of the Tuber indicum complex, and
      discovery of a new species, T. longispinosum.
AB  - Black truffles that morphologically resemble Tuber indicum have been known to
      occur in Japan since 1979. Our previous studies showed that there are two
      phylotypes of these truffles, both of which fell into the T. indicum complex
      (hereinafter "Tuber sp. 6" and "Tuber sp. 7"). However, their taxonomic treatment
      is still unclear. In this study, we conducted morphological and phylogenetic
      analyses for a total of 52 specimens from Japan (16 Tuber sp. 6 and 13 Tuber sp.
      7), China (10 T. himalayense and 8 T. indicum), and Taiwan (5 T. formosanum). We
      compared ascospore ornamentation, size, distribution of asci with average number
      of spores per ascus, spine size and shape of the Japanese specimens with their
      allied taxa. For phylogenetic analysis, we sequenced two mating loci (MAT1-1-1
      and MAT1-2-1) and three commonly used loci (ITS, beta-tubulin, and TEF1-alpha).
      Three distinct lineages were recognized by phylogenetic analyses based on the
      sequences of the two mating-related loci and three independent loci. The Tuber
      sp. 6 sequences clustered with those of T. himalayense and T. formosanum, and
      there was no clear difference in morphology among them. Tuber sp. 7 formed a
      distinct lineage in each phylogram. The specimens tended to have five-spored asci
      more frequently than other allied species and could be characterized as having
      ascospore ornamentation with longer spines and narrower spine bases. We therefore
      described Tuber sp. 7 as a new species (T. longispinosum), and treat Tuber sp. 6
      and T. formosanum as synonyms of T. himalayense.

PMID- 29590202
TI  - Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics.
AB  - Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and
      during transmission between vertebrate hosts and mosquito vectors is critical for
      a thorough understanding of viral transmission, pathogenesis, immune evasion, and
      potential reservoir establishment. Within-host viral diversity in ZIKV infection
      is low, which makes it difficult to evaluate infection dynamics. To overcome this
      biological hurdle, we constructed a molecularly barcoded ZIKV. This virus stock
      consists of a "synthetic swarm" whose members are genetically identical except
      for a run of eight consecutive degenerate codons, which creates approximately
      64,000 theoretical nucleotide combinations that all encode the same amino acids.
      Deep sequencing this region of the ZIKV genome enables counting of individual
      barcodes to quantify the number and relative proportions of viral lineages
      present within a host. Here we used these molecularly barcoded ZIKV variants to
      study the dynamics of ZIKV infection in pregnant and non-pregnant macaques as
      well as during mosquito infection/transmission. The barcoded virus had no
      discernible fitness defects in vivo, and the proportions of individual barcoded
      virus templates remained stable throughout the duration of acute plasma viremia.
      ZIKV RNA also was detected in maternal plasma from a pregnant animal infected
      with barcoded virus for 67 days. The complexity of the virus population declined
      precipitously 8 days following infection of the dam, consistent with the timing
      of typical resolution of ZIKV in non-pregnant macaques and remained low for the
      subsequent duration of viremia. Our approach showed that synthetic swarm viruses
      can be used to probe the composition of ZIKV populations over time in vivo to
      understand vertical transmission, persistent reservoirs, bottlenecks, and
      evolutionary dynamics.

PMID- 29590204
TI  - Can sign language make you better at hand processing?
AB  - The languages developed by deaf communities are unique for using visual signs
      produced by the hand. In the present study, we explored the cognitive effects of
      employing the hand as articulator. We focused on the arbitrariness of the form
      meaning relationship-a fundamental feature of natural languages-and asked whether
      sign languages change the processing of arbitrary non-linguistic stimulus
      response (S-R) associations involving the hand. This was tested using the Simon
      effect, which specifically requires such type of associations. Differences
      between signers and speakers (non-signers) only appeared in the Simon task when
      hand stimuli were shown. Response-time analyses revealed that the distinctiveness
      of signers' responses derived from an increased ability to process memory traces
      of arbitrary S-R pairs related to the hand. These results shed light on the
      interplay between language and cognition as well as on the effects of sign
      language acquisition.

PMID- 29590203
TI  - Reprogramming of the estrogen responsive transcriptome contributes to tamoxifen
      dependent protection against tumorigenesis in the p53 null mammary epithelial
      cells.
AB  - The tumor suppressor gene p53 is frequently mutated in human breast cancer and is
      a marker for poor prognosis and resistance to chemotherapy. Transplantation of
      p53 null mouse mammary epithelium into syngeneic wild-type mice leads to normal
      mammary gland development followed by spontaneous mammary tumors that
      recapitulate many of the phenotypic, molecular and genetic features of human
      breast cancer. Transient exposure of p53 null mice to the anti-estrogen,
      tamoxifen leads to sustained and robust protection against tumor development.
      However the mechanism underlying this anti-tumor activity remains poorly
      understood. Here we demonstrate that transient exposure to tamoxifen leads to a
      reduction in mammary ductal side-branching and epithelial cell proliferation
      after tamoxifen withdrawal. Global gene expression analysis showed that transient
      tamoxifen exposure leads to persistent changes in the expression of a subset of
      estrogen regulated gene signatures in mammary epithelial cells (MECs). Among
      these was the protein tyrosine phosphatase, non-receptor type 5 (Ptpn5). We show
      that Ptpn5 is a novel tamoxifen regulated target gene which is upregulated in
      MECs after transient tamoxifen exposure and displays tumor suppressor activity in
      human breast cancer cells. Further, PTPN5 expression is strongly associated with
      good clinical outcome in tamoxifen treated human breast cancer patients
      suggesting that PTPN5 may represent a novel biomarker of tamoxifen response in
      human breast cancer.

PMID- 29590205
TI  - A Middle Palaeolithic wooden digging stick from Aranbaltza III, Spain.
AB  - Aranbaltza is an archaeological complex formed by at least three open-air sites.
      Between 2014 and 2015 a test excavation carried out in Aranbaltza III revealed
      the presence of a sand and clay sedimentary sequence formed in floodplain
      environments, within which six sedimentary units have been identified. This
      sequence was formed between 137-50 ka, and includes several archaeological
      horizons, attesting to the long-term presence of Neanderthal communities in this
      area. One of these horizons, corresponding with Unit 4, yielded two wooden tools.
      One of these tools is a beveled pointed tool that was shaped through a complex
      operational sequence involving branch shaping, bark peeling, twig removal,
      shaping, polishing, thermal exposition and chopping. A use-wear analysis of the
      tool shows it to have traces related with digging soil so it has been interpreted
      as representing a digging stick. This is the first time such a tool has been
      identified in a European Late Middle Palaeolithic context; it also represents one
      of the first well-preserved Middle Palaeolithic wooden tool found in southern
      Europe. This artefact represents one of the few examples available of wooden tool
      preservation for the European Palaeolithic, allowing us to further explore the
      role wooden technologies played in Neanderthal communities.

PMID- 29590206
TI  - Worldwide increased prevalence of human adenovirus type 3 (HAdV-3) respiratory
      infections is well correlated with heterogeneous hypervariable regions (HVRs) of
      hexon.
AB  - Human adenovirus type 3 (HAdV-3) respiratory infections occurs worldwide in both
      children and adults, leading to severe morbidity and mortality, particularly in
      the paediatric age group and especially in neonates. During HAdV infection,
      neutralizing antibodies are formed against the epitopes located in the hyper
      variable regions (HVRs) of the hexon protein. These neutralizing antibodies
      provide protection against reinfection by viruses of the same type. Therefore it
      is reasonable to speculate that variations of HAdV-3 in the HVRs could impair the
      immunity acquired by previous infection with a different strain with variation in
      its HVRs. HAdV-3 has recently become the major agent of acute respiratory
      infection worldwide, being responsible for 15% to 87% of all adenoviral
      respiratory infections. However, despite the increased prevalence of HAdV-3 as
      respiratory pathogen, the diversity of hexon proteins in circulating strains
      remains unexplored. This study was designed to explore the variation in HVRs of
      hexon among globally distributed strains of HAdV-3 as well as to discover
      possible relationship among them, thus possibly shedding light on the cause for
      the increased prevalence of HAdV-3. In this study, for the first time we analysed
      the hexon proteins of all 248 available strains of HAdV-3 from the NCBI database
      and compared them with those of the HAdV-3 prototype (GB stain). We found that
      the HVRs of HAdV-3 strains circulating worldwide were highly heterogeneous and
      have been mutating continuously since -their original isolation. Based on their
      immense heterogeneity, the strains can be categorized into 25 hexon variants (3Hv
      1 to 3Hv-25), 4 of which (3Hv-1 to 3Hv-4) comprises 80% of the strains. This
      heterogeneity may explain why HAdV-3 has become the most prevalent HAdVs type
      worldwide. The heterogeneity of hexon proteins also shows that the development of
      a vaccine against HAdV-3 might be challenging. The data on hexon variants
      provided here may be useful for the future epidemiological study of HAdV-3
      infection.

PMID- 29590208
TI  - Rome in its setting. Post-glacial aggradation history of the Tiber River alluvial
      deposits and tectonic origin of the Tiber Island.
AB  - The Tiber valley is a prominent feature in the landscape of ancient Rome and an
      important element for understanding its urban development. However, little is
      known about the city's original setting. Our research provides new data on the
      Holocene sedimentary history and human-environment interactions in the Forum
      Boarium, the location of the earliest harbor of the city. Since the Last Glacial
      Maximum, when the fluvial valley was incised to a depth of tens of meters below
      the present sea level, 14C and ceramic ages coupled with paleomagnetic analysis
      show the occurrence of three distinct aggradational phases until the
      establishment of a relatively stable alluvial plain at 6-8 m a.s.l. during the
      late 3rd century BCE. Moreover, we report evidence of a sudden and anomalous
      increase in sedimentation rate around 2600 yr BP, leading to the deposition of a
      4-6m thick package of alluvial deposits in approximately one century. We discuss
      this datum in the light of possible tectonic activity along a morpho-structural
      lineament, revealed by the digital elevation model of this area, crossing the
      Forum Boarium and aligned with the Tiber Island. We formulate the hypothesis that
      fault displacement along this structural lineament may be responsible for the
      sudden collapse of the investigated area, which provided new space for the
      observed unusually large accumulation of sediments. We also posit that, as a
      consequence of the diversion of the Tiber course and the loss in capacity of
      transport by the river, this faulting activity triggered the origin of the Tiber
      Island.

PMID- 29590207
TI  - Dynamics of tandemly repeated DNA sequences during evolution of diploid and
      tetraploid botiid loaches (Teleostei: Cobitoidea: Botiidae).
AB  - Polyploidization has played an important role in the evolution of vertebrates,
      particularly at the base of Teleostei-an enormously successful ray-finned fish
      group with additional genome doublings on lower taxonomic levels. The
      investigation of post-polyploid genome dynamics might provide important clues
      about the evolution and ecology of respective species and can help to decipher
      the role of polyploidy per se on speciation. Few studies have attempted to
      investigate the dynamics of repetitive DNA sequences in the post-polyploid genome
      using molecular cytogenetic tools in fishes, though recent efforts demonstrated
      their usefulness. The demonstrably monophyletic freshwater loach family Botiidae,
      branching to evolutionary diploid and tetraploid lineages separated >25 Mya,
      offers a suited model group for comparing the long-term repetitive DNA evolution.
      For this, we integrated phylogenetic analyses with cytogenetical survey involving
      Giemsa- and Chromomycin A3 (CMA3)/DAPI stainings and fluorescence in situ
      hybridization with 5S/45S rDNA, U2 snDNA and telomeric probes in representative
      sample of 12 botiid species. The karyotypes of all diploids were composed of 2n =
      50 chromosomes, while majority of tetraploids had 2n = 4x = 100, with only subtle
      interspecific karyotype differences. The exceptional karyotype of Botia dario (2n
      = 4x = 96) suggested centric fusions behind the 2n reduction. Variable patterns
      of FISH signals revealed cases of intraspecific polymorphisms, rDNA
      amplification, variable degree of correspondence with CMA3+ sites and almost no
      phylogenetic signal. In tetraploids, either additivity or loci gain/loss was
      recorded. Despite absence of classical interstitial telomeric sites, large blocks
      of interspersed rDNA/telomeric regions were found in diploids only. We uncovered
      different molecular drives of studied repetitive DNA classes within botiid
      genomes as well as the advanced stage of the re-diploidization process in
      tetraploids. Our results may contribute to link genomic approach with molecular
      cytogenetic analyses in addressing the origin and mechanism of this
      polyploidization event.

PMID- 29590209
TI  - Patients with atrial fibrillation and permanent pacemaker: Temporal changes in
      patient characteristics and pharmacotherapy.
AB  - BACKGROUND: The management of patients with non-valvular atrial fibrillation
      (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the
      last decade, but it is unknown how these changes have affected patients with NVAF
      with a permanent pacemaker (PPM). METHODS: Through Danish nationwide registries,
      patients with NVAF and a PPM were identified from 2001 to 2012. Changes in
      concomitant pharmacotherapy and comorbidities were tested using the Cochran
      Armitage trend test and linear regression. Patients with NVAF were identified to
      calculate the proportional amount of PPM implants. RESULTS: A total of 12,231
      NVAF patients with a PPM were included in the study, 55.6% of which were men.
      Median age was 78 years (interquartile range 70-84). From 2001 to 2012, the
      number of NVAF patients with a PPM increased from 850 to 1344, while the number
      of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount
      of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall
      45.9% had atrial fibrillation (AF) duration less than one year and the proportion
      declined from 55.5% to 42.4% (p <0.001). Diabetes mellitus increased from 7.2% to
      16.8% (p <0.001). Heart failure (HF) decreased from 36.7% to 29.3% (p = 0.010)
      and ischemic heart disease (IHD) decreased from 32.4% to 26.1% (p <0.001). Beta
      blocker use increased from 38.1% to 58.0% (p <0.001), while digoxin and anti
      arrhythmic drug use decreased over time. CONCLUSION: From 2001 to 2012, the
      absolute number of NVAF patients with a PPM increased while the proportional
      amount decreased. The number of NVAF patients receiving a PPM within one year of
      AF diagnosis decreased. The prevalence of DM increased, while the prevalence of
      HF and IHD was high but decreasing. The use of beta-blockers increased markedly,
      while use of digoxin and anti-arrhythmic drugs decreased over time.

PMID- 29590210
TI  - Correction: Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T
      Cells Conveys the Ability to Suppress SIV Replication.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0023703.].

PMID- 29590211
TI  - Income-based inequalities in caregiving time and depressive symptoms among older
      family caregivers under the Japanese long-term care insurance system: A cross
      sectional analysis.
AB  - AIM: Long-term care systems may alleviate caregiver burdens, particularly for
      those with fewer resources. However, it remains unclear whether socioeconomic
      disparity in caregiver burdens exists under a public, universal long-term care
      insurance (LTCI) system. This study examined income-based inequalities in
      caregiving time and depressive symptoms in Japanese older family caregivers. We
      further compared inequality in depressive symptoms with that of non-caregivers to
      evaluate whether family caregiving exacerbates this disparity. METHODS: Data were
      obtained from a cross-sectional, nationwide survey conducted by the Japan
      Gerontological Evaluation Study in 2013. Participants were functionally
      independent older adults aged >=65 years (N = 21,584). Depressive symptoms were
      assessed using the Geriatrics Depression Scale (GDS); caregiving hours per week,
      household income, and other covariates were also assessed. RESULTS: Family
      caregivers occupied 8.3% of the total. A Poisson regression model revealed that
      caregivers in lower income groups (compared to those in the highest) were 1.32 to
      1.95 and 1.63 to 2.68 times more likely to engage in >=36 and >=72 hours/week of
      caregiving, respectively. As for the GDS (>=5), an excess risk was found in the
      caregivers in lower (compared to higher) income groups (adjusted prevalence
      ratio: 1.57-3.10). However, an interaction effect of income by caregiving role
      indicated no significant difference in inequality between caregivers and non
      caregivers (p = .603). The excess risk for GDS (>=5) in the caregivers compared
      to non-caregivers was observed across income groups. CONCLUSIONS: Our findings
      revealed a possible disparity in family caregivers under the public LTCI system.
      Further studies should examine factors associated with longer caregiving hours in
      lower income households. Our findings also suggest the necessity for more efforts
      to alleviate depressive symptoms in family caregivers under the LTCI system
      regardless of income level, rather than exclusively supporting those with a low
      income.

PMID- 29590212
TI  - Cardiorespiratory fitness and the metabolic syndrome: Roles of inflammation and
      abdominal obesity.
AB  - OBJECTIVE: Individuals with metabolic syndrome have increased risk of type 2
      diabetes and cardiovascular disease. We aimed to test the hypothesis that a high
      level of cardiorespiratory fitness (CR-fitness), counteracts accumulation of
      visceral fat, decreases inflammation and lowers risk factors of the metabolic
      syndrome. METHOD: The study sample included 1,293 Danes (age 49-52 years) who
      from 2009 to 2011 participated in the Copenhagen Aging and Midlife Biobank,
      including a questionnaire, physical tests, and blood samples. Multiple linear
      regression models were performed with CR-fitness as exposure and plasma levels of
      cytokines and high sensitive C-reactive protein as outcomes and measures of
      abdominal obesity were added to test if they explained the potential association.
      Similarly, multiple linear regression models were performed with CR-fitness as
      exposure and factors of the metabolic syndrome as outcomes and the potential
      explanation by inflammatory biomarkers were tested. All models were adjusted for
      the effect of age, sex, smoking, alcohol consumption, socio-economic status, and
      acute inflammatory events within the preceding two weeks. RESULTS: CR-fitness was
      inversely associated with high sensitive C-reactive protein, Interleukin (IL)-6,
      and IL-18, and directly associated with the anti-inflammatory cytokine IL-10, but
      not associated with tumor necrosis factor alpha, interferon gamma or IL-1beta.
      Abdominal obesity could partly explain the significant associations. Moreover, CR
      fitness was inversely associated with an overall metabolic syndrome score, as
      well as triglycerides, glycated haemoglobin A1c, systolic blood pressure,
      diastolic blood pressure and directly associated with high-density lipoprotein.
      Single inflammatory biomarkers and a combined inflammatory score partly explained
      these associations. CONCLUSION: Data suggest that CR-fitness has anti
      inflammatory effects that are partly explained by a reduction in abdominal
      obesity and a decrease in the metabolic syndrome risk profile. The overall
      inflammatory load was mainly driven by high sensitive C-reactive protein and IL
      6.

PMID- 29590214
TI  - Correction: Patterns of sedentary behavior in overweight and moderately obese
      users of the Catalan primary-health care system.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190750.].

PMID- 29590213
TI  - Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats.
AB  - Vagus nerve stimulation (VNS) is an approved therapy for treatment of epilepsy
      and depression. While also shown to be promising in several preclinical and
      clinical studies to treat cardiovascular diseases, optimal therapeutic
      stimulation paradigms are still under investigation. Traditionally, parameters
      such as frequency, current, and duty cycle are used to adjust the efficacy of VNS
      therapy. This study explored the effect of novel stochastic VNS (S-VNS) on acute
      heart rate (HR) dynamics. The effect of S-VNS was evaluated in Sprague Dawley
      rats by comparing the acute HR and HR variability (HRV) responses to standard,
      periodic VNS (P-VNS) across different frequencies (FREQs, 10-30 Hz). Our results
      demonstrate that both S-VNS and P-VNS produced negative chronotropic effects in a
      FREQ-dependent manner with S-VNS inducing a significantly smaller drop in HR at
      10 Hz and 20 Hz compared to P-VNS (p<0.05). S-VNS demonstrated a FREQ-dependent
      drop in the SD1/SD2 ratio, a measure of HRV, which was absent in P-VNS,
      suggesting that S-VNS may acutely modulate the nonlinear relationship between
      short- and long-term HRV. In conclusion, S-VNS is a novel stimulation procedure
      that may provide different physiological outcomes from standard P-VNS, as
      indicated by our analysis of HR dynamics. Our study provides a rationale for
      further detailed investigations into the therapeutic potential of S-VNS as a
      novel neuromodulation technique.

PMID- 29590216
TI  - Perception of the importance of chemistry research papers and comparison to
      citation rates.
AB  - Chemistry researchers are frequently evaluated on the perceived significance of
      their work with the citation count as the most commonly-used metric for gauging
      this property. Recent studies have called for a broader evaluation of
      significance that includes more nuanced bibliometrics as well as altmetrics to
      more completely evaluate scientific research. To better understand the
      relationship between metrics and peer judgements of significance in chemistry, we
      have conducted a survey of chemists to investigate their perceptions of
      previously published research. Focusing on a specific issue of the Journal of the
      American Chemical Society published in 2003, respondents were asked to select
      which articles they thought best matched importance and significance given
      several contexts: highest number of citations, most significant (subjectively
      defined), most likely to share among chemists, and most likely to share with a
      broader audience. The answers to the survey can be summed up in several
      observations. The ability of respondents to predict the citation counts of
      established research is markedly lower than the ability of those counts to be
      predicted by the h-index of the corresponding author of each article. This
      observation is conserved even when only considering responses from chemists whose
      expertise falls within the subdiscipline that best describes the work performed
      in an article. Respondents view both cited papers and significant papers
      differently than papers that should be shared with chemists. We conclude from our
      results that peer judgements of importance and significance differ from metrics
      based measurements, and that chemists should work with bibliometricians to
      develop metrics that better capture the nuance of opinions on the importance of a
      given piece of research.

PMID- 29590215
TI  - The draft genome of Kipferlia bialata reveals reductive genome evolution in
      fornicate parasites.
AB  - The fornicata (fornicates) is a eukaryotic group known to consist of free-living
      and parasitic organisms. Genome datasets of two model fornicate parasites Giardia
      intestinalis and Spironucleus salmonicida are well annotated, so far. The nuclear
      genomes of G. intestinalis assemblages and S. salmonicida are small in terms of
      the genome size and simple in genome structure. However, an ancestral genomic
      structure and gene contents, from which genomes of the fornicate parasites have
      evolved, remains to be clarified. In order to understand genome evolution in
      fornicates, here, we present the draft genome sequence of a free-living
      fornicate, Kipferlia bialata, the divergence of which is earlier than those of
      the fornicate parasites, and compare it to the genomes of G. intestinalis and S.
      salmonicida. Our data show that the number of protein genes and introns in K.
      bialata genome are the most abundant in the genomes of three fornicates,
      reflecting an ancestral state of fornicate genome evolution. Evasion mechanisms
      of host immunity found in G. intestinalis and S. salmonicida are absent in the K.
      bialata genome, suggesting that the two parasites acquired the complex membrane
      surface proteins on the line leading to the common ancestor of G. intestinalis
      and S. salmonicida after the divergence from K. bialata. Furthermore, the
      mitochondrion related organelles (MROs) of K. bialata possess more complex suites
      of metabolic pathways than those in Giardia and in Spironucleus. In sum, our
      results unveil the process of reductive evolution which shaped the current
      genomes in two model fornicate parasites G. intestinalis and S. salmonicida.

PMID- 29590217
TI  - BBS1 is involved in retrograde trafficking of ciliary GPCRs in the context of the
      BBSome complex.
AB  - Protein trafficking within cilia is mediated by the intraflagellar transport
      (IFT) machinery composed of large protein complexes. The BBSome consists of eight
      BBS proteins encoded by causative genes of Bardet-Biedl syndrome (BBS), and has
      been implicated in the trafficking of ciliary membrane proteins, including G
      protein-coupled receptors (GPCRs), by connecting the IFT machinery to cargo
      GPCRs. Membrane recruitment of the BBSome to promote cargo trafficking has been
      proposed to be regulated by the Arf-like small GTPase ARL6/BBS3, through its
      interaction with the BBS1 subunit of the BBSome. We here investigated how the
      BBSome core subcomplex composed of BBS1, BBS2, BBS7, and BBS9 assembles and
      interacts with ARL6, and found that the ARL6-BBS1 interaction is reinforced by
      BBS9. BBS1-knockout (KO) cells showed defects in the ciliary entry of other
      BBSome subunits and ARL6, and in ciliary retrograde trafficking and the export of
      the GPCRs, Smoothened and GPR161. The trafficking defect of these GPCRs was
      rescued by the exogenous expression of wild-type BBS1, but not by its mutant
      lacking BBS9-binding ability. Our data thus indicate that the intact BBSome is
      required for retrograde trafficking of GPCRs out of cilia.

PMID- 29590218
TI  - Interaction of HuDA and PABP at 5'UTR of mouse insulin2 regulates insulin
      biosynthesis.
AB  - Understanding the regulation of insulin biosynthesis is important as it plays a
      central role in glucose metabolism. The mouse insulin gene2 (Ins2) has two splice
      variants; long (Ins2L) and short (Ins2S), that differ only in their 5'UTR
      sequence and Ins2S is the major transcript which translate more efficiently as
      compared to Ins2L. Here, we show that cellular factors bind preferentially to the
      Ins2L 5'UTR, and that PABP and HuD can bind to Ins2 splice variants and regulate
      its translation. In vitro binding assay with insulin 5'UTR and different HuD
      isoforms indicate that the 'N' terminal region of HuD is important for RNA
      binding and insulin translation repression. Using reporter assay we showed that
      specifically full-length HuD A isoform represses translation of reporter
      containing insulin 5'UTR. We further show that PABP and HuD interact with each
      other in RNA-dependent manner and this interaction is affected by glucose and PDI
      (5'UTR associated translation activator). These results suggest that PABP
      interacts with HuD in basal glucose conditions making translation inhibitory
      complex, however upon glucose stimulation this association is affected and PABP
      is acted upon by PDI resulting in stimulation of insulin translation. Together,
      our findings snapshot the mechanism of post-transcriptional regulation of insulin
      biosynthesis.

PMID- 29590219
TI  - Personalized survival predictions via Trees of Predictors: An application to
      cardiac transplantation.
AB  - BACKGROUND: Risk prediction is crucial in many areas of medical practice, such as
      cardiac transplantation, but existing clinical risk-scoring methods have
      suboptimal performance. We develop a novel risk prediction algorithm and test its
      performance on the database of all patients who were registered for cardiac
      transplantation in the United States during 1985-2015. METHODS AND FINDINGS: We
      develop a new, interpretable, methodology (ToPs: Trees of Predictors) built on
      the principle that specific predictive (survival) models should be used for
      specific clusters within the patient population. ToPs discovers these specific
      clusters and the specific predictive model that performs best for each cluster.
      In comparison with existing clinical risk scoring methods and state-of-the-art
      machine learning methods, our method provides significant improvements in
      survival predictions, both post- and pre-cardiac transplantation. For instance:
      in terms of 3-month survival post-transplantation, our method achieves AUC of
      0.660; the best clinical risk scoring method (RSS) achieves 0.587. In terms of 3
      year survival/mortality predictions post-transplantation (in comparison to RSS),
      holding specificity at 80.0%, our algorithm correctly predicts survival for 2,442
      (14.0%) more patients (of 17,441 who actually survived); holding sensitivity at
      80.0%, our algorithm correctly predicts mortality for 694 (13.0%) more patients
      (of 5,339 who did not survive). ToPs achieves similar improvements for other time
      horizons and for predictions pre-transplantation. ToPs discovers the most
      relevant features (covariates), uses available features to best advantage, and
      can adapt to changes in clinical practice. CONCLUSIONS: We show that, in
      comparison with existing clinical risk-scoring methods and other machine learning
      methods, ToPs significantly improves survival predictions both post- and pre
      cardiac transplantation. ToPs provides a more accurate, personalized approach to
      survival prediction that can benefit patients, clinicians, and policymakers in
      making clinical decisions and setting clinical policy. Because survival
      prediction is widely used in clinical decision-making across diseases and
      clinical specialties, the implications of our methods are far-reaching.

PMID- 29590222
TI  - Immediate Implant Placement in Single-Tooth Molar Extraction Sockets: A 1- to 6
      Year Retrospective Clinical Study.
AB  - The aim of this study was to investigate the survival rate of implants
      immediately placed in fresh extraction sockets of molars in the maxilla and
      mandible with a single-stage procedure. A total of 102 patients were treated, and
      107 implants (53 in the maxilla and 54 in the mandible) were placed in a fresh
      molar extraction socket and connected to a healing abutment. After a mean follow
      up of 3 years (range: 1 to 6 years) 1 implant failed, for a cumulative success
      rate of 99.06% (98.11% for the mandible and 100% for the maxilla). The results of
      this study support placement of an implant immediately after the extraction of a
      molar, applying a single-stage procedure.

PMID- 29590220
TI  - A fatty acid analogue targeting mitochondria exerts a plasma triacylglycerol
      lowering effect in rats with impaired carnitine biosynthesis.
AB  - L-carnitine is important for the catabolism of long-chain fatty acids in the
      mitochondria. We investigated how the triacylglycerol (TAG)-lowering drug 2
      (tridec-12-yn-1-ylthio)acetic acid (1-triple TTA) influenced lipid metabolism in
      carnitine-depleted, 3-(2,2,2-trimethylhydrazinium)propionate dehydrate
      (Mildronate; meldonium)-treated male Wistar rats. As indicated, carnitine
      biosynthesis was impaired by Mildronate. However, TAG levels of both plasma and
      liver were decreased by 1-triple TTA in Mildronate-treated animals. This was
      accompanied by increased gene expression of proteins involved in mitochondrial
      activity and proliferation and reduced mRNA levels of Dgat2, ApoB and ApoCIII in
      liver. The hepatic energy state was reduced in the group of Mildronate and 1
      triple TTA as reflected by increased AMP/ATP ratio, reduced energy charge and
      induced gene expression of uncoupling proteins 2 and 3. The increase in
      mitochondrial fatty acid oxidation was observed despite low plasma carnitine
      levels, and was linked to strongly induced gene expression of carnitine
      acetyltransferase, translocase and carnitine transporter, suggesting an efficient
      carnitine turnover. The present data suggest that the plasma TAG-lowering effect
      of 1-triple TTA in Mildronate-treated rats is not only due to increased
      mitochondrial fatty acid oxidation reflected by increased mitochondrial
      biogenesis, but also to changes in plasma clearance and reduced TAG biosynthesis.

PMID- 29590223
TI  - Clinical Guidelines for Implant Treatment in Patients with Down Syndrome.
AB  - This study evaluated implant outcome in patients with Down syndrome (DSPs) and
      provides clinical guidelines to maximize treatment outcome. A total of 57
      implants were placed in eight DSPs. During follow-up, implant survival was
      recorded and crestal bone level was evaluated when possible. After a mean follow
      up time of 5 years, six patients with 45 implants were evaluated and an implant
      survival rate of 84.4% was recorded. A mean crestal bone loss of 1.7 mm (SD 0.9)
      was measured in three patients around 20 implants. Down syndrome is not a
      contraindication to dental implant placement, but multiple complicating factors
      yield reduced implant survival.

PMID- 29590221
TI  - Andexanet alfa effectively reverses edoxaban anticoagulation effects and
      associated bleeding in a rabbit acute hemorrhage model.
AB  - INTRODUCTION: Increasing use of factor Xa (FXa) inhibitors necessitates effective
      reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant
      human FXa, rapidly reverses the anticoagulation effects of direct and indirect
      FXa inhibitors. OBJECTIVE: To evaluate the ability of andexanet to reverse
      anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban.
      MATERIALS AND METHODS: In vitro studies characterized the interaction of
      andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa
      activity. In a rabbit model of surgically induced, acute hemorrhage, animals
      received edoxaban vehicle+andexanet vehicle (control), edoxaban (1
      mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20
      minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury. RESULTS:
      Andexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and
      dose-dependently reversed the effects of edoxaban on FXa activity and coagulation
      pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits,
      andexanet reduced anti-FXa activity by 82% (from 548+/-87 to 100+/-41 ng/ml;
      P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100+/-10 to
      21+/-6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control,
      2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the
      decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r =
      0.5951, P = 0.0035). CONCLUSION: These data demonstrate that andexanet rapidly
      reversed the anticoagulant effects of edoxaban, suggesting it could be clinically
      valuable for the management of acute and surgery-related bleeding. Correlation of
      blood loss with anti-FXa activity supports the use of anti-FXa activity as a
      biomarker for assessing anticoagulation reversal in clinical trials.

PMID- 29590224
TI  - Effect of Biologic Aging of Implants on Osseointegration in the Dog.
AB  - The objective of this preclinical study was to investigate the effect of biologic
      aging of implants on osseointegration in the canine. According to multiple
      comparisons, there was a significant difference in bone-to-implant contact (BIC)
      between control implants placed 6 months after manufacture and 2-week-old
      implants (P = .016), and between control and newly prepared implants with acid
      etching (P = .019). However, there was no significant difference in BIC between
      newly prepared implants with acid-etching and 2-week-old implants. In all groups,
      BIC at 12 weeks was significantly higher than at week 4 (P < .05). There were no
      significant differences in bone volume (BV) regardless of area and time. Biologic
      aging of implants might affect osseointegration in the bone marrow zone at 4
      weeks of healing. Although implant aging did not greatly affect BIC and BV at 12
      weeks of healing in this study, further research is required to determine an
      appropriate period of biologic aging of implants that yields significant clinical
      effects.

PMID- 29590225
TI  - Periodontal Regenerative Treatment of Intrabony Defects in the Esthetic Zone
      Using Modified Vestibular Incision Subperiosteal Tunnel Access (M-VISTA).
AB  - Periodontal regenerative treatment of intrabony defects in the esthetic zone
      often poses a significant challenge to clinicians. Various materials and
      techniques have been proposed to achieve periodontal regeneration. This article
      presents modified vestibular incision subperiosteal tunnel access (M-VISTA) for
      treatment of intrabony defects in the esthetic zone. Two cases were treated using
      the proposed approach with enamel matrix derivatives and demineralized freeze
      dried bone allograft to optimize the regenerative outcomes without affecting the
      soft tissue profile in the esthetic zone. Two different indications were
      described with addition of acellular dermal matrix and specific suturing
      techniques based on each particular clinical scenario. Clinical and radiographic
      follow-up of 18 months revealed successful outcomes of the proposed minimally
      invasive approach with no postoperative gingival recession. Patient-centered
      outcomes were highlighted as another major consideration in periodontal
      regeneration.

PMID- 29590226
TI  - Spontaneous Correction of Accentuated Retraction of Maxillary Central Incisors
      After Autogenous Graft in Midline, Mesialization, and Lingual Torque of Incisor
      Roots.
AB  - In the present clinical case, the authors report the orthodontic treatment of an
      adult patient with Class II malocclusion with periodontal disease and extensive
      bone destruction in the anterior region of the median palatine suture. Before
      orthodontic treatment, the patient presented precarious oral health. The
      treatment proposed for the case was insertion of an autogenous graft and
      subsequent orthodontic movement of the teeth to the area of the graft. The
      results obtained were correction of the malocclusion with significant improvement
      in gingival retraction and smile esthetics. With this clinical case, it could be
      concluded that well-performed orthodontic treatment can improve periodontal
      condition.

PMID- 29590228
TI  - Relationship Between Serum Uric Acid and Incident Hypertension in Patients with
      Type 2 Diabetes.
AB  - BACKGROUND: Little is known about the relationship between high baseline serum
      uric acid (SUA) and incident hypertension in patients with type 2 diabetes (T2D).
      OBJECTIVES: To evaluate the ability of baseline SUA to predict the incidence of
      hypertension in non-hypertensive patients with T2D. METHODS: The association
      between SUA and mean 20-year incidence of hypertension was examined in 1,666 non
      hypertensive patients with T2D from Isfahan Endocrine and Metabolism Research
      Center outpatient clinics, Iran. The primary outcome was incident hypertension
      defined as systolic blood pressure (BP) of 140 mmHg or higher and/or diastolic BP
      90 mmHg or higher and/or use of antihypertensive medications. The mean (standard
      error (SE)) age of participants was 49.4 years (0.25 years) with a mean (SE)
      duration of diabetes of 6.1 years (0.15 years) at initial registration. We used
      multiple logistic regression to estimate the odds ratio (OR) for the incidence of
      hypertension across quartiles of SUA, and plotted a receiver operating
      characteristic (ROC) curve to assess discrimination. RESULTS: The highest
      quartile of SUA was not associated with hypertension compared with the lowest
      quartile in multivariable adjusted models (OR: 1.22, 95% CI: 0.87, 1.73). The
      area under the ROC curve for SUA was 51.7% (95% CI: 48.9, 54.5). CONCLUSIONS:
      High initial SUA levels are not a predictor of incident hypertension in an
      Iranian T2D population.

PMID- 29590227
TI  - Polymeric Scaffolds for Pancreatic Tissue Engineering: A Review.
AB  - In recent years, there has been an alarming increase in the incidence of
      diabetes, with one in every eleven individuals worldwide suffering from this
      debilitating disease. As the available treatment options fail to reduce disease
      progression, novel avenues such as the bioartificial pancreas are being given
      serious consideration. In the past decade, the research focus has shifted towards
      the field of tissue engineering, which helps to design biological substitutes for
      repair and replacement of non-functional or damaged organs. Scaffolds constitute
      an integral part of tissue engineering; they have been shown to mimic the native
      extracellular matrix, thereby supporting cell viability and proliferation. This
      review offers a novel compilation of the recent advances in polymeric scaffolds,
      which are used for pancreatic tissue engineering. Furthermore, in this article,
      the design strategies for bioartificial pancreatic constructs and their future
      applications in cell-based therapy are discussed.

PMID- 29590229
TI  - Association of Oxytocin with Glucose Intolerance and Inflammation Biomarkers in
      Metabolic Syndrome Patients with and without Prediabetes.
AB  - OBJECTIVES: The aim of this study was to explore the differences in OXT levels in
      metabolic syndrome (MetS) subjects, newly diagnosed type 2 diabetes mellitus
      (T2D), and prediabetes subjects vs. MetS subjects without glucose intolerance
      (non-diabetic MetS). It was also intended to determine the relationship between
      plasma OXT levels and inflammatory markers in those subjects. METHODS: Along with
      45 lean and normoglycemic controls, a total of 190 MetS subjects (61 men, 129
      women) were enrolled. Colorimetric enzymatic assays of the following components
      were performed: plasma OXT, high-sensitivity C-reactive protein (hs-CRP),
      macrophage chemoattractant protein 1 (MCP-1), plasminogen activator inhibitor 1
      (PAI-1), matrix metalloproteinase 9 (MMP-9), resistin, adiponectin, leptin,
      macrophage migration inhibitory factor (MIF), tumor necrosis factor alpha (TNF
      alpha), thrompospondin 1 (TSP-1), interleukin 10 (IL-10), interleukin 6 (IL-6),
      and glucagon. RESULTS: hsCRP, PAI-1, resistin, leptin-to-adiponection-ratio
      (LAR), TNF-alpha, TSP-1, and MIF were significantly higher in both MetS groups
      (prediabetic and T2DM) than in MetS-only subjects. Leptin and MMP-9 were
      significantly higher in the MetS-T2DM group (but not in MetS-prediabetics) vs.
      MetS-only subjects. Conversely adiponectin, OXT, MCP-1, and IL-10 were
      significantly lower in both MetS groups (prediabetic and T2DM) than in MetS-only
      subjects. There was no marked discrepancy in either glucagon or IL-6 levels among
      the three MetS groups. In the entire MetS study population, OXT correlated
      substantially and proportionally with MCP-1, IL-10, and IL-6; it correlated
      negatively with HbA1c, fasting plasma glucose (FPG), PAI-1, MMP-9, TNF-alpha, TSP
      1, resistin, adiponectin, leptin, LAR, and MIF. No association could be observed
      between OXT and glucagon. CONCLUSIONS: OXT may be a substantial surrogate
      predictive/prognostic tool and putative pharmacotherapeutic target in metabolic
      anomalies and related disorders.

PMID- 29590230
TI  - Duration of Type 2 Diabetes is a Predictor of Elevated Plantar Foot Pressure.
AB  - AIMS: Elevated plantar pressure is considered a significant risk factor for
      ulceration in diabetes mellitus. The aim of this study was to determine whether
      duration of diabetes could affect plantar pressure in patients with no known
      significant comorbidity or foot pathology. METHODS: Participants with type 2
      diabetes, but without known confounding factors that could alter peak pressure,
      were matched for age, weight, and gender and categorized into 3 groups of
      diabetes duration: group 1 (1-5 yr), group 2 (6-10 yr), and group 3 (11-15 yr).
      Plantar pressures were recorded utilizing a two-step protocol at a self-selected
      speed. RESULTS: One-way analysis of variance (ANOVA) revealed significant
      differences in mean peak plantar pressures between the three groups under the 2nd
      - 4th metatarsophalangeal joint (MPJ) region of interest (ROI) (p = 0.012 and p =
      0.022, respectively) and left heel (p = 0.049). Also, a significant difference in
      mean pressure-time integral under the left 2nd - 4th MPJ ROI (p = 0.021) and
      right heel (p = 0.048) was observed. Regression analysis confirmed that mean peak
      plantar pressures in the first group (but not in the second group) were
      significantly lower than in the third group (p = 0.005). CONCLUSIONS: As the
      duration of diabetes increased, peak plantar pressure increased significantly
      under the 2nd - 4th MPJ ROIs. These findings suggest that clinicians should make
      more use of pressure mapping technology as part of their clinical management plan
      in patients with diabetes >10 yr, even if they have no complications or
      deformities, to preserve functional limbs in this high-risk population.

PMID- 29590232
TI  - The cause of abdominal mass in a child with celiac disease: Rapunzel syndrome. A
      case report.
AB  - CONTEXT: Rapunzel syndrome is a rare form of gastric trichobezoar that develops
      through outstretching of the bezoar from the stomach to the intestine. CASE
      REPORT: A 12-year-old girl who had been diagnosed with celiac disease six years
      earlier was brought to the department of pediatric gastroenterology because of
      abdominal distension. A palpable mass was detected. A trichobezoar that stretched
      to the small intestine was removed surgically. The patient was diagnosed as
      having anxiety and depressive disorder, and treatment started. Following the
      treatment, her previous trichophagia completely disappeared. CONCLUSION: Presence
      of trichobezoar should be kept in mind, especially when young girls who have
      psychiatric problems suffer from gastrointestinal symptoms.

PMID- 29590231
TI  - Association of Socio-Environmental Determinants with Diabetes Prevalence in the
      Athens Metropolitan Area, Greece: A Spatial Analysis.
AB  - OBJECTIVES: The aim of this study was to investigate the spatial variation of
      diabetes in relation to the geographical variability of socio-environmental
      characteristics in the urban districts of Athens. METHODS: A sample of 2,445
      individuals from the greater area of Athens was randomly enrolled in the ATTICA
      study between 2001 and 2002. Diabetes was defined according to American Diabetes
      Association criteria. Geographical and statistical analyses were applied to
      examine the relationship between diabetes prevalence and factors related to
      education, economic status, population density, immigrant status, and
      availability of urban green areas. Diabetes prevalence and socio-environmental
      factor mapping was based on the Geographic Information Systems (GIS) technology.
      Variograms and spatial quasi-Poisson regression analysis evaluated the
      associations of diabetes with the socio-environmental variables at the municipal
      level. RESULTS: According to the geographical analysis and mapping, the highest
      proportions of people with diabetes were found in the West sector and in one
      district of the East and South sector each. Regression analysis revealed that the
      proportion of inhabitants with higher education is negatively correlated with
      diabetes prevalence in the regional areas of Athens. CONCLUSIONS: The study
      revealed that socio-environmental status in residential areas, especially
      educational and economic levels, is correlated with diabetes prevalence at the
      aggregate level. These correlations may reflect socio-economic segregation
      patterns at the district level, and different prevalence rates of diabetes among
      individuals with higher income and educational levels.

PMID- 29590234
TI  - 30 years of the Brazilian National Health System.

PMID- 29590233
TI  - Oral squamous cell carcinoma: a clinicopathological study on 194 cases in
      northeastern Brazil. A cross-sectional retrospective study.
AB  - BACKGROUND: Only a few studies have evaluated the clinicopathological features of
      oral squamous cell carcinoma (SCC) in Brazil, and most were conducted in the most
      industrialized region of the country, i.e. the southeastern region. The aim of
      this study was to evaluate the clinicopathological features of this malignant
      neoplasm in northeastern Brazil. DESIGN AND SETTING: Retrospective study
      performed in an oral pathology laboratory in Recife, Brazil. METHODS: All cases
      of oral SCC that occurred between 2000 and 2015 were studied. Clinical data were
      recorded and histological slides were reviewed. Statistical analysis was
      performed using the chi-square test (P <= 0.05). RESULTS: A total of 194 cases
      were evaluated. The male-to-female ratio was 1.5:1. The mean age was 65.4 years,
      and only 6.6% of the cases occurred in patients younger than 41 years. Most
      tumors consisted of well-differentiated SCC (54.6%). CONCLUSIONS: The findings of
      this study highlight the higher prevalence of oral SCC among women and the
      increasing number of cases among young patients. Thus there is no specific risk
      group for oral SCC, as in the past. This fact needs to be taken into
      consideration in clinical routine care, so that apparently innocuous malignant
      lesions do not go unnoticed in these individuals.

PMID- 29590235
TI  - Effectiveness of dog collars impregnated with 4% deltamethrin in controlling
      visceral leishmaniasis in Lutzomyia longipalpis (Diptera: Psychodidade:
      Phlebotominae) populations.
AB  - BACKGROUND: There is little information on the effect of using deltamethrin
      impregnated dog collars for the control of canine visceral leishmaniasis.
      OBJECTIVES: The objective of this study was to evaluate the effectiveness of the
      use of 4% deltamethrin-impregnated collars (Scalibor(r)) in controlling visceral
      leishmaniasis in Lutzomyia longipalpis by comparing populations in intervention
      and non-intervention areas. METHODS: Phlebotomine flies were captured over 30
      months in four neighbourhoods with intense visceral leishmaniasis transmission in
      Fortaleza and Montes Claros. We calculated the rates of domicile infestation,
      relative abundance of Lu. longipalpis, and Lu. longipalpis distribution in each
      site, capture location (intra- and peridomestic locations) and area (intervention
      and non-intervention areas). FINDINGS: In the control area in Fortaleza, the
      relative abundance of Lu. longipalpis was 415 specimens at each capture site,
      whereas in the intervention area it was 159.25; in Montes Claros, the relative
      abundance was 5,660 specimens per capture site in the control area, whereas in
      the intervention area it was 2,499.4. The use of dog collars was associated with
      a reduction in captured insects of 15% (p = 0.004) and 60% (p < 0.001) in Montes
      Claros and Fortaleza, respectively. MAIN CONCLUSIONS: We observed a lower vector
      abundance in the intervention areas, suggesting an effect of the insecticide
      impregnated collars.

PMID- 29590237
TI  - Comparative study of systemic early postoperative inflammatory response among
      elderly and non-elderly patients undergoing laparoscopic cholecystectomy.
AB  - OBJECTIVE: to evaluate and compare the early postoperative period systemic
      inflammatory response between elderly and non-elderly patients submitted to
      laparoscopic cholecystectomy, mainly performing a quantitative analysis of
      interleukin-6 (IL-6), a marker of inflammatory activity systemic. METHODS: we
      compared a series of cases over a period of six months at the Gaffree and Guinle
      University Hospital of the Federal University of the State of Rio de Janeiro,
      involving 60 patients submitted to elective laparoscopic cholecystectomy. We used
      non-probabilistic sampling for convenience, selecting, from the inclusion
      criteria, the first 30 patients aged 18-60 years, who comprised group I, and 30
      patients with age equal to or greater than 60 years, who formed group II.
      RESULTS: the 60 patients involved were followed for at least 30 days after
      surgery and there were no complications. There was no conversion to open surgery.
      The values of the medians found in the IL-6 dosages for the preoperative period,
      three hours after the procedure and 24 hours after surgery were, respectively,
      3.1 vs. 4.7 pg/ml, 7.3 vs. 14.1 pg/ml and 4.4 vs 13.3 pg/ml. CONCLUSION: Elderly
      patients were more responsive to surgical trauma and had elevated IL-6 levels for
      a longer period than the non-elderly group.

PMID- 29590236
TI  - Evaluation of the recombinant antigens Wb14 and WbT for the capture antibody
      diagnosis of lymphatic filariasis.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease caused mainly by the
      Wuchereria bancrofti worm and that affects up to 120 million people worldwide. LF
      is the second cause of chronic global deformity, responsible for 15 million
      people with lymphedema (elephantiasis) and 25 million men with scrotal hydrocele.
      Its diagnosis is still associated with numerous difficulties, such as the sample
      collection periods (microfilaria nocturnal periodicity) and limited diagnostic
      kits. OBJECTIVES: The aim of this work was to evaluate two recombinant antigens
      (Wb14 and WbT) as part of an enzyme-linked immunosorbent assay (ELISA) based
      antibody capture tests for LF. METHODS: The recombinant antigens rWb14 and rWbT
      were expressed in Escherichia coli BL21 and an antibody capture ELISA was
      performed. For this, sera were used from microfilaremic individuals with W.
      bancrofti (MF), chronic pathology (CP), individuals infected with Strongyloides
      (SP) and healthy controls from endemic (EN) and non-endemic (NE) areas. FINDINGS:
      Both tests showed similar results, with 90% sensitivity and 96.6% specificity. In
      comparison with the BM14 ELISA commercial test, the Wb14 and WbT antigens
      performed with identical sensitivity but greater specificity. Reduced positivity
      with the CP suggested a potential to monitor cure. This was not confirmed,
      however, when sera from individuals up to seven years after treatment were
      assayed. MAIN CONCLUSIONS: The Wb14 and WbT ELISAs were considered efficient and
      promising diagnostic tests. Due to the importance of antibody capture analysis to
      evaluate the Global Program to Eliminate Lymphatic Filariasis (GPELF), the tests
      proposed here appear as great alternatives to the available commercial system.

PMID- 29590238
TI  - Resuscitative endovascular balloon occlusion of the aorta (REBOA): an updated
      review.
AB  - In a current scenario where trauma injury and its consequences account for 9% of
      the worlds causes of death, the management of non-compressible torso hemorrhage
      can be problematic. With the improvement of medicine, the approach of these
      patients must be accurate and immediate so that the consequences may be minimal.
      Therefore, aiming the ideal method, studies have led to the development of
      Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This procedure
      has been used at select trauma centers as a resuscitative adjunct for trauma
      patients with non-compressible torso hemorrhage. Although the use of this
      technique is increasing, its effectiveness is still not clear. This article aims,
      through a detailed review, to inform an updated view about this procedure, its
      technique, variations, benefits, limitations and future.

PMID- 29590239
TI  - Instructional design in the development of an online course on Basic Life
      Support.
AB  - OBJECTIVE: To develop and evaluate an online course on Basic Life Support.
      METHOD: Technological production research of online course guided by the ADDIE
      (Analysis, Design, Development, Implementation, Evaluation) instructional design
      model based on Andragogy and the Meaningful Learning Theory. The online course
      was constructed in the platform Moodle, previously assessed by a group of
      experts, and then presented to the students of the Nursing School of the
      University of Sao Paulo, who assessed it at the end of the course. RESULTS: The
      course was evaluated by the experts and obtained a mean score of 0.92 (SD 0.15),
      considered as good quality (between 0.90-0.94), and by the students, with a mean
      score of 0.95 (SD 0.03), considered as high quality (0.95-1.00). CONCLUSION: The
      instructional design used was found to be appropriate to the development of the
      online course. As an active educational strategy, it contributed to the learning
      on Basic Life Support during cardiac arrest-related procedures in adults. In view
      of the need for technological innovations in education and systematization of
      care in cardiopulmonary resuscitation, the online course allows the establishment
      of continuous improvement processes in the quality of resuscitation in the care
      provided by students and professionals.

PMID- 29590240
TI  - Erratum: The practice of reporting adverse events in a teaching hospital.
AB  - [This corrects the article doi: 10.1590/S1980-220X2016045503243].

PMID- 29590241
TI  - "We only have access as a favor, don't we?" The perception of homeless population
      on the human rights to water and sanitation.
AB  - The human rights to water and sanitation (HRWS) state that all human beings have
      the right to safe access to water and sanitation in a non-discriminatory manner.
      However, vulnerable populations frequently have these rights violated, which
      impacts their health and quality of life, exacerbating social exclusion as in the
      case of homeless people. In Belo Horizonte, Minas Gerais State, Brazil, 1,827
      people were living on the streets in 2013. This study presents the evaluation of
      the conditions and perceptions of this population on their rights to water and
      sanitation access. It has been observed that access to both water and sanitation
      is precarious and that the normative content, as well as the human rights
      principles, are highly violated. In conclusion, we observed that this group
      suffers violations of HRWS and that these are associated with the violation of
      other rights such as the right to the city, dwelling and health. Such violations
      have negative impacts on the economic and social life of this group, increasing
      discrimination and exclusion. This study draws attention to the importance of
      encouraging the social participation of this group in the decision-making
      processes of water and sanitation management within the framework of HRWS, in its
      capacity to be a tool for social transformation, generating empowerment,
      promoting health, dignity and citizenship.

PMID- 29590242
TI  - [Sources of medicines for chronic patients using the Brazilian Unified National
      Health System].
AB  - The article aimed to identify the sources of medicines for users of the Brazilian
      Unified National Health System (SUS) that reported chronic non-communicable
      diseases, characterizing the group according to demographic, socioeconomic, and
      health variables in the different regions of Brazil. Data were analyzed from the
      National Survey on Access, Use, and Promotion of Rational Use of Medicines in
      Brazil (PNAUM), a cross-sectional population-based study. The dependent variable
      was "source of medicines", and the associations were analyzed with demographic,
      socioeconomic, and health status variables. Users that obtained care and
      medicines solely in the SUS were designated here as SUS-exclusive. Some 39% of
      persons obtained their medicines from SUS pharmacies and 28.5% from other
      sources. The study found 42.9%, 41.8%, 40.2%, and 31% of exclusive SUS users in
      the Southeast, South, North, and Northeast regions of Brazil, respectively. SUS
      users have the SUS as their primary source of medicines, but there is also a
      relevant share from other sources, suggesting problems with access in the SUS. In
      the South and Southeast regions, the population relies less on private pharmacies
      than in the Northeast and North.

PMID- 29590243
TI  - [The concept of vulnerability and its meanings for public policies in health and
      social welfare].
AB  - Are concepts of vulnerability capable of influencing social practices and
      citizenship in the fields of health and social welfare? The article critically
      assesses this question through a comprehensive-interpretative approach to
      hermeneutics-dialectics and a review of the literature produced on the theme in
      the last two decades. There is no vast theoretical output on the theme. However,
      although conceptually imprecise, the term "vulnerability" expands the
      understanding of the multiple factors that weaken subjects in the exercise of
      their citizenship. Professional action in the sphere of health and social welfare
      policies and the social imaginary are forged by the incorporation of concepts
      that can either reduce or reinforce vulnerabilities.

PMID- 29590244
TI  - [A nonlinear model for localization of hospital services as an indicator of
      accessibility].
AB  - The study proposes a differentiated approach to the localization of public
      services (unlike methods focusing solely on locational efficiency in the
      distribution of such services), with a nonlinear model that incorporates an
      accessibility indicator and allows rejecting solutions in which accessibility
      fails to comply with acceptably established minimum parameters. The method aims
      to minimize the total time spent by a region's population to reach a public
      services network, while controlling the range between the highest and lowest
      accessibility to the services. The resulting solution is not as efficient as
      other models (e.g., p-median) in relation to total cost for the population as a
      whole to access the system, but it seeks to prevent the most distant areas from
      experiencing greater difficulty due to their disproportional traveling time. The
      model was tested in a region in the hospital network of the State of Santa
      Catarina, Brazil, and the results show that incorporation of the indicator
      suggests improvement when compared to the current distribution of hospitals in
      that area. The proposed methodology can be a useful tool for planning balanced
      resource allocation during installation of health services for the population.

PMID- 29590245
TI  - Keeping a watchful eye on the food giants and cleansing the temple of nutritional
      medicine and epidemiology.

PMID- 29590246
TI  - Carotid intima-media thickness in the Brazilian Longitudinal Study of Adult
      Health (ELSA-Brasil): a narrative review.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT), as measured by ultrasound, has
      been used in large studies as a non-invasive marker for subclinical
      atherosclerosis. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
      is a cohort of 15,105 civil servants in six Brazilian cities that included CIMT
      evaluation in its baseline assessment. The aim of the present narrative review
      was to provide an overview of ELSA-Brasil CIMT articles published up to July 31,
      2017. DESIGN AND SETTING: Narrative review of ELSA-Brasil CIMT studies using
      baseline assessment data. METHODS: We searched PubMed for the terms "ELSA-Brasil"
      and "intima-media". This search yielded 21 published articles using CIMT data
      from the ELSA-Brasil baseline assessment, which were included in this review. We
      also present information about intima-media thickness assessment from ongoing
      onsite reevaluations of the study participants. RESULTS: Most published studies
      focused on the association with traditional and novel cardiovascular risk
      factors. Studies also presented information about the ELSA-Brasil CIMT protocol
      at baseline and CIMT value distribution in this large sample. CONCLUSIONS:
      Analyses on the ELSA-Brasil data led to important insights on CIMT interpretation
      and physiology. Besides the highlighted contributions which have already been
      made in this field, new data gathered during the ongoing third onsite assessment
      will enable investigation of substantially new research questions.

PMID- 29590248
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.1590/1516-3180.2017.0277100917].

PMID- 29590247
TI  - What do Cochrane systematic reviews say about non-surgical interventions for
      urinary incontinence in women?
AB  - BACKGROUND: Urinary incontinence is a highly prevalent condition that impacts
      self-esteem and overall quality of life. Many non-surgical treatment options are
      available, ranging from pharmacological approaches to pelvic exercises. We aimed
      to summarize the available evidence regarding these non-surgical interventions.
      DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of
      Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de Sao
      Paulo (EPM-UNIFESP). METHODS: A sensitive search was conducted to identify all
      Cochrane systematic reviews that fulfilled the inclusion criteria. Titles and
      abstracts were screened by two authors. RESULTS: We included 20 Cochrane
      systematic reviews: 4 assessing methods of vesical training, 3 evaluating
      pharmacological interventions, 4 studying pelvic floor muscle training approaches
      and 9 aimed at other alternatives (such as urethral injections, weighted vaginal
      cone use, acupuncture, biostimulation and radiofrequency therapy). The reviews
      found that the evidence regarding the benefits of these diverse interventions
      ranged in quality from low to high. CONCLUSIONS: This review included 20 Cochrane
      systematic reviews that provided evidence (of diverse quality) for non
      pharmacological interventions for patients with urinary incontinence. Moderate to
      high quality of evidence was found favoring the use of pelvic floor muscle
      training among women with urinary incontinence. To establish solid conclusions
      for all the other comparisons, further studies of good methodological quality are
      needed.

PMID- 29590249
TI  - Quantitative and qualitative variables of semen from surubim do Iguacu,
      Steindachneridion melanodermatum Garavello, 2005 (Siluriformes: Pimelodidae).
AB  - The objective of the present work was to assess the qualitative and quantitative
      characteristics of semen from the surubim do Iguacu (Steindachneridion
      melanodermatum). Induced spermiation was achieved in eleven males with mean
      weight of 1.76 +/- 0.48 kg and average age of two years and semen was collected
      by stripping. The average volume was 1.34 +/- 0.73 mL. The duration of sperm
      motility was 154.4 +/- 72.6 and 149.0 +/- 77.5 seconds after activation with
      hatchery water and distilled water, respectively. The sperm concentration
      estimated by hemocytometer was 5.423 +/- 2.155 x 1010 spermatozoa/mL. The results
      indicate that S. melanodermatum semen is easily obtained during the spawning
      season and the seminal characteristics are adequate insemination and subsequent
      in vitro fertilization.

PMID- 29590250
TI  - Thrips species (Insecta: Thysanoptera) associated with flowers in a restinga
      fragment in northeastern Brazil.
AB  - With the growing volume of research involving Thysanoptera in Brazil, studies
      were carried out to improve our understanding of the diversity of thrips in areas
      where the fauna has historically been neglected. Accordingly, we recorded the
      diversity of thrips (Insecta: Thysanoptera) associated with a restinga fragment
      located on the campus of the State University of Ceara (UECE), Fortaleza, Ceara
      state, and computed the estimated richness and diversity indices. Samples were
      collected from 2011 through 2013 from flowers of 86 plant species. The material
      was taken to the Laboratory of Insect-Plant Interaction, where thrips were
      screened under stereomicroscope. We collected 456 adults and 58 immatures,
      representing 14 species, in addition to one unidentified species of Treherniella.
      Microcephalothrips abdominalis was found on a large number of host plants, and
      Frankliniella insularis was the most common species. About two-thirds of the
      total richness of thrips species was associated with three plant families
      (Amaranthaceae, Caesalpiniaceae and Poaceae); six thrips species were each
      associated with only one plant species. The richness of the species collected was
      close to that estimated by Bootstrap and Jackknife 1 analysis. The Shannon-Wiener
      (H') and Simpson (D) diversity indexes were 1,7607 and 0.7769, respectively.
      Although the species are common, 46 new associations between plant species and
      thrips were established, 13 of which are true host associations, which
      demonstrates the importance of coastal vegetation in maintaining populations of
      thrips.

PMID- 29590251
TI  - Responses of antioxidant enzymes, photosynthetic pigments and carbohydrates in
      micropropagated Pitcairnia encholirioides L.B. Sm. (Bromeliaceae) under ex vitro
      water deficit and after rehydration.
AB  - In this study, the activities of antioxidant enzymes, photosynthetic pigments,
      proline and carbohydrate contents in Pitcairnia encholirioides under ex vitro
      conditions of water deficit were evaluated. Results show that plants under
      progressive water stress, previously in vitro cultured in media supplemented with
      30 g L-1 sucrose and GA3, accumulated more proline and increased peroxidase (POD)
      activity and the contents of photosynthetic pigments and carbohydrates. For
      plants previously in vitro cultured with 15 g L-1 sucrose and NAA, no differences
      were found for proline content and there were reductions in activities of
      peroxidase (POD), catalase (CAT) and poliphenoloxidase (PPO), and in contents of
      carbohydrates, with progress of ex vitro water deficit. After rehydration, plants
      showed physiological recovery, with enzymatic activities and contents of
      metabolites similar to those found in the controls not submitted to dehydration,
      regardless of the previous in vitro culture conditions. These results show that
      micropropagated P. encholirioides has high tolerance to dehydration once in ex
      vitro conditions, which can ensure the survival of plants from tissue culture
      when transferred to its natural environment, emphasizing the importance of such
      biotechnology for the propagation of endangered species.

PMID- 29590252
TI  - Morphology of the spermatheca of Triatoma lecticularia (Hemiptera: Reduviidae)
      (Stal, 1859).
AB  - Triatoma lecticularia (Hemiptera: Reduviidae) (Stal, 1859) is a potential vector
      of Chagas's disease and the comprehension of its reproductive biology is an
      important tool to control this insect. In the reproductive tract of female
      insects, the spermatheca plays a crucial role storing male spermatozoa after
      mating. Whithin insects the spermatheca shows a wide morphological diversity and
      the analysis of this characteristic can contribute to understand the reproductive
      biology of the species. This study describes the histology and histochemistry of
      the spermatheca of T. lecticularia. Females have a pair of elongated spermathecal
      reservoirs without associated accessory gland. The reservoir opens into the
      common oviduct via a narrow muscular duct. The reservoir epithelium has single
      layer of columnar secretory cells. The control of the release of spermatozoa from
      the spermatheca occurs via the muscular duct. The anatomical features of the
      spermatheca of T. lecticularia resemble those described of other Reduviidae.
      However, the histological and histochemical features of spermatheca observed in
      T. lecticularia were important to explain the maintenance of the viability of the
      spermatozoa stored.

PMID- 29590253
TI  - Electrocuted! Amphibian deaths caused by electric discharge.

PMID- 29590254
TI  - Xanthine oxidase activity in patients with age-related cataract associated with
      hypertension.
AB  - Reactive oxygen species and lipid peroxidation are important factors that
      contribute to the development of age-related cataract. The study included 130
      patients with age-related cataract, 69 of whom were diagnosed with hypertension
      (HT), 20 with hypertension and type 2 diabetes mellitus (DM), and 41 had no
      accompanying condition. The following parameters were measured in the serum of
      the examinees: products of lipid peroxidation malondialdehyde (MDA) and
      lipofuscin-like fluorophores (LLF), activity of prooxidative enzymes xanthine
      oxidase (XO) and myeloperoxidase (MPO), antioxidant enzymes superoxide dismutase
      (SOD) and glutathione peroxidase (GPx), the concentration of thiol groups, and
      the ferric reducing activity of plasma. The activity of prooxidative enzymes XO
      and MPO was higher in the plasma of patients with HT (XO=9.0+/-1.2 U/L;
      MPO=77.3+/-8.4 U/L) and with HT and DM (XO=11.9+/-0.9 U/L; MPO=89.5+/-5.0 U/L)
      compared to patients with age-related cataract (XO=6.2+/-0.9 U/L; MPO=52.4+/-6.3
      U/L; P<0.01). Our research has shown that patients with age-related cataract and
      hypertension were exposed to increased oxidative damage of biomolecules, based on
      the increased plasma LLF and MDA content and decreased levels of thiol groups.
      Oxidative changes of biomolecules in these patients were associated with
      increased activity of the XO, MPO, and GPx enzymes and a lower extracellular SOD
      activity and total ferric reductive ability of plasma.

PMID- 29590255
TI  - Use of cardiopulmonary exercise testing to assess early ventilatory changes
      related to occupational particulate matter.
AB  - Spirometry has been used as the main strategy for assessing ventilatory changes
      related to occupational exposure to particulate matter (OEPM). However, in some
      cases, as one of its limitations, it may not be sensitive enough to show
      abnormalities before extensive damage, as seen in restrictive lung diseases.
      Therefore, we hypothesized that cardiopulmonary exercise testing (CPET) may be
      better than spirometry to detect early ventilatory impairment caused by OEPM. We
      selected 135 male workers with at least one year of exposure. After collection of
      self-reported socioeconomic status, educational level, and cardiovascular risk
      data, participants underwent spirometry, CPET, body composition assessment
      (bioelectrical impedance), and triaxial accelerometry (for level of physical
      activity in daily life). CPET was performed using a ramp protocol on a treadmill.
      Metabolic, cardiovascular, ventilatory, and submaximal relationships were
      measured. We compared 52 exposed to 83 non-exposed workers. Multiple linear
      regressions were developed using spirometry and CPET variables as outcomes and
      OEPM as the main predictor, and adjusted by the main covariates. Our results
      showed that OEPM was associated with significant reductions in peak minute
      ventilation, peak tidal volume, and breathing reserve index. Exposed participants
      presented shallower slope of DeltaVT/DeltalnVE (breathing pattern), i.e.,
      increased tachypneic breathing pattern. The OEPM explained 7.4% of the
      DeltaVT/DeltalnVE variability. We found no significant influence of spirometric
      indices after multiple linear regressions. We conclude that CPET might be a more
      sensitive feature of assessing early pulmonary impairment related to OEPM. Our
      cross-sectional results suggested that CPET is a promising tool for the screening
      of asymptomatic male workers.

PMID- 29590256
TI  - Unsteady walking as a symptom in type 2 diabetes mellitus: independent
      association with depression and sedentary lifestyle and no association with
      diabetic neuropathy.
AB  - The purpose of this study was to look at the determinants of the unsteady walking
      (UW) symptom in patients with type 2 diabetes mellitus (T2DM) by defining if UW
      and/or the Diabetic Neuropathy Symptoms Score (DNSS) are associated with positive
      scores in Beck's Depression Inventory (BDI) and with a positive Michigan
      Neuropathy Screening Instrument score (MNSI). We evaluated 203 T2DM patients
      without visible gait disturbances. They were divided into UW (+) and UW (-) or
      DNSS (+) and DNSS (-) according to symptoms. We found a prevalence of 48.3% for
      UW (+) and of 63% for DNSS (+) in our sample. In univariate analysis, the
      presence of UW was significantly associated with waist circumference (P=0.024),
      number of comorbidities (P=0.012), not practicing physical exercise (P=0.011),
      positive BDI score (P=0.003), presence of neuropathic symptoms by the MNSI
      questionnaire (P<0.001), and positive diabetic neuropathy screening by MNSI
      (P=0.021). In multivariate analysis, UW (used as a dependent variable) was
      independently associated with a positive BDI score (P<0.001; 95%CI=1.01-1.03),
      T2DM duration (P=0.023; 95%CI=1.00-1.03), number of co-morbidities (P=0.032;
      95%CI=1.01-1.37), and a sedentary lifestyle (P=0.025; 95%CI=1.06-2.5). The UW
      symptom and a positive DNSS are more closely related to a positive score for
      depression than to presence of neuropathy in T2DM.

PMID- 29590257
TI  - Renovascular hypertension increases serum TNF and CX3CL1 in experimental
      Trypanosoma cruzi infection.
AB  - Trypanosoma cruzi triggers a progressive inflammatory response affecting
      cardiovascular functions in humans and experimental models. Angiotensin II, a key
      effector of the renin-angiotensin system, plays roles in mediating hypertension,
      heart failure, and inflammatory responses. T. cruzi and AngII can induce
      inflammatory responses by releasing inflammatory mediators. The aim of this study
      was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators
      in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats
      infected with T. cruzi. Our data showed an increase in serum AngII in uninfected
      and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham)
      animals. The baseline systolic blood pressure was higher in both uninfected and
      infected 2K1C rats. Despite no difference in circulating parasites in the acute
      phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post
      infection in 2K1C rats in association with higher cardiac inflammatory
      infiltration. In summary, AngII-induced hypertension associated with T. cruzi
      infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat
      model, thereby intensifying cardiac inflammatory infiltration and worsening the
      underlying inflammation triggered by this protozoan.

PMID- 29590258
TI  - Human dental pulp stem cell adhesion and detachment in polycaprolactone
      electrospun scaffolds under direct perfusion.
AB  - Cell adhesion in three-dimensional scaffolds plays a key role in tissue
      development. However, stem cell behavior in electrospun scaffolds under perfusion
      is not fully understood. Thus, an investigation was made on the effect of flow
      rate and shear stress, adhesion time, and seeding density under direct perfusion
      in polycaprolactone electrospun scaffolds on human dental pulp stem cell
      detachment. Polycaprolactone scaffolds were electrospun using a solvent mixture
      of chloroform and methanol. The viable cell number was determined at each tested
      condition. Cell morphology was analyzed by confocal microscopy after various
      incubation times for static cell adhesion with a high seeding density. Scanning
      electron microscopy images were obtained before and after perfusion for the
      highest flow rate tested. The wall pore shear stress was calculated for all
      tested flow rates (0.005-3 mL/min). An inversely proportional relationship
      between adhesion time with cell detachment under perfusion was observed. Lower
      flow rates and lower seeding densities reduced the drag of cells by shear stress.
      However, there was an operational limit for the lowest flow rate that can be used
      without compromising cell viability, indicating that a flow rate of 0.05 mL/min
      might be more suitable for the tested cell culture in electrospun scaffolds under
      direct perfusion.

PMID- 29590259
TI  - Individual variation is the key to the development of a vaccine against
      Staphylococcus aureus: a comparative study between mice lineages.
AB  - Bacterial infections occur worldwide and are a major public health problem. Among
      pathogens, Staphylococcus aureus is the main causative agent of bacterial
      diseases in the world. This study aimed to evaluate which components of the
      immune system could act protectively against a S. aureus infection in
      intradermally immunized mice. C57BL/6 and A/j mice were immunized intradermally
      with S. aureus inactivated by heat and then challenged with viable strains in an
      air pouch model. At 6, 12, and 24 h after the challenge, euthanasia was
      performed, and the cellular profile of the inflammatory infiltrate, cytokines,
      and the bacterial load were evaluated in the air pouch lavages. Immunized mice
      demonstrated that the intradermal immunization with S. aureus promoted protection
      in C57BL/6 mice by reducing the bacterial, which was correlated with increased
      serum concentration of IgG antibodies (IgG1 and IgG2a) against S. aureus. The
      increase in IgG2a antibody levels was correlated with a decrease of bacterial
      load in intradermally immunized C57BL/6 mice, along with production of IL-17A at
      the inflammation site, as well as IgG1consumption. Similar results were not found
      in the A/j lineage. In conclusion, a vaccine against S. aureus should focus more
      on the individual characteristics of the host because it is a determinant factor
      for the success of the immunization.

PMID- 29590260
TI  - Effect of pre-exercise carbohydrate availability on fat oxidation and energy
      expenditure after a high-intensity exercise.
AB  - The aim of this study was to test the hypothesis that reduced pre-exercise
      carbohydrate (CHO) availability potentiates fat oxidation after an exhaustive
      high-intensity exercise bout. Eight physically active men underwent a high
      intensity exercise (~95% VO2max) until exhaustion under low or high pre-exercise
      CHO availability. The protocol to manipulate pre-exercise CHO availability
      consisted of a 90-min cycling bout at ~70% VO2max + 6 * 1-min at 125% VO2max with
      1-min rest, followed by 48 h under a low- (10% CHO, low-CHO availability) or high
      CHO diet (80% CHO, high-CHO availability). Time to exhaustion was shorter and
      energy expenditure (EE) lower during the high-intensity exercise in low- compared
      to high-CHO availability (8.6+/-0.8 and 11.4+/-1.6 min, and 499+/-209 and 677+/
      343 kJ, respectively, P<0.05). Post-exercise EE was similar between low- and high
      CHO availability (425+/-147 and 348+/-54 kJ, respectively, P>0.05), but post
      exercise fat oxidation was significantly higher (P<0.05) in low- (7,830+/-1,864
      mg) than in high-CHO availability (6,264+/-1,763 mg). The total EE (i.e.,
      exercise EE plus post-exercise EE) was similar between low- and high-CHO
      availability (924+/-264 and 1,026+/-340 kJ, respectively, P>0.05). These results
      suggest that a single bout of high-intensity exercise performed under low-CHO
      availability increased post-exercise fat oxidation, and even with shorter
      exercise duration, both post-exercise EE and total EE were not impaired.

PMID- 29590261
TI  - Performance during a strenuous swimming session is associated with high blood
      lactate: pyruvate ratio and hypoglycemia in fasted rats.
AB  - The aim of this study was to investigate the effect of lactatemia elevation and
      glycemia reduction on strenuous swimming performance in fasted rats. Three rats
      were placed in a swimming tank at the same time. The first rat was removed
      immediately (control group) and the remaining ones were submitted to a strenuous
      swimming session. After the second rat was exhausted (Exh group), the third one
      was immediately removed from the water (Exe group). According to the period of
      time required for exhaustion, the rats were divided into four groups: low
      performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary
      performance (13-17 min), and high performance (18-22 min). All rats were removed
      from the swimming tanks and immediately killed by decapitation for blood
      collection or anesthetized for liver perfusion experiments. Blood glucose,
      lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver
      lactate uptake and its conversion to glucose were evaluated. Exhaustion in low
      and low-intermediary performance were better associated with higher
      lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and
      high performance was better associated with hypoglycemia. Lactate uptake and
      glucose production from lactate in livers from the Exe and Exh groups were
      maintained. We concluded that there is a time sequence in the participation of
      lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous
      swimming section in fasted rats. The liver had an important participation in
      preventing hyperlactatemia and hypoglycemia during swimming through lactate
      uptake and its conversion to glucose.

PMID- 29590263
TI  - Cognitive-behavioral group therapy for intermittent explosive disorder:
      description and preliminary analysis.
AB  - OBJECTIVES: To evaluate the efficacy of a group therapy based on cognitive
      behavioral techniques customized for intermittent explosive disorder (IED). The
      current report presents the preliminary results of a clinical trial comparing pre
      and post-intervention scores in different anger dimensions. METHODS: The studied
      sample consisted of 84 treatment-seeking subjects. The mean (standard deviation)
      age was 43.0 (11.9) years, and 78% were male. The therapeutic group program
      consisted of 15 weekly sessions plus three maintenance sessions. The sessions
      lasted approximately 90 minutes each. RESULTS: No differences were found in
      demographic profile and pre-treatment status between subjects who completed
      treatment (n=59) and dropouts (n=25). Comparison of State-Trait Anger Expression
      Scale (STAXI) scores pre- and post-treatment showed statistically significant
      changes in all anger scales and subscales of the questionnaire. CONCLUSION: This
      preliminary report is a significant addition to currently scarce clinical data.
      Our findings provide further evidence that structured cognitive-behavioral group
      therapy, with a focus on anger management and cognitive coping, may be a
      promising approach to the treatment of IED.

PMID- 29590262
TI  - PCR-RFLP assay as an option for primary HPV test.
AB  - Persistent human papillomavirus (HPV) infection is an essential factor of
      cervical cancer. This study evaluated the analytical performance of restriction
      fragment length polymorphism polymerase chain reaction (PCR-RFLP) assay compared
      to PapilloCheck(r) microarray to identify human papilloma virus (HPV) in cervical
      cells. Three hundred and twenty-five women were analyzed. One sample was used for
      conventional cytology and another sample was collected using BD SurePathTM kit
      for HPV tests. Eighty samples (24.6%) were positive for HPV gene by PCR-Multiplex
      and were then submitted to PCR-RFLP and PapilloCheck(r) microarray. There was a
      genotyping agreement in 71.25% (57/80) on at least one HPV type between PCR-RFLP
      and PapilloCheck(r) microarray. In 22 samples (27.5%), the results were
      discordant and those samples were additionally analyzed by DNA sequencing. HPV 16
      was the most prevalent HPV type found in both methods, followed by HPVs 53, 68,
      18, 39, and 66 using PCR-RFLP analysis, and HPVs 39, 53, 68, 56, 31, and 66 using
      PapilloCheck(r) microarray. In the present study, a perfect agreement using
      Cohen's kappa (kappa) was found in HPV 33 and 58 (kappa=1), very good for HPV 51,
      and good for types 16, 18, 53, 59, 66, 68, 70, and 73. PCR-RFLP analysis
      identified only 25% (20/80) HPV coinfection, and PapilloCheck(r) microarray found
      62.5% (50/80). Our Cohen's kappa results indicate that our in-house HPV
      genotyping testing (PCR-RFLP analysis) could be applied as a primary HPV test
      screening, especially in low income countries. If multiple HPV types are found in
      this primary test, a more descriptive test, such as PapilloCheck(r) microarray,
      could be performed.

PMID- 29590264
TI  - Psychometric properties of the EUROHIS-QOL 8-item index (WHOQOL-8) in a Brazilian
      sample.
AB  - OBJECTIVE: To test the psychometric properties of the EUROHIS-QOL 8-item index in
      a Brazilian sample. METHODS: The sample consisted of 151 patients and 174 healthy
      controls (n=325). Several psychometric properties were tested. RESULTS:
      Reliability showed good internal consistency (Cronbach's alpha = 0.81). The
      measure showed good discriminant validity between patients and healthy controls
      (mean1 = 3.32, SD1 = 0.70; mean2 = 3.77, SD2 = 0.63, t = 6.12, p < 0.001).
      Convergent validity showed significant correlations (p < 0.001) between the
      EUROHIS-QOL 8-item index and all domains of the WHOQOL-Bref (overall r = 0.47;
      general health r = 0.54; physical r = 0.69; psychological r = 0.62; social
      relationship r = 0.55; environment r = 0.55) and between the EUROHIS-QOL 8-item
      index and the domains of the SF-36, except for the social domain (p = 0.38). On
      Rasch analysis of unidimensionality, general fit measures showed adequate
      performance. The EUROHIS-QOL 8-item index also showed good fit on confirmatory
      factor analysis (CFA) (chi-square = 18.46, degrees of freedom [df] = 15;
      comparative fit index [CFI] = 0.99; root mean square error of approximation
      [RMSEA] = 0.03; goodness of fit index [gfi] = 0.99; root mean square residual
      [RMR] = 0.03; p = 24). CONCLUSION: The EUROHIS-QOL 8-item index showed good
      psychometric properties. It is a reliable quality of life measure that can be
      used in Brazilian populations.

PMID- 29590265
TI  - The association between social skills deficits and family history of mood
      disorder in bipolar I disorder.
AB  - OBJECTIVE: To compare social skills and related executive functions among bipolar
      disorder (BD) patients with a family history of mood disorders (FHMD), BD
      patients with no FHMD and healthy control (HCs). METHODS: We evaluated 20
      euthymic patients with FHMD, 17 euthymic patients without FHMD, and 31 HCs using
      the Social Skills Inventory (SSI) and a neuropsychological battery evaluating
      executive function, inhibitory control, verbal fluency and estimated
      intelligence. RESULTS: Both BD groups had lower SSI scores than controls. Scores
      for one subfactor of the social skills questionnaire, conversational skills and
      social performance, were significantly lower among patients with FHMD than among
      patients without FHMD (p = 0.019). Both groups of BD patients exhibited
      significant deficits in initiation/inhibition, but only BD patients with FHMD had
      deficits in verbal fluency, both compared to HC. There were no associations
      between social skills questionnaire scores and measures of cognitive function.
      CONCLUSION: Euthymic BD patients have lower social skills and executive function
      performance than HC. The presence of FHMD among BD patients is specifically
      associated with deficits in conversational and social performance skills, in
      addition to deficits in verbal fluency. Both characteristics might be associated
      with a common genetically determined pathophysiological substrate.

PMID- 29590266
TI  - Maintenance use of ketamine for treatment-resistant depression: an open-label
      pilot study.

PMID- 29590267
TI  - Skin picking disorder comorbid with ADHD successfully treated with
      methylphenidate.

PMID- 29590268
TI  - Is the regulation of Z-drugs in Brazil in line with scientific research and
      international standards?

PMID- 29590269
TI  - Zika virus infection and psychosis.

PMID- 29590270
TI  - Dietary Protein and Preservation of Physical Functioning Among Middle-Aged and
      Older Adults in the Framingham Offspring Study.
AB  - Dietary protein may help prevent age-related declines in strength and functional
      capacity. This study examines the independent relationship between dietary
      protein and longitudinal changes in physical functioning among adults
      participating in the Framingham Offspring Study from examination 5 (1991-1995) to
      examination 8 (2005-2008). Protein intakes were derived from 3-day diet records
      during examinations 3 and 5; functional status was determined over 12 years using
      7 items selected from standardized questionnaires. Multivariable models adjusted
      for age, sex, education, physical activity, smoking, height, and energy intake.
      Functional tasks that benefitted most from a higher-protein diet (>=1.2 g/kg/day
      vs. <0.8 g/kg/day) were doing heavy work at home, walking 1/2 mile (0.8 km),
      going up and down stairs, stooping/kneeling/crouching, and lifting heavy items.
      Those with higher protein intakes were 41% less likely (95% CI: 0.43, 0.82) to
      become dependent in 1 or more of the functional tasks over follow-up. Higher
      physical activity and lower body mass index were both independently associated
      with less functional decline. The greatest risk reductions were found among those
      with higher protein intakes combined with either higher physical activity, more
      skeletal muscle mass, or lower body mass index. This study demonstrates that
      dietary protein intakes above the current US Recommended Daily Allowance may slow
      functional decline in older adults.

PMID- 29590274
TI  - A Promising Future Role for Neuroimaging in Tracking and Predicting Relapse in
      Major Depressive Disorder.

PMID- 29590275
TI  - Hair Loss Associated With Cucurbit Poisoning.

PMID- 29590276
TI  - Evaluation and Management of Self-injury in a Child With a Rare Genomic Variant.

PMID- 29590277
TI  - Late Stroke After Coronary Artery Bypass Grafting.

PMID- 29590278
TI  - Rechallenge With Nivolumab After Vemurafenib Treatment of Initially Nivolumab
      Resistant Advanced Melanoma.

PMID- 29590279
TI  - Comparison of Drug Discontinuation, Effectiveness, and Safety Between Clinical
      Trial Eligible and Ineligible Patients in BADBIR.
AB  - Importance: Patients with psoriasis enrolled in clinical trials of biologics may
      not be representative of the real-world population. There is evidence that
      patients ineligible for such trials have a greater risk of serious adverse events
      (SAEs), but the effect on drug discontinuation and effectiveness are unknown.
      Objective: To determine whether (1) drug discontinuation, (2) effectiveness, and
      (3) rates of SAEs differ in patients with psoriasis categorized as eligible or
      ineligible for clinical trials. Design, Setting, and Participants: An
      observational study using 157 dermatology centers in the United Kingdom and
      Republic of Ireland was carried out wherein we applied the eligibility criteria
      of clinical trials of biologic therapies for psoriasis to patients who were being
      followed up in the British Association of Dermatologists Biologic Interventions
      Register (BADBIR) and being prescribed biologics as part of standard clinical
      care. Patients with psoriasis registered to BADBIR who were taking etanercept
      (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with
      at least 1 follow-up visit. Eligibility criteria were extracted from phase 3
      licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of
      moderate to severe psoriasis. Patients in BADBIR with a missing baseline
      Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10
      (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be
      eligible were investigated separately. Eligibility categories applied to BADBIR
      included: eligible, ineligible, insufficient baseline PASI only, and missing
      baseline PASI only. Main Outcomes and Measures: (1) Drug discontinuation:
      cumulative incidence at 12 months by stop reason per eligibility category and
      drug; (2) effectiveness: linear regression of absolute change in PASI from
      baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12
      months between eligibility categories per drug. Results: The mean (SD) age of the
      7136 patients included in the analysis was 45 (13) years and 2924 (41%) were
      women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%)
      adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible.
      The most common reasons for ineligibility were diabetes (etanercept, 143 [9%];
      ustekinumab, 201 [12%]) and nonchronic plaque psoriasis (adalimumab, 157 [4%]).
      Patients categorized as ineligible (etanercept, 367 [24%]; adalimumab, 282 [7%];
      ustekinumab, 394 [24%]) achieved a smaller absolute change in PASI after 6 and 12
      months (adalimumab, ustekinumab), and had significantly higher rates of SAEs
      compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6;
      adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8).
      No significant differences in drug discontinuation were observed between
      categories. Conclusions and Relevance: Clinical trial effectiveness and safety
      outcomes are not representative of real-world patients in BADBIR patients
      categorized as ineligible for such trials.

PMID- 29590280
TI  - The Emerging Clinical Neuroscience of Autism Spectrum Disorder: A Review.
AB  - Importance: Autism spectrum disorder (ASD) is a highly prevalent disorder, and
      community psychiatrists are likely to treat many individuals with ASD during
      their clinical practice. This clinical case challenge describes a routine
      evaluation of irritability and self-injury in a preschool-aged child who meets
      the criteria for ASD. The case also illustrates the importance of known risk
      factors for ASD, such as chromosomal deletion and prematurity. This clinical
      neuroscience article seeks to educate the clinician of current avenues of
      research that can inform and may already affect clinical practice for this
      patient, while providing a preview of research that may yield biological
      treatments for ASD within the next decade. Observations: A diagnosis of ASD is
      defined behaviorally; therefore, many genetic and environmental risk factors,
      working singly or in concert, are linked to ASD. The prenatal period of brain
      development is particularly sensitive to risk factors such as gene mutation or
      drug exposure that affect brain development and circuitry formation. Currently,
      neuroimaging researchers can detect changes in brain connectivity of children
      with ASD as young as 6 months, followed by an atypical trajectory of brain
      development through preschool age and ongoing connectivity inefficiencies across
      the lifespan. Animal and cellular model systems have provided a means for
      defining the molecular and cellular changes associated with risk factors for ASD.
      The ability to connect specific treatments to particular subgroups of people with
      ASD is the defining hope of precision medicine initiatives. Conclusions and
      Relevance: The advent of next-generation sequencing technology, advanced imaging
      techniques, and cutting-edge molecular techniques for modeling ASD has allowed
      researchers to define ASD risk-related biological pathways and circuits that may,
      for the first time, unify the effects of disparate risk factors into common
      neurobiological mechanisms. The path from these mechanisms to biological
      treatments that improve the lives of individuals with autism remains unclear, but
      the cumulative output of multiple lines of research suggests that subtyping by
      genetic risk factors may be a particularly tractable way to capitalize on
      individual differences amenable to specific treatments.

PMID- 29590282
TI  - Complete vs Incomplete Revascularization During Percutaneous Coronary
      Intervention and Improved Survival-The Key Is Immortality.

PMID- 29590281
TI  - Association of Childhood Irritability and Depressive/Anxious Mood Profiles With
      Adolescent Suicidal Ideation and Attempts.
AB  - Importance: Suicidal ideation and suicide attempt (suicidality) are common in
      adolescence and a public health concern. Childhood depression is a key risk
      factor for later suicidality and often co-occurs with irritability. No study to
      date has examined the joint association of depressive mood and irritability
      during childhood with later suicidality. Objective: To investigate the
      association of childhood irritability and depressive/anxious mood profiles with
      adolescent suicidality. Design, Setting, and Participants: This population-based
      cohort study included 1430 participants in the Quebec Longitudinal Study of Child
      Development. Participants underwent assessment yearly or bi-yearly (5 months to
      17 years). Data were collected from March 16, 1998, through July 17, 2015.
      Exposures: Profiles defined by the joint developmental trajectories of
      irritability and depressive/anxious mood at 6 to 12 years of age. Main Outcomes
      and Measures: Self-reported past-year suicidality (ie, serious suicidal ideation
      or suicide attempt) at 13, 15, and 17 years of age. Irritability and
      depressive/anxious mood were assessed using teacher report 5 times from 6 to 12
      years of age. Results: The study included 1430 participants (676 boys [47.3%] and
      754 girls [52.7%]) followed up to 17 years of age. Group-based multitrajectory
      modeling identified the following profiles: combined no irritability and low
      depressive/anxious mood with low irritability and low depressive/anxious mood
      (831 [58.1%]; reference group), moderate irritability and low depressive/anxious
      mood (353 [24.7%]), high depressive/anxious mood only (94 [6.6%]), and high
      irritability and depressive/anxious mood (152 [10.6%]). Children with high
      irritability and high depressive/anxious mood reported higher rates of
      suicidality (25 of 152 [16.4%]) compared with the group with the lowest symptom
      levels (91 of 831 [11.0%]). In logistic regression analyses, the high
      irritability and depressive/anxious mood profile (odds ratio [OR], 2.22; 95% CI,
      1.32-3.74; number needed to be exposed [NNE], 18) was associated with
      suicidality. To a lesser extent, the moderate irritability and low
      depressive/anxious mood profile was also associated with suicidality (OR, 1.51;
      95% CI, 1.02-2.25; NNE = 48). The high depressive/anxious mood only profile was
      not associated with later suicidality (OR, 0.96; 95% CI, 0.47-1.95; NNE = -320).
      The high irritability and depressive/anxious mood profile was associated with a
      higher suicidal risk compared with the depressive/anxious mood only profile (OR,
      2.28; 95% CI, 1.02-5.15). Girls with the high irritability and high
      depressive/anxious mood profile had higher risk for suicidality (OR, 3.07; 95%
      CI, 1.54-6.12; NNE = 5). Conclusions and Relevance: Children with high
      irritability and depressive/anxious mood and, to a lesser extent, with moderate
      irritability only had a higher suicidal risk during adolescence compared with
      children with low symptom levels. Early manifestation of chronic irritability
      during childhood, especially when combined with depressive/anxious mood, may be
      associated with an elevated risk for adolescent suicidality. The putatively
      causal role of irritability should be investigated.

PMID- 29590283
TI  - Complete vs Incomplete Revascularization During Percutaneous Coronary
      Intervention and Improved Survival-The Key Is Immortality-Reply.

PMID- 29590284
TI  - Paucity of Lesbian, Gay, Bisexual, and Transgender Health-Related Content in the
      Basic Dermatology Curriculum.

PMID- 29590285
TI  - Errors in Figure 3 and Affiliations.

PMID- 29590286
TI  - Defining Postoperative Opioid Needs Among Preoperative Opioid Users.

PMID- 29590287
TI  - Robert Kerns, PhD: Researching Nondrug Approaches to Pain Management.

PMID- 29590288
TI  - Depression Screening in Dermatology-Think Isotretinoin.

PMID- 29590290
TI  - The 2017 AHA/ACC Performance and Quality Measures for Patients With Acute
      Myocardial Infarction.

PMID- 29590289
TI  - Associations of Bariatric Surgery With Changes in Interpersonal Relationship
      Status: Results From 2 Swedish Cohort Studies.
AB  - Importance: Bariatric surgery is a life-changing treatment for patients with
      severe obesity, but little is known about its association with interpersonal
      relationships. Objectives: To investigate if relationship status is altered after
      bariatric surgery. Design, Setting, and Participants: Changes in relationship
      status after bariatric surgery were examined in 2 cohorts: (1) the prospective
      Swedish Obese Subjects (SOS) study, which recruited patients undergoing bariatric
      surgery from September 1, 1987, to January 31, 2001, and compared their care with
      usual nonsurgical care in matched obese control participants; and (2)
      participants from the Scandinavian Obesity Surgery Registry (SOReg), a
      prospective, electronically captured register that recruited patients from
      January 2007 through December 2012 and selected comparator participants from the
      general population matched on age, sex, and place of residence. Data was
      collected in surgical departments and primary health care centers in Sweden. The
      current analysis includes data collected up until July 2015 (SOS) and December
      2012 (SOReg). Data analysis was completed from June 2016 to December 2017. Main
      Outcomes and Measures: In the SOS study, information on relationship status was
      obtained from questionnaires. In the SOReg and general population cohort,
      information on marriage and divorce was obtained from the Swedish Total
      Population Registry. Results: The SOS study included 1958 patients who had
      bariatric surgery (of whom 1389 [70.9%] were female) and 1912 matched obese
      controls (of whom 1354 [70.8%] were female) and had a median (range) follow-up of
      10 (0.5-20) years. The SOReg cohort included 29 234 patients who had gastric
      bypass surgery (of whom 22 131 [75.6%] were female) and 283 748 comparators from
      the general population (of whom 214 342 [75.5%] were female), and had a median
      (range) follow-up of 2.9 (0.003-7.0) years. In the SOS study, the surgical
      patients received gastric banding (n = 368; 18.8%), vertical banded gastroplasty
      (n = 1331; 68.0%), or gastric bypass (n = 259; 13.2%); controls received usual
      obesity care. In SOReg, all 29 234 surgical participants received gastric bypass
      surgery. In the SOS study, bariatric surgery was associated with increased
      incidence of divorce/separation compared with controls for those in a
      relationship (adjusted hazard ratio [aHR] = 1.28; 95% CI, 1.03-1.60; P = .03) and
      increased incidence of marriage or new relationship (aHR = 2.03; 95% CI, 1.52
      2.71; P < .001) in those who were unmarried or single at baseline. In the SOReg
      and general population cohort, gastric bypass was associated with increased
      incidence of divorce compared with married control participants (aHR = 1.41; 95%
      CI, 1.33-1.49; P < .001) and increased incidence of marriage in those who were
      unmarried at baseline (aHR = 1.35; 95% CI, 1.28-1.42; P < .001). Within the
      surgery groups, changes in relationship status were more common in those with
      larger weight loss. Conclusions and Relevance: In addition to its association
      with obesity comorbidities, bariatric surgery-induced weight loss is also
      associated with changes in relationship status.

PMID- 29590291
TI  - Near-Infrared Sentinel Lymph Node Identification in Non-Small Cell Lung Cancer.

PMID- 29590292
TI  - Solitary Asymptomatic Tumor in the Axilla.

PMID- 29590293
TI  - Considerations for Randomized Controlled Trials During Future Filovirus
      Outbreaks.

PMID- 29590294
TI  - Leveraging known genomic variants to improve detection of variants, especially
      close-by Indels.
AB  - Motivation: The detection of genomic variants has great significance in genomics,
      bioinformatics, biomedical research and its applications. However, despite a lot
      of effort, Indels and structural variants are still under-characterized compared
      to SNPs. Current approaches based on next-generation sequencing data usually
      require large numbers of reads (high coverage) to be able to detect such types of
      variants accurately. However Indels, especially those close to each other, are
      still hard to detect accurately. Results: We introduce a novel approach that
      leverages known variant information, e.g. provided by dbSNP, dbVar, ExAC or the
      1000 Genomes Project, to improve sensitivity of detecting variants, especially
      close-by Indels. In our approach, the standard reference genome and the known
      variants are combined to build a meta-reference, which is expected to be
      probabilistically closer to the subject genomes than the standard reference. An
      alignment algorithm, which can take into account known variant information, is
      developed to accurately align reads to the meta-reference. This strategy resulted
      in accurate alignment and variant calling even with low coverage data. We showed
      that compared to popular methods such as GATK and SAMtools, our method
      significantly improves the sensitivity of detecting variants, especially Indels
      that are close to each other. In particular, our method was able to call these
      close-by Indels at a 15-20% higher sensitivity than other methods at low
      coverage, and still get 1-5% higher sensitivity at high coverage, at competitive
      precision. These results were validated using simulated data with variant
      profiles extracted from the 1000 Genomes Project data, and real data from the
      Illumina Platinum Genomes Project and ExAC database. Our finding suggests that by
      incorporating known variant information in an appropriate manner, sensitive
      variant calling is possible at a low cost. Availability and implementation:
      Implementation can be found in our public code repository
      https://github.com/namsyvo/IVC. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29590295
TI  - Functional annotation of genomic variants in studies of late-onset Alzheimer's
      disease.
AB  - Motivation: Annotation of genomic variants is an increasingly important and
      complex part of the analysis of sequence-based genomic analyses. Computational
      predictions of variant function are routinely incorporated into gene-based
      analyses of rare-variants, though to date most studies use limited information
      for assessing variant function that is often agnostic of the disease being
      studied. Results: In this work, we outline an annotation process motivated by the
      Alzheimer's Disease Sequencing Project, illustrate the impact of including tissue
      specific transcript sets and sources of gene regulatory information and assess
      the potential impact of changing genomic builds on the annotation process. While
      these factors only impact a small proportion of total variant annotations (~5%),
      they influence the potential analysis of a large fraction of genes (~25%).
      Availability and implementation: Individual variant annotations are available via
      the NIAGADS GenomicsDB, at https://www.niagads.org/genomics/ tools-and
      software/databases/genomics-database. Annotations are also available for bulk
      download at https://www.niagads.org/datasets. Annotation processing software is
      available at http://www.icompbio.net/resources/software-and-downloads/.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29590298
TI  - Relationship Status After Bariatric Surgery: It's Complicated.

PMID- 29590297
TI  - Deep learning improves antimicrobial peptide recognition.
AB  - Motivation: Bacterial resistance to antibiotics is a growing concern.
      Antimicrobial peptides (AMPs), natural components of innate immunity, are popular
      targets for developing new drugs. Machine learning methods are now commonly
      adopted by wet-laboratory researchers to screen for promising candidates.
      Results: In this work, we utilize deep learning to recognize antimicrobial
      activity. We propose a neural network model with convolutional and recurrent
      layers that leverage primary sequence composition. Results show that the proposed
      model outperforms state-of-the-art classification models on a comprehensive
      dataset. By utilizing the embedding weights, we also present a reduced-alphabet
      representation and show that reasonable AMP recognition can be maintained using
      nine amino acid types. Availability and implementation: Models and datasets are
      made freely available through the Antimicrobial Peptide Scanner vr.2 web server
      at www.ampscanner.com. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29590299
TI  - Commentary on: Plasma Activation of a Breast Implant Shell in Conjunction With
      Antibacterial Irrigants Enhances Antibacterial Activity.

PMID- 29590300
TI  - Amyotrophic lateral sclerosis and exposure to diesel exhaust in a Danish cohort.
AB  - Previous studies have suggested an increased risk of amyotrophic lateral
      sclerosis (ALS) and other motor neuron diseases for those in occupations commonly
      exposed to diesel exhaust (DE). In this study, we investigated the association
      between occupational exposures to DE and odds of ALS. ALS cases were identified
      from the Danish National Patient Registry 1982 to 2013 and individually matched
      to 100 controls per case based on birth year and sex. Using occupational history
      since 1964 from the Danish Pension Fund, Cumulative DE exposures were estimated
      using a job exposure matrix. Associations were evaluated using conditional
      logistic regression analyses and stratified by sex. DE exposure at 10-year lag
      periods was positively associated with ALS in men ever exposed (aOR: 1.20; 95%
      CI: 1.05, 1.38). For men with > 50% probability of DE exposure, we observed a
      positive association with ALS and the highest quartile exposures during the 5
      year lag period (aOR: 1.40; 95% CI: 1.11, 1.78) and 10-year lag period (aOR:
      1.41; 95% CI: 1.11, 1.79). Our study suggests an association between consistently
      higher exposures to DE and ALS in men but not in women. These findings support
      those of previously reported associations between ALS and commonly DE exposed
      occupations.

PMID- 29590301
TI  - GENEASE: real time bioinformatics tool for multi-omics and disease ontology
      exploration, analysis and visualization.
AB  - Motivation: Advances in high-throughput sequencing technologies have made it
      possible to generate multiple omics data at an unprecedented rate and scale. The
      accumulation of these omics data far outpaces the rate at which biologists can
      mine and generate new hypothesis to test experimentally. There is an urgent need
      to develop a myriad of powerful tools to efficiently and effectively search and
      filter these resources to address specific post-GWAS functional genomics
      questions. However, to date, these resources are scattered across several
      databases and often lack a unified portal for data annotation and analytics. In
      addition, existing tools to analyze and visualize these databases are highly
      fragmented, resulting researchers to access multiple applications and manual
      interventions for each gene or variant in an ad hoc fashion until all the
      questions are answered. Results: In this study, we present GENEASE, a web-based
      one-stop bioinformatics tool designed to not only query and explore multi-omics
      and phenotype databases (e.g. GTEx, ClinVar, dbGaP, GWAS Catalog, ENCODE, Roadmap
      Epigenomics, KEGG, Reactome, Gene and Phenotype Ontology) in a single web
      interface but also to perform seamless post genome-wide association downstream
      functional and overlap analysis for non-coding regulatory variants. GENEASE
      accesses over 50 different databases in public domain including model organism
      specific databases to facilitate gene/variant and disease exploration, enrichment
      and overlap analysis in real time. It is a user-friendly tool with point-and
      click interface containing links for support information including user manual
      and examples. Availability and implementation: GENEASE can be accessed freely at
      http://research.cchmc.org/mershalab/GENEASE/login.html. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29590302
TI  - Surfactant protein A suppresses preterm delivery induced by live Escherichia coli
      in mice.
AB  - Preterm birth accounts for the majority of neonatal morbidity and mortality in
      the developed world. A significant proportion of cases of spontaneous preterm
      labor are attributable to infections within gestational tissues. Surfactant
      protein A (SP-A), a collectin produced in the fetal lung and other tissues, has
      been shown previously in mice to suppress preterm delivery due to intrauterine
      (IU) instillation of sterile proinflammatory substances. Here we report a
      powerful antilabor effect for SP-A after IU infection with live Escherichia coli.
      SP-A abolished preterm birth (rate reduced from 100% to 0%) when it was
      administered into the uterus simultaneously with bacterial infection, reducing it
      by 75% when administered intravenously at the same time as IU bacterial
      inoculation, and by 48% when administered intravenously 4 h after IU bacterial
      infection. This effect on preterm delivery was accompanied by a parallel benefit
      on fetal survival in utero. SP-A had no effect on bacterial growth but reversed
      several major consequences of infection, including increased production of
      inflammatory mediators and a shift in macrophage polarization to the M1
      phenotype. These findings suggest that exogenous SP-A has potential use to
      counteract infection-induced labor by reversing its proinflammatory consequences.

PMID- 29590303
TI  - SPV: a JavaScript Signaling Pathway Visualizer.
AB  - Summary: The visualization of molecular interactions annotated in web resources
      is useful to offer to users such information in a clear intuitive layout. These
      interactions are frequently represented as binary interactions that are laid out
      in free space where, different entities, cellular compartments and interaction
      types are hardly distinguishable. Signaling Pathway Visualizer is a free open
      source JavaScript library, which offers a series of pre-defined elements,
      compartments and interaction types meant to facilitate the representation of
      signaling pathways consisting of causal interactions without neglecting simple
      protein-protein interaction networks. Availability and implementation: Freely
      available under Apache version 2 license; Source code:
      https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language:
      JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js.

PMID- 29590305
TI  - Interactive and coordinated visualization approaches for biological data
      analysis.
AB  - The field of computational biology has become largely dependent on data
      visualization tools to analyze the increasing quantities of data gathered through
      the use of new and growing technologies. Aside from the volume, which often
      results in large amounts of noise and complex relationships with no clear
      structure, the visualization of biological data sets is hindered by their
      heterogeneity, as data are obtained from different sources and contain a wide
      variety of attributes, including spatial and temporal information. This requires
      visualization approaches that are able to not only represent various data
      structures simultaneously but also provide exploratory methods that allow the
      identification of meaningful relationships that would not be perceptible through
      data analysis algorithms alone. In this article, we present a survey of
      visualization approaches applied to the analysis of biological data. We focus on
      graph-based visualizations and tools that use coordinated multiple views to
      represent high-dimensional multivariate data, in particular time series gene
      expression, protein-protein interaction networks and biological pathways. We then
      discuss how these methods can be used to help solve the current challenges
      surrounding the visualization of complex biological data sets.

PMID- 29590304
TI  - Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation
      After Coronary Artery Bypass Graft Surgery and Patients With Nonvalvular Atrial
      Fibrillation.
AB  - Importance: New-onset postoperative atrial fibrillation (POAF) is a common
      complication of coronary artery bypass graft (CABG) surgery. However, the long
      term risk of thromboembolism in patients who develop POAF after CABG surgery
      remains unknown. In addition, information on stroke prophylaxis in this setting
      is lacking. Objective: To examine stroke prophylaxis and the long-term risk of
      thromboembolism in patients with new-onset POAF after first-time isolated CABG
      surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation
      (NVAF). Design, Setting, and Participants: This cohort study used data from a
      clinical cardiac surgery database and Danish nationwide registries to identify
      patients undergoing first-time isolated CABG surgery who developed new-onset POAF
      from January 1, 2000, through June 30, 2015. These patients were matched by age,
      sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF
      in a 1 to 4 ratio. Data analysis was completed from February 2017 to January
      2018. Main Outcomes and Measures: The proportion of patients initiating oral
      anticoagulation therapy within 30 days and the rates of thromboembolism. Results:
      A total of 2108 patients who developed POAF after CABG surgery were matched with
      8432 patients with NVAF. In the full population of 10 540 patients, the median
      (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were
      men. Oral anticoagulation therapy was initiated within 30 days postdischarge in
      175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of
      thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7
      events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55
      0.81; P < .001). Anticoagulation therapy during follow-up was associated with a
      lower risk of thromboembolic events in both patients with POAF (adjusted HR,
      0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68;
      P < .001) compared with patients who did not receive any anticoagulation therapy.
      Further, the risk of thromboembolism was not significantly higher in patients
      with POAF compared with those who did not develop POAF after CABG surgery
      (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). Conclusions and Relevance: New
      onset POAF in patients who had undergone CABG surgery was associated with a lower
      long-term thromboembolic risk than that of patients who had NVAF. These data do
      not support the notion that new-onset POAF should be regarded as equivalent to
      primary NVAF in terms of long-term thromboembolic risk.

PMID- 29590306
TI  - Novel Proteomic Assay of Breast Implants Reveals Proteins With Significant
      Binding Differences: Implications for Surface Coating and Biocompatibility.
AB  - Background: Silicone elastomer, a ubiquitous biomaterial and main constituent of
      breast implants, has been used for breast augmentation and reconstruction for
      over 50 years. Breast implants have direct local and purported systemic effects
      on normal tissue homeostasis dictated by the chemical and physical presence of
      the implant. Objectives: Protein adsorption has been demonstrated to be a key
      driver of local reactions to silicone. We sought to develop an assay and identify
      the proteins that coat implants during breast implantation. Methods: Wound fluid
      was salvaged from women who had undergone breast reduction and incubated in
      contact with the surface of 13 commercially available implant surfaces. An in
      situ digestion technique was optimized to elute bound proteins. Samples were
      analyzed on an Orbitrap elite analyser, proteins identified in Mascot Demon and
      analyzed in Progenesis. Results: A total of 822 proteins were identified, bound
      to the surfaces of the implants. Extracellular proteins were the most abundant
      ontology, followed by intracellular proteins. Fibrinogen, a proinflammatory
      protein and Albumin, an anti-inflammatory protein had significant (P < 0.0001)
      binding differences between the surfaces studied. Complement C3, C5, and factor H
      were also shown to have significantly different binding affinities for the
      implants included in the study (P < 0.05). Conclusions: We have developed a novel
      assay of breast implant protein binding and demonstrated significant binding
      affinities for relevant proteins derived from breast tissue wound fluid. Level of
      Evidence 5: 

PMID- 29590308
TI  - Comparing Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic
      Pressure for Assessment of Left-Sided Filling Pressures.

PMID- 29590307
TI  - Mutations causing specific arrests in the development of mouse primordial germ
      cells and gonocytes.
AB  - This review focuses on those mouse mutations that cause an effect on the
      morphology, viability, and/or behavior of primordial germ cells (PGCs) and
      gonocytes at specific steps of their fetal development up to the start of
      spermatogenesis, a few days after birth. To restrict the area covered, mice with
      mutations that cause abnormal hormone levels or mutations of genes not expressed
      in germ cells that secondarily cause spermatogenic problems are not discussed. To
      make our literature search as comprehensive as possible, Pubmed was searched for
      "(primordial germ cells OR prospermatogonia OR prespermatogonia OR gonocytes OR
      spermatogonia or meiosis or spermiogenesis or spermatogenesis) AND mouse AND
      (knockout or mutant or transgenic)." This search started at 2003 as mutants
      created earlier were already retrieved for a previous review. The resulting
      citations were then further selected for complete or partial arrests at the level
      of PGCs and/or gonocytes. Fifty-nine protein coding genes and two miRNA coding
      genes were found that arrest the development of PGCs and gonocytes at specific
      steps providing a better insight into the regulation of the development of these
      cells. As to be expected, often problems in fetal germ cell development have an
      effect on the fertility of the mice at adulthood.

PMID- 29590309
TI  - Generalizing biomedical relation classification with neural adversarial domain
      adaptation.
AB  - Motivation: Creating large datasets for biomedical relation classification can be
      prohibitively expensive. While some datasets have been curated to extract protein
      protein and drug-drug interactions (PPIs and DDIs) from text, we are also
      interested in other interactions including gene-disease and chemical-protein
      connections. Also, many biomedical researchers have begun to explore ternary
      relationships. Even when annotated data are available, many datasets used for
      relation classification are inherently biased. For example, issues such as sample
      selection bias typically prevent models from generalizing in the wild. To address
      the problem of cross-corpora generalization, we present a novel adversarial
      learning algorithm for unsupervised domain adaptation tasks where no labeled data
      are available in the target domain. Instead, our method takes advantage of
      unlabeled data to improve biased classifiers through learning domain-invariant
      features via an adversarial process. Finally, our method is built upon recent
      advances in neural network (NN) methods. Results: We experiment by extracting
      PPIs and DDIs from text. In our experiments, we show domain invariant features
      can be learned in NNs such that classifiers trained for one interaction type
      (protein-protein) can be re-purposed to others (drug-drug). We also show that our
      method can adapt to different source and target pairs of PPI datasets. Compared
      to prior convolutional and recurrent NN-based relation classification methods
      without domain adaptation, we achieve improvements as high as 30% in F1-score.
      Likewise, we show improvements over state-of-the-art adversarial methods.
      Availability and implementation: Experimental code is available at
      https://github.com/bionlproc/adversarial-relation-classification. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29590310
TI  - Mouse oocytes connect with granulosa cells by fusing with cell membranes and form
      a large complex during follicle development.
AB  - Proper development and maturation of oocytes requires interaction with granulosa
      cells. Previous reports have indicated that mammalian oocytes connect with
      cumulus cells through gap junctions at the tip of transzonal projections that
      extend from the cells. Although the gap junctions between oocytes and transzonal
      projections provide a pathway through which small molecules (<1 kDa) can travel,
      it is unclear how molecules >1 kDa are transported between the oocytes and
      cumulus cells. In this study, we presented new connections between oocytes and
      granulosa cells. The green fluorescein protein Aequorea coerulescens green
      fluorescein protein (AcGFP1) localizing in oocyte cell membrane, 1,1'-dioctadecyl
      3,3,3',3'-tetramethylindocarbocyanine perchlorate and dextran conjugates (10,000
      MW) injected into the oocytes, which were unable to pass through gap junctions,
      were diffused from the oocytes into the surrounding granulosa cells through these
      connections. These connect an oocyte to the surrounding cumulus and granulosa
      cells by fusing with the cell membranes and forming a large complex during
      follicle development. Furthermore, we show two characteristics of these
      connections during follicle development-the localization of growth and
      differentiation factor-9 within the connections and the dynamics of the
      connections at ovulation. This article presents for the first time that mammalian
      oocytes directly connect to granulosa cells by fusing with the cell membrane,
      similar to that in Drosophila.

PMID- 29590312
TI  - Reply to Collins and Riley.

PMID- 29590311
TI  - Primaquine Pharmacokinetics in Lactating Women and Breastfed Infant Exposures.
AB  - Background: Primaquine is the only drug providing radical cure of Plasmodium
      vivax malaria. It is not recommended for breastfeeding women as it causes
      hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, and
      breast milk excretion and thus infant exposure are not known. Methods: Healthy
      G6PD-normal breastfeeding women with previous P. vivax infection and their
      healthy G6PD-normal infants between 28 days and 2 years old were enrolled.
      Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and
      carboxyprimaquine concentrations were measured in maternal venous plasma,
      capillary plasma, and breast milk samples and infant capillary plasma samples
      taken on days 0, 3, 7, and 13. Results: In 20 mother-infant pairs, primaquine
      concentrations were below measurement thresholds in all but 1 infant capillary
      plasma sample (that contained primaquine 2.6 ng/mL), and carboxyprimaquine was
      likewise unmeasurable in the majority of infant samples (maximum value 25.8
      ng/mL). The estimated primaquine dose received by infants, based on measured
      breast milk levels, was 2.98 ug/kg/day (ie, ~0.6% of a hypothetical infant daily
      dose of 0.5 mg/kg). There was no evidence of drug-related hemolysis in the
      infants. Maternal levels were comparable to levels in nonlactating patients, and
      adverse events in mothers were mild. Conclusions: The concentrations of
      primaquine in breast milk are very low and therefore very unlikely to cause
      adverse effects in the breastfeeding infant. Primaquine should not be withheld
      from mothers breastfeeding infants or young children. More information is needed
      in neonates. Clinical Trials Registration: NCT01780753.

PMID- 29590313
TI  - Follow-Up Data Improve the Estimation of the Prevalence of Heavy Alcohol
      Consumption.
AB  - Aims: We aim to adjust for potential non-participation bias in the prevalence of
      heavy alcohol consumption. Methods: Population survey data from Finnish health
      examination surveys conducted in 1987-2007 were linked to the administrative
      registers for mortality and morbidity follow-up until end of 2014. Utilising
      these data, available for both participants and non-participants, we model the
      association between heavy alcohol consumption and alcohol-related disease
      diagnoses. Results: Our results show that the estimated prevalence of heavy
      alcohol consumption is on average of 1.5 times higher for men and 1.8 times
      higher for women than what was obtained from participants only (complete case
      analysis). The magnitude of the difference in the mean estimates by year varies
      from 0 to 9 percentage points for men and from 0 to 2 percentage points for
      women. Conclusion: The proposed approach improves the prevalence estimation but
      requires follow-up data on non-participants and Bayesian modelling.

PMID- 29590314
TI  - Altruistic decisions following penetrating traumatic brain injury.
AB  - The cerebral correlates of altruistic decisions have increasingly attracted the
      interest of neuroscientists. To date, investigations on the neural underpinnings
      of altruistic decisions have primarily been conducted in healthy adults
      undergoing functional neuroimaging as they engaged in decisions to punish third
      parties. The chief purpose of the present study was to investigate altruistic
      decisions following focal brain damage with a novel altruistic decision task. In
      contrast to studies that have focused either on altruistic punishment or
      donation, the Altruistic Decision Task allows players to anonymously punish or
      donate to 30 charitable organizations involved with salient societal issues such
      as abortion, nuclear energy and civil rights. Ninety-four Vietnam War veterans
      with variable patterns of penetrating traumatic brain injury and 28 healthy
      veterans who also served in combat participated in the study as normal controls.
      Participants were asked to invest $1 to punish or reward real societal
      organizations, or keep the money for themselves. Associations between lesion
      distribution and performance on the task were analysed with multivariate support
      vector regression, which enables the assessment of the joint contribution of
      multiple regions in the determination of a given behaviour of interest. Our main
      findings were: (i) bilateral dorsomedial prefrontal lesions increased altruistic
      punishment, whereas lesions of the right perisylvian region and left temporo
      insular cortex decreased punishment; (ii) altruistic donations were increased by
      bilateral lesions of the dorsomedial parietal cortex, whereas lesions of the
      right posterior superior temporal sulcus and middle temporal gyri decreased
      donations; (iii) altruistic punishment and donation were only weakly correlated,
      emphasizing their dissociable neuroanatomical associations; and (iv) altruistic
      decisions were not related to post-traumatic personality changes. These findings
      indicate that altruistic punishment and donation are determined by largely non
      overlapping cerebral regions, which have previously been implicated in social
      cognition and moral experience such as evaluations of intentionality and
      intuitions of justice and
      morality.10.1093/brain/awy064_video1awy064media15758316955001.

PMID- 29590316
TI  - 'No, the government doesn't need to, it's already self-regulated': a qualitative
      study among vape shop operators on perceptions of electronic vapor product
      regulation.
AB  - While the market share of electronic vapor products (EVPs), sold primarily
      through vape shops and other outlets, has increased rapidly, these products
      remained largely unregulated until 2016. This study, conducted prior to
      announcement of the deeming regulations, provides insights into vape shop
      operator attitudes toward potential government regulations of EVPs. In 2015, we
      conducted 37 in-person interviews of vape shop operators across nine US cities.
      Shops were identified through extensive web-searches. We used QSR International's
      NVivo 11 qualitative data analysis software to analyze the transcripts. Many vape
      shop operators viewed regulations requiring safe production of e-liquids, child
      resistant bottles and listing e-juice ingredients as acceptable. They disagreed
      with the elimination of free samples and bans on flavored e-liquid sales, which
      generate significant revenue for their stores. Many held negative perceptions of
      pre-market review of new product lines and EVP-specific taxes. All agreed that
      EVPs should not be sold to minors, but most felt that owners should not be fined
      if minors visited vape shops. Findings from this study offer insights into the
      acceptability of proposed regulations, as well as barriers to effective
      regulation implementation.

PMID- 29590317
TI  - Alteration of transporter activities in the epididymides of infertile initial
      segment-specific Pten knockout mice.
AB  - A fully functional initial segment, the most proximal region of the epididymis,
      is important for male fertility. Our previous study generated a mouse model to
      investigate the importance of initial segment function in male fertility. In that
      model, phosphatase and tensin homolog (Pten) was conditionally removed from the
      initial segment epithelium, which resulted in epithelial de-differentiation. When
      spermatozoa progressed through the de-differentiated epithelial duct, they
      developed angled flagella, suggesting compromised sperm maturation, which
      eventually resulted in male infertility. To understand the molecular mechanisms,
      by which PTEN regulates epididymal sperm maturation, we compared the
      transcriptome profile of the initial segment between controls and initial segment
      specific Pten knockouts and revealed that water, ion, and organic solute
      transporter activities were one of the top molecular and cellular functions
      altered following loss of Pten. Alteration in protein levels and localization of
      several transporters following loss of Pten were also observed by
      immunofluorescence analysis. Epithelial cells of the initial segment from
      knockouts were more permeable to fluorescein isothiocyanate-dextran (4000 Da)
      compared to controls. Interestingly, conditional deletion of Pten from other
      organs also resulted in changes in transporter activity, suggesting a common role
      of PTEN in regulation of transporter activity. Taken together, our data support
      the hypothesis that loss of Pten from the initial segment epithelium results in
      changes in the transporting and permeability characteristics of the epithelium,
      which in turn altered the luminal fluid microenvironment that is so important for
      sperm maturation and male fertility.

PMID- 29590315
TI  - Association of Brain Cortical Changes With Relapse in Patients With Major
      Depressive Disorder.
AB  - Importance: More than half of all patients with major depressive disorder (MDD)
      experience a relapse within 2 years after recovery. It is unclear how relapse
      affects brain morphologic features during the course of MDD. Objective: To use
      structural magnetic resonance imaging to identify morphologic brain changes
      associated with relapse in MDD. Design, Setting, and Participants: In this
      longitudinal case-control study, patients with acute MDD at baseline and healthy
      controls were recruited from the University of Munster Department of Psychiatry
      from March 21, 2010, to November 14, 2014, and were reassessed from November 11,
      2012, to October 28, 2016. Depending on patients' course of illness during follow
      up, they were subdivided into groups of patients with and without relapse. Whole
      brain gray matter volume and cortical thickness of the anterior cingulate cortex,
      orbitofrontal cortex, middle frontal gyrus, and insula were assessed via 3-T
      magnetic resonance imaging at baseline and 2 years later. Main Outcomes and
      Measures: Gray matter was analyzed via group (no relapse, relapse, and healthy
      controls) by time (baseline and follow-up) analysis of covariance, controlling
      for age and total intracranial volume. Confounding factors of medication and
      depression severity were assessed. Results: This study included 37 patients with
      MDD and a relapse (19 women and 18 men; mean [SD] age, 37.0 [12.7] years), 23
      patients with MDD and without relapse (13 women and 10 men; mean [SD] age, 32.5
      [10.5] years), and 54 age- and sex-matched healthy controls (24 women and 30 men;
      mean [SD] age, 37.5 [8.7] years). A significant group-by-time interaction
      controlling for age and total intracranial volume revealed that patients with
      relapse showed a significant decline of insular volume (difference, -0.032; 95%
      CI, -0.063 to -0.002; P = .04) and dorsolateral prefrontal volume (difference, 
      0.079; 95% CI, -0.113 to -0.045; P < .001) from baseline to follow-up. In
      patients without relapse, gray matter volume in these regions did not change
      significantly (insula: difference, 0.027; 95% CI, -0.012 to 0.066; P = .17; and
      dorsolateral prefrontal volume: difference, 0.023; 95% CI, -0.020 to 0.066; P =
      .30). Volume changes were not correlated with psychiatric medication or with
      severity of depression at follow-up. Additional analysis of cortical thickness
      showed an increase in the anterior cingulate cortex (difference, 0.073 mm; 95%
      CI, 0.023-0.123 mm; P = .005) and orbitofrontal cortex (difference, 0.089 mm; 95%
      CI, 0.032-0.147 mm; P = .003) from baseline to follow-up in patients without
      relapse. Conclusion and Relevance: A distinct association of relapse in MDD with
      brain morphologic features was revealed using a longitudinal design. Relapse is
      associated with brain structures that are crucial for regulation of emotions and
      thus needs to be prevented. This study might be a step to guide future prognosis
      and maintenance treatment in patients with recurrent MDD.

PMID- 29590319
TI  - Defining Postoperative Opioid Needs Among Preoperative Opioid Users-Reply.

PMID- 29590320
TI  - The evil of the patent foramen ovale: we are seeing but the tip of the iceberg.

PMID- 29590318
TI  - Intestinal Barrier Dysfunction and Microbial Translocation in Human
      Immunodeficiency Virus-Infected Pregnant Women Are Associated With Preterm Birth.
AB  - Background: Preterm birth (PTB) rates are high in human immunodeficiency virus
      (HIV)-infected populations, even when on treatment. Still, only a subset of all
      births in HIV-infected pregnant women result in PTB, suggesting that risk factors
      other than HIV infection itself are also important. Inflammation is a known risk
      factor in uninfected populations, but its role in HIV-infected population have
      not been studied; in addition, the immune pathways involved are not clear and
      noninvasive immune markers with predictive value are lacking. Our objective was
      to determine the association of select markers of inflammation with PTB in HIV-1
      infected pregnant women. Methods: Within a randomized trial of pregnant women
      receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested
      a case-control study (n = 107; 26 cases, 81 controls) to determine the
      association of maternal inflammation with PTB. Cases were defined as PTB (<37
      weeks' gestational age). We assessed inflammation by measuring plasma levels of
      markers of general inflammation (C-reactive protein [CRP]), intestinal barrier
      dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial
      translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]).
      Multivariable logistic regression was used to determine the odds of PTB per log2
      increase of each marker. Results: In multivariable models, there was increased
      odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95%
      confidence interval [CI], 1.24-4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43
      10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log2 CRP (aOR,
      0.72; 95% CI, .48-1.09). Conclusions: Our results show that select immune markers
      can identify women at higher risk for PTB in HIV-1-infected populations and
      suggest that modulating gut barrier integrity and microbial translocation may
      affect PTB. Clinical Trials Registration: NCT00061321.

PMID- 29590321
TI  - Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of
      Hypertension, Diabetes, and Alzheimer's Disease.
AB  - BACKGROUND: Hypertension affects 33% of Americans while type 2 diabetes and
      Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine
      receptor 3 gene (RYR3) codes for the RYR which functions to release stored
      endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+
      concentration. Increasing studies demonstrate that altered levels of
      intracellular Ca2+ affect cardiac contraction, insulin secretion, and
      neurodegeneration. In this study, we investigated associations of the RYR3
      genetic variants with hypertension, AD, and diabetes. METHODS: Family data sets
      were used to explore association of RYR3 polymorphisms with risk and age at onset
      (AAO) of hypertension, diabetes, and AD. RESULTS: Family-based association tests
      using generalized estimating equations (FBAT-GEE) showed several unique or shared
      disease-1 associated variants in the RYR3 gene. Three single nuclear
      polymorphisms (SNPs; rs2033610, rs2596164, and rs2278317) are significantly
      associated with risk for hypertension, diabetes, and AD. Two SNPs (rs4780174 and
      rs7498093) are significantly associated with AAO of the 3 diseases. CONCLUSIONS:
      RYR3 variants are associated with hypertension, diabetes, and AD. Replication of
      these results of this gene in these 3 complex traits may help to better
      understand the genetic basis of calcium-signaling gene, RYR3 in association with
      risk and AAO of these diseases.

PMID- 29590322
TI  - Clostridium difficile Guidelines.

PMID- 29590323
TI  - Reply to Jacob and Colebunders.

PMID- 29590324
TI  - Universal school lunch programme closes a socioeconomic gap in fruit and
      vegetable intakes among school children in Japan.
AB  - Background: Universal school lunch programmes are expected to cover all children
      equally, compared with selective programmes that may stigmatize socially
      vulnerable children. However, the effectiveness of universal programmes in
      closing dietary disparity has not been empirically proven. We evaluated whether
      Japan's universal school lunch programmes contribute to a reduction in the
      socioeconomic status (SES)-related gradient in fruit and vegetable intakes.
      Methods: We analyzed data for 719 school children aged 6-12 years in a population
      based survey conducted in the greater Tokyo metropolitan area. We measured
      dietary intakes using a validated self-administered brief diet history
      questionnaire for young children (BDHQ-10 y). We assessed parental education,
      annual household income and maternal employment status as SES indicators of
      children. We used multiple regression to estimate mean fruit and vegetable
      intakes by parental education and household income, and the contribution of
      school lunch to reducing the SES-related gradient in fruit and vegetable intakes.
      Results: Compared with children with high maternal education (>15 years), those
      with low maternal education (<13 years) had less vegetable intake by 22.3 g/1000
      kcal (95% confidence interval = 12.5, 32.2) and less fruit intake by 7.5 g/1000
      kcal (95% confidence interval = -2.4, 17.3). However, fruit and vegetable intakes
      from school lunch did not vary by SES, indicating that school lunch intake
      alleviated the SES-related gradient of total vegetable intake by 9.9% and that of
      fruit intake by 3.4%. Conclusions: Universal school lunch programmes can
      partially contribute to a reduction in the SES-related gradient in dietary
      intakes.

PMID- 29590325
TI  - Real-time Monitoring using a breathalyzer-based eHealth system can identify
      lapse/relapse patterns in alcohol use disorder Patients.
AB  - Aim: We introduce a new remote real-time breathalyzer-based method for monitoring
      and early identification of lapse/relapse patterns for alcohol use disorder (AUD)
      patients using a composite measure of sobriety, the Addiction Monitoring Index
      (AMI). Methods: We constructed AMI from (a) obtained test results and (b) the
      pattern of ignored tests using data from the first 30 patients starting in the
      treatment arms of two on-going clinical trials. The patients performed 2-4
      scheduled breath alcohol content (BrAC)-tests per day presented as blood alcohol
      content (BAC) data. In total, 10,973 tests were scheduled, 7743 were performed
      and 3230 were ignored during 3982 patient days. Results: AMI-time profiles could
      be used to monitor the daily trends of alcohol consumption and detect early signs
      of lapse and relapses. The pattern of ignored tests correlates with the onset of
      drinking. AMI correlated with phosphatidyl ethanol (n = 61, F-ratio = 34.6, P <
      0.0001, R = -0.61). The recognition of secret drinking could further be improved
      using a low alcohol detection threshold (BrAC = 0.025 mg/l, BACSwe = 0.050/00 or
      US = 0.0053g/dl), in addition to the legal Swedish traffic limit (BrAC = 0.1
      mg/l, BACSwe = 0.20/00 or US = 0.021 g/dl). Nine out of 10 patients who dropped
      out from the study showed early risk signs as reflected in the level and pattern
      in AMI before the actual dropout. Conclusions: AMI-time profiles from an eHealth
      system are useful for monitoring the recovery process and for early
      identification of lapse/relapse patterns. High-resolution monitoring of sobriety
      enables new measurement-based treatment methods for proactive personalized long
      term relapse prevention and treatment of AUD patients. Clinical Trial
      Registration: The data used for construction of AMI was from two clinical trials
      approved by the Regional Ethics Committee of Uppsala, Sweden and performed in
      accordance with the Declaration of Helsinki. Written informed consent was
      obtained from all participating subjects. The study was registered at
      ClinicalTrials.gov (NCT03195894).

PMID- 29590327
TI  - Is Scottish Intercollegiate Guidelines Network guidance for GP management of
      tonsillitis suitable? A qualitative study.
AB  - Background: The Scottish Intercollegiate Guidelines Network (SIGN) developed
      guidelines for the management of sore throat and indications for tonsillectomy in
      1999 to address concerns of unnecessary surgery. Emergency admissions to hospital
      for tonsillitis have since increased. Adults experience an average of 27 episodes
      of tonsillitis before undergoing tonsillectomy. We wished to explore the
      appropriateness of the guidance and/or its implementation in primary care. Aim:
      To explore the attitudes of GPs to the referral criteria they use when managing
      adults presenting with acute tonsillitis. Design: Secondary analysis of
      qualitative data from the NAtional Trial of Tonsillectomy IN Adults (NATTINA)
      feasibility and process evaluation. Participants and Setting: Twenty-one GPs from
      practices throughout the UK. Method: In-depth interviews with GPs concerning both
      the feasibility and process evaluation phases of NATTINA. Analysis was conducted
      using the framework method. Results: GPs felt it was rarely necessary to refer
      patients. They were aware of guidelines and would refer if requested by a patient
      who fulfilled the guidelines criteria and/or who were missing considerable
      amounts of work. Conclusion: The introduction of the guidelines appears to
      coincide with what some may have hoped to be a desired effect of reducing adult
      sore throat referrals and subsequent tonsillectomies by increasing the number of
      episodes a patient must suffer before the referral threshold is met. GPs may find
      equipoise for tonsillectomy referral challenging as many patients express a
      strong preference for surgery. We believe this paper reinforces GP
      professionalism and patient-centred consultations, and challenges the role of
      clinical guidelines.

PMID- 29590326
TI  - Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus
      Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on
      Antiretroviral Therapy.
AB  - Background: Herpes zoster (HZ) risk is increased in human immunodeficiency virus
      (HIV)-infected persons. Live attenuated zoster vaccine (ZV) reduces HZ incidence
      and severity in adults; safety and immunogenicity data in HIV-infected adults are
      limited. Methods: We conducted a randomized, double-blind, placebo-controlled
      trial in HIV-infected adults virally suppressed on antiretroviral therapy (ART).
      Participants, stratified by CD4+ count (200-349 or >=350 cells/uL), were
      randomized 3:1 to receive ZV or placebo on day 0 and week 6. The primary endpoint
      was serious adverse event or grade 3/4 signs/symptoms within 6 weeks after each
      dose. Immunogenicity (varicella zoster virus [VZV]-specific glycoprotein enzyme
      linked immunosorbent assay and interferon-gamma enzyme-linked immunospot assay
      responses) was assessed at 6 and 12 weeks postvaccination. Results: Of 395
      participants (296 ZV vs 99 placebo), 84% were male, 47% white, 29% black, and 22%
      Hispanic; median age was 49 years. Safety endpoints occurred in 15 ZV and 2
      placebo recipients (5.1% [95% confidence interval {CI}, 2.9%-8.2%] vs 2.1% [95%
      CI, .3%-7.3%]; P = .26). Injection site reactions occurred in 42% of ZV (95% CI,
      36.3%-47.9%) vs 12.4% of placebo recipients (95% CI, 6.6%-20.6%) (P < .001). Week
      12 median natural log VZV antibody titer was higher for ZV (6.30 [Q1, Q3, 5.64,
      6.96]) vs placebo (5.48 [Q1, Q3, 4.63, 6.44]; P < .001) overall and in the high
      CD4+ stratum (P = .003). VZV antibody titers were similar after 1 or 2 ZV doses.
      Polymerase chain reaction-confirmed HZ occurred in 2 participants (1 ZV; 1
      placebo); none was vaccine strain related. Conclusions: Two doses of ZV in HIV
      infected adults suppressed on ART with CD4+ counts >=200 cells/uL were safe and
      immunogenic. Clinical Trials Registration: NCT00851786.

PMID- 29590328
TI  - Association between adolescents' academic aspirations and expectations and mental
      health: a one-year follow-up study.
AB  - Background: Mental health problems among youth have increased in Sweden in recent
      decades, as has competition in higher education and the labour market. It is
      unknown whether the increasing emphasis put on educational achievement might
      negatively affect adolescents' mental health. We aimed to investigate the
      relationship between adolescents' academic aspirations and expectations and the
      risk of mental health problems. Methods: We studied 3343 Swedish 7th grade
      adolescents (age 13), who participated in the first two waves of the KUPOL
      longitudinal study; participants answered a questionnaire encompassing the five
      item Future Aspirations and Goals (FG) subscale of the Student Engagement
      Instrument, two questions about their own academic aspirations and expectations
      and two mental health instruments: the Center for Epidemiological studies for
      Children (CES-DC) (alpha=.90) and the Strengths and Difficulties Questionnaire
      (SDQ) (alpha=.78). The association between aspirations and expectations at
      baseline and mental health at follow-up was analysed using logistic regression
      models adjusting for baseline mental health, socio-demographic and family
      factors. Results: The FG subscale was inversely and linearly associated with the
      odds of high CES-DC score [adjusted OR (odds ratio) 0.71, 95% CI (confidence
      interval): 0.59-0.86], total Strengths and Difficulties Questionnaire score (OR
      0.59, 95% CI 0.49-0.71), and its internalizing (OR 0.70, 95% CI 0.59-0.84) and
      externalizing problems scores (OR 0.58, 95% CI 0.48-0.71). Conclusions:
      Adolescents with high individual academic aspirations have less mental health
      problems at 1-year follow-up. Future studies should investigate whether
      interventions aimed at increasing aspirations and engagement in school may
      prevent mental health problems in adolescence.

PMID- 29590329
TI  - Association of Author Gender With Sex Bias in Surgical Research.
AB  - Importance: Previous studies demonstrate sex bias in surgical research. Female
      participants and investigators are underrepresented in surgical scientific
      research. Objectives: To describe the distribution of male and female authors in
      5 general-interest surgery journals, assess the association of author gender with
      sex bias, and explore whether investigators benefit from performing sex-inclusion
      research. Design, Setting, and Participants: For this bibliometric analysis, data
      were abstracted from 1921 original, peer-reviewed articles published from January
      1, 2011, through December 31, 2012, in Annals of Surgery, American Journal of
      Surgery, JAMA Surgery, The Journal of Surgical Research, and Surgery. Excluded
      articles pertained to a sex-specific disease or did not report the number of
      study participants. An additional 119 articles contained gender-ambiguous author
      names and were omitted. Data were analyzed from April to June 2017. Main Outcomes
      and Measures: Male and female first and senior authors, number of female and male
      participants in each study, surgical specialty, and number of citations received
      per article. Results: Of the 3604 authors of 1802 articles included in this
      study, 2791 first and senior authors (77.4%) were male and 813 (22.6%) were
      female. The prevalence of male and female authors was consistent across all 5
      journals and among clinical and basic science research. Articles by female
      authors included a higher median number of female study participants compared
      with their male counterparts (27.5 vs 16.0; P = .01), but sex matched the
      inclusion of participants less frequently (36% vs 45%; P = .001). No sex-based
      differences occurred between male and female authors in reporting, statistical
      analysis, and discussion of the data or in the number of citations received.
      Compared with studies that did not report, analyze, or discuss data by sex,
      studies that performed sex-specific data reporting yielded a mean of 2.8 more
      citations (95% CI, 1.2-4.4; P = .001); those that performed statistical analysis,
      a mean of 3.5 more citations (95% CI, 1.8-5.1; P = .001); and those that
      discussed the data, a mean of 2.6 more citations (95% CI, 0.7-4.5; P = .001).
      Articles with a higher percentage of sex matching of participants also received
      more citations, with an increase of 1 citation per 4.8% (95% CI, 2.0%-7.7%; P =
      .001) increase in percentage of sex matching. Conclusions and Relevance: Sex bias
      in surgical research is prevalent among male and female authors; however, female
      authors included proportionally more female participants in their studies
      compared with male authors. Notably, studies that addressed sex bias were
      rewarded by the scientific community with increased citations of their published
      work.

PMID- 29590330
TI  - Arterial stiffening is a heritable trait associated with arterial dilation but
      not wall thickening: a longitudinal study in the twins UK cohort.
AB  - Aims: Vascular ageing is characterized by arterial stiffening, dilation, and
      arterial wall thickening. We investigated the extent to which these changes are
      related and their heritability during 5 year follow-up in the Twins UK cohort.
      Methods and results: Carotid-femoral pulse wave velocity (PWVcf), carotid
      diameter, carotid distensibility, and carotid intima-media thickness (IMT) were
      measured in 762 female twins (mean age 57.9 +/- 8.6 years) at two time-points
      over an average follow-up of 4.9 +/- 1.5 years. Magnetic resonance imaging (MRI)
      was performed in a sub-sample of 38 women to measure aortic pulse wave velocity
      (PWVaorta), diameter, and wall thickness. Heritability of changes in arterial
      wall properties was estimated using structural equation modelling. Annual
      increases in PWVcf, carotid diameter, distensibility, and IMT were 0.139 m/s,
      0.028 mm, -0.4 kPa-1, and 0.011 mm per year, respectively. In regression
      analysis, predictors of progression in PWVcf included age, mean arterial pressure
      (MAP), and heart rate (HR) at baseline, and progression in MAP, HR, and body mass
      index (BMI). Predictors of progression in IMT included progression in MAP, BMI,
      and triglyceride levels. Progression of PWV and distensibility correlated with
      progression in carotid diameter but not with IMT. Heritability of progression of
      PWVcf, diameter, and IMT was 55%, 21%, and 8%, respectively. In a sub-sample of
      women that underwent MRI, aortic wall thickness increased by 0.19 mm/year, but
      aortic wall thickening was not correlated with an increase in lumen diameter or
      PWVaorta. Conclusion: Arterial stiffening, as measured by PWVcf, and dilation are
      heritable but independent of arterial wall thickening. Genetic and cardiovascular
      risk factors contribute differently to progression of PWV and IMT.

PMID- 29590331
TI  - Heat Strain and Hydration of Japanese Construction Workers during Work in Summer.
AB  - Objectives: The aim was to ascertain hydration and heat strain of construction
      workers in Japan during the summer who are at the highest risk of heat-related
      disorders. Methods: The subjects were 23 construction workers, whose average age
      was 41, average weight was 69 kg, and average height was 170 cm. We measured
      thermal working conditions with a wet bulb globe temperature (WBGT) measurement
      instrument affixed to the helmet of each worker, at fixed points outdoors in the
      sun and indoors. Heat strain was evaluated for water intake, urine specific
      gravity (Usg), urine temperature (UT), heart rate (HR), and body weight during
      work. Results: The average WBGT measured on the worker helmets over 3 consecutive
      days was 28.0 +/- 0.7, 27.6 +/- 0.8, and 27.6 +/- 1.1 degrees C. The average
      water intake was 2.6 l during a work shift. The average Usg, UT, and % HR reserve
      were the highest in the first half of afternoon work. Seventy-eight percent of
      the subjects exceeded at least one of the ACGIH TLV physiological guidelines for
      heat strain in terms of HR and weight loss or a clinically dehydrated level of
      Usg. Conclusions: Heat strain was the highest in the first half of afternoon
      work. The number of dehydrated workers increased during this shift because of
      insufficient water intake. Adequate hydration is required to decrease the risk of
      heat-related disorders among construction workers in the summer.

PMID- 29590332
TI  - Subclinical coronary artery disease in Swiss HIV-positive and HIV-negative
      persons.
AB  - Aims: HIV-positive persons have increased cardiovascular event rates but data on
      the prevalence of subclinical atherosclerosis compared with HIV-negative persons
      are not uniform. We assessed subclinical atherosclerosis utilizing coronary
      artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA)
      in 428 HIV-positive participants of the Swiss HIV Cohort Study and 276 HIV
      negative controls concurrently referred for clinically indicated CCTA. Methods
      and results: We assessed the association of HIV infection, cardiovascular risk
      profile, and HIV-related factors with subclinical atherosclerosis in univariable
      and multivariable analyses. HIV-positive participants (median duration of HIV
      infection, 15 years) were younger than HIV-negative participants (median age 52
      vs. 56 years; P < 0.01) but had similar median 10-year Framingham risk scores
      (9.0% vs. 9.7%; P = 0.40). The prevalence of CAC score >0 (53% vs. 56.2%; P =
      0.42) and median CAC scores (47 vs. 47; P = 0.80) were similar, as was the
      prevalence of any, non-calcified/mixed, and high-risk plaque. In multivariable
      adjusted analysis, HIV-positive participants had a lower prevalence of calcified
      plaque than HIV-negative participants [36.9% vs. 48.6%, P < 0.01; adjusted odds
      ratio (aOR) 0.57; 95% confidence interval (CI) 0.40-0.82; P < 0.01], lower
      coronary segment severity score (aOR 0.72; 95% CI 0.53-0.99; P = 0.04), and lower
      segment involvement score (aOR 0.71, 95% CI 0.52-0.97; P = 0.03). Advanced
      immunosuppression was associated with non-calcified/mixed plaque (aOR 1.97; 95%
      CI 1.09-3.56; P = 0.02). Conclusion: HIV-positive persons in Switzerland had a
      similar degree of non-calcified/mixed plaque and high-risk plaque, and may have
      less calcified coronary plaque, and lower coronary atherosclerosis involvement
      and severity scores than HIV-negative persons with similar Framingham risk
      scores.

PMID- 29590333
TI  - Patent foramen ovale closure vs. medical therapy for cryptogenic stroke: a meta
      analysis of randomized controlled trials.
AB  - Aims: The efficacy of patent foramen ovale (PFO) closure for cryptogenic stroke
      has been controversial. We undertook a meta-analysis of randomized controlled
      trials (RCTs) comparing device closure with medical therapy to prevent recurrent
      stroke for patients with PFO. Methods and results: We systematically identified
      all RCTs comparing device closure to medical therapy for cryptogenic stroke in
      patients with PFO. The primary efficacy endpoint was recurrent stroke, analysed
      on an intention-to-treat basis. The primary safety endpoint was new onset atrial
      fibrillation (AF). Five studies (3440 patients) were included. In all, 1829
      patients were randomized to device closure and 1611 to medical therapy. Across
      all patients, PFO closure was superior to medical therapy for prevention of
      stroke [hazard ratio (HR) 0.32, 95% confidence interval (95% CI) 0.13-0.82; P =
      0.018, I2 = 73.4%]. The risk of AF was significantly increased with device
      closure [risk ratio (RR) 4.68, 95% CI 2.19-10.00, P<0.001, heterogeneity I2 =
      27.5%)]. In patients with large shunts, PFO closure was associated with a
      significant reduction in stroke (HR 0.33, 95% CI 0.16-0.72; P = 0.005), whilst
      there was no significant reduction in stroke in patients with a small shunt (HR
      0.90, 95% CI 0.50-1.60; P = 0.712). There was no effect from the presence or
      absence of an atrial septal aneurysm on outcomes (P = 0.994). Conclusion: In
      selected patients with cryptogenic stroke, PFO closure is superior to medical
      therapy for the prevention of further stroke: this is particularly true for
      patients with moderate-to-large shunts. Guidelines should be updated to reflect
      this.

PMID- 29590336
TI  - Importance of Objectively Comparing Local VA and Non-VA Care and Outcomes:
      Serving Veterans Well.

PMID- 29590334
TI  - A rare missense mutation in MYH6 associates with non-syndromic coarctation of the
      aorta.
AB  - Aims: Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart
      defects (CHDs) and confers substantial morbidity despite treatment. It is
      increasingly recognized as a highly heritable condition. The aim of the study was
      to search for sequence variants that affect the risk of CoA. Methods and results:
      We performed a genome-wide association study of CoA among Icelanders (120 cases
      and 355 166 controls) based on imputed variants identified through whole-genome
      sequencing. We found association with a rare (frequency = 0.34%) missense
      mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 * 10-22), encoding the
      alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein.
      Approximately 20% of individuals with CoA in Iceland carry this mutation. We show
      that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic
      valve. We have previously reported broad effects of p.Arg721Trp on cardiac
      electrical function and strong association with sick sinus syndrome and atrial
      fibrillation. Conclusion: Through a population approach, we found that a rare
      missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on
      the risk of CoA and explains a substantial fraction of the Icelanders with CoA.
      This is the first mutation associated with non-familial or sporadic form of CoA
      at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with
      highly variable expressivity and emphasizes the importance of sarcomere integrity
      for cardiac development and function.

PMID- 29590335
TI  - First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human
      Immunodeficiency Virus Type 2 (HIV-2) Infection: A Phase 2, Noncomparative Trial
      (ANRS 159 HIV-2).
AB  - Background: New options for first-line treatment of human immunodeficiency virus
      type 2 (HIV-2) infection are needed. We evaluated an integrase inhibitor
      (raltegravir)-containing regimen. Methods: Antiretroviral therapy (ART)-naive
      adults with symptomatic infection by HIV-2 only, CD4 count <500 cells/MUL or CD4
      decrease >50 cells/MUL/year over the past 3 years, or a confirmed plasma HIV-2
      RNA (pVL) load >=100 copies/mL were eligible for this noncomparative trial. The
      composite primary endpoint was survival at 48 weeks without any of the following:
      CD4 gain from baseline <100 cells/MUL, confirmed pVL >=40 copies/mL from week 24,
      raltegravir permanent discontinuation, or incident B or C event. HIV-2
      ultrasensitive pVL (uspVL) and total DNA were assessed using in-house polymerase
      chain reaction (PCR) assays. Results: Baseline median CD4 count of 30 enrolled
      individuals (67% women) was 436 cells/uL (interquartile range [IQR], 314-507
      cells/uL); pVL was >=40 copies/mL in 67% of them, uspVL was >=5 copies/mL in 92%,
      and total DNA was >6 copies by PCR in 32%. At week 48, the composite endpoint of
      success was reached in 40% [95% confidence interval, 22.7%-59.4%]. Failure was
      mainly (50%) due to CD4 gain <100 cells/uL; uspVL was <5 copies/mL in 87% and
      total DNA >6 copies by PCR in 12% of participants. Median CD4 gain was 87
      cells/uL (IQR, 38-213 cells/uL; n = 28). No serious adverse reactions were
      reported. Conclusions: Raltegravir-containing ART is a safe option for first-line
      treatment of HIV-2 infection, yielding a comparable success rate to protease
      inhibitors. Clinical Trials Registration: NCT 01605890.

PMID- 29590337
TI  - Associations between physical fitness and adherence to the Mediterranean diet
      with health-related quality of life in adolescents: results from the LabMed
      Physical Activity Study.
AB  - Background: Physical fitness (PF) and adherence to the Mediterranean diet are
      important indicators of healthy lifestyles. The purpose of this study is to
      analyze the independent and combined associations between PF and adherence to
      Mediterranean diet with health-related quality of life (HRQoL) in adolescents.
      Methods: This is a cross-sectional analysis with 956 Portuguese adolescents aged
      12-18 years. HRQoL was measured with the Kidscreen-10 questionnaire. PF was
      assessed with the ALPHA health-related fitness battery. The 20-m shuttle run test
      was used for the estimation of cardiorespiratory fitness; handgrip strength and
      standing long jump tests were applied for the assessment of muscular fitness and
      the 4 * 10 m shuttle run test for the assessment of motor fitness (speed and
      agility). The results of the PF tests (cardiorespiratory fitness, muscular
      fitness and motor fitness) were transformed into standardized values (Z-scores)
      by age and sex. Adherence to the Mediterranean diet was assessed with the KIDMED
      index. Regression analysis and analysis of covariance were performed. Results: PF
      (B = 0.228; P < 0.05) and adherence to the Mediterranean diet (B = 0.259; P <
      0.05) were positively associated with HRQoL, after controlling for several
      variables. Participants classified as high PF and high adherence to Mediterranean
      diet had on average the highest HRQoL score compared with those with low PF and
      low adherence to Mediterranean diet (F(3, 939) = 4.270; P = 0.005), after
      adjustments for potential confounders. Conclusions: The combination of high PF
      levels and optimal adherence to Mediterranean diet is positively associated with
      HRQoL.

PMID- 29590338
TI  - An intervention that reduces stress in people who combine work with informal
      care: randomized controlled trial results.
AB  - Background: The aim of the research was to examine whether a role-focused self
      help course intervention would decrease caregiver stress and distress, and
      functioning problems, among people who suffer stress because they combine paid
      work with informal care. Methods: A pre-registered (NTR 5528) randomized
      controlled design was applied (intervention vs. wait list control). Participants
      (n = 128) were people who had paid work and were suffering stress due to their
      involvement in informal care activities. Participants allocated to the
      intervention group (n = 65) received the role-focused self-help course. Control
      group members (n = 63) received this intervention after all measurements. Prior
      to the random allocation (pre-test), and 1 month (post-test 1) and 2 months (post
      test 2) after allocation, all participants completed a questionnaire that
      measured their caregiver stress (primary outcome), distress, work functioning,
      negative care-to-work interference and negative care-to-social and personal life
      interference. Mixed model ANOVAs were used to test the effectiveness of the
      intervention. Results: Two months after allocation, the intervention group
      participants had lower levels of caregiver stress and distress compared with the
      control group participants. The intervention did not directly resolve impaired
      work functioning or interference of care with work and social/personal life.
      Conclusion: The intervention decreases caregiver stress and distress in people
      who suffer stress because they combine paid work with informal caring. The
      intervention (Dutch version) can be downloaded at no cost from
      www.amc.nl/mantelzorgstress.

PMID- 29590339
TI  - POPdemog: visualizing population demographic history from simulation scripts.
AB  - Summary: We present POPdemog, an R package which converts coalescent simulation
      program input parameters into a visual representation of the demographic model.
      This package is useful for preparing figures, for checking that demographic
      simulation parameters have been correctly specified, and for understanding
      demographic models that other researchers have used to simulate genetic data. The
      POPdemog package supports the ms, msa, msHot, MaCS, msprime, scrm and Cosi2
      programs, and includes options for customizing the output figures. Availability
      and implementation: The POPdemog package and its tutorial can be freely
      downloaded from https://github.com/YingZhou001/POPdemog. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29590340
TI  - Exercise cardiac magnetic resonance to differentiate athlete's heart from
      structural heart disease.
AB  - Aims: The distinction between left ventricular (LV) dilation with mildly reduced
      LV ejection fraction (EF) in response to regular endurance exercise training and
      an early cardiomyopathy is a frequently encountered and difficult clinical
      conundrum. We hypothesized that exercise rather than resting measures would
      provide better discrimination between physiological and pathological LV
      remodelling and that preserved exercise capacity does not exclude significant LV
      damage. Methods and results: We prospectively included 19 subjects with LVEF
      between 40 and 52%, comprising 10 ostensibly healthy endurance athletes (EA
      healthy) and nine patients with dilated cardiomyopathy (DCM). In addition, we
      recruited five EAs with a region of subepicardial LV. Receiver operating
      characteristic fibrosis (EA-fibrosis). Cardiac magnetic resonance (CMR) imaging
      was performed at rest and during supine bicycle exercise. Invasive afterload
      measures were obtained to enable calculations of biventricular function relative
      to load (an estimate of contractility). In DCM and EA-fibrosis subjects there was
      diminished augmentation of LVEF (5 +/- 6% vs. 4 +/- 3% vs. 14 +/- 3%; P = 0.001)
      and contractility [LV end-systolic pressure-volume ratio, LVESPVR; 1.4 (1.3-1.6)
      vs. 1.5 (1.3-1.6) vs. 1.8 (1.7-2.7); P < 0.001] during exercise relative to EA
      healthy. Receiver-operator characteristic curves demonstrated that a cut-off
      value of 11.2% for DeltaLVEF differentiated DCM and EA-fibrosis patients from EA
      healthy [area under the curve (AUC) = 0.92, P < 0.001], whereas resting LVEF and
      VO2max were not predictive. The AUC value for LVESPVR ratio was similar to that
      of DeltaLVEF. Conclusions: Functional cardiac evaluation during exercise is a
      promising tool in differentiating healthy athletes with borderline LVEF from
      those with an underlying cardiomyopathy. Excellent exercise capacity does not
      exclude significant LV damage.

PMID- 29590341
TI  - Association between vaccination coverage decline and influenza incidence rise
      among Italian elderly.
AB  - After a peak of 68.3% during the 2005-06 season, influenza vaccine coverage among
      Italian elderly showed an unprecedented, prolonged decline. According to the
      National surveillance network, the vaccination coverage was <=50% during two of
      the last three seasons (2014-17). In parallel, influenza-like illness (ILI) rates
      increased from 2.71% in the triennium 2005-08, to 4.24% in the last triennium. A
      significant association was found between ILI rise and vaccine coverage decline
      (P = 0.036), and according to a conservative estimation, each 1% increase in
      coverage may prevent >=2690 ILI cases among the elderly. A reinforcement of
      influenza immunization policies is strongly needed in Italy.

PMID- 29590343
TI  - Expanding the Use of Primaquine for the Radical Cure of Plasmodium vivax.

PMID- 29590344
TI  - Ethno-cultural origins, health beliefs and mothers' behavior regarding infant
      vaccinations in Israel.
AB  - To compare the health beliefs and infant vaccination behavior of mothers of four
      different ethno-cultural backgrounds: Israeli-born Jewish and Arab-Bedouin and
      immigrants from the Former Soviet Union and Ethiopia; to examine the associations
      between initial and subsequent infant vaccination behaviors of mothers and to
      identify predictors of vaccination behaviors. A comparative cross-sectional study
      was conducted in selected community neighborhoods. A quota sample included 100
      mothers with infants aged 18-24 months (N = 400) from each of the four ethno
      cultural groups. Data were collected through questionnaires and examination of
      the infant vaccination cards. Both groups of immigrant mothers had the lowest
      adherence to the recommended vaccination regime. Our findings indicate that
      maternal behaviors regarding infant vaccinations were determined mainly by the
      behavior at the previous recommended vaccination stage. Different ethno-cultural
      groups presented different sociodemographic predictors of vaccination behaviors.
      These predictors only affected the vaccinations at the early stage of 2 months.
      Policy makers should be aware that mother's vaccination behaviors vary according
      to ethno-cultural groups to establish culturally tailored intervention programs.

PMID- 29590342
TI  - Protein synthesis levels are increased in a subset of individuals with fragile X
      syndrome.
AB  - Fragile X syndrome (FXS) is a monogenic form of intellectual disability and
      autism spectrum disorder caused by the absence of the fragile X mental
      retardation protein (FMRP). In biological models for the disease, this leads to
      upregulated mRNA translation and as a consequence, deficits in synaptic
      architecture and plasticity. Preclinical studies revealed that pharmacological
      interventions restore those deficits, which are thought to mediate the FXS
      cognitive and behavioral symptoms. Here, we characterized the de novo rate of
      protein synthesis in patients with FXS and their relationship with clinical
      severity. We measured the rate of protein synthesis in fibroblasts derived from
      32 individuals with FXS and from 17 controls as well as in fibroblasts and
      primary neurons of 27 Fmr1 KO mice and 20 controls. Here, we show that levels of
      protein synthesis are increased in fibroblasts of individuals with FXS and Fmr1
      KO mice. However, this cellular phenotype displays a broad distribution and a
      proportion of fragile X individuals and Fmr1 KO mice do not show increased levels
      of protein synthesis, having measures in the normal range. Because the same Fmr1
      KO animal measures in fibroblasts predict those in neurons we suggest the
      validity of this peripheral biomarker. Our study offers a potential explanation
      for the comprehensive drug development program undertaken thus far yielding
      negative results and suggests that a significant proportion, but not all
      individuals with FXS, may benefit from the reduction of excessive levels of
      protein synthesis.

PMID- 29590345
TI  - Proactive Infliximab Monitoring Following Reactive Testing is Associated With
      Better Clinical Outcomes Than Reactive Testing Alone in Patients With
      Inflammatory Bowel Disease.
AB  - Background and Aims: Reactive testing has emerged as the new standard of care for
      managing loss of response to infliximab in inflammatory bowel disease [IBD].
      Recent data suggest that proactive infliximab monitoring is associated with
      better therapeutic outcomes in IBD. Nevertheless, there are no data regarding the
      clinical utility of proactive infliximab monitoring after first reactive testing.
      We aimed to evaluate long-term outcomes of proactive infliximab monitoring
      following reactive testing compared with reactive testing alone in patients with
      IBD. Methods: This was a retrospective multicenter cohort study of consecutive
      IBD patients on infliximab maintenance therapy receiving a first reactive testing
      between September 2006 and January 2015. Patients were divided into two groups;
      Group A [proactive infliximab monitoring after reactive testing] and Group B
      [reactive testing alone]. Patients were followed through December 2015. Time-to
      event analysis for treatment failure and IBD-related surgery and hospitalization
      was performed. Treatment failure was defined as drug discontinuation due to
      either loss of response or serious adverse event. Results: The study population
      consisted of 102 [n = 70, 69% with CD] patients [Group A, n = 33 and Group B, n =
      69] who were followed for (median, interquartile range [IQR]) 2.7 [1.4-3.8]
      years. Multiple Cox regression analysis identified proactive following reactive
      TDM as independently associated with less treatment failure (hazard ratio [HR]
      0.15; 95% confidence interval [CI] 0.05-0.51; p = 0.002) and fewer IBD-related
      hospitalizations [HR: 0.18; 95% CI 0.05-0.99; p = 0.007]. Conclusions: This study
      showed that proactive infliximab monitoring following reactive testing was
      associated with greater drug persistence and fewer IBD-related hospitalizations
      than reactive testing alone.

PMID- 29590346
TI  - Data resource profile: The Canadian Hospitalization and Taxation Database (C
      HAT).

PMID- 29590347
TI  - Association of Vitamin D deficiency with peripheral arterial disease: a meta
      analysis of literature studies.
AB  - Context: Vitamin D deficiency patients have an increased cardiovascular (CV)
      morbidity and mortality. Contrasting data are available about the association
      between peripheral arterial disease (PAD) and Vitamin D status. Objective: To
      perform a meta-analysis of studies evaluating the association between Vitamin D
      status and PAD. Data sources: Studies were systematically searched in the PubMed,
      Web of Science, Scopus and EMBASE databases. Results: Ten studies with data on
      Vitamin D levels in 2,079 PAD patients and 18,233 non-PAD controls and 6 studies
      on the prevalence of PAD in 23,171 subjects with Vitamin D deficiency (<20
      ng/ml), 48,311 subjects with Vitamin D insufficiency (20-30 ng/ml) and 27,910
      with normal Vitamin D levels (>30 ng/ml) were included. Compared to controls, PAD
      patients showed significantly lower Vitamin D levels (MD: -2.24 ng/ml; 95%CI: 
      3.38, -1.10; p<0.001, I2=86.5%; p<0.001). Moreover, a higher prevalence of PAD
      was found both in subjects with Vitamin D insufficiency (OR: 1.098, 95%CI: 1.010
      1.195, p=0.029, I2: 0%, p=0,600) and in subjects with Vitamin D deficiency (OR:
      1.484, 95%CI: 1.348-1.635, p<0.001, I2: 7.65%, p=0,367) compared with controls
      with normal Vitamin D levels. Sensitivity analyses and the analysis of data on
      the cumulative risk of PAD according to Vitamin D levels derived from
      multivariate analysis consistently confirmed results. Conclusions: PAD patients
      have lower vitamin D levels than controls and both Vitamin D deficiency and
      Vitamin D insufficiency are significantly associated with PAD. Reduced Vitamin D
      levels might represent an independent risk factor for PAD and, in turn, for CV
      events.

PMID- 29590348
TI  - Improving quality care for diabetes in the community: What do Cypriot patients
      want?
AB  - Objective: To measure patient preferences for their diabetic care in community
      setting. Design: Discrete-choice survey. Setting: Community setting (primary
      physician and hospital sites) in Cyprus. Participants: Diabetic patients
      attending community sites. Main Outcome Measure(s): Patient preferences, to
      estimate which components of quality healthcare service people value, their
      relative importance but also the potential shift to shared decision-making (SDM).
      Results: Older respondents with experience of the private sector already received
      SDM (managing their care and choosing their treatments; detailed and accurate
      information, continuity of care; compassion for their personal situation) from
      their primary care physician with waiting time shorter than 1 h. They valued
      their 'current' option and they did not want to change it with other services.
      Younger people from the public sector valued a change in policy and wanted to
      move from their 'current' to alternative diabetic care services where the waiting
      times were shorter, they could not only manage their care but also choose their
      treatments (together with receiving information, continuity of care and
      compassionate care). Individuals agreed with receiving multidisciplinary care
      from a team of healthcare providers but they mostly preferred being supported by
      their primary care physician. The pooled sample valued their 'current' option but
      they also supported policy changes that would implement SDM service for
      everybody. Conclusions: Diabetic patients value SDM and are willing to support a
      shift of practice to receive it not only in the private but also in the public
      sector. The forthcoming National Health Insurance Service would aim to address
      such developments as anticipated both in the European Troika's recommendations
      and the relevant laws.

PMID- 29590349
TI  - UK consumer perceptions of a novel till-receipt 'traffic-light' nutrition system.
AB  - Front-of-pack (FoP) traffic light nutrition labelling has been widely proposed as
      a tool to improve public health nutrition. Current evidence suggests that whilst
      consumers generally find them to be useful and an important source of information
      about a particular food or ingredient, this may have limited value in isolation
      when considering a person's overall nutritional intake. This study sought to
      examine UK consumers' use of existing FoP traffic light food labelling and
      ascertain public perception of a novel 'till-receipt' summary providing
      nutritional information about consumers entire shopping purchases. In total, 237
      respondents completed an online questionnaire between May and June 2016. Almost
      two-thirds were female (n = 152, 64.1%) and the largest proportion of responses
      were received from those aged 25-32 years (n = 53, 22.4%) and 41-50 years (n =
      53, 22.4%). About 83.5% of respondents suggested that they currently use traffic
      light information to inform their food purchases and 'health' was reported as the
      most important factor influencing food choice (42.2%; n = 100). Notably, 54.4% of
      respondents indicated that the novel till-receipt system could provide a solution
      to the potential limitations of existing FoP labelling and could help inform
      healthier food purchases. Our findings strengthen the existing evidence base to
      suggest that traffic light information is a useful tool to aid consumer food
      purchases. Moreover, our outcomes propose that consumers may benefit from a new
      receipt-based traffic light system which provides a more holistic summary of
      their entire food purchases.

PMID- 29590350
TI  - Usage and accuracy of medication data from nationwide health information exchange
      in Quebec, Canada.
AB  - Objective: (1) To describe the usage of medication data from the Health
      Information Exchange (HIE) at the health care system level in the province of
      Quebec; (2) To assess the accuracy of the medication list obtained from the HIE.
      Methods: A descriptive study was conducted utilizing usage data obtained from the
      Ministry of Health at the individual provider level from January 1 to December
      31, 2015. Usage patterns by role, type of site, and tool used to access the HIE
      were investigated. The list of medications of 111 high risk patients arriving at
      the emergency department of an academic healthcare center was obtained from the
      HIE and compared with the list obtained through the medication reconciliation
      process. Results: There were 31 022 distinct users accessing the HIE 11 085 653
      times in 2015. The vast majority of pharmacists and general practitioners
      accessed it, compared to a minority of specialists and nurses. The top 1% of
      users was responsible of 19% of access. Also, 63% of the access was made using
      the Viewer application, while using a certified electronic medical record
      application seemed to facilitate usage. Among 111 patients, 71 (64%) had at least
      one discrepancy between the medication list obtained from the HIE and the
      reference list. Conclusions: Early adopters were mostly in primary care settings,
      and were accessing it more frequently when using a certified electronic medical
      record. Further work is needed to investigate how to resolve accuracy issues with
      the medication list and how certain tools provide different features.

PMID- 29590351
TI  - Laboratory and Field Evaluation of the Entomopathogenic Fungus Beauveria bassiana
      (Deuteromycotina: Hyphomycetes) for Population Management of Spruce Beetle,
      Dendroctonus rufipennis (Coleoptera: Scolytinae), in Felled Trees and Factors
      Limiting Pathogen Success.
AB  - An isolate of the entomopathogenic fungus Beauveria bassiana (Bals.) Vuill.
      (Deuteromycotina: Hyphomycetes) was tested for its ability to reduce survival and
      reproduction of spruce beetle, Dendroctonus rufipennis (Kirby) (Coleoptera:
      Scolytinae), under laboratory and field conditions. Conidial suspension applied
      directly to adults or to filter papers that adults contacted had a median
      survival time of 3-4 d in laboratory assays and beetles died more rapidly when
      exposed to conidial suspension than when treated with surfactant solution only.
      In the field, conidial suspension was applied to the surface of felled and
      pheromone-baited Engelmann spruce (Picea engelmannii) trees using a backpack
      sprayer. Mortality of colonizing parent beetles (F0), reproduction (abundance of
      F1 offspring in logs), and emergence of F1 beetles from logs was compared between
      treated and nontreated logs. Application of spore suspension increased mortality
      of F0 adults by 36% on average. Total F1 reproduction was reduced by 17% and
      emergence from logs was reduced by 13% in treated logs, but considerable
      variability in reproduction and emergence was observed. Viable spores were re
      isolated from treated logs up to 90 d after application, indicating that spores
      are capable of long-term persistence on the tree bole microhabitat. Subsequent in
      vitro tests revealed that temperatures below 15 degrees C and exposure to spruce
      monoterpenes likely limit performance of B. bassiana under field conditions, but
      exposure to low-intensity light or interactions with spruce beetle symbiotic
      fungi were not strongly inhibitory. It is concluded that matching environmental
      tolerances of biocontrol fungi to field conditions can likely improve their
      usefulness for control of spruce beetle in windthrown trees.

PMID- 29590352
TI  - Developing a community-based intervention for Dutch older adults in a
      socioeconomically disadvantaged community.
AB  - Unhealthy eating and low levels of physical activity are major health risks,
      especially for older adults and people with a low socioeconomic status. The aim
      of this article is to describe the development of a community-based intervention
      aimed at promoting physical activity and healthy eating among people aged 55
      years and over, in a socioeconomically disadvantaged community. The Intervention
      Mapping protocol was used to develop the intervention. We conducted a literature
      search, consultation with community partners and inhabitants, and a quantitative
      study, in order to obtain insight into the determinants of the target population
      and to identify appropriate theory-based methods and practical strategies for
      behavioural change. An assessment was performed of the problem with respect to
      health behaviour and the underlying determinants. Findings were translated into
      program, performance and change objectives which specify determinants related to
      behavioural change. Theory-based methods and practical applications were
      selected, resulting in a plan for adoption and implementation. The intervention
      included a local media campaign, social environmental approaches and physical
      environmental activities in the community, with an intermediating role for
      inhabitants and health professionals in the promotion of the campaign. An
      evaluation plan was produced to evaluate the effectiveness of the intervention.
      The Intervention Mapping protocol was a helpful instrument in developing a
      feasible, theory and evidence-based intervention tailored to a specific target
      population in the area of health promotion. The systematic and structured
      approach provided insight into the relationship between the objectives, methods
      and strategies used to develop the comprehensive intervention.

PMID- 29590353
TI  - Percutaneous aspiration of calcium debris resulting in coronary artery occlusion
      after aortic valve replacement.

PMID- 29590354
TI  - Complex automated medication systems reduce medication administration errors in a
      Danish acute medical unit.
AB  - Objective: The objective of this study was to evaluate the effectiveness of two
      automated medication systems in reducing medication administration errors.
      Design: The study was a controlled before-and-after study and included three
      observation periods with collection of data during a 3-week period as initial
      baseline and two subsequent follow-up periods at 10 and 20 months. Setting: The
      study was conducted in two Danish acute medical units. Interventions: Two
      automated medication systems were implemented: (i) a complex automated medication
      system (cAMS) consisting of an automated dispensing cabinet, automated unit-dose
      dispensing and barcode medication administration (BCMA) and (ii) a non-patient
      specific automated medication system (npsAMS) consisting of automated unit-dose
      dispensing and BCMA. Main outcome measure: The occurrence of administration
      errors and sub-types; procedural and clinical errors were observed. The
      proportion of errors was calculated by dividing the number of doses with one or
      more errors with the number of opportunities for errors. Difference-in-difference
      analysis using logistic regression was used to assess changes in proportion of
      errors. Results: Compared with control, the cAMS reduced the overall risk of
      administration errors in the intervention unit, (odds ratio (OR) 0.53; 95%
      confidence interval (CI) 0.27-0.90) and procedural errors were significantly
      reduced as well (OR 0.44; 95% CI 0.126-0.94). The npsAMS effectively reduced the
      clinical errors in the intervention ward (OR 0.38; 95% CI 0.15-0.96).
      Conclusions: In line with previous research, this study found that technological
      interventions in the medication administration process could reduce the
      occurrence of medication errors.

PMID- 29590355
TI  - Essential Resources and Strategies for Antibiotic Stewardship Programs in the
      Acute Care Setting.
AB  - Background: Antibiotic stewardship programs improve clinical outcomes and patient
      safety and help combat antibiotic resistance. Specific guidance on resources
      needed to structure stewardship programs is lacking. This manuscript describes
      results of a survey of US stewardship programs and resultant recommendations
      regarding potential staffing structures in the acute care setting. Methods: A
      cross-sectional survey of members of 3 infectious diseases subspecialty societies
      actively involved in antibiotic stewardship was conducted. Survey responses were
      analyzed with descriptive statistics. Logistic regression models were used to
      investigate the relationship between stewardship program staffing levels and self
      reported effectiveness and to determine which strategies mediate effectiveness.
      Results: Two-hundred forty-four respondents from a variety of acute care settings
      completed the survey. Prior authorization for select antibiotics, antibiotic
      reviews with prospective audit and feedback, and guideline development were
      common strategies. Eighty-five percent of surveyed programs demonstrated
      effectiveness in at least 1 outcome in the prior 2 years. Each 0.50 increase in
      pharmacist and physician full-time equivalent (FTE) support predicted a 1.48-fold
      increase in the odds of demonstrating effectiveness. The effect was mediated by
      the ability to perform prospective audit and feedback. Most programs noted
      significant barriers to success. Conclusions: Based on our survey's results, we
      propose an FTE-to-bed ratio that can be used as a starting point to guide
      discussions regarding necessary resources for antibiotic stewardship programs
      with executive leadership. Prospective audit and feedback should be the
      cornerstone of stewardship programs, and both physician leadership and
      pharmacists with expertise in stewardship are crucial for success.

PMID- 29590356
TI  - Evaluating the quality of antenatal care and pregnancy outcomes using content and
      utilization assessment.
AB  - Objective: To assess the adequacy of antenatal care (ANC) and its association
      with pregnancy outcomes using an approach that includes adequacy of both
      utilization and content. Design: Retrospective cohort study. Setting and
      Participants: Women attending ANC at public-funded primary health clinics where
      data were extracted from individual records. Methods: Adequacy of utilization
      assessment was based on the concept of Adequacy of Prenatal Care Utilization
      index; adequacy of content assessed the recommended routine care received by the
      women according to local guidelines. Association between adequacy and pregnancy
      outcomes was examined using binary logistic regression. Main Outcome Measures:
      Pregnancy outcomes included preterm birth and low birth weight. Results: Sixty
      three percent of women showed higher than recommended ANC utilization; 52% had
      <80% of recommended routine care content. Although not statistically significant,
      the odds of preterm birth was lower among women with adequate level of
      utilization compared with inadequate (adjusted odds ratios (aOR) = 2.34, 95%
      confidence interval (CI) 0.45-12.16) and intensive levels (aOR = 3.27, 95% CI
      0.73-14.60). Regarding adequacy of content, women who received inadequate level
      of care content were associated with higher prevalence of preterm birth (aOR =
      3.69, 95% CI 1.60-8.55). Conclusion: The study shows inadequate content is
      associated with higher prevalence of preterm birth and suggests that inadequate
      utilization increases the risk of preterm birth. It demonstrates the relevance of
      using both utilization and content assessment in evaluating quality of ANC.
      Further studies are encouraged to review the methods used.

PMID- 29590357
TI  - Hip Fractures in People Older Than 95 Years: Are Patients Without Age-Associated
      Illnesses Different?
AB  - Background: Patients older than 95 years of age can be categorized according to
      three morbidity profiles: escapers, delayers, and survivors. The aim of this
      study was to describe the baseline characteristics, in-hospital outcomes, and
      cumulative mortality of extremely elderly patients admitted with hip fractures
      and to examine whether there were differences between patients without age
      related illnesses (escapers) and others in the same age group (survivors when age
      associated illnesses were diagnosed before the age of 80, delayers when these
      illnesses appeared after the age of 80). Methods: A retrospective review of
      clinical and outcome data of all patients older than 95 years of age admitted
      with hip fractures. Results: Two hundred patients older than 95 years were
      admitted with hip fractures between December 2009 and September 2015. Eighty-six
      per cent of patients had at least one in-hospital complication. In-hospital
      mortality was 12.5 per cent; cumulative mortality rates at 30 days, 3 months, and
      1 year were 20.3, 30.8, and 50.5 per cent, respectively. There were 15 (7.5%)
      escaper patients. Compared with other patients with age-related illnesses, they
      took fewer drugs, had lower Charlson scores, a higher Barthel index score,
      shorter length of hospital stay, less delay in surgery, and more often required
      discharge to an in-patient rehabilitation facility. No differences in cumulative
      mortality were noted. Conclusions: Escaper patients had better baseline
      characteristics, shorter length of hospital stay, and delay in surgery.
      Nevertheless, their in-hospital and cumulative mortality rates were similar to
      those of other patients older than 95 years.

PMID- 29590358
TI  - Gene Expression Classifier vs Targeted Next-Generation Sequencing in the
      Management of Indeterminate Thyroid Nodules.
AB  - Context: Molecular testing has reduced the need for diagnostic hemithyroidectomy
      for indeterminate thyroid nodules. No studies have directly compared molecular
      testing techniques. Objective: Compare the diagnostic performance of Afirma Gene
      Expression Classifier (GEC) with that of ThyroSeq v2 next-generation sequencing
      assay. Design: Parallel randomized trial, monthly block randomization of patients
      with Bethesda III/IV cytology to GEC or ThyroSeq v2. Setting: University of
      California, Los Angeles. Participants: Patients who underwent thyroid biopsy
      (April 2016 to June 2017). Intervention: Testing with GEC or ThyroSeq v2. Main
      Outcome Measure: Molecular test performance. Results: Of 1372 thyroid nodules,
      176 (13%) had indeterminate cytology and 149 of 157 eligible indeterminate
      nodules (95%) were included in the study. Of nodules tested with GEC, 49% were
      suspicious, 43% were benign, and 9% were insufficient. Of nodules tested with
      ThyroSeq v2, 19% were mutation positive, 77% were mutation negative, and 4% were
      insufficient. The specificities of GEC and ThyroSeq v2 were 66% and 91%,
      respectively (P = 0.002); the positive predictive values of GEC and ThyroSeq v2
      were 39% and 57%, respectively. Diagnostic hemithyroidectomy was avoided in 28
      patients tested with GEC (39%) and 49 patients tested with ThyroSeq v2 (62%).
      Surveillance ultrasonography was available for 46 nodules (45 remained stable).
      Conclusions: ThyroSeq v2 had higher specificity than Afirma GEC and allowed more
      patients to avoid surgery. Long-term surveillance is necessary to assess the
      false-negative rate of these particular molecular tests. Further studies are
      required for comparison with other available molecular diagnostics and for newer
      tests as they are developed.

PMID- 29590359
TI  - Right coronary artery arising within an aorta-to-left ventricle tunnel: surgical
      repair in a neonate.
AB  - We herein describe the successful surgical repair of a very rare combination of
      an aorta-to-left ventricle tunnel with the right coronary artery arising from it.
      The neonate presented with signs of heart failure due to significant
      regurgitation of blood via the tunnel. The closure of the tunnel was feasible
      during neonatal period without patches.

PMID- 29590360
TI  - Metabolites of endophytic fungi from Australian native plants as potential
      anticancer agents.
AB  - Interest in endophytes as natural sources for new medicines was inspired by the
      discovery of paclitaxel-producing endophytic fungi. This study investigated the
      anti-cancer activity of extracts of endophytes isolated from two Australian
      plants, Eremophila longifolia (EL) and Eremophila maculata (EM). Endophytes were
      isolated from surface-sterilised leaf tissue, grown as pure cultures and
      identified by sequencing of Internal Transcribed Spacer (ITS) regions of the
      ribosomal DNA. To determine cytotoxicity, two leukaemic (MOLT-4, T-cell
      leukaemia; PreB-697, Pre-B leukaemia), a lung cancer cell line (A549) and a
      normal human fibroblast cell line were treated with endophyte extracts to assess
      cytotoxicity in relation to alternariol monomethyl ether (AME) and alternariol
      (AOH). Endophyte extracts that showed cell cytotoxicity were analysed by UV-HPLC
      to determine the metabolites. Pure AME and AOH, three extracts form Alternaria
      sp. (EM-6, EM-7 and EM-9) and one from Preussia minima (EL-14) were cytotoxic to
      the cancer cell lines. All cytotoxic endophytes contained AME and AOH, the most
      cytotoxic endophyte EM-6 also contained two unique peaks. These data indicate
      that these four endophyte extracts may have anti-cancer properties due to the
      presence of AME and AOH; however, the unique compounds found in the EM-6 extract
      may be exclusively cytotoxic and warrant further investigation.

PMID- 29590361
TI  - Cell type discovery using single-cell transcriptomics: implications for
      ontological representation.
AB  - Cells are fundamental function units of multicellular organisms, with different
      cell types playing distinct physiological roles in the body. The recent advent of
      single-cell transcriptional profiling using RNA sequencing is producing 'big
      data', enabling the identification of novel human cell types at an unprecedented
      rate. In this review, we summarize recent work characterizing cell types in the
      human central nervous and immune systems using single-cell and single-nuclei RNA
      sequencing, and discuss the implications that these discoveries are having on the
      representation of cell types in the reference Cell Ontology (CL). We propose a
      method, based on random forest machine learning, for identifying sets of
      necessary and sufficient marker genes, which can be used to assemble consistent
      and reproducible cell type definitions for incorporation into the CL. The
      representation of defined cell type classes and their relationships in the CL
      using this strategy will make the cell type classes being identified by high
      throughput/high-content technologies findable, accessible, interoperable and
      reusable (FAIR), allowing the CL to serve as a reference knowledgebase of
      information about the role that distinct cellular phenotypes play in human health
      and disease.

PMID- 29590362
TI  - Frailty as a predictor of mortality and hospital services use in older adults: a
      cluster analysis in a cohort study.
AB  - Background: Lowering mortality and hospitalization of older adults is one of the
      main goals of public health to improve both health systems' sustainability and
      older adults' quality of life. The aim of this study is to identify the
      determinants associated with mortality and the use of hospital services in the
      population older than 64 years of age. Methods: A randomized sample from the
      population of the Lazio region (Italy) above the age of 64 was enrolled in 2014
      by the administration of a questionnaire to assess frailty; the rates of use of
      hospital services and mortality in the year following the enrolment have been
      retrieved by the regional database. Univariable and multivariable analyses
      addressed the association of health status, social and economic variables with
      health outcomes. Results: One thousand two hundred and eighty persons were
      recruited; 52 deaths were reported at 1 year of follow-up (robust 1.8%, frail
      10.1% and very frail 19.1%, P < 0.001). The mean rate of use of hospital services
      was 692.2 per 1000 observation/year (robust 589.5, frail 1191.1 and very frail
      848.4, P < 0.001). In the multivariate analysis, the higher rate of use of
      hospital services was independently associated with functional status, social
      support, psychological/psychiatric discomfort, availability of home care services
      and physical health. Conclusions: Frailty, as a multidimensional issue, is also a
      strong predictor of survival in the short term. The use of the hospital services
      by older adults is associated mainly with functional status, social resources,
      psycho-physical status and health service organization factors.

PMID- 29590363
TI  - The intergenerational consequences of war: anxiety, depression, suicidality, and
      mental health among the children of war veterans.
AB  - Background: The long-term effects of military deployment on the mental health of
      war veterans have been investigated extensively, but few studies have examined
      the long-term impact of parental deployment on children's mental health. Methods:
      Using a retrospective, multigenerational survey and propensity score analysis to
      adjust for selection effects and endogeneity bias, we investigated the impact of
      parental deployment on the mental health of the adult children of Australian
      veterans of the Vietnam War. We analysed data from 1966 adult men (35%) and women
      (65%) whose fathers (N = 1418) were selected at random from the population of
      surviving men who served in the Australian army during the Vietnam War (1962-75).
      Mean age of respondents was 37. The main outcome measures were self-reported
      diagnosis or treatment for anxiety and depression (i.e. lifetime and previous 12
      months), suicidality based on Psychiatric Symptom Frequency Scale, and current
      mental health as measured by the Mental Health Inventory of the SF-36. The key
      independent variable was whether their fathers were deployed to the Vietnam War.
      Results: Almost 40 years after the war, the adult children of deployed veterans
      were more likely to have been diagnosed with anxiety [odds ratio (OR) = 1.54,
      confidence interval (CI) = 1.04, 2.28] and depression (OR = 1.77, CI = 1.03,
      3.05), to have had thoughts of suicide and self-harm (OR = 2.39, CI = 1.57, 3.65)
      and to have made suicidal plans (OR = 3.52, CI = 1.40, 8.85) than the offspring
      of comparable, non-deployed army veterans. They also reported poorer current
      mental health (Coefficient = -5.08, CI = -6.60 - -3.56). Conclusions: The results
      imply that there are significant and enduring adverse effects of parental
      deployment on the mental health of children in military families, and provide
      some insight into the potential long-term impacts of recent military engagements
      in Afghanistan and Iraq.

PMID- 29590364
TI  - When is quitting an escape? How different job demands affect physical and mental
      health outcomes of retirement.
AB  - Background: The demographic aging of societies and the need to adapt to this
      trend makes it important to gain insight into the way retirement affects
      different forms of health, and factors that influence this relationship. Pre
      retirement job characteristics have only rarely been included in this type of
      research. Methods: The regressor variable method is applied to two waves (4 and
      5) of data from the Survey of Health Ageing and Retirement in Europe, a multi
      national prospective cohort study. The final sample consists of 9092 people aged
      50-70 at wave 4, of whom 1257 retired voluntarily. Health is assessed through the
      presence of physical health problems, general self-rated health and the EURO-D
      scale for depressive symptoms. Results: The findings indicate that retirement
      from jobs with high physical demands leads to a relative improvement in general
      self-rated health compared with those who remain at work. Retirement from a
      psychologically demanding job is associated with less depressive symptoms. No
      effects are found for health measured as the presence of physical health
      problems. Conclusion: Different types of measures for health yield different
      results for outcomes of retirement; pre-retirement job demands play an important
      role in how retirement affects health; physical demands seem primarily related to
      physical health benefits, psychological demands seem primarily related to mental
      health benefits.

PMID- 29590365
TI  - A quality improvement project to increase self-administration of medicines in an
      acute hospital.
AB  - Quality problem or issue: A patient survey found significantly fewer patients
      reported they had self-administered their medicines while in hospital (20% of 100
      patients) than reported that they would like to (44% of 100). We aimed to make
      self-administration more easily available to patients who wanted it. Initial
      assessment: We conducted a failure, modes and effects analysis, collected
      baseline data on four wards and carried out observations. Choice of solution: Our
      initial assessment suggested that the main areas we should focus on were raising
      patient awareness of self-administration, changing the patient assessment process
      and creating a storage solution for medicines being self-administered. We
      developed new patient information leaflets and posters and a doctor's assessment
      form using Plan-Do-Study-Act cycles. We developed initial designs for a storage
      solution. Implementation: We piloted the new materials on three wards; the fourth
      withdrew due to staff shortages. Evaluation: Following collection of baseline
      data, we continued to collect weekly data. We found that the proportion of
      patients who wished to self-administer who reported that they were able to do so,
      significantly increased from 41% (of 155 patients) to 66% (of 118 patients)
      during the study, despite a period when the hospital was over capacity. Lessons
      learned: Raising and maintaining healthcare professionals' awareness of self
      administration can greatly increase the proportion of patients who wish to self
      administer who actually do so. Healthcare professionals prefer multi-disciplinary
      input into the assessment process.

PMID- 29590367
TI  - Selective visceral perfusion improves renal flow and hepatic function in neonatal
      aortic arch repair.
AB  - OBJECTIVES: The aortic arch repair in the neonatal period is a complex procedure
      with significant morbidity. We define a useful double-perfusion technique and its
      effect on the function of abdominal organs in the postoperative course. METHODS:
      Nine patients with double perfusion (Group 1) were compared with 14 patients with
      antegrade cerebral perfusion (Group 2). The objective was to discern the
      incidence of postoperative acute kidney injury and impaired hepatic function, as
      well as tissue perfusion and myocardial function parameters. Mechanical
      ventilation time, postoperative length of stay and 30-day mortality were
      measured. We excluded patients with extracorporeal membrane oxygenation, early
      mortality (<72 h) and preoperative renal or hepatic insufficiency. RESULTS: Nine
      (39%) patients developed postoperative acute kidney injury, with 22% (n = 2) in
      Group 1 and 50% (n = 7) in Group 2 (P = 0.183). A higher urine output was
      observed during the first 24 h for Group 1 (P = 0.032). Eleven patients developed
      impaired hepatic function in the immediate postoperative period: 2 (18.2%) in
      Group 1 and 9 (81.8%) in Group 2 (P = 0.04). The international normalized ratio
      (P = 0.006-0.031) and prothrombin time (P = 0.007-P = 0.016) were significantly
      lower in the double-perfusion group during the first 72 h. Significant difference
      was observed in lactate levels in the first 72 h (P = 0.001-0.009). There was no
      postoperative mortality in either group. CONCLUSIONS: Selective visceral
      perfusion is a safe procedure that provides a better urine output, hepatic
      function and tissue perfusion. This technique allows for the repair of complex
      aortic arch anomalies in neonates without deep hypothermic circulatory arrest.

PMID- 29590366
TI  - 'Drug adherence levels are falling down again': health worker perceptions of
      women's service utilization before and after integration of HIV/AIDS services
      into general care in India.
AB  - Integrated models of HIV/AIDS service delivery are believed to have advantages
      over stand-alone models of care from health planners' and providers'
      perspectives. Integration models differ, yet there is little information about
      the influence of differing models on workers' beliefs about models' efficacy.
      Here, we examine the effect of integration of HIV care into the general health
      system in India. In 2014, India replaced its stand-alone model of HIV service
      delivery-Community Care Centers (CCCs)-with a purported integrated model that
      delivers HIV medical services at general hospitals and HIV psychosocial services
      at nearby Care and Support Centers (CSCs). We examine 15 health workers'
      perceptions of how change from the earlier stand-alone model to the current model
      impacted women's care in a district in Uttar Pradesh, India. Results indicate
      that (1) Women's antiretroviral (ART) adherence and utilization of psychosocial
      support service for HIV/AIDS suffered when services were not provided at one
      site; (2) Provision of inpatient care in the CCC model offered women living in
      poverty personal safety in accessing HIV health services and promoted chances of
      competent ART usage and repeat service utilization; and (3) Although integration
      of HIV services with the general health system was perceived to improve patient
      anonymity and decrease chances of HIV-related stigma and discrimination, resource
      shortages continued to plague the integrated system while shifting costs of time
      and money to the patients. Findings suggest that integration efforts need to
      consider the context of service provision and the gendered nature of access to
      HIV care.

PMID- 29590368
TI  - Developing patient safety system using WHO tool in hospitals in Oman.
AB  - Objective: Oman is progressively implementing the Patient Safety Friendly
      Hospital Initiative (PSFHI), a tool formulated by the World Health Organization
      (WHO) to achieve optimal patient safety in hospitals. This paper describes its
      implementation in selected government and private hospitals in Oman and analyses
      the performance of four hospitals whose implementations of PSFHI were assessed by
      WHO. Design: The PSFHI initiative was launched in 11 hospitals in Oman during
      2016. The enrolled hospitals implemented a 1-year plan composed of several steps
      such as formation of steering committees, working groups, full orientation about
      the standards, training of staff, documents development and community
      involvement. One year later, four hospitals which were the earliest to join the
      initiative were subjected to WHO assessment. Setting: Secondary level government
      and private hospitals. Intervention(s): The WHO-PSFHI standards. Main Outcome
      Measure: Hospitals' adherence to the standards. Results: Three of the four
      hospitals (one government and two private) scored level two. One government
      hospital scored level three, earning it the distinction of being the first
      hospital in the Eastern Mediterranean Region to reach level three in the very
      first assessment. Conclusions: Implementation of PSFHI in selected hospitals of
      Oman had successful outcomes in improving patient's safety.

PMID- 29590369
TI  - Rotation of the outflow tracts.
AB  - The optimal treatment for transposition of the great arteries with stenosis along
      the pulmonary tract has always been a challenge. En bloc rotation of the truncus
      arteriosus has been proposed as an alternative method in this group of patients.
      We report a truncus turnover in a 3-month-old, 3.4 kg infant.

PMID- 29590370
TI  - KPC-2 carbapenemase-producing Pseudomonas aeruginosa reaching Germany.
AB  - Background: Antimicrobial resistance due to carbapenemase expression poses a
      worldwide threat in healthcare. Inter-genus exchange of genetic information is of
      utmost importance in this context. Objectives: Here, to the best of our
      knowledge, we describe the first detection and characterization of a KPC-2
      producing Pseudomonas aeruginosa in Germany. Methods: Characterization of the
      isolate was performed using MALDI-TOF MS, automated microdilution and MLST.
      Carbapenemase detection was performed using phenotypic and genotypic assays. The
      blaKPC-2-carrying plasmid was transformed into Escherichia coli NEB(r) 10-beta.
      The purified plasmid DNA was sequenced using the Illumina technique. Results: The
      isolate expressed ST235 and was resistant to carbapenems. Antimicrobial
      susceptibility testing revealed colistin to be the only antimicrobial agent
      active in vitro. The blaKPC-2 gene was located on a replicon type lncHI1 plasmid
      as part of Tn4401. Conclusions: The first detection (to the best of our
      knowledge) of plasmid-encoded KPC-2 in P. aeruginosa in Germany may point to a
      currently underestimated spread of carbapenemases among clinically relevant Gram
      negative bacteria. Here, to the best of our knowledge, we also provide the first
      report of blaKPC-2 associated with the IncHI1 plasmid.

PMID- 29590371
TI  - Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-analysis of
      Prospective Interventional Studies.
AB  - Introduction: Somatostatin analogs (SSAs) effectivelycontrol growth hormone
      secretion in first and second line treatmentof acromegaly. Their effect onglucose
      metabolism is still debated. Aim: to address the following questions: 1) Do SSAs
      affect fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated
      hemoglobin (HbA1c), glucose load (2h-OGTT), HOMA-I, HOMA-beta, triglycerides
      (TGD), weight (W) or body mass index (BMI)? 2) Do lanreotide (LAN) and octreotide
      LAR (OCT) affect metabolism differently? 3)Does their effect depend on disease
      control? Methods: We performed a meta-analysis of prospective interventional
      trialstreating acromegaly with SSAs. Inclusion criteria: all studies reporting
      glyco-metabolic outcomes before and after SSAs with a minimum 6-month follow-up.
      Results: The inclusion criteria were met by 47 studies treating 1297 subjects
      (631 F). SSA treatment effectively lowered FPI (effect size [ES] -6.67 mU/L,
      95%CI: -8.38 to -4.95mU/L; p<0.001), HOMA-I (ES -1.57, CI: -2.42 to -0.72;
      p<0.001), HOMA-beta (ES -47.45, CI: -73.15 to -21.76; p<0.001) and TGD (ES -0.37
      mmol/L, CI: -0.47 to -0.27 mmol/L; p<0.001). SSAs worsened 2h-OGTT (ES 0.59
      mmol/L, CI: 0.05 to 1.13 mmol/L; p=0.032), but not FPG. A mild but significant
      increase in HbA1c (ES 0.12%, CI: 0.00to 0.25%; p=0.044) was found in OCT treated
      subjects. Conclusions: SSA treatment in acromegaly patients-while improving
      disease control- reduces insulin levels, increases after load glucose and,
      ultimately, increases HbA1c levels without affecting FPG. The findings suggest
      that clinicians treating acromegaly with SSAs should consider targeting post
      prandial glucose.

PMID- 29590372
TI  - Expression Profiles and Functional Characterization of Two Odorant-Binding
      Proteins From the Apple Buprestid Beetle Agrilus mali (Coleoptera: Buprestidae).
AB  - The apple buprestid beetle, Agrilus mali Matsumura (Coleoptera: Buprestidae), can
      respond to various volatiles, but the underlying mechanism of odorant perception
      for this insect is poorly understood. Here, we cloned A. mali's odorant-binding
      proteins 3 (AmalOBP3) and 8 (AmalOBP8) and characterized their expression
      patterns and binding profiles. Sequence and phylogenetic analyses showed that
      AmalOBP3 and AmalOBP8 were distributed in the classic and minus-C OBP subfamily,
      respectively. AmalOBP3 was specifically and abundantly expressed in antennae of
      both sexes. AmalOBP8 displayed high transcript levels in antennae of both sexes,
      abdomens of males, and wings of both sexes. Both AmalOBPs exhibited much higher
      expression in male antennae than in female antennae, suggesting that they could
      be important in perception of male-specific olfactory cues (e.g., some sex
      pheromones). Out of the 40 odorant ligands tested, AmalOBP3 and AmalOBP8 bound to
      15 and 21 different odorants, respectively, indicating a distinct and selective
      binding profile for them. Both AmalOBPs seemed to have very strong binding
      affinity to aliphatic alcohols and aldehydes with 12 to 15 carbon atoms.
      Alcohols, esters, and terpenoids were more likely to be good ligands for both
      AmalOBPs than aldehydes and alkanes. Together with its broad expression in
      different tissues, strong binding with higher numbers of putative ligands for
      AmalOPB8 means that this protein can have more extensive functional roles in
      chemosensation of A. mali. Our results provide insights into the molecular basis
      of chemosensation in A. mali, as well as a basis for developing detection,
      monitoring, and management tools for this serious pest.

PMID- 29590373
TI  - Certification ISO 9001 in clinical ethics consultation for improving quality and
      safety in healthcare.
AB  - This paper refers to the quality management process of the Laboratory of Clinical
      Bioethics (LCB) of the University of Padua (Italy), which has obtained the
      quality certification to ISO 9001:2008, as a Clinical Ethics Support Service. Its
      activities consist mainly in clinical ethics consultations and training services,
      addressed to those who are called to decisions with ethical implications in the
      clinical setting, proposing a structured approach to identify and analyze the
      ethical issues that may loom in the relationships between health professionals
      and patients, and participating in their solution. The expected benefits of the
      application of ISO 9001 were mainly the following: to formalize the procedure
      adopted for clinical ethics consultation and training, to obtain a controlled
      management of documents, information and data, to ensure and demonstrate the
      quality of the provided activities and to make methods and organization publicly
      available. The main results which have been achieved with the 'quality management
      project' are summarized as follows: the enunciation of LCB Mission and Quality
      Policy; the drafting of the procedure by which clinical ethics consultation is
      provided; the formalization of members' skills and the adoption of relevant
      process and outcome indicators. Our experience may be useful in promoting
      accountability for the quality of ethics consultation services. We consider the
      certification process as a tool for transparent and reliable management of one of
      the most critical tasks in the current context of healthcare, motivating similar
      facilities to undertake similar pathways, with the aim to provide quality control
      on their activities.

PMID- 29590374
TI  - Corrigendum to "Connective Tissue Growth Factor and its Role in Lung
      Adenocarcinoma Invasion and Metastasis".

PMID- 29590375
TI  - Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2
      diabetes in PCOS: a systematic review and meta-regression.
AB  - BACKGROUND: Our prior meta-analyses demonstrated an increased prevalence of
      impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with
      polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity.
      OBJECTIVE AND RATIONALE: We aimed to update our previous review to quantify the
      prevalence of IGT and T2DM in PCOS with only quality studies (good and fair
      quality). We also aimed to examine the contribution of parameters including
      ethnicity, obesity and method of diagnosing T2DM in explaining the observed
      heterogeneity in IGT and T2DM prevalence in PCOS. SEARCH METHODS: We conducted a
      literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand
      searching) up to June 2016 to identify studies reporting the prevalence of
      dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies
      where women with PCOS (defined according to original National Institute of
      Health) were compared to women without PCOS for the end-points of the prevalence
      of IGT or T2DM. We excluded case reports, case series, editorials, and narrative
      reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM
      were measured by fasting glucose, only were excluded. We assessed the
      methodological quality of the included studies using a priori criteria based on
      the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented
      as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel
      methods. We assessed the contribution of demographic and clinical factors to
      heterogeneity using subgroup and meta-regression analysis. OUTCOMES: We reviewed
      4530 studies and included 40 eligible studies in the final analysis. On meta
      analysis of quality studies, women with PCOS had an increased prevalence of IGT
      (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which
      differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3
      fold), was higher with obesity, and doubled among studies using self-report or
      administrative data for diagnosing diabetes. The ethnicity-related difference
      retained its significance for Asia and Europe in BMI-matched subgroups. Clear
      contributors to heterogeneity did not emerge in meta-regression. WIDER
      IMPLICATIONS: Our findings underscore the importance of PCOS as a cause of
      dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance
      of ethnicity and obesity and emphasize the need for accurate diagnostic methods
      for diabetes. PROSPERO REGISTRATION NUMBER: CRD42017056524.

PMID- 29590376
TI  - Incidence of Nephrotoxicity Among Pediatric Patients Receiving Vancomycin With
      Either Piperacillin-Tazobactam or Cefepime: A Cohort Study.
AB  - Background: Recent studies in adults have found an incidence of acute kidney
      injury (AKI) in patients treated with a combination of vancomycin and
      piperacillin-tazobactam (TZP) that is greater than that expected with either
      medication alone. The purpose of this study was to determine whether combination
      therapy with vancomycin and TZP is associated with an incidence of AKI in
      pediatric patients higher than that in those on combination therapy with
      vancomycin and cefepime. Methods: We performed a retrospective single-center
      matched-cohort study of pediatric patients who received vancomycin in combination
      with TZP or cefepime between January 2015 and June 2016. The patients were
      matched according to chronic disease, age, sex, and number of concomitant
      nephrotoxic medications at the time of combination antibiotic therapy. The
      primary outcome was incidence of AKI. Secondary outcomes included differences
      between groups in time to AKI, resolution of AKI, and effect of vancomycin trough
      levels on the incidence of nephrotoxicity. Conditional logistic regression was
      used to compare categorical and continuous variables between treatment groups.
      Conditional Poisson regression was used to assess the association between AKI and
      treatment groups. Stratified log-rank tests and Cox proportional hazards models
      with shared frailty were used to compare the times to AKI according to treatment
      group. Results: Two hundred twenty-eight matched patients were included. AKI
      developed in 9 (7.9%) of 114 and 33 (28.9%) of 114 patients in the cefepime and
      TZP groups, respectively (P < .001). Type of combination therapy remained a
      significant predictor for AKI in multivariate conditional Poisson analysis in
      which adjustments were made for age, sex, use of concomitant nephrotoxins, and
      vancomycin dose (relative risk, 2.5 [95% confidence interval, 1.1-5.8]; P = .03).
      AKI developed almost 3 times sooner in the TZP group than in the cefepime group
      (hazard ratio, 2.9 [95% confidence interval, 1.3-6.1]; P = .006). Sensitivity
      analyses in which adjustment was made for antibiotic indication in addition to
      the aforementioned variables and excluding those with gastrointestinal infection
      revealed similar results. Conclusion: Among hospitalized children at our
      institution, combination therapy with vancomycin and TZP was associated with an
      incidence of AKI higher than that associated with vancomycin and cefepime.

PMID- 29590377
TI  - Serum vitamin D levels among children aged 0-12 years in the First Affiliated
      Hospital of Harbin Medical University, China.
AB  - Background: Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are
      highly prevalent in the world, but the vitamin D status of children in northeast
      China is seldom investigated. The aim of this study was to clarify the prevalence
      of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical
      University in Heilongjiang province in China. Methods: We collected data from
      9795 children who were outpatients aged 0-12 years who visited the First
      Affiliated Hospital of Harbin Medical University from September 2014 to August
      2016. Serum 25-hydroxy vitamin D [25(OH)D] levels were determined by
      chemiluminescent immunoassay and categorized as <20, 20-30 and >30 ng/mL.
      Results: The highest mean level of serum 25(OH)D was found at the 1-3 years stage
      (31.14 ng/mL) and the lowest at 6-12 years stage (18.58 ng/mL). The mean serum
      25(OH)D level among school girls (17.86 ng/mL) was lower than that of boys (19.12
      ng/mL). The prevalence of vitamin D sufficiency during 2014 was only 17.2%, but
      increased to ~45% in 2016. Conclusions: The prevalence of VDD and insufficiency
      among children in the First Affiliated Hospital of Harbin Medical University is
      high, especially among children aged 6-12 years.

PMID- 29590378
TI  - Effect of Relaxation of Deltamethrin Pressure on Metabolic Resistance in a
      Pyrethroid-Resistant Aedes aegypti (Diptera: Culicidae) Strain Harboring Fixed
      P989P and G1016G kdr Alleles.
AB  - Mutation of the voltage-gated sodium channel genes or knockdown resistance (kdr)
      and metabolic resistance in Aedes aegypti (L.) (Diptera: Culicidae) are important
      resistance mechanisms against pyrethroids. The present study investigated the
      effect of relaxation of deltamethrin selection pressure on the level of mixed
      function oxidases (MFO), when the allele frequency of S989P+V1016G mutations is
      fixed in a resistant Ae. aegypti strain (UPK-R) from Chiang Mai, Thailand. The
      mosquitoes were divided into two groups, exposure and nonexposure groups, and
      maintained for 12 generations in an insectary room. Adults of the exposure group
      (F3 to F12) were treated with 0.05% deltamethrin-impregnated papers. The median
      lethal concentrations (LC50) of deltamethrin of larvae were determined by World
      Health Organization (WHO) bioassay. MFO activity was determined in F0 and F12.
      The results revealed that there was a decreasing trend of adult mortality rates
      in the exposure group over time. The larval LC50 values of the exposure group
      were gradually increased, whereas those of the nonexposure group were gradually
      decreased. The level of MFO activity in the nonexposure group (F12) was lower
      than the parent and exposure groups (F12) by 1.5 and 4-fold in the larvae,
      respectively, and 1.5 and 2.5-fold in the adult females, respectively. However,
      the frequency of P989+G1016 alleles in both groups was 100% up to F12 when the
      experiment ended. This study indicates that there was a significant but small
      reduction in the activity levels of MFOs when pyrethroid selection pressure is
      relaxed in this kdr strain of Ae. aegypti.

PMID- 29590379
TI  - Increased Plasma Proneurotensin Levels Identify NAFLD in Adults With and Without
      Type 2 Diabetes.
AB  - Context: Neurotensin (NT), an intestinal peptide released by fat ingestion,
      promotes lipid absorption; higher circulating NT levels are associated with type
      2 diabetes (T2D), obesity, and cardiovascular disease. Whether NT is related to
      nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
      has not been fully investigated. Objective: To study the relationship between
      plasma proneurotensin 1 to 117 (pro-NT), a stable fragment of the NT precursor
      hormone, and the presence/severity of NAFLD/NASH and to unravel correlates of
      increased pro-NT levels. Design/Setting/Participants: For this cross-sectional
      study, 60 obese individuals undergoing bariatric surgery for clinical purposes
      were recruited. The association between pro-NT and NAFLD was further investigated
      in 260 consecutive subjects referred to our outpatient clinics for metabolic
      evaluations, including liver ultrasonography. The study population underwent
      complete metabolic characterization; in the obese cohort, liver biopsies were
      performed during surgery. Main Outcome Measures: Plasma pro-NT levels in relation
      to NAFLD/NASH. Results: Obese subjects with biopsy-proven NAFLD (53%) had
      significantly higher plasma pro-NT than those without NAFLD (183.6 +/- 81.4 vs
      86.7 +/- 56.8 pmol/L, P < 0.001). Greater pro-NT correlated with NAFLD presence
      (P < 0.001) and severity (P < 0.001), age, female sex, insulin resistance, and
      T2D. Higher pro-NT predicted NAFLD with an area under receiver operating
      characteristic curve of 0.836 [95% confidence interval (CI), 0.73 to 0.94; P <
      0.001]. Belonging to the highest pro-NT quartile correlated with increased NAFLD
      risk (odds ratio, 2.62; 95% CI, 1.08 to 6.40) after adjustment for confounders.
      The association between higher pro-NT and NAFLD was confirmed in the second
      cohort independently from confounders. Conclusions: Increased plasma pro-NT
      levels identify the presence/severity of NAFLD; in dysmetabolic individuals, NT
      may specifically promote hepatic fat accumulation through mechanisms likely
      related to increased insulin resistance.

PMID- 29590380
TI  - Screening for Moral Injury: The Moral Injury Symptom Scale - Military Version
      Short Form.
AB  - Introduction: To develop a short form (SF) of the 45-item multidimensional Moral
      Injury Symptom Scale - Military Version (MISS-M) to use when screening for moral
      injury and monitoring treatment response in veterans and active duty military
      with PTSD. Methods: A total of 427 veterans and active duty military with PTSD
      symptoms were recruited from VA Medical Centers in Augusta, GA; Los Angeles, CA;
      Durham, NC; Houston, TX; and San Antonio, TX; and from Liberty University,
      Lynchburg, Virginia. The sample was randomly split in two. In the first half (n =
      214), exploratory factor analysis identified the highest loading item on each of
      the 10 MISS scales (guilt, shame, moral concerns, loss of meaning, difficulty
      forgiving, loss of trust, self-condemnation, religious struggle, and loss of
      religious faith) to form the 10-item MISS-M-SF; confirmatory factor analysis was
      then performed to replicate results in the second half of the sample (n = 213).
      Internal reliability, test-retest reliability, and convergent, discriminant, and
      concurrent validity were examined in the overall sample. The study was approved
      by the institutional review boards and the Research & Development (R&D)
      Committees at Veterans Administration medical centers in Durham, Los Angeles,
      Augusta, Houston, and San Antonio, and the Liberty University and Duke University
      Medical Center institutional review boards. Findings: The 10-item MISS-M-SF had a
      median of 50 and a range of 12-91 (possible range 10-100). Over 70% scored a 9 or
      10 (highest possible) on at least one item. Cronbach's alpha was 0.73 (95% CI
      0.69-0.76), and test-retest reliability was 0.87 (95% CI 0.79-0.92). Convergent
      validity with the 45-item MISS-M was r = 0.92. Discriminant validity was
      demonstrated by relatively weak correlations with social, religious, and physical
      health constructs (r = 0.21-0.35), and concurrent validity was indicated by
      strong correlations with PTSD, depression, and anxiety symptoms (r = 0.54-0.58).
      Discussion: The MISS-M-SF is a reliable and valid measure of MI symptoms that can
      be used to screen for MI and monitor response to treatment in veterans and active
      duty military with PTSD.

PMID- 29590382
TI  - The impact of hot food takeaways near schools in the UK on childhood obesity: a
      systematic review of the evidence.
AB  - Background: Obesity is the greatest health issue for this generation; schools
      have improved food offered within their grounds. The built environment
      surrounding schools and pupils' journeys home have not received the same level of
      attention. This review identified papers on impacts of hot food takeaways
      surrounding schools in the UK. Methods: Methods were informed by the PRISMA
      (QUORUM) guidelines for systematic reviews. Searches were completed in 12
      databases. Results: A total of 14 papers were included and quality assured before
      data extraction. Three descriptive themes were found; descriptions of hot food
      takeaway's geography and impacts concerning schools, strategic food policy and
      pupils reported food behaviour. Conclusions: Most included studies compared
      anthropometric measures with geographical location of hot food takeaways to find
      correlations between environment and childhood obesity. There was good evidence
      of more hot food takeaways in deprived areas and children who spend time in
      deprived neighbourhoods tend to eat more fast food and have higher BMIs. Few
      studies were able to quantify the correlation between school's environment and
      obesity amongst pupils. This lack of evidence is likely a factor of the studies'
      ability to identify the correlation rather than lack of a correlation between the
      two variables.

PMID- 29590381
TI  - The Circadian Rhythm-Related MTNR1B Genotype, Gestational Weight Gain, and
      Postpartum Glycemic Changes.
AB  - Context: Disturbed circadian rhythms and sleep quality during pregnancy have been
      related to gestational weight gain and gestational diabetes mellitus (GDM), which
      affect postpartum glucose metabolism and future risk of type 2 diabetes.
      Objective: We assessed whether the circadian rhythm-related melatonin receptor 1B
      (MTNR1B) genotype was associated with 1 to 5 years of postpartum glycemic changes
      among women with a history of GDM and whether gestational weight gain modified
      such associations. Design, Settings, and Participants: The established circadian
      rhythm-associated MTNR1B genetic variant (rs10830963) was genotyped in 1025
      Chinese women with a history of GDM. Body weight and glycemic traits, during and
      after pregnancy, were longitudinally collected. Main Outcome Measures: The main
      outcome measure was postpartum glycemic changes. Results: We found that women
      carrying different MTNR1B genotypes showed distinct postpartum changes in 2-hour
      oral glucose tolerance test: 0.36, 0.20, and -0.19 mM per additional copy of the
      shorter sleep duration-related G allele in women with inadequate, adequate, and
      excessive gestational weight gain, respectively (for interaction, P = 0.028). The
      corresponding changes in fasting glucose were 0.14, 0.13, and 0.01 mM, although
      the modification effect of gestational weight gain on the genetic association was
      marginally significant (for interaction, P = 0.067). Conclusions: Our findings
      suggest that gestational weight gain may modify the circadian rhythm-related
      MTNR1B genetic variant on long-term glycemic changes, highlighting the
      significance of gestational weight management in diabetes prevention among women
      with GDM.

PMID- 29590383
TI  - The Cox-maze IV procedure in its second decade: still the gold standard?
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia and the treatment
      options include medical treatment and catheter-based or surgical interventions.
      AF is a major cause of stroke, and its prevalence is increasing. The surgical
      treatment of AF has been revolutionized over the past 2 decades through surgical
      innovation and improvements in endoscopic imaging, ablation technology and
      surgical instrumentation. The Cox-maze (CM) procedure, which was developed by
      James Cox and introduced clinically in 1987, is a procedure in which multiple
      incisions are created in both the left and the right atria to eliminate AF while
      allowing the sinus impulse to reach the atrioventricular node. This procedure
      became the gold standard for the surgical treatment of AF. Its latest iteration
      is termed the CM IV and was introduced in 2002. The CM IV replaced the previous
      cut-and-sew method (CM III) by replacing most of the incisions with a combination
      of bipolar radiofrequency and cryoablation. The use of ablation technologies,
      made the CM IV technically easier, faster and more amenable to minimally invasive
      approaches. The aims of this article are to review the indications and
      preoperative planning for the CM IV, to describe the operative technique and to
      review the literature including comparisons of the CM IV with the previous cut
      and-sew method. Finally, this review explores future directions for the surgical
      treatment of patients with AF.

PMID- 29590384
TI  - Atrial remodelling and function: implications for atrial fibrillation surgery.
AB  - The exact mechanism of atrial fibrillation (AF) is still incompletely understood.
      A number of alterations that impact focal electrical discharge, the atrial
      substrate and modulating factors contribute to its pathogenesis. Atrial
      remodelling (resulting in atrial cardiomyopathy) sets the stage for AF
      development. Once present, AF results in the loss of synchronized atrial
      contraction, which affects ventricular filling and atrial reservoir and conduit
      functions. Passive atrial function is particularly important in patients with
      left ventricular diastolic dysfunction. AF can cause tachycardiomyopathy, a
      mostly reversible cardiac alteration induced by tachycardia. At a structural
      level, atrial support is also instrumental to the function of atrioventricular
      valves. All of these functions can be recovered to variable degrees via rhythm
      control strategies. Surgical and hybrid ablation show very promising results,
      especially in patients with a more advanced disease substrate. This review
      highlights the pathophysiological aspects of AF related to left atrial function
      and their practical implications for surgical rhythm management.

PMID- 29590385
TI  - The New 2016 European Society of Cardiology/European Association for Cardio
      Thoracic Surgery Guidelines: Enough Guidance? Enough Evidence?
AB  - For the first time, the European Society of Cardiology and the European
      Association for Cardio-Thoracic Surgery have joined forces to develop consensus
      guidelines for the management of atrial fibrillation (AF). One of the main issues
      is the integrated care of patients with AF, with emphasis on multidisciplinary
      teams of general physicians, cardiologists, stroke specialists and surgeons,
      together with the patient's involvement for better management of AF. These
      guidelines also help in the detection of risk factors and concomitant
      cardiovascular diseases, stroke prevention therapies, including anticoagulation
      and antiplatelet therapies after acute coronary episodes, major haemorrhages or
      strokes. In the field of ablation, surgery plays an important role as concomitant
      with other surgical procedures, and it should be considered in symptomatic
      patients with the highest level of evidence. Asymptomatic patients with mitral
      insufficiency should also be considered for combined mitral and AF surgery if
      they have new-onset AF. In patients with stand-alone AF, recommendations for
      minimally invasive ablation have an increased level of recommendation and should
      be considered as the same level as catheter ablation in patients with persistent
      or long-standing persistent AF or with paroxysmal AF who fail catheter ablation.
      Surgical occlusion or exclusion of the left atrial appendage may be considered
      for stroke prevention in patients with AF about to have surgery. Nevertheless,
      not enough is known to avoid long-term anticoagulation in patients at risk of
      stroke even if the left atrial appendage has been excluded. These Guidelines
      provide a full spectrum of recommendations on the management of patients with AF
      including prevention, treatment and complications based on the latest published
      evidence.

PMID- 29590386
TI  - Surgical management of the left atrial appendage: a must or a myth?
AB  - Surgical treatment of the left atrial appendage (LAA) has increased over the past
      few years. The most serious complication of atrial fibrillation is a cerebral
      cardioembolic stroke. In most patients with atrial fibrillation, the LAA is the
      anatomical source of the embolism. Several surgical techniques for occluding the
      LAA using different devices have been developed with different prospects of
      success. It is still not clear which of these techniques represents the optimum
      treatment for reducing the incidence of stroke in patients with atrial
      fibrillation. This text focuses on the surgical closure of LAA and critically
      considers the results with respect to closure success and the associated
      complications.

PMID- 29590387
TI  - Three-year follow-up of hybrid ablation for atrial fibrillation.
AB  - OBJECTIVES: The single-step hybrid atrial fibrillation (AF) ablation procedure
      combines a transvenous endocardial and thoracoscopic epicardial approach in 1
      procedure. Short-term results are encouraging, but long-term outcome data are not
      available. METHODS: Hybrid AF ablation was successfully performed in 64
      consecutive patients (53% with persistent AF). The mean follow-up period was 1732
      +/- 353 days. Perprocedural endocardial touch-up of incomplete epicardial lesions
      was performed in 17 (26%) patients. RESULTS: In paroxysmal AF patients,
      arrhythmia-free cumulative survival rates after 1 hybrid AF ablation without
      Class I or III antiarrhythmic drugs procedure and without redo catheter ablation
      were 83%, 80% and 80% after 1, 2 and 3 years, respectively. In (long-standing)
      persistent AF patients, these were 82%, 79% and 79% after 1, 2 and 3 years.
      Thirteen (20%) patients had at least 1 recurrent episode of supraventricular
      arrhythmia lasting longer than 30 s: the most frequent recurrent arrhythmias were
      left atrial flutter and AF. No mortality or conversion to cardiopulmonary bypass,
      no phrenic nerve palsy and no pacemaker implantation were reported. CONCLUSIONS:
      Hybrid AF ablation, combining a transvenous endocardial and thoracoscopic
      epicardial approach in a single procedure, results in a cumulative 3-year freedom
      from arrhythmia without Class I or III antiarrhythmic drugs and without redo
      catheter ablation of 80% in paroxysmal AF (24 of 30 patients) and 79% in non
      paroxysmal AF (26 of 33 patients).

PMID- 29590388
TI  - FRET-ting about RhoA signalling in heart and vasculature: a new tool in our
      cardiovascular toolbox.

PMID- 29590389
TI  - Katie Thomas talks to Rory Collins, international leader in population and
      epidemiology studies in cardiovascular disease.

PMID- 29590390
TI  - Why we should reward peer reviewers.

PMID- 29590391
TI  - Reperfusion in the brain: is time important? The DAWN and DEFUSE-3 trials.

PMID- 29590392
TI  - Editorial: Special issue on anaerobic biological dehalogenation.

PMID- 29590393
TI  - Long non-coding RNA expression profiles reveals AK098783 is a biomarker to
      predict poor prognosis in patients with colorectal cancer.
AB  - Background: Long non-coding RNAs (lncRNAs) have essential regulatory function,
      yet their roles in colorectal cancer (CRC) are not well understood. Materials and
      methods: Microarray was applied to detect lncRNAs expression profiles in tumor
      tissues, liver metastasis and paired adjacent normal tissues of CRC. And using RT
      PCR to verify chip results. Results: A total of 10 680 lncRNAs demonstrated
      differential expressions (fold change >=2) between tumor tissues and adjacent
      normal tissues; furthermore there were 2970 lncRNAs, which showed different
      expression level between CRC tissues with liver metastasis and adjacent normal
      tissues. Especially, lncRNA-AK098783 expression level was frequently higher in
      cancerous tissues than corresponding noncancerous tissue. Higher AK098783
      expression was significantly correlated with shortened overall survival (P <
      0.001) and distant metastasis (P < 0.001). Conclusions: Our results suggest that
      AK098783 is involved in distant metastasis and dramatically associated with poor
      prognosis in patients with CRC.

PMID- 29590394
TI  - Evolutionary Origins of Toll-like Receptor Signaling.
AB  - Toll-like receptors (TLRs) are transmembrane pattern recognition receptors that
      are best known for their roles in innate immunity for the detection of and
      defense against microbial pathogens. However, TLRs also have roles in many
      nonimmune processes, most notably development. TLRs direct both immune and
      developmental programs by activation of downstream signaling pathways, often by
      activation of the NF-kappaB pathway. There are two primary TLR subtypes: 1) TLRs
      with multiple cysteine clusters in their ectodomain (mccTLRs) and 2) TLRs with a
      single cysteine cluster in their ectodomain (sccTLRs). For some time, it has been
      known that TLRs and the biological processes that they control are conserved in
      organisms from insects to mammals. However, genome and transcriptome sequencing
      has revealed that many basal metazoans also have TLRs and downstream NF-kappaB
      signaling components. In this review, we discuss what is known about the
      structure, biological function, and downstream signaling pathways of TLRs found
      in phyla from Porifera through Annelida. From these analyses, we hypothesize that
      mccTLRs emerged in the phylum Cnidaria, that sccTLRs evolved in the phylum
      Mollusca, and that TLRs have dual immune and developmental biological functions
      in organisms as ancient as cnidarians.

PMID- 29590395
TI  - Anaerobic phototrophic processes of hydrogen production by different strains of
      microalgae Chlamydomonas sp.
AB  - Hydrogen is an abundant element and a non-polluting fuel that can be biologically
      produced by microalgae. The aim of this research was to investigate biological
      hydrogen production by Chlamydomonas reinhardtii (CC425) and Chlamydomonas
      moewusii (SAG 24.91) by direct biophotolysis in batch cultures. Strains were
      cultivated in TAP growth medium (pH 7.2) in two phases: in the first stage,
      cultures were maintained in an aerobic condition until the middle of the
      exponential phase; in the second stage, the biomass was transferred to closed
      anaerobic photobioreactors under sulfur deprived. Gas chromatography and Gompertz
      model were used to measure the hydrogen production and hydrogen production rate,
      respectively. We noticed that maximum hydrogen production by biomass of C.
      reinhardtii was 5.95 +/- 0.88 MUmol mg-1 and the productivity was 17.02 +/- 3.83
      MUmol L-1 h-1, with hydrogen production five times higher than C. moewusii,
      approximately, though, C. moewusii obtained a higher ethanol yield compared to C.
      reinhardtii. The hydrogen production method, with the cultivation of strains in
      two different phases and sulfur deprivation, was effective for obtaining of
      biohydrogen for Chlamydomonas; however, it depends on the species, strain and
      growth conditions.

PMID- 29590396
TI  - The Genus Dermacentor (Acari: Ixodidae) in Laos: A Review and Update of Species
      Records.
AB  - Two species of the ixodid tick genus Dermacentor Koch, 1844 (Acari: Ixodidae)
      have previously been documented from Laos: D. auratus Supino, 1897 and D. steini
      (Schulze, 1933). Between 2012 and 2017, we recorded four additional Dermacentor
      species from this country: D. bellulus (Schulze, 1935); D. compactus Neumann,
      1901; D. filippovae Apanaskevich & Apanaskevich, 2015; and D.
      tamokensisApanaskevich & Apanaskevich, 2016. In addition, seven specimens in the
      tick collection at the Institut Pasteur du Laos may represent new species and are
      currently under taxonomic investigation.

PMID- 29590397
TI  - An Ecoinformatics Approach to Field-Scale Evaluation of Insecticide Effects in
      California Citrus: Are Citrus Thrips and Citrus Red Mite Induced Pests?
AB  - Experimental approaches to studying the consequences of pesticide use, including
      impacts on beneficial insects, are vital; however, they can be limited in scale
      and realism. We show that an ecoinformatics approach that leverages existing data
      on pesticides, pests, and beneficials across multiple fields can provide
      complementary insights. We do this using a multi-year dataset (2002-2013) on
      pesticide applications and density estimates of two pests, citrus thrips
      (Scirtothrips citri (Moulton [Thysanoptera: Thripidae])) and citrus red mites
      (Panonychus citri McGregor [Acari: Tetranychidae]), and a natural enemy (Euseius
      spp. predatory mites) collected from citrus groves in the San Joaquin Valley of
      California. Using correlative analyses, we investigated the long-term
      consequences of pesticide use on S. citri and P. citri population densities to
      evaluate the hypothesis that the pest status of these species is largely due to
      the disruption of natural biological control-i.e., these are induced pests. We
      also evaluated short-term pesticide efficacy (suppression of citrus thrips and
      citrus red mite populations immediately post-application) and asked if it was
      correlated with the suppression of Euseius predator populations. Although the
      short-term efficacy of different pesticides varied significantly, our dataset
      does not suggest that the use of citrus pesticides suppressed Euseius densities
      or worsened pest problems. We also find that there is no general trade-off
      between pesticide efficacy and pesticide risk to Eusieus, such that highly
      effective and minimally disruptive compounds were available to citrus growers
      during the studied time period.

PMID- 29590398
TI  - General practitioners' use of sickness certification guidelines in Sweden at
      introduction and four years later: a survey study.
AB  - Objective: National sickness certification guidelines were introduced in Sweden
      in 2007, comprising both overarching and diagnoses-specific recommendations. This
      study aimed to investigate how general practitioners (GP) used and perceived the
      usefulness of these guidelines in the sickness certification process close after
      introduction and 4 years later. Design: Two nationwide cross-sectional surveys in
      2008 and 2012. Setting: Swedish healthcare. Participants: Physicians working in
      primary healthcare and having sickness certification consultations at least a few
      times per year (n = 4214 in 2008, and n = 4067 in 2012). Main Outcome Measures:
      Frequency of use and perceived usefulness of the sickness certification
      guidelines. Results: Most GPs used the guidelines at least a few times per year
      (in 2008 74.6%; in 2012 85.2%). In 2008, 44.1% reported a need to develop
      competence in using the guidelines, compared with 23.3% in 2012. Of those using
      the guidelines, 36.7% in 2008 and 44.6% in 2012 reported it problematic to write
      sickness certificates in accordance with the guidelines. Most GPs (89.2% in 2008
      and 88.8% in 2012) valued the guidelines beneficial to ensure quality in sickness
      certification consultations. A larger proportion in 2012 compared with 2008
      reported that the guidelines facilitated contacts with patients (61.2%,
      respectively, 55.6%), as well as with other stakeholders. Conclusions: The
      guidelines were perceived as useful and beneficial to ensure high quality in
      sickness certification consultations, and facilitated contacts with patients as
      well as other stakeholders. In 2012, still one-fourth reported a need to develop
      more competence in using the sickness certification guidelines.

PMID- 29590399
TI  - Patterns of cancer treatment in different age groups in Japan: an analysis of
      hospital-based cancer registry data, 2012-2015.
AB  - Background: Because of the physiological decline and the diversity of
      preferences, treating older patients with cancer is challenging. Given the
      insufficient evidence applicable to treating cancer in older patients, some
      clinical guidance is necessary. This study provides a description of current
      treatment practices in Japan, which may shed light on possible treatment options.
      Methods: Using data from the national database of hospital-based cancer
      registries, we described the first-course treatment of nine common cancers in
      patients who received care in Designated Cancer Care Hospitals between 2012 and
      2015. We compared the patterns of first-course cancer treatment between younger
      and older patients. Results: In total, 1 383 066 cases were analysed. The
      proportion of patients aged >75 years receiving first-course treatment has
      gradually increased since 2012 (range: 0.9% point increase for colorectal cancer
      to 2.7% point increase for stomach cancer). A higher proportion of patients aged
      >=85 years, compared with younger patients, did not receive any treatment.
      Conclusions: Based on this cancer registry-based analysis, older patients-in
      particular those >=85 years old at diagnosis and with advanced stage cancer-are
      less likely to receive anti-cancer treatment than younger patents are. Further
      research is warranted to identify patient characteristics that predict which
      older patients are most likely to benefit from active treatment.

PMID- 29590400
TI  - Perceptions and attitudes regarding antibiotic resistance in Germany: a cross
      sectoral survey amongst physicians, veterinarians, farmers and the general
      public.
AB  - Background: Drivers of antibiotic (AB) resistance (ABR) include outpatient
      treatment, hospital care and animal husbandry. During the first phase of the One
      Health project RAI (Responsible Antibiotic Use via Information and Communication)
      surveys were conducted in these sectors. Objectives: To compare perceptions and
      attitudes towards ABR among general practitioners (GPs), hospital physicians,
      veterinarians, pig farmers and the general public. Methods: Cross-sectional
      questions on AB use and ABR were integrated in group-specific surveys of GPs,
      hospital physicians, veterinarians, pig farmers and the German general
      population. Results: A total of 1789 participants (340 GPs, 170 hospital
      physicians, 215 pig farmers, 60 veterinarians and 1004 members of the public)
      responded. Each group tended to identify drivers of ABR as being from outside its
      own area of activity. Guidelines were shown to be an important information source
      for AB therapy for all prescriber groups, but the frequency of routine use
      differed (39% of GPs, 65% of hospital physicians and 53% of veterinarians).
      Regarding further information sources, hospital physicians preferred smartphone
      apps and e-learning, GPs preferred non-sponsored training and veterinarians
      preferred multidisciplinary networks and e-learning. Farmers were predominantly
      satisfied with existing solutions. Farmers had three times better basic knowledge
      of ABR and knew twice as many people with MDR organism problems than the general
      public. They also received information on ABR more often from their veterinarians
      than patients did from their doctors. Conclusions: This study reveals
      considerable differences in perceptions and attitudes to ABR among the groups
      investigated. The results can help to tailor future interventions. Furthermore,
      they promote mutual understanding and thus support the One Health approach.

PMID- 29590401
TI  - Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense
      Against Hypoglycemia.
AB  - Context: Hypoglycemia, one of the major factors limiting optimal glycemic control
      in insulin-treated patients with diabetes, elicits a brain response to restore
      normoglycemia by activating counterregulation. Animal data indicate that local
      release of norepinephrine (NE) in the hypothalamus is important for triggering
      hypoglycemia-induced counterregulatory (CR) hormonal responses. Objective: To
      examine the potential role of brain noradrenergic (NA) activation in humans
      during hypoglycemia. Design: A hyperinsulinemic-hypoglycemic clamp was performed
      in conjunction with positron emission tomographic imaging. Participants: Nine
      lean healthy volunteers were studied during the hyperinsulinemic-hypoglycemic
      clamp. Design: Participants received intravenous injections of (S,S)-[11C]O
      methylreboxetine ([11C]MRB), a highly selective NE transporter (NET) ligand, at
      baseline and during hypoglycemia. Results: Hypoglycemia increased plasma
      epinephrine, glucagon, cortisol, and growth hormone and decreased [11C]MRB
      binding potential (BPND) by 24% +/- 12% in the raphe nucleus (P < 0.01). In
      contrast, changes in [11C]MRB BPND in the hypothalamus positively correlated with
      increments in epinephrine and glucagon levels and negatively correlated with
      glucose infusion rate (all P < 0.05). Furthermore, in rat hypothalamus studies,
      hypoglycemia induced NET translocation from the cytosol to the plasma membrane.
      Conclusions: Insulin-induced hypoglycemia initiated a complex brain NA response
      in humans. Raphe nuclei, a region involved in regulating autonomic output, motor
      activity, and hunger, had increased NA activity, whereas the hypothalamus showed
      a NET-binding pattern that was associated with the individual's CR response
      magnitude. These findings suggest that NA output most likely is important for
      modulating brain responses to hypoglycemia in humans.

PMID- 29590402
TI  - Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.
AB  - Context: Thyroid nodules, adenomas, and goiter have consistently been associated
      with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction
      and thyroid autoimmunity influence this risk. Objective: To examine thyroid
      cancer risk after diagnoses of a wide range of benign thyroid conditions. Design:
      Hospital and cancer registry linkage cohort study for the years 1978 to 2013.
      Setting: Nationwide (Denmark). Participants: Patients diagnosed with
      hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n =
      12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582),
      other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807
      residents of Denmark during the study period. Main Outcome Measures: We computed
      standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding
      the first 12 months of follow-up after benign thyroid disease diagnosis. Results:
      SIRs were significantly elevated for all benign thyroid diseases apart from
      hypothyroidism. SIRs were higher for men than women and in the earlier follow-up
      periods. Elevated SIRs were observed for localized and regional/distant thyroid
      cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27
      thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92],
      nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter
      (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR
      = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to
      11.5) remained positively associated with thyroid cancer risk. Conclusions: We
      found an unexpected increased risk of differentiated thyroid cancer, including
      regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis
      that could not be solely attributed to increased medical surveillance.
      Hypothyroidism was less clearly associated with thyroid cancer risk.

PMID- 29590403
TI  - p.Val804Met, the Most Frequent Pathogenic Mutation in RET, Confers a Very Low
      Lifetime Risk of Medullary Thyroid Cancer.
AB  - Context: To date, penetrance figures for medullary thyroid cancer (MTC) for
      variants in rearranged during transfection (RET) have been estimated from
      families ascertained because of the presence of MTC. Objective: To gain estimates
      of penetrance, unbiased by ascertainment, we analyzed 61 RET mutations assigned
      as disease causing by the American Thyroid Association (ATA) in population whole
      exome sequencing data. Design: For the 61 RET mutations, we used analyses of the
      observed allele frequencies in ~51,000 individuals from the Exome Aggregation
      Consortium (ExAC) database that were not contributed via The Cancer Genome Atlas
      (TCGA; non-TCGA ExAC), assuming lifetime penetrance for MTC of 90%, 50%, and
      unbounded. Setting: Population-based. Results: Ten of 61 ATA disease-causing RET
      mutations were present in the non-TCGA ExAC population with observed frequency
      consistent with penetrance for MTC of >90%. For p.Val804Met, the lifetime
      penetrance for MTC, estimated from the allele frequency observed, was 4% [95%
      confidence interval (CI), 0.9% to 8%]. Conclusions: Based on penetrance analysis
      in carrier relatives of p.Val804Met-positive cases of MTC, p.Val804Met is
      currently understood to have high-lifetime penetrance for MTC (87% by age 70),
      albeit of later onset of MTC than other RET mutations. Given our unbiased
      estimate of penetrance for RET p.Val804Met of 4% (95% CI, 0.9% to 8%), the
      current recommendation by the ATA of prophylactic thyroidectomy as standard for
      all RET mutation carriers is likely inappropriate.

PMID- 29590404
TI  - Intraoperative customized double-patch device with twin sutures for multiple
      muscular septal defects.
AB  - OBJECTIVES: Closure of multiple muscular ventricular septal defects (VSDs)
      remains a challenge because of anatomical complexity. METHODS: We mapped all the
      VSDs using en face reconstruction of the right ventricular septal surface through
      echocardiography and then performed an 'Intraoperative Customized Double-Patch
      Device' technique to surgically close them in 39 patients (male:female = 25:14).
      The median age of the patients was 6 months (2 months-10 years), and mean weight
      was 5.98 +/- 4.21 kg. A patch of polytetrafluoroethylene was placed on the left
      ventricular side of the defect and another on the right ventricular side, and
      they were anchored to each other using 2 polypropylene sutures. Residual shunts
      were evaluated using intraoperative echocardiography and measurements of right
      atrial-pulmonary arterial saturation were taken in all patients. RESULTS: The
      distribution of muscular VSDs was as follows: anterior muscular 12, posterior
      muscular 18, mid-muscular 11 and apical 9. The associated lesions included
      perimembranous VSD (n = 28), tetralogy of Fallot (n = 6), double-outlet right
      ventricle (n = 2) and supramitral membrane (n = 2). Mean clamp time and bypass
      time were 93 +/- 19 min and 147 +/- 26 min, respectively. Mean hospital stay was
      11 +/- 3.39 days with no in-hospital mortality. Five patients with significant
      residual shunts needed concomitant PA banding. All patients remained in New York
      Heart Association Class I. There was either no residual shunt (n = 3) or trivial
      shunt (n = 2) among the banded patients. All patients remained symptom-free and
      continued to thrive well at the most recent follow-up (3.48 +/- 1.51 years).
      CONCLUSIONS: Muscular VSDs can be mapped through en face reconstruction and
      closed using intraoperative customized double-patch device technique in a variety
      of situations with satisfactory immediate and short-term results.

PMID- 29590405
TI  - Selection of host-plant genotype: the next step to increase grain legume N2
      fixation activity.
AB  - Symbiotic N2 fixation research thus far has been primarily focused on selection
      of bacteria. However, little progress in impacting crop yields has resulted from
      this approach. Bacteria introduced in field soils rarely compete well with
      indigenous bacteria, including mutated lines selected for high nitrogen fixation
      capacity. Consequently, introduction of 'elite' bacteria in fields commonly does
      not result in crop yield increase. This review highlights that the primary
      regulation of N2 fixation is a result of response of integrated physiological
      activity at the plant level. Nitrogen feedback from the host plant plays an
      important role in regulating the N2 fixation rate. Rapid sequestration of fixed
      nitrogen by the plant is especially important for high N2 fixation activity. In
      addition, water cycling in the plant between the shoot and nodules plays a key
      role in sustaining high N2 fixation activity. Therefore, attention in selecting
      the host-plant genotype is suggested to be the next step to increasing N2
      fixation activity of grain legumes.

PMID- 29590406
TI  - Medical Evaluation Board Involvement, Non-Credible Cognitive Testing, and
      Emotional Response Bias in Concussed Service Members.
AB  - Introduction: Military Service Members (SMs) with post-concussive symptoms are
      commonly referred for further evaluation and possible treatment to Department of
      Defense Traumatic Brain Injury Clinics where neuropsychological
      screening/evaluations are being conducted. Understudied to date, the base rates
      of noncredible task engagement/performance validity testing (PVT) during
      cognitive screening/evaluations in military settings appears to be high. The
      current study objectives are to: (1) examine the base rates of noncredible PVTs
      of SMs undergoing routine clinical or Medical Evaluation Board (MEB) related
      workups using multiple objective performance-based indicators; (2) determine
      whether involvement in MEB is associated with PVT or symptom exaggeration/symptom
      validity testing (SVT) results; (3) elucidate which psychiatric symptoms are
      associated with noncredible PVT performances; and (4) determine whether MEB
      participation moderates the relationship between psychological symptom
      exaggeration and whether or not SM goes on to demonstrate PVTs failures - or vice
      versa. Materials and Methods: Retrospective study of 71 consecutive military
      concussion cases drawn from a DoD TBI Clinic neuropsychology clinic database. As
      part of neuropsychological evaluations, patients completed several objective
      performance-based PVTs and SVT. Results: Mean (SD) age of SMs was 36.0 (9.5),
      ranging from 19-59, and 93% of the sample was male. The self-identified ethnicity
      resulted in the following percentages: 62% Non-Hispanic White, 22.5% African
      American, and 15.5% Hispanic or Latino. The majority of the sample (97%) was
      Active Duty Army and 51% were involved in the MEB at the time of evaluation.
      About one-third (35.9%) of routine clinical patients demonstrated failure on one
      or more PVT indicators (12.8% failed 2) while PVT failure rates amongst MEB
      patients ranged from 15.6% to 37.5% (i.e., failed 2 or 1 PVTs, respectively).
      Base rates of failures on one or more PVT did not differ between routine clinical
      versus MEB patients (p = 0.94). MEB involvement was not associated with increased
      emotional symptom response bias as compared to routine clinical patients. PVT
      failures were positively correlated with somatization, anxiety, depressive
      symptoms, suspicious and hostility, atypical perceptions/alienation/subjective
      cognitive difficulties, borderline personality traits/features, and penchant for
      aggression in addition to symptom over-endorsement/exaggeration. No differences
      between routine clinical and MEB patients across other SVT indicators were found.
      MEB status did not moderate the relationship between any of the SVTs. Conclusion:
      Study results are broadly consistent with the prior published studies that
      documented low to moderately high base rates of noncredible task engagement
      during neuropsychological evaluations in military and veteran settings. Results
      are in contrast to prior studies that have suggested involvement in MEB is
      associated with increased likelihood of poor PVT performances. This is the first
      to show that MEB involvement did not enhance/strengthen the association between
      PVT performances and evidence of SVTs. Consistent with prior studies, these
      results do highlight that the same SMs who fail PVTs also tend to be the ones who
      go on to endorse a myriad of psychiatric symptoms and proclivities. Implications
      of variable or poor task engagement during routine clinical and MEB
      neuropsychological evaluation in military settings on treatment and disposition
      planning cannot be overstated.

PMID- 29590407
TI  - Costs associated with febrile neutropenia in Japanese patients with primary
      breast cancer: post-hoc analysis of a randomized clinical trial.
AB  - Background: Febrile neutropenia (FN), a decrease in blood neutrophils accompanied
      by fever, is a major adverse event (AE) associated with cancer chemotherapy. We
      aimed to estimate the direct medical costs associated with FN management in
      breast cancer patients within a clinical trial with pegfilgrastim, a pegylated
      form of recombinant granulocyte colony-stimulating factor (G-CSF). Methods: We
      obtained data from 346 Japanese breast cancer patients in a randomized, placebo
      controlled clinical trial comparing FN incidence due to TC adjuvant chemotherapy
      (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) between pegfilgrastim-treated
      and placebo groups. We estimated mean costs for chemotherapy drugs, drugs for all
      AEs and FN, and hospitalization for all AEs and FN. We also calculated mean costs
      associated with drugs and hospitalization for FN specifically for patients who
      developed FN in the placebo group. Results: For the pegfilgrastim and placebo
      groups, the total cost during the first cycle of chemotherapy was Y189 135 and
      Y98 106. This difference is associated with prophylactic use of pegfilgrastim.
      Our analysis clarified in the placebo group that FN incidents of 119/173 (68.6%),
      the mean drug cost related to all AEs and hospitalization caused by the first
      cycle of chemotherapy were Y14 411and Y11 180, respectively. The cost of each for
      FN treatment was Y16 429 for the placebo group. The mean treatment cost for
      patients who developed FN in placebo group, was Y11 145 for drugs and Y28 420 for
      drugs and hospitalization. Conclusions: Pegfilgrastim reduced the costs incurred
      for both drugs and hospitalization for AEs as well as FN, although the total
      medical cost during the chemotherapy increased. Our study constitutes baseline
      data for further health economic evaluations of pegfilgrastim.

PMID- 29590408
TI  - Phase retrieval using through-focus images in Lorentz transmission electron
      microscopy.
AB  - In this study, we report on phase retrieval by the maximum likelihood method with
      conjugate gradient method (CG-MAL) using through-focus images in Lorentz
      transmission electron microscopy (LTEM). The method was evaluated using 32
      simulated and experimentally obtained through-focus images of magnetic bubbles;
      these images were collected under a defocus range from approximately -3 mm to 3
      mm. Consequently, we obtained the magnetic domain structures of the magnetic
      bubbles in both the simulation and the LTEM experiment. Furthermore, the CG-MAL
      method showed better convergence behavior than other iterative phase retrieval
      methods. Therefore, the method can also be widely and effectively applied to the
      observation of magnetic domain structures other than magnetic bubbles when highly
      defocused through-focus images are used.

PMID- 29590409
TI  - Motor Unit Number Estimate and Isometric Hand Grip Strength in Military Veterans
      with or Without Muscular Complaints: Reference Values for Longitudinal Follow-up.
AB  - Introduction: It remains unclear if Gulf War (GW) veterans have a higher risk of
      developing motor neuron disorder. We intended to establish baseline
      neurophysiological values, including thenar motor unit number estimate (MUNE) and
      isometric hand grip (IHG) strength, to compare future follow-ups of deployed GW
      veterans with or without muscular complaints. Materials and Methods: We evaluated
      19 GW veterans with self-reported weakness, cramps, or excessive muscle fatigue
      (Ill-19) and compared them with 18 controls without such muscular complaints (C
      18). We performed MUNE on hand thenar muscles using adapted multipoint
      stimulation method for Ill-19 and 15 controls (C-15). We measured IHG strength
      (maximum force, endurance, and fatigue level) on Ill-19 and C-18 with a hand
      dynamometer. We performed nerve conduction studies on all study participants to
      determine which subjects had mild carpal tunnel syndrome (CTS). We compared the
      MUNE and IHG strength measures between Ill group and controls and between those
      with CTS and those without CTS. Results: We obtained thenar MUNE of Ill-19 (95%
      CI of mean: 143-215; mean age: 46 yr) and compared it with that of C-15 (95% CI
      of mean: 161-230; mean age: 45 yr), and 95% of CI of mean among IHG strength
      variables (maximum force: 324-381 Newton; endurance: 32-42 s; fatigue level: 24%
      33%) compared with C-18 (maximum force: 349-408 Newton; endurance: 35-46 s;
      fatigue level: 21%-27%). There was no significant difference in either MUNE or
      IHG strength between Ill-19 group and controls. The MUNE and IHG maximum forces
      were significantly lower in those with CTS compared with those without CTS. As a
      surrogate of mild CTS, the median versus ulnar distal sensory latency on nerve
      conduction study was only weakly associated with MUNE, maximum force, and fatigue
      level, respectively. Conclusion: To our knowledge, no published study on MUNE
      reference values of military veteran population has been available. The
      quantifiable values of both thenar MUNE and IHG strength of military veterans
      serve as baselines for our longitudinal follow-up of motor neuron function of
      deployed troops. These reference values are also useful for other laboratories to
      study veterans' motor system with or without mild CTS.

PMID- 29590410
TI  - Stated Pain Levels, Opioid Prescription Volume, and Chronic Opioid Use Among
      United States Army Soldiers.
AB  - Introduction: The use of opioids has increased drastically over the past few
      years and decades. As a result, concerns have mounted over serious outcomes
      associated with chronic opioid use (COU), including dependency and death. A
      greater understanding of the factors that are associated with COU will be
      critical if prescribers are to navigate potentially competing objectives to
      provide compassionate care, while reducing the overall opioid use problem. In
      this study, we study pain levels and opioid prescription volumes and their
      effects on the risk of COU. This study leveraged passive data sources that
      support automated decision support systems (DSSs) currently employed in a large
      military population. The models presented compute monthly, person-specific,
      adjusted probability of subsequent COT and could potentially provide critical
      decision support for clinicians engaged in pain management. Materials and
      Methods: The study population included all outpatient presentations at military
      medical facilities worldwide among active duty United States Army soldiers during
      July 2011 to September 2014 (17,664,006 encounters; population N = 552,193). We
      conducted a retrospective cohort study of this population and employed
      longitudinal data and a discrete time multivariable logistic regression model to
      compute COT probability scores. The contribution of pain scores and opioid
      prescription quantities to the probability of COT represented analytic foci.
      Results: There were 13,891 subjects (2.5%) who experienced incident COT during
      the observed time period. Statistically significant interactions between pain
      scores and prescription quantity were present, in addition to effects of multiple
      other control variables. Counts of monthly opioid prescriptions and maximum
      stated pain scores per month were each positively associated with COT. A wide
      range in individual COT risk scores was evident. The effect of prescription
      volume on the COT risk was larger than the effect of the pain score, and the
      combined effect of larger pain scores and increased prescription quantity was
      moderated by the interaction term. Conclusions: The results verified that passive
      data on the US Army can support a robust COT risk computation in this population.
      The individual, adjusted risk level requires statistical analyses to be fully
      understood. Because the same data sources drive current military DSSs, this work
      provides the potential basis for new, evidence-based decision support resources
      for military clinicians. The strong, independent impact of increasing opioid
      prescription counts on the COT risk reinforces the importance of exploring
      alternatives to opioids in pain management planning. It suggests that changing
      provider behavior through enhanced decision support could help reduce COT rates.

PMID- 29590411
TI  - Wartime Soft Tissue Coverage Techniques for the Deployed Surgeon.
AB  - Background: Since the start of the conflict in the Middle East in 2001, military
      orthopedic surgeons have faced complex orthopedic injuries including high-energy
      soft tissue wounds, traumatic amputations, and open fractures. Although
      orthopedic surgeons are well trained in the management of osseous injuries, the
      treatment of soft tissue injuries can be technically challenging and unfamiliar.
      Early washout, debridement of devitalized tissue, external fixation of bony
      injuries, and antibiotic therapy remain the foundation of early wound management.
      However, these unique extremity injuries have no standard plan of care, and
      definitive treatment options continue to evolve. The following report highlights
      the typical cases seen in the wartime setting and offers possible solutions for
      the associated soft tissue injuries. Methods: A single orthopedic surgeon at a
      Role 3 combat support hospital performed all cases in this series. This study is
      a report of the cases that the orthopedic surgeon encountered while deployed and
      the various techniques that can be used to manage the complex wounds seen in a
      deployed setting. Findings: Twelve patients were included in this report and the
      data are shown. Of the 12 patients, 6 were injured by an improvised explosive
      device (IED), 4 were injured by a high-velocity gunshot wound (HVGSW), 1 was
      injured by a gunshot wound (GSW), and 1 was injured in an auto versus pedestrian
      motor vehicle crash. The wound sizes ranged from 10 to 300 cm2. All patients
      required more than one irrigation and debridement before wound closure. There was
      a successful outcome in 11 of the 12 patients. The only patient without a known
      successful outcome was lost to follow up. Six patients were treated with split
      thickness skin graft (STSG) alone. Four patients were treated with STSG plus an
      additional means of coverage. One patient was treated with a random flap and one
      patient was treated with a full thickness skin graft. Integra was used in two of
      the patients. Each of the patients in whom integra was used had exposed bone and
      had a successful outcome with respect to tissue coverage. Discussion: This study
      details different soft tissue coverage techniques that must be learned and
      possibly employed by the deployed surgeon. Limitations of this study include its
      retrospective nature and the selected sampling of cases. At initial presentation,
      the management of war wounds secondary to high-velocity gunshot wounds and
      improvised explosive devices can be quite daunting. Adhering to firm surgical
      principles of thorough and meticulous debridement is the foundation of later soft
      tissue reconstructive options. Once the tissue is deemed clear of infection and
      contamination, there are myriad treatment options utilizing flaps, synthetic
      materials, and skin grafting. These are relatively straightforward techniques
      that the general orthopedic surgeon can utilize while deployed in a combat
      setting. In the end, it is critical for deployed surgeons to learn multiple
      techniques to provide definitive soft tissue coverage in a wartime theater.

PMID- 29590412
TI  - Screening Spirometry in Military Personnel Correlates Poorly with Exercise
      Tolerance and Asthma History.
AB  - BACKGROUND: Spirometry is an easy-to-perform test for evaluating pulmonary
      symptoms but has several limitations to include adequate test performance for
      valid results. Spirometry is not recommended to screen a general population for
      evidence of pulmonary disease unless symptoms are present or longitudinal
      screening is done for potential occupational exposures. METHODS: A single
      spirometry examination was performed on 900 active duty Army soldiers, ages 18-35
      yr, without documented respiratory disease. Abnormal studies were identified
      (obstructive, restrictive, mixed, and flow volume loop abnormalities) and
      compared with reported respiratory symptoms, smoking history, prior diagnosis of
      asthma, and failure of the Army physical fitness test 2-mile run using
      generalized linear modeling techniques. RESULTS: The cohort population had
      spirometry values comparable with published NHANES III reference values. Ninety
      eight subjects (10.9%) were identified with abnormal spirometry included 33
      obstructive, 44 restrictive, 3 mixed, and 18 isolated flow volume loop
      abnormalities. Historical features (smoking, exertional dyspnea, cough, asthma,
      or APFT failure) had no effect on the probability of an abnormal spirometry
      result (p = 0.56). Although APFT failure probability is strongly affected by
      exertional dyspnea (p = 0.00) and current smoking (p = 0.01), abnormal spirometry
      results did not have a statistically significant effect (p = 0.38). DISCUSSION:
      For potential screening of military personnel with spirometry to detect pulmonary
      disease, study findings identified a significant percentage with non-specific
      abnormalities requiring further evaluation. Spirometry may be indicated in those
      individuals with a history of asthma or active dyspnea symptoms. Spirometry as a
      screening tool is poorly (and often incorrectly) predictive for respiratory
      symptoms or decreased exercise tolerance in a military cohort. CONCLUSION:
      Spirometry should not be used to screen the military force for the presence of
      respiratory disorders. In those individuals with a history of asthma, in-depth
      testing should be performed to fully evaluate any non-specific findings
      identified during spirometry.

PMID- 29590413
TI  - Identifying barriers to HIV testing in hospital admissions to improve HIV
      testing.

PMID- 29590414
TI  - Implications of upfront charging for NHS care: a threat to health and human
      rights.

PMID- 29590415
TI  - In Reply: Surgical Decision Making From Image-Based Biophysical Modeling of
      Glioblastoma: Not Ready for Primetime.

PMID- 29590416
TI  - Opportunistic screening for alcohol use problems in adolescents attending
      emergency departments: an evaluation of screening tools.
AB  - Objective: To estimate and compare the optimal cut-off score of Alcohol Use
      Disorders Identification Test (AUDIT) and AUDIT-C in identifying at-risk alcohol
      consumption, heavy episodic alcohol use, ICD-10 alcohol abuse and alcohol
      dependence in adolescents attending ED in England. Design: Opportunistic cross
      sectional survey. Setting: 10 emergency departments across England. Participants:
      Adolescents (n = 5377) aged between their 10th and 18th birthday who attended
      emergency departments between December 2012 and May 2013. Measures: Scores on the
      AUDIT and AUDIT-C. At-risk alcohol consumption and monthly episodic alcohol
      consumption in the past 3 months were derived using the time-line follow back
      method. Alcohol abuse and alcohol dependence was assessed in accordance with ICD
      10 criteria using the MINI-KID. Findings: AUDIT-C with a score of 3 was more
      effective for at-risk alcohol use (AUC 0.81; sensitivity 87%, specificity 97%),
      heavy episodic use (0.84; 76%, 98%) and alcohol abuse (0.98; 91%, 90%). AUDIT
      with a score of 7 was more effective in identifying alcohol dependence (0.92;
      96%, 94%). Conclusions: The 3-item AUDIT-C is more effective than AUDIT in
      screening adolescents for at-risk alcohol use, heavy episodic alcohol use and
      alcohol abuse. AUDIT is more effective than AUDIT-C for the identification of
      alcohol dependence.

PMID- 29590417
TI  - Strategies for Establishing a Rearing Technique for the Fruit Fly Parasitoid:
      Doryctobracon brasiliensis (Hymenoptera: Braconidae).
AB  - Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) is the most important
      pest in South American orchards. When control measures are not adopted, this pest
      can cause losses of up to 100%. Doryctobracon brasiliensis (Szepligeti)
      (Hymenoptera: Braconidae) is a larval-pupal endoparasitoid that can be used as a
      native biological control agent against A. fraterculus. This study aimed to
      develop a rearing technique for D. brasiliensis in larvae of A. fraterculus.
      Trials were carried out to: 1) determine the optimal instar for parasitism, 2)
      define the exposure time of larvae to parasitoids, 3) determine the density
      requirements of A. fraterculus larvae offered to each parasitoid, and 4) evaluate
      the effect of diet on adults of D. brasiliensis. In all trials, we evaluated the
      number of offspring, parasitism rate, and sex ratio. Moreover, in the experiment
      to investigate the effects of diet, we determined the longevity of males and
      females. In both choice and nonchoice parasitism tests, the parasitoids preferred
      third-instar larvae of A. fraterculus over second- and first-instar larvae. An
      exposure time of 12 h of A. fraterculus larvae produced larger numbers of
      parasitoids and higher parasitism rates. The density of 15 larvae of A.
      fraterculus to each female of D. brasiliensis produced a larger number of
      offspring. A supply of honey solution (20 and 50%) to the parasitoids yielded the
      highest number offspring and resulted in greater longevity. Our findings can be
      used to support the development of a mass rearing protocol for D. brasiliensis.

PMID- 29590418
TI  - Transcriptional and post-translational regulation of AccD6 in Mycobacterium
      smegmatis.
AB  - AccD6 is an important component of acetyl-CoA/propionyl-CoA carboxylase, which
      acts as a key role in mycolic acid synthesis and short chain fatty acyl-coenzyme
      A metabolism. In this study, we demonstrated that AccD6 of Mycobacterium
      smegmatis associates with AccA3 (alpha subunit of acetyl-CoA carboxylase,
      MSMEG_1807) and AccE (epsilon subunit, MSMEG_1812) to form the acetyl-CoA
      (propionyl-CoA) carboxylase. Results showed that the MSMEG_4331 subunit is a
      regulator that interacts with the promoter region of accD6 to inhibit its
      transcription. Transcription of accD6 was reduced by 50% in the mutant M.
      smegmatis strain overexpressing MSMEG_4331. Moreover, the activity of AccD6 was
      inhibited by acylation (such as acetylation and propionylation). These results
      demonstrate that AccD6 of M. smegmatis is regulated at both the transcriptional
      and post-translational levels. Our findings highlight the novel regulatory
      mechanism underlying mycolic acid biosynthesis in mycobacteria.

PMID- 29590419
TI  - Combat Injury of the Sciatic Nerve - An Institutional Experience.
AB  - Introduction: Combat injury of the sciatic nerve tends to be severe with variable
      but often profound consequences, is often associated with widespread soft tissue
      and bone injuries, significant neurologic impairment, severe neuropathic pain,
      and a prolonged recovery time. There is little contemporary data that describes
      the treatment and outcome of this significant military acquired peripheral nerve
      injury. We describe our institution's experience treating patients with combat
      acquired sciatic nerve injury in the recent Iraq and Afghanistan wars. Materials
      and Methods: IRB approval was obtained, and a retrospective review was performed
      of the records of 5,137 combat-related extremity injuries between June 2007 and
      June 2015 to identify patients with combat-acquired sciatic nerve injury without
      traumatic amputation of the injured leg. The most common mechanisms of injury
      were gunshot wound to the upper thigh or pelvis, followed by blast injury.
      Thirteen patients were identified that underwent sciatic nerve exploration and
      repair. Nine patients had nerve repair using long-length acellular cadaveric
      allografts. Five patients underwent nerve surgery within 30 d of injury and eight
      had surgery on a delayed basis. The postoperative follow-up period was at least 2
      yr. Results: Reduction of neuropathic pain was significant, 7/10 points on the 11
      point pain intensity numerical rating scale. Eight patients displayed
      electrodiagnostic evidence of reinnervation distal to the injury zone; however,
      functional recovery was poor, as only 3 of 10 patients had detectable motor units
      distal to the knee, and recovery was only in tibial nerve innervated muscles.
      There were no serious surgical complications, in particular, wound infection or
      graft rejection associated with long-length cadaver allograft placement.
      Conclusion: Early surgery to repair sciatic nerve injury possibly promotes
      significant pain reduction, reduces narcotic usage and facilitates a long
      rehabilitation process. Allograft nerve placement is not associated with serious
      complications. A follow-up period longer than 3 yr would be required and is
      ongoing to assess the efficacy of our treatment of patients with combat-acquired
      sciatic nerve injury.

PMID- 29590420
TI  - On-pump transapical cardioscopic mitral valve replacement with cardiac arrest:
      short-term results in a porcine survival model.
AB  - OBJECTIVES: Favourable outcomes with mitral annuloplasty have been achieved with
      transapical cardioscopic (TAC) surgery in a survival animal model. In addition,
      experimental TAC on a non-survival animal model also showed adequate access to
      remove the native mitral valve and implant a prosthetic valve, but the surgical
      procedure took a long time and lacked follow-up data. The goal of this study was
      to develop a clinically translatable TAC mitral valve replacement (MVR) procedure
      using technical and instrumental refinements to reduce the surgical time and to
      evaluate functional recovery and short-term durability using a survival porcine
      model. We hypothesized that MVR could be achieved with subannular implantation of
      the bioprosthesis via the TAC approach. METHODS: TAC MVR using the Hancock IITM
      (Medtronic)(r) mitral prosthesis was performed in 6 pigs via an incision over the
      xiphoid process, under cardiopulmonary bypass and cardiac arrest. COR-KNOT(r) and
      minimally invasive cardiac surgery instruments were used. Haemodynamics,
      echocardiography, cardiac computed tomography, ventriculography and
      electrocardiography were used to evaluate the function of the mitral prosthesis
      and left ventricle, coronary system and conduction system in the perioperative
      period and 4 weeks later. RESULTS: A postimplant examination showed that the
      mitral prosthesis was competent, without a paravalvular leak. The left
      ventricular ejection fraction was comparable to preoperative values (65.2 +/- 4.1
      vs 67.2 +/- 7.9). The bypass, cross-clamp and implant times were 177.2 +/- 44.2
      min, 135.3 +/- 47.6 min and 94.0 +/- 41.2 min, respectively. The prosthesis was
      in a good position. The apical scar was intact and not aneurysmal 4 weeks after
      the implant. The valve was properly sutured to the annulus, without a postimplant
      paravalvular leak. All animals recovered after 1 month of follow-up with
      preserved ventricular function and normal wall motion. CONCLUSIONS: We
      successfully managed to replace the mitral valve with a biological prosthesis via
      the apex with encouraging bypass and cross-clamp times. This technique may
      provide an alternative for a selected group of patients with diseased mitral
      valves who have indications for MVR and still in a high-risk redo setting with
      conventional sternotomy or minimally invasive cardiac surgery-MVR.

PMID- 29590421
TI  - Incidence of Hypoglycemia After Gastric Bypass vs Sleeve Gastrectomy: A
      Randomized Trial.
AB  - Context: We compared the incidence of hypoglycemia after Roux-en-Y gastric bypass
      (RYGB) vs sleeve gastrectomy (SG). Design, Setting, and Main Outcome Measures:
      Randomized, open-label trial conducted at the outpatient obesity clinic in a
      university hospital in Rome, Italy. The primary aim was the incidence of reactive
      hypoglycemia (<3.1 mmol/L after 75-g oral glucose load) at 1 year after surgery.
      Secondary aims were hypoglycemia under everyday life conditions, insulin
      sensitivity, insulin secretion, and lipid profile. Results: Of 175 eligible
      patients, 120 were randomized 1:1 to RYGB or SG; 117 (93%) completed the 12-month
      follow-up. Reactive hypoglycemia was detected in 14% and 29% of SG and RYGB
      patients (P = 0.079), respectively, with the effect of treatment in multivariate
      analysis significant at P = 0.018. Daily hypoglycemic episodes during continuous
      glucose monitoring did not differ between groups (P = 0.75). Four of 59 RYGB
      subjects (6.8%) had 1 to 3 hospitalizations for symptomatic hypoglycemia vs 0 in
      SG. The static beta-cell glucose sensitivity index increased after both
      treatments (P < 0.001), but the dynamic beta-cell glucose sensitivity index
      increased significantly in SG (P = 0.008) and decreased in RYGB (P = 0.004 for
      time * treatment interaction). Whole-body insulin sensitivity increased about 10
      fold in both groups. Conclusions: We show that reactive hypoglycemia is no less
      common after SG and is not a safer option than RYGB, but RYGB is associated with
      more severe hypoglycemic episodes. This is likely due to the lack of improvement
      of beta-cell sensitivity to changes in circulating glucose after RYGB, which
      determines an inappropriately high insulin secretion.

PMID- 29590422
TI  - Veteran Experiences Seeking Non-pharmacologic Approaches for Pain.
AB  - Introduction: Pain is a longstanding and growing concern among US military
      veterans. Although many individuals rely on medications, a growing body of
      literature supports the use of complementary non-pharmacologic approaches when
      treating pain. Our objective is to characterize veteran experiences with and
      barriers to accessing alternatives to medication (e.g., non-pharmacologic
      treatments or non-pharmacologic approaches) for pain in primary care. Materials
      and Methods: Data for this qualitative analysis were collected as part of the
      Effective Screening for Pain (ESP) study (2012-2017), a national randomized
      controlled trial of pain screening and assessment methods. This study was
      approved by the Veterans Affairs (VA) Central IRB and veteran participants signed
      written informed consent. We recruited a convenience sample of US military
      veterans in four primary care clinics and conducted semi-structured interviews
      (25-65 min) elucidating veteran experiences with assessment and management of
      pain in VA Healthcare Systems. We completed interviews with 36 veterans,
      including 7 females and 29 males, from three VA health care systems. They ranged
      in age from 28 to 94 yr and had pain intensity ratings ranging from 0 to 9 on the
      "pain now" numeric rating scale at the time of the interviews. We analyzed
      interview transcripts using constant comparison and produced mutually agreed upon
      themes. Results: Veteran experiences with and barriers to accessing complementary
      non-pharmacologic approaches for pain clustered into five main themes:
      communication with provider about complementary approaches ("one of the best
      things the VA has ever given me was pain education and it was through my
      occupational therapist"), care coordination ("I have friends that go to small
      clinic in [area A] and I still see them down in [facility in area B] and they're
      going through headaches upon headaches in trying to get their information to
      their primary care docs"), veteran expectations about pain experience ("I think
      as a society we have shifted the focus to if this doctor doesn't relieve me of my
      pain I will find someone who does"), veteran knowledge and beliefs about various
      complementary non-pharmacologic approaches ("how many people know that tai chi
      will help with pain?... Probably none. I saw them doing tai chi down here at the
      VA clinic and the only reason I knew about it was because I saw it being done"),
      and access ("the only physical therapy I ever did... it helped...but it was a two
      and-a-half-hour drive to get there three times a week... I can't do this").
      Specific access barriers included local availability, time, distance, scheduling
      flexibility, enrollment, and reimbursement. Conclusion: The veterans in this
      qualitative study expressed interest in using non-pharmacologic approaches to
      manage pain, but voiced complex multi-level barriers. Limitations of our study
      include that interviews were conducted only in five clinics and with seven female
      veterans. These limitations are minimized in that the clinics covered are diverse
      ranging to include urban, suburban, and rural residents. Future implementation
      efforts can learn from the veterans' voice to appropriately target veteran
      concerns and achieve more patient-centered pain care.

PMID- 29590423
TI  - The first 5 years of Part 2A Orders: the use of powers from court applications to
      protect public health in England 2010-15.
AB  - Background: Part 2A Orders are the legal means which allow local authorities
      (LAs), upon application to court, to exercise powers over persons, things or
      premises to protect public health. Methods: We surveyed lead professionals
      involved in applications to understand the use and utility of such Orders since
      their inception in April 2010 to July 2015. Results: All applications for Orders
      were granted; 29 for persons (28 for tuberculosis, 1 for HIV); these were renewed
      in 18 (18/25, 72%) cases up to seven times; 23 applications related to things
      (tattoo and piercing equipment); and three applications related to 'premises'
      (Escherichia coli 0137 on farm, faecal contamination). Use of the Orders against
      things occurred where there was failure of the Health and Safety Executive to
      transfer powers to LAs. Orders against persons were used as a last resort and
      renewed until treatment completion in the minority of cases (n = 3). One patient
      was detained under quarantine powers while assessing infectiousness. Significant
      difficulties in implementing the Part 2A Orders due to lack of resources,
      facilities and interagency collaboration were reported. Conclusions: Part 2A
      Orders are used as a last resort but improved facilities for safe and secure
      isolation would help improve implementation.

PMID- 29590424
TI  - The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant,
      1p/19q-intact lower-grade glioma: a validation study.
AB  - Background: The purpose of this study was to assess the reproducibility of the
      previously described T2-fluid attenuated inversion recovery (FLAIR) mismatch sign
      as a specific imaging marker in non-enhancing isocitrate dehydrogenase (IDH)
      mutant, 1p/19q non-codeleted lower-grade glioma (LGG), encompassing both diffuse
      and anaplastic astrocytoma. Methods: MR scans (n = 154) from 3 separate databases
      with genotyped LGG were evaluated by 2 independent reviewers to assess (i)
      presence/absence of "T2-FLAIR mismatch" sign and (ii) presence/absence of
      homogeneous signal on T2-weighted images. Interrater agreement with Cohen's kappa
      (kappa) was calculated, as well as diagnostic test performance of the T2-FLAIR
      mismatch sign to identify IDH-mutant astrocytoma. Results: There was substantial
      interrater agreement for the T2-FLAIR mismatch sign [kappa = 0.75 (0.64-0.87)],
      but only fair agreement for T2 homogeneity [kappa = 0.38 (0.25-0.52)]. The T2
      FLAIR mismatch sign was present in 38 cases (25%) and had a positive predictive
      value of 100%, negative predictive value of 68%, a sensitivity of 51%, and a
      specificity of 100%. Conclusions: With a robust interrater agreement, our study
      confirms that among non-enhancing LGG the T2-FLAIR mismatch sign represents a
      highly specific imaging marker for IDH-mutant astrocytoma. This non-invasive
      marker may enable a more informed patient counsel and can aid in the treatment
      decision processes in a significant proportion of patients presenting with non
      enhancing, LGG-like lesions.

PMID- 29590425
TI  - miR-106a Increases Granulosa Cell Viability and Is Downregulated in Women With
      Diminished Ovarian Reserve.
AB  - Context: Women with diminished ovarian reserve (DOR) have reduced fertility,
      cardiovascular events, and osteoporosis. Although differential microRNA (miRNA)
      expression has been described in several ovarian disorders, little is known about
      the role of miRNAs in the pathogenesis of DOR. Objective: Identify differentially
      expressed miRNAs in DOR and explore the role of miR-106a in human granulosa cell
      proliferation. Design: miRNA microarray (n = 3) and quantitative reverse
      transcription polymerase chain reaction (n = 30) were used to examine miRNA
      expression in serum and granulosa cells from normal-cycling and women with DOR.
      Primary human granulosa cells were treated alone or in combination with miR-106a
      mimic, miR-106a inhibitor, apoptosis signal-regulating kinase 1 (ASK1) small
      interfering RNA (siRNA), or p38 mitogen-activated protein kinase (MAPK) inhibitor
      (SB203580) before assessment of cell viability and apoptosis. Western blot was
      used to measure ASK1 protein and phosphorylation/activation of p38 MAPK. Binding
      of miR-106a to ASK1 mRNA was examined by 3' untranslated region (3'UTR)
      luciferase analysis. Results: Fifteen miRNAs were differentially expressed (n =
      30), and miR-106a was downregulated in serum and granulosa cells of women with
      DOR. miR-106a mimic increased cell viability and attenuated apoptosis, whereas
      the converse occurred following treatment with miR-106a inhibitor. miR-106a
      suppressed ASK1 expression by directly targeting its 3'UTR. miR-106a inhibitor
      increased p38 MAPK phosphorylation/activation, and this effect was abolished by
      treatment with ASK1 siRNA. Whereas knockdown of ASK1 abolished the effects of miR
      106a inhibitor on cell viability/apoptosis, pretreatment with SB203580 did not
      significantly alter the effects of miR-106a inhibitor. Conclusions:
      Downregulation of miR-106a may contribute to the pathogenesis of DOR by reducing
      granulosa cell viability and promoting apoptosis via enhanced ASK1 signaling.

PMID- 29590426
TI  - Taking Charge: Moving from Peer to Supervisor.
AB  - Leadership transitions occur frequently, and these times can be challenging for
      the individual and those they lead. Leaders must develop new knowledge and skills
      required of the position. Leaders also assume a new formal leadership role over
      prior peers. This can be a difficult task for junior leaders. The following
      article illustrates an example case faced by a junior Navy Medical Corps Officer
      and how one might respond.

PMID- 29590427
TI  - The Commander's Wellness Program: Assessing the Association Between Health
      Measures and Physical Fitness Assessment Scores, Fitness Assessment Exemptions,
      and Duration of Limited Duty.
AB  - Introduction: Air Force Medical Service health promotions staff have identified a
      set of evidenced-based interventions targeting tobacco use, sleep habits,
      obesity/healthy weight, and physical activity that could be integrated, packaged,
      and deployed as a Commander's Wellness Program. The premise of the program is
      that improvements in the aforementioned aspects of the health of unit members
      will directly benefit commanders in terms of members' fitness assessment scores
      and the duration of periods of limited duty. The purpose of this study is to
      validate the Commander's Wellness Program assumption that body mass index (BMI),
      physical activity habits, tobacco use, sleep, and nutritional habits are
      associated with physical fitness assessment scores, fitness assessment
      exemptions, and aggregate days of limited duty in the population of active duty
      U.S. Air Force personnel. Methods: This study used a cross-sectional analysis of
      active duty U.S. Air Force personnel with an Air Force Web-based Health
      Assessment and fitness assessment data during fiscal year 2013. Predictor
      variables included age, BMI, gender, physical activity level (moderate physical
      activity, vigorous activity, and muscle activity), tobacco use, sleep, and
      dietary habits (consumption of a variety of foods, daily servings of fruits and
      vegetables, consumption of high-fiber foods, and consumption of high-fat foods).
      Nonparametric methods were used for the exploratory analysis and parametric
      methods were used for model building and statistical inference. Results: The
      study population comprised 221,239 participants. Increasing BMI and tobacco use
      were negatively associated with the outcome of composite fitness score.
      Increasing BMI and tobacco use and decreasing sleep were associated with an
      increased likelihood for the outcome of fitness assessment exemption status.
      Increasing BMI and tobacco use and decreasing composite fitness score and sleep
      were associated with an increased likelihood for the outcome of limited duty
      status, whereas increasing BMI and decreasing sleep were associated with the
      outcome of increased aggregate days of limited duty. The observed associations
      were in the expected direction and the effect sizes were modest. Physical
      activity habits and nutritional habits were not observed to be associated with
      any of the outcome measures. Conclusions: The Commander's Wellness Program should
      be scoped to those interventions targeting BMI, composite fitness score, sleep,
      and tobacco use. Although neither self-reported physical activity nor nutritional
      habits were associated with the outcomes, it is still worthwhile to include
      related interventions in the Commander's Wellness Program because of the finding
      in other studies of a consistent association between the overall number of health
      risks and productivity outcomes.

PMID- 29590428
TI  - Personality Factors and Their Impact on PTSD and Post-traumatic Growth is
      Mediated by Coping Style Among OIF/OEF Veterans.
AB  - Introduction: Traumatic experiences can trigger negative effects such as post
      traumatic stress disorder (PTSD). However, some individuals may also experience
      positive changes following trauma exposure. These changes are known as post
      traumatic growth (PTG). Dispositional and situational factors are likely at play
      in determining both severity of PTSD symptoms and whether and to what degree an
      individual experiences PTG. This study examined how coping style and personality
      traits interact to influence PTSD and PTG. Materials and Methods: Two hundred and
      seventy-one Operation Iraqi Freedom/Operation Enduring Freedom veterans not
      engaged in mental health treatment completed self-report measures of trauma
      exposure, personality traits, coping styles, PTSD symptoms, and PTG. The study
      was approved by the Minneapolis VAHCS Institutional Review Board. Results:
      Adaptive coping and positive personality traits such as openness were positively
      correlated with PTG. Maladaptive coping and neuroticism were positively
      correlated with PTSD symptoms. Regression analyses indicated that an inverted-U
      (quadratic) curve characterized the relationship between PTSD symptoms and PTG;
      veterans who reported moderate PTSD levels reported the most PTG. Mediation
      analyses revealed that adaptive coping partially mediated the relationship
      between openness and PTG. Maladaptive coping partially mediated the relationship
      between neuroticism and PTSD symptoms. Conclusion: This study demonstrated that
      coping style mediated relationships between personality traits and post-trauma
      outcomes. Our findings are subject to the limitations of the self-report and
      cross-sectional nature of the data. Longitudinal studies, preferably
      incorporating coping-oriented interventions, could convincingly demonstrate the
      impact of coping style on PTSD and PTG. As coping styles can be modified, our
      findings nonetheless suggest that coping-oriented clinical intervention has
      potential to reduce PTSD symptoms and promote positive growth following trauma
      exposure.

PMID- 29590429
TI  - Photosynthetic limitation as a factor influencing yield in highbush blueberries
      (Vaccinium corymbosum) grown in a northern European environment.
AB  - Published evidence indicates that nearly 60% of blueberry-producing countries
      experience yield instability. Yield is a complex trait determined by genetic and
      environmental factors. Here, using physiological and biochemical approaches, we
      tested the hypothesis that yield instability results from year-to-year
      environmental variation that limits carbon assimilation, storage and
      partitioning. The data indicate that fruit development depends primarily on the
      daily production of non-structural carbohydrates by leaves, and there is no
      accumulation of a starch buffer to allow continuous ripening under conditions
      limiting for photosynthesis. Photosynthesis was saturated at moderate light
      irradiance and this was mainly due to stomatal and biochemical limitations. In a
      dynamic light environment, photosynthesis was further limited by slow stomatal
      response to increasing light. Finally, labelling with 13CO2 at specific stages of
      fruit development revealed a relatively even distribution of newly assimilated
      carbon between stems, roots and fruits, suggesting that the fruit is not a strong
      sink. We conclude that a significant component of yield variability results from
      limitations in photosynthetic efficiency that are compounded by an inability to
      accumulate starch reserves in blueberry storage tissues in a typical northern
      European environment. This work informs techniques for improving agronomic
      management and indicates key traits required for yield stability in such
      environments.

PMID- 29590431
TI  - An overview of future EU health systems. An insight into governance, primary
      care, data collection and citizens' participation.
AB  - Background: Health systems in the European Union (EU) are being questioned over
      their effectiveness and sustainability. In pursuing both goals, they have to
      conciliate coexisting, not always aligned, realities. Methods: This paper
      originated from a workshop entitled 'Health systems for the future' held at the
      European Parliament. Experts and decision makers were asked to discuss measures
      that may increase the effectiveness and sustainability of health systems, namely:
      (i) increasing citizens' participation; (ii) the importance of primary care in
      providing integrated services; (iii) improving the governance and (iv) fostering
      better data collection and information channels to support the decision making
      process. Results: In the parliamentary debate, was discussed the concept that, in
      the near future, health systems' effectiveness and sustainability will very much
      depend on effective access to integrated services where primary care is pivotal,
      a clearer shift from care-oriented systems to health promotion and prevention, a
      profound commitment to good governance, particularly to stakeholders
      participation, and a systematic reuse of data meant to build health data-driven
      learning systems. Conclusions: Many health issues, such as future health systems
      in the EU, are potentially transformative and hence an intense political issue.
      It is policy-making leadership that will mostly determine how well EU health
      systems are prepared to face future challenges.

PMID- 29590430
TI  - The fungal phytotoxin lasiojasmonate A activates the plant jasmonic acid pathway.
AB  - Jasmonates are signaling compounds that regulate plant responses to stress.
      Jasmonic acid (JA) is the direct precursor of the bioactive plant hormone JA
      isoleucine (JA-Ile), the ligand of the CORONATINE INSENSITIVE 1-jasmonate ZIM
      domain (COI1-JAZ) co-receptor complex. JA, its methyl ester, and three furanonyl
      esters were recently isolated from the grapevine pathogen Lasiodiplodia
      mediterranea. The JA ester lasiojasmonate A (LasA) is the first reported
      naturally occurring JA-furanone, and its mode of action has not yet been
      elucidated. Here, we show that LasA activates many JA-regulated responses in
      planta, including protein degradation, gene expression, and physiological
      processes. These in vivo effects require LasA conversion into JA, formation of JA
      Ile, and its recognition by the plant JA-Ile perception complex. These findings
      suggest a mode of action of the natural fungal LasA as an inactive JA pool that
      can be transformed into the bioactive JA-Ile form. We propose that fungal
      production of JA derivates such as LasA occurs at late infection stages to induce
      plant JA responses such as cell death, and can facilitate fungal infection.

PMID- 29590432
TI  - Myositis in bilateral calves mimicking lymphoma on interim PET/CT in a patient
      with T-lymphoblastic lymphoma.

PMID- 29590433
TI  - Interaction of nitric oxide with the components of the plant mitochondrial
      electron transport chain.
AB  - Mitochondria are not only major sites for energy production but also participate
      in several alternative functions, among these generation of nitric oxide (NO),
      and its different impacts on this organelle, is receiving increasing attention.
      The inner mitochondrial membrane contains the chain of protein complexes, and
      electron transfer via oxidation of various organic acids and reducing equivalents
      leads to generation of a proton gradient that results in energy production.
      Recent evidence suggests that these complexes are sources and targets for NO.
      Complex I and rotenone-insensitive NAD(P)H dehydrogenases regulate hypoxic NO
      production, while complex I also participates in the formation of a supercomplex
      with complex III under hypoxia. Complex II is a target for NO which, by
      inhibiting Fe-S centres, regulates reactive oxygen species (ROS) generation.
      Complex III is one of the major sites for NO production, and the produced NO
      participates in the phytoglobin-NO cycle that leads to the maintenance of the
      redox level and limited energy production under hypoxia. Expression of the
      alternative oxidase (AOX) is induced by NO under various stress conditions, and
      evidence exists that AOX can regulate mitochondrial NO production. Complex IV is
      another major site for NO production, which can also be linked to ATP generation
      via the phytoglobin-NO cycle. Inhibition of complex IV by NO can prevent oxygen
      depletion at the frontier of anoxia. The NO production and action on various
      complexes play a major role in NO signalling and energy metabolism.

PMID- 29590434
TI  - An E2F7-dependent transcriptional program modulates DNA damage repair and genomic
      stability.
AB  - The cellular response to DNA damage is essential for maintaining the integrity of
      the genome. Recent evidence has identified E2F7 as a key player in DNA damage
      dependent transcriptional regulation of cell-cycle genes. However, the
      contribution of E2F7 to cellular responses upon genotoxic damage is still poorly
      defined. Here we show that E2F7 represses the expression of genes involved in the
      maintenance of genomic stability, both throughout the cell cycle and upon
      induction of DNA lesions that interfere with replication fork progression.
      Knockdown of E2F7 leads to a reduction in 53BP1 and FANCD2 foci and to fewer
      chromosomal aberrations following treatment with agents that cause interstrand
      crosslink (ICL) lesions but not upon ionizing radiation. Accordingly, E2F7
      depleted cells exhibit enhanced cell-cycle re-entry and clonogenic survival after
      exposure to ICL-inducing agents. We further report that expression and functional
      activity of E2F7 are p53-independent in this context. Using a cell-based assay,
      we show that E2F7 restricts homologous recombination through the transcriptional
      repression of RAD51. Finally, we present evidence that downregulation of E2F7
      confers an increased resistance to chemotherapy in recombination-deficient cells.
      Taken together, our results reveal an E2F7-dependent transcriptional program that
      contributes to the regulation of DNA repair and genomic integrity.

PMID- 29590435
TI  - Sodium fluxes and silicon at the root plasma membrane: a paradigm shift?

PMID- 29590436
TI  - Testing Mediators of Reduced Drinking for Veterans in Alcohol Care Management.
AB  - Introduction: Alcohol Care Management (ACM) is a manualized treatment provided by
      behavioral health providers working in a primary care team aimed at increasing
      patients' treatment engagement and decreasing their alcohol use. Research has
      shown that ACM is effective in reducing alcohol consumption; however, the
      mechanisms of ACM are unknown. Therefore, the purpose of this study is to examine
      the mechanisms of change in ACM in the context of a randomized clinical trial
      evaluating the effectiveness of ACM. Materials and Methods: This study performed
      secondary data analysis of existing data from a larger study that involved a
      sample of U.S. veterans (N = 163) who met criteria for current alcohol
      dependence. Upon enrollment into the study, participants were randomized to
      receive either ACM or standard care. ACM was delivered in-person or by telephone
      within the primary care clinic and focused on the use of oral naltrexone and
      manualized psychosocial support. According to theory, we hypothesized several ACM
      treatment components that would mediate alcohol consumption outcomes: engagement
      in addiction treatment, reduced craving, and increased readiness to change.
      Parallel mediation models were performed by the PROCESS macro Model 4 in SPSS to
      test study hypotheses. The institutional review boards at each of the
      participating facilities approved all study procedures before data collection.
      Results: As hypothesized, results showed that treatment engagement mediated the
      relation between treatment and both measures of alcohol consumption outcomes, the
      percentage of alcohol abstinent days, and the percentage of heavy drinking days.
      Neither craving nor readiness to change mediated the treatment effect on either
      alcohol consumption outcome. Conclusions: Findings suggest that ACM may be
      effective in changing drinking patterns partially due to an increase in treatment
      engagement. Future research may benefit from evaluating the specific factors that
      underlie increased treatment engagement. The current study provides evidence that
      alcohol use disorder interventions should aim to increase treatment engagement
      and reduce barriers to care.

PMID- 29590437
TI  - Insulin Resistance and beta-Cell Dysfunction in Relation to Cardiometabolic Risk
      Patterns.
AB  - Context: Insulin resistance (IR) and beta-cell dysfunction are two major defects
      synergistically inducing the development of diabetes and related cardiometabolic
      disorders. Objective: To investigate the independent and joint associations of IR
      and beta-cell dysfunction with the prevalence of multiple cardiometabolic
      disorders, including obesity, central obesity, diabetes, dyslipidemia, and
      hypertension. Design and Settings: A nationally representative population of
      93,690 Chinese adults. Main Outcome Measures: IR and beta-cell dysfunction were
      assessed by the homeostasis model assessment of IR (HOMA-IR) and of beta-cell
      function (HOMA-B), respectively. Results: High HOMA-IR was independently
      associated with high prevalence of all estimated cardiometabolic disorders,
      whereas low HOMA-B was independently associated with high prevalence of diabetes,
      dyslipidemia, and hypertension but low prevalence of obesity and central obesity.
      When examined jointly, the associations of HOMA-IR and HOMA-B with multiple
      cardiometabolic disorders showed different patterns with varying magnitudes. The
      strongest joint associations were observed for diabetes, with low HOMA-B
      associated with high prevalence of diabetes regardless of HOMA-IR; joint
      associations with dyslipidemia and hypertension prevalence appeared to be
      additive and had moderate changing trends; and low HOMA-B was not associated with
      high prevalence of obesity or central obesity unless combined with high HOMA-IR.
      Conclusion: IR was associated with more prevalent cardiometabolic disorders than
      was beta-cell dysfunction, and combinations of IR and beta-cell dysfunction
      showed distinct relations with cardiometabolic risk patterns in Chinese adults.

PMID- 29590438
TI  - Recommendations for Counseling and Education of Service Members on Endemic
      African Cutaneous Kaposi Sarcoma: A Case Study.
AB  - We report a case of Endemic African Cutaneous Kaposi Sarcoma (EACKS) on the lower
      extremity of an immunocompetent 31-yr-old male service member from Cameroon.
      Diagnosis was made using clinical and histologic findings. The service member was
      treated with local radiation therapy with resolution of his tumor.The goal of
      this article is to educate practitioners to counsel susceptible service members
      and leadership on the risk of developing EACKS when traveling to Sub-Saharan
      Africa, monitor for disease development, and guide in the diagnosis and treatment
      of patients with this rare disease.

PMID- 29590439
TI  - Paul D. Sturkie: Avian cardiac physiologist.
AB  - Sturkie's Avian Physiology is a highly regarded textbook for the study of
      comparative poultry physiology. Less well known, however, is the contribution of
      Paul D. Sturkie (1909-2002) as a pioneer in the experimental physiology of avian
      species. His seminal research on the cardiovascular and hemodynamic controls of
      chickens and egg-laying hens had a notable impact on the poultry industry and
      breeding practices of farmers. The purpose of this article is to highlight the
      contributions and practical insights of Paul D. Sturkie to the field of poultry
      science.

PMID- 29590440
TI  - Differences in egg nutrient availability and embryo development in white layer
      breeder genotypes.

PMID- 29590441
TI  - Letter: Role of Tyrosine Kinase Inhibitors in Recurrent Meningiomas:
      Controversies and Promises.

PMID- 29590442
TI  - Faith in the Common Ground.

PMID- 29590443
TI  - The neurophysiological basis of the discrepancy between objective and subjective
      sleep during the sleep onset period: an EEG-fMRI study.
AB  - Subjective perception of sleep is not necessarily consistent with
      electroencephalography (EEG) indications of sleep. The mismatch between
      subjective reports and objective measures is often referred to as "sleep state
      misperception." Previous studies evince that this mismatch is found in both
      patients with insomnia and in normal sleepers, but the neurophysiological
      mechanism remains unclear. The aim of the study is to explore the
      neurophysiological basis of this mechanism, from the perspective of both EEG
      power and functional magnetic resonance imaging (fMRI) fluctuations. Thirty-six
      healthy young adults participated in the study. Simultaneous EEG and fMRI
      recordings were conducted while the participants were trying to fall asleep in an
      MRI scanner at approximately 9:00 pm. They were awakened after achieving stable
      N1 or N2 sleep, or after 90 min without falling into stable sleep. Next they were
      asked to recall their conscious experiences from the moment immediately prior to
      awakening. Sixty-one instances of scheduled awakenings were collected: 21 of
      these after having achieved stable stage N2 sleep; 12, during stage N1 sleep;
      and, 20 during the waking state. Relative to those awakenings without subjective
      objective discrepancy (n = 27), these awakenings with discrepancy (n = 14) were
      associated with lower theta power, as well as higher alpha, beta, and gamma
      power. Moreover, we found that participants who exhibited the discrepancy,
      compared with those who did not, evinced a higher amplitude of low-frequency
      fluctuation levels in the prefrontal cortex. These results lend support to the
      conjecture that the subjective-objective discrepancy is associated with central
      nervous system hyperarousal.

PMID- 29590444
TI  - Extremely Delayed Diagnosis of Type II Hereditary Angioedema: Case Report and
      Review of the Literature.
AB  - We present a case with extremely late diagnosis of type II hereditary angioedema
      (HAE). Given recent advances in HAE treatment, we want to bring physician
      awareness to this condition and aid in earlier detection. HAE is a disorder
      associated with episodes of angioedema of the face, larynx, lips, abdomen, or
      extremities. Late diagnosis of HAE can lead to significant morbidity and is
      severely impairing due to recurring attacks. The diagnosis of HAE is ordinarily
      made during childhood and adolescence. Delayed diagnoses in early and middle
      adulthood have been documented in the literature. Gastrointestinal symptoms are
      common features of HAE and can be misdiagnosed as disease of primary
      gastrointestinal pathology, such as irritable bowel syndrome, recurrent
      pancreatitis, or appendicitis. These attacks are characterized by recurrent
      attacks of subcutaneous and submucosal edema without the presence of urticaria.We
      present a case of an elderly veteran whose diagnoses was extremely delayed into
      the eighth decade of life subsequent to unexplained abdominal symptoms. After
      diagnosis, the patient's symptoms were well controlled with medication due to
      advances in HAE treatment. To prevent further atypically delayed diagnoses,
      physicians should consider HAE in patients with recurrent attacks of unexplained
      abdominal pain.

PMID- 29590445
TI  - Atlantoaxial Instability in a Patient with Neck Pain and Ankylosing Spondylitis.
AB  - The purpose of this report is to describe the evaluation and treatment of a
      patient with neck pain and ankylosing spondylitis who had underlying atlantoaxial
      instability. The patient was a 31-yr-old man diagnosed with ankylosing
      spondylitis 1 yr prior who was referred to a physical therapist for the treatment
      of chronic, worsening low back and hip pain. He also had secondary complaints of
      neck, upper back, and shoulder pain. The patient worked as a military pilot. As
      part of the patient's physical examination, a Sharp-Purser test was performed,
      which was positive for excessive motion. Diagnostic imaging confirmed the
      atlantoaxial instability; it was also determined that the patient's atlanto
      occipital joints were fused. Despite evidence of atlantoaxial instability, it was
      determined the patient would be managed through nonsurgical interventions. The
      patient was prescribed etanercept by his rheumatologist and the physical
      therapist developed a comprehensive rehabilitation program that addressed
      relevant impairments of the spine, hips, and shoulders. At 3 yr following his
      initial evaluation with the physical therapist, the patient continued to report
      minimal bodily pain and no limitations in his functional capabilities.
      Additionally, the patient had earned a high profile flying position with an
      aggressive flying schedule and he successfully completed his first running
      marathon. It is important for clinicians to have an understanding of the clinical
      findings associated with atlantoaxial instability, as these findings provide
      guidance for diagnostic imaging and specialist referral prior to initiating
      conservative management strategies, such as physical therapy.

PMID- 29590446
TI  - Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer
      Pain, Reduces Pain, and Improves Quality of Life.
AB  - Objectives: More than half of the patients have reported improper management of
      breakthrough cancer pain. Empirical evidence is lacking concerning the
      effectiveness of cancer pain education on breakthrough pain control. This study
      aimed to examine the effects of individual pain education on pain control, use of
      short-acting analgesics for breakthrough pain, quality of life outcomes, and
      rectification of patients' misconceptions regarding cancer pain. Design: A quasi
      experimental design was used. In total, 176 (102 inpatients and 74 outpatients)
      and 163 (93 inpatients and 70 outpatients) cancer patients completed
      questionnaires on pain intensity, quality of life, use of short-acting medication
      for breakthrough pain, and misconceptions about cancer pain and opioid use before
      and immediately and/or seven days after individual pain education. Results: The
      mean age of the participants was 60.9 years (+/-11.2), and 56.3% were male. The
      most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast
      cancer (12.5%). The subjects' reasons for attrition were conditional
      deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the
      education, there was a significant reduction in overall pain intensity over 24
      hours (P < 0.001). The outpatients showed more use of short-acting analgesics for
      breakthrough pain. Sleep quality change was most significantly associated with
      intervention; other quality of life aspects (e.g., general feelings and life
      enjoyment) also improved. Pain education also significantly reduced
      misconceptions regarding cancer pain management. Conclusions: The present
      educational intervention was effective in encouraging short-acting analgesic use
      for breakthrough pain, improving quality of life outcomes, and rectifying
      patients' misconceptions about analgesic use.

PMID- 29590447
TI  - Staying Power: Does the Uniformed Services University Continue to Meet Its
      Obligation to the Nation's Health Care Needs?
AB  - Introduction: The Uniformed Services University F. Edward Hebert School of
      Medicine just passed its 45th anniversary, opening in 1972. A goal of the medical
      school, like those nationally, is the production of high-quality physicians. The
      purpose of this study is to describe the practice characteristics of our USU
      graduates and to compare data with the national cohort of U.S. MD graduates.
      Materials and Methods: To accomplish this, we performed a retrospective analysis
      of U.S. graduates (1980-2009). We used the American Medical Association Physician
      Masterfile to describe our graduates' current practice profile and compare them
      with the national cohort. In order to ascertain if USU is meeting our goal to
      provide high-quality physicians, we also compare our findings with national
      allopathic school data to norm-reference our results. Results: Our findings
      indicate that USU graduates contribute to both primary care and specialty care
      and they practice in all 50 states. USU graduates continue to serve their nation
      after their obligation is complete, with 64% continuing to practice in federal
      hospitals and agencies. USU graduates also have a higher board certification rate
      (90%) than the national cohort (88%). Conclusion: Following our 45th anniversary,
      we provide continuing evidence that USU is keeping its contract with society. We
      provide evidence that USU continues to meet its obligation to the nation's health
      care needs by producing high-quality physicians who serve the country in multiple
      ways after their military obligation is complete, thus extending the definition
      of staying power. Our study is not without limitations. First, we could not
      precisely define the cohort to exclude graduates who still had service
      obligations. Second, the AMA Physician Masterfile had some missing data fields,
      so nonresponse or misclassification bias is possible in our results. Study
      strengths include the long period of time and large number of graduates in each
      cohort.

PMID- 29590448
TI  - 18F-fluorodeoxyglucose positron emission tomography to indicate conversion
      surgery in patients with initially unresectable locally advanced pancreatic
      cancer.
AB  - Objective: Advances in chemotherapy and chemoradiotherapy have enabled conversion
      of initially unresectable locally advanced (UR-LA) pancreatic adenocarcinoma
      (PDAC) to a resectable disease. However, definitive criteria for conversion
      surgery have not been established. We evaluated the potential of 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) to indicate conversion
      surgery in patients with primary UR-LA PDAC. Methods: Twenty consecutive patients
      with UR-LA PDAC underwent chemoradiation or chemotherapy followed by assessment
      with FDG-PET. We defined PET responders (standardized uptake value <3.0) with
      marked reduction (>80%) of carbohydrate antigen 19-9 as potential candidates for
      conversion surgery. Outcomes were compared with those of the patients with
      resectable (R; n = 94) and borderline resectable (BR; n = 37) PDAC. Results:
      Eight of the 20 patients (40%) were considered PET responders with marked
      reduction of CA19-9 and received conversion surgery (UR-LAR) 3-9 months (median,
      5 months) after the initiation of therapy. Complete resection (R0) was achieved
      in 7 of 8 patients (87.5%) with UR-LAR. There was no significant difference in R0
      rates, morbidity, or mortality among the UR-LAR, R and BR groups. The overall
      survival (OS) curve was better in the UR-LAR group than in the group that did not
      receive surgery. There was no significant difference in OS between the UR-LAR and
      the R or BR groups. Conclusions: FDG-PET could be a potential indicator for
      conversion surgery in patients with primary UR-LA PDAC and may help in selecting
      patients who qualify for complete surgical resection and have a promising
      prognosis.

PMID- 29590449
TI  - Cancer Incidence in Patients With Acromegaly: A Cohort Study and Meta-Analysis of
      the Literature.
AB  - Context: Acromegaly has been associated with increased risk of cancer morbidity
      and mortality, but research findings remain conflicting and population-based data
      are scarce. We therefore examined whether patients with acromegaly are at higher
      risk of cancer. Design: A nationwide cohort study (1978 to 2010) including 529
      acromegaly cases was performed. Incident cancer diagnoses and mortality were
      compared with national rates estimating standardized incidence ratios (SIRs). A
      meta-analysis of cancer SIRs from 23 studies (including the present one) was
      performed. Results: The cohort study identified 81 cases of cancer after
      exclusion of cases diagnosed within the first year [SIR 1.1; 95% confidence
      interval (CI), 0.9 to 1.4]. SIRs were 1.4 (95% CI, 0.7 to 2.6) for colorectal
      cancer, 1.1 (95% CI, 0.5 to 2.1) for breast cancer, and 1.4 (95% CI, 0.6 to 2.6)
      for prostate cancer. Whereas overall mortality was elevated in acromegaly (SIR
      1.3; 95% CI, 1.1 to 1.6), cancer-specific mortality was not. The meta-analysis
      yielded an SIR of overall cancer of 1.5 (95% CI, 1.2 to 1.8). SIRs were elevated
      for colorectal cancer, 2.6 (95% CI, 1.7 to 4.0); thyroid cancer, 9.2 (95% CI, 4.2
      to 19.9); breast cancer, 1.6 (1.1 to 2.3); gastric cancer, 2.0 (95% CI, 1.4 to
      2.9); and urinary tract cancer, 1.5 (95% CI, 1.0 to 2.3). In general, cancer SIR
      was higher in single-center studies and in studies with <10 cancer cases.
      Conclusions: Cancer incidence rates were slightly elevated in patients with
      acromegaly in our study, and this finding was supported by the meta-analysis of
      23 studies, although it also suggested the presence of selection bias in some
      earlier studies.

PMID- 29590450
TI  - The Ups and Downs of Cognitive Function: Neuroticism and Negative Affect Drive
      Performance Inconsistency.
AB  - Objectives: Response time inconsistency (RTI)-or trial-to-trial variability in
      speeded performance-is increasingly recognized as an indicator of transient
      lapses of attention, cognitive health status, and central nervous system
      integrity, as well as a potential early indicator of normal and pathological
      cognitive aging (Hultsch, Strauss, Hunter, & MacDonald, 2008; MacDonald, Li, &
      Backman, 2009). Comparatively, little research has examined personality
      predictors of RTI across adulthood. Methods: We evaluated the association between
      the personality trait neuroticism and RTI in a community-dwelling sample of 317
      adults between the ages of 19 to 83 and tested for two indirect pathways through
      negative affect (NA) and cognitive interference (CI). Results: The personality
      trait neuroticism predicted greater RTI independent of mean response time
      performance and demographic covariates; the results were age-invariant.
      Furthermore, NA (but not CI) accounted for this association and moderated
      mediation model results indicated that older adults were more vulnerable to the
      adverse effects of NA. Discussion: Neuroticism predicts greater response time
      inconsistency irrespective of mean performance and this effect is driven largely
      by heightened negative emotionality that may be particularly detrimental for
      older adults.

PMID- 29590451
TI  - In Reply: Navigation-Linked Heads-Up Display in Intracranial Surgery: Early
      Experience.

PMID- 29590452
TI  - Exploring the multidisciplinary extent of public health career structures in 12
      countries: an exploratory mapping.
AB  - Background: While much is known about multidisciplinary public health (MDPH)
      professional practice in the UK which developed particularly in the 1990s, little
      is known about it in other settings especially low and middle-income countries
      (LMICs). This study reports on findings of a mapping review of public health
      career structures and an examination of how multidisciplinary they are in 12
      countries. Methods: A 12-element template was used to collect data from relevant
      websites and key informants with public health experience in the 12 countries.
      Results: We found that while countries had similarities such as having MDPH
      professional organizations, there were differences in terms of public health
      specialty training programmes and openness of senior public health posts at
      various administrative levels to non-medical professionals. Conclusion: We
      conclude that there still gaps in MDPH career structures internationally. While
      this study provides preliminary knowledge on the subject, we recommend further
      research to inform debates and policies in MDPH professional practice especially
      in LMICs.

PMID- 29590454
TI  - Erratum.

PMID- 29590453
TI  - Infiltrating history into the public health curriculum.
AB  - The insertion of history into the medical school curriculum has been discussed
      over a long period of time. But the role of history in the public health
      curriculum has not been the subject of much discussion, despite the changes in UK
      public health training and the advent of multidisciplinary public health. This
      article reviews the history of inserting history into the curriculum in a leading
      public health postgraduate institution. It discusses the strategies used to
      secure acceptance for history; the positioning of history within the curriculum
      both as a core and a special subject; and the different curriculum content and
      learning approaches which have been used over time. It reviews recent
      developments in distance learning and the launch of a history Massive Open On
      line Course. It concludes that no one approach can be recommended for inserting
      history and that flexibility, persistence, alliances and the willingness to adapt
      to local circumstances are important. Students themselves are now more receptive
      to historical approaches and can appreciate the value of a discipline which
      teaches critical skills of analysis and assessment of evidence. It remains to be
      discussed how the discipline and such approaches can be transferred into wider
      professional public health training and at the undergraduate level.

PMID- 29590455
TI  - Estimates of Tibial Shock Magnitude in Men and Women at the Start and End of a
      Military Drill Training Program.
AB  - Introduction: Foot drill is a key component of military training and is
      characterized by frequent heel stamping, likely resulting in high tibial shock
      magnitudes. Higher tibial shock during running has previously been associated
      with risk of lower limb stress fractures, which are prevalent among military
      populations. Quantification of tibial shock during drill training is, therefore,
      warranted. This study aimed to provide estimates of tibial shock during military
      drill in British Army Basic training. The study also aimed to compare values
      between men and women, and to identify any differences between the first and
      final sessions of training. Materials and Methods: Tibial accelerometers were
      secured on the right medial, distal shank of 10 British Army recruits (n = 5 men;
      n = 5 women) throughout a scheduled drill training session in week 1 and week 12
      of basic military training. Peak positive accelerations, the average magnitude
      above given thresholds, and the rate at which each threshold was exceeded were
      quantified. Results: Mean (SD) peak positive acceleration was 20.8 (2.2) g across
      all sessions, which is considerably higher than values typically observed during
      high impact physical activity. Magnitudes of tibial shock were higher in men than
      women, and higher in week 12 compared with week 1 of training. Conclusions: This
      study provides the first estimates of tibial shock magnitude during military
      drill training in the field. The high values suggest that military drill is a
      demanding activity and this should be considered when developing and evaluating
      military training programs. Further exploration is required to understand the
      response of the lower limb to military drill training and the etiology of these
      responses in the development of lower limb stress fractures.

PMID- 29590456
TI  - Hydrogen Peroxide Participates in Perception and Transduction of Cold Stress
      Signal in Synechocystis.
AB  - The double mutant DeltakatG/tpx of cyanobacterium Synechocystis sp. strain PCC
      6803, defective in the anti-oxidative enzymes catalase (KatG) and thioredoxin
      peroxidase (Tpx), is unable to grow in the presence of exogenous H2O2. The
      DeltakatG/tpx mutant is shown to be extremely sensitive to very low
      concentrations of H2O2, especially when intensified with cold stress. Analysis of
      gene expression in both wild-type and DeltakatG/tpx mutant cells treated by
      combined cold/oxidative stress revealed that H2O2 participates in regulation of
      expression of cold-responsive genes, affecting either signal perception or
      transduction. The central role of a transmembrane stress-sensing histidine kinase
      Hik33 in the cold/oxidative signal transduction pathway is discussed.

PMID- 29590457
TI  - Auxin-cytokinin interactions in the regulation of correlative inhibition in two
      branched pea seedlings.
AB  - A model system of 10-12 day-old, two-branched (2-B) pea (Pisum sativum L. cv.
      Adagumsky) seedlings was used to study the roles of endogenous auxin indole-3
      acetic acid (IAA) and cytokinins (CKs) in the interaction between the shoots. The
      IAA export activity (IEA) from shoots was 2-fold higher in one-branched (1-B)
      plants with one shoot removed than in the 2-B plants, while tZ-type cytokinin
      contents in xylem sap were 4-fold greater in the 1-B plants than in 2-B plants.
      Exogenous 6-benzylaminopurine introduced into the vascular stream of one shoot
      enhanced its IEA. Therefore, xylem cytokinin appears to control both growth and
      IEA in branches. In the hypocotyls of 1-B and 2-B plants, IAA contents were equal
      in both cases, while the levels of tZ-type cytokinins were different. These data
      do not agree with the well-supported role of auxin in down-regulating CK content.
      The observed paradox may be explained by assuming that a steady-state IAA level
      in the hypocotyls is feedback regulated via xylem cytokinin, which controls the
      delivery of IAA from the shoots. As a result, the level of IAA in the hypocotyl
      is most likely maintained at a threshold below which a decrease in auxin content
      can switch on CK synthesis that will increase xylem cytokinin levels, thereby
      stabilizing the level of IAA in the hypocotyl. Therefore, our results suggest
      that correlative inhibition in the 2-B pea system is a function of an IAA/CK
      feedback loop, in which cytokinin essentially acts as a second messenger for IAA.

PMID- 29590458
TI  - Muscular disorder related to immune checkpoint inhibitors: forewarned is
      forearmed.

PMID- 29590460
TI  - Coffee consumption and reduced risk of developing type 2 diabetes: a systematic
      review with meta-analysis.
AB  - Context: Type 2 diabetes (T2D) is a major health problem worldwide that is
      associated with increased morbidity and mortality. There is increased interest in
      the value of different nutrition-based strategies for preventing the development
      of T2D. Objective: This review aims to cover current knowledge regarding the
      effects of coffee consumption on development of T2D or modulation of adverse
      complications. A meta-analysis on coffee consumption and the risk of T2D was
      conducted. Moreover, bioactive components in coffee, polymorphisms, and potential
      underlying mechanism(s) in relation to T2D and adverse complications are
      discussed. Data sources: PubMed was searched up to December 1, 2017, and
      prospective cohort and nested case-control studies of the association between
      coffee consumption and T2D risk were selected. Data extraction: Two investigators
      independently extracted data from included studies. Results: A total of 30
      prospective studies with 1 185 210 participants and 53 018 incident T2D cases
      were included in the meta-analysis. The pooled relative risk (RR) was 0.71 (95%
      confidence interval [CI], 0.67-0.76) for the highest category of coffee
      consumption (median consumption, 5 cups/d) vs the lowest category (median
      consumption, 0 cups/d). The risk of T2D decreased by 6% (RR = 0.94; 95%CI, 0.93
      0.95) for each cup-per-day increase in coffee consumption. Results were similar
      for caffeinated coffee consumption (per additional cup of coffee per day: RR =
      0.93; 95%CI, 0.90-0.96) and decaffeinated coffee consumption (corresponding RR =
      0.94; 95%CI, 0.90-0.98). Conclusions: Available evidence indicates that coffee
      consumption is inversely associated with risk of T2D. Possible mechanisms behind
      this association include thermogenic, antioxidative, and anti-inflammatory
      effects; modulation of adenosine receptor signaling; and microbiome content and
      diversity.

PMID- 29590459
TI  - Systemic haemodynamics in haemodialysis: intradialytic changes and prognostic
      significance.
AB  - Background: Although haemodialysis (HD) leads to alterations of systemic
      haemodynamics that can be monitored using dilution methods, there is a lack of
      data on the diagnostic and prognostic significance of haemodynamic monitoring
      during routine HD. Methods: In this multicentre study, we measured cardiac index
      (CI), access flow (AF) and central blood volume index (CBVI) during a single HD
      session in stable HD patients (n = 215) using the Transonic HD03 monitor
      (Transonic, Ithaca, NY, USA). Systemic CI (SCI) was defined as CI corrected for
      AF. In a subset of patients (n = 82), total end-diastolic volume index (TEDVI)
      and total ejection fraction (TEF) were derived from dilution curves. Data were
      correlated with clinical parameters, cardiac biomarkers and bioimpedance
      measurements (body composition monitor; Fresenius Medical Care, Homburg,
      Germany). Mortality was assessed prospectively after a median follow-up of 2.6
      years. Results: Median CI, CBVI and AF were 2.8 L/min/m2 (interquartile range 2.4
      3.4), 15 mL/kg (14.5-15.7) and 980 mL/min (740-1415), respectively, at the
      beginning of HD. At the end of HD, CI, CBVI and AF significantly fell by -10% (
      22 to 3, P < 0.0001), -9% (-23 to 3, P < 0.0001) and -4% (-13 to 5, P = 0.0004),
      respectively. Peripheral resistance (PR) increased slightly (P = 0.01) and blood
      pressure fell by -6/-3 mmHg to 128/63 mmHg (P < 0.0001). Independent predictors
      of DeltaCI were age and ultrafiltration rate, whereas AF, overhydration and PR
      were protective. TEF was strongly associated with mortality [area under the
      dilution curve 0.77, P < 0.0001], followed by TEDVI (0.72, P = 0.0002) and SCI
      (0.60, P = 0.02). Conclusions: HD leads to a reduction of CI due to
      ultrafiltration. Haemodynamic monitoring identifies a significant number of HD
      patients with cardiac impairment that are at risk for increased mortality.

PMID- 29590462
TI  - The Epidemiology of Social Isolation: National Health & Aging Trends Study.
AB  - Objectives: Social isolation among older adults is an important but under
      recognized risk for poor health outcomes. Methods are needed to identify
      subgroups of older adults at risk for social isolation. Methods: We constructed a
      typology of social isolation using data from the National Health and Aging Trends
      Study (NHATS) and estimated the prevalence and correlates of social isolation
      among community-dwelling older adults. The typology was formed from four domains:
      living arrangement, core discussion network size, religious attendance, and
      social participation. Results: In 2011, 24% of self-responding, community
      dwelling older adults (65+ years), approximately 7.7 million people, were
      characterized as socially isolated, including 1.3 million (4%) who were
      characterized as severely socially isolated. Multinomial multivariable logistic
      regression indicated that being unmarried, male, having low education, and low
      income were all independently associated with social isolation. Black and
      Hispanic older adults had lower odds of social isolation compared to White older
      adults, after adjusting for covariates. Discussion: Social isolation is an
      important and potentially modifiable risk that affects a significant proportion
      of the older adult population.

PMID- 29590461
TI  - Prognostic value of contrast enhancement and FLAIR for survival in newly
      diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN
      6686.
AB  - Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional
      chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo)
      in newly diagnosed glioblastoma. This study investigated whether changes in
      contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense
      tumor assessed by central reading prognosticate overall survival (OS). Methods:
      Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on
      bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant
      temozolomide (22 wk post chemoradiation initiation). Four central readers
      measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at
      both time points. Changes from baseline to pre-cycle 4 for both markers were
      dichotomized (increasing vs non-increasing). Cox proportional hazards model and
      Kaplan-Meier survival estimates were used for inference. Results: Adjusting for
      treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48
      2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008)
      significantly predicted worse OS. Median OS (days) was significantly shorter for
      patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs
      535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly
      shorter for patients with increasing versus non-increasing FLAIR for placebo (595
      vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P =
      0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented
      significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01).
      Conclusion: Increased 2D-T1 significantly predicts worse OS in both treatment
      groups, implying absence of a substantial proportion of pseudoprogression 22
      weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in
      predicting OS, potentially addressing the pseudoresponse effect by substratifying
      bevacizumab-treated patients with non-increasing 2D-T1.

PMID- 29590463
TI  - Diagnosing IgA Vasculitis in the Active Duty Population: The Importance of Early
      Diagnosis and Proper Biopsy Site Selection.
AB  - Immunoglobulin A associated vasculitis (IgAV), formerly called Henoch-Schonlein
      purpura, is a small vessel vasculitis which typically presents with upper and
      lower extremity palpable purpura and abdominal pain. It is the most common
      vasculitis in children, and is less common in adults. However, newer evidence
      suggests the incidence within the adult population is higher than previously
      reported. This case study demonstrates an adult military recruit presenting with
      new onset IgAV shortly after basic training. He noted a preceding upper
      respiratory tract infection, which is a common finding in those presenting with
      IgAV. The diagnosis was made by clinical findings, histopathological results and
      direct immunofluorescence. Adults tend to develop more necrotic and bullous
      lesions when compared with children. This can skew histopathology and direct
      immunofluorescence. There is no clear consensus in current literature for whether
      to obtain lesional or perilesional biopsies. Such recommendations could be
      particularly advantageous for adults given the abnormal lesions. This case study
      addresses the incidence of IgAV within the adult population, diagnostic criteria,
      long-term sequalea of IgAV, and the importance of a proper biopsy sight when
      making the diagnosis.

PMID- 29590464
TI  - Establishing normal values for pediatric nighttime sleep measured by actigraphy:
      a systematic review and meta-analysis.
AB  - Background: Despite the widespread use of actigraphy in pediatric sleep studies,
      there are currently no age-related normative data. Objectives: To systematically
      review the literature, calculate pooled mean estimates of actigraphy-derived
      pediatric nighttime sleep variables and to examine the magnitude of change with
      age. Methods: A systematic search was performed across eight databases of studies
      that included at least one actigraphy sleep variable from healthy children aged 0
      18 years. Data suitable for meta-analysis were confined to ages 3-18 years with
      seven actigraphy variables analyzed using random effects meta-analysis and meta
      regression performed using age as a covariate. Results: In total, 1334 articles
      did not meet inclusion criteria; 87 had data suitable for review and 79 were
      suitable for meta-analysis. Pooled mean estimates for overnight sleep duration
      declined from 9.68 hours (3-5 years age band) to 8.98, 8.85, 8.05, and 7.4 for
      age bands 6-8, 9-11, 12-14, and 15-18 years, respectively. For continuous data,
      the best-fit (R2 = 0.74) equation for hours over the 0-18 years age range was
      9.02 - 1.04 * [(age/10)^2 - 0.83]. There was a significant curvilinear
      association between both sleep onset and offset with age (p < .001). Sleep
      latency was stable at 19.4 min per night. There were significant differences
      among the older age groups between weekday and weekend/nonschool days (18
      studies). Total sleep time in 15-18 years old was 56 min longer, and sleep onset
      and offset almost 1 and 2 hours later, respectively, on weekend or nonschool
      days. Conclusion: These normative values have potential application to assist the
      interpretation of actigraphy measures from nighttime recordings across the
      pediatric age range, and aid future research.

PMID- 29590466
TI  - Beyond One Hundred: A Cohort Analysis of Italian Centenarians and Semi
      supercentenarians.
AB  - Although the increase in the number of centenarians is well documented today in
      countries with advanced demographic data, the same is not true for those aged 105
      and over. The first aim of this paper, was to analyze the demographic
      characteristics of the 4,626 validated semi-super and 102 supercentenarians for
      the cohorts born between 1896 and 1910, referring to Italian Semi
      Supercentenarians Survey (SSC). Then, starting from this data and from the
      survival  histories  in old ages - reconstructed by Vincent's Extinct - Cohort
      Method - for the cohorts born between 1870 and 1904, the most important aim was
      to analyze longevity history and the trend of gender gap of the Italian oldest
      cohorts beyond 100 years old.  The Italian centenarians and semi
      supercentenarians increase from the first to the last cohort is due to the
      survival rise in old ages and the increase in the gender gap at extreme ages
      depends on the higher survival of women than men after 60 years old. Around 110
      112 for both genders (for women in particular) a kind of resistance to further
      progress seems to appear in our analysis as in more recent studies on
      supercentenarians.

PMID- 29590465
TI  - Population description and clinical response assessment for spinal metastases:
      part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report.
AB  - Background: Approximately 40% of metastatic cancer patients will develop spinal
      metastases. The current report provides recommendations for standardization of
      metrics used for spinal oncology patient population description and outcome
      assessment beyond local control endpoints on behalf of the SPIne response
      assessment in Neuro-Oncology (SPINO) group. Methods: The SPINO group survey was
      conducted in order to determine the preferences for utilization of clinician
      based and patient-reported outcome measures for description of patients with
      spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for
      spinal oncology clinical trials, and measures for patient description and outcome
      reporting were identified for each trial. These two searches were used to
      identify currently used descriptors and instruments. A literature search was
      performed focusing on the measures identified in the survey and clinical trial
      search in order to assess their validity in the metastatic spinal tumor patient
      population. References for this manuscript were identified through PubMed and
      Medline searches. Results: Published literature, expert survey, and ongoing
      clinical trials were used to synthesize recommendations for instruments for
      reporting of spinal stability, epidural tumor extension, neurological and
      functional status, and symptom severity. Conclusions: Accurate description of
      patient population and therapy effects requires a combination of clinician-based
      and patient-reported outcome measures. The current report provides international
      consensus recommendations for the systematic reporting of patient- and clinician
      reported measures required to develop trials applicable to surgery for spinal
      metastases and postoperative spine stereotactic body radiotherapy (SBRT).

PMID- 29590467
TI  - A Retrospective Study of Neonatal Outcome in Preeclampsia at the University
      Hospital of the West Indies: A Resource-limited Setting.
AB  - Aim: This study aimed to determine the outcome of neonates born to women with
      preeclampsia at the University Hospital of the West Indies (UHWI). Methods: This
      was a retrospective descriptive study looking at the outcome of all babies born
      to women with preeclampsia and control babies born to normotensive women at the
      UHWI over a 20-month period. Maternal and neonatal demographic data and course of
      admission for admitted neonates were recorded. Descriptive analyses were
      performed. Results: Neonates born to women with preeclampsia were more likely to
      be low birth weight [odds ratio (OR = 2.8; confidence interval (CI): 2.2-3.5],
      small for gestational age (OR = 2.3; CI: 1.9-2.9) or premature (OR = 2.5; CI: 2.0
      3.0). They had a lower mean 5 min Apgar score than babies born to normotensive
      women p<0.05. They were also more likely to be admitted to the neonatal unit 67
      (59%) compared with neonates of normotensive women 13 (13%) p<0.001. The main
      reason for admission was prematurity. Eighteen neonates, all born to women with
      preeclampsia, died, and the main cause of death was prematurity. Conclusion:
      Adverse neonatal outcome was noted in neonates born to women with preeclampsia,
      and this was predominantly related to prematurity and its complications.

PMID- 29590468
TI  - Re-experiencing Violence across the Life Course: Histories of Childhood
      Maltreatment and Elder Abuse Victimization.
AB  - Objectives: This study primarily examines the associations between histories of
      childhood maltreatment (i.e., neglect, emotional, physical, and sexual abuse) and
      elder abuse victimization and explores whether gender moderates the associations.
      Methods: We conducted a secondary data analysis of 5,968 older adults (mean age =
      71 years) based on data from the Wisconsin Longitudinal Study (2010-2011). Using
      retrospective self-reports of childhood and current (past 12 months)
      victimization experiences, logistic regression analyses were conducted to
      estimate the effects of early-life adversities on the likelihood of elder abuse
      victimization. Results: Results indicate that childhood emotional abuse and
      childhood sexual abuse were associated with greater risk of being abused as older
      adults, after controlling for childhood and adult background factors. We also
      found that the effect of childhood sexual abuse on elder abuse victimization was
      weaker for women than men. Discussion: Findings suggest that the phenomenon of
      revictimization may occur not only in early and middle adulthood, but also in
      late life. To advance our understanding of victimization across the life course,
      future research on root causes of elder abuse should include histories of child
      abuse.

PMID- 29590469
TI  - Situational and Demographic Factors in the Sudden Growth of Pall Mall, 2002-2014.
AB  - Objective: Pall Mall gained significant brand share in the cigarette market
      between 2002 and 2013. We sought to determine whether demographic shifts occurred
      among the participants reporting Pall Mall as their usual brand during this time
      span. Method: We examined National Survey of Drug Use and Health (NSDUH) data
      from 2002-2014. Demographic characteristics included age, education, ethnicity,
      income, and cigarette use (cigarettes per day, daily/non-daily smoking, and
      nicotine dependence). We also examined RJ Reynolds investor reports and
      shareholder documents to determine the impact of tobacco marketing on the growth
      of Pall Mall. Results: Over 2002-2014, Pall Mall has gained among smokers 26 to
      34 years of age. More Pall Mall smokers in 2014 report higher incomes (over
      $75000), and also report lower scores on measures of cigarette dependence,
      compared to 2002. Pall Mall smokers over time seem to share characteristics of
      premium cigarette brands smokers. Conclusion: The profile of the typical Pall
      Mall smoker has changed as the brand has gained market share. An association
      exists between brand positioning and economic forces, which has contributed to an
      increase in the market share for Pall Mall. Implications: It is well known that
      cigarette marketing drives the sale of tobacco products. The growth in the market
      share of Pall Mall serves as an excellent example to demonstrate how economic
      uncertainty paired with brand positioning and advertising worked together to
      serve as a catalyst for the rapid growth observed for this brand. This paper also
      looked at various demographic changes that occurred among Pall Mall smokers over
      a 12 year period and compared them to smokers of all other cigarette brands. The
      results of this analysis demonstrate the importance of monitoring trends over
      time among cigarette smokers.

PMID- 29590470
TI  - Accuracy of Bioelectrical Impedance Analysis in Estimated Longitudinal Fat-Free
      Mass Changes in Male Army Cadets.
AB  - Introduction: Bioelectrical impedance analysis (BIA) is a practical and rapid
      method for making a longitudinal analysis of changes in body composition.
      However, most BIA validation studies have been performed in a clinical population
      and only at one moment, or point in time (cross-sectional study). The aim of this
      study is to investigate the accuracy of predictive equations based on BIA with
      regard to the changes in fat-free mass (FFM) in Brazilian male army cadets after
      7 mo of military training. The values used were determined using dual-energy X
      ray absorptiometry (DXA) as a reference method. Materials and Methods: The study
      included 310 male Brazilian Army cadets (aged 17-24 yr). FFM was measured using
      eight general predictive BIA equations, with one equation specifically applied to
      this population sample, and the values were compared with results obtained using
      DXA. The student's t-test, adjusted coefficient of determination (R2), standard
      error of estimation (SEE), Lin's approach, and the Bland-Altman test were used to
      determine the accuracy of the predictive BIA equations used to estimate FFM in
      this population and between the two moments (pre- and post-moment). Results: The
      FFM measured using the nine predictive BIA equations, and determined using DXA at
      the post-moment, showed a significant increase when compared with the pre-moment
      (p < 0.05). All nine predictive BIA equations were able to detect FFM changes in
      the army cadets between the two moments in a very similar way to the reference
      method (DXA). However, only the one BIA equation specific to this population
      showed no significant differences in the FFM estimation between DXA at pre- and
      post-moment of military routine. All predictive BIA equations showed large limits
      of agreement using the Bland-Altman approach. Conclusion: The eight general
      predictive BIA equations used in this study were not found to be valid for
      analyzing the FFM changes in the Brazilian male army cadets, after a period of
      approximately 7 mo of military training. Although the BIA equation specific to
      this population is dependent on the amount of FFM, it appears to be a good
      alternative to DXA for assessing FFM in Brazilian male army cadets.

PMID- 29590471
TI  - The challenge of opt-outs from NHS data: a small-area perspective.

PMID- 29590472
TI  - Age and Gender Differences in Social Network Composition and Social Support Among
      Older Rural South Africans: Findings From the HAALSI Study.
AB  - Objectives: Drawing on the "Health and Aging in Africa: A Longitudinal Study of
      an INDEPTH community in South Africa" (HAALSI) baseline survey, we present data
      on older adults' social networks and receipt of social support in rural South
      Africa. We examine how age and gender differences in social network
      characteristics matched with patterns predicted by theories of choice- and
      constraint-based network contraction in older adults. Method: We used regression
      analysis on data for 5,059 South African adults aged 40 and older. Results: Older
      respondents reported fewer important social contacts and less frequent
      communication than their middle-aged peers, largely due to fewer nonkin
      connections. Network size difference between older and younger respondents was
      greater for women than for men. These gender and age differences were explicable
      by much higher levels of widowhood among older women compared to younger women
      and older men. There was no evidence for employment-related network contraction
      or selective retention of emotionally supportive ties. Discussion: Marriage
      related structural constraints impacted on older women's social networks in rural
      South Africa, but did not explain choice-based network contraction. These
      findings suggest that many older women in rural Africa, a growing population, may
      have an unmet need for social support.

PMID- 29590473
TI  - Disability Rating, Age at Death, and Cause of Death in U.S. Veterans with Service
      Connected Conditions.
AB  - Introduction: The association between disability and cause of death in Veterans
      with service-connected disabilities has not been studied. The objective of this
      study was to compare age at death, military service and disability
      characteristics, including disability rating, and cause of death by year of
      birth. We also examined cause of death for specific service-connected conditions.
      Materials and methods: This study used information from the VETSNET file, which
      is a snapshot of selected items from the Veterans Benefits Administration
      corporate database. We also used the National Death Index (NDI) for Veterans
      which is part of the VA Suicide Data Repository. In VETSNET, there were 758,324
      Veterans who had a service-connected condition and died between the years 2004
      and 2014. Using the scrambled social security number to link the two files
      resulted in 605,493 (80%) deceased Veterans. Age at death, sex, and underlying
      cause of death were obtained from the NDI for Veterans and military service
      characteristics and types of disability were acquired from VETSNET. We
      constructed age categories corresponding to period of service; birth years 1938
      and earlier corresponded to Korea and World War II ("oldest"), birth years 1939
      1957 to the Vietnam era ("middle"), and birth years 1958 and later to post
      Vietnam, Gulf War, and the more recent conflicts in Iraq and Afghanistan
      ("youngest"). Results: Sixty-two percent were in the oldest age category, 34% in
      the middle group, and 4% in the youngest one. The overall age at death was 75 +/-
      13 yr. Only 1.6% of decedents were women; among women 25% were in the youngest
      age group, while among men only 4% were in the youngest group. Most decedents
      were enlisted personnel, and 60% served in the U.S. Army. Nearly 61% had a
      disability rating of >50% and for the middle age group 54% had a disability
      rating of 100%. The most common service-connected conditions were tinnitus,
      hearing loss, and post-traumatic stress disorder (PTSD). In the oldest group,
      nearly half of deaths were due to cancer or cardiovascular conditions and <2%
      were due to external causes. In the youngest group, cardiovascular disease and
      cancer accounted for about 1/3 of deaths, whereas external causes or deaths due
      to accidents, suicide, or assault accounted for nearly 33% of deaths. For
      Veterans with service-connected PTSD or major depression; 6.5% of deaths were due
      to external causes whereas for Veterans without these conditions, only 3.1% were
      due to external causes. Conclusion: The finding of premature death due to
      external causes in the youngest age group as well as the finding of higher
      proportions of external causes in those with PTSD or major depression should be
      of great concern to those who care for Veterans.

PMID- 29590475
TI  - Tinnitus and Associated Handicaps in the French Mountain Artillery: Assessment by
      the Tinnitus Handicap Inventory.
AB  - Introduction: Tinnitus and associated handicap related to acoustic trauma
      sequelae have never been assessed in the French artillery. Although impulsive
      noise exposure to firearms and canons are thought to increase prevalence of
      tinnitus among soldiers, recent studies demonstrating this fact are missing.
      Materials and Methods: Here, a representative sample of 389 soldiers from an
      operational mountain artillery regiment was surveyed. Soldiers personally
      concerned by tinnitus were invited to fill in a questionnaire. We assessed
      tinnitus and the associated handicap using a French translation of the Tinnitus
      Handicap Inventory (THI). Questions about attention/concentration problems,
      impaired speech hearing and understanding, sleep disorders, social and familial
      tension, irritability, depression, and tiredness as linked to tinnitus were the
      core of the questionnaire. Results: Soldiers that completed the THI (n = 73, 19%)
      had a mean THI score of 18 +/- 17, this mean score corresponded to a mild
      handicap. At this grade, tinnitus should be easily masked and should not
      interfere with daily activities. The percentage of soldiers concerned by tinnitus
      was slightly higher in the older age class, but there was no significant
      difference of THI scores between the different age classes. The most reported
      handicaps were attention/concentration problems, impaired speech hearing, and
      understanding. Among the THI fillers, eight soldiers (11%) had THI scores >36,
      indicating a moderate to severe handicap. Conclusion: Despite a mild tinnitus
      handicap, the percentage of people concerned by tinnitus in this regiment is
      higher (19%) than that in the estimated percentage of general population of
      European countries (about 10%). It should be of interest to replicate this type
      of study from other regiments and from other countries. Education and good
      fitting of hearing protection for prevention of acoustic trauma sequelae should
      still be encouraged.

PMID- 29590474
TI  - The association of obesity with disease activity, functional ability and quality
      of life in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis
      Study/Early Rheumatoid Arthritis Network UK prospective cohorts.
AB  - Objectives: To examine associations between BMI and disease activity, functional
      ability and quality of life in RA. Methods: Data from two consecutive, similarly
      designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS)
      and the Early RA Network (ERAN). Recruitment figures/median follow-up for the
      ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10
      years), respectively. Standard demographic and clinical variables were recorded
      at baseline and annually. Multilevel piecewise longitudinal models with a change
      point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item
      Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as
      dependent variables. BMI was examined in separate models as both continuous and
      categorical variables (based on World Health Organization definitions) and up to
      5 years from disease onset. Results: BMI data from 2386 newly diagnosed RA
      patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI
      0.21, 0.33). Baseline obesity was associated with a significant reduction in the
      odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2,
      HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients
      obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at
      year 2, but not at year 5, and also associated with significantly higher HAQ and
      SF-36 PCS scores at years 2 and 5. Conclusion: Obesity prevalence is rising in
      early RA and associates with worse disease activity, function and health-related
      quality of life, with a significant negative impact on achieving a low DAS28. The
      data argue strongly for obesity management to become central to treatment
      strategies in RA.

PMID- 29590476
TI  - Thymic plasma cell neoplasm infiltration in Sjogren's syndrome with monoclonal
      gammopathy.

PMID- 29590478
TI  - Probabilistic Category Learning and Striatal Functional Activation in Psychosis
      Risk.
AB  - Background: Psychosis risk is associated with striatal dysfunction, including a
      previous behavioral study that found that psychosis risk is associated with
      impaired performance on a probabilistic category learning task (PCLT; ie, the
      Weather Prediction Task), a task strongly associated with striatal activation.
      The current study examined whether psychosis risk based on symptom levels was
      associated with both poor behavioral performance and task-related physiological
      dysfunction in specific regions of the striatum while performing the PCLT.
      Methods: There were 2 groups of participants: psychosis risk (n = 21) who had
      both (a) extreme levels of self-reported psychotic-like beliefs and experiences
      and (b) interview-rated current attenuated psychotic symptoms (APS); and a
      comparison group (n = 20) who had average levels of self-reported psychotic-like
      beliefs and experiences. Participants completed the PCLT during fMRI scanning.
      Results: The current research replicated previous work finding behavioral PCLT
      deficits at the end of the task in psychosis risk. Furthermore, as expected, the
      psychosis risk group exhibited decreased striatal activation on the task,
      especially in the associative striatum. The psychosis risk group also displayed
      decreased activation in a range of cortical regions connected to the associative
      striatum. In contrast, the psychosis risk group exhibited greater activation
      predominantly in cortical regions not connected to the associative striatum.
      Conclusions: Psychosis risk was associated with both behavioral and striatal
      dysfunction during performance on the PCLT, suggesting that behavioral and
      imaging measures using this task could be a marker for psychosis risk.

PMID- 29590477
TI  - RNA-splicing factor SART3 regulates translesion DNA synthesis.
AB  - Translesion DNA synthesis (TLS) is one mode of DNA damage tolerance that uses
      specialized DNA polymerases to replicate damaged DNA. DNA polymerase eta (Poleta)
      is well known to facilitate TLS across ultraviolet (UV) irradiation and mutations
      in POLH are implicated in skin carcinogenesis. However, the basis for recruitment
      of Poleta to stalled replication forks is not completely understood. In this
      study, we used an affinity purification approach to isolate a Poleta-containing
      complex and have identified SART3, a pre-mRNA splicing factor, as a critical
      regulator to modulate the recruitment of Poleta and its partner RAD18 after UV
      exposure. We show that SART3 interacts with Poleta and RAD18 via its C-terminus.
      Moreover, SART3 can form homodimers to promote the Poleta/RAD18 interaction and
      PCNA monoubiquitination, a key event in TLS. Depletion of SART3 also impairs UV
      induced single-stranded DNA (ssDNA) generation and RPA focus formation, resulting
      in an impaired Poleta recruitment and a higher mutation frequency and
      hypersensitivity after UV treatment. Notably, we found that several SART3
      missense mutations in cancer samples lessen its stimulatory effect on PCNA
      monoubiquitination. Collectively, our findings establish SART3 as a novel
      Poleta/RAD18 association regulator that protects cells from UV-induced DNA
      damage, which functions in a RNA binding-independent fashion.

PMID- 29590479
TI  - Stakeholder perspectives on costs and resource expenditures: tools for addressing
      economic issues most relevant to patients, providers, and clinics.
AB  - Cost and other resources required are often primary considerations in whether a
      potential program or policy will be adopted or implemented and an important
      element in determining value. However, few economic analyses are conducted from
      the perspective of patient/family or small-scale stakeholders such as local
      clinics. We outline and discuss alternative cost assessment and resource
      expenditures options from the perspective of these small, proximal stakeholders.
      The perspective of these persons differs from larger societal or health plan
      perspectives, and often differs across individuals in terms of what they value
      and the types of expenditures about which they are concerned. We discuss key
      features of the perspectives of patients, health care clinics, and local leaders,
      and present brief examples and sample templates for collection of
      consumer/stakeholder relevant cost and return on investment issues. These tools
      can be used prospectively and iteratively during program planning, intervention
      delivery, summative analysis, and preparation for dissemination stages. There is
      an important need for this type of feasible, pragmatic, rapid, and iterative cost
      and resource expenditure analysis directly relevant to patients/families, small
      local stakeholders and their organizations. Future research on and use of these
      approaches is recommended.

PMID- 29590481
TI  - Letter: Navigation-Linked Heads-Up Display in Intracranial Surgery: Early
      Experience.

PMID- 29590480
TI  - Anatomic predictors of response and mechanism of action of upper airway
      stimulation therapy in patients with obstructive sleep apnea.
AB  - Study Objectives: Upper airway stimulation has been shown to be an effective
      treatment for some patients with obstructive sleep apnea. However, the mechanism
      by which hypoglossal nerve stimulation increases upper airway caliber is not
      clear. Therefore, the objective of this study was to identify the mechanism of
      action of upper airway stimulation. We hypothesized that, with upper airway
      stimulation, responders would show greater airway opening in the retroglossal
      (base of the tongue) region, greater hyoid movement toward the mandible, and
      greater anterior motion in the posterior, inferior region of the tongue compared
      with nonresponders. Methods: Seven participants with obstructive sleep apnea who
      had been successfully treated with upper airway stimulation (responders) and six
      participants who were not successfully treated (nonresponders) underwent computed
      tomography imaging during wakefulness with and without hypoglossal nerve
      stimulation. Responders reduced their apnea-hypopnea index (AHI) by 22.63 +/-
      6.54 events per hour, whereas nonresponders had no change in their AHI (0.17 +/-
      14.04 events per hour). We examined differences in upper airway caliber, the
      volume of the upper airway soft tissue structures, craniofacial relationships,
      and centroid tongue and soft palate movement between responders and nonresponders
      with and without hypoglossal nerve stimulation. Results: Our data indicate that
      compared with nonresponders, responders had a smaller baseline soft palate volume
      and, with stimulation, had (1) a greater increase in retroglossal airway size;
      (2) increased shortening of the mandible-hyoid distance; and (3) greater anterior
      displacement of the tongue. Conclusions: These results suggest that smaller soft
      palate volumes at baseline and greater tongue movement anteriorly with
      stimulation improve the response to upper airway stimulation.

PMID- 29590482
TI  - Using Neuroscience to Inform Tobacco Control Policy.
AB  - Background and Aims: Techniques employed in the field of neuroscience, such as
      eye-tracking, electroencephalography, and functional magnetic resonance imaging,
      have been important in informing our understanding of the cognitive mechanisms
      underlying tobacco smoking. These techniques are now increasingly being used to
      investigate the likely impact of tobacco control measures. Methods: In this
      narrative review, we outline the value of these methodological approaches in
      answering policy relevant tobacco control research questions, with a particular
      focus on their use in examining the impact of standardised cigarette packaging
      and health warnings. We also examine the limitations of these methodologies and
      provide examples of how these technologies can be used to answer other policy
      relevant questions. Results: We argue that neuroscience techniques can provide
      more objective evidence of the impacts of policy measures, allow investigation
      where it is not possible to conduct behavioural manipulations and facilitate a
      deeper understanding of the cognitive mechanisms underlying the impacts of
      tobacco control policies such as standardised packaging, health warnings, point
      of sale displays and mass media campaigns. Conclusions: Rather than replacing
      more traditional methods of examining tobacco control measures, such as
      observational experiments, surveys and questionnaires, neuroscience techniques
      can complement and extend these methods. Implications: Neuroscience techniques
      can provide more objective evidence of the impacts of policy measures, allow
      investigation where it is not possible to conduct behavioural manipulations and
      facilitate a deeper understanding of the cognitive mechanisms underlying the
      impacts of tobacco control policies. Rather than replacing more traditional
      methods of examining tobacco control measures, such as observational experiments,
      surveys and questionnaires, neuroscience techniques can complement and extend
      these methods.

PMID- 29590483
TI  - Building Capacity for Complementary and Integrative Medicine Through a Large,
      Cross-Agency, Acupuncture Training Program: Lessons Learned from a Military
      Health System and Veterans Health Administration Joint Initiative Project.
AB  - Introduction: Complementary and integrative medicine (CIM) use in the USA
      continues to expand, including within the Military Health System (MHS) and
      Veterans Health Administration (VHA). To mitigate the opioid crisis and provide
      additional non-pharmacological pain management options, a large cross-agency
      collaborative project sought to develop and implement a systems-wide curriculum,
      entitled Acupuncture Training Across Clinical Settings (ATACS). Materials and
      Methods: ATACS curriculum content and structure were created and refined over the
      course of the project in response to consultations with Subject Matter Experts
      and provider feedback. Course content was developed to be applicable to the MHS
      and VHA environments and training was open to many types of providers. Training
      included a 4-hr didactic and "hands on" clinical training program focused on a
      single auricular acupuncture protocol, Battlefield Acupuncture. Trainee learning
      and skills proficiency were evaluated by trainer-observation and written
      examination. Immediately following training, providers completed an evaluation
      survey on their ATACS experience. One month later, they were asked to complete
      another survey regarding their auricular acupuncture use and barriers to use. The
      present evaluation describes the ATACS curriculum, faculty and trainee
      characteristics, as well as trainee and program developer perspectives. Results:
      Over the course of a 19-mo period, 2,712 providers completed the in-person, 4-hr
      didactic and hands-on clinical training session. Due to the increasing requests
      for training, additional ATACS faculty were trained. Overall, 113 providers were
      approved to be training faculty. Responses from the trainee surveys indicated
      high satisfaction with the ATACS training program and illuminated several
      challenges to using auricular acupuncture with patients. The most common reported
      barrier to using auricular acupuncture was the lack of obtaining privileges to
      administer auricular acupuncture within clinical practice. Conclusion: The ATACS
      program provided a foundational template to increase CIM across the MHS and VHA.
      The lessons learned in the program's implementation will aid future CIM training
      programs and improve program evaluations. Future work is needed to determine the
      most efficient means of improving CIM credentialing and privileging procedures,
      standardizing and adopting uniform CIM EHR codes and documentation, and examining
      the effectiveness of CIM techniques in real-world settings.

PMID- 29590484
TI  - Calcium pyrophosphate deposition disease induced sacroiliitis.

PMID- 29590485
TI  - Changing national trends in sleep duration: did we make America sleep again?

PMID- 29590486
TI  - Age, burnout and physical and psychological work ability among nurses.
AB  - Background: The ageing of the US labour force highlights the need to examine
      older adults' physical and psychological ability to work, under varying levels of
      occupational burnout. Aims: To examine how age and burnout interact in predicting
      physical and psychological work ability. Methods: Using a cohort of actively
      working nurses, we assessed factors on the Work Ability Index at 12-month follow
      up and determined how these were related to age and exhaustion-related burnout at
      baseline. Results: The study group consisted of 402 nurses aged 25-67 (mean =
      41.7). Results indicated age by burnout interactions in which decrements in
      physical work ability with greater age were observed at all but the lowest level
      of burnout (1.5 SD below mean: beta = -0.14, 95% CI -0.36, 0.07; 1 SD below: beta
      = -0.23, 95% CI -0.39, -0.06; mean: beta = -0.39, 95% CI -0.50, -0.29; 1 SD
      above: beta = -0.56, 95% CI -0.70, -0.42; 1.5 SD above: beta = -0.64, 95% CI 
      0.83, -0.46). In contrast, we observed decrements in psychological work ability
      with age at higher levels of burnout only (1 SD above: beta = -0.20, 95% CI 
      0.35, -0.05; 1.5 SD above: beta = -0.30, 95% CI -0.49, -0.11); at lower levels of
      burnout, older age was associated with improvements in this (1 SD below: beta =
      0.19, 95% CI 0.03, 0.35; 1.5 SD below: beta = 0.29, 95% CI 0.08, 0.50).
      Conclusions: Findings indicated physical and psychological dimensions of work
      ability that differed by age and occupational burnout. This emphasizes the need
      for interventions to reduce burnout and to address age-related strengths and
      vulnerabilities relating to physical and psychological work ability.

PMID- 29590487
TI  - Psychological Flexibility and Set-Shifting Among Veterans Participating in a Yoga
      Program: A Pilot Study.
AB  - Introduction: Trauma-focused psychotherapies do not meet the needs of all
      veterans. Yoga shows some potential in reducing stress and perhaps even PTSD in
      veterans, although little is understood about the mechanisms of action. This
      study identifies preliminary correlates of change in PTSD and perceived stress
      for veterans participating in yoga. Materials and methods: Nine veterans (seven
      males and two females) were recruited from an existing clinical yoga program and
      observed over 16 wk. Severity of PTSD symptoms (PCL-5) and perceived stress (PSS
      10) were collected at baseline and weeks 4, 6, 8, and 16. Psychological
      flexibility (AAQ-II) and set-shifting (ratio of trail making test A to B) were
      collected at baseline and at week 6. Subjects attended yoga sessions freely,
      ranging from 1 to 23 classes over the 16 weeks. The Stanford University
      Institutional Review Board approved this research protocol. Results: Self
      reported PTSD symptoms significantly reduced while perceived stress did not.
      Lower baseline set-shifting predicted greater improvements in PTSD between
      baseline and 4 weeks; early improvements in set-shifting predicted overall
      reduction in PTSD. Greater psychological flexibility was associated with lower
      PTSD and perceived stress; more yoga practice, before and during the study, was
      associated with greater psychological flexibility. Other predictors were not
      supported. Conclusions: In a small uncontrolled sample, psychological flexibility
      and set-shifting predicted changes in PTSD symptoms in veterans participating in
      a clinical yoga program, which supports findings from prior research. Future
      research should include an active comparison group and record frequency of yoga
      practiced outside formal sessions.

PMID- 29590488
TI  - 2018 Toxicological Sciences Paper of the Year: Assessing Fibrogenesis Using 3D
      Printed Liver Tissues.

PMID- 29590489
TI  - Diagnostic challenges in Mycobacteria chimaera infection.

PMID- 29590490
TI  - Fatal invasive otitis with skull base osteomyelitis caused by Saksenaea
      vasiformis.

PMID- 29590491
TI  - Derivation of Permitted Daily Exposure for Flutamide.

PMID- 29590492
TI  - An end-to-end framework for real-time automatic sleep stage classification.
AB  - Sleep staging is a fundamental but time consuming process in any sleep
      laboratory. To greatly speed up sleep staging without compromising accuracy, we
      developed a novel framework for performing real-time automatic sleep stage
      classification. The client-server architecture adopted here provides an end-to
      end solution for anonymizing and efficiently transporting polysomnography data
      from the client to the server and for receiving sleep stages in an interoperable
      fashion. The framework intelligently partitions the sleep staging task between
      the client and server in a way that multiple low-end clients can work with one
      server, and can be deployed both locally as well as over the cloud. The framework
      was tested on four datasets comprising ~1700 polysomnography records (~12000 hr
      of recordings) collected from adolescents, young, and old adults, involving
      healthy persons as well as those with medical conditions. We used two independent
      validation datasets: one comprising patients from a sleep disorders clinic and
      the other incorporating patients with Parkinson's disease. Using this system, an
      entire night's sleep was staged with an accuracy on par with expert human scorers
      but much faster (~5 s compared with 30-60 min). To illustrate the utility of such
      real-time sleep staging, we used it to facilitate the automatic delivery of
      acoustic stimuli at targeted phase of slow-sleep oscillations to enhance slow
      wave sleep.

PMID- 29590493
TI  - Longitudinal Twin Study of Subjective Health: Differences in Genetic and
      Environmental Components of Variance Across Age and Sex.
AB  - Objective: The current analysis examines sex differences in longitudinal changes
      in genetic and environmental influences on three measures of subjective health.
      Method: Sample includes 7372 twins (mean intake age = 73.22) with up to 8 waves
      of measurement (mean = 3.1). Three subjective health (SH) items were included:
      general self-rated health (SRH), health compared to age peers (COMP), and impact
      of health on activities (ACT) which previous research shows capture different
      frames of reference. Results: Latent growth curve modeling indicated significant
      differences across gender and frame of reference in trajectories of change with
      age and in genetic and environmental contributions to change. Men have higher
      mean scores on all three SH measures, indicating better SH, but there were no sex
      differences in pattern of change with age. Accelerating declines with age were
      found for SRH and ACT, whereas COMP improved with age. Results indicated more
      genetic variance for women than men, but declining genetic variance for both
      after age 70. Increasing shared environmental variance with increasing age was
      also found for both sexes. Discussion: As aging triggers a re-evaluation of the
      meaning of "good health," physical aspects of health may become less important
      and shared cultural conceptions of health may become more relevant. This change
      in conceptions of good health may reflect both aging and the change in
      composition of the elderly population as a result of selective survival.

PMID- 29590494
TI  - Endocrinopathies and renal outcomes in lithium therapy: impact of lithium
      toxicity.
AB  - Background: Lithium is the mainstay of treatment for bipolar disorder, mania and
      an augmentation therapy in patients with treatment resistant depression. It has a
      narrow therapeutic index, with recognized adverse multi-system and endocrine side
      effects. Aim: To assess the impact of lithium therapy, in particular lithium
      toxicity, on the development of endocrine and renal disorders in a cohort of
      patients in a single tertiary referral centre in Ireland. Study design: A
      retrospective analysis was performed of the prevalence of lithium toxicity and
      renal, thyroid and parathyroid dysfunction in our study population. Methods: We
      collected laboratory data from the Clinical Chemistry department of the Adelaide
      and Meath Hospital incorporating the National Children's Hospital (AMNCH),
      Dublin, Ireland. Our study population included all patients who had at least one
      serum lithium measurement from January 1st 2000 to December 31st 2014 inclusive.
      Results: A total of 580 patients were included in the study. Among our study
      group, 70 patients (12.1%) had 1 toxic lithium measurement (lithium level >1.2
      mmol/l). 27.8% (n > 161) of patients developed stage 3 Chronic kidney Disease
      (CKD) or higher, which was commoner in those patients who developed toxic lithium
      levels (P < 0.0001) and in those who developed hypernatraemia (P > 0.0001). 16.2%
      of patients (n > 94) had one serum sodium >145 mmol/l during follow up. 60
      patients(10.3%) had a TSH >10 mU/l, while complete suppression of TSH (<0.05
      mU/l) was observed in 22 patients (3.8%) during follow-up. 4% (n > 37) of the
      study population had >=1 serum corrected calcium level > 2.55 mmol/l, and 4
      patients had biochemical confirmation of primary hyperparathyroidism but PTH
      levels were only performed in 2.8% (n > 16) of the studypopulation. Conclusion:
      Stage 3 CKD is common in patients receiving lithium therapy. Lithium toxicity is
      associated with CKD and hypernatraemia. Thyroid dysfunction and hypercalcaemia
      are common in patients receiving lithium therapy. Patients receiving lithium
      therapy require surveillance of renal, thyroid and bone biochemistry.

PMID- 29590496
TI  - Quality of life: why most doctors don't care?

PMID- 29590495
TI  - Prediction of Drug-Induced Hepatotoxicity Using Long-Term Stable Primary Hepatic
      3D Spheroid Cultures in Chemically Defined Conditions.
AB  - High failure rates of drug candidates in the clinics, restricted-use warnings as
      well as withdrawals of drugs in postmarketing stages are of substantial concern
      for the pharmaceutical industry and drug-induced liver injury (DILI) constitutes
      one of the most frequent reasons for such safety failures. Importantly, as DILI
      cannot be accurately predicted using animal models, animal safety tests are
      commonly complemented with assessments in human in vitro systems. 3D spheroid
      cultures of primary human hepatocytes in chemically defined conditions, hereafter
      termed CD-spheroids, have recently emerged as a microphysiological model system
      in which hepatocytes retain their molecular phenotypes and hepatic functions for
      multiple weeks in culture. However, their predictive power for the detection of
      hepatotoxic liabilities has not been systematically assessed. Therefore, we here
      evaluated the hepatotoxicity of 123 drugs with or without direct implication in
      clinical DILI events. Importantly, using ATP quantifications as the single
      endpoint, the model accurately distinguished between hepatotoxic and nontoxic
      structural analogues and exceeded both sensitivity and specificity of all
      previously published in vitro assays at substantially lower exposure levels,
      successfully detecting 69% of all hepatotoxic compounds without producing any
      false positive results (100% specificity). Furthermore, the platform supports the
      culture of spheroids of primary hepatocytes from preclinical animal models,
      thereby allowing the identification of animal-specific toxicity events. We
      anticipate that CD-spheroids represent a powerful and versatile tool in drug
      discovery and preclinical drug development that can reliably flag hepatotoxic
      drug candidates and provide guidance for the selection of the most suitable
      animal models.

PMID- 29590497
TI  - Chronic idiopathic erythroderma of elderly men is an independent entity that has
      a distinct TARC/IgE profile from adult atopic dermatitis.
AB  - BACKGROUND: Although there are several diseases that cause erythroderma, patients
      are often encountered with erythroderma of unknown cause which persists for a
      long time. The aim of this study was to characterize this chronic idiopathic
      erythroderma (CIE). METHODS: Adult patients with CIE, atopic dermatitis (AD),
      psoriatic erythroderma (PsE), or generalized drug eruption (DE), who visited
      Fukuoka University Hospital Dermatology Department from 2010 to 2015, were
      enrolled. Their clinical and laboratory data were extracted from the patient
      database. CIE was defined as erythroderma without any apparent cause and lasting
      more than 3 months. RESULTS: Twenty-three CIE, 82 AD, 39 psoriatic erythroderma,
      and 99 drug eruption cases were enrolled. The mean age of CIE patients was 74.7
      +/- 8.8, and the male : female ratio was 21 : 2. Laboratory data for CIE and AD
      were similar, but serum levels of thymus and activation-regulated chemokine
      (TARC), a T-helper (Th) 2 cytokine, in the CIE group were significantly more
      elevated than in the AD group. Conversely, serum immunoglobulin (Ig) E levels
      were significantly lower in CIE patients compared with the atopic dermatitis
      group, and the ROC curve of the TARC/IgE ratio (7.24) provided efficient
      differentiation of the CIE group from AD patients. About PsE and DE, significant
      elevation of C-reactive protein was observed. Aspartate aminotransferase and
      alanine aminotransferase were also elevated in DE. CONCLUSIONS: Chronic
      idiopathic erythroderma is an independent condition which is likely to occur in
      elderly men. Immunity is shifted to the Th2 type in CIE; however, the mechanism
      may differ from that of atopic dermatitis.

PMID- 29590498
TI  - Skin cancer risk and the use of UV nail lamps.

PMID- 29590500
TI  - Educational Opportunities.

PMID- 29590503
TI  - Did You Know?

PMID- 29590504
TI  - American Nurses Association revamps campaigns to support healthy nurses.

PMID- 29590505
TI  - Total abdominal hysterectomy.

PMID- 29590507
TI  - Evaluating perioperative nurses' health, safety, and wellness.

PMID- 29590508
TI  - Surgical innovations: the bionic eye implant.

PMID- 29590511
TI  - Abortion Bans, Doctors, and the Criminalization of Patients.
AB  - January 2018, the American College of Obstetrics and Gynecology issued a position
      statement opposing the punishment of women for self-induced abortion. To those
      unfamiliar with emerging trends in abortion in the United States and worldwide,
      the need for the declaration might not be apparent. Several studies suggest that
      self-induced abortion is on the rise in the United States. Simultaneously,
      prosecutions of pregnant women for behavior thought to harm the fetus are
      increasing. The ACOG statement responds to both trends by urging doctors to honor
      the integrity and confidentiality inherent in the doctor-patient relationship.
      Seen in the context of the larger battle over legal abortion, the statement has
      far broader implications. By acknowledging the role doctors play in enforcing
      pregnancy-related crimes, the ACOG position statement wisely anticipates the ways
      in which doctors will be implicated should access to legal abortion be further
      restricted. To understand the need for the ACOG directive, you must first
      understand that the story of what will happen if abortion becomes a crime in the
      United States is not to be found in history books; it is staring at us across our
      southern border.

PMID- 29590512
TI  - Progress: Its Glories and Pitfalls.
AB  - Steven Pinker, a cognitive psychologist and linguist at Harvard and a savant of
      big ideas, is one of the latest to take on the idea of progress. He does it under
      the aegis of "enlightenment," which comes down to a kind of holy trinity of
      reason, science, and humanism. His new book, Enlightenment Now: The Case for
      Reason, Science, Humanism, and Progress, is ambitious and cantankerous and heady
      with hope. On the whole, Pinker makes a good case for the benefits of progress,
      but with an overdose of feel-good prose. His greatest failure comes in
      exaggerating the threats to science and in avoiding some problems altogether. He
      ignores its complexity, its shadows, its creation of new problems raised by its
      solutions to old ones. Pinker has a particular animus against bioethics, and he
      misses what has been, I would argue, at the heart of bioethics from its beginning
      fifty or so years ago. Bioethics was prompted by a new class of medical dilemmas
      that require a difficult balancing of harms and benefits. Most of them are still
      with us, and most of them are the result of the progress of postwar medical
      research and fast-changing clinical practices.

PMID- 29590513
TI  - Genome "Surgery"?
AB  - When Kai Kupferschmidt writes about CRISPR-based gene editing in German, he faces
      an obstacle: there's no exact translation for "editing" that has the same
      connotations as it has in English. Instead, as he explained last fall at The
      Hastings Center's preconference symposium on new genetic technologies at the
      World Conference of Science Journalists, he draws on a variety of phrases,
      including "genome surgery," which conveys precision in Kupferschmidt's
      assessment, and "gene scissors," which communicates CRISPR's mechanistic nature.
      But in any language, explaining CRISPR is difficult. It's a challenge I face at
      The Hastings Center, where I write about biotechnology for a public audience.

PMID- 29590514
TI  - One Ventilator Too Few?
AB  - Sometimes it's better to be lucky than good. As new blood filled our young
      patient's veins, her breathing became regular and her pulse full. She was so far
      gone I would not have expected her to recover consciousness for a day, if at all,
      but within an hour, she began to wake up. We removed the breathing tube a couple
      of hours later- no ventilator ever needed. As life-sustaining technology becomes
      more widely available in fortunate parts of the developing world, benefits come
      with complications. The temptation is to focus on the thing-the ventilator itself
      as the crucial element and press to buy more, mistaking the problem for one of
      resource scarcity only. But we need a culturally relevant ethical framework to
      guide the use and withdrawal of ventilators and similar life-sustaining tools.
      Resource scarcity is only part of the problem. Buying additional ventilators only
      defers allocation decisions and entirely fails to address end-of-life suffering.
      It is unsustainable in Rwanda; it is a dubious solution anywhere. The intangible
      need for an ethical framework hides beneath apparent scarcity and, when this need
      is not addressed and luck runs out, one salvageable patient can die for want of a
      ventilator that serves only to prolong the suffering of another.

PMID- 29590515
TI  - Fetal Medicine and the Pregnant Woman.
AB  - In coming decades, fetal medicine may become a routine part of reproductive care.
      The measures pregnant women now take to protect fetal health are largely generic,
      like restricting their diets and using supplements. Relatively few interventions
      are based on specific conditions revealed by ultrasound or genetic testing. A
      recent finding, though, may herald a dramatic rise in "personalized" fetal
      medicine: certain drugs already approved by the Food and Drug Administration can
      apparently boost neural growth in fetuses with Down syndrome, improving cognitive
      functioning in the future child. Many more condition-specific findings are likely
      in the near future. But as commentators have frequently observed about prenatal
      testing, technologies that appear to increase reproductive options also
      complicate and constrain them.

PMID- 29590516
TI  - Organ Transplantation and the Uniform Anatomical Gift Act: A Fifty-Year
      Perspective.
AB  - Fifty years ago this summer, the Uniform Anatomical Gift Act was adopted by the
      National Conference of Commissioners on Uniform State Laws and approved by the
      American Bar Association. The UAGA has provided a sound and stable legal platform
      on which to base an effective nationwide organ donation system. The cardinal
      principles of altruism, autonomy, and public trust are still important. At a time
      when confidence and trust in our government and many private institutions has
      declined, maintaining trust and confidence in our health care system and its
      commitment to "first, do no harm" has never been more important. Any policies
      that override these core ethical principles could cause irreparable damage to the
      public's faith in our transplant system. While progress has been made to increase
      organ registration and the number of organs transplanted, much more must be done
      to realize the potential of life-saving therapy without jeopardizing ethical
      principles.

PMID- 29590518
TI  - Financial Conflicts of Interest at FDA Drug Advisory Committee Meetings.
AB  - The U.S. Food and Drug Administration's drug advisory committees provide expert
      assessments of the safety and efficacy of new therapies considered for approval.
      A committee hears from a variety of speakers, from six groups, including voting
      members of the committee, FDA staff members, employees of the pharmaceutical
      company seeking approval of a therapy, patient and consumer representatives,
      expert speakers invited by the company, and public participants. The committees
      convene at the request of the FDA when the risks and harms of novel products are
      not immediately clear, and their final decisions carry significant weight, as
      most therapies that receive advisory committee approval are subsequently approved
      by the FDA. In recent years, across a series of diverse publications, the
      financial conflicts of interest of each category of participants in the meetings
      have been investigated. Here, we summarize these findings and their ethical
      implications, focusing on the FDA Oncologic Drugs Advisory Committee, and we
      suggest ways to move toward more transparent and impartial advisory committee
      meetings.

PMID- 29590519
TI  - Nudge or Grudge? Choice Architecture and Parental Decision-Making.
AB  - Richard Thaler and Cass Sunstein define a nudge as "any aspect of the choice
      architecture that alters people's behavior in a predictable way without
      forbidding any options or significantly changing their economic incentives." Much
      has been written about the ethics of nudging competent adult patients. Less has
      been written about the ethics of nudging surrogates' decision-making and how the
      ethical considerations and arguments in that context might differ. Even less has
      been written about nudging surrogate decision-making in the context of
      pediatrics, despite fundamental differences that exist between the pediatric and
      adult contexts. Yet, as the field of behavioral economics matures and its
      insights become more established and well-known, nudges will become more crafted,
      sophisticated, intentional, and targeted. Thus, the time is now for reflection
      and ethical analysis regarding the appropriateness of nudges in pediatrics. We
      argue that there is an even stronger ethical justification for nudging in
      parental decision-making than with competent adult patients deciding for
      themselves. We give three main reasons in support of this: (1) child patients do
      not have autonomy that can be violated (a concern with some nudges), and nudging
      need not violate parental decision-making authority; (2) nudging can help fulfill
      pediatric clinicians' obligations to ensure parental decisions are in the child's
      interests, particularly in contexts where there is high certainty that a
      recommended intervention is low risk and of high benefit; and (3) nudging can
      relieve parents' decisional burden regarding what is best for their child,
      particularly with decisions that have implications for public health.

PMID- 29590520
TI  - Mass Shootings, Mental Illness, and Gun Control.
AB  - In the wake of the Stoneman Douglas School shooting, Republican and Democratic
      leaders-like the American electorate they represent-remain sharply divided in
      their responses to gun violence. They are united in their condemnation of these
      mass shootings, but they disagree about whether stricter or looser gun control
      laws are the answer. Those on the right side of the political aisle suggest that
      the issue is one of mental illness rather than gun control. Conversely, those who
      are more liberal or progressive in their political learnings are quick to condemn
      attempts to reframe the issue of mass shootings as a mental health problem. Both
      sides are wrong. Mass shootings are indeed partially a mental health problem,
      albeit one poorly addressed by our current laws and policies. But the solution to
      mass shootings also needs to consider strategies that may reduce gun violence in
      general.

PMID- 29590521
TI  - The Right to Know: A Revised Standard for Reporting Incidental Findings.
AB  - During the course of biomedical research, researchers sometimes obtain
      information on participants that is outside the aim of the study but may
      nonetheless be relevant to the participants. These incidental findings, as they
      are known, have been the focus of a substantial amount of discussion in the
      bioethics literature, and a consensus has begun to emerge about what researchers
      should do in light of the possibility of incidental findings. A consensus,
      however, is not necessarily correct. In this article, we address the common view
      that reporting of incidental findings should be based primarily on the
      possibility of medical benefit, factoring in the findings' validity, clinical
      actionability, and significance to health or reproduction. While such medical
      beneficence should not be discarded, the need to give proper attention to
      participants' autonomy, privacy, and interests (especially considering discussion
      of participants' right not to know) suggests an alternative standard for when to
      report incidental findings: even if they are of no direct medical benefit,
      incidental findings should be reported based on the extent to which the
      participant can be expected to comprehend the information. We will offer a
      preliminary defense of this alternative as best respecting participants' autonomy
      and privacy and promoting their interests. However, we acknowledge that the
      standard would face significant practical barriers, and these barriers lead us to
      propose a metaconsent addendum that would allow subjects to essentially waive the
      comprehension standard when resource or other constraints make meeting it
      impracticable.

PMID- 29590522
TI  - Bioethics and Science.
AB  - Bioethics comes in for furious criticism in Stephen Pinker's new book,
      Enlightenment Now. Pinker argues that scientists are making human lives better
      and better, and that lives would get still better even faster if bioethicists did
      not use ideas like informed consent, dignity, sacredness, and social justice to
      hobble the scientists. Daniel Callahan, a cofounder of The Hastings Center and
      arguably of bioethics, is perhaps the best living embodiment of a bioethicist who
      has written about medical progress, and the March-April 2018 issue of the
      Hastings Center Report turns to him for a review of Pinker's book. In his essay,
      Callahan describes bioethics as guiding science, addressing problems generated by
      scientific developments and attempting to head off possible problems, rather than
      as broadly opposing science. That description of bioethics serves as well as
      anything to convey the flavor of much of this issue of the Report.

PMID- 29590523
TI  - Long-term follow-up comparison of two different bi-layer dermal substitutes in
      tissue regeneration: Clinical outcomes and histological findings.
AB  - Double layer dermal substitute (DS) consist of a 3-dimensional collagen
      structures and a superficial silicon layer that are positioned within the defect
      provide to promote tissue regeneration in skin wounds. DS often have unique
      physical characteristics due to differences in manufacturing techniques. The aim
      of this study is the clinical and histological comparison of Nevelia and Integra
      double layer DSs in patients with post-traumatic injury wounds. Thirty patients
      with post-traumatic wounds localised on the inferior limbs were randomised in 2
      groups Nevelia or Integra, followed by autologous dermal epidermal graft (DEG).
      Clinical results were evaluated through the healing time; Manchester Scar Scale
      (MSS) and Visual Analog Scale (VAS) at 1, 2, and 3 weeks and after 1 and 3 years.
      Histological and immunohistochemical evaluation were performed at 0, 2, and 3
      weeks. The difference in healing time between groups (P = .467, log-rank test),
      pain and self-estimation was not statistically significant after 35, 42, and 49
      days and at 1-year follow up. Histological data showed evident healing of wound
      after 2 weeks compared with preoperative with both DSs. At 3 weeks
      reepithelialisation and dermal regeneration were evident with both substitutes;
      however Nevelia showed early regenerative properties in terms of epidermal
      proliferation and dermal renewal compared with Integra. Nevelia showed also a
      more evident angiogenesis vs Integra evaluated as alpha-SMA immunohistochemistry.
      Differences in the MSS score were statistically significant at 3 years follow up
      in favour of Nevelia group (P = .001). At long-term follow up, Nevelia showed a
      better clinical outcome measured as MSS score vs Integra measured as MSS.
      Histological and immunohistochemistry data showed that Nevelia allows faster
      neoangiogenesis and tissue regeneration with neoformed tissue architecture closer
      to the physiology of the skin.

PMID- 29590524
TI  - [Neuroimaging studies of depression: Current status and future direction.]
AB  - Recent advances in neuroimaging studies enable us to measure brain function non
      invasively. Over the past several decades, neuroimaging measurement has been
      substantially applied to elucidate the neurobiological mechanisms underlying
      major depressive disorder (MDD). Since MDD is a wide spectrum which consists of
      various symptoms such as low mood or loss of interest and is considered to affect
      a biologically het- erogeneous population, we have not yet elucidated the
      biological underpinnings of MDD. It seems to be more promising to consider MDD as
      an integral network abnormality instead of deficits in specific brain regions or
      neurotransmitters. We firstly provide a comprehensive review of the extant
      neuroimaging literature including structural and functional magnetic resonance
      imaging, magnetic resonance spectroscopy, single pho- ton emission computed
      tomography, and positron emission tomography studies. Then we show our
      neuroimaging studies for MDD toward po- tential application as a biomarker for
      diagnosis and treatment. We believe it will facilitate the development, of a more
      integrative model of neural dysfunction in MDD.

PMID- 29590525
TI  - Interfacial Engineering of Nanoporous Architectures in Ga2O3 Film toward Self
      Aligned Tubular Nanostructure with an Enhanced Photocatalytic Activity on Water
      Splitting.
AB  - The present work demonstrates the formation of self-aligned nanoporous
      architecture of gallium oxide by anodization of gallium metal film controlled at 
      15  degrees C in aqueous electrolyte consisting of phosphoric acid. SEM
      examination of the anodized film reveals that by adding ethylene glycol to the
      electrolyte and optimizing the ratio of phosphoric acid and water, chemical
      etching at the oxide/electrolyte interfaces can be controlled, leading to the
      formation of aligned nanotubular oxide structures with closed bottom. XPS
      analysis confirms the chemical composition of the oxide film as Ga2O3. Further,
      XRD and SAED examination reveals that the as-synthesized nanotubular structure is
      amorphous, and can be crystallized to beta-Ga2O3 phase by annealing the film at
      600  degrees C. The nanotubular structured film, when used as photoanode for
      photoelectrochemical splitting of water, achieved a higher photocurrent of about
      two folds than that of the nanoporous film, demonstrating the rewarding effect of
      the nanotubular structure. In addition, the work also demonstrates the formation
      of highly organized nonporous Ga2O3 structure on a nonconducting glass substrate
      coated with thin film of Ga-metal, highlighting that the current approach can be
      extended for the formation of self-organized nanoporous Ga2O3 thin film even on
      nonconducting flexible substrates.

PMID- 29590526
TI  - Hydrogen-Bonding-Driven 3D Supramolecular Assembly of Peptidomimetic Zipper.
AB  - Hydrogen-bonding-driven three-dimensional (3D) assembly of a peptidomimetic
      zipper has been established for the first time by using an alpha/AApeptide zipper
      that assembles into a de novo lattice arrangement through two layers of hydrogen
      bonded linker-directed interactions. Via a covalently bridged 1D 413-helix,
      drastic enhancement in stability has been achieved in the formed 3D crystalline
      supramolecular architecture as evidenced by gas-sorption studies. As the first
      example of an unnatural peptidic zipper, the dimensional augmentation of the
      zipper differs from metal-coordinated strategies, and may have general
      implications for the preparation of peptidic functional materials for a variety
      of future applications.

PMID- 29590527
TI  - Dual-Readout Immunochromatographic Assay by Utilizing MnO2 Nanoflowers as the
      Unique Colorimetric/Chemiluminescent Probe.
AB  - Manganese dioxide nanoflowers (MnO2 NFs) were synthesized and used as a dual
      readout probe to develop a novel immunochromatographic test strip (ITS) for
      detecting pesticide residues using chlorpyrifos as the model analyte. MnO2 NFs
      labeled antibody for chlorpyrifos was employed as the signal tracer for
      conducting the ITS. After 10 min competitive immunoreaction, the tracer antibody
      was captured by the immobilized immunogen in the test strip, resulting in the
      captured MnO2 NFs on test line. The captured MnO2 NFs led to the appearance of
      brown color on the test line, which could be easily observed by the naked eye as
      a qualitative readout. Due to the very slight colorimetric difference of
      chlorpyrifos at trace concentrations, the semiquantitative readout by naked eyes
      could not meet the demand of quantitative analysis. MnO2 NFs showed a significant
      effect on the luminol-H2O2 chemiluminescent (CL) system, and the CL signal driven
      by MnO2 NFs were used to detect the trace concentration of chlorpyrifos
      quantitatively. 1,3-Diphenylisobenzofuran quenching studies and TMB-H2O2
      coloration assays were conducted for studying the enhancing mechanism of MnO2
      NFs, which was based on the oxidant activity to decompose H2O2 for forming
      reactive oxygen species. Under optimal conditions, the linear range of
      chlorpyrifos was 0.1-50 ng/mL with a low detection limit of 0.033 ng/mL (S/N =
      3). The reliability of the dual-readout ITS was successfully demonstrated by the
      application on traditional Chinese medicine and environmental water samples. Due
      to the simultaneous rapid-qualitative and sensitive-quantitative detection, the
      dual-readout protocol provides a promising strategy for rapid screening and field
      assay on various areas such as environmental monitoring and food safety.

PMID- 29590528
TI  - Interaction of the H-Cluster of FeFe Hydrogenase with Halides.
AB  - FeFe hydrogenases catalyze H2 oxidation and production using an "H-cluster",
      where two Fe ions are bound by an aza-dithiolate (adt) ligand. Various hypotheses
      have been proposed (by us and others) to explain that the enzyme reversibly
      inactivates under oxidizing, anaerobic conditions: intramolecular binding of the
      N atom of adt, formation of the so-called "Hox/inact" state or nonproductive
      binding of H2 to isomers of the H-cluster. Here, we show that none of the above
      explains the new finding that the anaerobic, oxidative, H2-dependent reversible
      inactivation is strictly dependent on the presence of Cl- or Br-. We provide
      experimental evidence that chloride uncompetitively inhibits the enzyme: it
      reversibly binds to catalytic intermediates of H2 oxidation (but not to the
      resting "Hox" state), after which oxidation locks the active site into a stable,
      saturated, inactive form, the structure of which is proposed here based on DFT
      calculations. The halides interact with the amine group of the H-cluster but do
      not directly bind to iron. It should be possible to stabilize the inhibited state
      in amounts compatible with spectroscopic investigations to explore further this
      unexpected reactivity of the H-cluster of hydrogenase.

PMID- 29590529
TI  - Measurement of Tau Filament Fragmentation Provides Insights into Prion-like
      Spreading.
AB  - The ordered assembly of amyloidogenic proteins causes a wide spectrum of common
      neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. These
      diseases share common features with prion diseases, in which misfolded proteins
      can self-replicate and transmit disease across different hosts. Deciphering the
      molecular mechanisms that underlie the amplification of aggregates is fundamental
      for understanding how pathological deposits can spread through the brain and
      drive disease. Here, we used single-molecule microscopy to study the assembly and
      replication of tau at the single aggregate level. We found that tau aggregates
      have an intrinsic ability to amplify by filament fragmentation, and determined
      the doubling times for this replication process by kinetic modeling. We then
      simulated the spreading time for aggregates through the brain and found this to
      be in good agreement with both the observed time frame for spreading of
      pathological tau deposits in Alzheimer's disease and in experimental models of
      tauopathies. With this work we begin to understand the physical parameters that
      govern the spreading rates of tau and other amyloids through the human brain.

PMID- 29590531
TI  - The Impact of Therapeutic Hypothermia on Pulmonary Hemodynamics of Meconium
      Aspiration Syndrome.

PMID- 29590530
TI  - Diatomic Metasurface for Vectorial Holography.
AB  - The emerging metasurfaces with the exceptional capability of manipulating an
      arbitrary wavefront have revived the holography with unprecedented prospects.
      However, most of the reported metaholograms suffer from limited polarization
      controls for a restrained bandwidth in addition to their complicated meta-atom
      designs with spatially variant dimensions. Here, we demonstrate a new concept of
      vectorial holography based on diatomic metasurfaces consisting of metamolecules
      formed by two orthogonal meta-atoms. On the basis of a simply linear relationship
      between phase and polarization modulations with displacements and orientations of
      identical meta-atoms, active diffraction of multiple polarization states and
      reconstruction of holographic images are simultaneously achieved, which is robust
      against both incident angles and wavelengths. Leveraging this appealing feature,
      broadband vectorial holographic images with spatially varying polarization states
      and dual-way polarization switching functionalities have been demonstrated,
      suggesting a new route to achromatic diffractive elements, polarization optics,
      and ultrasecure anticounterfeiting.

PMID- 29590532
TI  - Reply to Giesinger and McNamara: The Impact of Therapeutic Hypothermia on
      Pulmonary Hemodynamics of Meconium Aspiration Syndrome.

PMID- 29590533
TI  - Three Unresolved Issues in Human Morality.
AB  - This article discusses three major, but related, controversies surrounding the
      idea of morality. Is the complete pattern of features defining human morality
      unique to this species? How context dependent are moral beliefs and the emotions
      that often follow a violation of a moral standard? What developmental sequence
      establishes a moral code? This essay suggests that human morality rests on a
      combination of cognitive and emotional processes that are missing from the
      repertoires of other species. Second, the moral evaluation of every behavior,
      whether by self or others, depends on the agent, the action, the target of the
      behavior, and the context. The ontogeny of morality, which begins with processes
      that apes possess but adds language, inference, shame, and guilt, implies that
      humans are capable of experiencing blends of thoughts and feelings for which no
      semantic term exists. As a result, conclusions about a person's moral emotions
      based only on questionnaires or interviews are limited to this evidence.

PMID- 29590534
TI  - The role of IL-6 in exercise-induced anorexia in normal-weight boys.
AB  - Our previous study showed that interleukin-6 (IL-6) is associated with
      suppression of appetite after high-intensity exercise (HIEX), but an independent
      role in food intake (FI) was not defined. We hypothesized that IL-6 suppresses
      appetite and FI, independently of appetite hormones, after HIEX in normal-weight
      (NW) boys. We investigated the effect of HIEX, with and without the inflammation
      inhibitor ibuprofen (IBU), on IL-6, other biomarkers of inflammation and
      appetite, FI, and ratings of appetite in NW boys. Fifteen NW boys (aged 13-18
      years) were randomly assigned in a crossover design to 4 sessions: (i) water and
      rest, (ii) IBU and rest, (iii) water and HIEX, and (iv) IBU and HIEX. HIEX
      consisted of three 10-min bouts of exercise at 75% of maximal oxygen uptake with
      90 s of active rest between bouts. IBU (300 mg) was given as a liquid suspension.
      FI, ratings of appetite, and plasma biomarkers of appetite, inflammation, stress,
      and glucose control were measured. FI was not affected by HIEX or IBU. Appetite
      increased over time (p = 0.002) but was lower after HIEX (p < 0.001) and not
      affected by IBU. HIEX, but not IBU, resulted in higher levels of IL-6 (p < 0.001)
      and cortisol (p < 0.001) and lower active ghrelin (p < 0.001). IL-6 correlated
      with active ghrelin (r = 0.37; p = 0.036) and cortisol (r = 0.26; p = 0.049). An
      independent role for IL-6 in appetite suppression was not supported. However, IL
      6 was correlated with active ghrelin and cortisol, thus potentially mediating
      appetite via these interactions.

PMID- 29590535
TI  - Things We "kNOw" and Do Not "kNOw" about Pulmonary Hypertension.

PMID- 29590536
TI  - Alteration of DACH1 methylation patterns in lung cancer contributes to cell
      proliferation and migration.
AB  - Lung cancer is the most common cause of cancer-related death. Non-small cell lung
      cancer (NSCLC) accounts for 80%-85% of total lung cancer cases. Dachshund homolog
      1 (DACH1), is a protein encoded by the DACH1 gene in humans. DACH1 inhibits lung
      adenocarcinoma invasion and tumor growth but has a lower expression in NSCLC. To
      investigate the mechanisms of decreased DACH1 expression, its DNA methylation
      patterns were investigated. The results showed a higher methylation rate in NSCLC
      compared with the adjacent normal lung tissues. Cell transfection experiments
      showed that increased methylation impaired transcription factor transactivation.
      In vivo demethylation treatment and overexpression of DACH1 increased apoptosis
      and decreased migration and invasion in NSCLC A549 cells. Our research provides
      new insight into NSCLC pathogenesis and identifies a new therapeutic target.

PMID- 29590537
TI  - Assessing the mechanistic target of rapamycin complex-1 pathway in response to
      resistance exercise and feeding in human skeletal muscle by multiplex assay.
AB  - The mechanistic target of rapamycin complex-1 (mTORC-1) is a key nutrient and
      contraction-sensitive protein that regulates a pathway leading to skeletal muscle
      growth. Utilizing a multiplex assay, we aimed to examine the phosphorylation
      status of key mTORC-1-related signalling molecules in response to protein feeding
      and resistance exercise. Eight healthy men (age, 22.5 +/- 3.1 years; mass, 80 +/-
      9 kg; 1-repetition maximum leg extension, 87 +/- 5 kg) performed 4 sets of
      unilateral leg extensions until volitional failure. Immediately following the
      final set, all participants consumed a protein-enriched beverage. A single
      skeletal muscle biopsy was obtained from the vastus lateralis before (Pre) with
      further bilateral biopsies at 1 h (1 h exercised legs (FEDEX) and 1 h
      nonexercised legs (FED)) and 3 h (3 h FEDEX and 3 h FED) after drink ingestion.
      Phosphorylated AktSer473 was significantly elevated from Pre at 1 h FEDEX.
      Phosphorylated p70S6K1Thr412 was significantly increased above Pre at 1 h FEDEX
      and 1 h FED and was still significantly elevated at 3 h FEDEX but not 3 h FED.
      Phosphorylated rpS6Ser235/236 was also significantly increased above Pre at 1 h
      FEDEX and 1 h FED with 1 h FEDEX greater than 1 h FED. Our data highlight the
      utility of a multiplex assay to assess anabolic signalling molecules in response
      to protein feeding and resistance exercise in humans. Importantly, these changes
      are comparable with those as previously reported using standard immunoblotting
      and protein activity assays.

PMID- 29590538
TI  - STAT3 Gain of Function: A New Kid on the Block in Interstitial Lung Diseases.

PMID- 29590539
TI  - A New IDEA in Adjuvant Chemotherapy for Colon Cancer.

PMID- 29590540
TI  - Osimertinib in EGFR Mutation-Positive Advanced NSCLC.

PMID- 29590541
TI  - Are We Prepared for Nuclear Terrorism?

PMID- 29590542
TI  - Rethinking Criminalization of HIV Exposure - Lessons from California's New
      Legislation.

PMID- 29590543
TI  - Case 10-2018: An 84-Year-Old Man with Painless Unilateral Testicular Swelling.

PMID- 29590545
TI  - Clonal Hematopoiesis after Induction Chemotherapy for Acute Myeloid Leukemia.

PMID- 29590546
TI  - Cutaneous Diphtheria.

PMID- 29590544
TI  - Duration of Adjuvant Chemotherapy for Stage III Colon Cancer.
AB  - BACKGROUND: Since 2004, a regimen of 6 months of treatment with oxaliplatin plus
      a fluoropyrimidine has been standard adjuvant therapy in patients with stage III
      colon cancer. However, since oxaliplatin is associated with cumulative
      neurotoxicity, a shorter duration of therapy could spare toxic effects and health
      expenditures. METHODS: We performed a prospective, preplanned, pooled analysis of
      six randomized, phase 3 trials that were conducted concurrently to evaluate the
      noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin,
      and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3
      months, as compared with 6 months. The primary end point was the rate of disease
      free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy
      could be claimed if the upper limit of the two-sided 95% confidence interval of
      the hazard ratio did not exceed 1.12. RESULTS: After 3263 events of disease
      recurrence or death had been reported in 12,834 patients, the noninferiority of 3
      months of treatment versus 6 months was not confirmed in the overall study
      population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15).
      Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95%
      CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26).
      In an exploratory analysis of the combined regimens, among the patients with T1,
      T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a
      3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard
      ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were
      classified as T4, N2, or both, the disease-free survival rate for a 6-month
      duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%)
      for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for
      superiority). CONCLUSIONS: Among patients with stage III colon cancer receiving
      adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as
      compared with 6 months, was not confirmed in the overall population. However, in
      patients treated with CAPOX, 3 months of therapy was as effective as 6 months,
      particularly in the lower-risk subgroup. (Funded by the National Cancer Institute
      and others.).

PMID- 29590548
TI  - The Verge of Collapse.

PMID- 29590547
TI  - Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma.
AB  - BACKGROUND: Both the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax
      are active as monotherapy in the treatment of mantle-cell lymphoma. Complete
      response rates of 21% have been observed for each agent when administered as long
      term continuous therapy. Preclinical models predict synergy in combination.
      METHODS: We conducted a single-group, phase 2 study of daily oral ibrutinib and
      venetoclax in patients, as compared with historical controls. Patients commenced
      ibrutinib monotherapy at a dose of 560 mg per day. After 4 weeks, venetoclax was
      added in stepwise, weekly increasing doses to 400 mg per day. Both drugs were
      continued until progression or an unacceptable level of adverse events. The
      primary end point was the rate of complete response at week 16. Minimal residual
      disease (MRD) was assessed by flow cytometry in bone marrow and by allele
      specific oligonucleotide-polymerase chain reaction (ASO-PCR) in blood. RESULTS:
      The study included 24 patients with relapsed or refractory mantle-cell lymphoma
      (23 patients) or previously untreated mantle-cell lymphoma (1 patient). Patients
      were 47 to 81 years of age, and the number of previous treatments ranged from
      none to six. Half the patients had aberrations of TP53, and 75% had a high-risk
      prognostic score. The complete response rate according to computed tomography at
      week 16 was 42%, which was higher than the historical result of 9% at this time
      point with ibrutinib monotherapy (P<0.001). The rate of complete response as
      assessed by positron-emission tomography was 62% at week 16 and 71% overall. MRD
      clearance was confirmed by flow cytometry in 67% of the patients and by ASO-PCR
      in 38%. In a time-to-event analysis, 78% of the patients with a response were
      estimated to have an ongoing response at 15 months. The tumor lysis syndrome
      occurred in 2 patients. Common side effects were generally low grade and included
      diarrhea (in 83% of the patients), fatigue (in 75%), and nausea or vomiting (in
      71%). CONCLUSIONS: In this study involving historical controls, dual targeting of
      BTK and BCL2 with ibrutinib and venetoclax was consistent with improved outcomes
      in patients with mantle-cell lymphoma who had been predicted to have poor
      outcomes with current therapy. (Funded by Janssen and others; AIM
      ClinicalTrials.gov number, NCT02471391 .).

PMID- 29590549
TI  - Influenza Vaccination during Pregnancy and Protection against Pertussis.

PMID- 29590550
TI  - Polluting Developing Brains - EPA Failure on Chlorpyrifos.

PMID- 29590551
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29590552
TI  - Various transgenic mouse lines to study proopiomelanocortin cells in the brain
      stem label disparate populations of GABAergic and glutamatergic neurons.
AB  - Products of the proopiomelanocortin (POMC) prohormone regulate aspects of
      analgesia, reward, and energy balance; thus, the neurons that produce POMC in the
      hypothalamus have received considerable attention. However, there are also cells
      in the nucleus of the solitary tract (NTS) that transcribe Pomc, although low
      levels of Pomc mRNA and relative lack of POMC peptide products in the adult mouse
      NTS have hindered the study of these cells. Therefore, studies of NTS POMC cells
      have largely relied on transgenic mouse lines. Here, we set out to determine the
      amino acid (AA) transmitter phenotype of NTS POMC neurons by using Pomc-Gfp
      transgenic mice to identify POMC cells. We found that cells expressing the green
      fluorescent protein (GFP) represent a mix of GABAergic and glutamatergic cells as
      indicated by Gad2 and vesicular Glut2 ( vGlut2) mRNA expression, respectively. We
      then examined the AA phenotype of POMC cells labeled by a Pomc-Cre transgene and
      found that these are also a mix of GABAergic and glutamatergic cells. However,
      the NTS cells labeled by the Gfp- and Cre-containing transgenes represented
      distinct populations of cells in three different Pomc-Cre mouse lines. Consistent
      with previous work, we were unable to reliably detect Pomc mRNA in the NTS
      despite clear expression in the hypothalamus. Thus, it was not possible to
      determine which transgenic tool most accurately identifies NTS cells that may
      express Pomc or release POMC peptides, although the results indicate the
      transgenic tools for study of these NTS neurons can label disparate populations
      of cells with varied AA phenotypes.

PMID- 29590554
TI  - Lateral septum growth hormone secretagogue receptor affects food intake and
      motivation for sucrose reinforcement.
AB  - The hormone ghrelin promotes eating and is widely considered to be a hunger
      signal. Ghrelin receptors, growth hormone secretagogue receptors (GHSRs), are
      found in a number of specific regions throughout the brain, including the lateral
      septum (LS), an area not traditionally associated with the control of feeding.
      Here we investigated whether GHSRs in the LS play a role in the control of food
      intake. We examined the feeding effects of ghrelin and the GHSR antagonists ([d
      Lys3]-growth hormone-releasing peptide-6 and JMV-2959) at doses subthreshold for
      effect when delivered to the lateral ventricle. Intra-LS ghrelin significantly
      increased chow intake during the midlight phase, suggesting that pharmacological
      activation of LS GHSRs promotes feeding. Conversely, GHSR antagonist delivered to
      the LS shortly before dark onset significantly reduced chow intake. These data
      support the hypothesis that exogenous and endogenous stimulation of GHSRs in the
      LS influence feeding. Ghrelin is known to affect motivation for food, and the
      dorsal subdivision of LS (dLS) has been shown to play a role in motivation. Thus,
      we investigated the role of dLS GHSRs in motivation for food reward by examining
      operant responding for sucrose on a progressive ratio (PR) schedule. Intra-dLS
      ghrelin increased PR responding for sucrose, whereas blockade of LS GHSRs did not
      affect responding in either a fed or fasted state. Together these findings for
      the first time substantiate the LS as a site of action for ghrelin signaling in
      the control of food intake.

PMID- 29590555
TI  - Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue
      thermogenesis, arterial pressure, and heart rate.
AB  - The sympathetic nerve activity (SNA) to brown adipose tissue (BAT) regulates BAT
      thermogenesis to defend body temperature in cold environments or to produce fever
      during immune responses. The vagus nerve contains afferents that inhibit the BAT
      SNA and BAT thermogenesis evoked by skin cooling. We sought to determine whether
      activation of transient receptor potential vanilloid 1 (TRPV1) channels in the
      nucleus tractus solitarius (NTS), which are prominently expressed in unmyelinated
      vagal afferents, would affect cold-evoked BAT thermogenesis, cardiovascular
      parameters, or their vagal afferent-evoked responses. In urethane-chloralose
      anesthetized rats, during skin cooling, nanoinjection of the TRPV1-agonist
      resiniferatoxin in NTS decreased BAT SNA (from 695 +/- 195% of baseline during
      cooling to 103 +/- 8% of baseline after resiniferatoxin), BAT temperature (-0.8
      +/- 0.1 degrees C), expired CO2 (-0.3 +/- 0.04%), mean arterial pressure (MAP; 
      20 +/- 5 mmHg), and heart rate (-44 +/- 11 beats/min). Pretreatment of NTS with
      the TRPV1 antagonist capsazepine prevented these resiniferatoxin-mediated
      effects. Intravenous injection of the TRPV1 agonist dihydrocapsaicin also
      decreased all the measured variables (except MAP). Bilateral cervical or
      subdiaphragmatic vagotomy attenuated the decreases in BAT SNA and thermogenesis
      evoked by nanoinjection of resiniferatoxin in NTS but did not prevent the
      decreases in BAT SNA and BAT thermogenesis evoked by intravenous
      dihydrocapsaicin. We conclude that activation of TRPV1 channels in the NTS of
      vagus nerve intact rats inhibits BAT SNA and decreases BAT metabolism, blood
      pressure, and heart rate. In contrast, the inhibition of BAT thermogenesis
      following systemic administration of dihydrocapsaicin does not require vagal
      afferent activity, consistent with a nonvagal pathway through which systemic
      TRPV1 agonists can inhibit BAT thermogenesis.

PMID- 29590553
TI  - Targeting pain at its source in sickle cell disease.
AB  - Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia,
      end-organ damage, reduced survival, and pain. One of the unique features of SCD
      is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis
      requiring hospitalization. Additionally, patients with SCD often develop chronic
      persistent pain. Currently, sickle cell pain is treated with opioids, an approach
      limited by adverse effects. Because pain can start at infancy and continue
      throughout life, preventing the genesis of pain may be relatively better than
      treating the pain once it has been evoked. Therefore, we provide insights into
      the cellular and molecular mechanisms of sickle cell pain that contribute to the
      activation of the somatosensory system in the peripheral and central nervous
      systems. These mechanisms include mast cell activation and neurogenic
      inflammation, peripheral nociceptor sensitization, maladaptation of spinal
      signals, central sensitization, and modulation of neural circuits in the brain.
      In this review, we describe potential preventive/therapeutic targets and their
      targeting with novel pharmacologic and/or integrative approaches to ameliorate
      sickle cell pain.

PMID- 29590556
TI  - Mitochondrial basis for sex-differences in metabolism and exercise performance.

PMID- 29590557
TI  - Response of catecholaminergic neurons in the mouse hindbrain to glucoprivic
      stimuli is astrocyte dependent.
AB  - Hindbrain catecholaminergic (CA) neurons are required for critical autonomic,
      endocrine, and behavioral counterregulatory responses (CRRs) to hypoglycemia.
      Recent studies suggest that CRR initiation depends on hindbrain astrocyte glucose
      sensors (McDougal DH, Hermann GE, Rogers RC. Front Neurosci 7: 249, 2013; Rogers
      RC, Ritter S, Hermann GE. Am J Physiol Regul Integr Comp Physiol 310: R1102
      R1108, 2016). To test the proposition that hindbrain CA responses to
      glucoprivation are astrocyte dependent, we utilized transgenic mice in which the
      calcium reporter construct (GCaMP5) was expressed selectively in tyrosine
      hydroxylase neurons (TH-GCaMP5). We conducted live cell calcium-imaging studies
      on tissue slices containing the nucleus of the solitary tract (NST) or the
      ventrolateral medulla, critical CRR initiation sites. Results show that TH-GCaMP5
      neurons are robustly activated by a glucoprivic challenge and that this response
      is dependent on functional astrocytes. Pretreatment of hindbrain slices with
      fluorocitrate (an astrocytic metabolic suppressor) abolished TH-GCaMP5 neuronal
      responses to glucoprivation, but not to glutamate. Pharmacologic results suggest
      that the astrocytic connection with hindbrain CA neurons is purinergic via P2
      receptors. Parallel imaging studies on hindbrain slices of NST from wild-type
      C57BL/6J mice, in which astrocytes and neurons were prelabeled with a calcium
      reporter dye and an astrocytic vital dye, show that both cell types are activated
      by glucoprivation but astrocytes responded significantly sooner than neurons.
      Pretreatment of these hindbrain slices with P2 antagonists abolished neuronal
      responses to glucoprivation without interruption of astrocyte responses;
      pretreatment with fluorocitrate eliminated both astrocytic and neuronal
      responses. These results support earlier work suggesting that the primary
      detection of glucoprivic signals by the hindbrain is mediated by astrocytes.

PMID- 29590559
TI  - Decreased prefrontal oxygenation elicited by stimulation of limb mechanosensitive
      afferents during cycling exercise.
AB  - Our laboratory reported using near-infrared spectroscopy that feedback from limb
      mechanoafferents may decrease prefrontal oxygenated-hemoglobin concentration (Oxy
      Hb) during the late period of voluntary and passive cycling. To test the
      hypothesis that the decreased Oxy-Hb of the prefrontal cortex would be augmented
      depending on the extent of limb mechanoafferent input, the prefrontal Oxy-Hb
      response was measured during motor-driven one- and two-legged passive cycling for
      1 min at various revolutions of pedal movement in 19 subjects. Furthermore, we
      examined whether calculated tissue oxygenation index (TOI) decreased during
      passive cycling as the Oxy-Hb did, simultaneously assessing blood flows of
      extracranial cutaneous tissue and the common and internal carotid arteries (CCA
      and ICA) with laser and ultrasound Doppler flowmetry. Minute ventilation and
      cardiac output increased and peripheral resistance decreased during passive
      cycling, depending on both revolutions of pedal movement and number of limbs,
      whereas mean arterial blood pressure did not change. Passive cycling did not
      change end-tidal CO2, suggesting absence of a hypocapnic change. Prefrontal Oxy
      Hb decreased during passive cycling, being in proportion to revolution of pedal
      movement but not number of cycling limbs. In addition, prefrontal TOI decreased
      during passive cycling as Oxy-Hb did, whereas blood flows of forehead cutaneous
      tissue, CCA, and ICA did not change significantly. Thus, a decrease in Oxy-Hb
      reflected a decrease in tissue blood flow of the intracerebral vasculature but
      not the extracerebral compartment. It is likely that feedback from
      mechanoafferents decreased regional cerebral blood flow of the prefrontal cortex
      in relation to the revolutions of pedal movement.

PMID- 29590558
TI  - Insulin increases ventilation during euglycemia in humans.
AB  - Evidence from animal studies indicates that hyperinsulinemia, without changes in
      glucose, increases ventilation via a carotid body-mediated mechanism. However,
      whether insulin elevates ventilation in humans independently of changes in
      glucose remains unclear. Therefore, we tested the hypothesis that insulin
      increases ventilation in humans during a hyperinsulinemic-euglycemic clamp in
      which insulin was elevated to postprandial concentrations while glucose was
      maintained at fasting concentrations. First, in 16 healthy young men ( protocol
      1), we retrospectively analyzed respiration rate and estimated tidal volume from
      a pneumobelt to calculate minute ventilation during a hyperinsulinemic-euglycemic
      clamp. In addition, for a direct assessment of minute ventilation during a
      hyperinsulinemic-euglycemic clamp, we retrospectively analyzed breath-by-breath
      respiration rate and tidal volume from inspired/expired gasses in an additional
      23 healthy young subjects ( protocol 2). Clamp infusion elevated minute
      ventilation from baseline in both protocols ( protocol 1: +11.9 +/- 4.6%
      baseline, P = 0.001; protocol 2: +9.5 +/- 3.8% baseline, P = 0.020). In protocol
      1, peak changes in both respiration rate (+13.9 +/- 3.0% baseline, P < 0.001) and
      estimated tidal volume (+16.9 +/- 4.1% baseline, P = 0.001) were higher than
      baseline during the clamp. In protocol 2, tidal volume primarily increased during
      the clamp (+9.7 +/- 3.7% baseline, P = 0.016), as respiration rate did not change
      significantly (+0.2 +/- 1.8% baseline, P = 0.889). Collectively, we demonstrate
      for the first time in humans that elevated plasma insulin increases minute
      ventilation independent of changes in glucose.

PMID- 29590581
TI  - Bigger Isn't Always Better: Bulking Up Impedes Receptor Internalization.

PMID- 29590582
TI  - Topotaxis: A New Mechanism of Directed Cell Migration in Topographic ECM
      Gradients.
AB  - Living cells orient the cytoskeleton polarity and directional migration in
      response to spatial gradients of multiple types of cues. The resulting tactic
      behaviors are critical for the proper cell localization in the context of complex
      single-cell and tissue behaviors. In this perspective, we highlight the recent
      discovery of, to our knowledge, a new -taxis phenomenon, the topotaxis, which
      mediates directional cell migration in response to the gradients of such
      topographic features as the density of extracellular matrix fibers. The direction
      of topotactic migration critically depends on the effective stiffness of the
      cortical cytoskeleton, which is controlled by the balance between two parallel
      signaling pathways activated by the extracellular matrix input. Topotaxis can
      account for such striking cell behaviors as the opposite directionality of
      migration of benign and metastatic cancer cells and certain aspects of the wound
      healing process. We anticipate that, in conjunction with other tactic phenomena,
      topotaxis can provide critical information for understanding and design of tissue
      structure and function.

PMID- 29590583
TI  - Fodis: Software for Protein Unfolding Analysis.
AB  - The folding dynamics of proteins at the single-molecule level has been studied
      with single-molecule force spectroscopy experiments for 20 years, but a common
      standardized method for the analysis of the collected data and for sharing among
      the scientific community members is still not available. We have developed a new
      open-source tool-Fodis-for the analysis of the force-distance curves obtained in
      single-molecule force spectroscopy experiments, providing almost automatic
      processing, analysis, and classification of the obtained data. Our method
      provides also a classification of the possible unfolding pathways and the
      structural heterogeneity present during the unfolding of proteins.

PMID- 29590584
TI  - CONAN: A Tool to Decode Dynamical Information from Molecular Interaction Maps.
AB  - The analysis of contacts is a powerful tool to understand biomolecular function
      in a series of contexts, from the investigation of dynamical behavior at
      equilibrium to the study of nonequilibrium dynamics in which the system moves
      between multiple states. We thus propose a tool called CONtact ANalysis (CONAN)
      that, from molecular dynamics (MD) trajectories, analyzes interresidue contacts,
      creates videos of time-resolved contact maps, and performs correlation, principal
      component, and cluster analysis, revealing how specific contacts relate to
      functionally relevant states sampled by MD. We present how CONAN can identify
      features describing the dynamics of ubiquitin both at equilibrium and during
      mechanical unfolding. Additionally, we show the analysis of MD trajectories of an
      alpha-synuclein mutant peptide that undergoes an alpha-beta conformational
      transition that can be easily monitored using CONAN, which identifies the
      multiple states that the peptide explores along its conformational dynamics. The
      high versatility and ease of use of the software make CONAN a tool that can
      significantly facilitate the understanding of the complex dynamical behavior of
      proteins or other biomolecules. CONAN and its documentation are freely available
      for download on GitHub.

PMID- 29590586
TI  - Human Blue Cone Opsin Regeneration Involves Secondary Retinal Binding with Analog
      Specificity.
AB  - Human color vision is mediated by the red, green, and blue cone visual pigments.
      Cone opsins are G-protein-coupled receptors consisting of an opsin apoprotein
      covalently linked to the 11-cis-retinal chromophore. All visual pigments share a
      common evolutionary origin, and red and green cone opsins exhibit a higher
      homology, whereas blue cone opsin shows more resemblance to the dim light
      receptor rhodopsin. Here we show that chromophore regeneration in photoactivated
      blue cone opsin exhibits intermediate transient conformations and a secondary
      retinoid binding event with slower binding kinetics. We also detected a fine
      tuning of the conformational change in the photoactivated blue cone opsin binding
      site that alters the retinal isomer binding specificity. Furthermore, the
      molecular models of active and inactive blue cone opsins show specific molecular
      interactions in the retinal binding site that are not present in other opsins.
      These findings highlight the differential conformational versatility of human
      cone opsin pigments in the chromophore regeneration process, particularly
      compared to rhodopsin, and point to relevant functional, unexpected roles other
      than spectral tuning for the cone visual pigments.

PMID- 29590585
TI  - Hexahydrated Mg2+ Binding and Outer-Shell Dehydration on RNA Surface.
AB  - The interaction between metal ions, especially Mg2+ ions, and RNA plays a
      critical role in RNA folding. Upon binding to RNA, a metal ion that is fully
      hydrated in bulk solvent can become dehydrated. Here we use molecular dynamics
      simulation to investigate the dehydration of bound hexahydrated Mg2+ ions. We
      find that a hydrated Mg2+ ion in the RNA groove region can involve significant
      dehydration in the outer hydration shell. The first or innermost hydration shell
      of the Mg2+ ion, however, is retained during the simulation because of the strong
      ion-water electrostatic attraction. As a result, water-mediated hydrogen bonding
      remains an important form for Mg2+-RNA interaction. Analysis for ions at
      different binding sites shows that the most pronounced water deficiency relative
      to the fully hydrated state occurs at a radial distance of around 11 A from the
      center of the ion. Based on the independent 200 ns molecular dynamics simulations
      for three different RNA structures (Protein Data Bank: 1TRA, 2TPK, and 437D), we
      find that Mg2+ ions overwhelmingly dominate over monovalent ions such as Na+ and
      K+ in ion-RNA binding. Furthermore, application of the free energy perturbation
      method leads to a quantitative relationship between the Mg2+ dehydration free
      energy and the local structural environment. We find that DeltaDeltaGhyd, the
      change of the Mg2+ hydration free energy upon binding to RNA, varies linearly
      with the inverse distance between the Mg2+ ion and the nearby nonbridging oxygen
      atoms of the phosphate groups, and DeltaDeltaGhyd can reach -2.0 kcal/mol and 
      3.0 kcal/mol for an Mg2+ ion bound to the surface and to the groove interior,
      respectively. In addition, the computation results in an analytical formula for
      the hydration ratio as a function of the average inverse Mg2+-O distance. The
      results here might be useful for further quantitative investigations of ion-RNA
      interactions in RNA folding.

PMID- 29590587
TI  - Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome
      Release.
AB  - Genome ejection proteins are required to facilitate transport of bacteriophage
      P22 double-stranded DNA safely through membranes of Salmonella. The structures
      and locations of all proteins in the context of the mature virion are known, with
      the exception of three ejection proteins. Furthermore, the changes that occur to
      the proteins residing in the mature virion upon DNA release are not fully
      understood. We used cryogenic electron microscopy to obtain what is, to our
      knowledge, the first asymmetric reconstruction of mature bacteriophage P22 after
      double-stranded DNA has been extruded from the capsid-a state representative of
      one step during viral infection. Results of icosahedral and asymmetric
      reconstructions at estimated resolutions of 7.8 and 12.5 A resolutions,
      respectively, are presented. The reconstruction shows tube-like protein density
      extending from the center of the tail assembly. The portal protein does not
      revert to the more contracted, procapsid state, but instead maintains an extended
      and splayed barrel structure. These structural details contribute to our
      understanding of the molecular mechanism of P22 phage infection and also set the
      foundation for future exploitation serving engineering purposes.

PMID- 29590589
TI  - Molecular Mechanisms of Tight Binding through Fuzzy Interactions.
AB  - Many intrinsically disordered proteins (IDPs) form fuzzy complexes upon binding
      to their targets. Although many IDPs are weakly bound in fuzzy complexes, some
      IDPs form high-affinity complexes. One example is the nonstructural protein 1
      (NS1) of the 1918 Spanish influenza A virus, which hijacks cellular CRKII through
      the strong binding affinity (Kd ~10 nM) of its proline-rich motif (PRMNS1) to the
      N-terminal Src-homology 3 domain of CRKII. However, its molecular mechanism
      remains elusive. Here, we examine the interplay between structural disorder of a
      bound PRMNS1 and its long-range electrostatic interactions. Using x-ray
      crystallography and NMR spectroscopy, we found that PRMNS1 retains substantial
      conformational flexibility in the bound state. Moreover, molecular dynamics
      simulations showed that structural disorder of the bound PRMNS1 increases the
      number of electrostatic interactions and decreases the mean distances between the
      positively charged residues in PRMNS1 and the acidic residues in the N-terminal
      Src-homology 3 domain. These results are analyzed using a polyelectrostatic
      model. Our results provide an insight into the molecular recognition mechanism
      for a high-affinity fuzzy complex.

PMID- 29590588
TI  - Active Site Flexibility as a Hallmark for Efficient PET Degradation by I.
      sakaiensis PETase.
AB  - Polyethylene terephthalate (PET) is one of the most-consumed synthetic polymers,
      with an annual production of 50 million tons. Unfortunately, PET accumulates as
      waste and is highly resistant to biodegradation. Recently, fungal and bacterial
      thermophilic hydrolases were found to catalyze PET hydrolysis with optimal
      activities at high temperatures. Strikingly, an enzyme from Ideonella sakaiensis,
      termed PETase, was described to efficiently degrade PET at room temperature, but
      the molecular basis of its activity is not currently understood. Here, a crystal
      structure of PETase was determined at 2.02 A resolution and employed in molecular
      dynamics simulations showing that the active site of PETase has higher
      flexibility at room temperature than its thermophilic counterparts. This
      flexibility is controlled by a novel disulfide bond in its active site, with its
      removal leading to destabilization of the catalytic triad and reduction of the
      hydrolase activity. Molecular docking of a model substrate predicts that PET
      binds to PETase in a unique and energetically favorable conformation facilitated
      by several residue substitutions within its active site when compared to other
      enzymes. These computational predictions are in excellent agreement with recent
      mutagenesis and PET film degradation analyses. Finally, we rationalize the
      increased catalytic activity of PETase at room temperature through molecular
      dynamics simulations of enzyme-ligand complexes for PETase and other thermophilic
      PET-degrading enzymes at 298, 323, and 353 K. Our results reveal that both the
      binding pose and residue substitutions within PETase favor proximity between the
      catalytic residues and the labile carbonyl of the substrate at room temperature,
      suggesting a more favorable hydrolytic reaction. These results are valuable for
      enabling detailed evolutionary analysis of PET-degrading enzymes and for rational
      design endeavors aiming at increasing the efficiency of PETase and similar
      enzymes toward plastic degradation.

PMID- 29590590
TI  - Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane
      Alterations.
AB  - The bile acid-sensitive ion channel is activated by amphiphilic substances such
      as bile acids or artificial detergents via membrane alterations; however, the
      mechanism of membrane sensitivity of the bile acid-sensitive ion channel is not
      known. It has also not been systematically investigated whether other members of
      the degenerin/epithelial Na+ channel (DEG/ENaC) gene family are affected by
      amphiphilic compounds. Here, we show that DEG/ENaCs ASIC1a, ASIC3, ENaC, and the
      purinergic receptor P2X2 are modulated by a large number of different,
      structurally unrelated amphiphilic substances, namely the detergents N
      lauroylsarcosine, Triton X-100, and beta-octylglucoside; the fenamate flufenamic
      acid; the antipsychotic drug chlorpromazine; the natural phenol resveratrol; the
      chili pepper compound capsaicin; the loop diuretic furosemide; and the
      antiarrythmic agent verapamil. We determined the modification of membrane
      properties using large-angle x-ray diffraction experiments on model lipid
      bilayers, revealing that the amphiphilic compounds are positioned in a
      characteristic fashion either in the lipid tail group region or in the lipid head
      group region, demonstrating that they perturbed the membrane structure.
      Collectively, our results show that DEG/ENaCs and structurally related P2X
      receptors are modulated by diverse amphiphilic molecules. Furthermore, they
      suggest alterations of membrane properties by amphiphilic compounds as a
      mechanism contributing to modulation.

PMID- 29590591
TI  - Mechanism of Mechanosensitive Gating of the TREK-2 Potassium Channel.
AB  - The mechanism of mechanosensitive gating of ion channels underlies many
      physiological processes, including the sensations of touch, hearing, and pain
      perception. TREK-2 is the best-studied mechanosensitive member of the two-pore
      domain potassium channel family. Apart from pressure sensing, it responds to a
      diverse range of stimuli. Two states, termed "up" and "down," are known from x
      ray structural crystallographic studies and have been suggested to differ in
      conductance. However, the structural details of the gating behavior are largely
      unknown. In this work, we used molecular dynamics simulations to study the
      conductance of the states as well as the effect of mechanical membrane stretch on
      the channel. We find that the down state is less conductive than the up state.
      The introduction of membrane stretch in the simulations shifts the state of the
      channel toward an up configuration, independent of the starting configuration,
      and also increases its conductance. The correlation of the selectivity filter
      state and the conductance supports a model in which the selectivity filter gates
      by a carbonyl flip. This gate is stabilized by the pore helices. We suggest a
      modulation of these helices by an interface to the transmembrane helices.
      Membrane pressure changes the conformation of the transmembrane helices directly
      and consequently also influences the channel conductance.

PMID- 29590592
TI  - The Phase Behavior and Organization of Sphingomyelin/Cholesterol Membranes: A
      Deuterium NMR Study.
AB  - We have studied the dependence of the phase and domain characteristics of
      sphingomyelin (SM)/cholesterol model membranes on sterol content and temperature
      using deuterium nuclear magnetic resonance. NMR spectra of N-palmitoyl(D31)-D
      erythro-sphingosylphosphorylcholine (PSM-d31) were taken for temperatures from 25
      to 70 degrees C and cholesterol concentrations of 0-40%. Analogous experiments
      were performed using 1-palmitoyl,2-palmitoyl(D31)-sn-glycero-3-phosphocholine
      (DPPC-d31)/cholesterol membranes to carefully compare the data obtained using
      palmitoyl chains that have similar "kinked" conformations. The constructed phase
      diagrams exhibit both solid-ordered (so) + liquid-ordered (lo) and liquid
      disordered (ld) + lo phase-coexistence regions with a clear three-phase line.
      Macroscopic (micron-sized) coexistence of ld and lo phases was not observed;
      instead, line-broadening in the ld+lo region was characterized by intermediate
      exchange of lipids between the two types of domains. The length scales associated
      with the domains were estimated to be 75-150 nm for PSM-d31/cholesterol and DPPC
      d31/cholesterol model membranes.

PMID- 29590594
TI  - A New Method of Assessing Lipid Mixtures by 31P Magic-Angle Spinning NMR.
AB  - A variety of lipids that differ by their chains and headgroups are found in
      biomembranes. In addition to studying the overall membrane phase, determination
      of the structure, dynamics, and headgroup conformation of individual lipids in
      the mixture would be of great interest. We have thus developed, to our knowledge,
      a new approach using solid-state 31P NMR, magic-angle spinning, and chemical
      shift anisotropy (CSA) recoupling, using an altered version of the recoupling of
      chemical shift anisotropy (ROCSA) pulse sequence, here penned PROCSA. The
      resulting two-dimensional spectra allowed the simultaneous measurement of the
      isotropic chemical shift and CSA of each lipid headgroup, thus providing a
      valuable measure of its dynamics and structure. PROCSA was applied to mixtures of
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in various relative
      proportions, to mimic bacterial membranes and assess the respective roles of
      lipids in shaping these bilayers. The results were interpreted in terms of
      membrane topology, lipid propensity to adopt various phases or conformations, and
      lipid-lipid miscibility. Our results showed that PG dictates the lipid behavior
      when present in a proportion of 20 mol % or more. A small proportion of PG is
      thus able to impose a bilayer structure to the hexagonal phase forming PE. We
      discuss the requirement for lipids, such as PE, to be able to adopt non-bilayer
      phases in a membrane.

PMID- 29590593
TI  - Toxic HypF-N Oligomers Selectively Bind the Plasma Membrane to Impair Cell
      Adhesion Capability.
AB  - The deposition of fibrillar protein aggregates in human organs is the hallmark of
      several pathological states, including highly debilitating neurodegenerative
      disorders and systemic amyloidoses. It is widely accepted that small oligomers
      arising as intermediates in the aggregation process, released by fibrils, or
      growing in secondary nucleation steps are the cytotoxic entities in protein
      misfolding diseases, notably neurodegenerative conditions. Increasing evidence
      indicates that cytotoxicity is triggered by the interaction between nanosized
      protein aggregates and cell membranes, even though little information on the
      molecular details of such interaction is presently available. In this work, we
      propose what is, to our knowledge, a new approach, based on the use of single
      cell force spectroscopy applied to multifunctional substrates, to study the
      interaction between protein oligomers, cell membranes, and/or the extracellular
      matrix. We compared the interaction of single Chinese hamster ovary cells with
      two types of oligomers (toxic and nontoxic) grown from the N-terminal domain of
      the Escherichia coli protein HypF. We were able to quantify the affinity between
      both oligomer type and the cell membrane by measuring the mechanical work needed
      to detach the cells from the aggregates, and we could discriminate the
      contributions of the membrane lipid and protein fractions to such affinity. The
      fundamental role of the ganglioside GM1 in the membrane-oligomers interaction was
      also highlighted. Finally, we observed that the binding of toxic oligomers to the
      cell membrane significantly affects the functionality of adhesion molecules such
      as Arg-Gly-Asp binding integrins, and that this effect requires the presence of
      the negatively charged sialic acid moiety of GM1.

PMID- 29590595
TI  - Entropic Control of Receptor Recycling Using Engineered Ligands.
AB  - Receptor internalization by endocytosis regulates diverse cellular processes,
      from the rate of nutrient uptake to the timescale of essential signaling events.
      The established view is that internalization is tightly controlled by specific
      protein-binding interactions. However, recent work suggests that physical aspects
      of receptors influence the process in ways that cannot be explained by
      biochemistry alone. Specifically, work from several groups suggests that
      increasing the steric bulk of receptors may inhibit their uptake by multiple
      types of trafficking vesicles. How do biochemical and biophysical factors work
      together to control internalization? Here, we show that receptor uptake is well
      described by a thermodynamic trade-off between receptor-vesicle binding energy
      and the entropic cost of confining receptors within endocytic vesicles.
      Specifically, using large ligands to acutely increase the size of engineered
      variants of the transferrin receptor, we demonstrate that an increase in the
      steric bulk of a receptor dramatically decreases its probability of uptake by
      clathrin-coated structures. Further, in agreement with a simple thermodynamic
      analysis, all data collapse onto a single trend relating fractional occupancy of
      the endocytic structure to fractional occupancy of the surrounding plasma
      membrane, independent of receptor size. This fundamental scaling law provides a
      simple tool for predicting the impact of receptor expression level, steric bulk,
      and the size of endocytic structures on receptor uptake. More broadly, this work
      suggests that bulky ligands could be used to drive the accumulation of specific
      receptors at the plasma membrane surface, providing a biophysical tool for
      targeted modulation of signaling and metabolism from outside the cell.

PMID- 29590596
TI  - Atomistic Scale Effects of Lipopolysaccharide Modifications on Bacterial Outer
      Membrane Defenses.
AB  - Lipopolysaccharides (LPS) are a main constituent of the outer membrane of Gram
      negative bacteria. Salmonella enterica, like many other bacterial species, are
      able to chemically modify the structure of their LPS molecules through the PhoPQ
      pathway as a defense mechanism against the host immune response. These
      modifications make the outer membrane more resistant to antimicrobial peptides
      (AMPs), large lipophilic drugs, and cation depletion, and are crucial for
      survival within a host organism. It is believed that these LPS modifications
      prevent the penetration of large molecules and AMPs through a strengthening of
      lateral interactions between neighboring LPS molecules. Here, we performed a
      series of long-timescale molecular dynamics simulations to study how each of
      three key S. enterica lipid A modifications affect bilayer properties, with a
      focus on membrane structural characteristics, lateral interactions, and the
      divalent cation bridging network. Our results discern the unique impact each
      modification has on strengthening the bacterial outer membrane through effects
      such as increased hydrogen bonding and tighter lipid packing. Additionally, one
      of the modifications studied shifts Ca2+ from the lipid A region, replacing it as
      a major cross-linking agent between adjacent lipids and potentially making
      bacteria less susceptible to AMPs that competitively displace cations from the
      membrane surface. These results further improve our understanding of outer
      membrane chemical properties and help elucidate how outer membrane modification
      systems, such as PhoPQ in S. enterica, are able to alter bacterial virulence.

PMID- 29590597
TI  - The Antiparallel Dimerization of Myosin X Imparts Bundle Selectivity for
      Processive Motility.
AB  - Myosin X is an unconventional actin-based molecular motor involved in filopodial
      formation, microtubule-actin filament interaction, and cell migration. Myosin X
      is an important component of filopodia regulation, localizing to tips of growing
      filopodia by an unclear targeting mechanism. The native alpha-helical
      dimerization domain of myosin X is thought to associate with antiparallel
      polarity of the two amino acid chains, making myosin X the only myosin that is
      currently considered to form antiparallel dimers. This study aims to determine if
      antiparallel dimerization of myosin X imparts selectivity toward actin bundles by
      comparing the motility of parallel and antiparallel dimers of myosin X on single
      and fascin-bundled actin filaments. Antiparallel myosin X dimers exhibit
      selective processivity on fascin-bundled actin and are only weakly processive on
      single actin filaments below saturating [ATP]. Artificial forced parallel dimers
      of myosin X are robustly processive on both single and bundled actin, exhibiting
      no selectivity. To determine the relationship between gating of the reaction
      steps and observed differences in motility, a mathematical model was developed to
      correlate the parameters of motility with the biochemical and mechanical kinetics
      of the dimer. Results from the model, constrained by experimental data, suggest
      that the probability of binding forward, toward the barbed end of the actin
      filament, is lower in antiparallel myosin X on single actin filaments compared to
      fascin-actin bundles and compared to constructs of myosin X with parallel
      dimerization.

PMID- 29590598
TI  - Detailed Analyses of Stall Force Generation in Mycoplasma mobile Gliding.
AB  - Mycoplasma mobile is a bacterium that uses a unique mechanism to glide on solid
      surfaces at a velocity of up to 4.5 MUm/s. Its gliding machinery comprises
      hundreds of units that generate the force for gliding based on the energy derived
      from ATP; the units catch and pull sialylated oligosaccharides fixed to solid
      surfaces. In this study, we measured the stall force of wild-type and mutant
      strains of M. mobile carrying a bead manipulated using optical tweezers. The
      strains that had been enhanced for binding exhibited weaker stall forces than the
      wild-type strain, indicating that stall force is related to force generation
      rather than to binding. The stall force of the wild-type strain decreased
      linearly from 113 to 19 picoNewtons after the addition of 0-0.5 mM free
      sialyllactose (a sialylated oligosaccharide), with a decrease in the number of
      working units. After the addition of 0.5 mM sialyllactose, the cells carrying a
      bead loaded using optical tweezers exhibited stepwise movements with force
      increments. The force increments ranged from 1 to 2 picoNewtons. Considering the
      70-nm step size, this small-unit force may be explained by the large gear ratio
      involved in the M. mobile gliding machinery.

PMID- 29590599
TI  - Spatial Cytoskeleton Organization Supports Targeted Intracellular Transport.
AB  - The efficiency of intracellular cargo transport from specific sources to target
      locations is strongly dependent upon molecular motor-assisted motion along the
      cytoskeleton. Radial transport along microtubules and lateral transport along the
      filaments of the actin cortex underneath the cell membrane are characteristic for
      cells with a centrosome. The interplay between the specific cytoskeleton
      organization and the motor performance results in a spatially inhomogeneous
      intermittent search strategy. To analyze the efficiency of such intracellular
      search strategies, we formulate a random velocity model with intermittent arrest
      states. We evaluate efficiency in terms of mean first passage times for three
      different, frequently encountered intracellular transport tasks: 1) the narrow
      escape problem, which emerges during cargo transport to a synapse or other
      specific region of the cell membrane; 2) the reaction problem, which considers
      the binding time of two particles within the cell; and 3) the reaction-escape
      problem, which arises when cargo must be released at a synapse only after pairing
      with another particle. Our results indicate that cells are able to realize
      efficient search strategies for various intracellular transport tasks
      economically through a spatial cytoskeleton organization that involves only a
      narrow actin cortex rather than a cell body filled with randomly oriented actin
      filaments.

PMID- 29590600
TI  - Response of Single Cells to Shock Waves and Numerically Optimized Waveforms for
      Cancer Therapy.
AB  - Shock waves are used clinically for breaking kidney stones and treating
      musculoskeletal indications. The mechanisms by which shock waves interact with
      tissue are still not well understood. Here, ultra-high-speed imaging was used to
      visualize the deformation of individual cells embedded in a tissue-mimicking
      phantom when subject to shock-wave exposure from a clinical source. Three kidney
      epithelial cell lines were considered to represent normal healthy (human renal
      epithelial), cancer (CAKI-2), and virus-transformed (HK-2) cells. The
      experimental results showed that during the compressive phase of the shock waves,
      there was a small (<2%) decrease in the projected cell area, but during the
      tensile phase, there was a relatively large (~10%) increase in the projected cell
      area. The experimental observations were captured by a numerical model with a
      constitutive material framework consisting of an equation of state for the
      volumetric response and hyper-viscoelasticity for the deviatoric response. To
      model the volumetric cell response, it was necessary to change from a higher bulk
      modulus during the compression to a lower bulk modulus during the tensile shock
      loading. It was discovered that cancer cells showed a smaller deformation but
      faster response to the shock-wave tensile phase compared to their noncancerous
      counterparts. Cell viability experiments, however, showed that cancer cells
      suffered more damage than other cell types. These data suggest that the cell
      response to shock waves is specific to the type of cell and waveforms that could
      be tailored to an application. For example, the model predicts that a shock wave
      with a tensile stress of 4.59 MPa would increase cell membrane permeability for
      cancer cells with minimal impact on normal cells.

PMID- 29590601
TI  - Do Skeletal Dynamics Mediate Sugar Uptake and Transport in Human Erythrocytes?
AB  - We explore, herein, the hypothesis that transport of molecules or ions into
      erythrocytes may be affected and directly stimulated by the dynamics of the
      spectrin/actin skeleton. Skeleton/actin motions are driven by thermal
      fluctuations that may be influenced by ATP hydrolysis as well as by structural
      alterations of the junctional complexes that connect the skeleton to the cell's
      lipid membrane. Specifically, we focus on the uptake of glucose into erythrocytes
      via glucose transporter 1 and on the kinetics of glucose disassociation at the
      endofacial side of glucose transporter 1. We argue that glucose disassociation is
      affected by both hydrodynamic forces induced by the actin/spectrin skeleton and
      by probable contact of the swinging 37-nm-long F-actin protofilament with
      glucose, an effect we dub the "stickball effect." Our hypothesis and results are
      interpreted within the framework of the kinetic measurements and compartmental
      kinetic models of Carruthers and co-workers; these experimental results and
      models describe glucose disassociation as the "slow step" (i.e., rate-limiting
      step) in the uptake process. Our hypothesis is further supported by direct
      simulations of skeleton-enhanced transport using our molecular-based models for
      the actin/spectrin skeleton as well as by experimental measurements of glucose
      uptake into cells subject to shear deformations, which demonstrate the
      hydrodynamic effects of advection. Our simulations have, in fact, previously
      demonstrated enhanced skeletal dynamics in cells in shear deformations, as they
      occur naturally within the skeleton, which is an effect also supported by
      experimental observations.

PMID- 29590602
TI  - ECM Cross-Linking Regulates Invadopodia Dynamics.
AB  - Invadopodia are membrane protrusions dynamically assembled by invasive cancer
      cells in contact with the extracellular matrix (ECM). Invadopodia are enriched by
      the structural proteins actin and cortactin as well as metalloproteases such as
      MT1-MMP, whose function is to degrade the surrounding ECM. During metastasis,
      invadopodia are necessary for cancer cell intravasation and extravasation.
      Although signaling pathways involved in the assembly and function of invadopodia
      are well studied, few studies address invadopodia dynamics and how the cell-ECM
      interactions contribute to cell invasion. Using iterative analysis based on time
      lapse microscopy and mathematical modeling of invasive cancer cells, we found
      that cells oscillate between invadopodia presence and cell stasis-termed the
      "invadopodia state"-and invadopodia absence during cell translocation-termed the
      "migration state." Our data suggest that beta1-integrin-ECM binding and ECM cross
      linking control the duration of each of the two states. By changing the
      concentration of cross-linkers in two-dimensional and three-dimensional cultures,
      we generate an ECM in which 0-0.92 of total lysine residues are cross-linked.
      Using an ECM with a range of cross-linking degrees, we demonstrate that the
      dynamics of invadopodia-related functions have a biphasic relationship to ECM
      cross-linking. At intermediate levels of ECM cross-linking (0.39), cells exhibit
      rapid invadopodia protrusion-retraction cycles and rapid calcium spikes, which
      lead to more frequent MT1-MMP delivery, causing maximal invadopodia-mediated ECM
      degradation. In contrast, both extremely high or low levels of cross-linking lead
      to slower invadopodia-related dynamics and lower ECM degradation. Additionally,
      beta1-integrin inhibition modifies the dynamics of invadopodia-related functions
      as well as the length of time cells spend in either of the states. Collectively,
      these data suggest that beta1-integrin-ECM binding nonlinearly translates small
      physical differences in the extracellular environment to differences in the
      dynamics of cancer cell behaviors. Understanding the conditions under which
      invadopodia can be reduced by subtle environment-targeting treatments may lead to
      combination therapies for preventing metastatic spread.

PMID- 29590603
TI  - Gaussian Curvature Directs Stress Fiber Orientation and Cell Migration.
AB  - We show that substrates with nonzero Gaussian curvature influence the
      organization of stress fibers and direct the migration of cells. To study the
      role of Gaussian curvature, we developed a sphere-with-skirt surface in which a
      positive Gaussian curvature spherical cap is seamlessly surrounded by a negative
      Gaussian curvature draping skirt, both with principal radii similar to cell
      length scales. We find significant reconfiguration of two subpopulations of
      stress fibers when fibroblasts are exposed to these curvatures. Apical stress
      fibers in cells on skirts align in the radial direction and avoid bending by
      forming chords across the concave gap, whereas basal stress fibers bend along the
      convex direction. Cell migration is also strongly influenced by the Gaussian
      curvature. Real-time imaging shows that cells migrating on skirts repolarize to
      establish a leading edge in the azimuthal direction. Thereafter, they migrate in
      that direction. This behavior is notably different from migration on planar
      surfaces, in which cells typically migrate in the same direction as the apical
      stress fiber orientation. Thus, this platform reveals that nonzero Gaussian
      curvature not only affects the positioning of cells and alignment of stress fiber
      subpopulations but also directs migration in a manner fundamentally distinct from
      that of migration on planar surfaces.

PMID- 29590604
TI  - Tissue-Specific Optical Mapping Models of Swine Atria Informed by Optical
      Coherence Tomography.
AB  - Computational models and experimental optical mapping of cardiac
      electrophysiology serve as powerful tools to investigate the underlying
      mechanisms of arrhythmias. Modeling can also aid the interpretation of optical
      mapping signals, which may have different characteristics with respect to the
      underlying electrophysiological signals they represent. However, despite the
      prevalence of atrial arrhythmias such as atrial fibrillation, models of optical
      electrical mapping incorporating realistic structure of the atria are lacking.
      Therefore, we developed image-based models of atrial tissue using structural
      information extracted from optical coherence tomography (OCT), which can provide
      volumetric tissue characteristics in high resolution. OCT volumetric data of four
      swine atrial tissue samples were used to develop models incorporating tissue
      geometry, tissue-specific myofiber orientation, and ablation lesion regions. We
      demonstrated the use of these models through electrophysiology and photon
      scattering simulations. Changes in transmural electrical conduction were observed
      with the inclusion of OCT-derived, depth-resolved fiber orientation.
      Additionally, the amplitude of optical mapping signals were not found to
      correspond with lesion transmurality because of lesion geometry and electrical
      propagation occurring beyond excitation light penetration. This work established
      a framework for the development of tissue-specific models of atrial tissue
      derived from OCT imaging data, which can be useful in future investigations of
      electrophysiology and optical mapping signals with respect to realistic atrial
      tissue structure.

PMID- 29590605
TI  - Matrix Production and Sporulation in Bacillus subtilis Biofilms Localize to
      Propagating Wave Fronts.
AB  - Bacterial biofilms are surface-attached microbial communities encased in self
      produced extracellular polymeric substances. Here we demonstrate that during the
      development of Bacillus subtilis biofilms, matrix production is localized to an
      annular front propagating at the periphery and sporulation to a second front at a
      fixed distance at the interior. We show that within these fronts, cells switch
      off matrix production and transition to sporulation after a set time delay of
      ~100 min. Correlation analyses of fluctuations in fluorescence reporter activity
      reveal that the fronts emerge from a pair of gene-expression waves of matrix
      production and sporulation. The localized expression waves travel across cells
      that are immobilized in the biofilm matrix in contrast to active cell migration
      or horizontal colony spreading. Our results suggest that front propagation arises
      via a local developmental program occurring at the level of individual bacterial
      cells, likely driven by nutrient depletion and metabolic by-product accumulation.
      A single-length scale and timescale couples the spatiotemporal propagation of
      both fronts throughout development. As a result, gene expression patterns within
      the advancing fronts collapse to self-similar expression profiles. Our findings
      highlight the key role of the localized cellular developmental program associated
      with the propagating front in describing biofilm growth.

PMID- 29590606
TI  - A Nonquiescent "Idling" Population State in Drug-Treated, BRAF-Mutated Melanoma.
AB  - Targeted therapy is an effective standard of care in BRAF-mutated malignant
      melanoma. However, the duration of tumor remission varies unpredictably among
      patients, and relapse is almost inevitable. Here, we examine the responses of
      several BRAF-mutated melanoma cell lines (including isogenic subclones) to BRAF
      inhibitors. We observe complex response dynamics across cell lines, with short
      term responses (<100 h) varying from cell line to cell line. In the long term,
      however, we observe equilibration of all drug-treated populations into a
      nonquiescent state characterized by a balanced rate of death and division, which
      we term the "idling" state, and to our knowledge, this state has not been
      previously reported. Using mathematical modeling, we propose that the observed
      population-level dynamics are the result of cells transitioning between basins of
      attraction within a drug-modified phenotypic landscape. Each basin is associated
      with a drug-induced proliferation rate, a recently introduced metric of an
      antiproliferative drug effect. The idling population state represents a new
      dynamic equilibrium in which cells are distributed across the landscape such that
      the population achieves zero net growth. By fitting our model to experimental
      drug-response data, we infer the phenotypic landscapes of all considered melanoma
      cell lines and provide a unifying view of how BRAF-mutated melanomas respond to
      BRAF inhibition. We hypothesize that the residual disease observed in patients
      after targeted therapy is composed of a significant number of idling cells. Thus,
      defining molecular determinants of the phenotypic landscape that idling
      populations occupy may lead to "targeted landscaping" therapies based on rational
      modification of the landscape to favor basins with greater drug susceptibility.

PMID- 29590607
TI  - Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation.
AB  - CRISPR-Cas systems adapt their immunological memory against their invaders by
      integrating short DNA fragments into clustered regularly interspaced short
      palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery
      of the CRISPR integration process, various class I and II CRISPR-Cas systems
      encode Cas4 proteins for which the role is unknown. Here, we introduced the
      CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system
      of Synechocystis sp. 6803 into Escherichia coli and observed that cas4 is
      strictly required for the selection of targets with protospacer adjacent motifs
      (PAMs) conferring I-D CRISPR interference in the native host Synechocystis. We
      propose a model in which Cas4 assists the CRISPR adaptation complex Cas1-2 by
      providing DNA substrates tailored for the correct PAM. Introducing functional
      spacers that target DNA sequences with the correct PAM is key to successful
      CRISPR interference, providing a better chance of surviving infection by mobile
      genetic elements.

PMID- 29590608
TI  - The Murine Natural Cytotoxic Receptor NKp46/NCR1 Controls TRAIL Protein
      Expression in NK Cells and ILC1s.
AB  - TRAIL is an apoptosis-inducing ligand constitutively expressed on liver-resident
      type 1 innate lymphoid cells (ILC1s) and a subset of natural killer (NK) cells,
      where it contributes to NK cell anti-tumor, anti-viral, and immunoregulatory
      functions. However, the intrinsic pathways involved in TRAIL expression in ILCs
      remain unclear. Here, we demonstrate that the murine natural cytotoxic receptor
      mNKp46/NCR1, expressed on ILC1s and NK cells, controls TRAIL protein expression.
      Using NKp46-deficient mice, we show that ILC1s lack constitutive expression of
      TRAIL protein and that NK cells activated in vitro and in vivo fail to upregulate
      cell surface TRAIL in the absence of NKp46. We show that NKp46 regulates TRAIL
      expression in a dose-dependent manner and that the reintroduction of NKp46 in
      mature NK cells deficient for NKp46 is sufficient to restore TRAIL surface
      expression. These studies uncover a link between NKp46 and TRAIL expression in
      ILCs with potential implications in pathologies involving NKp46-expressing cells.

PMID- 29590609
TI  - Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer.
AB  - ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated
      genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear
      cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show
      that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in
      ovarian cancers. This correlated with enhanced growth suppression induced by the
      inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2
      in an ARID1A status-dependent manner. HDAC2 functions as a co-repressor of EZH2
      to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as
      PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth
      and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse
      models. This correlated with a significant improvement of survival of mice
      bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for
      repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers.

PMID- 29590610
TI  - A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF
      Deficiency in Prader-Willi Syndrome.
AB  - Transcriptional analysis of brain tissue from people with molecularly defined
      causes of obesity may highlight disease mechanisms and therapeutic targets. We
      performed RNA sequencing of hypothalamus from individuals with Prader-Willi
      syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia.
      We found that upregulated genes overlap with the transcriptome of mouse Agrp
      neurons that signal hunger, while downregulated genes overlap with the expression
      profile of Pomc neurons activated by feeding. Downregulated genes are expressed
      mainly in neuronal cells and contribute to neurogenesis, neurotransmitter
      release, and synaptic plasticity, while upregulated, predominantly microglial
      genes are involved in inflammatory responses. This transcriptional signature may
      be mediated by reduced brain-derived neurotrophic factor expression.
      Additionally, we implicate disruption of alternative splicing as a potential
      molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic
      analysis of the human hypothalamus may identify neural mechanisms involved in
      energy homeostasis and potential therapeutic targets for weight loss.

PMID- 29590611
TI  - Nicotinic Acetylcholine Receptors Control Encoding and Retrieval of Associative
      Recognition Memory through Plasticity in the Medial Prefrontal Cortex.
AB  - Nicotinic acetylcholine receptors (nAChRs) expressed in the medial prefrontal
      cortex have critical roles in cognitive function. However, whether nAChRs are
      required for associative recognition memory and the mechanisms by which nAChRs
      may contribute to mnemonic processing are not known. We demonstrate that nAChRs
      in the prefrontal cortex exhibit subtype-specific roles in associative memory
      encoding and retrieval. We present evidence that these separate roles of nAChRs
      may rely on bidirectional modulation of plasticity at synaptic inputs to the
      prefrontal cortex that are essential for associative recognition memory.

PMID- 29590612
TI  - A Conserved Circadian Function for the Neurofibromatosis 1 Gene.
AB  - Loss of the Neurofibromatosis 1 (Nf1) protein, neurofibromin, in Drosophila
      disrupts circadian rhythms of locomotor activity without impairing central clock
      function, suggesting effects downstream of the clock. However, the relevant
      cellular mechanisms are not known. Leveraging the discovery of output circuits
      for locomotor rhythms, we dissected cellular actions of neurofibromin in recently
      identified substrates. Herein, we show that neurofibromin affects the levels and
      cycling of calcium in multiple circadian peptidergic neurons. A prominent site of
      action is the pars intercerebralis (PI), the fly equivalent of the hypothalamus,
      with cell-autonomous effects of Nf1 in PI cells that secrete DH44. Nf1 interacts
      genetically with peptide signaling to affect circadian behavior. We extended
      these studies to mammals to demonstrate that mouse astrocytes exhibit a 24-hr
      rhythm of calcium levels, which is also attenuated by lack of neurofibromin.
      These findings establish a conserved role for neurofibromin in intracellular
      signaling rhythms within the nervous system.

PMID- 29590613
TI  - A Screen for Candidate Targets of Lysine Polyphosphorylation Uncovers a Conserved
      Network Implicated in Ribosome Biogenesis.
AB  - Polyphosphates (polyP) are chains of inorganic phosphates found in all cells.
      Previous work has implicated these chains in diverse functions, but the mechanism
      of action is unclear. A recent study reports that polyP can be non-enzymatically
      and covalently attached to lysine residues on yeast proteins Nsr1 and Top1. One
      question emerging from this work is whether so-called "polyphosphorylation" is
      unique to these proteins or instead functions as a global regulator akin to other
      lysine post-translational modifications. Here, we present the results of a screen
      for polyphosphorylated proteins in yeast. We uncovered 15 targets including a
      conserved network of proteins functioning in ribosome biogenesis. Multiple genes
      contribute to polyphosphorylation of targets by regulating polyP synthesis, and
      disruption of this synthesis results in translation defects as measured by
      polysome profiling. Finally, we identify 6 human proteins that can be modified by
      polyP, highlighting the therapeutic potential of manipulating polyphosphorylation
      in vivo.

PMID- 29590614
TI  - Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple
      Flavivirus Infections.
AB  - Although the outcome of flavivirus infection can vary from asymptomatic to
      lethal, environmental factors modulating disease severity are poorly defined.
      Here, we observed increased susceptibility of mice to severe West Nile (WNV),
      Dengue, and Zika virus infections after treatment with oral antibiotics (Abx)
      that depleted the gut microbiota. Abx treatment impaired the development of
      optimal T cell responses, with decreased levels of WNV-specific CD8+ T cells
      associated with increased infection and immunopathology. Abx treatments that
      resulted in enhanced WNV susceptibility generated changes in the overall
      structure of the gut bacterial community and in the abundance of specific
      bacterial taxa. As little as 3 days of treatment with ampicillin was sufficient
      to alter host immunity and WNV outcome. Our results identify oral Abx therapy as
      a potential environmental determinant of systemic viral disease, and they raise
      the possibility that perturbation of the gut microbiota may have deleterious
      consequences for subsequent flavivirus infections.

PMID- 29590615
TI  - Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends
      on Continuous Expression of FOXO1.
AB  - Immunity following an acutely resolved infection or the long-term equipoise of
      chronic viral infections often depends on the maintenance of antigen-specific
      CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain
      unclear. We show that active and continuous programming by FOXO1 is required for
      the functional maintenance of a memory population. Upon Foxo1 deletion following
      resolution of an infection, memory cells rapidly lost their characteristic gene
      expression, gradually declined in number, and were impaired in self-renewal. This
      was extended to chronic infections, as a loss of FOXO1 during a persistent viral
      infection led to a rapid decline of the TCF7 (a.k.a. TCF1)-expressing memory-like
      subset of CD8+ T cells. We further establish FOXO1 regulation as a characteristic
      of human memory CD8+ T cells. Overall, we show that the molecular and functional
      longevity of a memory T cell population is actively maintained by the
      transcription factor FOXO1.

PMID- 29590616
TI  - p53 in Bronchial Club Cells Facilitates Chronic Lung Inflammation by Promoting
      Senescence.
AB  - The tumor suppressor p53 limits tumorigenesis by inducing apoptosis, cell cycle
      arrest, and senescence. Although p53 is known to limit inflammation during tumor
      development, its role in regulating chronic lung inflammation is less well
      understood. To elucidate the function of airway epithelial p53 in such
      inflammation, we subjected genetically modified mice, whose bronchial epithelial
      club cells lack p53, to repetitive inhalations of lipopolysaccharide (LPS), an
      exposure that leads to severe chronic bronchitis and airway senescence in wild
      type mice. Surprisingly, the club cell p53 knockout mice exhibited reduced airway
      senescence and bronchitis in response to chronic LPS exposure and were
      significantly protected from global lung destruction. Furthermore,
      pharmacological elimination of senescent cells also protected wild-type mice from
      chronic LPS-induced bronchitis. Our results implicate p53 in induction of club
      cell senescence and correlate epithelial cell senescence of chronic airway
      inflammation and lung destruction.

PMID- 29590617
TI  - Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through
      Distinct DNA Damage- and Histone Methylation-Dependent Pathways.
AB  - Polycomb group (PcG) factors maintain facultative heterochromatin and mediate
      many important developmental and differentiation processes. EZH2, a PcG histone
      H3 lysine-27 methyltransferase, is repressed in senescent cells. We show here
      that downregulation of EZH2 promotes senescence through two distinct mechanisms.
      First, depletion of EZH2 in proliferating cells rapidly initiates a DNA damage
      response prior to a reduction in the levels of H3K27me3 marks. Second, the
      eventual loss of H3K27me3 induces p16 (CDKN2A) gene expression independent of DNA
      damage and potently activates genes of the senescence-associated secretory
      phenotype (SASP). The progressive depletion of H3K27me3 marks can be viewed as a
      molecular "timer" to provide a window during which cells can repair DNA damage.
      EZH2 is regulated transcriptionally by WNT and MYC signaling and
      posttranslationally by DNA damage-triggered protein turnover. These mechanisms
      provide insights into the processes that generate senescent cells during aging.

PMID- 29590618
TI  - Telomere Dysfunction Disturbs Macrophage Mitochondrial Metabolism and the NLRP3
      Inflammasome through the PGC-1alpha/TNFAIP3 Axis.
AB  - Immune and inflammation dysregulation have been associated with the aging process
      and contribute to age-related disorders, but the underlying mechanism remains
      elusive. Here, we employed late-generation Terc knockout (Terc-/-) mice to
      investigate the impact of telomere dysfunction on the host defense and function
      of innate immune cells. Terc-/- mice displayed exaggerated lung inflammation and
      increased mortality upon respiratory staphylococcal infection, although their
      pathogen-clearing capacity was uncompromised. Mechanistically, we found that
      telomere dysfunction caused macrophage mitochondrial abnormality, oxidative
      stress, and hyperactivation of the NLRP3 inflammasome. The ubiquitin-editing
      enzyme TNFAIP3, together with PGC-1alpha, was critically involved in the
      regulation of mitochondrial and inflammatory gene expression and essential for
      the homeostatic role of telomeres. Together, the study reveals a regulatory
      paradigm that connects telomeres to mitochondrial metabolism, innate immunity,
      and inflammation, shedding light on age-related pathologies.

PMID- 29590619
TI  - Serine Availability Influences Mitochondrial Dynamics and Function through Lipid
      Metabolism.
AB  - Cell proliferation can be dependent on the non-essential amino acid serine, and
      dietary restriction of serine inhibits tumor growth, but the underlying
      mechanisms remain incompletely understood. Using a metabolomics approach, we
      found that serine deprivation most predominantly impacts cellular acylcarnitine
      levels, a signature of altered mitochondrial function. Fuel utilization from
      fatty acid, glucose, and glutamine is affected by serine deprivation, as are
      mitochondrial morphological dynamics leading to increased fragmentation.
      Interestingly, these changes can occur independently of nucleotide and redox
      metabolism, two known major functions of serine. A lipidomics analysis revealed
      an overall decrease in ceramide levels. Importantly, supplementation of the lipid
      component of bovine serum or C16:0-ceramide could partially restore defects in
      cell proliferation and mitochondrial fragmentation induced by serine deprivation.
      Together, these data define a role for serine in supporting mitochondrial
      function and cell proliferation through ceramide metabolism.

PMID- 29590620
TI  - A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of
      Plasma Lipids at Wakening.
AB  - Many favorable metabolic effects have been attributed to thermogenic activity of
      brown adipose tissue (BAT). Yet, time of day has rarely been considered in this
      field of research. Here, we show that a diurnal rhythm in BAT activity regulates
      plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake
      by BAT that synchronized with the light/dark cycle. Highest uptake was found at
      the onset of the active period, which coincided with high lipoprotein lipase
      expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in
      BAT activity determined the rate at which lipids were cleared from the
      circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In
      mice as well as humans, postprandial lipid excursions were nearly absent at
      waking. We anticipate that diurnal BAT activity is an important factor to
      consider when studying the therapeutic potential of promoting BAT activity.

PMID- 29590621
TI  - Supra-barrel Distribution of Directional Tuning for Global Motion in the Mouse
      Somatosensory Cortex.
AB  - Rodents explore their environment with an array of whiskers, inducing complex
      patterns of whisker deflections. Cortical neuronal networks can extract global
      properties of tactile scenes. In the primary somatosensory cortex, the
      information relative to the global direction of a spatiotemporal sequence of
      whisker deflections can be extracted at the single neuron level. To further
      understand how the cortical network integrates multi-whisker inputs, we imaged
      and recorded the mouse barrel cortex activity evoked by sequences of multi
      whisker deflections generating global motions in different directions. A majority
      of barrel-related cortical columns show a direction preference for global motions
      with an overall preference for caudo-ventral directions. Responses to global
      motions being highly sublinear, the identity of the first deflected whiskers is
      highly salient but does not seem to determine the global direction preference.
      Our results further demonstrate that the global direction preference is spatially
      organized throughout the barrel cortex at a supra-columnar scale.

PMID- 29590622
TI  - Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in
      Cone Photoreceptor Cells and Visual Acuity.
AB  - In the vertebrate retina, cone photoreceptors play crucial roles in photopic
      vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells.
      However, the mechanisms underlying selective synapse formation in the cone
      photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a
      leucine-rich transmembrane protein, localizes to the photoreceptor synaptic
      terminal and regulates the synaptic connection between cone photoreceptors and
      cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of
      cone photoreceptor pedicles, as well as an impairment of signal transmission from
      cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that
      Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6,
      an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice
      showed visual acuity impairments in their optokinetic responses. These results
      suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation
      in cone photoreceptors and is essential for normal visual function.

PMID- 29590623
TI  - LRIT1 Modulates Adaptive Changes in Synaptic Communication of Cone
      Photoreceptors.
AB  - Cone photoreceptors scale dynamically the sensitivity of responses to maintain
      responsiveness across wide range of changes in luminance. Synaptic changes
      contribute to this adaptation, but how this process is coordinated at the
      molecular level is poorly understood. Here, we report that a cell adhesion-like
      molecule, LRIT1, is enriched selectively at cone photoreceptor synapses where it
      engages in a trans-synaptic interaction with mGluR6, the principal receptor in
      postsynaptic ON-bipolar cells. The levels of LRIT1 are regulated by the
      neurotransmitter release apparatus that controls photoreceptor output. Knockout
      of LRIT1 in mice increases the sensitivity of cone synaptic signaling while
      impairing its ability to adapt to background light without overtly influencing
      the morphology or molecular composition of photoreceptor synapses. Accordingly,
      mice lacking LRIT1 show visual deficits under conditions requiring temporally
      challenging discrimination of visual signals in steady background light. These
      observations reveal molecular mechanisms involved in scaling synaptic
      communication in the retina.

PMID- 29590624
TI  - Upregulation of Microglial ZEB1 Ameliorates Brain Damage after Acute Ischemic
      Stroke.
AB  - Microglia are a key immune-competent cell type that respond to environmental and
      physiological changes during ischemic stroke. However, the molecular mechanisms
      controlling post-ischemic microglia activity are unclear. Understanding these
      mechanisms may ultimately reduce disease burden and allow the manipulation of
      microglia responses to shape the outcomes of stroke. Here, we report that, after
      experimentally induced stroke, ZEB1 is highly expressed in ipsilateral cerebral
      hemisphere, where it is upregulated mainly in microglia. Using a conditional
      transgenic mouse, we found that ZEB1 upregulation in microglia regulates immune
      responses in the CNS and alleviates brain injury after ischemic stroke. Our data
      indicate that ZEB1 overexpression mediates microglia responses and, in turn,
      inhibits the production of astrocytic CXCL1 through the TGF-beta1-dependent
      pathway. Reduced CXCL1 leads to a decline in neutrophil infiltration into the
      brain, thereby reducing CNS inflammation. Our results demonstrate the importance
      of ZEB1 in microglia-orchestrated neuroinflammation and suggest a potential means
      for reducing stroke-induced neurological injury.

PMID- 29590625
TI  - Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in
      the Adult Mammalian CNS.
AB  - Reactive astrocytes influence post-injury recovery, repair, and pathogenesis of
      the mammalian CNS. Much of the regulation of astrocyte reactivity, however,
      remains to be understood. Using genetic loss and gain-of-function analyses in
      vivo, we show that the conserved MAP3K13 (also known as leucine zipper-bearing
      kinase [LZK]) promotes astrocyte reactivity and glial scar formation after CNS
      injury. Inducible LZK gene deletion in astrocytes of adult mice reduced
      astrogliosis and impaired glial scar formation, resulting in increased lesion
      size after spinal cord injury. Conversely, LZK overexpression in astrocytes
      enhanced astrogliosis and reduced lesion size. Remarkably, in the absence of
      injury, LZK overexpression alone induced widespread astrogliosis in the CNS and
      upregulated astrogliosis activators pSTAT3 and SOX9. The identification of LZK as
      a critical cell-intrinsic regulator of astrocyte reactivity expands our
      understanding of the multicellular response to CNS injury and disease, with broad
      translational implications for neural repair.

PMID- 29590626
TI  - DCC-Mediated Dab1 Phosphorylation Participates in the Multipolar-to-Bipolar
      Transition of Migrating Neurons.
AB  - Newborn neurons undergo inside-out migration to their final destinations during
      neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1
      (Dab1) is a critical mechanism controlling cortical neuron migration. However,
      the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we
      report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3
      domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232.
      Interestingly, knockdown of DCC or truncation of its P3 domain dramatically
      delays neuronal migration and impairs the multipolar-to-bipolar transition of
      migrating neurons. Notably, the migration delay and morphological transition
      defects are rescued by the expression of a phospho-mimetic Dab1 or a
      constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src
      family tyrosine kinases that effectively induces Dab1 phosphorylation.
      Collectively, these findings illustrate a DCC-Dab1 interaction that ensures
      proper neuronal migration during neocortical development.

PMID- 29590627
TI  - Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons
      through Overlapping but Distinct Pathways.
AB  - In Alzheimer's disease, neurofibrillary tangle pathology appears to spread along
      neuronal connections, proposed to be mediated by the release and uptake of
      abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is
      currently unclear whether transfer of tau between neurons is a toxic gain-of
      function process in dementia or reflects a constitutive biological process. We
      report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin
      dependent phase typical of endocytosis and a second, slower actin-dependent phase
      of macropinocytosis. Aggregated tau entry is independent of actin polymerization
      and largely dynamin dependent, consistent with endocytosis and distinct from
      macropinocytosis, the major route for aggregated tau entry reported for non
      neuronal cells. Anti-tau antibodies abrogate monomeric tau entry into neurons,
      but less efficiently in the case of aggregated tau, where internalized tau
      carries antibody with it into neurons. These data suggest that tau entry to human
      neurons is a physiological process and not a disease-specific phenomenon.

PMID- 29590628
TI  - Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary
      Fibrosis.
AB  - Fibroblast heterogeneity has long been recognized in mouse and human lungs,
      homeostasis, and disease states. However, there is no common consensus on
      fibroblast subtypes, lineages, biological properties, signaling, and plasticity,
      which severely hampers our understanding of the mechanisms of fibrosis. To
      comprehensively classify fibroblast populations in the lung using an unbiased
      approach, single-cell RNA sequencing was performed with mesenchymal preparations
      from either uninjured or bleomycin-treated mouse lungs. Single-cell transcriptome
      analyses classified and defined six mesenchymal cell types in normal lung and
      seven in fibrotic lung. Furthermore, delineation of their differentiation
      trajectory was achieved by a machine learning method. This collection of single
      cell transcriptomes and the distinct classification of fibroblast subsets provide
      a new resource for understanding the fibroblast landscape and the roles of
      fibroblasts in fibrotic diseases.

PMID- 29590629
TI  - Enhancer Activation by Pharmacologic Displacement of LSD1 from GFI1 Induces
      Differentiation in Acute Myeloid Leukemia.
AB  - Pharmacologic inhibition of LSD1 promotes blast cell differentiation in acute
      myeloid leukemia (AML) with MLL translocations. The assumption has been that
      differentiation is induced through blockade of LSD1's histone demethylase
      activity. However, we observed that rapid, extensive, drug-induced changes in
      transcription occurred without genome-wide accumulation of the histone
      modifications targeted for demethylation by LSD1 at sites of LSD1 binding and
      that a demethylase-defective mutant rescued LSD1 knockdown AML cells as
      efficiently as wild-type protein. Rather, LSD1 inhibitors disrupt the interaction
      of LSD1 and RCOR1 with the SNAG-domain transcription repressor GFI1, which is
      bound to a discrete set of enhancers located close to transcription factor genes
      that regulate myeloid differentiation. Physical separation of LSD1/RCOR1 from
      GFI1 is required for drug-induced differentiation. The consequent inactivation of
      GFI1 leads to increased enhancer histone acetylation within hours, which directly
      correlates with the upregulation of nearby subordinate genes.

PMID- 29590630
TI  - Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport
      Receptors.
AB  - Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered
      proteins, constituting the selective barrier of the nuclear pore complex (NPC).
      Previous studies showed that nuclear transport receptors (NTRs) were found to
      interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid
      formation and breakage of interactions with many individual FG motifs. Here, we
      use single-molecule studies combined with atomistic simulations to show that, in
      sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism
      when interacting with the export receptor CRM1. Association and dissociation rate
      constants are more than an order of magnitude lower than in the archetypal-fuzzy
      complex between FG-Nup153 and NTRs. Unexpectedly, this behavior appears not to be
      encoded selectively into CRM1 but rather into the FG-Nup214 sequence. The same
      distinct binding mechanisms are unperturbed in O-linked beta-N-acetylglucosamine
      modified FG-Nups. Our results have implications for differential roles of
      distinctly spatially distributed FG-Nup?NTR interactions in the cell.

PMID- 29590631
TI  - Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor
      for Meningioma Proliferation.
AB  - Meningioma is the most common primary intracranial tumor, but the molecular
      drivers of aggressive meningioma are incompletely understood. Using 280 human
      meningioma samples and RNA sequencing, immunohistochemistry, whole-exome
      sequencing, DNA methylation arrays, and targeted gene expression profiling, we
      comprehensively define the molecular profile of aggressive meningioma.
      Transcriptomic analyses identify FOXM1 as a key transcription factor for
      meningioma proliferation and a marker of poor clinical outcomes. Consistently, we
      discover genomic and epigenomic factors associated with FOXM1 activation in
      aggressive meningiomas. Finally, we define a FOXM1/Wnt signaling axis in
      meningioma that is associated with a mitotic gene expression program, poor
      clinical outcomes, and proliferation of primary meningioma cells. In summary, we
      find that multiple molecular mechanisms converge on a FOXM1/Wnt signaling axis in
      aggressive meningioma.

PMID- 29590632
TI  - Vitamin D deficiency in the ApcPirc/+ rat does not exacerbate colonic
      tumorigenesis, while low dietary calcium might be protective.
AB  - Human studies have shown that individuals with colon cancer tend to have lower
      serum 25-hydroxy-vitamin D3 [25(OH)D3] levels compared with healthy controls, but
      whether this link is causative, a result of the disease or an indicator of
      another factor altogether has yet to be demonstrated. In humans, vitamin D,
      calcium and UV exposure are inextricably linked; therefore, understanding the
      individual and combined roles of each of these will require animal models
      specifically designed to address these questions. To begin to untangle this
      network, our group has employed the ApcPirc/+ rat, which contains a truncating
      mutation in the Apc gene, leading to the development of colonic tumors. Our group
      previously utilized this model to demonstrate that vitamin D supplementation
      above normal does not reduce colonic tumor burden and, in fact, increased tumor
      multiplicity in a dose-dependent manner. In the current study, we tested whether
      vitamin D deficiency plays a causative role in tumor development using two
      strains which differ in their susceptibility to intestinal tumorigenesis. In the
      colon, vitamin D deficiency did not increase the development of tumors in either
      strain, and was actually protective in one strain. Unexpectedly, low dietary
      calcium combined with vitamin D deficiency significantly suppressed tumor
      development in the small intestine and colon of both strains. The vast majority
      of tumors in the human intestine occur in the colon, and we find no evidence to
      support a direct role of vitamin D deficiency in increasing colonic
      tumorigenesis, and low calcium might protect against tumor development.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 29590633
TI  - Disease Ontology: improving and unifying disease annotations across species.
AB  - Model organisms are vital to uncovering the mechanisms of human disease and
      developing new therapeutic tools. Researchers collecting and integrating relevant
      model organism and/or human data often apply disparate terminologies
      (vocabularies and ontologies), making comparisons and inferences difficult. A
      unified disease ontology is required that connects data annotated using diverse
      disease terminologies, and in which the terminology relationships are
      continuously maintained. The Mouse Genome Database (MGD,
      http://www.informatics.jax.org), Rat Genome Database (RGD, http://rgd.mcw.edu)
      and Disease Ontology (DO, http://www.disease-ontology.org) projects are
      collaborating to augment DO, aligning and incorporating disease terms used by MGD
      and RGD, and improving DO as a tool for unifying disease annotations across
      species. Coordinated assessment of MGD's and RGD's disease term annotations
      identified new terms that enhance DO's representation of human diseases.
      Expansion of DO term content and cross-references to clinical vocabularies (e.g.
      OMIM, ORDO, MeSH) has enriched the DO's domain coverage and utility for
      annotating many types of data generated from experimental and clinical
      investigations. The extension of anatomy-based DO classification structure of
      disease improves accessibility of terms and facilitates application of DO for
      computational research. A consistent representation of disease associations
      across data types from cellular to whole organism, generated from clinical and
      model organism studies, will promote the integration, mining and comparative
      analysis of these data. The coordinated enrichment of the DO and adoption of DO
      by MGD and RGD demonstrates DO's usability across human data, MGD, RGD and the
      rest of the model organism database community.

PMID- 29590634
TI  - Mek1Y130C mice recapitulate aspects of human cardio-facio-cutaneous syndrome.
AB  - The RAS/MAPK signaling pathway is one of the most investigated pathways, owing to
      its established role in numerous cellular processes and implication in cancer.
      Germline mutations in genes encoding members of the RAS/MAPK pathway also cause
      severe developmental syndromes collectively known as RASopathies. These syndromes
      share overlapping characteristics, including craniofacial dysmorphology, cardiac
      malformations, cutaneous abnormalities and developmental delay. Cardio-facio
      cutaneous syndrome (CFC) is a rare RASopathy associated with mutations in BRAF,
      KRAS, MEK1 (MAP2K1) and MEK2 (MAP2K2). MEK1 and MEK2 mutations are found in ~25%
      of the CFC patients and the MEK1Y130C substitution is the most common one.
      However, little is known about the origins and mechanisms responsible for the
      development of CFC. To our knowledge, no mouse model carrying RASopathy-linked
      Mek1 or Mek2 gene mutations has been reported. To investigate the molecular and
      developmental consequences of the Mek1Y130C mutation, we generated a mouse line
      carrying this mutation. Analysis of mice from a Mek1 allelic series revealed that
      the Mek1Y130C allele expresses both wild-type and Y130C mutant forms of MEK1.
      However, despite reduced levels of MEK1 protein and the lower abundance of MEK1
      Y130C protein than wild type, Mek1Y130C mutants showed increased ERK (MAPK)
      protein activation in response to growth factors, supporting a role for MEK1
      Y130C in hyperactivation of the RAS/MAPK pathway, leading to CFC. Mek1Y130C
      mutant mice exhibited pulmonary artery stenosis, cranial dysmorphia and
      neurological anomalies, including increased numbers of GFAP+ astrocytes and
      Olig2+ oligodendrocytes in regions of the cerebral cortex. These data indicate
      that the Mek1Y130C mutation recapitulates major aspects of CFC, providing a new
      animal model to investigate the physiopathology of this RASopathy. This article
      has an associated First Person interview with the first author of the paper.

PMID- 29590635
TI  - Identification of protective postexposure mycobacterial vaccine antigens using an
      immunosuppression-based reactivation model in the zebrafish.
AB  - Roughly one third of the human population carries a latent Mycobacterium
      tuberculosis infection, with a 5-10% lifetime risk of reactivation to active
      tuberculosis and further spreading the disease. The mechanisms leading to the
      reactivation of a latent Mycobacterium tuberculosis infection are insufficiently
      understood. Here, we used a natural fish pathogen, Mycobacterium marinum, to
      model the reactivation of a mycobacterial infection in the adult zebrafish (Danio
      rerio). A low-dose intraperitoneal injection (~40 colony-forming units) led to a
      latent infection, with mycobacteria found in well-organized granulomas surrounded
      by a thick layer of fibrous tissue. A latent infection could be reactivated by
      oral dexamethasone treatment, which led to disruption of the granuloma structures
      and dissemination of bacteria. This was associated with the depletion of
      lymphocytes, especially CD4+ T cells. Using this model, we verified that
      ethambutol is effective against an active disease but not a latent infection. In
      addition, we screened 15 mycobacterial antigens as postexposure DNA vaccines, of
      which RpfB and MMAR_4207 reduced bacterial burdens upon reactivation, as did the
      Ag85-ESAT-6 combination. In conclusion, the adult zebrafish-M. marinum infection
      model provides a feasible tool for examining the mechanisms of reactivation in
      mycobacterial infections, and for screening vaccine and drug candidates.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 29590636
TI  - Vangl2 disruption alters the biomechanics of late spinal neurulation leading to
      spina bifida in mouse embryos.
AB  - Human mutations in the planar cell polarity component VANGL2 are associated with
      the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents
      initiation of neural tube closure, precluding analysis of its subsequent roles in
      neurulation. Spinal neurulation involves rostral-to-caudal 'zippering' until
      completion of closure is imminent, when a caudal-to-rostral closure point,
      'Closure 5', arises at the caudal-most extremity of the posterior neuropore
      (PNP). Here, we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE)
      throughout neurulation and in an increasing proportion of PNP neuroepithelial
      cells at late neurulation stages. This deletion impaired PNP closure after the
      ~25-somite stage and resulted in caudal spina bifida in 67% of
      Grhl3Cre/+Vangl2Fl/Fl embryos. In the dorsal SE, Vangl2 deletion diminished
      rostrocaudal cell body orientation, but not directional polarisation of cell
      divisions. In the PNP, Vangl2 disruption diminished mediolateral polarisation of
      apical neuroepithelial F-actin profiles and resulted in eversion of the caudal
      PNP. This eversion prevented elevation of the caudal PNP neural folds, which in
      control embryos is associated with formation of Closure 5 around the 25-somite
      stage. Closure 5 formation in control embryos is associated with a reduction in
      mechanical stress withstood at the main zippering point, as inferred from the
      magnitude of neural fold separation following zippering point laser ablation.
      This stress accommodation did not happen in Vangl2-disrupted embryos. Thus,
      disruption of Vangl2-dependent planar-polarised processes in the PNP
      neuroepithelium and SE preclude zippering point biomechanical accommodation
      associated with Closure 5 formation at the completion of PNP closure.

PMID- 29590637
TI  - The role of the microRNA-146a/complement factor H/interleukin-1beta-mediated
      inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe
      epilepsy.
AB  - Increasing evidence indicates that neuroinflammation plays a crucial role in the
      pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the
      perpetuate inflammation develops. Some recent studies have suggested the possible
      involvement of microRNA-146a (miR-146a) in the modulation of inflammatory
      signaling occurring in TLE. To understand how miR-146a modulates inflammatory
      signaling in TLE, we investigated the role of interleukin-1beta (IL-1beta), miR
      146a and human complement factor H (CFH) in the perpetuate inflammation in rat
      models of chronic TLE and U251 cells. We found that enhancive miR-146a could
      upregulate the expression of IL-1beta and downregulate the expression of CFH,
      whereas reductive miR-146a could downregulate the expression of IL-1beta and
      upregulate the expression of CFH, in hippocampi of chronic TLE rat models.
      Meanwhile, enhancive miR-146a could increase the abnormal wave forms in the
      chronic TLE rat models. Additionally, enhancive IL-1beta could feedback
      downregulate the expression of CFH, upregulate the expression of miR-146a and
      increase the abnormal wave forms in chronic TLE rat models. After CFH gene
      knockdown in U251 cells, enhancive miR-146a did not upregulate the expression of
      IL-1beta. In summary, this study shows that enhancive miR-146a can upregulate the
      inflammatory factor IL-1beta in chronic TLE by downregulating CFH, and that
      upregulation of IL-1beta plays an important feedback-regulating role in the
      expression of miR-146a and CFH, forming a miR-146a-CFH-IL-1beta loop circuit that
      initiates a cascade of inflammation and then leads to the perpetuate inflammation
      in TLE. Therefore, modulation of the miR-146a-CFH-IL-1beta loop circuit could be
      a novel therapeutic target for TLE.

PMID- 29590638
TI  - Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial
      disease model.
AB  - Mitochondrial diseases are associated with a wide variety of clinical symptoms
      and variable degrees of severity. Patients with such diseases generally have a
      poor prognosis and often an early fatal disease outcome. With an incidence of 1
      in 5000 live births and no curative treatments available, relevant animal models
      to evaluate new therapeutic regimes for mitochondrial diseases are urgently
      needed. By knocking down ND-18, the unique Drosophila ortholog of NDUFS4, an
      accessory subunit of the NADH:ubiquinone oxidoreductase (Complex I), we developed
      and characterized several dNDUFS4 models that recapitulate key features of
      mitochondrial disease. Like in humans, the dNDUFS4 KD flies display severe
      feeding difficulties, an aspect of mitochondrial disorders that has so far been
      largely ignored in animal models. The impact of this finding, and an approach to
      overcome it, will be discussed in the context of interpreting disease model
      characterization and intervention studies.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29590639
TI  - Neutrophil-specific knockout demonstrates a role for mitochondria in regulating
      neutrophil motility in zebrafish.
AB  - Neutrophils are fast-moving cells essential for host immune functions. Although
      they primarily rely on glycolysis for ATP, isolated primary human neutrophils
      depend on mitochondrial membrane potential for chemotaxis. However, it is not
      known whether mitochondria regulate neutrophil motility in vivo, and the
      underlying molecular mechanisms remain obscure. Here, we visualized mitochondria
      in an interconnected network that localizes to the front and rear of migrating
      neutrophils using a novel transgenic zebrafish line. To disrupt mitochondrial
      function genetically, we established a gateway system harboring the CRISPR/Cas9
      elements for tissue-specific knockout. In a transgenic line, neutrophil-specific
      disruption of mitochondrial DNA polymerase, polg, significantly reduced the
      velocity of neutrophil interstitial migration. In addition, inhibiting the
      mitochondrial electron transport chain or the enzymes that reduce mitochondrial
      reactive oxygen species also inhibited neutrophil motility. The reduced cell
      motility that resulted from neutrophil-specific knockout of sod1 was rescued with
      sod1 mRNA overexpression, or by treating with scavengers of reactive oxygen
      species. Together, our work has provided the first in vivo evidence that
      mitochondria regulate neutrophil motility, as well as tools for the functional
      characterization of mitochondria-related genes in neutrophils and insights into
      immune deficiency seen in patients with primary mitochondrial disorders.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 29590640
TI  - Intestinal epithelial cell polarity defects in disease: lessons from microvillus
      inclusion disease.
AB  - The intestinal epithelium is a highly organized tissue. The establishment of
      epithelial cell polarity, with distinct apical and basolateral plasma membrane
      domains, is pivotal for both barrier formation and for the uptake and vectorial
      transport of nutrients. The establishment of cell polarity requires a specialized
      subcellular machinery to transport and recycle proteins to their appropriate
      location. In order to understand and treat polarity-associated diseases, it is
      necessary to understand epithelial cell-specific trafficking mechanisms. In this
      Review, we focus on cell polarity in the adult mammalian intestine. We discuss
      how intestinal epithelial polarity is established and maintained, and how
      disturbances in the trafficking machinery can lead to a polarity-associated
      disorder, microvillus inclusion disease (MVID). Furthermore, we discuss the
      recent developments in studying MVID, including the creation of genetically
      manipulated cell lines, mouse models and intestinal organoids, and their uses in
      basic and applied research.

PMID- 29590643
TI  - Disease Models & Mechanisms 2018: keeping you in the picture.

PMID- 29590641
TI  - Gastroenteropancreatic neuroendocrine neoplasms: genes, therapies and models.
AB  - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) refer to a group of
      heterogeneous cancers of neuroendocrine cell phenotype that mainly fall into one
      of two subtypes: gastroenteropancreatic neuroendocrine tumors (GEP-NETs; well
      differentiated) or gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs;
      poorly differentiated). Although originally defined as orphan cancers, their
      steadily increasing incidence highlights the need to better understand their
      etiology. Accumulating epidemiological and clinical data have shed light on the
      pathological characteristics of these diseases. However, the relatively low
      number of patients has hampered conducting large-scale clinical trials and hence
      the development of novel treatment strategies. To overcome this limitation,
      tractable disease models that faithfully reflect clinical features of these
      diseases are needed. In this Review, we summarize the current understanding of
      the genetics and biology of these diseases based on conventional disease models,
      such as genetically engineered mouse models (GEMMs) and cell lines, and discuss
      the phenotypic differences between the models and affected humans. We also
      highlight the emerging disease models derived from human clinical samples,
      including patient-derived xenograft models and organoids, which may provide
      biological and therapeutic insights into GEP-NENs.

PMID- 29590644
TI  - Acetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth.
AB  - BACKGROUND/AIMS: GATA4, a protein related to osteoblast differentiation and
      mineralization, whose acetylation is essential for cardiac defects. Here, we
      aimed to explore the functional impacts of GATA4 acetylation on osteoporosis
      (OS). METHODS: GATA4 acetylation in hFOB1.19 and 293T cells was detected after
      exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted
      to determine which HATs and HDACs was involved in the modulation of GATA4
      acetylation/deacetylation, and to identify the acetylation site. The
      transcriptional activity of GATA4 was measured in the presence or absence of
      cycloheximide. Furthermore, hFOB1.19 cells viability and apoptosis were evaluated
      after transfection with acetylation-defective mutant of GATA4. RESULTS: As a
      result, GATA4 acetylation was identified as a pivotal event in hFOB1.19 cells.
      GATA4 can be acetylated by P300/CBP, and the acetylation site was on lysine
      residue K313. Besides, the acetylation of GATA4 can be impaired by HDAC1, rather
      than by HDAC2-5. GATA4 acetylation contributed to the stability and transcription
      of GATA4. Moreover, GATA4 acetylation activated CCND2 transcription, and mutation
      of GATA4 on K-313 reduced cell viability and increased a mitochondria-dependent
      apoptosis in hFOB1.19 cells. CONCLUSION: Our data suggest that GATA4 exists as an
      acetylated protein in hFOB1.19 cells. Acetylation regulates the stability and
      transcription of GATA4, and activates CCND2 transcription, which may explain the
      growth-promoting functions of GATA4 in hFOB1.19 cells.

PMID- 29590642
TI  - Use of zebrafish to study Shigella infection.
AB  - Shigella is a leading cause of dysentery worldwide, responsible for up to 165
      million cases of shigellosis each year. Shigella is also recognised as an
      exceptional model pathogen to study key issues in cell biology and innate
      immunity. Several infection models have been useful to explore Shigella biology;
      however, we still lack information regarding the events taking place during the
      Shigella infection process in vivo Here, we discuss a selection of mechanistic
      insights recently gained from studying Shigella infection of zebrafish (Danio
      rerio), with a focus on cytoskeleton rearrangements and cellular immunity. We
      also discuss how infection of zebrafish can be used to investigate new concepts
      underlying infection control, including emergency granulopoiesis and the use of
      predatory bacteria to combat antimicrobial resistance. Collectively, these
      insights illustrate how Shigella infection of zebrafish can provide fundamental
      advances in our understanding of bacterial pathogenesis and vertebrate host
      defence. This information should also provide vital clues for the discovery of
      new therapeutic strategies against infectious disease in humans.

PMID- 29590645
TI  - PKCepsilon Increases Extracellular Elastin and Fibulin-5/DANCE in Dermal
      Fibroblasts.
AB  - BACKGROUND/AIMS: In the earlier study, the selective PKCepsilon activator DCP-LA
      increased elastic fibres in the dermis of HR-1 hairless mice. As a process of
      elastic fibre formation, tropoelastin, an elastin monomer, is secreted into the
      extracellular space. Secreted tropoelastin is delivered to the microfibrils by
      fibulin-5/developmental arteries and neural crest epidermal growth factor-like
      (DANCE) and undergoes self-association. Then, tropoelastin assembles around the
      microfibrils, growing into elastin and elastic fibres by lysyl oxidase (LOX)- or
      LOX-like (LOXL)-mediated cross-linking. The present study was conducted to
      understand the mechanism underlying DCP-LA-induced increase in elastin/elastic
      fibre. METHODS: Western blotting, immunocytochemistory, and real-time reverse
      transcription-polymerase chain reaction (RT-PCR) were carried out in cultured
      human dermal fibroblasts. PKCepsilon, mammalian target of rapamycin complex
      (mTOR), and p70 S6 kinase (S6K) were knocked-down by transfecting each siRNA.
      RESULTS: DCP-LA increased elastin and fibulin-5/DANCE in a treatment time (6-24
      h)- and a bell-shaped concentration (1 nM-1 uM)-dependent manner in the culture
      medium of human dermal fibroblasts. DCP-LA markedly increased elastic fibres in
      the extracellular space of cultured fibroblasts. DCP-LA-induced increase in
      extracellular elastin and fibulin-5/DANCE was abolished by a PKC inhibitor or
      knocking-down PKCepsilon. DCP-LA did not affect expression of mRNAs for
      tropoelastin and fiblin-5/DANCE in cultured fibroblasts. DCP-LA-induced increase
      in extracellular elastin and fibulin-5/DANCE was not inhibited by the protein
      synthesis inhibitor cycloheximide or by knocking-down mTOR and S6K. DCP-LA never
      increased extracellular elastin in the presence of elastase, that breaks down
      elastin. An inhibitor of matrix metalloproteinase 9, that degrades multiple
      extracellular matrix components including elastin, had no effect on the basal
      levels and the DCP-LA-induced increase levels of extracellular elastin.
      CONCLUSION: The results of the present study indicate that PKCepsilon, activated
      by DCP-LA, increases elastin and fibulin-5/DANCE in the extracellular space of
      cultured fibroblasts by the mechanism independent of transcriptional and
      translational modulation or inhibition of elastolysis.

PMID- 29590646
TI  - Human Glioblastoma-Derived Mesenchymal Stem Cell to Pericytes Transition and
      Angiogenic Capacity in Glioblastoma Microenvironment.
AB  - BACKGROUND/AIMS: Tumor vascular formation and maintenance are crucial events in
      glioblastoma development. Mesenchymal stem cells (MSCs) have been shown to
      differentiate into pericytes and contribute to neovascularization in the glioma
      microenvironment. Moreover, glioblastoma-derived mesenchymal stem cells (gb
      MSCs), which consist of CD90-MSCs and CD90+MSCs, are a subpopulation of MSCs that
      are more active in glioma vascularization. However, the functions of gb-MSCs and
      the microRNA (miRNA) modifications in the glioblastoma microenvironment have not
      yet been fully elucidated. Here, we focus on the pericyte differentiation
      potential of gb-MSCs and miRNA modifications in gb-MSCs during new vascular
      formation and glioblastoma growth. METHODS: In vitro, surface markers of gb-MSCs
      were detected by flow cytometry; the differentiation potential was evaluated by
      Oil Red O staining, Alizarin Red staining and Alcian blue staining; the
      proliferation and migration of gb-MSCs in different conditioned media were
      analyzed by the cck8 test and wound-healing assay, respectively; gb-MSC to
      pericyte transition was detected by immunofluorescence staining and western blot
      assay; angiogenetic capacity was analyzed by tube formation assay; and levels of
      cytokines in different supernatant were determined by ELISA. Additionally, RNA
      was isolated from gb-MSCs, and miRNA modifications were analyzed using the
      RAffymetrix miRNA microarray Results: We showed that glioblastoma-conditioned
      medium increased gb-MSC proliferation and migration and was capable of inducing
      gb-MSC differentiation into pericytes. Glioblastoma secreted angiogenic factors
      and gb-MSCs incubated in malignant glioblastoma-conditioned medium formed more
      tube-like structures, and these cells also adhered to tube-like vessels formed by
      human umbilical vein endothelial cells (HUVECs) on Matrigel to maintain tumor
      vascular structure in vitro. miRNA expression were also modified in gb-MSCs
      cultured in malignant glioblastoma-conditioned medium in vitro. CONCLUSION: These
      results provide new insight into the functional effects of a subpopulation of
      MSCs in glioblastoma and may help in the development of novel therapies for solid
      tumors.

PMID- 29590647
TI  - MiR-142-3p Inhibits TGF-beta3-Induced Blood-Testis Barrier Impairment by
      Targeting Lethal Giant Larvae Homolog 2.
AB  - BACKGROUND/AIMS: Transforming growth factor-beta3 (TGF-beta3) has been proved to
      perturb the blood-testis barrier (BTB) by accelerating junction protein
      endocytosis in Sertoli cells (SCs) to accommodate the traversing of preleptotene
      spermatocytes across the BTB around stage VIII in rat. Yet the molecular network
      underlying the impairment of TGF-beta3 on BTB integrity is not fully elucidated.
      Our study herein was designed to investigate the participation of microRNA-142-3p
      (miR-142-3p), which has been reported to affect TGF-beta3 signaling via different
      pathways, during BTB dynamics and the corresponding mechanisms. METHODS: MiRNA
      mimic or agomiRNA was co-administered with or without TGF-beta3 in the cultured
      SCs or in the rat testis. The SC permeability barrier function was reflected by
      measuring the transepithelial resistance (TER) and the permeability of the sodium
      fluorescein (Na-F). The BTB integrity was detected by the permeation of biotin. A
      luciferase reporter assay was used to testify the potential target of miR-142-3p,
      lethal giant larvae 2 (Lgl2). Laser capture microdissection (LCM) was applied to
      acquire cell components of different stages of seminiferious tubules, followed by
      detection of the expression levels of miR-142-3p, TGF-beta3, and Lgl2 by qPCR.
      The SC barrier function was also detected as above in the presence of TGF-beta3
      after Lgl2 knockdown. RESULTS: We revealed a reversion of TGF-beta3-induced BTB
      impairment after miR-142-3p treatment both in vitro and in vivo. Meanwhile, the
      activation of Cdc42 and reduction in occludin aroused by TGF-beta3 were also
      reversed by miR-142-3p. The predicted binding of miR-142-3p with 3'-untranslated
      region (3'-UTR) of Lgl2, was verified by the luciferase assay. Moreover, an
      increased Lgl2 level in TGF-beta3-treated SCs was found and correlated stage
      specific expressions of TGF-beta3, miR-142-3p, and Lgl2 were revealed. Knockdown
      of Lgl2 in SCs was shown to partially antagonize the BTB disruption mediated by
      TGF-beta3. CONCLUSIONS: Collectively, our results suggest a resistance of miR-142
      3p on the BTB impairment caused by TGF-beta3 during the seminiferous epithelial
      cycle by targeting Lgl2.

PMID- 29590648
TI  - Calcium/Calmodulin-Dependent Protein Kinase IV Mediates IFN-gamma-Induced Immune
      Behaviors in Skeletal Muscle Cells.
AB  - BACKGROUND/AIMS: Whether calcium/calmodulin-dependent protein kinase IV (CaMKIV)
      plays a role in regulating immunologic features of muscle cells in inflammatory
      environment, as it does for immune cells, remains mostly unknown. In this study,
      we investigated the influence of endogenous CaMKIV on the immunological
      characteristics of myoblasts and myotubes received IFN-gamma stimulation.
      METHODS: C2C12 and murine myogenic precursor cells (MPCs) were cultured and
      differentiated in vitro, in the presence of pro-inflammatory IFN-gamma. CaMKIV
      shRNA lentivirus transfection was performed to knockdown CaMKIV gene in C2C12
      cells. pEGFP-N1-CaMKIV plasmid was delivered into knockout cells for recovering
      intracellular CaMKIV gene level. CREB1 antagonist KG-501 was used to block CREB
      signal. qPCR, immunoblot analysis, or immunofluorescence was used to detect mRNA
      and protein levels of CaMKIV, immuno-molecules, or pro-inflammatory cytokines and
      chemokines. Co-stimulatory molecules expression was assessed by FACS analysis.
      RESULTS: IFN-gamma induces the expression or up-regulation of MHC-I/II and TLR3,
      and the up-regulation of CaMKIV level in muscle cells. In contrast, CaMKIV
      knockdown in myoblasts and myotubes leads to expression inhibition of the above
      immuno-molecules. As well, CaMKIV knockdown selectively inhibits pro-inflammatory
      cytokines/chemokines, and co-stimulatory molecules expression in IFN-gamma
      treated myoblasts and myotubes. Finally, CaMKIV knockdown abolishes IFN-gamma
      induced CREB pathway molecules accumulation in differentiated myotubes.
      CONCLUSIONS: CaMKIV can be induced to up-regulate in muscle cells under
      inflammatory condition, and positively mediates intrinsic immune behaviors of
      muscle cells triggered by IFN-gamma.

PMID- 29590649
TI  - Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes
      Influencing Glucose Metabolism and Islet beta-Cell Function.
AB  - BACKGROUND/AIMS: The islet is an important endocrine organ to secrete insulin to
      regulate the metabolism of glucose and maintain the stability of blood glucose.
      Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions
      and play key roles in many diseases, including type 2 diabetes (T2D). The aim of
      this study was to determine whether lncRNA-p3134 is associated with glucose
      metabolism and insulin signaling in pancreatic beta cells. METHODS: LncRNA
      microarray technology was used to identify the differentially expressed
      circulating lncRNAs in T2D patients. RT-PCR analyses were performed to determine
      the expression of lncRNA-p3134 in 30 pairs of diabetic and non-diabetic patients.
      The correlation of lncRNA-p3134 to clinical data from T2D patients was analyzed.
      LncRNA-p3134 was overexpressed in Min6 cells and db/db mice by adenovirus
      mediated technology. CCK-8, TUNEL, Western blot, glucose-stimulated insulin
      secretion (GSIS), ELISAs and immunochemistry were performed to determine the
      effect of lncRNA-p3134 on proliferation, apoptosis and insulin secretion both in
      vitro and vivo. RESULTS: The circulating level of lncRNA-p3134 was higher in
      diabetic patients than in non-diabetic controls and was correlated with fasting
      blood glucose and HOMA-beta levels. The lncRNA-p3134 had risen by 4 times in
      serum exosomes but nearly unchanged in exosome-free samples. The secretion of
      lncRNA-p3134 was dynamically modulated by glucose in both Min6 cells and isolated
      mouse islet cells. LncRNA-p3134 positively regulate GSIS through promoting of key
      regulators (Pdx-1, MafA, GLUT2 and Tcf7l2) in beta cells. In addition, the
      overexpression of lncRNA-p3134 resulted in a decreased apoptosis ratio and
      partially reversed the glucotoxicity effects on GSIS function in Min6 cells. The
      restoration of insulin synthesis and secretion the increase of the insulin
      positive cells areas by upregulation of lncRNA-p3134 in db/db mice confirmed the
      compensatory role of lncRNA-p3134 to preserve beta-cell function. Furthermore, a
      protective effect of lncRNA-p3134 on GSIS by positive modulation of PI3K/Akt/mTOR
      signaling was also confirmed. After blocking the PI3K/AKT signals with their
      specific inhibitor, the effect of overexpressed lncRNA-p3134 on insulin secretion
      was obviously attenuated. CONCLUSION: Taken together, the results of this study
      provide new insights into lncRNA-p3134 regulation in pancreatic beta cells and
      provide a better understanding of novel mechanism of glucose homeostasis.

PMID- 29590650
TI  - MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by
      Targeting CDC25B.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) play a crucial role in erythropoiesis. MiR
      23a~27a~24-2 clusters have been proven to take part in erythropoiesis via some
      proteins. CDC25B (cell division control Cdc2 phosphostase B) is also the target
      of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown.
      METHODS: To evaluate the potential role of miR-27a during erythroid
      differentiation, we performed miR-27a gain- and loss-of-function experiments on
      hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation
      at different time points. At the same time, the gamma-globin gene also was
      measured via real-time PCR. According to the results of the chips, we screened
      the target protein of miR-27a through a dual-luciferase reporter assay and
      identified it via Western blot analyses. To evaluate the function of CDC25B,
      benzidine staining and flow cytometry were employed to detect the cell
      differentiation and cell cycle. RESULTS: We found that miR-27a promotes hemin
      induced erythroid differentiation of human K562 cells by targeting cell division
      cycle 25 B (CDC25B). Overexpression of miR-27a promotes the differentiation of
      hemin-induced K562 cells, as demonstrated by gamma-globin overexpression. The
      inhibition of miR-27a expression suppresses erythroid differentiation, thus
      leading to a reduction in the gamma-globin gene. CDC25B was identified as a new
      target of miR-27a during erythroid differentiation. Overexpression of miR-27a led
      to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated
      when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B
      affected erythroid differentiation, as assessed by gamma-globin expression.
      CONCLUSION: This study is the first report of the interaction between miR-27a and
      CDC25B, and it improves the understanding of miRNA functions during erythroid
      differentiation.

PMID- 29590651
TI  - The Frequency of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Children
      with Asthma.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second-most
      frequent drug type to cause hypersensitivity reactions in children. Asthma is one
      of the risk factors for NSAID hypersensitivity (NSAID-H) in adult patients. There
      are limited number of studies evaluating NSAID-H among children with asthma. Our
      aim was to assess the frequency of confirmed NSAID-H and evaluate the
      classification of NSAID-H in children with asthma. METHODS: Patients followed
      with a diagnosis of asthma in our Pediatric Allergy Clinic were evaluated for
      NSAID-H. Patients were questioned whether they had used NSAIDs, and if they
      experienced any reaction with these drugs. A control group was also questioned
      for reactions to NSAID use. RESULTS: 976 children with asthma and 2,000 healthy
      children as a control group were included in this study. The mean age of the
      patients with asthma was 10.61 +/- 4.21 years and 59.5% were male. Ten (1%) had a
      reaction history to NSAIDs. NSAID-H was confirmed in 9 (0.9%) who were tested
      with the suspected drugs. Six of these were classified as "single NSAID-induced
      urticaria/angioedema or anaphylaxis" and 3 were classified as "NSAIDs-exacerbated
      respiratory disease." In the control group, only 1 subject had a reaction history
      to acetylsalicylic acid and no reaction developed in the provocation test.
      CONCLUSIONS: In our study, NSAID-H was found more frequent in children with
      asthma than in the control group. Children with asthma should be evaluated for
      reactions to NSAIDs during hospital visits.

PMID- 29590652
TI  - A Novel Device for Placement of a Secondary Tracheoesophageal Voice Prosthesis: A
      Preliminary Feasibility Study.
AB  - BACKGROUND: Tracheoesophageal puncture (TEP) for post-laryngectomy speech
      rehabilitation can be performed at the time of laryngectomy (primary) or at a
      subsequent time (secondary). Traditionally, the secondary procedure is performed
      using a rigid esophagoscope. Diseases like esophageal stricture, limited neck
      extension, and soft-tissue fibrosis can make this procedure technically
      challenging or impossible. We developed a novel device to perform a secondary
      tracheoesophageal puncture using a flexible esophagoscope. OBJECTIVE: To test the
      feasibility of a novel device used to create a secondary TEP in post-laryngectomy
      cadavers. METHODS: In this study, we performed a total laryngectomy on 3 fresh
      cadavers to establish the feasibility of our prototype. In each cadaver, a
      flexible esophagoscope was passed into the pharynx with the prototype. The
      prototype was passed through a working port and deployed to distend the
      esophagus. The puncture was visualized and a wire was passed via the newly
      established fistula. The device was activated, securing the wire, and then the
      esophagoscope and device were removed. RESULTS: There was 100% successful
      deployment of the prototype device, allowing rapid creation of the puncture and
      security of the guide wire in each cadaver. There was no evidence of collateral
      mucosal injury or esophageal perforation. CONCLUSIONS: The prototype device
      offers an alternative method to safely and efficiently perform a secondary TEP
      without the requirement of rigid esophagoscopy which can sometimes be technically
      impossible in this patient population.

PMID- 29590653
TI  - Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross
      Reactive Carbohydrate Determinants.
AB  - BACKGROUND: It has been suggested that latex-specific IgE analysis may lead to
      false-positive results, especially in patients with pollen allergy. In the
      present study, the reasons underlying clinically irrelevant latex-specific IgE
      positivity were investigated. METHODS: Thirty patients with latex allergy (group
      1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy
      individuals without allergy (group 2b) were enrolled. Participants from all 3
      groups were subjected to skin prick tests with aeroallergens including latex,
      latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex.
      All cases demonstrating positive latex-specific IgE also underwent specific IgE
      tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid
      transfer protein, and pineapple bromelain as cross-reactive carbohydrate
      determinants. RESULTS: Comparison of the atopic and healthy control groups showed
      that the rate of positive latex-specific IgE was significantly higher in group
      2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were
      remarkably higher in group 2a. CONCLUSION: False positivity to latex-specific IgE
      in ImmunoCAP analysis may be observed in approximately 19% of patients with
      pollen allergy. Profilins and bromelain are the main contributors to clinically
      irrelevant positive latex-specific IgE.

PMID- 29590654
TI  - Identification of Three Novel Frameshift Mutations in the PKD1 Gene in Iranian
      Families with Autosomal Dominant Polycystic Kidney Disease Using Efficient
      Targeted Next-Generation Sequencing.
AB  - BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is one of
      the most common inherited cystic kidney diseases caused by mutations in two large
      multi-exon genes, PKD1 and PKD2. High allelic heterogeneity and duplication of
      PKD1 exons 1-32 as six pseudo genes on chromosome 16 complicate molecular
      analysis of this disease. METHODS: We applied targeted next-generation sequencing
      (NGS) in 9 non-consanguineous unrelated Iranian families with ADPKD to identify
      the genes hosting disease-causing mutations. This approach was confirmed by
      Sanger sequencing. RESULTS: Here, we determined three different novel frameshift
      mutations and four previously reported nonsense mutations in the PKD1 gene
      encoding polycystin1 in heterozygotes. CONCLUSION: This study demonstrates the
      effectiveness of NGS in significantly reducing the cost and time for simultaneous
      sequence analysis of PKD1 and PKD2, simplifying the genetic diagnostics of ADPKD.
      Although a probable correlation between the mutation types and phenotypic outcome
      is possible, however for more extensive studies in future, the consideration of
      renal hypouricemia (RHUC) and PKD1 coexistence may be helpful. The novel
      frameshift mutations reported by this study are p. Q1997X, P. D73X and p. V336X.

PMID- 29590655
TI  - Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF
      kappabeta Pathway in Endotoxin-Induced Uveitis.
AB  - BACKGROUND/AIMS: Lipocalin 2 (LCN2), an important mediator of a variety of
      cellular processes, is involved in regulating the inflammatory response, but its
      roles in different inflammatory diseases are controversial. Because the role of
      LCN2 in ocular inflammation has been unclear until now, we explored the function
      of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in
      vitro. METHODS: Endotoxin-induced uveitis (EIU) was induced in male Sprague
      Dawley rats by the intravitreal injection of LPS. The expression and location of
      LCN2 in the retina were detected with western blotting and immunohistochemistry,
      respectively. We determined the clinical scores for anterior inflammation,
      quantified the infiltrated inflammatory cells, and measured the pro-inflammatory
      factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured
      primary rat Muller cells were stimulated with LPS and the expression and
      secretion of LCN2 were measured with real-time PCR, western blotting, and an
      ELISA. After Muller cells were cotreated with LPS and LCN2 or PBS, the expression
      and secretion of TNF-alpha, IL-6, and MCP-1 were examined with realtime PCR,
      western blotting, and ELISAs. Western blotting and immunofluorescence were used
      to detect the phosphorylation and cellular distribution of nuclear factor kappaB
      (NF-kappaB) subunit p65. RESULTS: In EIU, the expression of LCN2 was
      significantly upregulated in the retina, especially in the outer nuclear layer
      (mainly composed of Muller cells). LPS stimulation of cultured Muller cells also
      markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly
      reduced the clinical scores, inflammatory infiltration, and protein leakage in
      EIU, which correlated with the reduced levels of proinflammatory factors in the
      aqueous humor and retina. LCN2 treatment also reduced the expression and
      secretion of TNF-alpha, IL-6, and MCP-1 in LPS-stimulated Muller cells. LCN2
      inhibited the inflammatory response by inhibiting the phosphorylation and
      translocation of NF-kappaB p65. CONCLUSIONS: LCN2 protects against ocular
      inflammation, at least in part, by negatively regulating the activation of the NF
      kappaB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for
      ocular diseases, such as uveitis.

PMID- 29590656
TI  - Epiretinal Proliferations Associated with Lamellar Macular Holes: Clinical and
      Surgical Implications.
AB  - OBJECTIVES: To describe the prevalence of lamellar hole-associated epiretinal
      proliferation (LHEP) and to correlate this finding with lamellar macular hole
      (LMH) morphology and prognosis after a surgical or conservative approach.
      METHODS: This is a retrospective multicenter case series comprising consecutive
      LMH patients followed for >=6 months. Serial spectral-domain optical coherence
      tomographies were evaluated for the presence of epiretinal membrane (ERM) and
      LHEP, diameter of the LMH aperture, base, and floor thickness. Pars plana
      vitrectomy with ERM and internal limiting membrane peeling was performed in the
      surgical cases. RESULTS: A total of 62 eyes from 57 consecutive patients were
      included. Mean follow-up time was 27.1 +/- 19.8 months. LHEP was observed in 33
      (53.2%) eyes. Patients with LMH and LHEP presented a larger external diameter (p
      = 0.001) and thinner floors (p = 0.018). Twenty-seven (81.8%) of the patients
      with LMH and LHEP presented a degenerative intraretinal cavitation, compared to
      23.3% in the non-LHEP group (p = 0.001). No differences were observed in visual
      performance or closure rate between the 2 groups after surgery or in the subset
      of patients followed conservatively. CONCLUSIONS: LHEP was correlated with the
      anatomical conformation of the LMH, yielding thinner floors and larger external
      diameters. However, it did not correlate with the anatomical or functional
      results, both in the patients who underwent surgery and in those managed
      conservatively.

PMID- 29590657
TI  - Angiotensin II Suppresses Rev-erbalpha Expression in THP-1 Macrophages via the
      Ang II Type 1 Receptor/Liver X Receptor alpha Pathway.
AB  - BACKGROUND/AIMS: Angiotensin II (Ang II) regulates the expression of some core
      clock genes; excess Ang II leads to atherosclerosis advancement. Macrophage Rev
      erbalpha mediates clockwork and inflammation, and plays a role in atherosclerotic
      lesion progression. However, the role of Ang II in regulating Rev-erbalpha
      expression in macrophages remains unclarified. METHODS: We induced THP-1
      macrophages by phorbol 12-myristate 13-acetate and investigated the effect of Ang
      II on Rev-erbalpha expression via real-time polymerase chain reaction, western
      blotting and small interfering RNA (siRNA) techniques. The cytotoxicity of the
      Rev-erbalpha agonist SR9009 was analyzed using a (3-[4,5-dimethylthiazol-2-yl])
      2,5- diphenyltetrazolium bromide assay. RESULTS: Ang II suppressed Rev-erbalpha
      mRNA and protein expression in THP-1 macrophages in a dose and time dependent
      manner. This effect was mediated via Ang II type 1 receptor (AT1R), and not Ang
      II type 2 receptor or peroxisome proliferator-activated receptor gamma
      (PPARgamma). Consistent with Rev-erbalpha expression regulated by Ang II, the
      liver X receptor alpha (LXRalpha) protein expression was downregulated in a time
      dependent manner after Ang II treatment. The activation or silence of LXRalpha
      significantly increased or decreased Rev-erbalpha expression regulated by Ang II,
      respectively. This suggests that LXRalpha is involved in the effect of Ang II on
      Rev-erbalpha expression. MMP-9 mRNA expressions were significantly suppressed by
      SR9009 in THP-1 and RAW264.7 macrophages; moreover, SR9009-treatment
      significantly reduced Ang II-induced MMP-9 protein expressions in two types of
      macrophages. CONCLUSION: Ang II downregulates Rev-erbalpha expression in THP-1
      macrophages via the AT1R/LXRalpha pathway.

PMID- 29590658
TI  - Effects of Fifty-Hertz Electromagnetic Fields on Granulocytic Differentiation of
      ATRA-Treated Acute Promyelocytic Leukemia NB4 Cells.
AB  - BACKGROUND/AIMS: Life on Earth is constantly exposed to electromagnetic fields
      (EMFs) and the effects induced by EMFs on biological systems have been
      extensively studied producing different and sometimes contradictory results.
      Extremely low-frequency electromagnetic fields (ELF-EMFs) have shown to play a
      role in regulating cell proliferation and differentiation, although how EMFs
      influence these processes remains unclear. Human acute promyelocytic leukemia
      (APL) cells are characterized by the arrest of differentiation at the
      promyelocytic stage due to epigenetic perturbations induced by PML/RARalpha
      fusion protein (Promyelocytic Leukemia protein - PML/Retinoic Acid Receptor alpha
      - RARalpha). Therapeutic administration of all-trans retinoic acid (ATRA) re
      establishes the leukemogenic mechanism re-inducing the normal differentiation
      processes. METHODS: We studied the effects of ELF-EMFs (50 Hz, 2 mT) on the ATRA
      mediated granulocytic differentiation process of APL NB4 cells (a cell line
      established from the bone marrow of a patient affected by the acute promyelocytic
      leukemia) by monitoring cellular proliferation and morphology, nitrob lue
      tetrazolium (NBT) reduction and the expression of differentiation surface
      markers. Finally, we investigated mechanisms focusing on reactive oxygen species
      (ROS) generation and related molecular pathways. RESULTS: ELF-EMF exposure
      decreases cellular proliferation potential and helps ATRA-treated NB4 cells to
      mature. Furthermore, the analysis of ROS production and the consequent
      extracellular signal regulated kinases (ERK1/2) phosphorylation suggest that a
      changed intracellular oxidative balance may influence the biological effects of
      ELF-EMFs. CONCLUSIONS: These results indicate that the exposure to ELF-EMF
      promotes ATRA-induced granulocytic differentiation of APL cells.

PMID- 29590659
TI  - LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance
      the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of
      Endothelial Progenitor Cells.
AB  - BACKGROUND/AIMS: In the process of bone development and remodeling, the
      vasculature is regarded as the communicative network between the bone and
      neighboring tissues. Recently, it has been reported that the processes of
      angiogenesis and osteogenesis are coupled temporally and spatially. However, few
      studies reported the relationship and relevant mechanism between
      osteoclastogenesis and vasculogenesis. METHODS: Arraystar Mouse lncRNA microarray
      V3.0 was firstly used to analyze the differentially expressed lncRNA genes in
      osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK
      8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis,
      migration and tube formation assays were used to detect impact of osteoclast
      different stages on the proliferation, differentiation, migration and tube
      formation of endothelial progenitor cells (EPCs), respectively. Finally,
      transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR,
      western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ
      hybridization (FISH) and luciferase reporter assay were carried out to dissect
      molecular mechanisms. RESULTS: In this study, we found that newborn OCs (N-OC)
      and mature OCs (M-OC) during osteoclastogenesis significantly promoted
      proliferation, differentiation, migration and tube formation of endothelial
      progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we
      found that AK131850 and co-expressed gene, vascular endothelial growth factor a
      (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of
      AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore,
      we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through
      sponge, thereby increasing VEGFa transcription, expression and secretion through
      derepressing of miR-93-5p on VEGFa. CONCLUSION: Our results provided the first
      finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during
      osteoclastogenesis to enhance the secretion of VEGFa, thus promoting
      vasculogenesis of EPCs.

PMID- 29590660
TI  - The Role of Y-Box Binding Protein 1 in Kidney Injury: Friend or Foe?
AB  - Y-box-binding protein 1 (YB-1) is a multifunctional protein involved in various
      cellular processes via the transcriptional and translational regulation of target
      gene expression. YB-1 promotes acute or chronic kidney injury through multiple
      molecular pathways; however, accumulating evidence suggests that significantly
      increased YB-1 levels are of great importance in renoprotection. In addition, YB
      1 may contribute to obesity-related kidney disease by promoting adipogenesis.
      Thus, the role of YB-1 in kidney injury is complicated, and no comprehensive
      review is currently available. In this review, we summarise recent progress in
      our understanding of the function of YB-1 in kidney injury and provide an
      overview of the dual role of YB-1 in kidney disease. Moreover, we propose that YB
      1 is a potential therapeutic target to restrict kidney disease.

PMID- 29590661
TI  - Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress
      via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells.
AB  - BACKGROUND/AIMS: Protodioscin (PD) is a steroidal saponin with anti-cancer
      effects on a number of cancer cells, but the anti-tumor effects and mechanism of
      action of PD on human cervical cancer cells is unclear. METHODS: We determined
      cell viability using the MTT assay. Cell death, mitochondrial membrane potential
      (MMP), intracellular reactive oxygen species (ROS) generation, and endoplasmic
      reticulum (ER) stress were measured on a flow cytometry. Caspase activation, ER
      stress, and MMP-dependent apoptosis proteins in cervical cancer cells in response
      to PD were determined by Western blot analysis. The ability of ATF4 binding to
      ChIP promoter was measured using the ChIP assay. RESULTS: We demonstrated that PD
      inhibits cell viability, causes a loss of mitochondrial function, and induces
      apoptosis, as evidenced by up-regulation of caspase-8, -3, -9, -PARP, and Bax
      activation, and down-regulation of Bcl-2 expression. PD was shown to induce ROS
      and the ER stress pathway, including GRP78, p-eIF-2alpha, ATF4, and CHOP. Pre
      treatment with NAC, a ROS production inhibitor, significantly reduced ER stress
      and apoptosis-related proteins induced by PD. Transfection of GRP78/CHOP-siRNA
      effectively inhibited PD-induced ER stress-dependent apoptosis. Moreover,
      treatment with PD significantly increased p38 and JNK activation. Co
      administration of a JNK inhibitor (SP600125) or p38 inhibitor (SB203580)
      abolished cell death and ER stress effects during PD treatment. In addition, PD
      induced the expression of nuclear ATF4 and CHOP, as well as the binding ability
      of ATF4 to the CHOP promoter. CONCLUSION: Our results suggest that PD is a
      promising therapeutic agent for the treatment of human cervical cancer.

PMID- 29590662
TI  - Urinary Iron Excretion is Associated with Urinary Full-Length Megalin and Renal
      Oxidative Stress in Chronic Kidney Disease.
AB  - BACKGROUND/AIMS: Megalin mediates the uptake of glomerular-filtered iron in the
      proximal tubules. Urinary full length megalin (C-megalin) excretion has been
      found to be increased in association with megalin-mediated metabolic load to the
      endo-lysosomal system in proximal tubular epithelial cells (PTECs) of residual
      nephrons. In the present study, we investigated the association between urinary
      iron and C-megalin in chronic kidney disease (CKD) patients, and the possible
      harmful effect of iron in renal tubules. METHODS: Urinary levels of iron and C
      megalin were measured in 63 CKD patients using automatic absorption spectrometry
      and a recently-established sandwich ELISA, respectively. RESULTS: Although both
      urinary C-megalin and urinary total protein levels were correlated with urinary
      iron (C-megalin: rho = 0.574, p <0.001; total protein: rho = 0.500, p <0.001,
      respectively), urinary C-megalin alone emerged as an independent factor
      positively associated with urinary iron (beta = 0.520, p <0.001) (R2 = 0.75, p
      <0.001). Furthermore, urinary iron was significantly and positively associated
      with urinary 8-hydroxydeoxyguanosine, an oxidative stress marker, while no
      association with other markers of renal tubular injury, i.e., beta2-microglobulin
      and N-acetyl-beta-D-glucosaminidase, was noted. CONCLUSIONS: Our findings suggest
      that renal iron handling may be associated with megalin-mediated endo-lysosomal
      metabolic load in PTECs of residual nephrons and oxidative stress in renal
      tubules.

PMID- 29590663
TI  - Do Ultra-Low Multidetector Computed Tomography Doses and Iterative Reconstruction
      Techniques Affect Subjective Classification of Bone Type at Dental Implant Sites?
AB  - PURPOSE: To investigate whether ultra-low-dose multidetector computed tomography
      (MDCT) combined with the reconstruction techniques filtered backprojection (FBP),
      adaptive statistical iterative reconstruction (ASIR), or model-based iterative
      reconstruction (MBIR) alters the subjective classification of revised Lekholm and
      Zarb (LZ) bone types at prospective dental implant sites. MATERIALS AND METHODS:
      Three cadavers underwent a reference MDCT examination using a standard dose
      volume (CT dose index [CTDIvol]: 29.4 mGy) and reconstructed with FBP in addition
      to five test protocols (LD1-LD5) using ultra-low doses (CTDIvol: 4.19, 2.64,
      0.99, 0.53, and 0.29 mGy, respectively) and reconstructed with FBP, ASIR 50, ASIR
      100, and MBIR. Transverse cross-sectional images of the jawbones were obtained,
      and three examiners subjectively classified the bone type in each image using the
      revised LZ classification. The bone type classifications obtained using the
      reference examination were compared with those obtained from the test protocols
      for each examiner, and kappa statistic was used to analyze the level of agreement
      between the reference and test protocols. The clinical significance of the
      differences was analyzed with Wilcoxon signed rank test. RESULTS: Examiners 1 and
      2 found moderate to strong agreement between the reference and test protocols,
      while Examiner 3 found strong to almost perfect agreement (P < .001). The
      Wilcoxon signed rank test did not demonstrate a clinical significance of the
      differences between the reference and test protocols for any of the three
      examiners. CONCLUSION: MDCT dose reductions of up to 99% did not significantly
      alter the subjective classification of bone at dental implant sites.

PMID- 29590664
TI  - The Role of Portable Documentation Format in Three-Dimensional Interactive
      Visualization in Maxillofacial Prosthetics.
AB  - Although digital technology has advanced the visualization of treatment planning
      and rehabilitation in prosthodontics, the field of maxillofacial prosthetics is
      in vital need of an accessible document for exchange of interactive three
      dimensional (3D) model visualization without requiring installation of any
      additional software. This article introduces a 3D data documentation method for
      effective interactive digital visualization in maxillofacial prosthetics using a
      portable documentation format (PDF).

PMID- 29590666
TI  - Effect of Premolar Axial Wall Height on Computer-Aided Design/Computer-Assisted
      Manufacture Crown Retention.
AB  - PURPOSE: To evaluate the effect of premolar axial wall height on the retention of
      adhesive, full-coverage, computer-aided design/computer-assisted manufacture
      (CAD/CAM) restorations. MATERIALS AND METHODS: A total of 48 premolar teeth
      randomized into four groups (n = 12 per group) received all-ceramic CAD/CAM
      restorations with axial wall heights (AWH) of 3, 2, 1, and 0 mm and 16-degree
      total occlusal convergence (TOC). Specimens were restored with lithium disilicate
      material and cemented with self-adhesive resin cement. Specimens were loaded to
      failure after 24 hours. RESULTS: The 3- and 2-mm AWH specimens demonstrated
      significantly greater failure load. Failure analysis suggests a 2-mm minimum AWH
      for premolars with a TOC of 16 degrees. CONCLUSION: Adhesive technology may
      compensate for compromised AWH.

PMID- 29590667
TI  - ?

PMID- 29590668
TI  - Safety of lumen-apposing stent with or without coaxial plastic stent for
      endoscopic ultrasound-guided drainage of pancreatic fluid collections: a
      retrospective study.
AB  - BACKGROUND:  The aim of this study was to evaluate whether the placement of a
      coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent
      (LAMS) may improve the safety of endoscopic ultrasound (EUS)-guided drainage of
      pancreatic fluid collections (PFCs). METHODS:  This was a retrospective cohort
      study including patients with PFCs and an indication for transmural drainage. Two
      strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist's
      discretion. RESULTS:  A total of 41 patients were treated (21 LAMS alone; 20 LAMS
      plus DPS). The characteristics of the PFCs, and the technical and clinical
      success rates did not differ between groups. The LAMS alone group had a
      significantly higher rate of adverse events than the LAMS plus DPS group (42.9 %
      vs. 10.0 %; P = 0.04). Bleeding was the most frequent adverse event observed.
      CONCLUSIONS:  The addition of a coaxial DPS to LAMS was associated with a lower
      rate of adverse events in EUS-guided drainage of PFCs.

PMID- 29590669
TI  - Colonoscopic perforations in the English National Health Service Bowel Cancer
      Screening Programme.
AB  - BACKGROUND: Perforation is the most serious adverse event associated with
      colonoscopy. In this study of data from the English National Health Service Bowel
      Cancer Screening Programme, we aimed to describe the presentation and management
      of perforations, and to determine factors associated with poorer outcomes post
      perforation. METHODS: The medical records of patients with a perforation
      following the national screening colonoscopy were retrospectively examined. All
      colonoscopies performed from 02/08/2006 to 13/03/2014 were studied. Bowel Cancer
      Screening Centres across England were contacted and asked to complete a detailed
      dataset relating to perforation presentation, management, and outcome. RESULTS:
      263 129 colonoscopies were analyzed, and the rate of perforation was 0.06 %.
      Complete data were reviewed for 117 perforations: 70.1 % of perforations (82/117)
      occurred during therapeutic colonoscopies; 54.9 % (62/113) of patients with
      perforations who were admitted to hospital and in whom data were complete
      underwent surgery; 26.1 % (30/115) of hospitalized patients left the hospital
      with a stoma and 19.1 % (22/115) developed post-perforation morbidity.
      Perforations not detected during colonoscopy were significantly more likely to
      require surgery (P = 0.03). Diagnostic perforations were significantly more
      likely to require surgery (P = 0.002) and were associated with higher rates of
      post-perforation morbidity (P = 0.01). At presentation, the presence of abdominal
      pain (P = 0.01), a pulse rate > 100 beats per minute (P = 0.049), and a
      respiratory rate > 20 breaths per minute (P = 0.01) were significantly associated
      with the patient having surgery. CONCLUSIONS: This is the largest retrospective
      observational case series in Europe to describe post-perforation presentation,
      management, and outcomes. We have confirmed that perforation leads to surgical
      intervention, stoma formation, and post-perforation morbidity. Perforations not
      recognized during the colonoscopy were significantly more likely to require
      surgery. Diagnostic perforations were at greater risk of requiring surgery and
      developing post-perforation morbidity.

PMID- 29590670
TI  - CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and
      Bleeding Events following Transcatheter Aortic Valve Replacement.
AB  - BACKGROUND:  Paravalvular aortic regurgitation (PVAR) remains a frequent
      postprocedural concern following transcatheter aortic valve replacement (TAVR).
      Persistence of flow turbulence results in the cleavage of high-molecular-weight
      von Willebrand multimers, primary haemostasis dysfunction and may favour
      bleedings. Recent data have emphasized the value of a point-of-care measure of
      von Willebrand factor-dependent platelet function (closure time [CT] adenosine
      diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined
      whether CT-ADP could detect PVAR at 30 days and bleeding complications following
      TAVR. METHODS:  CT-ADP was assessed at baseline and the day after the procedure.
      At 30 days, significant PVAR was defined as a circumferential extent of
      regurgitation more than 10% by transthoracic echocardiography. Events at follow
      up were assessed according to the Valve Academic Research Consortium-2 consensus
      classification. RESULTS:  Significant PVAR was diagnosed in 44 out of 219
      patients (20.1%). Important reduction of CT-ADP could be found in patients
      without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR
      patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1,
      95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve
      were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural
      CT-ADP >180 seconds was identified as an independent predictor of major/life
      threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life
      threatening bleedings were at their highest levels in patients with
      postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION: 
      Postprocedural CT-ADP > 180 seconds is an independent predictor of significant
      PVAR 30 days after TAVR and may independently contribute to major/life
      threatening bleedings.

PMID- 29590671
TI  - Primary Graft Dysfunction (PGD) Following Lung Transplantation.
AB  - Primary graft dysfunction (PGD) is a form of acute lung injury that results from
      ischemia reperfusion injury (IRI) and is the major cause of early posttransplant
      morbidity and mortality. Patients who survive PGD have decreased quality of life,
      an increased risk of chronic lung allograft dysfunction, specifically
      bronchiolitis obliterans syndrome, and a significantly increased risk of death.
      In 2017, the International Society for Heart and Lung Transplantation released
      updated consensus statements on the PGD definition, most up-to-date PGD risk
      factors, mechanisms of PGD development, and the state-of-the-art for PGD
      therapeutics. Risk factor identification has led to the development of PGD
      predictive algorithms, although their clinical utility remains limited. Ongoing
      areas of controversy and discussion include further refinements to the PGD
      grading scheme to account for technologic advances such as extracorporeal
      membrane oxygenation and the increased utilization of high flow nasal cannula,
      the use of PGD as an outcome measure in clinical trials of ex vivo lung
      perfusion, enhancement of predictive algorithms incorporating biochemical risk
      factors, and the need for development of therapies targeted at improving PGD
      outcomes.

PMID- 29590672
TI  - Prenatally Diagnosed Single Umbilical Artery (SUA) - Retrospective Analysis of
      1169 Fetuses.
AB  - PURPOSE:  The incidence of a fetal single umbilical artery (SUA) is about 0.5 %
      and has been associated with an increased risk of congenital malformations, fetal
      aneuploidy and intrauterine growth restriction (IUGR). MATERIALS AND METHODS:  A
      retrospective analysis of 1169 women with singleton pregnancies diagnosed with
      fetal SUA between 1997 and 2014 in a specialized practice for prenatal
      diagnostics has been performed. Data was obtained on maternal and fetal findings
      as well as pregnancy outcome. RESULTS:  989 (84.6 %) fetuses showed an isolated
      SUA (iSUA) while 180 (15.4 %) presented with SUA and additional structural and/or
      chromosomal abnormalities. Structural malformations were distributed as follows:
      9.0 % cardiovascular, 3.5 % urogenital, 2.9 % musculoskeletal, 3.0 %
      gastrointestinal and 2.1 % cerebral. 2.1 % of the fetuses had chromosomal
      aberrations. 50.8 % (49.2 %) of the fetuses were female (male) and right vs. left
      SUA was found in 64.2 % (35.8 %) of the cases. Fetuses with SUA and additional
      abnormalities showed lower rates of live births (85.0 % vs. 98.5 %, p < 0.001), a
      lower median birth weight (2825 g vs. 3220 g, p < 0.001), higher rates of preterm
      delivery before week 34 + 0 (13.7 % vs. 3.8 %, p < 0.001) and weighed less than
      the 5th growth percentile in 21.6 % vs. 9.3 % (p < 0.001) of the fetuses with
      iSUA. In 5.1 % (60) of the children, chromosomal or structural abnormalities were
      detected post-partum. CONCLUSION:  Once fetal SUA is diagnosed, intense
      sonoanatomy of the fetus is required and, if associated malformations are found,
      genetic testing must be offered. In iSUA intermittent biometry is recommended for
      the early detection of IUGR but additional genetic testing is not necessarily
      recommended.

PMID- 29590673
TI  - ?

PMID- 29590674
TI  - [Influence of glucocorticoid therapy on intratherapeutic biodistribution of 131I
      radioiodine therapy in Graves' disease].
AB  - AIM: Radioiodine therapy (RIT) is an important therapeutic method in the
      definitive treatment of Graves' disease (GD). However, RIT may trigger
      development of Graves' ophthalmopathy (GO) or exacerbate a pre-existing GO.
      Therefore, the procedure recommendation of the DGN (German Society of Nuclear
      Medicine) for RIT of benign thyroid diseases recommends an additional
      glucocorticoid therapy for patients with pre-existing GO. Aim of this study was
      to analyze the influence of a protective glucocorticoid therapy on 131I
      biokinetics during RIT of patients with GD. MATERIAL AND METHODS: In this
      retrospective analysis 211 patients with GD who underwent RIT without additional
      thyreostatic medication were examined. To analyze 131I biokinetics the
      extrapolated maximum uptake (EMU) and the effective half-life of 131I in the
      thyroid were determined. Patients suffering from GO received glucocorticoids
      according to a fixed scheme starting one day prior to RIT, patients without GO
      did not receive glucocorticoids. Subsequently the ratios of values measured
      during RIT and those measured during radioactive iodine uptake test were compared
      among the groups. To take into account other factors, the groups were also
      compared regarding age, weight, TSH, TRAb, TgAb and TPOAb. RESULTS: In patients
      with additional glucocorticoid therapy, a reduction of the median EMU from 44 %
      in radioiodine uptake test to 35 % during RIT was observed. The pretherapeutic
      (47 %) and intratherapeutic (46 %) EMU of the control group without
      glucocorticoids remained constant. Comparison of the change in the EMU showed a
      statistically significant difference between both groups (p < 0.001). Comparison
      of all other parameters including the effective half-life of 131I (p = 0.79) did
      not show any statistically significant difference. CONCLUSION: The present study
      suggests that glucocorticoids affect the biokinetics of 131I by reducing its
      thyroidal uptake. As a result of this study, for patients without antithyroid
      medication undergoing glucocorticoid therapy, an adjustment of therapeutic 131I
      activity determined in radioiodine uptake test could be considered.

PMID- 29590675
TI  - Influence of scan time point and volume of intravenous contrast administration on
      blood-pool and liver SUVmax and SUVmean in [18F] FDG PET/CT.
AB  - AIM: To investigate the influence of scan time point and volume of intravenous
      contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake
      values (SUVmax/mean) in bloodpool and liver. METHODS: In 120 patients scheduled
      for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake
      values (SUVmax/SUVmean) in the liver and blood pool were measured after varying
      scan time-point (delay 0 s-140 s post injectionem) and volume of contrast
      material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine). Six groups of 20
      patients were investigated: (1) without intravenous CM, (2-5) injection of 100 ml
      CM with a delay of 80 s (2), 100 s (3), 120 s (4), 140 s (5), and 80 ml CM and a
      delay of 100 s (6). SUVmax, SUVmean, maximum Hounsfield units (HUmax) and average
      Hounsfield units (HUav) were calculated with the use of manually drawn regions of
      interests (ROIs) over the aortic arch and healthy liver tissue. RESULTS: SUVmax
      in bloodpool was significantly higher in group 3, 4 and 6 compared to group 1.
      Groups 2 and 5 also showed higher mean values of SUVmax, but the difference was
      not significant. SUVmean in bloodpool was also higher in groups 2, 3, 4, 5 and 6
      compared to group 1, but the differences were only statistically significant in
      group 3. Both SUVmax and SUVmean in healthy liver tissue did not show significant
      differences when compared to the non contrast-enhanced control group. CONCLUSION:
      SUVmax and to a lesser extent SUVmean measured in CM enhanced FDG PET/CT in blood
      pool could be significantly altered in high contrast CT examinations. This should
      be kept in mind in PET/CT protocols and evaluation relying on SUVmax and SUVmean,
      for example when used in the assessment of therapy response, especially in highly
      vascularized tumor lesions. ZIEL:: Das Ziel dieser Studie war den Einfluss von
      unterschiedlichen Messzeitpunkten und Volumina bei der Gabe von intravenosem
      Kontrastmittel in der 18F-FDG PET/CT auf SUVmax und SUVmean im Blutpool und
      Lebergewebe zu untersuchen. METHODEN: In 120 Patienten, geplant fur eine
      Ganzkorper 18F-FDG -PET/CT, wurden die maximalen und durchschnittlichen
      standardisierten Aufnahmewerte (SUVmax/SUVmean) in der Leber und im Blutpool,
      jeweils nach unterschiedlichen Messzeitpunkten (Verzogerung 0 s-140 s post
      injectionem) und verschiedenen Volumina von Kontrastmittel (KM; 0 ml, 80 ml, 100
      ml mit einer Konzentration von 300 mg/ml Jod) gemessen. Sechs Gruppen von je 20
      Patienten wurden untersucht: (1) ohne intravenoses KM, (2-5) Injektion von 100 ml
      KM mit einer Verzogerung von 80 s (2), 100 s (3), 120 s (4), 140 s (5), und 80 ml
      KM mit einer Verzogerung von 100 s (6). Es wurden jeweils die SUVmax, SUVmean,
      die maximalen and die durchschnittlichen Hounsfield Einheiten (HUav, HUmax)
      anhand manuell gezeichneter Bereiche von Interesse (ROIs) im Aortenbogen und im
      gesunden Lebergewebe berechnet. ERGEBNISSE: Die SUVmax im Blutpool waren im
      Vergleich zur Gruppe 1 signifikant hoher in Gruppe 3, 4 und 6. Die Gruppen 2 und
      5 zeigten ebenfalls hohere Durchschnittswerte von SUVmax, der Unterschied war
      jedoch nicht signifikant. Die SUVmean im Blutpool waren im Vergleich zur Gruppe 1
      ebenfalls hoher in den Gruppen 2, 3, 4, 5 und 6, allerdings waren die
      Unterschiede nur in Gruppe 3 statistisch signifikant. Im Lebergewebe zeigten
      sowohl SUVmax, als auch SUVmean keine signifikanten Unterschiede im Vergleich zu
      der nativen Kontrollgruppe. SCHLUSSFOLGERUNGEN: In der Kontrastmittel-gestutzten
      FDG PET/CT konnen die SUVmax und in geringerem Ausmabeta auch SUVmean im Blutpool
      durch Hochkontrast-CT Untersuchungen signifikant beeinflusst werden. Dies sollte
      bei PET/CT Protokollen bzw. Auswertungen, die auf SUVmax und SUVmean beruhen,
      berucksichtigt werden, zum Beispiel bei der Beurteilung des Therapieansprechens
      insbesondere bei stark vaskularisiertem Tumorgewebe.

PMID- 29590676
TI  - Radiotoxicity of alpha particles versus high and low energy electrons in hypoxic
      cancer cells.
AB  - PURPOSE: Hypoxic regions of tumors are less sensitive to radio- and chemotherapy,
      leading to poor prognosis of patients. One option to overcome the radioresistance
      is the irradiation of hypoxic tumors with high linear energy transfer (LET) alpha
      or Auger electronemitters assuming their radiotoxicity would be less dependent
      on the cellular oxygenation status. Therefore, the aim of the present study was
      to determine whether irradiation with the intracellularly distributed Auger
      electron/gamma-emitter 99mTc using the tracer [99mTc]TcHMPAO is a promising
      therapeutic option for the treatment of hypoxic tumor cells. Thus, the high LET
      alpha-particleemitter 223Ra ([223Ra]RaCl2) and the low LET beta-emitter 188Re
      ([188Re]NaReO4) were studied in comparison to [99mTc]Tc-HMPAO. MATERIALS AND
      METHODS: A431 tumor cells were incubated with [99mTc]Tc-HMPAO (1-20 MBq/2 mL),
      [223Ra]RaCl2 (1.4-16.3 kBq/2 mL) or [188Re]NaReO4 (0.3-13.7 MBq/2 mL) under
      normoxic or hypoxic conditions. The degree of radiotoxicity was analyzed using
      the colony forming assay (CFA), and the intracellular radionuclide uptake of the
      radiotracers was quantified. RESULTS: Hypoxic A431 cells are less radiosensitive
      to irradiation with [99mTc]Tc-HMPAO or [188Re]NaReO4 than normoxic ones. In
      contrast, the radiosensitivity of A431 cells is almost independent of the oxygen
      status when treated with the [223Ra]RaCl2. CONCLUSIONS: We demonstrate that the
      Auger electron/gamma-emitter 99mTc ([99mTc]Tc-HMPAO), which does not bound
      directly to the DNA, is not a promising therapeutic option for hypoxic tumor
      cells. But the high LET alpha-particle-emitter 223Ra is more suitable for the
      treatment of hypoxic tumor cells than irradiation with [99mTc]Tc-HMPAO or the low
      LET bemitter 188Re. ZIELSETZUNG: Hypoxische Tumorregionen sind bei Radio- und
      Chemotherapie weniger sensitiv als Tumorregionen mit ausreichender
      Sauerstoffversorgung. Dies verursacht eine schlechte Prognose fur Tumorpatienten.
      Eine Option die Radioresistenz zu uberwinden, stellt die Bestrahlung mit alpha
      Partikel-Emittern oder Auger-Elektronen-Emittern mit einem hohen linearen
      Energietransfer (LET) dar. In dieser Studie soll untersucht werden, ob die
      Bestrahlung von hypoxischen Tumorzellen mit dem intrazellular aufgenommenen gamma
      sowie Auger-Elektronen-Emitter 99mTc unter Verwendung des Radiotracers [99mTc]Tc
      HMPAO eine vielversprechende Therapieoption darstellen konnte. Vergleichend wurde
      der Hoch-LET alpha-Partikel-Emitter 223Ra ([223Ra]RaCl2) und der Niedrig-LET beta
      Emitter 188Re ([188Re]NaReO4) eingesetzt. METHODEN: A431 Tumorzellen wurden unter
      normoxischen oder hypoxischen Kulturbedingungen mit [99mTc]Tc-HMPAO (1-20 MBq/2
      ml), [223Ra]RaCl2 (1,4-16,3 kBq/2 ml) und [188Re]NaReO4 (0,3-13,7 MBq/2 ml)
      inkubiert. Zur Detektion der resultierenden strahlenbiologischen Wirkung wurde
      der Koloniebildungsassay angewendet. Zusatzlich wurde die intrazellulare Aufnahme
      der Radiotracer quantifiziert. ERGEBNISSE: Nach Inkubation von [99mTc]Tc-HMPAO
      sind hypoxische A431-Zellen weniger strahlensensitiv als normoxische Zellen. Im
      Gegensatz zur Behandlung mit [99mTc]Tc-HMPAO oder [188Re]NaReO4 wurde bei
      Behandlung mit [223Ra]RaCl2 ein geringerer Einfluss des Sauerstoffstatus auf die
      Radiosensitivitat von A431-Zellen gefunden. SCHLUSSFOLGERUNG: Damit konnte
      gezeigt werden, dass der nicht direkt an die DNA gebundene Auger-Elektronen-/
      gamma-Emitter 99mTc ([99mTc]Tc-HMPAO) die Radioresistenz von hypoxischen
      Tumorzellen nicht uberwinden kann. Jedoch stellt der Hoch-LET alpha-Partikel
      Emitter 223Ra ([223Ra]RaCl2) eine bessere Behandlungsoption dar.

PMID- 29590677
TI  - Successful handling of an accidental extravasation of 177Lu-PSMA-617 in the
      treatment of advanced prostate cancer.

PMID- 29590678
TI  - ?

PMID- 29590679
TI  - ?

PMID- 29590681
TI  - Text Mining and Automation for Processing of Patient Referrals.
AB  - BACKGROUND:  Various tasks within health care processes are repetitive and time
      consuming, requiring personnel who could be better utilized elsewhere. The task
      of assigning clinical urgency categories to internal patient referrals is one
      such case of a time-consuming process, which may be amenable to automation
      through the application of text mining and natural language processing (NLP)
      techniques. OBJECTIVE:  This article aims to trial and evaluate a pilot study for
      the first component of the task-determining reasons for referrals. METHODS:  Text
      is extracted from scanned patient referrals before being processed to remove
      nonsensical symbols and identify key information. The processed data are compared
      against a list of conditions that represent possible reasons for referral.
      Similarity scores are used as a measure of overlap in terms used in the processed
      data and the condition list. RESULTS:  This pilot study was successful, and
      results indicate that it would be valuable for future research to develop a more
      sophisticated classification model for determining reasons for referrals. Issues
      encountered in the pilot study and methods of addressing them were outlined and
      should be of use to researchers working on similar problems. CONCLUSION:  This
      pilot study successfully demonstrated that there is potential for automating the
      assignment of reasons for referrals and provides a foundation for further work to
      build on. This study also outlined a potential application of text mining and NLP
      to automating a manual task in hospitals to save time of human resources.

PMID- 29590680
TI  - Nutrigenomic Information in the openEHR Data Set.
AB  - BACKGROUND:  The traditional concept of personalized nutrition is based on
      adapting diets according to individual needs and preferences. Discussions about
      personalized nutrition have been on since the Human Genome Project, which has
      sequenced the human genome. Thenceforth, topics such as nutrigenomics have been
      assessed to help in better understanding the genetic variation influence on the
      dietary response and association between nutrients and gene expression. Hence,
      some challenges impaired the understanding about the nowadays important clinical
      data and about clinical data assumed to be important in the future. OBJECTIVE: 
      Finding the main clinical statements in the personalized nutrition field
      (nutrigenomics) to create the future-proof health information system to the
      openEHR server based on archetypes, as well as a specific nutrigenomic template.
      METHODS:  A systematic literature search was conducted in electronic databases
      such as PubMed. The aim of this systemic review was to list the chief clinical
      statements and create archetype and templates for openEHR modeling tools, namely,
      Ocean Archetype Editor and Ocean Template Design. RESULTS:  The literature search
      led to 51 articles; however, just 26 articles were analyzed after all the herein
      adopted inclusion criteria were assessed. Of these total, 117 clinical statements
      were identified, as well as 27 archetype-friendly concepts. Our group modeled
      four new archetypes (waist-to-height ratio, genetic test results, genetic
      summary, and diet plan) and finally created the specific nutrigenomic template
      for nutrition care. CONCLUSION:  The archetypes and the specific openEHR template
      developed in this study gave dieticians and other health professionals an
      important tool to their nutrigenomic clinical practices, besides a set of
      nutrigenomic data to clinical research.

PMID- 29590682
TI  - Peripheral Oxytocin Predicts Higher-Level Social Cognition in Men Regardless of
      Empathy Quotient.
AB  - INTRODUCTION: Pharmaceutical oxytocin (OT) administration is being tested as a
      novel treatment for social deficits in various psychiatric populations. However,
      little is known about how naturally occurring variation in peripheral OT relates
      to differences in social cognition. This study investigates whether healthy
      individuals with very high or very low levels of empathy differ in endogenous OT
      and whether OT plasma levels can predict performance in a mentalizing task.
      METHODS: 40 healthy men were included based upon their score above the 85th or
      below the 15th percentile of the empathy quotient inventory 1. Participants'
      abilities to interpret social information was assessed via the Social Detection
      Task 2. Plasma OT levels were analyzed using enzyme immunoassay. RESULTS: OT
      plasma levels predicted mentalizing performance for more ambiguous social scenes
      (i. e., difficult items) for all participants. We found no group differences in
      OT plasma levels between subjects with high and low empathy. DISCUSSION: These
      findings confirm a link between peripheral OT and the ability to read subtle
      nonverbal social cues in healthy individuals, which is independent of self
      reported empathy.

PMID- 29590683
TI  - Spontaneous Regression of Iris Melanocytoma: A Case Report.

PMID- 29590684
TI  - [Morphological and Quantitative Changes in Retinal and Optic Nerve Vessels in
      Experimental Glaucoma Model with Elevated IOP for 7 Weeks].
AB  - INTRODUCTION: Glaucoma is characterised by progressive loss of retinal ganglion
      cells and axons. Experimental research has concentrated on understanding the
      pathophysiological mechanisms involved in glaucomatous damage. It is still a
      matter of debate whether neurons or capillaries are primarily damaged by elevated
      intraocular pressure (IOP). The aim of this study was to detect IOP-induced
      vascular changes in the vessels of the optic nerve head and the main vessels of
      the retina in vivo. METHODS: Experimental glaucoma was induced in adult Sprague
      Dawley rats by cauterisation of three episcleral veins of the left eye (n = 3).
      In vivo, retinal vessel calibre was measured manually using a peripapillary scan
      with SD-OCT (Heidelberg Engineering) at baseline and after seven weeks of IOP
      elevation. The animals were then sacrificed and the optic nerve was fixed with
      30% glutaraldehyde and cross-sections stained with paraphenylene diamine to mark
      the vessels. Contralateral eyes served as controls. Pictures were taken and
      number of vessels, vessel calibre and area were calculated and compared. RESULTS:
      IOP was significantly elevated (p < 0.001). In optic nerve cross sections, the
      number of capillaries did not differ significantly between animals with elevated
      IOP and controls. However, vessel calibre and area were significantly reduced (p
      < 0.001) in glaucomatous optic nerves. The calibre of the retinal vessels was
      significantly lowered - by 9.22% (p = 0.021). CONCLUSION: Retinal arterioles and
      optic nerve capillaries respond sensitively to abnormal pressure elevation in
      vivo, showing high and early vulnerability. The vascular responses may influence
      secondary neuronal responses, which culminate in the death of ganglion cells and
      blindness, as occurs in clinical glaucoma.

PMID- 29590685
TI  - Skin Ulceration of Eyelids in Atopic Dermatitis.
AB  - BACKGROUND: Superinfection of atopic dermatitis due to a disturbed skin barrier
      is well known. Still, affected eyelids with ulceration are rarely described. We
      present a case series of three patients in different stages of upper eyelid
      superinfection. HISTORY AND SIGNS: Three males aged 58, 37, and 52 years with
      clinical symptomatology of gradual expansion of eyelid ulcerations, crusts, and
      pus were evaluated. In all cases a standard ophthalmologic examination, including
      a detailed neuro-ophthalmological status, was performed. Consequently, a skin
      swab was obtained. THERAPY AND OUTCOME: The completed neuro-ophthalmological
      status and posterior segment findings were unremarkable in all patients. The skin
      swab results confirmed the presence of Streptococcus pyogenes, Staphylococcus
      epidermidis, and Staphylococcus aureus, thus necessitating antibiotic therapy.
      CONCLUSIONS: Superinfected atopic dermatitis can develop massive ulcerations,
      indicating a swap and empiric therapy. A complete neuro-ophthalmological status
      is mandatory to exclude the possibility of orbital involvement. Nevertheless, any
      paradoxical worsening of symptomatology indicates further referral to a
      dermatologist.

PMID- 29590686
TI  - [Long-Term Results after Trabeculectomy Combined with Mitomycin C and Ologen
      Implant].
AB  - BACKGROUND: The Ologen implant consists of a biodegradable collagen and
      glycosaminoglycan and is intended to avoid postoperative bleb scarring or
      encapsulation. MATERIALS AND METHODS: In a retrospective clinical study, 806
      patients with advanced glaucoma were treated with trabeculectomy combined with
      mitomycin C0.02% and Ologen implant. The follow-up time of the study was 8 years.
      RESULTS: A long-term reduction of the intraocular pressure below 16 mmHg was
      achieved in 92.6% of the patients without glaucoma eye drops in the long-term
      observation period. The rate of complication was very low during the
      postoperative period and additional surgical procedures for over-filtration with
      subsequent choroidal detachment were seen in 6.8% of the patients. A failure of
      the combined operation with phacoemulsification and implantation of an
      intraocular lens resulted in revision of the bleb or the application of
      compressive sutures in 3.35% of patients within 8 years. CONCLUSION: The Ologen
      implant was introduced in glaucoma surgery to increase the effectiveness of
      trabeculectomy and to reduce the complications. Trabeculectomy combined with
      mitomycin C0.02% and an Ologen implant provides a satisfactory filtering effect
      without the undesirable effects of postoperative fibrosis.

PMID- 29590687
TI  - Comparative Study of the Usefulness of the Binocular Spot Vision Screener
      Autorefractor in the Detection of Childhood Visual Disorders.
AB  - BACKGROUND: The Spot Vision Screener (SVS) is designed to detect significant
      ametropia, anisometropia, and strabismus in non-dilated eyes. This study
      evaluates the efficacy of the SVS in paediatric visual screening. PATIENTS AND
      METHODS: All children screened during the paediatric visual screening day in
      Lausanne in 2016 were evaluated with the SVS, conventional monocular
      autorefractors, and clinical orthoptic examination. Recommendations for a further
      eye examination of the SVS were compared with those issued from traditional
      clinical screenings (monocular refraction and orthoptic examination). RESULTS:
      One hundred and sixty-eight consecutive children were included. The median age
      was 3.9 years. The SVS median spherical equivalent (SE) was + 0.25 D OU and it
      detected seven cases of (4.2%) anisometropia (SE difference >= 1 D). The
      conventional monocular autorefractor median SE was - 0.13 D OU and 20 cases of
      anisometropia (11.9%) were detected. Refraction could not be measured in 1.2% of
      patients with SVS versus 17.2% with monocular refractors. The SVS screened two
      manifest strabismus cases against five manifest and > 100 latent strabismus with
      orthoptic examination. As expected, the SVS was unable to assess reactions to
      monocular occlusion, visual acuity, and stereovision as well as to detect ocular
      motility disorders without strabismus in the primary position, and missed two
      cases of abnormal Bruckner reflexes. Overall, the SVS identified 66 suspect
      patients (39.3%) against 102 (60.7%) after complete clinical examination.
      CONCLUSIONS: The SVS can be a useful objective screening tool for non
      ophthalmologists. However, because it fails to detect ocular motility troubles,
      organic visual acuity loss, or to assess the visual potential, it should only be
      used in association with a clinical examination, even in routine screening
      procedures.

PMID- 29590688
TI  - [Astigmatic Vision - More Than One Hundred Years of Misconceptions, Fallacies and
      Distractions].

PMID- 29590689
TI  - [5th International Conference on Behavioral Addictions in Cologne -A Unique
      Opportunity to Share Scientific Knowledge on Non-Substance Related Addictions].

PMID- 29590691
TI  - ?

PMID- 29590690
TI  - ?

PMID- 29590692
TI  - [Return to Work from Vocational RetrainingA Long-Term Analysis of Individual
      Trajectories: Biografical and Structural Conditions of Success and Failure].
AB  - BACKGROUND AND AIMS: The study aimed at the reconstruction of the trajectories of
      participants of a two-year vocational-retraining into new workplaces thereby
      identifying favourable and risky conditions of the return-to-work process. From a
      practical point of view the study identified special needs and necessities for
      after-care facilities. METHODS: A Mixed-Method-Design was used. Quantitatively
      the follow-up-study included 214 persons who participated for three times on
      filling out a questionnaire over a period of eighteen months after the end of the
      vocational retraining. In the qualitative part of the study thirty persons
      consented to participate in a narrative-episodic interview on their vocational
      biography, their illness experiences at work and their way back into work. The
      study focused on the experiences of the participants from within, on their
      decision-making, coping, and rearrangement processes as well as on the
      experienced support from family members and rehabilitation professionals.
      RESULTS: About 75% of the participants of the vocational retraining succeeded in
      getting a job within the range of 18 months after finishing the retraining.
      Indicators for successful Return to Work are a high identification with the new
      vocation, effective coping with the remaining health problems, and an accepted
      arrangement with the disabilities in the work place and in everyday-life, a
      positive anticipation of the health condition in the future, and last but not
      least a satisfying social inclusion. As specific risk constellations for Return
      to Work emerged a lack of partnership, unfinished mental coping with the illness,
      negative subjective health prognosis, and a more passive attitude to life.

PMID- 29590693
TI  - [Quality Performance Measures in Cardiac Rehabilitation - Results of a Delphi
      Survey of Members of the German Society for Prevention and Rehabilitation of
      Cardiovascular Diseases (DGPR)].
AB  - OBJECTIVE: The present investigation aimed an explorative acquisition of
      potential performance measures for quantifying the quality of cardiac
      rehabilitation (CR) for patients under 65 years of age. METHODS: A 4-level web
      based Delphi survey of physicians, psychologists, and sports or physiotherapists
      in CR was conducted from April to July in 2016. The experts assessed several
      parameters of physical performance, social medicine, subjective health and
      cardiovascular risk factors regarding their suitability as performance measures
      of CR. RESULTS: Of the 44 predetermined as well as by the participants proposed
      parameters, 21 parameters (48%) were selected as potential performance measures.
      Half of these were psychosocial factors. Merely, smoking habits, blood pressure,
      LDL-cholesterol and maximum capacity on exercise-ECG achieved a consensus
      (agreement>75% of the respondents). CONCLUSIONS: The experts' choice of
      performance measures was little consistent. Therefore, a clinical investigation
      and scientific evaluation of the predefined parameters is essential.

PMID- 29590694
TI  - ?

PMID- 29590695
TI  - [50th volume of the HaMiPla].

PMID- 29590696
TI  - Factors involved in the clinical profile of carpal tunnel syndrome.
AB  - : Clinical presentation of carpal tunnel syndrome may differ in relation to
      certain factors like sex, age, duration of symptoms and severity of compression.
      The objective of this study was an investigation into the hypothesis that several
      distinct factors are predictive of the clinical profile for the condition. The
      records of 1,117 patients: 909 women (81 %) and 208 men (19 %) with a mean age of
      63 years, were analysed. The whole group was divided into subgroups, depending on
      the variables analysed: sex, age, duration of the condition, severity of
      symptoms, severity of electrophysiological abnormalities and occurrence or lack
      of comorbidities. RESULTS: Of all the considered variables, the Levine symptom
      scores had the greatest impact on the condition's clinical profile: the higher
      scores the more severe pain, poorer sensation, weaker grip and worse hand
      function. Also, ages greater than 80 years had a significant negative effect on
      most of the considered parameters. None of the remaining analysed variables had a
      substantial impact on the clinical profile of the condition.

PMID- 29590697
TI  - [Concerning the Wrist-to-Forearm-Ratio of the Median nerve ultrasound is not a
      suitable method for assessing the success of a carpal tunnel release].
AB  - PURPOSE: The primary aim of the study was to analyze whether there is and - if so
      - how far a correlation between the clinical findings after carpal tunnel release
      (CTR) for carpal tunnel syndrome (CTS) and the Wrist-to-Forearm-Ratio (WFR) of
      the median nerve in ultrasound to answer is question whether the WFR can be used
      in controlling the operative result. PATIENTS AND METHODS: In a prospective study
      the clinical, electrophysiological, and sonographic data of 40 patients with CTR
      for CTS were collected preoperative and 3 and 9 months postoperative. The data of
      21 patients with 23 operated hands completing the study were analyzed. There were
      5 men and 16 women with an average age of 58 years. RESULTS: Neither a
      correlation between the clinical findings postoperative and the WFR nor the
      electrophysiological findings postoperative was found. CONCLUSION: Concerning the
      Wrist-to-Forearm-Ration of the Median nerve ultrasound is not a suitable method
      for assessing the success of a carpal tunnel release.

PMID- 29590698
TI  - [The effects of standardised cold and compression therapy on swelling, pain and
      functional outcome after division of the transverse carpal ligament in carpal
      tunnel syndrome].
AB  - OBJECTIVE: This prospective, randomised study examines the effect of standardised
      cold compression therapy on swelling, pain and functional outcome after division
      of the transverse carpal ligament in carpal tunnel syndrome in comparison to
      cooling alone. PATIENTS AND METHODS: Fifty patients for division of the
      transverse carpal ligament were randomised into two groups. In group 1,
      postoperative conventional cooling therapy was performed. Group 2 was given
      standardised cooling and compression therapy with the Cryo/CuffTM-system (3 * 10
      min twice daily). Follow-up examinations were performed on days 1, 8 and 21 after
      the operation. One patient in group 1 and 3 patients in group 2 could not be
      followed up. Test parameters were pain, swelling, mobility, strength, and the
      DASH and MHQ score. RESULTS: There were no significant differences between the
      two groups at any time point. CONCLUSION: In this study, no advantage could be
      demonstrated for standardised cooling and compression therapy with the
      Cryo/CuffTM-system in comparison with conventional cooling after division of the
      transverse carpal ligament.

PMID- 29590699
TI  - [Midterm results after sole percutaneous treatment for central impression
      fractures of the base of the middle phalanx].
AB  - PURPOSE: This study investigated the midterm results after sole percutaneous
      treatment for central depression fractures of the base of the middle phalanx.
      PATIENTS AND METHODS: 19 men and 2 women with an average age of 31.9 (18 - 57)
      years with a central depression fracture of the middle phalanx treated solely by
      intramedullary reposition with a bended K-wire and percutaneous K-wire fixation
      were followed on average of 13.2 (3 - 40) months. RESULTS: At the time of the
      last follow-up, all patients were able to pursue their previous occupational
      activity as well as their usual leisure activities and were painfree (VAS 0). The
      postoperative active flexion of the affected PIP joint was 86 degrees  with an
      average extension deficit of 1 degrees  or 93 % of the range of motion of the
      uninjured PIPJ of the opposite side. Radiologically there was a nice remodeling
      of the articular surface with no osteoarthrosis. There were no pin-associated
      complications or wound healing disorders. CONCLUSION: The sole intramedullary
      reduction with K-wire osteosynthesis is a suitable and reliable method for the
      treatment of the central impression fracture. Good functional results can be
      achieved with low surgical effort.

PMID- 29590701
TI  - A case of severe gouty tophi-induced carpal tunnel syndrome: Operative finding
      and its outcome.
AB  - Gout is a disease featuring acute arthritis, joint deformity and severe pain
      caused through the deposition of monosodium urate crystals in and around synovial
      tissue 1. Tophi are stone-like deposits of monosodium urate in the soft tissues,
      synovial tissues, or bones adjacent to the joints. The tophi can compromise joint
      motion and deteriorate bony structure, finally leading to functional disability.
      Therefore, early treatment using uric acid lowering agents is standard practice
      in gout patients to prevent the formation of tophi through controlling uric acid
      levels.

PMID- 29590700
TI  - [Results of the reconstruction of the middle phalangeal base of the finger
      through an osteochondral autograft from the hamate bone].
AB  - OBJECTIVE: The fractured base of the middle phalanx was reconstructed in 13
      patients using an osteochondral transplant from the carpometacarpal joint surface
      of the hamate bone. The goal was to restore joint stability with preservation of
      mobility. Indications were acute and missed isolated destruction of the palmar
      middle phalanx base >= 30 %. Contraindications were destruction of the head of
      the proximal phalanx, advanced chondropathy of the head of the proximal phalanx,
      and extensive soft tissue injury with loss of skin coverage for the proximal
      interphalangeal joint. SURGICAL TECHNIQUE: In this procedure the fractured middle
      phalangeal base was debrided and the defect replaced by a size-matched autograft
      from the dorsal carpometacarpal osteoarticular surface of the hamate bone, which
      was secured in place with miniscrews. RESULTS: Bone fusion was achieved in 100 %
      with restoration of joint congruity in 12 of 13 cases and a slight subluxation in
      one case. Follow-up was possible in 9 cases after 23 (5-51) months. The average
      range of motion in the reconstructed joint for extension/flexion was 0/9/73
      degrees ; grip strength was 82 % of the unaffected side. Five out of 9 patients
      developed a mild flexion contracture in the PIP joint. The DASH score was 6 (0
      33) points, pain at rest was 1 (0-5), and pain at exercise 2 (0-6) on a visual
      analogue scale from 0-10. All patients were satisfied and willing to undergo the
      procedure again. According to the literature, reconstruction of the base of the
      middle phalanx by an osteochondral graft from the hamate bone is a reliable
      procedure to restore stability and mobility of the joint.

PMID- 29590702
TI  - [Rice bodies - an impressive diagnostic finding in chronic tenosynovitis].

PMID- 29590703
TI  - [Osteitis fibrosa cystica in the hand: a rare, but important differential
      diagnosis].

PMID- 29590704
TI  - Multiple aneurysme in the distal part of the A. ulnaris in a 8 years old boy.

PMID- 29590705
TI  - Hypothenar hammer syndrome.
AB  - In 1934 von Rosen first described a posttraumatic thrombosis of the distal ulnar
      artery resulting from blunt a trauma to the hypothenar region. But it was Conn in
      1970 who named it the "hypothenar hammer syndrome (HHS)" 1-2.

PMID- 29590706
TI  - [Tumor of the flexor tendon of the finger- a compelling case?]

PMID- 29590707
TI  - ?

PMID- 29590708
TI  - Principles of Orthopedic Infection Management.

PMID- 29590709
TI  - Erythropoietin in the Evaluation of Treatment Outcomes in Patients with
      Polytrauma.
AB  - Polytrauma is a term describing patients with injuries involving multiple body
      regions that compromises function of the body and/or organ involved. The aim of
      the study was to evaluate the potential role of erythropoietin in predicting
      poorer outcome in trauma patients. This prospective study included 86 patients
      admitted to the Emergency Center of Serbia due to polytrauma assigned according
      to Injury Severity Score (ISS). The patients were further evaluated using the
      Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure
      Assessment scores and erythropoietin levels. There was a significant difference
      among erythropoietin levels at admission, after 48 and 72 hours, and on day 7 of
      hospital stay, with significantly higher levels in patients with ISS values 49
      75. Based on the results, ROC curves were used to identify cut-off levels to
      predict ISS score with critical clinical course. It was concluded that
      erythropoietin could be a good marker of injury severity. Further research has to
      be performed to determine the cut-off values of erythropoietin that are
      significant for injury severity.

PMID- 29590710
TI  - Clinical Significance of VEGF-A and Microvessel Density in Diffuse Large B-Cell
      Lymphoma and Low-Grade Follicular Lymphoma.
AB  - Angiogenesis is essential for the development, growth and progression of tumors.
      Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic
      factor, its impact on lymphoma has not yet been fully clarified. The aim of this
      study was to evaluate VEGF-A -expression and microvessel density (MVD) in
      aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent
      lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive
      follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL,
      30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing
      density of blood vessels, as well as the total number of CD31 positive
      endothelial cells. The results were compared with relevant clinical data. MVD was
      85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was
      significantly higher in DLBCL than in low-grade FL and FH. A statistically
      significant association of MVD and VEGF-A with the International Prognostic Index
      (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL
      patients with high IPI, while there was no statistically significant association
      between MVD and VEGF-A with the Follicular Lymphoma International Prognostic
      Index in low-grade FL. Our results suggested an important relationship between
      angiogenesis and high-grade lymphoma.

PMID- 29590711
TI  - Position of Mandibular Condyles during Stabilization Splint Wearing.
AB  - The purpose of this study was to determine the position of mandibular condyles
      during wearing of stabilization splints with different thickness. Two
      stabilization splints were made for 10 completely dentate participants. First
      splint was made with minimal 1 mm distance at molar area between the upper and
      lower teeth, while the second splint was made 3 mm higher than the first splint.
      Condylar position measurements during splint wearing were done using ultrasound
      jaw tracking device with six degrees of freedom at the antero-posterior (x),
      vertical (y) and lateral (z) axes. Linear deviation values were calculated from
      the values of the Cartesian coordinate system. The mean value of linear deviation
      between the habitual occlusion and the occlusion with stabilization splint made
      at 1 mm distance in molar area was 2.04+/-1.18 mm, while with stabilization
      splint made 3 mm higher than the first one it was 2.32+/-1.24 mm. Independent
      samples T test did not confirm statistically significant difference in deviation
      values between the splints of different thickness. Raising stabilization splint
      height does not change significantly the position of the condyle within the
      temporomandibular joint. Higher condylar distraction in the temporomandibular
      joint cannot be expected with 'thicker' stabilization splint.

PMID- 29590712
TI  - Analysis of Airborne Dust as a Result of Plaster Cast Sawing.
AB  - Plaster splints are used daily in surgical and orthopedic fields in order to
      immobilize injured children and adults. The aim of this study was to measure the
      aerodynamic diameter and concentration of dust particles in the air caused by
      sawing plaster splints (calcium sulfate dehy-drate). We performed fractional
      measurements of airborne dust particles. The measured particles, which can
      potentially be inhaled, may have a specific negative effect on human health.
      Measurements were conducted in laboratory research facilities that simulated
      hospital conditions within a casting room and the associated waiting room.
      Measurements within the casting room were made using two particle collector
      devices and one laser photometer. The measurement for the simulated waiting room
      was performed using the same principles and devices. The collected plaster dust
      particles differed in aerodynamic diameter and concentration according to the
      various locations observed. The highest concentration of particles of all sizes
      was recorded at the site of cast sawing. There was direct correlation between
      distance from the source and concentration of airborne particles; this
      concentration was lowest in the waiting room. The concentrations of plaster dust
      recorded were lower than the recommended minimal limit values for total and
      respiratory fractions in Croatia. Accordingly, it can be assumed that sawing of
      plaster splints has no harmful health effects on the exposed patients and health
      personnel.

PMID- 29590713
TI  - Structure-Function Relationship of Changes in Visual Field Indices with Quadrant
      and Average Retinal Nerve Fiber Layer Thickness in the Eyes with Exfoliation.
AB  - The progressive nature of glaucoma suggests it should be possible to detect
      structural changes such as retinal nerve fiber layer (RNFL) thickness loss before
      the condition becomes clinically apparent with visual field (VF) impairment.
      Therefore, the aim was to analyze RNFL thickness and VF changes in study groups
      with unilateral exfoliation syndrome (XFS), bilateral XFS and bilateral
      exfoliative glaucoma (XFG), and compare it with controls. The study included 114
      subjects (228 eyes) divided into 4 groups according to the presence of
      exfoliation: 30 subjects with unilateral XFS (30 with clinically visible XFS and
      30 fellow eyes), 24 subjects (48 eyes) with bilateral XFS, 28 (56 eyes) subjects
      with bilateral XFG, and control group (32 subjects). All subjects underwent VF
      and RNFL measurements after ophthalmologic examination. Both eyes of unilateral
      XFS (clinically -visible and fellow eye) showed positive correlation between Mean
      Defect (MD) and square root of Loss of Variance (sLV) and between MD and inferior
      quadrant RNFL thickness. In bilateral XFS and XFG, there was negative correlation
      between MD and inferior quadrant RNFL thickness. Inferior, superior and nasal
      quadrant RNFL thickness was lower in XFG group than in other groups. In bilateral
      XFS group, the inferior quadrant RNFL thickness was lower as compared with
      unilateral XFS group (in both eyes). The mean RNFL thickness negatively
      correlated with MD in bilateral XFS and XFG groups. In conclusion, structural
      changes before VF impairment have an important role in early detection of
      glaucoma in subjects at risk.

PMID- 29590714
TI  - Manual Intracardiac Electrogram Method Is Accurate Alternative to
      Echocardiography for Atrioventricular and Interventricular Optimization in
      Cardiac Resynchronization Therapy.
AB  - Some manufacturers do not provide automated intracardiac electrogram method
      (IEGM) systems for atrioventricular (AV) and interventricular (VV) delay
      optimization in cardiac resynchronization therapy (CRT). We aimed to evaluate the
      accuracy of manual IEGM method in 48 patients previously implanted with Medtronic
      Syncra CRT. All patients underwent standard device interrogation followed by CRT
      optimization by IEGM method and by echocardiography one month after implantation.
      The patient mean age was 60.7+/-11.8 years and there were 33 (68.8%) males. After
      CRT implantation, the left ventricular ejection fraction increased from 28.0+/
      7.9% to 39.1+/-11.0% (p<0.001). Optimal aortic flow Velocity Time Integral (aVTI)
      was obtained when VV was set to 20-50 ms left ventricular pre-activation. There
      was a strong correlation between VV values determined by echocardiography and
      IEGM (R=0.823, p<0.001). We found no significant difference in AV, VV and aVTI
      values between echocardiography and IEGM method. However, IEGM was significantly
      less time-consuming than echocardiography [20 (10-28) vs. 40 (35-60) minutes,
      p<0.001]. Manual IEGM method may be good alternative to echocardiography and
      automated IEGM method. It also emphasizes the need for implementation of
      automated IEGM systems in as many CRT devices as possible.

PMID- 29590715
TI  - Nutritional Status and Nutrition Quality in Patients with Non-Alcoholic Fatty
      Liver Disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is becoming a major health burden with
      increasing prevalence worldwide due to its close association with the epidemic of
      obesity. Currently there is no standardized pharmacological treatment, and the
      only proven effective therapeutic strategy is lifestyle modification, therefore
      it is important to determine the potential dietary targets for the prevention and
      treatment of NAFLD. We assessed nutritional status in 30 patients diagnosed with
      NAFLD using anthropometric parameters, hand grip strength, and lifestyle and
      dietetic parameters (physical activity, NRS2002 form and three-day food diary).
      The mean body mass index was 29.62+/-4.61 kg/m2, yielding 86.67% of obese or
      overweight patients. Physical activity results indicat-ed poorly active subjects.
      Excessive energy intake was recorded in 27.78% of patients. The mean in-take of
      macronutrients was as follows: 15.5% of proteins, 42.3% of carbohydrates and
      42.2% of fat, with -deficient micronutrient intake of calcium, magnesium, iron,
      zinc, and vitamins A, B1 and B2. The -results showed that the quality of
      nutrition in study subjects was not accordant to current rec-ommendations and
      that they consumed a high proportion of fat, especially saturated fatty acids,
      along with low micronutrient intake. The results obtained might point to the
      importance of unbalanced diet as a contributing factor in NAFLD development.

PMID- 29590716
TI  - The Role of Endothelial Dysfunction in the Mechanism of Gastroesophageal Reflux
      Disease Development in Patients with Ischemic Heart Disease.
AB  - Ischemic heart disease (IHD) and gastroesophageal reflux disease (GERD) are among
      the most common diseases worldwide, which in a considerable percentage of cases
      occur together, thus complicating symptoms, posing problems for timely diagnosis
      and hindering development of a comprehensive treatment regimen for both diseases.
      Research has shown that endothelial dysfunction is one of the major
      pathophysiological mechanisms in the development of IHD. Endothelial dysfunction
      also affects regional perfusion of the esophagus, thus compromising esophageal
      tissue defense mechanisms. The aim of our study was to investigate the role of
      endothelial dysfunction in the mechanisms of GERD development in patients with
      IHD. For the purpose of this study, we collected data on serum levels of
      endothelin-1, nitric oxide metabolites and lipid peroxidation products, gastric
      pH, parameters of regional blood flow, and quality of life assessment. Study
      results revealed that in IHD patients with concomitant GERD, endothelial
      dysfunction manifested by a significant increase in the levels of endothelin-1
      and lipid peroxidation products, with decreased levels of nitric oxide
      metabolites, regional blood flow and quality of life. These findings suggest that
      hypoxia of the esophageal mucosa, caused by endothelial dysfunction, leads to a
      decrease in the esophageal tissue resistance and to esophageal lower sphincter
      dysfunction, which, in turn, are the leading factors in the development of GERD.

PMID- 29590717
TI  - A Retrospective Study of Discordant Twin Growth in Dichorionic Twin Pregnancies
      and Risk of Preterm Delivery at Split University Hospital Centre: Three-Year
      Experience.
AB  - The aim was to determine whether discordant twin growth has an impact on preterm
      birth in dichorionic pregnancies. This retrospective study included dichorionic
      twin pregnancies in the period from January 1, 2013 to December 31, 2015. The
      following variables were investigated: maternal age (years), parity, body mass
      index (kg/m2), week (<=366/7 and >=37) and mode of delivery (vaginal and cesarean
      section), birth weight (grams) and Apgar score (<=7, 8-10). Discordant twin
      growth in dichorionic pregnancies was found to be associated with preterm birth
      (chi2=4.74; p=0.03) but had no impact on the mode of delivery (chi2=0.119;
      p=0.73). There was a statistically significant difference in the rate of small
      for gestational age (SGA) neonates (chi2=16.4556; p=0.000267) and Apgar score
      (chi2=7.9931; p<0.05) between the study groups. Mode of conception in dichorionic
      pregnancies was not a risk factor for preterm delivery (chi2=1.417; p=0.23). In
      conclusion, discordant twin growth in dichorionic pregnancies is a risk factor
      for preterm delivery and has no impact on the mode of delivery but has an impact
      on the rate of SGA and Apgar score.

PMID- 29590718
TI  - Analysis of the Hemoglobin Level Drop in Patients with Hip Fracture After
      Admission.
AB  - The studies that evaluated blood loss during hip surgery found a relatively small
      loss that does not explain the large hemoglobin drop postoperatively. The aim of
      this study was to determine the fall in hemoglobin level after admission and
      rehydration in patients with hip fractures and to identify the patients that need
      blood transfusion. This retrospective study included data on 374 patients with
      hip fracture with surgery delayed by more than 24 hours and complete blood count
      repeated prior to surgery after fluid resuscitation for a minimum of 24 hours.
      The hemoglobin level (g/L) was analyzed after admission and after rehydration.
      The results were compared by Student's t-test. The mean hemoglobin drop was 6.1
      g/L, 12.05 g/L and 16.52 g/L for capsular, pertrochanteric and subtrochanteric
      fractures, respectively. This hemoglobin drop was statistically significant in
      all frac-ture types. The significant drop of preoperative hemoglobin should be
      taken in consideration when planning transfusion for hip fracture patients.
      Collection of blood sample after rehydration preopera-tively would enable prompt
      diagnosis and treatment of anemia in these patients, along with proper
      transfusion planning and cross-matching.

PMID- 29590719
TI  - Effect of Smelling Amniotic Fluid on Comfort and Crying in Preterm Infants During
      Peripheral Cannulation: A Randomized Controlled Trial.
AB  - The aim of the study was to investigate the effect of smelling amniotic fluid on
      comfort and duration of crying caused by peripheral cannulation in preterm
      infants. This was a randomized controlled trial. The study sample consisted of 80
      preterm infants meeting the case selection criteria. The infants were randomly
      assigned to experimental and control group. Upon exclusion of some infants from
      the study, total number of infants in both groups was 61. The infants in the
      amniotic fluid group smelled amniotic fluid for 15 minutes before, during, and
      for 15 minutes after the ap-plication of peripheral cannulation, whereas the
      infants in the control group did not undergo any in-tervention other than routine
      care. The level of comfort was significantly higher and the duration of crying
      lower in the infants from the amniotic fluid group as compared with control group
      before, during and after the procedure. The intervention of smelling amniotic
      fluid was found to be an effective practice that could be used for reducing the
      length of crying and increase comfort in preterm infants undergoing peripheral
      cannulation.

PMID- 29590720
TI  - Implementation of Venous Thromboembolism Prophylaxis Guidelines in Clinical
      Practice: A Retrospective Study in Two Croatian Hospitals.
AB  - The aim of this study was to evaluate the implementation of the 9th edition of
      the American College of Chest Physicians (ACCP9) guidelines for prevention of
      venous thromboembolism in nonsurgical patients in clinical practice in one
      university and one general Croatian hospital. A retrospective study was conducted
      at Zadar General Hospital from Zadar and Dubrava University Hospital from Zagreb.
      Medical charts of all patients admitted to Medical Departments in two periods,
      before and after implementation of the ACCP9 guidelines, were analyzed. The ACCP9
      guidelines were made available to all physicians through the hospital electronic
      information system immediately after the publication. The Hospital Drug
      Committees promoted implementation of the guidelines during their periodical
      clinical visits. Overall, 850 patients were included in the study in two periods.
      There was no statistically significant difference in the number of high-risk
      patients receiving thromboprophylaxis after the guidelines implementation in
      either hospital. In both periods, a signifi-cantly higher number of high-risk
      patients received thromboprophylaxis in Dubrava University Hos-pital in
      comparison with Zadar General Hospital (31.7% vs. 3.8% and 40.3% vs. 7.3%,
      respectively; p<0.001). This study revealed insufficient implementation of
      evidence-based thromboprophylaxis guidelines in clinical practice in two Croatian
      hospitals.

PMID- 29590721
TI  - Chemerin Blood Levels are Associated with MRI Measured Volumes of Abdominal
      Adipose Tissue Compartments and Lifestyle Choices.
AB  - Obesity is a low-grade chronic inflammatory state, in which a cytokine chemerin
      with its immunometabolic modulation has an important role. We aimed to study in a
      healthy population relationships between serum chemerin levels, lifestyle choices
      and magnetic resonance imaging (MRI) assessed volumes of abdominal visceral (VAT)
      and subcutaneous (SAT) adipose tissues, which have different cytokine expression
      profiles. Overall, 73 healthy participants undertook lifestyle questionnaire and
      underwent anthropometric measurements along with MRI scanning of abdominal SAT
      and VAT. Furthermore, complete blood count was determined along with chemerin and
      fibrinogen serum levels. Regression model for prediction of chemerin serum levels
      was built after controlling for sex, age and anthropometric measures. Median
      serum chemerin was 141 (125-195) ng/mL. Serum chemerin had a moderate positive
      correlation with SAT and VAT volumes. The two most important predictors of
      chemerin levels were MRI detected SAT and thigh circumference. Independently,
      chemerin levels were associated with smoking, preference of salty food, and
      favoring flavor/simplicity of preparation over nutritional value of the food.
      Serum chemerin seems to be more strongly correlated with the volume of abdominal
      SAT than VAT, with certain lifestyle choices influencing chemerin levels
      independently of abdominal fat.

PMID- 29590722
TI  - Association of Pentraxin-3, Galectin-3 and Matrix Metalloproteinase-9/Timp-1 with
      Cardiovascular Risk in Renal Disease Patients.
AB  - Inflammation, apoptosis and extracellular remodeling play significant roles in
      cardiovascular disease (CVD) underlying the major causes of mortality in renal
      patients. In 19 pre-dialysis patients, 21 dialysis patients and 20 control
      subjects, the concentrations of pentraxin-3, galectin-3, MMP-9 and TIMP-1 were
      determined by ELISA. CVD risk was calculated according to the Framingham risk
      score algorithm. Pentraxin-3 was increased in renal patients compared to healthy
      controls (p<0.001). In contrast, galectin-3 was reduced in hemodialysis patients
      compared to pre-dialysis patients and controls (p<0.001). In addition, MMP-9 and
      TIMP-1 were elevated in renal patients compared to controls (p<0.01 and p<0.001,
      respectively). Logistic regression analyses disclosed associations of galectin-3,
      MMP-9, pentraxin-3 and glomerular filtration with calculated CVD risk score.
      Combined testing of pentraxin-3, galectin-3, MMP-9 and glomerular filtration rate
      can discriminate renal patients with high and low risk of a coronary event.

PMID- 29590723
TI  - Business Performance of Health Spa Tourism Providers in Relation to the Structure
      of Employees in the Republic of Croatia.
AB  - Health spa tourism services are provided in special hospitals for medical
      rehabilitation and health resorts, and include controlled use of natural healing
      factors and physical therapy under medical supervision in order to improve and
      preserve health. Health tourism is a service industry and therefore labor
      intensive industry in which human resources are one of the key factors of
      business success. The aim of this study was to analyze business performance of
      special hospitals for medical rehabilitation and health resorts in Croatia in
      relation to the structure of employees, specifically the number of physicians and
      total medical personnel, as well as the share of physicians and medical personnel
      in the total number of employees. The assumption was that those who employ more
      physicians and medical employees are more successful. The empirical research was
      conducted and the assumption was tested firstly by correlation analysis and
      afterwards by regression analysis. The total number of employees in the
      researched health resorts and special hospitals amounted to 2,863, of which the
      share of physicians specialists accounted for almost 7%, while the share of total
      medical staff was almost 53%. From the results of our research, it can be
      concluded that special hospitals for medical rehabilitation and health resorts,
      which employ more physicians and medical personnel, are achieving better
      financial business performance. Based on the results obtained, it is possible to
      provide guidance for further growth and development in the direction of basing
      the primary offer on medical-health offer, rather than on wellness offer, which
      is a strong trend in the world. These findings are important for planning the
      health and tourism policies in Croatia and similar countries.

PMID- 29590724
TI  - Comparing Diagnostic Accuracy of Direct Questioning Versus Schematic Evaluation
      of Chronic Pain Localization.
AB  - None of the previous studies localized pain in comparison with graphic scheme.
      Our aim was to investigate the validity of direct questioning about the main pain
      localization in comparison with schematic evaluation. In this cross-sectional
      study, 331 patients, mean age 49.4+/-10.72 years, localized their main pain site
      anatomically with manikin and by direct questioning. Two methods were employed to
      localize pain: direct questioning and schematic evaluation (manikin).
      Sensitivity, specificity, accuracy, positive predictive value (PPV), negative
      predictive value (NPV), positive likelihood ratio (PLR), negative likelihood
      ratio (NLR) and odds ratio (OR) were used to compare these two methods. Study
      patients answered in both methods. The sensitivity and PPV were mostly in a weak
      range, while accuracy, specificity and NPV were mostly in good range. Kappa index
      was in the marginal reproducibility range. Pain in the left part of the body had
      a higher OR (OR=9). PLR for pain in the right part of the body was 28.03. NLR for
      all questions was located in the small and rarely important change probability
      group. Negative answer in direct questioning was more reliable than a positive
      one. Pain localization in the left side of the body was more reliable.

PMID- 29590725
TI  - Nutritional Issues and Nutrition Support in Older Home Care Patients in the City
      of Zagreb.
AB  - Population aging is a global demographic trend showing continuous growth and
      among its consequences is a rise in malnutrition that is characteristic for the
      elderly. The objective of this study was to evaluate nutritional status of
      elderly home care patients immediately after hospital discharge and to determine
      factors that affect nutritional status using questionnaires based on validated
      tools (NRS-2002, DETERMINE checklist) and basic medical history data. The study
      involved 76 elderly individuals (51.3% of them older than 70) living in the City
      of Zagreb. The nutritional status assessment using the NRS-2002 tool showed that
      57.6% of the subjects were at nutritional risk. The findings of the assessment by
      use of the DETERMINE tool were also unfavorable, indicating that 82.1% of persons
      older than 70 were categorized as being at a high nutritional risk, while 17.9%
      were at moderate risk. The DETERMINE checklist elements (illness; reduced intake
      of fruits, vegetables or dairy products; alcohol consumption; oral health
      problems; and weight loss) were linked to a higher NRS score. The mean number of
      hospital days in subjects at nutritional risk was 14.27 (the mean number in the
      Republic of Croatia is 8.56 days). Although the study involved a small number of
      subjects, the results showed a substantial presence of malnutrition among the
      elderly. A timely -intervention by the healthcare system and training of
      healthcare personnel can be a step towards achieving a better nutritional status.

PMID- 29590726
TI  - Bleeding Peptic Ulcer - Tertiary Center Experience: Epidemiology, Treatment and
      Prognosis.
AB  - The aim of this study was to demonstrate epidemiological, clinical and endoscopic
      characteristics of acute upper gastrointestinal bleeding (UGIB) with special
      reference to peptic ulcer bleeding (PUB). The study included 2198 consecutive
      patients referred to our emergency department due to acute UGIB from January 2008
      to December 2012. All patients underwent urgent upper GI endoscopy within 24
      hours of admission, and 842 patients diagnosed with PUB were enrolled and
      prospectively followed-up. The cumulative incidence of UGIB was 126/100,000 in
      the 5-year period. Two out of five patients had a bleeding peptic ulcer; in
      total, 440 (52.3%) had bleeding gastric ulcer, 356 (42.3%) had bleeding duodenal
      ulcer, 17 (2%) had both bleeding gastric and duodenal ulcers, and 29 (3.5%)
      patients had bleeding ulcers on gastroenteric anastomoses. PUB was more common in
      men. The mean patient age was 65.9 years. The majority of patients (57%) with PUB
      were taking agents that attenuate the cytoprotective function of gastric and
      duodenal mucosa. Rebleeding occurred in 77 (9.7%) patients and 47 (5.9%) patients
      required surgical intervention. The 30-day morality was 5.2% and 10% of patients
      died from uncontrolled bleeding and concomitant diseases. In conclusion, PUB is
      the main cause of UGIB, characterized by a significant rebleeding rate and
      mortality.

PMID- 29590727
TI  - Nonverbal Memory Capacity in Persons with Epilepsy Is Associated with Depression
      Rather than Anxiety.
AB  - Epilepsy is characterized by repeated epileptic seizures, which are manifested in
      various ways and depend on the location and size of foci in the brain. Long-term
      seizures with secondary generalization can cause memory problems. Numerous
      studies demonstrate the connection of memory damage and lateralization in medial
      temporal lobe epilepsy (TLE). However, the results were not always consistent
      with the material-specific memory model. A possible explanation for these
      inconsistent data is the insufficient control of psychological variables that can
      affect memory. In most of the previous studies in persons with epilepsy, they
      were not controlled for their emotional states such as anxiety and depression. We
      used the Rey Complex Figure Test (RCFT) as a measure of visual memory, Beck's
      depression inventory as a measure of depressive symptoms, and the State-Trait
      Anxiety Inventory as a measure of anxiety in 57 consecutive participants. Our aim
      was to investigate whether there is difference in visual memory with respect to
      the left and right TLE, and whether the participants of different gender with
      higher anxiety and depression rates would achieve different results on visual
      memory. Persons with lower levels of depression achieved better scores in the
      Immediate and Delayed recall subtests of the RCFT. We also explored the potential
      gender differences. Testing differences between the persons with higher and lower
      anxiety levels did not reveal any significant differences in any of the measures
      tested.

PMID- 29590728
TI  - Diabetic Polyneuropathy and Risk of Falls: Fear of Falling and Other Factors.
AB  - The aim of the study was to analyze postural stability, walking speed and fear of
      falling in patients with diabetic polyneuropathy (DPN) in order to determine the
      risk factors for falls, as well as the effect of DPN characteristics as
      additional factors. A sample of 48 patients with type 2 diabetes and DPN were
      enrolled in this non-randomized observational study. The patients were divided
      into two groups of fallers and non-fallers. All subjects underwent evaluation
      with the Functional Reach Test (FRT), Tinetti Falls Efficacy Scale (Tinetti FES)
      and 10-Meter Walk Test (10MWT). Neuropathy was quantified with the Michigan
      Neuropathy Screening Instrument (MNSI, Questionnaire part) and 5.07/10-g Semmes
      Weinstein monofilament examination (SW-ME). The 10MWT and SW-ME were
      significantly different between the faller and non-faller groups (p<0.05).
      Duration of DPN correlated positively with SW-ME (p=0.005) in the faller group.
      FES showed significant positive correlation with MNSI and negative correlation
      with 10MWT in the non-faller group. Logistic regression analysis revealed that SW
      ME was significantly associated with the probability of falling (p=0.0076;
      OR=1.378). Study results suggested that the loss of protective sensitivity of
      foot could be a risk factor for falls in people suffering from type 2 diabetes.

PMID- 29590729
TI  - Determination of Predictive Anatomic Parameters for Bleeding of Brain
      Arteriovenous Malformations by Multidetector CT Angiography.
AB  - Patients with brain arteriovenous malformation (AVM) have a certain risk to
      bleed, and the goal of this study was to examine the effect of radiological and
      clinical predictive characteristics of AVM hemorrhage using multidetector
      computed tomographic (MDCT) angiography. The study included a series of 57
      patients, mean age 35.46 years, who were diagnosed during their hospitalization
      at Clinical Department of Neurosurgery, Clinical Center of Serbia, in the period
      from January 2008 to March 2016. In all patients, the diagnosis was made using
      MDCT angiography. Two groups of patients were observed. The first group included
      patients who did not initially present with hemorrhage, while the second group
      initially presented with hemorrhage. Both groups were treated with medical
      therapy or a combination of medical therapy with
      embolization/surgery/radiotherapy. Deep venous drainage (p<0.05), combined
      arterial supply from different basins (p<0.05) with a length <60 mm, venous
      dilatation present in the drainage vein (p<0.01), and the angle of casting sup
      ply arteries in the nidus (p<0.01) carry a risk of repeated bleeding. In the
      group of patients who had initial hemorrhage, the mean value of the casting angle
      size was 130 degrees , while in the group that did not have initial bleeding the
      mean value of the measured angle size was 103.81 degrees  with standard deviation
      of 17.21 degrees  (p<0.01). In conclusion, AVMs with deep venous drainage from
      the carotid and vertebrobasilar basin, the length of the feeding arteries <60 mm,
      the angle of the casting feeding arteries in the nidus >=130 degrees  and
      dilatation and/or venous aneurysm of drainage vessel are predictive for clinical
      presenting by hemorrhage.

PMID- 29590730
TI  - Serum Osteoprotegerin in Patients with Calcified Aortic Valve Stenosis in
      Relation to Heart Failure.
AB  - The aim of the study was to assess the role of serum osteoprotegerin (OPG) as a
      biomarker in patients with aortic valve stenosis (AS) in relation to heart
      failure and symptomatic status. This was a case control study, which included 51
      patients with AS and 39 control subjects. At the time of study enrolment,
      detailed medical history was obtained and all subjects underwent physical
      examination, chest x-ray and echocardiography. OPG levels were measured in all
      subjects, and serum N-terminal of the pro b-type natriuretic peptide (NT pro BNP)
      levels were determined in patients with AS. Serum OPG levels were elevated in
      patients with AS compared to control subjects (p=0.001). Patients with heart
      failure due to AS had elevated serum OPG levels in comparison to patients without
      heart failure (p=0.001). A significant correlation between OPG and symptomatic
      status was observed in all patients with AS (p<0.001), however, it was not the
      case in patients without heart failure (p=0.425). There was a positive
      correlation between OPG and NT pro BNP concentrations with objective signs of
      heart failure on chest x-ray (p<0.001). Negative correlation of OPG
      concentrations with aortic valve area was present (p<0.040), as well as with left
      ventricular ejection fraction (p<0.001). Serum OPG could be a valuable biomarker
      in the evaluation of severity of calcified AS and serve as an additional
      indicator besides clinical presentation and echocardiography in the assessment of
      surgical treatment or aortic valve replacement.

PMID- 29590731
TI  - Parental Socioeconomic Status as a Predictor of Physical and Mental Health
      Outcomes in Children - Literature Review.
AB  - Parental socioeconomic status is a multidimensional concept of special importance
      for the growth, development, health outcomes and education of children. Its
      definition generally refers to the amount of parents' income, their employment
      status and level of education. Hence, lack of economic resources and poverty of
      parents affect all aspects of the child's life, health outcomes and education, as
      well as his/her social inclusion. Accordingly, the consequences of a reduced
      parental socioeconomic status leave long-term effects on their children.
      Therefore, in order to create interventional programs for children of parents
      with low income and lower socioeconomic status, as well as with lower level of
      education, it is important to address the direct aspects of poverty. This review
      contributes to the evidence indicating that the parental socioeconomic status is
      highly influential in determining the child's physical and mental health and
      future outcomes including his/her academic achievements and education, as well as
      the parameters of his/her physical abilities, cognitive function and fundamental
      neurobiology affecting brain development.

PMID- 29590732
TI  - Genetic Aspects of Hereditary Arrhythmogenic Syndromes in Children and Adults.
AB  - Recent research has revealed the genetic etiology of a number of heart diseases
      that cause sudden cardiac death. Lethal channelopathies are of great importance
      among the genetically determined heart diseases. Their basic characteristics are
      unpredictable and deadly nature, autosomal dominant inheritance with variable
      expressivity and incomplete penetrance in structurally normal heart, and absence
      of morphological and histological clues that a standard autopsy can identify.
      Minimum screening of the relatives of sudden cardiac death victims involves
      taking medical history, physical examination, electrocardiography,
      echocardiography, and exercise testing. Total positivity of classic genetic tests
      is only 15%-25%. Even the next generation sequencing technology does not provide
      a positive result of genetic testing in more than 35% of cases. Therefore, it is
      necessary to identify a larger number of genes the presence of which can lead to
      sudden cardiac death, to reduce the number of false positive results, and point
      to the importance of conducting genetic testing of young victims of sudden
      cardiac death. Until then, it is enough to preserve 5 g of fresh heart tissue of
      sudden cardiac death victims at a temperature of -80  degrees C. The material can
      be analyzed years later without losing its actuality because it contains
      information important for the next generation of the sudden cardiac death victim
      relatives.

PMID- 29590733
TI  - Role of Vestibular Evoked Myogenic Potentials as an Indicator of Recovery in
      Patients with Benign Paroxysmal Positional Vertigo.
AB  - Ocular vestibular evoked myogenic potentials (oVEMP) and cervical VEMP (cVEMP)
      are newer diagnostic methods, which allow an insight into the otolith senses. Our
      aim was to determine changes in certain parameters of the VEMP wave complex after
      successfully performed repositioning procedure, as an indicator of the state of
      recovery in patients with benign paroxysmal positional vertigo (BPPV). This may
      confirm the theory of otolith returning into the area of otolithic senses. The
      study included 48 patients with unilateral posterior semicircular canal BPPV. On
      their first arrival, otoneurological examinations, oVEMP and cVEMP tests were
      performed. The same were included in follow up check-ups scheduled at seven days
      and six months after successful implementation of Epley maneuvers. The initial
      measurement revealed a significantly reduced amplitude of oVEMP on the affected
      side. On the 7-day measurement, the amplitude increase was observed on the
      affected side, with significant reduction in the amplitude ratio (p=0.693), which
      reached statistical significance on the last measurement at 6 months (p=0.006).
      These findings confirmed the hypothesis of the return of otoconia into the
      utricular area.

PMID- 29590734
TI  - A Comparative Study of Data Collection Methods in the Process of Nursing:
      Detection of Chemotherapy Side Effects Using a Self-Reporting Questionnaire.
AB  - Ocular vestibular evoked myogenic potentials (oVEMP) and cervical VEMP (cVEMP)
      are newer diagnostic methods, which allow an insight into the otolith senses. Our
      aim was to determine changes in certain parameters of the VEMP wave complex after
      successfully performed repositioning procedure, as an indicator of the state of
      recovery in patients with benign paroxysmal positional vertigo (BPPV). This may
      confirm the theory of otolith returning into the area of otolithic senses. The
      study included 48 patients with unilateral posterior semicircular canal BPPV. On
      their first arrival, otoneurological examinations, oVEMP and cVEMP tests were
      performed. The same were included in follow up check-ups scheduled at seven days
      and six months after successful implementation of Epley maneuvers. The initial
      measurement revealed a significantly reduced amplitude of oVEMP on the affected
      side. On the 7-day measurement, the amplitude increase was observed on the
      affected side, with significant reduction in the amplitude ratio (p=0.693), which
      reached statistical significance on the last measurement at 6 months (p=0.006).
      These findings confirmed the hypothesis of the return of otoconia into the
      utricular area.

PMID- 29590735
TI  - Umbilical Cord Management and Stump Care in Normal Childbirth in Slovenian and
      Croatian Maternity Hospitals.
AB  - The aim was to investigate first-care procedures for the newborn's umbilical cord
      at maternity hospitals in Slovenia and Croatia. The study was based on an
      empirical survey research approach and quantitative research paradigms and
      included all Slovenian (n=14) and all Croatian (n=35) maternity hospitals.
      Leaders of midwifery team of 14 Slovenian and 35 Croatian labor wards were
      invited to participate. The study was conducted in 2013, with 67% of Slovenian
      and 66% of Croatian maternity hospitals having responded. A causal and non
      experimental method of empirical research was used. The research instrument was a
      questionnaire. Descriptive statistics was used on data analysis. The independence
      hypothesis was tested with the chi2-test or Kullback 2I-test. A vast ma-jority of
      study wards employed delayed umbilical cord clamping, i.e. clamping the cord
      after pulsa-tion had ceased. Only 10% of Slovenian in comparison with 36.4% of
      Croatian maternity hospitals practiced dry cord care. Others applied disinfectant
      on the cord, in Slovenia most frequently 6% po-tassium permanganate, and in
      Croatia a combination of octenidine and phenoxyethanol. Most Croa-tian -maternity
      wards (95.7%) still covered the stump, while it was not regular practice in
      Slovenia. The authors estimate that the prevailing Slovenian and Croatian
      practices in regard to cord clamping are in accordance with the evidence, while
      improvements could be made regarding stump care, since dry cord care is the
      recommended method.

PMID- 29590736
TI  - Incidence of Central Nervous System Tumors in Patients Hospitalized at Split
      University Hospital Centre During a Ten-Year Period (January 1, 2004 - December
      31, 2013).
AB  - The aim was to evaluate the incidence and characteristics of central nervous
      system tumors in patients hospitalized at the Department of Neurology, Split
      University Hospital Centre, during a 10-year period. The study included data on
      859 patients with the diagnosis of central nervous system (CNS) tumor. Diagnosis
      was based on the routine CNS neuroimaging methods (computed tomography/magnetic
      resonance imaging). Access to patient medical records provided demographic and
      clinical data, continued by collection of data on potential lethal outcome of
      patients at the Registrar's Office. The study was conducted at the Department of
      Neurology, Split University Hospital Centre, from January 1, 2004 to December 31,
      2013. There were 448 male and 411 female patients. Median age at the diagnosis
      was 65 (range, 18-95) years. Primary CNS tumors were diagnosed in 527 patients,
      including 30 primary recurrent tumors, whereas 328 patients had metastatic
      tumors; in 4 cases, it was impossible to determine whether the tumor was a
      primary one or metastasis based on CNS neuroimaging. The primary tumors proved to
      be more common than the metastatic ones (chi2-test, p<0.05). Multiple tumor
      transplants were more common than solitary (211 vs. 117; the conclusion was made
      at a 95% level of confidence; chi2-test, p<0.05). The majority of metastases
      originated from the lung (bronchus and pleura cancer; 46.41%; chi2-test, p<0.05;
      95% CI). The most common localization of CNS tumors was supratentorial. Based on
      the double-logarithmic model, we proved with statistical significance that there
      was an increase in the incidence of CNS tumors (p=0.001). The most common tumors
      studied were supratentorially localized meningiomas.

PMID- 29590737
TI  - Prevalence of Open Angle Glaucoma in Risk Groups in Slavonia and Baranya Region.
AB  - The aim of this prospective study was to detect primary open angle glaucoma
      (POAG) in its early stage in patients at a higher risk of its development, and to
      identify the risk group with the highest prevalence of POAG. The study was
      conducted at Department of Ophthalmology, Osijek University Hospital Centre, and
      included 250 patients divided into five groups, as follows: group 1, patients
      with diabetes type 1 and type 2; group 2, patients with arterial hypertension
      (blood pressure >140/90 mm Hg); group 3, patients with positive family history of
      POAG; group 4, patients with myopia between -3.0 and -8.0 diopters; and group 5,
      control group including patients aged 40 with no risk factors for POAG
      development. Study results showed that distribution of glaucoma patients was not
      equal across the groups. The prevalence of POAG in all patients was 5.6%, whereas
      in patients with positive family history of POAG it was 14%, which was
      statistically significantly higher than in patients with diabetes and myopia (4%
      both), as well as in control group. The difference was greatest in comparison to
      control group. There was no statistically significant difference in glaucoma
      incidence between the group of patients with positive family history (14%) and
      patients with systemic hypertension (6%). The results obtained suggest that of
      all risk factors analyzed, positive family history of POAG is the most important
      risk factor for glaucoma development in all risk groups.

PMID- 29590738
TI  - Effect of the Size of the Left Atrium on Sustained Sinus Rhythm in Patients
      Undergoing Mitral Valve Surgery and Concomitant Bipolar Radiofrequency Ablation
      for Atrial Fibrillation.
AB  - Atrial fibrillation is associated with systemic embolization and complications
      due to anticoagulant therapy. Radiofrequency ablation has been established as an
      effective and safe method for the treatment of atrial fibrillation. The aim of
      this study was to evaluate the effect of the size of the left atrium on the
      outcome of surgical radiofrequency ablation. Forty patients scheduled for
      elective mitral valve surgery and radiofrequency ablation were enrolled in the
      study. Group 1 consisted of patients with a left atrium diameter <=5 cm and group
      2 of patients with left atrium diameter >5 cm. The primary endpoint of the study
      was stable sinus rhythm 6 months postoperatively. At 6 months postoperatively,
      sinus rhythm was present in significantly more group 1 patients as compared with
      group 2 patients, i.e. 15 (75%) vs. 8 (40%), p=0.025. Multivariate analysis
      proved the size of the left atrium to be an independent predictor of the
      radiofrequency ablation outcome. Accordingly, the size of the left atrium was
      demonstrated to be an important predictor of the outcome of radiofrequency
      ablation for atrial fibrillation. A lower cut-off value of surgical reduction of
      the atria than previously reported should be considered in order to improve the
      radiofrequency ablation outcome.

PMID- 29590739
TI  - Gastrostomy Under Paravertebral Block in High-Risk Patients with Esophageal
      Cancer - Two Case Reports.
AB  - Here we present two cases of gastrostomy insertion via laparotomy in patients
      with malignant esophageal disease. Patients were ASA (American Society of
      Anesthesiologists) physical status III and IV. The patients presented as very
      high risk for general anesthesia, so we decided to use unilateral left sided
      paravertebral block (PVB) on four thoracic levels along with contralateral local
      infiltration at the gastrostomy insertion site. We present two cases, one of them
      a 57-year-old male ASA III patient scheduled for a gastrostomy procedure due to
      esophageal cancer with infiltration of the trachea. We also present a case of a
      59-year-old male patient, ASA IV status, scheduled for the same procedure due to
      advanced esophageal cancer with a fistula between the left main bronchus and the
      esophagus and metastases in the left lung. The paravertebral space was identified
      with the use of an 8 Hertz (Hz) linear ultrasound probe and a nerve stimulator.
      Paravertebral block was successfully used for insertion of a gastrostomy, thereby
      enabling adequate anesthesia and perioperative analgesia without hemodynamic or
      respiratory complications.

PMID- 29590740
TI  - Uniportal Video-Assisted Thoracic Surgery for Pulmonary Hamartoma: Case Report.
AB  - Pulmonary hamartoma is the most common benign tumor of the lung. It accounts for
      77% of all benign lung tumors but less than 1% of all lung tumors. Malignant
      alteration is -extremely rare. Surgical removal is therapy of choice. Uniportal
      video-assisted thoracic surgery is an easy-to-learn variant of video-assisted
      thoracic surgery. The approach is very similar to classic thoracotomy.
      Instruments for both classic and video-assisted thoracic surgery can be combined.
      A case is presented of a 44-year-old female patient with pulmonary hamartoma
      treated by uniportal video-assisted -thoracic surgery as a new method used for
      the first time at our department.

PMID- 29590741
TI  - Relapse of Pleomorphic Adenoma from Childhood to Adulthood: Case Report.
AB  - Pleomorphic adenoma is rarely seen in childhood. After detailed literature
      search, we did not come across a case of frequent relapse of this benign tumor
      from childhood to adulthood. The World Health Organization defines relapse of
      pleomorphic adenoma as a histologically benign tumor that can have local or
      distant metastasis. There is one hypothesis how benign tumor can metastasize.
      According to this hypothesis, probably during the first operative procedure the
      tissue around the tumor becomes permeable for tumor cells, which can lead to
      implantation of tumor cells into the surrounding tissue. In this case report, we
      present a case of a 30-year-old woman with pleomorphic adenoma of the
      submandibular gland, which relapsed three times. The patient was first operated
      on in 1993, at the age of 7 years. The first two relapses occurred in 1998 and
      2001, at the age of 12 and 15, respectively. The last relapse occurred in 2015,
      at the age of 29 years. All relapses were localized in the submandibular region
      on the right side of the neck, where the primary tumor had been operated on.

PMID- 29590742
TI  - Myasthenia Gravis Associated With Thymoma And Aplastic Anemia: Case Report.
AB  - Myasthenia gravis is associated in 10 to 15 percent of patients with thymic
      tumors, rarely with aplastic anemia. We report a 45-year-old male diagnosed with
      myasthenia gravis associated with thymoma. We started treatment with
      pyridostigmine. After thymectomy, the patient received 30 irradiation sessions.
      In the postoperative course, he had mild worsening of myasthenia gravis, which
      improved with prednisone. Five months later, he developed severe aplastic anemia.
      He was dependent on blood supplement. After allogeneic transplantation of bone
      marrow, he improved but later he -developed graft versus host disease. Myasthenia
      gravis was under good control with 480 mg of pyridostigmine per day.

PMID- 29590743
TI  - Intraoperative Spontaneous Rupture of Uterine Varicose Vein.

PMID- 29590744
TI  - The Clinical Efficacy of Silicone Stents for Endoscopic Dacryocystorhinostomy: A
      Meta-Analysis.
AB  - We evaluated the effect of silicone stent use during endoscopic
      dacryocystorhinostomy on postoperative morbidities in comparison with versus
      without a silicone stent. Two authors independently searched six databases
      (PubMed, Embase, Scopus, the Web of Science, the Cochrane library, and Google
      Scholar) from inception of article collection to July 2017. The analysis included
      prospective randomized studies that compared intraoperative silicone stent
      insertion (silicone group) with no application of a silicone stent (control
      group), in which the outcomes of interest were success rate (lacrimal passage
      patent check with syringing, symptom relief, or endoscopic confirmation of
      fluorescein dye from the opening of Hasner's valve) and morbidities (e.g.,
      postoperative bleeding, rhinostomy closure, granulation tissue, synechia, and
      eyelid problems) after certain follow-up periods (over 10 weeks). Nine studies
      involving a total of 587 participants were included. Functional success rates
      tended to be higher in the silicone group than in the control, but there was no
      statistically significant difference in success rates (odds ratio, 1.45; 95%
      confidence interval, 0.77 to 2.73). According to the surgical type such as
      mucosal removal and mucosal flap surgery, the results from types didn't
      demonstrate any significant effect, but the mucosal flap technique seemed to be
      more beneficial. Regarding postoperative morbidities, although the outcomes of
      the groups did not present any statistically significant difference, eyelid
      problems and postoperative bleeding tended to occur more frequently in the
      silicone group, but rhinostomy closure tended to occur more frequently in the
      control group. Success and morbidity rates showed no difference between the
      silicone stent group and control group in the meta-analysis. However, additional
      analyses revealed that the success rate of endonasal dacryocystorhinostomy using
      silicone intubation with mucosal flap has shown an improving trend, and
      morbidities such as granulation and synechia showed decreasing trends compared
      with the group without silicone intubation.

PMID- 29590745
TI  - High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex
      Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine
      Receptors in Hemi-Parkinsonian Rats.
AB  - Deep brain stimulation (DBS) is widely used to treat advanced Parkinson's disease
      (PD).Here, we investigated how DBS applied on the subthalamic nucleus (STN)
      influenced the neuralactivity in the motor cortex. Rats, which had the midbrain
      dopaminergic neurons partially depletedunilaterally, called the hemi-Parkinsonian
      rats, were used as a study model. c-Fos expression in theneurons was used as an
      indicator of neural activity. Application of high-frequency stimulation (HFS)upon
      the STN was used to mimic the DBS treatment. The motor cortices in the two
      hemispheres ofhemi-Parkinsonian rats were found to contain unequal densities of c
      Fos-positive (Fos+) cells, andSTN-HFS rectified this bilateral imbalance. In
      addition, STN-HFS led to the intense c-Fos expressionin a group of motor cortical
      neurons which exhibited biochemical and anatomical characteristicsresembling
      those of the pyramidal tract (PT) neurons sending efferent projections to the
      STN. Thenumber of PT neurons expressing high levels of c-Fos was significantly
      reduced by local applicationof the antagonists of non-N-methyl-D-aspartate (non
      NMDA) glutamate receptors, gammaaminobutyricacid A (GABAA) receptors and dopamine
      receptors in the upper layers of the motorcortex. The results indicate that the
      coincident activations of synapses and dopamine receptors inthe motor cortex
      during STN-HFS trigger the intense expression of c-Fos of the PT neurons.
      Theimplications of the results on the cellular mechanism underlying the
      therapeutic effects of STN-DBSon the movement disorders of PD are also discussed.

PMID- 29590746
TI  - Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal
      Cancer Harboring BRAF V600E Mutation.
AB  - BACKGROUND: BRAF mutation has been recognized as an important biomarker of
      colorectal cancer (CRC) for targeted therapy and prognosis prediction. However,
      sequencing for every CRC case is not cost-effective. An antibody specific for
      BRAF V600E mutant protein has been introduced, and we thus examined the utility
      of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC. METHODS:
      Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs
      between 2005 and 2015 were selected from the archives of Asan Medical Center.
      Tissue microarrays were constructed and stained with BRAF VE1 antibody. RESULTS:
      Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate
      cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild
      type cases also stained positive with BRAF VE1 antibody; four stained weakly and
      two stained moderately. Normal colonic crypts showed nonspecific weak staining,
      and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10
      BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and
      worse survival than BRAF wild-type patients. CONCLUSIONS: BRAF VE1
      immunohistochemistry showed high sensitivity and specificity, but occasional
      nonspecific staining in tumor cell nuclei and normal colonic crypts may limit
      their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful
      screening tool for BRAF V600E mutation in CRCs, provided that additional
      sequencing studies can be done to confirm the mutation in BRAF VE1 antibody
      positive cases.

PMID- 29590747
TI  - Collagenous Spherulosis Associated with Lobular Carcinoma In Situ of the Breast:
      Two Case Reports.

PMID- 29590748
TI  - Interfacial Mechanophore Activation Using Laser-Induced Stress Waves.
AB  - A new methodology is developed to activate and characterize mechanochemical
      transformations at a solid interface. Maleimide-anthracene mechanophores
      covalently anchored at a fused silica-polymer interface are activated using laser
      induced stress waves. Spallation-induced mechanophore activation is observed
      above a threshold activation stress of 149 MPa. The retro [4+2] cycloaddition
      reaction is confirmed by fluorescence microscopy, XPS, and ToF-SIMS measurements.
      Control experiments with specimens in which the mechanophore is not covalently
      attached to the polymer layer exhibit no activation. In contrast to activation in
      solution or bulk polymers, whereby a proportional increase in mechanophore
      activity is observed with applied stress, interfacial activation occurs
      collectively with spallation of the polymer film.

PMID- 29590749
TI  - Discovery of a Potent (4 R,5 S)-4-Fluoro-5-methylproline Sulfonamide Transient
      Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug
      Guided by Molecular Modeling.
AB  - Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel
      expressed in sensory neurons where it functions as an irritant sensor for a
      plethora of electrophilic compounds and is implicated in pain, itch, and
      respiratory disease. To study its function in various disease contexts, we sought
      to identify novel, potent, and selective small-molecule TRPA1 antagonists. Herein
      we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a
      novel and potent (4 R,5 S)-4-fluoro-5-methylproline sulfonamide series of
      inhibitors. Molecular modeling was utilized to derive low-energy three
      dimensional conformations to guide ligand design. This effort led to compound 20,
      which possessed a balanced combination of potency and metabolic stability but
      poor solubility that ultimately limited in vivo exposure. To improve solubility
      and in vivo exposure, we developed methylene phosphate prodrug 22, which
      demonstrated superior oral exposure and robust in vivo target engagement in a rat
      model of AITC-induced pain.

PMID- 29590750
TI  - Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic
      Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.
AB  - Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease
      produced by Trypanosoma brucei ( T. b.) species and a potential drug target for
      the treatment of human African trypanosomiasis (HAT). A library of hCatL
      inhibitors was screened, and macrocyclic lactams were identified as potent RD
      inhibitors ( Ki < 10 nM), preventing the cell-growth of Trypanosoma brucei
      rhodesiense (IC50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were
      established. Three cocrystal structures with RD revealed a noncovalent binding
      mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic
      acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was
      measured and the in vivo brain penetration in rats determined. When tested in
      vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for
      untreated controls) mean days of survival.

PMID- 29590751
TI  - 2 H-1,2,3-Triazole-Based Dipeptidyl Nitriles: Potent, Selective, and Trypanocidal
      Rhodesain Inhibitors by Structure-Based Design.
AB  - Macrocyclic inhibitors of rhodesain (RD), a parasitic cysteine protease and drug
      target for the treatment of human African trypanosomiasis, have shown low
      metabolic stability at the macrocyclic ether bridge. A series of acyclic
      dipeptidyl nitriles was developed using structure-based design (PDB ID: 6EX8 ).
      The selectivity against the closely related cysteine protease human cathepsin L
      (hCatL) was substantially improved, up to 507-fold. In the S2 pocket, 3,4
      dichlorophenylalanine residues provided high trypanocidal activities. In the S3
      pocket, aromatic residues provided enhanced selectivity against hCatL. RD
      inhibition ( Ki values) and in vitro cell-growth of Trypanosoma brucei
      rhodesiense (IC50 values) were measured in the nanomolar range. Triazole-based
      ligands, obtained by a safe, gram-scale flow production of ethyl 1 H-1,2,3
      triazole-4-carboxylate, showed excellent metabolic stability in human liver
      microsomes and in vivo half-lives of up to 1.53 h in mice. When orally
      administered to infected mice, parasitaemia was reduced but without complete
      removal of the parasites.

PMID- 29590752
TI  - Total Synthesis of Tiacumicin A. Total Synthesis, Relay Synthesis, and
      Degradation Studies of Fidaxomicin (Tiacumicin B, Lipiarmycin A3).
AB  - The commercial macrolide antibiotic fidaxomicin was synthesized in a highly
      convergent manner. Salient features of this synthesis include a beta-selective
      noviosylation, a beta-selective rhamnosylation, a ring-closing metathesis, a
      Suzuki coupling, and a vinylogous Mukaiyama aldol reaction. Careful choice of
      protecting groups and fine-tuning of the glycosylation reactions led to the first
      total synthesis of fidaxomicin. In addition, a relay synthesis of fidaxomicin was
      established, which gives access to a conveniently protected intermediate from the
      natural material for derivatization. The first total synthesis of a related
      congener, tiacumicin A, is presented.

PMID- 29590753
TI  - Detachment of Rough Colloids from Liquid-Liquid Interfaces.
AB  - Particle surface roughness and chemistry play a pivotal role in the design of new
      particle-based materials. Although the adsorption of rough particles has been
      studied in the literature, desorption of such particles remains poorly
      understood. In this work, we specifically focus on the detachment of rough and
      chemically modified raspberry-like microparticles from water/oil interfaces using
      colloidal-probe atomic force microscopy. We observe different contact-line
      dynamics occurring upon particle detachment (pinning vs sliding), depending on
      both the particle roughness and surface modification. In general, surface
      roughness leads to a reduction of the desorption force of hydrophobic particles
      into the oil and provides a multitude of pinning points that can be accessed by
      applying different loads. Our results hence suggest future strategies for
      stabilization and destabilization of Pickering emulsions and foams.

PMID- 29590754
TI  - Construction of ZnIn2S4-In2O3 Hierarchical Tubular Heterostructures for Efficient
      CO2 Photoreduction.
AB  - We demonstrate the rational design and construction of sandwich-like ZnIn2S4
      In2O3 hierarchical tubular heterostructures by growing ZnIn2S4 nanosheets on both
      inner and outer surfaces of In2O3 microtubes as photocatalysts for efficient CO2
      photoreduction. The unique design integrates In2O3 and ZnIn2S4 into hierarchical
      one-dimensional (1D) open architectures with double-heterojunction shells and
      ultrathin two-dimensional (2D) nanosheet subunits. This design accelerates the
      separation and transfer of photogenerated charges, offers large surface area for
      CO2 adsorption, and exposes abundant active sites for surface catalysis.
      Benefiting from the structural and compositional merits, the optimized ZnIn2S4
      In2O3 photocatalyst exhibits outstanding performance for reductive CO2
      deoxygenation with considerable CO generation rate (3075 MUmol h-1 g-1) and high
      stability.

PMID- 29590755
TI  - Bioinspired Star-Shaped Poly(l-lysine) Polypeptides: Efficient Polymeric
      Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells.
AB  - The field of tissue engineering is increasingly recognizing that gene therapy can
      be employed for modulating in vivo cellular response thereby guiding tissue
      regeneration. However, the field lacks a versatile and biocompatible gene
      delivery platform capable of efficiently delivering transgenes to mesenchymal
      stem cells (MSCs), a cell type often refractory to transfection. Herein, we
      describe the extensive and systematic exploration of three architectural
      variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying
      number and length of poly(l-lysine) arms as potential nonviral gene delivery
      vectors for MSCs. We demonstrate that star-PLL vectors are capable of self
      assembling with pDNA to form stable, cationic nanomedicines. Utilizing high
      content screening, live cell imaging, and mechanistic uptake studies we confirm
      the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which
      likely proceeds via a clathrin-independent mechanism. We identify a star-PLL
      composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a
      particularly efficient vector that is capable of delivering both reporter genes
      and the therapeutic transgenes bone morphogenetic protein-2 and vascular
      endothelial growth factor to MSCs. This composition facilitated a 1000-fold
      increase in transgene expression in MSCs compared to its linear analogue, linear
      poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to
      the widely used vector polyethylenimine using a lower pDNA dose with
      significantly less cytotoxicity. Overall, this study illustrates the ability of
      the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to
      MSCs thereby functioning as an innovative nanomedicine platform for tissue
      engineering applications.

PMID- 29590756
TI  - Improved Outcomes With Integrated Intensivist Consultation for Cardiac Surgery
      Patients.
AB  - This study examined the impact of integrated intensivist consultation in the
      immediate postoperative period on outcomes for cardiac surgery patients. A
      retrospective cohort study was conducted in 1711 adult cardiac surgery patients
      from a single quaternary care center in Minnesota. Outcomes were compared across
      2 consecutive 2-year time periods reflecting an elective intensivist model (n =
      801) and an integrated intensivist model (n = 910). Patients under the 2 models
      were comparable with respect to demographics, comorbidities, procedure types, and
      Society for Thoracic Surgery predicted risk of mortality score; however, patients
      in the earlier cohort were slightly older and more likely to have chronic kidney
      disease ( P = .003). Integrated intensivist involvement was associated with
      reduced postoperative ventilator time, length of stay (LOS), stroke,
      encephalopathy, and reoperations for bleeding (all P < .01) but was not
      associated with mortality. Intensivist integration into the postoperative care of
      cardiac surgery patients may reduce ventilator time, LOS, and complications but
      may not improve survival.

PMID- 29590757
TI  - Hope Tree: An Interactive Art Installation to Facilitate the Expression of Hope
      in a Hospice Setting.
AB  - BACKGROUND: Individuals confronting a terminal illness can experience intense
      psychological distress. Previous research has shown that hope can enhance one's
      ability to acknowledge, accept, and fight a terminal illness. Patients can
      continue to have hope or be hopeful, even in the face of a terminal illness. Can
      participation in a creative writing practice improve the expression of hope in a
      hospice setting? METHODS: In this program evaluation, each expressed hope placed
      on the "Hope Tree" was independently coded by all research team members utilizing
      inductive content analysis. Overall themes were derived using a constant
      comparative approach and arranged into overarching themes based on consensus.
      RESULTS: Eight major themes emerged from the data: "Peace," "Dreams," "Total well
      being," "Acknowledgment of loss," "Relationships," "Hospice care,"
      "Spirituality," and "Dichotomies." CONCLUSION: The Hope Tree is a creative art
      project that can be used within a hospice environment to promote hope among
      family members and the health-care professionals who care for patients.

PMID- 29591320
TI  - Lumbrical muscle tear: clinical presentation, imaging findings and outcome.
AB  - : The incidence of lumbrical muscle tear is increasing due to the popularity of
      climbing sport. We reviewed data from 60 consecutive patients with a positive
      lumbrical stress test, including clinical examination, ultrasound and clinical
      outcomes in all patients, and magnetic resonance imaging in 12 patients. Fifty
      seven patients were climbers. Lumbrical muscle tears were graded according to the
      severity of clinical and imaging findings as Grade I-III injuries. Eighteen
      patients had Grade I injuries (microtrauma), 32 had Grade II injuries (muscle
      fibre disruption) and 10 had Grade III injuries (musculotendinous disruption).
      The treatment consisted of adapted functional therapy. All patients completely
      recovered and were able to return to climbing. The healing period in Grade III
      injuries was significantly longer than in the patients with Grade I or II
      injuries ( p < 0.001). We recommend evaluation of specific clinical and imaging
      findings to grade the injuries and to determine suitable therapy. LEVEL OF
      EVIDENCE: IV.

PMID- 29591321
TI  - Dorsal fracture-subluxation of the distal interphalangeal joint.

PMID- 29591322
TI  - Treatment of dorsal fracture-dislocations of the proximal interphalangeal joint
      using the shotgun approach.
AB  - : This study assessed the outcome of open reduction and internal fixation of
      proximal interphalangeal joint fracture-dislocations through a shotgun approach,
      while keeping hemi-hamate arthroplasty as a back-up plan. After using the shotgun
      approach, fixation was carried out when the anterior fragment was large enough to
      accept two 1.5 mm screws. Sixty-three fracture-dislocations were treated in 61
      patients, of whom 30 underwent internal fixation. Twenty-one of these were
      assessed in the final study. At a mean follow-up of 29 months, the mean range of
      joint motion was 80 degrees  and 102 degrees  for the injured and contralateral
      hand, respectively. The mean pinch and grip strengths of injured hand were 82%
      and 83% of contralateral hand, respectively. The mean disabilities of the arm,
      shoulder and hand score was 5.5. The mean visual analogue pain score was 1.6.
      Surgery through the versatile shotgun approach allows excellent intra-operative
      assessment and acceptable outcomes. LEVEL OF EVIDENCE: IV.

PMID- 29591369
TI  - Pharmacists' Impact on Secondary Stroke Prevention.
AB  - BACKGROUND: Patients admitted to our institution with a cerebrovascular accident
      (stroke) or transient ischemic attack (TIA) are referred to the pharmacist-run
      stroke prevention clinic (SPC) for medication and risk factor management.
      OBJECTIVE: The objective was to determine if patients receiving care from the SPC
      have better outcomes than patients who received usual care. METHODS: This was a
      retrospective chart review of patients referred to the SPC. At the time of
      stroke/TIA, before initial visit, and after last SPC visit, risk factor data was
      collected. Hospital readmissions were reviewed for secondary stroke/TIA,
      myocardial infarction (MI), and new or incidental peripheral artery disease
      (PAD). For patients that did not attend SPC visits, data was used as a control.
      RESULTS: Patients referred to the SPC from October 2012 to December 2014 were
      reviewed. 455 records were reviewed. The primary composite end point of
      readmission for stroke/TIA, myocardial infarction, and new or incidental PAD was
      statistically significantly lower in the SPC group than the control group ( P =
      .013). All surrogate markers, including blood pressure, Low Density Lipoprotein,
      Hemoglobin A1c, and smoking status, improved in the SPC group. CONCLUSION:
      Pharmacists can play a role in reducing risk factors for secondary stroke/TIA and
      prevent future hospital admissions.

PMID- 29591488
TI  - Prediction of microRNA-binding residues in protein using a Laplacian support
      vector machine based on sequence information.
AB  - The identification of microRNA (miRNA)-binding protein residues significantly
      impacts several research areas, including gene regulation and expression. We
      propose a method, PmiRBR, which combines a novel hybrid feature with the
      Laplacian support vector machine (LapSVM) algorithm to predict miRNA-binding
      residues in protein sequences. The hybrid feature is constituted by secondary
      structure, conservation scores, and a novel feature, which includes evolutionary
      information combined with the physicochemical properties of amino acids.
      Performance comparisons of the various features indicate that our novel feature
      contributes the most to prediction improvement. Our results demonstrate that
      PmiRBR can achieve 85.96% overall accuracy, with 43.89% sensitivity and 90.56%
      specificity. PmiRBR significantly outperforms other approaches at miRNA-binding
      residue prediction.

PMID- 29591533
TI  - Peritoneal dialysis catheter insertion surgery and management.
AB  - Peritoneal access surgery is the first step to achieve successful peritoneal
      dialysis. It is important to perform easy, safe, and less invasive surgery of
      peritoneal dialysis catheter insertion. Secure peritoneal dialysis catheter
      insertion will lead to less infection, that is, exit site, tunnel infection, and
      peritonitis, which sometimes result in peritoneal dialysis discontinuation. To
      avoid these undesirable results, we should perform good and proper peritoneal
      dialysis insertion surgery. In this article, we describe peritoneal dialysis
      catheter insertion surgery and its management.

PMID- 29591534
TI  - Physical activity volume in relation to risk of atrial fibrillation. A non-linear
      meta-regression analysis.
AB  - Background Light physical activity is known to reduce atrial fibrillation risk,
      whereas moderate to vigorous physical activity may result in an increased risk.
      However, the question of what volume of physical activity can be considered
      beneficial remains poorly understood. The scope of the present work was to
      examine the relation between physical activity volume and atrial fibrillation
      risk. Design A comprehensive systematic review was performed following the PRISMA
      guidelines. Methods A non-linear meta-regression considering the amount of energy
      spent in physical activity was carried out. The first derivative of the non
      linear relation between physical activity and atrial fibrillation risk was
      evaluated to determine the volume of physical activity that carried the minimum
      atrial fibrillation risk. Results The dose-response analysis of the relation
      between physical activity and atrial fibrillation risk showed that physical
      activity at volumes of 5-20 metabolic equivalents per week (MET-h/week) was
      associated with significant reduction in atrial fibrillation risk (relative risk
      for 19 MET-h/week = 0.92 (0.87, 0.98). By comparison, physical activity volumes
      exceeding 20 MET-h/week were unrelated to atrial fibrillation risk (relative risk
      for 21 MET-h/week = 0.95 (0.88, 1.02). Conclusion These data show a J-shaped
      relation between physical activity volume and atrial fibrillation risk. Physical
      activity at volumes of up to 20 MET-h/week is associated with reduced atrial
      fibrillation risk, whereas volumes exceeding 20 MET-h/week show no relation with
      risk.

PMID- 29591535
TI  - Reply to the letter 'Is a rapid increase in nitrogen oxides really associated
      with an acute myocardial infarction?'

PMID- 29591536
TI  - Sequence typing of human adenoviruses isolated from Polish patients subjected to
      allogeneic hematopoietic stem cell transplantation - a single center experience.
AB  - PURPOSE: Human adenoviruses (HAdV) from species A, B and C are commonly
      recognized as pathogens causing severe morbidity and mortality in hematopoietic
      stem cell transplant (HSCT) recipients. The purpose of the present study was to
      determine HAdV types responsible for viremia in HSCT recipients at a large
      tertiary hospital in Poland. METHODS: Analysis of partial nucleotide sequences of
      HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40
      HSCT recipients. RESULTS: We identified six different HAdV serotypes belonging to
      species B, C and E. We demonstrated high variability in sequences of detected
      HAdV types, and patients infected with the same HAdV types were not hospitalized
      at the same time, which suggests the low possibility of cross-infection. In
      almost all patients, anti-HAdV antibodies in IgG class were detected, which
      indicates a history of HAdV infection in the past. Clinical symptoms accompanying
      HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen
      detected. There were no cases with high-level HAdV viremia and severe systemic or
      organ infections. Graft-versus-host disease (GvHD) was present in patients
      infected with species B and C, but grade II of GvHD was observed only in patients
      infected with HAdV-B. CONCLUSIONS: The predominance of HAdV-C and common presence
      of anti-HAdV antibodies in IgG class may strongly suggest that most infections in
      the present study were reactivations of HAdV persisting into the patient's mucosa
      associated lymphoid tissues. Variability of HAdV sequences suggests that cross
      infections between patients were very rare. ABBREVIATIONS: GvHD: graft-versus
      host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell
      transplantation.

PMID- 29591537
TI  - Is Ego Depletion Real? An Analysis of Arguments.
AB  - An influential line of research suggests that initial bouts of self-control
      increase the susceptibility to self-control failure (ego depletion effect).
      Despite seemingly abundant evidence, some researchers have suggested that
      evidence for ego depletion was the sole result of publication bias and p-hacking,
      with the true effect being indistinguishable from zero. Here, we examine (a)
      whether the evidence brought forward against ego depletion will convince a
      proponent that ego depletion does not exist and (b) whether arguments that could
      be brought forward in defense of ego depletion will convince a skeptic that ego
      depletion does exist. We conclude that despite several hundred published studies,
      the available evidence is inconclusive. Both additional empirical and theoretical
      works are needed to make a compelling case for either side of the debate. We
      discuss necessary steps for future work toward this aim.

PMID- 29591538
TI  - Quality Measurement Recommendations Relevant to Clinical Guidelines in Germany
      and the United Kingdom: (What) Can We Learn From Each Other?
AB  - We conducted a systematic review of clinical guidelines (CGs) to examine the
      methodological approaches of quality indicator derivation in CGs, the frequency
      of quality indicators to check CG recommendations in routine care, and
      clinimetric properties of quality indicators. We analyzed the publicly available
      CG databases of the Association of the Scientific Medical Societies in Germany
      (AWMF) and National Institute for Health and Care Excellence (NICE). Data on the
      methodology of subsequent quality indicator derivation, the content and
      definition of recommended quality indicators, and clinimetric properties of
      measurement instruments were extracted. In Germany, no explicit methodological
      guidance exists, but 3 different approaches are used. For NICE, a general
      approach is used for the derivation of quality indicators out of quality
      standards. Quality indicators were defined in 34 out of 87 CGs (39%) in Germany
      and for 58 out of 133 (43%) NICE CGs. Statements regarding measurement properties
      of instruments for quality indicator assessment were missing in German and NICE
      documents. Thirteen pairs of CGs (32%) have associated quality indicators. Thirty
      four quality indicators refer to the same aspect of the quality of care, which
      corresponds to 27% of the German and 7% of NICE quality indicators. The
      development of a standardized and internationally accepted methodology for the
      derivation of quality indicators relevant to CGs is needed to measure and compare
      quality of care in health care systems.

PMID- 29591539
TI  - Reducing High-Users' Visits to the Emergency Department by a Primary Care
      Intervention for the Uninsured: A Retrospective Study.
AB  - Reducing avoidable emergency department (ED) visits is an important health system
      goal. This is a retrospective cohort study of the impact of a primary care
      intervention including an in-hospital, free, adult clinic for poor uninsured
      patients on ED visit rates and emergency severity at a nonprofit hospital. We
      studied adult ED visits during August 16, 2009-August 15, 2011 (preintervention)
      and August 16, 2011-August 15, 2014 (postintervention). We compared pre- versus
      post-mean annual visit rates and discharge emergency severity index (ESI; triage
      and resource use-based, calculated Agency for Healthcare Research and Quality
      categories) among high-users (>=3 ED visits in 12 months) and occasional users.
      Annual adult ED visit volumes were 16 372 preintervention (47.5% by high-users),
      versus 18 496 postintervention. High-users' mean annual visit rates were 5.43
      (top quartile) and 0.94 (bottom quartile) preintervention, versus 3.21 and 1.11,
      respectively, for returning high-users, postintervention (all P < .001).
      Postintervention, the visit rates of new high-users were lower (lowest and top
      quartile rates, 0.6 and 3.23) than preintervention high-users' rates in the
      preintervention period. Visit rates of the top quartile of occasional users also
      declined. Subgroup analysis of medically uninsured high-users showed similar
      results. Upon classifying preintervention high-users by emergency severity,
      postintervention mean ESI increased 24.5% among the lowest ESI quartile, and
      decreased 12.2% among the top quartile. Pre- and post-intervention sample
      demographics and comorbidities were similar. The observed reductions in overall
      ED visit rates, particularly low-severity visits; highest reductions observed
      among high-users and the top quartile of occasional users; and the pattern of
      changes in emergency severity support a positive impact of the primary care
      intervention.

PMID- 29591540
TI  - Comprehensive Support for Family Caregivers of Post-9/11 Veterans Increases
      Veteran Utilization of Long-term Services and Supports: A Propensity Score
      Analysis.
AB  - Family caregivers are an important component of the long-term services and
      supports (LTSS) system. However, caregiving may have negative consequences for
      caregiver physical and emotional health. Connecting caregivers to formal short
      term home- and community-based services (HCBS), through information resources and
      referrals, might alleviate family caregiver burden and delay nursing home entry
      for the patient. The aim of this study was to evaluate the early impact of the
      Program of Comprehensive Assistance for Family Caregivers (PCAFC) (established by
      P.L. 111-163 for family caregivers of seriously injured post-9/11 Veterans) on
      Veteran use of LTSS. A two-cohort pre-post design with a nonequivalent comparison
      group (treated n = 15 650; comparison n = 8339) was used to (1) examine the
      association between caregiver enrollment in PCAFC and any VA-purchased or VA
      provided LTSS use among Veterans and (2) describe program-related trends in HCBS
      and institutional LTSS use. The comparison group was an inverse-propensity-score
      weighted sample of Veterans whose caregivers applied for, but were not accepted
      into, the program. From baseline through 24 months post application, use of any
      LTSS ranged from 13.1% to 17.8% for Veterans whose caregivers were enrolled in
      PCAFC versus from 3.8% to 5.3% for Veterans in the comparison group.
      Participation in PCAFC was associated with a statistically significant increased
      use of any LTSS from 1 to 24 months post application (over time odds ratios
      ranged from 2.71 [95% confidence interval: 2.31-3.17] to 4.86 [3.93-6.02]).
      Support for family caregivers may enhance utilization of LTSS for Veterans with
      physical, emotional, and/or cognitive conditions.

PMID- 29591587
TI  - Perceived Calling and Work Engagement Among Nurses.
AB  - The purpose of this study was to explore the relationship of perceived calling
      and work engagement in nursing over and above major work environment factors. In
      all, 351 nurses from various health care institutions completed the survey. Data
      were collected about the most demanding aspects of nursing, major job resources,
      the degree to which nursing is perceived as a meaningful calling, work
      engagement, and main demographic information. Hierarchical linear regression was
      applied to assess the relation between perceived calling and work engagement,
      while controlling for demographic and work environment factors, and perceived
      calling was significantly related to two out of three components of nurses' work
      engagement. The highest association was found with dedication component, and
      vigor component was related insignificantly. Results have shown that perceived
      calling might motivate nurses to engage in their work even in burdensome
      environment, although possible implications for the occupational well-being of
      nurses themselves remains unclear.

PMID- 29591721
TI  - "Twig-like" cerebral vessels are not pathognomonic for ACTA A2 mutations: A case
      report.
AB  - ACTA2 mutations are recently described genetically defined abnormalities of blood
      vessels in various organs of the body with specific abnormalities in cerebral
      vessels in the form of straightening of all cerebral arteries ("twig-like"
      pattern), stenosis/occlusions, proximal dilatation, and absent "moyamoya" type of
      collaterals. We describe a one-and-a half year-old girl child who presented with
      mild motor developmental delay and on neuroimaging showed septo-preoptic
      holoprosencephaly, diffuse radial polymicrogyria, and pontine hypoplasia along
      with magnetic resonance angiographic features suggestive of ACTA2 mutation type
      of cerebral vessels. However, genetic studies revealed no evidence of ACTA2
      mutation, indicating that the "twig-like" pattern may not only be a pathognomonic
      feature of ACTA2 mutations.

PMID- 29591722
TI  - High-throughput terrestrial biodiversity assessments: mitochondrial
      metabarcoding, metagenomics or metatranscriptomics?
AB  - Consensus on the optimal high-throughput sequencing (HTS) approach to examine
      biodiversity in mixed terrestrial arthropod samples has not been reached.
      Metatranscriptomics could increase the proportion of taxonomically informative
      mitochondrial reads in HTS outputs but has not been investigated for terrestrial
      arthropod samples. We compared the efficiency of 16S rRNA metabarcoding,
      metagenomics and metatranscriptomics for detecting species in a mixed terrestrial
      arthropod sample (pooled DNA/RNA from 38 taxa). 16S rRNA metabarcoding and
      nuclear rRNA-depleted metatranscriptomics had the highest detection rate with 97%
      of input species detected. Based on cytochrome c oxidase I, metagenomics had the
      highest detection rate with 82% of input species detected, but
      metatranscriptomics produced a larger proportion of reads matching (Sanger)
      reference sequences. Metatranscriptomics with nuclear rRNA depletion may offer
      advantages over metabarcoding through reducing the number of spurious operational
      taxonomic units while retaining high detection rates, and offers natural
      enrichment of mitochondrial sequences which may enable increased species
      detection rates compared with metagenomics.

PMID- 29591635
TI  - Are cannabis-using and non-using patients different groups? Towards understanding
      the neurobiology of cannabis use in psychotic disorders.
AB  - A substantial body of credible evidence has accumulated that suggest that
      cannabis use is an important potentially preventable risk factor for the
      development of psychotic illness and its worse prognosis following the onset of
      psychosis. Here we summarize the relevant evidence to argue that the time has
      come to investigate the neurobiological effects of cannabis in patients with
      psychotic disorders. In the first section we summarize evidence from longitudinal
      studies that controlled for a range of potential confounders of the association
      of cannabis use with increased risk of developing psychotic disorders, increased
      risk of hospitalization, frequent and longer hospital stays, and failure of
      treatment with medications for psychosis in those with established illness.
      Although some evidence has emerged that cannabis-using and non-using patients
      with psychotic disorders may have distinct patterns of neurocognitive and
      neurodevelopmental impairments, the biological underpinnings of the effects of
      cannabis remain to be fully elucidated. In the second and third sections we
      undertake a systematic review of 70 studies, including over 3000 patients with
      psychotic disorders or at increased risk of psychotic disorder, in order to
      delineate potential neurobiological and neurochemical mechanisms that may
      underlie the effects of cannabis in psychotic disorders and suggest avenues for
      future research.

PMID- 29591723
TI  - Improvement in the proinsulin/C-peptide ratio during treatment with ipragliflozin
      in Japanese patients with type 2 diabetes mellitus.

PMID- 29591724
TI  - Two-Year Outcomes of the Nellix EndoVascular Aneurysm Sealing System for
      Treatment of Abdominal Aortic Aneurysms.
AB  - PURPOSE: To analyze the 2-year outcomes of endovascular aneurysm sealing (EVAS)
      according to 2 versions of the instructions for use (IFU). METHODS: A
      retrospective study was conducted involving 355 consecutive patients treated with
      the first-generation EVAS device from April 2013 to December 31, 2015, at 3 high
      volume centers. Out of 355 patients treated with EVAS, 264 were elective
      asymptomatic infrarenal EVAS procedures suitable for analysis. In this cohort,
      168 (63.3%) patients were treated within the IFU 2013 criteria; of these 48
      (18.2%) were in compliance with the revised IFU 2016 version. RESULTS: Overall
      technical success was 98.2% (165/168) in the IFU 2013 group and 97.9% (47/48) in
      the IFU 2016 subgroup (p=0.428). The 2-year freedom from reintervention estimates
      were 89.7% (IFU 2013) and 95.7% (IFU 2016), with significantly more
      reinterventions in the first 45 cases (p=0.005). The stenosis/occlusion estimates
      were 6.5% (IFU 2013) and 4.2% (IFU 2016; p=0.705). Nine (5.4%) endoleaks (8 type
      Ia and 1 type Ib) were observed within the IFU 2013 cohort; 3 (2.1%) were in the
      IFU 2016 subgroup (p=0.583). Migration >=10 mm or >=5 mm requiring intervention
      was reported in 12 (7.1%) patients in the IFU 2013 cohort but none within the IFU
      2016 subgroup. Ten (6.0%) patients demonstrated aneurysm growth in the IFU 2013
      cohort, of which 2 (4.2%) were in the IFU 2016 subgroup. Overall survival and
      freedom from aneurysm-related death estimates at 2 years were 90.9% and 97.6% in
      the IFU 2013 cohort (IFU 2016: 95.5% and 100.0%). The prevalence of complications
      seemed lower within IFU 2016 without significant differences. CONCLUSION: This
      study shows acceptable 2-year results of EVAS used within the IFU, without
      significant differences between the 2 IFU versions, though longer follow-up is
      indicated. The refined IFU significantly reduced the applicability of the
      technique.

PMID- 29591838
TI  - Getting comfortable with "comfort feeding": An exploration of legal and ethical
      aspects of the Australian speech-language pathologist's role in palliative
      dysphagia care.
AB  - PURPOSE: With an ageing population, speech-language pathologists (SLPs) can
      expect to encounter legal and ethical challenges associated with palliative and
      end-of-life care more frequently. An awareness of the medico-legal and ethical
      framework for palliative dysphagia management will better equip SLPs to work
      effectively in this area. METHOD: This narrative review examines a range of
      legislation, legal, ethical and SLP literature that is currently available to
      orient SLPs to legal and ethical palliative dysphagia management in the
      Australian context. RESULT: Relevant legal and ethical considerations in
      palliative and end-of-life care are described. CONCLUSION: SLPs have a role in
      palliative dysphagia management, however, this can involve unique legal and
      ethical challenges. The legal position on provision and cessation of nutrition
      and hydration differs between Australian States and Territories. Decisions by the
      courts have established a body of relevant case law. This article introduces SLPs
      to some of the important considerations for legal and ethical palliative care,
      but is not intended to be directive. SLPs are encouraged to explore their local
      options for ethical and medico-legal guidance. It is hoped that increasing SLPs
      awareness of many of the concepts discussed in this article enhances the
      provision of high-quality patient-centred care.

PMID- 29591780
TI  - A comparison of the effects of carbon dioxide and medical air for abdominal
      insufflation on respiratory parameters in xylazine-sedated sheep undergoing
      laparoscopic artificial insemination.
AB  - AIMS: To determine if abdominal insufflation with medical air will improve
      oxygenation and ventilation parameters when compared to insufflation with CO2 in
      xylazine-sedated sheep undergoing laparoscopic artificial insemination (AI).
      METHODS: Forty-seven sheep underwent oestrus synchronisation and were fasted for
      24 hours prior to laparoscopic AI. Each animal was randomised to receive either
      CO2 or medical air for abdominal insufflation. An auricular arterial catheter was
      placed and utilised for serial blood sampling. Respiratory rates (RR) and
      arterial blood samples were collected at baseline, after xylazine (0.1 mg/kg I/V)
      sedation, 2 minutes after Trendelenburg positioning, 5 minutes after abdominal
      insufflation, and 10 minutes after being returned to a standing position. Blood
      samples were collected in heparinised syringes, stored on ice, and analysed for
      arterial pH, partial pressure of arterial O2 (PaO2), and CO2 (PaCO2). The number
      of ewes conceiving to AI was also determined. RESULTS: Repeated measures ANOVA
      demonstrated temporal effects on RR, PaO2, PaCO2 and arterial pH during the
      laparoscopic AI procedure (p<0.001), but no difference between insufflation
      groups (p>0.01). No sheep experienced hypercapnia (PaCO2>50 mmHg) or acidaemia
      (pH<7.35). Hypoxaemia (PaO2<70 mmHg) was diagnosed during the procedure in 14/22
      (64%) ewes in the CO2 group compared with 8/23 (35%) ewes in the medical air
      group (p=0.053). Overall, 15/20 (75%) ewes in the CO2 group conceived to AI
      compared with 16/22 (72.7%) in the medical air group (p=0.867). CONCLUSIONS AND
      CLINICAL RELEVANCE: There were no statistical or clinical differences in RR,
      PaO2, PaCO2, pH, or conception to AI when comparing the effects of CO2 and
      medical air as abdominal insufflation gases. None of the sheep experienced
      hypercapnia or acidaemic, yet 42% (19/45) of sheep developed clinical hypoxaemia,
      with a higher percentage of ewes in the CO2 group developing hypoxaemia than in
      the medical air group. Based on the overall analysis, medical air could be
      utilised as a comparable alternative for abdominal insufflation during
      laparoscopic AI procedures.

PMID- 29591886
TI  - Investigation of the genotoxic and cytotoxic effects of widely used neonicotinoid
      insecticides in HepG2 and SH-SY5Y cells.
AB  - Neonicotinoids are a relatively new type of insecticide to control a variety of
      pests. Although they are generally considered to be safe, they can lead to
      harmful effects on human and environmental health. We aimed to investigate
      possible effects of common neonicotinoid insecticides (acetamiprid, clothianidin,
      imidacloprid, thiacloprid, and thiamethoxam) on cytotoxicity and DNA damage in
      human neuroblastoma (SH-SY5Y) and human hepatocellular carcinoma (HepG2) cells.
      Our results indicated that 50% of inhibitory concentration values of
      neonicotinoids are in the range of 0.96 to >4 mM in SH-SY5Y cells and 0.53 to >4
      mM in HepG2 cells by the methyl tetrazolium and neutral red uptake tests after 24
      and 48 h exposure. We observed significant DNA damage at 500 uM of five
      neonicotinoids in SHSY-5Y cells, while only imidacloprid, thiametoxam, and
      thiacloprid showed some alterations in HepG2 cells after 24 h exposure using the
      alkaline comet assay. In conclusion, neonicotinoid insecticides may induce
      cytotoxicity and DNA damage in cell cultures; therefore, further studies are
      needed to better understand the toxicity of neonicotinoids.

PMID- 29591887
TI  - Pathology of cigarettes on the reproductive system and ameliorative effects of
      alpha lipoic acid: A rat model study.
AB  - Cigarette smoking (CS) has some detrimental effects that occur via oxidative
      stress (OS). The aim of this work was to demonstrate the pathological and
      immunohistochemical effects of CS and the protective effects of a strong
      antioxidant alpha lipoic acid (ALA) on CS-induced genital system changes in a rat
      model. Twenty-eight female rats were randomly allocated to three groups as
      control, CS-exposed, and CS-exposed and ALA-treated. Reproductive tract organs
      were collected for biochemical and pathological examinations. In the CS group, OS
      markers increased in the tissues of both the ovary and fallopian tubes. Decreased
      follicle numbers in the ovary, marked cilial loss in the fallopian tubes, and
      pathologic changes in the uterus were observed in the CS group. Positive
      calcitonin gene-related peptide (CGRP), caspase 3alpha, hypoxia-inducible factor
      1alpha (HIF-1alpha), tumor necrosis factor-alpha (TNF-alpha) immunoreactions were
      observed in uterine tissues and HIF-1alpha immunoreactions in tubal and uterine
      epithelial cells of the CS group. ALA reversed all these findings effectively. CS
      has negative effects on the female reproductive system via HIF-1alpha in tuba
      uterina and HIF-1alpha, HIF-2alpha, TNF-alpha, caspase 3, and CGRP in the uterus,
      and ALA could protect against the negative effects of CS on the female
      reproductive system.

PMID- 29591888
TI  - Effects of T-2 and Fumonisin B1 combined treatment on in vitro mouse embryo
      development and blastocyst quality.
AB  - In the temperate region, most common mycotoxins are members of fusariotoxins. It
      often happens that food and forage are contaminated with two or more
      fusariotoxins at the same time. Effects of co-contamination are poorly
      documented, especially in the field of reproduction. The aim of our study was to
      assess the combined effect of the two common fusariotoxins, T-2 toxin (T-2) and
      Fumonisin B1 on early mouse embryo development in vitro. Embryo culture media
      contained either (1) 0.5 ng/ml T-2; 1, 2, or 10 ng/ml FB1 (group A, B, and C,
      respectively); or (2) 0.5 ng/ml T-2 and 1, 2, or 10 ng/ml FB1 (group TA, TB, and
      TC, respectively). Developmental rate, blastocoel expansion, cell number, and
      micronucleus rate were measured following 96 h culture. Although the
      developmental rate was similar to the control group (86.43% vs. 83.33, 78.79,
      85.98, and 86.67%, respectively) in the case of single toxin treatments, the
      combined treatments induced significant decreases (14.5, 33.6, and 22.8% in TA,
      TB, and TC, respectively). The proportion of late blastocysts was lower in all
      treatments compared to control (83.6% vs. 0-83.6%). Combined treatment resulted
      in a significantly lower proportion of late blastocysts (25% in TA and 0% in TB
      and TC). Cell numbers decreased in all toxin-treated groups with a higher rate
      after combined treatments. No differences were detected in the micronucleus rate
      in the single or combined treatments compared to control. Our study shows that T
      2 and FB1 toxins do not necessarily decrease the developmental rate, but co
      contamination results in a significantly lower blastocyst rate and disturbs the
      blastocoel expansion as well. One possible explanation of this observation could
      be that the presence of two mycotoxins in the culture media intensifies their
      negative effects. All toxin treatments decreased the cell number in the
      blastocysts and this negative effect was more expressed after combined treatment.

PMID- 29591889
TI  - Impact of chromium and boron compounds on the reproductive function in rats.
AB  - The purpose of this research is to study the process of mutagenesis and the
      reproductive function in male rats under separate and combined exposure to
      chromium and boron compounds. The experiment was conducted on two groups of
      animals. The first group was used to assess the ability of potassium dichromate
      and boric acid to induce mutation in germ and somatic cells under isolated and
      combined administration with the use of the dominant lethal mutations test and
      the micronuclei test in the polychromatophilic erythrocytes of the bone marrow.
      The second group was used to test the combined and separate effect of the
      compounds under consideration on the reproductive function of male rats during
      the spermatogenesis cycle. When used in specific doses, boron compounds are a
      promising means of preventing and correcting chromium-induced effects in chromium
      production facility workers and people who live in ecologically adverse regions.

PMID- 29591890
TI  - Cadmium telluride quantum dots induce apoptosis in human breast cancer cell
      lines.
AB  - INTRODUCTION: Semiconductor quantum dots (QDs), especially those containing
      cadmium, have undergone marked improvements and are now widely used nanomaterials
      in applicable biological fields. However, great concerns exist regarding their
      toxicity in biomedical applications. Because of the lack of sufficient data
      regarding the toxicity mechanism of QDs, this study aimed to evaluate the
      cytotoxicity of three types of QDs: CdTe QDs, high yield CdTe QDs, and CdTe/CdS
      core/shell QDs on two human breast cancer cell lines MDA-MB468 and MCF-7.
      METHODS: The breast cancer cells were treated with different concentrations of
      QDs, and cell viability was evaluated via MTT assay. Hoechst staining was applied
      for observation of morphological changes due to apoptosis. Apoptotic DNA
      fragmentation was visualized by the agarose gel electrophoresis assay. Flow
      cytometric annexin V/propidium iodide (PI) measurement was used for apoptosis
      detection. RESULTS: A significant decrease in cell viability was observed after
      QDs treatment ( p < 0.05). Apoptotic bodies and chromatin condensation was
      observed by Hoechst staining. DNA fragmentation assay demonstrated a DNA ladder
      profile in the exposed cells and also annexin V/PI flow cytometry confirmed
      apoptosis in a dose-dependent manner. CONCLUSION: Our results revealed that CdTe,
      high yield CdTe, and CdTe/CdS core/shell QDs induce apoptosis in breast cancer
      cell lines in a dose-dependent manner. This study would help realizing the
      underlying cytotoxicity mechanism, at least partly, of CdTe QDs and may provide
      information for the development of nanotoxicology and safe use of biological
      applications of QDs.

PMID- 29591914
TI  - The Bethesda System for Reporting Thyroid Cytopathology Explained for
      Practitioners: Frequently Asked Questions.
AB  - BACKGROUND: The recent update of The Bethesda System for Reporting Thyroid
      Cytology (TBSRTC) is a very important development in the evaluation of thyroid
      nodules. Clinical experience and scientific literature both show that
      practitioners performing thyroid fine-needle aspiration are accustomed to basing
      the clinical management of patients on reports using TBSRTC. Specifically,
      clinicians are familiar with the percent risk of malignancy corresponding to each
      TBSRTC diagnostic category (DC), as well as with the respective recommendation
      for clinical management. However, most clinicians are much less familiar with the
      specific considerations that lie between a given DC, on the one end, and the
      respective risk of malignancy and associated management recommendation, on the
      other end. SUMMARY: A deeper understanding of the system can enlighten the
      clinician's thinking about the specific nodule under examination and can guide
      the decision-making process in a more meaningful way. Such an understanding can
      only be developed via close two-way communication between cytopathologists and
      clinicians. Through this type of interaction in the authors' tertiary medical
      center, recurring issues of particular importance for clinical practice were
      identified, which are reported here in the form of 16 frequently asked questions
      posed by the clinician to the cytopathologist. CONCLUSIONS: For each frequently
      asked question, an answer is provided based on the literature, the authors'
      experience, the new version of TBSRTC, and the new World Health Organization
      classification of tumors of endocrine organs.

PMID- 29592134
TI  - Erratum.

PMID- 29592135
TI  - Accumulation of Deleterious Mutations in Endosymbionts: Muller's Ratchet with Two
      Levels of Selection.
AB  - Many eukaryotes host mutualistic, maternally transmitted prokaryotic symbionts.
      Two kinds of evolution within symbiont genomes threaten to erode the benefits of
      these associations. First, because symbionts reproduce asexually, are sequestered
      within hosts, and undergo bottlenecks at infection, they are subject to the long
      term accumulation of deleterious mutations through Muller's ratchet. Second,
      "selfish" mutations, benefiting symbionts at host expense, could cause the
      ultimate decline of both host and symbionts. We performed simulations to assess
      how the fate of each mutation type is affected by host population size, numbers
      of symbionts transmitted to progeny, selection within and between hosts, and
      mutation rate. Fixation rate always increases with decreasing host population
      size. However, fixation rates for uniformly deleterious and selfish mutations are
      oppositely affected by varying transmission numbers, with increased numbers
      slowing accumulation of strictly deleterious mutations, especially for effects
      concentrated within hosts, but speeding fixation of "selfish" mutations. In aphid
      symbionts, most genes underlie basic cellular processes and are probably selected
      at both levels, but a substantial minority of genes contribute only to host
      fitness. No inoculum size is optimal for minimizing deleterious evolution for
      both categories of gene.

PMID- 29592136
TI  - The Imprint of History on Communities of North American and Asian Warblers.
AB  - The ecology of the component species of an adaptive radiation is likely to be
      influenced by the form of the founding ancestor to the radiation, its timing, and
      rates of speciation and extinction. These historical features complement
      environmental selection pressures. They imply that, if the history of the
      species' radiations are very different, ecological communities are unlikely to be
      completely convergent even when placed in identical environments. We compare the
      adaptive radiation of the Dendroica warblers of North America with that of the
      Phylloscopus warblers of Asia. We consider the ecology of the species in two
      localities where species' diversity is very high (New Hampshire, U.S.A., and
      Kashmir, India, respectively) and contrast the history of the two radiations on
      the basis of a molecular (mitochondrial cytochrome b) phylogeny. By comparison
      with the Phylloscopus, the Dendroica are on average larger and morphologically
      more similar to one another. Although there is some similarity between the
      Dendroica and Phylloscopus communities, they differ in foraging behavior and in
      associations of morphology with ecological variables. The Dendroica likely
      reflect an early Pliocene radiation and are two to four times younger than the
      Phylloscopus. They probably had a colorful sexually dichromatic ancestor,
      implicating sexual selection in the production of the many ecologically similar
      species. The Phylloscopus are much older and probably had a drab, monomorphic
      ancestor. Given the difference in ages of the two radiations, it is plausible
      that the close species' packing of the Dendroica warblers is a transient
      phenomenon. If this is the case, community structure evolves on the timescales of
      millions of years. Differences in ancestry and timing of the species' radiations
      can be related to the different biogeography of the two regions. This implies
      that the historical imprint on adaptive radiations could be predicted on the
      basis of the attributes of ancestors and biogeographical context.

PMID- 29592137
TI  - Facilitation May Buffer Competitive Effects: Indirect and Diffuse Interactions
      among Salt Marsh Plants.
AB  - Direct interactions among plant species may be highly modified by indirect or
      diffuse effects within a multispecies community. We investigated the direct and
      diffuse effects of two salt marsh perennials, Monanthechloe littoralis and
      Arthrocnemum subterminale, on winter annuals and the perennial herb Limonium
      californicum in a salt marsh in central California. In permanent plots,
      Monanthechloe had expanded substantially in the upper marsh over the past 13 yr,
      while Arthrocnemum and all annual species had decreased. These dynamics suggest
      that Monanthechloe may directly outcompete most other species in the upper marsh.
      In contrast, Arthrocnemum is known to facilitate some annual species. In our
      field experiments, Monanthechloe strongly suppressed Arthrocnemum, all four
      common annual species, and Limonium in direct interactions. In contrast,
      Arthrocnemum directly facilitated the winter annuals Parapholis incurva and
      Lasthenia glabrata, competed with Spergularia marina, and did not have a
      significant effect on Limonium. However, when the combined effects of
      Monanthechloe and Arthrocnemum were tested, Arthrocnemum ameliorated the negative
      effect of Monanthechloe on all four species. Although isolated Arthrocnemum
      competed with Spergularia and had no direct effects on Limonium, Arthrocnemum in
      the presence of Monanthechloe facilitated both species. We hypothesize that
      Arthrocnemum buffered the strong competitive effects of Monanthechloe on
      Lasthenia and Parapholis via direct positive effects and benefited Spergularia
      and Limonium through its competitive effect on Monanthechloe. These findings add
      to the growing body of literature emphasizing the importance of diversity and
      interdependence in the functioning of plant communities.

PMID- 29592138
TI  - How Males Can Gain by Harming Their Mates: Sexual Conflict, Seminal Toxins, and
      the Cost of Mating.
AB  - We suggest that damaging mating tactics, such as physical aggression, the
      evolution of genital barbs and spines, and the transfer of seminal toxins may
      serve as a general means by which males can induce females to avoid or to delay
      remating. Provided that cumulative damage has an accelerating impact on fitness,
      a female who has already been harmed by previous partner(s) may do best to
      refrain from remating to avoid suffering still further damage. Consequently, a
      male can gain through the imposition of mating costs, even though this may reduce
      female fitness because by doing so he minimizes the chances that his mate will
      copulate again. We develop a game theoretical model of this possibility, focusing
      on toxin transfer as an illustrative example. We show that toxicity as a means of
      inhibiting remating is phenotypically stable over a broad range of conditions
      (although, under some circumstances, it may be necessary to invoke other
      selective pressures to account for the initial evolution of toxicity). The model
      predicts that toxin transfer should be more common (and involve greater levels of
      toxicity) in species with greater last-male mating advantage; it is also most
      likely where the poison inflicts strongly accelerating, dose-dependent costs on
      females.

PMID- 29592139
TI  - The Relative Importance of Competition and Predation Varies with Productivity in
      a Model Community.
AB  - Recent theory predicts that productivity can influence the relative importance of
      predation and competition in determining patterns in abundance, diversity, and
      community structure. In low-productivity systems, competition is predicted to be
      the major influence on community patterns, while at high productivity, the major
      influence is predicted to be predation. We directly tested this theory using a
      laboratory model community. Our model community consisted of the bacteriophage T2
      (a virus that feeds on Escherichia coli) and two populations of E. coli, in
      glucose-limited chemostats. One E. coli population consisted of individuals that
      were sensitive to predation by T2 ("vulnerable" E. coli), and the other
      population consisted of individuals that were partially resistant to predation by
      T2 ("less vulnerable" E. coli). We manipulated productivity in this experiment by
      running replicate chemostats with different input concentrations of glucose. Our
      observations were consistent with theoretical predictions. We observed the
      decline of the more vulnerable prey population at higher productivity but not at
      lower productivity, and the decline of the less vulnerable prey population at
      lower productivity but not at higher productivity. However, the rate of decline
      in some replicates was slower than predicted, and extinctions were not observed
      during the experiments, contrary to theoretical predictions. We present some
      testable hypotheses that might explain the slow rate of decline observed.

PMID- 29592140
TI  - Adaptive Evolution of Seed Oils in Plants: Accounting for the Biogeographic
      Distribution of Saturated and Unsaturated Fatty Acids in Seed Oils.
AB  - Structural, energetic, biochemical, and ecological information suggests that
      germination temperature is an important selective agent causing seed oils of
      higher-latitude plants to have proportionately more unsaturated fatty acids than
      lower-latitude plants. Germination temperature is predicted to select relative
      proportions of saturated and unsaturated fatty acids in seed oils that optimize
      the total energy stores in a seed and the rate of energy production during
      germination. Saturated fatty acids store more energy per carbon than unsaturated
      fatty acids; however, unsaturated fatty acids have much lower melting points than
      saturated fatty acids. Thus, seeds with lower proportions of saturated fatty
      acids in their oils should be able to germinate earlier and grow more rapidly at
      low temperatures even though they store less total energy than seeds with a
      higher proportion of saturated fatty acids. Seeds that germinate earlier and grow
      more rapidly should have a competitive advantage. At higher germination
      temperatures, seeds with higher proportions of saturated fatty acids will be
      selectively favored because their oils will provide more energy, without a
      penalty in the rate of energy acquisition. Macroevolutionary biogeographical
      evidence from a broad spectrum of seed plants and the genus Helianthus support
      the theory, as do microevolutionary biogeography and seed germination performance
      within species of Helianthus.

PMID- 29592141
TI  - Is Bergmann's Rule Valid for Mammals?
AB  - Bergmann's rule states that, within species of mammals, individuals tend to be
      larger in cooler environments. However, the validity of the rule has been
      debated. We examined the relationship between size and latitude as well as size
      and temperature within various species of mammals. We also tested the idea that
      smaller mammals follow Bergmann's rule more strongly than larger mammals, as
      expected if heat conservation is the cause of the rule. When all studies were
      included, the percentage of species showing a positive correlation between size
      and latitude was significantly >50% (78 of 110 species). Similarly, the
      percentage of species showing a negative correlation between size and temperature
      was significantly >50% (48 of 64). Analyses using only significant studies or
      only studies that sampled extensively also support Bergmann's rule. The size
      latitude and size-temperature trends were consistent within all orders and most
      families for which data are available. We did not find support for the hypothesis
      that smaller mammals conform more strongly to Bergmann's rule than larger
      mammals. Thus, we found broad support for Bergmann's rule as a general trend for
      mammals; however, our analyses do not support heat conservation as the
      explanation.

PMID- 29592525
TI  - Meis1 is specifically upregulated in kidney myofibroblasts during aging and
      injury but is not required for kidney homeostasis or fibrotic response.
AB  - The homeobox transcription factor Meis1 is required for mammalian development,
      and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1
      is known to be expressed in kidney stroma, but its function in kidney is
      undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in
      kidney development and disease and tested the hypothesis using cell lineage
      tracing and cell-specific Meis1 deletion in development, aging, and fibrotic
      disease. We observed strong expression of Meis1 in platelet-derived growth factor
      receptor-beta-positive pericytes and perivascular fibroblasts, both in adult
      mouse kidney and to a lesser degree in human kidney. Either bilateral ischemia
      reperfusion injury or aging itself led to strong upregulation of Meis1 protein
      and mRNA in kidney myofibroblasts, and genetic lineage analysis confirmed that
      Meis1-positive cells proliferate as they differentiate into myofibroblasts after
      injury. Conditional deletion of Meis1 in all kidney stroma with two separate
      tamoxifen-inducible Cre recombinase drivers had no phenotype with the exception
      of consistent induction of the tubular injury marker kidney injury molecule-1
      (Kim-1) only in Meis1 mutants. Further examination of Kim-1 expression revealed
      linkage disequilibrium of Kim-1 and Meis1, such that Meis1 mutants carried the
      longer BALB/c Kim-1 allele. Unexpectedly, we report that this Kim-1 allele is
      expressed at baseline in wild-type BALB/c mice, without any associated
      abnormalities, including long-term fibrosis, as predicted from the literature. We
      conclude that Meis1 is specifically expressed in stroma and myofibroblasts of
      mouse and human kidney, that it is not required for kidney development, disease,
      or aging, and that BALB/c mice unexpectedly express Kim-1 protein at baseline
      without other kidney abnormality.

PMID- 29592526
TI  - Combination exposure of melamine and cyanuric acid is associated with polyuria
      and activation of NLRP3 inflammasome in rats.
AB  - The molecular mechanisms of melamine-induced renal toxicity have not been fully
      understood. The purpose of the study aimed to investigate whether melamine and
      cyanuric acid induced NOD-like receptor family pyrin domain-containing 3 (NLRP3)
      inflammasome activation in the kidney, which may contribute to abnormal water and
      sodium handling in a rat model. Wistar rats received melamine (Mel; 200 mg.kg
      body wt-1.day-1), cyanuric acid (CA; 200 mg.kg body wt-1.day-1), or Mel plus CA
      (Mel + CA; 100 mg.kg body wt-1.day-1, each) for 2 wk. Mel + CA caused damaged
      tubular epithelial structure and organelles, dilated tubular lumen, and
      inflammatory responses. Crystals were observed in urine and serum specimen, also
      in the lumen of dilated distal renal tubules. The combined ingestion of Mel and
      CA in rats caused a markedly impaired urinary concentration, which was associated
      with reduced protein expression of aquaporin (AQP)1, 2, and 3 in inner medulla
      and alpha-Na-K-ATPase and Na-K-2Cl transporters in cortex and outer medulla. Mel
      + CA treatment was associated with increased protein expression of CD3 and mRNA
      levels of CD68 and F4/80 as well as phosphorylation of NF-kappaB in the kidney.
      Mel + CA treatment increased protein and mRNA expression of NLRP3 inflammasome
      components apoptosis-associated speck-like protein containing a caspase
      recruitment domain, caspase-1, and IL-1beta in the inner medulla of rats. NF
      kappaB inhibitor Bay 11-7082 reduced IL-1beta expression induced by Mel + CA and
      prevented downregulation of AQP2 in inner medullary collecting duct cell
      suspensions. In conclusion, Mel + CA treatment caused urinary-concentrating
      defects and reduced expression of renal AQPs and key sodium transporters, which
      is likely due to the inflammatory responses and activation of NLRP3 inflammasome
      induced by crystals formed in the kidney.

PMID- 29592527
TI  - The association between HIV clinical disease severity and psychiatric disorders
      as seen in Western Romania.
AB  - HIV disease continues to be a serious health issue all over the world. By the end
      of 2016, 36.7 million people were living with HIV, 1.8 million people became
      newly infected and 1 million died of HIV-related causes/diseases. In order to
      develop effective treatment strategies, is important to assess the risk factors
      that affect negatively the HIV-positive patients. HIV-infected patients are at
      high risk of developing psychiatric disorders in every stage of the illness.
      Psychiatric disorders can negatively influence the treatment adherence, induce
      risk behavior and influence the quality of life. The purpose of this study is to
      determine if the severity of HIV disease is associated with increased frequency
      of psychiatric disorders. We evaluated 101 HIV-positive patients receiving
      antiretroviral therapy in Western Romania via Psychiatric Diagnostic Screening
      Questionnaire (PDSQ). We conducted a risk analysis in order to see if the
      patients have a higher risk of developing psychiatric disorders depending on HIV
      serostatus factor (HIV asymptomatic, symptomatic, AIDS converted). Our study
      shows that, the patients having AIDS and symptomatic HIV have a higher prevalence
      for the most common psychiatric disorders: major depressive disorder (OR = 5.81;p
      < 0.001), panic disorder (OR = 3.11; p = 0.016), agoraphobia (OR = 4.31; p =
      0.024), social phobia (OR = 2.81; p = 0.038), generalized anxiety disorder (OR =
      4.79; p = 0.006), somatization (OR = 8.72; p < 0.0010) and hypochondria (OR =
      4.66; p = 0.0013). Symptomatic HIV and AIDS converted serostatus is also a risk
      factor for post-traumatic stress disorder, obsessive-compulsive disorder and
      psychosis. The main conclusion of this study is that the more severe HIV clinical
      disease was associated with increased frequency of psychiatric disorders. As a
      consequence, we conclude that psychiatric disorders and HIV/AIDS treatment should
      be addressed simultaneously, depending on the risk specific factors such as the
      HIV infection stage and, due to psychiatric repercussions of HIV is expected to
      become more relevant in the coming years.

PMID- 29592528
TI  - Barriers and Facilitating Factors for Research Involvement in Cancer Centers: A
      Survey of Colorectal Cancer Center Coordinators in Germany, Austria, and
      Switzerland.
AB  - Improvements in health care depend on research involving health-care providers
      (HCPs) and health-care organizations (HCOs). Existing research suggests that
      involvement in research studies is still much lower than it could be. This study
      investigates factors that may impede or facilitate research involvement. A
      standardized online questionnaire was used to carry out a survey, in 3 countries,
      of key informants in colorectal cancer centers that hold certification in
      accordance with the requirements of the German Cancer Society. A total of 184
      individuals responded (response rate 65%). The respondents found it difficult to
      identify studies suitable for their patients (40% agreement), criticized the
      small overall number of studies available (48%), and found that many studies are
      not worthwhile financially (56%). Among respondents who were not involved in
      studies as the principal investigators (PIs), 66% agreed they lacked the research
      infrastructure needed and 81% that they did not have enough staff. Among
      respondents who were involved as PIs, only 22% indicated that their hospital
      management encouraged them to initiate and conduct clinical trials. Eighty-five
      percent of the respondents agreed that the general population lacks information
      about the importance of studies. Five recommendations for health policy makers
      are derived from these findings for ways of increasing the involvement of HCPs
      and HCOs in research, and in cancer research in particular.

PMID- 29592529
TI  - A novel technique of axillary vein puncture involving peripherally inserted
      central venous catheters for a small basilic vein.
AB  - PURPOSE: Peripherally inserted central venous catheters are some of the most
      useful devices for vascular access used globally. Peripherally inserted central
      venous catheters have a low rate of fatal mechanical complications when compared
      to non-tunnel central venous catheters. However, as peripherally inserted central
      venous catheter access requires a smaller vein, there is a high risk of
      thrombosis. The axillary vein (confluence of the basilic and brachial veins) can
      serve as an access for cannulation. Moreover, as this vein is larger than the
      basilic or brachial vein, it might be a superior option for preventing
      thrombosis. The risk of catheter-related bloodstream infection should be
      considered when the puncture site is at the axillary fossa. The aim of this study
      was to present our new protocol involving peripherally inserted central venous
      catheters (non-tunneled/tunneled) and a tunneling technique and assess its
      feasibility and safety for improving cannulation and preventing thrombosis and
      infection. METHODS: The study included 20 patients. The axillary vein in the
      upper arm was used for peripherally inserted central venous catheters in patients
      with a small-diameter basilic vein (<3 mm). When the puncture site was in the
      axillary fossa, a subcutaneous tunnel of about 3 cm was constructed easily using
      a peripheral venous catheter. RESULTS: The observed catheter duration was 645
      days (median +/- standard deviation, 26 +/- 22.22 days). Catheterization was
      successful in all cases, however, two accidental dislodgements were identified.
      No fatal or serious complications were observed after catheterization.
      CONCLUSION: Our new protocol for axillary peripherally inserted central venous
      catheters/tunneled axillary peripherally inserted central venous catheters use
      for a small-diameter basilic vein is safe and feasible.

PMID- 29592530
TI  - To teach an old dog new tricks: The limits of CHA2DS2-VASc in patients with
      atrial fibrillation and cancer.

PMID- 29592531
TI  - Health literacy in familial hypercholesterolemia: A cross-national study.
AB  - Background High rates of inadequate health literacy are associated with
      maladaptive health outcomes in chronic disease including increased mortality and
      morbidity rates, poor treatment adherence and poor health. Adequate health
      literacy may be an important factor in the effective treatment and management of
      familial hypercholesterolemia, and may also be implicated in genetic screening
      for familial hypercholesterolemia among index cases. The present study examined
      the prevalence and predictors of health literacy in familial hypercholesterolemia
      patients attending clinics in seven countries. Design Cross-sectional survey.
      Methods Consecutive FH patients attending clinics in Australia, Brazil, China,
      Hong Kong, Malaysia, Taiwan and the UK completed measures of demographic
      variables (age, gender, household income and highest education level) and a brief
      three-item health literacy scale. Results Rates of inadequate health literacy
      were lowest in the UK (7.0%), Australia (10.0%), Hong Kong (15.7%) and Taiwan
      (18.0%) samples, with higher rates in the Brazil (22.0%), Malaysia (25.0%) and
      China (37.0%) samples. Income was an independent predictor of health literacy
      levels, accounting for effects of age. Health literacy was also independently
      related to China national group membership. Conclusions Findings indicate non
      trivial levels of inadequate health literacy in samples of familial
      hypercholesterolemia patients. Consistent with previous research in chronic
      illness, inadequate health literacy is related to income as an index of health
      disparities. Chinese familial hypercholesterolemia patients are more likely to
      have high rates of inadequate health literacy independent of income. Current
      findings highlight the imperative of education interventions targeting familial
      hypercholesterolemia patients with inadequate health literacy.

PMID- 29592532
TI  - Thirty-Day and 5-Year Readmissions following First Psychiatric Hospitalization: A
      System-Level Study of Ontario's Psychiatric Care.
AB  - OBJECTIVE: Analyses of representative, system-level data to examine trends in
      short- and longer-term readmission rates for psychiatric illnesses are largely
      absent. The objective of this article is to examine key trends and variables with
      implications for inpatient care as indicated by 30-day readmission and outpatient
      care as reflected by readmission within 5 years. METHODS: Using OMHRS data from
      2005 to 2015, patients who had their first inpatient admission were followed for
      5 years to examine their subsequent 30-day and overall admission rates stratified
      by discharge time and diagnosis. RESULTS: The study cohort consisted of 42,280
      patients. The 30-day and 5-year readmission rates for the entire cohort were 7.2%
      and 35.1%, respectively. Using a time course analysis of readmission for
      discharges in different years, both 30-day readmission and 5-year readmission
      rates decreased in a linear manner from 2005 to 2010, primarily because of
      readmission patterns for patients diagnosed with mood disorders and
      schizophrenia/other psychotic disorders. It was also evident that both
      demographic considerations such as age and gender and variables reflective of
      social determinants such as education level and employment were predictive of
      rehospitalization risk. CONCLUSIONS: The trends of decreasing readmission rates
      may be reflective of improvements in the quality of hospital and community-based
      outpatient care. Such system-level indicators warrant tracking and may inform
      more effective tertiary prevention.

PMID- 29592533
TI  - iStent inject as a reasonable alternative procedure following failed
      trabeculectomy?
AB  - PURPOSE:: The aim of this study is to assess the intraocular pressure lowering
      effect and the performance of the glaucoma therapy of the iStent inject in
      glaucoma patients with uncontrolled intraocular pressure after failed
      trabeculectomy. METHODS:: In this retrospective study, iStent inject implantation
      (Glaukos Corporation, Laguna Hills, CA, USA) was performed in 22 eyes of 21
      subjects suffering from glaucoma (n = 18 primary open angle glaucoma, n = 3
      pseudoexfoliation glaucoma, and n = 1 for secondary glaucoma) with an intraocular
      pressure above target pressure after failed trabeculectomy (mean = 9.6 +/- 8.1
      years; range: 1-35 years). The intraocular pressure and the number of
      antiglaucomatous medication were assessed preoperatively, 1 day, 6 weeks, 3
      months, 6 months, and 1 year after surgery and compared to preoperative findings
      (SPSS v23.0; Shapiro-Wilk test, Wilcoxon test, Friedman test). RESULTS:: The
      results showed a significant intraocular pressure decrease from 22.5 +/- 4.6 to
      15.5 +/- 3.4 mmHg after 1 year follow-up (p = 0.012). The glaucoma therapy was
      2.6 +/- 1.2 preoperatively and reduced to 2.25 +/- 1.5 number of medications
      after 1 year (p > 0.05). There was no significant difference in the number of
      medication during the whole follow-up period (1 year, p = 0.012). No significant
      intra- or postoperative complications were reported. CONCLUSION:: Minimal
      invasive glaucoma surgery (iStent inject) can offer an effective intraocular
      pressure reduction in advanced adult primary and secondary open angle glaucoma
      after failed trabeculectomy in a follow-up period of 1 year. Glaucoma therapy,
      however, needs to be maintained to achieve an individual target pressure and to
      prevent glaucoma progression. In addition, a failure rate of 27.3% makes it
      necessary to select carefully patients for this treatment option.

PMID- 29592535
TI  - Commentary on Some Recent Theses Relevant to Combating Aging: April 2018.

PMID- 29592534
TI  - [End-of-Life Care in Intensive Care Units: Nursing strategies of family
      involvement at the end of life].
AB  - Background: Family members of people dying in the intensive care unit (ICU) are
      exposed to many stress factors and they often do not experience involvement in
      End-of-Life (EoL) situations. For example, they criticize a low degree of
      participation in patients care, delayed or incomplete information and lack of
      privacy. Even nursing staff is facing various obstacles in EoL situations in
      ICUs. Aim: This study investigates strategies used by ICU nursing staff in German
      speaking Switzerland to increase family members participation in situations at
      the end of life. Method: Data was collected by conducting 12 semi-structured
      interviews using an approach based on Grounded Theory. A model was developed to
      explain nursing strategies for family involvement in EoL situations in the ICU.
      Conclusions: Nurses provide personal space and tranquillity for family members
      and allow them to be present at any time. Against this background, they support
      family members and enable them to say goodbye consciously to a loved one.
      Subsequent work should examine the effectiveness of the strategies described,
      particularly in terms of stress reactions displayed by family members in the
      aftermath of EoL situations. In practice, family members should be provided space
      for privacy. The entire healthcare team is recommended to identify and pursue
      common values and objectives. Moreover, intradisciplinary exchange and mentoring
      need to be encouraged. In order to prepare future nursing staff for EoL
      situations in the ICU, recognizing and promoting their educational skills is
      mandatory.

PMID- 29592536
TI  - ["Alone with the taboo" - The social support experienced by women with vulvar
      neoplasia: a qualitative study].
AB  - : "Alone with the taboo" - The social support experienced by women with vulvar
      neoplasia: a qualitative study Abstract. BACKGROUND: Cancer of the vulva is a
      gynaecological disease often with relevant impact for these women's daily life.
      On top of the medical complications, psychological problems might arise as well,
      due to the impaired quality of life and the withdrawal from social life. We do
      not know whether and what type of support is given to these patients. AIM: The
      qualitative study aimed at describing how the affected women experience the
      support they receive from their social environment from the time of the diagnosis
      to six months postoperatively. METHODS: A qualitative design was used. In a
      secondary analysis, 20 transcribed interviews from the WOMN-PRO study were
      analysed by qualitative content analysis according to Mayring. RESULTS: The
      findings from the study resulted in four main categories: having a serious
      disease shows how the patients experience the diagnosis as a shock and are
      confronted with questions of guilt and taboos. The category feel alone was
      strongly represented with features of not-speaking out, not looking at it and not
      acting. Do it on your own features descriptions of the strategies the women use
      to get out of their loneliness. In experience help, it is shown that women who
      try to get in touch with their social environment usually receive support.
      CONCLUSIONS: Patients have a high demand for information concerning the disease
      and its possible impacts on their daily life as well as emotional and practical
      support from their families / partners and especially from health professionals.
      We recommend designating someone who acts throughout the whole treatment process
      as a mediator and a person of trust.

PMID- 29592537
TI  - Identification of the Medication Regimen Complexity Index as an Associated Factor
      of Nonadherence to Antiretroviral Treatment in HIV Positive Patients.
AB  - BACKGROUND: Multiple studies have identified a relationship between the
      complexity of a medication regimen and non-adherence. However, most studies in
      people who live with HIV (PLWH) have focused on antiretroviral use and have
      failed to consider the impact of other medications. OBJECTIVE: The aim of our
      study is to identify the Medication Regimen Complexity Index (MRCI) as an
      associated factor for nonadherence to antiretroviral treatment (ART). The
      secondary aim is to analyze the relationship between clinical and
      pharmacotherapeutical variables and adherence to antiretroviral treatment and to
      generate an adherence model. METHODS: A transversal, observational study.
      Patients included were PLWH over 18 years of age on active antiretroviral
      therapy. Patients who participated in clinical trials or who did not meet the
      inclusion criteria were excluded. We had studied HIV transmission mode, viral
      load, treatment status, number of comorbidities and complexity index as factors
      associated with adherence to ART. RESULTS: We included 619 patients in the study.
      Number of comorbidities ( p = 0.021; OR = 1.038-1.570); viral load ( p = 0.023;
      OR = 1.108-4.505) and MRCI ( p < 0.001; OR = 1.138-1.262) (ART and concomitant
      treatment) were the independent associated factors to ART nonadherence. The value
      of the Hosmer and Lemeshow test confirmed the validity of this model (P = 0.333).
      CONCLUSION: A higher MRCI was associated with non-adherence. Therefore, the
      regimen complexity calculation may be appropriate in daily practice for
      identifying patients at a higher risk of becoming non-adherent.

PMID- 29592538
TI  - Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing
      Recommendations.
AB  - OBJECTIVE: To review the literature on both thromboprophylaxis and treatment of
      venous thromboembolism (VTE) with enoxaparin in low- and high-body-weight
      patients and to make dosing and monitoring recommendations in these patient
      populations. DATA SOURCES: A search using PubMed was conducted (1995 to January
      2018) using the following key words: enoxaparin, body weight, AND
      thromboprophylaxis, or AND treatment. Additional references were identified from
      a review of citations. STUDY SELECTION AND DATA EXTRACTION: Studies included
      examined the effect of body weight and/or body mass index (BMI) on VTE, bleeding,
      enoxaparin dosing, and/or anti-Xa concentrations for thromboprophylaxis and
      treatment-dose enoxaparin. Studies in pediatric and pregnant patients were
      excluded. DATA SYNTHESIS: Optimal enoxaparin dosing strategies for VTE
      prophylaxis and treatment for patients at extremes of weight have not yet been
      elucidated by clinical trials; however, data suggest that standard dosing
      regimens may not be appropriate in these patients. Relevance to Patient Care and
      Clinical Practice: This review provides a thorough discussion on both
      thromboprophylaxis and treatment of VTE with enoxaparin in low- and high-body
      weight patients. It includes dosing recommendations to guide clinicians caring
      for these patient populations. CONCLUSIONS: Patients at extremes of weight
      require special consideration to determine appropriate enoxaparin doses.
      Specifically, low-body-weight patients may benefit from 30 mg subcutaneously
      daily for VTE prophylaxis, and standard weight-based dosing for VTE treatment.
      Conversely, in patients with BMIs >=40 kg/m2, 40 mg subcutaneously twice daily is
      recommended, with consideration for higher doses in patients with BMIs >=50
      kg/m2.

PMID- 29592539
TI  - Pharmacotherapy in Acutely Anemic Jehovah's Witnesses: An Evidence-Based Review.
AB  - OBJECTIVE: To determine the pharmacological treatment methods available to anemic
      Jehovah's Witnesses (JW). DATA SOURCES: MEDLINE and PubMed were searched from
      inception through February 2018 using the search terms Jehovah's Witnesses,
      treatment, erythropoietin, hemoglobin-based oxygen carrier, Sanguinate, Hemopure,
      bleeding, and anemia. STUDY SELECTION AND DATA EXTRACTION: All clinical trials,
      cohort studies, case-control studies, and observational trials involving
      pharmacotherapy in anemic JW patients were evaluated. Case reports and
      bibliographies were also analyzed for inclusion. DATA SYNTHESIS: Two studies
      involving the use of erythropoietin (EPO) and one study involving recombinant
      factor VIIa were included. Information was also included from other
      pharmacotherapeutic modalities that had case report data only. Current published
      evidence is limited with regard to evidence-based management of JW patients. High
      dose EPO, intravenous iron supplementation, and hemostatic agents have
      demonstrated good clinical outcomes in case reports. EPO doses as high as 40 000
      units daily have been advocated by some experts; however, pharmacokinetic studies
      do not support dose-dependent effects. Hemoglobin-based oxygen carriers (HBOCs)
      are currently not Food and Drug Administration approved. They are available
      through expanded access programs and may represent a lifesaving modality in the
      setting of severe anemia. CONCLUSIONS: There are currently not enough data to
      make definitive recommendations on the use of pharmacological agents to treat
      severe anemia in the JW population. Further evidence utilizing EPO and HBOCs will
      be beneficial to guide therapy.

PMID- 29592540
TI  - Reported Problems and Adherence in Using Asthma Medications Among Adolescents and
      Their Caregivers.
AB  - BACKGROUND: Many factors affect youth adherence to asthma medications. Better
      understanding of the relationship between problems reported by youth in using
      asthma medications, self-efficacy, outcome expectations, and adherence is needed.
      OBJECTIVE: The study examined the relationship between youth and caregiver
      problems in using asthma medications, asthma management self-efficacy, outcome
      expectations, and youth- and caregiver-reported adherence to asthma controller
      medications. METHODS: Adolescents with persistent asthma and their caregivers
      were recruited at 4 pediatric practices. Youth were interviewed after their
      medical visit while caregivers completed a questionnaire. Multivariable linear
      regression was used to analyze the data. RESULTS: Of 359 participating youth, 319
      were on controller medications. Youth reported 60% average adherence, whereas
      caregivers reported 69%. Youth who reported difficulty using their inhaler
      correctly and youth who reported difficulty remembering to take their medications
      were significantly less likely to be adherent. Caregivers who reported that it
      was hard to remember when to give the asthma medications were significantly less
      likely to report their child being adherent. Both youth and caregivers with
      higher outcome expectations were significantly more likely to self-report being
      adherent. CONCLUSIONS: Pharmacists and other health care providers should
      consider asking youth and caregivers about problems in using asthma medications,
      self-efficacy in managing asthma, and outcome expectations for following
      treatment regimens, so that they can help youth overcome difficulties they might
      have in managing their asthma.

PMID- 29592541
TI  - Egg Load Evolution in Parasitoids.
AB  - Parasitic wasps lay their eggs in or on other insects. Allocation of resources to
      reproduction (eggs) and survival (life span) should maximize reproductive
      success, but stochasticity in the number of hosts encountered precludes an exact
      match of allocation with reproductive opportunity. We study optimal egg loads
      using a general model for pro-ovigenic parasitoids (which only mature eggs before
      adult life) and a dynamic programming model for synovigenic parasitoids (which
      can mature additional eggs during adult life). We find that stochasticity has a
      major effect on optimal egg loads and that the patchy distribution of hosts is
      the major source of stochasticity in reproductive opportunities. In a stochastic
      world, the further "relative habitat quality" (expected number of oviposition
      opportunities gained by reducing reproductive investment by one egg) is below
      unity (as we argue it generally is), the more the optimal egg load exceeds the
      expected number of hosts. In unusually rich environments, however, stochasticity
      decreases optimal egg loads. Although synovigenic parasitoids can adjust to the
      conditions they encounter, they too have to invest for an uncertain future.
      Because they can replenish their egg supply throughout life, the incidence of egg
      limitation is even lower than in pro-ovigenic parasitoids.

PMID- 29592542
TI  - Legume Sanctions and the Evolution of Symbiotic Cooperation by Rhizobia.
AB  - The legume-rhizobium symbiosis is an ideal model for studying the factors that
      limit the evolution of microbial mutualists into parasites. Legumes are unable to
      consistently recognize parasitic rhizobia that, once established inside plant
      cells, use plant resources for their own reproduction rather than for N2
      fixation. Evolution of parasitism in rhizobia, driven partly by competition among
      multiple rhizobial strains infecting the same plant, may be countered by
      postinfection legume sanctions. Both the biochemical options for rhizobial
      cheating and the evolutionary effect of legume sanctions depend on differences in
      rhizobial life history associated with nodule type. In legumes with determinate
      nodule growth, rhizobia typically retain the ability to reproduce after
      differentiating into N2-fixing bacteroids. Sanctions against individual
      bacteroids (e.g., acid hydrolases) would therefore select for cooperative
      rhizobia. In nodules with indeterminate growth, bacteroids generally lose the
      ability to reproduce, so legume sanctions against bacteroids would have no effect
      on rhizobial evolution. Whole-nodule sanctions (e.g., decreased nodule O2
      permeability) could be effective, via kin selection of undifferentiated rhizobia
      that persist in indeterminate nodules and replenish soil populations after nodule
      senescence. Mixed nodules could reduce the effectiveness of whole-nodule
      sanctions. The frequency of mixed nodules under field conditions is unknown.

PMID- 29592543
TI  - The Origin of Interspecific Genomic Incompatibility via Gene Duplication.
AB  - One of the great unsolved mysteries of evolutionary biology concerns the genetic
      mechanisms underlying the origin of genomic incompatibilities between species.
      Two prevailing thoughts are that such incompatibilities often result from
      epistatically interacting genes that act as loss-of-function alleles in hybrid
      backgrounds or from chromosomal rearrangements that result in mis-segregation
      during meiosis in hybrids. However, it is unclear how genes that cause a radical
      breakdown in hybrids arise without reducing fitness within species, and numerous
      cases of speciation appear to be unassociated with obvious chromosomal
      rearrangements. Here we suggest that duplicate genes, and more generally any kind
      of genomic redundancies, provide a powerful substrate for the origin of genomic
      incompatibilities in isolated populations. The divergent resolution of genomic
      redundancies, such that one population loses function from one copy while the
      second population loses function from a second copy at a different chromosomal
      location, leads to chromosomal repatterning such that gametes produced by hybrid
      individuals can be completely lacking in functional genes for a duplicate pair.
      Under this model, incompatibility factors accumulate with essentially no loss of
      fitness within populations as postulated under the Bateson-Dobzhansky-Muller
      (BDM) model of speciation and despite the fact that they arise from degenerative
      mutations. However, unlike the situation often envisioned under the BDM model, no
      change in the mode of gene action in hybrid backgrounds need be invoked. The
      plausibility of this model derives from a number of recent observations,
      including the fact that most genomes harbor substantial numbers of gene
      duplicates whose turnover is common and ongoing process and the fact that many
      genes have complex regulatory regions that facilitate their divergent resolution
      in sister taxa.

PMID- 29592544
TI  - Specialized Feeding Behavior Influences Both Ecological Specialization and
      Assortative Mating in Sympatric Host Races of Pea Aphids.
AB  - Not only is ecological specialization a defining feature of much of Earth's
      biological diversity, the evolution of specialization may also play a central
      role in generating diversity by facilitating speciation. To understand how
      ecological specialization evolves, we must know the particular characters that
      cause organisms to be specialized. For example, most theories of specialization
      in herbivorous insects emphasize physiological trade-offs in response to toxic
      plant chemicals. However, even in herbivores, it is likely that other characters
      are also involved in resource specialization. Knowing the causes of ecological
      specialization is also crucial for linking specialization to speciation. When the
      same character(s) that cause specialization also influence assortative mating,
      speciation may occur particularly rapidly because specialization and reproductive
      isolation become coupled in a positive feedback that speeds the evolution of
      both. Indeed, a central hypothesis in the study of ecological speciation is that
      specialization in recently diverged taxa may often be due to characters that also
      produce assortative mating. We test this hypothesis by evaluating the causes of
      ecological specialization among host-associated populations of an herbivorous
      insect, the pea aphid (Acyrthosiphon pisum). These populations are highly
      specialized on different host plants (alfalfa or clover; "alternate hosts"), and
      the races are partially reproductively isolated. Here, we identify key characters
      responsible for host plant specialization. Our results suggest that the major
      proximal determinant of host specialization is the behavioral acceptance of a
      plant rather than the toxicity of the food source. Pea aphids rapidly assess
      alfalfa and clover and reject the alternate host based on chemical cues that are
      perceived before the initiation of feeding. This rapid behavioral rejection of
      the alternate host by a given race has two consequences. First, unrestrained
      aphids quickly leave the alternate host and search for other plants. Because pea
      aphids mate on their host plants, divergence in host acceptance among
      ecologically specialized races leads to congregation on the favored host. This
      results in de facto assortative mating when sexual forms are produced in late
      summer. Second, specialized aphids that are held on the alternate host will not
      feed in a 7.2-h trial, even in the face of starvation. Thus, a complex trait,
      behavioral acceptance of a plant as host, influences both reproductive isolation
      (through host-associated assortative mating) and ecological specialization
      (because of low nutritional uptake on the alternate host). This dual influence of
      feeding behavior on both assortative mating and resource specialization is
      central to the maintenance of these divergent races, and it may also have been
      involved in their origin.

PMID- 29592545
TI  - Sex Allocation and Reproductive Success in the Andromonoecious Perennial Solanum
      carolinense (Solanaceae). II. Paternity and Functional Gender.
AB  - According to Bateman's principle, male fitness in entomophilous plant species
      should be limited by mating opportunity, which is influenced by the size or
      number of flowers. We determined male-specific fitness consequences of floral
      phenotype in andromonoecious Solanum carolinense, examined the relationship
      between male and female reproductive success within plants, and evaluated the
      distribution of functional gender among plants. A maximum likelihood-based
      paternity analysis, based on multilocus allozyme phenotypes of parents and
      offspring from four experimental plots, was used to determine male reproductive
      success and its relationship to floral phenotype. Male success was enhanced by an
      increase in the proportion of male flowers produced but not by an increase in
      total flower number, even though all flowers contain male parts. Larger flower
      size increased male success in only one plot. Male and female reproductive
      success were negatively correlated, and plants varied in functional gender from
      completely female to completely male. This gender specialization may occur
      because hermaphroditic and male flowers differ in their ability to contribute to
      male and female success. Although sex allocation theory predicts a positive
      relationship between the size or number of plant parts and reproductive success,
      this study indicates that aspects of floral morphology that affect gender
      specialization should also be considered.

PMID- 29592546
TI  - Begging and Parental Care in Relation to Offspring Need and Condition in the Barn
      Swallow (Hirundo rustica).
AB  - Parents are selected to maximize their fitness by allocating care among their
      progeny in relation to the differential reproductive value of offspring.
      Nestlings have been hypothesized to signal need for parental care reliably
      through their begging behavior, but offspring condition as reflected by their
      reproductive value may likewise affect begging and hence provisioning. We
      assessed the relative importance of need and condition in determining begging
      behavior and feeding rate of nestling barn swallows (Hirundo rustica) through
      short-term starvation, a challenge to their immune system with a foreign antigen
      negatively affecting condition, and brood size manipulation. Food deprivation but
      not condition or brood size manipulation increased nestling begging rate. Parents
      fed offspring depending on both need and condition but only when feeding broods
      that were reduced or of normal size. In enlarged broods, offspring received less
      food per capita than in reduced broods, and parents did not discriminate among
      nestlings relative to their need or condition. Thus, nestlings signal their need
      by increased solicitation. Parents allocate food to offspring dependent on both
      need and condition, with these effects depending on parental workload as
      determined by experimental brood size.

PMID- 29592547
TI  - Measuring and Using Skew in the Study of Social Behavior and Evolution.
AB  - Unequal distribution of benefits from cooperation is a fundamental feature of
      social behavior, and many quantitative measures of this skew have been proposed.
      Overall group size and productivity affect each of the measures somewhat
      differently depending on their formulation. Some of the differences are due to
      whether the index is intended to measure skew relative to a random distribution
      or relative to the maximum possible skew. Sampling errors, however, will tend to
      make smaller and less productive groups seem more skewed than they actually are.
      Differential survival or residence times of group members add a second factor
      that can result in skew independent of behavioral mechanisms. Thus, significant
      biases can result in indices that do not account for random processes or
      differential survival within groups. Seven published skew indices plus a new
      index (B) that combines observed variance with the expected binomial variance
      were tested across simulations that compared groups varying in resource
      distribution probabilities, size, or productivity. Only the B index always
      avoided error through correctly adjusting for group size, productivity, and
      differential residence times. Thus, the B index has the best potential to be a
      benchmark value that can be used for identifying evolutionary patterns in social
      behavior, both across and especially within species. Although skew indices have
      been applied mostly to shared reproduction, the B index is suitable to any
      situation where group members divide benefits. Skew indices potentially can
      identify and test evolutionary scenarios across a wide range of behavioral
      interactions, such as dominance hierarchies, information exchange, and parental
      care.

PMID- 29592580
TI  - Studies of Adaptive Radiation Using Model Microbial Systems.
AB  - Adaptive radiation is a fundamental process in the evolution of biodiversity. The
      effects of seasonality, resource partitioning, and spatial heterogeneity have
      been examined experimentally using evolving populations of microbes. In all
      environmental conditions examined, ecological interactions have large effect on
      the likelihood and outcome of adaptive radiation. Adaptive radiation in seasonal
      environments can arise because of demographic trade-offs and excretion of
      metabolites. Resource partitioning can occur even in the absence of temporal or
      spatial heterogeneity. Spatial heterogeneity arising via growth is sufficient to
      generate microenvironments and subsequent adaptive radiation. However, ecological
      interactions maintaining diversity can be sensitive to slight alterations of the
      environmental conditions. Laboratory populations of microbes are ideal model
      systems to test the factors essential for adaptive radiation.

PMID- 29592581
TI  - Character Shifts of Prey Species That Share Predators.
AB  - This article uses several models to explore the potential indirect evolutionary
      interaction between two prey species that share one or more predator species. It
      asks how the antipredator adaptations of a focal prey species are likely to
      evolve following the introduction of a second prey species that shares one or
      more of the same predator species. The interactions are represented by
      differential equation models of homogeneous populations, and evolutionary change
      occurs in a single quantitative trait within each prey species. Models differ in
      assumptions about the number of predator types, the costs of antipredator traits,
      and in how predator and prey traits combine to determine a per capita capture
      rate. Parallel change in the antipredator characteristics of two species usually
      occurs when the general risk of predation is changed by the introduction of the
      second prey. This may be a parallel increase or decrease, depending on whether
      the ecological interaction is apparent competition or apparent mutualism.
      Divergence in trait values is most often associated with the presence of two or
      more distinct types of predators with some form of trade-off in the prey's
      ability to avoid different predators. Divergence may also occur with a single
      predator type, when two or more strategies exist for reducing predation risk.
      Convergence is a possible outcome when there are two or more predator types.
      Coevolution may also produce trait and population cycles in models, and the
      nature of character displacement is often changed markedly by such instability.
      The limited evidence for evolutionary indirect effects mediated by shared
      predation is reviewed. Possible reasons for the disparity between theory and
      observation are discussed.

PMID- 29592582
TI  - Reversal of Mutualism as a Mechanism for Adaptive Radiation in Yucca Moths.
AB  - Species interactions are a major source of adaptive radiation. In mutualisms,
      such diversification can take the form of evolution of parasites that exploit the
      resources needed for maintenance of the mutualism. Mutualistic associations often
      have associated parasitic species, and in some cases, parasitic species have
      indeed evolved from the mutualists. For example, obligate mutualisms, such as
      those involving seed-eating pollinators, have on a few occasions given rise to
      nonmutualist species. These systems are relatively simple and provide models for
      identifying factors that facilitate the stable reversal of a mutualistic
      interaction. We used ecological data in a phylogenetic framework to analyze the
      origins of two nonmutualist cheater yucca moths. Phylogenetic analysis suggests
      that the evolution of cheating may be preceded by a change in oviposition
      behavior. Two different modes of oviposition among moth species cause density
      dependent moth egg mortality through flower abscission in one case (locule
      ovipositing species) but density-independent mortality in the other
      (superficially ovipositing species). A mtDNA-based phylogeny indicated that
      cheating and superficial oviposition have evolved twice each and that the cheater
      clades are sisters to the superficially ovipositing species clades. Consideration
      of the fitness consequences of two trait changes-loss of pollination and
      phenological delay in oviposition-in which cheaters have diverged from ancestral
      pollinators suggest that the shift to oviposition into fruit may have occurred
      first and that loss of pollination behavior was a secondary event. We suggest
      that secondary coexistence of two pollinator species of opposite oviposition
      modes may facilitate the shift to fruit oviposition and cheating and that this is
      applicable in the best documented of the cheater yucca moths. Superficially
      ovipositing species suffer dual sources of egg mortality when in coexistence with
      locule-ovipositing species. Shift to fruit oviposition under this circumstance
      can be facilitated by access to a seed resource not available to the
      copollinator, preadaptations in ovipositor morphology, and pollinator phenology
      late relative to the copollinator. Thus the adaptive radiation of nonmutualists
      from mutualists may have taken place in specific ecological contexts through few
      trait changes, and the reversal of mutualism would be a by-product of a shift to
      reliance on a previously inaccessible seed resource.

PMID- 29592583
TI  - Evolutionary Branching and Sympatric Speciation Caused by Different Types of
      Ecological Interactions.
AB  - Evolutionary branching occurs when frequency-dependent selection splits a
      phenotypically monomorphic population into two distinct phenotypic clusters. A
      prerequisite for evolutionary branching is that directional selection drives the
      population toward a fitness minimum in phenotype space. This article demonstrates
      that selection regimes leading to evolutionary branching readily arise from a
      wide variety of different ecological interactions within and between species. We
      use classical ecological models for symmetric and asymmetric competition, for
      mutualism, and for predator-prey interactions to describe evolving populations
      with continuously varying characters. For these models, we investigate the
      ecological and evolutionary conditions that allow for evolutionary branching and
      establish that branching is a generic and robust phenomenon. Evolutionary
      branching becomes a model for sympatric speciation when population genetics and
      mating mechanisms are incorporated into ecological models. In sexual populations
      with random mating, the continual production of intermediate phenotypes from two
      incipient branches prevents evolutionary branching. In contrast, when mating is
      assortative for the ecological characters under study, evolutionary branching is
      possible in sexual populations and can lead to speciation. Therefore, we also
      study the evolution of assortative mating as a quantitative character. We show
      that evolution under branching conditions selects for assortativeness and thus
      allows sexual populations to escape from fitness minima. We conclude that
      evolutionary branching offers a general basis for understanding adaptive
      speciation and radiation under a wide range of different ecological conditions.

PMID- 29592584
TI  - Comparative Analysis of Character Displacement and Spatial Adaptations as
      Illustrated by the Evolution of Dalechampia Blossoms.
AB  - We describe a phylogenetic and spatial approach to the comparative study of
      character displacement and other coevolutionary phenomena. The method is
      developed as an in-depth study of blossom morphology in 37 populations of the
      Neotropical vine Dalechampia scandens. We test the hypothesis that among
      population variation in blossom morphology is due largely to local adaptation to
      avoid competition from other species of Dalechampia that utilize the same
      restricted set of pollinators. Because direct phylogenetic and historical
      information are unavailable for these populations, we develop a novel comparative
      method for the study of adaptation to a spatially distributed selective factor in
      spatially correlated populations. In addition to providing spatially, or
      phylogenetically, corrected estimates of selective effects, the method assesses
      the local specificity of adaptations. We find evidence for moderately strong
      local specificity of adaptation among our populations, and furthermore we find
      that the effects of putative competitors are in accordance with predictions from
      a hypothesis of character displacement. However, sympatry or allopatry explains
      only 10%-20% of the interpopulation variation in blossom morphology, and we
      therefore cannot exclude the possibility that some other selective factors are
      major determinants of the variation.

PMID- 29592585
TI  - Individual Value Clarification Methods Based on Conjoint Analysis: A Systematic
      Review of Common Practice in Task Design, Statistical Analysis, and Presentation
      of Results.
AB  - BACKGROUND: There is an increased practice of using value clarification exercises
      in decision aids that aim to improve shared decision making. Our objective was to
      systematically review to which extent conjoint analysis (CA) is used to elicit
      individual preferences for clinical decision support. We aimed to identify the
      common practices in the selection of attributes and levels, the design of choice
      tasks, and the instrument used to clarify values. METHODS: We searched Scopus,
      PubMed, PsycINFO, and Web of Science to identify studies that developed a CA
      exercise to elicit individual patients' preferences related to medical decisions.
      We extracted data on the above-mentioned items. RESULTS: Eight studies were
      identified. Studies included a fixed set of 4-8 attributes, which were
      predetermined by interviews, focus groups, or literature review. All studies used
      adaptive conjoint analysis (ACA) for their choice task design. Furthermore, all
      studies provided patients with their preference results in real time, although
      the type of outcome that was presented to patients differed (attribute importance
      or treatment scores). Among studies, patients were positive about the ACA
      exercise, whereas time and effort needed from clinicians to facilitate the ACA
      exercise were identified as the main barriers to implementation. DISCUSSION:
      There is only limited published use of CA exercises in shared decision making.
      Most studies resembled each other in design choices made, but patients received
      different feedback among studies. Further research should focus on the feedback
      patients want to receive and how the CA results fit within the patient-physician
      dialogue.

PMID- 29592605
TI  - A Systematic Review of Caregiver-Implemented Mealtime Interventions for Children
      With Autism Spectrum Disorder.
AB  - Children with autism spectrum disorder (ASD) frequently have difficult mealtimes.
      A systematic review analyzed current evidence relevant to occupational therapy
      (OT) and mealtime interventions (a) for children with ASD, (b) occurring in the
      natural contexts, and (c) with parents/caregivers as interventionists. Database
      search identified 13 relevant articles. Each article was reviewed for
      practicality of implementation through a modified Feasibility, Appropriateness,
      Meaningfulness and Effectiveness (FAME) scale and for quality of research design
      using three measures specifically designed for single-case experimental design
      research. The majority of articles reviewed demonstrated rigorous research design
      with strong evidence for the effectiveness of caregiver-implemented
      interventions. Six intervention techniques were identified, with all studies
      using a reinforcement strategy and at least one other technique. This review
      identifies evidence-based practices for OTs to support children with ASD and
      their families within the natural co-occupation of mealtimes. Effective
      techniques and recommendations for practice are included.

PMID- 29592634
TI  - Risk Factors Associated With Peripheral Neuropathy in Heart Failure Patients
      Candidates for Transplantation.
AB  - INTRODUCTION: Peripheral neuropathy can affect patients with heart failure,
      though its prevalence is unknown. After heart transplantation, it can influence
      the postoperative course and quality of life, but screening for neuromuscular
      disease is not routinely performed. OBJECTIVE: The aim of this study was to
      identify the factors associated with neuropathy in a population of patients with
      heart failure who are candidates for heart transplantation. STUDY DESIGN: Data
      regarding patients' clinical history, including recent hospitalizations, were
      collected. All patients underwent a complete neurological examination and a
      neurophysiological protocol including nerve conduction studies and concentric
      needle electromyography. RESULTS: Thirty-two patients were included in the study,
      and neuropathy was diagnosed in 10 (31.3%). Neuropathy was associated with the
      number of admissions ( P = .023; odds ratio [OR]: 1.96) and the total number of
      days of hospitalization in the year prior to inclusion in the study ( P = .010;
      OR: 1.03). The majority of hospitalizations occurred in the step-down unit (85%),
      with acute heart failure the leading cause of admission (42%). CONCLUSIONS: This
      study shows that neuropathy is frequent in patients with advanced heart failure
      and that hospitalization for cardiac care, also in the absence of intensive care,
      is a marker of high risk of neurologic damage. These data can help physicians in
      selecting and managing candidates for transplantation and can guide decisions on
      the best immunosuppressive regimen or rehabilitation strategy.

PMID- 29592635
TI  - How Inaccurate Metrics Hide the True Potential for Organ Donation in the United
      States.
AB  - BACKGROUND: There is a discrepancy between the reported increase in donor
      conversion rates and the number of organs available for transplant. METHODS:
      Secondary analysis of data obtained from the Scientific Registry of Transplant
      Recipients from January 2003 through December 2015 was performed. The primary
      outcomes were the (1) number of brain-dead donors from whom solid organs were
      recovered and (2) number of the organs transplanted. Descriptive statistics and
      growth plots were used to examine the trajectory of organ donation, recovery, and
      transplantation outcomes over the 11-year period. RESULTS: From 2003 to 2006, the
      number of brain-dead donors increased from 6187 to 7375, remaining relatively
      stable at approximately 7200 thereafter. The average eligible deaths per organ
      procurement organization dropped from 182.7 (standard deviation [SD]: 131.3) in
      2003 to 149.3 (SD: 111.4) in 2015. This suggests a total of 12 493 unrealized
      potential donors (2006-2015). CONCLUSIONS: Since 2006, a steady decline in the
      number of donor-eligible deaths was reported. In 2003, the reported eligible
      deaths was 11 326. This number peaked in 2004 at 11 346, tumbling to 9781
      eligible donors in 2015, despite a 9% increase in the US population. From 2006 to
      2015, the data indicate an artificial depression and underestimation of the true
      potential of brain-dead donors in the United States of conservatively 12 493
      donors or 39 728 missing organs. New metrics providing objective but verifiable
      counts of the donor pool are needed.

PMID- 29592637
TI  - To Have Seen or Not to Have Seen: A Look at Rensink, O'Regan, and Clark (1997).
AB  - Rensink, O'Regan, and Clark drew attention to the phenomenon of change blindness,
      in which even large changes can be difficult to notice if made during the
      appearance of motion transients elsewhere in the image. This article provides a
      sketch of the events that inspired that article as well as its subsequent impact
      on psychological science and on society at large.

PMID- 29592636
TI  - The Error-Related Negativity, Self-Monitoring, and Consciousness.
AB  - The error-related negativity (ERN) is a negative waveform that arises over the
      front of the scalp immediately after a participant makes a detectable error. The
      goal of this short article is to describe my serendipitous encounter with this
      brain signal in 1993-1994 and to briefly review the operation of the underlying
      error-monitoring system. Recent work suggests that the ERN reflects an internal
      comparison, by the anterior cingulate cortex, of two signals: an unconscious
      representation of the ongoing action and a conscious representation of the
      intended one.

PMID- 29592638
TI  - Revisiting Our Reappraisal of the (Surprisingly Few) Benefits of High Self
      Esteem.
AB  - Our 2003 article clashed with conventional wisdom by concluding that high self
      esteem has only a couple of benefits, notably high initiative (based on trusting
      one's own judgment) and feeling good. Its high citation rate reflects not only
      the novel conclusions but also widespread interest in self-esteem both among
      researchers and in the broader society. Psychology may have lost some credibility
      by advocating efforts to raise self-esteem that were based on correlational
      evidence, which may be a salutary lesson for the field. There is still much to
      learn about self-esteem, but future work can improve by noting weaknesses in self
      report data and correcting for confounds.

PMID- 29592639
TI  - Sexual and Emotional Infidelity: Evolved Gender Differences in Jealousy Prove
      Robust and Replicable.
AB  - Infidelity poses threats to high-investment mating relationships. Because of
      gender differences in some aspects of reproductive biology, such as internal
      female fertilization, the nature of these threats differs for men and women. Men,
      but not women, for example, have recurrently faced the problem of uncertainty in
      their genetic parenthood. Jealousy is an emotion hypothesized to have evolved to
      combat these threats. The 1992 article Sex Differences in Jealousy: Evolution,
      Physiology, and Psychology reported three empirical studies using two different
      methods, forced-choice and physiological experiments. Results supported the
      evolution-based hypotheses. The article became highly cited for several reasons.
      It elevated the status of jealousy as an important emotion to be explained by any
      comprehensive theory of human emotions. Subsequent meta-analyses robustly
      supported the evolutionary hypotheses. Moreover, the work supported the
      evolutionary meta-theory of gender differences, which posits differences only in
      domains in which the sexes have recurrently faced distinct adaptive problems. It
      also heralded the newly emerging field of evolutionary psychology as a useful
      perspective that possesses the scientific virtues of testability, falsifiability,
      and heuristic value in discovering previously unknown psychological phenomena.

PMID- 29592640
TI  - False-Positive Citations.
AB  - We describe why we wrote "False-Positive Psychology," analyze how it has been
      cited, and explain why the integrity of experimental psychology hinges on the
      full disclosure of methods, the sharing of materials and data, and, especially,
      the preregistration of analyses.

PMID- 29592641
TI  - Which Articles Make a Difference? Introduction to the Special 30th APS
      Anniversary Issue of Perspectives on Psychological Science.
AB  - This introduction to the special symposium on the top 30 most-cited articles in
      APS journals considers some of the factors that lead some articles to have huge
      impact. What is it that scientists can do to achieve the greatest impact for
      their work?

PMID- 29592642
TI  - Happiest People Revisited.
AB  - In a past Psychological Science article, Diener and Seligman (2002) explored the
      characteristics of extremely happy individuals and found that strong social
      relationships characterized the entire group. The study was popular, perhaps
      because the authors focused on the very happiest people, not merely on
      correlations across the entire spectrum of subjective well-being. In the current
      study, we replicated and extended the earlier paper here by examining, in a world
      sample, the differences between the happiest individuals and unhappy and
      averagely happy people. We largely replicated earlier findings; basic need
      fulfillment and social resources were two ingredients for high subjective well
      being. Replicating and extending the earlier findings, we found that, compared
      with the averagely happy people, the happiest people were more likely to come
      from societies high in subjective well-being and social capital. To achieve very
      high happiness, it is helpful not only to have desirable personal circumstances,
      but also to live in a prosperous happy society with strong social support. As in
      the original study, although a few characteristics seemed virtually necessary for
      subjective well-being (SWB), no characteristic guaranteed it. We also uncovered
      variables separating the groups that might be outcomes of SWB, for example,
      helping others, exercising, and not smoking.

PMID- 29592643
TI  - Reflections on Positive Emotions and Upward Spirals.
AB  - We reflect on our 2002 article and the impact this research report has had both
      within and beyond psychological science. This article was both one of the first
      publications to provide empirical support for hypotheses based on the broaden-and
      build theory of positive emotions and a product of the genesis of positive
      psychology. We highlight empirical and theoretical advancements in the scientific
      understanding of upward spiral dynamics associated with positive emotions, with
      particular focus on the new upward spiral theory of lifestyle change. We conclude
      by encouraging deeper and more rigorous tests of the prospective and reciprocal
      relations associated with positive emotions. Such progress is needed to better
      inform translations and applications to improve people's health and well-being.

PMID- 29592644
TI  - Well-Being With Soul: Science in Pursuit of Human Potential.
AB  - This essay examines core contributions of a model of psychological well-being
      that has had widespread scientific impact. It drew on distant formulations to
      identify new dimensions and measures for assessing what it means to be well. Key
      themes among the more than 750 studies using the model are sketched, followed by
      reflections about why there has been so much interest in this eudaimonic approach
      to well-being. A final section looks to the future, proposing new directions to
      illuminate the forces that work against the realization of human potential as
      well as those that nurture human flourishing and self-realization.

PMID- 29592645
TI  - Being Suspicious of the Sense of Ease and Undeterred by the Sense of Difficulty:
      Looking Back at Schmidt and Bjork (1992).
AB  - Richard Schmidt and I titled our article "New Conceptualizations of Practice:
      Common Principles in Three Paradigms Suggest New Concepts for Training" to
      reflect our view that prevailing ideas about how to optimize teaching, learning,
      and practicing were, in our words, "at best incomplete, and at worst incorrect."
      We argued that teachers and trainers were susceptible to being misled by two
      commonsense assumptions-namely, that procedures that enhance performance during
      training are the procedures of choice and that the context of training needs to
      match in detail the posttraining context that is the target of training. A
      variety of then-recent experimental findings challenged both assumptions and
      demonstrated, in particular, that procedures posing certain difficulties and
      appearing to slow the rate of learning often enhanced long-term retention and
      transfer of to-be-learned skills and knowledge. Given the parallel nature of such
      findings for both motor and verbal learning, we concluded that principles of
      considerable generality could be deduced to upgrade teaching and training.

PMID- 29592646
TI  - Beyond Money: Progress on an Economy of Well-Being.
AB  - In our 2004 "Beyond Money" article, we argued that national accounts of
      psychological and subjective well-being should complement the economic indicators
      that frequently guide policy decisions. We claimed that economic indicators fail
      to reflect important aspects of quality of life that well-being indicators
      capture. Since the time of our article, progress has been made, and scores of
      nations have used some forms of well-being measures. The National Academy of
      Sciences of the United States and the Organization for Economic Cooperation and
      Development both issued reports on accounts of well-being. Researchers have
      pointed to policies that are supported by the findings, such as environmental and
      economic policies. The emergence of "big data" has opened major new pathways for
      measuring well-being in inexpensive, unobtrusive, and nonreactive fashion.
      Psychological researchers now need to create superordinate combinations of
      subjective and objective measures of well-being to study the impact of the
      policies they advocate. The accounts can serve as a lever for convincing
      policymakers to enact policies that increase human flourishing.

PMID- 29592647
TI  - Reflections on the Resurgence of Interest in the Testing Effect.
AB  - We discuss the findings from our 2006 article in Psychological Science on the
      testing effect and describe how the project arose. The testing effect (or
      retrieval-practice effect) was first reported in the experimental literature
      about a century before our article was published, and the effect had been
      replicated (and sometimes discovered anew) many times over the years. Our
      experiments used prose materials (unlike most prior research) and produced a more
      powerful effect than prior research even though we used a conservative control
      condition for comparison. In our discussion, we drew out possible implications
      for educational practice. We also reported that students in the experiment could
      not predict the effect; this lack of metacognitive awareness represented a new
      finding in this context. In a companion article the same year, we provided an
      historical review of the testing effect. We believe the synergistic effect of the
      two articles accounts in part for the resurgence in interest in this phenomenon
      and its application in educational settings.

PMID- 29592648
TI  - Reflections on Self-Reflection: Contemplating Flawed Self-Judgments in the
      Clinic, Classroom, and Office Cubicle.
AB  - We reflect back on our 2004 monograph reviewing the implications of faulty self
      judgment for health, education, and the workplace. The review proved popular, no
      doubt because the importance of accurate self-assessment is best reflected in
      just how broad the literature is that touches on this topic. We discuss
      opportunities and challenges to be found in the future study of self-judgment
      accuracy and error, and suggest that designing interventions aimed at improving
      self-judgments may prove to be a worthwhile but complex and nuanced task.

PMID- 29592649
TI  - The Scientific Work We Love: A Duplex Theory of Scientific Impact and Its
      Application to the Top-Cited Articles in the First 30 Years of APS Journals.
AB  - This article proposes a duplex theory for understanding the scientific impact of
      contributions to psychological science. I argue that articles that we "love" can
      be understood in terms of (a) triangular elements of intimacy, passion, and
      commitment and (b) types of stories that characterize high-impact articles.
      Certain kinds of stories (e.g., review articles) are more likely to have lasting
      impact, on average, than other kinds of stories (e.g., data-driven empirical
      articles).

PMID- 29592650
TI  - Fitness Effects on the Cognitive Function of Older Adults: A Meta-Analytic Study
      Revisited.
AB  - We discuss the factors that encouraged us to examine the question of whether
      exercise training has a positive influence on cognitive health of older adults in
      2003. At that time there was a substantial literature on exercise and cognition.
      However, cognitive assessment instruments, exercise protocols (including type of
      exercise, length, and intensity of exercise programs), and subject-selection
      criteria differed widely. Our meta-analysis enabled us to examine both the main
      question under study-exercise effects on cognition-and potential moderators of
      this effect. Several interesting findings, which are briefly detailed in the
      present article, were revealed by our analyses. The current article also examines
      where the literature has gone since our 2003 article.

PMID- 29592651
TI  - The Scientific Pursuit of Happiness.
AB  - We review the history of happiness research that gave rise to our 1995 review. We
      then summarize-and update with a quick synopsis of more recent research-each of
      our conclusions regarding the associations of subjective well-being with age,
      gender, income, personal traits, social support, and religious engagement.
      Finally, we briefly review new research on the benefits of happiness, and of
      happiness interventions at both individual and national levels.

PMID- 29592652
TI  - The Strength Model of Self-Regulation: Conclusions From the Second Decade of
      Willpower Research.
AB  - The strength model of self-regulation uses a muscle analogy to explain patterns
      of ego depletion, conservation of willpower, and improved performance after
      frequent exercise. Our 2007 overview of the literature has been well cited,
      presumably because of the phenomenon's importance to theories of selfhood and a
      wide assortment of applied contexts, including problem behaviors. Some
      researchers have put forward rival theoretical accounts, and others have
      questioned the existence of the phenomenon. The weight of evidence continues to
      support the usefulness of the strength model, albeit amid continuing updates and
      revisions.

PMID- 29592653
TI  - The Constructive, Destructive, and Reconstructive Power of Social Norms: Reprise.
AB  - The influence of social norms on behavior has been a longstanding storyline
      within social psychology. Our 2007 Psychological Science publication presented a
      new rendition of this classic telling. The reported field experiment showed that
      social norms could be leveraged to promote residential energy conservation, but
      importantly, the descriptive norm was shown to increase consumption for low
      consuming households. This potential destructive effect of social norms was
      eliminated with the addition of an injunctive message of social approval for
      using less energy. The article is among the 30 most-cited articles across all APS
      publications, which we attribute to our methodology, which measured real behavior
      in a large-scale field experiment and to several circumstances associated with
      the timing of the work. The article coincided with the explosion of social media,
      the emergence of behavioral economics, and a heightened level of concern about
      climate change. These contemporaneous activities set the stage for our work and
      for its high degree of citation.

PMID- 29592654
TI  - Working Memory and Executive Attention: A Revisit.
AB  - In this follow-up to my 2002 article on working memory capacity, fluid
      intelligence, and executive attention in Current Directions in Psychological
      Science, I review even more evidence supporting the idea that the ability to
      control one's attention (i.e., executive attention) is important to working
      memory and fluid intelligence. I now argue that working memory tasks reflect
      primarily the maintenance of information, whereas fluid intelligence tests
      reflect primarily the ability to disengage from recently attended and no longer
      useful information. I also point out some conclusions in the 2002 article that
      now appear to be wrong.

PMID- 29592655
TI  - The Error-Related Negativity.
AB  - We look back on the events surrounding the genesis of our 1993 article on the
      error-related negativity (ERN), a component of the event-related brain potential
      that accompanies errors in the performance of speeded-response tasks. Our
      reminiscences focus on the personal friendships, intellectual influences, and
      chance occurrences that shaped the article. To put our work in historical
      context, we consider subsequent trends in neuroimaging, computational modeling,
      and psychiatry that gave the ERN high visibility and contributed to the longevity
      of its scientific interest.

PMID- 29592656
TI  - Revisiting "Most People Are Happy"-And Discovering When They Are Not.
AB  - In our 1996 article, "Most People are Happy," we presented evidence showing that
      the majority of humans are above neutral in happiness. The article was popular
      perhaps for several reasons. First, we shed light on the ubiquity of positive or
      pleasant emotions, whereas previously many scholars had focused on negative or
      unpleasant ones. Second, our article may have received attention because, as we
      showed, most people believe that humans are much less happy than they actually
      are. Thus, our article provided an impetus for understanding the role of positive
      emotions as well as illuminating an important aspect of human happiness-the fact
      that happiness is not unusual but may be the default condition. In the current
      article, we review evidence from the first representative sample of humanity, the
      Gallup World Poll, and include many more nations that are very poor and troubled.
      We find that the majority of people are above neutral in affect balance but not
      life satisfaction. Furthermore, there are extremely bad life circumstances in
      which most people are below neutral in affect balance as well. This suggests that
      one explanation for most people's happiness is that most societies, but not all,
      can meet enough human needs that they provide the conditions for human happiness.
      Finally, our findings suggest that human happiness is not just in our heads or
      genes but is also influenced by personal and societal circumstances.

PMID- 29592657
TI  - Toward a Psychology of Human Agency: Pathways and Reflections.
AB  - Social cognitive theory is founded on an agentic perspective. This article
      reviews the core features of human agency and the individual, proxy, and
      collective forms in which it is exercised. Agency operates through a triadic
      codetermination process of causation. Knowledge from this line of theorizing is
      widely applied to effect individual and social change, including worldwide
      applications that address some of the most urgent global problems.

PMID- 29592658
TI  - In Vitro Antibacterial Evaluation of Terminalia chebula as an Alternative of
      Antibiotics against Bovine Subclinical Mastitis.
AB  - The extent of subclinical mastitis in three breeds of cattle, Kankrej, Gir, and
      Crossbred, was performed at cattle farms in Anand town of Gujarat State, India.
      The prevalence of subclinical mastitis in crossbred cattle was higher compared to
      local breed of cattle. Causative agents identified using 16S rDNA polymerase
      chain reaction (PCR)-based molecular method were Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa, and Bacillus megaterium. In vitro
      antibacterial activity of ethyl acetate extract of plant Terminalia chebula
      (Combretaceae) was checked by agar well diffusion method against four isolated
      and molecularly identified microorganisms. Ethyl acetate extract shows
      antimicrobial activity with varying magnitudes against all identified isolates.
      Among the three different concentrations, 500 ug/mL conc. of extract is as
      effective as that of standard amoxicillin. In vitro results support the use of
      plant extract from T. chebula as an alternative to antibiotics therapy against
      bovine subclinical mastitis.

PMID- 29592765
TI  - Alternative surgical procedure for treating superior vena cava syndrome in a
      hemodialysis patient.
AB  - BACKGROUND: The incidence of superior vena cava syndrome has been increasing in
      hemodialysis patients with the widespread use of dialysis catheters. Although
      endovascular intervention remains the primary choice for treatment, the long-term
      patency rate is not optimistic. Occlusive lesions are often encountered that
      cannot be opened using this intervention. Therefore, we chose to present this
      case involving a pericardial patch used to reconstruct the superior vena cava in
      the treatment of catheter-associated chronic superior vena cava occlusion.
      METHODS: Here, we report a case of facial swelling and severe bilateral pleural
      effusion secondary to superior vena cava occlusion in a 41-year-old woman. An
      endovascular venous intervention was attempted initially but failed. Finally, we
      adopted a procedure using the pericardium as a patch to reconstruct the superior
      vena cava, maintaining most of the original anatomical structure. RESULTS: This
      patient's facial swelling and bilateral pleural effusion disappeared after the
      operation. In addition, her symptoms of coughing and dyspnea were relieved. The
      Brescia-Cimino fistula in her left forearm functioned well. CONCLUSION: The use
      of a pericardial patch to reconstruct the superior vena cava is a reliable
      approach in patients who are not candidates for endovascular treatment.

PMID- 29592766
TI  - Surface contamination of counting tools after mock dispensing of cyclophosphamide
      in a simulated outpatient pharmacy.
AB  - PURPOSE: The primary aim was to determine if dispensing of cyclophosphamide
      tablets resulted in accumulated residue on pharmacy counting tools during a
      simulated outpatient dispensing process. Secondary objectives included
      determining if cyclophosphamide contamination exceeded a defined threshold level
      of 1 ng/cm2 and if a larger number of prescriptions dispensed resulted in
      increased contamination. METHODS: Mock prescriptions of 40 cyclophosphamide 50 mg
      tablets were counted on clean trays in three scenarios using a simulated
      outpatient pharmacy after assaying five cleaned trays as controls. The three
      scenarios consisted of five simulated dispensings of one, three, or six
      prescriptions dispensed per scenario. Wipe samples of trays and spatulas were
      collected and assayed for all trays, including the five clean trays used as
      controls. Contamination was defined as an assayed cyclophosphamide level at or
      above 0.001 ng/cm2 and levels above 1 ng/cm2 were considered sufficient to cause
      risk of human uptake. Mean contamination for each scenario was calculated and
      compared using one-way analysis of variance. P-values of < 0.05 implied
      significance. RESULTS: Mean cyclophosphamide contamination on trays used to count
      one, three, and six cyclophosphamide prescriptions was 0.51 +/- 0.10 (p=0.0003),
      1.02 +/- 0.10 (p < 0.0001), and 1.82 +/- 0.10 ng/cm2 (p < 0.0001), respectively.
      Control trays did not show detectable cyclophosphamide contamination. Increasing
      the number of prescriptions dispensed from 1 to 3, 1 to 6, and 3 to 6 counts
      increased contamination by 0.51 +/- 0.15 (p = 0.0140), 1.31 + 0.15 (p < 0.0001),
      and 0.80 +/- 0.15 ng/cm2 (p = 0.0004), respectively. CONCLUSION: Dispensing one
      or more prescriptions of 40 cyclophosphamide 50 mg tablets contaminates pharmacy
      counting tools, and an increased number of prescriptions dispensed correlates
      with increased level of contamination. Counting out three or more prescriptions
      leads to trays having contamination that surpasses the threshold at which worker
      exposure may be increased. Pharmacies should consider devoting a separate tray to
      cyclophosphamide tablets, as cross-contamination could occur with other drugs and
      the efficacy of decontamination methods is unclear. Employee exposure could be
      minimized with the use of personal protective equipment, environmental controls,
      and cleaning trays between uses. Future investigation should assess the extent of
      drug powder dispersion, the effects of various cleaning methods, and the
      potential extent of contamination with different oral cytotoxic drugs.

PMID- 29592767
TI  - Drug shortages in a pediatric stem cell transplantation ward: Challenges and
      implications. A 5-year bilan.
AB  - This article describes the implications of shortages of pharmaceutical products
      used in conditioning and supportive care regimens of pediatric patients
      undergoing a hematopoietic stem cell transplantation in a tertiary care hospital.
      Between July 2011 and July 2016, a total of 84 individual shortages, affecting 22
      different drugs (79.8% supportive care drugs; 20.2% chemotherapeutics) were
      detected with a mean duration of 85 days (SD 138) per individual drug shortage.
      Eighteen shortages were critical and very urgent. Sulfamethoxazol/trimethoprim,
      piperacillin/tazobactam, ranitidine, benzylpenicillin, ondansetron (supportive
      care) and methotrexate, melphalan (chemotherapeutics) had the longest supply
      disruptions. A variety of solutions could be identified including the purchase of
      a generic alternative (36.9%) for both oral and parenteral treatments (in a ratio
      3:2). Urgent import from another (European) country was performed in 14 cases
      (16.7%). High impact solutions such as cohorting of patients and change of
      ongoing treatments (2.4%) were used for parenteral treatments only.
      Pharmaceutical modification was sometimes applied for oral treatments (2.4%). Due
      to persistent occurrence of these shortages, an efficient pharmacy workflow
      (electronic follow-up by end of 2016) and a multidisciplinary approach were
      needed.

PMID- 29592768
TI  - Effect of deformation history on the stress relaxation behaviour of Colombian
      Caribbean coastal cheese from goat milk.
AB  - Textural attributes are a manifestation of the rheological properties and
      physical structure of foods, cheeses among these. In order to describe these
      physical properties, the objective of this work was to analyse the effect of
      deformation history on the stress relaxation behaviour of Colombian Caribbean
      coastal cheese made from goat milk with 3.75% (F1), 4.00% (F2) and 4.25% (F3) fat
      content, through prediction made by a four-term Prony series based on Chen's
      model. For this, stress relaxation data and stress relaxation spectra were
      analysed. Moreover, textural attributes by texture profile analysis were
      measured. Physicochemical results were similar to those published by other
      authors, and all samples meet national and international standards. Results from
      this work showed that Chen's model could be successfully used to describe the
      effect of deformation history on the stress relaxation behaviour of Colombian
      Caribbean coastal cheese made from goat milk. F1 had the highest elastic
      response, with the most significant residual modules ( P0) and relaxation times
      (tau1, tau2 and tau3). On the other hand, residual modules and relaxation times
      (tau1, tau2 and tau3) for cheeses F2 and F3 did not present statistically
      significant differences (p > 0.05). Besides, by interpretation of the stress
      relaxation spectra, F1 presented the firmest structure (greatest distribution
      function and relaxation time) which was characterised by the highest elastic
      behaviour. Finally, according to texture profile analysis test, F1 had the
      highest hardness, cohesiveness and chewiness, whereas F2 and F3 did not present
      statistically significant differences (p > 0.05) between them.

PMID- 29592769
TI  - All trans retinoic acid modulates TNF-alpha and CYP2E1 pathways and enhances
      regression of ethanol-induced fibrosis markers in hepatocytes and HSCs in
      abstaining rodent model.
AB  - CONTEXT: Our previous studies showed that all trans retinoic acid (ATRA)
      ameliorates alcohol-induced toxicity. Hence, we evaluated the efficacy of ATRA
      and abstention in the regression of alcohol-induced hepatotoxicity. MATERIALS AND
      METHODS: After ethanol administration to rats for 90 days, the regression of
      alcohol-induced toxicity was studied by supplementing ATRA at a dose of 100
      MUg/kg body weight for 30 days. It was also compared with animals in abstention.
      RESULTS AND DISCUSSION: Ethanol administration enhanced oxidative stress,
      activated HSCs and increased collagen deposition. All these alterations were
      reversed to a certain extent by ATRA supplementation. CONCLUSIONS: ATRA had
      better efficacy than just abstention in reducing ethanol-induced toxicity. The
      mechanism might be downregulation of CYP2E1, leading to reduced oxidative stress
      in the hepatocytes and thus impeding NFkappaB activation, cytokine production,
      activation of HSC and resulting in the reduction of inflammation and remodelling
      of fibrosis by modulating MMP and TIMP.

PMID- 29592770
TI  - Using Systems Theory to Examine Patient and Nurse Structures, Processes, and
      Outcomes in Centralized and Decentralized Units.
AB  - OBJECTIVES: This study utilizes systems theory to understand how changes to
      physical design structures impact communication processes and patient and staff
      design-related outcomes. BACKGROUND: Many scholars and researchers have noted the
      importance of communication and teamwork for patient care quality. Few studies
      have examined changes to nursing station design within a systems theory
      framework. METHOD: This study employed a multimethod, before-and-after, quasi
      experimental research design. Nurses completed surveys in centralized units and
      later in decentralized units ( N = 26pre, N = 51post). Patients completed surveys
      ( N = 62pre) in centralized units and later in decentralized units ( N = 49post).
      Surveys included quantitative measures and qualitative open-ended responses.
      RESULTS: Patients preferred the decentralized units because of larger single
      occupancy rooms, greater privacy/confidentiality, and overall satisfaction with
      design. Nurses had a more complex response. Nurses approved the patient rooms,
      unit environment, and noise levels in decentralized units. However, they reported
      reduced access to support spaces, lower levels of team/mentoring communication,
      and less satisfaction with design than in centralized units. Qualitative findings
      supported these results. Nurses were more positive about centralized units and
      patients were more positive toward decentralized units. CONCLUSION: The results
      of this study suggest a need to understand how system components operate in
      concert. A major contribution of this study is the inclusion of patient
      satisfaction with design, an important yet overlooked fact in patient
      satisfaction. Healthcare design researchers and practitioners may consider how
      changing system interdependencies can lead to unexpected changes to communication
      processes and system outcomes in complex systems.

PMID- 29592772
TI  - To Grow as a Physician, Try Responding to Suffering.

PMID- 29592771
TI  - Top Five Physical Design Factors Contributing to Fall Initiation.
AB  - PURPOSE:: To develop a prioritized list of physical design
      questions/interventions to reduce patient falls by conducting expanded analysis
      (Phase II) of data generated from a completed study phase. BACKGROUND:: Patient
      falls continue to be a critical concern for healthcare providers, patients, and
      families. While substantial literature exist on intrinsic factors, scientific
      evidence on the role of the physical environment is scarce. METHOD:: Expanded
      analysis of data from 180 videos of trials conducted in a physical mock-up of a
      medical-surgical inpatient room in a previously completed study phase. The odds
      of subject's exhibited postures (predictors) on fall initiation (outcome) were
      examined in a series of generalized linear mixed effects models. Physical design
      elements and attributes associated with postures exhibiting statistical
      significance were examined. RESULTS:: Turning, pulling, pushing, and bending
      forward exhibited the highest odds of contributing to fall initiation in the
      bathroom. Grabbing, pushing, and sitting exhibited the highest odds of
      contributing to fall initiation around the patient bed. Physical design
      elements/attributes associated with the above postures are the (1) bathroom door;
      (2) bathroom spatial configuration-relative locations of door, toilet bowl, and
      the sink; (3) door, toilet, and sink hardware; (4) space availability/tightness
      inside the clinician zone; and (5) spatial configuration around patient bed
      relative locations of bed, patient chair, and overbed table, in relation to
      bathroom door, and resulting obstructions originating from the configuration.
      CONCLUSIONS:: Patient falls during unassisted ambulation may be reduced through
      appropriate examination of these five physical elements/attributes.

PMID- 29592773
TI  - Effect of changing from preserved prostaglandins to preservative-free tafluprost
      in patients with glaucoma on tear film thickness.
AB  - PURPOSE: Long-term glaucoma therapy with preservative-containing eye drops may
      impact ocular surface health. This study was performed to investigate whether a
      switch from preserved topical prostaglandin therapy to preservative-free
      tafluprost therapy improves precorneal tear film thickness in patients with
      glaucoma or ocular hypertension. METHODS: A total of 30 patients who were under
      topical preservative-containing prostaglandin monotherapy for at least 6 months
      were included. Patients were then switched from preserved prostaglandin therapy
      to unpreserved tafluprost drops once daily. Tear film thickness was measured at
      baseline and 4 and 12 weeks after therapy change with an ultrahigh-resolution
      optical coherence tomography system. Furthermore, clinical measures of ocular
      surface disease were determined and symptoms were assessed using the Dry Eye
      Related Quality-of-Life Score. RESULTS: After switching to unpreserved
      tafluprost, tear film thickness significantly increased from 4.7 +/- 0.5 to 5.0
      +/- 0.6 um 4 weeks after therapy change and still tended to be increased after 12
      weeks (4.8 +/- 0.7 um). Breakup time significantly increased from 5.1 +/- 2.3 to
      7.2 +/- 3.4 s and to 10.1 +/- 3.6 s after therapy change. In addition, a
      significant decrease in corneal staining score from 1.8 +/- 0.7 to 1.4 +/- 0.8
      after 4 weeks and to 0.7 +/- 0.7 after 12 weeks treatment was observed. Switching
      to preservative-free drops reduced Dry Eye-Related Quality-of-Life Score from
      11.4 +/- 11.0 to 5.7 +/- 6.4 and to 4.7 +/- 7.5. CONCLUSION: Our data show that
      switching to preservative-free tafluprost leads to an increase in tear film
      thickness, breakup time, and an improvement of Dry Eye-Related Quality-of-Life
      Score. Our results therefore indicate that a switch to unpreserved tafluprost is
      beneficial for ocular surface health in patients under long-term preserved
      prostaglandin eye drops.

PMID- 29592774
TI  - A Validation Study of the Child Pornography Offender Risk Tool (CPORT).
AB  - The Child Pornography Offender Risk Tool (CPORT) is a seven-item structured tool
      to assess the likelihood of future sexual offending over a 5-year fixed follow
      up. The current study examined 5-year fixed follow-up data (15% any new sexual
      offense, 9% any new child pornography offense) for a validation sample of 80 men
      convicted of child pornography offense(s). Although statistical power was low,
      results were comparable with the development sample: The CPORT had slightly lower
      predictive accuracy for sexual recidivism for the overall group (area under the
      curve [AUC] = .70 vs. .74), but these values were not significantly different.
      Combining the development and validation samples, the CPORT predicted any sexual
      recidivism (AUC = .72) and child pornography recidivism specifically (AUC = .74),
      with similar accuracies. CPORT was also significantly predictive of these
      outcomes for the child pornography offenders with no known contact offenses.
      Strengths and weaknesses of incorporating CPORT into applied risk assessments are
      discussed.

PMID- 29592775
TI  - Macrophage Migration Inhibitory Factor Receptor, CD74, is Overexpressed in Human
      and Baboon ( Papio Anubis) Endometriotic Lesions and Modulates Endometriotic
      Epithelial Cell Survival and Interleukin 8 Expression.
AB  - CD74 is the primary receptor for macrophage migration inhibitory factor (MIF).
      Although expression of MIF has been described in endometriotic lesions, the
      cellular localization and function of the MIF receptor, CD74, are poorly
      understood. To further explore the role of CD74 in the pathophysiology of
      endometriosis, we utilized specimens from women with diagnostically confirmed
      endometriosis, women with no signs or symptoms of endometriosis (controls), and 8
      baboons with experimentally induced endometriosis. Compared to eutopic
      endometrium from women with endometriosis, CD74 transcript expression was
      significantly increased in endometriotic lesion tissue. Similarly, cellular
      expression of CD74 was significantly greater in ectopic lesion tissue compared to
      paired eutopic endometrium, which both expressed greater CD74 expression compared
      to eutopic endometrium from control patients. Localization of CD74 was
      predominant to epithelial cells of ectopic and matched eutopic endometrium and
      was not influenced by the stage of the menstrual cycle. Eutopic endometrium from
      control patients did not express detectable levels of CD74 protein by
      immunohistochemistry. This pattern of expression and CD74 protein localization
      could be recapitulated in endometriotic lesion tissue from baboons with
      experimentally induced disease. Transfection of the endometriotic epithelial cell
      lines, 12Z with CD74 short hairpin RNA (shRNA), resulted in a significant
      decrease in CD74 protein expression, which was associated with a significant
      reduction in cellular proliferation as well as the expression of the prosurvival
      cytokine interleukin 8. Together, these data support the hypothesis that CD74 is
      elevated in endometriotic lesion tissue and may contribute to the pathogenesis of
      endometriosis by promoting cell survival.

PMID- 29592776
TI  - Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis.
AB  - Endometriosis, which has been considered an epigenetic disease, is a prevalent
      gynecological disorder worldwide. With an emphasis on changes in the HOXA10 gene
      expression of the endometrium of women with endometriosis, the aim of this study
      was to investigate HOXA10 gene expression and its correlation with the epigenetic
      characteristics of the specific promoter region of the gene in the eutopic and
      ectopic endometrium of women with endometriosis. Thirty-six patients and 21
      healthy fertile women were recruited as participants of this study. In this study
      group, chromatin immunoprecipitation and real-time polymerase chain reaction
      technique were performed to quantify the epigenetic profile of HOXA10, parallel
      to its expression. During the secretory phase in eutopic tissues, reduction in
      HOXA10 gene expression was identified along with lower acetylation and higher
      methylation of H3K9 as well as higher incorporation of MeCP2 on the HOXA10 gene
      promoter. In contrast with control group, studies of ectopic endometriotic
      lesions in the secretory phase demonstrate a correlation between induction of
      HOXA10 gene and higher levels of H3K9ac, H3K27me3, and H3K4me3 in the promoter
      region of the HOXA10 gene. Further distinctions from the control group were
      revealed in the proliferative phase of the ectopic endometrium, where
      upregulation of HOXA10 coincided with lower incorporation of MeCP2 and higher
      levels of H3K4me3 in the promoter region. Since it is well known that aberrant
      expression of HOXA10 is involved in pathogenesis of the endometrium, our data
      emphasized the epigenetic role of this gene aberration related to clinical
      pathophysiology of endometriosis.

PMID- 29592777
TI  - An intraocular micro light-emitting diode device for endo-illumination during
      pars plana vitrectomy.
AB  - PURPOSE: Development of a new, fiber-free, single-use endo-illuminator for pars
      plana vitrectomy as a replacement for fiber-based systems with external light
      sources. The hand-guided intraocularly placed white micro light-emitting diode is
      evaluated for its illumination properties and potential photochemical and thermal
      hazards. METHODS: A micro light-emitting diode was used to develop a single-use
      intraocular illumination system. The light-source-on-tip device was implemented
      in a prototype with 23G trocar compatible outer diameter of 0.6 mm. The
      experimental testing was performed on porcine eyes. All calculations of possible
      photochemical and thermal hazards during the application of the intraocular micro
      light-emitting diode were calculated according to DIN EN ISO 15007-2: 2014.
      RESULTS: The endo-illuminator generated a homogeneous and bright illumination of
      the intraocular space. The color impression was physiologic and natural. Contrary
      to initial apprehension, the possible risk caused by inserting a light-emitting
      diode into the intraocular vitreous was much smaller when compared to
      conventional fiber-based illumination systems. The photochemical and thermal
      hazards allowed a continuous exposure time to the retina of at least 4.7 h.
      CONCLUSION: This first intraocular light source showed that a light-emitting
      diode can be introduced into the eye. The system can be built as single-use
      illumination system. This light-source-on-tip light-emitting diode-endo
      illumination combines a chandelier wide-angle illumination with an adjustable
      endo-illuminator.

PMID- 29592778
TI  - Posterior reversible encephalopathy syndrome in HIV-positive patients: a case
      report and literature review.
AB  - We are reporting the case of a woman who was admitted acutely to our intensive
      care unit without any collateral history. She was diagnosed with posterior
      reversible encephalopathy syndrome (PRES) as a consequence of poor adherence to
      anti-hypertensive, anti-diabetic and anti-retroviral medications. PRES is a rare
      condition, which may cause cortical blindness; contrary to its name it is not
      always reversible. Rapid diagnosis and aggressive management of underlying causes
      facilitate reversibility of PRES. We also summarise the literature on patients
      with HIV and PRES.

PMID- 29592779
TI  - Associations of Urinary Cotinine-Verified Active and Passive Smoking with Thyroid
      Function: Analysis of Population-Based Nationally Representative Data.
AB  - BACKGROUND: The effects of active and passive smoking on thyroid function in the
      Korean population have not been determined. Furthermore, related research is
      based on self-reported smoking status, which may be inaccurate, especially among
      women. The present study aimed at evaluating the association between
      biochemically verified smoking status and thyroid function in a nationally
      representative Korean population. METHODS: This population-based cross-sectional
      study included 3404 subjects without thyroid disease who were not taking thyroid
      medication. Smoking status was identified using self-reported data and urinary
      cotinine levels. Kruskal-Wallis and Jonckheere-Terpstra trend tests were
      performed to evaluate the association between smoking exposure and thyroid
      function. Multivariate logistic regression analysis was used to estimate the
      effect of smoking on subclinical hypothyroidism (SCH). RESULTS: Biochemically
      verified active and passive smoking rates were 43.4% and 23.3% among men and
      10.0% and 22.9% among women, respectively. Active smokers had significantly lower
      iodine levels than passive smokers and nonsmokers. Active smoking was associated
      with decreased serum thyrotropin (TSH) levels among both sexes, although only men
      exhibited a dose-response relationship between increasing smoking exposure and
      decreasing TSH levels. Passive smoking slightly decreased TSH levels, but the
      decrease was not statistically significant. The risk of SCH decreased with
      increasing smoking exposure in the multivariate-adjusted analysis (p for trend =
      0.027 among men and 0.042 among women). CONCLUSIONS: Active and passive smoking
      were associated with decreasing serum TSH levels and a lower risk of SCH in a
      Korean population. These associations might be related to lower urinary iodine
      levels in active smokers.

PMID- 29592780
TI  - Downregulation of neuroligin1 ameliorates postoperative pain through inhibiting
      neuroligin1/postsynaptic density 95-mediated synaptic targeting of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate receptor GluA1 subunits in rat dorsal
      horns.
AB  - Neuroligin1 is an important synaptic cell adhesion molecule that modulates the
      function of synapses through protein-protein interactions. Yet, it remains
      unclear whether the regulation of synaptic transmission in the spinal cord by
      neruoligin1 contributes to the development of postoperative pain. In a rat model
      of postoperative pain induced by plantar incision, we conducted Western blot
      study to examine changes in the expression of postsynaptic membrane of
      neuroligin1, postsynaptic density 95 (PSD-95), and alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionate (AMPA) receptor GluA1 and GluA2 subunits in the spinal
      cord dorsal horn after injury. The interaction between neuroligin1 and PSD-95 was
      further determined by using coimmunoprecipitation. Protein levels of neuroligin1
      and GluA1, but not GluA2 and PSD-95, were significantly increased in the
      postsynaptic membrane of the ipsilateral dorsal horn at 3 h and 1 day after
      incision, as compared to that in control group (naive). A greater amount of PSD
      95 was coimmunoprecipitated with neuroligin1 at 3 h after incision than that in
      the control group. Intrathecal administration of small interfering RNAs (siRNAs)
      targeting neuroligin1 suppressed the expression of neuroligin1 in the spinal
      cord. Importantly, pretreatment with intrathecal neuroligin1 siRNA2497, but not
      scrambled siRNA or vehicle, prevented the upregulation of GluA1 expression at 3 h
      after incision, inhibited the enhanced neuroligin1/PSD-95 interaction, and
      attenuated postoperative pain. Together, current findings suggest that
      downregulation of spinal neuroligin1 expression may ameliorate postoperative pain
      through inhibiting neuroligin1/PSD-95 interaction and synaptic targeting of GluA1
      subunit. Accordingly, spinal neuroligin1 may be a potential new target for
      postoperative pain treatment.

PMID- 29592781
TI  - No requirement of interlukine-1 for long-term potentiation in the anterior
      cingulate cortex of adult mice.
AB  - : Background The enhanced expression of cytokines in the pathological states
      suggests that they have important roles in the initiation or maintenance of
      disease states. FINDINGS: To determine the involvement of cytokines in chronic
      neuropathic pain, the expression of cytokines in the anterior cingulate cortex
      neurons in the ligation of the common peroneal nerve mice was investigated. We
      utilized a cytokine enzyme-linked immunosorbent assay plate array to detect 23
      cytokines in total eight mice including a female, and no significant differences
      were found in those cytokines between the common peroneal nerve model and sham
      surgery mice. Quantification of TNF-alpha at protein level revealed the unvaried
      expression in the anterior cingulate cortex in both neuropathic pain and visceral
      pain, but enhanced expression in the insular cortex in the visceral pain.
      Furthermore, we found that the IL-Ira, a kind of IL-1 receptor antagonist, had no
      effect on the theta burst stimulation-induced long-term potentiation in the
      anterior cingulate cortex. Conclusions Cytokines are not involved in chronic
      neuropathic pain induced by nerve injury in the anterior cingulate cortex. Our
      findings suggested that cytokines may not be a viable drug target to treat
      chronic neuropathic pain in the anterior cingulate cortex.

PMID- 29592782
TI  - Resveratrol enhances IL-4 receptor-mediated anti-inflammatory effects in spinal
      cord and attenuates neuropathic pain following sciatic nerve injury.
AB  - Resveratrol has been showed to relieve neuropathic pain through its anti
      inflammatory effects on the peripheral nerve system. However, it is not clear
      whether resveratrol, especially when administered systemically, is effective in
      alleviating the peripheral neuropathy-induced imbalance between pro- and anti
      inflammatory responses in the central nervous system. To test this, we used a rat
      neuropathic pain model resulting from chronic constriction injury of the sciatic
      nerve. Resveratrol (200 mg/kg) or vehicle (dimethylsulfoxide) were administered
      intraperitoneally once daily for 14 consecutive days after chronic constriction
      injury. We found that resveratrol attenuated mechanical allodynia and thermal
      hyperalgesia in rats with chronic constriction injury. After 14 days of
      resveratrol treatment, expression of several anti-inflammatory cytokine
      receptors, including IL-1RA and IL-1R2, was increased in the dorsal spinal cord
      of rats with chronic constriction injury, and IL-4Ralpha was increased in dorsal
      spinal cord neurons. Knockdown of IL-4Ralpha in a neuronal cell line reversed the
      resveratrol-induced upregulation of IL-1RA and IL-1R2. These results indicate
      that resveratrol enhances IL-4 receptor-mediated anti-inflammatory responses in
      the spinal cord and thus might contribute to the alleviation of central
      sensitization following peripheral nerve injury.

PMID- 29592783
TI  - Synergistic activation of ERK1/2 between A-fiber neurons and glial cells in the
      DRG contributes to pain hypersensitivity after tissue injury.
AB  - Background Intense nociceptive signaling arising from ongoing injury activates
      primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2
      phosphorylation in dorsal root ganglion can be used to visualize intracellular
      signal activity immediately after noxious stimulation. The aim of this study was
      to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against
      tissue injury in the primary afferent neurons. Methods Plantar incisions were
      made in the hind paws of Sprague-Dawley rats (n =150). Levobupivacaine was
      injected into the plantar aspect of the paws and ankles, Mitogen-activated
      protein kinase kinase (MEK) inhibitor was injected into the paw, and
      carbenoxolone, dual inhibitor of the gap junction and pannexin channel, was
      intraperitoneally injected. Pain hypersensitivity was investigated by a
      behavioral study, while phosphorylated ERK1/2 was detected in dorsal root
      ganglion and hind paw using immunohistochemistry and Western blot. Results
      Phosphorylated ERK1/2 was induced in dorsal root ganglion (26.8 +/- 2.9% at
      baseline, 65.6 +/- 3.6% at 2 min, and 26.3 +/- 3.4% at 2 h) after the incision.
      NF-200 positive A-fiber neurons and satellite glial cells were positive for
      phosphorylated ERK1/2. Injury-induced pain hypersensitivity was abolished by MEK
      inhibitor. Levobupivacaine treatment inhibited phosphorylated ERK1/2 induction,
      carbenoxolone treatment inhibited glial phosphorylated ERK1/2 at 2 min after the
      injury, and carbenoxolone inhibited pain hypersensitivity and neuronal
      phosphorylated ERK1/2 at 1 h after the injury. Conclusion ERK1/2 phosphorylation
      in A-fiber neurons and satellite glial cells immediately after injury contributes
      to the generation of pain hypersensitivity. Signal communication between neurons
      and satellite glial cells expands the duration of neuronal ERK1/2 phosphorylation
      and pain hypersensitivity at 1 h after tissue injury.

PMID- 29592784
TI  - The analgesic effect of early hyperbaric oxygen treatment in chronic constriction
      injury rats and its influence on nNOS and iNOS expression and inflammatory factor
      production.
AB  - Objective To observe the analgesic effect of early hyperbaric oxygen (HBO)
      treatment in chronic constriction injury (CCI) rats, and to analyze the influence
      of HBO on the expression of neuronal nitric oxide synthase and inducible nitric
      oxide synthase and on the levels of inflammatory factors. Methods Rats were
      assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model
      was established, and HBO treatment at 2.5 ATA (60 min) was given one day after
      surgery, lasting for five consecutive days. The pain behaviors of the rats were
      observed at predetermined time points, and the activation of astrocytes at dorsal
      horns as well as the changes of the synaptic ultrastructures were observed. The
      expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase
      were detected by Western blot, and the levels of tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1 beta (IL-1beta) were detected by quantitative real-time
      PCR. Results Rats in the CCI group developed hyperalgesia when compared with the
      sham group. Mechanical withdrawal threshold decreased and thermal withdrawal
      latency shortened in CCI group. Also, astrocytes at the dorsal horn were
      activated, the synaptic structure was disordered, the expressions of inducible
      nitric oxide synthase and neuronal nitric oxide synthase were increased
      significantly, and the release of inflammatory factor (TNF-alpha and IL-1beta)
      was up-regulated. However, with early initiation of HBO treatment, rats in the
      HBO group showed significantly alleviated hyperalgesia, increased mechanical
      withdrawal threshold, and prolonged thermal withdrawal latency. HBO treatment
      inhibited astrocyte expression and maintained normal synaptic structure. The
      expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase
      were decreased in the dorsal horn, and the release of inflammatory factor (TNF
      alpha and IL-1beta) was reduced. Conclusions Early HBO treatment significantly
      improves hyperalgesia in rats with neuropathic pain. The decreased expressions of
      inducible nitric oxide synthase and neuronal nitric oxide synthase and reduced
      levels of inflammatory factors are important mechanisms by which early HBO helps
      to alleviate neuropathic pain.

PMID- 29592787
TI  - Theoretical underpinnings of state institutionalisation of inclusion and
      struggles in collective health in Latin America.
AB  - Community participation as a strategy in health aims to increase the role of
      citizens in health decision-making which are contextualised within the
      institutions of democracy. Electoral representation as the dominant model of
      democracy globally is based on the elite theory of democracy that sees political
      decision-making a prerogative of political elites. Such political elitism is
      counter to the idea of democratic participation. Neoliberalism together with
      elitism in political sphere have worsened social inequities by undermining
      working class interests. Latin America has seen adverse consequences of these
      social inequities. In response, social movements representing collective
      struggles of organised citizens arose in the region. This paper explores the
      theoretical underpinnings of democratic participation in contemporary Latin
      American context at the nexus of emerging social movement activism and policy
      responses. The paper will use empirical examples to highlight how such democratic
      practices at the societal level evolved while demanding political inclusion.
      These societal democratic practices in Latin America are redefining democracy,
      which continues to be seen in the political sphere only. Health reforms promoting
      participatory democracy in several Latin American countries have demonstrated
      that establishing institutions and mechanisms of democratic participation
      facilitate collective participation by the organised citizenry in state affairs.

PMID- 29592785
TI  - Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons
      contributes to neuropathic pain in rats with spared nerve injury.
AB  - Ion channels are very important in the peripheral sensitization in neuropathic
      pain. Our present study aims to investigate the possible contribution of CaV3.2 T
      type calcium channels in damaged dorsal root ganglion neurons in neuropathic
      pain. We established a neuropathic pain model of rats with spared nerve injury.
      In these model rats, it was easy to distinguish damaged dorsal root ganglion
      neurons (of tibial nerve and common peroneal nerve) from intact dorsal root
      ganglion neurons (of sural nerves). Our results showed that CaV3.2 protein
      expression increased in medium-sized neurons from the damaged dorsal root
      ganglions but not in the intact ones. With whole cell patch clamp recording
      technique, it was found that after-depolarizing amplitudes of the damaged medium
      sized dorsal root ganglion neurons increased significantly at membrane potentials
      of -85 mV and -95 mV. These results indicate a functional up-regulation of CaV3.2
      T-type calcium channels in the damaged medium-sized neurons after spared nerve
      injury. Behaviorally, blockade of CaV3.2 with antisense oligodeoxynucleotides
      could significantly reverse mechanical allodynia. These results suggest that
      CaV3.2 T-type calcium channels in damaged medium-sized dorsal root ganglion
      neurons might contribute to neuropathic pain after peripheral nerve injury.

PMID- 29592788
TI  - Model-Based Demography: Essays on Integrating Data, Technique and Theory.

PMID- 29592786
TI  - Attenuation of offset analgesia is associated with suppression of descending pain
      modulatory and reward systems in patients with chronic pain.
AB  - Background Offset analgesia is a disproportionate decrease of pain perception
      following a slight decrease of noxious thermal stimulus and attenuated in
      patients with neuropathic pain. We examined offset analgesia in patients with
      heterogeneous chronic pain disorders and used functional magnetic resonance
      imaging to explore modification of cerebral analgesic responses in comparison
      with healthy controls. Results We recruited seventeen patients with chronic pain
      and seventeen age-, sex-matched healthy controls. We gave a noxious thermal
      stimulation paradigm including offset analgesia and control stimuli on the left
      volar forearm, while we obtained a real-time continuous pain rating and a whole
      brain functional magnetic resonance imaging. Baseline, first plateau (5 s),
      increment (5 s), and second plateau (20 s) temperatures of offset analgesia
      stimulus were set at 32 degrees C, 46 degrees C, 47 degrees C, and 46 degrees C,
      respectively. Control stimulus included 30-s 46 degrees C stimulus or only the
      first 10 s of offset analgesia stimulus. We evaluated magnitude of offset
      analgesia, analyzed cerebral activation by thermal stimulation, and further
      compared offset analgesia-related activation between the groups. Magnitude of
      offset analgesia was larger in controls than in patients (median: 28.9%
      (interquartile range: 11.0-56.0%) vs. 19.0% (4.2-48.7%), p = 0.047). During the
      second plateau, controls showed a larger blood oxygenation level-dependent
      activation than patients at the putamen, anterior cingulate, dorsolateral
      prefrontal cortices, nucleus accumbens, brainstem, and medial prefrontal cortex (
      p < 0.05), which are known to mediate either of descending pain modulation or
      reward responses. Offset analgesia-related activity at the anterior cingulate
      cortex was negatively correlated with neuropathic component of pain in patients
      with chronic pain ( p = 0.004). Conclusions Attenuation of offset analgesia was
      associated with suppressed activation of the descending pain modulatory and
      reward systems in patients with chronic pain, at least in the studied cohort. The
      present findings might implicate both behavioral and cerebral plastic alterations
      contributing to chronification of pain. Clinical trial registry: The Japanese
      clinical trials registry (UMIN-CTR, No. UMIN000011253; http://www.umin.ac.jp/ctr
      /).

PMID- 29592789
TI  - Erratum.

PMID- 29592791
TI  - Gene Therapy Now?

PMID- 29592790
TI  - Retraction.

PMID- 29592792
TI  - Retraction.

PMID- 29592793
TI  - Retraction.

PMID- 29592794
TI  - A mortality model based on a mixture distribution function.
AB  - A new mortality model based on a mixture distribution function is proposed. We
      mix a half-normal distribution with a generalization of the skew-normal
      distribution. As a result, we get a six-parameter distribution function that has
      a good fit with a wide variety of mortality patterns. This mixture model is
      fitted to several mortality data schedules and compared with the Siler (five
      parameter) and Heligman-Pollard (eight-parameter) models. Our proposal serves as
      a convenient compromise between the Heligman-Pollard model (which ensures a good
      fit with data but is often overparameterized) and the Siler model (which is more
      compact but fails to capture 'accident humps').

PMID- 29592795
TI  - Phylogenomics of palearctic Formica species suggests a single origin of temporary
      parasitism and gives insights to the evolutionary pathway toward slave-making
      behaviour.
AB  - BACKGROUND: The ants of the Formica genus are classical model species in
      evolutionary biology. In particular, Darwin used Formica as model species to
      better understand the evolution of slave-making, a parasitic behaviour where
      workers of another species are stolen to exploit their workforce. In his book "On
      the Origin of Species" (1859), Darwin first hypothesized that slave-making
      behaviour in Formica evolved in incremental steps from a free-living ancestor.
      METHODS: The absence of a well-resolved phylogenetic tree of the genus prevent an
      assessment of whether relationships among Formica subgenera are compatible with
      this scenario. In this study, we resolve the relationships among the 4 palearctic
      Formica subgenera (Formica str. s., Coptoformica, Raptiformica and Serviformica)
      using a phylogenomic dataset of 945 genes for 16 species. RESULTS: We provide a
      reference tree resolving the relationships among the main Formica subgenera with
      high bootstrap supports. DISCUSSION: The branching order of our tree suggests
      that the free-living lifestyle is ancestral in the Formica genus and that
      parasitic colony founding could have evolved a single time, probably acting as a
      pre-adaptation to slave-making behaviour. CONCLUSION: This phylogenetic tree
      provides a solid backbone for future evolutionary studies in the Formica genus
      and slave-making behaviour.

PMID- 29592796
TI  - C3 glomerulopathy in cystic fibrosis: a case report.
AB  - BACKGROUND: C3 glomerulonephritis is a rare glomerulopathy characterized at renal
      biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an
      electron-dense material in mesangium, subendothelial and subepithelial space. An
      abnormal systemic activation of the alternative pathway of the complement cascade
      is responsible for the development of the disease if triggered by several
      possible environmental conditions. We report the first case in literature of a
      patient affected by cystic fibrosis and C3GN. CASE PRESENTATION: Our case
      involves a young woman with cystic fibrosis, who had persistent microscopic
      hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal
      biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system
      dysregulation was tested and resulted in a strong terminal pathway activation
      proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value <
      400 ng/ml). Next generation sequencing (NGS) showed polymorphism in CFH (p.V62I
      in SCR1) and THBD (p.A473V), already known as pathogenic for C3GN, as well as a
      mutation in C3 (p.R102G) associated only with age-related macular degeneration
      (AMD) so far. Treatment was based on ACE inhibitors and kidney function is
      currently stable (GFR 50 ml/min, serum creatinine 1.7). CONCLUSIONS: The co
      existence of C3 glomerulopathy in a patient with CF, which is characterized by
      chronic infection/inflammation, makes this case an interesting model of chronic
      altered systemic activation of the alternative pathway of the complement cascade.

PMID- 29592797
TI  - Prevalence of and risk factors for tuberculosis among healthcare workers in
      Chinese tuberculosis facilities.
AB  - BACKGROUND: China is one of 22 countries with a high tuberculosis (TB) burden in
      the world. Healthcare workers (HCWs) have a high risk of contracting
      Mycobacterium tuberculosis infection due to insufficient infection control
      practices. We conducted a cross-sectional study to explore the prevalence of TB
      and its associated risk factors among HCWs in Chinese TB facilities. METHODS: Two
      hundred and forty-one TB facilities employing a total of 9663 HCWs were selected
      from 12 provinces in China to represent healthcare settings at the provincial,
      prefectural, and county levels. Structured questionnaires were used to collect
      information on TB infection control practices and HCWs in those facilities. Data
      was double entered into EpiData 3.1; TB prevalence and associated risk factors
      were analyzed using SPSS 21.0 with bivariate and multivariate regression models.
      RESULTS: The results showed that 71 HCWs had been diagnosed with TB, accounting
      for a prevalence of 760/100 000. The multivariate analysis showed that associated
      risk factors included belonging to the age group of 51 years and above (aOR:
      6.17, 95% CI: 1.35-28.28), being a nurse (aOR = 3.09, 95% CI: 1.15-8.32),
      implementation of 0-9 items of management measures (aOR = 2.57, 95% CI: 1.37
      4.80), and implementation of 0-1 items of ventilation measures (aOR = 2.42, 95%
      CI: 1.31-4.47). CONCLUSION: This was the first national large sampling survey on
      TB prevalence among HCWs in China. It was found that the implementation of TB
      infection control practices in some facilities was poor. The TB prevalence in
      HCWs was higher than that in the general population. Therefore, TB infection
      control practices in Chinese medical facilities should be strengthened.

PMID- 29592798
TI  - Comparative investigation on the sizes and scavenger receptor binding of human
      native and modified lipoprotein particles with atomic force microscopy.
AB  - BACKGROUND: The size and receptor-binding abilities of plasma lipoproteins are
      closely related with their structure/functions. Presently, the sizes of native
      lipoproteins have been measured by various methods including atomic force
      microscopy (AFM) whereas the sizes of modified lipoproteins are poorly determined
      and the receptor-binding ability of lipoproteins is less detected and compared at
      the nanoscale. METHODS: Here, AFM was utilized to detect/compare the size and
      scavenger receptor-binding properties of three native human lipoproteins
      including high-density lipoprotein, low-density lipoprotein (LDL), and very low
      density lipoprotein, and two modified human lipoproteins including oxidized and
      acetylated LDL, as well as bovine serum albumin and their antibodies as negative
      and positive controls, respectively. RESULTS: AFM detected that the sizes of
      these lipoproteins are close to the commonly known values and the previously
      reported AFM-detected sizes and that native and modified LDL have different
      height/size. AFM also revealed that the CD36-binding abilities of the five
      lipoproteins are different from one another and from their SR-B1-binding
      abilities and that the anti-CD36/SR-B1 antibodies as positive controls have
      strong CD36/SR-B1-binding abilities. CONCLUSIONS: The data provide important
      information on lipoproteins for better understanding their structures/functions.
      Moreover, the data certify that besides size measurement AFM also can visualize
      receptor-lipoprotein binding at the nanoscale, as well as antigen-antibody
      (scavenger receptors and their antibodies) binding.

PMID- 29592799
TI  - Between-population differences in the genetic and maternal components of body
      mass in roe deer.
AB  - BACKGROUND: Understanding the genetic and environmental mechanisms governing
      variation in morphology or phenology in wild populations is currently an
      important challenge. While there is a general consensus that selection is
      stronger under stressful conditions, it remains unclear whether the evolutionary
      potential of traits should increase or decrease with increasingly stressful
      conditions. Here, we investigate how contrasting environmental conditions during
      growth may affect the maternal and genetic components of body mass in roe deer,
      the most abundant and widespread wild ungulate in Western Europe. Body mass is a
      key life history trait that strongly influences both survival and reproductive
      performance in large herbivores. We used pedigrees and animal models to determine
      the variance components of juvenile and adult winter body mass in two populations
      experiencing contrasting early-life conditions. RESULTS: Our analyses showed that
      roe deer at Chize, where habitat was poor and unpredictable, exhibited very low
      genetic variance in juvenile body mass. Instead, variance in mass was mainly
      driven by among-cohort differences in early-life conditions and maternal
      environment. In contrast, roe deer at Bogesund, where resource availability
      during the critical period of fawn rearing was higher, displayed a substantial
      level of genetic variance in body mass. We discuss the potential role of past
      demography and viability selection on fawn body mass on the erosion of genetic
      variance in the poor habitat. CONCLUSIONS: Our study highlights the importance of
      accounting for both spatial (i.e. between-population variation) and temporal
      (i.e. cohort variation) heterogeneity in environmental conditions, especially in
      early life, to understand the potential for adaptive responses of wild
      populations to selection.

PMID- 29592800
TI  - Evaluation of the effect of methamphetamine on traumatic injury complications and
      outcomes.
AB  - BACKGROUND: This study investigates the impact of methamphetamine use on trauma
      patient outcomes. METHODS: This retrospective study analyzed patients between 18
      and 55 years old presenting to a single trauma center in San Bernardino County,
      CA who sustained traumatic injury during the 10-year study period (January 1st,
      2005 to December 31st, 2015). Routine serum ethanol levels and urine drug screens
      (UDS) were completed on all trauma patients. Exclusion criteria included patients
      with an elevated serum ethanol level (> 0 mg/dL). Those who screened positive on
      UDS for only methamphetamine and negative for cocaine and cannabis (MA(+)) were
      compared to those with a triple negative UDS for methamphetamine, cocaine, and
      cannabis (MA(-)). The primary outcome studied was the impact of a methamphetamine
      positive drug screen on hospital mortality. Secondary outcomes included length of
      stay (LOS), heart rate, systolic and diastolic blood pressure (SBP and DBP,
      respectively), and total amount of blood products utilized during
      hospitalization. To analyze the effect of methamphetamine, age, gender, injury
      severity score, and mechanism of injury (blunt vs. penetrating) were matched
      between MA(-) and MA(+) through a propensity matching algorithm. RESULTS: After
      exclusion, 2538 patients were included in the final analysis; 449 were patients
      in the MA(+) group and 2089 patients in the MA(-) group. A selection of 449 MA(-)
      patients were matched with the MA(+) group based on age, gender, injury severity
      score, and mechanism of injury. This led to a final sample size of 898 patients
      with 449 patients in each group. No statistically significant change was observed
      in hospital mortality. Notably, a methamphetamine positive drug screen was
      associated with a longer LOS (median of 4 vs. 3 days in MA(+) and MA(-),
      respectively, p < 0.0001), an increased heart rate at the scene (103 vs. 94 bpm
      for MA(+) and MA(-), respectively, p = 0.0016), and an increased heart rate upon
      arrival to the trauma center (100 vs. 94 bpm for MA(+) and MA(-), respectively, p
      < 0.0001). Moreover, the MA(+) group had decreased SBP at the scene compared to
      the MA(-) group (127 vs. 132 bpm for MA(+) and MA(-), respectively, p = 0.0149),
      but SBP was no longer statistically different when patients arrived at the trauma
      center (p = 0.3823). There was no significant difference in DBP or in blood
      products used. CONCLUSION: Methamphetamine positive drug screens in trauma
      patients were not associated with an increase in hospital mortality; however, a
      methamphetamine positive drug screen was associated with a longer LOS and an
      increased heart rate.

PMID- 29592801
TI  - Standardised alcohol screening in primary health care services targeting
      Aboriginal and Torres Strait Islander peoples in Australia.
AB  - INTRODUCTION AND AIMS: Aboriginal and Torres Strait Islander Community Controlled
      Health Services (ACCHSs) around Australia have been asked to standardise
      screening for unhealthy drinking. Accordingly, screening with the 3-item AUDIT-C
      (Alcohol Use Disorders Identification Test-Consumption) tool has become a
      national key performance indicator. Here we provide an overview of suitability of
      AUDIT-C and other brief alcohol screening tools for use in ACCHSs. METHODS: All
      peer-reviewed literature providing original data on validity, acceptability or
      feasibility of alcohol screening tools among Indigenous Australians was reviewed.
      Narrative synthesis was used to identify themes and integrate results. RESULTS:
      Three screening tools-full AUDIT, AUDIT-3 (third question of AUDIT) and CAGE (Cut
      down, Annoyed, Guilty and Eye-opener) have been validated against other
      consumption measures, and found to correspond well. Short forms of AUDIT have
      also been found to compare well with full AUDIT, and were preferred by primary
      care staff. Help was often required with converting consumption into standard
      drinks. Researchers commented that AUDIT and its short forms prompted reflection
      on drinking. Another tool, the Indigenous Risk Impact Screen (IRIS), jointly
      screens for alcohol, drug and mental health risk, but is relatively long (13
      items). IRIS has been validated against dependence scales. AUDIT, IRIS and CAGE
      have a greater focus on dependence than on hazardous or harmful consumption.
      DISCUSSION AND CONCLUSIONS: Detection of unhealthy drinking before harms occur is
      a goal of screening, so AUDIT-C offers advantages over tools like IRIS or CAGE
      which focus on dependence. AUDIT-C's brevity suits integration with general
      health screening. Further research is needed on facilitating implementation of
      systematic alcohol screening into Indigenous primary healthcare.

PMID- 29592802
TI  - Physiotherapists' views of implementing a stratified treatment approach for
      patients with low back pain in Germany: a qualitative study.
AB  - BACKGROUND: The STarT-Back-Approach (STarT: Subgroups for Targeted Treatment) was
      developed in the UK and has demonstrated clinical and cost effectiveness. Based
      on the results of a brief questionnaire, patients with low back pain are
      stratified into three treatment groups. Since the organisation of physiotherapy
      differs between Germany and the UK, the aim of this study is to explore German
      physiotherapists' views and perceptions about implementing the STarT-Back
      Approach. METHODS: Three two-hour think-tank workshops with physiotherapists were
      conducted. Focus groups, using a semi-structured interview guideline, followed a
      presentation of the STarT-Back-Approach, with discussions audio recorded,
      transcribed and qualitatively analysed using content analysis. RESULTS: Nineteen
      physiotherapists participated (15 female, mean age 41.2 (SD 8.6) years). Three
      main themes emerged, each with multiple subthemes: 1) the intervention (15
      subthemes), 2) the healthcare context (26 subthemes) and 3) individual
      characteristics (8 subthemes). Therapists' perceptions of the extent to which the
      STarT-Back intervention would require changes to their normal clinical practice
      varied considerably. They felt that within their current healthcare context,
      there were significant financial disincentives that would discourage German
      physiotherapists from providing the STarT-Back treatment pathways, such as the
      early discharge of low-risk patients with supported self-management materials.
      They also discussed the need for appropriate standardised graduate and post
      graduate skills training for German physiotherapists to treat high-risk patients
      with a combined physical and psychological approach (e.g., communication skills).
      CONCLUSIONS: Whilst many German physiotherapists are positive about the STarT
      Back-Approach, there are a number of substantial barriers to implementing the
      matched treatment pathways in Germany. These include financial disincentives
      within the healthcare system to early discharge of low-risk patients. Therapists
      also highlighted the need for solutions in respect of scalable physiotherapy
      training to gain skills in combined physical and psychological approaches.

PMID- 29592803
TI  - Development an effective system to expression recombinant protein in E. coli via
      comparison and optimization of signal peptides: Expression of Pseudomonas
      fluorescens BJ-10 thermostable lipase as case study.
AB  - BACKGROUND: Thermostable lipases from microbial sources have been substantially
      overexpressed in E. coli, however, these enzymes are often produced with low
      level enzymatic activity and mainly in the form of inclusion bodies. Several
      studies have reported that the secretory production of recombinant proteins fused
      their N-terminus to a signal peptide has been employed to resolve the problem. In
      general, the feasibility of this approach largely depends on the secretory
      pathway of signal peptide and the type of target protein to be secreted. This
      study was performed to compare and optimize signal peptides for efficient
      secretion of thermostable lipase lipBJ10 from Pseudomonas fluorescens BJ-10.
      Meanwhile, a comparative study between this method and cytoplasmic secretion was
      implemented in secreting soluble and active lipases. RESULTS: Fusion expression
      using six signal peptides, i.e., PelB and five native E. coli signal peptides, as
      fusion partners produced more soluble and functional recombinant lipBJ10 than non
      fusion expression. Recombinant lipBJ10, fused to these six diverse signal
      peptides, was secreted into the periplasm in E. coli. The total lipase activity
      in all cases of fusion expression was higher than those in non-fusion expression.
      The relative activity peaked when lipBJ10 was fused to DsbA, yielding a value
      73.3 times greater than that of the non-fusion protein. When DsbA was used as the
      fusion partner, the highest activity (265.41 U/ml) was achieved with the least
      formation of inclusion bodies; the other four E. coli signal peptides, to some
      extent, led to low activity and insoluble inclusion bodies. Therefore, DsbA is
      the optimal signal peptide partner to fuse with lipBJ10 to efficiently produce
      soluble and functional protein. CONCLUSION: We found that fusing to these signal
      peptides, especially that of DsbA, can significantly decrease the formation of
      inclusion bodies and enhance the function and solubility of lipBJ10 compared to
      non-fusion lipBJ10. Our results reported here can provide a reference for the
      high-level expression of other lipases with respect to a possible industrial
      application.

PMID- 29592804
TI  - Metabolic engineering of a xylose pathway for biotechnological production of
      glycolate in Escherichia coli.
AB  - BACKGROUND: Glycolate is a valuable chemical with extensive applications in many
      different fields. The traditional methods to synthesize glycolate are quite
      expensive and toxic. So, the biotechnological production of glycolate from
      sustainable feedstocks is of interest for its potential economic and
      environmental advantages. D-Xylose is the second most abundant sugar in nature
      and accounts for 18-30% of sugar in lignocellulose. New routes for the conversion
      of xylose to glycolate were explored. RESULTS: Overexpression of aceA and ghrA
      and deletion of aceB in Escherichia coli were examined for glycolate production
      from xylose, but the conversion was initially ineffective. Then, a new route for
      glycolate production was established in E. coli by introducing NAD+-dependent
      xylose dehydrogenase (xdh) and xylonolactonase (xylC) from Caulobacter
      crescentus. The constructed engineered strain Q2562 produced 28.82 +/- 0.56 g/L
      glycolate from xylose with 0.60 +/- 0.01 g/L/h productivity and 0.38 +/- 0.07 g/g
      xylose yield. However, 27.18 +/- 2.13 g/L acetate was accumulated after
      fermentation. Deletions of iclR and ackA were used to overcome the acetate
      excretion. An ackA knockout resulted in about 66% decrease in acetate formation.
      The final engineered strain Q2742 produced 43.60 +/- 1.22 g/L glycolate, with
      0.91 +/- 0.02 g/L/h productivity and 0.46 +/- 0.03 g/g xylose yield. CONCLUSIONS:
      A new route for glycolate production from xylose was established, and an
      engineered strain Q2742 was constructed from this new explored pathway. The
      engineering strain showed the highest reported productivity of glycolate to date.
      This research opened up a new prospect for bio-refinery of xylose and an
      alternative choice for industrial production of glycolate.

PMID- 29592805
TI  - Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.
AB  - BACKGROUND: Drug-induced liver injury (DILI) is a common complication of
      tuberculosis treatment. We utilised data from the REMoxTB clinical trial to
      describe the incidence of predisposing factors and the natural history in
      patients with liver enzyme levels elevated in response to tuberculosis treatment.
      METHODS: Patients received either standard tuberculosis treatment (2EHRZ/4HR), or
      a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid
      arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were
      measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during
      reported adverse events. Patients included were those receiving at least one dose
      of drug and with two or more hepatic enzyme measurements. RESULTS: A total of
      1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR).
      DILI was defined as peak alanine aminotransferase (ALT) >= 5 times the upper
      limit of normal (5 * ULN) or ALT >= 3 * ULN with total bilirubin > 2 * ULN. DILI
      was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days
      (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard
      tuberculosis therapy, 41 experienced clinically significant enzyme elevations
      (peak ALT >= 3 * ULN). On standard therapy, 21.1% of patients aged >55 years
      developed a peak ALT/aspartate aminotransferase (AST) >= 3 * ULN (p = 0.01) and
      15% of HIV-positive patients experienced a peak ALT/AST >= 3 * ULN compared to 9%
      of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in
      isoniazid-containing regimens vs no-isoniazid regimens (p < 0.05), and lower in
      moxifloxacin-containing arms vs no-moxifloxacin arms (p < 0.05). Patients
      receiving isoniazid reached a peak ALT >= 3 * ULN 9.5 days earlier than those on
      the ethambutol arm (median time of 28 days vs 18.5 days). Of the 67 Asian
      patients with a peak ALT/AST >= 3 * ULN, 57 (85.1%) were on an isoniazid
      containing regimen (p = 0.008). CONCLUSIONS: Our results provide evidence of the
      risk of DILI in tuberculosis patients on standard treatment. Older patients on
      standard therapy, HIV-positive patients, Asian patients and those receiving
      isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic
      enzymes during the first 2 months of standard therapy detected approximately 75%
      of patients with a peak enzyme elevation >=3 * ULN, suggesting this should be a
      standard of care. These results provide evidence for the potential of
      moxifloxacin in hepatic sparing.

PMID- 29592806
TI  - beta-aminoisobutyric acid attenuates LPS-induced inflammation and insulin
      resistance in adipocytes through AMPK-mediated pathway.
AB  - BACKGROUND: beta-aminoisobutyric acid (BAIBA) is produced in skeletal muscle
      during exercise and has beneficial effects on obesity-related metabolic disorders
      such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to
      prevent high fat diet (HFD)-induced inflammation and insulin resistance in
      adipose tissue though anti-inflammatory effects in obesity. Previous reports have
      also demonstrated strong anti-inflammatory effects of BAIBA. METHODS: We used
      BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the
      effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes.
      Insulin signaling-mediated proteins and inflammation markers were measured by
      Western blot analysis. Secretion of pro-inflammatory cytokines were measured by
      ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red
      O. Statistical analysis was performed by ANOVA and student's t test. RESULTS:
      BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as
      lipid accumulation after full differentiation. We showed that BAIBA treatment
      stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose
      dependent manner and lipopolysaccharide (LPS)-induced secretion of pro
      inflammatory cytokines such as TNFalpha and MCP-1 was abrogated in BAIBA-treated
      3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFkappaB
      and IkappaB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced
      impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and
      fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA
      significantly restored these changes. CONCLUSIONS: We demonstrated anti
      inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3
      L1 cells treated with LPS through AMPK-dependent signaling. These results provide
      evidence for the beneficial effects of BAIBA not only in liver and skeletal
      muscle cells but also in adipose tissue.

PMID- 29592807
TI  - Bursectomy for advanced gastric cancer: an update meta-analysis.
AB  - BACKGROUND: The present meta-analysis was to explore the surgical and oncological
      outcomes of bursectomy for advanced gastric cancer (AGC). METHODS: Relevant
      studies that evaluated the role of bursectomy for AGC were comprehensively
      examined to perform a meta-analysis. The primary outcomes were overall survival
      (OS) and disease-free survival (DFS). The secondary outcomes were the number of
      harvested lymph nodes (LNs), operation time, operative bleeding, hospital stay,
      postoperative complication and mortality. RESULTS: A total of seven studies
      comprising 2633 cases (1176 cases in the bursectomy group and 1457 cases in the
      non-bursectomy group) were finally included. There was no significant difference
      in OS (HR 0.95, P = 0.647) and DFS (HR 0.99, P = 0.936) between the two groups.
      Even for patients with serosa-penetrating tumours, OS was comparable between the
      two groups (HR 0.87, P = 0.356). The operation time of the bursectomy group was
      longer (weighted mean difference, WMD 32.76 min, P = 0.002). No significant
      difference was found between the two groups in terms of the number of dissected
      LNs (WMD 5.86, P = 0.157), operative bleeding (WMD 66.99 ml, P = 0.192) and
      hospital stay (WMD - 0.15 days, P = 0.766). The overall postoperative
      complication (relative risk, RR 1.08, P = 0.421) and mortality (RR 0.44, P =
      0.195) were similar between two groups. CONCLUSIONS: This meta-analysis indicated
      that bursectomy is time-consuming without increasing the number of harvested LNs.
      Although bursectomy can be safely performed without increasing complications and
      mortality, it does not prolong the OS and DFS of AGC patients, including patients
      with serosa-penetrating tumours. Therefore, bursectomy should not be recommended
      as a standard procedure for AGC.

PMID- 29592808
TI  - Correction to: A sophisticated, differentiated Golgi in the ancestor of
      eukaryotes.
AB  - Upon publication of the original article, Barlow et al. [1], the authors noticed
      that Fig. 4b contained an inaccuracy when additional data is taken into account.
      We inferred a loss of GRASP in the common ancestor of cryptophytes and
      archaeplastids, based on the absence of identified homologues in the data from
      taxa that we analyzed, which include Cyanidioschyzon merolae as the single
      representative of red algae.

PMID- 29592809
TI  - Exploring the potential of black tea based flavonoids against hyperlipidemia
      related disorders.
AB  - BACKGROUND: In recent decade, Hyperlipidemia related disorders like obesity,
      hypercholesterolemia and diabetes are considered as the leading killers for
      mankind. Fundamental nexus between nutrition and health diverting the consumers
      focus towards plant based natural products as a remedy against various metabolic
      syndrome. Considering this, present study was conducted to explicate the role of
      black tea polyphenols such as Theaflavins and thearubigins therapeutic potential
      to tackle targeted maladies especially oxidative stress related disorders like
      hypercholesterolemia and diabetes. METHODS: The mandate of current investigation
      was to explore the hypoglycemic and hypocholestrolemic perspective of isolated
      theaflavin and thearubigins through a model feeding trial. For the purpose,
      theaflavin & thearubigins were isolated from black tea through solvent partition
      method and utilize to form three types of nutraceutical drinks (theaflavin,
      thearubigins & theaflavin + thearubigins based) alongside control to be further
      utilized in bioefficacy trial. In bioefficacy trial, three types of independent
      studies were design on the bases of diet by involving 20 male wistar rats in each
      study (5 for each group). In study I, normal diet was administrated while, in
      study II & III high cholesterol and high sucrose diet was given, respectively
      along with prepared nutraceutical drinks to synchronize their therapeutic effect
      for a period of 56 days. At the termination of trial, Feed & drink intakes, body
      weight, total cholesterol, LDL, HDL, triglycerides, glucose and insulin levels
      were measured. RESULTS: The results indicated reduction in cholesterol, LDL and
      triglycerides levels of experimental rats in all studies with significant
      increase in HDL. In this context, theaflavin based drink imparted maximum
      reduction in cholesterol (3.75, 11.03 & 10.39%), LDL (3.84, 14.25& 10.84%) &
      triglycerides (2.99, 8.54 & 6.65%) in respective studies compared to thearubigins
      and theaflavin + thearubigins based drinks. However, theaflavin+ thearubigins
      based drink caused highest glucose decline and maximum insulin increase in all
      studies as compared to other nutraceutical drinks. The reported value for the
      insulin increase were 13.02 +/- 1.02 & 14.55 +/- 1.13, 10.09 +/- 0.15 & 11.59 +/-
      0.86 for Hyperglycemic and Hypocholestrolemic rats respectively compared to
      control (7.84 +/- 0.45 & 9.10 +/- 0.41) for study I and II. CONCLUSIONS: In the
      nutshell, theaflavin and thearubigins based dietary interventions are helpful to
      alleviate the hypercholestrolemia and hyperglycemia and should be promoted as
      parallel therapy to combat these disorders.

PMID- 29592810
TI  - CRISPR/Cas9: the Jedi against the dark empire of diseases.
AB  - Advances in Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR
      associated system (CRISPR/Cas9) has dramatically reshaped our ability to edit
      genomes. The scientific community is using CRISPR/Cas9 for various
      biotechnological and medical purposes. One of its most important uses is
      developing potential therapeutic strategies against diseases. CRISPR/Cas9 based
      approaches have been increasingly applied to the treatment of human diseases like
      cancer, genetic, immunological and neurological disorders and viral diseases.
      These strategies using CRISPR/Cas9 are not only therapy oriented but can also be
      used for disease modeling as well, which in turn can lead to the improved
      understanding of mechanisms of various infectious and genetic diseases. In
      addition, CRISPR/Cas9 system can also be used as programmable antibiotics to kill
      the bacteria sequence specifically and therefore can bypass multidrug resistance.
      Furthermore, CRISPR/Cas9 based gene drive may also hold the potential to limit
      the spread of vector borne diseases. This bacterial and archaeal adaptive immune
      system might be a therapeutic answer to previous incurable diseases, of course
      rigorous testing is required to corroborate these claims. In this review, we
      provide an insight about the recent developments using CRISPR/Cas9 against
      various diseases with respect to disease modeling and treatment, and what future
      perspectives should be noted while using this technology.

PMID- 29592811
TI  - Novel microtubule inhibitor MPT0B098 inhibits hypoxia-induced epithelial-to
      mesenchymal transition in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Tumor hypoxia-induced epithelial-mesenchymal transition (EMT) is
      critical in promoting cancer metastasis. We recently discovered a novel
      microtubule inhibitor, MPT0B098, that employs a novel antitumor mechanism. It
      destabilizes hypoxia-inducible factor (HIF)-1alpha mRNA by blocking the function
      of human antigen R. Thus, we proposed that MPT0B098 modulates hypoxia-induced
      EMT. METHODS: In vitro IC50 values were determined through the methylene blue dye
      assay. To investigate molecular events, reverse transcriptase-polymerase chain
      reaction, Western blotting, immunofluorescence staining, and wound healing assay
      were employed. RESULTS: MPT0B098 significantly inhibited HIF-1alpha expression,
      epithelial-to-mesenchymal morphology changes, and migratory ability in the human
      head and neck squamous cell carcinoma cell line OEC-M1. Furthermore, after
      MPT0B098 treatment, the expression of two mesenchymal markers, vimentin and N
      cadherin, was downregulated under hypoxic conditions. Moreover, MPT0B098
      suppressed hypoxia-induced EMT in part by inhibiting EMT-activating transcription
      factors, Twist and SNAI2/Slug. In addition, the inhibition of hypoxia-induced F
      actin rearrangement and focal adhesion kinase phosphorylation may have
      contributed to suppression of EMT by MPT0B098in OEC-M1 cells. MPT0B098
      significantly inhibited transforming growth factor(TGF)-beta-induced
      phosphorylation of receptor-associated Smad2/3 by downregulating TGF-beta mRNA
      and protein expression. CONCLUSIONS: Taken together, this study provides a novel
      insight into the role of MPT0B098 in inhibiting hypoxia-induced EMT, suggesting
      its potential use for treating head and neck cancers.

PMID- 29592812
TI  - Discovery of physiological and cancer-related regulators of 3' UTR processing
      with KAPAC.
AB  - 3' Untranslated regions (3' UTRs) length is regulated in relation to cellular
      state. To uncover key regulators of poly(A) site use in specific conditions, we
      have developed PAQR, a method for quantifying poly(A) site use from RNA
      sequencing data and KAPAC, an approach that infers activities of oligomeric
      sequence motifs on poly(A) site choice. Application of PAQR and KAPAC to RNA
      sequencing data from normal and tumor tissue samples uncovers motifs that can
      explain changes in cleavage and polyadenylation in specific cancers. In
      particular, our analysis points to polypyrimidine tract binding protein 1 as a
      regulator of poly(A) site choice in glioblastoma.

PMID- 29592813
TI  - Cancer Genome Interpreter annotates the biological and clinical relevance of
      tumor alterations.
AB  - While tumor genome sequencing has become widely available in clinical and
      research settings, the interpretation of tumor somatic variants remains an
      important bottleneck. Here we present the Cancer Genome Interpreter, a versatile
      platform that automates the interpretation of newly sequenced cancer genomes,
      annotating the potential of alterations detected in tumors to act as drivers and
      their possible effect on treatment response. The results are organized in
      different levels of evidence according to current knowledge, which we envision
      can support a broad range of oncology use cases. The resource is publicly
      available at http://www.cancergenomeinterpreter.org .

PMID- 29592814
TI  - QAPA: a new method for the systematic analysis of alternative polyadenylation
      from RNA-seq data.
AB  - Alternative polyadenylation (APA) affects most mammalian genes. The genome-wide
      investigation of APA has been hampered by an inability to reliably profile it
      using conventional RNA-seq. We describe 'Quantification of APA' (QAPA), a method
      that infers APA from conventional RNA-seq data. QAPA is faster and more sensitive
      than other methods. Application of QAPA reveals discrete, temporally coordinated
      APA programs during neurogenesis and that there is little overlap between genes
      regulated by alternative splicing and those by APA. Modeling of these data
      uncovers an APA sequence code. QAPA thus enables the discovery and
      characterization of programs of regulated APA using conventional RNA-seq.

PMID- 29592815
TI  - Treatment optimization of angiotensin converting enzyme inhibitors and associated
      factors in Ayder Comprehensive Specialized Hospital: a cross-sectional study.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors have morbidity and mortality
      benefits in heart failure. Failure to optimize treatment using these medications
      increases hospitalizations, worsens signs and symptoms of heart failure, and
      reduces the overall treatment outcome. Therefore, the main purpose of this study
      was to assess the practice of treatment optimization of these medications and
      associated factors. RESULTS: A hospital-based cross-sectional study was conducted
      on 61 ambulatory heart failure patients, recruited using a convenience sampling
      technique, from February 25 to May 24, 2016 at the cardiology clinic of Ayder
      Comprehensive Specialized Hospital. Descriptive, inferential and Kaplan-Meier
      'tolerability' analyses were employed. All patients were taking only enalapril as
      part of their angiotensin converting enzyme inhibitor treatment. According to the
      2013 American College of Cardiology/American Heart Association guideline, about
      fourth-fifth (80.3%) of the patients were tolerating to the hypotensive effect of
      enalapril. The dose of enalapril was timely titrated (every 2-4 weeks) and was
      optimized for only 11.5 and 27.8% of the patients, respectively. Considering the
      tolerance, timely titration, and dose optimization, only 3.3% of the overall
      enalapril treatment was optimized. Multivariate regression results showed that
      the odds of having timely titration of enalapril for patients who were taking
      enalapril and calcium channel blockers were almost 20 times [adjusted odds ratio
      (AOR) = 21.68, 95% confidence interval (CI) 1.23-383.16, p < 0.036] more compared
      to patients who were taking enalapril and beta-blockers. A Log Rank Chi Square
      result showed a 19.42 magnitude of better toleration of enalapril (p < 0.001) for
      patients who were taking enalapril for more than 1 year compared to less than a
      year. CONCLUSION: This study provides a platform for assessment of the treatment
      optimization practice of enalapril, which remains the pressing priority and found
      to be poor in the ambulatory setting, despite a better tolerability to the
      hypotensive effect of enalapril. We call for greater momentum of efforts by
      health care providers in optimizing the treatment practice to benchmark with
      other optimization practices.

PMID- 29592816
TI  - The Abeta protofibril selective antibody mAb158 prevents accumulation of Abeta in
      astrocytes and rescues neurons from Abeta-induced cell death.
AB  - BACKGROUND: Currently, several amyloid beta (Abeta) antibodies, including the
      protofibril selective antibody BAN2401, are in clinical trials. The murine
      version of BAN2401, mAb158, has previously been shown to lower the levels of
      pathogenic Abeta and prevent Abeta deposition in animal models of Alzheimer's
      disease (AD). However, the cellular mechanisms of the antibody's action remain
      unknown. We have recently shown that astrocytes effectively engulf Abeta42
      protofibrils, but store rather than degrade the ingested Abeta aggregates. In a
      co-culture set-up, the incomplete degradation of Abeta42 protofibrils by
      astrocytes results in increased neuronal cell death, due to the release of
      extracellular vesicles, containing N-truncated, neurotoxic Abeta. METHODS: The
      aim of the present study was to investigate if the accumulation of Abeta in
      astrocytes can be affected by the Abeta protofibril selective antibody mAb158. Co
      cultures of astrocytes, neurons, and oligodendrocytes, derived from embryonic
      mouse cortex, were exposed to Abeta42 protofibrils in the presence or absence of
      mAb158. RESULTS: Our results demonstrate that the presence of mAb158 almost
      abolished Abeta accumulation in astrocytes. Consequently, mAb158 treatment
      rescued neurons from Abeta-induced cell death. CONCLUSION: Based on these
      findings, we conclude that astrocytes may play a central mechanistic role in anti
      Abeta immunotherapy.

PMID- 29592817
TI  - Dysregulation of chemokine receptor expression and function in leukocytes from
      ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is rapidly progressive adult-onset motor
      neuron disease characterized by the neurodegeneration of both upper and lower
      motor neurons in the cortex and the spinal cord; the majority of patients succumb
      to respiratory failure. Although the etiology is not yet fully understood, there
      is compelling evidence that ALS is a multi-systemic disorder, with peripheral
      inflammation critically contributing to the disease process. However, the full
      extent and nature of this immunological dysregulation remains to be established,
      particularly within circulating blood cells. Therefore, the aim of the present
      study was to identify dysregulated inflammatory molecules in peripheral blood
      cells of ALS patients and analyze for functional consequences of the observed
      findings. To this end, we employed flow cytometry-based screening to quantify the
      surface expression of major chemokine receptors and integrins. A significantly
      increased expression of CXCR3, CXCR4, CCL2, and CCL5 was observed on T cells in
      ALS patients compared to healthy controls. Intriguingly, the expression was even
      more pronounced in patients with a slow progressive phenotype. To further
      investigate the functional consequences of this altered surface expression, we
      used a modified Boyden chamber assay to measure chemotaxis in ALS patient-derived
      lymphocytes. Interestingly, chemoattraction with the CXCR3-Ligand IP10 led to
      upregulated migratory behavior of ALS lymphocytes compared to healthy controls.
      Taken together, our data provides evidence for a functional dysregulation of IP10
      directed chemotaxis in peripheral blood cells in ALS patients. However, whether
      the chemokine itself or its receptor CXCR3, or both, could serve as potential
      therapeutic targets in ALS requires further investigations.

PMID- 29592819
TI  - Editorial.

PMID- 29592820
TI  - Outsourcing critical financial system operations.
AB  - Payments Canada provides Canada's national payments systems and is responsible
      for the clearing and settlement infrastructure, processes and rules that underpin
      the exchange of billions of dollars each day through the Canadian economy.
      Strategic sourcing is a reality for this small organisation with a broad scope of
      national regulations and global standards to comply with. This paper outlines
      Payments Canada's approach to outsourcing its critical financial system
      operations, which centres on four key principles: strong relationship management;
      continuous learning, recording and reporting; evaluating the business landscape;
      and a commitment to evolving the organisation to greater resilience. This last
      point is covered in detail with an exploration of the organisation's resilience
      and security strategy as well as its risk appetite. As Payments Canada progresses
      to its future state, which includes modernising its core payment systems,
      underlying rules and standards, risk management for the industry as a whole will
      remain at the forefront of its collective mind. The expectation is that
      outsourcing will remain a fundamental element of its operating model in future, a
      strategy that will ensure the organisation can focus on its core business
      competencies and eliminate the need to develop and support in-house expertise in
      commodity areas.

PMID- 29592818
TI  - Social-support needs among adolescents living with HIV in transition from
      pediatric to adult care in Cambodia: findings from a cross-sectional study.
AB  - BACKGROUND: Understanding the circumstances of adolescents living with HIV is
      critical in designing adolescent-friendly services that will facilitate
      successful transition from pediatric to adult care. This study describes access,
      utilization and ongoing social support needs among adolescents living with HIV
      aged 15-17 in transition from pediatric to adult HIV care in Cambodia. METHODS: A
      cross-sectional study was conducted among 328 adolescents, randomly selected from
      11 antiretroviral therapy (ART) clinics across the country. Descriptive analyses
      were conducted to summarize their characteristics, access to social support and
      ongoing support needs among male and female adolescents. RESULTS: Mean age of the
      study participants was 15.8 (SD = 0.8) years. Just over half (55.2%) were male.
      Most had at least one deceased parent (mother 50.9%; father 60.5%), and majority
      were living with biological parents (40.8%) or relatives (49.3%). A third came
      from families with an ID poor card, and 21.0% were working for pay. Almost half
      (46.6%) reported that their family had received social support for their health
      care, including food support (76.5%), school allowance (62.1%), transport
      allowance to ART clinics (53.6%), psychosocial counseling (35.3%), vocational
      training (22.9%) or home visits (11.1%). Several ongoing social support needs
      were identified, including ongoing inability to cover health expenses unless they
      are supported by health insurance or health equity fund (55.0%). In addition,
      adolescents reported having been asked to come back earlier than their scheduled
      appointment (13.7%), having had to purchase their own drugs (2.7%), experiencing
      HIV stigma (32.0%), having been denied housing or food due to HIV (8.2%) or
      failing to attend school within the past month partly because of HIV (16.8%). Two
      thirds did not have access to peer support groups. CONCLUSIONS: Social protection
      mechanisms are reaching some adolescents in need, while other remain without
      social support due to discontinuities in health and social care. Multi-sectoral
      interventions, supporting school attendance, adolescent-friendly clinic
      scheduling, reductions in child employment, mitigation of HIV-related stigma and
      strengthening of peer-to-peer support are required to improve coverage of social
      protection interventions for adolescents in transition.

PMID- 29592821
TI  - Preparing for campus demonstrations and protests: Four key focus areas.
AB  - Over the past few years, the number of demonstrations and protests in Western
      countries has been increasing. These protests have tested the limits of free
      speech and expression, leading to individuals and groups attempting to, and in
      some cases succeeding in, shutting down speech with which they do not agree or
      find offensive. This has been particularly acute on college campuses, most
      notably at the University of California, Berkeley and Auburn University in
      Alabama, where speakers with far-right conservative views were forced to cancel
      their planned speeches because of safety and security concerns. As a result,
      colleges and universities throughout the USA are re-examining their policies and
      procedures for speaking engagements and demonstrations and protests, and how to
      manage them effectively while keeping their campus communities safe. This paper
      suggests methods by which universities can put into place policies, procedures
      and guidelines to minimise the possibility of an event becoming violent and
      overwhelming university resources while at the same time balancing the need for
      security and an environment that promotes the free exchange of ideas and
      expression.

PMID- 29592822
TI  - The true value and return on investment of business continuity.
AB  - The phrase return on investment (ROI) is commonly heard when groups or
      organisations attempt to demonstrate the value of a particular activity. 'Is it
      good for us?', 'Is it worth the investment?' and 'Should we continue to fund the
      endeavour?' are all valid and important questions. The challenge for business
      continuity professionals is to address the question, 'What is the ROI of business
      continuity?' in ways that will be meaningful to the person wielding the budget
      stick. In the 'olden days', colleagues would point to their business impact
      analysis, with pie charts and bar graphs showing the cost of business downtime if
      an event occurred. They would sit back and say, 'See? We provide ROI because we
      addressed The Bad Thing!'. But is that really the best that continuity
      professionals can do? This paper peels back the question of ROI and addresses the
      value proposition of business continuity. The goal is to broaden the
      conversation, by instead of talking about how much money business continuity
      efforts will save the company, and instead to focus on the value that business
      continuity provides every day.

PMID- 29592823
TI  - Business continuity and risk management at a strategic level: Case study of the
      Flemish government.
AB  - The Flemish government comprises a number of different departments and agencies
      with the autonomy to optimise their service level in a proactive and resilient
      manner. Recently, the Flemish government defined four organisational values:
      openness, decisiveness, trust and agility. In addition, the Internal Audit Agency
      developed guidelines concerning internal control and organisational management,
      in which risk management was emphasised. In combination with goal setting and
      process management, this paper considers risk management as a starting point for
      the overall management of Flemish government entities. The paper then develops
      tools to support the establishment of business continuity and risk management
      processes. These tools fit into the organisation's strategic framework and are
      easy to understand, pragmatically designed and flexible in their use. The paper
      goes on to illustrate how the Department of the Chancellery and Public Governance
      is implementing BCM and risk management, and how it is integrating BCM, risk
      management and crisis management. It will then focus on the Flemish government's
      long-term strategy across the boundaries between the different entities and the
      question of how risk management can become a useful tool for policy makers.

PMID- 29592824
TI  - A customer-insight led approach to building operational resilience.
AB  - High-profile failures over the past few years have led to the disruption of
      banking services in the UK, with some banks' customers left unable to make or
      receive payments, check balances or access cash for days or weeks. Technological
      advances and a push towards remote channels have increased customer expectations
      of 'always on' - any time, any place, anywhere - and with disruptions lasting
      anything from a few minutes to nearly a month, the regulator is also taking an
      interest. Nationwide Building Society has responded positively to this challenge
      by defining its operational resilience strategy, a long-term plan aimed at
      minimising the likelihood and impact of future disruptions. Customer research was
      used in order to understand customer expectations, as well as define and
      prioritise its end-to-end customer journeys, known as business service lines. A
      comprehensive mapping exercise facilitated the development of strategies and
      investment projects to address identified vulnerabilities and increase
      resilience.

PMID- 29592825
TI  - Business continuity and disaster management within the public service in relation
      to a national development plan.
AB  - Within South Africa, few public service departments understand the concepts of
      business continuity management (BCM) and what it takes to implement a well
      constructed business continuity plan. Likewise, few of these entities understand
      the purpose of designing and maintaining resilient systems that are immune to
      incidents. This paper discusses the integration of the South African Disaster
      Management Act 2002, the Disaster Management Framework and the National
      Development Plan, linking these to BCM, through a resilience period model, as a
      means for the implementation of resilience strategies. The goals of the National
      Development Plan are outlined with a view to how resilience can be achieved in
      each. A resilience period model has been advocated for the implementation of
      projects within the public sector in order to provide continuity and
      sustainability.

PMID- 29592826
TI  - Implementing a community recovery programme.
AB  - How should recovery be understood in the aftermath of a major incident? Bringing
      together the appropriate resources can be a challenge in its own right. How
      should one understand the complex needs of the affected community? What do those
      working in recovery need to implement to ensure a fully integrated recovery
      operation? When trying to formulate a recovery plan, what lessons have been
      learned from previous incidents? This paper suggests some points for
      consideration and implementation.

PMID- 29592827
TI  - Managing stress in a crisis.
AB  - Crisis situations are inherently uncertain and threatening. Although the primal
      stress reactions they provoke deliver some advantages, they so severely restrict
      intellect and behaviour that consultants observe crisis teams making the same
      mistakes over and again. Stress risks can be managed before, during and after a
      crisis. Crisis planning can select the right people, control the crisis team
      environment, and mitigate fatigue risks and memory demands. Because stress
      reactions are primitive, stress can be manipulated at a remarkably primitive
      level and teams can increase their resilience through such basics as sleep and
      breathing skills. Teams can learn to manipulate perceptions of danger, to
      tolerate uncertainty and to become comfortable making decisions which were
      reasonable at the time. Crisis leaders can frame the crisis as a challenge and
      options as gains, and can ensure the team avoids groupthink and challenges the
      paradigm. Where individuals are trained to apply critical thinking processes,
      intuitive decision-making is not only fast, but also accurate, and helps to
      challenge assumptions, predictions and groupthink. Crises are more easily
      recognised and managed where training has covered critical decision methods.

PMID- 29592828
TI  - Improving disaster outcomes with better decision making.
AB  - Decisions made in an emergency can improve or exacerbate the outcome of the
      event. Making complex decisions in high-stress circumstances is not easily done
      without prior training. Understanding how people process information under
      stress, and how decisions are affected by bias, can lead to better decision
      making. This paper examines how risk communication lessons from sense-making
      research and cockpit resource management can be applied to business and industry
      to improve emergency and disaster outcomes.

PMID- 29592829
TI  - Low levels of chemsex among men who have sex with men, but high levels of risk
      among men who engage in chemsex: analysis of a cross-sectional online survey
      across four countries.
AB  - : Background This paper establishes the prevalence of chemsex drug use among men
      who have sex with men (MSM), the extent to which these drugs are used in a sexual
      context, as well as their associated behaviours and circumstances of use.
      METHODS: Data from a cross-sectional, online survey of 2328 MSM recruited via gay
      sociosexual media in Scotland, Wales, Northern Ireland and the Republic of
      Ireland were analysed. RESULTS: While almost half (48.8%) of participants had
      ever taken illicit drugs, lifetime chemsex drug use was less common (18.0%) and
      far fewer reported chemsex drug use in the last year (8.2%) or last 4 weeks
      (3.0%). Just over one-quarter (27.1%) of men who used chemsex drugs in the last
      year reported no sexualised drug use, but almost three-quarters (72.9%) did. Only
      6.1% of the whole sample reported sexualised chemsex drug use in the last year.
      The odds of reporting chemsex in the last year were significantly higher for men
      aged 36-45 years (AOR=1.96), single men (AOR=1.83), men who were HIV positive
      (AOR=4.01), men who report high-risk sex (AOR=4.46), being fisted (AOR=7.77) or
      had sex in exchange for goods other than money (AOR=4.7) in the last year and men
      who reported an HIV test in the last 3 months (AOR=1.53). DISCUSSION: Only a
      small proportion of MSM in Scotland, Wales, Northern Ireland and the Republic of
      Ireland reported chemsex, and, for the first time, it is demonstrated that not
      all chemsex drug use was sexualised. Nevertheless, MSM who engage in chemsex
      (MWEC) reported substantial sexual risk inequalities. These novel findings
      highlight several opportunities for intervention, particularly around the
      multiple vulnerabilities of MWEC, opportunities for early identification of those
      most vulnerable to chemsex-related harm and the potential to develop a
      specialised responsive patient pathway.

PMID- 29592830
TI  - A community-led, harm-reduction approach to chemsex: case study from Australia's
      largest gay city.
AB  - Rates of drug use remain substantially higher among gay and bisexual men (GBM)
      and people living with HIV (PLHIV) in Sydney, New South Wales, Australia. The use
      of drugs to enhance sexual pleasure within cultures of Party and Play creates
      opportunities to discuss sexual health, mental health, consent and wellbeing.
      Community organisations with a history of HIV prevention, care, treatment are
      well-placed to respond. ACON's (formerly the AIDS Council of New South Wales)
      multi-dimensional response to 'chemsex' includes: direct client services support
      for individuals seeking to manage or reduce their use; health promotion
      activities that support peer education; partnerships with research institutions
      to better understand cultures of chemsex; and policy submissions that call for
      drug use to be approached as a health, rather than a criminal, issue. The
      approach speaks the language of Party and Play subcultures; employs culturally
      relevant terminology and imagery; uses content designed, created and delivered by
      peers; and operates within a pleasure-positive, harm-reduction and community-led
      framework. These interventions have led to increased service uptake, strong
      community engagement, robust research partnerships and the recognition of GBM as
      a priority population in relevant strategies.

PMID- 29592831
TI  - True to form-APIC 2018 will deliver!

PMID- 29592832
TI  - Antimicrobial stewardship and infection prevention-leveraging the synergy: A
      position paper update.

PMID- 29592833
TI  - Decreased mortality in patients prescribed vancomycin after implementation of an
      antimicrobial stewardship program.

PMID- 29592835
TI  - Our Educators-Celebrating a Century of the AAOMS.

PMID- 29592834
TI  - Patient compliance with antimicrobial drugs: A Chinese survey.
AB  - BACKGROUND: Antimicrobial therapy is among the mainstream treatment modalities
      employed in clinical settings. Antimicrobial sensitivity of the pathogen and
      patient compliance are key determinants of the efficacy of antimicrobial therapy.
      OBJECTIVE: In this study, we sought to investigate the factors that affect
      patient compliance to antimicrobial therapy in a Chinese teaching hospital to
      enhance patient compliance and to prevent abuse and misuse of antibiotics by
      patients. METHODS: A questionnaire survey was conducted among patients willing to
      answer all the questions who were prescribed antimicrobial drugs orally, and for
      whom at least half of the duration of therapy was not under the supervision of a
      doctor or nurse. Data analyses were performed using Kruskal-Wallis test and
      multivariate logistic regression. RESULTS: A total of 720 patients participated
      in the survey; of these, 714 patients provided complete data and were included in
      the analysis. Up to 86.97% of patients showed noncompliance to antimicrobial
      therapy (total compliance score < 8), whereas 13.03% of patients showed good
      compliance (total compliance score = 8). On multivariate analyses, understanding
      of the treatment was an important factor associated with compliance. CONCLUSIONS:
      A range of factors were associated with compliance to antimicrobial therapy,
      including understanding of the treatment, gender, age, home address, education
      level, and family income.

PMID- 29592836
TI  - The Evolution of Microvascular and Microneurosurgical Maxillofacial
      Reconstruction.

PMID- 29592837
TI  - A proposal for antifungal epidemiological cut-off values against Histoplasma
      capsulatum var. capsulatum based on the susceptibility of isolates from HIV
      infected patients with disseminated histoplasmosis in Northeast Brazil.
AB  - Epidemiological cut-off values (ECVs) have been used as a tool to detect the
      acquisition of resistance mechanisms to antifungal drugs. In this context, the
      objective of this study was to determine the ECVs for classic antifungals against
      Histoplasma capsulatum var. capsulatum isolates from human immunodeficiency virus
      (HIV)-infected patients with a diagnosis of disseminated histoplasmosis. First,
      minimum inhibitory concentrations (MICs) for amphotericin B (AmB), itraconazole
      (ITR), fluconazole (FLU), voriconazole (VCZ) and caspofungin (CAS) were
      determined against 138 H. capsulatum isolates in the filamentous form by the
      broth microdilution method; antifungal ECVs were then calculated. MIC ranges were
      0.0078-1 ug/mL for AmB, 0.0005-0.0625 ug/mL for ITR, 2 to >=256 ug/mL for FLU,
      0.0078-1 ug/mL for VCZ and <=0.0156 to >=32 ug/mL for CAS. The obtained ECVs were
      0.5, 0.0313, 128, 0.5 and 16 ug/mL for AmB, ITR, FLU, VCZ and CAS, respectively.
      The percentage of wild-type isolates was 96.4% for AmB, 98.6% for ITR and 99.3%
      for FLU, VCZ and CAS. Although these results do not cover all phylogenetic
      species of H. capsulatum, they bring important information on strains from
      Brazil. In addition, the assessed isolates were from HIV-positive patients, which
      may not reflect the antifungal ECVs against isolates from immunocompetent
      individuals or from other sources. Finally, this study pioneers the initiative of
      establishing ECVs for five antifungal agents against H. capsulatum var.
      capsulatum, providing a criterion for the interpretation of susceptibility
      results as well as a monitoring strategy for the emergence of antifungal
      resistance.

PMID- 29592838
TI  - Emergence of two Usutu virus lineages in Culex pipiens mosquitoes in the
      Camargue, France, 2015.
AB  - Usutu virus (USUV) was detected in 11 Culex pipiens mosquito pools collected in
      2015 in Camargue (France) using quantitative real-time RT-PCR assays.
      Phylogenetic analysis of recovered virus sequences identified USUV lineages
      Africa 2 and Africa 3, demonstrating the simultaneous occurrence of different
      strains within the mosquito population. This is the first report on USUV in
      mosquitoes from France that concurrently accompanied the emergence of Usutu virus
      in blackbirds and a human case in France during 2015/2016.

PMID- 29592839
TI  - High resolution mass spectrometry-based methodologies for identification of
      Etravirine bioactivation to reactive metabolites: In vitro and in vivo
      approaches.
AB  - Drug bioactivation to reactive metabolites capable of covalent adduct formation
      with bionucleophiles is a major cause of drug-induced adverse reactions.
      Therefore, elucidation of reactive metabolites is essential to unravel the
      toxicity mechanisms induced by drugs and thereby identify patient subgroups at
      higher risk. Etravirine (ETR) was the first second-generation Non-Nucleoside
      Reverse Transcriptase Inhibitor (NNRTI) to be approved, as a therapeutic option
      for HIV-infected patients who developed resistance to the first-generation
      NNRTIs. Additionally, ETR came into market aiming to overcome some adverse
      effects associated with the previously used efavirenz (neurotoxicity) and
      nevirapine (hepatotoxicity) therapies. Nonetheless, post-marketing reports of
      severe ETR-induced skin rash and hypersensitivity reactions have prompted the
      U.S. FDA to issue a safety alert on ETR. Taking into consideration that ETR usage
      may increase in the near future, due to the possible use of the drug for
      coinfection with malaria and HIV, the development of reliable prognostic tools
      for early risk/benefit estimations is urgent. In the current study, high
      resolution mass spectrometry-based methodologies were integrated with MS3
      experiments for the identification of reactive ETR metabolites/adducts: 1) in
      vitro incubation of the drug with human and rat liver S9 fractions in the
      presence of Phase I and II co-factors, including glutathione, as a trapping
      bionucleophile; and 2) in vivo, using urine samples from HIV-infected patients on
      ETR therapy. We obtained evidence for multiple bioactivation pathways leading to
      the formation of covalent adducts with glutathione and N-acetyl-L-cysteine. These
      results suggest that similar reactions may occur with cysteine residues of
      proteins, supporting a role for ETR bioactivation in the onset of the toxic
      effects elicited by the drug. Additionally, ETR metabolites stemming from amine
      oxidation, with potential toxicological significance, were identified in vitro
      and in vivo. Also noteworthy is the fact that new metabolic conjugation pathways
      of glucuronide metabolites were demonstrated for the first time, raising
      questions about their potential toxicological implications. In conclusion, these
      results represent not only a contribution towards the elucidation of new
      metabolic pathways of drugs in general but also an important step towards the
      elucidation of potentially toxic ETR pathways, whose understanding may be crucial
      for reliable risk/benefit estimations of ETR-based regimens.

PMID- 29592841
TI  - Will NNRTIs be driving forward again?

PMID- 29592842
TI  - Mirror Movements are Linked to Executive Control in Healthy and Brain-injured
      Adults.
AB  - It has been shown that brain-injured patients (BIP) have exacerbated mirror
      movements (MM). MM are involuntary contractions occurring in homologous muscles
      contralateral to voluntary movements, particularly in distal upper limb muscles.
      Attentional and inhibitory processes have been proposed as key factors to explain
      the level of MM. However, the link between MM and attentional/inhibitory
      processes has never been formally tested. The present study aims to test this
      link in 24 right-handed healthy adults and eight chronic BIP. We investigated the
      link between the amount/intensity of MM and attentional/inhibitory functions. For
      each participant, MM produced on each limb were assessed with two tasks, and the
      attentional and inhibitory functions were assessed with six neuropsychological
      tests. Our results showed (1) a greater amount and intensity of MM and (2) a
      selective deficit in sustained attention in BIP compared to healthy adults.
      Moreover, (3) in all participants - independent of the type of task used to
      evaluate MM - the amount and intensity of MM was predicted by the level of
      executive control, assessed by the Trail Making Test. High level of MM was
      associated with weak executive control abilities. This study is the first to
      highlight the link between MM and executive functioning, which may have
      implications for rehabilitation in BIP.

PMID- 29592843
TI  - Phosphorylated alpha-Synuclein Accumulations and Lewy Body-like Pathology
      Distributed in Parkinson's Disease-Related Brain Areas of Aged Rhesus Monkeys
      Treated with MPTP.
AB  - Phosphorylation of alpha-synuclein at serine 129 (P-Ser 129 alpha-syn) is
      involved in the pathogenesis of Parkinson's disease (PD) and Lewy body (LB)
      formation. However, there is no clear evidence indicates the quantitative
      relation of P-Ser 129 alpha-syn accumulation and dopaminergic cell loss, LBs
      pathology and the affected brain areas in PD monkeys. Here, pathological changes
      in the substantia nigra (SN) and PD-related brain areas were measured in aged
      monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      utilizing a modeling-recovery-remodeling strategy. Compared to age-matched
      controls, the MPTP-treated monkeys showed significantly reduced tyrosine
      hydroxylase (TH)-positive neurons and increased P-Ser 129 alpha-syn-positive
      aggregations in the SN. Double-labeling Immunofluorescence found some TH-positive
      neurons to be co-localized with P-Ser129 alpha-syn in the SN, suggesting the
      inverse correlation between P-Ser 129 alpha-syn aggregations and dopaminergic
      cell loss in the SN may represent an interactive association related to the
      progression of the PD symptoms in the model. P-Ser 129 alpha-syn aggregations or
      LB-like pathology was also found in the midbrain and the neocortex, specifically
      in the oculomotor nucleus (CN III), temporal cortex (TC), prefrontal cortex (PFC)
      and in cells surrounding the third ventricle. Notably, the occipital cortex (OC)
      was P-Ser 129 alpha-syn negative. The findings of LB-like pathologies,
      dopaminergic cell loss and the stability of the PD symptoms in this model suggest
      that the modeling-recovery-remodeling strategy in aged monkeys may provide a new
      platform for biomedical investigations into the pathogenesis of PD and potential
      therapeutic development.

PMID- 29592840
TI  - Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with
      HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3,
      non-inferiority trial.
AB  - BACKGROUND: Doravirine is a novel non-nucleoside reverse transcriptase inhibitor
      (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent
      in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We
      compared doravirine with ritonavir-boosted darunavir, when both were given with
      two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with
      previously untreated HIV-1 infection. METHODS: In this randomised, controlled,
      double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection
      were screened and enrolled at 125 clinical centres in 15 countries. Eligible
      participants (aged >=18 years) were naive to antiretroviral therapy with plasma
      HIV-1 RNA of at least 1000 copies per mL at screening. Participants who had
      previously been treated for a viral infection other than HIV-1, those taking
      immunosuppressive drugs, and individuals with active acute hepatitis were
      excluded. Participants were randomly assigned (1:1) via an interactive voice and
      web response system to receive oral doravirine 100 mg or darunavir 800 mg plus
      ritonavir 100 mg once daily, with two investigator-selected NRTIs (tenofovir and
      emtricitabine or abacavir and lamivudine) for up to 96 weeks. Randomisation was
      stratified by HIV-1 RNA measurements at screening (<=100 000 vs >100 000 copies
      per mL) and the NRTI pair. Study participants, funding institution staff,
      investigators, and study site personnel were masked to treatment group
      assignment. The primary efficacy endpoint was the proportion of participants
      achieving HIV-1 RNA of less than 50 copies per mL at week 48 defined by the US
      Food and Drug Administration snapshot algorithm, with non-inferiority established
      if the lower bound of the two-sided 95% CI for the treatment difference
      (doravirine minus darunavir) was greater than -10 percentage points. All
      participants who received at least one dose of study drug were included in the
      primary efficacy and safety analyses. This trial is active, but not recruiting,
      and is registered with ClinicalTrials.gov, number NCT02275780. FINDINGS: Between
      Dec 1, 2014, and Oct 20, 2015, 1027 participants were screened for eligibility,
      of whom 769 participants were randomly assigned to treatment (385 with doravirine
      and 384 with ritonavir-boosted darunavir). 56 participants discontinued treatment
      in the doravirine group compared with 71 in the darunavir group, mostly due to
      loss to follow-up. 383 participants who received doravirine and 383 who received
      darunavir were included in the primary efficacy analyses. At week 48, 321 (84%)
      participants in the doravirine group and 306 (80%) in the darunavir group
      achieved plasma HIV-1 RNA of less than 50 copies per mL (difference 3.9%, 95% CI 
      1.6 to 9.4), indicating non-inferiority of the doravirine regimen. The most
      common study drug-related adverse events were diarrhoea (21 [5%] of 383
      participants in the doravirine group and 49 [13%] of 383 participants in the
      darunavir group), nausea (25 [7%] vs 29 [8%]), and headache (23 [6%] vs ten
      [3%]). 18 participants (six [2%] of 383 participants in the doravirine group vs
      12 [3%] of 383 participants in the darunavir group) discontinued treatment due to
      adverse events, which were considered drug-related in four (1%) participants in
      the doravirine group and 8 (2%) participants in the darunavir group. Serious
      adverse events occurred in 19 (5%) of 383 participants in the doravirine group
      and 23 (6%) of 383 in the darunavir roup, and were considered study-drug related
      in one (<1%) participant of each group. INTERPRETATION: In treatment-naive adults
      with HIV-1 infection, doravirine combined with two NRTIs might offer a valuable
      treatment option for adults with previously untreated HIV-1 infection. FUNDING:
      Merck & Co.

PMID- 29592844
TI  - Anti-oxidative and Anti-apoptotic Effects of Acupuncture: Role of Thioredoxin-1
      in the Hippocampus of Vascular Dementia Rats.
AB  - Emerging evidence suggests that acupuncture treatment has anti-oxidative effects
      that affect cognitive impairment in vascular dementia (VD) rats. In the present
      study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin
      reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After
      2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE)
      staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining
      were used to assess the effects of acupuncture on cognitive function and
      hippocampal neuronal injury in two-vessel occlusion (2VO) model. The protein and
      mRNA levels of Trx-1 and TrxR-1, the activity of TrxR-1 as well as the
      phosphorylation of the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N
      terminal kinase (JNK)/p38 pathway were measured by Western blot, real-time PCR
      analysis, TrxR-1 activity analysis and immunofluorescence (IF) staining
      respectively. We found that there were oxidative and apoptotic injury in the CA1
      area, accompanied with the decreased expressions of Trx-1 and TrxR-1 in the
      hippocampus. Acupuncture ameliorated cognitive deficits caused by cerebral
      ischemic injury and inhibited oxidative stress and neuronal apoptotic injury in
      the hippocampus. Acupuncture also up-regulated the expressions of Trx-1 and TrxR
      1, increased the activity of TrxR-1, accompanied with inhibiting the activation
      of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving
      cognitive function, inhibiting oxidative stress and neuron apoptotic damage were
      blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture
      treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which
      involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38
      pathway.

PMID- 29592845
TI  - Use of Social Network Sites for Communication Among Health Professionals:
      Systematic Review.
AB  - BACKGROUND: Although much research has been done investigating the roles of
      social network sites (SNSs) in linking patients and health professionals, there
      is a lack of information about their uses, benefits, and limitations in
      connecting health professions only for professional communication. OBJECTIVE:
      This review aimed to examine the utilization of SNSs for communication among
      health professionals in (1) frontline clinical practice, (2) professional
      networks, and (3) education and training to identify areas for future health
      communication research. METHODS: This review followed the Preferred Reporting
      Items for Systematic Reviews and Meta-analyses guidelines. A systematic search of
      the literature published in the last 10 years (January 1, 2007, to March 1, 2017)
      was performed in March 2017, using the following electronic databases: MEDLINE
      via OvidSP, EMBASE, CINAHL Complete, and InfoSci-Journals. The searches were
      conducted using the following defined search terms: "social media" OR "social
      network" OR "social network site" OR "Facebook" OR "Twitter" OR "Linkedin" OR
      "Instagram" OR "Weibo" OR "Whatsapp" OR "Telegram" OR "WeChat" AND "health" OR
      "health profession." RESULTS: Of the 6977 papers retrieved, a total of 33 studies
      were included in this review. They were exploratory in nature, and the majority
      used surveys (n=25) and interviews (n=6). All retrieved studies stated that SNSs
      enhanced effective communication and information sharing. SNSs were used for
      supporting delivering of clinical services, making referrals, and sharing
      information. They were beneficial to network building and professional
      collaboration. SNSs were novel tools to enhance educational interactions among
      peers, students, instructors, and preceptors. The application of SNSs came with
      restraints in technical knowledge, concerns on data protection, privacy and
      liability, issues in professionalism, and data protection. CONCLUSIONS: SNSs
      provide platforms facilitating efficient communication, interactions, and
      connections among health professionals in frontline clinical practice,
      professional networks, education, and training with limitations identified as
      technical knowledge, professionalism, and risks of data protection. The evolving
      use of SNSs necessitates robust research to explore the full potential and the
      relative effectiveness of SNSs in professional communication.

PMID- 29592846
TI  - Evaluating an mHealth App for Health and Well-Being at Work: Mixed-Method
      Qualitative Study.
AB  - BACKGROUND: To improve workers' health and well-being, workplace interventions
      have been developed, but utilization and reach are unsatisfactory, and effects
      are small. In recent years, new approaches such as mobile health (mHealth) apps
      are being developed, but the evidence base is poor. Research is needed to examine
      its potential and to assess when, where, and for whom mHealth is efficacious in
      the occupational setting. To develop interventions for workers that actually will
      be adopted, insight into user satisfaction and technology acceptance is
      necessary. For this purpose, various qualitative evaluation methods are
      available. OBJECTIVE: The objectives of this study were to gain insight into (1)
      the opinions and experiences of employees and experts on drivers and barriers
      using an mHealth app in the working context and (2) the added value of three
      different qualitative methods that are available to evaluate mHealth apps in a
      working context: interviews with employees, focus groups with employees, and a
      focus group with experts. METHODS: Employees of a high-tech company and experts
      were asked to use an mHealth app for at least 3 weeks before participating in a
      qualitative evaluation. Twenty-two employees participated in interviews, 15
      employees participated in three focus groups, and 6 experts participated in one
      focus group. Two researchers independently coded, categorized, and analyzed all
      quotes yielded from these evaluation methods with a codebook using constructs
      from user satisfaction and technology acceptance theories. RESULTS: Interviewing
      employees yielded 785 quotes, focus groups with employees yielded 266 quotes, and
      the focus group with experts yielded 132 quotes. Overall, participants muted
      enthusiasm about the app. Combined results from the three evaluation methods
      showed drivers and barriers for technology, user characteristics, context,
      privacy, and autonomy. A comparison between the three qualitative methods showed
      that issues revealed by experts only slightly overlapped with those expressed by
      employees. In addition, it was seen that the type of evaluation yielded different
      results. CONCLUSIONS: Findings from this study provide the following
      recommendations for organizations that are planning to provide mHealth apps to
      their workers and for developers of mHealth apps: (1) system performance
      influences adoption and adherence, (2) relevancy and benefits of the mHealth app
      should be clear to the user and should address users' characteristics, (3) app
      should take into account the work context, and (4) employees should be alerted to
      their right to privacy and use of personal data. Furthermore, a qualitative
      evaluation of mHealth apps in a work setting might benefit from combining more
      than one method. Factors to consider when selecting a qualitative research method
      are the design, development stage, and implementation of the app; the working
      context in which it is being used; employees' mental models; practicability;
      resources; and skills required of experts and users.

PMID- 29592847
TI  - Investigating the Extent to Which Patients Should Control Access to Patient
      Records for Research: A Deliberative Process Using Citizens' Juries.
AB  - BACKGROUND: The secondary use of health data for research raises complex
      questions of privacy and governance. Such questions are ill-suited to opinion
      polling where citizens must choose quickly between multiple-choice answers based
      on little information. OBJECTIVE: The aim of this project was to extend knowledge
      about what control informed citizens would seek over the use of health records
      for research after participating in a deliberative process using citizens'
      juries. METHODS: Two 3-day citizens' juries, of 17 citizens each, were convened
      to reflect UK national demographics from 355 eligible applicants. Each jury
      addressed the mission "To what extent should patients control access to patient
      records for secondary use?" Jurors heard from and questioned 5 expert witnesses
      (chosen either to inform the jury, or to argue for and against the secondary use
      of data), interspersed with structured opportunities to deliberate among
      themselves, including discussion and role-play. Jurors voted on a series of
      questions associated with the jury mission, giving their rationale. Individual
      views were polled using questionnaires at the beginning and at end of the
      process. RESULTS: At the end of the process, 33 out of 34 jurors voted in support
      of the secondary use of data for research, with 24 wanting individuals to be able
      to opt out, 6 favoring opt in, and 3 voting that all records should be available
      without any consent process. When considering who should get access to data, both
      juries had very similar rationales. Both thought that public benefit was a key
      justification for access. Jury 1 was more strongly supportive of sharing patient
      records for public benefit, whereas jury 2 was more cautious and sought to give
      patients more control. Many jurors changed their opinion about who should get
      access to health records: 17 people became more willing to support wider
      information sharing of health data for public benefit, whereas 2 moved toward
      more patient control over patient records. CONCLUSIONS: The findings highlight
      that, when informed of both risks and opportunities associated with data sharing,
      citizens believe an individual's right to privacy should not prevent research
      that can benefit the general public. The juries also concluded that patients
      should be notified of any such scheme and have the right to opt out if they so
      choose. Many jurors changed their minds about this complex policy question when
      they became more informed. Many, but not all, jurors became less skeptical about
      health data sharing, as they became better informed of its benefits and risks.

PMID- 29592848
TI  - Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review
      and Content Analysis Using the Mobile App Rating Scale (MARS).
AB  - BACKGROUND: General consumers can now easily access drug information and quickly
      check for potential drug-drug interactions (PDDIs) through mobile health
      (mHealth) apps. With aging population in Canada, more people have chronic
      diseases and comorbidities leading to increasing numbers of medications. The use
      of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and
      empowerment. OBJECTIVE: The aim of this study was to review the characteristics
      and quality of publicly available mHealth apps that check for PDDIs. METHODS:
      Apple App Store and Google Play were searched to identify apps with PDDI
      functionality. The apps' general and feature characteristics were extracted. The
      Mobile App Rating Scale (MARS) was used to assess the quality. RESULTS: A total
      of 23 apps were included for the review-12 from Apple App Store and 11 from
      Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD.
      The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS
      scores for the apps from Google Play and Apple App Store were not statistically
      different (P=.84). The information dimension was associated with the highest
      score (3.63), whereas the engagement dimension resulted in the lowest score
      (2.75). The total number of features per app, average rating, and price were
      significantly associated with the total MARS score. CONCLUSIONS: Some apps
      provided accurate and comprehensive information about potential adverse drug
      effects from PDDIs. Given the potentially severe consequences of incorrect drug
      information, there is a need for oversight to eliminate low quality and
      potentially harmful apps. Because managing PDDIs is complex in the absence of
      complete information, secondary features such as medication reminder, refill
      reminder, medication history tracking, and pill identification could help enhance
      the effectiveness of PDDI apps.

PMID- 29592850
TI  - Doctors should advise smokers on using e-cigarettes, says NICE.

PMID- 29592849
TI  - Online Health Monitoring using Facebook Advertisement Audience Estimates in the
      United States: Evaluation Study.
AB  - BACKGROUND: Facebook, the most popular social network with over one billion daily
      users, provides rich opportunities for its use in the health domain. Though much
      of Facebook's data are not available to outsiders, the company provides a tool
      for estimating the audience of Facebook advertisements, which includes aggregated
      information on the demographics and interests, such as weight loss or dieting, of
      Facebook users. This paper explores the potential uses of Facebook ad audience
      estimates for eHealth by studying the following: (1) for what type of health
      conditions prevalence estimates can be obtained via social media and (2) what
      type of marker interests are useful in obtaining such estimates, which can then
      be used for recruitment within online health interventions. OBJECTIVE: The
      objective of this study was to understand the limitations and capabilities of
      using Facebook ad audience estimates for public health monitoring and as a
      recruitment tool for eHealth interventions. METHODS: We use the Facebook
      Marketing application programming interface to correlate estimated sizes of
      audiences having health-related interests with public health data. Using several
      study cases, we identify both potential benefits and challenges in using this
      tool. RESULTS: We find several limitations in using Facebook ad audience
      estimates, for example, using placebo interest estimates to control for
      background level of user activity on the platform. Some Facebook interests such
      as plus-size clothing show encouraging levels of correlation (r=.74) across the
      50 US states; however, we also sometimes find substantial correlations with the
      placebo interests such as r=.68 between interest in Technology and Obesity
      prevalence. Furthermore, we find demographic-specific peculiarities in the
      interests on health-related topics. CONCLUSIONS: Facebook's advertising platform
      provides aggregate data for more than 190 million US adults. We show how disease
      specific marker interests can be used to model prevalence rates in a simple and
      intuitive manner. However, we also illustrate that building effective marker
      interests involves some trial-and-error, as many details about Facebook's black
      box remain opaque.

PMID- 29592852
TI  - Professional judgment v customer expectations.

PMID- 29592851
TI  - Development of a provisional essential medicines list for children in Canada:
      consensus process.
AB  - BACKGROUND: Worldwide, many countries have developed a list of essential
      medicines for children to improve prescribing. We aimed to create an essential
      medicines list for children in Canada. METHODS: We adapted the previously created
      preliminary list of essential medicines for adults in Canada and the WHO Model
      List of Essential Medicines for Children to create a provisional list of
      essential medicines for children in Canada. Canadian clinicians made suggestions
      for changes. Literature relevant to each suggestion was presented to clinician
      scientists, who used a modified nominal group technique to make recommendations
      on the suggestions. Ontario Public Drug Programs prescription data were reviewed
      to identify commonly prescribed medications missing from the list. Literature
      relevant to these medications was shared with a clinician-scientist review panel
      to determine which should be added, and a revised list was developed. RESULTS: A
      total of 76 items were removed from the list of essential medicines for adults in
      Canada because they were not indicated for use in children or were not relevant
      in the Canadian health care context; 7 medications were added to the child list
      based on Ontario Public Drugs Programs prescribing data and clinician-scientist
      review. Suggestions to add, remove or substitute medications were made by peer
      reviewers and resulted in removal of 1 medication and replacement of 1
      medication. The process produced a provisional list of 67 essential medications
      for children. INTERPRETATION: A provisional list of 67 essential medicines for
      children was created through a peer-reviewed, multistep process based on current
      clinical evidence, Canadian clinical practice guidelines and historical
      prescribing data. It is publicly posted at http://cleanmeds.ca/. The list should
      be further developed based on wider input and should be continuously revised
      based on emerging evidence of the safety and effectiveness of these medicines in
      all pediatric age groups.

PMID- 29592853
TI  - Doctors criticise India's "ill conceived" launch of publicly funded health
      insurance scheme.

PMID- 29592854
TI  - Hard truths: pictures of crisis and conflict.

PMID- 29592857
TI  - Tim Briggs: GIRFT, that's the main thing.

PMID- 29592856
TI  - The BMJ Awards 2018: Clinical Leadership.

PMID- 29592858
TI  - Immuno-modulatory effect of local rhEGF treatment during tissue repair in
      diabetic ulcers.
AB  - Wound healing is a complex process that can be severely impaired due to
      pathological situations such as diabetes mellitus. Diabetic foot ulcers are a
      common complication of this pathology and are characterized by an excessive
      inflammatory response. In this work, the effects of local treatment with
      recombinant human epidermal growth factor (rhEGF) were studied using a full
      thickness wound healing model in streptozotocin-induced diabetic rats. Wound
      healing process was assessed with different concentrations of rhEGF (0.1, 0.5,
      2.0 and 8.0 ug/mL), placebo and both diabetic and non-diabetic controls (n = 53).
      The macroscopic healing observed in treated diabetic rats was affected by rhEGF
      concentration. Histologically, we also observed an improvement in the
      epithelialization, granulation tissue formation and maturation in treated groups,
      finding again the best response at doses of 0.5 and 2.0 ug/mL. Afterwards, the
      tissue immune response over time was assessed in diabetic rats using the most
      effective concentrations of rhEGF (0.5 and 2.0 ug/mL), compared to controls. The
      presence of macrophages, CD4+ T lymphocytes and CD8+ T lymphocytes, in the
      reparative tissue was quantified, and cytokine expression was measured by
      quantitative real-time PCR. rhEGF treatment caused a reduction in the number of
      infiltrating macrophages in the healing tissue of diabetic, as well as diminished
      activation of these leukocytes. These findings show that local administration of
      rhEGF improves the healing process of excisional wounds and the quality of the
      neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the
      local inflammation associated with diabetic healing, indicating immuno-modulatory
      properties.

PMID- 29592860
TI  - Extended visitation policy may lower risk for delirium in the intensive care
      unit.

PMID- 29592859
TI  - Stress granules counteract senescence by sequestration of PAI-1.
AB  - Cellular senescence is a physiological response by which an organism halts the
      proliferation of potentially harmful and damaged cells. However, the accumulation
      of senescent cells over time can become deleterious leading to diseases and
      physiological decline. Our data reveal a novel interplay between senescence and
      the stress response that affects both the progression of senescence and the
      behavior of senescent cells. We show that constitutive exposure to stress induces
      the formation of stress granules (SGs) in proliferative and presenescent cells,
      but not in fully senescent cells. Stress granule assembly alone is sufficient to
      decrease the number of senescent cells without affecting the expression of bona
      fide senescence markers. SG-mediated inhibition of senescence is associated with
      the recruitment of the plasminogen activator inhibitor-1 (PAI-1), a known
      promoter of senescence, to these entities. PAI-1 localization to SGs increases
      the translocation of cyclin D1 to the nucleus, promotes RB phosphorylation, and
      maintains a proliferative, non-senescent state. Together, our data indicate that
      SGs may be targets of intervention to modulate senescence in order to impair or
      prevent its deleterious effects.

PMID- 29592861
TI  - Pharmacological treatment reduces the risk of motor vehicle crashes among men and
      women with ADHD.

PMID- 29592862
TI  - The Role of Trehalose 6-Phosphate in Crop Yield and Resilience.

PMID- 29592863
TI  - Cadmium in tobacco smokers: a neglected link to lung disease?
AB  - Cadmium in tobacco smoke may contribute to the development of pulmonary
      emphysema. However, there is poor understanding of the mechanisms behind the
      pathogenic role of cadmium in this and other smoking-related lung diseases. The
      traditional focus on the total body burden of cadmium, estimated through analysis
      of urine, may not fully reflect the local burden of cadmium, since it is inhaled
      by smokers. Thus, assessing the local accumulation of cadmium in the lungs
      appears more relevant, given that there is tissue-specific retention of
      cadmium.In this review, we outline the principal sources of cadmium exposure and
      the clinical effects of occupational exposure. In addition, we review evidence on
      local cadmium and its association with alterations in innate immunity in tobacco
      smokers. Moreover, we scrutinise the data on cadmium as a cause of lung disease
      in translational models.We conclude that cadmium may contribute to smoking
      related lung diseases, possibly via an altered redox balance and by making
      macrophages dysfunctional. However, there is a need for new studies on local
      cadmium levels and their relation to pathology in long-term tobacco smokers, as
      well as for more in-depth studies on cellular and molecular mechanisms, to
      elucidate the importance of cadmium in smoking-related lung diseases.

PMID- 29592864
TI  - Personalised pulmonary rehabilitation in COPD.
AB  - This review summarises ongoing developments in personalised medicine and
      individualised medicine in chronic obstructive pulmonary disease (COPD).
      Currently applied classification systems largely ignore the complexity and
      heterogeneity of the COPD syndrome. Personalised medicine has to consider the
      influence of unique circumstances of the person, which contribute to this
      heterogeneity and complexity. Pulmonary rehabilitation is described as a
      comprehensive, individualised intervention based on thorough assessment of
      identifiable treatable traits. Partnership in care will become a crucial factor
      to improve and maintain health. Tolerating uncertainty and unpredictability will
      enrich future doctor-patient relationships.

PMID- 29592865
TI  - Survey of management of iatrogenic bleeding following bronchoscopic sampling.

PMID- 29592866
TI  - Highlights in acute respiratory failure.

PMID- 29592867
TI  - Periprostatic fat tissue transcriptome reveals a signature diagnostic for high
      risk prostate cancer.
AB  - Evidence suggests that altered adipose tissue homeostasis may be an important
      contributor to the development and/or progression of prostate cancer. In this
      study, we investigated the adipose transcriptional profiles of low- and high-risk
      disease to determine both prognostic potential and possible biological drivers of
      aggressive disease. RNA was extracted from periprostatic adipose tissue from
      patients categorised as having prostate cancer with either a low or high risk of
      progression based on tumour characteristics at prostatectomy and profiled by RNA
      sequencing. The expression of selected genes was then quantified by qRT-PCR in a
      cross-validation cohort. In the first phase, a total of 677 differentially
      transcribed genes were identified, from which a subset of 14 genes was
      shortlisted. In the second phase, a 3 gene (IGHA1, OLFM4, RERGL) signature was
      refined and evaluated using recursive feature selection and cross-validation,
      obtaining a promising discriminatory utility (area under curve 0.72) at
      predicting the presence of high-risk disease. Genes implicated in immune and/or
      inflammatory responses predominated. Periprostatic adipose tissue from patients
      with high-risk prostate cancer has a distinct transcriptional signature that may
      be useful for detecting its occult presence. Differential expression appears to
      be driven by a local immune/inflammatory reaction to more advanced tumours, than
      any specific adipose tissue-specific tumour-promoting mechanism. This signature
      is transferable into a clinically usable PCR-based assay, which in a cross
      validation cohort shows diagnostic potential.

PMID- 29592868
TI  - Ki67 proliferative index of the neuroendocrine component drives MANEC prognosis.
AB  - Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly
      differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC)
      neoplastic epithelial component, each representing at least 30% of the tumor. At
      present, prognostic factors for MANECs remain largely unexplored. We investigated
      the clinical-pathologic features of a large multicenter series of digestive
      system MANECs. Surgical specimens of 200 MANEC candidates were centrally
      reviewed; diagnosis was confirmed in 160 cases. While morphology, proliferation
      (mitotic count (MC), Ki67 index) and immunophenotype (p53, SSTR2a, beta-Catenin,
      Bcl-2, p16, Rb1, ALDH, mismatch repair proteins and CD117) were investigated
      separately in both components, genomic (TP53, KRAS, BRAF) alterations were
      searched for on the entire tumor. Data were correlated with overall survival
      (OS). MANEC sites were: 92 colorectal, 44 gastroesophageal and 24
      pancreatobiliary. Median OS was 13.2 months. After adjustment for primary site,
      Ki67 index of the NEC component (but not of the non-NEC component) was the most
      powerful prognostic marker. At multivariable analysis, patients with Ki67 >= 55%
      had an 8-fold risk of death (hazard ratio (HR) 7.83; 95% confidence interval (CI)
      4.17-14.7; P < 0.0001) and a median OS of 12.2 months compared to those with Ki67
      < 55% (median OS 40.5 months). MC (HR 1.51; 95% CI 1.03-2.20, P = 0.04) was a
      weaker prognostic index. Colorectal primary site (HR 1.60; 95% CI 1.11-2.32; P =
      0.01) was significantly associated with poorer survival. No single immunomarker,
      in either component, was statistically significant. This retrospective analysis
      of a large series of digestive system MANECs, showed that the NEC component,
      particularly its Ki67 index, was the main prognostic driver.

PMID- 29592869
TI  - A Summer Nutrition Benefit Pilot Program and Low-income Children's Food Security.
AB  - BACKGROUND: Federal summer meals programs serve less than one-sixth of children
      that receive free or reduced-price meals during the school year. To address this
      gap in food assistance for school-aged children, the Summer Electronic Benefits
      Transfer for Children (SEBTC) Demonstrations provided summer food assistance in
      the form of electronic benefits transfer cards to households with school-aged
      children certified for free or reduced-price meals during the school year.
      METHODS: Over 2011-2013, the SEBTC demonstrations were evaluated by using a
      random assignment design. Households were randomly assigned a monthly $60-per
      child benefit, a monthly $30-per-child benefit, or no benefit, depending on the
      study year. Key outcomes included children's food security and consumption of
      foods and food groups related to a healthful diet (diet quality). At baseline (in
      the spring) and again in the summer, the evaluation surveyed ~52 000 households
      over the course of the 3 years of the impact study. RESULTS: SEBTC reduced the
      prevalence of very low food security among children by one-third. It also had
      positive impacts on 6 of the 8 child nutrition outcomes measured (amounts of
      fruits and vegetables; whole grains; dairy foods; and added sugars). CONCLUSIONS:
      SEBTC is a promising model to improve food security and the dietary quality of
      low-income school-aged children in the summer months.

PMID- 29592870
TI  - What a Summer Nutrition Benefit Program Could Mean for Clinicians and Their
      Patients.

PMID- 29592871
TI  - Cystathionine beta-lyase is involved in d-amino acid metabolism.
AB  - Non-canonical d-amino acids play important roles in bacteria including control of
      peptidoglycan metabolism and biofilm disassembly. Bacteria appear to produce non
      canonical d-amino acids to adapt to various environmental changes, and
      understanding the biosynthetic pathways is important. We identified novel amino
      acid racemases possessing the ability to produce non-canonical d-amino acids in
      Escherichia coli and Bacillus subtilis in our previous study, whereas the
      biosynthetic pathways of these d-amino acids still remain unclear. In the present
      study, we demonstrated that two cystathionine beta-lyases (MetC and MalY) from E.
      coli produce non-canonical d-amino acids including non-proteinogenic amino acids.
      Furthermore, MetC displayed d- and l-serine (Ser) dehydratase activity. We
      characterised amino acid racemase, Ser dehydratase and cysteine lyase activities,
      and all were higher for MetC. Interestingly, all three activities were at a
      comparable level for MetC, although optimal conditions for each reaction were
      distinct. These results indicate that MetC and MalY are multifunctional enzymes
      involved in l-methionine metabolism and the production of d-amino acids, as well
      as d- and l-Ser metabolism. To our knowledge, this is the first evidence that
      cystathionine beta-lyase is a multifunctional enzyme with three different
      activities.

PMID- 29592872
TI  - The long non-coding RNA SNHG5 regulates gefitinib resistance in lung
      adenocarcinoma cells by targetting miR-377/CASP1 axis.
AB  - Gefitinib resistance is one of the major obstacles for the treatment of lung
      adenocarcinoma (LAD). The present study aimed to investigate the effects of the
      long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib
      resistance in LAD and explore the underlying mechanisms. The quantitative real
      time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down
      regulated in LAD patients with acquired gefitinib resistance and gefitinib
      resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD
      cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib
      sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that
      SNHG5 exerted its function through interaction with miR-377, which was further
      confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5
      suppressed the expression of miR-377, while the knockdown of SNHG5 increased the
      miR-377 expression. MiR-377 expression was significantly up-regulated in LAD
      specimens with acquired gefitinib resistance and was negatively correlated with
      SNHG5 expression. In addition, CASP1 was predicted as a downstream target of miR
      377 Overexpression of miR-377 suppressed the expression of CASP1 in PC9 cells and
      knockdown of miR-377 increased the CASP1 expression in PC9GR cells. In vitro
      functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR
      cells abolished their gefitinib resistance. Overall, the present study
      demonstrated, for the first time, that the SNHG5/miR-377/CASP1 axis functions as
      an important role in LAD cells gefitinib resistance and potentially contributes
      to the improvement of LAD diagnosis and therapy.

PMID- 29592873
TI  - Atorvastatin ameliorates early brain injury through inhibition of apoptosis and
      ER stress in a rat model of subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with
      very poor prognosis. The aim of the present study was to evaluate the protective
      effects of atorvastatin on early brain injury (EBI) after SAH using a perforation
      SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the
      sham group, the SAH group (model group), SAH + 10 mg.kg-1day-1 atorvastatin (low
      atorvastatin group), and SAH + 20 mg.kg-1day-1 atorvastatin (high atorvastatin
      group). Atorvastatin was administered orally by gastric gavage for 15 days before
      operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain
      water content, apoptosis by TUNEL assay and scanning electron microscope (SEM),
      and the expression of apoptosis-related proteins by immunofluorescence and
      Western blotting analysis. Compared with the sham group, we observed increased
      brain water content, significant apoptosis, and elevated levels of apoptosis
      related proteins including caspase-3, CCAAT enhancer-binding protein homologous
      protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4
      (AQP4) in the SAH group. Atorvastatin administration under all doses could
      significantly reduce brain water content, apoptosis, and the expression levels of
      caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early
      treatment with atorvastatin effectively ameliorates EBI after SAH through anti
      apoptotic effects and the effects might be associated inhibition of caspase-3 and
      endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

PMID- 29592875
TI  - Selectins and chemokines use shared and distinct signals to activate beta2
      integrins in neutrophils.
AB  - Rolling neutrophils receive signals while engaging P- and E-selectin and
      chemokines on inflamed endothelium. Selectin signaling activates beta2 integrins
      to slow rolling velocities. Chemokine signaling activates beta2 integrins to
      cause arrest. Despite extensive study, key aspects of these signaling cascades
      remain unresolved. Using complementary in vitro and in vivo assays, we found that
      selectin and chemokine signals in neutrophils triggered Rap1a-dependent and
      phosphatidylinositol-4-phosphate 5-kinase gamma (PIP5Kgamma90)-dependent pathways
      that induce integrin-dependent slow rolling and arrest. Interruption of both
      pathways, but not either pathway alone, blocked talin-1 recruitment to and
      activation of integrins. An isoform of PIP5Kgamma90 lacking the talin-binding
      domain (PIP5Kgamma87) could not activate integrins. Chemokines, but not
      selectins, used phosphatidylinositol-4,5-bisphosphate 3-kinase gamma (PI3Kgamma)
      in cooperation with Rap1a to mediate integrin-dependent slow rolling (at low
      chemokine concentrations), as well as arrest (at high chemokine concentrations).
      High levels of chemokines activated beta2 integrins without selectin signals.
      When chemokines were limiting, they synergized with selectins to activate beta2
      integrins.

PMID- 29592874
TI  - Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.
AB  - Recognition of dsRNA molecules activates the MDA5-MAVS pathway and plays a
      critical role in stimulating type-I interferon responses in psoriasis. However,
      the source of the dsRNA accumulation in psoriatic keratinocytes remains largely
      unknown. A-to-I RNA editing is a common co- or post-transcriptional modification
      that diversifies adenosine in dsRNA, and leads to unwinding of dsRNA structures.
      Thus, impaired RNA editing activity can result in an increased load of endogenous
      dsRNAs. Here we provide a transcriptome-wide analysis of RNA editing across
      dozens of psoriasis patients, and we demonstrate a global editing reduction in
      psoriatic lesions. In addition to the global alteration, we also detect editing
      changes in functional recoding sites located in the IGFBP7, COPA, and FLNA genes.
      Accretion of dsRNA activates autoimmune responses, and therefore the results
      presented here, linking for the first time an autoimmune disease to reduction in
      global editing level, are relevant to a wide range of autoimmune diseases.

PMID- 29592876
TI  - Third-party fecal microbiota transplantation following allo-HCT reconstitutes
      microbiome diversity.
AB  - We hypothesized that third-party fecal microbiota transplantation (FMT) may
      restore intestinal microbiome diversity after allogeneic hematopoietic cell
      transplantation (allo-HCT). In this open-label single-group pilot study, 18
      subjects were enrolled before allo-HCT and planned to receive third-party FMT
      capsules. FMT capsules were administered no later than 4 weeks after neutrophil
      engraftment, and antibiotics were not allowed within 48 hours before FMT. Five
      patients did not receive FMT because of the development of early acute
      gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3),
      persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1).
      Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after
      HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the
      primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment
      related significant adverse event (abdominal pain). Two patients subsequently
      developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No
      additional cases of bacteremia occurred. Median follow-up for survivors is 15
      months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall
      survival and progression-free survival after FMT were 85% (95% confidence
      interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively.
      There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse
      mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition
      and urine 3-indoxyl sulfate concentration indicated improvement in intestinal
      microbiome diversity after FMT that was associated with expansion of stool-donor
      taxa. These results indicate that empiric third-party FMT after allo-HCT appears
      to be feasible, safe, and associated with expansion of recipient microbiome
      diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.

PMID- 29592877
TI  - Analysis of HSP27 and the Autophagy Marker LC3B+ Puncta Following Preoperative
      Chemotherapy Identifies High-Risk Osteosarcoma Patients.
AB  - Chemotherapy-induced autophagy is a proposed mechanism of chemoresistance and
      potential therapeutic target in osteosarcoma. We evaluated heat shock protein 27
      (HSP27) and autophagy-related proteins as predictors of pathologic treatment
      response and prognostic markers among osteosarcoma patients who received standard
      chemotherapy. We analyzed 394 tumor specimens (pre-treatment, post-treatment, and
      metastases) from 260 osteosarcoma patients by immunohistochemistry for
      cytoplasmic light chain 3B (LC3B)-positive puncta, sequestosome 1 (SQSTM1), high
      mobility group box 1 (HMGB1), and HSP27 expression. The staining percentage and
      intensity for each marker were scored and the extent to which marker expression
      was correlated with pathologic response, relapse-free survival (RFS), and overall
      survival (OS) was assessed. LCB3+ puncta in post-treatment primary tumors (50%)
      and metastases (67%) was significantly higher than in pre-treatment biopsy
      specimens (30%; P = 0.023 and <0.001). Among 215 patients with localized
      osteosarcoma, both pre-treatment [multivariate hazard ratio (HR), 26.7; 95%
      confidence interval (CI), 1.47-484; P = 0.026] and post-treatment HSP27
      expression (multivariate HR, 1.85; 95% CI, 1.03-3.33; P = 0.039) were associated
      with worse OS. Lack of LC3B+ puncta at resection was an independent poor
      prognostic marker in both univariate (HR, 1.78; 95% CI, 1.05-3.03; P = 0.034) and
      multivariate models (HR, 1.75; 95% CI, 1.01-3.04; P = 0.045). Patients with
      LC3B+/HSP27- tumors at resection had the best 10-year OS (75%) whereas patients
      with LC3B-/HSP27+ tumors had the worst 10-year survival (25%). Neither HSP27
      expression nor the presence of LCB3+ puncta was correlated with pathologic
      treatment response. Our findings establish HSP27 expression and LC3B+ puncta as
      independent prognostic markers in osteosarcoma patients receiving standard
      chemotherapy and support further investigation into strategies targeting HSP27 or
      modulating autophagy in osteosarcoma treatment. Mol Cancer Ther; 17(6); 1315-23.
      (c)2018 AACR.

PMID- 29592878
TI  - Nuclear Factor-kappaB Promotes Urothelial Tumorigenesis and Cancer Progression
      via Cooperation with Androgen Receptor Signaling.
AB  - We investigated the role of NF-kappaB in the development and progression of
      urothelial cancer as well as cross-talk between NF-kappaB and androgen receptor
      (AR) signals in urothelial cells. Immunohistochemistry in surgical specimens
      showed that the expression levels of NF-kappaB/p65 (P = 0.015)/phospho-NF
      kappaB/p65 (P < 0.001) were significantly elevated in bladder tumors, compared
      with those in nonneoplastic urothelial tissues. The rates of phospho-NF
      kappaB/p65 positivity were also significantly higher in high-grade (P =
      0.015)/muscle-invasive (P = 0.033) tumors than in lower grade/non-muscle-invasive
      tumors. Additionally, patients with phospho-NF-kappaB/p65-positive muscle
      invasive bladder cancer had significantly higher risks of disease progression (P
      < 0.001) and cancer-specific mortality (P = 0.002). In immortalized human normal
      urothelial SVHUC cells stably expressing AR, NF-kappaB activators and inhibitors
      accelerated and prevented, respectively, their neoplastic transformation induced
      by a chemical carcinogen 3-methylcholanthrene. Bladder tumors were identified in
      56% (mock), 89% (betulinic acid), and 22% (parthenolide) of N-butyl-N-(4
      hydroxybutyl)nitrosamine-treated male C57BL/6 mice at 22 weeks of age. NF-kappaB
      activators and inhibitors also significantly induced and reduced, respectively,
      cell proliferation/migration/invasion of AR-positive bladder cancer lines, but
      not AR-knockdown or AR-negative lines, and their growth in xenograft-bearing
      mice. In both nonneoplastic and neoplastic urothelial cells, NF-kappaB
      activators/inhibitors upregulated/downregulated, respectively, AR expression,
      whereas AR overexpression was associated with increases in the expression levels
      of NF-kappaB/p65 and phospho-NF-kappaB/p65. Thus, NF-kappaB appeared to be
      activated in bladder cancer, which was associated with tumor progression. NF
      kappaB activators/inhibitors were also found to modulate tumorigenesis and tumor
      outgrowth in AR-activated urothelial cells. Accordingly, NF-kappaB inhibition,
      together with AR inactivation, has the potential of being an effective
      chemopreventive and/or therapeutic approach for urothelial carcinoma. Mol Cancer
      Ther; 17(6); 1303-14. (c)2018 AACR.

PMID- 29592879
TI  - Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires
      AMPK Activation.
AB  - We here evaluated the antiesophageal cancer cell activity by the antifungal drug
      itraconazole. Our results show that MUg/mL concentrations of itraconazole
      potently inhibited survival and proliferation of established (TE-1 and Eca-109)
      and primary human esophageal cancer cells. Itraconazole activated AMPK signaling,
      which was required for subsequent esophageal cancer cell death. Pharmacologic
      AMPK inhibition, AMPKalpha1 shRNA, or dominant negative mutation (T172A) almost
      completely abolished itraconazole-induced cytotoxicity against esophageal cancer
      cells. Significantly, itraconazole induced AMPK-dependent autophagic cell death
      (but not apoptosis) in esophageal cancer cells. Furthermore, AMPK activation by
      itraconazole induced multiple receptor tyrosine kinases (RTKs: EGFR, PDGFRalpha,
      and PDGFRbeta), lysosomal translocation, and degradation to inhibit downstream
      Akt activation. In vivo, itraconazole oral gavage potently inhibited Eca-109
      tumor growth in SCID mice. It was yet ineffective against AMPKalpha1 shRNA
      expressing Eca-109 tumors. The in vivo growth of the primary human esophageal
      cancer cells was also significantly inhibited by itraconazole administration.
      AMPK activation, RTK degradation, and Akt inhibition were observed in
      itraconazole-treated tumors. Together, itraconazole inhibits esophageal cancer
      cell growth via activating AMPK signaling. Mol Cancer Ther; 17(6); 1229-39.
      (c)2018 AACR.

PMID- 29592880
TI  - Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP
      Ribose) Polymerase (PARP) Inhibition.
AB  - HER2-targeted therapies, such as trastuzumab, have increased the survival rates
      of HER2+ breast cancer patients. However, despite these therapies, many tumors
      eventually develop resistance to these therapies. Our lab previously reported an
      unexpected sensitivity of HER2+ breast cancer cells to poly (ADP-ribose)
      polymerase inhibitors (PARPi), agents that target homologous recombination (HR)
      deficient tumors, independent of a DNA repair deficiency. In this study, we
      investigated whether HER2+ trastuzumab-resistant (TR) breast cancer cells were
      susceptible to PARPi and the mechanism behind PARPi induced cytotoxicity. We
      demonstrate that the PARPi ABT-888 (veliparib) decreased cell survival in vitro
      and tumor growth in vivo of HER2+ TR breast cancer cells. PARP-1 siRNA confirmed
      that cytotoxicity was due, in part, to PARP-1 inhibition. Furthermore, PARP-1
      silencing had variable effects on the expression of several NF-kappaB-regulated
      genes. In particular, silencing PARP-1 inhibited NF-kappaB activity and reduced
      p65 binding at the IL8 promoter, which resulted in a decrease in IL8 mRNA and
      protein expression. Our results provide insight in the potential mechanism by
      which PARPi induces cytotoxicity in HER2+ breast cancer cells and support the
      testing of PARPi in patients with HER2+ breast cancer resistant to trastuzumab.
      Mol Cancer Ther; 17(5); 921-30. (c)2018 AACR.

PMID- 29592881
TI  - Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of
      Anticancer Drug Through True Active Tumor Targeting.
AB  - Tumor-targeted drug delivery has the potential to improve therapeutic efficacy
      and mitigate non-specific toxicity of anticancer drugs. However, current drug
      delivery approaches rely on inefficient passive accumulation of the drug carrier
      in the tumor. We have developed a unique, truly active tumor-targeting strategy
      that relies on engineering mesenchymal stem cells (MSC) with drug-loaded
      nanoparticles. Our studies using the A549 orthotopic lung tumor model show that
      nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors
      and create cellular drug depots that release the drug payload over several days.
      Despite significantly lower doses of PTX, nano-engineered MSCs resulted in
      significant inhibition of tumor growth and superior survival. Anticancer efficacy
      of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female
      mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at
      doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had
      no effect on white blood cell count, whereas PTX solution and PTX nanoparticle
      treatments caused leukopenia. Biodistribution studies showed that nano-engineered
      MSCs resulted in greater than 9-fold higher AUClung of PTX (1.5 MUg.day/g) than
      PTX solution and nanoparticles (0.2 and 0.1 MUg.day/g tissue, respectively) in
      the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen
      ratios of PTX were several folds higher for nano-engineered MSCs relative to
      those for PTX solution and nanoparticle groups, suggesting that nano-engineered
      MSCs demonstrate significantly less off-target deposition. In summary, our
      results demonstrate that nano-engineered MSCs can serve as an efficient carrier
      for tumor-specific drug delivery and significantly improved anti-cancer efficacy
      of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. (c)2018
      AACR.

PMID- 29592882
TI  - ABT-165, a Dual Variable Domain Immunoglobulin (DVD-Ig) Targeting DLL4 and VEGF,
      Demonstrates Superior Efficacy and Favorable Safety Profiles in Preclinical
      Models.
AB  - Antiangiogenic therapy is a clinically validated modality in cancer treatment. To
      date, all approved antiangiogenic drugs primarily inhibit the VEGF pathway. Delta
      like ligand 4 (DLL4) has been identified as a potential drug target in VEGF
      independent angiogenesis and tumor-initiating cell (TIC) survival. A dual
      specific biologic targeting both VEGF and DLL4 could be an attractive strategy to
      improve the effectiveness of anti-VEGF therapy. ABT-165 was uniquely engineered
      using a proprietary dual-variable domain immunoglobulin (DVD-Ig) technology based
      on its ability to bind and inhibit both DLL4 and VEGF. In vivo, ABT-165 induced
      significant tumor growth inhibition compared with either parental antibody
      treatment alone, due, in part, to the disruption of functional tumor vasculature.
      In combination with chemotherapy agents, ABT-165 also induced greater antitumor
      response and outperformed anti-VEGF treatment. ABT-165 displayed nonlinear
      pharmacokinetic profiles in cynomolgus monkeys, with an apparent terminal half
      life > 5 days at a target saturation dose. In a GLP monkey toxicity study, ABT
      165 was well-tolerated at doses up to 200 mg/kg with non-adverse treatment
      related histopathology findings limited to the liver and thymus. In summary, ABT
      165 represents a novel antiangiogenic strategy that potently inhibits both DLL4
      and VEGF, demonstrating favorable in vivo efficacy, pharmacokinetic, and safety
      profiles in preclinical models. Given these preclinical attributes, ABT-165 has
      progressed to a phase I study. Mol Cancer Ther; 17(5); 1039-50. (c)2018 AACR.

PMID- 29592884
TI  - Mechanistic Modeling of Antibody-Drug Conjugate Internalization at the Cellular
      Level Reveals Inefficient Processing Steps.
AB  - Antibody-drug conjugates (ADC) offer an avenue for specific drug delivery to
      target cells. Here, parameters with important roles in the cellular processing of
      ADCs were quantitatively measured for Ab033, an antibody against EGFR. In EGFR
      overexpressing cancer cell lines, Ab033 internalized at rates of 0.047/min and
      0.15/min for A431 and H441 cells, respectively. Once internalized, Ab033 either
      trafficked to the lysosome or was recycled; up to 45% of internalized Ab033
      returned to the cell surface. Despite such recycling, intracellular accumulation
      of Ab033 continually increased over 24 hours. Ab033 was conjugated to form a dual
      toxin ADC containing both cleavable and non-cleavable linker-drug payloads for
      release rate comparisons. Intracellular concentrations of freed drug from
      cleavable linker were greater than from non-cleavable linker and exceeded 5 * 106
      drug molecules per A431 cell after 24 hours. Compared with intracellular antibody
      accumulation, formation of released drug was delayed, likely due to the time
      needed for endo-lysosomal trafficking and subsequent linker/antibody proteolysis.
      Informed by the quantitative data, a cellular ADC model was constructed and used
      to summarize processing inefficiencies. Modeling simulations were conducted to
      determine parameter sensitivity on intracellular drug concentrations, with rates
      of EGFR internalization and recycling as well as ADC trafficking found to be the
      most sensitive toward final intracellular drug concentrations. Overall, this
      study shows Ab033 ADCs to be a viable strategy for delivery of cytotoxic drugs
      into tumor cells with subsequent modeling efforts able to highlight key
      processing steps to be improved for increased drug delivery. Mol Cancer Ther;
      17(6); 1341-51. (c)2018 AACR.

PMID- 29592883
TI  - Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of
      Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.
AB  - Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters
      tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell
      death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMEC)
      would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing
      glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple
      glioblastoma stem cell (GSC) lines express TfRs, and that their growth is
      inhibited by gallium maltolate (GaM) in vitro After 24 hours of incubation with
      GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose
      dependent decrease in oxygen consumption and a decrease in the activity of the
      iron-dependent M2 subunit of ribonucleotide reductase (RRM2). IHC staining of rat
      and human tumor-bearing brains showed that glioblastoma, but not normal glial
      cells, expressed TfR1 and RRM2, and that glioblastoma expressed greater levels of
      H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma
      xenograft rat model, GaM retarded the growth of brain tumors relative to
      untreated control (P = 0.0159) and reduced tumor mitotic figures (P = 0.045).
      Tumors in GaM-treated animals displayed an upregulation of TfR1 expression
      relative to control animals, thus indicating that gallium produced tumor iron
      deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U
      87 MG and D54 cells in vitro We conclude that GaM enters the brain via TfR1 on
      BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor
      growth. Further development of novel gallium compounds for brain tumor treatment
      is warranted. Mol Cancer Ther; 17(6); 1240-50. (c)2018 AACR.

PMID- 29592885
TI  - Resistance vs resilience to Alzheimer disease: Clarifying terminology for
      preclinical studies.
AB  - Preventing or delaying Alzheimer disease (AD) through lifestyle interventions
      will come from a better understanding of the mechanistic underpinnings of (1) why
      a significant proportion of elderly remain cognitively normal with AD pathologies
      (ADP), i.e., amyloid or tau; and (2) why some elderly individuals do not have
      significant ADP. In the last decades, concepts such as brain reserve, cognitive
      reserve, and more recently brain maintenance have been proposed along with more
      general notions such as (neuro)protection and compensation. It is currently
      unclear how to effectively apply these concepts in the new field of preclinical
      AD specifically separating the 2 distinct mechanisms of coping with pathology vs
      avoiding pathology. We propose a simplistic conceptual framework that builds on
      existing concepts using the nomenclature of resistance in the context of avoiding
      pathology, i.e., remaining cognitively normal without significant ADP, and
      resilience in the context of coping with pathology, i.e., remaining cognitively
      normal despite significant ADP. In the context of preclinical AD studies, we (1)
      define these concepts and provide recommendations (and common scenarios) for
      their use; (2) discuss how to employ this terminology in the context of
      investigating mechanisms and factors; (3) highlight the complementarity and
      clarity they provide to existing concepts; and (4) discuss different study
      designs and methodologies. The application of the proposed framework for framing
      hypotheses, study design, and interpretation of results and mechanisms can
      provide a consistent framework and nomenclature for researchers to reach
      consensus on identifying factors that may prevent ADP or delay the onset of
      cognitive impairment.

PMID- 29592886
TI  - The most affected health domains after ischemic stroke.
AB  - OBJECTIVES: (1) Examine 8 patient-reported domains of health across levels of
      disability compared to the US general population; and (2) identify factors
      associated with domain scores in patients with ischemic stroke. METHODS:
      Observational cohort study of 1,195 patients in a cerebrovascular clinic from
      February 17, 2015, to January 27, 2017, who completed Neuro-QoL (Quality of Life
      in Neurological Disorders) executive function or the following PROMIS (Patient
      Reported Outcomes Measurement Information System) scales as part of routine care:
      physical function, satisfaction with social roles, fatigue, anxiety, depression,
      pain interference, and sleep disturbance. RESULTS: Mean age was 62 (+/-15) years,
      and 81% were white. Median modified Rankin Scale (mRS) score at the clinic visit
      was 1 (interquartile range 0-2). Percentage of patients with scores meaningfully
      worse than the general population ranged from 28% (sleep disturbance) to 63%
      (physical function). Scores were worse in patients with higher mRS levels,
      although correlation between scores and mRS level varied (sleep disturbance r =
      0.16 to physical function r = 0.52). Most affected domains were physical function
      (T score = 58.8), satisfaction with social roles (T score = 55.4), and executive
      function (T score = 53.4). Disability, lower income, and female sex were
      associated with worse scores in multiple domains. Age was associated with worse
      physical function but lower anxiety, depression, and sleep disturbance.
      CONCLUSIONS: Patients with ischemic stroke reported symptoms in multiple domains
      that increase to variable degrees at higher levels of disability. Physical
      function, satisfaction with social roles, and executive function were most
      affected. This information improves our understanding of the well-being of
      patients with ischemic stroke and brings attention to the importance of social
      roles and executive function for stroke survivors.

PMID- 29592887
TI  - Patient-reported outcomes after ischemic stroke as part of routine care.

PMID- 29592888
TI  - Dorsal and ventral horn atrophy is associated with clinical outcome after spinal
      cord injury.
AB  - OBJECTIVE: To investigate whether gray matter pathology above the level of
      injury, alongside white matter changes, also contributes to sensorimotor
      impairments after spinal cord injury. METHODS: A 3T MRI protocol was acquired in
      17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used
      to characterize lesion severity. At the C2-3 level, a high-resolution T2*
      weighted sequence was used to assess cross-sectional areas of gray and white
      matter, including their subcompartments; a diffusion-weighted sequence was used
      to compute voxel-based diffusion indices. Regression models determined
      associations between lesion severity and tissue-specific neurodegeneration and
      associations between the latter with neurophysiologic and clinical outcome.
      RESULTS: Neurodegeneration was evident within the dorsal and ventral horns and
      white matter above the level of injury. Tract-specific neurodegeneration was
      associated with prolonged conduction of appropriate electrophysiologic
      recordings. Dorsal horn atrophy was associated with sensory outcome, while
      ventral horn atrophy was associated with motor outcome. White matter integrity of
      dorsal columns and corticospinal tracts was associated with daily-life
      independence. CONCLUSION: Our results suggest that, next to anterograde and
      retrograde degeneration of white matter tracts, neuronal circuits within the
      spinal cord far above the level of injury undergo transsynaptic
      neurodegeneration, resulting in specific gray matter changes. Such improved
      understanding of tissue-specific cord pathology offers potential biomarkers with
      more efficient targeting and monitoring of neuroregenerative (i.e., white matter)
      and neuroprotective (i.e., gray matter) agents.

PMID- 29592889
TI  - Dissociable influences of APOE epsilon4 and polygenic risk of AD dementia on
      amyloid and cognition.
AB  - OBJECTIVE: To investigate the effects of genetic risk of Alzheimer disease (AD)
      dementia in the context of beta-amyloid (Abeta) accumulation. METHODS: We
      analyzed data from 702 participants (221 clinically normal, 367 with mild
      cognitive impairment, and 114 with AD dementia) with genetic data and florbetapir
      PET available. A subset of 669 participants additionally had longitudinal MRI
      scans to assess hippocampal volume. Polygenic risk scores (PRSs) were estimated
      with summary statistics from previous large-scale genome-wide association studies
      of AD dementia. We examined relationships between APOE epsilon4 status and PRS
      with longitudinal Abeta and cognitive and hippocampal volume measurements.
      RESULTS: APOE epsilon4 was strongly related to baseline Abeta, whereas only weak
      associations between PRS and baseline Abeta were present. APOE epsilon4 was
      additionally related to greater memory decline and hippocampal atrophy in Abeta+
      participants. When APOE epsilon4 was controlled for, PRS was related to cognitive
      decline in Abeta+ participants. Finally, PRSs were associated with hippocampal
      atrophy in Abeta- participants and weakly associated with baseline hippocampal
      volume in Abeta+ participants. CONCLUSIONS: Genetic risk factors of AD dementia
      demonstrate effects related to Abeta, as well as synergistic interactions with
      Abeta. The specific effect of faster cognitive decline in Abeta+ individuals with
      higher genetic risk may explain the large degree of heterogeneity in cognitive
      trajectories among Abeta+ individuals. Consideration of genetic variants in
      conjunction with baseline Abeta may improve enrichment strategies for clinical
      trials targeting Abeta+ individuals most at risk for imminent cognitive decline.

PMID- 29592890
TI  - A novel zebrafish intestinal tumor model reveals a role for cyp7a1-dependent
      tumor-liver crosstalk in causing adverse effects on the host.
AB  - The nature of host organs and genes that underlie tumor-induced physiological
      disruption on the host remains ill-defined. Here, we establish a novel zebrafish
      intestinal tumor model that is suitable for addressing this issue, and find that
      hepatic cyp7a1, the rate-limiting factor for synthesizing bile acids [or, in the
      case of zebrafish, bile alcohol (BA)], is such a host gene. Inducing krasG12D by
      Gal4 specifically expressed in the posterior intestine resulted in the formation
      of an intestinal tumor. The local intestinal tumor caused systemic detrimental
      effects on the host, including liver inflammation, hepatomegaly, growth defects
      and organismal death. Whole-organism-level gene expression analysis and
      metabolite measurements revealed that the intestinal tumor reduced total BA
      levels, possibly via altered expression of hepatic cyp7a1 Genetically
      overexpressing cyp7a1 in the liver restored BA synthesis and ameliorated tumor
      induced liver inflammation, but not other tumor-dependent phenotypes. Thus, we
      found a previously unknown role of cyp7a1 as the host gene that links the
      intestinal tumor, hepatic cholesterol-BA metabolism and liver inflammation in
      tumor-bearing zebrafish larvae. Our model provides an important basis to discover
      host genes responsible for tumor-induced phenotypes and to uncover mechanisms
      underlying how tumors adversely affect host organisms.

PMID- 29592891
TI  - Warfarin alters vitamin K metabolism: a surprising mechanism of VKORC1 uncoupling
      necessitates an additional reductase.
AB  - The anticoagulant warfarin inhibits the vitamin K oxidoreductase (VKORC1), which
      generates vitamin K hydroquinone (KH2) required for the carboxylation and
      consequent activation of vitamin K-dependent (VKD) proteins. VKORC1 produces KH2
      in 2 reactions: reduction of vitamin K epoxide (KO) to quinone (K), and then KH2
      Our dissection of full reduction vs the individual reactions revealed a
      surprising mechanism of warfarin inhibition. Warfarin inhibition of KO to K
      reduction and carboxylation that requires full reduction were compared in wild
      type VKORC1 or mutants (Y139H, Y139F) that cause warfarin resistance.
      Carboxylation was much more strongly inhibited (~400-fold) than KO reduction (two
      to threefold). The K to KH2 reaction was analyzed using low K concentrations
      that result from inhibition of KO to K. Carboxylation that required only K to KH2
      reduction was inhibited much less than observed with the KO substrate that
      requires full VKORC1 reduction (eg, 2.5-fold vs 70-fold, respectively, in cells
      expressing wild-type VKORC1 and factor IX). The results indicate that warfarin
      uncouples the 2 reactions that fully reduce KO. Uncoupling was revealed because a
      second activity, a warfarin-resistant quinone reductase, was not present. In
      contrast, 293 cells expressing factor IX and this reductase activity showed much
      less inhibition of carboxylation. This activity therefore appears to cooperate
      with VKORC1 to accomplish full KO reduction. Cooperation during warfarin therapy
      would have significant consequences, as VKD proteins function in numerous
      physiologies in many tissues, but may be poorly carboxylated and dysfunctional if
      the second activity is not ubiquitously expressed similar to VKORC1.

PMID- 29592892
TI  - Gene dosage effect of CUX1 in a murine model disrupts HSC homeostasis and
      controls the severity and mortality of MDS.
AB  - Monosomy 7 (-7) and del(7q) are high-risk cytogenetic abnormalities common in
      myeloid malignancies. We previously reported that CUX1, a homeodomain-containing
      transcription factor encoded on 7q22, is frequently inactivated in myeloid
      neoplasms, and CUX1 myeloid tumor suppressor activity is conserved from humans to
      Drosophila. CUX1-inactivating mutations are recurrent in clonal hematopoiesis of
      indeterminate potential as well as myeloid malignancies, in which they
      independently carry a poor prognosis. To determine the role for CUX1 in
      hematopoiesis, we generated 2 short hairpin RNA-based mouse models with ~54%
      (Cux1mid) or ~12% (Cux1low) residual CUX1 protein. Cux1mid mice develop
      myelodysplastic syndrome (MDS) with anemia and trilineage dysplasia, whereas
      CUX1low mice developed MDS/myeloproliferative neoplasms and anemia. In diseased
      mice, restoration of CUX1 expression was sufficient to reverse the disease. CUX1
      knockdown bone marrow transplant recipients exhibited a transient hematopoietic
      expansion, followed by a reduction of hematopoietic stem cells (HSCs), and fatal
      bone marrow failure, in a dose-dependent manner. RNA-sequencing after CUX1
      knockdown in human CD34+ cells identified a -7/del(7q) MDS gene signature and
      altered differentiation, proliferative, and phosphatidylinositol 3-kinase (PI3K)
      signaling pathways. In functional assays, CUX1 maintained HSC quiescence and
      repressed proliferation. These homeostatic changes occurred in parallel with
      decreased expression of the PI3K inhibitor, Pik3ip1, and elevated PI3K/AKT
      signaling upon CUX1 knockdown. Our data support a model wherein CUX1 knockdown
      promotes PI3K signaling, drives HSC exit from quiescence and proliferation, and
      results in HSC exhaustion. Our results also demonstrate that reduction of a
      single 7q gene, Cux1, is sufficient to cause MDS in mice.

PMID- 29592893
TI  - Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of
      the gastrointestinal tract.

PMID- 29592894
TI  - Daunorubicin reduces MBNL1 sequestration caused by CUG-repeat expansion and
      rescues cardiac dysfunctions in a Drosophila model of myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disorder caused
      by expression of mutant myotonin-protein kinase (DMPK) transcripts containing
      expanded CUG repeats. Pathogenic DMPK RNA sequesters the muscleblind-like (MBNL)
      proteins, causing alterations in metabolism of various RNAs. Cardiac dysfunction
      represents the second most common cause of death in DM type 1 (DM1) patients.
      However, the contribution of MBNL sequestration in DM1 cardiac dysfunction is
      unclear. We overexpressed Muscleblind (Mbl), the DrosophilaMBNL orthologue, in
      cardiomyocytes of DM1 model flies and observed a rescue of heart dysfunctions,
      which are characteristic of these model flies and resemble cardiac defects
      observed in patients. We also identified a drug - daunorubicin hydrochloride -
      that directly binds to CUG repeats and alleviates Mbl sequestration in Drosophila
      DM1 cardiomyocytes, resulting in mis-splicing rescue and cardiac function
      recovery. These results demonstrate the relevance of Mbl sequestration caused by
      expanded-CUG-repeat RNA in cardiac dysfunctions in DM1, and highlight the
      potential of strategies aimed at inhibiting this protein-RNA interaction to
      recover normal cardiac function.

PMID- 29592896
TI  - Harnessing and Optimizing the Interplay between Immunotherapy and Radiotherapy to
      Improve Survival Outcomes.
AB  - In the past, radiotherapy was primarily used to control local disease, but recent
      technological advances in accurate, high-dose ionizing radiation (IR) delivery
      have not only increased local tumor control but in some cases reduced metastatic
      burden. These "off target" therapeutic effects of IR at nonirradiated tumor
      sites, also known as abscopal effects, are thought to be mediated by tumor
      antigen-primed T cells that travel to metastatic sites and promote tumor
      regression. Similarly, early indications reveal that IR in combination with
      immune checkpoint inhibitors, such as ipilimumab (anti-CTLA-4) and nivolumab
      (anti-PD-1), can provide superior therapeutic responses. These observations
      suggest that local radiotherapy results in altered gene expression, exposure of
      new antigens, or cell death that can interact with immunotherapy. As such,
      radiotherapy enhancement of immune responses offers a promising synergy with the
      potential for substantial clinical benefit. This review focuses on the biology
      that underlies the mechanisms for the interaction between radiation-induced tumor
      cell death and enhanced immunologic response. Mol Cancer Res; 16(8); 1209-14.
      (c)2018 AACR.

PMID- 29592895
TI  - Kinetic Modeling of Virus Growth in Cells.
AB  - When a virus infects a host cell, it hijacks the biosynthetic capacity of the
      cell to produce virus progeny, a process that may take less than an hour or more
      than a week. The overall time required for a virus to reproduce depends
      collectively on the rates of multiple steps in the infection process, including
      initial binding of the virus particle to the surface of the cell, virus
      internalization and release of the viral genome within the cell, decoding of the
      genome to make viral proteins, replication of the genome, assembly of progeny
      virus particles, and release of these particles into the extracellular
      environment. For a large number of virus types, much has been learned about the
      molecular mechanisms and rates of the various steps. However, in only relatively
      few cases during the last 50 years has an attempt been made-using mathematical
      modeling-to account for how the different steps contribute to the overall timing
      and productivity of the infection cycle in a cell. Here we review the initial
      case studies, which include studies of the one-step growth behavior of viruses
      that infect bacteria (Qbeta, T7, and M13), human immunodeficiency virus,
      influenza A virus, poliovirus, vesicular stomatitis virus, baculovirus, hepatitis
      B and C viruses, and herpes simplex virus. Further, we consider how such models
      enable one to explore how cellular resources are utilized and how antiviral
      strategies might be designed to resist escape. Finally, we highlight challenges
      and opportunities at the frontiers of cell-level modeling of virus infections.

PMID- 29592897
TI  - Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk between Ferroptosis
      and Apoptosis.
AB  - Since its discovery in 2012, ferroptosis has been well characterized by the
      accumulation of lipid peroxides due to the failure of glutathione-dependent
      antioxidant defenses. It is known as an iron-dependent form of programmed cell
      death, which is distinct from other forms of cell death such as apoptosis and
      necrosis. Nonetheless, little is known about the ferroptotic agent-induced
      endoplasmic reticulum (ER) stress response and its role in cell death. Recent
      studies reveal that the ferroptotic agent-induced ER stress response plays an
      important role in the cross-talk between ferroptosis and other types of cell
      death. Ferroptotic agents induce the unfolded protein response and subsequently
      ER stress-mediated activation of the PERK-eIF2alpha-ATF4-CHOP pathway. CHOP
      (C/EBP homologous protein) signaling pathway-mediated p53-independent PUMA (p53
      upregulated modulator of apoptosis) expression is involved in the synergistic
      interaction between ferroptosis and apoptosis. This review highlights the recent
      literature on ferroptotic and apoptotic agent interactions through the ER stress
      mediated PERK-eIF2alpha-ATF4-CHOP-PUMA pathway and implicates combined treatment
      to effectively enhance tumoricidal efficacy as a novel therapeutic strategy for
      cancer. Mol Cancer Res; 16(7); 1073-6. (c)2018 AACR.

PMID- 29592898
TI  - Runx2 Suppression by miR-342 and miR-363 Inhibits Multiple Myeloma Progression.
AB  - In multiple myeloma, abnormal plasma cells accumulate and proliferate in the bone
      marrow. Recently, we observed that Runx2, a bone-specific transcription factor,
      is highly expressed in multiple myeloma cells and is a major driver of multiple
      myeloma progression in bone. The primary goal of the present study was to
      identify Runx2-targeting miRNAs that can reduce tumor growth. Expression analysis
      of a panel of miRNAs in multiple myeloma patient specimens, compared with healthy
      control specimens, revealed that metastatic multiple myeloma cells express low
      levels of miR-342 and miR-363 but high levels of Runx2. Reconstituting multiple
      myeloma cells (CAG) with miR-342 and miR-363 reduced the abundance of Runx2 and
      the expression of metastasis-promoting Runx2 target genes RANKL and DKK1, and
      suppressed Runx2 downstream signaling pathways Akt/beta-catenin/survivin, which
      are required for multiple myeloma tumor progression. Intravenous injection of
      multiple myeloma cells (5TGM1), stably overexpressing miR-342 and miR-363 alone
      or together, into syngeneic C57Bl/KaLwRij mice resulted in a significant
      suppression of 5TGM1 cell growth, decreased osteoclasts and increased
      osteoblasts, and increased antitumor immunity in the bone marrow, compared with
      mice injected with 5TGM1 cells expressing a miR-Scramble control. In summary,
      these results demonstrate that enhanced expression of miR-342 and miR-363 in
      multiple myeloma cells inhibits Runx2 expression and multiple myeloma growth,
      decreases osteolysis, and enhances antitumor immunity. Thus, restoring the
      function of Runx2-targeting by miR-342 and miR-363 in multiple myeloma cells may
      afford a therapeutic benefit by preventing multiple myeloma
      progression.Implications: miR-342 and miR-363-mediated downregulation of Runx2
      expression in multiple myeloma cells prevents multiple myeloma progression. Mol
      Cancer Res; 16(7); 1138-48. (c)2018 AACR.

PMID- 29592899
TI  - Synthetic Lethality of PARP Inhibition and Ionizing Radiation is p53-dependent.
AB  - PARP inhibitors (PARPi) are potentially effective therapeutic agents capable of
      inducing synthetic lethality in tumors with deficiencies in homologous
      recombination (HR)-mediated DNA repair such as those carrying BRCA1 mutations.
      However, BRCA mutations are rare, the majority of tumors are proficient in HR
      repair, and thus most tumors are resistant to PARPi. Previously, we observed that
      ionizing radiation (IR) initiates cytoplasmic translocation of BRCA1 leading to
      suppression of HR-mediated DNA repair and induction of synthetic PARPi lethality
      in wild-type BRCA1 and HR-proficient tumor cells. The tumor suppressor p53 was
      identified as a key factor that regulates DNA damage-induced BRCA1 cytoplasmic
      sequestration following IR. However, the role of p53 in IR-induced PARPi
      sensitization remains unclear. This study elucidates the role of p53 in IR
      induced PARPi cytotoxicity in HR-proficient cancer cells and suggests p53 status
      may help define a patient population that might benefit from this treatment
      strategy. Sensitization to PARPi following IR was determined in vitro and in vivo
      utilizing human breast and glioma tumor cells carrying wild-type BRCA1 and p53,
      and in associated cells in which p53 function was modified by knockdown or
      mutation. In breast and glioma cells with proficient HR repair, IR-induced BRCA1
      cytoplasmic sequestration, HR repair inhibition, and subsequent PARPi
      sensitization in vitro and in vivo was dependent upon functional
      p53.Implications: Implications: p53 status determines PARP inhibitor
      sensitization by ionizing radiation in multiple BRCA1 and HR-proficient tumor
      types and may predict which patients are most likely to benefit from combination
      therapy. Mol Cancer Res; 16(7); 1092-102. (c)2018 AACR.

PMID- 29592900
TI  - Genome Sequencing and RNA-Motif Analysis Reveal Novel Damaging Noncoding
      Mutations in Human Tumors.
AB  - A major challenge in cancer research is to determine the biological and clinical
      significance of somatic mutations in noncoding regions. This has been studied in
      terms of recurrence, functional impact, and association to individual regulatory
      sites, but the combinatorial contribution of mutations to common RNA regulatory
      motifs has not been explored. Therefore, we developed a new method, MIRA
      (mutation identification for RNA alterations), to perform an unbiased and
      comprehensive study of significantly mutated regions (SMR) affecting binding
      sites for RNA-binding proteins (RBP) in cancer. Extracting signals related to RNA
      related selection processes and using RNA sequencing (RNA-seq) data from the same
      specimens, we identified alterations in RNA expression and splicing linked to
      mutations on RBP binding sites. We found SRSF10 and MBNL1 motifs in introns,
      HNRPLL motifs at 5' UTRs, as well as 5' and 3' splice-site motifs, among others,
      with specific mutational patterns that disrupt the motif and impact RNA
      processing. MIRA facilitates the integrative analysis of multiple genome sites
      that operate collectively through common RBPs and aids in the interpretation of
      noncoding variants in cancer. MIRA is available at
      https://github.com/comprna/miraImplications: The study of recurrent cancer
      mutations on potential RBP binding sites reveals new alterations in introns,
      untranslated regions, and long noncoding RNAs that impact RNA processing and
      provide a new layer of insight that can aid in the interpretation of noncoding
      variants in cancer genomes. Mol Cancer Res; 16(7); 1112-24. (c)2018 AACR.

PMID- 29592901
TI  - Be brave.

PMID- 29592902
TI  - Countdown for UK Child Survival 2017: mortality progress and targets.
AB  - BACKGROUND: The Countdown for UK Child Survival tracks recent UK child mortality
      trends and makes recommendations for improvement. METHODS: We used data from the
      WHO World Mortality Database to calculate mortality from 1970 to 2014 for 0-19
      year olds in the UK and a comparable group of wealthy countries (the EU15+). We
      used Poisson regression models to assess the significance of apparent
      differences. We extrapolated model coefficients to estimate future disparites
      between the UK and the EU15+ to 2030. We proposed goals and intermediate
      indicators to track UK mortality in keeping with the UN Sustainable Development
      Goals. RESULTS: UK infant mortality continues to track in the worst decile of
      EU15+ mortality with 1-4 year mortality in the worst quartile. Annual reductions
      in total UK mortality have been significantly lower than the EU15+ since 1990 for
      infant, postneonatal and 1-4 year mortality. If current trends persist, by 2030
      UK infant mortality and 1-4 year mortality could be respectively 180% and 145% of
      EU15+ median mortality. UK non-communicable disease (NCD) mortality among 1-4
      years and 15-19 years persists in the worst quartile. UK injury mortality
      continues in the best quartile. A framework of goals and indicators for UK child
      survival and health is presented. DISCUSSION: UK mortality among under 10 years
      of age continues to diverge from the EU15+ median, and UK NCD mortality remains
      persistently poor. We propose a set of goals to improve UK childhood survival by
      2030 and an annual Countdown mechanism to monitor progress towards these targets.

PMID- 29592903
TI  - Adipokine expression and endothelial function in subclinical hypothyroidism rats.

PMID- 29592904
TI  - Matthew McQueen.

PMID- 29592905
TI  - A Man with Recurrent Fractures and Foot Pain.

PMID- 29592906
TI  - Commentary.

PMID- 29592907
TI  - Commentary.

PMID- 29592908
TI  - Dilated Cardiomyopathy and Premature Ovarian Failure Unveiling Propionic
      Aciduria.

PMID- 29592909
TI  - How Low Can Thyroid Tests Go?

PMID- 29592910
TI  - A Young Male with Bilateral Gynecomastia.

PMID- 29592911
TI  - A Test to Ease the Burden of Selecting Patients for Immunotherapy.

PMID- 29592912
TI  - A Patient-Centered Journey.

PMID- 29592915
TI  - Lymphocyte changes and vaccination response in a child exposed to belimumab
      during pregnancy.

PMID- 29592913
TI  - Whole-transcriptome splicing profiling of E7.5 mouse primary germ layers reveals
      frequent alternative promoter usage during mouse early embryogenesis.
AB  - Alternative splicing (AS) and alternative promoter (AP) usage expand the
      repertories of mammalian transcriptome profiles and thus diversify gene
      functions. However, our knowledge about the extent and functions of AS and AP
      usage in mouse early embryogenesis remains elusive. Here, by performing whole
      transcriptome splicing profiling with high-throughput next generation sequencing,
      we report that AS extensively occurs in embryonic day (E) 7.5 mouse primary germ
      layers, and may be involved in multiple developmental processes. In addition,
      numerous RNA splicing factors are differentially expressed and alternatively
      spliced across the three germ layers, implying the potential importance of AS
      machinery in shaping early embryogenesis. Notably, AP usage is remarkably
      frequent at this stage, accounting for more than one quarter (430/1,648) of the
      total significantly different AS events. Genes generating the 430 AP events
      participate in numerous biological processes, and include important regulators
      essential for mouse early embryogenesis, suggesting that AP usage is widely used
      and might be relevant to mouse germ layer specification. Our data underline the
      potential significance of AP usage in mouse gastrulation, providing a rich data
      source and opening another dimension for understanding the regulatory mechanisms
      of mammalian early development.

PMID- 29592916
TI  - Response to: 'Lack of standardization of ANA and implications for drug
      development and precision medicine' by Mahler.

PMID- 29592914
TI  - The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship
      to Hemodialysis Treatment in Patients with ESRD.
AB  - Cardiovascular disease is the leading cause of mortality in patients receiving
      hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week
      pattern; i.e., they occur more commonly during the last day of the long
      interdialytic interval and the first session of the week. The hemodialysis
      process causes acute decreases in cardiac chamber size and pulmonary circulation
      loading and acute diastolic dysfunction, possibly through myocardial stunning and
      other non-myocardial-related mechanisms; systolic function, in contrast, is
      largely unchanged. During interdialytic intervals volume overload, acid-base, and
      electrolyte shifts, as well as arterial and myocardial wall changes, result in
      dilatation of right cardiac chambers and pulmonary circulation overload. Recent
      studies suggest that these alterations are more extended during the long
      interdialytic interval or the first dialysis session of the week and are
      associated with excess volume overload or removal, respectively, thus adding a
      mechanism for the day-of-week pattern of mortality in patients receiving
      hemodialysis. This review summarizes the existing data from echocardiographic
      studies of cardiac morphology and function during the hemodialysis session, as
      well as during the interdialytic intervals.

PMID- 29592917
TI  - Serious infection across biologic-treated patients with rheumatoid arthritis:
      results from the British Society for Rheumatology Biologics Register for
      Rheumatoid Arthritis.
AB  - OBJECTIVES: To compare the incidence of serious infection (SI) across biologic
      drugs used to treat rheumatoid arthritis (RA) using data from the British Society
      for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). METHODS:
      The BSRBR-RA is a prospective observational cohort study. This analysis included
      patients with RA starting a new biologic. The primary outcome was SI defined as
      an infectious event requiring admission to hospital, intravenous antibiotics or
      resulting in death. Event rates were calculated and compared across biologics
      using Cox proportional hazards with adjustment for potential confounders.
      Secondary outcomes were the rate of infection by organ class and 30-day mortality
      following infection. RESULTS: This analysis included 19 282 patients with 46 771
      years of follow-up. The incidence of SI was 5.51 cases per 100 patient years for
      the entire cohort (95% CI 5.29 to 5.71). Compared with etanercept, tocilizumab
      had a higher risk of SI (HR 1.22, 95% CI 1.02 to 1.47) and certolizumab pegol a
      lower risk of SI (HR 0.75, 95% CI 0.58 to 0.97) in the fully adjusted model. The
      30-day mortality following SI was 10.4% (95% CI 9.2% to 11.6%). CONCLUSIONS: The
      rate of SI was lower with certolizumab pegol than etanercept in the primary
      analysis but the result was no longer significant in several sensitivity analyses
      performed suggesting residual confounding may account for the observed
      difference. From these results, it would be wrong to conclude that certolizumab
      pegol has a lower rate of SI than other biologics; however, the risk does not
      appear to be significantly higher as has previously been suggested.

PMID- 29592919
TI  - Funny Old World.

PMID- 29592920
TI  - Helping patients with common mental health problems return to work.

PMID- 29592922
TI  - Doctors and suicide.

PMID- 29592921
TI  - Diabetes outcomes in people with severe mental illness.

PMID- 29592923
TI  - Prescribing for ADHD in primary care.

PMID- 29592924
TI  - Pre-diabetes: opportunity or overdiagnosis?

PMID- 29592918
TI  - Consensus-based recommendations for the management of uveitis associated with
      juvenile idiopathic arthritis: the SHARE initiative.
AB  - BACKGROUND: In 2012, a European initiative called Single Hub and Access point for
      pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate
      diagnostic and management regimens in Europe for children and young adults with
      rheumatic diseases. Juvenile idiopathic arthritis (JIA) is the most common
      rheumatic disease in children and uveitis is possibly its most devastating extra
      articular manifestation. Evidence-based guidelines are sparse and management is
      mostly based on physicians' experience. Consequently, treatment practices differ
      widely, within and between nations. OBJECTIVES: To provide recommendations for
      the diagnosis and treatment of JIA-associated uveitis. METHODS: Recommendations
      were developed by an evidence-informed consensus process using the European
      League Against Rheumatism standard operating procedures. A committee was
      constituted, consisting of nine experienced paediatric rheumatologists and three
      experts in ophthalmology from Europe. Recommendations derived from a validated
      systematic literature review were evaluated by an Expert Committee and
      subsequently discussed at two consensus meetings using nominal group techniques.
      Recommendations were accepted if >80% agreement was reached (including all three
      ophthalmologists). RESULTS: In total, 22 recommendations were accepted (with >80%
      agreement among experts): 3 on diagnosis, 5 on disease activity measurements, 12
      on treatment and 2 on future recommendations. CONCLUSIONS: The SHARE initiative
      aims to identify best practices for treatment of patients suffering from JIA
      associated uveitis. Within this remit, recommendations for the diagnosis and
      treatment of JIA-associated uveitis have been formulated by an evidence-informed
      consensus process to suggest a standard of care for JIA-associated uveitis
      patients throughout Europe.

PMID- 29592925
TI  - Intrusive thoughts of intentional harm to infants.

PMID- 29592926
TI  - PsyScan e-tool to support diagnosis and management of psychological problems in
      general practice.

PMID- 29592927
TI  - Author response.

PMID- 29592928
TI  - Skill-mix change and the general practice workforce challenge.

PMID- 29592929
TI  - WAP plan.

PMID- 29592930
TI  - Author response.

PMID- 29592931
TI  - The world turned upside down: the case for thinking differently about
      undergraduate education.

PMID- 29592932
TI  - Playing the poor in the US.

PMID- 29592933
TI  - Do insulin injections make you fat?

PMID- 29592934
TI  - Forbidden words.

PMID- 29592935
TI  - Bad Medicine: What's up with WhatsApp?

PMID- 29592936
TI  - Yonder: GP trainers, menopause, shared decision making, and coroners' reports.

PMID- 29592937
TI  - Books: The Butchering Art: Joseph Lister's Quest to Transform the Grisly World of
      Victorian Medicine: Transforming the Grisly World of Victorian Medicine.

PMID- 29592938
TI  - Books: Histories: Health, Humanity, Hubris.

PMID- 29592939
TI  - Books: Why We Sleep: The New Science of Sleep and Dreams: Wake Up to Sleep.

PMID- 29592940
TI  - Books: The Intelligent Body: Reversing Chronic Fatigue and Pain from the Inside
      Out: Exploring Software.

PMID- 29592941
TI  - Books: Why We Revolt: A Patient Revolution for Careful and Kind Care: No Care in
      Health Care.

PMID- 29592942
TI  - Are you satisfied?

PMID- 29592943
TI  - Assessing pain in dementia: tools or tacit knowledge (or both)?

PMID- 29592944
TI  - Memory matters: how recall can build resilience.

PMID- 29592945
TI  - An evidence-based first consultation for depression: nine key messages.

PMID- 29592946
TI  - New NICE guidelines for the management of stable angina.

PMID- 29592947
TI  - Biologic agents in inflammatory arthritis.

PMID- 29592948
TI  - TCL1A, a Novel Transcription Factor and a Coregulator of Nuclear Factor kappaB
      p65: Single Nucleotide Polymorphism and Estrogen Dependence.
AB  - T-cell leukemia 1A (TCL1A) single-nucleotide polymorphisms (SNPs) have been
      associated with aromatase inhibitor-induced musculoskeletal adverse events. We
      previously demonstrated that TCL1A is inducible by estradiol (E2) and plays a
      critical role in the regulation of cytokines, chemokines, and Toll-like receptors
      in a TCL1A SNP genotype and estrogen-dependent fashion. Furthermore, TCLIA SNP
      dependent expression phenotypes can be "reversed" by exposure to selective
      estrogen receptor modulators such as 4-hydroxytamoxifen (4OH-TAM). The present
      study was designed to comprehensively characterize the role of TCL1A in
      transcriptional regulation across the genome by performing RNA sequencing (RNA
      seq) and chromatin immunoprecipitation sequencing (ChIP-seq) assays with
      lymphoblastoid cell lines. RNA-seq identified 357 genes that were regulated in a
      TCL1A SNP- and E2-dependent fashion with expression patterns that were 4OH-TAM
      reversible. ChIP-seq for the same cells identified 57 TCL1A binding sites that
      could be regulated by E2 in a SNP-dependent fashion. Even more striking, nuclear
      factor-kappaB (NF-kappaB) p65 bound to those same DNA regions. In summary, TCL1A
      is a novel transcription factor with expression that is regulated in a SNP- and
      E2-dependent fashion-a pattern of expression that can be reversed by 4OH-TAM.
      Integrated RNA-seq and ChIP-seq results suggest that TCL1A also acts as a
      transcriptional coregulator with NF-kappaB p65, an important immune system
      transcription factor.

PMID- 29592949
TI  - In vivo imaging: shining a light on stem cells in the living animal.
AB  - Stem cells are undifferentiated cells that play crucial roles during development,
      growth and regeneration. Traditionally, these cells have been primarily
      characterised by histology, cell sorting, cell culture and ex vivo methods.
      However, as stem cells interact in a complex environment within specific tissue
      niches, there has been increasing interest in examining their in vivo behaviours,
      particularly in response to injury. Advances in imaging technologies and genetic
      tools have converged to enable unprecedented access to the endogenous stem cell
      niche. In this Spotlight article, we highlight how in vivo imaging can probe a
      range of biological processes that relate to stem cell activity, behaviour and
      control.

PMID- 29592950
TI  - The ontogeny, activation and function of the epicardium during heart development
      and regeneration.
AB  - The epicardium plays a key role during cardiac development, homeostasis and
      repair, and has thus emerged as a potential target in the treatment of
      cardiovascular disease. However, therapeutically manipulating the epicardium and
      epicardium-derived cells (EPDCs) requires insights into their developmental
      origin and the mechanisms driving their activation, recruitment and contribution
      to both the embryonic and adult injured heart. In recent years, studies of
      various model systems have provided us with a deeper understanding of the
      microenvironment in which EPDCs reside and emerge into, of the crosstalk between
      the multitude of cardiovascular cell types that influence the epicardium, and of
      the genetic programmes that orchestrate epicardial cell behaviour. Here, we
      review these discoveries and discuss how technological advances could further
      enhance our knowledge of epicardium-based repair mechanisms and ultimately
      influence potential therapeutic outcomes in cardiovascular regenerative medicine.

PMID- 29592951
TI  - BDNF signaling: Harnessing stress to battle mood disorder.

PMID- 29592952
TI  - Global amphibian declines have winners and losers.

PMID- 29592953
TI  - Pharmacological activation of estrogen receptor beta augments innate immunity to
      suppress cancer metastasis.
AB  - Metastases constitute the greatest causes of deaths from cancer. However, no
      effective therapeutic options currently exist for cancer patients with
      metastasis. Estrogen receptor beta (ERbeta), as a member of the nuclear receptor
      superfamily, shows potent tumor-suppressive activities in many cancers. To
      investigate whether modulation of ERbeta could serve as a therapeutic strategy
      for cancer metastasis, we examined whether the selective ERbeta agonist LY500307
      could suppress lung metastasis of triple-negative breast cancer (TNBC) and
      melanoma. Mechanistically, while we observed that LY500307 potently induced cell
      death of cancer cells metastasized to lung in vivo, it does not mediate apoptosis
      of cancer cells in vitro, indicating that the cell death-inducing effects of
      LY500307 might be mediated by the tumor microenvironment. Pathological
      examination combined with flow cytometry assays indicated that LY500307 treatment
      induced significant infiltration of neutrophils in the metastatic niche.
      Functional experiments demonstrated that LY500307-treated cancer cells show
      chemotactic effects for neutrophils and that in vivo neutrophil depletion by Ly6G
      antibody administration could reverse the effects of LY500307-mediated metastasis
      suppression. RNA sequencing analysis showed that LY500307 could induce up
      regulation of IL-1beta in TNBC and melanoma cells, which further triggered
      antitumor neutrophil chemotaxis. However, the therapeutic effects of LY500307
      treatment for suppression of lung metastasis was attenuated in IL1B-/- murine
      models, due to failure to induce antitumor neutrophil infiltration in the
      metastatic niche. Collectively, our study demonstrated that pharmacological
      activation of ERbeta could augment innate immunity to suppress cancer metastatic
      colonization to lung, thus providing alternative therapeutic options for cancer
      patients with metastasis.

PMID- 29592954
TI  - Synergistic activity of cosecreted natural products from amoebae-associated
      bacteria.
AB  - Investigating microbial interactions from an ecological perspective is a
      particularly fruitful approach to unveil both new chemistry and bioactivity.
      Microbial predator-prey interactions in particular rely on natural products as
      signal or defense molecules. In this context, we identified a grazing-resistant
      Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium
      discoideum. Genome analysis of this bacterium revealed the presence of two
      biosynthetic gene clusters that were found adjacent to each other on a contiguous
      stretch of the bacterial genome. Although one cluster codes for the polyketide
      synthase producing the known antibiotic mupirocin, the other cluster encodes a
      nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide
      jessenipeptin. We describe its complete structure elucidation, as well as its
      synergistic activity against methicillin-resistant Staphylococcus aureus, when in
      combination with mupirocin. Both biosynthetic gene clusters are regulated by
      quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL)
      and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules.
      This study highlights the regulation, richness, and complex interplay of
      bacterial natural products that emerge in the context of microbial competition.

PMID- 29592956
TI  - Systematic destruction of healthcare in Eastern Ghouta, Syria.

PMID- 29592955
TI  - Characterizing the human hippocampus in aging and Alzheimer's disease using a
      computational atlas derived from ex vivo MRI and histology.
AB  - Although the hippocampus is one of the most studied structures in the human
      brain, limited quantitative data exist on its 3D organization, anatomical
      variability, and effects of disease on its subregions. Histological studies
      provide restricted reference information due to their 2D nature. In this paper,
      high-resolution (~200 * 200 * 200 MUm3) ex vivo MRI scans of 31 human hippocampal
      specimens are combined using a groupwise diffeomorphic registration approach into
      a 3D probabilistic atlas that captures average anatomy and anatomic variability
      of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens
      was used to label hippocampal subfields in the atlas based on cytoarchitecture.
      Specimens were obtained from autopsies in patients with a clinical diagnosis of
      Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine
      subjects, nine hemispheres), and in subjects without dementia (seven subjects,
      nine hemispheres), and morphometric analysis was performed in atlas space to
      measure effects of age and AD on hippocampal subfields. Disproportional
      involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum
      moleculare was found in AD, with lesser involvement of the dentate gyrus and
      CA2/3 subfields. An association with age was found for the dentate gyrus and, to
      a lesser extent, for CA1. Three-dimensional patterns of variability and disease
      and aging effects discovered via the ex vivo hippocampus atlas provide
      information highly relevant to the active field of in vivo hippocampal subfield
      imaging.

PMID- 29592957
TI  - Intra-Cardiac Release of Extracellular Vesicles Shapes Inflammation Following
      Myocardial Infarction.
AB  - RATIONALE: A rapid and massive influx of inflammatory cells occurs into ischemic
      area after myocardial infarction (MI), resulting in local release of cytokines
      and growth factors. Yet, the mechanisms regulating their production are not fully
      explored. The release of extracellular vesicles (EVs) in the interstitial space
      curbs important biological functions, including inflammation, and influences the
      development of cardiovascular diseases. To date, there is no evidence for in situ
      release of cardiac EVs after MI. OBJECTIVE: The present study tested the
      hypothesis that local EV generation in the infarcted heart coordinates cardiac
      inflammation after MI. METHODS AND RESULTS: Coronary artery ligation in mice
      transiently increases EV levels in the left ventricle when compared with sham
      animals. EVs from infarcted hearts were characterized as large vesicles (252+/-18
      nm) expressing cardiomyocyte and endothelial markers and small EVs (118+/-4 nm)
      harboring exosomal markers, such as CD (cluster of differentiation) 63 and CD9.
      Cardiac large EVs generated after MI, but not small EVs or sham EVs, increased
      the release of IL (interleukin)-6, CCL (chemokine ligand) 2, and CCL7 from
      fluorescence-activated cell-sorted Ly6C+ cardiac monocytes. EVs of similar
      diameter were also isolated from fragments of interventricular septum obtained
      from patients undergoing aortic valve replacement, thus supporting the clinical
      relevance of our findings in mice. CONCLUSIONS: The present study demonstrates
      that acute MI transiently increases the generation of cardiac EVs characterized
      as both exosomes and microvesicles, originating mainly from cardiomyocytes and
      endothelial cells. EVs accumulating in the ischemic myocardium are rapidly taken
      up by infiltrating monocytes and regulate local inflammatory responses.

PMID- 29592959
TI  - Prime minister to bring forward "multiyear" funding boost for the NHS.

PMID- 29592960
TI  - Maintaining reciprocal health rights post-Brexit would benefit UK, says Lords
      report.

PMID- 29592958
TI  - Use of haloperidol versus atypical antipsychotics and risk of in-hospital death
      in patients with acute myocardial infarction: cohort study.
AB  - OBJECTIVE: To compare the risk of in-hospital mortality associated with
      haloperidol compared with atypical antipsychotics in patients admitted to
      hospital with acute myocardial infarction. DESIGN: Cohort study using a
      healthcare database. SETTING: Nationwide sample of patient data from more than
      700 hospitals across the United States. PARTICIPANTS: 6578 medical patients aged
      more than 18 years who initiated oral haloperidol or oral atypical antipsychotics
      (olanzapine, quetiapine, risperidone) during a hospital admission with a primary
      diagnosis of acute myocardial infarction between 2003 and 2014. MAIN OUTCOME
      MEASURE: In-hospital mortality during seven days of follow-up from treatment
      initiation. RESULTS: Among 6578 patients (mean age 75.2 years) treated with an
      oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%)
      initiated atypical antipsychotics. The mean time from admission to start of
      treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar,
      but the mean treatment duration was shorter in patients using haloperidol
      compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1
      propensity score matching was used to adjust for confounding. In intention to
      treat analyses with the matched cohort, the absolute rate of death per 100 person
      days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92
      deaths) during seven days of follow-up from treatment initiation. The survival
      probability was 0.93 in patients using haloperidol and 0.94 in those using
      atypical antipsychotics at day 7, accounting for the loss of follow-up due to
      hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51
      (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The
      association was strongest during the first four days of follow-up and decreased
      over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to
      1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were
      1.90 (1.43 to 2.53) and 1.93 (1.34 to 2.76), respectively. CONCLUSION: The
      results suggest a small increased risk of death within seven days of initiating
      haloperidol compared with initiating an atypical antipsychotic in patients with
      acute myocardial infarction. Although residual confounding cannot be excluded,
      this finding deserves consideration when haloperidol is used for patients
      admitted to hospital with cardiac morbidity.

PMID- 29592961
TI  - Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase Arl8b
      and Determines Cell Death Type in Mycobacterium tuberculosis Infection.
AB  - Mycobacterium tuberculosis is an extremely successful pathogen, and its success
      is widely attributed to its ability to manipulate the intracellular environment
      of macrophages. A central phenomenon of tuberculosis pathology enabling immune
      evasion is the capacity of virulent M. tuberculosis (H37Rv) to induce macrophage
      necrosis, which facilitates the escape of the mycobacteria from the macrophage
      and spread of infection. In contrast, avirulent M. tuberculosis (H37Ra) induces
      macrophage apoptosis, which permits Ag presentation and activation of adaptive
      immunity. Previously, we found that H37Rv induces plasma membrane
      microdisruptions, leading to necrosis in the absence of plasma membrane repair.
      In contrast, H37Ra permits plasma membrane repair, which changes the host cell
      death modality to apoptosis, suggesting that membrane repair is critical for
      sequestering the pathogen in apoptotic vesicles. However, mechanisms of plasma
      membrane repair induced in response to M. tuberculosis infection remain unknown.
      Plasma membrane repair is known to induce a Ca2+-mediated signaling, which
      recruits lysosomes to the area of damaged plasma membrane sites for its
      resealing. In this study, we found that the small GTPase Arl8b is required for
      plasma membrane repair by controlling the exocytosis of lysosomes in cell lines
      and in human primary macrophages. Importantly, we found that the Arl8b secretion
      pathway is crucial to control the type of cell death of the M. tuberculosis
      infected macrophages. Indeed, Arl8b-depleted macrophages infected with avirulent
      H37Ra undergo necrotic instead of apoptotic cell death. These findings suggest
      that membrane repair mediated by Arl8b may be an important mechanism
      distinguishing avirulent from virulent M. tuberculosis-induced necrotic cell
      death.

PMID- 29592962
TI  - Microcrystalline Tyrosine and Aluminum as Adjuvants in Allergen-Specific
      Immunotherapy Protect from IgE-Mediated Reactivity in Mouse Models and Act
      Independently of Inflammasome and TLR Signaling.
AB  - Allergen immunotherapy (AIT) is the only modality that can modify immune
      responses to allergen exposure, but therapeutic coverage is low. One strategy to
      improve AIT safety and efficacy is the use of new or improved adjuvants. This
      study investigates immune responses produced by microcrystalline tyrosine (MCT)
      based vaccines as compared with conventional aluminum hydroxide (alum). Wild
      type, immune-signaling-deficient, and TCR-transgenic mice were treated with
      different Ags (e.g., OVA and cat dander Fel d 1), plus MCT or alum as depot
      adjuvants. Specific Ab responses in serum were measured by ELISA, whereas
      cytokine secretion was measured both in culture supernatants by ELISA or by flow
      cytometry of spleen cells. Upon initiation of AIT in allergic mice, body
      temperature and further clinical signs were used as indicators for anaphylaxis.
      Overall, MCT and alum induced comparable B and T cell responses, which were
      independent of TLR signaling. Alum induced stronger IgE and IL-4 secretion than
      MCT. MCT and alum induced caspase-dependent IL-1beta secretion in human monocytes
      in vitro, but inflammasome activation had no functional effect on inflammatory
      and Ab responses measured in vivo. In sensitized mice, AIT with MCT-adjuvanted
      allergens caused fewer anaphylactic reactions compared with alum-adjuvanted
      allergens. As depot adjuvants, MCT and alum are comparably effective in strength
      and mechanism of Ag-specific IgG induction and induction of T cell responses. The
      biocompatible and biodegradable MCT seems therefore a suitable alternative
      adjuvant to alum-based vaccines and AIT.

PMID- 29592963
TI  - Single Degranulations in NK Cells Can Mediate Target Cell Killing.
AB  - NK cells are cytotoxic lymphocytes important in defense against viral infection
      and cancer. NK cells mediate cytotoxicity predominantly through directed
      secretion of lytic granules, which are specialized lysosome-related organelles,
      containing effector molecules such as perforin and granzymes. Although many
      requirements for lytic granule transport to, and secretion at, the NK cell lytic
      synapse are known, the minimum number of degranulation events required by an NK
      cell to kill its target is unknown. We performed high-resolution four-dimensional
      confocal microscopy of human NK-target cell conjugates to quantify NK cell
      degranulation (using a degranulation indicator, LAMP-1-pHluorin) as well as
      target cell death. Despite containing almost 200 granules, we found that an
      individual NK cell needed only two to four degranulation events, on average, to
      mediate target cell death. Although NK cells released approximately one-tenth of
      their total lytic granule reserve upon a single target, they required just over
      one-hundredth of their total lytic granules to kill a target cell. Importantly,
      the kinetics of NK cell killing correlated to the size of and the amount of
      effector molecules contained within lytic granules, as well as the temporal, but
      not spatial, organization of degranulation events. Thus, our study answers a
      fundamental question as to how many degranulation events it takes for a human NK
      cell to kill its target.

PMID- 29592964
TI  - Local Stimulation of Liver Sinusoidal Endothelial Cells with a NOD1 Agonist
      Activates T Cells and Suppresses Hepatitis B Virus Replication in Mice.
AB  - Functional maturation of liver sinusoidal endothelial cells (LSECs) induced by a
      NOD1 ligand (diaminopimelic acid [DAP]) during viral infection has not been well
      defined. Thus, we investigated the role of DAP-stimulated LSEC maturation during
      hepatitis B virus (HBV) infection and its potential mechanism in a hydrodynamic
      injection (HI) mouse model. Primary LSECs were isolated from wild-type C57BL/6
      mice and stimulated with DAP in vitro and in vivo and assessed for the expression
      of surface markers as well as for their ability to promote T cell responses via
      flow cytometry. The effects of LSEC maturation on HBV replication and expression
      and the role of LSECs in the regulation of other immune cells were also
      investigated. Pretreatment of LSECs with DAP induced T cell activation in vitro.
      HI-administered DAP induced LSEC maturation and subsequently enhanced T cell
      responses, which was accompanied by an increased production of intrahepatic
      cytokines, chemokines, and T cell markers in the liver. The HI of DAP
      significantly reduced the HBsAg and HBV DNA levels in the mice. Importantly, the
      DAP-induced anti-HBV effect was impaired in the LSEC-depleted mice, which
      indicated that LSEC activation and T cell recruitment into the liver were
      essential for the antiviral function mediated by DAP application. Taken together,
      the results showed that the Ag-presenting ability of LSECs was enhanced by DAP
      application, which resulted in enhanced T cell responses and inhibited HBV
      replication in a mouse model.

PMID- 29592965
TI  - Elastin Shapes Small Molecule Distribution in Lymph Node Conduits.
AB  - The spatial and temporal Ag distribution determines the subsequent T cell and B
      cell activation at the distinct anatomical locations in the lymph node (LN). It
      is well known that LN conduits facilitate small Ag distribution in the LN, but
      the mechanism of how Ags travel along LN conduits remains poorly understood. In
      C57BL/6J mice, using FITC as a fluorescent tracer to study lymph distribution in
      the LN, we found that FITC preferentially colocalized with LN capsule-associated
      (LNC) conduits. Images generated using a transmission electron microscope showed
      that LNC conduits are composed of solid collagen fibers and are wrapped with
      fibroblastic cells. Superresolution images revealed that high-intensity FITC is
      typically colocalized with elastin fibers inside the LNC conduits. Whereas
      tetramethylrhodamine isothiocyanate appears to enter LNC conduits as effectively
      as FITC, fluorescently-labeled Alexa-555-conjugated OVA labels significantly
      fewer LNC conduits. Importantly, injection of Alexa-555-conjugated OVA with LPS
      substantially increases OVA distribution along elastin fibers in LNC conduits,
      indicating immune stimulation is required for effective OVA traveling along
      elastin in LN conduits. Finally, elastin fibers preferentially surround lymphatic
      vessels in the skin and likely guide fluid flow to the lymphatic vessels. Our
      studies demonstrate that fluid or small molecules are preferentially colocalized
      with elastin fibers. Although the exact mechanism of how elastin fibers regulate
      Ag trafficking remains to be explored, our results suggest that elastin can be a
      potentially new target to direct Ag distribution in the LN during vaccine design.

PMID- 29592966
TI  - Making Breast Tumors Tamoxifen-Sensitive.
AB  - A new study offers a potential treatment strategy for basal-like breast tumors.
      Researchers found that disrupting platelet-derived growth factor signaling-either
      genetically or with an antibody that blocks one form of the growth factor-can
      cause tumors to change to the luminal subtype, which is susceptible to
      antiestrogen therapies.

PMID- 29592967
TI  - Effect of Achieved Systolic Blood Pressure on Cardiovascular Outcomes in Patients
      With Type 2 Diabetes: A Population-Based Retrospective Cohort Study.
AB  - OBJECTIVE: The objective of this study was to compare the incidence of
      cardiovascular disease (CVD) among patients with type 2 diabetes mellitus (T2DM)
      with treated hypertension who achieved systolic blood pressures (SBPs) of <120,
      <130, and <140 mmHg after an increase in their antihypertensive regimen. RESEARCH
      DESIGN AND METHODS: A retrospective cohort study was conducted on 28,014 primary
      care adult patients with T2DM with no prior diagnosis of CVD and who achieved SBP
      readings <140 mmHg after an increase in the number of antihypertensive
      medications prescribed. Using an extension of propensity score matching, a total
      of 2,079, 10,851, and 15,084 matched patients with achieved SBP measurements of
      <120, <130, and <140 mmHg were identified. The association between achieved SBP
      and incident CVD were evaluated using Cox regressions. Subgroup analyses were
      conducted by stratifying patients' baseline characteristics. RESULTS: Over a
      median follow-up period of 4.8 years, the incidence of CVD in patients with
      achieved SBP measures of <120, <130, and <140 mmHg were 318 (15.3%; incidence
      rate [IR] 34.3/1,000 person-years [PY]), 992 (9.1%; IR 20.4/1,000 PY), and 1,635
      (10.8%; IR 21.4/1,000 PY). Achieved SBP <120 mmHg was associated with a higher
      risk of CVD compared with achieved SBP <130 mmHg (hazard ratio [HR] 1.75 [95% CI
      1.53, 2.00]) and achieved SBP <140 mmHg (HR 1.67 [95% CI 1.46, 1.90]). There was
      a significant reduction in CVD risk in patients <65 years (HR 0.81 [95% CI 0.69,
      0.96]) but no difference for other patients, including patients >=65 years, who
      achieved SBP <130 mmHg when compared with the group that achieved SBP <140 mmHg.
      CONCLUSIONS: Our findings support a SBP treatment target of 140 mmHg and suspect
      no risk reduction attenuation on CVD for lower SBP targets (<120 or <130 mmHg)
      for most patients with uncomplicated T2DM. A randomized control trial is still
      needed to confirm these findings.

PMID- 29592968
TI  - NHS should work with WhatsApp to create a new service.

PMID- 29592969
TI  - Association of Birthplace and Coronary Heart Disease and Stroke Among US Adults:
      National Health Interview Survey, 2006 to 2014.
AB  - BACKGROUND: The proportion of foreign-born US adults has almost tripled since
      1970. However, less is known about the cardiovascular morbidity by birthplace
      among adults residing in the United States. This study's objective was to compare
      the prevalence of coronary heart disease (CHD) and stroke among US adults by
      birthplace. METHODS AND RESULTS: We used data from the 2006 to 2014 National
      Health Interview Survey. Birthplace was categorized as United States or foreign
      born. Foreign born was then grouped into 6 birthplace regions. We defined CHD and
      stroke as ever being told by a physician that she or he had CHD or stroke. We
      adjusted for select demographic and health characteristics in the analysis. Of US
      adults, 16% were classified as foreign born. Age-standardized prevalence of both
      CHD and stroke were higher among US- than foreign-born adults (CHD: 8.2% versus
      5.5% for men and 4.8% versus 4.1% for women; stroke: 2.7% versus 2.1% for men and
      2.7% versus 1.9% for women; all P<0.05). Comparing individual regions with those
      of US- born adults, CHD prevalence was lower among foreign-born adults from Asia
      and Mexico, Central America, or the Caribbean. For stroke, although men from
      South America or Africa had the lowest prevalence, women from Europe had the
      lowest prevalence. Years of living in the United States was not related to risk
      of CHD or stroke after adjustment with demographic and health characteristics.
      CONCLUSIONS: Overall, foreign-born adults residing in the United States had a
      lower prevalence of CHD and stroke than US-born adults. However, considerable
      heterogeneity of CHD and stroke risk was found by region of birth.

PMID- 29592970
TI  - Spatio-temporal MAPK dynamics mediate cell behavior coordination during fungal
      somatic cell fusion.
AB  - Mitogen-activated protein kinases (MAPKs) are conserved regulators of
      proliferation, differentiation and adaptation in eukaryotic cells. Their activity
      often involves changes in their subcellular localization, indicating an important
      role for these spatio-temporal dynamics in signal transmission. A striking model
      illustrating these dynamics is somatic cell fusion in Neurospora crassa
      Germinating spores of this fungus rapidly alternate between signal sending and
      receiving, thereby establishing a cell-cell dialog, which involves the
      alternating membrane recruitment of the MAPK MAK-2 in both fusion partners. Here,
      we show that the dynamic translocation of MAK-2 is essential for coordinating the
      behavior of the fusion partners before physical contact. The activation and
      function of the kinase strongly correlate with its subcellular localization,
      indicating a crucial contribution of the MAPK dynamics in establishing regulatory
      feedback loops, which establish the oscillatory signaling mode. In addition, we
      provide evidence that MAK-2 not only contributes to cell-cell communication, but
      also mediates cell-cell fusion. The MAK-2 dynamics significantly differ between
      these two processes, suggesting a role for the MAPK in switching of the cellular
      program between communication and fusion.

PMID- 29592972
TI  - Drug-induced movement disorder and confusion associated with duloxetine.
AB  - A 60-year-old woman with major depressive disorder, developed high blood
      pressure, confusion and dyskinesias of face, neck and jaw, following an increase
      in her dose of duloxetine. Routine blood tests including toxic, infective and
      metabolic workup were unremarkable. Cerebrospinal fluid analysis and
      electroencephalogram were also normal. MRI brain showed bilaterally symmetrical
      diffusion-restricted areas in deep cerebral white matter. Duloxetine was held on
      suspicion of drug adverse effect. She had complete resolution of symptoms within
      48 hours and resolution of MRI brain changes over 6 weeks. Serotonin
      norepinephrine reuptake inhibitors such as duloxetine may have the potential to
      cause drug-induced movement disorders, confusion and high blood pressure and
      should be used cautiously especially in elderly.

PMID- 29592971
TI  - The Joubert syndrome protein ARL13B binds tubulin to maintain uniform
      distribution of proteins along the ciliary membrane.
AB  - Cilia-mediated signal transduction involves precise targeting and localization of
      selected molecules along the ciliary membrane. However, the molecular mechanism
      underlying these events is unclear. The Joubert syndrome protein ARL13B is a
      membrane-associated G-protein that localizes along the cilium and functions in
      protein transport and signaling. We identify tubulin as a direct interactor of
      ARL13B and demonstrate that the association occurs via the G-domain and
      independently from the GTPase activity of ARL13B. The G-domain is necessary for
      the interaction of ARL13B with the axoneme both in vitro and in vivo We further
      show that exogenously expressed mutants lacking the tubulin-binding G-domain
      (ARL13B-DeltaGD) or whose GTPase domain is inactivated (ARL13B-T35N) retain
      ciliary localization, but fail to rescue ciliogenesis defects of null Arl13bhnn
      mouse embryonic fibroblasts (MEFs). However, while ARL13B-DeltaGD and the
      membrane proteins Smoothened (SMO) and Somatostatin receptor-3 (SSTR3) distribute
      unevenly along the cilium of Arl13bhnn MEFs, ARL13B-T35N distributes evenly along
      the cilium and enables the uniform distribution of SMO and SSTR3. Thus, we
      propose a so far unknown function of ARL13B in anchoring ciliary membrane
      proteins to the axoneme through the direct interaction of its G-domain with
      tubulin.

PMID- 29592973
TI  - Cortical laminar necrosis in a case of migrainous cerebral infarction.
AB  - We report a 27-year-old woman, a known case of classical migraine headache, on
      oral contraceptive pills. She had a severe episode of migraine with visual aura
      attack, which continued late into the night. The next early morning, her headache
      persisted and she developed abrupt onset of dysarthria, right hemiparaesthesias.
      She attributed symptoms to her long-standing headache problem, and hence did not
      seek medical help for the next two weeks. The symptoms persisted despite her
      headache subsiding over the next 24 hours. She worsened 2 weeks later during
      another such episode of headache. This time, she developed right hemiparesis. The
      patient was admitted with provisional diagnosis of stroke. MRI of the brain
      showed left temporoparietal lesion and was radiologically compatible with
      cortical laminar necrosis.Extensive work-up was done to rule out other causes of
      young stroke. The patient improved with antiplatelets, antimigraine prophylaxis
      and stroke rehabilitation therapy.

PMID- 29592974
TI  - Sodium nitroprusside, a lifesaving treatment for neonatal hypertension: an Irish
      experience.
AB  - We present a 30+2-weeks-old (30 weeks and 2 days) male, twin 1, born by emergency
      caesarean section due to twin-twin transfusion syndrome (absent end-diastolic
      flow and cardiac anomaly in twin 2) presenting with hypertensive crisis on day 3.
      He was already on milrinone and propranolol. His echocardiogram showed poor left
      ventricular contractility and after cardiology consultation received sodium
      nitroprusside, which eventually saved his life by decreasing his blood pressure
      and improving cardiac function. As sodium nitroprusside is very rarely used for
      hypertensive crisis in neonates, we would like to share our experiences on
      dosage, challenges in administration due to its fast onset of action, criteria
      for monitoring for complications and finally weaning. Baby developed severe
      bilateral periventricular leukomalacia as a potential complication of
      hypertensive crisis, preceded by bilateral periventricular flare secondary to
      twin-twin transfusion.

PMID- 29592975
TI  - Fulminant hepatic failure in the setting of progressive ANCA-associated
      vasculitis associated with a rare alpha-1 antitrypsin phenotype, 'PiEE'.
AB  - Abnormalities in alpha-1 antitrypsin (AAT) proteins are risk factors for human
      disease. While the most common is AAT deficiency, a genetic disorder associated
      with chronic obstructive pulmonary disease, additional disorders associated with
      AAT abnormalities are increasingly recognised. We describe a middle-aged woman
      who presented with fulminant hepatic and multiorgan failure. Evaluation revealed
      the patient to have a rare AAT phenotype PiEE. Her clinical presentation was
      consistent with antineutrophilic cytoplasmic antibody-associated vasculitis, and
      her history suggested features of panniculitis. This is the first description of
      this rare homozygous AAT phenotype and possible disease associations with the 'E'
      protein. Given that abnormal AAT are under-recognised, and that new mutations and
      phenotypes continue to be identified, we will need to expand on our knowledge
      base and report clinical manifestations associated with these abnormal
      phenotypes.

PMID- 29592976
TI  - Localisation of ectopic mediastinal parathyroid adenoma by 18F-fluorocholine
      PET/CT.
AB  - We report the case of two patients with newly diagnosed primary
      hyperparathyroidism: a 40-year-old woman during pregnancy and a 60-year-old man
      with initial hypercalcaemic crisis. In the first case, a bilateral neck
      exploration with parathyroidectomy during the second trimester of pregnancy was
      unsuccessful and the patient remained hypercalcaemic. Postpartum imaging
      assessment with technetium (99mTc)-sestamibi scintigraphy could not supply
      conclusive diagnostic results. The use of 18F-fluorocholine (FCH) positron
      emission tomography (PET)/CT provided the accurate localisation of an ectopic
      parathyroid adenoma in the anterior mediastinum which was successfully resected
      by a thoracoscopic approach. In the second case, 99mTc-sestamibi scintigraphy was
      inconclusive as well and FCH-PET/CT localised an ectopic parathyroid adenoma in
      the mediastinum and thus bilateral neck exploration could be spared. Both
      patients had surgical cure of their disease.

PMID- 29592977
TI  - Artery of Percheron: an unusual stroke presentation.
AB  - An 86-year-old woman was admitted with multiple episodes of transient loss of
      consciousness. She was initially treated for seizures, and stroke was not
      considered likely. MRI on the same day of admission showed acute bilateral medial
      thalamic infarcts in keeping with the Artery of Percheron (AOP) territory
      infarcts. Investigation for polycythaemia and thrombocytosis showed JAK2 positive
      myeloproliferative neoplasm.A diagnosis of AOP infarction is often missed or
      delayed because it is rare and presents with variable neurological symptoms.
      Initial imaging in the form of CT is often negative, and some report that initial
      MRI findings may also be normal.An awareness of a wide range of differential
      diagnoses alongside a multi-modality imaging approach is required to reach a
      diagnosis.Although there are several other case reports of AOP infarction in the
      literature, this is the first to present with transient symptoms initially
      mistaken for seizure activity.

PMID- 29592978
TI  - Hypoglossal nerve stimulation for obstructive sleep apnoea in a patient with
      previous tongue laceration.
AB  - Upper airway stimulation of the tongue using an implantable neurostimulator has
      recently been approved for select patients with moderate to severe obstructive
      sleep apnoea (OSA) and intolerance to continuous positive airway pressure
      therapy. Effective implantation depends on the integrity of the hypoglossal nerve
      as well as the tongue musculature, notably the genioglossus. Prior trauma to
      either of these structures may be viewed as a relative contraindication to
      implantation. We describe a case of successful right hypoglossal nerve
      implantation in a patient with a history of left cardiac pacemaker placement and
      severe left penetrating tongue trauma with decreased mobility from contracture
      and deviation mimicking a hypoglossal nerve palsy. Preoperative and postoperative
      apnoea-hypopnoea index values were 52/hour and 5/hour, respectively. Prior soft
      tissue trauma to the tongue may not necessarily preclude surgical candidacy for
      upper airway stimulation in patients with OSA.

PMID- 29592979
TI  - Spondylodiscitis in a 54-year-old female scuba diver.
AB  - A 54-year-old woman presented to a Sports Physician with a 4-year history of
      haemochromatosis, and she had a medical history that included a congenital
      spondylolisthesis resulting in a fusion of L4-S1 at age 16 years, episodic
      mechanical low back pain and an absence of other significant musculoskeletal
      symptoms. On presentation, she reported 18 months of severe low back pain that
      started after a scuba diving trip. After the onset of this low back pain, she
      developed gastrointestinal symptoms from Salmonella The gastrointestinal symptoms
      improved with a course of antibiotics, but the back pain persisted in spite of
      analgesics, non-steroidal anti-inflammatories and several attempts at different
      conservative management. CT imaging ordered by the Sports Physician demonstrated
      an erosive spondylodiscitis of L2/3 that was not present on initial
      investigations. However, even in the presence of significant bony changes, the
      patient was successfully treated with targeted conservative therapy.

PMID- 29592980
TI  - Metastatic pheochromocytoma in MEN 2A: A rare association.
AB  - A 45-year-old woman was diagnosed as having multiple endocrine neoplasia type 2A
      in 2014. She had bilateral pheochromocytoma, medullary thyroid carcinoma and
      biopsy-proven cutaneous lichen amyloidosis in the interscapular area. She
      underwent bilateral adrenalectomy; following which, she achieved clinical and
      biochemical remission. She was planned for total thyroidectomy at a later date;
      however, she was lost to follow-up. She presented to us again in December 2016
      with abdominal pain. Examination revealed hypertension with postural drop.
      Positron emission tomography scan showed Ga68 and fluorodeoxyglucose (FDG)-avid
      suprarenal, hepatic, peritoneal and mesenteric masses with abdominal lymph nodes.
      Twenty-four-hour urinary metanephrines/normetanephrines were elevated. Serum
      calcitonin was as high as it was 2-1/2 years ago. Ultrasonography-guided fine
      needle aspiration cytology (FNAC) from the liver mass revealed neuroendocrine
      cells that did not stain for calcitonin. Hence, a diagnosis of metastatic
      pheochromocytoma was made. She underwent total thyroidectomy and was started on
      cyclophosphamide, vincristine, dacarbazine-based chemotherapy regimen.

PMID- 29592981
TI  - Burn aggravated infected wart in a patient with type 2 diabetes: a medical
      challenge.
AB  - An infectious wart of foot in a patient with diabetics is a medical challenge,
      and it gets worse when aggravated with burns. We present a case of a 67-year-old
      Pakistani man, diabetic for 20 years presented at our healthcare centre. While
      awaiting his culture sensitivity report, he was prescribed an empiric antibiotic
      therapy. Patient then travelled to Saudi Arabia for pilgrimage 3 days later with
      growth of Staphylococcus aureus and Proteus species in culture and sensitivity
      report; during his travel, he walked barefoot and the infected wart aggravated
      with severe burn. Patient continued empiric treatment for 14 days. On his
      arrival, infected wart worsened with dead burnt skin, heavy purulent discharge on
      plantar region. X-rays revealed marked arthritic changes. Cefepime 500 mg three
      times a day intravenously was initiated following wound debridement. Patient was
      switched to moxifloxacin 400 mg once daily postoperatively for 7 days until
      completely healed.

PMID- 29592982
TI  - Pulmonary alveolar proteinosis following cryptococcal meningitis: a possible
      cause?
AB  - Autoimmune pulmonary alveolar proteinosis (PAP) is a rare interstitial lung
      disease characterised by the presence of granulocyte macrophage colony
      stimulating factor (GM-CSF) autoantibodies. A man with no history of infection
      developed cryptococcal meningitis and a right parahilar cryptococcal mass.
      Antifungal treatment led to infection control, although there was presence of
      neurological sequelae. After 3 years, thoracic CT revealed bilateral ground glass
      opacities and a crazy paving pattern. Transparietal needle biopsy showed
      proteinaceous alveolar deposits, confirming the diagnosis of PAP. A high titre of
      serum anti-GM-CSF autoantibodies was found. No specific treatment was started,
      and radiological lesions decreased progressively. Cryptococcal infection may
      occur in PAP and in patients with anti-GM-CSF antibodies without PAP. These
      antibodies dysregulate phagocytosis in monocytes and macrophages, possibly
      leading to opportunistic infections in previously healthy subjects.

PMID- 29592983
TI  - Rare cause of fever of unknown origin: gastrointestinal stromal tumour.
AB  - A 44-year-old man presented with fever (low to high grade) for 2-month duration
      despite treatment with oral antibiotics and antipyretics. Further, enquiry did
      not yield any potentially explanatory clues to a diagnosis. Physical examination
      revealed only left axillary lymphadenopathy, but was otherwise unremarkable. A
      number of diagnosis included tuberculosis, malignancy, lymphoma, connective
      disease disorder and infective endocarditis. Further evaluation revealed severe
      anaemia due to iron deficiency which was supported with blood transfusion and
      oral iron supplementation. Septic work-up including blood cultures and urine
      culture sterile and procalcitonin, but all these proved negative. Transthoracic
      echocardiography followed by transoesophageal echocardiography did not reveal any
      vegetations suggestive of infective endocarditis. Contrast-enhanced CT of chest
      and abdomen showed a polypoidal mass in the caecum. Lymph node biopsy from left
      axillary lymph node showed changes consistent with reactive hyperplasia. A bone
      marrow biopsy was inconclusive. Mantoux test was negative. A colonoscopy revealed
      a polypoidal growth arising from caecum with dull-looking mucosa. Biopsy of the
      mass suggested a leiomyoma. Positron emission tomography CT showed
      fluorodeoxyglucose (FDG)-avid caecal mass with FDG-avid mesenteric lymph nodes
      (figure 1). Inspite of extensive work-up, we could not find a source of the fever
      except for caecal mass. Thus, in the absence of other explanatory findings, a
      decision for resection of the mass was taken. A laparoscopic right hemicolectomy
      done with primary anastomosis. Histology confirmed a gastrointestinal stromal
      tumour (figure 2, which was smooth muscle actin positive (figure 3), S-100
      positive, vimentin positive, but c-KIT negative (figure 4), CD34 positive and
      desmin negative. Additional immunohistochemistry and gene mutational analysis
      could not be done due to resource limitations. The postoperative course was good,
      and the patient was followed for 9 months after surgery with good clinical
      recovery and no further fever. This case illustrates the need for high index of
      suspicion to diagnose malignancy as cause of fever.

PMID- 29592984
TI  - A rare cause of postpartum headache.
AB  - Postpartum women can develop headache, and their assessment requires a thorough
      and multidisciplinary approach. If the headache is unresponsive to treatment and
      accompanied by neurological deficit, neuroimaging needs to be undertaken to rule
      out other life-threatening causes. 1 We present a case of 35-year-old woman with
      pre-eclampsia and diet-controlled gestational diabetes mellitus, who had normal
      vaginal delivery at 40 weeks. She had an epidural analgesia for pain relief
      during labour, but had inadvertent dural puncture during the procedure and
      developed headache 24 hours after delivery. The headache was managed
      conservatively and she was discharged home, but was readmitted 8 days later with
      worsening headache. The headache was postural on admission but became continuous,
      developed neurological symptoms in the form of ataxic hemiparesis and
      convulsions. After neuroimaging, she was found to have cerebral venous sinus
      thrombosis. She was commenced on anticoagulants and anticonvulsants and made a
      complete recovery.

PMID- 29592986
TI  - Pleomorphic adenoma of nasal septum: a rare case.
AB  - The most common benign tumour of the major salivary glands is the pleomorphic
      adenoma. They are seen rarely in the minor salivary glands, usually in hard
      palate, soft palate and nasopharynx. Pleomorphic adenomas in nasal cavity are
      unusual and may be misdiagnosed because they have predominant myoepithelial
      cellularity and fewer myxoid stromata compared with those elsewhere. We present a
      case of 38-year-old male with a 2-year history of left nasal obstruction and
      epistaxis since 6 months. Diagnostic nasal endoscopic examination showed a soft
      lobulated mass in left nasal cavity attached to anterior part of the septum.
      Radiological examination demonstrated soft tissue mass filling left nasal cavity
      with an eroded septum. The biopsy from the mass was suggestive of pleomorphic
      adenoma and was resected endoscopically. Histopathological examination was
      consistent with pleomorphic adenoma. These are rare tumours of the nasal cavity
      and can be managed effectively with the endoscopic approach.

PMID- 29592985
TI  - Caffeine to prevent respiratory failure and improve outcome in infant pertussis.
AB  - Pertussis remains a dangerous disease for children around the world, especially
      for infants less than 6 months old. In this age group, high mortality and
      morbidity have been linked to the effects of the pertussis toxin, including
      lymphocytosis, pulmonary hyperviscosity and pulmonary hypertension. This paper
      reports on an infant with pertussis who received therapeutic caffeine. Caffeine
      might improve outcomes in pertussis by preventing apnoea, improving respiratory
      drive and decreasing pulmonary complications.

PMID- 29592987
TI  - Seizure-induced unilateral posterior dislocation of the shoulder: a diagnosis not
      to be missed.
AB  - A man in his mid-50s with a history of bladder carcinoma presented to the
      Emergency Department (ED) following a witnessed tonic-clonic seizure. Computed
      Tomography (CT) scanning of his brain revealed an indeterminate mass lesion in
      the left parietal region. The patient described bilateral shoulder pain prompting
      plain film radiographs with axial views, but no obvious abnormality was
      identified by the ED staff. Staging CT scanning did not reveal any evidence of
      underlying malignancy but revealed dislocation of the left humeral head with a
      large reverse Hill-Sachs lesion and posteriorly displaced reverse Bankart lesion.
      Manipulation under anaesthesia and closed reduction of the left shoulder was
      undertaken successfully. This case report reminds the clinician to maintain a
      high index of suspicion for posterior dislocation of the shoulder following
      seizures and to perform appropriate imaging promptly.

PMID- 29592988
TI  - Paediatric forearm fracture with a twist: a proximal radioulnar translocation
      combined with radial head fracture.
AB  - A 10-year-old girl presented to the emergency department with proximal radioulnar
      translocation and radial head fracture, after fall onto an outstretched hand.
      Open reduction was used to reduce and stabilise the elbow joint after which the
      radial head was fixated by Kirschner wires. Three months after surgery, full
      range of motion was regained and union of the radial head was achieved. Proximal
      radioulnar translocation is a rare injury which is often missed on initial
      radiographs. Persistent restriction of forearm rotation with seemingly normal
      elbow configuration must trigger to take a closer look at the relationship
      between the ulna, radius and distal humerus. We show that early diagnosis and
      treatment of a proximal radioulnar translocation associated with a radial head
      fracture results in an excellent functional outcome.

PMID- 29592989
TI  - Severe acute haemolytic anaemia associated with severe methaemoglobinaemia in a
      G6PD-deficient man.
AB  - Methaemoglobin is a form of haemoglobin in which the ferrous (Fe2+) ion contained
      in the iron-porphyrin complex of haem is oxidised to its ferric (Fe3+) state.
      Methaemoglobinaemia, the presence of methaemoglobin in the blood, is most
      commonly treated with methylene blue. However, methylene blue cannot be used in
      patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it is
      ineffective in such patients and it can worsen G6PD deficiency haemolysis. We
      report the case of a 30-year-old man who presented with clinical features of G6PD
      deficiency-associated haemolysis and was found to have severe methaemoglobinaemia
      (35%). He was administered blood transfusions and intravenous ascorbic acid. His
      methaemoglobinaemia resolved within 24 hours. This case demonstrates the
      successful management of a patient with severe methaemoglobinaemia in the setting
      of G6PD deficiency haemolysis. Emergency physicians should be aware of the
      possible co-occurrence of severe methaemoglobinaemia in a patient with G6PD
      deficiency haemolysis.

PMID- 29592990
TI  - Management of a rhegmatogenous retinal detachment in a low-resource setting:
      treatment options when there is no vitreoretinal surgeon.
AB  - We discuss the case of a 49-year-old soldier with a macula-on rhegmatogenous
      retinal detachment in Sierra Leone. The case highlights the challenge of
      accessing visually preserving ophthalmic specialist care in sub-Saharan Africa
      (SSA) for vitreoretinal (VR) disease. It highlights a shortage of VR surgeons in
      SSA, limited examination facilities, the larger issue of accessing specialist
      care urgently and the costs associated with accessing surgery out-of-country. It
      also identifies a shortage in epidemiological data on the issue which limits the
      assessment of the scale of the problem.

PMID- 29592991
TI  - De Garengeot's hernia: a rare presentation of the wandering appendix.
AB  - A hernia is defined as a protrusion of an organ or its fascia through a sac of
      its containing cavity. The presentation of an inflamed appendix inside an
      incarcerated femoral hernia is termed de Garengeot's hernia. Almost exclusively
      seen in the female patient, this type of hernia like all others can undergo
      strangulation leading to complications including appendicitis with or without
      perforation. Management as described in literature usually comprises open or
      laparoscopic approach, followed by appendectomy and repair of the femoral hernia
      with or without mesh. We describe a case of a female patient who presented with
      an irreducible groin swelling, found to have a femoral hernia containing the
      inflamed appendix intraoperatively and how it was managed surgically through a
      laparoscopic approach with a small mesh and closure of defect. Literature review
      on this rare form of hernia is discussed thereafter.

PMID- 29592992
TI  - Aural foreign body in situ for 9 years mimicking impacted wax.

PMID- 29592993
TI  - Systemic inflammatory response in a liver transplant recipient: a potential side
      effect of mycophenolate mofetil.
AB  - Mycophenolate mofetil is a commonly used immunosuppressive medication in the
      postliver transplant setting where gastrointestinal side effects tend to
      predominate. However, in more recent times, emerging and rare side effects are
      being reported in the literature. We present a case of a patient who had a
      significant inflammatory response and associated marked weight loss with the
      uptitration in dose of mycophenolate mofetil. Extensive investigations were
      performed to exclude other infective, inflammatory or malignant aetiologies for
      these symptoms, however no other cause was identified. The patient had the
      medication ceased and subsequently had a dramatic improvement in his inflammatory
      markers and regained the weight lost while on the medication.

PMID- 29592994
TI  - Rare case of cystic artery pseudoaneurysm.
AB  - A patient with a cystic artery pseudoaneurysm (CAP) presented to the emergency
      department with upper abdominal and back pain. The patient also had clinical
      signs of sepsis. CT revealed gallstones with acute suppurative cholecystitis with
      a gallbladder perforation. In addition, a CAP was also suspected and subsequently
      diagnosed on CT angiography. The pseudoaneurysm was treated with embolisation and
      a cholecystostomy was performed for the gallbladder perforation. Following her
      acute admission, the patient underwent an elective cholecystectomy and made a
      good recovery post surgery.

PMID- 29592995
TI  - A rare case of pyogenic pericarditis secondary to Streptococcus constellatus.
AB  - We report an extremely rare case of purulent pericarditis caused by the normally
      commensal oral flora, Streptococcus constellatus, a viridans Streptococcal
      species and member of the S. anginosus group (previously also known by the
      eponymous 'S. milleri', for American Willoughby Dayton Miller). This case is a
      previously healthy 71-year-old immunocompetent woman from Arizona who presented
      with a 5-day history of progressive shortness of breath and chest tightness, and
      subjective fever and chills, but without history of nausea, vomiting, night
      sweats, recent travel, autoimmune disease or sick contacts. Early recognition and
      intervention of purulent pericarditis allow patients like the one outlined in
      this case to achieve full recovery.

PMID- 29592996
TI  - Trauma-induced adiposis dolorosa (Dercum's disease).
AB  - We present a case of a 39-year-old man who presented with chronic bilateral upper
      extremity pain associated with innumerable angiomyolipomas that developed 5 years
      after a motor vehicle accident involving his upper extremities. Our case notes
      the rare nature of painful adipose tissue deposits and the diagnostic challenges.

PMID- 29592997
TI  - Cornual ectopic pregnancy: laparoscopic management step by step.
AB  - Cornual (interstitial) ectopic pregnancy is an uncommon type of ectopic pregnancy
      which is located in the interstitial part of the fallopian tube. It accounts for
      2%-4% of all ectopic pregnancies. Cornual pregnancies often pose a diagnostic and
      therapeutic challenge with a significant high morbidity and mortality as a result
      of massive intraperitoneal bleeding. A case of unruptured cornual ectopic
      pregnancy in a patient with abnormal uterine bleeding is reported which was
      successfully managed laparoscopically.

PMID- 29592998
TI  - Gestational gigantomastia with spontaneous resolution in an Indian woman.
AB  - We present the case of a 20-year-old woman, primigravida with 24 weeks of
      amenorrhoea due to pregnancy. She came with symptoms of rapidly increasing size
      of both the breasts since 8 weeks. On examination, both breasts were grossly
      enlarged, right more than left, with the level of the nipples reaching beyond the
      level of the umbilicus. Breast circumference was measured to be 72 cm on the
      right, and left breast was 66 cm. No palpable lumps in both breasts. No axillary
      lymphadenopathy noted. Hormonal studies were found to be within the normal range.
      The pregnancy was terminated due to pre-eclampsia. The patient opted for regular
      follow-up and observation. While regularly following up, the size of both breasts
      was observed to gradually reduce to a circumference of 40 cm on the right and 30
      cm on the left.

PMID- 29592999
TI  - Treatment of refractory rheumatoid pleural effusion with abatacept.
AB  - Rheumatoid pleural effusion is generally responsive to corticosteroids, but
      refractory cases require consideration of second-line therapy. Here we report the
      case of a 61-year-old man with rheumatoid arthritis (RA) who developed a large
      right-sided pleural effusion and was successfully treated with abatacept.
      Thoracocentesis showed a sterile exudate and an elevated adenosine deaminase
      level. The methotrexate and etanercept used to treat the RA were withheld
      initially while he underwent a trial of prednisolone 40 mg/day for the pleural
      effusion. However, the effusion did not respond to this therapy. Thoracoscopic
      biopsy of the right pleura revealed fibrotic changes with lymphocyte infiltration
      mainly composed of CD4+ T cells and B cells but no evidence of malignancy or
      infection. The patient was started on abatacept and resumed methotrexate. The
      treatment was effective in our case. Abatacept should be considered as a
      treatment option in patients with refractory rheumatoid pleural effusion.

PMID- 29593001
TI  - Pemberton's sign in SVC syndrome from metastatic renal cell carcinoma.

PMID- 29593000
TI  - Diagnostic dilemma: think about anterior cutaneous nerve entrapment syndrome
      (ACNES) in patients with atypical abdominal pain and Crohn's disease.
AB  - Chronic abdominal pain can be a difficult diagnostic dilemma. Anterior cutaneous
      nerve entrapment syndrome (ACNES) is a potential differential diagnosis that
      should be considered because treatment is both easy and effective. We describe
      the case of a 51-year-old man presenting with 7 months of right lower quadrant
      abdominal pain on the background of known Crohn's disease. A circumspect surgical
      approach and multidisciplinary input was key to making the diagnosis of a nerve
      entrapment syndrome.

PMID- 29593002
TI  - Angioedema as the presenting feature of systemic lupus erythematosus.
AB  - A young female in her early 20s presented with low-grade fever for 1 month,
      puffiness of face and abdominal distension for 15 days. Evaluation revealed
      pancytopenia with normocellular marrow, hypocomplementaemia and Coomb's positive
      haemolytic anaemia. She had angioedema with laryngospasm and worsening facial
      oedema which had dramatic response to steroids. Further workup lead to a
      diagnosis of systemic lupus erythematosus with neuropsychiatric involvement.
      Treatment with pulse steroids and cyclophosphamide resulted in dramatic
      improvement of her symptoms with no recurrence of angioedema during her follow-up
      visits.

PMID- 29593003
TI  - Intraosseous ganglion cyst of the distal tibia: a rare entity in a rarer
      location.
AB  - Intraosseous ganglion cysts are rare entities, even rarer in the subchondral
      region of the distal tibia. A 20-year-old male presented to us with complaints of
      pain and limp in the right ankle joint, which was diagnosed as an intraosseous
      ganglion cyst of the right distal tibia and was successfully treated with
      curettage and bone cement with no recurrence seen even after a year.

PMID- 29593004
TI  - Giant coronary artery aneurysms in a 12-week-old infant with incomplete Kawasaki
      disease.
AB  - Kawasaki disease (KD) is an acute inflammatory vasculitis that occurs worldwide
      and disproportionately affects male children, most commonly between the ages of 6
      months and 5 years. KD can present with only a few features and thus be difficult
      to diagnose, particularly in the youngest and oldest patients. We describe a 12
      week-old Caucasian female infant who presented with rash and fever but no other
      features of KD, who developed giant coronary artery aneurysms. Considering how
      common is the presentation of a febrile infant with a rash, this case highlights
      the importance of considering KD early in the differential diagnosis for any
      infant with unexplained fever. Furthermore, it emphasises how echocardiography
      can help in the investigation of a febrile child with no clear source of
      infection.

PMID- 29593005
TI  - An unusual case of worsening cellulitis: baboon syndrome or SDRIFE.

PMID- 29593006
TI  - Purpura fulminans causing acute cortical necrosis in postpartum period.

PMID- 29593007
TI  - Subintimal intraplaque haemorrhage prior to aortic plaque rupture: 2-year
      angioscopic follow-up.

PMID- 29593008
TI  - Beau's lines.

PMID- 29593010
TI  - Differences in Breast Cancer Survival by Molecular Subtypes in the United States.
AB  - : Background: Although incidence rates of breast cancer molecular subtypes are
      well documented, effects of molecular subtypes on breast cancer-specific survival
      using the largest population coverage to date are unknown in the U.S. POPULATION:
      Methods: Using Surveillance, Epidemiology and End Results cancer registry data,
      we assessed survival after breast cancer diagnosis among women diagnosed during
      2010 to 2013 and followed through December 31, 2014. Breast cancer molecular
      subtypes defined by joint hormone receptor [HR, estrogen receptor (ER) and/or
      progesterone receptor (PR)] and HER2 status were assessed. Multiple imputation
      was used to fill in missing receptor status. Four-year breast cancer-specific
      survival per molecular subtypes and clinical/demographic factors were calculated.
      A Cox proportional hazards model was used to evaluate survival while controlling
      for clinical and demographic factors.Results: The best survival pattern was
      observed among women with HR+/HER2- subtype (survival rate of 92.5% at 4 years),
      followed by HR+/HER2+ (90.3%), HR-/HER2+ (82.7%), and finally worst survival for
      triple-negative subtype (77.0%). Notably, failing to impute cases with missing
      receptor status leads to overestimation of survival because those with missing
      receptor status tend to have worse prognostic features. Survival differed
      substantially by stage at diagnosis. Among de novo stage IV disease, women with
      HR+/HER2+ subtype experienced better survival than those with HR+/HER2- subtype
      (45.5% vs. 35.9%), even after controlling for other factors.Conclusions:
      Divergence of survival curves in stage IV HR+/HER2+ versus HR+/HER2- subtype is
      likely attributable to major advances in HER2-targeted treatment.Impact: Contrary
      to conventional thought, HR+/HER2+ subtype experienced better survival than
      HR+/HER2- in advanced-stage disease. Cancer Epidemiol Biomarkers Prev; 27(6); 619
      26. (c)2018 AACR.

PMID- 29593009
TI  - Stanniocalcin Expression as a Predictor of Late Breast Cancer Recurrence.
AB  - Background: Expression of human paracrine hormones stanniocalcin 1 (STC1) and
      stanniocalcin 2 (STC2) may potentiate late breast cancer recurrence. We tested
      the hypothesis that expression of STC1 and STC2 in primary breast tumors is more
      strongly associated with late versus early recurrences.Methods: A total of 541
      estrogen receptor-positive, tamoxifen-treated (ER+/TAM+) and 300 ER-negative,
      tamoxifen-untreated (ER-/TAM-) breast cancer patients who experienced recurrence
      within 10 years of primary diagnosis and matched recurrence-free controls were
      selected from a cohort of 11,251 Danish breast cancer patients diagnosed with
      stage I, II, or III breast cancer during 1985 to 2001. The association between
      IHC expression of STC1 and STC2 in primary breast tumor tissue microarrays and
      breast cancer recurrence was evaluated within median time to recurrence
      quintiles.Results: The association between STC1 expression, dichotomized as
      positive or negative, and recurrence was strongly positive for the final time
      quintile (6-10 years postdiagnosis) in the ER+/TAM+ group [aOR = 2.70; 95%
      confidence interval (CI): 1.22-5.98]. Regression of the log ORs relating
      dichotomous STC1 and STC2 expression to recurrence by median time to recurrence
      (year) resulted in a relatively large positive effect estimate for STC1 (beta =
      0.16; 95% CI, -0.03-0.36) and a near-null positive effect estimate for STC2 (beta
      = 0.04; 95% CI, -0.14-0.21).Conclusions: Our results suggest a stronger
      association between primary tumor STC1 expression and late recurrence, as opposed
      to early recurrence, although no clear trend was apparent.Impact: STC1 expression
      in the primary tumor may potentiate late recurrences, suggesting dormancy
      pathways that merit further investigation. Cancer Epidemiol Biomarkers Prev;
      27(6); 653-9. (c)2018 AACR.

PMID- 29593011
TI  - Rural Disparities in Treatment-Related Financial Hardship and Adherence to
      Surveillance Colonoscopy in Diverse Colorectal Cancer Survivors.
AB  - Background: Cancer survivors increasingly report financial hardship as a
      consequence of the high cost of cancer care, yet the financial experience of
      rural cancer survivors remains largely unstudied. The purpose of this study was
      to investigate potential rural disparities in the likelihood of financial
      hardship and nonadherence to surveillance colonoscopy.Methods: Individuals
      diagnosed with localized or regional colorectal cancer between 2004 and 2012 were
      ascertained by the population-based New Mexico Tumor Registry. Participants
      completed a mailed questionnaire or telephone survey about their colorectal
      cancer survivorship experience, including treatment-related financial hardship
      and receipt of surveillance colonoscopy. Multivariable logistic regression was
      used to estimate adjusted odds ratios (ORs) and 95% confidence intervals
      (CIs).Results: Compared with urban colorectal cancer survivors (n = 168), rural
      colorectal cancer survivors (n = 109) were slightly older; more likely to be
      married (65% vs. 59%) and have an annual income <$30,000 (37% vs. 27%); and less
      likely to be employed (35% vs. 41%), have a college degree (28% vs. 38%), or a
      high level of health literacy (39% vs. 51%). Rural survivors were twice as likely
      as urban survivors to report treatment-related financial hardship (OR, 1.86; 95%
      CI, 1.06-3.28) and nonadherence to surveillance colonoscopy guidelines (OR, 2.28;
      95% CI, 1.07-4.85). In addition, financial hardship was independently associated
      with nonadherence to surveillance colonoscopy (OR, 2.17; 95% CI, 1.01
      4.85).Conclusions: Substantial rural disparities in the likelihood of financial
      hardship and nonadherence to surveillance colonoscopy exist.Impact: Treatment
      related financial hardship among rural colorectal cancer survivors may negatively
      affect adherence to guideline-recommended follow-up care. Cancer Epidemiol
      Biomarkers Prev; 27(11); 1275-82. (c)2018 AACR.

PMID- 29593012
TI  - Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal
      Immunochemical Test and Age/Sex-Specific Thresholds for Test Positivity.
AB  - Background: Despite age and sex differences in fecal hemoglobin (f-Hb)
      concentrations, most fecal immunochemical test (FIT) screening programs use
      population-average cut-points for test positivity. The impact of age/sex-specific
      threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening
      are unknown.Methods: Using data from 723,113 participants enrolled in a Taiwanese
      population-based colorectal cancer screening with single FIT between 2004 and
      2009, sensitivity and specificity were estimated for various f-Hb thresholds for
      test positivity. This included estimates based on a "universal" threshold,
      receiver-operating-characteristic curve-derived threshold, targeted sensitivity,
      targeted false-positive rate, and a colonoscopy-capacity-adjusted method
      integrating colonoscopy workload with and without age/sex adjustments.Results:
      Optimal age/sex-specific thresholds were found to be equal to or lower than the
      universal 20 MUg Hb/g threshold. For older males, a higher threshold (24 MUg
      Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear
      relationship was observed between sensitivity and colonoscopy workload with
      workload rising disproportionately to sensitivity at 16 MUg Hb/g. At this
      "colonoscopy-capacity-adjusted" threshold, the test positivity (colonoscopy
      workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0%
      workload and a lower 78.7% sensitivity using 20 MUg Hb/g. When constrained on
      capacity, age/sex-adjusted estimates were generally lower. However, optimizing
      age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or
      greater compared with a universal threshold.Conclusions: Age/sex-specific
      thresholds improve FIT accuracy with modest increases in colonoscopy
      demand.Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds
      may be useful in optimizing individual screening programs based on detection
      accuracy, population characteristics, and clinical capacity. Cancer Epidemiol
      Biomarkers Prev; 27(6); 704-9. (c)2018 AACR.

PMID- 29593013
TI  - Relationship of Familial Hypercholesterolemia and High Low-Density Lipoprotein
      Cholesterol to Ischemic Stroke.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a condition with very high
      concentrations of low-density lipoprotein (LDL) cholesterol and high risk of
      ischemic heart disease including myocardial infarction. However, there is limited
      and contradictory information on whether FH and high LDL cholesterol per se
      confer high risk of ischemic stroke. We tested the hypotheses that individuals in
      the general population with FH and/or high LDL cholesterol have higher risk of
      ischemic stroke. METHODS: The associations of FH and high LDL cholesterol with
      ischemic stroke risk were tested in both causal, genetic, and observational
      analyses using 106 412 individuals from the CGPS (Copenhagen General Population
      Study; 2823 ischemic strokes and 3792 myocardial infarctions) and/or 10 372
      individuals from the CCHS (Copenhagen City Heart Study; 945 ischemic strokes and
      1142 myocardial infarctions). FH causative mutations were LDLR W23X(rs267607213),
      W66G(rs121908025) and W556S, and APOB R3500Q(rs5742904). A Mendelian
      randomization design tested whether high LDL cholesterol per se has a causal
      effect on ischemic stroke risk, using a combination of the FH causative mutations
      and common genetic variants associated with high LDL cholesterol. RESULTS: The
      cumulative incidences in individuals in the CGPS with and without FH causative
      mutations were similar for ischemic stroke ( P=0.50) but not for myocardial
      infarction ( P<0.001): at age 80 years, 4% and 7% of these individuals developed
      ischemic stroke and 20% and 8% myocardial infarction, with similar results in the
      CCHS. There was no association between clinical FH and ischemic stroke, except if
      personal premature ischemic heart disease was included in the clinical FH
      criteria. Ischemic heart disease at baseline was associated with higher ischemic
      stroke risk, explaining the higher ischemic stroke risk in those with high LDL
      cholesterol. For a 1 mmol/L higher LDL cholesterol, the genetic causal risk ratio
      was 1.11 (0.62-2.02) for ischemic stroke and 1.45 (1.08-1.93) for myocardial
      infarction. CONCLUSIONS: FH and high LDL cholesterol did not confer an increased
      risk of ischemic stroke. A positive association with ischemic stroke observed for
      some clinical FH criteria and high LDL cholesterol appears to be due to previous
      ischemic heart disease, rather than to high LDL cholesterol per se.

PMID- 29593014
TI  - Ryanodine Receptor Calcium Leak in Circulating B-Lymphocytes as a Biomarker in
      Heart Failure.
AB  - BACKGROUND: Advances in congestive heart failure (CHF) management depend on
      biomarkers for monitoring disease progression and therapeutic response. During
      systole, intracellular Ca2+ is released from the sarcoplasmic reticulum into the
      cytoplasm through type-2 ryanodine receptor/Ca2+ release channels. In CHF,
      chronically elevated circulating catecholamine levels cause pathological
      remodeling of type-2 ryanodine receptor/Ca2+ release channels resulting in
      diastolic sarcoplasmic reticulum Ca2+ leak and decreased myocardial
      contractility. Similarly, skeletal muscle contraction requires sarcoplasmic
      reticulum Ca2+ release through type-1 ryanodine receptors (RyR1), and chronically
      elevated catecholamine levels in CHF cause RyR1-mediated sarcoplasmic reticulum
      Ca2+ leak, contributing to myopathy and weakness. Circulating B-lymphocytes
      express RyR1 and catecholamine-responsive signaling cascades, making them a
      potential surrogate for defects in intracellular Ca2+ handling because of leaky
      RyR channels in CHF. METHODS: Whole blood was collected from patients with CHF,
      CHF following left-ventricular assist device implant, and controls. Blood was
      also collected from mice with ischemic CHF, ischemic CHF+S107 (a drug that
      specifically reduces RyR channel Ca2+ leak), and wild-type controls. Channel
      macromolecular complex was assessed by immunostaining RyR1 immunoprecipitated
      from lymphocyte-enriched preparations. RyR1 Ca2+ leak was assessed using flow
      cytometry to measure Ca2+ fluorescence in B-lymphocytes in the absence and
      presence of RyR1 agonists that empty RyR1 Ca2+ stores within the endoplasmic
      reticulum. RESULTS: Circulating B-lymphocytes from humans and mice with CHF
      exhibited remodeled RyR1 and decreased endoplasmic reticulum Ca2+ stores,
      consistent with chronic intracellular Ca2+ leak. This Ca2+ leak correlated with
      circulating catecholamine levels. The intracellular Ca2+ leak was significantly
      reduced in mice treated with the Rycal S107. Patients with CHF treated with left
      ventricular assist devices exhibited a heterogeneous response. CONCLUSIONS: In
      CHF, B-lymphocytes exhibit remodeled leaky RyR1 channels and decreased
      endoplasmic reticulum Ca2+ stores consistent with chronic intracellular Ca2+
      leak. RyR1-mediated Ca2+ leak in B-lymphocytes assessed using flow cytometry
      provides a surrogate measure of intracellular Ca2+ handling and systemic
      sympathetic burden, presenting a novel biomarker for monitoring response to
      pharmacological and mechanical CHF therapy.

PMID- 29593015
TI  - An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein
      Cholesterol Levels.
AB  - BACKGROUND: Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a
      major risk factor for cardiovascular disease via its contribution to the
      development and progression of atherosclerotic lesions. Although the genetic
      basis of LDL-C has been studied extensively, currently known genetic variants
      account for only ~20% of the variation in LDL-C levels. METHODS: Through an array
      based association analysis in 1102 Amish subjects, we identified a variant
      strongly associated with LDL-C levels. Using a combination of genetic analyses,
      zebrafish models, and in vitro experiments, we sought to identify the causal gene
      driving this association. RESULTS: We identified a founder haplotype associated
      with a 15 mg/dL increase in LDL-C on chromosome 5. After recombination mapping,
      the associated region contained 8 candidate genes. Using a zebrafish model to
      evaluate the relevance of these genes to cholesterol metabolism, we found that
      expression of the transcribed pseudogene, APOOP1, increased LDL-C and vascular
      plaque formation. CONCLUSIONS: Based on these data, we propose that APOOP1
      regulates levels of LDL-C in humans, thus identifying a novel mechanism of lipid
      homeostasis.

PMID- 29593016
TI  - GCAT|Genomes for life: a prospective cohort study of the genomes of Catalonia.
AB  - PURPOSE: The prevalence of chronic non-communicable diseases (NCDs) is increasing
      worldwide. NCDs are the leading cause of both morbidity and mortality, and it is
      estimated that by 2030, they will be responsible for 80% of deaths across the
      world. The Genomes for Life (GCAT) project is a long-term prospective cohort
      study that was designed to integrate and assess the role of epidemiological,
      genomic and epigenomic factors in the development of major chronic diseases in
      Catalonia, a north-east region of Spain. PARTICIPANTS: At the end of 2017, the
      GCAT Study will have recruited 20 000 participants aged 40-65 years. Participants
      who agreed to take part in the study completed a self-administered computer
      driven questionnaire, and underwent blood pressure, cardiac frequency and
      anthropometry measurements. For each participant, blood plasma, blood serum and
      white blood cells are collected at baseline. The GCAT Study has access to the
      electronic health records of the Catalan Public Healthcare System. Participants
      will be followed biannually at least 20 years after recruitment. FINDINGS TO
      DATE: Among all GCAT participants, 59.2% are women and 83.3% of the cohort
      identified themselves as Caucasian/white. More than half of the participants have
      higher education levels, 72.2% are current workers and 42.1% are classified as
      overweight (body mass index >=25 and <30 kg/m2). We have genotyped 5459
      participants, of which 5000 have metabolome data. Further, the whole genome of
      808 participants will be sequenced by the end of 2017. FUTURE PLANS: The first
      follow-up study started in December 2017 and will end by March 2018. Residences
      of all subjects will be geocoded during the following year. Several genomic
      analyses are ongoing, and metabolomic and genomic integrations will be performed
      to identify underlying genetic variants, as well as environmental factors that
      influence metabolites.

PMID- 29593017
TI  - Electroacupuncture plus standard of care for managing refractory functional
      dyspepsia: protocol of a pragmatic trial with economic evaluation.
AB  - INTRODUCTION: This trial proposes to compare the effectiveness and cost
      effectiveness of electroacupuncture (EA) plus on-demand gastrocaine with waiting
      list for EA plus on-demand gastrocaine in providing symptom relief and quality-of
      life improvement among patients with functional dyspepsia (FD). METHODS AND
      ANALYSIS: This is a single-centre, pragmatic, randomised parallel-group,
      superiority trial comparing the outcomes of (1) EA plus on-demand gastrocaine
      group and (2) waiting list to EA plus on-demand gastrocaine group. 132 (66/arm)
      endoscopically confirmed, Helicobacter pylori-negative patients with FD will be
      recruited. Enrolled patients will respectively be receiving (1) 20 sessions of EA
      over 10 weeks plus on-demand gastrocaine; or (2) on-demand gastrocaine and being
      nominated on to a waiting list for EA, which entitles them 20 sessions of EA over
      10 weeks after 12 weeks of waiting. The primary outcome will be the between-group
      difference in proportion of patients achieving adequate relief of symptoms over
      12 weeks. The secondary outcomes will include patient-reported change in global
      symptoms and individual symptoms, Nepean Dyspepsia Index, Nutrient Drink Test, 9
      item Patient Health Questionnaire (PHQ9), and 7-item Generalised Anxiety Disorder
      Scale (GAD7). Adverse events will be assessed formally. Results on direct medical
      costs and on the EuroQol (EQ-5D) questionnaire will also be used to assess cost
      effectiveness. Analysis will follow the intention-to-treat principle using
      appropriate univariate and multivariate methods. A mixed model analysis taking
      into account missing data of these outcomes will be performed. Cost-effectiveness
      analysis will be performed using established approach. ETHICS AND DISSEMINATION:
      The study is supported by the Health and Medical Research Fund, Government of the
      Hong Kong Special Administrative Region of China. It has been approved by the
      Joint Chinese University of Hong Kong - New Territories East Cluster Clinical
      Research Ethics Committee. Results will be published in peer-reviewed journals
      and be disseminated in international conference. TRIAL REGISTRATION NUMBER:
      ChiCTR-IPC-15007109; Pre-result.

PMID- 29593018
TI  - Randomised controlled trial of rhinothermy for treatment of the common cold: a
      feasibility study.
AB  - OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of
      rhinothermy for the common cold. DESIGN: Open label, randomised, controlled
      feasibility study. SETTING: Single-centre research institute in New Zealand
      recruiting participants from the community. PARTICIPANTS: 30 adult participants
      with symptoms of a common cold, presenting within 48 hours of the onset of
      symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive
      either 35 L/min of 100% humidified air at 41 degrees C via high flow nasal
      cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg
      daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary
      outcome was the proportion of screened candidates who were randomised. Secondary
      outcomes included: proportion of randomised participants who completed the study;
      modified Jackson scores from randomisation to 10 days after initiation of
      randomised regimen; time until feeling 'a lot better' compared with study entry;
      time until resolution of symptoms or symptom score at 10 days postrandomisation;
      proportion of organisms identified by PCR analysis of nasal swabs taken at
      baseline; the patterns of use of the rhinothermy device; estimated adherence of
      the control group; and rhinothermy device tolerability. RESULTS: In all 30/79
      (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were
      randomised. Rhinothermy was well tolerated, and all randomised participants
      completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in
      the modified Jackson score was greater with rhinothermy compared with control at
      days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (-6.4, 95% CI -9.4 to
      -3.3). The substantial clinical benefit threshold for modified Jackson score was
      a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy
      compared with low-dose vitamin C in the treatment of the common cold is feasible.
      TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results.

PMID- 29593019
TI  - Recruitment for exercise or physical activity interventions: a protocol for
      systematic review.
AB  - INTRODUCTION: Recruiting participants into research trials is essential for the
      advancement of scientific knowledge that depends on clinical research studies.
      For the field of exercise and physical activity, there is an added difficulty in
      recruiting participants because participants must be willing to participate in an
      intervention that requires a significant commitment of both time and physical
      effort. Therefore, we have planned a systematic review to analyse how
      methodological factors, intervention characteristics and participant demographics
      impact recruitment rates in specific populations. This information will help
      researchers improve the design and recruitment approach in future studies.
      METHODS AND ANALYSIS: A mixed methods systematic review will be performed on
      studies that implement physical activity interventions and present data on
      participant recruitment. We plan on searching the Pubmed, Cumulative Index to
      Nursing and Allied Health Literature and Online Resource for Recruitment research
      in Clinical Trials databases for potentially eligible articles from database
      inception through 10 February 2017. A standardised approach will be used to
      identify studies through a review of titles, abstracts and reference lists. The
      process for each eligible study is to determine their eligibility, extract data
      from eligible studies and rate each eligible study's methodological quality.
      Exploratory multivariate regression models will be used to determine the effects
      of methodological factors, intervention characteristics and participant
      demographics on the recruitment variables of interest. ETHICS AND DISSEMINATION:
      Because all of the data used in this systematic review has been published, this
      review does not require ethical approval. The results of this review will be
      disseminated through peer-reviewed publication as well as through conference
      presentations. PROSPERO REGISTRATION NUMBER: CRD42017057284.

PMID- 29593020
TI  - Ethnic differences in the progression of chronic kidney disease and risk of death
      in a UK diabetic population: an observational cohort study.
AB  - OBJECTIVE: To determine ethnic differences in the progression of chronic kidney
      disease (CKD) and risk of end-stage renal failure (ESRF) and death in adults with
      type 2 diabetes mellitus (T2DM), and to identify predictors of rapid renal
      decline. DESIGN: Observational community-based cohort study undertaken from 2006
      to 2016 with nested case-control study. SETTING: 135 inner London primary care
      practices contributing to the east London Database. PARTICIPANTS: General
      practice-registered adults aged 25-85 years with established T2DM and CKD at
      baseline. OUTCOMES: The annual rate of renal decline was compared between white,
      south Asian and black groups, and stratified by proteinuria and raised blood
      pressure (BP) at baseline. Predictors of rapid renal decline were identified in a
      nested case-control study. Cox proportional hazards regression was used to
      determine ethnic differences in the risk of ESRF and death. RESULTS: Age-sex
      adjusted annual decline was greatest in the Bangladeshi population. There was
      stepwise increase in the rate of decline when stratifying the cohort by baseline
      proteinuria and BP control, with south Asian groups being most sensitive to the
      combined effect of proteinuria and raised BP after accounting for key
      confounders.The odds of rapid renal decline were increased for individuals of
      Bangladeshi, African and Caribbean ethnicity, those with hypertension,
      proteinuria, cardiovascular disease and with increasing duration of diabetes.
      Rapid progression was more frequent in younger age groups. Risk of developing
      ESRF was highest in the black group compared with the white group (HR 1.88, 95%
      CI 1.11 to 3.19). Risk of death from any cause was 29% lower in the south Asian
      group compared with the white group (HR 0.71, 95% CI 0.56 to 0.91). CONCLUSIONS:
      Proteinuria and hypertension trigger accelerated estimated glomerular filtration
      rate decline differentially by ethnicity. Active monitoring of younger adults,
      who have greater odds of rapid progression and the most to gain from
      interventions, is essential.

PMID- 29593021
TI  - Lifestyle advice to cancer survivors: a qualitative study on the perspectives of
      health professionals.
AB  - OBJECTIVES: Adoption of healthy lifestyle behaviours has shown promising
      effectiveness in reducing the high morbidity burden of cancer survivors. Health
      professionals (HPs) are well suited to provide lifestyle advice but few survivors
      report receiving guidance from them. This study aimed to explore HPs' perspective
      of lifestyle advice (on healthy eating, physical activity, smoking, and alcohol)
      for cancer survivors. DESIGN: In-depth semistructured qualitative interviews were
      conducted by telephone or face to face. Data were analysed using qualitative
      content analysis. SETTING AND PARTICIPANTS: Twenty-one UK HPs working in
      secondary care with breast, prostate or colorectal cancer survivors were
      interviewed. RESULTS: The overarching theme was that HPs' desire to provide
      lifestyle advice was not necessarily matched by knowledge and action. Three main
      themes were identified: (1) survivorship-centred barriers to provision, (2) HP
      centred barriers to provision, and (3) optimal delivery of lifestyle advice.
      Results suggested that HPs' perceptions of survivors' current status of
      practising health behaviours, their perceived socioeconomic barriers and ability
      to practise health behaviours, and HPs' fear for potential loss of connection
      with the patient influenced provision of lifestyle advice. Further factors
      included HPs' knowledge of healthy lifestyle guidelines, feeling that they were
      not the 'right person' to provide advice, and lack of time and resources. HPs
      stressed that the optimal delivery of lifestyle advice should (1) be tailored to
      the individual and delivered throughout the cancer journey, (2) be focused on
      small and achievable changes framed as part of their treatment regimen and (3) be
      cost-effective for wide-scale implementation. CONCLUSIONS: Incorporation of the
      identified barriers when developing HP training programmes and lifestyle
      interventions could increase the probability of successful behavioural change,
      and thus improve outcomes for cancer survivors.

PMID- 29593022
TI  - Hospital at Home care for older patients with cognitive impairment: a protocol
      for a randomised controlled feasibility trial.
AB  - INTRODUCTION: An acute hospital admission is a stressful life event for older
      people, particularly for those with cognitive impairment. The hospitalisation is
      often complicated by hospital-associated geriatric syndromes, including delirium
      and functional loss, leading to functional decline and nursing home admission.
      Hospital at Home care aims to avoid hospitalisation-associated adverse outcomes
      in older patients with cognitive impairment by providing hospital care in the
      patient's own environment. METHODS AND ANALYSIS: This randomised, non-blinded
      feasibility trial aims to assess the feasibility of conducting a randomised
      controlled trial in terms of the recruitment, use and acceptability of Hospital
      at Home care for older patients with cognitive impairment. The quality of care
      will be evaluated and the advantages and disadvantages of the Hospital at Home
      care programme compared with usual hospital care. Eligible patients will be
      randomised either to Hospital at Home care in their own environment or usual
      hospital care. The intervention consists of hospital level care provided at
      patients' homes, including visits from healthcare professionals, diagnostics
      (laboratory tests, blood cultures) and treatment. The control group will receive
      usual hospital care. Measurements will be conducted at baseline, during
      admission, at discharge and at 3 and 6 months after the baseline assessment.
      ETHICS AND DISSEMINATION: Institutional ethics approval has been granted. The
      findings will be disseminated through public lectures, professional and
      scientific conferences, as well as peer-reviewed journal articles. The study
      findings will contribute to knowledge on the implementation of Hospital at Home
      care for older patients with cognitive disorders. The results will be used to
      inform and support strategies to deliver eligible care to older patients with
      cognitive impairment. TRIAL REGISTRATION NUMBER: e020313; Pre-results.

PMID- 29593023
TI  - Migraine and the risk of cardiovascular and cerebrovascular events: a meta
      analysis of 16 cohort studies including 1 152 407 subjects.
AB  - OBJECTIVES: To perform an updated meta-analysis to evaluate the long-term
      cardiovascular and cerebrovascular outcomes among migraineurs. SETTING: A meta
      analysis of cohort studies performed according to the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: The MEDLINE,
      Web of Science and Cochrane Central Register of Controlled Trials databases were
      searched for relevant articles. PARTICIPANTS: A total of 16 cohort studies (18
      study records) with 394 942 migraineurs and 757 465 non-migraineurs were
      analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Major adverse cardiovascular
      and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non
      specified), myocardial infarction (MI) and all-cause mortality. The outcomes were
      reported at the longest available follow-up. DATA ANALYSIS: Summary-adjusted
      hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard
      model. The risk of bias was assessed by the Newcastle-Ottawa Scale. RESULTS:
      Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95%
      confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk
      of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI
      (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference
      in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10,
      P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between
      the studies. The presence of aura was an effect modifier for stroke (adjusted HR
      aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31,
      P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12
      to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001).
      CONCLUSION: Migraine headache was associated with an increased long-term risk of
      cardiovascular and cerebrovascular events. This effect was due to an increased
      risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to
      severe degree of heterogeneity for the outcomes, which was partly explained by
      the presence of aura. PROSPERO REGISTRATION NUMBER: CRD42016052460.

PMID- 29593024
TI  - Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral
      Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional
      study.
AB  - INTRODUCTION: Cerebral autoregulation (CA) is impaired in a multitude of
      neurological conditions. Increasingly, clinical studies are correlating the
      nature of this impairment with prognostic markers. In acute intracerebral
      haemorrhage (ICH), impairment of CA has been associated with worsening clinical
      outcomes including poorer Glasgow Coma Score and larger haematoma volume.
      Hypocapnia has been shown to improve CA despite concerns over hypoperfusion and
      consequent ischaemic risks, and it is therefore hypothesised that hypocapnia (via
      hyperventilation) in acute ICH may improve CA and consequently clinical outcome.
      BREATHE-ICH is a CA-targeted interventional study in acute ICH utilising a simple
      bedside hyperventilatory manoeuvre. METHODS AND ANALYSIS: Patients with acute ICH
      within 48 hours of onset will be included. The experimental set-up measures
      cerebral blood flow (cerebral blood velocity, transcranial Doppler), blood
      pressure (Finometer) and end tidal carbon dioxide (capnography) at baseline, and
      in response to hypocapnia (-5 mm and -10 mm Hg below baseline) achieved via a 90
      s hyperventilatory manoeuvre. Autoregulation is evaluated with transfer function
      analysis and autoregulatory index calculations. Important classical endpoints
      associated with this before and after interventional study include death and
      disability at 14 days and the proportion of recruited individuals able to comply
      with the full measurement protocol. ETHICS AND DISSEMINATION: A favourable
      opinion was granted by the East Midlands-Nottingham 1 Research Ethics Committee
      (17/EM/0283). It is anticipated that the results of this study will be presented
      at national and international meetings, with reports being published in journals
      during late 2018. TRIAL REGISTRATION NUMBER: NCT03324321.

PMID- 29593025
TI  - Self-reported body silhouette trajectories across the lifespan and excessive
      daytime sleepiness in adulthood: a retrospective analysis. The Paris Prospective
      Study III.
AB  - OBJECTIVES: Excessive daytime sleepiness (EDS) is a common sleep complaint in the
      population and is increasingly recognised as deleterious for health. Simple and
      sensitive tools allowing identifying individuals at greater risk of EDS would be
      of public health importance. Hence, we determined trajectories of body silhouette
      from early childhood to adulthood and evaluated their association with EDS in
      adulthood. DESIGN: A retrospective analysis in a prospective community-based
      study. PARTICIPANTS: 6820 men and women self-reported their silhouette at ages 8,
      15, 25, 35 and 45 using the body silhouettes proposed by Stunkard et al. EDS was
      defined by an Epworth Sleepiness Scale score >=11. MAIN OUTCOME MEASURE: Presence
      of EDS in adulthood. RESULTS: The study population comprised 6820 participants
      (mean age 59.8 years, 61.1% men). Five distinct body silhouettes trajectories
      over the lifespan were identified: 31.9% 'lean stable', 11.1% 'lean increase',
      16.1% 'lean-marked increase', 32.5% 'moderate stable' and 8.4% 'heavy stable'.
      Subjects with a 'heavy-stable' trajectory (OR 1.24, 95% CI 0.94 to 1.62) and
      those with a 'lean-marked increase' trajectory (OR 1.46, 95% CI 1.18 to 1.81)
      were more likely to have EDS when compared with the 'lean-stable' group after
      adjusting for confounding. Further adjustment for birth weight strengthened the
      magnitude of the ORs. CONCLUSION: Increasing body silhouette and to a lesser
      extent constantly high body silhouette trajectory from childhood to adulthood are
      associated with increased likelihood of EDS, independently of major confounding
      variables. TRIAL REGISTRATION NUMBER: NCT00741728; Pre-results.

PMID- 29593026
TI  - Impacts of smoke-free public places legislation on inequalities in youth smoking
      uptake: study protocol for a secondary analysis of UK survey data.
AB  - INTRODUCTION: Smoke-free public places legislation has been introduced in many
      countries to protect the public from the harmful effects of secondhand smoking.
      While evaluations of smoke-free policies have demonstrated major public health
      benefits, the impact on youth smoking and inequalities in smoking remains
      unclear. This project aims to evaluate how smoke-free public places legislation
      in the UK has impacted on inequalities in youth smoking uptake, and how much of
      any impact is via changes in parental smoking behaviour. METHODS AND ANALYSIS:
      The study will constitute secondary analyses of UK data (from the British
      Household Panel Survey and the Understanding Society study). Merging these
      datasets gives coverage of the period from 1994 to 2016. Missing data will be
      handled using multiple imputation. The primary outcomes are the rates and
      inequalities in initiation, experimentation, escalation to daily smoking and
      quitting among youths aged 11-15 years. Secondary outcomes include the prevalence
      of smoking among parents of these youths. Discrete-time event history analysis
      will be conducted to examine whether changes in the probability of youth smoking
      transitions are associated with the implementation of the smoke-free public
      places legislation; and whether any observed effects differ by socioeconomic
      position and parental smoking. A multilevel logistic regression model will be
      used to investigate whether there is a step change or change in trend for the
      prevalence of parental smoking after the policy was implemented. The models will
      be adjusted for relevant factors (including cigarette taxation, the change in the
      legal age for purchase of cigarettes and e-cigarette prevalence) that may be
      associated with the implementation of the legislation. ETHICS AND DISSEMINATION:
      This project will use anonymised survey data which have been collected following
      independent ethical review. The dissemination of the study findings will adopt
      multiple communication channels targeting both scientific and non-scientific
      audiences.

PMID- 29593028
TI  - 5-Fluorouracil Enhances Protoporphyrin IX Accumulation and Lesion Clearance
      during Photodynamic Therapy of Actinic Keratoses: A Mechanism-Based Clinical
      Trial.
AB  - Purpose: Actinic keratoses (AK) are precancerous lesions that can progress to
      squamous cell carcinoma. Photodynamic therapy (PDT) and topical 5-fluorouracil
      (5FU) are commonly used agents for AK. Empirical reports suggest that combining
      them can improve the therapeutic response. However, the optimal combined regimen
      was not clear in terms of proper sequence, timing, and mechanism. This clinical
      study explored mechanisms of action for neoadjuvantal 5FU and PDT for treatment
      of AK.Patients and Methods: A bilaterally controlled trial (17 patients) was
      performed. One side of the body (face, scalp, forearms) received 5FU pretreatment
      for 6 days, whereas the other side served as no-pretreatment control.
      Methylaminolevulinate cream was applied to both sides for 3 hours, and
      protoporphyrin IX (PpIX) levels were measured by noninvasive fluorimetry and skin
      biopsy. After red light illumination, lesion clearance was assessed at 3, 6, 9,
      and 12 months after PDT.Results: PpIX levels were increased 2- to 3-fold in 5FU
      pretreated lesions versus controls. Altered expression of heme-synthetic enzymes
      (coproporphyrinogen oxidase and ferrochelatase) and induction of p53 were
      observed, probably accounting for increased PpIX and subsequent cancer cell
      death. Relative clearance rates after PDT with or without 5FU pretreatment were
      75% versus 45% at 3 months, and 67% versus 39% at 6 months, respectively; these
      differences were statistically significant.Conclusions: Serial 5FU and PDT
      improve AK clearance by at least two mechanisms, enhanced photosensitizer
      accumulation and p53 induction. Because 5FU and PDT are FDA-approved modalities,
      the combined regimen can be readily employed in clinical practice to reduce AK
      burden and reduce SCC risk. Clin Cancer Res; 24(13); 3026-35. (c)2018 AACR.

PMID- 29593027
TI  - T-cell Dysfunction in Glioblastoma: Applying a New Framework.
AB  - A functional, replete T-cell repertoire is an integral component to adequate
      immune surveillance and to the initiation and maintenance of productive antitumor
      immune responses. Glioblastoma (GBM), however, is particularly adept at
      sabotaging antitumor immunity, eliciting severe T-cell dysfunction that is both
      qualitative and quantitative. Understanding and countering such dysfunction are
      among the keys to harnessing the otherwise stark potential of anticancer immune
      based therapies. Although T-cell dysfunction in GBM has been long described,
      newer immunologic frameworks now exist for reclassifying T-cell deficits in a
      manner that better permits their study and reversal. Herein, we divide and
      discuss the various T-cell deficits elicited by GBM within the context of the
      five relevant categories: senescence, tolerance, anergy, exhaustion, and
      ignorance. Categorization is appropriately made according to the molecular bases
      of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode
      of T-cell dysfunction and discuss the emerging immunotherapeutic strategies
      designed to overcome them. Clin Cancer Res; 24(16); 3792-802. (c)2018 AACR.

PMID- 29593029
TI  - Genetic Dissection of a Supergene Implicates Tfap2a in Craniofacial Evolution of
      Threespine Sticklebacks.
AB  - In nature, multiple adaptive phenotypes often coevolve and can be controlled by
      tightly linked genetic loci known as supergenes. Dissecting the genetic basis of
      these linked phenotypes is a major challenge in evolutionary genetics. Multiple
      freshwater populations of threespine stickleback fish (Gasterosteus aculeatus)
      have convergently evolved two constructive craniofacial traits, longer branchial
      bones and increased pharyngeal tooth number, likely as adaptations to dietary
      differences between marine and freshwater environments. Prior QTL mapping showed
      that both traits are partially controlled by overlapping genomic regions on
      chromosome 21 and that a regulatory change in Bmp6 likely underlies the tooth
      number QTL. Here, we mapped the branchial bone length QTL to a 155 kb, eight-gene
      interval tightly linked to, but excluding the coding regions of Bmp6 and
      containing the candidate gene Tfap2a Further recombinant mapping revealed this
      bone length QTL is separable into at least two loci. During embryonic and larval
      development, Tfap2a was expressed in the branchial bone primordia, where allele
      specific expression assays revealed the freshwater allele of Tfap2a was expressed
      at lower levels relative to the marine allele in hybrid fish. Induced loss-of
      function mutations in Tfap2a revealed an essential role in stickleback
      craniofacial development and show that bone length is sensitive to Tfap2a dosage
      in heterozygotes. Combined, these results suggest that closely linked but
      genetically separable changes in Bmp6 and Tfap2a contribute to a supergene
      underlying evolved skeletal gain in multiple freshwater stickleback populations.

PMID- 29593030
TI  - Stem Cell Properties of Normal Human Keratinocytes Determine Transformation
      Responses to Human Papillomavirus 16 DNA.
AB  - Human papillomavirus (HPV) infection of the genital tract is common; however,
      only about 10 to 15% of infections persist, and approximately 10 to 15% of these
      persistent infections result in cancer. Basal epidermal stem cells are the
      presumed target cells for HPV infection, providing a reservoir of latently
      infected cells that persist over time and initiate lesions. However, it is not
      known whether stem cell density has any influence on transformation of human
      keratinocytes by HPV. We explored the relationship between stem cell properties
      of normal human keratinocytes and their susceptibility to transformation by HPV16
      DNA. Normal human keratinocyte isolates (NHKc) derived from different donors were
      cultured in three-dimensional anchorage-free suspension to assess their spheroid
      forming ability. NHKc spheroids were then plated back into plastic monolayer
      culture and transfected with full-length HPV16 DNA, which we have previously
      shown to integrate into the host cell genome upon transfection. Spheroid-derived
      NHKc (SD-NHKc) and fluorescence-activated cell sorting-purified populations of
      basal stem-like keratinocytes, expressing low levels of epidermal growth factor
      receptor and high levels of integrin alpha 6 (EGFRlo/ITGalpha6hi), responded to
      transfection with HPV16 DNA with more vigorous proliferation, greater
      immortalization efficiency, and faster progression to differentiation resistance
      than autologous mass-cultured cells. Conversely, cells committed to terminal
      differentiation (EGFRhi/ITGalpha6lo) grew slowly after transfection with HPV16
      and failed to generate immortalized or DR clones. HPV16 DNA induced stem cell
      properties in mass-cultured NHKc. We conclude that HPV16 preferentially
      immortalizes basal keratinocytes with stem cell properties and that these cells
      readily achieve a differentiation-resistant phenotype upon immortalization by
      HPV16.IMPORTANCE This paper explores the relationship between the stem cell
      properties of normal human epidermal cells in culture and these cells'
      susceptibility to transformation by HPV16 DNA, the HPV type present in about 50%
      of cervical cancers. We report variable susceptibilities to HPV16-mediated
      transformation among different keratinocyte isolates derived from neonatal
      foreskin. Our findings provide strong experimental evidence that HPV16
      preferentially transforms basal keratinocytes with stem cell properties. Insights
      gained from these studies increase our understanding of the host cell-specific
      factors influencing individual susceptibility to HPV-driven transformation and
      the contributing factors leading to preneoplastic and neoplastic progression of
      HPV-positive lesions.

PMID- 29593031
TI  - Central Role of the NF-kappaB Pathway in the Scgb1a1-Expressing Epithelium in
      Mediating Respiratory Syncytial Virus-Induced Airway Inflammation.
AB  - Lower respiratory tract infection with respiratory syncytial virus (RSV) produces
      profound inflammation. Despite an understanding of the role of adaptive immunity
      in RSV infection, the identity of the major sentinel cells initially triggering
      inflammation is controversial. Here we evaluate the role of nonciliated
      secretoglobin (Scgb1a1)-expressing bronchiolar epithelial cells in RSV infection.
      Mice expressing a tamoxifen (TMX)-inducible Cre recombinase-estrogen receptor
      fusion protein (CreERTM) knocked into the Scgb1a1 locus were crossed with mice
      that harbor a RelA conditional allele (RelAfl ), with loxP sites flanking exons 5
      to 8 of the Rel homology domain. The Scgb1a1CreERTM/+ * RelAfl/fl mouse is a RelA
      conditional knockout (RelACKO) of a nonciliated epithelial cell population
      enriched in the small bronchioles. TMX-treated RelACKO mice have reduced
      pulmonary neutrophilic infiltration and impaired expression and secretion of NF
      kappaB-dependent cytokines in response to RSV. In addition, RelACKO mice had
      reduced expression levels of interferon (IFN) regulatory factor 1/7 (IRF1/7) and
      retinoic acid-inducible gene I (RIG-I), components of the mucosal IFN positive
      feedback loop. We demonstrate that RSV replication induces RelA to complex with
      bromodomain-containing protein 4 (BRD4), a cofactor required for RNA polymerase
      II (Pol II) phosphorylation, activating the atypical histone acetyltransferase
      (HAT) activity of BRD4 required for phospho-Ser2 Pol II formation, histone H3K122
      acetylation, and cytokine secretion in vitro and in vivo TMX-treated RelACKO mice
      have less weight loss and reduced airway obstruction/hyperreactivity yet similar
      levels of IFN-gamma production despite higher levels of virus production. These
      data indicate that the nonciliated Scgb1a1-expressing epithelium is a major
      innate sensor for restricting RSV infection by mediating neutrophilic
      inflammation and chemokine and mucosal IFN production via the RelA-BRD4
      pathway.IMPORTANCE RSV infection is the most common cause of infant
      hospitalizations in the United States, resulting in 2.1 million children annually
      requiring medical attention. RSV primarily infects nasal epithelial cells,
      spreading distally to produce severe lower respiratory tract infections. Our
      study examines the role of a nonciliated respiratory epithelial cell population
      in RSV infection. We genetically engineered a mouse that can be selectively
      depleted of the NF-kappaB/RelA transcription factor in this subset of epithelial
      cells. These mice show an impaired activation of the bromodomain-containing
      protein 4 (BRD4) coactivator, resulting in reduced cytokine expression and
      neutrophilic inflammation. During the course of RSV infection, epithelial RelA
      depleted mice have reduced disease scores and airway hyperreactivity yet
      increased levels of virus replication. We conclude that RelA-BRD4 signaling in
      nonciliated bronchiolar epithelial cells mediates neutrophilic airway
      inflammation and disease severity. This complex is an attractive target to reduce
      the severity of infection.

PMID- 29593032
TI  - Extracellular conformational changes in the capsid of human papillomaviruses
      contribute to asynchronous uptake into host cells.
AB  - The human papillomavirus type 16 (HPV16) is the leading cause of cervical cancer.
      For initial infection, HPV16 utilizes a novel endocytic pathway for host cell
      entry. Unique amongst viruses, uptake occurs asynchronously over a protracted
      period of time with half-times between 9-12 h. To trigger endocytic uptake, the
      virus particles need to undergo a series of structural modifications after
      initial binding to heparan sulfate proteoglycans (HSPG). These changes involve
      proteolytic cleavage of the major capsid protein L1 by kallikrein-8 (KLK8),
      exposure of the N-terminus of the minor capsid protein L2 by cyclophilins, and
      cleavage of this N-terminus by furin. Overall, the structural changes are thought
      to facilitate the engagement of an elusive secondary receptor for
      internalization. Here, we addressed whether structural changes are the rate
      limiting steps during infectious internalization of HPV16 by using structurally
      primed HPV16 particles. Our findings indicate that the structural modifications
      mediated by cyclophilins and furin, which lead to exposure and cleavage of the L2
      N-terminus, respectively, contribute to the slow and asynchronous internalization
      kinetics, whereas conformational changes elicited by HSPG binding and KLK8
      cleavage did not. However, these structural modifications only accounted for 30
      50% of the delay in internalization. Therefore, we propose that limited
      internalization receptor availability for engagement of HPV16 causes slow and
      asynchronous internalization in addition to rate-limiting structural changes in
      the viral capsid.IMPORTANCE HPVs are the main cause for anogenital cancers. Their
      unique biology is linked to the differentiation program of skin or mucosa. Here,
      we analyzed another unique aspect of HPV infections using the prototype HPV16.
      After initial cell binding, HPVs display an unusually protracted residence time
      on the plasma membrane prior to asynchronous uptake. As viruses typically do not
      expose themselves to host immune sensing, we analyzed the underlying reasons for
      this unusual behavior. This study provides evidence that both extracellular
      structural modifications and possibly a limited availability of the
      internalization receptor contribute to the slow internalization process of the
      virus. These findings indicated that perhaps a unique niche for initial infection
      exists that could allow for rapid infection. In addition, our results may help to
      develop novel, preventive antiviral measures.

PMID- 29593034
TI  - Deaminase-Dead Mouse APOBEC3 Is an In Vivo Retroviral Restriction Factor.
AB  - The apolipoprotein B editing complex 3 (APOBEC3) proteins are potent retroviral
      restriction factors that are under strong positive selection, both in terms of
      gene copy number and sequence diversity. A common feature of all the members of
      the APOBEC3 family is the presence of one or two cytidine deamination domains,
      essential for cytidine deamination of retroviral reverse transcripts as well as
      packaging into virions. Several studies have indicated that human and mouse
      APOBEC3 proteins restrict retrovirus infection via cytidine deaminase (CD)
      dependent and -independent means. To understand the relative contribution of CD
      independent restriction in vivo, we created strains of transgenic mice on an
      APOBEC3 knockout background that express a deaminase-dead mouse APOBEC3 due to
      point mutations in both CD domains (E73Q/E253Q). Here, we show that the CD-dead
      APOBEC3 can restrict murine retroviruses in vivo Moreover, unlike the wild-type
      protein, the mutant APOBEC3 is not packaged into virions but acts only as a cell
      intrinsic restriction factor that blocks reverse transcription by incoming
      viruses. Finally, we show that wild-type and CD-dead mouse APOBEC3 can bind to
      murine leukemia virus (MLV) reverse transcriptase. Our findings suggest that the
      mouse APOBEC3 cytidine deaminase activity is not required for retrovirus
      restriction.IMPORTANCE APOBEC3 proteins are important host cellular restriction
      factors essential for restricting retrovirus infection by causing mutations in
      the virus genome and by blocking reverse transcription. While both methods of
      restriction function in vitro, little is known about their role during in vivo
      infection. By developing transgenic mice with mutations in the cytidine
      deamination domains needed for enzymatic activity and interaction with viral RNA,
      we show that APOBEC3 proteins can still restrict in vivo infection by interacting
      with reverse transcriptase and blocking its activity. These studies demonstrate
      that APOBEC3 proteins have evolved multiple means for blocking retrovirus
      infection and that all of these means function in vivo.

PMID- 29593035
TI  - A Highly Conserved Leucine in Mammarenavirus Matrix Z Protein Is Required for Z
      Interaction with the Virus L Polymerase and Z Stability in Cells Harboring an
      Active Viral Ribonucleoprotein.
AB  - Mammarenaviruses cause chronic infections in their natural rodent hosts. Infected
      rodents shed infectious virus into excreta. Humans are infected through mucosal
      exposure to aerosols or direct contact of abraded skin with fomites, resulting in
      a wide range of manifestations from asymptomatic or mild febrile illness to
      severe life-threatening hemorrhagic fever. The mammarenavirus matrix Z protein
      has been shown to be a main driving force of virus budding and to act as a
      negative regulator of viral RNA synthesis. To gain a better understanding of how
      the Z protein exerts its several different functions, we investigated the
      interaction between Z and viral polymerase L protein using the prototypic
      mammarenavirus, lymphocytic choriomeningitis virus (LCMV). We found that in the
      presence of an active viral ribonucleoprotein (vRNP), the Z protein translocated
      from nonionic detergent-resistant, membrane-rich structures to a subcellular
      compartment with a different membrane composition susceptible to disruption by
      nonionic detergents. Alanine (A) substitution of a highly conserved leucine (L)
      at position 72 in LCMV Z protein abrogated Z-L interaction. The L72A mutation did
      not affect the stability or budding activity of Z when expressed alone, but in
      the presence of an active vRNP, mutation L72A promoted rapid degradation of Z via
      a proteasome- and lysosome-independent pathway. Accordingly, L72A mutation in the
      Z protein resulted in nonviable LCMV. Our findings have uncovered novel aspects
      of the dynamics of the Z protein for which a highly conserved L residue was
      strictly required.IMPORTANCE Several mammarenaviruses, chiefly Lassa virus
      (LASV), cause hemorrhagic fever disease in humans and pose important public
      health concerns in their regions of endemicity. Moreover, mounting evidence
      indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic
      choriomeningitis virus (LCMV), is a neglected human pathogen of clinical
      significance. The mammarenavirus matrix Z protein plays critical roles in
      different steps of the viral life cycle by interacting with viral and host
      cellular components. Here we report that alanine substitution of a highly
      conserved leucine residue, located at position 72 in LCMV Z protein, abrogated Z
      L interaction. The L72A mutation did not affect Z budding activity but promoted
      its rapid degradation in the presence of an active viral ribonucleoprotein
      (vRNP). Our findings have uncovered novel aspects of the dynamics of the Z
      protein for which a highly conserved L residue was strictly required.

PMID- 29593033
TI  - Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as
      Ligands.
AB  - Group/species C rotaviruses (RVCs) have been identified as important pathogens of
      acute gastroenteritis (AGE) in children, family-based outbreaks, as well as
      animal infections. However, little is known regarding their host-specific
      interaction, infection, and pathogenesis. In this study, we performed serial
      studies to characterize the function and structural features of a human G4P[2]
      RVC VP8* that is responsible for the host receptor interaction. Glycan
      microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood
      group antigens (HBGAs), which was confirmed by synthetic glycan-/saliva-based
      binding assays and hemagglutination of red blood cells, establishing a paradigm
      of RVC VP8*-glycan interactions. Furthermore, the high-resolution crystal
      structure of the human RVC VP8* was solved, showing a typical galectin-like
      structure consisting of two beta-sheets but with significant differences from
      cogent proteins of group A rotaviruses (RVAs). The VP8* in complex with a type A
      trisaccharide displays a novel ligand binding site that consists of a particular
      set of amino acid residues of the C-D, G-H, and K-L loops. RVC VP8* interacts
      with type A HBGAs through a unique mechanism compared with that used by RVAs. Our
      findings shed light on the host-virus interaction and the coevolution of RVCs and
      will facilitate the development of specific antivirals and vaccines.IMPORTANCE
      Group/species C rotaviruses (RVCs), members of Reoviridae family, infect both
      humans and animals, but our knowledge about the host factors that control host
      susceptibility and specificity is rudimentary. In this work, we characterized the
      glycan binding specificity and structural basis of a human RVC that recognizes
      type A HBGAs. We found that human RVC VP8*, the rotavirus host ligand binding
      domain that shares only ~15% homology with the VP8* domains of RVAs, recognizes
      type A HBGA at an as-yet-unknown glycan binding site through a mechanism distinct
      from that used by RVAs. Our new advancements provide insights into RVC-cell
      attachment, the critical step of virus infection, which will in turn help the
      development of control and prevention strategies against RVs.

PMID- 29593037
TI  - Dynein engages and disassembles cytosol-localized SV40 to promote infection.
AB  - During entry, polyomavirus (PyV) is endocytosed and sorts to the endoplasmic
      reticulum (ER) where it penetrates the ER membrane to reach the cytosol. From the
      cytosol, the virus moves to the nucleus to cause infection. How PyV is
      transported from the cytosol into the nucleus, a crucial infection step, is
      unclear. We found that upon reaching the cytosol, the archetype PyV SV40 recruits
      the cytoplasmic dynein motor, which disassembles the viral particle. This
      reaction enables the resulting disassembled virus to enter the nucleus to promote
      infection. Our findings reveal how a cytosolic motor can be hijacked to impart
      conformational changes to a viral particle, which is essential for successful
      infection.IMPORTANCE How a non-enveloped virus successfully traffics from the
      cell surface to the nucleus to cause infection remains enigmatic in many
      instances. In the case of the non-enveloped PyV, the viral particle is sorted
      from the plasma membrane to the ER and then the cytosol from where it enters the
      nucleus to promote infection. The molecular mechanism by which PyV reaches the
      nucleus from the cytosol is not entirely clear. Here we demonstrate that the
      prototype PyV SV40 recruits dynein upon reaching the cytosol. Importantly, this
      cellular motor disassembles the viral particle during cytosol-to-nuclear
      transport to cause infection.

PMID- 29593036
TI  - Variation at Extra-epitopic Amino Acid Residues Influences Suppression of
      Influenza Virus Replication by M158-66 Epitope-Specific CD8+ T Lymphocytes.
AB  - Influenza virus-specific CD8+ T lymphocytes (CTLs) contribute to clearance of
      influenza virus infections and reduce disease severity. Variation at amino acid
      residues located in or outside CTL epitopes has been shown to affect viral
      recognition by virus-specific CTLs. In the present study, we investigated the
      effect of naturally occurring variation at residues outside the conserved
      immunodominant and HLA*0201-restricted M158-66 epitope, located in the influenza
      virus M1 protein, on the extent of virus replication in the presence of CTLs
      specific for the epitope. To this end, we used isogenic viruses with an M1 gene
      segment derived from either an avian or a human influenza virus, HLA-transgenic
      human epithelial cells, human T cell clones specific for the M158-66 epitope or a
      control epitope, and a novel, purposely developed in vitro system to coculture
      influenza virus-infected cells with T cells. We found that the M gene segment of
      a human influenza A/H3N2 virus afforded the virus the capacity to replicate
      better in the presence of M158-66-specific CTLs than the M gene segment of avian
      viruses. These findings are in concordance with previously observed differential
      CTL activation, caused by variation at extra-epitopic residues, and may reflect
      an immune adaptation strategy of human influenza viruses that allows them to cope
      with potent CTL immunity to the M158-66 epitope in HLA-A*0201-positive
      individuals, resulting in increased virus replication and shedding and possibly
      increasing disease severity.IMPORTANCE Influenza viruses are among the leading
      causes of acute respiratory tract infections. CD8+ T lymphocytes display a high
      degree of cross-reactivity with influenza A viruses of various subtypes and are
      considered an important correlate of protection. Unraveling viral immune evasion
      strategies and identifying signs of immune adaptation are important for defining
      the role of CD8+ T lymphocytes in affording protection more accurately. Improving
      our insight into the interaction between influenza viruses and virus-specific
      CD8+ T lymphocyte immunity may help to advance our understanding of influenza
      virus epidemiology, aid in risk assessment of potentially pandemic influenza
      virus strains, and benefit the design of vaccines that induce more broadly
      protective immunity.

PMID- 29593038
TI  - Conformational Stability of the Hemagglutinin of H5N1 Influenza A Viruses
      Influences Susceptibility to Broadly Neutralizing Stem Antibodies.
AB  - Vaccines that elicit broadly neutralizing antibodies to the conserved stem of
      hemagglutinin (HA) are being developed as universal influenza vaccines that
      protect against influenza across multiple years. However, different influenza
      virus strains, even those in the same subtype with identical stem sequences, can
      vary in susceptibility to broadly neutralizing stem antibodies, and the reasons
      are not understood. Here we studied potential mechanisms underlying the differing
      sensitivities of a panel of H5N1 HA pseudoviruses to broadly neutralizing stem
      antibodies. We found that greater HA conformational stability, as measured by
      thermal inactivation and pH triggering of conformational changes, correlates with
      reduced neutralization sensitivity and antibody binding to HA under neutral- and
      low-pH conditions. Our data indicate that the conformational stability of HA is
      an important attribute of susceptibility to broadly neutralizing stem antibodies
      and is influenced by residues outside the stem antibody epitopes.IMPORTANCE The
      influenza virus surface glycoprotein hemagglutinin (HA) mediates virus attachment
      and membrane fusion between virus and host cells, allowing the viral core to
      enter the host cell cytoplasm for replication. Fusion occurs when HA undergoes
      low-pH-induced-conformational changes during endocytosis. Broadly neutralizing
      antibodies targeted to the conserved stem region of HA interfere with
      conformational changes required for fusion. Vaccines that elicit such antibodies
      are being developed as novel universal influenza vaccines for multiyear
      protection. We investigated why H5N1 HAs from different strains differ in their
      sensitivity to broadly neutralizing stem antibodies despite having conserved
      epitopes. We report that HA conformational stability due to residues outside the
      antibody binding site accounted for much of the variation in susceptibility to
      neutralization by stem antibodies. These findings highlight the importance of
      nonepitope residues in influencing neutralization sensitivity to stem antibodies
      and the complexities in developing universal vaccines targeting conserved
      epitopes in the HA stem.

PMID- 29593039
TI  - Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells
      following Latency Reversal Ex Vivo.
AB  - Current efforts toward human immunodeficiency virus (HIV) eradication include
      approaches to augment immune recognition and elimination of persistently infected
      cells following latency reversal. Natural killer (NK) cells, the main effectors
      of the innate immune system, recognize and clear targets using different
      mechanisms than CD8+ T cells, offering an alternative or complementary approach
      for HIV clearance strategies. We assessed the impact of interleukin 15 (IL-15)
      treatment on NK cell function and the potential for stimulated NK cells to clear
      the HIV reservoir. We measured NK cell receptor expression, antibody-dependent
      cell-mediated cytotoxicity (ADCC), cytotoxicity, interferon gamma (IFN-gamma)
      production, and antiviral activity in autologous HIV replication systems. All NK
      cell functions were uniformly improved by IL-15, and, more importantly, IL-15
      treated NK cells were able to clear latently HIV-infected cells after exposure to
      vorinostat, a clinically relevant latency-reversing agent. We also demonstrate
      that NK cells from HIV-infected individuals aviremic on antiretroviral therapy
      can be efficiently stimulated with IL-15. Our work opens a promising line of
      investigation leading to future immunotherapies to clear persistent HIV infection
      using NK cells.IMPORTANCE In the search for an HIV cure, strategies to enhance
      immune function to allow recognition and clearance of HIV-infected cells
      following latency reversal are being evaluated. Natural killer (NK) cells possess
      characteristics that can be exploited for immunotherapy against persistent HIV
      infection. We demonstrate that NK cells from HIV-positive donors can be strongly
      stimulated with IL-15, improving their antiviral and cytotoxic potential and,
      more importantly, clearing HIV-infected cells after latency reversal with a
      clinically relevant drug. Our results encourage further investigation to design
      NK cell-based immunotherapies to achieve HIV eradication.

PMID- 29593040
TI  - Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature
      Mutagenesis in the Viral Genome.
AB  - Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical
      cancer, accompanied by the accumulation of somatic mutations into the host
      genome. There are concomitant genetic changes in the HPV genome during viral
      infection; however, their relevance to cervical carcinogenesis is poorly
      understood. Here, we explored within-host genetic diversity of HPV by performing
      deep-sequencing analyses of viral whole-genome sequences in clinical specimens.
      The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR
      from total cellular DNA of cervical exfoliated cells collected from patients with
      cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and
      were deep sequenced. After constructing a reference viral genome sequence for
      each specimen, nucleotide positions showing changes with >0.5% frequencies
      compared to the reference sequence were determined for individual samples. In
      total, 1,052 positions of nucleotide variations were detected in HPV genomes from
      151 samples (CIN1, n = 56; CIN2/3, n = 68; ICC, n = 27), with various numbers per
      sample. Overall, C-to-T and C-to-A substitutions were the dominant changes
      observed across all histological grades. While C-to-T transitions were
      predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell
      below that of C-to-A transversions in ICC. Analysis of the trinucleotide context
      encompassing substituted bases revealed that TpCpN, a preferred target sequence
      for cellular APOBEC cytosine deaminases, was a primary site for C-to-T
      substitutions in the HPV genome. These results strongly imply that the APOBEC
      proteins are drivers of HPV genome mutation, particularly in CIN1
      lesions.IMPORTANCE HPVs exhibit surprisingly high levels of genetic diversity,
      including a large repertoire of minor genomic variants in each viral genotype.
      Here, by conducting deep-sequencing analyses, we show for the first time a
      comprehensive snapshot of the within-host genetic diversity of high-risk HPVs
      during cervical carcinogenesis. Quasispecies harboring minor nucleotide
      variations in viral whole-genome sequences were extensively observed across
      different grades of CIN and cervical cancer. Among the within-host variations, C
      to-T transitions, a characteristic change mediated by cellular APOBEC cytosine
      deaminases, were predominantly detected throughout the whole viral genome, most
      strikingly in low-grade CIN lesions. The results strongly suggest that within
      host variations of the HPV genome are primarily generated through the interaction
      with host cell DNA-editing enzymes and that such within-host variability is an
      evolutionary source of the genetic diversity of HPVs.

PMID- 29593041
TI  - Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse
      Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against
      DENV-2 and -4.
AB  - Recent data obtained with the live-attenuated tetravalent dengue CYD-TDV vaccine
      showed higher protective efficacy against dengue virus type 4 (DENV-4) than
      against DENV-2. In contrast, results from previous studies in nonhuman primates
      predicted comparable high levels of protection against each serotype. Maximum
      viral loads achieved in macaques by subcutaneous inoculation of DENV are
      generally much lower than those observed in naturally dengue virus-infected
      humans. This may contribute to an overestimation of vaccine efficacy. Using more
      stringent DENV infection conditions consisting of the intravenous inoculation of
      107 50% cell culture infectious doses (CCID50) in CYD-TDV-vaccinated macaques,
      complete protection (i.e., undetectable viral RNA) was achieved in all 6 monkeys
      challenged with DENV-4 and in 6/18 of those challenged with DENV-2, including
      transiently positive animals. All other infected macaques (12/18) developed
      sustained DENV-2 RNAemia (defined as detection of viral RNA in serum samples)
      although 1 to 3 log10 units below the levels achieved in control animals. Similar
      results were obtained with macaques immunized with either CYD-TDV or monovalent
      (MV) CYD-2. This suggests that partial protection against DENV-2 was mediated
      mainly by CYD-2 and not by the other CYDs. Postchallenge induction of strong
      anamnestic responses, suggesting efficient vaccine priming, likely contributed to
      the reduction of DENV-2 RNAemia. Finally, an inverse correlation between DENV RNA
      titers postchallenge and vaccine-induced homotypic neutralizing antibody titers
      prechallenge was found, emphasizing the key role of these antibodies in
      controlling DENV infection. Collectively, these data show better agreement with
      reported data on CYD-TDV clinical vaccine efficacy against DENV-2 and DENV-4.
      Despite inherent limitations of the nonhuman primate model, these results
      reinforce its value in assessing the efficacy of dengue vaccines.IMPORTANCE The
      nonhuman primate (NHP) model is the most widely recognized tool for assessing the
      protective activity of dengue vaccine candidates, based on the prevention of
      postinfection DENV viremia. However, its use has been questioned after the recent
      CYD vaccine phase III trials, in which moderate protective efficacy against DENV
      2 was reported, despite full protection against DENV-2 viremia previously being
      demonstrated in CYD-vaccinated monkeys. Using a reverse translational approach,
      we show here that the NHP model can be improved to achieve DENV-2 protection
      levels that show better agreement with clinical efficacy. With this new model, we
      demonstrate that the injection of the CYD-2 component of the vaccine, in either a
      monovalent or a tetravalent formulation, is able to reduce DENV-2 viremia in all
      immunized animals, and we provide clear statistical evidence that DENV-2
      neutralizing antibodies are able to reduce viremia in a dose-dependent manner.

PMID- 29593042
TI  - Varicella-Zoster Virus ORF63 Protects Human Neuronal and Keratinocyte Cell Lines
      from Apoptosis and Changes Its Localization upon Apoptosis Induction.
AB  - There are many facets of varicella-zoster virus (VZV) pathogenesis that are not
      fully understood, such as the mechanisms involved in the establishment of
      lifelong latency, reactivation, and development of serious conditions like
      postherpetic neuralgia (PHN). Virus-encoded modulation of apoptosis has been
      suggested to play an important role in these processes. VZV open reading frame 63
      (ORF63) has been shown to modulate apoptosis in a cell-type-specific manner, but
      the impact of ORF63 on cell death pathways has not been examined in isolation in
      the context of human cells. We sought to elucidate the effect of VZV ORF63 on
      apoptosis induction in human neuron and keratinocyte cell lines. VZV ORF63 was
      shown to protect differentiated SH-SY5Y neuronal cells against staurosporine
      induced apoptosis. In addition, VZV infection did not induce high levels of
      apoptosis in the HaCaT human keratinocyte line, highlighting a delay in apoptosis
      induction. VZV ORF63 was shown to protect HaCaT cells against both staurosporine-
      and Fas ligand-induced apoptosis. Confocal microscopy was utilized to examine VZV
      ORF63 localization during apoptosis induction. In VZV infection and ORF63
      expression alone, VZV ORF63 became more cytoplasmic, with aggregate formation
      during apoptosis induction. Taken together, this suggests that VZV ORF63 protects
      both differentiated SH-SY5Y cells and HaCaT cells from apoptosis induction and
      may mediate this effect through its localization change during apoptosis. VZV
      ORF63 is a prominent VZV gene product in both productive and latent infection and
      thus may play a critical role in VZV pathogenesis by aiding neuron and
      keratinocyte survival.IMPORTANCE VZV, a human-specific alphaherpesvirus, causes
      chicken pox during primary infection and establishes lifelong latency in the
      dorsal root ganglia (DRG). Reactivation of VZV causes shingles, which is often
      followed by a prolonged pain syndrome called postherpetic neuralgia. It has been
      suggested that the ability of the virus to modulate cell death pathways is linked
      to its ability to establish latency and reactivate. The significance of our
      research lies in investigating the ability of ORF63, a VZV gene product, to
      inhibit apoptosis in novel cell types crucial for VZV pathogenesis. This will
      allow an increased understanding of critical enigmatic components of VZV
      pathogenesis.

PMID- 29593043
TI  - A Vaccine Platform against Arenaviruses Based on a Recombinant Hyperattenuated
      Mopeia Virus Expressing Heterologous Glycoproteins.
AB  - Several Old World and New World arenaviruses are responsible for severe endemic
      and epidemic hemorrhagic fevers, whereas other members of the Arenaviridae family
      are nonpathogenic. To date, no approved vaccines, antivirals, or specific
      treatments are available, except for Junin virus. However, protection of nonhuman
      primates against Lassa fever virus (LASV) is possible through the inoculation of
      the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with
      LASV. We reasoned that this virus, modified by using reverse genetics, would
      represent the basis for the generation of a vaccine platform against LASV and
      other pathogenic arenaviruses. After showing evidence of exoribonuclease (ExoN)
      activity in NP of MOPV, we found that this activity was essential for
      multiplication in antigen-presenting cells. The introduction of multiple
      mutations in the ExoN site of MOPV NP generated a hyperattenuated strain
      (MOPVExoN6b) that is (i) genetically stable over passages, (ii) has increased
      immunogenic properties compared to those of MOPV, and (iii) still promotes a
      strong type I interferon (IFN) response. MOPVExoN6b was further modified to
      harbor the envelope glycoproteins of heterologous pathogenic arenaviruses, such
      as LASV or Lujo, Machupo, Guanarito, Chapare, or Sabia virus in order to broaden
      specific antigenicity while preserving the hyperattenuated characteristics of the
      parental strain. Our MOPV-based vaccine candidate for LASV, MOPEVACLASV, was used
      in a one-shot immunization assay in nonhuman primates and fully protected them
      from a lethal challenge with LASV. Thus, our hyperattenuated strain of MOPV
      constitutes a promising new live-attenuated vaccine platform to immunize against
      several, if not all, pathogenic arenaviruses.IMPORTANCE Arenaviruses are emerging
      pathogens transmitted to humans by rodents and responsible for endemic and
      epidemic hemorrhagic fevers of global concern. Nonspecific symptoms associated
      with the onset of infection make these viruses difficult to distinguish from
      other endemic pathogens. Moreover, the unavailability of rapid diagnosis in the
      field delays the identification of the virus and early care for treatment and
      favors spreading. The vaccination of exposed populations would be of great help
      to decrease morbidity and human-to-human transmission. Using reverse genetics, we
      generated a vaccine platform for pathogenic arenaviruses based on a modified and
      hyperattenuated strain of the nonpathogenic Mopeia virus and showed that the
      Lassa virus candidate fully protected nonhuman primates from a lethal challenge.
      These results showed that a rationally designed recombinant MOPV-based vaccine is
      safe, immunogenic, and efficacious in nonhuman primates.

PMID- 29593044
TI  - Control of HIV-1 Pathogenesis in Viremic Nonprogressors Is Independent of Gag
      Specific Cytotoxic T Lymphocyte Responses.
AB  - Viremic nonprogressors (VNPs) constitute a very scarce group of untreated human
      immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain stable
      CD4+ T cell counts despite high levels of HIV-1 replication. The specific factors
      associated with this atypical control of the HIV infection have been poorly
      described. Since specific T cell responses seem to be one of the main causes of
      HIV-1 control in elite controllers, we studied whether HIV-1 Gag-specific
      cytotoxic T lymphocyte (CTL) responses could also modulate disease control in
      VNPs. We characterized the immune responses from four VNPs compared to those of
      five standard progressors (SPs) during the first years of HIV-1 infection. We
      observed no differences in the breadth and frequency of Gag-specific cellular
      responses. Furthermore, we obtained 217 HIV-1Gag clonal sequences in which the
      viral variability of Gag increased over 3 years of infection for synonymous and
      nonsynonymous mutations in both VNPs and SPs. VNPs evolution rates in gag were
      comparable to SPs. This observation is in line with a similar accumulation of CTL
      putative escape mutations in Gag epitopes targeted by CTL responses. Altogether,
      the absence of viral pathogenesis in VNP individuals seems to be independent of
      HIV-Gag-specific CTL responses. This novel information guides to the study of
      alternative mechanism of HIV-1 pathogenesis control.IMPORTANCE Control of HIV
      infection has been widely studied in elite controllers or long-term nonprogressor
      models. However, there is a less-known group of individuals, termed viremic
      nonprogressors (VNPs), who maintain stable CD4+ T cell counts despite high plasma
      viremia. The mechanisms involved in this remarkable control of HIV-1 pathogenesis
      clearly have implications for the development of new drugs and vaccines. We show
      here for the first time that VNPs have immune responses and HIV-gag evolution
      similar to those of standard progressors. Remarkably, we demonstrate that the
      mechanism of pathogenesis control in these individuals differs from some elite
      controllers that are reported to have improved immune control. This is noteworthy
      since it opens the door to new, as-yet-unknown mechanisms for HIV control. Our
      novel results advance the understanding of mechanisms involved in viremic
      nonprogression and suggest that there are alternative mechanisms to the adaptive
      immune responses for an effective control of viral pathogenesis.

PMID- 29593045
TI  - Degradation of a novel DNA damage response protein, tankyrase 1 binding protein 1
      (Tab182), following adenovirus infection.
AB  - Infection by most DNA viruses activates a cellular DNA damage response (DDR),
      which may be to the detriment or advantage of the virus. In the case of
      adenoviruses, they neutralise anti-viral effects of DDR activation by targeting a
      number of proteins for rapid proteasome-mediated degradation. We have now
      identified a novel DDR protein, tankyrase 1 binding protein 1 (TNKS1BP1 also
      known as Tab182), which is degraded during infection by adenovirus 5 and
      adenovirus 12. In both cases, degradation requires the action of E1B55K and
      E4orf6 viral proteins and is mediated through the proteasome by the action of
      cullin-based cellular E3 ligases. The degradation of Tab182 appears to be
      serotype specific as the protein remains relatively stable following infection
      with adenoviruses 4, 7, 9 and 11. We have gone on to confirm that Tab182 is an
      integral component of the CNOT complex, which has transcriptional regulatory,
      deadenylation and E3 ligase activity. At least 2 other members of the complex
      (CNOT3 and CNOT7) are also reduced in level during adenovirus infection whereas
      levels of CNOT4 and CNOT1 remain stable. Depletion of Tab182 with siRNA enhances
      expression of E1As to a limited extent during adenovirus infection but depletion
      of CNOT1 is particularly advantageous to the virus and results in a marked
      increase in expression of adenovirus early proteins. In addition, depletion of
      Tab182 and CNOT1 results in a limited increase in viral DNA during infection. We
      conclude that the cellular CNOT complex is a previously unidentified major target
      for adenoviruses during infection.ImportanceAdenoviruses target a number of
      cellular proteins involved in the DNA damage response for rapid degradation. We
      have now shown that Tab182, which we have confirmed to be an integral component
      of the mammalian CNOT complex, is degraded following infection by adenovirus
      serotypes 5 and 12. This requires the viral E1B55K and E4orf6 proteins and is
      mediated by cullin-based E3 ligases and the proteasome. In addition to Tab182,
      other CNOT proteins are also reduced during adenovirus infection. Thus, CNOT3 and
      CNOT7, for example, are degraded whereas CNOT4 and CNOT1 are not. siRNA-mediated
      depletion of components of the complex enhances the expression of adenovirus
      early proteins and increases the concentration of viral DNA produced during
      infection. This study highlights a novel protein complex, CNOT, which is targeted
      for adenovirus-mediated protein degradation. To our knowledge this is the first
      time that the CNOT complex has been identified as an adenoviral target.

PMID- 29593046
TI  - Host Factor SPCS1 Regulates the Replication of Japanese Encephalitis Virus
      through Interactions with Transmembrane Domains of NS2B.
AB  - Signal peptidase complex subunit 1 (SPCS1) is a newly identified host factor that
      regulates flavivirus replication, but the molecular mechanism is not fully
      understood. Here, using Japanese encephalitis virus (JEV) as a model, we
      investigated the mechanism through which the host factor SPCS1 regulates the
      replication of flaviviruses. We first validated the regulatory function of SPCS1
      in JEV propagation by knocking down and knocking out endogenous SPCS1. The loss
      of SPCS1 function markedly reduced intracellular virion assembly and the
      production of infectious JEV particles but did not affect cell entry, RNA
      replication, or translation of the virus. SPCS1 was found to interact with
      nonstructural protein 2B (NS2B), which is involved in posttranslational protein
      processing and virus assembly. Serial deletion mutation of the JEV NS2B protein
      revealed that two transmembrane domains, NS2B(1-49) and NS2B(84-131), interact
      with SPCS1. Further mutagenesis analysis of conserved flavivirus residues in two
      SPCS1 interaction domains of NS2B demonstrated that G12A, G37A, and G47A in
      NS2B(1-49) and P112A in NS2B(84-131) weakened the interaction with SPCS1.
      Deletion mutation of SPCS1 revealed that SPCS1(91-169), which contains two
      transmembrane domains, was involved in interactions with both NS2B(1-49) and
      NS2B(84-131). Taken together, these results demonstrate that SPCS1 affects viral
      replication by interacting with NS2B, thereby influencing the posttranslational
      processing of JEV proteins and the assembly of virions.IMPORTANCE Understanding
      virus-host interactions is important for elucidating the molecular mechanisms of
      virus propagation and identifying potential antiviral targets. Previous reports
      demonstrated that SPCS1 is involved in the flavivirus life cycle, but the
      mechanism remains unknown. In this study, we confirmed that SPCS1 participates in
      the posttranslational protein processing and viral assembly stages of the JEV
      life cycle but not in the cell entry, genome RNA replication, or translation
      stages. Furthermore, we found that SPCS1 interacts with two independent
      transmembrane domains of the flavivirus NS2B protein. NS2B also interacts with
      NS2A, which is proposed to mediate virus assembly. Therefore, we propose a
      protein-protein interaction model showing how SPCS1 participates in the assembly
      of JEV particles. These findings expand our understanding of how host factors
      participate in the flavivirus replication life cycle and identify potential
      antiviral targets for combating flavivirus infection.

PMID- 29593047
TI  - Interleukin-27R Signaling Mediates Early Viral Containment and Impacts Innate and
      Adaptive Immunity after Chronic Lymphocytic Choriomeningitis Virus Infection.
AB  - Chronic viral infections represent a major challenge to the host immune response,
      and a unique network of immunological elements, including cytokines, are required
      for their containment. By using a model persistent infection with the natural
      murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we
      investigated the role of one such cytokine, interleukin-27 (IL-27), in the
      control of chronic infection. We found that IL-27 receptor (IL-27R) signaling
      promoted control of LCMV Cl13 as early as days 1 and 5 after infection and that
      il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells
      (DCs) and myeloid cells. In particular, plasmacytoid DCs (pDCs), the most potent
      type 1 interferon (IFN-I)-producing cells, significantly increased il27p28 in a
      Toll-like receptor 7 (TLR7)-dependent fashion. Notably, mice deficient in an IL
      27-specific receptor, WSX-1, exhibited a pleiotropy of innate and adaptive immune
      alterations after chronic lymphocytic choriomeningitis virus (LCMV) infection,
      including compromised NK cell cytotoxicity and antibody responses. While, the
      majority of these immune alterations appeared to be cell extrinsic, cell
      intrinsic IL-27R was necessary to maintain early pDC numbers, which, alongside
      lower IFN-I transcription in CD11b+ DCs and myeloid cells, may explain the
      compromised IFN-I elevation that we observed early after LCMV Cl13 infection in
      IL-27R-deficient mice. Together, these data highlight the critical role of IL-27
      in enabling optimal antiviral immunity early and late after infection with a
      systemic persistent virus and suggest that a previously unrecognized positive
      feedback loop mediated by IL-27 in pDCs might be involved in this
      process.IMPORTANCE Persistently replicating pathogens, such as human
      immunodeficiency virus, hepatitis B virus, and hepatitis C virus, represent major
      health problems worldwide. These infections impose a long-term challenge on the
      host immune system, which must be heavily and continuously regulated to keep
      pathogen replication in check without causing fatal immunopathology. Using a
      persistently replicating rodent pathogen, LCMV, in its natural host, we
      identified the cellular sources and effects of one important regulatory pathway,
      interleukin-27 receptor WSX-1 signaling, that is required for both very early and
      late restriction of chronic (but not acute) infection. We found that WSX-1 was
      necessary to promote innate immunity and the development of aberrant adaptive
      immune responses. This not only highlights the role of IL-27 receptor signaling
      in regulating distinct host responses that are known to be necessary to control
      chronic infections, but also positions IL-27 as a potential therapeutic target
      for their modulation.

PMID- 29593048
TI  - Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated
      HIV DNA.
AB  - Analytic treatment interruption (ATI) studies are required to evaluate strategies
      aimed at achieving ART-free HIV remission, but the impact of ATI on the viral
      reservoir remains unclear. We validated a DNA size selection-based assay for
      measuring levels of integrated HIV DNA and applied it to assess the effects of
      short-term ATI on the HIV reservoir. Samples from participants from four AIDS
      Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels.
      Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12
      participants with available samples pre-ATI and approximately 6 months after ART
      resumption. Four participants also had samples available during the ATI. The
      median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size
      exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV
      DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated
      99% of unintegrated HIV DNA species and strongly correlated with the established
      Alu-gag assay. For the majority of individuals, integrated DNA levels increased
      during ATI and subsequently declined upon ART resumption. There was no
      significant difference in the levels of integrated HIV DNA between the pre- and
      post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of
      0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels
      of integrated HIV DNA in participants who underwent an ATI, followed by 6 months
      of ART. This suggests that short-term ATI can be conducted without a significant
      impact on the levels of integrated proviral DNA in the peripheral
      blood.IMPORTANCE Interventions aimed at achieving sustained antiretroviral
      therapy (ART)-free HIV remission require treatment interruption trials to assess
      their efficacy. However, these trials are accompanied by safety concerns related
      to the expansion of the viral reservoir. We validated an assay that uses an
      automated DNA size-selection platform for quantifying levels of integrated HIV
      DNA and is less sample- and labor-intensive than current assays. Using stored
      samples from AIDS Clinical Trials Group studies, we found that short-term ART
      discontinuation had minimal impact on integrated HIV DNA levels after ART
      resumption, providing reassurance about the reservoir effects of short-term
      treatment interruption trials.

PMID- 29593049
TI  - Mosquito Saliva Reshapes Alphavirus Infection and Immunopathogenesis.
AB  - Alphaviruses are transmitted to humans via bites of infected mosquitoes. Although
      alphaviruses have caused a wide range of outbreaks and crippling disease, the
      availability of licensed vaccines or antiviral therapies remains limited.
      Mosquito vectors such as Aedes and Culex are the main culprits in the
      transmission of alphaviruses. This review explores how mosquito saliva may
      promote alphavirus infection. Identifying the roles of mosquito-derived factors
      in alphavirus pathogenesis will generate novel tools to circumvent and control
      mosquito-borne alphavirus infections in humans.

PMID- 29593051
TI  - Adaptation to Noise in Human Speech Recognition Unrelated to the Medial
      Olivocochlear Reflex.
AB  - Sensory systems constantly adapt their responses to the current environment. In
      hearing, adaptation may facilitate communication in noisy settings, a benefit
      frequently (but controversially) attributed to the medial olivocochlear reflex
      (MOCR) enhancing the neural representation of speech. Here, we show that human
      listeners (N = 14; five male) recognize more words presented monaurally in
      ipsilateral, contralateral, and bilateral noise when they are given some time to
      adapt to the noise. This finding challenges models and theories that claim that
      speech intelligibility in noise is invariant over time. In addition, we show that
      this adaptation to the noise occurs also for words processed to maintain the slow
      amplitude modulations in speech (the envelope) disregarding the faster
      fluctuations (the temporal fine structure). This demonstrates that noise
      adaptation reflects an enhancement of amplitude modulation speech cues and is
      unaffected by temporal fine structure cues. Last, we show that cochlear implant
      users (N = 7; four male) show normal monaural adaptation to ipsilateral noise.
      Because the electrical stimulation delivered by cochlear implants is independent
      from the MOCR, this demonstrates that noise adaptation does not require the MOCR.
      We argue that noise adaptation probably reflects adaptation of the dynamic range
      of auditory neurons to the noise level statistics.SIGNIFICANCE STATEMENT People
      find it easier to understand speech in noisy environments when they are given
      some time to adapt to the noise. This benefit is frequently but controversially
      attributed to the medial olivocochlear efferent reflex enhancing the
      representation of speech cues in the auditory nerve. Here, we show that the
      adaptation to noise reflects an enhancement of the slow fluctuations in amplitude
      over time that are present in speech. In addition, we show that adaptation to
      noise for cochlear implant users is not statistically different from that for
      listeners with normal hearing. Because the electrical stimulation delivered by
      cochlear implants is independent from the medial olivocochlear efferent reflex,
      this demonstrates that adaptation to noise does not require this reflex.

PMID- 29593050
TI  - eCD4-Ig Variants That More Potently Neutralize HIV-1.
AB  - The human immunodeficiency virus type 1 (HIV-1) entry inhibitor eCD4-Ig is a
      fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more
      potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1
      broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig
      neutralized all HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates
      that it has been tested against, suggesting that it may be useful in clinical
      settings, where antibody escape is a concern. Here, we characterize three new
      eCD4-Ig variants, each with a different architecture and each utilizing D1.22, a
      stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent
      than our original eCD4-Ig variant, with a construct bearing four D1.22 domains
      (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated
      less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than
      eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant
      (eD1.22-Ig). A variant with the same architecture as the original eCD4-Ig (eD1.22
      D2-Ig) showed modestly higher thermal stability and best prevented the promotion
      of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4
      Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein
      gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations
      contributed to the potency of eD1.22-D2-Ig and that introduction of these changes
      into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold
      more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig
      variants with properties optimized for prophylaxis, therapy, and cure
      applications.IMPORTANCE HIV-1 bNAbs have properties different from those of
      antiretroviral compounds. Specifically, antibodies can enlist immune effector
      cells to eliminate infected cells, whereas antiretroviral compounds simply
      interfere with various steps in the viral life cycle. Unfortunately, HIV-1 is
      adept at evading antibody recognition, limiting the utility of antibodies as a
      treatment for HIV-1 infection or as part of an effort to eradicate latently
      infected cells. eCD4-Ig is an antibody-like entry inhibitor that closely mimics
      HIV-1's obligate receptors. eCD4-Ig appears to be qualitatively different from
      antibodies, since it neutralizes all HIV-1, HIV-2, and SIV isolates. Here, we
      characterize three new structurally distinct eCD4-Ig variants and show that each
      excels in a key property useful to prevent, treat, or cure an HIV-1 infection.
      For example, one variant neutralized HIV-1 most efficiently, while others best
      enlisted natural killer cells to eliminate infected cells. These observations
      will help generate eCD4-Ig variants optimized for different clinical
      applications.

PMID- 29593052
TI  - Long-Term Depression Is Independent of GluN2 Subunit Composition.
AB  - NMDA receptors (NMDARs) mediate both long-term potentiation and long-term
      depression (LTD) and understanding how a single receptor can initiate both
      phenomena remains a major question in neuroscience. A prominent hypothesis
      implicates the NMDAR subunit composition, specifically GluN2A and GluN2B, in
      dictating the rules of synaptic plasticity. However, studies testing this
      hypothesis have yielded inconsistent and often contradictory results, especially
      for LTD. These inconsistent results may be due to challenges in the
      interpretation of subunit-selective pharmacology and in dissecting out the
      contributions of differential channel properties versus the interacting proteins
      unique to GluN2A or GluN2B. In this study, we address the pharmacological and
      biochemical challenges by using a single-neuron genetic approach to delete NMDAR
      subunits in conditional knock-out mice. In addition, the recently discovered non
      ionotropic nature of NMDAR-dependent LTD allowed the rigorous assessment of
      unique subunit contributions to NMDAR-dependent LTD while eliminating the
      variable of differential charge transfer. Here we find that neither the GluN2A
      nor the GluN2B subunit is strictly necessary for either non-ionotropic or
      ionotropic LTD.SIGNIFICANCE STATEMENT NMDA receptors are key regulators of
      bidirectional synaptic plasticity. Understanding the mechanisms regulating
      bidirectional plasticity will guide development of therapeutic strategies to
      treat the dysfunctional synaptic plasticity in multiple neuropsychiatric
      disorders. Because of the unique properties of the NMDA receptor GluN2 subunits,
      they have been postulated to differentially affect synaptic plasticity. However,
      there has been significant controversy regarding the roles of the GluN2 subunits
      in synaptic long term depression (LTD). Using single-neuron knock-out of the
      GluN2 subunits, we show that LTD requires neither GluN2A nor GluN2B.

PMID- 29593053
TI  - Functional Organization of the Temporal-Parietal Junction for Theory of Mind in
      Preverbal Infants: A Near-Infrared Spectroscopy Study.
AB  - Successful human social life requires imagining what others believe or think to
      understand and predict behavior. This ability, often referred to as theory of
      mind (ToM), reliably engages a specialized network of temporal and prefrontal
      brain regions in older children and adults, including selective recruitment of
      the temporal-parietal junction (TPJ). To date, how and when this specialized
      brain organization for ToM arises is unknown due to limitations in functional
      neuroimaging at younger ages. Here, we used the emerging technique of functional
      near-infrared spectroscopy to measure the functional brain response across
      parietal, temporal, and prefrontal regions in 7-month-old male and female infants
      as they viewed different video scenarios of a person searching for a hidden
      object. Over different conditions, we manipulated whether the person held an
      accurate (true) or inaccurate (false) belief about the location of the hidden
      object in the videos. In two separate experiments, we observed that activity from
      the TPJ, but not other temporal and prefrontal regions, spontaneously tracked
      with the beliefs of the other person, responding more during scenarios when the
      other person's belief regarding the location of the object was false compared
      with scenarios when her belief was true. These results mirror those obtained with
      adults to show that the TPJ already shows some functional organization relevant
      to high-level social cognition by around 7 months of age. Furthermore, these
      results suggest that infants may draw on similar core mechanisms to implicitly
      track beliefs, as adults do when reasoning explicitly about them.SIGNIFICANCE
      STATEMENT Humans selectively engage a network of brain regions, including the
      temporal-parietal junction (TPJ), to track what others think, an ability referred
      to as theory of mind. How and when this specialized brain organization for high
      level social cognition arises is unknown. Using the emerging technique of near
      infrared spectroscopy with 7-month-old infants, we observed that activity of the
      TPJ, but not other temporal and frontal regions, distinguished between scenarios
      when another person's belief about the location of the object was false compared
      with scenarios when the belief was true. These results suggest that a basic
      neural architecture to understand and predict the actions of others based on
      their beliefs may be present from the first year of life.

PMID- 29593054
TI  - Low-Dimensional and Monotonic Preparatory Activity in Mouse Anterior Lateral
      Motor Cortex.
AB  - Neurons in multiple brain regions fire trains of action potentials anticipating
      specific movements, but this "preparatory activity" has not been systematically
      compared across behavioral tasks. We compared preparatory activity in auditory
      and tactile delayed-response tasks in male mice. Skilled, directional licking was
      the motor output. The anterior lateral motor cortex (ALM) is necessary for motor
      planning in both tasks. Multiple features of ALM preparatory activity during the
      delay epoch were similar across tasks. First, most neurons showed direction
      selective activity and spatially intermingled neurons were selective for either
      movement direction. Second, many cells showed mixed coding of sensory stimulus
      and licking direction, with a bias toward licking direction. Third, delay
      activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar
      direction selectivity showed high spike-count correlations. Our study forms the
      foundation to analyze the neural circuit mechanisms underlying preparatory
      activity in a genetically tractable model organism.SIGNIFICANCE STATEMENT Short
      term memories link events separated in time. Neurons in the frontal cortex fire
      trains of action potentials anticipating specific movements, often seconds before
      the movement. This "preparatory activity" has been observed in multiple brain
      regions, but has rarely been compared systematically across behavioral tasks in
      the same brain region. To identify common features of preparatory activity, we
      developed and compared preparatory activity in auditory and tactile delayed
      response tasks in mice. The same cortical area is necessary for both tasks.
      Multiple features of preparatory activity, measured with high-density silicon
      probes, were similar across tasks. We find that preparatory activity is low
      dimensional and monotonic. Our study forms a foundation for analyzing the circuit
      mechanisms underlying preparatory activity in a genetically tractable model
      organism.

PMID- 29593055
TI  - Validation of the FluoroType MTBDR Assay for Detection of Rifampin and Isoniazid
      Resistance in Mycobacterium tuberculosis Complex Isolates.
AB  - For Mycobacterium tuberculosis complex (MTBC), the rapid and accurate diagnosis
      of drug resistance is crucial to ensure early initiation of appropriate therapy.
      Recently, a new molecular diagnostic test, the FluoroType MTBDR, aimed at
      detecting rifampin and isoniazid resistance has become available. This study
      aimed to evaluate the FluoroType MTBDR in comparison to phenotypic drug
      susceptibility testing (DST) using M. tuberculosis complex isolates. MTBC
      isolates underwent phenotypic DST and were tested using the FluoroType MTBDR and
      Genotype MTBDRplus. Sanger sequencing of the key regions of rpoB, katG, inhA, and
      aphC was performed for isolates with discordant phenotypic and molecular results.
      Furthermore, isolates with specific wild-type bands missing in the Genotype
      MTBDRplus, indicating the presence of a mutation, were investigated by Sanger
      sequencing. Specificity and sensitivity, defined as the proportions of isolates
      correctly determined as susceptible and resistant by the FluoroType MTBDR
      compared to phenotypic DST, were calculated. A total of 180 culture isolates were
      included; phenotypic DST showed 85 isolates susceptible to isoniazid and
      rifampin, 7 with isoniazid monoresistance, 7 with rifampin monoresistance, and 81
      with multidrug resistance. The specificity of the FluoroType MTBDR was 100% (95%
      confidence interval [CI], 96.0 to 100%) for both rifampin and isoniazid. The
      sensitivity was 91.7% (95% CI, 83.6 to 96.6%) for isoniazid and 98.9% (95% CI,
      93.8 to 100.0%) for rifampin. The FluoroType MTBDR has a high sensitivity and
      specificity for the detection of rifampin and isoniazid resistance when using
      culture isolates.

PMID- 29593056
TI  - Biographical Feature: Mary Jane Ferraro, Ph.D., M.P.H.

PMID- 29593057
TI  - Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of
      Viruses and Bacteria in Nasopharyngeal Swab Samples.
AB  - The FilmArray Respiratory Panel 2 (RP2) is a multiplex in vitro diagnostic test
      for the simultaneous and rapid (~45-min) detection of 22 pathogens directly from
      nasopharyngeal swab (NPS) samples. It contains updated (and in some instances
      redesigned) assays that improve upon the FilmArray Respiratory Panel (RP; version
      1.7), with a faster run time. The organisms identified are adenovirus,
      coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human
      metapneumovirus, human rhinovirus/enterovirus, influenza virus A, influenza virus
      A H1, influenza virus A H1-2009, influenza virus A H3, influenza virus B,
      parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3,
      parainfluenza virus 4, respiratory syncytial virus, Bordetella pertussis,
      Chlamydia pneumoniae, and Mycoplasma pneumoniae Two new targets are included in
      the FilmArray RP2: Middle East respiratory syndrome coronavirus and Bordetella
      parapertussis This study provides data from a multicenter evaluation of 1,612
      prospectively collected NPS samples, with performance compared to that of the
      FilmArray RP or PCR and sequencing. The overall percent agreement between the
      FilmArray RP2 and the comparator testing was 99.2%. The RP2 demonstrated a
      positive percent agreement of 91.7% or greater for detection of all but three
      analytes: coronavirus OC43, B. parapertussis, and B. pertussis The FilmArray RP2
      also demonstrated a negative percent agreement of >=93.8% for all analytes. Of
      note, the adenovirus assay detects all genotypes, with a demonstrated increase in
      sensitivity. The FilmArray RP2 represents a significant improvement over the
      FilmArray RP, with a substantially shorter run time that could aid in the
      diagnosis of respiratory infections in a variety of clinical scenarios.

PMID- 29593058
TI  - Escherichia coli H-Genotyping PCR: a Complete and Practical Platform for
      Molecular H Typing.
AB  - In Escherichia coli, more than 180 O groups and 53 H types have been recognized.
      The O:H serotyping of E. coli strains is an effective method for identifying
      strains with pathogenic potential and classifying them into clonal groups. In
      particular, the serotyping of Shiga toxin-producing E. coli (STEC) strains
      provides valuable information to evaluate the routes, sources, and prevalence of
      agents in outbreak investigations and surveillance. Here, we present a complete
      and practical PCR-based H-typing system, E. coli H-genotyping PCR, consisting of
      10 multiplex PCR kits with 51 single PCR primer pairs. Primers were designed
      based on a detailed comparative analysis of sequences from all H-antigen
      (flagellin)-encoding genes, fliC and its homologs. The specificity of this system
      was confirmed by using all H type reference strains. Additionally, 362 serotyped
      wild strains were also used to evaluate its practicality. All 277 H-type
      identified isolates gave PCR products that corresponded to the results of
      serological H typing. Moreover, 76 nonmotile and nine untypeable strains could be
      successfully subtyped into any H type by the PCR system. The E. coli H-genotyping
      PCR developed here allows broader, rapid, and low-cost subtyping of H types and
      will assist epidemiological studies as well as surveillance of pathogenic E.
      coli.

PMID- 29593059
TI  - Quantitative Inference of Commutability for Clinical Viral Load Testing.

PMID- 29593061
TI  - Biomarkers of chondrosarcoma.
AB  - Clinical outcome prediction is major concern to patients with cancer. Various
      molecular markers in various carcinomas have been identified in the past few
      decades. However, accurate predictors in chondrosarcoma have not been developed,
      even though chondrosarcoma is the second most common primary bone tumour.
      Chondrosarcoma is the cartilage-forming malignancy and shows a wide spectrum of
      clinicopathological behaviours. The majority of chondrosarcoma grows slowly and
      rarely metastasises, and adequate surgery leads to a good prognosis. However,
      wide surgical excision is acquired in high-grade chondrosarcoma, because this
      tumour is highly resistant to chemotherapy and radiotherapy. To decide best
      therapy, accurate diagnostic markers are also necessary in chondrosarcoma. It is
      reported that angiogenesis and lymphangiogenesis increase by chondrosarcoma
      staging, and they are promoted by leptin and adiponectin. Several microRNAs to
      regulate vascular endothelial growth factor (VEGF)-A and VEGF-C are also
      reported. Alpha-methylacyl-CoA racemase and periostin are proposed as new
      biomarkers for differential diagnosis of enchondroma and chondrosarcoma. This
      review summarises that chondrosarcoma diagnostic markers are currently reported.

PMID- 29593062
TI  - Novel selective medium for the isolation of corynebacterium kroppenstedtii from
      heavily colonised clinical specimens.
AB  - AIMS: Granulomatous mastitis due to Corynebacterium kroppenstedtii is an
      increasingly recognised cause of an indolent and distressing mastitis in non
      lactating females. This slow-growing lipophilic organism is not reliably isolated
      using routine culture methods. A novel selective culture medium (CKSM) is
      designed to optimise the isolation of this organism from clinical specimens.
      METHODS: CKSM contains 10% galactose and Tween 80 (10%) to enhance the growth of
      C. kroppenstedtii, fosfomycin (100 ug/mL) to suppress the other bacteria, and
      differentiate C. kroppenstedtii from non-kroppenstedtii lipophilic corynebacteria
      by esculin hydrolysis. The medium was evaluated for its ability to support the
      growth of C. kroppenstedtii, selection and differentiation of C. kroppenstedtii
      from other bacteria in non-sterile clinical specimens. RESULTS: C. kroppenstedtii
      grew as 1-2 mm colonies with black halo on CKSM within 72 hours of incubation,
      compared with barely visible pinpoint colonies on routine blood agars. During the
      four-month period of evaluation with 8896 respiratory specimens, 103 breast
      specimens, 1903 female genital tract specimens, 617 newborn surface swabs and 10
      011 miscellaneous specimens, 186 C. kroppenstedtii were isolated, including 127
      (1.4%) respiratory and 59 (0.5%) miscellaneous specimens, 184 of them were found
      only on CKSM. Besides the three (2.9%) positive breast specimens, 27 (1.4%) high
      vaginal and endocervical swabs, and 11 (1.8%) surface swabs of newborns were
      positive for C. kroppenstedtii. CONCLUSIONS: CKSM is a useful addition to routine
      agar media for the isolation of C. kroppenstedtii, and will be helpful for
      studying the epidemiology and transmission of this unusual Corynebacterium
      causing granulomatous mastitis.

PMID- 29593063
TI  - Erratum for Sun et al., "Zoonotic Risk, Pathogenesis, and Transmission of Avian
      Origin H3N2 Canine Influenza Virus".

PMID- 29593064
TI  - A day in the life of chromatin: how enhancer-promoter loops shape daily behavior.
AB  - Each spring, we get out of bed 1 h ahead of our biological wake-up time due to
      the misalignment of internal clocks with the light-dark cycle. Genetic
      discoveries revealed that clock genes encode transcription factors that are
      expressed throughout many tissues, yet a gap has remained in understanding the
      temporal dynamics of transcription. Two groups now apply circular chromosome
      conformation capture and high-throughput sequencing to dissect how "time of day"
      dependent changes in chromatin drive core clock oscillations. A surprise is the
      finding that disruption of enhancer-promoter contacts within chromatin leads to
      an advance in the "wake-up" time of mice. Furthermore, the assembly of
      transcriptionally active domains of chromatin requires the ordered recruitment of
      core clock transcription factors each day. These studies show that waking up
      involves highly dynamic changes in the three-dimensional positioning of genes
      within the cell.

PMID- 29593065
TI  - A bone marrow niche-derived molecular switch between osteogenesis and
      hematopoiesis.
AB  - Hematopoietic stem cells (HSCs) reside and are maintained in specialized
      microenvironments within the bone marrow known as niches, which are comprised of
      various cell types. Among them, leptin receptor (LepR)-expressing CXC chemokine
      ligand 12 (CXCL12)-abundant reticular (CAR) cells are known to create a niche for
      HSCs and at the same time to give rise to osteoblasts. These two functions of
      CAR/LepR+ cells appear to be tightly but inversely regulated to ensure adequate
      physical space for HSCs. However, how osteogenesis is prevented in CAR cells to
      maintain spaces available for HSCs and hematopoiesis remains unclear. In this
      issue of Genes & Development, Seike and colleagues (pp. 359-372) report that the
      transcription factor early B-cell factor (Ebf3) is preferentially expressed by
      CAR/LepR+ cells and inhibits CAR cell differentiation into osteoblasts while at
      the same time maintaining self-renewal of CAR/LepR+ cells. Using conditional
      knockout and retroviral systems, the investigators show that loss of Ebf3 in CAR
      cells impairs HSC numbers and leads to osteosclerosis. This study provides novel
      insights into transcriptional requirements for CAR cell bone formation by
      identifying Ebf3 as a niche factor secreted from CAR/Lepr+ cells that regulates
      the interplay between osteogenesis and hematopoiesis.

PMID- 29593060
TI  - The British Society of Gastroenterology/UK-PBC primary biliary cholangitis
      treatment and management guidelines.
AB  - Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is
      an autoimmune liver disease in which a cycle of immune mediated biliary
      epithelial cell injury, cholestasis and progressive fibrosis can culminate over
      time in an end-stage biliary cirrhosis. Both genetic and environmental influences
      are presumed relevant to disease initiation. PBC is most prevalent in women and
      those over the age of 50, but a spectrum of disease is recognised in adult
      patients globally; male sex, younger age at onset (<45) and advanced disease at
      presentation are baseline predictors of poorer outcome. As the disease is
      increasingly diagnosed through the combination of cholestatic serum liver tests
      and the presence of antimitochondrial antibodies, most presenting patients are
      not cirrhotic and the term cholangitis is more accurate. Disease course is
      frequently accompanied by symptoms that can be burdensome for patients, and
      management of patients with PBC must address, in a life-long manner, both disease
      progression and symptom burden. Licensed therapies include ursodeoxycholic acid
      (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed
      agents. Disease management focuses on initiation of UDCA for all patients and
      risk stratification based on baseline and on-treatment factors, including in
      particular the response to treatment. Those intolerant of treatment with UDCA or
      those with high-risk disease as evidenced by UDCA treatment failure (frequently
      reflected in trial and clinical practice as an alkaline phosphatase >1.67 * upper
      limit of normal and/or elevated bilirubin) should be considered for second-line
      therapy, of which OCA is the only currently licensed National Institute for
      Health and Care Excellence recommended agent. Follow-up of patients is life-long
      and must address treatment of the disease and management of associated symptoms.

PMID- 29593067
TI  - Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in
      obese individuals.
AB  - Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial
      derived peptide that attenuates weight gain and hyperinsulinemia when
      administered to high fat-fed mice. MOTS-c is therefore a potential regulator of
      metabolic homeostasis under conditions of high-energy supply. However, the effect
      of insulin resistance and obesity on plasma MOTS-c concentration in humans is
      unknown. To gain insight into MOTS-c regulation, we measured plasma MOTS-c
      concentration and analyzed its relationship with insulin sensitivity surrogates,
      in lean and obese humans (n=10 per group). Obese individuals had impaired insulin
      sensitivity as indicated by low Matsuda and high Homeostatic Model Assessment
      (HOMA) indexes. Although plasma MOTS-c concentration was similar in lean and
      obese individuals (0.48+/-0.16 and 0.52+/-0.15 ng/mL; p=0.60), it was correlated
      with HOMA (r=0.53; p<0.05) and Matsuda index (r=-0.46; p<0.05). Notably, when the
      groups were analyzed separately, the associations remained only in lean
      individuals. We conclude that plasma MOTS-c concentration is unaltered in human
      obesity. However, MOTS-c associates positively with insulin resistance mostly in
      lean individuals, indicating that plasma MOTS-c concentration depends on the
      metabolic status in this population. Such dependence seems altered when obesity
      settles. The implications of plasma MOTS-c for human metabolic homeostasis
      deserve future examination.

PMID- 29593068
TI  - Ki-67 and condensins cooperate in mitotic chromosome assembly.

PMID- 29593069
TI  - Understanding the Hierarchical Organization of Large-Scale Networks Based on
      Temporal Modulations in Patterns of Neural Connectivity.

PMID- 29593066
TI  - Necroptosis in development and diseases.
AB  - Necroptosis, a form of regulated necrotic cell death mediated by RIPK1 (receptor
      interacting protein kinase 1) kinase activity, RIPK3, and MLKL (mixed-lineage
      kinase domain-like pseudokinase), can be activated under apoptosis-deficient
      conditions. Modulating the activation of RIPK1 by ubiquitination and
      phosphorylation is critical to control both necroptosis and apoptosis. Mutant
      mice with kinase-dead RIPK1 or RIPK3 and MLKL deficiency show no detrimental
      phenotype in regard to development and adult homeostasis. However, necroptosis
      and apoptosis can be activated in response to various mutations that result in
      the abortion of the defective embryos and human inflammatory and
      neurodegenerative pathologies. RIPK1 inhibition represents a key therapeutic
      strategy for treatment of diseases where blocking both necroptosis and apoptosis
      can be beneficial.

PMID- 29593070
TI  - Identifying the Unique Role of Notch3 in Adult Neural Stem Cell Maintenance.

PMID- 29593071
TI  - Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule
      Cell Synapses.
AB  - When an action potential invades a presynaptic terminal it evokes large, brief
      Ca2+ signals that trigger vesicle fusion within milliseconds that is followed by
      a small residual Ca2+ (Cares) signal. At many synapses Cares produces synaptic
      facilitation that lasts up to hundreds of milliseconds and, although less common,
      Cares can also evoke asynchronous release (AR) that persists for tens of
      milliseconds. The properties of facilitation and AR are very different, which
      suggests that they are mediated by distinct mechanisms. However, recently it has
      been shown that the slow calcium sensor synaptotagmin 7 (Syt7) mediates
      facilitation at many synapses where AR does not occur, and conversely Syt7 can
      mediate AR without mediating facilitation. Here we study cerebellar granule cell
      synapses onto stellate cells and Purkinje cells in mice of both sexes to assess
      the role of Syt7 in these phenomena at the same synapse. This is of particular
      interest at granule cell synapses where AR is much more calcium dependent and
      shorter-lived than facilitation. We find that Syt7 can mediate these two
      processes despite their divergent properties. In Syt7 knock-out animals,
      facilitation and AR are smaller and shorter lived than in wild-type animals, even
      though the initial probability of release and Cares signals are unchanged.
      Although there are short-lived Syt7-independent mechanisms that mediate
      facilitation and AR in Syt7 KO animals, we find that at granule cell synapses AR
      and facilitation are both mediated primarily by Syt7.SIGNIFICANCE STATEMENT At
      synapses made by cerebellar granule cells, presynaptic activity elevates calcium
      for tens of milliseconds, which in turn evokes both asynchronous release (AR) and
      synaptic facilitation. AR is more calcium sensitive and shorter-lived than
      facilitation at these synapses, suggesting that they are mediated by different
      mechanisms. However, we find that the slow calcium sensor synaptotagmin 7
      mediates both of these phenomena. Small, rapidly decaying components of AR and
      facilitation are present in Syt7 KO animals, indicating that additional
      mechanisms can contribute to both AR and facilitation at these synapses.

PMID- 29593072
TI  - A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations:
      Investigating the Endoderm Specifying Ability of the Intestinal Differentiation
      GATA Factor ELT-2.
AB  - The ELT-2 GATA factor normally functions in differentiation of the C. elegans
      endoderm, downstream of endoderm specification. We have previously shown that, if
      ELT-2 is expressed sufficiently early, it is also able to specify the endoderm
      and to replace all other members of the core GATA-factor transcriptional cascade
      (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and
      presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of
      the transgene does not rescue. We have made this observation the basis of a
      genetic screen to search for genetic modifiers that allow a single copy of the
      end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1 end-3 double
      mutant. We performed this screen on a strain that has a single copy insertion of
      the transgene in an end-1 end-3 background. These animals are kept alive by
      virtue of an extrachromosomal array containing multiple copies of the rescuing
      transgene; the extrachromosomal array also contains a toxin under heat shock
      control to counterselect for mutagenized survivors that have been able to lose
      the rescuing array. A screen of ~14,000 mutagenized haploid genomes produced 17
      independent surviving strains. Whole genome sequencing was performed to identify
      genes that incurred independent mutations in more than one surviving strain. The
      C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes
      the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has
      been found, in both mammals and insects, to cleave several proteins involved in
      transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was
      mutated in two independent strains and encodes a glutamine-asparagine rich
      protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end
      1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases,
      gene loss leads to modest increases in the level of ELT-2 protein in the early
      endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest
      that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to
      modulate levels of critical transcription factors or to modulate the
      responsiveness of critical target genes. The screen's design, rescuing lethality
      with an extrachromosomal transgene followed by counterselection, has a background
      survival rate of <10-4 without mutagenesis and should be readily adapted to the
      general problem of identifying suppressors of C. elegans lethal mutations.

PMID- 29593073
TI  - Vps74 Connects the Golgi Apparatus and Telomeres in Saccharomyces cerevisiae.
AB  - In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3,
      a Golgi component, is a phosphorylation target of DNA-PK after DNA damage and
      contributes to Golgi fragmentation. The function of the yeast (Saccharomyces
      cerevisiae) ortholog of GOLPH3, Vps74, in the DNA damage response has been little
      studied, although genome-wide screens suggested a role at telomeres. In this
      study we investigated the role of Vps74 at telomeres and in the DNA damage
      response. We show that Vps74 decreases the fitness of telomere defective cdc13-1
      cells and contributes to the fitness of yku70Delta cells. Importantly, loss of
      Vps74 in yku70Delta cells exacerbates the temperature dependent growth defects of
      these cells in a Chk1 and Mec1-dependent manner. Furthermore, Exo1 reduces the
      fitness of vps74Delta yku70Delta cells suggesting that ssDNA contributes to the
      fitness defects of vps74Delta yku70Delta cells. Systematic genetic interaction
      analysis of vps74Delta, yku70Delta and yku70Delta vps74Delta cells suggests that
      vps74Delta causes a milder but similar defect to that seen in yku70Delta cells.
      vps74Delta cells have slightly shorter telomeres and loss of VPS74 in yku70Delta
      or mre11Delta cells further shortens the telomeres of these cells. Interestingly,
      loss of Vps74 leads to increased levels of Stn1, a partner of Cdc13 in the CST
      telomere capping complex. Overexpression of Stn1 was previously shown to cause
      telomere shortening, suppression of cdc13-1 and enhancement of yku70Delta growth
      defects, suggesting that increased levels of Stn1 may be the route by which Vps74
      affects telomere function. These results establish Vps74 as a novel regulator of
      telomere biology.

PMID- 29593075
TI  - Support for the placement of Chilesaurus within Ornithischia: a reply to Muller
      et al.

PMID- 29593074
TI  - Comment on 'A dinosaur missing-link? Chilesaurus and the early evolution of
      ornithischian dinosaurs'.

PMID- 29593076
TI  - Reverse audience effects on helping in cooperatively breeding marmoset monkeys.
AB  - Cooperatively breeding common marmosets show substantial variation in the amount
      of help they provide. Pay-to-stay and social prestige models of helping attribute
      this variation to audience effects, i.e. that individuals help more if group
      members can witness their interactions with immatures, whereas models of kin
      selection, group augmentation or those stressing the need to gain parenting
      experience do not predict any audience effects. We quantified the readiness of
      adult marmosets to share food in the presence or absence of other group members.
      Contrary to both predictions, we found a reverse audience effect on food-sharing
      behaviour: marmosets would systematically share more food with immatures when no
      audience was present. Thus, helping in common marmosets, at least in related
      family groups, does not support the pay-to-stay or the social prestige model, and
      helpers do not take advantage of the opportunity to engage in reputation
      management. Rather, the results appear to reflect a genuine concern for the
      immatures' well-being, which seems particularly strong when solely responsible
      for the immatures.

PMID- 29593077
TI  - Selective screening for atrial fibrillation using multivariable risk models.
AB  - OBJECTIVE: Atrial fibrillation can lead to stroke if untreated, and identifying
      those at higher risk is necessary for cost-effective screening for asymptomatic,
      paroxysmal atrial fibrillation. Age has been proposed to identify those at risk,
      but risk models may provide better discrimination. This study compares atrial
      fibrillation risk models with age for screening for atrial fibrillation. METHODS:
      Nine atrial fibrillation risk models were compared using the Atherosclerosis Risk
      in Communities study (11 373 subjects, 60.0+/-5.7 years old). A new risk model
      (Screening for Asymptomatic Atrial Fibrillation Events-SAAFE) was created using
      data collected in the Monitoring Disparities in Chronic Conditions study (3790
      subjects, 58.9+/-15.3 years old). The primary measure was the fraction of
      incident atrial fibrillation subjects who should receive treatment due to a high
      CHA2DS2-VASc score identified when screening a fixed number equivalent to the age
      criterion. Secondary measures were the C statistic and net benefit. RESULTS: Five
      risk models were significantly better than age. Age identified 71 (61%) of the
      subjects at risk for stroke who subsequently developed atrial fibrillation, while
      the best risk model identified 96 (82%). The newly developed SAAFE model
      identified 95 (81%), primarily based on age, congestive heart failure and
      coronary artery disease. CONCLUSIONS: Use of a risk model increases
      identification of subjects at risk for atrial fibrillation. One of the best
      performing models (SAAFE) does not require an ECG for its application, so that it
      could be used instead of age as a screening criterion without adding to the cost.

PMID- 29593078
TI  - Aortic elongation part I: the normal aortic ageing process.
AB  - OBJECTIVES: Differentiation between normal and abnormal features of vascular
      ageing is crucial, as the latter is associated with adverse outcomes. The normal
      aortic ageing process is accompanied by gradual luminal dilatation and reduction
      of vessel compliance. However, the influence of age on longitudinal aortic
      dimensions and geometry has not been well studied. This study aims to describe
      the normal evolution of aortic length and shape throughout life. METHODS: A total
      of 210 consecutive patients were prospectively enrolled in this cross-sectional
      single-centre study. All subjects underwent CT on a third-generation dual-source
      CT scanner. Morphometric measurements, including measurements of segmental length
      and tortuosity, were performed on three-dimensional models of the thoracic aorta.
      RESULTS: The length of the thoracic aorta was significantly related to age
      (r=0.54) and increased by 59 mm (males) or 66 mm (females) between the ages of 20
      and 80 years. Elongation was most pronounced in the proximal descending aorta,
      which showed an almost 2.5-fold length increase during life. The lengthening of
      the thoracic aorta was accompanied by a marked change of its geometry: whereas
      the aortic apex was located between the branch vessels in younger patients, it
      shifted to a more distalward position in the elderly. CONCLUSIONS: The normal
      ageing process is accompanied by gradual aortic elongation and a notable change
      of aortic geometry. Part II of this two-part article investigates the hypothesis
      that excessive elongation could play a role in the occurrence of acute aortic
      dissection.

PMID- 29593079
TI  - Aortic elongation part II: the risk of acute type A aortic dissection.
AB  - OBJECTIVES: Prophylactic surgery for prevention of acute type A aortic dissection
      (ATAAD) is reserved for patients with an ascending aortic aneurysm >=55 mm.
      Identification of additional risk predictors is warranted since over 70% of
      patients presenting with ATAAD have a non-dilated aorta or an aneurysm that would
      not have met the diameter criterion for preventative surgery. Aim of the study
      was to evaluate ascending aortic elongation as a risk factor for ATAAD and to
      compare aortic lengths between ATAAD patients and healthy controls. METHODS:
      Aortic lengths and diameters of ATAAD patients were measured on three-dimensional
      modelled computed tomography and adjusted to predissection dimensions in this
      cross-sectional single-centre study. Logistic regression was used to evaluate the
      relation between ATAAD and aortic dimensions. Lengths of different aortic
      segments were compared with a healthy control group using propensity score
      matching. RESULTS: Two-hundred and fifty patients were included in the study
      (ATAAD, n=40; controls, n=210). Ascending aortic length and diameter proved to be
      independent predictors for ATAAD (OR=5.3, CI 2.5 to 11.4, p<0.001 and OR=8.6, CI
      2.4 to 31.0, p=0.001). Eighty patients were matched based on propensity scores
      (ATAAD n=40, controls n=40). The ascending aorta was longer and more dilated in
      ATAAD patients compared with healthy controls (78.6+/-8.8 mm vs 68.9+/-7.2 mm,
      p<0.001, 34.4 mm +/-3.2. vs 39.4 mm +/-5.7, p<0.001, respectively). No
      differences were found in lengths of the aortic arch and descending aorta.
      CONCLUSIONS: Ascending aortic length could serve as an independent predictor for
      ATAAD. Future studies addressing indications for prophylactic surgery should also
      investigate aortic length.

PMID- 29593080
TI  - Resistance to DNA damage and enhanced DNA repair capacity in the hypoxia-tolerant
      blind mole rat Spalax carmeli.
AB  - Blind mole rats of the genus Spalax are the only mammalian species to date for
      which spontaneous cancer has never been reported and resistance to carcinogen
      induced cancers has been demonstrated. However, the underlying mechanisms are
      still poorly understood. The fact that Spalax spp. are also hypoxia-tolerant and
      long-lived species implies the presence of molecular adaptations to prevent
      genomic instability, which underlies both cancer and aging. We previously
      demonstrated the upregulation of transcripts related to DNA replication and
      repair pathways in Spalax Yet, to date, no direct experimental evidence for
      improved genomic maintenance has been demonstrated for this genus. Here, we show
      that compared with skin fibroblasts of the above-ground rat, Spalax carmeli skin
      fibroblasts in culture resist several types of genotoxic insult, accumulate fewer
      genotoxic lesions and exhibit an enhanced DNA repair capacity. Our results
      strongly support that this species has evolved efficient mechanisms to maintain
      DNA integrity as an adaptation to the stressful conditions in the subterranean
      habitat.

PMID- 29593081
TI  - Cuticular gas exchange by Antarctic sea spiders.
AB  - Many marine organisms and life stages lack specialized respiratory structures,
      like gills, and rely instead on cutaneous respiration, which they facilitate by
      having thin integuments. This respiratory mode may limit body size, especially if
      the integument also functions in support or locomotion. Pycnogonids, or sea
      spiders, are marine arthropods that lack gills and rely on cutaneous respiration
      but still grow to large sizes. Their cuticle contains pores, which may play a
      role in gas exchange. Here, we examined alternative paths of gas exchange in sea
      spiders: (1) oxygen diffuses across pores in the cuticle, a common mechanism in
      terrestrial eggshells, (2) oxygen diffuses directly across the cuticle, a common
      mechanism in small aquatic insects, or (3) oxygen diffuses across both pores and
      cuticle. We examined these possibilities by modeling diffusive oxygen fluxes
      across all pores in the body of sea spiders and asking whether those fluxes
      differed from measured metabolic rates. We estimated fluxes across pores using
      Fick's law parameterized with measurements of pore morphology and oxygen
      gradients. Modeled oxygen fluxes through pores closely matched oxygen consumption
      across a range of body sizes, which means the pores facilitate oxygen diffusion.
      Furthermore, pore volume scaled hypermetrically with body size, which helps
      larger species facilitate greater diffusive oxygen fluxes across their cuticle.
      This likely presents a functional trade-off between gas exchange and structural
      support, in which the cuticle must be thick enough to prevent buckling due to
      external forces but porous enough to allow sufficient gas exchange.

PMID- 29593082
TI  - Heat- and humidity-induced plastic changes in body lipids and starvation
      resistance in the tropical fly Zaprionus indianus during wet and dry seasons.
AB  - Insects in tropical wet or dry seasons are likely to cope with starvation stress
      through plastic changes (developmental as well as adult acclimation) in energy
      metabolites. Control and experimental groups of Zaprionus indianus flies were
      reared under wet or dry conditions, but adults were acclimated at different
      thermal or humidity conditions. Adult flies of the control group were acclimated
      at 27 degrees C and low (50%) or high (60%) relative humidity (RH). For
      experimental groups, adult flies were acclimated at 32 degrees C for 1 to 6 days
      and under low (40%) or high (70%) RH. For humidity acclimation, adult flies were
      acclimated at 27 degrees C but under low (40%) or high (70%) RH for 1 to 6 days.
      Plastic changes in experimental groups as compared with the control group
      (developmental as well as adult acclimation) revealed significant accumulation of
      body lipids owing to thermal or humidity acclimation of wet season flies, but low
      humidity acclimation did not change the level of body lipids in dry season flies.
      Starvation resistance and body lipids were higher in the males of dry season
      flies but in the females of wet season flies. Adults acclimated under different
      thermal or humidity conditions exhibited changes in the rate of utilization of
      body lipids, carbohydrates and proteins. Adult acclimation of wet or dry season
      flies revealed plastic changes in mean daily fecundity; and a reduction in
      fecundity under starvation. Thus, thermal or humidity acclimation of adults
      revealed plastic changes in energy metabolites to support starvation resistance
      of wet or dry season flies.

PMID- 29593083
TI  - Presence and persistence of a highly ordered lipid phase state in the avian
      stratum corneum.
AB  - To survive high temperatures in a terrestrial environment, animals must
      effectively balance evaporative heat loss and water conservation. In passerine
      birds, cutaneous water loss (CWL) is the primary avenue of water loss at
      thermoneutral temperatures and increases slightly as ambient temperature
      increases, indicating a change in the permeability of the skin. In the stratum
      corneum (SC), the outermost layer of the skin, lipids arranged in layers called
      lamellae serve as the primary barrier to CWL in birds. The permeability of these
      lamellae depends in large part on the ability of lipid molecules to pack closely
      together in an ordered orthorhombic phase state. However, as temperature
      increases, lipids of the SC become more disordered, and may pack in more
      permeable hexagonal or liquid crystalline phase states. In this study, we used
      Fourier transform infrared spectroscopy to monitor the phase state of lipids in
      the SC of house sparrows (Passer domesticus) at skin temperatures ranging from 25
      to 50 degrees C. As temperature increased, lipids became slightly more
      disordered, but remained predominantly in the orthorhombic phase, consistent with
      the small increase in CWL observed in house sparrows as ambient temperature
      increases. These results differ considerably from studies on mammalian SC, which
      find a predominantly hexagonal arrangement of lipids at temperatures above 37
      degrees C, and the increased order in avian SC may be explained by longer lipid
      chain length, scarcity of cholesterol and the presence of cerebrosides. Our
      results lend further insight into the arrangement and packing of individual lipid
      molecules in avian SC.

PMID- 29593084
TI  - Flying Drosophilamelanogaster maintain arbitrary but stable headings relative to
      the angle of polarized light.
AB  - Animals must use external cues to maintain a straight course over long distances.
      In this study, we investigated how the fruit fly Drosophila melanogaster selects
      and maintains a flight heading relative to the axis of linearly polarized light,
      a visual cue produced by the atmospheric scattering of sunlight. To track flies'
      headings over extended periods, we used a flight simulator that coupled the
      angular velocity of dorsally presented polarized light to the stroke amplitude
      difference of the animals' wings. In the simulator, most flies actively
      maintained a stable heading relative to the axis of polarized light for the
      duration of 15 min flights. We found that individuals selected arbitrary,
      unpredictable headings relative to the polarization axis, which demonstrates that
      D. melanogaster can perform proportional navigation using a polarized light
      pattern. When flies flew in two consecutive bouts separated by a 5 min gap, the
      two flight headings were correlated, suggesting individuals retain a memory of
      their chosen heading. We found that adding a polarized light pattern to a light
      intensity gradient enhanced flies' orientation ability, suggesting D.
      melanogaster use a combination of cues to navigate. For both polarized light and
      intensity cues, flies' capacity to maintain a stable heading gradually increased
      over several minutes from the onset of flight. Our findings are consistent with a
      model in which each individual initially orients haphazardly but then settles on
      a heading which is maintained via a self-reinforcing process. This may be a
      general dispersal strategy for animals with no target destination.

PMID- 29593085
TI  - A model-based analysis of tissue targeting efficacy of nanoparticles.
AB  - Tissue targeting is a critical challenge for systemic delivery of drug
      nanocarriers. To overcome this challenge, major research efforts have been
      undertaken to design ligand-conjugated nanoparticles. However, limited work has
      been done to quantitatively assess the effectiveness of such approach. In this
      work, using a mechanistic spatio-temporal model, I investigate the effectiveness
      of ligand-directed tissue targeting. By applying an approach from the colloidal
      filtration theory, I develop a Brownian dynamics model of nanoparticle-cell
      interaction. The model incorporates a single cell and its surrounding flow field.
      It considers both specific (receptor-mediated) and non-specific (bare cell
      surface-mediated) recognition of nanoparticles subject to convective and
      diffusive motion. Using the model, I investigate how the specific and non
      specific interactions compare in determining the overall targeting efficacy. My
      analysis provides some interesting findings that contradict the general notion
      that effective targeting is possible based upon the differential receptor
      expression in cancer and non-cancer cells. I show that such strategy may yield
      only a marginal gain in the targeting efficacy. Moreover, non-specific
      interaction may have an important influence on particle recognition by cells even
      at high receptor expression levels.

PMID- 29593086
TI  - Dynamical patterns underlying response properties of cortical circuits.
AB  - Recent experimental studies show cortical circuit responses to external stimuli
      display varied dynamical properties. These include stimulus strength-dependent
      population response patterns, a shift from synchronous to asynchronous states and
      a decline in neural variability. To elucidate the mechanisms underlying these
      response properties and explore how they are mechanistically related, we develop
      a neural circuit model that incorporates two essential features widely observed
      in the cerebral cortex. The first feature is a balance between excitatory and
      inhibitory inputs to individual neurons; the second feature is distance-dependent
      connectivity. We show that applying a weak external stimulus to the model evokes
      a wave pattern propagating along lateral connections, but a strong external
      stimulus triggers a localized pattern; these stimulus strength-dependent
      population response patterns are quantitatively comparable with those measured in
      experimental studies. We identify network mechanisms underlying this population
      response, and demonstrate that the dynamics of population-level response patterns
      can explain a range of prominent features in neural responses, including changes
      to the dynamics of neurons' membrane potentials and synaptic inputs that
      characterize the shift of cortical states, and the stimulus-evoked decline in
      neuron response variability. Our study provides a unified population activity
      pattern-based view of diverse cortical response properties, thus shedding new
      insights into cortical processing.

PMID- 29593087
TI  - The external scent efferent system of selected European true bugs (Heteroptera):
      a biomimetic inspiration for passive, unidirectional fluid transport.
AB  - In this work, we present structured capillaries that were inspired by the
      microstructures of the external scent efferent system as found in different
      European true bug species (Pentatomidae and Cydnidae). These make use of small,
      orientated structures in order to facilitate fluid movement towards desired areas
      where defensive substances are evaporated. Gland channels and microstructures
      were investigated by means of scanning electron microscopy and abstracted into
      three-dimensional models. We used these models to create scent channel replicas
      from different technical substrates (steel and polymers) by means of laser
      ablation, laser structuring and casting. Video analysis of conducted fluid-flow
      experiments showed that bug-inspired, artificial scent fluid channels can indeed
      transport different fluids (water solutions and oils/lubricants) passively in one
      direction (velocities of up to 1 mm s-1), while halting the fluid movement in the
      opposite direction. At the end of this contribution, we present a physical theory
      that explains the observed fluid transport and sets the rules for performance
      optimization in future work.

PMID- 29593088
TI  - Robotic investigation on effect of stretch reflex and crossed inhibitory response
      on bipedal hopping.
AB  - To maintain balance during dynamic locomotion, the effects of proprioceptive
      sensory feedback control (e.g. reflexive control) should not be ignored because
      of its simple sensation and fast reaction time. Scientists have identified the
      pathways of reflexes; however, it is difficult to investigate their effects
      during locomotion because locomotion is controlled by a complex neural system and
      current technology does not allow us to change the control pathways in living
      humans. To understand these effects, we construct a musculoskeletal bipedal
      robot, which has similar body structure and dynamics to those of a human. By
      conducting experiments on this robot, we investigate the effects of reflexes
      (stretch reflex and crossed inhibitory response) on posture during hopping, a
      simple and representative bouncing gait with complex dynamics. Through over 300
      hopping trials, we confirm that both the stretch reflex and crossed response can
      contribute to reducing the lateral inclination during hopping. These reflexive
      pathways do not use any prior knowledge of the dynamic information of the body
      such as its inclination. Beyond improving the understanding of the human neural
      system, this study provides roboticists with biomimetic ideas for robot
      locomotion control.

PMID- 29593089
TI  - Language acquisition with communication between learners.
AB  - We consider a class of students learning a language from a teacher. The situation
      can be interpreted as a group of child learners receiving input from the
      linguistic environment. The teacher provides sample sentences. The students try
      to learn the grammar from the teacher. In addition to just listening to the
      teacher, the students can also communicate with each other. The students hold
      hypotheses about the grammar and change them if they receive counter evidence.
      The process stops when all students have converged to the correct grammar. We
      study how the time to convergence depends on the structure of the classroom by
      introducing and evaluating various complexity measures. We find that structured
      communication between students, although potentially introducing confusion, can
      greatly reduce some of the complexity measures. Our theory can also be
      interpreted as applying to the scientific process, where nature is the teacher
      and the scientists are the students.

PMID- 29593090
TI  - Expression patterns of cryptochrome genes in avian retina suggest involvement of
      Cry4 in light-dependent magnetoreception.
AB  - The light-dependent magnetic compass of birds provides orientation information
      about the spatial alignment of the geomagnetic field. It is proposed to be
      located in the avian retina, and be mediated by a light-induced, biochemical
      radical-pair mechanism involving cryptochromes as putative receptor molecules. At
      the same time, cryptochromes are known for their role in the negative feedback
      loop in the circadian clock. We measured gene expression of Cry1, Cry2 and Cry4
      in the retina, muscle and brain of zebra finches over the circadian day to assess
      whether they showed any circadian rhythmicity. We hypothesized that retinal
      cryptochromes involved in magnetoreception should be expressed at a constant
      level over the circadian day, because birds use a light-dependent magnetic
      compass for orientation not only during migration, but also for spatial
      orientation tasks in their daily life. Cryptochromes serving in circadian tasks,
      on the other hand, are expected to be expressed in a rhythmic (circadian)
      pattern. Cry1 and Cry2 displayed a daily variation in the retina as expected for
      circadian clock genes, while Cry4 expressed at constant levels over time. We
      conclude that Cry4 is the most likely candidate magnetoreceptor of the light
      dependent magnetic compass in birds.

PMID- 29593091
TI  - In vivo atomic force microscopy-infrared spectroscopy of bacteria.
AB  - A new experimental platform for probing nanoscale molecular changes in living
      bacteria using atomic force microscopy-infrared (AFM-IR) spectroscopy is
      demonstrated. This near-field technique is eminently suited to the study of
      single bacterial cells. Here, we report its application to monitor dynamical
      changes occurring in the cell wall during cell division in Staphylococcus aureus
      using AFM to demonstrate the division of the cell and AFM-IR to record spectra
      showing the thickening of the septum. This work was followed by an investigation
      into single cells, with particular emphasis on cell-wall signatures, in several
      bacterial species. Specifically, mainly cell wall components from S. aureus and
      Escherichia coli containing complex carbohydrate and phosphodiester groups,
      including peptidoglycans and teichoic acid, could be identified and mapped at
      nanometre spatial resolution. Principal component analysis of AFM-IR spectra of
      six living bacterial species enabled the discrimination of Gram-positive from
      Gram-negative bacteria based on spectral bands originating mainly from the cell
      wall components. The ability to monitor in vivo molecular changes during cellular
      processes in bacteria at the nanoscale opens a new platform to study
      environmental influences and other factors that affect bacterial chemistry.

PMID- 29593092
TI  - The early mature part of bacterial twin-arginine translocation (Tat) precursor
      proteins contributes to TatBC receptor binding.
AB  - The twin-arginine translocation (Tat) pathway transports folded proteins across
      bacterial membranes. Tat precursor proteins possess a conserved twin-arginine
      (RR) motif in their signal peptides that is involved in the binding of the
      proteins to the membrane-associated TatBC receptor complex. In addition, the
      hydrophobic region in the Tat signal peptides also contributes to TatBC binding,
      but whether regions beyond the signal-peptide cleavage site are involved in this
      process is unknown. Here, we analyzed the contribution of the early mature
      protein part of the Escherichia coli trimethylamine N-oxide reductase (TorA) to
      productive TatBC receptor binding. We identified substitutions in the 30 amino
      acids immediately following the TorA signal peptide (30aa-region) that restored
      export of a transport-defective TorA[KQ]-30aa-MalE precursor, in which the RR
      residues had been replaced by a lysine-glutamine pair. Some of these
      substitutions increased the hydrophobicity of the N-terminal part of the 30aa
      region and thereby likely enhanced hydrophobic substrate-receptor interactions
      within the hydrophobic TatBC substrate-binding cavity. Another class of
      substitutions increased the positive net charge of the region's C-terminal part,
      presumably leading to strengthened electrostatic interactions between the mature
      substrate part and the cytoplasmic TatBC regions. Furthermore, we identified
      substitutions in the C-terminal domains of TatB following the transmembrane
      segment that restored transport of various transport-defective TorA-MalE
      derivatives. Some of these substitutions most likely affected the orientation or
      conformation of the flexible, carboxy-proximal helices of TatB. Therefore, we
      propose that a tight accommodation of the folded mature region by TatB
      contributes to productive binding of Tat substrates to TatBC.

PMID- 29593093
TI  - TAILS N-terminomics and proteomics reveal complex regulation of proteolytic
      cleavage by O-glycosylation.
AB  - Proteolytic processing is an irreversible post-translational modification
      functioning as a ubiquitous regulator of cellular activity. Protease activity is
      tightly regulated via control of gene expression, enzyme and substrate
      compartmentalization, zymogen activation, enzyme inactivation, and substrate
      availability. Emerging evidence suggests that proteolysis can also be regulated
      by substrate glycosylation and that glycosylation of individual sites on a
      substrate can decrease or, in rare cases, increase its sensitivity to
      proteolysis. Here, we investigated the relationship between site-specific, mucin
      type (or GalNAc-type) O-glycosylation and proteolytic cleavage of extracellular
      proteins. Using in silico analysis, we found that O-glycosylation and cleavage
      sites are significantly associated with each other. We then used a positional
      proteomic strategy, terminal amine isotopic labeling of substrates (TAILS), to
      map the in vivo cleavage sites in HepG2 SimpleCells with and without one of the
      key initiating GalNAc transferases, GalNAc-T2, and after treatment with exogenous
      matrix metalloproteinase 9 (MMP9) or neutrophil elastase. Surprisingly, we found
      that loss of GalNAc-T2 not only increased cleavage, but also decreased cleavage
      across a broad range of other substrates, including key regulators of the
      protease network. We also found altered processing of several central regulators
      of lipid homeostasis, including apolipoprotein B and the phospholipid transfer
      protein, providing new clues to the previously reported link between GALNT2 and
      lipid homeostasis. In summary, we show that loss of GalNAc-T2 O-glycosylation
      leads to a general decrease in cleavage and that GalNAc-T2 O-glycosylation
      affects key regulators of the cellular proteolytic network, including multiple
      members of the serpin family.

PMID- 29593094
TI  - Distinct human alpha(1,3)-fucosyltransferases drive Lewis-X/sialyl Lewis-X
      assembly in human cells.
AB  - In humans, six alpha(1,3)-fucosyltransferases (alpha(1,3)-FTs:
      FT3/FT4/FT5/FT6/FT7/FT9) reportedly fucosylate terminal lactosaminyl glycans
      yielding Lewis-X (LeX; CD15) and/or sialyl Lewis-X (sLeX; CD15s), structures that
      play key functions in cell migration, development, and immunity. Prior studies
      analyzing alpha(1,3)-FT specificities utilized either purified and/or recombinant
      enzymes to modify synthetic substrates under nonphysiological reaction conditions
      or molecular biology approaches wherein alpha(1,3)-FTs were expressed in
      mammalian cell lines, notably excluding investigations using primary human cells.
      Accordingly, although significant insights into alpha(1,3)-FT catalytic
      properties have been obtained, uncertainty persists regarding their human
      LeX/sLeX biosynthetic range across various glycoconjugates. Here, we undertook a
      comprehensive evaluation of the lactosaminyl product specificities of
      intracellularly expressed alpha(1,3)-FTs using a clinically relevant primary
      human cell type, mesenchymal stem cells. Cells were transfected with modified
      mRNA encoding each human alpha(1,3)-FT, and the resultant alpha(1,3)-fucosylated
      lactosaminyl glycoconjugates were analyzed using a combination of flow cytometry
      and MS. The data show that biosynthesis of sLeX is driven by FTs-3, -5, -6, and 
      7, with FT6 and FT7 having highest potency. FT4 and FT9 dominantly biosynthesize
      LeX, and, among all FTs, FT6 holds a unique capacity in creating sLeX and LeX
      determinants across protein and lipid glycoconjugates. Surprisingly, FT4 does not
      generate sLeX on glycolipids, and neither FT4, FT6, nor FT9 synthesizes the
      internally fucosylated sialyllactosamine VIM-2 (CD65s). These results unveil the
      relevant human lactosaminyl glycans created by human alpha(1,3)-FTs, providing
      novel insights on how these isoenzymes stereoselectively shape biosynthesis of
      vital glycoconjugates, thereby biochemically programming human cell migration and
      tuning human immunologic and developmental processes.

PMID- 29593095
TI  - Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78
      and fail to induce endoplasmic reticulum stress when retained.
AB  - The proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a central role in
      cardiovascular disease (CVD) by degrading hepatic low-density lipoprotein
      receptor (LDLR). As such, loss-of-function (LOF) PCSK9 variants that fail to exit
      the endoplasmic reticulum (ER) increase hepatic LDLR levels and lower the risk of
      developing CVD. The retention of misfolded protein in the ER can cause ER stress
      and activate the unfolded protein response (UPR). In this study, we investigated
      whether a variety of LOF PCSK9 variants that are retained in the ER can cause ER
      stress and hepatic cytotoxicity. Although overexpression of these PCSK9 variants
      caused an accumulation in the ER of hepatocytes, UPR activation or apoptosis was
      not observed. Furthermore, ER retention of endogenous PCSK9 via splice switching
      also failed to induce the UPR. Consistent with these in vitro studies,
      overexpression of PCSK9 in the livers of mice had no impact on UPR activation. To
      elucidate the cellular mechanism to explain these surprising findings, we
      observed that the 94-kDa glucose-regulated protein (GRP94) sequesters PCSK9 away
      from the 78-kDa glucose-regulated protein (GRP78), the major activator of the
      UPR. As a result, GRP94 knockdown increased the stability of GRP78-PCSK9 complex
      and resulted in UPR activation following overexpression of ER-retained PCSK9
      variants relative to WT secreted controls. Given that overexpression of these LOF
      PCSK9 variants does not cause UPR activation under normal homeostatic conditions,
      therapeutic strategies aimed at blocking the autocatalytic cleavage of PCSK9 in
      the ER represent a viable strategy for reducing circulating PCSK9.

PMID- 29593096
TI  - Myristoylated methionine sulfoxide reductase A is a late endosomal protein.
AB  - Methionine residues in proteins provide antioxidant defense by reacting with
      oxidizing species, which oxidize methionine to methionine sulfoxide. Reduction of
      the sulfoxide back to methionine is catalyzed by methionine sulfoxide reductases,
      essential for protection against oxidative stress. The nonmyristoylated form of
      methionine sulfoxide reductase A (MSRA) is present in mitochondria, whereas the
      myristoylated form has been previously reported to be cytosolic. Despite the
      importance of MSRA in antioxidant defense, its in vivo binding partners and
      substrates have not been identified. Starting with a protein array, and followed
      by immunoprecipitation experiments, colocalization studies, and subcellular
      fractionation, we identified the late endosomal protein, StAR-related lipid
      transfer domain-containing 3 (STARD3), as a binding partner of myristoylated
      MSRA, but not of nonmyristoylated MSRA. STARD3 is known to have both membrane
      binding and cytosolic domains that are important in STARD3-mediated transport of
      cholesterol from the endoplasmic reticulum to the endosome. We found that the
      STARD3 cytosolic domain localizes MSRA to the late endosome. We propose that the
      previous conclusion that myristoylated MSRA is strictly a cytosolic protein is
      artifactual and likely due to vigorous overexpression of MSRA. We conclude that
      myristoylated MSRA is a late endosomal protein that may play a role in lipid
      metabolism or may protect endosomal proteins from oxidative damage.

PMID- 29593097
TI  - Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6
      bisphosphate aldolases.
AB  - Crystal structures of two bacterial metal (Zn2+)-dependent d-fructose-1,6
      bisphosphate (FBP) aldolases in complex with substrate, analogues, and triose-P
      reaction products were determined to 1.5-2.0 A resolution. The ligand complexes
      cryotrapped in native or mutant Helicobacter pylori aldolase crystals enabled a
      novel mechanistic description of FBP C3-C4 bond cleavage. The reaction mechanism
      uses active site remodeling during the catalytic cycle, implicating relocation of
      the Zn2+ cofactor that is mediated by conformational changes of active site
      loops. Substrate binding initiates conformational changes triggered upon P1
      phosphate binding, which liberates the Zn2+-chelating His-180, allowing it to act
      as a general base for the proton abstraction at the FBP C4 hydroxyl group. A
      second zinc-chelating His-83 hydrogen bonds the substrate C4 hydroxyl group and
      assists cleavage by stabilizing the developing negative charge during proton
      abstraction. Cleavage is concerted with relocation of the metal cofactor from an
      interior to a surface-exposed site, thereby stabilizing the nascent enediolate
      form. Conserved residue Glu-142 is essential for protonation of the enediolate
      form prior to product release. A d-tagatose 1,6-bisphosphate enzymatic complex
      reveals how His-180-mediated proton abstraction controls stereospecificity of the
      cleavage reaction. Recognition and discrimination of the reaction products,
      dihydroxyacetone-P and d-glyceraldehyde 3-P, occurs via charged hydrogen bonds
      between hydroxyl groups of the triose-Ps and conserved residues, Asp-82 and Asp
      255, respectively, and are crucial aspects of the enzyme's role in
      gluconeogenesis. Conformational changes in mobile loops beta5-alpha7 and beta6
      alpha8 (containing catalytic residues Glu-142 and His-180, respectively) drive
      active site remodeling, enabling the relocation of the metal cofactor.

PMID- 29593098
TI  - Administration of the Tablet Formulation of Olaparib in Patients with Ovarian
      Cancer: Practical Guidance and Expectations.
AB  - : Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for
      use in patients with advanced ovarian cancer (OC) and genetic BRCA1/2 mutations
      who have received three or more prior lines of chemotherapy for maintenance
      treatment of recurrent OC that is in response to platinum-based chemotherapy
      regardless of BRCA mutation status and for human epidermal growth receptor factor
      2-negative metastatic breast cancer with deleterious or suspected deleterious
      germline BRCA mutations who have previously been treated with chemotherapy in the
      neoadjuvant, adjuvant, or metastatic setting. Because olaparib is poorly soluble
      and requires advanced drug delivery techniques to ensure bioavailability, the
      originally approved 400 mg dose is taken as eight 50 mg capsules twice daily. An
      alternative melt-extrusion tablet formulation was developed to improve the
      pharmacokinetic and pharmacodynamic profile of olaparib and reduce the pill
      burden for patients. The recommended tablet dose is 300 mg twice daily (two 150
      mg tablets). Phase III studies with the tablet formulation are ongoing for
      multiple tumor types. Two studies conducted with the olaparib tablet formulation
      have reported results: one in platinum-sensitive, BRCA-mutated recurrent OC (SOLO
      2) and one that included patients with germline BRCA-mutated metastatic breast
      cancer (OlympiAD). The tablet is the approved formulation based on the SOLO-2
      trial results. Because the capsule and tablet formulations have different
      bioavailability, physicians must strictly adhere to the dosing instructions
      provided in the prescribing information. The tablet offers greater convenience
      for most patients, especially when using olaparib for maintenance therapy. This
      review discusses the differences between the two formulations, dose
      determination, and guidance for use of olaparib tablets by patients with OC.
      Prior to implementing any changes in therapy, health care providers should engage
      their patients in discussion to support an informed transition between the
      formulations. IMPLICATIONS FOR PRACTICE: Olaparib has recently been approved for
      maintenance treatment of recurrent ovarian cancer (OC) that is in response to
      platinum-based chemotherapy. The originally approved capsule formulation was
      dosed as 400 mg twice daily (eight 50 mg capsules). The recommended olaparib
      tablet dose is 300 mg twice daily (two 150 mg tablets). The tablet is the new
      approved formulation based on the SOLO-2 trial results. Because the capsule and
      tablet formulations have different bioavailability, physicians must strictly
      adhere to the dosing instructions provided in the prescribing information. The
      tablet offers greater convenience for most patients, especially when using
      olaparib for maintenance therapy. This review discusses the differences between
      the two formulations, dose determination, and guidance for use of olaparib
      tablets by patients with OC.

PMID- 29593099
TI  - Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan-Class I PI3K
      Inhibitor, in Patients with Advanced Solid Tumors.
AB  - LESSONS LEARNED: A phase I study of the pan-class I phosphoinositide 3-kinase
      inhibitor pilaralisib (in capsule formulation) in advanced solid tumors
      established the maximum tolerated dose as 600 mg once daily.The current study
      investigated pilaralisib in tablet formulation.Pilaralisib tablets were
      associated with a favorable safety profile and preliminary antitumor
      activity.Based on pharmacokinetic data, the recommended phase II dose of
      pilaralisib tablets was established as 400 mg once daily. BACKGROUND: A phase I
      trial of pilaralisib, an oral pan-class I phosphoinositide 3-kinase (PI3K)
      inhibitor, established the maximum tolerated dose (MTD) of the capsule
      formulation in patients with advanced solid tumors as 600 mg once daily. This
      phase I study investigated pilaralisib in tablet formulation. MATERIALS AND
      METHODS: Patients with advanced solid tumors received pilaralisib tablets (100
      600 mg once daily). Primary endpoints were MTD and safety; secondary and
      exploratory endpoints included pharmacokinetics (PK), pharmacodynamics, and
      efficacy. RESULTS: Twenty-two patients were enrolled. No dose-limiting toxicities
      (DLTs) were reported. The most common treatment-related adverse events were
      diarrhea (40.9%), fatigue (40.9%), decreased appetite (22.7%), and hyperglycemia
      (22.7%). Pilaralisib plasma exposure did not appear to increase dose
      proportionally. Steady-state exposure was higher with pilaralisib tablet
      formulation at 400 mg than with pilaralisib capsule formulation at 400 or 600 mg
      (mean area under the curve [AUC0-24] 2,820,000 ng * h/mL vs. 2,653,000 and
      1,930,000 ng * h/mL, respectively). Of 18 evaluable patients, 2 (11.1%) had a
      partial response (PR). CONCLUSION: Pilaralisib tablets were associated with a
      favorable safety profile and preliminary antitumor activity. MTD was not
      determined. The recommended phase II dose for pilaralisib tablets, based on PK
      data, was 400 mg once daily.

PMID- 29593100
TI  - Development and Validation of a Clinical Score for Cardiovascular Risk
      Stratification of Long-Term Childhood Cancer Survivors.
AB  - BACKGROUND: Long-term childhood cancer survivors (CCS) are at increased risk of
      adverse cardiovascular events; however, there is a paucity of risk-stratification
      tools to identify those at higher-than-normal risk. SUBJECTS, MATERIALS, AND
      METHODS: This was a population-based study using data from the Surveillance,
      Epidemiology, and End Results Program (1973-2013). Long-term CCS (age at
      diagnosis <=19 years, survival >=5 years) were followed up over a median time
      period of 12.3 (5-40.9) years. Independent predictors of cardiovascular mortality
      (CVM) were combined into a risk score, which was developed in a derivation set (n
      = 22,374), and validated in separate patient registries (n = 6,437). RESULTS: In
      the derivation registries, older age at diagnosis (>=10 years vs. reference group
      of 1-5 years), male sex, non-white race, a history of lymphoma, and a history of
      radiation were independently associated with an increased risk of CVM among long
      term CCS (p < .05). A risk score derived from this model (Childhood and
      Adolescence Cancer Survivor CardioVascular score [CHACS-CV], range: 0-8) showed
      good discrimination for CVM (Harrell's C-index [95% confidence interval (CI)]:
      0.73 [0.68-0.78], p < .001) and identified a high-risk group (CHACS-CV >=6), with
      cumulative CVM incidence over 30 years of 6.0% (95% CI: 4.3%-8.1%) versus 2.6%
      (95% CI: 1.8%-3.7%), and 0.7% (95% CI: 0.5%-1.0%) in the mid- (CHACS-CV = 4-5)
      and low-risk groups (CHACS-CV <=3), respectively (plog-rank < .001). In the
      validation set, the respective cumulative incidence rates were 4.7%, 3.1%, and
      0.8% (plog-rank < .001). CONCLUSION: We propose a simple risk score that can be
      applied in everyday clinical practice to identify long-term CCS at increased
      cardiovascular risk, who may benefit from early cardiovascular screening, and
      risk-reduction strategies. IMPLICATIONS FOR PRACTICE: Childhood cancer survivors
      (CCS) are known to be at increased cardiovascular risk. Currently available
      prognostic tools focus on treatment-related adverse events and late development
      of congestive heart failure, but there is no prognostic model to date to estimate
      the risk of cardiovascular mortality among long-term CCS. A simple clinical tool
      is proposed for cardiovascular risk stratification of long-term CCS based on
      easily obtainable information from their medical history. This scoring system may
      be used as a first-line screening tool to assist health care providers in
      identifying those who may benefit from closer follow-up and enable timely
      deployment of preventive strategies.

PMID- 29593101
TI  - Thalidomide Reduces Hemorrhage of Brain Arteriovenous Malformations in a Mouse
      Model.
AB  - BACKGROUND AND PURPOSE: Brain arteriovenous malformation (bAVM) is an important
      risk factor for intracranial hemorrhage. Current treatments for bAVM are all
      associated with considerable risks. There is no safe method to prevent bAVM
      hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary
      hemorrhagic telangiectasia, an inherited disorder characterized by vascular
      malformations. In this study, we tested whether thalidomide and its less toxic
      analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. METHODS: bAVMs
      were induced through induction of brain focal activin-like kinase 1 (Alk1, an AVM
      causative gene) gene deletion and angiogenesis in adult Alk1-floxed mice.
      Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting
      either 2 or 8 weeks after AVM induction. Lenalidomide was injected
      intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain
      samples were collected at the end of the treatments for morphology, mRNA, and
      protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived
      growth factor B) expression was also studied on cultured human brain
      microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in
      bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the
      mouse brain. RESULTS: Thalidomide or lenalidomide treatment reduced the number of
      dysplastic vessels and hemorrhage and increased mural cell (vascular smooth
      muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the
      burden of CD68+ cells and the expression of inflammatory cytokines in the bAVM
      lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular
      endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb
      expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of
      thalidomide. CONCLUSIONS: Thalidomide and lenalidomide improve mural cell
      coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through
      upregulation of Pdgfb expression.

PMID- 29593102
TI  - A conserved transcriptional response to intranasal Ebola virus exposure in
      nonhuman primates prior to onset of fever.
AB  - Ebola virus disease (EVD), caused by Ebola virus (EBOV), is a severe illness
      characterized by case fatality rates of up to 90%. The sporadic nature of
      outbreaks in resource-limited areas has hindered the ability to characterize the
      pathogenesis of EVD at all stages of infection but particularly early host
      responses. Pathogenesis is often studied in nonhuman primate (NHP) models of
      disease that replicate major aspects of human EVD. Typically, NHP models use a
      large infectious dose, are carried out through intramuscular or aerosol exposure,
      and have a fairly uniform disease course. By contrast, we report our analysis of
      the host response to EBOV after intranasal exposure. Twelve cynomolgus macaques
      were infected with 100 plaque-forming units of EBOV/Makona through intranasal
      exposure and presented with varying times to onset of EVD. We used RNA sequencing
      and a newly developed NanoString CodeSet to monitor the host response via changes
      in RNA transcripts over time. When individual animal gene expression data were
      phased based on the onset of sustained fever, the first clinical sign of severe
      disease, mathematical models indicated that interferon-stimulated genes appeared
      as early as 4 days before fever onset. This demonstrates that lethal EVD has a
      uniform and predictable response to infection regardless of time to onset.
      Furthermore, expression of a subset of genes could predict disease development
      before other host-based indications of infection such as fever.

PMID- 29593103
TI  - The impact of past vaccination coverage and immunity on pertussis resurgence.
AB  - The resurgence of pertussis over the past decades has resulted in incidence
      levels not witnessed in the United States since the 1950s. The underlying causes
      have been the subject of much speculation, with particular attention paid to the
      shortcomings of the latest generation of vaccines. We formulated transmission
      models comprising competing hypotheses regarding vaccine failure and challenged
      them to explain 16 years of highly resolved incidence data from Massachusetts,
      United States. Our results suggest that the resurgence of pertussis is a
      predictable consequence of incomplete historical coverage with an imperfect
      vaccine that confers slowly waning immunity. We found evidence that the vaccine
      itself is effective at reducing overall transmission, yet that routine
      vaccination alone would be insufficient for elimination of the disease. Our
      results indicated that the core transmission group is schoolchildren. Therefore,
      efforts aimed at curtailing transmission in the population at large, and
      especially in vulnerable infants, are more likely to succeed if targeted at
      schoolchildren, rather than adults.

PMID- 29593105
TI  - Medication development in opioid addiction: Meaningful clinical end points.
AB  - The FDA's "abstinence" outcome measure for approval of new medications to treat
      opioid-use disorders has been difficult to achieve; developing and validating
      alternative meaningful outcomes could facilitate drug development.

PMID- 29593104
TI  - Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in
      lupus.
AB  - The earliest autoantibodies in lupus are directed against the RNA binding
      autoantigen Ro60, but the triggers against this evolutionarily conserved antigen
      remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and
      gut commensal bacterial species and confirmed the presence of these orthologs in
      patients with lupus and healthy controls. Thus, we hypothesized that commensal
      Ro60 orthologs may trigger autoimmunity via cross-reactivity in genetically
      susceptible individuals. Sera from human anti-Ro60-positive lupus patients
      immunoprecipitated commensal Ro60 ribonucleoproteins. Human Ro60 autoantigen
      specific CD4 memory T cell clones from lupus patients were activated by skin and
      mucosal Ro60-containing bacteria, supporting T cell cross-reactivity in humans.
      Further, germ-free mice spontaneously initiated anti-human Ro60 T and B cell
      responses and developed glomerular immune complex deposits after monocolonization
      with a Ro60 ortholog-containing gut commensal, linking anti-Ro60 commensal
      responses in vivo with the production of human Ro60 autoantibodies and signs of
      autoimmunity. Together, these data support that colonization with autoantigen
      ortholog-producing commensal species may initiate and sustain chronic
      autoimmunity in genetically predisposed individuals. The concept of commensal
      ortholog cross-reactivity may apply more broadly to autoimmune diseases and lead
      to novel treatment approaches aimed at defined commensal species.

PMID- 29593106
TI  - Ablation of the stress protease OMA1 protects against heart failure in mice.
AB  - Heart failure (HF) is a major health and economic burden in developed countries.
      It has been proposed that the pathogenesis of HF may involve the action of
      mitochondria. We evaluate three different mouse models of HF:
      tachycardiomyopathy, HF with preserved left ventricular (LV) ejection fraction
      (LVEF), and LV myocardial ischemia and hypertrophy. Regardless of whether LVEF is
      preserved, our results indicate that the three models share common features: an
      increase in mitochondrial reactive oxygen species followed by ultrastructural
      alterations in the mitochondrial cristae and loss of mitochondrial integrity that
      lead to cardiomyocyte death. We show that the ablation of the mitochondrial
      protease OMA1 averts cardiomyocyte death in all three murine HF models, and thus
      loss of OMA1 plays a direct role in cardiomyocyte protection. This finding
      identifies OMA1 as a potential target for preventing the progression of
      myocardial damage in HF associated with a variety of etiologies.

PMID- 29593107
TI  - Social enforcement depending on the stage of colony growth in an ant.
AB  - Altruism is a paradox in Darwinian evolution. Policing is an important mechanism
      of the evolution and maintenance of altruism. A recently developed dynamic game
      model incorporating colony demography and inclusive fitness predicts that, in
      hymenopteran social insects, policing behaviour enforcing reproductive altruism
      in group members depends strongly on the colony growth stage, with strong
      policing as the colony develops and a relaxation of policing during the
      reproductive phase. Here, we report clear evidence supporting this prediction. In
      the ant Diacamma sp., reproduction by workers was suppressed by worker policing
      when the colony was small, whereas in large, mature colonies worker policing was
      relaxed and worker-produced males emerged. Conditional expression of traits can
      provide strong empirical evidence for natural selection theory if the expression
      pattern is precisely predicted by the theory, and our results illustrate the
      importance of intracolony population dynamics in the evolution of social systems.

PMID- 29593108
TI  - Artificial light at night shifts daily activity patterns but not the internal
      clock in the great tit (Parus major).
AB  - Artificial light at night has shown a dramatic increase over the last decades and
      continues to increase. Light at night can have strong effects on the behaviour
      and physiology of species, which includes changes in the daily timing of
      activity; a clear example is the advance in dawn song onset in songbirds by low
      levels of light at night. Although such effects are often referred to as changes
      in circadian timing, i.e. changes to the internal clock, two alternative
      mechanisms are possible. First, light at night can change the timing of clock
      controlled activity, without any change to the clock itself; e.g. by a change in
      the phase relation between the circadian clock and expression of activity.
      Second, changes in daily activity can be a direct response to light ('masking'),
      without any involvement of the circadian system. Here, we studied whether the
      advance in onset of activity by dim light at night in great tits (Parus major) is
      indeed attributable to a phase shift of the internal clock. We entrained birds to
      a normal light/dark (LD) cycle with bright light during daytime and darkness at
      night, and to a comparable (LDim) schedule with dim light at night. The dim light
      at night strongly advanced the onset of activity of the birds. After at least six
      days in LD or LDim, we kept birds in constant darkness (DD) by leaving off all
      lights so birds would revert to their endogenous, circadian system controlled
      timing of activity. We found that the timing of onset in DD was not dependent on
      whether the birds were kept at LD or LDim before the measurement. Thus, the
      advance of activity under light at night is caused by a direct effect of light
      rather than a phase shift of the internal clock. This demonstrates that birds are
      capable of changing their daily activity to low levels of light at night
      directly, without the need to alter their internal clock.

PMID- 29593109
TI  - To eat or not to eat: ontogeny of hypothalamic feeding controls and a role for
      leptin in modulating life-history transition in amphibian tadpoles.
AB  - Many animal life histories entail changing feeding ecology, but the molecular
      bases for these transitions are poorly understood. The amphibian tadpole is
      typically a growth and dispersal life-history stage. Tadpoles are primarily
      herbivorous, and they capitalize on growth opportunities to reach a minimum body
      size to initiate metamorphosis. During metamorphic climax, feeding declines, at
      which time the gastrointestinal (GI) tract remodels to accommodate the
      carnivorous diet of the adult frog. Here we show that anorexigenic hypothalamic
      feeding controls are absent in the tadpole, but develop during metamorphosis
      concurrent with the production of the satiety signal leptin. Before metamorphosis
      there is a large increase in leptin mRNA in fat tissue. Leptin receptor mRNA
      increased during metamorphosis in the preoptic area/hypothalamus, the key brain
      region involved with the control of food intake and metabolism. This corresponded
      with an increase in functional leptin receptor, as evidenced by induction of
      socs3 mRNA and phosphorylated STAT3 immunoreactivity, and suppression of feeding
      behaviour after injection of recombinant frog leptin. Furthermore, we found that
      immunoneutralization of leptin in tadpoles at metamorphic climax caused them to
      resume feeding. The absence of negative regulation of food intake in the tadpole
      allows the animal to maximize growth prior to metamorphosis. Maturation of leptin
      responsive neural circuits suppresses feeding during metamorphosis to facilitate
      remodelling of the GI tract.

PMID- 29593110
TI  - Genetic rescue in an inbred Arctic fox (Vulpes lagopus) population.
AB  - Isolation of small populations can reduce fitness through inbreeding depression
      and impede population growth. Outcrossing with only a few unrelated individuals
      can increase demographic and genetic viability substantially, but few studies
      have documented such genetic rescue in natural mammal populations. We investigate
      the effects of immigration in a subpopulation of the endangered Scandinavian
      arctic fox (Vulpes lagopus), founded by six individuals and isolated for 9 years
      at an extremely small population size. Based on a long-term pedigree (105
      litters, 543 individuals) combined with individual fitness traits, we found
      evidence for genetic rescue. Natural immigration and gene flow of three outbred
      males in 2010 resulted in a reduction in population average inbreeding
      coefficient (f), from 0.14 to 0.08 within 5 years. Genetic rescue was further
      supported by 1.9 times higher juvenile survival and 1.3 times higher breeding
      success in immigrant first-generation offspring compared with inbred offspring.
      Five years after immigration, the population had more than doubled in size and
      allelic richness increased by 41%. This is one of few studies that has documented
      genetic rescue in a natural mammal population suffering from inbreeding
      depression and contributes to a growing body of data demonstrating the vital
      connection between genetics and individual fitness.

PMID- 29593111
TI  - Concede or clash? Solitary sharks competing for food assess rivals to decide.
AB  - To adapt to their environment, organisms can either directly interact with their
      surroundings or use social information (i.e. information provided by neighbouring
      individuals). Social information relates to the external features of surrounding
      peers, and little is known about its use by solitary species. Here, we
      investigated the use of social cues in a solitary marine predator by creating
      artificial aggregations of free-ranging sicklefin lemon sharks (Negaprion
      acutidens). Using a novel monitoring protocol, we analysed both dominance
      interactions and tolerance associations between sharks competing for food in
      relation with the number, the morphology and the behaviour of rivals. Sharks
      produced more agonistic displays and spent more time around the bait as
      competitors were more abundant. Moreover, the morphological attributes of
      competitors had very limited influence on the structure of shark social
      interactions. Instead, sharks appeared to establish tolerance relationships with
      competitors according to their individual behaviour. Furthermore, the more two
      sharks were observed together at a given study site, the fewer agonistic
      interactions they exchanged. We discuss these findings as evidence of the use of
      social cues in a non-gregarious predatory species and suggest directions for
      future research.

PMID- 29593112
TI  - Specific adaptation to strong competitors can offset the negative effects of
      population size reductions.
AB  - Competition plays a crucial role in determining adaptation of species, yet we
      know little as to how adaptation is affected by the strength of competition. On
      the one hand, strong competition typically results in population size reductions,
      which can hamper adaptation owing to a shortage of beneficial mutations; on the
      other hand, specificity of adaptation to competitors may offset the negative
      evolutionary consequences of such population size effects. Here, we investigate
      how competition strength affects population fitness in the bacterium Pseudomonas
      fluorescens Our results demonstrate that strong competition constrains adaptation
      of focal populations, which can be partially explained by population size
      reductions. However, fitness assays also reveal specific adaptation of focal
      populations to particular competitors varying in competitive ability.
      Additionally, this specific adaptation can offset the negative effects of
      competitor-mediated population size reductions under strong competition. Our
      study, therefore, highlights the importance of opposing effects of strong
      competition on species adaptation, which may lead to different outcomes of
      colonization under intense and relaxed competitive environments in the context of
      population dispersal.

PMID- 29593113
TI  - Indirect evolution of social fitness inequalities and facultative social
      exploitation.
AB  - Microbial genotypes with similarly high proficiency at a cooperative behaviour in
      genetically pure groups often exhibit fitness inequalities caused by social
      interaction in mixed groups. Winning competitors in this scenario have been
      referred to as 'cheaters' in some studies. Such interaction-specific fitness
      inequalities, as well as social exploitation (in which interaction between
      genotypes increases absolute fitness), might evolve due to selection for
      competitiveness at the focal behaviour or might arise non-adaptively due to
      pleiotropy, hitchhiking or genetic drift. The bacterium Myxococcus xanthus
      sporulates during cooperative development of multicellular fruiting bodies. Using
      M. xanthus lineages that underwent experimental evolution in allopatry without
      selection on sporulation, we demonstrate that interaction-specific fitness
      inequalities and facultative social exploitation during development readily
      evolved indirectly among descendant lineages. Fitness inequalities between
      evolved genotypes were not caused by divergence in developmental speed, as faster
      developing strains were not over-represented among competition winners. In
      competitions between ancestors and several evolved strains, all evolved genotypes
      produced more spores than the ancestors, including losers of evolved-versus
      evolved competitions, indicating that adaptation in non-developmental contexts
      pleiotropically increased competitiveness for spore production. Overall, our
      results suggest that fitness inequalities caused by social interaction during
      cooperative processes may often evolve non-adaptively in natural populations.

PMID- 29593114
TI  - Does observability affect prosociality?
AB  - The observation of behaviour is a key theoretical parameter underlying a number
      of models of prosociality. However, the empirical findings showing the effect of
      observability on prosociality are mixed. In this meta-analysis, we explore the
      boundary conditions that may account for this variability, by exploring key
      theoretical and methodological moderators of this link. We identified 117 papers
      yielding 134 study level effects (total n = 788 164) and found a small but
      statistically significant, positive association between observability and
      prosociality (r = 0.141, 95% confidence interval = 0.106, 0.175). Moderator
      analysis showed that observability produced stronger effects on prosociality: (i)
      in the presence of passive observers (i.e. people whose role was to only observe
      participants) versus perceptions of being watched, (ii) when participants'
      decisions were consequential (versus non-consequential), (iii) when the studies
      were performed in the laboratory (as opposed to in the field/online), (iv) when
      the studies used repeated measures (instead of single games), and (v) when the
      studies involved social dilemmas (instead of bargaining games). These effects
      show the conditions under which observability effects on prosociality will be
      maximally observed. We describe the theoretical and practical significance of
      these results.

PMID- 29593115
TI  - Do detour tasks provide accurate assays of inhibitory control?
AB  - Transparent Cylinder and Barrier tasks are used to purportedly assess inhibitory
      control in a variety of animals. However, we suspect that performances on these
      detour tasks are influenced by non-cognitive traits, which may result in
      inaccurate assays of inhibitory control. We therefore reared pheasants under
      standardized conditions and presented each bird with two sets of similar tasks
      commonly used to measure inhibitory control. We recorded the number of times
      subjects incorrectly attempted to access a reward through transparent barriers,
      and their latencies to solve each task. Such measures are commonly used to infer
      the differential expression of inhibitory control. We found little evidence that
      their performances were consistent across the two different Putative Inhibitory
      Control Tasks (PICTs). Improvements in performance across trials showed that
      pheasants learned the affordances of each specific task. Critically, prior
      experience of transparent tasks, either Barrier or Cylinder, also improved
      subsequent inhibitory control performance on a novel task, suggesting that they
      also learned the general properties of transparent obstacles. Individual measures
      of persistence, assayed in a third task, were positively related to their
      frequency of incorrect attempts to solve the transparent inhibitory control
      tasks. Neophobia, Sex and Body Condition had no influence on individual
      performance. Contrary to previous studies of primates, pheasants with poor
      performance on PICTs had a wider dietary breadth assayed using a free-choice
      task. Our results demonstrate that in systems or taxa where prior experience and
      differences in development cannot be accounted for, individual differences in
      performance on commonly used detour-dependent PICTS may reveal more about an
      individual's prior experience of transparent objects, or their motivation to
      acquire food, than providing a reliable measure of their inhibitory control.

PMID- 29593116
TI  - TGFbeta-facilitated optic fissure fusion and the role of bone morphogenetic
      protein antagonism.
AB  - The optic fissure is a transient gap in the developing vertebrate eye, which must
      be closed as development proceeds. A persisting optic fissure, coloboma, is a
      major cause for blindness in children. Although many genes have been linked to
      coloboma, the process of optic fissure fusion is still little appreciated,
      especially on a molecular level. We identified a coloboma in mice with a targeted
      inactivation of transforming growth factor beta2 (TGFbeta2). Notably, here the
      optic fissure margins must have touched, however failed to fuse. Transcriptomic
      analyses indicated an effect on remodelling of the extracellular matrix (ECM) as
      an underlying mechanism. TGFbeta signalling is well known for its effect on ECM
      remodelling, but it is at the same time often inhibited by bone morphogenetic
      protein (BMP) signalling. Notably, we also identified two BMP antagonists among
      the downregulated genes. For further functional analyses we made use of
      zebrafish, in which we found TGFbeta ligands expressed in the developing eye, and
      the ligand binding receptor in the optic fissure margins where we also found
      active TGFbeta signalling and, notably, also gremlin 2b (grem2b) and follistatin
      a (fsta), homologues of the regulated BMP antagonists. We hypothesized that
      TGFbeta is locally inducing expression of BMP antagonists within the margins to
      relieve the inhibition from its regulatory capacity regarding ECM remodelling. We
      tested our hypothesis and found that induced BMP expression is sufficient to
      inhibit optic fissure fusion, resulting in coloboma. Our findings can likely be
      applied also to other fusion processes, especially when TGFbeta signalling or BMP
      antagonism is involved, as in fusion processes during orofacial development.

PMID- 29593117
TI  - Genetic defects in SAPK signalling, chromatin regulation, vesicle transport and
      CoA-related lipid metabolism are rescued by rapamycin in fission yeast.
AB  - Rapamycin inhibits TOR (target of rapamycin) kinase, and is being used clinically
      to treat various diseases ranging from cancers to fibrodysplasia ossificans
      progressiva. To understand rapamycin mechanisms of action more comprehensively,
      1014 temperature-sensitive (ts) fission yeast (Schizosaccharomyces pombe) mutants
      were screened in order to isolate strains in which the ts phenotype was rescued
      by rapamycin. Rapamycin-rescued 45 strains, among which 12 genes responsible for
      temperature sensitivity were identified. These genes are involved in stress
      activated protein kinase (SAPK) signalling, chromatin regulation, vesicle
      transport, and CoA- and mevalonate-related lipid metabolism. Subsequent
      metabolome analyses revealed that rapamycin upregulated stress-responsive
      metabolites, while it downregulated purine biosynthesis intermediates and
      nucleotide derivatives. Rapamycin alleviated abnormalities in cell growth and
      cell division caused by sty1 mutants (Deltasty1) of SAPK. Notably, in Deltasty1,
      rapamycin reduced greater than 75% of overproduced metabolites (greater than 2*
      WT), like purine biosynthesis intermediates and nucleotide derivatives, to WT
      levels. This suggests that these compounds may be the points at which the
      SAPK/TOR balance regulates continuous cell proliferation. Rapamycin might be
      therapeutically useful for specific defects of these gene functions.

PMID- 29593118
TI  - Entering the post-epigenomic age: back to epigenetics.
AB  - It is undeniably one of the greatest findings in biology that (with some very
      minor exceptions) every cell in the body possesses the whole genetic information
      needed to generate a complete individual. Today, this concept has been so
      thoroughly assimilated that we struggle to still see how surprising this finding
      actually was: all cellular phenotypes naturally occurring in one person are
      generated from genetic uniformity, and thus are per definition epigenetic.
      Transcriptional mechanisms are clearly critical for developing and protecting
      cell identities, because a mis-expression of few or even single genes can
      efficiently induce inappropriate cellular programmes. However, how
      transcriptional activities are molecularly controlled and which of the many known
      epigenomic features have causal roles remains unclear. Today, clarification of
      this issue is more pressing than ever because profiling efforts and epigenome
      wide association studies (EWAS) continuously provide comprehensive datasets
      depicting epigenomic differences between tissues and disease states. In this
      commentary, we propagate the idea of a widespread follow-up use of epigenome
      editing technology in EWAS studies. This would enable them to address the
      questions of which features, where in the genome, and which circumstances are
      essential to shape development and trigger disease states.

PMID- 29593120
TI  - ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced
      apoptosis and mitotic arrest in AGS human gastric cancer cells.
AB  - In this study, we investigated the role of AMP-activated protein kinase (AMPK)
      and the importance of reactive oxygen species (ROS) in apoptosis induction
      associated with cell cycle arrest induced by sulforaphane in AGS human gastric
      cancer cells. Our results demonstrated that sulforaphane inhibited proliferation
      of AGS cells by promoting apoptosis and accumulating the cellular portion of the
      G2/M phase via the buildup of cyclin B1 and cyclin-dependent kinase p21
      (WAF1/CIP1). Moreover, the phosphorylation of histone H3 was markedly increased
      following treatment with sulforaphane, indicating that sulforaphane stimulated
      mitotic arrest. Sulforaphane concurrently induced phosphorylation of AMPK;
      however, compound C, an AMPK inhibitor, significantly blocked sulforaphane
      induced apoptosis, suggesting that sulforaphane induces apoptosis of AGS cells
      through the AMPK-dependent pathway. Sulforaphane also activated the mitochondrial
      apoptotic signaling pathway with a decrease in mitochondrial membrane potential
      and the nuclear translocation of cytochrome c. Furthermore, sulforaphane provoked
      the generation of intracellular ROS; especially when ROS production was blocked
      by antioxidant N-acetylcysteine, both AMPK activation and growth inhibition by
      sulforaphane were completely abolished. Collectively, these findings suggest that
      sulforaphane inhibited growth of AGS cells, which was mediated by a complex
      interplay between cellular mechanisms governing redox homeostasis, apoptosis, and
      cell cycle arrest through an ROS/AMPK-dependent pathway.

PMID- 29593119
TI  - Analysis of the binding mode of a novel HIF1alpha inhibitor through molecular
      modelling.
AB  - Hypoxia inducible factor-1 (HIF1) is an important transcription factor related
      with tumor metastasis. As a subunit of HIF1, HIF1alpha plays an important role in
      regulation of the hypoxic response. HIF1alpha inhibitor could be a promising
      treatment for certain cancers. In the present study, we try to model the binding
      mode of the recent reported new series of HIF1alpha inhibitors with the purpose
      of further improving the performance of these inhibitors. Molecular docking was
      first employed to predict the binding modes of the protein-ligand complexes,
      followed by molecular dynamics simulations and MMGBSA free energy calculations.
      According to the predicted binding modes, these molecules form two important
      hydrogen bonds with HIF1alpha. Moreover, if the molecules could form a stable pi
      pi interaction with HIF1alpha, the potency of the inhibitors can be greatly
      improved. Hydrophobic interactions between the molecules and HIF1alpha are also a
      key factor, especially the interactions between the hydrophobic groups
      (benzimidazole) of the molecules and the hydrophobic residues inside the binding
      cave. Molecular modeling could be a useful method in the future drug design. In
      this study, our calculation can help to design and develop high potent HIF1alpha
      inhibitors in future.

PMID- 29593121
TI  - Proteomic analysis of human glutathione transferase omega (hGSTO1) stable
      transfection in a 6-hydroxydopamine-induced neuronal cells.
AB  - Parkinson's disease is the second most common neurodegenerative disorder after
      Alzheimer's disease. The disease is associated with dopaminergic neuron losses in
      the substantia nigra area of the brain and the formation of cytoplasmic inclusion
      bodies. Human glutathione transferase omega 1 (hGSTO1) appears to have a role in
      modulating stress response. The study was aimed to elucidate differentially
      expressed proteins caused by oxidative stress induced by 6-hydroxydopamine (6
      OHDA). Human neuronal cells SH-SY5Y overexpressing hGSTO1 were used to
      investigate protein glutathionylation and the modulation of cellular protein
      expression. Therefore SH-SY5Y/hGSTO1 and SH-SY5Y/control lysate proteins were
      separated by 2D-gel electrophoresis compared with untreated conditions in both
      standard and non-reducing conditions. In standard conditions, the analysis of
      protein profiles demonstrated 25 differentially expressed spots and 10 spots were
      chosen for further protein identification by LC-MS analysis. Several proteins
      were later identified as vimentin, galectin-1, high mobility group protein B2,
      clathrin, tropomyosin, heterogenous nuclear ribonucleoprotein and peroxiredoxin
      2. Search Tool for Interactions of Chemicals (STITCH) analysis suggested that
      oxidative stress induced by 6-OHDA involved carbohydrate metabolism in SH-SY5Y
      via a lactose metabolic pathway. Our results raise the possibility that hGSTO1
      modulates the functions of many proteins that play a role in the degenerative
      cell response of a Parkinson's model.

PMID- 29593122
TI  - Inhibition of AT1 receptors by losartan affects myocardial slow force response in
      healthy but not in monocrotaline-treated young rats.
AB  - The slow force response (SFR) of a cardiac muscle to a sudden stretch is thought
      to be important in the regulatory adaptation of myocardial contraction. Autocrine
      paracrine regulation pathways which involve angiotensin II are participating in
      this mechanism. On the other hand, renin-angiotensin-aldosterone system (RAS) is
      altered in hypertrophic or failing myocardium. We compared the effects of sudden
      stretch to SFR as well as to twitch and Ca2+ transient characteristics in rat
      myocardium with monocrotaline-induced heart failure with those in normal rat
      myocardium without and with inhibition of angiotensin II type-1 (AT1) receptors.
      Our findings indicate that the myocardium of rats with monocrotaline-induced
      right ventricular failure is deficient with activation of local RAS and therefore
      expresses blunted SFR, very similar to the depression of SFR observed in normal
      myocardium under inhibition of AT1 receptors. The "failing" myocardium does not
      further respond to the "putative" inhibition of AT1 receptors by losartan. In
      conclusion, SFR is related to autocrine-paracrine regulation of myocardial
      contraction in normal rat myocardium and that the involvement of RAS into stretch
      induced modulation of contractility may be significantly altered in failing
      heart.

PMID- 29593123
TI  - Toxicogenomic evaluation of liver responses induced by acrylamide and glycidamide
      in male mouse liver.
AB  - In current studies, histopathologic method, Agilent GeneChip hybridization and
      Western blot were used to investigate the toxicity of acrylamide (AA) and
      glycidamide (GA) in male mouse livers. The histopathologic results demonstrated
      that AA and GA could cause oxidative damage to mouse liver. Middle dose of GA and
      AA (50 mg/kg b.w./day) could significantly up-regulate the expression of
      cytochrome P450, as well as genes related to oxidative injury, cancer and
      inflammation, and significantly down-regulate the expression of genes related to
      anti-apoptosis, antioncogene and fatty acid synthesis. Middle and high dose (75
      mg/kg b.w./day) of GA and AA could both down-regulate the expression of hepatic
      anti-oncogene Bcl2 and up-regulate the expression of cancer-related gene Rad51
      and EGFR protein. The expression of anti-oncogene P21 induced by AA and GA was
      decreased. Our current study demonstrated that the oxidative damage, immune
      injury and carcinogenicity of mouse liver samples could be induced by AA and GA
      at histopathological, entire genome and protein levels.

PMID- 29593124
TI  - Association between 3'UTR polymorphisms in genes ACVR2A, AGTR1 and RGS2 and
      preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy specific disease with several risk factors such
      as genetic polymorphisms, environmental and social factors participating in its
      development. The aim of this study was to investigate whether distribution of
      three putative regulatory SNPs rs13430086, rs5186, rs4606 in 3'UTR of genes
      ACVR2A, AGTR1 and RGS2, respectively, that have been associated with hypertension
      and regulation of trophoblast invasion differ between women with PE and control
      group. The associations of rs13430086, rs5186 and rs4606 with preeclampsia were
      tested in two groups - the group of 50 women with PE and the control group of 42
      healthy pregnant women at term. DNA was isolated from blood samples and the
      determination of genotypes was performed using Real-Time PCR. Power analysis for
      the size of the cohort was performed and the results were analyzed using Fisher
      exact test. The AA genotype of ACVR2A rs13430086 was significantly associated
      with higher risk to preeclampsia compared with TT genotype (p = 0.026, OR: 5.39,
      95%CI: 1.21-31.54). Results showed no association between genotypes and
      preeclampsia for polymorphisms rs5186, rs4606. Further studies are important in
      order to better understand the role of ACVR2A in the pathogenesis of PE.

PMID- 29593125
TI  - Upregulation of heme oxygenase 1 (HO-1) attenuates kidney damage, oxidative
      stress and inflammatory reaction during renal ischemia/ reperfusion injury.
AB  - The current study investigated the effect of upregulation of heme oxygenase 1 (HO
      1) by cobalt protoporphyrin (CoPP) on renal dysfunctions in renal
      ischemia/reperfusion (I/R) injury and its underlying mechanisms. 72 male Sprague
      Dawley rats were divided into 4 groups: sham group, ischemic group (left 45-min
      renal ischemia), CoPP-before group (as ischemic group with CoPP 20 mg/kg 30 min
      before ischemia) and CoPP-after group (as ischemic group with CoPP 20 mg/kg 20
      min after ischemia). Serum creatinine, urea and TGF-beta1 and markers of redox
      state (MDA, SOD, GSH and CAT), nitric oxide (NO), TGF-beta1 and HO-1 in kidney
      tissues were measured. Serum creatinine and urea levels were significantly
      increased in ischemic group and attenuated in CoPP-treated groups (p < 0.05).
      Also, markers of redox state showed significant deteriorations in ischemic group
      which were improved significantly in CoPP-treated groups (p < 0.05). HO-1
      expression in kidney tissues showed significant increase in ischemic group and
      showed more significant increase in CoPP-treated groups (p < 0.05). Moreover,
      serum and renal TGF-beta1 levels were significantly increased in ischemic group
      and attenuated in CoPP-treated groups (p ? 0.05). We concluded that up-regulation
      of HO-1 by CoPP treatment before and after renal I/R injury improved the kidney
      function and morphology and this might be due to impairment of oxidative stress
      and inflammatory cytokines in kidney tissues.

PMID- 29593126
TI  - Effect of the allopregnanolone and allotetrahydrodeoxycorticosteron on spike-wave
      discharges in the EEG of absence epilepsy rat models.
AB  - Absence epilepsy is a generalized nonconvulsive type of epilepsy that is
      characterized by spike-wave discharges (SWD) with a frequency of 2.5-4 Hz in the
      EEG. The activation of the GABAergic system in central nervous system suppresses
      convulsive seizures but exacerbates absence seizures. Endogenous neuroactive
      steroids such as 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THPROG;
      allopregnanolone) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha
      THDOC, allotetrahydrodeoxycorticosteron) are GABA-A receptor-positive allosteric
      modulators. Finasteride which is a 5alpha-reductase inhibitor can selectively
      block the synthesis of endogenous steroids. In this study, we compared the
      effects of endogenous steroids (THPROG and THDOC) on SWD by using finasteride
      treated Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats as a model of absence
      epilepsy. Wistar (WIS-THPROG and WIS-THDOC) and WAG/Rij (WAG-THPROG and WAG
      THDOC) rats were divided into 4 groups (n = 8). After stereotactic surgical
      procedures, all rats were prepared for direct cortical EEG measurement. Following
      finasteride administration to each group, THPROG was administered to WIS-THPROG
      and WAG-THPROG groups, and THDOC to WIS-THDOC and WAG-THDOC groups
      intraperitoneally. While there was no any SWD activity detected in WIS-THPROG and
      WIS-THDOC groups, a significant increase in SWD count in WAG-THPROG (p = 0.012)
      and in WAG-THDOC (p = 0.012), and in SWD total duration in WAG-THPROG (p = 0.012)
      and WAG-THDOC groups (p = 0.011) were observed after steroid injection. No
      difference between the efficacy of THPROG and THDOC on absence seizures in
      WAG/Rij rats was observed.

PMID- 29593127
TI  - Sulfamethoxazole induces zinc changes at hippocampal mossy fiber synapses from
      pregnant rats.
AB  - The accumulation of intracellular ionic zinc and pharmaceutical compounds, like
      the antibiotic sulfamethoxazole, may contribute to various neuropathologies.
      Sulfamethoxazole and the drug trimethoprim, are inhibitors of enzymes involved in
      the synthesis of tetrahydrofolate and also of carbonic anhydrases. The inhibition
      of the latter enzymes, which are localized both intra- and extracellularly and
      have a key role in pH regulation, causes alkalinization that is associated with
      higher spontaneous transmitter release. Intense synaptic stimulation causes the
      entry of released zinc into postsynaptic neurons, through glutamate receptor
      channels or voltage dependent calcium channels. The aim of this study was to
      evaluate the effect of sulfamethoxazole (180 MUM) on basal postsynaptic zinc and
      to compare it with that caused by two depolarizing media, containing high
      potassium or tetraethylammonium, which may induce long term synaptic plasticity.
      The studies were performed in brain slices from gestating rats, at the mossy
      fiber synapses from hippocampal CA3 area, using the zinc indicator Newport Green.
      In the presence of KCl (20 mM) and sulfamethoxazole (180 MUM) the zinc signals
      were enhanced, unlike in tetraethylammonium (25 mM). After sulfamethoxazole the
      tetraethylammonium evoked zinc signal had reduced amplitude. Thus, the data
      suggests that sulfamethoxazole enhances transmitter release affecting synaptic
      zinc physiology.

PMID- 29593128
TI  - Selective inhibition of smooth muscle plasma membrane transport Sa2+,Mg2+-ATRase
      by calixarene C-90 and its activation by IPT-35 compound.
AB  - We investigated the influence of calixarene C-90 and IPT-35 on plasma membrane
      Ca2+- pumping ATRase (PMCA), intracellular calcium homeostasis and myometrium
      smooth muscle strain contractions. It has been shown that both effectors (100
      MUM) affect PMCA enzymatic activity: calixarene C-90 inhibits it by 75% and IPT
      35 activates it by 40%. These compounds don't affect the Mg2+-ATRase, Mg2+
      independent Sa2+-ATRase and Na+,K+-ATRase enzymatic activities. C-90 inhibition
      coefficient I0.5 magnitude was approximately 20 MUM and the Hill coefficient nH
      was 0.55. For IPT-35 activation, constant A0.5 was 6.4 and nH was 0.7.
      Mathematical modeling demonstrated the implication of calixarene C-90 on
      unexcited myocytes, which allows for a precise change in cytoplasm Ca2+
      concentration and an influence on basal muscle tonus. By the same method, we
      determined that IPT-35 has a little influence on Ca2+ concentration in unexcited
      myocytes. It was also shown that calixarene C-90 in vitro can increase velocity
      of oxytocin-initiated contractions, whereas IPT-35 can suppress this
      aforementioned parameter. These results are promising for the design of new
      pharmacological compounds as better regulators of uterine contractions.
      Calixarene C-90 can be used in obstetric cases for the simultaneous use of
      oxytocin for enhancing uterine contractions, and IPT-35 for its antispasmodic
      effect on uterine tone.

PMID- 29593129
TI  - Novel neuroprotective role of hydrogen sulfide in a rat model of stress brain
      injury.
AB  - Hydrogen sulfide (H2S) is a gaseous mediator recognized as important
      neuromodulator agent in the central nervous system. Since stress is among the
      most important factors involved in several pathophysiological brain processes.
      This study aim to investigate the effect of exogenous H2S on the possible
      negative effect of stress on the brain of rats and the underlying mechanisms.
      Rats were divided into 3 groups: control, stressed, H2S treated + stress. Brain
      injury markers measured were serum S100 protein and gamma enolase. Stress leads
      to obvious detrimental effects on the brain tissues; it produced significant
      increase in serum level of the above mentioned brain injury markers, and
      significant increase in brain levels of nitric oxide (NO), tumor necrosis factor
      alpha (TNFalpha), and malondialdehyde (MDA) the lipid peroxidation degradative
      product along with significant decrease in brain glutathione level. H2S pre
      treatment before stress application abolished the above detrimental effects of
      stress on the brain tissue since it produced significant decreases in the
      stressinduced expression of brain injury markers, brain TNFalpha, brain NO and
      brain MDA, and significant increases in the stress-induced reduction of brain
      glutathione. H2S has significant neuroprotective role in the nervous system
      against stress-induced significant brain injury through its antioxidant and anti
      inflammatory effects.

PMID- 29593130
TI  - Nonhuman primate breath volatile organic compounds associate with developmental
      programming and cardio-metabolic status.
AB  - Rodent and nonhuman primate studies indicate that developmental programming by
      reduced perinatal nutrition negatively impacts life course cardio-metabolic
      health. We have developed a baboon model in which we feed control mothers (CON)
      ad libitum while nutrient restricted mothers are fed 70% of ad libitum global
      feed in pregnancy and lactation. Offspring of nutrient restricted mothers are
      intrauterine growth restricted (IUGR) at term. By 3.5 years IUGR baboons showed
      signs of insulin resistance, indicating a pre-diabetic phenotype, in contrast to
      healthy CON offspring. We hypothesized that a novel breath analysis approach
      would provide markers of the altered cardio-metabolic state in a non-invasive
      manner. Here we assess whether exhaled breath volatile organic compounds (VOCs)
      collected from this unique cohort of juvenile baboons with documented cardio
      metabolic dysfunction resulting from in utero programming can be detected from
      their breath signatures. Breath was collected from male and female CON and IUGR
      baboons at 4.8 +/- 0.2 years (human equivalent ~13 years). Breath VOCs were
      quantified using a two-dimensional gas chromatography mass spectrometer. Two-way
      ANOVA, on 76 biologically relevant VOCs identified 27 VOCs (p < 0.05) with
      altered abundances between groups (sex, birthweight, and sex x birthweight). The
      27 VOCs included 2-pentanone, 2-octanone, 2,2,7,7-tetramethyloctane and 3-methyl
      1-heptene, which have not previously been associated with cardio-metabolic
      disease. Unsupervised principal component analysis of these VOCs could
      discriminate the four clusters defining males, females, CON and IUGR. This study,
      which is the first to assess quantifiable breath signatures associated with
      cardio-metabolic programing for any model of IUGR, demonstrates the translational
      value of this unique model to identify metabolites of programmed cardio-metabolic
      dysfunction in breath signatures. Future studies are required to validate the
      translatability of these findings to humans.

PMID- 29593131
TI  - [Milk, Daily products and Bone health.Effect of milks and daily products on bone
      health.]
AB  - In Japan, nutrition education programs to prevent osteoporosis and osteoporotic
      fractures have focused primarily on increasing dietary calcium intake and
      recommended the consumption of milk and dairy products. However, the effect of
      milk and dairy product consumption on bone density loss or fracture incidence in
      Japanese has rarely been evaluated in randomized controlled studies. In the
      present study, we reviewed the literature investigating the consumption of milk
      and dairy products in relation to bone density and fracture risk. The results
      showed that milk and dairy product consumption had only a modest effect in the
      prevention of midlife bone loss and subsequent fractures. However, given that
      infrequent(once weekly or less)consumption of milk may be associated with an
      increased risk of femoral neck fracture, and that Japanese generally have a lower
      calcium intake, it is still necessary to encourage elderly and younger adults to
      increase their consumption of milk and dairy products to promote bone health.

PMID- 29593132
TI  - [Milk, Daily products and Bone health.Milk or dairy products and
      bone:Epidemiology.]
AB  - An assessment of the association between the intake of milk or dairy products and
      bone density or the risk of fractures on the basis of epidemiological studies
      revealed the following findings:(1)a sufficient prepubertal intake of milk or
      dairy products could contribute to the increased bone growth and maximized peal
      bone mass because the intake of calcium in the corresponding stage in Japan is
      inadequate;(2)adequate milk intake could contribute to the maintenance of peal
      bone mass among menstruating adult females and the decrease of bone loss in
      postmenopausal females. Adequate milk intake could contribute to the decrease of
      aging-induced bone loss in elderly males, though there is no sufficient
      scientific evidence;and(3)a meta-analysis indicated no correlation between the
      increased milk intake and decreased risks of hip fractures in the elderly. As the
      intake of milk or dairy products in the Japanese elderly is rather less than that
      reported by the meta-analysis, the minimal intake of milk or dairy products is
      anticipated to elevate the risk of fractures in middle-aged or elderly males and
      females although the scientific evidence is inadequate.

PMID- 29593133
TI  - [Milk, Daily products and Bone health.Milk, Daily products and Bone
      health.Dietary Reference Intakes of Calcium by age group.]
AB  - The amount of calcium in the body changes with age. According to the Dietary
      Reference Intakes for Japanese(2015), the required amount of calcium is
      calculated by a factor addition method in consideration of the amount of calcium
      accumulated in the body, the amount excreted in urine, and percutaneous losses.
      At that time, the calcium absorption rate becomes a very important factor.
      Numerical values are set so as to increase the amount of calcium in the body
      during the growth phase in order to maintain the calcium content in the body
      after adulthood. Based on the available evidence, the calcium intake level of
      Japanese is low and needs to be increased.

PMID- 29593134
TI  - [Milk, Daily products and Bone health.Nutritional Value of Milk and Dairy
      Products.]
AB  - Milk has been historically recognized as having great nutritional value;its high
      nutrient density per energy makes it useful for individuals recovering from
      malnutrition among others. Milk is composed of an excellent ratio of essential
      amino acids, with an amino acid score of 100, and enhances the protein content
      when served with a meal. Additionally, not only is milk rich in calcium, but the
      absorption rate of calcium contained in the meal increases when milk is served
      with a meal. Instead of consuming nutritional supplements to make up for a lack
      of nutrients in the diet, Milk is a representative food that highlights the
      nutritional value of taking one food in combination with other foods. Moreover,
      milk costing as little as 100 contains high nutrient density, making it an
      economically efficient food.

PMID- 29593135
TI  - [Milk, Daily products and Bone health.Characteristics of calcium in milk.]
AB  - Milk contains approximately 110mg of calcium per 100mL of milk, a good source of
      dietary calcium. The calcium in milk comprises of calcium caseinate, micellar
      calcium phosphate and soluble calcium. It is also reported that the calcium in
      milk has an excellent bioavailability. Intervention studies of Japanese women
      have shown that the absorption rate of calcium in milk was greater than that
      found in small fish and vegetables. Factors taken into account as contributing to
      higher absorption rates of calcium in milk were:1)the types of calcium
      present(caseinate, micellar, soluble), 2)the presence of lactose which promotes
      calcium absorption, and 3)the presence of casein-phosphopeptide which increases
      soluble calcium fraction. Higher solubility was also observed in the small
      intestine of rats fed a micellar calcium phosphate casein-phosphopeptide(MCP
      CPP)complex prepared from milk compared to that in rats fed insoluble whey
      calcium.

PMID- 29593136
TI  - [Milk, Daily products and Bone health.Effect of Milk or Milk Protein on Cognitive
      Function.]
AB  - Increase in milk and dairy intake reduces the development of all-cause dementia,
      especially Alzheimer's disease(AD)in elderly Japanese population from the
      Hisayama study. Recent meta-analysis also indicates that beneficial effect of
      milk and dairy intake on cognitive disorders is significantly observed in Asian
      population. We have reported that oral administration of milk peptide, CH-3 to AD
      model mice not only improved cognitive function but also suppressed the
      expression of inflammatory cytokines and production of oxidative stress.
      Moreover, administration of other milk proteins improves cognitive function or
      outcome in AD patients. These findings indicate that milk and dairy intake have
      possible anti-dementia effects. Further analysis should be necessary to overcome
      the explosion of dementia worldwide with lifestyle modification.

PMID- 29593137
TI  - [Milk, Daily products and Bone health.Milk and Dairy Products and "Wasyoku" -"New
      wasyoku"-.]
AB  - "Wasyoku;the traditional diets of Japan" refers to foods generally consumed by
      Japanese people, which is in contrast with the Western diets introduced by
      Europeans and Americans. The basic Japanese dietary pattern consists of rice as a
      staple food combined with one soup and two side dishes in a meal, making it
      easier to achieve a balanced nutritional status. However, salt content tends to
      be high in "Wasyoku", which negatively affects the overall health of an
      individual. Recently, Japanese's salt intake has been slowly decreasing;however,
      a further reduction by approximately 2 g per day is required to prevent
      hypertension and cardiovascular diseases. To reduce salt intake, while keeping a
      balanced nutritional status and obtaining adequate amount of energy and
      nutrients, one should be used to consume a lightly flavored food. However, as
      Japanese individuals have been accustomed to a high salt diet, which is directly
      related to a person's good taste or satisfaction level, shifting to lightly
      flavored foods is extremely difficult. Therefore, one of the methods developed to
      reduce salt intake is a "New Wasyoku;milk-plus traditional diets of Japan," a
      recipe utilizing the "koku" or umami taste of milk. The "New Wasyoku" is
      characterized by adopting to a milk/dairy product-based recipe, which promotes
      the realization of natural, healthy diets, while maintaining the palatability and
      nutritional balance of diets.

PMID- 29593138
TI  - [Milk, Daily products and Bone health.The effect of lactulose on bone health.]
AB  - Lactulose is a non-digestible oligosaccharide, consisting of galactose and
      fructose. Bifidobacteria in the large intestine assimilate and metabolize
      lactulose, which has not been degraded or absorbed by humans, and they
      subsequently proliferate. Predominant bifidobacteria release short chain fatty
      acids, such as acetic acid and lactic acid, into the intestinal tract by
      lactulose metabolization, which lowers the intraluminal pH. As a result, the
      calcium that has flowed into the large intestine without absorption in the small
      intestine is solubilized and absorbed in the large intestine. So that means
      continuous ingestion of lactulose might contribute to bone health by increasing
      the absorption efficiency of calcium.

PMID- 29593139
TI  - [Milk, Daily products and Bone health.Milk intake and Bone acquisition in junior
      high school and high school students.]
AB  - The junior high school and high school years are the periods during which
      development spurts occur, and bone mass increases including height and weight.
      The bone mass gain at this time has a big influence on the maximum bone mass,
      which also leads to prevention of future osteoporosis. Calcium intake is
      important for bone mass acquisition, but there is a divergence between the value
      indicated by the meal intake standard and the actual intake amount, and efforts
      to increase the calcium intake amount are necessary. From the results obtained by
      providing milk with school lunch, the significance of drinking milk as a source
      of calcium at this time is particularly large.

PMID- 29593140
TI  - [Milk, Daily products and Bone health.Effects of School Lunch Programs on Bone
      Mass.]
AB  - In Japan, school lunches are provided to elementary and secondary student, not
      only for ensuring the intake of well-balanced and nutritious meal, but also
      hoping to improve their dietary habits. In this article, the authors review the
      effects of a school lunch program on the bone mass and dietary habits. The school
      lunch program was divided into 3 groups:a group provided with a complete school
      lunch, a group provided with only milk supplements, and a group provided with no
      supplement. The calcaneal bone mass was significantly higher in both primary and
      the junior high-school students given complete lunches compared with that in the
      other groups. Moreover, the intake of milk and milk products besides school
      lunches was more frequent in the groups that received complete lunches. The
      results suggest that the school lunch program, particularly that providing
      complete lunches, contributed to increasing the bone mass and improving the
      dietary habits.

PMID- 29593141
TI  - [Milk, Daily products and Bone health.School lunch and calcium intake.]
AB  - The nutritional standard for calcium is set to 50%of the recommended dietary
      allowance because of the difficulty of obtaining it in the Japanese daily diet.
      Dairy products, vegetables and pulses were the main sources of calcium in school
      lunch. The consumption of calcium was significantly higher on the days with
      school lunches and at lunch. The consumption of calcium in the school lunch has
      changed the distribution of calcium intake upward, and decreased the number of
      estimated subjects that were below estimated average requirment.

PMID- 29593142
TI  - [Milk, Daily products and Bone health.MBPR and bone health.]
AB  - MBP is a complex of more than 100 basic proteins prepared from bovine milk. It
      was found that MBP improved the bone metabolism and there are many reports of in
      vitro studies using osteoblast and osteoclast, animal studies using osteoporosis
      model and human studies. In human study, oral administration of MBP modulate the
      balance of bone formation and resorption and improve bone mineral density
      regardless of age. Research on active component and safety of MBP has been
      conducted. MBP is used for the variety of commercial foods, such as dairy
      products, supplements and so on.

PMID- 29593143
TI  - [Optogenetic enhancement of everyday memory.]
AB  - Everyday memories are encoded in the hippocampus and decay very rapidly. In
      contrast, everyday memory with novel experience before or after remains for a
      long time. Our research group applied optogenetics to behavioural test in mice.
      We revealed the possibility that non-canonical release of dopamine from the locus
      coeruleus into the hippocampus change trivial everyday memory to long-term
      memory.

PMID- 29593144
TI  - Poor toe flexor strength, but not handgrip strength, is associated with the
      prevalence of diabetes mellitus in middle-aged males.
AB  - Previous studies suggested that reduced muscular strength was one of the
      potential predictor of prevalence of diabetes mellitus. The purpose of this study
      was to investigate the association between toe flexor strength (TFS) and handgrip
      strength (HGS) and the prevalence of diabetes mellitus. Cross-sectional analysis
      was conducted using data from 1,390 Japanese males (35-59 years). TFS and HGS
      were measured and medical examinations undertaken. The prevalence of diabetes
      mellitus was defined as fasting blood glucose >=126 mg/dL, glycated hemoglobin
      >=6.5% (48 mmol/mol), and/or current use of anti-diabetes mellitus drugs. A total
      of 114 participants had diabetes mellitus. TFS in participants with diabetes
      mellitus was significantly lower than that in persons not suffering from diabetes
      mellitus but HGS was not. Odds ratio (OR) and 95% confidence interval (CI) per 1
      standard deviation-increase in muscular strength measurements for the prevalence
      of diabetes mellitus were obtained using a multiple logistic regression model.
      Prevalence of diabetes mellitus was inversely related to TFS (OR 0.769, 95% CI
      0.614-0.963), TFS/body mass (BM) (0.696, 0.545-0.889) and TFS/body mass index
      (BMI) (0.690, 0.539-0.882) after adjustment of covariates. Such associations were
      not observed in HGS (OR 0.976, 95% CI 0.773-1.232), HGS/BM (0.868, 0.666-1.133)
      or HGS/BMI (0.826, 0.642-1.062). These results suggested that poor TFS was
      associated with an increased prevalence of diabetes mellitus independent of
      visceral fat accumulation, but HGS was not, in middle-aged males. TFS may be a
      better marker for the prevalence of diabetes mellitus than HGS.

PMID- 29593145
TI  - Routine Indwelling Urethral Catheterization in Acute Heart Failure Patients Is
      Associated With Increased Urinary Tract Complications Without Improved Heart
      Failure Outcomes.
AB  - BACKGROUND: Indwelling urethral catheters (IUC) are routinely inserted for the
      purpose of monitoring urine output in patients with acute heart failure (AHF).
      The benefit of IUC in patients capable of complying with urine collection
      protocols is unclear, and IUC carry multiple risks. This study describes the
      impact of IUC on AHF treatment.Methods and Results:A total of 540 records were
      retrospectively analyzed. After exclusion criteria were applied, 316 patients
      were propensity matched to establish groups of 100 AHF patients who either did
      (IUC(+)) or did not receive an IUC (IUC(-)) upon admission. Hospital length of
      stay (9 vs. 7 days), in-hospital urinary complications (24 vs. 5%), and 1-year
      urinary tract infection rate (17 vs. 6%; HR, 3.145; 95% CI: 1.240-7.978) were
      significantly higher in the IUC(+) group (P<0.05 for all). There were no
      differences in 30-day rehospitalization (6 vs. 6%; HR, 0.981; 95% CI: 0.318
      3.058; P=0.986) or major adverse cardiac/cerebrovascular events at 1 year (37 vs.
      32%, HR, 1.070; 95% CI: 0.636-1.799; P=0.798). CONCLUSIONS: Based on this
      retrospective analysis, the routine use of IUC may increase length of stay and
      UTI complications in AHF patients without reducing the risk for major
      cardiovascular and cerebrovascular events or 30-day rehospitalization rate.

PMID- 29593146
TI  - Sex Differences in Long-Term Clinical Outcomes in Patients With Atrial
      Fibrillation Undergoing Coronary Stent Implantation.
AB  - BACKGROUND: Patients with concomitant atrial fibrillation (AF) and coronary
      stenting are at high risk for both cardiovascular and bleeding events. We aimed
      to evaluate the influence of sex on long-term clinical outcomes in this patient
      subset.Methods and Results:We identified 1,450 patients with AF and coronary
      stenting in a patient-level pooled database from 3 Japanese studies, and compared
      3-year clinical outcomes between men and women (n=1,075, and n=375,
      respectively). The cumulative 3-year incidence of all-cause death was
      significantly higher in women than in men (26.5% vs. 17.2%, log-rank P<0.001),
      although after adjusting for confounders, the excess mortality risk of women
      relative to men was no longer significant (hazard ratio (HR): 1.12, 95%
      confidence interval (CI): 0.85-1.46, P=0.42). There were no significant
      differences in the adjusted 3-year risks for myocardial infarction or stroke
      between men and women (HR: 1.25, 95% CI: 0.62-2.40, P=0.52, and HR: 1.15, 95% CI:
      0.75-1.74, P=0.52, respectively). However, both the cumulative 3-year incidence
      of and adjusted risk for major bleeding were significantly higher in women than
      in men (17.0% vs. 11.3%, log-rank P=0.002, and HR: 1.47, 95% CI: 1.03-2.07,
      P=0.03). CONCLUSIONS: Among patients with concomitant AF and coronary stenting,
      there were no significant differences in the adjusted 3-year risks for all-cause
      death, myocardial infarction, and stroke between men and women. However, women as
      compared with men were associated with excess adjusted risk for major bleeding.

PMID- 29593148
TI  - [Rodent associated hantaviruses and hantavirus infections].
AB  - Hantaviruses belongs to the genus Hantavirus in the family Bunyaviridae are
      maintained in rodents and infects to humans by inhalation of the aerosol of
      infected rodent excreta. In this article, the epidemiology of hantavirus
      infection and the special relationship between rodent and hantavirus are
      described. Hantavirus infections include hemorrhagic fever with renal syndrome
      (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HFRS is characterized high
      fever, hemorrhage, and renal disorder. HFRS is distributed in East Asia, Europe,
      and Russia. While HCPS is characterized acute respiratory dysfunction and
      cardiogenic shock. The distribution of HCPS is limited in North and South
      Americas. In Japan's neighboring countries, such as Russia, China, and Korea,
      large numbers of HFRS patients are reported in association with multiple
      hantaviruses. In Japan, hantavirus infection has not been reported since 1985 but
      grey red-backed vole (Myodes rufocanus bedfordiae) inhabiting Hokkaido maintain
      one of the hantaviruses. Coevolution between hantavirus and host may have been
      occurred during a long period. The endemic areas of hantavirus infection are
      strongly associated with the distribution of host animal carrying pathogenic
      hantaviruses.

PMID- 29593147
TI  - [Current situation of measles in Japan, 2017].
AB  - A large-scale national measles epidemic occurred among mainly in teenagers and
      young adults in 2007. MHLW announced ''Special infectious disease prevention
      guidelines for measles'' (issued on 28 December 2007; Revised issued on 30 March
      2013), and Japan decided the elimination target year was fiscal year (FY) 2015.
      In 2008, it continued to be a large-scale nation epidemic exceeding 10,000 cases,
      and a large number of 0 to 1 year old infants, teenagers and young adults were
      suffering. Many cases were unvaccinated, single dose vaccination or unknown
      vaccination history. The number of measles cases has declined dramatically since
      2009, and the measles virus of genotype D5, which was the indigenous strain in
      Japan, was not detected at the end of May 2010. Regional epidemics were approved
      in 2011 and 2014, starting from imported cases from overseas, but it ended early.
      Since 2006, a two-dose routine vaccination regimen of measles rubella combined
      (MR) vaccine has started, moreover in the 5 years from fiscal 2008, the second
      dose of MR vaccine for junior high school students and high school students was
      periodically inoculated and immunization strengthened for teens was done. As a
      result, antibody positive rate of 95% or more is maintained in all age groups
      over 2 years old. In March 2015, Japan's measles elimination was certified by the
      WHO Western Pacific Regional Office. In 2017, outbreaks occurred in adults
      originating from imported cases from Asia or Europe, but early termination
      declarations have been made by aggressive measures by local public health
      centers/institutes. The annual number of reported cases after measles elimination
      certification is less than 200 cases.

PMID- 29593149
TI  - [Measles Virus].
AB  - Measles virus (MeV) is exceptionally contagious and still a major cause of death
      in child.However, recently significant progress towards the elimination of
      measles has been made through increased vaccination coverage of measles
      containing vaccines. The hemagglutinin (H) protein of MeV interacts with a
      cellular receptor, and this interaction is the first step of infection. MeV uses
      two different receptors, signaling lymphocyte activation molecule (SLAM) and
      nectin-4 expressed on immune cells and epithelial cells, respectively. The
      interactions of MeV with these receptors nicely explain the immune suppressive
      and high contagious properties of MeV. Binding of the H protein to a receptor
      triggers conformational changes in the fusion (F) protein, inducing fusion
      between viral and host plasma membranes for entry. The stalk region of the H
      protein plays a key role in the F protein-triggering. Recent studies of the H
      protein epitopes have revealed that the receptor binding site of the H protein
      constitutes a major neutralizing epitope. The interaction with two proteinaceous
      receptors probably imposes strong functional constraints on this epitope for
      amino acid changes. This would be a reason why measles vaccines, which are
      derived from MV strains isolated more than 60 years ago, are still highly
      effective against all MV strains currently circulating.

PMID- 29593150
TI  - [Social Responsibility of Virus Research].

PMID- 29593151
TI  - [Countermeasures against Plum pox virus in Japan.]

PMID- 29593152
TI  - [Emergence of emaraviruses, the eriophyoid mite-transmitted viruses in plants].
AB  - Members of the genus Emaravirus are plant viruses transmitted by eriophyoid
      mites. The emaravirus genome consists of multiple, negative-sense, single
      stranded RNA segments, that have been shown to be highly divergent. Recent
      studies have revealed that emaraviruses are associated with long-recognized
      diseases of world important crops such as fig mosaic disease or sterility mosaic
      disease of pigeon pea. Furthermore, along with the popularization of deep
      sequencing technologies, new putative members of emaraviruses have been reported
      year by year. This paper presents an overview of agricultural damages caused by
      emaraviruses worldwide and characteristics of their genomic RNAs and proteins. In
      addition, our research project to prevent a disease of a herb crop (shiso,
      Perilla frutescens) caused by Perilla mosaic virus, a putative emaravirus
      recently identified in Japan, is outlined.

PMID- 29593153
TI  - [Signal peptide peptidase participates in propagation and pathogenesis of
      hepatitis C virus].
AB  - Hepatitis C virus (HCV) is a blood-borne virus and causes chronic infection
      leading to development of steatosis, cirrhosis and hepatocellular carcinoma.
      However, molecular mechanisms of induction of liver diseases by HCV infection are
      still unclear. This review focuses on thevirological significance of processing
      of HCV core protein by signal peptide peptidase in propagation and pathogenesis
      of HCV.

PMID- 29593154
TI  - [Dynamics of the influenza virus genome regulated by cellular host factors].
AB  - For efficient replication of the influenza virus genome and its post
      replicational processes, not only viral factors but also host-derived cellular
      factors (host factors) are required. The influenza virus genome exists as viral
      ribonucleoprotein (vRNP) complexes with viral RNA-dependent RNA polymerases and
      nucleoprotein (NP). Using biochemical and proteomics approaches, we have
      identified host factors which are required for the vRNP replication and the
      progeny vRNP transport. We found that MCM complex, a cellular DNA replication
      licensing factor, is required for successful viral genome replication. In concert
      with the replication reaction, the nascent RNA chains are encapsidated with NP by
      cellular splicing factor UAP56. Further, after nuclear export of vRNP, we
      revealed that vRNP is transported to the plasma membrane using cholesterol
      enriched recycling endosomes through cell cycle-independent activation of the
      centrosome by YB-1, which is a mitotic centrosomal protein. Depletion of YB-1
      shows that the cholesterol-enriched endosomes are important for clustering of
      viral structural proteins at lipid rafts to assemble the virus particles
      concomitantly with the arrival of vRNP beneath the plasma membrane.

PMID- 29593155
TI  - [Molecular basis for negative-strand RNA virus entry and neutralization by
      antibodies].
AB  - Mononegaviruses are non-segmented negative-strand RNA viruses, and include
      measles, mumps, Marburg, and Ebola viruses. Measles virus and mumps virus,
      members of the family Paramyxoviridae, are immunotropic and neurotropic,
      respectively. Marburg virus and Ebola virus, members of the family Filoviridae,
      cause highly lethal hemorrhagic fever. In this paper, I summarize the recent
      structural and functional studies on the viral glycoproteins (GPs) of these
      viruses, which have shed light on virus entry and the humoral response. The
      structural and functional analyses of the interaction between viral GPs and
      receptors/antibodies also illuminate directions toward therapeutics against the
      viruses.

PMID- 29593160
TI  - Fracture force for veneered materials on restorations measured by torsion
      testing.
AB  - The torsional fracture strength at the interface between a base plate and
      veneering material was evaluated for three kinds of veneered restoration:
      porcelain fused to zirconia (PFZ), porcelain fused to metal (PFM), and composite
      resin veneered metal (CRVM). The metal and zirconia base plate (30*4*0.4 mm) were
      prepared and these plates were veneered as test specimens using each material to
      a total thickness of 1.2 mm. Torsional force was applied to each specimen using a
      rotational speed of 1.0 deg/min until the veneering material underwent fracture
      or exfoliation. The torsional fracture values were measured and the data were
      statistically analyzed using one-way ANOVA. The torsional fracture strength for
      PFZ, PFM, and CRVM was 3.0, 3.1, and 11.1 N*cm, respectively.

PMID- 29593161
TI  - Influence of restorative procedures on endodontically treated premolars: Finite
      element analysis of a CT-scan based three-dimensional model.
AB  - An endodontically treated tooth with mesial-occlusal-distal (MOD) cavity is often
      restored with composite resin. Palatal and buccal cusp reduction (MODP, MODPB),
      and/or fiber-reinforced composite posts (P), are used in an attempt to improve
      the longevity of the restoration. The aim of this study was to determine the
      effects of these procedures on von Mises stress values and distribution in dental
      tissues and restorative materials using finite element analysis. Based on CT
      scans of an extracted second upper premolar, six 3D endodontically treated tooth
      models (MOD, MODP, MODPB, MOD+P, MODP+P, MODPB+P) were created. Each model was
      subjected to a summary force of 150 N on the occlusal surface simulating the
      normal biting pattern and maximal von Mises stresses were calculated. MODP seems
      to reduce von Mises stress values in dental tissues and P seems to transfer some
      of the stresses from dental tissues to the composite filling.

PMID- 29593162
TI  - Influence of orthodontic self-etch adhesive on acid resistance of surface enamel.
AB  - The purpose of this study was to investigate the formation of acid-base resistant
      zone (ABRZ) of enamel surface during bracket bonding by using three self-etch
      adhesives presently available in the orthodontic treatment. Also, the relation
      between the thickness of the ABRZ and bonding strength, the relation between the
      thickness of the ABRZ and the concentration of fluoride ions contained in the
      adhesives, were discussed respectively. The ABRZ was formed with all self-etch
      orthodontic adhesives. ABRZ thicknesses of two self-etch adhesives were
      approximately 0.8-1.0 MUm, whereas ABRZ thickness of other one was about 0.1 MUm.
      The bond strengths of all self-etch orthodontic adhesives indicated over 10 MPa,
      and ABRZ thickness observed in the enamel surface seemed to have no influence to
      the bond strengths among self-etch adhesives. Moreover, the thickness of ABRZ
      appeared to be associated with the amount of fluoride ion released from the
      primer.

PMID- 29593163
TI  - In vitro evaluation of the cytotoxic activity of three epoxy resin-based
      endodontic sealers.
AB  - The aim of the study was to evaluate the cytotoxicity of three epoxy resin-based
      endodontic sealer, AH Plus, Sicura Seal and Top Seal. Direct and indirect
      cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay and LIVE/DEAD(r) Viability/Cytotoxicity Assay on MG63
      osteoblasts-like cells. Data were statistically analyzed by analysis of variance
      and Tukey test, setting a significance level of 5%. Both results related to
      direct and indirect cell viability tests showed that all groups were
      significantly more cytotoxic than the negative control group. The cytotoxicity
      activity after one week of culture showed the absence of direct cytotoxicity,
      while a medium rate of indirect cytotoxicity. All the three epoxy resin-based
      sealers (AH Plus, Top Seal and Sicura Seal) showed a medium rate of cytotoxicity
      on osteoblasts-like cells in vitro. No significant difference was found among the
      sealers analyzed.

PMID- 29593164
TI  - Effect of various dimethyl sulfoxide concentrations on the durability of dentin
      bonding and hybrid layer quality.
AB  - The objective was to evaluate effect of dimethyl sulfoxide (DMSO) on microtensile
      bond strength (uTBS) and nanoleakage (NL). Superficial dentin was acid-etched and
      pretreated with DMSO. Etch-and-rinse adhesive was applied and restored with resin
      composite incrementally. After 24 h, teeth were sectioned, stored in artificial
      saliva for 24-h or 6-months before uTBS evaluation. Failure modes were examined.
      Six beams per group were submitted to nanoleakage evaluation using SEM. Data were
      analyzed using ANOVA and Tukey's test (alpha=0.05). Pretreatment had no
      significant effect on uTBS after 24 h (p>0.05). After 6 months storage, uTBS of
      control decreased significantly, more than with the groups treated with 0.01% or
      higher (p<0.05). DMSO-pretreated groups preserved uTBS in all groups. After 6
      months, all groups except 0.001% showed significantly lower nanoleakege compared
      to control (p<0.05). DMSO (0.01-20%) may improve the hybrid layer integrity and
      bonding durability. The best results were seen with low (1-5%) of DMSO
      concentrations.

PMID- 29593166
TI  - Erratum.

PMID- 29593165
TI  - Evaluation of selected mechanical properties of NiTi rotary glide path files
      manufactured from controlled memory wires.
AB  - This study aimed to investigate mechanical properties related to flexibility and
      fracture resistance of controlled memory wiremanufactured nickel-titanium rotary
      glide path files [HyFlex EDM Glide Path File (EDM) and HyFlex GPF (GPF)]. Scout
      RaCe (RaCe) served as control. Bending loads, torsional/cyclic fatigue
      resistance, and screw-in forces were measured. EDM showed a significantly larger
      torque at fracture, a longer time to cyclic fracture in reciprocation and a
      larger screw-in force compared with GPF and RaCe. GPF showed significantly lower
      bending loads and higher angular deflection values than EDM and RaCe, and a
      significantly longer time to cyclic fracture than RaCe. The time to cyclic
      fracture was significantly longer in reciprocation compared with continuous
      rotation in EDM and GPF. It can be concluded that EDM and/or GPF showed higher
      flexibility and cyclic/torsional fatigue resistance compared with RaCe; and that
      reciprocation conferred better cyclic fatigue resistance to EDM and GPF.

PMID- 29593167
TI  - Correlation between clinical severity and type and degree of pectus excavatum in
      twelve brachycephalic dogs.
AB  - The aim of the study was to correlate the clinical severity of pectus excavatum
      with its type and degree based on objective radiographic evaluation. Twelve
      brachycephalic dogs were included. Grading of the clinical severity was done
      based on a 6-point grading score. Thoracic radiographs were used to calculate the
      frontosagittal and vertebral indices at the tenth thoracic vertebra and the
      vertebra overlying the excavatum. Correlation between the clinical severity score
      and frontosagittal and vertebral indices was evaluated using Pearson's
      correlation coefficient. Typical pectus excavatum was recorded in the caudal
      sternum in seven dogs, with a mean clinical severity score of 1.7 +/- 1.4,
      whereas in five dogs, atypical mid-sternal deviation was recorded with a mean
      clinical severity score of 3.8 +/- 0.7. A strong correlation (r=0.7) was recorded
      between the clinical severity score and vertebral index in the atypical form,
      whereas a weak correlation (r=0.02) was recorded in the typical form (P<0.05).
      The clinical severity and degree of pectus excavatum was poorly correlated
      (r=0.3) in the typical form of pectus excavatum, whereas it was strongly
      correlated (r=0.9) in the atypical form. Pectus excavatum in dogs is associated
      with compressive cardiopulmonary dysfunction, which depends mainly on the
      site/type of deviation rather than the degree of deviation.

PMID- 29593168
TI  - A case report on disseminated Rhodococcus equi infection in a Japanese black
      heifer.
AB  - Rhodococcus equi was isolated from the granulomatous lesions of the lung, kidney,
      liver, and hepatic, mesenteric, and abomasum lymph nodes of a Japanese black
      heifer. R. equi isolates were analyzed by polymerase chain reaction for virulence
      associated protein genes. The vapN gene was detected in all the isolates
      examined. This is the first report in which vapN-positive R. equi was isolated
      from cattle in Japan.

PMID- 29593169
TI  - Rural-Urban Disparity in Emergency Care for Acute Myocardial Infarction in Japan.
AB  - BACKGROUND: There are few reports examining regional differences between rural
      prefectures and metropolitan areas in the management of acute myocardial
      infarction (AMI) in Japan.Methods and Results:In the Rural AMI registry, a
      prospective, multi-prefectural registry of AMI in 4 rural prefectures (Ishikawa,
      Aomori, Ehime and Mie), a total of 1,695 consecutive AMI patients were registered
      in 2013. Among them, 1,313 patients who underwent primary percutaneous coronary
      intervention (PPCI) within 24 h of onset were enrolled in this study (Rural
      group), and compared with the cohort data from the Tokyo CCU Network registry for
      AMI in the same period (Metropolitan group, 2,075 patients). The prevalence of
      direct ambulance transport to PCI-capable facilities in the Rural group was
      significantly lower than that in the Metropolitan group (43.8% vs. 60.3%,
      P<0.01), which resulted in a longer onset-to-balloon time (OTB: 225 vs. 210 min,
      P=0.02) and lower prevalence of PPCI in a timely fashion (OTB <=2 h: 11.5% vs.
      20.7%, P<0.01) in the Rural group. Multivariate analysis revealed that direct
      ambulance transport was the strongest predictor for PPCI in a timely fashion
      (odds ratio=4.13, P<0.001). CONCLUSIONS: AMI patients in rural areas were less
      likely to be transported directly to PCI-capable facilities, resulting in time
      delay to PPCI compared with those in metropolitan areas.

PMID- 29593170
TI  - Plant-Associated Microbes: From Rhizobia To Plant Microbiomes.

PMID- 29593171
TI  - Can intraoperative kinematic analysis predict postoperative kinematics following
      total knee arthroplasty? A preliminary.
AB  - The preliminary study analyzed the relationship between intraoperative navigation
      based kinematics and postoperative 2-dimensional/3-dimensional (2D/3D) image
      registration-based kinematics in total knee arthroplasty (TKA). Six knees in 5
      patients were analyzed. All TKA procedures were performed using an image-free
      knee navigation system. Tibial internal rotation was assessed by intraoperative
      knee kinematics. At 1 year after surgery, tibial internal rotation was evaluated
      using a 2D/3D image registration technique under loaded and unloaded conditions.
      The correlation between intraoperative and postoperative data for the tibial
      internal rotation angle at 10 increments of knee flexion was then assessed.
      Difference in the knee flexion angle between the intraoperative and postoperative
      evaluations was adjusted to account for the sagittal cutting angle of the distal
      femur and proximal tibia. A correlation was found between the intraoperative and
      postoperative data for loaded knee flexion with this adjustment (Pearson's r =
      0.725, p = 0.012). However, intraoperative kinematics was not significantly
      correlated with postoperative kinematics in the absence of loading. Larger
      adequately powered prospective studies are now needed to confirm our preliminary
      finding that postoperative loaded kinematics can be predicted by intraoperative
      evaluation. J. Med. Invest. 65:21-26, February, 2018.

PMID- 29593172
TI  - Interleukin-6 Level among Shift and Night Workers in Japan: Cross-Sectional
      Analysis of the J-HOPE Study.
AB  - AIM: Shift workers have a high risk of cardiovascular disease (CVD). Systemic
      inflammation measured has been associated with the risk of CVD onset, in addition
      to classical risk factors. However, the association between work schedule and
      inflammatory cytokine levels remains unclear. The purpose of this study was to
      examine the association between work schedule and interleukin-6 (IL-6)/high
      sensitivity C-reactive protein (hs-CRP) levels among Japanese workers. METHODS:
      The present cross-sectional study was a part of the Japanese Study of Health,
      Occupation and Psychosocial Factors Related Equity (J-HOPE). A total of 5259
      persons who measured inflammatory cytokine were analyzed in this study. One-way
      analysis of variance was used to test log-transformed IL-6/hs-CRP differences by
      work schedule. Multiple regression analysis was used to examine the difference
      adjusted for other possible CVD risk factors. RESULTS: There were 3660
      participants who had a regular work schedule; the remaining schedules were shift
      work without night work for 181 participants, shift work with night work for 1276
      participants, and only night work for 142 participants. The unadjusted model
      showed that only night workers were significantly related to high levels of IL-6
      compared with regular workers. Even in the multiple regression analysis, the
      higher level of IL-6 among only night workers remained significant (beta=0.058,
      P=0.01). On the contrary, hs-CRP was not. CONCLUSION: The present study revealed
      that only night shift work is significantly associated with high levels of IL-6
      in Japanese workers. These observations help us understand the mechanism for the
      association between work schedule and CVD onset.

PMID- 29593173
TI  - [Evaluation of Dissolution Profiles of Famotidine from OTC Drugs].
AB  - In recent years, self-medication has started to receive more attention in Japan
      owing to increasing medical costs and health awareness among people. One of the
      main roles of pharmacists in self-medication is to provide appropriate
      information regarding OTC drugs. However, pharmacists promoting the proper use of
      OTC drugs have little information on their formulation properties. In this study,
      we performed dissolution tests on both OTC drugs and ethical drug (ED) containing
      famotidine, and evaluated the differences in their dissolution profiles. Marked
      differences in dissolution profiles of OTC drugs were observed in test solutions
      at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively,
      we calculated the lag time and dissolution rate constant from the dissolution
      profiles. Significant differences in lag times and dissolution rate constants
      between some OTC drugs and ED were observed. We also used similarity factor (f2),
      to quantify the similarity between dissolution profiles of OTC drugs and ED. f2
      values less than 42 were observed in some OTC drugs, suggesting that these
      differences might influence absorption in vivo resulting in differences in their
      onset time and efficacy. The findings of this study will provide useful
      information for the promotion of proper use of OTC drugs.

PMID- 29593174
TI  - Cytotoxic Lathyrane-Type Diterpenes from Seeds of Euphorbia lathyris.
AB  - We isolated two new lathyrane-type diterpenes L27 (1) and L28 (2) along with
      seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds
      were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as
      well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with 1H
      NMR, 13C-NMR, distortionless enhancement by polarization (DEPT), correlation
      spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC),
      heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect
      spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by
      comprehensive interpretation of their nuclear Overhauser effect (NOE)
      relationship and showed they were first natural lathyrane-type diterpenes
      possessing alpha-configuration substitutes at C-3. Cytotoxicity assay of isolated
      compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231,
      786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L28 (2)
      showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC50
      value of 9.43 and 13.22 uM, respectively, which preliminarily suggested that the
      configuration of lathyrane-type diterpene at C-3 has a significant effect on its
      bioactivity.

PMID- 29593175
TI  - Neopterin and Cardiovascular Events Following Coronary Stent Implantation in
      Patients with Stable Angina Pectoris.
AB  - AIM: Neopterin is an activation marker for monocytes/macrophages. We
      prospectively investigated the predictive value of plasma neopterin levels on 2
      year and long-term cardiovascular events in patients with stable angina pectoris
      (SAP) undergoing coronary stent implantation. METHODS: We studied 123 consecutive
      patients with SAP who underwent primary coronary stenting (44 patients with bare
      metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma
      neopterin levels were measured on admission using HPLC. Moreover, one frozen
      coronary artery specimen after DES and three frozen coronary specimens after BMS
      were obtained by autopsy or endarterectomy, followed by immunohistochemical
      staining for neopterin. RESULTS: Plasma neopterin levels were significantly
      higher in patients with cardiovascular events than in those without them
      (P<0.001). In subgroup analyses, higher levels of plasma neopterin in patients
      with cardiovascular events (P<0.001) and a positive correlation between neopterin
      levels and late lumen loss after stenting (P =0.008) were observed in the BMS
      group but not in the DES group (P=0.53 and P=0.17, respectively). In long-term
      cardiovascular events, multivariate Cox regression analysis identified the
      significance of the high-neopterin group as independent determinants of
      cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283-3.857; P =0.004).
      Immunohistochemical staining showed abundant neopterin-positive macrophages in
      the neointima after BMS implantation but no neopterin-positive macrophages in the
      neointima after DES implantation. CONCLUSION: These findings suggest that
      neopterin is associated with cardiovascular events after coronary stent
      implantation in patients with SAP. However, there might be a strong association
      between neopterin and cardiovascular events after BMS but not after DES in these
      patients.

PMID- 29593176
TI  - [Structure of Relationships Formed by Occupational Health Nurses for Co-operating
      with Managers to Support Workers with Mental Health Concerns].
AB  - OBJECTIVE: Occupational health staff and managers play important roles in
      supporting workers with mental health concerns and mutual co-operation among them
      is a necessary element. However, when co-operating with other professionals,
      several problems arise that often make such co-operation a challenge. Effective
      mutual actions are needed to promote such co-operation, and relationships must be
      formed for this purpose. Therefore, in this study, we aimed to clarify how
      occupational health nurses form relationships for facilitating co-operation with
      managers to provide support to workers with mental health concerns. METHODS: Data
      were collected using semi-structured interviews with 11 occupational health
      nurses who provide individualized mental health support and who have at least 5
      years of experience as occupational health nurses. Analysis of the recorded
      interviews was performed using a qualitative statistical method (KJ method).
      RESULTS: Six elements that constitute the formation of relationships were
      identified. When occupational health nurses form relationships for facilitating
      co-operation with a manager to provide support to workers, they "form
      relationships through strategic communication" with them and when co-operation is
      required, they form a relationship by "acting in a manner that suits the
      manager," such as his/her character and the situation. To support this
      relationship, occupational health nurses "provide mental support to the manager"
      by listening to his/her anxiety or real intention about supporting the
      subordinate with mental health concerns and provide relief while understanding
      their burdens during the co-operation. Occupational health nurses even "provide
      support to the manager in their activities," which assessed the situation at the
      workplace as the specialist and advised the manager to understand how to concern
      to the subordinate specifically. In addition, they "indirectly support the
      manager" which included coordinating with the concerned persons so as to not
      excessively burden the manager. Such support promoted the "creation of systems
      for clear roles" of managers in supporting the subordinate with mental health
      concerns. DISCUSSIONS: Relationships that occupational health nurses form with
      their managers were the structure which formed emotional human relationships from
      the front or back necessity of co-operation causes and developing confidence in
      relationships with the foundation of emotional human relationships.

PMID- 29593177
TI  - Molecular Pathogenesis of Familial Wolff-Parkinson-White Syndrome.
AB  - Familial Wolff-Parkinson-White (WPW) syndrome is an autosomal dominant inherited
      disease and consists of a small percentage of WPW syndrome which exhibits
      ventricular pre-excitation by development of accessory atrioventricular pathway.
      A series of mutations in PRKAG2 gene encoding gamma2 subunit of 5'AMP-activated
      protein kinase (AMPK) has been identified as the cause of familial WPW syndrome.
      AMPK is one of the most important metabolic regulators of carbohydrates and
      lipids in many types of tissues including cardiac and skeletal muscles. Patients
      and animals with the mutation in PRKAG2 gene exhibit aberrant atrioventricular
      conduction associated with cardiac glycogen overload. Recent studies have
      revealed "novel" significance of canonical pathways leading to glycogen synthesis
      and provided us profound insights into molecular mechanism of the regulation of
      glycogen metabolism by AMPK. This review focuses on the molecular basis of the
      pathogenesis of cardiac abnormality due to PRKAG2 mutation and will provide
      current overviews of the mechanism of glycogen regulation by AMPK. J. Med.
      Invest. 65:1-8, February, 2018.

PMID- 29593178
TI  - Geranylgeranylacetone prevents stress-induced decline of leptin secretion in
      mice.
AB  - Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of
      cell and tissue against stress. We examined whether GGA modulated energy intake
      and expenditure under stressful conditions. After mice were untreated or treated
      orally with GGA (0.16 g per kg body weight per day) for 10 days, they were
      subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA
      administration did not affect corticosterone response to the stress. Restraint
      stress rapidly decreased plasma leptin levels in control mice. GGA significantly
      increased circulating leptin levels without changing food intake and prevented
      the stress-induced decline of circulating leptin. However GGA-treated mice
      significantly reduced food intake during the repeated stress, compared with
      control mice. GGA prevented the stress-induced decline of leptin mRNA and its
      protein levels in epidydimal adipose tissues. We also found that GGA decreased
      ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated
      mice recovered the ghrelin mRNA expression to the baseline level after the
      repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety
      and depressive mood. Our results suggest that GGA may regulate food intake and
      relief stress-induced mood disturbance through regulating leptin and ghrelin
      secretions. J. Med. Invest. 65:103-109, February, 2018.

PMID- 29593179
TI  - Virological characterization of HIV-1 CA-NTD mutants constructed in a virus
      lineage reflected manner.
AB  - Capsid (CA) protein is a major virion-constituent of all retroviruses including
      human immunodeficiency virus type 1 (HIV-1), and is essential for early and late
      phases in viral replication cycle through interaction with numerous cellular
      factors. In particular, N-terminal domain (NTD) of HIV-1 CA has been frequently
      and well reported to bind to various host cell proteins that considerably affect
      viral replication potential. In this study, in order to better define biological
      bases of the CA-NTD for HIV-1 replication, we performed an extensive mutational
      analysis in an unprecedented manner. By aligning CA-NTD sequences derived from
      representative infectious molecular clones of HIV-1, HIV-2, and simian
      immunodeficiency virus isolated from the rhesus macaque (SIVmac), a number of
      amino acids specific to HIV-1 were selected, and were replaced with those from
      SIVmac at the corresponding sites. Mutant viruses thus generated were then
      examined for multi-cycle infectivity, single-cycle infectivity, and ability to
      produce progeny virions. While some CA-NTD mutations affected viral replication
      ability to varying degrees, those in helix 7 abolished viral growth potential
      without exception. These results highlight functional importance of non-conserved
      amino acids in helix 7, and give new insights into functionality of HIV-1 CA-NTD.
      J. Med. Invest. 65:110-115, February, 2018.

PMID- 29593180
TI  - The ratio of contrast medium volume to estimated glomerular filtration rate as a
      predictor of contrast-induced nephropathy after endovascular aortic repair.
AB  - OBJECTIVE: This study aimed to determine the perioperative predictors of contrast
      medium-induced nephropathy (CIN) after endovascular aortic repair (EVAR).
      MATERIALS AND METHODS: The data of 203 consecutive patients who underwent
      elective EVAR for thoracic and abdominal aortic aneurysm between January 2014 and
      September 2014 were retrospectively analyzed. CIN was defined according to the
      diagnostic criteria of the European Society of Urogenital Radiology. RESULTS:
      Fourteen patients (6.9%) developed CIN after EVAR. Contrast medium volume (CV),
      preoperative serum creatinine, estimated glomerular filtration rate (eGFR), and
      the CV/eGFR ratio were significantly related with CIN development after EVAR. The
      CV/eGFR ratio was significantly higher in patients with CIN than those without
      CIN. Receiver operator characteristic curve analysis showed that the area under
      the curve of the CV/eGFR ratio was 0.782, indicating that it was the most
      important predictor. The appropriate CV/eGFR ratio cutoff was 1.62. Sensitivity
      and specificity were 85.7% and 65.6%, respectively. CONCLUSIONS: The CV/eGFR
      ratio was a useful predictor of contrast medium-induced nephropathy after EVAR.
      It is possible that the score can be used in patients when managing the EVAR
      techniques and contrast medium volume. J. Med. Invest. 65:116-121, February,
      2018.

PMID- 29593181
TI  - Skeletal muscle mass of old Japanese women suffering from walking difficulty in
      nursing home.
AB  - By using 24 hour urinary creatinine levels, skeletal muscle mass (kg), its rate
      (%) of body weight and creatinine height index (%) were determined in old
      Japanese women suffering from walking difficulty in nursing home and compare with
      those of young university students. Those of old subjects showed approximately 30
      50%, 36-44% and 44-46% of young subjects, respectively. It is suggested that
      these values are important and useful biomarkers for the planning and the
      achievement of rehabilitation program for the maintaining and restoring skeletal
      muscle mass and for the careful support by registered care workers to aged
      persons. J. Med. Invest. 65:122-125, February, 2018.

PMID- 29593182
TI  - High defect stage, contralateral defects, and poor flexibility are negative
      predictive factors of bone union in pediatric and adolescent athletes with
      spondylolysis.
AB  - PURPOSE: To identify predisposition to spondylolysis and physical characteristics
      associated with "bone union" following conservative spondylolysis treatment among
      pediatric and adolescent athletes. METHODS: We retrospectively analyzed pediatric
      and adolescent athletes with spondylolysis who underwent conservative treatment
      and rehabilitation for three or more consecutive months following sports activity
      cessation. Patients with terminal spondylolysis or who did not discontinue sports
      activities were excluded. We compared physical fitness factors in the union and
      nonunion groups and examined the association between bone union and spondylolysis
      severity by logistic regression analysis. RESULTS: Of 183 patients with
      spondylolysis who underwent rehabilitation over a four-year period, 127 patients
      with 227 defects were included in the final analysis. Bone union was achieved in
      66.5% (151/227) of the pars interarticularis defects and 70.1% (89/127) of the
      patients. On multivariate analysis, stage of pars interarticularis defect (odds
      ratio [OR], 0.26;p = 0.0027), stage of contralateral pars interarticularis defect
      (OR, 0.51;p = 0.00026), and straight leg-raising test (OR, 1.06;p = 0.028) were
      significantly associated with bone union. CONCLUSIONS: High defect stage, stage
      of the contralateral pars interarticularis defect, and poor flexibility were
      negative prognostic factors of bone healing in athletes with spondylolysis. J.
      Med. Invest. 65:126-130, February, 2018.

PMID- 29593183
TI  - Evaluation of antigen-positive toxin-negative enzyme immunoassay results for the
      diagnosis of toxigenic Clostridium difficile infection.
AB  - Clostridium difficile (C. difficile)-associated diarrhea (CDAD) is a challenging
      nosocomial infectious disease. C. DIFF Quik Chek Complete assay is widely used to
      detect glutamate dehydrogenase (GDH) antigen and toxin A/B of C. difficile
      simultaneously. However, the interpretation of GDH positive/toxin negative
      results is problematic. We performed a retrospective study of patients with GDH
      positive/toxin negative results to determine the probability of detecting
      toxigenic C. difficile and its risk factors. Between April 2012 and March 2017,
      we investigated cultures of fecal specimens followed by toxin detection tests.
      The clinical histories of patients with and without toxigenic C. difficile were
      compared using univariate- and multivariate-analyses. In total, 2675 patients
      were examined using C. Diff Quik Chek Complete assay. Among 356 GDH
      positive/toxin negative patients, cultures were performed in 220 cases and
      toxigenic C. difficile was recovered from 139 (63.2%) specimens. Patients with
      toxigenic C. difficile had significantly lower body mass index than those
      without. Over half the GDH positive/toxin negative patients were infected with
      toxigenic C. difficile. Lower BMI was a CDAD risk factor in this patient
      population. These data can be utilized to initiate isolation and clinical
      interventions before confirmatory test results are available. J. Med. Invest.
      65:131-135, February, 2018.

PMID- 29593185
TI  - Effectiveness of using non-invasive continuous arterial pressure monitoring with
      ClearSight in hemodynamic monitoring during living renal transplantation in a
      recipient:a case report.
AB  - We investigated the effectiveness of the ClearSight system for hemodynamic
      management during kidney transplantation for a recipient. The recipient was to
      receive a kidney transplant from his mother under general anesthesia. We used
      continuous noninvasive finger-cuff-based monitoring of blood pressure, provided
      by the ClearSight system, and stroke volume variation to predict fluid
      responsiveness. We used of a balanced anesthetic technique and stringent
      monitoring standards to ensure a successful outcome for the patient. This case
      demonstrated that ClearSight has the potential to improve patient monitoring in
      hemodynamically stable patients who received kidney transplantation under general
      anesthesia. J. Med. Invest. 65:139-141, February, 2018.

PMID- 29593184
TI  - Combined resection of re-recurrent lateral lymph nodes and external iliac
      vein:Case Report and Literature.
AB  - Herein, we describe the operative procedure for combined resection of re
      recurrent lateral lymph nodes and the external iliac vein. There is no consensus
      on the clinical implications of resection of locally re-recurrent colorectal
      tumors, as the operative procedure is extremely difficult. We present the case of
      a 52-year-old woman who underwent abdominoperineal resection. About one year
      later, we excised a recurrent lymph node in the left lateral obturator area
      through an extraperitoneal approach. About 18 months later, lymph node re
      recurrence in the left external iliac area was observed. Re-recurrent lymph nodes
      directly invade the left external iliac vein. We removed the re-recurrent lymph
      node with combined, radical segmental resection of the left external iliac vein,
      left obturator artery and vein, and left obturator nerve. J. Med. Invest. 65:136
      138, February, 2018.

PMID- 29593186
TI  - Peritoneal cecal cancer metastasis to a mesh-plug prosthesis:A case report.
AB  - We report the case of a 77-year-old man who presented to our hospital with cecal
      cancer, lung metastasis, and liver metastasis in January 2013. After four courses
      of modified infusional intravenous fluorouracil and levofolinate with oxaliplatin
      (mFOLFOX 6) + bevacizumab, there was no new metastatic lesion and lung metastasis
      reduction was observed. Ileocecal resection was performed in May, left lower lung
      lobectomy in August, and extended right posterior segmentectomy + S8 partial
      liver resection was performed in December. The tumor marker declined
      initially;thereafter, it gradually increased. Computed tomography (CT) performed
      in April 2014 revealed right inguinal mass around the mesh-plug prosthesis. A
      positron emission tomography-CT (PET-CT) also revealed a high 2-fluoro-2-deoxy-D
      glucose (FDG) uptake at the same site. Right inguinal tumor resection was
      performed in July. Cancer tissues were confirmed by performing intraoperative
      rapid pathological diagnosis, and R0 resection could be achieved. Previous
      studies have reported malignant tumor metastases to the mesh-plug prosthesis, and
      this was believed to one of the sites that cancer cells can easily engraft. In
      particular, in patients with a history of advanced malignant tumors, if mass
      formation around the artifact insertion site is observed, the possibility of
      peritoneal metastasis should be considered. J. Med. Invest. 65:142-146, February,
      2018.

PMID- 29593187
TI  - A case of interstitial pneumonia associated with anti-PL-7 antibody in a patient
      with rheumatoid arthritis.
AB  - A 65-year-old female had been treated rheumatoid arthritis (RA), interstitial
      pneumonia (IP) and nephrotic syndrome with prednisolone and cyclosporine. She was
      emergently admitted to our hospital due to the worsening exertional dyspnea and
      severe hypoxemia. Chest computed tomography (CT) showed new diffuse ground-glass
      opacities (GGOs) with slight consolidations along with bronchovascular bundle
      were observed in addition to pre-existing reticular shadows in both lungs with
      lower lobe-predominance. An acute exacerbation (AE) of pre-existing IP triggered
      by an infection was suspected, and the treatment with antibiotics and
      corticosteroid pulse therapy improved her general condition and chest
      radiological findings. Because some auto-antibodies associated with
      acute/subacute onset IP have recently become available in clinic, we examined
      those including anti-aminoacyl tRNA synthetase (ARS) antibodies, and found that
      she was positive for anti-PL-7 antibody. We diagnosed her anti-synthetase
      syndrome (ASS) without symptom of myositis, and her IP was considered to be ASS
      related. The careful consideration is necessary to precisely diagnose and treat
      the patients with RA-associated interstitial lung diseases as the several
      etiologies may be overlapped in the same patient. J. Med. Invest. 65:147-150,
      February, 2018.

PMID- 29593188
TI  - Risk Factor of Mortality in Indonesian Children with Cerebral Palsy.
AB  - OBJECTIVE: Individuals with CP have a lower life expectancy than the general
      population. The objective of the study is to investigate the risk factor of
      mortality in Indonesian children with CP. METHODS: An observational analytic
      study was conducted using medical records at pediatric ward Dr. Soetomo Hospital,
      Surabaya, Indonesia, from January 2014 to December 2016. Inclusion criteria was
      all of CP patients in that were hospitalized from 6 months to 14 year of age.
      Mortality information was obtained from annual computer and matched against the
      subjects with CP on the basis of name, date of birth, type of disability, degree
      of disability, nutritional status and the outcomes. Risk factors were counted
      using logistic regression. RESULT: Fifty five children were enrolled. The outcome
      revaled 12 patients (21.8%) were death. Pneumonia was the most common underlying
      disease cause of death (OR=5.185;95% CI 1.249 to 21.520;Psize 8 < 0.007). Other
      risk factors of mortality that significant were acute kidney injury (AKI)
      (OR=3.333;95% CI 1.317 to 8.436;Psize 8 < 0.03). and Gross Motor Functioning
      Classification System (GMFCS) more than level IV (OR=1.480;95% CI 1.184 to
      1.850;Psize 8 < 0.006). CONCLUSION: Pneumonia, AKI and severe GMFCS level were
      risk factors of death in patients with CP. J. Med. Invest. 65:18-20, February,
      2018.

PMID- 29593189
TI  - Results of Hepatic Resection for Liver Metastasis of Gastric Cancer.
AB  - BACKGROUND: Surgical indication for hepatic resection is controversial in gastric
      cancer liver metastasis (GLM). The aim of this study is to clarify the effect of
      hepatic resection for GLM. METHODOLOGY: Ten patients who underwent hepatic
      resection for GLM between 2001 and 2013 were enrolled in this study. Six patients
      underwent synchronous hepatic resection and gastrectomy, and the remaining four
      patients underwent metachronous hepatic resection. Six patients had solitary
      liver metastasis, and 4 patients had multiple liver metastasis. The median follow
      up period was 12.4 months (the range being 0.5 months to 50 months). RESULT: The
      actual 1- year and 3-year overall survival rates for the patients who underwent
      hepatic resection are 88.9% and 17.8%, respectively. The median survival time was
      21.5 months. And the 1-year recurrence free survival time was 20.0%. The median
      recurrence free survival rate was 4.7 months. Regarding post-operative
      recurrence, synchronous hepatic resection tended to be a recurrence factor
      (p=0.08). CONCLUSION: Hepatic resection for GLM has an acceptable outcome.
      Metachronous hepatic resection tends to have a better outcome than synchronous
      hepatic resection for the treatment of GLM. J. Med. Invest. 65:27-31, February,
      2018.

PMID- 29593190
TI  - Administration of Kampo medicine through a tube at an advanced critical care
      center.
AB  - n emergency and critical care medical centers, tube administration is employed
      for patients who have difficulty swallowing oral drugs owing to decreased
      consciousness or mechanical ventilation. However, tube clogging due to drug
      injection is a concern. We compared the crushing method with the simple
      suspension method for the passage of amlodipine, an antihypertensive drug, in
      combination with rikkunshito, which has been used to treat upper gastrointestinal
      disorders such as functional dyspepsia and gastroesophageal reflux in emergency
      and critical care medical centers, to ascertain the effect of Kampo products on
      the passage of other drugs during tube administration. When the crushing method
      was employed, poorly water-soluble solid products were formed, while a uniformly
      dispersed suspension was obtained using the simple suspension method. In
      addition, the passage rate of amlodipine through the tube was 64% and 93% in the
      crushing and simple suspension methods, respectively, thereby indicating that the
      simple suspension method provided more favorable than the crushing method. The
      results of this study suggested that the passage rate of amlodipine for patients
      who received Kampo products concurrently was higher when the simple suspension
      method was used, and an appropriate drug amount might well be able to
      administered to patients using this method. J. Med. Invest. 65:32-36, February,
      2018.

PMID- 29593191
TI  - Treatment strategy for successful hepatic resection of icteric liver.
AB  - BACKGROUND: The treatment strategy for jaundiced patients with hilar
      cholangiocarcinoma (HC) is not well established. In this study, we evaluate the
      feasibility of our perioperative protocol for jaundiced patients with HC.
      METHODS: Twenty patients with HC who underwent hepatic resection at our institute
      were enrolled, and patients were divided into icteric(n=6) and normal(n=14)
      group. As a perioperative protocol, Oral administration of Inchinkoto(ICKT),
      steroid and nafamostat mesilate were introduced. The evaluation of functional
      future remnant liver(FRL) by asiaroscintigraphy, and postoperative outcomes were
      retrospectively compared. RESULTS: Indocyanine green dye retention rate at 15
      minutes was higher, and LHL15 values was lower in icteric group. However, in the
      functional evaluation of FRL, which was the sum of GSA uptake of the future FRL,
      there was no significant difference of LHL15 values of the remnant liver
      functional reserve between the two groups. As results, according to the
      difference of liver function, serum AST level was not different between two
      groups. The number of patients with postoperative morbidity in the two groups was
      comparable. CONCLUSIONS: Even in HC patients with icteric liver, accurate
      assessment of liver functional reserve and effective perioperative treatment may
      attribute to successful hepatectomy and favorable post-operative outcomes. J.
      Med. Invest. 65:37-42, February, 2018.

PMID- 29593192
TI  - The Effect of Limiting Tapioca Milk Tea on Added Sugar Consumption In Taiwanese
      Young Male and Female Subjects.
AB  - Tapioca milk tea, the most popular beverage in Taiwan, is consumed a lot by
      Taiwanese which contributed to their daily sugar intake. Our study purpose is to
      investigate whether limiting intake of tapioca milk tea is useful for the control
      of sugar intake in Taiwanese. The study was conducted in questionnaires selected
      38 subjects, 20-24 y, from 341 university students in Kaohsiung City, Taiwan.
      Subjects were match-paired by sex, age, department, and randomly divided into two
      groups for cross-over design in which each group had 1 week with or without
      tapioca milk tea. Other beverages and foods were allowed freely in both periods.
      Each group member recorded their own daily sugary intake for two weeks and was
      confirmed by researchers the next day. The average sugar intakes with or without
      tapioca milk tea were similar between the two treatments (p 0.05), 58.4 23.2
      g/day and 56.5 22.2 g/day (glucose 25%, fructose 19%, sucrose 53%, lactose 3%).
      With or without tapioca milk tea, 85% of sugar intakes came from beverages. Even
      by limiting tapioca milk tea, the subjects took the same sugar amount from other
      beverages, suggesting that an established sugar intake level is hard to change.
      J. Med. Invest. 65:43-49, February, 2018.

PMID- 29593193
TI  - Hypophosphatemia occurs with insulin administration during refeeding by total
      parenteral nutrition in rats.
AB  - Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes
      that occur following aggressive nutritional supplementation in malnourished
      patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention
      and treatment in clinical practice. However, the mechanism of hypophosphatemia
      during RFS is unclear because of the lack of an animal model. In this study, we
      developed a rat RFS model as a first step to clarifying the molecular mechanism.
      After establishing the parenteral route, rats were fasted for 5 days and
      refeeding was started using total parenteral nutrition. The animals were infused
      with a high calorie solution with or without insulin administration. Results
      showed that plasma phosphate levels did not decrease in rats infused with the
      high calorie solution alone;in contrast, a 20% reduction compared to baseline was
      observed in rats administered insulin. In addition, rats infused with the high
      calorie solution containing added phosphate did not present with
      hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by
      tube feeding and insulin administration, and demonstrated the importance of
      phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55,
      February, 2018.

PMID- 29593194
TI  - Unilateral rotation in baseball fielder causes low back pain contralateral to the
      hitting side.
AB  - Low back pain (LBP) often occurs in baseball players;however, the characteristics
      of the location of their LBP with respect to their throwing and hitting sides
      have not been clarified. In order to clarify the left-right asymmetry of LBP that
      occurs in baseball players, we surveyed 247 university baseball players using an
      LBP questionnaire. The main investigational items were:throwing and hitting side,
      position at the time of LBP experience, and LBP location. Based upon the
      indication of their throwing and hitting side, subjects were classified into
      unilateral rotational (UR) or bilateral rotational (BR) types. Subjects were also
      classified into categories of LBP location as described by ipsilateral or
      contralateral to dominant side of throwing or hitting. Chi-square test or Fisher
      exact test were used to compare LBP location side by rotational type (UR/BR) in
      all subjects and by position (pitcher/fielder). We found that among fielders, LBP
      occurring contralateral to the hitting side in UR was significantly more frequent
      than that in BR. We conclude that LBP occurred in baseball fielders with a left
      right asymmetry, which suggests that high frequency unilateral rotation causes
      the lumbar region contralateral to the dominant hitting side to be subject to a
      high load. J. Med. Invest. 65:56-59, February, 2018.

PMID- 29593195
TI  - Observation of Ciliary Body Changes during Accommodation Using Anterior OCT.
AB  - AIM: To evaluate the anatomical changes in the ciliary body (CB) during naturally
      stimulated accommodation in children using anterior segment optical coherence
      tomography (OCT). METHODS: This study was a prospective, observational,
      noncomparative case series included 18 eyes of 9 children (8 males and 1 female)
      aged from 4 to 10 years. Ciliary body thickness (CBT) was measured temporally by
      Anterior OCT at 1, 2 and 3 mm posterior to the scleral spur. Measurements were
      performed in the accommodated state and the unaccommodated state (with
      cycloplegia). RESULTS: The mean CBT significantly increased by accommodation at 1
      mm posterior to the scleral spur from 751 42 to 818 40 MUm (P 0.001) and
      significantly decreased at 2 and 3 mm from 506 66 to 445 59 MUm and from 290 54
      to 240 50 MUm respectively (P 0.001). CONCLUSION: During accommodation, the
      anterior portion of the ciliary body thickens, while the posterior portion
      decreases in thickness. These findings imply that the circular ciliary muscles
      are mainly involved in accommodation and not the longitudinal muscles. J. Med.
      Invest. 65:60-63, February, 2018.

PMID- 29593196
TI  - The plasma level changes of VEGF and soluble VEGF receptor-1 are associated with
      high-altitude pulmonary edema.
AB  - Hypoxia-induced plasma levels of VEGF and sFlt-1 are responsible for increased
      vascular permeability occurred in both brain and pulmonary edema. Currently, it
      remains unclear the exact roles of VEGF and sFlt-1 in High Altitude Pulmonary
      Edema (HAPE) pathogenesis. In this study, plasma levels of VEGF and sFlt-1 from
      10 HAPE and 10 non-HAPE subjects were measured and compared. The results showed
      that plasma levels of both VEGF and sFlt-1 in HAPE patients were significantly
      increased as compared to the non-HAPE group. Interestingly, increased plasma
      levels of these two protein factors were markedly reduced after treatments. As
      compared to VEGF, sFlt-1 was much more affected by hypoxia and treatments,
      suggesting this factor was a key factor contributed to HAPE pathogenesis.
      Importantly, the ratio of sFlt-1 and VEGF in group of either non-HAPE or HAPE
      after recovery was significantly lower than the ratio in HAPE patients prior to
      treatments. Our findings suggested that sFlt-1 was a key factor that involved in
      HAPE pathogenesis and the sFlt-1/VEGF ratio could be used as a sensitive
      diagnostic marker for HAPE. J. Med. Invest. 65:64-68, February, 2018.

PMID- 29593197
TI  - Noninvasive continuous blood pressure monitoring by the ClearSight system during
      robot-assisted laparoscopic radical prostatectomy.
AB  - Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed
      in the surgical treatment of prostate cancer. However, the steep Trendelenburg
      position (25) and pneumoperitoneum required for this procedure can sometimes
      cause hemodynamic changes. Although blood pressure is traditionally monitored
      invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The
      Netherlands) enables a totally noninvasive and simple continuous blood pressure
      and cardiac output monitoring based on finger arterial pressure pulse contour
      analysis. We therefore investigated whether noninvasive continuous arterial blood
      pressure measurements using the ClearSight system were comparable to those
      obtained invasively in patients undergoing RALRP. Ten patients scheduled for
      RALRP with American Society of Anesthesiologists physical status I-II were
      included in this study. At each of the seven defined time points, noninvasive and
      invasive blood pressure measurements were documented and compared in each patient
      using Bland-Altman analysis. Although the blood pressure measured with the
      ClearSight system correlated with that measured invasively, a large difference
      between the values obtained by the two devices was noted. The ClearSight system
      was unable to detect blood pressure accurately during RALRP, suggesting that
      blood pressure monitoring using this device alone is not feasible in this small
      patient population. J. Med. Invest. 65:69-73, February, 2018.

PMID- 29593198
TI  - Associations between intake of dietary fermented soy food and concentrations of
      inflammatory markers: a cross-sectional study in Japanese workers.
AB  - Epidemiological investigations have shown that consumption of soybeans or soy
      foods reduces the risk of the development of cardiovascular disease, cancer and
      osteoporosis. The aim of this study was to determine the associations between
      different soy foods and inflammatory markers, including high-sensitivity C
      reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers.
      The cross-sectional study included 1,426 Japanese workers (1,053 men and 373
      women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated
      food frequency questionnaire. Associations of total soy foods, fermented soy
      food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels
      were examined by general linear model regression analysis. We found that total
      fermented soy food intake was inversely associated with multivariable-adjusted
      geometric concentration of IL-6 in men (Q1:1.03 pg/mL, Q5:0.94 pg /mL;P for trend
      = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely
      associated with miso intake (beta = -0.068;p = 0.034) and soy sauce intake in men
      (beta = -0.074;p = 0.018). This study suggests that intake of total fermented soy
      food, miso and soy sauce be associated with IL-6 concentrations in Japanese men.
      J. Med. Invest. 65:74-80, February, 2018.

PMID- 29593199
TI  - Falls among Hospitalized Patients in an Acute Care Hospital: Analyses of Incident
      Reports.
AB  - Falls cause injuries such as fractures, skin lacerations, bleeding, and head
      injury, and could result in more severe medical conditions in hospitalized
      patients. We retrospectively investigated the incidence and characteristics of
      falls among hospitalized patients in an acute care hospital from incident reports
      by hospital staff between January and June 2013. There were 154 falls in 135
      patients, 2 of which resulted in fracture. The average age of patients who fell
      was 63.9 (range 0 to 91) years. Many falls occurred at the bedside (68.2%).
      Approximately half of all falls were related to elimination (46.6%). The most
      common time of discovery of falls was 2:00-2:59 AM (14/154;9.1%), followed by
      early in the morning when patients would actively move. Fall rates in our
      hospital were 1.39 falls per 1,000 patient days. The department of respiratory
      medicine and rheumatology had the highest fall rate (3.08 falls per 1,000 patient
      days), followed by the departments of neurosurgery and neurology (2.98 falls per
      1,000 patient days). This study revealed the characteristics of falls in an acute
      care hospital, and suggests that their notification in the hospital might help
      reduce the incidence of falls in hospitalized patients. J. Med. Invest. 65:81-84,
      February, 2018.

PMID- 29593200
TI  - Role of Epiligament in Ligamentum Flavum Hypertrophy in Patients  with Lumbar
      Spinal Canal Stenosis:a Pilot Study.
AB  - Ligamentum flavum (LF) hypertrophy is one of the main factors of lumbar spinal
      canal stenosis (LSCS). The primary object of this study is to clarify the
      existence of epiligament in the LF and its role in hypertrophy, and to develop an
      LF hypertrophy animal model. A cadaveric spine from a 30-year-old man was used to
      investigate the existence of epiligament in LF. Five LF samples from LSCS
      patients were obtained to evaluate hypertrophied LF. To create a rat model, we
      destabilized the lumbar spine. Each LF was sagittally cut for histological
      evaluation. The epiligament was clearly evident in normal LF specimens, which
      stained pink on Elastica van Gieson and green on Masson Trichrome. One layer was
      observed on the dural side and another on the dorsal side of the LF. LSCS
      patients had an enlarged dorsal epiligament, at around 30 times that of the
      regular thin epiligament on the dural side. The destabilized rat model showed an
      enlarged dorsal epiligament, with a mean thickness 8-fold that of the control. LF
      hypertrophy may be due to enlargement of the dorsal epiligament. Mechanical
      loading of the LF is an important factor for inducing hypertrophy in the rat
      model. J. Med. Invest. 65:85-89, February, 2018.

PMID- 29593201
TI  - Adipose tissue:Critical contributor to the development of prostate cancer.
AB  - The prostate is surrounded by periprostatic adipose tissue. Although adipose
      tissue was thought to play limited physiological roles, it has recently been
      recognized as an active endocrine organ, secreting growth factors and adipokines.
      Epidemiologically, obesity is associated with prostate cancer progression. A
      major mechanism to explain the link between obesity and cancer includes the
      insulin and insulin-like growth factor (IGF)-1 axis, sex steroids, and
      adipokines. When prostate cancer cells invade periprostatic adipose tissue,
      adipose tissue contributes to create the tumor microenvironment, mainly via
      adipokine secretion. Furthermore, direct crosstalk between adipocytes and cancer
      cells can exist. We showed that fatty acid-binding protein 4 (FABP4) released
      from adipocytes was taken up into prostate cancer cells and may act as a carrier
      of an energy source for the invasion. Bone is an adipocyte-rich organ and is the
      common metastatic site of prostate cancer. In the microenvironment of bone
      metastases, tumor cells, osteoblasts, osteoclasts, adipocytes, and other stromal
      cells are interacting with one another and organizing a complex system. Thus,
      growing evidence implicates adipose tissue as a critical contributor to the
      development of prostate cancer. A deeper understanding of the mechanisms leads to
      more effective therapeutic strategies for prostate cancer. J. Med. Invest. 65:9
      17, February, 2018.

PMID- 29593202
TI  - A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine
      S-1 in patients with stage II-IIIA non-small cell lung cancer.
AB  - BACKGROUND: Adjuvant chemotherapy with uracil tegafur (UFT) improved survival
      among patients with completely resected stage I lung adenocarcinoma. S-1, an oral
      dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent
      DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant
      chemotherapy with S-1 would be effective for advanced non-small cell lung cancer
      (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant
      chemotherapy in patients with curatively resected pathological stage bold I back
      10 bold I and bold I back 10 bold I back 20 bold I A NSCLC. METHODS: Adjuvant
      chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of
      S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected
      NSCLC were enrolled in this study from November 2007 through December 2010. The
      primary endpoint was the rate of completion of the scheduled adjuvant
      chemotherapy. The secondary endpoints were safety, overall survival, and relapse
      free survival. RESULTS: Five patients were censored because of disease
      recurrence. The planned 9 courses of S-1 were administered to completion in 8
      patients. Twelve patients completed more than 70% of the planned courses. Grade 3
      adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis
      (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who
      completed more than 70% of the 9 courses demonstrated better overall survival
      than those who completed less than 70%. CONCLUSION: Postoperative administration
      of S-1 may be possible with few severe adverse events as adjuvant chemotherapy
      for patients with curatively resected pathological stage bold I back 10 bold I 
      bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February,
      2018.

PMID- 29593203
TI  - The perifascial areolar tissue and negative pressure wound therapy for one-stage
      skin grafting on exposed bone and tendon.
AB  - BACKGROUND: Factors such as exposed bones or tendons can inhibit wound healing
      and make it a lengthy process unless aggressive debridement or vascularized flap
      surgery are performed. We have developed a new procedure involving simultaneous
      application of a skin graft and perifascial areolar tissue (PAT) and negative
      pressure wound therapy. METHODS: Of 8 patients with wounds, bones, tendons, and
      thick fascia were exposed in 4, 2, and 2 cases, respectively. These wounds were
      adequately covered with PAT, and split-thickness skin grafts were applied
      simultaneously on the PAT with a VACsize 4.9 bigcirc size 3.5 back 115 up 4 roman
      R device. RESULTS: In 6 of 8 cases, the skin graft and PAT were successful, and
      epithelialization was achieved within 4 weeks. PAT adapted but skin graft was
      unsuccessful in one case, and both the skin graft and PAT failed to adapt of a
      pressure ulcer. Using the PAT to overlap more than 400% of the exposed areas
      resulted in better adaptation. CONCLUSIONS: This procedure contributed to
      reducing the burden on the patients because we were able to use a skin graft on
      the exposed areas, without the need for removal of bone or tendons. This
      potentially means patients avoid loss of function in the affected areas and
      achieve better outcomes. J. Med. Invest. 65:96-102, February, 2018.

PMID- 29593204
TI  - Modafinil Dependence: A Case with Attention-Deficit/Hyperactivity Disorder.
AB  - Modafinil is generally known as a drug with low addiction potential. There are
      few case reports in the literature demonstrating that Modafinil, stated being
      capable of diminishing symptoms of attention deficit/hyperactivity disorder
      (ADHD), causes addiction. In the present article a Modafinil addicted ADHD case,
      consuming usurious doses (5,000 mg/per day) of Modafinil is presented. The case
      presented to our psychiatry outpatient clinic due to: requirement of in taking
      high dose Modafinil in order to achieve the initial effects, difficulty in
      obtaining the drug, irritability, anxiousness, sleep irregularities, fatigue and
      unpleasant vivid dreams when he did not use the drug. It was realized that the
      patient, himself increased doses of Modafinil incrementally, in order to keep its
      effects on attention symptoms at the same level. It has to be kept in mind that
      ADHD patients can develop Modafinil addiction. It is necessary to carry out
      systemic studies on this subject.

PMID- 29593205
TI  - Hypomania in Bobble-Head Doll Syndrome: A Case Report of Surgically Treated
      Stereotypy and Hypomania.
AB  - A 22-year-old man was admitted with gradually aggravating stereotypic head
      movement with hypomania. Brain magnetic resonance imaging showed a large
      suprasellar arachnoid cyst extending into the third ventricle, with obstructive
      hydrocephalus, characteristic of bobble-head doll syndrome. Endoscopic
      fenestration of the suprasellar arachnoid cyst was performed. Stereotypic head
      movement stopped immediately after surgery and hypomanic symptoms gradually
      improved within a month. During 4 years of follow-up observation without
      medication, neuropsychiatric symptoms did not relapse. We report our experience
      of surgically treating stereotypy and hypomania in a case of bobble-head doll
      syndrome and discuss the possible neuropsychiatric mechanisms of this rare
      disease.

PMID- 29593206
TI  - Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome
      Patients Quarantined in Hospital: A Retrospective Chart Analysis.
AB  - OBJECTIVE: Little is known about the psychiatric complications or risk factors
      for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS)
      patients quarantined in hospital. METHODS: A retrospective chart review was
      performed of all the patients admitted to the acute MERS inpatient unit at the
      NMC during the 2015 outbreak. RESULTS: 30 (75%) were confirmed to be MERS-CoV
      positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%)
      exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis
      and medication during their hospital stay. Suspected MERS patients did not
      exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or
      confirmed MERS patients (age 41.15+/-18.64, male 37.0%) completed psychological
      assessments. A multiple linear regression analysis revealed that the Korean
      National Health and Nutrition Examination Survey-Short form and the Impact of
      Event Scale-Revised scores were significantly positively correlated with Patient
      Health Questionnaire-9 scores. CONCLUSION: Our findings indicate that the acute
      treatment of MERS-CoV infections in quarantine had a significant impact on the
      patients' mental health. Furthermore, assessment of the risk factors for
      depression may identify vulnerable patients who require psychiatric care and
      attention during hospital quarantine.

PMID- 29593207
TI  - Chasing the Chameleon: Psychogenic Paraparesis Responding to Non-Invasive Brain
      Stimulation.
AB  - Neurologic symptoms that develop unconsciously and are incompatible with known
      pathophysiologic mechanisms or anatomic pathways belong to Conversion Disorder
      (CD). CD diagnosis is based on the clinical history and the exclusion of physical
      disorders causing significant distress or social and occupational impairment. In
      a subgroup of CD, called functional weakness (FW), symptoms affecting limbs may
      be persistent, thus causing a permanent or transient loss of limb function.
      Physiotherapy, pharmacotherapy, hypnotherapy and repetitive transcranial magnetic
      stimulation (rTMS) have been proposed as treatment strategies for FW-CD. Herein,
      we report a 30 year-old male, presenting with lower limb functional paraparesis,
      having obtained positive, objectively, and stable effects from a prolonged r-TMS
      protocol associated to a multidisciplinary approach, including psychological and
      sexuological counseling, and monitored by gait analysis. We postulate that our
      rTMS protocol, combined with a multidisciplinary approach may be the proper
      treatment strategy to improve FW-CD.

PMID- 29593208
TI  - Clinical Characteristics and Correlation Analysis of Subjects with Chronic
      Hepatitis B Virus (HBV) Infection and Sustained Low Levels of Hepatitis B Surface
      Antigen (HBsAg).
AB  - BACKGROUND The aim of this study was to investigate the clinical characteristics
      of individuals with chronic hepatitis B virus (HBV) infection with persistent low
      levels of hepatitis B surface antigen (HBsAg) and to undertake a correlation
      analysis of the clinical characteristics. MATERIAL AND METHODS The study included
      1,204 subjects with chronic HBV infection. Serum HBsAg, HBV envelope antigen
      (HBeAg), and HBV core antigen (HBcAg) levels were measured using the
      chemiluminescent microparticle immunoassay (CMIA) and the neutralization test.
      HBV DNA was measured using real-time fluorescence quantitative polymerase chain
      reaction (RT-FQ-PCR). RESULTS There were 1,023 subjects in the high-level HBsAg
      group (HBsAg level >=10 IU/mL) and 181 subjects in the low-level HBsAg group
      (HBsAg level <10 IU/mL). In the low-level HBsAg group, the main serological
      pattern (93.37%) was HBsAg and HBeAg and HBcAg-positive (HBV-M2), and the
      asymptomatic carrier (ASC) status was 98.34%. The low-level HBsAg group had a
      lower HBV DNA-positive rate compared with the high-level HBsAg group (40.33% vs.
      75.07%), with a normal distribution across all age groups (P>0.05). The low-level
      HBsAg group included an older age group. A low-level of HBsAg was positively
      correlated with a low level of replication of HBV DNA (r=0.452). CONCLUSIONS The
      findings of this study showed that individuals with chronic HBV infection and
      sustained low-levels of HBsAg were an older population and had a lower level of
      replicating HBV DNA when compared with individuals with high levels of HBsAg, and
      the majority (93.7%) were also HBsAg and HBeAg and HBcAg-positive.

PMID- 29593209
TI  - Placental Pathology in Placental Mesenchymal Dysplasia with 13q12.11 Deletion and
      a 25-Week Gestation Female Infant.

PMID- 29593210
TI  - O2 evolution and recovery of the water-oxidizing enzyme.
AB  - In photosystem II, light-induced water oxidation occurs at the Mn4CaO5 cluster.
      Here we demonstrate proton releases, dioxygen formation, and substrate water
      incorporation in response to Mn4CaO5 oxidation in the protein environment, using
      a quantum mechanical/molecular mechanical approach and molecular dynamics
      simulations. In S2, H2O at the W1 site forms a low-barrier H-bond with D1-Asp61.
      In the S2-to-S3 transition, oxidation of OW1H- to OW1*-, concerted proton
      transfer from OW1H- to D1-Asp61, and binding of a water molecule Wn-W1 at OW1*-
      are observed. In S4, W n-W1 facilitates oxo-oxyl radical coupling between OW1*-
      and corner MU-oxo O4. Deprotonation via D1-Asp61 leads to formation of OW1=O4. As
      OW1=O4 moves away from Mn, H2O at W539 is incorporated into the vacant O4 site of
      the O2-evolved Mn4CaO4 cluster, forming a MU-oxo bridge (Mn3-OW539-Mn4) in an
      exergonic process. Simultaneously, Wn-W1 is incorporated as W1, recovering the
      Mn4CaO5 cluster.

PMID- 29593211
TI  - SNAIL1 action in tumor cells influences macrophage polarization and metastasis in
      breast cancer through altered GM-CSF secretion.
AB  - The EMT inducer SNAIL1 regulates breast cancer metastasis and its expression in
      human primary breast tumor predicts for poor outcomes. During tumor progression
      SNAIL1 has multiple effects in tumor cells that can impact metastasis. An
      inflammatory tumor microenvironment also impacts metastasis and recently SNAIL1
      has been implicated as modulating the secretion of cytokines that can influence
      the tumor immune infiltrate. Using a spontaneous genetic model of breast cancer
      metastasis and syngeneic orthotopic transplant experiments we show that the
      action of SNAIL1 in primary breast tumor cells is required for breast tumor
      growth and metastasis. It does so, in part, by regulating production of GM-CSF,
      IL1alpha, IL-6, and TNFalpha by breast cancer cells. The SNAIL1-dependent tumor
      cell secretome modulates the primary tumor-associated macrophage (TAM)
      polarization. GM-CSF alone modulates TAM polarization and impacts breast cancer
      metastasis in vivo. This study highlights another role for breast tumor SNAIL1 in
      cancer progression to metastasis-modulation of the immune microenvironment of
      primary breast tumors.

PMID- 29593212
TI  - Molecular determinants of Yellow Fever Virus pathogenicity in Syrian Golden
      Hamsters: one mutation away from virulence.
AB  - Yellow fever virus (Flavivirus genus) is an arthropod-borne pathogen, which can
      infect humans, causing a severe viscerotropic disease with a high mortality rate.
      Adapted viral strains allow the reproduction of yellow fever disease in hamsters
      with features similar to the human disease. Here, we used the Infectious
      Subgenomic Amplicons reverse genetics method to produce an equivalent to the
      hamster-virulent strain, Yellow Fever Ap7, by introducing a set of four
      synonymous and six nonsynonymous mutations into a single subgenomic amplicon,
      derived from the sequence of the Asibi strain. The resulting strain, Yellow Fever
      Ap7M, induced a disease similar to that described for Ap7 in terms of symptoms,
      weight evolution, viral loads in the liver and lethality. Using the same
      methodology, we produced mutant strains derived from either Ap7M or Asibi viruses
      and investigated the role of each of Ap7M nonsynonymous mutations in its in vivo
      phenotype. This allowed identifying key components of the virulence mechanism in
      hamsters. In Ap7M virus, the reversion of either E/Q27H or E/D155A mutations led
      to an important reduction of both virulence and in vivo replicative fitness. In
      addition, the introduction of the single D155A Ap7M mutation within the E protein
      of the Asibi virus was sufficient to drastically modify its phenotype in hamsters
      toward both a greater replication efficiency and virulence. Finally, inspection
      of the Asibi strain E protein structure combined to in vivo testing revealed the
      importance of an exposed alpha-helix in domain I, containing residues 154 and
      155, for Ap7M virulence in hamsters.

PMID- 29593213
TI  - Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl
      cyclase.
AB  - G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC)
      comprise one of the most studied transmembrane cell signaling pathways. However,
      it is unknown whether the ligand-dependent interactions between these signaling
      molecules are based on random collisions or the rearrangement of pre-coupled
      elements in a macromolecular complex. Furthermore, it remains controversial
      whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes
      a common functional unit. Using a peptide-based approach, we here report evidence
      for the existence of functional pre-coupled complexes of heteromers of adenosine
      A2A receptor and dopamine D2 receptor homodimers coupled to their cognate Gs and
      Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular
      complex provides the necessary frame for the canonical Gs-Gi interactions at the
      AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation
      mediated by a Gs-coupled GPCR.

PMID- 29593214
TI  - Molecular imaging of glycan chains couples cell-wall polysaccharide architecture
      to bacterial cell morphology.
AB  - Biopolymer composite cell walls maintain cell shape and resist forces in plants,
      fungi and bacteria. Peptidoglycan, a crucial antibiotic target and
      immunomodulator, performs this role in bacteria. The textbook structural model of
      peptidoglycan is a highly ordered, crystalline material. Here we use atomic force
      microscopy (AFM) to image individual glycan chains in peptidoglycan from
      Escherichia coli in unprecedented detail. We quantify and map the extent to which
      chains are oriented in a similar direction (orientational order), showing it is
      much less ordered than previously depicted. Combining AFM with size exclusion
      chromatography, we reveal glycan chains up to 200 nm long. We show that altered
      cell shape is associated with substantial changes in peptidoglycan biophysical
      properties. Glycans from E. coli in its normal rod shape are long and
      circumferentially oriented, but when a spheroid shape is induced (chemically or
      genetically) glycans become short and disordered.

PMID- 29593215
TI  - A licensing step links AID to transcription elongation for mutagenesis in B
      cells.
AB  - Activation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to
      initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B
      cells, thus underpinning antibody responses. AID mutates a few hundred other
      loci, but most AID-occupied genes are spared. The mechanisms underlying
      productive deamination versus non-productive AID targeting are unclear. Here we
      show that three clustered arginine residues define a functional AID domain
      required for SHM, CSR, and off-target activity in B cells without affecting AID
      deaminase activity or Escherichia coli mutagenesis. Both wt AID and mutants with
      single amino acid replacements in this domain broadly associate with Spt5 and
      chromatin and occupy the promoter of AID target genes. However, mutant AID fails
      to occupy the corresponding gene bodies and loses association with transcription
      elongation factors. Thus AID mutagenic activity is determined not by locus
      occupancy but by a licensing mechanism, which couples AID to transcription
      elongation.

PMID- 29593216
TI  - Klf4 glutamylation is required for cell reprogramming and early embryonic
      development in mice.
AB  - Temporal and spatial-specific regulation of pluripotency networks is largely
      dependent on the precise modifications of core transcription factors.
      Misregulation of glutamylation is implicated in severe physiological
      abnormalities. However, how glutamylation regulates cell reprogramming and
      pluripotency networks remains elusive. Here we show that cytosolic
      carboxypeptidases 1 (CCP1) or CCP6 deficiency substantially promotes induced
      pluripotent cell (iPSC) induction and pluripotency of embryonic stem cells
      (ESCs). Klf4 polyglutamylation at Glu381 by tubulin tyrosine ligase-like 4
      (TTLL4) and TTLL1 during cell reprogramming impedes its lysine 48-linked
      ubiquitination and sustains Klf4 stability. Klf4-E381A knockin mice display
      impaired blastocyst development and embryonic lethality. Deletion of TTLL4 or
      TTLL1 abrogates cell reprogramming and early embryogenesis. Thus, Klf4
      polyglutamylation plays a critical role in the regulation of cell reprogramming
      and pluripotency maintenance.

PMID- 29593217
TI  - Structural characterization of a highly-potent V3-glycan broadly neutralizing
      antibody bound to natively-glycosylated HIV-1 envelope.
AB  - Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals
      inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy
      requires understanding how antibodies interact with the native oligomannose and
      complex-type N-glycan shield that hides most protein epitopes on HIV-1 envelope
      (Env). Here we present crystal structures, including a 3.8-A X-ray free electron
      laser dataset, of natively glycosylated Env trimers complexed with BG18, the most
      potent V3/N332gp120 glycan-targeting bNAb reported to date. Our structures show
      conserved contacts mediated by common D gene-encoded residues with the N332gp120
      glycan and the gp120 GDIR peptide motif, but a distinct Env-binding orientation
      relative to PGT121/10-1074 bNAbs. BG18's binding orientation provides additional
      contacts with N392gp120 and N386gp120 glycans near the V3-loop base and engages
      protein components of the V1-loop. The BG18-natively-glycosylated Env structures
      facilitate understanding of bNAb-glycan interactions critical for using
      V3/N332gp120 bNAbs therapeutically and targeting their epitope for immunogen
      design.

PMID- 29593218
TI  - Identification and characterization of a novel rodent bocavirus from different
      rodent species in China.
AB  - Members in the genus Bocaparvovirus are closely related to human health and have
      a wide host range. The diverse hosts raise the possibility of crossing species
      barrier, which is a feature of emerging viruses. Among the mammalian hosts,
      rodents are generally acknowledged to be important reservoirs of emerging
      viruses. Here, rodent samples collected from six provinces and autonomous regions
      of China (Liaoning, Inner Mongolia, Tibet, Xinjiang, Guangxi and Yunnan) were
      used to investigate the prevalence and distribution of bocaparvoviruses. By using
      next-generation sequencing first, a partial non-structural protein 1 (NS1) gene
      belonging to a possible novel bocaparvovirus was discovered. Following this, PCR
      based screening of NS1 gene was conducted in 485 rodent samples, with 106
      positive results found in seven rodent species (Rattus norvegicus, Mus musculus,
      Apodemus agrarius, Cricetulus barabensis, Rattus flavipectus, Rattus rattus and
      Rhombomys opimus). Finally, six nearly full-length genomes and three complete CDS
      were obtained and the newly identified bocaparvovirus was tentatively named
      rodent bocavirus (RoBoV). RoBoV has three ORFs: NS1, NP1, and VP, which are
      characteristics of bocaparvoviruses. Phylogenetic analyses revealed that porcine
      bocavirus isolate PBoV-KU14, a member of Ungulate bocaparvovirus 4, was the most
      related virus to RoBoV, with 92.1-92.9% amino acid identities in NS1 protein.
      Alignments of RoBoV-related sequences showed RoBoV isolates could be classified
      into two clades, demonstrating an inter-host genetic diversity. The results
      indicate a potential interspecies transmission of RoBoV between rodents and swine
      and expand our knowledge on bocaparvoviruses in rodent populations.

PMID- 29593219
TI  - Two-thirds of global cropland area impacted by climate oscillations.
AB  - The El Nino Southern Oscillation (ENSO) peaked strongly during the boreal winter
      2015-2016, leading to food insecurity in many parts of Africa, Asia and Latin
      America. Besides ENSO, the Indian Ocean Dipole (IOD) and the North Atlantic
      Oscillation (NAO) are known to impact crop yields worldwide. Here we assess for
      the first time in a unified framework the relationships between ENSO, IOD and NAO
      and simulated crop productivity at the sub-country scale. Our findings reveal
      that during 1961-2010, crop productivity is significantly influenced by at least
      one large-scale climate oscillation in two-thirds of global cropland area.
      Besides observing new possible links, especially for NAO in Africa and the Middle
      East, our analyses confirm several known relationships between crop productivity
      and these oscillations. Our results improve the understanding of climatological
      crop productivity drivers, which is essential for enhancing food security in many
      of the most vulnerable places on the planet.

PMID- 29593220
TI  - Towards Millimeter-wavelength: Transmission-Mode Fresnel-Zone Plate Lens Antennas
      using Plastic Material Porosity Control in Homogeneous Medium.
AB  - We present two transmission-mode dielectric Fresnel-Zone Plate Lens (FZPL)
      antennas for use within the V-band spectrum. The proposed FZPs are realized via
      pure plastic material using two different additive manufacturing processes. The
      proposed FZP lenses are designed with half (lambda/2) and quarter (lambda/4)
      phase correction rings at 60-GHz with 30lambda0 diameter, where lambda0 is the
      free-space wavelength. The permittivity effect for lens sub-zones is controlled
      by material porosity in cube-shaped structures. The 3D printed zone plate lenses
      are built using additive manufacturing plastic materials with a thickness of
      lambda0 and constant relative permittivities equal to 2.76 and 3.6. Different
      types of antenna with cos n -like radiation patterns as lens illuminators are
      analyzed on the vertical plane of the flat lenses to have a high efficiency over
      the considered operating band. Simulations and experimental measurements show a
      reasonably close match, therefore allowing for a reliable predictability.

PMID- 29593221
TI  - Non-invasive detection of severe neutropenia in chemotherapy patients by optical
      imaging of nailfold microcirculation.
AB  - White-blood-cell (WBC) assessment is employed for innumerable clinical procedures
      as one indicator of immune status. Currently, WBC determinations are obtained by
      clinical laboratory analysis of whole blood samples. Both the extraction of blood
      and its analysis limit the accessibility and frequency of the measurement. In
      this study, we demonstrate the feasibility of a non-invasive device to perform
      point-of-care WBC analysis without the need for blood draws, focusing on a
      chemotherapy setting where patients' neutrophils-the most common type of WBC
      become very low. In particular, we built a portable optical prototype, and used
      it to collect 22 microcirculatory-video datasets from 11 chemotherapy patients.
      Based on these videos, we identified moving optical absorption gaps in the flow
      of red cells, using them as proxies to WBC movement through nailfold capillaries.
      We then showed that counting these gaps allows discriminating cases of severe
      neutropenia (<500 neutrophils per uL), associated with increased risks of life
      threatening infections, from non-neutropenic cases (>1,500 neutrophils per uL).
      This result suggests that the integration of optical imaging, consumer
      electronics, and data analysis can make non-invasive screening for severe
      neutropenia accessible to patients. More generally, this work provides a first
      step towards a long-term objective of non-invasive WBC counting.

PMID- 29593222
TI  - CD4+ and CD8+ T Cells Exert Regulatory Properties During Experimental Acute
      Aristolochic Acid Nephropathy.
AB  - Experimental aristolochic acid nephropathy is characterized by transient acute
      proximal tubule necrosis and inflammatory cell infiltrates followed by
      interstitial fibrosis and tubular atrophy. The respective role of T-cell
      subpopulations has never been studied in the acute phase of the mouse model, and
      was heretofore exclusively investigated by the use of several depletion
      protocols. As compared to mice injected with aristolochic acids alone, more
      severe acute kidney injury was observed after CD4+ or CD8+ T-cells depletion. TNF
      alpha and MCP-1 mRNA renal expressions were also increased. In contrast,
      regulatory T-cells depletion did not modify the severity of the aristolochic
      acids induced acute kidney injury, suggesting an independent mechanism.
      Aristolochic acids nephropathy was also associated with an increased proportion
      of myeloid CD11bhighF4/80mid and a decreased proportion of their counterpart
      CD11blowF4/80high population. After CD4+ T-cell depletion the increase in the
      CD11bhighF4/80mid population was even higher whereas the decrease in the
      CD11blowF4/80high population was more marked after CD8+ T cells depletion. Our
      results suggest that CD4+ and CD8+ T-cells provide protection against AA-induced
      acute tubular necrosis. Interestingly, T-cell depletion was associated with an
      imbalance of the CD11bhighF4/80mid and CD11blowF4/80high populations.

PMID- 29593223
TI  - Latitudinal trends in human primary activities: characterizing the winter day as
      a synchronizer.
AB  - This work analyzes time use surveys from 19 countries (17 European and 2
      American) in the middle latitude (38-61 degree) accounting for 45% of world
      population in this range. Time marks for primary activities are contrasted
      against light/dark conditions. The analysis reveals winter sunrise synchronizes
      labor start time below 54 degree, occurring within winter civil twilight. Winter
      sunset is a source of synchronization for labor end times. Winter terminator
      punctuate meal times in Europe: dinner occurs 3 h after winter sunset time within
      1 h; 40% narrower than variability of dinner local times. The sleep-wake cycle of
      laborers is shown to be related to winter sunrise whereas standard population's
      appears to be irrespective of latitude. The significance of the winter terminator
      depends on two competing factors average labor time (~7 h30 m) and the shortest
      photoperiod. Winter terminator gains significance when both roughly matches. That
      is within a latitude range from 38 degree to 54 degree. The significance of
      winter terminator as a source of synchronization is also related to contemporary
      year round time schedules: the shortest photoperiod represents the worst case
      scenario the society faces.

PMID- 29593224
TI  - Evaluation of TRMM 3B43 data over the Yangtze River Delta of China.
AB  - Tropical Rainfall Measuring Mission (TRMM) 3B43 rainfall products during the
      period of 1998~2016 are evaluated via monthly and yearly precipitation data from
      56 observational stations over the Yangtze River Delta (YRD). The results are as
      follows: (1) annual rainfall increases gradually from northwest to southwest and
      monthly precipitation surges sharply, owing to rainband's abrupt pushing north
      caused by the westward and northward extension of Western Pacific Subtropical
      High, to 200 mm/month in July; (2) only seized by the TRMM, the developing
      process of ChunAn precipitation center synchronizes with monthly precipitation
      series that may recycle throughout the year; (3) 3B43 data are inclined to
      overestimate precipitation but performs the best (relative bias ranging within 
      10~10%) at most parts of the YRD zone; and its correlation coefficient with
      observation is 0.88 in annual scale; for monthly scale, CC peaks in March (0.96)
      and reaches the bottom (0.79) in August; (4) no evident connection between CC and
      elevation is found in the 3B43 annual rainfall products which estimate
      precipitation better upon urban land. This paper is of importance in
      understanding the impacts of complex topography and landcovers on the
      precipitation assessment in a river delta scale.

PMID- 29593225
TI  - Large-scale sequence analysis reveals novel human-adaptive markers in PB2 segment
      of seasonal influenza A viruses.
AB  - To elucidate the adaptive strategies of influenza A viruses (IAVs) to human, we
      proposed a computational approach to identify human-adaptive mutations in
      seasonal IAVs, which have not been analyzed comprehensively. We compared
      representative PB2 sequences of 1425 avian IAVs and 2176 human IAVs and
      identified a total of 42 human-adaptive markers, including 28 and 31 markers in
      PB2 proteins of seasonal viruses H1N1 and H3N2, respectively. Notably, this
      comprehensive list encompasses almost all the markers identified in prior
      computational studies and 21 novel markers including an experimentally verified
      mutation K526R, suggesting the predictive power of our method. The strength of
      our analysis derives from the enormous amount of recently available sequences as
      well as the recognition that human-adaptive mutations are not necessarily
      conserved across subtypes. We also utilized mutual information to profile the
      inter-residue coevolution in PB2 protein. A total of 35 and 46 coevolving site
      pairs are identified in H1N1 and H3N2, respectively. Interestingly, 13 out of the
      28 (46.4%) identified markers in H1N1 and 16 out of the 31 (51.6%) in H3N2 are
      embraced in the coevolving pairs. Many of them are paired with well-characterized
      human-adaptive mutations, indicating potential epistatic effect of these
      coevolving residues in human adaptation. Additionally, we reconstructed the PB2
      evolutionary history of seasonal IAVs and demonstrated the distinct adaptive
      pathway of PB2 segment after reassortment from H1 to H3 lineage. Our study may
      provide clues for further experimental validation of human-adaptive mutations and
      shed light on the human adaptation process of seasonal IAVs.

PMID- 29593226
TI  - Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.
AB  - Caffeine is the most frequently used medication in premature infants. It is the
      respiratory stimulant of choice for apnea associated with prematurity and has
      been called the silver bullet in neonatology because of many proven benefits and
      few known risks. Research has revealed that sedative/anesthetic drugs trigger
      apoptotic death of neurons and oligodendrocytes in developing mammalian brains.
      Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in
      developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a
      neurodevelopmental age comparable to premature human infants, were exposed in
      utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and
      examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3
      fold for neurons and 3.4 fold for oligodendrocytes compared to control brains.
      Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to
      control levels but did not augment oligoapoptosis. Neuronal death was
      particularly pronounced in the basal ganglia and cerebellum. Higher blood levels
      of caffeine within the range considered therapeutic and safe for human infants
      correlated with increased neuroapoptosis. Caffeine markedly augments
      neurotoxicity of isoflurane in the fetal macaque brain and challenges the
      assumption that caffeine is safe for premature infants.

PMID- 29593227
TI  - The Cish SH2 domain is essential for PLC-gamma1 regulation in TCR stimulated CD8+
      T cells.
AB  - Cish, participates within a multi-molecular E3 ubiquitin ligase complex, which
      ubiquitinates target proteins. It has an inhibitory effect on T cell activation
      mediated by PLC-gamma1 regulation, and it functions as a potent checkpoint in
      CD8+ T cell tumor immunotherapy. To study the structural and functional
      relationships between Cish and PLC-gamma1 during CD8+ T cell activation, we
      tested mutants of the Cish-SH2 (R107K) and D/BC (L222Q, C226Q) domains. We
      confirmed that Cish-SH2-specific binding was essential for PLC-gamma1
      ubiquitination and degradation. This domain was essential for the Cish-mediated
      inhibition of Ca2+ release upon TCR stimulation. No effect on inhibition of
      cytokine release was observed with SH2 or D/BC mutants, although the absence of
      Cish led to an increased release of IFN-gamma and TNF-alpha. Using imaging we
      showed that Cish was expressed mostly in the cytoplasm and we did not see any
      Cish clustering at the plasma membrane upon stimulation. We conclude that the
      Cish-SH2 domain is essential for PLC-gamma1 regulation in TCR-stimulated CD8+ T
      cells.

PMID- 29593228
TI  - Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and
      dysfunctional angiogenesis.
AB  - Chronic kidney disease (CKD) is associated with excessive mortality from
      cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of
      CVD, is consistently observed in CKD patients and might be linked to structural
      defects of the microcirculation including microvascular rarefaction. However,
      patterns of microvascular rarefaction in CKD and their relation to functional
      deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo
      microscopy study of the cremaster muscle microcirculation in BALB/c mice with
      moderate to severe uremia, we show in two experimental models (adenine feeding or
      subtotal nephrectomy), that serum urea levels associate incrementally with a
      distinct microangiopathy. Structural changes were characterized by a
      heterogeneous pattern of focal microvascular rarefaction with loss of coherent
      microvascular networks resulting in large avascular areas. Corresponding
      microvascular dysfunction was evident by significantly diminished blood flow
      velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the
      cremaster muscle paralleled rarefaction in the myocardium, which was accompanied
      by a decrease in transcription levels not only of the transcriptional regulator
      HIF-1alpha, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP
      9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia
      in mice associates with systemic microvascular disease with rarefaction, tissue
      hypoxia and dysfunctional angiogenesis.

PMID- 29593229
TI  - Effects of smoking habit change on all-cause mortality and cardiovascular
      diseases among patients with newly diagnosed diabetes in Korea.
AB  - This study aimed to investigate the effects of smoking habit change on the risks
      of all-cause mortality and cardiovascular diseases (CVDs) among patients with
      newly diagnosed diabetes using the Korean National Sample Cohort data. Survival
      regression analyses for the risks of all-cause mortality and CVDs were performed.
      Quitters without body mass index (BMI) change (adjusted hazard ratio [aHR], 0.68;
      95% confidence interval [CI], 0.46-1.00) and quitters with BMI loss (aHR, 1.76;
      95% CI, 1.13-2.73) showed significantly reduced and substantially the increased
      risk of all-cause mortality, respectively, compared with sustained smokers.
      Smoking reduction after diabetes diagnosis may have potential positive effects.
      However, definite benefits on the health outcomes were not identified in this
      study. Participants who started smoking after diabetes diagnosis had higher risks
      of all-cause mortality and CVDs than those who were never smokers or ex-smokers,
      although not statistically significant. In conclusion, smoking cessation after
      diabetes diagnosis could reduce the risks of all-cause mortality and
      cardiovascular events among patients with newly diagnosed diabetes when
      accompanied by proper weight management. Therefore, physicians should advice
      patients with newly diagnosed type 2 diabetes on the importance of smoking
      cessation in combination with long-term weight management to maximize the
      benefits of smoking cessation.

PMID- 29593230
TI  - Renormalized vibrations and normal energy transport in 1d FPU-like discrete
      nonlinear Schrodinger equations.
AB  - For one-dimensional (1d) nonlinear atomic lattices, the models with on-site
      nonlinearities such as the Frenkel-Kontorova (FK) and phi4 lattices have normal
      energy transport while the models with inter-site nonlinearities such as the
      Fermi-Pasta-Ulam-beta (FPU-beta) lattice exhibit anomalous energy transport. The
      1d Discrete Nonlinear Schrodinger (DNLS) equations with on-site nonlinearities
      has been previously studied and normal energy transport has also been found.
      Here, we investigate the energy transport of 1d FPU-like DNLS equations with
      inter-site nonlinearities. Extended from the FPU-beta lattice, the renormalized
      vibration theory is developed for the FPU-like DNLS models and the predicted
      renormalized vibrations are verified by direct numerical simulations same as the
      FPU-beta lattice. However, the energy diffusion processes are explored and normal
      energy transport is observed for the 1d FPU-like DNLS models, which is different
      from their atomic lattice counterpart of FPU-beta lattice. The reason might be
      that, unlike nonlinear atomic lattices where models with on-site nonlinearities
      have one less conserved quantities than the models with inter-site
      nonlinearities, the DNLS models with on-site or inter-site nonlinearities have
      the same number of conserved quantities as the result of gauge transformation.

PMID- 29593231
TI  - Metabolomic approach for a rapid identification of natural products with
      cytotoxic activity against human colorectal cancer cells.
AB  - The discovery of bioactive compounds from natural sources entails an extremely
      lengthy process due to the timescale and complexity of traditional methodologies.
      In our study, we used a rapid NMR based metabolomic approach as tool to identify
      secondary metabolites with anti-proliferative activity against a panel of human
      colorectal cancer cell lines with different mutation profiles. For this purpose,
      fourteen Fabaceae species of Mediterranean vegetation were investigated using a
      double screening method: 1H NMR profiling enabled the identification of the main
      compounds present in the mixtures, whilst parallel biological assays allowed the
      selection of two plant extracts based on their strong anti-proliferative
      properties. Using high-resolution 2D NMR spectroscopy, putative active
      constituents were identified in the mixture and isolated by performing a bio
      guided fractionation of the selected plant extracts. As a result, we found two
      active principles: a cycloartane glycoside and protodioscin derivative.
      Interestingly, these metabolites displayed a preferential anti-proliferative
      effect on colon cancer cell lines with an intrinsic resistance to anti-EGFR
      therapies. Our work provides an NMR-based metabolomic approach as a powerful and
      efficient tool to discover natural products with anticancer activities
      circumventing time-consuming procedures.

PMID- 29593232
TI  - Cross-talk between primary osteocytes and bone marrow macrophages for
      osteoclastogenesis upon collagen treatment.
AB  - Homeostasis of osteoclast formation from bone marrow macrophages (BMM) is
      regulated by paracrine signals of the neighbourhood bone cells particularly
      mesenchymal stem cells (MSC), osteoblasts and osteocytes (OC). Besides paracrine
      cues, collagen and glycosaminoglycan are involved in controlling bone
      homeostasis. Towards this approach, different molecular weight collagens were
      reacted with MSC, OC and BMM to understand the bone homeostasis activity of
      collagen. The up-regulating effect of collagens on osteogenic cell growth was
      confirmed by the presence of mineralized nodules in the osteoblastogenic lineage
      cells and increased osteogenic stimulatory gene expression. The decreased BMM
      derived TRAP+ osteoclasts number and osteoclastogenic regulatory gene expression
      of OC could demonstrate the exploitive osteoclastogenic activity of collagens.
      Osteoclastogenesis from BMM was triggered by paracrine cues of OC in some extend,
      but it was down-regulated by collagen. Overall, the effect of collagen on
      osteoclastogenesis and osteoblastogenesis may depend on the molecular weight of
      collagens, and collagen suppresses osteoclastogenesis, at least in part by
      downregulating the secretion of cytokines in OC.

PMID- 29593233
TI  - Mechanism of translation control of the alternative Drosophila melanogaster
      Voltage Dependent Anion-selective Channel 1 mRNAs.
AB  - The eukaryotic porin, also called the Voltage Dependent Anion-selective Channel
      (VDAC), is the main pore-forming protein of the outer mitochondrial membrane. In
      Drosophila melanogaster, a cluster of genes evolutionarily linked to VDAC is
      present on chromosome 2L. The main VDAC isoform, called VDAC1 (Porin1), is
      expressed from the first gene of the cluster. The porin1 gene produces two splice
      variants, 1A-VDAC and 1B-VDAC, with the same coding sequence but different 5'
      untranslated regions (UTRs). Here, we studied the influence of the two 5' UTRs,
      1A-5' UTR and 1B-5' UTR, on transcription and translation of VDAC1 mRNAs. In
      porin-less yeast cells, transformation with a construct carrying 1A-VDAC results
      in the expression of the corresponding protein and in complementation of a
      defective cell phenotype, whereas the 1B-VDAC sequence actively represses VDAC
      expression. Identical results were obtained using constructs containing the two
      5' UTRs upstream of the GFP reporter. A short region of 15 nucleotides in the 1B
      5' UTR should be able to pair with an exposed helix of 18S ribosomal RNA (rRNA),
      and this interaction could be involved in the translational repression. Our data
      suggest that contacts between the 5' UTR and 18S rRNA sequences could modulate
      the translation of Drosophila 1B-VDAC mRNA. The evolutionary significance of this
      finding is discussed.

PMID- 29593234
TI  - Case-control analysis of LRRK2 protective variants in Essential Tremor.
AB  - Co-existence of Parkinson's disease (PD) and essential tremor (ET) may reflect
      overlapping pathophysiology underlying both conditions. Furthermore, PD patients
      with leucine-rich repeat kinase-2 (LRRK2) mutations may present with ET-like
      features, suggesting the possibility of common genetic underpinnings. Two common
      LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple PD
      cohorts. We hypothesized that R1398H and N551K may show a similar effect in ET.
      In a case-control study involving 3198 subjects (2680 controls and 518 ET cases),
      R1398H was detected in 16.6% of ET cases compared to 18.0% in controls (OR =
      0.91, 95% CI = 0.71-1.17, p = 0.46); while N551K was detected in 16.5% of ET
      cases compared to 18.0% of controls (OR = 0.89, 95% CI = 0.69-1.15, p = 0.37).
      While these results suggest that LRRK2 R1398H or N551K do not appear to modulate
      the risk of ET, it remains possible that a protective trend for both variants may
      be present in ET and a much larger sample size is required to identify this.

PMID- 29593235
TI  - Dual-comb spectroscopy of laser-induced plasmas.
AB  - Dual-comb spectroscopy has become a powerful spectroscopic technique in
      applications that rely on its broad spectral coverage combined with high
      frequency resolution capabilities. Experiments to date have primarily focused on
      detection and analysis of multiple gas species under semi-static conditions, with
      applications ranging from environmental monitoring of greenhouse gases to high
      resolution molecular spectroscopy. Here, we utilize dual-comb spectroscopy to
      demonstrate broadband, high-resolution, and time-resolved measurements in a laser
      induced plasma. As a demonstration, we simultaneously detect trace amounts of Rb
      and K in solid samples with a single laser ablation shot, with transitions
      separated by over 6 THz (13 nm) and spectral resolution sufficient to resolve
      isotopic and ground state hyperfine splittings of the Rb D2 line. This new
      spectroscopic approach offers the broad spectral coverage found in the powerful
      techniques of laser-induced breakdown spectroscopy (LIBS) while providing the
      high-resolution and accuracy of cw laser-based spectroscopies.

PMID- 29593236
TI  - Illusory occlusion affects stereoscopic depth perception.
AB  - When occlusion and binocular disparity cues conflict, what visual features
      determine how they combine? Sensory cues, such as T-junctions, have been
      suggested to be necessary for occlusion to influence stereoscopic depth
      perception. Here we show that illusory occlusion, with no retinal sensory cues,
      interacts with binocular disparity when perceiving depth. We generated illusory
      occlusion using stimuli filled in across the retinal blind spot. Observers viewed
      two bars forming a cross with the intersection positioned within the blind spot.
      One of the bars was presented binocularly with a disparity signal; the other was
      presented monocularly, extending through the blind spot, with no defined
      disparity. When the monocular bar was perceived as filled in through the blind
      spot, it was perceived as occluding the binocular bar, generating illusory
      occlusion. We found that this illusory occlusion influenced perceived
      stereoscopic depth: depth estimates were biased to be closer or farther,
      depending on whether a bar was perceived as in front of or behind the other bar,
      respectively. Therefore, the perceived relative depth position, based on filling
      in cues, set boundaries for interpreting metric stereoscopic depth cues. This
      suggests that filling-in can produce opaque surface representations that can
      trump other depth cues such as disparity.

PMID- 29593237
TI  - Long-range dependence in earthquake-moment release and implications for
      earthquake occurrence probability.
AB  - Since the beginning of the 1980s, when Mandelbrot observed that earthquakes occur
      on 'fractal' self-similar sets, many studies have investigated the dynamical
      mechanisms that lead to self-similarities in the earthquake process. Interpreting
      seismicity as a self-similar process is undoubtedly convenient to bypass the
      physical complexities related to the actual process. Self-similar processes are
      indeed invariant under suitable scaling of space and time. In this study, we show
      that long-range dependence is an inherent feature of the seismic process, and is
      universal. Examination of series of cumulative seismic moment both in Italy and
      worldwide through Hurst's rescaled range analysis shows that seismicity is a
      memory process with a Hurst exponent H ~ 0.87. We observe that H is substantially
      space- and time-invariant, except in cases of catalog incompleteness. This has
      implications for earthquake forecasting. Hence, we have developed a probability
      model for earthquake occurrence that allows for long-range dependence in the
      seismic process. Unlike the Poisson model, dependent events are allowed. This
      model can be easily transferred to other disciplines that deal with self-similar
      processes.

PMID- 29593238
TI  - Three Hcp homologs with divergent extended loop regions exhibit different
      functions in avian pathogenic Escherichia coli.
AB  - Type VI secretion systems (T6SSs) contribute to the pathogenicity of avian
      pathogenic Escherichia coli (APEC), one of the leading causative agents of sepsis
      and meningitis in poultry. The Hcp protein is a core component of the T6SS tail
      tube and acts as an exported receptor and a chaperone of effectors. In this
      study, four distinct Hcp types (Ia, Ib, IIa, and IIb) were designated in Gram
      negative bacteria, three of which were widely distributed in APEC. We detected
      divergence in transcription levels among three hcp clusters in 50% duck serum and
      demonstrated that hcp1 was upregulated by relieving Fur repression. Further
      analyses revealed that the host serum could activate the hcp2B operon by H-NS
      derepression to transcribe the downstream xmtU/xmtV pair for inter-bacterial
      antagonism. Notably, in a structural analysis based on the genetic
      classification, Hcp proteins exhibited significant differences in the extended
      loop regions, suggesting that these regions were related to their functional
      properties. Indeed, the variant region Vs2 (Loop L2, 3) in Hcp1 and Hcp2B was
      essential for the delivery of antibacterial effectors and the inhibition of
      macrophage phagocytosis. Further analyses using a duck model indicated that these
      Hcps play different roles in the pathogenic processes of APEC and
      immunoprotection. These results indicated that the functional differentiation of
      Hcp homologs was driven by differences in transcriptional regulation, extended
      loop regions, and effector delivery.

PMID- 29593239
TI  - Attenuated Notch signaling in schizophrenia and bipolar disorder.
AB  - The Notch signaling pathway plays a crucial role in neurodevelopment and in adult
      brain homeostasis. We aimed to further investigate Notch pathway activity in
      bipolar disorder (BD) and schizophrenia (SCZ) by conducting a pathway analysis.
      We measured plasma levels of Notch ligands (DLL1 and DLK1) using enzyme
      immunoassays in a large sample of patients (SCZ n = 551, BD n = 246) and healthy
      controls (HC n = 639). We also determined Notch pathway related gene expression
      levels by microarray analyses from whole blood in a subsample (SCZ n = 338, BD n
      = 241 and HC n = 263). We found significantly elevated Notch ligand levels in
      plasma in both SCZ and BD compared to HC. Significant gene expression findings
      included increased levels of RFNG and KAT2B (p < 0.001), and decreased levels of
      PSEN1 and CREBBP in both patient groups (p < 0.001). RBPJ was significantly lower
      in SCZ vs HC (p < 0.001), and patients using lithium had higher levels of RBPJ (p
      < 0.001). We provide evidence of altered Notch signaling in both SCZ and BD
      compared to HC, and suggest that Notch signaling pathway may be disturbed in
      these disorders. Lithium may ameliorate aberrant Notch signaling. We propose that
      drugs targeting Notch pathway could be relevant in the treatment of psychotic
      disorders.

PMID- 29593240
TI  - Preparation of Zr(Mo,W)2O8 with a larger negative thermal expansion by
      controlling the thermal decomposition of Zr(Mo,W)2(OH,Cl)2?2H2O.
AB  - Solid solutions of Zr(Mo,W)2O7(OH,Cl)2?2H2O with a preset ratio of components
      were prepared by a hydrothermal method. The chemical composition of the solutions
      was determined by energy dispersive X-ray spectroscopy (EDX). For all the samples
      of ZrMoxW2-xO7(OH,Cl)2?2H2O (x = 0.0, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6,
      1.8, and 2.0), TGA and in situ powder X-ray diffraction (PXRD) studies (300-1100
      K) were conducted. For each case, the boundaries of the transformations were
      determined: Zr(Mo,W)2O7(OH,Cl)2?2H2O -> orthorhombic-ZrMoxW2-xO8 (425-525 K),
      orthorhombic-ZrMoxW2-xO8 -> cubic-ZrMoxW2-xO8 (700-850 K), cubic-ZrMoxW2-xO8 ->
      trigonal-ZrMoxW2-xO8 (800-1050 K for x > 1) and cubic-ZrMoxW2-xO8 -> oxides (1000
      1075 K for x <= 1). The cell parameters of the disordered cubic-ZrMoxW2-xO8
      (space group Pa-3) were measured within 300-900 K, and the thermal expansion
      coefficients were calculated: -3.5?10-6 - -4.5?10-6 K-1. For the ordered
      ZrMo1.8W0.2O8 (space group P213), a negative thermal expansion (NTE) coefficient 
      9.6?10-6 K-1 (300-400 K) was calculated. Orthorhombic-ZrW2O8 is formed upon the
      decomposition of ZrW2O7(OH,Cl)2?2H2O within 500-800 K.

PMID- 29593241
TI  - Identification and DNA annotation of a plasmid isolated from Chromobacterium
      violaceum.
AB  - Chromobacterium violaceum is a beta-proteobacterium found widely worldwide with
      important biotechnological properties and is associated to lethal sepsis in
      immune-depressed individuals. In this work, we report the discover, complete
      sequence and annotation of a plasmid detected in C. violaceum that has been
      unnoticed until now. We used DNA single-molecule analysis to confirm that the
      episome found was a circular molecule and then proceeded with NGS sequencing.
      After DNA annotation, we found that this extra-chromosomal DNA is probably a
      defective bacteriophage of approximately 44 kilobases, with 39 ORFs comprising,
      mostly hypothetical proteins. We also found DNA sequences that ensure proper
      plasmid replication and partitioning as well as a toxin addiction system. This
      report sheds light on the biology of this important species, helping us to
      understand the mechanisms by which C. violaceum endures to several harsh
      conditions. This discovery could also be a first step in the development of a DNA
      manipulation tool in this bacterium.

PMID- 29593242
TI  - The role of CSF1R-dependent macrophages in control of the intestinal stem-cell
      niche.
AB  - Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of
      macrophages.CSF1R signaling has been implicated in the maintenance of the
      intestinal stem cell niche and differentiation of Paneth cells, but evidence of
      expression of CSF1R within the crypt is equivocal. Here we show that CSF1R
      dependent macrophages influence intestinal epithelial differentiation and
      homeostasis. In the intestinal lamina propria CSF1R mRNA expression is restricted
      to macrophages which are intimately associated with the crypt epithelium, and is
      undetectable in Paneth cells. Macrophage ablation following CSF1R blockade
      affects Paneth cell differentiation and leads to a reduction of Lgr5+ intestinal
      stem cells. The disturbances to the crypt caused by macrophage depletion
      adversely affect the subsequent differentiation of intestinal epithelial cell
      lineages. Goblet cell density is enhanced, whereas the development of M cells in
      Peyer's patches is impeded. We suggest that modification of the phenotype or
      abundance of macrophages in the gut wall alters the development of the intestinal
      epithelium and the ability to sample gut antigens.

PMID- 29593243
TI  - Author Correction: The contribution of predators and scavengers to human well
      being.
AB  - In the version of this Review originally published, there were a number of errors
      that the authors wish to correct.

PMID- 29593244
TI  - Author Correction: Intergenerational equity can help to prevent climate change
      and extinction.
AB  - The original Article mistakenly coded the constitutional rights of Australia as
      containing a governmental duty to protect the environment (blue in the figures);
      this has been corrected to containing no explicit mention of environmental
      protection (orange in the figures). The original Article also neglected to code
      the constitutional rights of the Cayman Islands (no data; yellow in the figures);
      this has been corrected to containing a governmental duty to protect the
      environment (blue in the figures).Although no inferences changed as a result of
      these errors, many values changed slightly and have been corrected. The
      proportion of the world's nations having constitutional rights to a healthy
      environment changed from 75% to 74%. The proportions of nations in different
      categories given in the Fig. 1 caption all changed except purple countries
      (3.1%): green countries changed from 47.2% to 46.9%; blue countries changed from
      24.4% to 24.2%; and orange countries changed from 25.3% to 25.8%. The proportion
      of the global atmospheric CO2 emitted by the 144 nations changed from 72.6% to
      74.4%; the proportion of the world's population represented by the 144 nations
      changed from 84.9% to 85%. The values of annual average CO2 emissions for blue
      countries changed from 363,000 Gg to 353,000 Gg and for orange countries from
      195,000 Gg to 201,000 Gg. The proportion of threatened mammals endemic to a
      single country represented by the 144 countries changed from 91% to 84%. Figures
      1-3 have been updated to show the correct values and map colours and the
      Supplementary Information has been updated to give the correct country codes.

PMID- 29593245
TI  - Evaluation and optimization of differentiation conditions for human primary brown
      adipocytes.
AB  - As an effective way to improve energy expenditure, increasing the mass and
      activity of brown adipose tissue (BAT) has become a promising treatment for
      obesity and its associated disorders. Many efforts have been made to promote
      brown adipogenesis and increase the thermogenic capacity of brown adipose cells
      (BACs). The present culture schemes for human BAC differentiation are mostly
      derived from white adipocyte differentiation schemes. To solve this issue, we
      compared the adipogenic and thermogenic effects of various components on human
      BAC differentiation and optimized their concentrations as well as the culture
      time for BAC differentiation. In this study, we found that the induction factors
      did not show a dose-dependent promotion of brown adipogenesis or thermogenic
      capacity. The higher differentiation levels did not inevitably result in higher
      BAT-specific gene expression levels or increased beta3-receptor agonist
      sensitivity. As an important element of culture medium, triiodothyronine was
      found to be essential for differentiation and metabolic property maintenance.
      Furthermore, compared with other reported methods, this protocol induced a
      specific intrinsic differentiation program. Our study provides not only an
      optimized method for human BAC differentiation but also a cell model with good
      differentiation and thermogenic capacity for brown adipose research.

PMID- 29593246
TI  - Emerging recombinant noroviruses identified by clinical and waste water
      screening.
AB  - Norovirus is estimated to cause 677 million annual cases of gastroenteritis
      worldwide, resulting in 210,000 deaths. As viral gastroenteritis is generally
      self-limiting, clinical samples for epidemiological studies only partially
      represent circulating noroviruses in the population and is biased towards severe
      symptomatic cases. As infected individuals from both symptomatic and asymptomatic
      cases shed viruses into the sewerage system at a high concentration, waste water
      samples are useful for the molecular epidemiological analysis of norovirus
      genotypes at a population level. Using Illumina MiSeq and Sanger sequencing, we
      surveyed circulating norovirus within Australia and New Zealand, from July 2014
      to December 2016. Importantly, norovirus genomic diversity during 2016 was
      compared between clinical and waste water samples to identify potential pandemic
      variants, novel recombinant viruses and the timing of their emergence. Although
      the GII.4 Sydney 2012 variant was prominent in 2014 and 2015, its prevalence
      significantly decreased in both clinical and waste water samples over 2016. This
      was concomitant with the emergence of multiple norovirus strains, including
      twoGII.4 Sydney 2012 recombinant viruses, GII.P4 New Orleans 2009/GII.4 Sydney
      2012 and GII.P16/GII.4 Sydney 2012, along with three other emerging strains
      GII.17, GII.P12/GII.3 and GII.P16/GII.2. This is unusual, as a single GII.4
      pandemic variant is generally responsible for 65-80% of all human norovirus
      infections at any one time and predominates until it is replaced by a new
      pandemic variant. In sumary, this study demonstrates the combined use of clinical
      and wastewater samples provides a more complete picture of norovirus circulating
      within the population.

PMID- 29593247
TI  - A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell
      malignant morphology, spread and invasion capability observed "in vivo".
AB  - Purpose of this study was the development of a 3D material to be used as
      substrate for breast cancer cell culture. We developed composite gels constituted
      by different concentrations of Alginate (A) and Matrigel (M) to obtain a
      structurally stable-in-time and biologically active substrate. Human aggressive
      breast cancer cells (i.e. MDA-MB-231) were cultured within the gels. Known the
      link between cell morphology and malignancy, cells were morphologically
      characterized and their invasiveness correlated through an innovative bioreactor
      based invasion assay. A particular type of gel (i.e. 50% Alginate, 50% Matrigel)
      emerged thanks to a series of significant results: 1. cells exhibited peculiar
      cytoskeleton shapes and nuclear fragmentation characteristic of their malignancy;
      2. cells expressed the formation of the so-called invadopodia, actin-based
      protrusion of the plasma membrane through which cells anchor to the extracellular
      matrix; 3. cells were able to migrate through the gels and attach to an
      engineered membrane mimicking the vascular walls hosted within bioreactor,
      providing a completely new 3D in vitro model of the very precursor steps of
      metastasis.

PMID- 29593249
TI  - Inside out: regenerative medicine for recessive dystrophic epidermolysis bullosa.
AB  - Epidermolysis bullosa is classified as a genodermatosis, an inherited genetic
      skin disorder that results in severe, chronic skin blistering with painful and
      life-threatening complications. Although there is currently no cure for
      epidermolysis bullosa, concurrent advances in gene and stem cell therapies are
      converging toward combinatorial therapies that hold the promise of clinically
      meaningful and lifelong improvement. Recent studies using hematopoietic stem
      cells and mesenchymal stromal/stem cells to treat epidermolysis bullosa have
      demonstrated the potential for sustained, effective management of the most severe
      cases. Furthermore, advances in the use of gene therapy and gene-editing
      techniques, coupled with the development of induced pluripotent stem cells from
      patients with epidermolysis bullosa, allow for autologous therapies derived from
      a renewable population of cells that are patient-specific. Here we describe
      emerging treatments for epidermolysis bullosa and other genodermatoses, along
      with a discussion of their benefits and limitations as effective therapies.

PMID- 29593250
TI  - Size-dependent activity and selectivity of carbon dioxide photocatalytic
      reduction over platinum nanoparticles.
AB  - Platinum nanoparticles (Pt NPs) are one of the most efficient cocatalysts in
      photocatalysis, and their size determines the activity and the selectivity of the
      catalytic reaction. Nevertheless, an in-depth understanding of the platinum's
      size effect in the carbon dioxide photocatalytic reduction is still lacking.
      Through analyses of the geometric features and electronic properties with
      variable-sized Pt NPs, here we show a prominent size effect of Pt NPs in both the
      activity and selectivity of carbon dioxide photocatalytic reduction. Decreasing
      the size of Pt NPs promotes the charge transfer efficiency, and thus enhances
      both the carbon dioxide photocatalytic reduction and hydrogen evolution reaction
      (HER) activity, but leads to higher selectivity towards hydrogen over methane.
      Combining experimental results and theoretical calculations, in Pt NPs, the
      terrace sites are revealed as the active sites for methane generation; meanwhile,
      the low-coordinated sites are more favorable in the competing HER.

PMID- 29593251
TI  - Targeting MDMX and PKCdelta to improve current uveal melanoma therapeutic
      strategies.
AB  - Uveal melanoma (UM) is the most frequent ocular cancer in adults, accounting for
      ~5% of the total melanoma incidence. Although the primary tumor is well
      treatable, patients frequently develop metastases for which no curative therapy
      exists. Highly activated protein kinase C (PKC) is a common feature of UM and has
      shown potential as therapeutic intervention for UM patients. Unfortunately, PKC
      inhibition as single treatment appears to have only limited clinical benefit.
      Combining PKC inhibition with activation of p53, which is rarely mutated in UM,
      by MDM2 inhibitors has shown promising results in vitro and in vivo. However,
      clinical studies have shown strong adverse effects of MDM2 inhibition. Therefore,
      we investigated alternative approaches to achieve similar anticancer effects, but
      with potentially less adverse effects. We studied the potential of targeting
      MDMX, an essential p53 inhibitor during embryonal development but less
      universally expressed in adult tissues compared with MDM2. Therefore, targeting
      MDMX is predicted to have less adverse effects in patients. Depletion of MDMX,
      like the pharmacological activation of p53, inhibits the survival of UM cells,
      which is enhanced in combination with PKC inhibition. Also pan-PKC inhibitors
      elicit adverse effects in patients. As the PKC family consists of 10 different
      isoforms, it could be hypothesized that targeting a single PKC isoform would have
      less adverse effects compared with a pan-PKC inhibitor. Here we show that
      specifically depleting PKCdelta inhibits UM cell growth, which can be further
      enhanced by p53 reactivation. In conclusion, our data show that the synergistic
      effects of p53 activation by MDM2 inhibition and broad spectrum PKC inhibition on
      survival of UM cells can also largely be achieved by the presumably less toxic
      combination of depletion of MDMX and targeting a specific PKC isoform, PKCdelta.

PMID- 29593253
TI  - Development, characterization and dissolution behavior of calcium-aluminoborate
      glass wasteforms to immobilize rare-earth oxides.
AB  - Calcium-aluminoborate (CAB) glasses were developed to sequester new waste
      compositions made of several rare-earth oxides generated from the pyrochemical
      reprocessing of spent nuclear fuel. Several important wasteform properties such
      as waste loading, processability and chemical durability were evaluated. The
      maximum waste loading of the CAB compositions was determined to be ~56.8 wt%.
      Viscosity and the electrical conductivity of the CAB melt at 1300  degrees C were
      7.817 Pa.s and 0.4603 S/cm, respectively, which satisfies the conditions for
      commercial cold-crucible induction melting (CCIM) process. Addition of rare-earth
      oxides to CAB glasses resulted in dramatic decreases in the elemental releases of
      B and Ca in aqueous dissolution experiments. Normalized elemental releases from
      product consistency standard chemical durability test were <3.62.10-5 g.m-2 for
      Nd, 0.009 g.m-2 for Al, 0.067 g.m-2 for B and 0.073 g.m-2 for Ca (at 90, after 7
      days, for SA/V = 2000m-1); all meet European and US regulation limits. After 20 d
      of dissolution, a hydrated alteration layer of ~ 200-nm-thick, Ca-depleted and Nd
      rich, was formed at the surface of CAB glasses with 20 mol% Nd2O3 whereas
      boehmite [AlO(OH)] secondary crystalline phases were formed in pure CAB glass
      that contained no Nd2O3.

PMID- 29593252
TI  - Dedicated photoreceptor pathways in Drosophila larvae mediate navigation by
      processing either spatial or temporal cues.
AB  - To integrate changing environmental cues with high spatial and temporal
      resolution is critical for animals to orient themselves. Drosophila larvae show
      an effective motor program to navigate away from light sources. How the larval
      visual circuit processes light stimuli to control navigational decision remains
      unknown. The larval visual system is composed of two sensory input channels,
      Rhodopsin5 (Rh5) and Rhodopsin6 (Rh6) expressing photoreceptors (PRs). We here
      characterize how spatial and temporal information are used to control navigation.
      Rh6-PRs are required to perceive temporal changes of light intensity during head
      casts, while Rh5-PRs are required to control behaviors that allow navigation in
      response to spatial cues. We characterize how distinct behaviors are modulated
      and identify parallel acting and converging features of the visual circuit.
      Functional features of the larval visual circuit highlight the principle of how
      early in a sensory circuit distinct behaviors may be computed by partly
      overlapping sensory pathways.

PMID- 29593254
TI  - Phylogenetic analysis and virulence determinant of the host-adapted
      Staphylococcus aureus lineage ST188 in China.
AB  - Staphylococcus aureus (S. aureus) is an important pathogen of humans and
      livestock species, but an understanding of the clonal distribution of S. aureus
      causing different host-species infections in the same geographical environment
      and within the same period is lacking. By characterizing infections caused by S.
      aureus in bovine, pediatric, and adult patients in Shanghai, China, between 2012
      and 2014, we identified methicillin-sensitive S. aureus (MSSA) ST188 as the major
      lineage causing infections in multiple host species. Whole-genome sequencing and
      phenotypic analyses demonstrated that ST188 might evolve from livestock, and
      there was no significant genomic or virulence difference between ST188 isolated
      from livestock and humans. The virulence of ST188 is related to its adhesion and
      nasal colonization ability. This result is in accord with the strong epithelial
      cell adhesion and biofilm formation properties of ST188. Furthermore, the
      adhesion- and biofilm-formation-related genes are present in multiple copies and
      exhibit significantly increased expression in ST188. In conclusion, S. aureus
      ST188 is the major lineage causing human and livestock infections in Shanghai,
      China. Due to its high expression of the factors associated with bacterial
      adhesion and biofilm formation, ST188 has the ability to colonize and infect
      different host species.

PMID- 29593255
TI  - Stress-induced phosphoprotein 1 acts as a scaffold protein for glycogen synthase
      kinase-3 beta-mediated phosphorylation of lysine-specific demethylase 1.
AB  - Stress-induced phosphoprotein 1 (STIP1)-a co-chaperone of heat shock proteins
      promotes cell proliferation and may act as an oncogenic factor. Similarly,
      glycogen synthase kinase-3 beta (GSK3beta)-mediated phosphorylation of lysine
      specific demethylase 1 (LSD1)-an epigenetic regulator-can contribute to the
      development of an aggressive cell phenotype. Owing to their ability to tether
      different molecules into functional complexes, scaffold proteins have a key role
      in the regulation of different signaling pathways in tumorigenesis. Here, we show
      that STIP1 acts as a scaffold promoting the interaction between LSD1 and
      GSK3beta. Specifically, the TPR1 and TPR2B domains of STIP1 are capable of
      binding with the AOL domain of LSD1, whereas the TPR2A and TPR2B domains of STIP1
      interact with the kinase domain of GSK3beta. We also demonstrate that STIP1 is
      required for GSK3beta-mediated LSD1 phosphorylation, which promoted LSD1
      stability and enhanced cell proliferation. After transfection of cancer cells
      with double-mutant (S707A/S711A) LSD1, subcellular localization analysis revealed
      that LSD1 was translocated from the nucleus to the cytoplasm. In vitro
      experiments also showed that the LSD1 inhibitor SP2509 and the GSK3beta inhibitor
      LY2090314 acted synergistically to induce cancer cell death. Finally, the
      immunohistochemical expression of STIP1 and LSD1 showed a positively correlation
      in human cancer specimens. In summary, our data provide mechanistic insights into
      the role of STIP1 in human tumorigenesis by showing that it serves as a scaffold
      for GSK3beta-mediated LSD1 phosphorylation. The combination of LSD1 and GSK3beta
      inhibitors may exert synergistic antitumor effects and deserves further scrutiny
      in preclinical studies.

PMID- 29593256
TI  - Microencephaly in fetal piglets following in utero inoculation of Zika virus.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus that became associated with
      microcephaly in newborns and Guillain-Barre syndrome in adults after its
      emergence in the Pacific and the Americas in 2015. Newly developed rodent and
      nonhuman primate models have already revealed important insights into ZIKV
      induced neuropathology. Nonhuman primates are phylogenetically closely related to
      humans and are therefore preferred human surrogates in ZIKV research. However,
      the use of nonhuman primates, particularly during gestation, raises ethical
      issues. Considering that pigs also share many anatomical and physiological
      features with humans, this species may be an attractive alternative human
      surrogate for ZIKV research. Here, we inoculated 20 porcine fetuses in utero and
      assessed the effect of ZIKV on brain development 4 weeks later. All inoculated
      fetuses presented mild to severe neuropathology, characterized by a depletion of
      neurons in the cerebral cortex. In most cases, neuronal depletion was confined to
      specific cerebral lobes without affecting brain size, whereas in severe cases a
      more generalized depletion resulted in microencephaly. Although the virus was
      widespread in the sows' placenta at the time of necropsy only low levels of viral
      RNA were detected in fetal brain samples, thereby preventing the identification
      of primary target cells. Our findings suggest that pigs can be used to study ZIKV
      induced neurodevelopmental defects as currently observed in human neonates,
      varying from stunted brain growth to localized cortical neuronal depletion in the
      absence of major macroscopic abnormalities.

PMID- 29593257
TI  - Lung Topology Characteristics in patients with Chronic Obstructive Pulmonary
      Disease.
AB  - Quantitative features that can currently be obtained from medical imaging do not
      provide a complete picture of Chronic Obstructive Pulmonary Disease (COPD). In
      this paper, we introduce a novel analytical tool based on persistent homology
      that extracts quantitative features from chest CT scans to describe the geometric
      structure of the airways inside the lungs. We show that these new radiomic
      features stratify COPD patients in agreement with the GOLD guidelines for COPD
      and can distinguish between inspiratory and expiratory scans. These CT
      measurements are very different to those currently in use and we demonstrate that
      they convey significant medical information. The results of this study are a
      proof of concept that topological methods can enhance the standard methodology to
      create a finer classification of COPD and increase the possibilities of more
      personalized treatment.

PMID- 29593258
TI  - Oxygen radical character in group 11 oxygen fluorides.
AB  - Transition metal complexes bearing terminal oxido ligands are quite common, yet
      group 11 terminal oxo complexes remain elusive. Here we show that excited coinage
      metal atoms M (M = Au, Ag, Cu) react with OF2 to form hypofluorites FOMF and
      group 11 oxygen metal fluorides OMF2, OAuF and OAgF. These compounds have been
      characterized by IR matrix-isolation spectroscopy in conjunction with state-of
      the-art quantum-chemical calculations. The oxygen fluorides are formed by
      photolysis of the initially prepared hypofluorites. The linear molecules OAgF and
      OAuF have a 3Sigma - ground state with a biradical character. Two unpaired
      electrons are located mainly at the oxygen ligand in antibonding O-M pi*
      orbitals. For the 2B2 ground state of the OMIIIF2 compounds only an O-M single
      bond arises and a significant spin-density contribution was found at the oxygen
      atom as well.

PMID- 29593260
TI  - DDR signature to predict response to ICI.

PMID- 29593261
TI  - PET imaging reveals EGFR mutation status.

PMID- 29593259
TI  - Wild birds in Chile Harbor diverse avian influenza A viruses.
AB  - While the circulation of avian influenza viruses (IAV) in wild birds in the
      northern hemisphere has been well documented, data from South America remain
      sparse. To address this gap in knowledge, we undertook IAV surveillance in wild
      birds in parts of Central and Northern Chile between 2012 and 2015. A wide
      diversity of hemagglutinin (HA) and neuraminidase (NA) subtypes were identified
      and 16 viruses were isolated including low pathogenic H5 and H7 strains, making
      this the largest and most diverse collection of Chilean avian IAVs to date.
      Unlike IAVs isolated from wild birds in other South American countries where the
      genes were most like viruses isolated from wild birds in either North America or
      South America, the Chilean viruses were reassortants containing genes like
      viruses isolated from both continents. In summary, our studies demonstrate that
      genetically diverse avian IAVs are circulating in wild birds in Chile
      highlighting the need for further investigation in this understudied area of the
      world.

PMID- 29593262
TI  - Synthesis of AgN5 and its extended 3D energetic framework.
AB  - The pentazolate anion, as a polynitrogen species, holds great promise as a high
      energy density material for explosive or propulsion applications. Designing
      pentazole complexes that contain minimal non-energetic components is desirable in
      order to increase the material's energy density. Here, we report a solvent-free
      pentazolate complex, AgN5, and a 3D energetic-framework, [Ag(NH3)2]+[Ag3(N5)4]-,
      constructed from silver and cyclo-N5-. The complexes are stable up to 90  degrees
      C and only Ag and N2 are observed as the final decomposition products. Efforts to
      isolate pure AgN5 were unsuccessful due to partial photolytical and/or thermal
      decomposition to AgN3. Convincing evidence for the formation of AgN5 as the
      original reaction product is presented. The isolation of a cyclo-N5- complex,
      devoid of stabilizing molecules and ions, such as H2O, H3O+, and NH4+,
      constitutes a major advance in pentazole chemistry.

PMID- 29593263
TI  - Detection of Coccidioides posadasii from xerophytic environments in Venezuela
      reveals risk of naturally acquired coccidioidomycosis infections.
AB  - A wide range of mammals are susceptible to infection by the fungal species
      Coccidioides immitis and C. posadasii. In humans, 60% of infections are
      asymptomatic; however, certain patients may develop a severe and deep systemic
      mycosis called coccidioidomycosis. Genetic analysis suggests that the majority of
      clinical isolates recovered from South America are C. posadasii; however, little
      is known about the prevalence, species distribution, and ecological factors that
      favor the occurrence of this pathogen in those areas. By using a combined
      quantitative polymerase chain reaction (qPCR)-based approach and mycobiome
      amplicon sequencing, we provide evidence that at least two genotypes of C.
      posadasii are found in the xerophytic environment in Venezuela. We detected a
      3806-fold range in the amount of Coccidioides DNA when comparing among the
      sampled locations, which indicates that human exposure risk is variable, and is
      one critical factor for disease manifestation. We identified fungal communities
      that are correlated with a higher prevalence of C. posadasii, suggesting that a
      combination of specific microbes and a xeric microenvironment may favor the
      growth of Coccidioides in certain locations. Moreover, we discuss the use of a
      combinatorial approach, using both qPCR and deep-sequencing methods to assess and
      monitor fungal pathogen burden at outbreak sources.

PMID- 29593264
TI  - Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA
      accumulation and SASP in senescent cells.
AB  - Accumulating evidence indicates that the senescence-associated secretory
      phenotype (SASP) contributes to many aspects of physiology and disease. Thus,
      controlling the SASP will have tremendous impacts on our health. However, our
      understanding of SASP regulation is far from complete. Here, we show that
      cytoplasmic accumulation of nuclear DNA plays key roles in the onset of SASP.
      Although both DNase2 and TREX1 rapidly remove the cytoplasmic DNA fragments
      emanating from the nucleus in pre-senescent cells, the expression of these DNases
      is downregulated in senescent cells, resulting in the cytoplasmic accumulation of
      nuclear DNA. This causes the aberrant activation of cGAS-STING cytoplasmic DNA
      sensors, provoking SASP through induction of interferon-beta. Notably, the
      blockage of this pathway prevents SASP in senescent hepatic stellate cells,
      accompanied by a decline of obesity-associated hepatocellular carcinoma
      development in mice. These findings provide valuable new insights into the roles
      and mechanisms of SASP and possibilities for their control.

PMID- 29593265
TI  - Lymphotoxin alpha fine-tunes T cell clonal deletion by regulating thymic entry of
      antigen-presenting cells.
AB  - Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of
      autoreactive thymocytes. Although dendritic cells (DC) reinforce this process by
      transporting innocuous peripheral self-antigens, the mechanisms that control
      their thymic entry remain unclear. Here we show that mTEC-CD4+ thymocyte
      crosstalk regulates the thymus homing of SHPS-1+ conventional DCs (cDC),
      plasmacytoid DCs (pDC) and macrophages. This homing process is controlled by
      lymphotoxin alpha (LTalpha), which negatively regulates CCL2, CCL8 and CCL12
      chemokines in mTECs. Consequently, Ltalpha-deficient mice have increased
      expression of these chemokines that correlates with augmented classical NF-kappaB
      subunits and increased thymic recruitment of cDCs, pDCs and macrophages. This
      enhanced migration depends mainly on the chemokine receptor CCR2, and increases
      thymic clonal deletion. Altogether, this study identifies a fine-tuning mechanism
      of T cell repertoire selection and paves the way for therapeutic interventions to
      treat autoimmune disorders.

PMID- 29593266
TI  - Compositional heterogeneity near the base of the mantle transition zone beneath
      Hawaii.
AB  - Global seismic discontinuities near 410 and 660 km depth in Earth's mantle are
      expressions of solid-state phase transitions. These transitions modulate thermal
      and material fluxes across the mantle and variations in their depth are often
      attributed to temperature anomalies. Here we use novel seismic array analysis of
      SS waves reflecting off the 410 and 660 below the Hawaiian hotspot. We find
      amplitude-distance trends in reflectivity that imply lateral variations in
      wavespeed and density contrasts across 660 for which thermodynamic modeling
      precludes a thermal origin. No such variations are found along the 410. The
      inferred 660 contrasts can be explained by mantle composition varying from
      average (pyrolitic) mantle beneath Hawaii to a mixture with more melt-depleted
      harzburgite southeast of the hotspot. Such compositional segregation was
      predicted, from petrological and numerical convection studies, to occur near hot
      deep mantle upwellings like the one often invoked to cause volcanic activity on
      Hawaii.

PMID- 29593267
TI  - Gold Nanorods as Visual Sensing Platform for Chiral Recognition with Naked Eyes.
AB  - Chirality plays a key role in modern science and technology. Here, we report a
      simple and effective sensing platform for visual chiral recognition of
      enantiomers. In this sensing platform, gold nanorods (AuNRs) prepared through a
      common synthesis route are used as colorimetric probes for visual recognition of
      glutamine (Gln) enantiomers. D-Gln could rapidly induce the aggregation of AuNRs,
      thereby resulting in appreciable blue-to-gray color change of AuNRs solution;
      however, L-Gln could not induce color change of AuNRs. This distinct color change
      can be easily distinguished by the naked eyes; as a result, a visual method of
      chiral recognition was suggested. The method was applied to determine the
      enantiometric excess of D-Gln through the whole range of -100% ~ 100%. The chiral
      assay can be performed with a simple UV-vis spectrometer or the naked eyes.
      Notably, the AuNRs do not need any chiral labeling or modification, and the
      chiral recognition is based on the inherent chirality of AuNRs. This chiral assay
      method is simple, sensitive, cheap and easy to operate. This study is the first
      example using AuNRs for direct visual recognition of enantiomers, and will open
      new opportunity to construct more chiral recognition methods for some important
      compounds.

PMID- 29593269
TI  - Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in
      normal tension glaucoma and healthy individuals: a Pilot study.
AB  - The purpose of this prospective, case control study was to investigate the
      differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy
      (LSFG) between Caucasian patients with normal tension glaucoma and healthy
      subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal
      tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In
      the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the
      investigations. Measurement of optic nerve head blood flow was performed with
      LSFG. The mean blur rate was obtained for different vascular compartments of the
      optic nerve head. Parameters for the characterization of pulse-waveform of the
      mean blur rate were calculated. It was shown that the mean blur rate was
      significantly lower in the glaucoma group compared to the control group (P <
      0.001). The significant differences in the pulse-waveform parameters blow out
      time (P = 0.028) and flow acceleration time index (P < 0.001) indicate a flatter
      curve in NTG patients. In conclusion, LSFG can detect differences in optic nerve
      head blood flow between eyes with normal tension glaucoma and healthy eyes.

PMID- 29593268
TI  - A complex epistatic network limits the mutational reversibility in the influenza
      hemagglutinin receptor-binding site.
AB  - The hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses
      is critical for attachment to host cells, which imposes a functional constraint
      on its natural evolution. On the other hand, being part of the major antigenic
      sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the
      immune system. From large-scale mutagenesis experiments, we here show that
      several of the natural RBS substitutions become integrated into an extensive
      epistatic network that prevents substitution reversion. X-ray structural analysis
      reveals the mechanistic consequences as well as changes in the mode of receptor
      binding. Further studies are necessary to elucidate whether such entrenchment
      limits future options for immune escape or adversely affect long-term viral
      fitness.

PMID- 29593270
TI  - Sample-Index Misassignment Impacts Tumour Exome Sequencing.
AB  - Sample pooling enabled by dedicated indexes is a common strategy for cost
      effective and robust high-throughput sequencing. Index misassignment leading to
      mutual contamination between pooled samples has however been described as a
      general problem of the latest Illumina sequencing instruments utilizing exclusion
      amplification. Using real-life data from multiple tumour sequencing projects, we
      demonstrate that index misassignment can induce artefactual variant calls closely
      resembling true, high-quality somatic variants. These artefactual calls
      potentially impact cancer applications utilizing low allelic frequencies, such as
      in clonal analysis of tumours. We discuss the available countermeasures with an
      emphasis on improved library indexing methods, and provide software that can
      assist in the identification of variants that may be consequences of index
      misassignment.

PMID- 29593271
TI  - Evaluating the efficacy of a landscape scale feral cat control program using
      camera traps and occupancy models.
AB  - The impact of introduced predators is a major factor limiting survivorship and
      recruitment of many native Australian species. In particular, the feral cat and
      red fox have been implicated in range reductions and population declines of many
      conservation dependent species across Australia, including ground-nesting birds
      and small to medium-sized mammals. The impact of predation by feral cats since
      their introduction some 200 years ago has altered the structure of native fauna
      communities and led to the development of landscape-scale threat abatement via
      baiting programs with the feral cat bait, Eradicat. Demonstrating the
      effectiveness of broad-scale programs is essential for managers to fine tune
      delivery and timing of baiting. Efficacy of feral cat baiting at the Fortescue
      Marsh in the Pilbara, Western Australia was tested using camera traps and
      occupancy models. There was a significant decrease in probability of site
      occupancy in baited sites in each of the five years of this study, demonstrating
      both the effectiveness of aerial baiting for landscape-scale removal of feral
      cats, and the validity of camera trap monitoring techniques for detecting changes
      in feral cat occupancy during a five-year baiting program.

PMID- 29593272
TI  - Aftershock sequences and seismic-like organization of acoustic events produced by
      a single propagating crack.
AB  - Brittle fractures of inhomogeneous materials like rocks, concrete, or ceramics
      are of two types: Nominally brittle and driven by the propagation of a single
      dominant crack or quasi-brittle and resulting from the accumulation of many
      microcracks. The latter goes along with acoustic noise, whose analysis has
      revealed that events form aftershock sequences obeying characteristic laws
      reminiscent of those in seismology. Yet, their origin lacks explanation. Here we
      show that such a statistical organization is not only specific to the multi
      cracking situations of quasi-brittle failure and seismology, but also rules the
      acoustic events produced by a propagating crack. This simpler situation has
      permitted us to relate these laws to the overall scale-free distribution of inter
      event time and energy and to uncover their selection by the crack speed. These
      results provide a comprehensive picture of how acoustic events are organized upon
      material failure in the most fundamental of fracture states: single propagating
      cracks.

PMID- 29593273
TI  - Nuclear disarmament verification via resonant phenomena.
AB  - Nuclear disarmament treaties are not sufficient in and of themselves to
      neutralize the existential threat of the nuclear weapons. Technologies are
      necessary for verifying the authenticity of the nuclear warheads undergoing
      dismantlement before counting them toward a treaty partner's obligation. Here we
      present a concept that leverages isotope-specific nuclear resonance phenomena to
      authenticate a warhead's fissile components by comparing them to a previously
      authenticated template. All information is encrypted in the physical domain in a
      manner that amounts to a physical zero-knowledge proof system. Using Monte Carlo
      simulations, the system is shown to reveal no isotopic or geometric information
      about the weapon, while readily detecting hoaxing attempts. This nuclear
      technique can dramatically increase the reach and trustworthiness of future
      nuclear disarmament treaties.

PMID- 29593274
TI  - On the nucleus composition during isothermal alloy solidification.
AB  - Accurate determination of the nucleus composition during isothermal alloy
      solidification still represents a great challenge nowadays. In this paper, a
      kinetic scheme was added to the Hillert-Rettenmayr thermodynamic analysis of the
      deviation from local equilibrium at migrating phase interfaces. A so-called
      interface permeability was introduced to account for the unambiguous
      determination of the energy dissipation of the solute rearrangement at the liquid
      solid interface and the driving force for interface movement, from which the
      nucleus composition can be then evaluated. After benchmark test, a pragmatic
      nucleation model for solidification was also proposed, and applied in three
      dimensional phase-field simulations of nucleation and subsequent dendritic growth
      during isothermal solidification process in one hypothetic Al-Si alloy. Moreover,
      the influence of the interface permeability on nucleation rate was fully
      discussed by exploring its effect on the initial nucleus components and the
      corresponding nucleation driving force.

PMID- 29593275
TI  - Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen
      Candida auris.
AB  - Candida auris was first described in 2009, and it has since caused nosocomial
      outbreaks, invasive infections, and fungaemia across at least 19 countries on
      five continents. An outbreak of C. auris occurred in a specialized cardiothoracic
      London hospital between April 2015 and November 2016, which to date has been the
      largest outbreak in the UK, involving a total of 72 patients. To understand the
      genetic epidemiology of C. auris infection both within this hospital and within a
      global context, we sequenced the outbreak isolate genomes using Oxford Nanopore
      Technologies and Illumina platforms to detect antifungal resistance alleles and
      reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in
      the India/Pakistan clade, demonstrating an Asian origin; the outbreak showed
      similar genetic diversity to that of the entire clade, and limited local
      spatiotemporal clustering was observed. One isolate displayed resistance to both
      echinocandins and 5-flucytosine; the former was associated with a serine to
      tyrosine amino acid substitution in the gene FKS1, and the latter was associated
      with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations
      add to a growing body of research on multiple antifungal drug targets in this
      organism. Multiple differential episodic selection of antifungal resistant
      genotypes has occurred within a genetically heterogenous population across this
      outbreak, creating a resilient pathogen and making it difficult to define local
      scale patterns of transmission and implement outbreak control measures.

PMID- 29593276
TI  - Fluorescent label-free quantitative detection of nano-sized bioparticles using a
      pillar array.
AB  - Disease diagnostics requires detection and quantification of nano-sized
      bioparticles including DNA, proteins, viruses, and exosomes. Here, a fluorescent
      label-free method for sensitive detection of bioparticles is explored using a
      pillar array with micrometer-sized features in a deterministic lateral
      displacement (DLD) device. The method relies on measuring changes in size and/or
      electrostatic charges of 1 um polymer beads due to the capture of target
      bioparticles on the surface. These changes can be sensitively detected through
      the lateral displacement of the beads in the DLD array, wherein the lateral
      shifts in the output translates to a quantitative measurement of bioparticles
      bound to the bead. The detection of albumin protein and nano-sized polymer
      vesicles with a concentration as low as 10 ng mL-1 (150 pM) and 3.75 MUg mL-1,
      respectively, is demonstrated. This label-free method holds potential for point
      of-care diagnostics, as it is low-cost, fast, sensitive, and only requires a
      standard laboratory microscope for detection.

PMID- 29593277
TI  - Prevalence and serogroup changes of Neisseria meningitidis in South Korea, 2010
      2016.
AB  - Determination of the major serogroups is an important step for establishing a
      vaccine programme and management strategy targeting Neisseria meningitidis. From
      April 2010 to November 2016, a total of 25 N. meningitidis isolates were
      collected in South Korea, in collaboration with the Korean Society of Clinical
      Microbiology. Among isolates, 19 isolates were recovered from blood and/or
      cerebrospinal fluid (CSF) in 46 patients who suffered from invasive meningococcal
      disease (IMD), and six isolates were found in sputum or the throat. The most
      common serogroup was serogroup B (overall, 36%, n = 9/25; IMD, 37%, n = 7/19),
      which was isolated in every year of the research period except for 2011. There
      were five serogroup W isolates recovered from patients in military service. W was
      no longer isolated after initiation of a vaccine programme for military trainees,
      but serogroup B caused meningitis in an army recruit training centre in 2015. In
      MLST analysis, 14 sequence types were found, and all isolates belonging to W
      showed the same molecular epidemiologic characteristics (W:P1.5-1, 2-2:F3-9:ST
      8912). All isolates showed susceptibility to ceftriaxone, meropenem,
      ciprofloxacin, minocycline, and rifampin; however, the susceptibility rates to
      penicillin and ampicillin for isolates with W and C capsules were 22% and 30%,
      respectively.

PMID- 29593278
TI  - Determining the effect of different environmental conditions on Ebola virus
      viability in clinically relevant specimens.
AB  - In 2013-2016, West Africa experienced the largest and longest Ebola virus disease
      outbreak ever documented. The wide geographic spread and magnitude of the
      outbreak often limited the timely and rapid testing of diagnostic samples from
      patients with suspected Ebola virus disease, raising questions regarding the
      optimal storage and shipping conditions of clinically relevant specimens,
      including EDTA-whole blood, plasma, capillary blood, urine and seminal fluid
      (associated with sexual transmission of the Ebola virus after recovery from the
      disease). Therefore, the aim of our study was to identify the extent to which
      storage temperature and clinical specimen type influence Ebola virus viability.
      Virus infectivity was determined using a fluorescent focus-forming assay. In our
      study, we show that Ebola virus was the most stable in EDTA-whole blood and
      plasma samples, whereas rapid decay of infectivity was observed in simulated
      capillary blood, urine and semen samples, especially when these samples were
      stored at higher temperatures. The analysis of variance results demonstrated that
      both temperature and clinical specimen type have significant effects on virus
      viability, whereas donor differences were not observed. Repeated freeze and thaw
      cycles of the samples also had a notable impact on virus viability in EDTA-whole
      blood and urine. Due to the rapid temperature- and specimen-dependent degradation
      of the virus observed here, our study highlights the importance of proper
      clinical sample storage at low temperatures during transportation and laboratory
      analysis.

PMID- 29593279
TI  - Asymmetric electric field screening in van der Waals heterostructures.
AB  - A long-standing challenge facing the combination of two-dimensional crystals into
      heterojunction is the unknown effect of mixing layer of different electronic
      properties (semiconductors, metals, insulators) on the screening features of the
      fabricated device platforms including their functionality. Here we use a
      compelling set of theoretical and experimental techniques to elucidate the
      intrinsic dielectric screening properties of heterostructures formed by MoS2 and
      graphene layers. We experimentally observed an asymmetric field screening effect
      relative to the polarization of the applied gate bias into the surface.
      Surprisingly, such behavior allows selection of the electronic states that screen
      external fields, and it can be enhanced with increasing of the number of layers
      of the semiconducting MoS2 rather than the semi-metal. This work not only
      provides unique insights on the screening properties of a vast amount of
      heterojunction fabricated so far, but also uncovers the great potential of
      controlling a fundamental property for device applications.

PMID- 29593280
TI  - Multi-nanolayered VO2/Sapphire Thin Film via Spinodal Decomposition.
AB  - Coating of VO2-based thin film has been extensively studied for fabricating
      energy-saving smart windows. One of the most efficient ways for fabricating high
      performance films is to create multi-nanolayered structure. However, it has been
      highly challenge to make such layers in the VO2-based films using conventional
      methods. In this work, a facile two-step approach is established to fabricate
      multilayered VO2-TiO2 thin films. We first deposited the amorphous thin films
      upon sputtering, and then anneal them to transform the amorphous phase into
      alternating Ti- and V-rich multilayered nanostructure via a spinodal
      decomposition mechanism. In particular, we take advantage of different sapphire
      substrate planes (A-plane (11-20), R-plane (1-102), C-plane (0001), and M-plane
      (10-10)) to achieve different decomposition modes. The new approach has made it
      possible to tailoring the microstructure of the thin films for optimized
      performances by controlling the disorder-order transition in terms of both
      kinetic and thermodynamic aspects. The derived thin films exhibit superior
      optical modulation upon phase transition, significantly reduced transition
      temperature and hysteresis loop width, and high degradation resistance, these
      improvements indicate a high potential to be used for fabricating the next
      generation of energy saving smart windows.

PMID- 29593281
TI  - Long-term effects of low calcium dialysates on the serum calcium levels during
      maintenance hemodialysis treatments: A systematic review and meta-analysis.
AB  - Hypercalcemia and hyperparathyroidism in patients receiving maintenance
      hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and
      mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium
      (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal
      concentration remains controversial. Here, we conducted a systematic review and a
      meta-analysis of seven randomized controlled trials examining a total of 622
      patients to investigate the optimal concentration for MHD for 6 months or longer.
      The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly
      lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52
      mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38),
      respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three
      studies showed that a low concentration was preferred for lowering arterial
      calcifications or atherosclerosis in different arteries, but one study showed
      that coronary arterial calcifications increased with a low concentration. Two
      studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed
      that a dialysate with a low Ca concentration lowered the serum Ca levels in
      patients receiving long-term MHD, but further studies are needed to determine the
      optimal Ca concentration in terms of CVD and MBD.

PMID- 29593282
TI  - Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL
      expression.
AB  - Genomic loss of 5-hydroxymethylcytosine (5hmC) accompanies malignant cellular
      transformation in breast cancer. Vitamin C serves as a cofactor for TET
      methylcytosine dioxygenases to increase 5hmC generation. Here we show that the
      transcription of SVCT2, a major vitamin C transporter, was decreased in human
      breast cancers (113 cases) compared to normal breast tissues from the same
      patients. A decreased SVCT2 expression was also observed in breast cancer cell
      lines. Treatment with vitamin C (100 MUM) increased the 5hmC content in MDA-MB
      231 breast cancer cells and markedly altered the transcriptome. The vitamin C
      treatment induced apoptosis in MDA-MB-231 cells, which was verified in two
      additional breast cancer cell lines. This pro-apoptotic effect of vitamin C
      appeared to be mediated by TRAIL, a known apoptosis inducer. Vitamin C
      upregulated TRAIL transcripts (2.3-fold increase) and increased TRAIL protein
      levels. The upregulation of TRAIL by vitamin C was largely abolished by siRNAs
      targeting TETs and anti-TRAIL antibody abrogated the induction of apoptosis.
      Furthermore, the apoptosis promoted by vitamin C was associated with Bax and
      caspases activation, Bcl-xL sequestration, and cytochrome c release. Taken
      together, these results suggest a potential role of physiological doses of
      vitamin C in breast cancer prevention and treatment.

PMID- 29593285
TI  - Vascular disease: Reduction in major adverse limb events in the COMPASS trial.

PMID- 29593284
TI  - Cementoin-SLPI fusion protein binds to human monocytes and epithelial cells and
      shows higher biological activity than SLPI.
AB  - Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide
      that blocks the activity of serine proteases, primarily the neutrophil elastase.
      In an attempt to direct the activity of SLPI on inflamed sites, a chimera
      consisting of the transglutaminase II substrate domain of trappin 2 (cementoin),
      and the mature SLPI protein was constructed. Cell attachment and biological
      activity were compared between SLPI and this chimera. By using whole cell ELISA,
      fluorescence microscopy and flow cytometry assays we observed that the cementoin
      SLPI fusion protein (FP) but not SLPI attached to a human lung epithelial cell
      line and monocytes. A maximum attachment was achieved 15 min after FP was added
      to the cell cultures. In an elastase activity assay, we observed that FP retained
      its antiprotease activity and that at equimolar amount of proteins, FP was more
      efficient than SLPI in the inhibition. Both, FP and SLPI inhibits IL-2-induced
      lymphocyte proliferation, however, lower amounts of FP were required to achieve
      this inhibition. Furthermore, FP binds to mycobacteria and maintained the
      bactericidal activity observed for SLPI. Overall, these results show that this
      new chimera is able to attach to the cell surfaces retaining and improving some
      biological activities described for SLPI.

PMID- 29593283
TI  - Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development
      to overcome immune surveillance.
AB  - Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is
      tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid
      cells can impair tumor immunity. As myeloid cells and conventional dendritic
      cells (cDCs) are derived from the same progenitors, we postulated that
      myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes
      human CD141+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by
      stimulating CD8+ T-cell responses. Here, to understand how cDC1 development
      changes during tumor progression, we investigated cDC bone marrow progenitors. We
      found localized breast and pancreatic cancers induce systemic decreases in cDC1s
      and their progenitors. Mechanistically, tumor-produced granulocyte-stimulating
      factor downregulates interferon regulatory factor-8 in cDC progenitors, and thus
      results in reduced cDC1 development. Tumor-induced reductions in cDC1 development
      impair anti-tumor CD8+ T-cell responses and correlate with poor patient outcomes.
      These data suggest immune surveillance can be impaired by tumor-induced
      alterations in cDC development.

PMID- 29593286
TI  - Hypertension: Hypertension intervention at the barbershop.

PMID- 29593287
TI  - Cardioprotection: SGLT2 blockers in T2DM.

PMID- 29593288
TI  - Developmental biology: Early heart decisions.

PMID- 29593289
TI  - Computer simulation study of early bacterial biofilm development.
AB  - Most bacteria form organized sessile communities, known as biofilms. Their
      ubiquity and relevance have stimulated the development of efficient mathematical
      models able to predict biofilm evolution and characteristics at different
      conditions. Here we present a study of the early stages of bacterial biofilm
      formation modeled by means of individual cell-based computer simulation.
      Simulation showed that clusters with different degrees of internal and
      orientational order were formed as a function of the aspect ratio of the
      individual particles and the relation between the diffusion and growth rates.
      Analysis of microscope images of early biofilm formation by the Gram-negative
      bacterium Pseudomonas putida at varying diffusion rates revealed a good
      qualitative agreement with the simulation results. Our model is a good predictor
      of microcolony morphology during early biofilm development, showing that the
      competition between diffusion and growth rates is a key aspect in the formation
      of stable biofilm microcolonies.

PMID- 29593290
TI  - Methane stimulates massive nitrogen loss from freshwater reservoirs in India.
AB  - The fate of the enormous amount of reactive nitrogen released to the environment
      by human activities in India is unknown. Here we show occurrence of seasonal
      stratification and generally low concentrations of dissolved inorganic combined
      nitrogen, and high molecular nitrogen (N2) to argon ratio, thus suggesting
      seasonal loss to N2 in anoxic hypolimnia of several dam-reservoirs. However, 15N
      experiments yielded low rates of denitrification, anaerobic ammonium oxidation
      and dissimilatory nitrate reduction to ammonium-except in the presence of methane
      (CH4) that caused ~12-fold increase in denitrification. While nitrite-dependent
      anaerobic methanotrophs belonging to the NC10 phylum were present, previously
      considered aerobic methanotrophs were far more abundant (up to 13.9%) in anoxic
      hypolimnion. Methane accumulation in anoxic freshwater systems seems to
      facilitate rapid loss of reactive nitrogen, with generally low production of
      nitrous oxide (N2O), through widespread coupling between methanotrophy and
      denitrification, potentially mitigating eutrophication and emissions of CH4 and
      N2O to the atmosphere.

PMID- 29593291
TI  - Structural insights into the RNA methyltransferase domain of METTL16.
AB  - N6-methyladenosine (m6A) is an abundant modification in messenger RNA and
      noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16
      (METTL16) is a recently confirmed m6A RNA methyltransferase that methylates U6
      spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1
      (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X
      ray crystal structures of the N-terminal methyltransferase domain (residues 1
      291) of human METTL16 (METTL16_291): an apo structure at 1.9 A resolution and a
      post-catalytic S-adenosylhomocysteine-bound complex at 2.1 A resolution. The
      structures revealed a highly conserved Rossmann fold that is characteristic of
      Class I S-adenosylmethionine-dependent methyltransferases and a large, positively
      charged groove. This groove likely represents the RNA-binding site and it
      includes structural elements unique to METTL16. In-depth analysis of the active
      site led to a model of the methyl transfer reaction catalyzed by METTL16. In
      contrast to the major m6A methyltransferase heterodimer METTL3/METTL14, full
      length METTL16 forms a homodimer and METTL16_291 exists as a monomer based on
      size-exclusion chromatography. A native gel-shift assay shows that METTL16 binds
      to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not. Our results
      provide insights into the molecular structure of METTL16, which is distinct from
      METTL3/METTL14.

PMID- 29593292
TI  - A globally-distributed alien invasive species poses risks to United States
      imperiled species.
AB  - In the midst of Earth's sixth mass extinction event, non-native species are a
      driving factor in many imperiled species' declines. One of the most widespread
      and destructive alien invasive species in the world, wild pigs (Sus scrofa)
      threaten native species through predation, habitat destruction, competition, and
      disease transmission. We show that wild pigs co-occur with up to 87.2% of
      imperiled species in the contiguous U.S. identified as susceptible to their
      direct impacts, and we project increases in both the number of species at risk
      and the geographic extent of risks by 2025. Wild pigs may therefore present a
      severe threat to U.S. imperiled species, with serious implications for management
      of at-risk species throughout wild pigs' global distribution. We offer guidance
      for efficient allocation of research effort and conservation resources across
      species and regions using a simple approach that can be applied to wild pigs and
      other alien invasive species globally.

PMID- 29593294
TI  - Characteristics of the fads2 gene promoter in marine teleost Epinephelus coioides
      and role of Sp1-binding site in determining promoter activity.
AB  - Delta6 fatty acyl desaturase (Fads2) is a rate-limiting enzyme in long-chain
      polyunsaturated fatty acids (LC-PUFA) biosynthesis. Comparative analysis of gene
      promoters of Fads2 between salmonids and carnivorous marine fish suggested that
      the lack of binding site for stimulatory protein 1 (Sp1) was responsible for the
      low expression of fads2 gene of carnivorous marine species. To confirm this
      speculation, the fads2 candidate promoter (2646 bp) was cloned from carnivorous
      marine teleost Epinephelus coioides, and 330 bp core regulatory region was
      identified. Several binding sites for transcriptional factors such as nuclear
      factor 1, nuclear factor Y, sterol regulatory element and hepatocyte nuclear
      factor 4gamma were identified, while that for Sp1 was shown to be absent in the
      promoter by both bioinformatic analysis and site-directed mutation. Moreover,
      after the Sp1-binding site from the fads2 promoter of herbivorous Siganus
      canaliculatus, the first marine teleost demonstrated to have LC-PUFA biosynthetic
      ability, was inserted into the corresponding region of E. coioides fads2
      promoter, activity was significantly increased. The results provided direct data
      for the importance of the Sp1-binding site in determining fads2 promoter
      activity, and indicated that its lack may be a reason for low expression of fads2
      and poor LC-PUFA biosynthetic ability in E. coioides.

PMID- 29593293
TI  - Beclin1 restricts RNA virus infection in plants through suppression and
      degradation of the viral polymerase.
AB  - Autophagy emerges as an essential immunity defense against intracellular
      pathogens. Here we report that turnip mosaic virus (TuMV) infection activates
      autophagy in plants and that Beclin1 (ATG6), a core component of autophagy,
      inhibits virus replication. Beclin1 interacts with NIb, the RNA-dependent RNA
      polymerase (RdRp) of TuMV, via the highly conserved GDD motif and the interaction
      complex is targeted for autophagic degradation likely through the adaptor protein
      ATG8a. Beclin1-mediated NIb degradation is inhibited by autophagy inhibitors.
      Deficiency of Beclin1 or ATG8a enhances NIb accumulation and promotes viral
      infection and vice versa. These data suggest that Beclin1 may be a selective
      autophagy receptor. Overexpression of a Beclin1 truncation mutant that binds to
      NIb but lacks the ability to mediate NIb degradation also inhibits virus
      replication. The Beclin1-RdRp interaction further extends to several RNA viruses.
      Thus Beclin1 restricts viral infection through suppression and also likely
      autophagic degradation of the viral RdRp.

PMID- 29593295
TI  - Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell
      survival in the hippocampal neurogenic niche.
AB  - Adult hippocampal neurogenesis is highly responsive to exercise, which promotes
      the proliferation of neural progenitor cells and the integration of newborn
      granule neurons in the dentate gyrus. Here we show that genetic ablation of the
      small GTPase, Dexras1, suppresses exercise-induced proliferation of neural
      progenitors, alters survival of mitotic and post-mitotic cells in a stage
      specific manner, and increases the number of mature newborn granule neurons.
      Dexras1 is required for exercise-triggered recruitment of quiescent neural
      progenitors into the cell cycle. Pharmacological inhibition of NMDA receptors
      enhances SGZ cell proliferation in wild-type but not dexras1-deficient mice,
      suggesting that NMDA receptor-mediated signaling is dependent on Dexras1. At the
      molecular level, the absence of Dexras1 abolishes exercise-dependent activation
      of ERK/MAPK and CREB, and inhibits the upregulation of NMDA receptor subunit
      NR2A, bdnf, trkB and vegf-a expression in the dentate gyrus. Our study reveals
      Dexras1 as an important stage-specific regulator of exercise-induced neurogenesis
      in the adult hippocampus by enhancing pro-mitogenic signaling to neural
      progenitor cells and modulating cell survival.

PMID- 29593296
TI  - Automated brightfield morphometry of 3D organoid populations by OrganoSeg.
AB  - Spheroid and organoid cultures are powerful in vitro models for biology, but size
      and shape diversity within the culture is largely ignored. To streamline
      morphometric profiling, we developed OrganoSeg, an open-source software that
      integrates segmentation, filtering, and analysis for archived brightfield images
      of 3D culture. OrganoSeg is more accurate and flexible than existing platforms,
      and we illustrate its potential by stratifying 5167 breast-cancer spheroid and
      5743 colon and colorectal-cancer organoid morphologies. Organoid transcripts
      grouped by morphometric signature heterogeneity were enriched for biological
      processes not prominent in the original RNA sequencing data. OrganoSeg enables
      complete, objective quantification of brightfield phenotypes, which may give
      insight into the molecular and multicellular mechanisms of organoid regulation.

PMID- 29593297
TI  - Over-elongation of centrioles in cancer promotes centriole amplification and
      chromosome missegregation.
AB  - Centrosomes are the major microtubule organising centres of animal cells.
      Deregulation in their number occurs in cancer and was shown to trigger
      tumorigenesis in mice. However, the incidence, consequence and origins of this
      abnormality are poorly understood. Here, we screened the NCI-60 panel of human
      cancer cell lines to systematically analyse centriole number and structure. Our
      screen shows that centriole amplification is widespread in cancer cell lines and
      highly prevalent in aggressive breast carcinomas. Moreover, we identify another
      recurrent feature of cancer cells: centriole size deregulation. Further
      experiments demonstrate that severe centriole over-elongation can promote
      amplification through both centriole fragmentation and ectopic procentriole
      formation. Furthermore, we show that overly long centrioles form over-active
      centrosomes that nucleate more microtubules, a known cause of invasiveness, and
      perturb chromosome segregation. Our screen establishes centriole amplification
      and size deregulation as recurrent features of cancer cells and identifies novel
      causes and consequences of those abnormalities.

PMID- 29593298
TI  - Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating
      photoreceptor.
AB  - Most opsins are G protein-coupled receptors that utilize retinal both as a ligand
      and as a chromophore. Opsins' main established mechanism is light-triggered
      activation through retinal 11-cis-to-all-trans photoisomerization. Here we report
      a vertebrate non-visual opsin that functions as a Gi-coupled retinal receptor
      that is deactivated by light and can thermally self-regenerate. This opsin,
      Opn5L1, binds exclusively to all-trans-retinal. More interestingly, the light
      induced deactivation through retinal trans-to-cis isomerization is followed by
      formation of a covalent adduct between retinal and a nearby cysteine, which
      breaks the retinal-conjugated double bond system, probably at the C11 position,
      resulting in thermal re-isomerization to all-trans-retinal. Thus, Opn5L1 acts as
      a reverse photoreceptor. We conclude that, like vertebrate rhodopsin, Opn5L1 is a
      unidirectional optical switch optimized from an ancestral bidirectional optical
      switch, such as invertebrate rhodopsin, to increase the S/N ratio of the signal
      transduction, although the direction of optimization is opposite to that of
      vertebrate rhodopsin.

PMID- 29593299
TI  - Bacterial diversity and community structure in the rhizosphere of four Ferula
      species.
AB  - The medicinal value of the Ferula L. has been recognized for more than a thousand
      years. Wild stocks of Ferula have declined dramatically because high economic
      value has led to overharvesting. The objective of this study was to compare the
      rhizosphere microbial community of four Ferula species [F. syreitschikowii K.
      Pol., F. gracilis (Ledeb.) Ledeb., F. ferulaeoides (Steud.) Korov., and F.
      lehmannii Boiss.] in the northern part of Xinjiang, China. The 16S rRNA sequences
      of rhizosphere bacteria were obtained with an Illumina paired-end sequence
      platform. Analysis was conducted to determine the richness and diversity of the
      rhizosphere bacterial communities. Two-way ANOVA indicated that plant species and
      soil depth had no significant effect on the alpha diversity of rhizobacteria.
      Linear discriminant analysis effect size showed that F. lehmannii followed by F.
      ferulaeoides had the most biomarkers and the highest taxon level, F.
      syreitschikowii and F. gracilis the least, while F. syreitschikowii and F.
      gracilis had the least property. This trend is consistent with reports that the
      medicinal value of F. lehmannii and F. ferulaeoides is greater than that of F.
      gracilis and F. syreitschikowii. The results of this study provide information
      that could be used for the commercial cultivation of Ferula spp.

PMID- 29593301
TI  - InAs/AlGaAs quantum dots for single-photon emission in a red spectral range.
AB  - We report on comparative optical studies of InAs/Al0.44Ga0.56As quantum dots
      (QDs) grown by molecular beam epitaxy either with or without a thin GaAs
      interlayer inserted between the AlGaAs barrier and InAs QDs. Emission properties
      of individual QDs are investigated by micro-photoluminescence spectroscopy using
      500-nm-size etched cylindric mesa structures. The single-photon statistics of the
      QDs of both types, emitting in the red spectral range between 636 and 750 nm, is
      confirmed by the measurements of the second-order correlation function. A
      negligibly small exciton fine structure splitting is detected in the majority of
      the QDs grown with the GaAs interlayer that implies the possibility of generating
      pairs of entangled photons with high entanglement fidelity.

PMID- 29593300
TI  - Surviving threats: neural circuit and computational implications of a new
      taxonomy of defensive behaviour.
AB  - Research on defensive behaviour in mammals has in recent years focused on
      elicited reactions; however, organisms also make active choices when responding
      to danger. We propose a hierarchical taxonomy of defensive behaviour on the basis
      of known psychological processes. Included are three categories of reactions
      (reflexes, fixed reactions and habits) and three categories of goal-directed
      actions (direct action-outcome behaviours and actions based on implicit or
      explicit forecasting of outcomes). We then use this taxonomy to guide a summary
      of findings regarding the underlying neural circuits.

PMID- 29593302
TI  - Unexpected Crossover in the kinetics of mutarotation in the supercooled region:
      the role of H-bonds.
AB  - Intra- and intermolecular studies on the molten L-sorbose have been carried out
      at variable temperature conditions to determine the crosover temperature (T c ).
      In addition, isothermal time-dependent FTIR and Raman measurements were performed
      to probe the pace of mutarotation and activation energy of this reaction in the
      studied saccharide, which varied from 53-62 kJ/mol up to 177-192 kJ/mol below and
      above T c , respectively. To explain the change in activation barrier for the
      mutarotation a complementary analysis using difference FTIR spectra collected
      around T c  = 365 K in the hydroxyl region has been done. It was found that the
      alteration of kinetic parameters and molecular dynamics around T c are strictly
      related to the variation in the strength of H-bonds which above T c are
      significantly weaken, increasing the freedom of rotation of functional groups and
      movement of individual molecules. That phenomenon most likely affects the proton
      transfer, underlying molecular mechanism of mutarotation, which may lead to the
      significant increase in activation barrier. The new insight into a molecular
      aspect of the mutarotation around T c has created an opportunity to better
      understanding the relationship between physics of condensed matter and the
      potential role of H-bonds dynamics on the progress of the chemical reaction in
      highly viscous systems.

PMID- 29593303
TI  - Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention
      Sites.
AB  - A variety of environmental toxicants and factors have been shown to induce the
      epigenetic transgenerational inheritance of disease and phenotypic variation.
      Epigenetic alterations in the germline (sperm or egg) are required to transmit
      transgenerational phenotypes. The current study was designed to investigate the
      potential role of histones in sperm to help mediate the epigenetic
      transgenerational inheritance. The agricultural fungicide vinclozolin and the
      pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to
      promote the epigenetic transgenerational inheritance of disease. Purified cauda
      epididymal sperm were collected from the transgenerational F3 generation control
      and exposure lineage male rats for histone analysis. A reproducible core of
      histone H3 retention sites was observed using an H3 chromatin immunoprecipitation
      (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group
      of H3 retention sites plus additional differential histone retention sites (DHRs)
      were observed in the F3 generation exposure lineage sperm. Although new histone
      H3 retention sites were observed, negligible change in histone modification
      (methylation of H3K27me3) was observed between the control and exposure lineages.
      Observations demonstrate that in addition to alterations in sperm DNA methylation
      and ncRNA previously identified, the induction of differential histone retention
      sites (DHRs) also appear to be involved in environmentally induced epigenetic
      transgenerational inheritance.

PMID- 29593304
TI  - Quantum probe hyperpolarisation of molecular nuclear spins.
AB  - Hyperpolarisation of nuclear spins is important in overcoming sensitivity and
      resolution limitations of magnetic resonance imaging and nuclear magnetic
      resonance spectroscopy. Current hyperpolarisation techniques require high
      magnetic fields, low temperatures, or catalysts. Alternatively, the emergence of
      room temperature spin qubits has opened new pathways to achieve direct nuclear
      spin hyperpolarisation. Employing a microwave-free cross-relaxation induced
      polarisation protocol applied to a nitrogen vacancy qubit, we demonstrate quantum
      probe hyperpolarisation of external molecular nuclear spins to ~50% under ambient
      conditions, showing a single qubit increasing the polarisation of ~106 nuclear
      spins by six orders of magnitude over the thermal background. Results are
      verified against a detailed theoretical treatment, which also describes how the
      system can be scaled up to a universal quantum hyperpolarisation platform for
      macroscopic samples. Our results demonstrate the prospects for this approach to
      nuclear spin hyperpolarisation for molecular imaging and spectroscopy and its
      potential to extend beyond into other scientific areas.

PMID- 29593305
TI  - Pigmentation pattern and developmental constraints: flight muscle attachment
      sites delimit the thoracic trident of Drosophila melanogaster.
AB  - In their seminal paper published in 1979, Gould and Lewontin argued that some
      traits arise as by-products of the development of other structures and not for
      direct utility in themselves. We show here that this applies to the trident, a
      pigmentation pattern observed on the thorax of Drosophila melanogaster. Using
      reporter constructs, we show that the expression domain of several genes encoding
      pigmentation enzymes follows the trident shape. This domain is complementary to
      the expression pattern of stripe (sr), which encodes an essential transcription
      factor specifying flight muscle attachment sites. We demonstrate that sr limits
      the expression of these pigmentation enzyme genes to the trident by repressing
      them in its own expression domain, i.e. at the flight muscle attachment sites. We
      give evidence that repression of not only yellow but also other pigmentation
      genes, notably tan, is involved in the trident shape. The flight muscle
      attachment sites and sr expression patterns are remarkably conserved in dipterans
      reflecting the essential role of sr. Our data suggest that the trident is a by
      product of flight muscle attachment site patterning that arose when sr was co
      opted for the regulation of pigmentation enzyme coding genes.

PMID- 29593306
TI  - Effect of live yeast Saccharomyces cerevisiae (Actisaf Sc 47) supplementation on
      the performance and hindgut microbiota composition of weanling pigs.
AB  - As an alternative to antibiotic growth promoters, live yeast supplementation has
      proven useful in reducing weaning stress and improving performance parameters of
      piglets. Here, we compared the performance and hindgut microbiota of weanling
      piglets subjected to different pre- and post-weaning yeast supplementation
      regimens using a live strain of Saccharomyces cerevisiae (Actisaf Sc 47). Average
      feed intake and average daily weight gain of piglets within Yeast-Control and
      Yeast-Yeast groups were higher than those in the Control-Control group. Yeast
      supplementation resulted in development of microbial communities that were
      phylogenetically more homogenous and less dispersed compared to the microbiota of
      control piglets. Key bacterial taxa overrepresented in the microbiota of yeast
      supplemented piglets included phylum Actinobacteria, specifically family
      Coriobacteriaceae, as well as Firmicutes families Ruminococcaceae,
      Clostridiaceae, Peptostreptococcaceae, and Peptococcaceae. Correlation network
      analysis revealed that yeast supplementation was associated with enrichment of
      positive correlations among proportions of different bacterial genera within the
      hindgut ecosystem. In particular, within the cecal microbiota of supplemented
      piglets, higher numbers of positive correlations were observed among potentially
      beneficial genera of the phyla Actinobacteria and Firmicutes, suggesting a
      mechanism by which yeast supplementation may contribute to regulation of
      intestinal homeostasis and improved performance of piglets.

PMID- 29593308
TI  - The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by
      Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.
AB  - Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent
      years. Although more targeted than conventional chemotherapy, TKIs exhibit
      substantial cardiotoxicity, often manifesting as hypertension or heart failure.
      Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and
      investigated underlying alterations of myocyte calcium homeostasis. We found that
      sorafenib reversibly decreased developed force in auxotonically contracting human
      myocardia (3 uM: -25 +/- 4%, 10 uM: -29 +/- 7%, 30 uM: -43 +/- 12%, p < 0.01),
      reduced peak cytosolic calcium concentrations in isolated cardiomyocytes (10 uM:
      52 +/- 8.1% of baseline, p < 0.001), and slowed cytosolic calcium removal
      kinetics (RT50, RT10, Tau, p < 0.05). Beta-adrenergic stimulation induced
      augmentation of calcium transient (CaT) amplitude was attenuated in sorafenib
      treated cells (2.7 +/- 0.3-fold vs. 3.6 +/- 0.2-fold in controls, p < 0.001).
      Sarcoplasmic reticulum (SR) calcium content was reduced to 67 +/- 4% (p < 0.01),
      and SR calcium re-uptake slowed (p < 0.05). Sorafenib significantly reduced
      serine 16 phosphorylation of phospholamban (PLN, p < 0.05), while PLN threonine
      17 and CaMKII (T286) phosphorylation were not altered. Our data demonstrate that
      sorafenib acutely impairs cardiac contractility by reducing S16 PLN
      phosphorylation, leading to reduced SR calcium content, CaT amplitude, and slowed
      cytosolic calcium removal. These results indicate myocyte intrinsic
      cardiotoxicity irrespective of effects on the vasculature and chronic cardiac
      remodeling.

PMID- 29593307
TI  - Morphology of Immunomodulation in Breast Cancer Tumor Draining Lymph Nodes
      Depends on Stage and Intrinsic Subtype.
AB  - Cancer research of immune-modulating mechanisms mainly addresses the role of
      tumor-infiltrating immune cells. Mechanisms modulating the adaptive immune system
      at the primary activation site - the draining lymph node (LN) - are less
      investigated. Here we present tumor-caused histomorphological changes in tumor
      draining LNs of breast cancer patients, dependent on the localization (sentinel
      LN vs. non-sentinel LN), the tumor size, the intrinsic subtype and nodal
      metastatic status. The quantitative morphological study was conducted in breast
      cancer patients with at least one sentinel LN and no neoadjuvant therapy. All LNs
      were annotated considering to their topographical location, stained for IgD/H&E,
      digitized and quantitatively analyzed. In 206 patients, 394 sentinels and 940 non
      sentinel LNs were categorized, comprising 40758 follicles and 7074 germinal
      centers. Subtype specific immunomorphological patterns were detectable:
      Follicular density was higher in LNs of Her2 enriched hormone receptor positive
      and triple-negative breast cancers whereas hormone receptor positive breast
      cancers showed more macrophage infiltrations in the LN cortex. Follicles are
      rounder in metastatic LNs and non-sentinel LNs. The identified
      immunomorphological changes reflect different underlying immunomodulations taking
      place in the tumor-draining LNs and should therefore be considered as possible
      prognostic and predictive markers for LN metastasis and therapy associated
      immunomodulation.

PMID- 29593309
TI  - Cold Atmospheric Plasma Induces ATP-Dependent Endocytosis of Nanoparticles and
      Synergistic U373MG Cancer Cell Death.
AB  - Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic
      vehicles. However, selective targeting and uptake in cancer cells remains
      challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve
      synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we
      demonstrate both rate of AuNP uptake and total amount accumulated in U373MG
      Glioblastoma multiforme (GBM) cells are significantly increased when exposed to
      75 kV CAP generated by dielectric barrier discharge. No significant changes in
      the physical parameters of AuNP were caused by CAP but active transport
      mechanisms were stimulated in cells. Unlike many other biological effects of CAP,
      long-lived reactive species were not involved, and plasma-activated liquids did
      not replicate the effect. Chemical effects induced by direct and indirect
      exposure to CAP appears the dominant mediator of enhanced uptake. Transient
      physical alterations of membrane integrity played a minor role. 3D-reconstruction
      of deconvoluted confocal images confirmed AuNP accumulation in lysosomes and
      other acidic vesicles, which will be useful for future drug delivery and
      diagnostic strategies. Toxicity of AuNP significantly increased by 25-fold when
      combined with CAP. Our data indicate that direct exposure to CAP activates AuNP
      dependent cytotoxicity by increasing AuNP endocytosis and trafficking to
      lysosomes in U373MG cells.

PMID- 29593310
TI  - First insights of peptidoglycan amidation in Gram-positive bacteria - the high
      resolution crystal structure of Staphylococcus aureus glutamine amidotransferase
      GatD.
AB  - Gram-positive bacteria homeostasis and antibiotic resistance mechanisms are
      dependent on the intricate architecture of the cell wall, where amidated
      peptidoglycan plays an important role. The amidation reaction is carried out by
      the bi-enzymatic complex MurT-GatD, for which biochemical and structural
      information is very scarce. In this work, we report the first crystal structure
      of the glutamine amidotransferase member of this complex, GatD from
      Staphylococcus aureus, at 1.85 A resolution. A glutamine molecule is found close
      to the active site funnel, hydrogen-bonded to the conserved R128. In vitro
      functional studies using 1H-NMR spectroscopy showed that S. aureus MurT-GatD
      complex has glutaminase activity even in the absence of lipid II, the MurT
      substrate. In addition, we produced R128A, C94A and H189A mutants, which were
      totally inactive for glutamine deamidation, revealing their essential role in
      substrate sequestration and catalytic reaction. GatD from S. aureus and other
      pathogenic bacteria share high identity to enzymes involved in cobalamin
      biosynthesis, which can be grouped in a new sub-family of glutamine
      amidotransferases. Given the ubiquitous presence of GatD, these results provide
      significant insights into the molecular basis of the so far undisclosed amidation
      mechanism, contributing to the development of alternative therapeutics to fight
      infections.

PMID- 29593311
TI  - Mutations in the CDS and promoter of BjuA07.CLV1 cause a multilocular trait in
      Brassica juncea.
AB  - Multilocular trait has recently attracted considerable attention for its
      potential to increase yield. Our previous studies indicated that two genes (Bjln1
      and Bjln2) are responsible for multilocular siliques in Brassica juncea and the
      Bjln1 gene has been delimited to a 208-kb region. In present study, the Bjln1
      gene was successfully isolated using the map-based cloning method.
      Complementation test indicated that the BjuA07.CLV1 (equivalent to BjLn1) could
      rescue the multilocular phenotype and generate bilocular siliques. Two amino
      acids changes at positions 28 and 63 in BjuA07.clv1 as well as a 702-bp deletion
      in its promoter have been proved to affect the carpel numbers. Microscopic
      analyses suggested that BjuA07.CLV1 is involved in the maintenance of shoot and
      floral meristem size. The expression level of BjuA07.clv1 was significantly
      reduced in the SAM. Furthermore, WUS, CLV2, CLV3, RPK2 and POL, key genes in the
      CLV/WUS signal pathway, showed lower expression level in the multilocular plants.
      These data suggest that the mutations in the CDS and promoter of BjuA07.clv1
      reduced its function and expression level, which disturbed CLV/WUS signal
      pathway, thereby leading to the enlargement of the shoot and floral meristem and
      resulting in the multilocular siliques.

PMID- 29593312
TI  - The sudden death and sudden birth of quantum discord.
AB  - The interaction of quantum system and its environment brings out abundant quantum
      phenomenons. The sudden death of quantum resources, including entanglement,
      quantum discord and coherence, have been studied from the perspective of quantum
      breaking channels (QBC). QBC of quantum resources reveal the common features of
      quantum resources. The definition of QBC implies the relationship between quantum
      resources. However, sudden death of quantum resources can also appear under some
      other quantum channels. We consider the dynamics of Bell-diagonal states under a
      stochastic dephasing noise along the z-direction, and the sudden death and sudden
      birth of quantum discord are investigated. Next we explain this phenomenon from
      the geometric structure of quantum discord. According to the above results, the
      states with sudden death and sudden birth can be filtered in three-parameter
      space. Then we provide two necessary conditions to judge which kind of noise
      channels can make Bell-diagonal states sudden death and sudden birth. Moreover,
      the relation between quantum discord and coherence indicates that the sudden
      death and sudden birth of quantum discord implies the sudden death and sudden
      birth of coherence in an optimal basis.

PMID- 29593313
TI  - Reduced Translocation of Glyphosate and Dicamba in Combination Contributes to
      Poor Control of Kochia scoparia: Evidence of Herbicide Antagonism.
AB  - Kochia scoparia is a troublesome weed across the Great Plains of North America.
      Glyphosate and dicamba have been used for decades to control K. scoparia. Due to
      extensive selection, glyphosate- and dicamba-resistant (GDR) K. scoparia have
      evolved in the USA. Herbicide mixtures are routinely used to improve weed
      control. Herbicide interactions if result in an antagonistic effect can
      significantly affect the management of weeds, such as K. scoparia. To uncover the
      interaction of glyphosate and dicamba when applied in combination in K. scoparia
      management the efficacies of different doses of glyphosate plus dicamba were
      evaluated under greenhouse and field conditions using GDR and a known glyphosate-
      and dicamba-susceptible (GDS) K. scoparia. The results of greenhouse and field
      studies suggest that the combination of glyphosate and dicamba application
      controlled GDS, but glyphosate alone provided a better control of GDR K. scoparia
      compared to glyphosate plus dicamba combinations. Furthermore, investigation of
      the basis of this response suggested glyphosate and dicamba interact
      antagonistically and consequently, the translocation of both herbicides was
      significantly reduced resulting in poor control of K. scoparia. Therefore, a
      combination of glyphosate plus dicamba may not be a viable option to control GDR
      K. scoparia.

PMID- 29593315
TI  - A Lethal Fungus Infects the Chinese White Wax Scale Insect and Causes Dramatic
      Changes in the Host Microbiota.
AB  - The Chinese white wax scale insect (Ericerus pela) is an economically valuable
      species with an important role in wax production. Recently, in a greenhouse in
      Kunming, we identified a genus of fungus that infects and kills E. pela females.
      This study sought to perform the molecular detection of entomopathogens and
      analyze the changes in the host microbiota after entomopathogen infection. We
      used library construction, high-throughput sequencing and real-time quantitative
      polymerase chain reaction (RT-qPCR) to identify the fungi infecting adult E.
      pela, to understand the changes in the host organism, and to determine the
      distribution of the entomopathogens. Cladosporium langeronii and C.
      sphaerospermum were the main pathogenic species that infected the E. pela
      females, and they were most prevalent in the dorsal cuticle. In vivo, after
      infection, the proportion of Cladosporium clearly increased. The infection had
      little influence on the fungal community but had a strong influence on the
      bacterial community. After infection, Arsenophonus was dominant, and numerous
      bacterial genera disappeared. However, Rickettsia, instead of Arsenophonus,
      became dominant in the Cladosporium-infected individuals that had also been
      infected with Rickettsia. We identified the species that infected E. pela females
      and determined the influence of infection on the host microorganisms.

PMID- 29593314
TI  - Oncofetal gene SALL4 reactivation by hepatitis B virus counteracts miR-200c in PD
      L1-induced T cell exhaustion.
AB  - A chronic viral or tumor microenvironment can push T cells to exhaustion by
      promoting coinhibitory ligand expression. However, how host factors control
      coinhibitory ligand expression and whether viral infection breaks this control
      during tumor progress is unknown. Here we show a close negative correlation
      between SALL4 or PD-L1 and miR-200c in tumors from 98 patients with HBV-related
      hepatocellular carcinoma. SALL4 or PD-L1 expression correlates negatively with
      miR-200c expression, and patients with lower levels of SALL4 or PD-L1 and higher
      miR-200c survive longer. Moreover, over-expression of miR-200c antagonizes HBV
      mediated PD-L1 expression by targeting 3'-UTR of CD274 (encoding PD-L1) directly,
      and reverses antiviral CD8+ T cell exhaustion. MiR-200c transcription is
      inhibited by oncofetal protein SALL4, which is re-expressed through HBV-induced
      STAT3 activation in adulthood. We propose that an HBV-pSTAT3-SALL4-miR-200c axis
      regulates PD-L1. Therapeutic strategies to influence this axis might reverse
      virus-induced immune exhaustion.

PMID- 29593316
TI  - U-turns in the brain.

PMID- 29593318
TI  - Microglia's heretical self-renewal.

PMID- 29593319
TI  - Author Correction: The experience of spasticity after spinal cord injury:
      perceived characteristics and impact on daily life.
AB  - There is an author correction associated with this article.

PMID- 29593320
TI  - Paraspeckle factor turns TGF-beta1 pro-metastatic.

PMID- 29593321
TI  - A lncRNA GUARDINg genome integrity.

PMID- 29593317
TI  - CA1 pyramidal cell diversity enabling parallel information processing in the
      hippocampus.
AB  - Hippocampal network operations supporting spatial navigation and declarative
      memory are traditionally interpreted in a framework where each hippocampal area,
      such as the dentate gyrus, CA3, and CA1, consists of homogeneous populations of
      functionally equivalent principal neurons. However, heterogeneity within
      hippocampal principal cell populations, in particular within pyramidal cells at
      the main CA1 output node, is increasingly recognized and includes developmental,
      molecular, anatomical, and functional differences. Here we review recent progress
      in the delineation of hippocampal principal cell subpopulations by focusing on
      radially defined subpopulations of CA1 pyramidal cells, and we consider how
      functional segregation of information streams, in parallel channels with
      nonuniform properties, could represent a general organizational principle of the
      hippocampus supporting diverse behaviors.

PMID- 29593322
TI  - CK1alpha promotes tumour suppressive autophagy.

PMID- 29593323
TI  - Setting up the dermis for scar-free healing.

PMID- 29593324
TI  - A PhD state of mind.

PMID- 29593325
TI  - Gunter Blobel (1936-2018).

PMID- 29593326
TI  - PSPC1 mediates TGF-beta1 autocrine signalling and Smad2/3 target switching to
      promote EMT, stemness and metastasis.
AB  - Activation of metastatic reprogramming is critical for tumour metastasis.
      However, more detailed knowledge of the underlying mechanism is needed to enable
      targeted intervention. Here, we show that paraspeckle component 1 (PSPC1),
      identified in an aberrant 13q12.11 locus, is upregulated and associated with poor
      survival in patients with cancer. PSPC1 promotes tumorigenesis, epithelial-to
      mesenchymal transition (EMT), stemness and metastasis in multiple cell types and
      in spontaneous mouse cancer models. PSPC1 is the master activator for
      transcription factors of EMT and stemness and accompanies c-Myc activation to
      facilitate tumour growth. PSPC1 increases transforming growth factor-beta1 (TGF
      beta1) secretion through an interaction with phosphorylated and nuclear Smad2/3
      to potentiate TGF-beta1 autocrine signalling. Moreover, PSPC1 acts as a
      contextual determinant of the TGF-beta1 pro-metastatic switch to alter Smad2/3
      binding preference from tumour-suppressor to pro-metastatic genes. Having
      validated the PSPC1-Smads-TGF-beta1 axis in various cancers, we conclude that
      PSPC1 is a master activator of pro-metastatic switches and a potential target for
      anti-metastasis drugs.

PMID- 29593327
TI  - Two succeeding fibroblastic lineages drive dermal development and the transition
      from regeneration to scarring.
AB  - During fetal development, mammalian back-skin undergoes a natural transition in
      response to injury, from scarless regeneration to skin scarring. Here, we
      characterize dermal morphogenesis and follow two distinct embryonic fibroblast
      lineages, based on their history of expression of the engrailed 1 gene. We use
      single-cell fate-mapping, live three dimensional confocal imaging and in silico
      analysis coupled with immunolabelling to reveal unanticipated structural and
      regional complexity and dynamics within the dermis. We show that dermal
      development and regeneration are driven by engrailed 1-history-naive fibroblasts,
      whose numbers subsequently decline. Conversely, engrailed 1-history-positive
      fibroblasts possess scarring abilities at this early stage and their expansion
      later on drives scar emergence. The transition can be reversed, locally, by
      transplanting engrailed 1-naive cells. Thus, fibroblastic lineage replacement
      couples the decline of regeneration with the emergence of scarring and creates
      potential clinical avenues to reduce scarring.

PMID- 29593328
TI  - Deconstructing the pluripotency gene regulatory network.
AB  - Pluripotent stem cells can be isolated from embryos or derived by reprogramming.
      Pluripotency is stabilized by an interconnected network of pluripotency genes
      that cooperatively regulate gene expression. Here we describe the molecular
      principles of pluripotency gene function and highlight post-transcriptional
      controls, particularly those induced by RNA-binding proteins and alternative
      splicing, as an important regulatory layer of pluripotency. We also discuss
      heterogeneity in pluripotency regulation, alternative pluripotency states and
      future directions of pluripotent stem cell research.

PMID- 29593329
TI  - TP53INP2 regulates adiposity by activating beta-catenin through autophagy
      dependent sequestration of GSK3beta.
AB  - Excessive fat accumulation is a major risk factor for the development of type 2
      diabetes mellitus and other common conditions, including cardiovascular disease
      and certain types of cancer. Here, we identify a mechanism that regulates
      adiposity based on the activator of autophagy TP53INP2. We report that TP53INP2
      is a negative regulator of adipogenesis in human and mouse preadipocytes. In
      keeping with this, TP53INP2 ablation in mice caused enhanced adiposity, which was
      characterized by greater cellularity of subcutaneous adipose tissue and increased
      expression of master adipogenic genes. TP53INP2 modulates adipogenesis through
      autophagy-dependent sequestration of GSK3beta into late endosomes. GSK3beta
      sequestration was also dependent on ESCRT activity. As a result, TP53INP2
      promotes greater beta-catenin levels and induces the transcriptional activity of
      TCF/LEF transcription factors. These results demonstrate a link between
      autophagy, sequestration of GSK3beta into late endosomes and inhibition of
      adipogenesis in vivo.

PMID- 29593330
TI  - CK1alpha suppresses lung tumour growth by stabilizing PTEN and inducing
      autophagy.
AB  - The contribution of autophagy to cancer development remains controversial,
      largely owing to the fact that autophagy can be tumour suppressive or oncogenic
      in different biological contexts. Here, we show that in non-small-cell lung
      cancer (NSCLC), casein kinase 1 alpha 1 (CK1alpha) suppresses tumour growth by
      functioning as an autophagy inducer to activate an autophagy-regulating, tumour
      suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1alpha bound the C
      terminal tail of PTEN and enhanced both PTEN stability and activity by
      competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating
      PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a
      induced transcription of Atg7. Notably, blocking CK1alpha-induced Atg7-dependent
      autophagy cooperates with oncogenic HRasV12 to initiate tumorigenesis of lung
      epithelial cells. An association of a CK1alpha-modulated autophagic program with
      the anti-neoplastic activities of the CK1alpha/PTEN/FOXO3a/Atg7 axis was
      demonstrated in xenografted tumour models and human NSCLC specimens. This
      provides insights into the biological and potentially clinical significance of
      autophagy in NSCLC.

PMID- 29593331
TI  - GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic
      stability.
AB  - The list of long non-coding RNAs (lncRNAs) involved in the p53 pathway of the DNA
      damage response is rapidly expanding, but whether lncRNAs have a role in
      maintaining the de novo structure of DNA is unknown. Here, we demonstrate that
      the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity
      under steady-state conditions and after exposure to exogenous genotoxic stress.
      GUARDIN is necessary for preventing chromosome end-to-end fusion through
      maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by
      sequestering microRNA-23a. Moreover, GUARDIN also sustains breast cancer 1
      (BRCA1) stability by acting as an RNA scaffold to facilitate the
      heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1).
      As such, GUARDIN silencing triggered apoptosis and senescence, enhanced
      cytotoxicity of additional genotoxic stress and inhibited cancer xenograft
      growth. Thus, GUARDIN may constitute a target for cancer treatment.

PMID- 29593332
TI  - The importance of a potential phosphorylation site in enamelin on enamel
      formation.
AB  - Enamelin (ENAM) has three putative phosphoserines (pSers) phosphorylated by a
      Golgi-associated secretory pathway kinase (FAM20C) based on their distinctive Ser
      x-Glu (S-x-E) motifs. Fam20C-knockout mice show severe enamel defects similar to
      those in the Enam-knockout mice, implying an important role of the pSers in ENAM.
      To determine the role of pSer55 in ENAM, we characterized ENAMRgsc514 mice, in
      which Ser55 cannot be phosphorylated by FAM20C due to an E57>G57 mutation in the
      S-x-E motif. The enamel microstructure of 4-week-old mice was examined by
      scanning electron microscopy. The teeth of 6-day-old mice were characterized by
      histology and immunohistochemistry. The protein lysates of the first lower molars
      of 4-day-old mice were analyzed by Western immunoblotting using antibodies
      against ENAM, ameloblastin and amelogenin. ENAMRgsc514 heterozygotes showed a
      disorganized enamel microstructure, while the homozygotes had no enamel on the
      dentin surface. The N-terminal fragments of ENAM in the heterozygotes were
      detained in the ameloblasts and localized in the mineralization front of enamel
      matrix, while those in the WT mice were secreted out of ameloblasts and
      distributed evenly in the outer 1/2 of enamel matrix. Surprisingly, the ~15  kDa
      C-terminal fragments of ameloblastin were not detected in the molar lysates of
      the homozygotes. These results suggest that the phosphorylation of Ser55 may be
      an essential posttranslational modification of ENAM and is required for the
      interaction with other enamel matrix molecules such as ameloblastin in mediating
      the structural organization of enamel matrix and protein-mineral interactions
      during enamel formation.International Journal of Oral Science (2017) 9;e4;
      doi:10.1038/ijos.2017.41; published online 29 November 2017.

PMID- 29593333
TI  - Schottky model for triboelectric temperature dependence.
AB  - The triboelectric effect, charging by contact, is the working principle in a
      device called a triboelectric nanogenerator. They are used as efficient energy
      transducers in energy harvesting. In such generators the charging of surfaces at
      contact is followed by a separation of the surfaces increasing the electrical
      energy which can subsequently be used. Different materials have different
      triboelectric potentials leading to charging at contact. The temperature
      dependence of the charging has just recently been studied: the triboelectric
      effect is decreasing with temperature for a generator of Al-PTFE-Cu. Here, we
      suggest a mechanism to explain this effect assuming ion transfer using a two
      level Schottky model where the two levels corresponds to the two surfaces. The
      difference in binding energy for ions on the two surfaces then enters the formula
      for charging. We fit the triboelectric power density as a function of temperature
      obtained from a two-level Schottky model to measured data for nanogenerators made
      of Al-PTFE-Cu found in three references. We obtain an average separation energy
      corresponding to a temperature of 365 K which is of the right magnitude for
      physically adsorbed atoms. We anticipate that this model could be used for many
      types of triboelectric nanogenerators.

PMID- 29593334
TI  - USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer
      cells.
AB  - Gain-of-function p53 mutants such as p53-R175H form stable aggregates that
      accumulate in cells and play important roles in cancer progression. Selective
      degradation of gain-of-function p53 mutants has emerged as a highly attractive
      therapeutic strategy to target cancer cells harboring specific p53 mutations. We
      identified a small molecule called MCB-613 to cause rapid ubiquitination, nuclear
      export, and degradation of p53-R175H through a lysosome-mediated pathway, leading
      to catastrophic cancer cell death. In contrast to its effect on the p53-R175H
      mutant, MCB-613 causes slight stabilization of p53-WT and has weaker effects on
      other p53 gain-of-function mutants. Using state-of-the-art genetic and chemical
      approaches, we identified the deubiquitinase USP15 as the mediator of MCB-613's
      effect on p53-R175H, and established USP15 as a selective upstream regulator of
      p53-R175H in ovarian cancer cells. These results confirm that distinct pathways
      regulate the turnover of p53-WT and the different p53 mutants and open new
      opportunities to selectively target them.

PMID- 29593335
TI  - Differences in cognitive functions between cytomegalovirus-infected and
      cytomegalovirus-free university students: a case control study.
AB  - Cytomegalovirus (CMV) is the herpetic virus, which infects 45-100% people
      worldwide. Many reports suggest that CMV could impair cognitive functions of
      infected subjects. Here we searched for indices of effects of CMV on infected
      subjects' intelligence and knowledge. The Intelligence Structure Test I-S-T 2000
      R was used to compare IQ of 148 CMV-infected and 135 CMV-free university
      students. Infected students expressed higher intelligence. Paradoxically, their
      IQ decreased with decreasing concentration of anti-CMV antibodies, which can be
      used, statistically, as a proxy of the time passed from the moment of infection
      in young subjects when the age of subjects is statistically controlled. The
      paradox of seemingly higher intelligence of CMV infected subjects could be
      explained by the presence of the subpopulation of about 5-10% CMV-positive
      individuals in the population of "CMV-negative students". These false negative
      subjects had probably not only the oldest infections and therefore the lowest
      concentration of anamnestic antibodies, but also the lowest intelligence among
      the infected students. Prevalence of CMV infection in all countries is very high,
      approaching sometimes 90%. Therefore, the total impact of CMV on human
      intelligence may be large.

PMID- 29593336
TI  - Germline mutations as potential causes of childhood solid tumours: comments on
      the Norwegian childhood cancer cohort study.
AB  - Some cancer predisposing germline mutations cause overt birth defects and
      congenital anomalies. Others are clinically silent and can only be suspected by
      the presence of increased cancer incidence in family members. A new study shows
      that long-term monitoring of families may be needed to discover previously
      unsuspected underlying cancer predisposing mutations.

PMID- 29593337
TI  - End-of-life decision-making across cancer types: results from a nationwide
      retrospective survey among treating physicians.
AB  - BACKGROUND: The treatment of advanced cancer often involves potentially life
      shortening end-of-life decisions (ELDs). This study aimed to examine the
      prevalence and characteristics of ELDs in different cancer types. METHODS: A
      nationwide death certificate study was conducted based on a large random sample
      of all deaths in Flanders, Belgium, between 1 January and 30 June 2013. All
      cancer deaths were selected (n = 2392). Attending physicians were sent a
      questionnaire about ELDs and the preceding decision-making process. RESULTS: The
      response rate was 58.3%. Across cancer types, a non-treatment decision occurred
      in 7.6-14.0%, intensified pain and symptom alleviation in 37.5-41.7%, euthanasia
      or physician-assisted suicide in 8.7-12.6%, and life shortening without explicit
      patient request in 1.0-2.4%. ELD prevalence did not differ significantly by
      cancer type. Reasons for ELDs were most frequently patient's physical suffering
      and lack of prospect of improvement. 'Anticipated further suffering' and
      'unbearable situation for relatives' were reasons more often reported in
      haematological cancer than in other cancer types. Patient, family, and caregiver
      involvement in decision-making did not differ across cancer types. CONCLUSIONS:
      Euthanasia or physician-assisted suicide rates were relatively high in all cancer
      types. Neither the prevalence of ELDs nor characteristics of the decision-making
      process differed substantially between cancer types. This indicates a uniform
      approach to end-of-life care, including palliative care, across oncological
      settings.

PMID- 29593338
TI  - The effect of selection and referral biases for the treatment of localised
      prostate cancer with surgery or radiation.
AB  - BACKGROUND: Consultation with radiation oncologists, in addition to urologists,
      is advocated for patients diagnosed with prostate cancer. Treatment patterns for
      patients receiving consultation from radiation oncologists in addition to
      urologists have not previously been described. METHODS: We conducted a matched
      cohort study of men with newly diagnosed non-metastatic prostate cancer in
      Ontario, Canada. Patients who underwent consultation with a radiation oncologist
      prior to treatment were matched 1:1 with patients managed by a urologist alone
      based on tumour and patient characteristics. We examined rates of active
      treatment (surgery or radiotherapy) within one year following diagnosis. RESULTS:
      Among 5708 matched pairs (11,416 patients), those who received radiation oncology
      consultation were more likely to undergo active treatments whether they had
      intermediate or high-risk disease (88.6% vs. 65.9%, p < 0.0001; adjusted odds
      ratio 4.0, 95% CI: 3.6-4.4) or low-risk disease (56.1% vs. 13.3%, p < 0.0001;
      adjusted odds ratio 8.4, 95% CI: 6.7-10.6). This effect persisted after
      considering age, comorbidity, tumour volume and year of diagnosis. CONCLUSIONS:
      Patients newly diagnosed with prostate cancer who receive radiation oncology
      consultation are associated with a higher rate of active treatment, compared to
      patients managed by urologists only. Selection and referral biases, and
      unmeasured confounding such as patient preference must be considered as important
      factors attributing this association.

PMID- 29593340
TI  - Anti-CTLA-4 immunotherapy: uncoupling toxicity and efficacy.

PMID- 29593339
TI  - Quantitative proteomic profiling of primary cancer-associated fibroblasts in
      oesophageal adenocarcinoma.
AB  - BACKGROUND: Cancer-associated fibroblasts (CAFs) form the major stromal component
      of the tumour microenvironment (TME). The present study aimed to examine the
      proteomic profiles of CAFs vs. normal fibroblasts (NOFs) from patients with
      oesophageal adenocarcinoma to gain insight into their pro-oncogenic phenotype.
      METHODS: CAFs/NOFs from four patients were sub-cultured and analysed using
      quantitative proteomics. Differentially expressed proteins (DEPs) were subjected
      to bioinformatics and compared with published proteomics and transcriptomics 
      datasets. RESULTS: Principal component analysis of all profiled proteins showed
      that CAFs had high heterogeneity and clustered separately from NOFs.
      Bioinformatics interrogation of the DEPs demonstrated inhibition of adhesion of
      epithelial cells, adhesion of connective tissue cells and cell death of
      fibroblast cell lines in CAFs vs. NOFs (p < 0.0001). KEGG pathway analysis showed
      a significant enrichment of the insulin-signalling pathway (p = 0.03). Gene
      ontology terms related with myofibroblast phenotype, metabolism, cell
      adhesion/migration, hypoxia/oxidative stress, angiogenesis, immune/inflammatory
      response were enriched in CAFs vs. NOFs. Nestin, a stem-cell marker up-regulated
      in CAFs vs. NOFs, was confirmed to be expressed in the TME with
      immunohistochemistry. CONCLUSIONS: The identified pathways and participating
      proteins may provide novel insight on the tumour-promoting properties of CAFs and
      unravel novel adjuvant therapeutic targets in the TME.

PMID- 29593341
TI  - MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated
      RIG-I degradation.
AB  - Trithorax group protein MLL5 is an important epigenetic modifier that controls
      cell cycle progression, chromatin architecture maintenance, and hematopoiesis.
      However, whether MLL5 has a role in innate antiviral immunity is largely unknown.
      Here we show that MLL5 suppresses the RIG-I-mediated anti-viral immune response.
      Mll5-deficient mice infected with vesicular stomatitis virus show enhanced anti
      viral innate immunity, reduced morbidity, and viral load. Mechanistically, a
      fraction of MLL5 located in the cytoplasm interacts with both RIG-I and its E3
      ubiquitin ligase STUB1, which promotes K48-linked polyubiquitination and
      proteasomal degradation of RIG-I. MLL5 deficiency attenuates the RIG-I and STUB1
      association, reducing K48-linked polyubiquitination and accumulation of RIG-I
      protein in cells. Upon virus infection, nuclear MLL5 protein translocates from
      the nucleus to the cytoplasm inducing STUB1-mediated degradation of RIG-I. Our
      study uncovers a previously unrecognized role for MLL5 in antiviral innate immune
      responses and suggests a new target for controlling viral infection.

PMID- 29593342
TI  - Genetic variants and pathways implicated in a pediatric inflammatory bowel
      disease cohort.
AB  - In the United States, approximately 5% of individuals with inflammatory bowel
      disease (IBD) are younger than 20 years old. Studies of pediatric cohorts can
      provide unique insights into genetic architecture of IBD, which includes Crohn's
      disease (CD) and ulcerative colitis (UC). Large genome-wide association studies
      have found more than 200 IBD-associated loci but explain a minority of disease
      variance for CD and UC. We sought to characterize the contribution of rare
      variants to disease development, comparing exome sequencing of 368 pediatric IBD
      patients to publicly available exome sequencing (dbGaP) and aggregate frequency
      data (ExAC). Using dbGaP data, we performed logistic regression for common
      variants and optimal unified association tests (SKAT-O) for rare, likely
      deleterious variants. We further compared rare variants to ExAC counts with
      Fisher's exact tests. We did pathway enrichment analysis on the most significant
      genes from each comparison. Many variants overlapped with known IBD-associated
      genes (e.g. NOD2). Rare variants were enriched in CD-associated loci (p = 0.009)
      and showed suggestive enrichment in neutrophil function genes (p = 0.05). Pathway
      enrichment implicated immune-related pathways, especially cell killing and
      apoptosis. Variants in extracellular matrix genes also emerged as an important
      theme in our analysis.

PMID- 29593343
TI  - Treatment in myositis.
AB  - As with the treatment of many immune-mediated diseases, managing myositis
      encompasses diverse factors, which present a challenge to the physician caring
      for these patients. The idiopathic inflammatory myopathies (IIMs, also known as
      myositis), are fundamentally heterogeneous; many contributory immunological
      perturbations are involved in the pathogenesis of myositis, leading to varying
      clinical phenotypic presentations. Targeting any one or several of these
      deleterious pathways with a therapeutic agent might seem reasonable, but the
      desired response is not uniformly predictable. The presence of many serious
      extramuscular manifestations, such as severe skin rash, interstitial lung disease
      and arthritis, complicates the management of myositis. Myositis is rare, and very
      few large treatment trial results are available to guide clinicians. Outcome
      measures to effectively gauge treatment responses have been available for only a
      few years, and response criteria that incorporate critical core set measures
      continue to evolve. Nevertheless, a multitude of immunosuppressive and
      immunomodulatory agents are available to clinicians managing myositis, and the
      emergence of biologic agents targeting potential pathogenic pathways offers hope
      for mitigating or curing this enigmatic group of diseases. Paradigm shifts in the
      nonpharmacological approach to treat myositis have also occurred as more
      aggressive exercise regimens have shown benefit in patients, even those with
      active disease.

PMID- 29593345
TI  - Building three-dimensional human brain organoids.

PMID- 29593346
TI  - Large regional disparities in prevalence, management and reimbursement of
      hospital undernutrition.
AB  - BACKGROUND/OBJECTIVES: Undernutrition is a frequent condition among hospitalized
      patients, with a significant impact on patient's outcome and hospital costs.
      Whether undernutrition is reported similarly at the national level has seldom
      been assessed. We aimed to (1) assess regional differences within Switzerland
      regarding undernutrition prevalence, management, and cost reimbursement and (2)
      identify the factors associated with reporting of undernutrition status and its
      management. SUBJECTS/METHODS: Observational cross-sectional study including
      routine statistics from the Swiss hospital discharge databases for years 2013 and
      2014 (seven administrative regions). All adults aged >=20 with length of hospital
      stay of at least 1 day was included. Reported undernutrition was defined based on
      the International Classification of Diseases (ICD)-10 codes. Nutritional
      management and "reimbursable" undernutrition codes were also assessed. RESULTS:
      Of the initial 1,784,855 hospitalizations, 3.6% had reported undernutrition, the
      prevalence ranging between 1.8% (Ticino) and 4.6% (Mittelland). Use of different
      undernutrition-related ICD-10 codes also varied considerably across regions.
      Multivariable analysis showed a twofold variation in reported undernutrition:
      multivariable-adjusted odds ratio and 95% confidence interval relative to Eastern
      Switzerland: 2.31 (2.23, 2.38) for Mittelland and 0.74 (0.70, 0.79) for Ticino.
      Over half (59.6%) of hospitalizations with reported undernutrition also included
      information on undernutrition management, ranging between 28.6% (Ticino) and
      67.2% (Zurich). Only one third (36.8%) of undernutrition-related codes were
      reimbursable, ranging between 8.3% (Ticino) and 50.7% (Zurich). CONCLUSIONS: In
      Switzerland, there is considerable regional variation regarding reporting of
      undernutrition prevalence, management, and cost reimbursement. Undernutrition
      appears to be insufficiently managed and valued.

PMID- 29593344
TI  - Characterization of Split Fluorescent Protein Variants and Quantitative Analyses
      of Their Self-Assembly Process.
AB  - Many biotechniques use complementary split-fluorescent protein (sFPs) fragments
      to visualize protein-protein interactions, image cells by ensemble or single
      molecule fluorescence microscopy, or assemble nanomaterials and protein
      superstructures. Yet, the reassembly mechanisms of sFPs, including fragment
      binding rates, folding, chromophore maturation and overall photophysics remain
      poorly characterized. Here, we evolved asymmetric and self-complementing green,
      yellow and cyan sFPs together with their full-length equivalents (flFPs) and
      described their biochemical and photophysical properties in vitro and in cells.
      While re-assembled sFPs have spectral properties similar to flFPs, they display
      slightly reduced quantum yields and fluorescence lifetimes due to a less sturdy
      beta-barrel structure. The complementation of recombinant sFPs expressed in vitro
      follows a conformational selection mechanism whereby the larger sFP fragments
      exist in a monomer-dimer equilibrium and only monomers are competent for
      fluorescence complementation. This bimolecular fragment interaction involves a
      slow and irreversible binding step, followed by chromophore maturation at a rate
      similar to that of flFPs. When expressed as fusion tags in cells, sFPs behave as
      monomers directly activated with synthetic complementary fragments. This study
      resulted in the development of sFP color variants having improved maturation
      kinetics, brightness, and photophysics for fluorescence microscopy imaging of
      cellular processes, including single molecule detection.

PMID- 29593347
TI  - The direct and indirect associations of usual free sugar intake on BMI z-scores
      of Australian children and adolescents.
AB  - This cross-sectional analysis aimed to assess the association between free sugar
      consumption and the BMI z-score of Australian children and adolescents. Data from
      the 2007 Australian National Children's Nutrition and Physical Activity Survey
      were analyzed. Structural equation modeling was used to assess the direct
      association between usual free sugar intake and age-and-sex-specific BMI z-score,
      and the indirect association mediated via energy overconsumption. Weak and
      statistically non-significant associations were found for the direct (BMI z-score
      beta = -0.02 per 10% change in energy intake from free sugar, p = 0.705) and
      indirect pathways (BMI z-score beta = -0.04 per 10% change in energy intake from
      free sugar, p = 0.705). We concluded that free sugar intake was not associated
      with BMI z-score in this cohort. Instead of focusing on a single energy source in
      the diet, improving the quality of the whole diet may be a better approach in
      tackling childhood obesity.

PMID- 29593348
TI  - Profiles of miRNA Isoforms and tRNA Fragments in Prostate Cancer.
AB  - MicroRNA (miRNA) isoforms ("isomiRs") and tRNA-derived fragments ("tRFs") are
      powerful regulatory non-coding RNAs (ncRNAs). In human tissues, both types of
      molecules are abundant, with expression patterns that depend on a person's race,
      sex and population origin. Here, we present our analyses of the Prostate Cancer
      (PRAD) datasets of The Cancer Genome Atlas (TCGA) from the standpoint of isomiRs
      and tRFs. This study represents the first simultaneous examination of isomiRs and
      tRFs in a large cohort of PRAD patients. We find that isomiRs and tRFs have
      extensive correlations with messenger RNAs (mRNAs). These correlations are
      disrupted in PRAD, which suggests disruptions of the regulatory network in the
      disease state. Notably, we find that the profiles of isomiRs and tRFs differ in
      patients belonging to different races. We hope that the presented findings can
      lay the groundwork for future research efforts aimed at elucidating the
      functional roles of the numerous and distinct members of these two categories of
      ncRNAs that are present in PRAD.

PMID- 29593349
TI  - Tlr1612 is the major repressor of cell aggregation in the light-color-dependent c
      di-GMP signaling network of Thermosynechococcus vulcanus.
AB  - Cyclic diguanylate (c-di-GMP) is a bacterial second messenger involved in
      sessile/motile lifestyle transitions. We previously reported that c-di-GMP is a
      crucial inducer of cell aggregation of the cyanobacterium Thermosynechococcus
      vulcanus. The three cooperating cyanobacteriochrome photoreceptors (SesA/B/C)
      regulate cell aggregation in a light color-dependent manner by
      synthesizing/degrading c-di-GMP. Although a variety of c-di-GMP signaling
      proteins are encoded in cyanobacterial genomes, how c-di-GMP signaling networks
      are organized remains elusive. Here we experimentally demonstrate that the
      cellulose synthase Tll0007, which is essential for cell aggregation, binds c-di
      GMP although the affinity is low (Kd = 63.9 +/- 5.1 uM). We also show that SesA
      the main trigger of cell aggregation-is subject to strict product feedback
      inhibition (IC50 = 1.07 +/- 0.13 uM). These results suggest that SesA-produced c
      di-GMP may not directly bind to Tll0007. We therefore systematically analyzed all
      10 of the genes encoding proteins containing a c-di-GMP synthesis/degradation
      domain. We identified Tlr1612, harboring both domains, as the major repressor of
      cell aggregation under the repressing teal-green light irradiation. tlr1612 acts
      downstream of sesA and is not regulated transcriptionally by light color,
      suggesting that Tlr1612 may be involved in c-di-GMP amplification in the
      signaling cascade. Post-transcriptional control is likely crucial for the light
      regulated c-di-GMP signaling.

PMID- 29593350
TI  - Elucidation of the bacterial communities associated with the harmful microalgae
      Alexandrium tamarense and Cochlodinium polykrikoides using nanopore sequencing.
AB  - Interactions between microalgae and bacteria are often obligatory for harmful
      algal blooms (HABs). Here, we investigated the specific bacterial communities
      associated with Alexandrium tamarense and Cochlodinium polykrikoides, which cause
      ecological and economic damage during their blooms. To this end, the bacterial
      metagenome was selectively isolated from the two dinoflagellates and subsequently
      used for 16S rRNA analysis via the Nanopore MinION and Illumina sequencing
      platforms. Although the full-length 16S rRNA reads from the MinION platform
      showed high correlation in higher taxonomic ranks to the partial-length 16S rRNA
      reads from the Illumina platform, there was less correlation at the genus and
      species levels. MinION reads that are similar in the V3-V4 hypervariable regions
      with Illumina reads are classified to different taxonomies due to the extra
      information encoded in the full-length 16S rRNA reads. This indicates that bias
      arising from the short length Illumina reads can be supplemented by MinION reads.
      Furthermore, integrated analysis of the Illumina and MinION data showed that A.
      tamarense was predominantly enriched in the Roseobacter clade and C.
      polykrikoides was enriched in Gammaproteobacteria and Alphaproteobacteria. These
      results suggest that the association of different bacterial communities with A.
      tamarense and C. polykrikoides may be required for HABs.

PMID- 29593351
TI  - "Possibly positive or certainly uncertain?": participants' responses to uncertain
      diagnostic results from exome sequencing.
AB  - PurposeClinical genome sequencing produces uncertain diagnostic results, raising
      concerns about how to communicate the method's inherent complexities in ways that
      reduce potential misunderstandings and harm. This study investigates clinicians'
      communications and patient/participant responses to uncertain diagnostic results
      arising from a clinical exome sequencing research study, contributing empirical
      data to the debate surrounding disclosure of uncertain genomic
      information.MethodsWe investigated the communication and impact of uncertain
      diagnostic results using ethnographic observations of result disclosures with 21
      adults and 11 parents of child patients, followed by two semistructured
      interviews with these same participants.ResultsParticipants understood their
      uncertain results in ways that were congruent with clinical geneticists'
      communications. They followed recommendations for further consultation, although
      family testing to resolve uncertainty was not always done. Participants were
      prepared for learning an uncertain result and grasped the key concept that it
      should not be used to guide health-care or other decisions. They did not express
      regret for having learned the uncertain result; most regarded it as potentially
      valuable in the future.ConclusionThis study suggests that uncertain diagnostic
      results from genome sequencing can be relayed to patients in ways they can
      understand and consistent with providers' interpretations, without causing undue
      harm.

PMID- 29593354
TI  - Ultra-fast responsive colloidal-polymer composite-based volatile organic
      compounds (VOC) sensor using nanoscale easy tear process.
AB  - There is an immense need for developing a simple, rapid, and inexpensive
      detection assay for health-care applications or monitoring environments. To
      address this need, a photonic crystal (PC)-based sensor has been extensively
      studied due to its numerous advantages such as colorimetric measurement, high
      sensitivity, and low cost. However, the response time of a typical PC-based
      sensor is relatively slow due to the presence of the inevitable upper residual
      layer in colloidal structures. Hence, we propose an ultra-fast responsive PC
      based volatile organic compound (VOC) sensor by using a "nanoscale easy tear
      (NET) process" inspired by commercially available "easy tear package". A
      colloidal crystal-polydimethylsiloxane (PDMS) composite can be successfully
      realized through nanoscale tear propagation along the interface between the outer
      surface of crystallized nanoparticles and bulk PDMS. The response time for VOC
      detection exhibits a significant decrease by allowing the direct contact with
      VOCs, because of perfect removal of the residual on the colloidal crystals.
      Moreover, vapor-phase VOCs can be monitored, which had been previously
      impossible. High-throughput production of the patterned colloidal crystal-polymer
      composite through the NET process can be applied to other multiplexed selective
      sensing applications or may be used for nanomolding templates.

PMID- 29593355
TI  - Severe maternal morbidity and related hospital quality measures in Maryland.
AB  - OBJECTIVE: To determine hospital characteristics and quality metrics associated
      with severe maternal morbidity (SMM) in Maryland. STUDY DESIGN: A population
      based observational study of 364,113 statewide delivery hospitalizations during
      2010-2015 linked with socio-economic community measures and hospital
      characteristics and quality measures. Multivariable logistic regression models
      with generalized estimating equations estimated SMM adjusting for individual,
      community, and hospital-level factors and clustering within hospitals and
      residence zip codes. RESULTS: The SMM prevalence was 197 per 10,000 deliveries.
      Adjusted SMM risk ratios were higher for younger (<20 years), older (35+ years),
      non-White non-Hispanic, unmarried, multiple substance users, women with multiple
      gestations, and chronic medical and mental health conditions than their
      counterparts. Communities with greater socio-economic disadvantage and hospitals
      with poorer patient experience and clinical care quality had higher rates of SMM.
      CONCLUSION: Addressing socio-economic disparities and improving quality of care
      in delivery hospitals are key to reducing the SMM burden in Maryland.

PMID- 29593356
TI  - Never judge a book by its cover: how NICU evaluators reach conclusions about
      quality of care.
AB  - OBJECTIVE: To identify key features in the NICU care delivery context that
      influence quality of care delivery. STUDY DESIGN: Qualitative study using in
      depth, semi-structured interviews with 10 NICU quality experts with extensive
      experience conducting NICU site visits and evaluating quality of care. Analyses
      were performed using the method of constant comparison based on grounded theory.
      RESULTS: Qualitative analysis yielded three major themes: (1) the foundation for
      high quality care is a cohesive unit culture, characterized by open
      communication, teamwork, and engagement of families; (2) effective linkages
      between measurement and improvement action is necessary for continuous
      improvement; and (3) NICU capacity for improvement is sustained by active
      support, exchange of skills, and resources from the hospital. CONCLUSIONS: Team
      cohesion, engagement of families, culture of improvement supported by measurement
      and institutional support from the hospital are some of the key contextual and
      managerial features critical to high-quality NICU care.

PMID- 29593357
TI  - Patterns of acute bilirubin encephalopathy in Nigeria: a multicenter pre
      intervention study.
AB  - BACKGROUND: Acute bilirubin encephalopathy (ABE) is an important cause of
      neonatal morbidity in Nigeria, accounting for 5-14% of neonatal deaths. Most
      newborns with severe ABE have irreversible damage before receiving treatment
      emphasizing the need for timely pre-admission monitoring and referral. There is
      limited evidence that educational interventions targeting mothers and health care
      providers will reduce delayed care. OBJECTIVE: To provide baseline data on the
      incidence of ABE and associated pre-admission risk factors in five centers of
      Nigeria in order to evaluate the effect of subsequent educational interventions
      on outcome. STUDY DESIGN: The incidence of ABE among newborns treated for
      hyperbilirubinemia was documented prospectively. Bivariate analysis and
      multivariate logistic regression were used to evaluate risk factors for acute
      bilirubin encephalopathy and reasons for regional differences in its occurrence.
      RESULTS: Of 1040 infants, 159 treated for hyperbilirubinemia (15.3%) had mild to
      severe bilirubin encephalopathy (including 35 deaths), but the incidence ranged
      from 7 to 22% between centers. Logistic regression identified four common
      predictors: total serum bilirubin (odds ratio 1.007 per mg/dl rise), out-of
      hospital births (OR 2.6), non-alloimmune hemolytic anemia (OR 2.8), and delayed
      care seeking (OR 4.3). CONCLUSION: The high occurrence of bilirubin
      encephalopathy in Nigeria is due in large part to a delay in seeking care. A
      planned intervention strategy will target conditions leading to severe
      hyperbilirubinemia and delay.

PMID- 29593358
TI  - Antitumor effect of antibiotic resistance gene-free plasmids encoding interleukin
      12 in canine melanoma model.
AB  - The electrotransfer of interleukin-12 (IL-12) has been demonstrated as an
      efficient and safe treatment for tumors in veterinary oncology. However, the
      plasmids used encode human or feline IL-12 and harbor the gene for antibiotic
      resistance. Therefore, our aim was to construct plasmids encoding canine IL-12
      without the antibiotic resistance genes driven by two different promoters:
      constitutive and fibroblast-specific. The results obtained in vitro in different
      cell lines showed that following gene electrotransfer, the newly constructed
      plasmids had cytotoxicity and expression profiles comparable to plasmids with
      antibiotic resistance genes. Additionally, in vivo studies showed a statistically
      significant prolonged tumor growth delay of CMeC-1 tumors compared to control
      vehicle-treated mice after intratumoral gene electrotransfer. Besides the higher
      gene expression obtained by plasmids with constitutive promoters, the main
      difference between both plasmids was in the distribution of the transgene
      expression. Namely, after gene electrotransfer, plasmids with constitutive
      promoters showed an increase of serum IL-12, whereas the gene expression of IL
      12, encoded by plasmids with fibroblast-specific promoters, was restricted to the
      tumor. Furthermore, after the gene electrotransfer of plasmids with constitutive
      promoters, granzyme B-positive cells were detected in the tumor and spleen,
      indicating a systemic effect of the therapy. Therefore, plasmids with different
      promoters present valuable tools for focused therapy with local or systemic
      effects. The results of the present study demonstrated that plasmids encoding
      canine IL-12 under constitutive and fibroblast-specific promoters without the
      gene for antibiotic resistance provide feasible tools for controlled gene
      delivery that could be used for the treatment of client-owned dogs.

PMID- 29593359
TI  - Magnetic nanoparticle-mediated gene therapy to induce Fas apoptosis pathway in
      breast cancer.
AB  - CD95 (Fas) is a complex integral protein that can be expressed in many cells. It
      induces apoptosis when interacted with its ligand CD95L (FasL). However, cancer
      cells are resistant to CD95-induced apoptosis because of the changes in death
      domain (DD) of CD95 (procaspase-8 and c-Flip). In this study, magnetic
      nanoparticles and lipid-based gene transfection methods were performed to provide
      active Fas expression in breast cancer cells. Plasmid DNA (pDNA), which can
      express both human Fas and GFP, was transfected to MCF-7 breast cancer cells.
      Expression of c-FLIP and caspase-8 and effect of monoclonal antibody FasL for
      apoptosis stimulation were investigated. Also transfection success of methods and
      effects on surface protein were compared. Western blot results indicated that MCF
      7 cells do not express caspase-8 but express large amount of c-FLIPL. Both lipid
      based and magnetic nanoparticle-mediated gene transfection methods successfully
      applied. Caspase-8 apoptosis pathway was activated on transfected cells. Magnetic
      nanoparticle-mediated gene transfer is a successful non-viral method for
      transfection, and it does not affect the expression of other cell proteins, such
      as beta actin and lamin-B1. The raised c-FLIPL concentration in cytosol inhibits
      apoptosis. However, transfection of CD95-GFP-tagged pDNA significantly increases
      apoptosis by activating caspase-8 pathway. FasL interaction indicated a slight
      increase of apoptosis in the transfected cells. The method and pDNA applied in
      this study have potentials to be used in gene therapy for breast cancer.

PMID- 29593360
TI  - From Die Traumdeutung to The Squiggle Game: A Brief History of an Evolution.
AB  - It is often possible to retrace the history of a new concept or a new technique,
      identifying precursor and reflections that would lay the foundations for the
      birth of something "new". This also applies to the "squiggle game" of Donald W.
      Winnicott, one of the Winnicottian "creations" in which the distinctive signs of
      its fatherhood are more evident as, at the same time, are evident several debts
      to other scientists: from Freud's interpretation of dreams, through Jung, Klein
      and Fordham to Milner's "free drawings".

PMID- 29593362
TI  - A Proposed Probabilistic Extension of the Halpern and Pearl Definition of 'Actual
      Cause'.
AB  - Joseph Halpern and Judea Pearl ([2005]) draw upon structural equation models to
      develop an attractive analysis of 'actual cause'. Their analysis is designed for
      the case of deterministic causation. I show that their account can be naturally
      extended to provide an elegant treatment of probabilistic causation.
      1Introduction2Preemption3Structural Equation Models4The Halpern and Pearl
      Definition of 'Actual Cause'5Preemption Again6The Probabilistic
      Case7Probabilistic Causal Models8A Proposed Probabilistic Extension of Halpern
      and Pearl's Definition9Twardy and Korb's Account10Probabilistic
      Fizzling11Conclusion.

PMID- 29593361
TI  - The Science of Firescapes: Achieving Fire-Resilient Communities.
AB  - Wildland fire management has reached a crossroads. Current perspectives are not
      capable of answering interdisciplinary adaptation and mitigation challenges posed
      by increases in wildfire risk to human populations and the need to reintegrate
      fire as a vital landscape process. Fire science has been, and continues to be,
      performed in isolated "silos," including institutions (e.g., agencies versus
      universities), organizational structures (e.g., federal agency mandates versus
      local and state procedures for responding to fire), and research foci (e.g.,
      physical science, natural science, and social science). These silos tend to
      promote research, management, and policy that focus only on targeted aspects of
      the "wicked" wildfire problem. In this article, we provide guiding principles to
      bridge diverse fire science efforts to advance an integrated agenda of wildfire
      research that can help overcome disciplinary silos and provide insight on how to
      build fire-resilient communities.

PMID- 29593363
TI  - Political Ideology, Trust, and Cooperation: In-group Favoritism among Republicans
      and Democrats during a US National Election.
AB  - Theories suggest that political ideology relates to cooperation, with
      conservatives being more likely to pursue selfish outcomes, and liberals more
      likely to pursue egalitarian outcomes. In study 1, we examine how political
      ideology and political party affiliation (Republican vs. Democrat) predict
      cooperation with a partner who self-identifies as Republican or Democrat in two
      samples before (n = 362) and after (n = 366) the 2012 US presidential election.
      Liberals show slightly more concern for their partners' outcomes compared to
      conservatives (study 1), and in study 2 this relation is supported by a meta
      analysis (r = .15). However, in study 1, political ideology did not relate to
      cooperation in general. Both Republicans and Democrats extend more cooperation to
      their in-group relative to the out-group, and this is explained by expectations
      of cooperation from in-group versus out-group members. We discuss the relation
      between political ideology and cooperation within and between groups.

PMID- 29593364
TI  - THE ROLE OF PHYSICAL CAPITAL ASSETS IN YOUNG GIRLS' AND BOYS' MORTALITY AND
      GROWTH IN LOW- AND MIDDLE-INCOME COUNTRIES.

PMID- 29593365
TI  - (How) Does Obesity Harm Academic Performance? Stratification at the Intersection
      of Race, Sex, and Body Size in Elementary and High School.
AB  - In this study I hypothesize a larger penalty of obesity on teacher-assessed
      academic performance for white girls in English, where femininity is privileged,
      than in math, where stereotypical femininity is perceived to be a detriment. This
      pattern of associations would be expected if obesity largely influences academic
      performance through social pathways such as discrimination and stigma. In the
      Fragile Families and Child Wellbeing Study (~age 9) and the National Longitudinal
      Study of Youth 1997 (~age 18), I find obesity to be associated with a penalty on
      academic performance among white girls in English but not in math, while no
      association is found in either subject for white boys or for black students net
      of controls. Findings suggest that the relationship between obesity and academic
      performance may result largely from how educational institutions interact with
      bodies of different sizes, rather than primarily via constraints on physical
      health.

PMID- 29593366
TI  - The Emergence of Two Distinct Fertility Regimes in Economically Advanced
      Countries.
AB  - Beginning in 2000, in economically advanced countries, a remarkable bifurcation
      in fertility levels has emerged, with one group in the moderate range of period
      total fertility rates (TFR), about 1.9, and the other at 1.3. The upper branch
      consists of countries in Northern and Western Europe, Oceania and the United
      States; the lower branch includes Central, Southern and Eastern Europe, and East
      and Southeast Asia. A review of the major theories for low fertility countries
      reveals that none of them would have predicted this specific bifurcation. We
      argue that those countries with fertility levels close to replacement level have
      institutional arrangements, and related policies, that make it easier, not easy,
      for women to combine the worker and mother roles. The institutional details are
      quite different across countries, suggesting that multiple combinations of
      institutional arrangements and policies can lead to the same country-level
      fertility outcome. Canada, the only exception to this bifurcation, illustrates
      the importance of the different institutional structures in Quebec compared to
      the rest of Canada.

PMID- 29593367
TI  - A Case for "Reverse One-Child" Policies in Japan and South Korea? Examining the
      Link between Education Costs and Lowest-Low Fertility.
AB  - Household spending on children's pre-tertiary education is exceptionally high in
      Japan and South Korea, and has been cited as a cause of low fertility. Previous
      research attributes this high spending to a cultural emphasis on education in
      East Asian countries. In this paper, we argue that institutional factors, namely
      higher education and labor market systems, play an important role in reinforcing
      the pressure on parents to invest in their children's education. We review
      evidence showing that graduating from a prestigious university has very high
      economic and social returns in Japan and South Korea, and examine the
      implications for fertility within the framework of quantity-quality models.
      Finally, we put forward 'reverse one-child' policies that directly address the
      unintended consequences of these institutional factors on fertility. These
      policies have the additional virtues of having very low fiscal requirements and
      reducing social inequality.

PMID- 29593368
TI  - Man enough? Masculine discrepancy stress and intimate partner violence.
AB  - Research on gender roles suggests that men who strongly adhere to traditional
      masculine gender norms are at increased risk for the perpetration of violent and
      abusive acts toward their female intimate partners. Yet, gender norms alone fail
      to provide a comprehensive explanation of the multifaceted construct of intimate
      partner violence (IPV) and there is theoretical reason to suspect that men who
      fail to conform to masculine roles may equally be at risk for IPV. In the present
      study, we assessed effect of masculine discrepancy stress, a form of distress
      arising from perceived failure to conform to socially-prescribed masculine gender
      role norms, on IPV. Six-hundred men completed online surveys assessing their
      experience of discrepancy stress, masculine gender role norms, and history of
      IPV. Results indicated that masculine discrepancy stress significantly predicted
      men's historical perpetration of IPV independent of other masculinity related
      variables. Findings are discussed in terms of potential distress engendered by
      masculine socialization as well as putative implications of gender role
      discrepancy stress for understanding and intervening in partner violence
      perpetrated by men.

PMID- 29593369
TI  - Do Transnational Child-Raising Arrangements Affect Job Outcomes of Migrant
      Parents? Comparing Angolan Parents in Transnational and NonTransnational Families
      in the Netherlands.
AB  - Transnational family literature has established that parent-child separations
      affect negatively on the emotional well-being of migrant parents. Less attention
      has been paid to other effects separation can have on these parents' lives.
      Building on insights from transnational family studies and organizational
      psychology, this article explores the potential link between transnational family
      life and job outcomes. In particular, two potential negative outcomes are
      analyzed-job instability and job absenteeism-by comparing Angolan parents whose
      children live in Angola with Angolans who live with all their children in the
      Netherlands. Based on mechanisms identified by organizational psychology
      literature, mediation analysis is conducted. Results indicate that transnational
      family life increases the times migrant parents change jobs, which is partly
      mediated by low levels of happiness. Further analyses indicate that especially
      transnational parents who have limited contact with their children change jobs
      more often. No significant differences are found with regard to job absenteeism.

PMID- 29593370
TI  - Conflict Structures in Family Networks of Older Adults and Their Relationship
      With Health-Related Quality of Life.
AB  - This study explores the interrelationships between health-related quality of life
      and conflict structures in family networks of older adults. Data were derived
      from a sample of 2,858 elders (aged 65 years and older) from the
      Vivre/Leben/Vivere study, a large survey addressing family life and health
      conditions of older people in Switzerland. Conflict density in family networks
      and the betweenness centrality of respondents in family conflict are
      significantly associated with health-related quality of life measures.
      Furthermore, the results demonstrate that conflict-health associations are
      mediated by the level of perceived individual stress where psychological health
      is concerned. Family conflict structures depend to a large extent on family
      composition and age. This study stresses the importance of older adults actively
      shaping the composition of their family contexts in ways that promote both
      conflict and stress avoidance.

PMID- 29593371
TI  - The Ties That Bind: Materiality, Identity, and the Life Course in the "Things"
      Families Keep.
AB  - Using an interdisciplinary research methodology across three archaeological and
      historical case studies, this article explores "family archives." Four themes
      illustrate how objects held in family archives, curation practices, and
      intergenerational narratives reinforce a family's sense of itself: people-object
      interactions, gender, socialization and identity formation, and the "life
      course." These themes provide a framework for professional archivists to assist
      communities and individuals working with their own family archives. We argue that
      the family archive, broadly defined, encourages a more egalitarian approach to
      history. We suggest a multiperiod analysis draws attention to historical forms of
      knowledge and meaning-making practices over time.

PMID- 29593373
TI  - Exploring the use of situation awareness in behaviors and practices of health and
      safety leaders.
AB  - An understanding of how health and safety management systems (HSMS) reduce
      worksite injuries, illnesses and fatalities may be gained in studying the
      behaviors of health and safety leaders. These leaders bear the accountability for
      identifying, understanding and managing the risks of a mining operation. More
      importantly, they have to transfer this knowledge of perception, recognition and
      response to risks in the mining environment to their workers. The leaders'
      efforts to build and maintain a mining operation's workforce that consistently
      executes safe work practices may be captured through more than just lagging
      indicators of health and safety performance. This exploratory study interviewed
      six leaders in occupations such as site-level safety supervisors, mine
      superintendents and/or general managers at surface and underground stone, sand
      and gravel and metal/nonmetal mine sites throughout the United States, with
      employee populations ranging from 40 to 175. In exploring leaders' perspectives
      on how they systematically manage health and safety, examples such as approaches
      to task training, handling near-miss incidents, identifying future leaders and
      providing workers with feedback offer insights into how leaders translate their
      knowledge and management of site-level risks to others.

PMID- 29593372
TI  - Empirical Examinations of Modifications and Adaptations to Evidence-Based
      Psychotherapies: Methodologies, Impact, and Future Directions.
AB  - This review describes methods used to examine the modifications and adaptations
      to evidence-based psychological treatments (EBPTs), assesses what is known about
      the impact of modifications and adaptations to EBPTs, and makes recommendations
      for future research and clinical care. One hundred eight primary studies and
      three meta-analyses were identified. All studies examined planned adaptations,
      and many simultaneously investigated multiple types of adaptations. With the
      exception of studies on adding or removing specific EBPT elements, few studies
      compared adapted EBPTs to the original protocols. There was little evidence that
      adaptations in the studies were detrimental, but there was also limited
      consistent evidence that adapted protocols outperformed the original protocols,
      with the exception of adding components to EBPTs. Implications for EBPT delivery
      and future research are discussed.

PMID- 29593374
TI  - Examining the Prevalence and Predictors of Injury from Adolescent Dating
      Violence.
AB  - Medical needs of youth who experience dating violence are not well understood
      because of limited past research examining the prevalence and predictors of
      injuries and medical help seeking. To address these gaps, the current study
      described the prevalence and predictors of injuries from dating violence from
      grades 8 through 12 in a large sample of youth. Results indicate that one third
      to one half of youth who experienced any physical and/or sexual dating violence
      also sustained an injury. Prevalence of injury was highest in the 8th grade and
      was significantly higher for females than for males across grades 8 through 11.
      Youth who experienced greater amounts of violent victimization in their
      relationships (physical, sexual, and psychological) were at highest risk for
      injury. Results also suggest that victims at highest risk for injury are girls,
      white youth, those experiencing multiple types of violence, and those who also
      engage in perpetration. Given the high prevalence of injury among youth who
      report dating violence, healthcare professionals may be in a unique position to
      screen and counsel youth about dating violence. Because the highest prevalence of
      injury occurred before high school, prevention programs should start early and
      selected prevention may be used for youth at highest risk for injury.

PMID- 29593375
TI  - Chitosan Membrane Embedded With ZnO/CuO Nanocomposites for the Photodegradation
      of Fast Green Dye Under Artificial and Solar Irradiation.
AB  - Fast Green (FCF) dye is commonly used in both cytology and histology
      applications. Previous studies have found that it can cause mutagenic and
      tumorigenic effects in experimental human and animal populations. It can also be
      a source of skin, eye, respiratory, and digestive irritation. The purpose of this
      study was to examine the use of thin film membranes to degrade FCF. A thin film
      membrane of chitosan (CS) was fabricated and subsequently filled with zinc oxide
      nanoparticles (ZnO) or ZnO/CuO-heterostructured nanocomposites. The CS membrane
      was used as a matrix, and the nanomaterials were used as photocatalysts. The
      prepared membranes were characterised by four analytical techniques: atomic force
      microscopy, scanning electron microscopy, X-ray diffraction, and energy
      dispersive X-ray analyses. The photocatalytic activity of the fabricated
      membranes was evaluated by performing experiments in which aqueous solutions of
      FCF dye that contained the fabricated membrane were irradiated with solar light
      or UV light. The photodegradation percentage was spectrophotometrically
      determined by monitoring the maximum wavelengths (lambdamax) of FCF at 623 nm for
      different irradiation times. The decolourisation percentages of the dye under
      solar light were 57.90% and 60.23% using the CS-ZnO and CS-ZnO/CuO membranes,
      respectively. When UV light irradiation was employed as the source of
      irradiation, the photodegradation percentages of FCF were 71.45% and 91.21% using
      the CS-ZnO and CS-ZnO/CuO membranes, respectively. These results indicated that
      the best photocatalytic system for the degradation of FCF dye was CS-ZnO/CuO
      membrane in combination with UV light irradiation. The study also found that it
      was easy to separate the prepared membranes after the reaction without the need
      for a centrifuge or magnet. The results demonstrate the potential for CS-ZnO and
      CS-ZnO/CuO membranes for use as effective sorbents during the process of
      photodegradation of harmful dyes within waste water recycling practices.

PMID- 29593376
TI  - Clinical and virological analysis of epidemic keratoconjunctivitis caused by
      adenovirus type 54 in a regional ophthalmic clinic in Kyushu, Japan.
AB  - Background: Human adenovirus type 54 (HAdV-54) is a novel type of adenovirus that
      belongs to species D and has thus far been detected only in Japan in patients
      with epidemic keratoconjunctivitis (EKC). There was a large nationwide outbreak
      of HAdV-54 EKC from 2015 to 2016 in Japan. The clinical characteristics of an
      outbreak of HAdV-54 conjunctivitis treated in a regional ophthalmic clinic in
      Fukuoka, Japan, in 2016 were analyzed. Patients and methods: A consecutive series
      of 55 cases diagnosed clinically as EKC confirmed by HAdV-54 detection from
      conjunctival scrapings by polymerase chain reaction (PCR) method between 17 June
      2016 and 29 August 2016 were enrolled. Viral DNA copies were counted by real-time
      PCR method. The clinical findings were recorded at the first visit to the clinic
      and evaluated. Results: In the analysis of the relationship between mean clinical
      score groups and several factors, such as days after onset, sex, HAdV DNA number
      on a logarithmic scale, and age, most factors did not show a significant
      difference in clinical score between groups. However, mean clinical score of
      cases aged <23 years was significantly higher than that of cases aged >=23 years
      (P<0.01). The correlation coefficient between DNA copies on a logarithmic scale
      and clinical score was 0.280, and a significant correlation was observed
      (P<0.05). Multiple subepithelial corneal infiltrates (MSI) were observed in 24
      out of 31 cases (77%). Conclusion: These results suggested that the clinical
      features in the early phase of HAdV-54 keratoconjunctivitis were milder but the
      rate of MSI observed in the late phase was higher than those in previous
      epidemics of several HAdV types. The significant difference in clinical severity
      between age groups might be a virological characteristic of HAdV-54.

PMID- 29593378
TI  - Comparative study of induced changes in effective lens position and refraction
      after Nd:YAG laser capsulotomy according to intraocular lens design.
AB  - Purpose: To evaluate and compare the changes in refraction and effective
      intraocular lens (IOL) position between a plate-haptic IOL and a c-loop single
      piece IOL after neodymium-doped yttrium aluminium garnet (YAG) laser posterior
      capsulotomy. Methods: In a prospective study, anterior chamber depth and
      subjective refraction were measured in 110 pseudophakic eyes from 110 patients,
      before and 1 month after YAG laser capsulotomy. Patients were divided into 2
      groups according to the IOL design: group 1 (plate-haptic acrylic hydrophilic AT
      LISA tri 839MP(r)) and group 2 (c-loop acrylic hydrophobic single-piece
      AcrySof(r) SA60AT). Lens position was obtained through optical coherence biometry
      (Biograph WaveLight OB820(r)). Results: YAG laser capsulotomy was performed
      37.8+/-9.8 months after surgery in group 1 and 40.6+/-8.6 months in group 2
      (p=0.125). Significant changes were found in the lens effective position after
      treatment in the 2 groups. The YAG posterior capsulotomy led to a change of
      anterior chamber depth in group 1 from 4.03+/-0.32 mm to 3.86+/-0.34 mm (p=0.02)
      and in group 2 from 4.03+/-0.37 mm to 4.14+/-0.45 mm (p=0.025). After YAG laser
      posterior capsulotomy, no significant changes were observed in mean spherical
      equivalent, sphere or cylinder for both groups (p>0.05). Conclusion: YAG laser
      posterior capsulotomy can induce a significant change in the IOL position
      according to the IOL type; however, the refractive change after treatment is
      clinically insignificant.

PMID- 29593377
TI  - Management of chronic ocular sarcoidosis: challenges and solutions.
AB  - Background: Sarcoidosis constitutes one of the leading causes of ocular
      inflammation. Chronic ocular sarcoidosis can affect any segment of the eye and
      its adnexa, producing a wide range of clinical manifestations and severity. If
      left untreated, permanent visual impairment or even blindness may ensue.
      Treatment approaches vary from topical therapy to systemic agents that induce
      immunosuppression to different levels according to disease severity. Objective:
      To review the published literature on the management options for chronic ocular
      sarcoidosis and provide a comprehensive list of available treatment strategies,
      including the newer biologics. Summary: Ocular disease remains a challenging
      aspect of sarcoidosis and may even be the presenting sign of the disease. Prompt
      and effective therapy may reverse visual damage and prevent permanent loss of
      vision. Because of the complexity of the disease, a multidisciplinary approach is
      often required, with a view to addressing both the ocular and other systemic
      manifestations of sarcoidosis. Recent data suggest that achieving overall optimal
      systemic control is of paramount importance in controlling eye inflammation as
      well. Cytotoxic immunosuppressive agents for refractory chronic ocular disease,
      as well as biologic anti-TNFalpha therapies, have advanced the management of
      chronic disease and should be considered corticosteroid-sparing strategies before
      the onset of significant steroid-induced morbidity.

PMID- 29593379
TI  - The clinical effectiveness of tafluprost on Japanese normal-tension glaucoma
      patients.
AB  - Purpose: This study evaluates the effect of tafluprost on visual field
      progression in normal-tension glaucoma (NTG) in a Japanese population under daily
      clinical practice settings. Patients and methods: This is a post-marketing,
      multicenter, non-interventional, observational study. Patients with NTG who
      initiated tafluprost treatment were registered and prospectively observed for 2-3
      years to investigate its effectiveness on visual field progression and
      intraocular pressure (IOP) and safety in Japan. Visual field progression was
      evaluated using mean deviation (MD) slopes in a visual field analysis set that
      comprised patients with reliable Humphrey visual fields taken at 5 or more time
      points throughout the 2-3 years. Results: Of the 1,454 patients registered from
      160 medical institutions, 1,353 were set for safety analysis and 416 were set for
      visual field analysis. Due to insufficient effectiveness or safety reasons 194
      patients discontinued tafluprost, and 388 patients discontinued tafluprost due to
      being lost to follow-up or another reason. The MD slopes were -0.09+/-0.85
      dB/year in the entire visual field analysis set, -0.02+/-0.80 dB/year in naive
      monotherapy patients, -0.07+/-0.68 dB/year in switching monotherapy patients, and
      -0.32+/-1.04 dB/year in concomitant therapy patients. In naive monotherapy, a
      significant difference in MD slopes was observed between patients with an IOP
      reduction of 10% or higher (0.11+/-0.73 dB/year) vs patients with an IOP
      reduction of <10% (-0.22+/-0.87 dB/year). Significant differences were also
      observed in the subset analyses when the patients were divided by both MD and IOP
      at baseline, and presence of vitreoretinal concomitant disease. The adverse
      reactions were observed in 9.53% patients without any serious adverse reactions.
      Conclusion: An at least 10% IOP reduction with tafluprost monotherapy in 56.7% of
      the treatment-naive NTG eyes was sufficient to significantly reduce the MD rate
      of progression.

PMID- 29593380
TI  - Bioequivalence of a biosimilar enoxaparin sodium to Clexane(r) after single 100
      mg subcutaneous dose: results of a randomized, double-blind, crossover study in
      healthy volunteers.
AB  - Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence
      of a biosimilar enoxaparin to the reference drug, and to assess its safety and
      tolerability in healthy volunteers. Patients and methods: A randomized, double
      blind, crossover, 2-sequence, single-dose study was conducted in healthy
      volunteers of both sexes. Participants were sequentially and randomly
      administered single subcutaneous injections of enoxaparin 100 mg manufactured by
      Rovi (test; Madrid, Spain) and Clexane(r) (enoxaparin 100 mg manufactured by
      Sanofi, reference) separated by a 1-week washout period. The primary PK/PD
      variables were maximum activity (Amax) and area under the effect curve from time
      0 to the last measured activity (T) (AUEC0-T) and AUEC from time 0 to infinity
      (AUEC0-inf) of anti-FXa activity, and Amax and AUEC0-T of anti-FIIa activity.
      Secondary variables were Amax and AUEC0-T, AUEC0-inf of tissue factor pathway
      inhibitor, and the ratio of AUEC0-T anti-FXa to anti-FIIa activity. Biosimilarity
      would be shown when the 95% CI of the ratio of geometric least squares means (95%
      CI RGLSMs) of primary PK/PD parameters fell within the standard range of
      bioequivalence, ie, 80%-125%. Results: The study sample consisted of 46
      volunteers (33 males) aged 18-44 years and with body mass index ranging from 19.0
      to 31.1 kg/m2. Three subjects did not complete the study. The curves of anti-FXa,
      anti-FIIa and tissue factor pathway inhibitor activities corresponding to
      administration of the test and reference products were comparable. The 95% CI
      RGLSMs of Amax, AUEC0-T and AUEC0-inf for anti-FXa activity were 94.6%-105.9%,
      99.8%-108.0% and 100.0%-108.6% respectively; Amax and AUEC0-T for anti-FIIa
      activity were 94.7%-112.6% and 90.9%-117.9% respectively. In addition, the 95% CI
      RGLSMs of all secondary variables fell within the range 80%-125%. The incidence
      and types of adverse events after administration of the test and reference drugs
      were similar. Conclusion: The results conclusively showed that the enoxaparin
      manufactured by Rovi is equivalent to the reference enoxaparin in all primary and
      secondary PK/PD parameters, as required by the European Medicines Agency to grant
      marketing authorization to a biosimilar low molecular-weight heparin.

PMID- 29593381
TI  - The hydroxypropyl-beta-cyclodextrin complexation of toltrazuril for enhancing
      bioavailability.
AB  - Introduction: Toltrazuril (Tol) is used to prevent and combat coccidiosis.
      However, its low aqueous solubility and poor oral bioavailability limit clinical
      application. Methods: To overcome the shortcomings, toltrazuril-hydroxypropyl
      beta-cyclodextrin inclusion complex (Tol-HP-beta-CD) was prepared and
      characterized. The comparative plasma disposition kinetics of Tol was analyzed
      after a single orally administered dose of 10 mg/kg Tol or Tol-HP-beta-CD in
      rabbits. Solution-stirring method was selected to prepare the inclusion complex.
      Complex formation was characterized by thin-layer chromatography, Fourier
      transform infrared spectrophotometry, and 1H nuclear magnetic resonance
      spectroscopy. In plasma profile, plasma samples were collected between 1 and 10
      days following administration. Plasma Tol concentrations were determined by high
      performance liquid chromatography. Results: In rabbit plasma, the time to peak
      concentration (Tmax) of Tol-HP-beta-CD was shorter than that of Tol (12 h vs 24
      h). Cmax (19.92+/-1.02 MUg/mL) and area under the concentration-time curve (AUC0
      infinity, 1,176.86+/-70.26 mg/L h) of the Tol-HP-beta-CD group significantly
      increased (p,0.01) than those of the Tol group (Cmax, 8.02+/-1.04 MUg/mL; AUC0
      infinity, 514.03+/-66.65 mg/L h). Conclusion: It can be concluded that the Tol-HP
      beta-CD increased the aqueous solubility and enhanced the oral bioavailability in
      rabbits. Complexation with HP-beta-CD is a feasible way to prepare a rapidly
      absorbed and more bioavailable Tol oral product.

PMID- 29593383
TI  - "I did not want to take that medicine": African-Americans' reasons for diabetes
      medication nonadherence and perceived solutions for enhancing adherence.
AB  - Background: Diabetes is disproportionally burdensome among African-Americans
      (AAs) and medication adherence is important for optimal outcomes. Limited studies
      have qualitatively examined reasons for nonadherence among AAs with type 2
      diabetes, though AAs are less adherent to prescribed medications compared to
      whites. This study explored the reasons for medication nonadherence and adherence
      among AAs with type 2 diabetes and examined AAs' perceived solutions for
      enhancing adherence. Methods: Forty AAs, age 45-60 years with type 2 diabetes for
      at least 1 year prior, taking at least one prescribed diabetes medication,
      participated in six semistructured 90-minute focus groups. Using a phenomenology
      qualitative approach, reasons for nonadherence and adherence, as well as
      participants' perceived solutions for increasing adherence were explored.
      Qualitative content analysis was conducted. Results: AAs' reasons for intentional
      nonadherence were associated with 1) their perception of medicines including
      concerns about medication side effects, as well as fear and frustration
      associated with taking medicines; 2) their perception of illness (disbelief of
      diabetes diagnosis); and 3) access to medicines and information resources.
      Participants reported taking their medicines because they valued being alive to
      perform their social and family roles, and their belief in the doctor's
      recommendation and medication helpfulness. Participants provided solutions for
      enhancing adherence by focusing on the roles of health care providers, patients,
      and the church. AAs wanted provider counseling on the necessity of taking
      medicines and the consequences of not taking them, indicating the need for the AA
      community to support and teach self-advocacy in diabetes self-management, and the
      church to act as an advocate in ensuring medication use. Conclusion: Intentional
      reasons of AAs with type 2 diabetes for not taking their medicines were related
      to their perception of medicines and illness. Solutions for enhancing diabetes
      medication adherence among AAs should focus on the roles of providers, patients,
      and the church.

PMID- 29593382
TI  - Tendinopathy: injury, repair, and current exploration.
AB  - Both acute and chronic tendinopathy result in high morbidity, requiring
      management that is often lengthy and expensive. However, limited and conflicting
      scientific evidence surrounding current management options has presented a
      challenge when trying to identify the best treatment for tendinopathy. As a
      result of shortcomings of current treatments, response to available therapies is
      often poor, resulting in frustration in both patients and physicians. Due to a
      lack of understanding of basic tendon-cell biology, further scientific
      investigation is needed in the field for the development of biological solutions.
      Optimization of new delivery systems and therapies that spatially and temporally
      mimic normal tendon physiology hold promise for clinical application. This review
      focuses on the clinical importance of tendinopathy, the structure of healthy
      tendons, tendon injury, and healing, and a discussion of current approaches for
      treatment that highlight the need for the development of new nonsurgical
      interventions.

PMID- 29593384
TI  - Cross-cultural adaptation and validation of the Arabic version of the Physical
      Activity Scale for the Elderly among community-dwelling older adults in Saudi
      Arabia.
AB  - Purpose: Older adults are the fastest growing population group worldwide. Regular
      physical activity (PA) is reported to reduce the risk of health conditions and
      improve personal well-being. Few validated instruments can be used to measure the
      PA levels among older adults in Saudi Arabia. The Physical Activity Scale for the
      Elderly (PASE) is used worldwide for evaluating the PA levels of the elderly in
      epidemiological studies. However, this scale has not been translated into Arabic.
      This study aimed to cross-culturally adapt the PASE into Arabic language and
      evaluate its reliability and validity among community-dwelling older adults in
      Saudi Arabia. Patients and methods: This study was a cross-sectional one
      following Beaton guidelines to translate and perform cultural adaptation, as well
      as test the reliability and validity of the PASE Arabic version (PASE-A). Elderly
      (N=74) people from both genders, who lived in a community dwelling in Riyadh
      city, were selected from several primary health care centers. The study used
      Cronbach's alpha coefficient to assess the internal consistency reliability,
      while intraclass correlation coefficient (ICC2,1) was used for test-retest
      reliability and the Spearman's rank correlation coefficient (r) was used to
      evaluate the correlation among PASE-A and grip strength, Timed Up and Go test,
      body mass index, and fat percentage. Results: Out of 74 older adults, 59 (79.7%)
      completed the PASE-A questionnaire twice. The internal consistency of the PASE-A
      components was good (Cronbach's alpha 0.70-0.75), and the reliability of the
      components was excellent (ICC2,1 0.90-0.98). A higher PASE-A score was associated
      with higher grip strength (r=0.28, p=0.05) and with shorter Timed Up and Go test
      times (r=-0.45, p=0.01). Conclusion: The PASE-A version was easy, understandable,
      and relevant for Saudi older adults' culture. This scale was a reliable and valid
      tool for evaluating and assessing the PA level among community-dwelling older
      adults in Saudi Arabia.

PMID- 29593385
TI  - Biological age as a health index for mortality and major age-related disease
      incidence in Koreans: National Health Insurance Service - Health screening 11
      year follow-up study.
AB  - Purpose: A comprehensive health index is needed to measure an individual's
      overall health and aging status and predict the risk of death and age-related
      disease incidence, and evaluate the effect of a health management program. The
      purpose of this study is to demonstrate the validity of estimated biological age
      (BA) in relation to all-cause mortality and age-related disease incidence based
      on National Sample Cohort database. Patients and methods: This study was based on
      National Sample Cohort database of the National Health Insurance Service -
      Eligibility database and the National Health Insurance Service - Medical and
      Health Examination database of the year 2002 through 2013. BA model was developed
      based on the National Health Insurance Service - National Sample Cohort (NHIS -
      NSC) database and Cox proportional hazard analysis was done for mortality and
      major age-related disease incidence. Results: For every 1 year increase of the
      calculated BA and chronological age difference, the hazard ratio for mortality
      significantly increased by 1.6% (1.5% in men and 2.0% in women) and also for
      hypertension, diabetes mellitus, heart disease, stroke, and cancer incidence by
      2.5%, 4.2%, 1.3%, 1.6%, and 0.4%, respectively (p<0.001). Conclusion: Estimated
      BA by the developed BA model based on NHIS - NSC database is expected to be used
      not only as an index for assessing health and aging status and predicting
      mortality and major age-related disease incidence, but can also be applied to
      various health care fields.

PMID- 29593387
TI  - Nanoantibiotics: strategic assets in the fight against drug-resistant superbugs.
AB  - Antimicrobial characteristics of metals reveal that Ag despite its economic
      constraints remains the most popular antibiotic agent. Antimicrobial
      characteristics of copper nanoparticles (CNPs) are not well understood. To our
      knowledge, no systematic comparative study on microbial properties of silver
      nanoparticles (SNPs) and CNPs exists. In this article, a comparative study on
      microbial properties of engineered metal nanoantibiotics against clinically
      important strains has been attempted. Our results indicate that biocidal
      activities of CNPs are better than SNPs. Minimum inhibitory concentration (MIC)
      values of CNPs are 10 times lower than the corresponding MICs of SNPs. These
      improved biocidal activities of CNPs would make it affordable and potent
      nontraditional antibiotics against which microbes are least susceptible to
      develop any drug resistance.

PMID- 29593386
TI  - Lack of association between airflow limitation and recurrence of venous
      thromboembolism among cancer patients with pulmonary embolism.
AB  - Background: COPD is a well-known risk factor for venous thromboembolism (VTE)
      development. However, recent data showed that it was not associated with VTE
      recurrence risk, which excluded cancer patients. This study investigated the
      association of airflow limitation and VTE recurrence in cancer patients with
      pulmonary embolism (PE). Methods: This is a retrospective cohort study of cancer
      patients with newly diagnosed PE at a university hospital. PE was confirmed using
      contrast-enhanced computed tomography scan. Airflow limitation was defined as pre
      bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity
      (FVC) <0.7 within 2 years of PE diagnosis. VTE recurrence was defined as a
      composite of recurrence as PE or deep vein thrombosis or both. Results: Among 401
      cancer patients with newly diagnosed PE, spirometry-based airflow limitation was
      observed in 126 (31.4%) patients. Half of the patients had lung cancer, which was
      more common in the group with airflow limitation (65.1% vs 42.9%, p < 0.001).
      Symptomatic PE was present in less than half (45.4%) of the cases, and 62.6% of
      patients were treated for PE. During the median follow-up period of 9.7 months,
      VTE recurred in 49 (12.2%) patients. Compared with patients without airflow
      limitation, those with airflow limitation did not have an increased risk of VTE
      recurrence in univariate or multivariate analyses (adjusted hazard ratio, 1.29
      [95% CI 0.68, 2.45]). Conclusion: The presence of airflow limitation did not
      increase the risk of VTE recurrence in cancer patients with PE. Prospective
      studies are needed to validate this finding.

PMID- 29593388
TI  - Iron oxide-doped niosomes as drug carriers for magnetically targeted drug
      delivery.
AB  - Magnetism has wide applications in various fields, such as diagnostics, drug
      targeting, molecular biology, cell isolation, cell purification, hyperthermia,
      and radioimmunoassay. In this study, we synthesized niosomes doped with iron
      oxide nanoparticles and a fluorophore for potential applications in magnetically
      targeted drug delivery. Release kinetics of the fluorophore and cytotoxicity were
      assessed. The results demonstrate that niosomes doped with iron oxide
      nanoparticles can serve as proficient and effective drug carriers in magnetically
      targeted drug delivery.

PMID- 29593389
TI  - Liposome encapsulation of doxorubicin and celecoxib in combination inhibits
      progression of human skin cancer cells.
AB  - Therapeutic agents aimed at inhibiting a single molecular target have not been
      successful in cancer therapy, but rather they impart resistance. However, multi
      target inhibitors have shown promising results in circumventing the development
      of resistance and inducing apoptosis in cancer cells/tissues. In this study, we
      encapsulated doxorubicin and celecoxib in a single liposome at a ratio of 1:10.
      These dual drug-encapsulated liposomes showed excellent anticancer activity
      compared to individually encapsulated liposomes. The expression of key proteins
      such as AKT and COX-2 was suppressed, which suggests that doxorubicin and
      celecoxib synergistically inhibit multiple key signaling pathways.

PMID- 29593390
TI  - Fluorescent gold nanoclusters for efficient cancer cell targeting.
AB  - Well-known surface properties of gold nanoparticles (AuNPs) offer easy surface
      modification with desired biomolecule, thus enabling them to be used for
      targeting and imaging of cancer cells/tissues. However, targeting and imaging
      capability come through after synthesis coating of AuNPs' surface with targeting
      or imaging molecules. Attempts have been made to conjugate both imaging and
      targeting molecules over the AuNPs, but have seen limited success. Hence,
      exploiting the fluorescence properties of gold nanoclusters (AuNCs), we have
      synthesized glucose-coated AuNCs for exhibiting both the imaging and targeting
      properties. These clusters have shown rapid and selective uptake in cancerous
      (A549) cells when compared with bovine serum albumin-coated AuNCs.

PMID- 29593391
TI  - Removal of pesticide toxicity by cysteine-capped Ag nanoparticles and study of
      their adsorption kinetics.
AB  - A new method has been developed for one-step synthesis of cysteine-capped Ag
      nanoparticles. The particles have been characterized by several techniques,
      including ultraviolet-visible spectroscopy, infrared spectroscopy, X-ray
      diffraction, scanning electron microscopy, and transmission electron microscopy.
      The interaction of these nanoparticles has been seen with two pesticides, namely,
      chlorpyrifos and malathion, which are major water pollutants.

PMID- 29593392
TI  - Oral bioavailability enhancement of agomelatine by loading into nanostructured
      lipid carriers: Peyer's patch targeting approach.
AB  - Agomelatine (AGM) is a new antidepressant drug with a novel mechanism of action
      and fewer side effects compared with older antidepressants. AGM is a melatonin
      receptor (MT1 and MT2) agonist and 5-hydroxytryptamine receptor (5-HT2C)
      antagonist. In the present study, the enhancement of the oral bioavailability of
      AGM was formulated and loaded into nanostructured lipid carriers (NLCs), using
      ultrasonication method. In vitro and ex vivo drug release was performed using a
      dialysis bag and rat duodenum, respectively. Our pharmacodynamic study showed
      that AGM-NLCs are more efficacious than a pure drug and marketed product, and
      confocal microscopy revealed lymphatic uptake of AGM-NLCs. The present study
      concluded that the NLCs enhanced the oral bioavailability of AGM (6.5-fold) by
      avoiding its first-pass metabolism by way of lymphatic uptake.

PMID- 29593393
TI  - Cellular internalization and antioxidant activity of cerium oxide nanoparticles
      in human monocytic leukemia cells.
AB  - Overproduction of free radicals contributes to oxidative stress and inflammation
      leading to various disease conditions. Cerium oxide nanoparticles (nanoceria)
      have been shown to scavenge free radicals and have the potential for being used
      as a therapeutic agent in disease conditions. Therefore, in the present study,
      human monocytic leukemia cells (THP-1) were used as a model to evaluate the
      uptake and free radical scavenging activity of nanoceria. Our data showed a
      significant (P<0.05) increase in the internalization of nanoceria in a
      concentration-dependent (10-100 ug/mL) manner in THP-1 cells. Although no
      cytotoxicity was observed at these concentrations, nanoceria significantly
      (P<0.05) reduced the amount of reactive oxygen species. This was evident by a
      significant (P<0.05) decrease in the 2,7-dichlorofluorescein diacetate
      fluorescence observed in flow cytometry and fluorescence microscopy. The present
      study shows that nanoceria have therapeutic potential in diseases such as cancer.

PMID- 29593394
TI  - Titanium dioxide nanoparticle-protein interaction explained by docking approach.
AB  - Titanium dioxide has been proven for toxicity by in vitro and in vivo approaches,
      however, further studies are needed in nano-toxicological research using in
      silico analysis. In this study, Autodock 4.0.5 was used in an attempt to evaluate
      the interaction of titanium dioxide with proteins. Different cellular proteins
      were sorted to study the interaction, binding sites, and active sites as a
      pocket. These pockets have been determined using CastP - an online server. The
      analysis for the docked structures was performed with regard to the most
      efficient binding with amino acids. This study is the first of its kind to report
      on the in silico docking interaction of titanium dioxide nanoparticles without
      any surface modification. The higher negative binding energy shows strong binding
      of titanium dioxide with proteins. A strong interaction with different cellular
      proteins was observed, and more specifically, titanium dioxide nanoparticles
      showed frequent interaction with proline, lysine, as well as leusine.

PMID- 29593395
TI  - Liposomal formulation of vitamin A for the potential treatment of osteoporosis.
AB  - Vitamin A targeting to bones is a suitable treatment for osteoporosis. In this
      study, we have developed vitamin A-encapsulated liposomes that can be useful to
      deliver vitamin A to the bones in a selective manner. This liposomal formulation
      of vitamin A has been found to be stable for >6 months as no significant change
      in size and charge occurred. Vitamin A liposomes-induced cell proliferation in
      SaOS-2 (human osteosarcoma cell line) and release kinetics study concluded that
      the liposomal formulation of vitamin A gives a controlled release of vitamin A in
      comparison to the free vitamin. The MTT assay showed the proliferation of SaOS-2
      cells after their treatment with vitamin A liposomes.

PMID- 29593396
TI  - Patterning artificial lipid bilayer on nanostructured surfaces.
AB  - Artificial lipid bilayer on solid substrate plays an important role as an
      interface between nanotechnology and biology. In this study, grid structures were
      patterned on Au-Nb-glass substrate and artificial bilayer was prepared on these
      structures. The fluidity was checked using fluorescence recovery after
      photobleaching (FRAP), and neuronal adhesion was monitored on such structure
      using EphrinA5-tethered lipid bilayer. EphrinA5 is a ligand that binds to the Eph
      receptors of rat cortical neurons and influences cellular adhesion. Our result
      elucidated that influence of these nanopatterned protein-tethered lipid bilayer
      on cellular guidance and signaling can address many underlying mechanisms of
      cellular functioning and help us to understand and differentiate the signaling
      procedure in cancer and neurodegenerative diseases.

PMID- 29593397
TI  - In vitro analysis of PARP inhibitor nanoformulations.
AB  - PARP-l is a DNA repair protein that plays a role in a number of repair pathways
      and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such
      as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an
      accumulation of deleterious mutations leading to genetic instability as a result
      of a number of cell replications. Currently, olaparib is only available in an
      oral form and has poor bioavailability, consequently leading to poor accumulation
      in the tumor due to first-pass metabolism. Therefore, in the present study, an
      injectable nanoparticle formulation of olaparib was created that offers a
      delivery route in which the drug would be fully bioavailable in the vasculature,
      suggesting greater tumor accumulation. Our results illustrated that injectable
      nanoformulations of olaparib and BMN-673, a next generation PARPi, could be
      developed, and an efficacy test indicated that BMN-673 is a much more potent
      PARPi than olaparib. The success of these molecular inhibitors as a monotherapy
      in inhibiting colony formation suggests enhanced efficacy of these treatments in
      combination with other therapies, even in tumors which have developed resistance.

PMID- 29593398
TI  - Synthesis and in vitro studies of PLGA-DTX nanoconjugate as potential drug
      delivery vehicle for oral cancer.
AB  - Advances in nanotechnology have led to the design of multifunctional
      nanoparticles capable of cellular imaging, targeted drug delivery, and
      diagnostics for early cancer detection. We synthesized poly(lactic-co-glycolic
      acid) nanoparticles encapsulating a model radiosensitizing drug docetaxel
      accomplishing localized in situ delivery of the sensitizer to the tumor site. The
      synthesized nanoparticles have been characterized for their physicochemical
      properties. The in vitro cytotoxicity of drug-loaded nanoparticles has been
      studied on human tongue carcinoma cell line SCC-9 (ATCC-CRL-1629).

PMID- 29593399
TI  - Preferential binding of fullerene and fullerenol with the N-terminal and middle
      regions of amyloid beta peptide: an in silico investigation.
AB  - Amyloid beta (Abeta) deposits are implicated in the pathogenesis of debilitating
      neurodegenerative disorders such as Alzheimer's disease. In the present study,
      the interactions of carbon-based nanoparticles (NPs) such as fullerene and
      fullerenol having different surface chemistry with Abeta were investigated using
      molecular dynamics simulations and docking studies. A detailed analysis of
      docking results showed that in 68% of the Abeta conformations, fullerene and
      fullerenol showed interactions with the N-terminal region of the peptide.
      However, the high-affinity binding site (E=-48.31 kJ/mol) of fullerene resides in
      the hydrophobic middle region of the peptide, whereas fullerenol interacts
      favorably with the charged N-terminal region with a binding energy of -50.42
      kJ/mol. The above differences in binding could be attributed to the surface
      chemistry of fullerene and fullerenol. Moreover, the N-terminal and middle
      regions of Abeta play an important role in Abeta aggregation. Therefore, the
      binding of fullerene and fullerenol could inhibit amyloid aggregation. This
      information will be helpful in designing NPs for targeting amyloid-related
      disorders.

PMID- 29593400
TI  - Curcumin Ag nanoconjugates for improved therapeutic effects in cancer.
AB  - Curcumin has a broad spectrum of pharmacological activities, one of them is
      anticancer activity that is mediated through multiple mechanisms. The major
      disadvantage associated with the use of curcumin is its low bioavailability due
      to its poor aqueous solubility. Nanoformulations of curcumin provide an effective
      solution for this problem. In this study, we have synthesized curcumin Ag
      nanoconjugates and evaluated their anticancer potential.

PMID- 29593401
TI  - Synthesis of biocompatible iron oxide nanoparticles as a drug delivery vehicle.
AB  - Over the last decade, there has been growing interest in developing novel
      nanoparticles (NPs) for biomedical applications. A safe-by-design approach was
      used in this study to synthesize biocompatible iron oxide NPs. The size of the
      particles obtained was ~100 nm. Although these NPs were significantly (P<0.05)
      internalized in MCF-7 (human breast adenocarcinoma cell line) cells, no adverse
      effect was observed in the cells as assessed by cytotoxicity assays (neutral red
      uptake and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and cell
      cycle analysis. Our data demonstrate the potential of iron oxide NPs as a
      biocompatible carrier for targeted drug delivery.

PMID- 29593402
TI  - Cholic acid-modified polyethylenimine: in vitro and in vivo studies.
AB  - Low-molecular-weight polyethylenimine has lower cytotoxicity than high molecular
      weight polyethylenimine, but it is not an efficient transfection agent because of
      limitations of DNA delivery into the cytoplasm. Therefore, in the present study,
      the hydrophobic modification of low-molecular-weight polyethylenimine (PEI 2 kDa
      [PEI2]) by cholic acid (ChA) was performed to form PEI2-ChA, and in vitro and in
      vivo studies were performed. Results indicate that the nanoplexes of PEI2-ChA
      with gWIZ-GFP have greater transfection efficiency (27%) in NT8e cell lines as
      evaluated by flow cytometry and also observed by fluorescence imaging. The
      present study concluded that the transferrin-containing nanoplexes of PEI2-ChA
      conjugates with plasmid p53 warrant clinical trials in humans after exhaustive
      animal studies for use as a novel gene delivery system.

PMID- 29593403
TI  - Modification of porous polyethylene scaffolds for cell attachment and
      proliferation.
AB  - Synthetic polymers are widely researched for their use in tissue engineering.
      Control in size, surface area, pore size, and elasticity are the biggest
      advantages of using a man-made polymer. However, often the polymers are
      hydrophobic (do not encourage cell attachment); hence, it is hugely challenging
      to integrate them with the normal tissues. Herein, we have tried to overcome this
      disadvantage of polymers by coating them with citrate-stabilized gold
      nanoparticles and arginine. High-density polyethylene, upon multiple treatments,
      shows low water contact angle, which encourages cell attachment and proliferation
      in comparison to the untreated polymers.

PMID- 29593404
TI  - In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell
      toxicity of Candida albicans, an opportunistic pathogen.
AB  - Silver nanoparticles (AgNps) have attracted maximal attention among all metal
      nanoparticles, and the study of their biological properties has gained impetus
      for further medical adoption. This study evaluated the cellular and molecular
      mechanisms associated with the action of AgNps against an opportunistic pathogen,
      Candida albicans. Spherical, stable AgNp (average size 21.6 nm) prepared by a
      chemical reduction method showed minimum inhibitory concentration (required to
      inhibit the growth of 90% of organisms) at 40 MUg/mL. AgNps have been reported to
      induce oxidative stress-mediated programmed cell death through the accumulation
      of intracellular reactive oxygen species (ROS). However, this study demonstrated
      that intracellular levels of AgNp-induced ROS could be reversed by using
      antioxidant ascorbic acid, but the sensitivity of AgNp-treated Candida cells
      could not be completely reversed. Moreover, in addition to the generation of ROS,
      the AgNps were found to affect other cellular targets resulting in altered
      membrane fluidity, membrane microenvironment, ergosterol content, cellular
      morphology, and ultrastructure. Thus, the generation of ROS does not seem to be
      the sole major cause of AgNp-mediated cell toxicity in Candida. Rather, the
      multitargeted action of AgNps, generation of ROS, alterations in ergosterol
      content, and membrane fluidity together seem to have potentiated anti-Candida
      action. Thus, this "nano-based drug therapy" is likely to favor broad-spectrum
      activity, multiple cellular targets, and minimum host toxicity. AgNps, therefore,
      appear to have the potential to address the challenges in multidrug resistance
      and fungal therapeutics.

PMID- 29593405
TI  - Targeted delivery of mannosylated-PLGA nanoparticles of antiretroviral drug to
      brain.
AB  - Mannosylated polymeric nanoparticles (NPs) enable improvement of brain
      bioavailability and reduction of dosing due to efficient drug delivery at the
      target site. Mannose receptors are present on the surface of macrophages, and
      therefore, in this study, it is expected that mannosylated NPs of anti-human
      immunodeficiency virus drug may target the macrophages, which may improve the
      therapeutic outcome and reduce the toxicity of antiretroviral bioactives.
      Poly(lactic-co-glycolic acid) (PLGA) and mannosylated-PLGA NPs (Mn-PLGA NPs) were
      prepared and administered by intravenous route in a dose of 10 mg/kg. After
      predetermined time period, the pharmacokinetics and biodistribution of NPs were
      analyzed using high-performance liquid chromatography and confocal microscopy,
      respectively. Results of this study indicated that Mn-PLGA NPs would be a
      promising therapeutic system for efficient delivery of the drug into brain
      macrophages.

PMID- 29593406
TI  - Curcuminoid-loaded poly(methyl methacrylate) nanoparticles for cancer therapy.
AB  - Curcuminoids (Curs), oleoresins from Curcuma longa L., have known
      anticarcinogenic and anti-inflammatory properties, but high toxicity, poor
      aqueous solubility and susceptibility to degradation in body fluids are
      deterrents to their clinical administration. Poly(methyl methacrylate)
      nanoparticles (PMMA-NPs) are biocompatible and resilient and can entrap
      hydrophobic drugs. The present investigation is related to solubilizing Curs by
      incorporating them in these nanoparticles (NPs) and is related to a study
      comparing the anticarcinogenic effect of drug-loaded NPs with free Cur using lung
      cancer (A549) cell line. Freshly extracted oleoresins were post loaded in PMMA
      NPs prepared using emulsion polymerization. The presence of the three components
      of oleoresins was confirmed by thin-layer chromatography. The size and morphology
      of void and loaded NPs were determined by dynamic light scattering, scanning
      electron microscopy and transmission electron microscopy. The NPs were spherical
      with diameters of 192.66+/-5 nm (void) and 199.16+/-5 nm (loaded). Drug loading
      and encapsulation efficiency were 6% and 93%, respectively. From the Fourier
      transform infrared spectroscopy spectra, the characteristic absorption vibration
      of poly(methyl methacrylate) and the bands at 1,383, 1,233 and 962 cm-1 for Cur
      moiety were observed. Drug release up to 10 days was estimated in buffer, saline
      and serum. The highest release of ~55% in ~3 days was noted in buffer that
      exhibited the highest bioavailability. The in vitro anticancer activity of loaded
      drug was evaluated up to 72 hours by MTT assay using A549 cell line. Cellular
      uptake of dye-loaded NPs was visualized within 30 minutes of incubation. The
      results revealed that the dose- and time-dependent cell death in case of loaded
      PMMA-NPs was comparable to that of free Cur. According to the study, the drug
      loaded PMMA-NPs appear to be highly suitable for effective, localized and safe
      chemotherapy.

PMID- 29593407
TI  - In vitro cytotoxicity of GO-DOx on FaDu squamous carcinoma cell lines.
AB  - We have synthesized graphene oxide (GO) nanosheets using modified Hummer's method
      and conjugated it with doxorubicin (DOx), an anticancer drug. Drug release
      kinetics from GO-DOx conjugate indicated the drug release at acidic pH. MTT assay
      performed on FaDu hypopharyngeal cancer cell lines revealed that the GO-DOx
      nanoconjugate inhibited cell proliferation more efficiently compared with pure
      DOx. Preliminary results indicate the potential of designed GO-DOx drug conjugate
      for head and neck cancer.

PMID- 29593408
TI  - Synthesis and characterization of multifunctional gold nanoclusters for
      application in radiation therapy.
AB  - Gold nanoparticles, because of their high radiation absorption coefficient and
      efficient generation of secondary photoelectrons, have been predicted to enhance
      therapeutic efficacy in radiation therapy. However, high dose for effective
      treatment limits their use. We have synthesized multifunctional gold nanoclusters
      (GNCs) that can be used for imaging and radiation therapy. The designed GNCs have
      been characterized for their physicochemical properties, biocompatibility, and
      their radiation dose enhancement potential on PC3 cell lines.

PMID- 29593409
TI  - Effective heart disease prediction system using data mining techniques.
AB  - The health care industries collect huge amounts of data that contain some hidden
      information, which is useful for making effective decisions. For providing
      appropriate results and making effective decisions on data, some advanced data
      mining techniques are used. In this study, an effective heart disease prediction
      system (EHDPS) is developed using neural network for predicting the risk level of
      heart disease. The system uses 15 medical parameters such as age, sex, blood
      pressure, cholesterol, and obesity for prediction. The EHDPS predicts the
      likelihood of patients getting heart disease. It enables significant knowledge,
      eg, relationships between medical factors related to heart disease and patterns,
      to be established. We have employed the multilayer perceptron neural network with
      backpropagation as the training algorithm. The obtained results have illustrated
      that the designed diagnostic system can effectively predict the risk level of
      heart diseases.

PMID- 29593410
TI  - Nanosilica-supported liposome (protocells) as a drug vehicle for cancer therapy.
AB  - This study encompasses the development and comparison of nanosilica-supported
      liposome (protocells), conventional liposome, and polyethylene glycol (PEG)
      liposome. An effort was made to study the drug encapsulation efficiency and the
      in vitro release of the drug, and whether protocells (nanovesicles) could sustain
      the release of the drug by increasing the residence time, which could reduce the
      dose-related systemic toxicity of the drug, that is, vincristine sulfate.
      Nanovesicles had a good encapsulation efficiency (71%), which was comparable to
      the conventional and PEG-liposome, which were 74% and 78%, respectively. The
      obtained vesicles were in the size range 100-150 nm, and the drug release
      efficiency of conventional, PEGylated, and protocells liposome was about 67%,
      42%, and 52%, respectively, in 150 minutes. The intermediate value of nanosilica
      supported liposome indicates the ability for stable and controlled release of the
      drug, which prevents the rapid burst or slower release of the drug. This study
      reveals that protocells as nanovesicles could be a better choice for the delivery
      of cancer drugs such as vincristine sulfate.

PMID- 29593411
TI  - Imaging of extracellular vesicles derived from human bone marrow mesenchymal stem
      cells using fluorescent and magnetic labels.
AB  - Background: Mesenchymal stem cells have been shown therapeutic in various
      neurological disorders. Recent studies support the notion that the predominant
      mechanism by which MSCs act is through the release of extracellular vesicles
      (EVs). EVs seem to have similar therapeutic activity as their cellular
      counterparts and may represent an interesting alternative standalone therapy for
      various diseases. The aim of the study was to optimize the method of EV imaging
      to better understand therapeutic effects mediated by EVs. Methods: The
      fluorescent lipophilic stain PKH26 and superparamagnetic iron oxide nanoparticles
      conjugated with rhodamine (Molday ION Rhodamine BTM) were used for the labeling
      of vesicles in human bone marrow MSCs (hBM-MSCs). The entire cycle from
      intracellular vesicles to EVs followed by their uptake by hBM-MSCs has been
      studied. The identity of vesicles has been proven by antibodies against: anti
      CD9, -CD63, and -CD81 (tetraspanins). NanoSight particle tracking analysis (NTA),
      high-resolution flow cytometric analysis, transmission electron microscopy (TEM),
      ELYRA PS.1 super-resolution microscopy, and magnetic resonance imaging (MRI) were
      used for the characterization of vesicles. Results: The PKH26 and Molday ION were
      exclusively localized in intracellular vesicles positively stained for EV
      markers: CD9, CD63, and CD81. The isolated EVs represent heterogeneous population
      of various sizes as confirmed by NTA. The TEM and MRI were capable to show
      successful labeling of EVs using ION. Co-culture of EVs with hBM-MSCs revealed
      their uptake by cells in vitro, as visualized by the co-localization of PKH26 or
      Molday ION with tetraspanins inside hBM-MSCs. Conclusion: PKH26 and Molday ION
      seem to be biocompatible with EVs, and the labeling did not interfere with the
      capability of EVs to re-enter hBM-MSCs during co-culture in vitro. Magnetic
      properties of IONs provide an additional advantage for the imaging of EV using
      TEM and MRI.

PMID- 29593412
TI  - Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects
      of loading methods on bone marrow stromal cell differentiation in vivo and in
      vitro.
AB  - Background: Surface modification of titanium dioxide (TiO2) implants promotes
      bone formation and shortens the osseointegration period. Kaempferol is a
      flavonoid that has the capacity to promote osteogenic differentiation in bone
      marrow stromal cells. The aim of this study was to promote bone formation around
      kaempferol immobilized on TiO2 implants. Methods: There were four experimental
      groups. Alkali-treated TiO2 samples (implants and discs) were used as a control
      and immersed in Dulbecco's phosphate-buffered saline (DPBS) (Al-Ti). For the
      coprecipitation sample (Al-cK), the control samples were immersed in DPBS
      containing 50 ug kaempferol/100% ethanol. For the adsorption sample (Al-aK), 50
      ug kaempferol/100% ethanol was dropped onto control samples. The surface
      topography of the TiO2 implants was observed by scanning electron microscopy with
      energy-dispersive X-ray spectroscopy, and a release assay was performed. For in
      vitro experiments, rat bone marrow stromal cells (rBMSCs) were cultured on each
      of the TiO2 samples to analyze cell proliferation, alkaline phosphatase activity,
      calcium deposition, and osteogenic differentiation. For in vivo experiments, TiO2
      implants placed on rat femur bones were analyzed for bone-implant contact by
      histological methods. Results: Kaempferol was detected on the surface of Al-cK
      and Al-aK. The results of the in vitro study showed that rBMSCs cultured on Al-cK
      and Al-aK promoted alkaline phosphatase activity, calcium deposition, and
      osteogenic differentiation. The in vivo histological analysis revealed that Al-cK
      and Al-aK stimulated new bone formation around implants. Conclusion: TiO2 implant
      immobilized kaempferol may be an effective tool for bone regeneration around
      dental implants.

PMID- 29593413
TI  - Serum levels of beta-hydroxybutyrate and pyruvate, metabolic changes and
      cognitive function in patients with schizophrenia during antipsychotic treatment:
      a preliminary study.
AB  - Background: beta-hydroxybutyrate (beta-HB) and pyruvate have been associated with
      the brain energy utilization, which may play a role in the pathophysiology of
      schizophrenia. In this prospective study, we aim to investigate the trends of
      beta-HB and pyruvate levels, metabolic changes, and cognitive function in
      schizophrenia patients receiving antipsychotic treatment. Objective: We recruited
      38 schizophrenia patients who had been treated with antipsychotics for 12 weeks,
      as well as 38 healthy age- and gender-matched subjects. Blood samples were taken
      from the patients at baseline and week 12 to determine the serum levels of beta
      HB, pyruvate, and metabolic parameters, while blood samples of the healthy
      controls were taken at baseline. We evaluated the psychopathology using the
      Positive and Negative Syndrome Scale and cognitive function using the Brief
      Assessment of Cognition in Schizophrenia. Results: During the 12-week follow-up
      period, the beta-HB levels in patients with schizophrenia showed a decreasing
      trend, particularly in those undergoing treatment with aripiprazole or
      ziprasidone. The serum levels of beta-HB in patients at baseline and week 12 were
      both higher than the levels in the healthy controls. Among the schizophrenia
      patients, changes in beta-HB were positively correlated with changes in executive
      function. On the other hand, serum pyruvate levels remained steady during the 12
      week follow-up period, and we found no significant correlation between pyruvate
      changes and changes in cognitive function or clinical symptoms. Conclusion: Our
      findings indicate that beta-HB may possess a potential indicator of energy
      utilization and have a protective role in executive function in patients with
      schizophrenia. Additional longitudinal studies with a larger sample size and
      longer follow-up periods are necessary to identify the relationship of metabolite
      regulation and cognitive function during schizophrenia patients' exposure to
      antipsychotics.

PMID- 29593414
TI  - A low dose of risperidone resolved Charles Bonnet syndrome after an unsuccessful
      trial of quetiapine: a case report.
AB  - Charles Bonnet syndrome (CBS) is a diagnosis of exclusion. Typical affected
      patients have impaired visual acuity, vivid recurring visual hallucinations, and
      no cognitive impairment. Vision loss is most commonly due to macular
      degeneration, although many other causes exist. Here, we report a case of an 87
      year-old woman with CBS and discuss the diagnosis and treatment.

PMID- 29593415
TI  - Exercise habituation is effective for improvement of periodontal disease status:
      a prospective intervention study.
AB  - Background and purpose: Periodontal disease is closely related to lifestyle
      related diseases and obesity. It is widely known that moderate exercise habits
      lead to improvement in lifestyle-related diseases and obesity. However, little
      research has been undertaken into how exercise habits affect periodontal disease.
      The purpose of this study was to examine the effect of exercise habits on
      periodontal diseases and metabolic pathology. Methods: We conducted a prospective
      intervention research for 12 weeks. The subjects were 71 obese men who
      participated in an exercise and/or dietary intervention program. Fifty subjects
      were assigned to exercise interventions (exercise intervention group) and 21
      subjects were assigned to dietary interventions (dietary intervention group).
      This research was conducted before and after each intervention program. Results:
      In the exercise intervention group, the number of teeth with a probing pocket
      depth (PPD) >=4 mm significantly decreased from 14.4% to 5.6% (P<0.001), and the
      number of teeth with bleeding on probing (BOP) significantly decreased from 39.8%
      to 14.4% (P<0.001). The copy counts of Tannerella forsythia and Treponema
      denticola decreased significantly (P=0.001). A positive correlation was found
      between the change in the copy count of T. denticola and the number of teeth with
      PPD >=4 mm (P=0.003) and the number of teeth with BOP (P=0.010). A positive
      correlation was also found between the change in the copy count of T. denticola
      and body weight (P=0.008), low-density lipoprotein cholesterol (P=0.049), and
      fasting insulin (P=0.041). However, in the dietary intervention group the copy
      count of T. denticola decreased significantly (P=0.007) and there was no
      correlation between the number of periodontal disease-causing bacteria and PPD
      and BOP. Conclusion: Our results are the first to show that exercise might
      contribute to improvements in periodontal disease.

PMID- 29593416
TI  - Influence of stroke volume variation on fluid treatment and postoperative
      complications in thoracic surgery.
AB  - Background: Fluid management in critically ill patients usually relies on
      increasing preload to augment cardiac output. In the present study, we aimed to
      evaluate whether stroke volume variation (SVV) can guide fluid therapy and reduce
      complications. Patients and methods: In this retrospective study, a total of 88
      patients who underwent lobectomy were divided into two groups: group 1 (SVV,
      n=43) and group 2 (conventional or central venous pressure [CVP], n=45). Heart
      rate, blood pressure, oxygen saturation, SVV (only group 1), CVP (all patients),
      urea, creatinine, and hemoglobin levels before and after surgery, use of fluid,
      blood and inotropic agents, and postoperative complications were recorded
      retrospectively. Results: The mean age of the study population was 56.9+/-14.4
      years and 75% of the patients were male. SVV was used in fluid therapy in 48.9%
      of the patients. The use of SVV resulted in an increased use of crystalloids and
      colloids with increased urine output per hour (p<0.05). Of patients in the SVV
      group and the CVP group, 44.1% and 51.1% developed at least one complication,
      respectively (p=0.531). The rate of respiratory complications including
      atelectasis, pneumonia, hypoxemia, and an increased production of secretions was
      21% in the SVV group and 37.7% in the CVP group (p=0.104). The rate of
      complications and the length of hospital stay were comparable between the groups
      (p>0.05). Conclusion: Our study results showed that the use of SVV increased the
      use of crystalloids and colloids and favorably affected urine output per hour but
      did not reduce complications in thoracic surgery.

PMID- 29593417
TI  - Long-term outcomes and predictors of survival after cardiopulmonary resuscitation
      for in-hospital cardiac arrest in a tertiary care hospital in Thailand.
AB  - Background: There are limited data available regarding long-term survival and its
      predictors in cases of in-hospital cardiac arrest (IHCA) in which patients
      receive cardiopulmonary resuscitation. Purpose: The objectives of this study were
      to determine the 1-year survival rates and predictors of survival after IHCA.
      Patients and methods: Data were retrospectively collected on all adult patients
      who were administered cardiopulmonary resuscitation from January 1, 2013 to
      December 31, 2014 in Srinagarind Hospital (Thailand). Clinical outcomes of
      interest and survival at discharge and 1 year after hospitalization were
      reviewed. Descriptive statistics and survival analysis were used to analyze the
      outcomes. Results: Of the 202 patients that were included, 48 (23.76%) were still
      alive at hospital discharge and 17 (about 8%) were still alive at 1 year post
      cardiac arrests. The 1-year survival rate for the cardiac arrest survivors post
      hospital discharge was 72.9%. Prearrest serum HCO3<20 meq/L, asystole, urine <800
      cc/d, postarrest coma, and absence of pupillary reflex were predictors of death.
      Conclusion: Only 7.9% of patients with IHCA were alive 1 year following cardiac
      arrest. Prearrest serum HCO3<20 meq/L, asystole, urine <800 cc/d, postarrest
      coma, and absence of pupillary reflex were the independent factors that predicted
      long-term mortality.

PMID- 29593418
TI  - miR-622 suppresses tumor formation by directly targeting VEGFA in papillary
      thyroid carcinoma.
AB  - Background: MicroRNAs (miRNAs) were reportedly to play crucial roles in papillary
      thyroid carcinoma (PTC) tumorigenesis and development. Therefore, the discovery
      of miRNAs may provide a new and powerful tool for diagnosis and treatment of PTC.
      Purpose: The aim of this study was to investigate the biological function and
      underlying mechanism of miR-622 in PTC. Materials and methods: The expression
      levels of miR-622 in PTC patient tissues and cell lines were determined by
      quantitative RT-PCR (qRT-PCR). The biological function including cell
      proliferation, colony formation, migration and invasion, as well as underling
      mechanism of miR-622 in PTC, were also evaluated by a series of in vitro and in
      vivo experiments. Results: miR-622 expression level was significantly
      downregulated in PTC tissues and cell lines. Decreased miR-622 expression was
      associated with advanced clinical stage and lymph node metastasis (P<0.01). The
      overexpression of miR-622 in TPC-1 cells inhibited cell proliferation, migration
      and invasion in vitro, as well as suppress tumor growth in vivo. Moreover, we
      also demonstrated that miR-622 specifically targeted the 3'-UTR regions of
      vascular endothelial growth factor A (VEGFA) and inhibited its expression both
      mRNA level and protein levels. Overexpression of VEGFA reversed miR-622-mediated
      inhibition effect on cell proliferation, migration and invasion in thyroid cancer
      cells. More importantly, VEGFA expression was significantly increased and
      inversely correlated with the levels of miR-622 in PTC tissues. Conclusion: These
      results show that miR-622 acts as a tumor suppressor in thyroid cancer, at least
      in part, via targeting VEGFA, and suggest that miR-622 may serves as a potential
      target for treatment of thyroid cancer patients.

PMID- 29593420
TI  - Novel long noncoding RNA GACAT3 promotes colorectal cancer cell proliferation,
      invasion, and migration through miR-149.
AB  - Aim: To explore the expression and clinical significance of long noncoding RNA
      (lncRNA) gastric cancer-associated transcript 3 (GACAT3) in human colorectal
      cancer (CRC). Methods: Expression of GACAT3 in CRC tissues and cell lines was
      measured using quantitative real-time PCR. CCK-8 and colony formation assays were
      used to assess the effect of GACAT3 on CRC cell line proliferation. Transwell
      invasion and migration assays were performed to detect the effect of GACAT3 on
      CRC cell line invasion and migration. Bioinformatics prediction, luciferase
      reporter assay, and pull-down assay were used to determine if miR-149 was a
      target of GACAT3. In addition, we also conducted colony formation assays and
      invasion assays to verify that GACAT3 promotes tumor progression through miR-149.
      Finally, in vivo tumorigenesis studies were used to demonstrate subcutaneous
      tumor growth. Results: In the present study, we found that GACAT3 was highly
      expressed in CRC tissues and cell lines. Si-GACAT3 significantly decreased cell
      proliferation, motility, and invasiveness both in vitro and in vivo. We confirmed
      that downregulated GACAT3 significantly increased the expression of miR-149, and
      miR-149 binds to GACAT3 in a sequence-specific manner using luciferase reporter
      assays and pull-down assay. Further functional experiments indicated that GACAT3
      could directly upregulate SP1 and STAT3 expressions by functioning as a competing
      endogenous RNA for miR-149, and consequentially, promoting CRC cell proliferation
      and invasion in vitro. Conclusion: This study demonstrated that GACAT3 promotes
      tumor progression through competitive binding to miR-149 and suggests a promising
      new strategy for anti-CRC therapy.

PMID- 29593419
TI  - Functional miRNAs in breast cancer drug resistance.
AB  - Owing to improved early surveillance and advanced therapy strategies, the current
      death rate due to breast cancer has decreased; nevertheless, drug resistance and
      relapse remain obstacles on the path to successful systematic treatment. Multiple
      mechanisms responsible for drug resistance have been elucidated, and miRNAs seem
      to play a major part in almost every aspect of cancer progression, including
      tumorigenesis, metastasis, and drug resistance. In recent years, exosomes have
      emerged as novel modes of intercellular signaling vehicles, initiating cell-cell
      communication through their fusion with target cell membranes, delivering
      functional molecules including miRNAs and proteins. This review particularly
      focuses on enumerating functional miRNAs involved in breast cancer drug
      resistance as well as their targets and related mechanisms. Subsequently, we
      discuss the prospects and challenges of miRNA function in drug resistance and
      highlight valuable approaches for the investigation of the role of exosomal
      miRNAs in breast cancer progression and drug resistance.

PMID- 29593421
TI  - Forecast of actin-binding proteins as the oncotarget in osteosarcoma - a review
      of mechanism, diagnosis and therapy.
AB  - Osteosarcoma (OS) is the most common bone malignant tumor with a high rate of
      lung metastasis and principally emerges in children and adolescents. Although
      neoadjuvant chemotherapy is widely used around the world, a high rate of
      chemoresistance occurs and frequently generates a poor prognosis. Therefore,
      finding a new appropriate prognostic marker for OS is a valuable research
      direction, which will give patients a better chance to receive proper therapy.
      Actin-binding proteins (ABPs) are a group of proteins that interact with actin
      cytoskeleton and play a crucial role in the regulation of the cell motility and
      morphology in eukaryotes. Meanwhile, ABPs also act as a bridge between the
      cytomembrane and nucleus, which transmit the outside-in and inside-out signals in
      cytoplasm. Furthermore, ABPs alter the dynamic structure of actin and regulate
      the invasion and metastasis of cancer. Hence, ABPs have a wide application in
      predicting the prognosis, and may be new targets, in tumor therapy. This review
      focuses on a series of ABPs and discusses their modulatory functions. It provides
      a new insight into the classification of ABPs' functions in the process of
      invasion and metastasis in OS and illuminates the potential ability in predicting
      the prognosis of OS patients.

PMID- 29593422
TI  - Overexpression of HHLA2, a member of the B7 family, is associated with worse
      survival in human colorectal carcinoma.
AB  - Background: Colorectal carcinoma (CRC) is one of the most common malignancies,
      and immunotherapy has opened a new field of cancer treatment in recent years.
      Generally, CRC does not benefit from immunotherapy. HHLA2, a member of the B7
      family, is a novel immune checkpoint molecule, and the prognostic value of HHLA2
      in CRC patients and the association between HHLA2 expression and
      clinicopathological characteristics remains unknown. Materials and methods: This
      study included 63 patients diagnosed with CRC, and their resected specimens were
      obtained and constructed as a tissue microarray. Expression of HHLA2 and CD8 was
      detected by the double immunohistochemistry method. Based on follow-up data,
      correlations of HHLA2 expression and clinicopathological features, including
      overall survival, in CRC patients were evaluated. Results: High HHLA2 expression
      was detected in CRC tumor tissues, compared to the adjacent noncancerous tissues.
      HHLA2 expression level was significantly related to the depth of invasion
      (P=0.044) and CD8+ T-cell infiltration status (P=0.016), and predicted high
      mortality rate (P=0.035). HHLA2 acted as an independent predictive factor in the
      overall survival of CRC patients (P=0.039, hazard ratio=2.162, 95% CI 1.041
      3.084). Conclusion: HHLA2 expression is upregulated in CRC patients, and HHLA2 is
      an independent prognostic factor of overall survival of CRC patients. High HHLA2
      expression is closely correlated with CD8 T-cell infiltration status and can
      predict poor prognosis in CRC patients.

PMID- 29593423
TI  - High expression of COL10A1 is associated with poor prognosis in colorectal
      cancer.
AB  - Background: High expression of collagen type X alpha 1 chain (COL10A1), a member
      of the collagen family, had been observed in various human cancers, but the
      detailed function and molecular mechanism of COL10A1 were largely unclear. Aim:
      The aim of this study was to investigate the expression of COL10A1 in colorectal
      cancer (CRC) tissues and cells and to reveal its biological function and
      mechanism in CRC. Materials and methods: Immunohistochemistry (IHC), real-time
      quantitative polymerase chain reaction (QPCR) and Western blot experiments were
      used to determine the clinical relevance between expression levels of COL10A1 and
      CRC. Results: Compared with normal tissues, COL10A1 expression was significantly
      higher in CRC tissues. Biological functional experiments showed that
      overexpression of COL10A1 enhanced proliferation, migration, and invasion of CRC
      cells, and knockdown of COL10A1 inhibited tumorigenesis in vivo. Western blot
      assays showed that COL10A1 promoted the process of epithelial-mesenchymal
      transition (EMT). The overexpression of COL10A1 was associated with adverse
      prognosis in CRC by tissue microarray (TMA) analysis. Conclusion: Our findings
      had provided evidences to support the fact that COL10A1 was abnormally up
      expressed in CRC and involved in the progression of CRC and the process of EMT.
      Furthermore, we demonstrated that the high-level expression of COL10A1 was an
      independent risk factor of prognosis and overall survival in CRC patients. These
      suggested that COL10A1 might be a new potential target for cancer therapy in the
      future.

PMID- 29593424
TI  - Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via
      induction of PUMA-mediated apoptosis.
AB  - Background: Glioblastoma is one of the most aggressive and common malignancies of
      the central nervous system in humans. Owing to the correlation of high Hsp90
      expression with prognosis and clinical pathology features of diverse types of
      cancer, targeting Hsp90 with small-molecule inhibitors has become a promising
      anticancer strategy. Purpose: In this study, we aimed to explore the possibility
      of anticancer effect of NMS-E973 in giloblastoma and elucidate the mechanism.
      Methods: Cell based MTT assay and colony formation assay were used to detect cell
      viability. Apoptosis was analyzed by nuclear staining with Hoechst 33258 and
      Annexin V/propidium iodide staining followed by flow cytometry. Western-blot and
      RT-PCR were used to detect gene expression. Xenograft assay was used to explore
      the anticancer effect of NMS-E973 in vivo. Results: We found that NMS-E973
      induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture
      and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS
      E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing
      apoptosis in glioblastoma cells. Furthermore, PUMA was induced by NMS-E973
      treatment in xenograft tumors, and deficiency in PUMA significantly suppressed
      the antitumor effects of NMS-E973. Conclusion: Our study suggests that PUMA
      mediated apoptosis is important for the therapeutic responses of NMS-E973.
      Induction of PUMA might be a potential biomarker for predicting NMS-E973
      responses.

PMID- 29593425
TI  - Lung squamous cell carcinoma associated with hypoparathyroidism with
      sensorineural deafness and renal dysplasia syndrome: a case report.
AB  - Hypoparathyroidism with sensorineural deafness and renal dysplasia (HDR) syndrome
      is an autosomal dominant condition caused by mutations of the gene encoding the
      dual zinc-finger transcription factor, GATA3. A previous study identified some
      patients with GATA3 gene variants and breast cancer, suggesting that GATA3
      variants may contribute to tumorigenesis in estrogen receptor 1-positive breast
      tumors; however, these patients did not have HDR syndrome. A 32-year-old
      nonsmoking Japanese woman was histologically diagnosed with lung squamous cell
      carcinoma associated with HDR syndrome and a c.C952T>C (p.C318R) germline
      mutation in GATA3. This is the first report describing cancer in a patient with
      HDR syndrome. Our data indicates that GATA3 mutations may be a potential
      therapeutic target for lung cancer.

PMID- 29593426
TI  - Clinical and economic impact of the 21-gene recurrence score assay in adjuvant
      therapy decision making in patients with early-stage breast cancer: pooled
      analysis in 4 Basque Country university hospitals.
AB  - Purpose: The 21-gene recurrence score (RS) is a genomic test developed as a
      prognostic and predictive tool to improve the treatment decision making in cases
      of estrogen receptor-positive and human epidermal growth factor receptor 2
      negative early-stage breast cancer. This study examined the clinical and economic
      impact of its use in 4 Basque Country university hospitals. Methods: Taking into
      consideration the RS result, we recorded the recommended initial systemic
      adjuvant therapy (endocrine therapy with or without chemotherapy) according to
      standard clinicopathologic factors and the final decision about chemotherapy.
      Then, if the RS was high, chemotherapy was recommended; it was not recommended if
      the RS was low; for those with an intermediate RS, clinicopathologic factors were
      considered, and the initial recommendation based on those factors was maintained.
      In addition, the probability of switching treatment was calculated. Then, we
      developed an economic evaluation by measuring the treatment's incremental short
      term budget impact from both the societal perspective and that of the Basque
      Health System. Patients' characteristics and chemotherapy use were analyzed using
      logistic regressions and receiver operating characteristic curves. Results:
      Without an RS, chemotherapy would have been prescribed to 56% of 401 patients,
      but, with RS use, that percentage decreased to 25. The overall rate of decision
      change was 35.4%. Test inclusion led to a reduction in chemotherapy costs of ?922
      per patient in the total population. Although this reduction did not entirely
      offset the cost of the test, the productivity loss per patient was reduced by
      ?1,977. Conclusion: The 21-gene RS test significantly changed the indication for
      chemotherapy. As chemotherapy treatments with no benefit were avoided, patients'
      quality of life was improved. The short-term economic impact was negative for the
      Basque Health Service, but savings resulted when sick-leave costs were included.

PMID- 29593428
TI  - Can patient safety be improved by reducing the volume of "inappropriate
      prescribing tasks" handed over to out-of-hours junior doctors?
AB  - Background: First-year doctors found that during out-of-hours shifts they were
      being delayed and distracted from reviewing potentially sick/deteriorating
      patients by a high volume of prescribing tasks. This predominately consisted of
      oral anticoagulation prescribing and rewrites of drug charts. We hoped that if we
      could reduce this burden of "inappropriate prescribing tasks", we could not only
      improve junior doctors' job satisfaction and opportunities for training but also
      give them more time for patient reviews. Methods: Three weekends were initially
      audited to quantify the number of "inappropriate prescribing tasks" using data
      from the hospital's computerized task assigning system. On three subsequent
      weekends, a checklist was handed out to the ward teams on Friday mornings. This
      checklist was designed to encourage the day teams to check that drug charts would
      not need oral anticoagulation or rewriting over the weekend. Results: An overall
      reduction in "inappropriate prescribing tasks" of 46% with a specific reduction
      in inappropriate oral anticoagulation prescribing of 65% was observed.
      Inappropriate drug chart rewrites were reduced by 30%. The reduction in the mean
      number of pre-intervention inappropriate prescribing tasks (as a percentage of
      total prescribing tasks) and the post-intervention mean was 6.94% (95% confidence
      interval -0.54 to 14.42, p-value=0.062). Conclusion: Improved job satisfaction
      and a perceived reduced workload were noted from post-intervention qualitative
      surveys. While improved patient safety directly resulting from this intervention
      is more difficult to establish, and the observed reduction in inappropriate
      prescribing was only approaching statistical significance, our colleagues
      commented in post-intervention feedback that they felt they had more time, and
      felt less pressured, while attending patients. The workload of junior doctors can
      exert a significant effect on patient care, and simple measures can alleviate
      this burden. Furthermore, computerized hospital task management systems are an
      underutilized source of data for audit and quality improvement.

PMID- 29593427
TI  - Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth
      muscle cells through the cyclic adenosine monophosphate/nuclear factor-kappaB
      pathway in vitro.
AB  - Background: Intestinal smooth muscle cells (SMCs) undergo substantial
      morphological, phenotypic, and contractile changes during inflammatory bowel
      disease (IBD). SMCs act as a source and target for different inflammatory
      mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon
      like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti
      inflammatory effects in different tissues including the gastrointestinal tract
      through various mechanisms. Aim: The aim of this research is to explore the
      effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory
      markers from mouse colon smooth muscle cells (CSMCs) after stimulation with
      lipopolysaccharide (LPS). Materials and methods: Freshly isolated CSMCs from male
      BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 MUg/mL),
      LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of
      inflammatory cytokines was then evaluated by antibody array membrane. Results:
      CSMCs showed basal expression of several cytokines which was enhanced with the
      induction of inflammation by LPS. However, exendin-4 (50 and 100 nM)
      significantly (p<0.05) reduced the expression of multiple cytokines including
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), T cell
      activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage
      colony stimulating factor (M-CSF). To confirm these results, expression of these
      cytokines was further assessed by enzyme-linked immunosorbent assay and real-time
      polymerase chain reaction and similar results were also observed. Moreover,
      secretion of TNF-alpha and IL1-alpha into the conditioned media was significantly
      downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS
      increased NF-kappaB phosphorylation, while exendin-4 significantly reduced levels
      of NF-kappaB phosphorylation. Conclusion: These data indicate that GLP-1 analogs
      can exert significant anti-inflammatory effects on CSMCs and can potentially be
      used as an adjunct treatment for inflammatory bowel conditions.

PMID- 29593429
TI  - Upregulation of Arp2 expression is associated with the prognosis and prediction
      of lymph node metastasis in bladder urothelial carcinoma.
AB  - Objective: Upregulation of actin-related protein 2/3 complex subunit 2 (Arp2) is
      observed in various tumors, but its expression pattern has not been revealed in
      bladder urothelial carcinoma (BUC). The purpose of this study was to investigate
      the role of Arp2 expression in the pathological features and the prognosis as
      well as lymph node metastasis of BUC. Methods: A total of 228 tissue specimens
      from BUC patients who underwent a radical cystectomy were collected. In addition,
      40 lymph node specimens and 40 normal bladder tissue specimens as controls were
      used. All of the specimens were used to construct a tissue microarray and were
      subsequently subjected to immunohistochemical staining for Arp2 expression.
      Logistic and Cox regression analyses and Kaplan-Meier curve analysis were applied
      to analyze the relation between Arp2 expression and multiple clinical features of
      patients with BUC. Results: Immunohistochemical staining observation showed that
      Arp2 was mainly expressed in the cytoplasm and nucleus of positive cells and that
      Arp2 expression in BUC was significantly higher than that in normal bladder
      tissues. Arp2 expression in BUC tissues was associated with tumor size, tumor
      multiplicity, tumor stage, tumor grade, and lymph node metastasis (P < 0.05).
      Logistic regression analysis demonstrated that Arp2 expression was an independent
      risk factor for lymph node metastasis of BUC (P < 0.05). Kaplan-Meier curve
      analysis showed that increased Arp2 expression was associated with a shortened
      recurrence-free survival (RFS) and overall survival (OS) of BUC patients after
      radical cystectomy (P < 0.05). Conclusion: These findings suggest that Arp2 is
      significantly upregulated in BUC tissues when compared with normal bladder
      tissues, and that Arp2 expression is an independent predictor for lymph node
      metastasis, RFS, and OS.

PMID- 29593430
TI  - Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated
      radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities
      and response assessment.
AB  - Aims and objectives: The past 2 decades witnessed the strengthening of evidence
      favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of
      locally advanced rectal cancer. The study aims to evaluate the response and acute
      toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in
      the treatment of rectal cancer. Predictive factors to achieve pathological
      complete response (pCR) were analyzed, as a secondary endpoint. Materials and
      methods: All consecutive patients who underwent IMRT as part of neoadjuvant CHRT
      in the treatment of rectal cancer between August 2014 and December 2016 at a
      tertiary cancer care center were accrued for the study. The cohort underwent CHRT
      with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with
      continuous infusion of 5 fluorouracil during the first and the last 4 days of
      CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT
      was noted. Results: Forty-three subjects were accrued for the study. Radiation
      dermatitis and diarrhea were the only observed grade >=3 acute toxicities.
      Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%.
      Univariate and multivariate logistic regression showed that carcinoembryonic
      antigen was the only independent predictive factor to achieve pCR. Conclusion:
      IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal
      cancer is well tolerated and gives comparable results with respect to earlier
      studies in terms of pathological response and SPR. Further randomized controlled
      studies are needed to firmly state that IMRT is superior to 3-dimensional
      conformal radiotherapy.

PMID- 29593431
TI  - Prognostic value of ductal carcinoma in situ component in invasive ductal
      carcinoma of the breast: a Surveillance, Epidemiology, and End Results database
      analysis.
AB  - Background: The prognostic implication of concomitant ductal carcinoma in situ
      (DCIS) in invasive ductal carcinoma (IDC) remains controversial. Our objective
      was to investigate whether concomitant DCIS affects survival outcomes in patients
      with IDC. Materials and methods: Patients with nonmetastatic breast cancer who
      underwent surgery in 2010-2014 were included from the Surveillance, Epidemiology,
      and End Results program. Statistical analyses were conducted using chi2 test,
      linear-by-linear association, one-way analysis of variance, Kaplan-Meier method,
      Cox proportional hazards regression model, and propensity score matching (PSM).
      Results: A total of 61,745 patients were identified, including 44,630 (72.3%),
      13,559 (22.0%), and 3,556 (5.7%) patients with no DCIS component reported (No
      DCIS), DCIS <25% (L-DCIS), and >=25% (H-DCIS), respectively. Patients with H-DCIS
      were more likely to be younger (p<0.001), have smaller tumors (p<0.001),
      good/moderate differentiation (p<0.001), human epidermal growth factor receptor 2
      positive disease (p<0.001), receive mastectomy (p<0.001), and not receive
      radiotherapy (p<0.001) and chemotherapy (p<0.001). The median follow-up was 27
      months, and the 2-year breast cancer-specific survival (BCSS) in patients with No
      DCIS, L-DCIS, and H-DCIS was 97.3%, 98.0%, and 98.5%, respectively (p<0.001).
      Before PSM, H-DCIS was an independent favorable prognostic factor for BCSS;
      patients with H-DCIS had better BCSS compared to patients with No-DCIS (hazard
      ratio [HR] 0.674, 95% CI: 0.528-0.861, p=0.002), while the BCSS between No-DCIS
      and L-DCIS was similar (HR 0.944, 95% CI: 0.840-1.061, p=0.334). However, this
      survival advantage disappeared after PSM; there was significantly different BCSS
      between patients with No-DCIS and H-DCIS (HR 0.923, 95% CI: 0.653-1.304,
      p=0.650). H-DCIS was not associated with BCSS as compared to No-DCIS in the
      breast-conserving surgery (p=0.295) and mastectomy (p=0.793) groups. Conclusion:
      In breast cancer, patients with H-DCIS have unique clinicopathologic features
      compared to patients with No-DCIS. Before PSM, H-DCIS was associated with
      favorable BCSS as compared to No-DCIS. However, the survival advantage
      disappeared after PSM.

PMID- 29593432
TI  - Downregulation of hsa_circ_0011946 suppresses the migration and invasion of the
      breast cancer cell line MCF-7 by targeting RFC3.
AB  - Introduction: Although some circRNAs have been found to regulate the progression
      of malignancies, their functions and coupled molecular mechanisms are still
      unclear. In our study, we sought to assess the underlying molecular mechanisms of
      circRNAs in breast cancer and therefore explored the differentially expressed
      circRNAs and co-expression networks, followed by in vitro experiments. Materials
      and methods: High-throughput RNA sequencing was performed to obtain an unbiased
      profile of circRNA expression. CircRNA-miRNA-mRNA co-expression networks were
      predicted, and sequence analyses were carried out. The MTT, transwell migration
      and invasion assay was conducted in Michigan Cancer Foundation-7 cells that had
      been transfected with si-circRNA and si-negative control (si-NC). Results: A
      total of 152 circRNAs were differentially expressed in breast cancer tissues,
      among which 85 were upregulated and 67 downregulated. Out of these,
      hsa_circ_0011946 was selected and the subsequent bioinformatics analysis
      predicted that hsa_circ_0011946 sponging miR-26a/b directly targeted replication
      factor C subunit 3 (RFC3) and that its knockdown could inhibit RFC3 mRNA and
      protein expression. Furthermore, hsa_circ_0011946 loss-of-function significantly
      suppressed the migration and invasion of Michigan Cancer Foundation-7 cells.
      Conclusion: Together, these results indicate that hsa_circ_0011946 and RFC3
      comprise a novel pathway involved in the progression of breast cancer.

PMID- 29593433
TI  - Mechanical ventilation promotes lung metastasis in experimental 4T1 breast cancer
      lung-metastasized models.
AB  - Background/purpose: The aim of this study was to test the hypothesis that
      mechanical ventilation (MV) during cancer surgery induces lung stroma/tissue
      milieu changes, creating a favorable microenvironment for postoperative lung
      metastatic tumor establishment. Materials and methods: In Protocol A, female
      BALB/c mice were divided into an MV group and a control (no MV) group, both of
      which were anesthetized and subjected to intravenous injection of green
      fluorescent protein (GFP)-labeled mouse mammary carcinoma cell line (4T1) cells.
      After 24 h, the lung tissue was removed and the number of GFP-labeled 4T1 cells
      was calculated. In Protocol B, the clinically relevant mouse model of spontaneous
      breast cancer lung metastasis was used with surgical resection of the primary
      tumor to investigate the MV event that dictates postoperative lung metastasis.
      Female BALB/c mice were inoculated in the mammary fat pad with 4T1 cells. After
      14-d growth, mice were anesthetized and divided into an MV group and a control
      (no MV) group during surgical procedures (mastectomy). Metastatic tumor burden
      was assessed two weeks after mastectomy by both macroscopic metastatic nodule
      count, hematoxylin-eosin histology, immunohistochemistry for the macrophage
      marker (CD68), and epithelial cell adhesion molecule (EpCAM). Results: MV was
      associated with a significant increase in the number of circulating breast tumor
      cells (GFP-labeled 4T1 cells) remaining in the microvasculature of the lung
      (P<0.01). Immunohistochemical results showed increased infiltration of CD68
      positive macrophages within injured lung parenchyma and metastatic tumor as well
      as increased expression of EpCAM in metastatic nodules. Postoperative metastases
      were more prevalent in the mechanically ventilated mice group compared to the non
      ventilated group (P<0.05). Conclusion: MV-induced lung metastasis occurs by
      attracting circulating tumor cells to the site of the lung injury and by
      accelerating the proliferation of preexisting micro-metastases in the lung. These
      observations indicate that the metastasis-enhancing effect of MV should be
      considered in general anesthesia during cancer surgery.

PMID- 29593434
TI  - Lifestyle in pregnancy and cryptorchidism in sons: a study within two large
      Danish birth cohorts.
AB  - Purpose: Cryptorchidism is the most frequent congenital malformation in boys and
      is associated with low sperm count, infertility and testicular cancer. Unhealthy
      maternal lifestyle during pregnancy such as smoking, high prepregnancy body mass
      index (BMI) as well as alcohol and caffeine intake may constitute possible risk
      factors for cryptorchidism, but results from the few previous studies are
      conflicting. We aimed to explore the association between maternal lifestyle
      factors and occurrence of cryptorchidism in sons. Patients and methods: The
      Danish National Birth Cohort and the Aarhus Birth Cohort provided information on
      maternal lifestyle from early pregnancy. Data were linked to several Danish
      health registers, multiple imputation was used to handle missing data and Cox
      proportional hazards models were used to adjust for potential confounders.
      Results: In total, 85,923 boys were included, and of them, 2.2% were diagnosed
      with cryptorchidism. We observed the strongest associations between maternal
      tobacco smoking and prepregnancy BMI and cryptorchidism. Sons of women who smoked
      10-14 cigarettes/day had the highest hazard ratio (HR) for cryptorchidism (1.37;
      95% CI: 1.06-1.76), and for maternal BMI >=30 kg/m2, the HR was 1.32 (95% CI:
      1.06-1.65). Binge drinking was associated with an HR <1, if the women had one or
      two episodes in pregnancy (HR: 0.81; 95% CI: 0.67-0.98). Average maternal alcohol
      intake and caffeine intake during pregnancy were not significantly associated
      with a higher occurrence of cryptorchidism detected at birth or later in life.
      Conclusion: Maternal tobacco smoking, overweight and obesity in pregnancy were
      associated with higher occurrence of cryptorchidism in boys in this study.

PMID- 29593435
TI  - Mode of delivery is not associated with celiac disease.
AB  - Purpose: The purpose of this study was to investigate the association between
      mode of delivery and the risk of celiac disease in two large population-based
      birth cohorts with different prevalence of diagnosed celiac disease. Patients and
      methods: This is an observational register-based cohort study using two
      independent population cohorts. We used data from administrative registers and
      health administrative registers from Denmark and Norway and linked the data at
      the individual level. We included all children who were born in Denmark from
      January 1, 1995 to December 31, 2010 and all children who were born in Norway
      from January 1, 2004 to December 31, 2012. Results: We included 1,051,028
      children from Denmark. Cesarean sections were registered for 196,512 children
      (18.9%). Diagnosed celiac disease was registered for 1,395 children (0.13%). We
      included 537,457 children from Norway. Cesarean sections were registered for
      90,128 children (16.8%). Diagnosed celiac disease was registered for 1,919
      children (0.35%). We found no association between the mode of delivery and the
      risk of diagnosed celiac disease. The adjusted odds ratio for celiac disease for
      children delivered by any type of cesarean section compared to vaginal delivery
      was 1.11 (95% CI: 0.96-1.29) in the Danish cohort and 0.96 (95% CI: 0.84-1.09) in
      the Norwegian cohort. The adjusted odds ratio for celiac disease for children
      delivered by elective cesarean section compared to vaginal delivery was 1.20 (95%
      CI: 1.00-1.43) in the Danish cohort and 0.96 (95% CI: 0.79-1.17) in the Norwegian
      cohort. Conclusion: In this large registry-based study, mode of delivery was not
      associated with an increased risk of diagnosed celiac disease.

PMID- 29593436
TI  - Comparing methods to combine functional loss and mortality in clinical trials for
      amyotrophic lateral sclerosis.
AB  - Objective: Amyotrophic lateral sclerosis (ALS) clinical trials based on single
      end points only partially capture the full treatment effect when both function
      and mortality are affected, and may falsely dismiss efficacious drugs as futile.
      We aimed to investigate the statistical properties of several strategies for the
      simultaneous analysis of function and mortality in ALS clinical trials. Methods:
      Based on the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database,
      we simulated longitudinal patterns of functional decline, defined by the revised
      amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and conditional
      survival time. Different treatment scenarios with varying effect sizes were
      simulated with follow-up ranging from 12 to 18 months. We considered the
      following analytical strategies: 1) Cox model; 2) linear mixed effects (LME)
      model; 3) omnibus test based on Cox and LME models; 4) composite time-to-6-point
      decrease or death; 5) combined assessment of function and survival (CAFS); and 6)
      test based on joint modeling framework. For each analytical strategy, we
      calculated the empirical power and sample size. Results: Both Cox and LME models
      have increased false-negative rates when treatment exclusively affects either
      function or survival. The joint model has superior power compared to other
      strategies. The composite end point increases false-negative rates among all
      treatment scenarios. To detect a 15% reduction in ALSFRS-R decline and 34%
      decline in hazard with 80% power after 18 months, the Cox model requires 524
      patients, the LME model 794 patients, the omnibus test 526 patients, the
      composite end point 1,274 patients, the CAFS 576 patients and the joint model 464
      patients. Conclusion: Joint models have superior statistical power to analyze
      simultaneous effects on survival and function and may circumvent pitfalls
      encountered by other end points. Optimizing trial end points is essential, as
      selecting suboptimal outcomes may disguise important treatment clues.

PMID- 29593437
TI  - Calculating reading ease score of patient package inserts in Iran.
AB  - Background: The patient package inserts (PPIs), which contain the necessary
      information about medications intended for patients, need to be expressed in a
      clear language comprehensible to everyone. Objective: This study aimed to
      evaluate the readability and understandability of the drug package inserts for
      the inexpert people. Methods: The readability of the 158 PPIs of the 33 drugs,
      registered and manufactured in Iran, was calculated. The main criterion for
      selecting PPIs to include in this study was of those top-selling drugs during the
      year 2015 according to the Social Security Organization in Iran. The PPIs were
      collected from the pharmacies of the three major cities, namely, Tabriz, Ardabil
      and Meshgin Shahr. Then, using the Flesch-Dayani readability (FDR) tool adjusted
      for the Persian language, the average number of the words and syllables was
      counted to calculate and grade the readability score of the selected PPIs.
      Results: This study showed that the average FDR readability score for all the 33
      drugs is 52.52, which are graded 10th-11th. Of the PPIs, 70.89% were difficult to
      read, and on average, the readability of the PPIs was five times difficult than
      the standard ones. Only 13.92% PPIs were suitable for the 5th-7th grade, and
      15.19% of the package inserts ranked in the 8th-9th reading grade. Conclusion: A
      considerable number of the PPIs in Iran have low readability level and were not
      suitable for the inexpert readers. Since the treatment cost is very high, people
      tend to use medications arbitrarily or simply use old prescriptions. This study
      suggests the necessity of a major improvement in the readability level of the
      PPIs in order to ensure the usefulness of the PPIs to the majority of the
      consumers.

PMID- 29593439
TI  - Student, Faculty, and Staff Approval of University Smoke/Tobacco-Free Policies:
      An Analysis of Campus Newspaper Articles.
AB  - Objective: To provide a nontraditional source of data to university policymakers
      regarding student, faculty, and staff approval of university smoke/tobacco-free
      policies, as published through campus newspaper articles. Methods: From January
      to April 2016, a total of 2523 articles were retrieved concerning campus
      smoking/tobacco at 4-year, public universities. Of these, 54 articles met the
      inclusion factors, which described 30 surveys about campus approval of tobacco
      free policies and 24 surveys about smoke-free policies. Results: In all, the
      surveys included more than 130 000 respondents. With the exception of 4 surveys,
      all reported that the most of the respondents approved a tobacco/smoke-free
      campus policy. Conclusions: Although the study had several limitations, the
      findings provide a synthesis from a nontraditional data source that is consistent
      with findings from the peer-reviewed literature, in which most of the students,
      faculty, and staff on university campuses approve of smoke/tobacco-free campus
      policies.

PMID- 29593438
TI  - Glenohumeral internal rotation deficit in throwing athletes: current
      perspectives.
AB  - Glenohumeral internal rotation deficit (GIRD) is an adaptive process in which the
      throwing shoulder experiences a loss of internal rotation (IR). GIRD has most
      commonly been defined by a loss of >20 degrees  of IR compared to the
      contralateral shoulder. Total rotational motion of the shoulder is the sum of
      internal and external rotation and may be more important than the absolute value
      of IR loss. Pathologic GIRD has been defined as a loss of IR combined with a loss
      of total rotational motion. The leading pathologic process in GIRD is posterior
      capsular and rotator-cuff tightness, due to the repetitive cocking that occurs
      with the overhead throwing motion. GIRD has been associated with numerous
      pathologic conditions, including posterior superior labral tears, partial
      articular-sided rotator-cuff tears, and superior labral anterior-to-posterior
      tears. The mainstay of treatment for patients with GIRD is posterior capsular
      stretching and strengthening to improve scapular mechanics. In patients who fail
      nonoperative therapy, shoulder arthroscopy can be performed. Arthroscopic surgery
      in the high-level throwing athlete should be to restore them to their functional
      baseline with the minimum amount of intervention possible.

PMID- 29593440
TI  - Graves Disease in Central Ghana: Clinical Characteristics and Associated Factors.
AB  - Background: Graves disease (GD) has increased in prevalence over the past decade
      in Africa. Despite this, the condition is not well described, especially in sub
      Saharan Africa. Objective: We have described the clinical characteristics and
      associated factors of GD in a cohort of patients attending a resource-limited
      setting tertiary hospital. Methods: Patients were examined thoroughly and
      systematically tested for the degree of clinical and biochemical thyroid status.
      Thyroid volume, characteristics, and blood flow were assessed at presentation
      using ultrasonography. Factors associated with an inability to achieve clinical
      and biochemical thyroid remission were evaluated using multiple logistic
      regression analysis. Results: Overall, 182 patients were studied, 152 (83.5%)
      were women with a female:male ratio of 5.1:1.0. The mean age at presentation was
      39.9 +/- 14.7 years with women significantly older than men. Thyroid-associated
      orbitopathy (TAO) was observed in 56% of the participants and pretibial myxoedema
      in 6%. About 84% of the participants were hyperthyroid at presentation, 9% were
      euthyroid, 4% were hypothyroid, and 3% had subclinical hyperthyroidism. Inability
      to achieve biochemical and clinical remission at 24 months was associated with
      increased thyroid volume (odds ratio [OR]: 2.35, 95% confidence interval [CI]:
      1.85-2.52, P < .001), presence of TAO (OR: 2.15, 95% CI: 2.12-2.33, P < .001),
      increased FT3/FT4 ratio (OR: 1.33, 95% CI: 1.24-2.56, P = .004), and missed
      clinic appointment (OR: 5.2, 95% CI: 4.55-7.89, P < .001). Conclusions: Graves
      disease among Ghanaians is associated with significant signs at presentation.
      Inability to achieve remission within the first 24 months is associated with
      increased thyroid volume, TAO, an increased FT3/FT4 ratio, as well as missed
      clinic appointment.

PMID- 29593441
TI  - Learning style preferences of dental students at a single institution in Riyadh,
      Saudi Arabia, evaluated using the VARK questionnaire.
AB  - Background: Students differ in their preferred methods of acquiring, processing,
      and recalling new information. The aim of this study was to investigate the
      learning style preferences of undergraduate dental students and examine the
      influence of gender, Grade Point Average (GPA), and academic year levels on these
      preferences. Methods: The Arabic version of the visual, aural, read/write, and
      kinesthetic (VARK) questionnaire was administered to 491 students from the first-
      to the fifth-year academic classes at the College of Dentistry, King Saud
      University. Descriptive statistics were used to characterize the learning styles
      of the students, and Chi-square test and Fisher's test were used to compare the
      learning preferences between genders and among academic years. Significance was
      set at a p-value of <0.05. Results: A total of 368 dental students completed the
      questionnaire. The multimodal learning style was preferred by 63.04% of the
      respondents, with the remaining 36% having a unimodal style preference. The aural
      (A) and the kinesthetic (K) styles were the most preferred unimodal styles. The
      most common style overall was the quadmodal (VARK) style with 23.64% having this
      preference. These differences did not reach statistical significance (p>0.05).
      Females were more likely to prefer a bimodal learning style over a unimodal style
      (relative risk =2.37). Students with a GPA of "C" were less likely to have a
      bimodal or a quadmodal style preference compared to students with a GPA of "A"
      (relative risk =0.34 and 0.36, respectively). Second-year students were less
      likely to prefer a bimodal over a unimodal style compared to first-year students
      (relative risk =0.34). Conclusion: The quadmodal VARK style is the preferred
      learning method chosen by dental students, followed by unimodal aural and
      kinesthetic styles. Gender was found to influence learning style preferences.
      Students with a "C" GPA tend to prefer unimodal learning style preferences. The
      VARK questionnaire is a relatively quick and simple tool to reveal the learning
      style preferences on an individual or a group level. Dental educators should
      adjust their delivery methods to approximate the learning preferences of their
      students. Dental students are encouraged to adapt a multimodal style of learning
      to improve their academic results.

PMID- 29593442
TI  - Combined thickness of the uterus and placenta and ultrasonographic examinations
      of uteroplacental tissues in normal pregnancy, placentitis, and abnormal
      parturitions in heavy draft horses.
AB  - The combined thickness of the uterus and placenta (CTUP) and ultrasonographic
      images of uteroplacental tissues were investigated in 35 pregnant heavy draft
      horses in Months 7-12 of pregnancy. The mares were divided into three groups:
      those pathologically diagnosed as placentitis (placentitis group, n=3); those who
      had abortion, premature birth, or fetal malformation (abnormal group, n=7); and
      those who had no abnormal findings (normal group, n=25). In the normal group,
      CTUP increased as pregnancy progressed from Months 7 (median, 7.08 mm; range,
      5.68-11.27) to 12 (13.31 mm; 7.44-16.31 mm) (P<0.05) and was higher than those
      reported previously in Thoroughbred, quarter, and American paint horses. Values
      of CTUP greater than the 75th percentile of the normal group from Months 7 (7.54
      mm) to 12 (15.19 mm) were detected in 100% of the placentitis group (3/3) and in
      86% of the abnormal group (6/7). Ultrasonographic images showing placental
      separation were obtained in 67% of the placentitis group (2/3), 29% of the
      abnormal group (2/7), and 20% of the normal group (5/25). Pathological placental
      edema and ultrasonographic images showing uteroplacental roughness or
      distinguishability were observed even in the normal group. These findings suggest
      that increased CTUP and placental separation would reflect placentitis and
      abnormal pregnancies and may help to detect them in heavy draft horses.

PMID- 29593443
TI  - Displacement of the large colon in a horse with enterolithiasis due to changed
      positions observed by computed tomography.
AB  - Computed tomography (CT) was performed for an 18-year-old female pony with
      enterolithiasis in the prone and supine positions. CT images from the prone
      position revealed displacement of the large dorsal colon, which contained an
      enterolith to the ventral side of the abdomen, and those from the supine position
      revealed displacement to the dorsal side. A high-density material suggestive of a
      metallic foreign body was also observed in the enterolith core. An enterolith
      (422 g, 104 mm) was surgically removed from the large dorsal colon. This caused
      no complications after surgery and increased the horse's weight. Changing
      positions during CT helps identify the exact location of enterolith and
      intestinal displacement due to enterolith weight, as well as size and number.

PMID- 29593444
TI  - Blood glucose is unlikely to be a prognostic biomarker in acute colitis with
      systemic inflammatory response syndrome in Thoroughbred racehorses.
AB  - Although hyperglycemia at admission with colic has been reported to have a poor
      prognosis, there is no report specifically about acute colitis with systemic
      inflammatory response syndrome (SIRS) in horses. In this study, we measured blood
      glucose (Glu), insulin (Ins), and cortisol (Cor) levels in 17 Thoroughbred
      racehorses diagnosed as having acute colitis with SIRS, and examined the
      relationship between time-dependent changes in Glu, Ins, and Cor and prognosis.
      Glu levels were high in 3 horses at admission, but thereafter no horses had
      persistently high Glu levels. There was no significant difference in Glu, Ins,
      and Cor levels within 72 hr between surviving and non-surviving horses. In
      conclusion, the Glu level is unlikely to be a useful prognostic biomarker in
      acute colitis with SIRS.

PMID- 29593445
TI  - Effect of selection for eventing on the MSTN gene in Brazilian sport horses.
AB  - Polymorphisms in MSTN have previously been associated with equine performance.
      Therefore, the aim of this study was to identify variants in MSTN intron 1 in 16
      Brazilian Sport Horses selected for competition in eventing and their possible
      effects of selection on performance. Among the nine variants identified, eight
      had already been reported in previous studies or genomic databases, although they
      showed differences in frequencies when compared with other horse breeds.
      Moreover, a new mutation was identified in two horses, both in heterozygous form.
      Considering the absence of molecular studies in this valuable Brazilian breed,
      these findings represent an important contribution to the characterization of its
      genetic profile and may possibly aid in further genotype-phenotype association
      studies.

PMID- 29593446
TI  - Characterization of isolates of Bordetella bronchiseptica from horses.
AB  - Bordetella bronchiseptica is a well-known Gram-negative bacterial pathogen
      causing a plethora of diseases in different animals. Although its infection has
      been reported from pigs and dogs in India, no report of B. bronchiseptica from
      horses is described. We report for the first time, isolation, identification and
      characterization of strains of B. bronchiseptica from respiratory infection in
      horses from different states in India. The antimicrobial susceptibility testing
      showed resistance to penicillins, ceftazidime, and chloramphanicol. The virulence
      capability of the strains was confirmed by sequencing genes such as adenylate
      cyclase toxin (cyaA), bordetella virulence gene (bvgA) and by PCR detection of
      flagellin gene (fla). We demonstrate the involvement of B. bronchiseptica strains
      in respiratory tract infection in horses in India.

PMID- 29593447
TI  - Reducing psychopathic violence: A review of the treatment literature.
AB  - Psychopathy reflects a pathological form of personality that predisposes
      individuals to risk for perpetration of chronic and severe violence across their
      lifespan. The violence attributable to psychopathic persons constitutes a
      substantial portion of the societal burden to the public health and criminal
      justice systems and thus necessitates significant attention by prevention
      experts. However, there is a relatively nascent literature that has examined
      psychopathic persons' response to treatment, especially considering violence as
      an outcome. Nevertheless, there have been repeated averments about the
      amenability (or lack thereof) of psychopathy to treatment. In the present paper,
      we attempt to provide a comprehensive review of studies assessing the relation of
      psychopathy to violence outcomes following intervention. Our review of studies
      suggests there is reason to suspect that specific and tailored interventions
      which take into consideration psychopathic persons' unique patterns of behavioral
      conditioning and predispositions may have the potential to reduce violence.
      However, equally important, certain interventions may potentially exacerbate
      these persons' violent behavior. The nature of the outcomes is likely highly
      dependent on the specific components of the intervention itself. We conclude that
      future research should increase methodological rigor by striving to include
      treatment control groups and increasing the transparency of the implemented
      interventions.

PMID- 29593449
TI  - Different Places, Different Stories: A Study of Spatial Heterogeneity of County
      Level Fertility in China.
AB  - Background: China has been characterized by persistently low fertility rates
      since the 1990s. Existing literature has examined the relationships of fertility
      levels with social, economic, and policy-related determinants. However, the
      possible spatial variations in these relationships have not been investigated.
      Objective: The purpose of this study is to examine the potential spatially
      varying relationships between county-level fertility rates and policy and
      socioeconomic factors in China. Methods: Using geocoded 2010 county-level census
      data, this study adopts the geographically weighted regression (GWR) method to
      identify place-specific relationships between county-level total fertility rate
      (TFR) and socioeconomics and policy-related factors. Conclusions: We find
      relationships between TFR and widely used social, economic, and policy-related
      factors (rural Hukou, ethnic minority, female education, net migration rate, poor
      living standard, sex ratio at birth, and fertility policy compliance ratio) vary
      spatially in terms of the direction, strength, and magnitude. The spatial
      variation is largely due to the difference in local characteristics. The
      differences and the complexities of localities cannot be told by a single story
      of either government intervention or socioeconomic development. Contribution:
      This study extends the existing fertility research in China by explicitly
      recognizing the spatial heterogeneity in the impacts of policy and socioeconomic
      factors on the local fertility rate. This study sets the stage for future
      research that will contextually analyze varying fertility rates at the sub
      national level in China and other countries.

PMID- 29593451
TI  - Editorial.

PMID- 29593448
TI  - Why psychopathy matters: Implications for public health and violence prevention.
AB  - Psychopathy is an early-appearing risk factor for severe and chronic violence.
      The violence largely attributable to psychopathy constitutes a substantial
      portion of the societal burden to the public health and criminal justice systems,
      and thus necessitates significant attention from prevention experts. Yet, despite
      a vast base of research in psychology and criminology, the public health approach
      to violence has generally neglected to consider this key variable. Fundamentally,
      the public health approach to violence prevention is focused on achieving change
      at the population level to provide the most benefit to the maximum number of
      people. Increasing attention to the individual-level factor of psychopathy in
      public health could improve our ability to reduce violence at the community and
      societal levels. We conclude that the research literature on psychopathy points
      to a pressing need for a broad-based public health approach with a focus on
      primary prevention. Further, we consider how measuring psychopathy in public
      health research may benefit violence prevention, and ultimately society, in
      general.

PMID- 29593450
TI  - flexsurv: A Platform for Parametric Survival Modeling in R.
AB  - flexsurv is an R package for fully-parametric modeling of survival data. Any
      parametric time-to-event distribution may be fitted if the user supplies a
      probability density or hazard function, and ideally also their cumulative
      versions. Standard survival distributions are built in, including the three and
      four-parameter generalized gamma and F distributions. Any parameter of any
      distribution can be modeled as a linear or log-linear function of covariates. The
      package also includes the spline model of Royston and Parmar (2002), in which
      both baseline survival and covariate effects can be arbitrarily flexible
      parametric functions of time. The main model-fitting function, flexsurvreg, uses
      the familiar syntax of survreg from the standard survival package (Therneau
      2016). Censoring or left-truncation are specified in 'Surv' objects. The models
      are fitted by maximizing the full log-likelihood, and estimates and confidence
      intervals for any function of the model parameters can be printed or plotted.
      flexsurv also provides functions for fitting and predicting from fully-parametric
      multi-state models, and connects with the mstate package (de Wreede, Fiocco, and
      Putter 2011). This article explains the methods and design principles of the
      package, giving several worked examples of its use.

PMID- 29593452
TI  - Assessment of Plasma S-Nitrosothiol Concentration by Electron Paramagnetic
      Resonance Spectrometry and Plasma Nitrotyrosine Levels by ELISA in Behcet's
      Disease.

PMID- 29593453
TI  - Short Term Hyperthermia Prevents Activation of Proinflammatory Genes in Type B
      Synoviocytes by Blocking the Activation of the Transcription Factor NF-kappaB.
AB  - The aim of this study was to investigate the effect and mechanisms of short term
      hyperthermia on a series of proinflammatory genes in type-B-synoviocytes
      (fibroblast like synoviocytes - FLS). In vitro experiments demonstrate that
      exposure of FLS to elevated temperatures for the duration of 30 minutes prevents
      activation of a series of genes with proinflammatory properties. Exposure to
      hyperthermia reduces IL-1f3 induced PGE2 release, suppresses activation of the
      adhesion molecules VCAM-1, ICAM-1, the cytokines TNFa, IL-1a, IL-1p, IL-8 as well
      as COX-2 protein synthesis. Real time RT-PCR showed that hyperthermia altered
      gene expression at the transcriptional level. As to the mechanism of inhibition,
      EMSA experiments demonstrated that exposure of FLS to hyperthermia prevents IL
      1f3 induced NF-kappaB translocation and subsequent DNA binding. Many mechanisms
      have been shown to be involved in hyperthermia mediated effects on NF-kappaB-DNA
      interactions. We demonstrated by Western blot experiments that in FLS,
      hyperthermia prevents the phosphorylation and subsequent degradation of
      IkappaBCC, therefore retaining the NF-kappaB complex in the cytoplasm. Such data
      might, at least in part, explain and provide a rationale for treating
      inflammation e.g. associated with rheumatoid arthritis by balneological means.

PMID- 29593454
TI  - Expanding and Improving the Service for Testing Single Embryonic Cells by
      Preimplantation Genetic Haplotyping.
AB  - The problem of having offspring with inherited diseases can be resolved in some
      cases through preimplantation genetic diagnosis (PGD). Spinal Muscular Atrophy
      (SMA) is one of these diseases. In my short term visit to Guy's Hospital in
      London, I set up a panel of markers which can be used for preimplantion genetic
      haplotyping in affected families with this pathology.

PMID- 29593455
TI  - ABO Mistyping of cis-AB Blood Group by the Automated Microplate Technique.
AB  - Background: The cis-AB phenotype, although rare, is the relatively most frequent
      of ABO subgroups in Koreans. To prevent ABO mistyping of cis-AB samples, our
      hospital has applied a combination of the manual tile method with automated
      devices. Herein, we report cases of ABO mistyping detected by the combination
      testing system. Methods: Cases that showed discrepant results by automated
      devices and the manual tile method were evaluated. These samples were also tested
      by the standard tube method. The automated devices used in this study were a
      QWALYS-3 and Galileo NEO. Exons 6 and 7 of the ABO gene were sequenced. Results:
      13 cases that had the cis-AB allele showed results suggestive of the cis-AB
      subgroup by manual methods, but were interpreted as AB by either automated
      device. This happened in 87.5% of these cases by QWALYS-3 and 70.0% by Galileo
      NEO. Genotyping results showed that 12 cases were ABO*cis-AB01/ABO*O01 or ABO*cis
      AB01/ABO*O02, and one case was ABO*cis-AB01/ ABO*A102. Conclusion: Cis-AB samples
      were mistyped as AB by the automated microplate technique in some cases. We
      suggest that the manual tile method can be a simple supplemental test for the
      detection of the cis-AB phenotype, especially in countries with relatively high
      cis-AB prevalence.

PMID- 29593456
TI  - Robust Production of Cytomegalovirus pp65-Specific T Cells Using a Fully
      Automated IFN-gamma Cytokine Capture System.
AB  - Background: Cytomegalovirus(CMV)-related diseases are a serious cause of
      morbidity and mortality following hematopoietic stem cell transplantation (HSCT).
      CMV-specific cytotoxic T lymphocytes (CMV-CTLs) have been reported as an
      alternative to antiviral drugs that provide long-term CMV-specific immunity
      without major side effects. However, their application has been limited by the
      prolonged manufacturing process required. Methods: In this study, we applied the
      IFN-gamma cytokine capture system (CCS) using the fully automated CliniMACS
      Prodigy device for rapid production of CMV-CTLs, which may be applicable in
      clinically urgent CMV-related diseases. Five validation runs were performed using
      apheresis samples from randomly selected CMV-seropositive healthy blood donors.
      Successive processes, including antigen stimulation, anti-IFN-gamma labeling,
      magnetic enrichment and elution, were then performed automatically using the
      CliniMACS Prodigy, which took approximately 13 h. Results: The original apheresis
      samples consisted mainly of CD45RA+ CD62L+ naive T cells as well as 0.3% IFN
      gamma-secreting CD3+ T cells that showed a response to the CMV pp65 antigen (CD3+
      IFN-gamma+ cells). Following IFN-gamma enrichment, the target fraction contained
      51.3% CD3+ IFN-gamma+ cells with a reduction in naive T cells and selection of
      CD45RA- CD62L- and CD45RA+ CD62L- memory T cells. Furthermore, extended culture
      of these isolated cells revealed functional activity, including efficient
      proliferation, sustained antigen-specific IFN-gamma secretion, and cytotoxicity
      against pp65-pulsed target cells. Conclusion: The findings reported here suggest
      that the IFN-gamma CCS by the CliniMACS Prodigy is a simple and robust approach
      to produce CMV-CTLs, which may be applicable for the treatment of clinically
      urgent CMV-related diseases.

PMID- 29593457
TI  - Platelet Count before Peripheral Blood Stem Cell Mobilization Is Associated with
      the Need for Plerixafor But Not with the Collection Result.
AB  - Background: A low platelet count before mobilization has recurrently been
      identified as risk factor for poor mobilization. Methods: To determine the
      relevance of this finding for peripheral blood stem cell (PBSC) mobilization,
      including pre-emptive or rescue plerixafor in the case of poor mobilization, we
      retrospectively analyzed all patients undergoing PBSC collection at our
      institution between January 2014 and December 2015 (n = 380). Results: In total,
      99% of the patients (377/380) successfully collected a minimum of 2 * 106 CD34+
      cells/kg body weight sufficient for a single transplant. Rescue or pre-emptive
      plerixafor was administered to 11% of the patients (42/380). No correlations
      between the platelet count before mobilization and the number of peripheral blood
      CD34+ cells or the CD34+ cell collection result were detected in the entire
      population or the subgroups according to diagnosis (newly diagnosed multiple
      myeloma, relapsed multiple myeloma, lymphoma, amyloid light-chain amyloidosis,
      sarcoma, or germ cell tumor). However, patients requiring pre-emptive or rescue
      plerixafor had a significantly lower platelet count before mobilization (217/nl
      vs. 245/nl; p = 0.004). Conclusion: With the current state of the art PBSC
      mobilization strategies, the platelet count before mobilization was not
      associated with the CD34+ cell collection result but was associated with the need
      for pre-emptive or rescue application of plerixafor.

PMID- 29593458
TI  - Reactive Oxygen Species Generated by CD45-Cells Distinct from Leukocyte
      Population in Platelet Concentrates Is Correlated with the Expression and Release
      of Platelet Activation Markers during Storage.
AB  - Background: Platelet stimulation with agonists is accompanied by the generation
      of reactive oxygen species (ROS) which promotes further platelet activation and
      aggregation. Considering different cell populations in platelet concentrates
      (PCs), this study investigates the correlation of ROS generation with the
      expression and release of platelet activation markers during storage. Methods:
      Samples obtained from 6 PCs were subjected to flow cytometry and ELISA to
      evaluate the expression and shedding of platelet P-selectin or CD40L during
      storage. Intracellular ROS were detected in either CD45- or CD45+ population by
      flow cytometry using dihydrorhodamine 123, while ROS production was analyzed in
      both P-selectin+ or P-selectin- and CD40L+ or CD40L- populations. To further
      evaluate the correlation between ROS generation and release function, TRAP
      stimulated platelets were also subjected to flow cytometry analysis. Results: ROS
      detected in the CD45-population (leukocyte-free platelets) was significantly
      increased by fMLP and PMA. P-selectin- or CD40L- platelet did not show
      significant amount of ROS. Total ROS generation was significantly increased
      during platelet storage (day 0 vs. day 5; p = 0.0002) while this increasing
      pattern was directly correlated with the expression of P-selectin (r = 0.72; p =
      0.0001) and CD40L (r = 0.69; p = 0.0001). ROS generations were significantly
      correlated with ectodomain shedding of these pro-inflammatory molecules.
      Conclusion: Our data confirmed increasing levels of intracellular ROS generation
      in both platelets (CD45-) and platelet-leukocyte aggregates (CD45+) during PC
      storage. The amount of detected ROS is directly correlated with platelet
      activation and release in each population while platelet-leukocyte aggregates
      generate higher levels of ROS than single platelets.

PMID- 29593459
TI  - Post-Operative Iron Carboxymaltose May Have an Effect on Haemoglobin Levels in
      Cardiothoracic Surgical Patients on the ICU - an Observational Pilot Study about
      Anaemia Treatment with Intravenous Iron.
AB  - Background: Post-operative anaemia is associated with increased morbidity and
      mortality. Positive effects of post-operative intravenous iron (IVI) after
      elective orthopaedic, abdominal and genitourinary surgery have been reported. The
      current observational trial investigated the prevalence of post-operative
      anaemia, the effect of IVI on haemoglobin levels, the use of blood transfusions
      and diagnoses related to infections. Methods: 1,265 patients on five ICUs of
      Munster University Hospital were screened for post-operative anaemia. On one ICU,
      patients were screened for iron deficiency and, if indicated, supplemented with
      500 mg of ferric carboxymaltose. Primary outcome measures were haemoglobin
      levels, C-reactive protein, white blood cell count, transfusion requirements,
      documented infection and antibiotic treatment. Results: Anaemia was prevalent in
      86.2% of patients upon ICU admission. 429 patients were screened for iron
      deficiency anaemia. 95 patients were eligible, 35 were treated with IVI. An
      increase of +0.4 g/dl in Hb levels 7 days after IVI compared to -0.1 g/dl in non
      treated anaemic patients was observed. The number of RBC transfusions, ICD codes
      related to infections and infectious parameters were similar between groups.
      Conclusions: IVI treatment was safe and resulted in higher median Hb levels.
      Randomized controlled trials are required to support the hypotheses of this
      study.

PMID- 29593460
TI  - Association of IL-6 C-572G Gene Polymorphism with Anti-E Production.
AB  - Background: Interleukin 6 (IL-6) is involved in regulation of immunoglobulin
      production. The aim of this study was to investigate the association between IL-6
      single nucleotide polymorphisms (SNPs) in the IL-6 promoter and anti-E in red
      blood cell (RBC) transfusion recipients. Methods: 50 healthy subjects, 54
      patients with RBC alloantibody anti-E (responders), and 45 patients without
      alloantibody (non-responders) were recruited. All patients were E antigen
      negative. Results: All healthy subjects and patients had GG at -174 position of
      IL-6 gene. In our healthy subjects, the frequency of the -572 CC genotype was
      58%, that of the -572 CG genotype 38%, and that of the -572 GG genotype 4%. The
      frequency of G allele of -572 SNP in responders was significantly higher than
      that in non-responders, (31.5 vs. 16.7%; p = 0.020). The frequency of -572 G
      positive genotypes (CG and GG) in responders was also significantly higher than
      that in non-responders, (55.6 vs. 31.1%; p = 0.016). The relative risk of RBC
      alloimmunization for patients with the -572 G-positive genotype was significantly
      higher than that of patients with the -572 CC genotype, (1.771 vs. 0.640; p =
      0.016). Conclusion: IL-6 C-572G gene polymorphism is significantly associated
      with anti-E production, with the allele G as a risk allele.

PMID- 29593461
TI  - Interaction of Platelet-Derived Microparticles with a Human B-Lymphoblast Cell
      Line: A Clue for the Immunologic Function of the Microparticles.
AB  - Background: Platelets are blood cells with extensive capabilities in hemostasis.
      They also play a central role in the development of innate and adaptive immune
      responses. Little information exists about the immunostimulatory role of platelet
      derived microparticles (Plt-MPs). To further elucidate this issue, we conducted
      this study using the B-lymphoblast cell line 'Daudi' as an available surrogate
      cell line for peripheral blood B lymphocytes. This cell line does not produce
      immunoglobulins (Igs) and has low expression of activation markers. Methods: Plt
      MPs were isolated from platelet concentrate (PC) using a multi-step
      centrifugation method. Daudi cells were treated with Plt-MPs in the culture
      medium while no treatment was given to the control cells. During 5-day co
      culture, Daudi cells were evaluated for the Ig production and the expression of
      the cell surface markers CD86, CD27, and IgD. Results: An increase was observed
      for the production of IgG and the expression of CD27 and CD86 on Daudi cells in
      response to Plt-MPs, whereas the IgD level was decreased. The response of Daudi
      cells was dependent on the concentration of Plt-MPs and the time of their
      isolation from PCs during storage. The differences of the variables were
      significant between the treatment and control groups. Conclusion: Plt-MPs could
      induce the activation and differentiation of immortalized cells of B-cell origin.
      Thus it is conceivable that Plt-MPs may play a significant role as immortalized
      cell activators in human monoclonal antibody technology in near future.

PMID- 29593462
TI  - ABO, Rhesus, and Kell Antigens, Alleles, and Haplotypes in West Bengal, India.
AB  - Background: Few studies have documented the blood group antigens in the
      population of eastern India. Frequencies of some common alleles and haplotypes
      were unknown. We describe phenotype, allele, and haplotype frequencies in the
      state of West Bengal, India. Methods: We tested 1,528 blood donors at the Medical
      College Hospital, Kolkata. The common antigens of the ABO, Rhesus, and Kell blood
      group systems were determined by standard serologic methods in tubes. Allele and
      haplotype frequencies were calculated with an iterative method that yielded
      maximum-likelihood estimates under the assumption of a Hardy-Weinberg
      equilibrium. Results: The prevalence of ABO antigens were B (34%), O (32%), A
      (25%), and AB (9%) with ABO allele frequencies for O = 0.567, A = 0.189, and B =
      0.244. The D antigen (RH1) was observed in 96.6% of the blood donors with RH
      haplotype frequencies, such as for CDe = 0.688809, cde = 0.16983 and CdE =
      0.000654. The K antigen (K1) was observed in 12 donors (0.79%) with KEL allele
      frequencies for K = 0.004 and k = 0.996. Conclusions: For the Bengali population
      living in the south of West Bengal, we established the frequencies of the major
      clinically relevant antigens in the ABO, Rhesus, and Kell blood group systems and
      derived estimates for the underlying ABO and KEL alleles and RH haplotypes. Such
      blood donor screening will improve the availability of compatible red cell units
      for transfusion. Our approach using widely available routine methods can readily
      be applied in other regions, where the sufficient supply of blood typed for the
      Rh and K antigens is lacking.

PMID- 29593463
TI  - Young Blood Rejuvenates Old Bodies: A Call for Reflection when Moving from Mice
      to Men.
AB  - Connecting the circulatory system of old and young mice (parabiosis) is
      documented to have rejuvenating effects on cells, tissues, organs, and functions.
      A wide range of benefits are envisioned. Blood-based rejuvenation can come to
      totally change population health and aging. The first blood rejuvenation studies
      on humans with Alzheimer's disease have started. It puts blood at the center of
      therapy and revitalizes the historical line of humoral pathology from Hippocrates
      and Harvey, creating a new type of 'bloodletting.' However, moving from mice to
      men requires careful consideration. Parabiosis actualizes well-known ethical
      challenges, such as just distribution of health care, avoiding disparities, and
      providing equal access to health care resources, as well as issues of human
      enhancement. However, it also poses new problems. Using internal substances in
      some persons as means to rejuvenate others calls for ethical reflection. New type
      of 'blood bonds' may result from the continuous demand for specific types of
      blood. Even if rejuvenating substances from blood may be artificially and cheaply
      produced and justly distributed, problems arise: survival may have to be balanced
      against reproduction, as reproductive age increases. Eternal youth and endless
      bliss have always been vital human dreams. Although parabiosis may bring us
      closer to the fountain of youth than ever, it is still too early to provide full
      fledged assessments of its implications or to foresee how it will change health,
      aging, medicine, and society. However, in order to bring our reflective abilities
      on par with our technical skills, we need to start reflection now.

PMID- 29593465
TI  - Experience of a Tertiary-Level Urology Center in the Clinical Urological Events
      of Rare and Very Rare Incidence. I. Surgical Never Events: 1. Urological Wrong
      Surgery Catastrophes and Disabling Complications.
AB  - Introduction: Surgical never events are preventable harmful non-intentional human
      errors. Urology is a common surgical specialty for their occurrence. Patients and
      Methods: A retrospective search of our center's data was done during the period
      2006-2016 for surgical never events. Each included case was studied for the
      primary diagnosis, procedure, and subspecialty, never event type and timing,
      needed extra-interventions, urologist/procedure proportioning, outcomes, and
      possible underlying causes of the event. Results: Of more than 55,000 different
      urological interventions, 61 patients were involved in never events. Wrong
      procedures represented 75% of the never events, and endourology and urolithiasis
      subspecialties were more often involved. The main detectable underlying factor
      was the disproportion between the levels of the procedure class and the
      qualification of the urologist (41%). Thirty-four cases had extra-procedures. The
      short-term harm effect represented the final outcome in 42% of all events. Death,
      permanent organ loss, and long-term harm represented 20, 15, and 23%,
      respectively. Conclusion: Urological surgical never events are rare, but their
      final outcomes could be catastrophic, even leading to death.

PMID- 29593466
TI  - Using the Modified Clavien Grading System to Classify Complications of
      Percutaneous Nephrolithotomy.
AB  - Purpose: A modified Clavien classification system has been proposed to grade
      perioperative complications. We share our experience in grading the complications
      of percutaneous nephrolithotomy (PNL), according to this new classification.
      Methods: A total of 809 PNLs performed between 2010 and 2014 were reviewed
      retrospectively. The modified Clavien classification system, which classifies the
      perioperative complications into 5 grades, was applied. Grade wise comparison of
      complications between the patients with simple and complex calculi was done. We
      also carried out a univariate analysis of different predictors of complications
      after surgery. Results: A total of 253 perioperative complications were observed
      in 237 (29.29%) patients. Most complications were related to bleeding and urinary
      leakage. Patients with complex calculi had significantly more number of
      complications across all Clavien groups. In a univariate analysis, positive
      preoperative urine culture and multiple access for stone clearance were
      identified to be the independent predictors of complications. Conclusion: The
      modified Clavien system is a simplistic grading system for classification of
      postoperative complications. However, it suffers from various shortcomings.
      Therefore, till the proposition of a more comprehensive classification system,
      the modified Clavien system is useful for reporting the complications and short
      term outcomes of PNL.

PMID- 29593464
TI  - The Emerging Role of Inflammasomes as Central Mediators in Inflammatory Bladder
      Pathology.
AB  - Irritative voiding symptoms (e.g. increased frequency and urgency) occur in many
      common pathologic conditions such as urinary tract infections and bladder outlet
      obstruction, and these conditions are well-established to have underlying
      inflammation that directly triggers these symptoms. However, it remains unclear
      as to how such diverse stimuli individually generate a common inflammatory
      process. Jurg Tschopp provided substantial insight into this conundrum when,
      working with extracts from THP-1 cells, he reported the existence of the
      inflammasome. He described it as a structure that senses multiple diverse signals
      from intracellular/extracellular sources and pathogens and triggers inflammation
      by the maturation and release of the pro-inflammatory cytokines interleukin-1beta
      and interleukin-18. Recently, many of these sensors were found in the bladder and
      the nucleotide-binding domain, leucine-rich-containing family, pyrin domain
      containing-3, has been shown to be a central mediator of inflammation in several
      urological diseases. In this review, we introduce the nucleotide-binding domain,
      leucine-rich-containing family, pyrin domaincontaining-3 inflammasome, highlight
      its emerging role in several common urologic conditions, and speculate on the
      potential involvement of other inflammasomes in bladder pathology.

PMID- 29593467
TI  - Associations of Transitional Zone Volume with Intraprostatic Chronic Inflammation
      and Prostate Cancer Risk in Patients Undergoing a First Random Biopsy Set.
AB  - Objectives: To investigate associations of the transitional zone volume (TZV)
      with intraprostatic chronic inflammatory infiltrate (CII) and prostate cancer
      (PCa) risk in patients undergoing a first random biopsy set. Materials and
      Methods: The study included a homogenous population of 596 patients. The volume
      of the prostate and TZV were separately measured. Independent associations were
      investigated by multivariate logistic regression analysis. Results: The median
      TZV was 18 ml, CII was detected in 157 cases (26.3%), and PCa was present in 292
      patients (49%). TZV was the only independent clinical factor associated with CII
      risk (OR = 1.014). After correcting for CII (OR = 0.276; p < 0.0001), independent
      factors associated with PCa risk included age (OR = 1.066), prostate specific
      antigen (OR = 1.177), TZV (OR = 0.919), and an abnormal digital rectal exam (OR =
      2.024). Conclusion: In a patient population undergoing a first random prostate
      biopsy set because of suspected cancer, independent associations were detected
      among TZV, CII, and PCa. The association between TZV and CII was direct, but the
      relation between TZV and PCa was inverse. The measurement of the volume of the
      transitional zone was a useful parameter for evaluating chronic intraprostatic
      inflammation and PCa risk.

PMID- 29593468
TI  - The Effect of Human Chorionic Gonadotropin Therapy on Semen Parameters and
      Pregnancy Rate after Varicocelectomy.
AB  - Introduction: To study the stimulating effect of human chorionic gonadotropin
      (hCG) on spermatogenesis in patients with varicocele and infertility undergoing
      varicocelectomy. Materials and Methods: In the study, 188 infertile patients with
      varicocele were included. Open inguinal varicocelectomy was performed. They were
      randomized into 2 groups and hCG (91 patients) was administered intramuscularly
      by dosage of 5,000 international units every week for 3 months. A semen analysis
      was obtained at 6 months, post-operatively and cases were followed for 2 years
      for pregnancy report. Results: Semen analysis of the patients shows a significant
      improvement in all parameters 6 months after varicocelectomy without any
      superiority between the 2 groups. During the follow-up, 56 couples (61.5%) in hCG
      treated and 22 couples (22.7%) in the group treated only by varicocelectomy
      achieved pregnancy. Patients treated with varicocelectomy plus hCG therapy had a
      significant superior pregnancy rate compared to the other group (P=0.0001).
      Conclusion: Administration of hCG in this group of infertile patients might be
      helpful in order to enhance pregnancy rate. However some more conclusive studies
      are needed to be able to recommend such therapy for infertile men due to
      varicocele.

PMID- 29593469
TI  - Pilot Study to Determine Optimal Stent Duration Following Ureteroscopy: Three
      versus Seven days.
AB  - Background/Aims: Many providers elect to place a stent following ureteroscopy for
      nephrolithiasis, but little data exists on the optimal duration to leave a stent.
      We sought to determine whether there are any differences in post-operative
      outcomes for patients with a 3 versus 7-day stent following ureteroscopy.
      Methods: We retrospectively reviewed 247 patients who underwent unilateral
      ureteroscopy with lithotripsy, 79 of whom removed a stent with an extraction
      string at 3 or 7 days post-operatively. These 2 groups were compared with regard
      to demographic information, pre-operative variables, and post-operative outcomes.
      Results: Of all patients, 33% experienced a post-procedure related event (phone
      call, extra clinic visit, and emergency department visit) within 30 days of their
      procedure, 39% of 3-day stent patients compared to 21% of 7-day patients (p =
      0.11). Within the 3 days following stent removal, 3-day stent patients were
      significantly more likely to have a post-procedure related event than 7-day
      patients (23 vs. 3%, p = 0.026). Conclusion: One third of patients with a post
      operative ureteral stent will seek medical care in the 30 days following
      ureteroscopy. Leaving a stent for 3 versus 7 days may lead to worse outcomes with
      regard to post-operative events and fank pain.

PMID- 29593470
TI  - Comparison of Safety, Efficacy and Cost Effectiveness of Photoselective
      Vaporization with Bipolar Vaporization of Prostate in Benign Prostatic
      Hyperplasia.
AB  - Objectives: To compare bipolar vaporization of prostate (BPVP) with
      photoselective vaporization (PVP) of prostate in the surgical management of
      benign prostatic hyperplasia in terms of safety, efficacy and cost effectiveness.
      Methods: Data was analyzed retrospectively for patients who underwent either PVP
      or BPVP between August 2012 to July 2014 for prostate size <= 80 ml. Preoperative
      and postoperative period values along with details like operative time, blood
      loss, hospitalization days, catheter removal time, blood transfusion and etc.,
      were noted down. International prostatic symptom score, quality of life scores,
      post void residue, and maximum flow rate were recorded preoperatively and
      postoperatively at each follow-up visit. Follow-up was performed at 1, 3, 6, 12
      and 18 months. Results: Similar preoperative characteristics were observed in all
      the study arms. Hemoglobin drop, transfusion rate, catheter time and hospital
      days were similar in both the groups. The follow-up data indicates sustainable
      significant improvement in international prostatic symptom score, quality of
      life, post void residue and maximum flow rate in both the groups. As expected the
      cost of the procedure was significantly more in PVP group as compared to BPVP
      group (p < 0.01). Neither group had severe perioperative complications and no
      blood transfusion was required in both the groups. Conclusion: Both PVP and BPVP
      were safe and effective alternatives in men requiring surgery for benign
      prostatic hyperplasia including patients who were on anticoagulants.
      Additionally, BPVP has the advantage of being significantly cheaper and therefore
      it can be more useful in developing countries.

PMID- 29593471
TI  - Rare Metastatic Testicular Cancer in a Veteran.
AB  - Testicular yolk sac tumor (YST) is a nonseminomatous germ cell tumor that
      predominantly affects prepubescent boys. Pure endometrioid variant YST is rare,
      with only 1 report in the literature. We present the first reported case of en
      dometrioid variant YST with mature teratoma in the retro-peritoneal specimen.

PMID- 29593472
TI  - Call for Nomination of Members of the International Standing Committee of Human
      Cytogenomic Nomenclature.

PMID- 29593473
TI  - Cerebral Cavernous Malformations: An Update on Prevalence, Molecular Genetic
      Analyses, and Genetic Counselling.
AB  - Based on the latest gnomAD dataset, the prevalence of symptomatic hereditary
      cerebral cavernous malformations (CCMs) prone to cause epileptic seizures and
      stroke-like symptoms was re-evaluated in this review and calculated to be 1:5,400
      1:6,200. Furthermore, state-of-the-art molecular genetic analyses of the known
      CCM loci are described which reach an almost 100% mutation detection rate for
      familial CCMs if whole genome sequencing is performed for seemingly mutation
      negative families. An update on the spectrum of CCM1, CCM2, and CCM3 mutations
      demonstrates that deep-intronic mutations and submicroscopic copy-number neutral
      genomic rearrangements are rare. Finally, this review points to current
      guidelines on genetic counselling, neuroimaging, medical as well as neurosurgical
      treatment and highlights the formation of active patient organizations in various
      countries.

PMID- 29593475
TI  - Language and Cognitive Impairment Associated with a Novel p.Cys63Arg Change in
      the MED13L Transcriptional Regulator.
AB  - Mutations in the MED13L gene, which encodes a subunit of a transcriptional
      regulatory complex, result in a complex phenotype entailing physical and
      cognitive anomalies. Deep language impairment has been reported in affected
      individuals, mostly in patients with copy number variations. We report on a child
      with a nonsynonymous p.Cys63Arg change in MED13L (chr12:116675396A>G, GRCh37) who
      exhibits profound language impairment in the expressive domain, cognitive delay,
      behavioral disturbances, and an autism-like phenotype. Because of the brain areas
      in which MED13L is expressed and because of the functional links between MED13L
      and the products of selected candidate genes for cognitive disorders involving
      language deficits, the proband's linguistic phenotype may result from changes in
      a functional network important for language development and evolution.

PMID- 29593476
TI  - Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases
      in a Cohort of Brazilian Patients with Skeletal Dysplasia.
AB  - Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) cause
      achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia types
      I and II (TDI/TDII). In this study, we performed a genetic study of 123 Brazilian
      patients with these phenotypes. Mutation hotspots of the FGFR3 gene were PCR
      amplified and sequenced. All cases had recurrent mutations related to ACH, HCH,
      TDI or TDII, except for 2 patients. One of them had a classical TDI phenotype but
      a typical ACH mutation (c.1138G>A) in combination with a novel c.1130T>C mutation
      predicted as being pathogenic. The presence of the second c.1130T>C mutation
      likely explained the more severe phenotype. Another atypical patient presented
      with a compound phenotype that resulted from a combination of ACH and X-linked
      spondyloepiphyseal dysplasia tarda (OMIM 313400). Next-generation sequencing of
      this patient's DNA showed double heterozygosity for a typical de novo ACH
      c.1138G>A mutation and a maternally inherited TRAPPC2 c.6del mutation. All
      mutations were confirmed by Sanger sequencing. A pilot study using high
      resolution melting (HRM) technique was also performed to confirm several
      mutations identified through sequencing. We concluded that for recurrent FGFR3
      mutations, HRM can be used as a faster, reliable, and less expensive genotyping
      test than Sanger sequencing.

PMID- 29593474
TI  - A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively
      Parallel Sequencing.
AB  - The overgrowth syndromes are important to diagnose, not just for accurate genetic
      counseling, but also for knowledge surrounding cancer surveillance and prognosis.
      There has been a recent expansion in the number of genes associated with a
      mendelian overgrowth phenotype, so this review updates previous classifications
      of overgrowth syndromes. We also describe a clinical and molecular approach to
      the investigation of individuals presenting with overgrowth. This review aims to
      assist the clinical diagnosis of generalized overgrowth syndromes by outlining
      the salient features of well-known overgrowth syndromes alongside the many
      syndromes that have been discovered and classified more recently. We provide key
      clinical "handles" to aid clinical diagnosis and a list of genes to aid with
      panel design when using next generation sequencing, which we believe is
      frequently needed due to the overlapping phenotypic features seen between
      overgrowth syndromes.

PMID- 29593477
TI  - Novel Nonsense Mutation in SLC39A13 Initially Presenting as Myopathy: Case Report
      and Review of the Literature.
AB  - Myopathies comprise a heterogeneous group of disorders characterized by variable
      phenotypes. The increasing use of next-generation sequencing allows
      identification of the causative genes in a much higher percentage of patients
      with hereditary muscle disorders and also illustrates a considerable degree of
      overlap with other clinical entities, including connective tissue disorders.
      Here, we present a 14-year-old German patient who was initially suspected to
      suffer from myopathy based on his clinical, radiological, and muscle biopsy
      findings. Exome sequencing revealed a novel homozygous nonsense mutation in the
      SLC39A13 gene, causative for spondylocheiro dysplastic Ehlers Danlos syndrome
      (SCD-EDS), suggesting a connective tissue disorder. Including our patient, only 9
      affected individuals from 4 families have been described for SCD-EDS so far. The
      previously reported patients did not show obvious evidence of myopathy,
      suggesting a broader clinical presentation than originally suspected. We
      summarize herein the current knowledge on clinical features as well as
      pathophysiological pathways for this rare connective tissue disease and discuss
      the high degree of clinical overlap between myopathic and connective tissue
      disorders.

PMID- 29593479
TI  - #RAREvolution - Stand up for Scientific Research on Rare Diseases.

PMID- 29593480
TI  - REACT Congress Program 2018.

PMID- 29593478
TI  - A Novel GMPPA Mutation in Two Adult Sisters with Achalasia, Alacrima, Short
      Stature, Dysmorphism, and Intellectual Disability.
AB  - The alacrima, achalasia, and mental retardation syndrome (AAMR) is a newly
      described autosomal recessive disorder characterized by the onset of these 3 main
      features at birth or in early infancy. At present, only 16 cases have been
      reported. Recently, it was shown that AAMR is due to mutations in the guanosine
      diphosphate (GDP)-mannose pyrophosphorylase A (GMPPA) gene. These mutations
      induce a significant GDP-mannose overload, which may affect protein
      glycosylation. Herein, for the first time, we describe 2 adult sisters with AAMR
      with a previously not reported deleterious homozygous missense mutation c.1118G>C
      (p.Arg373Pro) in the GMPPA gene, born to healthy consanguineous heterozygous
      parents from an ancient endogamous population. The main symptoms in both sisters
      started soon after birth with achalasia and feeding difficulties, requiring
      surgical treatment. Both sisters showed alacrima identified during the first
      months of life, delayed psychomotor development, speech delay, facial
      dysmorphism, limb defects, short stature, and moderate intellectual disability.
      Alacrima and feeding difficulties due to achalasia during the neonatal period or
      first months of life, in the absence of adrenal cortical insufficiency, should
      spur to investigate AAMR by sequencing the GMPPA gene.

PMID- 29593481
TI  - Using Support Vector Machine on EEG for Advertisement Impact Assessment.
AB  - The advertising industry depends on an effective assessment of the impact of
      advertising as a key performance metric for their products. However, current
      assessment methods have relied on either indirect inference from observing
      changes in consumer behavior after the launch of an advertising campaign, which
      has long cycle times and requires an ad campaign to have already have been
      launched (often meaning costs having been sunk). Or through surveys or focus
      groups, which have a potential for experimental biases, peer pressure, and other
      psychological and sociological phenomena that can reduce the effectiveness of the
      study. In this paper, we investigate a new approach to assess the impact of
      advertisement by utilizing low-cost EEG headbands to record and assess the
      measurable impact of advertising on the brain. Our evaluation shows the desired
      performance of our method based on user experiment with 30 recruited subjects
      after watching 220 different advertisements. We believe the proposed SVM method
      can be further developed to a general and scalable methodology that can enable
      advertising agencies to assess impact rapidly, quantitatively, and without bias.

PMID- 29593482
TI  - Aminochrome Induces Irreversible Mitochondrial Dysfunction by Inducing Autophagy
      Dysfunction in Parkinson's Disease.

PMID- 29593483
TI  - Computing Generalized Matrix Inverse on Spiking Neural Substrate.
AB  - Emerging neural hardware substrates, such as IBM's TrueNorth Neurosynaptic
      System, can provide an appealing platform for deploying numerical algorithms. For
      example, a recurrent Hopfield neural network can be used to find the Moore
      Penrose generalized inverse of a matrix, thus enabling a broad class of linear
      optimizations to be solved efficiently, at low energy cost. However, deploying
      numerical algorithms on hardware platforms that severely limit the range and
      precision of representation for numeric quantities can be quite challenging. This
      paper discusses these challenges and proposes a rigorous mathematical framework
      for reasoning about range and precision on such substrates. The paper derives
      techniques for normalizing inputs and properly quantizing synaptic weights
      originating from arbitrary systems of linear equations, so that solvers for those
      systems can be implemented in a provably correct manner on hardware-constrained
      neural substrates. The analytical model is empirically validated on the IBM
      TrueNorth platform, and results show that the guarantees provided by the
      framework for range and precision hold under experimental conditions. Experiments
      with optical flow demonstrate the energy benefits of deploying a reduced
      precision and energy-efficient generalized matrix inverse engine on the IBM
      TrueNorth platform, reflecting 10* to 100* improvement over FPGA and ARM core
      baselines.

PMID- 29593484
TI  - Neurogenomic Profiling Reveals Distinct Gene Expression Profiles Between Brain
      Parts That Are Consistent in Ophthalmotilapia Cichlids.
AB  - The detection of external and internal cues alters gene expression in the brain
      which in turn may affect neural networks that underly behavioral responses.
      Previous studies have shown that gene expression profiles differ between major
      brain regions within individuals and between species with different morphologies,
      cognitive abilities and/or behaviors. A detailed description of gene expression
      in all macroanatomical brain regions and in species with similar morphologies and
      behaviors is however lacking. Here, we dissected the brain of two cichlid species
      into six macroanatomical regions. Ophthalmotilapia nasuta and O. ventralis have
      similar morphology and behavior and occasionally hybridize in the wild. We use 3'
      mRNA sequencing and a stage-wise statistical testing procedure to identify
      differential gene expression between females that were kept in a social setting
      with other females. Our results show that gene expression differs substantially
      between all six brain parts within species: out of 11,577 assessed genes, 8,748
      are differentially expressed (DE) in at least one brain part compared to the
      average expression of the other brain parts. At most 16% of these DE genes have
      |log2FC| significantly higher than two. Functional differences between brain
      parts were consistent between species. The majority (61-79%) of genes that are DE
      in a particular brain part were shared between both species. Only 32 genes show
      significant differences in fold change across brain parts between species. These
      genes are mainly linked to transport, transmembrane transport, transcription (and
      its regulation) and signal transduction. Moreover, statistical equivalence
      testing reveals that within each comparison, on average 89% of the genes show an
      equivalent fold change between both species. The pronounced differences in gene
      expression between brain parts and the conserved patterns between closely related
      species with similar morphologies and behavior suggest that unraveling the
      interactions between genes and behavior will benefit from neurogenomic profiling
      of distinct brain regions.

PMID- 29593486
TI  - Commentary: Consistency of EEG source localization and connectivity estimates.

PMID- 29593487
TI  - Hearing the Sound in the Brain: Influences of Different EEG References.
AB  - If the scalp potential signals, the electroencephalogram (EEG), are due to neural
      "singers" in the brain, how could we listen to them with less distortion? One
      crucial point is that the data recording on the scalp should be faithful and
      accurate, thus the choice of reference electrode is a vital factor determining
      the faithfulness of the data. In this study, music on the scalp derived from data
      in the brain using three different reference electrodes were compared, including
      approximate zero reference-reference electrode standardization technique (REST),
      average reference (AR), and linked mastoids reference (LM). The classic music
      pieces in waveform format were used as simulated sources inside a head model, and
      they were forward calculated to scalp as standard potential recordings, i.e.,
      waveform format music from the brain with true zero reference. Then these scalp
      music was re-referenced into REST, AR, and LM based data, and compared with the
      original forward data (true zero reference). For real data, the EEG recorded in
      an orthodontic pain control experiment were utilized for music generation with
      the three references, and the scale free index (SFI) of these music pieces were
      compared. The results showed that in the simulation for only one source,
      different references do not change the music/waveform; for two sources or more,
      REST provide the most faithful music/waveform to the original ones inside the
      brain, and the distortions caused by AR and LM were spatial locations of both
      source and scalp electrode dependent. The brainwave music from the real EEG data
      showed that REST and AR make the differences of SFI between two states more
      recognized and found the frontal is the main region that producing the music. In
      conclusion, REST can reconstruct the true signals approximately, and it can be
      used to help to listen to the true voice of the neural singers in the brain.

PMID- 29593485
TI  - "Till Death Do Us Part": A Potential Irreversible Link Between Aberrant Cell
      Cycle Control and Neurodegeneration in the Adult Olfactory Bulb.
AB  - Adult neurogenesis (AN) is an ongoing developmental process that generates
      newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout
      life and significantly contributes to brain plasticity. Adult neural stem and
      progenitor cells (aNSPCs) are relatively limited in number and fate and are
      spatially restricted to the subventricular zone (SVZ) and the subgranular zone
      (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond
      cell cycle control and constitute key regulatory mechanisms involved in neuronal
      maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post
      mitotic neurons has been strongly linked to the abnormal pathophysiology in
      rodent models of neurodegenerative diseases with potential implications on the
      etiology and progression of such diseases in humans. Here, we present an overview
      of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by
      a comprehensive update of the distinct roles played by cell cycle proteins
      including major tumors suppressor genes in various steps during neurogenesis. We
      also discuss accumulating evidence underlining a strong link between abnormal
      cell cycle control, olfactory dysfunction and neurodegeneration in the adult and
      aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of
      cell cycle suppression and/or age-related insults as well as DNA damage can
      anticipate the development of neurodegenerative lesions and protein aggregates,
      (2) the age-related decline in SVZ and OE neurogenesis is associated with
      compensatory pro-survival mechanisms in the aging OB which are interestingly
      similar to those detected in Alzheimer's disease and Parkinson's disease in
      humans, and (3) the OB represents a well suitable model to study the early
      manifestation of age-related defects that may eventually progress into the
      formation of neurodegenerative lesions and, possibly, spread to the rest of the
      brain. Such findings may provide a novel approach to the modeling of
      neurodegenerative diseases in humans from early detection to progression and
      treatment as well.

PMID- 29593488
TI  - A Set of Functional Brain Networks for the Comprehensive Evaluation of Human
      Characteristics.
AB  - Many human characteristics must be evaluated to comprehensively understand an
      individual, and measurements of the corresponding cognition/behavior are
      required. Brain imaging by functional MRI (fMRI) has been widely used to examine
      brain function related to human cognition/behavior. However, few aspects of
      cognition/behavior of individuals or experimental groups can be examined through
      task-based fMRI. Recently, resting state fMRI (rs-fMRI) signals have been shown
      to represent functional infrastructure in the brain that is highly involved in
      processing information related to cognition/behavior. Using rs-fMRI may allow
      diverse information about the brain through a single MRI scan to be obtained, as
      rs-fMRI does not require stimulus tasks. In this study, we attempted to identify
      a set of functional networks representing cognition/behavior that are related to
      a wide variety of human characteristics and to evaluate these characteristics
      using rs-fMRI data. If possible, these findings would support the potential of rs
      fMRI to provide diverse information about the brain. We used resting-state fMRI
      and a set of 130 psychometric parameters that cover most human characteristics,
      including those related to intelligence and emotional quotients and social
      ability/skill. We identified 163 brain regions by VBM analysis using regression
      analysis with 130 psychometric parameters. Next, using a 163 * 163 correlation
      matrix, we identified functional networks related to 111 of the 130 psychometric
      parameters. Finally, we made an 8-class support vector machine classifiers
      corresponding to these 111 functional networks. Our results demonstrate that rs
      fMRI signals contain intrinsic information about brain function related to
      cognition/behaviors and that this set of 111 networks/classifiers can be used to
      comprehensively evaluate human characteristics.

PMID- 29593489
TI  - Listening Effort During Sentence Processing Is Increased for Non-native
      Listeners: A Pupillometry Study.
AB  - Current evidence demonstrates that even though some non-native listeners can
      achieve native-like performance for speech perception tasks in quiet, the
      presence of a background noise is much more detrimental to speech intelligibility
      for non-native compared to native listeners. Even when performance is equated
      across groups, it is likely that greater listening effort is required for non
      native listeners. Importantly, the added listening effort might result in
      increased fatigue and a reduced ability to successfully perform multiple tasks
      simultaneously. Task-evoked pupil responses have been demonstrated to be a
      reliable measure of cognitive effort and can be useful in clarifying those
      aspects. In this study we compared the pupil response for 23 native English
      speakers and 27 Italian speakers of English as a second language. Speech
      intelligibility was tested for sentences presented in quiet and in background
      noise at two performance levels that were matched across groups. Signal-to-noise
      levels corresponding to these sentence intelligibility levels were pre-determined
      using an adaptive intelligibility task. Pupil response was significantly greater
      in non-native compared to native participants across both intelligibility levels.
      Therefore, for a given intelligibility level, a greater listening effort is
      required when listening in a second language in order to understand speech in
      noise. Results also confirmed that pupil response is sensitive to speech
      intelligibility during language comprehension, in line with previous research.
      However, contrary to our predictions, pupil response was not differentially
      modulated by intelligibility levels for native and non-native listeners. The
      present study corroborates that pupillometry can be deemed as a valid measure to
      be used in speech perception investigation, because it is sensitive to
      differences both across participants, such as listener type, and across
      conditions, such as variations in the level of speech intelligibility.
      Importantly, pupillometry offers us the possibility to uncover differences in
      listening effort even when those do not emerge in the performance level of
      individuals.

PMID- 29593490
TI  - A Comparative Study of Standardized Infinity Reference and Average Reference for
      EEG of Three Typical Brain States.
AB  - The choice of different reference electrodes plays an important role in
      deciphering the functional meaning of electroencephalography (EEG) signals. In
      recent years, the infinity zero reference using the reference electrode standard
      technique (REST) has been increasingly applied, while the average reference (AR)
      was generally advocated as the best available reference option in previous
      classical EEG studies. Here, we designed EEG experiments and performed a direct
      comparison between the influences of REST and AR on EEG-revealed brain activity
      features for three typical brain behavior states (eyes-closed, eyes-open and
      music-listening). The analysis results revealed the following observations: (1)
      there is no significant difference in the alpha-wave-blocking effect during the
      eyes-open state compared with the eyes-closed state for both REST and AR
      references; (2) there was clear frontal EEG asymmetry during the resting state,
      and the degree of lateralization under REST was higher than that under AR; (3)
      the global brain functional connectivity density (FCD) and local FCD have higher
      values for REST than for AR under different behavior states; and (4) the value of
      the small-world network characteristic in the eyes-closed state is significantly
      (in full, alpha, beta and gamma frequency bands) higher than that in the eyes
      open state, and the small-world effect under the REST reference is higher than
      that under AR. In addition, the music-listening state has a higher small-world
      network effect than the eyes-closed state. The above results suggest that typical
      EEG features might be more clearly presented by applying the REST reference than
      by applying AR when using a 64-channel recording.

PMID- 29593491
TI  - Can Interactions Between alpha-Synuclein, Dopamine and Calcium Explain Selective
      Neurodegeneration in Parkinson's Disease?
AB  - Several lines of evidence place alpha-synuclein (aSyn) at the center of
      Parkinson's disease (PD) etiology, but it is still unclear why overexpression or
      mutated forms of this protein affect some neuronal populations more than others.
      Susceptible neuronal populations in PD, dopaminergic neurons of the substantia
      nigra pars compacta (SNpc) and the locus coeruleus (LC), are distinguished by
      relatively high cytoplasmic concentrations of dopamine and calcium ions. Here we
      review the evidence for the multi-hit hypothesis of neurodegeneration, including
      recent papers that demonstrate synergistic interactions between aSyn, calcium
      ions and dopamine that may lead to imbalanced protein turnover and selective
      susceptibility of these neurons. We conclude that decreasing the levels of any
      one of these toxicity mediators can be beneficial for the survival of SNpc and LC
      neurons, providing multiple opportunities for targeted drug interventions aimed
      at modifying the course of PD.

PMID- 29593492
TI  - Enteroviral Infection: The Forgotten Link to Amyotrophic Lateral Sclerosis?
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      that primarily attacks motor neurons in the brain and spinal cord, leading to
      progressive paralysis and ultimately death. Currently there is no effective
      therapy. The majority of ALS cases are sporadic, with no known family history;
      unfortunately the etiology remains largely unknown. Contribution of Enteroviruses
      (EVs), a family of positive-stranded RNA viruses including poliovirus,
      coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the
      development of ALS has been suspected as they can target motor neurons, and
      patients with prior poliomyelitis show a higher risk of motor neuron disease.
      Multiple efforts have been made to detect enteroviral genome in ALS patient
      tissues over the past two decades; however the clinical data are controversial
      and a causal relationship has not yet been established. Recent evidence from in
      vitro and animal studies suggests that enterovirus-induced pathology remarkably
      resembles the cellular and molecular phenotype of ALS, indicating a possible link
      between enteroviral infection and ALS pathogenesis. In this review, we summarize
      the nature of enteroviral infection, including route of infection, cells
      targeted, and viral persistence within the central nervous system (CNS). We
      review the molecular mechanisms underlying viral infection and highlight the
      similarity between viral pathogenesis and the molecular and pathological features
      of ALS, and finally, discuss the potential role of enteroviral infection in
      frontotemporal dementia (FTD), a disease that shares common clinical, genetic,
      and pathological features with ALS, and the significance of anti-viral therapy as
      an option for the treatment of ALS.

PMID- 29593493
TI  - Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation
      During Aging.
AB  - Rodent models of both aging and obesity are characterized by inflammation in
      specific brain regions, notably the corpus callosum, fornix, and hypothalamus.
      Microglia, the resident macrophages of the central nervous system, are important
      for brain development, neural support, and homeostasis. However, the effects of
      diet and lifestyle on microglia during aging are only partly understood. Here, we
      report alterations in microglia phenotype and functions in different brain
      regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and
      in response to voluntary running wheel exercise. We compared the expression
      levels of genes involved in immune response, phagocytosis, and metabolism in the
      hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune
      response of microglia from HFD or LFD mice to peripheral inflammation induced by
      intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated
      the effect of diet, physical exercise, and caloric restriction (40% reduction
      compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice.
      Changes in diet caused morphological changes in microglia, but did not change the
      microglia response to LPS-induced systemic inflammation. Expression of phagocytic
      markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter
      microglia of 24-month-old brain was markedly decreased in calorically restricted
      LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which
      might be an underlying mechanism for the protective role of caloric restriction
      during aging-associated decline.

PMID- 29593494
TI  - Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse
      Model of Acute Epilepsy.
AB  - Research on the antiepileptic effects of (endo-)cannabinoids has remarkably
      progressed in the years following the discovery of fundamental role of the
      endocannabinoid (eCB) system in controlling neural excitability. Moreover, an
      increasing number of well-documented cases of epilepsy patients exhibiting multi
      drug resistance report beneficial effects of cannabis use. Pre-clinical and
      clinical research has increasingly focused on the antiepileptic effectiveness of
      exogenous administration of cannabinoids and/or pharmacologically induced
      increase of eCBs such as anandamide (also known as arachidonoylethanolamide
      [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory
      processes and peripheral immunity to the onset and progression of epilepsy.
      Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2)
      was pursued as alternative therapeutic strategy for epilepsy.
      Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the
      centrally and peripherally present eCB AEA, and is a naturally occurring nutrient
      that has long been recognized for its analgesic and anti-inflammatory properties.
      Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in
      neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ),
      maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures.
      Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is
      devoid of addiction potential, dose limiting side effects and psychoactive
      effects, rendering PEA an appealing candidate as antiepileptic compound or
      adjuvant. In the present study, we aimed at assessing antiepileptic properties of
      PEA in a mouse model of acute epileptic seizures induced by systemic
      administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to
      resemble to different extents human temporal lobe epilepsy (TLE) depending on the
      route of KA administration; intracerebral (i.c.) injection was recently shown to
      most closely mimic human TLE, while systemic KA administration causes more
      widespread pathological damage, both in brain and periphery. To explore the
      potential of PEA to exert therapeutic effects both in brain and periphery, acute
      and subchronic administration of PEA by intraperitoneal (i.p.) injection was
      assessed on mice with systemically administered KA. Specifically, we
      investigated: (i) neuroprotective and anticonvulsant properties of acute and
      subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics
      of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post
      seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle
      injected mice. Finally, we compared the systemic PEA treatment with, and in
      combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH)
      in brain and periphery, in terms of anticonvulsant properties and modulation of
      eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA
      significantly alleviates seizure intensity, promotes neuroprotection and induces
      modulation of the plasma and hippocampal eCB and eiC levels in systemic KA
      injected mice.

PMID- 29593495
TI  - Mitochondrial Molecular Abnormalities Revealed by Proteomic Analysis of
      Hippocampal Organelles of Mice Triple Transgenic for Alzheimer Disease.
AB  - Mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's
      disease (AD). However, the precise mitochondrial molecular deficits in AD remain
      poorly understood. Mitochondrial and nuclear proteomic analysis in mature male
      triple transgenic AD mice (PS1M146V/APPSwe/TauP301L) by two-dimensional
      fluorescence difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF
      MS/MS, bio-informatics analysis and immunofluorescent staining were performed in
      this study. In addition to impaired spatial memory impairment and intracellular
      accumulation of amyloid 1-42 (Abeta1-42) in the 3xTg-AD mice, a well-accepted
      mouse model of the human disease, we also found significantly increased DNA
      oxidative damage in entorhinal cortex, hippocampal CA1, CA3 and dental gyrus
      (DG), as evidenced by the positive staining of 8-hydroxyguanosine, a biomarker of
      mild cognitive impairment early in AD. We identified significant differences in
      27 hippocampal mitochondrial proteins (11 increased and 16 decreased), and 37
      hippocampal nuclear proteins (12 increased and 25 decreased) in 3xTg-AD mice
      compared with the wild-type (WT) mice. Differentially expressed mitochondrial and
      nuclear proteins were mainly involved in energy metabolism (>55%), synapses, DNA
      damage, apoptosis and oxidative stress. Two proteins were differentially
      expressed in both hippocampal mitochondria and nuclei, namely electron transport
      chain (ETC)-related protein ATP synthase subunit d (ATP5H) was significantly
      decreased, and apoptosis-related dynamin-1 (DYN1), a pre-synaptic and
      mitochondrial division-regulated protein that was significantly increased. In
      sum, perturbations of hippocampus mitochondrial energy metabolism-related
      proteins responsible for ATP generation via oxidation phosphorylation (OXPHOS),
      especially nuclear-encoded OXPHOS proteins, correlated with the amyloid
      associated cognitive deficits of this murine AD model. The molecular changes in
      respiratory chain-related proteins and DYN1 may represent novel biomarkers of AD.

PMID- 29593496
TI  - Q-Rich Yeast Prion [PSI+] Accelerates Aggregation of Transthyretin, a Non-Q-Rich
      Human Protein.
AB  - Interactions amongst different amyloid proteins have been proposed as a probable
      mechanism of aggregation and thus an important risk factor for the onset as well
      as progression of various neurodegenerative disorders including Alzheimer's,
      Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis. Evidences suggest
      that transthyretin (TTR), a plasma protein associated with transthyretin
      amyloidosis or familial polyneuropathy (FAP) interacts with heterologous amyloid
      proteins including amyloid beta and islet amyloid polypeptide. In addition,
      recent clinical studies have revealed the presence of systemic polyneuropathy
      associated with FAP mutations in patients with spinocerebral ataxia, amyotrophic
      lateral sclerosis, and new familial systematic prion disease. Hence, it is
      important to investigate the interactions amongst different amyloid proteins to
      gain better insight into the pathology of amyloid disorders. Yeast has been an
      excellent model system to study interaction/ cross-seeding between heterologous
      amyloid proteins, more because of presence of endogenous yeast prions. Here, we
      examined interactions of non-glutamine (non-Q)-rich transthyretin, with glutamine
      (Q)-rich yeast prion protein Sup35. We established aggregation of an engineered
      double (F87M/L110M) mutant M-TTR-GFP in yeast. This mutant is monomeric and
      readily formed aggregates compared to WT-TTR-GFP in yeast at acidic pH.
      Interestingly, aggregation of M-TTR-GFP was significantly enhanced in presence of
      [PSI+], an endogenous prion form of Sup35. Different variants of [PSI+] seeded M
      TTR-GFP with different efficiencies and curing of [PSI+] (losing the prion form)
      in these strains reduced aggregation. Moreover, overexpression of prion domain of
      Sup35 fused to RFP (NM-RFP) also increased M-TTR-GFP aggregation. M-TTR-GFP and
      NM-RFP aggregates co-localized in perivacuolar and juxtranuclear region. Sup35
      protein was even immunocaptured in M-TTR-GFP aggregates. However, M-TTR-GFP
      overexpression did not induce Sup35 aggregation. Thus, it appears to be a
      unidirectional interaction between these two amyloid proteins. However, no affect
      on M-TTR-GFP aggregation was observed due to another yeast prion, [PIN+]. Our
      findings thus show the molecular interaction of transthyretin with yeast prion
      and support that sequence similarity is not the prime requirement for
      heterologous amyloid interactions.

PMID- 29593497
TI  - Reprogramming Glia Into Neurons in the Peripheral Auditory System as a Solution
      for Sensorineural Hearing Loss: Lessons From the Central Nervous System.
AB  - Disabling hearing loss affects over 5% of the world's population and impacts the
      lives of individuals from all age groups. Within the next three decades, the
      worldwide incidence of hearing impairment is expected to double. Since a leading
      cause of hearing loss is the degeneration of primary auditory neurons (PANs), the
      sensory neurons of the auditory system that receive input from mechanosensory
      hair cells in the cochlea, it may be possible to restore hearing by regenerating
      PANs. A direct reprogramming approach can be used to convert the resident spiral
      ganglion glial cells into induced neurons to restore hearing. This review
      summarizes recent advances in reprogramming glia in the CNS to suggest future
      steps for regenerating the peripheral auditory system. In the coming years,
      direct reprogramming of spiral ganglion glial cells has the potential to become
      one of the leading biological strategies to treat hearing impairment.

PMID- 29593498
TI  - Reactive Neuroblastosis in Huntington's Disease: A Putative Therapeutic Target
      for Striatal Regeneration in the Adult Brain.
AB  - The cellular and molecular mechanisms underlying the reciprocal relationship
      between adult neurogenesis, cognitive and motor functions have been an important
      focus of investigation in the establishment of effective neural replacement
      therapies for neurodegenerative disorders. While neuronal loss, reactive gliosis
      and defects in the self-repair capacity have extensively been characterized in
      neurodegenerative disorders, the transient excess production of neuroblasts
      detected in the adult striatum of animal models of Huntington's disease (HD) and
      in post-mortem brain of HD patients, has only marginally been addressed. This
      abnormal cellular response in the striatum appears to originate from the
      selective proliferation and ectopic migration of neuroblasts derived from the
      subventricular zone (SVZ). Based on and in line with the term "reactive
      astrogliosis", we propose to name the observed cellular event "reactive
      neuroblastosis". Although, the functional relevance of reactive neuroblastosis is
      unknown, we speculate that this process may provide support for the tissue
      regeneration in compensating the structural and physiological functions of the
      striatum in lieu of aging or of the neurodegenerative process. Thus, in this
      review article, we comprehend different possibilities for the regulation of
      striatal neurogenesis, neuroblastosis and their functional relevance in the
      context of HD.

PMID- 29593499
TI  - Mob2 Insufficiency Disrupts Neuronal Migration in the Developing Cortex.
AB  - Disorders of neuronal mispositioning during brain development are phenotypically
      heterogeneous and their genetic causes remain largely unknown. Here, we report
      biallelic variants in a Hippo signaling factor-MOB2-in a patient with one such
      disorder, periventricular nodular heterotopia (PH). Genetic and cellular analysis
      of both variants confirmed them to be loss-of-function with enhanced sensitivity
      to transcript degradation via nonsense mediated decay (NMD) or increased protein
      turnover via the proteasome. Knockdown of Mob2 within the developing mouse cortex
      demonstrated its role in neuronal positioning. Cilia positioning and number
      within migrating neurons was also impaired with comparable defects detected
      following a reduction in levels of an upstream modulator of Mob2 function, Dchs1,
      a previously identified locus associated with PH. Moreover, reduced Mob2
      expression increased phosphorylation of Filamin A, an actin cross-linking protein
      frequently mutated in cases of this disorder. These results reveal a key role for
      Mob2 in correct neuronal positioning within the developing cortex and outline a
      new candidate locus for PH development.

PMID- 29593501
TI  - Chronic Stress Reduces Nectin-1 mRNA Levels and Disrupts Dendritic Spine
      Plasticity in the Adult Mouse Perirhinal Cortex.
AB  - In adulthood, chronic exposure to stressful experiences disrupts synaptic
      plasticity and cognitive function. Previous studies have shown that perirhinal
      cortex-dependent object recognition memory is impaired by chronic stress.
      However, the stress effects on molecular expression and structural plasticity in
      the perirhinal cortex remain unclear. In this study, we applied the chronic
      social defeat stress (CSDS) paradigm and measured the mRNA levels of nectin-1,
      nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs) implicated
      in the adverse stress effects, in the perirhinal cortex of wild-type (WT) and
      conditional forebrain corticotropin-releasing hormone receptor 1 conditional
      knockout (CRHR1-CKO) mice. Chronic stress reduced perirhinal nectin-1 mRNA levels
      in WT but not CRHR1-CKO mice. In conditional forebrain corticotropin-releasing
      hormone conditional overexpression (CRH-COE) mice, perirhinal nectin-1 mRNA
      levels were also reduced, indicating that chronic stress modulates nectin-1
      expression through the CRH-CRHR1 system. Moreover, chronic stress altered
      dendritic spine morphology in the main apical dendrites and reduced spine density
      in the oblique apical dendrites of perirhinal layer V pyramidal neurons. Our data
      suggest that chronic stress disrupts cell adhesion and dendritic spine plasticity
      in perirhinal neurons, which may contribute to stress-induced impairments of
      perirhinal cortex-dependent memory.

PMID- 29593502
TI  - The Spinal Neurons Exhibit an ON-OFF and OFF-ON Firing Activity Around the Onset
      of Fictive Scratching Episodes in the Cat.
AB  - In a previous report, we found neurons with ON-OFF and OFF-ON firing activity in
      the obex reticular formation during scratching. The aim of the present study was
      to examine whether the spinal neurons also exhibit this type of activity in
      relation to the "postural stage" of fictive scratching in the cat. We found that
      the extensor and intermediate scratching neurons exhibit an ON-OFF firing rate;
      conversely, the flexor neurons show an OFF-ON activity, relative to every
      scratching episode. These patterns of spiking activity are similar to those found
      in neurons from the obex reticular formation during scratching. Our findings
      provide support to the following hypotheses. First, there is a possible
      functional link between supraspinal and spinal, ON-OFF and OFF-ON neuronal
      groups. Second, the fictive goal-directed motor action to maintain the fictive
      "postural stage" of the hindlimb during fictive scratching is associated with the
      neuronal tonic activity of the OFF-ON spinal neurons, whereas the ON-OFF spinal
      neurons are associated with an extensor tone that occurred prior the postural
      stage.

PMID- 29593500
TI  - Sensing Exocytosis and Triggering Endocytosis at Synapses: Synaptic Vesicle
      Exocytosis-Endocytosis Coupling.
AB  - The intact synaptic structure is critical for information processing in neural
      circuits. During synaptic transmission, rapid vesicle exocytosis increases the
      size of never terminals and endocytosis counteracts the increase. Accumulating
      evidence suggests that SV exocytosis and endocytosis are tightly connected in
      time and space during SV recycling, and this process is essential for synaptic
      function and structural stability. Research in the past has illustrated the
      molecular details of synaptic vesicle (SV) exocytosis and endocytosis; however,
      the mechanisms that timely connect these two fundamental events are poorly
      understood at central synapses. Here we discuss recent progress in SV recycling
      and summarize several emerging mechanisms by which synapses can "sense" the
      occurrence of exocytosis and timely initiate compensatory endocytosis. They
      include Ca2+ sensing, SV proteins sensing, and local membrane stress sensing. In
      addition, the spatial organization of endocytic zones adjacent to active zones
      provides a structural basis for efficient coupling between SV exocytosis and
      endocytosis. Through linking different endocytosis pathways with SV fusion, these
      mechanisms ensure necessary plasticity and robustness of nerve terminals to meet
      diverse physiological needs.

PMID- 29593503
TI  - Emergence of Serotonergic Neurons After Spinal Cord Injury in Turtles.
AB  - Plasticity of neural circuits takes many forms and plays a fundamental role in
      regulating behavior to changing demands while maintaining stability. For example,
      during spinal cord development neurotransmitter identity in neurons is
      dynamically adjusted in response to changes in the activity of spinal networks.
      It is reasonable to speculate that this type of plasticity might occur also in
      mature spinal circuits in response to injury. Because serotonergic signaling has
      a central role in spinal cord functions, we hypothesized that spinal cord injury
      (SCI) in the fresh water turtle Trachemys scripta elegans may trigger homeostatic
      changes in serotonergic innervation. To test this possibility we performed
      immunohistochemistry for serotonin (5-HT) and key molecules involved in the
      determination of the serotonergic phenotype before and after SCI. We found that
      as expected, in the acute phase after injury the dense serotonergic innervation
      was strongly reduced. However, 30 days after SCI the population of serotonergic
      cells (5-HT+) increased in segments caudal to the lesion site. These cells
      expressed the neuronal marker HuC/D and the transcription factor Nkx6.1. The new
      serotonergic neurons did not incorporate the thymidine analog 5-bromo-2'
      deoxyuridine (BrdU) and did not express the proliferating cell nuclear antigen
      (PCNA) indicating that novel serotonergic neurons were not newborn but post
      mitotic cells that have changed their neurochemical identity. Switching towards a
      serotonergic neurotransmitter phenotype may be a spinal cord homeostatic
      mechanism to compensate for the loss of descending serotonergic neuromodulation,
      thereby helping the outstanding functional recovery displayed by turtles. The 5
      HT1A receptor agonist (+/-)-8-Hydroxy-2-dipropylaminotetralin hydrobromide (8-OH
      DPAT) blocked the increase in 5-HT+ cells suggesting 5-HT1A receptors may trigger
      the respecification process.

PMID- 29593504
TI  - Neuromodulatory Correlates of Pupil Dilation.
AB  - Pupillometry has long been used as a measure of brain state. Changes in pupil
      diameter are thought to coincide with the activity of neuromodulators, including
      noradrenaline and acetylcholine, producing alterations in the brain state and
      corresponding changes in behavior. Here we review mechanisms underlying the
      control of pupil diameter and how these mechanisms are correlated with changes in
      cortical activity and the recruitment of neuromodulatory circuits.

PMID- 29593505
TI  - The Shark Basal Hypothalamus: Molecular Prosomeric Subdivisions and Evolutionary
      Trends.
AB  - The hypothalamus is a key integrative center of the vertebrate brain. To better
      understand its ancestral morphological organization and evolution, we previously
      analyzed the segmental organization of alar subdivisions in the catshark
      Scyliorhinus canicula, a cartilaginous fish and thus a basal representative of
      gnathostomes (jawed vertebrates). With the same aim, we deepen here in the
      segmental organization of the catshark basal hypothalamus by revisiting previous
      data on ScOtp, ScDlx2/5, ScNkx2.1, ScShh expression and Shh immunoreactivity
      jointly with new data on ScLhx5, ScEmx2, ScLmx1b, ScPitx2, ScPitx3a, ScFoxa1,
      ScFoxa2 and ScNeurog2 expression and proliferating cell nuclear antigen (PCNA)
      immunoreactivity. Our study reveals a complex genoarchitecture for chondrichthyan
      basal hypothalamus on which a total of 21 microdomains were identified. Six
      belong to the basal acroterminal region, the rostral-most point of the basal
      neural tube; seven are described in the tuberal region (Tu/RTu); four in the
      perimamillar region (PM/PRM) and four in the mamillar one (MM/RM). Interestingly,
      the same set of genes does not necessarily describe the same microdomains in
      mice, which in part contributes to explain how forebrain diversity is achieved.
      This study stresses the importance of analyzing data from basal vertebrates to
      better understand forebrain diversity and hypothalamic evolution.

PMID- 29593507
TI  - The Times of Our Lives: Interaction Among Different Biological Periodicities.
AB  - Environmental cycles on Earth display different periodicities, including daily,
      tidal or annual time scales. Virtually all living organisms have developed
      temporal mechanisms to adapt to such changes in environmental conditions. These
      biological timing structures-ranging from microsecond to seasonal timing-may have
      intrinsic properties and even different clock machinery. However, interaction
      among these temporal systems may present evolutionary advantages, for example,
      when species are exposed to changing climatic conditions or different geographic
      locations. Here, we present and discuss a model that accounts for the circadian
      regulation of both ultradian (less than 24-h) and infradian (more than 24-h)
      cycles and for the interaction among the three time scales. We show two clear
      examples of such interaction: (i) between the circadian clock and the seasonal
      regulation of the Hypothalamic-Pituitary-Thyroid (HPT) axis; and (ii) between the
      circadian clock and the hypothalamic-nigrostriatal (HNS) ultradian modulation.
      This remarkable interplay among the otherwise considered isolated rhythms has
      been demonstrated to exist in diverse organisms, suggesting an adaptive advantage
      of multiple scales of biological timing.

PMID- 29593506
TI  - The Interaction of Pre-programmed Eye Movements With the Vestibulo-Ocular Reflex.
AB  - The Vestibulo-Ocular Reflex (VOR) works to stabilize gaze during unexpected head
      movements. However, even subjects who lack a VOR (e.g., vestibulopathic patients)
      can achieve gaze stability during planned head movements by using pre-programmed
      eye movements (PPEM). The extent to which PPEM are used by healthy intact
      subjects and how they interact with the VOR is still unclear. We propose a model
      of gaze stabilization which makes several claims: (1) the VOR provides ocular
      stability during unexpected (i.e., passive) head movements; (2) PPEM are used by
      both healthy and vestibulopathic subjects during planned (i.e., active) head
      movements; and (3) when a passive perturbation interrupts an active head movement
      in intact animals (i.e., combined passive and active head movement) the VOR works
      with PPEM to provide compensation. First, we show how our model can reconcile
      some seemingly conflicting findings in earlier literature. We then test the above
      mentioned predictions against data we collected from both healthy and vestibular
      lesioned guinea pigs. We found that (1) vestibular-lesioned animals showed a
      dramatic decrease in compensatory eye movements during passive head movements,
      (2) both populations showed improved ocular compensation during active vs.
      passive head movements, and (3) during combined active and passive head
      movements, eye movements compensated for both the active and passive component of
      head velocity. These results support our hypothesis that while the VOR provides
      compensation during passive head movements, PPEM are used by both intact and
      lesioned subjects during active movements and further, that PPEM work together
      with the VOR to achieve gaze stability.

PMID- 29593508
TI  - GABAergic Control of Nigrostriatal and Mesolimbic Dopamine in the Rat Brain.
AB  - Purpose: The present study assessed the effects of the GABAA receptor (R) agonist
      muscimol (MUS), and the GABAAR antagonist bicuculline (BIC) on neocortical and
      subcortical radioligand binding to dopamine D2/3Rs in relation to motor and
      exploratory behaviors in the rat. Methods: D2/3R binding was measured with small
      animal SPECT in baseline and after challenge with either 1 mg/kg MUS or 1 mg/kg
      BIC, using [123I]IBZM as radioligand. Motor/exploratory behaviors were assessed
      for 30 min in an open field prior to radioligand administration. Anatomical
      information was gained with a dedicated small animal MRI tomograph. Based on the
      Paxinos rat brain atlas, regions of interest were defined on SPECT-MRI overlays.
      Estimations of the binding potentials in baseline and after challenges were
      obtained by computing ratios of the specifically bound compartments to the
      cerebellar reference region. Results: After MUS, D2/3R binding was significantly
      reduced in caudateputamen, nucleus accumbens, thalamus, substania nigra/ventral
      tegmental area, and posterior hippocampus relative to baseline (0.005 <= p <=
      0.012). In all these areas, except for the thalamus, D2/3R binding was negatively
      correlated with grooming in the first half and positively correlated with various
      motor/exploratory behaviors in the second half of the testing session. After BIC,
      D2/3R binding was significantly elevated in caudateputamen (p = 0.022) and
      thalamus (p = 0.047) relative to baseline. D2/3R binding in caudateputamen and
      thalamus was correlated negatively with sitting duration and sitting frequency
      and positively with motor/exploratory behaviors in the first half of the testing
      time. Conclusions: Findings indicate direct GABAergic control over nigrostriatal
      and mesolimbic dopamine levels in relation to behavioral action. This may be of
      relevance for neuropsychiatric conditions such as anxiety disorder and
      schizophrenia, which are characterized by both dopaminergic and GABAergic
      dysfunction.

PMID- 29593509
TI  - Tantrums, Emotion Reactions and Their EEG Correlates in Childhood Benign Rolandic
      Epilepsy vs. Complex Partial Seizures: Exploratory Observations.
AB  - We explored associations between EEG pathophysiology and emotional/behavioral
      (E/B) problems of children with two types of epilepsy using standard parent
      questionnaires and two new indicators: tantrums recorded by parents at home and
      brief, emotion-eliciting situations in the laboratory. Children with Benign
      Rolandic epilepsy (BRE, N = 6) reportedly had shorter, more angry tantrums from
      which they recovered quickly. Children with Complex Partial Seizures (CPS, N =
      13) had longer, sadder tantrums often followed by bad moods. More generally, BRE
      correlated with anger and aggression; CPS with sadness and withdrawal. Scores of
      a composite group of siblings (N = 11) were generally intermediate between the
      BRE and CPS groups. Across all children, high voltage theta and/or interictal
      epileptiform discharges (IEDs) correlated with negative emotional reactions. Such
      EEG abnormalities in left hemisphere correlated with greater social fear, right
      hemisphere EEG abnormalities with greater anger. Right hemisphere localization in
      CPS was also associated with parent-reported problems at home. If epilepsy alters
      neural circuitry thereby increasing negative emotions, additional assessment of
      anti-epileptic drug treatment of epilepsy-related E/B problems would be
      warranted.

PMID- 29593510
TI  - Chronic Stress Alters Behavior in the Forced Swim Test and Underlying Neural
      Activity in Animals Exposed to Alcohol Prenatally: Sex- and Time-Dependent
      Effects.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) stress response has
      been suggested to play a role in vulnerability to stress-related disorders, such
      as depression. Prenatal alcohol exposure (PAE) may result in HPA dysregulation,
      which in turn may predispose individuals to the effects of stress exposure
      throughout life, and increase their risk of developing depression compared to
      unexposed individuals. We examined the immediate and delayed effects of chronic
      unpredictable stress (CUS) in adulthood on behavior of PAE animals in the forced
      swim test (FST) and the neurocircuitry underlying behavioral, emotional, and
      stress regulation. Adult male and female offspring from PAE and control
      conditions were tested for 2 days in the FST, with testing initiated either 1 day
      (CUS-1; immediate) or 14 days (CUS-14; delayed) post-CUS. Following testing, c
      fos mRNA expression of the medial prefrontal cortex (mPFC), amygdala, hippocampal
      formation, and the paraventricular nucleus of the hypothalamus was assessed. Our
      results indicate that PAE and CUS interact to differentially alter FST behaviors
      and neural activation of several brain areas in males and females, and effects
      may depend on whether testing is immediate or delayed post-CUS. PAE males showed
      decreased time immobile (Day 1 of FST) following immediate testing, while PAE
      females showed increased time immobile (Day 2 of FST) following delayed testing
      compared to their respective control counterparts. Moreover, in males, PAE
      decreased c-fos mRNA expression in the lateral and central nuclei of the amygdala
      in the non-CUS condition, and increased c-fos mRNA expression in the CA1 in the
      CUS-14 condition. By contrast in females, c-fos mRNA expression in the Cg1 was
      decreased in PAE animals (independent of CUS) and decreased in all mPFC
      subregions in CUS-14 animals (independent of prenatal treatment). Constrained
      principal component analysis, used to identify neural and behavioral networks,
      revealed that PAE altered the activation of these networks and modulated the
      effects of CUS on these networks in a sex- and time-dependent manner. This
      dysregulation of the neurocircuitry underlying behavioral, emotional and stress
      regulation, may ultimately contribute to an increased vulnerability to
      psychopathologies, such as depression, that are often observed following PAE.

PMID- 29593512
TI  - Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional
      MRI.
AB  - Purpose: Presbycusis, age-related hearing loss, is believed to involve neural
      changes in the central nervous system, which is associated with an increased risk
      of cognitive impairment. The goal of this study was to determine if presbycusis
      disrupted spontaneous neural activity in specific brain areas involved in
      auditory processing, attention and cognitive function using resting-state
      functional magnetic resonance imaging (fMRI) approach. Methods: Hearing and
      resting-state fMRI measurements were obtained from 22 presbycusis patients and 23
      age-, sex- and education-matched healthy controls. To identify changes in
      spontaneous neural activity associated with age-related hearing loss, we compared
      the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity
      (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined
      if these changes were linked to clinical measures of presbycusis. Results:
      Compared with healthy controls, presbycusis patients manifested decreased
      spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal
      gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased
      neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus
      (PoCG). A significant negative correlation was observed between ALFF/ReHo
      activity in the STG and average hearing thresholds in presbycusis patients.
      Increased ALFF/ReHo activity in the MFG was positively correlated with impaired
      Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function
      involving the frontal lobe. Conclusions: Presbycusis patients have disrupted
      spontaneous neural activity reflected by ALFF and ReHo measurements in several
      brain regions; these changes are associated with specific cognitive performance
      and speech/language processing. These findings mainly emphasize the crucial role
      of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will
      lead to a better understanding of the neuropathological mechanisms underlying
      presbycusis.

PMID- 29593513
TI  - Zebrafish Lacking Circadian Gene per2 Exhibit Visual Function Deficiency.
AB  - The retina has an intrinsic circadian clock, but the importance of this clock for
      vision is unknown. Zebrafish offer many advantages for studying vertebrate vision
      and circadian rhythm. Here, we explored the role of zebrafish per2, a light
      regulated gene, in visual behavior and the underlying mechanisms. We observed
      that per2 mutant zebrafish larvae showed decreased contrast sensitivity and
      visual acuity using optokinetic response (OKR) assays. Using a visual motor
      response (VMR) assay, we observed normal OFF responses but abnormal ON responses
      in mutant zebrafish larvae. Immunofluorescence showed that mutants had a normal
      morphology of cone photoreceptor cells and retinal organization. However,
      electron microscopy showed that per2 mutants displayed abnormal and decreased
      photoreceptor ribbon synapses with arciform density, which resulted in retinal ON
      pathway defect. We also examined the expression of three cone opsins by
      quantitative real-time PCR (qRT-PCR), and the expression of long-wave-sensitive
      opsin (opn1lw) and short-wave-sensitive opsin (opn1sw) was reduced in mutant
      zebrafish larvae. qRT-PCR analyses also showed a down-regulation of the clock
      genes cry1ba and bmal1b in the adult eye of per2 mutant zebrafish. This study
      identified a mechanism by which a clock gene affects visual function and defined
      important roles of per2 in retinal information processing.

PMID- 29593514
TI  - Lie Detection Using fNIRS Monitoring of Inhibition-Related Brain Regions
      Discriminates Infrequent but not Frequent Liars.
AB  - Functional near-infrared spectroscopy (fNIRS) was used to test whether monitoring
      inhibition-related brain regions is a feasible method for detecting both
      infrequent liars and frequent liars. Thirty-two participants were divided into
      two groups: the deceptive group (liars) and the non-deceptive group (ND group,
      innocents). All the participants were required to undergo a simulated
      interrogation by a computer. The participants from the deceptive group were
      instructed to tell a mix of lies and truths and those of the ND group were
      instructed always to tell the truth. Based on the number of deceptions, the
      participants of the deceptive group were further divided into a infrequently
      deceptive group (IFD group, infrequent liars) and a frequently deceptive group
      (FD group, frequent liars). The infrequent liars exhibited greater neural
      activities than the frequent liars and the innocents in the left middle frontal
      gyrus (MFG) when performing the deception detection tasks. While performing
      deception detection tasks, infrequent liars showed significantly greater neural
      activation in the left MFG than the baseline, but frequent liars and innocents
      did not exhibit this pattern of neural activation in any area of inhibition
      related brain regions. The results of individual analysis showed an acceptable
      accuracy of detecting infrequent liars, but an unacceptable accuracy of detecting
      frequent liars. These results suggest that using fNIRS monitoring of inhibition
      related brain regions is feasible for detecting infrequent liars, for whom
      deception may be more effortful and therefore more physiologically marked, but
      not frequent liars.

PMID- 29593515
TI  - Resting-State Brain Signal Variability in Prefrontal Cortex Is Associated With
      ADHD Symptom Severity in Children.
AB  - Atypical brain function in attention-deficit/hyperactivity disorder (ADHD) has
      been identified using both task-activation and functional connectivity fMRI
      approaches. Recent work highlights the potential for another measure derived from
      functional neuroimaging data, brain signal variability, to reveal insights into
      clinical conditions. Higher brain signal variability has previously been linked
      with optimal behavioral performance. At present, little is known regarding the
      relationship between resting-state brain signal variability and ADHD symptom
      severity. The current study examined the relationship between a measure of moment
      to-moment brain signal variability called mean-square successive difference
      (MSSD) and ADHD symptomatology in a group of children (7-12 years old) with (n =
      40) and without (n = 30) a formal diagnosis of ADHD. A categorical analysis
      comparing subjects with and without a clinical diagnosis of ADHD showed no
      differences in MSSD between groups. A dimensional analysis revealed a positive
      relationship between MSSD and overall ADHD symptom severity and inattention
      across children with and without an ADHD diagnosis. Specifically, this positive
      relationship was found in medial prefrontal areas comprising the default mode
      network. These results demonstrate a link between intrinsic brain signal
      variability and ADHD symptom severity that cuts across diagnostic categories, and
      point to a locus of dysfunction consistent with previous neuroimaging literature.

PMID- 29593511
TI  - Noradrenergic Modulation of Fear Conditioning and Extinction.
AB  - The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning
      and memory. Here we begin with an overview of the LC-NE system. We then consider
      how both direct and indirect manipulations of the LC-NE system affect cued and
      contextual aversive learning and memory. We propose that NE dynamically modulates
      Pavlovian conditioning and extinction, either promoting or impairing learning
      aversive processes under different levels of behavioral arousal. We suggest that
      under high levels of stress (e.g., during/soon after fear conditioning) the locus
      coeruleus (LC) promotes cued fear learning by enhancing amygdala function while
      simultaneously blunting prefrontal function. Under low levels of arousal, the LC
      promotes PFC function to promote downstream inhibition of the amygdala and foster
      the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex
      (mPFC) might be described by an inverted-U function such that it can either
      enhance or hinder learning depending on arousal states. In addition, LC-NE seems
      to be particularly important for the acquisition, consolidation and extinction of
      contextual fear memories. This may be due to dense adrenoceptor expression in the
      hippocampus (HPC) which encodes contextual information, and the ability of NE to
      regulate long-term potentiation (LTP). Moreover, recent work reveals that the
      diversity of LC-NE functions in aversive learning and memory are mediated by
      functionally heterogeneous populations of LC neurons that are defined by their
      projection targets. Hence, LC-NE function in learning and memory is determined by
      projection-specific neuromodulation that accompanies various states of behavioral
      arousal.

PMID- 29593516
TI  - Online Adaptation to Altered Auditory Feedback Is Predicted by Auditory Acuity
      and Not by Domain-General Executive Control Resources.
AB  - When a speaker's auditory feedback is altered, he adapts for the perturbation by
      altering his own production, which demonstrates the role of auditory feedback in
      speech motor control. In the present study, we explored the role of auditory
      acuity and executive control in this process. Based on the DIVA model and the
      major cognitive control models, we expected that higher auditory acuity, and
      better executive control skills would predict larger adaptation to the
      alteration. Thirty-six Spanish native speakers performed an altered auditory
      feedback experiment, executive control (numerical Stroop, Simon and Flanker)
      tasks, and auditory acuity tasks (loudness, pitch, and melody pattern
      discrimination). In the altered feedback experiment, participants had to produce
      the pseudoword "pep" (/pep/) while perceiving their auditory feedback in real
      time through earphones. The auditory feedback was first unaltered and then
      progressively altered in F1 and F2 dimensions until maximal alteration (F1 -150
      Hz; F2 +300 Hz). The normalized distance of maximal adaptation ranged from 4 to
      137 Hz (median of 75 +/- 36). The different measures of auditory acuity were
      significant predictors of adaptation, while individual measures of cognitive
      function skills (obtained from the executive control tasks) were not. Better
      auditory discriminators adapted more to the alteration. We conclude that
      adaptation to altered auditory feedback is very well-predicted by general
      auditory acuity, as suggested by the DIVA model. In line with the framework of
      motor-control models, no specific claim on the implication of executive resources
      in speech motor control can be made.

PMID- 29593517
TI  - Emotional Prosody Processing in Epilepsy: Some Insights on Brain Reorganization.
AB  - Drug resistant epilepsy is one of the most complex, multifactorial and polygenic
      neurological syndrome. Besides its dynamicity and variability, it still provides
      us with a model to study brain-behavior relationship, giving cues on the anatomy
      and functional representation of brain function. Given that onset zone of focal
      epileptic seizures often affects different anatomical areas, cortical but limited
      to one hemisphere, this condition also let us study the functional differences of
      the left and right cerebral hemispheres. One lateralized function in the human
      brain is emotional prosody, and it can be a useful ictal sign offering hints on
      the location of the epileptogenic zone. Besides its importance for effective
      communication, prosody is not considered an eloquent domain, making resective
      surgery on its neural correlates feasible. We performed an Electronic databases
      search (Medline and PsychINFO) from inception to July 2017 for studies about
      prosody in epilepsy. The search terms included "epilepsy," "seizure," "emotional
      prosody," and "vocal affect." This review focus on emotional prosody processing
      in epilepsy as it can give hints regarding plastic functional changes following
      seizures (preoperatively), resection (post operatively), and also as an ictal
      sign enabling the assessment of dynamic brain networks. Moreover, it is argued
      that such reorganization can help to preserve the expression and reception of
      emotional prosody as a central skill to develop appropriate social interactions.

PMID- 29593518
TI  - Task-Relevant Information Modulates Primary Motor Cortex Activity Before Movement
      Onset.
AB  - Monkey neurophysiology research supports the affordance competition hypothesis
      (ACH) proposing that cognitive information useful for action selection is
      integrated in sensorimotor areas. In this view, action selection would emerge
      from the simultaneous representation of competing action plans, in parallel
      biased by relevant task factors. This biased competition would take place up to
      primary motor cortex (M1). Although ACH is plausible in environments affording
      choices between actions, its relevance for human decision making is less clear.
      To address this issue, we designed an functional magnetic resonance imaging
      (fMRI) experiment modeled after monkey neurophysiology studies in which human
      participants processed cues conveying predictive information about upcoming
      button presses. Our results demonstrate that, as predicted by the ACH, predictive
      information (i.e., the relevant task factor) biases activity of primary motor
      regions. Specifically, first, activity before movement onset in contralateral M1
      increases as the competition is biased in favor of a specific button press
      relative to activity in ipsilateral M1. Second, motor regions were more tightly
      coupled with fronto-parietal regions when competition between potential actions
      was high, again suggesting that motor regions are also part of the biased
      competition network. Our findings support the idea that action planning dynamics
      as proposed in the ACH are valid both in human and non-human primates.

PMID- 29593519
TI  - Evolving Simple Models of Diverse Intrinsic Dynamics in Hippocampal Neuron Types.
AB  - The diversity of intrinsic dynamics observed in neurons may enhance the
      computations implemented in the circuit by enriching network-level emergent
      properties such as synchronization and phase locking. Large-scale spiking network
      models of entire brain regions offer a platform to test theories of neural
      computation and cognitive function, providing useful insights on information
      processing in the nervous system. However, a systematic in-depth investigation
      requires network simulations to capture the biological intrinsic diversity of
      individual neurons at a sufficient level of accuracy. The computationally
      efficient Izhikevich model can reproduce a wide range of neuronal behaviors
      qualitatively. Previous studies using optimization techniques, however, were less
      successful in quantitatively matching experimentally recorded voltage traces. In
      this article, we present an automated pipeline based on evolutionary algorithms
      to quantitatively reproduce features of various classes of neuronal spike
      patterns using the Izhikevich model. Employing experimental data from
      Hippocampome.org, a comprehensive knowledgebase of neuron types in the rodent
      hippocampus, we demonstrate that our approach reliably fit Izhikevich models to
      nine distinct classes of experimentally recorded spike patterns, including
      delayed spiking, spiking with adaptation, stuttering, and bursting. Importantly,
      by leveraging the parameter-exploration capabilities of evolutionary algorithms,
      and by representing qualitative spike pattern class definitions in the error
      landscape, our approach creates several suitable models for each neuron type,
      exhibiting appropriate feature variabilities among neurons. Moreover, we
      demonstrate the flexibility of our methodology by creating multi-compartment
      Izhikevich models for each neuron type in addition to single-point versions.
      Although the results presented here focus on hippocampal neuron types, the same
      strategy is broadly applicable to any neural systems.

PMID- 29593521
TI  - Hierarchical Spatial Concept Formation Based on Multimodal Information for Human
      Support Robots.
AB  - In this paper, we propose a hierarchical spatial concept formation method based
      on the Bayesian generative model with multimodal information e.g., vision,
      position and word information. Since humans have the ability to select an
      appropriate level of abstraction according to the situation and describe their
      position linguistically, e.g., "I am in my home" and "I am in front of the
      table," a hierarchical structure of spatial concepts is necessary in order for
      human support robots to communicate smoothly with users. The proposed method
      enables a robot to form hierarchical spatial concepts by categorizing multimodal
      information using hierarchical multimodal latent Dirichlet allocation (hMLDA).
      Object recognition results using convolutional neural network (CNN), hierarchical
      k-means clustering result of self-position estimated by Monte Carlo localization
      (MCL), and a set of location names are used, respectively, as features in vision,
      position, and word information. Experiments in forming hierarchical spatial
      concepts and evaluating how the proposed method can predict unobserved location
      names and position categories are performed using a robot in the real world.
      Results verify that, relative to comparable baseline methods, the proposed method
      enables a robot to predict location names and position categories closer to
      predictions made by humans. As an application example of the proposed method in a
      home environment, a demonstration in which a human support robot moves to an
      instructed place based on human speech instructions is achieved based on the
      formed hierarchical spatial concept.

PMID- 29593520
TI  - IClinfMRI Software for Integrating Functional MRI Techniques in Presurgical
      Mapping and Clinical Studies.
AB  - Task-evoked and resting-state (rs) functional magnetic resonance imaging (fMRI)
      techniques have been applied to the clinical management of neurological diseases,
      exemplified by presurgical localization of eloquent cortex, to assist
      neurosurgeons in maximizing resection while preserving brain functions. In
      addition, recent studies have recommended incorporating cerebrovascular
      reactivity (CVR) imaging into clinical fMRI to evaluate the risk of lesion
      induced neurovascular uncoupling (NVU). Although each of these imaging techniques
      possesses its own advantage for presurgical mapping, a specialized clinical
      software that integrates the three complementary techniques and promptly outputs
      the analyzed results to radiology and surgical navigation systems in a clinical
      format is still lacking. We developed the Integrated fMRI for Clinical Research
      (IClinfMRI) software to facilitate these needs. Beyond the independent processing
      of task-fMRI, rs-fMRI, and CVR mapping, IClinfMRI encompasses three unique
      functions: (1) supporting the interactive rs-fMRI mapping while visualizing task
      fMRI results (or results from published meta-analysis) as a guidance map, (2)
      indicating/visualizing the NVU potential on analyzed fMRI maps, and (3) exporting
      these advanced mapping results in a Digital Imaging and Communications in
      Medicine (DICOM) format that are ready to export to a picture archiving and
      communication system (PACS) and a surgical navigation system. In summary,
      IClinfMRI has the merits of efficiently translating and integrating state-of-the
      art imaging techniques for presurgical functional mapping and clinical fMRI
      studies.

PMID- 29593522
TI  - Frontoparietal tDCS Benefits Visual Working Memory in Older Adults With Low
      Working Memory Capacity.
AB  - Working memory (WM) permits maintenance of information over brief delays and is
      an essential executive function. Unfortunately, WM is subject to age-related
      decline. Some evidence supports the use of transcranial direct current
      stimulation (tDCS) to improve visual WM. A gap in knowledge is an understanding
      of the mechanism characterizing these tDCS linked effects. To address this gap,
      we compared the effects of two tDCS montages designed on visual working memory
      (VWM) performance. The bifrontal montage was designed to stimulate the heightened
      bilateral frontal activity observed in aging adults. The unilateral
      frontoparietal montage was designed to stimulate activation patterns observed in
      young adults. Participants completed three sessions (bilateral frontal, right
      frontoparietal, sham) of anodal tDCS (20 min, 2 mA). During stimulation,
      participants performed a visual long-term memory (LTM) control task and a visual
      WM task. There was no effect of tDCS on the LTM task. Participants receiving
      right unilateral tDCS showed a WM benefit. This pattern was most robust in older
      adults with low WM capacity. To address the concern that the key difference
      between the two tDCS montages could be tDCS over the posterior parietal cortex
      (PPC), we included new analyses from a previous study applying tDCS targeting the
      PPC paired with a recognition VWM task. No significant main effects were found. A
      subsequent experiment in young adults found no significant effect of either tDCS
      montage on either task. These data indicate that tDCS montage, age and WM
      capacity should be considered when designing tDCS protocols. We interpret these
      findings as suggestive that protocols designed to restore more youthful patterns
      of brain activity are superior to those that compensate for age-related changes.

PMID- 29593523
TI  - Functional Hemispheric (A)symmetries in the Aged Brain-Relevance for Working
      Memory.
AB  - Functional hemispheric asymmetries have been described in different cognitive
      processes, such as decision-making and motivation. Variations in the pattern of
      left/right activity have been associated with normal brain functioning, and with
      neuropsychiatric diseases. Such asymmetries in brain activity evolve throughout
      life and are thought to decrease with aging, but clear associations with
      cognitive function have never been established. Herein, we assessed functional
      laterality during a working memory task (N-Back) in a healthy aging cohort (over
      50 years old) and associated these asymmetries with performance in the test.
      Activity of lobule VI of the cerebellar hemisphere and angular gyrus was found to
      be lateralized to the right hemisphere, while the precentral gyrus presented left
      > right activation during this task. Interestingly, 1-Back accuracy was
      positively correlated with left > right superior parietal lobule activation,
      which was mostly due to the influence of the left hemisphere. In conclusion,
      although regions were mostly symmetrically activated during the N-Back task,
      performance in working memory in aged individuals seems to benefit from
      lateralized involvement of the superior parietal lobule.

PMID- 29593524
TI  - The Association of Aging and Aerobic Fitness With Memory.
AB  - The present study examined the differential effects of aging and fitness on
      memory. Ninety-five young adults (YA) and 81 older adults (OA) performed the
      Mnemonic Similarity Task (MST) to assess high-interference memory and general
      recognition memory. Age-related differences in high-interference memory were
      observed across the lifespan, with performance progressively worsening from young
      to old. In contrast, age-related differences in general recognition memory were
      not observed until after 60 years of age. Furthermore, OA with higher aerobic
      fitness had better high-interference memory, suggesting that exercise may be an
      important lifestyle factor influencing this aspect of memory. Overall, these
      findings suggest different trajectories of decline for high-interference and
      general recognition memory, with a selective role for physical activity in
      promoting high-interference memory.

PMID- 29593526
TI  - Tricaproin Isolated From Simarouba glauca Inhibits the Growth of Human Colorectal
      Carcinoma Cell Lines by Targeting Class-1 Histone Deacetylases.
AB  - While anticancer properties of Simarouba glauca (SG, commonly known as Paradise
      tree) are well documented in ancient literature, the underlying mechanisms
      leading to cancer cell death begin to emerge very recently. The leaves of SG have
      been used as potential source of anticancer agents in traditional medicine.
      Recently attempts have been made to isolate anticancer agents from the leaves of
      SG using solvent extraction, which identified quassinoids as the molecules with
      tumoricidal activity. However, it is not known whether the anti-cancer potential
      of SG leaves is just because of quassinoids alone or any other phytochemicals
      also contribute for the potency of SG leaf extracts. Therefore, SG leaves were
      first extracted with hexane, chloroform, ethyl acetate, 70% ethanol, water and
      anti-cancer potential (for inhibiting colorectal cancer (CRC) cells HCT-116 and
      HCT-15 proliferation) determined using Sulforhodamine-B (SRB) assay. The
      chloroform fraction with maximal anticancer activity was further fractionated by
      activity-guided isolation procedure and structure of the most potent compound
      determined using spectral analysis. Analysis of the structural characterization
      data showed the presence of tricaproin (TCN). TCN inhibited CRC cells growth in a
      time- and dose dependent manner but not the normal cell line BEAS-2B.
      Mechanistically, TCN reduced oncogenic Class-I Histone deacetylases (HDACs)
      activity, followed by inducing apoptosis in cells. In conclusion, the anti-cancer
      potential of SG is in part due to the presence of TCN in the leaves.

PMID- 29593528
TI  - A Statistical Thermodynamic Model for Ligands Interacting With Ion Channels:
      Theoretical Model and Experimental Validation of the KCNQ2 Channel.
AB  - Ion channels are important therapeutic targets, and their pharmacology is
      becoming increasingly important. However, knowledge of the mechanism of
      interaction of the activators and ion channels is still limited due to the
      complexity of the mechanisms. A statistical thermodynamic model has been
      developed in this study to characterize the cooperative binding of activators to
      ion channels. By fitting experimental concentration-response data, the model
      gives eight parameters for revealing the mechanism of an activator potentiating
      an ion channel, i.e., the binding affinity (KA ), the binding cooperative
      coefficients for two to four activator molecules interacting with one channel
      (gamma, MU, and nu), and the channel conductance coefficients for four activator
      binding configurations of the channel (a, b, c, and d). Values for the model
      parameters and the mechanism underlying the interaction of ztz240, a proven KCNQ2
      activator, with the wild-type channel have been obtained and revealed by fitting
      the concentration-response data of this activator potentiating the outward
      current amplitudes of KCNQ2. With these parameters, our model predicted an
      unexpected bi-sigmoid concentration-response curve of ztz240 activation of the WT
      F137A mutant heteromeric channel that was in good agreement with the experimental
      data determined in parallel in this study, lending credence to the assumptions on
      which the model is based and to the model itself. Our model can provide a better
      fit to the measured data than the Hill equation and estimates the binding
      affinity, as well as the cooperative coefficients for the binding of activators
      and conductance coefficients for binding states, which validates its use in
      studying ligand-channel interaction mechanisms.

PMID- 29593525
TI  - The Aging of Iron Man.
AB  - Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis.
      Iron dyshomeostasis has become a molecular signature associated with aging which
      is accompanied by progressive decline in cognitive processes. A common theme in
      neurodegenerative diseases where age is the major risk factor, iron
      dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation,
      neurodegeneration, and neurobehavioral deficits. There is a great need to
      determine the mechanisms governing perturbations in iron metabolism, in
      particular to distinguish between physiological and pathological aging to
      generate fruitful therapeutic targets for neurodegenerative diseases. The aim of
      the present review is to focus on the age-related alterations in brain iron
      metabolism from a cellular and molecular biology perspective, alongside genetics,
      and neuroimaging aspects in man and rodent models, with respect to normal aging
      and neurodegeneration. In particular, the relationship between iron
      dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of
      systemic iron overload on the brain. Based on the evidence discussed here, we
      suggest a synergistic use of iron-chelators and anti-inflammatories as putative
      anti-brain aging therapies to counteract pathological aging in neurodegenerative
      diseases.

PMID- 29593529
TI  - Pathway-Based Analysis of Genome-Wide Association Data Identified SNPs in HMMR as
      Biomarker for Chemotherapy- Induced Neutropenia in Breast Cancer Patients.
AB  - Neutropenia secondary to chemotherapy in breast cancer patients can be life
      threatening and there are no biomarkers available to predict the risk of drug
      induced neutropenia in those patients. We previously performed a genome-wide
      association study (GWAS) for neutropenia events in women with breast cancer who
      were treated with 5-fluorouracil, epirubicin and cyclophosphamide and recruited
      to the SUCCESS-A trial. A genome-wide significant single-nucleotide polymorphism
      (SNP) signal in the tumor necrosis factor superfamily member 13B (TNFSF13B) gene,
      encoding the cytokine B-cell activating factor (BAFF), was identified in that
      GWAS. Taking advantage of these existing GWAS data, in the present study we
      utilized a pathway-based analysis approach by leveraging knowledge of the
      pharmacokinetics and pharmacodynamics of drugs and breast cancer pathophysiology
      to identify additional SNPs/genes associated with the underlying etiology of
      chemotherapy-induced neutropenia. We identified three SNPs in the hyaluronan
      mediated motility receptor (HMMR) gene that were significantly associated with
      neutropenia (p < 1.0E-04). Those three SNPs were trans-expression quantitative
      trait loci for the expression of TNFSF13B (p < 1.0E-04). The minor allele of
      these HMMR SNPs was associated with a decreased TNFSF13B mRNA level. Additional
      functional studies performed with lymphoblastoid cell lines (LCLs) demonstrated
      that LCLs possessing the minor allele for the HMMR SNPs were more sensitive to
      drug treatment. Knock-down of TNFSF13B in LCLs and HL-60 promyelocytic cells and
      treatment of those cells with BAFF modulated the cell sensitivity to chemotherapy
      treatment. These results demonstrate that HMMR SNP-dependent cytotoxicity of
      these chemotherapeutic agents might be related to TNFSF13B expression level. In
      summary, utilizing a pathway-based approach for the analysis of GWAS data, we
      identified additional SNPs in the HMMR gene that were associated with neutropenia
      and also were correlated with TNFSF13B expression.

PMID- 29593527
TI  - Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics
      Approaches: Impact on Rational Drug Design.
AB  - The primary goal of rational drug discovery is the identification of selective
      ligands which act on single or multiple drug targets to achieve the desired
      clinical outcome through the exploration of total chemical space. To identify
      such desired compounds, computational approaches are necessary in predicting
      their drug-like properties. G Protein-Coupled Receptors (GPCRs) represent one of
      the largest and most important integral membrane protein families. These
      receptors serve as increasingly attractive drug targets due to their relevance in
      the treatment of various diseases, such as inflammatory disorders, metabolic
      imbalances, cardiac disorders, cancer, monogenic disorders, etc. In the last
      decade, multitudes of three-dimensional (3D) structures were solved for diverse
      GPCRs, thus referring to this period as the "golden age for GPCR structural
      biology." Moreover, accumulation of data about the chemical properties of GPCR
      ligands has garnered much interest toward the exploration of GPCR chemical space.
      Due to the steady increase in the structural, ligand, and functional data of
      GPCRs, several cheminformatics approaches have been implemented in its drug
      discovery pipeline. In this review, we mainly focus on the cheminformatics-based
      paradigms in GPCR drug discovery. We provide a comprehensive view on the ligand-
      and structure-based cheminformatics approaches which are best illustrated via
      GPCR case studies. Furthermore, an appropriate combination of ligand-based
      knowledge with structure-based ones, i.e., integrated approach, which is emerging
      as a promising strategy for cheminformatics-based GPCR drug design is also
      discussed.

PMID- 29593530
TI  - Mitochondrial Fission Is Required for Angiotensin II-Induced Cardiomyocyte
      Apoptosis Mediated by a Sirt1-p53 Signaling Pathway.
AB  - Hypertension-induced cardiac apoptosis is a major contributor to early-stage
      heart-failure. Our previous studies have found that p53-mediated mitochondrial
      fission is involved in aldosterone-induced podocyte apoptosis. However, it is not
      clear that whether p53-induced mitochondrial fission is critical for hypertensive
      Angiotensin II (AngII)-induced cardiomyocyte apoptosis. In this study, we found
      that inhibition of the mitochondrial fission protein Drp1 (dynamin-related
      protein 1) by Mdivi-1 prevented cardiomyocyte apoptosis and cardiac remodeling in
      SHRs. In vitro we found that treatment of cultured neonatal rat cardiomyocytes
      with AngII induced Drp1 expression, mitochondrial fission, and apoptosis.
      Knockdown of Drp1 inhibited AngII-induced mitochondrial fission and cardiomyocyte
      apoptosis. Furthermore, AngII induced p53 acetylation. Knockdown of p53 inhibited
      AngII-induced Drp1 expression, mitochondrial fission, and cardiomyocyte
      apoptosis. Besides, we found that Sirt1 was able to reverse AngII-induced p53
      acetylation and its binding to the Drp1 promoter, which subsequently inhibited
      mitochondrial fission and eventually attenuated cardiomyocyte apoptosis.
      Collectively, these results suggest that AngII degrades Sirt1 to increase p53
      acetylation, which induces Drp1 expression and eventually results in
      cardiomyocyte apoptosis. Sirt1/p53/Drp1dependent mitochondrial fission may be a
      valuable therapeutic target for hypertension induced heart failure.

PMID- 29593531
TI  - Stereoisomers of Saponins in Panax notoginseng (Sanqi): A Review.
AB  - Panax notoginseng (Sanqi), a traditional Chinese medical drug which has been
      applied to medical use for over four centuries, contains high content of
      dammarane-type tetracyclic triterpenoid saponins. A number of stereoisomeric
      dammarane-type saponins exist in this precious herb, and some are particularly
      regarded as "biomarkers" in processed notoginseng. Contemporary researches have
      indicated that some saponin stereoisomers may show stereospecific pharmacological
      activities, such as anti-tumor, antioxidative, anti-photoaging, anti
      inflammatory, antidiabetic, and neuro-protective activities, as well as
      stereoselective effects on ion channel current regulation, cardiovascular system,
      and immune system. The current review provides a comprehensive overview of
      chemical compositions of raw and processed P. notoginseng with a particular
      emphasis on saponin stereoisomers. Besides, the pharmacological and
      pharmacokinetic researches, as well as determination and biotechnological
      preparation methods of stereoisomeric saponins in notoginseng are discussed
      extensively.

PMID- 29593533
TI  - A New Search Method Using Association Rule Mining for Drug-Drug Interaction Based
      on Spontaneous Report System.
AB  - Background: Adverse events (AEs) can be caused not only by one drug but also by
      the interaction between two or more drugs. Therefore, clarifying whether an AE is
      due to a specific suspect drug or drug-drug interaction (DDI) is useful
      information for proper use of drugs. Whereas previous reports on the search for
      drug-induced AEs with signal detection using spontaneous reporting systems (SRSs)
      are numerous, reports on drug interactions are limited. This is because in
      methods that use "a safety signal indicator" (signal), which is frequently used
      in pharmacovigilance, a huge number of combinations must be prepared when signal
      detection is performed, and each risk index must be calculated, which makes
      interaction search appear unrealistic. Objective: In this paper, we propose
      association rule mining (AR) using large dataset analysis as an alternative to
      the conventional methods (additive interaction model (AI) and multiplicative
      interaction model (MI)). Methods: The data source used was the Japanese Adverse
      Drug Event Report database. The combination of drugs for which the risk index is
      detected by the "combination risk ratio (CR)" as the target was assumed to be
      true data, and the accuracy of signal detection using the AR methods was
      evaluated in terms of sensitivity, specificity, Youden's index, F-score. Results:
      Our experimental results targeting Stevens-Johnson syndrome indicate that AR has
      a sensitivity of 99.05%, specificity of 92.60%, Youden's index of 0.917, F-score
      of 0.876, AI has a sensitivity of 95.62%, specificity of 96.92%, Youden's index
      of 0.925, and F-score of 0.924, and MI has a sensitivity of 65.46%, specificity
      of 98.78%, Youden's index of 0.642, and F-score of 0.771. This result was about
      the same level as or higher than the conventional method. Conclusions: If you use
      similar calculation methods to create combinations from the database, not only
      for SJS, but for all AEs, the number of combinations would be so enormous that it
      would be difficult to perform the calculations. However, in the AR method, the
      "Apriori algorithm" is used to reduce the number of calculations. Thus, the
      proposed method has the same detection power as the conventional methods, with
      the significant advantage that its calculation process is simple.

PMID- 29593532
TI  - (-)-Epigallocatechin-3-Gallate Ameliorates Atherosclerosis and Modulates Hepatic
      Lipid Metabolic Gene Expression in Apolipoprotein E Knockout Mice: Involvement of
      TTC39B.
AB  - Background: Aberrant chronic inflammation and excess accumulation of lipids play
      a pivotal role in the occurrence and progression of atherosclerosis. (-)
      Epigallocatechin-3-gallate (EGCG), the major catechins in green tea, displayed
      anti-atherosclerotic properties in vivo and in vitro. However, the effects and
      underlying mechanism of EGCG on atherosclerosis remain unclear. Methods: Male
      apolipoprotein E-knockout (ApoE-/-) mice (7 weeks old) fed with high-fat diet
      (HFD) were treated with normal saline or EGCG (40 mg/kg/d, i.g.) for 18 weeks.
      Atherosclerotic plaque and liver lipid accumulation were measured by Oil Red
      staining. Plasma lipids and cytokines were detected using commercial kits. The
      expression of protein and mRNA was analyzed by western blot and quantitative real
      time reverse transcription-polymerase chain reaction, respectively. Results: EGCG
      administration markedly attenuated atherosclerotic plaque formation in HFD-fed
      ApoE-/- mice, which were accompanied by increased plasma interleukin-10 (IL-10)
      level and decreased plasma IL-6 and tumor necrosis factor-alpha (TNF-alpha)
      levels. In addition, EGCG modulated high-fat-induced dyslipidemia, evidencing by
      decreased total cholesterol (TC) and low-density lipoprotein levels and increased
      high-density lipoprotein level. Meanwhile, EGCG treatment alleviated high-fat
      mediated liver lipid accumulation and decreased liver TC and triglyceride.
      Mechanistically, EGCG significantly modulated high-fat-induced hepatic
      tetratricopeptide repeat domain protein 39B (TTC39B) expression and its related
      genes (Lxrbeta, Abcg5, Abcg8, Abca1, Srebf1, Scd1, Scd2, Fas, Elovl5, Mylip)
      expression in liver from ApoE-/- mice. Notably, EGCG remarkably induced hepatic
      liver X receptor alpha (LXRalpha) and LXRbeta expression and inhibited both
      precursor and mature sterol regulatory element binding transcription factor-1
      (SREBP-1) expression. Conclusion: Taken together, our data for the first time
      suggested that TTC39B was involved in EGCG-mediated anti-atherosclerotic effects
      through modulation of LXR/SREBP-1 pathway.

PMID- 29593534
TI  - East Indian Sandalwood Oil Is a Phosphodiesterase Inhibitor: A New Therapeutic
      Option in the Treatment of Inflammatory Skin Disease.
AB  - Cyclic adenosine monophosphate phosphodiesterases (PDEs) regulate pro
      inflammatory cytokine production. One isoform, PDE4, is overactive in chronic
      relapsing inflammatory skin diseases: psoriasis and eczema/atopic dermatitis, and
      in several cancers. East Indian sandalwood oil (EISO) has significant anti
      inflammatory properties. Here, we report that 75% of pediatric eczema/atopic
      dermatitis patients treated with topical EISO formulations achieved a >50%
      reduction in their Eczema Area and Severity Index score. EISO treatment of a
      psoriasis model reduced PDE4 expression and reversed histopathology. EISO
      directly inhibited PDE enzymatic activity in vitro. In lipopolysaccharide
      stimulated human dermal fibroblast, BEAS-2B, A549, and THP-1 cells, EISO
      suppressed total cellular PDE activity, PDE4, and 7 transcript levels, nuclear
      factor kappa B (NF-kappaB) activation, and pro-inflammatory cytokines/chemokine
      production. These results suggest that EISO anti-inflammatory activity is
      mediated through suppressing PDE activity, thus facilitating cAMP-regulated
      inhibition of NF-kappaB and indicate EISO as an attractive natural therapeutic
      for chronic and acute inflammatory disorders.

PMID- 29593535
TI  - Vortioxetine Improves Context Discrimination in Mice Through a Neurogenesis
      Independent Mechanism.
AB  - Major Depressive Disorders (MDD) patients may exhibit cognitive deficits and it
      is currently unclear to which degree treatment with antidepressants may affect
      cognitive function. Preclinical and clinical observations showed that
      vortioxetine (VORT, an antidepressant with multimodal activity), presents
      beneficial effects on aspects of cognitive function. In addition, VORT treatment
      increases adult hippocampal neurogenesis (AHN) in rodents, a candidate mechanism
      for antidepressant activity. Pattern separation (PS) is the ability to
      discriminate between two similar contexts/events generating two distinct and non
      overlapping representations. Impaired PS may lead to overgeneralization and
      anxiety disorders. If PS impairments were described in depressed patients, the
      consequences of antidepressant treatment on context discrimination (CD) are still
      in its infancy. We hypothesized that VORT-increased AHN may improve CD. Thus, in
      an attempt to elucidate the molecular mechanism underpinning VORT treatment
      effects on CD, a rodent model of PS, the role of AHN and stress-induced c-Fos
      activation was evaluated in the adult mouse hippocampus. Chronic treatment with
      VORT (1.8 g/kg of food weight; corresponding to a daily dose of 10 mg/kg, 3
      weeks) improved CD in mice. Interestingly, chronic treatment with VORT reversed
      ablation of AHN-induced delay in CD and freezing behavior. VORT treatment
      decreased stress-induced c-Fos activation in the dorsal but not ventral dentate
      gyrus. VORT treatment did not affect c-Fos activity in the hippocampus of mice
      with ablated neurogenesis. This study highlights a role of VORT in CD, which may
      be independent from AHN and hippocampal c-Fos activation. Further studies
      elucidating the mechanisms underlying VORT's effects in CD could contribute to
      future strategies for alleviating the disease burden for individuals suffering
      from depression and/or anxiety disorders.

PMID- 29593536
TI  - A Novel Dual HDAC6 and Tubulin Inhibitor, MPT0B451, Displays Anti-tumor Ability
      in Human Cancer Cells in Vitro and in Vivo.
AB  - The combination cancer therapy is a new strategy to circumvent drug resistance
      for the treatment of high metastasis and advanced malignancies. Herein, we
      developed a synthesized compound MPT0B451 that display inhibitory effect against
      histone deacetylase (HDAC) 6 and tubulin assembly. Our data demonstrated that
      MPT0B451 significantly inhibited cancer cell growths in HL-60 and PC-3 cells due
      to inhibition of HDAC activity. MPT0B451 also markedly increased caspase-mediated
      apoptosis in these cells. The cell cycle analysis showed mitotic arrest induced
      by MPT0B451 with enhanced expression of G2/M transition proteins. Moreover,
      molecular docking analysis supported MPT0B451 as a dual HDAC6 and tubulin
      inhibitor. Finally, MPT0B451 led to tumor growth inhibition (TGI) in HL-60 and PC
      3 xenograft models. These findings indicated that MPT0B451 has dual inhibition
      effects for HDAC6 and tubulin, and also contributed to G2/M arrest followed by
      apoptotic induction. Together, our results suggested that MPT0B451 may serve as a
      potent anti-cancer treatment regimen in human prostate cancer and acute myeloid
      leukemia.

PMID- 29593537
TI  - Acute Pharmacological Effects of 2C-B in Humans: An Observational Study.
AB  - 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenylethylamine
      derivative, structurally similar to mescaline. It is a serotonin 5
      hydroxytryptamine-2A (5-HT2A), 5-hydroxytryptamine-2B (5-HT2B), and 5
      hydroxytryptamine-2C (5-HT2C) receptor partial agonist used recreationally as a
      new psychoactive substance. It has been reported that 2C-B induces mild
      psychedelic effects, although its acute pharmacological effects and
      pharmacokinetics have not yet been fully studied in humans. An observational
      study was conducted to assess the acute subjective and physiological effects, as
      well as pharmacokinetics of 2C-B. Sixteen healthy, experienced drug users self
      administered an oral dose of 2C-B (10, 15, or 20 mg). Vital signs (blood pressure
      and heart rate) were measured at baseline 1, 2, 3, 4, and 6 hours (h). Each
      participant completed subjective effects using three rating scales: the visual
      analog scale (VAS), the Addiction Research Centre Inventory (ARCI), and the
      Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA
      SSE) at baseline, 2-3 and 6 h after self-administration (maximum effects along 6
      h), and the Hallucinogenic Rating Scale (maximum effects along 6 h). Oral fluid
      (saliva) was collected to assess 2C-B and cortisol concentrations during 24 h.
      Acute administration of 2C-B increased blood pressure and heart rate. Scores of
      scales related to euphoria increased (high, liking, and stimulated), and changes
      in perceptions (distances, colors, shapes, and lights) and different body
      feelings/surrounding were produced. Mild hallucinating effects were described in
      five subjects. Maximum concentrations of 2C-B and cortisol were reached at 1 and
      3 h after self-administration, respectively. Oral 2C-B at recreational doses
      induces a constellation of psychedelic/psychostimulant-like effects similar to
      those associated with serotonin-acting drugs.

PMID- 29593538
TI  - Salidroside Inhibits Myogenesis by Modulating p-Smad3-Induced Myf5 Transcription.
AB  - Aim: Salidroside is an active compound extracted from Rhodiola rosea which is
      used to alleviate fatigue and enhance endurance in high altitude regions. Some
      studies have demonstrated that salidroside can affect precursor cell
      differentiation in hematopoietic stem cells, erythrocytes, and osteoblasts. The
      aim of this study was to investigate the effect of salidroside on myoblast
      differentiation and to explore the underlying molecular mechanisms of this
      effect. Methods: C2C12 myoblast cells were treated with different concentrations
      of salidroside in differentiation media. Real-time PCR, Western blotting, and
      immunofluorescence assay were employed to evaluate the effects of salidroside on
      C2C12 differentiation. RNA interference was used to reveal the important role of
      Myf5 in myogenesis inhibited by salidroside. Chromatin Immunoprecipitation and
      dual-luciferase reporter assay were utilized to explore the underlying mechanisms
      of salidroside-induced upregulation of Myf5. Results: We found that salidroside
      inhibits myogenesis by downregulating MyoD and myogenin, preserves
      undifferentiated reserve cell pools by upregulating Myf5. Knocking down Myf5
      expression significantly rescued the myogenesis inhibited by salidroside. The
      effect of salidroside on myogenesis was associated with increased phosphorylated
      Smad3 (p-Smad3). Both SIS3 (Specific inhibitor of p-Smad3) and dominant negative
      Smad3 plasmid (DN-Smad3) attenuated the inhibitory effect of salidroside on C2C12
      differentiation. Moreover, the induction of Myf5 transcription by salidroside was
      dependent on a Smad-binding site in the promoter region of Myf5 gene. Conclusion
      and Implications: Our findings identify a novel role and mechanism for
      salidroside in regulating myogenesis through p-Smad3-induced Myf5 transcription,
      which may have implications for its further application in combating degenerative
      muscular diseases caused by depletion of muscle stem cells, such as Duchenne
      muscular dystrophy or sarcopenia.

PMID- 29593539
TI  - Optimization of Cholinesterase-Based Catalytic Bioscavengers Against
      Organophosphorus Agents.
AB  - Organophosphorus agents (OPs) are irreversible inhibitors of acetylcholinesterase
      (AChE). OP poisoning causes major cholinergic syndrome. Current medical counter
      measures mitigate the acute effects but have limited action against OP-induced
      brain damage. Bioscavengers are appealing alternative therapeutic approach
      because they neutralize OPs in bloodstream before they reach physiological
      targets. First generation bioscavengers are stoichiometric bioscavengers.
      However, stoichiometric neutralization requires administration of huge doses of
      enzyme. Second generation bioscavengers are catalytic bioscavengers capable of
      detoxifying OPs with a turnover. High bimolecular rate constants (kcat/Km > 106 M
      1min-1) are required, so that low enzyme doses can be administered.
      Cholinesterases (ChE) are attractive candidates because OPs are hemi-substrates.
      Moderate OP hydrolase (OPase) activity has been observed for certain natural ChEs
      and for G117H-based human BChE mutants made by site-directed mutagenesis.
      However, before mutated ChEs can become operational catalytic bioscavengers their
      dephosphylation rate constant must be increased by several orders of magnitude.
      New strategies for converting ChEs into fast OPase are based either on
      combinational approaches or on computer redesign of enzyme. The keystone for
      rational conversion of ChEs into OPases is to understand the reaction mechanisms
      with OPs. In the present work we propose that efficient OP hydrolysis can be
      achieved by re-designing the configuration of enzyme active center residues and
      by creating specific routes for attack of water molecules and proton transfer.
      Four directions for nucleophilic attack of water on phosphorus atom were defined.
      Changes must lead to a novel enzyme, wherein OP hydrolysis wins over competing
      aging reactions. Kinetic, crystallographic, and computational data have been
      accumulated that describe mechanisms of reactions involving ChEs. From these
      studies, it appears that introducing new groups that create a stable H-bonded
      network susceptible to activate and orient water molecule, stabilize transition
      states (TS), and intermediates may determine whether dephosphylation is favored
      over aging. Mutations on key residues (L286, F329, F398) were considered. QM/MM
      calculations suggest that mutation L286H combined to other mutations favors water
      attack from apical position. However, the aging reaction is competing. Axial
      direction of water attack is not favorable to aging. QM/MM calculation shows that
      F329H+F398H-based multiple mutants display favorable energy barrier for fast
      reactivation without aging.

PMID- 29593540
TI  - Purinergic Ligands as Potential Therapeutic Tools for the Treatment of
      Inflammation-Related Intestinal Diseases.
AB  - Inflammation-related intestinal diseases are a set of various conditions
      presenting an overactive enteric immune system. A continuous overproduction of
      pro-inflammatory cytokines and a decreased production of anti-inflammatory
      modulators are generally observed, while morpho-functional alterations of the
      enteric nervous system lead to intestinal secretory and motor dysfunctions. The
      factors at the basis of these conditions are still to be totally identified and
      current therapeutic strategies are aimed only at achieving and maintaining
      remission states, by using therapeutic tools like aminosalicylates,
      corticosteroids, immunomodulators, biological drugs (i.e., monoclonal
      antibodies), and eventually surgery. Recent reports described a key role of
      purinergic mediators (i.e., adenosine and its nucleotides ATP and ADP) in the
      regulation of the activity of immune cells and enteric nervous system, showing
      also that alterations of the purinergic signaling are linked to pathological
      conditions of the intestinal tract. These data prompted to a series of
      investigations to test the therapeutic potential for inflammation-related
      intestinal conditions of compounds able to restore or modulate an altered
      purinergic signaling within the gut. This review provides an overview on these
      investigations, describing the results of preclinical and/or clinical evaluation
      of compounds able to stimulate or inhibit specific P2 (i.e., P2X7) or P1 (i.e.,
      A2A or A3) receptor signaling and to modify the adenosine levels through the
      modulation of enzymes activity (i.e., Adenosine Deaminase) or nucleoside
      transporters. Recent developments in the field are also reported and the most
      promising purine-based therapeutic strategies for the treatment of inflammation
      related gastrointestinal disorders are schematically summarized.

PMID- 29593541
TI  - A Preliminary Investigation on Smokeless Tobacco Use and Its Cognitive Effects
      Among Athletes.
AB  - Introduction: Among athletes, an increasing use of nicotine via smokeless tobacco
      has been reported. However, there are currently unanswered questions about
      whether the use by athletes is due to nicotine's addictive properties and/or to
      benefits in physical and cognitive performance (e.g., decision-making). In this
      original article we reported about, (i) snus-induced reinforcing effects among
      snus-user athletes (Survey) and (ii) the effects of snus on the Iowa Gambling
      Task (IGT) in snus-user skiers (Experimental study). IGT is an experimental
      neuropsychological task that has been previously used on athletes and addicts to
      test decision-making. Methods: Survey: data were collected with the modified
      Cigarette Evaluation Questionnaire (mCEQ) that was administered to 61 winter
      sport athlete snus-users in Northern Italy. Experimental study: IGT data
      included: amount of money earned, number of choices from advantageous and
      disadvantageous decks and overall net score. Eighteen male snus-users were tested
      under satiety or after 12-h abstinence conditions according to a crossover
      design. Results: Survey: the comparison between occasional vs. regular snus-users
      showed a statistically significant difference in satisfaction (P = 0.0088), calm
      (P = 0.0252), and enjoyment (P = 0.0001) mCEQ items suggesting a snus
      intake/effect relationship. Experimental study: significantly higher IGT net
      scores were found during the first 20 choice cards after abstinence vs. satiety
      conditions (P = 0.0024). Conclusion: In the Survey, regular snus use induces
      greater satisfaction and psychological reward than occasional use. In the
      Experimental study, snus intake might produce an early and transient cognitive
      improvement on IGT in abstinent snus-users, presumably acting as a withdrawal
      relief.

PMID- 29593542
TI  - Apigenin and Luteolin Attenuate the Breaching of MDA-MB231 Breast Cancer
      Spheroids Through the Lymph Endothelial Barrier in Vitro.
AB  - Flavonoids, present in fruits, vegetables and traditional medicinal plants, show
      anticancer effects in experimental systems and are reportedly non-toxic. This is
      a favorable property for long term strategies for the attenuation of lymph node
      metastasis, which may effectively improve the prognostic states in breast cancer.
      Hence, we studied two flavonoids, apigenin and luteolin exhibiting strong bio
      activity in various test systems in cancer research and are readily available on
      the market. This study has further advanced the mechanistic understanding of
      breast cancer intravasation through the lymphatic barrier. Apigenin and luteolin
      were tested in a three-dimensional (3-D) assay consisting of MDA-MB231 breast
      cancer spheroids and immortalized lymph endothelial cell (LEC) monolayers. The 3
      D model faithfully resembles the intravasation of breast cancer emboli through
      the lymphatic vasculature. Western blot analysis, intracellular Ca2+
      determination, EROD assay and siRNA transfection revealed insights into
      mechanisms of intravasation as well as the anti-intravasative outcome of
      flavonoid action. Both flavonoids suppressed pro-intravasative trigger factors in
      MDA-MB231 breast cancer cells, specifically MMP1 expression and CYP1A1 activity.
      A pro-intravasative contribution of FAK expression in LECs was established as FAK
      supported the retraction of the LEC monolayer upon contact with cancer cells
      thereby enabling them to cross the endothelial barrier. As mechanistic basis,
      MMP1 caused the phosphorylation (activation) of FAK at Tyr397 in LECs. Apigenin
      and luteolin prevented MMP1-induced FAK activation, but not constitutive FAK
      phosphorylation. Luteolin, unlike apigenin, inhibited MMP1-induced Ca2+ release.
      Free intracellular Ca2+ is a central signal amplifier triggering LEC retraction
      through activation of the mobility protein MLC2, thereby enhancing intravasation.
      FAK activity and Ca2+ levels did not correlate. This implicates that the pro
      intravasative contribution of FAK and of Ca2+ release in LECs was independent of
      each other and explains the better anti-intravasative effects of luteolin in
      vitro. In specific formulations, flavonoid concentrations causing significant
      anti-intravasative effects, can certainly be achieved in vivo. As the therapeutic
      strategy has to be based on permanent flavonoid treatment both the beneficial and
      adverse effects have to be investigated in future studies.

PMID- 29593543
TI  - The Trace Amine-Associated Receptor 1 Agonist 3-Iodothyronamine Induces Biased
      Signaling at the Serotonin 1b Receptor.
AB  - Trace amine-associated receptors (TAARs) belong to the class A G-protein-coupled
      receptors (GPCR) and are evolutionary related to aminergic receptors. TAARs have
      been identified to mediate effects of trace amines. TAAR1 signaling is mainly
      mediated via activation of the Gs/adenylyl cyclase pathway. In addition to
      classical trace amines, TAAR1 can also be activated by the thyroid hormone
      derivative 3-iodothyronamine (3-T1AM). Pharmacological doses of 3-T1AM induced
      metabolic and anapyrexic effects, which might be centrally mediated in the
      hypothalamus in rodents. However, the observed anapyrexic effect of 3-T1AM
      persists in Taar1 knock-out mice which raises the question whether further GPCRs
      are potential targets for 3-T1AM and mediate the observed physiological effect.
      Anapyrexia has been observed to be related to action on aminergic receptors such
      as the serotonin receptor 1b (5-HT1b). This receptor primarily activates the Gi/o
      mediated pathway and PLC signaling through the Gbetagamma of Gi/o. Since the
      expression profiles of TAAR1 and 5-HT1b overlap, we questioned whether 3-T1AM may
      activate 5-HT1b. Finally, we also evaluated heteromerization between these two
      GPCRs and tested signaling under co-expressed conditions. In this study, we
      showed, that 3-T1AM can induce Gi/o signaling through 5-HT1b in a concentration
      of 10 MUM. Strikingly, at 5-HT1b the ligand 3-T1AM only activates the Gi/o
      mediated reduction of cAMP accumulation, but not PLC activation. Co-stimulation
      of 5-HT1b by both ligands did not lead to additive or synergistic signaling
      effects. In addition, we confirmed the capacity for heteromerization between
      TAAR1 and 5-HT1b. Under co-expression of TAAR1 and HTR1b, 3-T1AM action is only
      mediated via TAAR1 and activation of 5-HT1b is abrogated. In conclusion, we found
      evidence for 5-HT1b as a new receptor target for 3-T1AM, albeit with a different
      signaling effect than the endogenous ligand. Altogether, this indicates a complex
      interrelation of signaling effects between the investigated GPCRs and respective
      ligands.

PMID- 29593544
TI  - The Influence of Shuttle-Shape Emodin Nanoparticles on the Streptococcus suis
      Biofilm.
AB  - Biofilm is one of the most important physiological protective barriers of the
      Streptococcus suis (S. suis), and it is also one of the primary causes of
      hindrance to drug infiltration, reduction of bactericidal effects, and the
      development of antibiotic resistance. In order to intervene or eliminate S. suis
      biofilm, shuttle-shape emodin-loaded nanoparticles were developed in our study.
      The emodin nanoparticles were prepared by emodin and gelatin-cyclodextrin which
      was synthesized as drug carrier, and the nanoparticles were 174 nm in size, -4.64
      mv in zeta potential, and exhibited a sustained emodin release. Moreover, the
      delivery kinetics of nanoparticles were also explored in our study. The confocal
      laser scanning microscopy and colony forming unit enumeration experiment
      indicated that nanoparticles could increase drug infiltration and uptake by
      biofilm. The flow cytometry system analysis showed that nanoparticles could be up
      taken by 99% of the bacteria cells. TCP assay and scanning electron microscopy
      showed that the nanoparticles had better effect on biofilm inhibition and
      elimination when compared with emodin solution. These results revealed that the
      emodin nanoparticles had a better therapeutic effect on the S. suis biofilm in
      vitro.

PMID- 29593545
TI  - The Cytochrome P450-Mediated Metabolism Alternation of Four Effective Lignans
      From Schisandra chinensis in Carbon Tetrachloride-Intoxicated Rats and Patients
      With Advanced Hepatocellular Carcinoma.
AB  - It is highly valuable to study the pharmacokinetics of herbal components under
      the pathological condition of liver dysfunction for safe and rational use of
      herbal medicines. In this study, the pharmacokinetic profiles of four effective
      lignans from Schisandra chinensis (SC), schisandrin, schisantherin A,
      deoxyshisandrin and gamma-schisandrin, were investigated in carbon tetrachloride
      (CCl4)-intoxicated rats. The metabolism of the four lignans was also studied
      using microsomes from patients with advanced hepatocellular carcinoma. In situ
      intestinal and hepatic perfusions were conducted to clarify the contributions
      from impairments of gut and liver on the pharmacokinetics of the four schisandra
      lignans in CCl4-intoxicated rats. The metabolism in rat and human liver
      microsomes and transport in Caco-2 monolayer cell model were studied to reveal
      the key factors for the in vivo disposition of the four lignans. When SC
      alcoholic extract was orally administrated to CCl4-intoxicated rat for a short
      term (4 days), the pharmacokinetics of four active SC lignans was significantly
      changed while its hepatotherapeutic effect was not obviously observed. The plasma
      concentrations of the four schisandra lignans were dramatically elevated compared
      with the control. The Cmax, AUC and MRT were all increased or prolonged
      significantly while parameter CLz/F was obviously reduced in rat pretreated with
      CCl4. In hepatic perfusion study and liver microsomes incubation, it was found
      that the hepatic metabolism of the four lignans was markedly decreased mainly due
      to the activity reduction of multiple CYP450 isoenzymes involved the metabolism,
      which, eventually, might lead to the alternation of their pharmacokinetic
      profiles in CCl4-intoxicated rats or patients with advanced hepatocellular
      carcinoma. The pharmacokinetic studies of SC components in pathological situation
      of liver dysfunction are expected to provide useful data for rational and safe
      application of SC preparations in clinic or further pharmacological and
      toxicological research.

PMID- 29593546
TI  - Commentary: Neuronal regulation of type 2 innate lymphoid cells via neuromedin U.

PMID- 29593547
TI  - The Anticancer Activity of Sea Buckthorn [Elaeagnus rhamnoides (L.) A. Nelson].
AB  - Various parts of sea buckthorn [Elaeagnus rhamnoides (L.) A. Nelson],
      particularly the berries, known also as seaberries, or Siberian pineapples, are
      characterized by a unique composition of bioactive compounds: phenolic compounds,
      vitamins (especially vitamin C), unsaturated fatty acids, and phytosterols such
      as beta-sitosterol. These berries, together with the juices, jams, and oils made
      from them, have a range of beneficial antioxidant, anti-inflammatory, and
      anticancer effects. This short review discusses whether sea buckthorn may
      represent a "golden mean" for the treatment of cancers: It has anti-proliferation
      properties and can induce apoptosis and stimulate the immune system, and sea
      buckthorn oil counteracts many side effects of chemotherapy by restoring kidney
      and liver function, increasing appetite, and keeping patients in general good
      health. Although the anticancer activity of sea buckthorn has been confirmed by
      many in vitro and animal in vivo studies, the treatment and prophylactic doses
      for humans are unknown. Therefore, greater attention should be paid to the
      development of well-controlled and high-quality clinical experiments in this
      area.

PMID- 29593548
TI  - Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral
      Circulatory Impairments During Aging and Alzheimer's Disease.
AB  - Advanced aging, vascular dysfunction, and nitric oxide (NO) bioavailability are
      recognized risk factors for Alzheimer's disease (AD). However, the contribution
      of AD, per se, to this putative pathophysiological mechanism is still unclear. To
      better answer this point, we quantified cortical perfusion with arterial spin
      labeling (PVC-CBF), measured ultrasound internal carotid (ICA), and femoral (FA)
      artery blood flow in a group of patients with similar age (~78 years) but
      different cognitive impairment (i.e., mild cognitive impairment MCI, mild AD-AD1,
      moderate AD-AD2, and severe AD-AD3) and compared them to young and healthy old
      (aged-matched) controls. NO-metabolites and passive leg-movement (PLM) induced
      hyperemia were used to assess systemic vascular function. Ninety-eight
      individuals were recruited for this study. PVC-CBF, ICA, and FA blood flow were
      markedly (range of 9-17%) and significantly (all p < 0.05) reduced across the
      spectrum from YG to OLD, MCI, AD1, AD2, AD3 subjects. Similarly, plasma level of
      nitrates and the values of PLM were significantly reduced (range of 8-26%; p <
      0.05) among the six groups. Significant correlations were retrieved between
      plasma nitrates, PLM and PVC-CBF, CA, and FA blood flow. This integrative and
      comprehensive approach to vascular changes in aging and AD showed progressive
      changes in NO bioavailability and cortical, extracranial, and peripheral
      circulation in patients with AD and suggested that they are directly associated
      with AD and not to aging. Moreover, these results suggest that AD-related
      impairments of circulation are progressive and not confined to the brain. The
      link between cardiovascular and the central nervous systems degenerative
      processes in patients at different severity of AD is likely related to the
      depletion of NO.

PMID- 29593549
TI  - Functional Polarity of Microvascular Brain Endothelial Cells Supported by
      Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis.
AB  - The homeostatic regulation of large neutral amino acid (LNAA) concentration in
      the brain interstitial fluid (ISF) is essential for proper brain function. LNAA
      passage into the brain is primarily mediated by the complex and dynamic
      interactions between various solute carrier (SLC) transporters expressed in the
      neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major
      contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated
      trans-endothelial transport of LNAAs, however, could not be characterized
      precisely by available in vitro and in vivo standard methods so far. To
      circumvent these limitations, we have incorporated published in vivo data of rat
      brain into a robust computational model of NVU-LNAA homeostasis, allowing us to
      evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs
      across the blood brain barrier (BBB). We show that accounting for functional
      polarity of MBECs with either asymmetric LAT1 distribution between membranes
      and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is
      required to reproduce the experimentally measured brain ISF response to
      intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of
      these findings, we have also investigated the effect of IP administrated L
      tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and
      neurons. Finally, the computational model was shown to explain the trans
      stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a
      competitive LAT1 inhibitor.

PMID- 29593550
TI  - Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in
      Drosophila melanogaster.
AB  - Alcohol use disorder (AUD) is a major health, social and economic problem for
      which there are few effective treatments. The opiate antagonist naltrexone is
      currently prescribed clinically with mixed success. We have used naltrexone in an
      established behavioral assay (CAFE) in Drosophila melanogaster that measures the
      flies' preference for ethanol-containing food. We have confirmed that Drosophila
      exposed to ethanol develop a preference toward this drug and we demonstrate that
      naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol
      preference. This effect is not permanent, as preference for alcohol returns after
      discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced
      increase in protein kinase C activity. These findings are of interest because
      they confirm that Drosophila is a useful model for studying human responses to
      addictive drugs. Additionally because of the lack of a closely conserved opiate
      system in insects, our results could either indicate that a functionally related
      system does exist in insects or that in insects, and potentially also in mammals,
      naltrexone binds to alternative sites. Identifying such sites could lead to
      improved treatment strategies for AUD.

PMID- 29593551
TI  - Retinal Vessel Diameters and Physical Activity in Patients With Mild to Moderate
      Rheumatic Disease Without Cardiovascular Comorbidities.
AB  - Objectives: Low-grade systemic inflammation is responsible for atherosclerotic
      lesions in patients with rheumatic diseases. Vascular dysfunction is a precursor
      of atherosclerosis and can be improved by physical activity (PA). Our aim was to
      asses micro- and macrovascular function as well as PA and cardiorespiratory
      fitness (CRF) in patients with rheumatic diseases in the absence of
      cardiovascular (CV) comorbidities compared to controls. Methods: Fifty-one
      patients without CV comorbidities were compared to 35 controls. Retinal
      microvascular diameters were assessed using a Retinal Vessel Analyzer. Arterial
      stiffness (AST) was measured by applanation tonometry. CRF was assessed as peak
      oxygen consumption and PA was assessed with a questionnaire. Results: Retinal
      venular diameters were significantly wider in patients [median 221 MUm
      (interquartile range (IQR) 211, 231)] compared to controls [median 215 MUm (IQR
      196, 223); p = 0.01]. One hour increase of PA per week led to a venular
      constriction of -0.56 MUm (95%CI -1.09, -0.03; p = 0.04). In our patients with
      low disease activity (median DAS28 1.9; median BASDAI 2.8), no differences in AST
      were evident compared to controls. The association of PA and CRF with AST was not
      independent of blood pressure. Conclusions: Patients with rheumatic disease and
      mild-to-moderate disease activity show an impairment of the retinal
      microvasculature but not of large artery stiffness. Retinal vessel analysis seems
      to be a sensitive biomarker to unmask vascular impairments even in the absence of
      classic CV risk factors. PA may have the potential to counteract the development
      of small artery disease at early stages of rheumatic disease.

PMID- 29593552
TI  - KV4.3 Expression Modulates NaV1.5 Sodium Current.
AB  - In cardiomyocytes, the voltage-gated transient outward potassium current (Ito) is
      responsible for the phase-1 repolarization of the action potential (AP). Gain-of
      function mutations in KCND3, the gene encoding the Ito carrying KV4.3 channel,
      have been associated with Brugada syndrome (BrS). While the role of Ito in the
      pro-arrhythmic mechanism of BrS has been debated, recent studies have suggested
      that an increased Ito may directly affect cardiac conduction. However, the
      effects of an increased Ito on AP upstroke velocity or sodium current at the
      cellular level remain unknown. We here investigated the consequences of KV4.3
      overexpression on NaV1.5 current and consequent sodium channel availability. We
      found that overexpression of KV4.3 protein in HEK293 cells stably expressing
      NaV1.5 (HEK293-NaV1.5 cells) significantly reduced NaV1.5 current density without
      affecting its kinetic properties. In addition, KV4.3 overexpression decreased AP
      upstroke velocity in HEK293-NaV1.5 cells, as measured with the alternating
      voltage/current clamp technique. These effects of KV4.3 could not be explained by
      alterations in total NaV1.5 protein expression. Using computer simulations
      employing a multicellular in silico model, we furthermore demonstrate that the
      experimentally observed increase in KV4.3 current and concurrent decrease in
      NaV1.5 current may result in a loss of conduction, underlining the potential
      functional relevance of our findings. This study gives the first proof of concept
      that KV4.3 directly impacts on NaV1.5 current. Future studies employing
      appropriate disease models should explore the potential electrophysiological
      implications in (patho)physiological conditions, including BrS associated with
      KCND3 gain-of-function mutations.

PMID- 29593553
TI  - High-Resolution X-Ray Tomography: A 3D Exploration Into the Skeletal Architecture
      in Mouse Models Submitted to Microgravity Constraints.
AB  - Bone remodeling process consists in a slow building phase and in faster
      resorption with the objective to maintain a functional skeleton locomotion to
      counteract the Earth gravity. Thus, during spaceflights, the skeleton does not
      act against gravity, with a rapid decrease of bone mass and density, favoring
      bone fracture. Several studies approached the problem by imaging the bone
      architecture and density of cosmonauts returned by the different spaceflights.
      However, the weaknesses of the previously reported studies was two-fold: on the
      one hand the research suffered the small statistical sample size of almost all
      human spaceflight studies, on the other the results were not fully reliable,
      mainly due to the fact that the observed bone structures were small compared with
      the spatial resolution of the available imaging devices. The recent advances in
      high-resolution X-ray tomography have stimulated the study of weight-bearing
      skeletal sites by novel approaches, mainly based on the use of the mouse and its
      various strains as an animal model, and sometimes taking advantage of the
      synchrotron radiation support to approach studies of 3D bone architecture and
      mineralization degree mapping at different hierarchical levels. Here we report
      the first, to our knowledge, systematic review of the recent advances in studying
      the skeletal bone architecture by high-resolution X-ray tomography after
      submission of mice models to microgravity constrains.

PMID- 29593554
TI  - Effects of Resistance Training on Matrix Metalloproteinase Activity in Skeletal
      Muscles and Blood Circulation During Aging.
AB  - Aging is a complex, multifactorial process characterized by the accumulation of
      deleterious effects, including biochemical adaptations of the extracellular
      matrix (ECM). The purpose of this study was to investigate the effects of 12
      weeks of resistance training (RT) on metalloproteinase 2 (MMP-2) activity in
      skeletal muscles and, MMP-2 and MMP-9 activity in the blood circulation of young
      and old rats. Twenty-eight Wistar rats were randomly divided into four groups (n
      = 7 per group): young sedentary (YS); young trained (YT), old sedentary (OS), and
      old trained (OT). The stair climbing RT consisted of one training session every 2
      other day, with 8-12 dynamic movements per climb. The animals were euthanized 48
      h after the end of the experimental period. MMP-2 and MMP-9 activity was measured
      by zymography. There was higher active MMP-2 activity in the lateral
      gastrocnemius and flexor digitorum profundus muscles in the OT group when
      compared to the OS, YS, and YT groups (p <= 0.001). Moreover, there was higher
      active MMP-2 activity in the medial gastrocnemius muscle in the OT group when
      compared to the YS and YT groups (p <= 0.001). The YS group presented lower
      active MMP-2 activity in the soleus muscle than the YT, OS, OT groups (p <=
      0.001). With respect to active MMP-2/9 activity in the bloodstream, the OT group
      displayed significantly reduced activity (p <= 0.001) when compared to YS and YT
      groups. In conclusion, RT up-regulates MMP-2 activity in aging muscles, while
      down-regulating MMP-2 and MMP-9 in the blood circulation, suggesting that it may
      be a useful tool for the maintenance of ECM remodeling.

PMID- 29593555
TI  - Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in
      Diabetic GK Rats: Possible Involvement of FGF21.
AB  - Objective: Ileal transposition (IT) surgery has been reported to improve glucose
      and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful
      metabolic regulator. In the present study, we aimed to investigate the effects of
      IT surgery on metabolism and its possible relationship with the FGF21 signaling
      pathway in diabetic Goto-Kakizaki (GK) rats. Methods: Ten-week-old male GK rats
      were subjected to IT surgery with translocation of a 10 cm ileal segment to the
      proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham
      IT group). Rats in the no surgery group did not receive any surgical
      intervention. Six weeks later, body weight, fat mass, fasting blood glucose
      (FBG), and serum levels of FGF21 and leptin were measured. The expression of the
      FGF21 signaling pathway and white adipose tissue (WAT) browning-related genes in
      the WAT and liver were evaluated by real-time reverse transcription polymerase
      chain reaction (RT-qPCR) and western blot. Results: IT surgery significantly
      decreased the body weights and FBG levels and increased the insulin sensitivity
      of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared
      with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats
      decreased by 26.3 and 61.7%, respectively (all P < 0.05). The mRNA levels of
      fibroblast growth factor receptor 1 (FGFR1) and its co-receptor beta klotho (KLB)
      in the perirenal WAT (pWAT) of the IT rats were 1.4- and 2.4-fold that of the
      Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the
      Sham-IT rats (all P < 0.05). In accordance with the pWAT, the protein levels of
      FGFR1 and KLB in the epididymal WAT (eWAT) of the IT rats notably increased to
      3.0- and 3.9-fold of the Sham-IT rats (P < 0.05). Furthermore, uncoupling protein
      1 (UCP1) protein levels in the eWAT and pWAT of the IT rats also increased to 2.2
      and 2.3-fold of the Sham-IT rats (P < 0.05). However, the protein levels of
      FGFR1 and KLB in the subcutaneous WAT (sWAT) of the IT rats decreased by 34.4 and
      72.1%, respectively, compared with the Sham-IT rats (P < 0.05). In addition, the
      protein levels of FGF21 and KLB in the livers of IT rats were 3.9- and 2.3-fold
      of the Sham-IT rats (all P < 0.05). Conclusions: IT surgery significantly
      decreased fat mass and improved glucose metabolism in diabetic GK rats. These
      beneficial roles of IT surgery were probably associated with its stimulatory
      action on the expression of FGFR1 and KLB in both the eWAT and the pWAT, thereby
      promoting UCP1 expression in these tissues.

PMID- 29593556
TI  - Hypoglycemia: Role of Hypothalamic Glucose-Inhibited (GI) Neurons in Detection
      and Correction.
AB  - Hypoglycemia is a profound threat to the brain since glucose is its primary fuel.
      As a result, glucose sensors are widely located in the central nervous system and
      periphery. In this perspective we will focus on the role of hypothalamic glucose
      inhibited (GI) neurons in sensing and correcting hypoglycemia. In particular, we
      will discuss GI neurons in the ventromedial hypothalamus (VMH) which express
      neuronal nitric oxide synthase (nNOS) and in the perifornical hypothalamus (PFH)
      which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low
      glucose closely parallels the hormonal response to hypoglycemia which stimulates
      gluconeogenesis. We have found that nitric oxide (NO) production in low glucose
      is dependent on oxidative status. In this perspective we will discuss the
      potential relevance of our work showing that enhancing the glutathione
      antioxidant system prevents hypoglycemia associated autonomic failure (HAAF) in
      non-diabetic rats whereas VMH overexpression of the thioredoxin antioxidant
      system restores hypoglycemia counterregulation in rats with type 1 diabetes.We
      will also address the potential role of the orexin-GI neurons in the arousal
      response needed for hypoglycemia awareness which leads to behavioral correction
      (e.g., food intake, glucose administration). The potential relationship between
      the hypothalamic sensors and the neurocircuitry in the hindbrain and portal
      mesenteric vein which is critical for hypoglycemia correction will then be
      discussed.

PMID- 29593557
TI  - 3,5-Diiodo-L-Thyronine Affects Structural and Metabolic Features of Skeletal
      Muscle Mitochondria in High-Fat-Diet Fed Rats Producing a Co-adaptation to the
      Glycolytic Fiber Phenotype.
AB  - Hyperlipidemic state-associated perturbations in the network of factors
      controlling mitochondrial functions, i. e., morphogenesis machinery and metabolic
      sensor proteins, produce metabolic inflexibility, insulin resistance and reduced
      oxidative capacity in skeletal muscle. Moreover, intramyocellular lipid (IMCL)
      accumulation leads to tissue damage and inflammation. The administration of the
      naturally occurring metabolite 3,5-diiodo-L-thyronine (T2) with thyromimetic
      actions to high fat diet (HFD)-fed rats exerts a systemic hypolipidemic effect,
      which produces a lack of IMCL accumulation, a shift toward glycolytic fibers and
      amelioration of insulin sensitivity in gastrocnemius muscle. In this study, an
      integrated approach combining large-scale expression profile and functional
      analyses was used to characterize the response of skeletal muscle mitochondria to
      T2 during a HFD regimen. Long-term T2 administration to HDF rats induced a
      glycolytic phenotype of gastrocnemius muscle as well as an adaptation of
      mitochondria to the fiber type, with a decreased representation of enzymes
      involved in mitochondrial oxidative metabolism. At the same time, T2 stimulated
      the activity of individual respiratory complex I, IV, and V. Moreover, T2
      prevented the HFD-associated increase in the expression of peroxisome
      proliferative activated receptor gamma coactivator-1alpha and dynamin-1-like
      protein as well as mitochondrial morphological aberrations, favoring the
      appearance of tubular and tethered organelles in the intermyofibrillar regions.
      Remarkably, T2 reverted the HDF-associated expression pattern of proinflammatory
      factors, such as p65 subunit of NF-kB, and increased the fiber-specific
      immunoreactivity of adipose differentiation-related protein in lipid droplets.
      All together, these results further support a role of T2 in counteracting in vivo
      some of the HFD-induced impairment in structural/metabolic features of skeletal
      muscle by impacting the mitochondrial phenotype.

PMID- 29593558
TI  - An Individualized, Perception-Based Protocol to Investigate Human Physiological
      Responses to Cooling.
AB  - Cold exposure, a known stimulant of the thermogenic effects of brown adipose
      tissue (BAT), is the most widely used method to study BAT physiology in adult
      humans. Recently, individualized cooling has been recommended to standardize the
      physiological cold stress applied across participants, but critical experimental
      details remain unclear. The purpose of this work was to develop a detailed
      methodology for an individualized, perception-based protocol to investigate human
      physiological responses to cooling. Participants were wrapped in two water
      circulating blankets and fitted with skin temperature probes to estimate BAT
      activity and peripheral vasoconstriction. We created a thermoesthesia graphical
      user interface (tGUI) to continuously record the subject's perception of cooling
      and shivering status during the cooling protocol. The protocol began with a 15
      min thermoneutral phase followed by a series of 10 min cooling phases and
      concluded when sustained shivering (>1 min duration) occurred. Researchers used
      perception of cooling feedback (tGUI ratings) to manually adjust and personalize
      the water temperature at each cooling phase. Blanket water temperatures were
      recorded continuously during the protocol. Twelve volunteers (ages: 26.2 +/- 1.4
      years; 25% female) completed a feasibility study to evaluate the proposed
      protocol. Water temperature, perception of cooling, and shivering varied
      considerably across participants in response to cooling. Mean clavicle skin
      temperature, a surrogate measure of BAT activity, decreased (-0.99 degrees C, 95%
      CI: -1.7 to -0.25 degrees C, P = 0.16) after the cooling protocol, but an
      increase in supraclavicular skin temperature was observed in 4 participants. A
      strong positive correlation was also found between thermoesthesia and peripheral
      vasoconstriction (rho = 0.84, P < 0.001). The proposed individualized, perception
      based protocol therefore has potential to investigate the physiological responses
      to cold stress applied across populations with varying age, sex, body
      composition, and cold sensitivity characteristics.

PMID- 29593559
TI  - Ghrelin Pre-treatment Attenuates Local Oxidative Stress and End Organ Damage
      During Cardiopulmonary Bypass in Anesthetized Rats.
AB  - Cardiopulmonary bypass (CPB) induced systemic inflammation significantly
      contributes to the development of postoperative complications, including
      respiratory failure, myocardial, renal and neurological dysfunction and
      ultimately can lead to failure of multiple organs. Ghrelin is a small endogenous
      peptide with wide ranging physiological effects on metabolism and cardiovascular
      regulation. Herein, we investigated the protective effects of ghrelin against CPB
      induced inflammatory reactions, oxidative stress and acute organ damage. Adult
      male Sprague Dawley rats randomly received vehicle (n = 5) or a bolus of ghrelin
      (150 MUg/kg, sc, n = 5) and were subjected to CPB for 4 h (protocol 1). In
      separate rats, ghrelin pre-treatment (protocol 2) was compared to two doses of
      ghrelin (protocol 3) before and after CPB for 2 h followed by recovery for 2 h.
      Blood samples were taken prior to CPB, and following CPB at 2 h and 4 h. Organ
      nitrosative stress (3-nitrotyrosine) was measured by Western blotting. CPB
      induced leukocytosis with increased plasma levels of tumor necrosis factor-alpha
      and interleukin-6 indicating a potent inflammatory response. Ghrelin treatment
      significantly reduced plasma organ damage markers (lactate dehydrogenase,
      aspartate aminotransferase, alanine aminotransferase) and protein levels of 3
      nitrotyrosine, particularly in the brain, lung and liver, but only partly
      suppressed inflammatory cell invasion and did not reduce proinflammatory cytokine
      production. Ghrelin partially attenuated the CPB-induced elevation of epinephrine
      and to a lesser extent norepinephrine when compared to the CPB saline group,
      while dopamine levels were completely suppressed. Ghrelin treatment sustained
      plasma levels of reduced glutathione and decreased glutathione disulphide when
      compared to CPB saline rats. These results suggest that even though ghrelin only
      partially inhibited the large CPB induced increase in catecholamines and organ
      macrophage infiltration, it reduced oxidative stress and subsequent cell damage.
      Pre-treatment with ghrelin might provide an effective adjunct therapy for
      preventing widespread CPB induced organ injury.

PMID- 29593560
TI  - Intestinal Metagenomes and Metabolomes in Healthy Young Males: Inactivity and
      Hypoxia Generated Negative Physiological Symptoms Precede Microbial Dysbiosis.
AB  - We explored the metagenomic, metabolomic and trace metal makeup of intestinal
      microbiota and environment in healthy male participants during the run-in (5 day)
      and the following three 21-day interventions: normoxic bedrest (NBR), hypoxic
      bedrest (HBR) and hypoxic ambulation (HAmb) which were carried out within a
      controlled laboratory environment (circadian rhythm, fluid and dietary intakes,
      microbial bioburden, oxygen level, exercise). The fraction of inspired O2 (FiO2)
      and partial pressure of inspired O2 (PiO2) were 0.209 and 133.1 +/- 0.3 mmHg for
      the NBR and 0.141 +/- 0.004 and 90.0 +/- 0.4 mmHg (~4,000 m simulated altitude)
      for HBR and HAmb interventions, respectively. Shotgun metagenomes were analyzed
      at various taxonomic and functional levels, 1H- and 13C -metabolomes were
      processed using standard quantitative and human expert approaches, whereas metals
      were assessed using X-ray fluorescence spectrometry. Inactivity and hypoxia
      resulted in a significant increase in the genus Bacteroides in HBR, in genes
      coding for proteins involved in iron acquisition and metabolism, cell wall,
      capsule, virulence, defense and mucin degradation, such as beta-galactosidase
      (EC3.2.1.23), alpha-L-fucosidase (EC3.2.1.51), Sialidase (EC3.2.1.18), and alpha
      N-acetylglucosaminidase (EC3.2.1.50). In contrast, the microbial metabolomes,
      intestinal element and metal profiles, the diversity of bacterial, archaeal and
      fungal microbial communities were not significantly affected. The observed
      progressive decrease in defecation frequency and concomitant increase in the
      electrical conductivity (EC) preceded or took place in absence of significant
      changes at the taxonomic, functional gene, metabolome and intestinal metal
      profile levels. The fact that the genus Bacteroides and proteins involved in iron
      acquisition and metabolism, cell wall, capsule, virulence and mucin degradation
      were enriched at the end of HBR suggest that both constipation and EC decreased
      intestinal metal availability leading to modified expression of co-regulated
      genes in Bacteroides genomes. Bayesian network analysis was used to derive the
      first hierarchical model of initial inactivity mediated deconditioning steps over
      time. The PlanHab wash-out period corresponded to a profound life-style change
      (i.e., reintroduction of exercise) that resulted in stepwise amelioration of the
      negative physiological symptoms, indicating that exercise apparently prevented
      the crosstalk between the microbial physiology, mucin degradation and
      proinflammatory immune activities in the host.

PMID- 29593561
TI  - Reciprocal Interactions of Mitochondria and the Neuroimmunoendocrine System in
      Neurodegenerative Disorders: An Important Role for Melatonin Regulation.
AB  - Structural and functional alterations of mitochondria are intimately linked to a
      wide array of medical conditions. Many factors are involved in the regulation of
      mitochondrial function, including cytokines, chaperones, chemokines,
      neurosteroids, and ubiquitins. The role of diffusely located cells of the
      neuroendocrine system, including biogenic amines and peptide hormones, in the
      management of mitochondrial function, as well as the role of altered
      mitochondrial function in the regulation of these cells and system, is an area of
      intense investigation. The current article looks at the interactions among the
      cells of the neuronal-glia, immune and endocrine systems, namely the diffuse
      neuroimmunoendocrine system (DNIES), and how DNIES interacts with mitochondrial
      function. Whilst changes in DNIES can impact on mitochondrial function, local,
      and systemic alterations in mitochondrial function can alter the component
      systems of DNIES and their interactions. This has etiological, course, and
      treatment implications for a wide range of medical conditions, including
      neurodegenerative disorders. Available data on the role of melatonin in these
      interactions, at cellular and system levels, are reviewed, with directions for
      future research indicated.

PMID- 29593563
TI  - Whole-Body Vibrations Associated With Alpine Skiing: A Risk Factor for Low Back
      Pain?
AB  - Alpine skiing, both recreational and competitive, is associated with high rates
      of injury. Numerous studies have shown that occupational exposure to whole-body
      vibrations is strongly related to lower back pain and some suggest that, in
      particular, vibrations of lower frequencies could lead to overuse injuries of the
      back in connection with alpine ski racing. However, it is not yet known which
      forms of skiing involve stronger vibrations and whether these exceed safety
      thresholds set by existing standards and directives. Therefore, this study was
      designed to examine whole-body vibrations connected with different types of
      skiing and the associated potential risk of developing low back pain. Eight
      highly skilled ski instructors, all former competitive ski racers and equipped
      with five accelerometers and a Global Satellite Navigation System to measure
      vibrations and speed, respectively, performed six different forms of skiing:
      straight running, plowing, snow-plow swinging, basic swinging, short swinging,
      and carved turns. To estimate exposure to periodic, random and transient
      vibrations the power spectrum density (PSD) and standard ISO 2631-1:1997
      parameters [i.e., the weighted root-mean-square acceleration (RMS), crest factor,
      maximum transient vibration value and the fourth-power vibration dose value
      (VDV)] were calculated. Ground reaction forces were estimated from data provided
      by accelerometers attached to the pelvis. The major novel findings were that all
      of the forms of skiing tested produced whole-body vibrations, with highest PSD
      values of 1.5-8 Hz. Intensified PSD between 8.5 and 35 Hz was observed only when
      skidding was involved. The RMS values for 10 min of short swinging or carved
      turns, as well as all 10-min equivalent VDV values exceeded the limits set by
      European Directive 2002/44/EC for health and safety. Thus, whole-body vibrations,
      particularly in connection with high ground reaction forces, contribute to a high
      risk for low back pain among active alpine skiers.

PMID- 29593562
TI  - Toll-Like Receptors, Inflammation, and Calcific Aortic Valve Disease.
AB  - Inflammation, the primary response of innate immunity, is essential to initiate
      the calcification process underlying calcific aortic valve disease (CAVD), the
      most prevalent valvulopathy in Western countries. The pathogenesis of CAVD is
      multifactorial and includes inflammation, hemodynamic factors, fibrosis, and
      active calcification. In the development of CAVD, both innate and adaptive immune
      responses are activated, and accumulating evidences show the central role of
      inflammation in the initiation and propagation phases of the disease, being the
      function of Toll-like receptors (TLR) particularly relevant. These receptors act
      as sentinels of the innate immune system by recognizing pattern molecules from
      both pathogens and host-derived molecules released after tissue damage. TLR
      mediate inflammation via NF-kappaB routes within and beyond the immune system,
      and play a crucial role in the control of infection and the maintenance of tissue
      homeostasis. This review outlines the current notions about the association
      between TLR signaling and the ensuing development of inflammation and
      fibrocalcific remodeling in the pathogenesis of CAVD. Recent data provide new
      insights into the inflammatory and osteogenic responses underlying the disease
      and further support the hypothesis that inflammation plays a mechanistic role in
      the initiation and progression of CAVD. These findings make TLR signaling a
      potential target for therapeutic intervention in CAVD.

PMID- 29593564
TI  - Dynamic Action Potential Restitution Contributes to Mechanical Restitution in
      Right Ventricular Myocytes From Pulmonary Hypertensive Rats.
AB  - We investigated the steepened dynamic action potential duration (APD) restitution
      of rats with pulmonary artery hypertension (PAH) and right ventricular (RV)
      failure and tested whether the observed APD restitution properties were
      responsible for negative mechanical restitution in these myocytes. PAH and RV
      failure were provoked in male Wistar rats by a single injection of monocrotaline
      (MCT) and compared with saline-injected animals (CON). Action potentials were
      recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz.
      Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles
      (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke
      rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD
      restitution were applied and cell shortening simultaneously monitored. Compared
      with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic
      membrane potentials; had action potentials that were triggered by decreased
      positive current density and shortened by decreased negative current density; APD
      was longer and APD restitution steeper. APD90 restitution was unchanged by
      exposure to the late Na+-channel blocker (5 MUM) ranolazine or the intracellular
      Ca2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward
      currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT
      myocytes, increasing stimulation frequency decreased contraction amplitude when
      depolarization duration was shortened, to mimic APD restitution, but not when
      depolarization duration was maintained. We present new evidence that the membrane
      potential of PAH myocytes is less stable than normal myocytes, being more easily
      perturbed by external currents. These observations can explain increased
      susceptibility to arrhythmias. We also present novel evidence that negative APD
      restitution is at least in part responsible for the negative mechanical
      restitution in PAH myocytes. Thus, our study links electrical restitution
      remodeling to a defining mechanical characteristic of heart failure, the reduced
      ability to respond to an increase in demand.

PMID- 29593565
TI  - Aerobic Interval Training Prevents Age-Dependent Vulnerability to Atrial
      Fibrillation in Rodents.
AB  - Aims: Increasing age is the most important risk factor for atrial fibrillation
      (AF). Very high doses of exercise training might increase AF risk, while moderate
      levels seem to be protective. This study aimed to examine the effects of age on
      vulnerability to AF and whether long-term aerobic interval training (AIT) could
      modify these effects. Methods: Nine months old, male Sprague-Dawley rats were
      randomized to AIT for 16 weeks (old-ex) or to a sedentary control group (old
      sed), and compared to young sedentary males (young-sed). After the intervention,
      animals underwent echocardiography, testing of exercise capacity (VO2max), and
      electrophysiology with AF induction before ex vivo electrophysiology. Fibrosis
      quantification, immunohistochemistry and western blotting of atrial tissue were
      performed. Results: Sustained AF was induced in vivo in 4 of 11 old-sed animals,
      but none of the old-ex or young-sed rats (p = 0.006). VO2max was lower in old
      sed, while old-ex had comparable results to young-sed. Fibrosis was increased in
      old-sed (p = 0.006), with similar results in old-ex. There was a significantly
      slower atrial conduction in old-sed (p = 0.038), with an increase in old-ex (p =
      0.027). Action potential duration was unaltered in old-sed, but prolonged in old
      ex (p = 0.036). There were no differences in amount of atrial connexin 43 between
      groups, but a lateralization in atrial cardiomyocytes of old-sed, with similar
      findings in old-ex. Conclusion: AF vulnerability was higher in old-sed animals,
      associated with increased atrial fibrosis, lateralization of connexin-43, and
      reduced atrial conduction velocity. AIT reduced the age-associated susceptibility
      to AF, possibly through increased conduction velocity and prolongation of action
      potentials.

PMID- 29593566
TI  - Real-Time Rotational Activity Detection in Atrial Fibrillation.
AB  - Rotational activations, or spiral waves, are one of the proposed mechanisms for
      atrial fibrillation (AF) maintenance. We present a system for assessing the
      presence of rotational activity from intracardiac electrograms (EGMs). Our system
      is able to operate in real-time with multi-electrode catheters of different
      topologies in contact with the atrial wall, and it is based on new local
      activation time (LAT) estimation and rotational activity detection methods. The
      EGM LAT estimation method is based on the identification of the highest sustained
      negative slope of unipolar signals. The method is implemented as a linear filter
      whose output is interpolated on a regular grid to match any catheter topology.
      Its operation is illustrated on selected signals and compared to the classical
      Hilbert-Transform-based phase analysis. After the estimation of the LAT on the
      regular grid, the detection of rotational activity in the atrium is done by a
      novel method based on the optical flow of the wavefront dynamics, and a rotation
      pattern match. The methods have been validated using in silico and real AF
      signals.

PMID- 29593567
TI  - Kisspeptin Receptor GPR54 Promotes Adipocyte Differentiation and Fat Accumulation
      in Mice.
AB  - GPR54, Kisspeptin-1 receptor (KISS1R), a member of rhodopsin family, plays a
      critical role in puberty development and has been proposed to be involved in
      regulation of energy metabolism. This study aims to explore the function of GPR54
      in adipogenesis, lipid metabolism, and obesity in addition to its effect through
      hormones. Results showed that when fed a high-fat diet, the weight growth of
      castrated or ovariectomized Gpr54-/- mice was significantly slower than that of
      WT control, together with a lower triglyceride concentration. The ratio of white
      adipose tissue was lower, and average size of adipocytes was smaller in Gpr54-/-
      mice. Meanwhile, there were less adipose tissue macrophages (ATMs), especially
      pro-inflammatory macrophages. Expression of inflammatory related genes also
      indicated that inflammatory response caused by obesity was not as drastic in
      Gpr54-/- mice as in WT mice. Liver triglyceride in Gpr54-/- mice was reduced,
      especially in female mice. On the other hand, oil drop formation was accelerated
      when hepatocytes were stimulated by kisspeptin-10 (Kp-10). Primary mesenchymal
      stem cells (MSCs) of Gpr54-/- mice were less likely to differentiate into
      adipocytes. When stimulated by Kp-10, 3T3-L1 cell differentiation into adipocytes
      was accelerated and triglyceride synthesis was significantly promoted. These data
      indicated that GPR54 could affect obesity development by promoting adipocyte
      differentiation and triglyceride accumulation. To further elucidate the
      mechanism, genes related to lipid metabolism were analyzed. The expression of
      genes involved in lipid synthesis including PPARgamma, ACC1, ADIPO, and FAS was
      significantly changed in Gpr54-/- mice. Among them PPARgamma which also
      participate in adipocyte differentiation displayed a marked reduction. Moreover,
      phosphorylation of ERK, which involved in GPR54 signaling, was significantly
      decreased in Gpr54-/- mice, suggesting that GPR54 may promote lipid synthesis and
      obesity development by activating MAP kinase pathway. Therefore, in addition to
      the involvement in hormone regulation, our study demonstrated that GPR54 directly
      participates in obesity development by promoting adipocyte differentiation and
      fat accumulation. This provided evidence of involvement of GPR54 in lipid
      metabolism, and revealed new potentials for the identification and development of
      novel drug targets for metabolic diseases.

PMID- 29593568
TI  - Bisecting N-Acetylglucosamine Structures Inhibit Hypoxia-Induced Epithelial
      Mesenchymal Transition in Breast Cancer Cells.
AB  - The epithelial-mesenchymal transition (EMT) process plays a key role in many
      biological processes, including tissue fibrosis, metastatic diseases, and cancer
      progression. EMT can be induced by certain factors, notably hypoxia, in the tumor
      microenvironment. Aberrant levels of certain N-glycans is associated with cancer
      progression. We used an integrated strategy (mass spectrometry in combination
      with lectin microarray analysis) to elucidate aberrant glycosylation in a hypoxia
      induced EMT model using breast cancer cell lines MCF7 and MDA-MB-231. The model
      showed reduced levels of bisecting GlcNAc structures, and downregulated
      expression of the corresponding glycosyltransferase MGAT3. MGAT3 overexpression
      in MCF7 suppressed cell migration, proliferation, colony formation, expression of
      EMT markers, and AKT signaling pathway, whereas MGAT3 knockdown (shRNA silencing)
      had opposite effects. Our findings clearly demonstrate the functional role (and
      effects of dysregulation) of bisecting GlcNAc structures in hypoxia-induced EMT,
      and provide a useful basis for further detailed studies of physiological
      functions of these structures in breast cancer.

PMID- 29593569
TI  - Spatial mRNA Expression and Response to Fasting and Refeeding of Neutral Amino
      Acid Transporters slc6a18 and slc6a19a in the Intestinal Epithelium of Mozambique
      tilapia.
AB  - The mRNA expressions of the epithelial neutral amino acid transporters slc6a18
      and slc6a19a in the five segments (HL, PMC, GL, DMC, and TS) of the intestine of
      Mozambique tilapia, and their responses to fasting and refeeding were
      investigated for a better understanding of the functional and nutritional
      characteristics of slc6a18 and slc6a19a. Although both slc6a18 and slc6a19a were
      expressed mainly in the intestine, these genes showed opposing spatial
      distributions along the intestine. The slc6a18 was mainly expressed in the middle
      (GL) and posterior (DMC and TS) intestines, while slc6a19a was specifically
      expressed in the anterior intestine (HL and PMC). Large decreases of amino acid
      concentrations from the HL to GL imply that amino acids are mainly absorbed
      before reaching the GL, suggesting an important role of slc6a19a in the
      absorption. Moreover, substantial amounts of some neutral amino acids with the
      isoelectric point close to 6 remain in the GL. These are most likely the
      remaining unabsorbed amino acids or those from of amino acid antiporters which
      release neutral amino acids in exchange for uptake of its substrates. These amino
      acids were diminished in the TS, suggesting active absorption in the posterior
      intestine. This suggests that slc6a18 is essential to complete the absorption of
      neutral amino acids. At fasting, significant downregulation of slc6a19a
      expression was observed from the initial up to day 2 and became stable from day 4
      to day 14 in the HL and PMC suggesting that slc6a19a expression reflects
      nutritional condition in the intestinal lumen. Refeeding stimulates slc6a19a
      expression, although expressions did not exceed the initial level within 3 days
      after refeeding. The slc6a18 expression was decreased during fasting in the GL
      but no significant change was observed in the DMC. Only a transient decrease was
      observed at day 2 in the TS. Refeeding did not stimulate slc6a18 expression.
      Results in this study suggest that Slc6a18 and Slc6a19 have different roles in
      the intestine, and that both of these contribute to establish the efficient
      neutral amino acid absorption system in the tilapia.

PMID- 29593570
TI  - Distinct ECG Phenotypes Identified in Hypertrophic Cardiomyopathy Using Machine
      Learning Associate With Arrhythmic Risk Markers.
AB  - Aims: Ventricular arrhythmia triggers sudden cardiac death (SCD) in hypertrophic
      cardiomyopathy (HCM), yet electrophysiological biomarkers are not used for risk
      stratification. Our aim was to identify distinct HCM phenotypes based on ECG
      computational analysis, and characterize differences in clinical risk factors and
      anatomical differences using cardiac magnetic resonance (CMR) imaging. Methods:
      High-fidelity 12-lead Holter ECGs from 85 HCM patients and 38 healthy volunteers
      were analyzed using mathematical modeling and computational clustering to
      identify phenotypic subgroups. Clinical features and the extent and distribution
      of hypertrophy assessed by CMR were evaluated in the subgroups. Results: QRS
      morphology alone was crucial to identify three HCM phenotypes with very distinct
      QRS patterns. Group 1 (n = 44) showed normal QRS morphology, Group 2 (n = 19)
      showed short R and deep S waves in V4, and Group 3 (n = 22) exhibited short R and
      long S waves in V4-6, and left QRS axis deviation. However, no differences in
      arrhythmic risk or distribution of hypertrophy were observed between these
      groups. Including T wave biomarkers in the clustering, four HCM phenotypes were
      identified: Group 1A (n = 20), with primary repolarization abnormalities showing
      normal QRS yet inverted T waves, Group 1B (n = 24), with normal QRS morphology
      and upright T waves, and Group 2 and Group 3 remaining as before, with upright T
      waves. Group 1A patients, with normal QRS and inverted T wave, showed increased
      HCM Risk-SCD scores (1A: 4.0%, 1B: 1.8%, 2: 2.1%, 3: 2.5%, p = 0.0001), and a
      predominance of coexisting septal and apical hypertrophy (p < 0.0001). HCM
      patients in Groups 2 and 3 exhibited predominantly septal hypertrophy (85 and
      90%, respectively). Conclusion: HCM patients were classified in four subgroups
      with distinct ECG features. Patients with primary T wave inversion not secondary
      to QRS abnormalities had increased HCM Risk-SCD scores and coexisting septal and
      apical hypertrophy, suggesting that primary T wave inversion may increase SCD
      risk in HCM, rather than T wave inversion secondary to depolarization
      abnormalities. Computational ECG phenotyping provides insight into the underlying
      processes captured by the ECG and has the potential to be a novel and independent
      factor for risk stratification.

PMID- 29593571
TI  - Mechanistic Role of Reactive Oxygen Species and Therapeutic Potential of
      Antioxidants in Denervation- or Fasting-Induced Skeletal Muscle Atrophy.
AB  - Skeletal muscle atrophy occurs under various conditions, such as disuse,
      denervation, fasting, aging, and various diseases. Although the underlying
      molecular mechanisms are still not fully understood, skeletal muscle atrophy is
      closely associated with reactive oxygen species (ROS) overproduction. In this
      study, we aimed to investigate the involvement of ROS in skeletal muscle atrophy
      from the perspective of gene regulation, and further examine therapeutic effects
      of antioxidants on skeletal muscle atrophy. Microarray data showed that the gene
      expression of many positive regulators for ROS production were up-regulated and
      the gene expression of many negative regulators for ROS production were down
      regulated in mouse soleus muscle atrophied by denervation (sciatic nerve injury).
      The ROS level was significantly increased in denervated mouse soleus muscle or
      fasted C2C12 myotubes that had suffered from fasting (nutrient deprivation).
      These two muscle samples were then treated with N-acetyl-L-cysteine (NAC, a
      clinically used antioxidant) or pyrroloquinoline quinone (PQQ, a naturally
      occurring antioxidant), respectively. As compared to non-treatment, both NAC and
      PQQ treatment (1) reversed the increase in the ROS level in two muscle samples;
      (2) attenuated the reduction in the cross-sectional area (CSA) of denervated
      mouse muscle or in the diameter of fasted C2C12 myotube; (3) increased the myosin
      heavy chain (MHC) level and decreased the muscle atrophy F-box (MAFbx) and muscle
      specific RING finger-1 (MuRF-1) levels in two muscle samples. Collectively, these
      results suggested that an increased ROS level was, at least partly, responsible
      for denervation- or fasting-induced skeletal muscle atrophy, and antioxidants
      might resist the atrophic effect via ROS-related mechanisms.

PMID- 29593572
TI  - Identification of Exosomal miRNAs in Rats With Pulmonary Neutrophilic
      Inflammation Induced by Zinc Oxide Nanoparticles.
AB  - It has been previously shown that inhaled zinc oxide nanoparticles (ZnO-NPs) can
      modulate inflammation. MicroRNAs (miRNAs) enclosed in exosomes have been
      identified as an important signature for inflammatory responses. However, the
      role of exosomal miRNAs during pathogenic inflammation has not been investigated.
      Healthy rats were exposed to ZnO-NPs (41.7 nm; 2, 4, and 8 mg/kg) or saline
      (control) via oropharyngeal aspiration. ZnO-NPs induced significant increases in
      the serum levels of interleukin 8 (IL-8), interleukin-1 beta (IL-1beta), and
      tumor necrosis factor alpha (TNF-alpha), and elevated the number of cells and the
      percentage of neutrophils in the blood. Moreover, exposure to ZnO-NPs increased
      the levels of lactate dehydrogenase (LDH) activity and total protein in
      bronchoalveolar lavage fluid (BALF). Differential profiling of miRNAs in isolated
      serum exosomes revealed that 16 miRNAs were up-regulated and 7 down-regulated in
      ZnO-NP-treated rats compared with the controls. Functional and pathway analysis
      indicated that miRNAs may participate in inflammation directly and indirectly
      through protein and vesicle-mediated transport or regulation of IL-1, oxidative
      stress, apoptosis, and autophagy. These results suggest that miRNAs in serum
      exosomes are involved in pulmonary neutrophilic inflammation induced by ZnO-NPs.

PMID- 29593573
TI  - Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice
      Models.
AB  - The prevalence of non-alcoholic fatty liver disease (NAFLD), which is developed
      from hepatic steatosis, is increasing worldwide. However, no specific drugs for
      NAFLD have been approved yet. To observe the effects of Rho, a fraction from
      Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with
      characteristics of NAFLD were used including high-fat diet (HFD)-induced obesity
      (DIO) mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T
      mice. Hepatic lipid accumulation was determined via histopathological analysis
      and/or hepatic TG determination. The responses to insulin were evaluated by
      insulin tolerance test (ITT), glucose tolerance test (GTT), and hyperinsulinemic
      euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism
      were observed via western-blot. Furthermore, the liver microcirculation was
      observed by inverted microscopy. The HPLC analysis indicated that the main
      components of Rho were flavan polymers. The results of histopathological analysis
      showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T
      hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice,
      insulin resistance was improved with increasing glucose infusion rate (GIR) in
      hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose
      time curve (AUC) in both ITT and GTT; the pathways involved in fatty acid uptake
      and de novo lipogenesis were both down-regulated, respectively. However, the
      pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not
      changed significantly. The liver microcirculation disturbances were also improved
      by Rho in DIO mice. These results suggest that Rho is a lead nature product for
      hepatic steatosis treatment. The mechanism is related to enhancing insulin
      sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in
      liver.

PMID- 29593574
TI  - The Use of Biophysical Flow Models in the Surgical Management of Patients
      Affected by Chronic Thromboembolic Pulmonary Hypertension.
AB  - Introduction: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) results from
      progressive thrombotic occlusion of the pulmonary arteries. It is treated by
      surgical removal of the occlusion, with success rates depending on the degree of
      microvascular remodeling. Surgical eligibility is influenced by the contributions
      of both the thrombus occlusion and microvasculature remodeling to the overall
      vascular resistance. Assessing this is challenging due to the high inter
      individual variability in arterial morphology and physiology. We investigated the
      potential of patient-specific computational flow modeling to quantify pressure
      gradients in the pulmonary arteries of CTEPH patients to assist the decision
      making process for surgical eligibility. Methods: Detailed segmentations of the
      pulmonary arteries were created from postoperative chest Computed Tomography
      scans of three CTEPH patients. A focal stenosis was included in the original
      geometry to compare the pre- and post-surgical hemodynamics. Three-dimensional
      flow simulations were performed on each morphology to quantify velocity-dependent
      pressure changes using a finite element solver coupled to terminal 2-element
      Windkessel models. In addition to transient flow simulations, a parametric
      modeling approach based on constant flow simulations is also proposed as faster
      technique to estimate relative pressure drops through the proximal pulmonary
      vasculature. Results: An asymmetrical flow split between left and right pulmonary
      arteries was observed in the stenosed models. Removing the proximal obstruction
      resulted in a reduction of the right-left pressure imbalance of up to 18%.
      Changes were also observed in the wall shear stresses and flow topology, where
      vortices developed in the stenosed model while the non-stenosed retained a
      helical flow. The predicted pressure gradients from constant flow simulations
      were consistent with the ones measured in the transient flow simulations.
      Conclusion: This study provides a proof of concept that patient-specific
      computational modeling can be used as a noninvasive tool for assisting surgical
      decisions in CTEPH based on hemodynamics metrics. Our technique enables
      determination of the proximal relative pressure, which could subsequently be
      compared to the total pressure drop to determine the degree of distal and
      proximal vascular resistance. In the longer term this approach has the potential
      to form the basis for a more quantitative classification system of CTEPH types.

PMID- 29593575
TI  - Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin
      Resistance in db/db Mice.
AB  - Intricate health problems, such as insulin resistance (IR) and its associated
      diseases, call for multi-targeted therapies with few side effects. Based on
      traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula
      mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus
      (Zhishi), of which berberine and naringin are the main constituents. Though DZF
      has been clinically used for treatment of IR and metabolic syndrome for decades,
      its mechanism in vivo remains unknown. In the present study, we observed that
      both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated
      insulin resistance with significant improvement of oral glucose tolerance test
      (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic
      C57BL/Ksj-Lepr db-/- (db/db) mice. Low-density lipoprotein cholesterol (LDL-C)
      and fatty acids (FAs) also decreased in the blood. Higher dose of DZF (1 g.kg-1),
      but not metformin (0.25 g.kg-1), alleviated hepatic steatosis with reduced liver
      weight and hepatic lipid accumulation and provided protection from hepatic injury
      with lower alanine aminotransferase and aspartate aminotransferase and increased
      hepatic superoxide dismutase activity in db/db mice. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) showed a decrease in FA
      synthase gene (Fasn) and an increase in FA oxidation gene Ppara expression.
      Western blot demonstrated that both DZF and metformin activated 5' AMP-activated
      protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and
      Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver. DZF
      also dramatically improved the ultrastructure of skeletal muscles, AMPK
      phosphorylation, and GLUT4 translocation. DZF also promoted FA transport and
      oxidation with Cd36 and Cpt1b up-regulation in the skeletal muscle. In
      conclusion, DZF improves insulin sensitivity by reducing hepatic lipids through
      AMPK activation and Notch signal pathway inhibition and enhancing energy
      metabolism in the skeletal muscle via AMPK. This study provides insights into the
      treatment of complex conditions, such as IR, where TCM herbal formulas exert
      multipronged effects through correlating pathways.

PMID- 29593577
TI  - Predicting Medical Students' Current Attitudes Toward Psychiatry, Interest in
      Psychiatry, and Estimated Likelihood of Working in Psychiatry: A Cross-Sectional
      Study in Four European Countries.
AB  - Psychiatry as a medical discipline is becoming increasingly important due to the
      high and increasing worldwide burden associated with mental disorders.
      Surprisingly, however, there is a lack of young academics choosing psychiatry as
      a career. Previous evidence on medical students' perspectives is abundant but has
      methodological shortcomings. Therefore, by attempting to avoid previous
      shortcomings, we aimed to contribute to a better understanding of the predictors
      of the following three outcome variables: current medical students' attitudes
      toward psychiatry, interest in psychiatry, and estimated likelihood of working in
      psychiatry. The sample consisted of N = 1,356 medical students at 45 medical
      schools in Germany and Austria as well as regions of Switzerland and Hungary with
      a German language curriculum. We used snowball sampling via Facebook with a link
      to an online questionnaire as recruitment procedure. Snowball sampling is based
      on referrals made among people. This questionnaire included a German version of
      the Attitudes Toward Psychiatry Scale (ATP-30-G) and further variables related to
      outcomes and potential predictors in terms of sociodemography (e.g., gender) or
      medical training (e.g., curriculum-related experience with psychiatry). Data were
      analyzed by linear mixed models and further regression models. On average,
      students had a positive attitude to and high general interest in, but low
      professional preference for, psychiatry. A neutral attitude to psychiatry was
      partly related to the discipline itself, psychiatrists, or psychiatric patients.
      Female gender and previous experience with psychiatry, particularly curriculum
      related and personal experience, were important predictors of all outcomes.
      Students in the first years of medical training were more interested in pursuing
      psychiatry as a career. Furthermore, the country of the medical school was
      related to the outcomes. However, statistical models explained only a small
      proportion of variance. The findings indicate that particularly curriculum
      related experience is important for determining attitudes toward psychiatry,
      interest in the subject and self-predicted professional career choice. We
      therefore encourage the provision of opportunities for clinical experience by
      psychiatrists. However, further predictor variables need to be considered in
      future studies.

PMID- 29593578
TI  - Mental Disorder-The Need for an Accurate Definition.
AB  - There are several reasons why a definition for mental disorder is essential.
      Among these are not only reasons linked to psychiatry itself as a science
      (nosology, research) but also to ethical, legal, and financial issues. The first
      formal definition of mental disorder resulted from a deep conceptual analysis led
      by Robert Spitzer. It emerged to address several challenges that psychiatry faced
      at the time, namely to serve as the starting point for an atheoretical and
      evidence-based classification of mental disorders, to justify the removal of
      homosexuality from classifications, and to counter the arguments of
      antipsychiatry. This definition has been updated, with some conceptual changes
      that make it depart from the main assumptions of Spitzer's original definition.
      In this article, we intend to review the factors that substantiated the emergence
      of the first formal definition of mental disorder that based all its later
      versions.

PMID- 29593576
TI  - Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory
      Disorders.
AB  - The vagus nerve represents the main component of the parasympathetic nervous
      system, which oversees a vast array of crucial bodily functions, including
      control of mood, immune response, digestion, and heart rate. It establishes one
      of the connections between the brain and the gastrointestinal tract and sends
      information about the state of the inner organs to the brain via afferent fibers.
      In this review article, we discuss various functions of the vagus nerve which
      make it an attractive target in treating psychiatric and gastrointestinal
      disorders. There is preliminary evidence that vagus nerve stimulation is a
      promising add-on treatment for treatment-refractory depression, posttraumatic
      stress disorder, and inflammatory bowel disease. Treatments that target the vagus
      nerve increase the vagal tone and inhibit cytokine production. Both are important
      mechanism of resiliency. The stimulation of vagal afferent fibers in the gut
      influences monoaminergic brain systems in the brain stem that play crucial roles
      in major psychiatric conditions, such as mood and anxiety disorders. In line,
      there is preliminary evidence for gut bacteria to have beneficial effect on mood
      and anxiety, partly by affecting the activity of the vagus nerve. Since, the
      vagal tone is correlated with capacity to regulate stress responses and can be
      influenced by breathing, its increase through meditation and yoga likely
      contribute to resilience and the mitigation of mood and anxiety symptoms.

PMID- 29593579
TI  - Adenosine A2A Receptor Antagonists in Neurodegenerative Diseases: Huge Potential
      and Huge Challenges.

PMID- 29593580
TI  - Self-Reported Visual Perceptual Abnormalities Are Strongly Associated with Core
      Clinical Features in Psychotic Disorders.
AB  - Background: Past studies using the Bonn Scale for the Assessment of Basic
      Symptoms (hereafter, Bonn Scale) have shown that self-reported
      perceptual/cognitive disturbances reveal which persons have or will soon develop
      schizophrenia. Here, we focused specifically on the clinical value of self
      reported visual perceptual abnormalities (VPAs) since they are underexplored and
      have been associated with suicidal ideation, negative symptoms, and objective
      visual dysfunction. Method: Using the 17 Bonn Scale vision items, we cross
      sectionally investigated lifetime occurrence of VPAs in 21 first-episode
      psychosis and 22 chronic schizophrenia/schizoaffective disorder (SZ/SA) patients.
      Relationships were probed between VPAs and illness duration, symptom severity,
      current functioning, premorbid functioning, diagnosis, and age of onset. Results:
      Increased VPAs were associated with: earlier age of onset; more delusions,
      hallucinations, bizarre behavior, and depressive symptoms; and worse premorbid
      social functioning, especially in the childhood and early adolescent phases.
      SZ/SA participants endorsed more VPAs as compared to those with schizophreniform
      or psychotic disorder-NOS, especially in the perception of color, bodies, faces,
      object movement, and double/reversed vision. The range of self-reported VPAs was
      strikingly similar between first-episode and chronic patients and did not depend
      on the type or amount of antipsychotic medication. As a comparative benchmark,
      lifetime occurrence of visual hallucinations did not depend on diagnosis and was
      linked only to poor premorbid social functioning. Conclusion: A brief 17-item
      interview derived from the Bonn Scale is strongly associated with core clinical
      features in schizophrenia. VPAs hold promise for clarifying diagnosis, predicting
      outcome, and guiding neurocognitive investigations.

PMID- 29593581
TI  - Enhanced Amygdala-Striatal Functional Connectivity during the Processing of
      Cocaine Cues in Male Cocaine Users with a History of Childhood Trauma.
AB  - Background and aims: Childhood trauma is associated with increased levels of
      anxiety later in life, an increased risk for the development of substance use
      disorders, and neurodevelopmental abnormalities in the amygdala and
      frontostriatal circuitry. The aim of this study was to investigate the
      (neurobiological) link among childhood trauma, state anxiety, and amygdala
      frontostriatal activity in response to cocaine cues in regular cocaine users.
      Methods: In this study, we included 59 non-treatment seeking regular cocaine
      users and 58 non-drug using controls. Blood oxygenation level-dependent responses
      were measured using functional magnetic resonance imaging while subjects
      performed a cue reactivity paradigm with cocaine and neutral cues.
      Psychophysiological interaction analyses were applied to assess functional
      connectivity between the amygdala and other regions in the brain. Self-report
      questionnaires were used to measure childhood trauma, state anxiety, drug use,
      drug use severity, and craving. Results: Neural activation was increased during
      the presentation of cocaine cues, in a widespread network including the
      frontostriatal circuit and amygdala in cocaine users but not in controls.
      Functional coupling between the amygdala and medial prefrontal cortex was reduced
      in response to cocaine cues, in both cocaine users and controls, which was
      further diminished with increasing state anxiety. Importantly, amygdala-striatal
      connectivity was positively associated with childhood trauma in regular cocaine
      users, while there was a negative association in controls. At the behavioral
      level, state anxiety was positively associated with cocaine use severity and
      craving related to negative reinforcement. Conclusion: Childhood trauma is
      associated with enhanced amygdala-striatal connectivity during cocaine cue
      reactivity in regular cocaine users, which may contribute to increased habit
      behavior and poorer cognitive control. While we cannot draw conclusions on
      causality, this study provides novel information on how childhood trauma may
      contribute to the development and persistence of cocaine use disorder.

PMID- 29593583
TI  - Attachment to Parents As a Moderator in the Association between Sibling Bullying
      and Depression or Suicidal Ideation among Children and Adolescents.
AB  - Bullying is one of the most widespread phenomenon in childhood and adolescence.
      Interestingly, most research on bullying focuses on bullying at school and not on
      bullying among siblings at home. Sibling bullying is the most frequent form of
      repeated aggression that children experience in their lifetime. Furthermore,
      previous studies indicate that sibling bullying is associated with depression and
      self-harm behavior. However, the association between sibling bullying and
      suicidal ideation was never previously examined. Attachment to parents is one
      variable that can moderate the association between sibling bullying and
      depression/suicide ideation. To our knowledge, there is no existing study that
      examines the association between sibling bullying and attachment patterns. In
      addition, no previous study has examined the moderating role of attachment on the
      association between sibling bullying and depression or suicidal ideation among
      adolescents. The current study includes 279 Israeli students aged 10-17 (M =
      13.5; SD = 1.98; 164, 58.8% females) who completed self-report questionnaires
      regarding school and sibling bullying, attachment to mother and father,
      depression, and suicidal ideation. The results indicated an association between
      bullying among siblings and school bullying. In addition, children and
      adolescents who were consistently involved in sibling bullying were at greater
      risk for depression and suicide ideation when compared to children and
      adolescents who were not involved in sibling bullying. A secure attachment to
      one's father (but not to one's mother) moderated the association between sibling
      bullying and depression/suicide ideation. It should be noted that when suicide
      ideation was examined above and beyond depression, attachment to one's father did
      not moderate the association between sibling bullying involvement and suicide
      ideation. This finding indicates that depression plays a central role in the
      association between sibling bullying and suicide ideation. These results suggest
      that sibling bullying is a risk factor for depressive symptoms and suicide
      ideation and that secure attachment to one's father may serve as a protective
      role. Future bullying prevention programs should include sibling bullying and
      encourage the increased availability of paternal emotional support. Other
      theoretical and applied implications for prevention of both sibling bullying and
      suicide are discussed.

PMID- 29593582
TI  - Acute Effects of Glucose and Fructose Administration on the Neural Correlates of
      Cognitive Functioning in Healthy Subjects: A Pilot Study.
AB  - The present randomized double-blinded cross-over study aims to extensively study
      the neural correlates underpinning cognitive functions in healthy subjects after
      acute glucose and fructose administration, using an integrative multimodal
      neuroimaging approach. Five minutes after glucose, fructose, or placebo
      administration through a nasogastric tube, 12 participants underwent 3
      complementary neuroimaging techniques: 2 task-based functional magnetic resonance
      imaging (fMRI) sequences to assess working memory (N-back) and response
      inhibition (Go/No-Go) and one resting state fMRI sequence to address the
      cognition-related fronto-parietal network (FPN) and salience network (SN). During
      working memory processing, glucose intake decreased activation in the anterior
      cingulate cortex (ACC) relative to placebo, while fructose decreased activation
      in the ACC and sensory cortex relative to placebo and glucose. During response
      inhibition, glucose and fructose decreased activation in the ACC, insula and
      visual cortex relative to placebo. Resting state fMRI indicated increased global
      connectivity strength of the FPN and the SN during glucose and fructose intake.
      The results demonstrate that glucose and fructose lead to partially different
      partially overlapping changes in regional brain activities that underpin
      cognitive performance in different tasks.

PMID- 29593584
TI  - Utilization of Mental Health Care, Treatment Patterns, and Course of Psychosocial
      Functioning in Northern German Coronary Artery Disease Patients with Depressive
      and/or Anxiety Disorders.
AB  - Background: Comorbid mental disorders in patients with coronary artery disease
      (CAD) are common and associated with adverse somatic outcomes. However, data on
      utilization rates of mental health care and treatment efficiency are scarce and
      inconsistent, which we tried to remedy with the present preliminary study on
      Northern German CAD patients. Method: A total of 514 German CAD patients, as
      diagnosed by cardiac catheterization, were assessed using the Mini International
      Neuropsychiatric Interview and the Global Assessment of Functioning (GAF) scale.
      Results: Global utilization of mental health care since onset of CAD was 21.0%.
      Depressive disorders, younger age, and lower GAF at onset of CAD were associated
      with higher utilization rates, while anxiety disorders and gender were not. Lower
      GAF at onset of CAD, female gender, and psychotherapy was positively associated
      with higher gains in GAF, while younger age and anxiety disorders were negatively
      associated. Conclusion: The majority of CAD patients with comorbid depression
      reported to have received mental health treatment and seemed to have benefited
      from it. However, we found preliminary evidence of insufficiencies in the
      diagnosis and treatment of anxiety disorders in CAD patients. Further studies,
      preferably prospective and with representative samples, are needed to corroborate
      or falsify these findings and explore possible further mediators of health-care
      utilization by CAD patients such as race, ethnicity, and socioeconomic status.

PMID- 29593585
TI  - Functional Magnetic Resonance Spectroscopy: The "New" MRS for Cognitive
      Neuroscience and Psychiatry Research.
AB  - Proton magnetic resonance spectroscopy (1H MRS) is a well-established technique
      for quantifying the brain regional biochemistry in vivo. In most studies,
      however, the 1H MRS is acquired during rest with little to no constraint on
      behavior. Measured metabolite levels, therefore, reflect steady-state
      concentrations whose associations with behavior and cognition are unclear. With
      the recent advances in MR technology-higher-field MR systems, robust acquisition
      techniques and sophisticated quantification methods-1H MRS is now experiencing a
      resurgence. It is sensitive to task-related and pathology-relevant regional
      dynamic changes in neurotransmitters, including the most ubiquitous among them,
      glutamate. Moreover, high temporal resolution approaches allow tracking glutamate
      modulations at a time scale of under a minute during perceptual, motor, and
      cognitive tasks. The observed task-related changes in brain glutamate are
      consistent with new metabolic steady states reflecting the neural output driven
      by shifts in the local excitatory and inhibitory balance on local circuits.
      Unlike blood oxygen level differences-base functional MRI, this form of in vivo
      MRS, also known as functional MRS (1H fMRS), yields a more direct measure of
      behaviorally relevant neural activity and is considerably less sensitive to
      vascular changes. 1H fMRS enables noninvasive investigations of task-related
      glutamate changes that are relevant to normal and impaired cognitive performance,
      and psychiatric disorders. By targeting brain glutamate, this approach taps into
      putative neural correlates of synaptic plasticity. This review provides a concise
      survey of recent technological advancements that lay the foundation for the
      successful use of 1H fMRS in cognitive neuroscience and neuropsychiatry,
      including a review of seminal 1H fMRS studies, and the discussion of biological
      significance of task-related changes in glutamate modulation. We conclude with a
      discussion of the promises, limitations, and outstanding challenges of this new
      tool in the armamentarium of cognitive neuroscience and psychiatry research.

PMID- 29593586
TI  - The Association Between Suicidal Behavior, Attentional Control, and Frontal
      Asymmetry.
AB  - It can be difficult to identify those at risk of suicide because suicidal
      thoughts are often internalized and not shared with others. Yet to prevent
      suicide attempts it is crucial to identify suicidal thoughts and actions at an
      early stage. Past studies have suggested that deficits in attentional control are
      associated with suicide, with the argument that individuals are unable to inhibit
      negative thoughts and direct resources away from negative information. The
      current study aimed to investigate the association of suicidal behavior with
      neurological and behavioral markers, measuring attentional bias and inhibition in
      two Stroop tasks. Fifty-four participants responded to the color of color words
      in a standard Stroop task and the color of positive, negative, and neutral words
      in an emotional Stroop task. Electroencephalographic (EEG) activity was recorded
      from frontal areas during each task and at resting. Participants were separated
      into a low-risk and high-risk group according to their self-reported suicidal
      behavior. Participants in the high-risk group showed slower response times in the
      color Stroop and reduced accuracy to incongruent trials, but faster response
      times in the emotional Stroop task. Response times to the word "suicide" were
      significantly slower for the high-risk group. This indicates an attentional bias
      toward specific negative stimuli and difficulties inhibiting information for
      those with high levels of suicidal behavior. In the emotional Stroop task the
      high-risk group showed reduced activity in leftward frontal areas, suggesting
      limitations in the ability to regulate emotional processing via the left frontal
      regions. The findings support the argument that deficits in attentional control
      are related to suicidal behavior. The research also suggests that under certain
      conditions frontal asymmetry may be associated with suicidal behavior.

PMID- 29593587
TI  - Circulating MicroRNA Expression Levels Associated With Internet Gaming Disorder.
AB  - Background: Addictive use of the Internet and online games is a potential
      psychiatric disorder termed Internet gaming disorder (IGD). Altered microRNA
      (miRNA) expression profiles have been reported in blood and brain tissue of
      patients with certain psychiatric disorders and suggested as biomarkers. However,
      there have been no reports on blood miRNA profiles in IGD. Methods: To discover
      IGD-associated miRNAs, we analyzed the miRNA expression profiles of 51 samples
      (25 IGD and 26 controls) using the TaqMan Low Density miRNA Array. For
      validation, we performed quantitative reverse transcription PCR with 36
      independent samples (20 IGD and 16 controls). Results: Through discovery and
      independent validation, we identified three miRNAs (hsa-miR-200c-3p, hsa-miR-26b
      5p, hsa-miR-652-3p) that were significantly downregulated in the IGD group.
      Individuals with all three miRNA alterations had a much higher risk of IGD than
      those with no alteration [odds ratio (OR) 22, 95% CI 2.29-211.11], and the ORs
      increased dose dependently with number of altered miRNAs. The predicted target
      genes of the three miRNAs were associated with neural pathways. We explored the
      protein expression of the three downstream target genes by western blot and
      confirmed that expression of GABRB2 and DPYSL2 was significantly higher in the
      IGD group. Conclusion: We observed that expressions of hsa-miR-200c-3p, hsa-miR
      26b-5p, and hsa-miR-652-3p were downregulated in the IGD patients. Our results
      will be helpful to understand the pathophysiology of IGD.

PMID- 29593588
TI  - Carbonyl Stress and Microinflammation-Related Molecules as Potential Biomarkers
      in Schizophrenia.
AB  - This literature review primarily aims to summarize our research, comprising both
      cross-sectional and longitudinal studies, and discuss the possibility of using
      microinflammation-related biomarkers as peripheral biomarkers in the diagnosis
      and monitoring of patients with schizophrenia. To date, several studies have been
      conducted on peripheral biomarkers to recognize the potential markers for the
      diagnosis of schizophrenia and to determine the state and effects of therapy in
      patients with schizophrenia. Research has established a correlation between
      carbonyl stress, an environmental factor, and the pathophysiology of
      neuropsychiatric diseases, including schizophrenia. In addition, studies on
      biomarkers related to these stresses have achieved results that are either
      replicable or exhibit consistent increases or decreases in patients with
      schizophrenia. For instance, pentosidine, an advanced glycation end product
      (AGE), is considerably elevated in patients with schizophrenia; however, low
      levels of vitamin B6 [a detoxifier of reactive carbonyl compounds (RCOs)] have
      also been reported in some patients with schizophrenia. Another study on
      peripheral markers of carbonyl stress in patients with schizophrenia revealed a
      correlation of higher levels of glyceraldehyde-derived AGEs with higher
      neurotoxicity and lower levels of soluble receptors capable of diminishing the
      effects of AGEs. Furthermore, studies on evoked microinflammation-related
      biomarkers (e.g., soluble tumor necrosis factor receptor 1) have reported
      relatively consistent results, suggesting the involvement of microinflammation in
      the pathophysiology of schizophrenia. We believe that our cross-sectional and
      longitudinal studies as well as various previous inflammation marker studies that
      could be interpreted from several perspectives, such as mild localized
      encephalitis and microvascular disturbance, highlighted the importance of early
      intervention as prevention and distinguished the possible exclusion of
      inflammations in schizophrenia.

PMID- 29593589
TI  - Comorbid Diagnosis of Psychotic Disorders in Borderline Personality Disorder:
      Prevalence and Influence on Outcome.
AB  - Background: A diagnosis of psychotic disorder is traditionally considered
      incompatible with borderline personality disorder (BPD), even though patients
      sometimes fulfill the diagnostic criteria for both disorders. How often this
      happens is barely known, as is the influence of comorbid psychotic disorders on
      the outcome of BPD. Since studies on isolated auditory verbal hallucinations in
      patients with BPD indicate that these perceptual symptoms have severe
      consequences and are associated with suicidal behavior and hospitalization,
      patients with comorbid psychotic disorders are unlikely to fare better.
      Objective: To examine the point prevalence of psychotic disorders in patients
      with BPD, their association with the outcome of BPD, and their predictive value
      for outcome. Methods: In a cross-sectional design, 84 female outpatients
      diagnosed with BPD were interviewed with the aid of the MINI-International
      Neuropsychiatric Interview to establish the point prevalence of comorbid
      psychotic and other comorbid disorders. After termination of their treatment at a
      specialized outpatient clinic, the type of referral was considered to be a "good"
      outcome when they were referred to their general practitioner or to basic
      psychiatric care for noncomplex patients, and a "poor" outcome when referred to a
      specialized psychiatric department or to a psychiatric district team for patients
      with severe psychiatric disorders. Results: Psychotic disorders were present in
      38% of the patients with BPD. With a prevalence of 20%, psychotic disorder not
      otherwise specified (NOS) was the most common subtype; the least common types
      were schizophrenia (2%), substance-induced psychotic disorder (2%), and brief
      psychotic disorder (1%). Among six types of comorbid disorders, only psychotic
      disorders were associated with a poor outcome; they were also predictors for a
      poor outcome, along with comorbid mood disorders, eating disorders, and
      somatoform disorders, as well as the severity of BPD, and, counterintuitively,
      more years of education. Conclusion: Psychotic disorders, notably of the
      psychotic disorder NOS subtype, are common among patients with BPD, and their
      presence is associated with a poor outcome. This implies that adequate diagnosis
      and treatment of both disorders is warranted in this subgroup with a dual
      diagnosis.

PMID- 29593590
TI  - Plasticity, Variability and Age in Second Language Acquisition and Bilingualism.
AB  - Much of what is known about the outcome of second language acquisition and
      bilingualism can be summarized in terms of inter-individual variability,
      plasticity and age. The present review looks at variability and plasticity with
      respect to their underlying sources, and at age as a modulating factor in
      variability and plasticity. In this context we consider critical period effects
      vs. bilingualism effects, early and late bilingualism, nativelike and non
      nativelike L2 attainment, cognitive aging, individual differences in learning,
      and linguistic dominance in bilingualism. Non-uniformity is an inherent
      characteristic of both early and late bilingualism. This review shows how
      plasticity and age connect with biological and experiential sources of
      variability, and underscores the value of research that reveals and explains
      variability. In these ways the review suggests how plasticity, variability and
      age conspire to frame fundamental research issues in L2 acquisition and
      bilingualism, and provides points of reference for discussion of the present
      Frontiers in Psychology Research Topic.

PMID- 29593591
TI  - Assessing Individual Change Without Knowing the Test Properties: Item
      Bootstrapping.
AB  - Assessing significant change (or reliable change) in a person often involve
      comparing the responses of that person in two administrations of a test or scale.
      Several procedures have been proposed to determine if a difference between two
      observed scores is statistically significant or rather is within the range of
      mere random fluctuations due to measurement error. Application of those
      procedures involve some knowledge of the test properties. But sometimes those
      procedures cannot be employed because the properties are unknown or are not
      trustworthy. In this paper we propose the bootstrap of items procedure to create
      confidence intervals of the individual's scores without using any known
      psychometric properties of the test. Six databases containing the responses of
      several groups to one or more subscales have been analyzed using two methods:
      bootstrap of items and a classical procedure based on confidence intervals to
      estimate the true score. The rates of significant change obtained were very
      similar, suggesting that item bootstrapping is a promising solution when other
      methods cannot be applied.

PMID- 29593593
TI  - Using iMCFA to Perform the CFA, Multilevel CFA, and Maximum Model for Analyzing
      Complex Survey Data.
AB  - To construct CFA, MCFA, and maximum MCFA with LISREL v.8 and below, we provide
      iMCFA (integrated Multilevel Confirmatory Analysis) to examine the potential
      multilevel factorial structure in the complex survey data. Modeling multilevel
      structure for complex survey data is complicated because building a multilevel
      model is not an infallible statistical strategy unless the hypothesized model is
      close to the real data structure. Methodologists have suggested using different
      modeling techniques to investigate potential multilevel structure of survey data.
      Using iMCFA, researchers can visually set the between- and within-level factorial
      structure to fit MCFA, CFA and/or MAX MCFA models for complex survey data. iMCFA
      can then yield between- and within-level variance-covariance matrices, calculate
      intraclass correlations, perform the analyses and generate the outputs for
      respective models. The summary of the analytical outputs from LISREL is gathered
      and tabulated for further model comparison and interpretation. iMCFA also
      provides LISREL syntax of different models for researchers' future use. An
      empirical and a simulated multilevel dataset with complex and simple structures
      in the within or between level was used to illustrate the usability and the
      effectiveness of the iMCFA procedure on analyzing complex survey data. The
      analytic results of iMCFA using Muthen's limited information estimator were
      compared with those of Mplus using Full Information Maximum Likelihood regarding
      the effectiveness of different estimation methods.

PMID- 29593592
TI  - Acute Bouts of Exercising Improved Mood, Rumination and Social Interaction in
      Inpatients With Mental Disorders.
AB  - Background: Studies at the macro level (such as longer-term interventions) showed
      that physical activity impacts positively on cognitive-emotional processes of
      patients with mental disorders. However, research focusing on the immediate
      impact of acute bouts of exercise (micro level) are missing. The aim of the
      present study was therefore to investigate whether and to what extent single
      bouts of moderately intense exercise can influence dimensions of psychological
      functioning in inpatients with mental disorders. Method: 129 inpatients (mean
      age: 38.16 years; 50.4% females) took part and completed a questionnaire both
      immediately before and immediately after exercising. Thirty inpatients completed
      the questionnaires a second time in the same week. The questionnaire covered
      socio-demographic and illness-related information. Further, the questionnaire
      asked about current psychological states such as mood, rumination, social
      interactions, and attention, tiredness, and physical strengths as a proxy of
      physiological states. Results: Psychological states improved from pre- to post
      session. Improvements were observed for mood, social interactions, attention, and
      physical strengths. Likewise, rumination and tiredness decreased. Mood,
      rumination, and tiredness further improved, when patients completed the
      questionnaires the second time in the same week. Conclusion: At micro level,
      single bouts of exercise impacted positively on cognitive-emotional processes
      such as mood, rumination, attention and social interactions, and physiological
      states of tiredness and physical strengths among inpatients with mental
      disorders. In addition, further improvements were observed, if patients
      participated in physical activities a second time.

PMID- 29593594
TI  - Effects of Grammatical Structure of Compound Words on Word Recognition in
      Chinese.
AB  - Two lexical priming experiments were conducted to examine effects of grammatical
      structure of Chinese two-constituent compounds on their recognition. The target
      compound words conformed to two types of grammatical structure: subordinate and
      coordinative compounds. Subordinate compounds follow a structure where the first
      constituent modifies the second constituent (e.g., , meaning snowball); here the
      meaning of the second constituent (head) is modified by the first constituent
      (modifier). On the other hand, in coordinative compounds both constituents
      contribute equally to the word meaning (e.g., , wind and rain, meaning storm
      where the two constituent equally contribute to the word meaning). In Experiment
      1 that was a replication attempt of Liu and McBride-Chang (2010), possible
      priming effects of word structure and semantic relatedness were examined. In
      lexical decision latencies only a semantic priming effect was observed. In
      Experiment 2, compound word structure and individual constituents were primed by
      the prime and target sharing either the first or second constituent. A structure
      priming effect was obtained in lexical decision times for subordinate compounds
      when the prime and target compound shared the same constituent. This suggests
      that a compound word constituent (either the modifier or the head) has to be
      simultaneously active with the structure information in order for the structure
      information to exert an effect on compound word recognition in Chinese. For the
      coordinative compounds the structure priming effect was non-significant. When the
      meaning of the whole word was primed (Experiment 1), no structure effect was
      observable. The pattern of results suggests that effects of structure priming are
      constituent-specific and no general structure priming was observable.

PMID- 29593595
TI  - How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi
      Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased
      Hedonic Valence of Food in Eating Disorders.
AB  - Background: Despite on-going efforts to better understand dysregulated eating,
      the olfactory-gustatory deficits and food preferences in eating disorders (ED),
      and the mechanisms underlying the perception of and responses to food properties
      in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both
      during the course of the illness and compared to healthy populations. It is,
      therefore, necessary to systematically investigate the gustatory perception and
      hedonics of taste in patients with AN and BN. To this end, we will examine
      whether aversions to the taste of high-calorie food is related to the suppression
      of energy intake in restricting-type AN, and whether an increased hedonic valence
      of sweet, caloric-dense foods may be part of the mechanisms triggering binge
      eating episodes in BN. In addition, the role of cognitions influencing these
      mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat
      stimuli will be presented in a sensory two-alternative forced-choice test
      involving signal detection analysis. In study 2, a full-scale taste reactivity
      test will be carried out, including psychophysiological and behavioral measures
      to assess subtle and covert hedonic changes. We will compare the responses of
      currently-ill AN and BN patients to those who have recovered from AN and BN, and
      also to those of healthy normal-weight and underweight individuals without any
      eating disorder pathology. Discussion: If taste response profiles are
      differentially linked to ED types, then future studies should investigate whether
      taste responsiveness represents a useful diagnostic measure in the prevention,
      assessment and treatment of EDs. The expected results on cognitive mechanisms in
      the top-down processes of food hedonics will complement current models and
      contribute to the refinement of interventions to change cognitive aspects of
      taste aversions, to establish functional food preferences and to better manage
      food cravings associated with binge-eating episodes. No trial registration was
      required for this protocol, which was approved by the Swiss ethics committee (CER
      VD, n degrees  2016-02150) and the Ethics Review Panel of the University of
      Luxembourg.

PMID- 29593597
TI  - Comprehension of Generalized Conversational Implicatures by Children With and
      Without Autism Spectrum Disorder.
AB  - This study evaluates the comprehension of generalized conversational implicatures
      (GCI) in children with and without autism spectrum disorder (ASD), using a GCI
      test constructed based on the Levinson model, which distinguishes between three
      types of implicatures: type Q (or scalar: "what is not referred to does not
      occur"); type I ("by default, it is not necessary to say what can be assumed");
      and type M ("if someone is expressing something in a not very simple or marked
      way, it is because s/he is describing a situation that is not very typical,
      frequent, or prototypical"). In addition to the ASD group (n = 22), two
      comparison groups were utilized: a group matched on chronological age with the
      ASD group, but with a higher linguistic age (TCD group, n = 22), and a group
      matched on linguistic age with the ASD group, but with a lower chronological age
      (TLD group, n = 22). In all cases, linguistic age was assessed with the Peabody
      test. The performance of the three groups on the GCI test was compared (overall
      and on each type of implicature), and performance on the three types of
      implicature was compared within each group. The ASD group obtained worse
      performance than the other two groups, both overall and for each implicature
      type, without also obtaining differences in performance on the three implicature
      types. The TCD group obtained better performance than the TLD group on overall
      performance, but not on each implicature type, and both groups obtained lower
      performance on the type M heuristics than on the type I. Based on these results,
      the children with ASD in our study presented limitations in the comprehension of
      the three types of GCI, but it was not possible to obtain evidence for an
      inferential continuum of the three types of GCI. However, in the two typical
      development groups, this evidence was obtained, leading us to propose an
      inferential continuum model based on the different levels of dependence on the
      context of each of the three types of implicatures, with type M implicatures
      being more contextually dependent.

PMID- 29593596
TI  - Neural Dynamics of Autistic Repetitive Behaviors and Fragile X Syndrome: Basal
      Ganglia Movement Gating and mGluR-Modulated Adaptively Timed Learning.
AB  - This article develops the iSTART neural model that proposes how specific
      imbalances in cognitive, emotional, timing, and motor processes that involve
      brain regions like prefrontal cortex, temporal cortex, amygdala, hypothalamus,
      hippocampus, and cerebellum may interact together to cause behavioral symptoms of
      autism. These imbalances include underaroused emotional depression in the
      amygdala/hypothalamus, learning of hyperspecific recognition categories that help
      to cause narrowly focused attention in temporal and prefrontal cortices, and
      breakdowns of adaptively timed motivated attention and motor circuits in the
      hippocampus and cerebellum. The article expands the model's explanatory range by,
      first, explaining recent data about Fragile X syndrome (FXS), mGluR, and trace
      conditioning; and, second, by explaining distinct causes of stereotyped behaviors
      in individuals with autism. Some of these stereotyped behaviors, such as an
      insistence on sameness and circumscribed interests, may result from imbalances in
      the cognitive and emotional circuits that iSTART models. These behaviors may be
      ameliorated by operant conditioning methods. Other stereotyped behaviors, such as
      repetitive motor behaviors, may result from imbalances in how the direct and
      indirect pathways of the basal ganglia open or close movement gates,
      respectively. These repetitive behaviors may be ameliorated by drugs that augment
      D2 dopamine receptor responses or reduce D1 dopamine receptor responses. The
      article also notes the ubiquitous role of gating by basal ganglia loops in
      regulating all the functions that iSTART models.

PMID- 29593598
TI  - How to Detect Insight Moments in Problem Solving Experiments.
AB  - Arguably, it is not possible to study insight moments during problem solving
      without being able to accurately detect when they occur (Bowden and Jung-Beeman,
      2007). Despite over a century of research on the insight moment, there is
      surprisingly little consensus on the best way to measure them in real-time
      experiments. There have also been no attempts to evaluate whether the different
      ways of measuring insight converge. Indeed, if it turns out that the popular
      measures of insight diverge, then this may indicate that researchers who have
      used one method may have been measuring a different phenomenon to those who have
      used another method. We compare the strengths and weaknesses of the two most
      commonly cited ways of measuring insight: The feelings-of-warmth measure adapted
      from Metcalfe and Wiebe (1987), and the self-report measure adapted from Bowden
      and Jung-Beeman (2007). We find little empirical agreement between the two
      measures, and conclude that the self-report measure of Aha! is superior both
      methodologically and theoretically, and provides a better representation of what
      is commonly regarded as insight. We go on to describe and recommend a novel
      visceral measure of insight using a dynamometer as described in Creswell et al.
      (2016).

PMID- 29593599
TI  - Recounting a Common Experience: On the Effectiveness of Instructing Eyewitness
      Pairs.
AB  - Pairs of eyewitnesses with a content-focused interaction style remember
      significantly more about witnessed incidents. We examined whether content-focused
      retrieval strategies can be taught. Seventy-five pairs of witnesses were
      interviewed thrice about an event. The first and third interview were conducted
      individually for all witnesses. The second interview was individual,
      collaborative without instruction, or collaborative with instruction. Pairs in
      the latter condition were instructed to actively listen to and elaborate upon
      each other's contributions. The strategy instruction had no effect on retrieval
      strategies used, nor on the amount or accuracy of reported information. However,
      pairs who spontaneously adopted a content-focused interaction style during the
      collaborative interview remembered significantly more. Thus, our findings show
      that effective retrieval strategies cannot be taught, at least not with the
      current instructions. During the second interview, we observed collaborative
      inhibition and error pruning. When considering the total amount of information
      reported across the first two interviews, however, collaboration had no
      inhibitory effect on correct recall, yet the error pruning benefits remained.
      These findings suggest that investigative interviewers should interview witnesses
      separately first, and then interview pairs of witnesses collaboratively.

PMID- 29593601
TI  - Designing Smart Objects to Support Affording Situations: Exploiting Affordance
      Through an Understanding of Forms of Engagement.
AB  - In this paper I consider how the concept of "affordance" has been adapted from
      the original writings of Gibson and applied to interaction design. I argue that a
      clear understanding of affordance shifts the goal of interaction design from one
      of solely focusing on either the physical object or the capabilities of the
      person, toward an understanding of interactivity. To do this, I develop the
      concept of Forms of Engagement, originally proposed to account for tool use.
      Finally, I extend this concept to interacting with modified tangible user
      interfaces, or "animate objects." These animate objects not only sense how they
      are being used, but also communicate with each other to develop a shared intent,
      and provide prompts and cues to encourage specific actions. In this way, the
      human-object-environment system creates affording situations in pursuit of shared
      intentions and goals. In order to determine when to provide prompts and cues, the
      objects need to have a model of how they ought to be used and what intention they
      are being used to achieve. Consequently, affordances become not only the means by
      which actions are encouraged but also the manner in which intentions are
      identified and agreed.

PMID- 29593600
TI  - Action Prediction Allows Hypothesis Testing via Internal Forward Models at 6
      Months of Age.
AB  - We propose that action prediction provides a cornerstone in a learning process
      known as internal forward models. According to this suggestion infants'
      predictions (looking to the mouth of someone moving a spoon upward) will moments
      later be validated or proven false (spoon was in fact directed toward a bowl),
      information that is directly perceived as the distance between the predicted and
      actual goal. Using an individual difference approach we demonstrate that action
      prediction correlates with the tendency to react with surprise when social
      interactions are not acted out as expected (action evaluation). This association
      is demonstrated across tasks and in a large sample (n = 118) at 6 months of age.
      These results provide the first indication that infants might rely on internal
      forward models to structure their social world. Additional analysis, consistent
      with prior work and assumptions from embodied cognition, demonstrates that the
      latency of infants' action predictions correlate with the infant's own manual
      proficiency.

PMID- 29593602
TI  - Bouba/Kiki in Touch: Associations Between Tactile Perceptual Qualities and
      Japanese Phonemes.
AB  - Several studies have shown cross-modal associations between sounds and vision or
      gustation by asking participants to match pre-defined sound-symbolic words
      (SSWs), such as "bouba" or "kiki," with visual or gustatory materials. Here, we
      conducted an explorative study on cross-modal associations of tactile sensations
      using spontaneous production of Japanese SSWs and semantic ratings. The Japanese
      language was selected, because it has a large number of SSWs that can represent a
      wide range of tactile perceptual spaces with fine resolution, and it shows strong
      associations between sound and touch. In the experiment, we used 120 everyday
      materials to cover basic material categories that could be associated with
      fundamental dimensions of tactile perception. Upon contact with these materials,
      participants expressed their tactile sensations by using Japanese SSWs, and at
      the same time, evaluated the tactile sensations by semantic differential scales
      using adjective pairs. Thanks to the variety of testing materials, we were able
      to demonstrate the existence of systematic associations between sounds and
      tactile fundamental perceptual dimensions in a more detailed and comprehensive
      way than ever done so before. In particular, we found that for vowels, positive
      tactile ratings were associated with the back vowel (/u/), while negative ratings
      were associated with the front vowels (/i/ and /e/). The central vowels (/o/ and
      /a/) were mainly associated with rough, hard, and dry feelings. Consonants were
      categorized based on vocal features and articulation. The category of the voiced
      consonants (e.g., /dz/ and /g/) corresponded to feelings of roughness, while that
      of voiceless consonants (e.g., /ts/, and /s/) corresponded to feelings of
      smoothness. The categories of the bilabial plosive (/p/ and /b/) and voiced
      alveolar nasal (/n/) consonants were mainly related to soft, sticky and wet
      feelings, while that of voiceless alveolar affricate (/ts/) and voiceless velar
      plosive (/k/) consonants were related to hard, slippery and dry feelings.

PMID- 29593603
TI  - Academic Well-Being, Mathematics Performance, and Educational Aspirations in
      Lower Secondary Education: Changes Within a School Year.
AB  - It has been suggested that both performance and academic well-being play a role
      in adolescent students' educational attainment and school dropout. In this study,
      we therefore examined, first, what kinds of academic well-being (i.e., school
      burnout, schoolwork engagement, and mathematics self-concept) and mathematics
      performance profiles can be identified among lower secondary school students
      (Ngrade 7 = 583, Ngrade 9 = 497); second, how stable these profiles are across
      one school year during the seventh and ninth grades; and, third, how students
      with different academic well-being and mathematics performance profiles differ
      with respect to their educational aspirations. By means of latent profile
      analyses, three groups of students in seventh grade: thriving (34%), average
      (51%), and negative academic well-being (15%) and four groups of students in
      ninth grade: thriving (25%), average (50%), negative academic well-being (18%),
      and low-performing (7%) with distinct well-being and mathematics performance
      profiles were identified. Configural frequency analyses revealed that the
      profiles were relatively stable across one school year; 60% of the students
      displayed identical profiles over time. The thriving students reported the
      highest educational aspirations compared to the other groups. In addition, the
      low-performing students in the ninth grade had the lowest educational aspirations
      just before the transition to upper secondary school. Practical implications as
      well as directions for future research are discussed.

PMID- 29593605
TI  - EEG Correlates of the Flow State: A Combination of Increased Frontal Theta and
      Moderate Frontocentral Alpha Rhythm in the Mental Arithmetic Task.
AB  - Flow experience is a subjective state experienced during holistic involvement in
      a certain activity, which has been reported to function as a factor promoting
      motivation, skill development, and better performance in the activity. To verify
      the positive effects of flow and develop a method to utilize it, the
      establishment of a reliable measurement of the flow state is essential. The
      present study utilized an electroencephalogram (EEG) during an experimentally
      evoked flow state and examined the possibility of objective measurement of
      immediate flow. A total of 16 participants (10 males, 6 females) participated in
      the experiment that employed a mental arithmetic task developed in a previous
      study. Post-trial self-report of the flow state and EEG during task execution
      were measured and compared among three conditions (Boredom, Flow, and Overload)
      that had different levels of task difficulty. Furthermore, the correlations
      between subjective flow items and EEG activity were examined. As expected, the
      ratings on the subjective evaluation items representing the flow state were the
      highest in the Flow condition. Regarding the EEG data, theta activities in the
      frontal areas were higher in the Flow and the Overload conditions than in the
      Boredom condition, and alpha activity in the frontal areas and the right central
      area gradually increased depending on the task difficulty. These EEG activities
      correlated with self-reported flow experience, especially items related to the
      concentration on the task and task difficulty. From the results, the flow state
      was characterized by increased theta activities in the frontal areas and moderate
      alpha activities in the frontal and central areas. The former may be related to a
      high level of cognitive control and immersion in task, and the latter suggests
      that the load on the working memory was not excessive. The findings of this study
      suggest the possibility of distinguishing the flow state from other states using
      multiple EEG activities and indicate the need for other physiological indicators
      corresponding to the other aspects of flow experience.

PMID- 29593604
TI  - Moderators Influencing the Effectiveness of a Behavioral Teacher Program.
AB  - Objective: This study assessed which moderators influenced the effectiveness of a
      low-intensive behavioral teacher program for children with symptoms of Attention
      Deficit/Hyperactivity Disorder (ADHD). Methods: Primary school children (N = 114)
      with ADHD symptoms in the classroom were randomly assigned to the intervention
      program (n = 58; 91% male) or control group (n = 56; 77% male). Multilevel
      regression analyses assessed differential treatment gains of the intervention
      program in terms of ADHD symptoms and social skills. Moderators included
      demographic characteristics (gender, age, parental educational level), severity
      and comorbidity of problem behavior (ADHD symptoms, conduct and internalizing
      problems), social functioning, and classroom variables (teaching experience,
      class size). Results: Results revealed larger program effects for older children
      and children from highly educated families and smaller beneficial effects for
      children with comorbid conduct or anxiety problems. Conclusion: The intervention
      program seems more beneficial for highly educated families and children without
      comorbid problem behavior, but more intensive treatments appear necessary for
      children facing additional challenges. ClinicalTrials.gov registration number:
      NCT02518711.

PMID- 29593606
TI  - The Efficacy and Development of Students' Problem-Solving Strategies During
      Compulsory Schooling: Logfile Analyses.
AB  - The purpose of this study was to examine the role of exploration strategies
      students used in the first phase of problem solving. The sample for the study was
      drawn from 3rd- to 12th-grade students (aged 9-18) in Hungarian schools (n =
      4,371). Problems designed in the MicroDYN approach with different levels of
      complexity were administered to the students via the eDia online platform.
      Logfile analyses were performed to ascertain the impact of strategy use on the
      efficacy of problem solving. Students' exploration behavior was coded and
      clustered through Latent Class Analyses. Several theoretically effective
      strategies were identified, including the vary-one-thing-at-a-time (VOTAT)
      strategy and its sub-strategies. The results of the analyses indicate that the
      use of a theoretically effective strategy, which extract all information required
      to solve the problem, did not always lead to high performance. Conscious VOTAT
      strategy users proved to be the best problem solvers followed by non-conscious
      VOTAT strategy users and non-VOTAT strategy users. In the primary school sub
      sample, six qualitatively different strategy class profiles were distinguished.
      The results shed new light on and provide a new interpretation of previous
      analyses of the processes involved in complex problem solving. They also
      highlight the importance of explicit enhancement of problem-solving skills and
      problem-solving strategies as a tool for knowledge acquisition in new contexts
      during and beyond school lessons.

PMID- 29593607
TI  - Observation of Point-Light-Walker Locomotion Induces Motor Resonance When
      Explicitly Represented; An EEG Source Analysis Study.
AB  - Understanding human motion, to infer the goal of others' actions, is thought to
      involve the observer's motor repertoire. One prominent class of actions, the
      human locomotion, has been object of several studies, all focused on manipulating
      the shape of degraded human figures like point-light walker (PLW) stimuli,
      represented as walking on the spot. Nevertheless, since the main goal of the
      locomotor function is to displace the whole body from one position to the other,
      these stimuli might not fully represent a goal-directed action and thus might not
      be able to induce the same motor resonance mechanism expected when observing a
      natural locomotion. To explore this hypothesis, we recorded the event-related
      potentials (ERP) of canonical/scrambled and translating/centered PLWs decoding.
      We individuated a novel ERP component (N2c) over central electrodes, around 435
      ms after stimulus onset, for translating compared to centered PLW, only when the
      canonical shape was preserved. Consistently with our hypothesis, sources analysis
      associated this component to the activation of trunk and lower legs primary
      sensory-motor and supplementary motor areas. These results confirm the role of
      own motor repertoire in processing human action and suggest that ERP can detect
      the associated motor resonance only when the human figure is explicitly involved
      in performing a meaningful action.

PMID- 29593608
TI  - No Evidence for Phase-Specific Effects of 40 Hz HD-tACS on Multiple Object
      Tracking.
AB  - Phase synchronization drives connectivity between neural oscillators, providing a
      flexible mechanism through which information can be effectively and selectively
      routed between task-relevant cortical areas. The ability to keep track of objects
      moving between the left and right visual hemifields, for example, requires the
      integration of information between the two cerebral hemispheres. Both animal and
      human studies have suggested that coherent (or phase-locked) gamma oscillations
      (30-80 Hz) might underlie this ability. While most human evidence has been
      strictly correlational, high-density transcranial alternating current stimulation
      (HD-tACS) has been used to manipulate ongoing interhemispheric gamma phase
      relationships. Previous research showed that 40 Hz tACS delivered bilaterally
      over human motion complex could bias the perception of a bistable ambiguous
      motion stimulus (Helfrich et al., 2014). Specifically, this work showed that in
      phase (0 degrees  offset) stimulation boosted endogenous interhemispheric gamma
      coherence and biased perception toward the horizontal (whereby visual tokens
      moved between visual hemifields-requiring interhemispheric integration). By
      contrast, anti-phase (180 degrees  offset) stimulation decreased interhemispheric
      gamma coherence and biased perception toward the vertical (whereby tokens moved
      within separate visual hemifields). Here we devised a multiple object tracking
      arena comprised of four quadrants whereby discrete objects moved either entirely
      within the left and right visual hemifields, or could cross freely between visual
      hemifields, thus requiring interhemispheric integration. Using the same HD-tACS
      montages as Helfrich et al. (2014), we found no phase-specific effect of 40 Hz
      stimulation on overall tracking performance. While tracking performance was
      generally lower during between-hemifield trials (presumably reflecting a cost of
      integration), this difference was unchanged by in- vs. anti-phase stimulation.
      Our null results could be due to a failure to reliably modulate coherence in our
      study, or that our task does not rely as heavily on this network of coherent
      gamma oscillations as other visual integration paradigms.

PMID- 29593609
TI  - Early-Life Stressors, Personality Development, and Fast Life Strategies: An
      Evolutionary Perspective on Malevolent Personality Features.
AB  - Life history theory posits that behavioral adaptation to various environmental
      (ecological and/or social) conditions encountered during childhood is regulated
      by a wide variety of different traits resulting in various behavioral strategies.
      Unpredictable and harsh conditions tend to produce fast life history strategies,
      characterized by early maturation, a higher number of sexual partners to whom one
      is less attached, and less parenting of offspring. Unpredictability and harshness
      not only affects dispositional social and emotional functioning, but may also
      promote the development of personality traits linked to higher rates of
      instability in social relationships or more self-interested behavior. Similarly,
      detrimental childhood experiences, such as poor parental care or high parent
      child conflict, affect personality development and may create a more distrustful,
      malicious interpersonal style. The aim of this brief review is to survey and
      summarize findings on the impact of negative early-life experiences on the
      development of personality and fast life history strategies. By demonstrating
      that there are parallels in adaptations to adversity in these two domains, we
      hope to lend weight to current and future attempts to provide a comprehensive
      insight of personality traits and functions at the ultimate and proximate levels.

PMID- 29593610
TI  - Exploring an Age Difference in Preschool Children's Competitiveness Following a
      Competition.
AB  - Literature suggests that resource acquisition compels competition in young
      children. However, little is still known about the development of preschool
      children's competitiveness. In this preliminary study, 166 children (aged 2-4 and
      5-6 years) engaged in a dyadic competition which resulted in a winning and a
      losing group (in a control/non-competition group, participants engaged in a
      similar task which did not lead to winning/losing outcome), and then
      experimenters tracked their decisions to compete again with a rival (i.e., an
      individual they interacted in the previous competition task) and a non-rival
      competitor (i.e., an anonymous classmate they did not interact in the previous
      competition task) for a reward, respectively. As expected, results showed an age
      related decreasing trend in the percentage of choices to compete with a
      competitor. However, this age difference was only significant in the control
      group when participants played with the partner with whom they interacted in the
      previous game and in the losing group when participants competed with a non-rival
      competitor. This study contributes to our knowledge of how competitiveness
      develop in preschool childhood, and calls for further research on the roles of
      motivation and cognitive control in children's competitiveness.

PMID- 29593611
TI  - Evaluation and Adaption of the Trier Inventory for Chronic Stress (TICS) for
      Assessment in Competitive Sports.
AB  - The demands of a career in competitive sports can lead to chronic stress
      perception among athletes if there is a non-conformity of requirements and
      available coping resources. The Trier Inventory for Chronic Stress (TICS) (Schulz
      et al., 2004) is said to be thoroughly validated. Nevertheless, it has not yet
      been subjected to a confirmatory factor analysis. The present study aims (1) to
      evaluate the factorial validity of the TICS within the context of competitive
      sports and (2) to adapt a short version (TICS-36). The total sample consisted of
      564 athletes (age in years: M = 19.1, SD = 3.70). The factor structure of the
      original TICS did not adequately fit the present data, whereas the short version
      presented a satisfactory fit. The results indicate that the TICS-36 is an
      economical instrument for gathering interpretable information about chronic
      stress. For assessment in competitive sports with TICS-36, we generated overall
      and gender-specific norm values.

PMID- 29593612
TI  - Efficiency in Rule- vs. Plan-Based Movements Is Modulated by Action-Mode.
AB  - The rule/plan motor cognition (RPMC) paradigm elicits visually indistinguishable
      motor outputs, resulting from either plan- or rule-based action-selection, using
      a combination of essentially interchangeable stimuli. Previous implementations of
      the RPMC paradigm have used pantomimed movements to compare plan- vs. rule-based
      action-selection. In the present work we attempt to determine the
      generalizability of previous RPMC findings to real object interaction by use of a
      grasp-to-rotate task. In the plan task, participants had to use prospective
      planning to achieve a comfortable post-handle rotation hand posture. The rule
      task used implementation intentions (if-then rules) leading to the same
      comfortable end-state. In Experiment A, we compare RPMC performance of 16 healthy
      participants in pantomime and real object conditions of the experiment, within
      subjects. Higher processing efficiency of rule- vs. plan-based action-selection
      was supported by diffusion model analysis. Results show a significant response
      time increase in the pantomime condition compared to the real object condition
      and a greater response-time advantage of rule-based vs. plan-based actions in the
      pantomime compared to the real object condition. In Experiment B, 24 healthy
      participants performed the real object RPMC task in a task switching vs. a
      blocked condition. Results indicate that plan-based action-selection leads to
      longer response-times and less efficient information processing than rule-based
      action-selection in line with previous RPMC findings derived from the pantomime
      action-mode. Particularly in the task switching mode, responses were faster in
      the rule compared to the plan task suggesting a modulating influence of cognitive
      load. Overall, results suggest an advantage of rule-based action-selection over
      plan-based action-selection; whereby differential mechanisms appear to be
      involved depending on the action-mode. We propose that cognitive load is a factor
      that modulates the advantageous effect of implementation intentions in motor
      cognition on different levels as illustrated by the varying speed advantages and
      the variation in diffusion parameters per action-mode or condition, respectively.

PMID- 29593613
TI  - Ubiquitous Working: Do Work Versus Non-work Environments Affect Decision-Making
      and Concentration?
AB  - New communication technologies and mobile devices have enabled knowledge workers
      to work independently of location and in more than one fixed environment
      (ubiquitous working). Previous research shows that physical environments can
      influence cognition and work performance. We manipulated environment (i.e., a
      virtual office as a typical work environment compared to a virtual garden as a
      non-work environment) and time pressure (i.e., inducing time pressure vs. no time
      pressure) in order to investigate whether the environment influences decision
      making and concentration. N = 109 students participated in this laboratory
      experiment. We posited (a) that a work environment would activate a work-related
      schema which in turn would enhance concentration performance and make decisions
      more risky compared to non-work environments and (b) that the environmental
      effect is more pronounced if time pressure is present compared to conditions
      where no time pressure is present. We found modest hypothesis-confirming main
      effects of environment on decision-making and concentration but no interaction
      effect with time pressure. As we used an innovative methodology that entails
      several limitations, future research is needed to give insights into the process
      and to investigate whether results hold true for all types of work settings, work
      demands, or work activities.

PMID- 29593614
TI  - Effects of Single Compared to Dual Task Practice on Learning a Dynamic Balance
      Task in Young Adults.
AB  - Background: In everyday life, people engage in situations involving the
      concurrent processing of motor (balance) and cognitive tasks (i.e., "dual task
      situations") that result in performance declines in at least one of the given
      tasks. The concurrent practice of both the motor and cognitive task may
      counteract these performance decrements. The purpose of this study was to examine
      the effects of single task (ST) compared to dual task (DT) practice on learning a
      dynamic balance task. Methods: Forty-eight young adults were randomly assigned to
      either a ST (i.e., motor or cognitive task training only) or a DT (i.e., motor
      cognitive training) practice condition. The motor task required participants to
      stand on a platform and keeping the platform as close to horizontal as possible.
      In the cognitive task, participants were asked to recite serial subtractions of
      three. For 2 days, participants of the ST groups practiced the motor or cognitive
      task only, while the participants of the DT group concurrently performed both.
      Root-mean-square error (RMSE) for the motor and total number of correct
      calculations for the cognitive task were computed. Results: During practice, all
      groups improved their respective balance and/or cognitive task performance. With
      regard to the assessment of learning on day 3, we found significantly smaller
      RMSE values for the ST motor (d = 1.31) and the DT motor-cognitive (d = 0.76)
      practice group compared to the ST cognitive practice group but not between the ST
      motor and the DT motor-cognitive practice group under DT test condition. Further,
      we detected significantly larger total numbers of correct calculations under DT
      test condition for the ST cognitive (d = 2.19) and the DT motor-cognitive (d =
      1.55) practice group compared to the ST motor practice group but not between the
      ST cognitive and the DT motor-cognitive practice group. Conclusion: We conclude
      that ST practice resulted in an effective modulation of the trained domain (i.e.,
      motor or cognitive) while only DT practice resulted in an effective modulation of
      both domains (i.e., motor and cognitive). Thus, particularly DT practice frees up
      central resources that were used for an effective modulation of motor and
      cognitive processing mechanisms.

PMID- 29593615
TI  - Who Cares for Those Who Take Care? Risks and Resources of Work in Care Homes.
AB  - Over the years - due to the aging population, the process of corporatisation and
      a demand for a higher quality of services - professionals who work in Care Homes
      have been exposed to an increasing risk of physical and emotional malaise because
      of the number of challenges they've been asked to manage. Given these factors,
      there is a growing interest in the study and understanding of professions in
      geriatric care settings. In the literature there is a prevalence of quantitative
      studies offering an overview in terms of indicators - at the individual or group
      or organizational level - concerning the potential development of situations of
      professional malaise. Conversely, there is a lack of qualitative studies
      exploring the risk and protection factors. For this reason, in this study we
      decided to use a qualitative approach to explore "more up close" this kind of
      organizational context and to keep together the different levels in systemic
      terms in order to identify - according to professionals' perceptions - resource
      factors (in order to leverage these aspects) and fatigue factors (to identify
      them and treat them). Three Italian Care Homes were involved and the interview's
      sample was composed of 45 professionals - 15 nurses, 30 total Patient Care
      Assistants (PCAs) and Auxiliary Care Assistants (ACAs), of these, 17 males and 28
      females, with an average age of 43 years (SD = 0.78) - selected using a sampling
      of maximum variability. From the analysis of the materials there seem to be four
      profiles of the professionals involved. Implications to ensure a functional human
      resource management are discussed for the purpose of promote the well-being of
      the various professionals, and, as a result, an increasing quality of service.

PMID- 29593616
TI  - Factor Structure of the Chinese Version of the Parent Adult-Child Relationship
      Questionnaire.
AB  - The Parent Adult-Child Relationship Questionnaire (PACQ) included two identical
      versions of the 13-item scale, which were administered to each subject, one which
      referred to "relationship with mother" and the other to "relationship with
      father." The PACQ, originally in English, is a self-report measure of the filial
      relationship. The present study aimed to develop a Chinese version of the PACQ
      and use it to explore Chinese parent adult-child relationships. A total of 454
      Chinese adult-children completed the Chinese version of the PACQ. The structure
      of the questionnaire was analyzed using exploratory factor analysis (EFA) and
      confirmatory factor analysis (CFA). We found that the Cronbach's alpha was 0.66
      0.88 for fathers and 0.76-0.91 for mothers, which demonstrates high internal
      consistency reliabilities of the Chinese version of the PACQ. The Chinese version
      of the PACQ for father had similar constructs similar to with those of the
      original English version. However, a new factor for mothers, "attachment," was
      derived from the original English version. The results suggested that the Chinese
      version of PACQ is a valid and reliable measure of relationship quality between
      Chinese adult-children and their parents.

PMID- 29593617
TI  - The Role of Difficulty in Identifying and Describing Feelings in Non-Suicidal
      Self-Injury Behavior (NSSI): Associations With Perceived Attachment Quality,
      Stressful Life Events, and Suicidal Ideation.
AB  - Objective: Core alexithymic features, such as the difficulty in identifying and
      describing feelings, are associated with poor attachment styles and emotional
      trauma, which influence the capacity to regulate affect. Additionally, emotional
      regulation has been found to be the most commonly identified function associated
      with non-suicidal self-injury behavior (NSSI) in adolescents as they attempt to
      modulate strong emotions. However, few studies have examined the link between
      difficulty in identifying and describing feelings (core components of
      alexithymia), NSSI behaviors, quality of attachment, life stressors and suicidal
      ideation in healthy early adolescents. Consequently, this study aims to
      investigate these constructs and the relationship among them in a large non
      clinical sample of adolescents. Methods: Seven hundred and nine middle school
      students (50.4% males), aged 10-15 years (M = 12.6; SD = 1.06) were involved in
      this study. In order to investigate the variables considered in the study, the
      following measures were administered: the Deliberate Self-Harm Inventory
      exploring non-suicidal self-injurious behaviors; the Alexithymia Questionnaire
      for Children examining difficulty in identifying and describing feelings; the
      Inventory of Parent and Peer Attachment assessing the quality of parental and
      peer attachment; the Life Stressor Checklist-Revised outlining
      stressful/traumatic events and the Children's Depression Inventory evaluating
      suicidal ideation. Results: We found significantly positive relationships among
      difficulty in identifying and describing feelings, NSSI behaviors, stressful
      events, and suicidal ideation. Data indicated a significant negative association
      of difficulty in identifying and describing feelings with quality of attachment
      to parents and peers. Further findings highlighted that difficulty in identifying
      and describing feelings significantly mediated the effect of quality of
      attachment (parent and peer) on NSSI and suicidal ideation. Conclusion: The
      ability to identify and describing feelings is important to managing emotional
      expression and understanding the feelings of others, both crucial in attaining
      successful interpersonal relationships. Our data revealed that, while controlling
      for stressful life events, low levels of attachment may increase adolescents'
      difficulty in identifying and describing their own feelings, which in turn may
      increase the risk of both NSSI and suicidal ideation.

PMID- 29593618
TI  - Phonological Awareness and Rapid Automatized Naming Are Independent Phonological
      Competencies With Specific Impacts on Word Reading and Spelling: An Intervention
      Study.
AB  - Phonological awareness (PA) and rapid automatized naming (RAN) have been shown to
      be powerful predictors of reading achievement across many languages. However,
      literature remains unclear: (a) whether RAN is independent of PA, (b) about the
      specific influences of PA and RAN on reading and spelling, and (c) about the
      efficacy of a RAN intervention. This study aims to address these issues by means
      of an intervention design. Precisely, the objectives are (a) to determine whether
      training one competence involves or not an effect on the other, (b) to examine
      whether each intervention based on oral abilities (PA vs. RAN) could improve word
      reading and word spelling performances, and (c) to assess the efficacy of a RAN
      objects' intervention. Thirty-six French-speaking second graders, from two
      Belgian elementary schools, were divided into two groups, and received either a
      PA- or a RAN-objects' intervention. Twenty-five-minute lessons took place at
      school twice a week over a period of 2 months. Both groups were compared on
      multiple experimental measures (PA, RAN, word reading, and word spelling), before
      and immediately after the intervention, and 6 months later. Results showed
      specific efficacy of the two interventions, with participants trained in one
      ability outperforming those from the other group on this specific ability at post
      test. Moreover, the PA intervention revealed transfer effects on the sub-lexical
      processes of spelling, while the RAN intervention enhanced word reading speed.
      Finally, the results demonstrated the efficacy of a RAN-objects' intervention for
      the first time. These findings provide a new piece of evidence showing the
      independence of PA and RAN, each process influencing the acquisition of literacy
      skills in a different way. The efficacy and the specific transfer effects of both
      interventions open up new perspectives for prevention and targeted remediation of
      reading disabilities.

PMID- 29593619
TI  - Psychological Impact of Stalking on Male and Female Health Care Professional
      Victims of Stalking and Domestic Violence.
AB  - The aim of this work was to investigate stalking experiences in a sample of
      Health Care Professionals, or HCPs, who experienced domestic violence in their
      previous relationships with an intimate romantic or non-romantic who had become
      their stalkers. A comparison between males and females was made to highlight the
      differences among the genders. The findings showed that, for the most part, the
      victims experienced stalking by a stalker that was not of the same gender.
      Moreover, the nature of the relationship was romantic, for the most part, for
      both female and male subjects, suggesting that the principal motivation of
      stalking is the disruption of an intimate relationship. Regarding domestic
      violence, females described the phenomenon from a different perspective,
      indicating verbal, physical, and sexual abuse, while males indicated only verbal
      abuse. Females tended to amplify, more than the males, depression, and state and
      trait anxiety. Even if all symptoms were expressed in both females and males, the
      males exhibited a lack of confidence in their bodies, and the emotional literacy
      made the expression of distress more difficult. At the same time, the expression
      of anxiety presented in the women permitted them to become progressively less
      victimized over time; depression and anxiety allow the recognition of these
      symptoms as signs of distress and to intervene to reduce them.

PMID- 29593620
TI  - Planning Abilities in Bilingual and Monolingual Children: Role of Verbal
      Mediation.
AB  - We examined the role of verbal mediation in planning performance of English
      Spanish-speaking bilingual children and monolingual English-speaking children,
      between the ages of 9 and 12 years. To measure planning, children were
      administered the Tower of London (ToL) task. In a dual-task paradigm, children
      completed ToL problems under three conditions: with no secondary task (baseline),
      with articulatory suppression, and with non-verbal motor suppression. Analyses
      revealed generally shorter planning times for bilinguals than monolinguals but
      both groups performed similarly on number of moves and execution times.
      Additionally, bilingual children were more efficient at planning throughout the
      duration of the task while monolingual children showed significant gains with
      more practice. Children's planning times under articulatory suppression were
      significantly shorter than under motor suppression as well as the baseline
      condition, and there was no difference in planning times between monolingual and
      bilingual children during articulatory suppression. These results demonstrate
      that bilingualism influences performance on a complex EF measure like planning,
      and that these effects are not related to verbal mediation.

PMID- 29593621
TI  - Using Anchoring Vignettes to Adjust Self-Reported Personality: A Comparison
      Between Countries.
AB  - Data from self-report tools cannot be readily compared between cultures due to
      culturally specific ways of using a response scale. As such, anchoring vignettes
      have been proposed as a suitable methodology for correcting against this
      difference. We developed anchoring vignettes for the Big Five Inventory-44 (BFI
      44) to supplement its Likert-type response options. Based on two samples (Rwanda:
      n = 423; Philippines: n = 143), we evaluated the psychometric properties of the
      measure both before and after applying the anchoring vignette adjustment. Results
      show that adjusted scores had better measurement properties, including improved
      reliability and a more orthogonal correlational structure, relative to scores
      based on the original Likert scale. Correlations of the Big Five Personality
      Factors with life satisfaction were essentially unchanged after the vignette
      adjustment while correlations with counterproductive were noticeably lower.
      Overall, these changed findings suggest that the use of anchoring vignette
      methodology improves the cross-cultural comparability of self-reported
      personality, a finding of potential interest to the field of global workforce
      research and development as well as educational policymakers.

PMID- 29593622
TI  - Measuring Responsibility and Cooperation in Learning Teams in the University
      Setting: Validation of a Questionnaire.
AB  - Cooperative learning are being used increasingly in the university classroom, in
      order to promote teamwork among students, improve performance and develop
      interpersonal competences. Responsibility and cooperation are two fundamental
      pillars of cooperative learning. Team members' responsibility is a necessary
      condition for the team's success in the assigned tasks. Students must be aware
      that they depend on each other and should make their maximum effort. On the other
      hand, in efficient groups, the members cooperate and pool their efforts to
      achieve the proposed goals. In this research, we propose to create a
      Questionnaire of Group Responsibility and Cooperation in Learning Teams (CRCG).
      Participants in this work were 375 students from the Faculty of Teacher Training
      of the University of Extremadura (Spain). The CRCG has very acceptable
      psychometric characteristics, good internal consistency, and temporal
      reliability. Moreover, structural equation analysis allowed us to verify that the
      latent variables in the two factors found are well defined and, therefore, their
      assessment is adequate. Besides, we found high significant correlations between
      the Learning Team Potency Questionnaire (CPEA) and the total score and the
      factors of the CRCG. This tool will evaluate cooperative skills and offer faculty
      information in order to prepare students for teamwork and conflict resolution.

PMID- 29593623
TI  - The Educational Situation Quality Model: Recent Advances.
AB  - The purpose of this work was to present an educational model developed in recent
      years entitled the "The Educational Situation Quality Model" (MOCSE, acronym in
      Spanish). MOCSE can be defined as an instructional model that simultaneously
      considers the teaching-learning process, where motivation plays a central role.
      It explains the functioning of an educational setting by organizing and relating
      the most important variables which, according to the literature, contribute to
      student learning. Besides being a conceptual framework, this model also provides
      a methodological procedure to guide research and to promote reflection in the
      classroom. It allows teachers to implement effective research-action programs to
      improve teacher-students satisfaction and learning outcomes in the classroom
      context. This work explains the model's characteristics and functioning, recent
      advances, and how teachers can use it in an educational setting with a specific
      subject. This proposal integrates approaches from several relevant psycho
      educational theories and introduces a new perspective into the existing
      literature that will allow researchers to make progress in studying educational
      setting functioning. The initial MOCSE configuration has been refined over time
      in accordance with the empirical results obtained from previous research, carried
      out within the MOCSE framework and with the subsequent reflections that derived
      from these results. Finally, the contribution of the model to improve learning
      outcomes and satisfaction, and its applicability in the classroom, are also
      discussed.

PMID- 29593624
TI  - Intraindividual Variability in Executive Function Performance in Healthy Adults:
      Cross-Sectional Analysis of the NAB Executive Functions Module.
AB  - The current study was aimed at investigating across-tasks intraindividual
      variability, also termed dispersion, in EF performance. The German adaptation of
      the Neuropsychological Assessment Battery (NAB) was used as a measure of EFs.
      Data of 444 participants aged 18-99 from six NAB Executive Functions Module
      subtests (i.e., Planning, Mazes, Letter Fluency, Judgment, Categories, and Word
      Generation) along with the NAB Total Index score as a measure of overall
      cognitive ability were analyzed. Maximum discrepancy (MD) was applied as a
      measure of dispersion. MD values ranged from 0.47 to 5.20 indicating substantial
      across-tasks dispersion in EF performance. Furthermore, dispersion moderately
      decreased with advancing age. Taking overall cognitive ability into account
      revealed that dispersion might be lower at older ages; especially, when
      associated with low overall ability levels. The dedifferentiation hypothesis
      offers a plausible explanation for these findings. That is, the cognitive
      profiles of older people might be less heterogenous than that of younger people,
      which may be due to age-related central nervous system constraints.

PMID- 29593625
TI  - The Potential and Challenges of Digital Well-Being Interventions: Positive
      Technology Research and Design in Light of the Bitter-Sweet Ambivalence of
      Change.
AB  - Along with the dissemination of technical assistance in nearly every part of
      life, there has been growing interest in the potential of technology to support
      well-being and human flourishing. "Positive technology" thereby takes the
      responsible role of a "digital coach," supporting people in achieving personal
      goals and behavior change. The design of such technology requires knowledge of
      different disciplines such as psychology, design and human-computer interaction.
      However, possible synergies are not yet used to full effect, and it needs common
      frameworks to support a more deliberate design of the "therapeutic interaction"
      mediated through technology. For positive technology design, positive psychology,
      and resource oriented approaches appear as particularly promising starting point.
      Besides a general fit of the basic theoretical conceptions of human change, many
      elements of established interventions could possibly be transferred to technology
      design. However, besides the power of focusing on the positive, another
      psychological aspect to consider are the bitter components inherent to change,
      such as the confrontation with a negative status quo, threat of self-esteem, and
      the effort required. The present research discusses the general potential and
      challenges within positive technology design from an interdisciplinary
      perspective with theoretical and practical contributions. Based on the bitter
      sweet ambivalence of change as present in many psychological approaches of
      motivation and behavior change, the bitter-sweet continuum serves as a proxy for
      the mixed emotions and cognitions related to change. An empirical investigation
      of those factors among 177 users of self-improvement technologies provides
      initial support for the usefulness of the bitter-sweet perspective in
      understanding change dynamics. In a next step, the bitter-sweet concept is
      transformed into different design strategies to support positive change. The
      present article aims to deepen the discussion about the responsible role of
      technology as a well-being enhancement tool and to provide a fruitful frame for
      different disciplines involved in positive technology. Two aspects are
      highlighted: First, investigating well-being technology as a form of "therapeutic
      interaction," focusing on the need for sensible design solutions in the emerging
      dialogue between technology and user. Second, a stronger consideration of the
      bitter-sweet ambivalence of change, utilizing (positive) psychology interventions
      to full effect.

PMID- 29593627
TI  - The Bright, the Dark, and the Blue Face of Narcissism: The Spectrum of Narcissism
      in Its Relations to the Metatraits of Personality, Self-Esteem, and the
      Nomological Network of Shyness, Loneliness, and Empathy.
AB  - Grandiose and vulnerable narcissism seem to be uncorrelated in empirical studies,
      yet they share at least some theoretical similarities. In the current study, we
      examine the relation between grandiose (conceptualized as admiration and rivalry)
      and vulnerable narcissism in the context of the Big Five personality traits and
      metatraits, self-esteem, and their nomological network. To this end, participants
      (N = 314) filled in a set of self-report measures via an online survey. Rivalry
      was positively linked with both admiration and vulnerable narcissism. We
      replicated the relations of admiration and rivalry with personality traits and
      metatraits-as well as extended existing knowledge by providing support for the
      theory that vulnerable narcissism is simultaneously negatively related to the
      Stability and Plasticity. Higher scores on vulnerable narcissism and rivalry
      predicted having fragile self-esteem, whereas high scores on admiration predicted
      having optimal self-esteem. The assumed relations with the nomological network
      were confirmed, i.e., vulnerable narcissism and admiration demonstrated a
      contradictory pattern of relation to shyness and loneliness, whilst rivalry
      predicted low empathy. Our results suggest that the rivalry is between vulnerable
      narcissism and admiration, which supports its localization in the self-importance
      dimension of the narcissism spectrum model. It was concluded that whereas
      admiration and rivalry represent the bright and dark face of narcissism,
      vulnerable narcissism represents its blue face.

PMID- 29593626
TI  - Negative Transfer Effects on L2 Word Order Processing.
AB  - Does first language (L1) word order affect the processing of non-canonical but
      grammatical syntactic structures in second language (L2) comprehension? In the
      present study, we test whether L1-Spanish speakers of L2-Basque process subject
      verb-object (SVO) and object-verb-subject (OVS) non-canonical word order
      sentences of Basque in the same way as Basque native speakers. Crucially, while
      OVS orders are non-canonical in both Spanish and Basque, SVO is non-canonical in
      Basque but is the canonical word order in Spanish. Our electrophysiological
      results showed that the characteristics of L1 affect the processing of the L2
      even at highly proficient and early-acquired bilingual populations. Specifically,
      in the non-native group, we observed a left anterior negativity-like component
      when comparing S and O at sentence initial position and a P600 when comparing
      those elements at sentence final position. Those results are similar of those
      reported by Casado et al. (2005) for native speakers of Spanish indicating that
      L2-Basque speakers rely in their L1-Spanish when processing SVO-OVS word order
      sentences. Our results favored the competition model (MacWhinney, 1997).

PMID- 29593628
TI  - Gray Matter and White Matter Abnormalities in Temporal Lobe Epilepsy Patients
      with and without Hippocampal Sclerosis.
AB  - The presentation and distribution of gray matter (GM) and white matter (WM)
      abnormalities in temporal lobe epilepsy (TLE) have been widely studied. Here, we
      investigated the GM and WM abnormalities in TLE patients with and without
      hippocampal sclerosis (HS) in five groups of participants: healthy controls (HCs)
      (n = 28), right TLE patients with HS (n = 26), right TLE patients without HS (n =
      30), left TLE patients with HS (n = 25), and left TLE patients without HS (n =
      27). We performed a flexible factorial statistical test in a whole-brain voxel
      based morphometry analysis to identify significant GM and WM abnormalities and
      analysis of variance of hippocampal and amygdala regions among the five groups
      using the FreeSurfer procedure. Furthermore, we conducted multiple regression
      analysis to assess regional GM and WM changes with disease duration. We observed
      significant ipsilateral mesiotemporal GM and WM volume reductions in TLE patients
      with HS compared with HCs. We also observed a slight GM amygdala swelling in
      right TLE patients without HS. The regression analysis revealed significant
      negative GM and WM changes with disease duration specifically in left TLE
      patients with HS. The observed GM and WM abnormalities may contribute to our
      understanding of the root of epilepsy mechanisms.

PMID- 29593629
TI  - Risk of Microangiopathy in Patients with Epilepsy under Long-term Antiepileptic
      Drug Therapy.
AB  - Background: Long-term antiepileptic drug (AED) therapy is considered a risk
      factor of atherosclerosis. Furthermore, the duration of therapy contributes to
      acceleration of large-vessel atherosclerosis. Therefore, in this study, we tested
      the hypothesis that long-term AED therapy plays a crucial role in the
      pathogenesis of microangiopathy in patients with epilepsy. Methods: We recruited
      120 patients with epilepsy (age, 18-60 years) and 40 healthy controls. Optical
      coherence tomography (OCT) was used to measure the central macular thickness and
      diameters of the retinal artery and vein to evaluate atherosclerotic retinopathy;
      microalbumin and creatinine levels in urine were assessed to evaluate
      atherosclerotic nephropathy. In addition, high-sensitivity C-reactive protein (hs
      CRP), lipid profiles, homocysteine, folate, uric acid, and body mass index were
      determined. Results: The ratio of urine albumin to creatine and OCT findings
      showed that patients with epilepsy had higher abnormal microalbuminuria and
      narrowing retinal vein diameters, respectively. Multiple linear regression
      analysis showed that increased triglyceride and hs-CRP levels might contribute to
      microalbuminuria. In addition, serum creatinine, duration of AED therapy, enzyme
      inducing AED therapy, and duration of enzyme-inducing AED therapy were candidate
      risk factors for retinal vein narrowing. Conclusion: Patients with epilepsy are
      at a higher risk for microangiopathy presented as retinopathy and nephropathy.
      Long-term AED therapy, particularly with enzyme-inducing AEDs; high triglyceride
      levels, and inflammatory processes play an important role in the development of
      microangiopathy in patients with epilepsy.

PMID- 29593630
TI  - Parkinson's Disease Dementia and Dementia with Lewy Bodies Have Similar
      Neuropsychological Profiles.
AB  - Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are common
      causes of dementia worldwide. Although considered separate entities based on the
      relative temporal onset of motor symptoms vs. diagnosis of dementia, it is
      unknown if these diseases truly have distinct cognitive profiles. We hypothesized
      that patients divided into PDD and DLB categories strictly by temporal criteria
      would have different neuropsychological profiles. We investigated this question
      via neuropsychological testing of PDD and DLB patients at the University of Iowa.
      We performed retrospective chart analysis and review of neuropsychological
      testing of clinically diagnosed patients with PDD or DLB, who had presented to
      University of Iowa's dementia and movement disorder clinics. Forty-seven patients
      diagnosed by the treating neurologist as PDD or DLB were included.
      Neuropsychological performance was compared between groups, and as a function of
      the relative timing of the motor diagnosis vs. diagnosis of dementia. We found
      that both PDD and DLB patients showed severe deficits in executive function,
      visual-spatial processing, and verbal learning. However, we found no significant
      differences in neuropsychological performance between groups, and
      neuropsychological performance could not reliably account for the relative timing
      of motor diagnosis vs. diagnosis of dementia. Our data support the idea that DLB
      and PDD are on a neuropsychological spectrum.

PMID- 29593631
TI  - Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy,
      Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel
      RANBP2 Variant.
AB  - Background: Acute hemorrhagic encephalomyelitis (AHEM) is considered as a rare
      form of acute disseminated encephalomyelitis characterized by fulminant
      encephalopathy with hemorrhagic necrosis and most often fatal outcome. Objective:
      To report the association with Ran Binding Protein (RANBP2) gene variant and the
      response to decompressive craniectomy and high-dose intravenous
      methylprednisolone (IVMP) in life-threatening AHEM. Design: Single case study.
      Case report: A 6-year-old girl known to have sickle cell disease (SCD) presented
      an acquired demyelinating syndrome (ADS) with diplopia due to sudden unilateral
      fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day). Two weeks
      after steroid weaning, she developed right hemiplegia and coma. Brain magnetic
      resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new
      multifocal areas of demyelination. She underwent decompressive craniotomy and
      evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive
      investigations ruled out vascular and infectious process. The neurological
      deterioration stopped concomitantly with combined neurosurgical drainage of the
      hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG).
      She developed during the following months Crohn disease and sclerosing
      cholangitis. After 2-year follow-up, there was no new neurological manifestation.
      The patient still suffered right hemiplegia and aphasia, but was able to walk.
      Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare
      missense variant (c.4993A>G, p.Lys1665Glu) was identified in RANBP2, a gene
      associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an
      important role in the energy homeostasis of neuronal cells. Conclusion: In any
      ADS occurring in the context of SCD and/or autoimmune condition, we recommend to
      slowly wean steroids and to closely monitor the patient after weaning to quickly
      treat any recurrence of neurological symptom with IVMP. This case report, in
      addition to others, stresses the likely efficacy of combined craniotomy, IVIG,
      and IVMP treatments in AHEM. RANBP2 mutations may sensitize the brain to
      inflammation and predispose to AHEM.

PMID- 29593632
TI  - Stroke-Related Changes in the Complexity of Muscle Activation during Obstacle
      Crossing Using Fuzzy Approximate Entropy Analysis.
AB  - This study investigated the complexity of the electromyography (EMG) of lower
      limb muscles when performing obstacle crossing tasks at different heights in
      poststroke subjects versus healthy controls. Five poststroke subjects and eight
      healthy controls were recruited to perform different obstacle crossing tasks at
      various heights (randomly set at 10, 20, and 30% of the leg's length). EMG
      signals were recorded from bilateral biceps femoris (BF), rectus femoris (RF),
      medial gastrocnemius, and tibialis anterior during obstacle crossing task. The
      fuzzy approximate entropy (fApEn) approach was used to analyze the complexity of
      the EMG signals. The fApEn values were significantly smaller in the RF of the
      trailing limb during the swing phase in poststroke subjects than healthy controls
      (p < 0.05), which may be an indication of smaller number and less frequent firing
      rates of the motor units. However, during the swing phase, there were non
      significant increases in the fApEn values of BF and RF in the trailing limb of
      the stroke group compared with those of healthy controls, resulting in a coping
      strategy when facing challenging tasks. The fApEn values that increased with
      height were found in the BF of the leading limb during the stance phase and in
      the RF of the trailing limb during the swing phase (p < 0.05). The reason for
      this may have been a larger muscle activation associated with the increase in
      obstacle height. This study demonstrated a suitable and non-invasive method to
      evaluate muscle function after a stroke.

PMID- 29593633
TI  - Quantitative Limbic System Mapping of Main Cognitive Domains in Multiple
      Sclerosis.
AB  - Background and objective: Cognitive impairment (CI) is common in multiple
      sclerosis (MS), but underlying mechanisms and their imaging correlates are not
      completely understood. The gray and white matter structures of the limbic system
      (LS) play crucial roles in different aspects of cognition. To investigate their
      role in MS related CI, and since a detailed evaluations are lacking in the
      literature, we used a comprehensive neuroimaging approach to evaluate CI's
      correlations with the main components of the LS. Methods: Ten non-cognitively
      impaired MS patients and 30 MS patients with diagnosed CI, who underwent a
      comprehensive neuropsychological evaluation were included in the analysis.
      Microstructural integrity, volumetry of main limbic gray and white matter
      structures and cortical thickness were assessed for associations with CI.
      Results: Fornix and cingulum/cingulate cortices were found to be the strongest
      correlates of CI in MS. As expected, LS' gray and white matter structures were
      involved in various cognitive functions. Uncinate fasciculi showed significant
      correlation with verbal and visuospatial learning and memory, phonemic and
      semantic fluency; hippocampi with visuospatial skills, phonemic and semantic
      fluency, executive functions, and processing speed; thalami with verbal learning,
      visuospatial skills, semantic fluency; and amygdala with verbal recognition
      discrimination. Conclusion: This comprehensive neuroimaging approach elucidated
      the role of the main limbic structures in cognitive functions associated with MS
      related CI.

PMID- 29593634
TI  - Acute Ischemic Stroke Hospital Admissions, Treatment, and Outcomes in Poland in
      2009-2013.
AB  - Introduction: Ischemic stroke (IS) still constitutes a serious problem for public
      health worldwide. The data on its burden in Poland before 2009 is limited and
      came only from a few metropolitan areas. The aims of the study were: To assess
      temporal trends in the hospital admissions, treatment, and outcomes of IS in
      Poland in 2009-2013, to identify risk factors for IS mortality and to compare the
      results with other countries. Methods: The data from the Polish Stroke Registry
      were analyzed. The data concerned all subjects hospitalized due to IS (classified
      according to the ICD10 classification as I63.0-I63.9) as primary diagnosis in
      Poland in 2009-2013. Temporal trends in treatment and outcome were analyzed.
      Hospital admissions rates as well as case fatality and 12-month mortality rates
      were calculated. Results: Altogether, 360,556 patients (47.5% of males) were
      hospitalized due to IS in Poland in 2009-2013. The median of age was 75 years,
      IQR 18 (Women 78, IQR 14 vs. Men 70, IQR 17; p < 0.001). The hospital admissions
      age-standardized annual rate for IS in Poland in 2013 was 8% lower than in 2009
      (169 vs. 157/100,000; p for trend < 0.001). In-hospital case fatality has
      slightly decreased (from 13.6% in 2009 to 12.9% in 2013; p for trend < 0.001).
      One-year posthospital mortality rate has not changed (19.3% in 2009 and 2013).
      The percentage of IS subjects treated with intravenous thrombolysis was low but
      increased from 1.7% in 2009 to 6.3% in 2013 (p for trend <0.001). Conclusion:
      Since 2009, Poland has had national epidemiological data on the hospital
      admissions, treatment, and outcomes in IS. The data indicate a slow improvement
      of in-hospital survival and suggest the need for better stroke prevention and
      further dissemination of reperfusion therapy.

PMID- 29593635
TI  - Postoperative Tinnitus After Vestibular Schwannoma Surgery Depends on
      Preoperative Tinnitus and Both Pre- and Postoperative Hearing Function.
AB  - Objective: Tinnitus is one of the most common symptoms before and/or after the
      surgical removal of a vestibular schwannoma (VS) affecting almost half of the
      patients. Although there is increasing evidence for the association of hearing
      impairment and VS-associated tinnitus, the effect of hearing deterioration due to
      surgery and its relation to the postoperative tinnitus (postTN) is poorly
      investigated. This knowledge, however, might (i) enlighten the pathophysiology of
      VS-associated tinnitus (i.e., peripheral or central origin) and (ii) improve
      preoperative patient counseling. The aim of this study was to understand the
      predisposition factors for a postTN in relation to hearing outcome after surgery.
      Methods: This retrospective study analyzed the presence of tinnitus in 208
      patients with unilateral VS before and after surgical removal. A binomial
      logistic regression was performed to ascertain the effect of pre- and
      postoperative hearing as well as age, gender, tumor side, and size, and
      intraoperative cochlear nerve resection (CNR) on the likelihood of postoperative
      VS-associated tinnitus. Results: Preoperative tinnitus was the strongest
      predictor of postTN. In addition, deterioration of functional hearing was
      increasing, while functional deafferentation (i.e., postoperative hearing loss)
      of non-functional hearing was reducing the risk of postTN. At the same time,
      patients with no preoperative tinnitus but complete hearing loss had the lowest
      risk to suffer from postTN. Patient age, gender, tumor side, and size as well as
      CNR played a subordinate role. Conclusion: While the presence of preoperative
      tinnitus was the strongest predictor of postTN, there is a distinct relationship
      between hearing outcome and postTN depending on the preoperative situation.
      Functional or anatomical deafferentation due to surgical tumor removal does not
      prevent postTN per se.

PMID- 29593636
TI  - Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal
      Neuronal Death After Transient Cerebral Ischemia.
AB  - Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased
      or dramatically reduced. TCI causes energy depletion and oxidative stress, which
      leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts
      as an inhibitor of pyruvate dehydrogenase kinase (PDK). Additionally, DCA is
      known to increase mitochondrial pyruvate uptake and promotes glucose oxidation
      during glycolysis, thus enhancing pyruvate dehydrogenase (PDH) activity. In this
      study, we investigated whether the inhibition of PDK activity by DCA, which
      increases the rate of pyruvate conversion to adenosine triphosphate (ATP),
      prevents ischemia-induced neuronal death. We used a rat model of TCI, which was
      induced by common carotid artery occlusion and hypovolemia for 7 min while
      monitoring the electroencephalography for sustained isoelectric potential. Male
      Sprague-Dawley rats were given an intraperitoneal injection of DCA (100 mg/kg)
      with pyruvate (50 mg/kg) once per day for 2 days after insult. The vehicle, DCA
      only or pyruvate on rats was injected on the same schedule. Our study
      demonstrated that the combined administration of DCA with pyruvate significantly
      decreased neuronal death, oxidative stress, microglia activation when compared
      with DCA, or pyruvate injection alone. These findings suggest that the
      administration of DCA with pyruvate may enhance essential metabolic processes,
      which in turn promotes the regenerative capacity of the post-ischemic brain.

PMID- 29593638
TI  - Tourette Syndrome: A Mini-Review.
AB  - The purpose of this mini-review is to provide the latest information on
      epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome
      (TS). The authors conducted a literature search of available sources describing
      the issue of tic disorders with special focus on TS and made a comparison and
      evaluation of relevant findings. The results of this mini-review indicate that TS
      is a complex disorder, which has a significant impact on the quality of life of
      both the patients and his/her family. Therefore, early and proper diagnosis and
      treatment are necessary in order to reduce or even eliminate both symptoms and
      social burden of the patient. This requires a multidisciplinary management
      approach in order to meet the patients' special needs. Future research should
      focus on neuroimaging, new neurotransmitter targets, in functional neurosurgery,
      as well as the effect of non-pharmacological psychotherapies for these people.

PMID- 29593639
TI  - Step by Step: Kinematics of the Reciprocal Trail Making Task Predict Slowness of
      Activities of Daily Living Performance in Alzheimer's Disease.
AB  - Dementia impairs the ability to perform everyday activities. Reduced motor
      capacity and executive functions as well as loss of memory function and forms of
      apraxia and action disorganization syndrome can be reasons for such impairments.
      In this study, an analysis of the hand trajectories during the sequential
      movements in an adapted version of the trail making task, the reciprocal trail
      making task (RTMT), was used to predict performance in activities of daily living
      (ADL) of patients suffering from mild cognitive impairment and dementia. 1
      patient with dementia of the Alzheimer's type and 15 healthy, age-matched adults
      were tested in the standardized ADL of tea making and document filing. The
      characteristics of the kinematic performance in the RTMT were assessed, and
      models of multiple linear regression were computed to predict the durations of
      the ADL. Patients showed increased trial durations (TDs) in the ADL (Cohen's d:
      tea making 1.64, document filing 1.25). Parameters and explained variability
      differed across patients and control as well as between different activities. The
      models for the patient sample were stronger and particularly high for the
      document filing task for which kinematics explained 71% of the variance
      ([Formula: see text]: tea making 0.62, document filing 0.71; both tasks combined
      patients 0.55, controls 0.25). The most relevant factors for the models were the
      TD and a parameter characterizing movement fluency and variability ("movement
      harmonicity") in the RTMT. The models of multiple linear regression suggested
      that the patients' activity of daily living performance was limited by cognitive
      demands, namely, identifying the varying targets during sequencing and the
      healthy controls' performance by their motor capacity. Such models could be used
      to estimate the severity of ADL impairments in patients.

PMID- 29593637
TI  - Structural and Functional Brain Patterns of Non-Motor Syndromes in Parkinson's
      Disease.
AB  - Parkinson's disease (PD) is a common, progressive and multisystem
      neurodegenerative disorder characterized by motor and non-motor symptoms.
      Advanced magnetic resonance imaging, positron emission tomography, and functional
      magnetic resonance imaging can render the view toward understanding the neural
      basis of these non-motor syndromes, as they help to understand the underlying
      pathophysiological abnormalities. This review provides an up-to-date description
      of structural and functional brain alterations in patients with PD with cognitive
      deficits, visual hallucinations, fatigue, impulsive behavior disorders, sleep
      disorders, and pain.

PMID- 29593640
TI  - Vestibular Dysfunction in Wernicke's Encephalopathy: Predominant Impairment of
      the Horizontal Semicircular Canals.
AB  - Background: Wernicke's encephalopathy (WE), a metabolic disorder due to thiamine
      deficiency, manifests with various neurological symptoms and signs. It has been
      known as a cause of vestibular dysfunction. Preliminary reports have proposed
      predominant involvement of the horizontal semicircular canals (HSCs). Objective:
      To better characterize the pattern of vestibular impairment in patients with WE
      using quantitative video head-impulse testing and to review the literature
      regarding this topic. Method: From January 2014 to December 2016, we
      retrospectively enrolled five cases of WE that received quantitative video-head
      impulse testing (vHIT). We retrieved the clinical features from the medical
      records and reviewed quantitative head-impulse testing (qHIT) and caloric
      irrigation. Based on the gain and the number of corrective saccades, the function
      (normal vs. impaired) of each semicircular canal was rated. In addition, we
      conducted a MEDLINE and EMBASE search to identify other published cases of WE
      that had received qHIT. Neuro-otologic and neuro-ophthalmologic findings and
      vestibular testing results were extracted. Results: A total of 17 patients (own
      series = 5; published cases = 12) aged 54.6 +/- 11 years were included. Key
      neurologic findings were ataxia of stance and gait (13/13, 100%), spontaneous
      nystagmus (7/14, 50%), gaze-evoked nystagmus (GEN) (17/17, 100%), positive
      bedside head-impulse testing for the horizontal canals (16/17, 94%), and memory
      impairment and mental changes (6/11, 54.5%). Regarding vestibular testing, qHIT
      (either video based or search-coil based) documented selective bilateral
      horizontal canal dysfunction with normal or minimal vertical canal impairment
      (14/14, 100%). On caloric irrigation, bilateral horizontal canal paresis was
      noted in most cases (10/11, 91%). Conclusion: In WE, signs of both peripheral and
      central vestibular dysfunction (i.e., GEN, ataxia of stance and gait, abnormal
      head-impulse testing) were common. Selective or predominant impairment of the
      HSCs seems to be the most common finding of WE likely related to enhanced
      vulnerability of the medial vestibular nuclei neurons to thiamine deficiency.
      Quantitative vHIT of all six semicircular canals is therefore a useful tool for
      the diagnosis and should be applied in all patients with suspected WE.

PMID- 29593641
TI  - Localization of Epileptogenic Zone With the Correction of Pathological Networks.
AB  - Patients with focal drug-resistant epilepsy are potential candidates for surgery.
      Stereo-electroencephalograph (SEEG) is often considered as the "gold standard" to
      identify the epileptogenic zone (EZ) that accounts for the onset and propagation
      of epileptiform discharges. However, visual analysis of SEEG still prevails in
      clinical practice. In addition, epilepsy is increasingly understood to be the
      result of network disorder, but the specific organization of the epileptic
      network is still unclear. Therefore, it is necessary to quantitatively localize
      the EZ and investigate the nature of epileptogenic networks. In this study,
      intracranial recordings from 10 patients were analyzed through adaptive directed
      transfer function, and the out-degree of effective network was selected as the
      principal indicator to localize the epileptogenic area. Furthermore, a coupled
      neuronal population model was used to qualitatively simulate electrical activity
      in the brain. By removing individual populations, virtual surgery adjusting the
      network organization could be performed. Results suggested that the accuracy and
      detection rate of the EZ localization were 82.86 and 85.29%, respectively. In
      addition, the same stage shared a relatively stable connectivity pattern, while
      the patterns changed with transition to different processes. Meanwhile, eight
      cases of simulations indicated that networks in the ictal stage were more likely
      to generate rhythmic spikes. This indicated the existence of epileptogenic
      networks, which could enhance local excitability and facilitate synchronization.
      The removal of the EZ could correct these pathological networks and reduce the
      amount of spikes by at least 75%. This might be one reason why accurate resection
      could reduce or even suppress seizures. This study provides novel insights into
      epilepsy and surgical treatments from the network perspective.

PMID- 29593642
TI  - Microsaccade Characteristics in Neurological and Ophthalmic Disease.
AB  - Microsaccade research has recently reached a critical mass of studies that
      allows, for the first time, a comprehensive review of how microsaccadic dynamics
      change in neurological and ophthalmic disease. We discuss the various
      pathological conditions that affect microsaccades, their impact on microsaccadic
      and other fixational eye movement dynamics, and the incipient studies that point
      to microsaccadic features as potential indicators of differential and early
      diagnoses of multiple clinical conditions, from movement disorders to attention
      deficit hyperactivity disorder to amblyopia. We propose that the objective
      assessment of fixational eye movement parameters may help refine differential
      diagnostics in neurological disease and assist in the evaluation of ongoing
      therapy regimes. In addition, determining the effects of ophthalmic disease on
      fixational eye movement features may help evaluate visual impairment in an
      objective manner, particularly in young patients or those experiencing
      communication difficulties.

PMID- 29593643
TI  - Spontaneous Nystagmus in the Dark in an Infantile Nystagmus Patient May Represent
      Negative Optokinetic Afternystagmus.
AB  - Abnormal projection of the optic nerves to the wrong cerebral hemisphere
      transforms the optokinetic system from its usual negative feedback loop to a
      positive feedback loop with characteristic ocular motor instabilities including
      directional reversal of the optokinetic nystagmus (OKN) and spontaneous
      nystagmus, which are common features of infantile nystagmus syndrome (INS).
      Visual input plays a critical role in INS linked to an underlying optic nerve
      misprojection such as that often seen in albinism. However, spontaneous nystagmus
      often continues in darkness, making the visual, sensory-driven etiology
      questionable. We propose that sensorimotor adaptation during the constant
      nystagmus of patients in the light could account for continuing nystagmus in the
      dark. The OKN is a stereotyped reflexive eye movement in response to motion in
      the surround and serves to stabilize the visual image on the retina, allowing
      high resolution vision. Robust negative optokinetic afternystagmus (negative
      OKAN), referring to the continuous nystagmus in the dark with opposite beating
      direction of the preceding OKN, has been identified in various non-foveated
      animals. In humans, a robust afternystagmus in the same direction as previous
      smooth-pursuit movements (the eye's continuous tracking and foveation of a moving
      target) induced by visual stimuli has been known to commonly mask negative OKAN.
      Some INS patients are often associated with ocular hypopigmentation, foveal
      hypoplasia, and compromised smooth pursuit. We identified an INS case with
      negative OKAN in the dark, in contrast to the positive afternystagmus in healthy
      subjects. We hypothesize that spontaneous nystagmus in the dark in INS patients
      may be attributable to sensory adaptation in the optokinetic system after a
      sustained period of spontaneous nystagmus with directional visual input in light.

PMID- 29593644
TI  - Autonomic Neuropathy-a Prospective Cohort Study of Symptoms and E/I Ratio in
      Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes.
AB  - Background: Autonomic neuropathy in diabetes, in addition to causing a range of
      symptoms originating from the autonomic nervous system, may increase
      cardiovascular morbidity. Our aim was to study the progression of autonomic
      neuropathy, based on symptom score and evaluation of an autonomic test, in
      persons with normal and impaired glucose tolerance and in patients with type 2
      diabetes (T2D). Methods: Participants were recruited in 2003/2004 with a follow
      up in 2014. The participants' glucose tolerance was categorized using oral
      glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score
      (ASS), ECG was used to test cardiac autonomic function based on the
      expiration/inspiration ratio (E/I ratio), and blood samples were taken on both
      occasions. Results: ASSs were higher at follow-up in the T2D patients than in the
      normal glucose tolerance group (mean 1.21 +/- 1.30 vs. 0.79 +/- 0.7; p < 0.05).
      E/I ratio did not deteriorate more than could be expected as an aging effect in
      well-controlled T2D. No relationship was found between E/I ratio and HbA1c or
      ASS. Conclusion: The presence of autonomic symptoms increased over time in T2D
      patients, but the symptoms did not correlate with the E/I ratio in this
      metabolically well-controlled cohort. ASSs can be a useful clinical tool when
      assessing the progression of autonomic dysfunction in patients with abnormal
      glucose metabolism.

PMID- 29593645
TI  - Editorial: Clinical and Molecular Epidemiology of Thyroid Cancer of Follicular
      Origin.

PMID- 29593647
TI  - Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum
      Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.
AB  - The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha
      (TNF-alpha) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed
      to investigate the blood serum levels of these biomarkers in colorectal adenoma.
      The case-control study consisted of serum from 180 African American patients with
      colon adenoma (cases) and 198 healthy African Americans (controls) at Howard
      University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-alpha
      detection and quantification. Statistical analysis was performed by t-test and
      multivariate logistic regression. The respective differences in median leptin,
      adiponectin, IGF-1, and TNF-alpha levels between control and case groups (13.9
      vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were
      statistically significant (P < 0.05). In a multivariate model, the odds ratio for
      adiponectin, TNF-alpha, and IGF-1 were 2.0 (95% CI = 1.6-2.5; P < 0.001), 1.5
      (95% CI = 1.5(1.1-2.0); P = 0.004), and 1.6 (95% CI = 1.3-2.0; P < 0.001),
      respectively. There was a positive correlation between serum adiponectin and IGF
      1 concentrations with age (r = 0.17, P < 0.001 and r = 0.13, P = 0.009), TNF
      alpha, IGF-1, and leptin concentration with body mass index (BMI) (r = 0.44, P <
      0.001; r = 0.11, P = 0.03; and r = 0.48, P < 0.001), respectively. Also, there
      was a negative correlation between adiponectin and leptin concentrations with BMI
      (r = -0.40, P < 0.001), respectively. These data support the hypothesis that
      adiponectin, IGF-1, and TNF-alpha high levels correlate with higher risk of colon
      adenoma and can thus be used for colorectal adenomas risk assessment.

PMID- 29593646
TI  - An Approach to Greater Specificity for Glucocorticoids.
AB  - Glucocorticoid steroids are among the most prescribed drugs each year.
      Nonetheless, the many undesirable side effects, and lack of selectivity, restrict
      their greater usage. Research to increase glucocorticoid specificity has spanned
      many years. These efforts have been hampered by the ability of glucocorticoids to
      both induce and repress gene transcription and also by the lack of success in
      defining any predictable properties that control glucocorticoid specificity.
      Correlations of transcriptional specificity have been observed with changes in
      steroid structure, receptor and chromatin conformation, DNA sequence for receptor
      binding, and associated cofactors. However, none of these studies have progressed
      to the point of being able to offer guidance for increased specificity. We
      summarize here a mathematical theory that allows a novel and quantifiable
      approach to increase selectivity. The theory applies to all three major actions
      of glucocorticoid receptors: induction by agonists, induction by antagonists, and
      repression by agonists. Simple graphical analysis of competition assays involving
      any two factors (steroid, chemical, peptide, protein, DNA, etc.) yields
      information (1) about the kinetically described mechanism of action for each
      factor at that step where the factor acts in the overall reaction sequence and
      (2) about the relative position of that step where each factor acts. These two
      pieces of information uniquely provide direction for increasing the specificity
      of glucocorticoid action. Consideration of all three modes of action indicate
      that the most promising approach for increased specificity is to vary the
      concentrations of those cofactors/pharmaceuticals that act closest to the
      observed end point. The potential for selectivity is even greater when varying
      cofactors/pharmaceuticals in conjunction with a select class of antagonists.

PMID- 29593648
TI  - Appropriate Frequency and Interval of Neck Ultrasonography Surveillance during
      the First 10 Years after Total Thyroidectomy in Patients with Papillary Thyroid
      Carcinoma.
AB  - Background: No previous study has employed the frequency and interval of follow
      up ultrasonography (US) during the first 10 years after total thyroidectomy in
      patients with papillary thyroid carcinoma (PTC). The aim of this study was to
      determine the appropriate frequency and interval of follow-up US during the first
      10 years in patients who have undergone total thyroidectomy for PTC. Methods: Two
      hundred seventy-two patients underwent total thyroidectomy for PTC at our
      institution from January 2006 to December 2007. Nineteen patients were excluded
      because of lack of US follow-up data for the neck. Follow-up US was performed by
      one of two radiologists in all patients. Tumor recurrence/persistence was
      confirmed by histopathology. Results: The mean interval between surgery and the
      final follow-up US examination was 79.0 months, and the mean number of follow-up
      US sessions was 5.9 in the 253 evaluable patients. Eleven patients (4.3%)
      developed tumor recurrence/persistence, which was detected on follow-up US within
      5 years after total thyroidectomy in all cases. T and N stages were independently
      associated with tumor recurrence/persistence. The interval between surgery and
      first suspicion of tumor recurrence/persistence on follow-up US was <=12 months
      in six patients and 20, 35, 41, 53, and 60 months in the remaining five patients.
      Conclusion: For detection of tumor recurrence/persistence after total
      thyroidectomy in patients with PTC, one or two sessions of follow-up US during
      the first 2 years, depending on T and N stages and one session of follow-up US in
      every second year during the following 8 years may be appropriate.

PMID- 29593650
TI  - Hypophysitis following Treatment with Ustekinumab: Radiological and Pathological
      Findings.
AB  - Context: Ustekinumab is a human IgG1 monoclonal antibody that targets interleukin
      (IL)-12 and IL-23, which may be useful in the treatment of autoimmune conditions
      such as psoriasis, psoriatic arthritis, and Crohn's disease. Hypophysitis is an
      immune-derived inflammatory condition of the pituitary gland that may lead to
      pituitary dysfunction. With the increasing use of immunotherapy, it is possible
      that this and other new immune-related adverse events (IRAEs) arise, although the
      mechanisms involved are still incompletely defined. Case description: A 35-year
      old male, with a previous history of severe plaque-psoriasis who had started
      treatment with ustekinumab 4 months before, complained of progressive and
      persistent headache. Brain magnetic resonance imaging (MRI) was unremarkable. One
      year later, a new MRI was performed due to headache persistence, which revealed a
      homogenous and diffuse pituitary enlargement, with suprasellar extension and
      optic chiasm involvement, blurring of the pituitary stalk, absence of clear
      differentiation between the anterior and posterior lobes, and no signs of
      hemorrhage or adenomas. Endocrine evaluation was consistent with
      panhypopituitarism. Work-up of infiltrative and infectious diseases was negative.
      Follow-up MRI revealed an increase in the pituitary enlargement and
      transsphenoidal surgery was performed. Pathological findings revealed an intense
      fibrosis and a chronic inflammatory infiltrate, but no evidence of adenoma,
      granuloma, or acid fast bacilli. Immunohistochemical staining showed a combined T
      cell (CD3+, CD4+) and B-cell (CD19+, CD20+) phenotype. Conclusion: We suggest a
      novel IRAE of ustekinumab, with full radiological and immunopathological
      iconography, which may be mediated by the complex interaction between different
      immunological processes.

PMID- 29593649
TI  - Insulin-Like Growth Factor-Binding Proteins of Teleost Fishes.
AB  - The insulin-like growth factor (Igf) binding protein (Igfbp) family has a broad
      range of physiological functions and a fascinating evolutionary history. This
      review focuses on the Igfbps of teleost fishes, where genome duplication events
      have diversified gene repertoire, function, and physiological regulation-with six
      core Igfbps expanded into a family of over twenty genes in some lineages. In
      addition to briefly summarizing the current state of knowledge on teleost Igfbp
      evolution, function, and expression-level regulation, we highlight gaps in our
      understanding and promising areas for future work.

PMID- 29593651
TI  - Distinct Shift in Beta-Cell Glutaredoxin 5 Expression Is Mediated by Hypoxia and
      Lipotoxicity Both In Vivo and In Vitro.
AB  - Histomorphological and functional alterations in pancreatic islet composition
      directly correlate with hyperglycemia severity. Progressive deterioration of
      metabolic control in subjects suffering from type 2 diabetes is predominantly
      caused by impaired beta-cell functionality. The glutaredoxin system is supposed
      to wield protective properties for beta-cells. Therefore, we sought to identify a
      correlation between the structural changes observed in diabetic pancreatic islets
      with altered glutaredoxin 5 expression, in order to determine an underlying
      mechanism of beta-cell impairment. Islets of db/db mice presenting with
      uncontrolled diabetes were assessed in terms of morphological structure and
      insulin, glucagon, and glutaredoxin 5 expression. MIN6 cell function and
      glutaredoxin 5 expression were analyzed after exposure to oleic acid and hypoxia.
      Islets of diabese mice were marked by typical remodeling and distinct reduction
      of, and shifts, in localization of glutaredoxin 5-positive cells. These islets
      featured decreased glutaredoxin 5 as well as insulin and glucagon content. In
      beta-cell culture, glutaredoxin 5 protein and mRNA expression were decreased by
      hypoxia and oleic acid but not by leptin treatment. Our study demonstrates that
      glutaredoxin 5 expression patterns are distinctively altered in islets of rodents
      presenting with uncontrolled diabesity. In vitro, reduction of islet-cell
      glutaredoxin 5 expression was mediated by hypoxia and oleic acid. Thus,
      glutaredoxin 5-deficiency in islets during diabetes may be caused by lipotoxicity
      and hypoxia.

PMID- 29593652
TI  - 11beta-HSD Types 1 and 2 in the Songbird Brain.
AB  - Glucocorticoid (GC) hormones act on the brain to regulate diverse functions, from
      behavior and homeostasis to the activity of the hypothalamic-pituitary-adrenal
      axis. Local regeneration and metabolism of GCs can occur in target tissues
      through the actions of the 11beta-hydroxysteroid dehydrogenases [11 beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and 11 beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2), respectively] to regulate access to GC
      receptors. Songbirds have become especially important model organisms for studies
      of stress hormone action; however, there has been little focus on neural GC
      metabolism. Therefore, we tested the hypothesis that 11beta-HSD1 and 11beta-HSD2
      are expressed in GC-sensitive regions of the songbird brain. Localization of
      11beta-HSD expression in these regions could provide precise temporal and spatial
      control over GC actions. We quantified GC sensitivity in zebra finch (Taeniopygia
      guttata) brain by measuring glucocorticoid receptor (GR) and mineralocorticoid
      receptor (MR) expression across six regions, followed by quantification of 11beta
      HSD1 and 11beta-HSD2 expression. We detected GR, MR, and 11beta-HSD2 mRNA
      expression throughout the adult brain. Whereas 11beta-HSD1 expression was
      undetectable in the adult brain, we detected low levels of expression in the
      brain of developing finches. Across several adult brain regions, expression of
      11beta-HSD2 covaried with GR and MR, with the exception of the cerebellum and
      hippocampus. It is possible that receptors in these latter two regions require
      direct access to systemic GC levels. Overall, these results suggest that 11beta
      HSD2 expression protects the adult songbird brain by rapid metabolism of GCs in a
      context and region-specific manner.

PMID- 29593653
TI  - Identification of Metabolomic Biomarkers for Endometrial Cancer and Its
      Recurrence after Surgery in Postmenopausal Women.
AB  - Endometrial cancer (EC) is the most frequent gynecological cancer in developed
      countries. Most EC occurs after menopause and is diagnosed as endometrioid (type
      I) carcinomas, which exhibit a favorable prognosis. In contrast, non-endometrioid
      (type II) carcinomas such as serous tumors have a poor prognosis. Our goal was to
      identify novel blood-based markers associated with EC subtypes and recurrence
      after surgery in postmenopausal women. Using mass spectrometry-based untargeted
      metabolomics, we examined preoperative serum metabolites among control women (n =
      18) and those with non-recurrent (NR) and recurrent (R) cases of type I
      endometrioid (n = 24) and type II serous (n = 12) carcinomas. R and NR cases were
      similar with respect to pathological characteristics, body mass index, and age. A
      total of 1,592 compounds were analyzed including 14 different lipid classes. When
      we compared EC cases with controls, 137 metabolites were significantly different.
      A combination of spermine and isovalerate resulted in an age-adjusted area under
      the receiver-operating characteristic curve (AUCadj) of 0.914 (P < 0.001) for EC
      detection. The combination of 2-oleoylglycerol and TAG42:2-FA12:0 allowed the
      distinction of R cases from NR cases with an AUCadj of 0.901 (P < 0.001). Type I
      R cases were also characterized by much lower levels of bile acids and elevated
      concentrations of phosphorylated fibrinogen cleavage peptide, whereas type II R
      cases displayed higher levels of ceramides. The findings from our pilot study
      provide a detailed metabolomics study of EC and identify putative serum
      biomarkers for defining clinically relevant risk groups.

PMID- 29593654
TI  - Ethnic Disparities in Endothelial Function and Its Cardiometabolic Correlates:
      The Pathobiology of Prediabetes in A Biracial Cohort Study.
AB  - Background: Endothelial function (EF) reflects the balance between vasodilatory
      and vasoconstrictive factors produced by (or acting on) the innermost lining of
      blood vessels. Endothelial dysfunction, an imbalance between these factors that
      favors vasoconstriction, has been associated with increased risk for
      cardiovascular disease. However, the influence of race/ethnicity and glycemic
      status on association between EF and cardiovascular risk factors remain to be
      clarified. Subjects and methods: We assessed EF in relation to glycemia and
      cardiometabolic profile in African-American (AA) and European-American (EA)
      offspring of parents with type 2 diabetes (T2D), who are participants in the
      prospective pathobiology and reversibility of prediabetes in a biracial cohort
      (PROP-ABC) study. Assessments at enrollment included a 75 g oral glucose
      tolerance test (OGTT), blood pressure, anthropometry, body composition (DEXA),
      and lipid profile. Other assessments were insulin sensitivity and resting energy
      expenditure. EF was measured using flow-mediated vasodilation (EndoPAT 2000) and
      expressed as reactive hyperemia index (RHI). Results: We studied 190 subjects
      (100 AA, 90 C), mean age (+/-SD) 53.1 +/- 9.1 years, and body mass index 30.6 +/-
      6.8 kg/m2. Based on OGTT data, 96 subjects (52 AA, 44 EA) had prediabetes and 94
      subjects were normoglycemic (48 AA and 46 EA). The RHI was lower in AA than EA
      (2.17 +/- 0.55 vs. 2.36 +/- 0.72, P = 0.05) and in prediabetic than normoglycemic
      subjects (2.14 +/- 0.62 vs. 2.38 +/- 0.65, P = 0.013). Using RHI <= 1.68 as
      diagnostic cut-off, 19% of participants with prediabetes and 10% of normoglycemic
      participants had endothelial dysfunction (P = 0.04). In univariate models, RHI
      was positively associated with age and HDL cholesterol levels, and inversely
      associated with adiposity, diastolic blood pressure, and 2hr plasma glucose. The
      association between RHI and adiposity was stronger in men than women. The
      association between RHI and age, glucose and HDL cholesterol displayed marked
      ethnic disparities. Conclusion: In our biracial cohort comprising offspring of
      parents with T2D, prediabetes increased the risk of endothelial dysfunction.
      However, the association between EF and cardiometabolic risk factors was
      significantly modified by ethnicity and gender. Our findings support current
      understanding of endothelial dysfunction as an early sensitive indicator of
      cardiometabolic risk.

PMID- 29593655
TI  - Pattern of Use of Biosimilar and Originator Somatropin in Italy: A Population
      Based Multiple Databases Study During the Years 2009-2014.
AB  - Purpose: Somatropin [recombinant growth hormone (rGH)] is approved in children
      and adults for several conditions involving growth disturbances and the
      corresponding biosimilar is available in Italy since 2006. No population-based
      data are available on the pattern of rGH use in Italian clinical practice. This
      study aimed at exploring the pattern of biosimilar and originator rGH use in six
      Italian centers, where different policy interventions promoted biosimilar use.
      Methods: This population-based, drug-utilization study was conducted in the years
      2009-2014, using administrative databases of Umbria, Tuscany, and Lazio Regions
      and Local Health Units of Caserta, Treviso, and Palermo. Naive rGH users were
      characterized, and prevalence of use and discontinuation were assessed over time.
      Results: Among 6,785 patients treated with rGH during the study years, 4,493
      (66.2%) were naive users (males/females = 1.3), mostly affected by GH deficiency.
      The prevalence of rGH use increased from 2009 to 2010, remaining stable
      thereafter, but it was heterogeneous across centers (twofold higher prevalence of
      use in center n.2 than centers n.4 and 1 in 2014). Biosimilar rGH uptake
      increased over time but was low (7.8% in 2014) and heterogeneous as well.
      Discontinuation of rGH therapy occurred in 54.0% of naive users, more frequently
      in females than males (58.1 vs. 50.9%). During the first year of treatment,
      discontinuation was frequent (39.9%), but no statistically significant
      differences were observed in treatment persistence for biosimilar vs. originator
      rGH (p > 0.05). Conclusion: Geographical heterogeneity in the prevalence of rGH
      use was observed. Similarly, the biosimilar rGH uptake was low and variable
      across centers. Post-marketing monitoring is required to continuously monitor the
      benefit-risk profile of rGH, thus guaranteeing greater savings than only
      promoting lowest cost rGH.

PMID- 29593656
TI  - Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors
      for Gestational Diabetes Mellitus.
AB  - Certain phthalates and bisphenol A (BPA) have been associated with insulin
      resistance and type 2 diabetes in non-pregnant adults, but studies of gestational
      diabetes mellitus (GDM) have reported conflicting results for phthalates and no
      associations with BPA. Our aim was to investigate the relationship between
      maternal serum levels of phthalate metabolites and phenols at 10-17 weeks of
      gestation and glucose homeostasis at 28 weeks of gestation. 232 women aged >=16
      years without type 1 or 2 diabetes with singleton male pregnancies were recruited
      from a single UK maternity centre between 2001 and 2009 as part of a prospective
      observational study (Cambridge Baby Growth Study). Serum levels of 16 phthalate
      metabolites and 9 phenols (including BPA) were measured using liquid
      chromatography/tandem mass spectrometry. Oral glucose tolerance tests were
      performed at 28 weeks. 47/232 (20.3%) women had GDM. First-trimester triclosan
      (TCS) was inversely associated with incident GDM (adjusted odds ratio per log
      increase in concentration 0.54, 95% confidence interval 0.34-0.86, p = 0.010).
      Amongst women without GDM, first-trimester mono-(2-ethylhexyl) phthalate and
      mono(carboxyisooctyl) phthalate levels were positively associated with 120-min
      plasma glucose (adjusted beta 0.268 and 0.183, p = 0.0002 and 0.010,
      respectively) in mid-pregnancy. No other monotonic associations were detected
      between phthalate or phenol levels and fasting or stimulated plasma glucose, beta
      cell function, insulin resistance, or 60-min disposition index. Our results
      support a glycaemia-raising effect of phthalates during pregnancy, consistent
      with findings in non-pregnant populations and suggest a possible protective
      effect of exposure to TCS against GDM.

PMID- 29593657
TI  - Lipoprotein Lipase Expression in Hypothalamus Is Involved in the Central
      Regulation of Thermogenesis and the Response to Cold Exposure.
AB  - Lipoprotein lipase (LPL) is expressed in different areas of the brain, including
      the hypothalamus and plays an important role in neural control of the energy
      balance, including feeding behavior and metabolic fluxes. This study tested the
      hypothesis that hypothalamic LPL participates in the control of body temperature.
      We first showed that cold exposure induces decreased activity and expression of
      LPL in the mouse hypothalamus. We then selectively deleted LPL in the mediobasal
      hypothalamus (MBH) through an adeno-associated virus approach in LPL-floxed mice
      and generated MBHDelta Lpl mice with 30-35% decrease in hypothalamic LPL
      activity. Results showed a decrease in body temperature in MBHDelta Lpl mice when
      compared with controls at 22 degrees C. Exposure to cold (4 degrees C for 4 h)
      decreased the body temperature of the control mice while that of the MBHDelta Lpl
      mice remained similar to that observed at 22 degrees C. MBHDelta Lpl mice also
      showed increased energy expenditure during cold exposure, when compared to
      controls. Finally, the selective MBH deletion of LPL also increased the
      expression of the thermogenic PRMD16 and Dio2 in subcutaneous and perigonadal
      adipose tissues. Thus, the MBH LPL deletion seems to favor thermogenesis. These
      data demonstrate that for the first time hypothalamic LPL appears to function as
      a regulator of body temperature and cold-induced thermogenesis.

PMID- 29593658
TI  - Economic Evaluation of PRIMROSE-A Trial-Based Analysis of an Early Childhood
      Intervention to Prevent Obesity.
AB  - Background: Childhood obesity is a major clinical and economic health concern.
      Alongside the clinical understanding of obesity, there is a growing interest in
      designing and implementing interventions that are worth their money given the
      scarce resources in the health care sector. This study is one of the first
      efforts to provide evidence by assessing the effects and costs of a population
      based primary prevention intervention targeting pre-school children attending
      child health centers in Sweden. Methods: The economic evaluation is based on the
      PRIMROSE cluster-randomized controlled trial aiming to establish healthy eating
      and physical activity among pre-school children (9-48 months of age) through
      motivational interviewing applied by trained nurses at child health centers. The
      cost-effectiveness is assessed over the trial period from a societal perspective.
      The primary outcome was BMI at age 4. Cost data was prospectively collected
      alongside the trial. Scenario analyses were carried out to identify uncertainty.
      Results: The estimated additional mean total costs of the PRIMROSE intervention
      were 342 Euro (95% CI: 334; 348) per child. During pre-school years direct costs
      mainly consist of training costs and costs for the additional time used by nurses
      to implement the intervention compared to usual care. Early indirect costs mainly
      consist of parents' absence from work due to their participation in the
      intervention. The incremental cost-effectiveness ratio in the base case analysis
      was 3,109 Euro per 1 BMI unit prevented. Conclusion: We cannot provide evidence
      that the PRIMROSE intervention is cost-effective, given the uncertainty in the
      effect measure. Until further evidence is provided, we recommend resources to be
      spent elsewhere within the field of obesity prevention. Furthermore, to achieve
      valid and reliable cost-effectiveness results, the economic evaluation of obesity
      prevention programs in early childhood should incorporate the life time impact to
      capture all relevant costs and benefits.

PMID- 29593660
TI  - Genetic Platforms of blaCTX-M in Carbapenemase-Producing Strains of K. pneumoniae
      Isolated in Chile.
AB  - Objective: To elucidate whether the genetic platforms of blaCTX-M contribute to
      the phenotypes of multi-drug-resistance (MDR) in the first carbapenemase
      producing K. pneumoniae strains isolated in Chile. Method: Twenty-two
      carbapenemase-producing K. pneumoniae strains isolated from different Chilean
      patients and hospitals were studied. Their genetic relatedness was assessed by
      PFGE and MLST. The levels of antibiotic resistance were evaluated by determining
      the minimum inhibitory concentration of various antimicrobials. In addition,
      several antibiotic resistance genes of clinical relevance in Chile were
      investigated. The prevalence, allelic variants, and genetic platforms of blaCTX-M
      were determined by PCR and sequencing. Results: Out of the 22 strains studied, 20
      carry KPC, one carries NDM-1, and one carries OXA-370. The PFGE analysis showed
      three clades with a genetic relatedness >85%, two formed by four strains and one
      by eight strains. The other strains are not genetically related, and a total of
      17 different pulse types were detected. Ten different STs were identified, the
      main ones being ST258 (five strains) and ST1161 (seven strains). The isolates
      presented different percentages of resistance, and 82% were resistant to all the
      beta-lactams tested, 91% to ciprofloxacin, 73% to colistin, 59% to gentamicin,
      50% to amikacin, and only 9% to tigecycline. All isolates carried blaTEM and
      blaSHV, whereas 71% carried aac(6')Ib-cr, and 57% one qnr gene (A, B, C, D, or
      S). The blaCTX-M gene was found in 10 of the isolates (4 blaCTX-M-15 and 6 blaCTX
      M-2). The characterization of the platform, in seven selected strains, revealed
      that the gene is associated with unusual class 1 integrons and insertion
      sequences such as ISCR1, ISECp1, and IS26. Conclusion: In the first carbapenemase
      producing K. pneumoniae strains isolated in Chile the genetic platform of blaCTX
      M-2 corresponds to an unusual class 1 integron that can be responsible for the
      MDR phenotype, whereas the genetic platforms of blaCTX-M-15 are associated with
      different IS and do not contribute to multi-drug resistance.

PMID- 29593659
TI  - How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection
      Using Antiviral Therapy.
AB  - Five to ten million individuals are infected by Human T-cell Leukemia Virus type
      1 (HTLV-1). HTLV-1 is transmitted through prolonged breast-feeding, by sexual
      contacts and by transmission of infected T lymphocytes through blood transfusion.
      One to ten percent of infected carriers will develop a severe HTLV-1-associated
      disease: Adult-T-cell leukemia/lymphoma (ATLL), or a neurological disorder named
      Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). In vivo,
      HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells
      and dendritic cells. There is a strong correlation between HTLV-1 proviral load
      (PVL) and clinical status of infected individuals. Thus, reducing PVL could be
      part of a strategy to prevent or treat HTLV-1-associated diseases among carriers.
      Treatment of ATLL patients using conventional chemotherapy has very limited
      benefit. Some chronic and acute ATLL patients are, however, efficiently treated
      with a combination of interferon alpha and zidovudine (IFN-alpha/AZT), to which
      arsenic trioxide is added in some cases. On the other hand, no efficient
      treatment for TSP/HAM patients has been described yet. It is therefore crucial to
      develop therapies that could either prevent the occurrence of HTLV-1-associated
      diseases or at least block the evolution of the disease in the early stages. In
      vivo, reverse transcriptase (RT) activity is low in infected cells, which is
      correlated with a clonal mode of viral replication. This renders infected cells
      resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase
      inhibitors (HDACi) associated to AZT efficiently induces viral expression and
      prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human
      primates, HDACi/AZT combination allows a strong decrease in the PVL.
      Unfortunately, rebound in the PVL occurs when the treatment is stopped,
      highlighting the need for better antiviral compounds. Here, we review previously
      used strategies targeting HTLV-1 replication. We also tested a series of HIV-1 RT
      inhibitors in an in vitro anti-HTLV-1 screen, and report that bis-POM-PMEA
      (adefovir dipivoxil) and bis-POC-PMPA (tenofovir disoproxil) are much more
      efficient compared to AZT to decrease HTLV-1 cell-to-cell transmission in vitro.
      Our results suggest that revisiting already established antiviral drugs is an
      interesting approach to discover new anti-HTLV-1 drugs.

PMID- 29593661
TI  - Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia
      in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation
      and Comparative Phylogenetic Analysis.
AB  - Francisella (F.) tularensis is a highly virulent, Gram-negative bacterial
      pathogen and the causative agent of the zoonotic disease tularemia. Here, we
      generated, analyzed and characterized a high quality circular genome sequence of
      the F. tularensis subsp. holarctica strain 12T0050 that caused fatal tularemia in
      a hare. Besides the genomic structure, we focused on the analysis of oriC, unique
      to the Francisella genus and regulating replication in and outside hosts and the
      first report on genomic DNA methylation of a Francisella strain. The high quality
      genome was used to establish and evaluate a diagnostic whole genome sequencing
      pipeline. A genotyping strategy for F. tularensis was developed using various
      bioinformatics tools for genotyping. Additionally, whole genome sequences of F.
      tularensis subsp. holarctica isolates isolated in the years 2008-2015 in Germany
      were generated. A phylogenetic analysis allowed to determine the genetic
      relatedness of these isolates and confirmed the highly conserved nature of F.
      tularensis subsp. holarctica.

PMID- 29593662
TI  - Petrophilic, Fe(III) Reducing Exoelectrogen Citrobacter sp. KVM11, Isolated From
      Hydrocarbon Fed Microbial Electrochemical Remediation Systems.
AB  - Exoelectrogenic biofilms capable of extracellular electron transfer are important
      in advanced technologies such as those used in microbial electrochemical
      remediation systems (MERS) Few bacterial strains have been, nevertheless,
      obtained from MERS exoelectrogenic biofilms and characterized for bioremediation
      potential. Here we report the identification of one such bacterial strain,
      Citrobacter sp. KVM11, a petrophilic, iron reducing bacterial strain isolated
      from hydrocarbon fed MERS, producing anodic currents in microbial electrochemical
      systems. Fe(III) reduction of 90.01 +/- 0.43% was observed during 5 weeks of
      incubation with Fe(III) supplemented liquid cultures. Biodegradation screening
      assays showed that the hydrocarbon degradation had been carried out by
      metabolically active cells accompanied by growth. The characteristic feature of
      diazo dye decolorization was used as a simple criterion for evaluating the
      electrochemical activity in the candidate microbe. The electrochemical activities
      of the strain KVM11 were characterized in a single chamber fuel cell and three
      electrode electrochemical cells. The inoculation of strain KVM11 amended with
      acetate and citrate as the sole carbon and energy sources has resulted in an
      increase in anodic currents (maximum current density) of 212 +/- 3 and 359 +/-
      mA/m2 with respective coulombic efficiencies of 19.5 and 34.9% in a single
      chamber fuel cells. Cyclic voltammetry studies showed that anaerobically grown
      cells of strain KVM11 are electrochemically active whereas aerobically grown
      cells lacked the electrochemical activity. Electrobioremediation potential of the
      strain KVM11 was investigated in hydrocarbonoclastic and dye detoxification
      conditions using MERS. About 89.60% of 400 mg l-1 azo dye was removed during the
      first 24 h of operation and it reached below detection limits by the end of the
      batch operation (60 h). Current generation and biodegradation capabilities of
      strain KVM11 were examined using an initial concentration of 800 mg l-1 of diesel
      range hydrocarbons (C9-C36) in MERS (maximum currentdensity 50.64 +/- 7 mA/m2;
      power density 4.08 +/- 2 mW/m2, 1000 omega, hydrocarbon removal 60.14 +/- 0.7%).
      Such observations reveal the potential of electroactive biofilms in the
      simultaneous remediation of hydrocarbon contaminated environments with generation
      of energy.

PMID- 29593663
TI  - Editorial: Game Changer - Next Generation Sequencing and Its Impact on Food
      Microbiology.

PMID- 29593664
TI  - Comparative Genomics and Biosynthetic Potential Analysis of Two Lichen-Isolated
      Amycolatopsis Strains.
AB  - Actinomycetes have been extensively exploited as one of the most prolific
      secondary metabolite-producer sources and continue to be in the focus of interest
      in the constant search of novel bioactive compounds. The availability of less
      expensive next generation genome sequencing techniques has not only confirmed the
      extraordinary richness and broad distribution of silent natural product
      biosynthetic gene clusters among these bacterial genomes, but also has allowed
      the incorporation of genomics in bacterial taxonomy and systematics. As part of
      our efforts to isolate novel strains from unique environments, we explored lichen
      associated microbial communities as unique assemblages to be studied as potential
      sources of novel bioactive natural products with application in biotechnology and
      drug discovery. In this work, we have studied the whole genome sequences of two
      new Amycolatopsis strains (CA-126428 and CA-128772) isolated from tropical
      lichens, and performed a comparative genomic analysis with 41 publicly available
      Amycolatopsis genomes. This work has not only permitted to infer and discuss
      their taxonomic position on the basis of the different phylogenetic approaches
      used, but has also allowed to assess the richness and uniqueness of the
      biosynthetic pathways associated to primary and secondary metabolism, and to
      provide a first insight on the potential role of these bacteria in the lichen
      associated microbial community.

PMID- 29593665
TI  - Impact of Branched-Chain Amino Acid Catabolism on Fatty Acid and Alkene
      Biosynthesis in Micrococcus luteus.
AB  - Micrococcus luteus naturally produces alkenes, unsaturated aliphatic
      hydrocarbons, and represents a promising host to produce hydrocarbons as
      constituents of biofuels and lubricants. In this work, we identify the genes for
      key enzymes of the branched-chain amino acid catabolism in M. luteus, whose first
      metabolic steps lead also to the formation of primer molecules for branched-chain
      fatty acid and olefin biosynthesis, and demonstrate how these genes can be used
      to manipulate the production of specific olefins in this organism. We constructed
      mutants of several gene candidates involved in the branched-chain amino acid
      metabolism or its regulation and investigated the resulting changes in the
      cellular fatty acid and olefin profiles by GC/MS. The gene cluster encoding the
      components of the branched-chain alpha-keto acid dehydrogenase (BCKD) complex was
      identified by deletion and promoter exchange mutagenesis. Overexpression of the
      BCKD gene cluster resulted in about threefold increased olefin production whereas
      deletion of the cluster led to a drastic reduction in branched-chain fatty acid
      content and a complete loss of olefin production. The specificities of the acyl
      CoA dehydrogenases of the branched amino acid degradation pathways were deduced
      from the fatty acid and olefin profiles of the respective deletion mutant
      strains. In addition, growth experiments with branched amino acids as the only
      nitrogen source were carried out with the mutants in order to confirm our
      annotations. Both the deletion mutant of the BCKD complex, responsible for the
      further degradation of all three branched-chain amino acids, as well as the
      deletion mutant of the proposed isovaleryl-CoA dehydrogenase (specific for
      leucine degradation) were not able to grow on leucine in contrast to the parental
      strain. In conclusion, our experiments allow the unambigous assignment of
      specific functions to the genes for key enzymes of the branched-chain amino acid
      metabolism of M. luteus. We also show how this knowledge can be used to engineer
      the isomeric composition and the chain lengths of the olefins produced by this
      organism.

PMID- 29593666
TI  - Factors Involved in the Persistence of a Shiga Toxin-Producing Escherichia coli
      O157:H7 Strain in Bovine Feces and Gastro-Intestinal Content.
AB  - Healthy cattle are the primary reservoir for O157:H7 Shiga toxin-producing E.
      coli responsible for human food-borne infections. Because farm environment acts
      as a source of cattle contamination, it is important to better understand the
      factors controlling the persistence of E. coli O157:H7 outside the bovine gut.
      The E. coli O157:H7 strain MC2, identified as a persistent strain in French
      farms, possessed the characteristics required to cause human infections and
      genetic markers associated with clinical O157:H7 isolates. Therefore, the
      capacity of E. coli MC2 to survive during its transit through the bovine gastro
      intestinal tract (GIT) and to respond to stresses potentially encountered in
      extra-intestinal environments was analyzed. E. coli MC2 survived in rumen fluids,
      grew in the content of posterior digestive compartments and survived in bovine
      feces at 15 degrees C predicting a successful transit of the bacteria along the
      bovine GIT and its persistence outside the bovine intestine. E. coli MC2
      possessed the genetic information encoding 14 adherence systems including
      adhesins with properties related to colonization of the bovine intestine (F9
      fimbriae, EhaA and EspP autotransporters, HCP pilus, FdeC adhesin) reflecting the
      capacity of the bacteria to colonize different segments of the bovine GIT. E.
      coli MC2 was also a strong biofilm producer when incubated in fecal samples at
      low temperature and had a greater ability to form biofilms than the bovine
      commensal E. coli strain BG1. Furthermore, in contrast to BG1, E. coli MC2
      responded to temperature stresses by inducing the genes cspA and htrA during its
      survival in bovine feces at 15 degrees C. E. coli MC2 also activated genes that
      are part of the GhoT/GhoS, HicA/HicB and EcnB/EcnA toxin/antitoxin systems
      involved in the response of E. coli to nutrient starvation and chemical stresses.
      In summary, the large number of colonization factors known to bind to intestinal
      epithelium and to biotic or abiotic surfaces, the capacity to produce biofilms
      and to activate stress fitness genes in bovine feces could explain the
      persistence of E. coli MC2 in the farm environment.

PMID- 29593667
TI  - Amplicon Sequencing Reveals Microbiological Signatures in Spent Nuclear Fuel
      Storage Basins.
AB  - Water quality is an important determinant for the structural integrity of alloy
      cladded fuels and assemblies during long-term wet storage. Detailed
      characterization of a water filled storage basin for spent nuclear reactor fuel
      was performed following the formation and proliferation of an amorphous white
      flocculent. White precipitant was sampled throughout the storage basin for
      chemical and spectroscopic characterization, and environmental DNA was extracted
      for 454 pyrosequencing of bacterial 16S rRNA gene diversity. Accordingly,
      spectroscopic analyses indicated the precipitant to be primarily amorphous to
      crystalline aluminum (oxy) hydroxides with minor associated elemental components
      including Fe, Si, Ti, and U. High levels of organic carbon were co-localized with
      the precipitant relative to bulk dissolved organic concentrations. Bacterial
      densities were highly variable between sampling locations and with depth within
      the water filled storage basin; cell numbers ranged from 4 * 103to 4 * 104
      cells/mL. Bacterial diversity that was physically associated with the aluminum
      (oxy) hydroxide complexes exceeded an estimated 4,000 OTUs/amplicon library (3%
      cutoff) and the majority of sequences were aligned to the families
      Burkholderiaceae (23%), Nitrospiraceae (23%), Hyphomicrobiaceae (17%), and
      Comamonadaceae (6%). We surmise that episodic changes in the physical and
      chemical properties of the basin contribute to the polymerization of aluminum
      (oxy) hydroxides, which in turn can chemisorb nutrients, carbon ligands and
      bacterial cells from the surrounding bulk aqueous phase. As such, these
      precipitants should establish favorable microhabitats for bacterial colonization
      and growth. Comparative analyses of 16S rRNA gene amplicon libraries across a
      selection of natural and engineered aquatic ecosystems were performed and
      microbial community and taxonomic signatures unique to the spent nuclear fuel
      (SNF) storage basin environment were revealed. These insights could spur the
      development of tractable bio-indicators that are specific of and diagnostic for
      water quality at discrete locations and finer scales of resolution, marking an
      important contribution for improved water quality and management of SNF storage
      facilities.

PMID- 29593668
TI  - Simulation Study of cDNA Dataset to Investigate Possible Association of
      Differentially Expressed Genes of Human THP1-Monocytic Cells in Cancer
      Progression Affected by Bacterial Shiga Toxins.
AB  - Shiga toxin (Stxs) is a family of structurally and functionally related bacterial
      cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group
      of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively.
      Until recently, it has been thought that Stxs only inhibits the protein synthesis
      and induces expression to a limited number of genes in host cells, but recent
      data showed that Stxs can trigger several signaling pathways in mammalian cells
      and activate cell cycle and apoptosis. To explore the changes in gene expression
      induced by Stxs that have been shown in other systems to correlate with cancer
      progression, we performed the simulated analysis of cDNA dataset and found
      differentially expressed genes (DEGs) of human THP1-monocytic cells treated with
      Stxs. In this study, the entire data (treated and untreated replicates) was
      analyzed by statistical algorithms implemented in Bioconductor packages. The
      output data was validated by the k-fold cross technique using generalized linear
      Gaussian models. A total of 50 DEGs were identified. 7 genes including TSLP, IL6,
      GBP1, CD274, TNFSF13B, OASL, and PNPLA3 were considerably (<0.00005) related to
      cancer proliferation. The functional enrichment analysis showed 6 down-regulated
      and 1 up-regulated genes. Among these DEGs, IL6 was associated with several
      cancers, especially with leukemia, lymphoma, lungs, liver and breast cancers. The
      predicted regulatory motifs of these genes include conserved RELA, STATI, IRFI,
      NF-kappaB, PEND, HLF, REL, CEBPA, DI_2, and NFKB1 transcription factor binding
      sites (TFBS) involved in the complex biological functions. Thus, our findings
      suggest that Stxs has the potential as a valuable tool for better understanding
      of treatment strategies for several cancers.

PMID- 29593669
TI  - Assessment of Fecal Indicator Bacteria and Potential Pathogen Co-Occurrence at a
      Shellfish Growing Area.
AB  - Routine monitoring of shellfish growing waters for bacteria indicative of human
      sewage pollution reveals little about the bacterial communities that co-occur
      with these indicators. This study investigated the bacterial community, potential
      pathogens, and fecal indicator bacteria in 40 water samples from a shellfish
      growing area in the Chesapeake Bay, USA. Bacterial community composition was
      quantified with deep sequencing of 16S rRNA gene amplicons, and absolute gene
      abundances were estimated with an internal standard (Thermus thermophilus
      genomes). Fecal coliforms were quantified by culture, and Vibrio vulnificus and
      V. parahaemolyticus with quantitative PCR. Fecal coliforms and V. vulnificus were
      detected in most samples, and a diverse assemblage of potential human pathogens
      were detected in all samples. These taxa followed two general patterns of
      abundance. Fecal coliforms and 16S rRNA genes for Enterobacteriaceae, Aeromonas,
      Arcobacter, Staphylococcus, and Bacteroides increased in abundance after a 1.3
      inch rain event in May, and, for some taxa, after smaller rain events later in
      the season, suggesting that these are allochthonous organisms washed in from
      land. Clostridiaceae and Mycobacterium 16S rRNA gene abundances increased with
      day of the year and were not positively related to rainfall, suggesting that
      these are autochthonous organisms. Other groups followed both patterns, such as
      Legionella. Fecal coliform abundance did not correlate with most other taxa, but
      were extremely high following the large rainstorm in May when they co-occurred
      with a broad range of potential pathogen groups. V. vulnificus were absent during
      the large rainstorm, and did not correlate with 16S rRNA abundances of Vibrio
      spp. or most other taxa. These results highlight the complex nature of bacterial
      communities and the limited utility of using specific bacterial groups as
      indicators of pathogen presence.

PMID- 29593670
TI  - Porcine Circovirus-Like Virus P1 Inhibits Wnt Signaling Pathway in Vivo and in
      Vitro.
AB  - Porcine circovirus-like virus P1 is an important pathogen of the current pig
      industry, the infection mechanism is not entirely clear. Wnt signaling pathway
      plays an important role in the growth of young animals and infection of some
      viruses. This study was designed to demonstrate the effects of P1 infection on
      the Wnt signaling pathway. In vivo experiments, we demonstrated the down
      regulatory effects of P1 infection in piglets and mice on the downstream
      components expression levels of Wnt signaling pathway, and the effects of Wnt
      signaling pathway activation on the pathogenesis of P1. In vitro studies, we
      found P1 infection down-regulated protein level of beta-catenin and mRNA level of
      mmp2, prevented the beta-catenin from entering into nucleus, abolished the
      TCF/LEF promoter activity, proved that P1 could inhibit the activation of Wnt
      signaling pathway in vitro. Finally, we found that VP1 of P1 virus also had the
      inhibitory effects on Wnt signaling pathway in vitro, elucidated the mechanism of
      P1's inhibitory effects on the Wnt signaling pathway and offered the possibility
      that the suppression of Wnt signaling pathway was involved in the post-weaning
      multisystemic wasting syndrome (PMWS), laying a foundation for elucidating the
      pathogenesis of P1.

PMID- 29593671
TI  - The Hemagglutinin-Neuraminidase (HN) Head Domain and the Fusion (F) Protein Stalk
      Domain of the Parainfluenza Viruses Affect the Specificity of the HN-F
      Interaction.
AB  - Membrane fusion by the parainfluenza viruses is induced by virus-specific
      functional interaction between the attachment protein (HN) and the fusion (F)
      protein. This interaction is thought to be mediated by transient contacts between
      particular amino acids in the HN stalk domain and those in the F head domain.
      However, we recently reported that replacement of specified amino acids at or
      around the dimer interface of the HN head domain remarkably affected the F
      protein specificity. We then intended to further investigate this issue in the
      present study and revealed that the HPIV2 HN protein can be converted to an SV41
      HN-like protein by substituting at least nine amino acids in the HPIV2 HN head
      domain with the SV41 HN counterparts in addition to the replacement of the stalk
      domain, indicating that specified amino acids in the HN head domain play very
      important roles in determining the specificity of the HN-F interaction. On the
      other hand, we previously reported that the PIV5 F protein can be converted to an
      SV41 F-like protein by replacing 21 amino acids in the head domain of the PIV5 F
      protein with those of the SV41 F protein. We then intended to further investigate
      this issue in the present study and found that replacement of 15 amino acids in
      the stalk domain in addition to the replacement of the 21 amino acids in the head
      domain of the PIV5 F protein resulted in creation of a more SV41 F-like protein,
      indicating that specified amino acids in the F stalk domain play important roles
      in determining the specificity of the HN-F interaction. These results suggest
      that the conformations of the HN stalk domain and the F head domain are dependent
      on the structures of the HN head domain and the F stalk domain, respectively.
      Presumably, the conformations of the former domains, which are considered
      directly involved in the HN-F interaction, can be modified by subtle changes in
      the structure of the latter domains, resulting in an altered specificity for the
      interacting partners.

PMID- 29593672
TI  - Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and
      Replication.
AB  - Hepatitis C virus (HCV) preferentially replicates in the human liver and
      frequently causes chronic infection, often leading to cirrhosis and liver cancer.
      HCV is an enveloped virus classified in the genus Hepacivirus in the family
      Flaviviridae and has a single-stranded RNA genome of positive orientation. The
      HCV RNA genome is translated and replicated in the cytoplasm. Translation is
      controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated
      region (5' UTR), while also downstream elements like the cis-replication element
      (CRE) in the coding region and the 3' UTR are involved in translation regulation.
      The cis-elements controlling replication of the viral RNA genome are located
      mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding
      region, and in part these signals overlap with the signals controlling RNA
      translation. Many long-range RNA-RNA interactions (LRIs) are predicted between
      different regions of the HCV RNA genome, and several such LRIs are actually
      involved in HCV translation and replication regulation. A number of RNA cis
      elements recruit cellular RNA-binding proteins that are involved in the
      regulation of HCV translation and replication. In addition, the liver-specific
      microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA
      genome as well as to at least three additional target sites in the coding region
      and the 3' UTR. It is involved in the regulation of HCV RNA stability,
      translation and replication, thereby largely contributing to the hepatotropism of
      HCV. However, we are still far from completely understanding all interactions
      that regulate HCV RNA genome translation, stability, replication and
      encapsidation. In particular, many conclusions on the function of cis-elements in
      HCV replication have been obtained using full-length HCV genomes or near-full
      length replicon systems. These include both genome ends, making it difficult to
      decide if a cis-element in question acts on HCV replication when physically
      present in the plus strand genome or in the minus strand antigenome. Therefore,
      it may be required to use reduced systems that selectively focus on the analysis
      of HCV minus strand initiation and/or plus strand initiation.

PMID- 29593674
TI  - Metabolic Adaptation of Methanogens in Anaerobic Digesters Upon Trace Element
      Limitation.
AB  - Anaerobic digestion (AD) is a complex multi-stage process relying on the activity
      of highly diverse microbial communities including hydrolytic, acidogenic and
      syntrophic acetogenic bacteria as well as methanogenic archaea. The lower
      diversity of methanogenic archaea compared to the bacterial groups involved in AD
      and the corresponding lack of functional redundancy cause a stronger
      susceptibility of methanogenesis to unfavorable process conditions such as trace
      element (TE) deprivation, thus controlling the stability of the overall process.
      Here, we investigated the effects of a slowly increasing TE deficit on the
      methanogenic community function in a semi-continuous biogas process. The aim of
      the study was to understand how methanogens in digester communities cope with TE
      limitation and sustain their growth and metabolic activity. Two lab-scale biogas
      reactors fed with distillers grains and supplemented with TEs were operated in
      parallel for 76 weeks before one of the reactors was subjected to TE deprivation,
      leading to a decline of cobalt and molybdenum concentrations from 0.9 to 0.2
      mg/L, nickel concentrations from 2.9 to 0.8 mg/L, manganese concentrations from
      38 to 18 mg/L, and tungsten concentrations from 1.4 to 0.2 mg/L. Amplicon
      sequencing of mcrA genes revealed Methanosarcina (72%) and Methanoculleus (23%)
      as the predominant methanogens in the undisturbed reactors. With increasing TE
      limitation, the relative abundance of Methanosarcina dropped to 67% and a slight
      decrease of acetoclastic methanogenic activity was observed in batch tests with
      13C-methyl-labeled acetate, suggesting a shift toward syntrophic acetate
      oxidation coupled to hydrogenotrophic methanogenesis. Metaproteome analysis
      revealed abundance shifts of the enzymes involved in methanogenic pathways.
      Proteins involved in methylotrophic and acetoclastic methanogenesis decreased in
      abundance while formylmethanofuran dehydrogenase from Methanosarcinaceae
      increased, confirming our hypothesis of a shift from acetoclastic to
      hydrogenotrophic methanogenesis by Methanosarcina. Both Methanosarcina and
      Methanoculleus increased the abundance of N5-methyltetrahydromethanopterin
      coenzyme M methyltransferase and methyl-coenzyme M reductase. However, these
      efforts to preserve the ion motive force for energy conservation were seemingly
      more successful in Methanoculleus. We conclude that both methanogenic genera use
      different strategies to stabilize their energy balance under TE limitation.
      Methanosarcina switched from TE expensive pathways (methylotrophic and
      acetoclastic methanogenesis) to hydrogenotrophic methanogenesis. Methanoculleus
      showed a higher robustness and was favored over the more fastidious
      Methanosarcina, thus stabilizing reactor performance under TE limitation.

PMID- 29593675
TI  - Cryptococcal Antigen Screening in Asymptomatic HIV-Infected Antiretroviral Naive
      Patients in Cameroon and Evaluation of the New Semi-Quantitative Biosynex
      CryptoPS Test.
AB  - Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related
      mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts
      development of CM in antiretroviral (ART) naive HIV-infected patients with severe
      immune depression. Systematic pre-ART CrAg screening and pre-emptive oral
      fluconazole is thus recommended. We postulated that a semi-quantitative CrAg
      screening approach could offer clinically relevant advantages. Methods: ART-naive
      asymptomatic adult outpatients with <100 CD4 cells/mm3 presenting to the Yaounde
      Central Hospital, Cameroon were screened for CrAg using the IMMY lateral flow
      assay (LFA). CrAg positive patients were consented for lumbar puncture and those
      with proven CM were treated with combination antifungal therapy and those with no
      CM were offered long-term oral fluconazole. Simultaneous on-site evaluation of
      CrAg detection using the new LFA Biosynex(r) CryptoPS test was performed and both
      tests were subsequently compared to a reference commercialized CrAg enzyme
      immunoassay (EIA). Results: Prevalence of serum CrAg in 186 screened adults was
      7.5% (95%CI: 4.5-12.4). In CrAg positive patients, CM prevalence was 45.5%
      (95%CI: 18.3-75.7). IMMY and Biosynex CryptoPS strongly agreed in serum, plasma,
      and cerebrospinal fluid (Kappa: 98.4, 99.5, 100%, respectively, p < 0.001), and
      disagreed in urine (29 isolated positive CrAg in urine with IMMY, none with
      Biosynex and none of whom had proven CM). Compared to EIA, serum specificities
      were 96.6 and 98.3%, respectively. With Biosynex CryptoPS, all CM patients were
      serum T2-band positive compared to nonewithout CM. Median EIA reciprocal titre
      was 160 (IQR: 13.5-718.8) and titres >160 strongly correlated with proven CM and
      Biosynex CryptoPS T2-band positivity. During the 1-year follow up period, there
      was no incident case of CM among screened patients and overall incidence of all
      cause mortality was 31.5 per 100 person-years-at-risk (95%CI: 23.0-43.1).
      Conclusion: HIV-associated asymptomatic cryptococcosis is common in Cameroon,
      warranting integrated systematic screening and treatment. Biosynex CryptoPS holds
      promise, at point of care, for rapidly stratifying CrAg positive patients for
      optimal management including lumbar puncture and combination antifungal therapy
      when needed. Summary findings: Prevalence of CrAg and meningitis (CM) is high in
      Cameroon. Biosynex CryptoPS is comparable to IMMY LFA in CrAg screening. Its T2
      band correlates with high antigen titres and CM, thus promising for identifying
      patients requiring effective induction therapy. Note: This study was presented in
      part at the 10th International Conference on Cryptococcus and Cryptococcosis
      (ICCC) in Iguazu in Brazil from 26 to 30th March 2017 and won a prize oral
      presentation.

PMID- 29593673
TI  - Flavin-Based Electron Bifurcation, Ferredoxin, Flavodoxin, and Anaerobic
      Respiration With Protons (Ech) or NAD+ (Rnf) as Electron Acceptors: A Historical
      Review.
AB  - Flavin-based electron bifurcation is a newly discovered mechanism, by which a
      hydride electron pair from NAD(P)H, coenzyme F420H2, H2, or formate is split by
      flavoproteins into one-electron with a more negative reduction potential and one
      with a more positive reduction potential than that of the electron pair. Via this
      mechanism microorganisms generate low- potential electrons for the reduction of
      ferredoxins (Fd) and flavodoxins (Fld). The first example was described in 2008
      when it was found that the butyryl-CoA dehydrogenase-electron-transferring
      flavoprotein complex (Bcd-EtfAB) of Clostridium kluyveri couples the endergonic
      reduction of ferredoxin (E0' = -420 mV) with NADH (-320 mV) to the exergonic
      reduction of crotonyl-CoA to butyryl-CoA (-10 mV) with NADH. The discovery was
      followed by the finding of an electron-bifurcating Fd- and NAD-dependent [FeFe]
      hydrogenase (HydABC) in Thermotoga maritima (2009), Fd-dependent transhydrogenase
      (NfnAB) in various bacteria and archaea (2010), Fd- and H2-dependent
      heterodisulfide reductase (MvhADG-HdrABC) in methanogenic archaea (2011), Fd- and
      NADH-dependent caffeyl-CoA reductase (CarCDE) in Acetobacterium woodii (2013), Fd
      and NAD-dependent formate dehydrogenase (HylABC-FdhF2) in Clostridium acidi
      urici (2013), Fd- and NADP-dependent [FeFe]-hydrogenase (HytA-E) in Clostridium
      autoethanogrenum (2013), Fd(?)- and NADH-dependent methylene-tetrahydrofolate
      reductase (MetFV-HdrABC-MvhD) in Moorella thermoacetica (2014), Fd- and NAD
      dependent lactate dehydrogenase (LctBCD) in A. woodii (2015), Fd- and F420H2
      dependent heterodisulfide reductase (HdrA2B2C2) in Methanosarcina acetivorans
      (2017), and Fd- and NADH-dependent ubiquinol reductase (FixABCX) in Azotobacter
      vinelandii (2017). The electron-bifurcating flavoprotein complexes known to date
      fall into four groups that have evolved independently, namely those containing
      EtfAB (CarED, LctCB, FixBA) with bound FAD, a NuoF homolog (HydB, HytB, or HylB)
      harboring FMN, NfnB with bound FAD, or HdrA harboring FAD. All these
      flavoproteins are cytoplasmic except for the membrane-associated protein FixABCX.
      The organisms-in which they have been found-are strictly anaerobic microorganisms
      except for the aerobe A. vinelandii. The electron-bifurcating complexes are
      involved in a variety of processes such as butyric acid fermentation,
      methanogenesis, acetogenesis, anaerobic lactate oxidation, dissimilatory sulfate
      reduction, anaerobic- dearomatization, nitrogen fixation, and CO2 fixation. They
      contribute to energy conservation via the energy-converting ferredoxin: NAD+
      reductase complex Rnf or the energy-converting ferredoxin-dependent hydrogenase
      complex Ech. This Review describes how this mechanism was discovered.

PMID- 29593676
TI  - Prospects of Nanostructure Materials and Their Composites as Antimicrobial
      Agents.
AB  - Nanostructured materials (NSMs) have increasingly been used as a substitute for
      antibiotics and additives in various products to impart microbicidal effect. In
      particular, use of silver nanoparticles (AgNPs) has garnered huge researchers'
      attention as potent bactericidal agent due to the inherent antimicrobial property
      of the silver metal. Moreover, other nanomaterials (carbon nanotubes, fullerenes,
      graphene, chitosan, etc.) have also been studied for their antimicrobial effects
      in order ensure their application in widespread domains. The present review
      exclusively emphasizes on materials that possess antimicrobial activity in
      nanoscale range and describes their various modes of antimicrobial action. It
      also entails broad classification of NSMs along with their application in various
      fields. For instance, use of AgNPs in consumer products, gold nanoparticles
      (AuNPs) in drug delivery. Likewise, use of zinc oxide nanoparticles (ZnO-NPs) and
      titanium dioxide nanoparticles (TiO2-NPs) as additives in consumer merchandises
      and nanoscale chitosan (NCH) in medical products and wastewater treatment.
      Furthermore, this review briefly discusses the current scenario of antimicrobial
      nanostructured materials (aNSMs), limitations of current research and their
      future prospects. To put various perceptive insights on the recent advancements
      of such antimicrobials, an extended table is incorporated, which describes effect
      of NSMs of different dimensions on test microorganisms along with their potential
      widespread applications.

PMID- 29593677
TI  - Close Link Between Harmful Cyanobacterial Dominance and Associated
      Bacterioplankton in a Tropical Eutrophic Reservoir.
AB  - Cyanobacteria tend to become the dominant phytoplankton component in eutrophic
      freshwater environments during warmer seasons. However, general observations of
      cyanobacterial adaptive advantages in these circumstances are insufficient to
      explain the prevalence of one species over another in a bloom period, which may
      be related to particular strategies and interactions with other components of the
      plankton community. In this study, we present an integrative view of a mixed
      cyanobacterial bloom occurring during a warm, rainy period in a tropical
      hydropower reservoir. We used high-throughput sequencing to follow temporal
      shifts in the dominance of cyanobacterial genera and shifts in the associated
      heterotrophic bacteria community. The bloom occurred during late spring-summer
      and included two distinct periods. The first period corresponded to Microcystis
      aeruginosa complex (MAC) dominance with a contribution from Dolichospermum
      circinale; this pattern coincided with high water retention time and low
      transparency. The second period corresponded to Cylindrospermopsis raciborskii
      and Synechococcus spp. dominance, and the reservoir presented lower water
      retention time and higher water transparency. The major bacterial phyla were
      primarily Cyanobacteria and Proteobacteria, followed by Actinobacteria,
      Bacteroidetes, Verrucomicrobia, and Planctomycetes. Temporal shifts in the
      dominance of cyanobacterial genera were not only associated with physical
      features of the water but also with shifts in the associated heterotrophic
      bacteria. The MAC bloom was associated with a high abundance of Bacteroidetes,
      particularly Cytophagales. In the second bloom period, Planctomycetes increased
      in relative abundance, five Planctomycetes OTUs were positively correlated with
      Synechococcus or C. raciborskii OTUs. Our results suggest specific interactions
      of the main cyanobacterial genera with certain groups of the heterotrophic
      bacterial community. Thus, considering biotic interactions may lead to a better
      understanding of the shifts in cyanobacterial dominance.

PMID- 29593678
TI  - Pangenomic Definition of Prokaryotic Species and the Phylogenetic Structure of
      Prochlorococcus spp.
AB  - The pangenome is the collection of all groups of orthologous genes (OGGs) from a
      set of genomes. We apply the pangenome analysis to propose a definition of
      prokaryotic species based on identification of lineage-specific gene sets. While
      being similar to the classical biological definition based on allele flow, it
      does not rely on DNA similarity levels and does not require analysis of
      homologous recombination. Hence this definition is relatively objective and
      independent of arbitrary thresholds. A systematic analysis of 110 accepted
      species with the largest numbers of sequenced strains yields results largely
      consistent with the existing nomenclature. However, it has revealed that abundant
      marine cyanobacteria Prochlorococcus marinus should be divided into two species.
      As a control we have confirmed the paraphyletic origin of Yersinia
      pseudotuberculosis (with embedded, monophyletic Y. pestis) and Burkholderia
      pseudomallei (with B. mallei). We also demonstrate that by our definition and in
      accordance with recent studies Escherichia coli and Shigella spp. are one
      species.

PMID- 29593679
TI  - Flavoring Production in Kamut(r), Quinoa and Wheat Doughs Fermented by
      Lactobacillus paracasei, Lactobacillus plantarum, and Lactobacillus brevis: A
      SPME-GC/MS Study.
AB  - This study identified the odor-active compounds and the qualitative
      characteristics of doughs from "ancient" grains flours fermented by lactic acid
      bacteria. For this purpose doughs made with quinoa and Kamut(r) flours have been
      produced and inoculated with strains belonging to the species Lactobacillus
      paracasei, Lactobacillus plantarum and Lactobacillus brevis and compared with
      fermented doughs made from 100% wheat flour. The quality of the doughs was
      determined by assessment of pH, total titratable acidity, lactic acid bacteria
      growth and flavor compounds. The results showed that lactic acid bacteria used
      were able to grow in the different substrates reaching more than 9.0 log CFU/g
      after 24 h fermentation, although the best microbial growth was recorded in the
      doughs made with quinoa flour fermented with Lactobacillus paracasei I1. Good
      acidification and heterogeneous aromatic profile were recognized in all the
      doughs even if the volatile composition mainly derived from microbial specie.
      Among all the used strains, mostly Lactobacillus paracasei I1 positively
      contributed to the aromatic profile of the doughs, independently from flour type,
      producing the highest amount of different ketones such as, diacetyl, acetoin, 2,6
      dimethyl-4-heptanone, 5-methyl-3-hexanone, 4-methyl-3-penten-2-one, volatile
      compounds highly appreciated in the bakery products for their buttery, fatty and
      fruity notes. So, the positive characteristic of Lactobacillus paracasei I1 to
      enhance the production of desired volatile compounds could make it suitable as
      adjunct culture starter in the bakery industry. Many differences in volatile
      organic compounds derived also by the type of flour used. Quinoa fermented doughs
      were characterized for specific nutty, roasted, acid and buttery tones derived
      from pyrazines, ketones and acid compounds whereas Kamut(r) fermented doughs were
      characterized for fruity, rose, green and sweet tones derived from aldehydes and
      ketones production. So, the use of quinoa and Kamut(r) flours opportunely
      fermented, as partial or complete substitution of wheat flour, may be interesting
      for producing more balanced bakery products with respect to nutritional aspects
      and to unique aromatic profile. Furthermore, the supplementation of these flours,
      rich in protein content and free amino acids, could represent an optimal
      substrate to enhance the growth of lactic acid bacteria used as starter culture
      in leavened bakery products.

PMID- 29593680
TI  - Diversity and Contributions to Nitrogen Cycling and Carbon Fixation of Soil
      Salinity Shaped Microbial Communities in Tarim Basin.
AB  - Arid and semi-arid regions comprise nearly one-fifth of the earth's terrestrial
      surface. However, the diversities and functions of their soil microbial
      communities are not well understood, despite microbial ecological importance in
      driving biogeochemical cycling. Here, we analyzed the geochemistry and microbial
      communities of the desert soils from Tarim Basin, northwestern China. Our
      geochemical data indicated half of these soils are saline. Metagenomic analysis
      showed that bacterial phylotypes (89.72% on average) dominated the community,
      with relatively small proportions of Archaea (7.36%) and Eukaryota (2.21%).
      Proteobacteria, Firmicutes, Actinobacteria, and Euryarchaeota were most abundant
      based on metagenomic data, whereas genes attributed to Proteobacteria,
      Actinobacteria, Euryarchaeota, and Thaumarchaeota most actively transcribed. The
      most abundant phylotypes (Halobacterium, Halomonas, Burkholderia, Lactococcus,
      Clavibacter, Cellulomonas, Actinomycetospora, Beutenbergia, Pseudomonas, and
      Marinobacter) in each soil sample, based on metagenomic data, contributed
      marginally to the population of all microbial communities, whereas the putative
      halophiles, which contributed the most abundant transcripts, were in the majority
      of the active microbial population and is consistent with the soil salinity.
      Sample correlation analyses according to the detected and active genotypes showed
      significant differences, indicating high diversity of microbial communities among
      the Tarim soil samples. Regarding ecological functions based on the
      metatranscriptomic data, transcription of genes involved in various steps of
      nitrogen cycling, as well as carbon fixation, were observed in the tested soil
      samples. Metatranscriptomic data also indicated that Thaumarchaeota are crucial
      for ammonia oxidation and Proteobacteria play the most important role in other
      steps of nitrogen cycle. The reductive TCA pathway and dicarboxylate
      hydroxybutyrate cycle attributed to Proteobacteria and Crenarchaeota,
      respectively, were highly represented in carbon fixation. Our study reveals that
      the microbial communities could provide carbon and nitrogen nutrients for higher
      plants in the sandy saline soils of Tarim Basin.

PMID- 29593682
TI  - Root-Associated Fungi Shared Between Arbuscular Mycorrhizal and Ectomycorrhizal
      Conifers in a Temperate Forest.
AB  - Arbuscular mycorrhizal and ectomycorrhizal symbioses are among the most important
      drivers of terrestrial ecosystem dynamics. Historically, the two types of
      symbioses have been investigated separately because arbuscular mycorrhizal and
      ectomycorrhizal plant species are considered to host discrete sets of fungal
      symbionts (i.e., arbuscular mycorrhizal and ectomycorrhizal fungi, respectively).
      Nonetheless, recent studies based on high-throughput DNA sequencing technologies
      have suggested that diverse non-mycorrhizal fungi (e.g., endophytic fungi) with
      broad host ranges play roles in relationships between arbuscular mycorrhizal and
      ectomycorrhizal plant species in forest ecosystems. By analyzing an Illumina
      sequencing dataset of root-associated fungi in a temperate forest in Japan, we
      statistically examined whether co-occurring arbuscular mycorrhizal (Chamaecyparis
      obtusa) and ectomycorrhizal (Pinus densiflora) plant species could share non
      mycorrhizal fungal communities. Among the 919 fungal operational taxonomic units
      (OTUs) detected, OTUs in various taxonomic lineages were statistically designated
      as "generalists," which associated commonly with both coniferous species. The
      list of the generalists included fungi in the genera Meliniomyces, Oidiodendron,
      Cladophialophora, Rhizodermea, Penicillium, and Mortierella. Meanwhile, our
      statistical analysis also detected fungi preferentially associated with
      Chamaecyparis (e.g., Pezicula) or Pinus (e.g., Neolecta). Overall, this study
      provides a basis for future studies on how arbuscular mycorrhizal and
      ectomycorrhizal plant species interactively drive community- or ecosystem-scale
      processes. The physiological functions of the fungi highlighted in our host
      preference analysis deserve intensive investigations for understanding their
      roles in plant endosphere and rhizosphere.

PMID- 29593683
TI  - Commentary: Zika Virus in the Americas-Yet Another Arbovirus Threat.

PMID- 29593681
TI  - Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases.
AB  - The human body is colonized by millions of microorganisms named microbiota that
      interact with our tissues in a cooperative and non-pathogenic manner. These
      microorganisms are present in the skin, gut, nasal, oral cavities, and genital
      tract. In fact, it has been described that the microbiota contributes to
      balancing the immune system to maintain host homeostasis. The gut is a vital
      organ where microbiota can influence and determine the function of cells of the
      immune system and contributes to preserve the wellbeing of the individual.
      Several articles have emphasized the connection between intestinal autoimmune
      diseases, such as Crohn's disease with dysbiosis or an imbalance in the
      microbiota composition in the gut. However, little is known about the role of the
      microbiota in autoimmune pathologies affecting other tissues than the intestine.
      This article focuses on what is known about the role that gut microbiota can play
      in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's
      diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus,
      psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss
      as to how metabolites derived from bacteria could be used as potential therapies
      for non-intestinal autoimmune diseases.

PMID- 29593685
TI  - The Use of a Chimeric Rhodopsin Vector for the Detection of New Proteorhodopsins
      Based on Color.
AB  - Student microbial ecology laboratory courses are often conducted as condensed
      courses in which theory and wet lab work are combined in a very intensive short
      time period. In last decades, the study of marine microbial ecology is
      increasingly reliant on molecular-based methods, and as a result many of the
      research projects conducted in such courses require sequencing that is often not
      available on site and may take more time than a typical course allows. In this
      work, we describe a protocol combining molecular and functional methods for
      analyzing proteorhodopsins (PRs), with visible results in only 4-5 days that do
      not rely on sequencing. PRs were discovered in oceanic surface waters two decades
      ago, and have since been observed in different marine environments and diverse
      taxa, including the abundant alphaproteobacterial SAR11 group. PR subgroups are
      currently known to absorb green and blue light, and their distribution was
      previously explained by prevailing light conditions - green pigments at the
      surface and blue pigments in deeper waters, as blue light travels deeper in the
      water column. To detect PR in environmental samples, we created a chimeric
      plasmid suitable for direct expression of PRs using PCR amplification and
      functional analysis in Escherichia coli cells. Using this assay, we discovered
      several exceptional cases of PRs whose phenotypes differed from those predicted
      based on sequence only, including a previously undescribed yellow-light absorbing
      PRs. We applied this assay in two 10-days marine microbiology courses and found
      it to greatly enhance students' laboratory experience, enabling them to gain
      rapid visual feedback and colorful reward for their work. Furthermore we expect
      this assay to promote the use of functional assays for the discovery of new
      rhodopsin variants.

PMID- 29593684
TI  - Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology.
AB  - Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of
      serious neonatal infections. GBS is an opportunistic commensal constituting a
      part of the intestinal and vaginal physiologic flora and maternal colonization is
      the principal route of GBS transmission. GBS is a pathobiont that converts from
      the asymptomatic mucosal carriage state to a major bacterial pathogen causing
      severe invasive infections. At present, as many as 10 serotypes (Ia, Ib, and II
      IX) are recognized. The aim of the current review is to shed new light on the
      latest epidemiological data and clonal distribution of GBS in addition to
      discussing the most important colonization determinants at a molecular level. The
      distribution and predominance of certain serotypes is susceptible to variations
      and can change over time. With the availability of multilocus sequence typing
      scheme (MLST) data, it became clear that GBS strains of certain clonal complexes
      possess a higher potential to cause invasive disease, while other harbor mainly
      colonizing strains. Colonization and persistence in different host niches is
      dependent on the adherence capacity of GBS to host cells and tissues. Bacterial
      biofilms represent well-known virulence factors with a vital role in persistence
      and chronic infections. In addition, GBS colonization, persistence,
      translocation, and invasion of host barriers are largely dependent on their
      adherence abilities to host cells and extracellular matrix proteins (ECM). Major
      adhesins mediating GBS interaction with host cells include the fibrinogen-binding
      proteins (Fbs), the laminin-binding protein (Lmb), the group B streptococcal C5a
      peptidase (ScpB), the streptococcal fibronectin binding protein A (SfbA), the GBS
      immunogenic bacterial adhesin (BibA), and the hypervirulent adhesin (HvgA). These
      adhesins facilitate persistent and intimate contacts between the bacterial cell
      and the host, while global virulence regulators play a major role in the
      transition to invasive infections. This review combines for first time
      epidemiological data with data on adherence and colonization for GBS.
      Investigating the epidemiology along with understanding the determinants of
      mucosal colonization and the development of invasive disease at a molecular level
      is therefore important for the development of strategies to prevent invasive GBS
      disease worldwide.

PMID- 29593686
TI  - Skin Microbiomes of California Terrestrial Salamanders Are Influenced by Habitat
      More Than Host Phylogeny.
AB  - A multitude of microorganisms live on and within plant and animal hosts, yet the
      ecology and evolution of these microbial communities remains poorly understood in
      many taxa. This study examined the extent to which environmental factors and host
      taxonomic identity explain microbiome variation within two salamander genera,
      Ensatina and Batrachoseps, in the family Plethodontidae. In particular, we
      assessed whether microbiome differentiation paralleled host genetic distance at
      three levels of taxonomy: genus and high and low clade levels within Ensatina
      eschscholtzii. We predicted that more genetically related host populations would
      have more similar microbiomes than more distantly related host populations. We
      found that salamander microbiomes possess bacterial species that are most likely
      acquired from their surrounding soil environment, but the relative representation
      of those bacterial species is significantly different on the skin of salamanders
      compared to soil. We found differences in skin microbiome alpha diversity among
      Ensatina higher and lower clade groups, as well as differences between Ensatina
      and Batrachoseps. We also found that relative microbiome composition (beta
      diversity) did vary between Ensatina lower clades, but differences were driven by
      only a few clades and not correlated to clade genetic distances. We conclude this
      difference was likely a result of Ensatina lower clades being associated with
      geographic location and habitat type, as salamander identity at higher taxonomic
      levels (genus and Ensatina higher clades) was a weak predictor of microbiome
      composition. These results lead us to conclude that environmental factors are
      likely playing a more significant role in salamander cutaneous microbiome
      assemblages than host-specific traits.

PMID- 29593687
TI  - Carrying Capacity and Colonization Dynamics of Curvibacter in the Hydra Host
      Habitat.
AB  - Most eukaryotic species are colonized by a microbial community - the microbiota -
      that is acquired during early life stages and is critical to host development and
      health. Much research has focused on the microbiota biodiversity during the host
      life, however, empirical data on the basic ecological principles that govern
      microbiota assembly is lacking. Here we quantify the contribution of colonizer
      order, arrival time and colonization history to microbiota assembly on a host. We
      established the freshwater polyp Hydra vulgaris and its dominant colonizer
      Curvibacter as a model system that enables the visualization and quantification
      of colonizer population size at the single cell resolution, in vivo, in real
      time. We estimate the carrying capacity of a single Hydra polyp as 2 *
      105Curvibacter cells, which is robust among individuals and time. Colonization
      experiments reveal a clear priority effect of first colonizers that depends on
      arrival time and colonization history. First arriving colonizers achieve a
      numerical advantage over secondary colonizers within a short time lag of 24 h.
      Furthermore, colonizers primed for the Hydra habitat achieve a numerical
      advantage in the absence of a time lag. These results follow the theoretical
      expectations for any bacterial habitat with a finite carrying capacity. Thus,
      Hydra colonization and succession processes are largely determined by the habitat
      occupancy over time and Curvibacter colonization history. Our experiments provide
      empirical data on the basic steps of host-associated microbiota establishment -
      the colonization stage. The presented approach supplies a framework for studying
      habitat characteristics and colonization dynamics within the host-microbe
      setting.

PMID- 29593688
TI  - A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage
      Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of
      Pulmonary Tuberculosis in China: A Two-Center Prospective Study.
AB  - Introduction: The Xpert MTB/RIF is recommended by the World Health Organization
      as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB);
      however, China does not routinely use this test, partially due to the lack of a
      sufficient number of systematic evaluations of this assay in local patients. The
      aims of this study were to comprehensively assess the diagnostic performance of
      Xpert MTB/RIF, either alone or in combination with conventional assays for the
      diagnosis of pulmonary TB in adult Chinese patients. Methods: Xpert MTB/RIF tests
      were performed in 190 adult patients with suspected pulmonary TB, using
      bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional
      tests were carried out using the same BALF samples. Using two different reference
      standards, the performance of Xpert MTB/RIF, conventional assays and their
      combinations were evaluated. Results: Using mycobacterial culture as the
      reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy
      in detecting Mycobacterium tuberculosis. When final diagnosis, based on clinical
      criteria, was employed as the reference standard, Xpert MTB/RIF showed an even
      higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of
      96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify
      pulmonary TB cases undetected by culture or smear-microscopy. Combining smear
      microscopy and Xpert MTB/RIF was found to be the most accurate early predictor
      for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly
      deviated from that by phenotypic antibiotic susceptibility testing and requires
      further study with a larger sample size. Conclusion: This two-center prospective
      study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB
      in adult Chinese patients. These findings might contribute to the optimization of
      current diagnostic algorithms for pulmonary TB in China.

PMID- 29593689
TI  - Comparative mRNA-Seq Analysis Reveals the Improved EPS Production Machinery in
      Streptococcus thermophilus ASCC 1275 During Optimized Milk Fermentation.
AB  - Exo-polysaccharide (EPS) produced by dairy starters plays critical roles in
      improving texture and functionalities of fermented dairy products. One of such
      high EPS producers, Streptococcus thermophilus ASCC 1275 (ST1275) was used as a
      model dairy strain to understand the stimulation of its EPS production under
      optimal milk fermentation conditions. The mRNA-seq analysis and targeted pathway
      analysis indicate that genes associated with lactose (milk sugar) catabolism, EPS
      assembly, proteolytic activity, and arginine/methionine/cysteine synthesis and
      transport in ST1275 were significantly up-regulated under the optimized
      conditions of pH 5.5, 40 degrees C, or WPI supplementation compared to that of pH
      6.5 and 37 degrees C, respectively. This indicates that genes involved in above
      metabolisms cooperate together for improving EPS yield from ST1275. This study
      provides a global view map on potential targeted pathways and specific genes
      accounted for enhanced EPS production in Str. thermophilus and that could be
      modulated by fermentation conditions.

PMID- 29593690
TI  - A Validation Approach of an End-to-End Whole Genome Sequencing Workflow for
      Source Tracking of Listeria monocytogenes and Salmonella enterica.
AB  - Whole genome sequencing (WGS), using high throughput sequencing technology,
      reveals the complete sequence of the bacterial genome in a few days. WGS is
      increasingly being used for source tracking, pathogen surveillance and outbreak
      investigation due to its high discriminatory power. In the food industry, WGS
      used for source tracking is beneficial to support contamination investigations.
      Despite its increased use, no standards or guidelines are available today for the
      use of WGS in outbreak and/or trace-back investigations. Here we present a
      validation of our complete (end-to-end) WGS workflow for Listeria monocytogenes
      and Salmonella enterica including: subculture of isolates, DNA extraction,
      sequencing and bioinformatics analysis. This end-to-end WGS workflow was
      evaluated according to the following performance criteria: stability,
      repeatability, reproducibility, discriminatory power, and epidemiological
      concordance. The current study showed that few single nucleotide polymorphism
      (SNPs) were observed for L. monocytogenes and S. enterica when comparing genome
      sequences from five independent colonies from the first subculture and five
      independent colonies after the tenth subculture. Consequently, the stability of
      the WGS workflow for L. monocytogenes and S. enterica was demonstrated despite
      the few genomic variations that can occur during subculturing steps.
      Repeatability and reproducibility were also demonstrated. The WGS workflow was
      shown to have a high discriminatory power and has the ability to show genetic
      relatedness. Additionally, the WGS workflow was able to reproduce published
      outbreak investigation results, illustrating its capability of showing
      epidemiological concordance. The current study proposes a validation approach
      comprising all steps of a WGS workflow and demonstrates that the workflow can be
      applied to L. monocytogenes or S. enterica.

PMID- 29593691
TI  - Isolation, Identification, Prevalence, and Genetic Diversity of Bacillus cereus
      Group Bacteria From Different Foodstuffs in Tunisia.
AB  - Bacillus cereus group is widespread in nature and foods. Several members of this
      group are recognized as causing food spoilage and/or health issues. This study
      was designed to determine the prevalence and genetic diversity of the B. cereus
      group strains isolated in Tunisia from different foods (cereals, spices, cooked
      food, fresh-cut vegetables, raw and cooked poultry meats, seafood, canned,
      pastry, and dairy products). In total, 687 different samples were collected and
      searched for the presence of the B. cereus group after selective plating on MYP
      agar and enumeration of each sample. The typical pink-orange uniform colonies
      surrounded by a zone of precipitate were assumed to belong to the B. cereus
      group. One typical colony from each sample was subcultured and preserved as
      cryoculture. Overall, 191 (27.8%) food samples were found positive, giving rise
      to a collection of 191 B. cereus-like isolates. The concentration of B. cereus
      like bacteria were below 103 cfu/g or ml in 77.5% of the tested samples. Higher
      counts (>104 cfu/g or ml) were found in 6.8% of samples including fresh-cut
      vegetables, cooked foods, cereals, and pastry products. To verify whether B.
      cereus-like isolates belonged to the B. cereus group, a PCR test targeting the
      sspE gene sequence specific of the group was carried out. Therefore, 174 isolates
      were found to be positive. Food samples were contaminated as follows: cereals
      (67.6%), pastry products (46.2%), cooked food (40.8%), cooked poultry meat
      (32.7%), seafood products (32.3%), spices (28.8%), canned products (16.7%), raw
      poultry meat (9.4%), fresh-cut vegetables (5.0%), and dairy products (4.8%). The
      174 B. cereus isolates were characterized by partial sequencing of the panC gene,
      using a Sym'Previous software tool to assign them to different phylogenetic
      groups. Strains were distributed as follows: 61.3, 29.5, 7.5, and 1.7% in the
      group III, IV, II, and V, respectively. The genetic diversity was further
      assessed by ERIC-PCR and PFGE typing methods. PFGE and ERIC-PCR patterns analysis
      allowed discriminating 143 and 99 different profiles, respectivey. These
      findings, associated to a relatively higher prevalence of B. cereus group in
      different foods, could be a significant etiological agent of food in Tunisia.

PMID- 29593692
TI  - Optimized Co-extraction and Quantification of DNA From Enteric Pathogens in
      Surface Water Samples Near Produce Fields in California.
AB  - Pathogen contamination of surface water is a health hazard in agricultural
      environments primarily due to the potential for contamination of crops.
      Furthermore, pathogen levels in surface water are often unreported or under
      reported due to difficulty with culture of the bacteria. The pathogens are often
      present, but require resuscitation, making quantification difficult. Frequently,
      this leads to the use of quantitative PCR targeted to genes unique to the
      pathogens. However, multiple pathogen types are commonly in the same water
      sample, both gram + and gram -, leading to problems with DNA extraction. With
      Shiga toxin-producing Escherichia coli (STEC), Salmonella enterica and Listeria
      monocytogenes as target, a method was optimized to co-extract all three and
      quantify the level of each using droplet digital PCR (ddPCR). Multiplexed target
      genes in STEC were virulence genes, shiga toxin 2 (stx2) and hemolysin (ehx).
      Likewise, multiplexed targets in Listeria and Salmonella were the virulence genes
      listeriolysin (hly) and invasion protein A (invA). Water samples were processed
      using microbiological techniques for each of the pathogens and duplicate water
      samples were quantified by ddPCR. A significant correlation was found between
      culture and ddPCR results indicating detection primarily of culturable cells by
      ddPCR. Average virulence gene levels were 923, 23 k, 69 and 152 copies per sample
      for stx2, ehx, hly and invA, respectively. Additionally, stx2, ehx and inv levels
      were significantly correlated (P < 0.05, R = 0.34) with generic E. coli MPN
      levels in the duplicate samples. Indirect quantification with ddPCR will improve
      understanding of prevalence of the pathogens and may reduce risks associated with
      contaminated surface water.

PMID- 29593693
TI  - Identification of Four Distinct Phylogenetic Groups in Flavobacterium columnare
      With Fish Host Associations.
AB  - Columnaris disease, caused by the Gram-negative bacterium Flavobacterium
      columnare, is one of the most prevalent fish diseases worldwide. An exceptionally
      high level of genetic diversity among isolates of F. columnare has long been
      recognized, whereby six established genomovars have been described to date.
      However, little has been done to quantify or characterize this diversity further
      in a systematic fashion. The objective of this research was to perform
      phylogenetic analyses of 16S rRNA and housekeeping gene sequences to decipher the
      genetic diversity of F. columnare. Fifty isolates and/or genomes of F. columnare,
      originating from diverse years, geographic locations, fish hosts, and
      representative of the six genomovars were analyzed in this study. A multilocus
      phylogenetic analysis (MLPA) of the 16S rRNA and six housekeeping genes supported
      four distinct F. columnare genetic groups. There were associations between
      genomovar and genetic group, but these relationships were imperfect indicating
      that genomovar assignment does not accurately reflect F. columnare genetic
      diversity. To expand the dataset, an additional 90 16S rRNA gene sequences were
      retrieved from GenBank and a phylogenetic analysis of this larger dataset also
      supported the establishment of four genetic groups. Examination of isolate
      historical data indicated biological relevance to the identified genetic
      diversity, with some genetic groups isolated preferentially from specific fish
      species or families. It is proposed that F. columnare isolates be assigned to the
      four genetic groups defined in this study rather than genomovar in order to
      facilitate a standard nomenclature across the scientific community. An increased
      understanding of which genetic groups are most prevalent in different regions
      and/or aquaculture industries may allow for the development of improved targeted
      control and treatment measures for columnaris disease.

PMID- 29593694
TI  - Amino Acid Substitutions HA A150V, PA A343T, and PB2 E627K Increase the Virulence
      of H5N6 Influenza Virus in Mice.
AB  - H5N6 avian influenza viruses (AIVs) can cause severe pneumonia and death in
      humans. However, the molecular determinants of H5N6 influenza virus mammalian
      adaption are still unclear. Three amino acid substitutions (HA A150V, PA A343T,
      PB2 E627K) are observed in H5N6 virus A/duck/Zhejiang/6D2/2013 (6D2) in lung-to
      lung passage in mice. These substitutions are crucial to the pathogenicity of
      mouse-adapted virus. In this study, we investigated the contribution of each
      amino acid substitution in the virus by reverse genetics. The results demonstrate
      that HA A150V greatly altered the receptor binding preference of 6D2. Virus
      bearing this substitution acquired increased mortality than mice infected with
      wild-type 6D2. The PA A343T substitution mildly enhanced viral polymerase
      activity but the reduced survival rate in mice indicates this substitution may
      change the immunoreaction of the host. The well-known PB2 E627K substitution
      increased eight folds the relative polymerase activity compared to PA A343T and
      resulted in 100% death rate in mice. In addition, we show that PA A343T
      dramatically exacerbates the effect of PB2 E627K on viral polymerase activity;
      when combined, these two substitutions work synergistically. However, HA A150V
      and PA A343T seemed to attenuate PB2 E627K in vivo, which implies the difference
      between mixed viral populations under natural condition and single population
      under experiment, specialization and cooperation in quasispecies is important in
      the process of adaption. This study suggests that HA A150V, PA A343T, and PB2
      E627K are crucial in the adaption and increased pathogenicity of H5N6 in
      mammalian hosts.

PMID- 29593695
TI  - Research on Volatile Organic Compounds From Bacillus subtilis CF-3: Biocontrol
      Effects on Fruit Fungal Pathogens and Dynamic Changes During Fermentation.
AB  - The dynamic changes of the levels of volatile organic compounds (VOCs) produced
      by Bacillus subtilis CF-3 and their biocontrol effects on common fungal pathogens
      were researched in this study. The results showed that the VOCs in 24-h
      fermentation liquid (24hFL) of B. subtilis CF-3 inhibited mycelial growth of
      Botrytis cinerea, Colletotrichum gloeosporioides, Penicillium expansum, Monilinia
      fructicola, and Alternaria alternata, with a mean inhibition rate of 59.97%. The
      inhibitory effect on M. fructicola and C. gloeosporioides was the highest; they
      were therefore selected as target fungal pathogens for further experiments. Based
      on headspace solid-phase microextraction combined with gas chromatography-mass
      spectrometry (HS-SPME-GC-MS), 74 potential VOCs were identified during the
      fermentation: 15 alcohols, 18 ketones, 4 pyrazines, 4 esters, 10 acids, 5
      phenols, 3 hydrocarbons, 3 amines, 2 aldehydes, 5 ethers, and 5 other components.
      At different fermentation times, the type and content of VOCs were different.
      Most of the potential VOCs (62 VOCs) were identified in the 48hFL. The inhibition
      rates of all VOCs reached their peaks (73.46% on M. fructicola and 63.63% on C.
      gloeosporioides) in the 24hFL. Among the identified VOCs, 2,4-di-tert
      butylphenol, 1-octanol, and benzothiazole showed significant positive
      correlations with the rates of M. fructicola and C. gloeosporioides inhibition.
      Benzoic acid and benzaldehyde showed a significant positive correlation with the
      rates of M. fructicola inhibition, and anisole and 3-methylbutanal showed a
      significant positive correlation with the rates of C. gloeosporioides inhibition.
      In vitro, 2,4-di-tert-butylphenol showed a strong inhibitory effect on both M.
      fructicola and C. gloeosporioides. In vivo, benzothiazole showed the strongest
      inhibitory effect on the mycelial extensions of both M. fructicola and C.
      gloeosporioides, which also led to an increased rate of healthy fruit. The
      results of the present study clarified that 2,4-di-tert-butylthiophenol and
      benzothiazole are key inhibitory VOCs produced by B. subtilis CF-3.

PMID- 29593696
TI  - Transmission of Turnip yellows virus by Myzus persicae Is Reduced by Feeding
      Aphids on Double-Stranded RNA Targeting the Ephrin Receptor Protein.
AB  - Aphid-transmitted plant viruses are a threat for major crops causing massive
      economic loss worldwide. Members in the Luteoviridae family are transmitted by
      aphids in a circulative and non-replicative mode. Virions are acquired by aphids
      when ingesting sap from infected plants and are transported through the gut and
      the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on
      virus-specific receptors largely unknown. Once released into the salivary canal,
      virions are inoculated to plants, together with saliva, during a subsequent
      feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin
      receptor (Eph) is a novel aphid protein involved in the transmission of the
      Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus
      persicae. The minor capsid protein of TuYV, essential for aphid transmission, was
      able to bind the external domain of Eph in yeast. Feeding M. persicae on in
      planta- or in vitro-synthesized dsRNA targeting Eph-mRNA (dsRNAEph) did not
      affect aphid feeding behavior but reduced accumulation of TuYV genomes in the
      aphid's body. Consequently, TuYV transmission efficiency by the dsRNAEph-treated
      aphids was reproducibly inhibited and we brought evidence that Eph is likely
      involved in intestinal uptake of the virion. The inhibition of virus uptake after
      dsRNAEph acquisition was also observed for two other poleroviruses transmitted by
      M. persicae, suggesting a broader role of Eph in polerovirus transmission.
      Finally, dsRNAEph acquisition by aphids did not affect nymph production. These
      results pave the way toward an ecologically safe alternative of insecticide
      treatments that are used to lower aphid populations and reduce polerovirus
      damages.

PMID- 29593698
TI  - Widespread Elevational Occurrence of Antifungal Bacteria in Andean Amphibians
      Decimated by Disease: A Complex Role for Skin Symbionts in Defense Against
      Chytridiomycosis.
AB  - Emerging infectious disease is a growing threat to global health, and recent
      discoveries reveal that the microbiota dwelling on and within hosts can play an
      important role in health and disease. To understand the capacity of skin bacteria
      to protect amphibian hosts from the fungal disease chytridiomycosis caused by
      Batrachochytrium dendrobatidis (Bd), we isolated 192 bacterial morphotypes from
      the skin of 28 host species of frogs (families Bufonidae, Centrolenidae,
      Hemiphractidae, Hylidae, Leptodactylidae, Strabomantidae, and Telmatobiidae)
      collected from the eastern slopes of the Peruvian Andes (540-3,865 m a.s.l.) in
      the Kosnipata Valley near Manu National Park, a site where we previously
      documented the collapse of montane frog communities following chytridiomycosis
      epizootics. We obtained isolates through agar culture from skin swabs of wild
      frogs, and identified bacterial isolates by comparing 16S rRNA sequences against
      the GenBank database using BLAST. We identified 178 bacterial strains of 38
      genera, including 59 bacterial species not previously reported from any amphibian
      host. The most common bacterial isolates were species of Pseudomonas,
      Paenibacillus, Chryseobacterium, Comamonas, Sphingobacterium, and
      Stenotrophomonas. We assayed the anti-fungal abilities of 133 bacterial isolates
      from 26 frog species. To test whether cutaneous bacteria might inhibit growth of
      the fungal pathogen, we used a local Bd strain isolated from the mouthparts of
      stream-dwelling tadpoles (Hypsiboas gladiator, Hylidae). We quantified Bd
      inhibition in vitro with co-culture assays. We found 20 bacterial isolates that
      inhibited Bd growth, including three isolates not previously known for such
      inhibitory abilities. Anti-Bd isolates occurred on aquatic and terrestrial
      breeding frogs across a wide range of elevations (560-3,695 m a.s.l.). The
      inhibitory ability of anti-Bd isolates varied considerably. The proportion of
      anti-Bd isolates was lowest at mid-elevations (6%), where amphibian declines have
      been steepest, and among hosts that are highly susceptible to chytridiomycosis (0
      14%). Among non-susceptible species, two had the highest proportion of anti-Bd
      isolates (40 and 45%), but one common and non-susceptible species had a low
      proportion (13%). In conclusion, we show that anti-Bd bacteria are widely
      distributed elevationally and phylogenetically across frog species that have
      persisted in a region where chytridiomycosis emerged, caused a devastating
      epizootic and continues to infect amphibians.

PMID- 29593699
TI  - Commentary: Fungal lifestyle reflected in serine protease repertoire.

PMID- 29593697
TI  - HERV Envelope Proteins: Physiological Role and Pathogenic Potential in Cancer and
      Autoimmunity.
AB  - Human endogenous retroviruses (HERVs) are relics of ancient infections accounting
      for about the 8% of our genome. Despite their persistence in human DNA led to the
      accumulation of mutations, HERVs are still contributing to the human
      transcriptome, and a growing number of findings suggests that their expression
      products may have a role in various diseases. Among HERV products, the envelope
      proteins (Env) are currently highly investigated for their pathogenic properties,
      which could likely be participating to several disorders with complex etiology,
      particularly in the contexts of autoimmunity and cancer. In fact, HERV Env
      proteins have been shown, on the one side, to trigger both innate and adaptive
      immunity, prompting inflammatory, cytotoxic and apoptotic reactions; and, on the
      other side, to prevent the immune response activation, presenting
      immunosuppressive properties and acting as immune downregulators. In addition,
      HERV Env proteins have been shown to induce abnormal cell-cell fusion, possibly
      contributing to tumor development and metastasizing processes. Remarkably, even
      highly defective HERV env genes and alternative env splicing variants can provide
      further mechanisms of pathogenesis. A well-known example is the HERV-K(HML2) env
      gene that, depending on the presence or the absence of a 292-bp deletion, can
      originate two proteins of different length (Np9 and Rec) proposed to have
      oncogenic properties. The understanding of their involvement in complex
      pathological disorders made HERV Env proteins potential targets for therapeutic
      interventions. Of note, a monoclonal antibody directed against a HERV-W Env is
      currently under clinical trial as therapeutic approach for multiple sclerosis,
      representing the first HERV-based treatment. The present review will focus on the
      current knowledge of the HERV Env expression, summarizing its role in human
      physiology and its possible pathogenic effects in various cancer and autoimmune
      disorders. It moreover analyzes HERV Env possible exploitation for the
      development of innovative therapeutic strategies.

PMID- 29593701
TI  - Metabolic Phenotype Characterization of Botrytis cinerea, the Causal Agent of
      Gray Mold.
AB  - Botrytis cinerea, which causes gray mold, is an important pathogen in four
      important economic crops, tomato, tobacco, cucumber and strawberry, in China and
      worldwide. Metabolic phenomics data on B. cinerea isolates from these four crops
      were characterized and compared for 950 phenotypes with a BIOLOG Phenotype
      MicroArray (PM). The results showed that the metabolic fingerprints of the four
      B. cinerea isolates were similar to each other with minimal differences. B.
      cinerea isolates all metabolized more than 17% of the tested carbon sources, 63%
      of the amino acid nitrogen substrates, 80% of the peptide nitrogen substrates,
      93% of the phosphorus substrates, and 97% of the sulfur substrates. Carbon
      substrates of organic acids and carbohydrates, and nitrogen substrates of amino
      acids and peptides were the significant utilization patterns for B. cinerea. Each
      B. cinerea isolate contained 94 biosynthetic pathways. These isolates showed a
      large range of adaptabilities and were still able to metabolize substrates in the
      presence of the osmolytes, including up to 6% potassium chloride, 10% sodium
      chloride, 5% sodium sulfate, 6% sodium formate, 20% ethylene glycol, and 3% urea.
      These isolates all showed active metabolism in environments with pH values from
      3.5 to 8.5 and exhibited decarboxylase activities. These characterizations
      provide a theoretical basis for the study of B. cinerea in biochemistry and
      metabolic phenomics and provide valuable clues to finding potential new ways to
      manage gray mold.

PMID- 29593700
TI  - Identification and Characterization of Wheat Yellow Striate Virus, a Novel
      Leafhopper-Transmitted Nucleorhabdovirus Infecting Wheat.
AB  - A new wheat viral disease was found in China. Bullet-shaped viral particles
      within the nucleus of the infected wheat leave cells, which possessed 180-210 nm
      length and 35-40 nm width, were observed under transmission electron microscopy.
      A putative wheat-infecting rhabdovirus vectored by the leafhopper Psammotettix
      alienus was identified and tentatively named wheat yellow striate virus (WYSV).
      The full-length nucleotide sequence of WYSV was determined using transcriptome
      sequencing and RACE analysis of both wheat samples and leafhoppers P. alienus.
      The negative-sense RNA genome of WYSV contains 14,486 nucleotides (nt) and seven
      open reading frames (ORFs) encode deduced proteins in the order N-P-P3-M-P6-G-L
      on the antisense strand. In addition, WYSV genome has a 76-nt 3' leader RNA and a
      258-nt 5' trailer, and the ORFs are separated by conserved intergenic sequences.
      The entire genome sequence shares 58.1 and 57.7% nucleotide sequence identity
      with two strains of rice yellow stunt virus (RYSV-A and RYSV-B) genomes,
      respectively. The highest amino acid sequence identity was 63.8% between the L
      proteins of the WYSV and RYSV-B, but the lowest was 29.5% between the P6 proteins
      of these viruses. Phylogenetic analysis firmly established WYSV as a new member
      of the genus Nucleorhabdovirus. Collectively, this study provided evidence that
      WYSV is likely the first nucleorhabdovirus described infecting wheat via
      leafhopper P. alienus transmission.

PMID- 29593702
TI  - Use of a Potential Probiotic, Lactobacillus plantarum L7, for the Preparation of
      a Rice-Based Fermented Beverage.
AB  - This study aimed to isolate potential probiotic lactic acid bacteria from a
      traditional rice-based fermented beverage "bhaati jaanr" and to evaluate their
      role during preparation of the beverage. Among various isolates, Lactobacillus
      plantarum strain L7 exhibited satisfactory in vitro probiotic characteristics
      such as acid resistance and bile tolerance, cell surface hydrophobicity, auto
      aggregation, antibiotic susceptibility, and antimicrobial activities. Therefore,
      performance of L7 as a starter culture in rice fermentation was determined during
      a 6-day rice fermentation study. L. plantarum L7 decreased the pH, associated
      with an increase in total titratable acidity and organic acid production up to
      the 4th day of fermentation. The highest concentrations of succinic acid (0.37
      mg/g), lactic acid (4.95 mg/g), and acetic acid (0.36 mg/g) were recorded on the
      3rd, 4th, and 5th days of fermentation, respectively. Saccharifying (148.13
      MUg/min g-1) and liquefying (89.47 MUg/min g-1) activities were the highest on
      days 3 and 2, respectively, and thereafter, they decreased. Phytase activity and
      the cleavage of free minerals (sodium, calcium, magnesium, manganese, and
      ferrous) increased up to days 3-4. The concentration of various accumulated malto
      oligosaccharides (glucose, fructose, maltotriose, and maltoterose) was noted to
      be the maximum on days 4 and 5. Furthermore, gas chromatography-mass spectrometry
      analysis indicated the presence of various volatile compounds. The fermented
      material also exhibited 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity. Therefore,
      the probiotic, L. plantarum L7, has a significant role in the fermentation of
      this beverage and enhances its functional properties.

PMID- 29593703
TI  - Response of Nitrifier and Denitrifier Abundance and Microbial Community Structure
      to Experimental Warming in an Agricultural Ecosystem.
AB  - Soil microbial community plays an important role in terrestrial carbon and
      nitrogen cycling. However, the response of the soil nitrifier and denitrifier
      communities to climate warming is poorly understood. A long-term field warming
      experiment has been conducted for 8 years at Luancheng Experimental Farm Station
      on the North China Plain; we used this field to examine how soil microbial
      community structure, nitrifier, and denitrifier abundance respond to warming
      under regular irrigation (RI) and high irrigation (HI) at different soil depths
      (0-5, 5-10, and 10-20 cm). Nitrifier, denitrifier, and the total bacterial
      abundance were assessed by quantitative polymerase chain reaction of the
      functional genes and 16S rRNA gene, respectively. Bacterial community structure
      was studied through high throughput sequencing of the 16S rRNA gene. Under RI,
      warming significantly (P < 0.05) increased the potential nitrification rate and
      nitrate concentration and decreased the soil moisture. In most of the samples,
      warming increased the ammonia-oxidizing bacteria abundance but decreased the
      ammonia-oxidizing archaea (AOA) and denitrifier (nirK, nirS, and nosZ genes)
      abundance. Under HI, there was a highly increased AOA and 16S rRNA gene abundance
      and a slightly higher denitrifier abundance compared with RI. Warming decreased
      the bacterial diversity and species richness, and the microbial community
      structure differed greatly between the warmed and control plots. The decrease in
      bacterial diversity was higher in RI than HI and at the 0-5 cm depths than at the
      5-10 and 10-20 cm soil depths. Warming led to an increase in the relative
      abundance of Actinobacteria, Bacteroidetes, and TM7 but a decrease in
      Acidobacteria, Alphaproteobacteria, Deltaproteobacteria, Nitrospira, and
      Planctomycetes. The greater shift in microbial community structure was observed
      only in RI at the 0-5 cm soil depth. This study provides new insight into our
      understanding of the nitrifier and denitrifier activity and microbial community
      response to climate warming in agricultural ecosystems.

PMID- 29593705
TI  - Commentary: A Novel and Validated Protocol for Performing MIC Tests to Determine
      the Susceptibility of Piscirickettsia salmonis Isolates to Florfenicol and
      Oxytetracycline.

PMID- 29593704
TI  - Cellular Injuries in Cronobacter sakazakii CIP 103183T and Salmonella enterica
      Exposed to Drying and Subsequent Heat Treatment in Milk Powder.
AB  - Because of the ability of foodborne pathogens to survive in low-moisture foods,
      their decontamination is an important issue in food protection. This study aimed
      to clarify some of the cellular mechanisms involved in inactivation of foodborne
      pathogens after drying and subsequent heating. Individual strains of Salmonella
      Typhimurium, Salmonella Senftenberg, and Cronobacter sakazakii were mixed into
      whole milk powder and dried to different water activity levels (0.25 and 0.58);
      the number of surviving cells was determined after drying and subsequent thermal
      treatments in closed vessels at 90 and 100 degrees C, for 30 and 120 s. For each
      condition, the percentage of unculturable cells was estimated and, in parallel,
      membrane permeability and respiratory activity were estimated by flow cytometry
      using fluorescent probes. After drying, it was clearly observable that the
      percentage of unculturable cells was correlated with the percentage of
      permeabilized cells (responsible for 20-40% of the total inactivated bacteria
      after drying), and to a lesser degree with the percentage of cells presenting
      with loss of respiratory activity. In contrast, the percentages of unculturable
      cells observed after heat treatment were strongly correlated with the loss of
      respiratory activity and weakly with membrane permeability (for 70-80% of the
      total inactivated bacteria after heat treatment). We conclude that cell
      inactivation during drying is closely linked to membrane permeabilization and
      that heat treatment of dried cells affects principally their respiratory
      activity. These results legitimize the use of time-temperature scales and allow
      better understanding of the cellular mechanisms of bacterial death during drying
      and subsequent heat treatment. These results may also allow better optimization
      of the decontamination process to ensure food safety by targeting the most
      deleterious conditions for bacterial cells without denaturing the food product.

PMID- 29593706
TI  - Regulation of Human Natural Killer Cell IFN-gamma Production by MicroRNA-146a via
      Targeting the NF-kappaB Signaling Pathway.
AB  - Natural killer (NK) cells are one group of innate lymphocytes that are important
      for host defense against malignancy and viruses. MicroRNAs (miRNAs) play a
      critical role in regulating responses of immune cells including NK cells.
      Accumulating evidence suggests that miR-146a is involved in the regulation of
      immune responses. However, the mechanism by which miR-146a regulates NK cell
      function is largely unknown. In the current study, we found that miR-146a
      intrinsically regulated NK cell function. Forced overexpression of miR-146a
      decreased IFN-gamma production, whereas downregulation of miR-146a by anti-miR
      146a significantly enhanced IFN-gamma production in the human NK-92 cell line and
      primary human NK cells upon stimulation with IL-12 or co-stimulation with IL-12
      and IL-18. Mechanistically, miR-146a regulated IFN-gamma production via NF
      kappaB, as evidenced in NK-92 cells, by downregulation of NF-kappaB p65
      phosphorylation when miR-146a was overexpressed but upregulation of NF-kappaB p65
      phosphorylation when anti-miR-146a was overexpressed. miR-146a directly targeted
      IRAK1 and TRAF6, the upstream signaling components of the NF-kappaB signaling
      pathway. This direct targeting mechanism confirmed the above gain- and loss-of
      function approaches. However, the potent IFN-gamma-producing subset, CD56bright
      NK cells, expressed higher levels of miR-146a than the lesser IFN-gamma-producing
      subset, CD56dim NK cells. We also observed that co-stimulation of IL-12 and IL-18
      significantly increased miR-146a expression in bulk NK cells and in the
      CD56bright subset in a time-dependent manner, correlating with augmented IFN
      gamma production. These data suggest that miR-146a plays a negative role in IFN
      gamma production by human NK cells and this miRNA may be critical in preventing
      NK cells from being super activated and overproducing IFN-gamma.

PMID- 29593707
TI  - The Immunomodulatory Effects of Macrolides-A Systematic Review of the Underlying
      Mechanisms.
AB  - Background: The mechanisms underlying the non-antimicrobial immunomodulatory
      properties of macrolides are not well understood. Objectives: To systematically
      review the evidence for the immunomodulatory properties of macrolides in humans
      and to describe the underlying mechanism and extent of their influence on the
      innate and adaptive immune system. Methods: A systematic literature search was
      done in MEDLINE using the OVID interface from 1946 to December 2016 according to
      the preferred reporting items for systematic reviews and meta-analysis (PRISMA).
      Original articles investigating the influence of four macrolides (azithromycin,
      clarithromycin, erythromycin, and roxithromycin) on immunological markers in
      humans were included. Results: We identified 22 randomized, controlled trials, 16
      prospective cohort studies, and 8 case-control studies investigating 47 different
      immunological markers (186 measurements) in 1,834 participants. The most
      frequently reported outcomes were a decrease in the number of neutrophils, and
      the concentrations of neutrophil elastase, interleukin (IL)-8, IL-6, IL-1beta,
      tumor necrosis factor (TNF)-alpha, eosinophilic cationic protein, and matrix
      metalloproteinase 9. Inhibition of neutrophil function was reported more
      frequently than eosinophil function. A decrease in T helper (Th) 2 cells
      cytokines (IL-4, IL-5, IL-6) was reported more frequently than a decrease in Th1
      cytokines (IL-2, INF-gamma). Conclusion: Macrolides influence a broad range of
      immunological mechanisms resulting in immunomodulatory effects. To optimize the
      treatment of chronic inflammatory diseases by macrolides, further studies are
      necessary, particularly comparing different macrolides and dose effect
      relationships.

PMID- 29593708
TI  - Mucosal Delivery of Fusion Proteins with Bacillus subtilis Spores Enhances
      Protection against Tuberculosis by Bacillus Calmette-Guerin.
AB  - Tuberculosis (TB) is the most deadly infectious disease in existence, and the
      only available vaccine, Bacillus Calmette-Guerin (BCG), is almost a century old
      and poorly protective. The immunological complexity of TB, coupled with rising
      resistance to antimicrobial therapies, necessitates a pipeline of diverse novel
      vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion
      protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B,
      ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose
      Mtb aerosol challenge model. Mice were primed with subcutaneous BCG, followed by
      mucosal booster immunizations with Spore-FP1. We show that Spore-FP1 enhanced
      pulmonary control of Mtb, as evidenced by reduced bacterial burdens in the lungs.
      This was associated with elevated antigen-specific IgG and IgA titers in the
      serum and lung mucosal surface, respectively. Spore-FP1 immunization generated
      superior antigen-specific memory T-cell proliferation in both CD4+ and CD8+
      compartments, alongside bolstered Th1-, Th17-, and Treg-type cytokine production,
      compared to BCG immunization alone. CD69+CD103+ tissue resident memory T-cells
      (Trm) were found within the lung parenchyma after mucosal immunization with Spore
      FP1, confirming the advantages of mucosal delivery. Our data show that Spore-FP1
      is a promising new TB vaccine that can successfully augment protection and
      immunogenicity in BCG-primed animals.

PMID- 29593709
TI  - Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular
      Trap Formation and Promotes Apoptosis.
AB  - Tonicity of saline (NaCl) is important in regulating cellular functions and
      homeostasis. Hypertonic saline is administered to treat many inflammatory
      diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET)
      formation, or NETosis, is associated with many pathological conditions including
      chronic inflammation. Despite the known therapeutic benefits of hypertonic
      saline, its underlying mechanisms are not clearly understood. Therefore, we aimed
      to elucidate the effects of hypertonic saline in modulating NETosis. For this
      purpose, we purified human neutrophils and induced NETosis using agonists such as
      diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial
      cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and
      ionomycin from Streptomyces conglobatus), and bacteria (Pseudomonas aeruginosa
      and Staphylococcus aureus). We then analyzed neutrophils and NETs using Sytox
      green assay, immunostaining of NET components and apoptosis markers, confocal
      microscopy, and pH sensing reagents. This study found that hypertonic NaCl
      suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)
      dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and
      O128:B12), and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA-
      induced reactive oxygen species production. It was determined that supplementing
      H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent
      NETosis. Many of the aforementioned suppressive effects were observed in the
      presence of equimolar concentrations of choline chloride and osmolytes (d
      mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic
      saline suppresses NOX2-dependent NETosis is via neutrophil dehydration.
      Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils.
      We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent
      NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent
      NETosis. Although hypertonic saline partially suppresses ionomycin-induced
      NETosis, it enhances A23187-induced NETosis, and it does not alter S. aureus
      induced NETosis. Overall, this study determined that hypertonic saline suppresses
      NOX2-dependent NETosis induced by several agonists; in contrast, it has variable
      effects on neutrophil death induced by NOX2-independent NETosis agonists. These
      findings are important in understanding the regulation of NETosis and apoptosis
      in neutrophils.

PMID- 29593710
TI  - Heterologous Prime-Boost Combinations Highlight the Crucial Role of Adjuvant in
      Priming the Immune System.
AB  - The induction and modulation of the immune response to vaccination can be
      rationally designed by combining different vaccine formulations for priming and
      boosting. Here, we investigated the impact of heterologous prime-boost approaches
      on the vaccine-specific cellular and humoral responses specific for a
      mycobacterial vaccine antigen. C57BL/6 mice were primed with the chimeric vaccine
      antigen H56 administered alone or with the CAF01 adjuvant, and boosted with H56
      alone, or combined with CAF01 or with the squalene-based oil-in-water emulsion
      adjuvant (o/w squalene). A strong secondary H56-specific CD4+ T cell response was
      recalled by all the booster vaccine formulations when mice had been primed with
      H56 and CAF01, but not with H56 alone. The polyfunctional nature of T helper
      cells was analyzed and visualized with the multidimensional flow cytometry
      FlowSOM software, implemented as a package of the R environment. A similar
      cytokine profile was detected in groups primed with H56 + CAF01 and boosted with
      or without adjuvant, except for some clusters of cells expressing high level of
      IL-17 together with TNF-alpha, IL-2, and IFN-gamma, that were significantly
      upregulated only in groups boosted with the adjuvants. On the contrary, the
      comparison between groups primed with or without the adjuvant showed a completely
      different clusterization of cells, strengthening the impact of the formulation
      used for primary immunization on the profiling of responding cells. The presence
      of the CAF01 adjuvant in the priming formulation deeply affected also the
      secondary humoral response, especially in groups boosted with H56 alone or o/w
      squalene. In conclusion, the presence of CAF01 adjuvant in the primary
      immunization is crucial for promoting primary T and B cell responses that can be
      efficiently reactivated by booster immunization also performed with antigen
      alone.

PMID- 29593712
TI  - Mitochondrial Sirtuin 4 Resolves Immune Tolerance in Monocytes by Rebalancing
      Glycolysis and Glucose Oxidation Homeostasis.
AB  - The goal of this investigation was to define the molecular mechanism underlying
      physiologic conversion of immune tolerance to resolution of the acute
      inflammatory response, which is unknown. An example of this knowledge gap and its
      clinical importance is the broad-based energy deficit and immunometabolic
      paralysis in blood monocytes from non-survivors of human and mouse sepsis that
      precludes sepsis resolution. This immunometabolic dysregulation is biomarked by
      ex vivo endotoxin tolerance to increased glycolysis and TNF-alpha expression. To
      investigate how tolerance switches to resolution, we adapted our previously
      documented models associated with acute inflammatory, immune, and metabolic
      reprogramming that induces endotoxin tolerance as a model of sepsis in human
      monocytes. We report here that mitochondrial sirtuin 4 (SIRT4) physiologically
      breaks tolerance and resolves acute inflammation in human monocytes by
      coordinately reprogramming of metabolism and bioenergetics. We find that
      increased SIRT4 mRNA and protein expression during immune tolerance counters the
      increase in pyruvate dehydrogenase kinase 1 (PDK1) and SIRT1 that promote
      tolerance by switching glucose-dependent support of immune resistance to fatty
      acid oxidation support of immune tolerance. By decreasing PDK1, pyruvate
      dehydrogenase complex reactivation rebalances mitochondrial respiration, and by
      decreasing SIRT1, SIRT4 represses fatty acid oxidation. The precise mechanism for
      the mitochondrial SIRT4 nuclear feedback is unclear. Our findings are consistent
      with a new concept in which mitochondrial SIRT4 directs the axis that controls
      anabolic and catabolic energy sources.

PMID- 29593711
TI  - Regenerating Immunotolerance in Multiple Sclerosis with Autologous Hematopoietic
      Stem Cell Transplant.
AB  - Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system
      where evidence implicates an aberrant adaptive immune response in the accrual of
      neurological disability. The inflammatory phase of the disease responds to
      immunomodulation to varying degrees of efficacy; however, no therapy has been
      proven to arrest progression of disability. Recently, more intensive therapies,
      including immunoablation with autologous hematopoietic stem cell transplantation
      (AHSCT), have been offered as a treatment option to retard inflammatory disease,
      prior to patients becoming irreversibly disabled. Empirical clinical observations
      support the notion that the immune reconstitution (IR) that occurs following
      AHSCT is associated with a sustained therapeutic benefit; however, neither the
      pathogenesis of MS nor the mechanism by which AHSCT results in a therapeutic
      benefit has been clearly delineated. Although the antigenic target of the
      aberrant immune response in MS is not defined, accumulated data suggest that IR
      following AHSCT results in an immunotolerant state through deletion of pathogenic
      clones by a combination of direct ablation and induction of a lymphopenic state
      driving replicative senescence and clonal attrition. Restoration of
      immunoregulation is evidenced by changes in regulatory T cell populations
      following AHSCT and normalization of genetic signatures of immune homeostasis.
      Furthermore, some evidence exists that AHSCT may induce a rebooting of thymic
      function and regeneration of a diversified naive T cell repertoire equipped to
      appropriately modulate the immune system in response to future antigenic
      challenge. In this review, we discuss the immunological mechanisms of IR
      therapies, focusing on AHSCT, as a means of recalibrating the dysfunctional
      immune response observed in MS.

PMID- 29593713
TI  - Variable Extent of Lineage-Specificity and Developmental Stage-Specificity of
      Cohesin and CCCTC-Binding Factor Binding Within the Immunoglobulin and T Cell
      Receptor Loci.
AB  - CCCTC-binding factor (CTCF) is largely responsible for the 3D architecture of the
      genome, in concert with the action of cohesin, through the creation of long-range
      chromatin loops. Cohesin is hypothesized to be the main driver of these long
      range chromatin interactions by the process of loop extrusion. Here, we performed
      ChIP-seq for CTCF and cohesin in two stages each of T and B cell differentiation
      and examined the binding pattern in all six antigen receptor (AgR) loci in these
      lymphocyte progenitors and in mature T and B cells, ES cells, and fibroblasts.
      The four large AgR loci have many bound CTCF sites, most of which are only
      occupied in lymphocytes, while only the CTCF sites at the end of each locus near
      the enhancers or J genes tend to be bound in non-lymphoid cells also. However,
      despite the generalized lymphocyte restriction of CTCF binding in AgR loci, the
      Igkappa locus is the only locus that also shows significant lineage-specificity
      (T vs. B cells) and developmental stage-specificity (pre-B vs. pro-B) in CTCF
      binding. We show that cohesin binding shows greater lineage- and stage
      specificity than CTCF at most AgR loci, providing more specificity to the loops.
      We also show that the culture of pro-B cells in IL7, a common practice to expand
      the number of cells before ChIP-seq, results in a CTCF-binding pattern resembling
      pre-B cells, as well as other epigenetic and transcriptional characteristics of
      pre-B cells. Analysis of the orientation of the CTCF sites show that all sites
      within the large V portions of the Igh and TCRbeta loci have the same
      orientation. This suggests either a lack of requirement for convergent CTCF sites
      creating loops, or indicates an absence of any loops between CTCF sites within
      the V region portion of those loci but only loops to the convergent sites at the
      D-J-enhancer end of each locus. The V region portions of the Igkappa and
      TCRalpha/delta loci, by contrast, have CTCF sites in both orientations, providing
      many options for creating CTCF-mediated convergent loops throughout the loci.
      CTCF/cohesin loops, along with transcription factors, drives contraction of AgR
      loci to facilitate the creation of a diverse repertoire of antibodies and T cell
      receptors.

PMID- 29593714
TI  - Bacterial and Pneumocystis Infections in the Lungs of Gene-Knockout Rabbits with
      Severe Combined Immunodeficiency.
AB  - Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of
      rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1,
      RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (
      /y) F1 animals demonstrated severe combined immunodeficiency (SCID),
      characterized by absence or pronounced hypoplasia of the thymus and splenic white
      pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood.
      Complete blood count analysis showed severe leukopenia and lymphocytopenia
      accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID
      rabbits universally succumbed to lung infections following weaning. Pathology
      examination revealed severe heterophilic bronchopneumonia caused by Bordetella
      bronchiseptica in several animals, but a consistent feature of lung lesions in
      all animals was a severe interstitial pneumonia caused by Pneumocystis
      oryctolagi, as confirmed by histological examination and PCR analysis of
      Pneumocystis genes. The results of this study suggest that these SCID rabbits
      could serve as a useful model for human SCID to investigate the disease
      pathogenesis and the development of gene and drug therapies.

PMID- 29593715
TI  - Comparative Analysis of the Regulatory T Cells Dynamics in Peripheral Blood in
      Human and Porcine Polytrauma.
AB  - Background: Severely injured patients experience substantial immunological stress
      in the aftermath of traumatic insult, which often results in systemic immune
      dysregulation. Regulatory T cells (Treg) play a key role in the suppression of
      the immune response and in the maintenance of immunological homeostasis. Little
      is known about their presence and dynamics in blood after trauma, and nothing is
      known about Treg in the porcine polytrauma model. Here, we assessed different
      subsets of Treg in trauma patients (TP) and compared those to either healthy
      volunteers (HV) or data from porcine polytrauma. Methods: Peripheral blood was
      withdrawn from 20 TP with injury severity score (ISS) >=16 at the admittance to
      the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV
      were included as controls (ctrl). The porcine polytrauma model consisted of a
      femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting
      in an ISS of 27. After polytrauma, the animals underwent resuscitation and
      surgical fracture fixation. Blood samples were withdrawn before and immediately
      after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+,
      CD4+CD25+FoxP3+, CD4+CD25+CD127-, and CD4+CD25+CD127-FoxP3+ were characterized by
      flow cytometry. Results: Absolute cell counts of leukocytes were significantly
      increasing after trauma, and again decreasing in the follow-up in human and
      porcine samples. The proportion of human Treg in the peripheral blood of TP
      admitted to the ED was lower when compared to HV. Their numbers did not recover
      until 72 h after trauma. Comparable data were found for all subsets. The
      situation in the porcine trauma model was comparable with the clinical data. In
      porcine peripheral blood before trauma, we could identify Treg with the typical
      immunophenotype (CD4+CD25+CD127-), which were virtually absent immediately after
      trauma. Similar to the human situation, most of these cells expressed FoxP3, as
      assessed by intracellular FACS stain. Conclusion: Despite minor percental
      differences in the recovery of Treg populations after trauma, our findings show a
      comparable decrease of Treg early after polytrauma, and strengthen the
      immunological significance of the porcine polytrauma model. Furthermore, the Treg
      subpopulation CD4+CD25+CD127- was characterized in porcine samples.

PMID- 29593716
TI  - Mycobacterium tuberculosis Infection and Innate Responses in a New Model of Lung
      Alveolar Macrophages.
AB  - Lung alveolar macrophages (AMs) are in the first line of immune defense against
      respiratory pathogens and play key roles in the pathogenesis of Mycobacterium
      tuberculosis (Mtb) in humans. Nevertheless, AMs are available only in limited
      amounts for in vitro studies, which hamper the detailed molecular understanding
      of host-Mtb interactions in these macrophages. The recent establishment of the
      self-renewing and primary Max Planck Institute (MPI) cells, functionally very
      close to lung AMs, opens unique opportunities for in vitro studies of host
      pathogen interactions in respiratory diseases. Here, we investigated the
      suitability of MPI cells as a host cell system for Mtb infection. Bacterial,
      cellular, and innate immune features of MPI cells infected with Mtb were
      characterized. Live bacteria were readily internalized and efficiently replicated
      in MPI cells, similarly to primary murine macrophages and other cell lines. MPI
      cells were also suitable for the determination of anti-tuberculosis (TB) drug
      activity. The primary innate immune response of MPI cells to live Mtb showed
      significantly higher and earlier induction of the pro-inflammatory cytokines
      TNFalpha, interleukin 6 (IL-6), IL-1alpha, and IL-1beta, as compared to
      stimulation with heat-killed (HK) bacteria. MPI cells previously showed a lack of
      induction of the anti-inflammatory cytokine IL-10 to a wide range of stimuli,
      including HK Mtb. By contrast, we show here that live Mtb is able to induce
      significant amounts of IL-10 in MPI cells. Autophagy experiments using light
      chain 3B immunostaining, as well as LysoTracker labeling of acidic vacuoles,
      demonstrated that MPI cells efficiently control killed Mtb by elimination through
      phagolysosomes. MPI cells were also able to accumulate lipid droplets in their
      cytoplasm following exposure to lipoproteins. Collectively, this study
      establishes the MPI cells as a relevant, versatile host cell model for TB
      research, allowing a deeper understanding of AMs functions in this pathology.

PMID- 29593718
TI  - Secretion of the Phosphorylated Form of S100A9 from Neutrophils Is Essential for
      the Proinflammatory Functions of Extracellular S100A8/A9.
AB  - S100A8 and S100A9 are members of the S100 family of cytoplasmic EF-hand Ca2+
      binding proteins and are abundantly expressed in the cytosol of neutrophils. In
      addition to their intracellular roles, S100A8/A9 can be secreted in the
      extracellular environment and are considered as alarmins able to amplify the
      inflammatory response. The intracellular activity of S100A8/A9 was shown to be
      regulated by S100A9 phosphorylation, but the importance of this phosphorylation
      on the extracellular activity of S100A8/A9 has not yet been extensively studied.
      Our work focuses on the impact of the phosphorylation state of secreted S100A9 on
      the proinflammatory function of neutrophils. In a first step, we characterized
      the secretion of S100A8/A9 in different stimulatory conditions and investigated
      the phosphorylation state of secreted S100A9. Our results on neutrophil-like
      differentiated HL-60 (dHL-60) cells and purified human neutrophils showed a time
      dependent secretion of S100A8/A9 when induced by phorbol 12-myristoyl 13-acetate
      and this secreted S100A9 was found in a phosphorylated form. Second, we evaluated
      the impact of this phosphorylation on proinflammatory cytokine expression and
      secretion in dHL-60 cells. Time course experiments with purified unphosphorylated
      or phosphorylated S100A8/A9 were performed and the expression and secretion
      levels of interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor alpha,
      CCL2, CCL3, CCL4, and CXCL8 were measured by real-time PCR and cytometry bead
      array, respectively. Our results demonstrate that only the phosphorylated form of
      the complex induces proinflammatory cytokine expression and secretion. For the
      first time, we provide evidence that S100A8/PhosphoS100A9 is inducing cytokine
      secretion through toll-like receptor 4 signaling.

PMID- 29593717
TI  - Tumor Necrosis Factor alpha and Regulatory T Cells in Oncoimmunology.
AB  - Tumor necrosis factor alpha (TNF) is a potent pro-inflammatory cytokine that has
      deleterious effect in some autoimmune diseases, which led to the use of anti-TNF
      drugs in some of these diseases. However, some rare patients treated with these
      drugs paradoxically develop an aggravation of their disease or new onset
      autoimmunity, revealing an immunosuppressive facet of TNF. A possible mechanism
      of this observation is the direct and positive effect of TNF on regulatory T
      cells (Tregs) through its binding to the TNF receptor type 2 (TNFR2). Indeed, TNF
      is able to increase expansion, stability, and possibly function of Tregs via
      TNFR2. In this review, we discuss the role of TNF in graft-versus-host disease as
      an example of the ambivalence of this cytokine in the pathophysiology of an
      immunopathology, highlighting the therapeutic potential of triggering TNFR2 to
      boost Treg expansion. We also describe new targets in immunotherapy of cancer,
      emphasizing on the putative suppressive effect of TNF in antitumor immunity and
      of the interest of blocking TNFR2 to regulate the Treg compartment.

PMID- 29593719
TI  - Human Milk Oligosaccharide 2'-Fucosyllactose Improves Innate and Adaptive
      Immunity in an Influenza-Specific Murine Vaccination Model.
AB  - Background: Human milk is uniquely suited to provide optimal nutrition and immune
      protection to infants. Human milk oligosaccharides are structural complex and
      diverse consisting of short chain and long chain oligosaccharides typically
      present in a 9:1 ratio. 2'-Fucosyllactose (2'FL) is one of the most prominent
      short chain oligosaccharides and is associated with anti-infective capacity of
      human milk. Aim: To determine the effect of 2'FL on vaccination responsiveness
      (both innate and adaptive) in a murine influenza vaccination model and elucidate
      mechanisms involved. Methods: A dose range of 0.25-5% (w/w) dietary 2'FL was
      provided to 6-week-old female C57Bl/6JOlaHsd mice 2 weeks prior primary and
      booster vaccination until the end of the experiment. Intradermal (i.d.) challenge
      was performed to measure the vaccine-specific delayed-type hypersensitivity
      (DTH). Antigen-specific antibody levels in serum as well as immune cell
      populations within several organs were evaluated using ELISA and flow cytometry,
      respectively. In an ex vivo restimulation assay, spleen cells were cocultured
      with influenza-loaded bone marrow-derived dendritic cells (BMDCs) to study the
      effects of 2'FL on vaccine-specific CD4+ and CD8+ T-cell proliferation and
      cytokine secretions. Furthermore, the direct immune regulatory effects of 2'FL
      were confirmed using in vitro BMDCs T-cell cocultures. Results: Dietary 2'FL
      significantly (p < 0.05) enhanced vaccine specific DTH responses accompanied by
      increased serum levels of vaccine-specific immunoglobulin (Ig) G1 and IgG2a in a
      dose-dependent manner. Consistently, increased activation marker (CD27)
      expression on splenic B-cells was detected in mice receiving 2'FL as compared to
      control mice. Moreover, proliferation of vaccine-specific CD4+ and CD8+ T-cells,
      as well as interferon-gamma production after ex vivo restimulation were
      significantly increased in spleen cells of mice receiving 2'FL as compared to
      control mice, which were in line with changes detected within dendritic cell
      populations. Finally, we confirmed a direct effect of 2'FL on the maturation
      status and antigen presenting capacity of BMDCs. Conclusion: Dietary intervention
      with 2'FL improves both humoral and cellular immune responses to vaccination in
      mice, which might be attributed in part to the direct effects of 2'FL on immune
      cell differentiation.

PMID- 29593720
TI  - The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple
      Sclerosis Patients: A Novel Potential Disease Biomarker.
AB  - Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease
      of the central nervous system. It was previously shown that toll-like receptor
      (TLR)-2 signaling plays a key role in the murine experimental autoimmune
      encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T
      cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we
      sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS
      patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly
      elevated in sera of MS patients (n = 21), in both relapse and remission, compared
      to healthy controls (HC) (n = 24). This was not associated with the acute phase
      reaction (APR) as measured by serum C-reactive protein (CRP) level, which was
      similarly increased in MS patients compared to controls. An independent
      validation cohort from a different ethnic background showed a similar upward
      trend in mean sTLR2 values in relapsing-remitting MS (RRMS) patients, and
      significant differences in sTLR2 values between patients and HC were preserved
      when the data from the two cohorts were pooled together (n = 41 RRMS and 44 HC, P
      = 0.0006). TLR2-stimulants, measured using a human embryonic kidney (HEK)-293
      cells transfectant reporter assay, were significantly higher in urine of MS
      patients than HC. A screen of several common urinary tract infections (UTI)
      related organisms showed strong induction of TLR2-signaling in the same assay.
      Taken together, these results indicate that two different markers of TLR2
      activity-urinary TLR2-stimulants and serum sTLR2 levels-are significantly
      elevated in MS patients compared to HC.

PMID- 29593721
TI  - Vitamin D in Human Immunodeficiency Virus Infection: Influence on Immunity and
      Disease.
AB  - People living with human immunodeficiency virus (HIV) infection typically have
      hypovitaminosis D, which is linked to a large number of pathologies, including
      immune disorders and infectious diseases. Vitamin D (VitD) is a key regulator of
      host defense against infections by activating genes and pathways that enhance
      innate and adaptive immunity. VitD mediates its biological effects by binding to
      the Vitamin D receptor (VDR), and activating and regulating multiple cellular
      pathways. Single nucleotide polymorphisms in genes from those pathways have been
      associated with protection from HIV-1 infection. High levels of VitD and VDR
      expression are also associated with natural resistance to HIV-1 infection.
      Conversely, VitD deficiency is linked to more inflammation and immune activation,
      low peripheral blood CD4+ T-cells, faster progression of HIV disease, and shorter
      survival time in HIV-infected patients. VitD supplementation and restoration to
      normal values in HIV-infected patients may improve immunologic recovery during
      combination antiretroviral therapy, reduce levels of inflammation and immune
      activation, and increase immunity against pathogens. Additionally, VitD may
      protect against the development of immune reconstitution inflammatory syndrome
      events, pulmonary tuberculosis, and mortality among HIV-infected patients. In
      summary, this review suggests that VitD deficiency may contribute to the
      pathogenesis of HIV infection. Also, VitD supplementation seems to reverse some
      alterations of the immune system, supporting the use of VitD supplementation as
      prophylaxis, especially in individuals with more severe VitD deficiency.

PMID- 29593722
TI  - Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by
      the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis
      through ACAT Upregulation.
AB  - The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host
      relies on numerous immune evasion strategies, such as the deregulation of the
      lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the
      specific host factors leading to the foamy phenotype of Mtb-infected macrophages
      remain unknown. Herein, we aimed to address whether host cytokines contribute to
      FM formation in the context of Mtb infection. Our approach is based on the use of
      an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological
      source of local factors released during Mtb infection. We found that TB-PE
      induced FM differentiation as observed by the increase in lipid bodies,
      intracellular cholesterol, and expression of the scavenger receptor CD36, as well
      as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly,
      interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all
      these parameters. Moreover, we observed a positive correlation between the levels
      of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB
      patients, demonstrating that FM differentiation occurs within the pleural
      environment. Downstream of IL-10 signaling, we noticed that the transcription
      factor signal transducer and activator of transcription 3 was activated by TB-PE,
      and its chemical inhibition prevented the accumulation of lipid bodies and ACAT
      expression in macrophages. In terms of the host immune response, TB-PE-treated
      macrophages displayed immunosuppressive properties and bore higher bacillary
      loads. Finally, we confirmed our results using bone marrow-derived macrophage
      from IL-10-/- mice demonstrating that IL-10 deficiency partially prevented foamy
      phenotype induction after Mtb lipids exposure. In conclusion, our results
      evidence a role of IL-10 in promoting the differentiation of FM in the context of
      Mtb infection, contributing to our understanding of how alterations of the host
      metabolic factors may favor pathogen persistence.

PMID- 29593723
TI  - Analyzing Immunoglobulin Repertoires.
AB  - Somatic assembly of T cell receptor and B cell receptor (BCR) genes produces a
      vast diversity of lymphocyte antigen recognition capacity. The advent of
      efficient high-throughput sequencing of lymphocyte antigen receptor genes has
      recently generated unprecedented opportunities for exploration of adaptive immune
      responses. With these opportunities have come significant challenges in
      understanding the analysis techniques that most accurately reflect underlying
      biological phenomena. In this regard, sample preparation and sequence analysis
      techniques, which have largely been borrowed and adapted from other fields,
      continue to evolve. Here, we review current methods and challenges of library
      preparation, sequencing and statistical analysis of lymphocyte receptor
      repertoire studies. We discuss the general steps in the process of immune
      repertoire generation including sample preparation, platforms available for
      sequencing, processing of sequencing data, measurable features of the immune
      repertoire, and the statistical tools that can be used for analysis and
      interpretation of the data. Because BCR analysis harbors additional complexities,
      such as immunoglobulin (Ig) (i.e., antibody) gene somatic hypermutation and class
      switch recombination, the emphasis of this review is on Ig/BCR sequence analysis.

PMID- 29593725
TI  - Perilipin 1 Mediates Lipid Metabolism Homeostasis and Inhibits Inflammatory
      Cytokine Synthesis in Bovine Adipocytes.
AB  - Dairy cows with ketosis displayed lipid metabolic disorder and high inflammatory
      levels. Adipose tissue is an active lipid metabolism and endocrine tissue and is
      closely related to lipid metabolism homeostasis and inflammation. Perilipin 1
      (PLIN1), an adipocyte-specific lipid-coated protein, may be involved in the above
      physiological function. The aim of this study is to investigate the role of PLIN1
      in lipid metabolism regulation and inflammatory factor synthesis in cow
      adipocytes. The results showed that PLIN1 overexpression upregulated the
      expression of fatty acid and triglyceride (TAG) synthesis molecule sterol
      regulator element-binding protein-1c (SREBP-1c) and its target genes,
      diacylglycerol acyltransferase (DGAT) 1, and DGAT2, but inhibited the expression
      of lipolysis enzymes hormone-sensitive lipase (HSL) and CGI-58 for adipose
      triglyceride lipase (ATGL), thus augmenting the fatty acids and TAG synthesis and
      inhibiting lipolysis. Importantly, PLIN1 overexpression inhibited the activation
      of the NF-kappaB inflammatory pathway and decreased the expression and content of
      tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), and
      interleukin 6 (IL-6) induced by lipopolysaccharide. Conversely, PLIN1 silencing
      inhibited TAG synthesis, promoted lipolysis, and overinduced the activation of
      the NF-kappaB inflammatory pathway in cow adipocytes. In ketotic cows, the
      expression of PLIN1 was markedly decreased, whereas lipid mobilization, NF-kappaB
      pathway, and downstream inflammatory cytokines were overinduced in adipose
      tissue. Taken together, these results indicate that PLIN1 can maintain lipid
      metabolism homeostasis and inhibit the NF-kappaB inflammatory pathway in
      adipocytes. However, low levels of PLIN1 reduced the inhibitory effect on fat
      mobilization, NF-kappaB pathway, and inflammatory cytokine synthesis in ketotic
      cows.

PMID- 29593724
TI  - miRNome Expression Analysis Reveals New Players on Leprosy Immune
      Physiopathology.
AB  - Leprosy remains as a public health problem and its physiopathology is still not
      fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere
      with mRNA to regulate gene expression. A few studies using DNA chip microarrays
      have explored the expression of miRNA in leprosy patients using a predetermined
      set of genes as targets, providing interesting findings regarding the regulation
      of immune genes. However, using a predetermined set of genes restricted the
      possibility of finding new miRNAs that might be involved in different mechanisms
      of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous
      (LL) patients using both blood and lesional biopsies from classical leprosy
      patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary
      Dermatology in the State of Para and compared them with healthy subjects. Using a
      set of tools to correlate significantly differentially expressed miRNAs with
      their gene targets, we identified possible interactions and networks of miRNAs
      that might be involved in leprosy immunophysiopathology. Using this approach, we
      showed that the leprosy miRNA profile in blood is distinct from that in lesional
      skin as well as that four main groups of genes are the targets of leprosy miRNA:
      (1) recognition and phagocytosis, with activation of immune effector cells, where
      the immunosuppressant profile of LL and immunoresponsive profile of TT are
      clearly affected by miRNA expression; (2) apoptosis, with supportive data for an
      antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3)
      Schwann cells (SCs), demyelination and epithelial-mesenchymal transition (EMT),
      supporting a role for different developmental or differentiation gene families,
      such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain,
      revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in
      the loss of sensation or leprosy pain, indicating possible new therapeutic
      targets. Additionally, AQP1 may also be involved in skin dryness and loss of
      elasticity, which are well known signs of leprosy but with unrecognized
      physiopathology. In sum, miRNA expression reveals new aspects of leprosy
      immunophysiopathology, especially on the regulation of the immune system,
      apoptosis, SC demyelination, EMT, and neuropathic pain.

PMID- 29593726
TI  - Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early
      Graft Thrombosis after Renal Transplantation in the Clinical Practice: A
      Multicenter and Prospective Study.
AB  - Background: Graft thrombosis is a devastating complication after renal
      transplantation. We recently described the association of anti-beta-2
      glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by
      thrombosis in a monocenter study. Methods: Multicenter prospective observational
      cohort study. Setting and participants: Seven hundred forty patients from five
      hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were
      prospectively followed-up for 10 years. Outcomes: Early graft loss and graft loss
      by thrombosis. Measurements: The presence of IgA anti-B2GP1 antibodies in
      pretransplant serum was examined using the same methodology in all the patients.
      Results: At transplantation, 288 patients were positive for IgA-B2GP1 (39%, Group
      1) and the remaining were negative (Group-2). Graft loss at 6 months was higher
      in Group-1 (12.5 vs. 4.2% p < 0.001), vessel thrombosis being the most frequent
      cause of early graft loss, especially in Group-1 (6.9 vs. 0.4% p < 0.001). IgA
      aB2GP1 was the most important independent risk factor for graft thrombosis
      (hazard ratio: 13.83; 95% CI: 3.17-60.27, p < 0.001). Furthermore, the, presence
      of IgA-aB2GP1 was associated with early graft loss and delayed graft function. At
      10 years, survival figures were also lower in Group-1: graft survival was lower
      compared with Group-2 (60.4 vs. 76.8%, p < 0.001). Mortality was significantly
      higher in Group-1 (19.8 vs. 12.2%, p = 0.005). Limitations: Patients were
      obtained during a 3-year period (1 January 2000-31 December 2002) and kidneys
      were only transplanted from brain-dead donors. Nowadays, the patients are older
      and the percentage of sensitized and retransplants is high. Conclusion: In a
      prospective observational multicenter study, we were able to corroborate that
      pretransplant presence of IgA-aB2GP1 was the main risk factor for graft
      thrombosis and early graft loss. Therefore, a prospective study is needed to
      evaluate the efficacy and safety of prophylactic anticoagulation to avoid this
      severe complication.

PMID- 29593727
TI  - Effect of VH-VL Families in Pertuzumab and Trastuzumab Recombinant Production,
      Her2 and FcgammaIIA Binding.
AB  - Many therapeutic antibodies are humanized from animal sources. In the
      humanization process, complementarity determining region grafting is tedious and
      highly prone to failure. With seven known VH families, and up to six known kappa
      VL families, there are choices aplenty. However, the functions of these families
      remain largely enigmatic. To study the role of these V-region families, we made
      84 recombinant combinations of the various VH and VL family whole IgG1 variants
      of both Trastuzumab and Pertuzumab. We managed to purify 66 of these to
      investigate the biophysical characteristics: recombinant protein production, and
      both Her2 and FcgammaIIA binding. Our findings revealed combinations that showed
      improved recombinant antibody production and both antigen and receptor binding
      kinetics. These findings show the need to rethink antibodies as a whole protein,
      relooking of the functions of the antibody domains, and the need to include
      immunoglobulin receptor investigations for effective antibody therapeutics
      development.

PMID- 29593728
TI  - The Acid-Base Balance and Gender in Inflammation: A Mini-Review.
AB  - In humans, acid-base balance is crucial to cell homeostasis. Acidosis is observed
      in numerous inflammatory processes, primarily acute conditions such as sepsis,
      trauma, or acute respiratory distress where females tend to exhibit better
      prognosis compared with males. The mechanisms underlying these gender-dependent
      differences are multiple, probably involving hormonal and genetic factors,
      particularly the X chromosome. Although pH influences multiple immunological
      functions, gender differences in acid-base balance have been poorly investigated.
      In this review, we provide an update on gender differences in human
      susceptibility to inflammatory diseases. We additionally discuss the potential
      impact of acid-base balance on the gender bias of the inflammatory response in
      view of our recent observation that girls present higher neutrophilic
      inflammation and lower pH with a trend toward better prognosis in severe sepsis.
      We also highlight the potent role played by endothelial cells in gender
      differences of inflammation through activation of proton-sensing G protein
      coupled receptors.

PMID- 29593730
TI  - CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation
      of ID3.
AB  - CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms
      in inflammatory responses, with involvement in processes such as infection,
      atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory
      cytokine profile in response to TLR activation. In the present study, we
      questioned whether CD5L is able to influence human macrophage plasticity, and
      drive its polarization toward any specific phenotype. We compared CD5L-induced
      phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in
      human monocytes. Phenotypic markers were quantified by RT-qPCR and flow
      cytometry, and a mathematical algorithm was built for their analysis. Moreover,
      we compared ROS production, phagocytic capacity, and inflammatory responses to
      LPS. CD5L drove cells toward a polarization similar to that induced by IL10.
      Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content
      and colocalization with acidic compartments, thereby pointing to the enhancement
      of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells
      blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In
      these cells, gene expression profiling and validation indicated the upregulation
      of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing
      reversed polarization by CD5L. Our data point to a significant contribution of
      CD5L-mediated autophagy to the induction of ID3 and provide the first evidence
      that CD5L drives macrophage polarization.

PMID- 29593729
TI  - Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin
      D, Immune Cells, and Multiple Sclerosis.
AB  - Vitamin D has a plethora of functions that are important for the maintenance of
      general health and in particular, the functional integrity of the immune system,
      such as promoting an anti-inflammatory cytokine profile and reducing the
      Treg/Th17 ratio. Multiple sclerosis (MS) is a chronic, inflammatory, and
      neurodegenerative central nervous system (CNS) disorder of probable autoimmune
      origin. MS is characterized by recurring or progressive demyelination and
      degeneration of the CNS due in part to a misguided immune response to as yet
      undefined (CNS) antigens, potentially including myelin basic protein and
      proteolipid protein. MS has also been shown to be associated significantly with
      environmental factors such as the lack of vitamin D. The role of vitamin D in the
      pathogenesis and progression of MS is complex. Recent genetic studies have shown
      that various common MS-associated risk-single-nucleotide polymorphisms (SNPs) are
      located within or in the vicinity of genes associated with the complex metabolism
      of vitamin D. The functional aspects of these genetic associations may be
      explained either by a direct SNP-associated loss- or gain-of-function in a
      vitamin D-associated gene or due to a change in the regulation of gene expression
      in certain immune cell types. The development of new genetic tools using next
      generation sequencing: e.g., chromatin immunoprecipitation sequencing (ChIP-seq)
      and the accompanying rapid progress of epigenomics has made it possible to
      recognize that the association between vitamin D and MS could be based on the
      extensive and characteristic genomic binding of the vitamin D receptor (VDR).
      Therefore, it is important to analyze comprehensively the spatiotemporal VDR
      binding patterns that have been identified using ChIP-seq in multiple immune cell
      types to reveal an integral profile of genomic VDR interaction. In summary, the
      aim of this review is to connect genomic effects vitamin D has on immune cells
      with MS and thus, to contribute to a better understanding of the influence of
      vitamin D on the etiology and the pathogenesis of this complex autoimmune
      disease.

PMID- 29593731
TI  - Transcriptional Regulation of Emergency Granulopoiesis in Leukemia.
AB  - Neutropenic conditions are prevalent in leukemia patients and are often
      associated with increased susceptibility to infections. In fact, emergency
      granulopoiesis (EG), a process regulating neutrophil homeostasis in inflammatory
      conditions and infections, may occur improperly in leukemic conditions, leading
      to reduced neutrophil counts. Unfortunately, the mechanisms central to
      dysfunctional EG remain understudied in both leukemia patients and leukemic mouse
      models. However, despite no direct studies on EG response in leukemia are
      reported, recently certain transcription factors (TFs) have been found to
      function at the crossroads of leukemia and EG. In this review, we present an
      update on TFs that can potentially govern the fate of EG in leukemia.
      Transcriptional control of Fanconi DNA repair pathway genes is also highlighted,
      as well as the newly discovered role of Fanconi proteins in innate immune
      response and EG. Identifying the TFs regulating EG in leukemia and dissecting
      their underlying mechanisms may facilitate the discovery of therapeutic drugs for
      the treatment of neutropenia.

PMID- 29593732
TI  - A Distinct T Follicular Helper Cell Subset Infiltrates the Brain in Murine
      Neuropsychiatric Lupus.
AB  - Neuropsychiatric symptoms in systemic lupus erythematosus (SLE) are not uncommon,
      yet the mechanisms underlying disease initiation and progression in the brain are
      incompletely understood. Although the role of T cells in other lupus target
      organs such as the kidney is well defined, which T cells contribute to the
      pathogenesis of neuropsychiatric SLE is not known. The present study was aimed at
      characterizing the CD4 T cell populations that are present in the choroid plexus
      (CP) of MRL/MpJ-faslpr mice, the primary site of brain infiltration in this
      classic lupus mouse model which exhibits a prominent neurobehavioral phenotype. T
      cells infiltrating the CP of MRL/MpJ-faslpr mice were characterized and subset
      identification was done by multiparameter flow cytometry. We found that the
      infiltrating CD4 T cells are activated and have an effector phenotype.
      Importantly, CD4 T cells have a T follicular helper cell (TFH) like phenotype, as
      evidenced by their surface markers and signature cytokine, IL-21. In addition,
      CD4 TFH cells also secrete significant levels of IFN-gamma and express Bcl-6,
      thereby conforming to a potentially pathogenic T helper population that can drive
      the disease progression. Interestingly, the regulatory axis comprising CD4 T
      regulatory cells is diminished. These results suggest that accumulation of CD4
      TFH in the brain of MRL/MpJ-faslpr mice may contribute to the neuropsychiatric
      manifestations of SLE, and point to this T cell subset as a possible novel
      therapeutic candidate.

PMID- 29593733
TI  - Computational Insight Into the Structural Organization of Full-Length Toll-Like
      Receptor 4 Dimer in a Model Phospholipid Bilayer.
AB  - Toll-like receptors (TLRs) are a unique category of pattern recognition receptors
      that recognize distinct pathogenic components, often utilizing the same set of
      downstream adaptors. Specific molecular features of extracellular, transmembrane
      (TM), and cytoplasmic domains of TLRs are crucial for coordinating the complex,
      innate immune signaling pathway. Here, we constructed a full-length structural
      model of TLR4-a widely studied member of the interleukin-1 receptor/TLR
      superfamily-using homology modeling, protein-protein docking, and molecular
      dynamics simulations to understand the differential domain organization of TLR4
      in a membrane-aqueous environment. Results showed that each functional domain of
      the membrane-bound TLR4 displayed several structural transitions that are
      biophysically essential for plasma membrane integration. Specifically, the
      extracellular and cytoplasmic domains were partially immersed in the upper and
      lower leaflets of the membrane bilayer. Meanwhile, TM domains tilted considerably
      to overcome the hydrophobic mismatch with the bilayer core. Our analysis
      indicates an alternate dimerization or a potential oligomerization interface of
      TLR4-TM. Moreover, the helical properties of an isolated TM dimer partly agree
      with that of the full-length receptor. Furthermore, membrane-absorbed or solvent
      exposed surfaces of the toll/interleukin-1 receptor domain are consistent with
      previous X-ray crystallography and biochemical studies. Collectively, we provided
      a complete structural model of membrane-bound TLR4 that strengthens our current
      understanding of the complex mechanism of receptor activation and adaptor
      recruitment in the innate immune signaling pathway.

PMID- 29593734
TI  - Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient
      Mice.
AB  - Background: The cuprizone (CPZ) model of multiple sclerosis (MS) was used to
      identify microRNAs (miRNAs) related to in vivo de- and remyelination. We further
      investigated the role of miR-146a in miR-146a-deficient (KO) mice: this miRNA is
      differentially expressed in MS lesions and promotes differentiation of
      oligodendrocyte precursor cells (OPCs) during remyelination, but its role has not
      been examined during demyelination. Methods: MicroRNAs were examined by Agilent
      Mouse miRNA Microarray in the corpus callosum during CPZ-induced demyelination
      and remyelination. Demyelination, axonal loss, changes in number of
      oligodendrocytes, OPCs, and macrophages/microglia was compared by
      histology/immunohistochemistry between KO and WT mice. Differential expression of
      target genes and proteins of miR-146a was analyzed in the transcriptome (4 * 44K
      Agilent Whole Mouse Genome Microarray) and proteome (liquid chromatography tandem
      mass spectrometry) of CPZ-induced de- and remyelination in WT mice. Levels of
      proinflammatory molecules in the corpus callosum were compared in WT versus KO
      mice by Meso Scale Discovery multiplex protein analysis. Results: miR-146a was
      increasingly upregulated during CPZ-induced de- and remyelination. The absence of
      miR-146a in KO mice protected against demyelination, axonal loss, body weight
      loss, and atrophy of thymus and spleen. The number of CNP+ oligodendrocytes was
      increased during demyelination in the miR-146a KO mice, while there was a trend
      of increased number of NG2+ OPCs in the WT mice. miR-146a target genes, SNAP25
      and SMAD4, were downregulated in the proteome of demyelinating corpus callosum in
      WT mice. Higher levels of SNAP25 were measured by ELISA in the corpus callosum of
      miR-146a KO mice, but there was no difference between KO and WT mice during
      demyelination. Multiplex protein analysis of the corpus callosum lysate revealed
      upregulated TNF-RI, TNF-RII, and CCL2 in the WT mice in contrast to KO mice. The
      number of Mac3+ and Iba1+ macrophages/microglia was reduced in the demyelinating
      corpus callosum of the KO mice. Conclusion: During demyelination, absence of miR
      146a reduced inflammatory responses, demyelination, axonal loss, the number of
      infiltrating macrophages, and increased the number of myelinating
      oligodendrocytes. The number of OPCs was slightly higher in the WT mice during
      remyelination, indicating a complex role of miR-146a during in vivo de- and
      remyelination.

PMID- 29593735
TI  - Involvement of Macrophage Inflammatory Protein-1 Family Members in the
      Development of Diabetic Neuropathy and Their Contribution to Effectiveness of
      Morphine.
AB  - Current investigations underline the important roles of C-C motif ligands in the
      development of neuropathic pain; however, their participation in diabetic
      neuropathy is still undefined. Therefore, the goal of our study was to evaluate
      the participation of macrophage inflammatory protein-1 (MIP-1) family members
      (CCL3, CCL4, CCL9) in a streptozotocin (STZ)-induced mouse model of diabetic
      neuropathic pain. Single intrathecal administration of each MIP-1 member (10,
      100, or 500 ng/5 MUl) in naive mice evoked hypersensitivity to mechanical (von
      Frey test) and thermal (cold plate test) stimuli. Concomitantly, protein analysis
      has shown that, 7 days following STZ injection, the levels of CCL3 and CCL9 (but
      not CCL4) are increased in the lumbar spinal cord. Performed additionally,
      immunofluorescence staining undoubtedly revealed that CCL3, CCL9, and their
      receptors (CCR1 and CCR5) are expressed predominantly by neurons. In vitro
      studies provided evidence that the observed expression of CCL3 and CCL9 may be
      partially of glial origin; however, this observation was only partially possible
      to confirm by immunohistochemical study. Single intrathecal administration of
      CCL3 or CCL9 neutralizing antibody (2 and 4 MUg/5 MUl) delayed neuropathic pain
      symptoms as measured at day 7 following STZ administration. Single intrathecal
      injection of a CCR1 antagonist (J113863; 15 and 20 MUg/5 MUl) also attenuated
      pain-related behavior as evaluated at day 7 after STZ. Both neutralizing
      antibodies, as well as the CCR1 antagonist, enhanced the effectiveness of
      morphine in STZ-induced diabetic neuropathy. These findings highlight the
      important roles of CCL3 and CCL9 in the pathology of diabetic neuropathic pain
      and suggest that they play pivotal roles in opioid analgesia.

PMID- 29593736
TI  - Type I Interferon-Independent Dendritic Cell Priming and Antitumor T Cell
      Activation Induced by a Mycoplasma fermentans Lipopeptide.
AB  - Mycoplasma fermentans-derived diacylated lipoprotein M161Ag (MALP404) is
      recognized by human/mouse toll-like receptor (TLR) 2/TLR6. Short proteolytic
      products including macrophage-activating lipopeptide 2 (MALP2) have been utilized
      as antitumor immune-enhancing adjuvants. We have chemically synthesized a short
      form of MALP2 named MALP2s (S-[2,3-bis(palmitoyloxy)propyl]-CGNNDE). MALP2 and
      MALP2s provoke natural killer (NK) cell activation in vitro but only poorly
      induce tumor regression using in vivo mouse models loading NK-sensitive tumors.
      Here, we identified the functional mechanism of MALP2s on dendritic cell (DC)
      priming and cytotoxic T lymphocyte (CTL)-dependent tumor eradication using CTL
      sensitive tumor-implant models EG7 and B16-OVA. Programmed death ligand-1 (PD-L1)
      blockade therapy in combination with MALP2s + ovalbumin (OVA) showed a
      significant additive effect on tumor growth suppression. MALP2s increased co
      stimulators CD80/86 and CD40, which were totally MyD88-dependent, with no
      participation of toll-IL-1R homology domain-containing adaptor molecule-1 or type
      I interferon signaling in DC priming. MALP2s + OVA consequently augmented
      proliferation of OVA-specific CTLs in the spleen and at tumor sites. Chemokines
      and cytolytic factors were upregulated in the tumor. Strikingly, longer duration
      and reinvigoration of CTLs in spleen and tumors were accomplished by the addition
      of MALP2s + OVA to alpha-PD-L1 antibody (Ab) therapy compared to alpha-PD-L1 Ab
      monotherapy. Then, tumors regressed better in the MALP2s/OVA combination than in
      the alpha-PD-L1 Ab monotherapy. Hence, MALP2s/tumor-associated antigens combined
      with alpha-PD-L1 Ab is a good therapeutic strategy in some mouse models.
      Unfortunately, numerous patients are still resistant to PD-1/PD-L1 blockade, and
      good DC-priming adjuvants are desired. Cytokine toxicity by MALP2s remains to be
      settled, which should be improved by chemical modification in future studies.

PMID- 29593737
TI  - Overall Downregulation of mRNAs and Enrichment of H3K4me3 Change Near Genome-Wide
      Association Study Signals in Systemic Lupus Erythematosus: Cell-Specific Effects.
AB  - This study was designed to define gene expression and H3K4me3 histone
      modifications in T cells, B cells, and monocytes in systemic lupus erythematosus
      (SLE). Array studies of total peripheral blood mononuclear cells have
      demonstrated gene expression signatures related to neutrophils, interferon, and
      other inflammatory pathways. It is not clear how consistent these effects are
      across different cell types. In this study, RNA-seq and chromatin
      immunoprecipitation-seq were utilized to identify gene expression patterns and
      H3K4me3 histone modifications related to promoter activation in SLE. Across the
      three cell types, there was 55% concordance for gene expression changes related
      to SLE. Key conserved pathways were ribosome biogenesis among upregulated genes
      and heat shock response among downregulated genes. ETS family transcription
      factors (TFs) and STAT1 were revealed as common regulators by position weight
      matrices. When epigenetic changes were leveraged with gene expression, the
      pivotal TFs ATF3 and FOS were defined with ATF3 also cross-referencing with gene
      expression-identified TFs. Genome-wide association study (GWAS) single nucleotide
      polymorphisms associated with SLE were cross-referenced with both mRNA and
      H3K4me3 changes in SLE. Baseline mRNA expression and H3K4me3 peak height was
      higher at sites that cross-referenced with GWAS signals, however, all three cell
      types exhibited an overall decrease in expression of GWAS-associated RNAs
      differentially expressed in SLE. H3K4me3 changes in SLE were also enriched in
      GWAS-associated sites. In summary, the SLE disease process is associated with
      both shared and cell-specific changes in gene expression and epigenetics.
      Surprisingly, GWAS-associated RNAs were overall markedly decreased across all
      three cell types. TF analysis identified ATF3, FOS, STAT1, and ETS family members
      as critical, all pathways with a recognized relationship to the SLE disease
      process. GWAS signals clearly mark both cell-type specific changes in SLE as well
      as concordant changes across all three cell types. Interpretation of single
      nucleotide polymorphism effects in SLE will require tissue-specific mechanistic
      studies and therapeutics will require mechanistic studies in multiple cell types.

PMID- 29593738
TI  - Prostaglandin E2 Inhibits Group 2 Innate Lymphoid Cell Activation and Allergic
      Airway Inflammation Through E-Prostanoid 4-Cyclic Adenosine Monophosphate
      Signaling.
AB  - Evidence is accumulating that group 2 innate lymphoid cells (ILC2) play an
      important role in allergic airway inflammation by producing a large amount of
      type 2 cytokines. But it remains poorly understood how its activities are
      properly controlled in vivo. Here, we demonstrated that prostaglandin E2 (PGE2)
      had a profound inhibitory effect on IL-33-induced ILC2 expansion and IL-5 and IL
      13 production in vitro. This effect was mimicked by PGE1-alcohol but attenuated
      by ONO-AE3-208, indicating a selective action through the E-prostanoid 4 (EP4)
      receptor. In the IL-33-induced asthma model, coadministration of PGE2 or PGE1
      alcohol resulted in diminished IL-5 and IL-13 production, reduced eosinophilia
      and alleviated lung pathology. In contrast, EP4-deficient mice displayed an
      exacerbated inflammatory response in another ILC2-mediated asthma model induced
      by Alternaria extract. Mechanistic studies demonstrated that the PGE2-mediated
      inhibition of ILC2 was dependent on cyclic adenosine monophosphate (cAMP)
      production. Further downstream, PGE2-EP4-cAMP signaling led to suppression of
      GATA3 and ST2 expression, which is known to be critical for ILC2 activation.
      These findings reveal a novel function of PGE2 as a negative regulator of ILC2
      activation and highlight an endogenous counter-regulatory mechanism for the
      control of innate allergic inflammatory responses.

PMID- 29593739
TI  - STAT6 Mediates Footpad Immunopathology in the Absence of IL-12p40 Following
      Infection of Susceptible BALB/c Mice With Leishmania major.
AB  - Leishmania major (L. major) parasites are intracellular parasites belong to the
      Trypanosomatidae family and are the causative agent of cutaneous leishmaniasis.
      This disease affects approximately 1.5 million per year worldwide and there is
      currently no prophylactic vaccine available. L. major is transmitted by the bite
      of an infected sandfly and has been considered for decades now as a mouse model
      of choice to identify the factors implicated in T helper (Th)1 and Th2
      polarization due to the natural resistance and susceptibility to infection of
      C57BL/6 and BALB/c mice, respectively. In this study, we refine the role of IL
      12p40 cytokine, which is implicated the development of a protective Th1 response,
      and STAT6, a transcription factor involved in the signaling via detrimental
      interleukin (IL)-4 and IL-13 associated Th2 cytokines during L. major infection
      in the BALB/c model. In the absence of STAT6 and IL-12p40 signaling, double
      knockout (DKO) susceptible BALB/c mice displayed reduced footpad swelling and
      ulcerative lesion compared to IL-12p40-/- mice upon L. major infection. Hence,
      they expressed slower upregulation of keratinocyte markers implicated in the
      inhibition of wound healing, such as keratin 6a (Krt6a) and Krt16. This coincides
      with the presence of neutrophils displaying an altered phenotype characterized by
      a lower expression of surface markers Ly6C, CD11b, and Ly6G. These neutrophils
      exhibited very lower levels of apoptosis similarly to neutrophils present in
      resistant STAT6-/- mice. Interestingly, the reduced footpad swelling in DKO mice
      is associated with a high footpad parasite level similar to susceptible IL-12p40
      /- mice. In conclusion, this study demonstrate that in the absence of both STAT6
      and IL-12p40 signaling, L. major-infected mice display smaller and less ulcerated
      lesions, which does, however, not correlate with reduced parasite load. In
      addition, the presence of neutrophils with an altered phenotype is associated
      with reduced apoptosis and delayed immunopathologies, demonstrating the
      detrimental role of STAT6 in infected susceptible BALB/c mice.

PMID- 29593740
TI  - Editorial: New Insights In Anaphylaxis.

PMID- 29593741
TI  - An ELISA Assay for Quantifying Monomeric C-Reactive Protein in Plasma.
AB  - Native C-reactive protein (nCRP) is a non-specific marker of inflammation being
      claimed as a bystander in several chronic disorders. Accumulating evidence
      indicates that nCRP dissociates to and acts primarily as the monomeric
      conformation (mCRP) at inflammatory loci. This suggests that mCRP may be a
      superior disease marker with improved specificity and clear causality to the
      underlying pathogenesis. However, the lack of a feasible assay to quantify mCRP
      in clinical samples precludes the assessment of that suggestion. Here we report
      the development of a sandwich ELISA assay for quantification of plasma mCRP using
      commercially available reagents. Our assay is reproducible and highly
      conformation-specific showing a reliable detection limit of 1 ng/mL. We further
      show that mCRP appears to be a better marker than nCRP in several skin-related
      autoimmune disorders. This assay thus provides a useful tool to examine the
      clinical significance and utility of mCRP.

PMID- 29593742
TI  - Immunotherapy With Human Gamma Delta T Cells-Synergistic Potential of Epigenetic
      Drugs?

PMID- 29593743
TI  - Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity.
AB  - Tolerance against self-antigens is regulated by a variety of cell types with
      immunoregulatory properties, such as CD1d-restricted invariant natural killer T
      (iNKT) cells. In many experimental models of autoimmunity, iNKT cells promote
      self-tolerance and protect against autoimmunity. These findings are supported by
      studies with patients suffering from autoimmune diseases. Based on these studies,
      the therapeutic potential of iNKT cells in autoimmunity has been explored. Many
      of these studies have been performed with the potent iNKT cell agonist KRN7000 or
      its structural variants. These findings have generated promising results in
      several autoimmune diseases, although mechanisms by which iNKT cells modulate
      autoimmunity remain incompletely understood. Here, we will review these
      preclinical studies and discuss the prospects for translating their findings to
      patients suffering from autoimmune diseases.

PMID- 29593744
TI  - Studies of Mast Cells: Adventures in Serendipity.
AB  - Like many of us who had the great fortune to work with Bill Paul, my science life
      was immeasurably altered by my interactions with him. Although intimidating at
      first because of his stature in the immunology world, it was soon clear that he
      not only truly cared about the specific research we were doing together, but he
      wished to convey to his trainees an approach to science that was open, always
      questioning, and infinitely fun. His enthusiasm was infectious and after my
      training with him, despite stresses due to funding and publishing hurdles, I
      never regretted the path I took. My research took a sharp turn from the studies
      of adaptive immunity I had planned on pursuing after my fellowship with Bill to a
      life long quest to understand the wonders of the mast cell, a relatively rare
      innate immune cell. This came about because Bill's curiosity and expectation of
      the unexpected allowed him to view, in retrospect, a rather mundane observation
      we made together involving a non-physiological transformed mast cell line as
      something that might be really interesting. I have never forgotten that lesson:
      Look at the data with an eye on the big picture. Sometimes the unexpected is more
      interesting than predicted results. His example in this regard was incredibly
      important when as an independent investigator a mistake in mouse sex
      determination led to unexpected and very confusing data. Yet, these data
      ultimately revealed a role for mast cells in male-specific protection in
      experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis.
      Bill's influence in immunology is far-reaching and will continue to be felt as
      those of us who train our own students and post-doctoral fellows pass on his
      wisdom and approach to scientific research.

PMID- 29593745
TI  - Integral Roles for Integrins in gammadelta T Cell Function.
AB  - Integrins are adhesion receptors on the cell surface that enable cells to respond
      to their environment. Most integrins are heterodimers, comprising alpha and beta
      type I transmembrane glycoprotein chains with large extracellular domains and
      short cytoplasmic tails. Integrins deliver signals through multiprotein complexes
      at the cell surface, which interact with cytoskeletal and signaling proteins to
      influence gene expression, cell proliferation, morphology, and migration.
      Integrin expression on gammadelta T cells (gammadeltaTc) has not been
      systematically investigated; however, reports in the literature dating back to
      the early 1990s reveal an understated role for integrins in gammadeltaTc
      function. Over the years, integrins have been investigated on resting and/or
      activated peripheral blood-derived polyclonal gammadeltaTc, gammadeltaTc clones,
      as well as gammadelta T intraepithelial lymphocytes. Differences in integrin
      expression have been found between alphabeta T cells (alphabetaTc) and
      gammadeltaTc, as well as between Vdelta1 and Vdelta2 gammadeltaTc. While most
      studies have focused on human gammadeltaTc, research has also been carried out in
      mouse and bovine models. Roles attributed to gammadeltaTc integrins include
      adhesion, signaling, activation, migration, tissue localization, tissue
      retention, cell spreading, cytokine secretion, tumor infiltration, and
      involvement in tumor cell killing. This review attempts to encompass all reports
      of integrins expressed on gammadeltaTc published prior to December 2017,
      highlights areas warranting further investigation, and discusses the relevance of
      integrin expression for gammadeltaTc function.

PMID- 29593746
TI  - Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage
      Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of
      Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5) In
      Vivo.
AB  - The invention of liver-humanized mouse models has made it possible to directly
      study the preerythrocytic stages of Plasmodium falciparum. In contrast, the
      current models to directly study blood stage infection in vivo are extremely
      limited. Humanization of the mouse blood stream is achievable by frequent
      injections of human red blood cells (hRBCs) and is currently the only system with
      which to study human malaria blood stage infections in a small animal model.
      Infections have been primarily achieved by direct injection of P. falciparum
      infected RBCs but as such, this modality of infection does not model the natural
      route of infection by mosquito bite and lacks the transition of parasites from
      liver stage infection to blood stage infection. Including these life cycle
      transition points in a small animal model is of relevance for testing therapeutic
      interventions. To this end, we used FRGN KO mice that were engrafted with human
      hepatocytes and performed a blood exchange under immune modulation to engraft the
      animals with more than 50% hRBCs. These mice were infected by mosquito bite with
      sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in
      noninvasively measurable liver stage burden by in vivo bioluminescent imaging
      (IVIS) at days 5-7 postinfection. Transition to blood stage infection was
      observed by IVIS from day 8 onward and then blood stage parasitemia increased
      with a kinetic similar to that observed in controlled human malaria infection. To
      assess the utility of this model, we tested whether a monoclonal antibody
      targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5
      (with known growth inhibitory activity in vitro) was capable of blocking blood
      stage infection in vivo when parasites emerge from the liver and found it highly
      effective. Together, these results show that a combined liver-humanized and blood
      humanized FRGN mouse model infected with luciferase-expressing P. falciparum will
      be a useful tool to study P. falciparum preerythrocytic and erythrocytic stages
      and enables the testing of interventions that target either one or both stages of
      parasite infection.

PMID- 29593747
TI  - Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides
      Containing CD8+ T Cell Epitopes.
AB  - Influenza peptide antigens coding for conserved T cell epitopes have the capacity
      to induce cross-protective influenza-specific immunity. Short peptide antigens
      used as a vaccine, however, often show poor immunogenicity. In this study, we
      demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for
      influenza peptide antigens, as shown by the induction of peptide-specific CD8+ T
      cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived
      GILGFVFTL peptide (GIL), formulated with WIV. By screening various concentrations
      of GIL and WIV, we found that both components contributed to the GIL-specific T
      cell response. Whereas co-localization of the peptide antigen and WIV adjuvant
      was found to be important, neither physical association between peptide and WIV
      nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We
      furthermore show that WIV may adjuvate T cell responses to a variety of peptides,
      using pools of either conserved wild-type influenza peptides or chemically
      altered peptide ligands. This study shows the potential of WIV as an adjuvant for
      influenza peptides. The simple formulation process and the solid safety record of
      WIV make this an attractive adjuvant for T cell peptides, and may also be used
      for non-influenza antigens.

PMID- 29593748
TI  - High-Mobility Group Nucleosome-Binding Protein 1 as Endogenous Ligand Induces
      Innate Immune Tolerance in a TLR4-Sirtuin-1 Dependent Manner in Human Blood
      Peripheral Mononuclear Cells.
AB  - High-mobility group nucleosome-binding protein 1 (HMGN1) functions as a non
      histone chromatin-binding protein in the cell nucleus. However, extracellular
      HMGN1 acts as an endogenous danger-associated inflammatory mediator (also called
      alarmin). We demonstrated that HMGN1 not only directly stimulated cytokine
      production but also had the capacity to induce immune tolerance by a TLR4
      dependent pathway, similar to lipopolysaccharide (LPS)-induced tolerance. HMGN1
      induced tolerance was accompanied by a metabolic shift associated with the
      inhibition of the induction of Warburg effect (aerobic glycolysis) and histone
      deacetylation via Sirtuin-1. In addition, HMGN1 pre-challenge of mice also
      downregulated TNF production similar to LPS-induced tolerance in vivo. In
      conclusion, HMGN1 is an endogenous TLR4 ligand that can induce both acute
      stimulation of cytokine production and long-term tolerance, and thus it might
      play a modulatory role in sterile inflammatory processes such as those induced by
      infection, trauma, or ischemia.

PMID- 29593750
TI  - The Domestication of the Amazon Tree Grape (Pourouma cecropiifolia) Under an
      Ecological Lens.
AB  - Domestication studies traditionally focus on the differences in morphological
      characteristics between wild and domesticated populations that are under direct
      selection, the components of the domestication syndrome. Here, we consider that
      other aspects can be modified, because of the interdependence between plant
      characteristics and the forces of natural selection. We investigated the ongoing
      domestication of Pourouma cecropiifolia populations cultivated by the Ticuna
      people in Western Amazonia, using traditional and ecological approaches. We
      compared fruit characteristics between wild and domesticated populations to
      quantify the direct effects of domestication. To examine the characteristics that
      are not under direct selection and the correlated effects of human selection and
      natural selection, we investigated the differences in vegetative characteristics,
      changes in seed:fruit allometric relations and the relations of these
      characteristics with variation in environmental conditions summarized in a
      principal component analysis. Domestication generated great changes in fruit
      characteristics, as expected in fruit crops. The fruits of domesticated plants
      had 20* greater mass and twice as much edible pulp as wild fruits. The plant
      height:DBH ratio and wood density were, respectively, 42% and 22% smaller in
      domesticated populations, probably in response to greater luminosity and higher
      sand content of the cultivated landscapes. Seed:fruit allometry was modified by
      domestication: although domesticated plants have heavier seeds, the domesticated
      fruits have proportionally (46%) smaller seed mass compared to wild fruits. The
      high light availability and poor soils of cultivated landscapes may have
      contributed to seed mass reduction, while human selection promoted seed mass
      increase in correlation with fruit mass increase. These contrasting effects
      generated a proportionately smaller increase in seed mass in domesticated plants.
      In this study, it was not possible to clearly dissociate the environmental
      effects from the domestication effects in changes in morphological
      characteristics, because the environmental conditions were intensively modified
      by human management, showing that plant domestication is intrinsically related to
      landscape domestication. Our results suggest that evaluation of environmental
      conditions together with human selection on domesticated phenotypes provide a
      better understanding of the changes generated by domestication in plants.

PMID- 29593749
TI  - Alternative Splicing of FOXP3-Virtue and Vice.
AB  - FOXP3 is the lineage-defining transcription factor of CD4+ CD25+ regulatory T
      cells. While many aspects of its regulation, interaction, and function are
      conserved among species, alternatively spliced FOXP3 isoforms are expressed only
      in human cells. This review summarizes current knowledge about alternative
      splicing of FOXP3 and the specific functions of FOXP3 isoforms in health and
      disease. Future perspectives in research and the therapeutic potential of
      manipulating alternative splicing of FOXP3 are discussed.

PMID- 29593751
TI  - Humic Substances: Determining Potential Molecular Regulatory Processes in Plants.
AB  - Humic substances (HSs) have considerable effects on soil fertility and crop
      productivity owing to their unique physiochemical and biochemical properties, and
      play a vital role in establishing biotic and abiotic interactions within the
      plant rhizosphere. A comprehensive understanding of the mode of action and tissue
      distribution of HS is, however, required, as this knowledge could be useful for
      devising advanced rhizospheric management practices. These substances trigger
      various molecular processes in plant cells, and can strengthen the plant's
      tolerance to various kinds of abiotic stresses. HS manifest their effects in
      cells through genetic, post-transcriptional, and post-translational modifications
      of signaling entities that trigger different molecular, biochemical, and
      physiological processes. Understanding of such fundamental mechanisms will
      provide a better perspective for defining the cues and signaling crosstalk of HS
      that mediate various metabolic and hormonal networks operating in plant systems.
      Various regulatory activities and distribution strategies of HS have been
      discussed in this review.

PMID- 29593752
TI  - Genetic Dissection of End-Use Quality Traits in Adapted Soft White Winter Wheat.
AB  - Soft white wheat is used in domestic and foreign markets for various end products
      requiring specific quality profiles. Phenotyping for end-use quality traits can
      be costly, time-consuming and destructive in nature, so it is advantageous to use
      molecular markers to select experimental lines with superior traits. An
      association mapping panel of 469 soft white winter wheat cultivars and advanced
      generation breeding lines was developed from regional breeding programs in the
      U.S. Pacific Northwest. This panel was genotyped on a wheat-specific 90 K iSelect
      single nucleotide polymorphism (SNP) chip. A total of 15,229 high quality SNPs
      were selected and combined with best linear unbiased predictions (BLUPs) from
      historical phenotypic data of the genotypes in the panel. Genome-wide association
      mapping was conducted using the Fixed and random model Circulating Probability
      Unification (FarmCPU). A total of 105 significant marker-trait associations were
      detected across 19 chromosomes. Potentially new loci for total flour yield,
      lactic acid solvent retention capacity, flour sodium dodecyl sulfate
      sedimentation and flour swelling volume were also detected. Better understanding
      of the genetic factors impacting end-use quality enable breeders to more
      effectively discard poor quality germplasm and increase frequencies of favorable
      end-use quality alleles in their breeding populations.

PMID- 29593753
TI  - Ethylene-Related Gene Expression Networks in Wood Formation.
AB  - Thickening of tree stems is the result of secondary growth, accomplished by the
      meristematic activity of the vascular cambium. Secondary growth of the stem
      entails developmental cascades resulting in the formation of secondary phloem
      outwards and secondary xylem (i.e., wood) inwards of the stem. Signaling and
      transcriptional reprogramming by the phytohormone ethylene modifies cambial
      growth and cell differentiation, but the molecular link between ethylene and
      secondary growth remains unknown. We addressed this shortcoming by analyzing
      expression profiles and co-expression networks of ethylene pathway genes using
      the AspWood transcriptome database which covers all stages of secondary growth in
      aspen (Populus tremula) stems. ACC synthase expression suggests that the ethylene
      precursor 1-aminocyclopropane-1-carboxylic acid (ACC) is synthesized during xylem
      expansion and xylem cell maturation. Ethylene-mediated transcriptional
      reprogramming occurs during all stages of secondary growth, as deduced from
      AspWood expression profiles of ethylene-responsive genes. A network centrality
      analysis of the AspWood dataset identified EIN3D and 11 ERFs as hubs. No overlap
      was found between the co-expressed genes of the EIN3 and ERF hubs, suggesting
      target diversification and hence independent roles for these transcription factor
      families during normal wood formation. The EIN3D hub was part of a large co
      expression gene module, which contained 16 transcription factors, among them
      several new candidates that have not been earlier connected to wood formation and
      a VND-INTERACTING 2 (VNI2) homolog. We experimentally demonstrated Populus EIN3D
      function in ethylene signaling in Arabidopsis thaliana. The ERF hubs ERF118 and
      ERF119 were connected on the basis of their expression pattern and gene co
      expression module composition to xylem cell expansion and secondary cell wall
      formation, respectively. We hereby establish data resources for ethylene
      responsive genes and potential targets for EIN3D and ERF transcription factors in
      Populus stem tissues, which can help to understand the range of ethylene targeted
      biological processes during secondary growth.

PMID- 29593754
TI  - Magnesium Transporter MGT6 Plays an Essential Role in Maintaining Magnesium
      Homeostasis and Regulating High Magnesium Tolerance in Arabidopsis.
AB  - Magnesium (Mg) is one of the essential nutrients for all living organisms. Plants
      acquire Mg from the environment and distribute within their bodies in the ionic
      form via Mg2+-permeable transporters. In Arabidopsis, the plasma membrane
      localized magnesium transporter MGT6 mediates Mg2+ uptake under Mg-limited
      conditions, and therefore is important for the plant adaptation to low-Mg
      environment. In this study, we further assessed the physiological function of
      MGT6 using a knockout T-DNA insertional mutant allele. We found that MGT6 was
      required for normal plant growth during various developmental stages when the
      environmental Mg2+ was low. Interestingly, in addition to the hypersensitivity to
      Mg2+ limitation, mgt6 mutants displayed dramatic growth defects when external
      Mg2+ was in excess. Compared with wild-type plants, mgt6 mutants generally
      contained less Mg2+ under both low and high external Mg2+ conditions. Reciprocal
      grafting experiments further underpinned a role of MGT6 in a shoot-based
      mechanism for detoxifying excessive Mg2+ in the environment. Moreover, we found
      that mgt6 mgt7 double mutant showed more severe phenotypes compared with single
      mutants under both low- and high-Mg2+ stress conditions, suggesting that these
      two MGT-type transporters play an additive role in controlling plant Mg2+
      homeostasis under a wide range of external Mg2+ concentrations.

PMID- 29593756
TI  - Genetics, Host Range, and Molecular and Pathogenic Characterization of
      Verticillium dahliae From Sunflower Reveal Two Differentiated Groups in Europe.
AB  - Verticillium wilt and leaf mottle of sunflower, caused by the fungus Verticillium
      dahliae (Vd) has become a major constraint to sunflower oil production in
      temperate European countries. Information about Vd from sunflower is very scarce
      despite genetics, molecular traits and pathogenic abilities of fungal strains
      affecting many other crops being widely known. Understanding and characterizing
      the diversity of Vd populations in those countries where sunflowers are frequent
      and severely affected by the fungus are essential for efficient breeding for
      resistance. In this study, we have analyzed genetic, molecular and pathogenic
      traits of Vd isolates affecting sunflower in European countries. When their
      genetics was investigated, almost all the isolates from France, Italy, Spain,
      Argentina, and Ukraine were assigned to vegetative compatibility group (VCG) 2B.
      In Bulgaria, Turkey, Romania, and Ukraine, some isolates were assigned to VCG6,
      but some others could not be assigned to any VCG. Genotyping markers used for Vd
      affecting crops other than sunflower showed that all the isolates were
      molecularly identified as race 2 and that markers of defoliating (D) and non
      defoliating (ND) pathotypes distinguished two well-differentiated clusters, one
      (E) grouping those isolates from Eastern Europe and the other (W) all those from
      the Western Europe and Argentina. All the isolates in cluster W were VCG2B, while
      the isolates in cluster E belonged to an unknown VCG or to VCG6. When the host
      range was investigated in the greenhouse, the fungus was highly pathogenic to
      artichoke, showing the importance of farming alternatives in the management of
      Verticillium attacks. Sunflower genotypes were inoculated with a selection of
      isolates in two experiments. Two groups were identified, one including the
      isolates from Western Europe, Argentina, and Ukraine, and the other including
      isolates from Bulgaria, Romania, and Turkey. Three pathogenic races were
      differentiated: V1, V2-EE (Eastern Europe) and V2-WE (Western Europe). Similarly,
      three differentials are proposed for race identification: HA 458 (universal
      susceptible), HA 89 (resistant to V2-EE, susceptible to V2-WE) and INRA2603
      (susceptible to V2-EE, resistant to V2-WE). The diversity found in Vd affecting
      sunflower must be taken into account in the search for resistance to the pathogen
      for European environments of sunflower production.

PMID- 29593755
TI  - Candidate DNA Barcode Tags Combined With High Resolution Melting (Bar-HRM) Curve
      Analysis for Authentication of Senna alexandrina Mill. With Validation in Crude
      Drugs.
AB  - Senna alexandrina (Fabaceae) is a globally recognized medicinal plant for its
      laxative properties as well as the only source of sennosides, and is highly
      exported bulk herb from India. Its major procurement is exclusively from limited
      cultivation, which leads to risks of deliberate or unintended adulteration. The
      market raw materials are in powdered or finished product form, which lead to
      difficulties in authentication. Here, DNA barcode tags based on chloroplast genes
      (rbcL and matK) and intergenic spacers (psbA-trnH and ITS) were developed for S.
      alexandrina along with the allied species. The ability and performance of the
      ITS1 region to discriminate among the Senna species resulted in the present
      proposal of the ITS1 tags as successful barcode. Further, these tags were coupled
      with high-resolution melting (HRM) curve analysis in a real-time PCR genotyping
      method to derive Bar-HRM (Barcoding-HRM) assays. Suitable HRM primer sets were
      designed through SNP detection and mutation scanning in genomic signatures of
      Senna species. The melting profiles of S. alexandrina and S. italica subsp.
      micrantha were almost identical and the remaining five species were clearly
      separated so that they can be differentiated by HRM method. The sensitivity of
      the method was utilized to authenticate market samples [Herbal Sample Assays
      (HSAs)]. HSA01 (S. alexandrina crude drug sample from Bangalore) and HSA06 (S.
      alexandrina crude drug sample from Tuticorin, Tamil Nadu, India) were found to be
      highly contaminated with S. italica subsp. micrantha. Species admixture samples
      mixed in varying percentage was identified sensitively with detection of
      contamination as low as 1%. The melting profiles of PCR amplicons are clearly
      distinct, which enables the authentic differentiation of species by the HRM
      method. This study reveals that DNA barcoding coupled with HRM is an efficient
      molecular tool to authenticate Senna herbal products in the market for quality
      control in the drug supply chain. CIMAP Communication Number: CIMAP/PUB/2017/31.

PMID- 29593757
TI  - Silencing of the Mitogen-Activated Protein Kinases (MAPK) Fus3 and Slt2 in
      Pseudocercospora fijiensis Reduces Growth and Virulence on Host Plants.
AB  - Pseudocercospora fijiensis, causal agent of the black Sigatoka disease (BSD) of
      Musa spp., has spread globally since its discovery in Fiji 1963 to all the banana
      and plantain growing areas across the globe. It is becoming the most damaging and
      economically important disease of this crop. The identification and
      characterization of genes that regulate infection processes and pathogenicity in
      P. fijiensis will provide important knowledge for the development of disease
      resistant cultivars. In many fungal plant pathogens, the Fus3 and Slt2 are
      reported to be essential for pathogenicity. Fus3 regulates filamentous-invasion
      pathways including the formation of infection structures, sporulation, virulence,
      and invasive and filamentous growth, whereas Slt2 is involved in the cell-wall
      integrity pathway, virulence, invasive growth, and colonization in host tissues.
      Here, we used RNAi-mediated gene silencing to investigate the role of the Slt2
      and Fus3 homologs in P. fijiensis in pathogen invasiveness, growth and
      pathogenicity. The PfSlt2 and PfFus3 silenced P. fijiensis transformants showed
      significantly lower gene expression and reduced virulence, invasive growth, and
      lower biomass in infected leaf tissues of East African Highland Banana (EAHB).
      This study suggests that Slt2 and Fus3 MAPK signaling pathways play important
      roles in plant infection and pathogenic growth of fungal pathogens. The silencing
      of these vital fungal genes through host-induced gene silencing (HIG) could be an
      alternative strategy for developing transgenic banana and plantain resistant to
      BSD.

PMID- 29593758
TI  - The Soybean Purple Acid Phosphatase GmPAP14 Predominantly Enhances External
      Phytate Utilization in Plants.
AB  - Induction and secretion of acid phosphatases (APases) is considered to be an
      important strategy for improving plant growth under conditions of low inorganic
      phosphate (Pi). Purple acid phosphatases (PAPs), are an important class of plant
      APases that could be secreted into the rhizosphere to utilize organic phosphorus
      (Po) for plant growth and development. To date, only a few members of the PAP
      family have been identified in soybean. In this paper, we identified a secreted
      PAP in soybean, GmPAP14, and investigated its role in utilizing external phytate,
      the main form of organic phosphorus in the soil. An analysis of its expression
      and promoter showed that GmPAP14 was mainly expressed in the root and was
      strongly induced following Po treatment, during which its expression expanded
      from meristematic to maturation zones and root hairs. In vitro enzyme assays
      indicated that GmPAP14 had a relatively high phytase activity. Furthermore,
      GmPAP14 overexpression increased secreted APase activities and phytase
      activities, leading to the improved use of external plant phytate, higher
      phosphorus content, and increased shoot weight. Thus, these results confirmed
      that GmPAP14 is an important gene induced in response to Po, and that it
      predominantly participates in utilizing external Po to enhance plant growth and
      development.

PMID- 29593759
TI  - Nutrient Characteristics in Relation to Plant Size of a Perennial Grass Under
      Grazing Exclusion in Degraded Grassland.
AB  - Identifying the linkages between nutrient properties and plant size is important
      for reducing uncertainty in understanding the mechanisms of plant phenotypic
      plasticity. Although the positive effects of grazing exclusion on plant
      morphological plasticity has been well documented, surprisingly little is known
      about the relationship of nutrient strategies with plant shoot size after long
      term grazing exclusion. We experimentally investigated the impacts of grazing
      exclusion over time (0, 9, 15, and 35 years) on the relationships of nutrient
      traits (nutrient concentration, allocation, and stoichiometry) of with
      morphological plasticity in Leymus chinensis, which is a dominant species in
      grasslands of Inner Mongolia, China. Our results showed that there was a
      significantly negative correlation between the degrees of plasticity and
      stability of various morphological traits. Increases in plant size by 126.41,
      164.17, and 247.47% were observed with the increase of grazing exclusion time of
      9, 15, and 35 years, respectively. Plant size was negatively correlated with
      nitrogen (N) and phosphorus (P) concentrations, but was positively correlated
      with carbon (C) concentration. Biomass partitioning and leaf to stem ratios of
      nutrient concentrations contributed more than 95% of the changes in N, P, and C
      allocation in L. chinensis leaves and stems induced by grazing exclusions. Nine
      years' grazing exclusion rapidly changed the nutrient concentrations (averaged by
      -34.84%), leaf to stem nutrient allocations (averaged by -86.75%), and ecological
      stoichiometry (averaged by +46.54%) compared to free-grazing, whereas there was
      no significant trend of these nutrient traits across the 9, 15, and 35 years'
      grazing exclusion in L. chinensis individuals. Our findings suggest that with the
      increase of the duration of the grazing exclusion, time effects on plant
      performances gradually weakened both in plant morphological plasticity and
      nutrient properties. There is a significant negative effect between plant sizes
      and nutrient traits under long-term grazing exclusion.

PMID- 29593760
TI  - Nitric Oxide Enables Germination by a Four-Pronged Attack on ABA-Induced Seed
      Dormancy.
AB  - Nitric oxide (?NO) is known to attenuate dormancy and promote germination, a
      function that seemingly depends on crosstalk with the abscisic acid (ABA)
      signaling network. In the past 2 years, a number of independent studies have
      revealed that ?NO gates the ABA signaling network at multiple steps, ensuring
      redundant and effectively irreversible control of germination. Here we summarize
      the recent studies, and propose a model of the multiple functions of ?NO in seed
      dormancy.

PMID- 29593761
TI  - 14-3-3 Proteins in Plant Hormone Signaling: Doing Several Things at Once.
AB  - In this review we highlight the advances achieved in the investigation of the
      role of 14-3-3 proteins in hormone signaling, biosynthesis, and transport. 14-3-3
      proteins are a family of conserved molecules that target a number of protein
      clients through their ability to recognize well-defined phosphorylated motifs. As
      a result, they regulate several cellular processes, ranging from metabolism to
      transport, growth, development, and stress response. High-throughput proteomic
      data and two-hybrid screen demonstrate that 14-3-3 proteins physically interact
      with many protein clients involved in the biosynthesis or signaling pathways of
      the main plant hormones, while increasing functional evidence indicates that 14-3
      3-target interactions play pivotal regulatory roles. These advances provide a
      framework of our understanding of plant hormone action, suggesting that 14-3-3
      proteins act as hubs of a cellular web encompassing different signaling pathways,
      transducing and integrating diverse hormone signals in the regulation of
      physiological processes.

PMID- 29593762
TI  - Overexpression of the Maize Sulfite Oxidase Increases Sulfate and GSH Levels and
      Enhances Drought Tolerance in Transgenic Tobacco.
AB  - Sulfite oxidase (SO) plays a pivotal role in sulfite metabolism. In our previous
      study, sulfite-oxidizing function of the SO from Zea mays (ZmSO) was
      characterized. To date, the knowledge of ZmSO's involvement in abiotic stress
      response is scarce. In this study, we aimed to investigate the role of ZmSO in
      drought stress. The transcript levels of ZmSO were relatively high in leaves and
      immature embryos of maize plants, and were up-regulated markedly by PEG-induced
      water stress. Overexpression of ZmSO improved drought tolerance in tobacco. ZmSO
      overexpressing transgenic plants showed higher sulfate and glutathione (GSH)
      levels but lower hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents
      under drought stress, indicating that ZmSO confers drought tolerance by enhancing
      GSH-dependent antioxidant system that scavenged ROS and reduced membrane injury.
      In addition, the transgenic plants exhibited more increased stomatal response
      than the wild-type (WT) to water deficit. Interestingly, application of exogenous
      GSH effectively alleviated growth inhibition in both WT and transgenic plants
      under drought conditions. qPCR analysis revealed that the expression of several
      sulfur metabolism-related genes was significantly elevated in the ZmSO
      overexpressing lines. Taken together, these results imply that ZmSO confers
      enhanced drought tolerance in transgenic tobacco plants possibly through
      affecting stomatal regulation, GSH-dependent antioxidant system, and sulfur
      metabolism-related gene expression. ZmSO could be exploited for developing
      drought-tolerant maize varieties in molecular breeding.

PMID- 29593763
TI  - Identification and Expression Analysis of Medicago truncatula Isopentenyl
      Transferase Genes (IPTs) Involved in Local and Systemic Control of Nodulation.
AB  - Cytokinins are essential for legume plants to establish a nitrogen-fixing
      symbiosis with rhizobia. Recently, the expression level of cytokinin biosynthesis
      IPTs (ISOPENTENYLTRANSFERASES) genes was shown to be increased in response to
      rhizobial inoculation in Lotus japonicus, Medicago truncatula and Pisum sativum.
      In addition to its well-established positive role in nodule primordium initiation
      in root cortex, cytokinin negatively regulates infection processes in the
      epidermis. Moreover, it was reported that shoot-derived cytokinin inhibits the
      subsequent nodule formation through AON (autoregulation of nodulation) pathway.
      In L. japonicus, LjIPT3 gene was shown to be activated in the shoot phloem via
      the components of AON system, negatively affecting nodulation. However, in M.
      truncatula, the detailed analysis of MtIPTs expression, both in roots and shoots,
      in response to nodulation has not been performed yet, and the link between IPTs
      and AON has not been studied so far. In this study, we performed an extensive
      analysis of MtIPTs expression levels in different organs, focusing on the
      possible role of MtIPTs in nodule development. MtIPTs expression dynamics in
      inoculated roots suggest that besides its early established role in the nodule
      primordia development, cytokinin may be also important for later stages of
      nodulation. According to expression analysis, MtIPT3, MtIPT4, and MtIPT5 are
      activated in the shoots in response to inoculation. Among these genes, MtIPT3 is
      the only one the induction of which was not observed in leaves of the sunn-3
      mutant defective in CLV1-like kinase, the key component of AON, suggesting that
      MtIPT3 is activated in the shoots in an AON-dependent manner. Taken together, our
      findings suggest that MtIPTs are involved in the nodule development at different
      stages, both locally in inoculated roots and systemically in shoots, where their
      expression can be activated in an AON-dependent manner.

PMID- 29593764
TI  - Genetic Dissection and Simultaneous Improvement of Drought and Low Nitrogen
      Tolerances by Designed QTL Pyramiding in Rice.
AB  - Drought and low nitrogen are the most common abiotic stresses limiting rice
      productivity in the rainfed rice areas of Asia and Africa. Development and
      adoption of green super rice (GSR) varieties with greatly improved drought
      tolerance (DT) and low nitrogen tolerance (LNT) are the most efficient way to
      resolve this problem. In this study, using three sets of trait-specific
      introgression lines (ILs) in a Xian (indica) variety Huanghuazhan (HHZ)
      background, we identified nine DT-QTL and seven LNT-QTL by a segregation
      distortion approach and a genome-wide association study, respectively. Based on
      performances of DT and LNT and genotypes at the detected QTL, two ILs M79 and
      M387 with DT and LNT were selected for cross-making to validate the identified
      QTL and to develop DT and LNT rice lines by pyramiding two DT-QTL (qDT3.9 and
      qDT6.3) and two LNT-QTL (qGY1 and qSF8). Using four pairs of kompetitive allele
      specific PCR (KASP) SNP markers, we selected 66 F2 individuals with different
      combinations of the target DT- and LNT-QTL favorable alleles and they showed
      expected improvement in DT and/or LNT, which were further validated by the
      significant improvement in DT and/or LNT of their F3 progeny testing. Based on
      evaluation of pyramiding lines in F3 lines under drought, low nitrogen (LN) and
      normal conditions, four promising pyramiding lines having different QTL favorable
      alleles were selected, which showed significantly improved tolerances to drought
      and/or LN than HHZ and their IL parents. Our results demonstrated that trait
      specific ILs could effectively connect QTL mapping and QTL pyramiding breeding,
      and designed QTL pyramiding (DQP) using ILs could be more effective in molecular
      rice breeding for complex quantitative traits.

PMID- 29593765
TI  - Zinc and Iron Concentration as Affected by Nitrogen Fertilization and Their
      Localization in Wheat Grain.
AB  - Nearly half of the world cereal production comes from soils low or marginal in
      plant available zinc, leading to unsustainable and poor quality grain production.
      Therefore, the effects of nitrogen (N) rate and application time on zinc (Zn) and
      iron (Fe) concentration in wheat grain were investigated. Wheat (Triticum
      aestivum var. Krabat) was grown in a growth chamber with 8 and 16 h of day and
      night periods, respectively. The N rates were 29, 43, and 57 mg N kg-1 soil,
      equivalent to 80, 120, and 160 kg N ha-1. Zinc and Fe were applied at 10 mg kg-1
      growth media. In one of the N treatments, additional Zn and Fe through foliar
      spray (6 mg of Zn or Fe in 10 ml water/pot) was applied. Micro-analytical
      localization of Zn and Fe within grain was performed using scanning macro-X-ray
      fluorescence (MA-XRF) and laser ablation-inductively coupled plasma-mass
      spectrometry (LA-ICP-MS). The following data were obtained: grain and straw yield
      pot-1, 1000 grains weight, number of grains pot-1, whole grain protein content,
      concentration of Zn and Fe in the grains. Grain yield increased from 80 to 120 kg
      N ha-1 rates only and decreased at 160 kg N ha-1 g. Relatively higher protein
      content and Zn and Fe concentration in the grain were recorded with the split N
      application of 160 kg N ha-1. Soil and foliar supply of Zn and Fe (Zn + Fes+f),
      with a single application of 120 kg N ha-1N at sowing, increased the
      concentration of Zn by 46% and of Fe by 35%, as compared to their growth media
      application only. Line scans of freshly cut areas of sliced grains showed co
      localization of Zn and Fe within germ, crease and aleurone. We thus conclude that
      split application of N at 160 kg ha-1 at sowing and stem elongation, in
      combination with soil and foliar application of Zn and Fe, can be a good
      agricultural practice to enhance protein content and the Zn and Fe concentration
      in grain.

PMID- 29593766
TI  - Overexpression of OsNAC14 Improves Drought Tolerance in Rice.
AB  - Plants have evolved to have sophisticated adaptation mechanisms to cope with
      drought stress by reprograming transcriptional networks through drought
      responsive transcription factors. NAM, ATAF1-2, and CUC2 (NAC) transcription
      factors are known to be associated with various developmental processes and
      stress tolerance. In this study, we functionally characterized the rice drought
      responsive transcription factor OsNAC14. OsNAC14 was predominantly expressed at
      meiosis stage but is induced by drought, high salinity, ABA, and low temperature
      in leaves. Overexpression of OsNAC14 resulted in drought tolerance at the
      vegetative stage of growth. Field drought tests demonstrated that OsNAC14
      overexpressing transgenic rice lines exhibited higher number of panicle and
      filling rate compared to non-transgenic plants under drought conditions. RNA
      sequencing analysis revealed that OsNAC14 overexpression elevated the expression
      of genes for stress response, DNA damage repair, defense related, and
      strigolactone biosynthesis. In addition, chromatin immunoprecipitation analysis
      confirmed the direct interaction of OsNAC14 with the promoter of OsRAD51A1, a key
      component in homologous recombination in DNA repair system. Collectively, these
      results indicate that OsNAC14 mediates drought tolerance by recruiting factors
      involved in DNA damage repair and defense response resulting in improved
      tolerance to drought.

PMID- 29593767
TI  - mRNA Decapping and 5'-3' Decay Contribute to the Regulation of ABA Signaling in
      Arabidopsis thaliana.
AB  - Defects in RNA processing and degradation pathways often lead to developmental
      abnormalities, impaired hormonal signaling and altered resistance to abiotic and
      biotic stress. Here we report that components of the 5'-3' mRNA decay pathway,
      DCP5, LSM1-7 and XRN4, contribute to a proper response to a key plant hormone
      abscisc acid (ABA), albeit in a different manner. Plants lacking DCP5 are more
      sensitive to ABA during germination, whereas lsm1a lsm1b and xrn4-5 mutants are
      affected at the early stages of vegetative growth. In addition, we show that DCP5
      and LSM1 regulate mRNA stability and act in translational repression of the main
      components of the early ABA signaling, PYR/PYL ABA receptors and SnRK2s protein
      kinases. mRNA decapping DCP and LSM1-7 complexes also appear to modulate ABA
      dependent expression of stress related transcription factors from the
      AP2/ERF/DREB family that in turn affect the level of genes regulated by the
      PYL/PYR/RCAR-PP2C-SnRK2 pathway. These observations suggest that ABA signaling
      through PYL/PYR/RCAR receptors and SnRK2s kinases is regulated directly and
      indirectly by the cytoplasmic mRNA decay pathway.

PMID- 29593768
TI  - Genetic and Molecular Mechanisms Underlying Symbiotic Specificity in Legume
      Rhizobium Interactions.
AB  - Legumes are able to form a symbiotic relationship with nitrogen-fixing soil
      bacteria called rhizobia. The result of this symbiosis is to form nodules on the
      plant root, within which the bacteria can convert atmospheric nitrogen into
      ammonia that can be used by the plant. Establishment of a successful symbiosis
      requires the two symbiotic partners to be compatible with each other throughout
      the process of symbiotic development. However, incompatibility frequently occurs,
      such that a bacterial strain is unable to nodulate a particular host plant or
      forms nodules that are incapable of fixing nitrogen. Genetic and molecular
      mechanisms that regulate symbiotic specificity are diverse, involving a wide
      range of host and bacterial genes/signals with various modes of action. In this
      review, we will provide an update on our current knowledge of how the recognition
      specificity has evolved in the context of symbiosis signaling and plant immunity.

PMID- 29593769
TI  - Genetic Loci Conferring Reducing Sugar Accumulation and Conversion of Cold-Stored
      Potato Tubers Revealed by QTL Analysis in a Diploid Population.
AB  - Cold-induced sweetening (CIS) caused by reducing sugar (RS) accumulation during
      storage in low temperature in potato tubers is a critical factor influencing the
      quality of fried potato products. The reconditioning (REC) by arising storage
      temperature is a common measure to lower down RS. However, both CIS and REC are
      genotype-dependent and the genetic basis remains uncertain. In the present study,
      with a diploid potato population with broad genetic background, four reproducible
      QTL of CIS and two of REC were resolved on chromosomes 5, 6, and 7 of the CIS
      sensitive parent and chromosomes 5 and 11 of the CIS-resistant parent,
      respectively, implying that these two traits may be genetically independent. This
      hypothesis was also supported by the colocalization of two functional genes, a
      starch synthesis gene AGPS2 mapped in QTL CIS_E_07-1 and a starch hydrolysis gene
      GWD colocated with QTL REC_B_05-1. The cumulative effects of identified QTL were
      proved to contribute largely and stably to CIS and REC and confirmed with a
      natural population composed of a range of cultivars and breeding lines. The
      present research identified reproducible QTL for CIS and REC of potato in diverse
      conditions and elucidated for the first time their cumulative genetic effects,
      which provides theoretical bases and applicable means for tuber quality
      improvement.

PMID- 29593771
TI  - Checkmite!? Is the Resistance to Phytophagous Mites on Short and Stocky Wild
      Oryza Species?

PMID- 29593770
TI  - The Glycerate and Phosphorylated Pathways of Serine Synthesis in Plants: The
      Branches of Plant Glycolysis Linking Carbon and Nitrogen Metabolism.
AB  - Serine metabolism in plants has been studied mostly in relation to
      photorespiration where serine is formed from two molecules of glycine. However,
      two other pathways of serine formation operate in plants and represent the
      branches of glycolysis diverging at the level of 3-phosphoglyceric acid. One
      branch (the glycerate - serine pathway) is initiated in the cytosol and involves
      glycerate formation from 3-phosphoglycerate, while the other (the phosphorylated
      serine pathway) operates in plastids and forms phosphohydroxypyruvate as an
      intermediate. Serine formed in these pathways becomes a precursor of glycine,
      formate and glycolate accumulating in stress conditions. The pathways can be
      linked to GABA shunt via transamination reactions and via participation of the
      same reductase for both glyoxylate and succinic semialdehyde. In this review
      paper we present a hypothesis of the regulation of redox balance in stressed
      plant cells via participation of the reactions associated with glycerate and
      phosphorylated serine pathways. We consider these pathways as important processes
      linking carbon and nitrogen metabolism and maintaining cellular redox and energy
      levels in stress conditions.

PMID- 29593772
TI  - Genetic and Developmental Basis for Increased Leaf Thickness in the Arabidopsis
      Cvi Ecotype.
AB  - Leaf thickness is a quantitative trait that is associated with the ability of
      plants to occupy dry, high irradiance environments. Despite its importance, leaf
      thickness has been difficult to measure reproducibly, which has impeded progress
      in understanding its genetic basis, and the associated anatomical mechanisms that
      pattern it. Here, we used a custom-built dual confocal profilometer device to
      measure leaf thickness in the Arabidopsis Ler * Cvi recombinant inbred line
      population and found statistical support for four quantitative trait loci (QTL)
      associated with this trait. We used publically available data for a suite of
      traits relating to flowering time and growth responses to light quality and show
      that three of the four leaf thickness QTL coincide with QTL for at least one of
      these traits. Using time course photography, we quantified the relative growth
      rate and the pace of rosette leaf initiation in the Ler and Cvi ecotypes. We
      found that Cvi rosettes grow slower than Ler, both in terms of the rate of leaf
      initiation and the overall rate of biomass accumulation. Collectively, these data
      suggest that leaf thickness is tightly linked with physiological status and may
      present a tradeoff between the ability to withstand stress and rapid vegetative
      growth. To understand the anatomical basis of leaf thickness, we compared cross
      sections of Cvi and Ler leaves and show that Cvi palisade mesophyll cells
      elongate anisotropically contributing to leaf thickness. Flow cytometry of whole
      leaves show that endopolyploidy accompanies thicker leaves in Cvi. Overall, our
      data suggest that mechanistically, an altered schedule of cellular events
      affecting endopolyploidy and increasing palisade mesophyll cell length contribute
      to increase of leaf thickness in Cvi. Ultimately, knowledge of the genetic basis
      and developmental trajectory leaf thickness will inform the mechanisms by which
      natural selection acts to produce variation in this adaptive trait.

PMID- 29593773
TI  - Sequencing and Analysis of Strobilanthes cusia (Nees) Kuntze Chloroplast Genome
      Revealed the Rare Simultaneous Contraction and Expansion of the Inverted Repeat
      Region in Angiosperm.
AB  - Ban-Lan-Gen, the root tissues derived from several morphologically
      indistinguishable plant species, have been used widely in traditional Chinese
      medicines for numerous years. The identification of reliable markers to
      distinguish various source plant species is critical for the effective and safe
      use of products containing Ban-Lan-Gen. Here, we analyzed and characterized the
      complete chloroplast (cp) genome sequence of Strobilanthes cusia (Nees) Kuntze to
      identify high-resolution markers for the species determination of Southern Ban
      Lan-Gen. Total DNA was extracted and subjected to next-generation sequencing. The
      cp genome was then assembled, and the gaps were filled using PCR amplification
      and Sanger sequencing. Genome annotation was conducted using CpGAVAS web server.
      The genome was 144,133 bp in length, presenting a typical quadripartite structure
      of large (LSC; 91,666 bp) and small (SSC; 17,328 bp) single-copy regions
      separated by a pair of inverted repeats (IRs; 17,811 bp). The genome encodes 113
      unique genes, including 79 protein-coding, 30 transfer RNA, and 4 ribosomal RNA
      genes. A total of 20 tandem, 2 forward, and 6 palindromic repeats were detected
      in the genome. A phylogenetic analysis based on 65 protein-coding genes showed
      that S. cusia was closely related to Andrographis paniculata and Ruellia
      breedlovei, which belong to the same family, Acanthaceae. One interesting feature
      is that the IR regions apparently undergo simultaneous contraction and expansion,
      resulting in the presence of single copies of rps19, rpl2, rpl23, and ycf2 in the
      LSC region and the duplication of psbA and trnH genes in the IRs. This study
      provides the first complete cp genome in the genus Strobilanthes, containing
      critical information for the classification of various Strobilanthes species in
      the future. This study also provides the foundation for precisely determining the
      plant sources of Ban-Lan-Gen.

PMID- 29593774
TI  - The Role of Hydrogen Peroxide in Mediating the Mechanical Wounding-Induced
      Freezing Tolerance in Wheat.
AB  - Systemic wound response (SWR), a well-characterized systemic signaling response,
      plays crucial roles in plant defense responses. Progress in understanding of the
      SWR in abiotic stress has also been aided by the researchers. However, the
      function of SWR in freezing stress remains elusive. In this study, we showed that
      local mild mechanical wounding enhanced freezing tolerance in newly occurred
      systemic leaves of wheat plants (Triticum aestivum L.). Wounding significantly
      increased the maximal photochemical efficiency of photosystem II, net
      photosynthetic rate, and the activities of the antioxidant enzymes under freezing
      stress. Wounding also alleviated freezing-induced chlorophyll decomposition,
      electrolyte leakage, water lose, and membrane peroxidation. In addition, wounding
      induced freezing stress mitigation was closely associated with the ratio between
      reduced glutathione (GSH) and oxidized glutathione (GSSG), and the ratio between
      ascorbate (AsA) and dehydroascorbate (DHA), as well as the contents of total
      soluble sugars and free amino acids. Importantly, pharmacological study showed
      that wounding-induced freezing tolerance was substantially arrested by
      pretreatment of wheat leaves with the scavenger of hydrogen peroxide (H2O2) or
      the inhibitor of NADPH oxidase (RBOH). These results support the hypothesis that
      local mechanical wounding-induced SWR in newly occurred leaves is largely
      attributed to RBOH-dependent H2O2 production, which may subsequently induce
      freezing tolerance in wheat plants. This mechanism may have a potential
      application to reduce the yield losses of wheat under late spring freezing
      conditions. Highlights: In our previous research, we found that local mechanical
      wounding could induce freezing tolerance in the upper systemic leaves of wheat
      plants. Surprisingly, in this paper, we further demonstrated that local
      mechanical wounding could also increase freezing resistance in newly occurred
      leaves of wheat plants. RBOH mediated H2O2 and ascorbate-glutathione cycle
      participate in this systemic wound response.

PMID- 29593775
TI  - Evaluation of the Relationship between the Serum Alkaline Phosphatase Level at
      Dialysis Initiation and All-Cause Mortality: A Multicenter, Prospective Study.
AB  - Background/Aim: High serum alkaline phosphatase (ALP) levels predict mortality
      independent of bone metabolism parameters and liver function test results in
      patients on hemodialysis. The relationship between serum ALP at dialysis
      initiation and mortality during maintenance dialysis is unknown; therefore, we
      aimed to identify an association. Methods: This multicenter, prospective cohort
      study analyzed 1,213 patients registered in the Aichi Cohort Study of Prognosis
      in Patients Newly Initiated into Dialysis from October 2011 to September 2013.
      Patients were divided into 2 groups based on serum ALP levels. All-cause
      mortality and incidences of cardiovascular events after dialysis initiation were
      compared using the log-rank test and multivariate Cox proportional hazard
      regression analysis. We performed stratified analysis based on parathyroid
      hormone (PTH) levels. Results: During the follow-up, 109 (18.0%) and 86 (14.1%)
      patients died in the high ALP group (232 >=IU/L; High ALP group) and low ALP
      group (232 <IU/L; Low ALP group), respectively. All-cause mortality was
      significantly higher in the High ALP group than in the Low ALP group (p = 0.014).
      The serum ALP level was significantly correlated with the all-cause mortality
      rate (hazard ratio = 1.17 per 100 IU/L increase of ALP, 95% confidence interval:
      1.11-1.24, p < 0.001). The all-cause mortality rate was significantly higher in
      the High ALP group among patients with low (<150 pg/mL) or normal (150-300 pg/mL)
      PTH levels (p = 0.012 and p = 0.005, respectively) than in the Low ALP group;
      there was no significant difference among patients with a high (>=300 pg/mL) PTH
      level (p = 1.000). Conclusion: The serum ALP level at dialysis initiation is
      associated with all-cause mortality during maintenance dialysis.

PMID- 29593776
TI  - Navigating the Interface Between Landscape Genetics and Landscape Genomics.
AB  - As next-generation sequencing data become increasingly available for non-model
      organisms, a shift has occurred in the focus of studies of the geographic
      distribution of genetic variation. Whereas landscape genetics studies primarily
      focus on testing the effects of landscape variables on gene flow and genetic
      population structure, landscape genomics studies focus on detecting candidate
      genes under selection that indicate possible local adaptation. Navigating the
      transition between landscape genomics and landscape genetics can be challenging.
      The number of molecular markers analyzed has shifted from what used to be a few
      dozen loci to thousands of loci and even full genomes. Although genome scale data
      can be separated into sets of neutral loci for analyses of gene flow and
      population structure and putative loci under selection for inference of local
      adaptation, there are inherent differences in the questions that are addressed in
      the two study frameworks. We discuss these differences and their implications for
      study design, marker choice and downstream analysis methods. Similar to the rapid
      proliferation of analysis methods in the early development of landscape genetics,
      new analytical methods for detection of selection in landscape genomics studies
      are burgeoning. We focus on genome scan methods for detection of selection, and
      in particular, outlier differentiation methods and genetic-environment
      association tests because they are the most widely used. Use of genome scan
      methods requires an understanding of the potential mismatches between the biology
      of a species and assumptions inherent in analytical methods used, which can lead
      to high false positive rates of detected loci under selection. Key to choosing
      appropriate genome scan methods is an understanding of the underlying demographic
      structure of study populations, and such data can be obtained using neutral loci
      from the generated genome-wide data or prior knowledge of a species'
      phylogeographic history. To this end, we summarize recent simulation studies that
      test the power and accuracy of genome scan methods under a variety of demographic
      scenarios and sampling designs. We conclude with a discussion of additional
      considerations for future method development, and a summary of methods that show
      promise for landscape genomics studies but are not yet widely used.

PMID- 29593777
TI  - High-Throughput Sequencing Strategy for Microsatellite Genotyping Using
      Neotropical Fish as a Model.
AB  - Genetic diversity and population studies are essential for conservation and
      wildlife management programs. However, monitoring requires the analysis of
      multiple loci from many samples. These processes can be laborious and expensive.
      The choice of microsatellites and PCR calibration for genotyping are particularly
      daunting. Here we optimized a low-cost genotyping method using multiple
      microsatellite loci for simultaneous genotyping of up to 384 samples using next
      generation sequencing (NGS). We designed primers with adapters to the
      combinatorial barcoding amplicon library and sequenced samples by MiSeq. Next, we
      adapted a bioinformatics pipeline for genotyping microsatellites based on read
      length and sequence content. Using primer pairs for eight microsatellite loci
      from the fish Prochilodus costatus, we amplified, sequenced, and analyzed the DNA
      of 96, 288, or 384 individuals for allele detection. The most cost-effective
      methodology was a pseudo-multiplex reaction using a low-throughput kit of 1 M
      reads (Nano) for 384 DNA samples. We observed an average of 325 reads per
      individual per locus when genotyping eight loci. Assuming a minimum requirement
      of 10 reads per loci, two to four times more loci could be tested in each run,
      depending on the quality of the PCR reaction of each locus. In conclusion, we
      present a novel method for microsatellite genotyping using Illumina combinatorial
      barcoding that dispenses exhaustive PCR calibrations, since non-specific
      amplicons can be eliminated by bioinformatics analyses. This methodology rapidly
      provides genotyping data and is therefore a promising development for large-scale
      conservation-genetics studies.

PMID- 29593779
TI  - Genetic Diversity and Population Structure of F3:6 Nebraska Winter Wheat
      Genotypes Using Genotyping-By-Sequencing.
AB  - The availability of information on the genetic diversity and population structure
      in wheat (Triticum aestivum L.) breeding lines will help wheat breeders to better
      use their genetic resources and manage genetic variation in their breeding
      program. The recent advances in sequencing technology provide the opportunity to
      identify tens or hundreds of thousands of single nucleotide polymorphism (SNPs)
      in large genome species (e.g., wheat). These SNPs can be utilized for
      understanding genetic diversity and performing genome wide association studies
      (GWAS) for complex traits. In this study, the genetic diversity and population
      structure were investigated in a set of 230 genotypes (F3:6) derived from various
      crosses as a prerequisite for GWAS and genomic selection. Genotyping-by
      sequencing provided 25,566 high-quality SNPs. The polymorphism information
      content (PIC) across chromosomes ranged from 0.09 to 0.37 with an average of
      0.23. The distribution of SNPs markers on the 21 chromosomes ranged from 319 on
      chromosome 3D to 2,370 on chromosome 3B. The analysis of population structure
      revealed three subpopulations (G1, G2, and G3). Analysis of molecular variance
      identified 8% variance among and 92% within subpopulations. Of the three
      subpopulations, G2 had the highest level of genetic diversity based on three
      genetic diversity indices: Shannon's information index (I) = 0.494, diversity
      index (h) = 0.328 and unbiased diversity index (uh) = 0.331, while G3 had lowest
      level of genetic diversity (I = 0.348, h = 0.226 and uh = 0.236). This high
      genetic diversity identified among the subpopulations can be used to develop new
      wheat cultivars.

PMID- 29593778
TI  - Evaluation of Reference Genes to Analyze Gene Expression in Silverside
      Odontesthes humensis Under Different Environmental Conditions.
AB  - Some mammalian reference genes, which are widely used to normalize the qRT-PCR,
      could not be used for this purpose due to its high expression variation. The
      normalization with false reference genes leads to misinterpretation of results.
      The silversides (Odontesthes spp.) has been used as models for evolutionary,
      osmoregulatory and environmental pollution studies but, up to now, there are no
      studies about reference genes in any Odontesthes species. Furthermore, many
      studies on silversides have used reference genes without previous validations.
      Thus, present study aimed to was to clone and sequence potential reference genes,
      thereby identifying the best ones in Odontesthes humensis considering different
      tissues, ages and conditions. For this purpose, animals belonging to three ages
      (adults, juveniles, and immature) were exposed to control, Roundup(r), and
      seawater treatments for 24 h. Blood samples were subjected to flow-cytometry and
      other collected tissues to RNA extraction; cDNA synthesis; molecular cloning; DNA
      sequencing; and qRT-PCR. The candidate genes tested included 18s, actb, ef1a,
      eif3g, gapdh, h3a, atp1a, and tuba. Gene expression results were analyzed using
      five algorithms that ranked the candidate genes. The flow-cytometry data showed
      that the environmental challenges could trigger a systemic response in the
      treated fish. Even during this systemic physiological disorder, the consensus
      analysis of gene expression revealed h3a to be the most stable gene expression
      when only the treatments were considered. On the other hand, tuba was the least
      stable gene in the control and gapdh was the least stable in both Roundup(r) and
      seawater groups. In conclusion, the consensus analyses of different tissues,
      ages, and treatments groups revealed that h3a is the most stable gene whereas
      gapdh and tuba are the least stable genes, even being considered two constitutive
      genes.

PMID- 29593780
TI  - Accuracy of Genomic Evaluations of Juvenile Growth Rate in Common Carp (Cyprinus
      carpio) Using Genotyping by Sequencing.
AB  - Cyprinids are the most important group of farmed fish globally in terms of
      production volume, with common carp (Cyprinus carpio) being one of the most
      valuable species of the group. The use of modern selective breeding methods in
      carp is at a formative stage, implying a large scope for genetic improvement of
      key production traits. In the current study, a population of 1,425 carp
      juveniles, originating from a partial factorial cross between 40 sires and 20
      dams, was used for investigating the potential of genomic selection (GS) for
      juvenile growth, an exemplar polygenic production trait. RAD sequencing was used
      to identify and genotype SNP markers for subsequent parentage assignment,
      construction of a medium density genetic map (12,311 SNPs), genome-wide
      association study (GWAS), and testing of GS. A moderate heritability was
      estimated for body length of carp at 120 days (as a proxy of juvenile growth) of
      0.33 (s.e. 0.05). No genome-wide significant QTL was identified using a single
      marker GWAS approach. Genomic prediction of breeding values outperformed pedigree
      based prediction, resulting in 18% improvement in prediction accuracy. The impact
      of reduced SNP densities on prediction accuracy was tested by varying minor
      allele frequency (MAF) thresholds, with no drop in prediction accuracy until the
      MAF threshold is set <0.3 (2,744 SNPs). These results point to the potential for
      GS to improve economically important traits in common carp breeding programs.

PMID- 29593781
TI  - Incidentalome in Neurogenetics: Pathogenic Variant of NSD1 in a Patient With
      Spinocerebellar Ataxia (SCA).
AB  - Background: Genetic studies of late-onset sporadic ataxias (>40 years of age) are
      not routinely indicated. For unresolved cases, next-generation sequencing (NGS)
      tools, such as whole-exome sequencing (WES), are available for a definitive
      diagnosis. Case presentation: Our patient is a woman with a usual facial
      phenotype and anthropometry, who developed ataxia at 45 years of age, with no
      relevant family history and an initial clinical approach that ruled out common
      aetiologies. WES was performed when the patient was 54 years old. The results
      identified the heterozygous pathogenic variant c.248delA (p.N83MfsX4) in the
      nuclear receptor-binding SET domain protein 1 (NSD1; MIM 606681) gene (related to
      Sotos syndrome), which was not associated with ataxia and is not related to the
      patient's phenotype. Sanger sequencing of NSD1 in two different laboratories
      confirmed the variant. Conclusions: NGS findings generally offer valuable
      information that can be used for clinical decision-making. However, an incidental
      finding that leads to defining new clinical and bioethical actions is also
      possible. Consequently, the biological importance of this type of genetic
      "incidentalome" must be determined.

PMID- 29593782
TI  - Bilateral Transcranial Direct Current Stimulation Reshapes Resting-State Brain
      Networks: A Magnetoencephalography Assessment.
AB  - Transcranial direct current stimulation (tDCS) can noninvasively induce brain
      plasticity, and it is potentially useful to treat patients affected by
      neurological conditions. However, little is known about tDCS effects on resting
      state brain networks, which are largely involved in brain physiological functions
      and in diseases. In this randomized, sham-controlled, double-blind study on
      healthy subjects, we have assessed the effect of bilateral tDCS applied over the
      sensorimotor cortices on brain and network activity using a whole-head
      magnetoencephalography system. Bilateral tDCS, with the cathode (-) centered over
      C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal
      fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and
      gamma power and increases global connectivity, especially in delta, alpha, beta,
      and gamma frequencies. The increase of connectivity is consistent across bands
      and widespread. These results shed new light on the effects of tDCS and may be of
      help in personalizing treatments in neurological disorders.

PMID- 29593783
TI  - Perinatal Programming of Circadian Clock-Stress Crosstalk.
AB  - An intact communication between circadian clocks and the stress system is
      important for maintaining physiological homeostasis under resting conditions and
      in response to external stimuli. There is accumulating evidence for a reciprocal
      interaction between both-from the systemic to the molecular level. Disruption of
      this interaction by external factors such as shiftwork, jetlag, or chronic stress
      increases the risk of developing metabolic, immune, or mood disorders. From
      experiments in rodents, we know that both systems maturate during the perinatal
      period. During that time, exogenous factors such as stress or alterations in the
      external photoperiod may critically affect-or program-physiological functions
      later in life. This developmental programming process has been attributed to
      maternal stress signals reaching the embryo, which lastingly change gene
      expression through the induction of epigenetic mechanisms. Despite the well-known
      function of the adult circadian system in temporal coordination of physiology and
      behavior, the role of maternal and embryonic circadian clocks during pregnancy
      and postnatal development is still poorly defined. A better understanding of the
      circadian-stress crosstalk at different periods of development may help to
      improve stress resistance and devise preventive and therapeutic strategies
      against chronic stress-associated disorders.

PMID- 29593784
TI  - Precision Light for the Treatment of Psychiatric Disorders.
AB  - Circadian timekeeping can be reset by brief flashes of light using stimulation
      protocols thousands of times shorter than those previously assumed to be
      necessary for traditional phototherapy. These observations point to a future
      where flexible architectures of nanosecond-, microsecond-, and millisecond-scale
      light pulses are compiled to reprogram the brain's internal clock when it has
      been altered by psychiatric illness or advanced age. In the current review, we
      present a chronology of seminal experiments that established the synchronizing
      influence of light on the human circadian system and the efficacy of prolonged
      bright-light exposure for reducing symptoms associated with seasonal affective
      disorder. We conclude with a discussion of the different ways that precision
      flashes could be parlayed during sleep to effect neuroadaptive changes in brain
      function. This article is a contribution to a special issue on Circadian Rhythms
      in Regulation of Brain Processes and Role in Psychiatric Disorders curated by
      editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos.

PMID- 29593786
TI  - Acoustic Trauma Changes the Parvalbumin-Positive Neurons in Rat Auditory Cortex.
AB  - Acoustic trauma is being reported to damage the auditory periphery and central
      system, and the compromised cortical inhibition is involved in auditory
      disorders, such as hyperacusis and tinnitus. Parvalbumin-containing neurons (PV
      neurons), a subset of GABAergic neurons, greatly shape and synchronize neural
      network activities. However, the change of PV neurons following acoustic trauma
      remains to be elucidated. The present study investigated how auditory cortical PV
      neurons change following unilateral 1 hour noise exposure (left ear, one octave
      band noise centered at 16 kHz, 116 dB SPL). Noise exposure elevated the auditory
      brainstem response threshold of the exposed ear when examined 7 days later. More
      detectable PV neurons were observed in both sides of the auditory cortex of noise
      exposed rats when compared to control. The detectable PV neurons of the left
      auditory cortex (ipsilateral to the exposed ear) to noise exposure outnumbered
      those of the right auditory cortex (contralateral to the exposed ear).
      Quantification of Western blotted bands revealed higher expression level of PV
      protein in the left cortex. These findings of more active PV neurons in noise
      exposed rats suggested that a compensatory mechanism might be initiated to
      maintain a stable state of the brain.

PMID- 29593787
TI  - Utilization of Smartphone Applications by Anesthesia Providers.
AB  - Health care-related apps provide valuable facts and have added a new dimension to
      knowledge sharing. The purpose of this study is to understand the pattern of
      utilization of mobile apps specifically created for anesthesia providers.
      Smartphone app stores were searched, and a survey was sent to 416 anesthesia
      providers at 136 anesthesiology residency programs querying specific facets of
      application use. Among respondents, 11.4% never used, 12.4% used less than once
      per month, 6.0% used once per month, 12.1% used 2-3 times per month, 13.6% used
      once per week, 21% used 2-3 times per week, and 23.5% used daily.
      Dosage/pharmaceutical apps were rated the highest as most useful. 24.6% of the
      participants would pay less than $2.00, 25.1% would pay $5.00, 30.3% would pay $5
      $10.00, 9.6% would pay $10-$25.00, 5.1% would pay $25-$50.00, and 5.1% would pay
      more than $50.00 if an app saves 5-10 minutes per day or 30 minutes/week. The use
      of mobile phone apps is not limited to reiterating information from textbooks but
      provides opportunities to further the ever-changing field of anesthesiology. Our
      survey illustrates the convenience of apps for health care professionals.
      Providers must exercise caution when selecting apps to ensure best evidence-based
      medicine.

PMID- 29593785
TI  - Circadian Regulation of Hippocampal-Dependent Memory: Circuits, Synapses, and
      Molecular Mechanisms.
AB  - Circadian modulation of learning and memory efficiency is an evolutionarily
      conserved phenomenon, occurring in organisms ranging from invertebrates to higher
      mammalian species, including humans. While the suprachiasmatic nucleus (SCN) of
      the hypothalamus functions as the master mammalian pacemaker, recent evidence
      suggests that forebrain regions, including the hippocampus, exhibit oscillatory
      capacity. This finding, as well as work on the cellular signaling events that
      underlie learning and memory, has opened promising new avenues of investigation
      into the precise cellular, molecular, and circuit-based mechanisms by which clock
      timing impacts plasticity and cognition. In this review, we examine the complex
      molecular relationship between clock timing and memory, with a focus on
      hippocampal-dependent tasks. We evaluate how the dysregulation of circadian
      timing, both at the level of the SCN and at the level of ancillary forebrain
      clocks, affects learning and memory. Further, we discuss experimentally validated
      intracellular signaling pathways (e.g., ERK/MAPK and GSK3beta) and potential
      cellular signaling mechanisms by which the clock affects learning and memory
      formation. Finally, we examine how long-term potentiation (LTP), a synaptic
      process critical to the establishment of several forms of memory, is regulated by
      clock-gated processes.

PMID- 29593788
TI  - In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe
      brasiliensis (Crassulaceae) Leaves.
AB  - The species Kalanchoe brasiliensis, known as "Saiao," has anti-inflammatory,
      antimicrobial, and antihistamine activities. It also has the quercetin and
      kaempferol flavonoids, which exert their therapeutic activities. With extensive
      popular use besides the defined therapeutical properties, the study of possible
      side effects is indispensable. The objective of this study is to evaluate the
      toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K.
      brasiliensis. The action of the extract (concentrations from 0.1 to 1000 uL/100
      uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity
      and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg
      orally, following recognized protocols. The in vitro results indicated cytotoxic
      activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the
      activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo,
      the extract showed no significant toxicity; only liver changes related to acute
      toxicity and some signs of liver damage, combining biochemical and histological
      data. In general, the extract showed low or no toxicity, introducing itself as
      safe for use with promising therapeutic potential.

PMID- 29593790
TI  - Association between Dietary Patterns and Precocious Puberty in Children: A
      Population-Based Study.
AB  - Objective: The aim of the present study was to investigate the association
      between dietary patterns and precocious puberty among Shanghai children. Methods:
      A cross-sectional study was conducted among Shanghai children by multistage
      stratified cluster random sampling in June 2014. Diet was assessed using a
      simplified food frequency questionnaire (FFQ). Height, weight, and Tanner stages
      of breast development, pubic hair growth, and testicular volume were carefully
      measured. Exploratory factor analysis was used to identify dietary patterns, and
      logistic regression analysis was used to assess the association between dietary
      patterns and precocious puberty. Results: Three distinct dietary patterns,
      "traditional diet," "unhealthy diet," and "protein diet," were established.
      Neither the "traditional diet" pattern nor the "protein diet" pattern showed any
      association with precocious puberty, taking gender, BMI, and adjustment factors
      into consideration. The "unhealthy diet" pattern was significantly positively
      associated with precocious puberty in both boys (OR = 1.24, 95% CI = 1.02-1.51)
      and girls (OR = 1.31, 95% CI = 1.10-1.56). The relationship remained positive
      only for girls (OR = 1.25, 95% CI = 1.04-1.49) after adjustment for age and BMI
      but statistically nonsignificant after further adjustment for socioeconomic
      factors in both boys and girls. Conclusions: Dietary patterns were found to be
      related to precocious puberty among Shanghai children.

PMID- 29593791
TI  - Histopathological Characterization and Whole Exome Sequencing of Ectopic Thyroid:
      Fetal Architecture in a Functional Ectopic Gland from Adult Patient.
AB  - Ectopic thyroid results from a migration defect of the developing gland during
      embryogenesis causing congenital hypothyroidism. But it has also been detected in
      asymptomatic individuals. This study aimed to investigate the histopathological,
      functional, and genetic features of human ectopic thyroids. Six samples were
      histologically examined, and the expression of the specific thyroid proteins was
      assessed by immunohistochemistry. Two samples were submitted to whole exome
      sequencing. An oropharynx sample showed immature fetal architecture tissue with
      clusters or cords of oval thyrocytes and small follicles; one sample exhibited a
      normal thyroid pattern while four showed colloid goiter. All ectopic thyroids
      expressed the specific thyroid genes and T4 at similar locations to those
      observed in normal thyroid. No somatic mutations associated with ectopic thyroid
      were found. This is the first immature thyroid fetal tissue observed in an
      ectopic thyroid due to the arrest of structural differentiation early in the
      colloid stage of development that proved able to synthesize thyroid hormone but
      not to respond to TSH. Despite the ability of all ectopic thyroids to synthetize
      specific thyroid proteins and T4, at some point in life, it may be insufficient
      to support body growth leading to hypothyroidism, as observed in some of the
      patients.

PMID- 29593792
TI  - GH, IGF-1, and Age Are Important Contributors to Thyroid Abnormalities in
      Patients with Acromegaly.
AB  - Purpose: To determine the prevalence, risk factors, and possible mechanisms of
      structural and endocrinological changes to the thyroid in acromegaly. Methods: We
      studied 93 acromegalic patients from PUMCH between January 2013 and December
      2013. The demographic and clinical information were recorded. Specimens of
      pituitary adenomas and thyroid cancer were collected for BRAF mutation
      assessments. Results: Thyroid morphological abnormalities were found in 72
      (77.4%) patients. Three (3.2%) were diagnosed with thyroid cancer. The thyroid
      gland volume was significantly increased in patients with higher random GH (p =
      0.01), higher nadir GH (p = 0.008), and higher IGF-1 level (p = 0.018). Age (p =
      0.002) was an independent risk factor for thyroid morphological abnormalities in
      acromegaly. The GH burden was significantly higher in patients with thyroid
      morphological abnormalities (p = 0.036). The BRAF V600E mutation was detected in
      the PTCs of the two patients with thyroid cancer. Conclusions: Both benign and
      malignant thyroid abnormalities are increased in the acromegalic population
      compared to those in the general population. Age at diagnosis is an independent
      risk factor for thyroid abnormalities, and GH burden may be a partial
      contributor. Early diagnosis, early treatment, and monitoring of postoperational
      endocrine levels are important for acromegalic patients.

PMID- 29593789
TI  - Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue.
AB  - Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis
      characterized by visceral obesity, atherogenic dyslipidemia, arterial
      hypertension, and insulin resistance. The growing prevalence of metabolic
      syndrome will certainly contribute to the burden of cardiovascular disease.
      Obesity and dyslipidemia are main features of metabolic syndrome, and both can
      present with adipose tissue dysfunction, involved in the pathogenic mechanisms
      underlying this syndrome. We revised the effects, and underlying mechanisms, of
      the current approved drugs for dyslipidemia and obesity (fibrates, statins,
      niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion,
      phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose
      tissue. Specifically, we explored how these drugs can modulate the complex
      pathways involved in metabolism, inflammation, atherogenesis, insulin
      sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation
      by these drugs, as well as differences of major importance for clinical practice
      between drugs of the same class, were identified. Whether solutions to these
      issues will be found in further adjustments and combinations between drugs
      already in use or necessarily in new advances in pharmacology is not known. To
      better understand the effect of drugs used in dyslipidemia and obesity on adipose
      tissue not only is challenging for physicians but could also be the next step to
      tackle cardiovascular disease.

PMID- 29593793
TI  - Soft Lithography and Minimally Human Invasive Technique for Rapid Screening of
      Oral Biofilm Formation on New Microfabricated Dental Material Surfaces.
AB  - Introduction: Microfabrication offers opportunities to study surface concepts
      focused to reduce bacterial adhesion on implants using human minimally invasive
      rapid screening (hMIRS). Wide information is available about cell/biomaterial
      interactions using eukaryotic and prokaryotic cells on surfaces of dental
      materials with different topographies, but studies using human being are still
      limited. Objective: To evaluate a synergy of microfabrication and hMIRS to study
      the bacterial adhesion on micropatterned surfaces for dental materials. Materials
      and Methods: Micropatterned and flat surfaces on biomedical PDMS disks were
      produced by soft lithography. The hMIRS approach was used to evaluate the total
      oral bacterial adhesion on PDMS surfaces placed in the oral cavity of five
      volunteers (the study was approved by the University Ethical Committee). After 24
      h, the disks were analyzed using MTT assay and light microscopy. Results: In the
      present pilot study, microwell structures were microfabricated on the PDMS
      surface via soft lithography with a spacing of 5 um. Overall, bacterial adhesion
      did not significantly differ between the flat and micropatterned surfaces.
      However, individual analysis of two subjects showed greater bacterial adhesion on
      the micropatterned surfaces than on the flat surfaces. Significance:
      Microfabrication and hMIRS might be implemented to study the cell/biomaterial
      interactions for dental materials.

PMID- 29593794
TI  - Comparative Analysis of the Effectiveness of the Topical Administration of
      Benzocaine and EMLA(r) on Oral Pain and Tactile Sensitivity.
AB  - Objectives: To compare the effectiveness of the topical administration of
      benzocaine and EMLA on oral pain and tactile sensitivity. Materials and Methods:
      A randomized, double-blind, split-mouth clinical trial was carried out with 20
      volunteers. The sensorial and quantitative tests were applied before the contact
      with topical anesthetic and after the application. Results: In the superficial
      tactile perception test, when we compared each group singly, there were
      statistically significant values in the decrease of superficial tactile
      perception when compared to the moment prior to the application of anesthetic
      agents. For the sensitivity to mechanical pain, no statistical significant
      difference was observed at evaluated times. In the needle penetration test, in an
      intergroup analysis, we found a decrease in the pain sensitivity to needle
      penetration at 5 min (p=0.053) and at 10 min (p=0.019) after the contact of the
      anesthetic drug with the oral mucosa. Conclusion: The application of topical
      anesthetic drugs reduces the discomfort associated with this procedure, mainly
      until the first 10 minutes. Only the needle penetration sensitivity test showed
      sufficient sensitivity to reveal a difference in the anesthetic effect between
      EMLA and benzocaine. This trial is registered with RBR-2N2GSW.

PMID- 29593795
TI  - The Role and Impact of Salivary Zn Levels on Dental Caries.
AB  - Introduction: Minimal attention has been given to the role of salivary
      microelements, the importance they have in reducing the intensity of caries, and
      the effect of caries prophylaxes. Aim: This research aimed to determine the
      concentration and quantity of Zn and its impact on the prevention and the
      reduction of the intensity of caries in schoolchildren aged 12-13 years with
      permanent dentition. Methods: For this research, we analyzed the stimulated and
      nonstimulated full saliva of 106 schoolchildren divided into three groups by mean
      decayed, missing, and filled teeth (DMFT) index. The control group consisted of
      25 caries-free children, the second group had 47 children with mean DMFT index of
      1 to 6, and the third group had 34 children with DMFT index of >= 6. Complete
      saliva was collected from all children in a sterile test tube. Results: The
      concentration of Zn in saliva before stimulation in caries-free children has
      variations of the order of 0.001+ to 0.01 mmol/l. The maximum concentration after
      stimulation is 6.72 mmol/l, while the maximum value is 64.38 mmol/l. Conclusion:
      The Zn concentration in the stimulated saliva showed a significant increase in
      the group of caries-free children and could be described as a positive value for
      the reduction of caries.

PMID- 29593796
TI  - Application of D-Amino Acids as Biofilm Dispersing Agent in Dental Unit
      Waterlines.
AB  - Aim and Purpose: Biofilms in dental unit waterlines (DUWLs) are extremely
      difficult to eliminate. Aim of this study is to evaluate the efficacy of a
      mixture of four D-amino acids on biofilm dispersion in DUWLs. Materials and
      Methods: A mixture of four D-amino acids (D-methionine, D-tryptophan, D-leucine,
      and D-tyrosine, 10 mM each), distilled water (control), and 0.1 M hydrochloric
      acid (HCl) was used in the experiment. In laboratory, pieces of DUWLs covered
      with biofilms were submerged in different solutions for 5 days, flushed, and
      measured OD600 of the dispersed biofilms. Remnants of biofilms on the DUWLs were
      evaluated by SEM. In clinic, fifteen DCUs were incubated with test and control
      solutions, flushed, and measured OD600 of the dispersed biofilms. Microbial count
      of DUWL output water was enumerated twice a week for four weeks. Results: There
      was a slight, but not significant, increase in OD600 of flushing water in D-amino
      acids group. D-amino acids effectively reduced bacterial plaque as demonstrated
      by SEM. Incubation with D-amino acids significantly reduced biofilms especially
      after the first day of flushing. Bacterial count in DUWL output water was
      significantly reduced after treatment with D-amino acids. Conclusion: D-amino
      acids are applicable as biofilm dispersing agents in DUWLs.

PMID- 29593797
TI  - Factors influencing P terminal force in lead V1 of the ECG in hemodialysis
      patients.
AB  - Introduction: Atrial fibrillation (AF) is a highly prevalent arrhythmia in
      hemodialysis (HD) patients, and an HD session may be a trigger for AF episodes.
      An abnormal P-terminal force in lead V1 (PTFV1) may predict new-onset AF in HD
      patients. The aim of the study was to assess the influence of the HD process on
      PTFV1 and to evaluate possible factors influencing PTFV1 in a group of selected
      HD patients. Material and methods: One hundred and fifty-three selected HD
      patients entered the study. Blood chemistry, electrocardiography, and impedance
      cardiography were evaluated before and after HD. Echocardiography was performed
      on the morning after dialysis. Abnormal PTFV1 was defined as PTFV1 > 40 mm * ms.
      Results: Abnormal PTFV1 was found in 35.3% of patients before dialysis and in
      48.4% of patients after dialysis. The results of multiple regression analysis
      revealed that the independent predictors of pre-dialysis abnormal PTFV1 were:
      left atrial volume index (p = 0.002), left ventricular mass index (p = 0.014),
      and pre-dialysis thoracic fluid content (p = 0.021) values. The independent
      predictors of HD-induced abnormal PTFV1 values were larger differences between
      pre-dialysis and post-dialysis values of serum potassium (p < 0.001) and mean
      arterial pressure (p = 0.008). Conclusions: Abnormal PTFV1 is prevalent in HD
      patients. The HD process adversely affects PTFV1 values. Pre-dialysis abnormal
      PTFV1 is mainly associated with structural heart abnormalities and hydration
      status. HD-induced abnormal PTFV1 is associated predominantly with serum
      potassium changes as well as HD-induced hypotension. Our results suggest possible
      risk factors for AF; however, their clinical significance needs to be confirmed
      in follow-up studies.

PMID- 29593798
TI  - Depressive symptoms but not chronic pain have an impact on the survival of
      patients undergoing maintenance hemodialysis.
AB  - Introduction: More than 1/3 of patients with end-stage renal disease who are in a
      chronic dialysis program suffer from chronic pain and depression/anxiety. The aim
      of the study was to determine the impacts of symptoms of depression/anxiety,
      chronic pain and quality of life (QoL) on 6-year patient survival. Material and
      methods: Observational study of end-stage renal disease patients on maintenance
      hemodialysis (n = 205) who met the inclusion criteria. Patients from three
      dialysis centers in Lower Silesia were asked to complete a battery of validated
      questionnaires: the Hospital Anxiety and Depression Scale (HADS), the 36-item
      Short Form Health Survey Questionnaire, the Verbal Rating Scale (VRS) and the
      Visual Analog Scale (VAS). Clinical and biochemical data (dialysis adequacy) were
      recorded. Results: One hundred thirty from 205 enrolled hemodialysis patients
      (63.4%) suffered from chronic pain. Patients with pain were on maintenance
      dialysis for longer times and had higher levels of parathyroid hormone, more
      depressive symptoms and a lower QoL than those without pain. In the 6-year
      period, 96 (46.8%) patients died. The most common cause of death was
      cardiovascular disease in 44 (45.8%) patients. Highly depressed patients (HADS
      depression score > 8) exhibited higher mortality (< 8 vs. > 8 points; p = 0.016)
      independent of age, diabetes, cardiovascular disease, C-reactive protein or
      albumin level. Conclusions: Chronic pain, although common among hemodialysis
      patients, did not lower survival. Depressive symptoms are an important predictor
      for all-cause mortality in hemodialysis patients, with the relationship
      independent of nutritional or inflammatory status.

PMID- 29593799
TI  - Comparison of the efficacy and safety of hybrid and sequential therapies as a
      first-line regimen for Helicobacter pylori infection in Turkey.
AB  - Introduction: Helicobacter pylori infection is a common infection worldwide. The
      most frequently recommended treatment for eradication of H. pylori remains triple
      therapy. In this study, we compared sequential and hybrid regimens for H. pylori
      eradication in a region of Turkey with high resistance to clarithromycin.
      Material and methods: Three hundred and forty H. pylori-positive patients were
      enrolled in the study. The subjects were randomly divided into two groups. The
      first group (170 patients) received rabeprazole (40 mg/b.i.d.) and amoxicillin
      (1000 mg/b.i.d.) for 2 weeks and metronidazole and clarithromycin (500 mg/b.i.d.)
      during the second week in the hybrid therapy group. The second group (170
      patients) received rabeprazole (40 mg/b.i.d.) for 14 days, amoxicillin (1000
      mg/b.i.d.) for the first 7 days, and metronidazole plus clarithromycin (each 500
      mg/b.i.d.) during the next 7 days in the sequential therapy group. Results: In
      the per-protocol analysis, the eradication rate in the hybrid therapy group was
      96.1% (147/153), and in the sequential therapy group it was 90.9% (140/154).
      There was no significant difference between the two groups (p = 0.06). Ninety
      seven of those 340 patients reported minor adverse drug reactions. The
      percentages of patients with adverse reactions were 30.6% in the hybrid therapy
      group and 26.5% in the sequential therapy group (p = 0.74). Conclusions: Both
      therapies are highly effective for eradication of H. pylori, and could be
      recommended as a first-line therapy in regions with high antibiotic resistance.

PMID- 29593800
TI  - Activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in sera
      of patients with hepatitis C.
AB  - Introduction: The changes of enzyme activity in the hepatocytes in the course of
      different liver diseases are reflected by increase of the corresponding enzyme
      activity in the plasma. For example, the activities of alcohol dehydrogenase
      (ADH) and aldehyde dehydrogenase (ALDH) correlate with the severity of the
      condition during cirrhosis. In this study we measured the activity of ADH
      isoenzymes and ALDH in the sera of patients with hepatitis C. Material and
      methods: Serum samples were taken from 60 patients suffering from viral hepatitis
      C and from 66 control subjects. Total ADH activity and class III and IV
      isoenzymes were measured by the photometric method and ALDH activity, ADH I and
      II by the fluorometric method. Results: The ADH activity was significantly higher
      in patients with hepatitis C than in healthy (p < 0.001). The total activity of
      ADH was 1284 mU/l in patients, and 745 mU/l (controls). The activity of
      isoenzymes classes ADH I and ADH II in the hepatitis C group increased
      respectively 55% (4.24 vs. 1.88 mU/l; p < 0.001) and 47% (26.63 vs. 14.11 mU/l; p
      < 0.001) in the comparison to the control. There was significant increase in the
      activity of ADH I isoenzyme (4.96 vs. 3.81 mU/l; p < 0.001) and ADH total (1833
      vs. 1105 mU/l; p < 0.001) in patients with high viral load in comparison to
      patients with low viral load. Conclusions: The activity of class I and II ADH
      isoenzymes in the sera of patients with hepatitis C is increased, and it seems to
      be caused by the release of these isoenzymes from damaged liver cells.

PMID- 29593801
TI  - Inflammatory mediators in the diagnosis and treatment of acute pancreatitis:
      pentraxin-3, procalcitonin and myeloperoxidase.
AB  - Introduction: Acute pancreatitis (AP) is the third most common gastrointestinal
      disease at hospital admission. The etiology and pathogenesis of this disease are
      not completely clear. Our study was intended to determine the systemic levels of
      pentraxin-3 (PTX-3), myeloperoxidase (MPO), procalcitonin (PCT), and C-reactive
      protein (CRP) as prognostic parameters in early stages of AP. We also determined
      the effects of treatment on PTX-3, MPO, PCT and CRP levels in AP. Material and
      methods: The study group comprised 44 AP patients (22 male, 22 female; age: 49.3
      +/-16.9 years) referred to our outpatient clinic. Additionally, our investigation
      included a control group of 30 healthy volunteers (18 male, 12 female; age: 50.8
      +/-12.6 years). Results: Leukocytes, glucose, aspartate aminotransferase (AST
      (SGOT)), alanine aminotransferase (ALT (SGPT)), alkaline phosphatase (ALP), total
      and direct bilirubin levels were significantly higher in the AP group (p < 0.05,
      all). CRP, PTX-3, MPO and PCT were considerably higher in the AP group (p <
      0.001, all), and after treatment, CRP, PTX-3, MPO and PCT levels were
      significantly lower (p < 0.001, all). Conclusions: Our findings indicated that
      the CRP, PTX-3, MPO and PCT levels increase in patients with AP and hence these
      indicators can be used as diagnostic factors to predict inflammation severity in
      AP. It was revealed that after treatment, there were significant reductions in
      biomarker levels. However, further research is needed in order to understand how
      these biomarkers can help to monitor inflammatory responses in AP.

PMID- 29593802
TI  - Oxygen dependence of endothelium-dependent vasodilation: importance in chronic
      obstructive pulmonary disease.
AB  - Introduction: Epidemiological studies have shown increased morbidity and
      mortality in patients with coronary artery disease (CAD) and chronic obstructive
      pulmonary disease (COPD). We aimed to characterize the oxygen dependence of
      endothelial function in patients with CAD and coexisting COPD. Material and
      methods: In CAD patients with and without COPD (n = 33), we non-invasively
      measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the
      brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous
      microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental
      setup, vascular function was assessed in healthy volunteers (n = 5) breathing 12%
      oxygen or 100% oxygen in comparison to room air. Results: COPD was associated
      with impaired FMD (3.4 +/-0.5 vs. 4.2 +/-0.6%; p < 0.001) and increased IMT (0.49
      +/-0.04 vs. 0.44 +/-0.04 mm; p <0.01), indicating functional and structural
      alterations of the BA in COPD. Forearm blood flow and LDPI were comparable
      between the groups. Flow-mediated dilation correlated with capillary oxygen
      pressure (pO2, r = 0.608). Subgroup analysis in COPD patients with pO2 > 65 mm Hg
      and pO2 <= 65 mm Hg revealed even lower FMD in patients with lower pO2 (3.0 +/
      0.5 vs. 3.7 +/-0.4%; p < 0.01). Multivariate analysis showed that pO2 was a
      predictor of FMD independent of the forced expiratory volume and pack years.
      Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100%
      oxygen did not change vascular function. Conclusions: Our data suggest that in
      CAD patients with COPD, decreased systemic oxygen levels lead to endothelial
      dysfunction, underlining the relevance of cardiopulmonary interaction and the
      potential importance of pulmonary treatment in secondary prevention of vascular
      disease.

PMID- 29593803
TI  - Can we define migraine patients with blood high-sensitivity C-reactive protein
      and galectin-3 levels in the emergency department?
AB  - Introduction: Migraine, the most widespread cause of headache in young adults, is
      a frequent reason for presentation to emergency departments. The aim of this
      study was to determine the diagnostic value of serum galectin-3 and high
      sensitivity C-reactive protein (hsCRP) levels in migraine patients. Material and
      methods: Serum galectin-3 and hsCRP levels were measured using enzyme-linked
      immunosorbent assay in 70 migraine patients and 70 healthy control subjects.
      Results: The mean values of hsCRP and galectin-3 levels were significantly higher
      in the migraine group than those in the control group (1.67 +/-0.49, 1.12 +/-0.38
      mg/l, p < 0.001; and 3.76 +/-1.45, 2.05 +/-0.29 ng/ml, p < 0.001, respectively).
      When the diagnostic values of the biomarkers were assessed in the migraine attack
      and control groups, the sensitivity and specificity of the test for hsCRP at the
      cut-off point of 1.32 mg/l were 70% and 73% (AUC = 0.805, 95% CI: 0.74-0.88, p <
      0.001), and for galectin-3 at the cut-off point of 2.4 ng/ml, 89% and 90% (AUC =
      0.97, 95% CI: 0.95-0.99, p < 0.001), respectively. Conclusions: This study showed
      the presence of a relation between high serum levels of hsCRP and galectin-3 in
      migraine patients. However, well-controlled, carefully executed longitudinal
      studies are required to confirm these findings.

PMID- 29593804
TI  - CXCL9 concentrations in cerebrospinal fluid and serum of patients with tick-borne
      encephalitis.
AB  - Introduction: The aim of our current study was to evaluate cerebrospinal fluid
      (CSF) and serum CXCL9 concentrations and diagnostic usefulness of this molecule
      in tick-borne encephalitis (TBE). The study included TBE patients in the acute
      phase (TBE I) and after 2 weeks of follow-up (TBE II). The control group
      consisted of patients investigated for suspected central nervous system (CNS)
      infection, but with normal CSF findings. Material and methods: Concentrations of
      CXCL9 were measured using enzyme-linked immunosorbent assay (ELISA). Results:
      Cerebrospinal fluid and serum concentrations of CXCL9 in patients with TBE were
      significantly higher than in controls (p < 0.001). This alteration was also
      observed in the case of the CXCL9 index (ICXCL9; CSF CXCL9 concentration divided
      by serum CXCL9 concentration) (p < 0.001); moreover, ICXCL9 significantly
      decreased after 2 weeks (p < 0.001). This is the first study to evaluate the CSF
      and serum levels of CXCL9 in subjects with TBE. Conclusions: CXCL9 is a ligand
      for CXCR3, which was found on all Th1 memory lymphocytes present in the
      peripheral blood; therefore the elevated concentrations of CXCL9 in TBE patients
      as compared to the controls might indicate that this chemokine perhaps takes part
      in the trafficking of Th1 cells into the CNS. The results presented here support
      the hypothesis that CXCL9 may play a role in TBE. However, further studies are
      required to determine whether this protein might be used as a potential tool for
      the diagnosis and monitoring of inflammation in TBE.

PMID- 29593805
TI  - Evaluating the introduction of intraoperative neuromonitoring of the recurrent
      laryngeal nerve in thyroid and parathyroid surgery.
AB  - Introduction: Paresis of the recurrent laryngeal nerve (RLN) is a complication of
      thyroid surgery. Neuromonitoring as is gaining acceptance among surgeons. The aim
      of the study was to assess the number of technical problems in the initial phase
      of intraoperative neuromonitoring (IONM) use and the specificity, sensitivity,
      positive predictive value and negative predictive value of neuromonitoring. The
      number of cases of postoperative paresis (transient and permanent) was assessed.
      Material and methods: The prospective analysis included 101 thyroid operations
      with IONM (190 RLNs at risk of injury) in the period from January to April, 2012.
      Demographic data, rate of RLN identification, sensitivity, specificity and
      predictive value of the method, the duration of the procedure and the percentage
      of RLN paresis were considered. Results: The RLN was identified in 92% of the
      cases. Technical problems were observed in 12.98%, of which 61% were due to
      incorrect positioning of the endotracheal tube electrodes in relation to the
      vocal cords. The sensitivity, specificity, negative and positive predictive value
      and the accuracy of the method were respectively 71%, 98%, 62.5%, 98.9% and 97%.
      Early nerve injury occurred in 3.7% of the cases; 2.6% were temporary paresis and
      1.1% permanent. Conclusions: During the initial stages of implementing IONM we
      experienced technical problems that required correction in every tenth patient.
      The positive predictive value was relatively low; nevertheless, good results in
      terms of the rate of accurate identification of the RLN as well as the low rate
      of RLN paresis support the use of this method.

PMID- 29593806
TI  - Consequences of bleeding after thyroid surgery - analysis of 7805 operations
      performed in a single center.
AB  - Introduction: Surgical treatment of thyroid gland diseases is associated with the
      possibility of severe complications. The most dangerous of them is bleeding.
      Current studies focus on its risk factors, rather than reoperation-related
      consequences. Material and methods: We analyzed 7805 thyroid operations performed
      from 1996 to 2014 in the Clinic of General, Gastroenterological and Endocrine
      Surgery of Wroclaw Medical University. Typical risk factors, symptoms and
      consequences of bleeding were analyzed. Results: Among operated patients 88.2%
      were female and 11.8% male. Bleeding occurred in 84 (1.08%) patients. Sex (p =
      0.006), preoperative thyroid pathology (p = 0.03), and type of operation (p <
      0.001) are significant risk factors for bleeding, while retrosternal goiter and
      surgeon's experience are not. Risk of bleeding is highest in the case of male
      sex, toxic goiter and total resection of the thyroid gland. Most reoperations
      took place within 6 h. In 88.8% of cases of this kind of complication the surgeon
      indicated the exact source of bleeding; most commonly it was the neck muscles,
      skin and subcutaneous tissue, or the thyroid stump. Three patients required a
      second reoperation, 24 suffered further complications, and 8 required transfer to
      the Intensive Care Unit (ICU). Cardiac arrest occurred in 3 patients and 2
      suffered bilateral vocal cord palsy. Conclusions: Bleeding after thyroid
      operations is a direct life threat that requires immediate intervention. As a
      result death may occur, half of patients suffer other complications and some
      require intensive care. The risk is highest in the case of male sex, toxic goiter
      and total resection of the thyroid gland. Each patient after thyroid surgery
      needs to be closely observed. An operating theatre and ICU should be available at
      all times.

PMID- 29593807
TI  - Enhanced healing and anti-inflammatory effects of a carbohydrate polymer with
      zinc oxide in patients with chronic venous leg ulcers: preliminary results.
AB  - Introduction: Insufficient wound healing related to chronic inflammation of
      chronic venous leg ulcers (CVUs) represents an important public health problem.
      The aim of this study was to evaluate the effects of a carbohydrate polymer with
      zinc oxide therapy on CVUs. Material and methods: Forty patients with CVUs were
      recruited for this study and were divided into a study group and control group.
      Patients In the study group were instructed to use venous compression treatment
      andtopical carbohydrate polymer with zinc oxide twice daily, while patients In
      the control group were treated with only venous compression treatment. All
      patients were followed up for 8 weeks. Peripheral blood samples and biosy tissue
      specimens were obtained at the initiation of treatment and after 8 weeks to
      assess serum levels of inflammatory cytokines as well as the percentage of
      leukocytes, T-helper cells, cytotoxic-T cells, macrophages and endothelial cells
      in the biopsy tissue using flow cytometry. Results: A significantly greater
      reduction in the mean percentage ulcer area from baseline to eight weeks was
      observed in the study group (up to 40% for large ulcers). Furthermore, the
      patients in the study group had reduced systemic levels of the pro-inflammatory
      cytokines IL-8 (p = 0.0028) and IL-6 (p = 0.0302), fewer total CD45+ cells (p =
      0.0038) and more CD31+ cells (p = 0.045) present in ulcer biopsies compared to
      the control group. Conclusions: The carbohydrate polymer with zinc oxide
      treatment with venous compression enhances healing of CVUs and improves quality
      of life due, in part, to its anti-inflammatory properties.

PMID- 29593808
TI  - Evaluation of the validity of treatment decisions based on surrogate country
      models before introduction of the Polish FRAX and recommendations in comparison
      to current practice.
AB  - Introduction: Patients diagnosed before the Polish FRAX was introduced may
      require re-evaluation and treatment changes if the diagnosis was established
      according to a surrogate country FRAX score. The aim of the study was to evaluate
      the validity of treatment decisions based on the surrogate country model before
      introduction of the Polish FRAX and to provide recommendations based on the
      current practice. Material and methods: We evaluated a group of 142
      postmenopausal women (70.7 +/-8.9 years) who underwent bone mineral density
      measurements. We used 22 country-specific FRAX models and compared these to the
      Polish model. Results: The mean risk values for hip and major osteoporotic
      fractures within 10 years were 4.575 (from 0.82 to 8.46) and 12.47% (from 2.18 to
      21.65), respectively. In the case of a major fracture, 94.4% of women would
      receive lifestyle advice, and 5.6% would receive treatment according to the
      Polish FRAX using the guidelines of the National Osteoporosis Foundation (NOF).
      Polish treatment thresholds would implement pharmacotherapy in 32.4% of the study
      group. In the case of hip fractures, 45% of women according to the NOF would
      require pharmacotherapy but only 9.8% of women would qualify according to Polish
      guidelines. Nearly all surrogate FRAX calculator scores proved significantly
      different form Polish (p > 0.05). Conclusions: More patients might have received
      antiresorptive medication before the Polish FRAX. This study recommends re
      evaluation of patients who received medical therapy before the Polish FRAX was
      introduced and a review of the recommendations, considering the side effects of
      antiresorptive medication.

PMID- 29593809
TI  - The impact of age, sex, blepharitis, rosacea and rheumatoid arthritis on Demodex
      mite infection.
AB  - Introduction: Two human-specific Demodex species have been described: Demodex
      folliculorum and Demodex brevis. A medical condition caused by the presence of
      Demodex is called demodicosis. Material and methods: The study material comprised
      eyelashes collected from 1499 patients. Results: Demodex sp. infection was
      revealed in 47% of patients (487 women and 216 men). We determined the following
      rates of infection by age groups: 1-25 (8% of infected subjects), 26-40 (36%), 41
      55 (50%), 56-70 (67%), over 70 (77%). The sex of the subjects was not identified
      as a factor conducive to infection (p = 0.108), while their age was positively
      correlated with the risk of infection (p < 0.005). The 1499 study subjects
      included patients with blepharitis, rosacea, and rheumatoid arthritis. The study
      investigated the extent to which the above-mentioned conditions affect the risk
      of Demodex infection. Applying the method of logistic regression, the infection
      probability was estimated, depending on the age, sex, and comorbidities such as
      blepharitis, rosacea, and rheumatoid arthritis. Patients suffering from
      blepharitis were found to have a nearly 2.5-fold higher risk of Demodex infection
      than those without blepharitis, and the risk for rosacea patients was determined
      as three-fold higher than that of the general population. Conclusions:
      Blepharitis and rosacea are risk factors for Demodex infection.

PMID- 29593810
TI  - Francisella tularensis/Rickettsia spp. co-infections in patients with skin
      changes and lymphadenopathy.
AB  - Introduction: Tularemia and spotted fever group rickettsioses (SFG) can be
      transmitted by ticks and have a number of common clinical symptoms. Most
      characteristic are a maculopapular or vesicular rash or an eschar at the site of
      the tick or insect bite accompanied by painful lymph nodes. The aim of this study
      was to determine whether Rickettsia spp./Francisella tularensis mixed infections
      occurred in patients with similar symptoms who were diagnosed with either
      Rickettsia spp. or F. tularensis infection. Material and methods: Thirty-six
      cases from 2011-2014, including 15 individuals with clinically and serologically
      recognized SFG and 21 with tularemia, were analyzed retrospectively using
      immunofluorescence for detection of Rickettsia spp. or ELISA for detection of F.
      tularensis. Results: Of the 36 cases examined, specific high titers of antibodies
      to Rickettsia spp. were found in 1 (4.4%) patient with tularemia and specific
      high titers of antibodies to F. tularensis were detected in 1 (6.7%) patient with
      SFG. Conclusions: The results of our study show that in infections with fever,
      enlarged lymph nodes and skin lesions after tick and insect bites, laboratory
      testing of both diseases - SFG rickettsiosis and tularemia - should be
      implemented. Identification of F. tularensis and Rickettsia spp. mixed infections
      is crucial in order to administer appropriate antibiotics and to avoid treatment
      failure and relapse.

PMID- 29593811
TI  - Expression of selected genes of dendritic and Treg cells in blood and skin of
      morphea patients treated with UVA1 phototherapy.
AB  - Introduction: Morphea is a chronic autoimmune disease characterized by fibrosis
      of the skin. Dendritic cells (DC) and regulatory T cells (Tregs) play a
      significant role in development of autoimmune and tolerance mechanisms. The aim
      of the study was to establish the expression of selected genes of plasmacytoid
      and myeloid DC, Treg cells, and the microenvironment of cytokines (interleukin
      17A (IL-17A), transforming growth factor beta (TGF-beta)) in blood and skin of
      morphea patients. In addition, the effect of UVA1 phototherapy on expression of
      the aforementioned genes was evaluated. Material and methods: The study was
      performed on 15 blood and 10 skin samples from patients with morphea. The
      evaluation included expression of CLEC4C (C-type lectin domain family 4, member C
      receptor), Lymphocyte antigen 75 (LY75), Forkhead box p3 (foxp3) transcription
      factor, IL-17A and TGF-beta genes in peripheral blood mononuclear cells (PBMC)
      and in skin samples both before and after UVA1 phototherapy using real-time
      polymerase chain reaction. Results: The study revealed lower expression of CLEC4C
      before (p = 0.010) and after (p = 0.009) phototherapy and lower expression of IL
      17A before (p = 0.038) phototherapy in PBMC of patients with morphea vs. the
      control group. Expression of CLEC4C in PBMC correlated negatively (rho = -0.90; p
      = 0.001) with activity of disease after phototherapy. No significant differences
      were found between expression of analysed genes before and after UVA1 therapy in
      PBMC and skin of morphea patients. Conclusions: The results do not confirm the
      involvement of analysed subsets of DC and Tregs in UVA1 phototherapy in morphea,
      but point to CLEC4C as a possible biomarker associated with the disease activity.

PMID- 29593812
TI  - The effect of celastrol on learning and memory in diabetic rats after sevoflurane
      inhalation.
AB  - Introduction: The aim was to devise an animal model showing some of the
      neuropathological changes seen in senile dementia, and to investigate the effect
      of celastrol on cognition neuropathology in this model. Material and methods:
      Forty male Sprague Dawley rats weighing 300-350 g were randomly divided into 5
      groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus
      (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled
      sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal
      injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group
      rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air.
      Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg)
      daily for 4 days, while the control group received intraperitoneal injections of
      an equal volume of dimethylsulfoxide. The Morris water maze test was performed to
      test cognition. Animals were killed after the last water maze test and Congo red
      staining was used to observe deposition of amyloid substance in the hippocampus.
      The expression of GFAP and IGF-1 in the hippocampus was observed by
      immunohistochemistry. Results: Diabetes decreased cognition, increased amyloid
      substance and GFAP expression, and decreased IGF-1 expression in the hippocampus
      (all p-values < 0.05). Sevoflurane administration intensified and celastrol
      decreased these changes (all p-values < 0.05). Conclusions: Sev/DM rats showed
      cognitive and neurochemical changes similar to those seen in senile dementia.
      Celastrol decreased these changes and should be evaluated further as a possible
      clinical agent in dementia.

PMID- 29593813
TI  - The role of vitamin E in the prevention of zoledronic acid-induced nephrotoxicity
      in rats: a light and electron microscopy study.
AB  - Introduction: Bisphosphonates are widely used in metastatic cancer such as
      prostate and breast cancer, and their nephrotoxic effects have been established
      previously. In this study we aimed to evaluate both the nephrotoxic effects of
      zoledronic acid (ZA) and the protective effects of vitamin E (Vit-E) on this
      process under light and electron microscopy. Material and methods: A total of 30
      male Sprague-Dawley rats were divided into 3 groups. The first group constituted
      the control group. The second group was given i.v. ZA of 3 mg/kg once every 3
      weeks for 12 weeks from the tail vein. The third group received the same dosage
      of ZA with an additional i.m. injection of 15 mg Vit-E every week for 12 weeks.
      Tissues were taken 4 days after the last dose of ZA for histopathological and
      ultrastructural evaluation. Paller score, tubular epithelial thickness and basal
      membrane thickness were calculated for each group. Results: For group 2, the p
      values are all < 0.001 for Paller score, epitelial thickness, and basal membrane
      thickness. For group 3 (ZA + Vit. E), the p-values are < 0.001 for Paller score,
      0.996 for epitelial thickness, and < 0.001 basal membrane thickness. Significant
      differences were also observed in ultrastructural changes for group 2. However,
      adding Vit-E to ZA administration reversed all the histopathological changes to
      some degree, with statistical significance. Conclusions: Administration of ZA had
      nephrotoxic effects on rat kidney observed under both light and electron
      microscopy. Concomitant administration of Vit-E significantly reduces toxic
      histopathological effects of ZA.

PMID- 29593814
TI  - Age-related differences in function and structure of rat livers subjected to
      ischemia/reperfusion.
AB  - Introduction: Liver function is affected during ischemia/reperfusion (IR). The
      current state of knowledge about liver aging processes during IR is incomplete.
      We evaluated the effects of aging on liver structure and function under IR
      conditions. Material and methods: Animals were divided into control (C-2) and
      ischemia/reperfusion (IR-2) groups of young rats (2-4 months old) and C-12 and IR
      12 groups of old rats (12-14 months old). The livers from IR-2 and IR-12 groups
      were subjected to partial ischemia (60 min), followed by global reperfusion (4
      h). Blood samples were obtained during reperfusion (0, 30 and 240 min) to
      estimate the activity of aminotransferases (ALT, AST). After IR, tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1b (IL-1b), malondialdehyde (MDA), and
      superoxide dismutase (SOD) were determined in liver homogenates. Results: At all
      points of reperfusion, an increase in aminotransferase activity levels in the
      ischemic groups was observed; mainly between IR-12 and C-12 rats. The
      concentration of TNF-alpha was significantly higher in young animals (in non
      ischemic groups: p = 0.09, in ischemic groups: p = 0.05). Under IR conditions,
      the concentration of IL-1b dropped (p = 0.05). The concentration of MDA was
      significantly higher in mature animals (in non-ischemic groups: p = 0.09, in
      ischemic groups: p = 0.05). In ischemic groups an increase in necrosis rate was
      observed regardless of age. Rats in the IR-12 group showed the most pronounced
      changes in hepatic architecture, including increased micro- and macrosteatosis
      and parenchymal cell destruction. Conclusions: The function and structure of
      mature livers slightly deteriorate with age and these differences are more
      noticeable under IR conditions.

PMID- 29593815
TI  - Preventive effects of total saponins of Panax japonicus on fatty liver fibrosis
      in mice.
AB  - Introduction: Nonalcoholic fatty liver disease (NAFLD) is a condition in which
      excess fat accumulates in the liver of a patient without a history of alcohol
      abuse. Fatty liver fibrosis, a severe form of NAFLD, is a key step which can be
      reversed by effective medical intervention. This paper aims to describe the
      protective role and mechanisms of action of total saponins of Panax japonicus
      (SPJ) against fatty liver fibrosis in mice. In this study, fatty liver fibrosis
      was induced by a high-fat (HF) diet combined with intraperitoneal injection of
      porcine serum. Material and methods: The fatty liver fibrosis model was induced
      by HF diet combined with intraperitoneal injection of porcine serum. The
      endoplasmic reticulum stress (ERS) response and C/EBP homologous protein (CHOP)
      and p-Jun N-terminal kinase (JNK)-mediated apoptosis and inflammation were
      assessed by serum biochemistry, hematoxylin-eosin (H + E), Masson and electronic
      microscopy staining, Hyp content detection, Western blotting and real time
      polymerase chain reaction (RT-PCR). Results: Saponins of Panax japonicus could
      significantly improve liver function and decrease the lipid level in the serum.
      The liver steatosis, collagen fibers and inflammatory cell infiltration were
      significantly improved in the SPJ group according to microscope observation. The
      RT-PCR analysis revealed that the collagen I (Coll), alpha smooth muscle actin
      (alpha-SMA), tissue inhibitors of MMPs (TIMP), CHOP and GRP78 mRNA expression
      levels were distinctly weakened by SPJ treatment; and western blotting analysis
      indicated that the phosphorylated JNK (p-JNK), Coll and 78 kD glucose-regulated
      protein (GRP78) protein expression levels were significantly alleviated, which
      might be associated with the inhibition of the ERS response and the CHOP and JNK
      mediated apoptosis and inflammation pathway. Conclusions: Based on this research,
      SPJ as a preventive medicine has great potential in prevention of liver fibrosis.

PMID- 29593816
TI  - Pancreatic-like enzymes of microbial origin restore growth and normalize lipid
      absorption in a pig model with exocrine pancreatic insufficiency.
AB  - Introduction: The standard therapy for exocrine pancreatic insufficiency (EPI) is
      porcine-derived pancreatic enzyme replacement therapy (PERT). In the present
      study we tested a new approach with a mixture of pancreatic-like enzymes of
      microbial origin (PLEM) in a 1-week efficacy study in EPI pigs. In addition to
      the conventionally used coefficient of fat and nitrogen absorption (CFA and CNA),
      parameters that more accurately reflect the nutritional and health status, such
      as changes in the lipemic index (LI), plasma triglyceride (TG) and non-esterified
      fatty acid (NEFA) levels, and somatic growth, were determined. Material and
      methods: A PLEM dose containing 120 000 active lipase units, 80 000 active
      protease units and 12 000 active amylase units (all from Sigma, St. Louis, MO)
      was given as a powder, twice daily with a meal (40 g fat/meal) to 8 EPI pigs for
      7 days. Ten healthy pigs were used as a comparator. Results: The PLEM enhanced
      fat and protein digestion, and reversed growth impairment in EPI pigs. With
      treatment, CFA and CNA increased by 59% and 43% (p < 0.05), respectively.
      Although fat and protein absorption were lower than in the comparator, the
      postprandial blood lipid profile was normal as in healthy pigs. The mucosal
      thickness significantly increased by 27%, 50% and 26%, in the proximal, middle,
      and distal jejunum (p < 0.05) with treatment and resembled that of healthy
      animals. Conclusions: Pancreatic-like enzymes of microbial origin supported
      somatic growth and normalized the postprandial lipid profile. As a measure of
      efficacy, postprandial LI, TG and NEFA are viable endpoints to be explored in
      human trials.

PMID- 29593817
TI  - Identification of toxic metals in human embryonic tissues.
AB  - Introduction: The cause of a significant number of miscarriages remains
      unexplained. There is a need to identify the potential role of environmental,
      dietary and lifestyle factors in the risk of pregnancy loss. The present study
      was the first to investigate the content of miscarried embryonic material with
      respect to eight metals (aluminium, cadmium, chromium, copper, manganese, nickel,
      lead and zinc). Material and methods: Embryonic tissue samples (n = 20) were
      obtained from women undergoing misoprostol-induced removal of the embryo between
      the 6th and 9th week of gestation. The content of metals was analyzed using
      microwave-induced nitrogen plasma atomic emission spectrometry. Based on a short
      questionnaire, the smoking habits, dietary patterns and place of living of the
      investigated women were determined. Results: The general mean content of metals
      (MUg/g) decreased in the order copper (33.9) > manganese (24.7) > chromium (13.6)
      > zinc (13.3) > aluminium (6.5) > nickel (3.0) > lead (2.9) > cadmium (2.5).
      Profoundly increased concentrations (p < 0.05) of the toxic elements aluminium
      (over 5-fold), cadmium (over 2-fold) and lead (over 2-fold) were observed in
      samples obtained from former smoking women. The miscarried material in urban
      populations also revealed higher levels of cadmium (over 1.5-fold) and lead (over
      2-fold) compared to that obtained from women living in rural areas (p < 0.05). No
      associations with age or diet were found (p > 0.05). Conclusions: This study
      identified increased levels of aluminum, cadmium and lead in miscarried embryonic
      material and suggests some causative factors.

PMID- 29593819
TI  - Morphological and clinical aspects of the occurrence of accessory (multiple)
      renal arteries.
AB  - Renal vascularization variants vastly differ between individuals due to the very
      complex embryogenesis of the kidneys. Moreover, each variant may have
      implications for clinical and surgical interventions. The number of operating
      procedures continues to grow, and includes renal transplants, aneurysmorrhaphy
      and other vascular reconstructions. In any surgical technique, unawareness of the
      presence of multiple renal arteries may result in a fatal outcome, especially if
      laparoscopic methods are used. The aim of this review is to comprehensively
      identify the variation within multiple renal arteries and to highlight the
      connections between the presence of accessory renal arteries and the coexistence
      of other variants of vascularization. Another aim is to determine the potential
      clinical implications of the presence of accessory renal arteries. This study is
      of particular importance for surgeons, intervention radiologists, nephrologists
      and vascular surgeons.

PMID- 29593820
TI  - Prophylaxis of medial compartment gonarthrosis in varus knee - current state of
      knowledge.
AB  - The progression of gonarthrosis results in reduction of physical activity. One of
      the factors that increase the risk of osteoarthrosis may be joint overload
      related to the malalignment of the mechanical axis of the lower extremity. The
      medial compartment (MC) of the knee is particularly susceptible to overload due
      to the external knee adduction moment (EKAM). Varus knee malalignment contributes
      to increased EKAM and thus results in increased MC loading. The purpose of this
      study is to present methods described in current literature aimed at reducing the
      disproportion in the distribution of loads on articular surfaces of medial and
      lateral knee compartments in people with varus knee malalignment. Methods have
      been divided into non-surgical (gait training, physiotherapy, and orthopedic
      supplies such as valgus braces, lateral wedge insoles, walking poles) and
      surgical ones (corrective osteotomy).

PMID- 29593821
TI  - Myocarditis due to systemic lupus erythematosus associated with cardiogenic
      shock.

PMID- 29593818
TI  - Natural approaches in metabolic syndrome management.
AB  - Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk
      factors that raise the risk for heart disease and other health problems, such as
      diabetes mellitus and stroke. Treatment strategies include pharmacologic
      interventions and supplementary (or "alternative") treatments. Nutraceuticals are
      derived from food sources (isolated nutrients, dietary supplements and herbal
      products) that are purported to provide health benefits, in addition to providing
      basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases,
      improve health, delay the aging process, increase life expectancy, and support
      the structure and function of the body. The study of the beneficial effects of
      nutraceuticals in patients with MetS, including product standardization, duration
      of supplementation and definition of optimal dosing, could help better define
      appropriate treatment. This review focuses on widely marketed nutraceuticals
      (namely polyphenols, omega-3 fatty acids, macroelements and vitamins) with
      clinically demonstrated effects on more than one component of MetS.

PMID- 29593822
TI  - Giant coronary sinus secondary to partial anomalous pulmonary venous connection
      with combined mitral valve disease.

PMID- 29593823
TI  - Negative pressure wound therapy (NPWT) treatment of total supra-aortic
      debranching graft infection.

PMID- 29593824
TI  - Endoscopic necrosectomy through the major duodenal papilla under fluoroscopy
      imaging.

PMID- 29593825
TI  - Methotrexate-induced pancytopenia in a patient with ectopic pregnancy.

PMID- 29593826
TI  - Dangerous anaphylactic reaction to mustard.

PMID- 29593827
TI  - Preparation and applications of guard cell protoplasts from the leaf epidermis of
      Solanum lycopersicum.
AB  - Background: Guard cell protoplasts (GCPs) isolated from various plants have
      proven to be especially useful for studies of signal transduction pathways and
      plant development. But it is not easy to isolate highly purified preparations of
      large numbers of GCPs from plants. In this research, our focus is on a method to
      isolate large numbers of guard cells from tomato leaves. The protocols described
      yield millions of highly purified, viable GCPs, which are also suitable for
      studies on guard cell physiology. Results: We developed an efficient method for
      isolating GCPs from epidermal fragments of tomato leaves. The protocol requires a
      two-step digestion to isolate high-quality tomato GCPs. In this procedure,
      cellulysin (in method L) was replaced by cellulose "Onozuka" RS (in method S) in
      the first digestion step, which indicated that cellulase RS was more effective
      than cellulysin. Method S dramatically shortened the time required for obtaining
      high yields and high-quality GCPs. Moreover, according to the GCP yields,
      hydroponic plants were more effective than substrate-cultured plants.
      Conclusions: In this paper, protocols for large-scale preparation of GCPs and
      mesophyll cell protoplasts were described, followed by some success examples of
      their use in biochemical and molecular approaches such as reverse-transcription
      polymerase chain reaction, real-time polymerase chain reaction and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The method was proved to be a more
      efficient GCP-isolating method, capable of providing high yields with better
      quality in less time.

PMID- 29593829
TI  - 2017 and all that.

PMID- 29593828
TI  - Electrocardiogram Delineation in a Wistar Rat Experimental Model.
AB  - Background and Objectives: The extensive use of electrocardiogram (ECG)
      recordings during experimental protocols using small rodents requires an
      automatic delineation technique in the ECG with high performance. It has been
      shown that the wavelet transform (WT) based ECG delineator is a suitable tool to
      delineate electrocardiographic waveforms. The aim of this work is to implement
      and evaluate the ECG waves delineation in Wistar rats applying WT. We also
      describe the ECG signal of the Wistar rats giving the characteristics of its
      spectrum among other useful information. Methods: We evaluated a delineator based
      on WT in a Wistar rat electrocardiograms database which was annotated manually by
      experienced observers. Results: The delineation showed an "overall performance"
      such as sensitivity and a positive predictive value of 99.2% and 83.9% for P
      wave, 100% and 99.9% for QRS complex, and 100% and 99.8% for T-wave,
      respectively. We also compared temporal analysis based ECG delineator with the WT
      based ECG delineator in RR interval, QRS duration, QT interval, and T-wave peak
      to-end duration. The results showed that WT outperforms the temporal delineation
      technique in all parameters analyzed. Conclusions: Finally, we propose a WT based
      ECG delineator as a methodology to implement in a wide diversity of experimental
      ECG analyses using Wistar rats.

PMID- 29593830
TI  - Transcatheter Treatment of Functional Tricuspid Regurgitation Using the Trialign
      Device.
AB  - Functional tricuspid regurgitation (TR) represents an important unmet need in
      clinical cardiology given its prevalence, adverse prognostic impact and symptom
      burden associated with progressive right heart failure. Several transcatheter
      techniques are currently in early clinical testing to provide alternative
      treatment options for patients deemed unsuitable for tricuspid valve surgery.
      Amongst them, the TrialignTM device (Mitralign, Inc.) represents a novel
      percutaneous tricuspid valve annuloplasty technique, which aims to reduce
      tricuspid annular dilatation in functional TR by delivering and cinching two
      pledgeted sutures to the posterior portion of the tricuspid annulus via
      transjugular access. Early clinical data suggest the Trialign technique is safe
      and feasible, and associated with an improvement in quality-of-life measures.
      However, further studies are needed to confirm these data in larger cohorts of
      patients with longer follow up. In addition, future trials need to address the
      question whether TR reduction with the Trialign and other devices leads to an
      improvement in the patient's functional status and prognosis, over and above
      medical treatment alone.

PMID- 29593831
TI  - Minimally Invasive Surgical Mitral Valve Repair: State of the Art Review.
AB  - Minimally invasive surgical mitral valve repair (MVRepair) has become routine for
      the treatment of mitral valve regurgitation, and indications have been expanded
      to include reoperations. Current European Society of Cardiology/European
      Association for Cardio-Thoracic Surgery guidelines for the management of valvular
      heart disease recommended standards in terms of mitral valve disease
      differentiation, timing of intervention and surgical techniques to improve
      patient care. Numerous minimally invasive techniques to lessen the invasiveness
      have been described, such as the minimal-access J-sternotomy (ministernotomy),
      the parasternal incision, the port-access technique and the right
      minithoracotomy. Despite the development of catheter-based techniques, surgical
      repair remains the gold standard today for nearly all patients with degenerative
      valvular diseases and the majority of patients with other types of valvular
      diseases. Techniques include resection of the prolapsed segment, neo-chordae
      implantation and ring annuloplasty. In this review, the current indications for
      mitral valve surgery are summarised and state-of-the-art MVRepair techniques are
      highlighted.

PMID- 29593832
TI  - Bioprosthetic Valve Fracture During Valve-in-valve TAVR: Bench to Bedside.
AB  - Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) has been
      established as a safe and effective means of treating failed surgical
      bioprosthetic valves (BPVs) in patients at high risk for complications related to
      reoperation. Patients who undergo VIV TAVR are at risk of patient-prosthesis
      mismatch, as the transcatheter heart valve (THV) is implanted within the ring of
      the existing BPV, limiting full expansion and reducing the maximum achievable
      effective orifice area of the THV. Importantly, patient-prosthesis mismatch and
      high residual transvalvular gradients are associated with reduced survival
      following VIV TAVR. Bioprosthetic valve fracture (BVF) is as a novel technique to
      address this problem. During BPV, a non-compliant valvuloplasty balloon is
      positioned within the BPV frame, and a highpressure balloon inflation is
      performed to fracture the surgical sewing ring of the BPV. This allows for
      further expansion of the BPV as well as the implanted THV, thus increasing the
      maximum effective orifice area that can be achieved after VIV TAVR. This review
      focuses on the current evidence base for BVF to facilitate VIV TAVR, including
      initial bench testing, procedural technique, clinical experience and future
      directions.

PMID- 29593833
TI  - Understanding Neurologic Complications Following TAVR.
AB  - Transcatheter aortic valve replacement is a groundbreaking treatment modality for
      severe, symptomatic aortic stenosis. Despite the rapid progression in indications
      to include intermediate-risk patients, the risk of peri-procedural stroke
      remains, with a higher incidence rate than previously reported. Accurate
      assessment of peri-procedural stroke rates requires selection of careful and
      meaningful trial endpoints during evaluation of neuroprotective devices. In this
      article, we review recommendations and stroke definitions from academic research
      consortiums along with device trial results.

PMID- 29593834
TI  - Oral Anticoagulant Therapy for Early Post-TAVI Thrombosis.
AB  - While transcatheter aortic valve implantation (TAVI) is now the accepted
      treatment option of choice for patients presenting with severe symptomatic aortic
      stenosis who are deemed to be inoperable or of high surgical risk, there have
      been concerns regarding the risk of early valve failure and durability. One
      potential limitation is the occurrence of early post-TAVI thrombosis. Whilst the
      incidence of obstructive transcatheter heart valve (THV) thrombosis is <1 %, with
      technological advances in imaging, it is increasingly apparent that the overall
      true incidence is likely to be much higher with between 7-40 % of patients
      observed to have appearances strongly suggestive of asymptomatic subclinical THV
      thrombosis. This short review discusses the diagnosis of early THV thrombosis and
      the role of anticoagulation therapy for the management of these patients.

PMID- 29593835
TI  - Assessing the Risk of Leaflet Motion Abnormality Following Transcatheter Aortic
      Valve Implantation.
AB  - Leaflet motion abnormalities are a relatively new entity in the field of
      transcatheter aortic valve implantation and are associated with a range of
      different conditions, the extreme being prosthetic valve dysfunction with high
      gradients or central regurgitation and possibly early thrombotic degeneration.
      Another extreme condition is the incidental finding of leaflet thickening, but
      with normal transvalvular gradients. Transthoracic echocardiography is a useful
      screening tool for the detection of symptomatic thrombosis, but it has limited
      use in the detection of subclinical thrombosis and/or motion abnormalities alone.
      We, hereby, discuss the evidence for the potential screening process and
      subsequent management of those conditions associated with the leaflet motion
      abnormalities.

PMID- 29593836
TI  - Challenges in Patients with Diabetes: Improving Clinical Outcomes After
      Percutaneous Coronary Intervention Through EVOlving Stent Technology.
AB  - Patients with diabetes have poorer outcomes after percutaneous coronary
      intervention than patients without diabetes. The Cre8TM EVO drug-eluting stent
      (DES) has design features that aim to improve clinical outcomes in patients with
      diabetes. These include Abluminal Reservoir Technology - a proprietary polymer
      free drug-release system consisting of reservoirs on the abluminal surface of the
      stent that control drug release and direct the drug exclusively towards the
      vessel wall - and the AmphilimusTM drug formulation, which enables enhanced drug
      tissue permeation utilising fatty acid transport pathways. The latter is
      particularly advantageous in patients with diabetes, whose cell metabolism
      favours increased cellular uptake of fatty acid. Furthermore, evidence suggests
      that mTOR inhibitors (-limus drugs) utilised in conventional DES are less
      effective in diabetic cells. The new stent architecture provides high device
      deliverability and conformability, facilitating clinical use in complex disease
      patterns and high-risk lesion morphologies. Clinical evidence for the efficacy
      and safety of the Cre8TM DES in patients with diabetes has been demonstrated in a
      number of clinical trials and observational registries. These data are reviewed
      herein, along with an overview of on-going randomised trials.

PMID- 29593837
TI  - Is Complete Revascularisation Mandated for all Patients with Multivessel Coronary
      Artery Disease?
AB  - In multivessel coronary artery disease (MVCAD), myocardial revascularisation can
      be achieved by percutaneous coronary intervention (PCI) or coronary artery bypass
      grafting (CABG), with complete revascularisation on all diseased coronary
      segments or with incomplete revascularisation on selectively targeted lesions.
      Complete revascularisation confers a long-term prognostic benefit, but is
      associated with a higher rate of periprocedural events compared with incomplete
      revascularisation. In most patients with MVCAD, the main advantage of CABG over
      PCI is conferred by the achievement of more extensive revascularisation.
      According to current international guidelines, PCI is generally preferred in
      single-vessel disease, low-risk MVCAD or isolated left main disease; whereas CABG
      is usually recommended in patients with complex two-vessel disease, most patients
      with three-vessel disease and/or non-isolated left main disease. In patients with
      MVCAD, the choice on revascularisation modality should depend on a multifactorial
      evaluation, taking into account not only coronary anatomy, the ischaemic burden,
      myocardial function, age and the presence of comorbidities, but also the adequacy
      of myocardial revascularisation.

PMID- 29593838
TI  - B cell-based therapies in CNS autoimmunity: differentiating CD19 and CD20 as
      therapeutic targets.
AB  - Increasing recognition of the role of B cells in the adaptive immune response
      makes B cells an important therapeutic target in autoimmunity. Numerous current
      and developmental immunotherapies target B cells for elimination through
      recognition of cell-surface proteins expressed specifically on B cells, in
      particular CD19 and CD20. Similarities and differences in the function and
      expression of these two molecules predict some shared, and some distinct,
      pharmacological effects of agents targeting CD19 versus CD20, potentially leading
      to differences in the clinical safety and efficacy of such agents. Here, we
      review current knowledge of CD19 and CD20 function and biology, survey current
      and developmental therapies that target these molecules, and discuss potential
      differences in elimination of B cells by drugs that target CD19 versus CD20, with
      particular focus on the central nervous system autoimmune diseases multiple
      sclerosis and neuromyelitis optica. The principles and mechanisms herein
      discussed might also be relevant to a variety of other nervous system autoimmune
      disorders, including NMDA (N-methyl-D-aspartate) receptor encephalitis,
      transverse myelitis and myasthenia gravis.

PMID- 29593839
TI  - Optimal early active mobilisation protocol after extensor tendon repairs in zones
      V and VI: A systematic review of literature.
AB  - Introduction: Early mobilisation protocols after repair of extensor tendons in
      zone V and VI provide better outcomes than immobilisation protocols. This
      systematic review investigated different early active mobilisation protocols used
      after extensor tendon repair in zone V and VI. The purpose was to determine
      whether any one early active mobilisation protocol provides superior results.
      Methods: An extensive literature search was conducted to identify articles
      investigating the outcomes of early active mobilisation protocols after extensor
      tendon repair in zone V and VI. Databases searched were AMED, Embase, Medline,
      Cochrane and CINAHL. Studies were included if they involved participants with
      extensor tendon repairs in zone V and VI in digits 2-5 and described a post
      operative rehabilitation protocol which allowed early active metacarpophalangeal
      joint extension. Study designs included were randomised controlled trials,
      observational studies, cohort studies and case series. The Structured
      Effectiveness Quality Evaluation Scale was used to evaluate the methodological
      quality of the included studies. Results: Twelve articles met the inclusion
      criteria. Two types of early active mobilisation protocols were identified:
      controlled active motion protocols and relative motion extension splinting
      protocols. Articles describing relative motion extension splinting protocols were
      more recent but of lower methodological quality than those describing controlled
      active motion protocols. Participants treated with controlled active motion and
      relative motion extension splinting protocols had similar range of motion
      outcomes, but those in relative motion extension splinting groups returned to
      work earlier. Discussion: The evidence reviewed suggested that relative motion
      extension splinting protocols may allow an earlier return to function than
      controlled active motion protocols without a greater risk of complication.

PMID- 29593841
TI  - Bolstering the Three Pillars of the Essential Architecture of the Massage Therapy
      Profession: an Interview with Glenn M. Hymel, EdD, LMT.
AB  - As part of our interview editorial series, we bring forth a discussion with Dr.
      Glenn M. Hymel, the Founding Executive Editor of the International Journal of
      Therapeutic Massage and Bodywork. Dr. Hymel embodies the qualities set forth for
      the American Massage Therapy Association Dianne Polseno Lifetime Achievement
      Award, which he received in 2017. He has provided leadership and shown
      outstanding professionalism, and is a dedicated volunteer and a fervent advocate
      for research and education in the massage therapy profession. In this interview
      he discusses his massage therapy research, his interests, and his hopes for the
      future and the profession.

PMID- 29593840
TI  - Mediational Model of Multiple Sclerosis Impairments, Family Needs, and Caregiver
      Mental Health in Guadalajara, Mexico.
AB  - Individuals with multiple sclerosis (MS), especially those living in Latin
      America, often require assistance from family caregivers throughout the duration
      of the disease. Previous research suggests that family caregivers may experience
      positive and negative outcomes from providing care to individuals with MS, but
      few studies have examined the unmet needs of individuals providing care to family
      members with MS and how these unmet needs may mediate the relationship between MS
      symptoms and caregiver mental health. The current study examined the
      relationships among MS impairments (functional, neurological, cognitive,
      behavioral, and emotional), unmet family needs (household, informational,
      financial, social support, and health), and caregiver mental health (satisfaction
      with life, anxiety, burden, and depression) in a sample of 81 MS caregivers from
      Guadalajara, Mexico. A structural equation model demonstrated the mediational
      effect of unmet family needs on the relationship between MS impairments and
      caregiver mental health. These findings suggest that intervention research on MS
      caregivers in Latin America may consider focusing on caregiver mental health
      problems by addressing unmet family needs and teaching caregivers ways to manage
      the impairments of the individual with MS.

PMID- 29593842
TI  - Integration of Massage Therapy in Outpatient Cancer Care.
AB  - Background: Massage therapy can be helpful in alleviating cancer-related symptoms
      and cancer treatment-related symptoms. While surveys have noted that cancer
      patients seek out massage as a nonpharmacologic approach during cancer treatment,
      little is known about the integration of massage in outpatient cancer care.
      Purpose: The purpose of this study was to examine the extent to which massage is
      being integrated into outpatient cancer care at NCI-designated Cancer Centers.
      Setting: This study used descriptive methods to analyze the integration of
      massage in NCI-designated Cancer Centers providing clinical services to patients
      (n = 62). Design: Data were collected from 91.1% of the centers (n = 59) using
      content analysis and a telephone survey. A dataset was developed and coded for
      analysis. Main Outcome Measure: The integration of massage was assessed by an
      algorithm that was developed from a set of five variables: 1) acceptance of
      treatment as therapeutic, 2) institution offers treatment to patients, 3)
      clinical practice guidelines in place, 4) use of evidence-based resources to
      inform treatment, and 5) shared knowledge about treatment among health care team.
      All centers were scored against all five variables using a six-point scale, with
      all variables rated equally. Results: The integration of massage ranged from not
      at all (0) to very high (5) with all five levels of integration evident. Only 11
      centers (17.7% of total) rated a very high level of integration; nearly one-third
      of the centers (n = 22) were found to have no integration of massage at all-not
      even provision of information about massage to patients through the center
      website. Conclusions: The findings of this analysis suggest that research on
      massage is not being leveraged to integrate massage into outpatient cancer care.

PMID- 29593843
TI  - A Regional Analysis of U.S. Insurance Reimbursement Guidelines for Massage
      Therapy.
AB  - Introduction: Massage techniques fall within the scope of many different health
      care providers. Physical therapists, occupational therapists, and chiropractors
      receive insurance reimbursement for health care services, including massage.
      Although many patients pay out of pocket for massage services, it is unclear how
      the insurance company reimbursement policies factor provider qualifications into
      coverage. This project examined regional insurance reimbursement guidelines for
      massage therapy in relation to the role of the provider of massage services.
      Methods: A qualitative content analysis was used to explore guidelines for 26
      health insurance policies across seven US companies providing coverage in the
      northeastern United States. Publicly available information relevant to massage
      was obtained from insurance company websites and extracted into a dataset for
      thematic analysis. Data obtained included practice guidelines, techniques, and
      provider requirements. Information from the dataset was coded and analyzed using
      descriptive statistics. Results: Of the policies reviewed, 23% explicitly stated
      massage treatments were limited to 15-minute increments, 19% covered massage as
      one part of a comprehensive rehabilitation plan, and 27% required physician
      prescription. Massage techniques mentioned as qualifying for reimbursement
      included: Swedish, manual lymphatic drainage, mobilization/manipulation,
      myofascial release, and traction. Chiropractors, physical therapists, and
      occupational therapists could directly bill for massage. Massage therapists were
      specifically excluded as covered providers for seven (27%) policies. Conclusion:
      Although research supports massage for the treatment of a variety of conditions,
      the provider type has not been separately addressed. The reviewed policies that
      served the Northeastern states explicitly stated massage therapists could not
      bill insurance companies directly. The same insurance companies examined
      reimbursement for massage therapists in their western U.S. state policies. Other
      health care providers were able to bill directly for massage services to
      companies that did not accept direct billing by massage therapists. The specific
      exclusion of massage therapists as eligible providers violates the Affordable
      Care Act's non-discriminatory provision. Massage therapists should continue to
      advocate for reimbursement privileges to spur wider acceptance of massage therapy
      in health care.

PMID- 29593844
TI  - Fertility Massage: an Unethical Practice?

PMID- 29593845
TI  - Cancer Screening Among U.S. Medicaid Enrollees with Chronic Comorbidities or
      Residing in Long-Term Care Facilities.
AB  - Background: Ensuring appropriate cancer screenings among low-income persons with
      chronic conditions and persons residing in long-term care (LTC) facilities
      presents special challenges. This study examines the impact of having chronic
      diseases and of LTC residency status on cancer screening among adults enrolled in
      Medicaid, a joint state-federal government program providing health insurance for
      certain low-income individuals in the U.S. Methods: We used 2000-2003 Medicaid
      data for Medicaid-only beneficiaries and merged 2003 Medicare-Medicaid data for
      dually-eligible beneficiaries from four states to estimate the likelihood of
      cancer screening tests during a 12-month period. Multivariate regression models
      assessed the association of chronic conditions and LTC residency status with each
      type of cancer screening. Results: LTC residency was associated with significant
      reductions in screening tests for both Medicaid-only and Medicare-Medicaid
      enrollees; particularly large reductions were observed for receipt of mammograms.
      Enrollees with multiple chronic comorbidities were more likely to receive
      colorectal and prostate cancer screenings and less likely to receive Papanicolaou
      (Pap) tests than were those without chronic conditions. Conclusions: LTC
      residents have substantial risks of not receiving cancer screening tests. Not
      performing appropriate screenings may increase the risk of delayed/missed
      diagnoses and could increase disparities; however, it is also important to
      consider recommendations to appropriately discontinue screening and decrease the
      risk of overdiagnosis. Although anecdotal reports suggest that patients with
      serious comorbidities may not receive regular cancer screening, we found that
      having chronic conditions increases the likelihood of certain screening tests.
      More work is needed to better understand these issues and to facilitate referrals
      for appropriate cancer screenings.

PMID- 29593846
TI  - New insights into Nod-like receptors (NLRs) in liver diseases.
AB  - Activation of inflammatory signaling pathways is of central importance in the
      pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis
      (NASH). Nod-like receptors (NLRs) are intracellular innate immune sensors of
      microbes and danger signals that control multiple aspects of inflammatory
      responses. Recent studies demonstrated that NLRs are expressed and activated in
      innate immune cells as well as in parenchymal cells in the liver. For example,
      NLRP3 signaling is involved in liver ischemia-reperfusion (I/R) injury and
      silencing of NLRP3 can protect the liver from I/R injury. In this article, we
      review the evidence that highlights the critical importance of NLRs in the
      prevalent liver diseases. The significance of NLR-induced intracellular signaling
      pathways and cytokine production is also evaluated.

PMID- 29593848
TI  - Saturated fatty acids bound to albumin enhance osteopontin expression and
      cleavage in renal proximal tubular cells.
AB  - Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the
      kidneys of diabetic animals and patients with nephropathy. An increase in urinary
      albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment
      to the proximal tubules in proteinuric kidney diseases including diabetic
      nephropathy. This study was designed to examine if FA overload could stimulate
      OPN expression and cleavage in renal tubule epithelial cells. OPN gene and
      protein expression was examined in the kidney of Zucker diabetic (ZD) rats and
      cultured proximal tubular cells exposed to either bovine serum albumin (BSA) or
      BSA conjugated with palmitic acid (PA), the most abundant saturated plasma FA.
      Real-time PCR analysis confirmed an upregulation of renal cortical OPN gene
      correlated with albuminuria and nephropathy progression in ZD rats at the age of
      7-20 weeks. Immunofluorescence staining of kidney sections revealed a massive
      induction of OPN protein in albumin-overloaded proximal tubules of ZD rats. A
      significant increase in both intact and cleaved OPN proteins was further
      demonstrated in the diabetic kidney and urine samples, which was attenuated by
      antiproteinuric treatment with losartan, an angiotensin II receptor blocker. When
      exposed to fatty acid-free BSA, NRK-52E cells exhibited an increase in protein
      levels of full-length and cleaved OPN. Moreover, the increase in OPN fragments
      was greatly enhanced in the presence of PA (250-500 uM). Together, our results
      support a stimulatory effect of albumin and conjugated FA on OPN expression and
      cleavage in renal tubule epithelial cells. Thus, besides lowering
      albuminuria/proteinuria, mitigating circulating FAs may be an effective
      intervention for preventing and slowing down the progression of nephropathy
      associated with obesity and type 2 diabetes.

PMID- 29593847
TI  - The crosstalk between autonomic nervous system and blood vessels.
AB  - The autonomic nervous system (ANS), comprised of two primary branches,
      sympathetic and parasympathetic nervous system, plays an essential role in the
      regulation of vascular wall contractility and tension. The sympathetic and
      parasympathetic nerves work together to balance the functions of autonomic
      effector organs. The neurotransmitters released from the varicosities in the ANS
      can regulate the vascular tone. Norepinephrine (NE), adenosine triphosphate (ATP)
      and Neuropeptide Y (NPY) function as vasoconstrictors, whereas acetylcholine
      (Ach) and calcitonin gene-related peptide (CGRP) can mediate vasodilation. On the
      other hand, vascular factors, such as endothelium-derived relaxing factor nitric
      oxide (NO), and constriction factor endothelin, play an important role in the
      autonomic nervous system in physiologic conditions. Endothelial dysfunction and
      inflammation are associated with the sympathetic nerve activity in the
      pathological conditions, such as hypertension, heart failure, and diabetes
      mellitus. The dysfunction of the autonomic nervous system could be a risk factor
      for vascular diseases and the overactive sympathetic nerve is detrimental to the
      blood vessel. In this review, we summarize findings concerning the crosstalk
      between ANS and blood vessels in both physiological and pathological conditions
      and hope to provide insight into the development of therapeutic interventions of
      vascular diseases.

PMID- 29593849
TI  - Ascorbic acid and sodium benzoate synergistically aggravates testicular
      dysfunction in adult Wistar rats.
AB  - BACKGROUND: The effect of the concomitant use of sodium benzoate (NaB) and
      ascorbic acid on human health remains controversial. Therefore, the current study
      is designed to investigate the effect of NaB and ascorbic acid on the testicular
      function of adult Wistar rats. METHODS: Adult Wistar rats were randomly allotted
      into Control (vehicle; received 1 ml of distilled water), NaB-treated (SB
      treated; received 100 mg/kg body weight; b.w), ascorbic acid-treated (AA-treated;
      received 150 mg/kg b.w) and NaB+ ascorbic acid-treated (SB+AA-treated) groups.
      The treatment lasted for 28 days and the administration was given orally. The
      body weight change was monitored. Semen analysis, biochemical assay and
      histological examination were performed. RESULTS: Treatment with NaB
      significantly altered the cytoarchitecture of testicular tissue, sperm quality,
      testicular endocrine function and oxidative stress status without any alteration
      in body weight gain compared to control. In addition, treatment with NaB+
      ascorbic acid exacerbated testicular tissue disruption, impaired sperm quality
      and testicular endocrine impairment with significant reduction in oxidative
      stress and unaltered body weight gain when compared with NaB-treated group.
      CONCLUSION: This study suggests that ascorbic acid and NaB synergistically
      aggravates testicular dysfunction. This is independent of oxidative stress
      status.

PMID- 29593850
TI  - Systemic delivery of selective EP1 and EP3 receptor antagonists attenuates
      pentylenetetrazole-induced seizures in mice.
AB  - Neuroinflammation plays a major role in brain excitability and may contribute to
      the development of epilepsy. Prostaglandin E2 (PGE2) is a direct mediator of
      inflammatory responses and, through EP receptors, plays an important role in
      neuronal excitability. Pharmacological evidence supports that centrally
      administered EP1 and EP3 receptor antagonists reduced acutely evoked seizures in
      rats. Translation of these findings would benefit from evidence of efficacy with
      a more clinically relevant route of delivery and validation in another species.
      In the current study we investigated whether the systemic administration of EP1
      and EP3 agonists and antagonists modulate pentylenetetrazole (PTZ)-induced
      seizures in mice. In addition, it was examined whether these compounds alter Na+,
      K+-ATPase activity, an enzyme responsible for the homeostatic ionic equilibrium
      and, consequently, for the resting membrane potential in neurons. While the
      systemic administration of EP1 and EP3 antagonists (ONO-8713 and ONO-AE3-240,
      respectively) attenuated, the respective agonists (ONO-DI-004 and ONO-AE-248)
      potentiated PTZ-induced seizures (all compounds injected at the dose of 10 ug/kg,
      s.c., 30 min before PTZ challenge). Co-administration of either EP1 or EP3
      agonist with the respective antagonists nullified the anticonvulsant effects of
      EP1/3 receptor blockade. In addition, EP1 and EP3 agonists exacerbated PTZ
      induced decrease of Na+, K+-ATPase activity in both cerebral cortex and
      hippocampus, whereas, EP1 and EP3 antagonists prevented PTZ-induced decrease of
      Na+, K+-ATPase activity in both structures. Our findings support and extend
      evidence that EP1 and EP3 receptors may be novel targets for the development of
      anticonvulsant drugs.

PMID- 29593852
TI  - Ideological Responses to the EU Refugee Crisis: The Left, the Right, and the
      Extremes.
AB  - The 2016 European Union (EU) refugee crisis exposed a fundamental distinction in
      political attitudes between the political left and right. Previous findings
      suggest, however, that besides political orientation, ideological strength (i.e.,
      political extremism) is also relevant to understand such distinctive attitudes.
      Our study reveals that the political right is more anxious, and the political
      left experiences more self-efficacy, about the refugee crisis. At the same time,
      the political extremes-at both sides of the spectrum-are more likely than
      moderates to believe that the solution to this societal problem is simple.
      Furthermore, both extremes experience more judgmental certainty about their
      domain-specific knowledge of the refugee crisis, independent of their actual
      knowledge. Finally, belief in simple solutions mediated the relationship between
      ideology and judgmental certainty, but only among political extremists. We
      conclude that both ideological orientation and strength matter to understand
      citizens' reactions to the refugee crisis.

PMID- 29593851
TI  - Acupuncture for alcohol use disorder.
AB  - Alcohol use disorder (AUD) is a common medical and social problem, affecting
      about 240 million people in the world. To address this major health concern, the
      currently available treatments for AUD need to be improved. Acupuncture, a
      popular form of complementary and alternative therapy, is emerging as an
      effective treatment for AUD. This review summarizes how preclinical and clinical
      studies are related to the application of acupuncture for AUD. These studies
      suggest that if used correctly, acupuncture may effectively reduce alcohol
      intake, attenuate alcohol withdrawal syndrome, and rebalance AUD-induced
      maladaptation in neurotransmitters and hormones in related brain areas. The
      progress of research in this field is at an early stage. Future investigations
      with rigorous design and carefully constructed protocols are still needed.

PMID- 29593853
TI  - Complex cytogeographical patterns reveal a dynamic tetraploid-octoploid contact
      zone.
AB  - The distribution of cytotypes in mixed-ploidy species is crucial for evaluating
      ecological processes involved in the establishment and evolution of polyploid
      taxa. Here, we use flow cytometry and chromosome counts to explore cytotype
      diversity and distributions within a tetraploid-octoploid contact zone. We then
      use niche modelling and ploidy seed screening to assess the roles of niche
      differentiation among cytotypes and reproductive interactions, respectively, in
      promoting cytotype coexistence. Two cytotypes, tetraploids and octoploids, were
      dominant within the contact zone. They were most often distributed parapatrically
      or allopatrically, resulting in high geographic isolation. Still, 16.7 % of
      localities comprised two or more cytotypes, including the intermediate hexaploid
      cytotype. Tetraploids and octoploids had high environmental niche overlap and
      associated with similar climatic environments, suggesting they have similar
      ecological requirements. Given the geographical separation and habitat similarity
      among cytotypes, mixed-ploidy populations may be transitional and subject to the
      forces of minority cytotype exclusion which lead to pure-ploidy populations.
      However, seed ploidy analysis suggests that strong reproductive barriers may
      enforce assortative mating which favours stable cytotype coexistence. High
      cytogenetic diversity detected in the field suggests that unreduced gamete
      formation and hybridization events seem frequent in the studied polyploid complex
      and might be involved with the recurrent polyploid formation, governing, as well,
      the gene flow between cytogenetic entities.

PMID- 29593854
TI  - Expansive reed populations-alien invasion or disturbed wetlands?
AB  - The tall-statured grasses in the genus Phragmites are dominant vegetation in
      wetlands worldwide and thus play a vital role in ecosystem functioning. As a
      result, Phragmites spp. are some of the most widely studied plants; particularly
      in areas where changes to their abundances have occurred, most notably in Europe
      and North America. In southern Africa a pattern of reed expansion has occurred in
      recent decades that has shown a similar trend to cryptic invasions reported in
      North America. This study used molecular techniques to explore the phylogeography
      of P. australis and P. mauritianus in the region to investigate whether the
      expansion is due to an alien invasion or local factors such as wetland
      disturbance. Three haplotypes were found and all haplotypes are presently
      considered African haplotypes (haplotype K for P. australis and haplotype V and
      AP for P. mauritianus). Both Phragmites spp. were found to have high genetic
      diversity. Microsatellite and grass-waxy analysis also found evidence of
      hybridization between the two species. No evidence was found for a recent cryptic
      invasion of non-native haplotypes in southern Africa. The expansion of P.
      australis and P. mauritianus is therefore most likely a result of anthropogenic
      activity. Identifying and mitigating the human-mediated factors that may be
      contributing to reed growth, such as eutrophication and sedimentation, should be
      the focus of future management protocols.

PMID- 29593855
TI  - Novel 3D geometry and models of the lower regions of large trees for use in
      carbon accounting of primary forests.
AB  - There is high uncertainty in the contribution of land-use change to anthropogenic
      climate change, especially pertaining to below-ground carbon loss resulting from
      conversion of primary-to-secondary forest. Soil organic carbon (SOC) and coarse
      roots are concentrated close to tree trunks, a region usually unmeasured during
      soil carbon sampling. Soil carbon estimates and their variation with land-use
      change have not been correspondingly adjusted. Our aim was to deduce allometric
      equations that will allow improvement of SOC estimates and tree trunk carbon
      estimates, for primary forest stands that include large trees in rugged terrain.
      Terrestrial digital photography, photogrammetry and GIS software were used to
      produce 3D models of the buttresses, roots and humus mounds of large trees in
      primary forests dominated by Eucalyptus regnans in Tasmania. Models of 29, in
      situ eucalypts were made and analysed. 3D models of example eucalypt roots,
      logging debris, rainforest tree species, fallen trees, branches, root and trunk
      slices, and soil profiles were also derived. Measurements in 2D, from earlier
      work, of three buttress 'logs' were added to the data set. The 3D models had high
      spatial resolution. The modelling allowed checking and correction of field
      measurements. Tree anatomical detail was formulated, such as buttress shape,
      humus volume, root volume in the under-sampled zone and trunk hollow area. The
      allometric relationships developed link diameter at breast height and ground
      slope, to SOC and tree trunk carbon, the latter including a correction for
      senescence. These formulae can be applied to stand-level carbon accounting. The
      formulae allow the typically measured, inter-tree SOC to be corrected for not
      sampling near large trees. The 3D models developed are irreplaceable, being for
      increasingly rare, large trees, and they could be useful to other scientific
      endeavours.

PMID- 29593856
TI  - Seed dormancy and germination vary within and among species of milkweeds.
AB  - Pollinators in general and monarch butterflies in particular are in decline due
      to habitat loss. Efforts to restore habitats for insects that rely on specific
      plant groups as larvae or adults depend on the ability of practitioners to grow
      and produce these plants. Monarch larvae feed exclusively on milkweed species,
      primarily in the genus Asclepias, making propagation and restoration of these
      plants crucial for habitat restoration. Seed germination protocols for milkweeds
      are not well established, in part due to the large number of milkweed species and
      conflicting reports of seed dormancy in the genus. We tested for seed dormancy
      and the optimum period of cold stratification in 15 populations of A. speciosa
      and 1-2 populations of five additional species, including A. asperula, A.
      fascicularis, A. subulata, A. subverticillata and A. syriaca. We exposed seeds to
      cold (5  degrees C) moist conditions for 0, 2, 4, 6 and 8 weeks and then moved
      them to 15  degrees C/25  degrees C alternating temperatures. In A. speciosa,
      dormancy was detected in eight populations, and this dormancy was broken by 2-4
      weeks of cold stratification. The remaining seven populations showed no dormancy.
      Seed dormancy was also detected in two populations of A. fascicularis (broken by
      4-6 weeks of cold stratification) and a single population of A. syriaca (broken
      by 2 weeks of cold stratification). No dormancy was detected in A. asperula, A.
      subulata or A. subverticillata. Seed dormancy appears to be widespread in the
      genus (confirmed in 15 species) but can vary between populations even within the
      same species. Variation in seed dormancy and cold stratification requirements
      within and among Asclepias species suggests local adaptation and maternal
      environments may drive seedling ecology, and that growers should watch for low
      germination and use cold stratification as needed to maximize seed germination
      and retain genetic variability in restored populations.

PMID- 29593857
TI  - Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar
      Emetic in Pegylated Liposomes in BALB/c Mice Liver.
AB  - Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its
      use was discontinued due to high toxicity. Association of TE with liposomes is a
      strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower
      rates of uptake by macrophages and prolonged circulation compared to their
      nonpegylated counterparts. However, repeated administration of Lpeg can cause an
      Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by
      antibodies results in faster phagocytosis. This work evaluated the effect of TE
      administration on histopathological aspects and the effect of the ABC phenomenon
      on targeting and toxicity in mice. Our results show that treatment with free or
      liposomal TE had no effect on the erythrocyte count, on liver and spleen weight,
      and on hepatic, splenic, and cardiac histology in mice. Severe lesions were
      observed on the kidneys of animals treated with a single dose of free TE.
      Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant
      increase in Sb level in the liver without toxicity. Furthermore, mice treated
      with TE in liposomes showed normal renal histopathology. These results suggest
      site-specific targeting of Sb to the liver after induction of ABC phenomenon with
      no toxicity to other organs.

PMID- 29593858
TI  - Chicken Coccidiosis in Central Java, Indonesia: A Recent Update.
AB  - Avian coccidiosis is a huge problem worldwide. Heavily infected animals that show
      severe clinical signs and coccidiostat resistance are causing important economic
      losses. The present study aimed to update the recent cases of coccidiosis in
      Central Java, Indonesia, and to show the importance of the disease in the region.
      A total of 699 samples were obtained from different chicken breed. Different
      Eimeria species were detected in 175 individuals (25.04%). Three different groups
      of chicken breed were considered: local chicken (autochthonous chickens of Sentul
      and Jawa), commercial broiler, and layer. Broiler chickens showed the highest
      prevalence of infection (34%), followed by layer (26.26%) and local chickens
      (10.45%). Mild to severe clinical signs of avian coccidiosis were observed in 42%
      of the infected animals, while 58% of the infected animals showed no clinical
      signs other than low feed conversion rates. Seven different Eimeria species were
      identified: E. tenella was the most prevalent (43.3%), followed by E. maxima
      (26.3%), E. necatrix (15.7%), E. acervulina (8%), E. praecox (3.1%), E. mitis
      (2.2%), and E. brunetti (1.3%). Coinfections with several Eimeria species were
      diagnosed. With this study we found massive usage of coccidiostat in the region
      even though its usage cannot guarantee coccidiosis-free chicken production.

PMID- 29593860
TI  - Potential drug-drug interactions with direct oral anticoagulants in elderly
      hospitalized patients.
AB  - Background: To determine the prevalence and nature of potential drug-drug
      interactions (DDIs) with direct oral anticoagulants (DOACs) in elderly
      hospitalized patients. Methods: This was a retrospective observational study.
      Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or
      dabigatran; and admitted to the Repatriation General Hospital between April 2014
      and July 2015. A list of clinically relevant 'perpetrator' drugs was compiled
      from product information, the Australian Medicines Handbook, the Australian
      National Prescribing Service resources, and local health network guidelines. The
      prevalence and nature of potential DDIs with DOACs was determined by comparing
      inpatient drug charts with the list of perpetrator drugs. Results: There were 122
      patients in the study with a mean age of 82 years. Most patients had nonvalvular
      atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%).
      Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients
      had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti
      inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had
      potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking
      drugs that increase DOAC plasma concentrations (amiodarone, erythromycin,
      diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC
      plasma concentrations (carbamazepine, primidone or phenytoin). There were no
      cases of patients taking contraindicated interacting drugs. Discussion: Potential
      DDIs with DOACs in elderly hospital inpatients are relatively common,
      particularly interactions that may increase the risk of bleeding. The risk
      benefit ratio of DOACs in elderly patients on polypharmacy should always be
      carefully considered.

PMID- 29593861
TI  - Excipient of medication the probable cause of urticaria in a boy with autism.

PMID- 29593859
TI  - A threshold trajectory was revealed by isolating the effects of hemoglobin rate
      of rise in anemia of chronic kidney disease.
AB  - Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of
      rise (RoR) in chronic kidney disease (CKD) patients with anemia who have
      initiated therapy with erythropoiesis stimulating agents (ESAs). Methods:
      Observational cohort of CKD patients initiating ESA therapy from the
      Centricity(r) database, 1990-2011. Proportional hazards models tested the
      hypothesis that a slower Hb RoR (0 < g/dl/month ? 0.125) is associated with a
      lower cardiovascular (CV) incidence [composite of fatal/nonfatal myocardial
      infarction (MI) and stroke] compared with faster RoR (0.125 < g/dl/month ? 2.0,
      and >2.0 g/dl/month). Results: A total of 9220 patients receiving ESAs were
      followed for an average of 3.1 years. Slow (group B) RoR versus medium (group C')
      and fast (group D') RoR in Hb, throughout all Hb milestones, was associated with
      lower risk of the composite endpoint [B (slow) versus D' (fast) [hazard ratio
      (HR) = 0.20 (0.11, 0.39), p < 0.0001]; B versus C' (medium) [HR = 0.34 (0.19,
      0.62), p = 0.0004], and C' versus D' [HR = 0.60 (0.42, 0.85), p = 0.005]]. Within
      achieved Hb milestones, HRs were: B versus D' at milestone ? 14.1 g/dl [HR = 0.17
      (0.05, 0.56); p = 0.004] and at milestone 12.6-14.0 [HR = 0.18 (0.07, 0.46), p =
      0.0004]. Conclusion: Rapid Hb rise is associated with adverse CV outcomes, with
      markedly lower risk for rates below a threshold trajectory of 0.125 g/dl/month,
      even with complete correction.

PMID- 29593862
TI  - Surgical removal of fibrous axillary seroma pocket and closing of dead space
      using a lattisimus dorsi flap.
AB  - Seroma formation after axillary dissection is a common problem in breast cancer
      surgery. We report the case of a 68-year-old female with breast cancer who
      underwent a wide local excision and axillary clearance due to stage III breast
      cancer. Patient received post-operative whole breast irradiation therapy and
      developed a painful, infected seroma one month after surgery. This was treated
      with antibiotic therapy after which the infection subsided. One year after
      surgery patient presented with a painful persisting seroma in the left axilla. We
      decided to surgically treat the seroma by removing the fibrous seroma capsula and
      closing of the dead space with a latissimus dorsi flap. Six weeks after surgery,
      patient was pain and seroma free and was happy with the surgical result.
      Latissimus dorsi flap harvesting is an ideal way to treat persisting fibrous
      encapsulated seroma pockets after axillary clearance in the treatment of breast
      cancer.

PMID- 29593863
TI  - Peritoneal encapsulation as a cause of chronic recurrent abdominal pain in a
      young male.
AB  - This case report describes an otherwise well 20-year-old male who presented to
      hospital with vague, long-standing abdominal symptoms and was found to have
      peritoneal encapsulation.

PMID- 29593864
TI  - Laparoscopic abdominoperineal resection for the treatment of a mucinous
      adenocarcinoma associated with an anal fistula.
AB  - Mucinous adenocarcinoma associated with an anal fistula is a rare oncologic
      entity which may pose diagnostic and therapeutic challenges for Surgeons and
      Medical Oncologists. Few reported cases without definite therapeutic guidelines
      exist. It represents 2-3% of all gastrointestinal malignancies and arises from
      chronic anal fistulas, ischiorectal or perianal abscesses. We report a case of
      perianal mucinous adenocarcinoma in a 65-year-old male initially surgically
      treated multiple times for a recurrent fistula in ano of 5 years duration. He
      presented with an ischiorectal and a perianal fistula. Incisional biopsy from
      fistulotomy revealed mucinous adenocarcinoma. Contrast enhanced computed
      tomography scan and magnetic resonance imaging showed a localized perianal growth
      of a tumor which was further evaluated with colonoscopy. With no evidence of
      metastasis, we performed a laparoscopic abdominoperineal resection (APR). Two
      years follow-up after APR and without adjuvant chemotherapy there is not any
      evidence of recurrence or distant metastasis.

PMID- 29593865
TI  - A report of rare adverse tissue reaction to Ethilon(r) Nylon Suture.
AB  - This report describes a rare severe tissue reaction, as demonstrated in clinical
      photographs, to nylon sutures and illustrates how simple immediate removal of
      sutures isolates the irritant stimulus and results in rapid resolution, without
      the risk, cost and inconvenience of antibiotic treatment.

PMID- 29593866
TI  - A rare case of giant extra-ovarian mucinous cystadenoma arising from sigmoid
      mesocolon.
AB  - An 80-year-old female presented with one month history of acutely worsening
      abdominal distention and pain, without features of bowel obstruction. A giant
      intra-abdominal simple cyst, separate from the ovaries, was seen on imaging.
      Initial haematological and biochemical investigations, including tumour markers,
      were normal. At laparotomy, the cystic tumour was discovered to arise from the
      sigmoid mesocolon and was resected en bloc. Histopathology revealed the tumour to
      be a benign extra-ovarian mucinous cystadenoma, which is a neoplasm of ovarian
      origin that can arise from extra-ovarian sites, including the mesentery. Extra
      ovarian mucinous cystadenoma arising specifically from the mesentery are very
      rare intra-abdominal neoplasms with malignant potential despite its benign
      appearance on investigations. This case aims to raise awareness of this condition
      and to highlight its diagnostic approach and surgical management.

PMID- 29593867
TI  - Joint hierarchical Gaussian process model with application to personalized
      prediction in medical monitoring.
AB  - A two-level Gaussian process (GP) joint model is proposed to improve personalized
      prediction of medical monitoring data. The proposed model is applied to jointly
      analyze multiple longitudinal biomedical outcomes, including continuous
      measurements and binary outcomes, to achieve better prediction in disease
      progression. At the population level of the hierarchy, two independent GPs are
      used to capture the nonlinear trends in both the continuous biomedical marker and
      the binary outcome, respectively; at the individual level, a third GP, which is
      shared by the longitudinal measurement model and the longitudinal binary model,
      induces the correlation between these two model components and strengthens
      information borrowing across individuals. The proposed model is particularly
      advantageous in personalized prediction. It is applied to the motivating clinical
      data on cystic fibrosis disease progression, for which lung function measurements
      and onset of acute respiratory events are monitored jointly throughout each
      patient's clinical course. The results from both the simulation studies and the
      cystic fibrosis data application suggest that the inclusion of the shared
      individual-level GPs under the joint model framework leads to important
      improvements in personalized disease progression prediction.

PMID- 29593868
TI  - Recommendations for active correction of hypernatremia in volume-resuscitated
      shock or sepsis patients should be taken with a grain of salt: A systematic
      review.
AB  - Background: Healthcare-acquired hypernatremia (serum sodium >145 mEq/dL) is
      common among critically ill and other hospitalized patients and is usually
      treated with hypotonic fluid and/or diuretics to correct a "free water deficit."
      However, many hypernatremic patients are eu- or hypervolemic, and an evolving
      body of literature emphasizes the importance of rapidly returning critically ill
      patients to a neutral fluid balance after resuscitation. Objective: We searched
      for any randomized- or observational-controlled studies evaluating the impact of
      active interventions intended to correct hypernatremia to eunatremia on any
      outcome in volume-resuscitated patients with shock and/or sepsis. Data sources:
      We performed a systematic literature search with studies identified by searching
      MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane
      Database of Systematic Reviews, ClinicalTrials.gov, Index-Catalogue of the
      Library of the Surgeon General's Office, DARE (Database of Reviews of Effects),
      and CINAHL and scanning reference lists of relevant articles with abstracts
      published in English. Data synthesis: We found no randomized- or observational
      controlled trials measuring the impact of active correction of hypernatremia on
      any outcome in resuscitated patients. Conclusion: Recommendations for active
      correction of hypernatremia in resuscitated patients with sepsis or shock are
      unsupported by clinical research acceptable by modern evidence standards.

PMID- 29593869
TI  - Do post-reproductive aged females promote maternal health? Preliminary evidence
      from historical populations.
AB  - Background and Objectives: Much literature argues that natural selection
      conserved menopause and longevity in women because those who stopped childbearing
      helped bolster daughters' fertility and reduce infant mortality among
      grandchildren. Whether the presence of grandmothers ever improved fitness
      sufficiently to affect longevity via natural selection remains controversial and
      difficult to test. The argument underlying the grandmother and associated
      alloparenting literature, however, leads us to the novel and testable prediction
      that the presence of older women in historical societies could have affected
      population health by reducing lethality associated with childbearing.
      Methodology: Using historical life table data from four societies (Denmark,
      England and Wales, France and Sweden), we test the hypothesis that death rates
      among women initiating childbearing declined when the societies in which they
      were embedded included unexpectedly high frequencies of older women. We use time
      series analysis to measure the extent to which the observed likelihood of death
      among women aged 20-24 differs from statistically expected values when the number
      of older women grows or declines. Results: In three of the four countries
      examined, we find an inverse relationship between the frequency of post
      reproductive females in the population and odds of mortality among females at the
      peak of childbearing initiation. Conclusions and Implications: Results suggest
      that the presence of older women in a population may enhance population health by
      reducing mortality among women who face high risk of maternal death, although
      additional research is needed to determine if this relationship is causal.

PMID- 29593870
TI  - Childhood food allergies: An evolutionary mismatch hypothesis.
AB  - For hominins living in the Paleolithic era, early food antigen exposures-in utero
      and throughout infancy-closely matched later exposures, and therefore immune
      system tolerance mechanisms evolved under the expectation of this condition being
      met. This predicts that the degree of mismatch between early and downstream food
      antigen exposures is a key variable underlying the development of childhood food
      allergies. Three historical periods are identified in which the degree of
      mismatch climbs from near zero to substantial, as we transition from one period
      to another. The first encompasses our long history as foragers; the second begins
      with the advent of farming and the third spans only the most recent two or three
      decades, and manifests from social changes driven largely by an explosion in
      access to information. Testable predictions are generated and evaluated in light
      of available evidence, and an approach for primary prevention of childhood food
      allergies is proposed.

PMID- 29593871
TI  - Impact of motorboats on fish embryos depends on engine type.
AB  - Human generated noise is changing the natural underwater soundscapes worldwide.
      The most pervasive sources of underwater anthropogenic noise are motorboats,
      which have been found to negatively affect several aspects of fish biology.
      However, few studies have examined the effects of noise on early life stages,
      especially the embryonic stage, despite embryo health being critical to larval
      survival and recruitment. Here, we used a novel setup to monitor heart rates of
      embryos from the staghorn damselfish (Amblyglyphidodon curacao) in shallow reef
      conditions, allowing us to examine the effects of in situ boat noise in context
      with real-world exposure. We found that the heart rate of embryos increased in
      the presence of boat noise, which can be associated with the stress response.
      Additionally, we found 2-stroke outboard-powered boats had more than twice the
      effect on embryo heart rates than did 4-stroke powered boats, showing an increase
      in mean individual heart rate of 1.9% and 4.6%, respectively. To our knowledge
      this is the first evidence suggesting boat noise elicits a stress response in
      fish embryo and highlights the need to explore the ecological ramifications of
      boat noise stress during the embryo stage. Also, knowing the response of marine
      organisms caused by the sound emissions of particular engine types provides an
      important tool for reef managers to mitigate noise pollution.

PMID- 29593872
TI  - Crossing boundaries in conservation physiology.

PMID- 29593873
TI  - Post-transplant lymphoproliferative disorder of the bladder in a lung transplant
      recipient.
AB  - Post-transplant lymphoproliferative disorder (PTLD) occurs in ~5% of solid organ
      and hematopoietic stem cell transplant recipients. We report a unique
      presentation of PTLD in the bladder of a lung transplant recipient. Our patient
      was a 62-year-old female who received a bilateral lung transplant for chronic
      obstructive pulmonary disease. She presented with fever, left-sided flank pain
      and foul-smelling urine consistent with urosepsis. An abdominal and pelvic
      computerized tomography revealed an irregular and nodular bladder wall thickening
      suspicious for urothelial neoplasm. Cystoscopy revealed multiple bladder masses
      and biopsy demonstrated non-Hodgkin lymphoma consistent with PTLD. She was
      treated with a reduction in immunosuppression followed by chemotherapy and
      achieved remission. PTLD in the lung transplant recipients has been described in
      the gut, respiratory tract, skin, liver and kidney but not in the bladder. This
      case highlights the need for maintaining a high clinical vigilance even when
      transplant recipients present with seemingly benign clinical complaints.

PMID- 29593874
TI  - Statin-induced rhabdomyolysis: a complication of a commonly overlooked drug
      interaction.
AB  - Rhabdomyolysis is a well-documented side effect of statin therapy. This risk is
      increased with concurrent use of medications that inhibit cytochrome p450-3A4
      (CYP3A4), such as macrolide antibiotics. We present the case of a 67-year-old
      patient who was commenced on clarithromycin on a background of simvastatin
      therapy, resulting in rhabdomyolysis. This case highlights the need for awareness
      of common drug interactions associated with statins. It also emphasizes the
      significance of commencing statins at a lower dose in new patients, and lastly,
      the importance of early recognition and management of rhabdomyolysis to prevent
      the development of complications.

PMID- 29593875
TI  - Long-term, low-dose of clarithromycin as a cause of community-acquired
      Clostridium difficile infection in a 5-year-old boy.
AB  - Clostridium difficile is one of the most common causes of antibiotic-associated
      diarrhoea. Despite C. difficile infection (CDI) has increased in all ages
      worldwide, episodes of CDI are often misdiagnosed due to the lack of clinical
      suspicion. Macrolides are also associated with CDI. Additionally, exposure to
      macrolides in the 12 weeks preceding infection is reported to be a significant
      risk factor of CDI in a child. We report here a 5-year-old Japanese boy who
      presented with acute onset of watery diarrhoea. He was diagnosed with community
      acquired CDI induced by long-term (20 weeks), low-dose, oral clarithromycin for
      otitis media with effusion, and he recovered by conservative treatment.
      Physicians should be more cautious of community-acquired CDI in children who take
      long-term, low-dose macrolides, not to misdiagnose as diarrhoea by its side
      effect, and avoid unnecessary use of systemic antibiotics.

PMID- 29593876
TI  - Life-threatening hemoptysis: case of Osler-Weber-Rendu Syndrome.
AB  - Hereditary haemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu
      syndrome, is a rare autosomal dominant vascular disorder. Patients with HHT may
      present with a wide spectrum of clinical manifestations, some considered to be
      life-threatening. We present the case of a 53-year-old male who presented with
      massive haemoptysis. Chest computed tomography scan was remarkable for a large
      anterior, left lower lobe arteriovenous malformation. The patient underwent a
      pulmonary angiogram with embolization of a large left lung arteriovenous
      malformation, which proved to be successful in controlling the bleeding.

PMID- 29593877
TI  - Refractory hyperparathyroidism with a T3 bony lesion-differential diagnoses.
AB  - We report a case of severe hyperparathyroidism complicated by osteitis fibrosa
      cystica in an 83-year-old man post-myocardial infarction. The lesions were
      evident on magnetic resonance imaging only. A diagnosis of parathyroid carcinoma
      was considered due to clinical appearance of the parathyroid intraoperatively and
      the presence of an invasive T3 lesion mimicking metastatic disease.
      Differentiating parathyroid carcinoma from the benign causes at presentation can
      be difficult due to overlapping clinical, biochemical, radiological and
      histological features. The presence of bony lesions increases the diagnostic
      complexity of the case and demonstrates the challenges involved in the management
      of this disorder.

PMID- 29593878
TI  - Methicillin-resistant Staphylococcus aureus prostatic abscess after traumatic
      rectal injury.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection of
      the skin, soft tissue, bones and heart. MRSA is a rarely reported organism of
      prostatic abscess (PA). We present a case of an intravenous drug user who
      presented with dyspareunia, dysuria and dyschezia after a traumatic injury to the
      rectum. He was diagnosed with PA, which was treated with transurethral resection
      of the prostate drainage and intravenous antibiotics. MRSA PA carries a low case
      fatality rate on early diagnosis and treatment with proper antibiotics with or
      without drainage of the abscess.

PMID- 29593879
TI  - The Role of Desmopressin in the Management of Severe, Hypovolemic Hyponatremia: A
      Single-Center, Comparative Analysis.
AB  - Background: The role of desmopressin (DDAVP) to prevent or treat rapid serum
      sodium concentration ([Na]s) correction during hyponatremia management remains
      unclear. Objective: To assess DDAVP use during the first 48 hours of severe,
      hypovolemic hyponatremia management. The primary study hypothesis was that the
      use of DDAVP would slow the rate of [Na]s correction compared with those not
      receiving DDAVP. Design: A retrospective, observational, comparison study.
      Setting: A single, Canadian, tertiary center. Patients: All admitted patients
      referred to the nephrology service for severe, hypovolemic hyponatremia ([Na]s <
      125 mmol/L) over a 12-month period from November 2015. Measurements: The primary
      outcomes measure was the [Na]s after medical management for 48 hours. The length
      of hospital stay was also measured. Methods: Patients were grouped based on
      whether they received DDAVP during the first 48 hours of treatment, and [Na]s
      correction was compared between groups using linear regression. An exploratory,
      multivariable, linear regression model was used to adjust for diabetes status,
      active malignancy, intensive care unit (ICU) admission, and hypertonic saline
      administration. Results: Twenty-eight patients were identified, with baseline
      mean [Na]s of 112.7 +/- 6.6 mmol/L versus 117 +/- 4.3mmol/L (P = .06) in those
      receiving (n = 16) and not receiving DDAVP (n = 12), respectively. The DDAVP
      group had a more rapid [Na]s correction on the first day compared with those not
      receiving DDAVP, 7.7 +/- 3.8 mmol/L/d versus 5.1 +/- 2.0 mmol/L/d (P = .04). On
      the second day, there was a similar rate of [Na]s correction between groups: 1.3
      +/- 4.3 mmol/L/d versus 2.6 +/- 3.2 mmol/L/d (P = .39), respectively. Overall,
      there was no difference in [Na]s correction after 48 hours between those who
      received DDAVP and those who did not: 121.7 +/- 7.5 mmol/L versus 124.8 +/- 5.7
      mmol/L (P = .24). Patients who had experienced an overcorrection were
      successfully treated with DDAVP (n = 5), so that no patient had an ongoing
      overcorrection by 48 hours. Limitations: The limited sample size and lack of
      randomization preclude definitive conclusion on the additional benefit of DDAVP
      to standard care. Conclusion: DDAVP appears to be safe and effective in the
      management of severe, hypovolemic hyponatremia, associated with similar [Na]s
      correction to those who did not receive DDAVP after 48 hours, despite an initial
      more rapid correction. A randomized trial should examine what benefit DDAVP
      confers in addition to standard care in the management of severe, hypovolemic
      hyponatremia.

PMID- 29593880
TI  - Atrophy of the putamen at time of clinical motor onset in Huntington's disease: a
      6-year follow-up study.
AB  - Background: Striatal atrophy is detectable many years before the predicted onset
      of motor symptoms in premanifest Huntington's disease (HD). However, the extent
      of these neurodegenerative changes at the actual time of conversion from
      premanifest to a motor manifest disease stage is not known. With this study, we
      aimed to assess differences in degree and rate of atrophy between converters,
      i.e. premanifest individuals who develop clinically manifest HD over the course
      of the study, and non-converters. Methods: Structural T1-weighted Magnetic
      Resonance Imaging (MRI) scans were used to measure volumes of seven subcortical
      structures. Images were acquired yearly over a maximum follow-up period of 6
      years (mean 4.8 +/- 1.8 years) in 57 participants (healthy controls n = 28,
      premanifest HD gene carriers n = 29). Of the premanifest HD gene carriers, 20
      individuals clinically developed manifest HD over the course of the study, i.e.
      converters, whereas 9 individuals did not show any clinical signs. Differences
      between controls, converters and non-converters in volumetric decline over time
      were assessed using a one-way ANCOVA with age, gender and intracranial volume as
      covariates. All data were adjusted for multiple comparisons using Bonferonni
      correction. Results: The putamen showed a significant difference in volume at the
      time of conversion in the converters group compared to the non-converters group
      (adjusted p = 0.04). Although, volumes of all other subcortical structures were
      smaller at time of conversion compared to non-converters and controls, these
      differences were not statistically significant. Over time, rate of volumetric
      decline in all subcortical structures in converters did not significantly differ
      from non-converters. Conclusions: Putamen volume is smaller at the time of
      manifestation of motor symptoms compared with premanifest HD that not showed any
      clinical disease progression during the course of this 6-year follow-up study.

PMID- 29593881
TI  - Clinical characteristics and patient-reported outcomes in patients with
      inadequately controlled rheumatoid arthritis despite ongoing treatment.
AB  - Background: Despite the wide array of treatments available for rheumatoid
      arthritis (RA), some patients continue to report unmet clinical needs. We
      investigated the extent of inadequate disease control in patients with RA.
      Methods: Data were drawn from the Adelphi 2014 RA Disease-Specific Program in
      France, Germany, Italy, Spain and the UK. Rheumatologists provided patient
      demographics, comorbidities, satisfaction with RA control and other clinical
      details. Patients reported their level of satisfaction and completed the EuroQoL
      5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment
      Questionnaire. Patients had been on their current therapy >=3 months and had 28
      joint disease activity scores (DAS28) reported. Adequately controlled (DAS28
      <=3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared
      using univariate tests. Results: Of 1147 patients, 74% were women, the mean age
      was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven
      percent of patients had inadequately controlled RA, whereas 73% had adequately
      controlled RA. Inadequately controlled patients were more affected clinically
      versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the
      current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares,
      respectively (all p<0.0001). Inadequately controlled patients had higher rates of
      depression (16% vs 5%; p<0.0001), worse health state, greater work and activity
      impairment, and lower satisfaction rates among the patients and their physicians
      than the adequately controlled cohort. Conclusion: RA was insufficiently
      controlled in over a quarter of patients despite their current therapy and this
      had a negative impact on the patients.

PMID- 29593882
TI  - Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve
      live-attenuated vaccine safety and efficacy.
AB  - During RNA virus replication, there is the potential to incorporate mutations
      that affect virulence or pathogenesis. For live-attenuated vaccines, this has
      implications for stability, as replication may result in mutations that either
      restore the wild-type phenotype via reversion or compensate for the attenuating
      mutations by increasing virulence (pseudoreversion). Recent studies have
      demonstrated that altering the mutation rate of an RNA virus is an effective
      attenuation tool. To validate the safety of low-fidelity mutations to increase
      vaccine attenuation, several mutations in the RNA-dependent RNA-polymerase (RdRp)
      were tested in the live-attenuated Venezuelan equine encephalitis virus vaccine
      strain, TC-83. Next generation sequencing after passage in the presence of
      mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to
      have decreased replication fidelity, while a second mutant, TC-83 4x displayed no
      change in fidelity, but shared many phenotypic characteristics with TC-83 3x.
      Both mutants exhibited increased, albeit inconsistent attenuation in an infant
      mouse model, as well as increased immunogenicity and complete protection against
      lethal challenge of an adult murine model compared with the parent TC-83. During
      serial passaging in a highly permissive model, the mutants increased in virulence
      but remained less virulent than the parent TC-83. These results suggest that the
      incorporation of low-fidelity mutations into the RdRp of live-attenuated vaccines
      for RNA viruses can confer increased immunogenicity whilst showing some evidence
      of increased attenuation. However, while in theory such constructs may result in
      more effective vaccines, the instability of the vaccine phenotype decreases the
      likelihood of this being an effective vaccine strategy.

PMID- 29593884
TI  - Immunotherapy of lung cancer.

PMID- 29593883
TI  - Qualitative assessment of a Context of Consumption Framework to inform regulation
      of cigarette pack design in the U.S.
AB  - INTRODUCTION: Researchers and regulators need to know how changes to cigarette
      packages can influence population health. We sought to advance research on the
      role of cigarette packaging by assessing a theory-informed framework from the
      fields of design and consumer research. The selected Context of Consumption
      Framework posits cognitive, affective, and behavioral responses to visual design.
      To assess the Framework's potential for guiding research on the visual design of
      cigarette packaging in the U.S., this study seeks to understand to what extent
      the Context of Consumption Framework converges with how adult smokers think and
      talk about cigarette pack designs. METHODS: Data for this qualitative study came
      from six telephone-based focus groups conducted in March 2017. Two groups
      consisted of lesbian, gay, and bisexual participants; two groups of participants
      with less than four years college education; one group of LGB and straight
      identity; and one group the general population. All groups were selected for
      regional, gender, and racial/ethnic diversity. Participants (n=33) represented
      all nine U.S. Census divisions. We conducted a deductive qualitative analysis.
      RESULTS: Cigarette package designs captured the participants' attention,
      suggested the characteristics of the product, and reflected (or could be
      leveraged to convey) multiple dimensions of consumer identity. Particular to the
      affective responses to design, our participants shared that cigarette packaging
      conveyed how the pack could be used to particular ends, created an emotional
      response to the designs, complied with normative expectations of a cigarette,
      elicited interest when designs change, and prompted fascination when unique
      design characteristics are used. CONCLUSIONS: Use of the Context of Consumption
      Framework for cigarette product packaging design can inform regulatory research
      on tobacco product packaging. Researchers and regulators should consider multiple
      cognitive, affective, and behavioral responses to cigarette pack design.

PMID- 29593885
TI  - High-profile studies frequently and repetitively present data on the same
      patients, particularly in immunotherapy studies.
AB  - Background: Traditionally, study results have been presented as abstracts at
      major scientific meetings at the conclusion of the analysis. Recently,
      presentations of studies in progress and updates to previously presented data
      have been allowed at major meetings. The frequency and implications of a single
      study being presented multiple times, particularly in high profile oral
      presentations, have not been fully evaluated. Methods: To identify studies
      presented multiple times, abstracts from an approximately 1-year period from
      international conferences for three major societies devoted largely or in part to
      lung cancer research were assessed (ASCO 2015, World Lung 2015, ESMO 2015 and
      ASCO 2016). Abstracts were selected in a two-step process. The first step was for
      subject matter based on keywords: non-small cell lung cancer (NSCLC), small cell
      lung cancer (SCLC) or immunotherapy. Searches differed slightly based on
      individual website functionality, with ASCO searched by track, World Lung by
      session and ESMO by individual abstract. In a second step, abstracts for which
      clinical outcome data was presented from a trial with an identifiable National
      Clinical Trial (NCT) number were selected. Immunotherapy abstracts that did not
      include the treatment of NSCLC or SCLC were excluded in the second step. Results:
      A total of 851 abstracts were identified that were related to NSCLC, SCLC or
      immunotherapy. Of these, 357 referred to a clinical trial. In total, 110 of 357
      (31%) described clinical trials that were presented multiple times (mean 2.75,
      range 2-7), and in 44 (12%), this occurred at the same conference. Of the 113
      oral presentations, 75 (66%) presented data from clinical trials, either as
      posters or oral presentations. Further, 35 of the 113 (31%) oral presentations
      presented data from clinical trials that had generated other oral presentations.
      Of the 16 unique clinical trials leading to multiple oral presentations, a
      variety of issues led to the duplicate presentations, including different cohorts
      of the same trial, biomarker analysis, analysis by one study variable, or simply
      updated data. Moreover, 107 of the 357 (30%) clinical trial abstracts pertained
      to immunotherapy, including 4 of the 16 clinical trials generating multiple oral
      presentations. Of the 16 trials generating multiple oral presentations, 11 (69%)
      lead to a full-length publication by July 2017, including all of those pertaining
      to immunotherapy. Conclusions: There is a pattern of multiple presentations of
      clinical trials, particularly in oral presentations, at major meetings. In most
      cases, data presented in subsequent oral presentations related entirely to
      patients whose data was presented in the previous oral presentation.

PMID- 29593886
TI  - Immunotherapy in surgically resectable non-small cell lung cancer.
AB  - Surgical resection is the mainstay of therapy for patients with resectable and
      operable early stage non-small cell lung cancer (NSCLC). Surgery alone yields an
      unacceptably high rate of lung cancer recurrence. The addition of chemotherapy to
      surgery as adjuvant or neoadjuvant treatment can improve survival rates by
      roughly 5% at 5 years. Recently, major advances in cancer immunotherapy have led
      to better outcomes for many patients with lung cancer. Monoclonal antibodies to
      programmed death 1 and its ligand are now approved for both first and second line
      treatment patients with metastatic lung cancer. In this review, we will outline
      the rationale and current research strategies investigating the role of
      immunotherapy in resectable NSCLC.

PMID- 29593887
TI  - Immunotherapy in treatment naive advanced non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small
      cell lung cancer (NSCLC) comprises approximately 85% of lung cancers and,
      unfortunately, more than half of these patients are diagnosed with metastatic
      disease. Platinum-based chemotherapy has for long been the standard frontline
      therapy for advanced disease. Despite remarkable advances in targeted therapy for
      a subset of patients harboring a driver mutation, the prognosis in the majority
      of the lung cancer population have not changed significantly. More recently,
      immunotherapy has drastically changed the treatment of NSCLC and have established
      a new treatment paradigm for these patients. Pembrolizumab is now the new
      mainstay first-line treatment for those with high-PD-L1 expression. However, many
      questions remain regarding how to sequence and combine these agents in the
      frontline setting. The optimal patient selection strategies are also unclear.
      High PD-L1 expression is associated with higher response rates, but even patients
      with low or absent PD-L1 expression benefit from these drugs. More recently,
      tumor mutational burden is been proposed as a potential predictive marker for
      response. This article will review the data regarding the usage of immunotherapy
      in treatment naive advanced NSCLC.

PMID- 29593888
TI  - Immunotherapy in previously treated non-small cell lung cancer (NSCLC).
AB  - Treatment with immunotherapy has made a significant impact in the outcomes for
      those individuals diagnosed with metastatic non-small cell lung cancer (NSCLC)
      and its use is currently an established treatment modality. In light of recent
      advances in immunotherapy, improved survival, particularly for patients with
      stage IV NSCLC, has been reported with durable and prolonged responses in a
      subset of patients. Immune check point inhibitors, which include nivolumab,
      pembrolizumab, and atezolizumab, are standard treatment options in the salvage
      setting. Nivolumab and atezolizumab are approved for patients regardless of
      programmed death-ligand 1 (PD-L1) expression, whereas pembrolizumab requires
      tumor PD-L1 expression at the cut-off >=1%. In this review, we will outline the
      clinical development of immunotherapy in previously treated NSCLC, current
      challenges and discuss novel treatment strategies.

PMID- 29593889
TI  - Immunotherapy combination strategies (non-chemotherapy) in non-small cell lung
      cancer.
AB  - Immune checkpoint inhibitors enhance the activation and antitumor activity of the
      immune system, resulting in durable response rates in a select group of patients.
      Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory
      interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors
      target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1)
      and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of
      T-cell effector function. These therapeutic drugs were originally evaluated in
      patients with metastatic melanoma before expansion to all tumor types, including
      non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors
      such as pembrolizumab have now received FDA approval in the first-line setting
      for patients with positive PD-L1 expression tumor types; however, only a portion
      of patients have shown objective and sustainable responses. To expand the number
      of patients with observed response to immunotherapeutic agents including patients
      with negative PD-L1 expression tumors, clinical trials are ongoing to assess the
      safety and efficacy of combination immune checkpoint inhibitors and combination
      immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors
      have been found to be a promising therapeutic drug class with sustainable
      response rates and a tolerable safety profile, and efforts continue to improve
      these drugs in patients with NSCLC.

PMID- 29593890
TI  - Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell
      lung cancer.
AB  - Lung cancer continues to be the leading cause of cancer death worldwide.
      Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a
      powerful treatment option for advanced lung cancer. The relative success of
      programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in
      metastatic disease have increased interest in expanding their use to earlier
      stage NSCLC. The complex and diverse nature of stage III disease also invites the
      incorporation of immunotherapy into treatment plans in both the neoadjuvant and
      consolidation settings. Currently available data of anti-PD-(L)1 therapies in
      stage III NSCLC are limited. However, interim results from two studies are
      encouraging: a phase II neoadjuvant nivolumab trial demonstrated early signals of
      efficacy, and the phase III PACIFIC trial of durvalumab recently showed
      significant improvement in progression-free survival (PFS). Preliminary results
      for the phase II DETERRED trial of durvalumab have also been reported. Many
      studies are testing anti-PD-(L)1 therapies in the neoadjuvant and consolidation
      settings for stage III NSCLC, and will be discussed. As these studies mature they
      may provide further treatment options in management of stage III NSCLC.

PMID- 29593891
TI  - Immune checkpoint inhibitors in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a rapidly progressive cancer that often
      debilitates patients within months of detection and quickly becomes refractory to
      the limited options of therapy. While SCLC is not generally considered an
      immunogenic tumor, clinical experience suggests that patients with robust immune
      response manifesting as paraneoplastic syndrome are more likely to present with
      limited stage of the disease and tend to have a better prognosis. Monoclonal
      antibodies targeting critical negative regulators of immune response, so called
      immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
      and programmed death 1 (PD-1) have expanded the application of immune-based
      therapies to increasing number of advanced stage cancers. These agents overcome
      the inhibitory immune signals leading to a heightened immune response against
      cancer cells. These immune checkpoint inhibitors have established efficacy
      leading to regulatory approval for their use in many cancer types including non
      small cell lung cancer (NSCLC). Evaluation of the CTLA-4 inhibitor, ipilimumab
      and PD-1 inhibitors, nivolumab and pembrolizumab in SCLC have shown encouraging
      signal but definitive studies are still ongoing. In this review, we discuss the
      rationale behind the use of checkpoint inhibitors in SCLC, contextualize the
      results of early trials of immunotherapy agents in SCLC and project the future
      evolution of this strategy.

PMID- 29593892
TI  - Combining radiation plus immunotherapy to improve systemic immune response.
AB  - Over the past decade, the fields of oncology have made great strides in
      therapies. The development of new therapeutics and increased understanding of the
      role of the immune system in the development and treatment of cancer has led to
      increased collaboration between oncologic fields. Recent technologic advancements
      in radiation therapy (RT), including stereotactic beam radiation therapy (SBRT),
      have improved local control and offer an alternative to surgery for the control
      of oligometastatic disease. Immunotherapy has proven a promising therapeutic in
      the treatment of metastatic disease but treatment resistance remains a
      significant obstacle in the majority of patients. Together, radiation and
      immunotherapy offer potential to eliminate metastatic disease, reduce time to
      recurrence and improve overall survival. Major obstacles to these positive
      outcomes include high tumor burden, intratumoral heterogeneity, and the negative
      effects of tumor stroma, to name a few. Multimodality treatments are under heavy
      investigation. Promising data from clinical trials is emerging to highlight the
      value of RT in combination with immunotherapy. However, the mechanisms behind
      their synergistic effects remain to be fully elucidated. This review aims to
      highlight the existing literature and offers hypotheses to explain mechanisms
      behind the synergy of RT and immunotherapy.

PMID- 29593893
TI  - Identifying and managing the adverse effects of immune checkpoint blockade.
AB  - Immunotherapy has revolutionized the field of oncology. By inhibiting the
      cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1)
      immune checkpoint pathways, multiple studies have demonstrated greatly improved
      survival in locally advanced and metastatic cancers including melanoma, renal,
      lung, gastric, and hepatocellular carcinoma. Trials in other malignancies are
      ongoing, and undoubtedly the number of drugs in this space will grow beyond the
      six currently approved by the Food and Drug Administration. However, by altering
      the immune response to fight cancer, a new class of side effects has emerged
      known as immune-related adverse events (irAEs). These adverse events are due to
      overactivation of the immune system in almost any organ of the body, and can
      occur at any point along a patient's treatment course. irAEs such as
      endocrinopathies (thyroiditis), colitis, and pneumonitis may occur more commonly.
      However, other organs such as the liver, heart, or brain may also be affected by
      immune overactivation and any of these side effects may become life threatening.
      This review presents an approach to promptly recognize and manage these
      toxicities, to hopefully minimize morbidity and mortality from irAEs.

PMID- 29593894
TI  - Validation of a Survey Questionnaire on Organ Donation: An Arabic World Scenario.
AB  - Objective: To validate a questionnaire for measuring factors influencing organ
      donation and transplant. Methods: The constructed questionnaire was based on the
      theory of planned behavior by Ajzen Icek and had 45 questions including general
      inquiry and demographic information. Four experts on the topic, Arabic culture,
      and the Arabic and English languages established content validity through review.
      It was quantified by content validity index (CVI). Construct validity was
      established by principal component analysis (PCA), whereas internal consistency
      was checked by Cronbach's Alpha and intraclass correlation coefficient (ICC).
      Statistical analysis was performed by SPSS 22.0 statistical package. Results:
      Content validity in the form of S-CVI/Average and S-CVI/UA was 0.95 and 0.82,
      respectively, suggesting adequate relevance content of the questionnaire. Factor
      analysis indicated that the construct validity for each domain (knowledge,
      attitudes, beliefs, and intention) was 65%, 71%, 77%, and 70%, respectively.
      Cronbach's Alpha and ICC coefficients were 0.90, 0.67, 0.75, and 0.74 and 0.82,
      0.58, 0.61, and 0.74, respectively, for the domains. Conclusion: The
      questionnaire consists of 39 items on knowledge, attitudes, beliefs, and
      intention domains which is valid and reliable tool to use for organ donation and
      transplant survey.

PMID- 29593895
TI  - Cross-Sectional Serological Survey of Human Fascioliasis in Canutama Municipality
      in Western Amazon, Brazil.
AB  - Background: Fascioliasis is an important parasitic disease. In the northern
      region of Brazil, a human parasite infection has been reported through a
      coprological survey. Eggs of Fasciola hepatica were found in fecal samples of 11
      individuals. Knowledge of the infection in animals or the presence of snails is
      necessary to address the possibility of the parasite cycle occurrence in that
      region. The aim of this study was to describe the transmission of human
      fascioliasis in Canutama, Amazonas, in Western Amazonia, Brazil. Methods:
      Serological (ELISA and Western Blot, WB) and parasitological analyses were
      carried out in humans. In addition, the presence of the intermediate snail host
      within the community was examined. Results: A total of 434 human samples were
      included in the study, of which 36 (8.3%) were reactive by ELISA and 8 (1.8%)
      were reactive by WB. Fasciola hepatica eggs were found in one human sample. The
      occurrence of the intermediated host was recorded and 31/43 specimens were
      identified as Lymnaea columella. Conclusion. Canutama constitutes a focus of
      transmission of human fascioliasis. This study describes the first serological
      survey for human fascioliasis, as well as its simultaneous occurrence in human
      hosts and possible intermediates performed in northern Brazil.

PMID- 29593896
TI  - Enteroparasites in Riverside Settlements in the Pantanal Wetlands Ecosystem.
AB  - Background: Intestinal parasites are a major source of health problems in
      developing countries, where socioeconomic, cultural, and environmental conditions
      contribute in maintaining the biological cycles of various parasites and
      facilitating their spread. The objective of this study, conducted in Corumba,
      Mato Grosso do Sul state, Brazil, was to investigate the occurrence of intestinal
      parasites in riverside communities in the South Pantanal wetlands and conduct
      educational interventions focused on health and environmental preservation.
      Method: In total, 196 stool samples were tested for parasites using the
      merthiolate-iodine-formaldehyde concentration (MIFC) technique and spontaneous
      sedimentation and educational activities were carried out. Results:
      Enteroparasite prevalence was 72% (65.6-78.2%; 95% CI). Of the 141 positive
      cases, monoparasitism was found in 34.7%, biparasitism in 23%, and polyparasitism
      in 14.3%. Entamoeba coli was the most frequent protozoan (70.2%). Among
      helminths, hookworms were the most prevalent. Enteroparasitosis prevalence did
      not differ for sex or place of abode but proved higher in individuals older than
      10 years. Conclusion: The high positivity rate for enteroparasites found for the
      communities stems from lack of sanitation and poor personal and environmental
      hygiene habits, indicating that effective health policies and educational
      interventions are needed to reduce the current risk levels.

PMID- 29593897
TI  - Serum Presepsin Levels Are Not Elevated in Patients with Controlled Hypertension.
AB  - Introduction: Hypertension (HT) is a common serious condition associated with
      cardiovascular morbidity and mortality. The pathogenesis of HT is multifactorial
      and has been widely investigated. Besides the vascular, hormonal, and
      neurological factors, inflammation plays a crucial role in HT. Many inflammatory
      markers such as C-reactive protein, cytokines, and adhesion molecules have been
      studied in HT, which supported the role of inflammation in the pathogenesis of
      HT. Presepsin (PSP) is a novel biomarker of inflammation. Therefore, the
      potential relationship between PSP and HT was investigated in this study.
      Methods: Forty-eight patients with controlled HT and 48 controls without HT were
      included in our study. Besides routine clinical and laboratory data, PSP levels
      were measured in peripheral venous blood samples from all the participants.
      Results: PSP levels were significantly lower in patients with HT than in controls
      (144.98 +/- 75.98 versus 176.67 +/- 48.12 pg/mL, p = 0.011). PSP levels were
      positively correlated with hsCRP among both the patient and the control groups (p
      = 0.015 and p = 0.009, resp.). However, PSP levels were not correlated with WBC
      among both groups (p = 0.09 and p = 0.67, resp.). Conclusions: PSP levels are not
      elevated in patients with well-controlled HT compared to controls. This result
      may be associated with anti-inflammatory effects of antihypertensive medicines.

PMID- 29593898
TI  - Role of Mast Cells in Oral Lichen Planus and Oral Lichenoid Reactions.
AB  - Introduction: Oral lichen planus (OLP) is a chronic T cell mediated disease of
      oral mucosa, skin, and its appendages with a prevalence of 0.5 to 2.6% worldwide.
      Oral lichenoid reactions (OLR) are a group of lesions with diverse aetiologies
      but have clinical and histological features similar to OLP, thereby posing a
      great challenge in differentiating both lesions. Mast cells are multifunctional
      immune cells that play a major role in the pathogenesis of lichen planus by
      release of certain chemical mediators. Increased mast cell densities with
      significant percentage of degranulation have been observed as a consistent
      finding in pathogenesis of oral lichen planus. Aim: The current study was aimed
      at quantifying the mast cells in histopathological sections of OLP and OLR
      thereby aiding a means of distinguishing these lesions. Materials and Methods:
      The study group involved 21 cases of oral lichen planus, 21 cases of oral
      lichenoid reactions, and 10 control specimens of normal buccal mucosa. All the
      cases were stained with Toluidine Blue and routine haematoxylin and eosin and the
      mast cells were quantified. Statistical Analysis Used: The results were analyzed
      using the Kruskal-Wallis test and an intergroup analysis was performed using Mann
      Whitney U test. Conclusion: The number of mast cells showed an increased value in
      oral lichen planus when compared to oral lichenoid reaction and thus an
      estimation of mast cells count could aid in distinguishing OLP from OLR
      histopathologically.

PMID- 29593899
TI  - Feasibility and Safety of Bariatric Surgery in High-Risk Patients: A Single
      Center Experience.
AB  - Introduction: Despite the feasibility and safety of bariatric procedures
      nowadays, high-risk patients with vast obesity and severe comorbidities
      demonstrate relatively high perioperative morbidity and mortality rates and,
      therefore, form a distinguished challenge for the bariatric surgeons. Methods: We
      retrospectively analyzed high-risk patients, who underwent bariatric surgery in
      University Hospital Leipzig between May 2012 and December 2016. High-risk
      patients were defined when (Bergeat et al., 2016) at least one of the following
      risk factors was met: age >= 70 years, body mass index (BMI) > 70 kg/m2, liver
      cirrhosis, end-organ failure, or immunosuppression by status after organ
      transplantation along with (Birkmeyer et al., 2010) at least two comorbidities
      associated with obesity. Our analysis included early postoperative complications.
      Results: A total of 25 high-risk obese patients were identified. All patients had
      a standardized postoperative management with a mean length of hospital stay of 4
      +/- 1.4 days. One patient required an operative revision due to a stapler line
      leak after sleeve gastrectomy. No other major postoperative complications
      occurred. Conclusion: Bariatric surgery for severe high-risk patients can be
      performed safely in high-volume centers following standardized procedures.

PMID- 29593900
TI  - The Palatability of Lopinavir and Ritonavir Delivered by an Innovative Freeze
      Dried Fast-Dissolving Tablet Formulation.
AB  - Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce
      patient adherence particularly in pediatric populations requiring oral
      consumption. This study examines the palatability of an innovative delivery
      mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving
      tablets (FDTs) containing a fixed-dose combination of lopinavir and ritonavir
      (LPV/r). Consumption patterns of solutions during brief-access and long-term
      testing and baby foodstuff consumption were analyzed to evaluate the orosensory
      detection and avoidance of placebo FDTs containing no LPV/r (FDT-) and FDTs
      containing LPV/r (FDT+). Rats showed no change in consumption patterns for the
      placebo FDT- compared with control solutions. Rats can detect but do not avoid
      FDT+ at body-weight-adjusted dosages in both brief-access (30-s) and long-term
      (23 h) consumption tests. There is an aversive response to concentrated doses of
      FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the
      strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce,
      banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was
      associated with the presence of LPV/r and not the FDT- formulation itself. The
      novel FDT formulation appears to be a palatable delivery mechanism for oral
      antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.

PMID- 29593901
TI  - Frequent Benign, Nontraumatic, Noninflammatory Causes of Low Back Pain in
      Adolescents: MRI Findings.
AB  - Introduction: Low back pain (LBP) is common in children and adolescents. There
      are many factors that cause LBP, including structural disorders, degenerative
      changes, Scheuermann's disease, fractures, inflammation, and tumors. Magnetic
      Resonance Imaging is the gold standard for diagnosing spinal abnormalities and is
      mandatory when neurological symptoms exist. The study focuses on common MRI
      findings in adolescents with persistent LBP, without history of acute trauma or
      evidence of either inflammatory or rheumatic disease. Materials and Methods:
      Eleven adolescents were submitted to thoracic and/or lumbar spine MRI due to
      persistent LBP. The protocol consisted of T1 WI, T2 WI, and T2 WI with FS, in the
      axial, sagittal, and coronal plane. Results: MRI revealed structural
      abnormalities (scoliosis and kyphosis) in 4/11 (36.36%); disc abnormalities and
      endplate changes were found on 11/11 (100%). Typical Scheuermann's disease was
      found in 3/11 (27.27%). Endplate changes were severe in Scheuermann's patients
      and mild to moderate in the remaining 8/11 (72.72%). Kyphosis was in all cases
      secondary to Scheuermann's disease. Disk bulges and hernias were found in 8/11
      (72.72%), all located in the lumbar spine. Conclusion: In adolescents with LBP,
      structural spinal disorders, degenerative changes, and Scheuermann's disease are
      commonly found on MRI; however, degenerative changes prevail.

PMID- 29593902
TI  - Confidence amongst Multidisciplinary Professionals in Managing Paediatric
      Rheumatic Disease in Australia.
AB  - Objective: Interprofessional collaboration is a crucial component of care for
      children with rheumatic disease. Interprofessional care, when delivered
      appropriately, prevents disability and improves long-term prognosis in this
      vulnerable group. Methods: The aim of this survey was to explore allied health
      professionals' and nurses' confidence in treating paediatric rheumatology
      patients. Results: Overall, 117 participants were recruited, 77.9% of
      participants reported being "not confident at all," "not confident," or "neutral"
      in treating children with rheumatic diseases (RD) despite 65.1% of participants
      reporting having treated >1 paediatric rheumatology case in the past month.
      Furthermore, 67.2% of participants felt their undergraduate education in
      paediatric rheumatology was inadequate. "Journals" or "texts books" were used by
      49.3% of participants as their primary source of continuing professional
      development (CPD) and 39.3% of participants indicated that they did not undertake
      any CPD related to paediatric rheumatology. Small group and online education were
      perceived to be potentially of "great benefit" for CPD. Conclusion: This paper
      highlights allied health professionals' and nurses' perceived inadequacy of their
      undergraduate education in paediatric RD and their low confidence in recognising
      and treating RD. Undergraduate and postgraduate education opportunities focusing
      on interprofessional collaboration should be developed to address this workforce
      deficiency.

PMID- 29593903
TI  - A Possible Link between Anxiety and Schizophrenia and a Possible Role of
      Anhedonia.
AB  - In the prodromal phase of schizophrenia, severe alterations of the visual
      appearance of the environment have been found, accompanied by a state of intense
      anxiety. The present study considers the possibility that these alterations
      really exist in the appearance of objects, but that healthy people do not see
      them. The image of the world that we see is continuously deformed and fragmented
      by foreshortenings, partial overlapping, and so on and must be constantly
      reassembled and interpreted; otherwise, it could change so much that we would
      hardly recognize it. Since pleasure has been found to be involved in visual and
      cognitive information processing, the possibility is considered that anhedonia
      (the reduction of the ability to feel pleasure) might interfere with the correct
      reconstruction and interpretation of the image of the environment and alter its
      appearance. The possibility is also considered that these alterations might make
      the environment hostile, might at times evoke the sensation of being trapped by a
      predator, and might be the cause of the anxiety that accompanies them. According
      to some authors, they might also induce delusional ideas, in an attempt to
      restore meaning in a world that has become chaotic and frightening.

PMID- 29593904
TI  - Self-Rated Health Trajectories among Married Americans: Do Disparities Persist
      over 20 Years?
AB  - The purpose of this study is to understand self-rated health (SRH) trajectories
      by social location (race/ethnicity by gender by social class) among married
      individuals in the United States. We estimate multilevel models of SRH using six
      observations from 1980 to 2000 from a nationally representative panel of married
      individuals initially aged 25-55 (Marital Instability Over the Life Course
      Study). Results indicate that gender, race/ethnicity, and social class are
      associated with initial SRH disparities. Women are less healthy than men; people
      of color are less healthy than whites; lower educated individuals are less
      healthy than higher educated individuals. Women's health declined slower than
      men's but did not differ by race/ethnicity or education. Results from complex
      intersectional models show that white men with any college had the highest
      initial SRH. Only women with any college had significantly slower declines in SRH
      compared to white men with any college. For married individuals of all ages, most
      initial SRH disparities persist over twenty years. Intersecting statuses show
      that education provides uneven health benefits across racial/ethnic and gender
      subgroups.

PMID- 29593905
TI  - Conceptions of Healthy Aging Held by Relatives of Older Persons in Isan-Thai
      Culture: A Phenomenographic Study.
AB  - In Thailand, family nurses are expected to provide support for older persons and
      their family members to promote healthy aging. Family bonds are strong, and
      relatives are expected to take care of their older family members. However, there
      is limited research on how older persons' family members perceive healthy aging.
      This study aimed to describe the conceptions of healthy aging held by the
      children and grandchildren of older persons in northeast Thailand. In a
      phenomenographic study, 14 interviews were performed to qualitatively analyze
      different conceptions of healthy aging. Four descriptive categories emerged:
      being independent, not being afflicted by diseases or illnesses, being a giver
      and a receiver, and being wise. The conceptions of healthy aging entail both
      autonomy and interdependence. The relative's perspective needs to be considered
      when policies relating to healthy aging are implemented in the community and when
      family nurses provide support to families to promote healthy aging.

PMID- 29593906
TI  - Estimating Long-Term Care Costs among Thai Elderly: A Phichit Province Case
      Study.
AB  - Background: Rural-urban inequality in long-term care (LTC) services has been
      increasing alongside rapid socioeconomic development. This study estimates the
      average spending on LTC services and identifies the factors that influence the
      use and cost of LTC for the elderly living in urban and rural areas of Thailand.
      Methods: The sample comprised 837 elderly aged 60 years drawn from rural and
      urban areas in Phichit Province. Costs were assessed over a 1-month period.
      Direct costs of caregiving and indirect costs (opportunity cost method) were
      analyzed. Binary logistic regression was performed to determine which factors
      affected LTC costs. Results: The total annual LTC spending for rural and urban
      residents was on average USD 7,285 and USD 7,280.6, respectively. Formal care and
      informal care comprise the largest share of payments. There was a significant
      association between rural residents and costs for informal care, day/night care,
      and home renovation. Conclusions: Even though total LTC expenditures do not seem
      to vary significantly across rural and urban areas, the fundamental differences
      between areas need to be recognized. Reorganizing country delivery systems and
      finding a balance between formal and informal care are alternative solutions.

PMID- 29593907
TI  - Effects of a 12-Week Exercise Training Program on Physical Function in
      Institutionalized Frail Elderly.
AB  - With the increase in life expectancy, the Brazilian elderly population has risen
      considerably. However, longevity is usually accompanied by problems such as the
      loss of functional capacity, cognitive decline, frailty syndrome, and
      deterioration in anthropometric parameters, particularly among those living in
      long-term care facilities. This randomized controlled trial aimed to verify the
      effects of exercise training on biochemical, inflammatory, and anthropometric
      indices and functional performance in institutionalized frail elderly. The sample
      consisted of 37 elderly people of both genders, aged 76.1 +/- 7.7 years, who were
      randomly allocated into 2 groups: 13 individuals in the exercise group (EG) and
      24 in the control group (CG). Anthropometrics, clinical history, functional
      tests, and biochemical evaluation were measured before and after the completion
      of a physical exercise program, which lasted for 12 weeks. The 12-week exercise
      program for frail elderly residents in a long-term care facility was efficient in
      improving muscle strength, speed, agility, and biochemical variables, with
      reversal of the frailty condition in a considerable number. However, no effects
      in anthropometric and inflammatory parameters were noted.

PMID- 29593909
TI  - Qualitative Analysis of Primary Fingerprint Pattern in Different Blood Group and
      Gender in Nepalese.
AB  - Dermatoglyphics, the study of epidermal ridges on palm, sole, and digits, is
      considered as most effective and reliable evidence of identification. The
      fingerprints were studied in 300 Nepalese of known blood groups of different ages
      and classified into primary patterns and then analyzed statistically. In both
      sexes, incidence of loops was highest in ABO blood group and Rh +ve blood types,
      followed by whorls and arches, while the incidence of whorls was highest followed
      by loops and arches in Rh -ve blood types. Loops were higher in all blood groups
      except "A -ve" and "B -ve" where whorls were predominant. The fingerprint pattern
      in Rh blood types of blood group "A" was statistically significant while in
      others it was insignificant. In middle and little finger, loops were higher
      whereas in ring finger whorls were higher in all blood groups. Whorls were higher
      in thumb and index finger except in blood group "O" where loops were predominant.
      This study concludes that distribution of primary pattern of fingerprint is not
      related to gender and blood group but is related to individual digits.

PMID- 29593908
TI  - Can Driving-Simulator Training Enhance Visual Attention, Cognition, and Physical
      Functioning in Older Adults?
AB  - Virtual reality offers a good possibility for the implementation of real-life
      tasks in a laboratory-based training or testing scenario. Thus, a computerized
      training in a driving simulator offers an ecological valid training approach.
      Visual attention had an influence on driving performance, so we used the reverse
      approach to test the influence of a driving training on visual attention and
      executive functions. Thirty-seven healthy older participants (mean age: 71.46 +/-
      4.09; gender: 17 men and 20 women) took part in our controlled experimental
      study. We examined transfer effects from a four-week driving training (three
      times per week) on visual attention, executive function, and motor skill. Effects
      were analyzed using an analysis of variance with repeated measurements.
      Therefore, main factors were group and time to show training-related benefits of
      our intervention. Results revealed improvements for the intervention group in
      divided visual attention; however, there were benefits neither in the other
      cognitive domains nor in the additional motor task. Thus, there are no broad
      training-induced transfer effects from such an ecologically valid training
      regime. This lack of findings could be addressed to insufficient training
      intensities or a participant-induced bias following the cancelled randomization
      process.

PMID- 29593910
TI  - Patients' and Health Professionals' Experiences of Using Virtual Reality
      Technology for Upper Limb Training after Stroke: A Qualitative Substudy.
AB  - Background: In recent years, virtual reality (VR) therapy systems for upper limb
      training after stroke have been increasingly used in clinical practice. Therapy
      systems employing VR technology can enhance the intensity of training and can
      also boost patients' motivation by adding a playful element to therapy. However,
      reports on user experiences are still scarce. Methods: A qualitative
      investigation of patients' and therapists' perspectives on VR upper limb
      training. Semistructured face-to-face interviews were conducted with six patients
      in the final week of the VR intervention. Therapists participated in two focus
      group interviews after the completion of the intervention. The interviews were
      analyzed from a phenomenological perspective emphasizing the participants'
      perceptions and interpretations. Results: Five key themes were identified from
      the patients' perspectives: (i) motivational factors, (ii) engagement, (iii)
      perceived improvements, (iv) individualization, and (v) device malfunction. The
      health professionals described the same themes as the patients but less
      positively, emphasizing negative technical challenges. Conclusion: Patients and
      therapists mainly valued the intensive and motivational character of VR training.
      The playful nature of the training appeared to have a significant influence on
      the patients' moods and engagement and seemed to promote a "gung-ho" spirit, so
      they felt that they could perform more repetitions.

PMID- 29593911
TI  - First Report of blaCTX-M-28 in Enterobacteriaceae Isolates in the United Arab
      Emirates.
AB  - Background: The CTX-M family of extended-spectrum beta lactamase (ESBL) enzymes
      is comprised of over 60 blaCTX-M gene variants with the predominance of blaCTX-M
      15 in many regions. In this report, we present the first description of blaCTX-M
      28 in the United Arab Emirates. Methods: Forty-five non-duplicate ESBL producing
      isolates identified in a secondary care facility in the United Arab Emirates from
      June to July 2016 were studied. Gene sequencing was performed and DNA sequences
      were annotated using the BLAST program to identify the gene subtypes. Results:
      The majority of the ESBL positive isolates were E. coli (n/N = 39/45; 86.6%)
      followed by K. pneumoniae (n = 5) and K. oxytoca (n = 1). All isolates harboured
      blaCTX-M and blaTEM genes, 18 had blaSHV, and 2 were blaVIM positive. Thirty
      seven isolates (82.2%) were positive for blaCTX-M-28. Other blaCTX-M genes
      identified include blaCTX-M-167 (n = 2; isolates #1 and 26) and one each for
      blaCTX-M-38, blaCTX-M-163, and blaCTX-M-198. No blaCTX-M-15 was identified. The
      predominant blaTEM subtype was blaTEM-171 (n = 8) followed by one of each of
      blaTEM-120, blaTEM-163, and blaTEM-206. The blaSHV subtypes were blaSHV-148 and
      blaSHV-187. Conclusion: The findings indicate the first description of blaCTX-M
      28 in a setting where blaCTX-M-15 was previously predominant.

PMID- 29593912
TI  - Antimicrobial Susceptibility among Colistin, Sulbactam, and Fosfomycin and a
      Synergism Study of Colistin in Combination with Sulbactam or Fosfomycin against
      Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii.
AB  - This in vitro study aimed to determine the activity of colistin plus sulbactam
      and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB).
      Fifteen clinical isolates were obtained from patients admitted to Phyathai II
      International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The
      antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were
      evaluated using the E-test or broth microdilution and the synergistic activity of
      the antibacterial combinations (colistin plus sulbactam or fosfomycin) was
      determined using the chequerboard method. Clonal relationships were explored
      using repetitive element palindromic- (REP-) PCR. The CRAB isolates were
      categorized by REP-PCR in 8 groups [A-H]. All CRAB isolates were universally
      susceptible to colistin but only 20.0% were susceptible to sulbactam. The MIC
      ranges for colistin, sulbactam, and fosfomycin were 0.75-2 mg/L, 2-96 mg/L, and
      64-256 mg/L, respectively. A chequerboard assay revealed that the rates of
      synergistic and additive effect rates of colistin plus sulbactam and colistin
      plus fosfomycin were 53.3% and 73.3% of isolates, respectively. No antagonistic
      effect in any colistin-based combination was observed. However, almost CRAB
      strains in clone A showed the synergy or additive effects of colistin-sulbactam
      combination, whereas the other clone (B-H) mostly showed indifferent effects. In
      conclusion, colistin plus sulbactam and colistin plus fosfomycin against CRAB
      seem to be interesting option but the efficacy in clinical use has to be
      evaluated.

PMID- 29593913
TI  - The Impact of Pinless Navigation in Conventionally Aligned Total Knee
      Arthroplasty.
AB  - Background: Restoration of the mechanical axis is a main objective in total knee
      replacement (TKR). Aim of this study was to analyse the verification tool of a
      pinless navigation system in conventional TKR (cTKR). Methods: In a prospective
      study, 147 TKR were performed by conventional technique. Using the "pinless
      verification" mode of a smartphone based navigation system, the cutting block
      position and final resection plane for distal femur and proximal tibial resection
      were measured. If necessary, the block position or resection level were
      optimized, corrections were protocolled. Postoperatively, standardized
      radiographs were performed. Results: In 65.3%, intraoperative measurements
      changed the surgical procedure (corrections: 20.4% femoral, 25.9% tibial, 19%
      both). The additional time for surgery compared to cTKR averaged 6 minutes (79 +/
      15 versus 73 +/- 17 minutes). Using navigation data, the final femoral and
      tibial axes were in 93% within a range of +/-2 degrees . A mean difference of 1.4
      degrees  and 1.6 degrees  could be shown between the final measurement of the
      navigation system and the postoperative mLDFA and mMPTA. Conclusion:
      Intraoperative pinless navigation has impact on the surgical procedure in the
      majority of cTKR. It represents a less time-consuming tool to improve implant
      position while maintaining the routine of conventional technique.

PMID- 29593914
TI  - Rituximab Induced Pulmonary Edema Managed with Extracorporeal Life Support.
AB  - Though rare, rituximab has been reported to induce severe pulmonary edema. We
      describe the first report of ECLS utilization for this indication. A 31-year-old
      female with severe thrombotic thrombocytopenic purpura developed florid pulmonary
      edema after rituximab infusion. Despite advanced ventilatory settings, she
      developed severe respiratory acidosis and remained hypoxemic with a significant
      vasopressor requirement. Since her pulmonary insult was likely transient, ECLS
      was considered. Due to combined cardiorespiratory failure, she received support
      with peripheral venoarterial ECLS. During her ECLS course, she received daily
      plasmapheresis and high dose steroids. Her pulmonary function recovered and she
      was decannulated after 8 days. She was discharged after 23 days without residual
      sequelae.

PMID- 29593915
TI  - Surgery to Treat Symptomatic Mobile Cecum Syndrome Is Safe and Associated with
      Good Recovery Outcomes.
AB  - The mobile cecum syndrome includes a spectrum of conditions. The cecal volvulus
      represents the acute form, with typical feature of a bowel obstruction that needs
      immediate operative treatment. On the other hand, a chronic form of mobile cecum
      syndrome which is the most common form reported a history of intermittent crampy
      abdominal pain, distension, and constipation. In this study, five patients came
      to our attention during the last ten years, presenting different symptoms due to
      a mobile cecum. All patients were investigated by several diagnostic techniques
      according to the specific clinical setting. All patients were found to have the
      cecum and ascending colon unattached to the posterior peritoneum. Surgery was the
      treatment of choice. In our experience, the best diagnostic technique was
      computed tomography scan, especially if performed in the Trendelenburg position.
      We also propose virtual colonoscopy as a good option for diagnosis (in patients
      with chronic syndrome) and follow-up after surgery. In conclusion, laparoscopic
      approach guaranteed a good result, with no symptoms of recurrence, in both acute
      and elective treatments. The diagnosis of mobile cecum needs a high index of
      suspicion and a targeted radiological investigation. Surgery, especially
      laparoscopic cecopexy and appendectomy, is the recommended treatment.

PMID- 29593916
TI  - Primary Pancreatic Burkitt's Lymphoma: A Case Report and Review of the
      Literature.
AB  - Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal
      site of Non-Hodgkin's lymphoma (NHL). It represents less than 1% of NHL. Out of
      which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs
      in children and presenting in adults is uncommon. The prevalence of pancreatic
      Burkitt lymphoma is not known as the incidence is significantly low. Clinical
      features of PPL are predominantly nonspecific and can become difficult with
      associated inflammation of pancreas. Differentiation of lymphoma to
      adenocarcinoma is important as chemotherapy is the main stay of treatment in
      lymphoma. We report a case of 68-year-old female who presented with nonspecific
      symptoms and was found to have obstructive jaundice secondary to pancreatic head
      neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare
      presentation.

PMID- 29593917
TI  - A Case of Unresolved and Worsening Retroperitoneal Abscess.
AB  - Retroperitoneal abscess is a rare condition which is difficult to diagnose and
      treat because of its insidious onset. Herein, we present a case of
      retroperitoneal abscess secondary to a perforation that occurred during an ERCP.
      A 54-year-old female patient was admitted to an outside hospital with gallstone
      pancreatitis and underwent ERCP with sphincterotomy followed by laparoscopic
      cholecystectomy. An abdominal CT scan was performed at the outside hospital 10
      days later for worsening abdominal pain which showed multiple loculated pockets
      in the right upper and lower quadrant. Her condition improved after IV
      antibiotics and percutaneous drainage. Her symptoms recurred a month later and
      she presented to our hospital. Repeat abdominal CT scan at our hospital revealed
      recurrence of her abscesses. Multiple drains were placed and the abscess cavity
      was washed out without much improvement. EGD revealed a small mucosal defect in
      the distal portion of the duodenal bulb which was closed successfully using an
      over-the-scope clip. Repeat CT scan after 8 weeks from the endoscopic closure
      showed near complete resolution of the abscess. ERCP-associated perforation is a
      rare complication and can be challenging to diagnose and treat; prompt
      recognition is mandatory for favorable prognosis. Our patient was managed
      successfully via nonsurgical approach.

PMID- 29593918
TI  - A Case of Polymicrobial Bacteremia in a Patient Undergoing Chemotherapy.
AB  - We report an aggressive case of polymicrobial bacteremia in a patient with renal
      pelvis carcinoma. A 76-year-old man developed watery diarrhea after undergoing
      chemotherapy. He became unconscious and went into shock. Laboratory data showed
      severe neutropenia, renal failure, and lactic acidosis. Chest radiography showed
      multiple opacities. He died despite aggressive fluid resuscitation, catecholamine
      administration, antibiotic treatment, and mechanical ventilation. Blood culture
      isolates included Escherichia coli, Klebsiella pneumoniae, Streptococcus
      pneumoniae, Acinetobacter baumannii, and Moraxella catarrhalis. The foci of
      bacteremia were the respiratory tract and the bowel. The two infection foci and
      polymicrobial bacteremia are thought to be associated with the patient's poor
      prognosis. Although polymicrobial bacteremia is rare, awareness of this condition
      and of the rare causative pathogens, such as A. baumannii and M. catarrhalis,
      especially in patients with comorbidities and immunosuppression will help treat
      the patients with bacteremia.

PMID- 29593919
TI  - Double Native Valve Infective Endocarditis due to Capnocytophaga canimorsus:
      First Reported Case Caused by a Lion Bite.
AB  - Capnocytophaga canimorsus is a Gram-negative bacilli that is part of the normal
      oral flora of dogs and some cats; it is well known to cause septicemia and
      endocarditis after their bite. This is the first reported case of infective
      endocarditis affecting both native mitral and aortic valves after a lion bite in
      a patient with heavy ethanol consumption, who ultimately died after valve
      replacements.

PMID- 29593920
TI  - A Case Report of Peritoneal Tuberculosis: A Challenging Diagnosis.
AB  - Peritoneal tuberculosis is a disease which can mimick malignancy especially in
      women who present with ascites and elevated CA125 levels. It should always be
      considered in differential diagnosis, but the diagnosis is rarely easy for
      clinicians. A young female patient who presented with abdomen tenderness and
      diagnosed with peritoneal tuberculosis as a result of performed tests is
      discussed hereby in the case report. We expect that this case report adds to the
      existing literature on this subject.

PMID- 29593921
TI  - Unilateral Asterixis in Arm and Leg Caused by Internal Capsula Stroke.
AB  - We report an unusual clinical manifestation of ischemic stroke with acute right
      sided asterixis affecting the arm as well as the leg due to a lesion in the left
      posterior limb of the internal capsula. After treatment with intravenous
      thrombolysis the patient made a good recovery. Notably, in this case unilateral
      asterixis affected the arm as well as the leg, resulting in postural and gait
      instability. In addition, damage in the basal ganglia-thalamo-cortical network,
      as in our patient, has to be distinguished from other supratentorial causes of
      acute asterixis like thalamic or frontal lobe lesions linked to the cerebello
      brainstem-thalamo-frontal lobe circuits.

PMID- 29593922
TI  - Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer
      Syndrome.
AB  - The treatment of cancer is a rapidly evolving field. As more chemotherapeutic
      agents become available, reporting the side effects of these agents in clinical
      practice becomes increasingly important. Nivolumab is one of the chemotherapeutic
      agents commonly used for treatment of renal cell carcinoma, metastatic melanoma,
      and metastatic non-small cell lung cancer. While common side effects are known
      and well documented, encephalitis is documented as an extremely rare side effect.
      We present the case of an extremely rare side effect to a common chemotherapeutic
      agent.

PMID- 29593923
TI  - Delayed Adjacent Level Spondylodiscitis after Initial Surgery with Instrumented
      Spinal Fusion: A Report of Three Cases and Review of the Literature.
AB  - To date, 2 cases of adjacent level spondylodiscitis occurring a few months after
      initial spinal fusion were reported. However, the development of delayed adjacent
      level spondylodiscitis is very rare. The authors report 3 cases of
      spondylodiscitis that occurred at the proximal adjacent level of the fused spine
      more than 1 year after the initial surgery. Antibiotic treatment was initially
      chosen in all three cases. In two of the cases, progressive neurological deficit
      occurred at the level of the infection due to compression of neural elements and
      spinal instability. For these patients, additional spinal fusion was performed.
      In each of the three cases, the selected treatment resulted in successful bony
      fusion at the level of the spondylodiscitis. According to the National Nosocomial
      Infections Surveillance System, deep wound infection is defined as occurring
      within 1 year after surgery with instrumentation. The spondylodiscitis in the
      present cases occurred more than 1 year after the initial surgery, suggesting
      that these cases may be considered as adjacent segment disease rather than
      surgical site infection.

PMID- 29593924
TI  - Subacute Urinary Retention due to a Subpubic Cartilaginous Cyst Treated with
      Surgical Resection and Internal Fixation: A Case Report and Review of the
      Literature.
AB  - A subpubic cartilaginous cyst is a rare mass lesion derived from the pubic
      symphysis, which can cause acute or subacute urinary retention. We report a case
      of a subpubic cartilaginous cyst in a 62-year-old woman that caused lower
      abdominal pain and subacute urinary retention, requiring surgical resection. On
      physical examination, a hard, flexible, nontender mass, 4 cm in diameter, was
      palpable along the lower border of the pubic bone, extending to the perineum.
      Magnetic resonance imaging revealed a clearly distinct (3.8 cm * 3.8 cm * 7.2 cm)
      mass on the midpelvic side of the pelvis, centered on the pubic joint. We
      proceeded with en bloc resection of the mass, including a resection margin of 1
      cm on either side. The bony defect was fixed with a locking plate. On
      pathological assessment, the mass was diagnosed as a subpubic cartilaginous cyst
      arising from the cartilage of the pubic symphysis. No tumor recurrence was
      identified over a 4-year follow-up. Based on our experience, we propose that en
      bloc resection of the mass, including a wider resection centered on the pubic
      symphysis, with internal fixation, is a possible treatment for a subpubic
      cartilaginous cystic mass lesion.

PMID- 29593925
TI  - Hybrid Assistive Limb Intervention in a Patient with Late Neurological
      Deterioration after Thoracic Myelopathy Surgery due to Ossification of the
      Ligamentum Flavum.
AB  - Purpose: We evaluated improvements in gait after using the Hybrid Assistive Limb
      (HAL(r)) exoskeleton robot in a patient with late-onset neurological
      deterioration of lower extremity function after undergoing thoracic spine surgery
      for a myelopathy due to ossification of the ligamentum flavum. Case Presentation:
      A 70-year-old man participated in ten 20 min sessions of HAL intervention, twice
      weekly for five weeks. The effects of each HAL session were evaluated based on
      changes in performance on the 10 m walk test (10 MWT), lower limb kinematics
      quantified from motion capture, and the activation ratio of the gastrocnemius,
      measured before and after the intervention. Muscle activity was recorded using
      surface electromyography and synchronized to measured kinematics. The HAL
      intervention improved gait speed and step length, with an increase in the hip
      flexion angle during the swing phase and a decrease in the activation ratio of
      the gastrocnemius. The modified Ashworth scale improved from 1+ to 1 and
      International Standards for Neurological and Functional Classification of Spinal
      Cord Injury motor scores from 34 to 49. Conclusion: Intervention using the HAL
      exoskeleton robot may be an effective method to improve functional ambulation in
      patients with chronic spinal disorders.

PMID- 29593926
TI  - Chronological Progression of an Enlarged Styloid Process: A Case Report of Eagle
      Syndrome.
AB  - Eagle syndrome is characterized by an elongated styloid process. However, the
      time frame over which the styloid process becomes elongated and extends is
      unknown. How the condition worsens over time is also unclear. To date, there has
      been no report describing the chronologic change that occurs in the styloid
      process in Eagle syndrome. We describe a 53-year-old patient with Eagle syndrome
      in whom the styloid process enlarged progressively over time and the elongated
      styloid process fused with the hyoid bone. The styloid process was resected via a
      transcervical approach, and the patient's subjective symptoms improved. This is
      the first report showing how the styloid process can enlarge over a few years in
      a patient with Eagle syndrome. Surgical resection via a transcervical approach is
      an appropriate treatment for a patient in whom the styloid process has become
      excessively enlarged and elongated.

PMID- 29593927
TI  - A Case of Rare Complication of Inguinal Parietoplasty according to Lichtenstein:
      Entero Cutaneous Fistula.
AB  - Lichtenstein intervention is currently the classic model of the regulated
      treatment of inguinal hernias by direct local approach. This "tension-free"
      technique satisfies both patients and practitioners. However, it does not often
      evade severe complications of parietal surgery. The authors report their
      treatment experience in rural Africa of a late enterocutaneous fistula which
      aggravated an inguinal hernia repair according to the Lichtenstein procedure.
      Physiopathology, diagnosis, and treatment of that disease are analyzed in the
      light of literature.

PMID- 29593928
TI  - Extra-Anatomic Jump Graft from the Right Colic Vein: A Novel Technique to Manage
      Portal Vein Thrombosis in Liver Transplantation.
AB  - Background: In the context of cirrhosis, portal vein thrombosis (PVT) is present
      in 2.1% to 26% of patients. PVT is no longer considered an absolute
      contraindication for liver transplantation, and nowadays, surgical strategies
      depend on the extent of PVT. Complete PVT is associated with higher morbidity
      rates and poor prognosis, while comparable long-term outcomes can be achieved as
      long as physiological portal inflow is restored. Materials and Methods: We report
      our experience with a 45-year-old patient undergoing liver transplant with a PVT
      (stage III-b). To restore portal vein inflow to the liver, an extra-anatomic jump
      graft from the right colic vein with donor iliac vein interposition was
      constructed. Results: The patient recovered well, with a progressive improvement
      of the general conditions, and was finally discharged on p.o.d. 14. No
      anastomotic defects were found at the postoperative CT scan 10 months after the
      surgery. Conclusion: Our technical innovation represents a valid and safe
      alternative to the cavoportal hemitransposition, providing a proper flow
      restoration and reproducing a physiological setting, while avoiding the
      complications related to the cavoportal shunt. We believe that the reconstitution
      of liver portal inflow should be obtained with the most physiological approach
      possible and considering long-term liver function.

PMID- 29593929
TI  - Colorectal Cancer Presenting as Single Pulmonary Hilar Lymph Node Metastasis.
AB  - Colorectal carcinoma is the second biggest cancer responsible for mortality. Lung
      metastasis is the commonest, following the liver. It is not uncommon to perform
      pulmonary metastasectomy and identify mediastinal metastasis. Previous studies
      have identified incidental lymph node involvement following routine mediastinal
      lymph node clearance in 20-50% of cases. However, solitary intrathoracic lymph
      node metastasis is exceedingly rare. Even when present, it is usually
      metachronous. In our case, we present an exceedingly rare case whereby the
      intrathoracic lymph node metastasis is solitary, not accompanying pulmonary
      disease and with no liver metastasis. We also review the evidence for mediastinal
      lymphadenectomy in the literature.

PMID- 29593930
TI  - Mucinous Carcinomatosis: A Rare Association between an Ovarian Tumor and an E
      GIST.
AB  - Pseudomyxoma peritonei (PMP) and extragastrointestinal stromal tumors (E-GISTs)
      are both rare entities. Most of the time, PMP is associated with an appendiceal
      tumor. An ovarian mucinous tumor can mimic appendiceal metastases. E-GIST is a
      mesenchymal tumor that can arise from the omentum, retroperitoneum, mesentery, or
      pleura. We present a case of an 87-year-old woman with mucinous carcinomatosis
      and acute intestinal occlusion submitted to an emergency laparotomy. She has
      found to have a borderline mucinous tumor of the ovary from the intestinal type
      with several lesions of pseudomyxoma peritonei and an E-GIST from the epiploons
      retrocavity (intermediated risk). In the literature, no relation was found
      between these two rare tumors. E-GIST was an incidental finding in the context of
      a mucinous carcinomatosis.

PMID- 29593931
TI  - A Case of Fibrous Pseudotumor in the Scrotum: Challenge for Diagnosis and
      Testicular Preservation.
AB  - A paratesticular fibrous pseudotumor is a relatively rare benign disease.
      Preoperatively diagnosing a fibrous pseudotumor is challenging because
      distinguishing these masses from malignant tumors on the basis of clinical and
      radiological findings can be difficult. We present a case of a 28-year-old man
      who presented with a painless palpable mass in the right scrotum; the fibrous
      pseudotumor of the tunica vaginalis was treated with organ-sparing surgery.
      Computed tomography and magnetic resonance imaging revealed paratesticular
      tumors. Testicular tumor marker levels were within normal limits. We scheduled
      the patient to undergo tumor biopsy combined with intraoperative rapid diagnosis.
      Frozen section assessment suggested a fibrous pseudotumor without malignancy. We
      successfully performed organ-sparing surgery. Testicular-sparing surgery combined
      with frozen section assessment is primarily used for treating paratesticular
      fibrous pseudotumors.

PMID- 29593932
TI  - Masculinity and Bystander Attitudes: Moderating Effects of Masculine Gender Role
      Stress.
AB  - Objective: The purpose of the current study was to examine the bystander decision
      making process as a mechanism by which men's adherence to various dimensions of
      traditional masculinity is associated with their confidence to intervene in
      sexually aggressive events. Further, this study examined the stress men
      experience from their attempts to adhere to traditional male gender roles as a
      moderator of this mediational path. Method: Participants (n = 252) completed
      measures of traditional masculinity, decisional balance (i.e., weighing the pros
      and cons) for intervening, masculine gender roles stress, and bystander efficacy.
      Results: The belief that men must attain social status was associated with more
      confidence in men's ability to intervene. This effect was mediated by greater
      perceived positive consequences for intervention among men high, but not low, in
      masculine gender role stress. The belief that men should be tough and aggressive
      was associated with greater perceived negative consequences for intervention and
      less confidence to intervene. The belief that men should not act in
      stereotypically feminine ways was directly associated with less confidence for
      intervention. Conclusions: Findings highlight the importance of examining
      masculinity from a multidimensional perspective to better understand how
      adherence to various norms differentially influences bystander behavior. These
      findings may help to inform bystander intervention programming.

PMID- 29593933
TI  - Comparing men who have sex with men and transgender women who use Grindr, other
      similar social and sexual networking apps, or no social and sexual networking
      apps: Implications for recruitment and health promotion.
AB  - Objective: Researchers and public health professionals have increased their
      attention to GPS-based social and sexual networking applications (apps) tailored
      to gay, bisexual, other men who have sex with men (MSM) and transgender women.
      These populations continue to be disproportionately affected by HIV in the United
      States, therefore these apps, in particular Grindr, have become an important
      sampling venue for the recruitment of HIV-related research participants. As such,
      it is essential to identify differences among app users to avoid potential
      sampling bias. This paper seeks to identify differences in MSM and transgender
      women who use Grindr and those who use other similar apps. Methods: A community
      based participatory research (CBPR) approach was used to recruit participants
      online who then completed a 25-item anonymous survey. Five domains were assessed:
      sociodemographics, HIV testing, sexual risk, substance abuse, and use of GPS
      based social and sexual networking apps. Results: 457 participants completed
      surveys. There were significant differences in the sociodemographic
      characteristics by app use, including age, race/ethnicity, sexual orientation,
      and outness. After adjusting for the sociodemographic characteristics associated
      with app use, there were significant differences in HIV risk and substance use
      between the groups. Conclusion: This paper is the first to report on findings
      that compare MSM and transgender women who report using Grindr to MSM and
      transgender women who report using other similar apps. GPS-based social and
      sexual networking apps may offer a valuable recruitment tool for future HIV
      research seeking to recruit populations at increased risk for HIV or those living
      with HIV for therapeutic trials. Because of the differences identified across
      users of different apps, these findings suggest that if researchers recruited
      participants from just one app, they could end up with a sample quite different
      than if they had recruited MSM and transgender women from other apps.

PMID- 29593934
TI  - Semiparametric Mixed Models for Medical Monitoring Data: An Overview.
AB  - The potential to characterize nonlinear progression over time is now possible in
      many health conditions due to advancements in medical monitoring and more
      frequent data collection. It is often of interest to investigate differences
      between experimental groups in a study or identify the onset of rapid changes in
      the response of interest using medical monitoring data; however, analytic
      challenges emerge. We review semiparametric mixed-modeling extensions that
      accommodate medical monitoring data. Throughout the review, we illustrate these
      extensions to the semiparametric mixed-model framework with an application to
      prospective clinical data obtained from 24-hour ambulatory blood pressure
      monitoring, where it is of interest to compare blood pressure patterns from
      children with obstructive sleep apnea to those arising from healthy controls.

PMID- 29593935
TI  - Diagnosis and Clinical Management of Human Papilloma Virus-Related Gingival
      Squamous Cell Carcinoma in a Patient With Leukemia: A Case Report.
AB  - Introduction: Close clinical inspection for intraoral lesions in patients with
      leukemia that develop chronic graft-versus-host disease (cGVHD) is critical.
      Additionally, neoplasias developing in bone marrow transplant patients after
      treatment for leukemia represent a significant obstacle for long-term patient
      survival, necessitating lifetime follow-up by health care providers. This case
      report describes the identification, diagnosis, and treatment of gingival
      squamous cell carcinoma (SCC) in a patient with leukemia who was treated
      previously with a stem cell transplant and referred for routine periodontal care.
      Case Presentation: A 53-year-old male was referred to the Department of
      Periodontics for an assessment of tooth #10 with 2+ mobility and associated cross
      bite occlusion. The patient was diagnosed with acute myeloid leukemia at age 39
      years, received hematopoietic stem cell transplantation (HSCT), and later
      developed cGVHD followed by human papilloma virus (HPV) infections. During the
      periodontal evaluation, a large, non-painful, exophytic, alveolar gingival mass
      was identified and later diagnosed as SCC. It is unusual that oral SCC presents
      as an exophytic, gingival swelling. The patient received comprehensive
      periodontal management in coordination with his otolaryngology team before and
      during the diagnosis of SCC secondary to cGVHD and HPV infection. Conclusions:
      Patients with a history of HSCT treatment for leukemia and subsequent cGVHD are
      at a high risk of developing second primary oral malignancies, including SCC.
      Exposure to oncogenic HPV infection may compound this risk. Therefore, it is
      important for dentists to be aware of special treatment concerns and to
      frequently screen these patients to achieve early diagnosis and treatment of
      these neoplasms.

PMID- 29593936
TI  - Oral Effects and Early Implant Survival Results After Imatinib Discontinuation
      Therapy for Chronic Myelogenous Leukemia: A Case Report.
AB  - Introduction: Little is known regarding the success, failure, or complication
      rates of advanced implant procedures in patients after discontinuation therapy of
      long-term medications for the treatment of chronic myelogenous leukemia (CML).
      This case report presents initial results of a case involving implant placement
      in the mandible and maxilla as well as reduction of palatal oral pigmentation in
      a patient discontinuing long-term tyrosine kinase inhibitor (TKI) therapy for
      CML. Case Presentation: A 57-year-old male was referred to the Department of
      Periodontics, University of Washington, Seattle, Washington, for an assessment of
      edentulous areas (tooth sites #3 and #14) and failing tooth #19. Previous medical
      treatment included oral administration (>10 years) of TKI for the treatment of
      CML. Systemic complications arising from long-term TKI therapy were treated with
      discontinuation of this medication. Concurrently, after multispecialty dental and
      medical consultation, extraction of tooth #19 with immediate implant placement
      and bilateral sinus augmentation with simultaneous implant placement were
      successfully performed during three separate surgical appointments. Additionally,
      marked reduction of oral palatal pigmentation was observed during the surgical
      and restorative phases after TKI discontinuation. Conclusions: Patients with a
      history of long-term TKIs for CML are at risk for developing complications that
      result in discontinuation of therapy. Long-term benefits of therapy may allow
      these patients to enjoy remission with an extended and improved quality of life.
      Patients undergoing discontinuation therapy may seek dental care. Therefore,
      dental providers need to understand these systemic interactions and, with
      multispecialty consultation, may help effectively treat these individuals.

PMID- 29593937
TI  - 2017 Reviewer Acknowledgment.

PMID- 29593938
TI  - Oropharynx HPV status and its relation to HIV infection.
AB  - Background: The number of oropharyngeal lesions caused by HPV (Human
      papillomavirus) has been increasing worldwide in the past years. In spite of the
      clinical relevance of HPV infection in the anogenital tract of HIV-positive
      patients, the relevance of oropharynx HPV infection in these patients is not
      clear. The aim of the present study was to detect HPV infection, and clinical and
      cytological changes in the oropharynx of HIV-positive patients. Methods: Samples
      collected from the oropharynx of 100 HIV-positive patients were subjected to
      hybrid capture (HC), conventional and liquid-based cytology. Clinical data were
      also collected to investigate the relation with HPV status. Results: High and low
      risk types of HPV were present in 8% and 16.7% of the total sample. The mean +/-
      sd (maximum-minimum) of the relative ratio light unit (RLU)/cutoff (CO) was 2.94
      +/- 2.58 (1.09-7.87) and 1.61 +/- 0.65 (1.07-2.8) for high- and low-risk-HPV,
      respectively. By cytology, dysplasia was not detected, but atypical squamous
      cells of undetermined significance (ASC-US) were diagnosed in two samples. No
      clinical change, suggestive of dysplasia/cancer, was detected. Conclusion: Our
      study was able to detect and characterize HPV infection by hybrid capture, which
      may represent a good tool for screening and follow-up of HPV in the studied
      population. The frequency and viral load of HPV were low. Neither clinical nor
      cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx
      of HIV-positive patients.

PMID- 29593939
TI  - Quantitative trait loci associated with soft wheat quality in a cross of good by
      moderate quality parents.
AB  - Information on the genetic control of the quality traits of soft wheat (Triticum
      aestivum) is essential for breeding. Our objective was to identify QTL associated
      with end-use quality. We developed 150 F4-derived lines from a cross of Pioneer
      26R46 * SS550 and tested them in four environments. We measured flour yield (FY),
      softness equivalent (SE), test weight (TW), flour protein content (FP), alkaline
      water retention capacity (AWRC), and solvent retention capacity (SRC) of water
      (WA), lactic acid (LA), sucrose (SU), sodium carbonate (SO). Parents differed for
      nine traits, transgressive segregants were noted, and heritability was high (0.67
      to 0.90) for all traits. We detected QTL distributed on eight genomic regions.
      The QTL with the greatest effects were located on chromosome 1A, 1B, and 6B with
      each affecting at least five of ten quality traits. Pioneer 26R46 is one of the
      best quality soft wheats. The large-effect QTL on 1A novel and accounted for much
      of the variation for AWRC (r2 = 0.26), SO (0.26) and SE (0.25), and FY (0.15) and
      may explain why Pioneer 26R46 has such superior quality. All alleles that
      increased a trait came from the parent with the highest trait value. This
      suggests that in any population that marker-assisted selection for these quality
      traits could be conducted by simply selecting for the alleles at key loci from
      the parent with the best phenotype without prior mapping.

PMID- 29593940
TI  - Will the California Current lose its nesting Tufted Puffins?
AB  - Tufted Puffin (Fratercula cirrhata) populations have experienced dramatic
      declines since the mid-19th century along the southern portion of the species
      range, leading citizen groups to petition the United States Fish and Wildlife
      Service (USFWS) to list the species as endangered in the contiguous US. While
      there remains no consensus on the mechanisms driving these trends, population
      decreases in the California Current Large Marine Ecosystem suggest climate
      related factors, and in particular the indirect influence of sea-surface
      temperature on puffin prey. Here, we use three species distribution models (SDMs)
      to evaluate projected shifts in habitat suitable for Tufted Puffin nesting for
      the year 2050 under two future Intergovernmental Panel on Climate Change (IPCC)
      emission scenarios. Ensemble model results indicate warming marine and
      terrestrial temperatures play a key role in the loss of suitable Tufted Puffin
      nesting conditions in the California Current under both business-as-usual (RCP
      8.5) and moderated (RCP 4.5) carbon emission scenarios, and in particular, that
      mean summer sea-surface temperatures greater than 15  degrees C are likely to
      make habitat unsuitable for breeding. Under both emission scenarios, ensemble
      model results suggest that more than 92% of currently suitable nesting habitat in
      the California Current is likely to become unsuitable. Moreover, the models
      suggest a net loss of greater than 21% of suitable nesting sites throughout the
      entire North American range of the Tufted Puffin, regardless of emission
      reduction strategies. These model results highlight continued Tufted Puffin
      declines-particularly among southern breeding colonies-and indicate a significant
      risk of near-term extirpation in the California Current Large Marine Ecosystem.

PMID- 29593942
TI  - The risk of hospitalization for respiratory tract infection (RTI) in children who
      are treated with high-dose IVIG in Kawasaki Disease: a nationwide population
      based matched cohort study.
AB  - Background: Kawasaki disease (KD) is an immune-mediated systemic vasculitis, and
      infection plays an important role in the pathophysiology of KD. The
      susceptibility to infectious disease in patients with KD remains largely unclear.
      This study aimed to investigate the risk of respiratory tract infection (RTI)
      related hospitalizations in children with KD. Methods: Data from the Taiwanese
      National Health Insurance Research Database was analyzed. We excluded patients
      with history of congenital abnormality, allergic diseases, or hospitalization
      history. Children with KD were selected as KD group and age- and sex-matched non
      KD patients were selected as control group with 1:4 ratio. Both cohorts were
      tracked for one year to investigate the incidences of RTI-related
      hospitalizations. Cox regression hazard model was used to adjust for confounding
      factors and calculate the adjusted hazard ratio (aHR). Results: Between January
      1996 and December 2012, 4,973 patients with KD were identified as the KD group
      and 19,683 patients were enrolled as the control group. An obviously reduced risk
      of RTI-related hospitalizations was observed in KD patients (aHR: 0.75, 95% CI
      [0.66-0.85]). The decreased risk persisted through the first six-months follow-up
      period with a peak protection in 3-6 months (aHR: 0.49, 95% CI [0.37-0.64]).
      Conclusions: KD patients had approximately half reduction of risk for RTI-related
      hospitalizations. The protective effects persisted for at least six months.
      Further studies are warranted to elucidate the entire mechanism and investigate
      the influences of intravenous immunoglobulin.

PMID- 29593941
TI  - Dynamics of Zika virus outbreaks: an overview of mathematical modeling
      approaches.
AB  - Background: The Zika virus was first discovered in 1947. It was neglected until a
      major outbreak occurred on Yap Island, Micronesia, in 2007. Teratogenic effects
      resulting in microcephaly in newborn infants is the greatest public health
      threat. In 2016, the Zika virus epidemic was declared as a Public Health
      Emergency of International Concern (PHEIC). Consequently, mathematical models
      were constructed to explicitly elucidate related transmission dynamics. Survey
      Methodology: In this review article, two steps of journal article searching were
      performed. First, we attempted to identify mathematical models previously applied
      to the study of vector-borne diseases using the search terms "dynamics,"
      "mathematical model," "modeling," and "vector-borne" together with the names of
      vector-borne diseases including chikungunya, dengue, malaria, West Nile, and
      Zika. Then the identified types of model were further investigated. Second, we
      narrowed down our survey to focus on only Zika virus research. The terms we
      searched for were "compartmental," "spatial," "metapopulation," "network,"
      "individual-based," "agent-based" AND "Zika." All relevant studies were included
      regardless of the year of publication. We have collected research articles that
      were published before August 2017 based on our search criteria. In this
      publication survey, we explored the Google Scholar and PubMed databases. Results:
      We found five basic model architectures previously applied to vector-borne virus
      studies, particularly in Zika virus simulations. These include compartmental,
      spatial, metapopulation, network, and individual-based models. We found that Zika
      models carried out for early epidemics were mostly fit into compartmental
      structures and were less complicated compared to the more recent ones. Simple
      models are still commonly used for the timely assessment of epidemics.
      Nevertheless, due to the availability of large-scale real-world data and
      computational power, recently there has been growing interest in more complex
      modeling frameworks. Discussion: Mathematical models are employed to explore and
      predict how an infectious disease spreads in the real world, evaluate the disease
      importation risk, and assess the effectiveness of intervention strategies. As the
      trends in modeling of infectious diseases have been shifting towards data-driven
      approaches, simple and complex models should be exploited differently. Simple
      models can be produced in a timely fashion to provide an estimation of the
      possible impacts. In contrast, complex models integrating real-world data require
      more time to develop but are far more realistic. The preparation of complicated
      modeling frameworks prior to the outbreaks is recommended, including the case of
      future Zika epidemic preparation.

PMID- 29593943
TI  - Tumor immunity landscape in non-small cell lung cancer.
AB  - Even with the great advances in immunotherapy in recent years, the response rate
      to immune checkpoint inhibitor therapy for non-small cell lung cancer is only
      about 20%. We aimed to identify new features that would better predict which
      patients can benefit from an immune checkpoint blocker. This study is based on
      the publicly available gene expression data from The Cancer Genome Atlas lung
      cancer samples and the newly released mutation annotation data. We performed a
      comprehensive analysis by correlating patient cytolytic activity index,
      mutational signatures, and other immune characteristics in four stratified
      patient groups. The results cytolytic activity index are highly correlated with
      immune infiltration scores, T cell infiltration scores and TCR clonality scores
      in lung cancer. In addition, we observed that the mutational event signatures
      might play a more important role in predicting immunotherapy response in squamous
      cell carcinoma and two subgroups of adenocarcinomas. Our analysis illustrates the
      utility of integrating both tumor immune and genomic landscape for a better
      understanding of immune response in lung cancer.

PMID- 29593944
TI  - The first Oligocene sea turtle (Pan-Cheloniidae) record of South America.
AB  - The evolution and occurrence of fossil sea turtles at the Pacific margin of South
      America is poorly known and restricted to Neogene (Miocene/Pliocene) findings
      from the Pisco Formation, Peru. Here we report and describe the first record of
      Oligocene (late Oligocene, ~24 Ma) Pan-Cheloniidae sea turtle remains of South
      America. The fossil material corresponds to a single, isolated and well-preserved
      costal bone found at the Montanita/Olon locality, Santa Elena Province, Ecuador.
      Comparisons with other Oligocene and extant representatives allow us to confirm
      that belongs to a sea turtle characterized by: lack of lateral ossification,
      allowing the dorsal exposure of the distal end of ribs; dorsal surface of bone
      sculptured, changing from dense vermiculation at the vertebral scute region to
      anastomosing pattern of grooves at the most lateral portion of the costal. This
      fossil finding shows the high potential that the Ecuadorian Oligocene outcrops
      have in order to explore the evolution and paleobiogeography distribution of sea
      turtles by the time that the Pacific and the Atlantic oceans were connected via
      the Panama basin.

PMID- 29593945
TI  - Postoperative Seizure Rate After Transcortical Resection of Subcortical Brain
      Tumors and Colloid Cysts: A Single Surgeon's Experience.
AB  - When deciding on a surgical route to reach subcortical brain tumors and colloid
      cysts, many surgeons advocate the use of transcallosal, transsulcal, or skull
      base approaches over transcortical approaches due to a high reported incidence of
      postoperative seizures. We have retrospectively analyzed all patients operated
      upon by a senior neurosurgeon (Ricardo J. Komotar) who undertook transcortical
      approaches for the resection of subcortical brain tumors and colloid cysts. We
      have also performed a comprehensive review of the literature to estimate
      postoperative seizure risk after transcortical approaches for the resection of
      deep tumors and colloid cysts. Of 27 patients who underwent transcortical
      approaches for the resection of subcortical brain tumors and colloid cysts, zero
      had postoperative seizures. A comprehensive review of the literature shows an
      8.3% postoperative risk of seizures after the transcortical approach. Our
      institution has never experienced a postoperative seizure following the
      transcortical approach for the resection of deep tumors and colloid cysts. For
      this reason, we advocate selecting a surgical approach that obtains adequate
      lesion exposure and minimizes the violation and retraction of eloquent cortex,
      venous structures, and white matter tracts, rather than on presumed postoperative
      seizure risk.

PMID- 29593946
TI  - Prevalence of Type 2 Diabetes Mellitus Among Urban Bihari Communities in Dhaka,
      Bangladesh: A Cross-sectional Study in a Minor Ethnic Group.
AB  - Introduction The prevalence, disease progression, and treatment outcomes for
      patients with type 2 diabetes vary significantly between ethnic groups. The
      Bihari community constitutes one of the most vulnerable populations in Bangladesh
      on the basis of access to health services and other fundamental rights. Our study
      aimed at finding out the prevalence and risk factors of type 2 diabetes among the
      Bihari adults in Dhaka city. Methods This cross-sectional community-based study
      was carried out among stranded Pakistanis (known as Bihari) living in camps in
      the Mirpur area from July 2014 to June 2015. Laboratory-based oral glucose
      tolerance test (OGTT) was the basis for the diagnosis of type 2 diabetes mellitus
      (DM). Anthropometric measurements, blood pressure, biochemical tests, family
      history, and socioeconomic information were obtained to determine the risk
      factors. Results The prevalence of diabetes mellitus (DM), impaired glucose
      tolerance (IGT), and impaired fasting glucose (IFG) were estimated at 10.11%,
      8.74%, and 4.55%, respectively. Increased diastolic blood pressure, serum
      triglyceride, and cholesterol level were observed to be significantly (p < 0.05)
      associated with diabetes. Also, the presence of diabetes, high blood pressure,
      and obesity among relatives significantly increased the probability of diabetes.
      Conclusions To the best of our knowledge, this is the first study on diabetes
      prevalence among the Bihari community in Bangladesh. The prevalence of type 2
      diabetes mellitus was found to be higher among the Bihari community compared to
      the general population in Bangladesh. Health planners and policymakers should
      realize the alarming situation and identified risk factors and consider the minor
      ethnic groups during decision-making regarding prevention and control of diabetes
      and other noncommunicable diseases.

PMID- 29593947
TI  - Angioplasty is an Effective Treatment for Vasospasm Following Pituitary Apoplexy
      and Tumor Resection.
AB  - Pituitary apoplexy is a clinical syndrome characterized by acute headache, visual
      changes, and decreased consciousness occurring in association with hemorrhage or
      infarct of an existing pituitary adenoma. Surgical management involves tumor
      resection and decompression of surrounding structures including the optic
      apparatus. Vasospasm is a rare but potentially devastating complication of
      pituitary apoplexy. We present a case of pituitary apoplexy in a 28-year-old male
      treated with emergent endoscopic transsphenoidal resection. On postoperative day
      seven, following  surgical resection, the patient developed neurologic deficits
      and motor weakness, and severe vasospasm was diagnosed. This is a novel case of
      intra-arterial verapamil and angioplasty used to treat vasospasm following
      surgical decompression for pituitary apoplexy. The patient experienced complete
      recovery of motor deficits following treatment. The authors propose angioplasty
      as an effective treatment for postoperative vasospasm following transphenoidal
      surgery for pituitary apoplexy in the presence of focal vessel stenosis.

PMID- 29593948
TI  - Isolating the roles of different forcing agents in global stratospheric
      temperature changes using model integrations with incrementally added single
      forcings.
AB  - Satellite instruments show a cooling of global stratospheric temperatures over
      the whole data record (1979-2014). This cooling is not linear, and includes two
      descending steps in the early 1980s and mid-1990s. The 1979-1995 period is
      characterized by increasing concentrations of ozone depleting substances (ODS)
      and by the two major volcanic eruptions of El Chichon (1982) and Mount Pinatubo
      (1991). The 1995-present period is characterized by decreasing ODS concentrations
      and by the absence of major volcanic eruptions. Greenhouse gas (GHG)
      concentrations increase over the whole time period. In order to isolate the roles
      of different forcing agents in the global stratospheric temperature changes, we
      performed a set of AMIP-style simulations using the NASA Goddard Earth Observing
      System Chemistry-Climate Model (GEOSCCM). We find that in our model simulations
      the cooling of the stratosphere from 1979 to present is mostly driven by changes
      in GHG concentrations in the middle and upper stratosphere and by GHG and ODS
      changes in the lower stratosphere. While the cooling trend caused by increasing
      GHGs is roughly constant over the satellite era, changing ODS concentrations
      cause a significant stratospheric cooling only up to the mid-1990s, when they
      start to decrease because of the implementation of the Montreal Protocol.
      Sporadic volcanic events and the solar cycle have a distinct signature in the
      time series of stratospheric temperature anomalies but do not play a
      statistically significant role in the long-term trends from 1979 to 2014. Several
      factors combine to produce the step-like behavior in the stratospheric
      temperatures: in the lower stratosphere, the flattening starting in the mid
      1990's is due to the decrease in ozone depleting substances; Mount Pinatubo and
      the solar cycle cause the abrupt steps through the aerosol-associated warming and
      the volcanically induced ozone depletion. In the middle and upper stratosphere,
      changes in solar irradiance are largely responsible for the step-like behavior of
      global temperatures anomalies, together with volcanically induced ozone depletion
      and water vapor increases in the post-Pinatubo years.

PMID- 29593949
TI  - A Vesicular Stomatitis Virus-Inspired DNA Nanocomplex for Ovarian Cancer Therapy.
AB  - Gene therapy provides a novel method for cancer therapy. This study shows a DNA
      nanocomplex that is inspired from vesicular stomatitis virus (VSV) for ovarian
      cancer therapy. This DNA nanocomplex consists of a cationized monomethoxy poly
      (ethylene glycol)-poly (d,l-lactide) (MPEG-PLA) nanoparticle and a plasmid
      encoding the matrix protein of vesicular stomatitis virus (VSVMP) that plays a
      critical role in the VSV-induced apoptosis of cancer cells. The cationized MPEG
      PLA nanoparticle that is self-assembled by MPEG-PLA copolymer and N -[1-(2,3
      dioleoyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTAP) has low
      cytotoxicity and high transfection efficiency (>80%). Intraperitoneal
      administration of the p VSVMP nanocomplex remarkably inhibits the intraperitoneal
      metastasis of ovarian cancer and does not cause significant systemic toxicity.
      The apoptosis induction and anti-angiogenesis are involved in the anticancer
      mechanism. This work demonstrates a VSV-inspired DNA nanocomplex that has
      potential application for the treatment of intraperitoneal metastasis of ovarian
      cancer.

PMID- 29593950
TI  - Characterization of HIF-1alpha/Glycolysis Hyperactive Cell Population via Small
      Molecule-Based Imaging of Mitochondrial Transporter Activity.
AB  - The characterization of cancer stem-like cells (CSCs) has profound implications
      for elucidating cancer biology and developing treatment strategies. Although
      surface markers are already used to identify CSCs, the expression of these
      markers is controversially linked to the phenotypes in different types of tumors
      and does not represent all functionally relevant of CSCs. Very recently,
      hyperactive HIF-1alpha/glycolysis metabolic pathway is recognized as a master
      regulator of CSCs. In this study, a near-infrared fluorescent small-molecule, IR
      780, is identified for the exclusive characterization of human CSCs through the
      HIF-1alpha/glycolysis dependent mitochondrial transporter ABCB10's activity. The
      results identified for the first time that ABCB10 is involved in the preferential
      uptake of IR-780 in CSCs, which is regulated by HIF-1alpha via the direct
      interaction with the binding site of ABCB10 gene promoter region. In addition, IR
      780 is demonstrated to conjugate with anticancer drug 5-fluorouracil to act as a
      potential drug delivery carrier for CSC-targeted therapy. Thus, the studies
      provide a new rational approach independent of surface markers to characterize
      CSCs via small-molecule-based imaging of HIF-1alpha/glycolysis hyperactive
      metabolic pathway dependent mitochondrial transporter's activity, which holds
      promise for the further development of CSCs targeted diagnostic and therapeutic
      strategies.

PMID- 29593951
TI  - Enhanced Photodynamic Cancer Treatment by Mitochondria-Targeting and Brominated
      Near-Infrared Fluorophores.
AB  - A noninvasive and selective therapy, photodynamic therapy (PDT) is widely
      researched in clinical fields; however, the lower efficiency of PDT can induce
      unexpected side effects. Mitochondria are extensively researched as target sites
      to maximize PDT effects because they play crucial roles in metabolism and can be
      used as cancer markers due to their high transmembrane potential. Here, a
      mitochondria targeting photodynamic therapeutic agent (MitDt) is developed. This
      photosensitizer is synthesized from heptamethine cyanine dyes, which are
      conjugated or modified as follows. The heptamethine meso-position is conjugated
      with a triphenylphosphonium derivative for mitochondrial targeting, the N-alkyl
      side chain is modified for regulation of charge balance and solubility, and the
      indolenine groups are brominated to enhance reactive oxygen species generation
      (ROS) after laser irradiation. The synthesized MitDt increases the cancer uptake
      efficiency due to the lipo-cationic properties of the triphenylphosphonium, and
      the PDT effects of MitDt are amplified after laser irradiation because
      mitochondria are susceptible to ROS, the response to which triggers an apoptotic
      anticancer effect. Consequently, these hypotheses are demonstrated by in vitro
      and in vivo studies, and the results indicate strong potential for use of MitDts
      as efficient single-molecule-based PDT agents for cancer treatment.

PMID- 29593952
TI  - Toroidal Localized Spoof Plasmons on Compact Metadisks.
AB  - Localized spoof surface plasmons (LSSPs) have recently emerged as a new research
      frontier due to their unique properties and increasing applications. Despite the
      importance, most of the current researches only focus on electric/magnetic LSSPs.
      Very recent research has revealed that toroidal LSSPs, LSSPs modes with multipole
      toroidal moments, can be achieved at a point defect in a 2D groove metal array.
      However, this metamaterial shows the limitations of large volume and poor
      compatibility to photonic integrated circuits. To overcome the above challenges,
      here it is proposed and experimentally demonstrated compact planar metadisks
      based on split ring resonators to support the toroidal LSSPs at microwave
      frequencies. Additionally, it is experimentally demonstrated that the toroidal
      LSSPs resonance is very sensitive to the structure changes and the background
      medium. These might facilitate its utilization in the design and application of
      plasmonic deformation sensors and the refractive index sensors.

PMID- 29593953
TI  - Multifunctional Sandwich-Structured Electrolyte for High-Performance Lithium
      Sulfur Batteries.
AB  - Due to its high theoretical energy density (2600 Wh kg-1), low cost, and
      environmental benignity, the lithium-sulfur (Li-S) battery is attracting strong
      interest among the various electrochemical energy storage systems. However, its
      practical application is seriously hampered by the so-called shuttle effect of
      the highly soluble polysulfides. Herein, a novel design of multifunctional
      sandwich-structured polymer electrolyte (polymer/cellulose nonwoven/nanocarbon)
      for high-performance Li-S batteries is demonstrated. It is verified that Li-S
      battery with this sandwich-structured polymer electrolyte delivers excellent
      cycling stability (only 0.039% capacity decay cycle-1 on average exceeding 1500
      cycles at 0.5 C) and rate capability (with a reversible capacity of 594 mA h g-1
      at 4 C). These electrochemical performances are attributed to the synergistic
      effect of each layer in this unique sandwich-structured polymer electrolyte
      including steady lithium stripping/plating, strong polysulfide absorption
      ability, and increased redox reaction sites. More importantly, even with high
      sulfur loading of 4.9 mg cm-2, Li-S battery with this sandwich-structured polymer
      electrolyte can deliver high initial areal capacity of 5.1 mA h cm-2. This
      demonstrated strategy here may open up a new era of designing hierarchical
      structured polymer electrolytes for high-performance Li-S batteries.

PMID- 29593954
TI  - Recent Progress on MOF-Derived Heteroatom-Doped Carbon-Based Electrocatalysts for
      Oxygen Reduction Reaction.
AB  - The oxygen reduction reaction (ORR) is the core reaction of numerous sustainable
      energy-conversion technologies such as fuel cells and metal-air batteries. It is
      crucial to develop a cost-effective, highly active, and durable electrocatalysts
      for ORR to overcome the sluggish kinetics of four electrons pathway. In recent
      years, the carbon-based electrocatalysts derived from metal-organic frameworks
      (MOFs) have attracted tremendous attention and have been shown to exhibit
      superior catalytic activity and excellent intrinsic properties such as large
      surface area, large pore volume, uniform pore distribution, and tunable chemical
      structure. Here in this review, the development of MOF-derived heteroatom-doped
      carbon-based electrocatalysts, including non-metal (such as N, S, B, and P) and
      metal (such as Fe and Co) doped carbon materials, is summarized. It furthermore,
      it is demonstrated that the enhancement of ORR performance is associated with
      favorably well-designed porous structure, large surface area, and high-tensity
      active sites. Finally, the future perspectives of carbon-based electrocatalysts
      for ORR are provided with an emphasis on the development of a clear mechanism of
      MOF-derived non-metal-doped electrocatalysts and certain metal-doped
      electrocatalysts.

PMID- 29593955
TI  - Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation
      and Metabolic Phenotype Alteration.
AB  - Aberrant mitochondrial energy transfer underlies prevalent chronic health
      conditions, including cancer, cardiovascular, and neurodegenerative diseases.
      Mitochondrial transplantation represents an innovative strategy aimed at
      restoring favorable metabolic phenotypes in cells with dysfunctional energy
      metabolism. While promising, significant barriers to in vivo translation of this
      approach abound, including limited cellular uptake and recognition of
      mitochondria as foreign. The objective is to functionalize isolated mitochondria
      with a biocompatible polymer to enhance cellular transplantation and eventual in
      vivo applications. Herein, it is demonstrated that grafting of a polymer
      conjugate composed of dextran with triphenylphosphonium onto isolated
      mitochondria protects the organelles and facilitates cellular internalization
      compared with uncoated mitochondria. Importantly, mitochondrial transplantation
      into cancer and cardiovascular cells has profound effects on respiration,
      mediating a shift toward improved oxidative phosphorylation, and reduced
      glycolysis. These findings represent the first demonstration of polymer
      functionalization of isolated mitochondria, highlighting a viable strategy for
      enabling clinical applications of mitochondrial transplantation.

PMID- 29593956
TI  - Dopant-Free and Carrier-Selective Heterocontacts for Silicon Solar Cells: Recent
      Advances and Perspectives.
AB  - By combining the most successful heterojunctions (HJ) with interdigitated back
      contacts, crystalline silicon (c-Si) solar cells (SCs) have recently demonstrated
      a record efficiency of 26.6%. However, such SCs still introduce
      optical/electrical losses and technological issues due to parasitic
      absorption/Auger recombination inherent to the doped films and the complex
      process of integrating discrete p+- and n+-HJ contacts. These issues have
      motivated the search for alternative new functional materials and simplified
      deposition technologies, whereby carrier-selective contacts (CSCs) can be formed
      directly with c-Si substrates, and thereafter form IBC cells, via a dopant-free
      method. Screening and modifying CSC materials in a wider context is beneficial
      for building dopant-free HJ contacts with better performance, shedding new light
      on the relatively mature Si photovoltaic field. In this review, a significant
      number of achievements in two representative dopant-free hole-selective CSCs,
      i.e., poly(3,4-ethylene dioxythiophene):poly(styrenesulfonate)/Si and transition
      metal oxides/Si, have been systemically presented and surveyed. The focus herein
      is on the latest advances in hole-selective materials modification, interfacial
      passivation, contact resistivity, light-trapping structure and device
      architecture design, etc. By analyzing the structure-property relationships of
      hole-selective materials and assessing their electrical transport properties,
      promising functional materials as well as important design concepts for such CSCs
      toward high-performance SCs have been highlighted.

PMID- 29593957
TI  - Multiplex Photoluminescent Silicon Nanoprobe for Diagnostic Bioimaging and
      Intracellular Analysis.
AB  - Herein, a label-free multiplex photoluminescent silicon nanoprobe (PLSN-probe) is
      introduced as a potential substitute for quantum dots (QDs) in bioimaging. An
      inherently non-photoluminescent silicon substrate is altered to create the PLSN
      probe, to overcome the major drawbacks of presently available QDs. Additionally,
      crystallinity alterations of the multiplane crystalline PLSN-probes lead to broad
      absorption and multiplex fluorescence emissions, which are attributed to the
      simultaneous existence of multiple crystal planes. The PLSN-probe not only
      demonstrates unique optical properties that can be exploited for bioimaging but
      also exhibits cell-selective uptake that allows the differentiation and diagnosis
      of HeLa and fibroblast cells. Moreover, multiplex emissions of the PLSN-probe
      illuminate different organelles such as the nucleus, nucleolemma, and
      cytoskeleton, depending on size-based preferential uptake by the cell organs.
      This in vitro study reveals that cancerous HeLa cells have a higher propensity
      for taking up the PLSN-probe compared to fibroblast cells, allowing the diagnosis
      of cancerous HeLa cells. Additionally, the fluorescence intensity per unit area
      of the cell is found to be a reliable means for distinguishing between dead and
      healthy cells. It is anticipated that the multifunctionality of the PLSN-probes
      will lead to better insight into the use of such probes for bioimaging and
      diagnosis applications.

PMID- 29593958
TI  - 3D-Bioprinted Osteoblast-Laden Nanocomposite Hydrogel Constructs with Induced
      Microenvironments Promote Cell Viability, Differentiation, and Osteogenesis both
      In Vitro and In Vivo.
AB  - An osteoblast-laden nanocomposite hydrogel construct, based on polyethylene
      glycol diacrylate (PEGDA)/laponite XLG nanoclay ([Mg5.34Li0.66Si8O20(OH)4]Na0.66,
      clay)/hyaluronic acid sodium salt (HA) bio-inks, is developed by a two-channel 3D
      bioprinting method. The novel biodegradable bio-ink A, comprised of a
      poly(ethylene glycol) (PEG)-clay nanocomposite crosslinked hydrogel, is used to
      facilitate 3D-bioprinting and enables the efficient delivery of oxygen and
      nutrients to growing cells. HA with encapsulated primary rat osteoblasts (ROBs)
      is applied as bio-ink B with a view to improving cell viability, distribution
      uniformity, and deposition efficiency. The cell-laden PEG-clay constructs not
      only encapsulated osteoblasts with more than 95% viability in the short term but
      also exhibited excellent osteogenic ability in the long term, due to the release
      of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces
      the suitable microenvironment to promote the differentiation of the loaded
      exogenous ROBs, both in vitro and in vivo. This 3D-bioprinting method holds much
      promise for bone tissue regeneration in terms of cell engraftment, survival, and
      ultimately long-term function.

PMID- 29593959
TI  - Photoinduced Rapid Transformation from Au Nanoagglomerates to Drug-Conjugated Au
      Nanovesicles.
AB  - Gold (Au) agglomerates (AGs) are reassembled using Triton X-100 (T) and
      doxorubicin (D) dissolved in ethanol under 185 nm photoirradiation to form TAuD
      nanovesicles (NVs) under ambient gas flow conditions. The positively charged Au
      particles are then electrostatically conjugated with the anionic chains of TD
      components via a flowing drop (FD) reaction. Photoirradiation of the droplets in
      a tubular reactor continues the photophysicochemical reactions, resulting in the
      reassembly of Au AGs and TD into TAuD NVs. The fabricated NVs are
      electrostatically collected onto a polished aluminum rod in a single-pass
      configuration. The dispersion of NVs is employed for bioassays to confirm uptake
      by cells and accumulation in tumors. The chemo-photothermal activity is
      determined both in vitro and in vivo. Different combinations of components are
      also used to fabricate NVs using the FD reaction, and these NVs are suitable for
      gene delivery as well. This newly designed gaseous single-pass process results in
      the reassembly of Au AGs for incorporation with TD without the need of batch wet
      chemical reactions, modifications, separations, or purifications. Thus, this
      process offers an efficient platform for preparing biofunctional Au
      nanostructures that requires neither complex physicochemical steps nor special
      storage techniques.

PMID- 29593960
TI  - Titania-Coated Gold Nano-Bipyramids for Blocking Autophagy Flux and Sensitizing
      Cancer Cells to Proteasome Inhibitor-Induced Death.
AB  - Targeting protein degradation is recognized as a valid approach to cancer
      therapy. The ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway
      are two major pathways for intracellular protein degradation. Proteasome
      inhibitors such as bortezomib are clinically approved for treating malignancies,
      but to date, they are still unsatisfactory for cancer therapy. This study
      identifies titania-coated gold nano-bipyramid (NBP/TiO2) nanostructures as an
      autophagic flux inhibitor, as the smallest NBP/TiO2 nanostructures induce
      significant autophagosome accumulation in human glioblastoma U-87 MG cells via
      blocking the autophagosome-lysosome fusion process and inhibiting lysosomal
      degradation. Further study indicates that NBP/TiO2 nanostructures reduce the
      intracellular level of mature cathepsin B and directly inhibit the proteolytic
      activity of cathepsin B, thereby further inhibiting trypsin-like proteolytic
      activity, which is a potential cotarget for UPS inhibition. NBP/TiO2
      nanostructures interact synergistically with bortezomib to suppress the viability
      of U-87 MG cells, as the combined treatment synergistically induces the
      intracellular accumulation of ubiquitinated protein and endoplasmic reticulum
      stress. In addition, photothermal therapy further synergistically reduces the
      cell viability. In summary, this study suggests that NBP/TiO2 nanostructures
      function as a promising anticancer agent in combination with proteasome
      inhibitors.

PMID- 29593961
TI  - Periodically Self-Pulsating Microcapsule as Programmed Microseparator via ATP
      Regulated Energy Dissipation.
AB  - Living systems can experience time-dependent dynamic self-assembly for periodic,
      adaptive behavior via energy dissipation pathway. Creating in vitro mimics is a
      daunting mission. Here a "living" giant vesicle system that can perform a
      periodic pulsating motion using adenosine-5'-triphosphate (ATP)-fuelled
      dissipative self-assembly is described. This dynamic system is built on transient
      supramolecular interactions between the polymer and cellular energy currency ATP.
      The vesicles capturing ATPs will deviate away from equilibrium, leading to an
      energy ascent that drives a continuous vesicular expansion, until a competitive
      ATP hydrolysis predominates to break the ATP-polymer interactions and deplete the
      energy stored in the vesicles, leading to an opposing vesicular contraction. The
      input of ATP energy can sustain that these vesicles run periodically along this
      reciprocating expansile-contractile process, resembling a "pulsating" behavior.
      ATP level can orchestrate the rhythm, amplitude, and lifetime of this biomimetic
      pulsation. By pre-programming the ATP stimulation protocol, this kind of adaptive
      microcapsules can function as high-performance microseparators to perform size
      selective sieving of different nanoparticles through ATP-mediated transmembrane
      traffic. This man-made system offers a primitive model of time-dependent dynamic
      self-assembly and may offer new ways to build life-like materials with biomimetic
      functions.

PMID- 29593962
TI  - Hierarchically Nanostructured Transition Metal Oxides for Lithium-Ion Batteries.
AB  - Lithium-ion batteries (LIBs) have been widely used in the field of portable
      electric devices because of their high energy density and long cycling life. To
      further improve the performance of LIBs, it is of great importance to develop new
      electrode materials. Various transition metal oxides (TMOs) have been extensively
      investigated as electrode materials for LIBs. According to the reaction
      mechanism, there are mainly two kinds of TMOs, one is based on conversion
      reaction and the other is based on intercalation/deintercalation reaction.
      Recently, hierarchically nanostructured TMOs have become a hot research area in
      the field of LIBs. Hierarchical architecture can provide numerous accessible
      electroactive sites for redox reactions, shorten the diffusion distance of Li-ion
      during the reaction, and accommodate volume expansion during cycling. With rapid
      research progress in this field, a timely account of this advanced technology is
      highly necessary. Here, the research progress on the synthesis methods,
      morphological characteristics, and electrochemical performances of hierarchically
      nanostructured TMOs for LIBs is summarized and discussed. Some relevant prospects
      are also proposed.

PMID- 29593963
TI  - Recent Advances on Functionalized Upconversion Nanoparticles for Detection of
      Small Molecules and Ions in Biosystems.
AB  - Significant progress on upconversion-nanoparticle (UCNP)-based probes is
      witnessed in recent years. Compared with traditional fluorescent probes (e.g.,
      organic dyes, metal complexes, or inorganic quantum dots), UCNPs have many
      advantages such as non-autofluorescence, high chemical stability, large light
      penetration depth, long lifetime, and less damage to samples. This article
      focuses on recent achievements in the usage of lanthanide-doped UCNPs as
      efficient probes for biodetection since 2014. The mechanisms of upconversion as
      well as the luminescence resonance energy transfer process is introduced first,
      followed by a detailed summary on the recent researches of UCNP-based
      biodetections including the detection of inorganic ions, gas molecules, reactive
      oxygen species, and thiols and hydrogen sulfide.

PMID- 29593964
TI  - TiO2 Phase Junction Electron Transport Layer Boosts Efficiency of Planar
      Perovskite Solar Cells.
AB  - In the planar perovskite solar cells (PSCs), the electron transport layer (ETL)
      plays a critical role in electron extraction and transport. Widely utilized TiO2
      ETLs suffer from the low conductivity and high surface defect density. To address
      these problems, for the first time, two types of ETLs based on TiO2 phase
      junction are designed and fabricated distributed in the opposite space, namely
      anatase/rutile and rutile/anatase. The champion efficiency of PSCs based on phase
      junction ETL is over 15%, which is much higher than that of cells with single
      anatase (9.8%) and rutile (11.8%) TiO2 as ETL. The phase junction based PSCs also
      demonstrated obviously reduced hysteresis. The enhanced performance is discussed
      and mainly ascribed to the excellent capability of carrier extraction, defect
      passivation, and reduced recombination at the ETL/perovskite interface. This work
      opens a new phase junction ETL strategy toward interfacial energy band
      manipulation for improved PSC performance.

PMID- 29593965
TI  - Superlubricity of Graphite Induced by Multiple Transferred Graphene Nanoflakes.
AB  - 2D or 3D layered materials, such as graphene, graphite, and molybdenum disulfide,
      usually exhibit superlubricity properties when sliding occurs between the
      incommensurate interface lattices. This study reports the superlubricity between
      graphite and silica under ambient conditions, induced by the formation of
      multiple transferred graphene nanoflakes on the asperities of silica surfaces
      after the initial frictional sliding. The friction coefficient can be reduced to
      as low as 0.0003 with excellent robustness and is independent of the surface
      roughness, sliding velocities, and rotation angles. The superlubricity mechanism
      can be attributed to the extremely weak interaction and easy sliding between the
      transferred graphene nanoflakes and graphite in their incommensurate contact.
      This finding has important implications for developing approaches to achieve
      superlubricity of layered materials at the nanoscale by tribointeractions.

PMID- 29593966
TI  - Self-Assembled Biomolecular 1D Nanostructures for Aqueous Sodium-Ion Battery.
AB  - Aqueous sodium-ion battery of low cost, inherent safety, and environmental
      benignity holds substantial promise for new-generation energy storage
      applications. However, the narrow potential window of water and the enlarged
      ionic radius because of hydration restrict the selection of electrode materials
      used in the aqueous electrolyte. Here, inspired by the efficient redox reaction
      of biomolecules during cellular energy metabolism, a proof of concept is proposed
      that the redox-active biomolecule alizarin can act as a novel electrode material
      for the aqueous sodium-ion battery. It is demonstrated that the specific capacity
      of the self-assembled alizarin nanowires can reach as high as 233.1 mA h g-1,
      surpassing the majority of anodes ever utilized in the aqueous sodium-ion
      batteries. Paired with biocompatible and biodegradable polypyrrole, this full
      battery system shows excellent sodium storage ability and flexibility, indicating
      its potential applications in wearable electronics and biointegrated devices. It
      is also shown that the electrochemical properties of electrodes can be tailored
      by manipulating naturally occurring 9,10-anthroquinones with various substituent
      groups, which broadens application prospect of biomolecules in aqueous sodium-ion
      batteries.

PMID- 29593967
TI  - Redox-Active Separators for Lithium-Ion Batteries.
AB  - A bilayered cellulose-based separator design is presented that can enhance the
      electrochemical performance of lithium-ion batteries (LIBs) via the inclusion of
      a porous redox-active layer. The proposed flexible redox-active separator
      consists of a mesoporous, insulating nanocellulose fiber layer that provides the
      necessary insulation between the electrodes and a porous, conductive, and redox
      active polypyrrole-nanocellulose layer. The latter layer provides mechanical
      support to the nanocellulose layer and adds extra capacity to the LIBs. The redox
      active separator is mechanically flexible, and no internal short circuits are
      observed during the operation of the LIBs, even when the redox-active layer is in
      direct contact with both electrodes in a symmetric lithium-lithium cell. By
      replacing a conventional polyethylene separator with a redox-active separator,
      the capacity of the proof-of-concept LIB battery containing a LiFePO4 cathode and
      a Li metal anode can be increased from 0.16 to 0.276 mA h due to the capacity
      contribution from the redox-active separator. As the presented redox-active
      separator concept can be used to increase the capacities of electrochemical
      energy storage systems, this approach may pave the way for new types of
      functional separators.

PMID- 29593968
TI  - Engineering a Tumor Microenvironment-Mimetic Niche for Tissue Regeneration with
      Xenogeneic Cancer Cells.
AB  - The insufficient number of cells suitable for transplantation is a long-standing
      problem to cell-based therapies aimed at tissue regeneration. Xenogeneic cancer
      cells (XCC) may be an alternative source of therapeutic cells, but their
      transplantation risks both immune rejection and unwanted spreading. In this
      study, a strategy to facilitate XCC transplantation is reported and their
      spreading in vivo is confined by constructing an engineering matrix that mimics
      the characteristics of tumor microenvironment. The data show that this matrix, a
      tumor homogenate-containing hydrogel (THAG), successfully creates an
      immunosuppressive enclave after transplantation into immunocompetent mice. XCC of
      different species and tissue origins seeded into THAG survive well, integrated
      with the host and developed the intrinsic morphology of the native tissue,
      without being eliminated or spreading out of the enclave. Most strikingly,
      immortalized human hepatocyte cells and rat beta-cells loaded into THAG exert the
      physiological functions of the human liver and rat pancreas islets, respectively,
      in the mouse body. This study demonstrates a novel and feasible approach to
      harness the unique features of tumor development for tissue transplantation and
      regenerative medicine.

PMID- 29593969
TI  - Enabling Photon Upconversion and Precise Control of Donor-Acceptor Interaction
      through Interfacial Energy Transfer.
AB  - Upconverting materials have achieved great progress in recent years, however, it
      remains challenging for the mechanistic research on new upconversion strategy of
      lanthanides. Here, a novel and efficient strategy to realize photon upconversion
      from more lanthanides and fine control of lanthanide donor-acceptor interactions
      through using the interfacial energy transfer (IET) is reported. Unlike
      conventional energy-transfer upconversion and recently reported energy-migration
      upconversion, the IET approach is capable of enabling upconversions from Er3+,
      Tm3+, Ho3+, Tb3+, Eu3+, Dy3+ to Sm3+ in NaYF4- and NaYbF4-based core-shell
      nanostructures simultaneously. Applying the IET in a Nd-Yb coupled sensitizing
      system can also enable the 808/980 nm dual-wavelength excited upconversion from a
      single particle. More importantly, the construction of IET concept allows for a
      fine control and manipulation of lanthanide donor-acceptor interactions and
      dynamics at the nanometer-length scale by establishing a physical model upon an
      interlayer-mediated nanostructure. These findings open a door for the fundamental
      understanding of the luminescence dynamics involving lanthanides at nanoscale,
      which would further help conceive new scientific concepts and control photon
      upconversion at a single lanthanide ion level.

PMID- 29593970
TI  - Compositionally Graded Absorber for Efficient and Stable Near-Infrared
      Transparent Perovskite Solar Cells.
AB  - Compositional grading has been widely exploited in highly efficient Cu(In,Ga)Se2,
      CdTe, GaAs, quantum dot solar cells, and this strategy has the potential to
      improve the performance of emerging perovskite solar cells. However, realizing
      and maintaining compositionally graded perovskite absorber from solution
      processing is challenging. Moreover, the operational stability of graded
      perovskite solar cells under long-term heat/light soaking has not been
      demonstrated. In this study, a facile partial ion-exchange approach is reported
      to achieve compositionally graded perovskite absorber layers. Incorporating
      compositional grading improves charge collection and suppresses interface
      recombination, enabling to fabricate near-infrared-transparent perovskite solar
      cells with power conversion efficiency of 16.8% in substrate configuration, and
      demonstrate 22.7% tandem efficiency with 3.3% absolute gain when mechanically
      stacked on a Cu(In,Ga)Se2 bottom cell. Non-encapsulated graded perovskite device
      retains over 93% of its initial efficiency after 1000 h operation at maximum
      power point at 60  degrees C under equivalent 1 sun illumination. The results
      open an avenue in exploring partial ion-exchange to design graded perovskite
      solar cells with improved efficiency and stability.

PMID- 29593971
TI  - In Situ Synthesis of Vertical Standing Nanosized NiO Encapsulated in Graphene as
      Electrodes for High-Performance Supercapacitors.
AB  - NiO is a promising electrode material for supercapacitors. Herein, the novel
      vertically standing nanosized NiO encapsulated in graphene layers (G@NiO) are
      rationally designed and synthesized as nanosheet arrays. This unique vertical
      standing structure of G@NiO nanosheet arrays can enlarge the accessible surface
      area with electrolytes, and has the benefits of short ion diffusion path and good
      charge transport. Further, an interconnected graphene conductive network acts as
      binder to encapsulate the nanosized NiO particles as core-shell structure, which
      can promote the charge transport and maintain the structural stability.
      Consequently, the optimized G@NiO hybrid electrodes exhibit a remarkably enhanced
      specific capacity up to 1073 C g-1 and excellent cycling stability. This study
      provides a facial strategy to design and construct high-performance metal oxides
      for energy storage.

PMID- 29593972
TI  - Intrinsically High Thermoelectric Performance in AgInSe2 n-Type Diamond-Like
      Compounds.
AB  - Diamond-like compounds are a promising class of thermoelectric materials, very
      suitable for real applications. However, almost all high-performance diamond-like
      thermoelectric materials are p-type semiconductors. The lack of high-performance
      n-type diamond-like thermoelectric materials greatly restricts the fabrication of
      diamond-like material-based modules and their real applications. In this work, it
      is revealed that n-type AgInSe2 diamond-like compound has intrinsically high
      thermoelectric performance with a figure of merit (zT) of 1.1 at 900 K,
      comparable to the best p-type diamond-like thermoelectric materials reported
      before. Such high zT is mainly due to the ultralow lattice thermal conductivity,
      which is fundamentally limited by the low-frequency Ag-Se "cluster vibrations,"
      as confirmed by ab initio lattice dynamic calculations. Doping Cd at Ag sites
      significantly improves the thermoelectric performance in the low and medium
      temperature ranges. By using such high-performance n-type AgInSe2-based
      compounds, the diamond-like thermoelectric module has been fabricated for the
      first time. An output power of 0.06 W under a temperature difference of 520 K
      between the two ends of the module is obtained. This work opens a new window for
      the applications using the diamond-like thermoelectric materials.

PMID- 29593973
TI  - Molybdenum Carbide Nanoparticles Coated into the Graphene Wrapping N-Doped Porous
      Carbon Microspheres for Highly Efficient Electrocatalytic Hydrogen Evolution Both
      in Acidic and Alkaline Media.
AB  - Molybdenum carbide (Mo2C) is recognized as an alternative electrocatalyst to
      noble metal for the hydrogen evolution reaction (HER). Herein, a facile, low
      cost, and scalable method is provided for the fabrication of Mo2C-based
      eletrocatalyst (Mo2C/G-NCS) by a spray-drying, and followed by annealing. As
      prepared Mo2C/G-NCS electrocatalyst displays that ultrafine Mo2C nanopartilces
      are uniformly embedded into graphene wrapping N-doped porous carbon microspheres
      derived from chitosan. Such designed structure offer several favorable features
      for hydrogen evolution application: 1) the ultrasmall size of Mo2C affords a
      large exposed active sites; 2) graphene-wrapping ensures great electrical
      conductivity; 3) porous structure increases the electrolyte-electrode contact
      points and lowers the charge transfer resistance; 4) N-dopant interacts with H+
      better than C atoms and favorably modifies the electronic structures of adjacent
      Mo and C atoms. As a result, the Mo2C/G-NCS demonstrates superior HER activity
      with a very low overpotential of 70 or 66 mV to achieve current density of 10 mA
      cm-2, small Tafel slope of 39 or 37 mV dec-1, respectively, in acidic and
      alkaline media, and high stability, indicating that it is a great potential
      candidate as HER electrocatalyst.

PMID- 29593974
TI  - The Dawn of Lead-Free Perovskite Solar Cell: Highly Stable Double Perovskite
      Cs2AgBiBr6 Film.
AB  - Recently, lead-free double perovskites have emerged as a promising
      environmentally friendly photovoltaic material for their intrinsic thermodynamic
      stability, appropriate bandgaps, small carrier effective masses, and low exciton
      binding energies. However, currently no solar cell based on these double
      perovskites has been reported, due to the challenge in film processing. Herein, a
      first lead-free double perovskite planar heterojunction solar cell with a high
      quality Cs2AgBiBr6 film, fabricated by low-pressure assisted solution processing
      under ambient conditions, is reported. The device presents a best power
      conversion efficiency of 1.44%. The preliminary efficiency and the high stability
      under ambient condition without encapsulation, together with the high film
      quality with simple processing, demonstrate promise for lead-free perovskite
      solar cells.

PMID- 29593975
TI  - Ultraconformable Temporary Tattoo Electrodes for Electrophysiology.
AB  - Electrically interfacing the skin for monitoring personal health condition is the
      basis of skin-contact electrophysiology. In the clinical practice the use of
      stiff and bulky pregelled or dry electrodes, in contrast to the soft body
      tissues, imposes severe restrictions to user comfort and mobility while limiting
      clinical applications. Here, in this work dry, unperceivable temporary tattoo
      electrodes are presented. Customized single or multielectrode arrays are readily
      fabricated by inkjet printing of conducting polymer onto commercial decal
      transfer paper, which allows for easy transfer on the user's skin. Conformal
      adhesion to the skin is provided thanks to their ultralow thickness (<1 um).
      Tattoo electrode-skin contact impedance is characterized on short- (1 h) and long
      term (48 h) and compared with standard pregelled and dry electrodes. The
      viability in electrophysiology is validated by surface electromyography and
      electrocardiography recordings on various locations on limbs and face. A novel
      concept of tattoo as perforable skin-contact electrode, through which hairs can
      grow, is demonstrated, thus permitting to envision very long-term recordings on
      areas with high hair density. The proposed materials and patterning strategy make
      this technology amenable for large-scale production of low-cost sensing devices.

PMID- 29593976
TI  - Hollow TiO2@Co9S8 Core-Branch Arrays as Bifunctional Electrocatalysts for
      Efficient Oxygen/Hydrogen Production.
AB  - Designing ever more efficient and cost-effective bifunctional electrocatalysts
      for oxygen/hydrogen evolution reactions (OER/HER) is greatly vital and
      challenging. Here, a new type of binder-free hollow TiO2@Co9S8 core-branch arrays
      is developed as highly active OER and HER electrocatalysts for stable overall
      water splitting. Hollow core-branch arrays of TiO2@Co9S8 are readily realized by
      the rational combination of crosslinked Co9S8 nanoflakes on TiO2 core via a
      facile and powerful sulfurization strategy. Arising from larger active surface
      area, richer/shorter transfer channels for ions/electrons, and reinforced
      structural stability, the as-obtained TiO2@Co9S8 core-branch arrays show
      noticeable exceptional electrocatalytic performance, with low overpotentials of
      240 and 139 mV at 10 mA cm-2 as well as low Tafel slopes of 55 and 65 mV Dec-1
      for OER and HER in alkaline medium, respectively. Impressively, the electrolysis
      cell based on the TiO2@Co9S8 arrays as both cathode and anode exhibits a
      remarkably low water splitting voltage of 1.56 V at 10 mA cm-2 and long-term
      durability with no decay after 10 d. The versatile fabrication protocol and smart
      branch-core design provide a new way to construct other advanced metal sulfides
      for energy conversion and storage.

PMID- 29593977
TI  - Smart Construction of Integrated CNTs/Li4Ti5O12 Core/Shell Arrays with Superior
      High-Rate Performance for Application in Lithium-Ion Batteries.
AB  - Exploring advanced high-rate anodes is of great importance for the development of
      next-generation high-power lithium-ion batteries (LIBs). Here, novel carbon
      nanotubes (CNTs)/Li4Ti5O12 (LTO) core/shell arrays on carbon cloth (CC) as
      integrated high-quality anode are constructed via a facile combined chemical
      vapor deposition-atomic layer deposition (ALD) method. ALD-synthesized LTO is
      strongly anchored on the CNTs' skeleton forming core/shell structures with
      diameters of 70-80 nm the combined advantages including highly conductive
      network, large surface area, and strong adhesion are obtained in the CC-LTO@CNTs
      core/shell arrays. The electrochemical performance of the CC-CNTs/LTO electrode
      is completely studied as the anode of LIBs and it shows noticeable high-rate
      capability (a capacity of 169 mA h g-1 at 1 C and 112 mA h g-1 at 20 C), as well
      as a stable cycle life with a capacity retention of 86% after 5000 cycles at 10
      C, which is much better than the CC-LTO counterpart. Meanwhile, excellent cycling
      stability is also demonstrated for the full cell with LiFePO4 cathode and CC
      CNTs/LTO anode (87% capacity retention after 1500 cycles at 10 C). These positive
      features suggest their promising application in high-power energy storage areas.

PMID- 29593978
TI  - Quantitative Assessments of Mechanical Responses upon Radial Extracorporeal Shock
      Wave Therapy.
AB  - Although radial extracorporeal shock wave therapy (rESWT) has been widely used to
      treat orthopedic disorders with promising clinical results, rESWT largely relies
      on clinicians' personal experiences and arbitrary judgments, without knowing
      relationships between administration doses and effective doses at target sites.
      In fact, practitioners lack a general and reliable way to assess propagation and
      distribution of pressure waves inside biological tissues quantitatively. This
      study develops a methodology to combine experimental measurements and
      computational simulations to obtain pressure fields from rESWT through
      calibrating and validating computational models with experimental measurements.
      Wave pressures at the bottom of a petri dish and inside biological tissues are
      measured, respectively, by attaching and implanting flexible membrane sensors.
      Detailed wave dynamics are simulated through explicit finite element analyses.
      The data decipher that waves from rESWT radiate directionally and can be modeled
      as acoustic waves generated from a vibrating circular piston. Models are thus
      established to correlate pressure amplitudes at the bottom of petri dishes and in
      the axial direction of biological tissues. Additionally, a pilot simulation upon
      rESWT for human lumbar reveals a detailed and realistic pressure field mapping.
      This study will open a new avenue of personalized treatment planning and
      mechanism research for rESWT.

PMID- 29593979
TI  - The association between pre-hospital antibiotic therapy and subsequent in
      hospital mortality in adults presenting with community-acquired pneumonia: an
      observational study.
AB  - Background: The majority of patients with community acquired-pneumonia (CAP) are
      treated in primary care and the mortality in this group is very low. However, a
      small but significant proportion of patients who begin treatment in the community
      subsequently require admission due to symptomatic deterioration. This study
      compared patients who received community antibiotics prior to admission to those
      who had not, and looked for associations with clinical outcomes. Methods: This
      study analysed the Advancing Quality (AQ) Pneumonia database of patients admitted
      with CAP to 9 acute hospitals in the northwest of England over a 12-month period.
      Results: There were 6348 subjects (mean age 72 [SD 16] years; gender ratio 1:1)
      admitted with CAP, of whom 17% had been pre-treated with antibiotics. The in
      hospital mortality was 18.6% for the pre-treatment group compared to 13.2% in the
      "antibiotic naive" group (p < 0.001). On multivariate analysis, age, male gender
      and antibiotic pre-treatment were predictors of in-hospital mortality along with
      a history of cerebrovascular accident, congestive cardiac failure, dementia,
      renal disease and cancer. After adjustment for CURB-65 score, age, co-morbidities
      and pre-treatment with antibiotics remained as independent risk factors for in
      hospital mortality (OR 1.43, 95% CI 1.19-1.71). Conclusion: CAP patients admitted
      to hospital were more likely to die during admission if they had received
      antibiotics for the same illness pre-admission. Future studies should endeavor to
      determine the mechanisms underlying this association, such as microbiological
      factors and the role of comorbidities. Patients hospitalized with CAP despite
      prior antibiotic treatment in the community require close monitoring.

PMID- 29593980
TI  - Anatomic Posterolateral Corner Reconstruction With Autografts.
AB  - Anatomic posterolateral corner reconstruction reproduces 3 main structures: the
      lateral collateral ligament, the popliteofibular ligament, and the popliteus
      tendon. The LaPrade technique reproduces all 3 main stabilizers. However, it
      requires a long graft, limiting its indication to clinical settings in which
      allograft tissue is available. We propose a surgical procedure that is a
      modification of the LaPrade technique using the same tunnel placement, hamstring
      autografts, and biceps augmentation when necessary. It relies on artificial graft
      lengthening provided by the loop of the suspensory fixation device fixed at the
      anterior tibial cortex. The final reconstruction reproduces the popliteus tendon
      with the bulkiest end of the semitendinosus; the popliteofibular ligament with a
      strand of the semitendinosus and a strand of the gracilis; and the lateral
      collateral ligament with a strand of the semitendinosus and a strand of the
      gracilis, which can also be augmented with a biceps strip.

PMID- 29593981
TI  - Giant cystic degeneration of a uterine leiomyoma in a patient with autosomal
      dominant polycystic kidney disease.
AB  - Objective: To report the management of a large uterine leiomyoma with diffuse
      cystic degeneration in a patient with autosomal dominant polycystic kidney
      disease (ADPKD). Design: Case Report. Setting: Cleveland Clinic Florida,
      Department of Gynecology, Section of Minimally Invasive Gynecologic surgery,
      Weston Florida. Patients: A 52-year old woman with ADPKD with a large abdominal
      mass, abnormal uterine bleeding and symptomatic anemia. Imaging revealed a giant
      intramural cystic lesion of the uterus compressing the inferior vena cava.
      Interventions: Uterine artery embolization and blood transfusion followed by a
      computed tomography guided cyst aspiration were performed on admission to
      alleviate anemia and abdominal pain and distension. Total laparoscopic
      hysterectomy with bilateral salpingectomy was performed in an outpatient setting.
      Main Outcome Measures: Management of large cystic degeneration of leiomyoma.
      Results: Normal recovery from definitive surgery. Surgical pathology confirmed a
      benign, cystically dilated leiomyoma. Conclusion: This case demonstrates the
      management of giant intramural cyst lesion of the uterus using a minimally
      invasive surgical approach, as opposed to emergency surgery via laparotomy.
      Capsule: Large uterine leiomyoma with diffuse cystic degeneration in a patient
      with autosomal dominant polycystic kidney disease, in which step-wise treatments
      allows successful minimally invasive hysterectomy.

PMID- 29593982
TI  - Vaginal evisceration as rare but a serious obstetric complication: A case series.
AB  - Introduction: Gut prolapse through vagina is rare complication with only few
      cases reported in the literature. This article highlights untrained professionals
      induced obstetrical trauma as a cause of vaginal evisceration leading to serious
      but preventable complications. Presentation of Case: Case 1: A 27 years old
      female, P2L0, had full term vaginal delivery of an IUD baby and presented 4 days
      later with small bowel evisceration through posterior vaginal wall. Case 2: A 24
      years old female, P1A1 had underwent unsafe abortion and presented in shock, with
      small bowel evisceration through anterior uterine wall. Case 3: A 26 years
      female, P2A1, underwent evacuation for incomplete abortion and presented with
      omental prolapse through anterior uterine wall. Discussion: Obstetrical trauma
      with associated evisceration of intraabdominal contents is a potentially serious
      complication that requires surgical intervention. General awareness may decrease
      these unsafe practices and thus would have impact in reducing maternal morbidity
      and mortality.

PMID- 29593983
TI  - Intrapartal resection of the double cervix and longitudinal vaginal septum after
      hysteroscopic resection of the complete uterine septum, resulting in a term
      vaginal delivery: A case report.
AB  - Objective: To report a rare uterine anomaly of a septate uterus, double cervix
      and double vagina in patient who conceived spontaneously and delivered vaginaly.
      Design: Case report. Setting: Department of Obstetrics and Gynecology, Zagreb
      University School of Medicine, Clinical Hospital "Sveti Duh", Zagreb, Croatia.
      Patients: A 34-year-old nulligravida who underwent clinical, radiological,
      surgical and intrapartal workup. Interventions: Clinical examination and
      intrapartal surgical resection of vaginal septum followed by vaginal delivery.
      Main Outcome Measures: Description and treatment for a rare Mullerian anomaly and
      a subsequent literature search. Results: Successful intrapartal resection of
      longitudinal vaginal septum and double cervix followed by vaginal delivery
      without complication. Conclusions: Reconstructive surgical procedures may be
      considered for providing spontaneous pregnancies and intrapartal surgical
      technique could be taken into consideration in order to prevent unnecessary
      cesarean sections, upon strict estimation of the obstetrician.

PMID- 29593984
TI  - A Bartholin's gland with nodules and cysts bathed in mucus.
AB  - The most common pathology of the Bartholin's gland is with its draining duct.
      Marsupialisation or fistulisation are the most common therapies. In some women,
      the clinical problem is with the Bartholin's gland itself, being hyperplasia with
      or without duct rupture in the subcutaneous tissue. Presenting symptoms and signs
      of nodular hyperplasia are pain and (nodular or diffuse) swelling especially
      during sexual arousal, or simply a symptomless mass. During surgery, the striking
      features are subcutaneous free-floating mucus and nodular enlargement 'deep' in
      the labium majus. The optimal surgical approach is an excision through an
      incision alongside the labiocrural fold. We describe three cases to provide
      insight into the various clinical presentations and management problems. Nodular
      hyperplasia of Bartholin's gland is easily misdiagnosed because of its rare
      occurrence and diversity of signs and symptoms. An unusual presentation or
      clinical course of disease may indicate nodular hyperplasia.

PMID- 29593985
TI  - Full term viable secondary broad ligament pregnancy - A rare case.
AB  - Broad ligament pregnancy is also known as inter ligamentous pregnancy which is a
      rare form of ectopic pregnancy. Very few successful live births have been
      reported in this condition, where such pregnancies reached term and with live
      birth of a baby. A case of 28 year old primigravida of 35 weeks gestation with
      oligoamnios was referred to our hospital. A right broad ligament pregnancy was
      confirmed after an ultrasound and an MRI. She was taken up for surgery and an
      incision was given on the anterior leaf of the broad ligament and a male live
      fetus was extracted. Placenta was found on the posterior leaf of the broad
      ligament and it was removed without any undue haemorrhage. Uterus was lying
      medial to the sac and was around ten weeks in size. Both mother and baby were
      discharged on seventh postoperative day in good health condition.

PMID- 29593986
TI  - Spontaneous acute intussusception in a pregnant woman.
AB  - Acute intussusception in adults is rare and particularly so in pregnant women.
      Its incidence ranges from 0.067% to 0.0015% (Choi et al., 2005 Choi et al. (2005)
      [1]). The non-specific presenting symptoms may be attributed to the pregnancy
      itself, making the diagnosis difficult. When it happens, however, it causes
      considerable morbidity and mortality for the pregnant woman and the fetus. In
      adults, such intussusceptions are mainly secondary to an intestinal disease and
      frequently a tumor. We present the case of a 21-year-old pregnant woman who was
      diagnosed of spontaneous acute intussusception at nine weeks of gestation and
      therapeutic management.

PMID- 29593987
TI  - Luteal phase support for documented failure of placental steroidogenesis: A case
      report.
AB  - Objective: To report a case of a habitual aborter that had a pregnancy reach near
      term and successfully delivered a viable female infant. Design: Report of a
      unique case of a G10P1 that was successfully able to maintain a pregnancy by
      maintaining serum levels of estradiol and progesterone at or above 200 pg/dL and
      25 ng/dL respectively. This case provides a benchmark for exogenous support of
      estradiol and progesterone throughout pregnancy. Setting: A private advanced
      reproductive center. Patient: 39-year-old G10P1091 diagnosed to have
      antiphospholipid syndrome but continued to have continuous miscarriages despite
      accepted treatment. In addition, 8 products of conception were sent for
      cytogenetic testing and all were found to be normal. Interventions: Examination,
      laboratory studies, imaging, clinical judgment, and knowledge of previous
      treatment failures were used to guide the treatment of this patient. Fertility
      was achieved with continuous supplementation of progesterone, estrogen, LMW
      heparin, and prednisone. Main Outcome Measure: Delivery of viable infant.
      Results: This advanced reproductive age woman had three subsequent pregnancies.
      While compliant with our prescribed protocol, the patient successfully carried
      two pregnancies to viability. Conclusion: Clinicians should be alert to the
      possibility of a luteal phase defect when a patient presents with recurrent
      fertility problems and multiple spontaneous abortions.

PMID- 29593988
TI  - Fowler's syndrome post oocyte retrieval for intracytoplasmic sperm injection.
AB  - Objective: To report a case of Fowler's syndrome after oocyte retrieval. Design:
      Case report. Setting: Tertiary referral center, King Fahad Medical City.
      Patients: A 23-year-old nulligravida with polycystic ovarian syndrome and primary
      infertility underwent oocyte retrieval for intracytoplasmic sperm injection
      (ICSI), and developed Fowler's syndrome (FS). Interventions: Intermittent self
      catheterization, insertion of sacral neuromodulator (SNM). Main outcome measures:
      Restoration of normal voiding. Results: Immediate resolution of patient's
      symptoms after installation of SNM. Conclusions: Fowler's syndrome, although
      rare, may occur post routine oocyte retrieval; Successful restoration of voiding
      and resolution of symptoms is possible with SNM installation in similar patients.

PMID- 29593989
TI  - Postoperative care of symphysiotomy performed for severe shoulder dystocia with
      fetal demise.
AB  - Background: Shoulder dystocia is an obstetric emergency which occurs in 0.2-3% of
      all births ACOG Committee on Practice Bulletins-Obstetrics and The American
      College of Obstetrician and Gynecologists (2002) . Symphysiotomy is a treatment
      option reserved primarily for developing countries where mortality rates of
      Cesarean delivery are 1-2% Monjok et al. (2013) . Case: A G3P2002 with a history
      of two prior vaginal deliveries had a term delivery complicated by a severe
      shoulder dystocia. She underwent emergent symphysiotomy at an outside
      institution, with delivery of a dead macrosomic infant. She was transferred to
      our tertiary care center for further care. Conclusion: Symphysiotomy is rarely
      performed in the United States. We submit our postoperative management to add to
      the literature of this rarely performed obstetric intervention. Precis:
      Symphysiotomy for severe shoulder dystocia is rarely utilized in the United
      States. We describe a case of symphysiotomy done for severe shoulder dystocia at
      an outside institution, and the patient's subsequent care at our institution.

PMID- 29593990
TI  - Successful pregnancy located in a uterine cesarean scar: A case report.
AB  - Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy. Because CSP
      carries a high risk of uterine rupture and life-threatening bleeding, the
      pregnancy should be terminated upon confirmation of diagnosis. There have been
      few reports of CSP with successful delivery. We present a case of CSP under
      expectant management, with delivery via planned cesarean section at 35 weeks of
      gestation. This report suggests that successful pregnancy outcome can be achieved
      in some women with uterine cesarean scar, but further analysis and additional
      studies are required in order to describe the optimal protocol of expectant
      management in CSP.

PMID- 29593991
TI  - Uterine rupture in a primigravid patient with an unscarred bicornuate uterus at
      term.
AB  - Background: Uterine rupture of an unscarred primigravid uterus is an exceedingly
      rare event. Cases of spontaneous rupture of an unscarred bicornuate uterus have
      been reported, but typically occur in the first or second trimester. Case: A 28
      year-old primigravida at 37 weeks gestation with a known bicornuate uterus and no
      prior surgery underwent an emergent cesarean section after presenting with severe
      abdominal pain and signs of fetal compromise. She was found to have a uterine
      rupture with the fetus free in the abdomen accompanied by a large hemoperitoneum.
      Both mother and baby did well postoperatively. Conclusion: Bicornuate uterus may
      be an independent risk factor for uterine rupture, which can occur in primigravid
      patients and at any gestation.

PMID- 29593992
TI  - Intracavitary deposits on Essure(r) hysteroscopic sterilization devices: A case
      report.
AB  - Objective: To study the composition of intracavitary deposits on Essure(r)
      hysteroscopic sterilization devices. Design: Case report. Setting: Reproductive
      Medicine and Gynecology department of a University Hospital. Patients: A 39 years
      old patient presenting with a request for surgical removal of Essure(r)
      sterilization devices. Diagnostic hysteroscopy showed a crystal like white
      deposit attached to one of the devices. Intervention: Diagnostic hysteroscopy and
      surgical removal of Essure(r) devices was performed. The deposits were collected
      and infrared spectroscopy analysis was performed. Main Outcome Measure: Chemical
      composition of the deposits attached to the device. Results: Infrared
      spectroscopy of the material showed patterns conclusive with calcite (calcium
      carbonate, CaCO3). Conclusion: Until now, it is not clear if there is a
      relationship between reported complaints and formation of calcite deposits on
      Essure(r). Capsule: Infrared spectroscopy of deposits on Essure(r) devices showed
      a pattern conclusive with calcite. The relationship between reported complaints
      and the formation of calcite deposits on Essure(r) remains unclear.

PMID- 29593993
TI  - Fetal primary hydrothorax with spontaneous resolution.
AB  - Fetal primary hydrothorax is a rare congenital anomaly with an estimated
      incidence of 1:10.000-15.000 pregnancies, with an unpredictable clinical course,
      ranging from spontaneous resolution to fetal death. We present a case of a
      unilateral fetal pleural effusion identified at 35th gestational week. A 37 year
      old woman (G2P1) presented to our routine term pregnancy evaluation. The
      pregnancy had been otherwise uneventful. At ecographic evaluation a large
      anechogenic fluid collection was identified in the right fetal hemithorax, with
      atelectasis of right lung, displacing the heart and mediastinal structures to the
      contralateral hemithorax. Hydramnios was also identified. No other structural
      abnormalities were detected, as no signs of hydrops. Fetal biometry was
      compatible with gestational age. Fetal ecochardiogram was structurally and
      functionally normal. Doppler evaluation of the peak systolic velocity in the
      middle cerebral artery was normal. Screening for congenital infections was
      negative. Complete blood cell count, blood type and antibody screening rulled-out
      immune hydrops. Karyotype analysis was not performed as family decision. Serial
      ecographic re-evaluations showed a progressive volume decrease and at the 38th
      week there was total resolution of the effusion. A C-section was performed at the
      39th week. A live female infant was born weighing 3205 g, with no need of
      ventilatory support. One year post-partum follow-up evaluation confirmed the
      child was healthy. Spontaneous regression has been reported to occur in 9-22% of
      primary fetal hydrothoraxes, but the features predicting a better prognosis
      remain difficult to define. Unilateral effusion, spontaneous resolution and
      absence of hydrops at the age of diagnosis seem to be indicators of better
      outcome.

PMID- 29593994
TI  - Myrrh for treatment of severe vulvar edema in ovarian hyperstimulation syndrome.
AB  - Background: Severe vulvar edema is a rare entity occurring with ovarian
      hyperstimulation syndrome. This edema can be incapacitating; causing pain and
      limited patient mobility. With the usual conservative approach, vulvar edema can
      take several days to resolve. Aim: The aim of this case report is to describe the
      use of local myrrh for the management of severe vulvar edema associated with
      ovarian hyperstimulation syndrome. Case Presentation: 29-year-old female with
      severe vulvar edema associated with ovarian hyperstimulation syndrome.
      Conclusion: Local myrrh application for severe vulvar edema in ovarian
      hyperstimulation syndrome resulted in substantial improvement, and with further
      studies, myrrh could be used as an option for the management of vulvar edema.

PMID- 29593996
TI  - Trauma-induced delivery: A case report.
AB  - The term "birth trauma" is one that is well ingrained into the lexicon of medical
      providers. There is ample information of the types of injuries that are incurred
      during the birth process. However, there is no uniformed term for the process of
      an unforeseen act that leads to a precipitous birth. We would like to show a case
      report of such an act. The infant's injuries were sustained while in utero and
      the trauma induced a medical team to deliver the infant due to non-reassuring
      heart tones. Also, we would like to introduce the term of "trauma-induced
      delivery" into the medical literature as a way to describe similar types of
      deliveries that are influenced by factors related to physical forces applied to
      the mother's body, either intentional or unintentional.

PMID- 29593995
TI  - Late-onset endometrial ablation failure.
AB  - Endometrial ablation, first reported in the 19th century, has gained wide
      acceptance in the gynecologic community as an important tool for the management
      of abnormal uterine bleeding when medical management has been unsuccessful or
      contraindicated. The introduction of global endometrial ablation (GEA) devices
      beginning in 1997 has provided unsurpassed safety addressing many of the concerns
      associated with their resectoscopic predecessors. As of this writing the GEA
      market has surpassed a half-million devices in the United States per annum and
      has an expected compound annual growth rate (CAGR) projected to be 5.5% from 2016
      to 2024. While the short term safety and efficacy of these devices has been
      reported in numerous clinical trials we only recently are becoming aware of the
      high incidence of late-onset endometrial ablation failures (LOEAFs) associated
      with these procedures. Currently, about a quarter of women who undergo a GEA
      procedure will eventually require a hysterectomy while an unknown number have
      less than satisfactory results. In order to reduce these suboptimal outcomes
      physicians must better understand the etiology and risk factors that predispose a
      patient toward the development of LOEAF as well as current knowledge of patient
      and procedure selection for EA as well as treatment options for these delayed
      complications.

PMID- 29593997
TI  - Hereditary leiomyomatosis and renal cell cancer: Cutaneous lesions & atypical
      fibroids.
AB  - Objective: To report a diagnosis of hereditary leiomyomatosis and renal cell
      cancer (HLRCC) syndrome following initial presentation with multiple cutaneous
      lesions. Design: Case report. Design classification: N/A. Setting: Academic
      tertiary care center. Patients: 27-year-old nulligravid woman who presented with
      multiple red-brown lesions on her skin found to have cutaneous and uterine
      leiomyoma. Interventions: Biopsy of cutaneous lesions and fertility sparing robot
      assisted laparoscopic myomectomy (RALM). Main outcome measuress: Histological
      assessment of uterine leiomyoma. Resultss: Pathologic examination of uterine
      leiomyoma revealed diffuse atypia and fumarate hydratase loss phenotype
      concerning for genetic syndrome. Follow-up DNA sequencing via Sanger sequencing
      confirmed a pathogenetic R2333H mutation consistent with HLRCC. Conclusions:
      Consideration of HLRCC on differential diagnosis when patients present with
      cutaneous nodules and atypical or early onset uterine leiomyoma provides
      opportunity for early surveillance, family member testing, and more thoughtful
      surgical planning. Precis: 27-year-old woman with multiple cutaneous lesions is
      found to have uterine leiomyomas and undergoes robotic myomectomy. Genetic
      testing of uterine leiomyomas reveals mutation in fumarate hydratase, etiologic
      in hereditary leiomyomatosis and renal cell cancer (HLRCC).

PMID- 29593998
TI  - Publication of medical case reports and consent.

PMID- 29593999
TI  - A case of uterus-like mass of the ovary associated with endometriosis.
AB  - *Coelomic metaplasia is considered to be one of the mechanisms resulting in
      endometriosis.*Intense ceolomic metaplasia resulted in a uterine like mass (ULM)
      acquiring the structural integrity of a miniature uterus.*ULM might be considered
      a rare manifestation in the spectrum of endometriosis development.

PMID- 29594000
TI  - Nonimmune hydrops fetalis due to autosomal recessive hereditary spherocytosis.
AB  - Background: Hereditary spherocytosis is the most common form of inherited
      hemolytic anemia and is characterized by a structural defect in the RBC membrane.
      The disorder is commonly inherited in an autosomal dominant fashion and leads to
      a mild to moderate anemia. The autosomal recessive form of hereditary
      spherocytosis is rarely reported in association with fetal anemia and hydrops
      fetalis. Case: A 25 year old G5 P2112 at 25 2/7 weeks gestation presents with
      severe fetal anemia and nonimmune hydrops fetalis requiring multiple fetal
      intrauterine transfusions. After delivery, the neonate required several double
      volume exchange transfusions and ultimately was diagnosed with autosomal
      recessive hereditary spherocytosis weeks after birth. The neonate was identified
      to have a rare homozygous genetic mutation, SPTA1c.6154delG, which leads to
      absent production of normal alpha-spectrin. Conclusion: The case highlights the
      importance of considering less common genetic mutations involving the RBC
      structural proteins when patients present with severe fetal anemia and nonimmune
      hydrops fetalis.

PMID- 29594001
TI  - Urinary ascites in late onset of bladder injury post laparoscopic hysterectomy.
AB  - Urinary tract injuries are unfortunate complications of pelvic surgery. With the
      increasing popularity of minimally invasive surgery, a thorough understanding of
      electrosurgical instrumentation and their thermal spread is important to reduce
      patient injuries. The index patient was a 50 year old woman who underwent a
      supracervical hysterectomy 5 years prior to her presentation with pelvic pain and
      dysuria. When her symptoms failed to improve despite antibiotic and analgesic
      therapy, an abdominal CT scan revealed an ovarian cyst and ascites. A subsequent
      laparoscopy disclosed the presence of a bladder fistula and a diagnosis of
      urinary ascites was made. The patient then underwent a subsequent bladder fistula
      repair. Vesicoperitoneal fistulae (VPF) are rare and should be included in the
      differential diagnosis of the patient with acute onset ascites following
      gynecologic surgery. This case is the first case report of a VPF occurring 5
      years following surgery.

PMID- 29594002
TI  - Obstetric Management of Delayed-Interval Delivery.
AB  - The delayed-interval delivery is a rare, flexible and complex procedure. In light
      of these facts, there is no consensus on the best approach to achieve it
      successfully. This case report is of an asynchronous delivery, in a twin
      pregnancy, with a 32-day interval between births of siblings. Our obstetric
      management at a critical gestational age improved the outcome of the second
      newborn. The probability of success of delayed-interval delivery depends on the
      proper selection of the candidates, the appropriate active management and the
      continuous monitoring for early detection of complications.

PMID- 29594003
TI  - Snake bite in third trimester of pregnancy with systemic envenomation and
      delivery of a live baby in a low resource setting: A case report.
AB  - Background: Snake bite in the third trimester of pregnancy with late
      presentation, systemic envenomation; disseminated intravascular coagulopathy and
      delivery of a live neonate is uncommon in a low resource setting. Case: We
      present a 22 year old unbooked Gravida 3 Para 1+ 1 1alive lentiviral positive
      woman at 32 weeks gestation with snake bite, leg swelling, vaginal bleeding and
      labour pains. At presentation, there were anemia, tachycardia, hypotension; a
      gravid uterus with a single fetus in longitudinal lie, cephalic presentation,
      regular fetal heart rate and cervical dilatation of 3 cm. Preterm labour with
      antepartum hemorrhage due to venomous snake bite was diagnosed. Multidisciplinary
      management instituted led to the survival of both mother and baby. Conclusion: In
      resource constrained setting, disseminated intravascular coagulopathy arising
      from systemic envenomation due to snake bite in pregnancy could be challenging.
      Obstetric outcome depends on the degree of envenomation, gestational age at
      presentation, timing, duration and quality of treatment.

PMID- 29594004
TI  - Publication of medical case reports and the CARE guidelines.

PMID- 29594005
TI  - Tubercular uterocutaneous fistula after caesarean section: A case report.
AB  - A 29-year-old patient had undergone an elective lower-segment caesarean section
      (LSCS) five months previously at a district hospital. The operation and the
      immediate postoperative period were uneventful. After five months she presented
      back with a fistulous opening. A fistulogram revealed a connection between the
      uterus and the skin. Fistulous tract excision was planned. Intraoperatively there
      was communication between the skin and the uterine cavity, with extensive
      necrosis of the uterine wall. The patient gave her informed consent for excision
      of the fistulous tract and/or total abdominal hysterectomy. During surgery, it
      was deemed that there was no scope for excision, so the decision was made for a
      total abdominal hysterectomy. Histopathological examination confirmed
      tuberculosis and the patient responded well to anti-tubercular drugs. This case
      report describes a rare presentation of tubercular uterocutaneous fistula after
      caesarean section.

PMID- 29594006
TI  - Postpartum septic pelvic thrombophlebitis after caesarean delivery: a case
      report.
AB  - Septic pelvic thrombophlebitis is a rare puerperal complication. It is an
      important differential diagnosis of postpartum fever and abdominal pain and
      although the condition is well known its diagnosis can be challenging. We report
      a case of a 41-year-old woman with fever and right abdominal pain three days
      after an uncomplicated caesarean delivery. Clinical, laboratory and imaging exams
      were unremarkable and the patient was treated for endometritis. In the absence of
      improvement despite an antibiotic adjustment, a clinical diagnosis of septic
      pelvic thrombophlebitis was made, and the patient presented a good response to
      anticoagulation in conjunction with broad-spectrum antibiotic therapy.

PMID- 29594007
TI  - Heterotopic interstitial pregnancy: A case report.
AB  - Introduction: Before the advent of assisted reproductive technologies, the
      incidence of heterotopic pregnancy was estimated to be in 1 out of 30,000
      pregnancies in the United States. With interstitial pregnancy comprising only
      2.4% of ectopic pregnancies, spontaneous heterotopic interstitial pregnancies are
      exceedingly rare. Case: A 27-year-old pregnant woman (gravida 3 para 1011) with a
      history of one prior term vaginal delivery and a spontaneous abortion in the
      first trimester presented to the emergency department with abdominal pain and a
      positive home pregnancy test. Transvaginal ultrasound confirmed heterotopic
      pregnancy and she underwent operative management, at which point a ruptured
      interstitial pregnancy was identified. Conclusion: Heterotopic and interstitial
      pregnancies are rare and to see them together in a spontaneous pregnancy is
      virtually unique. The case report describes our management of this rarely seen
      condition.

PMID- 29594008
TI  - Pregnancy in a woman with untreated bladder exstrophy: a case report.
AB  - Objective: To report the management of urinary tract obstruction and infection in
      a pregnant woman with unrepaired bladder exstrophy. Case Report: A 27-year-old
      pregnant woman with unrepaired bladder exstrophy was referred to our hospital
      with a complaint of bilateral flank pain in the second trimester. After two
      dimensional abdominal ultrasound, magnetic resonance imaging and a urine
      analysis, she was diagnosed with an upper urinary tract infection due to ureteral
      obstruction secondary to unrepaired congenital bladder exstrophy and an
      intrauterine pregnancy. J-tube insertion was performed after locating the
      ureteral orifices and antibiotics were administered. Symptoms rapidly resolved.
      She delivered a normal male infant by caesarean section at 34 weeks of gestation.
      Conclusion: Standard urological management of the ureteral obstruction in
      pregnancy was successful in this extreme case of unrepaired bladder exstrophy
      associated with an intrauterine pregnancy. The perinatal outcome was good.

PMID- 29594009
TI  - Ovarian thrombosis and uterine synechiae after arterial embolization for a late
      postpartum haemorrhage.
AB  - Background: We report two unusual separate complications after uterine artery
      embolization for a late postpartum haemorrhage. This report appeared important to
      us in view of the apparent absence of any other publications on this topic. Case
      presentation: We report the case of a 25-year-old woman, gravida 3, para 1,
      admitted for uterine bleeding 7 days after a spontaneous delivery at term, in our
      university hospital. A suction curettage and then, after persistent bleeding,
      uterine artery embolization were necessary. Immediately after the embolization, a
      bilateral ovarian thrombosis occurred, subsequently followed by amenorrhea, due
      to uterine synechiae, and depression. Hysteroscopic surgery was performed to
      remove the adhesions. A complete work-up for thrombophilia showed a heterozygous
      mutation of the factor V gene R506Q. The pathology examination found
      subinvolution of the placental bed. One month after treatment of the synechiae
      (and insertion of a copper IUD for contraception), the woman's menstrual cycle
      returned to normal. Her clinical examination 19 months later was normal.
      Conclusions: This case teaches us that one rare complication can hide another! It
      is important to consider the diagnosis of subinvolution of the placental bed in
      cases of late PPH and to know the complications associated with vascular artery
      embolization in order to provide the most rapid and least invasive treatment.

PMID- 29594010
TI  - Colorectal cancer presenting as tuboovarian abscess in a 40 year old patient with
      previous tubal occlusion.
AB  - Background: Although pelvic inflammatory disease can be seen after tubal
      occlusion, tuboovarian abscess is rare, with only 38 cases reported since 1975
      [1]. The differential diagnosis of tuboovarian abscess after tubal occlusion
      should include non-infectious and non-gynecologic etiology, particularly as women
      age [2]. Case: A 40 year old multiparous woman with a distant history of tubal
      occlusion, presented with pelvic pain and suspected right tuboovarian abscess
      with air on CT scan. A colonic stricture was also seen, warranting further
      evaluation, which revealed a left tuboovarian abscess which had fistulized from a
      bowel perforation secondary to colorectal cancer. Conclusion: Tuboovarian abscess
      is rare after tubal occlusion. These patients should be evaluated specifically
      for nongynecologic etiology, including colorectal cancer. Radiologic studies can
      be misleading, and surgical exploration should be strongly considered if a woman
      with a history of tubal occlusion presents with a presumptive tuboovarian
      abscess, particularly if the abscess contains air.

PMID- 29594011
TI  - Ulcus vulvae acutum - A case of genital ulcers in adolescent girl.
AB  - Ulcus vulvae acutum is a rare clinical condition characterized by the presence of
      multiple acute painful genital ulcers of non-venereal origin associated with
      systemic symptoms in young women. The aetiopathogenesis of the disease is not
      fully understood, although recent reports have associated it with the Epstein
      Barr virus. Diagnosis is difficult and generally made by exclusion after venereal
      diseases, and autoimmune, inflammatory, traumatic, and neoplastic causes. We
      describe a case of adolescent female with an episode of ulcus vulvae acutum
      associated with infectious mononucleosis. The diagnosis was supported by the
      clinical symptoms, elevated circulating levels of liver enzymes, positive EBV
      serology, cervical and inguinal lymphadenomegaly, and hepatosplenomegaly. The
      patient presented a history of aphthous stomatitis. Negative Pathergy test and
      the absence of any other related symptoms allowed us to exclude the Behchet
      syndrome. Lesions healed with no sequelae or recurrences.

PMID- 29594012
TI  - Prostate cancer screening and active surveillance in the Western world.

PMID- 29594013
TI  - How to improve duration and quality of life in men?

PMID- 29594014
TI  - Screening for prostate cancer: are organized screening programs necessary?
AB  - Already in 1991 when the prostate-specific antigen (PSA) test was proposed as a
      diagnostic test, screening for prostate cancer (PCa) was considered controversial
      due to the considerable risk of detecting latent PCa. Randomised controlled
      trials were initiated to assess the potential of PSA-based screening in reducing
      disease-specific mortality. Harms and benefit were closely monitored and both
      were confirmed. A reduction in mortality was seen and at the same time the
      initial fear of unnecessary testing and over diagnosis became reality. This
      triggered professional organizations to adapt their guidelines and to focus on
      shared decision making (SDM) and selective screening for those men considered at
      high risk. Unfortunately implementation of guidelines into daily clinical
      practice is bothersome. As a result many men are being (re)tested while not being
      at risk and the potential benefit being unclear. This raises the question on
      whether PSA screening should be organized in controlled programs. While the PSA
      test will remain the mainstay of PCa early detection many other additional tests
      (biomarkers/imaging) are currently being tested in large population-based
      initiatives as a first step to organized programs in selective groups of men.

PMID- 29594015
TI  - Prostate cancer screening: what can we learn from randomised trials?
AB  - In this article, the principle of randomised trials are first described and then
      prostate cancer screening trials published to date are evaluated based on these
      principles. A summary of the randomised prostate cancer screening is provided.
      The conclusion that can be made from the results of the screening trials, as well
      as limitations of the evidence and open questions are outlined in the end.

PMID- 29594016
TI  - Head-to-head comparison of prostate cancer risk calculators predicting biopsy
      outcome.
AB  - Background: Multivariable risk calculators (RCs) predicting prostate cancer (PCa)
      aim to reduce unnecessary workup (e.g., MRI and biopsy) by selectively
      identifying those men at risk for PCa or clinically significant PCa (csPCa)
      (Gleason >=7). The lack of an adequate comparison makes choosing between RCs
      difficult for patients, clinicians and guideline developers. We aim to perform a
      head-to-head comparison of seven well known RCs predicting biopsy outcome.
      Methods: Our study comprised 7,119 men from ten independent contemporary cohorts
      in Europe and Australia, who underwent prostate biopsy between 2007 and 2015. We
      evaluated the performance of the ERSPC RPCRC, Finne, Chun, ProstataClass,
      Karakiewicz, Sunnybrook, and PCPT 2.0 (HG) RCs in predicting the presence of any
      PCa and csPCa. Performance was assessed by discrimination, calibration and net
      benefit analyses. Results: A total of 3,458 (48%) PCa were detected; 1,784 (25%)
      men had csPCa. No particular RC stood out predicting any PCa: pooled area under
      the ROC-curve (AUC) ranged between 0.64 and 0.72. The ERSPC RPCRC had the highest
      pooled AUC 0.77 (95% CI: 0.73-0.80) when predicting csPCa. Decision curve
      analysis (DCA) showed limited net benefit in the detection of csPCa, but that can
      be improved by a simple calibration step. The main limitation is the
      retrospective design of the study. Conclusions: No particular RC stands out when
      predicting biopsy outcome on the presence of any PCa. The ERSPC RPCRC is superior
      in identifying those men at risk for csPCa. Net benefit analyses show that a
      multivariate approach before further workup is advisable.

PMID- 29594017
TI  - Multivariable risk-based patient selection for prostate biopsy in a primary
      health care setting: referral rate and biopsy results from a urology outpatient
      clinic.
AB  - Background: According to their guidelines, Dutch general practitioners (GPs)
      refer men with prostate-specific antigen (PSA) level >=3.0 ng/mL to the urologist
      for risk-based patient selection for prostate biopsy using the Rotterdam Prostate
      Cancer Risk Calculator (RPCRC). Use of the RPCRC in primary care could optimize
      the diagnostic pathway even further by reducing unnecessary referrals. To
      investigate this, we calculated the risk and assessed the rate of men referred to
      the urologist with PSA level >=3.0 ng/mL by implementing the RPCRC in a primary
      health care setting. Methods: In January 2014, an exploratory study was initiated
      in collaboration with the primary health care facility of the GP laboratory in
      Rotterdam. GPs were given the possibility to refer men with a suspicion of
      prostate cancer (PCa) or a screening wish to this primary care facility (STAR
      SHL) where further assessment was performed by specially trained personnel. Risk
      based advice on referral to the urologist was given to the GP on the basis of the
      RPCRC results. If requested, advice on the treatment of lower urinary tract
      symptoms (LUTS) was provided. All men signed informed consent. Results: Between
      January 2014 and September 2017, a total of 243 men, median age 64 [interquartile
      range (IQR), 57-70] years were referred for a consultation at the primary care
      facility. Of the 108 men with PSA level >=3.0 ng/mL and a referral related to
      PCa, GPs were advised to refer 58 men to the urologist (54%). Of the men with
      available follow-up (FU) data [n=187, median FU, 16 (IQR, 9-25) months] 54 men
      were considered high-risk (i.e., had an elevated risk of PCa as calculated by the
      RPCRC). Of these men, 51 (94%) were actually referred to secondary care by their
      GP, and so far 38 men underwent biopsy. PCa was detected in 30 men [47% had
      Gleason score (GS) >=3+4 PCa], translating to an overall positive predictive
      value (PPV) of 79%. Within the available FU time, 2 out of 38 (5%) men with PSA
      level >=3.0 ng/mL which were considered low-risk have been diagnosed with GS 3+3
      PCa. Conclusions: Risk-stratification with the RPCRC in a primary health care
      setting could prevent almost half of referrals of men with PSA level >=3.0 ng/mL
      to the urologist. In more than three-quarters of men referred for prostate
      biopsy, the suspicion of PCa was confirmed and almost half of men had clinically
      significant PCa (GS >=3+4 PCa). These data show a huge potential for
      multivariable risk-stratification in primary care.

PMID- 29594019
TI  - Stopping screening, when and how?
AB  - Screening for prostate cancer (PC) is still controversial despite randomized
      trials has found that PC mortality is decreased. The major concern is the high
      rate of over-diagnosis and subsequent harms that may follow in many men who never
      would have had any symptoms during life-time if not screened. The high rate of
      over-diagnosis is driven by the large reservoir of small non-significant cancers
      that increases with age and found in more than half of men over 70 years, the low
      specificity of prostate specific antigen (PSA) but also by current "blind" biopsy
      technique that risk accidentally to hit these small non-significant cancers. The
      risk of over-diagnosis is increasing with age and the trade-off by screening men
      in high age is probably higher. At what age harms exceeds benefits is not
      established but modelling studies has demonstrated that after 65-70 years the
      quality adjusted life-years (QALYs) gained are decreasing but still on the
      positive side if screening is continued up to 75 years. A dilemma is that most PC
      deaths occur in men after the age 80 and the effect of screening seems not to
      last as long as was thought, already 10 years after termination of screening PC
      mortality has caught up in the screening arm to a level similar to that in the
      control group. In the European Randomised Study of Screening for Prostate Cancer
      (ERSPC) screening was terminated between 71 and 75 years and the first effect of
      screening on mortality was discernible after 7 years and has been relatively
      stable around 20% since 9 years after study start. It seems questionable from any
      standpoint to invite men for screening with an expected life length below 10
      years, which is the expected life-length of an averaged 78-year-old man in 2018.
      However, the balance between harms and benefits specifically in the age 70-80
      need more attention as also costs need. Permanent side-effects from (unnecessary)
      treatments and their impact on quality of life must be evaluated better and
      related to age and individual variations. In future better screening methods with
      more specific markers and introduction of imaging will hopefully decrease the
      present large risk of over-diagnosis in elderly men and thereby expand efficient
      screening to men in the age group >70 who actually is the high risk group of
      dying from PC.

PMID- 29594018
TI  - Prostate cancer screening-when to start and how to screen?
AB  - Prostate-specific antigen (PSA) screening reduces prostate cancer (PCa)
      mortality; however such screening may lead to harm in terms of overdiagnosis and
      overtreatment. Therefore, upfront shared decision making involving a discussion
      about pros and cons between a physician and a patient is crucial. Total PSA
      remains the most commonly used screening tool and is a strong predictor of future
      life-threatening PCa. Currently there is no strong consensus on the age at which
      to start PSA screening. Most guidelines recommend PSA screening to start no later
      than at age 55 and involve well-informed men in good health and a life expectancy
      of at least 10-15 years. Some suggest to start screening in early midlife for men
      with familial predisposition and men of African-American descent. Others suggest
      starting conversations at age 45 for all men. Re-screening intervals can be risk
      stratified as guided by the man's age, general health and PSA-value; longer
      intervals for those at lower risk and shorter intervals for those at higher risk.
      Overdiagnosis and unnecessary biopsies can be reduced using reflex tests.
      Magnetic resonance imaging in the pre-diagnostic setting holds promise in pilot
      studies and large-scale prospective studies are ongoing.

PMID- 29594020
TI  - What is an acceptable false negative rate in the detection of prostate cancer?
AB  - Background: In prostate cancer (PCa) screening men and their physicians aim to
      rule out the presence of potentially life threatening PCa. To date, prostate
      specific antigen (PSA) testing and systematic prostate biopsy (Bx)-in case of an
      elevated PSA-are still the main modes of PCa detection. Often uncertainty remains
      when a PSA-test is <3.0 ng/mL or a Bx shows a benign result, leading to the
      continuous repeating of procedures. Here we assess the potential consequences of
      false negatives by studying follow-up data of a purely PSA-based approach with
      applying sextant Bx, an approach considered to have a high risk of missing PCa
      diagnosis. Methods: Our study population consisted of 19,970 men from the ERSPC
      project section Rotterdam, initially screened in 1993-1999. We assessed
      clinically significant Gleason >=3+4 PCa (csPCa) diagnosis within the 4-year
      screening interval and subsequent screening round 4 years later in men having a
      PSA <3.0 ng/mL at initial screening (no Bx) and men with Bx (PSA >3.0 ng/mL), but
      no PCa detected at that time. In addition, we addressed PCa mortality and PCa
      diagnosis for men with a negative PSA test and negative Bx, who were retested
      every 4 years covering a 15-year follow-up. Results: A total of 14,935 men had
      PSA <3.0 ng/mL in the initial screening round, of whom 75 (0.5%) were diagnosed
      with csPCa at a subsequent screening examination and 2 (<0.1%) in the 4-year
      screening interval. For 2,260 men with a previously negative Bx at first
      screening, the figures were 17 (0.8%) and 2 (0.1%) respectively. Indolent PCa
      (Gleason <=3+3) was diagnosed in 312 (2%) men with PSA <3.0 ng/mL initially and
      115 (5%) men with initial negative Bx. After a 15-year follow-up, 45 (0.3%) PCa
      deaths occurred in men with initially low PSA, and 29 men (0.2%) had metastasis.
      For men with negative Bx, 11 (0.5%) PCa deaths occurred and 4 (0.2%) experienced
      metastasis. Conclusions: The false negative rates for men with PSA <3.0 ng/mL and
      negative sextant Bx are extremely low but not negligible. Proper risk
      stratification before deciding to biopsy is expected to hardly miss any clinical
      significant PCa diagnosis. This is especially relevant with the increased use of
      the relatively expensive multi-parametric magnetic resonance imaging (mpMRI)
      guided targeted Bx procedures.

PMID- 29594021
TI  - Men with a susceptibility to prostate cancer and the role of genetic based
      screening.
AB  - Prostate cancer is the second most common malignancy affecting men worldwide, and
      the commonest affecting men of African descent. Significant diagnostic and
      therapeutic advances have been made in the past decade. Improvements in the
      accuracy of prostate cancer diagnosis include the uptake of multi-parametric MRI
      and a shift towards targeted biopsy. We also now have more life-prolonging
      systemic and hormonal therapies for men with advanced disease at our disposal
      than ever before. However, the development of robust screening tools and targeted
      screening programs has not followed at the same pace. Evidence to support
      population-based screening remains unclear, with the use of PSA as a screening
      test limiting our ability to discriminate between clinically significant and
      insignificant disease. Prostate cancer has a large heritable component. Given
      that most men without risk factors have a low lifetime risk of developing lethal
      prostate cancer, much work is being done to further our knowledge of how we can
      best screen men in higher risk categories, such as those with a family history
      (FH) of the disease or those of African ancestry. These men have been reported to
      carry upwards of a two-fold increased risk of developing the disease at an
      earlier age, with evidence suggesting poorer survival outcomes. In men with a FH
      of prostate cancer, this is felt to be due to rare, high-penetrance mutations and
      the presence of multiple, common low penetrance alleles, with men carrying
      specific germline mutations in the BRCA and other DNA repair genes at
      particularly high risk. To date, large scale genome-wide association studies
      (GWAS) have led to the discovery of approximately 170 single nucleotide
      polymorphisms (SNPs) associated with prostate cancer risk, allowing over 30% of
      prostate cancer risk to be explained. Genomic tests, utilising somatic (prostate
      biopsy) tissue can also predict the risk of unfavourable pathology, biochemical
      recurrence and the likelihood of metastatic disease using gene expression.
      Targeted screening studies are currently under way in men with DNA repair
      mutations, men with a FH and those of Afro-Caribbean ethnicity which will greater
      inform our understanding of disease incidence and behaviour in these men,
      treatment outcomes and developing the most appropriate screening regime for such
      men. Incorporating a patient's genetic mutation status into risk algorithms
      allows us an opportunity to develop targeted screening programs for men in whom
      early cancer detection and treatment will positively influence survival, and in
      the process offer male family members of affected men the chance to be counselled
      and screened accordingly.

PMID- 29594022
TI  - MRI in early prostate cancer detection: how to manage indeterminate or equivocal
      PI-RADS 3 lesions?
AB  - This review focuses on indeterminate lesions on prostate magnetic resonance
      imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index
      lesion in the diagnostic work-up is significant, varying between one in three
      (32%) to one in five (22%) men, depending on patient cohort of first biopsies,
      previously negative biopsies, and active surveillance biopsies. A management
      strategy must be developed for this group of men with an indeterminate suspicion
      of having clinically significant prostate cancer (csPCa). Currently available
      data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3
      lesions vary between patients groups from one in five (21%) to one in six (16%),
      depending on previous biopsy status. Although this prevalence is lower in
      comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of
      men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore
      be adequately managed. In general, the clinical approach of using a threshold of
      PI-RADS >=4 instead of PI-RADS >=3 to select MRI for targeted biopsies is not
      supported by data from our explorative literature search using current
      definitions of csPCa. A possible adaptation to the threshold of PI-RADS >=4 in
      combination with other clinical markers could be considered within an active
      surveillance protocol, where the balance between the individual risk of missing
      csPCa and the constant process of repeating prostate biopsies is crucial. In the
      future, improvements in MR imaging and interpretation, combined with molecular
      biomarkers and multivariate risk models will all be employed in prostate cancer
      detection and monitoring. These combinations will aid decision-making in
      challenging circumstances, such as unclear and diagnostic equivocal results for
      csPCa at early detection.

PMID- 29594023
TI  - Active surveillance for prostate cancer: a systematic review of contemporary
      worldwide practices.
AB  - In the last decade, active surveillance (AS) has emerged as an acceptable choice
      for low-risk prostate cancer (PC), however there is discordance amongst large AS
      cohort studies with respect to entry and monitoring protocols. We systematically
      reviewed worldwide AS practices in studies reporting >=5 years follow-up. We
      searched PubMed and Medline 2000-now and identified 13 AS cohorts. Three key
      areas were identified: (I) patient selection; (II) monitoring protocols; (III)
      triggers for intervention-(I) all studies defined clinically localised PC
      diagnosis as T2b disease or less and most agreed on prostate-specific antigen
      (PSA) threshold (<10 ug/L) and Gleason score threshold (3+3). Inconsistency was
      most notable regarding pathologic factors (e.g., number of positive cores); (II)
      all agreed on PSA surveillance as crucial for monitoring, and most agreed that
      confirmatory biopsy was required within 12 months of initiation. No consensus was
      reached on optimal timing of digital rectal examination (DRE), general health
      assessment or re-biopsy strategies thereafter; (III) there was no universal
      agreement for intervention triggers, although Gleason score, number or percentage
      of positive cancer cores, maximum cancer length (MCL) and PSA doubling time were
      used by several studies. Some also used imaging or re-biopsy. Despite consistent
      high progression-free/cancer-free survival and conversion-to-treatment rates,
      heterogeneity exists amongst these large AS cohorts. Combining existing evidence
      and gathering more long-term evidence [e.g., the Movember's Global AS database or
      additional information on use of magnetic resonance imaging (MRI)] is needed to
      derive a broadly supported guideline to reduce variation in clinical practice.

PMID- 29594024
TI  - Can active surveillance really reduce the harms of overdiagnosing prostate
      cancer? A reflection of real life clinical practice in the PRIAS study.
AB  - Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears
      to provide excellent long-term PCa-specific and overall survival. The choice for
      AS as initial treatment is mainly based on avoiding side effects from invasive
      treatment; but AS entails regular check-ups and the possibility of still having
      to switch or deciding to switch to invasive treatment. Here, we assessed the long
      term follow-up data from AS in real life clinical practices. Methods: Data from
      the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8
      countries, were analyzed to provide long-term follow-up results. Men were advised
      to be regularly examined with prostate-specific antigen (PSA) tests, digital
      rectal examinations, and prostate biopsies. Men were advised to switch to
      invasive treatment if they had disease reclassification [Gleason score (GS) >=3+4
      on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA
      doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for
      discontinuing AS, and rates of potential unnecessary biopsies and treatments.
      Results: The median follow-up time was 6.5 years. During this period, 325 (65%)
      men discontinued after a median of 2.3 years and 121 (24%) men had no recent (>1
      year) data-update after a median of 7.3 years. The remaining 54 (11%) men were
      confirmed to be still on AS. Most men discontinued based on protocol advice; 38%
      had other reasons. During follow-up, 838 biopsy sessions were performed of which
      79% to 90% did not lead to reclassification, depending on the criteria. Of the
      325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126
      underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had
      another or unknown treatment. RP results were available of 99 men: 34% to 68%,
      depending on definition, had favorable outcomes; 50% of unfavorable the outcomes
      occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to
      PCa. Conclusions: These data, reflecting real life clinical practice, show that
      more than half of men switched to invasive treatment within 2.3 years, indicating
      limitations to the extent in which AS is able to reduce the adverse effects of
      overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be
      uncoupled from treatment, it remains important to avoid overdiagnosing PCa as
      much as possible.

PMID- 29594025
TI  - Active surveillance: a review of risk-based, dynamic monitoring.
AB  - Active surveillance (AS) is an important treatment modality aiming to reduce the
      overtreatment of patients with prostate cancer (PCa) who have a low risk of
      disease reclassification. After enrolling in AS patients are actively monitored
      using different diagnostic tests (e.g., prostate specific-antigen, digital rectal
      exams (DREs), medical imaging, and prostate biopsies). Biopsy is the most
      burdensome test. We aimed to review schedules for monitoring men on AS. We
      compare fixed versus risk based dynamic monitoring, where biopsies are scheduled
      during follow-up based on dynamic risk predictions. Several prediction models and
      scheduling techniques have been published. All proposed risk prediction models
      need further external validation. We conclude that risk based, dynamic monitoring
      is a promising new strategy to further reduce overtreatment in PCa patients.

PMID- 29594026
TI  - Magnetic resonance imaging in active surveillance-a modern approach.
AB  - In recent years, active surveillance has been increasingly adopted as a
      conservative management approach to low and sometimes intermediate risk prostate
      cancer, to avoid or delay treatment until there is evidence of higher risk
      disease. A number of studies have investigated the role of multiparametric
      magnetic resonance imaging (mpMRI) in this setting. MpMRI refers to the use of
      multiple MRI sequences (T2-weighted anatomical and functional imaging which can
      include diffusion-weighted imaging, dynamic contrast enhanced imaging,
      spectroscopy). Each of the parameters investigates different aspects of the
      prostate gland (anatomy, cellularity, vascularity, etc.). In addition to a
      qualitative assessment, the radiologist can also extrapolate quantitative imaging
      biomarkers from these sequences, for example the apparent diffusion coefficient
      from diffusion-weighted imaging. There are many different types of articles
      (e.g., reviews, commentaries, consensus meetings, etc.) that address the use of
      mpMRI in men on active surveillance for prostate cancer. In this paper, we
      compare original articles that investigate the role of the different mpMRI
      sequences in men on active surveillance for prostate cancer, in order to discuss
      the relative utility of the different sequences, and combinations of sequences.
      We searched MEDLINE/PubMed for manuscripts published from inception to 1st
      December 2017. The search terms used were (prostate cancer or prostate
      adenocarcinoma or prostatic carcinoma or prostate carcinoma or prostatic
      adenocarcinoma) and (MRI or NMR or magnetic resonance imaging or mpMRI or
      multiparametric MRI) and active surveillance. Overall, 425 publications were
      found. All abstracts were reviewed to identify papers with original data. Twenty
      five papers were analysed and summarised. Some papers based their analysis only
      on one mpMRI sequence, while others assessed two or more. The evidence from this
      review suggests that qualitative assessments and quantitative data from different
      mpMRI sequences hold promise in the management of men on active surveillance for
      prostate cancer. Both qualitative and quantitative approaches should be
      considered when assessing mpMRI of the prostate. There is a need for robust
      studies assessing the relative utility of different combinations of sequences in
      a systematic manner to determine the most efficient use of mpMRI in men on active
      surveillance.

PMID- 29594027
TI  - Reduction of MRI-targeted biopsies in men with low-risk prostate cancer on active
      surveillance by stratifying to PI-RADS and PSA-density, with different thresholds
      for significant disease.
AB  - Background: The fear of undergrading prostate cancer (PCa) in men on active
      surveillance (AS) have led to strict criteria for monitoring, which have resulted
      in good long-term cancer-specific survival, proving the safety of this approach.
      Reducing undergrading, MRI-targeted biopsies are increasingly used in men with
      low-risk disease despite their undefined role yet. The objective of this study is
      to investigate the rate of upgrading using MRI-targeted biopsies in men with low
      risk disease on AS, stratified on the basis of PI-RADS and PSA-density, with the
      aim to reduce potential unnecessary repeat biopsy procedures. Methods: A total of
      331 men were prospectively enrolled following the MRI-PRIAS protocol. MR imaging
      was according to Prostate Imaging Reporting and Data System (PI-RADSv2)
      guidelines. Suspicious MRI lesions (PI-RADS 3-5) were additionally targeted by
      MRI-TRUS fusion biopsies. Outcome measure was upgrading to Gleason score (GS)
      >=3+4 with MRI-targeted biopsies, stratified for PI-RADS and PSA-density.
      Results: In total, 25% (82/331) of men on AS showed upgrading from GS 3+3. Only
      3% (11/331) was upgraded to GS >=8. In 60% (198/331) a suspicious MRI lesion was
      identified, but in only 41% (82/198) of men upgrading was confirmed. PI-RADS 3, 4
      and 5 categorized index lesions, showed upgrading in 30%, 34% and 66% of men,
      respectively. Stratification to PI-RADS 4-5, instead of PI-RADS 3-5, would have
      missed a small number of high volume Gleason 4 PCa in PI-RADS 3 category.
      However, further stratification into PI-RADS 3 lesions and PSA-density <0.15
      ng/mL2 could result in a safe targeted biopsy reduction of 36% in this category,
      without missing any upgrades. Conclusions: Stratification with the combination of
      PI-RADS and PSA-density may reduce unnecessary additional MRI biopsy testing.
      Overall, the high rate of detected upgrading in men on AS may result in an
      unintended tightening of continuing in AS. Since patients, included under current
      AS criteria showed extremely favorable outcome, there might be no need to further
      restrict continuing on AS with MRI and targeted biopsies.

PMID- 29594028
TI  - On cribriform prostate cancer.
AB  - The management of newly diagnosed prostate cancer is challenging because of its
      heterogeneity in histology, genetics and clinical outcome. The clinical outcome
      of patients with Gleason score 7 prostate cancer varies greatly. Improving risk
      assessment in this group is of particular interest, as Gleason score 7 prostate
      cancer on biopsy is an important clinical threshold for active treatment.
      Architecturally, four Gleason grade 4 growth patterns are recognized: ill-formed,
      fused, glomeruloid and cribriform. The aim of this review is to describe the role
      of cribriform growth in prostate cancer with respect to diagnosis, prognosis and
      molecular pathology. Secondly, we will discuss clinical applications for
      cribriform prostate cancer and give recommendations for future research.

PMID- 29594029
TI  - Biomarkers in active surveillance.
AB  - The use of active surveillance (AS) is increasing for favorable-risk prostate
      cancer. However, there remain challenges in patient selection for AS, due to the
      limitations of current clinical staging. In addition, monitoring protocols
      relying on serial biopsies is invasive and presents risks such as infection. For
      these reasons, there is substantial interest in identifying markers that can be
      used to improve AS selection and monitoring. In this article, we review the
      evidence on serum, urine and tissue markers in AS.

PMID- 29594030
TI  - Quality of life in active surveillance and the associations with decision-making
      a literature review.
AB  - Several studies have been conducted on the quality of life (QoL) in men with low
      risk prostate cancer (PCa) who choose active surveillance (AS). While recent
      reviews have shown a lack of consistency among the available QoL-studies, a few
      key points have been identified, including decision-making (DM)-related issues
      and their potential effect on QoL. The importance of this theme has also been
      recently highlighted by the international task force of the European School of
      Oncology. However, to our knowledge, there are no studies that have specifically
      marshalled scientific knowledge on the association between DM and QoL among men
      with low-risk PCa undergoing AS. We performed a literature review to fill this
      gap, taking a systematic approach to retrieving and selecting articles that
      included both DM and QoL measures. Among the 272 articles retrieved, we selected
      nine observational, quantitative articles with both DM and QoL measures. The most
      considered DM aspects within these studies were decisional conflict and
      preference for the patient's role in the DM process, as well as health-related
      QoL aspects. The studies included 42 assessments of the relationship between an
      empirical measure of DM and an empirical measure of QoL. Among these assessments,
      23 (55%) were both positive and significant. They mostly concerned the
      relationship between patient-related (decisional self-efficacy, decisional
      control and knowledge) and external (presence of social support, collaborative
      role within the DM process, and influence of different physicians) DM aspects, as
      well as the QoL after choice. The findings of these studies revealed key
      challenges to research and clinical practice related to DM and QoL in AS. These
      include adopting a person-centred perspective where clinicians, caregivers and
      their interactions are also included in evaluations and where the psychosocial
      existential experience of individuals within the DM and AS journey is considered.
      Much more attention needs to be paid to the DM process after diagnosis, as well
      as to all the other moments where patients may have to or want to review their
      decision. Healthcare professionals play a key role in enabling men to make
      informed decisions and to take care of their health and well-being during AS.
      There is still work that needs to be done in training healthcare professionals
      from different disciplines to work together in a model of shared DM and AS
      tailored to the needs of low-risk PCa patients and their family members.

PMID- 29594031
TI  - eHealth and mHealth in prostate cancer detection and active surveillance.
AB  - eHealth and mobile health (mHealth) offer patients, healthcare providers,
      researchers, and policy makers new potential to improve wellness, practice
      prevention and reduce suffering from diseases. While the eHealth market is
      growing to an expected US $26 billion, its potential in the field of Urology is
      still underused. Research has shown that currently only 176 apps (of the 300,000
      medical apps available) were found in the Apple App Store and Google Play Store,
      of which 20 were prostate cancer related. Three good examples of eHealth/mHealth
      applications are the Rotterdam Prostate Cancer Risk Calculator (RPCRC) website
      and app, the Prostate cancer Research International Active Surveillance (PRIAS)
      website and the Follow MyPSA app for men on active surveillance for prostate
      cancer: they are tools with a clear vision that offer true added value in daily
      clinical practice and which positively influence healthcare beyond borders. To
      increase the uptake of eHealth applications in the coming years, it is important
      to involve professionals in their design and development, and to guarantee the
      safety and privacy of its users and their data.

PMID- 29594032
TI  - Being on active surveillance: the patient perspective.
AB  - Prostate cancer (PCa) patients selected for active surveillance (AS) have
      received information on prostate cancer PCa, treatment, knew their serum prostate
      specific antigen (PSA), a digital rectal examination (DRE) done and could rely on
      their set of biopsies to be labelled as low grade, low volume disease (by adding
      a radiographic/ultrasonic measurement). They usually react euphoric to the
      selection hoping to escape invasive curative treatment and its side-effects.
      Unfortunately, this positive feeling waivers in front of uncertainty in the
      follow-up including biopsies. Improvements on prognostics are needed. The
      patients need reassuring information and confidence building to keep his choice
      to AS based on evidence and confidence.

PMID- 29594033
TI  - The future of prostate cancer research: bringing data together, looking back and
      forward.
AB  - The use of digital data in large data sets will be of pivotal importance to
      unravel the biological basis of prostate cancer, and to improve on prevention and
      treatment. For the screening of asymptomatic tumors, their identification, and
      their treatment with better and targeted therapies, the integration of
      information from imaging, genomics, and biomarkers is needed. To bring these
      (un)structured data together, block chain technology is required, while
      knowledgeable analysts should be available. Therefore, it is of utmost importance
      to 'team up' and provide a common strategy for innovation. Its implementation
      needs the involvement of all stakeholders (patients, industries, professionals,
      scientists, governments). This article provides thoughts on how initial steps in
      urology have been taken, and how to proceed.

PMID- 29594034
TI  - Current perspectives on the role of the pharmacist in heart failure management.
AB  - Pharmacists play an important role within a multidisciplinary health care team in
      the care of patients with heart failure (HF). It has been evaluated and
      documented that pharmacists providing medication reconciliation especially during
      transition of care, educating patients on their medications, and providing
      collaborative medication management lead to positive changes in the patient
      outcomes, including but not limited to decreasing in hospitalizations and read
      missions. It is foreseeable that pharmacist roles will continue to expand as new
      treatment and innovative care are developed for HF patients. I reviewed published
      role of pharmacists in the care of HF patients. MEDLINE and Current Content
      database (both from 1966 - December 31, 2017) were utilized to identify peer
      reviewed clinical trials, descriptive studies, and review articles published in
      English using the following search terms: pharmacists, clinical pharmacy, HF, and
      cardiomyopathy. Citations from available articles were also reviewed for
      additional references. Preliminary search revealed 31 studies and 55 reviews.
      They were further reviewed by title and abstract as well as full text to remove
      irrelevant articles. At the end, 24 of these clinical trials and systematic
      reviews are described in the following text and Table 1 summarizes 16 pertinent
      clinical trials. Some roles that are currently being explored include medication
      management in patients with mechanical circulatory support for end-stage HF,
      where pharmacokinetics and pharmacodynamics of medications can change, medication
      management in ambulatory intravenous diuretic clinics, and comprehensive
      medication management in patients' home settings. Pharmacists should continue to
      explore and prospectively evaluate their role in the care of this patient
      population, including documenting their interventions, and impact to economic and
      patient outcomes.

PMID- 29594036
TI  - Dosimetric Impact of a Tumor Treating Fields Device for Glioblastoma Patients
      Undergoing Simultaneous Radiation Therapy.
AB  - Purpose: A recent randomized phase III clinical trial in patients with
      glioblastoma demonstrated the efficacy of tumor treating fields (TTFields), in
      which alternating electric fields are applied via transducer arrays to a
      patient's scalp. This treatment, when added to standard of care therapy, was
      shown to increase overall survival from 16 to 20.9 months. These results have
      generated significant interest in incorporating the use of TTFields during
      postoperative concurrent chemoradiation. However, the dosimetric impact of high
      density electrodes on the scalp, within the radiation field, is unknown. Methods:
      The dosimetric impact of TTFields electrodes in the radiation field was
      quantified in two ways: (1) dose calculated in a treatment planning system and
      (2) physical measurements of surface and deep doses. In the dose calculation
      comparison, a volumetric-modulated-arc-therapy (VMAT) radiation plan was
      developed on a CT scan without electrodes and then recalculated with electrodes.
      For physical measurements, the surface dose underneath TTFields electrodes were
      measured using a parallel plate ionization chamber and compared to measurements
      without electrodes for various incident beam angles and for 12 VMAT arc
      deliveries. Deep dose measurements were conducted for five VMAT plans using
      Scandidos Delta4 diode array: measured doses on two orthogonal diode arrays were
      compared. Results: In the treatment planning system, the presence of the TTFields
      device caused mean reduction of PTV dose of 0.5-1%, and a mean increase in scalp
      dose of 0.5-1 Gy. Physical measurement showed increases of surface dose directly
      underneath by 30-110% for open fields with varying beam angles and by 70-160% for
      VMAT deliveries. Deep dose measurement by diode array showed dose decrease of 1
      2% in most areas shadowed by the electrodes (max decrease 2.54%). Conclusion: The
      skin dose in patients being treating with cranial irradiation for glioblastoma
      may increase substantially (130-260%) with the addition of concurrent TTFields
      electrodes on the scalp. However, the impact of dose attenuation by the
      electrodes on deep dose during VMAT treatment is of much smaller, but
      measureable, magnitude (1-2%). Clinical trials exploring concurrent TTFields with
      cranial irradiation for glioblastoma may utilize scalp-sparing techniques to
      mitigate any potential increase in skin toxicity.

PMID- 29594035
TI  - Targeting Macrophages in Cancer: From Bench to Bedside.
AB  - Macrophages are a major component of the tumor microenvironment and orchestrate
      various aspects of immunity. Within tumors, macrophages can reversibly alter
      their endotype in response to environmental cues, including hypoxia and stimuli
      derived from other immune cells, as well as the extracellular matrix. Depending
      on their activation status, macrophages can exert dual influences on
      tumorigenesis by either antagonizing the cytotoxic activity immune cells or by
      enhancing antitumor responses. In most solid cancers, increased infiltration with
      tumor-associated macrophages (TAMs) has long been associated with poor patient
      prognosis, highlighting their value as potential diagnostic and prognostic
      biomarkers in cancer. A number of macrophage-centered approaches to anticancer
      therapy have been investigated, and include strategies to block their tumor
      promoting activities or exploit their antitumor effector functions. Integrating
      therapeutic strategies to target TAMs to complement conventional therapies has
      yielded promising results in preclinical trials and warrants further
      investigation to determine its translational benefit in human cancer patients. In
      this review, we discuss the molecular mechanisms underlying the pro-tumorigenic
      programming of macrophages and provide a comprehensive update of macrophage
      targeted therapies for the treatment of solid cancers.

PMID- 29594037
TI  - Defining the Role of Solid Stress and Matrix Stiffness in Cancer Cell
      Proliferation and Metastasis.
AB  - Solid tumors are characterized by an abnormal stroma that contributes to the
      development of biomechanical abnormalities in the tumor microenvironment. In
      particular, these abnormalities include an increase in matrix stiffness and an
      accumulation of solid stress in the tumor interior. So far, it is not clearly
      defined whether matrix stiffness and solid stress are strongly related to each
      other or they have distinct roles in tumor progression. Moreover, while the
      effects of stiffness on tumor progression are extensively studied compared to the
      contribution of solid stress, it is important to ascertain the biological
      outcomes of both abnormalities in tumorigenesis and metastasis. In this review,
      we discuss how each of these parameters is evolved during tumor growth and how
      these parameters are influenced by each other. We further review the effects of
      matrix stiffness and solid stress on the proliferative and metastatic potential
      of cancer and stromal cells and summarize the in vitro experimental setups that
      have been designed to study the individual contribution of these parameters.

PMID- 29594038
TI  - Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials
      Loaded with Immunoadjuvants.
AB  - In this study, we investigate the use of multifunctional smart radiotherapy
      biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect
      of local radiotherapy (RT). SRBs were designed similar to currently used inert RT
      biomaterials, incorporating a biodegradable polymer with reservoir for loading
      payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors
      were generated both on the right and left flank of each mouse, with the left
      tumor representing metastasis. The mice were randomized and divided into eight
      cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another
      similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were
      performed using a small animal radiation research platform (SARRP). Tumor volume
      measurements for both flank tumors and animal survival was assessed over 25
      weeks. Tumor volume measurements showed significantly enhanced inhibition in
      growth for the right flank tumors of mice in the cohort treated with SRBs loaded
      with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with
      CD40 mAbs without RT could generate an immune response, consistent with previous
      studies showing such response when using anti-CD40. Overall, 60% of mice treated
      with SRBs showed complete tumor regression during the observation period,
      compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB.
      Complete tumor regression was not observed in any other cohorts. The findings
      justify more studies varying RT doses and quantifying the immune-cell populations
      involved when using SRBs. Such SRBs could be developed to replace currently used
      RT biomaterials, allowing not only for geometric accuracy during RT, but also for
      extending RT to the treatment of metastatic lesions.

PMID- 29594039
TI  - Genetic Evidence for Early Peritoneal Spreading in Pelvic High-Grade Serous
      Cancer.
AB  - Background: Most pelvic high-grade serous (HGS) carcinomas have been proposed to
      arise from tubal primaries that progress rapidly to advanced disease. However,
      the temporal sequence of ovarian and peritoneal metastases is not well
      characterized. Methods: To establish the sequence of metastases, phylogenetic
      relationships among the ovarian and peritoneal carcinomas were determined from
      single-nucleotide variations (SNVs) in nine tumor regions from each patient with
      pelvic HGS carcinomas. Somatic SNVs from each tumor sample were used to
      reconstruct phylogenies of samples from each patient. Variant allele frequencies
      were used to reconstruct subclone phylogenies in each tumor sample. Results: We
      show that pelvic HGS carcinomas are highly heterogeneous, only sharing less than
      4% of somatic SNVs among all nine carcinoma implants in one patient. TP53
      mutations are found in all nine carcinoma implants in each patient. The
      phylogenetic analyses reveal that peritoneal metastases arose from early
      branching events that preceded branching events for ovarian carcinomas in some
      patients. Finally, subclone phylogenies indicate the presence of multiple
      subclones at each tumor implant and early tumor clones in peritoneal implants.
      Conclusion: The genetic evidence that peritoneal implants arose before or
      concurrently with ovarian implants is consistent with the emerging concept of the
      extra-ovarian origin of pelvic HGS cancer. Our results challenge the concept of
      stepwise spatial progression from the fallopian primary to ovarian carcinomas to
      peritoneal dissemination and suggest an alternative progression model where
      peritoneal spreading of early clones occurs before or in parallel with ovarian
      metastases.

PMID- 29594040
TI  - Cancer Cell Mechanics: Adhesion G Protein-coupled Receptors in Action?
AB  - In mammals, numerous organ systems are equipped with adhesion G protein-coupled
      receptors (aGPCRs) to shape cellular processes including migration, adhesion,
      polarity and guidance. All of these cell biological aspects are closely
      associated with tumor cell biology. Consistently, aberrant expression or
      malfunction of aGPCRs has been associated with dysplasia and tumorigenesis.
      Mounting evidence indicates that cancer cells comprise viscoelastic properties
      that are different from that of their non-tumorigenic counterparts, a feature
      that is believed to contribute to the increased motility and invasiveness of
      metastatic cancer cells. This is particularly interesting in light of the recent
      identification of the mechanosensitive facility of aGPCRs. aGPCRs are signified
      by large extracellular domains (ECDs) with adhesive properties, which promote the
      engagement with insoluble ligands. This configuration may enable reliable force
      transmission to the ECDs and may constitute a molecular switch, vital for mechano
      dependent aGPCR signaling. The investigation of aGPCR function in
      mechanosensation is still in its infancy and has been largely restricted to
      physiological contexts. It remains to be elucidated if and how aGPCR function
      affects the mechanoregulation of tumor cells, how this may shape the mechanical
      signature and ultimately determines the pathological features of a cancer cell.
      This article aims to view known aGPCR functions from a biomechanical perspective
      and to delineate how this might impinge on the mechanobiology of cancer cells.

PMID- 29594042
TI  - Biotherapies in Solid Tumors: Are Negative Results Still of Low Priority for
      Publication?
AB  - In 2005, we performed the largest survey on clinical trials of biotherapies for
      all solid tumors and found indirect evidence of a publication bias: editors of
      medical journals were more prone to publish positive results independently from
      the quality of the studies. We collected data from 2003 to 2015 in 487 studies,
      and the publication bias previously described was not found in the years between
      2010 and 2015: this could be related to changes and/or innovations in the
      guidelines and editorial policies of oncology journals occurred over the last
      years.

PMID- 29594041
TI  - DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse
      Intrinsic Pontine Gliomas: A Case Report.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) are aggressive glial brain tumors that
      primarily affect children, for which there is no curative treatment. Median
      overall survival is only one year. Currently, the scientific focus is on
      expanding the knowledge base of the molecular biology of DIPG, and identifying
      effective therapies. Oncolytic adenovirus DNX-2401 is a replication-competent,
      genetically modified virus capable of infecting and killing glioma cells, and
      stimulating an anti-tumor immune response. Clinical trials evaluating
      intratumoral DNX-2401 in adults with recurrent glioblastoma have demonstrated
      that the virus has a favorable safety profile and can prolong survival.
      Subsequently, these results have encouraged the transition of this biologically
      active therapy from adults into the pediatric population. To this aim, we have
      designed a clinical Phase I trial for newly diagnosed pediatric DIPG to
      investigate the feasibility, safety, and preliminary efficacy of delivering DNX
      2401 into tumors within the pons following biopsy. This case report presents a
      pediatric patient enrolled in this ongoing Phase I trial for children and
      adolescents with newly diagnosed DIPG. The case involves an 8-year-old female
      patient with radiologically diagnosed DIPG who underwent stereotactic tumor
      biopsy immediately followed by intratumoral DNX-2401 in the same biopsy track.
      Because there were no safety concerns or new neurological deficits, the patient
      was discharged 3 days after the procedures. To our knowledge, this is the first
      report of intratumoral DNX-2401 for a patient with DIPG in a clinical trial. We
      plan to demonstrate that intratumoral delivery of an oncolytic virus following
      tumor biopsy for pediatric patients with DIPG is a novel and feasible approach
      and that DNX-2401 represents an innovative treatment for the disease.

PMID- 29594043
TI  - In Vitro Model-Systems to Understand the Biology and Clinical Significance of
      Circulating Tumor Cell Clusters.
AB  - The isolation of clusters of circulating tumor cells (CTCs) from cancer patients
      has recently challenged the accepted view that the initiation of secondary tumors
      during metastasis involves the dissemination of individual cancer cells. As such
      clusters appear to be more aggressive than single tumor cells, CTC clusters are
      now considered a main player in the metastatic process, and many studies are
      exploring their diagnostic, prognostic, and clinical significance. However,
      several technical challenges limit advances in this area. Here, we suggest the
      use of established cancer cell lines that grow as cell clusters in suspension as
      a complementary approach that can help in understanding the biology of CTC
      clusters and their clinical significance. We argue that the many similarities
      between these "surrogate" clusters and the CTC clusters isolated from patients
      (e.g., in terms of size, morphology, heterogeneous expression of epithelial and
      mesenchymal markers, and type of cell-cell junctions) make these cell lines ideal
      systems for the development of strategies aimed at preventing or slowing down the
      metastatic process by targeting CTC clusters.

PMID- 29594044
TI  - A Phase Ib/II Study of Ganetespib With Doxorubicin in Advanced Solid Tumors
      Including Relapsed-Refractory Small Cell Lung Cancer.
AB  - Introduction: Small cell lung cancer (SCLC) accounts for 15% of all lung cancers
      and is characterized by high response rates to cytotoxic chemotherapy and equally
      high rates of relapse. Many resistance mechanisms have been proposed including
      resistance to doxorubicin via induction of a heat shock response. Ganetespib is a
      novel and potent non-geldanamycin heat shock protein 90 (Hsp90) inhibitor. In
      preclinical studies, synergy between ganetespib and doxorubicin was shown. We
      conducted a phase Ib/II study of the safety, tolerability, and preliminary
      efficacy of the combination of ganetespib and doxorubicin. Methods: Patients
      eligible for the phase Ib portion had advanced tumors that would be appropriate
      for doxorubicin therapy and those in the phase II portion had relapsed or
      refractory SCLC. All patients had an ECOG performance status, 0-1 and adequate
      organ function, including a cardiac ejection fraction >=50%. Patients who
      received a lifetime cumulative doxorubicin dose of >150 mg/m2 or who had
      symptomatic brain metastases were excluded. Patients received ganetespib on Days
      1 and 8 and doxorubicin 50 mg/m2 on day 1 in 21-day cycles. Results: Eleven
      patients were enrolled including nine in the phase Ib dose escalation and two in
      the phase II expansion. The study was terminated by the sponsor. The dose
      recommended for future study is ganetespib 150 mg/m2 in combination with
      doxorubicin at a dose of 50 mg/m2. The most common adverse events of the
      combination were grade 1/2 diarrhea, nausea, fatigue, and transaminitis. No dose
      limiting toxicities were observed. Response rate was 25% and median duration of
      response was 137 days. Conclusion: Ganetespib plus doxorubicin was a well
      tolerated combination and there remains potential for the clinical development of
      Hsp90 inhibitors in SCLC. Clinical Trial Registration:
      https://ClinicalTrials.gov/ct2/show/NCT02261805, identifier NCT02261805.

PMID- 29594045
TI  - Cumulative Doses to Brain and Other Critical Structures After Multisession Gamma
      Knife Stereotactic Radiosurgery for Treatment of Multiple Metastatic Tumors.
AB  - Purpose: Repeat stereotactic radiosurgery (SRS) is an attractive alternative to
      whole brain radiation therapy (WBRT) for treatment of recurrent brain metastases
      (BM). The purpose of this study is to determine the cumulative doses to the brain
      and critical normal structures in patients who underwent repeat courses of Gamma
      Knife (GK) SRS. Materials and methods: We retrospectively identified ten patients
      who received at least three GK-SRS sessions for multiply recurrent BM at our
      institution from 2013 to 2016. We used VelocityTM 3.1.0 software to co-register
      the magnetic resonance imaging images and the dose data of all treatment sessions
      for each patient. The cumulative doses to brain, lenses, eyes, brainstem, optic
      nerves, chiasm, and hippocampi were calculated. Dose-volume histograms, as well
      as the mean, median and maximum doses of these structures, were analyzed.
      Results: The median number of SRS was five sessions (range = 3-7 sessions) per
      patient over a median treatment span of 510 days (112-1,197 days), whereas the
      median number of metastatic tumors treated per patient was 25.0 (10-63). The
      median of the total tumor volume was 9.5 cc (2.3-75.9 cc). The median of the mean
      cumulative dose to the whole brain was 4.1 Gy (1.7-16.4 Gy). The medians of the
      maximum doses to the critical structures were as follows: brainstem, 6.1 Gy (2.2
      28.9 Gy), chiasm, 3.9 Gy (1.8-10.8 Gy), right optic nerve, 2.9 Gy (1.2-9.0 Gy),
      and left optic nerve, 2.6 Gy (1.0-6.5 Gy). The medians of the mean and maximum
      cumulative doses to the hippocampi were 3.4 Gy (1.0-14.4 Gy) and 13.8 Gy (1.5
      39.3 Gy), respectively. The median survival for the entire cohort was 26.7
      months, and no patients developed radiation necrosis. Conclusion: Our study
      demonstrated that multisession GKSRS could be delivered with low cumulative doses
      to critical normal structures. Further studies are required to fully establish
      its role as an alternative treatment strategy to WBRT for the treatment of
      multiply recurrent BM.

PMID- 29594047
TI  - The 7th Year of Uninterrupted Publication of the European Thyroid Journal.

PMID- 29594046
TI  - A Cartography of Siglecs and Sialyltransferases in Gynecologic Malignancies: Is
      There a Road Towards a Sweet Future?
AB  - Altered surface glycosylation is a key feature of cancers, including gynecologic
      malignancies. Hypersialylation, the overexpression of sialic acid, is known to
      promote tumor progression and to dampen antitumor responses by mechanisms that
      also involve sialic acid binding immunoglobulin-like lectins (Siglecs),
      inhibitory immune receptors. Here, we discuss the expression patterns of Siglecs
      and sialyltransferases (STs) in gynecologic cancers, including breast, ovarian,
      and uterine malignancies, based on evidence from The Cancer Genome Atlas. The
      balance between sialosides generated by specific STs within the tumor
      microenvironment and Siglecs on leukocytes may play a decisive role for antitumor
      immunity. An interdisciplinary effort is required to decipher the characteristics
      and biological impact of the altered tumor sialome in gynecologic cancers and to
      exploit this knowledge to the clinical benefit of patients.

PMID- 29594048
TI  - In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice.
AB  - Objectives: Thyronamines are decarboxylated and deiodinated metabolites of
      thyroid hormones (THs). Of all possible thyronamine variants, only 3
      iodothyronamine (3-T1AM) and iodine-free thyronamine (T0AM) have been detected in
      vivo. While intensive research has been done on the (patho-)physiological action
      of 3-T1AM, the role of T0AM has been studied less intensively. Study Design: We
      determined whether a single pharmacological dose (50 mg/kg, i.p.) or repeated
      administration (5 mg/kg/day, i.p., for 7 days) of T0AM affects metabolism,
      cardiovascular function, or thermoregulation in male C57BL/6J mice. Since
      selenium (Se) is important for proper TH function and Se metabolism is affected
      by TH, we additionally analyzed Se concentrations in liver, serum, and kidney
      using total reflection X-ray analysis. Results: A single injection of T0AM had no
      effect on heart rate, temperature, or activity as assessed by radio telemetry.
      Likewise, daily administration of T0AM did not alter body weight, food or water
      intake, heart rate, blood pressure, brown adipose tissue thermogenesis, or body
      temperature, and no significant differences in hepatic glycogen content or mRNA
      expression of genes involved in cardiovascular function or metabolic control were
      determined. Also, the X-ray analysis of Se concentrations revealed no significant
      changes. However, hepatic T0AM was significantly increased in the treated
      animals. Conclusions: In summary, our data demonstrate that T0AM elicits no
      obvious metabolic, cardiovascular, or thermoregulatory activities in mice. As
      T0AM does also not interfere with TH or Se metabolism, we conclude that the
      deiodination of 3-T1AM to T0AM constitutes an efficient inactivation mechanism,
      terminating the actions of the more powerful precursor.

PMID- 29594049
TI  - Positron Emission Tomography (PET) and PET/CT in Thyroid Cancer: A Systematic
      Review and Meta-Analysis.
AB  - Background: Positron emission tomography (PET) and PET/CT are functional imaging
      methods that are widely used in diagnostic procedures in oncology. Objectives:
      The objective of this study was to assess the patient-relevant benefit of PET or
      PET/CT in patients with thyroid cancer based on a literature review and meta
      analysis. Methods: A systematic review including studies that had been published
      until December 2013 was performed. To be included, studies had to prospectively
      investigate patients with thyroid cancer in a clinical setting of staging,
      restaging, or diagnosing tumour recurrence. Results: Out of 3,506 potentially
      relevant articles, 29 studies were included. No study directly evaluated the
      benefits of PET. Twenty-eight studies dealt with the diagnostic accuracy of PET
      or PET/CT, and 1 study evaluated the prognostic value of PET/CT. The authors
      showed that a positive result of PET/CT in restaging patients with differentiated
      thyroid cancer yielded a significant decrease in overall survival (hazard ratio,
      HR 5.01, CI 3.41-6.62). In patients with suspected recurrence of differentiated
      thyroid cancer, meta-analysis showed higher sensitivity of PET (89.7%, CI 78-99%)
      and PET/CT (94.3%, CI 87-97%) compared with conventional imaging (65.4%, CI 32
      88%) and comparable results for specificity. Due to the low numbers of studies
      and patients, meta-analyses on medullary carcinoma did not produce meaningful
      results. Conclusion: The patient-relevant benefits of PET or PET/CT in thyroid
      cancer could not be evaluated satisfactorily based on the included studies. It
      remains unclear whether higher diagnostic test accuracy leads to changes in
      therapeutic strategies and better patient-relevant outcomes.

PMID- 29594050
TI  - Ultrasound Measurements of Thyroid Gland Volume at 36 Weeks' Corrected
      Gestational Age in Extremely Preterm Infants Born before 28 Weeks' Gestation.
AB  - Background: Thyroid ultrasound is a non-invasive imaging tool and provides good
      evaluation of thyroid anatomy, location, vascularisation, and echogenicity. The
      aim of this study was to assess thyroid function and thyroid volume in extremely
      preterm infants born before 28 weeks' gestation evaluated at 36 weeks' corrected
      gestational age (CGA) compared to term infants' normative data in the literature.
      Design: In this largest prospective UK study of extremely premature infants born
      at less than 28 weeks' gestation, thyroid volume measurement was assessed at 36
      weeks' CGA. Fifty-five extremely preterm infants (28 males) who were born before
      28 weeks' gestation were recruited to the study. All infants had ultrasound
      assessment of the thyroid gland at 36 weeks' CGA. We also prospectively measured
      thyroid stimulating hormone (TSH) and free thyroxine (FT4) in all infants at the
      time of recruitment (within 5 days of birth), at days 14, 21, and 28, and at 36
      weeks' CGA. Results: The mean thyroid volume was measured at 0.57 mL (SD +/
      0.18). There was no association between mean thyroid volume and thyroid function
      (TSH or FT4). No associations were found between mean thyroid volume and
      gestation or birth weight in these infants. Conclusions: Our findings provide a
      reference range with a mean thyroid volume of 0.57 mL (SD +/-0.18) in this
      extremely preterm age group if less than 28 weeks' gestation. Thyroid volume at
      birth can vary from country to country due to variations in iodine intake as well
      as gestational age.

PMID- 29594051
TI  - Vitamin D in Graves Disease: Levels, Correlation with Laboratory and Clinical
      Parameters, and Genetics.
AB  - Objective: The aim was to compare the vitamin D levels in patients with Graves
      disease (GD) with the general population and to correlate the vitamin D levels
      with laboratory and clinical parameters in GD. Moreover, we examined the genetic
      variation in genes involved in the vitamin D metabolism and their association
      with GD. Methods: The levels of vitamin D were compared in 292 patients with
      newly diagnosed GD and 2,305 controls. Single nucleotide polymorphisms (SNPs) in
      the vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-alpha
      hydroxylase (CYP27B1) were examined for association with GD and/or Graves
      ophthalmopathy (GO) in 708 patients and 1,178 controls. Results: Patients with GD
      had significantly lower vitamin D levels compared to controls (55.0 +/- 23.2 vs.
      87.2 +/- 27.6 nmol/L, p < 0.001). In patients with GD (n = 219), there was no
      association between the levels of vitamin D at diagnosis and free thyroxine
      (fT4), free triiodothyronine (fT3), thyrotropin receptor antibodies (TRAb), GO at
      diagnosis, or relapse after terminating treatment with antithyroid drugs. Two
      SNPs in VDR were associated with GD: rs10735810 (OR = 1.36, 95% CI: 1.02-1.36, p
      = 0.02) and rs1544410 (OR = 1.47, 95% CI: 1.03-1.47, p = 0.02). There was no
      difference in the mean vitamin D level between genotypes in either rs10735810 or
      rs154410. Conclusions: Patients with GD had lower vitamin D levels compared to
      the general population; however, the vitamin D levels did not affect the
      laboratory or clinical parameters of GD. SNPs in the VDR influenced the risk of
      GD through mechanisms other than reducing the vitamin D levels.

PMID- 29594052
TI  - Parathyroid Hormone Assays following Total Thyroidectomy: Is There a Predictive
      Value?
AB  - Objectives: Parathyroid hormone (PTH) is a risk marker for hypoparathyroidism
      (hypoPTH). This study aimed to determine the predictive values of early PTH
      assays carried out at the moment of skin closure (PTH SC), to establish a
      treatment algorithm, identifying two threshold values. We assessed the
      reproducibility of this approach with two different immunoassay kits (hypoPTH)
      after total thyroidectomy, but its practical application is not consensual. Study
      Design: We conducted a prospective descriptive study, including all patients who
      underwent a total thyroidectomy between March 2012 and November 2013.
      Postoperative PTH SC levels, corrected calcium on postoperative days, and
      occurrence of hypoPTH symptoms were collected. Results: Of 257 patients, the rate
      of hypoPTH was 20%. Threshold values to obtain a 100% positive predictive value
      to identify patients for whom hypoPTH was absolutely certain were: PTH SC <7 ng/L
      for the Roche kit and PTH SC <4 ng/L for the Beckman-Coulter kit. Threshold
      values to obtain a 100% negative predictive value to identify patients for whom
      the absence of hypoPTH was absolutely certain were: PTH SC >=19 ng/L for the
      Roche kit and PTH SC >=9 ng/L the Beckman-Coulter kit. Conclusions: A single
      serum PTH sampled at skin closure is a reliable test to predict hypoPTH after a
      total thyroidectomy. The use of a threshold based on a 100% negative predictive
      value enables patients with no risk of hypoPTH to be safely discharged within the
      first 24 h postoperatively without unnecessary calcium and vitamin treatment.
      This medication can be given promptly to patients at risk of hypoPTH to limit the
      occurrence of hypocalcaemia.

PMID- 29594053
TI  - Indeterminate Thyroid Nodules: A Pragmatic Approach.
AB  - Background: Fine needle aspiration (FNA) cytology fails to provide a conclusive
      diagnosis in a subset of thyroid lesions labeled as "indeterminate" (Thy3). In
      this study, we aimed at ascertaining the prevalence of Thy3 thyroid nodules in a
      hitherto unreported ethnic group (residents of the United Arab Emirates).
      Methods: We retrospectively examined 688 FNA of the thyroid performed on 584
      patients. Samples were reported using the Royal College of Physicians' (RCP) Thy
      classification. The results of the FNA were correlated with the final surgical
      specimens. Ultrasonography (US) risk stratification was calculated using a web
      based US risk of malignancy calculator. Results: Overall sample adequacy was 97%.
      The indeterminate group Thy3 was found in 7% of the samples. The overall risk of
      malignancy in the Thy3 category was 20%. This risk was very similar in the 2
      subgroups of Thy3 (17% in Thy 3a and 22% in Thy3f). Subdividing the Thy3 group
      into subgroups becomes less necessary if the US scoring is <24.5% since the
      negative predictive value, in this case, is 100%. Applying this criterion to our
      population would have had the potential of reducing the percentage of patients
      referred to surgery from 61 to 43%. Conclusions: Proper risk stratification of
      Thy3 lesions should be based on the combined risk assessment of clinical,
      cytological, radiological, and molecular data. Such a pragmatic approach is
      expected to reduce the percentage of inappropriate referrals to surgery.

PMID- 29594054
TI  - A Case Report of Syndromic Multinodular Goitre in Adolescence: Exploring the
      Phenotype Overlap between Cowden and DICER1 Syndromes.
AB  - Background: Hereditary tumour predisposition syndromes may increase the risk for
      development of thyroid nodules at a young age. We present the case of an
      adolescent female with Cowden syndrome who had some atypical phenotypic features
      which overlapped with the DICER1 syndrome. Material and Methods: A 17-year-old
      female presented with a 3-month history of progressive right neck swelling. Fine
      needle cytology of the thyroid revealed a follicular neoplasm with features
      suggestive of follicular variant of papillary thyroid carcinoma and she underwent
      a hemithyroidectomy. Enlarging nodules in the remaining thyroid led to a
      completion thyroidectomy at 19 years of age. The patient's past medical history
      included an ovarian mixed malignant germ cell tumour, pulmonary nodules and
      cysts, renal cysts, mucocutaneous lesions, an arachnoid cyst, and a fibrous
      breast lesion. Macrocephaly was noted on physical examination. Results: Based on
      the patient's complex phenotype and young age, a hereditary predisposition
      syndrome was suspected and genetic testing of PTEN and DICER1 was undertaken. A
      heterozygous truncating germ-line PTEN mutation was identified, which combined
      with clinical findings, met criteria for the diagnosis of Cowden syndrome.
      Additional loss of heterozygosity of the wild-type PTEN allele was detected in
      the right thyroid lesion and ovarian tumour. No DICER1 mutations were identified.
      Conclusions: Genetic testing was crucial in elucidating this patient's
      predisposition to the early development of neoplastic and non-neoplastic
      conditions. Our report also highlights the phenotypic overlap between the Cowden
      and DICER1 syndromes and illustrates the importance of recognising the variable
      phenotypic features of hereditary syndromes in order to enable timely
      implementation of appropriate care.

PMID- 29594055
TI  - Occurrence of Graves' Orbitopathy and Graves' Hyperthyroidism after a Trauma to
      the Eye.
AB  - Background: Graves' orbitopathy (GO) is believed to be the consequence of
      autoimmunity against antigens that are present both in the thyroid and orbital
      tissues. Massive release of thyroid antigens causes the appearance or
      deterioration of GO in patients with Graves' hyperthyroidism (GH), as it occurs
      following radioiodine treatment. In theory, a similar release of autoantigens may
      occur at the eye level, for example due to an orbital trauma or surgical
      manipulation. To our knowledge, this is the first report of a case of de novo
      appearance of GO and then GH after an eye trauma, possibly reflecting spreading
      of autoantigens and activation of the immune system against shared orbital and
      thyroid antigens. Case Report: An otherwise healthy, 57-year-old man presented 6
      months after the appearance of a monolateral right orbitopathy, which occurred 40
      days after a trauma in the ipsilateral eye. His thyroid function was normal, with
      positive serum anti-TSH receptor autoantibodies. The thyroid was normal on
      ultrasound. A month later he developed hyperthyroidism and orbitopathy in the
      left eye. Discussion: The development of GO after an eye trauma may reflect
      tissue damage with release of autoantigens and consequent autoimmunity in a
      predisposed individual (our patient had a familial history of autoimmune thyroid
      disease). The subsequent development of hyperthyroidism is in keeping with the
      hypothesis that GH and GO are due to autoimmunity against antigens present both
      in the thyroid and in orbital tissues.

PMID- 29594056
TI  - 2018 European Thyroid Association (ETA) Guidelines for the Management of
      Amiodarone-Associated Thyroid Dysfunction.
AB  - Treatment with amiodarone is associated with changes in thyroid function tests,
      but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and
      amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in
      apparently normal thyroid glands or in the presence of underlying thyroid
      abnormalities. AIH does not require amiodarone withdrawal, and is treated with
      levothyroxine replacement if overt, whereas subclinical forms may be followed
      without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a
      form of iodine-induced hyperthyroidism occurring in nodular goitres or latent
      Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in
      a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic
      mechanisms. AIT 1 is best treated with thionamides that may be combined for a few
      weeks with sodium perchlorate to make the thyroid gland more sensitive to
      thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has
      been restored, AIT 2 patients are followed up without treatment, whereas AIT 1
      patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite
      forms of AIT are treated with thionamides. Oral glucocorticoids can be added from
      the beginning if a precise diagnosis is uncertain, or after a few weeks if
      response to thionamides alone is poor. The decision to continue or to stop
      amiodarone in AIT should be individualized in relation to cardiovascular risk
      stratification and taken jointly by specialist cardiologists and
      endocrinologists. In the presence of rapidly deteriorating cardiac conditions,
      emergency thyroidectomy may be required for all forms of AIT.

PMID- 29594057
TI  - Thyroid Cancer Induction: Nitrates as Independent Risk Factors or Risk Modulators
      after Radiation Exposure, with a Focus on the Chernobyl Accident.
AB  - In recent decades, differentiated thyroid cancer (DTC) incidence has been
      increasing worldwide. The important contributions to this phenomenon of
      "overdiagnosis" driven by wider use of improved ultrasound systems are amply
      documented, notwithstanding the "real" carcinogenic effects of ionizing
      radiation, e.g., from the Chernobyl accident or health care interventions. Less
      well understood is the role of nitrates - as environmental pollutants, in diet,
      and in medication - in thyroid carcinogenesis. Increasing exposure to nitrates is
      associated with rising incidence of esophageal, stomach, bladder, and colon
      cancers. Recent data suggest that in agricultural areas with higher mean nitrate
      levels in groundwater, DTC risk is also elevated. Our work in Belarus after
      Chernobyl has shown that children in districts with high nitrate concentrations
      in drinking water had significantly higher thyroid cancer incidence after
      irradiation than did their counterparts in areas with lower nitrate
      concentrations. Notwithstanding thyroid shielding, increasing use of computed
      tomography and dental X-rays heightens radiation exposure of the salivary glands
      in the general population, especially in children and adolescents. When nitrate
      intake is increased, salivary gland irradiation may potentially result in
      carcinogenic elevations in plasma nitric oxide concentrations. In conclusion,
      excess nitrate intake seems to be an independent risk factor for DTC.
      Additionally, we hypothesize from our data that high nitrate levels modulate the
      carcinogenic effect of radiation on the thyroid. Cohort studies, case-control
      studies, or both, are needed to quantify the effects of nitrates on DTC risk in
      the presence or absence of radiation exposure, e.g., that associated with
      diagnostic or therapeutic health care interventions.

PMID- 29594058
TI  - Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.
AB  - Background: Iodine fortification (IF) may contribute to changes in costs of
      thyroid disease treatment through changes in disease patterns. From a health
      economic perspective, assessment of the development in costs of thyroid disease
      treatment in the population is pertinent. Objectives: To assess the trends in
      annual medicine and hospital costs of thyroid disease treatment during 1995-2015
      in Denmark, i.e., before and after the introduction of mandatory IF in 2000.
      Methods: Information on treatments for thyroid disease (antithyroid medication,
      thyroid hormone therapy, thyroid surgery, and radioiodine treatment) was obtained
      from nationwide registers. Costs were valued at 2015 prices using sales prices
      for medicines and the Danish Diagnosis-Related Group (DRG) and Danish Ambulatory
      Grouping System (DAGS) tariffs of surgeries/radioiodine treatments. Results were
      adjusted for changes in population size and age and sex distribution. Results:
      The total direct medicine and hospital costs of thyroid disease treatment
      increased from EUR ~190,000 per 100,000 persons in 1995 to EUR ~270,000 per
      100,000 persons in 2015. This was mainly due to linearly increased costs of
      thyroid hormone therapy and increased costs of thyroid surgery since 2008. Costs
      of antithyroid medication increased slightly and transiently after IF, while
      costs of radioiodine treatment remained constant. Costs of thyroid hormone
      therapy and thyroid surgery did not follow the development in the prevalence of
      hypothyroidism and structural thyroid diseases observed in concurrent studies.
      Conclusion: The costs of total direct medicine and hospital costs for thyroid
      disease treatment in Denmark increased from 1995 to 2015. This is possibly due to
      several factors, e.g., changes in treatment practices, and the direct effect of
      IF alone remains to be estimated.

PMID- 29594059
TI  - Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab
      Treatment.
AB  - Introduction: Nivolumab is a promising treatment in patients with advanced
      malignancies. Among immune-related adverse events, autoimmune thyroid disorders
      are frequently reported. Patient: A 61-year-old male patient had no history of
      familial or personal thyroid disease. In 2012, this patient, a heavy smoker,
      presented with non-small-cell lung cancer that was treated with radiotherapy and
      chemotherapy. In 2015, the cancer progressed with cervical compressive symptoms,
      and the patient was treated with nivolumab. Results: After 3 infusions, bilateral
      eyelid ptosis and bilateral conjunctival redness with chemosis were observed.
      Ophthalmologic examination revealed severe proptosis with complete
      ophthalmoplegia but with normal vision, color test, and optic disk. Thyroid
      function tests were normal (TSH = 0.65 mU/L, free T4 = 15.4 pmol/L) without anti
      thyroperoxidase or anti-TSH receptor antibodies. CT scan of the orbits confirmed
      marked bilateral proptosis with expansion of the orbital adipose tissue without
      significant thickening of extraocular muscles. T2-weighted MRI showed
      inflammation of orbital adipose tissue. Nivolumab treatment was withdrawn, and
      the patient received weekly intravenous high-dose methylprednisolone (1 g for 2
      weeks, 500 mg for 4 weeks, and 250 mg for 5 weeks). After the first 3 cycles,
      significant improvement of left chemosis was observed whereas bilateral ptosis
      and ophthalmoplegia were unchanged. The patient was euthyroid without thyroid
      autoimmunity 1 week prior to his death due to massive hemoptysis. Conclusion: We
      report severe inflammatory ophthalmopathy in a euthyroid patient with non-small
      cell lung cancer during nivolumab therapy. The occurrence of such ophthalmic
      adverse events is likely to increase during nivolumab therapy in patients with
      advanced malignancies.

PMID- 29594060
TI  - Prevalence of Radiological Signs of Dysthyroid Optic Neuropathy in Magnetic
      Resonance Imaging in Patients with Active, Moderate-to-Severe, and Very Severe
      Graves Orbitopathy.
AB  - Background: Differentiating between dysthyroid optic neuropathy (DON), which
      requires urgent therapy to prevent blindness, and moderate-to-severe Graves
      orbitopathy (GO) remains challenging. There is no pathognomonic feature of DON in
      either ophthalmological or radiological examinations. Objectives: Our aim was to
      investigate the prevalence of radiological signs of DON in magnetic resonance
      imaging (MRI) in patients with moderate-to-severe and very severe GO. Methods:
      Two researchers reassessed MRI scans of 23 consecutive patients (46 eyes) with
      active, moderate-to-severe GO and 14 patients (23 eyes) with very severe GO.
      Typical signs of DON in MRI include apical crowding and optic nerve stretching.
      These were evaluated in the eyes of both groups of patients. Lack of
      cerebrospinal fluid in the optic nerve sheath as well as muscle index values were
      also studied. These clinical evaluations and laboratory results were then
      compared between groups. Results: At least one of the typical radiological
      features of DON was found in 22 (96%) and 16 (35%) eyes with very severe and
      moderate-to-severe GO, respectively. Each occurred statistically more often in
      patients with very severe GO. There were no ophthalmological signs of very severe
      GO observed in the group of patients with moderate-to-severe GO during the study
      or its subsequent follow-up (234 weeks). Conclusions: MRI is a useful tool in
      evaluating very severe GO. However, features typical for DON are also found in up
      to 35% of eyes in patients with active, moderate-to-severe GO. Therefore,
      ophthalmological evaluation seems to be most important in the recognition of very
      severe GO.

PMID- 29594061
TI  - Effects of Chronic Lymphocytic Thyroiditis on the Clinicopathological Features of
      Papillary Thyroid Cancer.
AB  - Background: The effects of chronic lymphocytic thyroiditis (CLT) on the
      presentation and outcome of papillary thyroid carcinoma (PTC) have long been a
      topic of controversy. Objective: To evaluate the effect of coexistent CLT on the
      clinicopathological features of PTC. Design: Retrospective study. Patients: All
      patients with PTC who had been followed by the 2 co-investigators (Juan Rivera
      and Richard J. Payne) between 2006 and 2011 were included. Results: CLT was
      present in 35% (166) of the included patients and was associated with a higher
      proportion of patients with TNM stage I (p = 0.027) and fewer patients with
      persistent disease (p = 0.014) in comparison with the PTC-only group. Analysis of
      the data based on age (<45 or >45 years) revealed that in the older group, the
      presence of CLT was associated with fewer patients with persistent disease (p =
      0.03) and capsular invasion (p = 0.05). However, in patients <45 years of age,
      the presence of CLT was associated with more capsular invasion (p = 0.003) and
      extrathyroidal extension (p = 0.004) compared with the PTC-only group.
      Conclusions: CLT in patients with PTC was associated with lower-stage disease and
      less disease persistence in patients >45 years of age. In patients <45 years, the
      presence of CLT appeared to be associated with unfavorable pathological features.

PMID- 29594062
TI  - Liposarcoma of the Thyroid: A Case Report with a Review of the Literature.
AB  - Background: Liposarcomas of the thyroid gland are extremely rare tumors, and, to
      our knowledge, only 12 cases have been reported in the English literature. An
      accurate diagnosis is challenging due to the nonspecific clinical presentation of
      this cancer, frequently defined just by a swelling of the neck. Patient Findings:
      We present an 82-year-old woman with liposarcoma of the thyroid, complaining of a
      fast-growing neck mass. MRI and neck ultrasound showed a large lipomatous mass,
      which corresponded to a cold nodule in the thyroid scan. After performing a total
      thyroidectomy, the diagnosis of a well-differentiated liposarcoma of the thyroid
      gland was made, showing an MDM2 amplification in fluorescence in situ
      hybridization. Since neither a metastasis nor a residual tumor was found, no
      further adjuvant therapy was needed. Results: We searched the literature for
      previous case reports and identified only 12 cases worldwide to form our
      database. A demographic as well as clinical and histopathological analysis was
      made. In most cases, the liposarcoma occurred in patients >60 years of age. All
      histological subtypes, such as well-differentiated and myxoid liposarcomas, and
      pleomorphic and dedifferentiated liposarcomas, were found in the literature. In
      only 38.46% of the cases, an infiltration of the adjacent organs was observed.
      Surgery was the most common treatment chosen. Conclusions: Our review provides
      clinical and histopathological features of a primary liposarcoma of the thyroid
      to enable the identifi-cation of this rare tumor entity and assist in the
      decision-making process regarding therapeutic options and tumor follow-up.

PMID- 29594063
TI  - Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated
      Cellular Immune Responsiveness.
AB  - Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic
      disease with a global distribution affecting over one million people annually.
      Rats are regarded as one of the most significant reservoir hosts of infection for
      human disease, and in the absence of clinical signs of infection, excrete large
      numbers of organisms in their urine. A unique biological equilibrium exists
      between pathogenic leptospires and reservoir hosts of infection, but
      surprisingly, little is known concerning the host's cellular immune response that
      facilitates persistent renal colonization. To address this deficiency, we
      established and applied an immunocompetent inbred rat model of persistent renal
      colonization; leptospires were detected in urine of experimentally infected rats
      by 3 weeks post-infection and remained positive until 8 weeks post-infection.
      However, there was little, if any, evidence of inflammation in colonized renal
      tubules. At 8 weeks post-infection, a robust antibody response was detected
      against lipopolysaccharide and protein outer membrane (OM) components. Purified B
      and T cells derived from the spleen of infected and non-infected rats
      proliferated in response to stimulation with 0.5 MUg of OM fractions of
      Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells,
      compared to 25% in non-infected controls. However, analysis of gene expression
      did not determine which immunoregulatory pathways were activated. Lymphocytes
      purified from the lymph node draining the site of colonization, the renal lymph
      node, also showed an increase in percentage of proliferating B and T cells.
      However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the
      phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T
      cells. These results confirm that the renal lymph node, the local lymphoid organ,
      is a dominant site containing Leptospira reactive CD4+ T cells and highlight the
      need to consider the local, vs. systemic, immune responses during renal
      colonization infection. The use of inbred immunocompetent rats provides a novel
      tool to further elucidate those pathophysiological pathways that facilitate the
      unique biological equilibrium observed in reservoir hosts of leptospirosis.

PMID- 29594065
TI  - Editorial: Pseudomonas and Acinetobacter: From Drug Resistance to Pathogenesis.

PMID- 29594066
TI  - A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the
      Design and Application of Glycopeptidolipid Mutants.
AB  - Little is known about the disease-causing genetic determinants that are used by
      Mycobacterium abscessus, increasingly acknowledged as an important emerging
      pathogen, notably in cystic fibrosis. The presence or absence of surface exposed
      glycopeptidolipids (GPL) conditions the smooth (S) or rough (R) M. abscessus
      subsp. abscessus (M. abscessus) variants, respectively, which are characterized
      by distinct infective programs. However, only a handful of successful gene knock
      out and conditional mutants have been reported in M. abscessus, testifying that
      genetic manipulation of this mycobacterium is difficult. To facilitate gene
      disruption and generation of conditional mutants in M. abscessus, we have
      designed a one-step single cross-over system that allows the rapid and simple
      generation of such mutants. Cloning of as small as 300 bp of the target gene
      allows for efficient homologous recombination to occur without additional
      exogenous recombination-promoting factors. The presence of tdTomato on the
      plasmids allows easily sifting out the large background of mutants spontaneously
      resistant to antibiotics. Using this strategy in the S genetic background and the
      target gene mmpL4a, necessary for GPL synthesis and transport, nearly 100% of red
      fluorescent clones exhibited a rough morphotype and lost GPL on the surface,
      suggesting that most red fluorescent colonies obtained after transformation
      incorporated the plasmid through homologous recombination into the chromosome.
      This system was further exploited to generate another strain with reduced GPL
      levels to explore how the presence of these cell wall-associated glycolipids
      influences M. abscessus hydrophobicity as well as virulence in the zebrafish
      model of infection. This mutant exhibited a more pronounced killing phenotype in
      zebrafish embryos compared to its S progenitor and this effect correlated with
      the production of abscesses in the central nervous system. Overall, these results
      suggest that the near-complete absence of GPL on the bacterial surface is a
      necessary condition for optimal pathogenesis of this mycobacterium. They also
      suggest that GPL content affects hydrophobicity of M. abscessus, potentially
      altering the aerosol transmission, which is of particular importance from an
      epidemiological and clinical perspective.

PMID- 29594067
TI  - Route of Glucose Uptake in the Group a Streptococcus Impacts SLS-Mediated
      Hemolysis and Survival in Human Blood.
AB  - The transport and metabolism of glucose has been shown to have far reaching
      consequences in the transcriptional profile of many bacteria. As glucose is most
      often the preferred carbon source for bacteria, its presence in the environment
      leads to the repression of many alternate carbohydrate pathways, a condition
      known as carbon catabolite repression (CCR). Additionally, the expression of many
      virulence factors is also dependent on the presence of glucose. Despite its
      importance, little is known about the transport routes of glucose in the human
      pathogen Streptococcus pyogenes. Considering that Streptococcus pyogenes is an
      important human pathogen responsible for over 500,000 deaths every year, we
      characterized the routes of glucose transport in an effort to understand its
      importance in GAS pathogenesis. Using a deletion of glucokinase (DeltanagC) to
      block utilization of glucose imported by non-PTS pathways, we determined that of
      the two glucose transport pathways in GAS (PTS and non-PTS), the non-PTS pathway
      played a more significant role in glucose transport. However, the expression of
      both pathways is linked by a currently unknown mechanism, as blocking the non-PTS
      uptake of glucose reduces ptsI (EI) expression. Similar to the effects of the
      deletion of the PTS pathway, lack of the non-PTS pathway also leads to the early
      activity of Streptolysin S. However, this early activity did not adversely or
      favorably affect survival of DeltanagC in whole human blood. In a subcutaneous
      murine infection model, DeltanagC-infected mice showed increased lesion severity
      at the local site of infection; although, lesion size and dissemination from the
      site of infection was similar to wild type. Here, we show that glucose transport
      in GAS is primarily via a non-PTS pathway. The route of glucose transport
      differentially affects the survival of GAS in whole human blood, as well as the
      lesion size at the local site of infection in a murine skin infection model.

PMID- 29594068
TI  - Construction of a New Phage Integration Vector pFIV-Val for Use in Different
      Francisella Species.
AB  - We recently identified and described a putative prophage on the genomic island
      FhaGI-1 located within the genome of Francisella hispaniensis AS02-814 (F.
      tularensis subsp. novicida-like 3523). In this study, we constructed two variants
      of a Francisella phage integration vector, called pFIV1-Val and pFIV2-Val
      (Francisella Integration Vector-tRNAVal-specific), using the attL/R-sites and the
      site-specific integrase (FN3523_1033) of FhaGI-1, a chloramphenicol resistance
      cassette and a sacB gene for counter selection of transformants against the
      vector backbone. We inserted the respective sites and genes into vector pUC57
      Kana to allow for propagation in Escherichia coli. The constructs generated a
      circular episomal form in E. coli which could be used to transform Francisella
      spp. where FIV-Val stably integrated site specifically into the tRNAVal gene of
      the genome, whereas pUC57-Kana is lost due to counter selection. Functionality of
      the new vector was demonstrated by the successfully complementation of a
      Francisella mutant strain. The vectors were stable in vitro and during host-cell
      infection without selective pressure. Thus, the vectors can be applied as a
      further genetic tool in Francisella research, expanding the present genetic tools
      by an integrative element. This new element is suitable to perform long-term
      experiments with different Francisella species.

PMID- 29594069
TI  - Tetrahymena thermophila Predation Enhances Environmental Adaptation of the Carp
      Pathogenic Strain Aeromonas hydrophila NJ-35.
AB  - Persistence of Aeromonas hydrophila in aquatic environments is the principle
      cause of fish hemorrhagic septicemia. Protistan predation has been considered to
      be a strong driving force for the evolution of bacterial defense strategies. In
      this study, we investigated the adaptive traits of A. hydrophila NJ-35, a carp
      pathogenic strain, in response to Tetrahymena thermophila predation. After
      subculturing with Tetrahymena, over 70% of A. hydrophila colonies were small
      colony variants (SCVs). The SCVs displayed enhanced biofilm formation, adhesion,
      fitness, and resistance to bacteriophage infection and oxidative stress as
      compared to the non-Tetrahymena-exposed strains. In contrast, the SCVs exhibited
      decreased intracellular bacterial number in RAW264.7 macrophages and were highly
      attenuated for virulence in zebrafish. Considering the outer membrane proteins
      (OMPs) are directly involved in bacterial interaction with the external
      surroundings, we investigated the roles of OMPs in the antipredator fitness
      behaviors of A. hydrophila. A total of 38 differentially expressed proteins were
      identified in the SCVs by quantitative proteomics. Among them, three lipoproteins
      including SurA, Slp, and LpoB, and a serine/threonine protein kinase (Stpk) were
      evidenced to be associated with environmental adaptation of the SCVs. Also, the
      three lipoproteins were involved in attenuated virulence of SCVs through the
      proinflammatory immune response mediated by TLR2. This study provides an
      important contribution to the understanding of the defensive traits of A.
      hydrophila against protistan predators.

PMID- 29594064
TI  - Metazoan Parasite Vaccines: Present Status and Future Prospects.
AB  - Eukaryotic parasites and pathogens continue to cause some of the most detrimental
      and difficult to treat diseases (or disease states) in both humans and animals,
      while also continuously expanding into non-endemic countries. Combined with the
      ever growing number of reports on drug-resistance and the lack of effective
      treatment programs for many metazoan diseases, the impact that these organisms
      will have on quality of life remain a global challenge. Vaccination as an
      effective prophylactic treatment has been demonstrated for well over 200 years
      for bacterial and viral diseases. From the earliest variolation procedures to the
      cutting edge technologies employed today, many protective preparations have been
      successfully developed for use in both medical and veterinary applications. In
      spite of the successes of these applications in the discovery of subunit vaccines
      against prokaryotic pathogens, not many targets have been successfully developed
      into vaccines directed against metazoan parasites. With the current increase in 
      omics technologies and metadata for eukaryotic parasites, target discovery for
      vaccine development can be expedited. However, a good understanding of the
      host/vector/pathogen interface is needed to understand the underlying biological,
      biochemical and immunological components that will confer a protective response
      in the host animal. Therefore, systems biology is rapidly coming of age in the
      pursuit of effective parasite vaccines. Despite the difficulties, a number of
      approaches have been developed and applied to parasitic helminths and arthropods.
      This review will focus on key aspects of vaccine development that require
      attention in the battle against these metazoan parasites, as well as successes in
      the field of vaccine development for helminthiases and ectoparasites. Lastly, we
      propose future direction of applying successes in pursuit of next generation
      vaccines.

PMID- 29594070
TI  - Autophagy and Ubiquitination in Salmonella Infection and the Related Inflammatory
      Responses.
AB  - Salmonellae are facultative intracellular pathogens that cause globally
      distributed diseases with massive morbidity and mortality in humans and animals.
      In the past decades, numerous studies were focused on host defenses against
      Salmonella infection. Autophagy has been demonstrated to be an important defense
      mechanism to clear intracellular pathogenic organisms, as well as a regulator of
      immune responses. Ubiquitin modification also has multiple effects on the host
      immune system against bacterial infection. It has been indicated that
      ubiquitination plays critical roles in recognition and clearance of some invading
      bacteria by autophagy. Additionally, the ubiquitination of autophagy proteins in
      autophagy flux and inflammation-related substance determines the outcomes of
      infection. However, many intracellular pathogens manipulate the ubiquitination
      system to counteract the host immunity. Salmonellae interfere with host responses
      via the delivery of ~30 effector proteins into cytosol to promote their survival
      and proliferation. Among them, some could link the ubiquitin-proteasome system
      with autophagy during infection and affect the host inflammatory responses. In
      this review, novel findings on the issue of ubiquitination and autophagy
      connection as the mechanisms of host defenses against Salmonella infection and
      the subverted processes are introduced.

PMID- 29594072
TI  - Tonsillar Lymphoma in Children According to Age Group: A Systematic Review.
AB  - Introduction: Lymphoma is a common malignant tumor of the head and neck occurring
      during childhood. Early diagnosis is very important in terms of prognosis in
      patients with tonsillar lymphoma.Our objective was to evaluate the clinical
      manifestations of pediatric tonsillar lymphoma according to different age groups.
      Materials and Methods: A systematic review of available English, Spanish, or
      Portuguese literature from January 1996 to June 2012 was performedin the BIREME,
      Cochrane, IBECS, Lilacs, PubMed/Medline, SCIELO, and Scopus databases, using
      "tonsillar lymphoma" and "children" as keywords. Inclusion criteria were
      pediatric case reports, patients aged up to 18 years, and information on clinical
      features at the time of diagnosis. Results: Out of 87 identified publications, 13
      articles were selected describing 53 patients. Tonsillar asymmetry was the most
      common sign. Snoring is a common sign in patients aged under 5 years; clinical
      lymphadenopathy is frequent among patients aged between 6 and 10 years; and
      dysphagia is a common sign in patients between 11 and 18 years of age. Burkitt's
      lymphoma is the most common form among all ages studied, followed by B-cell
      lymphoma. Conclusion: Clinical manifestations differ according to age group.
      However, tonsillar asymmetry is the most frequent sign regardless of age group.

PMID- 29594071
TI  - Ecological Restoration of Antibiotic-Disturbed Gastrointestinal Microbiota in
      Foregut and Hindgut of Cows.
AB  - Antibiotically disturbed gastrointestinal microbiota needs a long period time to
      be restored to normal, which may cause a series of problems to the host. The
      understanding of restoration of the biased microbiota by antibiotics remains
      largely unknown. Here, we investigated the microbiota shift in foregut (rumen)
      and hindgut (rectum) of lactating cows after antibiotics exposure as well as
      after antibiotics withdrawal with (Microbiota transplantation, MT group) or
      without (Control, CON group) microbiota transplantation. We were able to
      demonstrate that microbiota in both foregut and hindgut significantly changed
      after 3 or 14 days of antibiotics exposure, and the changes persisted over long
      period of time (>18 days) after withdrawing the antibiotics. We further observed
      a faster restoration of microbiota in both foregut and hindgut of MT group than
      CON group, microbiota in foregut was mainly benefited from microbiota
      transplantation by restoring the alpha-diversity as well as within-group
      similarity, while microbiota in hindgut was primarily benefited from microbiota
      transplantation by reestablishing the co-occurrence network (nodes number, edges
      number, density, modularity as well as closeness centrality). These results
      together expanded our understanding of restoration of the biased microbiota by
      antibiotics, and may also be instructive to deal with the delayed microbiota
      restoration at least in cows.

PMID- 29594073
TI  - Enhancing Working Memory Capacity in Persian Cochlear Implanted Children: A
      Clinical Trial Study.
AB  - Introduction: Sensory deprivations such as hearing impairment that affect sensory
      input have a secondary impact on cognitive functions such as working memory (WM).
      WM capacity is an important cognitive component that processes language-related
      activities. Moreover, several studies have shown a deficit in WM in children with
      a cochlear implant (CI). We aimed to assess the performance of children with CIs
      in pre- and post-training sessions and compare their scores on a battery of WM
      tests to investigate the efficacy of a WM training program. Materials and
      Methods: Twenty-five children aged 7-10 years with a CI participated in this
      study. To train their WM, a computer game was used. In order to examine auditory
      WM, a test battery including standardized digit span (forward and backward
      variations), non-word and sentence repetition (subtest of the Test of Language
      Development-Primary) were assessed in pre- and post-training test sessions at
      Shiraz Implant Center. Results: There were statistically significant differences
      between pre- and post-training test scores on all subtests. Test score
      differences were statistically significant for forward digit span (P=0.003),
      backward digit span (P=0.001), non-word repetition (P=0.001), and sentence
      repetition tasks (P=0.003) before and after training sessions. Conclusion:
      Training may enhance WM capacity. With regards to the importance of WM in
      literacy and learning, it seems applying such intervention programs may be
      helpful in the rehabilitation of implanted children.

PMID- 29594074
TI  - Effect of Early Vestibular Rehabilitation on Vertigo and Unsteadiness in Patients
      with Acute and Sub-Acute Head Trauma.
AB  - Introduction: Vestibular rehabilitation is a treatment option for the management
      of vertigo and unsteadiness, which are very common in head trauma patients and
      more challenging in the early months after trauma. This study evaluated the
      effectiveness of a vestibular rehabilitation program in the recovery of acute and
      sub-acute head trauma patients. The goal of this study was evaluation of the
      effect of early vestibular rehabilitation on patients with acute and sub-acute
      head trauma. Materials and Methods: This study was performed in 20 head trauma
      patients with vertigo and unsteadiness. The patients were randomly divided into
      two groups: one group received medical therapy (Betaserc) and the other received
      rehabilitation and medical therapy. An individualized vestibular rehabilitation
      program was designed that was then revised and verified by a joint committee of
      vestibular rehabilitation groups. The effectiveness of interventions was measured
      using the Dizziness Handicap Inventory (DHI) by comparing the results before and
      after therapy. Results: The physical conditions and DHI scores of patients in
      both groups were similar at baseline. After 1 month of rehabilitation, patients
      receiving vestibular rehabilitation and medication showed greater progress than
      patients receiving medication only (P=0.000). Conclusion: Vestibular
      rehabilitation can aid in the recovery from vertigo and increase the stability of
      head trauma patients. Simultaneous treatment with medicine and vestibular
      rehabilitation exercises can result in quicker and better therapeutic effects.

PMID- 29594075
TI  - Islamic Attitudes and Rhinoplasty.
AB  - Introduction: Although the psychological aspects of rhinoplasty have been fully
      investigated in the medical literature, the religiosity of rhinoplasty candidates
      has not been taken into consideration. Materials and Methods: In this cross
      sectional study, the religious attitudes of 157 rhinoplasty candidates were
      compared with those of 74 subjects who had not requested rhinoplasty. A domestic
      validated reliable questionnaire was completed by all subjects to classify them
      with respect to religious attitude. Other factors such as age, sex and economic
      and educational status were also taken into consideration. From the surgeon's
      perspective, subjects were put into three categories: subjects who had a relative
      indication for rhinoplasty (Category.1), subjects with a well-defined nose based
      on accepted standards of facial aesthetic analysis (Category.2) and finally
      subjects with a severely deformed nose, such as deviated nose or nasal cleft lip
      deformity (Category.3). Results: The mean age among subjects was 28.63 +/- 7.05
      years, and the majority were female (87%). The two groups of participants (those
      who did and did not express a desire for rhinoplasty) were analyzed from the
      point view of age, sex, economic and educational status. The economic and
      educational status of the two groups did not differ significantly (P>0.05). The
      religious score showed a significant difference between those who were interested
      in rhinoplasty (122.75+/-23.49) and those were not interested (138.78+/-21.85;
      P<0.001). Conclusion: Religion may affect a patient's decision to undergo
      rhinoplasty surgery, such that persons with a higher religious attitude tend to
      undertake it less often. However, individuals with major nasal deformities tend
      to decide undertake the surgery, irrespective of religious beliefs.

PMID- 29594076
TI  - Translation, Cross-Cultural Adaptation, Validation and Reliability of the
      Northwestern Dysphagia Patient Check Sheet (NDPCS) in Iran.
AB  - Introduction: Speech and language therapists (SLTs) require proper tools to
      detect dysphagia in the early stages. One of these screening tools is the
      Northwestern Dysphagia Patient Check Sheet (NDPCS). However, this tool needs to
      be adapted, validated, and shown to be reliable for the Persian culture. The aim
      of the present study was to report the validity and reliability of the Persian
      NDPCS (P-NDPCS). Materials and Methods: The NDPCS has 28 items and five sections.
      Beaton's guidelines were followed in terms of the translation process. To report
      the content validity index (CVI) and the content validity ratio (CVR), eight SLTs
      experienced in swallowing disorders examined the content and face validities of
      the P-NDPCS in terms of the quality of translation, fluency, understandability,
      and the cultural context. In total, 140 patients with neurogenic and mechanical
      dysphagia were evaluated using the P-NDPCS. Internal consistency reliability was
      investigated using the Kuder-Richardson formula 20. The interclass correlation
      coefficient (ICC) was used for test-retest reliability. Results: The P-NDPCS
      preserved the 28 items and the five categories of the original version. However,
      semantic and food adjustments were applied due to cultural differences. The
      scoring system was changed from safe/unsafe to yes/no for four subsections and to
      normal/abnormal for the oromotor section. Food requirements were also changed.
      The CVR and CVI were both 75%. The P-NDPCS was shown to have good content
      validity. The internal reliability was 0.95, indicating excellent reliability.
      Conclusion: The equivalence between the original version of the NDPCS and the P
      NDPCS was preserved. Our findings indicate that the P-NDPCSis a valid and
      reliable screening tool for the diagnosis of dysphagia in the early phase.

PMID- 29594077
TI  - Results of Type I Tympanoplasty Using Fascia with or without Cartilage
      Reinforcement: 10 Years' Experience.
AB  - Introduction: There remains controversy about the optimal kind of graft to repair
      tympanic membrane. The purpose of this study was to evaluate the anatomical and
      auditory outcomes of type I tympanoplasty using fascia with or without cartilage
      reinforcement. Materials and Methods: This retrospective cohort study was
      conducted from 2005 to 2015. All cases were surgically treated by a single
      surgeon. We excluded cases in which the etiology of chronic otitis media was
      cholesteatoma. According to the use of cartilage reinforcement in the
      posterosuperior part of the graft, patients were divided into two groups, and the
      results of anatomical and auditory evaluation were compared between the two
      groups. The anatomical outcome was grafting success and the auditory outcome was
      improvement of air bone gap (ABG). Results: A total of 320 patients were
      classified in Group A (tympanoplasty with fascia temporalis only) and 346 were in
      Group B (tympanoplasty with cartilage reinforcement). All patients were followed
      for at least 2 years. The overall success rate in the two groups was 91.6% and
      93.4%, respectively (P=0.3). The most common cause of failure in the two groups
      was re-perforation (5.6% and 3.8%, respectively). The improvement of ABG in two
      groups was 18.5 dB and 3.2 dB, respectively. The difference between two groups
      was statistically significant (P<0.001). Conclusion: In patients with dry
      perforation of the tympanic membrane, the anatomical success with tympanoplasty
      with fascia only or with cartilage reinforcement was similar. However, hearing
      improvement in the fascia only group was greater than in the group undergoing
      cartilage reinforcement.

PMID- 29594078
TI  - Malignant Melanoma of the External Auditory Canal: A Rare Entity.
AB  - Introduction: Although malignant melanomas (MM) are common in the head and neck
      region; primary malignant melanoma of the external auditory canal (EAC) is rare.
      Case Report: We present the case of a 50-year-old symptomatic man with a
      malignant melanoma of the external auditory canal, which clinically masqueraded
      as a haemangioma. The patient subsequently developed extensive loco-regional
      metastasis, requiring extensive surgery. We describe the clinical presentation,
      differential diagnosis, both clinical and pathological in terms of other
      pigmented lesions in the external auditory canal, detailed histopathology, and
      literature review. Conclusion: We want to emphasize the importance of immediate
      and adequate biopsy of any pigmented lesion in the head and neck region to rule
      out MM. Also, we emphasize the importance of deep biopsy for proper
      histopathological assessment in addition to distinguishing it from benign
      melanocytic nevi, in order to initiate treatment.

PMID- 29594079
TI  - Sudden Bilateral Sensorineural Hearing Loss Secondary to Cerebral Venous
      Thrombosis.
AB  - Introduction: Sudden sensorineural hearing loss (SSNHL) is an important
      otological emergency. Up to 90% of the cases are idiopathic. Cerebral venous
      thrombosis (CVT) is an extremely rare identifiable cause as it only represents
      0.5% of all strokes. Case Report: In this paper, an unusual case of bilateral
      SSNHL secondary to bilateral CVT with rapid and complete recovery is reported.
      The patient presented with sudden bilateral hearing loss associated with some
      neurological symptoms. Initial computed tomography (CT) venography revealed a CVT
      of bilateral transverse sinuses. The patient was started on an anticoagulant and
      imaging was repeated after five days, revealing the absence of the thrombosis.
      Serial pure tone audiometry (PTA) showed complete recovery of bilateral hearing
      within 10 days. Conclusion: Early detection and intervention may fasten hearing
      recovery and improve the quality of life. The immediate restoration of venous
      blood flow and intracranial pressure may lead to the complete recovery of
      bilateral hearing loss.

PMID- 29594080
TI  - Surgery and Anesthesia Management for Intraoral Synechia: A Case Report.
AB  - Introduction: Intraoral synechia is a rare congenital condition, generally
      associated with other maxillo-facial malformations. We present a neonate with
      congenital intraoral bilateral synechia without any other facial anomalies. Case
      Report: In this paper, we present a 19-day-old male neonate with congenital
      intraoral bilateral synechia without any other facial anomalies. We review the
      literature to discuss the surgical and anesthesia management of this rare
      congenital disease. Conclusion: The disease manifested with a wide spectrum of
      symptoms. Most cases need surgery and airway management. In patients with a low
      risk of bleeding or a compromised airway, it is possible to manage them with face
      mask-inhalation anesthesia and maintain spontaneous breathing.

PMID- 29594081
TI  - Case Report of an open Neck Procedure Complication Associated with Laryngeal Mask
      Airway Use.
AB  - Introduction: The laryngeal mask airway (LMA) is a safe method to establish
      airway control during general anaesthesia. In otolaryngology surgery, the use of
      a LMA is well established in ear surgery; however, the use of a LMA during open
      neck procedures remains controversial. We report a case in which the pharyngeal
      distortion by the LMA cuff resulted in an iatrogenic complication. Case Report: A
      38-year-old female with a background of multiple myeloma was referred to the
      otolaryngology team for an open cervical lymph node biopsy. The patient was in
      remission after a 2 year post chemotherapy treatment, but now presented with a 4
      week history of persistent nodal enlargement. During the elective procedure,
      pharyngeal distortion from the laryngeal airway mask used for airway management
      resulted in an iatrogenic pharyngeal injury. This case is reported to highlight
      the importance of communication between the surgeon and anesthetist about the
      mode of airway management in open neck surgery. Conclusion: Communication between
      the otolaryngologist and anesthetist is pertinent when selecting the method of
      airway management in open neck procedures. A LMA should be used with caution
      during open neck procedures, with the surgeon recognizing the potential for
      pharyngeal distortion.

PMID- 29594082
TI  - Vancomycin-Induced Stevens-Johnson Syndrome in a Boy Under 2 Years Old: An Early
      Diagnosis by Granulysin Rapid Test.
AB  - Stevens-Johnson syndrome (SJS) is a life-threatening disease, which is mainly
      ascribed to drugs, such as sulfonamides and psychoepileptics. In this article, we
      present a pediatric case of vancomycin-induced SJS and an alternative diagnostic
      algorithm. The patient presented with multiple target-like rashes and vesicles
      throughout the whole body after receiving vancomycin. Despite the fact that skin
      biopsy remains the gold standard for diagnosing SJS, the granulysin rapid test by
      immunochromatographic assay is a non-invasive option for children. In this
      article, we describe our use of the Algorithm of Drug causality for Epidermal
      Necrolysis and a modified T-cell activation assay for granzyme B and interferon
      gamma to screen for the culprit drug. Moreover, we applied the granulysin rapid
      test as an early diagnosis method for children with drug-induced SJS.

PMID- 29594083
TI  - Large Parotid Gland Lipoblastoma in a Teenager.
AB  - Background: Lipoblastomas are rare benign neoplasms that arise from fetal white
      fat cells. They are typically found in children under the age of 3 and have been
      reported in the mediastinum, extremities, and infrequently in the head and neck.
      We present a rare case of a lipoblastoma arising from the parotid gland and the
      first known report of a parotid lipoblastoma in a teenager. Case presentation: A
      15-year-old male presented with a painless, slowly enlarging parotid mass and
      left facial swelling. A fine needle aspiration was non-diagnostic and initial MRI
      showed a 3.8 cm * 5.0 cm * 4.0 cm fatty lesion involving the superficial and deep
      lobes of the left parotid gland and masticator space with widening of the stylo
      mandibular tunnel and thinning of the adjacent mandibular condyle. The patient
      was taken to the operating room, and the mass was excised under general
      anesthesia via a transcervical parotid approach with facial nerve monitoring. The
      most superficial aspect of the parotid bed was spared and with upper and lower
      divisions of the facial nerve preserved. The tumor, which primarily involved the
      deep lobe of the parotid, was entirely excised. Final pathology revealed a 5.2 cm
      lipoblastoma. The patient did well post-operatively with full function of the
      facial nerve and 20 months of follow up without evidence of recurrence.
      Conclusion: This is the first reported case of a lipoblastoma of the parotid
      gland in a teenager. Although a rare tumor, it should be considered in the
      differential diagnosis of a parotid mass in this population.

PMID- 29594084
TI  - Transient Antenatal Bartter's Syndrome: A Case Report.
AB  - Antenatal Bartter's syndrome is a rare inherited disorder characterized by fetal
      polyhydramnios and polyuria that is usually detected between 24 and 30 weeks of
      gestation. However, a rare, severe, but transient form of antenatal Bartter's
      syndrome due to an x-linked melanoma-associated antigen D2 (MAGED2) mutation has
      recently been described. This transient type results in the earlier onset of
      severe polyhydramnios and preterm birth, but spontaneously resolves postnatally.
      Here, we present a case of a 29-week gestation male born to a mother with severe
      polyhydramnios, who was subsequently found to have a novel mutation for MAGED2
      not previously reported. This is the first and only case not to be treated with
      indomethacin, yet still resulted in spontaneous resolution of symptoms. Our case
      suggests the need for awareness of and testing for this new mutation in cases of
      severe antenatal polyhydramnios and discusses the perinatal treatment of this
      condition.

PMID- 29594085
TI  - Stress Signals During Sucking Activity Are Associated With Longer Transition Time
      to Full Oral Feeding in Premature Infants.
AB  - Several treatments have been proposed to shorten the time to the attainment of
      full oral feeding (FOF) for premature infants, but there are only a few
      evaluation methods useful in estimating predictors of this period. We
      investigated whether specific items within the disorganized sucking patterns
      described by the Neonatal Oral-Motor Assessment Scale (NOMAS) could estimate the
      time to FOF in preterm infants with feeding difficulty. Preterm infants diagnosed
      with a disorganized sucking pattern in the NOMAS evaluation before 50 weeks of
      postmenstrual age were included. Video recordings of at least 2 min of oral
      feeding were further analyzed retrospectively by two assessors and the premature
      infants who exhibited disorganized sucking patterns (n = 109) were divided into
      three clusters (clusters 2-4). The observational items compatible with
      disorganization in the original NOMAS were divided into three groups: cluster 2
      (disorganized: arrhythmical), cluster 3 (disorganized: arrhythmical + unable to
      sustain), and cluster 4 (disorganized: arrhythmical + incoordination +/- unable
      to sustain) and further divided into incoordination-positive (cluster 4) and
      incoordination-negative groups (clusters 2 and 3). Premature infants in the
      incoordination-positive group (cluster 4, which means stress signals) showed a
      median transition time of 22 days (range: 4-121 days) which was longer than that
      in the incoordination-negative group (median 6 days; range: 1-25 days).
      Univariate linear regression analysis revealed that the presence of
      incoordination among disorganized sucking patterns (NOMAS cluster 4 vs. clusters
      2 and 3), birth weight, total parenteral nutrition (TPN) duration, non-invasive
      positive pressure ventilation duration, the presence of moderate to severe
      bronchopulmonary dysplasia, pulmonary hypertension, sepsis, small for gestational
      age (SGA), and necrotizing enterocolitis are associated with the transition time
      to FOF. In a multivariate linear regression analysis, the variables revealed to
      be associated with the transition time were TPN duration, SGA, and the presence
      of stress signals (incoordination-positive group) among disorganized sucking
      patterns. When selecting premature infants to be treated with swallowing therapy,
      it is reasonable to pay more attention to the incoordination-positive group
      described in the NOMAS, that is, premature infants with stress signals to shorten
      the time to attain FOF.

PMID- 29594086
TI  - The Megameatus, Intact Prepuce Variant of Hypospadias: Use of the Inframeatal
      Vascularized Flap for Surgical Correction.
AB  - Introduction: The megameatus intact prepuce (MIP) variant of hypospadias is a
      rare variant of hypospadias that is diagnosed either early at the time of
      circumcision or later as the foreskin is retracted. The true incidence of the
      anomaly is difficult to determine precisely as some patient never come to medical
      attention but is felt to under 5% of all cases of hypospadias. The purposes of
      this study are to review the embryology and clinical findings of MIP and then, in
      light of a personal experience, present a series of patients evaluated for MIP
      who were treated with a modification of the Mathieu technique. Materials and
      methods: A PubMed search of all articles in the MIP variant of hypospadias was
      carried out followed by an exhaustive review of the literature. The charts of all
      patients evaluated and treated at Boston Children's Hospital by MC between 2007
      and 2017 were reviewed retrospectively. The patients were divided into two
      groups: those who underwent the standard procedure and those who underwent a
      repair using a modification of the Mathieu procedure using an inframeatal flap.
      Results: The embryologic explanation of the MIP variant is not clear but failure
      of the distal, glanular portion of the urethra to tubularize results in spectrum
      of abnormality characterized by a deep glanular groove and an abnormal opening of
      the urethra anywhere from the mid-glans to a subcoronal location. Surgical repair
      is complicated by a wide distal urethra which may be injured if not properly
      identified. Overall good outcomes were noted with one patient experiencing a
      urethra cutaneous fistula in the first group and one patient having a mild glans
      dehiscence in the second. Conclusion: The MIP variant of hypospadias is a rare
      variant of hypospadias that presents as a spectrum of urethral anomaly. Surgical
      repair may not always be necessary but if surgical repair is carried out, the
      Mathieu technique modification may offer better anatomic delineation of the
      urethra and will provide an extra layer of tissue to cover the reconstructed
      urethra. Low complication rates should be expected with adequate functional
      outcome such as a normal urinary stream. In addition, criteria for selecting
      patients for surgical repair are provided.

PMID- 29594089
TI  - The Need for Specialized Pediatric Cardiac Critical Care Training Program in
      Limited Resource Settings.
AB  - Congenital heart disease (CHD) is one of the major global health problems with
      the highest birth prevalence in low- and middle-income countries. In these
      populous countries, basic health services for the children with CHD, including
      surgery, are lacking. Even though surgery is performed, outcome after cardiac
      surgery is influenced by the quality of the postoperative management with a
      reported high morbidity and mortality. Henceforth, there is an urgent need for
      comprehensive interventions to provide high quality cardiac intensive care
      programs to improve the quality of pediatric cardiac surgery services in order to
      address high morbidity and mortality after cardiac surgery. The development and
      training of the health workers in the field of pediatric cardiac intensive care
      program is required. It is imperative to conduct this training prior to actual
      implementation of the program in limited resources settings.

PMID- 29594087
TI  - Loop-Mediated Isothermal Amplification Methods for Diagnosis of Bacterial
      Meningitis.
AB  - The rapid, accurate, and efficient identification of an infectious disease is
      critical to ensure timely clinical treatment and prevention in public health
      settings. In 2015, meningitis caused by Streptococcus pneumoniae, Haemophilus
      influenzae, and Neisseria meningitidis was responsible for 379,200 (range:
      322,700-444,700) deaths. Clinical features alone cannot determine whether
      bacterial meningitis is present; an analysis of cerebrospinal fluid (CSF) is
      essential. Loop-mediated isothermal amplification (LAMP) is a nucleic acid
      amplification method offering an alternative to polymerase chain reaction (PCR).
      LAMP-based assays for detection of three leading bacteria in CSF for diagnosis of
      meningitis have been established. The typing assays using LAMP for detection of
      meningococcal serogroups A, B, C, W, X, and Y as well as H. influenzae serotypes
      a, b, c, d, e, and f were launched. In comparative analysis of the meningitis
      pathogen assays, LAMP assays did not yield false negative results, and the
      detection rate of LAMP assays was superior compared with PCR or conventional
      culture methods. LAMP assays provide accurate and rapid test results to detect
      major bacterial meningitis pathogens. Accumulating evidence suggests that LAMP
      assays have the potential to provide urgently needed diagnostics for bacterial
      meningitis in resource-limited settings of both developed and developing
      countries.

PMID- 29594088
TI  - Nephropathic Cystinosis: Symptoms, Treatment, and Perspectives of a Systemic
      Disease.
AB  - Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by
      mutations in the CTNS gene. Main dysfunction is a defective clearance of cystine
      from lysosomes that leads to accumulation of cystine crystals in every tissue of
      the body. There are three different forms: infantile nephropathic cystinosis,
      which is the most common form, juvenile nephropatic, and non-nephropathic
      cystinosis. Mostly, first symptom in infantile nephropathic cystinosis is renal
      Fanconi syndrome that occurs within the first year of life. Another prominent
      symptom is photophobia due to corneal crystal deposition. Cystine depletion
      therapy with cysteamine delays end-stage renal failure but does not stop
      progression of the disease. A new cysteamine formulation with delayed-release
      simplifies the administration schedule but still does not cure cystinosis. Even
      long-term depletion treatment resulting in bypassing the defective lysosomal
      transporter cannot reverse Fanconi syndrome. A future perspective offering a
      curative therapy may be transplantation of CTNS-carrying stem cells that has
      successfully been performed in mice.

PMID- 29594090
TI  - Assessing Exposures to Magnetic Resonance Imaging's Complex Mixture of Magnetic
      Fields for In Vivo, In Vitro, and Epidemiologic Studies of Health Effects for
      Staff and Patients.
AB  - A complex mixture of electromagnetic fields is used in magnetic resonance imaging
      (MRI): static, low-frequency, and radio frequency magnetic fields. Commonly, the
      static magnetic field ranges from one to three Tesla. The low-frequency field can
      reach several millitesla and with a time derivative of the order of some Tesla
      per second. The radiofrequency (RF) field has a magnitude in the microtesla range
      giving rise to specific absorption rate values of a few Watts per kilogram. Very
      little attention has been paid to the case where there is a combined exposure to
      several different fields at the same time. Some studies have shown genotoxic
      effects in cells after exposure to an MRI scan while others have not demonstrated
      any effects. A typical MRI exam includes muliple imaging sequences of varying
      length and intensity, to produce different types of images. Each sequence is
      designed with a particular purpose in mind, so one sequence can, for example, be
      optimized for clearly showing fat water contrast, while another is optimized for
      high-resolution detail. It is of the utmost importance that future experimental
      studies give a thorough description of the exposure they are using, and not just
      a statement such as "An ordinary MRI sequence was used." Even if the sequence is
      specified, it can differ substantially between manufacturers on, e.g., RF pulse
      height, width, and duty cycle. In the latest SCENIHR opinion, it is stated that
      there is very little information regarding the health effects of occupational
      exposure to MRI fields, and long-term prospective or retrospective cohort studies
      on workers are recommended as a high priority. They also state that MRI is
      increasingly used in pediatric diagnostic imaging, and a cohort study into the
      effects of MRI exposure on children is recommended as a high priority. For the
      exposure assessment in epidemiological studies, there is a clear difference
      between patients and staff and further work is needed on this. Studies that
      explore the possible differences between MRI scan sequences and compare them in
      terms of exposure level are warranted.

PMID- 29594092
TI  - Herpes Zoster in Persons Living with HIV-1 Infection: Viremia and Immunological
      Defects Are Strong Risk Factors in the Era of Combination Antiretroviral Therapy.
AB  - In a cohort of 4,225 persons living with human immunodeficiency virus type 1 (HIV
      1) infection (PLWH) enrolled at a southeastern US clinic, the overall rate of
      incident herpes zoster (HZ) was 101 per 10,000 person-years (PY) between January
      1999 and 2017, which nearly quadruples the rate reported for the general US
      population. In the same cohort, the median age of HZ diagnosis was 39.5 years
      [interquartile range (IQR) 31.5-49.2] in African American (AA) and 39.1 years
      (IQR 34.9-45.2) in European American (EA) PLWH, with the highest incidence seen
      in PLWH who were over 50 years old (144 and 93 per 10,000 PY in AA and EA,
      respectively, P = 0.18), showing no bias between men (100 per 10,000 PY) and
      women (101 per 10,000 PY). In multivariable models that were applicable to 245 HZ
      cases and 3,713 controls, age, nadir CD4+ T-cell (CD4) count, plasma viral load
      (VL), and duration of combination antiretroviral therapy were independent
      correlates of incident HZ (adjusted P <= 0.006 for all). Regardless of other
      factors, viremic PLWH (VL > 50 copies/mL) was at the highest risk of HZ [adjusted
      odds ratio (OR) > 3.0, P < 0.0001]. PLWH with a nadir CD4 count of >=500
      cells/MUL showed a relatively low risk (adjusted OR = 0.48, P = 0.003). By
      contrast, similar risk estimates were observed with three advancing age groups
      (30-39, 40-49, and >=50) when compared with age <30 (adjusted OR = 1.86-2.17, P
      <= 0.010). These findings indicate that efforts for HZ diagnosis and prophylaxis
      should target viremic PLWH who are over 30 years old and with CD4 count <500
      cells/MUL.

PMID- 29594093
TI  - Offline and Online Sexual Risk Behavior among Youth in the Netherlands: Findings
      from "Sex under the Age of 25".
AB  - Sexually developing adolescents and emerging adults face sexual health risks as
      well as potentially negative outcomes of online sexual behaviors. The goal of
      this study was to describe three categories of sexual risk behavior: (1) behavior
      related to STI/HIV, (2) behavior related to unplanned pregnancy, and (3) online
      sexual risk behavior. In addition, we investigated whether these behaviors are
      actually related to negative (health) outcomes. For this purpose, we used data
      from a Dutch probability survey: "Sex under the age of 25." Adolescents and
      emerging adults aged 12 through 24 (8,053 boys and 12,447 girls) completed a
      digital questionnaire, including measures of the risk of STI/HIV and pregnancy,
      online sexual behavior and non-consensual sex. Chi-square tests and logistic
      regressions were used to test for gender and age differences and compute
      associations between risk behavior and negative outcomes. The results showed that
      the risk of unplanned pregnancy is low in the Netherlands. It seems that
      adolescents and emerging adults are less aware of the risk of STI/HIV than of the
      risk of pregnancy. About 11% of the participants had had more than one partner in
      the last 6 months and had not used condoms consistently with their last partner,
      and these participants had a 3.56 times higher likelihood of ever being diagnosed
      with an STI. Although many young people stop using condoms with their partner
      after a while, most of them did not get tested for STIs. More emerging adults
      (aged 18-24) engage in sexting (sending personal nude pictures and sex videos to
      others), but the chance that these images are shared with other people than the
      intended recipient is higher among adolescents (aged 12-17). The results of this
      study can guide professionals working in sex education and sexual health services
      to focus their efforts on the risk behaviors in the Netherlands that deserve most
      attention.

PMID- 29594091
TI  - Big Data's Role in Precision Public Health.
AB  - Precision public health is an emerging practice to more granularly predict and
      understand public health risks and customize treatments for more specific and
      homogeneous subpopulations, often using new data, technologies, and methods. Big
      data is one element that has consistently helped to achieve these goals, through
      its ability to deliver to practitioners a volume and variety of structured or
      unstructured data not previously possible. Big data has enabled more widespread
      and specific research and trials of stratifying and segmenting populations at
      risk for a variety of health problems. Examples of success using big data are
      surveyed in surveillance and signal detection, predicting future risk, targeted
      interventions, and understanding disease. Using novel big data or big data
      approaches has risks that remain to be resolved. The continued growth in volume
      and variety of available data, decreased costs of data capture, and emerging
      computational methods mean big data success will likely be a required pillar of
      precision public health into the future. This review article aims to identify the
      precision public health use cases where big data has added value, identify
      classes of value that big data may bring, and outline the risks inherent in using
      big data in precision public health efforts.

PMID- 29594094
TI  - Navigating Multiple Sources of Healing in the Context of HIV/AIDS and Wide
      Availability of Antiretroviral Treatment: A Qualitative Study of Community
      Participants' Perceptions and Experiences in Rural South Africa.
AB  - Background: South Africa introduced the world's largest antiretroviral treatment
      (ART) program in 2004 and since 2016 the Department of Health implemented a
      universal Treatment as Prevention (TasP) strategy. However, some studies have
      shown that increasing the availability of ART is insufficient for the
      comprehensive treatment of HIV, since many people still use traditional health
      practitioners (THPs) to avoid being identified as HIV positive, and for reasons
      unrelated to HIV/AIDS. This qualitative study explored the factors influencing
      how both HIV-negative and HIV-positive people choose amongst multiple sources of
      healing and how they engage with them, in the context of HIV/AIDS and wide
      availability of ART. Methods: Data were collected as part of a larger TasP trial
      at the Africa Health Research Institute, KwaZulu-Natal. Repeat in-depth
      individual interviews were conducted with 10 participants. Repeat group
      discussions were conducted with 42 participants. Group discussion data were
      triangulated using community walks and photo-voice techniques to give more
      insight into the perceptions of community members. All data were collected over
      18 months. Thematic analysis was used to analyze participants' narratives from
      both individual interviews and group discussions. Findings: In the context of
      HIV/AIDS and wide availability of ART, use of biomedical and traditional healing
      systems seemed to be common in this locality. People used THPs to meet family
      expectations, particularly those of authoritative heads of households such as
      parents or grandparents. Most participants believed that THPs could address
      specific types of illnesses, especially those understood to be spiritually caused
      and which could not be addressed or cured by biomedical practitioners. However,
      it was not easy for participants to separate some spiritually caused illnesses
      from biological illnesses in the context of HIV/AIDS. These data demonstrate that
      in this context, the use of THPs continues regardless of the wide availability of
      ART. To meet the health care needs of those patients requiring a health care
      system which combines biomedical and traditional approaches, collaboration and
      integration of biomedical and traditional health care should be considered.

PMID- 29594095
TI  - One Health-ness Evaluation of Cysticercosis Surveillance Design in Portugal.
AB  - The increasing occurrence of human cysticercosis, a zoonotic neglected disease,
      is challenging the traditional prevention and control paradigm and calling for
      One Health (OH) solutions in industrialized countries. OH solutions for health
      interventions are increasingly being used to capture expected and unexpected
      outcomes across people, animals, and the environment. The Network for Evaluation
      of One Health (NEOH) proposes an evidence-based framework, relying on systems and
      mixed methods approaches to evaluate the One Health-ness. In this case study,
      this tool is used to evaluate the design of the Observatory of Taeniasis and
      Cysticercosis, as an example of intersectorial collaboration for surveillance in
      Portugal. The OH Initiative (drivers and expected outcomes) and its system
      (boundaries, aim, dimensions, actors, and stakeholders) were described. The
      different aspects of this Initiative were scored with values from 0 (=no OH
      approach) to 1 (=perfect OH approach). The OH index was 0.31. Its OH ratio is
      1.98. Overall scores were as follows: OH thinking 0.75; OH planning 0.60; OH
      working 0.60; OH sharing 0.35; OH learning 0.50; and systemic organization 0.50.
      Operational levels of the Initiative are the main strengths, indicating a
      comprehensive multidimensional innovative approach and transdisciplinarity.
      Critical issues in the supporting infrastructure were observed, related to
      communication, learning and organizational gaps in the project, with the
      evaluation being conducted as the project is being designed and implemented. The
      strengths and weaknesses detected may be used to refine the Initiative. This case
      study therefore exemplifies and supports OH assessment also for ongoing projects,
      at design and early implementation stages for guiding and guaranteeing an OH
      oriented perspective.

PMID- 29594096
TI  - Comparison of Health Service Utilization for Febrile Children Before and After
      Introduction of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination
      Therapy in Rural Papua New Guinea.
AB  - Background: In Papua New Guinea (PNG), a malaria treatment policy using rapid
      diagnostic tests (RDTs) plus artemisinin-based combination therapy (ACT) was
      widely introduced to rural communities in 2012. The objectives of the study were
      to evaluate the effect of this RDT/ACT introduction to a rural PNG population on
      health service utilization and to compare factors associated with health service
      utilization before and after the RDT/ACT introduction. Methods: Household surveys
      with structured questionnaires were conducted before and after the introduction
      of RDT/ACT in a catchment area of a health center in East Sepik Province, PNG. We
      interviewed caregivers with children less than 15 years of age and collected data
      on fever episodes in the preceding 2 weeks. Using propensity score matching,
      febrile children before the introduction of RDT/ACT were matched to febrile
      children after the introduction. Then, the adjusted difference in the proportion
      of health service utilization [i.e., the average treatment effect (ATE) of the
      introduction of RDT/ACT on health service utilization] was estimated. We also
      employed a multilevel Poisson regression model to investigate factors influencing
      the use of health services. Results: Of 4,690 children, 911 (19%) were reported
      to have a fever episode. The unadjusted proportion of health service utilization
      was 51.7 and 57.2% before and after the RDT/ACT introduction, respectively. After
      matching, no significant difference in the health service utilization was
      observed before and after the introduction of RDT/ACT (ATE: 0.063, 95% confidence
      interval -0.024 to 0.150). Multilevel regression analysis showed that the
      consistent factors associated with a higher utilization of health services were
      severe illness and being female. Conclusion: The utilization of health services
      was not significantly different before and after the introduction of RDT/ACT.
      Villagers may have neither sufficient informations on the new protocol nor high
      acceptance of RDT/ACT. The observed gender bias in health service utilization
      could be due to female caregivers' preferences toward girls.

PMID- 29594097
TI  - Designing Superoxide-Generating Quantum Dots for Selective Light-Activated
      Nanotherapy.
AB  - The rapid emergence of superbugs, or multi-drug resistant (MDR) organisms, has
      prompted a search for novel antibiotics, beyond traditional small-molecule
      therapies. Nanotherapeutics are being investigated as alternatives, and recently
      superoxide-generating quantum dots (QDs) have been shown as important candidates
      for selective light-activated therapy, while also potentiating existing
      antibiotics against MDR superbugs. Their therapeutic action is selective, can be
      tailored by simply changing their quantum-confined conduction-valence band (CB
      VB) positions and alignment with different redox half-reactions-and hence their
      ability to generate specific radical species in biological media. Here, we show
      the design of superoxide-generating QDs using optimal QD material and size well
      matched to superoxide redox potential, charged ligands to modulate their uptake
      in cells and selective redox interventions, and core/shell structures to improve
      their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs
      with conduction band (CB) position at -0.5 V with respect to Normal Hydrogen
      Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective
      superoxide radicals, thereby demonstrating the effective light-activated therapy.
      Although the positively charged QDs demonstrate large cellular uptake, they bind
      indiscriminately to cell surfaces and cause non-selective cell death, while
      negatively charged and zwitterionic QD ligands reduce the uptake and allow
      selective therapeutic action via interaction with redox species. The stability of
      designed QDs in biologically-relevant media increases with the formation of core
      shell QD structures, but an appropriate design of core-shell structures is needed
      to minimize any reduction in charge injection efficiency to adsorbed oxygen
      molecules (to form superoxide) and maintain similar quantitative generation of
      tailored redox species, as measured using electron paramagnetic resonance (EPR)
      spectroscopy and electrochemical impedance spectroscopy (EIS). Using these
      findings, we demonstrate the rational design of QDs as selective therapeutic to
      kill more than 99% of a priority class I pathogen, thus providing an effective
      therapy against MDR superbugs.

PMID- 29594098
TI  - High-Power-Density, High-Energy-Density Fluorinated Graphene for Primary Lithium
      Batteries.
AB  - Li/CFx is one of the highest-energy-density primary batteries; however, poor rate
      capability hinders its practical applications in high-power devices. Here we
      report a preparation of fluorinated graphene (GFx) with superior performance
      through a direct gas fluorination method. We find that the so-called "semi-ionic"
      C-F bond content in all C-F bonds presents a more critical impact on rate
      performance of the GFx in comparison with sp2 C content in the GFx, morphology,
      structure, and specific surface area of the materials. The rate capability
      remains excellent before the semi-ionic C-F bond proportion in the GFx decreases.
      Thus, by optimizing semi-ionic C-F content in our GFx, we obtain the optimal x of
      0.8, with which the GF0.8 exhibits a very high energy density of 1,073 Wh kg-1
      and an excellent power density of 21,460 W kg-1 at a high current density of 10 A
      g-1. More importantly, our approach opens a new avenue to obtain fluorinated
      carbon with high energy densities without compromising high power densities.

PMID- 29594099
TI  - Anthocyanin Biosynthesis and Degradation Mechanisms in Solanaceous Vegetables: A
      Review.
AB  - Anthocyanins are a group of polyphenolic pigments that are ubiquitously found in
      the plant kingdom. In plants, anthocyanins play a role not only in reproduction,
      by attracting pollinators and seed dispersers, but also in protection against
      various abiotic and biotic stresses. There is accumulating evidence that
      anthocyanins have health-promoting properties, which makes anthocyanin metabolism
      an interesting target for breeders and researchers. In this review, the state of
      the art knowledge concerning anthocyanins in the Solanaceous vegetables, i.e.,
      pepper, tomato, eggplant, and potato, is discussed, including biochemistry and
      biological function of anthocyanins, as well as their genetic and environmental
      regulation. Anthocyanin accumulation is determined by the balance between
      biosynthesis and degradation. Although the anthocyanin biosynthetic pathway has
      been well-studied in Solanaceous vegetables, more research is needed on the
      inhibition of biosynthesis and, in particular, the anthocyanin degradation
      mechanisms if we want to control anthocyanin content of Solanaceous vegetables.
      In addition, anthocyanin metabolism is distinctly affected by environmental
      conditions, but the molecular regulation of these effects is poorly understood.
      Existing knowledge is summarized and current gaps in our understanding are
      highlighted and discussed, to create opportunities for the development of
      anthocyanin-rich crops through breeding and environmental management.

PMID- 29594100
TI  - Ursolic Acid Hydrazide Based Organometallic Complexes: Synthesis,
      Characterization, Antibacterial, Antioxidant, and Docking Studies.
AB  - In thecurrent research work,eleven metal complexes were synthesized from the
      hydrazide derivative of ursolic acid. Metal complexes of tin, antimony and iron
      were synthesized and characterized by FT-IR and NMR spectroscopy. The
      antibacterial and antioxidant activities were performed for these complexes,
      which revealed that the metal complexes synthesized are more potent than their
      parent compounds. We observed that antioxidant activity showed by triphenyltin
      complex was significant and least activity have been shown by antimony
      trichloride complex. The synthesized metal complexes were then evaluated against
      two Gram-negative and two Gram-positive bacterial strains. Triphenyl tin complex
      emerged as potent antibacterial agent with MIC value of 8 MUg/ml each against
      Shigellaspp, Salmonella typhi and Staphylococcus aureus. While, the MIC value
      against Streptococcus pneumoniae is 4 MUg/ml. Computational docking studies were
      carried out on molecular targets to interpret the results of antioxidant and
      antibacterial activities. Based on the results, it may be inferred that the metal
      complexes of ursolic acid are more active as compared to the parent drug and may
      be proved for some other pharmacological potential by further analysis.

PMID- 29594102
TI  - Facile Fabrication of BiOI/BiOCl Immobilized Films With Improved Visible Light
      Photocatalytic Performance.
AB  - HIGHLIGHTS A facial method was used to fabricate BiOI/BiOCl film at room
      temperature.30% BiOI/BiOCl showed an excellent photocatalytic activity and
      stability.Improvement of photocatalytic activity was owed to expanded visible
      light absorption and high separation efficiency of charge. Photocatalysis has
      been considered to be one of the most promising ways to photodegrade organic
      pollutants. Herein, a series of BiOI/BiOCl films coating on FTO were fabricated
      through a simple method at room temperature. The photocatalytic efficiency of
      30%BiOI/BiOCl could reach more than 99% aiming to degrading RhB and MB after 90
      and 120 min, respectively. Compared with BiOCl, 30%BiOI/BiOCl showed 12 times
      higher efficiency when degrading RhB. In comparison with BiOI, 30%BiOI/BiOCl
      showed 5 and 6 times higher efficiency when degrading RhB and MB, respectively.
      These obvious enhancements were attributed to expanded visible light absorption
      and high separation performance of photoinduced charge. Moreover, the
      photocatalytic activity of 30%BiOI/BiOCl had no obvious decrease after five
      recycles, suggesting that it was a promising photocatalyst for the removal of MB
      and RhB pollutants. Finally, the possible growth process for the BiOI/BiOCl thin
      films and photocatalysis mechanism were investigated in details. This work would
      provide insight to the reasonable construction of BiOX heterojunction and the
      photocatalytic mechanism in degrading organic pollutants.

PMID- 29594104
TI  - Lymphocytic Lobular Panniculitis: A Diagnostic Challenge.

PMID- 29594105
TI  - Neutrophilic Dermatoses in Autoimmune Diseases: Report of Two Cases Associated
      with Autoimmune Thyroiditis.
AB  - The term "neutrophilic dermatoses" includes a rare inflammatory pattern
      characterized by neutrophil-rich cutaneous infiltrate. Both innate and adaptive
      immune pathways may be involved in neutrophil recruitment. Occasionally,
      neutrophilic dermatoses may occur in association with autoimmune thyroiditis.
      Pathogenetic aspects of this autoimmune disorder may elucidate their possible
      connection. Two exemplificative cases are taken as a pretext for a short review
      of this topic.

PMID- 29594101
TI  - Computer-Aided Drug Design in Epigenetics.
AB  - Epigenetic dysfunction has been widely implicated in several diseases especially
      cancers thus highlights the therapeutic potential for chemical interventions in
      this field. With rapid development of computational methodologies and high
      performance computational resources, computer-aided drug design has emerged as a
      promising strategy to speed up epigenetic drug discovery. Herein, we make a brief
      overview of major computational methods reported in the literature including
      druggability prediction, virtual screening, homology modeling, scaffold hopping,
      pharmacophore modeling, molecular dynamics simulations, quantum chemistry
      calculation, and 3D quantitative structure activity relationship that have been
      successfully applied in the design and discovery of epi-drugs and epi-probes.
      Finally, we discuss about major limitations of current virtual drug design
      strategies in epigenetics drug discovery and future directions in this field.

PMID- 29594103
TI  - Chloride Ion Transport by the E. coli CLC Cl-/H+ Antiporter: A Combined Quantum
      Mechanical and Molecular-Mechanical Study.
AB  - We performed steered molecular dynamics (SMD) and umbrella sampling simulations
      of Cl- ion migration through the transmembrane domain of a prototypical E. coli
      CLC Cl-/H+ antiporter by employing combined quantum-mechanical (QM) and molecular
      mechanical (MM) calculations. The SMD simulations revealed interesting
      conformational changes of the protein. While no large-amplitude motions of the
      protein were observed during pore opening, the side chain rotation of the
      protonated external gating residue Glu148 was found to be critical for full
      access of the channel entrance by Cl-. Moving the anion into the external binding
      site (Sext) induced small-amplitude shifting of the protein backbone at the N
      terminal end of helix F. As Cl- traveled through the pore, rigid-body swinging
      motions of helix R separated it from helix D. Helix R returned to its original
      position once Cl- exited the channel. Population analysis based on polarized
      wavefunction from QM/MM calculations discovered significant (up to 20%) charge
      loss for Cl- along the ion translocation pathway inside the pore. The delocalized
      charge was redistributed onto the pore residues, especially the functional groups
      containing pi bonds (e.g., the Tyr445 side chain), while the charges of the H
      atoms coordinating Cl- changed almost negligibly. Potentials of mean force
      computed from umbrella sampling at the QM/MM and MM levels both displayed
      barriers at the same locations near the pore entrance and exit. However, the
      QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol).
      Binding energy calculations indicated that the interactions between Cl- and
      certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian
      and underestimated by the CHARMM36 force fields, both of which were employed in
      the umbrella sampling simulations. In particular, CHARMM36 underestimated binding
      interactions for the functional groups containing pi bonds, missing the
      stabilizations of the Cl- ion due to electron delocalization. The results
      suggested that it is important to explore these quantum effects for accurate
      descriptions of the Cl- transport.

PMID- 29594106
TI  - Gangrenous Chickenpox with Atypical Clinical and Histopathological Findings.

PMID- 29594107
TI  - Effects of Enteral Immunonutrition in Esophageal Cancer.
AB  - Background: Immunonutrition (IN) significantly reduces the incidence of
      postoperative infectious complications and the length of hospitalization in
      patients undergoing major elective surgery for gastrointestinal malignances.
      However, the clinical benefit of IN in patients who have undergone esophagectomy
      for esophageal cancer is unclear. Moreover, the effect of enteral IN in patients
      during preoperative adjuvant chemoradiotherapy and in patients treated with
      concurrent chemoradiotherapy for advanced esophageal cancer is unknown. Summary:
      This review analyzes the evidence supporting the enteral administration of IN in
      patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal
      cancer. Twelve trials that evaluated IN exclusively in patients who underwent
      esophagectomy were published between January 1980 and August 2017. Two trials
      concerning IN during chemoradiotherapy for esophageal cancer were identified in
      the same period. However, the evidence is insufficient to recommend enteral IN in
      patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal
      cancer. Key Message: Further evidence from well-designed randomized controlled
      trials is required to verify the clinical benefits of enteral IN in patients
      undergoing esophagectomy and/or chemoradiotherapy for esophageal cancer.
      Practical Implications: Resolvins, which are generated from EPA, are novel anti
      inflammatory lipid mediators and may play a key role in the resolution of acute
      inflammation when IN is supplemented with EPA in patients undergoing severely
      stressful operations.

PMID- 29594108
TI  - Short-Term Outcomes of Extended Pancreatectomy: A Single-Surgeon Experience.
AB  - Background/Aims: The International Study Group of Pancreatic Surgery recently
      published a consensus statement on the definition of extended pancreatectomy
      (EP). We aimed to determine the safety profile and short-term outcomes of EP
      compared to standard pancreatectomy (SP). To mitigate surgeon bias, only
      pancreatectomies performed by a single surgeon were included. Methods: Ninety
      consecutive patients who underwent pancreatectomy by a single surgeon over a
      period of 5 years and who met our study criteria were classified into an SP or an
      EP group. Sixty-two patients underwent pancreaticoduodenectomy (PD), including
      total pancreatectomy, and 28 patients underwent distal pancreatectomy. Results:
      The 25 patients who underwent EP had significantly increased operation time,
      estimated blood loss, postoperative intensive care unit (ICU) transfer, and
      postoperative stay compared to the 65 patients who underwent SP. There was 1
      (1.1%) 30-day mortality and 4 (4.4%) in-hospital mortalities. Postoperative
      morbidity and mortality were similar between both groups. Subgroup analysis of
      the patients who underwent PD demonstrated that the EP group (n = 22) had
      significantly increased operation time and postoperative ICU transfers.
      Conclusion: Although patients who underwent EP experienced significantly
      increased operative time, blood loss, and postoperative stay, they did not
      experience significantly higher postoperative morbidity or mortality compared to
      patients who underwent SP.

PMID- 29594109
TI  - Impact of Three-Dimensional Surgical Simulation on Pancreatic Surgery.
AB  - Background/Aims: Anatomical variations are frequently encountered during hepato
      biliary-pancreatic surgeries, requiring surgeons to have a precise understanding
      of the surgical anatomy in order to perform a safe surgery. We evaluated the
      impact of novel three-dimensional (3D) surgical simulation on pancreatic
      surgeries to enhance surgical residents' understanding. Methodology: Between
      January 2013 and May 2014, 61 preoperative 3D surgical simulations were
      performed. The consistency (0-10, with 10 representing 100% consistency) among
      the 15 surgical residents' anatomical drawings from multidetector computed
      tomography images and the simulated 3D images by SYNAPSE VINCENT(r) was assessed.
      We divided the surgical residents into two groups - first- to fifth-year
      postgraduate doctors (group A) and sixth- to tenth-year postgraduate doctors
      (group B) - and compared the self-assessment scores between these two groups.
      Results: In terms of the self-assessment scores, a statistically significant
      difference was observed between the two groups (p < 0.001). Conclusions: In this
      study, 3D surgical simulation was useful for preoperative assessments prior to
      pancreatic surgery, especially in younger postgraduate surgeons.

PMID- 29594110
TI  - Is Colonoscopy Indicated in Young Patients with Hematochezia.
AB  - Background/Aims: While colonoscopy is indicated in patients >50 years old
      presenting with hematochezia, its role in those <=50 remains debatable. This
      study aims to evaluate the role of colonoscopy in patients presenting with
      hematochezia who are <=50 years old. Methods: A retrospective review of all
      patients aged <=50 years who underwent colonoscopy for hematochezia in 2012 was
      conducted. Patient demographics, endoscopic details, and histological results
      were analyzed. Patients were stratified by age to compare differences in outcome.
      Results: A total of 361 patients with a median age of 44 (range, 18-50) years
      were reviewed. Hemorrhoid (n = 183, 69.6%) was the most common etiology. Seventy
      two neoplastic polyps were identified in 48 (13.3%) patients. There was a
      significantly larger proportion of patients aged 41-50 years who had neoplastic
      polyps compared to those aged <=40 (18.8 vs. 3.8%, p <= 0.001); 43.8% (n = 28) of
      the neoplastic polyps found in those aged 41-50 were proximal to the splenic
      flexure. The only 2 (0.5%) patients with malignancy were aged 41-50 years.
      Conclusion: Performing colonoscopy in patients presenting with hematochezia
      should be strongly considered for those aged 41-50 years in view of the
      significant likelihood of underlying neoplastic polyps compared to those aged
      <=40 years.

PMID- 29594111
TI  - Waiting Time following Neoadjuvant Chemoradiotherapy for Rectal Cancer: Does It
      Really Matter.
AB  - Background: Neoadjuvant chemoradiotherapy (CRT) is considered the standard
      approach before any surgical intervention for locally advanced rectal tumors and
      has been proven to significantly improve the local recurrence rates of rectal
      cancer. However, the optimal timing of surgical resection after neoadjuvant CRT
      remains debatable. Objective and Methods: We conducted a retrospective review of
      65 consecutive patients with locally advanced rectal cancer who underwent
      preoperative CRT followed by surgical resection in order to evaluate the optimal
      time for surgical treatment. We used two alternative groups for analysis:
      patients who underwent surgery up to 6 weeks after CRT (n = 28) and those who
      underwent surgery 6 weeks or more after CRT (n = 27). Also, we compared patients
      who were operated on within 3 months (n = 39) with those who underwent surgical
      resection after more than 3 months (n = 16). Nonresponders to CRT were excluded
      from the analysis. Results: There was no statistically significant association
      between waiting period post CRT and radiological downstaging for any group (p >
      0.05 for any association). Also, there was no association between recurrence of
      disease, cancer-related deaths, perineural invasion, or positive lymph node ratio
      and any waiting period up to 3 months (p > 0.05 for all associations).
      Conclusion: In this small exploratory study there was no evident difference in
      outcome according to timing of surgery, which suggests that further research in
      larger cohorts is warranted.

PMID- 29594112
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000442831.].

PMID- 29594113
TI  - Interplay of Inflammatory Mediators with Epigenetics and Cartilage Modifications
      in Osteoarthritis.
AB  - Osteoarthritis (OA), a degenerative disease of diarthrodial joints, is influenced
      by mechanical and inflammatory factors with aging, obesity, chronic injuries, and
      secondary diseases thought to be major factors driving the process of articular
      cartilage degeneration. Chondrocytes, the cellular component of cartilage, reside
      in an avascular environment and normally have limited potential to replicate.
      However, extrinsic factors such as injury to the joint or intrinsic alterations
      to the chondrocytes themselves can lead to an altered phenotype and development
      of OA. Synovial inflammation is also a pivotal element of the osteoarthritic,
      degenerative process: influx of pro-inflammatory cytokines and production of
      matrix metalloproteinases accelerate advanced cellular processes such as
      synovitis and cartilage damage. As well as a genetic input, recent data have
      highlighted epigenetic factors as contributing to disease. Studies conducted over
      the last decade have focused on three key aspects in OA; inflammation and the
      immune response, genome-wide association studies that have identified important
      genes undergoing epigenetic modifications, and finally how chondrocytes transform
      in their function during development and disease. Data highlighted here have
      identified critical inflammatory genes involved in OA and how these factors
      impact chondrocyte hypertrophy in the disease. This review also addresses key
      inflammatory factors in synovial inflammation, epigenetics, and chondrocyte fate,
      and how agents that inhibit epigenetic mechanisms like DNA methylation and
      histone modifications could aid in development of long-term treatment strategies
      for the disease.

PMID- 29594115
TI  - Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert
      Consensus.
AB  - Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has
      become available in the last 10 years and has greatly improved patients' quality
      of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant
      C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and
      a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good
      response is maintained over repeated treatments and several years. All currently
      available prophylactic agents are associated with breakthrough attacks, therefore
      an acute treatment plan is essential for every patient. Experience has shown that
      higher doses of C1 inhibitor than previously recommended may be desirable,
      although only recombinant C1 inhibitor has been subject to full dose-response
      evaluation. Treatment of early symptoms of an attack, with any licensed therapy,
      results in milder symptoms, more rapid resolution and shorter duration of attack,
      compared with later treatment. All therapies have been shown to be well
      tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors
      have a reassuring safety record regarding lack of transmission of virus or other
      infection. Thrombosis has been reported in association with plasma-derived C1
      inhibitor in some case series. Ruconest was associated with anaphylaxis in a
      single rabbit-allergic volunteer, but no further anaphylaxis has been reported in
      those not allergic to rabbits despite, in a few cases, prior IgE sensitization to
      rabbit or milk protein. Icatibant is associated with high incidence of local
      reactions but not with systemic effects. Ecallantide may cause anaphylactoid
      reactions and is given under supervision. For children and pregnant women, plasma
      derived C1 inhibitor has the best evidence of safety and currently remains first
      line treatment.

PMID- 29594114
TI  - Microenvironment-Cell Nucleus Relationship in the Context of Oxidative Stress.
AB  - The microenvironment is a source of reactive oxygen species (ROS) that influence
      cell phenotype and tissue homeostasis. The impact of ROS on redox pathways as
      well as directly on epigenetic mechanisms and the DNA illustrate communication
      with the cell nucleus. Changes in gene transcription related to redox conditions
      also influence the content and structure of the extracellular matrix. However,
      the importance of microenvironmental ROS for normal progression through life and
      disease development still needs to be thoroughly understood. We illustrate how
      different ROS concentration levels trigger various intracellular pathways linked
      to nuclear functions and determine processes necessary for the differentiation of
      stem cells. The abnormal predominance of ROS that leads to oxidative stress is
      emphasized in light of its impact on aging and diseases related to aging. These
      phenomena are discussed in the context of the possible contribution of
      extracellular ROS via direct diffusion into cells responsible for organ function,
      but also via an impact on stromal cells that triggers extracellular modifications
      and influences mechanotransduction. Finally, we argue that organs-on-a-chip with
      controlled microenvironmental conditions can help thoroughly grasp whether ROS
      production is readily a cause or a consequence of certain disorders, and better
      understand the concentration levels of extracellular ROS that are necessary to
      induce a switch in phenotype.

PMID- 29594116
TI  - Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus
      Infection.
AB  - Zika virus (ZIKV) disease has become a global health emergency with devastating
      effects on public health. Recent evidences implicate the virus as an emergent
      neuropathological agent promoting serious pathologies of the human nervous
      system, that include destructive and malformation consequences such as
      development of ocular and fetal brain lesions, microcephaly in neonates, and
      Guillain-Barre syndrome (GBS) in adults. These neurological disorders of both
      central and peripheral nervous systems are thought to be associated to the
      neurotropic properties of the virus that has ability to infect neural stem cells
      as well as peripheral neurons, a hallmark of its pathogenicity. The presence of
      autoantibodies against gangliosides plays a pivotal role in the etiogenesis of
      GBS and a variety of neurological disorders. Gangliosides are a class of
      galactose-containing cerebrosides mainly expressed in nervous system tissues
      playing a critical role in the physiology of neural cells and neurogenesis.
      Herein, our findings indicate that patients at acute phase of ZIKV infection
      without any neurological signs show increased levels of IgG autoantibody against
      GD3 gangliosides, a class of glycolipid found to be highly expressed in neural
      stem cell acting in the maintenance of their self-renewal cellular capacity. It
      is possible that a pathological threshold of these antibodies is only acquired in
      secondary or subsequent infections. In the light of these evidences, we propose
      that the target of GD3 by autoimmune responses may possibly has an effect in the
      neuropathy and neurogenesis disorder seen during ZIKV infection.

PMID- 29594117
TI  - Erythrocyte Salt Sedimentation Assay Does Not Predict Response to Renal
      Denervation.
AB  - Renal denervation (RDN) has recently been shown to be effective in patients
      without antihypertensive medication. However, about 30% of patients do not
      respond to RDN, and therefore, there exists a need to find predictors of
      response. Individuals are either salt-sensitive (SS) or non-salt-sensitive (NSS)
      in terms of their blood pressure (BP) regulation. The sympathetic nervous system
      can influence water and salt handling. RDN reduces sympathetic drive and has an
      impact on salt excretion. The present study was conducted to test the influence
      of salt sensitivity in terms of the BP reducing effect after RDN procedure. Salt
      sensitivity was estimated using the in vitro Erythrocyte Salt Sedimentation Assay
      (ESS). In 88 patients with resistant hypertension, RDN was performed. Office BP
      and lab testing were performed at baseline and at month 1, 3, 6, 12, 18, and 24
      after RDN. A responder rate of 64.7% has been observed. Salt sensitivity
      measurements (ESS-Test) were completed in a subgroup of 37 patients with
      resistant hypertension. In this group, 15 were SS and 17 were salt-resistant
      according to the in vitro assay, respectively. The responder rate was 60% in SS
      patients and 59.1% in NSS patients, respectively. Electrolytes as well as
      aldosterone and renin levels did not differ between the two groups at baseline
      and in the follow-up measurements. The present study showed that salt
      sensitivity, estimated using the ESS in vitro test, did not affect the outcome of
      RDN and, therefore, does not help to identify patients suitable for RDN.

PMID- 29594118
TI  - The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of
      Adrenocortical Tumor Heterogeneity.
AB  - Adrenal cortical tumors constitute a heterogeneous group of neoplasms with
      distinct clinical, morphological, and molecular features. Recent discoveries of
      specific genotype-phenotype correlations in adrenal cortical adenomas have
      transformed our understanding of their respective endocrine syndromes. Indeed, a
      proportion of patients with primary aldosteronism are now known to harbor adrenal
      cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1,
      ATP2B3, and CACNA1D) involving the calcium/calmodulin kinase signaling pathway.
      Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing
      adenomas have distinct clinicopathological phenotype compared to those harboring
      ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting
      with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS,
      PDE11A, and PDE8B) involving the cyclic AMP signaling pathway. In addition to
      cortisol-producing adenomas, bilateral micronodular adrenocortical disease and
      primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the
      spectrum of benign neoplasms causing adrenal Cushing disease. The recent
      discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the
      old belief that this disorder is mainly a sporadic disease. Emerging evidence
      suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting
      the heterogeneous genomic landscape of this disease. Although most solitary
      adrenal cortical tumors are sporadic, there is an increasing recognition that
      inherited susceptibility syndromes may also play a role in their pathogenesis.
      This review highlights the molecular and morphological heterogeneity of benign
      adrenal cortical neoplasms, reflected in the diverse presentations of primary
      aldosteronism and adrenal Cushing syndrome.

PMID- 29594120
TI  - The Safety and Efficacy of the Continuous Peripheral Nerve Block in Postoperative
      Analgesia of Pediatric Patients.
AB  - Postoperative analgesia is imperative in the youngest patients. Pain, especially
      if experienced during childhood, has numerous adverse effects-from psychological,
      through complications of the underlying disease (prolonged treatment, hospital
      stay, and increased costs of the treatment) to an increase in the incidence of
      death due to the onset of the systemic inflammatory response. Peripheral blocks
      provide analgesia for 12-16 h, and are safer due to rare side effects that are
      easier to treat. The continuous peripheral block (CPNB) has been increasingly
      used in recent years for complete and prolonged analgesia of pediatric patients,
      as well as a part of multidisciplinary treatment of complex regional pain
      syndrome. It has been shown that outpatient CPNB reduces the need for parenteral
      administration of opioid analgetics. It has also been proved that this technique
      can be used in pediatric patients in home conditions. Safety of CPNB is based on
      the increasing use of ultrasound as well as on the introduction of single
      enantiomers local anesthetics (ropivacaine and levobupivacaine) in lower
      concentrations. It is possible to discharge patient home with catheter, but it is
      necessary to provide adequate education for staff, patients, and parents, as well
      as to have dedicated anesthesiology team. Postoperative period without major pain
      raises the morale of the child, parents. and medical staff.

PMID- 29594119
TI  - Monogenic Causes of Proteinuria in Children.
AB  - Glomerular disease is a common cause for proteinuria and chronic kidney disease
      leading to end-stage renal disease requiring dialysis or kidney transplantation
      in children. Nephrotic syndrome in children is diagnosed by the presence of a
      triad of proteinuria, hypoalbuminemia, and edema. Minimal change disease is the
      most common histopathological finding in children and adolescents with nephrotic
      syndrome. Focal segmental sclerosis is also found in children and is the most
      common pathological finding in patients with monogenic causes of nephrotic
      syndrome. Current classification system for nephrotic syndrome is based on
      response to steroid therapy as a majority of patients develop steroid sensitive
      nephrotic syndrome regardless of histopathological diagnosis or the presence of
      genetic mutations. Recent studies investigating the genetics of nephrotic
      syndrome have shed light on the pathophysiology and mechanisms of proteinuria in
      nephrotic syndrome. Gene mutations have been identified in several subcellular
      compartments of the glomerular podocyte and play a critical role in mitochondrial
      function, actin cytoskeleton dynamics, cell-matrix interactions, slit diaphragm,
      and podocyte integrity. A subset of genetic mutations are known to cause
      nephrotic syndrome that is responsive to immunosuppressive therapy but clinical
      data are limited with respect to renal prognosis and disease progression in a
      majority of patients. To date, more than 50 genes have been identified as
      causative factors in nephrotic syndrome in children and adults. As genetic
      testing becomes more prevalent and affordable, we expect rapid advances in our
      understanding of mechanisms of proteinuria and genetic diagnosis will help direct
      future therapy for individual patients.

PMID- 29594121
TI  - Echinococcus granulosus: Cure for Cancer Revisited.
AB  - Whereas a number of parasites are well recognized risk factors for a number of
      different cancers in mammalian hosts, there is limited information on the ability
      of parasitic organisms to induce anticancer effects. There are conflicting
      reports that echinococcosis, caused by the canine tapeworm Echinococcus
      granulosus, can decrease or increase cancer risk. This review considers both
      indirect anticancer effects as the result of adaptive immunity generated against
      certain echinococcal antigens and the direct effect of molecules released by E.
      granulosus whose activity directly inhibits cancer cell migration and growth. In
      conclusion, E. granulosus probably secretes molecules that can be developed as
      anticancer therapeutics in future.

PMID- 29594123
TI  - Getting Digital Assets from Public-Private Partnership Research Projects through
      "The Valley of Death," and Making Them Sustainable.
AB  - Projects in public-private partnerships, such as the Innovative Medicines
      Initiative (IMI), produce data services and platforms (digital assets) to help
      support the use of medical research data and IT tools. Maintaining these assets
      beyond the funding period of a project can be a challenge. The reason for that is
      the need to develop a business model that integrates the perspectives of all
      different stakeholders involved in the project, and these digital assets might
      not necessarily be addressing a problem for which there is an addressable market
      of paying customers. In this manuscript, we review four IMI projects and the
      digital assets they produced as a means of illustrating the challenges in making
      digital assets sustainable and the lessons learned. To progress digital assets
      beyond proof-of-concept into widely adopted tools, there is a need for
      continuation of multi-stakeholder support tailored to these assets. This would be
      best done by implementing a structure similar to the accelerators that are in
      place to help transform startup businesses into growing and thriving businesses.
      The aim of this article is to highlight the risk of digital asset loss and to
      provoke discussion on the concept of developing an "accelerator" for digital
      assets from public-private partnership research projects to increase the chance
      that digital assets will be sustained and continue to add value long after a
      project has ended.

PMID- 29594124
TI  - Precision Medicine and Global Health: The Good, the Bad, and the Ugly.

PMID- 29594122
TI  - Comorbidities in Spondyloarthritis.
AB  - Comorbidities in spondyloarthritis (SpA) add to the burden of disease by
      contributing to disease activity, functional and work disability, and mortality.
      Thus, awareness of comorbidities in SpA is crucial to improve their screening and
      management and to ultimately improve outcomes in those affected. Osteoporosis has
      been reported to be the most prevalent comorbidity in SpA, and its risk is
      increased in these patients, compared with the general population; the risk of
      vertebral fractures requires further evaluation. Cardiovascular risk is also
      increased in this population, both due to an increase of the traditional
      cardiovascular risk factors in these patients, but also due to the presence of
      inflammation. The role of non-steroidal anti-inflammatory drugs in this increased
      risk needs further elucidation, but there is consensus on the need to encourage
      smoking cessation and to perform periodic evaluation of cardiovascular risk in
      these patients, particularly in the case of change in treatment course.
      Concerning the risk of cancer, no increased risk inherent to SpA seems to exist.
      However, an increased neoplastic risk can occur due to SpA treatments, e.g., P
      UVA. Data are sparse on the risk of infections compared with rheumatoid
      arthritis, but there appears to be no risk in the absence of TNF-inhibitor
      exposure. Regardless of which comorbidity, a gap exists between recommendations
      for their management and actual implementation in clinical practice, suggesting
      that there is still a need for improvement in this area. Systematic screening for
      these comorbidities should improve both short- and long-term outcomes in SpA
      patients.

PMID- 29594125
TI  - Attribution of Neuropsychiatric Manifestations to Systemic Lupus Erythematosus.
AB  - Neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE) is one of
      the most severe manifestations of the disease that has a heavy impact on
      patient's functioning, quality of life, and disease outcome. The prevalence is
      highly variable and the clinical phenotypes vary from common syndromes to rare NP
      entities. Its occurrence may be the result of a primary manifestation of SLE,
      secondary to other conditions (such as infections or metabolic disturbances) or
      the effect of concomitant comorbidities that often complicate the disease course.
      Correct attribution of NP events may pose diagnostic challenges and it is a
      critical factor in selecting the correct management. Although there is still no
      diagnostic gold standard to rightly diagnose NPSLE syndromes, great advances have
      been made in improving the clinician judgment in the evaluation process. In this
      narrative review, we present and discuss available evidence concerning NPSLE with
      a special focus on the attribution models developed using composite decision
      rules to ascribe NP events to SLE.

PMID- 29594126
TI  - Emerging Infectious Agents and Blood Safety in Latin America.
AB  - Historically, emerging infectious agents have been an important driving force
      toward the enhancement of blood safety, illustrated by the sharp reduction in the
      transmission of infectious agents by blood transfusion after human
      immunodeficiency virus (HIV) epidemics. In general, Latin American (LATAM)
      countries have introduced screening for microorganisms with proven blood
      transmission with some delay in comparison to developed countries, but, nowadays,
      all LATAM countries comply with a minimum standard of screening which includes
      Hepatitis B, C, HIV, Treponema pallidum, and Trypanosoma cruzi. Noticeably, all
      those agents, in addition to HTLV, cause chronic infections. By contrast, in the
      last decade, the region has witnessed explosive outbreaks of arboviral diseases,
      representing a new challenge to the blood system, threatening not only blood
      safety but also availability. So far, the clinical impact of transfusion
      transmitted Dengue, Chikungunya, or Zika has not been evident, precluding
      immediate reaction from the authorities. A number of other arboviruses are
      endemic in the region and may, unpredictably, originate new epidemics. Several
      measures must be taken in preparedness for the potential emergence of another
      arbodisease.

PMID- 29594127
TI  - Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Myogenesis and
      Mitochondrial Biosynthesis during Murine Skeletal Muscle Cell Differentiation.
AB  - Polyunsaturated fatty acids are important nutrients for human health, especially
      omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA), which have been found to play positive roles in the prevention of various
      diseases. However, previous studies have reported that excessive omega-3 fatty
      acids supplement during pregnancy caused side effects such as slower neural
      transmission times and postnatal growth restriction. In this study, we
      investigated the effect of EPA and DHA on mitochondrial function and gene
      expression in C2C12 myoblasts during skeletal muscle differentiation. C2C12
      myoblasts were cultured to confluency and then treated with differentiation
      medium that contained fatty acids (50-uM EPA and DHA). After 72 h of myogenic
      differentiation, mRNA was collected, and gene expression was analyzed by real
      time PCR. Microscopy was used to examine cell morphology following treatment with
      fatty acids. The effect of EPA and DHA on cellular oxygen consumption was
      measured using a Seahorse XF24 Analyzer. Cells treated with fatty acids had fewer
      myotubes formed (P <= 0.05) compared with control cells. The expression of the
      genes related to myogenesis was significantly lower (P <= 0.05) in cells treated
      with fatty acids, compared with control cells. Genes associated with adipogenesis
      had higher (P <= 0.05) expression after treatment with fatty acids. Also, the
      mitochondrial biogenesis decreased with lower (P <= 0.05) gene expression and
      lower (P <= 0.05) mtDNA/nDNA ratio in cells treated with fatty acids compared
      with control cells. However, the expression of genes related to peroxisome
      biosynthesis was higher (P <= 0.05) in cells treated with fatty acids. Moreover,
      fatty-acid treatment reduced (P <= 0.05) oxygen consumption rate under oligomycin
      inhibited (reflecting proton leak) and uncoupled conditions. Our data imply that
      fatty acids might reduce myogenesis and increase adipogenesis in myotube
      formation. Fatty acids may also decrease cell metabolism by reducing
      mitochondrial biogenesis as well as respiration rate. This study suggests that
      the maternal overdosage of EPA and DHA may influence fetal muscle development,
      increase intramuscular adipose tissue deposition in offspring, and have a long
      term effect on the development of metabolic diseases such as obesity and diabetes
      in adult offspring.

PMID- 29594128
TI  - Preadministration of Fermented Sorghum Diet Provides Protection against
      Hyperglycemia-Induced Oxidative Stress and Suppressed Glucose Utilization in
      Alloxan-Induced Diabetic Rats.
AB  - Sorghum bicolor grains are rich in phytochemicals known to considerably impact
      human health. Several health-promoting products such as flour, staple food, and
      beverages have been produced from sorghum grains. This study investigated the
      protective and modulatory effects of a sorghum diet on the genes of some
      antioxidant and glycolytic enzymes in alloxan-induced diabetic rats. The rats
      were randomly distributed into six groups: the control group received normal
      diet, while the other groups were pretreated with 12.5, 25, 50, 75, and 100% of
      the sorghum diets daily for 8 weeks before the administration of a dose of
      alloxan (100 mg/kg BW), after which blood was collected and the liver was
      excised. The effects of the diets on blood glucose levels, liver dysfunction
      indices, and markers of oxidative stress were assessed spectrophotometrically,
      while the gene expressions of key glycolytic enzymes and enzymatic antioxidants
      were assayed using reverse transcriptase polymerase chain reaction. It was
      observed that the pretreatment of the experimental animals with the diets
      normalized the blood glucose before and after the administration of alloxan. The
      sorghum-treated groups also showed statistically significant (p < 0.05) decrease
      in liver dysfunction indices and markers of oxidative damage compared with the
      control. In addition, statistically the diets significantly decreased (p < 0.05)
      the relative expression of superoxide dismutase, glutathione peroxidase,
      glucokinase, phosphofructokinase, and hexokinase genes in the experimental
      animals compared with the control. Overall, this study showed that the
      preadministration of fermented sorghum diet significantly protected against
      hyperglycemia and suppressed glucose utilization via glycolysis in the liver of
      alloxan-induced diabetic rats. Thus, the consumption of sorghum diet may protect
      against hyperglycemia and oxidative damage and may therefore serve as functional
      food for management of diabetic mellitus.

PMID- 29594130
TI  - Rubisco Assembly in the Chloroplast.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate
      limiting step in the Calvin-Benson cycle, which transforms atmospheric carbon
      into a biologically useful carbon source. The slow catalytic rate of Rubisco and
      low substrate specificity necessitate the production of high levels of this
      enzyme. In order to engineer a more efficient plant Rubisco, we need to better
      understand its folding and assembly process. Form I Rubisco, found in green algae
      and vascular plants, is a hexadecamer composed of 8 large subunits (RbcL),
      encoded by the chloroplast genome and 8 small, nuclear-encoded subunits (RbcS).
      Unlike its cyanobacterial homolog, which can be reconstituted in vitro or in E.
      coli, assisted by bacterial chaperonins (GroEL-GroES) and the RbcX chaperone,
      biogenesis of functional chloroplast Rubisco requires Cpn60-Cpn20, the
      chloroplast homologs of GroEL-GroES, and additional auxiliary factors, including
      Rubisco accumulation factor 1 (Raf1), Rubisco accumulation factor 2 (Raf2) and
      Bundle sheath defective 2 (Bsd2). The discovery and characterization of these
      factors paved the way for Arabidopsis Rubisco assembly in E. coli. In the present
      review, we discuss the uniqueness of hetero-oligomeric chaperonin complex for
      RbcL folding, as well as the sequential or concurrent actions of the post
      chaperonin chaperones in holoenzyme assembly. The exact stages at which each
      assembly factor functions are yet to be determined. Expression of Arabidopsis
      Rubisco in E. coli provided some insight regarding the potential roles for Raf1
      and RbcX in facilitating RbcL oligomerization, for Bsd2 in stabilizing the
      oligomeric core prior to holoenzyme assembly, and for Raf2 in interacting with
      both RbcL and RbcS. In the long term, functional characterization of each known
      factor along with the potential discovery and characterization of additional
      factors will set the stage for designing more efficient plants, with a greater
      biomass, for use in biofuels and sustenance.

PMID- 29594131
TI  - A Genome-Wide Search for Bipolar Disorder Risk Loci Modified by Mitochondrial
      Genome Variation.
AB  - Mitochondrial DNA mutations have been reported to be associated with bipolar
      disorder (BD). In this study, we performed genome-wide analyses to assess
      mitochondrial single-nucleotide polymorphism (mtSNP) effects on BD risk and early
      onset BD (EOBD) among BD patients, focusing on interaction effects between
      nuclear SNPs (nSNPs) and mtSNPs. Common nSNP and mtSNP data from European
      American BD cases (n = 1,001) and controls (n = 1,034) from the Genetic
      Association Information Network BD study were analyzed to assess the joint effect
      of nSNP and nSNP-mtSNP interaction on the risk of BD and EOBD. The effect of nSNP
      mtSNP interactions was also assessed. For BD risk, the strongest evidence of an
      association was obtained for nSNP rs1880924 in MGAM and mtSNP rs3088309 in CytB
      (pjoint = 8.2 * 10-8, pint = 1.4 * 10-4). Our results also suggest that the minor
      allele of the nSNP rs583990 in CTNNA2 increases the risk of EOBD among carriers
      of the mtSNP rs3088309 minor allele, while the nSNP has no effect among those
      carrying the mtSNP major allele (OR = 4.53 vs. 1.05, pjoint = 2.1 * 10-7, pint =
      1.16 * 10-6). While our results are not statistically significant after multiple
      testing correction and a large-sample replication is required, our exploratory
      study demonstrates the potential importance of considering the mitochondrial
      genome for identifying genetic factors associated with BD.

PMID- 29594129
TI  - Chromatin-Bound Cullin-Ring Ligases: Regulatory Roles in DNA Replication and
      Potential Targeting for Cancer Therapy.
AB  - Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligases (CRLs), the
      largest family of E3 ubiquitin ligases, are functional multi-subunit complexes
      including substrate receptors, adaptors, cullin scaffolds, and RING-box proteins.
      CRLs are responsible for ubiquitination of ~20% of cellular proteins and are
      involved in diverse biological processes including cell cycle progression, genome
      stability, and oncogenesis. Not surprisingly, cullins are deregulated in many
      diseases and instances of cancer. Recent studies have highlighted the importance
      of CRL-mediated ubiquitination in the regulation of DNA replication/repair,
      including specific roles in chromatin assembly and disassembly of the replication
      machinery. The development of novel therapeutics targeting the CRLs that regulate
      the replication machinery and chromatin in cancer is now an attractive
      therapeutic strategy. In this review, we summarize the structure and assembly of
      CRLs and outline their cellular functions and their diverse roles in cancer,
      emphasizing the regulatory functions of nuclear CRLs in modulating the DNA
      replication machinery. Finally, we discuss the current strategies for targeting
      CRLs against cancer in the clinic.

PMID- 29594132
TI  - Interleukin-17 Alteration in First-Episode Psychosis: A Meta-Analysis.
AB  - Schizophrenia is accompanied with central nervous system and peripheral immune
      system imbalances. Interleukin-17 (IL-17) is implicated in various immune and
      inflammatory processes. Aberrant levels of IL-17 have been reported in patients
      with schizophrenia, whereas the results are not consistent. To clarify the
      relationship between IL-17 and schizophrenia, we performed a meta-analysis in
      this study. We carried out a structured literature search in PubMed and Embase
      database up to April 16, 2017, and retrieved all eligible case-control studies
      according to the inclusion criteria. Finally, a total of 313 patients with drug
      naive first-episode psychosis and 238 healthy control subjects from 5 studies
      were included in our meta-analysis. There were no significant differences between
      first-episode psychosis patients and healthy controls with respect to the levels
      of IL-17 (p = 0.21), even when we removed 2 studies which were not European
      samples (p = 0.12). Our findings suggested that IL-17 may not be involved in the
      pathological mechanism of schizophrenia.

PMID- 29594133
TI  - Improved Scalability of Neuron-Based Phenotypic Screening Assays for Therapeutic
      Discovery in Neuropsychiatric Disorders.
AB  - There is a pressing need to improve approaches for drug discovery related to
      neuropsychiatric disorders (NSDs). Therapeutic discovery in neuropsychiatric
      disorders would benefit from screening assays that can measure changes in complex
      phenotypes linked to disease mechanisms. However, traditional assays that track
      complex neuronal phenotypes, such as neuronal connectivity, exhibit poor
      scalability and are not compatible with high-throughput screening (HTS)
      procedures. Therefore, we created a neuronal phenotypic assay platform that
      focused on improving the scalability and affordability of neuron-based assays
      capable of tracking disease-relevant phenotypes. First, using inexpensive
      laboratory-level automation, we industrialized primary neuronal culture
      production, which enabled the creation of scalable assays within functioning
      neural networks. We then developed a panel of phenotypic assays based on
      culturing of primary neurons from genetically modified mice expressing HTS
      compatible reporters that capture disease-relevant phenotypes. We demonstrated
      that a library of 1,280 compounds was quickly screened against both assays using
      only a few litters of mice in a typical academic laboratory setting. Finally, we
      implemented one assay in a fully automated high-throughput academic screening
      facility, illustrating the scalability of assays designed using this platform.
      These methodological improvements simplify the creation of highly scalable neuron
      based phenotypic assays designed to improve drug discovery in CNS disorders.

PMID- 29594134
TI  - The COMT Val158Met Polymorphism and Exploratory Behavior in Bipolar Mania.
AB  - Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences
      cognition and behavior in psychiatric illnesses; its low-activity allele,
      methionine (Met), may be associated with behavior reflecting catecholamine
      overactivity. Heightened motor activity and increased positive valence are
      central features of bipolar disorder (BD) and have been quantified in the human
      Behavioral Pattern Monitor (hBPM), an exploration paradigm based upon the rodent
      open field. We examined whether hBPM behavior was related to the COMT gene in a
      small sample of manic BD patients. Methods: Twenty-six acutely hospitalized manic
      BD patients were genotyped for the COMT Val158Met polymorphism and tested in the
      hBPM, an unfamiliar room containing novel objects. Movements around the hBPM and
      object interactions were video-recorded for 15 min and rated. Results: Met
      homozygote BD patients demonstrated significantly more interactions with multiple
      objects and more time spent with objects in the hBPM. Valine (Val) homozygote
      patients exhibited the least object exploration, while heterozygote patients
      demonstrated intermediate levels. Conclusion: This preliminary study suggests
      that arousal and positive valence are influenced in a linear fashion by COMT,
      presumably due to increased catecholamine in frontal regions, but these findings
      require replication in a larger sample. The hBPM can enable cross-species and
      transdiagnostic studies to inform neurobiology of psychiatric disorders.

PMID- 29594135
TI  - Mitochondrial Complex I Deficiency in Schizophrenia and Bipolar Disorder and
      Medication Influence.
AB  - Subjects with schizophrenia (SZ) and bipolar disorder (BD) show decreased protein
      and transcript levels for mitochondrial complex I. In vitro results suggest
      antipsychotic and antidepressant drugs may be responsible. We measured complex I
      activity in BD, SZ, and controls and presence of antipsychotic and antidepressant
      medications, mitochondrial DNA (mtDNA) copy number, and the mtDNA "common
      deletion" in the brain. Complex I activity in the prefrontal cortex was decreased
      by 45% in SZ compared to controls (p = 0.02), while no significant difference was
      found in BD. Complex I activity was significantly decreased (p = 0.01) in pooled
      cases (SZ and BD) that had detectable psychotropic medications and drugs compared
      to pooled cases with no detectable levels. Subjects with age at onset in their
      teens and psychotropic medications showed decreased (p < 0.05) complex I activity
      compared to subjects with an adult age at onset. Both SZ and BD groups displayed
      significant increases (p < 0.05) in mtDNA copy number compared to controls;
      however, common deletion burden was not altered. Complex I deficiency is found in
      SZ brain tissue, and psychotropic medications may play a role in mitochondrial
      dysfunction. Studies of medication-free first-episode psychosis patients are
      needed to elucidate whether mitochondrial pathophysiology occurs independent of
      medication effects.

PMID- 29594136
TI  - Crossing the Worm-Brain Barrier by Using Caenorhabditis elegans to Explore
      Fundamentals of Human Psychiatric Illness.
AB  - Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to
      deconvolute psychiatric illnesses into fundamental symptom clusters or biological
      markers more closely linked to genetic influences. By taking this one step
      farther, these biomarkers can be reduced to protophenotypes - endophenotypes
      conserved during evolution - with counterparts in lower organisms including
      Caenorhabditis elegans and Drosophila. Striking conservation in C. elegans of
      genes that increase the risk for mental illness bolsters the relevance of this
      model system for psychiatric research. Here, I review the characterization of
      several protophenotypes that are relevant for asociality, avolition/anhedonia,
      prepulse inhibition, and anorexia. Interestingly, the analogous behavioral
      defects in C. elegans are also corrected by psychotropic drugs used to treat the
      corresponding symptoms in man and/or are mediated by the same neurotransmitters.
      Overall, there is much we can learn about the complex human brain by studying
      simpler nervous systems directing evolutionarily conserved behaviors. The
      potential for generating important new insights from model organisms appears
      limitless when we begin to recognize the vestiges of evolution in ourselves.

PMID- 29594137
TI  - Artificial Intelligence for the Artificial Kidney: Pointers to the Future of a
      Personalized Hemodialysis Therapy.
AB  - Background: Current dialysis devices are not able to react when unexpected
      changes occur during dialysis treatment or to learn about experience for therapy
      personalization. Furthermore, great efforts are dedicated to develop miniaturized
      artificial kidneys to achieve a continuous and personalized dialysis therapy, in
      order to improve the patient's quality of life. These innovative dialysis devices
      will require a real-time monitoring of equipment alarms, dialysis parameters, and
      patient-related data to ensure patient safety and to allow instantaneous changes
      of the dialysis prescription for the assessment of their adequacy. The analysis
      and evaluation of the resulting large-scale data sets enters the realm of "big
      data" and will require real-time predictive models. These may come from the
      fields of machine learning and computational intelligence, both included in
      artificial intelligence, a branch of engineering involved with the creation of
      devices that simulate intelligent behavior. The incorporation of artificial
      intelligence should provide a fully new approach to data analysis, enabling
      future advances in personalized dialysis therapies. With the purpose to learn
      about the present and potential future impact on medicine from experts in
      artificial intelligence and machine learning, a scientific meeting was organized
      in the Hospital Universitari Bellvitge (L'Hospitalet, Barcelona). As an outcome
      of that meeting, the aim of this review is to investigate artificial intel
      ligence experiences on dialysis, with a focus on potential barriers, challenges,
      and prospects for future applications of these technologies. Summary and Key
      Messages: Artificial intelligence research on dialysis is still in an early
      stage, and the main challenge relies on interpretability and/or comprehensibility
      of data models when applied to decision making. Artificial neural networks and
      medical decision support systems have been used to make predictions about anemia,
      total body water, or intradialysis hypotension and are promising approaches for
      the prescription and monitoring of hemodialysis therapy. Current dialysis
      machines are continuously improving due to innovative technological developments,
      but patient safety is still a key challenge. Real-time monitoring systems,
      coupled with automatic instantaneous biofeedback, will allow changing dialysis
      prescriptions continuously. The integration of vital sign monitoring with
      dialysis parameters will produce large data sets that will require the use of
      data analysis techniques, possibly from the area of machine learning, in order to
      make better decisions and increase the safety of patients.

PMID- 29594138
TI  - Changes in the Spectrum of Kidney Diseases: An Analysis of 40,759 Biopsy-Proven
      Cases from 2003 to 2014 in China.
AB  - Objectives: To evaluate the changing spectrum of kidney diseases over time in
      China using renal biopsy-proven cases. Methods: All patients over the age of 14
      years who were diagnosed with a kidney disease by renal biopsy in the Renal
      Biopsy Registry of the National Clinical Research Center of Kidney Diseases in
      Jinling Hospital, Nanjing, from 2003 to 2014 were included. Results: In total,
      40,759 cases of renal biopsy were analyzed. The mean age of the patients was
      36.59 +/- 14.12 years. 52.0$ of the patients were male. Primary
      glomerulonephritis (PGN), secondary glomerulonephritis, tubulointerstitial
      disease, and hereditary renal diseases accounted for 67.1, 26.4, 2.9, and 2.5$,
      respectively. IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change
      disease, and focal segmental glomerulosclerosis were the leading PGN diagnoses.
      The frequency of MN increased significantly (p < 0.001) by doubling from 2003 to
      2014. An analysis by age category indicated that the frequency of MN increased
      significantly over time (p < 0.001) in all age categories and increased by more
      than 2 times in the 14-24 age category. Lupus nephritis (LN) and Henoch-Schonlein
      purpura nephritis (HSPN) decreased significantly (p < 0.001), diabetic
      nephropathy (DN) increased nearly twice (p < 0.001), monoclonal immunoglobulin
      deposition disease (MIDD) tripled (p < 0.001), and hypertensive nephropathy (HT)
      (p < 0.001) and renal amyloidosis (AMY) (p < 0.05) showed an upward trend. An
      analysis by age category showed that hepatitis B-related nephritis has
      significantly decreased in the 14-24 age category (p < 0.001). Conclusion: PGN
      continued to be the predominant kidney disease in China with IgAN being the most
      common PGN. The frequency of MN increased significantly, with a maximum increase
      in young adults. LN and HSPN decreased significantly, DN and MIDD increased
      significantly, and HT and AMY also showed an increasing trend. The kidney disease
      trends presented in this study serve as a reference point for patient care,
      disease prevention, and public health interventions.

PMID- 29594139
TI  - The Relationship of Residual Renal Function with Cardiovascular Morbidity in
      Hemodialysis Patients and the Potential Role of Monocyte Chemoattractant Protein
      1.
AB  - Background: Residual renal function (RRF) provides several benefits to patients
      on dialysis. Monocyte chemoattractant protein-1 (MCP-1) plays an important role
      in atherosclerotic lesions. We considered the relationship between RRF and
      cardiovascular morbidity and the significant role of MCP-1 serum concentrations
      in hemodiafiltration (HDF) patients. Methods: We enrolled 76 patients on on-line
      HDF. RRF was defined by interdialytic urine output, and we studied the patients
      in two groups according to the preservation or not of urine output. MCP-1 levels
      were measured using enzyme-linked immunosorbent assay. chi2 tests were applied
      for the association between RRF and left ventricular hypertrophy (LVH), coronary
      artery disease (CAD), peripheral artery disease (PAD), and systolic and diastolic
      cardiac dysfunction. We built an adjusted model using logistic regression
      analysis for the factors which might impact on the loss of urine output. Results:
      chi2 tests showed a significant association between the loss of urine output and
      LVH, diastolic dysfunction, and PAD (chi2 = 7.4, p = 0.007; chi2 = 14.3, p =
      0.001; chi2 = 4.2, p = 0.03, respectively), although the association with CAD and
      systolic dysfunction was found to be nonsignificant. The patients without RRF had
      significantly higher MCP-1, and the urine volume was inversely associated with
      MCP-1 (r = -465, p = 0.03). In the built adjusted model, the elevated MCP-1 was
      found to be a significant predictor for the loss of RRF. Conclusion: The loss of
      RRF was significantly associated with LVH, diastolic dysfunction, and PAD in HDF
      patients. The increased MCP-1, affected by the lack of urine, may act as an
      additional underlying factor on this relationship, reflecting a progressive
      inflammation/oxidative stress condition.

PMID- 29594140
TI  - TREM-1 Contributes to Inflammation in IgA Nephropathy.
AB  - Background: Circulating IgA1-containing immune complexes (cIgA1) were shown to
      play important roles in IgA nephropathy (IgAN). They could induce the release of
      multiple inflammatory factors, including MCP-1 and IL-6, and elevated urinary
      inflammatory factors were also reported in patients with IgAN, which suggested
      that inflammation is a major contributor to kidney injury in IgAN. After the
      previous identification of the upregulated release of soluble triggering receptor
      expressed on myeloid cells-1 (sTREM-1) by mesangial cells under cIgA1 challenge
      using cytokine array, in the present study, we further explored the role of TREM
      1, an amplifier of inflammation, in cIgA1-induced kidney injury. Methods: In
      total, 35 patients with IgAN and 17 healthy controls were enrolled. The cIgA1 was
      isolated from plasma and used to treat cultured mesangial cells. The mRNA
      expression of TREM-1 as well as levels of sTREM-1, MCP-1, and IL-6 in the
      mesangial cell supernatant and urine samples were detected. Results: We found
      that cIgA1 from patients with IgAN could significantly upregulate the expression
      of TREM-1 in mesangial cells compared to healthy controls. The levels of
      DeltasTREM-1 were positively correlated with MCP-1 levels in the mesangial
      supernatant. Similarly, higher urinary levels of sTREM-1 were also observed in
      patients with IgAN compared to healthy controls. Moreover, IgAN patients with
      detectable urinary sTREM-1 presented with severe clinical and pathological
      manifestations, including higher IgA and lower eGFR levels, compared to patients
      whose urinary sTREM-1 levels were below the limit of quantification. Conclusion:
      Our present study suggested that TREM-1 in cIgA1 induced inflammatory kidney
      injury in IgAN.

PMID- 29594142
TI  - Rare Bacteria Infecting the Heart and Affecting the Kidney of a Young Child.
AB  - Rare bacteria can lead to infective endocarditis, which may lead to renal
      involvement as severe glomerulonephritis. We report our experience of a 12-year
      old child who presented with infective endocarditis and blood culture-grown
      Gemella morbillorum - a rarely reported bacteria. The clinical picture was
      further complicated with severe glomerulonephritis. Renal biopsy was suggestive
      of crescentic glomerulonephritis. The child was managed with antibiotics,
      steroids, and plasmapheresis and responded well to the treatment. To our
      knowledge, this is the first report of G. morbillorum endocarditis with immune
      complex deposition and necrotizing glomerulonephritis in a child.

PMID- 29594141
TI  - What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered
      and Answers Unquestioned: Reflection on World Kidney Day and International
      Women's Day.
AB  - Chronic kidney disease affects approximately 10$ of the world's adult population:
      it is within the top 20 causes of death worldwide, and its impact on patients and
      their families can be devastating. World Kidney Day and International Women's Day
      in 2018 coincide, thus offering an opportunity to reflect on the importance of
      women's health and specifically their kidney health, on the community and the
      next generations, as well as to strive to be more curious about the unique
      aspects of kidney disease in women so that we may apply those learnings more
      broadly. Girls and women, who make up approximately 50$ of the world's
      population, are important contributors to society and their families. Gender
      differences continue to exist around the world in access to education, medical
      care, and participation in clinical studies. Pregnancy is a unique state for
      women, offering an opportunity for diagnosis of kidney disease, but also a state
      where acute and chronic kidney diseases may manifest, and which may impact future
      generations with respect to kidney health. There are various autoimmune and other
      conditions that are more likely to have an impact on women, with profound
      consequences for child bearing, and on the fetus. Women have different
      complications on dialysis than men, and are more likely to be donors than
      recipients of kidney transplants. In this editorial, we focus on what we do and
      do not know about women, kidney health, and kidney disease, and what we might
      learn in the future to improve outcomes worldwide.

PMID- 29594143
TI  - A Case of Crescentic Glomerulonephritis Complicated with Hypocomplementemic
      Urticarial Vasculitis Syndrome and ANCA-Associated Vasculitis.
AB  - Systemic urticaria in a 64-year-old woman was diagnosed as leukocytoclastic
      vasculitis by a punch biopsy of the skin. Her physical findings improved after
      prescription of prednisolone at a dose of 20 mg/day, but the skin rash relapsed
      with renal dysfunction, proteinuria, and hematuria when the dose of prednisolone
      was reduced over a period of 9 months to 1 mg/day. She was admitted to our
      institute for further examination, when urinary protein and plasma creatinine
      levels were 0.8 g/day and 1.7 mg/dL, respectively. Complement analysis showed
      that levels of total hemolytic component, component C3 fraction, and component C4
      fraction were 30~60% of normal values and the titer of anti-neutrophil
      cytoplasmic antibody for myeloperoxidase (MPO-ANCA) was 89 EU (normal range, <10
      EU), though there were no immunologic disorders such as systemic lupus
      erythematosus. Cellular crescentic glomerulonephritis was observed by light
      microscopy, and immunofluorescent studies showed positive staining for IgG, IgM,
      C3, C4, and C1q. Electron microscopy showed mesangial and subendothelial deposits
      with circumferential mesangial interposition. She fulfilled the diagnostic
      criteria for hypocomplementemic urticarial vasculitis syndrome (HUV), and ANCA
      associated vasculitis (AAV) was also indicated by small vessel vasculitis and
      positive MPO-ANCA. Steroid pulse therapy with methylprednisolone followed by oral
      prednisolone improved her general condition and hypocomplementemia, and MPO-ANCA
      became negative. HUV and AAV are distinct clinical disorders, though both affect
      small blood vessels. Here we report a case of AAV-complicated HUV with crescentic
      glomerulonephritis.

PMID- 29594144
TI  - An Unexpected Case of Scurvy in a Peritoneal Dialysis Patient.
AB  - This case describes an obese adult male peritoneal dialysis patient who presented
      with a pruritic follicular rash. Nutrient deficiency was not suspected initially
      in this case because there was no history of protein-calorie malnutrition, but
      the patient reported a diet devoid of fruits and vegetables and had not been
      taking his dialysis vitamin as prescribed. Skin biopsy showed follicular
      hyperkeratosis with fragmented hair shafts and corkscrew hairs consistent with
      scurvy. After supplementation with ascorbic acid 500 mg twice daily for 2 weeks,
      the rash resolved completely. Dialysis patients are at increased risk for vitamin
      C deficiency due to indiscriminant clearance of the nutrient with dialysis, but
      scurvy is rarely seen.

PMID- 29594145
TI  - Exit Site Infection due to Mycobacterium chelonae in an Elderly Patient on
      Peritoneal Dialysis.
AB  - Nontuberculous mycobacteria (NTM) are rarely isolated from peritoneal dialysis
      (PD)-associated catheter infections. However, NTM infection is usually difficult
      to treat and leads to catheter loss. Prompt diagnosis is essential for
      appropriate treatment. A 70-year-old Japanese man who had been on PD for 2 years
      and with a medical history of 2 episodes of exit site infections (ESIs) due to
      methicillin-resistant Staphylococcus aureus was admitted to the hospital due to
      suspected ESI recurrence. However, Gram staining of the pus revealed no gram
      positive cocci. Instead, weakly stained gram-positive rods were observed after 7
      days of incubation, which were also positive for acid-fast staining. Rapidly
      growing NTM Mycobacterium chelonae was isolated on day 14. Despite administering
      a combination antibiotic therapy, ESI could not be controlled, and catheter
      removal surgery was performed on day 21. Although PD was discontinued
      temporarily, the patient did not require hemodialysis, without any uremic
      symptoms. The catheter was reinserted on day 48, and PD was reinitiated on day
      61. The patient was discharged on day 65. Antibiotic therapy was continued for 3
      months after discharge, with no indications of recurrent infections observed. It
      is important to consider the risk of NTM infections in patients on PD. Acid-fast
      staining could be a key test for prompt diagnosis and provision of an appropriate
      treatment.

PMID- 29594146
TI  - Early Conversion from Tacrolimus to Belatacept in a Highly Sensitized Renal
      Allograft Recipient with Calcineurin Inhibitor-Induced de novo Post-Transplant
      Hemolytic Uremic Syndrome.
AB  - Background: Kidney transplantation is the first-line therapy for patients with
      end-stage renal disease since it offers greater long-term survival and improved
      quality of life when compared to dialysis. The advent of calcineurin inhibitor
      (CNI)-based maintenance immunosuppression has led to a clinically significant
      decline in the rate of acute rejection and better short-term graft survival
      rates. However, these gains have not translated into improvement in long-term
      graft survival. CNI-related nephrotoxicity and metabolic side effects are thought
      to be partly responsible for this. Case Presentation: Here, we report the
      conversion of a highly sensitized renal transplant recipient with pretransplant
      donor-specific antibodies from tacrolimus to belatacept within 1 week of
      transplantation. This substitution was necessitated by the diagnosis of CNI
      induced de novo post-transplant hemolytic uremic syndrome. Conclusion: Belatacept
      is a novel costimulation blocker that is devoid of the nephrotoxic properties of
      CNIs and has been shown to positively impact long-term graft survival and
      preserve renal allograft function in low-immunologic-risk kidney transplant
      recipients. Data regarding its use in patients who are broadly sensitized to
      human leukocyte antigens are scarce, and the increased risk of rejection
      associated with belatacept has been a deterrent to more widespread use of this
      immunosuppressive agent. This case serves as an example of a highly sensitized
      patient that has been successfully converted to a belatacept-based CNI-free
      regimen.

PMID- 29594147
TI  - Oxcarbazepine Therapy for Complete Central Diabetes Insipidus.
AB  - Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We
      describe a patient with complete central diabetes insipidus and seizures who
      developed worsening hyponatremia when her dose of oxcarbazepine was increased.
      The patient maintained a normal serum sodium level and has had appropriately
      concentrated urine for 5 years on just oxcarbazepine, despite undetectable
      antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of
      its metabolites) may stimulate collecting tubule V2 receptor-G protein complex
      independent of ADH, resulting in increased renal tubular water reabsorption.
      Oxcarbazepine may be useful as an alternative therapy for patients with central
      diabetes insipidus.

PMID- 29594148
TI  - C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important
      Manifestations of Complement System Dysfunction.
AB  - The advances in our understanding of the alternative pathway have emphasized that
      uncontrolled hyperactivity of this pathway causes 2 distinct disorders that
      adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome
      (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target
      organ injury to multiple organs, most commonly the kidney. On the other hand, in
      the so-termed C3 glomerulopathy, kidney involvement is not associated with
      thrombocytopenia, anemia, or other system involvement. In this report, we present
      2 cases of alternative pathway dysfunction. The 60-year-old female patient had
      biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was
      diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and
      normal ADAMTS-13 level. The aHUS patient was successfully treated with the
      monoclonal antibody (eculizumab) for complement blockade. The patient with C3
      glomerulopathy did not receive the monoclonal antibody. In this patient,
      management focused on blood pressure and proteinuria control with an angiotensin
      converting enzyme inhibitor. This article focuses on the clinical differences,
      pathophysiology, and treatment of aHUS and C3 glomerulopathy.

PMID- 29594149
TI  - Temporal Dynamics of Gene Expression During Endothelial Cell Differentiation From
      Human iPS Cells: A Comparison Study of Signalling Factors and Small Molecules.
AB  - Endothelial cell (EC) therapy may promote vascular growth or reendothelization in
      a variety of disease conditions. However, the production of a cell therapy
      preparation containing differentiated, dividing cells presenting typical EC
      phenotype, functional properties and chemokine profile is challenging. We focused
      on comparative analysis of seven small molecule-mediated differentiation
      protocols of ECs from human induced pluripotent stem cells. Differentiated cells
      showed a typical surface antigen pattern of ECs as characterized with flow
      cytometry analysis, functional properties, such as tube formation and ability to
      uptake acetylated LDL. Gene expression analysis by RNA sequencing revealed an
      efficient silencing of pluripotency genes and upregulation of genes related to
      cellular adhesion during differentiation. In addition, distinct patterns of
      transcription factor expression were identified during cellular reprogramming
      providing targets for more effective differentiation protocols in the future.
      Altogether, our results suggest that the most optimal EC differentiation protocol
      includes early inhibition of Rho-associated coiled-coil kinase and activation of
      cyclic AMP signaling, and inhibition of transforming growth factor beta signaling
      after mesodermal stage. These findings provide the first systematic
      characterization of the most potent signalling factors and small molecules used
      to generate ECs from human induced pluripotent stem cells and, consequently, this
      work improves the existing EC differentiation protocols and opens up new avenues
      for controlling cell fate for regenerative EC therapy.

PMID- 29594150
TI  - Mechanotransduction in Coronary Vein Graft Disease.
AB  - Autologous saphenous veins are the most commonly used conduits in
      revascularization of the ischemic heart by coronary artery bypass graft surgery,
      but are subject to vein graft failure. The current mini review aims to provide an
      overview of the role of mechanotransduction signalling underlying vein graft
      failure to further our understanding of the disease progression and to improve
      future clinical treatment. Firstly, limitation of damage during vein harvest and
      engraftment can improve outcome. In addition, cell cycle inhibition, stimulation
      of Nur77 and external grafting could form interesting therapeutic options.
      Moreover, the Hippo pathway, with the YAP/TAZ complex as the main effector, is
      emerging as an important node controlling conversion of mechanical signals into
      cellular responses. This includes endothelial cell inflammation, smooth muscle
      cell proliferation/migration, and monocyte attachment/infiltration. The combined
      effects of expression levels and nuclear/cytoplasmic translocation make YAP/TAZ
      interesting novel targets in the prevention and treatment of vein graft disease.
      Pharmacological, molecular and/or mechanical conditioning of saphenous vein
      segments between harvest and grafting may potentiate targeted and specific
      treatment to improve long-term outcome.

PMID- 29594151
TI  - Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel
      Molecular Therapeutic Targets.
AB  - Calcific Aortic Valve Disease (CAVD) is the most common heart valve disease and
      its incidence is expected to rise with aging population. No medical treatment so
      far has shown slowing progression of CAVD progression. Surgery remains to this
      day the only way to treat it. Effective drug therapy can only be achieved through
      a better insight into the pathogenic mechanisms underlying CAVD. The cellular and
      molecular events leading to leaflets calcification are complex. Upon endothelium
      cell damage, oxidized LDLs trigger a proinflammatory response disrupting healthy
      cross-talk between valve endothelial and interstitial cells. Therefore, valve
      interstitial cells transform into osteoblasts and mineralize the leaflets.
      Studies have investigated signaling pathways driving and connecting lipid
      metabolism, inflammation and osteogenesis. This review draws a summary of the
      recent advances and discusses their exploitation as promising therapeutic targets
      to treat CAVD and reduce valve replacement.

PMID- 29594152
TI  - Ionizing Radiation Induces Endothelial Inflammation and Apoptosis via p90RSK
      Mediated ERK5 S496 Phosphorylation.
AB  - Adverse cardiovascular events are a leading nonmalignant cause of morbidity and
      mortality among cancer survivors who have been exposed to ionizing radiation
      (IR), but the exact mechanism of the cardiovascular complications induced by IR
      remains unclear. In this study we investigated the potential role of the p90RSK
      ERK5 module in regulating IR-induced endothelial cell inflammation and apoptosis.
      Whole body radiation of mice with 2 Gy gamma-ray significantly increased
      endothelial VCAM-1 expression; especially in the disturbed flow area in vivo. In
      vitro studies showed that IR increased p90RSK activation as well as subsequent
      ERK5 S496 phosphorylation in cultured human endothelial cells (ECs). A specific
      p90RSK inhibitor, FMK-MEA, significantly inhibited both p90RSK activation and
      ERK5 S496 phosphorylation, but it had no effect on IR-induced ERK5 TEY motif
      phosphorylation, suggesting that p90RSK regulates ERK5 transcriptional activity,
      but not its kinase activity. In fact, we found that IR-induced NF-kB activation
      and VCAM-1 expression in ECs were significantly inhibited by the over-expression
      of S496 phosphorylation site mutant of ERK5 (ERK5 S496A) compared to
      overexpression of wild type ERK5. Furthermore, when ECs were exposed to IR, the
      number of annexin V positive cells increased, and overexpression of ERK5 S496A,
      but not wild type ERK5, significantly inhibited this increase. Our results
      demonstrate that IR augmented disturbed flow-induced VCAM-1 expression in vivo.
      Endothelial p90RSK was robustly activated by IR and subsequently up-regulated
      ERK5 S496 phosphorylation, inflammation, and apoptosis in ECs. The EC p90RSK-ERK5
      signaling axis can be a good target to prevent cardiovascular events after
      radiation therapy in cancer patients.

PMID- 29594153
TI  - Evaluation of 25% Poloxamer As a Slow Release Carrier for Morphine in a Rat
      Model.
AB  - The objectives of this study were to evaluate poloxamer as a slow release carrier
      for morphine (M) and potential tissue irritation after subcutaneous poloxamer
      morphine (PM) injection in a rat model. Based on the result of a previous in
      vitro work, 25% poloxamer, with and without morphine, and saline were
      administered in 14 rats' flanks. Blood for morphine concentrations was
      automatically sampled at multiple preprogrammed time points using the CulexTM
      unit for 48 h. Skin tissues from the injection sites were harvested and evaluated
      for histopathological changes. Following M or PM administration, it was
      determined that the half-life (t1/2) was significantly longer in the PM (5.5 +/-
      7.2 h) than M (0.7 +/- 0.8 h) indicated a slow dissolution of poloxamer with
      morphine. The tmax was within 15 min and Cmax was approximately three times
      higher with M than with PM, reaching 716.8 (+/-153.7 ng/ml) of plasma morphine
      concentrations. There was no significant difference in total area under the curve
      and clearance of M versus PM. Histology inflammatory scores were similar between
      M, PM, and poloxamer but were significantly higher than saline control. We
      concluded that 25% poloxamer was capable of increasing the t1/2 of morphine,
      without a significant tissue irritation.

PMID- 29594154
TI  - A Systems Approach to Evaluate One Health Initiatives.
AB  - Challenges calling for integrated approaches to health, such as the One Health
      (OH) approach, typically arise from the intertwined spheres of humans, animals,
      and ecosystems constituting their environment. Initiatives addressing such wicked
      problems commonly consist of complex structures and dynamics. As a result of the
      EU COST Action (TD 1404) "Network for Evaluation of One Health" (NEOH), we
      propose an evaluation framework anchored in systems theory to address the
      intrinsic complexity of OH initiatives and regard them as subsystems of the
      context within which they operate. Typically, they intend to influence a system
      with a view to improve human, animal, and environmental health. The NEOH
      evaluation framework consists of four overarching elements, namely: (1) the
      definition of the initiative and its context, (2) the description of the theory
      of change with an assessment of expected and unexpected outcomes, (3) the process
      evaluation of operational and supporting infrastructures (the "OH-ness"), and (4)
      an assessment of the association(s) between the process evaluation and the
      outcomes produced. It relies on a mixed methods approach by combining a
      descriptive and qualitative assessment with a semi-quantitative scoring for the
      evaluation of the degree and structural balance of "OH-ness" (summarised in an OH
      index and OH-ratio, respectively) and conventional metrics for different outcomes
      in a multi-criteria-decision-analysis. Here, we focus on the methodology for
      Elements (1) and (3) including ready-to-use Microsoft Excel spreadsheets for the
      assessment of the "OH-ness". We also provide an overview of Element (2), and
      refer to the NEOH handbook for further details, also regarding Element (4)
      (http://neoh.onehealthglobal.net). The presented approach helps researchers,
      practitioners, and evaluators to conceptualise and conduct evaluations of
      integrated approaches to health and facilitates comparison and learning across
      different OH activities thereby facilitating decisions on resource allocation.
      The application of the framework has been described in eight case studies in the
      same Frontiers research topic and provides first data on OH-index and OH-ratio,
      which is an important step towards their validation and the creation of a dataset
      for future benchmarking, and to demonstrate under which circumstances OH
      initiatives provide added value compared to disciplinary or conventional health
      initiatives.

PMID- 29594155
TI  - Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In
      Vitro.
AB  - Equine herpesvirus type 1 (EHV-1) is a ubiquitous and highly contagious pathogen
      that causes a range of disease severities with outbreaks of notable economic
      impact. Given the limitations in immune protection of current vaccines and the
      limited effectiveness of antiviral drugs on EHV-1 infections in vivo, improved
      treatment measures are needed to control disease. The use of drugs that alter the
      epigenetic state of herpes simplex virus genome has been shown to limit viral
      primary infection and reactivation both in vitro and in vivo. Therefore, we
      tested the hypothesis that maintaining a repressive epigenetic state on the EHV-1
      genome in the host equine cell would decrease viral load during lytic infection.
      Equine fetal kidney cells (EFKCs) or isolated peripheral blood leukocytes were
      treated in vitro with (a) the nucleoside analog ganciclovir; (b) the histone
      demethylase inhibitor OG-L002; (c) both ganciclovir and OG-L002; or (d) dimethyl
      sulfoxide (DMSO, vehicle control); and then infected with a clinical EHV-1
      isolate. Treatment of EFKCs with ganciclovir (mean 22.3 DNA copies per cell, p =
      0.0005), OG-L002 (mean 25.6, p = 0.005) or both ganciclovir and OG-L002 (mean
      7.1, p = 0.0001) resulted in decreased EHV-1 viral load at 24 h post-infection
      (hpi) in comparison with DMSO (mean 42.0), with greater impact using the combined
      treatment. Further, EHV-1 gene expression at 3 hpi decreased when EFKCs were
      infected in the presence of ganciclovir (p = 0.04) and combined treatment of
      ganciclovir and OG-L002 (p = 0.0003). In contrast, under similar conditions,
      neither ganciclovir nor OG-L002 suppressed EHV-1 infection in leukocytes.
      Differences between cell types, drug penetrance, or drug turnover, may have
      contributed to the distinct effects observed in this study.

PMID- 29594156
TI  - Affectionate Interactions of Cats with Children Having Autism Spectrum Disorder.
AB  - Mental and physical benefits of dogs have been reported for adults and children
      with special needs, but less is known about benefits of cats for children. A cat
      that can be held by a child could provide important therapeutic companionship for
      children with severe or less severe autism spectrum disorder (ASD) who otherwise
      may lack prosocial behaviors. Because relatively little is known about the
      behavior of cats around children, we conducted this study. Phase 1 gathered web
      survey data from families having an adult cat and a child with ASD (n = 64). In
      Phase 2, there were direct telephone interviews of parents having a child with
      severe ASD (n = 16) or less severe ASD (n = 11), or typical development (n = 17).
      From the Phase 1 web survey of families with ASD children (full range of
      severities), affectionate interactions of the cats with children were common.
      Most parents with ASD children volunteered positive comments regarding the cat,
      such as calming the child, being a soothing protector or a guardian. In the
      interviews in Phase 2, for all three groups, most parents characterized cats as
      at least moderately affectionate toward the child. However, cats living with
      severe ASD children were reported to exhibit less affection than those living
      with typically developing children or children with less severe ASD. A minority
      of cats in each group showed some aggression to the specified child; this was not
      elevated with ASD children. Responses suggested that the cats adopted as kittens
      were more affectionate and less aggressive to all categories of children than
      those adopted as adults. Overall, participants reported that ASD children's
      behaviors indicated that they valued the relationship with the cat, similar to
      typically developing children, pointing to the importance and potential
      usefulness of selecting affectionate and compatible cats for ASD children.

PMID- 29594157
TI  - Use of Nasotracheal Intubation during General Anesthesia in Two Ponies with
      Tracheal Collapse.
AB  - Ponies with tracheal collapse may have an increased anesthetic risk due to airway
      obstruction during induction and recovery. To our knowledge, there are no
      anesthetic descriptions of these patients, despite a reported 5.6% incidence and
      77% mortality rate. Two Shetland ponies with tracheal collapse, a 12-year-old
      male (pony 1) and a 27-year-old female (pony 2), were referred for right eye
      enucleation due to a perforating corneal ulcer and severe recurrent uveitis,
      respectively. Pony 1 was stressed, had lung stridor and hyperthermia, and
      developed inspiratory dyspnea with handling. Radiography confirmed collapse of
      the entire trachea as well as inflammation of the lower airways. Corticosteroids
      and bronchodilators were administered by nebulization for 1 week before surgery.
      Pony 2 had a grade III/VI mitral murmur and a clinical history of esophageal
      obstructions and tracheal collapse requiring tracheostomy. Both ponies were
      premedicated with acepromazine and xylazine; anesthesia was induced with
      midazolam and ketamine. Nasotracheal intubation was performed in left lateral
      recumbency with extension of the neck and head and was guided by capnography. The
      nasotracheal tube consisted of two endotracheal tubes attached end-to-end to
      create a tube of adequate length and diameter. Pony 2 was orotracheally intubated
      during surgery and later reintubated with a nasotracheal tube. Anesthesia was
      maintained with isoflurane using volume-controlled ventilation. Analgesia was
      provided by a retrobulbar blockade with mepivacaine and lidocaine. Cardiovascular
      support consisted of lactated Ringer's solution and dobutamine. After surgery,
      the ponies were administered xylazine and supplemented with oxygen through the
      nasotracheal tube. Recovery was assisted by manual support of the head and tail.
      Successful extubation was achieved following butorphanol administration after
      approximately 1 h in standing position. Both ponies were discharged from the
      clinic a few days after surgery.

PMID- 29594159
TI  - Prepartum Maternal Behavior of Domesticated Cattle: A Comparison with Managed,
      Feral, and Wild Ungulates.
AB  - The event of giving birth is an essential part of animal production. In dairy
      cattle production, there are substantial economical and welfare-related
      challenges arising around the time of parturition, and hence increased focus on
      efficient management of the calving cow. Drawing on the research literature on
      prepartum maternal behavior, this review compares cattle to other members of the
      ungulate clade with the aim of understanding the biological basis of bovine
      prepartum behavior with main emphasis on dairy cows. Ultimately, this knowledge
      may be used in future development of housing systems and recommendations for the
      management of calving cows. Maternal prepartum behavior varies among species, but
      the final goal of ungulate mothers is the same: ensuring a calm parturition and
      optimal environment for the onset of postpartum maternal behavior by locating an
      appropriate birth site, with low risk of predators, disturbances and mistaken
      identity of offspring. Features of chosen birth sites vary among species and
      depend largely on the environment, as ungulate females display a considerable
      ability to adapt to their surroundings. However, within commercial housing
      conditions in dairy production, the animals' ability to adapt behaviorally
      appears to be challenged. Confinement alongside high stocking densities leave
      little room to express birth-site selection behavior, posing a high risk of
      agonistic social behavior, disturbances, and mismothering, as well as exposure to
      olfactory cues influencing both prepartum and postpartum maternal behavior. Dairy
      cows are thus exposed to several factors in a commercial calving environment,
      which may thwart their maternal motivations and influence their behavior. In
      addition, prepartum cattle may be more affected by olfactory cues than other
      ungulate species (e.g., sheep) because they are attracted to birth fluids already
      before calving. Hence, providing dairy cows with an environment where they can
      perform the maternal behavior they are motivated for, may aid a calm and secure
      calving and provide optimal surroundings for postpartum maternal behavior. Future
      research should focus on designing motivation-based housing systems allowing
      freedom to express prepartum maternal behavior and investigate in more detail the
      effects of the environment on the welfare of calving cows and their offspring.

PMID- 29594158
TI  - Effect of Melatonin Implants during the Non-Breeding Season on the Onset of
      Ovarian Activity and the Plasma Prolactin in Dromedary Camel.
AB  - To examine a possible control of reproductive seasonality by melatonin, continual
      release subcutaneous melatonin implants were inserted 4.5 months before the
      natural breeding season (October-April) into female camels (Melatonin-treated
      group). The animals were exposed to an artificial long photoperiod (16L:8D) for
      41 days prior to implant placement to facilitate receptivity to the short-day
      signal that is expected with melatonin implants. The treated and control groups
      (untreated females) were maintained separately under outdoor natural conditions.
      Ovarian follicular development was monitored in both groups by transrectal
      ultrasonography and by plasma estradiol-17beta concentrations performed weekly
      for 8 weeks and then for 14 weeks following implant insertion. Plasma prolactin
      concentrations were determined at 45 and 15 days before and 0, 14, 28, 56, and 98
      days after implant insertion. Plasma melatonin concentration was determined to
      validate response to the artificial long photoperiod and to verify the pattern of
      release from the implants. Results showed that the artificial long photoperiod
      induced a melatonin secretion peak of significantly (P < 0.05) shorter duration
      (about 2.5 h). Melatonin release from the implants resulted in higher circulating
      plasma melatonin levels during daytime and nighttime which persisted for more
      than 12 weeks following implants insertion. Treatment with melatonin implants
      advanced the onset of follicular growth activity by 3.5 months compared to
      untreated animals. Plasma estradiol-17beta increased gradually from the second
      week after the beginning of treatment to reach significantly (P < 0.01) higher
      concentrations (39.2 +/- 6.2 to 46.4 +/- 4.5 pg/ml) between the third and the
      fifth week post insertion of melatonin implants. Treatment with melatonin
      implants also induced a moderate, but significant (P < 0.05) suppressive effect
      on plasma prolactin concentration on the 28th day. These results demonstrate that
      photoperiod appears to be involved in dromedary reproductive seasonality.
      Melatonin implants may be a useful tool to manipulate seasonality and to improve
      reproductive performance in this species. Administration of subcutaneous
      melatonin implants during the transition period to the breeding season following
      an artificial signal of long photoperiod have the potential to advance the
      breeding season in camels by about 2.5 months.

PMID- 29594160
TI  - Job-Related Stress in Forensic Interviewers of Children with Use of Therapy Dogs
      Compared with Facility Dogs or No Dogs.
AB  - Sexually abused children providing essential testimony regarding crimes in
      forensic interviews now sometimes are provided facility dogs or therapy dogs for
      comfort. Facility dogs are extensively trained to work with forensic
      interviewers; when using therapy dogs in interviews, volunteers are the dog
      handlers. Interviews can impact child welfare workers' mental health causing
      secondary traumatic stress (STS). To investigate this stress, first data were
      gathered on stress retrospectively for when interviewers initially started the
      job prior to working with a dog, and then currently, from forensic interviewers
      using a facility dog, a therapy or pet dog, or no dog. These retrospective and
      secondary traumatic stress scale (STSS) data compared job stress among
      interviewers of children using: a certified, workplace facility dog (n = 16), a
      volunteer's trained therapy dog or the interviewer's pet dog (n = 13/3), or no
      dog (n = 198). Retrospective scores of therapy dog and no dog interviewers'
      stress were highest for the first interviewing year 1 and then declined.
      Extremely or very stressful retrospective scores differed among the three groups
      in year 1 (p < 0.038), and were significantly elevated for the therapy dog group
      as compared with the facility dog group (p < 0.035). All interviewing groups had
      elevated STSS scores; when compared with other healthcare groups that have been
      studied, sub-scores were especially high for Avoidance: a psychological coping
      mechanism to avoid dealing with a stressor. STSS scores differed among groups (p
      < 0.016), primarily due to Avoidance sub-scores (p < 0.009), reflecting higher
      Avoidance scores for therapy dog users than no dog users (p < 0.009). Facility
      dog users more consistently used dogs during interviews and conducted more
      interviews than therapy/pet dog users; both groups favored using dogs.
      Interviewers currently working with therapy dogs accompanied by their volunteers
      reported they had experienced heightened stress when they began their jobs; their
      high stress levels still persisted, indicating lower inherent coping skills and
      perhaps greater empathy among interviewers who later self-selected to work with
      therapy dogs. Results reveal extreme avoidant stress for interviewers witnessing
      children who are suffering and their differing coping approaches.

PMID- 29594161
TI  - Assessing the Economic Impact of Vaccine Availability When Controlling Foot and
      Mouth Disease Outbreaks.
AB  - Predictive models have been used extensively to assess the likely effectiveness
      of vaccination policies as part of control measures in the event of a foot and
      mouth disease (FMD) outbreak. However, the availability of vaccine stocks and the
      impact of vaccine availability on disease control strategies represent a key
      uncertainty when assessing potential control strategies. Using an
      epidemiological, spatially explicit, simulation model in combination with a
      direct cost calculator, we assessed how vaccine availability constraints may
      affect the economic benefit of a "vaccination-to-live" strategy during a FMD
      outbreak in Scotland, when implemented alongside culling of infected premises and
      dangerous contacts. We investigated the impact of vaccine stock size and
      restocking delays on epidemiological and economic outcomes. We also assessed
      delays in the initial decision to vaccinate, maximum daily vaccination capacity,
      and vaccine efficacy. For scenarios with conditions conducive to large outbreaks,
      all vaccination strategies perform better than the strategy where only culling is
      implemented. A stock of 200,000 doses, enough to vaccinate 12% of the Scottish
      cattle population, would be sufficient to maximize the relative benefits of
      vaccination, both epidemiologically and economically. However, this generates a
      wider variation in economic cost than if vaccination is not implemented, making
      outcomes harder to predict. The probability of direct costs exceeding L500
      million is reduced when vaccination is used and is steadily reduced further as
      the size of initial vaccine stock increases. If only a suboptimal quantity of
      vaccine doses is initially available (100,000 doses), restocking delays of more
      than 2 weeks rapidly increase the cost of controlling outbreaks. Impacts of low
      vaccine availability or restocking delays are particularly aggravated by delays
      in the initial decision to vaccinate, or low vaccine efficacy. Our findings
      confirm that implementing an emergency vaccination-to-live strategy in addition
      to the conventional stamping out strategy is economically beneficial in scenarios
      with conditions conducive to large FMD outbreaks in Scotland. However, the size
      of the initial vaccine stock available at the start of the outbreak and the
      interplay with other factors, such as vaccine efficacy and delays in restocking
      or implementing vaccination, should be considered in making decisions about
      optimal control strategies for FMD outbreaks.

PMID- 29594162
TI  - A Proof of Concept: Are Detection Dogs a Useful Tool to Verify Potential
      Biomarkers for Lung Cancer?
AB  - Early and reliable diagnostic test is essential for effective therapy of lung
      cancer. Volatile organic compounds that are characteristic for cancer could serve
      as valuable biomarkers in cancer diagnosis. Both trace analytical and detection
      dog approaches give some evidence for the existence of such biomarkers. In this
      proof of concept, study dogs and trace analysis were implemented in combination
      to gain more information concerning cancer biomarkers. Two dogs were trained to
      distinguish between absorbed breath samples of lung cancer patients and healthy
      persons and succeeded with correct identification of patients with 9/9 and 8/9
      and correct negative indications from of 8/10 and 4/10 samples from healthy
      individuals. A recent observational study found that breath samples from lung
      cancer patients showed an increase in 1-butanol, 2-butanone, 2-pentanone, and
      hexanal. Synthetic air samples were therefore fortified with these compounds and
      adsorbed to a fleece. Tested against breath samples from healthy probands, on
      presentation to the dogs these synthetic samples provoked an indication in three
      out of four samples. We were able to demonstrate that a combination of the
      natural nose of a dog and a trace analytic technique can be a valuable concept in
      the search for cancer biomarkers.

PMID- 29594163
TI  - Augmented Reality, Cyber-Physical Systems and Robotics: Nice to Have or a Program
      with Future?

PMID- 29594164
TI  - Upper Gastrointestinal Surgery: Robotic Surgery versus Laparoscopic Procedures
      for Esophageal Malignancy.
AB  - Background: The evolution of minimally invasive surgery (MIS) also extends to the
      field of esophageal surgery and has brought forth the development of several
      approaches of minimally invasive esophagectomy (MIE). Hybrid and total minimally
      invasive operative techniques have proven beneficial compared to open surgery and
      are currently evaluated against robotic-assisted minimally invasive esophagectomy
      (RAMIE). We aim to review the current literature regarding the position of MIE
      versus RAMIE. Methods: A systematic review of the relevant literature on
      minimally invasive esophageal surgery for cancer is presented. A PubMed search
      was carried out for the period of 1992-2018 with the following search terms:
      'esophageal cancer', 'minimally invasive surgery', 'resection', 'transhiatal',
      'transthoracic', 'MIE', 'hybrid', 'robotic resection', 'RAMIE', 'RATE'. Results:
      Hybrid and total minimally invasive operative techniques have proven beneficial,
      especially with regard to pulmonary complications, compared to open surgery.
      Oncologic outcomes appear equivalent between open and minimally invasive
      techniques. Currently, the position of RAMIE is being evaluated against other
      minimally invasive techniques. Conclusion: All minimally invasive techniques
      confer the expected reduction in perioperative morbidity compared to open
      surgery. However, MIS is still evolving with regard to specific technical
      challenges, especially anastomotic techniques.

PMID- 29594165
TI  - Lower Gastrointestinal Surgery: Robotic Surgery versus Laparoscopic Procedures.
AB  - Introduction: For a long time, the comprehensive application of minimally
      invasive techniques in lower gastrointestinal (GI) surgery was substantially
      impaired by inherent anatomical and technical complexities. Recently, several new
      techniques such as robotic operating platforms and transanal total mesorectal
      excision (taTME) have revolutionized the minimally invasive approach. This review
      aims to depict the current state of the art and evaluates the advantages and
      drawbacks in regard to perioperative outcome and quality of oncological
      resection. Methods: A systematic literature search was performed using the search
      terms 'colorectal cancer', 'rectal cancer', 'minimally invasive surgery',
      'laparoscopic surgery', and 'robotic' to identify relevant studies reporting on
      robotic surgery (RS) either alone or in comparison to laparoscopic surgery (LS).
      Publications on taTME were analyzed separately. Results: 69 studies reporting on
      RS with a total of 20,872 patients, and 17 articles on taTME including 881
      patients, were identified. Conclusion: Both RS and taTME can facilitate a
      minimally invasive approach for lower GI surgery in an increasing number of
      patients. Furthermore, combining both techniques might become an auspicious
      approach in selected patients; further prospective and randomized trials are
      needed to verify its benefits over conventional laTME.

PMID- 29594166
TI  - Robot-Assisted Transplant Surgery - Vision or Reality? A Comprehensive Review.
AB  - Minimally invasive surgery is standard procedure for many operations. Further
      refinements include the introduction of robotic surgery which is still an
      emerging field especially in laparoscopic surgery. Since the successful
      introduction of the da Vinci Robotic Surgical System, the robotic approach in
      organ transplantation has become of great interest in both the live donor organ
      retrieval and the recipient operation. Robotic surgery for kidney, liver, and
      pancreas transplantation is feasible. Over 700 donor nephrectomies and 100 kidney
      transplantations have been performed already, and robotic surgery is standard in
      a small number of pioneer centers; however, larger series and most importantly
      randomized controlled trials for the highest evidence are needed. Longer warm
      ischemia time and higher costs limit these procedures at the moment.

PMID- 29594167
TI  - First Experiences with the New Senhance(r) Telerobotic System in Visceral
      Surgery.
AB  - Until recently, robotic-assisted surgery has exclusively been connected to the
      name DaVinci(r). In 2016, a second robotic system, the Senhance(r), became
      available. To introduce the new robotic system into clinical routine, detailed
      team training and an integration program were useful. Within the first 6 months,
      116 cases were performed with this system. The integration program intended to
      start with simple and well-standardized clinical cases. We chose inguinal hernia
      repair using the TAPP (transabdominal preperitoneal) technique as the starting
      procedure. Subsequently, we added upper gastrointestinal surgery and
      cholecystectomies, and colorectal procedures have since also been included.
      Initial experience with the Senhance system as the first installation in Germany
      shows that it is suitable for surgery in general and for visceral surgery in
      particular. The application is safe due to the unproblematically quick changeover
      to normal laparoscopy and easy to integrate due to the very short system
      integration times (docking times). Since it is a laparoscopic-based system,
      following an integration program will enable experienced laparoscopic surgeons to
      very quickly manage more complex procedures. Due to lower costs, introducing
      robotic surgery starting with simple and standardized procedures is more
      feasible. After the establishment of this second robotic system, future studies
      will have to specifically look at differences in surgical results and basic
      conditions of different robotic-assisted systems. This paper documents the
      decision-making process of a hospital towards the integration of a robotic system
      and the selection criteria used while also demonstrating the planning and
      execution process during the introduction of the system into clinical routine.

PMID- 29594168
TI  - Feasibility and Usefulness of a Joystick-Guided Robotic Scope Holder (Soloassist)
      in Laparoscopic Surgery.
AB  - Introduction: The Soloassist(r) system is a joystick-guided robotic scope holder.
      We evaluated the efficacy of Soloassist in laparoscopic surgery. Methods: We
      investigated operative time, blood loss, set-up time, length of hospital stay,
      and the number of participating surgeons in laparoscopic cholecystectomy cases
      before and after the introduction of Soloassist. Furthermore, we evaluated these
      factors in each group of 20 elective and emergency cholecystectomy cases by
      single surgeon after matching their background. To evaluate the performance level
      of operating Soloassist, we divided the operative field into three areas. Then we
      counted the frequency of energy device activation in initially 10 cases by a
      single surgical resident and observed its change. Results: The number of
      participating surgeons was significantly less and postoperative hospital days
      were fewer in the Soloassist group. There was no significant difference between
      set-up time and blood loss both in elective and emergency cases. The total number
      of energy device activations and that in the dangerous area decreased in
      accordance with the experience. Conclusion: Considering our results and previous
      reports, the combination use of an ideal active scope holder and a commercially
      available 3D scope is currently considered the best approach in laparoscopic
      surgery. In the near future, development of active scope holders might play an
      important role in laparoscopic surgery.

PMID- 29594169
TI  - Robotic Endoscopy.
AB  - Endoscopes extend the eyes of the physician into the patient's body. They are
      widely used in gastrointestinal (GI) diagnostics and minimally invasive surgery.
      Endoscopes can be classified into 3 types: rigid, flexible, and capsule
      endoscopes. Rigid and flexible endoscopes are traditionally held and manipulated
      by the physician to visualize the region of interest, while capsule endoscopes
      move passively along with the GI peristalsis. With the advancement of technology,
      robotic endoscopy has been increasingly developed and accepted. In this work,
      robotic endoscopy from 3 categories (robot-assisted rigid endoscopy, robot
      assisted flexible endoscopy, and active GI endoscopy including active flexible
      colonoscopy and active capsule endoscopy) is reviewed by PubMed search with the
      criteria ('Robotics' OR 'Robot') and ('Endoscopy' OR 'Endoscope').

PMID- 29594171
TI  - Augmented Reality, Cyber-Physical Systems and Robotic Surgery: Nice to Have or a
      Program with Future?

PMID- 29594170
TI  - Enhanced Visualization: From Intraoperative Tissue Differentiation to Augmented
      Reality.
AB  - Background: Optimal visualization of the operative field and methods that
      additionally provide supportive optical information form the basis for target
      directed and successful surgery. This article strives to give an overview of
      current enhanced visualization techniques in visceral surgery and to highlight
      future developments. Methods: The article was written as a comprehensive review
      on this topic and is based on a MEDLINE search and ongoing research from our own
      group and from other working groups. Results: Various techniques for enhanced
      visualization are described comprising augmented reality, unspecific and targeted
      staining methods, and optical modalities such as narrow-band imaging. All
      facilitate our surgical performance; however, due to missing randomized
      controlled studies for most of the innovations reported on, the available
      evidence is low. Conclusion: Many new visualization technologies are emerging
      with the aim to improve our perception of the surgical field leading to less
      invasive, target-oriented, and elegant treatment forms that are of significant
      benefit to our patients.

PMID- 29594172
TI  - Endoscopic Surveillance in Inflammatory Bowel Disease.
AB  - Introduction: Endoscopy is a key technique for the surveillance of patients with
      inflammatory bowel diseases (Crohn's disease (CD) and ulcerative colitis).
      Indication to perform endoscopy for surveillance includes assessment of response
      to therapy, postoperative surveillance, and surveillance for intraepithelial
      neoplasia. Methods: In addition to personal experience, a literature search was
      performed and the guidelines were consulted. Results and Conclusion: Endoscopy is
      the gold standard in the long-term assessment of mucosal healing and in the short
      term control of response to intensified therapy. For postoperative surveillance
      in CD, mucosal changes (as graded by the Rutgeerts score) are predictive of
      clinical recurrence. For neoplasia surveillance, virtual chromoendoscopy has not
      (yet) replaced conventional chromoendoscopy. Surveillance can be optimized by the
      use of high-definition endoscopes as well as (pan-)chromoendoscopy and requires
      time to scrutinize the mucosa. This approach seems to be superior to random
      biopsies.

PMID- 29594173
TI  - Acinar Cell Cystadenoma - a Rarity in Advanced von Hippel-Lindau Disease: A Case
      Report.
AB  - Background: Von Hippel-Lindau (VHL) disease may occur at various localisations
      which can be both intra- and extrapancreatic as well as challenging to diagnose
      by medical imaging. Case Report: A positron emission tomography/magnetic
      resonance imaging in a 40-year-old woman was performed to monitor a
      haemangioblastoma. Additionally, it showed findings which were considered to be a
      pancreatic neuroendocrine tumour (pNET) and retroumbilical metastasis. The
      suspected metastasis was laparoscopically resected; however, pathological
      evaluation did not lead to a clear categorisation. Consequently, the pancreatic
      head was resected in which a pNET and various acinar cell cystadenomas were
      found. Conclusion: Diagnostic and therapy of advanced VHL disease can be
      difficult; if in doubt, a surgical approach may establish clarity.

PMID- 29594174
TI  - Relationship between areas of cognitive functioning on the Mini-Mental State
      Examination and crash risk.
AB  - Previous studies have suggested that the pattern of cognitive impairment in crash
      involved older drivers is different from non-crash involved older drivers. This
      study assessed the relationship between seven areas of cognitive functioning
      (orientation to time, orientation to place, registration, attention and
      calculation, recall, language, and visual construction) on the Mini-Mental State
      Examination (MMSE) collected at baseline and rates of future crash involvement in
      a prospective population-based sample of older drivers. Motor vehicle collision
      involvement was obtained from the Alabama Department of Public Safety. Poisson
      regression was used to calculate crude and adjusted rate ratios (RR). Older
      drivers having difficulties in place orientation were more than 6 times (95% CI
      1.90-19.86) more likely to be involved in a future crash (adjusted RR = 6.14, 95%
      confidence interval (CI) 1.90-19.86) and at-fault crash (adjusted RR=6.39, 95% CI
      1.51-27.10). Impairment in the other cognitive areas was not associated with
      higher rates of crash or at-fault crash involvement. The findings were validated
      in an independent sample of high-risk older drivers and a similar pattern of
      results was observed. Spatial orientation impairment can help identify older
      drivers who are more likely to crash in the future.

PMID- 29594175
TI  - Multiple inflammasomes may regulate the interleukin-1-driven inflammation in
      protracted bacterial bronchitis.
AB  - Protracted bacterial bronchitis (PBB) in young children is characterised by
      prolonged wet cough, prominent airway interleukin (IL)-1beta expression and
      infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms
      responsible for IL-1-driven inflammation in PBB are poorly understood. We
      hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2
      inflammasome/IL-1beta axis. Lung macrophages obtained from bronchoalveolar lavage
      (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte
      derived macrophages from patients with PBB and age-matched healthy controls were
      cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14+
      monocytes contributed to 95% of total IL-1beta-producing cells upon NTHi
      stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1beta
      expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL
      1beta secretion in PBMCs from both healthy controls and patients with recurrent
      PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by
      MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome
      complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised
      with cleaved caspase-1 and cleaved IL-1beta. NTHi stimulation induced formation
      of specks of cleaved IL-1beta, NLRP3 and AIM2 in PBMCs, blood monocytes and
      monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2
      inflammasomes probably drive the IL-1beta-dominated inflammation in PBB.

PMID- 29594176
TI  - Scapular Dyskinesis in Young, Asymptomatic Elite Swimmers.
AB  - Background: Overhead athletes are at a greater risk of developing scapular
      dyskinesis (SD). Although swimming is considered an overhead sport, information
      regarding SD in these athletes is scarce. Purpose: To determine the prevalence of
      SD in young, asymptomatic elite swimmers. Study Design: Cross-sectional study;
      Level of evidence, 3. Methods: A total of 661 asymptomatic elite swimmers were
      enrolled in this study (344 male, 317 female; mean age, 15.83 +/- 2.20 years).
      Anthropometric characteristics, training routine, and stroke specialty were
      recorded. SD was assessed using a dynamic test consisting of an examination of
      the shoulder blades throughout synchronous forward flexion motion in the sagittal
      plane and was deemed to be either present or absent. Each movement was repeated 5
      times. These evaluations were performed with athletes at rest, before any
      training or competition. Statistical analysis was performed. Results: SD was
      detected in 56 (8.5%) participants. Type I SD was the most common (46.5%); male
      participants were 2 times as likely to have SD as female participants (39 male,
      17 female; P < .01). No correlation was found between the dominant limb and side
      affected (P = .258); rather, a correlation was found between the breathing side
      and side affected, in that swimmers with a preferred breathing side were more
      prone to develop SD in the opposite shoulder (P < .05). Swimmers involved in long
      distance races were found to have a greater risk of developing SD (P = .01).
      Conclusion: SD may be an asymptomatic condition in elite young swimmers and is
      present in 8.5% of these athletes. Early diagnosis may be useful for asymptomatic
      athletes with SD and to avoid its possible evolution to a symptomatic condition.

PMID- 29594178
TI  - Arthroscopic Management of Pigmented Villonodular Synovitis of the Hip in
      Children and Adolescents.
AB  - Background: Pigmented villonodular synovitis (PVNS) is a benign proliferative
      synovial disorder most commonly described to affect the knee in adults.
      Literature describing PVNS in the pediatric population is limited to 2 small case
      series and a handful of single-patient case reports. Within these studies, only 2
      patients with PVNS of the hip are described. Purpose: To describe the
      presentation, management, and outcomes of a single-center series of pediatric
      patients with PVNS of the hip treated with arthroscopic synovectomy. Study
      Design: Case series; Level of evidence, 4. Methods: A retrospective review of
      consecutive pediatric patients treated for PVNS at a single institution was
      performed. Inclusion criteria consisted of patients younger than 19 years with
      surgically treated PVNS of the hip. Results: Five pediatric patients with a mean
      age of 11.0 years were treated for PVNS of the hip from 2011 to 2016. The mean
      duration of symptoms from onset to surgical treatment was 247 days (range, 3-933
      days). Upon review of magnetic resonance imaging (MRI) results, radiologists
      included PVNS in their differential in 3 patients. Seven surgeries were performed
      in 5 patients. All therapeutic procedures were arthroscopic synovectomies.
      Nodular PVNS was present in 4 patients, and diffuse disease was present in 1
      patient. At a mean 32-month follow-up (range, 12-63 months), all patients were
      considered to be free of recurrence based on clinical examination and/or follow
      up MRI. Four patients were asymptomatic and returned to all of their previous
      sports activities. Conclusion: Young age at the time of diagnosis is a point to
      be highlighted in this cohort, and symptoms may be present for many months prior
      to diagnosis due to the failure to consider PVNS in children. Therefore, for
      patients with "atypical" presentations or lack of improvement with treatment for
      rheumatologic, bleeding, or infectious disorders, PVNS should be strongly
      considered. MRI with gradient echo sequences is the diagnostic imaging study of
      choice. One patient with diffuse involvement and preoperative degenerative
      changes showed progressive changes postoperatively. This type of PVNS may have a
      worse prognosis, but more diffuse cases are needed before the prognosis can be
      determined. Arthroscopic synovectomy following a timely diagnosis of PVNS
      produces good outcomes in nodular cases, with no evidence of symptomatic or
      radiographic disease persistence among these patients.

PMID- 29594179
TI  - Intervention Packages to Reduce the Impact of HIV and HCV Infections Among People
      Who Inject Drugs in Eastern Europe and Central Asia: A Modeling and Cost
      effectiveness Study.
AB  - Background: We evaluated the effectiveness and cost-effectiveness of
      interventions targeting hepatitis C virus (HCV) and HIV infections among people
      who inject drugs (PWID) in Eastern Europe/Central Asia. We specifically
      considered the needle-syringe program (NSP), opioid substitution therapy (OST),
      HCV and HIV diagnosis, antiretroviral therapy (ART), and/or new HCV treatment
      (direct acting antiviral [DAA]) in Belarus, Georgia, Kazakhstan, Republic of
      Moldova, and Tajikistan. Methods: We developed a deterministic dynamic
      compartmental model and evaluated the number of infections averted, costs, and
      incremental cost-effectiveness ratios (ICERs) of interventions. OST decreased
      frequencies of injecting by 85% and NSP needle sharing rates by 57%; ART was
      introduced at CD4 <350 and DAA at fibrosis stage >=F2 at a $2370 to $23 280 cost.
      Results: Increasing NSP+OST had a high impact on transmissions (infections
      averted in PWID: 42% in Tajikistan to 55% in Republic of Moldova for HCV; 30% in
      Belarus to 61% in Kazakhstan for HIV over 20 years). Increasing NSP+OST+ART was
      very cost-effective in Georgia (ICER = $910/year of life saved [YLS]), and was
      cost-saving in Kazakhstan and Republic of Moldova. NSP+OST+ART and HIV diagnosis
      was very cost-effective in Tajikistan (ICER = $210/YLS). Increasing the coverage
      of all interventions was always the most effective strategy and was cost
      effective in Belarus and Kazakhstan (ICER = $12 960 and $21 850/YLS); it became
      cost-effective/cost-saving in all countries when we decreased DAA costs.
      Conclusion: Increasing NSP+OST coverage, in addition to ART and HIV diagnosis,
      had a high impact on both epidemics and was very cost-effective and even cost
      saving. When HCV diagnosis was improved, increased DAA averted a high number of
      new infections if associated with NSP+OST.

PMID- 29594177
TI  - 2018 International Olympic Committee Consensus Statement on Prevention,
      Diagnosis, and Management of Pediatric Anterior Cruciate Ligament Injuries.
AB  - In October 2017, the International Olympic Committee hosted an international
      expert group of physical therapists and orthopaedic surgeons who specialize in
      treating and researching pediatric anterior cruciate ligament (ACL) injuries. The
      purpose of this meeting was to provide a comprehensive, evidence-informed summary
      to support the clinician and help children with ACL injury and their
      parents/guardians make the best possible decisions. Representatives from the
      following societies attended: American Orthopaedic Society for Sports Medicine;
      European Paediatric Orthopaedic Society; European Society for Sports
      Traumatology, Knee Surgery, and Arthroscopy; International Society of
      Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine; Pediatric Orthopaedic
      Society of North America; and Sociedad Latinoamericana de Artroscopia, Rodilla, y
      Deporte. Physical therapists and orthopaedic surgeons with clinical and research
      experience in the field and an ethics expert with substantial experience in the
      area of sports injuries also participated. This consensus statement addresses 6
      fundamental clinical questions regarding the prevention, diagnosis, and
      management of pediatric ACL injuries. Injury management is challenging in the
      current landscape of clinical uncertainty and limited scientific knowledge.
      Injury management decisions also occur against the backdrop of the complexity of
      shared decision making with children and the potential long-term ramifications of
      the injury.

PMID- 29594180
TI  - Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia.
AB  - Background: Penicillin allergy frequently impacts antibiotic choice. As beta
      lactams are superior to vancomycin in treating methicillin-susceptible
      Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported
      penicillin allergy on clinical outcomes in patients with MSSA bacteremia.
      Methods: In this retrospective cohort study of adults with MSSA bacteremia
      admitted to a large tertiary care hospital, outcomes were examined according to
      reported penicillin allergy. Primary outcomes included 30-day and 90-day
      mortality rates. Multivariable regression models were developed to quantify the
      effect of reported penicillin allergy on mortality while adjusting for potential
      confounders. Results: From 2010 to 2015, 318 patients with MSSA bacteremia were
      identified. Reported penicillin allergy had no significant effect on adjusted 30
      day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29-1.84; P
      = .51). Patients with reported penicillin allergy were more likely to receive
      vancomycin (38% vs 11%, P < .01), but a large number received cefazolin
      regardless of reported allergy (29 of 66, 44%). Mortality rates were highest
      among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those
      receiving beta-lactams regardless of reported allergy, P < .01). In multivariable
      analysis, beta-lactam receipt was most strongly associated with survival (OR,
      0.26; 95% CI, 0.12-0.54). Conclusions: Reported penicillin allergy had no
      significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients
      receiving vancomycin for treatment of MSSA bacteremia had the highest mortality
      rates overall. Receipt of a beta-lactam was the strongest predictor of survival.
      These results underscore the importance of correct classification of patients
      with penicillin allergy and appropriate treatment with a beta-lactam when
      tolerated.

PMID- 29594181
TI  - Predicting malignant nodules by fusing deep features with classical radiomics
      features.
AB  - Lung cancer has a high incidence and mortality rate. Early detection and
      diagnosis of lung cancers is best achieved with low-dose computed tomography
      (CT). Classical radiomics features extracted from lung CT images have been shown
      as able to predict cancer incidence and prognosis. With the advancement of deep
      learning and convolutional neural networks (CNNs), deep features can be
      identified to analyze lung CTs for prognosis prediction and diagnosis. Due to a
      limited number of available images in the medical field, the transfer learning
      concept can be helpful. Using subsets of participants from the National Lung
      Screening Trial (NLST), we utilized a transfer learning approach to differentiate
      lung cancer nodules versus positive controls. We experimented with three
      different pretrained CNNs for extracting deep features and used five different
      classifiers. Experiments were also conducted with deep features from different
      color channels of a pretrained CNN. Selected deep features were combined with
      radiomics features. A CNN was designed and trained. Combinations of features from
      pretrained, CNNs trained on NLST data, and classical radiomics were used to build
      classifiers. The best accuracy (76.79%) was obtained using feature combinations.
      An area under the receiver operating characteristic curve of 0.87 was obtained
      using a CNN trained on an augmented NLST data cohort.

PMID- 29594182
TI  - Model-based quantitative optical biopsy in multilayer in vitro soft tissue models
      for whole field assessment of nonmelanoma skin cancer.
AB  - Optical techniques such as fluorescence and diffuse reflectance spectroscopy are
      proven to have the potential to provide tissue discrimination during the
      development of malignancies and hence treated as potential tools for noninvasive
      optical biopsy in clinical diagnostics. Quantitative optical biopsy is
      challenging and hence the majority of the existing strategies are based on a
      qualitative assessment of the concerned tissue. Light-tissue interaction models
      as well as precise optical phantoms can greatly help in the former and here we
      present a pilot study to assess the optical properties of a multilayer tissue
      specific optical phantom with the help of a database generated using multilayer
      Monte Carlo (MCML) models. A set of optical models mimicking the properties of
      actual and diseased conditions of tissues associated with nonmelanoma skin cancer
      (NMSC) were devised and MCML simulations of fluorescence and diffuse reflectance
      were performed on these models to generate the spectral signature of identified
      biomarkers of NMSC such as hemoglobin, flavin adenine dinucleotide, and collagen.
      A model library was generated and with the extracted features from modeled
      spectra, classification of normal and NMSC conditions were tested using the
      [Formula: see text]-nearest neighbor (KNN) classifier. Using an in-house
      assembled scan-based automated bimodal spectral imaging system with reflectance
      and fluorescence modalities of operation, a layered, thin, tissue equivalent
      phantom, fabricated with controlled optical properties mimicking normal and NMSC
      conditions were tested. The spectral signatures corresponding to the NMSC
      biomarkers were acquired from this phantom and extracted features from the
      spectra were tested using the KNN classifier and classification accuracy of 100%
      was achieved. For further quantitative analysis, the experimental and simulated
      spectra were compared with respect to the light intensity at the emission peak or
      absorption dips, spectral line width, and average intensity over a range of
      wavelength of interest and observed to be analogous within specified and
      systematic error limits. This methodology is expected to give a better
      quantitative approach for estimation of tissue properties by correlating the
      experimental and simulated data.

PMID- 29594183
TI  - Patient-specific cardiac phantom for clinical training and preprocedure surgical
      planning.
AB  - Minimally invasive mitral valve repair procedures including MitraClip(r) are
      becoming increasingly common. For cases of complex or diseased anatomy,
      clinicians may benefit from using a patient-specific cardiac phantom for
      training, surgical planning, and the validation of devices or techniques. An
      imaging compatible cardiac phantom was developed to simulate a MitraClip(r)
      procedure. The phantom contained a patient-specific cardiac model manufactured
      using tissue mimicking materials. To evaluate accuracy, the patient-specific
      model was imaged using computed tomography (CT), segmented, and the resulting
      point cloud dataset was compared using absolute distance to the original patient
      data. The result, when comparing the molded model point cloud to the original
      dataset, resulted in a maximum Euclidean distance error of 7.7 mm, an average
      error of 0.98 mm, and a standard deviation of 0.91 mm. The phantom was validated
      using a MitraClip(r) device to ensure anatomical features and tools are
      identifiable under image guidance. Patient-specific cardiac phantoms may allow
      for surgical complications to be accounted for preoperative planning. The
      information gained by clinicians involved in planning and performing the
      procedure should lead to shorter procedural times and better outcomes for
      patients.

PMID- 29594184
TI  - Photoacoustic-based catheter tracking: simulation, phantom, and in vivo studies.
AB  - Catheters are commonly used in many procedures and tracking and localizing them
      is critical to patient safety and surgical success. The standard of care for
      catheter tracking is with the use of fluoroscopy. Alternatives using conventional
      tracking technologies such as electromagnetic trackers have been previously
      explored. This work explores the use of an emerging imaging modality,
      photoacoustics, as a means for tracking. A piezoelectric (PZT) sensor is placed
      at the tip of the catheter, allowing it to receive the acoustic signals generated
      from photoacoustic markers due to the photoacoustic effect. The locations of
      these photoacoustic markers are determined by a stereo-camera and the received
      acoustic signals are converted into distances between the PZT element and the
      photoacoustic markers. The location of the PZT sensor can be uniquely determined
      following a multilateration process. This work validates this photoacoustic
      tracking method in phantom, simulation, and in vivo scenarios using metrics
      including reconstruction precision, relative accuracy, estimated accuracy, and
      leave-out accuracy. Submillimeter tracking results were achieved in phantom
      experiments. Simulation studies evaluated various physical parameters relating to
      the photoacoustic source and the PZT sensor. In vivo results showed feasibility
      for the eventual deployment of this technology.

PMID- 29594185
TI  - Ab Initio Optimized Effective Potentials for Real Molecules in Optical Cavities:
      Photon Contributions to the Molecular Ground State.
AB  - We introduce a simple scheme to efficiently compute photon exchange-correlation
      contributions due to the coupling to transversal photons as formulated in the
      newly developed quantum-electrodynamical density-functional theory (QEDFT).1-5
      Our construction employs the optimized-effective potential (OEP) approach by
      means of the Sternheimer equation to avoid the explicit calculation of unoccupied
      states. We demonstrate the efficiency of the scheme by applying it to an exactly
      solvable GaAs quantum ring model system, a single azulene molecule, and chains of
      sodium dimers, all located in optical cavities and described in full real space.
      While the first example is a two-dimensional system and allows to benchmark the
      employed approximations, the latter two examples demonstrate that the correlated
      electron-photon interaction appreciably distorts the ground-state electronic
      structure of a real molecule. By using this scheme, we not only construct typical
      electronic observables, such as the electronic ground-state density, but also
      illustrate how photon observables, such as the photon number, and mixed electron
      photon observables, for example, electron-photon correlation functions, become
      accessible in a density-functional theory (DFT) framework. This work constitutes
      the first three-dimensional ab initio calculation within the new QEDFT formalism
      and thus opens up a new computational route for the ab initio study of correlated
      electron-photon systems in quantum cavities.

PMID- 29594186
TI  - Antimatched Electromagnetic Metasurfaces for Broadband Arbitrary Phase
      Manipulation in Reflection.
AB  - Metasurfaces impart phase discontinuities on impinging electromagnetic waves that
      are typically limited to 0-2pi. Here, we demonstrate that multiresonant
      metasurfaces can break free from this limitation and supply arbitrarily large,
      tunable time delays over ultrawide bandwidths. As such, ultrathin metasurfaces
      can act as the equivalent of thick bulk structures by emulating the multiple
      geometric resonances of three-dimensional systems that originate from phase
      accumulation with effective material resonances implemented on the surface itself
      via suitable subwavelength meta-atoms. We describe a constructive procedure for
      defining the required sheet admittivities of such metasurfaces. Importantly, the
      proposed approach provides an exactly linear phase response so that broadband
      pulses can experience the desired group delay without any distortion of the pulse
      shape. We focus on operation in reflection by exploiting an antimatching
      condition, satisfied by interleaved electric and magnetic Lorentzian resonances
      in the surface admittivities, which completely zeroes out transmission through
      the metasurface. As a result, the proposed metasurfaces can perfectly reflect a
      broadband pulse imparting a prescribed group delay. The group delay can be tuned
      by modifying the implemented resonances, thus opening up diverse possibilities in
      the temporal applications of metasurfaces.

PMID- 29594187
TI  - Biochemical Isolation of Myonuclei from Mouse Skeletal Muscle Tissue.
AB  - Skeletal muscle provides the contractile force necessary for movement,
      swallowing, and breathing and, consequently, is necessary for survival. Skeletal
      muscle cells are unique in that they are extremely large cells containing
      thousands of nuclei. These nuclei must all work in concert to maintain skeletal
      muscle function and thereby maintain life. The nucleus is a major site of
      signaling integration and gene expression regulation. However, examining nuclear
      processes in skeletal muscle can be difficult because myonuclei are challenging
      to isolate. We optimized a protocol to purify myonuclei from whole muscle tissue
      using ultracentrifugation over a discontinuous sucrose gradient to separate the
      nuclear fraction. We used these purified nuclei for downstream applications
      including flow cytometry and mass spectrometry. We used this method to compare
      the myonuclear proteome of young and old mouse hindlimb muscles (Cutler et al.,
      2017). This protocol may be applied to isolating myonuclei for a variety of
      downstream analyses such as flow cytometry, microscopy, Western blot, and
      proteomics.

PMID- 29594188
TI  - Dual-sided Voltage-sensitive Dye Imaging of Leech Ganglia.
AB  - In this protocol, we introduce an effective method for voltage-sensitive dye
      (VSD) loading and imaging of leech ganglia as used in Tomina and Wagenaar (2017).
      Dissection and dye loading procedures are the most critical steps toward
      successful whole-ganglion VSD imaging. The former entails the removal of the
      sheath that covers neurons in the segmental ganglion of the leech, which is
      required for successful dye loading. The latter entails gently flowing a new
      generation VSD, VF2.1(OMe).H, onto both sides of the ganglion simultaneously
      using a pair of peristaltic pumps. We expect the described techniques to
      translate broadly to wide-field VSD imaging in other thin and relatively
      transparent nervous systems.

PMID- 29594189
TI  - Incentive Design and Quality Improvements: Evidence from State Medicaid Nursing
      Home Pay-for-Performance Programs.
AB  - Pay-for-performance (P4P) programs have become a popular policy tool aimed at
      improving health care quality. We analyze how incentive design affects quality
      improvements in the nursing home setting, where several state Medicaid agencies
      have implemented P4P programs that vary in incentive structure. Using the Minimum
      Data Set and the Online Survey, Certification, and Reporting data from 2001 to
      2009, we examine how the weights put on various performance measures that are
      tied to P4P bonuses, such as clinical outcomes, inspection deficiencies, and
      staffing levels, affect improvements in those measures. We find larger weights on
      clinical outcomes often lead to larger improvements, but small weights can lead
      to no improvement or worsening of some clinical outcomes. We find a qualifier for
      P4P eligibility based on having few or no severe inspection deficiencies is more
      effective at decreasing inspection deficiencies than using weights, suggesting
      simple rules for participation may incent larger improvement.

PMID- 29594190
TI  - Complex Pulmonary Aspergilloma: Surgical Challenges in a Third World Setting.
AB  - Background: Surgery for pulmonary aspergilloma (PA), especially complex forms, is
      greatly challenging in a resource-poor setting such as Cameroon. We report our
      experience of surgical management of PA in this environment. Method: We
      prospectively assessed patients who underwent surgery for PA from January 2012 to
      May 2015, at the University Hospital Center of Yaounde. Records were reviewed for
      demographics, history and physical examinations, radiological findings, surgical
      procedures, and outcomes. The study has received approval from the institutional
      ethics committees. Results: In total, 20 patients (17 males and 3 females (sex
      ratio, 5.66); mean age, 30 years; range, 23-65 years) with a past history of
      tuberculosis were assessed. The median follow-up was 21.5 months. The primary
      symptom was hemoptysis, followed by cough and chest pain. All patients underwent
      surgical treatment and lung resection. Postoperative complications (bleeding, air
      leak, empyema, and severe anemia) occurred in 4 patients and 1 patient died.
      Although 3 patients were lost to follow-up, the survival rate was 80% with
      improvement of the preoperative symptoms. Conclusion: Although surgery for
      complex aspergilloma is very challenging in environments such as ours, we believe
      that it is the best treatment modality for symptomatic diseases in our setting.

PMID- 29594191
TI  - Nutrition Education in Internal Medicine Residency Programs and Predictors of
      Residents' Dietary Counseling Practices.
AB  - Background: Although physicians are expected to provide dietary counseling for
      patients with cardiovascular (CV) risk factors such as hypertension,
      hyperlipidemia, diabetes, and obesity, nutrition education in graduate medical
      education remains limited. Few studies have recently examined nutrition education
      and dietary counseling practices in Internal Medicine (IM) residency training.
      Objectives: To conduct a contemporary assessment of outpatient nutrition
      education in IM residency programs in the United States, identify predictors of
      residents' dietary counseling practices for CV risk factors, and identify
      barriers for educators in providing nutrition education and barriers for
      residents in counseling patients. Design: Cross-sectional anonymous surveys were
      completed by IM program directors (PDs) and residents throughout the United
      States. Linear regression was used to examine the association between the amount
      of nutrition education received and the number of instruction methods used by the
      residents and frequency of residents' dietary counseling for patients with CV
      risk factors. Key Results: A total of 40 educators (PDs and ambulatory/primary
      care PDs) and 133 residents across the United States responded to the survey.
      About 61% of residents reported having very little or no training in nutrition.
      Nutrition education in residency, both the amount of education (beta = 0.20, P =
      .05) and the number of instruction methods used (beta = 0.26, P = .02), predicted
      frequency of residents' dietary counseling practices independent of nutrition
      education in medical school, which was also significantly associated with
      counseling (beta = 0.20, P = .03). Residents' total fruit and vegetable intake
      likewise predicted frequency of counseling (beta = 0.24, P < .001). Low perceived
      faculty expertise was a major barrier for educators and was associated with lower
      level of provided nutrition education (r = -.33, P = .04). Low resident and low
      perceived clinic preceptors' interests in nutrition were also associated with
      lower frequency of residents' dietary counseling (r = -.19, P = .04; r = -.18, P
      = .05). Conclusions: The provision of nutrition education in IM residency
      programs and IM residents' dietary counseling for patients need to be
      systematically assessed nationally. This study's preliminary findings suggest
      that multimodal nutrition education in IM residency and better resident dietary
      habits are associated with higher frequency of dietary counseling for patients.
      Lack of faculty expertise and low faculty and resident interests in patient
      counseling need to be addressed perhaps by mandating nutrition education in
      graduate and continuing medical education.

PMID- 29594193
TI  - Expression of intrahepatic CD3, CD4, and CD8 T cells in biliary atresia.
AB  - Aim of the study: Assessment of the expression of cluster of differentiation
      (CD)3, CD4, and CD8 T cells in biliary atresia (BA) cases in comparison to
      neonatal cholestasis other than BA. Material and methods: This study included 79
      patients: 34 patients with BA (BA group) and 35 patients with neonatal
      cholestasis due to causes other than BA (cholestasis group), and 10 normal liver
      donor as a control group. Immunohistochemical staining or CD3, CD4, and CD8 T
      cells in liver tissues for the 3 groups were evaluated. Results: Presence of clay
      stool, high gamma-glutamyl transferase levels, thrombocytosis, and non
      contractibility of the gallbladder was the main clinical, laboratory, and
      radiological findings, distinguishing BA from other disorders causing neonatal
      cholestasis. Portal ductular proliferation, bile plugs in portal ductules, and
      advanced grades of fibrosis were more predominant in liver biopsy specimens of BA
      patients. The CD3+, CD4+, and CD8+ expression in patients with BA were
      significantly higher than in both cholestasis and control groups, while it was
      comparable in the cholestasis and control groups, with cutoff values of 25, 12,
      and 2.5 cells/portal tract, respectively, differentiating between BA and
      cholestatic patients. Conclusions: Immune-mediated destruction of bile ducts is
      incriminated in the pathogenesis of BA. Lymphocytic infiltrate in portal tract is
      primarily composed of CD3, CD4, and CD8 T cells. Immunostaining of liver tissue
      for CD3, CD4, and CD8 T cells can help in ensuring diagnosis of BA.

PMID- 29594192
TI  - The influence of NAFLD on the risk of atherosclerosis and cardiovascular
      diseases.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease in developed countries and is associated with obesity, dyslipidaemia,
      diabetes, and metabolic syndrome. Atherosclerosis and cardiovascular diseases are
      also highly prevalent in this group of patients, due to the presence of shared
      risk factors. The incidences of coronary artery calcification, hypertension,
      aortic valve sclerosis, diastolic dysfunction, atherosclerotic plaques, and
      increased carotid intima-media thickness were more common in patients with NAFLD
      than in those without. The present paper reviews the medical literature
      concerning the association between NAFLD and cardiovascular events.

PMID- 29594194
TI  - The epidemiology of hepatocellular cancer in Poland.
AB  - Introduction: This article summarize the available data on hepatocellular
      carcinoma (HCC) epidemiology in Poland. Data regarding the HCC incidence rate are
      divergent. Statistical data presented by NFZ appear more credible in that matter
      than data published by the Polish Oncology Center (POC). Material and methods:
      The analysis included data from the Polish Bibliography Database (GBL), the
      Polish National Health Fund Institution (NFZ), the scientific paper "Malignant
      neoplasms in Poland" issued by POC and the central liver transplant registry
      maintained by the Polish transplant coordinating center "Poltransplant" (2010
      2015). Results: Data regarding the HCC incidence rate are divergent. Statistical
      data presented by NFZ appear more credible in that matter than data published by
      POC. Conclusions: The occurrence of HCC in Poland is at the average European
      level and is similarly rising. The incidence rate is underestimated. It is due to
      faulty epidemiology data collection techniques. The highest risk group comprises
      men over the age of 50 with concomitant liver cirrhosis. The most common HCC
      etiology is HCV infection.

PMID- 29594195
TI  - Effects of infection on post-transplant outcomes: living versus deceased donor
      liver transplants.
AB  - Introduction: Post-transplant infections have been studied widely but data on
      comparisons of deceased donor liver transplants (DDLT) and living donor liver
      transplants (LDLT), type and timings of infections, and their relations to
      outcomes are not explored. Material and methods: We analysed data from 612
      participants of the Adult-to-Adult Living Donor Liver Transplantation Study
      (A2ALL), a retrospective data set of LDLT and DDLT. We compared the type and
      timing of the first post-transplant infection in relation to transplant outcomes
      between the two groups. Results: Out of 611 patients, 24.5% experienced the first
      post-transplant infection, the majority of which were bacterial (35.3%), followed
      by fungal (11%) and viral infections (4.2%). There was no significant difference
      in the rate, type or timing of infection between LDLT and DDLT. Patients with
      late (> 1 year) first infection were 1.8 times more likely to die (95% CI: 1.12
      2.98, p = 0.015) and 9 times more likely to have graft failures (95% CI: 3.26
      24.8, p < 0.001). DDLT recipients who experienced bacterial infection had a
      significantly lower survival rate compared to LDLT recipients (p < 0.001).
      Conclusions: Late infection is associated with lower survival in both DDLT and
      LDLT. Bacterial infection might be more detrimental for DDLT than LDLT. Late
      infection should be managed aggressively to improve outcomes.

PMID- 29594196
TI  - Evaluation of serum interleukin-10 levels in hepatocellular carcinoma patients: a
      systematic review and meta-analysis.
AB  - Aim of the study: This meta-analysis aimed to evaluate serum IL-10 levels in HCC
      patients. Material and methods: The three databases PubMed, Scopus and Web of
      Science were checked on July 2017 for assessment of IL-10 levels in
      hepatocellular carcinoma (HCC) patients compared with healthy controls in
      publications with an English abstract. A random-effect meta-analysis was
      performed using mean difference (MD) and 95% confidence intervals (CIs). Also,
      publication bias was evaluated through funnel plot analysis with the Begg's and
      Egger's tests. Results: Out of 171 studies searched in the databases, nine
      studies were included in the meta-analysis. The pooled analysis with continuous
      data concluded that IL-10 level in the patients was significantly higher than the
      controls (MD = 6.96; 95% CI = 4.91-9.01; p < 0.00001), in the HCC patients was
      significantly higher than the cirrhotic patients (MD = 2.92; 95% CI = 0.72-5.12;
      p = 0.009), and was similar in the HCC patients compared with the patients with
      hepatitis (MD = 3.91; 95% CI = -4.25-12.07; p = 0.35). Conclusion: The increased
      IL-10 levels in the HCC patients compared with the cirrhotic patients and the
      healthy controls may show a significant role of this cytokine in the elevated
      risk of HCC, but the lack of significant difference in the levels between HCC and
      hepatitis makes it an unreliable tumor marker in the latter.

PMID- 29594197
TI  - Cannulation in patients with large periampullary diverticulum using SpyBite
      miniforceps.
AB  - Introduction: Cannulation is difficult in patients with periampullary
      diverticulum (PAD). The described success rate varies from 61% to 95.4%. Material
      and methods: Four cases with PAD in which, despite repeated attempts, we were
      unable to locate the papilla and cannulate. To overcome this difficulty, we used
      SpyBite forceps (Boston Scientific) to pull out the papillary orifice and then
      perform the cannulation using a sphincterotome introduced through the same
      working channel. Results: This method reduced the time required for cannulation.
      In all four of our cases, we had 100% success in cannulation. Conclusions: Use of
      SpyBite miniforceps in difficult cannulations in patients with PAD is useful and
      has an excellent success rate.

PMID- 29594198
TI  - Hepatic infarction and acute pancreatitis: a case report and review of the
      literature.
AB  - Hepatic infarction is rare due to the unique dual hepatic blood supply from the
      hepatic artery and the portal vein. Herein, we report a case of hepatic
      infarction that occurred as a complication of acute pancreatitis. The patient was
      a 58-year-old male with past medical history of chronic alcoholism, who presented
      with epigastric abdominal pain, nausea, and vomiting. Hepatic infarction was
      diagnosed with computed tomography of the abdomen and pelvis without contrast,
      which revealed suspicion of splenic vein thrombosis and peripancreatic fat
      stranding along with a wedge-shaped, peripheral hypo density in the right hepatic
      lobe with typical morphology for hepatic infarction.

PMID- 29594199
TI  - Hemospray for recurrent esophageal band ulcer bleeding.
AB  - Rebleeding after initially successful endoscopic variceal ligation (EVL) occurs
      in 20-60% of patients, most commonly from band ulcers, and is associated with 20
      50% mortality. Although band ulcer bleeding has been treated in a number of
      different ways, no single therapeutic intervention has shown a clear benefit.
      Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a relatively new
      non-contact hemostatic modality used in the management of bleeding peptic ulcers.
      It is a nano-powder that can be sprayed over a larger mucosal area. Here we
      describe a patient with end stage liver disease who presented with recurrent
      bleeding from a deep esophageal ulcer following band ligation and sclerotherapy,
      effectively managed with multiple sessions of Hemospray.

PMID- 29594200
TI  - Structural alterations by five disease-causing mutations in the low-pH
      conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by
      molecular dynamics - Implications in functional loss and modulation of reactive
      oxygen species generation by pathogenic hLADH forms.
AB  - Human dihydrolipoamide dehydrogenase (hLADH) is a flavoenzyme component (E3) of
      the human alpha-ketoglutarate dehydrogenase complex (alpha-KGDHc) and few other
      dehydrogenase complexes. Pathogenic mutations of hLADH cause severe metabolic
      diseases (atypical forms of E3 deficiency) that often escalate to cardiological
      or neurological presentations and even premature death; the pathologies are
      generally accompanied by lactic acidosis. hLADH presents a distinct conformation
      under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of
      generating reactive oxygen species (ROS). It has been shown by our laboratory
      that selected pathogenic mutations, besides lowering the physiological activity
      of hLADH, significantly stimulate ROS generation by hLADH, especially at lower
      pH, which might play a role in the pathogenesis of E3-deficiency in respective
      cases. Previously, we generated by molecular dynamics (MD) simulation the low-pH
      hLADH structure and analyzed the structural changes induced in this structure by
      eight of the pathogenic mutations of hLADH. In the absence of high resolution
      mutant structures these pieces of information are crucial for the mechanistic
      investigation of the molecular pathogeneses of the hLADH protein. In the present
      work we analyzed by molecular dynamics simulation the structural changes induced
      in the low-pH conformation of hLADH by five pathogenic mutations of hLADH; the
      structures of these disease-causing mutants of hLADH have never been examined
      before.

PMID- 29594201
TI  - Association of lung fluorodeoxyglucose uptake with radiation pneumonitis after
      concurrent chemoradiation for non-small cell lung cancer.
AB  - Background: Increased uptake of fluorodeoxyglucose (FDG) by lung tissue could
      reflect inflammatory changes related to radiation pneumonitis (RP). In this
      secondary analysis of a clinical trial, we examined potential associations
      between posttreatment lung FDG uptake and RP severity in patients with non-small
      cell lung cancer (NSCLC) for up to 12 months after concurrent chemoradiation
      (CRT). Methods: Subjects were 152 patients with NSCLC who had received concurrent
      CRT as part of the prospective trial NCT00915005. The following lung FDG
      variables were evaluated after CRT: maximum, mean, and peak standardized uptake
      values (SUVmax, SUVmean, SUVpeak) and global lung glycolysis (GLG; lung SUVmean *
      lung volume). RP severity was scored with the Common Terminology Criteria for
      Adverse Events v3.0. Results: Significant associations were noted between PET
      findings and RP severity at 1-6 months (all P < 0.05), but not at 7-12 months
      after therapy (all P > 0.05). Lung FDG uptake at 1-3 months after treatment
      predicted later development of grade >=2 RP (all P < 0.05), with cutoff values as
      follows: 4.54 for SUVmax, 3.69 for SUVpeak, 0.78 for SUVmean, and 2295 for GLG.
      Conclusions: Lung FDG uptake correlated significantly with RP severity during the
      first 6 months after CRT. The cutoff values seem clinically meaningful for
      identifying patients at risk of developing RP after such therapy.

PMID- 29594202
TI  - Time to surgery and pathologic complete response after neoadjuvant chemoradiation
      in rectal cancer: A population study on 2094 patients.
AB  - Background: To retrospectively evaluate the difference in terms of pathologic
      complete response (pCR) according to time elapsed between chemoradiation (CRT)
      and total mesorectal excision (TME) on a large unselected real-life dataset of
      locally advanced rectal cancer (LARC) patients. Methods: A multicentre
      retrospective cohort study of LARC patients from 21 Italian Radiotherapy
      Institutions was performed. Patients were stratified into 3 different time
      intervals from CRT. The 1st group included 300 patients who underwent TME within
      6 weeks, the 2nd 1598 patients (TME within 7-12 weeks) and the 3rd 196 patients
      (TME within 13 or more weeks after CRT), respectively. Results: Data on 2094 LARC
      patients treated between 1997 and 2016 were considered suitable for analysis.
      Overall, 578 patients had stage II while 1516 had stage III histological proven
      invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs
      (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The
      proportion of patients achieving pCR with respect to time interval was, as
      follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001),
      respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while
      3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative
      risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p <
      0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001)
      were significantly correlated to pCR. The positive impact of interval (p < 0.001)
      was confirmed at multivariate analysis as the only correlated factor. Conclusion:
      We confirmed on a population-level that lengthening the interval (>13 weeks) from
      CRT to surgery improves the pathological response (pCR and pathologic partial
      response; pPR) in comparison to historic data. Furthermore, radiotherapy dose
      >5040 cGy and two drugs chemotherapy correlated with pPR rate.

PMID- 29594203
TI  - Association between cumulative radiation dose, adverse skin reactions, and
      changes in surface hemoglobin among women undergoing breast conserving therapy.
AB  - Introduction: Radiation therapy is crucial to effective cancer treatment. Modern
      treatment strategies have reduced possible skin injury, but few clinical studies
      have addressed the dose relationship between radiation exposure and skin
      reaction. This prospective clinical study analyzes skin oxygenation/perfusion in
      patients undergoing fractionated breast conserving therapy via hyperspectral
      imaging (HSI). Methods: Forty-three women undergoing breast conserving therapy
      were enrolled in this study. Optically stimulated luminescent dosimeters (OSLDs)
      measured radiation exposure in four sites: treatment breast, lumpectomy scar,
      medial tattoo and the control breast. The oxygenation/perfusion states of these
      sites were prospectively imaged before and after each treatment fraction with
      HSI. Visual skin reactions were classified according to the RTOG system. Results:
      2753 observations were obtained and indicated a dose-response relationship
      between radiation exposure and oxygenated hemoglobin (OxyHb) after a 600 cGy
      cumulative dose threshold. There was a relatively weak association between
      DeoxyHb and radiation exposure. Results suggest strong correlations between
      changes in mean OxyHb and skin reaction as well as between radiation exposure and
      changes in skin reaction. Conclusion: HSI demonstrates promise in the assessment
      of skin dose as well as an objective measure of skin reaction. The ability to
      easily identify adverse skin reactions and to modify the treatment plan may
      circumvent the need for detrimental treatment breaks.

PMID- 29594204
TI  - Infrastructure and distributed learning methodology for privacy-preserving multi
      centric rapid learning health care: euroCAT.
AB  - Machine learning applications for personalized medicine are highly dependent on
      access to sufficient data. For personalized radiation oncology, datasets
      representing the variation in the entire cancer patient population need to be
      acquired and used to learn prediction models. Ethical and legal boundaries to
      ensure data privacy hamper collaboration between research institutes. We
      hypothesize that data sharing is possible without identifiable patient data
      leaving the radiation clinics and that building machine learning applications on
      distributed datasets is feasible. We developed and implemented an IT
      infrastructure in five radiation clinics across three countries (Belgium,
      Germany, and The Netherlands). We present here a proof-of-principle for future
      'big data' infrastructures and distributed learning studies. Lung cancer patient
      data was collected in all five locations and stored in local databases. Exemplary
      support vector machine (SVM) models were learned using the Alternating Direction
      Method of Multipliers (ADMM) from the distributed databases to predict post
      radiotherapy dyspnea grade [Formula: see text]. The discriminative performance
      was assessed by the area under the curve (AUC) in a five-fold cross-validation
      (learning on four sites and validating on the fifth). The performance of the
      distributed learning algorithm was compared to centralized learning where
      datasets of all institutes are jointly analyzed. The euroCAT infrastructure has
      been successfully implemented in five radiation clinics across three countries.
      SVM models can be learned on data distributed over all five clinics. Furthermore,
      the infrastructure provides a general framework to execute learning algorithms on
      distributed data. The ongoing expansion of the euroCAT network will facilitate
      machine learning in radiation oncology. The resulting access to larger datasets
      with sufficient variation will pave the way for generalizable prediction models
      and personalized medicine.

PMID- 29594205
TI  - Effect of heterogeneous radio sensitivity on the survival, alpha beta ratio and
      biologic effective dose calculation of irradiated mammalian cell populations.
AB  - It is demonstrated that the surviving fraction of a population of cells with
      heterogeneous radio sensitivity, like that composing most malignant tumors,
      conforms to a different linear quadratic survival relation for dose less than
      about 3-5 Gy and dose greater than about 7-9 Gy. In the intermediate range of
      dose the survival relation for the population, as a whole, is not linear
      quadratic. Consequently, the value of the alpha beta ratio and the associated
      biologically effective dose calculation are different for the low and high dose
      range for most malignant tumors. Normal tissue cell populations responsible for
      organ function also have heterogeneous radio sensitivity, though to less degree
      than most malignant tumors. Consequently, the alpha beta ratio and associated
      biologically effective dose calculation related to the development of some acute
      early and chronic late developing radiation injuries are not the same in the low
      and high dose range. Variance of the distribution of alpha of a heterogeneous
      cell population lowers the effective value of the quadratic survival constant
      beta of the population, as a whole, and increases the alpha/beta ratio in the low
      dose range. Heterogeneous appearance of tumor cells (pleomorphism) and necrosis
      on biopsy or imaging studies reflect heterogeneity of the radio sensitivity of
      the cells. Greater heterogeneity implies a tendency to higher alpha/beta ratio.
      This may furnish a clinically accessible way to estimate a value of the
      alpha/beta ratio specific to an individual patient and tumor.

PMID- 29594206
TI  - Definitive radiation therapy for hepatocellular carcinoma with portal vein tumor
      thrombus.
AB  - Background: The purpose of this study is to review the results of radiation
      therapy (RT) for hepatocellular carcinoma (HCC) with portal venous tumor thrombus
      (PVTT) in a Western patient population. Methods: Thirty-four patients with HCC
      PVTT treated from 2007 to 2014 with RT were identified. Biologically effective
      dose (BED) was calculated for each patient, and greater than the median dose
      delivered (75 Gray (Gy)) was evaluated as a potential prognostic factor. Survival
      was compared and independent prognostic variables were evaluated by a Cox
      proportional hazards regression model. Results: Twenty-six patients (76.5%)
      exhibited a radiographic response to RT, and 10 patients (29.4%) ultimately
      developed local failure. Local control, liver control, distant control and OS at
      one year were 57.1%, 36.4%, 55.2% and 57.4%, respectively. Patients who received
      a BED >75 Gy had a significantly better local control at 1 year (93.3% vs 45.6%;
      Log Rank p = 0.0184). Patients who received a BED >75 Gy also had significantly
      better median survival (24.7mo vs 6.1mo) and 1-year overall survival (76.5% vs
      30.0%) when compared with BED <=75 Gy (Log-Rank p = 0.002). Conclusion: Our data
      suggest that RT should be considered for well-selected patients with HCC and PVTT
      for the purpose of improving local control and potentially prolonging the time to
      worsening venous obstruction and liver failure. When feasible, dose-escalation
      should be considered with a target BED of >75 Gy if normal organ dose constraints
      can be safely met.

PMID- 29594207
TI  - Patterns of loco regional failure in women with breast cancer treated by
      Postmastectomy Conformal Electron Beam Radiation Therapy (PMERT): Large scale
      single center experience.
AB  - Purpose: To evaluate loco regional control and describe the patterns of loco
      regional failure in women with breast cancer irradiated by a previously described
      post-mastectomy highly conformal electron beam radiotherapy technique. Materials
      and methods: We included all women irradiated by PMERT for non-metastatic breast
      cancer (BC) between 2007 and 2011 in our department. All cases of bilateral BC
      were excluded. All patients who experienced loco regional recurrence have been
      studied. Mapping patterns of regional recurrences was also performed and compared
      with the ESTRO and RTOG Guidelines of volume definition and delineation
      guidelines. Results: Among the 796 women included, 10.1% were triple-negative
      (TN) and 18.8% were HER2-positive and 24.6% of them had received neoadjuvant
      chemotherapy (CT). Internal mammary chain (IMC), supraclavicular (Level IV),
      infraclavicular (Levels III and II) and axillary LN (Level I) were treated in
      85.6%, 88.3%, 77.9% and 14.9% of cases, respectively. With a median follow-up of
      64 months (range: 6-102), 5-year locoregional (RFS and OS were 90% (95% CI: 88.1
      92.4) and 90.9% (95% CI: 88.9-93), respectively. Twenty-three patients (2.9%)
      presented locoregional recurrences. Most of them presented aggressive biological
      features with grade III tumors in 17 patients (74%) with high mitotic index in 16
      cases (70%) and triple negative tumors in 12 (52%). Lymphovascular invasion (LVI)
      was observed in 11 cases (48%). In 14 cases the locoregional recurrences were
      diagnosed at the same time as the metastatic disease whereas 4 patients presented
      distant metastases secondarily. Local (Chest wall) recurrences occurred in 13
      cases (56%) with the coverage by the isodose of 47.5 Gy (isodose 95%). Fifteen
      regional recurrences (lymph nodes) were observed in 13 patients. Only 3 regional
      recurrences occurred within irradiated volumes and 12 regional recurrences
      occurred outside irradiated areas. Conclusion: In presented series, the local
      recurrences were related mostly to the tumor biological aggressivity and radio
      resistance. Small number was caused by geographical miss. Further follow-up and
      careful registration of the recurrences is needed to improve their understanding.

PMID- 29594208
TI  - Anemia, leukocytosis and thrombocytosis as prognostic factors in patients with
      cervical cancer treated with radical chemoradiotherapy: A retrospective cohort
      study.
AB  - Introduction: Anemia has long been associated with poor prognosis in patients
      with cervical cancer. Recently, additional hematologic parameters have emerged as
      potential indicators of worse outcome in this patient group. In a cohort of
      cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy,
      we report on the prognostic significance of hematologic parameters including
      anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis,
      the effect of combining anemia with other hematologic parameters, and the effect
      of changes in hemoglobin levels during treatment. Materials and methods: Two
      hundred fifty-seven cervical cancer patients were retrospectively identified from
      a single cancer institution's database. Hematologic parameters were categorized
      as: anemia (hemoglobin <=115 g/L), leukocytosis (white blood cell count >10 *
      109/L), thrombocytosis (platelets >400 * 109/L), and NLR (ratio >5). The
      association between clinical factors and hematologic parameters on progression
      free survival (PFS) and overall survival (OS) were assessed at 5 years. Results:
      At 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p < 0.0001; OS: 68% vs
      41%, p < 0.0001) and on-treatment anemia (PFS: 62% vs 40%, p < 0.0001; OS: 70% vs
      48%, p < 0.0001) were significantly associated with worse survival. This adverse
      effect on 5-year PFS and OS was increased in patients with both pre-treatment
      anemia and leukocytosis (PFS: 72% vs 42%, p < 0.0001; OS: 68% vs 37%, p < 0.0001)
      and pre-treatment anemia and elevated NLR (PFS: 61% vs 30%, p < 0.0001; OS: 68%
      vs 37%, p < 0.0001). Five-year PFS (50% vs 31%) and OS (60% vs 36%) was better in
      patients whose pre-treatment anemia improved to normal hemoglobin levels on
      treatment vs those patients who were anemic both pre- and on-treatment.
      Conclusion: Pre-treatment and on-treatment anemia were significant, independent
      predictors of worse PFS and OS. Anemia and other hematologic parameters remain
      prognostic markers for cervical cancer patients. Improvement in PFS and OS was
      seen in patients with normalization of hemoglobin.

PMID- 29594209
TI  - Assessment of pulmonary 18F-FDG-PET uptake and cytokine profiles in non-small
      cell lung cancer patients treated with radiotherapy and erlotinib.
AB  - Purpose: To investigate effects of radiotherapy (RT) and erlotinib on pulmonary
      glucose uptake using 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission
      tomography (PET) during and after treatment of non-small cell lung cancer (NSCLC)
      and to identify associations between serum cytokine levels and lung glucose
      uptake. Material and methods: Twenty-seven patients with advanced NSCLC,
      receiving RT alone or concomitant RT and erlotinib therapy, were examined by 18F
      FDG PET before, during, and after treatment. A total of 57 18F-FDG PET scans were
      analyzed. Pulmonary 18F-FDG uptake and radiotherapy dose mapping were used to
      acquire dose-response curves for each patient, where subsequent linear regression
      gave a glucose uptake level in the un-irradiated parts of the lungs (SUV0) and a
      response slope (DeltaSUV). Serum cytokine levels at corresponding time points
      were assessed using a multiplex bioassay. Correlations between the most robust
      cytokines and lung 18F-FDG dose response parameters were further investigated.
      Results: From the dose response analysis, SUV0 at post-therapy was significantly
      higher (P < 0.001) than at mid- and pre-therapy (45% and 58%, respectively) for
      the group receiving RT + erlotinib. Also, SUV0 at post-therapy was higher for
      patients receiving RT + erlotinib compared to RT alone (42%; P < 0.001). No
      differences in DeltaSUV were seen with treatments or time. SUV0 was positively
      associated (r = 0.47, P = 0.01) with serum levels of the chemokine C-C motif
      ligand 21 (CCL21) for patients receiving RT + erlotinib. Conclusions: Concomitant
      RT and erlotinib causes an elevation in pulmonary 18F-FDG uptake post treatment
      compared to RT alone. Pulmonary glucose uptake is associated with an upregulation
      of a chemokine (CCL21) involved in inflammatory reactions.

PMID- 29594210
TI  - Barriers to radiotherapy access at the University College Hospital in Ibadan,
      Nigeria.
AB  - Introduction: Nigeria has the biggest gap between radiotherapy availability and
      need, with one machine per 19.4 million people, compared to one machine per
      250,000 people in high-income countries. This study aims to identify its patient
      level barriers to radiotherapy access. Material and methods: This was a cross
      sectional study consisting of patient questionnaires (n = 50) conducted in
      January 2016 to assess patient demographics, types of cancers seen, barriers to
      receiving radiotherapy, health beliefs and practices, and factors leading to
      treatment delay. Results: Eighty percent of patients could not afford
      radiotherapy without financial assistance and only 6% of the patients had federal
      insurance, which did not cover radiotherapy services. Of the patients who had
      completed radiotherapy treatment, 91.3% had experienced treatment delay or often
      cancellation due to healthcare worker strike, power failure, machine breakdown,
      or prolonged wait time. The timeliness of a patient's radiotherapy care
      correlated with their employment status and distance from radiotherapy center (p
      < 0.05). Conclusions: Barriers to care at a radiotherapy center in a low- and
      middle-income country (LMIC) have previously not been well characterized. These
      findings can be used to inform efforts to expand the availability of radiotherapy
      and improve current treatment capacity in Nigeria and in other LMICs.

PMID- 29594211
TI  - P4HA1: A single-gene surrogate of hypoxia signatures in oral squamous cell
      carcinoma patients.
AB  - Background and purpose: Hypoxia gene expression signatures are of high prognostic
      value for head and neck cancer patients. Recently, the prognostic information of
      a multiple-gene hypoxia signature was found to be provided by the mRNA level of
      P4HA1 alone (Tawk et al., 2016). Therefore, we studied the prognostic value of
      P4HA1 in an independent cohort of oral squamous cell carcinoma (OSCC) patients.
      Material and methods: Frozen tumor samples of 118 adult OSCC patients were
      analysed for P4HA1 mRNA level by quantitative real-time TaqManTM PCR analysis.
      Kaplan-Meier analysis and Cox's regression analysis were performed to
      characterize the prognostic impact of P4HA1 mRNA level in OSCC patients. Results:
      The analyzed patient cohort was divided into four subgroups according to the
      quartiles of the P4HA1 mRNA levels. The highest intratumoral P4HA1 mRNA level was
      significantly correlated with a poor overall survival (RR = 2.2; P = 0.04) and an
      increased risk of locoregional recurrence (RR = 4.8; P = 0.02). In patients who
      received radiotherapy (n = 82) highest intratumoral P4HA1 mRNA level was
      significantly correlated with a poor overall survival (RR = 3.4; P = 0.01) and an
      increased risk of locoregional recurrence (RR = 10.3; P = 0.005). Moreover,
      significant correlations between the P4HA1 mRNA level and the mRNA level of
      several EMT and stem cell markers were found. Conclusions: A high P4HA1 mRNA
      level, as a single-gene surrogate of hypoxia, is an independent prognostic marker
      for the overall survival and locoregional recurrence of OSCC patients.

PMID- 29594212
TI  - Cell-line dependent effects of hypoxia prior to irradiation in squamous cell
      carcinoma lines.
AB  - Purpose: To assess the impact of hypoxia exposure on cellular radiation
      sensitivity and survival of tumor cells with diverse intrinsic radiation
      sensitivity under normoxic conditions. Materials and methods: Three squamous cell
      carcinoma (SCC) cell lines, with pronounced differences in radiation sensitivity,
      were exposed to hypoxia prior, during or post irradiation. Cells were seeded in
      parallel for colony formation assay (CFA) and stained for gammaH2AX foci or
      processed for western blot analysis. Results: Hypoxia during irradiation led to
      increased cellular survival and reduced amount of residual gammaH2AX foci in all
      the cell lines with similar oxygen enhancement ratios (OER SKX: 2.31, FaDu: 2.44,
      UT-SCC5: 2.32), while post-irradiation hypoxia did not alter CFA nor residual
      gammaH2AX foci. Interestingly, prolonged exposure to hypoxia prior to irradiation
      resulted in differential outcome, assessed as Hypoxia modifying factor (HMF)
      namely radiosensitization (SKX HMF: 0.76), radioresistance (FaDu HMF: 1.54) and
      no effect (UT SCC-5 HMF: 1.1). Notably, radiosensitization was observed in the
      ATM-deficient SKX cell line while UT SCC-5 and to a lesser extent also FaDu cells
      showed radiation- and hypoxia-induced upregulation of ATM phosphorylation. Across
      all the cell lines Rad51 was downregulated whereas phosphor-DNA-PKcs was enhanced
      under hypoxia for FaDu and UTSCC-5 and was delayed in the SKX cell line.
      Conclusion: We herein report a key role of ATM in the cellular fitness of cells
      exposed to prolonged moderate hypoxia prior to irradiation. While DNA damage
      response post-irradiation seem to be mainly driven by non-homologous end joining
      repair pathway in these conditions, our data suggest an important role for ATM
      kinase in hypoxia-driven modification of radiation response.

PMID- 29594213
TI  - Survival and failure types after radiation therapy of vulvar cancer.
AB  - Background and purpose: Describe the survival rates and distribution of events on
      competing failure types in vulvar carcinoma after treatment with chemoradiation
      (CRT) or radiation (RT) alone. Material and methods: We included patients with
      vulvar carcinoma treated with CRT or RT between 2009 and 2014. Survival was
      estimated using the Kaplan-Meier method. We performed a competing risk analysis
      and included five competing events: loco-regional failure (LRF), distant
      metastasis, LRF plus distant metastasis, and death without evidence of disease,
      with the remaining patients denoted alive without evidence of disease. Results:
      87 patients were treated. Progression free survival (PFS) and overall survival
      (OS) at 3 years were 40% and 57%, respectively. 41.3% of patients relapsed, most
      often loco-regionally. We saw significantly worse PFS and OS for patients older
      than 68 (p = 0.011/p = 0.010) and for patients treated with definitive RT (p =
      0.004/p = 0.005). Competing risk analysis showed increased risk of LRF, and that
      death was most often related to vulvar cancer. Death without disease recurrence
      was less frequent, even in the elderly. Conclusions: LRF was the most common
      event. PFS and OS were inferior for elderly patients and patients treated
      definitively. A better understanding of these differences may be used to define
      risk adapted treatment strategies.

PMID- 29594215
TI  - Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic
      ablative radiotherapy for medically inoperable stage I non-small cell lung
      cancer.
AB  - Purpose: In this single institution retrospective study of patients with stage I
      medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic
      ablative radiotherapy (SABR) we attempt to model overall survival (OS) using
      initial prognostic variables with specific attention on the Charlson co-morbidity
      index (CCI). Methods: Between 2008 and 2013, 335 patients with medically
      inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy
      (50-60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution.
      Medical comorbidities and Charlson scores were determined by individual chart
      review. Patients were stratified into 3 groups based on the CCI score (0-1, 2-3,
      4-9) and again based on the age-adjusted Charlson Comorbidity score (aCCI).
      Cumulative survival for each stratum was determined using the Kaplan-Meier
      method. Non-significant and confounding variables were identified and discounted
      from survival modeling. 3 sex stratified Cox regression models were tested: (1)
      aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone,
      comorbidity removed. Results: The median survival was 4.4 years and the median
      follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively.
      Patients with aCCI 7-12 had an increased hazard of death on univariate analysis
      HR 2.45 (1.15-5.22 95%CI, p = 0.02) and -excluding age as a competing variable-
      on multivariate analysis HR 2.25 (1.04-4.84 95%CI, p = 0.04). Patients with CCI 4
      9 had an increased hazard of death on univariate analysis HR 1.57(1.30-2.90) but
      not on multivariate analysis. On formalized testing - with either continuous or
      categorical variables- all three survival models yielded similar coefficients of
      effect. Conclusion: We identify male gender, weight loss greater than 10% and age
      as independent prognostic factors for patients treated with medically inoperable
      NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival
      models, age alone can be used interchangeably with aCCI or CCI plus age with the
      same prognostic value. Age is more reliably recorded, less prone to error and
      therefore a more useful metric than Charlson score in this group of patients.

PMID- 29594214
TI  - SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative
      radiochemotherapy.
AB  - Introduction: Outcome after postoperative radiochemotherapy (RT-CT) for patients
      with advanced head and neck squamous cell carcinomas (HNSCC) remains
      unsatisfactory, especially among those with HPV negative tumours. Therefore, new
      biomarkers are needed to further define subgroups for individualised therapeutic
      approaches. Preclinical and first clinical observations showed that the chemokine
      receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour
      cell proliferation, survival, cancer progression, metastasis and treatment
      resistance. However, the data on the prognostic value of SDF-1/CXCR4 expression
      for HNSCC are conflicting. The aim of our hypothesis-generating study was to
      retrospectively explore the prognostic potential of SDF-1/CXCR4 in a well-defined
      cohort of HNSCC patients collected within the multicenter biomarker study of the
      German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Material and
      methods: Patients with stage III and IVA HNSCC of the oral cavity, oropharynx and
      hypopharynx were treated with resection and adjuvant radiotherapy (RT) with >=60
      Gy and concurrent cisplatin-based chemotherapy (CT). Tissue micro-arrays (TMAs)
      from a total of 221 patients were generated from surgical specimens, 201
      evaluated for the SDF-1 and CXCR4 expression by immunofluorescence and correlated
      with clinico-pathological and outcome data. Results: In univariate and
      multivariate analyses intracellular SDF-1 expression was associated with lower
      loco-regional control (LRC) in the entire patient group as well as in the HPV16
      DNA negative subgroup. CXCR4 expression showed a trend for lower LRC in the
      univariate analysis which was not confirmed in the multivariate analysis. Neither
      for SDF-1 nor CXCR4 expression associations with distant metastasis free or
      overall survival were found. Conclusions: Our exploratory data support the
      hypothesis that overexpression of intracellular SDF-1 is an independent negative
      prognostic biomarker for LRC after postoperative RT-CT in high-risk HNSCC.
      Prospective validation is warranted and further exploration of SDF-1/CXCR4 as a
      potential therapeutic target to overcome treatment resistance in HNSCC appears
      promising.

PMID- 29594216
TI  - A predictive model for residual disease after (chemo) radiotherapy in
      oropharyngeal carcinoma: Combined radiological and clinical evaluation of tumor
      response.
AB  - Background and purpose: Early detection of Residual disease (RD) is vital for
      salvage possibilities after (chemo) radiatiotherapy for oropharyngeal carcinoma
      (OPC). We standardized clinical investigation to test its added value to MRI
      response evaluation and investigated the benefit of FDG-PET/CT. Materials and
      methods: Radiological response evaluation using Ojiri-score was done for 234
      patients with OPC, using MRI 12 weeks after (chemo) radiotherapy between 2010 and
      2014. The presence of mucosal lesions and/or major complaints (still completely
      tube feeding-dependent and/or opiate-dependent because of swallowing problems)
      was scored as clinical suspicion (CS). Retrospectively, the performance of Ojiri
      to predict RD was compared to CS and both combined using Pearson Chi-squared. Of
      the whole group, FDG-PET/CT metabolic response (MR) was available in 50 patients.
      Results: Twelve out of 234 patients (5.1%) had RD. Ojiri and CS had excellent
      negative predictive value (NPV) (98% and 100% respectively). The combination of
      CS and Ojiri reduced false positives by 32% (38-26 patients) without lowering NPV
      (98%). No patients with complete MR (n = 39) at the FDG-PET/CT had RD compared to
      5 (45%) with partial MR. Conclusion: For response evaluation in OPC, the
      combination of CS and Ojiri-score improved the predictive accuracy by reducing
      false positives compared to them individually. FDG-PET/CT is promising to further
      reduce false positives.

PMID- 29594217
TI  - Treatment constraints for single dose external beam preoperative partial breast
      irradiation in early-stage breast cancer.
AB  - Background: Following breast-conserving surgery and post-operative 3D-conformal
      accelerated partial breast irradiation (APBI), suboptimal cosmetic results have
      been reported. Preoperative radiation delivery to the intact tumor enables better
      target visualization and treatment volume reduction. Single dose preoperative
      APBI has the potential to improve toxicity profiles, reduce treatment burden and
      enable in vivo exploration of breast cancer radiogenomics. Purpose: Develop
      practical guidelines for single dose external beam preoperative APBI. Methods:
      Recommended dose constraints were derived from pooled dosimetry estimates from 2
      clinical trials. In an American dose escalation trial, a uniform 15, 18 or 21 Gy
      dose has previously been evaluated for non-lobular cT1N0 or low/intermediate
      grade DCIS <2 cm in prone position (n = 32). In the Netherlands, the feasibility
      of ablative APBI (20 Gy to GTV, 15 Gy to CTV) to non-lobular cT1N0 in supine
      position, is currently being explored (n = 15). The dosimetric adherence to the
      developed constraints was evaluated in new APBI plans with a 21 Gy uniform dose
      but an extended CTV margin (n = 32). Results: Dosimetric data pooling enabled the
      development of practical guidelines for single dose preoperative APBI.
      Conclusion: The developed guidelines will allow further explorations in the
      promising field of single dose preoperative external beam APBI for breast cancer
      treatment.

PMID- 29594218
TI  - The predictive value of nadir neutrophil count during treatment of cervical
      cancer: Interactions with tumor hypoxia and interstitial fluid pressure (IFP).
AB  - Background and purpose: Hypoxia, high interstitial fluid pressure (IFP) and
      immune effects have individually been shown to modulate radiotherapy (RT)
      response in cervical cancer. The aim of this study was to investigate the
      interplay between hypoxia or IFP and circulating neutrophil levels, and their
      combined effect on survival following RT. Material and methods: A total of 287
      FIGO stage IB to IIIB cervical cancer patients treated with RT or RT and
      cisplatin (RTCT) were included. Tumor hypoxia and IFP were measured at baseline
      prior to treatment. Absolute neutrophil count (ANC) was measured at baseline and
      weekly during treatment. Median follow up was 7.1 years. Results: High nadir ANC
      at the point of maximal myelosuppression was a stronger predictor of inferior
      survival than high baseline ANC after adjusting for clinical prognostic factors
      and treatment (RT vs. RTCT). The predictive effect of nadir ANC was most evident
      in patients with well-oxygenated tumors or tumors with high IFP at diagnosis.
      Conclusions: This study provides new information about the combined influence of
      the tumor microenvironment and myeloid cells on the survival of cervical cancer
      patients treated with RT/RTCT to motivate the development of new treatments based
      on molecular targeting of immune-based radioresistance pathways.

PMID- 29594219
TI  - Feasibility of stereotactic body radiotherapy for locally-advanced non-small cell
      lung cancer.
AB  - SBRT was feasible for approximately half of the locally-advanced NSCLC patients
      we assessed and for these patients has the potential to reduce a 30 fraction
      course to 12 fractions. Using SBRT in this setting requires compromises in
      techniques and further compromises may allow SBRT in a greater proportion of
      patients.

PMID- 29594220
TI  - Role of radiotherapy in extracranial metastatic malignant melanoma in the modern
      era.
AB  - Background: To assess the role of radiotherapy in metastatic malignant melanoma
      (MM) patients in modern era. Materials and methods: This is a retrospective study
      of MM patients treated with radiotherapy at Mayo Clinic from 1999 to 2014.
      Patients with pre- and post-treatment imaging studies (CT, MRI, and/or PET/CT)
      were assessed for metastasis failure (MF), regional/distant failure, and overall
      survival (OS). Results: In 75 MM patients, 56 and 68 lesions were treated with
      conventional/hypofractionated radiotherapy (CHRT) and stereotactic body
      radiotherapy (SBRT), respectively. The median doses for CHRT and SBRT were 30 Gy
      and 50 Gy, respectively. 1-year MF was 17% (SBRT 6% vs CHRT 31%, p < 0.01). 1
      year regional (5% vs 29%, p < 0.01) and distant progression (75% vs 89%, p <
      0.01) were improved with SBRT. Median OS was 15.6 months (CHRT 7.0 vs SBRT 22.9,
      p < 0.01). Prognostic factors for OS included age <=55 years (RR 0.25),
      oligometastatic disease (RR 0.34), SBRT (RR 0.38) and treating all lesions (RR
      0.28, all p < 0.01). Conclusions: SBRT for extracranial MM exhibited improved MF
      compared with CHRT, consistent with intracranial radiosurgery data. Though these
      data are retrospective and subject to selection bias, our findings support the
      prudent use of SBRT in a select group of favorable, oligometastatic MM patients,
      and should be discussed as an alternative to surgery and ablation.

PMID- 29594221
TI  - Correlation between urinary dose and delayed radiation cystitis after 78 Gy
      intensity-modulated radiotherapy for high-risk prostate cancer: A 10-year follow
      up study of genitourinary toxicity in clinical practice.
AB  - Purpose: To investigate the factors associated with the risk of long-term
      genitourinary (GU) toxicity among high-risk prostate cancer (PC) patients treated
      with high-dose intensity-modulated radiotherapy (IMRT). Methods and materials:
      Between 2000 and 2011, PC patients treated with 78 Gy in 39 fractions delivered
      by IMRT combined with neo-adjuvant hormonal therapy were selected from among our
      database. GU toxicities and clinical factors, as well as separate anatomical
      urinary structures, were evaluated in terms of their associations. Results: A
      total of 309 patients was included in this study. The median follow-up was 104
      months (range: 24-143 months). The most frequently observed late grade >=2 GU
      toxicity was hematuria (11.2%: 10-year actuarial risk) with radiation cystitis
      observed in the majority of patients. In univariate analysis, late grade >=2
      hematuria was associated with the exposure to doses >75 Gy (V75) of the bladder
      neck and V70 of the bladder wall, as well as with T stage. V75 of the bladder
      neck remained significant in multivariate analysis (p = 0.049). Conclusions: At
      the 10-year follow up of high-dose IMRT, a major concern was proved to be delayed
      cystitis related to the higher volume of bladder neck dose exposed excess over 75
      Gy.

PMID- 29594223
TI  - Late cutaneous effects of a local potent steroid during adjuvant radiotherapy for
      breast cancer.
AB  - Purpose: The aim of this study was to evaluate whether treatment with a local
      potent corticosteroid during adjuvant external radiotherapy (ERT) of breast
      cancer is associated with late skin toxicity. Material and methods: Sixty
      patients (32 treated with potent corticoid cream versus 28 controls treated with
      moisturizer) who had been included in a randomized study on prophylactic local
      corticosteroid treatment under adjuvant ERT in 2009 and 2010 were subjected to a
      follow-up study in 2016.Assessments of skin texture were registered according to
      the Late Radiation Morbidity Scoring Scheme (RTOG). Dryness, skin colour and skin
      thickness were objectively measured using non-invasive instruments. The patients
      were assessed for differences between their treated and untreated breasts.
      Results: Skin atrophy was not noticed in any of the 60 patients. Objective
      instrumental measurements did not reveal any significant differences in skin
      dryness, colour, pigmentation or skin thickness over the average follow-up time
      of six years. Clinical assessment based on the RTOG scoring system revealed that
      the odds ratio of having late skin problems in patients treated with moisturizer
      compared to patients treated with corticosteroid was 3.2 (95% CI: 1.0
      10.1).Patients reported minor cosmetic dermatological sequelae. Seven patients
      developed telangiectasia, which caused cosmetic inconvenience. Conclusion: In
      this study, prophylactic corticosteroid treatment to ameliorate radiation
      dermatitis during adjuvant ERT of breast cancer was not associated with an
      increase in late skin toxicity nor did it result in skin atrophy. This study is
      limited by its small sample size, and the risk for false positive findings.

PMID- 29594222
TI  - The impact of the IGF-1 system of cancer cells on radiation response - An in
      vitro study.
AB  - Background: Overexpression of the insulin-like growth factor-1 receptor (IGF-1R)
      is associated with increased cell proliferation, differentiation, transformation,
      and tumorigenicity. Additionally, signaling involved in the resistance of cancer
      cells to radiotherapy originates from IGF-1R. The purpose of this study was to
      investigate the role of the IGF-1 system in the radiation response and further
      evaluate its effect on the expression of DNA repair pathway genes. Methods: To
      inhibit the IGF-1 system, we stably transfected the Caco-2 cell line to express a
      kinase-deficient IGF-1R mutant. We then studied the effects of this mutation on
      cell growth, the response to radiation, and clonogenic survival, as well as using
      a cell viability assay to examine DNA damage and repair. Finally, we performed
      immunofluorescence for gamma-H2AX to examine double-strand DNA breaks and
      evaluated the expression of 84 key genes involved in DNA repair with a real-time
      PCR array. Results: Mutant IGF-1R cells exhibited significantly blunted cell
      growth and viability, compared to wild-type cells, as well as reduced clonogenic
      survival after gamma-irradiation. However, mutant IGF-1R cells did not show any
      significant delays in the repair of radiation-induced DNA double-strand breaks.
      Furthermore, expression of mutant IGF-1R significantly down-regulated the mRNA
      levels of BRCA2, a major protein involved in homologous recombination DNA repair.
      Conclusion: These results indicate that blocking the IGF-1R-mediated signaling
      cascade, through the expression of a kinase-deficient IGF-1R mutant, reduces cell
      growth and sensitizes cancer cells to ionizing radiation. Therefore, the IGF-1R
      system could be a potential target to enhance radio-sensitivity and the efficacy
      of cancer treatments.

PMID- 29594224
TI  - Prospective analysis of in vivo landmark point-based MRI geometric distortion in
      head and neck cancer patients scanned in immobilized radiation treatment
      position: Results of a prospective quality assurance protocol.
AB  - Purpose: Uncertainties related to geometric distortion are a major obstacle for
      effectively utilizing MRI in radiation oncology. We aim to quantify the geometric
      distortion in patient images by comparing their in-treatment position MRIs with
      the corresponding planning CTs, using CT as the non-distorted gold standard.
      Methods: Twenty-one head and neck cancer patients were imaged with MRI as part of
      a prospective Institutional Review Board approved study. MR images were acquired
      with a T2 SE sequence (0.5 * 0.5 * 2.5 mm voxel size) in the same immobilization
      position as in the CTs. MRI to CT rigid registration was then done and geometric
      distortion comparison was assessed by measuring the corresponding anatomical
      landmarks on both the MRI and the CT images. Several landmark measurements were
      obtained including; skin to skin (STS), bone to bone, and soft tissue to soft
      tissue at specific levels in horizontal and vertical planes of both scans. Inter
      observer variability was assessed and interclass correlation (ICC) was
      calculated. Results: A total of 430 landmark measurements were obtained. The
      median distortion for all landmarks in all scans was 1.06 mm (IQR 0.6-1.98). For
      each patient 48% of the measurements were done in the right-left direction and
      52% were done in the anteroposterior direction. The measured geometric distortion
      was not statistically different in the right-left direction compared to the
      anteroposterior direction (1.5 +/- 1.6 vs. 1.6 +/- 1.7 mm, respectively, p =
      0.4). The magnitude of distortion was higher in the STS peripheral landmarks
      compared to the more central landmarks (2.0 +/- 1.9 vs. 1.2 +/- 1.3 mm, p <
      0.0001). The mean distortion measured by observer one was not significantly
      different compared to observer 2, 3, and 4 (1.05, 1.23, 1.06 and 1.05 mm,
      respectively, p = 0.4) with ICC = 0.84. Conclusion: MRI geometric distortions
      were quantified in radiotherapy planning applications with a clinically
      insignificant error of less than 2 mm compared to the gold standard CT.

PMID- 29594225
TI  - Retrospective methods to estimate radiation dose at the site of breast cancer
      development after Hodgkin lymphoma radiotherapy.
AB  - Background: An increased risk of breast cancer following radiotherapy for Hodgkin
      lymphoma (HL) has now been robustly established. In order to estimate the dose
      response relationship more accurately, and to aid clinical decision making, a
      retrospective estimation of the radiation dose delivered to the site of the
      subsequent breast cancer is required. Methods: For 174 Dutch and 170 UK female
      patients with breast cancer following HL treatment, the 3-dimensional position of
      the breast cancer in the affected breast was determined and transferred onto a CT
      based anthropomorphic phantom. Using a radiotherapy treatment planning system the
      dose distribution on the CT-based phantom was calculated for the 46 different
      radiation treatment field set-ups used in the study population. The estimated
      dose at the centre of the breast cancer, and a margin to reflect dose uncertainty
      were determined on the basis of the location of the tumour and the isodose lines
      from the treatment planning. We assessed inter-observer variation and for 47
      patients we compared the results with a previously applied dosimetry method.
      Results: The estimated median point dose at the centre of the breast cancer
      location was 29.75 Gy (IQR 5.8-37.2), or about 75% of the prescribed radiotherapy
      dose. The median dose uncertainty range was 5.97 Gy. We observed an excellent
      inter-observer variation (ICC 0.89 (95% CI: 0.74-0.95)). The absolute agreement
      intra-class correlation coefficient (ICC) for inter-method variation was 0.59
      (95% CI: 0.37-0.75), indicating (nearly) good agreement. There were no systematic
      differences in the dose estimates between observers or methods. Conclusion:
      Estimates of the dose at the point of a subsequent breast cancer show good
      correlation between methods, but the retrospective nature of the estimates means
      that there is always some uncertainty to be accounted for.

PMID- 29594226
TI  - Prognostic impact of leukocyte counts before and during radiotherapy for
      oropharyngeal cancer.
AB  - Introduction: Peripheral blood count components are accessible and evidently
      predictive in other cancers but have not been explored in oropharyngeal
      carcinoma. We examine if there is an association between the use of intensity
      modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) and
      lymphopenia, as well as if there is an association between baseline neutrophilia,
      baseline leukocytosis and lymphocyte nadir in oropharyngeal cancer. Materials and
      Methods: Analysis started with 150 patients from a previous case to case study
      design, which retrospectively identified adults with oropharyngeal carcinoma, 100
      treated with IMRT in 2010-2012 and 50 treated with IMPT in 2011-2014.
      Pretreatment leukocyte, neutrophil, lymphocyte, and hemoglobin levels were
      extracted, as were neutrophil and lymphocyte nadir levels during radiotherapy. We
      retained 137 patients with recorded pre-treatment leukocyte and neutrophil levels
      for associated analysis and 114 patients with recorded lymphocyte levels during
      radiation and associated analysis. Multivariate survival analyses were done with
      Cox regression. Results: The radiotherapy type (IMRT vs. IMPT) was not associated
      with lymphopenia (grade 3 P > .99; grade 4 P = .55). In univariate analyses, poor
      overall survival was associated with pretreatment neutrophilia (hazard ratio [HR]
      5.58, 95% confidence interval [CI] 1.99-15.7, P = .001), pretreatment
      leukocytosis (HR 4.85, 95% CI 1.73-13.6, P = .003), grade 4 lymphopenia during
      radiotherapy (HR 3.28, 95% CI 1.14-9.44, P = .03), and possibly smoking status
      >10 pack-years (HR 2.88, 95% CI 1.01-8.18, P = .05), but only T status was
      possibly significant in multivariate analysis (HR 2.64, 95% CI 0.99-7.00, P =
      .05). Poor progression-free survival was associated with pretreatment
      leukocytosis and T status in univariate analysis, and pretreatment neutrophilia
      and advanced age on multivariate analysis. Conclusions: Treatment modality did
      not affect blood counts during radiotherapy. Pretreatment neutrophilia,
      pretreatment leukocytosis, and grade 4 lymphopenia during radiotherapy were
      associated with worse outcomes after, but establishing causality will require
      additional work with increased statistical power.

PMID- 29594227
TI  - Sites of recurrent disease and prognostic factors in SCLC patients treated with
      radiochemotherapy.
AB  - Objectives: Concurrent radiochemotherapy (RCHT) is standard treatment in locally
      advanced small cell lung cancer (SCLC) patients. Due to conflicting results on
      elective nodal irradiation (ENI) or selective node irradiation (SNI) there is no
      clear evidence on optimal target volumes. Therefore, the purposes of this study
      were to assess the sites of recurrent disease in SCLC and to evaluate the
      feasibility of SNI versus ENI. Methods: A retrospective single-institution study
      of 43 consecutive patients treated with RCHT was performed. After state-of-the
      art staging including FDG-PET/CT, all patients underwent three-dimensional
      conformal radiotherapy to a total dose of 45 Gy in twice-daily fractions of 1.5
      Gy starting concurrently with the first or second chemotherapy cycle. All sites
      of loco-regional recurrences were correlated to the initial tumor and dose
      delivered. The impact of potential prognostic variables on outcome was evaluated
      using the Cox-regression model. Results: 13 patients (30%) relapsed locally or
      regionally: six within the initial primary tumor volume, five within the
      initially affected lymph nodes, one metachronously within primary tumor and
      initially affected lymph nodes, and one both inside and outside of the initial
      nodal disease. All sites of loco-regional recurrence had received 92-106% of the
      prescribed dose. Conclusion: In our study most recurrences occurred within the
      primary tumor or initially affected lymph nodes, or distantly. We did not
      register any case of isolated nodal failure, supporting the use of selective
      nodal irradiation, possibly with the addition of supraclavicular irradiation in
      patients with nodal disease in the upper mediastinum.

PMID- 29594228
TI  - VMAT radiation-induced nausea and vomiting in adjuvant breast cancer
      radiotherapy: The incidental effect of low-dose bath exposure.
AB  - Background and purpose: To investigate the hypothesis on low-dose bath exposure
      related to radiation-induced nausea and vomiting (RINV) in adjuvant breast
      volumetric modulated arch therapy (VMAT). Methods and materials: A total of 106
      consecutive breast cancer patients (pts) treated with adjuvant radiotherapy (RT)
      with VMAT from January 2013 to May 2016 were evaluated retrospectively. For each
      pt, a planning CT was reimported and the coeliac plexus and gastroesophageal
      junction with gastric mouth (GEJCPs) were contoured as a new organ at risk (OAR)
      in the upper abdominal area. RINV was associated with Dmax and Dmean to GEJCPs.
      Univariate analysis with chi2, t-test, and Pearson's covariance was used for
      statistical analysis. Results: Of 106 pts, 64% complained of acute RINV according
      to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. RINV
      was related to Dmax > 10 Gy and Dmean > 3 Gy to GEJCPs (P < 0.005). The radiation
      breast side and planning target volume (PTV) correlated with RINV. Conclusions:
      RINV in VMAT breast radiotherapy could be a new emerging acute side effect due to
      a low dose bath to upper abdominal structures such as the GEJCPs. A Dmax < 10 Gy
      and Dmean < 3 Gy to GEJCPs should be constrained in VMAT planning to minimize
      RINV risk in breast radiotherapy.

PMID- 29594229
TI  - Radiomic analysis in prediction of Human Papilloma Virus status.
AB  - Human Papilloma Virus (HPV) has been associated with oropharyngeal cancer
      prognosis. Traditionally the HPV status is tested through invasive lab test.
      Recently, the rapid development of statistical image analysis techniques has
      enabled precise quantitative analysis of medical images. The quantitative
      analysis of Computed Tomography (CT) provides a non-invasive way to assess HPV
      status for oropharynx cancer patients. We designed a statistical radiomics
      approach analyzing CT images to predict HPV status. Various radiomics features
      were extracted from CT scans, and analyzed using statistical feature selection
      and prediction methods. Our approach ranked the highest in the 2016 Medical Image
      Computing and Computer Assisted Intervention (MICCAI) grand challenge: Oropharynx
      Cancer (OPC) Radiomics Challenge, Human Papilloma Virus (HPV) Status Prediction.
      Further analysis on the most relevant radiomic features distinguishing HPV
      positive and negative subjects suggested that HPV positive patients usually have
      smaller and simpler tumors.

PMID- 29594230
TI  - Local control and overall survival after frameless radiosurgery: A single center
      experience.
AB  - Introduction: Stereotactic radiosurgery (SRS) has been increasingly advocated for
      1-3 small brain metastases. The goal of this study was to evaluate the clinical
      results in patients with brain metastases treated with LINAC-based SRS using a
      thermoplastic mask (non-invasive fixation system) and Image-Guided Radiotherapy
      (IGRT). Material and Methods: In this single-institution study 48 patients with
      77 brain metastases were treated between February 2012 and January 2014. The
      prescribed dose was 20 Gy or 18 Gy as a single fraction. SRS was performed with a
      True Beam STX Novalis Radiosurgery LINAC (Varian Medical Systems). The
      verification of positioning was done using the BrainLAB ExacTrac (r) X-ray 6D
      system and cone-beam CT. Results: In 69 of 77 treated brain metastases (90%) the
      follow-up was documented on MR imaging performed every 3 months. Mean follow-up
      time was 10.86 months. Estimated 1-year local control was 83%, using the Kaplan
      Meier method. In 7/69 brain metastases (10%) local failure (LF) was diagnosed.
      Median progression free survival (PFS) was 3.73 months, largely due to distant
      brain relapse. A GTV of <=2.0 cm3 was significantly associated with a better PFS
      than a GTV >2.0 cm3. Extracranial stable disease and GTV <=2.5 cm3 were
      significant predictors of OS.We observed 2 cases of radiation necrosis diagnosed
      by histology after surgical resection. No other cases of severe side effects
      (CTACE >= 3) were observed. Conclusion: LINAC-based frameless SRS with the
      BrainLAB Mask using the BrainLAB ExacTrac (r) X-ray 6D system for patient
      positioning is well tolerated, safe and leads to favorable crude local control of
      90%. In our experience, local control after frameless (ringless) SRS is as good
      as ring-based SRS reported in literature. Without invasive head fixation,
      radiotherapy is more comfortable for patients.

PMID- 29594231
TI  - Radiotherapy dose-distribution to the perirectal fat space (PRS) is related to
      gastrointestinal control-related complications.
AB  - Traditionally rectal symptoms following pelvic/prostate radiotherapy are
      correlated to the dosimetry of the anorectum or a substructure of this. It has
      been suggested that the perirectal fat space (PRS) surrounding the rectum may
      also be relevant. This study considers the delineation and dosimetry of the PRS
      related to both rectal bleeding and control-related toxicity. Initially, a case
      control cohort of 100 patients from the RADAR study were chosen based on
      presence/absence of rectal control-related toxicity. Automated contouring was
      developed to delineate the PRS. 79 of the 100 auto-segmentations were considered
      successful. Balanced case-control cohorts were defined from these cases. Atlas of
      Complication Incidence (ACI) were generated to relate the DVH of the PRS with
      specific rectal symptoms; rectal bleeding and control-related symptoms
      (LENT/SOM). ACI demonstrated that control-related symptoms were related to the
      dose distribution to the PRS which was confirmed with Wilcoxon rank sum test (p <
      0.05). To the authors knowledge this is the first study implicating the dose
      distribution to the PRS to the incidence of control-related symptoms of rectal
      toxicity.

PMID- 29594232
TI  - Increasing genomic instability during cancer therapy in a patient with Li
      Fraumeni syndrome.
AB  - Background: Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder
      characterized by germline mutations of the p53 tumor-suppressor gene. In response
      to DNA damage, p53 stimulates protective cellular processes including cell-cycle
      arrest and apoptosis to prevent aberrant cell proliferation. Current cancer
      therapies involve agents that damage DNA, which also affect non-cancerous
      hematopoietic stem/progenitor cells. Here, we report on a child with LFS who
      developed genomic instability during craniospinal irradiation for metastatic
      choroid plexus carcinoma (CPC). Case presentation: This previously healthy 4-year
      old boy presented with parieto-temporal brain tumor, diagnosed as CPC grade-3.
      Screening for cancer-predisposing syndrome revealed heterozygous p53 germline
      mutation, leading to LFS diagnosis. After tumour resection and systemic
      chemotherapy, entire craniospinal axis was irradiated due to leptomeningeal
      seeding, resulting in disease stabilization for nearly 12 months. Blood
      lymphocytes of LFS patient (p53-deficient) and age-matched tumor-children (p53
      proficient) were collected before, during and after craniospinal irradiation and
      compared with asymptomatic carriers for identical p53 mutation, not exposed to
      DNA-damaging treatment. In p53-deficient lymphocytes of LFS patient radiation
      induced DNA damage failed to induce cell-cycle arrest or apoptosis. Although DNA
      repair capacity was not impaired, p53-deficient blood lymphocytes of LFS patient
      showed significant accumulation of 53BP1-foci during and even several months
      after irradiation, reflecting persistent DNA damage. Electron microscopy revealed
      DNA abnormalities ranging from simple unrepaired lesions to chromosomal
      abnormalities. Metaphase spreads of p53-deficient lymphocytes explored by mFISH
      revealed high amounts of complex chromosomal aberrations after craniospinal
      irradiation. Conclusions: Tumor suppressor p53 plays a central role in
      maintaining genomic stability by promoting cell-cycle checkpoints and apoptosis.
      Here, we demonstrate that a patient with LFS receiving craniospinal irradiation
      including large volumes of bone marrow developed progressive genomic instability
      of the hematopoietic system. During DNA-damaging radiotherapy, genome-stabilizing
      mechanisms in proliferating stem/progenitor cells are perturbed by p53
      deficiency, increasing the risk of cancer initiation and progression.

PMID- 29594233
TI  - Uptake of Prostate-Specific Membrane Antigen (PSMA) in adenoid cystic carcinoma -
      Is PSMA-PET-CT a helpful tool in radiation oncology?
AB  - This case report shows the high PSMA-uptake in a patient with an adenoid cystic
      carcinoma of the maxillary sinus. Due to the intense ligand-uptake additional
      information for target volume delineation was obtained and the Treatment plan for
      bimodal radiotherapy with carbon ions was adapted accordingly.

PMID- 29594235
TI  - Radiotherapy for isolated granulocytic sarcoma: Case report and review of
      literature.
AB  - *Isolated chloroma should be considered as a systemic disease.*Consolidation
      radiotherapy has been related with prolonged failure free survival.*Excellent
      local control of chloroma is achieved with low-dose radiotherapy.

PMID- 29594234
TI  - Strong radioprotective FGF1 signaling down-regulates proliferative and metastatic
      capabilities of the angiosarcoma cell line, ISOS-1, through the dual inhibition
      of EGFR and VEGFR pathways.
AB  - Background and purpose: Angiosarcoma is associated with a poor prognosis and is
      treated with radiotherapy. Although FGF1 is a potential radioprotector, the
      influence of FGF1 on the malignancy of angiosarcoma remains unknown. Materials
      and methods: Highly stable FGF1 mutants, which exhibit stronger mitogenic
      activity than wild-type FGF1, were examined as strong radioprotectors and
      signaling agonists to clarify the effects of FGF1 on the murine angiosarcoma cell
      line ISOS-1. Results: FGF1 mutants reduced colony formation by and the in vitro
      invasion and migration of ISOS-1 cells, in addition to an increase in
      radiosensitivity to X-rays. In contrast, an FGFR inhibitor blocked the inhibitory
      effects of FGF1 mutants on colony formation, invasion, and migration. siRNA
      targeting the Fgfr1 gene showed that strong FGFR1 signaling reduced colony
      formation by ISOS-1 cells. However, the FGF1 mutant reduced the activation of
      VEGFRs and EGFRs in ISOS-1 cells more strongly than wild-type FGF1. Moreover, the
      inhibition of VEGFRs and EGFRs synergistically reduced colony formation by and
      invasion and migration of ISOS-1 cells. Conclusion: These results suggest that
      strong FGF1 signaling exerts not only radioprotective effects, but also
      inhibitory effects on proliferative and metastatic capacities of angiosarcoma
      through the dual inhibition of EGFR and VEGFR pathways.

PMID- 29594236
TI  - Treatment de-escalation for HPV-driven oropharyngeal cancer: Where do we stand?
AB  - HPV-driven oropharyngeal cancers have significantly better survival rates than
      tobacco and alcohol induced head and neck cancers. As HPV-positive patients are
      younger, healthier and far more likely to survive their disease, long-term
      treatment side effects are becoming a major issue. This has led the scientific
      and medical community to reassess the current treatment protocols in order to
      develop less toxic strategies while maintaining good oncological outcomes. In
      this article, we discuss the ongoing treatment de-escalation trials and highlight
      the issues raised by these studies.

PMID- 29594237
TI  - PARADIGM-2: Two parallel phase I studies of olaparib and radiotherapy or olaparib
      and radiotherapy plus temozolomide in patients with newly diagnosed glioblastoma,
      with treatment stratified by MGMT status.
AB  - Glioblastoma has a dismal prognosis and molecular targeted agents have failed to
      improve outcomes to date. PARADIGM-2 is a phase I dose escalation study
      evaluating olaparib plus radiotherapy +/- temozolomide in newly diagnosed
      glioblastoma, using MGMT methylation status to stratify patients and inform
      treatment schedules.

PMID- 29594238
TI  - Retrospective assessment of MRI-based volumetric changes of normal tissues in
      glioma patients following radio(chemo)therapy.
AB  - In glioma patients, linac-based photon beam irradiation is a widely applied
      therapy, which achieves highly conformal target volume coverage, but is also
      known to cause side-effects to adjacent areas of healthy tissue. Apart from
      subjective measures, such as quality of life assessment and neurocognitive
      function tests, objective methods to quantify tissue damage are needed to assess
      this impact. Magnetic resonance imaging (MRI) is a well-established method for
      brain tumor diagnoses as well as assessing treatment response. In this study, we
      retrospectively assessed volumetric changes of gray matter (GM) and white matter
      (WM) in glioma patients following photon irradiation using a heterogeneous MRI
      dataset obtained in routine clinical practice at different sites with imaging
      parameters and magnetic field strengths. We found a significant reduction in WM
      volume at one year [Formula: see text] and two years [Formula: see text] post
      radio(chemo)therapy whereas corresponding GM volumes did not change significantly
      ([Formula: see text] and [Formula: see text], respectively). More importantly, we
      also found large variations in the segmented tissue volumes caused by the
      heterogeneous MR data, thus potentially masking more subtle tissue changes over
      time. On the basis of these observations, we present suggestions regarding data
      acquisitions in future prospective MR studies to assess such volumetric changes.

PMID- 29594240
TI  - Skull base or cervical vertebral osteomyelitis following chemoradiotherapy for
      pharyngeal carcinoma: A serious but treatable complication.
AB  - Osteomyelitis, infection of the bone and marrow, following high dose (chemo
      )radiotherapy for head and neck cancer is uncommon and rarely seen in the
      cervical spine or temporal bone. Due to its proximity to critical structures,
      osteomyelitis in the latter regions could carry potentially important
      consequences. Furthermore, involvement near the skull base (e.g. temporal bone
      and high cervical vertebrae) presents unique challenges in diagnosis (especially
      in the differentiation from disease recurrence) and treatment, making early
      detection and timely intervention critical. In this report, we describe two cases
      of osteomyelitis, one involving the temporal bone and the other affecting the 2nd
      and 3rd cervical vertebrae, diagnosed and treated with good outcome in the
      setting of definitive chemoradiotherapy for locally advanced pharyngeal
      carcinomas. We suggest that for new or evolving post-radiotherapy osseous changes
      in regions that have received a high dose of radiotherapy, associated with
      unexpected and deteriorating spinal symptoms such as pain and spasm, radiation
      related osteomyelitis should be considered in the differential diagnosis from
      tumor progression. Timely referral to a surgical oncologist and infectious
      diseases specialist is paramount in achieving satisfactory clinical outcomes.

PMID- 29594239
TI  - The posterior cerebellum, a new organ at risk?
AB  - Eekers et al. have recently proposed a neuro-oncology atlas, which was co
      authored by most centers associated in the European Proton Therapy Network (EPTN;
      Figure 1). With the introduction of new treatment techniques, such as integrated
      magnetic resonance imaging and linear accelerators (MR-linac) or particle
      therapy, the prediction of clinical efficacy of these more costly treatment
      modalities becomes more relevant. One of the side-effects of brain irradiation,
      being cognitive decline, is one of the toxicities most difficult to measure and
      predict. In order to validly compare different treatment modalities, 1) a uniform
      nomenclature of the organs at risk (OARs), 2) uniform atlas-based delineation
      [e.g., Eekers et al.], 3) long-term follow-up data with standardized cognitive
      tests, 4) a large patient population, and 5) (thus derived) validated normal
      tissue complication probability (NTCP) models are mandatory. Apart from the Gondi
      model, in which the role of the dose to 40% of both hippocampi (HC) proves to be
      significantly related to cognition in 18 patients, no similar models are
      available. So there is a strong need for more NTCP models, on HC, brain tissue
      and possible other relevant brain structures. In this review we summarize the
      available evidence on the role of the posterior cerebellum as a possible new
      organ at risk for cognition, which is deemed relevant for irradiation of brain
      and head and neck tumors.

PMID- 29594241
TI  - SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain
      control in malignant pleural mesothelioma.
AB  - SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control
      in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative
      (20 Gy/5#) or dose escalated treatment (36 Gy/6#) will be delivered using
      advanced radiotherapy techniques and pain responses will be compared at week 5.
      Data will guide optimal palliative radiotherapy in MPM.

PMID- 29594242
TI  - FORECAST - A cloud-based personalized intelligent virtual coaching platform for
      the well-being of cancer patients.
AB  - Well-being of cancer patients and survivors is a challenge worldwide, considering
      the often chronic nature of the disease. Today, a large number of initiatives,
      products and services are available that aim to provide strategies to face the
      challenge of well-being in cancer patients; nevertheless the proposed solutions
      are often non-sustainable, costly, unavailable to those in need, and less well
      received by patients. These challenges were considered in designing FORECAST, a
      cloud-based personalized intelligent virtual coaching platform for improving the
      well-being of cancer patients. Personalized coaching for cancer patients focuses
      on physical, mental, and emotional concerns, which FORECAST is able to identify.
      Cancer patients can benefit from coaching that addresses their emotional
      problems, helps them focus on their goals, and supports them in coping with their
      disease-related stressors. Personalized coaching in FORECAST offers support,
      encouragement, motivation, confidence, and hope and is a valuable tool for the
      wellbeing of a patient.

PMID- 29594243
TI  - Resolution of atelectasis during radiochemotherapy of lung cancer with serious
      implications for further treatment. A case report.
AB  - Local failure is a major cause for low overall survival rates in advanced non
      small cell lung cancer (NSCLC). Among others, radioresistant tumor clones as well
      as geographical miss can explain these high local failure rates. One reason for
      geographical miss is a change of tumor related atelectasis in the course of
      radiotherapy. We present the case of a patient with UICC Stage IIIb NSCLC who
      presented with a large tumor related atelectasis. During definitive
      radiochemotherapy, the atelectasis resolved, which resulted in a massive tumor
      shift out of the planning target volume within 2 days. Without close monitoring
      by cone beam CTs and prompt replanning, this would have led to a geographical
      miss and relevant underdosage of the tumor. Furthermore, changes in anatomy and
      pulmonary function during treatment had implications for organs at risk and
      opened windows for dose escalation. We suggest at least biweekly CBCTs in
      patients with poststenotic atelectasis to ensure the rapid detection of
      geographical changes of the target and subsequent intervention if necessary.

PMID- 29594244
TI  - Combining radiotherapy and ipilimumab induces clinically relevant radiation
      induced abscopal effects in metastatic melanoma patients: A systematic review.
AB  - Background: In the last years, limited studies have described that radiotherapy
      could produce important distant responses in unirradiated sites, the so-called
      "abscopal effect". Recent evidence suggests that radiotherapy induces antigen
      release from tumor, in this way activating the immune system. However,
      radiotherapy alone is rarely enough to induce the systemic response requested for
      control of the metastases. With the advent of immunotherapy, the immune
      checkpoint inhibitors (ICI) have demonstrated impressive efficacy in various
      metastatic cancers. Currently, preclinical and clinical studies have reported a
      significant increase of abscopal responses in patients treated with the
      combination of radiotherapy and ICI. The purpose of this review was summarizing
      the clinical studies combining radiotherapy and ipilimumab (ipi), particularly
      focusing on abscopal responses. Methods and Materials: Databases of Medline (via
      Pubmed) from 2009 to June 2, 2017 were reviewed to obtain English language
      studies reporting clinical abscopal effect in the combination of radiotherapy
      with exclusive ipi in metastatic melanoma cancers. Included studies reported the
      abscopal effect as a primary endpoint, and as secondary endpoint included overall
      survival and toxicity. Results: A total of 16 studies met the inclusion criteria.
      These studies included a total of 451 patients, and in 5/16 studies the patients
      were treated on research protocols and followed-up prospectively. The median
      reported abscopal effect and OS were 26.5% and 19 months, respectively. The
      median toxicity >= Grade 3 was 18.3% ranged from 10% to 20%. Conclusion: Early
      clinical outcomes reports suggest that the combination of ipilimumab and RT may
      improve survival in metastatic melanoma patients. The abscopal responses become a
      clinically relevant effect of such combination and should be studied in
      controlled randomized trials.

PMID- 29594245
TI  - Definitive chemoradiotherapy with low-dose continuous 5-fluorouracil reduces
      hematological toxicity without compromising survival in esophageal squamous cell
      carcinoma patients.
AB  - Background and purpose: To compare chemoradiotherapy (CRT) with low-dose
      continuous 5-fluorouracil (5FU) to CRT with 5FU+cisplatin (CDDP) for esophageal
      squamous cell carcinoma (ESCC) in a retrospective cohort study. Methods and
      materials: We reviewed the cases of Stage I-IV ESCC patients who underwent
      definitive CRT in 2000-2014. Concomitant chemotherapy was one of the three
      regimens: (1) high-dose intermittent 5FU and CDDP (standard-dose FP: SDFP), (2)
      low-dose continuous 5FU and CDDP (LDFP), or (3) low-dose continuous 5FU (LD5FU).
      The general selection criteria for chemotherapy were: SDFP for patients aged <70
      yrs; LDFP for those aged 70-74 yrs; LD5FU for those aged >=75 yrs or with
      performance status (PS) >=3. Propensity scores were derived with chemotherapy
      (LD5FU vs. 5FU+CDDP) as the dependent variable. Results: In a multivariate
      analysis, chemotherapy (LD5FU vs. SDFP, p = .24; LDFP vs. SDFP, p = .52) did not
      affect the overall survival (OS). LD5FU caused significantly less grade 3-4
      leukopenia (9%) compared to SDFP (47%) and LDFP (44%) (p < .001). In a propensity
      matched analysis, LD5FU affected neither OS (HR 1.06; 95%CI 0.55-2.05; p = .87)
      nor progression-free survival (HR 0.95, 95%CI 0.50-1.81; p = .87). Conclusion:
      CRT with low-dose continuous 5FU may be a less toxic option for elderly ESCC
      patients.

PMID- 29594246
TI  - Surgery vs. primary radiotherapy in early-stage oropharyngeal cancer.
AB  - Background: Early-stage oropharyngeal squamous cell carcinoma (OPSCC) can
      currently be treated by surgical resection or definitive radiotherapy (RT). The
      aim of this study is to review the outcomes of early-stage OPSCC submitted to
      surgery or primary RT. Preliminary results have shown similar overall survival
      (OS) and locoregional recurrence-free survival (LRFS). Material/Methods:
      Retrospective study of patients with cT1-T2 cN0-N1 OPSCC, diagnosed between
      January 2009 and December 2014, treated with surgery or primary RT. Results: 61
      patients with cT1-T2 cN0-N1 OPSCC were included. Forty-two (69%) were submitted
      to surgical resection, of which 37 (88%) had adjuvant treatment (24 received RT
      and 13 chemoradiotherapy). Nineteen (31%) were treated with primary RT, and 3 of
      them had concurrent chemotherapy. RT was given with intensity-modulated radiation
      therapy (IMRT) (71%) or three-dimensional conformal radiation therapy (3D-CRT)
      (29%). At a median follow-up of 5.4 years, there were 3 tumor persistences, 5
      local failures, 2 regional failures and no distant metastasis. The 3-year and 5
      year OS were 77% and 71% in the RT group vs. 71% and 59% in the surgery group,
      respectively (HR 0.60, 95% CI 0.22-1.61; p = 0.30). The 3-year and 5-year LRFS
      were 71% and 64% in the RT group vs. 66% and 50% in the surgery group,
      respectively (HR 0.59, 95% CI 0.24-1.45; p = 0.24). Up to 34% had acute grade 3
      toxicity and 11% had grade 4 osteoradionecrosis of the jaw. Conclusions: Longer
      follow-up still does not show a significant difference in OS and LRFS between
      both treatments. Because most patients submitted to surgery required adjuvant RT
      and since its side-effects were not negligible, further studies are warranted to
      better suit the first treatment for each patient and to prevent the need for
      adjuvant treatment and the risk of toxicity.

PMID- 29594247
TI  - Do protons and X-rays induce cell-killing in human peripheral blood lymphocytes
      by different mechanisms?
AB  - Purpose: Significant progress has been made in the technological and physical
      aspects of dose delivery and distribution in proton therapy. However, mode of
      cell killing induced by protons is less understood in comparison with X-rays. The
      purpose of this study is to see if there is any difference in the mode of cell
      killing, induced by protons and X-rays in an ex vivo human peripheral blood
      lymphocyte (HPBL) model. Materials and methods: HPBL were irradiated with 60 MeV
      proton beam or 250-kVp X-rays in the dose range of 0.3-4.0 Gy. Frequency of
      apoptotic and necrotic cells was determined by the Fluorescein (FITC)-Annexin V
      labelling procedure, 1 and 4 h after irradiation. Chip-based DNA Ladder Assay was
      used to confirm radiation-induced apoptosis and necrosis. Chip-based DNA Ladder
      Assay was used to confirm radiation-induced apoptosis. Results: Ex vivo
      irradiation of HPBL with proton beams of 60 MeV or 250 kVp X-rays resulted in
      apoptotic as well as necrotic modes of cell-killing, which were evident at both 1
      and 4 h after irradiation in the whole dose and time range. Generally, our
      results indicated that protons cause relatively higher yields of cell death that
      appears to be necrosis compared to X-rays. The analysis also demonstrates that
      radiation type and dose play a critical role in mode of cell-killing. Conclusion:
      Obtained results suggest that X-rays and protons induce cell-killing by different
      modes. Such differences in cell-killing modes may have implications on the
      potential of a given therapeutic modality to cause immune modulation via
      programmed cell death (X-rays) or necrotic cell death (proton therapy). These
      studies point towards exploring for gene expression biomarkers related necrosis
      or apoptosis to predict immune response after proton therapy.

PMID- 29594248
TI  - Analysis of pseudoprogression after proton or photon therapy of 99 patients with
      low grade and anaplastic glioma.
AB  - Background and purpose: Proton therapy is increasingly used to treat primary
      brain tumors. There is concern for higher rates of pseudoprogression (PsP) after
      protons compared to photons. The purposes of this study are to compare the rate
      of PsP after proton vs. photon therapy for grade II and III gliomas and to
      identify factors associated with the development of PsP. Materials and methods:
      Ninety-nine patients age >18 years with grade II or III glioma treated with
      photons or protons were retrospectively reviewed. Demographic data, IDH and 1p19q
      status, and treatment factors were analyzed for association with PsP, progression
      free survival (PFS), and overall survival (OS). Results: Sixty-five patients were
      treated with photons and 34 with protons. Among those with oligodendroglioma, PsP
      developed in 6/42 photon-treated patients (14.3%) and 4/25 proton-treated
      patients (16%, p = 1.00). Among those with astrocytoma, PsP developed in 3/23
      photon-treated patients (13%) and 1/9 proton-treated patients (11.1%, p = 1.00).
      There was no difference in PsP rate based on radiation type, radiation dose,
      tumor grade, 1p19q codeletion, or IDH status. PsP occurred earlier in
      oligodendroglioma patients treated with protons compared to photons, 48 days vs.
      131 days, p < .01. On multivariate analyses, gross total resection (p = .03, HR =
      0.48, 95%CI = 0.25-0.93) and PsP (p = .04, HR = 0.22, 95% CI = 0.05-0.91) were
      associated with better PFS; IDH mutation was associated with better OS (p < .01,
      HR = 0.22, 95%CI = 0.08-0.65). Conclusions: Patients with oligodendroglioma but
      not astrocytoma develop PsP earlier after protons compared to photons. PsP was
      associated with better PFS.

PMID- 29594249
TI  - Relative biological effectiveness in proton beam therapy - Current knowledge and
      future challenges.

PMID- 29594250
TI  - Anti PD-L1 DUrvalumab combined with Cetuximab and RadiOtherapy in locally
      advanced squamous cell carcinoma of the head and neck: A phase I/II study
      (DUCRO).
AB  - Introduction and background: Head and neck squamous cell carcinoma (HNSCC) has
      been increasingly recognized as an immune suppressive malignancy. The efficacy of
      immune checkpoint inhibitors (ICI's) in the context of recurrent/metastatic (R/M)
      setting anticipates the possible integration of immunotherapy into the
      therapeutic armamentarium of locally advanced disease. Durvalumab (DUR) is a
      humanized monoclonal IgG1, anti-PD-L1 antibody with promising data in R/M HNSCC.
      The aim of our study is to test the antitumor activity of a combined regimen
      incorporating an immune checkpoint inhibitor into a conventional bio-radiation
      strategy for the cure of unfavorable locally advanced HNSCC. Methods/design: In
      this open label, multi-center, single-arm, phase I/II study, enrolled patients
      will receive Radiotherapy (RT) (69.9 Gy/2.12 Gy in 33 fractions) with concurrent
      Cetuximab (CTX) (400 mg/m2 1 week before RT start followed by 250 mg/m2 weekly)
      and DUR (fixed dose of 1500 mg every 4 weeks starting from RT-CTX week 1)
      followed by adjuvant DUR (to a maximum of 6 months after completion of RT-CTX).
      Primary endpoint of the study is 2-year progression-free survival (PFS). A safety
      run-in is planned after the enrollment of first 12, 24 and 36 patients. Patients
      affected by high-risk (>=N2a or >=T3, any N) larynx, hypopharynx and HPV negative
      oropharynx or HPV-positive oropharynx (>=T2, >=N2b, >=10 pack/years) will be
      eligible. Discussion: Conventional intensification strategies failed to provide
      any benefit for the cure of locally advanced HNSCC. For the still prevalent HPV
      negative population and the high risk-HPV positive disease, there is an unmet
      need for alternative treatment paradigms. Potentially, the inhibition of the PD
      1/PD-L1 checkpoint may synergize with both CTX and RT through immunologic
      interplay, ultimately aiming to reverse the HNSCC-induced immune suppression. The
      DUCRO study will seek to demonstrate if such a strategy may be safe and active.
      Trial registration: NCT number: NCT03051906Eudract number: 2016-004668-20.

PMID- 29594252
TI  - Learning radiation oncology in Europe: Results of the ESTRO multidisciplinary
      survey.
AB  - Introduction: Radiotherapy education can be very different across Europe, despite
      the publication of the ESTRO core curricula in 2011. The purpose of the current
      study is to map the different RO European education systems, to report their
      perceived quality and to understand what could be improved to better teach RO.
      Methods: An online survey consisting of 30 questions was sent to RO professionals
      under 40 years of age via email and social media. Clinicians, radiobiologists,
      physicists and radiation therapists (RTTs) were invited to answer questions
      regarding (1) demographics data, (2) duration, (3) organization, (4) content, (5)
      quality and potential improvements of national education programs. Results: Four
      hundred and sixty three questionnaires were received from 34 European countries.
      All disciplines were represented: 45% clinicians (n = 210), 29% physicists (n =
      135), 24% RTTs (n = 108) and 2% radiobiologists (n = 10). Male and female
      participants were well-balanced in each speciality, except for radiobiologists
      (80% males). Median age was 31.5 years old (range 21-40). A large range of the
      duration of the National RO education programs was observed: median = 9 years
      (range: 3-15). In half of the surveyed countries the European Credit Transfer
      System (ECTS), that facilitates mobility for trainees, has been implemented.
      Participants declared only a minority of countries have implemented the ESTRO
      Core Curriculum (n = 5). A quarter of participants indicated that their national
      education program is insufficient. Conclusion: This is the first study to examine
      the different RO education systems in Europe. Large differences in organization
      and duration of national education programs have been found, along with perceived
      quality across Europe within each speciality. These results show the necessity of
      a discussion on how to move forward in this diversity of education programs and
      the potential contribution that the ESTRO may fulfil.

PMID- 29594253
TI  - Improved outcome of treating locally advanced lung cancer with the use of Lattice
      Radiotherapy (LRT): A case report.
AB  - The Lattice Radiotherapy (LRT) technique is mainly based on the GRID technology
      with the improved feature of the 3D treatment delivery. A 72 year old male
      presented with left shoulder pain due to a 6 cm pulmonary mass in the left upper
      lobe (LUL) histologically proven Non-Small Cell Lung Cancer (NSCLC) stage IIIA.
      In July 2011 he was treated in our center with LRT followed by conventional
      fractionated Volumetric Modulated Arc Therapy (VMAT) combined with chemotherapy.
      Clinical and imaging follow up of 6 years demonstrated continued improvement and
      the patient is currently with no evidence of disease (NED). This outstanding
      result obtained in our first lung cancer patient treated with this approach
      corroborates its potential in the treatment of locally advanced lung cancer. In a
      period of 7 years we have treated more than 30 patients with LRT for different
      diagnosis and sites; 12 of them NSCLC patients, with markedly improved local
      control and minimal toxicity.

PMID- 29594251
TI  - The EMBRACE II study: The outcome and prospect of two decades of evolution within
      the GEC-ESTRO GYN working group and the EMBRACE studies.
AB  - The publication of the GEC-ESTRO recommendations one decade ago was a significant
      step forward for reaching international consensus on adaptive target definition
      and dose reporting in image guided adaptive brachytherapy (IGABT) in locally
      advanced cervical cancer. Since then, IGABT has been spreading, particularly in
      Europe, North America and Asia, and the guidelines have proved their broad
      acceptance and applicability in clinical practice. However, a unified approach to
      volume contouring and reporting does not imply a unified administration of
      treatment, and currently both external beam radiotherapy (EBRT) and IGABT are
      delivered using a large variety of techniques and prescription/fractionation
      schedules. With IGABT, local control is excellent in limited and well-responding
      tumours. The major challenges are currently loco-regional control in advanced
      tumours, treatment-related morbidity, and distant metastatic disease. Emerging
      evidence from the RetroEMBRACE and EMBRACE I studies has demonstrated that
      clinical outcome is related to dose prescription and technique. The next logical
      step is to demonstrate excellent clinical outcome with the most advanced EBRT and
      brachytherapy techniques based on an evidence-based prospective dose and volume
      prescription protocol. The EMBRACE II study is an interventional and
      observational multicentre study which aims to benchmark a high level of local,
      nodal and systemic control while limiting morbidity, using state of the art
      treatment including an advanced target volume selection and contouring protocol
      for EBRT and brachytherapy, a multi-parametric brachytherapy dose prescription
      protocol (clinical validation of dose constraints), and use of advanced EBRT
      (IMRT and IGRT) and brachytherapy (IC/IS) techniques (clinical validation). The
      study also incorporates translational research including imaging and tissue
      biomarkers.

PMID- 29594254
TI  - A Simple PCR-based Strategy for the Introduction of Point Mutations in the Yeast
      Saccharomyces cerevisiae via CRISPR/Cas9.
AB  - The methods currently employed for in vivo site-directed mutagenesis in yeast are
      laborious and/or inefficient. Recent developments of the CRISPR-based approaches
      hold great promise for genome editing, but its application in the yeast S.
      cerevisiae remains a time-consuming affair. The rate-limiting step in CRISPR
      mediated genetic engineering in yeast is the incorporation of the guide
      sequences, which target Cas9 to relevant chromosomal locus, into the relevant
      yeast vectors. Here we present a PCR-based strategy to introduce specific point
      mutation into the yeast CDC48 gene via CRISPR. Our method eliminates the need for
      special dam- strain and markedly shortens the elaborate multi-step cloning
      process, leading to significant savings in time, labor and cost.

PMID- 29594255
TI  - Enhanced Expression of the Key Mitosis Regulator Cyclin B1 Is Mediated by PDZ
      Binding Kinase in Islets of Pregnant Mice.
AB  - The proliferation of pancreatic beta cells is enhanced to enable an increase in
      beta-cell mass and to compensate for insulin resistance during pregnancy. To
      elucidate the mechanisms involved, we previously investigated islets from
      pregnant and nonpregnant mice by gene expression profiling and found that the
      expression of postsynaptic density-95/Discs large/zonula occludens-1 (PDZ)
      binding kinase (Pbk), a member of the mitogen-activated protein kinase kinase
      family, is increased in pregnant mouse islets compared with control mouse islets.
      Among the pregnancy hormones, treatment with estradiol upregulated Pbk
      expression. Inhibition of Pbk expression using a small interfering RNA for Pbk
      reduced bromodeoxyuridine incorporation in mouse insulinoma 6 cells, which was
      accompanied by a decreased expression of Ccnb1, a regulatory gene involved in
      mitosis. Ccnb1 expression was augmented in mouse islets during pregnancy. The
      forced expression of Pbk using an adenovirus system in isolated mouse islets
      increased Ccnb1 expression, and the Pbk inhibitor HI-TOPK-032 suppressed Ccnb1
      expression in islets isolated from pregnant mice. Our results suggest that Pbk
      contributes to the expansion of islets during pregnancy and that Ccnb1 may assist
      Pbk in its role in beta-cell proliferation.

PMID- 29594256
TI  - From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary
      Control of Thyroid Function.
AB  - Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein
      highly expressed in the mammalian pituitary gland. Shortly after its discovery in
      1998, the protein was proposed to function as a coreceptor for inhibins (and was
      even temporarily renamed inhibin binding protein). However, subsequent
      investigations, both in vitro and in vivo, failed to support a role for IGSF1 in
      inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next
      generation sequencing identified mutations in the X-linked IGSF1 gene in boys and
      men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope
      cells, implicating the protein in pituitary control of the thyroid.
      Investigations in two Igsf1 knockout mouse models converged to show that IGSF1
      deficiency leads to reduced expression of the receptor for thyrotropin-releasing
      hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a
      candidate mechanism for the central hypothyroidism observed in patients.
      Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain
      unresolved. Moreover, IGSF1 mutations are also commonly associated with other
      clinical phenotypes, including prolactin and growth hormone dysregulation, and
      macroorchidism. How the loss of IGSF1 produces these characteristics is unknown.
      Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with
      the results of detailed clinical investigations, powerful mouse models, and new
      reagents, the field is now poised to discover IGSF1's function in endocrine
      tissues, including the pituitary and testes.

PMID- 29594257
TI  - Plasma IL-1 Receptor Antagonist Concentration Has an Inverse Association With
      Birth Weight in Prepubertal Children.
AB  - Context: Birth size has an impact on later cardiometabolic risk that is strongly
      related to low-grade inflammation. Objective: To evaluate plasma interleukin-1
      receptor antagonist (IL-1ra) concentrations in relation to birth size and
      cardiometabolic and inflammatory markers in prepubertal children. Design: A
      cohort study. Anthropometric data were recorded. Fasting blood samples were
      collected for plasma analyses of IL-1ra, alanine transaminase, total cholesterol,
      high- and low-density lipoprotein cholesterols, triglyceride, glucose, and serum
      analyses of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein
      (hs-CRP) concentrations. Participants: Forty-nine large for gestational age
      (LGA), 56 appropriate for gestational age, and 23 small for gestational age (SGA)
      children at 5 to 8 years of age were examined. Main Outcome Measures: Differences
      in IL-1ra concentrations among the birth-size groups and associations between IL
      1ra and other metabolic markers were assessed. Results: Body mass index (BMI)
      standard deviation score (SDS)-adjusted plasma IL-1ra concentrations were highest
      in the SGA- and lowest in the LGA-born children (P = 0.015). Age- and sex
      adjusted IL-1ra concentrations had strongest associations with BMI SDS (P <
      0.001) and hs-CRP (P < 0.001, also when further adjusted for BMI SDS).
      Conclusions: Prepubertal children born SGA had the highest and those born LGA the
      lowest IL-1ra concentrations in this study cohort. Most associations found
      between IL-1ra and the studied metabolic parameters were weight related, but the
      association with hs-CRP remained strong after adjustment for BMI. It seems that
      at prepuberty, SGA children have a stronger inflammatory state than LGA children
      and may thus be at a greater risk for later metabolic disturbances.

PMID- 29594258
TI  - Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic
      Metabolism in Growth Hormone Deficiency.
AB  - Context: Growth hormone deficiency (GHD) leads to obesity and may induce tissue
      hypoxia. As (pro)renin receptor [(P)RR] is reported to contribute to the aerobic
      metabolism by stabilizing pyruvate dehydrogenase (PDH), it may play a substantial
      role in GHD. Objective: We aimed to investigate serum soluble (P)RR [s(P)RR]
      concentration, the origin of s(P)RR, and significance of (P)RR in GHD. Design
      Setting and Participants: Serum s(P)RR concentration was examined in 72 patients
      with pituitary diseases, including 32 patients with severe GHD (SGHD) and after
      GH replacement in 16 SGHD patients. Leptin-deficient ob/ob obese mice were
      treated with pegvisomant, a GH receptor antagonist, to explore the source of
      elevated serum s(P)RR in GHD. Adipocytes were cultured with 5% O2 to examine the
      effects of hypoxia. Results: Serum s(P)RR concentration was higher in patients
      with SGHD than in those without SGHD. Obesity was the important determinant of
      s(P)RR concentration. Serum s(P)RR concentration significantly decreased after GH
      replacement in SGHD patients. (P)RR mRNA expression was increased specifically in
      the adipose tissue (AT) of pegvisomant-treated obese mice compared with that of
      control obese mice. Hypoxia in cultured adipocytes increased (P)RR expression
      without affecting the PDH E1 beta subunit (PDHB) expression; however, with (P)RR
      knockdown by small interfering RNA, hypoxia significantly decreased the
      expression of PDHB. Conclusion: GHD patients showed increased serum s(P)RR
      concentration, possibly caused by obesity and hypoxia. (P)RR expression in AT of
      GHD patients may be elevated to help maintain aerobic metabolism under hypoxia.
      Thus, the elevated serum s(P)RR level may reflect hypoxia in ATs.

PMID- 29594259
TI  - 17beta-Estradiol and ICI182,780 Differentially Regulate STAT5 Isoforms in Female
      Mammary Epithelium, With Distinct Outcomes.
AB  - Prolactin (PRL) and estrogen cooperate in lobuloalveolar development of the
      mammary gland and jointly regulate gene expression in breast cancer cells in
      vitro. Canonical PRL signaling activates STAT5A/B, homologous proteins that have
      different target genes and functions. Although STAT5A/B are important for
      physiological mammary function and tumor pathophysiology, little is known about
      regulation of their expression, particularly of STAT5B, and the consequences for
      hormone action. In this study, we examined the effect of two estrogenic ligands,
      17beta-estradiol (E2) and the clinical antiestrogen, ICI182,780 (ICI,
      fulvestrant) on expression of STAT5 isoforms and resulting crosstalk with PRL in
      normal and tumor murine mammary epithelial cell lines. In all cell lines, E2 and
      ICI significantly increased protein and corresponding nascent and mature
      transcripts for STAT5A and STAT5B, respectively. Transcriptional regulation of
      STAT5A and STAT5B by E2 and ICI, respectively, is associated with recruitment of
      estrogen receptor alpha and increased H3K27Ac at a common intronic enhancer 10 kb
      downstream of the Stat5a transcription start site. Further, E2 and ICI induced
      different transcripts associated with differentiation and tumor behavior. In
      tumor cells, E2 also significantly increased proliferation, invasion, and stem
      cell-like activity, whereas ICI had no effect. To evaluate the role of STAT5B in
      these responses, we reduced STAT5B expression using short hairpin (sh) RNA.
      shSTAT5B blocked ICI-induced transcripts associated with metastasis and the
      epithelial mesenchymal transition in both cell types. shSTAT5B also blocked E2
      induced invasion of tumor epithelium without altering E2-induced transcripts.
      Together, these studies indicate that STAT5B mediates a subset of protumorigenic
      responses to both E2 and ICI, underscoring the need to understand regulation of
      its expression and suggesting exploration as a possible therapeutic target in
      breast cancer.

PMID- 29594260
TI  - Endocrine Disorders in Primary Mitochondrial Disease.
AB  - Context: Endocrine disorders are common in individuals with mitochondrial
      disease. To develop evidence-based screening practices in this high-risk
      population, updated age-stratified estimates of the prevalence of endocrine
      conditions are needed. Objective: To measure the point prevalence of selected
      endocrine disorders in individuals with mitochondrial disease. Design Setting and
      Patients: The North American Mitochondrial Disease Consortium Patient Registry is
      a large, prospective, physician-curated cohort study of individuals with
      mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of
      primary mitochondrial disease confirmed by molecular genetic testing. Main
      Outcome Measures: Age-specific prevalence of diabetes mellitus (DM), abnormal
      growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism.
      Results: The majority of our sample was pediatric (<18 years; 60.1%), female
      (56.9%), and white (85.9%). DM affected 2% of participants aged <18 years [95%
      confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI:
      18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial
      encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS;
      31.9%, of whom 86.2% had the m.3243A>G mutation). DM occurred more often with
      mitochondrial DNA defects (point mutations and/or deletions) than with nuclear
      DNA mutations (23.3% vs 3.7%, respectively; P < 0.001). Other prevalence
      estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%)
      for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism.
      Conclusion: DM and AGSM are highly prevalent in primary mitochondrial disease.
      Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre/Pearson syndrome
      spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical
      screening practices should reflect the substantial prevalence of endocrine
      disorders in mitochondrial disease.

PMID- 29594261
TI  - Early Detection of Rapid Cystic Fibrosis Disease Progression Tailored to Point of
      Care: A Proof-of-Principle Study.
AB  - Slowing cystic fibrosis (CF) lung disease progression is crucial to survival, but
      point-of-care technologies aimed at early detection-and possibly prevention-of
      rapid lung function decline are limited. This proof-of-principle study leverages
      a rich national patient registry and follow-up data on a local CF cohort to build
      an algorithm and prototype prognostic tool aimed at early detection of rapid lung
      function decline. The algorithm was developed using a novel longitudinal analysis
      of lung function (measured as forced expiratory volume in 1 s of % predicted,
      FEV1). Covariates included clinical and demographic characteristics selected from
      the registry based on information criterion. Preliminary assessment of algorithm
      performance suggested excellent predictive accuracy and earlier detection of
      rapid decline than standard of care being applied at a local center. Graphical
      displays were presented and evaluated for clinical utility. Predictions from the
      algorithms and chosen graphical displays were translated into a prototype web
      application using RShiny and underwent iterative development based on clinician
      feedback. This paper suggests that the algorithm and its translation could offer
      a means for earlier detection and treatment of rapid decline, providing
      clinicians with a viable point-of-care technology to intervene prior to
      irreversible lung damage.

PMID- 29594262
TI  - Multi-Atlas Based Segmentation of Brainstem Nuclei from MR Images by Deep Hyper
      Graph Learning.
AB  - Accurate segmentation of brainstem nuclei (red nucleus and substantia nigra) is
      very important in various neuroimaging applications such as deep brain
      stimulation and the investigation of imaging biomarkers for Parkinson's disease
      (PD). Due to iron deposition during aging, image contrast in the brainstem is
      very low in Magnetic Resonance (MR) images. Hence, the ambiguity of patch-wise
      similarity makes the recently successful multi-atlas patch-based label fusion
      methods have difficulty to perform as competitive as segmenting cortical and sub
      cortical regions from MR images. To address this challenge, we propose a novel
      multi-atlas brainstem nuclei segmentation method using deep hyper-graph learning.
      Specifically, we achieve this goal in three-fold. First, we employ hyper-graph to
      combine the advantage of maintaining spatial coherence from graph-based
      segmentation approaches and the benefit of harnessing population priors from
      multi-atlas based framework. Second, besides using low-level image appearance, we
      also extract high-level context features to measure the complex patch-wise
      relationship. Since the context features are calculated on a tentatively
      estimated label probability map, we eventually turn our hyper-graph learning
      based label propagation into a deep and self-refining model. Third, since
      anatomical labels on some voxels (usually located in uniform regions) can be
      identified much more reliably than other voxels (usually located at the boundary
      between two regions), we allow these reliable voxels to propagate their labels to
      the nearby difficult-to-label voxels. Such hierarchical strategy makes our
      proposed label fusion method deep and dynamic. We evaluate our proposed label
      fusion method in segmenting substantia nigra (SN) and red nucleus (RN) from 3.0 T
      MR images, where our proposed method achieves significant improvement over the
      state-of-the-art label fusion methods.

PMID- 29594263
TI  - Tandem trapped ion mobility spectrometry.
AB  - There is currently a strong interest in the use of ion mobility spectrometry-mass
      spectrometry (IMS-MS) instrumentation for structural biology. In these
      applications, momentum transfer cross sections derived from IMS-MS measurements
      are used to reconstruct the three-dimensional analyte structure. Recent reports
      indicate that additional structural information can be extracted from measuring
      changes in cross sections in response to changes of the analyte structure. To
      further this approach, we constructed a tandem trapped IMS analyser (TIMS-TIMS)
      and incorporated it in a QqTOF mass spectrometer. TIMS-TIMS is constructed by
      coupling two TIMS analysers via an "interface region" composed of two apertures.
      We show that peptide oligomers (bradykinin) and native-like protein (ubiquitin)
      ions can be preserved through the course of an experiment in a TIMS-TIMS
      analyser. We demonstrate the ability to collisionally-activate as well as to trap
      mobility-selected ions, followed by subsequent mobility-analysis. In addition to
      inducing conformational changes, we show that we can fragment low charge states
      of ubiquitin at >1 mbar between the TIMS analysers with significant sequence
      coverage. Many fragment ions exhibit multiple features in their TIMS spectra,
      which means that they may not generally exist as the most stable isomer. The
      ability of TIMS-TIMS to dissociate mobility-selected protein ions and to measure
      the cross sections of their fragment ions opens new possibilities for IMS-based
      structure elucidation.

PMID- 29594264
TI  - Multicolor GLUT5-permeable fluorescent probes for fructose transport analysis.
AB  - The specificity of carbohydrate transporters towards their substrates poses a
      significant challenge for the development of molecular probes to monitor sugar
      uptake in cells for biochemical and biomedical applications. Herein we report a
      new set of coumarin-based fluorescent sugar conjugates applicable for the
      analysis of fructose uptake due to their free passage through the fructose
      specific transporter GLUT5. The reported probes cover a broad range of the
      fluorescence spectrum providing essential tools for the evaluation of fructose
      transport capacity in live cells.

PMID- 29594269
TI  - Nano X-ray diffractometry device for nanofluidics.
AB  - Nanofluidics is gaining attention because it has unique liquid and fluidic
      properties that are not observed in microfluidics. It has been reported that many
      liquid properties change when the size of a fluidic channel is reduced below 500
      800 nm. To discuss the underlying mechanism, information on the microscopic
      liquid structure must be obtained (e.g., by X-ray diffractometry). However, the
      very small volume (attoliters to femtoliters) of a nanochannel and the large
      volume of its glass substrate prevent measurement of signals from the nanochannel
      liquid. In this study, we report a novel nanofluidic device that can be used in
      conjunction with X-ray diffractometry to analyze the structure of water confined
      in nanochannels. Top-down and bottom-up micro- and nano-fabrication processes
      were established, and the substrate thickness of the measurement area was reduced
      to only 2.7 MUm, which was almost 1000 times smaller than that of conventional
      substrates (millimeter scale). With this new device, X-ray diffraction signals
      were clearly observed in nanochannels 500 nm wide and deep. Based on the X-ray
      diffraction pattern, the radial distribution function was calculated, which
      showed a structure nearly similar to that of a bulk sample. Therefore, X-ray
      diffractometry in nanochannels was realized. This method will provide important
      information on how a liquid behaves when confined in a nanospace and contribute
      to chemistry and biology on scales of 10-100 nm (e.g., inter- and intra-cellular
      spaces). It is also important for designing chemical reactions and fluidic
      circuits in nanochannels for realizing highly functional devices.

PMID- 29594270
TI  - Synthesis of ultrathin Ni nanosheets for semihydrogenation of phenylacetylene to
      styrene under mild conditions.
AB  - The synthesis of ultrathin metal nanosheets (NSs) attracts broad scientific and
      technological interest, and it still remains a challenge for non-noble metals
      like nickel due to their intrinsic cubic symmetry and high surface energy.
      Herein, we report a NiO intermediated solvothermal method towards the synthesis
      of ultrathin Ni NSs (thickness < 3 nm) using N,N-dimethylformamide as the solvent
      and n-butylamine as the shape controlling reagent. The growth of the ultrathin Ni
      NSs follows an intermediate mechanism which was proved by the results obtained by
      means of transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray
      absorption spectra (XAS) and X-ray photoelectron spectroscopy (XPS). Under
      solvothermal conditions, the nickel acetylacetonate precursor was first reduced
      to a NiO NS intermediate, then reduction occurred and NiO NSs were reduced to Ni
      NSs. The synthesized ultrathin Ni NSs predominately in a metallic state showed
      high selectivity (88.0-92.0%) towards styrene (ST) in the phenylacetylene (PA)
      semihydrogenation reaction under mild conditions (323 K, 1 atm of hydrogen) in a
      broad PA conversion range (2.0-98.0%). The low coverage of oxygen atoms on the Ni
      NS surface is proposed to account for the high ST selectivity, as indicated by
      density functional theory (DFT) calculations.

PMID- 29594271
TI  - Shaping metal-organic framework materials with a honeycomb internal structure.
AB  - A self-assembly technology allows metal-organic framework materials to constitute
      a honeycomb internal structure while being shaped into millimeter-scale spheres.
      The ZIF-8 load is up to 83 wt% through solidification of chitosan (CS). This
      approach can be expanded to other morphologies (fibers) or crystals and is
      transformative for industrial manufacturing of nanomaterials.

PMID- 29594272
TI  - Terpyridine-based metallosupramolecular constructs: tailored monomers to precise
      2D-motifs and 3D-metallocages.
AB  - This overview represents a comprehensive summary of the recent developments in
      the growing field of terpyridine-based, discrete metallosupramolecular
      architectures. The N-heteroaromatic ligand [2,2':6',2'']terpyridine (tpy)
      presents a convergent N,N',N''-chelating donor set and has the ability to bind
      diverse metal ions to form stable pseudo-octahedral tpy-M2+-tpy bonds. Use of tpy
      M2+-tpy connectivity for the edges and directed organic vertices has opened the
      door to diverse, dynamic, utilitarian macromolecular materials. New strategies
      have been employed to synthesize a range of 2D- and 3D-fractals as well as novel
      macrocyclic constructs by employing new designer strategies, such as: triangle
      based frameworks, hexagonal fractal designs, flexible polyterpyridine linkers,
      and noncovalent interactions for spontaneous quantitative self-assembly. Numerous
      examples of heteroleptic self-assembly have been described along with the
      synthesis of heterometallic conjugates using step-wise protocols. Utilizing
      multiplanar, directed spacer units in the polyterpyridine vertices, new 3D
      polyhedra were obtained facilitating the assembly of hybrid fractal-dendritic
      materials. These constructs are shown to undergo tunable conformational
      transformations by responding to specific stimuli such as concentration,
      temperature, and counter ions. The increasing ability to exploit hierarchical
      self-assembly of complex, higher order supramolecular nanomaterials is discussed.

PMID- 29594273
TI  - The impact of galactooligosaccharides on the bioaccessibility of sterols in a
      plant sterol-enriched beverage: adaptation of the harmonized INFOGEST digestion
      method.
AB  - The effect of the addition of galactooligosaccharides (GOS) on sterol
      bioaccessibility in three plant sterol (PS)-enriched milk-based fruit beverages
      (without GOS addition (MfB) and with 2.5 g (MfB-G2) and 5.0 g (MfB-G5) GOS per
      250 mL) was evaluated after micellar gastrointestinal digestion. Cholesterol
      bioaccessibility was very similar among beverages, though a slight significant
      increase (from 80% to 85%) was observed by the addition of 5.0 g GOS. The
      addition of GOS did not affect total PS bioaccessibility (~37%). Based on the
      results obtained after micellar digestion, it has been demonstrated that these
      beverages could be a suitable food matrix for simultaneous enrichment with PS and
      GOS. The harmonized in vitro digestion model INFOGEST was applied to the MfB
      beverage, but the cholesterol content could not be quantified due to its
      contribution of bile salts. Hence, it was proposed: (i) a change in porcine bile
      salt concentration from 10 mM to 1.4 mM (in order to compare with micellar
      digestion); or (ii) a change of bile salt origin (bovine instead of porcine),
      maintaining physiological concentration (10 mM, INFOGEST condition). Both options
      allowed cholesterol quantification, with bioaccessibilities of 62% (reduction of
      bile salts) and 38% (replacement of the bile salt source), whereas plant sterol
      bioaccessibilities were 22% and 14%, respectively. Therefore, the change of bile
      salt origin maintaining INFOGEST concentration is proposed as a method to
      evaluate sterol (cholesterol and PS) bioaccessibility in these beverages,
      demonstrating the need for the selection of appropriate conditions of the
      INFOGEST harmonized method according to the food matrix and compounds to be
      determined.

PMID- 29594275
TI  - Oligothienyl catenated germanes and silanes: synthesis, structure, and
      properties.
AB  - The synthesis of two new groups of oligothienyl catenated silanes and germanes,
      Me5M2Thn (1a-b), Me5M2ThnM2Me5 (2a-c) (terminal), and ThnM2Me4Thn (3a-d)
      (internal) (M = Si, Ge; n = 2, 3; Th = 2- or 2,5-thienyl), is reported. The study
      of their structural parameters as well as of their spectral (NMR),
      electrochemical (CV) and optical (UV/vis absorbance, luminescence) properties has
      been performed in detail; in addition, the unexpected compound [Th2Si2Me4Th]2
      (3a') is also studied. Theoretical investigations have been performed for model
      compounds in order to establish structure-property relationships. The molecular
      structures of 2a (Me5Si2Th2Si2Me5), 2b (Me5Ge2Th2Ge2Me5), 3a (Th2Si2Me4Th2) and
      3b (Th2Ge2Me4Th2) have been investigated by X-ray diffraction analysis. An
      effective conjugation with flattening of both Th planes in terminal 2a and 2b was
      observed. The main trends in the dependence of the optical and electrochemical
      properties on the structural parameters have been established. All of the
      compounds studied exhibit a strong emission within the 378-563 nm range, and the
      maximal quantum yield (up to 77%) is observed for the Si derivative 3a'. For the
      majority of the compounds, the quantum yields (20-30%) are significantly larger
      than for 2,2'-bi- and 2,2':5',5''-terthiophenes. Due to their good emission
      properties, these compounds could be used to develop new materials with specific
      spectral properties.

PMID- 29594274
TI  - Luminescence mechanisms of ultrasmall gold nanoparticles.
AB  - The past decade has witnessed a burst of study on ultrasmall gold nanoparticles.
      Unlike semiconductor quantum dots, ultrasmall gold nanoparticles have very
      diverse emission mechanisms, which are often involved in many structural factors
      such as size, valence state, surface ligands and crystallinity. In this frontier,
      we summarize our latest advancement in the fundamental understanding of emission
      mechanisms of ultrasmall gold nanoparticles, which are expected to help us more
      precisely control their emissions and broaden their applications from energy
      technologies to disease detection.

PMID- 29594276
TI  - Defect engineering in 1D Ti-W oxide nanotube arrays and their correlated
      photoelectrochemical performance.
AB  - Understanding the nature of interfacial defects of materials is a critical
      undertaking for the design of high-performance hybrid electrodes for
      photocatalysis applications. Theoretical and computational endeavors to achieve
      this have touched boundaries far ahead of their experimental counterparts.
      However, to achieve any industrial benefit out of such studies, experimental
      validation needs to be systematically undertaken. In this sense, we present
      herein experimental insights into the synergistic relationship between the
      lattice position and oxidation state of tungsten ions inside a TiO2 lattice, and
      the respective nature of the created defect states. Consequently, a roadmap to
      tune the defect states in anodically-fabricated, ultrathin-walled W-doped TiO2
      nanotubes is proposed. Annealing the nanotubes in different gas streams enabled
      the engineering of defects in such structures, as confirmed by XRD and XPS
      measurements. While annealing under hydrogen stream resulted in the formation of
      abundant Wn+ (n < 6) ions at the interstitial sites of the TiO2 lattice, oxygen-
      and air-annealing induced W6+ ions at substitutional sites. EIS and Mott-Schottky
      analyses indicated the formation of deep-natured trap states in the hydrogen
      annealed samples, and predominantly shallow donating defect states in the oxygen-
      and air-annealed samples. Consequently, the photocatalytic performance of the
      latter was significantly higher than those of the hydrogen-annealed counterparts.
      Upon increasing the W content, photoelectrochemical performance deteriorated due
      to the formation of WO3 crystallites that hindered charge transfer through the
      photoanode, as evident from the structural and chemical characterization. To this
      end, this study validates the previous theoretical predictions on the detrimental
      effect of interstitial W ions. In addition, it sheds light on the importance of
      defect states and their nature for tuning the photoelectrochemical performance of
      the investigated materials.

PMID- 29594278
TI  - Room-temperature distance measurements using RIDME and the orthogonal spin labels
      trityl/nitroxide.
AB  - Electron paramagnetic resonance (EPR) based nanometer distance measurements at
      ambient temperatures are of particular interest for structural biology
      applications. The nitroxide spin labels commonly used in EPR reveal relatively
      short transverse relaxation under these conditions, which limits their use for
      detecting static dipolar interactions. At the same time, the longitudinal
      relaxation of nitroxide spin labels is still long enough to allow using them as
      'pumped' species in the relaxation induced dipolar modulation enhancement (RIDME)
      experiment where the detection is carried out on the slower relaxing
      triarylmethyl (TAM) spin labels. In the present study, we report the first
      demonstration of room-temperature RIDME distance measurements in nucleic acids
      using TAM as the slow-relaxing detected species and traditional nitroxide as the
      fast-relaxing partner spin. Two types of immobilizers, glassy trehalose and the
      modified silica gel Nucleosil, were used for immobilization of the spin-labeled
      biomolecules. The room-temperature RIDME-based distance distributions are in good
      agreement with those measured at 80 K by other techniques. Room-temperature RIDME
      on the spin pairs trityl/nitroxide may become a useful method for the structural
      characterization of biomacromolecules and biomolecular complexes at near
      physiological temperatures.

PMID- 29594279
TI  - Enhancement of SOD activity in boehmite supported nanoreceptors.
AB  - The binuclear Cu2+ complex of a pyridinophane polyamine ligand ranking amongst
      the fastest SOD mimetics so far reported displays a remarkable SOD activity
      enhancement when grafted to the surface of boehmite (gamma-AlO(OH)) nanoparticles
      (BNPs).

PMID- 29594280
TI  - Theoretical study on the origin of activity for the oxygen reduction reaction of
      metal-doped two-dimensional boron nitride materials.
AB  - Two-dimensional boron nitride (2D-BN) materials doped with metallic atoms are
      suitable candidates for the oxygen reduction reaction (ORR) to replace Pt-based
      catalysts. In this study, a series of model 2D-BN materials doped with metallic
      atoms were designed to uncover the relationship between ORR activity and metallic
      dopants. A volcano curve correlation was derived between ORR overpotential and
      the adsorption free energy values of *OH. Only the doped structures, located at
      the top of the volcano curve, exhibit optimized activity. Through analyzing the
      dynamic results, the ORR was found to occur only via the 4e- pathway on Co doped
      2D-BN materials with the activation energy of 0.30 eV, which is lower than that
      achieved with the state-of-the-art Pt-based catalysts (0.79 eV). Furthermore,
      based on the calculations of electronic structure properties, we find that the
      small highest occupied molecular orbital (HOMO)-lowest unoccupied molecular
      orbital (LUMO) gap is more beneficial to the 4e- pathway and prove that the
      binding strength between metallic atoms-doped 2D-BN materials and oxygenated
      intermediates is regulated by the HOMO of the metallic dopant consisting non
      bonding or delocalized orbitals. These results provide an effective method to
      facilitate the design of new BN-based materials with high electrocatalytic
      performances besides the ORR performance.

PMID- 29594277
TI  - Catalytic peptide assemblies.
AB  - Self-assembly of molecules often results in new emerging properties. Even very
      short peptides can self-assemble into structures with a variety of physical and
      structural characteristics. Remarkably, many peptide assemblies show high
      catalytic activity in model reactions reaching efficiencies comparable to those
      found in natural enzymes by weight. In this review, we discuss different
      strategies used to rationally develop self-assembled peptide catalysts with
      natural and unnatural backbones as well as with metal-containing cofactors.

PMID- 29594281
TI  - In vivo drug tracking with 19F MRI at therapeutic dose.
AB  - Tracking drugs with 19F MRI would be beneficial for developing theranostics and
      optimizing drug therapy. To this end, a fluorinated dendritic amphiphile with
      high 19F MRI sensitivity and biocompatibility has been developed for 19F MRI
      tracking of doxorubicin (DOX)-loaded liposomes in mice, which may provide an
      effective platform to in vivo trace various drugs with 19F MRI.

PMID- 29594282
TI  - On the hydrogen evolution reaction activity of graphene-hBN van der Waals
      heterostructures.
AB  - Although graphene technology has reached technology readiness level 9 and
      hydrogen fuel has been identified as a viable futuristic energy resource,
      pristine atomic layers such as graphene are found to be inactive towards the
      hydrogen evolution reaction (HER). Enhancing the intrinsic catalytic activity of
      a material and increasing its number of active sites by nanostructuring are two
      strategies in novel catalyst development. Here, electrocatalytically inert
      graphene (G) and hexagonal boron nitride (hBN) are made active for the HER by
      forming van der Waals (vdW) heterostructures via vertical stacking. The HER
      studies are conducted using defect free shear exfoliated graphite and hBN
      modified glassy carbon electrodes via layer by layer sequential stacking. The
      G/hBN stacking pattern (AA, AB, and AB') and stacking sequence (G/hBN or hBN/G)
      have been found to play important roles in the HER activity. Enhancement in the
      intrinsic activity of graphene by the formation of G/hBN vdW stacks has been
      further confirmed with thermally reduced graphene oxide and hBN based structures.
      Tunability in the HER performance of the G/hBN vdW stack is also confirmed via a
      three-dimensional rGO/hBN electrode. HER active sites in the G/hBN vdW structures
      are then mapped using density functional theory calculations, and an atomistic
      interpretation has been identified.

PMID- 29594283
TI  - Rheology of phosphonium ionic liquids: a molecular dynamics and experimental
      study.
AB  - We have studied the rheological behavior of the ionic liquid
      trihexyl(tetradecyl)phosphonium bis(mandelato)borate, [P66614][BMB], and compared
      it with that of another ionic liquid, namely trihexyl(tetradecyl)phosphonium
      chloride, [P66614][Cl]. The non-halogenated [P66614][BMB] has been selected as it
      is known to provide enhanced lubrication performance and is, consequently, of
      technological importance. The ionic liquid [P66614][Cl], despite its relatively
      simple anion, exhibits viscosities very similar to those of [P66614][BMB], making
      it an excellent reference fluid for the modeling study. The viscosities of the
      ionic liquids have been obtained by equilibrium atomistic simulations using the
      Green-Kubo relation, and by performing nonequilibrium shear flow simulations. The
      influence of the simulation system size and a reduction of the atomic charges on
      the viscosities of the ionic liquids are systematically studied. The atomic
      charges are reduced to mimic the temperature dependent charge transfer and
      polarization effects. It has been found that scaling the point charges with
      factors between 0.60 and 0.80 from full ion charges can provide reliable
      viscosities of [P66614][BMB], consistent with the experimentally measured
      viscosities within the studied temperature interval from 373 to 463 K. The
      viscosities of [P66614][Cl] have been obtained with scaling factors between 0.80
      and 1.0 reflecting the lower polarizability and charge transfer effects of the
      chloride anion.

PMID- 29594284
TI  - High-performing ultrafast transparent photodetector governed by the pyro
      phototronic effect.
AB  - In this work we utilized the advantage of the photo-induced pyroelectric effect -
      known as "Pyro-phototronic" - to design a self-powered, ultrafast, transparent
      ultraviolet (UV, 365 nm) photodetector. The device architecture contains an UV
      absorbing pyroelectric ZnO layer sandwiched between hole-selective V2O5 and a
      bottom ITO electrode. In addition, the device shows a high optical transmittance,
      >70%, in the entire visible region. The photo current of the device was enhanced
      from 19 to 42 MUA under pulsed UV light illumination (lambda = 365 nm, 4 mW cm-2)
      by exploiting the pyro-phototronic potential. In addition, the photodetector
      demonstrated ultrafast responses of ~4 MUs for the rise time and ~16 MUs for the
      fall time. Further, a high photoresponsivity of ~36.34 mA W-1 and excellent
      photodetectivity of ~6.04 * 1014 Jones, with an enhancement of 725% in both due
      to the pyroelectric potential, were measured. This novel approach will open a new
      path to design transparent and ultrafast devices, as well as on the flexible
      substrates, for future optoelectronic applications.

PMID- 29594285
TI  - Paeoniflorin prevents endoplasmic reticulum stress-associated inflammation in
      lipopolysaccharide-stimulated human umbilical vein endothelial cells via the
      IRE1alpha/NF-kappaB signaling pathway.
AB  - Endoplasmic reticulum (ER) stress-associated inflammation is a critical molecular
      mechanism involved in the pathogenesis of endothelial dysfunction (ED). Hence,
      strategies for alleviating ER stress-induced inflammation may be essential for
      the prevention of cardiovascular diseases. Paeoniflorin (PF), a bioactive
      compound from Paeonia lactiflora Pallas is known for its functional properties
      against vascular inflammation. However, to date, PF-mediated protection against
      ER stress-dependent inflammation has not been identified. Herein, we investigate
      the protective effect of PF on lipopolysaccharide (LPS)-stimulated human
      umbilical vein endothelial cell (HUVEC) injury and explore its underlying
      mechanism. The result of the cell viability assay indicates that PF promotes the
      cell survival rate in LPS-stimulated HUVECs. In addition, the LPS-induced over
      production of inflammatory cytokines (interleukin-6 (IL-6) and monocyte
      chemotactic protein 1 (MCP-1)) and ER stress markers (78 kDa glucose regulated
      protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)) are
      significantly decreased by PF and the ER stress inhibitor 4-phenylbutric acid (4
      PBA). The transmission electron microscopy (TEM) assay implies that the
      ultrastructural abnormalities in ER are reversed by PF treatment, which is
      similar to the protective effect of 4-PBA. Impressively, we find that the
      inositol-requiring enzyme 1alpha (IRE1alpha)/nuclear factor-kappa B (NF-kappaB)
      pathway is significantly activated and contributes to the progress of LPS-induced
      HUVEC injury by promoting inflammatory cytokine production. IRE1alpha siRNA,
      AEBSF (ATF6 inhibitor), GSK2656157 (PERK inhibitor), PDTC (NF-kappaB inhibitor)
      and thapsigargin (TG, IRE1 activator) are used to confirm the role of the
      IRE1alpha/NF-kappaB pathway in PF-mediated protection against LPS-induced HUVEC
      injury. Our findings indicate that PF has an inhibitory effect on endothelial
      injury. To summarize, PF might be a potential therapeutic agent to inhibit ER
      stress-associated vascular inflammation.

PMID- 29594286
TI  - Phonon mode transformation in size-evolved solution-processed inorganic lead
      halide perovskite.
AB  - Recently, lead halide perovskites have attracted significant scientific attention
      in the fields of photovoltaics, light emitting diodes, lasers, photo-detectors
      and other optoelectronic functional devices. The most stable crystal form of lead
      halide perovskites is the cube, including nano-cube and micro-cube, which hold
      great promise as functional materials due to their combination of unique
      optoelectronic properties and versatility through colloidal synthesis. Herein, we
      report the solution-processed synthesis of pure inorganic lead halide nano-cubes-
      and micro-cubes-based colloidal perovskites. The different size of cubes either
      into nano-cube or micro-cube are demonstrated that their phonon mode
      transformation which means the perovskite crystal structure phase change cross
      the nano-cube to micro-cube. The solution-processed colloidal synthesis method
      and phonon-mode transformation from nano-cube to micro-cube make pure inorganic
      lead halide perovskite an ideal platform for fundamental optoelectronic studies
      and the investigation of functional devices.

PMID- 29594287
TI  - Citrus medica: nutritional, phytochemical composition and health benefits - a
      review.
AB  - Citrus medica (Citron) is an underutilized fruit plant having various bioactive
      components in all parts of the plant. The major bioactive compounds present are
      iso-limonene, citral, limonene, phenolics, flavonones, vitamin C, pectin,
      linalool, decanal, and nonanal, accounting for several health benefits. Pectin
      and heteropolysachharides also play a major role as dietary fibers. The potential
      impact of citron and its bioactive components to prevent or reverse destructive
      deregulated processes responsible for certain diseases has attracted different
      researchers' attention. The fruit has numerous nutraceutical benefits, proven by
      pharmacological studies; for example, anti-catarrhal, capillary protector, anti
      hypertensive, diuretic, antibacterial, antifungal, anthelmintic, antimicrobial,
      analgesic, strong antioxidant, anticancerous, antidiabetic, estrogenic,
      antiulcer, cardioprotective, and antihyperglycemic. The present review explores
      new insights into the benefits of citron in various body parts. Throughout the
      world, citron has been used in making carbonated drinks, alcoholic beverages,
      syrup, candied peels, jams, marmalade, cordials, and many other value added
      products, which suggests it is an appropriate raw material to develop healthy
      processed food. In the present review, the fruit taxonomical classification,
      beneficial phytochemicals, antioxidant activities, and health benefits are
      discussed.

PMID- 29594288
TI  - Regulation of multi-factors (tail/loop/link/ions) for G-quadruplex
      enantioselectivity of Delta- and Lambda- [Ru(bpy)2(dppz-idzo)]2.
AB  - Chiral recognition of DNA molecules is important because much evidence has
      indicated that transformations of chirality and diverse conformations of DNA are
      involved in a series of key biological events. Among these, enrichment of G
      quadruplexes (GQs) in the genome, and the exploration of their multiple
      structures, has aroused great interest. Herein, we compared nearly 100 different
      sequences with 3'-tail sequences of variable length or different linkers or
      diverse loops and mutative ionic concentrations. All sequences were capable of
      forming stable GQs, with fluorescence signal enhancement upon binding with Delta-
      and Lambda- [Ru(bpy)2(dppz-idzo)]2+ (Delta/Lambda-1). Our results show that
      multiple factors, including the 3'-tail length, linkers, loop length and ionic
      concentration, regulate the enantioselectivity of GQs. Furthermore, molecular
      docking simulations revealed that chiral recognition of GQs depends on the
      binding site. To the best of our knowledge, this is the first systematic study
      regarding the regulation of multi-factors for GQ selectivity of chiral Ru
      complexes. These results will serve as a useful reference for enantioselective
      recognition of genomic GQs and may facilitate the development of chiral
      anticancer agents for targeting GQs.

PMID- 29594289
TI  - Selective growth of chirality-enriched semiconducting carbon nanotubes by using
      bimetallic catalysts from salt precursors.
AB  - Bimetallic catalysts play important roles in the selective growth of single
      walled carbon nanotubes (SWNTs). Using the simple salts (NH4)6W7O24.6H2O and
      Co(CH3COO)2.4H2O as precursors, tungsten-cobalt catalysts were prepared. The
      catalysts were composed of W6Co7 intermetallic compounds and tungsten-dispersed
      cobalt. With the increase of the W/Co ratio in the precursors, the content of
      W6Co7 was increased. Because the W6Co7 intermetallic compound can enable the
      chirality specified growth of SWNTs, the selectivity of the resulting SWNTs is
      improved at a higher W/Co ratio. At a W/Co ratio of 6 : 4 and under optimized
      chemical vapor deposition conditions, we realized the direct growth of
      semiconducting SWNTs with the purity of ~96%, in which ~62% are (14, 4) tubes.
      Using salts as precursors to prepare tungsten-cobalt bimetallic catalysts is
      flexible and convenient. This offers an efficient pathway for the large-scale
      preparation of chirality enriched semiconducting SWNTs.

PMID- 29594290
TI  - An aryl-fused redox-active tetrathiafulvalene with enhanced mixed-valence and
      radical-cation dimer stabilities.
AB  - Molecular recognition of stable organic radicals is a relatively novel, but
      important structural binding motif in supramolecular chemistry. Here, we report
      on a redox-switchable veratrole-fused tetrathiafulvalene derivative VTTF which is
      ideally suited for this purpose and for the incorporation into stimuli-responsive
      systems. As revealed by electrochemistry, UV/Vis measurements, X-ray analysis,
      and electrocrystallisation, VTTF can be reversibly oxidised to the corresponding
      radical-cation or dication which shows optoelectronic and structural propterties
      similar to tetrathiafulvalene and tetrakis(methylthio)tetrathiafulvalene.
      However, theoretical calculations, variable temperature EPR, and NIR spectroscopy
      indicate that the dispersion-driven binding in the mixed-valence dimer (VTTF2)+
      (KMV = 69 M-1 in CH2Cl2) and the radical-cation dimer (VTTF+)2 (KRC = 38 M-1 in
      CH3CN) is significantly enhanced by the additional veratrole pi-surface in
      comparison to pristine tetrathiafulvalene.

PMID- 29594292
TI  - Formation of highly luminescent cesium bismuth halide perovskite quantum dots
      tuned by anion exchange.
AB  - Cs3Bi2Br9 quantum dots (QDs) with photoluminescence quantum yields (PLQYs) of up
      to 22% were prepared through the steady binding of octylammonium bromide and
      oleic acid. Excellent thermal stability and good luminescence properties have
      been achieved as intrinsic features of the inorganic halide perovskites, as well
      as the effective passivation of surface trap-states.

PMID- 29594291
TI  - A supramolecular self-assembly strategy for upconversion nanoparticle
      bioconjugation.
AB  - An efficient surface modification for upconversion nanoparticles (UCNPs) is
      reported via supramolecular host-guest self-assembly. Cucurbit[7]uril (CB) can
      provide a hydrophilic surface and cavities for most biomolecules. High biological
      efficiency, activity and versatility of the approach enable UCNPs to be
      significantly applied in bio-imaging, early disease detection, and bio-sensing.

PMID- 29594293
TI  - Unconventional morphologies of CoO nanocrystals via controlled oxidation of
      cobalt oleate precursors.
AB  - We report an 'oxidation state' regulating method for the synthesis of anisotropic
      wurtzite CoO nanocrytals (NCs) with various shapes, including ultrathin
      nanosheets and a core-antenna structure for the first time. We show that the
      decomposition process of precursors was altered by their oxidation, which played
      a significant role in the unconventional growth.

PMID- 29594294
TI  - A first principle comparative study of the ionic diffusivity in LiAlO2 and NaAlO2
      polymorphs for solid-state battery applications.
AB  - Lithium aluminates are attracting increasing attention as battery materials. They
      are typically used for the coating of electrodes. The diffusive properties of the
      equilibrium tetragonal phase (gamma) are well understood from both an
      experimental and a theoretical perspective, and the major diffusive mechanism is
      recognised to be vacancy hopping between neighbouring sites. Investigations of
      this type are however not reported for other, high-pressure LiAlO2 phases.
      Moreover, the ionic diffusivity of the Na-based aluminates, manifesting a similar
      polymorphism to LiAlO2, has never been studied using atomistic techniques. In
      this work, we address these points, by presenting a comparative density
      functional theory-based study of these materials, describing the structural
      properties of the various phases, and evaluating the activation energies for
      single vacancy hops. While LiAlO2 exhibits a poor ionic conductivity due to a
      significant degree of covalency of the Al-O bonding, orthorhombic beta-NaAlO2
      exhibits a significantly lower diffusion barrier. This feature cannot be
      explained only in terms of the larger equilibrium volume, as the same trend is
      not observed for the high-pressure trigonal alpha-LiAlO2 and alpha-NaAlO2. We
      utilise here various electronic-structure tools to verify the lower degree of
      covalency of the Na-O bonds. The electron localisation function, in particular,
      is shown to be intrinsically correlated to the diffusion pathways of Li and Na
      ions, and its variation along the path is a qualitative measure of ionic
      conductivity.

PMID- 29594295
TI  - Structural and dielectric properties of cobaltacarborane composite
      polybenzimidazole membranes as solid polymer electrolytes at high temperature.
AB  - The conductivity of a series of composite membranes, based on polybenzimidazole
      (PBI) containing the metallacarborane salt M[Co(C2B9H11)2], M[COSANE] and
      tetraphenylborate, M[B(C6H5)4], M[TPB] both anions having the same number of
      atoms and the same negative charge, has been investigated. Different cations (M =
      H+, Li+ and Na+) have been studied and the composite membranes have been
      characterized by water uptake, swelling ratios, ATR FT-IR, thermogravimetric
      analysis and electrochemical impedance spectroscopy to explore the dielectric
      response and ion dynamics in composite membranes. Our results show that
      conductivity increases with increasing temperature and it is higher for H+ than
      for Li+ and Na+ for all temperatures under study. The mobility of Li+ is greater
      in [COSANE]- than in [TPB]- composite PBI@membranes while for Na+ it is the
      opposite. The temperature dependence of the conductivity of the composite was
      followed by a typical Arrhenius behaviour with two different regions: (1) between
      20 and 100  degrees C, and (2) between 100 and 150  degrees C. Using the analysis
      of electrode polarization (EP) based on the Thrukhan theory we have calculated
      the ionic diffusion coefficients and the density of carriers. From the double
      logarithmic plot of the imaginary part of the conductivity (sigma'') versus
      frequency in the entire range of temperatures studied we have determined for each
      sample at each temperature, the frequency values of the onset (fON) and full
      development of electrode polarization (fMAX), respectively, which permit us to
      calculate static permittivity.

PMID- 29594296
TI  - Ene cyclization reaction in heterocycle synthesis.
AB  - The ene cyclization has evolved to become an indispensable tool for the synthesis
      of various ring size heterocyclic compounds. In the past and recent years, many
      exciting reports have demonstrated the broad scope and synthetic utility of ene
      cyclization and the versatility of oxonium ion, iminium ion and thionium ion
      intermediates. Moreover, the ease of regio- and stereoselectivity of ene
      cyclization has led to the development of new types of heterocyclic compounds.
      This article aims at reviewing the utilities of ene cyclization reactions for the
      synthesis of various ring sizes of oxygen, nitrogen and sulfur heterocycles. It
      also covers some applications in natural product synthesis. The mechanism of the
      reactions is discussed wherever necessary. The review article covers the time
      period from 1986 to 2017.

PMID- 29594297
TI  - Exposed metal oxide active sites on mesoporous titania channels: a promising
      design for low-temperature selective catalytic reduction of NO with NH3.
AB  - A subtle catalyst design is provided with stably incorporated binary
      catalytically active centers of CuO and MnO2 on the surface wall of mesoporous
      TiO2. Such unique features render these mesoporous composites highly promising in
      the low-temperature selective catalytic reduction of NO with NH3, including high
      NO conversion efficiency, and superior H2O and SO2 resistance.

PMID- 29594298
TI  - One-step synthesis of cobalt-doped MoS2 nanosheets as bifunctional
      electrocatalysts for overall water splitting under both acidic and alkaline
      conditions.
AB  - Cobalt-doped MoS2 nanosheets were prepared via a facile hydrothermal method,
      exhibiting bifunctional activities of hydrogen and oxygen evolution reactions in
      both acidic and alkaline media. Cobalt doping not only improves the conductivity,
      decreasing the hydrogen adsorption free energy of MoS2 for HER, but also
      contributes catalytic active sites for OER.

PMID- 29594299
TI  - A chiral organic base catalyst with halogen-bonding-donor functionality:
      asymmetric Mannich reactions of malononitrile with N-Boc aldimines and ketimines.
AB  - A chiral organic base catalyst with halogen-bonding-donor functionality has been
      developed. This quinidine-derived acid/base catalyst smoothly promoted the
      asymmetric Mannich reaction of malononitrile and various N-Boc imines with up to
      98% ee. The cooperative interaction with both substrates was responsible for the
      high activity that allowed a reduction of the catalyst amount to 0.5 mol%.

PMID- 29594300
TI  - Theory of diffusioosmosis in a charged nanochannel.
AB  - We probe the diffusioosmotic transport in a charged nanofluidic channel in the
      presence of an applied tangential salt concentration gradient. Ionic salt
      gradient driven diffusioosmosis or ionic diffusioosmosis (IDO) is characterized
      by the generation of an induced tangential electric field and a diffusioosmotic
      velocity (DOSV) that is a combination of an electroosmotic velocity (EOSV)
      triggered by this electric field and a chemiosmotic velocity (COSV) triggered by
      an induced tangential pressure gradient. We explain that unlike the existing
      theories on IDO, it is more appropriate to apply the zero net current conditions
      (formulation F2) and not more restrictive zero net local flux conditions
      (formulation F1) particularly for the case where one considers a nanochannel
      connected to two reservoirs. We pinpoint limitations in the existing literature
      in correctly predicting the diffusioosmotic behavior even for the case where
      formulation F1 is used. We address these limitations and establish that (a) the
      induced electric field is an interplay of the differences in ionic diffusivity,
      the EDL-induced imbalance in ion concentrations, and the advection effects, (b)
      formulation F1 may overpredict or underpredict the electric field and the EOSV
      leading to an overprediction/underprediction of the DOSV and (c) formulation F2
      demonstrates remarkable fluid physics of localized backflows owing to a dominant
      local influence of the COSV, which is missed by formulation F1. We anticipate
      that our theory will provide the first rigorous understanding of nanofluidic IDO
      with applications in multiple areas of low Reynolds number transport such as
      biofluidics, microfluidic separation, and colloidal transport.

PMID- 29594301
TI  - Tuning the structure and magnetic behavior of Ni-Ir-based nanoparticles in ionic
      liquids.
AB  - We report on a simple preparation of extremely small diameter (ca. 2 nm) Ni-Ir
      based NPs using Ni(COD)2 and [Ir(COD)OCH3]2 in 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide (BMIm.NTf2). The prepared NPs had either core
      shell-like or alloy-like structures with the presence of Ni,Ir-oxides, depending
      on the synthetic approach. X-ray diffraction (XRD), Rutherford backscattering
      spectrometry (RBS), high-resolution transmission electron microscopy (HRTEM), X
      ray photoelectron spectroscopy (XPS), extended X-ray absorption fine structure
      (EXAFS), and magnetic measurements are combined to describe the influence of
      nanostructure on the magnetic behavior of these nanosystems. The present findings
      reveal that the alloy NPs display a disordered magnetic state, similar to a spin
      glass (SG)-like system (Tf = 7.2 K). Core-shell NPs are formed by a magnetically
      blocked/unblocked core with a magnetically disordered shell as deduced from the
      two magnetic responses peaking at TB = 75 K and Tf = 5.8 K. Coupling at the core
      shell interface leads to an exchange bias revealed at low temperature as
      horizontal shifts in the hysteresis loops of 0.12 kOe at 2 K.

PMID- 29594303
TI  - A theoretical study on mixtures of amino acid-based ionic liquids.
AB  - Ionic liquid mixtures containing amino acid anions are studied at the microscopic
      level using molecular dynamics simulations. The analysis of relevant features
      such as intermolecular forces (hydrogen bonding), molecular level arrangements,
      and properties of solvation spheres, allowed inferring the structuring of the
      studied mixtures. The effects of mixture compositions and the number of cations
      and anions were analysed in detail. The reported results showed even distribution
      of anions around cations. The absence of microheterogeneities and low deviations
      from ideality are due to the similar mechanism of interaction between the
      considered anions and cations. Likewise, the most relevant features are produced
      by the development of hydrogen bonding between the amino acid carboxylate group
      and hydrogen bond donor sites in the cations.

PMID- 29594302
TI  - A benzoic acid terpyridine-based cyclometalated iridium(iii) complex as a two
      photon fluorescence probe for imaging nuclear histidine.
AB  - A series of two-photon active cyclometalated iridium(iii) complexes (Ir1, Ir2 and
      Ir3) were designed. Ir1 with a two-photon action cross-section of 40 GM in the
      NIR region has been developed for targeting intracellular histidine. Two-photon
      micrographs showed that Ir1 could rapidly and selectively light up the nucleus in
      both fixed and live cells and is capable of displaying nuclear histidine
      distribution in ultra-detail using a super resolution (SR) technique under
      stimulated emission depletion (STED) microscopy.

PMID- 29594304
TI  - Stacking sequences of black phosphorous allotropes and the corresponding few
      layer phosphorenes.
AB  - Possible bulk black phosphorus (BP) allotropes are constructed based on single
      layer BP with various stacking sequences. Our stacking algorithm shows that there
      are eight possible allotropes with two stacking layers in their unit cells
      possessing relatively high symmetries, and six of them are retained after
      structural relaxation using a van der Waals correction of optB88-vdW. The AF, AG,
      and AH bulk structures are presented for the first time. The structural
      relationship of these configurations has been explained via an interlayer
      slipping process. The total energy of the AF allotrope is closest to the most
      stable bulk BP structure (AB stacking) among all explored 2-layer stacked bulk
      structures. The calculated band structure of the AF allotrope using HSE06 shows a
      direct band gap of 0.48 eV with anisotropic electronic structures. We also
      presented six possible BP allotropes with three stacking layers in their unit
      cells. The newly reported AAF and ABC stacked structures show semiconducting and
      metallic features, respectively. After the bulk structures were explored, we
      further built the corresponding few-layer phosphorene structures and investigated
      their electronic properties. The results show that all the few-layer phosphorenes
      show semiconducting features. The AE, AAE, and AEA phosphorenes have indirect
      band gaps while the other explored phosphorenes possess direct band gaps located
      at the Gamma point.

PMID- 29594305
TI  - Spectroscopic properties of high-temperature sintered SrS:0.05%Ce3+ under high
      hydrostatic pressure.
AB  - Luminescence properties of SrS:Ce pellets sintered at 1700  degrees C were
      investigated under high pressure. Two different Ce3+-related emissions were
      confirmed to appear in the blue-green and red parts of the spectrum and were
      shown to shift significantly and linearly to longer wavelengths with increasing
      pressure. Changes in decay times of both emissions were also thoroughly analyzed.
      The results confirmed that Ce3+ ion pairing/clustering occurring due to their
      enhanced mobility at high temperatures is responsible for the appearance of the
      recently reported red Ce3+ emission in sintered SrS:Ce pellets.

PMID- 29594306
TI  - Label-free and sensitive detection of Ochratoxin A based on dsDNA-templated
      copper nanoparticles and exonuclease-catalyzed target recycling amplification.
AB  - Ochratoxin A (OTA) is one of the most toxic mycotoxins and exists in various food
      commodities. Herein, a sensitive fluorescence method was developed for OTA
      detection which combines the advantages of label-free dsDNA-templated copper
      nanoparticles (CuNPs), high selectivity of OTA aptamer and high efficiency of
      exonuclease-catalyzed target recycling amplification. OTA aptamer was hybridized
      with its complementary DNA (cDNA), and the obtained dsDNA acted as the template
      for fluorescent CuNPs. In the presence of its target (OTA), the aptamer prefers
      to form an OTA-aptamer complex in lieu of an aptamer-DNA duplex, which results in
      the dissociation of the aptamer-DNA duplex. The released cDNA and aptamer could
      be digested into mononucleotides by the RecJf exonuclease (single-stranded DNA
      specific exonuclease), and the target was liberated and could participate in the
      next reaction cycle. The above process resulted in the degradation of a large
      amount of template dsDNA, which prevented the synthesis of CuNPs, thus resulting
      in low fluorescence of the system. Based on this strategy, a label-free and
      sensitive detection of OTA was developed with a low detection limit of 5 ng mL-1
      (S/N = 3). Our strategy was further validated and evaluated successfully by
      assaying OTA in real samples. The proposed assay has great potential as an OTA
      quantification method for use in the food safety field.

PMID- 29594307
TI  - Organic titanates: a model for activating rapid room-temperature synthesis of
      shape-controlled CsPbBr3 nanocrystals and their derivatives.
AB  - The application of lead halide perovskite nanocrystals is challenged by the lack
      of strategies in rapid room-temperature synthesis with controlled morphologies.
      Here, we report on an initial study of adopting organic titanates as a model
      activator that promotes rapid room-temperature synthesis of shape-controlled,
      highly luminescent CsPbBr3 nanocrystals and their derivatives.

PMID- 29594308
TI  - Sunlight-charged heterojunction TiO2 and WO3 particle-embedded inorganic
      membranes for night-time environmental applications.
AB  - A metal oxide-heterojunction photocatalyst is developed to harvest sunlight,
      store the energy in electrons, and apply the stored energy in water treatment.
      Light-absorbing nanoparticular and nanotubular TiO2 are hybridized with electron
      storing WO3 at different weight ratios of TiO2 to WO3 (e.g., TW25 represents a
      composite of 25 wt% TiO2 and 75 wt% WO3). The ability of the TW composite to
      utilize the stored electrons is examined for the reduction of hexavalent chromium
      (Cr(vi)). In the photoelectrochemical (PEC) tests, irradiation using simulated
      sunlight (AM 1.5, 100 mW cm-2) leads to a rapid shift in the open-circuit
      potential (OCP) of the TW electrodes to the negative potential region
      (photocharging process). The termination of irradiation causes a gradual shift of
      the OCP to the positive potential region over 20 h (discharging process). Spiked
      Cr(vi) added to the solution with pre-photocharged TW electrodes is efficiently
      removed; the kinetics of this process depends on the TW composition (25, 50, or
      75 wt%), TiO2 morphology (particular or tubular), initial Cr(vi) concentration
      (0.125 or 0.25 ppm), and whether the conditions are aerated or non-aerated. Based
      on this knowledge, TW composite-embedded inorganic membranes are synthesized and
      charged using sunlight. For Cr(vi) removal, single-pass and continuous
      circulation filtration systems are employed. The fraction of Cr(vi) removed from
      the circulation system is ~30% in 4 h, which is 1.5 times that removed using the
      single-pass filtration system (~20%). An X-ray photoelectron spectroscopy
      analysis of the TW membranes used for Cr(vi) removal reveals that Cr is not
      sorbed in the membrane. The W(vi) in WO3 is partially reduced to W(6-x)+ upon
      photocharging and is oxidized during the reduction of Cr(vi), leading to the co
      existence of W6+ and W(6-x)+.

PMID- 29594309
TI  - Hydrogenation of an iridium-coordinated imidazol-2-ylidene ligand fragment.
AB  - An iridium complex featuring a metalated lutidine-derived CNP ligand reacts with
      KOtBu to yield a dimeric species with the two metal centers bound to the opposite
      ligands through the CHN arms. Furthermore, reaction with H2 in the presence of
      KOtBu of the same iridium derivative results in the hydrogenation of the 
      CH[double bond, length as m-dash]CH- imidazolylidene moiety of the complex. NMR
      spectroscopy monitoring of the latter reaction supports the initial formation of
      a dihydride iridium complex containing an imidazolylidene ligand fragment that is
      hydrogenated after prolonged reaction time.

PMID- 29594310
TI  - The carbon chain-selective adenylation enzyme TamA: the missing link between
      fatty acid and pyrrole natural product biosynthesis.
AB  - The marine bacterium Pseudoalteromonas tunicata produces the bipyrrole antibiotic
      tambjamine YP1. This natural product is built from common amino acid and fatty
      acid building blocks in a biosynthetic pathway that is encoded in the tam operon
      which contains 19 genes. The exact role that each of these Tam proteins plays in
      tambjamine biosynthesis is not known. Here, we provide evidence that TamA
      initiates the synthesis and controls the chain length of the essential tambjamine
      fatty amine tail. Sequence analysis suggests the unusual TamA is comprised of an
      N-terminal adenylation (ANL) domain fused to a C-terminal acyl carrier protein
      (ACP). Mass spectrometry analysis of recombinant TamA revealed the surprising
      presence of bound C11 and C12 acyl-adenylate intermediates. Acylation of the ACP
      domain was observed upon attachment of the phosphopantetheine (4'-PP) arm to the
      ACP. We also show that TamA can transfer fatty acids ranging in chain length from
      C6-C13 to an isolated ACP domain. Thus TamA bridges the gap between primary and
      secondary metabolism by linking fatty acid and pyrrole biosynthetic pathways.

PMID- 29594311
TI  - Comparison of Subjective and Objective Measures of Hearing, Auditory Processing,
      and Cognition Among Older Adults With and Without Mild Cognitive Impairment.
AB  - Purpose: The aims of the study were to compare the Cognitive Self-Report
      Questionnaire (CSRQ; Spina, Ruff, & Mahncke, 2006) Hearing and Cognitive subscale
      ratings among older adults with and without probable mild cognitive impairment
      (MCI) and to examine whether self-report, as measured by the CSRQ, is associated
      with objective measures of hearing, auditory processing, and cognition. Method:
      Data analyses included 97 older adults of ages 61-91 years. Participants
      completed the CSRQ self-report measure as well as a battery of objective
      measures, including pure-tone audiometry, degraded speech understanding, temporal
      processing, and memory. Results: Older adults with probable MCI rated their
      cognitive abilities more poorly than those without MCI (p = .002), but ratings of
      hearing and auditory abilities did not differ between the two groups (p = .912).
      Age and CSRQ Hearing subscale ratings explained a significant proportion of
      variance in objective measures of hearing and degraded speech understanding (R2 =
      .39, p < .001). Age, sex, mental status, and CSRQ Cognition subscale ratings
      explained a significant proportion of variance in objective memory performance
      (R2 = .55, p < .001). Conclusions: Taken together, these results suggest that the
      CSRQ is an appropriate self-report measure of hearing, cognition, and some
      aspects of auditory processing for older adults with and without probable MCI.

PMID- 29594312
TI  - The Effect of Partner Reauditorization on Undergraduates' Attitudes Toward a Peer
      Who Communicates With Augmentative and Alternative Communication.
AB  - Purpose: This study compared college students' attitudes toward a peer who used a
      nonelectronic augmentative and alternative communication (AAC) system with and
      without a partner reauditorization strategy and also examined the effect of
      reauditorization on reported (a) ease of understanding the peer who used AAC, (b)
      willingness to engage in interactions with the peer who used AAC, and (c)
      preferences regarding AAC systems. Method: Sixty-four participants completed
      surveys after viewing each of 2 counterbalanced conditions involving a video of a
      peer who communicated using AAC. Mean survey ratings were compared between
      conditions. Results: Participants reported (a) more positive attitudes toward,
      (b) a greater ease in understanding, and (c) an increased willingness to interact
      with the peer who used nonelectronic AAC with partner reauditorization.
      Participants indicated that reauditorization contributed positively to the
      observed conversation. Reported preferences for nonelectronic AAC systems did not
      vary as a function of reauditorization, and most participants reported a
      preference for an electronic speech-generating device when compared with a
      nonelectronic system. Conclusion: Partner reauditorization may play a role in
      improving attitudes that individuals hold about peers who use nonelectronic AAC
      and may contribute to ease of understanding the aided message and increased
      likelihood of peer interactions.

PMID- 29594313
TI  - Automated Language Environment Analysis: A Research Synthesis.
AB  - Purpose: The Language Environment Analysis (LENA(r)) represents a breakthrough in
      automatic speech detection because it makes one's language environment, what
      adults and children actually hear and say, efficiently measurable. The purpose of
      this article was to examine (a) current dimensions of LENA research, (b) LENA's
      sensitivity to differences in populations and language environments, and (c) what
      has been achieved in closing the Word Gap. Method: From electronic and human
      searches, 83 peer-reviewed articles using LENA were identified, and 53 met
      inclusionary criteria and were included in a systematic literature review. Each
      article reported results of 1 study. Results: Originally developed to make
      natural language research more efficient and feasible, systematic review
      identified a broad landscape of relevant LENA findings focused primarily on the
      environments and communications of young children but also older adults and
      teachers. LENA's automated speech indicators (adult input, adult-child
      interaction, and child production) and the audio environment were shown to meet
      high validity standards, including accuracy, sensitivity to individual
      differences, and differences in populations, settings, contexts within settings,
      speakers, and languages. Researchers' own analyses of LENA audio recordings have
      extended our knowledge of microlevel processes in adult-child interaction. To
      date, intervention research using LENA has consisted of small pilot experiments,
      primarily on the effects of brief parent education plus quantitative linguistic
      feedback to parents. Conclusion: Evidence showed that automated analysis has made
      a place in the repertoire of language research and practice. Implications,
      limitations, and future research are discussed.

PMID- 29594314
TI  - Malaysian Congress of Radiology (MCOR) 2018, Malaysian Society of Interventional
      Radiology (MYSIR) 2018, in conjunction with 13th Asian-Australasian Federation of
      Interventional & Therapeutic Neuroradiology (AAFITN) 2018. Kota Kinabalu,
      Malaysia, 7-9 March 2018. Proceedings and abstracts.

PMID- 29594315
TI  - Profiling the immunotoxicity of chemicals based on in vitro evaluation by a
      combination of the Multi-ImmunoTox assay and the IL-8 Luc assay.
AB  - We established a luciferase reporter assay system, the Multi-ImmunoTox Assay
      (MITA), which can evaluate the effects of chemicals on the promoter activities of
      four cytokines: IL-2, IFN-gamma, IL-1beta, and IL-8. We previously reported that
      MITA correctly reflected the change in mRNA of human whole-blood cells treated
      with dexamethasone, cyclosporine, FK506, or several other immunosuppressive
      drugs. In this study, we combined MITA with the IL-8 Luc assay to detect skin
      sensitization chemicals (OECD 442E) (modified MITA: mMITA) and established a data
      set of 60 chemicals examined by mMITA. Using the mMITA results, chemicals can be
      classified based on the lowest observed effect level (LOEL) of chemicals in
      suppressing or augmenting the promoter activities of the four cytokines.
      Moreover, we demonstrated that K-means clustering and hierarchical clustering of
      the 60 chemicals based on the LOEL for their effects on IL-2 and IL-8 promoter
      activities and the judgment by the IL-8 Luc assay resulted in the same 6-cluster
      solution: cluster 1 with preferential suppression of IL-8, cluster 2 with
      suppression of IL-2 and a positive IL-8 Luc assay result, cluster 3 with
      suppression of both IL-2 and IL-8, cluster 4 with no effects on IL-2 or IL-8 and
      a negative IL-8 Luc assay result, cluster 5 with suppression of both IL-2 and IL
      8 and a negative IL-8 Luc assay result, and cluster 6 with preferential
      suppression of IL-8. These data suggest that mMITA is a promising novel high
      throughput approach for detecting unrecognized immunological effects of chemicals
      and for profiling their immunotoxic effects.

PMID- 29594316
TI  - An integrated approach to elucidate signaling pathways of dioscin-induced
      apoptosis, energy metabolism and differentiation in acute myeloid leukemia.
AB  - Although the therapeutics have improved the rates of remission and cure of acute
      myelogenous leukemia (AML) in recent decades, there is still an unmet medical
      need for AML therapies because disease relapses are a major obstacle in patients
      who become refractory to salvage therapy. The development of therapeutic agents
      promoting both cytotoxicity and cell differentiation may provide opportunities to
      improve the clinical outcome. Dioscin-induced apoptosis in leukemic cells was
      identified through death receptor-mediated extrinsic apoptosis pathway. The
      formation of Bak and tBid, and loss of mitochondrial membrane potential were
      induced by dioscin suggesting the activation of intrinsic apoptotsis pathway. A
      functional analysis of transcription factors using transcription factor-DNA
      interaction array and IPA analysis demonstrated that dioscin induced a profound
      increase of protein expression of CCAAT/enhancer-binding protein alpha
      (C/EBPalpha), a critical factor for myeloid differentiation. Two-dimensional gel
      electrophoresis assay confirmed the increase of C/EBPalpha expression. Dioscin
      induced differentiation was substantiated by an increase of CD11b protein
      expression and the induction of differentiation toward
      myelomonocytic/granulocytic lineages using hematoxylin and eosin staining.
      Moreover, both glycolysis and gluconeogenesis pathways after two-dimensional gel
      electrophoresis assay and IPA network enrichment analysis were proposed to
      dioscin action. In conclusion, the data suggest that dioscin exerts its
      antileukemic effect through the upregulation of both death ligands and death
      receptors and a crosstalk activation of mitochondrial apoptosis pathway with the
      collaboration of tBid and Bak formation. In addition, proteomics approach reveals
      an altered metabolic signature of dioscin-treated cells and the induction of
      differentiation of promyelocytes to granulocytes and monocytes in which the
      C/EBPalpha plays a key role.

PMID- 29594318
TI  - Adrenal crisis after first infusion of zoledronic acid: a case report.
AB  - Patients with Addison's disease are at greater risk of having reduced bone
      mineral density and hip fractures and are thus more likely to receive a
      bisphosphonate than their peers. Potent intravenous bisphosphonates could provoke
      an acute phase reaction. An 80-year-old female with Addison's disease received
      her first infusion of zoledronic acid for osteoporosis at our outpatient clinic
      around noon. Despite doubling her usual afternoon hydrocortisone dose, she became
      feverish, nauseous, extremely weak, and hypotensive over the night. When
      transported to the nearest general hospital the next morning, the patient was
      found to have signs of hypovolemic shock and she was admitted to the ICU.
      Crystalloid infusion, followed by dobutamine and norepinephrine drip, had no
      effect. Only after her European emergency card for glucocorticoid cover was
      found, adrenal crisis was recognized, and she was immediately given an
      intravenous bolus of hydrocortisone followed by continuous hydrocortisone
      infusion. The patient rapidly improved and was transferred to a regular ward the
      next day, where hydrocortisone dose was gradually tapered. Our experience might
      suggest that patients with Addison's disease should probably start their
      treatment with zoledronic acid in a hospital setting. Their usual oral dose of
      hydrocortisone should be doubled or even tripled. Careful monitoring of these
      patients seems to be warranted, and intravenous hydrocortisone should be given if
      any symptoms or signs of the imminent adrenal crisis are noted.

PMID- 29594317
TI  - [Prevention of acute kidney injury in critically ill patients : Recommendations
      from the renal section of the DGIIN, OGIAIN and DIVI].
AB  - BACKGROUND: Acute kidney injury (AKI) has both high mortality and morbidity.
      OBJECTIVES: To prevent the occurrence of AKI, current recommendations from the
      renal section of the DGIIN (Deutschen Gesellschaft fur Internistische
      Intensivmedizin und Notfallmedizin), OGIAIN (Osterreichischen Gesellschaft fur
      Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI
      (Deutschen Interdisziplinaren Vereinigung fur Intensiv- und Notfallmedizin) are
      stated. MATERIALS AND METHODS: The recommendations stated in this paper are based
      on the current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, the
      published statements of the "Working Group on Prevention, AKI section of the
      European Society of Intensive Care Medicine" and the expert knowledge and
      clinical experience of the authors. RESULTS: Currently there are no approved
      clinically effective drugs for the prevention of AKI. Therefore the mainstay of
      prevention is the optimization of renal perfusion by improving the mean arterial
      pressure (>65 mm Hg, higher target may be considered in hypertensive patients).
      This can be done by vasopressors, preferably norepinephrine and achieving or
      maintaining euvolemia. Hyperhydration that can lead to AKI itself should be
      avoided. In patients with maintained diuresis this can be done by diuretics that
      are per se no preventive drug for AKI. Radiocontrast enhanced imaging should not
      be withheld from patients at risk for AKI; if indicated, however, the contrast
      media should be limited to the smallest possible volume.

PMID- 29594319
TI  - Outcome of rolled fortified vaginal flap operation on female patients with
      intrinsic sphincteric deficiency: 2-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: We evaluate the 2-year outcome of the rolled
      fortified vaginal flap (RFVF) operation for the treatment of stress urinary
      incontinence (SUI) due to intrinsic sphincteric deficiency (ISD). METHODS: A
      prospective study of 20 women suffering from SUI due to ISD was conducted. All
      patients were subjected to history-taking, clinical examination, cough stress
      test, and urodynamics. Symptom severity and quality of life (QoL) were assessed
      using the Arabic version of the International Consultation on Incontinence
      Questionnaire Urinary Incontinence Short Form (ICIQ-UI-SF). All studied women
      were followed up for 24 months to detect success rate, any postoperative
      complications, and reveal changes in the quality of life. RESULTS: Mean age was
      53 +/- 8 years. Preoperative Valsalva leak point pressure was 50.1 +/- 11.3
      cmH2O. After a follow-up period of 24 months, only 2 patients (10%) showed mild
      stress incontinence with mean VLPP 80+/- 3 cm H2O. Postoperative mean maximum
      flow rate (Q-max) and mean Pdet-Qmax showed no significant difference from the
      preoperative results (P = 0.115 and 0.187 respectively). The quality of life
      domain of the ICIQ-UI-SF decreased significantly from 73.5 +/- 12.1%
      (preoperatively) to 2.6 +/- 8.1% (after a 1-year follow-up), P < 0.001 and then
      showed a slight increase to 4.5 +/- 10.6 at 24 months' follow-up. CONCLUSION: The
      RFVF operation has a success rate of 90% after a 24-month follow-up. It
      significantly improved the quality of life of women with SUI due to ISD.

PMID- 29594320
TI  - Re: Treatment of stress urinary incontinence with a mobile app: factors
      associated with success.

PMID- 29594321
TI  - [Rheumatoid instability in the cervical spine : Diagnostic and therapeutic
      strategies].
AB  - BACKGROUND: The involvement of the cervical spine in rheumatoid arthritis (RA)
      continues to be of clinical importance even in this age of biologics.
      Pathophysiological changes begin with an isolated atlantoaxial subluxation and
      may progress to a complex craniocervical and subaxial instability. The onset of
      cervical myelopathy can occur at any time and leads to a deterioration of the
      prognosis for the patient. THERAPY: Treatment of the rheumatoid cervical spine
      should be aimed at improvement of the symptoms and prevention of further progress
      of the disease. In the case of instability, this is only possible by surgical
      treatment. The increasing usage of biological agents has led to a change in the
      clinical picture of the cervical involvement in RA patients. There are fewer
      patients presenting with isolated atlantoaxial instability. In contrast, the
      number of patients with complex craniocervical and/or subaxial instabilities is
      increasing. Complex cervical instabilities may require a longer fusion from the
      occiput to the upper thoracic spine. Modern operative techniques make this
      complex surgery also possible in severely disabled patients with a high
      comorbidity.

PMID- 29594322
TI  - Letter to the editor in reponse to Louboutin, Wascher, and Neyret in management
      of patellar problems in skeletally mature patients with nail-patella syndrome.
      KSSTA 2017 Oct;25(10):3012-3016. https://doi.org/10.1007/s00167-016-4044-y. Epub
      2016 Feb 12.

PMID- 29594323
TI  - Beach handball is safer than indoor team handball: injury rates during the 2017
      European Beach Handball Championships.
AB  - PURPOSE: Beach handball is a relatively new type of sports, which was derived
      from team handball. Medical issues such as frequency and severity of injury are
      yet unknown. The purpose of this study was to investigate the injury pattern and
      injury rates of this new type of sports. METHODS: This study investigated the
      injury incidence of 30 national teams (10 senior and 20 u-17 teams, 16 men's and
      14 women's teams) participating in the 2017 European Beach Handball
      Championships. Reports on injuries sustained during the senior and u-17 youth
      tournaments were provided by the medical staff of each team. Injury incidence was
      differentiated between age and sex, and between the five field positions
      (goalkeeper, wing, central defender, pivot, and specialist). RESULTS: During the
      tournaments, 87 injuries were recorded yielding an overall injury incidence of
      286.1 per 1000 match hours. Time-loss due to injury was 49.3 per 1000 match
      hours. Senior players had a higher overall injury incidence with 395.3 injuries
      than u-17 players with 205.7 injuries per 1000 h match hours (p < 0.01).
      Comparison of the injury incidence between the two sexes showed 330.23 injuries
      per 1000 h handball exposure for male players and 234.9 injuries for female
      players (n.s.). The most frequent injury type was sprains (21 injuries, 24.1%)
      followed by contusions (19 injuries, 21.8%) and skin abrasions with (15 injuries,
      17.2%). Central defenders and specialists had the highest injury incidence.
      Thighs, ankles, as well as foot and toes (altogether 12 injuries, all 13.8%) were
      the three most frequently injured anatomic sites. CONCLUSIONS: Beach handball
      seems to have a lower incidence of time-loss injuries than that reported for
      indoor team handball. This study is an important basis for developing injury
      prevention strategies in this sports that should focus on thighs, ankles, feet
      and toes. Further research into this new type of sports is essential to identify
      risk factors and to develop adequate injury prevention measures. LEVEL OF
      EVIDENCE: II.

PMID- 29594324
TI  - Under-corrected knees do not fail more than aligned knees at 8 years in fixed
      severe valgus total knee replacement.
AB  - PURPOSES: A fixed severe valgus knee is a surgical challenge. A safe post
      operative Hip-Knee-Ankle angle (HKA) range of 180 degrees  +/- 4 was recommended,
      but recent studies mentioned equal results from outliers of this range.
      Nevertheless, no distinction was made between varus and valgus knees, as well as
      over-corrected or under-corrected knees. Did post-operative nonaligned total knee
      replacements (TKR) from fixed severe valgus knees behave differently from the
      properly aligned population? Did over-corrected knees behave differently from
      under-corrected knees? METHODS: Through a multi-center retrospective cohort
      study, we provided 557 knees of at least 10 degrees  of minimal pre-operative
      valgus; in this population 75 presented a post-operative Hip-Knee-Ankle angle
      (HKA) outside of the 180 degrees  +/- 4 range; 23 of them had at least 5 degrees 
      of varus; 52 of them had at least 5 degrees  of valgus. Median pre-operative HKA
      of the entire cohort was 194 degrees  (range 190-198). Median follow-up was 8
      years (range 5-11); Knee Society Score (KSS) results, HKA, Femoral and Tibial
      Mechanical Angles (FMA, TMA) and complication rates were obtained. The outlier
      group (HKA <= 175 or >= 185) was compared to the control group (HKA 180 +/- 4);
      over-corrected (HKA <= 175) and under-corrected (HKA >= 185) sub-groups were
      individually tested against the control group. RESULTS: The outlier group had a
      lower Final Knee Score than the aligned group (p = 0.023). In the over-corrected
      sub-group, median post-operative FMA was 88 degrees  (SD 4 degrees ) and median
      TMA was 87 degrees  (SD 4 degrees ). The complication rate was higher (p =
      0.019). Knee (p = 0.018), Function (p = 0.034) and Final Knee Scores (p = 0.03)
      were statistically lower than in the control group. In the under-corrected sub
      group, mean post-operative FMA was 93 degrees  (SD 2 degrees ) and mean TMA was
      91 degrees  (SD 2 degrees ). The complication rate was lower (p = 0.019) and
      there was no difference with the control group concerning KSS. CONCLUSIONS: In
      case of pre-operative fixed severe valgus knee, one should avoid over-correcting
      HKA angle and especially the TMA. Over-correction of a severe preoperative valgus
      in a post-operative varus was prejudicial for TKA survival. Keeping a severe
      valgus knee in low valgus to avoid using a more constrained implant and/or
      ligament releases will not decrease the 5-10 year implant survival and functional
      scores. LEVEL OF EVIDENCE: Level IV-Case series.

PMID- 29594326
TI  - Dysregulation of autophagy in rat liver with mitochondrial DNA depletion induced
      by the nucleoside analogue zidovudine.
AB  - The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV
      infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect
      relationship between mtDNA status alterations and autophagy has been reported.
      Both events are common in several liver diseases, including hepatocellular
      carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA
      depletion induced by AZT administration in drinking water for 35 days. AZT at a
      concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased
      mtDNA levels in rat liver and extrahepatic tissues. In liver, mtDNA-encoded
      cytochrome c oxidase 1 protein levels were decreased. Although serum biomarkers
      of liver and kidney toxicity remained unaltered, beta-hydroxybutyrate levels were
      increased in liver of AZT-treated rats. Moreover, autophagy was dysregulated at
      two levels: (i) decreased induction signalling of this process as indicated by
      increases in autophagy inhibitors activity (AKT/mTOR), and absence of changes
      (Beclin-1, Atg5, Atg7) or decreases (AMPK/ULK1) in the expression/activity of pro
      autophagy proteins; and (ii) reduced autophagosome degradation as indicated by
      decreases in the lysosome abundance (LAMP2 marker) and the transcription factor
      TFEB controlling lysosome biogenesis. This resulted in increased autophagosome
      abundance (LC3-II marker) and accumulation of the protein selectively degraded by
      autophagy p62, and the transcription factor Nrf2 in liver of AZT-treated rats.
      Nrf2 was activated as indicated by the up-regulation of antioxidant target genes
      Nqo1 and Hmox-1. In conclusion, rat liver with AZT-induced mtDNA depletion
      presented dysregulations in autophagosome formation and degradation balance,
      which results in accumulation of these structures in parenchymal liver cells,
      favouring hepatocarcinogenesis.

PMID- 29594325
TI  - Can inadequate acromiohumeral distance improvement and poor posterior remnant
      tissue be the predictive factors of re-tear? Preliminary outcomes of arthroscopic
      superior capsular reconstruction.
AB  - PURPOSE: The factors affecting the anatomical and functional outcomes of
      arthroscopic superior capsular reconstruction (ASCR) were investigated in this
      study. Continuity between the posterior remnant tissue and graft, as well as
      medial-to-lateral anatomical graft continuity, might play a vital role in
      shoulder stability and functional recovery, which could be correlated with
      postoperative factors such as the acromiohumeral distance (AHD). METHODS: Thirty
      two patients (36 shoulders) who underwent ASCR were included. The follow-up
      period was 24.8 +/- 6.9 months. The relationship between graft continuity and
      preoperative, intraoperative, and postoperative factors that could affect the
      clinical and radiological outcomes of ASCR were investigated. RESULTS: The
      American Shoulder and Elbow Surgeons score increased from 50.3 +/- 9.1 points
      preoperatively to 84.0 +/- 5.0 points postoperatively (p < 0.01), and the
      Constant score increased from 56.3 +/- 9.0 to 82.8 +/- 5.6 points (p = 0.02). Re
      tearing occurred in 13 patients during the postoperative follow-up period. The re
      tear rate was relatively high (36.1%). The gap between the immediate
      postoperative and preoperative AHDs was 1.6 +/- 2.2 mm in the re-tear (+) group
      and 3.8 +/- 2.8 mm in the re-tear (-) group (p = 0.02). The integrity of the
      posterior remnant tissue had a statistically significant and different re-tear
      rate (p < 0.01). CONCLUSION: Care should be taken in patients with inadequate AHD
      improvement and poor posterior remnant tissue immediately postoperatively,
      because the possibility of re-tearing is high. Therefore, better results can be
      predicted when considering these factors at the time of surgery. LEVEL OF
      EVIDENCE: IV.

PMID- 29594327
TI  - Coffee consumption, metabolic syndrome and clinical severity of psoriasis: good
      or bad stuff?
AB  - Despite the wide consumption of coffee, its anti-inflammatory effect on clinical
      severity of psoriasis is still debatable. The aim of this study was to evaluate
      the association between the coffee consumption and clinical severity of psoriasis
      in a sample of patients stratified according to the presence of the metabolic
      syndrome (MetS) and smoking. This cross-sectional case-control observational
      study was conducted on 221 treatment-naive psoriatic patients. Lifestyle habits,
      anthropometric measures, clinical and biochemical evaluations were obtained.
      Clinical severity of psoriasis was assessed by Psoriasis Area and Severity Index
      (PASI) score. Data on energy caloric intake and coffee consumption were collected
      using a 7-day food diary record. The coffee consumption was analyzed as coffee
      intake (consumers and non-consumers) and daily servings (range 0-4 servings/day).
      Coffee consumers have a lower PASI score vs non-consumers (p < 0.001). The lowest
      PASI score and MetS prevalence were found in patients consuming 3 cups of
      coffee/day (p < 0.001), which was also the most common daily serving (34.8%),
      whereas the highest PASI score was found among those drinking >= 4 cups/day.
      Grouping the case patients according to smoking and MetS, the best odds of PASI
      score was observed in those drinking 3 cups of coffee per day and no smokers,
      after adjusting for total energy intake (OR 74.8; p < 0.001). As a novel finding,
      we reported a negative association between coffee intake, MetS prevalence and
      clinical severity of psoriasis. The evaluation of the anti-inflammatory effect of
      coffee on clinical severity of psoriasis, whose metabolic risk increases along
      with its clinical severity, could be of great importance from a public health
      perspective.

PMID- 29594328
TI  - Spinal postural changes during the modified Matthiass test in healthy children :
      Interday and interrater reliability of dynamic rasterstereographic measurements.
AB  - OBJECTIVE: The Matthiass test serves to identify postural insufficiencies by
      evaluating the sagittal posture but this subjective assessment may be responsible
      for different reports on the prevalence of postural insufficiencies in children.
      Previously, rasterstereography was used to objectify this clinical test. Until
      now, the coupling of the Matthiass test with rasterstereography has not yet been
      applied to children and the reliability is unknown; therefore, the objective of
      our study was to provide interday and interrater reliability of
      rasterstereographic measurements during dynamic (modified Matthiass test) and
      static trials (only interday) in healthy children. METHODS: Trunk inclination,
      kyphotic, and lordotic angles were measured using rasterstereography during
      static and dynamic trials (modified Matthiass test: 90 degrees  shoulder flexion,
      hand-held load, 5% of body weight). Intraclass correlation coefficients (ICC)
      were calculated using a two-way mixed model (absolute agreement, average
      measure). RESULTS: In this study 21 healthy children were assessed (age range 10
      12 years). Dynamic rasterstereographic measurements showed fair to good interday
      and interrater reliability (ICC 0.46-0.70) and static measurements good to
      excellent interday reliability (ICC 0.63-0.91). CONCLUSION: Dynamic
      rasterstereography during the modified Matthiass test furnishes reliable data
      serving to objectify spinal changes of healthy children and detect postural
      insufficiencies. Additional efforts are needed to investigate how the early
      detection of postural insufficiencies can help to prevent back pain in children,
      adolescents and adults.

PMID- 29594329
TI  - Correction to: Spanish transcultural adaptation and validation of the English
      version of the compliance questionnaire in rheumatology.
AB  - In the original published article, the family name was incorrectly tagged for two
      co-authors. The correct family names of authors Jose Ramon Maneiro Fernandez is
      Maneiro Fernandez and Alejandro Souto Vilas is Souto Vilas.

PMID- 29594330
TI  - Can the world's favorite fruit, tomato, provide an effective biosynthetic chassis
      for high-value metabolites?
AB  - Tomato has a relatively short growth cycle (fruit ready to pick within 65-85 days
      from planting) and a relatively high yield (the average for globe tomatoes is 3-9
      kg fruit per plant rising to as much as 40 kg fruit per plant). Tomatoes also
      produce large amounts of important primary and secondary metabolites which can
      serve as intermediates or substrates for producing valuable new compounds. As a
      model crop, tomato already has a broad range of tools and resources available for
      biotechnological applications, either increased nutrients for health-promoting
      biofortified foods or as a production system for high-value compounds. These
      advantages make tomato an excellent chassis for the production of important
      metabolites. We summarize recent achievements in metabolic engineering of tomato
      and suggest new candidate metabolites which could be targets for metabolic
      engineering. We offer a scheme for how to establish tomato as a chassis for
      industrial-scale production of high-value metabolites.

PMID- 29594331
TI  - Extracellular vesicle-mediated MHC cross-dressing in immune homeostasis,
      transplantation, infectious diseases, and cancer.
AB  - Eukaryotic cells employ different types of extracellular vesicles (EVs) to
      exchange proteins, mRNAs, non-coding regulatory RNAs, carbohydrates, and lipids.
      Cells of the immune system, in particular antigen (Ag)-presenting cells (APCs),
      acquire major histocompatibility complex (MHC) class I and II molecules loaded
      with antigenic peptides from leukocytes and tissue parenchymal and stromal cells,
      through a mechanism known as MHC cross-dressing. Increasing evidence indicates
      that cross-dressing of APCs with pre-formed Ag-peptide/MHC complexes (pMHCs) is
      mediated via passage of clusters of EVs with characteristics of exosomes. A
      percentage of the transferred EVs remain attached to the acceptor APCs, with the
      appropriate orientation, at sufficient concentration within localized areas of
      the plasma membrane, and for sufficient time, so the preformed pMHCs carried by
      the EVs are presented without further processing, to cognate T cells. Although
      its biological relevance is not fully understood, numerous studies have
      demonstrated that MHC cross-dressing of APCs represents a pathway of Ag
      presentation of acquired pre-formed pMHCs to T cells-alternative to direct and
      cross-presentation-participate in immune homeostasis and T cell tolerance, cross
      regulate alloreactive T cells with different MHC restricted specificities, and is
      a mechanism of Ag spreading for autologous, allogeneic, microbial, tumor, or
      vaccine-delivered Ags. Here, we compare MHC cross-dressing with other mechanisms
      and terminologies used for pMHC transfer, including trogocytosis. We discuss the
      experimental evidence, mostly from in vitro and ex vivo studies, of the role of
      MHC cross-dressing of APCs via EVs in positive or negative regulation of T cell
      immunity in the steady state, transplantation, microbial diseases, and cancer.

PMID- 29594332
TI  - Wnt/beta-catenin signaling mediates the suppressive effects of diallyl trisulfide
      on colorectal cancer stem cells.
AB  - PURPOSE: Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC)
      initiation, growth, and metastasis. Garlic-derived organosulfur compound diallyl
      trisulfide (DATS) possesses cancer suppressive properties. Wnt/beta-catenin
      signaling is a key target for CSCs inhibition. However, the interventional effect
      of DATS on colorectal CSCs has not been clarified. We aimed to illustrate the
      regulation of Wnt/beta-catenin in DATS-induced colorectal CSCs inhibition.
      METHODS: Serum-free medium culture was used to enrich colorectal CSCs. SW480 and
      DLD-1 sphere-forming cells were treated with different concentrations of DATS for
      5 days; LiCl and beta-catenin plasmids were used to stimulate the activity of
      Wnt/beta-catenin pathway. The size and number of colonspheres were detected by
      tumorsphere formation assay; the expression of colorectal CSCs-related genes was
      detected by Western blotting and qRT-PCR; the capacities of colorectal CSCs
      proliferation and apoptosis were detected by Cell Counting Kit-8, Hoechst 33258
      cell staining and flow cytometry, respectively. RESULTS: The levels of colorectal
      CSCs markers were elevated in the tumorspheres cells. DATS efficiently suppressed
      the activity of colorectal CSCs, as evidenced by reducing the size and number of
      colonspheres, decreasing the expression of colorectal CSCs markers, promoting
      apoptosis and inhibiting the proliferation of colorectal CSCs. Moreover, DATS
      suppressed the activity of Wnt/beta-catenin pathway, while upregulation of
      Wnt/beta-catenin diminished the inhibitory effect of DATS on colorectal CSCs.
      CONCLUSIONS: Wnt/beta-catenin pathway mediates DATS-induced colorectal CSCs
      suppression. These findings support the use of DATS for targeting colorectal
      CSCs.

PMID- 29594333
TI  - The effectiveness of the low-power laser and kinesiotaping in the treatment of
      carpal tunnel syndrome, a pilot study.
AB  - In mild and moderate cases of carpal tunnel syndrome (CTS), the conservative
      approach is suggested. The purpose of this study is to assess and compare the
      effect of low-power laser versus the combination of low-power laser and
      kinesiotaping on pain, muscle strength, functionality, and electrophysiologic
      parameters in the patients with CTS. The study was planned as single-blind,
      prospective, randomized control. 64 hands diagnosed with CTS were included in the
      study. The patients were randomly divided into three groups by closed envelope
      method. Low-power laser therapy was applied to Group 1 (21 hands), kinesiotaping
      and low-power laser therapy in group 2 (22 hands), sham laser therapy in Group 3
      (21 hands). All patients were assessed by visual numeric pain scale (VNS), hand
      grip strength (HGS), finger pinch strength (FPS), the Boston Carpal Tunnel
      Syndrome Questionnaire (BCTSQ), before treatment, after treatment (3rd week), and
      after (12th week) 3 months the treatment with the same physician. Motor and
      sensory nerve conduction studies were performed with electroneuromyography (ENMG)
      before the treatment (0th week) and at the end of the 12th week. Comparison of
      the group 1 with the group 3 showed significantly better improvement in the
      former in VNS, BCTSQ at 3rd week and 12th week compared to 0th week, and in FPS
      and HGS at 3rd week. Comparison of the group 2 with the group 3 showed
      significantly better improvement in the former VNS, BCTSQ, FPS and HGS at 3rd and
      12th week compared to 0th week. When Group 1 and Group 2 were compared there was
      no statistically significant difference in any parameters in the 3rd week, but
      there was a statistically significant difference in favor of group 2 in FPS and
      HGS parameters at the 12th week. We have found that the kinesiotaping method
      applied with low-power laser treatment does not provide any additional benefit to
      the low-power laser treatment in the short term, however, in the long term, the
      increase in the HGS and FPS has occurred. In conclusion, low-power laser and
      kinesiotaping method in the treatment of CTS may be an effective and reliable
      treatment option in clinical parameters.

PMID- 29594334
TI  - [Different mortality after surgery and stereotactic body radiotherapy for early
      stage non-small-cell lung cancer].

PMID- 29594335
TI  - The retromolar canals and foramina: radiographic observation and application to
      oral surgery.
AB  - PURPOSE: The retromolar canal (RMC) and foramen (RMF) are anatomic variants in
      the retromolar area of the mandible. The purpose of this study was to clarify the
      relationship between the RMC and RMF and related complications, and to reveal how
      the RMC could impact the mandibular anatomy using cone-beam computed tomography
      (CBCT) and panoramic images (PAN). MATERIALS AND METHODS: CBCT and PAN images of
      50 patients were retrospectively analyzed to investigate the morphology of the
      RMC and RMF, and their impact on impacted third molar surgery and orthognathic
      surgery. RESULTS: In PAN images, neither the RMC nor RMF was detected. In CBCT
      images, the RMCs were detected in 26% (13/50) of the patients. A double RMC was
      detected on one side of one patient. The diameter of the RMC ranged from 0.8 to
      2.9 mm (mean; 1.5 +/- 0.6 mm), and the RMF ranged from 0.6 to 2.3 mm (mean; 1.1
      +/- 0.5 mm). No patients experienced unexpected bleeding. Unilateral
      postoperative hypoesthesia of the buccal gingiva in the molar region was reported
      in 6.7% of patients with the RMC. CONCLUSIONS: Hypoesthesia of the buccal gingiva
      in the lower molar region may be the main complication when the RMC is damaged.

PMID- 29594336
TI  - A rare case of atypical thoracodorsal artery: a challenge for flap
      reconstruction.
AB  - The thoracodorsal artery mainly supplies the latissimus dorsi muscle. Anatomical
      details pertaining to the origin and distribution of thoracodorsal artery are
      important because the latissimus dorsi myocutaneous flap is one of the most
      reliable and versatile flaps used in reconstructive surgery. Atypical origin and
      course of the thoracodorsal artery is, therefore, a challenge for flap
      reconstruction surgeries. In the present case, we report multiple variations in
      the branching pattern of axillary artery. The thoracodorsal artery had an unusual
      origin from the second part of axillary artery. The trunk of thoracoacromial
      artery was absent. The thoracodorsal artery after its origin, descended downwards
      over the lateral pectoral region lying deep to pectoralis minor but superficial
      to teres major muscles. It terminated by supplying the latissimus dorsi muscle.
      Due to the presence of atypical thoracodorsal branch, the subscapular artery
      continued as the circumflex scapular artery.

PMID- 29594337
TI  - Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for
      acute myeloid leukemia.
AB  - PURPOSE: Acute myeloid leukemia (AML) is a heterogeneous disease with poor
      outcomes. Despite increased evidence shows that dysregulation of histone
      modification contributes to AML, specific drugs targeting key histone modulators
      are not applied in the clinical treatment of AML. Here, we investigated whether
      targeting KDM6B, the demethylase of tri-methylated histone H3 lysine 27
      (H3K27me3), has a therapeutic potential for AML. METHODS: A KDM6B-specific
      inhibitor, GSK-J4, was applied to treat the primary cells from AML patients and
      AML cell lines in vitro and in vivo. RNA-sequencing was performed to reveal the
      underlying mechanisms of inhibiting KDM6B for the treatment of AML. RESULTS: Here
      we observed that the mRNA expression of KDM6B was up-regulated in AML and
      positively correlated with poor survival. Treatment with GSK-J4 increased the
      global level of H3K27me3 and reduced the proliferation and colony-forming ability
      of primary AML cells and AML cell lines. GSK-J4 treatment significantly induced
      cell apoptosis and cell-cycle arrest in Kasumi-1 cells, and displayed a
      synergistic effect with cytosine arabinoside. Notably, injection of GSK-J4
      attenuated the disease progression in a human AML xenograft mouse model in vivo.
      Treatment with GSK-J4 predominantly resulted in down-regulation of DNA
      replication and cell-cycle-related pathways, as well as abrogated the expression
      of critical cancer-promoting HOX genes. ChIP-qPCR validated an increased
      enrichment of H3K27me3 in the transcription start sites of these HOX genes.
      CONCLUSIONS: In summary, our findings suggest that targeting KDM6B with GSK-J4
      has a therapeutic potential for the treatment of AML.

PMID- 29594338
TI  - Macro- and micromechanical remodelling in the fish atrium is associated with
      regulation of collagen 1 alpha 3 chain expression.
AB  - Numerous pathologies lead to remodelling of the mammalian ventricle, often
      associated with fibrosis. Recent work in fish has shown that fibrotic remodelling
      of the ventricle is 'reversible', changing seasonally as temperature-induced
      changes in blood viscosity alter haemodynamic load on the heart. The atrial
      response to varying haemodynamic load is less understood in mammals and
      completely unexplored in non-mammalian vertebrates. To investigate atrial
      remodelling, rainbow trout were chronically cooled (from 10 +/- 1 to 5 +/- 1 
      degrees C) and chronically warmed (from 10 +/- 1 to 18 +/- 1  degrees C) for a
      minimum of 8 weeks. We assessed the functional effects on compliance using ex
      vivo heart preparations and atomic force microscopy nano-indentation and found
      chronic cold increased passive stiffness of the whole atrium and micromechanical
      stiffness of tissue sections. We then performed histological, biochemical and
      molecular assays to probe the mechanisms underlying functional remodelling of the
      atrial tissue. We found cooling resulted in collagen deposition which was
      associated with an upregulation of collagen-promoting genes, including the fish
      specific collagen I alpha 3 chain, and a reduction in gelatinase activity of
      collagen-degrading matrix metalloproteinases (MMPs). Finally, we found that
      cooling reduced mRNA expression of cardiac growth factors and hypertrophic
      markers. Following long-term warming, there was an opposing response to that seen
      with cooling; however, these changes were more moderate. Our findings suggest
      that chronic cooling causes atrial dilation and increased myocardial stiffness in
      trout atria analogous to pathological states defined by changes in preload or
      afterload of the mammalian atria. The reversal of this phenotype following
      chronic warming is particularly interesting as it suggests that typically
      pathological features of mammalian atrial remodelling may oscillate seasonally in
      the fish, revealing a more dynamic and plastic atrial remodelling response.

PMID- 29594339
TI  - Obesogenic habits among children and their families in response to initiation of
      gluten-free diet.
AB  - : Initiation of a lifelong, gluten-free diet (GFD) in children with celiac
      disease (CD) influences the child's life in many ways. The aim of this study was
      to assess the influence of GFD on the child and his/her family's eating habits
      and lifestyle behaviors. To study this, we asked children and their parents
      completed the Family Eating and Activity Habits Questionnaire (FEAHQ) at the time
      of diagnosis of CD and at least 6 months after initiation of GFD and a
      questionnaires assessing symptoms related to CD and adherence to the GFD diet. We
      analyzed questionnaires from 40 children with CD and their families. There were
      21 females, ranging in age from 4 to 15.7 years (median age 7.4 years+/-2.8
      years). The control group comprised 15 healthy children. After initiation of GFD
      the family ate more junk food including snacks and candies (p = 0.05), with the
      significant change reported by children and fathers (p = 0.001 and 0.03
      respectively). All family members in the control group had significantly less
      snacks. Parents and children reported a significant increase in obesogenic eating
      styles, such as eating from the cooking pot and eating while doing other
      activities (mothers, p = 0.001; fathers, 0.02; and children, 0.02 respectively).
      CONCLUSIONS: Our study shows that initiation of GFD in children with CD leads to
      changes in eating habits and staple food eating that may lead to a more
      obesogenic environment. Care givers, pediatricians, gastroenterologists, and
      dieticians alike should be aware of these implications and educate families
      towards a healthier lifestyle and diet beyond the GFD itself. What's Known: *
      Gluten-free diet has been shown to affect various psychosocial aspects of
      children with celiac disease. * Obesity and celiac are associated. What is New: *
      Initiation of gluten-free diet led to increased eating of junk food both in the
      patient and his/her family. * After initiation of GFD pro-obesogenic eating
      habits is increased.

PMID- 29594340
TI  - Work ability score of solvent-exposed workers.
AB  - PURPOSE: Occupational chronic solvent encephalopathy (CSE), characterized by
      neurocognitive dysfunction, often leads to early retirement. However, only the
      more severe cases are diagnosed with CSE, and little is known about the work
      ability of solvent-exposed workers in general. The aim was to study memory and
      concentration symptoms, work ability and the effect of both solvent-related and
      non-occupational factors on work ability, in an actively working solvent-exposed
      population. METHODS: A questionnaire on exposure and health was sent to 3640
      workers in four solvent-exposed fields, i.e. painters and floor-layers, boat
      builders, printers, and metal workers. The total number of responses was 1730. We
      determined the work ability score (WAS), a single question item of the Work
      Ability Index, and studied solvent exposure, demographic factors, Euroquest
      memory and concentration symptoms, chronic diseases, and employment status using
      univariate and multivariate analyses. The findings were compared to those of a
      corresponding national blue-collar reference population (n = 221), and a small
      cohort of workers with CSE (n = 18). RESULTS: The proportion of workers with
      memory and concentration symptoms was significantly associated with solvent
      exposure. The WAS of solvent-exposed workers was lower than that of the national
      blue-collar reference group, and the difference was significant in the oldest age
      group (those aged over 60). Solvent-exposed worker's WAS were higher than those
      of workers diagnosed with CSE. The WAS were lowest among painters and floor
      layers, followed by metal workers and printers, and highest among boat builders.
      The strongest explanatory factors for poor work ability were the number of
      chronic diseases, age and employment status. Solvent exposure was a weak
      independent risk factor for reduced WAS, comparable to a level of high alcohol
      consumption. CONCLUSIONS: Even if memory and concentration symptoms were
      associated with higher solvent exposure, the effect of solvents on self
      experienced work ability was relatively weak. This in line with the improved
      occupational hygiene and reduced solvent exposure levels in industrialized
      countries, thus the effect may be stronger in high-level exposure environments.
      As a single question, WAS is easily included, applicable, and recommendable in
      occupational screening questionnaires.

PMID- 29594341
TI  - Anaerobic bacteria in wastewater treatment plant.
AB  - PURPOSE: The objective of this study was to assess exposure to anaerobic bacteria
      released into air from sewage and sludge at workplaces from a wastewater
      treatment plant (WWTP). METHODS: Samples of both sewage and sludge were collected
      at six sampling points and bioaerosol samples were additionally collected (with
      the use of a 6-stage Andersen impactor) at ten workplaces covering different
      stages of the technological process. Qualitative identification of all isolated
      strains was performed using the biochemical API 20A test. Additionally, the
      determination of Clostridium pathogens was carried out using 16S rRNA gene
      sequence analysis. RESULTS: The average concentration of anaerobic bacteria in
      the sewage samples was 5.49 * 104 CFU/mL (GSD = 85.4) and in sludge-1.42 * 106
      CFU/g (GSD = 5.1). In turn, the average airborne bacterial concentration was at
      the level of 50 CFU/m3 (GSD = 5.83) and the highest bacterial contamination (4.06
      * 103 CFU/m3) was found in winter at the bar screens. In total, 16 bacterial
      species were determined, from which the predominant strains belonged to
      Actinomyces, Bifidobacterium, Clostridium, Propionibacterium and
      Peptostreptococcus genera. The analysis revealed that mechanical treatment
      processes were responsible for a substantial emission of anaerobic bacteria into
      the air. In both the sewage and air samples, Clostridium perfringens pathogen was
      identified. CONCLUSIONS: Anaerobic bacteria were widely present both in the
      sewage and in the air at workplaces from the WWTP, especially when the
      technological process was performed in closed spaces. Anaerobic bacteria formed
      small aggregates with both wastewater droplets and dust particles of sewage
      sludge origin and as such may be responsible for adverse health outcomes in
      exposed workers.

PMID- 29594342
TI  - Defining microbial community composition and seasonal variation in a sewage
      treatment plant in India using a down-flow hanging sponge reactor.
AB  - The characteristics of the microbial community in a practical-scale down-flow
      hanging sponge (DHS) reactor, high in organic matter and sulfate ion
      concentration, and the seasonal variation of the microbial community composition
      were investigated. Microorganisms related to sulfur oxidation and reduction (2
      27%), as well as Leucobacter (7.50%), were abundant in the reactor. Anaerobic
      bacteria (27-38% in the first layer) were also in abundance and were found to
      contribute to the removal of organic matter from the sewage in the reactor. By
      comparing the Simpson index, the abundance-based coverage estimator (ACE) index,
      and the species composition of the microbial community across seasons
      (summer/dry, summer/rainy, autumn/dry, and winter/dry), the microbial community
      was found to change in composition only during the winter season. In addition to
      the estimation of seasonal variation, the difference in the microbial community
      composition along the axes of the DHS reactor was investigated for the first
      time. Although the abundance of each bacterial species differed along both axes
      of the reactor, the change of the community composition in the reactor was found
      to be greater along the vertical axis than the horizontal axis of the DHS
      reactor.

PMID- 29594343
TI  - Heat and light stresses affect metabolite production in the fruit body of the
      medicinal mushroom Cordyceps militaris.
AB  - Cordyceps militaris is a highly valued edible and medicinal fungus due to its
      production of various metabolites, including adenosine, cordycepin, N6-(2
      hydroxyethyl)-adenosine, and carotenoids. The contents of these metabolites are
      indicative of the quality of commercially available fruit body of this fungus. In
      this work, the effects of environmental abiotic factors, including heat and light
      stresses, on the fruit body growth and metabolite production in C. militaris were
      evaluated during the late growth stage. The optimal growth temperature of C.
      militaris was 20  degrees C. It was found that a heat stress of 25  degrees C for
      5-20 days during the late growth stage significantly promoted cordycepin and
      carotenoid production without affecting the biological efficiency. Light stress
      at 6000 lx for 5-20 days during the late growth stage significantly promoted
      cordycepin production but decreased the carotenoid content. Both heat and light
      stresses promoted N6-(2-hydroxyethyl)-adenosine production. In addition, gene
      expression analysis showed that there were simultaneous increases in the
      expression of genes encoding a metal-dependent phosphohydrolase (CCM_04437) and
      ATP phosphoribosyltransferase (CCM_04438) that are involved in the cordycepin
      biosynthesis pathway, which was consistent with the accumulation of cordycepin
      during heat stress for 5-20 days. A positive weak correlation between the
      cordycepin and adenosine contents was observed with a Pearson correlation
      coefficient of 0.338 (P < 0.05). The results presented herein provide a new
      strategy for the production of a superior quality fruit body of C. militaris and
      contribute to further elucidation of the effects of abiotic stress on metabolite
      accumulation in fungi.

PMID- 29594344
TI  - A key residue for the substrate affinity enhancement of a thermophilic endo
      polygalacturonase revealed by computational design.
AB  - Protein engineering has been a research hotspot to improve the catalytic
      efficiency of industrially important enzymes. In the present study, a novel
      computational strategy was developed to in silico screen mutants with enhanced
      binding interaction between enzyme and substrate as well as catalytic efficiency.
      Through homology modeling and molecular dynamics (MD) simulation, four key
      residues related to substrate binding were identified in the endo
      polygalacturonase BiPG28A from Bispora sp. MEY-1. Further analyses of the
      conformation, hydrogen bond interactions, and binding free energy revealed that
      lysine at position 129 (subsite - 2) has the strongest affinity to substrate.
      Biochemical and calorimetry experiments confirmed the functional role of Lys129
      in substrate binding through non-covalent interactions. The common role of Lys129
      was also verified in another GH28 endo-polygalacturonase. Distinguished from
      other protein engineering strategies involving structure resolution and
      construction of certain enzymes, this computational strategy represents an
      insightful and efficient approach to develop a "designed" enzyme with
      significantly enhanced binding affinity and catalytic efficiency.

PMID- 29594345
TI  - Ubc7/Ube2g2 ortholog in Entamoeba histolytica: connection with the plasma
      membrane and phagocytosis.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) and unfolded protein
      response (UPR) pathways are important for quality and quantity control of
      membrane and secretory proteins. We have identified orthologs of ER-associated
      ubiquitin conjugating enzymes (E2s) Ubc6/Ube2j2 and Ubc7/Ube2g2, ubiquitin
      ligases (E3) Hrd1 and GP78/AMFR, and sensor of UPR, Ire1 in E. histolytica that
      show conservation of important features of these proteins. Biochemical
      characterization of the ortholog of ERAD E2, Ubc7/Ube2g2 (termed as EhUbc7), was
      carried out. This E2 was transcriptionally upregulated several folds upon
      induction of UPR with tunicamycin. Ire1 ortholog was also upregulated upon UPR
      induction suggesting a linked UPR and ERAD pathway in this organism. EhUbc7
      showed enzymatic activity and, similar to its orthologs in higher eukaryotes,
      formed polyubiquitin chains in vitro and localized to both cytoplasm and
      membranes. However, unlike its ortholog in higher eukaryotes, it also showed
      localization to the plasma membrane along with calreticulin. Inactivation of
      EhUbc7 significantly inhibited erythrophagocytosis, suggesting a novel function
      that has not been reported before for this E2. No change in growth, motility, or
      cell-surface expression of Gal/GalNAC lectin was observed due to inactivation of
      EhUbc7. The protein was present in the phagocytic cups but not in the phagosomes.
      A significant decrease in the number of phagocytic cups in inactive EhUbc7
      expressing cells was observed, suggesting altered kinetics of phagocytosis. These
      findings have implications for evolutionary and mechanistic understanding of
      connection between phagocytosis and ER-associated proteins.

PMID- 29594346
TI  - Bulk tank milk prevalence and production losses, spatial analysis, and predictive
      risk mapping of Ostertagia ostertagi infections in Mexican cattle herds.
AB  - This study investigated the prevalence, production losses, spatial clustering,
      and predictive risk mapping in different climate zones in five states of Mexico.
      The bulk tank milk samples obtained between January and April 2015 were analyzed
      for antibodies against Ostertagia ostertagi using the Svanovir ELISA. A total of
      1204 farm owners or managers answered the questionnaire. The overall herd
      prevalence and mean optical density ratio (ODR) of parasite were 61.96% and 0.55,
      respectively. Overall, the production loss was approximately 0.542 kg of milk per
      parasited cow per day (mean ODR = 0.92, 142 farms, 11.79%). The spatial disease
      cluster analysis using SatScan software indicated that two high-risk clusters
      were observed. In the multivariable analysis, three models were tested for
      potential association with the ELISA results supported by climatic,
      environmental, and management factors. The final logistic regression model based
      on both climatic/environmental and management variables included the factors
      rainfall, elevation, land surface temperature (LST) day, and parasite control
      program that were significantly associated with an increased risk of infection.
      Geostatistical kriging was applied to generate a risk map for the presence of
      parasite in dairy cattle herds in Mexico. The results indicate that climatic and
      meteorological factors had a higher potential impact on the spatial distribution
      of O. ostertagi than the management factors.

PMID- 29594347
TI  - Nestedness in assemblages of helminth parasites of bats: a function of geography,
      environment, or host nestedness?
AB  - Nested subsets occur in ecological communities when species-poor communities are
      subsets of larger, species-rich communities. Understanding this pattern can help
      elucidate species colonization abilities, extinction risks, and general
      structuring of biological communities. Here, we evaluate nestedness in a poorly
      studied host-parasite system, bats and their helminths, across the Japanese
      archipelago and within its different bioclimatic regions. We hypothesized that
      (1) if helminth communities are nested across geographic sites at the level of
      the archipelago, then broad-scale processes, like colonization-extinction
      dynamics, mainly structure parasite assemblages; (2) if helminth communities are
      nested across geographic sites at the level of the bioclimatic region, then fine
      scale environmental variation plays a significant role in species nestedness; (3)
      if helminth community nestedness mirrors host species nestedness, then
      communities are nested because the habitats they occupy are nested; and (4) if
      nestedness does not occur or if it is not correlated with any geographical or
      host data, then passive sampling could be responsible for the patterns of
      parasite assemblage in our sample. We found that helminth communities were nested
      across host species throughout the archipelago but, when considering each
      bioclimatic region, helminths in only one region were significantly more nested
      than the null model. Helminth communities were also nested across sites within
      all four bioclimatic regions. These results suggest that helminths form nested
      subsets across the archipelago due to broad-scale processes that reflect the
      overall lineages of their mammalian hosts; however, at the regional scale,
      environmental processes related to nestedness of their habitats drive parasite
      community nestedness.

PMID- 29594348
TI  - Study of a seventeenth-century French artificial mummy: autopsical, native, and
      contrast-injected CT investigations.
AB  - BACKGROUND: A lead coffin was fortuitously discovered in a church called "Eglise
      des Toussaints" in Rennes (French Brittany). A collaborative taskforce
      investigated this extraordinary discovery. A multi-disciplinary team of experts
      from the National Institute for Preventive Archeological Research (INRAP) and
      Rangueil University Hospital of Toulouse was created, including anthropologists,
      archeologists, forensic pathologists, radiologists, and pathologists. The
      inscription on the lead coffin specified that the body belonged to "Messer Louys
      de Bruslon, Lord of Plessis," a nobleman who died on November 1, 1661. Multiple
      holes were visible in the lead coffin, and deterioration threatened the mummy. We
      opened the lead coffin and discovered an excellently preserved mummy, except for
      mostly skeletonized upper and lower limbs. The mummy was conserved in several
      layers of shrouds. Vegetal embalming material covered the head and filled the
      face, the thorax, and the abdomen. The embalmers had removed all thoracic and
      abdominal organs and conserved some pelvic organs (e.g., the bladder). METHODS:
      Multi-slice computed tomography (MSCT) scanner evaluated the mummy, at each step
      of our analysis. The excellent preservation of abdominal vascular axes led us to
      perform a CT angiography using Angiofil(r), an oily contrast agent developed for
      postmortem imaging, before an autopsy. RESULTS: Sub-diaphragmatic arteries,
      including the abdominal aorta and iliac arteries, were excellently preserved. The
      vascular contrast agent filled all arteries. The native CT, CT angiography, and
      autopsy did not detect any vascular lesion. CONCLUSION: Our study, based on rare
      archeological material, allowed a complete examination of an excellently
      preserved seventeenth-century mummy, using MSCT, angiography, and an autopsy. We
      did not detect any arterial lesion and proposed a comprehensive description of
      the embalmment process.

PMID- 29594349
TI  - Clinical performance of bulk-fill and conventional resin composite restorations
      in posterior teeth: a systematic review and meta-analysis.
AB  - OBJECTIVES: The purpose of this systematic review was to compare the clinical
      performance of bulk-fill resin composites with conventional resin composites used
      for direct restorations of posterior teeth. METHODS: This review followed the
      PRISMA statement. This review was registered at PROSPERO (registration number
      CRD42016053436). A search of the scientific literature was performed by two
      independent reviewers using the PubMed/MEDLINE, Embase, The Cochrane Library, and
      Web of Science databases from commencement until January 2018. The research
      question was "Do bulk-fill resin composites have a clinical performance
      comparable to conventional resin composites in posterior restorations?" Only
      studies evaluating class I and II direct restorations in permanent teeth with a
      follow-up period of at least 1 year were included. The RevMan 5 program was used
      for meta-analysis, calculating the relative risk (RR) and 95% confidence interval
      (CI) of the dichotomous outcome (restoration failure or success). RESULTS: Ten
      articles were selected, comprising 941 analyzed restorations. The mean follow-up
      period was 33.6 months (12-72 months). No statistically significant differences
      in the failure rate were observed between conventional and base/flowable bulk
      fill resin composites (p = 0.31; RR 1.49; 95% CI 0.69-3.25) or full
      body/sculptable bulk-fill resin composites (p = 0.12; RR 1.89; 95% CI 0.84-4.24).
      CONCLUSIONS: The present systematic review and meta-analysis indicate similar
      clinical performances of bulk-fill and conventional resin composites over a
      follow-up period of 12 to 72 months. CLINICAL SIGNIFICANCE: Based on the results
      of this study, the bulk-fill resin composites could be an alternative for direct
      restorations in posterior teeth. However, clinical trials of longer duration are
      required.

PMID- 29594351
TI  - Structure of the stigma and style of Callaeum psilophyllum (Malpighiaceae) and
      its relation with potential pollinators.
AB  - The family Malpighiaceae, particularly in the Neotropic, shows a similar floral
      morphology. Although floral attraction and rewards to pollinators are alike,
      stigmas and styles show more diversity. The stigmas were described covered with a
      thin and impermeable cuticle that needs to be ruptured by the mechanical action
      of the pollinators. However, this characteristic was only mentioned for a few
      species and the anatomy and ultrastructure of the stigmas were not explored. In
      this work, we analyze the morphology, anatomy, and ultrastructure of the stigma
      and style of Callaeum psilophyllum. Moreover, we identify the potential
      pollinators in order to evaluate how the disposition of the stigmas is related
      with their size and its role in the exposure of the receptive stigmatic surface.
      Our observations indicate that Centris flavifrons, C. fuscata, C. tarsata, and C.
      trigonoides are probably efficient pollinators of C. psilophyllum. The three
      stigmas are covered by a cuticle that remained intact in bagged flowers. The
      flowers exposed to visitors show the cuticle broken, more secretion in the
      intercellular spaces between sub-stigmatic cells and abundant electron-dense
      components inside vacuoles in stigmatic papillae. This indicates that the stigmas
      prepares in similar ways to receive pollen grains, but the pollinator action is
      required to break the cuticle, and once pollen tubes start growing, stigmatic and
      sub-stigmatic cells release more secretion by a granulocrine process.

PMID- 29594350
TI  - Transcriptional Regulators as Targets for Alcohol Pharmacotherapies.
AB  - Alcohol use disorder (AUD) is a chronic relapsing brain disease that currently
      afflicts over 15 million adults in the United States. Despite its prevalence,
      there are only three FDA-approved medications for AUD treatment, all of which
      show limited efficacy. Because of their ability to alter expression of a large
      number of genes, often with great cell-type and brain-region specificity,
      transcription factors and epigenetic modifiers serve as promising new targets for
      the development of AUD treatments aimed at the neural circuitry that underlies
      chronic alcohol abuse. In this chapter, we will discuss transcriptional
      regulators that can be targeted pharmacologically and have shown some efficacy in
      attenuating alcohol consumption when targeted. Specifically, the transcription
      factors cyclic AMP-responsive element binding protein (CREB), peroxisome
      proliferator-activated receptors (PPARs), nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB), and glucocorticoid receptor (GR), as
      well as the epigenetic enzymes, the DNA methyltransferases (DNMTs) and histone
      deacetylases (HDACs), will be discussed.

PMID- 29594352
TI  - Analysis of membranous Ki-67 staining in breast cancer and surrounding breast
      epithelium.
AB  - Membranous Ki-67 staining with the MIB-1 antibody has been described in
      hyalinising trabecular adenomas of the thyroid and sclerosing haemangiomas of the
      lung. Its relatively rare occurrence in breast tumours has also been documented.
      The aim of the present study was to assess the rate of any membranous MIB-1
      staining in breast specimens. The staining was performed at room temperature with
      1:100 dilution of the antibody. One hundred four core needle biopsies and 41
      operative specimens were analysed. Membranous staining was noted in 36/144
      invasive carcinomas, 20/42 in situ carcinomas and 46/99 cases of peritumoural
      benign/normal breast epithelium. Most often, it presented as focal and partial
      polarised luminal membranous staining although complete circumferential staining
      also occurred, and membranous labelling was sometimes accompanied by cytoplasmic
      staining, too. In a few cases tested, greater dilution of the primary antibody
      did not abolish the membranous staining, which was absent with the SP6 monoclonal
      Ki-67 antibody. The membranous staining of invasive tumours showed no association
      with histological grade, lumen formation, oestrogen or progesterone receptor
      status or the Ki-67 nuclear labelling. In contrast, it was associated with a HER2
      positive status, although it occurred in all molecular subtypes approached by
      immunohistochemistry. The background of this membranous staining remains elusive.
      It is unlikely to represent an artefact. At least partial sharing of an epitope
      of the nuclear Ki-67 protein with an unidentified membranous protein and some
      functional differences between membranous staining producing tumours and tumours
      lacking this pattern of staining may both contribute to some extent.

PMID- 29594353
TI  - Immune cell expression of TGFbeta1 in cancer with lymphoid stroma: dendritic cell
      and regulatory T cell contact.
AB  - Although cancer tissue generally shows limited immune responses, some cancers
      abound with lymphocytes, which generally show favorable prognosis. These cancers,
      despite their rarity, are important in analyzing immune responses in cancer
      tissue. Transforming growth factor beta1 (TFGbeta1) is a multifunctional
      cytokine, generally having an immunosuppressive function. The present study
      analyzes the in situ TGFbeta1 expression in 23 cases of lymphocyte-rich gastric
      carcinomas (Ly-rich GCs) using immunohistochemistry and in situ hybridization.
      Immunohistochemistry revealed that latency-associated peptide (LAP) of TGFbeta1
      was localized in mainly immune cells in all cases, which was more abundant than
      in control GCs. Expression of LAP by cancer cells was only focal. In situ
      hybridization also confirmed abundant TGFbeta1 mRNA expression in the lymphoid
      stroma. Double immunofluorescent microscopy identified LAP+ cells as macrophages,
      dendritic cells, and part of T cells. Close cell-to-cell contact was observed
      between LAP+ dendritic-shaped cells and FoxP3+ regulatory T cells (Treg cells).
      Mature dendritic cells in Ly-rich GCs expressed LAP more frequently than those in
      the secondary lymphoid organs. Our data revealed abundant expression of TGFbeta1
      in immune cells with contact to Treg cells in lymphoid stroma, which is
      consistent with the notion that TGFbeta1 is one of the immunosuppressive factors
      in cancer stroma.

PMID- 29594355
TI  - High-intensity intermittent "5-10-15" running reduces body fat, and increases
      lean body mass, bone mineral density, and performance in untrained subjects.
AB  - The present study examined the effect of intense intermittent running with 5 s
      sprints on body composition, fitness level, and performance in untrained subjects
      aged 36-53 years. For 7 weeks, the subjects carried out 3 days a week 5-10-15
      training consisting of 3-9 blocks of 4 repetitions of 15, 10, and 5 s low-,
      moderate-, and high-speed running, respectively. Body fat mass was 4.3% lower (P
      < 0.01), and lean body mass and bone mineral density was 1.1 and 0.9% higher (P <
      0.01), respectively, after compared to before the intervention period (INT). The
      plasma bone turnover markers osteocalcin increased (P < 0.01) by 147%, and
      procollagen-type I N propeptide and carboxy-terminal collagen crosslinks
      increased (P < 0.05) by 84 and 76%, respectively. Furthermore, the training
      improved performance in 1500 m (P < 0.001), 3 km (P < 0.001), Yo-Yo intermittent
      endurance test (P < 0.01), and incremental treadmill running (P < 0.001) by 8.1,
      9.9, 17.2, and 23.9%, respectively. Furthermore, blood lactate after running at
      85% of maximal aerobic speed was lower (P < 0.01) after compared to before the
      INT. Thus, 7 weeks of 5-10-15 training resulted in significant health beneficial
      changes and better performance in untrained subject.

PMID- 29594354
TI  - Detection of the Merkel cell polyomavirus in the neuroendocrine component of
      combined Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the
      skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in
      80% of cases. About 5% of cases, called combined MCC, feature an admixture of
      neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or
      absence of MCPyV in combined MCC are conflicting, most favoring the absence,
      which suggests that combined MCC might have independent etiological factors and
      pathogenesis. These discrepancies might occur with the use of different virus
      identification assays, with different sensitivities. In this study, we aimed to
      determine the viral status of combined MCC by a multimodal approach. We
      histologically reviewed 128 cases of MCC and sub-classified them as "combined" or
      "conventional." Both groups were compared by clinical data (age, sex, site,
      American Joint Committee on Cancer [AJCC] stage, immunosuppression, risk of
      recurrence, and death during follow-up) and immunochemical features (cytokeratin
      20 and 7, thyroid transcription factor 1 [TTF1], p53, large T antigen [CM2B4],
      CD8 infiltrates). After a first calibration step with 12 conventional MCCs and 12
      cutaneous squamous cell carcinomas as controls, all eight cases of combined MCC
      were investigated for MCPyV viral status by combining two independent molecular
      procedures. Furthermore, on multiplex genotyping assay, the samples were examined
      for the presence of other polyoma- and papillomaviruses. Combined MCC differed
      from conventional MCC in earlier AJCC stage, increased risk of recurrence and
      death, decreased CD8 infiltrates, more frequent TTF1 positivity (5/8), abnormal
      p53 expression (8/8), and frequent lack of large T antigen expression (7/8). With
      the molecular procedure, half of the combined MCC cases were positive for MCPyV
      in the neuroendocrine component. Beta papillomaviruses were detected in 5/8
      combined MCC cases and 9/12 conventional MCC cases. In conclusion, the detection
      of MCPyV DNA in half of the combined MCC cases suggests similar routes of
      carcinogenesis for combined and conventional MCC.

PMID- 29594356
TI  - Multifunctional theranostic applications of biocompatible green-synthesized
      colloidal nanoparticles.
AB  - Phytochemicals offer immense promise for sustainable development and production
      of nanotechnology-enabled products. In the present study, Olax nana Wall. ex
      Benth. (family: Olacaceae) aqueous extract was used as an effective stabilizing
      agent to produce biogenic silver (ON-AgNPs) and gold nanoparticles (ON-AuNPs),
      which were investigated for biocompatibility and prospective biomedical
      applications (antibacterial, anticancer, antileishmanial, enzyme inhibition,
      antinociceptive, and anti-inflammatory activities). Various characterization
      techniques (XRD, FTIR, SEM, TEM, DLS, EDX, and SAED) revealed efficient
      biosynthesis of ON-AgNPs (26 nm) and ON-AuNPs (47 nm). In the toxicological
      assessment, ON-AgNPs and ON-AuNPs were found biocompatible towards human RBCs and
      macrophages (IC50 > 200 MUg/mL). In a concentration range of 62.5-2000 MUg/mL, a
      strong antibacterial effect was produced by ON-AgNPs against Staphylococcus
      epidermidis (MIC = 7.14 MUg/mL) and Escherichia coli (8.25 MUg/mL), while ON
      AuNPs was only active against Staphylococcus aureus (9.14 MUg/mL). At a
      concentration of 3.9-500 MUg/mL, a dose-dependant inhibition of HepG2 cancer
      cells was produced by ON-AgNPs (IC50 = 14.93 MUg/mL) and ON-AuNPs (2.97 MUg/mL).
      Both ON-AgNPs and ON-AuNPs were found active against Leishmania tropica (KMH23)
      promastigotes (IC50 = 12.56 and 21.52 MUg/mL) and amastigotes (17.44 and 42.20
      MUg/mL), respectively, after exposure to a concentration range of 1-200 MUg/mL
      for 72 h. Preferential enzyme inhibition against urease and carbonic anhydrase II
      were noted for ON-AgNPs (39.23 and 8.89%) and ON-AuNPs (31.34 and 6.34%),
      respectively; however, these were found inactive against xanthine oxidase at 0.2
      mg/mL. In the in vivo antinociceptive (acetic acid-induced abdominal
      constrictions) and anti-inflammatory (carrageenan-induced paw edema) activities,
      ON-AgNPs and ON-AuNPs at doses of 40 and 80 mg/kg, significantly attenuated the
      tonic nociception (P < 0.001) and ameliorated the carrageenan-induced
      inflammation (P < 0.01, P < 0.001). The results of in vitro and in vivo
      activities indicated that the biogenic nanoparticles can be used as valuable
      theranostic agents for further exploration of diverse biomedical applications.

PMID- 29594357
TI  - Insights into microbial communities mediating the bioremediation of hydrocarbon
      contaminated soil from an Alpine former military site.
AB  - The study of microbial communities involved in soil bioremediation is important
      to identify the specific microbial characteristics that determine improved
      decontamination rates. Here, we characterized bacterial, archaeal, and fungal
      communities in terms of (i) abundance (using quantitative PCR) and (ii) taxonomic
      diversity and structure (using Illumina amplicon sequencing) during the
      bioremediation of long-term hydrocarbon-contaminated soil from an Alpine former
      military site during 15 weeks comparing biostimulation (inorganic NPK
      fertilization) vs. natural attenuation and considering the effect of temperature
      (10 vs. 20  degrees C). Although a considerable amount of total petroleum
      hydrocarbon (TPH) loss could be attributed to natural attenuation, significantly
      higher TPH removal rates were obtained with NPK fertilization and at increased
      temperature, which were related to the stimulation of the activities of
      indigenous soil microorganisms. Changing structures of bacterial and fungal
      communities significantly explained shifts in TPH contents in both natural
      attenuation and biostimulation treatments at 10 and 20  degrees C. However,
      archaeal communities, in general, and changing abundances and diversities in
      bacterial and fungal communities did not play a decisive role on the
      effectiveness of soil bioremediation. Gammaproteobacteria and Bacteroidia
      classes, within bacterial community, and undescribed/novel groups, within fungal
      community, proved to be actively involved in TPH removal in natural attenuation
      and biostimulation at both temperatures.

PMID- 29594358
TI  - Production of L-valine from metabolically engineered Corynebacterium glutamicum.
AB  - L-Valine is one of the three branched-chain amino acids (valine, leucine, and
      isoleucine) essential for animal health and important in metabolism; therefore,
      it is widely added in the products of food, medicine, and feed. L-Valine is
      predominantly produced through microbial fermentation, and the production
      efficiency largely depends on the quality of microorganisms. In recent years,
      continuing efforts have been made in revealing the mechanisms and regulation of L
      valine biosynthesis in Corynebacterium glutamicum, the most utilitarian bacterium
      for amino acid production. Metabolic engineering based on the metabolic
      biosynthesis and regulation of L-valine provides an effective alternative to the
      traditional breeding for strain development. Industrially competitive L-valine
      producing C. glutamicum strains have been constructed by genetically defined
      metabolic engineering. This article reviews the global metabolic and regulatory
      networks responsible for L-valine biosynthesis, the molecular mechanisms of
      regulation, and the strategies employed in C. glutamicum strain engineering.

PMID- 29594359
TI  - [Vascular surgical training concept for military surgeons in Germany].
AB  - BACKGROUND: Due to the increasing threat of terrorist attacks and assassinations
      even in Europe, the interest in management of severe vascular injuries, which,
      with an increased incidence of 10% are to be expected with such penetrating
      wounds, is also growing; however, with increasing subspecialization in surgery
      there is a threat that the know-how in vascular surgery will become lost among
      non-vascular surgical specialists. Therefore, the Germany military established an
      educational program, the so-called DUOplus concept, to ensure that future
      military surgeons acquire and retain the experience and skills to fulfill the
      demanding role of a deployed surgeon. OBJECTIVE: The DUOplus concept of the
      German Medical Forces is introduced with a special focus on vascular surgery
      training. RESULTS: All trainee German military surgeons attain a second
      specialization alongside general surgery. This residency includes several courses
      in various surgical specialties as well as a 12-month rotation in a vascular
      surgery department. The core elements of vascular trauma training are two
      practical courses on life-like models. In these courses, which were developed
      especially for the needs of non-vascular surgeons in hands-on training, open
      surgical techniques and damage control measures including resuscitative
      endovascular balloon occlusion of the aorta (REBOA) are taught on suitable models
      and intensively practiced. CONCLUSION: All surgeons potentially confronted with
      traumatic and iatrogenic vascular injuries should have some basic competence in
      the management of vascular trauma. Especially the courses in vascular surgery for
      non-vascular surgeons offer such a skill set for every surgeon. Next to the
      German military surgeons, the courses are attended more and more by civilian and
      military surgeons from different surgical specialties and nationalities.

PMID- 29594360
TI  - A phase II, multicenter, single-arm trial of eribulin as first- or second-line
      chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation
      of efficacy, safety, and patient-reported outcomes.
AB  - PURPOSE: Although eribulin is a suitable option for early-line treatment of
      metastatic breast cancer (MBC), data on first- or second-line use of eribulin for
      human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited.
      Therefore, we conducted a phase II trial to investigate the efficacy and safety
      of eribulin for first- or second-line chemotherapy for HER2-negative MBC.
      MATERIALS AND METHODS: We performed a phase II, open-label, single-arm,
      multicenter study in Japan. Eligible patients were women with histologically
      confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line
      for MBC. The primary endpoint was the overall response rate (ORR) and the
      secondary endpoints included the clinical benefit rate (ORR + stable disease for
      6 months; CBR), progression-free survival (PFS), overall survival (OS), duration
      of response (DOR), safety, and health-related quality of life (HRQoL). RESULTS: A
      total of 35 patients with HER2-negative MBC were enrolled between March 2013 and
      February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1
      53.2%). The CBR was 54.3% (95% CI 37.8-70.8%). The median PFS was 6.2 months (95%
      CI 2.7-9.4 months) and median OS was 21.4 months (95% CI 11.5-32.9 months).
      Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia
      (2.9%). Although the majority of non-hematological adverse events were mild in
      severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared
      to maintain HRQoL of many patients. CONCLUSIONS: Eribulin as first- or second
      line chemotherapy is effective and has manageable toxicity for patients with HER2
      negative MBC.

PMID- 29594361
TI  - MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy
      through regulation of ATP7A/B.
AB  - PURPOSE: Ovarian cancer remains a most malignant female cancer nowadays. The
      acquisition of chemoresistance to common-used cisplatin-based chemotherapy
      results in a decreased overall patient survival. The present study is aimed to
      investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates
      the chemoresistance of ovarian cancer to cisplatin-based chemotherapy. METHODS:
      The expression of miR-139 in cisplatin-sensitive (n = 23) and cisplatin-resistant
      (n = 14) ovarian cancer tissues and cell lines (CAOV-3 and SNU119) was determined
      using real-time PCR assays; its effect on ovarian cancer cell chemoresistance to
      different concentrations of cisplatin was then assessed by measuring the cell
      viability using MTT assays. Next, miR-139 binding to the 3'UTR of ATP7A/B was
      confirmed using luciferase reporter gene assays. Finally, the combined effect of
      miR-139 and ATP7A/B on the chemoresistance of ovarian cancer cell was assessed.
      RESULTS: miR-139 expression was down-regulated in cisplatin-resistant ovarian
      cancer tissues (**P < 0.01) and reduced by cisplatin treatment in ovarian cell
      lines (*P < 0.05, **P < 0.01); miR-139 could enhance cisplatin-induced
      suppression on ovarian cancer cell viability, shown as reduced lC50 values; ATP7A
      and ATP7B protein levesincreased approximately 2 ~ fold-changein cisplatin
      resistant cell lines. MiR-139 directly bound to the 3'UTR of ATP7A/B,
      respectively; miR-139 inhibition increased lC50 values whereas ATP7A/B knockdown
      reduced lC50 values of CAOV-3 and SNU119 cell lines under cisplatin treatment;
      the effect of miR-139 inhibition could be partially attenuated by ATP7A/B
      knockdown. CONCLUSIONS: MiR-139/ATP7A/B axis can be a reliable biomarker for
      ovarian cancer diagnosis, and may affect the chemoresistance of ovarian cancer to
      cisplatin-based chemotherapy; rescuing miR-139 expression thus to inhibit ATP7A/B
      might contribute to dealing with the chemoresistance of ovarian cancer.

PMID- 29594362
TI  - Single-institution experience with gemcitabine-cisplatin combination therapy as a
      second-line treatment for patients with unresectable biliary tract cancer after
      failure of gemcitabine-S-1 combination therapy: a prospective feasibility study.
AB  - BACKGROUND: NCCN and Japanese clinical guidelines for the treatment of biliary
      tract cancer (BTC) addressed gemcitabine-cisplatin combination (GC) as first-line
      chemotherapy for patients with advanced BTC ineligible for surgery in 2013.
      However, gemcitabine-S1 combination therapy (GS) has been widely used as first
      line treatment in Japan because Japanese social insurance coverage of S-1 for BTC
      was approved prior to that of cisplatin. AIM: To elucidate the efficacy and
      tolerability of GC as second-line chemotherapy for patients with unresectable BTC
      after failure of GS. PATIENTS AND METHODS: Between September 2008 and August
      2011, patients with unresectable BTC who provided informed consent and received
      GC comprising gemcitabine at 1000 mg/m2 and cisplatin at 20 mg/m2 given on days 1
      and 8 in a 3-week cycle after failure of GS were included in the present study.
      Clinical data from these patients were collected prospectively. Primary endpoints
      were overall survival and time to progression (TTP). Secondary endpoints were
      response and tolerability. RESULTS: Twenty-seven patients were analyzed. Median
      survival time (MST) and TTP from the beginning of second-line treatment were 6.5
      and 3.3 months, respectively, whereas MST from the commencement of first-line
      therapy was 12.06 months. One patient showed partial response, 16 had stable
      disease and 10 experienced disease progression. As a result, disease control rate
      was 63.0%. In total, 119 courses (median, 4; range, 1-15) were administered.
      Discontinuation of GC due to drug toxicities was not observed. CONCLUSION:
      Although some issues remain to be clarified, mainly due to the small sample size,
      this single-institution experience with GC as second-line treatment after failure
      of GS showed acceptable outcomes and good tolerability.

PMID- 29594363
TI  - Electrochemical immunosensor for the breast cancer marker CA 15-3 based on the
      catalytic activity of a CuS/reduced graphene oxide nanocomposite towards the
      electrooxidation of catechol.
AB  - The authors report on an electrochemical immunosensor for the tumor marker
      carbohydrate antigen 15-3 (CA15-3). It is based on the use of a composite
      consisting of reduced graphene oxide (RGO) and copper sulfide (CuS) that was
      placed on a screen-printed graphite electrode. The electrode shows excellent
      activity towards the oxidation of catechol acting as an electrochemical probe,
      best at a working potential of 0.16 V. The electrode was modified with antibody
      against CA15-3. Once the analyte (CA15-3) binds to the surface of the electrode,
      the response to catechol is reduced. The assay has a linear response in the 1.0
      150 U mL-1 CA15-3 concentration range, with a 0.3 U mL-1 lower detection limit
      and a sensitivity of 1.88 MUA MUM-1 cm-2. The immunosensor also shows good
      reproducibility (2.7%), stability (95% of the initial values after storing for
      four weeks). The method was successfully applied to the determination of CA15-3
      in serum samples, and results were found to compare well to those obtained by an
      ELISA. Conceivably, this nanocomposite based detection scheme has a wider scope
      and may be applied to numerous other immunoassays. Graphical abstract A label
      free electrochemical immunosensor based on copper sulfides/graphene
      nanocomposites was developed for enzyme-free determination of CA15-3 biomarker.
      This immunosensor can be utilized as a tool to detect of CA15-3 in real samples.

PMID- 29594364
TI  - Recombinant rabies virus expressing interleukin-6 enhances the immune response in
      mouse brain.
AB  - Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that
      has a high mortality rate. Previous studies have indicated that recombinant RABV
      expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing
      antibodies than parental RABV in mice following intramuscular immunization. To
      investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal
      or intracranial administration in mice, the permeability of the blood-brain
      barrier (BBB), the infiltration of CD3 T cells, and innate immune response
      related effector molecules in the CNS were examined. It was observed that
      infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal
      infection. More CD3 T cells infiltrated into the central nervous system (CNS) in
      mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain.
      Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response
      related effector molecules, compared with the parental HEP-Flury strain, within
      the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger
      immune responses in mice brains, which is more beneficial for virus clearance.
      These results may also partly illustrate the role of IL6 in RABV infection.

PMID- 29594365
TI  - Microbead-based simultaneous fluorometric detection of three nut allergens.
AB  - A microbead-based method is developed for the detection of three nut allergens
      that can occur in food. The bead array constitutes of a suspension of spectrally
      distinct fluorescent polystyrene microbeads and has been applied for the
      simultaneous detection of three main and serious allergens (hazelnut, peanut and
      walnut). The method is based on the simultaneous identification of specific DNA
      sequences after PCR. The PCR products are biotinylated and hybridized to nut
      specific oligonucleotide probes attached to the microbeads. The hybrids are
      finally detected by a streptavidin-phycoerythrin conjugate and flow cytometric
      analysis. As low as 0.01% content of the three nuts in processed food (cookies)
      can be detected by this method. Graphical abstract Schematic of a method for
      simultaneous fluorometric detection of three nut allergens in processed food
      (cookies) based on the use of fluorescent microbeads and flow cytometric
      analysis. B: Biotin; SA-PE: Streptavidin conjugated to phycoerythrin.

PMID- 29594366
TI  - Metastable alpha-AgVO3 microrods as peroxidase mimetics for colorimetric
      determination of H2O2.
AB  - Single phase metastable alpha-AgVO3 microrods with high crystallinity, tetragonal
      rod-like microstructure, uniform particle size distribution, and good dispersion
      were synthesized by direct coprecipitation at room temperature. They are shown to
      be viable peroxidase mimics that catalyze the oxidation of 3,3',5,5'
      tetramethylbenzidine in the presence of H2O2. Kinetic analysis indicated typical
      Michaelis-Menten catalytic behavior. The findings were used to design a
      colorimetric assay for H2O2, best measured at 652 nm. The method has a linear
      response in the 60 to 200 MUM H2O2 concentration range, with a 2 MUM detection
      limit. Benefitting from the chemical stability of the microrods, the method is
      well reproducible. It also is easily performed and highly specific. Graphic
      abstract Single phase metastable alpha-AgVO3 microrods with high crystallinity,
      tetragonal rod-like microstructure, uniform particle size distribution, and good
      dispersion can efficiently catalyze the oxidation reaction of peroxidase
      substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to produce
      a blue color change.

PMID- 29594367
TI  - A SERS-based multiple immuno-nanoprobe for ultrasensitive detection of neomycin
      and quinolone antibiotics via a lateral flow assay.
AB  - The authors describe an ultrasensitive method for simultaneous detection of
      neomycin (NEO) and quinolones antibiotics (QNS). It is based on the use of (a)
      two immuno-nanoprobes (a probe for NEO and a probe for QNS), (b) surface-enhanced
      Raman scattering (SERS) detection, and (c), a portable lateral flow assay (LFA).
      The two probes consist of gold nanoparticles (AuNPs) conjugated to the Raman
      active molecule 4-aminothiophenol (PATP), and to monoclonal antibody against NEO
      (NEO mAb) or against NOR (NOR mAb). Quantitative detection of NEO and QNS was
      realized via SERS of the PATP-coated AuNPs captured in the test line of a LFA.
      Under optimized condition, the visual limits of LFA are 10 ng.mL-1 for NEO and
      200 ng.mL-1 for NOR, and with LODs down to 0.37 pg.mL-1 and 0.55 pg.mL-1 by using
      SERS. The NEO test line is not interfered by the NEO analogues gentamycin,
      streptomycin and tobramycin, but the NOR test line suffers from different degrees
      of cross-reactivity (CR) to 12 common other QNS, the CRs ranging from 1.5% to
      136%. The recoveries of NEO and NOR from spiked milk samples ranged between 86%
      and 121%, with relative standard deviations (RSD) from 3% to 6%. The method is
      highly sensitive, accurate and effective. It may be applied to simultaneous
      detection of NEO and 8 QNS, including NOR, enoxacin, ciprofloxacin, ofloxacin,
      fleroxacin, marbofloxacin, enrofloxacin, and pefloxacin. Graphical abstract
      Schematic of a lateral flow assay (LFA) based on an indirect competitive model.
      By using two test lines, the LFA can detect the neomycin and quinolones
      antibiotics simultaneously. Based on the surface-enhanced Raman scattering
      (SERS), the LFA shows high sensitivity to antibiotics with low limit of
      detection.

PMID- 29594368
TI  - Efficacy of individualized social competence training for children with
      oppositional defiant disorders/conduct disorders: a randomized controlled trial
      with an active control group.
AB  - Patient-focused cognitive-behavioral therapy in children with aggressive
      behavior, which uses group-based social skills training, has resulted in
      significant reductions in behavioral problems, with effect sizes in the small-to
      medium range. However, effects of individually delivered treatments and effects
      on aggressive behavior and comorbid conditions rated from different perspectives,
      child functional impairment, child quality of life, parent-child relationship,
      and parental psychopathology have rarely been assessed. In a randomized
      controlled trial, 91 boys aged 6-12 years with a diagnosis of oppositional
      defiant disorder/conduct disorder and peer-related aggression were randomized to
      receive individually delivered social competence training (Treatment Program for
      Children with Aggressive Behavior, THAV) or to an active control involving group
      play that included techniques to activate resources and the opportunity to train
      prosocial interactions in groups (PLAY). Outcome measures were rated by parents,
      teachers, or clinicians. Mostly moderate treatment effects for THAV compared to
      PLAY were found in parent ratings and/or clinician ratings on aggressive
      behavior, comorbid symptoms, psychosocial impairment, quality of life, parental
      stress, and negative expressed emotions. In teacher ratings, significant effects
      were found for ADHD symptoms and prosocial behavior only. THAV is a specifically
      effective intervention for boys aged 6-12 years with oppositional defiant
      disorder/conduct disorder and peer-related aggressive behavior as rated by
      parents and clinicians.

PMID- 29594369
TI  - Maternal adverse childhood experiences and antepartum risks: the moderating role
      of social support.
AB  - The aims of the current study were to examine the association between maternal
      adverse childhood experiences (ACEs) and antepartum health risks, and to
      investigate whether social support moderated this association. It was
      hypothesized that ACEs would be associated with antepartum health risks; however,
      social support in the prenatal period would buffer mothers from the deleterious
      consequences of ACEs. Data from 1994 women (mean age = 31 years) and their
      infants were collected from a longitudinal cohort recruited in health care
      offices in Alberta, Canada. Pregnant women completed questionnaires related to
      ACEs prior to the age of 18 and prenatal social support, and a health care
      professional assessed the mother's antepartum health risk. ACEs included
      physical, emotional, and sexual abuse, exposure to domestic violence, as well as
      exposure to household dysfunction such as parental substance use, mental illness,
      or incarceration. Regression analyses demonstrated a positive association between
      ACEs and antepartum health risks. However, a significant interaction between
      maternal ACEs and social support was also observed. Specifically, women exposed
      to high ACEs and low social support in pregnancy had high antepartum health
      risks. However, among mothers who had high ACEs but also high levels of social
      support, there was no association between ACEs and antepartum health risk. A
      history of ACEs can place mothers at risk of antepartum health complications.
      However, a resiliency effect was observed: women with a history of ACEs were
      buffered from experiencing antepartum health risks if they reported high levels
      of social support in pregnancy.

PMID- 29594370
TI  - Gender difference in the point prevalence, symptoms, comorbidity, and correlates
      of depression: findings from the Lagos State Mental Health Survey (LSMHS),
      Nigeria.
AB  - It is still unclear whether the gender difference in the rate of depression cuts
      across cultures or is specific to some depressive symptoms. This study evaluated
      the gender difference in current prevalence, symptoms, comorbidity, and
      correlates of depression in Lagos, Nigeria. A total of 11,246 adult participants
      (6525 females and 4712 males) in a face-to-face household survey were assessed
      for symptoms of depression. They were also assessed for symptoms of anxiety,
      somatic symptoms, alcohol and substance use disorders, and disability. The
      difference between the point prevalence for symptoms of depression in females
      (6.3%, s.e 0.3) and males (4.4%, s.e 0.3) was significant (OR 1.28, 95% CI 1.14
      1.59). Compared to males, females had significantly higher rates for anhedonia
      (OR 1.20), hypersomnia (OR 2.15), fatigue (OR 1.49), guilt/worthless feeling (OR
      1.41), poor concentration (OR 1.32), psychomotor retardation (OR 1.51), and
      suicidal ideation (OR 1.32). However, poor appetite (OR 0.69) and comorbidity
      with alcohol use (OR 0.25) was significantly lower in females compared to males.
      The significantly higher rates for depression in females were only restricted to
      below 45 years and higher socioeconomic status. Our study further contributed to
      the growing literature suggesting that the gender differences in rates of
      depression not only cut across many cultures, but most pronounced with atypical
      symptoms, not affected by recall bias and seems to disappear with increasing age.
      These need to be considered when formulating mental health policies for equitable
      and acceptable health services.

PMID- 29594371
TI  - B cell depletion reduces T cell activation in pancreatic islets in a murine
      autoimmune diabetes model.
AB  - AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease
      characterised by the destruction of beta cells in the islets of Langerhans,
      resulting in deficient insulin production. B cell depletion therapy has proved
      successful in preventing diabetes and restoring euglycaemia in animal models of
      diabetes, as well as in preserving beta cell function in clinical trials in the
      short term. We aimed to report a full characterisation of B cell kinetics post B
      cell depletion, with a focus on pancreatic islets. METHODS: Transgenic NOD mice
      with a human CD20 transgene expressed on B cells were injected with an anti-CD20
      depleting antibody. B cells were analysed using multivariable flow cytometry.
      RESULTS: There was a 10 week delay in the onset of diabetes when comparing
      control and experimental groups, although the final difference in the diabetes
      incidence, following prolonged observation, was not statistically significant (p
      = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation
      of B cells during B cell depletion and repopulation. IL-10-producing regulatory B
      cells were not induced in repopulated B cells in the periphery, post anti-CD20
      depletion. However, the early depletion of B cells had a marked effect on T cells
      in the local islet infiltrate. We demonstrated a lack of T cell activation,
      specifically with reduced CD44 expression and effector function, including IFN
      gamma production from both CD4+ and CD8+ T cells. These CD8+ T cells remained
      altered in the pancreatic islets long after B cell depletion and repopulation.
      CONCLUSIONS/INTERPRETATION: Our findings suggest that B cell depletion can have
      an impact on T cell regulation, inducing a durable effect that is present long
      after repopulation. We suggest that this local effect of reducing autoimmune T
      cell activity contributes to delay in the onset of autoimmune diabetes.

PMID- 29594373
TI  - Comparison of Dimeglio and Pirani score in predicting number of casts and need
      for tenotomy in clubfoot correction using the Ponseti method.
AB  - PURPOSE: The Dimeglio and the Pirani scores are largely used to rate clubfoot at
      presentation and monitor correction. To date, the accuracy of these scores in
      predicting appropriate treatment is controversial. The aim of this study was to
      investigate the accuracy of Dimeglio and Pirani scores in predicting the number
      of casts and the need for tenotomy in clubfoot correction using the Ponseti
      method. METHODS: Ninety-one consecutive feet (54 patients; mean age at
      presentation: 28 +/- 15 days) undergoing clubfoot correction using the Ponseti
      method were prospectively followed from first casting to correction. All feet
      were scored according to the Dimeglio and Pirani score. The relationships between
      the two scores, the number of casts and the need for tenotomy were analysed.
      RESULTS: Initial correction was achieved in all feet. Both Dimeglio (r = .73; p
      value < .0005) and Pirani scores (r = .56; p value < .000) showed good
      association with the number of casts. Multiple linear regression showed a high
      collinearity of the two scores but a more significant contribution of the
      Dimeglio score. Among subcomponents, hindfoot score, midfoot score, varus and
      muscular abnormality were independent predictors of the number of casts. Both
      Dimeglio and Pirani scores were significantly associated with the need for
      tenotomy (p value = .0000), and odds ratios and cut-off points were calculated.
      The receiving operator curve (ROC) analysis showed slightly better performance of
      the Dimeglio in comparison with the Pirani score in predicting the need for
      tenotomy, but the difference between the two areas under the curve (AUC) was not
      significant (p = .48). CONCLUSIONS: A quite accurate prediction of the number of
      casts and the need for tenotomy can be performed in most cases. The Dimeglio
      score showed slightly better accuracy in predicting both steps of Ponseti
      treatment.

PMID- 29594372
TI  - Short-term outcomes of heart failure patients with reduced and preserved ejection
      fraction after acute decompensation according to the final destination after
      emergency department care.
AB  - AIMS: To compare short-term outcomes after an episode of acute heart failure
      (AHF) in patients with reduced and preserved ejection fractions (HFrEF, < 40%;
      and HFpEF, > 49%; respectively) according to their destinations after emergency
      department (ED) care. METHODS AND RESULTS: This secondary analysis of the EAHFE
      Registry (consecutive AHF patients diagnosed in 41 Spanish EDs) investigated 30
      day all-cause mortality, in-hospital all-cause mortality, prolonged
      hospitalisation (> 7 days), and 30-day post-discharge ED revisit due to AHF, all
      cause death, and combined endpoint (ED revisit/death) in 5829 patients with
      echocardiographically documented HFrEF and HfpEF (HFrEF/HFpEF: 1,442/4,387).
      Adjusted ratios were calculated for patients admitted to internal medicine (IM),
      short stay unit (SSU), and discharged from the ED without hospitalisation (DEDWH)
      and compared with those admitted to cardiology. For HFrEF, the only significant
      differences were lower in-hospital mortality (OR = 0.26; 95% CI 0.08-0.81; p =
      0.021) and prolonged hospitalisation (OR = 0.07; 95% CI 0.04-0.13; p < 0.001)
      related to SSU admission. For HFpEF, IM admission had a higher post-discharge 30
      day mortality (HR = 1.85; 95% CI 1.05-3.25; p = 0.033) and combined endpoint (HR
      = 1.24; 95% CI 1.01-1.64; p = 0.044); SSU admission had a lower in-hospital
      mortality (OR = 0.43; 95% CI 0.23-0.80; p = 0.008) and prolonged hospitalisation
      (OR = 0.17; 95% CI 0.13-0.23; p < 0.001) but a higher post-discharge 30-day
      combined endpoint (HR = 1.29; 95% CI 1.01-1.64; p = 0.041); and DEDDWH had a
      lower 30-day mortality (HR = 0.46; 95% CI 0.28-0.75; p = 0.002) but higher post
      discharge ED revisit (HR = 1.62; 95% CI 1.31-2.00; p < 0.001). CONCLUSION: While
      HFrEF patients have similar short-term outcomes irrespective of the destination
      after ED care for an AHF episode, HFpEF patients present worse short-term
      outcomes when managed by non-cardiology departments, despite adjustment for
      different clinical patient profiles. Reasons for this heterogeneous specialty
      related performance should be investigated.

PMID- 29594374
TI  - [Pulmonary hypertension in connective tissue disease].
AB  - Pulmonary arterial hypertension (PAH) is a major complication of systemic
      sclerosis (SSc) and screening is recommended for a timely initiation of disease
      targeted drug therapy to modify disease progression. Patients with SSc-PAH have a
      better prognosis when detected and treated early. The PAH can occur in all
      disease stages and subsets of SSc. Regular screening tests, which are indicative
      for PAH, e.g. echocardiography, diffusion capacity, brain natriuretic protein
      (BNP) and a 6-min walking test, are recommended to enhance the suspicion, since
      clinical symptoms are unspecific and occur late in the course of PAH. In patients
      with suspected PAH, the diagnosis should be confirmed by right heart
      catheterization. A multidisciplinary approach in expert centres including
      rheumatologists and respiratory physicians and cardiologists specialized in
      pulmonary hypertension is mandatory for management of patients with SSc at risk
      for or with manifest pulmonary arterial hypertension.

PMID- 29594375
TI  - Amperometric myeloperoxidase immunoassay based on the use of CuPdPt nanowire
      networks.
AB  - This research describes a nanowire network-based method for detecting the
      activity of myeloperoxidase (MPO), a biomarker of acute coronary syndromes (ACS).
      Trimetallic CuPdPt nanowire networks (CuPdPt NWNWs) were prepared by a one-step
      chemical reduction method. The metallic precursors quickly form nanowire network
      structures without the need for additional capping agents or surfactants. This
      process creates a product with a clean surface. The NWNWs were dropped onto a
      glassy carbon electrode (GCE) to obtain a sensor with good catalytic activity
      towards the reduction of hydrogen peroxide (H2O2), which was used as an
      electrochemical probe working at -0.4 V (vs. SCE). It also provided a large
      surface for further modification. Next, an antibody against MPO was immobilized
      on the modified GCE via the stable conjunction between Cu, Pt, Pd and amino
      groups. Upon binding of MPO to the antibody on the GCE, the current response to
      H2O2 was reduced by 35 MUA.cm-2. The immunosensor had a linear response within
      the 100 fg.mL-1 to 50 ng.mL-1 MPO concentration range and a 33 fg.mL-1 detection
      limit (at an S/N ratio of 3). The recovery of spiked serum samples ranged from
      99.8 to 103.6%. This result suggests that the method can be applied to the
      quantitation of MPO in human serum samples. Graphical abstract A trimetallic
      CuPdPt nanowire networks was placed on a glassy cabon electrode (GCE) to design
      an immunosensor for myeloperoxidase (MPO), a biomarker for the acute coronary
      syndrome (ACS). Antibody against MPO was immobilized on the network via
      conjugation between Cu, Pt, Pd and amino groups. Amperometric i-t measurements
      were conducted to quantify the amount of MPO that binds to the antibody on the
      surface of the modified GCE.

PMID- 29594376
TI  - Loop-mediated isothermal amplification for visual detection of Vibrio
      parahaemolyticus using gold nanoparticles.
AB  - Loop-mediated isothermal amplification (LAMP) eradicates the need of thermocycler
      in DNA amplification. Signals are usually obtained via fluorometry or
      turbidimetry, but such methods need improvement in order to become more
      effortless and reliable. The authors describe a set of six specific primers
      targeting the species-specific tlh gene of Vibrio parahaemolyticus which were
      used in accelerated LAMP reaction. Gold nanoparticles (AuNPs) were functionalized
      with streptavidin (Avidin-AuNPs), and engineered to signal the LAMP reaction. Two
      of the loop primers for LAMP were biotinylated and then can produce a DNA that
      can cause clusterization of Avidin-AuNPs based on the formation of avidin-biotin
      complex. This leads to a color change of the solution from red to blue.
      Amplification is completed within 30 min and can be visually detected within 5
      min. The detection limit of the method is found to be 8.6 cfu per reaction. This
      visual detection scheme does not require any fluorescent reagents and detection
      instruments. Conceivably, the method has a wide scope because such Avidin-AuNPs
      can be used as nanoprobes for a variety of other LAMP products. This rapid and
      universal strategy holds promise in point of care testing and food testing,
      particularly in resource-limited regions. Graphical abstract Six specific primers
      (two of them are biotinylated) were used to realize the accelerated Loop-Mediated
      Isothermal Amplification. Streptavidin modified gold nanoparticles (Avidin-AuNPs)
      cluster on the DNA products, leading to the apparent change of color from red to
      blue, which is readily identified even by unaided eye.

PMID- 29594377
TI  - A gold electrode modified with a nanoparticulate film composed of a conducting
      copolymer for ultrasensitive voltammetric sensing of hydrogen peroxide.
AB  - A film consisting of poly(gamma-glutamic acid) modified with 3-aminothiophene
      (ATh-gamma-PGA) was prepared by macromolecular self-assembly and
      electropolymerization. ATh-gamma-PGA is amphiphilic and electrically conductive.
      The copolymers undergo self-assembly to form nanoparticles (NPs) on decreasing
      the pH value of an aqueous solution. A conducting film of NPs was formed on the
      surface of a gold electrode by casting the ATh-gamma-PGA NPs and subsequently
      electropolymerizing the thiophene units. Next, horseradish peroxidase and Nafion
      were cast onto the film to obtain an enzymatic biosensor for H2O2. Due to the
      electropolymerization step, a cross-conjugated polymer network is created that
      improves electron transfer rates and thus enhances the response. This endows the
      biosensor with high sensitivity. Two linear ranges are present, the first ranging
      from 1 * 10-11 to 1 * 10-8 mol.L-1, and the second from 1 * 10-8 to 1 * 10-5
      mol.L-1. The detection limit is as low as 3 * 10-12 mol.L-1. The sensor is
      stable, repeatable, and was successfully applied to the determination of H2O2 in
      a commercial disinfecting solution. Graphical abstract Preparation of a
      conducting nanoparticle (NP) film on the gold electrode (GE) by self-assembly of
      poly(gamma-glutamic acid) that was modified with electroactive 3-aminothiophene
      (ATh-gamma-PGA). It served as a platform for the fabricationof an ultrasensitive
      voltammetric enzyme-based biosensor for H2O2.

PMID- 29594378
TI  - Chemiluminescence assay for detection of 2-hydroxyfluorene using the G-quadruplex
      DNAzyme-H2O2-luminol system.
AB  - A chemiluminescence (CL) based assay is described for the determination of the
      environmental pollutant 2-hydroxyfluorene (2-HOFlu) which is found to inhibit the
      CL of a system composed of the G-quadruplex/hemin complex (a DNAzyme), H2O2, and
      luminol. The G-rich aptamer PW17 is transformed to a potassium(I)-stabilized G
      quadruplex-hemin complex which displays peroxidase-like activity to catalyze the
      oxidation of luminol by H2O2 which is accompanied by strong blue CL emission. On
      addition of 2-HOFlu, it will participate in the G-quadruplex DNAzyme-mediated
      oxidation by H2O2. As a result, CL intensity is decreased. The difference in CL
      intensity (DeltaI) before and after addition of 2-HOFlu serves as the signal for
      its quantitation. In water of pH 9.0, a linear relationship is found for the 1 nM
      to 1 MUM concentration range, with a 0.2 nM detection limit. The assay is highly
      selective over other fluorene derivatives. It was successfully applied to the
      determination of 2-HOFlu in spiked lake water samples. The method is rapid, cost
      effective and convenient. Conceivably, it has a wide scope in that it may be
      applied to other target pollutants for which G-quadruplexes are available.
      Graphical abstract A chemiluminescence (CL) assay is described for the
      determination of the environmental pollutant 2-hydroxyfluorene (2-HOFlu) based on
      the inhibition of the CL system composed of the G-quadruplex/hemin complex (a
      DNAzyme), H2O2, and luminol.

PMID- 29594379
TI  - An oligosorbent-based aptamer affinity column for selective extraction of
      aflatoxin B2 prior to HPLC with fluorometric detection.
AB  - The article describes an aptamer affinity column for selective solid-phase
      extraction of aflatoxin B2 (AFB2). Amino-modified aptamer against AFB2 was
      immobilized on CNBr-activated Sepharose through a covalent bond. The effects of
      oligosorbents based on 3'- or 5'-amino-modified sequences with a C6 or a C7
      spacer arm were evaluated by UV spectroscopy at 260 nm. The extraction recovery
      was evaluated by HPLC with fluorometric detection. The extraction of AFB2 was
      optimized. Under the optimum conditions, the aptamer affinity column has a linear
      response to AFB2 in the range of 0.5-80 ng, with a capacity of 84.6 ng. Control
      supports without immobilized aptamers and a nonspecific oligosorbent immobilized
      with a negative control oligonucleotide were studied in order to demonstrate
      selectivity. The method was tested with spiked peanut sample (0.5-50 MUg.kg-1
      AFB2) and gave average recoveries of 80.9% and a mean relative standard deviation
      of 1.9%. The limit of detection is 25 pg.mL-1. This is much lower than the
      maximum residue limits suggested by the European Union. The columns can be re
      used up to five times without any loss of performance. The oligosorbent was also
      applied to clean-up of AFB2 from peanut sample extracts before HPLC analysis.
      Results were further confirmed by ultra-fast liquid chromatography with tandem
      mass spectrometry. Conceivably, the method may also be applied to other samples,
      such as food, agricultural products, and traditional Chinese medicines. Graphical
      abstract Schematic illustration of the fabrication procedures of aptamer affinity
      column, AAC (a), its principle of aptamer bound to aflatoxin B2 (b) and the
      obtained AAC

PMID- 29594380
TI  - An Attempt to Find a Suitable Biomass for Biochar-Based Polypropylene
      Biocomposites.
AB  - Four biomass wastes (rice husk, coffee husk, coarse wool, and landfill wood) were
      added with biochar and polypropylene (PP) to manufacture biocomposites.
      Individual biomasses were tested for their combustion behavior using cone
      calorimeter. Biocomposites were analyzed for their fire/thermal, mechanical, and
      morphological properties. Wood had the most desirable comprehensive effect on
      both the mechanical and fire properties of composites. In particular, wood and
      biochar composite exhibited the highest values of tensile/flexural properties
      with a relatively low peak heat release rate. In general, application of waste
      derived biochar and biomasses drastically reduced the susceptibility of neat PP
      towards fire.

PMID- 29594381
TI  - Magnetic nanoparticles coated with poly(p-phenylenediamine-co-thiophene) as a
      sorbent for preconcentration of organophosphorus pesticides.
AB  - The authors describe the preparation of Fe3O4 nanoparticles coated with poly(p
      phenylenediamine-co-thiophene). The resulting nanoparticles (NPs) are shown to be
      viable sorbents for use in magnetic solid-phase extraction (MSPE) of
      organophosphorus pesticides (OPPs). The coated NPs were characterized by BET,
      FTIR, scanning electron microscopy and transmission electron microscopy.
      Following sorption of OPPs and subsequent desorption with dichloromethane, the
      OPPs were quantified by GC in combination with FID. Under optimal conditions, the
      preconcentration factors range from 118 to 163. Other figures of merit include
      (a) a linear response between 0.3 and 500 ng mL-1; (b) detection limits (at an
      S/N ratio of 3) between 0.1 and 0.3 ng mL-1, and (c) a precision (for n = 5)
      between 4.7 and 8.1% at concentration levels of 1, 10 and 100 ng mL-1). The
      nanocomposites can be reused up to 8 times. The method was applied to the
      analysis of spiked environmental water samples and fruit juices and gave relative
      recoveries in the range of 88.1 to 99.2%. Graphical abstract Schematic
      presentation of the synthesis of core-shell magnetic nanoparticles (MNPs) of the
      type poly(pPDA-co-Th)@Fe3O4, and their application as a sorbent for magnetic
      solid-phase extraction (MSPE) of organophosphorus pesticides.

PMID- 29594382
TI  - Ratiometric ultrasensitive fluorometric detection of ascorbic acid using a dually
      emitting CdSe@SiO2@CdTe quantum dot hybrid.
AB  - A dually emitting quantum dot nanohybrid was designed for the fluorometric 2
      wavelength determination of ascorbic acid (AA). The nanohybrid consists of red
      emitting CdTe quantum dots (QDs) covalently linked to the surface of silica
      nanoparticles containing green-emitting CdSe QDs. The fluorescence of the red
      emitting CdTe QDs (peaking at 616 nm) is first quenched by addition of KMnO4 due
      to oxidation under formation of CdTeO3 and TeO2. On addition of AA, the red
      fluorescence is restored due to the reduction of surface CdTeO3/TeO2 to form
      CdTe. The green fluorescence of the green-emitting CdSe QDs (peaking at 522 nm),
      in contrast, remains constant and its intensity serves as a reference signal.
      Both kinds of QDs can be photoexcited at 380 nm. An easily distinguishable
      transition in fluorescence (from green to orange-red) can be observed on
      increasing the amount of added AA. Under optimal conditions, the ratio of the
      intensities of the red and the green fluorescence increases linearly in the 0.1
      to 5.0 MUM AA concentration range, and the detection limit is as low as 35 nM.
      The assay was successfully applied to the quantitation of AA in (spiked) fruit
      juice samples. Graphical abstract A new dually emitting CdSe@SiO2@CdTe nanohybrid
      was designed for ratiometric ultrasensitive fluorometric detection of ascorbic
      acid in fruit juice samples.

PMID- 29594383
TI  - Highly sensitive electrochemical DNA sensor based on the use of three-dimensional
      nitrogen-doped graphene.
AB  - This paper describes a voltammetric method for sensitive determination of
      specific sequences of DNA. The assay is based on three-dimensional nitrogen-doped
      graphene (3D-NG) which, due to its excellent electrical conductivity, provides a
      favorable microenvironment to retain the activity of immobilized probe single
      stranded DNA and also facilitates electron transfer. The free-standing 3D-NG
      electrode was characterized by scanning electron microscopy, Raman and X-ray
      photoelectron spectroscopy, cyclic voltammetry, and electrochemical impedance
      spectroscopy. Differential pulse voltammetry was applied to monitor DNA
      hybridization using Methylene Blue as an electrochemical indicator. Under optimal
      conditions, the peak currents (best measured at 0.28 V vs. Ag/AgCl) increase
      linearly with the logarithm of the concentrations of ssDNA in the 10 f. to 10 nM
      concentrations range, with a 3.5 f. detection limit (at a signal/noise ratio of
      3). The biosensor exhibits good selectivity for ssDNA and can distinguish even
      single-base mismatches. The capability of the method was tested with spiked serum
      samples, and excellent reproducibility and stability is found. This indicates
      that the strategy is promising for use in clinical applications. Graphical
      abstract Three-dimensional nitrogen-doped graphene as an innovative and simple
      electrochemical DNA biosensor was fabricated and used in a biosensor that shows
      high sensitivity and good performance in the determination of target DNA in human
      serum samples.

PMID- 29594384
TI  - Femicide trends in Brazil: relationship between public interest and mortality
      rates.
AB  - In this information epidemiology (infodemiology) study, we describe the online
      public interest about the issue of femicide in Brazil and analyze the
      relationship between search queries and femicide trends from 2004 to 2015. We
      showed that information-seeking behavior for femicide in the Brazilian states has
      been strongly influenced by female homicide rates. Educational and policy-related
      interventions are needed to improve the population's knowledge and attitude
      toward femicide.

PMID- 29594385
TI  - Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.
AB  - INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL
      1/Cryptic family. Besides being critical for early embryonic development, Cripto
      1 is also associated with the development and behavior of several cancers.
      OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands
      (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas
      (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs
      underwent immunohistochemical study by the polymeric biotin-free technique.
      Immunopositive cells were evaluated semiquantitatively (scores 0-3). For
      statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a
      significance level of p <= 0.05 was established. RESULTS: Most CaExPAs (n = 10)
      were strong positive (score 3) for Cripto-1, and only three cases of PAs and two
      specimens of NSGs exhibited some expression (score 1), being statistically
      significant these findings (p < 0.001). No difference between the expression of
      this protein in tumors of major and minor salivary glands was observed.
      Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8)
      when compared to those without capsular invasion (intracapsular pattern) (p =
      0.036). Patients with or without lymph node metastasis showed no difference (p =
      0.294). CONCLUSION: The results revealed a significantly higher expression of
      Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly
      deregulated in PA malignant transformation. Furthermore, the increased expression
      of this protein is associated with a more aggressive behavior (invasive growth)
      in salivary gland tumors.

PMID- 29594386
TI  - Mutational analysis uncovers monogenic bone disorders in women with pregnancy
      associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2.
AB  - : Pregnancy was found to be a skeletal risk factor promoting the initial onset of
      previously unrecognized monogenic bone disorders, thus explaining a proportion of
      cases with pregnancy-associated osteoporosis. Therapeutic measures should focus
      in particular on the normalization of the disturbed calcium homeostasis in order
      to enable the partial skeletal recovery. INTRODUCTION: Pregnancy-associated
      osteoporosis (PAO) is a rare skeletal condition, which is characterized by a
      reduction in bone mineral density (BMD) in the course of pregnancy and lactation.
      Typical symptoms include vertebral compression fractures and transient
      osteoporosis of the hip. Since the etiology is not well understood, this
      prospective study was conducted in order to elucidate the relevance of pathogenic
      gene variants for the development of PAO. METHODS: Seven consecutive cases with
      the diagnosis of PAO underwent a skeletal assessment (blood tests, DXA, HR-pQCT)
      and a comprehensive genetic analysis using a custom-designed gene panel. RESULTS:
      All cases showed a reduced BMD (DXA T-score, lumbar spine - 3.2 +/- 1.0; left
      femur - 2.2 +/- 0.5; right femur - 1.9 +/- 0.5), while the spine was affected
      more severely (p < 0.05). The trabecular and cortical thickness was overall
      reduced in HR-pQCT, while the trabecular number showed no alterations in most
      cases. The genetic analysis revealed three novel mutations in LRP5, COL1A1, and
      COL1A2. CONCLUSION: Our data show that previously unrecognized monogenic bone
      disorders play an important role in PAO. Pregnancy should be considered a
      skeletal risk factor, which can promote the initial clinical onset of such
      skeletal disorders. The underlying increased calcium demand is essential in terms
      of prophylactic and therapeutic measures, which are especially required in
      individuals with a genetically determined low bone mass. The implementation of
      this knowledge in clinical practice can enable the partial recovery of the
      skeleton. Consistent genetic studies are needed to analyze the frequency of
      pathogenic variants in women with PAO.

PMID- 29594388
TI  - The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and
      a potential competitor of the 19S.
AB  - The interaction of insulin-degrading enzyme (IDE) with the main intracellular
      proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity,
      mass spectrometry and native gel electrophoresis. IDE was mainly detected in
      association with assemblies with at least one free 20S end and biochemical
      investigations suggest that IDE competes with the 19S in vitro. IDE directly
      binds the 20S and affects its proteolytic activities in a bimodal fashion, very
      similar in human and yeast 20S, inhibiting at (IDE) <= 30 nM and activating at
      (IDE) >= 30 nM. Only an activating effect is observed in a yeast mutant locked in
      the "open" conformation (i.e., the alpha-3DeltaN 20S), envisaging a possible role
      of IDE as modulator of the 20S "open"-"closed" allosteric equilibrium. Protein
      protein docking in silico proposes that the interaction between IDE and the 20S
      could involve the C-term helix of the 20S alpha-3 subunit which regulates the
      gate opening of the 20S.

PMID- 29594387
TI  - Redox-dependent thiol modifications: implications for the release of
      extracellular vesicles.
AB  - Extracellular vesicles (EVs), including microvesicles and exosomes, are emerging
      as important regulators of homeostasis and pathophysiology. During pro
      inflammatory and pro-oxidant conditions, EV release is induced. As EVs released
      under such conditions often exert pro-inflammatory and procoagulant effects, they
      may actively promote the pathogenesis of chronic diseases. There is evidence that
      thiol group-containing antioxidants can prevent EV induction by pro-inflammatory
      and oxidative stimuli, likely by protecting protein thiols of the EV-secreting
      cells from oxidation. As the redox state of protein thiols greatly impacts three
      dimensional protein structure and, consequently, function, redox modifications of
      protein thiols may directly modulate EV release in response to changes in the
      cell's redox environment. In this review article, we discuss targets of redox
      dependent thiol modifications that are known or expected to be involved in the
      regulation of EV release, namely redox-sensitive calcium channels, N
      ethylmaleimide sensitive factor, protein disulfide isomerase, phospholipid
      flippases, actin filaments, calpains and cell surface-exposed thiols. Thiol
      protection is proposed as a strategy for preventing detrimental changes in EV
      signaling in response to inflammation and oxidative stress. Identification of the
      thiol-containing proteins that modulate EV release in pro-oxidant environments
      could provide a rationale for broad application of thiol group-containing
      antioxidants in chronic inflammatory diseases.

PMID- 29594389
TI  - Follistatin-like 1 in development and human diseases.
AB  - Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression
      changes during development and disease, among which cardiovascular disease,
      cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively
      studied over the last years, though its mechanism of action remains elusive.
      FSTL1 is involved in multiple signaling pathways and biological processes,
      including vascularization and regulation of the immune response, a feature that
      complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been
      shown, but other molecular partners probably exist. During cancer progression and
      rheumatoid arthritis, controversial data have been reported with respect to the
      proliferative, apoptotic, migratory, and inflammatory effects of FSTL1. This
      controversy might reside in the extensive post-transcriptional regulation of
      FSTL1. The FSTL1 primary transcript also encodes for a microRNA (miR-198) in
      primates and multiple microRNA-binding sites are present in the 3'UTR. The switch
      between expression of the FSTL1 protein and miR-198 is an important regulator of
      tumour metastasis and wound healing. The glycosylation state of FSTL1 is a
      determinant of biological activity, in cardiomyocytes the glycosylated form
      promoting proliferation and the non-glycosylated working anti-apoptotic.
      Moreover, the glycosylation state shows differences between species and tissues
      which might underlie the differences observed in in vitro studies. Finally,
      regulation at the level of protein secretion has been described.

PMID- 29594390
TI  - Voltammetric sensing based on the use of advanced carbonaceous nanomaterials: a
      review.
AB  - This review (with 210 references) summarizes recent developments in the design of
      voltammetric chemical sensors and biosensors based on the use of carbon
      nanomaterials (CNMs). It is divided into subsections starting with an
      introduction into the field and a description of its current state. This is
      followed by a large section on various types of voltammetric sensors and
      biosensors using CNMs with subsections on sensors based on the use of carbon
      nanotubes, graphene, graphene oxides, graphene nanoribbons, fullerenes, ionic
      liquid composites with CNMs, carbon nanohorns, diamond nanoparticles, carbon
      dots, carbon nanofibers and mesoporous carbon. The third section gives conclusion
      and an outlook. Tables are presented on the application of such sensors to
      voltammetric detection of neurotransmitters, metabolites, dietary minerals,
      proteins, heavy metals, gaseous molecules, pharmaceuticals, environmental
      pollutants, food, beverages, cosmetics, commercial goods and drugs of abuse. The
      authors also describe advanced approaches for the fabrication of robust
      functional carbon nano(bio)sensors for voltammetric quantification of multiple
      targets. Graphical Abstract Featuring execellent electrical, catalytic and
      surface properies, CNMs have gained enormous attention for designing voltammetric
      sensors and biosensors. Functionalized CNM-modified electrode interfaces have
      demonstrated their prominent role in biological, environmental, pharmaceutical,
      chemical, food and industrial analysis.

PMID- 29594391
TI  - Aptamer-modified carbon nanomaterial based sorption coupled to paper spray ion
      mobility spectrometry for highly sensitive and selective determination of
      methamphetamine.
AB  - A cellulose paper was modified with an aptamer against methamphetamine on either
      carbon dots (CDs) or on multichannel carbon nanotubes (CNTs). The resulting
      sorbent was applied to the extraction of METH from blood or saliva. The METH
      loaded paper than also was directly applied as a paper spray ionization source in
      ion mobility spectrometry. The carbon nanomaterial enhances sensitivity, and the
      aptamer enhances selectivity. The materials were covalently bound to the paper on
      one side, while the aptamer was immobilized on the other. After optimization of
      the extraction process and instrumental parameters, the limits of detection when
      using the aptamer-CNT modified paper are 0.6 ng.mL-1 for saliva, and 0.45 ng.mL-1
      for plasma. The respective values when using aptamer-CD modified paper are 1.5
      ng.mL-1 for saliva and 0.9 ng.mL-1 for plasma. Calibration plots are linear in
      the 2 to 150 ng.mL-1 METH concentration range for saliva, and in the 1.5 to 200
      ng.mL-1 concentration ranges for blood when using the aptamer-CNT based method.
      When using the aptamer-CDs, the dynamic ranges extend from 5 to 200 ng.mL-1 and
      from 3 to 250 ng.mL-1, respectively. The method was applied to the determination
      of METH in real samples of saliva and blood, and the accuracy of the method was
      confirmed by comparison of the results with data analyzed by GC-MS. Graphical
      abstract ?.

PMID- 29594392
TI  - A nanocomposite consisting of poly(methyl methacrylate), graphene oxide and Fe3O4
      nanoparticles as a sorbent for magnetic solid-phase extraction of aromatic
      amines.
AB  - Graphene oxide (GO) was conjugated to magnetite nanoparticles and then coated
      with poly(methyl methacrylate) to obtain a nanomaterial of the type PMMA@GO
      Fe3O4, which is shown to be a viable sorbent for magnetic solid-phase extraction.
      The nanocomposite was characterized by SEM, TEM, XRD, VSM and FTIR spectroscopy.
      It was applied to the extraction of the aromatic amines aniline, N,N
      dimethylaniline, o-toluidine, and 3-chloroaniline. Under optimal conditions, the
      preconcentration factors range from 139 to 173. Following desorption with
      dichloromethane, the amines were quantified by GC. Analytical figures of merit
      include (a) a linear range extending from 0.007-100 ng mL-1, (b) detection limits
      between 2 and 6 pg mL-1; and (c) relative standard deviations between 5.9 and
      8.6% (for n = 5; at 0.05, 5.0 and 50 ng mL-1 levels, respectively). The method
      was successfully applied to the determination of aromatic amines in spiked real
      water samples and gave recoveries in the range of 90.3%-99.0%. Graphical abstract
      A magnetic sorbent was fabricated by deposition of poly(methyl methacrylate) onto
      Fe3O4-magnetized graphene oxide. It was applied to the extraction and
      preconcentration of aromatic amines from water samples prior to their gas
      chromatography-flame ionization detector (GC-FID) determination.

PMID- 29594393
TI  - Fluorometric aptamer assay for ochratoxin A based on the use of single walled
      carbon nanohorns and exonuclease III-aided amplification.
AB  - The authors describe an aptamer based assay for the food mycotoxin ochratoxin A
      (OTA). It is based on the use of exonuclease III (Exo III) which assists in
      signal amplification, and of single-walled carbon nanohorns (SWCNHs) which act as
      quenchers of fluorescence. The detection scheme employs a hairpin probe (HP) and
      a signal probe (SP) labeled with carboxyfluorescein (FAM) at its 5'-end. The
      fluorescence of intact SPs (best measured at excitation/emission wavelengths of
      495/518 nm) is quenched by SWCNHs. The HP contains the OTA-specific aptamer
      sequence and is partially complementary to the SP. After addition of OTA, the
      aptamer binds OTA and thus exposes a single-stranded sequence that can hybridize
      with the SP. Exo III digests the SP to liberate the free fluorophore labels. The
      damaged SPs no longer are adsorbed by the SWCNHs so that fluorescence is no
      longer quenched. The method has a detection range that is linear from 10 nM to
      1000 nM (with a correlation coefficient of 0.997). The limit of detection (LOD),
      calculated on the basis of a signal to noise ratio of 3, is 4.2 nM. The procedure
      was validated by the quantitation of OTA in spiked real samples and were found to
      be free of interference by the sample matrix. Recoveries ranged from 93.8 to
      113.0% in beer and from 92.0 to115.9% in red wine. Graphical abstract After
      adding ochratoxin A (OTA), the aptamer region in hairpin probe (HP) combined with
      OTA and thus exposed a single-stranded sequence to hybridize with signal probe
      (SP). Exonuclease III (Exo III) digested SP to liberate the free fluorophore
      (FAM).

PMID- 29594394
TI  - Cingulate abnormalities in bipolar disorder relate to gender and outcome: a voxel
      based morphometry study.
AB  - Structural magnetic resonance imaging (MRI) studies reported gray matter (GM)
      loss in bipolar disorder (BD) in cingulate cortices, key regions subserving
      emotional regulation and cognitive functions in humans. The aim of this study was
      to further explore cingulate GM volumes in a sizeable group of BD patients with
      respect to healthy controls, particularly investigating the impact of gender and
      clinical variables. 39 BD patients (mean Age = 48.6 +/- 9.7, 15 males and 24
      females) and 39 demographically matched healthy subjects (mean Age = 47.9 +/-
      9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the
      cingulate cortex were manually detected, including anterior and posterior
      regions. BD patients had decreased left anterior cingulate volumes compared with
      healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect
      was observed, with male patients showing reduced left anterior cingulate cortex
      (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a
      significant inverse correlation between right ACC volumes and number of
      hospitalizations were found in the whole group of BD patients (r = - 0.51, p =
      0.04) and in male BD patients (r = - 0.88, p = 0.04). Finally, no statistically
      significant correlations were observed in female BD patients. Our findings
      further confirm the putative role of the ACC in the pathophysiology of BD.
      Interestingly, this study also suggested the presence of gender-specific GM
      volume reductions in ACC in BD, which may also be associated to poor outcome.

PMID- 29594395
TI  - [Obstacles and perspectives of new antimicrobial concepts within research and
      development].
AB  - Antimicrobial resistance (AMR) has developed into a serious problem for the
      healthcare sector worldwide. Research on fundamentally novel antibiotics has been
      insufficient for decades and only a few new compounds have reached the market.
      Thus, the pressure to implement novel and effective concepts for the reduction of
      infections through problematic pathogens has dramatically increased. This demand
      has been recognized by politicians and comprehensive national and international
      funding programs have been launched. A major role of many funding lines is the
      investigation and development of therapeutics exerting a novel mechanism of
      action and/or minimizing the frequency of resistance. In addition to the actual
      clinical pipeline, this article lists selected examples from research and early
      development with a special focus on antibiotics. Moreover, alternative approaches
      like antivirulence and phage therapy as well as immunomodulation are summarized.
      AMR is no longer solely a healthcare policy, but is of societal significance as a
      whole. A consolidation of infrastructures and public-private partnerships, a
      reduction of regulatory obstacles and a continuous pursuit of innovations for
      antimicrobial therapy are urgently needed.

PMID- 29594396
TI  - Immobilization of zirconium-glycerolate nanowires on magnetic nanoparticles for
      extraction of urinary ribonucleosides.
AB  - The authors have immobilized nanowires made from zirconium glycerolate (ZrGly) on
      magnetite (Fe3O4) nanoparticles by applying a solvothermal growth process using
      metal-glycerolate as a precursor. The structure and the dissolution
      recrystallization mechanism of the resulting Fe3O4@ZrGly composite were
      investigated by attenuated total reflection-FTIR, energy-dispersive X-ray
      analysis, thermogravimetric analysis and solid-state cross polarization/magic
      angle spinning 13C NMR spectroscopy. The interaction between the zirconium
      glycerolate in Fe3O4@ZrGly and cis-diols leads to efficient adsorption of
      riboncleosides which then can be quantified by HPLC with UV detection. The
      sorbent was successfully applied to the selective enrichment of adenosine,
      cytidine, uridine and guanosine from spiked human urine samples. The detection
      limit of the method is in the range from 1.7 to 19 ng.mL-1 of nucleosides in
      spiked human urine, with relative standard deviations of lower than 12.4% and
      recoveries ranging from 90.6 to 113%. Graphical abstract Fe3O4@ZrGly with high
      selectivity towards ribonucleosides was designed and applied for quantitation of
      urinary ribonucleosides.

PMID- 29594397
TI  - Microwave-assisted synthesis of graphene modified CuO nanoparticles for
      voltammetric enzyme-free sensing of glucose at biological pH values.
AB  - The effect of graphene nanosheets on the glucose sensing performance of CuO
      powders was investigated. CuO and graphene-modified CuO nanoparticles (NPs) were
      fabricated by microwave-assisted synthesis and characterized by X-ray
      diffraction, transmission electron microscopy and X-ray photoelectron
      spectroscopy. The material was placed on a glassy carbon electrode (GCE) which
      then was characterized by cyclic voltammetry and chronoamperometry with respect
      to the capability of sensing glucose both at pH 13 and pH 7.4. The results
      revealed that the modified GCE has a fast and selective linear response to
      glucose at pH 13 that covers the 0.21 MUM to 12 mM concentration range, with a
      0.21 MUM low detection limit. The presence of graphene nanosheets results in an
      improved sensitivity which is to 700 MUA mM-1 cm-2. In solution of pH 7.4, the
      respective data are a linear analytical range from 5 to 14 mM; a 5 MUM LOD and a
      sensitivity of 37.63 MUA mM-1 cm-2 at working potential of -0.05 V (vs. Ag/AgCl)
      and scan rate of 50 mV s-1. Ascorbic acid, dopamine, uric acid, sucrose, maltose
      and fructose do not interfere. Graphical abstract ?.

PMID- 29594398
TI  - Impedimetric PSA aptasensor based on the use of a glassy carbon electrode
      modified with titanium oxide nanoparticles and silk fibroin nanofibers.
AB  - This article describes an impedimetric aptasensor for the prostate specific
      antigen (PSA), a widely accepted prostate cancer biomarker. A glassy carbon
      electrode (GCE) was modified with titanium oxide nanoparticles (TiO2) and silk
      fibroin nanofiber (SF) composite. The aptasensor was obtained by immobilizing a
      PSA-binding aptamer on the AuNP-modified with 6-mercapto-1-hexanol. The single
      fabrication steps were characterized by cyclic voltammetry and electrochemical
      impedance spectroscopy. The assay has two linear response ranges (from 2.5 fg.mL
      1 to 25 pg.mL-1, and from 25 pg.mL-1 to 25 ng.mL-1) and a 0.8 fg.mL -1 detection
      limit. After optimization of experimental conditions, the sensor is highly
      selective for PSA over bovine serum albumin and lysozyme. It was successfully
      applied to the detection of PSA in spiked serum samples. Graphical abstract
      Schematic of the fabrication of an aptasensor for the prostate specific antigen
      (PSA). It is based on the use of a glassy carbon electrode modified with gold
      nanoparticles and titanium oxide-silk fibroin. The immobilization process of
      aptamer and interaction with PSA were followed by electrochemical impedance
      spectroscopy technique.

PMID- 29594399
TI  - Empagliflozin, metformin and insulin degludec, during pregnancy: a case report.

PMID- 29594400
TI  - A cascade amplification strategy of catalytic hairpin assembly and hybridization
      chain reaction for the sensitive fluorescent assay of the model protein
      carcinoembryonic antigen.
AB  - A cascade nucleic acid amplification strategy is presented for fluorometric
      aptamer based determination of the model protein carcinoembryonic antigen (CEA).
      Amplification is accomplished by combining catalytic hairpin assembly (CHA) and
      hybridization chain reaction (HCR). In this assay, a specially designed single
      stranded DNA containing the aptamer sequence (AS) specific for CEA is hybridized
      with an inhibitor strand (IS) to form a double-stranded DNA (IS@AS). In the
      presence of CEA, it will recognize and bind to the AS strand which causes the
      release of IS. By introducing two DNA hairpins (H1 and H2; these containing
      complementary sequences) CHA will be activated via the hybridization reactions of
      H1 and H2. This is accompanying by the formation of a double-stranded DNA (H1-H2)
      and the release of CEA@AS. The liberated CEA@AS further drives successive
      recycling of the CHA, thereby generating further copies of H1-H2. The resultant
      H1-H2 hybrids act as primers and trigger HCR with the help of other two DNA
      hairpins (H3 and H4) containing G-rich toehold at the 5'-terminus and 3'-terminus
      of H3 and H4, respectively. The fluorescent probe N-methyl mesoporphyrin IX (NMM)
      is finally intercalated into the G-rich domains of the long DNA nanostructures
      due to formation of G-quadruplex structures. This generates a fluorescent signal
      (best measured at excitation/emission wavelengths of 399/610 nm) that increases
      with the concentration of target (CEA). This aptamer-based fluorescence assay is
      highly sensitive and has a linear range that covers the 1 pg.mL-1 to 2 ng.mL-1
      CEA concentration range, with a 0.3 pg.mL-1 detection limit. Graphical abstract
      By integrating catalytic hairpin assembly (CHA) and hybridization chain reaction
      (HCR) for effective signal enhancement, a novel cascade amplification strategy is
      presented to develop a sensitive and selective fluorescent method for the assay
      of the model protein carcinoembryonic antigen (CEA).

PMID- 29594401
TI  - Radiation exposure during CT-guided biopsies: recent CT machines provide markedly
      lower doses.
AB  - OBJECTIVES: To examine radiation dose levels of CT-guided interventional
      procedures of chest, abdomen, spine and extremities on different CT-scanner
      generations at a large multicentre institute. MATERIALS AND METHODS: 1,219 CT
      guided interventional biopsies of different organ regions ((A) abdomen (n=516),
      (B) chest (n=528), (C) spine (n=134) and (D) extremities (n=41)) on different CT
      scanners ((I) SOMATOM-Definition-AS+, (II) Volume-Zoom, (III) Emotion6) were
      included from 2013-2016. Important CT-parameters and standard dose-descriptors
      were retrospectively examined. Additionally, effective dose and organ doses were
      calculated using Monte-Carlo simulation, following ICRP103. RESULTS: Overall,
      radiation doses for CT interventions are highly dependent on CT-scanner
      generation: the newer the CT scanner, the lower the radiation dose imparted to
      patients. Mean effective doses for each of four procedures on available scanners
      are: (A) (I) 9.3mSv versus (II) 13.9mSv (B) (I) 7.3mSv versus (III) 11.4mSv (C)
      (I) 6.3mSv versus (II) 7.4mSv (D) (I) 4.3mSv versus (II) 10.8mSv. Standard dose
      descriptors [standard deviation (SD); CT dose indexvol (CTDIvol); dose-length
      product (DLPbody); size-specific dose estimate (SSDE)] were also compared.
      CONCLUSION: Effective dose, organ doses and SSDE for various CT-guided
      interventional biopsies on different CT-scanner generations following
      recommendations of the ICRP103 are provided. New CT-scanner generations involve
      markedly lower radiation doses versus older devices. KEY POINTS: * Effective
      dose, organ dose and SSDE are provided for CT-guided interventional examinations.
      * These data allow identifying organs at risk of higher radiation dose. *
      Detailed knowledge of radiation dose may contribute to a better individual risk
      stratification. * New CT-scanner generations involve markedly lower radiation
      doses compared to older devices.

PMID- 29594402
TI  - Contrast-enhanced cone-beam breast-CT (CBBCT): clinical performance compared to
      mammography and MRI.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of contrast-enhanced (CE) cone
      beam breast computed tomography (CBBCT) in dense breast tissue and compare it to
      non-contrast (NC) CBBCT, mammography (MG) and magnetic resonance imaging (MRI).
      METHODS: This prospective institutional review board-approved study included 41
      women (52 breasts) with American College of Radiology (ACR) density types c or d
      and Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 assessments in MG
      or ultrasound (US). Imaging modalities were independently evaluated by two
      blinded readers. RESULTS: A total of 100 lesions (51 malignant, 6 high-risk, and
      43 benign) were identified. For readers 1/2, respectively, and p values comparing
      CE-CBBCT to other modalities: diagnostic accuracy (AUC) for CE-CBBCT was
      0.83/0.77, for MRI 0.88/0.89 (p = 0.2272/0.002), for NC-CBBCT 0.73/0.66 (p =
      0.038/ 0.0186) and for MG 0.69/0.64 (p = 0.081/0.0207). CE-CBBCT sensitivity
      (0.88/0.78) was 37-39% higher in comparison to MG (0.49/0.41, p < 0.001 both) but
      inferior to MRI (0.98/0.96, p = 0.0253/0.0027). CE-CBBCT specificity (0.71/0.71)
      was numerically higher compared to MRI (0.61/0.69, p = 0.0956/0.7389).
      CONCLUSIONS: CBBCT diagnostic performance varied with the respective reader and
      experience. CE-CBBCT improved AUC and sensitivity in comparison to MG and NC
      CBBCT, and was comparable to MRI in dense breast tissue. In tendency, specificity
      was higher for CE-CBBCT than MRI. KEY POINTS: * CE-CBBCT diagnostic accuracy
      (AUC) was comparable to MRI in dense breasts. * CE-CBBCT improved sensitivity and
      AUC in comparison to MG and NC-CBBCT. * CE-CBBCT has inferior sensitivity but
      higher specificity than MRI. * CE-CBBCT is a potential imaging alternative for
      patients with MRI contraindications.

PMID- 29594403
TI  - Cloning and Characterization of Two MAPK Genes UeKpp2 and UeKpp6 in Ustilago
      esculenta.
AB  - Ustilago esculenta, resembling a fungal endophyte in Zizania latifolia, inhibits
      the host plant flowering and induces the host stems to swell and form edible
      galls. It is well believed that when and how the fungus infects and proliferates
      in the host plants during the host development is of importance in the edible
      gall formation. Mitogen-activated protein kinases (MAPKs) have been found to play
      an important role in sensing environment cues and regulating infection. Two MAPK
      genes UeKpp2 and UeKpp6 from U. esculenta were cloned and suggested to be
      involved in the Fus3/Kss1 pathway by a phylogenetic analysis with the neighbor
      joining method. Quantitative RT-PCR (qRT-PCR) analyses indicated that expression
      of UeKpp2 and UeKpp6 were induced during mating and infection processes, and
      their expression patterns displayed differentially under different carbon and
      nitrogen sources. In addition, subcellular localization of UeKpp2 or UeKpp6 fused
      with the reporter green fluoresce protein was observed by confocal laser scanning
      microscope, and yeast two-hybrid assays were carried out. Results showed that
      both UeKpp2 and UeKpp6 were located in cytoplasm and interacted with UePrf1,
      indicating their involvement in hyphal growth and host-pathogen regulation. Only
      UeKpp2 but not UeKpp6 interacted with the upstream MAPK kinase UeFuz7, implying
      an additional MAPK pathway, in which UeKpp6 involved, existed.

PMID- 29594404
TI  - Single Sampling Versus Multiple Testing Strategy to Assess Gut Microbiota
      Composition: Does It Matter?

PMID- 29594405
TI  - Quantitative qPCR Analysis of Ruminal Microorganisms in Beef Cattle Grazing in
      Pastures in the Rainy Season and Supplemented with Different Protein Levels.
AB  - We tested the hypothesis that supplementation with three protein levels improves
      fermentation parameters without changing the rumen microbial population of
      grazing beef cattle in the rainy season. Four rumen-cannulated Nellore bulls (432
      +/- 21 kg of body weight) were used in a 4 * 4 Latin square design with four
      supplements and four experimental periods of 21 days each. The treatments were
      mineral supplement (ad libitum) and supplements with low, medium (MPS), and high
      protein supplement (HPS), supplying 106, 408, and 601 g/day of CP, respectively.
      The abundance of each target taxon was calculated as a fraction of the total 16S
      rRNA gene copies in the samples, using taxon-specific and domain bacteria
      primers. Supplemented animals showed lower (P < 0.05) proportions of Ruminococcus
      flavefaciens and greater (P < 0.05) proportions of Ruminococcus albus and
      Butyrivibrio fibrisolvens than animals that received only the mineral supplement.
      The HPS supplement resulted in higher (P < 0.05) proportions of Fibrobacter
      succinogenes, R. flavefaciens, and B. fibrisolvens and lower (P < 0.05)
      proportions of R. albus than the MPS supplement. Based on our results, high
      protein supplementation improves the ruminal conditions and facilitates the
      growth of cellulolytic bacteria in the rumen of bulls on pastures during the
      rainy season.

PMID- 29594406
TI  - Graphene and graphene oxide as a solid matrix for extraction of membrane and
      membrane-associated proteins.
AB  - The extraction of membrane proteins remain a challenge due to innate
      hydrophobicity, dynamic discrepancy, and restrain effect of membrane lipids.
      Nanomaterials with high surface area have competency of hydrophobic-hydrophobic
      lipid interactions. It is shown here that both graphene and graphene oxide
      dissolved in solubilization buffer are viable sorbents for efficient extraction
      of membrane proteins. LC-MS/MS analysis further revealed that graphene (50-200
      nm) and graphene oxide (50-200 nm) can enrich more kinds of membrane proteins
      than a commercially available kit. Graphene was further applied to the enrichment
      of membrane proteins of normal cells as well as cancer cells, and 1079 and 872
      proteins were identified, respectively, among which 56.5% and 60.5% were membrane
      proteins. In particular, 241 proteins were significantly regulated in cancer
      cells. Gene expression of 15 proteins was verified by qRT-PCR, and 4 of them were
      further quantified by immunoassay. These data collectively demonstrate that
      graphene has great potential to improve membrane protein extractions and thus can
      serve downstream cancer proteomics. Graphical abstract Two dimensional carbon
      nanomaterials, including graphene and graphene oxide, were employed as solid
      matrix to avoid lipid bilayer interference and enhance the extraction efficiency
      of membrane and membrane associated proteins. The strategy will benefit
      downstream membrane proteomics analysis.

PMID- 29594407
TI  - [Fatal flecainide intoxication in a 17-year-old girl].
AB  - A 17-year-old girl was found vomiting and somnolent at home and was taken to a
      hospital. The girl initially presented with ventricular tachycardia with broad
      QRS complexes which was very difficult to control. During the course a subsequent
      cardiogenic shock developed and despite exhaustion of all therapeutic options the
      fatal outcome could not be averted. The medicolegal autopsy revealed no evidence
      of any form of violence but the signs of medical treatment. Furthermore, no
      pathology of internal organs was detected. The toxicological analyses revealed a
      lethal intoxication with flecainide as the cause of death. The investigations of
      the police indicated that the girl took flecainide in suicidal intention.

PMID- 29594408
TI  - [Hypotheses must be tested].

PMID- 29594409
TI  - The optimal TSH level necessary for successful radioiodine ablation of
      differentiated thyroid carcinoma, as well as the time to reach this level, is a
      work in progress.

PMID- 29594410
TI  - 18F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2:
      additional value of electroclinical data and coregistration with MRI.
AB  - PURPOSE: To assess the localizing value of 18F-FDG PET in patients operated on
      for drug-resistant epilepsy due to focal cortical dysplasia type 2 (FCD2).
      METHODS: We analysed 18F-FDG PET scans from 103 consecutive patients (52 males, 7
      65 years old) with histologically proven FCD2. PET and MRI data were first
      reviewed by visual analysis blinded to clinical information and FCD2 location.
      The additional value of electroclinical data and PET/MRI coregistration was
      assessed by comparison with pathological results and surgical outcomes. RESULTS:
      Visual analysis of PET scans showed focal or regional hypometabolism
      corresponding to the FCD2 in 45 patients (44%), but the findings were doubtful or
      misleading in 37 patients and negative in 21. When considering electroclinical
      data, positive localization was obtained in 73 patients, and this increased to 85
      (83%) after coregistration of PET and MRI data. Under the same conditions, MRI
      was positive in 61 patients (59%), doubtful in 15 and negative in 27. The
      additional value of PET was predominant in patients negative or doubtful on MRI,
      localizing the FCD2 in 35 patients (83%). Interobserver agreement correlated with
      the grade of hypometabolism: it was good in patients with mild to severe
      hypometabolism (82-95%), but moderate in those with subtle/doubtful
      hypometabolism (45%). The main factors influencing positive PET localization were
      the grade of hypometabolism and the size of the FCD2 (P < 0.0001). Misleading
      location (nine patients) was associated with a small FCD2 in the mesial frontal
      and central regions. Following limited cortical resection mainly located in
      extratemporal areas (mean follow-up 5.6 years), a seizure-free outcome was
      achieved in 94% of patients, including Engel's class IA in 72%. CONCLUSION: In
      this series, 18F-FDG PET contributed to the localization of FCD2 in 83% of
      patients. This high localizing value was obtained by integration of
      electroclinical data and PET/MRI coregistration. This approach may help improve
      the surgical outcome in extratemporal epilepsy, even in patients negative on MRI.

PMID- 29594411
TI  - Recent advances in the UltraScan SOlution MOdeller (US-SOMO) hydrodynamic and
      small-angle scattering data analysis and simulation suite.
AB  - The UltraScan SOlution MOdeller (US-SOMO) is a comprehensive, public domain, open
      source suite of computer programs centred on hydrodynamic modelling and small
      angle scattering (SAS) data analysis and simulation. We describe here the
      advances that have been implemented since its last official release (#3087,
      2017), which are available from release #3141 for Windows, Linux and Mac
      operating systems. A major effort has been the transition from the legacy Qt3
      cross platform software development and user interface library to the modern Qt5
      release. Apart from improved graphical support, this has allowed the direct
      implementation of the newest, almost two-orders of magnitude faster version of
      the ZENO hydrodynamic computation algorithm for all operating systems. Coupled
      with the SoMo-generated bead models with overlaps, ZENO provides the most
      accurate translational friction computations from atomic-level structures
      available (Rocco and Byron Eur Biophys J 44:417-431, 2015a), with computational
      times comparable with or faster than those of other methods. In addition, it has
      allowed us to introduce the direct representation of each atom in a structure as
      a (hydrated) bead, opening interesting new modelling possibilities. In the small
      angle scattering (SAS) part of the suite, an indirect Fourier transform Bayesian
      algorithm has been implemented for the computation of the pairwise distance
      distribution function from SAS data. Finally, the SAS HPLC module, recently
      upgraded with improved baseline correction and Gaussian decomposition of not
      baseline-resolved peaks and with advanced statistical evaluation tools (Brookes
      et al. J Appl Cryst 49:1827-1841, 2016), now allows automatic top-peak frame
      selection and averaging.

PMID- 29594412
TI  - Ferritin from the haemolymph of adult ants: an extraction method for
      characterization and a ferromagnetic study.
AB  - Ferritin has been studied in many animals, plants and bacteria. The main
      functions of ferritin in mammals are iron concentration and stabilization,
      protection against oxidants and iron storage for later developmental or iron
      dependent activities. Although insect ferritin plays a key role in iron
      transport, only a few studies to date have examined its properties and function.
      Ferritin isolation from the haemolymph of adult Camponotus sericeiventris ants
      involved heating at 75  degrees C, followed by protein fractionation with 3.2 M
      KBr gradients and ferritin sedimentation with KBr. Protein identification was
      performed using high-resolution proteomics techniques. SDS-PAGE revealed three
      subunits with molecular weights (MW) of 26, 28 and 31 kDa. Native PAGE indicated
      a MW higher than 669 kDa. Proteomic analysis strongly suggested the 26 and 31 kDa
      bands as F2LCH and F1HCH subunits of ferritin, respectively. Ferromagnetic
      resonance (FMR) at 100 K showed, at low field, a characteristic broad component
      of the ferritin iron core, suggesting that its distribution was shifted to values
      greater than 3000, a higher content than in mammals. The protein yield and MW
      were comparable to those reported in other studies of insects. To the best of our
      knowledge, this is the first report on ferritin extracted from adult ants to
      date. These results are discussed on the basis of the protein structure-function
      relation of secreted insect and mammal ferritins. This purification method will
      allow the use of magnetic techniques, which are relevant for understanding the
      role of ferritin in the biomineralization of magnetic nanoparticles in insects.

PMID- 29594414
TI  - Aptamer-functionalized magnetic and fluorescent nanospheres for one-step
      sensitive detection of thrombin.
AB  - A one-step sandwich method is described for detecting proteins with magnetic
      nanospheres (MNs) and fluorescent nanospheres (FNs). Thrombin is selected as a
      model analyte to validate the method. Two DNA aptamers (Apt 29 and Apt 15
      targeting two different exosites of thrombin) are chosen as recognition elements
      to modify MNs and FNs. The superparamagnetic MN-Apt 29 conjugate is used to
      separate and concentrate thrombin. The FN-Apt 15 conjugate encapsulates hundreds
      of fluorescent quantum dots and is used as reporter to provide a stable signal.
      Magnetic capture and fluorescence identification are performed simultaneously to
      form a sandwich complex (MN-Apt 29-thrombin-FN-Apt 15) for fluorescence
      determination (at excitation/emission wavelengths of 380/622 nm). The method is
      convenient, time saving, and gives a strong signal (compared to the two-step
      method where capture and identification are performed in two steps). The one-step
      method presented here is completed within 30 min and has a 3.5 ng.mL-1 (97 pM)
      detection limit. The method is reproducible, has an intra-assay variability of
      1.5%, and an inter-assay variability of 4.9%. Other serum proteins (HSA, CEA,
      PSA, and AFP) do not interfere. The method was also applied to analyze serum
      samples. Almost the same fluorescence intensity was measured when analyzing 1%
      serum samples (compared to buffer samples). Graphical abstract Magnetic
      nanospheres with excellent superparamagnetic property and fluorescent QD-based
      nanospheres were prepared and used in a one-step sensitive method for detecting
      thrombin. The method exhibits good reproducibility, high specificity, and good
      selectivity.

PMID- 29594413
TI  - Risk factors for postoperative pneumonia in elderly patients with colorectal
      cancer: a sub-analysis of a large, multicenter, case-control study in Japan.
AB  - PURPOSE: Postoperative pneumonia affects the length of stay and mortality after
      surgery in elderly patients with colorectal cancer (CRC). We aimed to determine
      the risk factors of postoperative pneumonia in elderly patients with CRC, and to
      evaluate the impact of laparoscopic surgery on elderly patients with CRC.
      METHODS: We retrospectively investigated 1473 patients >= 80 years of age who
      underwent surgery for stage 0-III CRC between 2003 and 2007. Using a multivariate
      analysis, we determined the risk factors for pneumonia occurrence from each
      baseline characteristic. RESULTS: Among all included patients, 26 (1.8%)
      experienced postoperative pneumonia, and restrictive respiratory impairment,
      obstructive respiratory impairment, history of cerebrovascular events, and open
      surgery were determined as risk factors (odds ratio [95% confidence interval],
      2.78 [1.22-6.20], 2.71 [1.22-6.30], 3.60 [1.37-8.55], and 3.57 [1.22-15.2],
      respectively). Furthermore, postoperative pneumonia was more frequently
      accompanied by increasing cumulative numbers of these risk factors (area under
      the receiver operating characteristic curve = 0.763). CONCLUSIONS: Laparoscopic
      surgery may be safely performed in elderly CRC patients, even those with
      respiratory impairment and a history of cerebrovascular events.

PMID- 29594415
TI  - Restricted MHC class I A locus diversity in olive and hybrid olive/yellow baboons
      from the Southwest National Primate Research Center.
AB  - Baboons are valuable models for complex human diseases due to their genetic and
      physiologic similarities to humans. Deep sequencing methods to characterize full
      length major histocompatibility complex (MHC) class I (MHC-I) alleles in
      different nonhuman primate populations were used to identify novel MHC-I alleles
      in baboons. We combined data from Illumina MiSeq sequencing and Roche/454
      sequencing to characterize novel full-length MHC-I transcripts in a cohort of
      olive and hybrid olive/yellow baboons from the Southwest National Primate
      Research Center (SNPRC). We characterized 57 novel full-length alleles from 24
      baboons and found limited genetic diversity at the MHC-I A locus, with
      significant sharing of two MHC-I A lineages between 22 out of the 24 animals
      characterized. These shared alleles provide the basis for development of tools
      such as MHC:peptide tetramers for studying cellular immune responses in this
      important animal model.

PMID- 29594416
TI  - Microwave-assisted synthesis of highly luminescent N- and S-co-doped carbon dots
      as a ratiometric fluorescent probe for levofloxacin.
AB  - Uniform N- and S-co-doped carbon dots (NSCDs) with fluorescence quantum yields of
      up to 64% were synthesized via a one-step microwave-assisted method. Ammonium
      citrate and L-cysteine act as precursors, and synthesis is completed in 2.5 min
      using a 750 W microwave oven to give a 62% yield. The NSCDs show bright blue
      fluorescence (with excitation/emission peaks at 353/426 nm) and have narrow size
      distribution. On exposure to levofloxacin (LEV), the emission maximum shifts to
      499 nm. This effect was used to design ratiometric (2-wavelength) assays for LEV.
      The fluorometric method (based on measurement of the fluorescence intensity ratio
      at 499 and 426 nm) has a detection limit of 5.1 MUg.L-1 (3sigma/k) and a linear
      range that extends from 0.01 to 70 mg.L-1. The method was applied to the
      determination of LEV in three kinds of spiked water samples and has recoveries in
      the range from 98.6 to 106.8%. The fluorescent probe described here is highly
      selective and sensitive. Graphical Abstract Highly luminescent N- and S-co-doped
      carbon dots were synthesized using AC (ammonium citrate) and Cys (L-cysteine) by
      microwave-assisted method, and were applied to the visual and ratiometric
      fluorescence determination of LEV (levofloxacin).

PMID- 29594417
TI  - Layered vanadium(IV) disulfide nanosheets as a peroxidase-like nanozyme for
      colorimetric detection of glucose.
AB  - The authors have discovered that vanadium disulfide (VS2) nanosheets, synthesized
      by a hydrothermal method, exert stable peroxidase-like activity. The catalytic
      activity, with H2O2 as a cosubstrate, follows Michaelis-Menten kinetics and
      varies with temperature, pH value and H2O2 concentration. Two-dimensional VS2
      sheets acting as peroxidase (POx) mimics can replace horseradish peroxidase due
      to their availability, robustness, and reusability. The POx-like activity of VS2
      sheets was exploited to design a colorimetric glucose assay by using 3,3',5,5'
      tetramethylbenzidine as a substrate and by working at an analytical wavelength of
      652 nm. The assay covers the 5 to 250 MUM glucose concentration range with a 1.5
      MUM detection limit. It was applied to the analysis of glucose in fruit juice. In
      our perception, the peroxidase-like nanozyme out of the family of transition
      metal dichalcogenides presented here has a wide scope in that it may stimulate
      promising biocatalytic applications in biotechnology and analytical chemistry.
      Graphical abstract Layered VS2 nanosheets were prepared via hydrothermal
      synthesis and are shown to exert superior peroxidase-mimicking activity. Using
      these POx nano-mimics, a sensitive colorimetric assay for glucose was developed
      and applied to fruit juice analysis. This work unlocks the access of VS2 to
      biocatalysis and bioassays.

PMID- 29594418
TI  - Colorimetric determination of the activity of alkaline phosphatase based on the
      use of Cu(II)-modulated G-quadruplex-based DNAzymes.
AB  - A colorimetric detection scheme is introduced for the determination of alkaline
      phosphatase (ALP) activity based on Cu(II)-modulated G-quadruplex-based DNAzymes.
      It is exploiting the strong affinity of Cu(II) for pyrophosphate (PPi) upon which
      the cofactor PPi is trapped by Cu(II). Hence, the activity of the DNAzyme is
      inhibited. ALP catalyzes the hydrolysis of PPi, causing the release of Cu(II).
      DNAzyme, in turn, is activated and catalyzes the cleavage of the DNA probe
      substrate. The released G-rich sequence folds into the G-quadruplex, which can
      bind hemin and catalyze the oxidation of 2,2'-azinobis (3-ethylbenzothiozoline)-6
      sulfonate (ABTS), and this leads to an increase in absorbance at 420 nm.
      Absorbance increases linearly with increasing ALP activity in 0.07 to 300 U.L-1
      range, with a 70 mU.L-1 detection limit. The method was applied in ALP inhibition
      tests and to the determination of ALP activity in spiked serum samples where it
      gave satisfactory results. Graphical abstract A colorimetric method has been
      developed for the detection of alkaline phosphatase based on the use of Cu(II)
      modulated G-quadruplex-based DNAzymes.

PMID- 29594419
TI  - Highly crystalline graphitic carbon nitride quantum dots as a fluorescent probe
      for detection of Fe(III) via an innner filter effect.
AB  - Bulk g-C3N4 was transformed into water-soluble graphitic carbon nitride quantum
      dots (g-CNQDs) via a chemical oxidation and liquid exfoliation process. The g
      CNQDs possess a size distribution ranging from 1 to 5 nm (centered at 3 nm),
      excellent crystallinity, and are water soluble. It is found that Fe(III) ions are
      adsorbed on the surface of the g-CNQDs via electrostatic interaction, and that
      the blue fluorescence of the g-CNQDs is reduced by Fe(III) via an inner filter
      effect. By using the g-CNQDs as a fluorescent probe, Fe(III) can be determined at
      excitation/emission wavelengths of 241/368 nm in spiked natural water samples
      within 1 min and with good selectivity over other ions. Response is linear in the
      0.2-60 MUmol.L-1 Fe(III) concentration range, and the detection limit is 23
      nmol.L-1. Graphical abstract Graphitic carbon nitride quantum dots (g-CNQDs) emit
      blue fluorescence at an excitation wavelength of 241 nm. Fe(III) ions are quickly
      adsorbed on the g-CNQDs via electrostatic interaction, and fluorescence is
      quenched due to an inner filter effect.

PMID- 29594420
TI  - Colloidal crystal templated molecular imprinted polymer for the detection of 2
      butoxyethanol in water contaminated by hydraulic fracturing.
AB  - The authors describe a molecularly imprinted polymer (MIP) that enables detection
      of 2-butoxyethanol (2BE), a pollutant associated with hydraulic fracturing
      contamination. Detection is based on a combination of a colloidal crystal
      templating and a molecular imprinting. The MIPs are shown to display higher
      binding capacity for 2BE compared to non-imprinted films (NIPs), with imprinting
      efficiencies of ~ 2. The tests rely on the optical effects that are displayed by
      the uniformly ordered porous structure of the material. The reflectance spectra
      of the polymer films have characteristic Bragg peaks whose location varies with
      the concentration of 2BE. Peaks undergo longwave red shifts up to 50 nm on
      exposure of the MIP to 2BE in concentrations in the range from 1 ppb to 100 ppm.
      This allows for quantitative estimates of the 2BE concentrations present in
      aqueous solutions. The material is intended for use in the early detection of
      contamination at hydraulic fracturing sites. Graphical abstract Molecularly
      imprinted polymers (MIPs) sensor with the sensing ability on reflectance spectra
      responding to the presence of 2-butoxyethanol (2BE) for early detection of
      hydraulic fracking contamination.

PMID- 29594421
TI  - Direct determination of the tumor marker AFP via silver nanoparticle enhanced
      SERS and AFP-modified gold nanoparticles as capturing substrate.
AB  - The authors describe a rapid and direct SERS-based immunoassay for the
      determination of AFP, an important marker for diagnosis of hepatocellular
      carcinoma. Silver nanoparticles (AgNPs; 36 nm i.d.) serve as a support to
      immobilize antibody and as a SERS intensifier, and AFP-modified gold
      nanoparticles are employed as capturing substrate. Direct and quantitative
      detection of AFP is accomplished with a limit detection as low as 5 ng.mL-1.
      Compared to assays based on the use of metal nanoparticles, the use of gold
      silver nanoparticle heterodimers as an active SERS substrate can save costs
      because only a single antibody is required. Moreover, the high selectivity and
      good linear relationship of detecting AFP in fetal bovine serum indicates its
      potential applicability for the direct analysis of clinical samples. Graphical
      abstract Direct and quantitative determination of AFP antigen utilizing SERS has
      been was successfully presented and applied to detect alpha fetoprotein antigen
      in fetal bovine serum with detection limit of 2 ng*mL-1.

PMID- 29594422
TI  - Electrochemical determination of dopamine using a glassy carbon electrode
      modified with a nanocomposite consisting of nanoporous platinum-yttrium and
      graphene.
AB  - A nanoporous platinum-yttrium alloy (NP-PtY) was fabricated by dealloying ribbons
      of a PtYAl alloy. Owing to the high porosity and the synergistic effect of Y in
      the Pt backbone, the NP-PtY exhibits superior structural stability,
      reproducibility and electrocatalytic activity. An electrochemical sensor was
      developed for the highly sensitive and selective detection of dopamine (DA) based
      on the use of a glassy carbon electrode modified with NP-PtY alloy and graphene.
      The sensor, best operated at 0.16 V vs. SCE, has a linear range covering the 0.9
      to 82 MUM concentration range, a 0.36 MUM detection limit (at S/N = 3), and good
      selectivity over tyramine, tryptamine, phenethylamine, uric acid, and ascorbic
      acid. It gave satisfactory results in the determination of DA in spiked samples
      of urine. Graphical abstract Nanoporous platinum-yttrium alloy (NP-PtY) was
      fabricated by means of a one-step dealloying process. A glassy carbon electrode
      modified with the NP-PtY and graphene nanocomposite exhibits a wide linear range
      and a low detection limit towards dopamine. The sensor has remarkable
      reproducibility, stability and selectivity.

PMID- 29594425
TI  - A Journey Through Innovations: Remembering Hardships and Compassion.

PMID- 29594423
TI  - Epidemiological observations on cryptosporidiosis and molecular characterization
      of Cryptosporidium spp. in sheep and goats in Kuwait.
AB  - Molecular epidemiological analysis of cryptosporidiosis in Middle Eastern
      countries suggests that small ruminants could play a major role in the
      transmission of Cryptosporidium spp. to humans, with a dominance of
      Cryptosporidium parvum, especially its IId subtypes. However, little information
      is available on the epidemiology and risk factors of cryptosporidiosis as well
      the distribution of Cryptosporidium species/genotypes and subtypes in small
      ruminants in this area, including Kuwait. In the present study, 47 farms from
      several areas in Kuwait were visited once during October 2014 to September 2015
      to collect data on risk factors associated with Cryptosporidium infection. Fecal
      samples from 334 sheep and 222 goats were examined for Cryptosporidium oocysts by
      Ziehl-Neelsen staining (ZN) and antigens by enzymatic immunoassay (EIA). The
      Cryptosporidium prevalence was higher when samples were examined by EIA than ZN
      (11.4 and 7.2% in sheep and goats by EIA, compared with 4.2 and 3.6% by ZN,
      respectively). Young age (less than 3 months) and closed housing system are risk
      factors of Cryptosporidium infection. A correlation between fecal consistency and
      the occurrence of Cryptosporidium spp. was observed; non-formed fecal samples
      were often found positive. Molecular characterization of 30 ovine and caprine
      samples using PCR-RFLP analysis of the small subunit rRNA gene revealed the
      presence of C. parvum in 23 samples, Cryptosporidium ubiquitum in five samples,
      and Cryptosporidium xiaoi in two samples. Sequence analysis of C. parvum at the
      60 KDa glycoprotein gene locus identified two subtypes, IIaA15G2R1 and IIdA20G1,
      with the latter being more common (in 2 and 20 successfully subtyped samples,
      respectively). Only one subtype of C. ubiquitum (XIIa) was recorded.
      Cryptosporidiosis in small ruminants apparently poses public health problem in
      Kuwait.

PMID- 29594426
TI  - Mineral Grains, Dimples, and Hot Volcanic Organic Streams: Dynamic Geological
      Backstage of Macromolecular Evolution.
AB  - The hypothesis of hot volcanic organic stream as the most probable and
      geologically plausible environment for abiogenic polycondensation is proposed.
      The primary synthesis of organic compounds is considered as result of an
      explosive volcanic (perhaps, meteorite-induced) eruption. The eruption was
      accompanied by a shock wave propagating in the primeval atmosphere and resulting
      in the formation of hot cloud of simple organic compounds-aldehydes, alcohols,
      amines, amino alcohols, nitriles, and amino acids-products, which are usually
      obtained under the artificial conditions in the spark-discharge experiments. The
      subsequent cooling of the organic cloud resulted in a gradual condensation and a
      serial precipitation of organic compounds (in order of decreasing boiling point
      values) into the liquid phase forming a hot, viscous and muddy organic stream
      (named "lithorheos"). That stream-even if the time of its existence was short-is
      considered here as a geologically plausible environment for abiogenic
      polycondensation. The substances successively prevailing in such a stream were
      cyanamide, acetamide, formamide, glycolonitrile, acetonitrile. An important role
      was played by mineral (especially, phosphate-containing) grains (named
      "lithosomes"), whose surface was modified with heterocyclic nitrogen compounds
      synthesized in the course of eruption. When such grains got into hot organic
      streams, their surface catalytic centers (named "lithozymes") played a decisive
      role in the emergence, facilitation and maintenance of prebiotic reactions and
      key processes characteristic of living systems. Owing to its cascade structure,
      the stream was a factor underlying the formation of mineral-polymeric aggregates
      (named "lithocytes") in the small natural streambed cavities (dimples)-as well as
      a factor of their further spread within larger geological locations which played
      a role of chemo-ecological niches. All three main stages of prebiotic evolution
      (primary organic synthesis, polycondensation, and formation of proto-cellular
      structures) are combined within a common dynamic geological process. We suppose
      macromolecular evolution had an extremely fast, "flash" start: the period from
      volcanic eruption to formation of lithocyte "populations" took not million years
      but just several tens of minutes. The scenario proposed can be verified
      experimentally with a three-module setup working with principles of dynamic
      (flow) chemistry in its core element.

PMID- 29594427
TI  - Fluorescence turn-on detection of target sequence DNA based on silicon nanodot
      mediated quenching.
AB  - We have developed a new enzyme-free method for target sequence DNA detection
      based on the dynamic quenching of fluorescent silicon nanodots (SiNDs) toward Cy5
      tagged DNA probe. Fascinatingly, the water-soluble SiNDs can quench the
      fluorescence of cyanine (Cy5) in Cy5-tagged DNA probe in homogeneous solution,
      and the fluorescence of Cy5-tagged DNA probe can be restored in the presence of
      target sequence DNA (the synthetic target miRNA-27a). Based on this phenomenon, a
      SiND-featured fluorescent sensor has been constructed for "turn-on" detection of
      the synthetic target miRNA-27a for the first time. This newly developed approach
      possesses the merits of low cost, simple design, and convenient operation since
      no enzymatic reaction, toxic reagents, or separation procedures are involved. The
      established method achieves a detection limit of 0.16 nM, and the relative
      standard deviation of this method is 9% (1 nM, n = 5). The linear range is 0.5-20
      nM, and the recoveries in spiked human fluids are in the range of 90-122%. This
      protocol provides a new tactic in the development of the nonenzymic miRNA
      biosensors and opens a promising avenue for early diagnosis of miRNA-associated
      disease. Graphical abstract The SiND-based fluorescent sensor for detection of S
      miR-27a.

PMID- 29594428
TI  - Analytical procedure for the determination of very volatile organic compounds (C3
      C6) in indoor air.
AB  - The substance group of very volatile organic compounds (VVOCs) is moving into the
      focus of indoor air analysis, facing ongoing regulations at international and
      European levels targeting on indoor air quality and human health. However, there
      exists at present no validated analysis for the identification and quantification
      of VVOCs in indoor air. Therefore, the present study targeted on the development
      of an analytical method in order to sample the maximum possible quantity of VVOCs
      in indoor air on solid sorbents with subsequent analysis by thermal desorption
      and coupled gas chromatography/mass spectrometry (TDS-GC/MS). For this purpose,
      it was necessary to investigate the performance of available sorbents and to
      optimize the parameters of GC/MS analysis. Stainless steel tubes filled with
      Carbograph 5TD were applied successfully for low-volume sampling (2-4 l) with
      minimal breakthrough (< 1%). With the developed method, VVOCs between C3 and C6
      of different volatility and polarity  can be detected even in trace quantities
      with low limits of quantitation (LOQ; 1-3 MUg m-3). Limitations occur for low
      molecular weight compounds <=C3, especially for polar substances, such as
      carboxylic acids and for some aldehydes and alcohols. Consequently, established
      methods for the quantification of these compounds in indoor air cannot be fully
      substituted yet. At least three different analytical techniques are needed to
      cover the large spectrum of relevant VVOCs in indoor air. In addition, unexpected
      reaction products might occur and need to be taken into account to avoid
      misinterpretation of chromatographic signals. Graphical abstract Solid sorbent
      sampling of VVOCs (C3-C6) in indoor air with subsequent TDS-GC/MS analysis.

PMID- 29594430
TI  - Non-targeted analysis of unexpected food contaminants using LC-HRMS.
AB  - A non-target analysis method for unexpected contaminants in food is described.
      Many current methods referred to as "non-target" are capable of detecting
      hundreds or even thousands of contaminants. However, they will typically still
      miss all other possible contaminants. Instead, a metabolomics approach might be
      used to obtain "true non-target" analysis. In the present work, such a method was
      optimized for improved detection capability at low concentrations. The method was
      evaluated using 19 chemically diverse model compounds spiked into milk samples to
      mimic unknown contamination. Other milk samples were used as reference samples.
      All samples were analyzed with UHPLC-TOF-MS (ultra-high-performance liquid
      chromatography time-of-flight mass spectrometry), using reversed-phase
      chromatography and electrospray ionization in positive mode. Data evaluation was
      performed by the software TracMass 2. No target lists of specific compounds were
      used to search for the contaminants. Instead, the software was used to sort out
      all features only occurring in the spiked sample data, i.e., the workflow
      resembled a metabolomics approach. Procedures for chemical identification of
      peaks were outside the scope of the study. Method, study design, and settings in
      the software were optimized to minimize manual evaluation and faulty or
      irrelevant hits and to maximize hit rate of the spiked compounds. A practical
      detection limit was established at 25 MUg/kg. At this concentration, most
      compounds (17 out of 19) were detected as intact precursor ions, as fragments or
      as adducts. Only 2 irrelevant hits, probably natural compounds, were obtained.
      Limitations and possible practical use of the approach are discussed.

PMID- 29594429
TI  - Highly sensitive detection of a small molecule by a paired labels recognition
      system based lateral flow assay.
AB  - Small molecules are difficult to detect by conventional gold lateral flow assay
      (GLFA) sensitively because the test system must satisfy the conflict requirements
      between enough signal intensity and limited antibody (Ab) amount. In this work, a
      paired labels recognition (PLR)-based biosensor was designed by utilizing the
      specific binding of Ab and secondary antibody (anti-Ab) to enhance signal
      intensity and reduce antibody amount applied in small molecule detection. The PLR
      amplification system is fabricated by self-assembling the common detection probe,
      Au-labeled Ab (Au-Ab), and the signal booster, Au-labeled anti-Ab (Au-anti-Ab).
      Benefiting from this, a powerful network structure can be generated to accumulate
      numerous gold nanoparticles (GNPs) and thus significantly strengthen the signal
      intensity of detection. Therefore, a lower Ab amount will be applied to offer
      adequate signal strength, and further, the limit of detection will be obviously
      downregulated due to the more effective competition reaction. Using furazolidone
      (FZD) as a model analyte, we achieve a detection limit of as low as 1 ng mL-1,
      which was at least fivefold improved over that of the traditional GLFA.
      Furthermore, the practicality of this strategy was certificated in five different
      food samples. Graphical abstract A paired labels recognition (PLR) amplification
      system is fabricated by self-assembling the common detection probe, Au-labeled Ab
      (Au-Ab), and the signal booster, Au-labeled anti-Ab (Au-anti-Ab). In this novel
      strategy, owing to the recognition of both Ab and anti-Ab labeled on gold
      nanoparticles (GNPs), a powerful network structure can be generated to accumulate
      numerous GNPs and thus significantly strengthen the signal intensity of
      detection.

PMID- 29594431
TI  - Probiotics for Plants? Growth Promotion by the Entomopathogenic Fungus Beauveria
      bassiana Depends on Nutrient Availability.
AB  - Cultivation of crops requires nutrient supplements which are costly and impact
      the environment. Furthermore, global demands for increased crop production call
      for sustainable solutions to increase yield and utilize resources such as
      nutrients more effectively. Some entomopathogenic fungi are able to promote plant
      growth, but studies over such effects have been conducted under optimal
      conditions where nutrients are abundantly available. We studied the effects of
      Beauveria bassiana (strain GHA) seed treatment on the growth of maize (Zea mays)
      at high and low nutrient conditions during 6 weeks in greenhouse. As expected, B.
      bassiana seed treatment increased plant growth, but only at high nutrient
      conditions. In contrast, the seed treatment did not benefit plant growth at low
      nutrient conditions where the fungus potentially constituted a sink and tended to
      reduce plant growth. The occurrence of endophytic B. bassiana in experimental
      plant tissues was evaluated by PCR after 6 weeks, but B. bassiana was not
      documented in any of the above-ground plant tissues indicating that the fungus
      plant interaction was independent of endophytic establishment. Our results
      suggest that B. bassiana seed treatment could be used as a growth promoter of
      maize when nutrients are abundantly available, while the fungus does not provide
      any growth benefits when nutrients are scarce.

PMID- 29594432
TI  - Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital
      nephrogenic diabetes insipidus.
AB  - : Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the
      reduced ability of renal collecting duct cells to reabsorb water in response to
      the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the
      hallmarks of the disease. Approximately 90% of all patients with CNDI have X
      linked inherited disease caused by variants in the arginine vasopressin receptor
      2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds
      including one or more family members with CNDI. Coding regions of AVPR2 were
      sequenced bi-directionally. We identified eight novel disease-causing variants in
      AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys,
      p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families
      with more than one affected individual, the novel variants segregated with the
      disease. We also identified eight recurrent disease-causing variants, p.Val88Met,
      p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn,
      p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the
      growing list of AVPR2 variants causing X-linked CNDI. CONCLUSION: Being a rapid
      diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in
      newborns with familial predisposition to CNDI. What is Known: * Disease-causing
      variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus
      (CNDI). * DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis,
      early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What
      is New: * We identified eight novel disease-causing variants in AVPR2:
      p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys,
      p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of
      AVPR2 disease-causing variants and emphasizing the importance of genetic testing
      in CNDI.

PMID- 29594433
TI  - The Distributions of Voltage-Gated K+ current Subtypes in Different Cell Sizes
      from Adult Mouse Dorsal Root Ganglia.
AB  - Voltage-gated K+ (KV) currents play a crucial role in regulating pain by
      controlling neuronal excitability, and are divided into transient A-type currents
      (IA) and delayed rectifier currents (IK). The dorsal root ganglion (DRG) neurons
      are heterogeneous and the subtypes of KV currents display different levels in
      distinct cell sizes. To observe correlations of the subtypes of KV currents with
      DRG cell sizes, KV currents were recorded by whole-cell patch clamp in freshly
      isolated mouse DRG neurons. Results showed that IA occupied a high proportion in
      KV currents in medium- and large-diameter DRG neurons, whereas IK possessed a
      larger proportion of KV currents in small-diameter DRG neurons. A lower
      correlation was found between the proportion of IA or IK in KV currents and cell
      sizes. These data suggest that IA channels are mainly expressed in medium and
      large cells and IK channels are predominantly expressed in small cells.

PMID- 29594435
TI  - Higher serum carotenoids associated with improvement of non-alcoholic fatty liver
      disease in adults: a prospective study.
AB  - PURPOSE: Previous studies have suggested that serum carotenoids might be
      inversely associated with non-alcoholic fatty liver disease (NAFLD), but little
      data came from longitudinal studies. We prospectively examined the associations
      between serum-carotenoid levels and NAFLD severity and the intermediary effects
      of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR),
      body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese
      adults. METHODS: This prospective study included 3336 Chinese adults (40-75
      years). We assessed serum concentrations of carotenoids at baseline and
      determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal
      ultrasonography was conducted to assess the presence and degree of NAFLD at years
      3 and 6. RESULTS: The 2687 subjects who completed both NAFLD tests were
      classified into stable, improved and progressed groups according to changes in
      the degree of NAFLD between two visits. Analyses of covariance showed that ln
      transformed serum concentrations of alpha-carotene, beta-cryptoxanthin, beta
      carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively
      associated with NAFLD improvement (all p-trend < 0.05). After multivariable
      adjustment, mean differences in serum carotenoids were higher by 29.6% (beta
      carotene), 18.2% (alpha-carotene), 15.6% (beta-cryptoxanthin), 11.5% (lycopene),
      8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs.
      progressed subjects. Path analyses indicated the carotenoid-NAFLD association was
      mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were
      positively associated with the prevalence and progression of NAFLD. CONCLUSIONS:
      In middle-aged and elderly adults, higher serum-carotenoid concentrations were
      favorably associated with NAFLD improvement, mediated by reducing serum RBP4,
      triglycerides, HOMA-IR, and BMI. TRIAL REGISTRATIONS: This study has been
      registered at http://www.clinicaltrials.gov as NCT03179657.

PMID- 29594436
TI  - A palladium-platinum bimetal nanodendritic melamine network for signal
      amplification in voltammetric sensing of DNA.
AB  - A sandwich-type electrochemical DNA sensor is described for the detection of
      oligonucleotides typical for MECP2 gene mutations. Palladium nanoparticles
      (PdNPs) and platinum nanoparticles (PtNPs) were used to synthesize flower-like
      PdPt nanodendrites (NDs) by a one-pot method. The PdPt NDs possess a high
      specific surface area and excellent catalytic capabilities. They served as the
      carrier for the signal DNA probe (SP) and simultaneously catalyze the reduction
      of hydrogen peroxide (H2O2). The PdPt NDs were modified with melamine, and this
      results in the formation of a PdPt-melamine network through stable interactions
      between the PdPt NDs and the three amino groups of each melamine molecule. The
      network exhibits excellent catalytic ability in enhancing the current signal
      response in the voltammetric detection of MECP2 gene mutation, best measured at 
      0.4 V vs. SCE and using H2O2 as the electrochemical probe. In addition, gold
      nanoflowers were electrodeposited on the electrode interface in order to
      accelerate electron transfer and to capture the capture probe. The sensor is
      stable and can detect MECP2 gene mutations in the 1 fmol.L-1 to 1 nmol.L-1
      concentration range, with a 0.33 fmol.L-1 lower detection limit at an S/N ratio
      of 3. Graphical abstract Schematic presentation of electrodes for the
      determination of the X-linked gene methyl-CpG-binding protein 2 (MECP2). The
      sensor is based on the electrooxidation of added H2O2 by using the melamine
      modified palladium platinum bimetal nanodendrites as network signal amplification
      strategy. This versatile platform expands studies on the detection of monogenic
      disease.

PMID- 29594437
TI  - [Correction to: Endocrine paraneoplastic syndromes].

PMID- 29594439
TI  - Dysplastic megalencephaly phenotype presenting with prenatal high-output cardiac
      failure.
AB  - Dysplastic megalencephaly, also known as bilateral hemimegalencephaly, is a rare
      cerebral malformation characterized by bilateral cerebral hemisphere overgrowth
      and extensive malformation of cortical development. Affected patients present
      clinically with intractable seizures, severe neurological impairment and global
      developmental delay. There is a small body of literature reporting
      megalencephaly's association with neonatal high-output cardiac failure and a lack
      of literature describing prenatal findings. We report a case of dysplastic
      megalencephaly presenting with progressive high-output cardiac failure during
      fetal life. Prenatal and postnatal imaging findings as well as neonatal course
      are described. A companion case with similar imaging findings will help
      illustrate the prenatal imaging characteristics of this association. Knowledge of
      this potential complication related to dysplastic megalencephaly may help guide
      parental counseling and obstetric management.

PMID- 29594438
TI  - [Cardio-renal axis : Relationship of heart failure and renal insufficiency as
      comorbidities].
AB  - Heart failure and kidney dysfunction are common comorbidities with overlapping
      and synergizing mechanisms. Coincidence of both pathologies aggravates disease
      progression rates, symptoms, and outcomes. The treatment of patients with
      advanced renal insufficiency is faced with limited evidence for therapies that
      are standard of care in patients with normal and moderate kidney failure,
      frequent deterioration of kidney function during therapy, and onset of
      hyperkalemia, which pose challenges for clinical care, requiring intensified
      physician-patient contacts. A special challenge is the so-called diuretic
      resistance, which may require extracorporeal drainage.

PMID- 29594440
TI  - Clinical safety of 3-T brain magnetic resonance imaging in newborns.
AB  - BACKGROUND: The effects and potential hazards of brain magnetic resonance imaging
      (MRI) at 3 T in newborns are debated. OBJECTIVE: Assess the impact of 3-T MRI in
      newborns on body temperature and physiological parameters. MATERIAL AND METHODS:
      Forty-nine newborns, born preterm and at term, underwent 3-T brain MRI at term
      corrected age. Rectal and skin temperature, oxygen saturation and heart rate were
      recorded before, during and after the scan. RESULTS: A statistically significant
      increase in skin temperature of 0.6  degrees C was observed at the end of the MRI
      scan (P<0.01). There was no significant changes in rectal temperature, heart rate
      or oxygen saturation. CONCLUSION: Core temperature, heart rate and oxygen
      saturation in newborns were not affected by 3-T brain MR scanning.

PMID- 29594441
TI  - Enhancement of lateral flow immunoassay by alkaline phosphatase: a simple and
      highly sensitive test for potato virus X.
AB  - Alkaline phosphatase (ALP) was used as an amplification tool in lateral flow
      immunoassay (LFIA). Potato virus X (PVX) was selected as a target analyte because
      of its high economic importance. Two conjugates of gold nanoparticles were
      applied, one with mouse monoclonal antibody against PVX and one with ALP-labeled
      antibody against mouse IgG. They were immobilized to two fiberglass membranes on
      the test strip for use in LFIA. After exposure to the sample, a substrate for ALP
      (5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium) was dropped on the
      test strip. The insoluble dark-violet diformazan produced by ALP precipitated on
      the membrane and significantly increased the color intensity of the control and
      test zones. The limit of detection (0.3 ng mL-1) was 27 times lower than that of
      conventional LFIA for both buffer and potato leaf extracts. The ALP-enhanced LFIA
      does not require additional preparation procedures or washing steps and may be
      used by nontrained persons in resource-limited conditions. The new method of
      enhancement is highly promising and may lead to application for routine LFIA in
      different areas. Graphical abstract Two gold nanoparticles (GNP) conjugates were
      used - the first with monoclonal antibodies (mAb) (GNP-mAb); the second -
      alkaline phosphatase-labeled antibody against mAb (GNP-anti-mAb-ALP). The immuno
      complexes are captured by the polyclonal antibodies (pAb) in the test zone.
      Addition of the substrate solution (BCIP/NBT) results in the accumulation of the
      insoluble colored product and in a significance increase in color intensity.

PMID- 29594442
TI  - Determination of bromate via the chemiluminescence generated in the sulfite and
      carbon quantum dot system.
AB  - The authors describe a chemiluminescence (CL)-based assay for the determination
      of bromate. The method is based on the use of a solution of carbon quantum dots
      (CQDs) and sulfite. Strong CL (peak at 490 nm) is observed when bromate is
      injected into the solution. The CL increases linearly in the 0.3 to 10 MUmol L-1
      bromate concentration range, giving a 0.1 MUmol L-1 limit of detection (at an S/N
      ratio of 3). A possible CL mechanism is suggested that involves a redox reaction
      between the CQDs, bromate and sulfite in the acidic medium. This leads to the
      formation of hole-injected and electron-injected CQDs. Radiative recombination of
      oxidant-injected holes and electrons in the CQDs accounts for the occurrence of
      CL. This mechanism contradicts the previous assumption that the transfer of
      energy occurs from SO2* to the CQDs. Although nitrite may interfere in the
      determination of bromate, its effect can be eliminated by adding sulfamic acid.
      The assay is sensitive and represents a new tool for the determination of
      bromate, which is a carcinogen. Graphical abstract Under acidic condition, carbon
      quantum dots (CQDs) can react with sulfite and bromate transforming to hole
      injected CQDs (CQDs*-) and electron-injected CQDs (CQDs*+), respectively.
      Thereafter, strong chemiluminescence (490 nm) aroused from the radiative electron
      hole annihilation between CQDs*- and CQDs*+.

PMID- 29594443
TI  - Fluorescent iridium nanoclusters for selective determination of chromium(VI).
AB  - Fluorescent iridium nanoclusters (IrNCs) consisting of up to 7 Ir atoms were
      prepared by heating IrCl3 in N,N-dimethylformamide. No other reagents are
      required. High resolution transmission electron microscopy (HRTEM) shows the
      IrNCs to be monodispersed with an average size of 0.9 +/- 0.2 nm. They are well
      soluble in polar solvents and stable in these solvents for at least 6 months.
      Under photoexcitation with 365 nm light, they emit strong bluish green
      fluorescence with peaks that depend on the excitation wavelength and range from
      530 to 650 nm. The fluorescence lifetime typically is 2.2 ns and the quantum
      yield is 8.3%. Fluorescence is quenched by Cr(VI) ion (chromate), and the
      emission peak is gradually red-shifted. According to the absorbance spectra of
      IrNCs in the presence and absence of Cr(VI) and Stern-Volmer quenching behavior
      study, static quenching is involved. Based on these findings, a selective assay
      was developed for the determination of Cr(VI). It has a linear response in the
      0.1 to 100 MUM chromate concentration range and a 25 nM detection limit. Graphic
      abstract Fluorescent iridium nanoclusters (IrNCs), consisting of up to 7 Ir
      atoms, were prepared in N,N-dimethylformamide (DMF) solution without using any
      other reagents. Their fluorescence is statically quenched by Cr(VI).

PMID- 29594444
TI  - Epidemiology of hip fractures : Systematic literature review of German data and
      an overview of the international literature.
AB  - BACKGROUND: Hip fractures are regarded as a worldwide epidemic and a major public
      health concern. Changing risk factors, local differences and temporal trends
      contribute to the particular epidemiology of hip fractures. This overview gives a
      comprehensive insight into the epidemiology of hip fractures and reviews where
      German data have contributed to the literature. METHODS: The review of the
      epidemiology of hip fractures in Germany is based on a systematic literature
      search in PubMed. Information about the global epidemiology of hip fractures was
      provided by a selective literature review focusing on specific aspects of the
      epidemiology of hip fractures. RESULTS: Hip fracture rates vary more than 100
      fold between different countries. In most high-income countries, a rise in age
      standardized hip fracture rates was observed until the 1980s and 1990s and a
      decrease thereafter. Such a decrease has not been observed for Germany so far.
      Many factors, diseases and drugs have been found to be associated with hip
      fractures and there is some evidence that fracture risk in later life is already
      programmed during fetal life and early childhood. Of the hip fracture burden 50%
      occur in people with disability and in need of care. In nursing homes
      approximately 4 fractures can be expected in 100 women per year. In people with
      intellectual or developmental disabilities comparable risks of hip fracture occur
      10-40 years earlier than in the general population. Incidence of disability,
      institutionalization and death are frequent consequences of hip fractures.
      CONCLUSION: The epidemiology of hip fractures is characterized by a high burden
      of disease, local differences, temporal trends, well-defined high-risk
      populations and many established risk factors.

PMID- 29594445
TI  - The prognostic implications of primary tumor location on recurrence in early
      stage colorectal cancer with no associated risk factors.
AB  - PURPOSE: Recently, several reports have suggested that tumor location serves as a
      prognostic biomarker in advanced colorectal cancer. However, the prognostic
      implication of tumor location in patients with early-stage colorectal cancer
      remains unclear. This study was aimed to examine the prognostic implication of
      tumor location in patients with early-stage colorectal cancer. METHODS: Patients
      with stage I and low-risk stage II colorectal cancer, treated with radical
      surgery in a hospital setting between May 2003 and September 2014, were
      retrospectively reviewed. Patients who underwent (neo) adjuvant chemotherapy
      and/or radiotherapy and whose microsatellite instability (MSI) status was lacked
      were excluded. Distal colon cancer was defined as tumors located from the splenic
      flexure colon to the sigmoid colon. RESULTS: A total of 712 patients were
      included in this study. Of these patients, 23 (3.2%) had a recurrence at a median
      follow-up time of 46 months. The tumor recurrence rate was significantly low in
      patients with proximal colon cancer. In the multivariate analysis, tumors located
      in the distal colon or rectum (distal colon, hazard ratio [HR] 9.213, P = 0.035;
      rectum, HR 15.366, P = 0.009) and T3 tumors (HR 4.590, P = 0.017) were related to
      tumor recurrence. A higher prevalence of tumor recurrence was found in patients
      with two recurrence factors than those who had only one factor or none (P <
      0.001). CONCLUSIONS: Tumor location, as well as T stage, had prognostic
      implication in patients with early-stage colorectal cancer. Validation of our
      results is needed in a large cohort with genetic characterization.

PMID- 29594446
TI  - Comprehensive Evaluation of Soil Near Uranium Tailings, Beishan City, China.
AB  - To evaluate the impact of uranium tailings on soil composition and soil
      microbial, six soil samples at different distance from the uranium tailings
      (Beishan City, China) were collected for further analysis. Concentrations of
      radionuclides (238U and 232Th), heavy metals (Mn, Cd, Cr, Ni, Zn, and Pb) and
      organochlorine pesticide were determined by ICP-MS and GC, they were
      significantly higher than those of the control. And the Average Well Color
      Development as well as the Shannon, the Evenness, and the Simpson index were
      calculated to evaluate the soil microbial diversity. The carbon utilization model
      of soil microbial community was also analyzed by Biolog-eco. All results
      indicated that uranium tailings leaded to excessive radionuclides and heavy
      metals, and decreased the diversity of the soil microbial community. Our study
      will provide a valuable basis for soil quality evaluation around uranium tailing
      repositories and lay a foundation for the management and recovery of uranium
      tailings.

PMID- 29594447
TI  - A conventional chemical reaction for use in an unconventional assay: A
      colorimetric immunoassay for aflatoxin B1 by using enzyme-responsive just-in-time
      generation of a MnO2 based nanocatalyst.
AB  - The authors describe a colorimetric immunoassay for the model nalyte aflatoxin B1
      (AFB1). It is based on the just-in-time generation of an MnO2 nanocatalyst.
      Unlike previously developed immunoassay, the chromogenic reaction relies on the
      just-in-time formation of an oxidase mimic without the aid of the substrate.
      Potassium permanganate (KMnO4) is converted into manganese dioxide (MnO2) which
      acts as an oxidase mimic that catalyzes the oxidation 3,3',5,5'
      tetramethylbenzidine (TMB) by oxygen to give a blue colored product. In the
      presence of ascorbic acid (AA), KMnO4 is reduced to Mn(II) ions. This results in
      a decrease in the amount of MnO2 nanocatalyst. Hence, the oxidation of TMB does
      not take place. By adding ascorbate oxidase, AA is converted into dehydroascorbic
      acid which cannot reduce KMnO4. Based on these observations, a colorimetric
      competitive enzyme immunoassay was developed where ascorbate oxidase and gold
      nanoparticle-labeled antibody against AFB1 and magnetic beads carrying bovine
      serum albumin conjugated to AFB1 are used for the determination of AFB1. In
      presence of AFB1, it will compete with the BSA-conjugated AFB1 (on the magnetic
      beads) for the labeled antibody against AFB1 on the gold nanoparticles. This
      makes the amount of ascorbate oxidase/anti-AFB1 antibody-labeled gold
      nanoparticles, which conjugated on magnetic beads, reduce, and resulted in an
      increase of ascorbic acid. Under optimal conditions, the absorbance (measured at
      652 nm) decreases with increasing AFB1 concentrations in the range from 0.1 to
      100 ng mL-1, with a 0.1 ng mL-1 detection limit (at the 3Sblank level). The
      accuracy of the assay was validated by analyzing spiked peanut samples. The
      results matched well with those obtained with a commercial ELISA kit.
      Conceivably, the method is not limited to aflatoxins but has a wide scope in that
      it may be applied to many other analytes for which respective antibodies are
      available. Graphical abstract Schematic illustration of ascorbate oxidase (AOx)
      mediated potassium permanganate (KMnO4)-responsive ascorbic acid (AA) for visual
      colorimetric immunoassay of aflatoxin B1 (AFB1) by coupling with hydrolytic
      reaction of AOx toward AA and the KMnO4-Mn(II)-TMB system [note: 3,3',5,5'
      tetramethylbenzidine: TMB].

PMID- 29594448
TI  - A multimodal impedimetric sensor for humidity and mechanical pressure using a
      nanosized SnO2-Mn3O4 mixed oxide.
AB  - The authors describe a sensor based on the deposition of the binary oxide SnO2
      Mn3O4 between copper electrodes fixed on a glass substrate. The impedance of the
      sensor is shown to strongly depend on relative humidity (RH) and mechanical
      pressure. A silicone adhesive was added to the binary oxide nanomaterials and
      investigated with respect to its effect on the sensing performance. The impedance
      of the material decreases by a factor of 54.7 with increasing RH in the range of
      10-90% in pristine SnO2-Mn3O4 nanorods, but 29.6 times in SnO2-Mn3O4
      nanocomposites. Capacitance increases 390 times in pristine SnO2-Mn3O4 and 26.6
      times in SnO2-Mn3O4 silicone nanocomposite at 100 Hz on going from 10 to 90% RH.
      Similarly, the impedance of the sensor also depends on mechanical pressure. The
      impedance of the material decreases by 80% on applying a mechanical pressure of
      11.0 kN.m-2, while capacitance increases by 70% at the same pressure. Graphical
      abstract A multimodal sensor was fabricated using SnO2-Mn3O4 mixed oxide and its
      nanocomposite with silicon adhesive. The impedance of the material decreases
      while capacitance increases much more with increase in relative humidity and
      applying a mechanical pressure in SnO2-Mn3O4 mixed oxide as compared to SnO2
      Mn3O4 nanocomposite.

PMID- 29594450
TI  - Determination of the activity of alkaline phosphatase by using nanoclusters
      composed of flower-like cobalt oxyhydroxide and copper nanoclusters as
      fluorescent probes.
AB  - The authors describe a sensitive fluorometric method for the determination of the
      activity of alkaline phosphatase (ALP). It is based on the use of a composite
      prepared consisting of flower-like cobalt oxyhydroxide (CoOOH) and copper
      nanoclusters (CuNCs). On formation of the CuNC-CoOOH aggregates, the fluorescence
      of the CuNCs is quenched by the CoOOH sheets. If, however, the CoOOH sheets are
      reduced to Co(II) ions in the presence of ascorbic acid (AA), fluorescence
      recovers. AA is formed in-situ by hydrolysis of the substrate ascorbic acid 2
      phosphate (AA2P) as catalyzed by ALP. Thus, the ALP activity can be detected
      indirectly by kinetic monitoring of the increase in fluorescence, best at
      excitation/emission wavelengths of 335/410 nm. The assay allows ALP to be
      determined in 0.5 to 150 mU.mL-1 activity range and with a 0.1 mU.mL-1 detection
      limit. The method was successfully applied to the determination of ALP activity
      in (spiked) human serum samples. The assay has attractive features in being of
      the off-on type and immune against false positive results. Graphical Abstract A
      fluorescent bioassay is reported for the determination of the activity of
      alkaline phosphatase (ALP). It is exploiting the ascorbic acid (AA)-induced
      decomposition of nanoclusters composed of flower-like cobalt oxyhydroxide and
      copper nanoclusters. ALP catalyzes hydrolysis of ascorbic acid 2-phosphate (AA2P)
      and dephosphorylation to form AA.

PMID- 29594451
TI  - A nanocomposite prepared from a polypyrrole deep eutectic solvent and coated onto
      the inner surface of a steel capillary for electrochemically controlled
      microextraction of acidic drugs such as losartan.
AB  - The authors describe a new coating for use in electrochemically controlled in
      tube solid phase microextraction (EC-IT-SPME). It consists of a nanocomposite
      that was prepared from polypyrrole and deep eutectic solvent (DES) by
      electrochemical deposition on the inner walls of a stainless steel capillary that
      serves as a working electrode. The hypertension drug losartan acts as an acidic
      model analyte. The extraction efficiency, mechanical stability, chemical
      stability and lifetime of the coating were investigated. It is found to be quite
      stable in relatively acidic and basic media and to be re-usable >450 times
      without decrease in extraction efficiency. Its extraction capability in
      comparison to the commercial polypyrrole coating is better by a factor of 1.5.
      The coated steel capillary was used as the anode (anion-exchanger), and a
      platinum electrode was used as the cathode. By passing a sample solution through
      the electrode, losartan can be extracted by applying a positive potential to the
      flow. In the next step, losartan is electrochemically desorbed and subjected to
      HPLC analysis with UV detection. Under optimal conditions, losartan can be
      quantified with limits of detection that range from 50 to 500 ng L-1 depending on
      the sample matrix. Response is linear in the 0.1-500 MUg L-1 concentration range.
      The inter- and intra-assay precisions (RSDs; in %, for n = 3) are in the range
      from 2.4-4.6% and from 1.9-3.9%, respectively. Graphical abstract Schematic of
      the preparation of a nano-structured polypyrrole-deep eutectic solvent
      nanocomposite coating placed on the inner surface of a stainless steel capillary
      and used for electrochemically controlled in-tube solid phase microextraction of
      losartan from biological samples.

PMID- 29594449
TI  - Nanoparticle assisted laser desorption/ionization mass spectrometry for small
      molecule analytes.
AB  - Nanoparticle assisted laser desorption/ionization mass spectrometry (NPs-ALDI-MS)
      shows remarkable characteristics and has a promising future in terms of real
      sample analysis. The incorporation of NPs can advance several methods including
      surface assisted LDI-MS, and surface enhanced LDI-MS. These methods have advanced
      the detection of many thermally labile and nonvolatile biomolecules.
      Nanoparticles circumvent the drawbacks of conventional organic matrices for the
      analysis of small molecules. In most cases, NPs offer a clear background without
      interfering peaks, absence of fragmentation of thermally labile molecules, and
      allow the ionization of species with weak noncovalent interactions. Furthermore,
      an enhancement in sensitivity and selectivity can be achieved. NPs enable
      straightforward analysis of target species in a complex sample. This review (with
      239 refs.) covers the progress made in laser-based mass spectrometry in
      combination with the use of metallic NPs (such as AuNPs, AgNPs, PtNPs, and
      PdNPs), NPs consisting of oxides and chalcogenides, silicon-based NPs, carbon
      based nanomaterials, quantum dots, and metal-organic frameworks. Graphical
      abstract An overview is given on nanomaterials for use in surface-assisted laser
      desorption/ionization mass spectrometry of small molecules.

PMID- 29594452
TI  - Lysozyme aptasensor based on a glassy carbon electrode modified with a
      nanocomposite consisting of multi-walled carbon nanotubes, poly(diallyl dimethyl
      ammonium chloride) and carbon quantum dots.
AB  - An aptamer-based method is described for electrochemical determination of
      lysozyme. A glassy carbon electrode was modified with a nanocomposite composed of
      multi-walled carbon nanotubes, poly(diallyl dimethyl ammonium chloride), and
      carbon quantum dots. The composition of the nanocomposite (MWCNT/PDDA/CQD)
      warrants good electrical conductivity and a high surface-to-volume ratio. The
      lysozyme-binding aptamers were immobilized on the nanocomposite via covalent
      coupling between the amino groups of the aptamer and the carboxy groups of the
      nanocomposite. The modified electrode was characterized by electrochemical
      impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry.
      The use of this nanocomposite results in a considerable enhancement of the
      electrochemical signal and contributes to improving sensitivity. Hexacyanoferrate
      was used as an electrochemical probe to study the dependence of the peak current
      on lysozyme concentration. In the presence of lysozyme, the interaction of
      lysozyme with immobilized aptamer results in a decrease of the peak current, best
      measured at +0.15 V vs. Ag/AgCl. A plot of peak current changes versus the
      logarithm of the lysozyme concentration is linear in the 50 fmol L-1 to 10 nmol L
      1 concentration range, with a 12.9 fmol L-1 detection limit (at an S/N ratio of
      3). The method is highly reproducible, specific and sensitive, and the electrode
      has a rapid response. It was applied to the determination of lysozyme in egg
      white, serum, and urine. Graphical abstract Schematic of a nanocomposite composed
      of multi-walled carbon nanotubes (MWCNTs), poly(diallyldimethyl ammonium
      chloride) (PDDA), and carbon quantum dots (CQDs) for use in a lysozyme
      aptasensor. The aptamer was immobilized on the surface, and bovine serum albumin
      (BSA) was applied to block the surface. The changes of peak current for the
      electrochemical probe hexacyanoferrate (Fe(CN)63-/4-) in the presence and absence
      of lysozyme was traced.

PMID- 29594453
TI  - Determination of trace uric acid in serum using porous graphitic carbon nitride
      (g-C3N4) as a fluorescent probe.
AB  - Porous graphitic carbon nitride (g-C3N4) was prepared by a one-step acid etching
      and ultrasonication process. It is found that the strong blue fluorescence of g
      C3N4 (with excitation/emission maxima at 320/400 nm) is fairly selectively
      quenched by uric acid (UA). The morphology and chemical structure of the
      nanoporous g-C3N4 were characterized by XRD, TEM and FTIR. Quenching studies and
      Stern-Volmer plots reveal two UA concentration ranges of different quenching
      efficiency. The first extends from 50 to 500 nM, the other from 0.5 to 10 MUM.
      The limit of detection is 8.4 nM. The two quenching processes are attributed to
      both dynamic and static quenching. The porous g-C3N4 probes were applied to the
      determination of UA in (spiked) human serum and human plasma, and the results
      were as good as those obtained with UA standard solutions. These data illustrate
      that g-C3N4 can be used to selectively and sensitively quantify trace levels of
      UA even in a complex environment. Graphical abstract Porous graphite nitride
      carbon (g-C3N4) is shown to be a viable fluorescent probe for uric acid (UA) via
      both dynamic and static quenching. The electron transfer of carbon nitride is
      represented by the arrows; hnu is the incident light; PL is the fluorescence
      emission.

PMID- 29594454
TI  - Cyclodextrin-modified nanodiamond for the sensitive fluorometric determination of
      doxorubicin in urine based on its differential affinity towards beta/gamma
      cyclodextrins.
AB  - The manuscript reports on the preparation of beta-cyclodextrin-modified
      nanodiamonds (betaCD-ND) for the extraction and preconcentration of the
      fluorescent anticancer drug doxorubicin (DOX) from biological samples. The
      inclusion of DOX into the cavities of beta- and gamma-cyclodextrin (CD) confirms
      their utility for selective extraction and elution of the drug based on its good
      fit to the cyclodextrin cavity. Although both larger cyclodextrins (betaCD and
      gammaCD) accommodate DOX, DOX clearly prefers the bigger gammaCD cavities.
      Dispersive micro solid-phase extraction using betaCD-ND as sorbent enables the
      inclusion complexation of DOX. The elution of DOX from betaCD-ND cavities occurs
      with a basic solution of gammaCD containing 10% acetonitrile owing to the
      preferential affinity (i.e. optimal fit) of DOX into the larger gammaCD cavity.
      DOX is quantified by monitoring its intrinsic fluorescence (exc/em = 475/595 nm).
      The method can determine DOX in urine with a limit of detection of 18 ng.mL-1.
      Recoveries (93.2% and 94.0%) and precision (RSDs of 5.9% and 4.7%) at 100 and 400
      ng.mL-1 DOX levels in urine are satisfactory. The matrix effect is negligible
      even when working with undiluted urine samples. Graphical abstract Nanodiamonds
      functionalized with beta-cyclodextrin (betaCD-ND) were used as sorbent for the
      determination of nanomolar levels of doxorubicin (DOX). It is based on host:guest
      interactions ruled by different stabilities of DOX within cyclodextrin (CD)
      cavity-size: betaCD/gammaCD.

PMID- 29594455
TI  - Strong enhancement of the chemiluminescence of the Cu(II)-H2O2 system on addition
      of carbon nitride quantum dots, and its application to the detection of H2O2 and
      glucose.
AB  - The authors report that carbon nitride quantum dots (CN QDs) exert a strong
      enhancing effect on the Cu(II)/H2O2 chemiluminescent system. Chemiluminescence
      (CL) intensity is enhanced by CN QDs by a factor of ~75, while other carbon
      nanomaterials have a much weaker effect. The possible mechanism of the effect was
      evaluated by recording fluorescence and CL spectra and by examining the effect of
      various radical scavengers. Emitting species was found to be excited-state CN QDs
      that produce green CL peaking at 515 nm. The new CL system was applied to the
      sensitive detection of H2O2 and glucose (via glucose oxidase-catalyzed formation
      of H2O2) with detection limits (3sigma) of 10 nM for H2O2 and 100 nM for glucose.
      The probe was employed for glucose determination in human plasma samples with
      satisfactory results. Graphical abstract The effect of carbon nitride quantum
      dots (CN QDs) on Cu(II)-H2O2 chemiluminescence reaction was studied and the new
      CL system was applied for sensitive detection of glucose based on the glucose
      oxidase (GOx)-catalyzed formation of H2O2.

PMID- 29594456
TI  - Combined pharmacotherapy for osteonecrosis of the femoral head after severe acute
      respiratory syndrome and interstitial pneumonia: two and a half to fourteen year
      follow-up.
AB  - PURPOSE: The purpose of this study was to retrospectively analyze the clinical,
      functional, and radiological outcomes of combined pharmacotherapy to ONFH after
      high-dose corticosteroid therapy. METHOD: From August 2003 to June 2015, five
      patients (ten hips) of ONFH in ARCO stage I, after SARS and Interstitial
      pneumonia, were treated by combined pharmacotherapy. Lipo-prostaglandin E1 10 MUg
      iv Bid * 28 days, enoxaparin 6000 iu H QD * 12 weeks, alendronate sodium tablet
      10 mg QD * 1 year. The patients were fully weight-bearing following completion of
      the follow-up. RESULT: For these five patients (ten hips), Harris score was 100
      from the diagnosis to final follow-up time. Radiologic findings show no signs of
      collapse, necrotic focus was repaired, and ARCO stages were changed from IC into
      IIB. CONCLUSION: This combined pharmacotherapy has promising treatment results
      for delaying or preventing collapse of ONFH in ARCO stage I.

PMID- 29594457
TI  - Micro-solid phase extraction of chlorophenols using reduced graphene oxide
      functionalized with magnetic nanoparticles and graphitic carbon nitride as the
      adsorbent.
AB  - A magnetic micro-solid phase extraction method was applied for the extraction of
      trace levels of various chlorophenols prior to their determination by high
      performance liquid chromatography. The reduced graphene oxide functionalized with
      magnetic iron oxide nanoparticles and graphitic carbon nitride was prepared and
      used as adsorbent. It was characterized by scanning electron microscope, X-ray
      diffraction and vibrating sample magnetometer. Placed in a polypropylene hollow
      tube, the material was applied to the extraction of 3-chlorophenol, 2,3
      dichlorophenol, 2,4-dichlorophenol, and 2,4,6-trichlorophenol in cosmetic
      samples. Several experimental parameters that affect extraction efficiency were
      optimized. Following desorption with alkaline methanol, the chlorophenols were
      quantified by high performance liquid chromatography. A linear response was
      observed in the 1.0-200 MUg.kg-1 CP concentration ranges. The detection limits
      (at a signal-to-noise ratio of 3) are between 0.20 and 0.30 MUg.kg-1. The
      relative recoveries of the CPs from spiked cosmetics samples were in the range
      from 80.5 to 104%, with relative standard deviations lower than 12%. The filled
      extraction tube is high durable and stable. It can be used for 120 extraction
      cycles without a significant loss of extraction efficiency. The good adsorption
      ability of the sorbent was attributed to the strong pi stacking interaction
      between the graphitic carbon nitride functionalized reduced graphene oxide and
      the aromatic rings in the CPs. Graphical abstract A magnetic micro-solid phase
      extraction (M-MUSPE) method was applied to the extraction of various trace
      chlorophenols prior to their determination by high performance liquid
      chromatography. The M-MUSPE method combines the advantages of both MSPE and
      MUSPE.

PMID- 29594459
TI  - Iron storage disease (hemochromatosis) and hepcidin response to iron load in two
      species of pteropodid fruit bats relative to the common vampire bat.
AB  - Hepcidin is the key regulator of iron homeostasis in the body. Iron storage
      disease (hemochromatosis) is a frequent cause of liver disease and mortality in
      captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this
      condition are unknown. Hereditary hemochromatosis in humans is due to deficiency
      of hepcidin or resistance to the action of hepcidin. Here, we investigated the
      role of hepcidin in iron metabolism in one species of pteropodid bat that is
      prone to iron storage disease [Egyptian fruit bat (with and without
      hemochromatosis)], one species of pteropodid bat where iron storage disease is
      rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a
      natural diet very high in iron, in which iron storage disease is not reported
      [common vampire bat (Desmodus rotundus)]. Iron challenge via intramuscular
      injection of iron dextran resulted in significantly increased liver iron content
      and histologic iron scores in all three species, and increased plasma iron in
      Egyptian fruit bats and straw-colored fruit bats. Hepcidin mRNA expression
      increased in response to iron administration in healthy Egyptian fruit bats and
      common vampire bats, but not in straw-colored fruit bats or Egyptian fruit bats
      with hemochromatosis. Hepcidin gene expression significantly correlated with
      liver iron content in Egyptian fruit bats and common vampire bats, and with
      transferrin saturation and plasma ferritin concentration in Egyptian fruit bats.
      Induction of hepcidin gene expression in response to iron challenge is absent in
      straw-colored fruit bats and in Egyptian fruit bats with hemochromatosis and,
      relative to common vampire bats and healthy humans, is low in Egyptain fruit bats
      without hemochromatosis. Limited hepcidin response to iron challenge may
      contribute to the increased susceptibility of Egyptian fruit bats to iron storage
      disease.

PMID- 29594458
TI  - Host genetics in malaria: lessons from mouse studies.
AB  - Malaria remains a deadly parasitic disease caused by Plasmodium, claiming almost
      half a million lives every year. While parasite genetics and biology are often
      the major targets in many studies, it is becoming more evident that host genetics
      plays a crucial role in the outcome of the infection. Similarly, Plasmodium
      infections in mice also rely heavily on the genetic background of the mice, and
      often correlate with observations in human studies, due to their high genetic
      homology with humans. As such, murine models of malaria are a useful tool for
      understanding host responses during Plasmodium infections, as well as dissecting
      host-parasite interactions through various genetic manipulation techniques.
      Reverse genetic approach such as quantitative trait loci studies and random
      mutagenesis screens have been employed to discover novel host genes that affect
      malaria susceptibility in mouse models, while other targeted studies utilize
      mouse models to validate observation from human studies. Herein, we review the
      findings from the past and present studies on murine models of hepatic and
      erythrocytic stages of malaria and speculate on how the current mouse models
      benefit from the recent development in CRISPR/Cas9 gene editing technology.

PMID- 29594460
TI  - Does endoscopic puncture of ureterocele provide not only an initial solution, but
      also a definitive treatment in all children? Over the 26 years of experience.
AB  - PURPOSE: We have retrospectively evaluated all patients who underwent endoscopic
      puncture (EP) of ureterocele over the last 26 years with special reference to the
      need in the second intervention and disease-free status. METHODS: 78 (69%) of the
      112 patients following EP and completed follow-up were included. 51 (65%) were
      diagnosed prenatally and 27 (35%) postnatally. 46 patients (60%) had
      intravesical, while 32 (40%) had ectopic ureterocele. Median age at time of
      puncture was 4 months. Median time of the follow-up was 12 years (range 1-26
      years), while 23 (30%) followed over 10 years and 15 (19%) completed adolescent
      period. RESULTS: Four children with ectopic ureterocele required secondary
      puncture. Ectopic ureterocele children had significantly more postoperative UTIs
      (13 (40%) ectopic vs 4 (19%) intravesical p = 0.047). 19 RRUs (44%) showed
      spontaneous resolution of VUR. 14 (18%) children required additional surgery: 7,
      endoscopic correction of VUR; 3, ureteral reimplantation and 4, partial
      nephrectomy. The need for additional surgery following puncture was higher in the
      group of children with ectopic ureterocele; however, this difference did not
      reach a statistical significance (p = 0.716). CONCLUSIONS: Our data show that EP
      of ureterocele is a durable and long-term effective procedure in vast majority of
      the children.

PMID- 29594461
TI  - Impact of surgery, adjuvant treatment, and other prognostic factors in the
      management of anaplastic ganglioglioma.
AB  - BACKGROUND/PURPOSE: Anaplastic ganglioglioma (AGG) is a rare tumor with both
      glial and neuronal component accounting for less than 1% of all CNS tumors with
      limited information about the optimum treatment and outcome of these tumors.
      METHOD AND MATERIALS: We did a thorough search of the PubMed with the following
      MesH terms: "Ganglioglioma; Anaplastic ganglioglioma; Ganglioglioma AND
      treatment; and Anaplastic ganglioglioma AND survival" to find all possible
      publications related to AGG to perform an individual patient data analysis and
      derive the survival outcome and optimum treatment of these tumors. RESULTS: A
      total of 56 articles were retrieved pertaining to AGG with 88 patients. However,
      a total of 40 publications found eligible with 69 patients for individual patient
      data analysis. Median age for the entire cohort was 16 years (range 0.2-77
      years). Surgical details were available for 64 patients. A gross total or near
      total resection was reported in 21 cases (32.8%), subtotal resection or debulking
      was reported in 25 cases (39.1%). Surgical details were available for 64
      patients. A gross total or near total resection was reported in 21 cases (32.8%),
      and subtotal resection or debulking was reported in 25 cases (39.1%). Median
      overall survival (OS) was 29 months [95% CI 15.8-42.2 months] with 2- and 5-year
      OS 61 and 39.4% respectively. CONCLUSION: AGG is associated with a dismal.
      Pediatric age and a gross total resection of tumor confer a better progression
      free survival and OS. Hence, surgery should remain the cornerstone of therapy.
      However, because of modest survival, there is enough opportunity to improve
      survival with addition of adjuvant radiation and chemotherapy. A whole genome
      sequencing and molecular characterization would help to derive the best treatment
      option.

PMID- 29594462
TI  - Placode rotation in transitional lumbosacral lipomas: are there implications for
      origin and mechanism of deterioration?
AB  - PURPOSE: Rotation of the lipoma-neural placode has been noted in transitional
      lumbosacral lipomas. The purpose of this study was to confirm this rotation; that
      this rotation occurs with a preference to the left, and correlates with clinical
      symptoms. In addition, this study tests the hypothesis that this rotation occurs
      through local mechanical forces rather than intrinsic congenital malformation.
      METHODS: Lipomas were classified as per the Chapman classification. Degree of
      rotation of the placode from the coronal plane was recorded along with the
      presence of herniation outside of the vertebral canal. Abnormalities on
      urodynamic testing were recorded, along with neuro-orthopaedic signs picked up on
      formal neuro-physiotherapy assessment. RESULTS: Placode rotation occurs more
      frequently in the transitional group. Regardless of lipoma classification,
      rotation was much more common to the left. Furthermore, when lateralisation of
      symptoms was present, this strongly correlated with the direct of rotation. There
      was no difference in rotation of the placode whether it was within
      (lipomyelocoele) or without the vertebral canal (lipomyelomeningocoele).
      CONCLUSIONS: Placode rotation is a feature of transitional lumbosacral lipomas
      and may account for the increase in symptoms amongst this subgroup. Herniation of
      the placode outside the vertebral canal does not increase the risk of rotation
      suggesting a congenital cause for this finding rather than a purely mechanical
      explanation.

PMID- 29594463
TI  - Traumatic brain injury in Indian children.
AB  - INTRODUCTION: Traumatic brain injury (TBI) in children and adolescents is a
      community-based medical and educational challenge world-over due to increasing
      urbanization and motorization. In India, children between 1 to 15 years
      constitute significant proportion of the total population, who are vulnerable for
      TBI. In developed countries, pediatric trauma mortality still represents more
      than half of all childhood fatalities, which is 18 times more common than brain
      tumors. In this study, we attempted to analyze epidemiological factors,
      management, and outcome of TBI in children at a tertiary care center in Pune,
      Maharashtra. AIM AND OBJECTIVES: To study the clinical spectrum of pediatric
      traumatic brain injury cases received at a Tertiary Care Hospital. MATERIALS AND
      METHODS: This prospective study (August 2015-July 2017), conducted at our
      institution, includes all children < 16 years with TBI reporting to the
      neurosurgical emergency department. All the case records were reviewed and the
      pertinent data (clinical history, age, sex, mode of injury, computed tomography
      (CT) scan findings, interventions, morbidity, and mortality) analyzed. Any
      residual neurological deficits at the time discharge were assessed as the outcome
      of TBI. RESULTS: A total 76 pediatric cases of TBI were admitted during the
      period of August 2015-July 2017, with 51 males (67%) and 25 females (33%) with
      male to female ratio 2:1. Mean age of incidence in our study is 5.5 years. Out of
      76 children with TBI, 60.5% were of mild, 14.5% moderate, and 25% severe TBI.
      Overall, RTA (40.8%) is the most common mode of injury followed by fall from
      height (30.2%) and slippage in and around home (26.4%). Clinical evaluation
      revealed, loss of consciousness(LOC) in 36 (47.3%) patients, vomiting in 42 (55%)
      patients, headache in 10 (13%) patients, ENT bleeding in 18 (23.6%), and seizure
      in 16 (21%) patients, no external injuries in 25 (33%) patients, normal sensorium
      was found in 41 (54%) patients, 18 (23.6%) children were drowsy at presentation,
      and 17 (22.3%) children were unconscious. CT scan findings revealed no gross
      abnormality in (26%), extradural heamorrhage (EDH) (18.4%), subdural hemorrhage
      (SDH) (14.4%), subarachnoid hemorrhage (21%), fracture skull (55.26%), cerebral
      oedema, and contusion (48.68%) as the radiological injury patterns. Out of 76
      children, 42 (55%) children are managed with only observation, 26 (34%) children
      required only medical pharmacological treatment, and 8 (10.5%) children required
      surgical intervention, 24, (31.6%) children required mechanical ventilation.
      Overall mortality is 5.26%. Thus among the survivors (n = 72), 57 (79%) went home
      with no residual deficit, 3 (4%) had headache, 4 (5.5%) had hemiparesis, 2 (2.7%)
      had monoparesis, 1 (1.4%) had hypertonia, 3 (4%) had seizures, 2 (2.7%) had
      hydrocephalus, 2 (2.7%) had facial palsy, 2 (2.7%) had vision impairment, and 2
      (2.7%) had speech impairment. In our study, we found that there is a significant
      association between residual deficits and severity of injury (p = 0.3), there is
      no significant association between mode of injury and outcome (p = 0.7). Mean
      duration of stay in hospital was 6.9 days but 60% of patients had stay of less
      than 5 days. CONCLUSION: Most of these injuries are preventable in infancy and
      childhood by ensuring proper vigilance, tender care by the parents and the
      caretakers. Safe driving techniques have to be followed by parents while
      traveling with children in their motor vehicles. Need to focus on grading the
      severity of TBI rather than on factors like age, mode of injury, and presence or
      absence of external injuries.

PMID- 29594465
TI  - Interpreting body MRI cases: classic findings in abdominal MRI.
AB  - Few things in radiology are "pathognomonic" in their appearance or presentation.
      However, having an awareness of those findings which are specific to a certain
      entity is important when interpreting imaging studies. These classic findings can
      be identified with many imaging modalities, but no modality provides as many
      recognizable observations as an MRI. This results from the large variety of pulse
      sequences that provide high contrast resolution, prior to and following contrast
      administration. In this article, the most classically recognized abdominal
      findings are presented including the following: Liver: Cyst, hemangioma, focal
      nodular hyperplasia, hepatic adenoma, hemosiderosis, hepatocellular carcinoma.
      Spleen: Cyst, hemangioma, lymphangioma, hemosiderosis, Gandy-Gamna bodies.
      Biliary system: Biliary stones and choledocholithiasis, pneumobilia, choledochal
      cyst. Gallbladder: Adenomyomatosis, sludge, surgical clips in the gallbladder
      fossa. Pancreas: Pancreatic divisum, intraductal papillary mucinous neoplasm,
      pseudocyst, autoimmune pancreatitis, chronic pancreatitis, adenocarcinoma.
      Kidneys: Simple cyst, hemorrhagic cyst, renal sinus cyst, angiomyolipoma, solid
      mass.

PMID- 29594464
TI  - Heavy metal tolerance in marine strains of Yarrowia lipolytica.
AB  - Heavy metal tolerance of two marine strains of Yarrowia lipolytica was tested on
      solid yeast extract peptone dextrose agar plates. Based on minimum inhibitory
      concentration esteems, it is inferred that the two strains of Y. lipolytica were
      tolerant to heavy metals such as Pb(II), Cr(III), Zn(II), Cu(II), As(V), and
      Ni(II) ions. The impact of various heavy metal concentrations on the growth
      kinetics of Y. lipolytica was likewise assessed. With increased heavy metal
      concentration, the specific growth rate was reduced with delayed doubling time.
      Furthermore, biofilm development of both yeasts on the glass surfaces and in
      microtitre plates was assessed in presence of different heavy metals. In
      microtitre plates, a short lag phase of biofilm formation was noticed without the
      addition of heavy metals in yeast nitrogen base liquid media. A lag phase was
      extended over increasing metal concentrations of media. Heavy metals like Cr(VI),
      Cd(II), and As(V) are contrastingly influenced on biofilms' formation of
      microtitre plates. Other heavy metals did not much influence on biofilms
      development. Thus, biofilm formation is a strategy of Y. lipolytica under stress
      of heavy metals has significance in bioremediation process for recovery of heavy
      metals from contaminated environment.

PMID- 29594466
TI  - Outcome of liver lesions indeterminate for malignancy on ultrasound: the role of
      patient age, risk status, and lesion echogenicity.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between final
      outcome of lesions indeterminate for malignancy on ultrasound (US) and patient
      and imaging characteristics. METHODS: We identified all patients with
      indeterminate liver lesions on US between 9/1/2013 and 12/31/2014 using
      institutional codes based on radiologist opinion. Miscoded lesions (n = 30) and
      patients with no imaging, pathology, or clinical follow-up at our health system
      (n = 6) were excluded. Final diagnostic category of malignant, benign,
      pseudolesion, or indeterminate was assigned using imaging, pathology, and
      clinical follow-up. Differences in diagnostic categories were compared by patient
      (age, gender, race, known malignancy. or liver disease) and imaging
      characteristics (lesion size, echogenicity. and number). Independent likelihood
      of a benign final diagnostic category was adjusted for significant variables on
      univariate analysis. RESULTS: Indeterminate liver lesions on US were found in
      153/6813 patients (2%). Final diagnostic categories were malignant (11/153, 7%),
      benign (94/153, 61%), pseudolesion (42/153, 27%). and indeterminate (6/153, 4%).
      Nearly one-third of hypoechoic masses in patients with known malignancy or liver
      disease (i.e., high-risk status) >= 46 years of age were malignant (9/28, 32%).
      On multivariate analysis, patients of age >= 61 years and high-risk status were
      associated with decreased likelihood of benign diagnostic category (OR .19 (95%
      CI .07-.51) and OR .40 (95% CI .18-.88), p values .001 and .022, respectively).
      CONCLUSIONS: 2% of patients undergoing abdominal US have sonographically
      indeterminate liver lesions, of which 7% are malignant. Older, high-risk patients
      with hypoechoic lesions should receive short-term follow-up as one-third will
      have malignant lesions. Younger, low-risk patients should receive conservative
      follow-up, regardless of US imaging features.

PMID- 29594467
TI  - Pancreatic neuroendocrine tumor: review of heterogeneous spectrum of CT
      appearance.
AB  - OBJECTIVE: Pancreatic neuroendocrine tumors (PanNETs) are uncommon pancreatic
      neoplasms and can be a diagnostic challenge with heterogeneous spectrum of CT
      appearance. We review CT findings of PanNETs and other mimics. CONCLUSION:
      PanNETs are typically hypervascular and have avid enhancement on arterial and
      venous phase images. However, dedicated pancreas protocol may be needed due to
      their sometimes atypical appearance including transient enhancement. Careful
      evaluation of CT findings will help differentiate PanNETs from their mimics, and
      can be used to establish the diagnosis of a PanNETs. Although an accurate
      diagnosis can be based on serological, urine, and CT scan findings, confirmation
      is made via pathological examination.

PMID- 29594468
TI  - Extensive spinal extradural ganglioneuroma of the lumbar spine: mimicking
      lymphoma.
AB  - BACKGROUND: Ganglioneuromas are rare, benign, well-differentiated tumors arising
      from neural crest cells that commonly occur in the posterior mediastinum,
      retroperitoneum, cervical spine, and adrenal gland. We report an unusual case of
      an extensive spinal extradural ganglioneuroma, circumferentially and
      longitudinally affecting the extradural space of the lumbar spine and
      continuously invading bilateral psoas muscles. CASE DESCRIPTION: A 32-year-old
      man presented with a 1-week history of abdominal pain and diarrhea. Radiographs
      revealed scalloping of the posterior surfaces of the L2 and L3 vertebral bodies
      and widening of L2-3 and L3-4 bilateral intervertebral foramina. Computed
      tomography scans and magnetic resonance imaging showed a well-defined lobulated
      extradural mass from L1 to L4 and a continuously forming mass in the psoas
      muscles through L2-3 bilateral neural foramina. The mass demonstrated
      homogeneously isointense signal on T1-weighted images, inhomogeneously
      hyperintense-to-isointense signal on T2-weighted images, and inhomogeneous
      enhancement on fat-suppressed contrast-enhanced T1-weighted images. Radiologic
      diagnosis included spinal epidural lymphoma. Percutaneous biopsy with sonographic
      guidance was performed, and the mass was diagnosed on pathological examination as
      a ganglioneuroma. CONCLUSIONS: This is the first known reported case in the
      literature of a spinal extradural ganglioneuroma with circumferentially and
      longitudinally extensive involvement of the extradural space and a large psoas
      mass.

PMID- 29594469
TI  - Letter to the Editor concerning "Relationship between preoperative serum rapid
      turnover proteins and early-stage surgical wound infection after spine surgery"
      by D. Kudo et al. (Eur Spine J; 2016: DOI 10.1007/s00586-016-4855-z).

PMID- 29594470
TI  - Testicular atrophy following inguinal hernia repair in children.
AB  - PURPOSE: We sought to determine the incidence and timing of testicular atrophy
      following inguinal hernia repair in children. METHODS: We used the TRICARE
      database, which tracks care delivered to active and retired members of the US
      Armed Forces and their dependents, including > 3 million children. We abstracted
      data on male children < 12 years who underwent inguinal hernia repair (2005
      2014). We excluded patients with history of testicular atrophy, malignancy or
      prior related operation. Our primary outcome was the incidence of the diagnosis
      of testicular atrophy. Among children with atrophy, we calculated median time to
      diagnosis, stratified by age/undescended testis. RESULTS: 8897 children met
      inclusion criteria. Median age at hernia repair was 2 years (IQR 1-5). Median
      follow-up was 3.57 years (IQR 1.69-6.19). Overall incidence of testicular atrophy
      was 5.1/10,000 person-years, with the highest incidence in those with an
      undescended testis (13.9/10,000 person-years). All cases occurred in children
      [Formula: see text] 5 years, with 72% in children < 2 years. Median time to
      atrophy was 2.4 years (IQR 0.64-3), with 30% occurring within 1 year and 75%
      within 3 years. CONCLUSION: Testicular atrophy is a rare complication following
      inguinal hernia repair, with children < 2 years and those with an undescended
      testis at highest risk. While 30% of cases were diagnosed within a year after
      repair, atrophy may be diagnosed substantially later. LEVEL OF EVIDENCE:
      Prognosis Study, Level II.

PMID- 29594471
TI  - Enzymatic biosensing by covalent conjugation of enzymes to 3D-networks of
      graphene nanosheets on arrays of vertically aligned gold nanorods: Application to
      voltammetric glucose sensing.
AB  - The authors demonstrate efficient direct electron transfer from the enzyme
      glucose oxidase to vertically aligned gold nanorods with a diameter of ~160 nm
      and a length of ~2 MUm that are covalently linkage to a 3-dimensional network of
      reduced graphene oxide nanosheets. The assembly can be prepared by a 2-step
      electrochemical procedure. This hybrid structure holds the enzyme in a favorable
      position while retaining its functionality that ultimately provides enhanced
      performance for enzymatic sensing of glucose without utilizing mediators. The
      nanorod assembly was applied to the voltammetric detection of glucose. Figures of
      merit include an electrochemical sensitivity of 12 MUA.mM-1.cm-2 (obtained from
      cathodic peak current at a voltage of -0.45 V vs. Ag/AgCl), a 3 MUM detection
      limit (at signal/noise = 3), and a wide linear range (0.01-7 mM). The hybrid
      nanostructure has a heterogeneous electron transfer rate constant (ks) of 2.9 s
      1. The high electrochemical activity is attributed to the synergistic effect of a
      large active surface and an enhanced electron transfer efficiency due to covalent
      amide linkage. Graphical Abstract Schematic of the procedure utilized for the
      fabrication of an electrochemical biosensor based on gold nanorods (AuNRs)
      modified with a reduced graphene oxide (rGO)/glucose oxidase (GOx) conjugate. The
      enzyme electrode was employed to the determination of glucose by differential
      pulse voltammetry.

PMID- 29594472
TI  - Matrix assisted laser desorption/ionization time-of-flight mass spectrometric
      determination of benzo[a]pyrene using a MIL-101(Fe) matrix.
AB  - A method is described for the matrix assisted laser desorption/ionization time-of
      flight (MALDI-TOF)-based determination of benzo[a]pyrene (BaP) by using the metal
      organic framework MIL-101(Fe) as a matrix. Following optimization of the
      experimental parameters, the method has a detection limit as low as 0.1 MUg.L-1,
      which makes it more sensitive than previous methods for BaP analysis, and its
      analysis time is only 1 min. Its applicability was evaluated by analyzing sesame
      oil, linseed oil, camellia seed oil, and olive oil spiked with BaP at three
      levels (10, 1, and 0.5 MUg.kg-1), and the recovery range was found to range from
      80.0 to 114.8% with relative standard deviations (RSDs) between 3.9 and 13.7%.
      Graphical abstract The metal-organic framework MIL-101(Fe) was applied as a new
      matrix to the quantitative detection of benzo[a]pyrene (BaP) by matrix assisted
      laser desorption/ionization time-of-flight (MALDI-TOF).

PMID- 29594473
TI  - Determination of norfloxacin or ciprofloxacin by carbon dots fluorescence
      enhancement using magnetic nanoparticles as adsorbent.
AB  - The authors describe a method for the determination of norfloxacin (NOR) or
      ciprofloxacin (CIP). It is making use of a combination of fluorescence
      enhancement and magnetic solid-phase extraction (MSPE). Sulfur-doped carbon dots
      (S-CDs) are used as a fluorescent probe. They were prepared by a one-pot method
      using poly(4-styrenesulfonic acid-co-maleic acid) (PSMA) as a source for carbon
      and sulfur. NOR or CIP act as sensitizers of fluorescence (with
      excitation/emission maxima at 324/412 nm), probably due to strong hydrogen bond
      interaction and charge transfer with the S-CDs. The S-CDs were characterized by
      using TEM, XRD, XPS, FT-IR, UV-Vis and fluorescence spectroscopies. Response is
      linear in the 0.02-1.25 MUM NOR concentration range, and the detection limit is
      4.6 nM. The respective data for CIP are 0.02-1.0 MUM and 6.7 nM. The average
      recoveries of NOR and CIP residues from spiked bovine raw milk are 96.2%~105.2%
      and 92.3%~102.5%. Graphical abstract Sulfur doped carbon dots (S-CDs) were
      synthesized by a hydrothermal method using poly(4-styrenesulfonic acid-co-maleic
      acid) (PSMA). Norfloxacin (NOR) or ciprofloxacin (CIP) was extracted by magnetic
      nanoparticles (MNPs), they were detected by carbon dots fluorescence enhancement.

PMID- 29594474
TI  - Fluorometric determination of lead(II) and mercury(II) based on their interaction
      with a complex formed between graphene oxide and a DNAzyme.
AB  - The authors have designed a DNAzyme where graphene oxide (GO) interacts with the
      ssDNA stem loop region. The DNAzyme strand and substrate strand are hybridized
      and bind to the surface of GO which act as a signal reporter, while GO act as a
      strong quencher. The presence of Pb(II) ion disturbs the GO-DNAzyme complex and
      causes internal cleavage of the DNAzyme complex. On addition of Thioflavin T
      (ThT) as a quadruplex inducer, fluorescence intensity (best measured at
      excitation/emission peaks of 425/490 nm) is strongly enhanced. Subsequent
      addition of Hg(II) to ThT/G-quadruplex complex decreases fluorescence because the
      G-quadruplex is unwinding to form a T-Hg(II)-T dsDNA system. Therefore, the
      change in fluorescence intensity of ThT is directly correlated to the
      concentration of Pb(II) and Hg(II). As a result, the assay is highly selective
      and sensitive. The limits of detection are 96 pM for Pb(II) and 356 pM for
      Hg(II). Moreover, the method was applied to the detection of the two ions in
      spiked real samples and gave satisfactory results. Graphical abstract A label
      free sensitive and selective "on-off" fluorescent assay for detection of Pb(II)
      and Hg(II) based on graphene oxide -DNAzyme complex with fluorogenic dye
      thioflavin T. The limits of detection are 96 pM (Pb2+) and 356 pM (Hg2+).

PMID- 29594475
TI  - Individual fatty acids in erythrocyte membranes are associated with several
      features of the metabolic syndrome in obese children.
AB  - PURPOSE: Obesity leads to the clustering of cardiovascular (CV) risk factors and
      the metabolic syndrome (MetS) also in children and is often accompanied by non
      alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can
      influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been
      proposed as beneficial in this setting. The aim of the study was to evaluate the
      associations of individual CV risk factors, characterizing the MetS, with
      erythrocyte membrane FA, markers of average intake, in a group of 70
      overweight/obese children. METHODS: We conducted an observational study.
      Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation
      coefficients (rS) were calculated to evaluate associations between FA and
      features of the MetS. RESULTS: Mean content of Omega-3 FA was low (Omega-3 Index
      = 4.7 +/- 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid
      (AA), were inversely associated with several features of the MetS: AA resulted
      inversely correlated with waist circumference (rS = - 0.352), triglycerides (rS =
      - 0.379), fasting insulin (rS = - 0.337) and 24-h SBP (rS = - 0.313). Total
      amount of saturated FA (SFA) and specifically palmitic acid, correlated
      positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and
      fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of
      steatosis based on GGT, triglycerides and anthropometric indexes, was positively
      correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = - 0.472).
      CONCLUSIONS: Our data suggest that omega-6 FA, and especially AA, could be
      protective toward CV risk factors featuring the MetS and also to indexes of
      hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.

PMID- 29594476
TI  - Geographic and socioeconomic diversity of food and nutrient intakes: a comparison
      of four European countries.
AB  - PURPOSE: Public health policies and actions increasingly acknowledge the climate
      burden of food consumption. The aim of this study is to describe dietary intakes
      across four European countries, as baseline for further research towards
      healthier and environmentally-friendlier diets for Europe. METHODS: Individual
      level dietary intake data in adults were obtained from nationally-representative
      surveys from Denmark and France using a 7-day diet record, Italy using a 3-day
      diet record, and Czech Republic using two replicates of a 24-h recall. Energy
      standardised food and nutrient intakes were calculated for each subject from the
      mean of two randomly selected days. RESULTS: There was clear geographical
      variability, with a between-country range for mean fruit intake from 118 to 199
      g/day, for vegetables from 95 to 239 g/day, for fish from 12 to 45 g/day, for
      dairy from 129 to 302 g/day, for sweet beverages from 48 to 224 ml/day, and for
      alcohol from 8 to 15 g/day, with higher intakes in Italy for fruit, vegetables
      and fish, and in Denmark for dairy, sweet beverages and alcohol. In all
      countries, intakes were low for legumes (< 20 g/day), and nuts and seeds (< 5
      g/day), but high for red and processed meat (> 80 g/day). Within countries, food
      intakes also varied by socio-economic factors such as age, gender, and
      educational level, but less pronounced by anthropometric factors such as
      overweight status. For nutrients, intakes were low for dietary fibre (15.8-19.4
      g/day) and vitamin D (2.4-3.0 ug/day) in all countries, for potassium (2288-2938
      mg/day) and magnesium (268-285 mg/day) except in Denmark, for vitamin E in
      Denmark (6.7 mg/day), and for folate in Czech Republic (212 ug/day). CONCLUSIONS:
      There is considerable variation in food and nutrient intakes across Europe, not
      only between, but also within countries. Individual-level dietary data provide
      insight into the heterogeneity of dietary habits beyond per capita food supply
      data, and this is crucial to balancing healthy and environmentally-friendly diets
      for European citizens.

PMID- 29594477
TI  - Quercetin inhibits intestinal non-haem iron absorption by regulating iron
      metabolism genes in the tissues.
AB  - PURPOSE: There is general agreement that some dietary polyphenols block non-haem
      iron uptake, but the mechanisms by which they achieve this action are poorly
      understood. Since the polyphenol quercetin is ingested daily in significant
      amounts, we have investigated the effect of quercetin on duodenal non-haem iron
      absorption in vivo, as well as its effect on factors known to be involved in
      systemic iron metabolism. METHODS: Rats were subject to gastric gavage and
      systemic quercetin administration. Treatments were followed with uptake studies
      using radiolabeled iron, serum iron and transferrin saturation measurements, LC
      MS/MS analysis of quercetin metabolites in serum, determination of tissue non
      haem iron content and analysis of gene expression of iron-related proteins.
      RESULTS: Both oral and intraperitoneal (IP) quercetin caused serum and tissue
      iron depletion by two means, first by increasing mucosal iron uptake and
      inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of
      duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly
      significant increased liver expression of hepcidin, a hormone known to inhibit
      intestinal iron uptake. CONCLUSIONS: Oral quercetin significantly inhibited iron
      absorption, while IP quercetin significantly affected iron-related genes. These
      results could lead to development of new effective ways of preventing and
      treating iron deficiency anaemia, the most widespread nutritional disorder in the
      world.

PMID- 29594478
TI  - Could Monopolar Mode be a Suitable Strategy of Energy Deposition for Performing
      No-Touch Radiofrequency Ablation of Liver Tumor <= 5 cm?

PMID- 29594479
TI  - Aptamer based fluorometric determination of ATP by exploiting the FRET between
      carbon dots and graphene oxide.
AB  - The authors describe a fluorometric aptamer based assay for adenosine
      triphosphate (ATP). It is based on the use of carbon dots (CDs) and graphene
      oxide (GO). The resultant CD-aptamer is adsorbed on the surface of GO via pi
      stacking and hydrophobic interaction, and the fluorescence of CD-aptamer is
      quenched via fluorescence resonance energy transfer (FRET) between CDs and GO. If
      ATP is present, it will bind to the aptamer and the CD-aptamer will be desorbed
      from GO. This will suppress FRET and the fluorescence of the CDs is restored.
      Under the optimal conditions and at typical excitation/emission wavelengths of
      358/455 nm, the assay has a 80 pM detection limit and a linear range that extends
      from 0.10 to 5.0 nM concentrations of ATP. The method was successfully applied to
      the determination of ATP in yogurt samples. This method can also be conceivably
      applied to the detection of other analytes for which appropriate aptamers are
      available. Graphical abstract Schematic of a novel fluorometric ATP assay based
      on the fluorescence resonance energy transfer (FRET) between aptamer modified
      carbon dots (CD-aptamer) and graphene oxide (GO). CD-aptamer was used as the
      energy donor and molecular recognition probe, and GO acted as energy acceptor.
      This assay exhibits high sensitivity and selectivity with a detection limit as
      low as 80 pM.

PMID- 29594480
TI  - Aptamer based electrochemiluminescent thrombin assay using carbon dots anchored
      onto silver-decorated polydopamine nanospheres.
AB  - An electrochemiluminescent (ECL) aptamer based assay is described for thrombin.
      It is based on the use of carbon dots (C-dots) placed on polydopamine nanospheres
      loaded with silver nanoparticles (PDANS@Ag) and with probe DNA (pDNA). The PDANS
      possess high specific surface and can load a large number of C-dots. The AgNPs,
      in turn, enhance the ECL emission of the C-dots. Platinum functionalized graphene
      (Gr-Pt) can connect capture DNA (cDNA). The ECL nanoprobe consisting of
      PDANS@Ag/C-dots was placed on a glassy carbon electrode modified with Gr
      Pt/cDNA/BSA via hybridization between cDNA and pDNA. On applying voltages from 
      1.8 V to 0 V, a strong ECL signal is generated. If thrombin is added, it will
      bind to cDNA. This leads to the release of pDNA from the electrode surface and a
      decrease in ECL intensity. Response to thrombin is linear in the 1.0 fmol.L-1 to
      5.0 nmol.L-1 concentration range, with a 0.35 fmol.L-1 detection limit. The assay
      is stable, repeatable and selective, which demonstrates its clinical
      applicability. Graphical abstract Carbon dots (C-dots) placed on polydopamine
      nanospheres loaded with silver nanoparticles (PDANS@Ag) for
      electrochemiluminescent (ECL) detection of thrombin.

PMID- 29594481
TI  - A graphene modified carbon ionic liquid electrode for voltammetric analysis of
      the sequence of the Staphylococcus aureus nuc gene.
AB  - The authors describe a voltammetric method for the detection of the nuc ssDNA
      sequence originating from Staphylococcus aureus by using a carbon ionic liquid
      electrode modified with electrodeposited three-dimensional graphene (3DGR). Probe
      ssDNA was electrostatically adsorbed on the modified electrode by a
      potentiostatic method. The porous structure and large surface area of 3DGR
      greatly increase the amount of immobilized probe ssDNA on the interface, which is
      beneficial for the reaction with target ssDNA. By using Methylene Blue (MB) as
      the electrochemical probe, the reduction peak current of MB (best measured at 
      0.30 V vs. SCE) can be used for detecting hybridization. The differential pulse
      voltammetric current of MB increases linearly in the 1.0 * 10-12 mol L-1 to 1.0 *
      10-6 mol L-1 nuc concentration range, and the detection limit is 3.3 * 10-13 mol
      L-1 (at 3sigma). The DNA sensor was successfully applied to the determination of
      the PCR product of the gene in pork. Graphical abstract Response of an
      electrochemical DNA biosensor based on the use of a carbon ionic liquid electrode
      modified with three-dimensional graphene. It enables sensitive voltammetric
      detection of the specific sequence of the Staphylococcus aureus nuc gene.

PMID- 29594482
TI  - Myoglobin immobilized on mesoporous carbon foam in a hydrogel (selep) dispersant
      for voltammetric sensing of hydrogen peroxide.
AB  - Mesoporous carbon foam (MCF) was prepared by via the Pechini method which is
      facile and template-free. The MCF was characterized by field emission scanning
      electron microscopy, transmission electron microscopy, X-ray diffraction and BET
      surface area analysis. Afterwards, the MCF was dispersed in the natural hydrogel
      salep to give a composite. Finally, myoglobin was immobilized on the composite
      and then placed on a glassy carbon electrode (GCE). The modified GCE gives a
      distinct quasi-reversible redox peak during electroreduction of hydrogen perxide
      (H2O2). The estimated electron transfer coefficient (alpha) and the heterogeneous
      electron transfer rate constant (ks) for redox process of Mb are 0.54 and 2.25 s
      1, respectively. The sensor, best operated at -0.2 V (vs. Ag/AgCl), responds to
      H2O2 in the 1.0 to 80 MUM H2O2 concentration range, with a 180 nM limit of
      detection (at S/N ratio of 3). The technique was applied to the determination of
      H2O2 in spiked fetal bovine serum samples. Graphical abstract Mesoporous carbon
      foam (MCF) synthesis, dispersion in Salep solution, preparing the Salep-MCF
      composite (S-MCF), immobilizing the Mb at S-MCF and preparing Mb/S-MCF composite,
      Casting the Mb/S-MCF on electrode surface to prepare Mb/S-MCF/GCE and
      electrochemical behavior of biosensor.

PMID- 29594483
TI  - Electrochemical determination of acetaminophen using a glassy carbon electrode
      modified with a hybrid material consisting of graphene aerogel and octadecylamine
      functionalized carbon quantum dots.
AB  - The study reports on the synthesis of a graphene aerogel@octadecylamine
      functionalized carbon quantum dots (GA@O-CQDs). The graphene oxide aqueous
      dispersion, O-CQDs aqueous dispersion and toluene were strongly mixed to make a
      toluene-in-water Pickering emulsion. The graphene oxide sheets in the aqueous
      phase are reduced by hydrazine hydrate, diffuse into the toluene droplets, and
      self-assemble into graphene oxide microgels. This is followed by freeze-drying
      and thermal annealing to obtain the GA@O-CQDs hybrid that has a three-dimensional
      structure of several microns. It was dispersed in ethanol and deposited on a
      glassy carbon electrode. The modified electrode was applied to differential pulse
      voltammetric determination of acetaminophen, best at a peak potential of 0.15 V
      (vs. Ag/AgCl). Figures of the merit include a wide linear response range (0.001
      10 MUM) and a 0.38 nM of the detection limit (S/N = 3). The assay has been
      applied to the determination of acetaminophen in tablets. Graphical abstract
      Schematic presentation of the synthesis of graphene aerogel@octadecylamine
      functionalized carbon quantum dots. The synthesis achieves to the intimate
      chemical and electrical contact between graphene and carbon quantum dots. An
      electrode modified with the hybrid exhibits ultra high sensitivity for detection
      of acetaminophen.

PMID- 29594484
TI  - Effects of Shengmai injection add-on therapy to chemotherapy in patients with non
      small cell lung cancer: a meta-analysis.
AB  - PURPOSE: Shengmai injection (SMI) has shown promising outcomes in the management
      of non-small cell lung cancer (NSCLC). This meta-analysis aimed to investigate
      the add-on effects of SMI to chemotherapy in NSCLC patients. METHODS: A
      comprehensive literature search was performed in the Cochrane Library, PubMed,
      Embase, CNKI, VIP, and Wanfang up to December 2017. Only randomized controlled
      trials (RCTs) evaluating SMI in combination with chemotherapy versus chemotherapy
      alone in NSCLC patients were eligible. The outcome measures were quality of life,
      chemotherapy-induced grade 3/4 myelosuppression or gastrointestinal reactions,
      and objective tumor response (equals complete response plus partial response).
      Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate
      dichotomous and continuous outcome, respectively. RESULTS: A total of 15 RCTs
      were included and analyzed. Meta-analysis showed that SMI combined with
      chemotherapy was associated with a significant improvement in Karnofsky
      Performance Status (RR 2.36; 95% CI 1.50-3.96) compared with the chemotherapy
      alone. Moreover, adjunctive treatment with SMI significantly reduced grade 3/4
      myelosuppression (RR 0.61; 95% CI 0.46-0.81) and gastrointestinal reactions (RR
      0.64; 95% CI 0.46-0.90). However, there was no significant difference in
      objective tumor response (RR 1.17; 95% CI 0.99-1.37) between two groups.
      CONCLUSIONS: SMI add-on therapy appeared to be more effective in improving
      quality of life and reducing chemotherapy-induced adverse effects. However, more
      well-designed RCTs are warranted to confirm the findings of this meta-analysis
      because of the suboptimal methodological quality of the included trials.

PMID- 29594485
TI  - Risk stratification of oxaliplatin induced peripheral neurotoxicity applying
      electrophysiological testing of dorsal sural nerve.
AB  - PURPOSE: We aimed to verify the predictiveness of dorsal sural nerve
      neurophysiological monitoring in obtaining risk stratification for oxaliplatin
      induced peripheral neurotoxicity (OXAPN). METHODS: We conducted a secondary
      analysis on a cohort of 110 colorectal cancer patients who were evaluated
      clinically and neurophysiologically before chemotherapy, at mid-treatment and at
      discontinuation. We applied the classification tree analysis method to predict
      the end-of-treatment OXAPN neurophysiological diagnosis, using data recorded at
      mid-treatment. We then ascertained the correlation between the obtained classes
      and neurological impairment at the end of treatment (Fisher's exact test).
      RESULTS: Dorsal sural nerve monitoring enabled us to stratify oxaliplatin-treated
      patients into risk classes with an implemented approach to neurophysiology
      application in this setting. Neurological outcome at discontinuation was
      predicted by neurophysiological monitoring performed during chemotherapy
      administration. CONCLUSIONS: We demonstrated the role that neurophysiology may
      play in clinical trials as an early surrogate marker that can predict OXAPN
      development at the end of treatment. Specifically, we propose abnormal dorsal
      sural sensory nerve testing as an early biomarker in identifying patients at high
      risk of eventually developing OXAPN.

PMID- 29594486
TI  - Perceptions of care and patient-reported outcomes in people living with
      neuroendocrine tumours.
AB  - BACKGROUND: Neuroendocrine tumours (NETs) are rare, and when metastatic NETs are
      incurable, the tumours are frequently slowly growing. Patients may be confronted
      with disease-specific problems and distinct issues when accessing health-care. We
      aimed to assess perceptions of care coordination, identify unmet needs, and
      examine if these varied by whether patients received specialist oncology care in
      a single hospital or shared between that and another hospital. We also quantified
      anxiety, depression, and NET-related physical symptoms. METHODS: We conducted a
      cross-sectional survey of 111 NET patients managed at Royal Brisbane and Women's
      Hospital. Validated surveys measured care coordination (CCCQ), unmet needs (SCNS
      SF34), anxiety and depression (HADS), and quality of life and symptoms (FACT).
      RESULTS: Participants were between 2 months and 27 years after diagnosis. The
      worst-ranked items on the CCCQ related to health professionals having a full case
      history, providing information about financial entitlements and asking about how
      well patients and their families were coping. People with shared care were
      significantly less satisfied with some aspects of care. One in three participants
      reported a moderate-to-high unmet need for help with fatigue and one in four with
      psychological concerns about their cancer spreading, uncertainty about their
      future, and about the worries of those close to them. Overall, 30% of
      participants had anxiety and 20% had depression and they had significantly lower
      physical and emotional well-being compared to the general population.
      CONCLUSIONS: NETs are experienced as a chronic illness. In addition to ongoing
      psychological and physical symptom management, improvements to case history
      documentation and discussions about coping and finance are recommended.

PMID- 29594487
TI  - 'Being with' or 'doing for'? How the role of an end-of-life volunteer befriender
      can impact patient wellbeing: interviews from a multiple qualitative case study
      (ELSA).
AB  - PURPOSE: To explore the perspectives of people anticipated to be in their last
      year of life, family carers, volunteers and staff on the impacts of receiving a
      volunteer-provided befriending service. Patient participants received up to 12
      weeks of a volunteer-provided befriending intervention. Typically, this involved
      one visit per week from a trained volunteer. Such services complement usual care
      and are hoped to enhance quality of life. METHODS: Multiple case study design (n
      = 8). Cases were end-of-life befriending services in home and community settings
      including UK-based hospices (n = 6), an acute hospital (n = 1) and a charity
      providing support to those with substance abuse issues (n = 1). Data collection
      incorporated qualitative thematic interviews, observation and documentary
      analysis. Framework analysis facilitated within and across case pattern matching.
      RESULTS: Eighty-four people participated across eight sites (cases), including
      patients (n = 23), carers (n = 3), volunteers (n = 24) and staff (n = 34).
      Interview data are reported here. Two main forms of input were described-'being
      there' and 'doing for'. 'Being there' encapsulated the importance of
      companionship and the relational dynamic between volunteer and patient. 'Doing
      for' described the process of meeting social needs such as being able to leave
      the house with the volunteer. These had impacts on wellbeing with people
      describing feeling less lonely, isolated, depressed and/or anxious. CONCLUSION:
      Impacts from volunteer befriending or neighbour services may be achieved through
      volunteers taking a more practical/goal-based orientation to their role and/or
      taking a more relational and emotional orientation. Training of volunteers must
      equip them to be aware of these differing elements of the role and sensitive to
      when they may create most impact. TRIAL REGISTRATION: ISRCTN12929812.

PMID- 29594488
TI  - On-line packed magnetic in-tube solid phase microextraction of acidic drugs such
      as naproxen and indomethacin by using Fe3O4@SiO2@layered double hydroxide
      nanoparticles with high anion exchange capacity.
AB  - The authors describe a 3-component nanoparticle system composed of a silica
      coated magnetite (Fe3O4) core and a layered double (Cu-Cr) hydroxide nanoplatelet
      shell. The sorbent has a high anion exchange capacity for extraction anionic
      species. A simple online system, referred to as "on-line packed magnetic-in-tube
      solid phase microextraction" was designed. The nanoparticles were placed in a
      stainless steel cartridge via dry packing. The cartridge was then applied to the
      preconcentration acidic drugs including naproxen and indomethacin from urine and
      plasma. Extraction and desorption times, pH values of the sample solution and
      flow rates of sample solution and eluent were optimized. Analytes were then
      quantified by HPLC with UV detection. Under optimal conditions, the limits of
      detection range from 70 to 800 ng L-1, with linear responses from 0.1-500 MUg L-1
      (water samples), 0.6-500 MUg L-1 (spiked urine), and 0.9-500 MUg L-1 (spiked
      plasma). The inter- and intra-assay precisions (RSDs, for n = 5) are in the range
      of 2.2-5.4%, 2.8-4.9%, and 2.0-5.2% at concentration levels of 5, 25 and 50 MUg L
      1, respectively. The method was applied to the analysis of the drugs in spiked
      human urine and plasma, and good results were achieved. Graphical abstract
      Fe3O4@SiO2@CuCr-LDH magnetic nanoparticles were synthesized and packed in to a
      stainless steel column. The column was applied to solid phase microextraction of
      acidic drugs from biological samples.

PMID- 29594489
TI  - Host genetic susceptibility to Clostridium difficile infections in patients
      undergoing autologous stem cell transplantation: a genome-wide association study.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is the most common hospital
      acquired infection. Unfortunately, genes that identify CDI-susceptible patients
      have not been well described. We performed a genome-wide association study (GWAS)
      to determine genetic variants associated with the development of CDI. METHODS: A
      cohort study of Caucasian patients undergoing autologous stem cell
      transplantation for multiple myeloma was performed. Patients were genotyped using
      Illumina(r) Whole Genome Genotyping Infinium chemistry. We then compared CDI
      positive to CDI-negative patients using logistic regression for baseline clinical
      factors and false discovery rate (FDR) for genetic factors [single nucleotide
      polymorphisms (SNPs)]. SNPs associated with CDI at FDR of p < 0.01 were then
      incorporated into a logistic regression model combining clinical and genetic
      factors. RESULTS: Of the 646 patients analyzed (59.7% male), 57 patients were
      tested CDI positive (cases) and were compared to 589 patients who were tested
      negative (controls). Hemoglobin, albumin, and hematocrit were lower for cases (p
      < 0.05). Eight SNPs on five genes (FLJ16171, GORASP2, RLBP1L1, ASPH, ATP7B) were
      associated with CDI at FDR p < 0.01. In the combined clinical and genetic model,
      low albumin and three genes RLBP1L1, ASPH, and ATP7B were associated with CDI.
      CONCLUSION: Low serum albumin and genes RLBP1L1 and ASPH located on chromosome 8
      and ATP7B on chromosome 13 were associated with CDI. Of particular interest is
      ATP7B given its copper modulatory role and the sporicidal properties of copper
      against Clostridium difficile.

PMID- 29594490
TI  - Bleeding frequency and characteristics among hematologic malignancy inpatient
      rehabilitation patients with severe thrombocytopenia.
AB  - OBJECTIVE: To identify the frequency and characteristics of bleeding
      complications during acute inpatient rehabilitation of hematologic malignancy
      patients with severe thrombocytopenia. DESIGN: Retrospective descriptive
      analysis. SETTING: Comprehensive cancer center acute inpatient rehabilitation
      unit. PARTICIPANTS: Consecutive hematologic malignancy patients with a platelet
      count of less than or equal to 20,000/microliter (MUL) on the day of acute
      inpatient rehabilitation admission from 1/1/2005 through 8/31/2016.
      INTERVENTIONS: Medical records were retrospectively analyzed for demographic,
      laboratory, and medical data. Patients were rehabilitated using the institutional
      exercise guidelines for thrombocytopenic patients. MAIN OUTCOME MEASURES:
      Bleeding events noted in the medical record. RESULTS: Out of 135 acute inpatient
      rehabilitation admissions, 133 unique patients were analyzed with a total of 851
      inpatient rehabilitation days. The mean platelet count was 14,000/MUL on the day
      of admission and 22,000/MUL over the course of the rehabilitation admission.
      There were 252 days of inpatient rehabilitation where patients had less than
      10,000/MUL platelets. A total of 97 bleeding events were documented in 77/135
      (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%)
      were considered to be of low, medium, and high severity, respectively. There were
      4/97 (4%) bleeding events that were highly likely attributable to physical
      activity but only 1/4 was considered high severity. Bleeding rates were .09, .08,
      .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/MUL mean platelet
      counts respectively (p = .003). Forty-four percent of patients were transferred
      back to the primary acute care service with infection being the most common
      reason for transfer. CONCLUSIONS: This study is the first to examine exercise
      related bleeding complications during acute inpatient rehabilitation in severely
      thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower
      platelet counts. However, using the exercise guidelines for severely
      thrombocytopenic patients, the risk of severe exercise-related bleeding events
      was low.

PMID- 29594491
TI  - Polypyrrole coated ZnO nanorods on platinum wire for solid-phase microextraction
      of amitraz and teflubenzuron pesticides prior to quantitation by GC-MS.
AB  - The authors describe a new sorbent for amitraz and teflubenzuron pesticides. It
      consists of a platinum wire coated with polypyrrole-coated ZnO nanorods. The
      nanocomposite was prepared by a two-step process. In the first step, oriented ZnO
      nanorods were hydrothermally grown in situ on a platinum wire. Subsequently,
      oxidative vapor phase polymerization of pyrrole was performed on FeCl3
      impregnated ZnO nanorods to give a porous polypyrrole film. The organic/inorganic
      nanocomposite synthesized through hydrothermal deposition and chemical vapor
      deposition polymerization yields material with attractive properties. The coated
      wire was applied to solid-phase microextraction of amitraz (in the form of 2,4
      dimethylaniline resulting from the hydrolysis of amitraz) and teflubenzuron. The
      effects of extraction temperature, extraction time, sample pH value and salt
      concentration were optimized. The analytes 2,4-dimethylaniline and teflubenzuron
      were then quantified by GC-MS. Under optimum conditions, the LODs range between
      0.1 and 0.15 ng.mL-1. Relative standard deviations at two concentration are <8.3%
      for intraday precision and <10.3% for inter-day precision. In all cases, the
      fiber to fiber reproducibility is <12.2%. For both analytes the linear dynamic
      ranges are 0.5-300 ng.mL-1. The procedure was successfully applied to the
      analysis of spiked agricultural water samples. Graphical abstract A novel
      inorganic/organic hybrid nanocomposite was synthesized through in situ
      hydrothermal deposition of ZnO nanorods and ten placing a thin layer of
      polypyrrole on them by chemical vapor deposition polymerization. This
      nanocomposite was applied to fabricate a solid-phase microextraction fiber for
      the extraction of amitraz and teflubenzuron pesticides residue from agricultural
      samples prior to their quantitation by GC-MS.

PMID- 29594492
TI  - Enzyme-free amplified detection of circulating microRNA by making use of DNA
      circuits, a DNAzyme, and a catalytic hairpin assembly.
AB  - A homogeneous and enzyme-free fluorometric assay is described for the
      determination of microRNA-182. It is based on the use of DNA circuits and
      DNAzyme. The DNA circuits warrant strong signal amplification by virtue of
      catalytic hairpin assembly, a system that consists of two hairpin substrates. A
      part of the DNAzyme sequence is programmed to sequester into one of the two
      hairpin substrates. In the presence of target microRNA-182, the two hairpin
      substrates undergo catalytic assembling. This results in the formation of a DNA
      duplex and the release of the DNAzyme from the hairpin structure. Upon cyclic
      amplification, one target catalyzes the formation of Mg (II)-dependent DNAzymes.
      These bind to, and hydrolyze, the fluorescently labeled substrates for signal
      amplification and transduction. Based on nucleic acid programmability, this
      engineered assay has a limit of detection as low as 6.8 f. and a dynamic range
      that covers the 10 f. to10 nM microRNA-182 concentration range. Detection can be
      performed within 60 min. The assay is simple, rapid, homogenous, cost-effective,
      and enzyme-free. These features make the method an attractive tool in routine
      microRNA diagnosis and, conceivably, in point of care uses. Graphical abstract
      Schematic of a homogeneous and enzyme-free fluorometric assay for the
      determination of microRNA-182. It is based on the use of DNA circuits and
      DNAzymes. The DNA circuits warrant strong signal amplification by virtue of
      catalytic hairpin assembly that uses two hairpin substrates. The method
      represents an attractive tool for routine microRNA diagnosis and, conceivably,
      point of care uses.

PMID- 29594493
TI  - Reliability of HR-pQCT Derived Cortical Bone Structural Parameters When Using
      Uncorrected Instead of Corrected Automatically Generated Endocortical Contours in
      a Cross-Sectional Study: The Maastricht Study.
AB  - Most HR-pQCT studies examining cortical bone use an automatically generated
      endocortical contour (AUTO), which is manually corrected if it visually deviates
      from the apparent endocortical margin (semi-automatic method, S-AUTO). This
      technique may be prone to operator-related variability and is time consuming. We
      examined whether the AUTO instead of the S-AUTO method can be used for cortical
      bone analysis. Fifty scans of the distal radius and tibia from participants of
      The Maastricht Study were evaluated with AUTO, and subsequently with S-AUTO by
      three independent operators. AUTO cortical bone parameters were compared to the
      average parameters obtained by the three operators (S-AUTOmean). All differences
      in mean cortical bone parameters between AUTO and S-AUTOmean were < 5%, except
      for lower AUTO cortical porosity of the radius (- 16%) and tibia (- 6%), and
      cortical pore volume (Ct.Po.V) of the radius (- 7%). The ICC of S-AUTOmean and
      AUTO was > 0.90 for all parameters, except for cortical pore diameter of the
      radius (0.79) and tibia (0.74) and Ct.Po.V of the tibia (0.89), without
      systematic errors on the Bland-Altman plots. The precision errors (RMS-CV%) of
      the radius parameters between S-AUTOmean and AUTO were comparable to those
      between the individual operators, whereas the tibia RMS-CV% between S-AUTOmean
      and AUTO were higher than those of the individual operators. Comparison of the
      three operators revealed clear inter-operator variability. This study suggests
      that the AUTO method can be used for cortical bone analysis in a cross-sectional
      study, but that the absolute values-particularly of the porosity-related
      parameters-will be lower.

PMID- 29594494
TI  - Amperometric detection of microRNA based on DNA-controlled current of a
      molybdophosphate redox probe and amplification via hybridization chain reaction.
AB  - An electrochemical sensor is described for the determination of microRNA-21 by
      combing the DNA generated current with target-triggered hybridization chain
      reaction (HCR). A thiol-modified hairpin capture probe was first immobilized on a
      gold electrode. In the presence of microRNA-21, hybridization leads to a
      conformational change of the capture probe. The conformational change triggers
      HCR to generate a long DNA strand on the surface of the electrode. The phosphate
      backbone of the long DNA strand then reacts with molybdate to form the redox
      redox probe molybdophosphate, and this generates an electrochemical current. The
      HCR triggered by microRNA increases the amount of phosphate groups due to the
      extension of the DNA length, and thus increases the response current. The
      electrode, best operated at a voltage of 0.20 V, was successfully applied to the
      analysis of microRNA-21 in (spiked) human serum samples. In our perception, it
      represents a promising tool for analyzing a variety of microRNA biomarkers.
      Graphical abstract Electrochemical sensor for detection of microRNA-21 by combing
      the DNA generated electrochemical current concept with target-triggered
      hybridization chain reaction (HCR) strategy is reported. DNA strands (S1 and S2)
      were assembled onto electrode through HCR reaction. MCH: 6-mercapto-1-hexanol.

PMID- 29594495
TI  - Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection:
      the role of isolated tumor cells/micrometastases and
      multifocality/multicentricity-a retrospective study of 1214 breast cancer
      patients.
AB  - PURPOSE: Sentinel lymph node biopsy (SLNB) alone has thus become an accepted
      surgical approach for patients with limited axillary metastatic disease. We
      investigated to what extent isolated tumor cells (ITC) or micrometastasis in
      SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph
      nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and
      multicentric tumors as both entities have been considered a contraindication for
      this technique. METHODS: 1214 women suffering from T1 and T2 invasive breast
      cancer, with clinically and sonographically insuspect axillary status and
      undergoing primary breast cancer surgery including SLNB and axillary staging in
      case of SLN (sentinel lymph node) metastases, were recruited into this
      multicentered study. RESULTS: ITC and micrometastases were found in 2.01 and
      21.4% of patients with SLN metastases (n = 299). Among patients with sentinel
      micrometastases, 4.7% showed further axillary micrometastases, while only two
      patients (3.1%) had two axillary macrometastases. Multifocal and multicentric
      tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN
      resected, respectively. Detection rates of SLNs did not differ between the
      cohorts suffering from unicentric and multifocal or multicentric disease.
      Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as
      well as the mean number of resected SLNs did not differ. CONCLUSIONS: No patient
      with sentinel node micrometastases showed more than two axillary macrometastases.
      Multifocal and multicentric disease is no contraindication for SLNB.

PMID- 29594496
TI  - pDHS-ELM: computational predictor for plant DNase I hypersensitive sites based on
      extreme learning machines.
AB  - DNase I hypersensitive sites (DHSs) are hallmarks of chromatin zones containing
      transcriptional regulatory elements, making them critical in understanding the
      regulatory mechanisms of gene expression. Although large amounts of DHSs in the
      plant genome have been identified by high-throughput techniques, current DHSs
      obtained from experimental methods cover only a fraction of plant species and
      cell processes. Furthermore, these experimental methods are both time-consuming
      and expensive. Hence, it is urgent to develop automated computational means to
      efficiently and accurately predict DHSs in the plant genome. Recently, several
      methods have been proposed to predict the DHSs. However, all these methods took a
      lot of time to build the model, making them inappropriate for data with massive
      volume. In the present work, a new ensemble extreme learning machine (ELM)-based
      model called pDHS-ELM was proposed to predict the DHSs in the plant genome by
      fusing two different modes of pseudo-nucleotide composition. Here, two kinds of
      features including reverse complement kmer and pseudo-nucleotide composition were
      used to represent the DHSs. The ELM model was used to build the base classifiers.
      Then, an ensemble framework was employed to combine the outputs of these base
      classifiers. When applied to DHSs in Arabidopsis thaliana and rice (Oryza sativa)
      genome, the proposed method could obtain accuracies up to 88.48 and 87.58%,
      respectively. Compared with the state-of-the-art techniques, pDHS-ELM achieved
      higher sensitivity, specificity, and Matthew's correlation coefficient with much
      less training and test time. By employing pDHS-ELM, we identified 42,370 and
      103,979 DHSs in A. thaliana and rice genome, respectively. The predicted DHSs
      were depleted of bulk nucleosomes and were tightly associated with transcription
      factors. Approximately 90% of the predicted DHSs were overlapped with
      transcription factors. Meanwhile, we demonstrated that the predicted DHSs were
      also associated with DNA methylation, nucleosome positioning/occupancy, and
      histone modification. This result suggests that pDHS-ELM can be considered as a
      new promising and powerful tool for transcriptional regulatory elements analysis.
      Our pDHS-ELM tool is available from the following website
      https://github.com/shanxinzhang/pDHS-ELM/ .

PMID- 29594497
TI  - A glassy carbon electrode modified with hollow cubic cuprous oxide for
      voltammetric sensing of L-cysteine.
AB  - This paper reports on an electrochemical sensing system for L-cysteine. It is
      based on the use of hollow cubic Cu2O particles that were prepared in two steps.
      First, the Cu2O/ polystyrene (PS) composites were prepared by a surface ion
      exchange strategy for in-situ reductive deposition on the surface of carboxy
      capped PS particles. Thereafter, the PS particles were removed from the Cu2O/PS
      composites by treatment with tetrahydrofuran (THF). The resulting hollow cubic
      Cu2O particles were placed in a Nafion matrix on a glassy carbon electrode (GCE)
      which exhibits high surface area, good site accessibility and excellent
      electrocatalytic activity for L-cysteine. The cyclic voltammetric response of the
      modified GCE to L-cysteine is about 2.8-fold stronger than when using a GCE
      modified with pure Cu2O. The detection limit for L-cysteine is lower by about 1
      order of magnitude, and the working voltage is rather low (-0.08 V vs. Ag/AgCl).
      An excellent electrochemical selectivity for L-cysteine over other amino acids
      was also achieved. The method was successfully applied to the determination of L
      cysteine in pharmaceutical samples. Graphical abstract An electrochemical sensing
      system for the detection of L-cysteine in amino acid injections has been
      established by using the hollow cubic Cu2O particles as recognition element.

PMID- 29594498
TI  - [Erratum to: pain and poverty].

PMID- 29594499
TI  - Herbivore removal reduces influence of arbuscular mycorrhizal fungi on plant
      growth and tolerance in an East African savanna.
AB  - The functional relationship between arbuscular mycorrhizal fungi (AMF) and their
      hosts is variable on small spatial scales. Here, we hypothesized that herbivore
      exclusion changes the AMF community and alters the ability of AMF to enhance
      plant tolerance to grazing. We grew the perennial bunchgrass, Themeda triandra
      Forssk in inoculum from soils collected in the Kenya Long-term Exclosure
      Experiment where treatments representing different levels of herbivory have been
      in place since 1995. We assessed AMF diversity in the field, using terminal
      restriction fragment length polymorphism and compared fungal diversity among
      treatments. We conducted clipping experiments in the greenhouse and field and
      assessed regrowth. Plants inoculated with AMF from areas accessed by wild
      herbivores and cattle had greater biomass than non-inoculated controls, while
      plants inoculated with AMF from where large herbivores were excluded did not
      benefit from AMF in terms of biomass production. However, only the inoculation
      with AMF from areas with wild herbivores and no cattle had a positive effect on
      regrowth, relative to clipped plants grown without AMF. Similarly, in the field,
      regrowth of plants after clipping in areas with only native herbivores was higher
      than other treatments. Functional differences in AMF were evident despite little
      difference in AMF species richness or community composition. Our findings suggest
      that differences in large herbivore communities over nearly two decades has
      resulted in localized, functional changes in AMF communities. Our results add to
      the accumulating evidence that mycorrhizae are locally adapted and that
      functional differences can evolve within small geographical areas.

PMID- 29594500
TI  - Fluorometric competitive immunoassay for chlorpyrifos using rhodamine-modified
      gold nanoparticles as a label.
AB  - A new kind of labelled antibody was synthesized by modifying gold nanoparticles
      (AuNPs) with the fluorophore rhodamine B isothiocyanate (RBITC) and a secondary
      antibody (IgG). The conjugate thus obtained was used in a competitive sandwich
      assay with a turn-on signal change. It was designed to detect the
      organophosphorus pesticide chlorpyrifos. The fluorescence of the RBITC-labeled
      gold immunoprobe with emission at 575 nm and excitation at 556 nm is almost
      completely quenched. If, however, cysteamine is added, the fluorophore is
      released from the labeled secondary antibody and fluorescence increases in
      accordance with the quantity of secondary antibody bound to the sandwich. This
      assay was applied to determine chlorpyrifos in dried tangerine peels. The
      detection results were also independently confirmed by LC-MS/MS. The method
      allows the concentrations of chlorpyrifos to be quantified down to 4.9 ng.mL-1,
      which is equivalent to 61 MUg.kg-1 in dried tangerine peels. In our perception,
      this approach has a wide potential to be applied in the determination of numerous
      analytes for which antibodies are available. Graphical abstract A new kind of
      labelled antibody was synthesized by modifying gold nanoparticles with
      fluorophore rhodamine B isothiocyanate (RBITC) and a secondary antibody (IgG).
      The conjugate was used in fluoroimmunoassay with a turn-on signal change. The
      method was designed to detect the organophosphorus pesticide chlorpyrifos.

PMID- 29594501
TI  - Mechanisms of Trabecular Formation and Specification During Cardiogenesis.
AB  - Trabecular morphogenesis is a key morphologic event during cardiogenesis and
      contributes to the formation of a competent ventricular wall. Lack of
      trabeculation results in embryonic lethality. The trabecular morphogenesis is a
      multistep process that includes, but is not limited to, trabecular initiation,
      proliferation/growth, specification, and compaction. Although a number of
      signaling molecules have been implicated in regulating trabeculation, the
      cellular processes underlying mammalian trabecular formation are not fully
      understood. Recent works show that the myocardium displays polarity, and oriented
      cell division (OCD) and directional migration of the cardiomyocytes in the
      monolayer myocardium are required for trabecular initiation and formation.
      Furthermore, perpendicular OCD is an extrinsic asymmetric cell division that
      contributes to trabecular specification, and is a mechanism that causes the
      trabecular cardiomyocytes to be distinct from the cardiomyocytes in compact zone.
      Once the coronary vasculature system starts to function in the embryonic heart,
      the trabeculae will coalesce with the compact zone to thicken the heart wall, and
      abnormal compaction will lead to left ventricular non-compaction (LVNC) and heart
      failure. There are many reviews about compaction and LVNC. In this review, we
      will focus on the roles of myocardial polarity and OCD in trabecular initiation,
      formation, and specification.

PMID- 29594503
TI  - Hyperphosphatemic tumoral calcinosis caused by FGF23 compound heterozygous
      mutations: what are the therapeutic options for a better control of phosphatemia?
AB  - BACKGROUND: Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare
      autosomal recessive disease caused by mutations in genes encoding FGF23 or its
      regulators, and leading to functional deficiency or resistance to fibroblast
      growth factor 23 (FGF23). Subsequent biochemical features include
      hyperphosphatemia due to increased renal phosphate reabsorption, and increased or
      inappropriately normal 1,25-dihydroxyvitamin D (1,25-D) levels. CASE
      DIAGNOSIS/TREATMENT: A 15-year-old girl was referred for a 1.2-kg-calcified mass
      of the thigh, with hyperphosphatemia (2.8 mmol/L); vascular impairment and soft
      tissue calcifications were already present. DNA sequencing identified compound
      heterozygous mutations in the FGF23 gene. Management with phosphate dietary
      restriction, phosphate binders (sevelamer, aluminum, nicotinamide), and
      acetazolamide moderately decreased serum phosphate levels; oral ketoconazole was
      secondary administered, leading to significantly decreased 1,25-D levels albeit
      only moderate additionally decreased phosphate levels. However, therapeutic
      compliance was questionable. Serum phosphate levels always remained far above the
      upper normal limit for age. The patient presented with two relapses of the thigh
      mass, requiring further surgery. CONCLUSIONS: We suggest that control of
      phosphate metabolism is crucial to prevent recurrences and vascular complications
      in HFTC; however, the medical management remains challenging.

PMID- 29594502
TI  - Fates Aligned: Origins and Mechanisms of Ventricular Conduction System and
      Ventricular Wall Development.
AB  - The cardiac conduction system is a network of distinct cell types necessary for
      the coordinated contraction of the cardiac chambers. The distal portion, known as
      the ventricular conduction system, allows for the rapid transmission of impulses
      from the atrio-ventricular node to the ventricular myocardium and plays a central
      role in cardiac function as well as disease when perturbed. Notably, its
      patterning during embryogenesis is intimately linked to that of ventricular wall
      formation, including trabeculation and compaction. Here, we review our current
      understanding of the underlying mechanisms responsible for the development and
      maturation of these interdependent processes.

PMID- 29594504
TI  - Management of high blood pressure in children: similarities and differences
      between US and European guidelines.
AB  - Over the last several decades, many seminal longitudinal cohort studies have
      clearly shown that the antecedents to adult disease have their origins in
      childhood. Hypertension (HTN), which has become increasingly prevalent in
      childhood, represents one of the most important risk factors for cardiovascular
      diseases (CVD) such as heart disease and stroke. With the risk of adult HTN much
      greater when HTN is manifest in childhood, the future burden of CVD worldwide is
      therefore concerning. In an effort to slow the current trajectory, professional
      societies have called for more rigorous, evidence-based guideline development to
      aid primary care providers and subspecialists in improving recognition,
      diagnosis, evaluation, and treatment of pediatric HTN. In 2016 the European
      Society of Hypertension and in 2017 the American Academy of Pediatrics published
      updated guidelines for prevention and management of high blood pressure (BP) in
      children. While there are many similarities between the two guidelines, important
      differences exist. These differences, along with the identified knowledge gaps in
      each, will hopefully spur clinical researchers to action. This review highlights
      some of these similarities and differences, focusing on several of the more
      important facets regarding prevalence, prevention, diagnosis, management, and
      treatment of childhood HTN.

PMID- 29594505
TI  - Urinary stone risk factors in the descendants of patients with kidney stone
      disease.
AB  - BACKGROUND: Evidence has indicated that immediate family members of
      nephrolithiasis patients had high opportunity to develop stones. However, they
      are usually not regarded to be at risk, since it is unclear if there are any
      lithogenic abnormalities found in non-stone-forming nephrolithiasis relatives.
      Our aim was to investigate urinary metabolic abnormalities in the children of
      nephrolithiasis patients, compared with the general population. METHODS: The 24-h
      urinary metabolic profile was studied for 28 calcium oxalate nephrolithiasis
      patients (NL) and 46 of their descendants (ND), as well as 40 non-stone-forming
      volunteers (V) and 34 of their descendants (VD). RESULTS: There was no difference
      between age, gender, and serum creatinine between NL vs. V (parental groups) and
      ND vs. VD (descendant groups). High urinary oxalate in nephrolithiasis and
      urinary calcium in their descendants was detected. In addition, an elevated
      urinary excretion rate of calcium, phosphate, protein, and albumin, along with
      low citrate excretion and high urinary supersaturation was observed in both the
      nephrolithiasis patients and their descendants. Approximate 17.8-24.4% of the
      nephrolithiasis descendants had a urinary supersaturation higher than the
      nephrolithiasis level, but none was found in VD group. The level of urinary
      supersaturation index was correlated with urinary protein and albumin excretion
      in nephrolithiasis family. CONCLUSION: It was demonstrated that nephrolithiasis
      offspring carried several urinary metabolic risks predisposing to stone formation
      which are similar to their parents, and about one in every five nephrolithiasis
      children had nephrolithiasis level urinary supersaturation.

PMID- 29594506
TI  - Obesity causes poorer clinical results and higher re-tear rates in rotator cuff
      repair.
AB  - BACKGROUND: The purpose of this retrospective study was to report on the
      functional outcome after both open and arthroscopic rotator cuff (RC) repair in
      normal weight, pre-obese and obese patients. It was hypothesized that obesity is
      a negative prognostic factor for clinical outcome and failure for the RC repair.
      METHODS: One hundred and forty-six patients who underwent either open or
      arthroscopic rotator cuff repair between 2006 and 2010 were included in this
      study. Seventy-five patients (56.7 +/- 10.1 years of age) after open RC repair
      and 71 patients (59.0 +/- 9.1 years of age) treated arthroscopically were
      available for evaluation. In both groups a double-row reconstruction was
      performed. Patients were divided in three groups according to their body-mass
      index. The mean follow-up was at 43 +/- 16 (minimum 24) months. At follow-up, the
      clinical outcome was assessed by the DASH and Constant score. An ultrasound of
      both shoulders was performed in all patients. RESULTS: The mean BMI was 28.3 +/-
      5.3 in the arthroscopic group and 27.7 +/- 4.3 in the open group. Overall, in
      both groups similar clinical results were noted [Constant-Murley score 78.3 +/-
      18.2 arthroscopic vs. 77.0 +/- 21.8 for open surgery; DASH 12.7 +/- 18.2
      arthroscopic vs. 15.6 +/- 21.6 for open surgery (p = 0.81)]. Both the failure
      rate and the clinical outcome were significantly worse for obese patients (BMI >
      30, p = 0.007). The failure rate was 15.8% for the normal-weight patients, 8.2%
      in the pre-obese group and in the obese group 28.6%. The RC repair failure
      occurred in 11 cases in both groups after arthroscopic or open treatment (15.0%).
      CONCLUSIONS: Both the arthroscopic and the open approach showed equivalent
      clinical results and failure rates. Obesity (BMI > 30) causes less favorable
      results in the Constant and DASH scores and showed higher re-tear rates.

PMID- 29594507
TI  - Graft extrusion after medial and lateral MAT differs according to surgical
      technique: a meta-analysis.
AB  - INTRODUCTION: It is unclear whether the incidence and amount of graft extrusion
      differ between knees undergoing medial and lateral meniscus allograft
      transplantation (MAT). This meta-analysis, therefore, compared the incidence and
      amount of transplanted meniscus allograft extrusion following medial and lateral
      MAT. MATERIALS AND METHODS: All studies comparing absolute or relative
      extrusions, or proportion of major extrusions (> 3 mm), on magnetic resonance
      imaging between medial and lateral MATs were included. RESULTS: Eight studies
      were included in the meta-analysis. Using the arthroscopic-assisted technique,
      medial MAT had significantly greater absolute (0.99 mm, p = 0.002) and relative
      (19.4%, p = 0.001) extrusions than lateral MAT. Using the complete arthroscopic
      technique, lateral MAT had 1.45 mm greater absolute extrusion than medial MAT (p
      < 0.001), but there was no difference in relative extrusion. Using the
      arthroscopic-assisted technique, the proportion of knees with major extrusion was
      greater for medial than lateral MAT (OR 5.32, p < 0.001), but, using the complete
      arthroscopic procedure, there was no difference in proportions of major
      extrusions between medial and lateral MAT (OR 0.28, p = 0.08). CONCLUSION: Graft
      extrusions after medial and lateral MAT differed according to surgical technique.
      Graft extrusion was greater after medial than lateral MAT using the arthroscopic
      assisted technique, but was greater after lateral than medial MAT using the
      complete arthroscopic procedure. LEVEL OF EVIDENCE: Meta-analysis (Level II).

PMID- 29594508
TI  - Wireless electrochemical preparation of gradient nanoclusters consisting of
      copper(II), stearic acid and montmorillonite on a copper wire for headspace in
      tube microextraction of chlorobenzenes.
AB  - This work introduces a new gradient fiber coating for microextraction of
      chlorobenzenes. Nanoclusters of organoclay-Cu(II) on a copper wire were
      fabricated by wireless electrofunctionalization. The resultant gradient coatings
      are more robust, and thermally and mechanically stable. Wireless
      electrofunctionalization was carried out in a bipolar cell under a constant
      deposition potential and using an ethanolic electrolyte solution containing
      stearic acid and montmorillonite. Stearic acid acts as an inexpensive and green
      coating while montmorillonite acts as a modifier to impart thermal stability. The
      gradient morphology of the nanoclusters was investigated by scanning electron
      microscopy, thermogravimetric analysis and energy dispersive X-ray spectroscopy.
      The coated wire was placed in a hollow needle and used for headspace in-tube
      microextraction (HS-ITME) of chlorobenzenes (CBs). Effects of various parameters
      affecting synthesis and extraction were optimized. Following extraction, the
      needles were directly inserted into the GC injector, and the CBs (chlorobenzene,
      1,4-dichlorobenzene, 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, 1,2,3,4
      tetrachlorobenzene) were quantified by GC-MS. The limits of detection under
      optimized conditions range from 0.5 to 10 ng.L-1. The intra- and inter-day
      relative standard deviations (RSDs) (for n = 10, 5 respectively) using a single
      fiber are 6-10 and 10-15%, respectively. The fiber-to-fiber RSDs (for n = 3) is
      between 17 and 24%. The method was successfully applied to the extraction of CBs
      from real water samples, and relative recoveries are between 91 and 110%.
      Graphical abstract A gradient coating of organoclay-Cu nanoclusters was
      fabricated on a copper wire by wireless electrofunctionalization. The oxidation
      of copper takes place at the anodic pole (red) while dissolved oxygen in ethanol
      solution is reduced at the cathodic pole (blue).

PMID- 29594509
TI  - Exertional heat illness incidence and on-site medical team preparedness in warm
      weather.
AB  - To investigate the influence of estimated wet bulb globe temperature (WBGT) and
      the International Institute of Race Medicine (IIRM) activity modification
      guidelines on the incidence of exertional heat stroke (EHS) and heat exhaustion
      (HEx) and the ability of an on-site medical team to treat those afflicted.
      Medical records of EHS and HEx patients over a 17-year period from the New
      Balance Falmouth Road Race were examined. Climatologic data from nearby weather
      stations were obtained to calculate WBGT with the Australian Bureau of
      Meteorology (WBGTA) and Liljegren (WBGTL) models. Incidence rate (IR) of EHS,
      HEx, and combined total of EHS and HEx (COM) were calculated, and linear
      regression analyses were performed to assess the relationship between IR and
      WBGTA or WBGTL. One-way ANOVA was performed to compare differences in EHS, HEx,
      and COM incidence to four alert levels in the IIRM guidelines. Incidence of EHS,
      HEx, and COM was 2.12, 0.98, and 3.10 cases per 1000 finishers. WBGTA explained
      48, 4, and 46% of the variance in EHS, HEx, and COM IR; WBGTL explained 63, 13,
      and 69% of the variance in EHS, HEx, and COM IR. Main effect of WBGTA and WBGTL
      on the alert levels were observed in EHS and COM IR (p < 0.05). The cumulative
      number of EHS patients treated did not exceed the number of cold water immersion
      tubs available to treat them. EHS IR increased as WBGT and IIRM alert level
      increased, indicating the need for appropriate risk mitigation strategies and on
      site medical treatment.

PMID- 29594510
TI  - Carbon nanotube-modified monolithic polymethacrylate pipette tips for
      (micro)solid-phase extraction of antidepressants from urine samples.
AB  - This work evaluates the potential of methacrylate monoliths with multi-walled
      carbon nanotubes incorporated into the polymeric network for the extraction of
      antidepressants from human urine. The method is based on a micropipette solid
      phase extraction tip containing a hybrid monolithic material covalently attached
      to the polypropylene housing. A polymer layer made from poly(ethylene
      dimethacrylate) was bound to the inner surface of a polypropylene tip via UV
      grafting. The preparation of the monolith and the microextraction steps were
      optimized in terms of adsorption capacity. Limits of detection ranged from 9 to
      15 MUg.L-1. The average precision of the method varied between 3 and 5% (intra
      tips), and from 4 to 14% (inter-tips). The accuracy of the method was evaluated
      through a recovery study by using spiked samples. Graphical abstract Hybrid
      polymer monoliths containing multi-walled carbon nanotubes (MWCNTs) were prepared
      in pipette tips by photo-polymerization approach. The extraction devices were
      used for the extraction of antidepressants in urine samples.

PMID- 29594511
TI  - Improving the sensitivity of immunoassays by reducing non-specific binding of
      poly(acrylic acid) coated upconverting nanoparticles by adding free poly(acrylic
      acid).
AB  - Upconverting nanoparticles (UCNPs) are attractive reporters in immunoassays
      because of their outstanding detectability. However, non-specific binding of
      antibody-UCNP conjugates on protein coated solid support results in background,
      which limits the immunoassay sensitivity. Thus, the full potential of UCNPs as
      reporters cannot be fully exploited. The authors report here a method to improve
      the sensitivity of UCNP-based immunoassays by reducing the non-specific binding
      of antibody-UNCP conjugates on the protein coated solid support. In the assays
      studied here, poly(acrylic acid) (PAA) coated NaYF4:Yb3+,Er3+ type UCNPs were
      conjugated to two different antibodies against cardiac troponin I (cTnI) and
      thyroid stimulating hormone (TSH). The two-step heterogeneous sandwich
      immunoassays were performed in microtitration wells, and the green luminescence
      of antibody-UCNP conjugates was measured at 540 nm upon 980 nm excitation. Non
      specific binding of antibody-UCNP conjugates was reduced by mixing free PAA with
      PAA coated UCNPs before adding the UCNPs to the wells. The free PAA in the buffer
      reduced the background in both cTnI and TSH immunoassays (compared to the control
      assay without free PAA). The limits of detection decreased from 2.1 ng.L-1 to
      0.48 ng.L-1 in case of cTnI and from 0.070 mIU.L-1 to 0.020 mIU.L-1 in case of
      TSH if PAA is added to the buffer. Presumably, the effect of free PAA is due to
      blocking of the surface areas where PAA coated UCNP would bind proteins non
      specifically. The method introduced here is likely to be applicable to other
      kinds of PAA-coated nanoparticles, and similar approaches conceivably work also
      with other nanoparticle coatings. Graphical abstract The presence of free
      poly(acrylic acid) (PAA) in a buffer solution prevents aggregation and non
      specific protein binding of PAA-coated upconverting nanoparticles (UCNPs) in
      heterogeneous sandwich immunoassays. The decrease in non-specific binding enables
      distinctly more sensitive assays to be performed.

PMID- 29594512
TI  - Correction to: Loop-mediated isothermal amplification for visual detection of
      Vibrio parahaemolyticus using gold nanoparticles.
AB  - The published version of this article, unfortunately, contained error.
      Modifications have been made to the Abstract, Introduction, Results and
      discussion, and Acknowledgements section. The original article has been
      corrected.

PMID- 29594513
TI  - Preparation of a nanocomposite material consisting of cuprous oxide, polyaniline
      and reduced graphene oxide, and its application to the electrochemical
      determination of hydrogen peroxide.
AB  - A method is described for the preparation of a nanocomposite material consisting
      of cuprous oxide/polyaniline/reduced graphene oxide (Cu2O/PANI/rGO). Aniline was
      employed as both the precursor for PANI and the reducing agent for Cu2+ and
      graphene oxide. A glassy carbon electrode was modified with the nanocomposite
      material. Chronoamperometric studies with the modified electrode showed it to
      enable an efficient electroreduction of hydrogen peroxide at -0.2 V vs. saturated
      calomel electrode. All measurements were performed in the absence of oxygen.
      Figures of merit include a wide linear response range (0.8 MUM to 12.78 mM) and a
      low limit of detection of 0.5 MUM (S/N = 3). Graphical abstract Cuprous
      oxide/polyaniline/reduced graphene oxide nanocomposites were synthesized through
      one-step process for fabricating an nonenzymatic electrochemical sensor for
      hydrogen peroxide.

PMID- 29594514
TI  - ...why remifentanil?

PMID- 29594516
TI  - Amperometric determination of nitrite using natural fibers as template for
      titanium dioxide nanotubes with immobilized hemin as electron transfer mediator.
AB  - A sensing device was constructed for the amperometric determination of nitrite.
      It is based on the use of titanium dioxide (TiO2) nanotubes template with natural
      fibers and carrying hemin acting as the electron mediator. A glassy carbon
      electrode (GCE) was modified with the hemin/TNT nanocomposite. The
      electrochemical response to nitrite was characterized by impedance spectroscopy
      and cyclic voltammetry. An amperometric study, performed at a working potential
      of + 0.75 V (vs. Ag/AgCl), showed the sensor to enable determination of nitrite
      with a linear response in the 0.6 to 130 MUM concentration range and with a 59 nM
      limit of detection. Corresponding studies by differential study voltammetry (Ep =
      0.75 V) exhibited a linear range from 0.6 * 10-6 to 7.3 * 10-5 M with a limit of
      detection of 84 nM. The sensing device was applied to the determination of
      nitrite in spiked tap and lake water samples. Graphical abstract Natural fibers
      templated synthesis of TNT immobilized hemin as electron transfer mediator for
      quantitative detection of nitrite with detection limit of 59 nM and good
      electrochemical sensitivity and the method can be used for quantitative
      determination of nitrite in water samples.

PMID- 29594515
TI  - The response to DNA damage in heterochromatin domains.
AB  - Eukaryotic genomes are organized into chromatin, divided into structurally and
      functionally distinct euchromatin and heterochromatin compartments. The high
      level of compaction and the abundance of repeated sequences in heterochromatin
      pose multiple challenges for the maintenance of genome stability. Cells have
      evolved sophisticated and highly controlled mechanisms to overcome these
      constraints. Here, we summarize recent findings on how the heterochromatic state
      influences DNA damage formation, signaling, and repair. By focusing on distinct
      heterochromatin domains in different eukaryotic species, we highlight the
      heterochromatin contribution to the compartmentalization of DNA damage repair in
      the cell nucleus and to the repair pathway choice. We also describe the diverse
      chromatin alterations associated with the DNA damage response in heterochromatin
      domains and present our current understanding of their regulatory mechanisms.
      Finally, we discuss the biological significance and the evolutionary conservation
      of these processes.

PMID- 29594517
TI  - Colorimetric and visual determination of Au(III) ions using PEGylated gold
      nanoparticles.
AB  - A highly selective method is described for the colorimetric determination of
      Au(III) ions in acidic solution using gold nanoparticles (AuNPs) functionalized
      with thiolated methoxy poly(ethylene glycol) (mPEG). The presence of Au(III)
      induces the aggregation of the PEG-AuNPs, and this is accompanied by a color
      change from wine red to blue, and a decrease in absorbance at 525 nm. This can be
      monitored spectrophotometrically and visually. Absorbance at 525 nm linearly
      drops in the 0.50 to 1.75 mg.L-1 Au(III) concentration range, with a 0.25 mg.L-1
      detection limit. The method is surprisingly selective over other metal ions. It
      was successfully applied to the analysis of ore samples. Graphical Abstract ?.

PMID- 29594518
TI  - Quick colorimetric determination of choline in milk and serum based on the use of
      MoS2 nanosheets as a highly active enzyme mimetic.
AB  - The authors have synthesized molybdenum disulfide nanosheets (MoS2 nanosheets) by
      using a bottom-up hydrothermal method. The nanosheets display strong catalytic
      (enzyme mimetic) activity in catalyzing the oxidation of peroxidase substrate of
      3,3',5,5'-tetramethylbenzidine (TMB) in presence of H2O2 to produce a blue
      product. The peroxidase mimicking properties of MoS2 nanosheets depend on
      temperature, H2O2 concentration and pH value. A choline assay was worked out
      where choline was oxidized by choline oxidase in presence of oxygen to produce
      H2O2 which is colorimetrically detected, best at 652 nm. The method works in the
      1 to 180 MUM choline concentration range with a 0.4 MUM detection limit. Color
      changes may also be detected visually. The assay is simple, highly sensitive,
      selective and rapid. It was applied in the determination of choline in (spiked)
      milk and serum. Graphical abstract Basic principle of intrinsic peroxidase-like
      activity of MoS2 nanosheets, applied to design a rapid and selective colorimetric
      assay for choline detection based on the tetramethylbenzidine (TMB) color
      reaction.

PMID- 29594519
TI  - Electrochemical prostate specific antigen aptasensor based on hemin
      functionalized graphene-conjugated palladium nanocomposites.
AB  - An electrochemical aptasensor is described for the detection of prostate specific
      antigen (PSA). The aptasensor is based on the use of hemin-functionalized
      graphene-conjugated palladium nanoparticles (H-Gr/PdNPs) deposited on a glassy
      carbon electrode. The nanocomposites integrate the high electrical conductivity
      of graphene with the easily functionalized surface chemistry of PdNPs and their
      excellent catalytic property. The hemin placed on graphene acts as both a
      protective agent and an in-situ redox probe. The PdNPs provide numerous binding
      sites for the immobilization of DNA-biotin via coordinative binding between Pd
      and amino groups. A sensitive and specific PSA assay was attained by immobilizing
      the PSA aptamer via biotin-streptavidin interaction. The resulting aptasensor has
      a linear response that covers the PSA concentration range from 0.025 to 205 ng.mL
      1, with a 8 pg.mL-1 lower detection limit (at -0.362 V, scan rate: 0.1 mV.s-1,
      S/N = 3). The method was applied to the quantitation of PSA in spiked serum
      samples, giving recoveries ranging from 95.0 to 100.3%. Graphical abstract A
      signal amplified and approving electrochemical aptasensor was constructed for the
      determination of prostate specific antigen (PSA) based on the use of hemin
      functionalized graphene conjugated to palladium nanoparticles (H-Gr/PdNPs). The
      sensor has a wide linear range, a relatively low detection limit, satisfying
      stability and high specificity.

PMID- 29594520
TI  - Highly sensitive and selective determination of copper(II) based on a dual
      catalytic effect and by using silicon nanoparticles as a fluorescent probe.
AB  - The authors describe a silicon nanoparticle-based fluorometric method for
      sensitive and selective detection of Cu2+. It is based on the catalytic action of
      Cu2+ on the oxidation of cysteine (Cys) by oxygen to form cystine and the by
      product H2O2. The generated H2O2 is catalytically decomposed by Cu2+ to generate
      hydroxyl radicals which oxidize and destroy the surface of SiNPs. As a result,
      the blue fluorescence of the SiNPs is quenched. The method has excellent
      selectivity due to the dual catalytic effects of Cu2+, which is much better than
      most previously reported nanomaterial-based assays for Cu2+. Under the optimal
      conditions, the method has low detection limit (29 nM) and a linear response in a
      concentration range from 0.05 MUM to 15 MUM. The method has been successfully
      applied to the determination of Cu2+ in spiked real water samples, and the
      results agreed well with those obtained by the Chinese National Standard method
      (GB/T 7475-1987; AAS). Graphical abstract Schematic presentation of a
      fluorometric method for the determination of Cu2+ based on the dual catalytic
      effects of Cu2+, and the oxidative effect of hydroxy radicals on the surface of
      silicon nanoparticles (SiNPs). The method has a 29 nM detection limit and good
      selectivity.

PMID- 29594521
TI  - Cortical neural arousal is differentially affected by type of physical exercise
      performed.
AB  - Critical flicker frequency (CFF) threshold is a visual discrimination task
      designed to assess cortical neural arousal, where higher values are associated
      with increased information processing and improved cognitive function. Previous
      studies using CFF assessments before and after exercise have only used one type
      of exercise (e.g., short, fatiguing, steady state, time to exhaustion, etc.).
      Therefore, the purpose of this study was to determine the effect of exercise type
      and intensity on neural arousal. 22 recreational runners (10 men, 12 women; age
      25 +/- 6 years) volunteered to participate in the study. They completed a VO2max
      test (short, fatiguing trial), and three 30-min treadmill runs (longer, steady
      state trials) at rating of perceived exertion (RPE) levels of 13, 15, and 17.
      Before and after each exercise test, subjects were asked to complete the CFF
      test; Mtot and Mdi were calculated, which are the average and difference of the
      ascending/descending frequency trials, respectively. There were no main effects
      found for either intensity (p = 0.641) or time (p = 0.283); there was, however, a
      significant interaction found (intensity*time; p = 0.001). In the VO2max test and
      in the longer, steady-state runs at RPE13 and 15, there was no change in Mtot.
      There was a significant increase in Mtot after the run at RPE17 (p = 0.019). For
      Mdi, the VO2max test elicited a significant decrease (p = 0.005), but there was
      no change after the steady-state runs. The results suggest that short, fatiguing
      and longer, steady-state exercise affect cortical neural arousal differently.
      Increases in arousal, and perhaps the related domain of information processing,
      are more likely to come from steady-state exercise at a vigorous intensity.

PMID- 29594522
TI  - Turn-on fluorometric and colorimetric probe for hydrogen peroxide based on the in
      situ formation of silver ions from a composite made from N-doped carbon quantum
      dots and silver nanoparticles.
AB  - The authors describe a fluorometric and colorimetric nanoprobe for H2O2. The
      detection scheme is based on the in-situ formation of silver(I) ions from a
      composite consisting of nitrogen-doped carbon quantum dots (N-CQDs) and silver
      nanoparticles (AgNPs). A drastic change occurs both in fluorescence and color of
      the solution of the N-CQD/AgNPs composite. The fluorescence of composite (with
      excitation/emission peaking at 320/384 nm) is enhanced on increasing the
      concentration of H2O2 due to the oxidation of silver metal in the N-CQD/AgNPs to
      form Ag(I) ions. The latter undergo strong coordination with the nitrogen atoms
      of the N-CQDs. In-situ formation of Ag(I) ions further results in a change in
      color of the solution from pale yellow (with a peak at 408 nm) to colorless.
      Under optimized conditions, the probe gives a fluorometric and colorimetric
      response in the 10 to 50 MUM H2O2 concentration range with a 4.7 MUM limit of
      detection. The probe is highly selective over several potentially interfering
      ions and agents. It was successfully applied to the determination of H2O2 in
      spiked samples without prior treatment. Graphical abstract Graphical presentation
      for specific detection of H2O2 based on the in-situ formation of Ag(I) ions from
      a composite consisting of silver nanoparticles and nitrogen-doped carbon quantum
      dots.

PMID- 29594523
TI  - Red emitting and highly stable carbon dots with dual response to pH values and
      ferric ions.
AB  - The authors describe strongly red-emitting carbon dots (CDs) which were obtained
      via microwave synthesis using phenylenediamine as the carbon source. The
      structural and optical properties of the resultant CDs are studied in some
      detail. The CDs possess (a) longwave emission (peaking at 620 nm under 470 nm
      excitation), (b) a quantum yield of ~15%, (c) a size of typically 3.8 nm; and (d)
      good photostability. The CDs have a pH-dependet response that covers the pH 5 to
      10 range, and their fluorescence is quenched by ferric ions. The CDs can detect
      ferric ions in aqueous samples in the 0 to 30 MUM concentration range with a
      lower detection limit of 15 nM. The CDs were also used to image pH values and
      ferric ions in E. coli bacteria. Graphical abstract The red-emitting carbon dots
      with high stability are synthesized which show dual response to pH-values and
      ferric ions in aqueous solution and biological media simultaneously.

PMID- 29594524
TI  - Silicon nanoparticles coated with an epitope-imprinted polymer for fluorometric
      determination of cytochrome c.
AB  - The authors describe a composite consisting of silicon nanoparticles that were
      first coated with SiO2 and then with a molecularly imprinted polymer
      (SiNP@SiO2@MIP). The MIP was generated by dual epitope imprinting such that it
      can recognize cytochrome c (Cyt c). The MIP on the NPs was prepared from the
      functional monomer zinc(II) acrylate (ZnA), the crosslinker ethylene glycol
      dimethacrylate and the initiator 2,2'-azoisobutyronitrile. Dual epitope templates
      for Cyt c included (a) a C-terminal nonapeptide (AYLKKATNE), and (b) an N
      terminal nonapeptide (GDVEKGKKI). The chelation between Zn(II) of ZnA and the
      amino groups or hydroxy groups of the template nonapeptides warrants good
      recognition and capture of Cyt c. The fluorescence originating from SiNPs has
      excitation/emission peaks at 360/480 nm and is quenched by Cyt c in the 0.50-40.0
      MUM concentration range. The correlation coefficient for the calibration plot of
      the imprinted NPs is 0.9937. The detection limit is 0.32 +/- 0.01 MUM, the
      precisions of six replicate detections at levels of 0.5, 20 and 40 MUM Cyt c are
      3.2, 2.7 and 2.8%, respectively, and the imprinting factor is 2.43. Compared to
      single epitope template imprinting, dual epitope imprinting results in improved
      selectivity. The imprinted nanoparticles can discriminate Cyt c even if one amino
      acid is mismatched. The method was applied to the determination of Cyt c in
      spiked diluted human serum and gave recoveries between 94.0 and 107.5%. Graphical
      Abstract A fluorescent material of the architecture silicon
      nanoparticle@SiO2@molecularly imprinted polymer (SiNP@SiO2@MIP) was fabricated by
      dual epitope imprinting and a metal-chelating method. The chelation between
      Zn(II) of the functional monomer zinc(II) acrylate and the amino groups or
      hydroxy groups of template warrants that the material recognizes and captures
      cytochrome c well, and this results in fluorescence quenching.

PMID- 29594525
TI  - Bioimaging of metallothioneins in ocular tissue sections by laser ablation-ICP-MS
      using bioconjugated gold nanoclusters as specific tags.
AB  - An immunohistochemical method is described to visualize the distribution of
      metallothioneins 1/2 (MT 1/2) and metallothionein 3 (MT 3) in human ocular
      tissue. It is making use of (a) antibodies conjugated to gold nanoclusters
      (AuNCs) acting as labels, and (b) laser ablation (LA) coupled to inductively
      coupled plasma - mass spectrometry (ICP-MS). Water-soluble fluorescent AuNCs
      (with an average size of 2.7 nm) were synthesized and then conjugated to antibody
      by carbodiimide coupling. The surface of the modified AuNCs was then blocked with
      hydroxylamine to avoid nonspecific interactions with biological tissue.
      Immunoassays for MT 1/2 and MT 3 in ocular tissue sections (5 MUm thick) from two
      post mortem human donors were performed. Imaging studies were then performed by
      fluorescence using confocal microscopy, and LA-ICP-MS was performed in the retina
      to measure the signal for gold. Signal amplification by the >500 gold atoms in
      each nanocluster allowed the antigens (MT 1/2 and MT 3) to be imaged by LA-ICP-MS
      using a laser spot size as small as 4 MUm. The image patterns found in retina are
      in good agreement with those obtained by conventional fluorescence
      immunohistochemistry which was used as an established reference method. Graphical
      abstract Gold nanoclusters (AuNCs) conjugated to a primary specific antibody
      serve as a label for amplified bioimaging of metallothioneins (MTs) by laser
      ablation coupled to inductively coupled plasma - mass spectrometry (ICP-MS) in
      human ocular tissue sections.

PMID- 29594526
TI  - Nanodiamonds conjugated to gold nanoparticles for colorimetric detection of
      clenbuterol and chromium(III) in urine.
AB  - Nanodiamonds were modified such that they carry thiol groups (ND-thiol). Gold
      nanoparticles were reacted with ND-thiol to obtain a highly stable conjugate of
      the type ND@AuNPs. Both ND-thiol and the ND@AuNPs were characterized by SEM, TEM,
      AFM, DLS, zeta potential, XPS, XRD, UV-Vis, Raman, FTIR and cytotoxicity studies.
      Their biocompatibility was confirmed via an MTT assay with HeLa cells. At a pH
      value of 6, the ND@AuNPs represent a colorimetric probe that can be used to
      selectively detect the illegally used beta-adrenergic drug clenbuterol (CLB) and
      the pollutant chromium(III). Detection can be performed visually by monitoring
      the color change from wine red to purple blue, or by colorimetric measurement of
      the so-called SPR peaks at 651 and 710 nm. The color changes are due to
      aggregation, and this is confirmed by TEM and DLS data. The involvement of
      surface functional groups that assist in analyte recognition was verified by
      FTIR. The detection limits are 0.49 nM for CLB, and 0.37 nM for Cr(III). The
      ND@AuNPs were successfully applied to the determination of Cr(III) and CLB in
      spiked human urine samples. Notably, the low interference by other ions in the
      detection of Cr(III) in tap and lake water is confirmed by ICP-MS analyses.
      Graphical abstract Nanodiamonds carrying thiol groups (ND-Thiol) were conjugated
      to gold nanoparticles, and the resulting ND@AuNPs are shown to be viable probes
      for the colorimetric detection of sub-nanomolar levels of clenbuterol (CLB) and
      Cr(III) ions, with demonstrated applicability to real water and urine samples.

PMID- 29594527
TI  - Matched cohort study of topical tranexamic acid in cementless primary total hip
      replacement.
AB  - PURPOSE: Tranexamic acid has been shown to be effective in reducing blood loss
      after total hip replacement. The purpose of this study was to prospectively
      assess the effectiveness of topical TXA use to reduce blood loss after primary
      total hip replacement and to compare these outcomes with those of a matched
      control group from a similar cohort that did not have received tranexamic acid.
      METHODS: This is a prospective matched control study to assess the effect of a 2
      g topical tranexamic acid in 50 mL physiological saline solution in total hip
      replacement. Primary outcomes were hemoglobin and hematocrit drop, and total
      blood loss. Secondary outcomes were transfusion rates, length of hospital stay,
      deep vein thrombosis, and pulmonary embolism events. RESULTS: We could match 100
      patients to a control group. There were no statistical significantly differences
      between the two groups. The hemoglobin and hematocrit postoperative values were
      significantly higher in topical tranexamic acid group than in control group (P <
      0.001). The mean total blood loss was 769 in topical tranexamic acid group and
      1163 in control group with significant differences (P = 0.001), which meant 34%
      reduction in total blood loss. Length of stay was lower in topical tranexamic
      acid group. The risk of deep vein thrombosis and pulmonary events did not
      increase. CONCLUSIONS: A single dose of 2 g tranexamic acid in 50 mL
      physiological saline solution topical administration was effective and safe in
      reducing bleeding in patients undergoing unilateral primary non-cemented total
      hip replacement compared to a matched control group.

PMID- 29594528
TI  - Comparing the efficacy of intravenous or intra-articular tranexamic acid in
      reducing blood loss in simultaneous bilateral knee replacement surgery without
      the use of tourniquet.
AB  - PURPOSE: To compare the effect of intravenous or intra-articular route of
      administration of tranexamic acid in reducing the blood loss in simultaneous
      bilateral total knee replacement surgeries performed without the use of
      tourniquets. METHODS: Prospective cohort study of 30 consecutive patients grouped
      into two groups; Group 1: intravenous group and group 2: intra-articular group.
      Two outcome measures were studied; mean drop in post-operative haemoglobin and
      need for blood transfusion in both groups. RESULTS: No significant difference in
      mean drop of haemoglobin and need for blood transfusion in both groups.
      CONCLUSION: Route of administration of tranexamic acid does not influence on the
      mean drop of haemoglobin and need for blood transfusion in simultaneous bilateral
      total knee replacement surgeries performed without the use of tourniquet.

PMID- 29594529
TI  - Ferutinin Induces Membrane Depolarization, Permeability Transition Pore
      Formation, and Respiration Uncoupling in Isolated Rat Liver Mitochondria by
      Stimulation of Ca2+-Permeability.
AB  - It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9
      en), isolated from the plant Ferula tenuisecta, considerably increases the
      permeability of artificial and cellular membranes to Ca2+-ions and produces
      apoptotic cell death in different cell lines in a mitochondria-dependent manner.
      The present study was designed for further evaluation of the mechanism(s) of
      mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our
      findings provide evidence for ferutinin at concentrations of 5-27 uM to decrease
      state 3 respiration and the acceptor control ratio in the case of
      glutamate/malate as substrates. Ferutinin alone (10-60 uM) also dose-dependently
      dissipated membrane potential. In the presence of Ca2+-ions, ferutinin (10-60 uM)
      induced considerable depolarization of the inner mitochondrial membrane, which
      was partially inhibited by EGTA, and permeability transition pore formation,
      which was diminished partly by cyclosporin A, and did not influence markedly the
      effect of Ca2+ on mitochondrial respiration. Ruthenium Red, a specific inhibitor
      of mitochondrial calcium uniporter, completely inhibited Ca2+-induced
      mitochondria swelling and membrane depolarization, but did not affect markedly
      the stimulation of these Ca2+-dependent processes by ferutinin. We concluded that
      the mitochondrial effects of ferutinin might be primarily induced by stimulation
      of mitochondrial membrane Ca2+-permeability, but other mechanisms, such as
      driving of univalent cations, might be involved.

PMID- 29594530
TI  - Parental awareness of testicular torsion amongst Irish parents.
AB  - PURPOSE: Testicular torsion is the most concerning underlying cause of acute
      scrotal pain that can lead to loss of the affected testicle. Whether a torted
      testicle can be salvaged surgically is directly affected by prompt presentation
      and diagnosis. This study aims to evaluate the awareness of testicular torsion
      amongst Irish parents and evaluate their response to a potential torsion.
      METHODS: An anonymous questionnaire was distributed to parents attending general
      paediatric clinics and an acute paediatric unit in two paediatric tertiary
      referral centres. SPSS statistical analysis software was used to perform
      multivariant analysis of the data. RESULTS: There were 242 completed surveys.
      Fifty-six percent of responders had an awareness of torsion. In the event of an
      episode of severe testicular pain parents who were aware of testicular torsion
      were 4 times more likely to present immediately than those who had no awareness
      of torsion (OR 4.2, 95% CI 1.4-12.2, P < 0.01), and those who identified
      correctly the critical timeframe were 3 times more likely to present immediately
      than those who did not (OR 3.0, 95% CI 0.85-10.8, P = 0.08). Of those parents
      with boys only 11% had discussed what to do in the event of acute scrotal pain.
      CONCLUSIONS: Education of this topic to the general Irish population and in
      particular to parents and young males is not established. Both knowledge of
      testicular torsion and awareness of the urgency in presentation are factors that
      determine parents promptness in seeking medical attention for their child in the
      setting of acute scrotal pain.

PMID- 29594531
TI  - Determination of subnanomolar levels of mercury (II) by using a graphite paste
      electrode modified with MWCNTs and Hg(II)-imprinted polymer nanoparticles.
AB  - Mercury ion-imprinted polymer nanoparticles (Hg-IP-NPs) were synthesized via
      precipitation polymerization by using itaconic acid as a functional monomer. A
      carbon paste electrode was impregnated with the synthesized Hg-IP-NPs and MWCNTs
      to obtain a highly sensitive and selective electrode for determination of Hg(II).
      Mercury ion is first accumulated on the electrode surface via an open circuit
      procedure. After reduction of Hg(II) ions to its metallic form at a negative pre
      potential, square wave anodic stripping voltammetry was applied to generate the
      electrochemical signal. The high affinity of the Hg-IP-NPs for Hg(II) was
      substantiated by comparing of the signals of electrodes with imprinted and non
      imprinted polymer. The beneficial effect of MWCNTs on the voltammetric signal is
      also demonstrated. Under the optimized conditions and at a typical working
      potential of +0.05 V (vs. Ag/AgCl), the electrode has a linear response in the
      0.1-20 nmol L-1 Hg(II) concentration range and a 29 pM detection limit. The
      electrochemical sensitivity is as high as 1441 A.M-1.cm-2 which is among the best
      values known. The electrode was applied to the determination of Hg(II) in water
      samples. Graphical abstract Schematic representation of the sensor electrode
      modified with mercury-imprinted polymer nanoparticles, and the recognition and
      voltammetric determination steps.

PMID- 29594532
TI  - Inner filter effect based fluorometric determination of the activity of alkaline
      phosphatase by using carbon dots codoped with boron and nitrogen.
AB  - Boron and nitrogen codoped carbon dots functionalized with cyclodextrin (beta-CD
      N/B-C-dots) were obtained from beta-cyclodextrin. The material displays strong
      fluorescence (with excitation/emission peak wavelengths of 400/500 nm) and was
      characterized by UV-vis, transmission electron microscopy and FTIR. If the
      substrate p-nitrophenylphosphate is enzymatically cleaved by alkaline phosphatase
      (ALP), a yellow product is formed whose absorption overlaps the excitation
      spectrum of the beta-CD-N/B-C-dots. Hence, fluorescence is reduced due to an
      inner filter effect. In additon, the beta-CD cavity offers a pocket for substrate
      recognition. The findings were used to design a method for the determination of
      the activity of ALP. It has a working range that extends from 0.003 to 5.5 U.L-1,
      with a 0.3 mU.L-1 detection limit. The method is fast, simple, inexpensive, and
      highly sensitive and selective. Graphical abstract Schematic of an inner filter
      effect based probe for alkaline phosphatase based on the use boron and nitrogen
      co-doped carbon dots (N/B-C-dots) modified with beta-cyclodextrin (beta-CD).
      PNPP: p-Nitrophenylphosphate; PNP: p-Nitrophenol anion.

PMID- 29594533
TI  - Determination of RNase H activity via real-time monitoring of target-triggered
      rolling circle amplification.
AB  - The authors describe a method for real-time monitoring of the activity of
      ribonuclease H (RNase H). It is based on target-triggered rolling circle
      amplification (RCA). It utilizes a specially designed primer that contains a RNA
      sequence in the center and an amino group at the 3'-end. In the absence of RNase
      H, the primer when hybridized to a circular DNA template is not extended by DNA
      polymerase due to the amino group at the 3'-end. In contrast, the presence of
      RNase H specifically degrades the RNA sequence of the primer hybridized to the
      circular DNA template. This results in the conversion of the 3'-amino group to a
      3'-hydroxy group and thereby enables the extension reaction promoted by DNA
      polymerase. This, consequently, leads to efficient RCA producing a long
      concatenated DNA strand. Its generation can be monitored in real-time by using
      the fluorescent dye SYBR green II which is specific for single-stranded DNA.
      Based on this RNase H-triggered RCA, RNase H activity can be selectively
      determined at levels as low as 0.019 U.mL-1 with a total assay time of <5 min.
      The diagnostic capability of this assay was demonstrated by monitoring the
      activity of RNase H in tumor cells. Graphical abstract Schematic of real-time
      monitoring of ribonuclease H (RNase H) activity based on target-triggered rolling
      circle amplification (RCA). RNase H that degrades RNA in primer, converts 3'
      amino group to 3'-hydroxy group, which promotes RCA with fluorescence enhancement
      of the probe SYBR green II.

PMID- 29594534
TI  - Magnetic mesoporous polymelamine-formaldehyde resin as an adsorbent for endocrine
      disrupting chemicals.
AB  - A magnetic mesoporous poly(melamine-formaldehyde) composite (Fe3O4-mPMF) was
      prepared via grafting poly(melamine-formaldehyde) onto the surface of amino
      functionalized magnetite (Fe3O4) nanoparticles. The material was characterized by
      scanning electron micrography, transmission electron microscopy, X-ray
      diffraction, Fourier transform-infrared spectroscopy, nitrogen adsorption
      desorption isotherms, and thermogravimetric analysis. It has a large surface
      area, a typical mesoporous structure, and a high thermal stability. It was
      employed as a magnetic sorbent for the solid phase extraction of the following
      endocrine disrupting chemicals (EDCs): Bisphenol A, 4-tert-butylphenol, 4-tert
      octylphenol and nonylphenol. The EDCs were then quantified by HPLC. Under the
      optimized conditions, the response to the EDCs is linear in the range of 0.5-100
      ng.mL-1, and the limits of detection are 0.02-0.1 ng.mL-1. The high adsorption
      capability of the Fe3O4-mPMF is mainly attributed to multiple interactions
      including pi-stacking, hydrogen bonding, and hydrophobic interactions. The method
      was applied to the extraction of EDCs from spiked river water and bottled juice
      samples. The results demonstrated that the Fe3O4-mPMF is an efficient adsorbent
      for the extraction of organic compounds with large conjugated pi-system, plenty
      of hydrogen-bonding sites, and strong hydrophobicity. Graphical abstract A
      magnetic mesoporous polymelamine-formaldehyde composite (Fe3O4-mPMF) was prepared
      and employed as a magnetic sorbent for the solid phase extraction of endocrine
      disrupting chemicals from river water and bottled juice samples prior to high
      performance liquid chromatographic analysis.

PMID- 29594535
TI  - Amperometric determination of hydroquinone and catechol using a glassy carbon
      electrode modified with a porous carbon material doped with an iron species.
AB  - A porous carbon material doped with an iron species (Fe/PC) was prepared by
      carbonizing a mixture of zeolitic imidazolate framework-8 in the presence of
      iron(II) ions. The resulting material was characterized by X-ray diffraction,
      nitrogen adsorption isotherms, transmission electron microscopy, and by Raman and
      X-ray photoelectron spectroscopy. Fe/PC was the deposited on the surface of
      glassy carbon electrode (GCE) to obtain a sensor for amperometric determination
      of phenolic compounds. The unique catalytic activity, good electrical
      conductivity and hierarchical structure of the Fe/PC composite results in good
      electrooxidative activity towards hydroquinone (HQ; typically at 44 mV) and
      catechol (CC; typically at 160 mV). Under optimal conditions, the amperometric
      responses are linear in the range from 0.1 to 120 MUmol . L-1 for HQ, and from
      1.0 to 120 MUmol . L-1 for CC. The respective detection limits are 14 and 33 nmol
      . L-1. The sensor is highly selective against potential interferents and was
      successfully applied to the determination of HQ and CC contents in (spiked) water
      samples. Graphical abstract An amperometric sensor for phenolic compounds was
      constructed by using a metal-organic framework derived iron doped porous carbon
      material.

PMID- 29594536
TI  - Use of black-bone MRI in the diagnosis of the patients with posterior
      plagiocephaly.
AB  - PURPOSE: Ionising radiation exposure is especially harmful to brain development.
      The purpose of this study was to evaluate whether black-bone (BB) magnetic
      resonance imaging (MRI), a non-ionising imaging method, offers an alternative to
      ionising imaging methods such as computed tomography (CT) in the examination of
      cranial deformities. METHODS: From 2012 to 2014, a total of 408 children were
      referred to the Craniofacial Centre at the Helsinki University Hospital for
      further examination due to flatness of the posterior skull. Fifteen of these
      patients required further diagnostic imaging. To avoid ionising radiation, we
      used an MRI protocol that included sequences for evaluation of both brain anatomy
      and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation
      algorithm was developed to facilitate the visualisation. Two patients with
      scaphocephaly were included in the study to confirm the ability to differentiate
      synostosis with BB-MRI. RESULTS: We obtained informative 3D images using BB-MRI.
      Seven patients (7/15, 46.7%) had plagiocephaly on the right side and seven on the
      left side (7/15, 46.7%). One patient (1/15, 6.7%) had symmetric posterior
      flatness affecting both sides. Neither structural nor signal-intensity
      alterations of the brain were detected in visual analysis. CONCLUSION: BB-MRI
      provides an alternative to CT when imaging craniofacial deformities. BB-MRI
      provides not only high-quality 3D-reconstructed imaging of the bony structures
      and sutures but also information on brain structure in one imaging session. With
      further development, this method could replace ionising radiation-based methods
      in analysing deformities of the skull.

PMID- 29594537
TI  - A nanoporous carbon material coated onto steel wires for solid-phase
      microextraction of chlorobenzenes prior to their quantitation by gas
      chromatography.
AB  - A nanoporous carbon material was synthesized by heating potassium citrate without
      using a template or an activating agent. It is shown to represent a viable
      coating for use in solid-phase microextraction. The material is thermally stable
      and mainly consists of amorphous sheets of sp2-bonded carbon. It has an extensive
      pore structure and a surface area as large as 1236 m2.g-1. The nanoporous carbon
      was deposited on the surface of steel wires, and the resulting fibers were
      applied to the extraction of trace levels of chlorobenzenes in water samples.
      Following extraction by absorbing, the chlorobenzenes were quantified by gas
      chromatograph in combination with electron capture detection. Extraction
      temperature and time, and desorption temperature were optimized (80  degrees C,
      10 min and 310  degrees C). Under optimized conditions, the calibration plots are
      linear in the following concentration ranges: 2.5 to 100 ng.L-1
      (pentachlorobenzene), 5 to 200 ng.L-1 (1,2,3,4-tetrachlorobenzene), 10 to 100
      ng.L-1 (hexachlorobenzene) and 10 to 500 ng.L-1 (1,2,3-trichlorobenzene, 1,2,4
      trichlorobenzene, 1,3,5-trichlorobenzene). Other figures of merit include (a)
      high enrichment factors (8324 to 9920), (b) low limits of detection (0.10-1.03
      ng.L-1), and (c) good reproducibility (relative standard deviations including
      intra-day and inter-day with a single fiber and fiber-to-fiber were below 6.4% at
      a mixed concentration level of 2.5, 5, and 10 ng.L-1 respectively in ultra
      water). This method was successfully applied to the determination of
      chlorobenzenes in (spiked) lake waters where it gave recoveries between 82.3% and
      104.5%. Graphical abstract A nanoporous carbon material was synthesized by
      heating potassium citrate without using a template or an activating agent and
      used as a viable coating of solid-phase microextraction for chlorobenzenes.

PMID- 29594539
TI  - Expression of Concern: Magnetic mesoporous polymelamine-formaldehyde resin as an
      adsorbent for endocrine disrupting chemicals.
AB  - The Editor-in-Chief is issuing an editorial expression of concern regarding the
      article Microchim Acta (2018) 185: 19.

PMID- 29594538
TI  - A review on chemiresistive room temperature gas sensors based on metal oxide
      nanostructures, graphene and 2D transition metal dichalcogenides.
AB  - Room-temperature (RT) gas sensing is desirable for battery-powered or self
      powered instrumentation that can monitor emissions associated with pollution and
      industrial processes. This review (with 171 references) discusses recent advances
      in three types of porous nanostructures that have shown remarkable potential for
      RT gas sensing. The first group comprises hierarchical oxide nanostructures
      (mainly oxides of Sn, Ni, Zn, W, In, La, Fe, Co). The second group comprises
      graphene and its derivatives (graphene, graphene oxides, reduced graphene oxides,
      and their composites with metal oxides and noble metals). The third group
      comprises 2D transition metal dichalcogenides (mainly sulfides of Mo, W, Sn, Ni,
      also in combination with metal oxides). They all have been found to enable RT
      sensing of gases such as NOx, NH3, H2, SO2, CO, and of vapors such as of acetone,
      formaldehyde or methanol. Attractive features also include high selectivity and
      sensitivity, long-term stability and affordable costs. Strengths and limitations
      of these materials are highlighted, and prospects with respect to the development
      of new materials to overcome existing limitations are discussed. Graphical
      Abstract The review summarizes the most significant progresses related to room
      temperature gas sensing by using hierarchical oxide nanostructures, graphene and
      its derivatives and 2D transition metal dichalcogenides, highlighting the
      peculiar gas sensing behavior with enhanced selectivity, sensitivity and long
      term stability.

PMID- 29594540
TI  - FePO4 embedded in nanofibers consisting of amorphous carbon and reduced graphene
      oxide as an enzyme mimetic for monitoring superoxide anions released by living
      cells.
AB  - FePO4 is biocompatible and can act as a kind of promising enzyme mimetic.
      Unfortunately, the electrical conductivity of FePO4 is poor. In order to enhance
      its conductivity, FePO4 was embedded into nanofibers consisting of amorphous
      carbon and reduced graphene oxide (rGO) by an electrospinning technique. As a
      sensing material for monitoring superoxide anion (O2*-) and typically operated at
      0.5 V (vs. SCE), it displays high sensitivity (9.6 MUA?MUM-1?cm-2), a low
      detection limit (9.7 nM at S/N = 3), a wide linear response range (10 nM to 10
      MUM), and fast response (1.6 s). Due to its low detection limit and fast
      response, the sensor in our perception has a large potential for detecting
      superoxide anions released by HeLa cancer cells. Graphical abstract Schematic of
      the microstructure of FePO4/C and FePO4/rGO-C nanofibers, a photograph of cancer
      cells (HeLa), and the electrochemical response towards O2-* of the sensor.

PMID- 29594541
TI  - Ratiometric detection of hydroxy radicals based on functionalized europium(III)
      coordination polymers.
AB  - A ratiometric fluorescent probe is described that is based on a functionalized
      europium(III) coordination polymer (Eu/DPA-TA). It can be fabricated by using
      dipicolinic acid (DPA) as a bridging ligand (to sensitize the Eu3+ fluorescence)
      and terephthalic acid (TA) acting as a functional ligand to recognize the hydroxy
      radical (*OH). The quenching of Eu3+ fluorescence (measured at
      excitation/emission wavelengths of 288/615 nm) by water is strongly reduced in
      the presence of TA. This leads to a significant enhancement in the emission
      lifetime and intensity of Eu3+. Upon the addition of *OH, the fluorescence of
      Eu/DPA-TA showed ratiometric changes in that the TA sensitized fluorescence
      (peaking at 445 nm) is switched on, while the plain Eu3+ fluorescence (peaking at
      615 nm) decreases. This finding led to a method for the ratiometric (2
      wavelength) detection of OH with a 0.5 MUM detection limit. The method also
      allows OH to be detected with bare eyes at OH concentrations as low as 10 MUM. In
      our perception, this study paves the way towards the design of new functionalized
      lanthanide coordination polymers for fluorometric assays and biomedical imaging.
      Graphical abstract Schematic of a ratiometric fluorescent assay for the detection
      of hydroxy radical (*OH) based on the use of a europium(III)/dipicolinic acid
      coordination polymer (Eu/DPA CP) functionalized with terephthalic acid (TA). A
      gradual color change from red to blue can be observed and correlated to *OH
      concentrations.

PMID- 29594542
TI  - A hyper-cross linked polymer as an adsorbent for the extraction of chlorophenols.
AB  - A porous material (polytriphenylamine; PTPA) was synthesized by using
      triphenylamine as the monomer and dimethoxymethane as the cross-linker. PTPA was
      characterized by Fourier infrared spectrometry, X-ray diffraction measurements,
      scanning electron microscopy and N2 adsorption-desorption isotherms. The PTPA has
      a spherical-shape morphology and relatively high specific surface area. It is
      shown to be a viable adsorbent for solid phase extraction of 3-chlorophenol, 2,3
      dichlorophenol, 2,4-dichlorophenol and 2,4.6-trichlorophenol prior to their
      determination by high performance liquid chromatography-mass spectrometry. Under
      the optimized conditions, recoveries from spiked samples are in the range from
      92.5% to 106.3%. The limits of detection range from 0.03 to 0.3 ng mL-1 (at an
      S/N ratio of 3) in case of bottled juice, and from 0.03 to 0.1 ng g-1 in case of
      tomato samples. The enrichment factors for the four analytes are in the range of
      127-183 for bottle juice, and from 110-150 for tomatos. Response is linear in the
      range of 1.0 to 40.0 ng mL-1 for juice, and 0.3-40.0 ng g-1 for tomatos. The
      relative standard deviations for the determination of the chlorophenols at 20 ng
      mL-1 in bottled beverage, and 20 ng g-1 in tomatos are lower than 5.7%. Graphical
      abstract A polytriphenylamine polymer (PTPA) was prepared by using an external
      cross-linker method with triphenylamine as monomer and dimethoxymethane as cross
      linker, and it was used as an adsorbent to extract chlorophenols from juice and
      vegetable samples.

PMID- 29594543
TI  - Switched voltammetric determination of ractopamine by using a temperature
      responsive sensing film.
AB  - This study describes an electrochemical sensor for the animal growth promoter
      ractopamine. The method is based on the use of a glassy carbon electrode (GCE)
      modified with a temperature-responsive sensing film composed of reduced graphene
      oxide, C60 fullerene, and the temperature-sensitive polymer poly(2-(2
      methoxyethoxy)ethyl methacrylate) (PMEO2MA). The modified GCE was characterized
      by scanning electron microscopy and electrochemical impedance spectroscopy. A
      large oxidation peak current can be observed (maximum typically at 0.57 V vs.
      Ag/AgCl) when the temperature is raised to above the lower critical solution
      temperature of PMEO2MA. This peak disappears at lower temperature. Under optimum
      conditions, the sensor has a detection range for ractopamine from 0.1 to 3.1 MUM,
      with an 82 nM detection limit. The method was successfully applied to the
      determination of ractopamine in spiked pork samples. Graphical abstract Schematic
      presentation of the reversible, temperature-controlled "on/off" electrochemical
      behavior of ractopamine at a glassy carbon electrode modified with a film
      composed of reduced graphene oxide (rGO), C60 fullerene and the poly(2-(2
      methoxyethoxy)ethyl methacrylate) (PMEO2MA).

PMID- 29594544
TI  - Voltammetric determination of the Escherichia coli DNA using a screen-printed
      carbon electrode modified with polyaniline and gold nanoparticles.
AB  - The authors describe an electrochemical assay for fast detection of Escherichia
      coli (E. coli). It is based on a dual signal amplification strategy and the use
      of a screen-printed carbon electrode (SPCE) whose surface was modified with a
      polyaniline (PANI) film and gold nanoparticles (AuNPs) via cyclic voltammetry
      (CV). In the next step, avidin was covalently immobilized on the PANI/AuNP
      composite on the SPCE surface. Subsequently, the biotinylated DNA capture probe
      was immobilized onto the PANI/AuNP/avidin-modified SPCE by biotin-avidin
      interaction. Then, DNA of E.coli, digoxigenin-labeled DNA detector probe and anti
      digoxigenin-labeled horseradish peroxidase (HRP) were placed on the electrode.
      3,3',5,5'-Tetramethylbenzidine (TMB) and H2O2 solution were added and the CV
      electrochemical signal was generated at a potential of -0.1 V (vs. Ag/AgCl) and a
      scan rate 50 mV.s-1. The assay can detect 4 * 106 to 4 CFU of E. coli without DNA
      amplification. The biosensor is highly specific over other pathogens including
      Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus
      haemolyticus and Pseudomonas aeruginosa. It can be concluded that this genosensor
      has an excellent potential for rapid and accurate diagnosis of E.coli inflicted
      infections. Graphical Abstract Schematic of an electrochemical E. coli genosensor
      based on sandwich assay on a polyaniline/gold nanoparticle-modified screen
      printed carbon electrode (SPCE). The biosensor can detect 4 * 106 to 4 CFU of E.
      coli without DNA amplification.

PMID- 29594545
TI  - Lower back and neck pain among dentistry students: a cross-sectional study in
      dentistry students in Northern Greece.
AB  - INTRODUCTION: Dentistry students and dentists comprise a unique group of
      professionals, whose everyday professional activity requires long hours of
      standing and working in a position considered unhealthy for the lower back and
      neck. Our aim was to explore the factors involved in the appearance of low back
      and neck pain in dentistry students as well as the impact of the pain on the
      students' professional and everyday activities. MATERIALS AND METHODS: A
      questionnaire was given to all dentistry students of the 4th and 5th year of our
      university. The questionnaire included 43 questions regarding demographic data,
      history (spinal injury, other comorbidities), daily activities (exercise,
      smoking, alcohol and caffeine consumption, use of cell phone), professional
      activities (length and type of dental work), pattern and intensity of pain, and
      personal pain evaluation. A statistical analysis of the gathered data was
      performed. RESULTS: All students having suffered a spinal trauma or indicating
      any other comorbidity that could cause severe pain of the spine were excluded
      from the study. Fifty-five students (21 male, 34 female) were included. Our data
      showed that increased alcohol consumption and prolonged use of cell phone were
      connected to increased levels of pain. The students reported that the most
      frequent onset of pain was 1 h after starting to work in a standing position,
      while the majority believed that their working habits were involved in the
      appearance and the intensity of neck and low-back pain. CONCLUSION: Our findings
      indicate that among dentistry students appears to be a causative relationship
      between their professional activities and the experienced spinal pain. These
      findings may be useful in a possible future restructuring of the educational
      program in dental schools, as well as in improving the ergonomics of dentistry
      working units.

PMID- 29594546
TI  - Vortex assisted solid-phase extraction of lead(II) using orthorhombic nanosized
      Bi2WO6 as a sorbent.
AB  - Nanosized single crystal orthorhombic Bi2WO6 was synthesized by a hydrothermal
      method and used as a sorbent for vortex assisted solid phase extraction of
      lead(II). The crystal and molecular structure of the sorbent was examined using
      XRD, Raman, SEM and SEM-EDX analysis. Various parameters affecting extraction
      efficiency were optimized by using multivariate design. The effect of diverse
      ions on the extraction also was studied. Lead was quantified by flame atomic
      absorption spectrometry (FAAS). The recoveries of lead(II) from spiked samples
      (at a typical spiking level of 200-400 ng.mL-1) are >95%. Other figures of merit
      includes (a) a detection limit of 6 ng.mL-1, (b) a preconcentration factor of 50,
      (c) a relative standard deviation of 1.6%, and (d) and adsorption capacity of 6.6
      mg.g-1. The procedure was successfully applied to accurate determination of lead
      in (spiked) pomegranate and water samples. Graphical abstract Nanosized single
      crystal orthorhombic Bi2WO6 was synthesized and characterized by a hydrothermal
      method and used as a sorbent for vortex assisted solid phase extraction of
      lead(II). The procedure was successfully applied to accurate determination of
      lead in (spiked) pomegranate and water samples.

PMID- 29594547
TI  - A molecularly imprinted polymer placed on the surface of graphene oxide and doped
      with Mn(II)-doped ZnS quantum dots for selective fluorometric determination of
      acrylamide.
AB  - A polymer imprinted with acrylamide (AM-MIP) was synthesized on the surface of
      graphene oxide by surface polymerization of propionamide (serving as a dummy
      template), methacrylic acid (as the functional monomer) and ethylene glycol
      dimethacrylate (the cross-linker). ZnS quantum dots (QDs) doped with Mn(II) ions
      were added to the AM-MIP to act as fluorescence source. The AM-MIP was
      characterized by infrared spectroscopy, scanning electron microscopy and X-ray
      powder diffraction, suggesting that the imprinted layer was successfully grafted
      onto graphene oxide. The fluorescence of the doped QDs is quenched when loading
      the AM-MIP with acrylamide (AM), and the quenching effect is much stronger than
      the non-imprinted polymer (AM-NIP). Quenching follows Stern-Volmer kinetics. The
      combination of imprinting and fluorometric detection offer AM-IIP capability to
      accumulate trace AM before direct determination, omitting desorption and
      separation or other methods. The excitation and emission spectra of AM-MIP peak
      at 325 nm and 601 nm, respectively. Under optimal conditions, fluorescence drops
      linearly in the 0.5-60 MUmol.L-1 acrylamide concentration range, and the
      detection limit is 0.17 MUmol.L-1. The method has been applied to the
      determination of AM in spiked water samples and gave recoveries in the range from
      100.2 to 104.5%, with relative standard deviations in the 1.9 to 3.9% range. In
      our perception, the AM-MIP presented here is a promising fluorescent probe for
      the detection of trace acrylamide in food. Graphical abstract Schematic of the
      preparation of graphene oxide coated with a molecularly imprinted polymer doped
      with Mn(II)-doped ZnS quantum dots. Propionamide serves as a dummy template.
      Acrylamide acts as a quencher of fluorescence, and this effect is used for its
      selective fluorometric determination.

PMID- 29594548
TI  - Psychiatric co-morbidity, distress, and use of psycho-social services in adult
      glioma patients-a prospective study.
AB  - BACKGROUND: Distress impacts the daily life of glioma patients. This study
      explored its course over time and the usage of psychosocial care. METHODS: A
      consecutive sample of glioma patients completed the Hospital Anxiety and
      Depression Scale to assess distress levels at admission to the hospital (t1),
      before discharge (t2), after 3 months (t3), and after 6 months (t4). They were
      interviewed with the Structured Clinical Interview for DSM-IV to ascertain
      psychiatric disorders at t2. Psycho-oncological care in the hospital was
      determined with the Hospital Information System, and the use of outpatient
      treatment was evaluated with the Health Care Usage Questionnaire at t4. We
      compared the percentages of elevated distress, psychiatric co-morbidity, and care
      usage between men and women. RESULTS: During the study period, 37 patients were
      enrolled. Nineteen percent of the patients were diagnosed with a psychiatric
      disorder. The percentages of patients with elevated distress were 56, 59, 39, and
      40% at t1, t2, t3, and t4, respectively. Participants who did not survive the 6
      months presented with higher levels of distress. In the hospital, 14% of those
      with elevated distress were visited by a psycho-oncologist. In the outpatient
      setting, 43% of those with elevated distress visited a neuro-psychiatrist, and
      14% went to a psychotherapist. There was no evidence for an effect of gender on
      psychiatric co-morbidity, distress, or care use. CONCLUSIONS: A significant
      proportion of glioma patients report elevated distress during the hospital stay
      and thereafter. Only a fraction of them receive mental health care.

PMID- 29594549
TI  - Porphyrin based porous organic polymer modified with Fe3O4 nanoparticles as an
      efficient adsorbent for the enrichment of benzoylurea insecticides.
AB  - Porphyrin-based porous organic polymers (P-POPs) are amorphous polymers linked by
      strong covalent bonds between the porphyrin subunits that act as building blocks.
      The authors describe a magnetic P-POP that possesses high surface area, a highly
      porous structure, and strong magnetism. The MP-POP was employed as a magnetic
      sorbent for the extraction of benzoylurea insecticides from cucumber and tomato
      samples prior to their determination by HPLC. The sorbent has a typical sorption
      capacity of 1.90-2.00 mg?g-1. The method exhibits a good linear range (0.8-160
      ng.g-1), low limits of detection (0.08-0.2 ng.g-1), and high method recoveries
      (81.8-103.5%) for cucumber and tomato samples. The MP-POP has different
      adsorption capabilities for the benzoylurea insecticides, phenylurea herbicides
      and phenols compounds, and the adsorption mechanism is found to be based on pi
      stacking, hydrogen-bonding, and hydrophobic interactions. Graphical abstract A
      novel magnetic porphyrin-based porous organic polymer was fabricated and used as
      the adsorbent for the efficient extraction of benzoylurea insecticides.

PMID- 29594550
TI  - Voltammetric sensing of dopamine based on a nanoneedle array consisting of
      NiCo2S4 hollow core-shells on a nickel foam.
AB  - An array consisting of homogeneous NiCo2S4 hollow core-shell nanoneedles was
      fabricated and is shown to enable sensitive electrochemical determination of
      dopamine (DA). The array was grown directly on a nickel foam (NF) substrate by a
      two-step hydrothermal process. The hierarchical nanoarray consists of a
      homogeneous NiCo2S4 nanoneedle core and a NiCo2S4 nanosheet shell. A 3
      dimensional micro/nano structure is formed due to the presence of the micropores
      of the NF. The electrode was characterized by scanning electron microscopy,
      transmission electron microscopy, X-ray diffraction and X-ray photoelectron
      spectroscopy. Compared to a plain NF electrode, the NiCo2S4-modified NF electrode
      displays higher electrocatalytic activity for the oxidation of DA by differential
      pulse voltammetry (DPV). The sensor, best operated at a typical working voltage
      of 134 mV (vs. saturated calomel electrode), has a linear response in the 0.5-100
      MUM DA concentration range and a 0.2 MUM detection limit (at S/N = 3). The
      electrode is selective over ascorbic acid and uric acid. Graphical abstract
      Schematic presentation of an electrochemical sensor for selective determination
      of dopamine based on the use of a homogeneous NiCo2S4 hollow core-shell
      nanoneedle array on nickel foam.

PMID- 29594551
TI  - Pair-matched patient-reported quality of life and early oncological control
      following focal irreversible electroporation versus robot-assisted radical
      prostatectomy.
AB  - PURPOSE: The design, conduct and completion of randomized trials for curative
      prostate cancer (PCa) treatments are challenging. To evaluate the effect of robot
      assisted radical prostatectomy (RARP) versus focal irreversible electroporation
      (IRE) on patient-reported quality of life (QoL) and early oncological control
      using propensity-scored matching. METHODS: Patients with T1c-cT2b significant PCa
      (high-volume ISUP 1 or any 2/3) who received unifocal IRE were pair-matched to
      patients who received nerve-sparing RARP. Patient-reported outcomes were
      prospectively assessed using the Expanded Prostate Cancer Index Composite (EPIC),
      AUA symptom score and Short Form of Health Survey (SF-12) physical and mental
      components. Oncological failure was defined as biochemical recurrence (RARP) or
      positive follow-up biopsies (IRE). Generalized mixed-effect models were used to
      compare IRE and RARP. RESULTS: 50 IRE patients were matched to 50 RARP patients
      by propensity score. IRE was significantly superior to RARP in preserving pad
      free continence (UC) and erections sufficient for intercourse (ESI). The absolute
      differences were 44, 21, 13, 14% for UC and 32, 46, 27, 22% for ESI at 1.5, 3, 6,
      and 12 months, respectively. The EPIC summary scores showed no statistically
      significant differences. Urinary symptoms were reduced for IRE and RARP patients
      at 12 months, although IRE patient initially had more complaints. IRE patients
      experienced more early oncological failure than RARP patients. CONCLUSIONS: These
      data demonstrated the superior preservation of UC and ESI with IRE compared to
      RARP up to 12 months after treatment. Long-term oncological data are warranted to
      provide ultimate proof for or against focal therapy.

PMID- 29594552
TI  - Determination of protein kinase A activity and inhibition by using hydroxyapatite
      nanoparticles as a fluorescent probe.
AB  - The authors describe a fluorometric method for the determination of the activity
      and inhibition of protein kinase A (PKA). In the presence of ATP, PKA catalyzes
      the transfer of phosphate groups from ATP to a peptide, and the generated
      phosphorylated peptide quenches the fluorescence (measured at excitation/emission
      peaks of 340/440 nm) of the hydroxyapatite nanoparticles (HAP-NPs). A linear
      logarithmic relationship of PKA concentrations with fluorescence intensity in the
      range from 1 to 50 U.L-1 was obtained, and the lower limit of detection (LOD) is
      0.5 U.L-1. This is much lower than LODs reported in the literature. The PKA
      inhibitor H-89 was studied, and the inhibition plot has a sigmoidal shape with a
      half-maximal inhibitory concentration of around 750 nM of H-89. At a 4.5 nM level
      of H-89, fluorescence of HAP-NPs fell to levels of no PKA controls, demonstrating
      that the assay is a viable tool to screen for kinase inhibitors. An assay with
      Hela cell lysates in combination with forskolin (an activator of adenylyl
      cyclase) and IBMX (a phosphodiesterase inhibitor used to activate the cellular
      activity of PKA) resulted in decreased fluorescence of HAP-NPs. This suggests
      that the assay can be applied for testing in vitro cell kinase activity. In our
      perception, this method will enable high-throughput screening for kinase-related
      drugs and fluorometric enzymatic detection in various areas. Graphical abstract
      Fluorescence assay based on hydroxyapatite nanoparticles (HAP) fluorescence
      quenching was developed for analysis of the activity and inhibition of protein
      kinase A (PKA).

PMID- 29594553
TI  - A new kind of highly sensitive competitive lateral flow immunoassay displaying
      direct analyte-signal dependence. Application to the determination of the
      mycotoxin deoxynivalenol.
AB  - A new kind of competitive immunochromatographic assay is presented. It is based
      on the use of a test strip loaded with (a) labeled specific antibodies, (b) a
      hapten-protein conjugate at the control zone, and (c) antibodies interacting with
      the specific antibodies in the analytical zone. In the case where a sample does
      not contain the target antigen (hapten), all labeled antibodies remain in the
      control zone because of the selected ratio of reactants. The analytical zone
      remains colorless because the labeled antibodies do not reach it. If an antigen
      is present in the sample, it interferes with the binding of the specific
      antibodies in the control zone and knocks them out. Some of these antibodies pass
      the control zone to form a colored line in the analytical zone. The intensity of
      the color is directly proportional to the amount of the target antigen in the
      sample. The assay has an attractive feature in that an appearance in coloration
      is more easily detected visually than a decoloration. Moreover, the onset of
      coloration is detectable at a lower concentration than a decoloration. The new
      detection scheme was applied to the determination of the mycotoxin
      deoxynivalenol. The visual limit of detection is 2 ng.mL-1 in corn extracts (35
      ng per gram of sample). With the same reagents, this is lower by a factor of 60
      than the established test strip. The assay takes only 15 min. This new kind of
      assay has wide potential applications for numerous low molecular weight analytes.
      Graphical abstract Competitive immunochromatography with direct analyte-signal
      dependence is proposed. It provides a 60-fold decrease of the detection limit for
      mycotoxin deoxynivalenol. The analyte-antibody-label complexes move along the
      immobilized antigen (control zone) and bind with anti-species antibodies (test
      zone).

PMID- 29594554
TI  - Microextraction of polycyclic aromatic hydrocarbons by using a stainless steel
      fiber coated with nanoparticles made from a porous aromatic framework.
AB  - A porous aromatic framework of type PAF-6 was synthesized and explored as a
      coating onto a steel wire for using in solid-phase microextraction of polycyclic
      aromatic hydrocarbons (PAHs), phthalate plasticizers, and n-alkanes. The
      extraction temperature, extraction time, salt concentration, agitation speed,
      desorption temperature, and desorption time were optimized. This method for SPME
      resulted in the enrichment factors ranging from 122 to 1090 for PAHs
      (naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene,
      pyrene), from 122 to 271 for plasticizers (diisobutyl phthalate, dibutyl
      phthalate, benzyl butyl phthalate, dicyclohexyl phthalate), and from 9 to 113 for
      n-alkanes (n-undecane, n-dodecane, n-tridecane, n-tetradecane, n-pentadecane, n
      hexadecane, n-octadecane and n-eicosane). The good extraction of the PAHs is
      assumed to be due to their pi-stacking interaction and hydrophobic effect. The
      PAF-6 coated fibers are durable and can be reused more than 100 times without
      significant loss of extraction performance. In combination with GC-MS detection,
      the method has limits of detection in the range from 0.8 to 4.2 ng L-1 in case of
      PAHs. The relative standard deviations for five replicate determinations of the
      PAHs by using one fiber are in the range from 5.2 to 8.5%. When using different
      fibers, they range from 7.1 to 9.6%. The recoveries of PAHs from water samples at
      a spiking level of 20 ng L-1 are in the range from 89.5 to 103.1%, with relative
      standard deviations ranging from 4.0 to 9.3%. Graphical abstract A porous
      aromatic framework of type PAF-6 was synthesized and used as a novel coating for
      the solid-phase microextraction of polycyclic aromatic hydrocarbons prior to
      their determination by gas chromatography with mass spectrometric detection.

PMID- 29594555
TI  - Enantiomeric separation of adrenaline, noradrenaline, and isoprenaline by
      capillary electrophoresis using streptomycin-modified gold nanoparticles.
AB  - Enantiomeric separations of the adrenergic compounds adrenaline, noradrenaline,
      and isoprenaline were studied. Electromigrative separations were performed in
      uncoated fused silica capillaries using streptomycin-modified gold nanoparticles
      (ST-AuNPs) as an additive to the background electrolyte. The ST-AuNPs are shown
      to serve as an effective chiral selector. The modified AuNPs were characterized
      in terms of size and zeta potential, and by IR and UV-vis spectra. The effects of
      ST-AuNP concentration, pH value, temperature, and separation voltage on the
      separations were systematically studied. Under optimized experimental conditions,
      racemic mixtures of the respective adrenergic drugs were baseline-separated
      within 7 min with a resolution of up to 7.5. The relative standard deviations of
      the resolution in inter-day and intra-day studies (n = 5) were generally <5%.
      Graphical abstract Schematic of the method for enantiomeric separations. (A): At
      low concentrations of streptavidinylated gold nanoparticles (ST-AuNPs), the
      better matching enantiomer is preferably "transported" by the ST-AuNPs; (B) ST
      AuNP concentration increased to an optimal value; (C): The ST-AuNP concentration
      is too high; even poorly matching enantiomers will be transported simultaneously.

PMID- 29594556
TI  - A stir foam composed of graphene oxide, poly(ethylene glycol) and natural latex
      for the extraction of preservatives and antioxidant.
AB  - A stir foam composed of graphene oxide, poly(ethylene glycol) and natural latex
      (GO-PEG-NL) was prepared for use in micro-solid phase extraction sorbent of
      preservative agents and antioxidants from cosmetic products. The extracted
      analytes were quantified by GC-MS. Under the optimized conditions, the
      calibration plots are linear in the concentration ranges between 5.0 MUg.L-1 to
      1.0 mg.L-1 for benzoic acid, of 10.0 MUg.L-1 to 1.0 mg.L-1 for 2-methyl-3
      isothiazolinone (MI), and between 1.0 MUg.L-1 and 1.0 mg.L-1 for both 3-tert
      butyl-4-hydroxyanisole (BHA) and 2,6-di-tert-butyl-p-hydroxytoluene (BHT). The
      LODs are 1.0 MUg.L-1 for benzoic acid, 5.0 MUg.L-1 for MI and 0.5 MUg.L-1 for
      both BHA and BHT. The stir-foam can be easily prepared, is inexpensive and well
      reproducible (RSDs <3%, for n = 6). It can be re-used for up to 12 times after
      which extraction efficiency has dropped to 90%. The method was successfully
      applied to the determination of preservatives and antioxidants in cosmetic
      samples. Recoveries from spiked samples ranged between 94.5 +/- 2.1% and 99.8 +/-
      1.8%. Graphical abstract A stir foam was prepared from graphene oxide,
      poly(ethylene glycol) and natural latex (GO-PEG-NL) and is shown to be a most
      viable sorbent for the microextraction of trace amounts of preservative agents
      and antioxidants from cosmetic products.

PMID- 29594557
TI  - Aptamer based voltammetric determination of ampicillin using a single-stranded
      DNA binding protein and DNA functionalized gold nanoparticles.
AB  - An aptamer based method is described for the electrochemical determination of
      ampicillin. It is based on the use of DNA aptamer, DNA functionalized gold
      nanoparticles (DNA-AuNPs), and single-stranded DNA binding protein (ssDNA-BP).
      When the aptamer hybridizes with the target DNA on the AuNPs, the ssDNA-BP is
      captured on the electrode surface via its specific interaction with ss-DNA. This
      results in a decreased electrochemical signal of the redox probe Fe(CN)63- which
      is measured best at a voltage of 0.188 mV (vs. reference electrode). In the
      presence of ampicillin, the formation of aptamer-ampicillin conjugate blocks the
      further immobilization of DNA-AuNPs and ssDNA-BP, and this leads to an increased
      response. The method has a linear reposne that convers the 1 pM to 5 nM
      ampicillin concentration range, with a 0.38 pM detection limit (at an S/N ratio
      of 3). The assay is selective, stable and reproducible. It was applied to the
      determination of ampicillin in spiked milk samples where it gave recoveries
      ranging from 95.5 to 105.5%. Graphical abstract Schematic of a simple and
      sensitive electrochemical apta-biosensor for ampicillin detection. It is based on
      the use of gold nanoparticles (AuNPs), DNA aptamer, DNA functionalized AuNPs (DNA
      AuNPs), and single-strand DNA binding protein (SSBP).

PMID- 29594558
TI  - Antimicrobial peptides produced by Brevibacillus spp.: structure, classification
      and bioactivity: a mini review.
AB  - Species that are currently listed under the genus Brevibacillus (formerly,
      Bacillus brevis cluster) have been a rich source of antimicrobial peptides for
      many decades. The first known peptide antibiotic, gramicidin, is presumed to be
      produced by a Brevibacillus sp. Members of the genus are widely spread in nature.
      They can be found in a variety of environments including intestinal tracts of
      animals, seawater, and soil. Some Brevibacillus strains have been used
      commercially as probiotics. Bioactive peptides produced by Brevibacillus spp.
      include antibacterial, antifungal and anti-invertebrate agents. Brevibacillus
      antimicrobial peptides are synthesized through ribosomal or nonribosomal pathway;
      these two groups can be further categorized based on specific structural features
      such as cyclization and presence of lipid chain. Some of the antimicrobial
      compounds produced by this genus share structural similarities that were
      overlooked previously. For example, the structural similarity between BT peptide,
      brevibacillin, and bogorol was revealed only recently. Here we review and
      classify Brevibacillus antimicrobial peptides and summarize their bioactivities
      and potential applications.

PMID- 29594559
TI  - A lateral flow immunoassay for straightforward determination of fumonisin
      mycotoxins based on the quenching of the fluorescence of CdSe/ZnS quantum dots by
      gold and silver nanoparticles.
AB  - A lateral flow immunoassay (LFIA) was developed for the determination of
      fumonisin mycotoxins. The fluorescence of CdSe/ZnS quantum dots (QDs), observed
      at excitation/emission wavelengths of 365/525 nm, is suppressed by the addition
      of silver nanoparticles (SNPs) or gold nanoparticles (GNPs) because SNPs overlap
      the excitation bands of the QDs, and GNPs overlap the emission bands. The
      fluorescence of the QDs is recovered upon addition of fumonisins, allowing for
      the sensitive detection in "positive mode" of the target mycotoxin by monitoring
      the changes of the QDs fluorescence intensity. The SNPs are found to be the most
      effective quenchers, while the use of GNPs allows for an efficient recovery of
      fluorescence and can be employed in the LFIA. The method was successfully applied
      to the fluorometric determination of fumonisins in spiked maize flour samples.
      The visual detection limit is at the ng.mL-1 level. This is four times lower
      compared to the colorimetric LFIA based on the use of the conventional gold NPs.
      Graphical abstract Schematic of the fluorescence quenching lateral flow
      immunoassay that uses fluorescent quantum dots (QD) and metal nanoparticles (NP)
      as the quencher: the binding of NP-labelled antibody to the antigen (purple
      triangle) modulates QD luminescence at the Test line, allowing for 'positive
      mode' detection of fumonisins. The NP accumulation at Control line assures
      validity of the test.

PMID- 29594561
TI  - Microfluidic paper-based device for colorimetric determination of glucose based
      on a metal-organic framework acting as peroxidase mimetic.
AB  - This work presents a microfluidic paper-based analytical device (MUPAD) for
      glucose determination using a supported metal-organic framework (MOF) acting as a
      peroxidase mimic. The catalytic action of glucose oxidase (GOx) on glucose causes
      the formation of H2O2, and the MOF causes the oxidation of 3,3',5,5'
      tetramethylbenzidine (TMB) by H2O2 to form a blue-green product with an
      absorption peak at 650 nm in the detection zone. A digital camera and the iOS
      feature of a smartphone are used for the quantitation of glucose with the S
      coordinate of the HSV color space as the analytical parameter. Different factors
      such as the concentration of TMB, GOx and MOF, pH and buffer, sample volume,
      reaction time and reagent position in the MUPAD were optimized. Under optimal
      conditions, the value for the S coordinate increases linearly up to 150 MUmol.L-1
      glucose concentrations, with a 2.5 MUmol.L-1 detection limit. The MUPAD remains
      stable for 21 days under conventional storage conditions. Such an enzyme mimetic
      based assay to glucose determination using Fe-MIL-101 MOF implemented in a
      microfluidic paper-based device possesses advantages over enzyme-based assays in
      terms of costs, durability and stability compared to other existing glucose
      determination methods. The procedure was applied to the determination of glucose
      in (spiked) serum and urine. Graphical abstract Schematic representation of
      microfluidic paper-based analytical device using metal-organic framework as a
      peroxidase mimic for colorimetric glucose detection with digital camera or
      smartphone and iOS app readout.

PMID- 29594560
TI  - Rate-limiting steps in the Saccharomyces cerevisiae ergosterol pathway: towards
      improved ergosta-5,7-dien-3beta-ol accumulation by metabolic engineering.
AB  - Ergosterol is the predominant nature sterol constituent of plasma membrane in
      Saccharomyces cerevisiae. Herein, the biosynthetic pathway of ergosterol was
      proposed to be metabolically engineered for the efficient production of ergosta
      5,7-dien-3beta-ol, which is the precursor of vitamin D4. By target disruption of
      erg5, involved in the end-steps of post-squalene formation, predominantly
      accumulated ergosta-5,7-dien-3beta-ol (4.12 mg/g dry cell weight). Moreover, the
      rate-limiting enzymes of ergosta-5,7-dien-3beta-ol biosynthesis were
      characterized. Overexpression of Hmg1p led to a significant accumulation of
      squalene, and induction of Erg1p/Erg11p expression raised the yield of both total
      sterols and ergosta-5,7-dien-3beta-ol with no obvious changes in growth behavior.
      Furthermore, the transcription factor allele upc2-1 was overexpressed to explore
      the effect of combined induction of rate-limiting enzymes. Compared with an
      obviously enhanced yield of ergosterol in the wild-type strain, decreases of both
      the ergosta-5,7-dienol levels and the total sterol yield were found in Deltaerg5
      upc2-1, probably due to the unbalanced NADH/NAD+ ratio observed in the erg5
      knockouts, suggesting the whole-cell redox homeostasis was also vital for end
      product biosynthesis. The data obtained in this study can be used as reference
      values for the production of sterol-related intermediates involved in the post
      squalene biosynthetic pathway in food-grade S. cerevisiae strains.

PMID- 29594562
TI  - Voltammetric lidocaine sensor by using a glassy carbon electrode modified with
      porous carbon prepared from a MOF, and with a molecularly imprinted polymer.
AB  - The work describes a hybrid electrochemical sensor for highly sensitive detection
      of the anesthetic lidocaine (LID). Porous carbon (PC) was synthesized from an
      isoreticular metal-organic framework-8 (IRMOF-8) and drop cast onto a glassy
      carbon electrode (GCE). A layer of a molecularly imprinted polymer (MIP) layer
      was then fabricated in situ on the modified GCE by electro-polymerization, with
      LID acting as the template and resorcinol as the functional monomer.
      Hexacyanoferrate is used as an electrochemical probe. The electrical signal
      (typically acquired at 0.335 V vs. SCE) increases linearly in the 0.2 pM to 8 nM
      LID concentration range, with a remarkable 67 fM detection limit (at an S/N ratio
      of 3). The sensor is stable and selective. Eventually, rapid and accurate
      detection of LID in spiked real samples was successfully realized. Graphical
      abstract ?.

PMID- 29594563
TI  - Immobilization of horseradish peroxidase on amino-functionalized carbon dots for
      the sensitive detection of hydrogen peroxide.
AB  - The authors describe the preparation of amino-functionalized carbon dots (NH2
      CDs) via a one-step hydrothermal process using silver nitrate and chitosan as the
      precursors. The NH2-CDs have a fairly consistent size distribution with an
      average size of 2.8 +/- 0.5 nm. This is attributed to the introduction of Ag(I)
      both as a catalyst and a precipitant. The NH2-CDs are highly crystalline. Their
      surface carries amino groups and carboxy groups which is confirmed by
      transmission electron microscopy (TEM) and Fourier transform infrared (FTIR)
      spectroscopy. Horseradish peroxidase (HRP) was immobilized in the NH2-CDs and
      then placed on a glassy carbon electrode (GCE). Spectroscopic and electrochemical
      analyses evidenced the stability and good bioactivity of the immobilized HRP.
      This reveals that NH2-CD is a desirable matrix for enzyme immobilization. The
      modified GCE exhibits enhanced electro-catalytic activity towards hydrogen
      peroxide (H2O2) reduction as compared to that of plain CDs. The effects of pH
      value and loading on the performances of the modified GCEs were studied. Under
      optimized conditions, the biosensor has a linear response in the 5 to 590 nM H2O2
      concentration range, with a 1.8 nM defection limit (at an S/N ratio of 3). The
      sensor is stable, reproducible and selective. Finally, the sensor was applied to
      determine H2O2 in real samples, and satisfactory recoveries were achieved.
      Graphical abstract Amino-functionalized carbon dots (NH2-CDs) can provide more
      active sites and a friendly microenvironment for horseradish peroxidase (HRP)
      immobilization. Thus, a novel sensitive H2O2 biosensor has been developed.

PMID- 29594564
TI  - Photoelectrochemical immunoassay for human interleukin 6 based on the use of
      perovskite-type LaFeO3 nanoparticles on fluorine-doped tin oxide glass.
AB  - A film of perovskite-type LaFeO3 nanoparticles (NPs) was deposited on fluorine
      doped tin oxide (FTO) conducting glass via dipping-lifting and calcination.
      Scanning electron microscopy shows that the NPs are evenly distributed on the
      surface of the glass. The modified glass was further coated with antibody against
      human interleukin 6 (IL-6) to result in a photoelectrochemical immunosensor for
      IL-6. The well-established photoelectrochemical immunoassay has a linear current
      response in the range of 0.1 pg.mL-1 to 0.1 MUg.mL-1 and a detection limit as low
      as 33 fg.mL-1. Graphical abstract Schematic of a novel photoelectochemical
      immunoassay for the measurement of IL-6 based on perovskite-type LaFeO3
      nanoparticles. The immunoassay had a higher sensitivity and may also be applied
      to other bioanalysis and environment monitoring.

PMID- 29594565
TI  - Electrochemical quercetin sensor based on a nanocomposite consisting of
      magnetized reduced graphene oxide, silver nanoparticles and a molecularly
      imprinted polymer on a screen-printed electrode.
AB  - An electrochemical quercetin (QR) sensor is described that is based on the use of
      magnetic reduced graphene oxide (MrGO) incorporated into a molecularly imprinted
      polymer (MIP) on the surface of a screen-printed electrode (SPE). The MrGO
      consists of reduced graphene oxide (rGO), magnetite (Fe3O4) and silver
      nanoparticles (Ag). The analyte (QR) is electrostatically adsorbed on the surface
      of the MrGO. Finally, the MIP was deposited via in-situ polymerization. The
      composite was characterized by X-ray diffraction, Fourier transform infrared
      spectroscopy and Vibrating sample magnetometry. The morphologies and
      electrochemical properties of different electrodes were characterized by Field
      emission scanning electron microscopy, Electrochemical impedance spectroscopy and
      differential pulse voltammetry. Under optimal conditions, the modified electrode
      has a linear response in the 20 nM to 250 MUM QR concentration range. The limit
      of detection is 13 nM (at an S/N ratio of 3). The electrode is selective, stable,
      regenerable and reliable. It was applied to the determination of QR in spiked
      pharmaceutical samples and gave satisfactory results. Graphical abstract
      Schematic presentation of a method for sensing quercetin. It is based on the use
      of screen printed electrode modified with magnetized reduced graphene oxide and a
      molecularly imprinted polymer.

PMID- 29594567
TI  - On-site preconcentration of pesticide residues in a drop of seawater by using
      electrokinetic trapping, and their determination by surface-enhanced Raman
      scattering.
AB  - The authors have developed a method for simultaneous quantification of several
      charged pesticides (as shown for amitrole, simazine, trichlorfon and bisultap).
      It is based on the use of a reduced graphene oxide-modified screen-printed
      electrode (RGO-SPE) and combines electrokinetic trapping (EKT) and surface
      enhanced Raman scattering (SERS). When a 50 MUL droplet containing negatively
      charged RGO and positively charged gold nanorods is placed on the SPE, the RGO
      and gold nanorods are selectively attracted on the surface of the SPE during EKT.
      This leads to the formation of sandwich-type hybrid substrates. The resulting
      substrates also contain Raman "hot spots" among the high-density gold nanorods.
      This, along with the excellent adsorption performance of RGO, makes it an
      excellent SERS substrate for on-site detection of the charged pesticides. The
      method is highly reproducible and long-term stable. The spot-to-spot variation of
      the intensity of the SERS is <15%, and the performance of SERS activity is
      maintained over a period of 6 weeks. The method works over a wide range of
      concentrations (0.5 nM to 4 MUM) for charged pesticides under optimal conditions,
      with a sub-nanomolar detection limit (at a signal to noise ratio of 3). The EKT
      SERS method requires only microliter volumes and takes only minutes for
      completion. Therefore, the method provides high sensitivity for detection while
      preserving the selectivity and stability required for reliable quantitative
      analysis. Graphical abstract A method combining electrokinetic trapping and SERS
      can be used for simultaneous detection of charged pesticides in a drop of
      seawater.

PMID- 29594568
TI  - [Laser membranotomy in the management of acute premacular hemorrhage : Case
      report and overview on the approach].
AB  - Acute premacular bleeding is often associated with vasoproliferative retinal
      changes, vascular anomalies or a Valsalva maneuver. The diagnosis is made during
      the funduscopic examination and can if necessary be confirmed with optical
      coherence tomography (OCT). This article presents a case example with a sub-inner
      limiting membrane (ILM)/sub-hyaloidal bleeding. Furthermore, we present various
      treatment options and give an overview on the use of the Nd:YAG laser for laser
      membranotomy as a minimally invasive treatment option with a low complication
      profile.

PMID- 29594566
TI  - Electrochemical nonenzymatic sensing of glucose using advanced nanomaterials.
AB  - An overview (with 376 refs.) is given here on the current state of methods for
      electrochemical sensing of glucose based on the use of advanced nanomaterials. An
      introduction into the field covers aspects of enzyme based sensing versus
      nonenzymatic sensing using nanomaterials. The next chapter cover the most
      commonly used nanomaterials for use in such sensors, with sections on uses of
      noble metals, transition metals, metal oxides, metal hydroxides, and metal
      sulfides, on bimetallic nanoparticles and alloys, and on other composites. A
      further section treats electrodes based on the use of carbon nanomaterials (with
      subsections on carbon nanotubes, on graphene, graphene oxide and carbon dots, and
      on other carbonaceous nanomaterials. The mechanisms for electro-catalysis are
      also discussed, and several Tables are given where the performance of sensors is
      being compared. Finally, the review addresses merits and limitations (such as the
      frequent need for working in strongly etching alkaline solutions and the need for
      diluting samples because sensors often have analytical ranges that are far below
      the glucose levels found in blood). We also address market/technology gaps in
      comparison to commercially available enzymatic sensors. Graphical Abstract
      Schematic representation of electrochemical nonenzymatic glucose sensing on the
      nanomaterials modified electrodes. At an applied potential, the nanomaterial
      modified electrodes exhibit excellent electrocatalytic activity for direct
      oxidation of glucose oxidation.

PMID- 29594569
TI  - Boronate-modified hollow molecularly imprinted polymers for selective enrichment
      of glycosides.
AB  - D-Glucose was used as a dummy template in a strategy to fabricate boronate-based
      hollow molecularly imprinted polymers (h-MIPs) for the recognition of glycosides.
      3-Aminophenylboronic acid (APBA) was selected as the functional monomer to impart
      glycoside binding capability. A polystyrene core was synthesized via an
      emulsifier-free emulsion polymerization. It was then be corroded to form a hollow
      structure where the binding sites on the inner surface can be fully utilized.
      Adsorption studies indicate that the resulting h-MIPs can specifically recognize
      glycosides. The h-MIPs were applied as a sorbent for solid phase extraction of
      the glycosides (daidzin, glycitin, rutin, and genistin) in soy products.
      Following desorption with 1% TFA in acetonitrile-water (3:7, v/v), the glycosides
      were quantified by HPLC with UV detection. The detection limits for the
      glycosides range from 3.5 to 10.8 ng.mL-1. Graphical abstract Boronate-affinity
      hollow molecularly imprinted polymers using D-glucose as dummy template were
      prepared as solid phase extraction adsorbents for selective enrichment of
      glycosides in soy products prior to quantitation by HPLC-UV.

PMID- 29594570
TI  - A colorimetric gold nanoparticle aggregation assay for malathion based on target
      induced hairpin structure assembly of complementary strands of aptamer.
AB  - The authors describe a method for the colorimetric determination of the pesticide
      malathion. It is based on the use of a hairpin structure consisting of a
      complementary strand of aptamer and a double-stranded DNA (dsDNA) structure to
      protect gold nanoparticles (AuNPs) against salt-induced aggregation. In the
      absence of malathion, the dsDNA structure is preserved on the surface of AuNPs
      and the color of the AuNPs in solutions containing NaCl remains red. However, in
      the presence of malathion, a hairpin structure of complementary strand is formed.
      The Aptamer/Malathion complex and the complementary strand are released from the
      surface of the AuNPs. As a result, the AuNPs undergo salt-induced aggregation
      which is accompanied by a color change to blue. The assay allows malathion to be
      quantified within 35 min (A650/A520 was measured). The detection limit is 1 pM,
      and response is linear in the 5 pM to 10 nM malathion concentration range. The
      method is specific and was successfully applied to the determination of malathion
      in spiked human serum samples. Graphical abstract Schematic representation of
      detection of malathion based on dsDNA-modified gold nanoparticles (AuNPs) and the
      hairpin structure of the complementary strand.

PMID- 29594572
TI  - ?

PMID- 29594571
TI  - Branched silver nanowires on fluorine-doped tin oxide glass for simultaneous
      amperometric detection of H2O2 and of 4-aminothiophenol by SERS.
AB  - This study introduces a two-step method for the deposition of branched silver
      nanowires (AgNWs) on fluorine-doped tin oxide (FTO) glass. This material serves
      as both an active surface-enhanced Raman-scattering (SERS) substrate and as an
      enzyme-free electrochemical sensor for H2O2. This dual functionality is
      systematically studied. The AgNWs as the main trunk were first deposited on FTO
      by spray-coating. Silver branches were then electrochemically produced on the
      preformed NWs. Scanning electron microscopy, X-ray diffraction and X-ray
      photoelectron spectrometry were employed to characterize morphology, composition
      and microstructure. SERS experiments show that the branched AgNW/FTO substrate
      exhibits excellent performance in detecting 4-aminothiophenol at an ultra-low
      concentration of 0.1 fM. Simultaneously, this material displays an excellent
      electrocatalytic response to H2O2 reduction at a concentration as low as 1 MUM.
      The sensor has a rapid response and two linear analytical ranges that extend from
      0.25 to 300 MUM, and from 0.3 to 2.6 mM of H2O2, respectively. The ultrahigh
      sensitivity and satisfactory reproducibility highlights the merit of this
      hierarchical AgNW dendritic structure for sensing applications. Graphical
      abstract Branched silver nanowires can serve as both an active surface-enhanced
      Raman scattering substrate and as an electrochemical sensor for H2O2. This dual
      functionality is systematically investigated.

PMID- 29594573
TI  - Reduced graphene oxide functionalized with a CoS2/ionic liquid composite and
      decorated with gold nanoparticles for voltammetric sensing of dopamine.
AB  - A nanohybrid electrode was prepared by functionalizing reduced graphene oxide
      nanosheets (GNs) with gold nanoparticles (AuNP), CoS2, and an ionic liquid. It is
      shown to enable voltammetric determination of dopamine (DA). The AuNPs were
      electrodeposited onto the electrode that was first modified with CoS2 and the IL
      GNs to obtain a well-defined 3-dimensional and porous structure. The nanohybrid
      material displays high catalytic activity and an ultrasensitive cyclic
      voltammetric response to DA. The peak current (best measured at a working voltage
      of 0.17 V vs. Ag/AgCl) increases linearly in the 0.1 to 400 MUM DA concentration
      range, with a 40 nM detection limit (at S/N = 3). The electrode was successfully
      applied to the determination of DA in spiked serum samples. Graphical abstract
      Schematic of the preparation of a nanohybrid electrode odified with graphene
      oxide nanosheets functionalized with gold nanoparticles/CoS2/ionic liquid by
      electrodeposition. The electrode exhibits excellent electrocatalytic performance
      with respect to the electrochemical detection of dopamine. The determination of
      the DPV curves provides satisfactory results which can be characterized by a
      linear response for DA concentrations ranging from 0.1 to 400.0 MUM with a 40 nM
      detection limit (at S/N = 3).

PMID- 29594574
TI  - Aptamer-based fluorescent platform for ultrasensitive adenosine detection
      utilizing Fe3O4 magnetic nanoparticles and silver nanoparticles.
AB  - The authors describe an aptamer-based fluorescent assay for adenosine (Ade). It
      is based on the interaction between silver nanoparticles (AgNPs) and CdTe quantum
      dots (QDs). The beacon comprises a pair of aptamers, one conjugated to Fe3O4
      magnetic nanoparticles, the other to AgNPs. In the presence of Ade, structural
      folding and sandwich association of the two attachments takes place. After
      magnetic separation, the associated sandwich structures are exposed to the QDs.
      The AgNPs in sandwich structures act as the signaling label of Ade by quenching
      the fluorescence of QDs (at excitation/emission wavelengths of 370/565 nm) via
      inner filter effect, electron transfer and trapping processes. As a result, the
      fluorescence of QDs drops with increasing Ade concentration. The assay has a
      linear response in the 0.1 nM to 30 nM Ade concentration range and a 60 pM limit
      of detection. The assay only takes 40 min which is the shortest among the aptamer
      based methods ever reported. The method was successfully applied to the detection
      of Ade in spiked biological samples and satisfactory recoveries were obtained.
      Graphical abstract Schematic of a highly efficient and convenient adenosine (Ade)
      fluorometric assay. It is based on the interaction between Ag nanoparticles (NPs)
      and CdTe quantum dots (QDs). Ade aptamers (ABA1 and ABA2) are used as recognition
      unit and Fe3O4 magnetic nanoparticles act as magnetic separator. The assay
      exhibits superior sensitivity and speediness.

PMID- 29594575
TI  - A novel SERS nanoprobe based on the use of core-shell nanoparticles with embedded
      reporter molecule to detect E. coli O157:H7 with high sensitivity.
AB  - The authors report on a surface-enhanced Raman scattering (SERS) nanoprobe for
      the specific detection of Escherichia coli O157:H7 (E. coli O157:H7). Gold
      nanoparticles (AuNPs) were coated with a thick silica shell, and the Raman
      reporter (4,4'-dipyridyl) was embedded between gold nanoparticle and silica
      shell. This technique prevents any external effects on the AuNPs from the
      environment and avoids any interaction between the Raman reporter and possible
      impurities. Compared to the SERS nanoprobe of the conventional AuNP/AgNP type,
      the present nanoprobe can be applied in complex biochemical circumstances without
      aggregation because of its excellent stability. The SERS nanoprobeis stable for
      up to 50 h. The probe was applied to the SERS detection of E. coli O157:H7 by
      exploiting the Raman band peaking at 1612 cm-1 of 4,4'-dipyridyl (DP). The limit
      of detection is as low as 10 CFU.mL-1. The technique was successfully employed to
      the detection of E. coli O157:H7 in real samples, achieving recoveries between
      95.5 and 114.8%. Graphical abstract A novel surface-enhanced Raman scattering
      (SERS) nanoprobe based on the silica encapsulated gold nanoparticles (SEGNs)
      combining with the functionalized magnetic nanoparticles (MNPs), detecting E.
      coli O157:H7 with high sensitivity and specificity.

PMID- 29594577
TI  - Detection of nucleic acids and elimination of carryover contamination by using
      loop-mediated isothermal amplification and antarctic thermal sensitive uracil-DNA
      glycosylase in a lateral flow biosensor: application to the detection of
      Streptococcus pneumoniae.
AB  - The authors report on a loop-mediated isothermal amplification (LAMP) scheme that
      uses antarctic thermally sensitive uracil-DNA-glycosylase (AUDG) for simultaneous
      detection of nucleic acids and elimination of carryover contamination. It was
      applied in a lateral flow assay (LFA) format. The assay has attractive features
      in that it does not require the use of labeled primers or probes, and can
      eliminate false-positive results generated by unwanted hybridization between two
      labeled primers or between a labeled primer and probe. LAMP amplification and
      AUDG digestion are conducted in a single pot, and the application of a closed
      tube reaction prevents false-positives due to carryover contamination. The method
      was applied to the detection of the human pathogen Streptococcus pneumoniaein in
      pure cultures and spiked blood samples. This LFA can detect S. pneumoniae in pure
      cultures with a 25 fg.MUL-1 detection limit and in spiked blood samples with a
      470 cfu.mL-1 detection limit. Conceivably, this assay can be applied to the
      detection of various other targets if the specific LAMP primers are available.
      Graphical abstract ?.

PMID- 29594576
TI  - Endophytic bacterial microbiome associated with leaves of genetically modified
      (AtAREB1) and conventional (BR 16) soybean plants.
AB  - Plant leaves (phyllosphere) have a great potential for colonization and microbial
      growth, consisting of a dynamic environment in which several factors can
      interfere with the microbial population structure. The use of genetically
      modified (GM) plants has introduced several traits in agriculture, such as the
      improvement of plant drought tolerance, as observed in the AtAREB1 transcription
      factor overexpression in soybean (Glycine max L. Merrill). The present study
      aimed at investigating the taxonomic and functional profile of the leaf microbial
      community of bacteria found in GM (drought-tolerant event 1Ea2939) and
      conventional (BR 16) soybean plants. Bacterial DNA was extracted from leaf
      samples collected from each genotype and used for microbial diversity and
      richness analysis through the MiSeq Illumina platform. Functional prediction was
      performed using the PICRUSt tool and the STAMP v 2.1.3 software. The obtainment
      of the GM event 1Ea2939 showed minimum effects on the microbial community and in
      the potential for chemical-genetic communication, i.e. in the potential for
      symbiotic and/or mutualistic interaction between plants and their natural
      microbiota.

PMID- 29594578
TI  - Colorimetric aggregation based cadmium(II) assay by using triangular silver
      nanoplates functionalized with 1-amino-2-naphthol-4-sulfonate.
AB  - A colorimetric method is described for sensitive and low-cost detection of
      Cd(II). It is based on the use of triangular silver nanoplates (tri-AgNPs)
      modified with 1-amino-2-naphthol-4-sulfonate (ANS) acting as a colorimetric
      probe. ANS is first linked to the tri-AgNPs via electrostatic interaction of the
      sulfo groups. In the absence of analyte, ANS on the surface of tri-AgNPs protects
      them from aggregation. In the presence of Cd(II), the tri-AgNPs aggregate due to
      the interaction between ANS and Cd(II). This results in a distinct color change
      from blue (absorption peak at 710 nm) to green (peak at 770 nm). UV-vis
      spectrometry and image analyses demonstrate that this method exhibits selective
      and sensitive colorimetric response to Cd(II). The color change can be easily
      detected with bare eyes. Response is linear in the 30 to 70 MUM concentration
      range, and the detection limit is 30 nM. Graphical abstract A colorimetric method
      for sensitive, and low-cost detection of Cd(II) based on the use of tri-AgNPs
      modified with ANS acting as a colorimetric probe was presented.

PMID- 29594579
TI  - The CoOOH-TMB oxidative system for use in colorimetric and test strip based
      determination of ascorbic acid.
AB  - The authors report that cobalt oxyhydroxide (CoOOH) nanoflakes possess intrinsic
      oxidizing ability to directly oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to
      form a blue colored product (oxTMB) even in the absence of H2O2 and oxygen. In
      the presence of ascorbic acid (AA), less of the blue product is formed because AA
      reduces oxTMB. These findings constitute a new scheme for colorimetric detection
      of AA. Absorbance, best measured at 652 nm, linearly drops in the 10 nM to 1 MUM
      AA concentration range, and the limit of detection is 5 nM (at an S/N ratio of
      3). The reaction is complete within <5 s and highly selective. A strip test has
      been designed for fast and on-spot visual detection of AA. The method was applied
      to the direct estimation of AA in the microdialysate of brain, and also in soft
      drink samples. The strip test is considered to be a promising tool for the rapid
      screening of AA in brain and commercial samples. Graphic abstract Schematic of
      the CoOOH-TMB colorimetric system that exhibits a high selectivity for ascorbic
      acid (AA). A strip test has been designed for fast and on-spot visual detection
      of AA.

PMID- 29594581
TI  - A nanocomposite prepared from a zinc-based metal-organic framework and
      polyethersulfone as a novel coating for the headspace solid-phase microextraction
      of organophosphorous pesticides.
AB  - The authors describe a zinc-based metal-organic framework/polyethersulfone
      nanocomposite (TMU-4/PES) coating deposited on a stainless steel wire via a
      single-phase inversion method. The nanocomposite represents a novel fiber coating
      for headspace solid-phase microextraction of organophosphorous pesticides (OPPs)
      from environmental water and soil samples. The synergistic effects of the high
      surface area and unique porous structure of TMU-4 as well as the rich pi electron
      stacking and mechanical attributes of the PES polymer result in a high affinity
      of the composite for OPPs. Following thermal desorption, the OPPS were quantified
      by gas chromatography with a nitrogen-phosphorus detector. The preparation of the
      coating is simple, and the coated fiber is highly stable and reusable in that it
      can be used in about 100 consecutive extractions/desorption cycles. A central
      composite design was used for assessing the effect of the experimental parameters
      on the extraction process. Under optimized conditions, the limits of detection
      are in the 5-8 ng mL-1 range for the OPPs diazinon, fenitrothion, malathion and
      chlorpyrifos. The average repeatability and fiber-to-fiber reproducibility are
      6.5% and 8.7%, respectively. The method was applied to the trace determination of
      OPPs in (spiked) water and soil samples where it gave good recovery (88-108%) and
      satisfactory reproducibility (5.9-10.1%). Graphical abstract A zinc-based metal
      organic framework/polyethersulfone nanocomposite coating was prepared on a
      stainless steel wire via phase inversion. It was used as a novel fiber coating
      for headspace solid phase microextraction of organophosphorous pesticides from
      water and soil samples.

PMID- 29594580
TI  - Interoception and Its Interaction with Self, Other, and Emotion Processing:
      Implications for the Understanding of Psychosocial Deficits in Borderline
      Personality Disorder.
AB  - PURPOSE OF REVIEW: We review evidence for the potential importance of
      interoception, i.e., the processing of signals arising from inside the body, for
      deficient psychosocial functioning in borderline personality disorder (BPD).
      RECENT FINDINGS: Evidence suggests that variability in interoception interacts
      with higher-order psychological functions such as self, other, and emotion
      processing. These domains are characteristically impaired in BPD, suggesting a
      likely causal role of disturbed interoception in the etiology of the disorder.
      The inability to identify and describe one's own emotional states represents a
      proxy of impaired interoception which might further mediate between the
      perception of inner physiological conditions and psychosocial functioning in BPD.
      There is preliminary evidence explaining how early life stress might adversely
      affect central interoceptive representation and psychosocial functioning in BPD.
      Based on these findings and the specific pattern of disturbances in BPD, we
      propose the crucial role of interoception in an integrated biobehavioral model
      for BPD.

PMID- 29594582
TI  - N-Doped graphene quantum dot@mesoporous silica nanoparticles modified with
      hyaluronic acid for fluorescent imaging of tumor cells and drug delivery.
AB  - The authors describe new bifunctional mesoporous silica nanoparticles (NPs) for
      specific targeting of tumor cells and for intracellular delivery of the cancer
      drug doxorubicin (DOX). Mesoporous silica nanoparticles (MSNPs) were coated with
      blue fluorescent N-graphene quantum dots, loaded with the drug DOX, and finally
      coated with hyaluronic acid (HA). Cellular uptake of the NPs with an architecture
      of the type HA-DOX-GQD@MSNPs enabled imaging of human cervical carcinoma (HeLa)
      cells via fluorescence microscopy. The cytotoxicity of the nanoparticles on HeLa
      cells was also assessed. The results suggest that the NPs are higher cytotoxicity
      effect and exert in living cell imaging ability. Compared to the majority of
      other drug nanocarrier systems, the one described here enables simultaneous DOX
      release and fluorescent monitoring. Graphical abstract Schematic of the
      bifunctional mesoporous silica nanoparticles were obtained via the Stober method,
      along with the doxorubicin loaded and the hyaluronic acid capped. The sensor
      shows good specificity and significant cytotoxicity effect on Hela cells. (TEOS:
      tetraethyl orthosilicate; GQDs: graphene quantum dots; DOX: doxorubicin; HA:
      Hyaluronic acid).

PMID- 29594583
TI  - Impedimetric detection of bacteria by using a microfluidic chip and silver
      nanoparticle based signal enhancement.
AB  - The authors describe a method that can significantly improve the performance of
      impedimetric detection of bacteria. A multifunctional microfluidic chip was
      designed consisting of interdigitated microelectrodes and a micro-mixing zone
      with a Tesla structure. This maximizes the coating of bacterial surfaces with
      nanoparticles and results in improved impedimetric detection. The method was
      applied to the detection of Escherichia coli O157:H7 (E. coli). Silver
      enhancement was accomplished by coating E.coli with the cationic polymer
      diallyldimethylammonium chloride (PDDA) to form positively charged E. coli/PDDA
      complexes. Then, gold nanoparticles (AuNPs) were added, and the resulting E.
      coli/PDDA/AuNPs complexes were collected at interdigitated electrodes via
      positive dielectrophoresis (pDEP). A silver adduct was then formed on the E.
      coli/PDDA/AuNP complexes by using silver enhancement solutions and by using the
      AuNPs as catalysts. The combination of pDEP based capture and of using silver
      adducts reduces impedance by increasing the conductivity of the solution and the
      double layer capacitance around the microelectrodes. Impedance decreases linearly
      in the 2 * 103-2 * 105 cfu.mL-1 E. coli concentration range, with a 500 cfu.mL-1
      detection limit. Egg shell wash samples and tap water spiked with E. coli were
      successfully used for validation, and this demonstrates the practical application
      of this method. Graphical abstract Schematic representation of the AuNP@Ag
      enhancement method integrated with multifunctional microfluidic chip platform for
      impedimetric quantitation of bacteria. The method significantly improves the
      performance of impedimetric detection of bacteria.

PMID- 29594585
TI  - Photoinduced discharge of electrons stored in a TiO2-MWCNT composite to an
      analyte: application to the fluorometric determination of hydrogen peroxide,
      glucose and aflatoxin B1.
AB  - The authors describe an analytical detection scheme based on the use of
      multiwalled carbon nanotubes (MWCNTs) that accept and store electrons upon
      contact with photo-irradiated TiO2 nanoparticles (TiO2-NPs). The Fermi level
      equilibration with photo-irradiated TiO2-NPs has a storage value of 0.35 mM of
      electrons per 120 mg.L-1 of MWCNTs. The stored electrons can be discharged on
      demand upon addition of electron acceptors to the TiO2-NP/MWCNT composite. These
      findings are applied to detect the quencher hydrogen peroxide. H2O2 also is
      produced on enzymatic action of glucose oxidase on glucose, and this enables
      glucose also to be quantified by using the TiO2-NP/MWCNT fluorescent nanoprobe.
      The wide scope of the method also is demonstrated by an assay for aflatoxin B1
      that is making use of an FAM-labeled aptamer where the FAM fluorophore on the
      aptamer quenches the emission of the nanoprobe. The following analytical linear
      ranges and limits of detection are found: H2O2: 0.1-100 MUM and 15 nM; glucose: 5
      200 MUM and 0.5 MUM; aflatoxin: 0.1-40 ng.mL-1 and 0.02 ng.mL-1. The method was
      applied to the determination of glucose in human serum. Graphical abstract The
      assays demonstrated in (b) and (c) are based on the fluorescence quenching
      ability of MWCNTs-TiO2. In the presence of the target (analyte), the fluorescence
      is restored and the target concentration is determined from the percentage of
      fluorescence recovery.

PMID- 29594584
TI  - Genital marginal failures after intensity-modulated radiation therapy (IMRT) in
      squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT.
AB  - Intensity-modulated radiotherapy (IMRT) is considered the preferred option in
      squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while
      minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but
      the technique is more demanding as deep understanding of target structures is
      required. To evaluate genital marginal failure in a cohort of patients with non
      metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy,
      117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT
      and 3DCRT techniques, respectively. All patients underwent clinical and
      radiological examination during their follow-up. Tumor response was evaluated
      with response evaluation criteria in solid tumors v1.1 guideline on regular
      basis. All patients' data were analyzed, and patients with marginal failure were
      identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients
      in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow
      up was 25 months (range 6-78). Progressive disease was registered in 15.6% of
      patients; infield recurrence, distant recurrence and both infield recurrence and
      distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out
      of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal
      septum and left perineal region. In the 3DCRT group, the median follow-up was
      71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal
      failures, localized at recto-vaginal septum and perigenital structures. The rate
      of marginal failures was comparable in IMRT and 3DCRT groups (chi2 test p =
      0.85). In this series, the use of IMRT for the treatment of SCAC did not increase
      the rate of marginal failures offering improved dose conformity to the target.
      Dose constraints should be applied with caution-particularly in females with
      involvement of the vagina or the vaginal septum.

PMID- 29594586
TI  - A cationic conjugated polymer coupled with exonuclease I: application to the
      fluorometric determination of protein and cell imaging.
AB  - A strategy is described for the detection of protein by using a cationic
      fluorescent conjugated polymer coupled with exonuclease I (Exo I). Taking
      streptavidin (SA) as model protein, it is observed that Exo I can digest single
      stranded DNA conjugated with biotin and carboxyfluorescein (P1) if SA is absent.
      This leads to the formation of small nucleotide fragments and to weak
      fluorescence resonance energy transfer (FRET) from the polymer to P1. If,
      however, SA is present, the high affinity of SA and biotin prevents the digestion
      of P1 by Exo I. This results in the sorption of P1 on the surface of the polymer
      through strong electrostatic interaction. Hence, efficient FRET occurs from the
      fluorescent polymer to the fluorescent label of P1. Fluorescence is measured at
      an excitation wavelength of 370 nm, and emission is measured at two wavelengths
      (530 and 425 nm). The ratio of the two intensities (I530/I425) is directly
      related to the concentration of SA. Under the optimal conditions, the assay has a
      detection limit of 1.3 ng.mL-1. The method was also applied to image the folate
      receptor in HeLa cells, thus demonstrating the versatility of this strategy.
      Graphical abstract A fluorometric strategy is described for protein detection and
      cell imaging based on a cationic conjugated polymer (PFP) coupled with
      exonuclease I (Exo I) trigged fluorescence resonance energy transfer (FRET).

PMID- 29594587
TI  - Dually emitting gold-silver nanoclusters as viable ratiometric fluorescent probes
      for cysteine and arginine.
AB  - Glutathione coated gold and silver nanoclusters (GSH-Au/AgNCs) were synthesized
      by one-pot reduction methods and are found to be viable fluorescent nanoprobes
      for cysteine (Cys) and arginine (Arg), with good selectivity over other amino
      acids. The GSH-Au/AgNCs have two emissions at 616 nm and 412 nm when excited at
      360 nm. With the increased concentration of Cys, the ratio of the emission
      intensities (I616/I412) linearly decreases with Cys in concentration ranging from
      0.05 to 10 MUM and from 10 to 50 MUM, respectively. With increased concentrations
      of Arg, the ratio of I616/I412 linearly decreases with Arg concentration ranging
      from 0 to 50 MUM and from 50 to 100 MUM, respectively. The probe was applied to
      the determination of Cys and Arg in spiked samples of serum and urine where it
      gave good recoveries. Graphical abstract Glutathione-coated gold and silver
      nanoclusters (GSH-Au/AgNCs) were synthesized by one-pot reduction and are found
      to be viable fluorescent nanoprobes for cysteine (Cys) and arginine (Arg).

PMID- 29594588
TI  - Glucose oxidase assisted visual detection of glucose using oxygen deficient alpha
      MoO3-x nanoflakes.
AB  - An optical method is described for the quantitation of glucose by using oxygen
      deficient alpha-MoO3-x nanoflakes. It is based on the use of glucose oxidase
      (GOx) which produces hydrogen peroxide on oxidation of glucose. Hydrogen peroxide
      then oxidizes the alpha-MoO3-x nanoflakes, and this results in a visible color
      change from blue to colorless. The color change can be measured photometrically
      at 740 nm. The method has a 68 nM detection limit. Graphical Abstract Mechanism
      of glucose detection using blue colored oxygen deficient 2D alpha-MoO3-x
      nanoflakes. Hydrogen peroxide (H2O2) is formed as a by-product in the conversion
      of glucose to glucono-1,5-lactone by glucose oxidase (GOx). In the presence of
      H2O2, the oxygen vacancies in alpha-MoO3-x nanoflakes are filled up, and this
      leads to the loss of blue color of the nanoflakes because they are converted back
      to colorless bulk alpha-MoO3.

PMID- 29594589
TI  - Ce doped ZnO/f-MWCNT moss ball like nanocomposite: a strategy for high responsive
      current detection of L-tryptophan.
AB  - An electrochemical sensor is described for the determination of L-tryptophan
      (TRP). The method is based on the use of a glassy carbon electrode (GCE) modified
      with a nanocomposite consisting of moss ball-like cerium-doped ZnO and
      functionalized multiwalled carbon nanotubes (Ce-ZnO/f-MWCNT). Ce-doped ZnO was
      synthesized by a low temperature hydrothermal method. The Ce-ZnO/f-MWCNT
      nanocomposite was characterized by X-ray diffraction, Raman spectroscopy, X-ray
      photoelectron spectroscopy, FTIR and field emission scanning electron microscopy.
      The nanocomposite was drop cast on a GCE for use in electrochemical detection of
      TRP via cyclic voltammetry and differential pulse voltammetry. The oxidation peak
      current (0.76 V vs. Ag/AgCl) is strongly improved compared to a bare GCE. The
      experimental parameters such as solution pH value, scan rate, stability,
      concentration, reproducibility and repeatability were optimized. Response is
      linear in the 10 to 100 nM TRP concentration range, the limit of detection is 1.2
      nM, and the sensitivity is 2.59 MUA.nM-1.cm-2. The electrode was applied to the
      determination of TRP in spiked real samples and gave satisfactory results.
      Graphical abstract Schematic presentation of the preparation of a moss ball like
      nanocomposite consisting of cerium-doped ZnO and functionalized MWCNTs. cerium
      Deposited on a on glassy carbon electrode, it enables nanomolar detection of L
      tryptophan by differential pulse voltammetry.

PMID- 29594590
TI  - Aptamer based vanillin sensor using an ion-sensitive field-effect transistor.
AB  - An aptamer for vanillin was obtained and then used for the development of an
      aptasensor based on an ion-sensitive field-effect transistor (ISFET). This
      aptamer (a single-stranded DNA;ssDNA) was selected using the Capture-SELEX
      protocol, which suites well for selection of aptamers to small molecules. Among
      six aptamer candidates, the aptamer Van_74 with the highest affinity for vanillin
      was chosen (elution of 35% of the aptamer from a solid support in the presence of
      2 mM of vanillin). Van_74 was characterized using nondenaturating PAGE of
      washouts from magnetic beads. It is shown that Van_74 binds to vanillin with an
      dissociation constant of >7.8 MUM (determined by nondenaturating PAGE) and it was
      specific to vanillin in comparison with interferents: benzaldehyde, guaiacol,
      furaneol, ethyl guaiacol and ethyl vanillin. Also it was shown that change of
      buffer composition greatly affected the binding ability of Van_74. For biosensor
      fabrication aptamer was immobilised on the Ta2O5-sensitive surface of the ISFET
      via "click-chemistry". Detection scheme implied dehybridisation of the ssDNA
      probe from the aptamer and release in the solution during the addition of
      vanillin. As a result, the surface potential increase upon vanillin binding with
      the aptamer was detected by the transistor. The biosensor had a detection limit
      of 1.55 * 10-7 M and a dynamic range from 1.55 * 10-7 M to 1 * 10-6 M. Effective
      constant Kd,eff for vanillin binding on biosensor surface was calculated to be (9
      +/- 3) * 10-7 M. This allows selective detection of vanillin in the mixture of
      interferents and in samples of coffee extract. Graphical abstract A biosensor for
      vanillin was developed on the basis of an aptamer that was obtained via Capture
      SELEX and by using an ISFET. This biosensor can be used for vanillin detection in
      presence of interferents and in real sample using an approach of ssDNA probe
      dehybridization.

PMID- 29594591
TI  - S,N-doped carbon dots as a fluorescent probe for bilirubin.
AB  - Carbon dots doped with sulfur and nitrogen (S,N-CDs) were utilised to design a
      paper-stripe based fluorescent probe for the detection of bilirubin. The S,N-CDs
      were synthesized through a microwave assisted route by using citric acid as
      carbon source and L-cysteine as a source of nitrogen and sulfur. The S,N-CDs
      exhibit bright blue fluorescence emission with a peak at 452 nm. Fluorescence is
      quenched by Fe(III) but selectively restored by bilirubin. The quenched
      fluorescent probe exhibit significant selectivity and sensitivity for bilirubin
      in the 0.2 nM to 2 nM concentration range, with a 0.12 nM detection limit. The
      method was applied to the determination of bilirubin in spiked human serum and
      urine samples. The method was used to design a paper based test stripe as a point
      of care device for visual bilirubin detection. Graphical abstract Schematic
      representation of sulphur and nitrogen doped carbon dots whose fluorescence is
      quenched by Fe(III) and turned on by bilirubin. Photograph of the corresponding
      system under day light and UV shows the feasibility of the phenomenon. The
      applicability of the assay was further extended by impregnating the probe on a
      filter paper.

PMID- 29594592
TI  - Selection of DNA aptamers against Mycobacterium tuberculosis Ag85A, and its
      application in a graphene oxide-based fluorometric assay.
AB  - The Mycobacterium Ag85 complex is the major secretory protein of M. tuberculosis.
      It is a potential marker for early diagnosis of tuberculosis (TB). The authors
      have identified specific aptamers for Ag85A (FbpA) via protein SELEX using
      magnetic beads. After twelve rounds of selection, two aptamers (Apt8 and Apt22)
      were chosen from different groups, and their binding constants were determined by
      flow cytometry. Apt22 (labeled with Atto 647N) binds to FbpA with high affinity
      (Kd = 63 nM) and specificity. A rapid, sensitive, and low-cost fluorescent assay
      was designed based on the use of Apt22 and graphene oxide, with a limit of
      detection of 1.5 nM and an analytical range from 5 to 200 nM of FbpA. Graphical
      abstract Schematic illustration of graphene oxide-based aptasensor for
      fluorometric determination of FbpA.

PMID- 29594593
TI  - An electrochemical aptamer-based assay for femtomolar determination of insulin
      using a screen printed electrode modified with mesoporous carbon and 1,3,6,8
      pyrenetetrasulfonate.
AB  - The authors describe an electrochemical method for aptamer-based determination of
      insulin at femtomolar concentrations. The surface of a screen printed electrode
      was modified with ordered mesoporous carbon that was chemically modified with
      1,3,6,8-pyrenetetrasulfonate (TPS). The amino-terminated aptamer was then
      covalently linked to TPS via reactive sulfonyl chloride groups. Subsequently, the
      redox probe Methylene Blue (MB) was interacted into the aptamer. The MB-modified
      binds to insulin and this results in the release of MB and a decreased signal as
      obtained by differential pulse voltammetry, best at a working voltage of -0.3 V
      (versus silver pseudo-reference electrode). Insulin can be quantified by this
      method in the 1.0 fM to 10.0 pM concentration range, with a 0.18 fM limit of
      detection (at 3sigma/slope). The assay was applied to the determination of
      insulin in spiked human serum samples. The method is highly sensitive, selective,
      stable, and has a wide analytical range. Graphical abstract The surface of a
      screen printed electrode was modified with ordered mesoporous carbon-1,3,6,8
      pyrenetetrasulfonate. The amino-terminated aptamer was then linked to the 1,3,6,8
      pyrenetetrasulfonate. Then, the Methylene Blue was interacted into the aptamer.
      The modified electrode was applied to the determination of insulin.

PMID- 29594594
TI  - A lateral flow assay for the determination of human tetanus antibody in whole
      blood by using gold nanoparticle labeled tetanus antigen.
AB  - The authors describe a lateral flow assay (LFA) for the antibody against the
      infectious bacterium Clostridium tetani. Gold nanoparticles (AuNPs) were linked
      to tetanus antigen and are captured in the test line via the formation of a
      sandwich structure composed of AuNP-labeled tetanus antigen, tetanus antibody,
      and tetanus antigen. This leads to the formation of a characteristic red line due
      to the accumulation of AuNPs. The formation of the color line allows for a highly
      sensitive and selective detection of tetanus antibody, both with bare eyes and by
      smartphone-based quantitative analysis. This assay offers a wide detection range
      from 0 to 0.5 IU.mL-1 and has a linear relationship from 0.01 to 0.1 IU.mL-1 with
      an experimental detection limit of 0.01 IU.mL-1. This assay is simple, fast,
      inexpensive and highly selective. When applied to the detection of tetanus
      antibody in spiked whole blood, it provided reliable results that compared well
      to those obtained with a commercial ELISA kit. Graphical abstract ?.

PMID- 29594595
TI  - Vaccine Strategies in Gliomas.
AB  - PURPOSE OF REVIEW: To discuss the current state of glioma vaccine development and
      highlight the challenges associated with clinical implementation of these
      approaches. RECENT FINDINGS: Vaccination strategies against gliomas have matured
      considerably during the past years, although proof-of efficacy from controlled
      clinical trials is still lacking. Advances in antigen discovery, including the
      definition of neoepitopes including epidermal growth factor receptor variant III
      (EGFRvIII), isocitrate dehydrogenase (IDH)1R132H and Histone (H)3.3K27M, using
      multi-omic approaches and computational algorithms allow targeting single
      antigens, but also implementing truly personalized approaches. In addition, new
      concepts of vaccine manufacturing including RNA and DNA vaccines improve
      immunogenicity and applicability in personalized settings. As an increasing
      amount of clinical data defy the concept of the central nervous system (CNS) as a
      strictly immunoprivileged site, novel vaccine approaches enter the clinic
      including critical efforts to identify biomarkers of response and resistance and
      strategies to overcome the immunosuppressive glioma microenvironment.

PMID- 29594596
TI  - Nanosized aptameric cavities imprinted on the surface of magnetic nanoparticles
      for high-throughput protein recognition.
AB  - The authors introduce a new kind of surface artificial biomimetic receptor,
      referred to as aptameric imprinted polymer (AIP), for separation of biological
      macromolecules. Highly dispersed magnetic nanoparticles (MNPs) were coated with
      silica and then functionalized with methacrylate groups via silane chemistry. The
      aptamer was covalently immobilized on the surface of nanoparticles via a "thiol
      ene" click reaction. Once the target analyte (bovine serum albumin; BSA) has
      bound to the aptamer, a polymer is created by 2-dimensional copolymerization of
      short-length poly(ethylene glycol) and (3-aminopropyl)triethoxysilane. Following
      removal of BSA from the polymer, the AIP-MNPs presented here can selectively
      capture BSA with a specific absorbance (kappa) as high as 65. When using this
      AIP, the recovery of BSA from spiked real biological samples is >97%, and the
      adsorption capacity is as high as 146 mg g-1. In our perception, this method has
      a wide scope in that it may be applied to the specific extraction of numerous
      other biomolecules. Graphical abstract Schematic presentation of the AIP (aptamer
      imprinted polymer) introduced here. The surface of silica coated magnetic
      nanoparticles is modified with a polymer that is covalently modified with an
      aptamer against bovine serum albumin (BSA).

PMID- 29594597
TI  - Boletus edulis loaded with gamma-Fe2O3 nanoparticles as a magnetic sorbent for
      preconcentration of Co(II) and Sn(II) prior to their determination by ICP-OES.
AB  - The authors show that the fungus Boletus edulis loaded with gamma-Fe2O3
      nanoparticles is a viable sorbent for magnetic solid phase extraction of trace
      levels of Co(II) and Sn(II). The surface structure of immobilized magnetized B.
      edulis was characterized by FT-IR, SEM and EDX. Experimental parameters were
      optimized. Following elution with 1 M HCl, the ions were quantified by ICP-OES.
      The limits of detection are 21 pg.mL-1 for Co(II), and 19 pg.mL-1 for Sn(II). The
      preconcentration factors are 100 for both ions. The sorption capacities of the
      sorbent are 35.8 mg.g-1 for Co(II) and 29.6 mg.g-1 for Sn(II). The method was
      applied to the analysis of certificated reference materials and gave >=95%
      recoveries with low RSDs. It was also successfully applied to the quantification
      of Co(II) and Sn(II) in spiked environmental and food samples. Graphical abstract
      The fungus Boletus edulis loaded with gamma-Fe2O3 nanoparticles is a viable
      biosorbent for magnetic solid phase extraction (MSPE) of trace levels of Co(II)
      and Sn(II). The surface structure of immobilized magnetized B. edulis was
      characterized by FT-IR, SEM and EDX. Experimental parameters were optimized.

PMID- 29594598
TI  - A hybrid material composed of a polyoxometalate of type BeW12O40 and an ionic
      liquid immobilized onto magnetic nanoparticles as a sorbent for the extraction of
      organophosphorus pesticides prior to their determination by gas chromatography.
AB  - The authors describe a method for the extraction of organophosphorus pesticides
      (OPPs) by using a magnetically separable sorbent consisting of a polyoxometalate
      of type BeW12O40 supported on imidazole functionalized silica-coated cobalt
      ferrite. The sorbent was characterized by X-ray powder diffraction, field
      emission scanning electron micrographs, vibrating sample magnetometry and FT-IR.
      The effects of the amount of adsorbent, pH value, salt concentration, extraction
      time, desorption solvent nature and volume and desorption time were investigated.
      Under optimal conditions, the method resulted in the following figures of merit:
      (a) the linear parts of the calibration plots typically extend from 0.08 to 300
      MUg mL-1 of OPPs; (b) detection limits are between 0.02 to 0.06 ng mL-1; and (c),
      extraction recoveries from spiked samples vary from 70.0 to 89.2%, with relative
      standard deviations between 5.4 and 7.6%. The nanocomposites can be reused up to
      10 times. Compared to other methods for pretreatment and preconcentration of
      OPPs, the new method is more rapid, sensitive, accurate and eco-friendly. The
      method was successfully applied to the determination of the OPP residues in water
      samples and fruit juices. Graphical Abstract Schmatic presenation of the
      synthesis of core-shell magnetic nanoparticles (MNPs) of the type BeW12O40
      ILSCCFNPs, and their application as sorbent for magnetic solid-phase extraction
      (MSPE) of organophosphorus pesticides.

PMID- 29594599
TI  - Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica
      nanoparticles and target induced release of glucose measured with a portable
      glucose meter.
AB  - The authors describe a novel method for the determination of glutathione (GSH).
      Detection is based on target induced release of glucose from MnO2 nanosheet-gated
      aminated mesoporous silica nanoparticles (MSNs). In detail, glucose is loaded
      into the pores of MSNs. Negatively charged MnO2 nanosheets are assembled on the
      MSNs through electrostatic interactions. The nanosheets are reduced by GSH, and
      this results in the release of glucose which is quantified by using a commercial
      electrochemical glucose meter. GSH can be quantified by this method in the 100 nM
      to 10 MUM concentration range, with a 34 nM limit of detection. Graphical
      abstract Glucose is loaded into the pores of mesoporous silica nanoparticles
      (MSNs). MnO2 nanosheets are assembled on MSNs through electrostatic interactions.
      Glutathione (GSH) can reduce the nanosheets, and this results in the release of
      glucose which is quantified by using a commercial glucose meter.

PMID- 29594600
TI  - A ratiometric upconversion nanoprobe for fluorometric turn-on detection of
      sulfite and bisulfite.
AB  - A nanoprobe is described for the ratiometric fluorometric determination of
      sulfite ions. Upconversion nanoparticles (UCNPs) of the type beta
      NaYF4:Yb(III),Er(III),Tm(III) were covalently modified with the molecular probe
      HIAN which is a hydroxynaphthalimide fluorophore modified with a (cationic)
      indolinium moiety. Under excitation at 980 nm, the green emission of the UCNPs
      (peaking at 543 nm) is almost totally quenched, while the NIR emission (peaking
      at 802 nm) remains unaffected. In the presence of sulfite or bisulfite (hydrogen
      sulfite), the green fluorescence is restored and can be visually observed. A
      ratiometric method was worked out by measurement of the ratio of the green and
      NIR emissions. The analytical range extends from 10 to 250 MUM, the limit of
      detection is 0.14 MUM, and the assay can be performed within 40 s. Graphical
      abstract Based on the use of a molecular probe for sulfite and hydrogen sulfite,
      and by exploiting an inner filter effect (IFE), an assay for sulfite/hydrogen
      sulfite was developed by using upconversion nanoparticles (UCNPs). Addition
      reaction of sulfite/bisulfite with the material results in weakened IFE and
      enhanced green fluorescence of the UCNPs at excitation/emission wavelengths of
      980/543 nm.

PMID- 29594601
TI  - Synergic effect of silver nanoparticles and carbon nanotubes on the simultaneous
      voltammetric determination of hydroquinone, catechol, bisphenol A and phenol.
AB  - A glassy carbon electrode (GCE) was modified with multi-walled carbon nanotubes
      (MWCNT) and silver nanoparticles (AgNPs) and applied to the simultaneous
      determination of hydroquinone (HQ), catechol (CC), bisphenol A (BPA) and phenol
      by using square-wave voltammetry. The MWCNTs were deposited on the GCE and the
      AgNPs were then electrodeposited onto the MWCNT/GCE by the application of 10
      potential sweep cycles using an AgNP colloidal suspension. The modified GCE was
      characterized by using SEM, which confirmed the presence of the AgNPs. The
      electrochemical behavior of the material was evaluated by using cyclic
      voltammetry, and by electrochemical impedance spectroscopy that employed
      hexacyanoferrate as an electrochemical probe. The results were compared to the
      performance of the unmodified GCE. The modified electrode has a lower charge
      transfer resistance and yields an increased signal. The peaks for HQ (0.30 V), CC
      (0.40 V), BPA (0.74 V) and phenol (0.83 V; all versus Ag/AgCl) are well separated
      under optimized conditions, which facilitates their simultaneous determination.
      The oxidation current increases linearly with the concentrations of HQ, CC, BPA
      and phenol. Detection limits are in the order of 1 MUM for all 4 species, and the
      sensor is highly stable and reproducible. The electrode was successfully employed
      with the simultaneous determination of HQ, CC, BPA and phenol in spiked tap water
      samples. Graphical abstract A glassy carbon electrode was modified with carbon
      nanotubes and silver nanoparticles and then successfully applied to the
      simultaneous determination of four phenolic compounds. The sensor showed high
      sensitivity in the detection of hydroquinone, catechol, bisphenol A and phenol in
      water samples.

PMID- 29594602
TI  - Preparation of magnetic molecularly imprinted polymers based on a deep eutectic
      solvent as the functional monomer for specific recognition of lysozyme.
AB  - A magnetized molecularly imprinted polymer (MIP) was prepared via a surface
      imprinting technique. An allyl-based deep eutectic solvent was chosen as the
      functional monomer to obtain the polymer for specific recognition of lysozyme. It
      was deposited on silica-coated magnetite nanoparticles. The structure of the
      polymer was confirmed by X-ray diffraction, Fourier transform infrared
      spectrometry, transmission electron microscopy, thermogravimetric analysis and
      vibrating sample magnetometry. The maximum binding capacity of the imprinted
      polymer is found to be 108 mg.g-1, which is higher than that of non-imprinted
      polymer. Compared to reference proteins such as cytochrome C, bovine hemoglobin
      and bovine serum albumin, the MIP shows favorable selectivity for lysozyme.
      Besides, the imprinted polymer can be further used to specifically recognize
      lysozyme from the protein mixture and chicken egg white. Reusability studies
      demonstrate that the polymer can be recycled four times without significant loss
      of adsorption capacity. The LOD of the method is 12.8 MUg.mL-1. The relative
      standard deviations (for n = 3) are 1.38% for precision and 2.76% for
      repeatability. Its facile synthesis, high adsorption performance and excellent
      selectivity to capture lysozyme make this polymer an attractive candidate to be
      applied in biomacromolecular purification. Graphical abstract Magnetic
      molecularly imprinted polymer (MIP) based on deep eutectic solvent as functional
      monomer was fabricated and applied for the specific recognition of lysozyme. The
      MIP exhibits high adsorption capacity and excellent selectivity for lysozyme.

PMID- 29594603
TI  - On site visual detection of Porphyromonas gingivalis related periodontitis by
      using a magnetic-nanobead based assay for gingipains protease biomarkers.
AB  - Porphyromonas gingivalis (P. gingivalis) is a pathogen causing periodontitis. A
      rapid assay is described for the diagnosis of periodontal infections related to
      P. gingivalis. The method is making use of gingipains, a group of P. gingivalis
      specific proteases as a detection biomarker. Magnetic-nanobeads were labeled with
      gingipain-specific peptide substrates and immobilized on a gold biosensing
      platform via gold-thiol linkage. As a result of this, the color of the gold layer
      turns black. Upon cleavage of the immobilized substrates by gingipains, the
      magnetic-nanobeads-peptide fragments were attracted by a magnet so that the
      golden surface color becomes visible again. This assay is highly sensitive and
      specific. It is capable of detecting as little as 49 CFU.mL-1 of P. gingivalis
      within 30 s. Examination of periodontitis patients and healthy control saliva
      samples showed the potential of the assay. The simplicity and rapidity of the
      assay makes it an effective point-of-care device. Graphical abstract Schematic of
      the assay for the detection of P. gingivalis proteases as one of the promising
      biomarkers associated with periodontal diseases.

PMID- 29594604
TI  - A star-shaped polythiophene dendrimer coating for solid-phase microextraction of
      triazole agrochemicals.
AB  - A nanostructured star-shaped polythiophene dendrimer was prepared and used as a
      fiber coating for headspace solid phase microextraction of selected triazolic
      pesticides (tebuconazole, hexaconazole, penconazole, diniconazole,
      difenoconazole, triticonazole) from water samples. The dendrimer with its large
      surface area was characterized by thermogravimetric analysis, UV-Vis spectroscopy
      and field emission scanning electron microscopy. It was placed on a stainless
      steel wire for use in SPME. The experimental conditions for fiber coating,
      extraction, stirring rate, ionic strength, pH value, desorption temperature and
      time were optimized. Following thermal desorption, the pesticides were quantified
      by GC-MS. Under optimum conditions, the repeatability (RSD) for one fiber (for n
      = 3) ranges from 4.3 to 5.6%. The detection limits are between 8 and 12 pg mL-1.
      The method is fast, inexpensive (in terms of equipment), and the fiber has high
      thermal stability. Graphical abstract Schematic presentation of a nanostructured
      star-shaped polythiophene dendrimer for use in headspace solid phase
      microextraction of the triazolic pesticides (tebuconazole, hexaconazole,
      penconazole, diniconazole, difenoconazole, triticonazole). They were then
      quantified by gas chromatography-mass spectrometry.

PMID- 29594606
TI  - Simultaneous determination of captopril and hydrochlorothiazide by using a carbon
      ionic liquid electrode modified with copper hydroxide nanoparticles.
AB  - A carbon electrode modified with the ionic liquid octylpyridinium
      hexafluorophosphate and copper hydroxide nanoparticles was employed in an
      electrochemical assay for simultaneous determination of captopril (CPT) and
      hydrochlorothiazide (HCT). The electrode showed two well-defined oxidation peaks
      for CPT (at 0.22 V) and HCT (at 0.73 V, both vs. Ag/AgCl) at pH 8.0 using square
      wave voltammetry. Calibration plots are linear in the concentration ranges of 0.7
      70 uM (CPT) and 3-600 MUM (HCT), with detection limits of 12 and 60 nM,
      respectively. The electrode was repeatedly applied to simultaneous determination
      of CPT and HCT in pharmaceutical formulation without showing any fouling.
      Graphical abstract Application of carbon ionic liquid electrode (CILE) modified
      with Cu(OH)2 nanoparticles (Cu(OH)2NP/CILE) for the simultaneous determination of
      captopril (CPT) and hydrochlorothiazide (HCT) in pharmaceutical formulation is
      presented.

PMID- 29594605
TI  - Autonomic nervous system and cancer.
AB  - The autonomic nervous system (ANS) is the main homeostatic regulatory system of
      the body. However, this widely distributed neural network can be easily affected
      by cancer and by the adverse events induced by cancer treatments. In this review,
      we have classified the ANS complications of cancer into two categories. The first
      includes direct cancer-related complications, such as primary ANS tumors
      (pheochromocytoma, paraganglioma or neuroblastoma), as well as autonomic
      manifestations induced by non-primary ANS tumors (primary brain tumors and
      metastases). The second comprises indirect ANS complications, which include
      autonomic features related to cancer therapy (chemotherapy, radiotherapy and/or
      surgery) and those not related to cancer therapy, such as paraneoplastic
      autonomic syndromes. We also review the molecular relationship and modulation
      between the ANS and the cancer cells and their microenvironment.

PMID- 29594607
TI  - Graphitic carbon nitride nanosheets as a fluorescent probe for chromium
      speciation.
AB  - A fluorometric method was developed for simultaneous determination of Cr(VI) and
      Cr(III) ions using graphitic carbon nitride nanosheets (g-C3N4 NS) as a nanosized
      fluorescent indicator probe. The g-C3N4 NS were prepared using high-temperature
      carbonization of melamine followed by ultrasonication-assisted liquid
      exfoliation. The g-C3N4 NS display fluorescence with excitation/emission peaks
      located at 320 and 450 nm. The chromium speciation is based on the quenching of g
      C3N4 NS fluorescence. The total concentration of chromium is determined after
      oxidation of Cr(III) to Cr(VI). The Cr(III) content was then calculated by
      subtracting the concentration of Cr(VI) from that of total chromium. The effects
      of pH value, probe amount, and contact time are optimized. Under optimum
      conditions, calibration plots are linear in the range in the 0.01 to 100 MUM
      chromium concentration range. The limit of detection is 3 nM for for Cr(VI). The
      intra- and inter-day relative standard deviations (RSD) of the assay are 3.6-7.5%
      and 4.1-8.5%, respectively. The indicator probe was applied to the determination
      of chromium species in spiked water and food samples, and recoveries were
      satisfactory (93.9-107.0%). Graphical abstract Graphitic carbon nitride
      nanosheets are synthesized by melamine carbonization and employed for Cr
      speciation in water and food real samples. Total Cr(VI) and Cr(VI) are assessed
      based on the quenching of the fluorescence of nanosheets by Cr(VI).

PMID- 29594608
TI  - Electrochemiluminescence based detection of microRNA by applying an amplification
      strategy and Hg(II)-triggered disassembly of a metal organic frameworks
      functionalized with ruthenium(II)tris(bipyridine).
AB  - An electrochemiluminescence (ECL) biosensor is described for the detection of
      microRNA (miRNA-155) based on tris(bipyridine)ruthenium(II) functionalized metal
      organic framework (RuMOF) materials. The material was prepared by a solvothermal
      method and was found to be stable even in acidic solution. However, it is
      selectively and sensitively disassembled by Hg(II) ions, resulting in the release
      of large quantities of Ru(II)(bpy)3 ions, which produces a strong ECL signal. In
      view of the ion-selective disassembly and release and strand displacement
      process, an ultrasensitive ECL sensing method was established for detection of
      microRNAs. In the presence of the target, the hairpin structure of H1 can open
      and hybridize with the hairpin probe H2 to form a more stable H1-H2 duplex
      structure than the H1-target hybrid. The target of hybridization to H1 was
      immediately freed from the structure and the released target re-entered the new
      hairpin assembly target recovery process. The remaining H2 single fragment can
      bind to the I-RuMOFs-conjugates. The more hairpin probes H1, the more I-RuMOFs
      conjugates load the DNA fragments, leading to the signal amplification. The
      method works in the 0.8 f. to 1.0 nM miRNA-155 concentration range and has a
      detection limit of 0.3 fM. The assay is sensitive, fairly specific and remarkably
      stable. In our perception, it offers an attractive tool for the sensitive
      detection of microRNAs in clinical samples. Graphical abstract An
      electrochemiluminescence (ECL) based biosensor is described for the detection of
      microRNA (miRNA-155) based on the use of a metal organic framework functionalized
      with ruthenium(II)tris(bipyridine) that was deposited on a glassy carbon
      electrode (GCE) modified with gold nanoparticles.

PMID- 29594609
TI  - Reliability of a commercially available heterochromatic flicker photometer, the
      MPS2, for measuring the macular pigment optical density of a Japanese population.
AB  - PURPOSE: The macular pigment optical density (MPOD) of a Japanese population was
      measured using a commercially based heterochromatic flicker photometer, the
      Macular Pigment Screener (MPS2). The objective of the study was to evaluate the
      accuracy and test-retest reliability of the MPS2 in Asian pigmented eyes. STUDY
      DESIGN: Experimental study to validate the medical instrument in humans. METHODS:
      Twenty-four healthy Japanese participants with no systemic or eye diseases (men:
      13, women: 11; mean [SD] age 38.6 [10.9 years]) were included. The concordance of
      the MPOD, obtained using the MPS2 and Macular Metrics II (MM2), and the test
      retest reliability were examined. RESULTS: Determination of the MPOD was
      unsuccessful in 1 participant; thus, the MPOD of 23 participants was analyzed.
      The mean (SD) MPOD measured with the detail-mode of the MPS2 was 0.63 (0.18) and
      with that of the MM2, it was 0.72 (0.23). The former was significantly lower than
      the latter (P = .003, paired t test). The MPOD measured with the MPS2 and the MM2
      showed good concordance (r = 0.79, P < .001, Pearson product moment correlation).
      Bland-Altman analyses showed no systematic errors between the MPS2 and the MM2.
      The intraclass correlation coefficient over 5 measurement times with the detail
      mode of the MPS2 was 0.80, and the mean coefficient of variation was 9.4%.
      CONCLUSION: The high concordance with the MM2 and good test-retest reliability
      found by this study suggest that the MPS2 is acceptable for use in a Japanese
      population. However, the mean MPOD yielded by the MPS2 was significantly lower
      than that yielded by the MM2. Therefore, the MPS2 and MM2 are not interchangeable
      in a single study.

PMID- 29594610
TI  - Extended field imaging using swept-source optical coherence tomography
      angiography in retinal vein occlusion.
AB  - PURPOSE: To evaluate the degree of ischemia in eyes with retinal vein occlusion
      (RVO) using swept-source optical coherence tomography angiography (SS-OCTA) with
      the extended field imaging (EFI) technique, which extends the area encompassed by
      SS-OCTA by scanning through trial frames fitted with a +20-diopter lens. STUDY
      DESIGN: Retrospective observational study. METHODS: Twenty-three consecutive eyes
      of 22 patients with RVO underwent 12 * 12 mm SS-OCTA imaging both with and
      without EFI for determination of extension rate. Two graders blinded to the
      clinical data evaluated the degree of retinal ischemia in paired EFI-SS-OCTA and
      fluorescein angiography (FA) images, and the concordance rates between the grades
      were statistically examined. RESULTS: One EFI-SS-OCTA image was not successfully
      obtained due to motion artifacts caused by the patient's poor central vision,
      while SS-OCTA images without EFI were captured in all 23 eyes. The average
      extension rate of EFI-SS-OCTA over SS-OCTA was 1.39 +/- 0.06 and the average
      scanning area was enlarged by 76.4%. Two graders evaluated the degree of retinal
      ischemia by measuring nonperfusion areas as the sum of disc areas/diameters.
      Although their assessments of the EFI-SS-OCTA images were in complete agreement
      (Cohen's Unweighted Kappa coefficient = 1.00), concordance using FA images was
      only moderate (Cohen's Unweighted Kappa coefficient = 0.60). CONCLUSION: EFI-SS
      OCTA noninvasively produces wider field images of retinal vasculature with one
      capture and provides resolution sufficient to accurately evaluate retinal
      capillary nonperfusion in RVO.

PMID- 29594611
TI  - Phenotypic plasticity may help lizards cope with increasingly variable
      temperatures.
AB  - Temperature variability is predicted to increase in the coming century due to
      climate change. However, the biological impact of increased temperature
      variability on animals remains largely unexplored. Here, we experimentally
      exposed gravid viviparous lizards (Eremias multiocellata) to two thermal
      environments [constant daily maximum (CDM) versus variable daily maximum (VDM)
      treatment with the same average temperature] to address maternal and offspring
      responses to increased variability in ambient temperature. Females from the VDM
      treatment delayed parturition, but produced similar litter sizes and litter
      masses as did CDM females. Offspring from the VDM treatment selected higher body
      temperatures, had higher metabolic rates and higher growth rates, and grew to a
      similar size as those from the CDM treatment despite having a shorter growth
      period prior to hibernation. Therefore, phenotypic plasticity may be critical for
      lizards to respond effectively to climate change, and its role in responding to
      increasingly variable temperatures warrants further attention.

PMID- 29594612
TI  - Correction to: System productivity alters predator sorting of a size-structured
      mixed prey community.
AB  - There was an error in the abstract of the original publication. The 9th sentence
      of abstract should be:"Our results are inconsistent with predictions about the
      sorting effects of predators across productivity gradients because the more
      resistant prey dominated at low productivity."

PMID- 29594613
TI  - Mosquito responses to trait- and density-mediated interactions of predation.
AB  - Mosquito and predatory larvae often share the same habitat. Predators may
      influence mosquito prey populations through both lethal effect and non-lethal
      pathways. A series of experimental manipulations were used to distinguish between
      lethal (density-mediated interaction) and non-lethal (trait-mediated interaction)
      effects in a model system comprised of invasive prey mosquito, Aedes aegypti, and
      a predatory mosquito Toxorhynchites rutilus. Treatments with predators present or
      manipulations mimicking daily mortality (density reduction) reduced developmental
      time and recruitment to the adult stage. Daily records of adult survival of A.
      aegypti showed that exposure to predators during the juvenile stage shortened the
      lifespan of adults. This was also observed in treatments, where A. aegypti were
      replaced at the rate of consumption by T. rutilus. In contrast, numerical
      reductions in A. aegypti that mimicked daily rate of predation led to adults with
      the longest lifespan. These observations suggest strong effects of density and
      trait-mediated interactions in the influence of predators on mosquito biology
      relevant to their ability to transmit pathogens. These results have potentially
      important implications for disease control strategies. The primary approach to
      reduce risk of mosquito-borne diseases is through population reduction of the
      vectors. We show an unanticipated benefit of biological control by predation for
      the control of juvenile stages of mosquitoes. Specifically, mosquitoes that are
      exposed to predators but survive to adulthood will have compromised life
      expectancy, a key parameter in determining risk of disease transmission.

PMID- 29594614
TI  - Changes in plant growth and seed production in wild lima bean in response to
      herbivory are attenuated by parasitoids.
AB  - Lima bean plants (Phaseolus lunatus) exhibit compensatory growth responses to
      herbivory. Among the various factors that have been identified to affect plant
      compensatory growth are the extent and type of tissue damage, the herbivore's
      feeding mode and the time of damage. Another factor that can greatly impact plant
      responses to herbivory, but has been largely ignored in previous studies, is the
      action of parasitoids. In most cases, parasitoids halt or slow down the
      development of herbivorous hosts, which, can result in decreased leaf damage,
      thereby affecting plant responses and ultimately plant fitness. Here, we
      investigated the effects of two koinobiont parasitoids on the amount of leaf
      damage inflicted by the Southern armyworm Spodoptera latifascia to wild lima
      bean, and the consequences of this for plant growth and seed production in the
      field. We specifically tested the hypothesis that the action of parasitoids will
      reduce plant damage and that this reduction will alter plant growth responses and
      seed production. Indeed, we found that in the presence of parasitoids plants
      suffered less damage than plants with only herbivores. As a consequence,
      compensatory growth was reduced and more and heavier seeds were produced earlier
      in the season, compared to plants exposed to only herbivores.

PMID- 29594615
TI  - Two-dimensional MoS2 as a nano-binder for ssDNA: Ultrasensitive aptamer based
      amperometric detection of Ochratoxin A.
AB  - Two-dimensional (2D) MoS2 is found to possess different affinities for ssDNA and
      dsDNA. This finding is exploited in an amperometric aptamer-based method for the
      determination of the mycotoxin ochratoxin A (OTA). Initially, a dsDNA probe
      (formatted through the hybridization of OTA-aptamer with an auxiliary DNA) is
      self-assembled on a gold electrode. Upon introduction of OTA, it will bind to the
      aptamer and cause the unwinding of dsDNA, while the auxiliary DNA (with single
      stranded structure) remains on the electrode. Since the affinity of 2D MoS2 for
      ssDNA is considerably larger than that for dsDNA, it will be adsorbed on the
      electrode by binding to the auxiliary DNA. Notably, 2D MoS2 possesses peroxidase
      like activity. Hence, it can catalyze the amplification of electrochemical signal
      of the hydroquinone/benzoquinone redox system. Under optimal conditions, the
      amperometric signal (best measured at -0.2 V vs. SCE) increases with increasing
      OTA concentration in the range from 0.5 pg.mL-1 to 1.0 ng.mL-1, with a lower
      detection limit of 0.23 pg.mL-1. The method was applied to the determination of
      OTA in spiked red wine. Graphical abstract Herein we construct a convenient
      electrochemical aptasensor for sensitive monitor of ochratoxin A by using 2D MoS2
      as a nano-binder to catalyze the amplification of electrochemical signal from
      hydroquinone/benzoquinone system.

PMID- 29594616
TI  - 3-Dimensional hollow graphene balls for voltammetric sensing of levodopa in the
      presence of uric acid.
AB  - The development of novel nanomaterials brings new opportunity and challenge for
      high sensing detection of biomolecules. The authors describe the preparation of 3
      dimentional hollow graphene balls (3D HGBs) using nickel nanoparticles (Ni-NPs)
      as the template. The Ni-NPs were synthesized by chemical reduction of nickel
      chloride and then graphene was coated onto their surface via carburization and
      carbonization. After etching Ni-NPs, 3D HGBs with few layers and a typical size
      of 100 nm were obtained. They were sprayed onto indium tin oxide glass to obtain
      a working electrode for electrochemical determination of levodopa in the presence
      of uric acid. Due to the unique hollow porous structure of the 3D HGBs, the
      electrode exhibits a sensitivity of 0.69 MUA.MUM-1.cm-2 and a 1 MUM limit of
      detection. It is selective, reproducible and stable. It was applied to the
      determination of levodopa in spiked human plasma samples and it is of potential
      use in clinical research. Graphical abstract Schematic presentation of the
      preparation of 3-dimensional hollow graphene balls (HGBs) by using nickel
      nanoparticles as a template that can be removed by etching. The HGBs were sprayed
      onto indium tin oxide (ITO) glass to obtain a working electrode that has a
      sensitivity of 0.69 MUA?MUM-1.cm-2 and a 1 MUM limit of detection for the
      determination of levodopa.

PMID- 29594617
TI  - Fluorescence polarization gene assay for HIV-DNA based on the use of dendrite
      modified gold nanoparticles acting as signal amplifiers.
AB  - The authors describe a fluorescence polarization assay for HIV-DNA. It is based
      on the use of gold nanoparticles (AuNPs) modified with DNA dendritic
      macromolecules that act as signal amplifiers. In the presence of HIV-DNA, the
      AuNP-DNA dendritic macromolecules and fluorescently labeled DNA probe combine
      with HIV-DNA in a sandwich format to form a conjugate. This reaction slows down
      the rotational speed of the labeled DNA probe because of the increase of
      molecular weight and volume. This increases fluorescence polarization and the
      sensitivity of the system. The relative fluorescence polarization values increase
      linearly in the 150 pM to 6 nM HIV-DNA concentration range, with a 73 pM
      detection limit. The results show this amplification strategy to be most useful
      for ultrasensitive determination of oligonucleotides by means of fluorescence
      polarization. Graphical abstract Schematic of a novel fluorescence polarization
      assay for the HIV-DNA. Ultrasensitive detection is accomplished by using AuNP-DNA
      dendritic macromolecules as signal amplification factor.

PMID- 29594618
TI  - Mobile Phone Questionnaires for Sexual Risk Data Collection Among Young Women in
      Soweto, South Africa.
AB  - Recall and social desirability bias undermine self-report of paper-and-pencil
      questionnaires. Mobile phone questionnaires may overcome these challenges. We
      assessed and compared sexual risk behavior reporting via in-clinic paper-and
      pencil and mobile phone questionnaires. HVTN 915 was a prospective cohort study
      of 50 adult women in Soweto, who completed daily mobile phone, and eight
      interviewer-administered in-clinic questionnaires over 12 weeks to assess sexual
      risk. Daily mobile phone response rates were 82% (n = 3486/4500); 45% (n =
      1565/3486) reported vaginal sex (median sex acts 2 (IQR: 1-3)) within 24 h and
      40% (n = 618/1565) consistent condom. Vaginal sex reporting was significantly
      higher via mobile phone across all visits (p < 0.0001). There was no significant
      difference in condom use reporting by mobile phone and in-clinic paper-based
      questionnaires across all visits (p = 0.5134). The results show high adherence
      and reporting of sex on the mobile phone questionnaire. We demonstrate
      feasibility in collecting mobile phone sexual risk data.

PMID- 29594619
TI  - Colorimetric detection of genetically modified organisms based on exonuclease III
      assisted target recycling and hemin/G-quadruplex DNAzyme amplification.
AB  - An isothermal colorimetric method is described for amplified detection of the
      CaMV 35S promoter sequence in genetically modified organism (GMO). It is based on
      (a) target DNA-triggered unlabeled molecular beacon (UMB) termini binding, and
      (b) exonuclease III (Exo III)-assisted target recycling, and (c) hemin/G
      quadruplex (DNAzyme) based signal amplification. The specific binding of target
      to the G-quadruplex sequence-locked UMB triggers the digestion of Exo III. This,
      in turn, releases an active G-quadruplex segment and target DNA for successive
      hybridization and cleavage. The Exo III impellent recycling of targets produces
      numerous G-quadruplex sequences. These further associate with hemin to form
      DNAzymes and hence will catalyze H2O2-mediated oxidation of the chromogenic
      enzyme substrate ABTS2- causing the formation of a green colored product. This
      finding enables a sensitive colorimetric determination of GMO DNA (at an
      analytical wavelength of 420 nm) at concentrations as low as 0.23 nM. By taking
      advantage of isothermal incubation, this method does not require sophisticated
      equipment or complicated syntheses. Analyses can be performed within 90 min. The
      method also discriminates single base mismatches. In our perception, it has a
      wide scope in that it may be applied to the detection of many other GMOs.
      Graphical abstract An isothermal and sensitive colorimetric method is described
      for amplified detection of CaMV 35S promoter sequence in genetically modified
      organism (GMO). It is based on target DNA-triggered molecular beacon (UMB)
      termini-binding and exonuclease III assisted target recycling, and on hemin/G
      quadruplex (DNAzyme) signal amplification.

PMID- 29594620
TI  - A chromium(III) oxide-coated steel wire prepared by arc ion plating for use in
      solid-phase microextraction of aromatic hydrocarbons.
AB  - The authors introduce an arc ion plating method for the deposition of chromium
      oxide (Cr2O3) on a steel wire substrate, and its use as a coating for solid phase
      microextraction. The coating has a micro- and nano-scaled structure after
      annealing at 700  degrees C. It is found that Cr2O3 exhibits a good extraction
      capability for the aromatic hydrocarbons naphthalene, anthracene, fluorene,
      fluoranthene, and biphenyl. Following desorption by high temperature at 300 
      degrees C, the analytes were quantified by gas chromatography (GC). The limits of
      detection are in the range between 20 and 200 ng.L-1, and calibration plots are
      linear within a wide range (0.2 to 400 MUg.L-1). The coating has excellent
      mechanical properties, with a hardness is as high as 31.7 GPa, and the adhesion
      strength between coating and substrate reaches 20.1 N (corresponding to the
      critical Hertzian contact stress of 10 GPa). This, along with the chemical and
      thermal stability of the Cr2O3 coating, endows the wire with a long operational
      life. It was used for at least 100 times without any obvious decline of
      extraction capability. Graphical abstract An arc ion plating method was
      introduced for the deposition of chromium oxide (Cr2O3) on a steel wire
      substrate, and its use as a coating for solid phase microextraction with high
      mechanical strength, stability, and long operational lifetime.

PMID- 29594621
TI  - An amino-functionalized magnetic framework composite of type Fe3O4-NH2@MIL
      101(Cr) for extraction of pyrethroids coupled with GC-ECD.
AB  - An amino-functionalized magnetic framework composite of type Fe3O4-NH2@MIL
      101(Cr) was synthesized using a solvothermal method. The material was
      characterized by scanning electron microscopy, X-ray diffraction, Fourier
      transform infrared spectroscopy, nitrogen adsorption, and magnetometry. The
      composite combines the advantages of amino-modified Fe3O4 and MIL-101(Cr). The
      presence of amino groups facilitates the fairly specific adsorption of
      pyrethroids. The composite was employed as a sorbent for magnetic solid phase
      extraction of five pyrethroids from environmental water samples. Following
      desorption with acidified acetone, the pyrethroids were quantified by gas
      chromatography with electron capture detection. The detection limits for
      bifenthrin, fenpropathrin, lambda-cyhalothrin, permethrin, and deltamethrin range
      from 5 to 9 pg.mL-1. The method is rapid, accurate, and highly sensitive. The
      molecular interactions and free binding energies between MIL-101(Cr) and the five
      pyrethroids were calculated by means of molecular docking. Graphical abstract A
      novel functionalized magnetic framework composite of type Fe3O4-NH2@MIL-101(Cr)
      was synthesized. It was applied as a sorbent for magnetic solid phase extraction
      of pyrethroids prior to their quantitation by gas chromatography with electron
      capture detection. The molecular interactions of analytes and MIL-101(Cr) were
      studied.

PMID- 29594622
TI  - Intrinsic peroxidase-like activity of rhodium nanoparticles, and their
      application to the colorimetric determination of hydrogen peroxide and glucose.
AB  - The intrinsic peroxidase-like activity of rhodium nanoparticles (RhNPs) and their
      use as catalytic labels for sensitive colorimetric assays is presented. RhNPs
      catalyze the oxidation of the peroxidase substrate 3,3,5,5-tetramethylbenzidine
      (TMB) in the presence of H2O2 to produce a blue reaction product with a maximum
      absorbance at 652 nm. Kinetic studies show catalysis to follow Michaelis-Menten
      kinetics and a "ping-pong" mechanism. The calculated kinetic parameters indicate
      high affinity of RhNPs for both the substrate TMB and H2O2. In fact, they are
      better than other peroxidase mimicking nanomaterials and even the natural enzyme
      horseradish peroxidase. On the other hand, RhNPs exhibit no reactivity towards
      saccharides, thiols, amino acids and ascorbic acid. Based on these findings, a
      sensitive and selective colorimetric method was worked out for the determination
      of H2O2 in real samples with a linear response in the 1-100 MUM concentration
      range. By employing glucose oxidase, the glucose assay has a linear range that
      covers the 5 to 125 MUM glucose concentration range. The detection limits are
      <0.75 MUM for both species. The methods were applied to the determination of H2O2
      in spiked pharmaceutical formulations, and of glucose in soft drinks and blood
      plasma. Figures of merit include (a) good accuracy (with errors of <6%), (b) high
      recoveries (96.5-103.7%), and (c) satisfactory reproducibility (<6.3%). Graphical
      abstract Rhodium nanoparticles catalyze the oxidation of 3,3,5,5
      tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue reaction
      product. The effect is exploited in photometric assays for hydrogen peroxide and
      glucose.

PMID- 29594624
TI  - The influence of fatty acid supply and aldehyde reductase deletion on
      cyanobacteria alkane generating pathway in Escherichia coli.
AB  - Cyanobacteria alkane synthetic pathway has been heterologously constructed in
      many microbial hosts. It is by far the most studied and reliable alkane
      generating pathway. Aldehyde deformylating oxygenase (i.e., ADO, key enzyme in
      this pathway) obtained from different cyanobacteria species showed diverse
      catalytic abilities. This work indicated that single aldehyde reductase deletions
      were beneficial to Nostoc punctiforme ADO-depended alkane production in
      Escherichia coli even better than double deletions. Fatty acid metabolism
      regulator (FadR) overexpression and low temperature increased C18:1 fatty acid
      supply, and in turn stimulated C18:1-derived heptadecene production, suggesting
      that supplying ADO with preferred substrate was important to overall alkane yield
      improvement. Using combinational methods, 1 g/L alkane was obtained in fed-batch
      fermentation with heptadecene accounting for nearly 84% of total alkane.

PMID- 29594623
TI  - Colorimetric determination of ferrous ion via morphology transition of gold
      nanorods.
AB  - A colorimetric method is described for the determination of ferrous ion (Fe2+)
      with high sensitivity and selectivity. The method is based on catalytic etching
      of gold nanorod (NR). In an acid condition, Fe2+ reacts with H2O2 to produce
      superoxide radical (O2*-) that etches gold NRs from the low energy surface along
      the longitudinal direction preferentially. As a result, the changes in the
      absorption spectrum and color of gold NR can be measured and also can be detected
      visually. Under the optimal conditions, the assay has very low detection limit
      (13.5 nM) and a linear response in a concentration range of 75 to 1 MUM. The
      method was applied to the determination of Fe2+ in spiked samples of fetal bovine
      serum and also transferred to a kind of test stripe for use in fast practical
      applications. A unique colorimetric sensing method is demonstrated for the
      colorimetric detection of Fe2+, again based on the oxidation of gold nanorods
      which leads to the blue-shift of the absorption. Graphical abstract A unique
      colorimetric sensing method was shown for the colorimetric detection of Fe2+.
      Fe2+reacts with H2O2 to generate superoxide radical that oxidize gold nanorods.
      This leads to a color change from blue-green to pink.

PMID- 29594625
TI  - Colorimetric theophylline aggregation assay using an RNA aptamer and non
      crosslinking gold nanoparticles.
AB  - The authors are presenting a rapid method for the determination of theophylline
      using unique non-crosslinking gold nanoparticle (AuNP) aggregation. An RNA
      aptamer against theophylline is firstly split into two RNA fragments which then
      interact with bare AuNPs. The two RNA probes cause an enhancement of the salt
      tolerance of AuNPs. However, in the presence of theophylline, the RNA probes form
      a complex with theophylline so that less RNA probes are available to protect the
      AuNPs from salt-induced aggregation. Theophylline induced aggregation of AuNPs is
      accompanied by a color change from red to blue. The color change can be detected
      visually and via UV-vis absorptiometry by ratioing the absorbances at 650 and 520
      nm. The ratio increases linearly in the 0.1 to 20 MUM theophylline concentration
      range, with a 67 nM limit of detection. The method is highly sensitive and
      selective. Graphical abstract Single-stranded split RNA aptamers (R1 and R2)
      protect gold nanoparticles (AuNPs) from salt-induced non-crosslinking
      aggregation. After recognition of theophylline by the RNA probe, the unprotected
      AuNPs aggregate and undergo a color change from red to blue, and this is used to
      quantify the theophylline concentration.

PMID- 29594626
TI  - A fluorescent DNA based probe for Hg(II) based on thymine-Hg(II)-thymine
      interaction and enrichment via magnetized graphene oxide.
AB  - The authors describe a fluorometric assay for the determination of Hg(II). A
      naphthalimide derivative is used as a label for a thymine (T) rich ssDNA, and
      graphene oxide magnetized with Fe3O4 nanoparticles acts as a quencher and
      preconcentrators. In the absence of Hg(II), the labeled ssDNA does not separate
      from the magnetized graphene oxide. As a result, fluorescence is fully quenched.
      In the presence of Hg(II), a T-Hg(II)-T link is formed dues to the highly
      affinity between T and Hg(II). Hence, fluorescence is restored. The assay has a
      linear response in the 1.0 to 10.0 nM Hg(II) concentration range, and a 0.65 nM
      detection limit. The method is selective and sensitive. It was applied to the
      analysis of spiked environmental water samples, and data agreed well with those
      obtained by atomic fluorescence spectrometry. Graphical abstract Strategy of a
      fluorescent probe for detecting Hg(II). The method has a 0.65 nM detection limit
      and is selective. MGO: magnetized graphene oxide, AHN: a fluorescent derivative
      of naphthalimide.

PMID- 29594627
TI  - Agriculture and elevation are the main factors for Pampasic stream habitat and
      water quality.
AB  - Streams of the Pampasic plain in Southeastern South America are ecosystems
      affected by both water pollution and habitat alteration mainly due to
      agricultural activity. Water quality is influenced by the quality of habitats and
      both depend on land use and watershed morphology. The objective of this study was
      to determine the relationship between the variables of four factors: (1) the
      morphology of the watershed, (2) land use in the watershed, (3) river habitat,
      and (4) water quality of wadeable streams in Uruguay, as well as to determine the
      most representative variables to quantify such factors. We studied 28 watersheds
      grouped into three ecoregions and four principal activities, which generated
      seven zones with three to five streams each. Correlations between the variables
      of each factor allowed reducing the total number of variables from 57 to 32 to
      perform principal component analyses (PCA) by factor, reducing the number of
      variables to 18 for a general PCA. The first component was associated with water
      quality and elevation. The second was associated with the stream and watershed
      size, the third with habitat quality, and the fourth to the use of neighboring
      soils and objects in the channel. Our results indicate that agricultural
      intensity and elevation are the main factors associated with the habitat and
      water quality of these lowland streams. These factors must be especially
      considered in the development of water quality monitoring programs.

PMID- 29594628
TI  - An ultrasensitive conformation-dependent colorimetric probe for the detection of
      mercury(II) using exonuclease III-assisted target recycling and gold
      nanoparticles.
AB  - An ultrasensitive conformation-dependent colorimetric assay has been developed
      for the detection of mercury(II) ions. It is based on the use of exonuclease III
      (Exo III)-assisted target recycling and gold nanoparticles (AuNPs). In the
      absence of Hg(II), the hairpin-shaped DNA probe (H-DNA) binds to AuNPs and
      stabilizes them in solutions of high ionic strength. In the presence of Hg(II),
      on the other hand, the sticky termini of the H-DNA form a rigid DNA duplex stem
      with a blunt 3'-terminus. Thus, Exo III is activated as a biocatalyst for
      selective and stepwise removal of mononucleotides from the 3'-terminus of the H
      DNA. As a result, Hg(II) is released from the T-Hg(II)-T complexes. The guanine
      rich sequences released from the H-DNA are then self-assembled with potassium ion
      to form a stable G-quadruplex conformation. In solutions of high ionic strength,
      this results in aggregation of AuNPs and a color change from red to blue which
      can be seen with bare eyes. The method is highly sensitive and selective. It has
      a linear response in the 10 pM to 100 nM Hg(II) concentration range, and the
      detection limit is as low as 3.2 pM (at an S/N ratio of 3). The relative standard
      deviation at a level of 0.5 nM of Hg(II) is 4.9% (for n = 10). The method was
      applied to the detection of Hg(II) in spiked environment water samples, with
      recoveries ranging from 92% to 106%. Graphical abstract A conformation-dependent
      colorimetric system was fabricated for label-free detection of mercury(II) by
      utilizing exonuclease III(Exo III)-assisted target recycling and gold
      nanoparticles (AuNPs).

PMID- 29594629
TI  - Synthesis of hybrid magneto-plasmonic nanoparticles with potential use in
      photoacoustic detection of circulating tumor cells.
AB  - This article describes a novel synthetic route to obtain hybrid nanostructures
      that combine the plasmonic properties of gold nanorods with the magnetic
      properties of iron oxide nanoparticles in a robust silica nanostructure. The
      silica matrix enhances the physico-chemical stability of the nanostructure and
      preserves its magneto-plasmonic properties by avoiding the interface between gold
      and iron oxide. In addition, the magneto-plasmonic features of the nanohybrids
      can be tuned due to the independent synthesis of each component. The magnetic and
      plasmonic properties of these nanostructures can potentially enhance the
      photoacoustic detection of circulating tumor cells. Graphical abstract Schematic
      presentation of a hybrid magneto-plasmonic nanoparticle with an Au@Fe3O4@SiO2
      core-satellite-shell arrangement. The magnetic and plasmonic responses of this
      kind of nanostructure enable magnetic trapping and photoacoustic detection of
      circulating tumor cells.

PMID- 29594630
TI  - A voltammetric immunosensor for clenbuterol based on the use of a MoS2-AuPt
      nanocomposite.
AB  - An ultrasensitive immunosensor for the direct detection of the illegally used
      livestock feed clebuterol (CLB) is described. It is based on the use of a glassy
      carbon electrode modified with an MoS2-AuPt nanocomposite and on biotin
      streptavidin interaction. The use of MoS2-AuPt accelerates electron transfer, and
      this leads to a sharp increase in the electrochemical signal for the
      electrochemical probe hydrogen peroxide. Differential pulse voltammetry was used
      to record the current signal at a peak potential of -0.18 V (vs SCE). Under
      optimal conditions, the electrode has a linear response in the 10 pg.mL-1 to 100
      ng.mL-1 CLB concentration range and a 6.9 pg.mL-1 detection limit (based on the
      3sigma criterium). This immunosensor is sensitive, highly specific and acceptably
      reproducible, and thus represents a valuable tool for the determination of CLB in
      pork. Graphical abstract Schematic of a voltammetric immunosensor for the
      determination of clenbuterol (CLB) based on the use of a nanocomposite prepared
      from molybdenum disulfide and a gold-platinum alloy (MoS2-AuPt), and making use
      of the biotin-streptavidin system.

PMID- 29594631
TI  - Microfluidic electrophoretic non-enzymatic kanamycin assay making use of a
      stirring bar functionalized with gold-labeled aptamer, of a fluorescent DNA
      probe, and of signal amplification via hybridization chain reaction.
AB  - The authors describe an enzyme-free aptamer-based assay for the determination of
      the model antibiotic kanamycin (Kana). The method is making use of (a)
      microfluidic chip electrophoresis; (b) a stirring bar carrying a gold-labeled
      aptamer probe, and (c) the hybridization chain reaction (HCR) for signal
      amplification. Firstly, a stirring bar (length: 1 cm; diameter: 0.2 mm) was
      modified with a large amount of duplex DNA and then hybridized with aptamer and
      its partially complementary chains (cDNA). In the presence of Kana, the binding
      between the Kana and aptamer unwinds the duplex structures and releases a
      corresponding amount of cDNA into the supernatant. The released cDNA triggers the
      HCR in the presence of H1 and H2 DNA hairpin to produce a large amount of duplex
      DNA chains with different lengths. At the same time, the amounts of H1 and H2 are
      reduced. The decreased signal of H1/H2 after several HCR cycles can be used to
      quantify kana in the 1 pg.mL-1 to 10 ng.mL-1, with a detection limit of 0.29
      pg.mL-1. The signal is generated by reading the fluorescence, best at
      excitation/emission maxima of 470/525 nm. The whole detection process takes 3 min
      only. The assay was employed to the detection of Kana in spiked milk and fish
      samples. Results are consistent with those of an enzyme linked immunosorbent
      assay. The assay has high throughput, high selectivity, and high amplification
      capability. Graphical abstract Schematic of a stirring bar functionalized with
      gold-labeled aptamer acting as the capture probe. It can capture the target and
      release primer simultaneously. The primer triggers the hybridization chain
      reaction inducing the consumption of H1 and H2. After a certain reaction time,
      the mixture is injected into the MCE platform for microfluidic electrophoretic
      separation and fluorometric detection.

PMID- 29594633
TI  - Impedimetric detection of cocaine by using an aptamer attached to a screen
      printed electrode modified with a dendrimer/silver nanoparticle nanocomposite.
AB  - The authors describe a highly sensitive method for the aptamer (Apt) based
      impedimetric determination of cocaine. The surface of a screen-printed electrode
      (SPE) was modified with a nanocomposite of dendrimer and silver nanoparticles
      (AgNPs). The cocaine-binding Apt was attached to a dendrimer/AgNP/SPE surface,
      forming a sensitive layer for the determination of cocaine. The incubation with
      the analyte resulted in the formation of a cocaine/Apt complex on the electrode
      surface. As a consequence, folding and conformational change in the aptamer
      structure was induced, this resulting in a change in the impedimetric signal. The
      aptaassay exhibits highly efficient sensing characteristics with a good linearity
      of 1 fmol L-1 to 100 nmol L-1 (with two linear ranges) and a limit of detection
      (LOD) of 333 amol L-1. Its excellent specificity and high sensitivity suggest
      that this kind of aptamer-based assay may be applied to detect other targets in
      this field. Graphical Abstract Designing of an aptaassay via immobilization of a
      functionalized aptamer with silver nanoparticle (AgNPs-Apt) on the modified
      screen-printed electrode (SPE) with dendrimer/silver nanoparticle nanocomposite
      (Den-AgNPs) for impedimetric detection of cocaine.

PMID- 29594632
TI  - Voltammetric sandwich immunoassay for Cronobacter sakazakii using a screen
      printed carbon electrode modified with horseradish peroxidase, reduced graphene
      oxide, thionine and gold nanoparticles.
AB  - The authors describe a sandwich-type of electrochemical immunoassay for rapid
      determination of the foodborne pathogen Cronobacter sakazakii (C. sakazakii).
      Polyclonal antibody against C. sakazakii (anti-C. sakazakii) and horseradish
      peroxidase were immobilized on a nanocomposite consisting of reduced graphene
      oxide, thionine and gold nanoparticles (AuNPs) that was placed on a screen
      printed carbon electrode (SPCE). Thionine acts as an electron mediator which also
      shortens the electron transfer pathway from the conjugated HRP to the electrode
      surface and amplifies the electrochemical signal. The AuNPs, in turn, improve the
      electron transfer rate and increase the surface area for capturing antibody. The
      morphologies of the electrodes were characterized by means of field emission
      scanning electron microscopy. The electrochemical performance of the immunoassay
      was evaluated by cyclic voltammetry and differential pulse voltammetry. Under
      optimal experimental conditions, the electrochemical immunoassay, best operated
      at a woking potential of -0.18 V (vs. Ag/AgCl) and scan rate of 20 mV/s has a
      linear response that covers the 8.8 * 104 to 8.8 * 108 CFU.mL-1 C. sakazakii
      concentration range, with a 1.0 * 104 CFU.mL-1 detection limit (at an S/N ratio
      of 3). The assay was applied to the detemination of C. sakazakii in spiked infant
      milk powder and gave recoveries ranging from 92.0 to 105.7%. Graphical abstract A
      sandwich-type electrochemical immunosensor was designed for C. sakazakii based on
      the use of rGO. TH, HRP, antibody and AuNPs were anchored on rGO. The
      nanocomposites were used as traces tag and H2O2 as enzyme substrates. AuNPs were
      modified on SPCE by electrodeposition.

PMID- 29594634
TI  - An "off-on" colorimetric and fluorometric assay for Cu(II) based on the use of
      NaYF4:Yb(III),Er(III) upconversion nanoparticles functionalized with branched
      polyethylenimine.
AB  - The authors describe an "off-on" colorimetric and fluorometric assay for the
      determination of Cu(II). It is based on the use of upconversion nanoparticles
      (UCNPs) of type NaYF4:Yb(III),Er(III) that were functionalized with branched
      polyethylenimine (BPEI). A color change from colorless to blue occurs within 2 s
      after addition of Cu(II) to a solution of the modified UCNPs. The color change
      can be visually detected at Cu(II) concentrations down to 80 MUM. The
      upconversion fluorescence of the modified UCNPs, measured at excitation
      wavelength of 980 nm, is reduced due to the predominant inner filter effect
      caused by the formation of the BPEI-Cu(II) complex. Normalized fluorescence
      intensity drops linearly in the 50 nM to 10 MUM Cu(II) concentration range, and
      the fluorometric detection limit is 45 nM. Both the color and the fluorescence
      are recovered on addition of EDTA. Excellent selectivity over other metal ions
      and anions is achieved. Graphical abstract Upconversion nanoparticles of type
      NaYF4:Yb,Er were functionalized with branched polyethylenimine (UCNP/BPEI) and
      used in an "off-on" colorimetric and fluorometric assay for Cu(II). The
      upconversion fluorescence is selectively quenched on addition of Cu(II), and this
      is accompanied by a rapid colorless-to-blue color switch. The colorimetric
      changes and quenched fluorescence can be reversed by adding EDTA.

PMID- 29594635
TI  - Reading, Trauma and Literary Caregiving 1914-1918: Helen Mary Gaskell and the War
      Library.
AB  - This article is about the relationship between reading, trauma and responsive
      literary caregiving in Britain during the First World War. Its analysis of two
      little-known documents describing the history of the War Library, begun by Helen
      Mary Gaskell in 1914, exposes a gap in the scholarship of war-time reading;
      generates a new narrative of "how," "when," and "why" books went to war; and
      foregrounds gender in its analysis of the historiography. The Library of
      Congress's T. W. Koch discovered Gaskell's ground-breaking work in 1917 and
      reported its successes to the American Library Association. The British Times
      also covered Gaskell's library, yet researchers working on reading during the war
      have routinely neglected her distinct model and method, skewing the research base
      on war-time reading and its association with trauma and caregiving. In the
      article's second half, a literary case study of a popular war novel demonstrates
      the extent of the "bitter cry for books." The success of Gaskell's intervention
      is examined alongside H. G. Wells's representation of textual healing. Reading is
      shown to offer sick, traumatized and recovering combatants emotional and
      psychological caregiving in ways that she could not always have predicted and
      that are not visible in the literary/historical record.

PMID- 29594636
TI  - Silver-doped CdS quantum dots incorporated into chitosan-coated cellulose as a
      colorimetric paper test stripe for mercury.
AB  - Silver-doped CdS quantum dots capped with mercaptoacetic acid were incorporated
      into a chitosan-coated filter paper to fabricate a colorimetric test stripe for
      mercury. Chitosan assisted in the stabilization of CdSAg QDs on cellulose and
      enhanced the analyte diffusion in the test stripe. Hg(II) ions were captured by
      mercaptoacetic acid on CdSAg, resulting in a visualized color change from yellow
      to deep brown. For enhanced sensitivity and quantitation with good
      reproducibility, the color intensity was recorded, transmitted to a smartphone
      camera and computed by the ImageJ software to provide a digital readout. The
      assay was rapid, simple, and selective for mercury as several potential
      interfering species provoked no signal response. The applicability of the sensing
      approach was demonstrated for the analysis of spiked Hg(II) ions in cosmetic
      cream with a detection limit of 124 MUM. Graphical abstract Schematic of a
      colorimetric test stripe consisting of silver-doped CdS quantum dots coated
      withmercaptoacetic acid and embedded into a chitosan matrix on paper. It enables
      mercury(II) to be visuallyquantified even in complex matrices such as cosmetics.

PMID- 29594637
TI  - Application of Genetic Algorithm (GA) Assisted Partial Least Square (PLS)
      Analysis on Trilinear and Non-trilinear Fluorescence Data Sets to Quantify the
      Fluorophores in Multifluorophoric Mixtures: Improving Quantification Accuracy of
      Fluorimetric Estimations of Dilute Aqueous Mixtures.
AB  - Excitation-emission matrix fluorescence (EEMF) and total synchronous fluorescence
      spectroscopy (TSFS) are the 2 fluorescence techniques that are commonly used for
      the analysis of multifluorophoric mixtures. These 2 fluorescence techniques are
      conceptually different and provide certain advantages over each other. The manual
      analysis of such highly correlated large volume of EEMF and TSFS towards
      developing a calibration model is difficult. Partial least square (PLS) analysis
      can analyze the large volume of EEMF and TSFS data sets by finding important
      factors that maximize the correlation between the spectral and concentration
      information for each fluorophore. However, often the application of PLS analysis
      on entire data sets does not provide a robust calibration model and requires
      application of suitable pre-processing step. The present work evaluates the
      application of genetic algorithm (GA) analysis prior to PLS analysis on EEMF and
      TSFS data sets towards improving the precision and accuracy of the calibration
      model. The GA algorithm essentially combines the advantages provided by
      stochastic methods with those provided by deterministic approaches and can find
      the set of EEMF and TSFS variables that perfectly correlate well with the
      concentration of each of the fluorophores present in the multifluorophoric
      mixtures. The utility of the GA assisted PLS analysis is successfully validated
      using (i) EEMF data sets acquired for dilute aqueous mixture of four biomolecules
      and (ii) TSFS data sets acquired for dilute aqueous mixtures of four carcinogenic
      polycyclic aromatic hydrocarbons (PAHs) mixtures. In the present work, it is
      shown that by using the GA it is possible to significantly improve the accuracy
      and precision of the PLS calibration model developed for both EEMF and TSFS data
      set. Hence, GA must be considered as a useful pre-processing technique while
      developing an EEMF and TSFS calibration model.

PMID- 29594638
TI  - A SERS method with attomolar sensitivity: a case study with the flavonoid
      catechin.
AB  - Making good use of interactions between analyte molecules and the metal
      nanoparticles is key to impact the detection limit in a surface-enhanced Raman
      scattering (SERS) based detections. SERS was applied to the analysis of catechin
      and it was found that the relative abundance of catechin in the sample to citrate
      capped AgNPs and the aggregation agent NaCl plays a critical role in the quality
      of detection. At a component volume ratio of 6:2:1 (catechin:AgNPs:NaCl),
      catechin can be detected at uM levels. When the ratio is 12:2:1, Raman signals
      are discernible even at the attomolar concentration level (10-18 M). Under these
      conditions, the SERS mechanisms and the force of laser tweezers function best.
      The extent of signal enhancement enabled an ultrasensitive and reproducible Raman
      spectroscopic determination of catechin. Graphical abstract At a component volume
      ratio of 6:2:1 (catechin:AgNPs:NaCl), catechin was detected at 10-3 M to 10-6 M.
      When the ratio was 12:2:1, the discernible concentration of catechin was found to
      reach the attomolar level (10-18 M).

PMID- 29594639
TI  - Determination of nickel(II) at nanomolar levels using iodide-responsive gold
      copper nanoparticles as colorimetric probes.
AB  - The authors present a colorimetric method for the quantification of Ni(II) at
      nanomolar levels. It is based on the use of iodide-responsive copper-gold
      nanoparticles (Cu-Au NPs) combined with the Ni(II)-catalyzed glutathione (GSH)
      oxygen reaction system. In the presence of Ni(II), the catalytic reaction between
      GSH and oxygen is can triggered. This leads to the formation of GSSG which is
      bulky and hinders the access of iodide to the surface of the Cu-Au NPs.
      Concomitantly, the color of the solution containing the Cu-Au NPs changes from
      gray to red. Based on these findings, a method was developed for the quantitation
      of Ni(II) that has a detection limit as low as 0.54 nM. This is 1-3 orders of
      magnitude lower than that of previously reported optical methods. The assay has
      excellent selectivity for Ni(II), is rapid, cost-effective, portable, and allows
      for bare eye observation. Conceivably the method is suitable for field detection
      of Ni(II) in biological, food, and environmental samples. Graphical Abstract A
      sensitive colorimetric strategy for Ni(II) through the combination of iodide
      responsive Cu-Au NPs with Ni(II)-catalyzed the oxidation of GSH by oxygen was
      presented.

PMID- 29594640
TI  - Gold nanoparticles functionalized with Pluronic are viable optical probes for the
      determination of uric acid.
AB  - The authors describe the preparation of gold nanoparticles (AuNPs) coated with
      poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)
      (Pluronic F-108) by reducing Au3+ to Au0 using curcumin, a natural and non-toxic
      food spice, in water of pH ~7 in the presence of F-108 and Ag+ ion. The coated
      AuNPs display strong resonance Rayleigh scattering (RRS) and fluorescence that
      results from the functionalization of the gold surface with curcumin and Pluronic
      F-108. The molar mass of Pluronic F-108 affects the particle size of the AuNPs
      formed, and small AuNPs are formed when using low molar weight F-108 that was
      purified by centrifugation or dialysis. The coated AuNPs were employed in an
      optical method for the determination of uric acid. The combination of uric acid
      with the AuNPs boosts both the RRS signal and the fluorescence of the AuNPs.
      However, higher concentrations of uric acid shift the fluorescence peak to
      shorter wavelengths. The method is simple, and fluorescence, best measured at
      excitation/emission wavelengths of 425/534 nm, increases linearly in the 50 MUM
      to 50 mM uric acid concentration range, with a 0.14 MUM detection limit which is
      lower than reported for other methods in the literature. Graphical abstract
      Pluronic F-108 capped gold nanoparticles prepared by reducing Au3+ to Au0 using
      curcumin can estimate uric acid in 50 MUM to 50 mM concentration range.

PMID- 29594641
TI  - Life Interference Due to Gambling in Three Canadian Provinces.
AB  - The gambling landscape among provinces in Canada is diverse. Yet, few studies
      have investigated provincial differences related to life interference due to
      gambling. The objectives of the current study were to examine: (1) provincial
      differences with regard to gambling types and (2) if gender, family history of
      gambling, and alcohol or drug use while gambling were related to an increased
      likelihood of life interference in three Canadian provinces. Data were drawn from
      the 2013 and 2014 cycles of the Canadian Community Health Survey from Manitoba,
      Saskatchewan, and British Columbia (n = 30,150). Analyses were conducted
      stratified by provinces and also combined using logistic regression models.
      Provincial differences were noted with individuals from British Columbia compared
      to Manitoba being less likely to play VLTs outside of casinos, play live horse
      racing at a track or off track, and participate in sports gambling. Those in
      Saskatchewan compared to Manitoba were more likely to play VLTs inside a casino.
      When examining all provinces combined, family history of gambling was associated
      with increased odds of life interference. Gender was not associated with life
      interference. Provincial differences were noted, which may be in part related to
      differences in gambling landscapes. Family history of gambling may have clinical
      relevance for understanding which individuals may be more likely to experience
      life interference due to gambling. Further research is needed to clarify the link
      between alcohol and drug use while gambling and life interference due to gambling
      as the models in the current research were likely underpowered.

PMID- 29594642
TI  - Room temperature LPG resistive sensor based on the use of a few-layer
      graphene/SnO2 nanocomposite.
AB  - A nanocomposite consisting of a few layers of graphene (FLG) and tin dioxide
      (SnO2) was prepared by ultrasound-assisted synthesis. The uniform SnO2
      nanoparticles (NPs) on the FLG were characterized by X-ray diffraction in terms
      of lattice and phase structure. The functional groups present in the composite
      were analyzed by FTIR. Electron microscopy (HR-TEM and FE-SEM) was used to study
      the morphology. The effect of the fraction of FLG present in the nanocomposite
      was investigated. Sensitivity, selectivity and reproducibility towards resistive
      sensing of liquid propane gas (LPG) was characterized by the I-V method. The
      sensor with 1% of FLG on SnO2 operated at a typical voltage of 1 V performs best
      in giving a rapid and sensitive response even at 27  degrees C. This proves that
      the operating temperature of such sensors can be drastically decreased which is
      in contrast to conventional metal oxide LPG sensors. Graphical abstract Schematic
      of a room temperature gas sensor for liquefied petroleum gas (LPG). It is based
      on the use of a few-layered graphene (1 wt%)/SnO2 nanocomposite that was
      deposited on an interdigitated electrode (IDEs). A sensing mechanism for LPG
      detection has been established.

PMID- 29594643
TI  - Ultrasensitive amperometric aptasensor for the epithelial cell adhesion molecule
      by using target-driven toehold-mediated DNA recycling amplification.
AB  - An amperometric aptasensor is reported for the electrochemical determination of
      the epithelial cell adhesion molecule (EpCAM). It is based on a combination of
      EpCAM-driven toehold-mediated DNA recycling amplification, the specific
      recognition of EpCAM aptamer, and its binding to EpCAM. Hairpin probe 1 (Hp1)
      with a toehold region was modified with a 5'-thiol group (5'-SH) and self
      assembled onto the surface of a gold electrode. Upon addition of EpCAM, the probe
      A (a 15-mer) is liberated from the aptamer/probe A complex and then hybridizes
      with the toehold domain of Hp1. This results in the exposure of another toehold
      for further hybridizing with hairpin probe 2 (Hp2) to displace probe A in the
      presence of Hp2 that was labeled with the electrochemical probe Methylene Blue
      (MB). Subsequently, liberated probe A is hybridized again with another Hp1 to
      start the next round of DNA recycling amplification by reusing probe A. This
      leads to the formation of plenty of MB-labeled DNA strands on the electrode
      surface and generates an amplified current. This 1:N probe-response amplification
      results in ultrasensitive and specific detection of EpCAM, with a 20 pg.mL-1
      detection limit. The electrode is highly stable and regenerable. It was
      successfully applied to the determination of EpCAM in spiked human serum, urine
      and saliva, and thus provides a promising tool for early clinical diagnosis.
      Graphical abstract Schematic illustration of the electrochemical detection for
      EpCAM. The method is based on aptamer-based recognition and EpCAM-driven toehold
      mediated DNA recycling amplification. Hp1: Hairpin probe 1; Hp2: Hairpin probe 2;
      MB: Methylene blue; MCH: 6-Mercapto-1-hexanol; EpCAM: Epithelial cell adhesion
      molecule.

PMID- 29594644
TI  - Non-osteogenic muscle hypertrophy in children with McArdle disease.
AB  - INTRODUCTION: McArdle disease is an inborn disorder of muscle glycogen metabolism
      that produces exercise intolerance, and has been recently associated with low
      values of lean mass (LM) and bone mineral content (BMC) and density (BMD) in
      affected adults. Here we aimed to study whether this bone health problem begins
      in childhood. METHODS: Forty children and adolescents were evaluated: 10 McArdle
      disease and 30 control children (mean age of both groups, 13 +/- 2y). Body
      composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase
      (CK) levels were determined in the patients as an estimate of muscle damage.
      RESULTS: Legs bone mass was significantly lower in patients than in controls (
      36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM
      values in the legs than controls, whereas no difference was found for fat mass.
      CK levels were positively associated with LM in McArdle patients. A correlation
      was found between LM and BMD variables in the control group but not in McArdle
      patients. CONCLUSION: We have identified a 'non-osteogenic muscle hypertrophy' in
      children with McArdle disease. This phenomenon warrants special attention since
      low osteogenesis at an early age predicts a high risk for osteoporosis later in
      life.

PMID- 29594646
TI  - Newborn screening for Pompe disease: impact on families.
AB  - Pompe disease (PD) is an autosomal recessive lysosomal storage disorder causing
      progressive glycogen accumulation in muscles, with variability in age of onset
      and severity. For infantile-onset PD (IOPD), initiation of early treatment can be
      life-saving; however, current newborn screening (NBS) technology cannot
      distinguish IOPD from late-onset PD (LOPD) without clinical workup. Therefore,
      families of LOPD infants diagnosed by NBS may now spend years or even decades
      aware of their illness before symptoms appear, creating a pre-symptomatic
      awareness phase with which the medical community has little experience. The
      present study examines the effects of receiving a positive NBS result for PD on
      families. In-depth qualitative interviews were conducted with mothers of nine
      children (three IOPD and six LOPD) diagnosed via NBS, exploring their
      experiences, understanding of PD, how they are coping, and what impact diagnosis
      is having on family life. Interviews were coded using MaxQDA v.12 and analyzed
      for thematic trends. While overall opinion of NBS was favorable, it is clear many
      of the concerns anticipated by HCPs, patients, and families regarding NBS for
      late-onset LSDs are being realized to varying degrees; LOPD families are becoming
      patients-in-waiting. Increased fear/anxiety and living with uncertainty
      (regarding diagnosis, their children's future, and when to start treatment) were
      predominant themes, with all families voicing considerable emotional reactions
      and varied social and healthcare support concerns. Coping strategies and
      psychosocial challenges are interpreted using Rolland & Williams' Family Systems
      Genetic Illness model. Recommendations for improvement in delivery of service, as
      well as families' advice for future parents and HCPs, are discussed.

PMID- 29594645
TI  - The role of suboptimal mitochondrial function in vulnerability to post-traumatic
      stress disorder.
AB  - Post-traumatic stress disorder remains the most significant psychiatric condition
      associated with exposure to a traumatic event, though rates of traumatic event
      exposure far outstrip incidence of PTSD. Mitochondrial dysfunction and suboptimal
      mitochondrial function have been increasingly implicated in several
      psychopathologies, and recent genetic studies have similarly suggested a
      pathogenic role of mitochondria in PTSD. Mitochondria play a central role in
      several physiologic processes underlying PTSD symptomatology, including abnormal
      fear learning, brain network activation, synaptic plasticity, steroidogenesis,
      and inflammation. Here we outline several potential mechanisms by which inherited
      (genetic) or acquired (environmental) mitochondrial dysfunction or suboptimal
      mitochondrial function, may contribute to PTSD symptomatology and increase
      susceptibility to PTSD. The proposed pathogenic role of mitochondria in the
      pathophysiology of PTSD has important implications for prevention and therapy, as
      antidepressants commonly prescribed for patients with PTSD have been shown to
      inhibit mitochondrial function, while alternative therapies shown to improve
      mitochondrial function may prove more efficacious.

PMID- 29594647
TI  - Pregnancy management and outcome in patients with four different
      tetrahydrobiopterin disorders.
AB  - INTRODUCTION: Inborn errors of tetrahydrobiopterin (BH4) biosynthesis or
      recycling are a group of very rare neurometabolic diseases. Following growing
      awareness and improved availability of drug treatment the number of patients with
      BH4 disorders reaching adulthood is constantly increasing. Pregnancy care of
      patients with these disorders is therefore a new challenge for clinicians.
      METHODS: This retrospective study summarises for the first time clinical and
      biochemical monitoring data of 16 pregnancies in seven women with different
      disorders of BH4 metabolism and evaluates treatment regimens before and during
      pregnancy in relation to the obstetrical outcome and paediatric follow-up.
      RESULTS: Worsening of pre-existing neurological symptoms or occurrence of new
      symptoms during pregnancy was not observed in most of the cases. Treatment
      regimens remained mostly unchanged. Pregnancies were not complicated by disease
      specific features. Organ abnormalities, miscarriage, prematurity, IUGR and
      chromosomal changes were occasionally reported, without showing any association
      with the standard drug treatment for BH4 deficiencies. CONCLUSION: Although our
      data on 16 pregnancies in seven patients did not present any association of
      standard drug treatment with an increased rate of pregnancy complications,
      abnormal obstetrical or paediatric outcome, an intensive clinical and biochemical
      supervision by a multidisciplinary team before, during and after the pregnancy in
      any BH4 deficiency is essential since available data on pregnancies in patients
      with BH4 deficiencies is limited.

PMID- 29594648
TI  - Identification and characterization of 40 novel hydroxymethylbilane synthase
      mutations that cause acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP), an autosomal dominant disorder due to the
      half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by
      acute neurovisceral attacks that are precipitated by factors that induce heme
      biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic
      test for AIP, and importantly, it permits the identification of asymptomatic
      family members for genetic counseling and avoidance of precipitating factors.
      Here, we report the identification of 40 novel HMBS mutations, including 11
      missense, four nonsense, 16 small insertions or deletions, eight consensus splice
      site mutations, and a complex insertion-deletion mutation in unrelated
      individuals with AIP. Prokaryotic expression of the missense mutations
      demonstrated that all mutants had <=5% of expressed wildtype activity, except for
      c.1039G>C (p.A347P), which had 51% residual HMBS activity but was markedly
      thermolabile. Of note, the mutation c.612G>T (p.Q204H) altered the last
      nucleotide of exon 10, which resulted in an alternative HMBS transcript with an
      in-frame nine base-pair deletion at the 3'-terminus of exon 10 (encoding protein
      Q204HDelta3). When expressed, Q204HDelta3 and an in-frame three base-pair
      deletion (c.639_641delTGC) had no detectable HMBS activity. Western blot analyses
      and mapping of the missense mutations on the human HMBS crystal structure
      revealed that mutations near the active site or at the dimerization interface
      resulted in stably expressed proteins, while most that altered surface residues
      resulted in unstable proteins, presumably due to improper protein folding. These
      studies identified novel pathogenic HMBS mutations and expanded the molecular
      heterogeneity of AIP.

PMID- 29594649
TI  - Gold nanoclusters as a quenchable fluorescent probe for sensing oxygen at high
      temperatures.
AB  - Gold nanoclusters (AuNCs) capped with lipoic acid (LA) or templated with bovine
      serum albumin (BSA) are shown to be viable fluorescent probes for oxygen (O2)
      which acts as a collisional quencher. Quenching of fluorescence, with its
      lifetimes in the order of 123 +/- 9 ns (LA) and 153 +/- 15 ns (BSA) (in aqueous
      solution), is best measured at excitation/emission wavelengths of 400/680 nm and
      375/650 nm respectively. It follows the Stern-Volmer model, whose quenching
      constants (Ksv) and quenching efficiencies (gamma) are 1400 M-1 and 0.52 for
      AuNC@LA and 4479 M-1 and 0.90 for AuNC@BSA. The probes were immobilized on a
      silica support and tested for response to O2 in gas phase using a commercial
      instrument. The effect of temperature on the fluorescence of AuNC@LA was studied
      in the range from 30 to 210  degrees C. Fluorescence intensity slightly decreases
      with temperature in the first heating cycle but remains constant in further
      cycles. The AuNC@LA were studied for their response to O2 in the temperature
      range from 30 to 100  degrees C, and even at 100  degrees C they respond to O2,
      with a Ksv that slightly drops with increasing temperature. Measuring in gas
      phase at 100  degrees C, the sensor has a detection limit of 3% (V/V) of O2 at a
      signal-to-noise ratio of 3. Graphical Abstract Gold-nanoclusters (AuNCs)
      fluorescence intensity (lambdaexc = 400 nm, lambdaem = 680 nm) remains constant
      from 30 to 210  degrees C and is quenched by O2 following a collisional
      mechanism. The Stern-Volmer constant (Ksv) slightly changes from 25  degrees C to
      100  degrees C (at least).

PMID- 29594650
TI  - Plasmonic DNA hotspots made from tungsten disulfide nanosheets and gold
      nanoparticles for ultrasensitive aptamer-based SERS detection of myoglobin.
AB  - A nanohybrid mediated SERS substrate was prepared by in-situ synthesis and
      assembly of gold nanoparticles (AuNPs) on exfoliated nanosheets of tungsten
      disulfide (WS2) to form plasmonic hotspots. The nanohybrid surface was
      functionalized with specific aptamers which imparted high selectivity for the
      cardiac marker myoglobin (Mb). The fabricated aptasensor was read by SERS using a
      532 nm laser and demonstrated significant signal enhancement, and this allowed Mb
      to be determined in the 10 f. mL-1 to 0.1 MUg mL-1 concentration range. The study
      presents an approach to synergistically exploit the unique chemical and
      electromagnetic properties of both WS2 and AuNPs for many-fold enhancement of
      SERS signals. Graphical abstract Schematic presentation of a nanohybrid-mediated
      SERS substrate prepared by in-situ assembly of gold nanoparticles (AuNPs) reduced
      on exfoliated nanosheets of tungsten disulfide (WS2) to form plasmonic hot spots.
      Specific aptamers immobilized on the SERS surface impart high sensitivity and
      selectivity for the cardiac marker myoglobin (Mb).

PMID- 29594651
TI  - Reading the Bible, Stressful Life Events, and Hope: Assessing an Overlooked
      Coping Resource.
AB  - Many people rely on religion to deal with the stressors in their lives. The
      purpose of this study is to examine a religious coping resource that has received
      relatively little attention-reading the Bible. We evaluated three hypotheses: (1)
      reading the Bible moderates the relationship between stress and hope; (2) people
      who read the Bible more often are more likely to rely on benevolent religious
      reappraisal coping responses; and (3) individuals who rely on benevolent
      religious reappraisals will be more hopeful about the future. Support was found
      for all three hypotheses in our analyses.

PMID- 29594652
TI  - The Relationship Between Religious and Psychospiritual Measures and an
      Inflammation Marker (CRP) in Older Adults Experiencing Life Event Stress.
AB  - Inflammation, often measured by C-reactive protein (CRP), is thought to be
      related to a number of debilitating illnesses as we age, including cardiovascular
      disease, cancer and diabetes. Stress has also been implicated in these processes.
      This study examines potential protective effects of spirituality and religion in
      older adults who have experienced stressful life events. As part of the
      nationwide Landmark Study of Spirituality and Health, a subsample of 643 middle
      aged and older adults (age >= 50) who were at or above the median in number of
      life stressors (>= 2) was included in this analysis. Psychospiritual and
      religious (PS/R) variables included: religious service attendance, prayer,
      religious meaning, religious hope, general meaning, general hope and sense of
      peace. Control variables included: age, gender, education, BMI, smoking, alcohol
      use, social support. Only church attendance predicted significantly lower CRP
      after controlling for covariates, even above the other PS/R variables
      (standardized beta = - 0.14, t = - 3.23 p = 0.001). Those with frequent religious
      service attendance were 38% less likely to have clinically elevated CRP than
      those who attend rarely or never. Religious service attendance may confer
      protection in older adults experiencing stressful events as it was significantly
      associated with lower CRP, an inflammatory marker associated with illness.

PMID- 29594653
TI  - Determination of carbonyl pollutants adsorbed on ambient particulate matter of
      type PM2.5 by using magnetic molecularly imprinted microspheres for sample
      pretreatment and capillary electrophoresis for separation and quantitation.
AB  - The authors describe a method for the determination of carbonyl pollutants
      adsorbed on ambient particulate matter (diameter < 2.5 MUm; PM2.5). 2,4
      Dinitrophenylhydrazine (DNPH) was used to derivatize carbonyl compounds. Magnetic
      molecularly imprinted polymers (MMIPs) selective for 2,4-DNPH were synthesized to
      remove excess of the derivatization reagent 2,4-DNPH. Micellar electrokinetic
      chromatography (MEKC) was then applied to the separation of DNPH-derivatized
      carbonyl compounds. The increased sensitivity of MEKC with UV detection and the
      sample cleanup resulted in drastically reduced sampling times (15 min) with
      detection limits ranging from 0.005-0.068 MUg.m-3 for different carbonyls. The
      method was applied to continuous monitoring of carbonyl compounds on ambient PM
      2.5 for two consecutive months. The concentrations and gas-to-particle ratios of
      carbonyls were determined, and a statistical method was used to evaluate the
      correlation among different carbonyls. It was observed that the total
      concentration of carbonyls, especially of multi-carbon carbonyls, increases with
      the level of air pollution. The level of isovaleraldehyde rises sharply and
      accounts for 37% of total carbonyls on days with extremely humid haze. The ratio
      of acetaldehyde to propionaldehyde (C2/C3) decreases with the duration and
      heaviness of haze conditions. Results indicate that anthropogenic emissions and
      the characteristics of the atmosphere (e.g. temperature, sunlight, and relative
      humidity) are the main factors that lead to abnormally high levels of
      isovaleraldehyde and other carbonyls in ambient PM 2.5. Graphical abstract
      Schematic of a method for the determination of carbonyl pollutants adsorbed on
      ambient fine particle of type PM2.5. Magnetic molecularly imprinted polymers
      (MMIPs) were synthesized to remove the excess derivatization reagent (2,4-DNPH)
      in air sample prior to CE separation.

PMID- 29594654
TI  - Aptamer-based determination of tumor necrosis factor alpha using a screen-printed
      graphite electrode modified with gold hexacyanoferrate.
AB  - An aptamer based method is presented for the voltammetric determination of human
      tumor necrosis factor alpha (TNF-alpha). Layers of gold hexacyanoferrate (AuHCF)
      and gold nanoparticles (AuNPs) were directly immobilized on a graphite screen
      printed electrode (SPE). Through the strong interaction between cyanide ions (CN
      ) of AuHCF and AuNPs, gold nanoparticles are assembled on the modified SPE, and
      this allows for the covalent immobilization of thiolated aptamers against TNF
      alpha (TNF-alpha-Apt). On incubation of the aptasensor with of TNF-alpha, the
      Apt/TNF-alpha complex is formed, and this leads to a hindered electron transfer
      and to a decrease in the peak current of the redox probe. Under optimum
      conditions and at a typical working as low as 0.1 V (vs. a silver pseudo
      electrode), the electrode works in the 10 pg.mL-1 to 40 MUg.mL-1 TNF-alpha
      concentration range, with a 5.5 pg.mL-1 detection limit. The high sensitivity and
      wide detection range of this method allowed TNF-alpha to in human serum be
      detected even at very low concentrations. Graphical abstract Schematic diagram
      for fabrication of aptasensor: (a,b) formation of AuHCF film by
      electrodeposition;

PMID- 29594655
TI  - Uricase based fluorometric determination of uric acid based on the use of
      graphene quantum dot@silver core-shell nanocomposites.
AB  - The authors describe a fluorescent "turn-on" assay for detection of uric acid
      (UA) based on the use of graphene quantum dots coated with a shell of silver
      (GQD@Ag). The fluorescence of the GQDs is quenched by the silver shell. However,
      if the silver shell was removed via etching with H2O2 (which is produced by
      uricase catalyzed oxidation of UA), the fluorescence of the GQDs is restored. The
      resulting increase in fluorescence at 466 nm depends directly on the
      concentration of H2O2, which, in turn, depends on the concentration of UA. The
      method allows UA to be quantitated with a 2 MUM detection limit. It was applied
      to the analysis of human urine samples and exhibited satisfactory results. The
      method is cost-effective, sensitive and selective for UA. In our perception, it
      provides a useful tool in clinical analysis and may be extended to other assays
      based on the use of oxidases. Graphical abstract Schematic of the reduction of
      Ag(I) and the growth of a silver shell on the surface of graphene quantum dots
      (GQDs) to form a GQD@Ag nanocomposite whose fluorescence is quenched. Uricase
      catalyzes the oxidation of uric acid (UA) to produce allantoin and H2O2 which
      etches the silver shell. This results in the release of GQDs and increased
      fluorescence, allowing quantitative analysis of UA.

PMID- 29594656
TI  - Glioblastoma (GBM) effects on quantitative MRI of contralateral normal appearing
      white matter.
AB  - PURPOSE: The objective was to investigate (with quantitative MRI) whether the
      normal appearing white matter (NAWM) of glioblastoma (GBM) patients on the
      contralateral side (cNAWM) was different from NAWM of healthy controls. METHODS:
      Thirteen patients with newly diagnosed GBM and nine healthy age-matched controls
      were MRI-scanned with quantitative magnetization transfer (qMT), chemical
      exchange saturation transfer (CEST), and transverse relaxation time (T2)-mapping.
      MRI scans were performed after surgery and before chemo-radiation treatment.
      Comprehensive qMT, CEST, T2 data were acquired. A two-pool MT model was fit to
      qMT data in transient state, to calculate MT model parameters [Formula: see
      text]. CEST signal was isolated by removing the contributions from the MT and
      direct water saturation, and CEST signal was calculated for Amide (CESTAmide),
      Amine (CESTAmine) and nuclear overhauser effect, NOE (CESTNOE). RESULTS: There
      was no difference between GBM patients and normal controls in the qMT properties
      of the macromolecular pool [Formula: see text]. However, their free water pool
      spectrum was different (1/RaT2a,patient = 28.1 +/- 3.9, 1/RaT2a,control = 25.0 +/
      1.1, p = 0.03). This difference could be attributed to the difference in their
      T2 time ([Formula: see text] = 83 +/- 4, [Formula: see text] = 88 +/- 1, p =
      0.004). CEST signals were statistically significantly different with the
      CESTAmide having the largest difference between the two cohorts
      (CESTAmide,patient = 2.8 +/- 0.4, CESTAmide,control = 3.4 +/- 0.5, p = 0.009).
      CONCLUSIONS: CEST in cNAWM of GBM patients was lower than healthy controls which
      could be caused by modified brain metabolism due to tumor cell infiltration.
      There was no difference in MT properties of the patients and controls, however,
      the differences in free water pool properties were mainly due to reduced T2 in
      cNAWM of the patients (resulting from structural changes and increased
      cellularity).

PMID- 29594657
TI  - A predictive value of von Willebrand factor for early response to Bevacizumab
      therapy in recurrent glioma.
AB  - Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular
      endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent
      with antitumor activity. The aim of this single-center, retrospective,
      longitudinal study was to investigate the possible predictive value of baseline
      demographic, clinical and laboratory parameters for early 3-month response to BV
      therapy in patients with recurrent glioma. Forty-nine patients with recurrent
      glioma received BV at 10 mg/kg intravenously every 3 weeks alone or in
      association with chemotherapy were included in this study. Blood samples were
      collected from all patients before the first (baseline), the second and the third
      administration of BV. After 3 months of BV therapy, patients with partial
      response were defined as responders whereas patients with stable or progressive
      disease were defined as non-responders. The median overall follow-up was 8 months
      (range 1-73), the median overall survival (OS) was 8 months (95% CI 6-10) and the
      median progression free survival (PFS) was 4 months (95% CI 3-5). Thirty-five %
      of patients were responders and showed significantly lower von Willebrand factor
      (VWF) levels than non-responders at all sample times (p < .02 for all). Also, on
      multivariate analysis the baseline VWF value was the only predictor for an early
      response to BV therapy. Furthermore, D-dimer and prothrombin fragment 1+2 were
      predictive factors for OS while Karnofsky performance status resulted predictive
      for PFS. VWF antigen value is a possible predictive biomarker for an early 3
      month response to BV therapy in recurrent glioma.

PMID- 29594658
TI  - A glassy carbon electrode modified with poly(2,4-dinitrophenylhydrazine) for
      simultaneous detection of dihydroxybenzene isomers.
AB  - 2,4-Dinitrophenylhydrazine (DNPH) was electropolymerized on the surface of an
      anodized glassy carbon electrode by cyclic voltammetry. The anodized electrode
      has a highly electroactive surface due to the creation of chemically
      functionalized graphitic nanoparticles, and this facilitates the formation of
      poly-DNPH via radical polymerization. Poly-DNPH displays excellent redox activity
      due to the presence of nitro groups on its backbone. These catalyze the electro
      oxidation of hydroquinone (HQ) and catechol (CT). The peak-to-peak separation is
      around 109 mV, while a bare GCE cannot resolve the peaks (located at 165 and 274
      mV vs. Ag/AgCl). Sensitivity is also enhanced to ~1.20 and 1.19 MUA.cm-2.MUM-1,
      respectively. The sensor has a linear response that covers the 20-250 MUM
      concentration range for both HQ and CT, with 0.75 and 0.76 MUM detection limits,
      respectively, at simultaneous detection. Commonly present species do not
      interfere. Graphical abstract A novel conducting poly(2,4-dinitrophenylhydrazine)
      modified anodized glassy carbon electrode (pDNPH/AGCE) was developed by
      electrochemical method. The electro-catalytic activity of pDNPH/AGCE sensor was
      investigated for the selective and simultaneous electrochemical detection of
      hydroquinone (HQ) and catechol (CT), which revealed high sensitivities and low
      detection limits with excellent stability.

PMID- 29594659
TI  - Involvement and Influence of Healthcare Providers, Family Members, and Other
      Mutation Carriers in the Cancer Risk Management Decision-Making Process of BRCA1
      and BRCA2 Mutation Carriers.
AB  - Deciding between increased cancer screening or prophylactic surgery and the
      timing of such procedures can be a difficult and complex process for women with
      BRCA mutations. There are gaps in our understanding of involvement of others in
      the decision-making process for women with BRCA mutations. This study evaluated
      the management decision-making process of women with BRCA mutations, focusing on
      the involvement of others. Grounded theory was used to analyze and code risk
      management decision-making information from interviews with 20 BRCA mutation
      carriers. Unaffected at-risk participants with a BRCA mutation, those under age
      40, and those with no children described having a difficult time making risk
      management decisions. Physicians were an integral part of the decision-making
      process by providing decisional support and management recommendations. Family
      members and other mutation carriers filled similar yet distinct roles by
      providing experiential information as well as decisional and emotional support
      for carriers. Participants described genetic counselors as short-term providers
      of risk information and management recommendations. The study findings suggest
      that unaffected at-risk women, women under 40, and those who do not have children
      may benefit from additional support and information during the decision-making
      process. Genetic counselors are well trained to help women through this process
      and connect them with resources, and may be under-utilized in long-term follow-up
      for women with a BRCA mutation.

PMID- 29594660
TI  - Macroemulsion-based dispersive magnetic solid phase extraction for
      preconcentration and determination of copper(II) in gasoline.
AB  - A new method referred to as microemulsion-based Dispersive Magnetic Solid-Phase
      Extraction (MDM-SPE) is presented for use in the extraction and preconcentration
      of metal ions from complex organic matrices. MDM-SPE combines the features of
      magnetic nanoparticles (MNPs) and microemulsions. It was successfully applied to
      the extraction of copper(II) from gasoline prior to its determination by Graphite
      Furnace Atomic Absorption Spectrometry (GF-AAS). The material for use in MDM-SPE
      was obtained by first functionalizing MNPs of the type Fe3O4@Al2O3 with sodium
      dodecyl sulfate and the chelator 1-(2-pyridylazo)-2-naphthol (PAN) dispersed in 1
      propanol. The resulting functionalized magnetic MNPs were dispersed in a
      microemulsion prepared from gasoline, buffer, and 1-propanol. After waiting for 5
      s (during which the formation of the copper complex on the MNPs is complete), the
      MNPs are magnetically separated. The complex was then eluted with 2 mol L-1 HNO3,
      and the eluate submitted to GF-AAS. Various parameters were optimized. Copper(II)
      can be quantified by this method over a linear range that extends from 2.0 to
      10.0 MUg.L-1. Other figures of merit include (a) a 37 ng.L-1 detection limit, (b)
      a repeatability of 1.1%, (c) a reproducibility of 2.1%, and (d) an enrichment
      factor of nine. The high surface-to-volume ratio of the microemulsion containing
      the dispersed magnetic sorbent warrants an efficient contact for reaction between
      copper(II) and the complexing agent, and this results in fast (about 40 s)
      extraction and pre-concentration of copper(II). MDM-SPE is accurate, precise and
      efficient. Microemulsions do not break down, and phase separation, heating,
      laborious, and time-consuming sample preparation, and incorporation of impurities
      into the graphite furnace (which can generate inaccuracies in GF-AAS analysis)
      are not needed. Graphical abstract Schematic of a new method for Microemulsion
      based Dispersive Magnetic Solid-Phase Extraction (MDMSPE) using functionalized
      magnetic nanoparticles (FMNPs). It was applied to the preconcentration of
      copper(II) in gasoline.

PMID- 29594661
TI  - Advances in the use of carbonaceous materials for the electrochemical
      determination of persistent organic pollutants. A review.
AB  - Persistent organic pollutants (POPs) are key pollutants due to their persistence,
      refractory biodegradation, high toxicity and bioaccumulation in the food chain.
      This review (with 93 refs.) covers the progress made in the past decades in the
      application of carbonaceous materials for electrochemical detection of POPs as
      listed in the Stockholm Convention. Following an introduction into the field,
      typical carbonaceous materials for use in electrodes are discussed, with
      subsection on carbon nanotubes, graphene, reduced graphene oxide, graphitic
      carbon nitride and carbon dots. This is followed by a section on application of
      carbonaceous materials in electrochemical detection, with subsections on the use
      of carbon nanotubes, of (doped-) graphene, of reduced graphene oxide, of
      graphitic carbon nitride, and of carbon dots. The review concludes with
      conclusions and future perspectives. The detection mechanisms of POPs are also
      discussed. Graphical abstract Advanced carbonaceous materials for the
      electrochemical determination of persistent organic pollutants.

PMID- 29594662
TI  - Bare eye detection of Hg(II) ions based on enzyme inhibition and using
      mercaptoethanol as a reagent to improve selectivity.
AB  - The authors describe a colorimetric method for the determination of Hg2+ ions
      based on the inhibition of the activity of the enzyme urease. The pH value of
      solution increases when urease hydrolyzes urea, which can be visualized by adding
      a pH indicator such as Phenol Red (PhR). Mercaptoethanol as a typical thiol is
      added to the system to improve selectivity because it binds metal ions and then -
      unlike the Hg2+ mercaptoethanol complex - does not inhibit urease. Hence, the
      color of the pH indicator PhR turns from yellow to pink as the solution becomes
      alkaline. The Hg2+ mercaptoethanol complex, in contrast, strongly inhibits urease
      and the color of the solution remains yellow. The findings were used to design a
      photometric assay based on the measurement of the ratio of absorptions of PhR at
      558 nm and 430 nm. It has a linear response over the 25 to 40 nM Hg2+
      concentration range and a 5 nM detection limit. This is well below the guideline
      values of Hg2+ specified by the US Environmental Protection Agency and the World
      Health Organization for drinking water (10 nM and 30 nM, respectively). The
      method was employed to the determination of Hg2+ in water samples spiked with 10
      nM levels of Hg2+ where color changes still can be observed visually. Graphical
      Abstract Schematic presentation of a colorimetric method for the ultrasensitive
      detection of Hg2+ based on the inhibition of urease activity. Mercaptoethanol is
      used to improve the selectivity. Even at Hg2+ concentrations as low as 5 nM, the
      color change still can be easily observed by bare eyes.

PMID- 29594663
TI  - A composite consisting of microporous carbon and cobalt(III) oxide and prepared
      from zeolitic imidazolate framework-67 for voltammetric determination of ascorbic
      acid.
AB  - A nanoporous carbon/cobalt oxide (NPC/Co3O4) composite was synthesized from a
      single-precursor (zeolitic imidazolate framework-67). Transmission electron
      microscopy showed that the Co3O4 nanoparticles with an average particle size of
      10 nm (+/-2 nm) were well dispersed in the NPC matrix. However, in a few places,
      Co3O4 nanoparticles were aggregated. The composite shows outstanding performance
      in terms of electrooxidation of ascorbic acid (AA) in phosphate buffer of pH 7.0.
      The differential pulse voltammetric response of the composite electrode (at 0.12
      V vs. SCE) is linear in the 2-240 MUM AA concentration range, with a 20 nM
      detection limit. The electrode exhibits high sensitivity (0.13 MUA.MUM.cm-2),
      reliable reproducibility, and good selectivity. The method, when applied to the
      direct determination of AA in vitamin C tablets, gave recoveries between 98.0 and
      102.0%. Graphical abstract A nanoporous carbon composite decorated with Co2O3
      nanoparticles was prepared from a single precursor (the zeolitic imidazolate
      framework-67). It shows outstanding performance in terms of electrooxidation of
      ascorbic acid with high sensitivity (0.13 MUA.MUM.cm-2), reliable
      reproducibility, and good selectivity.

PMID- 29594664
TI  - Selective extraction of theophylline from plasma by copper-doped magnetic
      microspheres prior to its quantification by HPLC.
AB  - The authors describe the preparation of copper-doped magnetic microspheres (Cu
      Fe3O4) by a solvothermal method. Due to their good magnetic property and high
      affinity for compounds containing an imidazole moiety (containing N-H), they are
      excellent adsorbents for such compounds as tested by eighteen compounds.
      Specifically, a method has been developed for magnetic solid-phase extraction
      (MSPE) of theophylline (TP) from plasma. The method enables selective enrichment
      of TP over many potential interferents that can occur in plasma. Following
      elution with alkaline methanol, TP was quantified by HPLC-UV at a detection
      wavelength of 272 nm. Under the optimized conditions, a linear response is found
      for the 0.02 to 20 MUg.mL-1 concentration range, and the limit of detection is as
      low as 3 ng.mL-1. Recoveries from spiked samples range from 91.2 to 100.4%, and
      the repeatabilities are between 2.9 and 12% (for n = 6). The method was
      successfully applied to the determination of TP in rabbit and rat plasma.
      Graphical abstract Copper-doped magnetic microspheres are described that show
      good magnetic property and high affinity for compounds containing an imidazole
      moiety (containing an N-H group). They were successfully applied to the selective
      extraction of theophylline in plasma.

PMID- 29594665
TI  - Gold nanoparticle based photometric determination of tobramycin by using new
      specific DNA aptamers.
AB  - A magnetic bead-based SELEX was applied to identify 37 single-stranded DNA
      aptamers specific for tobramycin after ten rounds of selection. The aptamers were
      classified into nine families according to sequence analysis. Among them, several
      aptamers with typical sequences were selected and their dissociation constants
      (Kds) were determined by a fluorescent method. An aptamer termed "Ap 32", with a
      Kd value of 56.8 +/- 4.6 nM, possesses the highest affinity and satisfactory
      specificity. Theoretical modeling showed that nucleotides 14-18 and 26-29 play a
      most significant role in the interaction between aptamer and tobramycin.
      Subsequently, the sequence of Ap 32 was optimized through rationally designed
      truncation. The truncated aptamer Ap 32-2 consists of 34 nucleotides and has a Kd
      that is similar to the original one. It was chosen as the optimal aptamer for use
      in the assay and was immobilized on gold nanoparticles. On addition of
      tobramycin, the color turns from red to purple. The findings were used to design
      a photometric assay (best performed at 520 nm) that has a linear response in the
      100 nM to 1.4 MUM concentration range, with a 37.9 nM detection limit. The method
      was successfully applied to the determination of tobramycin in (spiked) honey
      samples. Graphical abstract A 34-nucleotide aptamer specific for tobramycin was
      obtained through magnetic beads-based systematic evolution of ligands by
      exponential enrichment (SELEX) and structural analysis-based rational post-SELEX
      truncation, and then applied to the determination of tobramycin using a gold
      nanoparticle-based photometric assay.

PMID- 29594666
TI  - A polydopamine-based molecularly imprinted polymer on nanoparticles of type
      SiO2@rGO@Ag for the detection of lambda-cyhalothrin via SERS.
AB  - A new method is described for the determination of the pesticide lambda
      cyhalothrin (LC). It combines SERS detection with molecular imprinting and
      largely improves selectivity. A multilayer surface imprinted nanocomposite was
      synthesized in two steps on a nanostructure of type SiO2@rGO@Ag acting as a
      substrates. Firstly, the surface of the SiO2@rGO@Ag composite was modified with
      self-polymerized dopamine. Secondly, surface-initiated polymerization was carried
      out to prepare a molecularly imprinted polymer (MIP) using LC as the template.
      The use of this SiO2@rGO@Ag-MIP allows for excellent SERS based detection and has
      high selectivity for LC. The Raman intensity and LC concentration present perfect
      linear relationship between 10-5 to 10-9 mol L-1 and the detection limit is
      3.8*10-10 mol L-1. All the procedures are conducted in aqueous or ethanol
      solution. Graphical abstract Schematic of a new method for determination of the
      pesticide lambda-cyhalothrin. It combines SERS detection with molecular
      imprinting and largely improves selectivity. A multilayer surface imprinted
      nanocomposite was synthesized in two steps on a nanostructure of type SiO2@rGO@Ag
      acting as a substrates.

PMID- 29594667
TI  - Magnetic nanoparticles coated with a molecularly imprinted polymer doped with
      manganese-doped ZnS quantum dots for the determination of 2,4,6-trichlorophenol.
AB  - The authors describe a multifunctional magnetic molecularly imprinted
      phosphorescent nanoparticle probe for the selective determination of 2,4,6
      trichlorophenol (2,4,6-TCP). The probe consists of a magnetite (Fe3O4) core that
      is coated with a molecularly imprinted polymer doped with Mn-doped ZnS quantum
      dots (QDs). The MIP was obtained by copolymerization of acrylamide, ethylene
      glycol dimethacrylate, and 2,4,6-TCP. The resulting nanoprobe shows strong
      phosphorescence (with excitation/emission peaks at 320/594 nm) due to the
      presence of the QDs, good magnetism, and high selectivity for 2,4,6-TCP. Under
      optimal detection condition, response is linear in the 0.1-30 MUmol L-1 2,4,6-TCP
      concentration range. The imprinting factor is 8.84, and the detection limit is 35
      nmol L-1. The method was successfully applied to the determination of 2,4,6-TCP
      in spiked river water and waste water. Graphical abstract Schematic of a
      multifunctional phosphorescent probe for 2,4,6-trichlorophenol. It consists of a
      magnetic core coated with a molecularly imprinted polymer shell containing Mn(II)
      doped ZnS quantum dots whose room-temperature phosphorescence is quenched by
      2,4,6-trichlorophenol.

PMID- 29594668
TI  - Synthesis of Er(III)/Yb(III)-doped BiF3 upconversion nanoparticles for use in
      optical thermometry.
AB  - The authors describe an ethylene glycol assisted precipitation method for
      synthesis of Er(III)/Yb(III)-doped BiF3 nanoparticles (NPs) at room temperature.
      Under 980-nm light irradiation, the NPs emit upconversion (UC) emission of
      Er(III) ions as a result of a two-photon absorption process. The temperature
      dependent green emissions (peaking at 525 and 545 nm) are used to establish an
      unambiguous relationship between the ratio of fluorescence intensities and
      temperature. The NPs have a maximum sensitivity of 6.5 * 10-3 K-1 at 619 K and
      can be applied over the 291-691 K temperature range. The results indicate that
      these NPs are a promising candidate for optical thermometry. Graphical abstract
      Schematic of the room-temperature preparation of Er(III)/Yb(III)-doped BiF3
      nanoparticles with strongly temperature-dependent upconversion emission.

PMID- 29594669
TI  - DNA nanosensors based on the use of single gold nanowire electrodes and Methylene
      Blue as an intercalator.
AB  - The authors describe an electrochemical DNA nanosensor based on the use of single
      gold nanowire electrodes (AuNWEs). The probe DNA is immobilized on the AuNWE via
      Au-S bonds that are formed between thiol-terminated DNA and the gold surface.
      Single AuNWEs were prepared by an improved laser-assisted pulling method and
      hydrofluoric acid etching. The nanoelectrodes were characterized by cyclic
      voltammetry and COMSOL simulation. Square wave voltammetry was used to monitor
      the DNA hybridization event between probe DNA and target DNA by using Methylene
      Blue (MB) as an intercalator of dsDNA. Under optimal conditions, the peak current
      for MB (best measured at a potential of -0.2 V vs. Ag/AgCl) increases linearly
      with the logarithm of the analyte concentration in the 1.0 f. to 10 nM range,
      with a 0.48 fmM detection limit at an S/N ratio of 3. The assay is highly
      selective, reproducible and stable. Considering the small overall dimensions and
      high sensitivity, this nanoelectrode potentially can be applied to in-vivo
      sensing of DNA inside living cells Graphical abstract Schematic presentation of
      an electrochemical DNA nanosensor using single gold nanowire electrodes and based
      on the interaction of thiol-terminated DNA and gold surface. It was used to
      detect complementary DNA with high selectivity and sensitivity.

PMID- 29594670
TI  - The Quest for Clarity in Research Integrity: A Conceptual Schema.
AB  - Researchers often refer to "research integrity", "scientific integrity",
      "research misconduct", "scientific misconduct" and "research ethics". However,
      they may use some of these terms interchangeably despite conceptual distinctions.
      The aim of this paper is to clarify what is signified by several key terms
      related to research integrity, and to suggest clearer conceptual delineation
      between them. To accomplish this task, it provides a conceptual analysis based
      upon definitions and general usage of these phrases and categorization of
      integrity-breaching behaviours in literature and guidelines, including
      clarification of the different domains and agents involved. In the first part of
      the analysis, following some initial clarifications, I explore the distinction
      between internal and external rules of integrity. In the second part, I explore
      the distinction between integrity and lack of misconduct, before suggesting a
      recategorisation of different types of integrity breach. I conclude that greater
      clarity is needed in the debate on research integrity. Distinguishing between
      scientific and research integrity, reassessing the relative gravity of different
      misbehaviours in light of this distinction, and recognising all intentional
      breaches of integrity as misconduct may help to improve guidelines and education.

PMID- 29594671
TI  - Demonstration of the lack of cytotoxicity of unmodified and folic acid modified
      graphene oxide quantum dots, and their application to fluorescence lifetime
      imaging of HaCaT cells.
AB  - The authors describe the synthesis of water-soluble and fluorescent graphene
      oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant
      graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic
      acid receptors are overexpressed in cancer cells and hence can bind to
      functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs
      display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs
      are non-toxic to macrophage cells even after prolonged exposure and high
      concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used
      (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior
      method for bioimaging. Graphical abstract Schematic representation of graphene
      oxide quantum dots, folic acid modified graphene oxide quantum dots (red), and
      the use of fluorescence lifetime to discriminate against green auto-fluorescence
      of HeCaT cells.

PMID- 29594672
TI  - Hyaluronic acid functionalized nanostructured sensing interface for voltammetric
      determination of microRNA in biological media with ultra-high sensitivity and
      ultra-low fouling.
AB  - An electrochemical biosensor for the detection of microRNA was prepared via
      chemical grafting of a Methylene Blue labeled reporter (MB-Rep) duplex onto a
      nanostructured surface that was obtained by electrodeposition of cobalt oxide and
      poly(o-phenylenediamine). This is followed by the attachment of hyaluronic acid
      and gold nanoclusters. In the presence of the target (microRNA), the probe-target
      duplex and the MB-Rep hairpin are formed. These will displace the labeled
      reporter from the sensor surface, and this results in a decrease of the
      amperometric signal for MB at a typical working voltage of -0.28 V (vs. Ag/AgCl).
      The electrode modified with hyaluronic acid possesses a large electroactive
      surface area and an excellent antifouling property. This makes it useful for
      ultrasensitive quantitation of microRNA even in complex biological media. The
      sensor has a linear response in the 100 f. to 0.1 MUM microRNA concentration
      range, and a 33.3 f. detection limit. It was successfully applied to the
      determination of microRNA in cancer cells. Graphical abstract ?.

PMID- 29594673
TI  - Colorimetric detection of Hg(II) by measurement the color alterations from the
      "before" and "after" RGB images of etched triangular silver nanoplates.
AB  - It is shown that triangular silver nanoplates (TAgNPs) are viable colorimetric
      probes for the fast, sensitive and selective detection of Hg(II). Detection is
      accomplished by reducing Hg(II) ions to elemental Hg so that an Ag/Hg amalgam is
      formed on the surface of the TAgNPs. This leads to the inhibition of the etching
      TAgNPs by chloride ions. Correspondingly, a distinct color transition can be
      observed that goes from yellow to brown, purple, and blue. The color alterations
      extracted from the red, green, and blue part of digital (RGB) images can be
      applied to the determination of Hg(II). The relationship between the Euclidean
      distances (EDs), i.e. the square roots of the sums of the squares of the DeltaRGB
      values, vary in the 5 nM to 100 nM Hg(II) concentration range, and the limit of
      detection is as low as 0.35 nM. The color changes also allow for a visual
      estimation of the concentrations of Hg(II). The method is simple in that it only
      requires a digital camera for data acquisition and a Photoshop software for
      extracting RGB variations and data processing. Graphical abstract Hg2+ detection
      was achieved by anti-etching of TAgNPs caused by the formation of silver amalgam,
      along with vivid multicolor variations from yellow to brown, purple, and
      eventually to be blue.

PMID- 29594674
TI  - Child Art Psychotherapy in CAMHS in Ireland-a parent satisfaction study.
AB  - OBJECTIVES: We aimed to evaluate parent satisfaction with the Vasarhelyi method
      of Child Art Psychotherapy offered at two Child and Adolescent Mental Health
      teams by postal survey using the Client Satisfaction Questionnaire, and by
      performing a qualitative interview. METHODS: Parents of 29 children who attended
      Child Art Psychotherapy over the previous 4 years were invited to participate
      they were sent the Client Satisfaction Questionnaire and invited to attend for an
      interview about Child Art Psychotherapy. The postal survey was followed up by a
      telephone call to complete missing surveys. The Client Satisfaction Questionnaire
      has a 4-point Likert scale with a minimum score of 8 and maximum score (highest
      satisfaction) of 32. RESULTS: Fourteen Client Satisfaction questionnaires were
      returned indicating a response rate of 48%. The mean age of the children who
      attended CAP was 10.84 years. The mean CSQ-8 score was 25.6 (95% CI 22.0-29.3)
      with a range of 8 to 32. Eighty-five percent of parents indicated that they were
      satisfied on all questions regarding the service of CAP their child received. One
      of 29 parents attended for interview and 4 themes were identified in the
      interview: (1) the importance of the child's opinion, (2) behavioural change
      occurred during and after CAP, (3) the parent would recommend CAP to others, and
      (4) parental expectations of therapy and level of engagement. CONCLUSION: Parents
      are satisfied with the Vasarhelyi method of Child Art Psychotherapy.

PMID- 29594675
TI  - The mechanism of the adsorption of dsDNA on citrate-stabilized gold nanoparticles
      and a colorimetric and visual method for detecting the V600E point mutation of
      the BRAF gene.
AB  - A study is presented on the binding kinetics and mechanism of the adsorption of
      dsDNA on citrate-capped gold nanoparticles (AuNPs). Methods include fluorescence
      titration, isothermal calorimetry (ITC) titration, dynamic light scattering and
      gel electrophoresis. It is found that the fluorescence of probe DNA (labeled with
      Rhodamine Green and measured at excitation/emission peaks of 498/531 nm) is
      quenched by addition of AuNPs. The Stern-Volmer quenching constant (Ksv) is 1.67
      * 10^9 L.mol-1 at 308 K and drops with increasing temperature. The quenching
      mechanism is mainly static. The results of both fluorescence titrations and ITC
      show negative values for DeltaH and DeltaS values. This shows ion-induced dipole
      dipole interaction to be the main attractive forces between dsDNA and AuNPs,
      while electrostatic interactions result in repulsion. The repulsive forces lead
      to a lower affinity between dsDNA and AuNPs (compared to single-strand DNA). It
      is also found that dsDNA can prevent the aggregation of AuNPs which is
      accompanied by a color change from red into blue. The visual detection limit with
      bare eyes for dsDNA1 is 36 pM. Based on these findings, a colorimetric method was
      developed to detect the proto-oncogene of serine/threonine-protein kinase B-Raf
      V600E point mutation in HT29, Ec109, A549, Huh-7 and SW480 cell lines. Graphical
      abstract Schematic of the salt-induced aggregation of uncapped gold nanoparticles
      (AuNPs) which leads to a color change from red to blue. If the AuNPs are coated
      with dsDNA, aggregation is suppressed.

PMID- 29594676
TI  - Patient and health professional satisfaction with an interdisciplinary patient
      safety program.
AB  - Background Measuring humanistic outcomes is an important component of valuating
      healthcare services. There is a paucity of data on satisfaction with pharmacist
      implemented clinical services in long-term care settings. Objective To evaluate
      patient and health professional (HP) satisfaction with an interdisciplinary
      patient safety program performed in elderly patients with polypharmacy admitted
      to a long-term care hospital (LTCH). Method An interventional, longitudinal,
      prospective study was conducted in a Spanish LTCH. Pharmacist conducted the
      pharmacotherapy follow-up (reconciliation, pharmacotherapeutic optimization and
      educational interviews). Two satisfaction surveys were designed on a 10-point
      Likert-type scale. The patient survey was administered at discharge. The HP
      survey included the following dimensions: knowledge and program importance,
      pharmacist skills and pharmacist contributions to the interdisciplinary team. A
      reliability analysis was performed. Results 123 surveys were completed and
      returned; 74 patient surveys (response rate 97.4%) and 49 HP surveys (response
      rate 98.0%). The overall mean score of the patient survey was 9.46 +/- 0.87,
      resulting in 82.4% very satisfied and 17.6% satisfied. The overall mean score of
      the HP survey was 8.85 +/- 1.42, resulting in 65.3% very satisfied and 30.6%
      satisfied. Conclusion Elderly patients with polypharmacy and HPs reported high
      levels of satisfaction with the interdisciplinary patient safety program
      implemented in an LTCH. This positive response supports the value of pharmacists
      for managing older high-risk populations.

PMID- 29594677
TI  - Monitoring of gentamicin serum concentrations in obstetrics and gynaecology
      patients in Namibia.
AB  - Background Therapeutic drug monitoring is frequently used to optimize the
      gentamicin dose. Objective The study investigated whether a 240 mg once daily
      standard dose achieves the recommended target serum gentamicin concentrations.
      Setting The prospective, observational study took place in the 2 major public
      hospitals in Namibia. Method Twenty-nine female patients receiving a standard
      dose (240 mg gentamicin once daily) participated in the study. Two blood samples
      were withdrawn to estimate gentamicin pharmacokinetic parameters. Serum
      creatinine was used to calculate creatinine clearance with the Cockcroft-Gault
      formula (CLcr), and estimate glomerular filtration rate (eGFR) by the Modified
      Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equations. Main outcome measure The outcome measure was
      the proportion of patients receiving 240 mg gentamicin once daily having Cmax
      values above 15 mg/L. Results Total body weight (TBW) and body mass index were
      highly variable: 43-115 kg, and 17.3-41.3 kg/m2, respectively. The gentamicin
      dose normalized for TBW (adjusted body weight for obese patients) was relatively
      low, i.e. 4.2 +/- 0.8 mg/kg (mean SD). Gentamicin Cmax was 14.4 +/- 4.7 mg/L;
      only 9 patients (31%) had a Cmax > 15 g/mL. eGFR (MDRD-4) correlated well with
      CLcr, but eGFR (EPI-CKD) formula showed systematic deviations from CLcr.
      Conclusions (1) a standard 240 mg dose results in gentamicin Cmax values below 15
      mg/L in the majority of the patients, (2) eGFR formulas to estimate kidney
      function will have to be evaluated for their usefulness in the Namibian patient
      population.

PMID- 29594678
TI  - Aptamer based fluorometric beta-lactoglobulin assay based on the use of magnetic
      nanoparticles and carbon dots.
AB  - The authors describe a fluorometric aptamer based assay for detecting beta
      lactoglobulin by using carbon dots (C-dots) as a signal indicator. The aptamer
      was immoblized on magnetite (Fe3O4) nanoparticles (MNPs), and the C-dots served
      as a label for the complementary oligonucleotide (cDNA). The assay is based on
      the hybridization that takes place between aptamer and cDNA. In the presence of
      beta-lactoglobulin (beta-LG), the aptamer preferentially binds to beta-LG, and
      this leads to a partial release of the C-dots-cDNA into the solution. After
      magnetic separation, the supernatant of the solution contains the released C-dots
      cDNA which are quantified by fluorometry, best under excitation/emission
      wavelengths of 354/447 nm. Under the optimal conditions, the fluorescence
      intensity is proportional to the logarithm of the beta-LG concentration in the
      0.25 to 50 ng mL-1 range, with a 37 pg mL-1 detection limit. The method was
      successfully applied to the determination of beta-LG in hypoallergenic
      formulations, and the results demonstrated that this assay is a promising tool in
      food quality control. Conceivably, it also provides the opportunity for detection
      of other analytes. Graphical abstract Schematic of a novel aptamer based
      fluorometric beta-lactoglobulin assay based on the use of magnetite (Fe3O4)
      nanoparticles (MNPs) and carbon dots (C-dots). C-dots were used as a signal
      indicator and Fe3O4 MNPs acted as a magnetic separator. This assay exhibits high
      sensitivity and selectivity with a detection limit as low as 37 pg mL-1.

PMID- 29594679
TI  - Ion beam sputtering deposition of silver nanoparticles and TiOx/ZnO
      nanocomposites for use in surface enhanced vibrational spectroscopy (SERS and
      SEIRAS).
AB  - Hybrids consisting of silver nanoparticles (in varying fractions) and of TiOx/ZnO
      were prepared via top-down ion beam sputtering (IBS) deposition on silicon
      substrates. The deposited nanomaterials were characterized by scanning electron
      microscopy and X-ray photoelectron spectroscopy. It is shown that such composites
      represent a viable substrate for use in both surface enhanced Raman spectroscopy
      (SERS) and surface enhanced infrared absorption spectroscopy (SEIRAS), as
      exemplarily shown for crystal violet as the model analyte. The C-H bending mode
      at about 1181 cm-1 and the C-N vibration at 1361 cm-1 observed in the SERS and
      SEIRAS spectra, respectively, have been used as analytical signal. The substrate
      consisting of TiOx NPs with 33% fraction of silver provides the strongest
      enhancement in SERS (up to 10,000-fold), while TiOx/AgNPs with thickness of 2 and
      1 nm in ion beam sputtering, respectively, provides the best sensitivity in
      SEIRAS. The substrates also display photocatalytic activity as shown by the
      degradation of adsorbed crystal violet under ultraviolet irradiation. Graphical
      abstract Schematic of the preparation of hybrid substrates consisting of Ag and
      TiOx/ZnO nanoparticles via ion beam sputtering deposition. They were applied in
      both surface enhanced Raman and surface enhanced infrared absorption
      spectroscopies using crystal violet as model analyte, showing enhancements up to
      >10,000-fold in Raman.

PMID- 29594680
TI  - Determination of vanillin by using gold nanoparticle-modified screen-printed
      carbon electrode modified with graphene quantum dots and Nafion.
AB  - A voltammetric analytical assay for the selective quantification of vanillin is
      described. It is based on the use of a gold nanoparticle-modified screen-printed
      carbon electrode (SPCE) modified with graphene quantum dots (GQD) in a Nafion
      matrix. The GQD were synthesized by an acidic thermal method and characterized by
      UV-Vis, photoluminescence, and FTIR spectroscopy. The modified SPCE displays a
      strongly enhanced response to vanillin. Linear sweep voltammetry (LSV) and
      differential pulse voltammetry (DPV) were applied to optimize the methods. The
      analytical assay has linear responses in the 13 to 660 MUM and 0.66 to 33 MUM
      vanillin concentration ranges. The detection limits are 3.9 MUM and 0.32 MUM when
      using LSV and DPV, respectively. The analytical assay is selective and stable. It
      was applied to the determination of vanillin in several food samples with
      satisfactory results. Recoveries from spiked samples ranged between 92.1 and
      113.0%. Graphical abstract The selective and sensitive quantification of vanillin
      is carried out by the use of a gold nanoparticle-modified screen-printed carbon
      electrode modified with graphene quantum dots in a Nafion matrix.

PMID- 29594681
TI  - Reusable resistive aptasensor for Pb(II) based on the Pb(II)-induced
      despiralization of a DNA duplex and formation of a G-quadruplex.
AB  - The article describes a reusable biosensor for Pb(II) ions. A duplex DNA with a
      terminal amino group and containing a G-quadruplex (G4) aptamer was covalently
      conjugated to single walled carbon nanotubes on a field effect transistor (FET).
      The detection scheme is based on the despiralization of the DNA duplex because
      Pb(II) can induce the G4 aptamer to form a stabilizing G4/Pb(II) complex. This
      structural change affects the electrical conductivity of SWNTs which serves as
      the analytical signal. The biosensor was characterized via scanning electron
      microscopy, Raman, UV-vis, and voltage-current profiles. Under optimized
      conditions, the relative resistance at 0.02 V increases linearly with the
      logarithm of the Pb(II) concentration in the range from 1 ng.L-1 to 100 MUg.L-1,
      and the limit of detection is 0.39 ng.L-1. Compared to other sensors, this oner
      demonstrates superior simplicity, sensitivity, and selectivity even in mixtures
      of heavy metal ions. It was applied to the determination of Pb(II) in (spiked)
      water and soil samples and gave good results. Graphical abstract Schematic of the
      fabrication a biosensor for Pb(II). It is making use of an SWNT-based FET, G4-DNA
      and complementary DNA with an amino group. Pb(II) can despiralize the DNA duplex
      to form a G-quadruplex which affects the electrical conductivity of SWNTs. After
      each detection, the single complementary strand DNA can rebind the G4-DNA, which
      makes the biosensor reusable.

PMID- 29594682
TI  - A glassy carbon electrode modified with N-doped carbon dots for improved
      detection of hydrogen peroxide and paracetamol.
AB  - Nitrogen doped carbon dots (NCDs) were synthesized using a low temperature
      approach and used to modify a glassy carbon electrode (GCE) via dipping. The
      oxygen groups on the surface of the NCDs, and the charge delocalization of the
      NCDs warrant an excellent electrocatalytic activity of the GCE toward oxidation
      of paracetamol (PA) and reduction of H2O2. PA and H2O2 were detected at 0.34 V
      and -0.4 V (both vs. Ag/AgCl) using differential pulse voltammetry and
      amperometric I-T measurement, respectively. The modified GCE has a linear
      response to PA in the 0.5 to 600 MUM concentration range, and to H2O2 in the 0.05
      MUM to 2.25 mM concentration range. The detection limits are 157 nM and 41 nM,
      respectively. In our perception, the modified GCE holds promise for stable,
      selective and sensitive determination of PA and H2O2 in pharmaceutical analysis.
      Graphic abstract Nitrogen doped carbon dots (NCDs) were synthesized and used to
      modify a glassy carbon electrode. Surface functional groups on NCDs can trigger
      electrocatalytic reactions toward paracetamol oxidation and H2O2 reduction with
      high sensitivities.

PMID- 29594683
TI  - Visual and colorimetric determination of H2O2 and glucose based on citrate
      promoted H2O2 sculpturing of silver nanoparticles.
AB  - Isotropic silver nanoparticles (iAg NPs) can be easily prepared at low costs,
      have a low electrochemical potential and high extinction coefficient. An
      effective colorimetric assay for H2O2 is reported here based on the finding that
      H2O2 can induce the shape transformation of citrate-capped iAg NPs with the help
      of citrate. The substantial shape variation affords an apparent surface plasmon
      resonance (SPR) shift, accompanied by a vivid color change from light yellow to
      mauve. The color change can be observed visually if the concentration of H2O2 is
      2 MUM or higher. A good linear relationship was obtained over the concentration
      range of 0.2-32 MUM with a limit of detection of 90 nM. By making use of glucose
      oxidase, the method is further extended to glucose detection. Glucose at a
      concentration as low as 10 MUM can be well determined with bare eyes. Benefitting
      from the high selectivity, the detection of glucose in human serum is realized,
      and the results are in good agreement with those provided by a clinical analyzer.
      Graphical abstract Schematic presentation of a colorimetric assay for H2O2 and
      glucose based on citrate-promoted H2O2-mediated shape transformation of the
      isotropic silver nanoparticles (Ag NPs). The shape variation of isotropic Ag NPs
      induces a color change from light yellow to mauve.

PMID- 29594684
TI  - Human Adipose Tissue Stem Cells Promote the Growth of Acute Lymphoblastic
      Leukemia Cells in NOD/SCID Mice.
AB  - In this study, the effect of adipose tissue stem cells (ASCs) on the growth of
      acute lymphoblastic leukemia (ALL) cells was examined in an in vivo model. We
      established ALL cell lines expressing firefly luciferase (ALL/fLuc) by lentiviral
      infection that were injected intraperitoneally to NOD/SCID mice. The luciferase
      activities were significantly higher in mice co-injected with 105 ALL/fLuc cells
      and ASCs than in those injected with ALL/fLuc cells alone. Co-injection of 105
      ALL/fLuc cells and ASCs in differing ratios into mice gradually increased the
      bioluminescence intensity in all groups, and mice co-injected with 1 or 2 * 106
      ASCs showed higher bioluminescence intensity than those receiving lower numbers.
      Interestingly, in the mice injected with 105 or 107 ALL/fLuc cells alone, the
      formation of tumor masses was not observed for at least five weeks. Moreover, co
      injection of 107 ALL/fLuc cells and 5 * 105 ASCs into mice increased the
      bioluminescence intensity in all groups, and showed significantly higher
      bioluminescence intensity compared to mice co-injected with human normal
      fibroblast HS68 cells. Overall, ASCs promote the growth of ALL cells in vivo,
      suggesting that ASCs negatively influence hematologic malignancy, which should be
      considered in developing cell therapy using ASCs.

PMID- 29594685
TI  - Climate change impacts detection in dry forested ecosystem as indicated by
      vegetation cover change in -Laikipia, of Kenya.
AB  - The objective of the study was to detect and identify land cover changes in
      Laikipia County of Kenya that have occurred during the last three decades. The
      land use types of study area are six, of which three are the main and the other
      three are the minor. The main three, forest, shrub or bush land and grassland,
      changed during the period, of which grasslands reduced by 5864 ha (40%), forest
      by 3071 ha (24%) and shrub and bush land increased by 8912 ha (43%). The other
      three minor land use types were bare land which had reduced by 238 ha (45%),
      river bed vegetation increased by 209 ha (72%) and agriculture increased by 52 ha
      (600%) over the period decades. Differences in spatiotemporal variations of
      vegetation could be largely attributed to the effects of climate factors,
      anthropogenic activities and their interactions. Precipitation and temperature
      have been demonstrated to be the key climate factors for plant growth and
      vegetation development where rainfall decreased by 200 mm and temperatures
      increased by 1.5  degrees C over the period. Also, the opinion of the community
      on the change of land use and management was attributed to climate change and
      also adaptation strategies applied by the community over time. For example unlike
      the common understanding that forest resources utilisation increases with
      increasing human population, Mukogodo dry forested ecosystem case is different in
      that the majority of the respondents (78.9%) reported that the forest resource
      use was more in that period than now and also a similar majority (74.2%) had the
      same opinion that forest resource utilisation was low compared to last 30 years.
      In Yaaku community, change impacts were evidenced and thus mitigation measures
      suggested to address the impacts which included the following: controlled bush
      management and indigenous grass reseeding programme were advocated to restore
      original grasslands, and agricultural (crop farming) activities are carried out
      in designated areas outside the forest conservation areas (ecosystem zoning) all
      in consultation with government (political class), community and other
      stakeholders. Groups are organised (environmental management committee) to
      address conservation, political and vulnerability issues in the pastoral dry
      forested ecosystem which will sustain pastoralism in the ecosystem.

PMID- 29594686
TI  - Copper nanoclusters capped with tannic acid as a fluorescent probe for real-time
      determination of the activity of pyrophosphatase.
AB  - The authors show that copper nanoclusters capped with tannic acid (TA-CuNCs) are
      viable fluorescent probes for the determination of the activity of
      pyrophosphatase (PPase). The fluorescence of the TA-CuNCs is quenched by Fe(III)
      but restored on subsequant addition of pyrophosphate (PPi). If, however, PPi is
      split by PPase into two phosphate ions, the fluorescence of the TA-CuNCs is
      quenched again. Under optimized conditions, fluorescence intensity linearly
      correlates with the activity of PPase in the range from 0.50 to 18.0 U L-1 with a
      detection limit of 0.19 U L-1. The method was employed to the determination of
      PPase in spiked human serum samples and gave satisfactory results. Graphical
      abstract Schematic illustration of fluorometric assay for PPase activity. It is
      based on the finding that pyrophosphate (PPi) can restore the Fe3+-quenched TA
      CuNC fluorescence. PPi is formed by enzymatic action of PPasei.

PMID- 29594687
TI  - Assessment of Ablative Therapies in Swine: Response of Respiratory Diaphragm to
      Varying Doses.
AB  - Ablation is a common procedure for treating patients with cancer, cardiac
      arrhythmia, and other conditions, yet it can cause collateral injury to the
      respiratory diaphragm. Collateral injury can alter the diaphragm's properties
      and/or lead to respiratory dysfunction. Thus, it is important to understand the
      diaphragm's physiologic and biomechanical properties in response to ablation
      therapies, in order to better understand ablative modalities, minimize
      complications, and maximize the safety and efficacy of ablative procedures. In
      this study, we analyzed physiologic and biomechanical properties of swine
      respiratory diaphragm muscle bundles when exposed to 5 ablative modalities. To
      assess physiologic properties, we performed in vitro tissue bath studies and
      measured changes in peak force and baseline force. To assess biomechanical
      properties, we performed uniaxial stress tests, measuring force-displacement
      responses, stress-strain characteristics, and avulsion forces. After treating the
      muscle bundles with all 5 ablative modalities, we observed dose-dependent
      sustained reductions in peak force and transient increases in baseline force-but
      no consistent dose-dependent biomechanical responses. These data provide novel
      insights into the effects of various ablative modalities on the respiratory
      diaphragm, insights that could enable improvements in ablative techniques and
      therapies.

PMID- 29594688
TI  - Coupled Morphological-Hemodynamic Computational Analysis of Type B Aortic
      Dissection: A Longitudinal Study.
AB  - Progressive false lumen aneurysmal degeneration in type B aortic dissection
      (TBAD) is a complex process with a multi-factorial etiology. Patient-specific
      computational fluid dynamics (CFD) simulations provide spatial and temporal
      hemodynamic quantities that facilitate understanding this disease progression. A
      longitudinal study was performed for a TBAD patient, who was diagnosed with the
      uncomplicated TBAD in 2006 and treated with optimal medical therapy but received
      surgery in 2010 due to late complication. Geometries of the aorta in 2006 and
      2010 were reconstructed. With registration algorithms, we accurately quantified
      the evolution of the false lumen, while with CFD simulations we computed several
      hemodynamic indexes, including the wall shear stress (WSS), and the relative
      residence time (RRT). The numerical fluid model included large eddy simulation
      (LES) modeling for efficiently capturing the flow disturbances induced by the
      entry tears. In the absence of complete patient-specific data, the boundary
      conditions were based on a specific calibration method. Correlations between
      hemodynamics and the evolution field in time obtained by registration of the
      false lumen are discussed. Further testing of this methodology on a large cohort
      of patients may enable the use of CFD to predict whether patients, with
      originally uncomplicated TBAD, develop late complications.

PMID- 29594689
TI  - Development of a Metric for Predicting Brain Strain Responses Using Head
      Kinematics.
AB  - Diffuse brain injuries are caused by excessive brain deformation generated
      primarily by rapid rotational head motion. Metrics that describe the severity of
      brain injury based on head motion often do not represent the governing physics of
      brain deformation, rendering them ineffective over a broad range of head impact
      conditions. This study develops a brain injury metric based on the response of a
      second-order mechanical system, and relates rotational head kinematics to strain
      based brain injury metrics: maximum principal strain (MPS) and cumulative strain
      damage measure (CSDM). This new metric, universal brain injury criterion (UBrIC),
      is applicable over a broad range of kinematics encountered in automotive crash
      and sports. Efficacy of UBrIC was demonstrated by comparing it to MPS and CSDM
      predicted in 1600 head impacts using two different finite element (FE) brain
      models. Relative to existing metrics, UBrIC had the highest correlation with the
      FE models, and performed better in most impact conditions. While UBrIC provides a
      reliable measurement for brain injury assessment in a broad range of head impact
      conditions, and can inform helmet and countermeasure design, an injury risk
      function was not incorporated into its current formulation until validated strain
      based risk functions can be developed and verified against human injury data.

PMID- 29594690
TI  - Associations Between Copper and Zinc and Risk of Hypertension in US Adults.
AB  - Evidence linking copper and zinc to hypertension are limited and conflicting.
      Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014
      were used. Zinc and copper intake from diet and supplements was assessed with 24
      h dietary recall. Hypertension was defined as systolic blood pressure (SBP) >=
      140 mmHg/diastolic blood pressure (DBP) >= 90 mmHg/treatment with hypertensive
      medications. In a sensitivity analysis, according to the 2017 American College of
      Cardiology and American Heart Association guideline, hypertension was also
      defined as SBP >= 130 mmHg/DBP >= 80 mmHg/treatment with hypertensive
      medications. A total of 17,811 adults (8430 men and 9381 women) were included.
      After adjustment for age, gender, body mass index (BMI), race, educational level,
      smoking status, family income, and total daily energy intake, the OR of
      hypertension for highest vs. lowest quartile intake of copper, zinc, and
      copper/zinc ratio was 1.11 (0.90-1.37), 1.11 (0.90-1.35), and 0.95 (0.81-1.11),
      respectively. In stratified analysis by BMI (< 25 kg/m2, 25-30 kg/m2, > 30
      kg/m2), no significant association was found between hypertension and intakes of
      copper, zinc, and copper/zinc ratio (highest vs. lowest quartile) in multivariate
      analysis. In multivariate analysis, the OR of hypertension for highest vs. lowest
      quartile levels of serum copper, zinc, and copper/zinc ratio was 1.11 (0.61
      2.04), 1.43 (0.84-2.44), and 0.68 (0.34-1.33), respectively. Similar results were
      found in the sensitivity analysis. Zinc and copper might be not independently
      associated with hypertension in US adults.

PMID- 29594691
TI  - A Review on the Role of Chromium Supplementation in Ruminant Nutrition-Effects on
      Productive Performance, Blood Metabolites, Antioxidant Status, and
      Immunocompetence.
AB  - With the increase in the global herd, the use of metabolic modifiers has become
      an important area for many researchers looking for a supraphysiological diet to
      improve production parameters. For improving the performance of high yielding
      cows, the optimal balance of all nutrients including microminerals is important.
      Chromium (Cr) is one of the important micronutrients which plays an important
      role in metabolism of ruminants. Experimental studies have found that Cr could
      change performance, immune responses, glucose and fatty acid metabolism, and
      antioxidant status in dairy cows. In some studies, Cr supplementation improved
      dry matter intake, milk production, and milk composition of dairy cows in the
      early, mid, or late stage of lactation. Also, in some studies, performance of
      growing animal, immune response, and some blood parameters responded positively
      to Cr supplementation. In conclusion, the effects of Cr supplementation on
      performance of ruminants are inconsistent; however, its long-term effects on
      health, productivity, immune system, and antioxidant activity of ruminants still
      need to be investigated.

PMID- 29594692
TI  - Effect of Organic Selenium Supplementation on Selenium Status, Oxidative Stress,
      and Antioxidant Status in Selenium-Adequate Dairy Cows During the Periparturient
      Period.
AB  - The periparturient period represents a stressful time for dairy cows as they
      transition from late gestation to early lactation. Oxidation stress occurs during
      this period owing to the increased metabolic activity. Antioxidants
      supplementation slightly above the suggested requirements may be beneficial in
      relieving this kind of stress. The objective of this study was to determine
      whether supplementing selenium (Se) yeast to diets with adequate Se
      concentrations affects Se status, oxidative stress, and antioxidant status in
      dairy cows during the periparturient period. Twenty multiparous Holstein cows
      were randomly divided into two groups with ten replicates in each group. During
      the last 4 weeks before calving, cows were fed Se-yeast at 0 (control) or 0.3 mg
      Se/kg dry matter (Se-yeast supplementation), in addition to Na selenite at 0.3 mg
      Se/kg dry matter in their rations. The concentrations of Se, reactive oxygen
      species (ROS), hydrogen peroxide (H2O2), hydroxyl radical, malonaldehyde (MDA),
      alpha-tocopherol and glutathione (GSH), the activities of glutathione peroxidase
      (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), and the total
      antioxidant capacity (T-AOC) in plasma or erythrocyte of dairy cows were measured
      at 21 and 7 days prepartum, and at 7 and 21 days postpartum. Cows fed Se-yeast
      supplement during the last 4 weeks of gestation had higher plasma Se and lower
      MDA concentrations at 7 days prepartum, and at 7 and 21 days postpartum, and had
      higher whole blood Se and lower plasma ROS and H2O2 concentrations at 7 and 21
      days postpartum compared with control cows. Se-yeast supplementation increased
      plasma and erythrocyte GSH-Px activities and erythrocyte GSH concentration at 7
      days postpartum as compared to Se-adequate control cows. Compared with control
      cows, the enhanced SOD and CAT activities, increased alpha-tocopherol and GSH
      concentrations, and improved T-AOC in plasma at 7 and 21 days postpartum in Se
      yeast-supplemented cows were also observed in this study. The results indicate
      that feeding Se-adequate cows a Se-yeast supplement during late gestation
      increases plasma Se status, improves antioxidant function, and relieves
      effectively oxidative stress occurred in early lactation.

PMID- 29594693
TI  - Quality of information on the Internet-has a decade made a difference?
AB  - BACKGROUND: While patients accessing the Internet can be a positive step towards
      health literacy and self-efficacy, these resources vary in quality. AIMS: In
      2007, Kulasegarah et al. assessed the information available to patients on the
      Internet on three common ENT procedures (tonsillectomy, septoplasty, and
      myringoplasty), looking at the quality of the information in terms of
      completeness and accuracy. This is a follow-on study to examine how this
      information has changed after 10 years. METHODS: Following a Google search, the
      top 20 webpages on each of the three ENT procedures, tonsillectomy, septoplasty,
      and myringoplasty, were analyzed. RESULTS: Webpages gave on average 50.6% of the
      critical information a patient should know prior to undergoing surgery. This is a
      drop from 2007 (65.5%). Over 96.8% were found to have no inaccuracies identified
      on the available information provided on the websites. This was slightly higher
      than in 2007 (94.7%). YouTube (10%) and hospital webpages (10%) were among the
      new subcategories that were not present in the 2007 study. CONCLUSIONS: Due to
      the reduced completeness of information available to patients online, it is
      important that health professionals direct patients to appropriate websites if
      they wish to do their own research.

PMID- 29594694
TI  - Surface enhanced Raman detection of the colon cancer biomarker cytidine by using
      magnetized nanoparticles of the type Fe3O4/Au/Ag.
AB  - Cytidine is regarded as an early marker of colon cancer. The authors describe a
      surface enhanced Raman scattering (SERS) technique to detect trace levels of
      cytidine in urine. The Raman band at 784 cm-1 can be acquired best. Compared to
      earlier methods, an improvement in detection sensitivity by a factor of 6.2 * 105
      is achieved by using a magnetically induced method in which cytidine is captured
      in the vicinity of the SERS hot spots of the type Fe3O4/Au/Ag. Cytidine can be
      quantified at 1 nM levels by this method which is simple and reliable. Graphical
      Abstract Clusters consisting of magnetite (Fe3O4) nanoparticles, gold
      nanoparticles and silver nanoparticles were prepared and used in a SERS based
      method for detection of cytidine in urine by using magnetic improvement. The
      lowest detectable concentration of cytidine are at the nM level.

PMID- 29594695
TI  - Magnetic nanoparticle based solid-phase extraction of heavy metal ions: A review
      on recent advances.
AB  - This review (with 151 refs) focuses on recent progress that has been made in
      magnetic nanoparticle-based solid phase extraction (SPE), pre-concentration and
      speciation of heavy metal ions. In addition, it discusses applications to complex
      real samples such as environmental, food, and biological matrices. The
      introduction addresses current obstacles and limitations associated with
      established SPE approaches and discusses the present state of the art in
      different formats of off-line and on-line SPE. The next section covers magnetized
      inorganic nanomaterials for use in SPE, with subsections on magnetic silica,
      magnetic alumina and titania, and on magnetic layered double oxides. A further
      section treats magnetized carbonaceous nanomaterials for use in SPE, with
      subsections on magnetic graphene and/or graphene oxides, magnetic carbon
      nanotubes and magnetic carbon nitrides. We then discuss the progress made in SPE
      based on the use of magnetized organic polymers (mainly non-imprinted and ion
      imprinted polymer). This is followed by shorter sections on the use of magnetized
      metal organic frameworks, magnetized ionic liquids and magnetized biosorbents.
      All sections include discussions of the nanomaterials in terms of selectivity,
      sorption capacity, mechanisms of sorption and common routes for material
      synthesis. A concluding section addresses actual challenges and discusses
      perspective routes towards further improvements. Graphical abstract An overview
      on booster nanomaterials (ionic liquids, inorganic, organic and biological
      materials, and metal-organic frameworks) for use in magnetic nanoparticle-based
      solid-phase extraction of heavy metal ions.

PMID- 29594696
TI  - Voltammetric determination of 5-hydroxytryptamine based on the use of platinum
      nanoparticles coated with molecularly imprinted silica.
AB  - The authors describe an electrochemical sensor for the determination of 5
      hydroxytryptamine (5-HT; serotonin). It is based on the use of platinum
      nanoparticles (PtNPs) coated with molecularly imprinted silica (MIS). The MIS
      coated PtNPs were prepared from 5-HT, PtNPs, phenyltrimethoxysilane and
      tetraethoxysilane that act as template, support, functional monomer and cross
      linker, respectively. The MIS-coated PtNPs were characterized by Fourier transfer
      infrared spectroscopy and transmission electron microscopy. The MIS-coated PtNPs
      were drop-cast onto a glassy carbon electrode (GCE) to obtain an electrochemical
      sensor for 5-HT which exhibited fast response and high recognition ability for 5
      HT. The imprinting factor of this electrode for 5-HT is 4.12, which is higher
      than that for its analogs. Under optimized conditions and at a typical working
      potential of 0.29 V (vs. Hg/Hg2Cl2), the electrode has a linear response in the
      0.05-80 MUM 5-HT concentration range and a 0.02 MUM detection limit. The
      electrode was successfully applied to the determination of 5-HT in human serum
      samples. Graphical Abstract Molecularly imprinted silica-coated platinum
      nanoparticles were prepared using surface imprinting technique. A glassy carbon
      electrode modified with the surface imprinted material exhibits fast response in
      detecting 5-hydroxytryptamine, a low detection limit, good selectivity,
      reproducibility and stability.

PMID- 29594697
TI  - A highly selective colorimetric sulfide assay based on the inhibition of the
      peroxidase-like activity of copper nanoclusters.
AB  - The authors report that sulfide ions are capable of inhibiting the peroxidase
      like activity of copper nanoclusters (CuNCs). The catalytic activity of CuNCs
      toward the oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine
      by H2O2 is remarkably decreased in the presence of sulfide. Based on this
      finding, a colorimetric assay was developed for the rapid determination of
      sulfide. Best operated at a wavelength of 652 nm, it has a 0.5 MUM detection
      limit. The method is highly selective and has been successfully applied to the
      quantification of sulfide in environmental water samples. Graphical abstract The
      catalytic activity of CuNCs toward the oxidation of 3,3',5,5'
      tetramethylbenzidine by H2O2 is remarkably decreased in the presence of sulfide
      ions. This finding has been applied to design a method for colorimetric
      quantification of sulfide ions in environmental samples.

PMID- 29594698
TI  - An aptamer-based colorimetric lead(II) assay based on the use of gold
      nanoparticles modified with dsDNA and exonuclease I.
AB  - The authors describe a colorimetric method for the sensitive and selective
      detection of Pb(II). It is based on the use exonuclease I (Exo I), a Pb(II)
      binding aptamer bound to gold nanoparticles (AuNPs), and a DNA strand that
      complementary to the aptamer. In the absence of Pb(II), the dsDNA on the AuNPs
      prevents aggregation of the AuNPs in the presence of NaCl. In the presence of
      Pb(II), however, the aptamer binds Pb(II) and complementary strand is released
      and digested by Exo I. As a result, the solution of AuNPs undergoes a color
      change from red to purple if salt is added to the sample. The assay is selective
      for Pb(II) and has a limit of detection as low as 2.4 nM. It was successfully
      applied to the determination of Pb(II) in spiked tap water. Graphical abstract
      Schematic presentation of the aptamer based method for Pb2+ detection via salt
      induced aggregation of gold nanoparticles and colorimetric quantitation.

PMID- 29594699
TI  - Hemoglobin-incorporated iron quantum clusters as a novel fluorometric and
      colorimetric probe for sensing and cellular imaging of Zn(II) and cysteine.
AB  - The authors describe a novel water-soluble, stable, biocompatible, and highly
      fluorescent probe consisting of iron quantum clusters incorporated into human
      adult hemoglobin (Hb-FeQCs). The Hb-FeQCs were characterized by various
      spectroscopic techniques. The probe displays strong absorption and yellow
      fluorescence with a peak centered at 567 nm (photo-excited at 460 nm). The Hb
      FeQCs show excellent photostability over a wide range of pH values (5-12), even
      in the presence of high electrolyte concentrations. A colorimetric and a
      fluorometric method were worked out for the quantitation Zn(II) and cysteine in
      aqueous solution. Zinc ions induce a visible color change from brown to yellow.
      The sensitivity of Hb-FeQCs towards other metal ions was negligible, with the
      exception of Co2+ and Cu2+, which caused a modest interference. The Hb-FeQCs were
      exploited in a sensitive and selective turn-on fluorescence assay for Zn2+. It is
      also found that cysteine quenches the fluorescence of the Hb-FeQCs/Zn(II)
      complex. Under the optimized conditions, the probe has a linear response in the
      0.04 to 2.2 MUM Zn(II) concentration range, with a 48 nM detection limit.
      Response to cysteine is linear in the 1-60 MUM concentration range, with a 0.25
      MUM limit of detection. This fluorescent probe undergoes fluorescent emission
      intensity enhancement upon binding to zinc ions in living normal human fibroblast
      cells under visible lamp. The cellular imaging capability and very low
      cytotoxicity of this soluble iron quantum clusters can be potentially extended as
      an exciting sub-nanoplatform with promising biomaterial applications. Graphical
      abstract Schematic of yellow-emitting iron quantum clusters in hemoglobin matrix
      (Hb-FeQCs) were characterized and successfully applied for sensing zinc(II) and
      cysteine. The act as an on-off fluorescent probe and can be applied to image zinc
      ions in human fibroblast cells under visible light.

PMID- 29594700
TI  - Simultaneous voltammetric determination of guanine and adenine by using a glassy
      carbon electrode modified with a composite consisting of carbon quantum dots and
      overoxidized poly(2-aminopyridine).
AB  - A composite consisting of carbon quantum dots (CQDs) and overoxidized poly(2
      aminopyridine) (PAPox) was deposited on a glassy carbon electrode (GCE) through
      electrochemical polymerization and electrochemical oxidation. The modified GCE
      was used for the simultaneous determination of guanine and adenine.
      Electrochemical responses to guanine and adenine were investigated by cyclic
      voltammetry and differential pulse voltammetry. Owing to the synergistic effect
      of CQDs and PAPox, two oxidation peaks can be observed, with peaks at 0.81 and
      1.13 V (vs. SCE) for guanine and adenine, respectively. The current at the
      respective peaks has a linear dependence on the concentrations of guanine in the
      range from 1.0 to 65 MUM, and of adenine in the range from 2.0 to 70 MUM. The
      respective detection limits are 0.51 and 0.39 MUM (at an S/N ratio of 3). The
      modified GCE is selective, reproducible and stable. Graphical abstract Schematic
      of the preparation of a glassy carbon electrode modified with carbon quantum dots
      and overoxidized poly(2-aminopyridine (CQD/PAPox/GCE), and its application for
      the simultaneous determination of guanine and adenine.

PMID- 29594701
TI  - Associations Between Patterns of Sexual Initiation, Sexual Partnering, and Sexual
      Health Outcomes from Adolescence to Early Adulthood.
AB  - The goal of this study was to examine, in a nationally representative sample,
      relationships between various sexual initiation patterns, subsequent sexual
      partnerships, and related health outcomes from adolescence through early
      adulthood. Data were from a subset of 6587 respondents from the National
      Longitudinal Study of Adolescent to Adult Health. Bivariate analyses and adjusted
      logistic and ordinary least squares regression models were used to determine
      associations between membership in three sexual initiation classes, lifetime
      sexual partner counts, and multiple health outcomes, including lifetime sexually
      transmitted infection or disease (STI/STD) diagnosis, lifetime unintended
      pregnancy, and romantic relationship quality. Broadly, having fewer lifetime
      sexual partners was associated with lower odds of STI/STD diagnosis and
      unintended pregnancy, and better relationship quality; however, findings also
      indicated both within and between sexual initiation class differences in the
      relationship between lifetime sexual partners and all three health outcomes. In
      particular, results showed little variation in health outcomes by sexual
      partnering among those who postponed sexual activity, but members of the class
      characterized by early and atypical sexual initiation patterns who had fewer
      lifetime partners exhibited better health outcomes than most other initiation
      groups. These results show that while both sexual initiation and partnering
      patterns add important information for understanding sexual health from
      adolescence to early adulthood, partnering may be more relevant to these sexual
      health outcomes. Findings indicate a need for more comprehensive sexuality
      education focused on sexual risk reduction and promotion of relationship skills
      among adolescents and adults.

PMID- 29594702
TI  - Alterations in Body Uneasiness, Eating Attitudes, and Psychopathology Before and
      After Cross-Sex Hormonal Treatment in Patients with Female-to-Male Gender
      Dysphoria.
AB  - Body dissatisfaction plays an important role in the development of psychiatric
      problems such as eating disorders as well as gender dysphoria (GD). Cross-sex
      hormonal treatment (CHT) alleviates the dissatisfaction by making various changes
      in the body. We examined the alteration of body uneasiness, eating attitudes and
      behaviors, and psychological symptoms longitudinally in Turkish participants with
      female-to-male gender dysphoria (FtM GD) after CHT. Thirty-seven participants
      with FtM GD and 40 female controls were asked to complete the Body Uneasiness
      Test to explore different areas of body-related psychopathology, the Eating
      Attitudes Test to assess eating disturbances, and the Symptom Checklist-90
      Revised to measure psychological state, both before CHT and after 6 months of CHT
      administration. The baseline mean body weight, BMI scores, body uneasiness
      scores, and general psychopathological symptoms of participants with FtM GD were
      significantly higher than female controls, whereas baseline eating attitudes and
      behaviors were not significantly different. Over time, FtM GD participants' mean
      body weight and BMI scores increased, body uneasiness and general
      psychopathological symptoms decreased, and eating attitudes and behaviors had not
      changed at 24th weeks following CHT administration compared to baseline. CHT may
      have a positive impact on body uneasiness and general psychopathological symptoms
      in participants with FtM GD. However, CHT does not have an impact on eating
      attitudes and behaviors.

PMID- 29594703
TI  - Risk factors for shunt dependency in patients suffering from spontaneous, non
      aneurysmal subarachnoid hemorrhage.
AB  - Patients presenting with spontaneous, non-aneurysmal subarachnoid hemorrhage
      (SAH) achieve better outcomes compared to patients with aneurysmal SAH.
      Nevertheless, some patients develop shunt-dependent hydrocephalus during
      treatment course. We therefore analyzed our neurovascular database to identify
      factors determining shunt dependency after non-aneurysmal SAH. From 2006 to 2016,
      131 patients suffering from spontaneous, non-aneurysmal SAH were admitted to our
      department. Patients were stratified according to the distribution of cisternal
      blood into patients with perimesencephalic SAH (pSAH) versus non
      perimesencephalic SAH (npSAH). Outcome was assessed according to the modified
      Rankin Scale (mRS) at 6 months and stratified into favorable (mRS 0-2) versus
      unfavorable (mRS 3-6). A multivariate analysis was performed to identify
      predictors of shunt dependency in patients suffering from non-aneurysmal SAH.
      Overall, 18 of 131 patients suffering from non-aneurysmal SAH developed shunt
      dependency (14%). In detail, patients with npSAH developed significantly more
      often shunt dependency during treatment course, when compared to patients with
      pSAH (p = 0.02). Furthermore, patients with acute hydrocephalus, presence of
      intraventricular hemorrhage, presence of clinical vasospasm, and anticoagulation
      medication prior SAH developed significantly more often shunt dependency, when
      compared to patients without (p < 0.0001). However, "acute hydrocephalus" was the
      only significant and independent predictor for shunt dependency in all patients
      with non-aneurysmal SAH in the multivariate analysis (p < 0.0001). The present
      study identified acute hydrocephalus with the necessity of CSF diversion as
      significant and independent risk factor for the development of shunt dependency
      during treatment course in patients suffering from non-aneurysmal SAH.

PMID- 29594704
TI  - Bioprinted gelatin hydrogel platform promotes smooth muscle cell contractile
      phenotype maintenance.
AB  - Three dimensional (3D) bioprinting has been proposed as a method for fabricating
      tissue engineered small diameter vascular prostheses. This technique not only
      involves constructing the structural features to obtain a desired pattern but the
      morphology of the pattern may also be used to influence the behavior of seeded
      cells. Herein, we 3D bioprinted a gelatin hydrogel microchannel construct to
      promote and preserve the contractile phenotype of vascular smooth muscle cells
      (vSMCs), which is crucial for vasoresponsiveness. The microchanneled surface of a
      gelatin hydrogel facilitated vSMC attachment and an elongated alignment along the
      microchannel direction. The cells displayed distinct F-actin anisotropy in the
      direction of the channel. The vSMC contractile phenotype was confirmed by the
      positive detection of contractile marker gene proteins (alpha-smooth muscle actin
      (alpha-SMA) and smooth muscle-myosin heavy chain (SM-MHC)). Having demonstrated
      the effectiveness of the hydrogel channels bioprinted on a film, the bioprinting
      was applied radially to the surface of a 3D tubular construct by integrating a
      rotating mandrel into the 3D bioprinter. The hydrogel microchannels printed on
      the 3D tubular vascular construct also orientated the vSMCs and strongly promoted
      the contractile phenotype. Together, our study demonstrated that microchannels
      bioprinted using a transglutaminase crosslinked gelatin hydrogel, could
      successfully promote and preserve vSMC contractile phenotype. Furthermore, the
      hydrogel bioink could be retained on the surface of a rotating polymer tube to
      print radial cell guiding channels onto a vascular graft construct.

PMID- 29594705
TI  - Gold nanoparticle-based colorimetric ELISA for quantification of ractopamine.
AB  - The work describes a gold nanoparticle-based colorimetric enzyme-linked
      immunosorbent assay (ELISA) for ractopamine. The ELISA is based on an indirect
      competitive approach. In the presence of ractopamine, gold(III) ions are oxidized
      by H2O2 to form red AuNPs. On the other hand, the AuNP in solution are purple
      blue due to aggregation if the sample does not contain ractopamine. The
      absorption, best measured at 560 nm, increases linearly in the 2 to 512 ng.mL-1
      ractopamine concentration range, and the detection limit is as low as 0.35 ng.mL
      1 in urine. Ractopamine can also be detected visually, even in the presence of
      other beta-agonists and antibiotics. The results obtained by this method are
      consistent with those obtained by LC-MS/MS as demonstrated by analysis of sheep
      urine. The ELISA method described here is inexpensive, easy-to-use, and suitable
      for rapid screening of ractopamine in animal samples. Graphical abstract
      Schematic presentation of a colorimetric indirect competitive immunoassay for
      ractopamine. It is based on the use of catalase labeled IgG and the measurement
      of the absorption of red gold nanoparticles (AuNPs) that are generated by the
      reaction of gold ions with H2O2. In the absence of ractopamine, the solution
      becomes blue.

PMID- 29594706
TI  - Visible light photoelectrochemical aptasensor for chloramphenicol by using a TiO2
      nanorod array sensitized with Eu(III)-doped CdS quantum dots.
AB  - A visible-light driven photoelectrochemical (PEC) aptasensor is described that is
      capable of detecting chloramphenicol (CAP). It is based on the use of a TiO2
      based nanorod array (NRA) sensitized with Eu(III)-doped CdS quantum dots. The NRA
      absorbs visible-light and while strongly depressing the recombination of
      photogenerated charges, thereby improving photo-to-current conversion efficiency.
      The introduction of Eu(III) ions promotes the charge transformation and
      utilization, and this results in a further increase of photocurrent. The NRA was
      employed as the photoactive material for the fabrication of a PEC aptasensor. CAP
      binding aptamers were immobilized on a fluorine-doped tin oxide (FTO) electrode
      that was modified with the NRA. The aptasensor was applied to the determination
      of CAP by monitoring the decrease in photocurrent (at a typical voltage of 0 V)
      that is caused by the formation of the aptamer-CAP complex. Under optimal
      conditions, the response is linear in the 1.0 pM to 3.0 nM CAP concentration
      range, with a detection limit of 0.36 pM (at S/N = 3). The method was applied to
      the determination of CAP in spiked milk samples where it gave satisfactory
      results. Graphical abstract Schematic presentation of the fabrication of a
      visible-light driven photoelectrochemical aptasensor based on the use of a TiO2
      nanorod array sensitized with Eu(III)-doped CdS quantum dots. It was applied to
      the determination of chloramphenicol with good selectivity and high sensitivity.
      TiO2 NRA: TiO2 nanorod array; FTO: fluorine-doped tin oxide; CdS:Eu3+ QDs:
      Eu(III)-doped CdS quantum dots; BSA: bovine serum albumin; CAP: chloramphenicol.

PMID- 29594707
TI  - Paper-based chemiluminescence immunodevice for the carcinoembryonic antigen by
      employing multi-enzyme carbon nanosphere signal enhancement.
AB  - A paper-based chemiluminescence (CL) immunodevice is described for sensitive
      determination of the carcinoembryonic antigen (CEA). Capture antibody (Ab1) was
      first immobilized on the paper-based chip after plasma treatment of the paper
      surface. Next, carbon nanospheres functionalized with horse radish peroxidase
      (HRP) were attached as a signal antibody label. Strongly enhanced CL was achieved
      from the HRP catalyzed luminol/H2O2 CL system when using a sandwich immunoassay
      format. CEA can be quantified with a lower detection limit of 3 pg.mL-1. The
      method displays an almost 10-fold increased sensitivity in comparison to a
      commercial Ab2-HRP based kit. Conceivably, this sensitive method may also be
      extended by designing sensitive assays for other biomarkers of interest in point
      of-care diagnostics. Graphical abstract Schematic of a paper-based
      chemiluminescence (CL) immunodevice for the determination of the carcinoembryonic
      antigen (CEA) by applying a multi-enzyme carbon nanosphere signal enhancement
      strategy.

PMID- 29594708
TI  - Endoscopic ultrasound-guided fine-needle aspiration of enlarged adrenals in
      patients with pyrexia of unknown origin: A single-center experience of 52 cases.
AB  - BACKGROUND: Fine-needle aspiration (FNA) of adrenals is needed in patients with
      pyrexia of unknown origin (PUO) and adrenal enlargement in absence of other
      diagnostic clues. Adrenals are easily accessible by endoscopic ultrasound (EUS)
      due to proximity; however, there is no systemic study available on FNA of
      adrenals in patients with PUO. The aim of this study was to evaluate the
      diagnostic yield and safety of EUS-FNA of enlarged adrenal in patients with PUO.
      METHODS: Data was analyzed from October 2010 to September 2016 at a single
      tertiary care center in northern India. EUS-FNA of enlarged adrenals was done in
      52 patients for the etiological diagnosis of PUO in whom a definitive diagnosis
      could not be made with other means. RESULTS: The mean age was 48+/-14 years; 36
      were males and 16 were females. EUS-FNA was done from the left adrenal in 50
      patients and from the right sample in 2 patients. A technical success was
      achieved in 100% cases. The 19-G needle was used in the majority (75%) to the
      presence of necrotic areas in adrenals; median numbers of passes were 2. The
      cytopathological diagnoses were tuberculosis (n = 36), histoplasmosis (n = 13),
      lymphoma (n = 2), and metastasis from undiagnosed neuroendocrine tumor of lung (n
      = 1). Thus, a diagnosis could be made in 52/52 (100%) patients. None of the
      patients had any procedure-related complications. CONCLUSIONS: EUS-FNA is a safe
      and effective method for evaluating etiology of PUO in patients with adrenal
      enlargement.

PMID- 29594709
TI  - Digital rectal examination-A reliable screening tool for dyssynergic defecation.

PMID- 29594710
TI  - Correction to: Effect of a Preparation of Four Probiotics on Symptoms of Patients
      with Irritable Bowel Syndrome: Association with Intestinal Bacterial Overgrowth.
AB  - The original version of this article contained mistakes, and the authors would
      like to correct them. The correct details are given below.

PMID- 29594711
TI  - Validation and Optimization of BIANCA for the Segmentation of Extensive White
      Matter Hyperintensities.
AB  - White matter hyperintensities (WMH) are a hallmark of small vessel diseases
      (SVD). Yet, no automated segmentation method is readily and widely used,
      especially in patients with extensive WMH where lesions are close to the cerebral
      cortex. BIANCA (Brain Intensity AbNormality Classification Algorithm) is a new
      fully automated, supervised method for WMH segmentation. In this study, we
      optimized and compared BIANCA against a reference method with manual editing in a
      cohort of patients with extensive WMH. This was achieved in two datasets: a
      clinical protocol with 90 patients having 2-dimensional FLAIR and an advanced
      protocol with 66 patients having 3-dimensional FLAIR. We first determined
      simultaneously which input modalities (FLAIR alone or FLAIR + T1) and which
      training sets were better compared to the reference. Three strategies for the
      selection of the threshold that is applied to the probabilistic output of BIANCA
      were then evaluated: chosen at the group level, based on Fazekas score or
      determined individually. Accuracy of the segmentation was assessed through
      measures of spatial agreement and volumetric correspondence with respect to
      reference segmentation. Based on all our tests, we identified multimodal inputs
      (FLAIR + T1), mixed WMH load training set and individual threshold selection as
      the best conditions to automatically segment WMH in our cohort. A median Dice
      similarity index of 0.80 (0.80) and an intraclass correlation coefficient of 0.97
      (0.98) were obtained for the clinical (advanced) protocol. However, Bland-Altman
      plots identified a difference with the reference method that was linearly related
      to the total burden of WMH. Our results suggest that BIANCA is a reliable and
      fast segmentation method to extract masks of WMH in patients with extensive
      lesions.

PMID- 29594712
TI  - Fluorometric graphene oxide-based detection of Salmonella enteritis using a
      truncated DNA aptamer.
AB  - The work describes a fluorescence-based study for mapping the highest affinity
      truncated aptamer from the full length sequence and its integration in a graphene
      oxide platform for the detection of Salmonella enteriditis. To identify the best
      truncated sequence, molecular beacons and a displacement assay design are
      applied. In the fluorescence displacement assay, the truncated aptamer was
      hybridized with fluorescein and quencher-labeled complementary sequences to form
      a fluorescence/quencher pair. In the presence of S. enteritidis, the aptamer
      dissociates from the complementary labeled oligonucleotides and thus, the
      fluorescein/quencher pair becomes physically separated. This leads to an increase
      in fluorescence intensity. One of the truncated aptamers identified has a 2-fold
      lower dissociation constant (3.2 nM) compared to its full length aptamer (6.3
      nM). The truncated aptamer selected in this process was used to develop a
      fluorometric graphene oxide (GO) based assay. If fluorescein-labeled aptamer is
      adsorbed on GO via pi stacking interaction, fluorescence is quenched. However, in
      the presence of target (S. enteriditis), the labeled aptamers is released from
      surface to form a stable complex with the bacteria and fluorescence is restored,
      depending on the quantity of bacteria being present. The resulting assay has an
      unsurpassed detection limit of 25 cfu.mL-1 in the best case. The cross reactivity
      to Salmonella typhimurium, Staphylococcus aureus and Escherichia coli is
      negligible. The assay was applied to analyze doped milk samples for and gave good
      recovery. Thus, we believe that the truncated aptamer/graphene oxide platform is
      a potential tool for the detection of S. Enteritidis. Graphical abstract
      Fluorescently labelled aptamer against Salmonella enteritidis was adsorbed on the
      surface of graphene oxide by pi-stacking interaction. This results in quenching
      of the fluorescence of the label. Addition of Salmonella enteritidis restores
      fluorescence, and this effect is used for quantification of this food-borne
      pathogen.

PMID- 29594713
TI  - Ratiometric fluorometric determination of the anthrax biomarker 2,6-dipicolinic
      acid by using europium(III)-doped carbon dots in a test stripe.
AB  - Europium(III)-doped carbon dots (Eu-CDs) were prepared from citric acid and
      europium nitrate via a one-pot pyrolytic method. The Eu-CDs emit intense blue
      fluorescence (with excitation/emission peaks at 365/465 nm), are water soluble
      and biocompatible. On addition of 2,6-dipicolinic acid (DPA; an anthrax
      biomarker), ligand-to-ion energy transfer occurs from DPA to Eu(III) which has a
      red emission peaking at 615 nm. This results in an increase of the intensity of
      the red fluorescence. DPA can be detected by the ratio of fluorescence
      intensities at 616 and 475 nm. The method has an analytical range that extends
      from 5 to 700 nmol.L-1, with a 5 nmol.L-1 detection limit. The Eu-CDs also were
      incorporated into a test paper for visual detection of DPA with a portable UV
      lamp and a smartphone. In this case, the detection limit is 1 MUmol.L-1. The Eu
      CDs internalize well into HeLa cells, and this paves the way to bioimaging.
      Graphical abstract Schematic of a method for visual detection of 2,6-dipicolinic
      acid (DPA, an anthrax biomarker) by using a test stripe impregnated with
      europium(III)-doped carbon dots (Eu-CDs).

PMID- 29594714
TI  - Aptamer based determination of Pb(II) by SERS and by exploiting the reduction of
      HAuCl4 by H2O2 as catalyzed by graphene oxide nanoribbons.
AB  - The authors report that graphene oxide nanoribbons exert a strong catalytic
      effect on the reduction of HAuCl4 by H2O2 to form gold nanoparticles which
      display nanoplasmonic surface enhanced Raman scattering (SERS) activity, Rayleigh
      scattering and absorption. If an aptamer against Pb(II) is present in solution,
      it will bind to the graphene oxide nanoribbons and thereby inhibit their
      catalytic activity. Upon addition of Pb(II), it will bind to the aptamer to form
      stable complexes and release free graphene oxide nanoribbon. These cause the
      surface enhanced Raman scattering intensity at 1615 cm-1 to increase in the
      presence of the molecular probe Victoria Blue B. The SERS signal increases
      linearly in the 0.002-0.075 MUmol.L-1 Pb(II) concentration range, and the
      detection limit is 0.7 nmol.L-1. Toner samples were spiked and then analyzed for
      Pb(II) by this method. Relative standard deviations are between 6.2% and 12.2%,
      and recoveries range from of 86.7%-106.7%. Graphic abstract Based on Pb(II) binds
      to the aptamer to form stable G-quadruplex and release free graphene oxide
      nanoribbon, a sensitive and selective surface enhanced Raman scattering method
      was developed for detection of 0.002-0.075 MUmol.L-1 Pb(II) by using the
      molecular probe Victoria Blue B.

PMID- 29594715
TI  - MoS2 quantum dots modified with a labeled molecular beacon as a ratiometric
      fluorescent gene probe for FRET based detection and imaging of microRNA.
AB  - A dual-channel ratiometric nanoprobe is described for detection and imaging of
      microRNA. It was prepared from MoS2 quantum dots (QDs; with blue emission and
      excitation/emission peaks at 310/398 nm) which acts as both the gene carrier and
      as a donor in fluorescence resonance energy transfer (FRET). Molecular beacons
      containing loops for molecular recognition of microRNA and labeled with
      carboxyfluorescein (FAM) were covalently attached to the MoS2 QDs and serve as
      the FRET acceptor. In the absence of microRNA, the nanoprobe exhibits low FRET
      efficiency due to the close distance between the FAM tag and the QDs.
      Hybridization with microRNA enlarges the distance between QD and beacon. This
      results in an enhancement of the FRET efficiency of the nanoprobe. The ratio of
      green and blue fluorescence (I520/I398) increases linearly in the 5 to 150 nM
      microRNA concentration range in both aqueous solution and diluted artificial
      cerebrospinal fluid. The limit of detection (LOD) is as low as 0.38 nM and 0.52
      nM, respectively. Other features of this nanoprobe include (a) excellent
      resistance to nuclease-induced false positive signals and (b) the option to use
      it for distinguishing different cell lines by in-situ imaging of intracellular
      microRNAs. Graphical abstract Schematic of a dual-channel photoluminescence
      nanoprobe for the determination of microRNA-21 (miR-21) by monitoring the
      microRNA-triggered enhancement of the fluorescence resonance energy transfer
      (FRET) efficiency between MoS2 QDs and carboxyfluorescein-labeled molecular
      beacons.

PMID- 29594716
TI  - Controlled synthesis of polydopamine: A new strategy for highly sensitive
      fluorescence turn-on detection of acetylcholinesterase activity.
AB  - A new water soluble fluorescent coronene probe (CTCA) was synthesized and is
      shown to display strong fluorescence (with excitation/emission maxima at 313/450
      nm) in aqueous solution. Dopamine was oxidized under air to form polydopamine
      (PDA) which quenches the fluorescence of CTCA. The enzyme acetylcholinesterase
      (AChE) is known catalyze the hydrolysis of acetylthiocholine to produce
      thiocholine. Thiocholine inhibits the polymerization of DA, and this leads to
      recovery in CTCA fluorescence. These findings form the basis for a new method for
      detection of AChE activity. The assay has a detection limit as low as 0.05 mU.mL
      1 of AChE. It is highly selective, and other enzymes do no noticeably interfere.
      It was applied to the determination of AChE activity in (spiked) human serum, and
      of AChE inhibitors in (spiked) lake water samples. Graphical abstract Controlled
      synthesis of polydopamine for the highly sensitive and selective sensing of AChE
      activity is reported for the first time.

PMID- 29594717
TI  - Fluorometric determination of dopamine by using molybdenum disulfide quantum
      dots.
AB  - A method is described for the rapid fluorometric determination of dopamine (DA)
      by using molybdenum disulfide quantum dots (MoS2 QDs) that were fabricated via an
      ammonium hydroxide etching method. The probe has a fluorescence (with
      excitation/emission peaks at 267/380 nm) that is quenched by DA with high
      selectivity over various interferences. This is attributed to a reaction that
      occurs between DA and the molybdate ions in pH 9 solutions of MoS2 QDs. The
      formation of organic molybdate complexes and of dopamine-quinone results in
      strong quenching of the fluorescence of the QDs which is due to both electron
      transfer and an inner filter effect. Under the optimum conditions, the assay
      works in the 0.1-100 MUM DA concentration range, with two linear ranges and a 10
      nM detection limit. The method was applied to the determination of DA in spiked
      artificial urine samples, where it gave recoveries ranging from 97.6 to 102.2%,
      demonstrating that the method a promising tool for rapid and selective detection
      of DA. Graphical abstract MoS2 QDs are facilely synthesized via the etching
      effect of ammonium hydroxide for highly selective fluorometric detection of
      dopamine.

PMID- 29594719
TI  - Decreased activity of RCAN1.4 is a potential risk factor for congenital heart
      disease in a Han Chinese population.

PMID- 29594718
TI  - Suicidality in Subjects With Anxiety or Obsessive-Compulsive and Related
      Disorders: Recent Advances.
AB  - PURPOSE OF REVIEW: Historically, anxiety disorders have not been considered as
      important determinants of suicide, but in the last years, many works have
      challenged this assumption. Here, we will review the available evidence on the
      relationship between suicide and anxiety disorders (e.g., obsessive-compulsive
      disorder, post-traumatic stress disorder, generalized anxiety disorder, panic
      disorder, and body dysmorphic disorder), with special emphasis on findings
      published in the last years. RECENT FINDINGS: Overall, anxiety disorders increase
      the risk of suicide. Specifically, 16% of patients with social anxiety disorder
      reported suicidal ideation in the previous month, and 18% of them had a history
      of suicide attempts. Similarly, in patients with panic disorder, suicidal
      ideation prevalence ranged between 17 and 32%, and 33% of them had a history of
      suicide attempts. Generalized anxiety disorder (GAD) was the most frequent
      anxiety disorder in completed suicides (present in 3% of people who committed
      suicide) and also subthreshold GAD was clearly linked to suicide ideation. Post
      traumatic stress disorder was positively associated with suicidal ideation, and
      in patients with obsessive-compulsive disorder, suicide ideation rates ranged
      from 10 to 53% and suicide attempts from 1 to 46%. Body dysmorphic disorders
      presented a suicide ideation prevalence of about 80%. Suicide risk is increased
      in subjects with anxiety disorder. This risk is higher in the presence of
      comorbidities, but it is not clear whether it is independent from such
      comorbidities in some disorders.

PMID- 29594720
TI  - Ligand binding and conformational changes of SUR1 subunit in pancreatic ATP
      sensitive potassium channels.
AB  - ATP-sensitive potassium channels (KATP) are energy sensors on the plasma
      membrane. By sensing the intracellular ADP/ATP ratio of beta-cells, pancreatic
      KATP channels control insulin release and regulate metabolism at the whole body
      level. They are implicated in many metabolic disorders and diseases and are
      therefore important drug targets. Here, we present three structures of pancreatic
      KATP channels solved by cryo-electron microscopy (cryo-EM), at resolutions
      ranging from 4.1 to 4.5 A. These structures depict the binding site of the
      antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium
      channel 6.2) N-terminus participates in the coupling between the peripheral SUR1
      (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the
      binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP
      binding on nucleotide binding domains (NBDs) drives a conformational change of
      the SUR1 subunit.

PMID- 29594721
TI  - 3D nitrogen-doped graphite foam@Prussian blue: an electrochemical sensing
      platform for highly sensitive determination of H2O2 and glucose.
AB  - A platform is described for voltammetric sensing of hydrogen peroxide (H2O2). It
      is based on the use of nitrogen-doped graphite foam modified with Prussian Blue
      particles (PB/NGF). Graphite foam was synthesized by chemical vapor deposition,
      and doping with nitrogen was realized via dielectric barrier plasma discharge. PB
      particles were grown on the NGF through electrodeposition. SEM images of NGF
      verified the porous and interconnected structure of graphite foam, and XPS and
      Raman spectroscopy verified the successful doping with N. The performance of the
      PB/NGF electrode was characterized by CV and EIS which showed it to possess
      outstanding properties in terms of sensing H2O2. H2O2 was quantified in a range
      of 0.004 to 1.6 mM with a detection limit of 2.4 MUM. The PB/NGF electrode also
      is shown to be a viable substrate for loading glucose oxidase (GOx). The GOx
      functionalized electrode responds to glucose over the 0.2 to 20 mM concentration
      range at a potential of -50 mV (vs. Ag/AgCl), with a sensitivity of 27.48 mA M-1
      cm-2 and a 0.1 M detection limit (at an S/N ratio of 3). The glucose sensor is
      selective, stable, and reproducible. The biosensor was successfully applied to
      the determination of glucose in spiked human serum samples, and this confirmed it
      practicability. Graphical abstract Schematic of a self-supporting amperometric
      glucose biosensor based on glucose oxidase and Prussian blue modified 3D nitrogen
      doped graphite foam.

PMID- 29594722
TI  - Unclaimed Prize Information Biases Perceptions of Winning in Scratch Card
      Gambling.
AB  - Unclaimed prize information (i.e., the number of prizes still available to be
      won) is information commonly provided to scratch card gamblers. However, unless
      the number of tickets remaining to be purchased is also provided, this
      information is uninformative. Despite its lack of utility in assisting gamblers
      in choosing the most favourable type of scratch card to play, we hypothesized
      that unclaimed prize information would bias participants' judgments within a
      scratch card gambling context. In Experiment 1 (N = 201), we showed that
      participants are influenced by this information such that they felt more likely
      to win, were more excited to play, and preferred to hypothetically purchase more
      of the scratch card with the greatest number of unclaimed prizes. In Experiment 2
      (N = 201), we attempted to ameliorate this bias by providing participants with
      the number of tickets remaining to be purchased and equating the payback
      percentages of all three games. The bias, although attenuated, still persisted in
      these conditions. Finally, in Experiment 3 (N = 200), we manipulated the
      hypothetical scratch cards such that games with the highest number of unclaimed
      prizes were the least favourable, and vice versa. As in Experiment 2,
      participants still favoured cards with greater numbers of unclaimed prizes.
      Possible mechanisms underlying this bias are discussed. In conclusion, across
      three experiments, we demonstrate that salient unclaimed prize information is
      capable of exerting a strong effect over judgments related to scratch card games.

PMID- 29594723
TI  - How do children with and without ADHD talk about frustration?: Use of a novel
      emotion narrative recall task.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) experience
      difficulties related to emotional reactivity and regulation. The current study
      examines differences in the emotional reactivity and regulation of children with
      and without ADHD in the context of their real-life experiences of negative
      emotion using a novel ecologically valid methodology. Eighty-three 8-12-year-old
      children (46 ADHD, 38 non-ADHD) participated in the study. Children completed the
      negative emotion narrative recall task, a novel task whereby children provided a
      narrative recall of a real-life event where they experienced negative emotion.
      ANCOVA indicated children with ADHD recalled significantly more overall
      frustration and intense frustration than children without ADHD. Children with
      ADHD exhibiting more negative emotional reactivity while recalling negative
      emotions than children without ADHD. The current study suggests that children
      with ADHD are uniquely impacted by negative emotional experiences and represents
      an important step in understanding the emotional reactivity and regulation of
      children with ADHD.

PMID- 29594724
TI  - Kinetics of liver regeneration in donors after living donor liver
      transplantation: A retrospective analysis of "2/3rd partial hepatectomy" model at
      3 months.
AB  - BACKGROUND/AIM: Right lobe living donor (2/3rd partial hepatectomy) model is the
      best way to accurately study liver regeneration process in human beings. We aimed
      to study the kinetics of liver regeneration after 2/3rd partial hepatectomy in
      donors. METHODS: Retrospective analysis of prospectively maintained volumetric
      recovery data in donors was performed in 23 donors, who underwent 29 contrast
      enhanced computed tomography within 3 months for various clinical indications.
      RESULTS: The absolute volumetric growth percentages were as follows: 37.60 +/-
      21.74 at 1st week, 92 +/- 53.27 at 2nd week, 115.55 +/- 59.65 at 4th week, and
      110.79 +/- 64.47 at 3 months. On sub-group analysis of our cohort, we found that
      4.3%, 17%, 30.4%, and 39% donors attended >= 90% volumetric recovery at 1st, 2nd,
      4th week, and 3 months, respectively. One patient at 4th week revealed 128%
      volumetric recovery. There was one more patient who exceeded original total liver
      volumes (TLV) (111% of TLV) at 2.5 months. The serum bilirubin and INR values
      peaked at postoperative day (POD) 3rd and then started showing a downward trend
      from POD 5th onwards. CONCLUSION: Our study is the first to document complete
      volumetric recovery in donors as early as 3 weeks. Two of the donors overshot
      their original TLV during the early regenerative phase.

PMID- 29594725
TI  - Graphene oxide-based fluorometric determination of methicillin-resistant
      Staphylococcus aureus by using target-triggered chain reaction and
      deoxyribonuclease-assisted recycling.
AB  - The authors describe a method for the fluorometric determination of methicillin
      resistant Staphylococcus aureus (MRSA) by exploiting target-triggered chain
      reactions and deoxyribonuclease I (DNase I)-aided target recycling. It is making
      use of a carboxy-fluorescein (FAM)-labeled single-stranded probe containing two
      sections. One is complementary to the 5' terminus of the target, while the 3'
      terminus of the other target is adsorbed on the surface of graphene oxide (GO)
      via pi-stacking interactions without the target (16S rRNA). This adsorption
      results in quenching of the fluorescence of the label and protects it from being
      cleaved by DNase I. However, upon addition of the target, DNA/RNA hybrids are
      repelled by GO. This leads to fluorescence recovery as measured at
      excitation/emission wavelengths of 480/514 nm due to a chain reaction that is
      triggered by the target. The signal is strongly amplified by using DNase I
      mediated target recycling. The 16S rRNA of MRSA can be detected by this method in
      the 1 to 30 nM concentration range, and the detection limit is 0.02 nM. The
      method was applied to analyze bacterial samples, and the detection limit is as
      low as 30 CFU . mL-1. The assay is highly sensitive and selective and in our
      percpetion has a large potential in diagnosis of drug-resistant bacteria.
      Graphical abstract Schematic of the graphene oxide-based fluorescent bioassay for
      Methicillin-resistant Staphylococcus aureus detection by using target-triggered
      chain reaction and deoxyribonuclease I-aided signal amplification.

PMID- 29594726
TI  - Modified Global Flower Pollination Algorithm and its Application for Optimization
      Problems.
AB  - Flower Pollination Algorithm (FPA) has increasingly attracted researchers'
      attention in the computational intelligence field. This is due to its simplicity
      and efficiency in searching for global optimality of many optimization problems.
      However, there is a possibility to enhance its search performance further. This
      paper aspires to develop a new FPA variant that aims to improve the convergence
      rate and solution quality, which will be called modified global FPA (mgFPA). The
      mgFPA is designed to better utilize features of existing solutions through
      extracting its characteristics, and direct the exploration process towards
      specific search areas. Several continuous optimization problems were used to
      investigate the positive impact of the proposed algorithm. The eligibility of
      mgFPA was also validated on real optimization problems, where it trains
      artificial neural networks to perform pattern classification. Computational
      results show that the proposed algorithm provides satisfactory performance in
      terms of finding better solutions compared to six state-of-the-art optimization
      algorithms that had been used for benchmarking.

PMID- 29594727
TI  - Circular exponential amplification of photoinduced electron transfer using
      hairpin probes, G-quadruplex DNAzyme and silver nanocluster-labeled DNA for
      ultrasensitive fluorometric determination of pathogenic bacteria.
AB  - The authors describe a fluorometric strategy for the detection of pathogenic
      bacteria with ultrasensitivity and high specificity. This strategy relies on the
      combination of target-modulated photoinduced electron transfer (PET) between G
      quadruplex DNAzyme and DNA (labeled with silver nanoclusters) along with hairpin
      probe-based circular exponential amplification. The reaction system involves
      three hairpin probes (H1, H2 and H3). Probe H1 contains an aptamer against S.
      Typhimurium and the recognition sequence for nicking endonuclease. It is used to
      recognize S. Typhimurium and participates in polymerase-catalyzed target recycle
      amplification and secondary-target recycle amplification. Probe H2 contains an
      aptamer against hemin and is used to form the G-quadruplex DNAzyme in the
      presence of hemin and potassium ion. It acts as the electron acceptor and
      quenches the fluorescence of the labeled DNA. Fluorescence is best measured at
      excitation/emission wavelengths of 567/650 nm. Probe H3 contains the template
      sequence for the synthesis of AgNCs and the H2-annealing sequence. Both H2 and H3
      are utilized to perform a strand displacement reaction and to achieve PET between
      G-quadruplex DNAzyme and DNA/AgNCs. To the best of our knowledge, this is the
      first example of a PET between G-quadruplex DNAzyme and DNA/AgNCs coupled with
      circular exponential amplification. The assay has an ultra-low detection limit 8
      cfu.mL-1 of S. Typhimurium. The assay is rapid, accurate, inexpensive and simple.
      Hence, the strategy may represent a useful platform for ultrasensitive and highly
      specific detection of pathogenic bacteria as encountered in food analysis and
      clinical diagnosis. Graphical abstract The reaction system includes three hairpin
      probes (H1, H2 and H3), primer probe (P), Phi 29 DNA ploymerase (Phi 29) and
      nicking endonuclease Nt.AlwI (Nt.AlwI). Phi 29 and Nt.AlwI -assisted signal
      amplification leads to the recycling of target and produces numerous single
      stranded-DNAs (S). Strand displacement amplification leads to photoinduced
      electron transfer (PET) between G-quadruplex DNAzyme and DNA/AgNCs. HAP-based
      circular exponential amplification of PET results in an ultrasensitive
      fluorometric assay.

PMID- 29594728
TI  - Effect of silica surface coating on the luminescence lifetime and upconversion
      temperature sensing properties of semiconductor zinc oxide doped with
      gallium(III) and sensitized with rare earth ions Yb(III) and Tm(III).
AB  - Optical sensing of temperature by measurement of the ratio of the intensities of
      the 700 nm emission and the 800 nm emission of Ga(III)-doped ZnO (GZO)
      nanoparticles (NPs) and of GZO NPs coated with a silica shell are demonstrated at
      980 nm excitation. It is found that the relative sensitivity of SiO2@Yb/Tm/GZO is
      6.2% K-1 at a temperature of 693 K. This is ~3.4 times higher than that of
      Yb/Tm/GZO NPs. Obviously, the SiO2 shell structure decreases the rate of the
      nonradiative decay. The decay time of the 800 nm emission of the Yb/Tm/GZO NPs
      (15 mol% Ga; 7 mol% Yb; 0.5 mol% Tm) displays a biexponential decay with a
      dominant decay time of 148 MUs and a second decay time of ~412 MUs. The lifetime
      of the Yb/Tm/GZO NPs at 293 K, and of the SiO2@Yb/Tm/GZO NPs are ~412 MUs. Both
      the Yb/Tm/GZO and SiO2@Yb/Tm/GZO can be used up to 693 K. These results indicate
      that the SiO2 shell on the Yb/Tm/GZO is beneficial in terms of sensitivity and
      resolution. Graphical abstract The enhancement the decay time and thermal
      sensitivity in the SiO2@Yb/Tm/GZO shell@core structure have been studied compared
      to the Ga(III)-doped Yb/Tm-doped ZnO (Yb/Tm/GZO). The SiO2@Yb/Tm/GZO have good
      thermal accuracy up to 693  degrees C.

PMID- 29594729
TI  - A nanocomposite consisting of MIL-101(Cr) and functionalized magnetite
      nanoparticles for extraction and determination of selenium(IV) and selenium(VI).
AB  - A metal-organic framework nanocomposite was synthesized and applied to speciation
      analysis of Se(IV) and Se(VI). The sorbent is composed of MIL-101(Cr) and
      magnetite nanoparticles modified with dithiocarbamate. It is capably of
      selectively extracting Se(IV) at pH = 1.85, while Se(VI) remains in solution. The
      total amount of selenium can then be determined by reducing Se(VI) to Se(IV) and
      also extracting it. The extraction parameters were optimized by employing design
      of-experiments methodology. Selenium was then quantified by electrothermal AAS.
      Figures of merit include (a) a 10 ng.L-1 limit of detection, (b) a linear
      response in the 30 ng.L-1 to 10 MUg.L-1 concentration range, and (a) a relative
      standard deviation of <11.5% for Se(IV). The method was validated by analyzing
      certified reference materials (water and tomato leaves). It was also applied to
      the speciation analysis of Se(IV) and Se(VI) in (spiked) water samples and of
      total selenium in agricultural samples. Graphical abstract Schematic of the
      synthesis of a metal-organic framework nanocomposite for speciation analysis of
      Se(IV) and Se(VI). The sorbent is composed of MIL-101(Cr) and magnetite
      nanoparticles modified with dithiocarbamate. Selenium can be quantified by
      electrothermal AAS with a 10 ng L-1 detection limit.

PMID- 29594730
TI  - Fluorometric determination of nucleic acids based on the use of polydopamine
      nanotubes and target-induced strand displacement amplification.
AB  - The authors describe a fluorometric method for the quantitation of nucleic acids
      by combining (a) cycled strand displacement amplification, (b) the unique
      features of the DNA probe SYBR Green, and (c) polydopamine nanotubes. SYBR Green
      undergoes strong fluorescence enhancement upon intercalation into double-stranded
      DNA (dsDNA). The polydopamine nanotubes selectively adsorb single-stranded DNA
      (ssDNA) and molecular beacons. In the absence of target DNA, the molecular
      beacon, primer and SYBR Green are adsorbed on the surface of polydopamine
      nanotubes. This results in quenching of the fluorescence of SYBR Green, typically
      measured at excitation/emission wavelengths of 488/518 nm. Upon addition of
      analyte (target DNA) and polymerase, the stem of the molecular beacon is opened
      so that it can bind to the primer. This triggers target strand displacement
      polymerization, during which dsDNA is synthesized. The hybridized target is then
      displaced due to the strand displacement activity of the polymerase. The
      displaced target hybridizes with another molecular beacon. This triggers the next
      round of polymerization. Consequently, a large amount of dsDNA is formed which is
      detected by addition of SYBR Green. Thus, sensitive and selective fluorometric
      detection is realized. The fluorescent sensing strategy shows very good
      analytical performances towards DNA detection, such as a wide linear range from
      0.05 to 25 nM with a low limit of detection of 20 pM. Graphical abstract
      Schematic of a fluorometric strategy for highly sensitive and selective
      determination of nucleic acids by combining strand displacement amplification and
      the unique features of SYBR Green I (SG) and polydopamine nanotubes.

PMID- 29594731
TI  - Carbon quantum dot-based fluorometric nitrite assay by exploiting the oxidation
      of iron(II) to iron(III).
AB  - The authors describe a simple and economical fluorescence method for the
      determination of nitrite by utilizing the fact that nitrite possesses strong
      oxidation in acidic solution and is capable to transform iron(II) into iron(III)
      ions. The latter quenches the fluorescence of carbon quantum dots (CQDs) based on
      the fluorescence static and dynamic quenching effect. The optimum reaction
      conditions and other analytical parameters are investigated to enhance the
      sensitivity of the method. At the excitation wavelength of 360 nm, this probe has
      a linear response in the 10 to 400 MUM nitrite concentration range, with a
      correlation coefficient of R2 = 0.9958 (n = 3) and a detection limit of 0.48 MUM.
      This method was successfully applied to the determination of nitrite in three
      different sausage samples and gave recoveries in the range between 101.8 to
      103.0%, demonstrating the accuracy, reliability and potential application of this
      assay for monitoring nitrite. Graphical Abstract The carbon quantum dot/iron(II)
      ions system was used for the fluorometric detection of nitrite in food and
      environmental water. This probe exploits the oxidizing property of nitrite in
      acidic solution. Iron(II) is oxidized to iron(III) which exerts a strong
      fluorescence quenching effect.

PMID- 29594732
TI  - Lycium barbarum Polysaccharide Promotes Nigrostriatal Dopamine Function by
      Modulating PTEN/AKT/mTOR Pathway in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) Murine Model of Parkinson's Disease.
AB  - To investigate the effects of Lycium barbarum polysaccharide (LBP) on
      pathological symptoms and behavioral deficits in a Methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. The
      therapeutic effects of LBP were monitored with an Open field test, a Rotarod test
      and a Morris water maze test. We also investigated the mechanisms with qRT-PCR
      and Western blotting analyses. After a relatively short-term LBP treatment, the
      total distance and walking time of PD mice significantly increased. The staying
      duration on the rod of PD mice increased in the Rotarod test. LBP can up-regulate
      levels of SOD2, CAT and GPX1 and inhibit the abnormal aggregation of alpha
      synuclein induced by MPTP. LBP treatment can also up-regulate the phosphorylation
      of AKT and mTOR, and may play its protective role by activating the PTEN/AKT/mTOR
      signaling axis. These results suggest that LBP can effectively alleviate the
      degeneration in the nigrostriatal system induced by MPTP treatment. It may be a
      potential candidate for the treatment of Parkinson's disease.

PMID- 29594733
TI  - Fast evaluation of protein dynamics from deficient 15N relaxation data.
AB  - Simple and convenient method of protein dynamics evaluation from the insufficient
      experimental 15N relaxation data is presented basing on the ratios, products, and
      differences of longitudinal and transverse 15N relaxation rates obtained at a
      single magnetic field. Firstly, the proposed approach allows evaluating overall
      tumbling correlation time (nanosecond time scale). Next, local parameters of the
      model-free approach characterizing local mobility of backbone amide N-H vectors
      on two different time scales, S2 and R ex , can be elucidated. The generalized
      order parameter, S2, describes motions on the time scale faster than the overall
      tumbling correlation time (pico- to nanoseconds), while the chemical exchange
      term, R ex , identifies processes slower than the overall tumbling correlation
      time (micro- to milliseconds). Advantages and disadvantages of different methods
      of data handling are thoroughly discussed.

PMID- 29594734
TI  - Voltammetric determination of attomolar levels of a sequence derived from the
      genom of hepatitis B virus by using molecular beacon mediated circular strand
      displacement and rolling circle amplification.
AB  - The authors describe an electrochemical method for the determination of the
      single-stranded DNA (ssDNA) oligonucleotide with a sequence derived from the
      genom of hepatitis B virus (HBV). It is making use of circular strand
      displacement (CSD) and rolling circle amplification (RCA) strategies mediated by
      a molecular beacon (MB). This ssDNA hybridizes with the loop portion of the MB
      immobilized on the surface of a gold electrode, while primer DNA also hybridizes
      with the rest of partial DNA sequences of MB. This triggers the MB-mediated CSD.
      The RCA is then initiated to produce a long DNA strand with multiple tandem
      repeat sequences, and this results in a significant increase of the differential
      pulse voltammetric response of the electrochemical probe Methylene Blue at a
      rather low working potential of -0.24 V (vs. Ag/AgCl). Under optimal experimental
      conditions, the assay displays an ultrahigh sensitivity (with a 2.6 aM detection
      limit) and excellent selectivity. Response is linear in the 10 to 700 aM DNA
      concentration range. Graphical abstract Schematic of a voltammetric method for
      the determination of attomolar levels of target DNA. It is based on molecular
      beacon mediated circular strand displacement and rolling circle amplification
      strategies. Under optimal experimental conditions, the assay displays an
      ultrahigh sensitivity with a 2.6 aM detection limit and excellent selectivity.

PMID- 29594735
TI  - Polydopamine nanodots are viable probes for fluorometric determination of the
      activity of alkaline phosphatase via the in situ regulation of a redox reaction
      triggered by the enzyme.
AB  - The authors describe an environmentally friendly and fast (~14 min) method for
      the synthesis of homogeneously distributed fluorescent polydopamine nanodots (PDA
      NDs) using KMnO4 as the oxidant. Alkaline phosphatase (ALP) catalyzes the
      hydrolysis of ascorbic acid 2-phosphate to release free ascorbic acid which
      undergoes an in-situ redox reaction with KMnO4. Depending on the activity of ALP,
      more or less KMnO4 is consumed, and this affects the formation of the PDA-NDs.
      Based on this finding, a sensitive method was worked out to quantify the activity
      of ALP via real-time formation of fluorescent PDA-NDs. The fluorometric signal
      (best measured at excitation/emission peaks of 390/500 nm) is linear in the 1 to
      50 mU.mL-1 ALP activity range, and the limit of the detection is as low as 0.94
      mU.mL-1 (based on 3 sigma/m). The method was successfully applied to the
      determination of ALP activity in spiked human serum and in MCF-7 cell lysates. It
      was also applied in a method to screen for inhibitors of ALP. Graphical abstract
      Schematic of a fluorometric method for the determination of alkaline phosphatase
      (ALP) activity. The method is based on the in-situ regulation of the formation of
      fluorescent polydopamine nanodots (PDA-NDs) through the competition between the
      KMnO4-induced polymerization of dopamine and ALP-directed ascorbic acid 2
      phosphate (Asc-2P) hydrolysis. AA: Ascorbic acid.

PMID- 29594736
TI  - Gold nanorods for in-drop colorimetric determination of thiomersal after
      photochemical decomposition.
AB  - This work reports on the implementation of gold nanorods (AuNRs) in headspace
      solvent microextraction for colorimetric determination of volatile analyte
      derivatives in a single drop. The exposure of AuNRs to both H2Se and elemental
      mercury (Hg0) results in a shift of the longitudinal plasmonic band, unlike a
      number of volatiles. Accordingly, a method is reported for the determination of
      Hg0 with potential applicability to the determination of thiomersal (sodium
      ethylmercurithiosalicylate). It is based on the photochemical decomposition of
      thiomersal into Hg(II) and subsequent exposure of AuNRs-containing microdrop to
      in situ generated Hg0. Colorimetric analysis of the enriched drop was carried out
      without dilution by means of a cuvetteless microvolume UV-vis spectrometer. Under
      optimal conditions, the limit of detection was 0.5 ng mL-1 (as Hg). The
      repeatability, expressed as relative standard deviation, was 8.4% (for n = 10).
      AuNRs exposed to increasing concentrations of the analyte were characterized by
      means of transmission electron microscopy and UV-vis spectrophotometry to
      ascertain the mechanism of detection. The method was finally applied to the
      determination of thiomersal in various pharmaceutical samples and showed
      quantitative recoveries. Graphical abstract Schematic illustration of a
      miniaturized colorimetric method based on the use of a microdrop of gold nanorods
      (AuNRs) for thiomersal determination in pharmaceuticals. It is based on the
      photochemical decomposition of thiomersal and subsequent Hg0 generation with in
      drop amalgamation.

PMID- 29594737
TI  - Glomuvenous malformations: dual PDL-Nd:YAG laser approach.
AB  - Glomuvenous malformations are uncommon simple vascular malformations that might
      be present at birth or appear during childhood that have been classically
      classified as a subtype of venous malformations. Sclerotherapy and surgery have
      been used in the past as treatments for this condition although with
      disappointing results in large glomangiomas. The treatment of these lesions has
      still not been standardized. We conducted a retrospective study of 17 patients
      treated with dual wavelength PDL-Nd:YAG. The majority of the patients experience
      a reduction of at least a 60% in their glomuvenous malformations. Treatment was
      well-tolerated, and adverse effects were rare.

PMID- 29594738
TI  - A gold nanoparticle based fluorescent probe for simultaneous recognition of
      single-stranded DNA and double-stranded DNA.
AB  - A fluorescent method is described for simultaneous recognition of single-stranded
      DNA (ssDNA) and double-stranded DNA (dsDNA). It is based on the quenching of the
      fluorescence of fluorophore labeled DNA probes by gold nanoparticles (AuNPs). To
      demonstrate feasibility, two DNA probes labeled with spectrally different
      fluorophores were designed. The first DNA probe (P1) was modified with 6
      carboxyfluorescein (FAM; with green fluorescence, peaking at 518 nm), while the
      second (P2) was modified with carboxy-X-rhodamine (ROX; with yellow fluorescence,
      610 nm). The fluorescence signals of the labels are quenched if P1 or P2 are
      adsorbed on AuNPs. Upon addition of ssDNA and dsDNA, hybridization occurs between
      P1 and ssDNA to form a dsDNA. In contrast, P2 hybridizes with dsDNA such that a
      triplex DNA is formed. As a result, the dsDNA and the triplex DNA, respectively,
      are desorbed from the surface of the AuNPs so that quenching no longer can occur
      and strong fluorescence can be observed. Under the optimal conditions, ssDNA and
      dsDNA can be detected simultaneously via the green and yellow fluorescence,
      respectively. The detection limits can be as low as 330 pM. In particular, the
      method has excellent selectivity for the target DNAs over control DNAs. Graphical
      abstract A gold nanoparticle based fluorescent probe for simultaneous recognition
      of single-stranded DNA and double-stranded DNA is developed based on the
      fluorescence quenching of gold nanoparticles to different fluorophore labeled DNA
      probes.

PMID- 29594741
TI  - Psychological Determinants of Attitude Toward Euthanasia: A Comparative Study of
      Female Nurses and Female Nonmedical Professionals.
AB  - Moral, legal, and psychological aspects of the legality of euthanasia are subject
      to debates and studies of various communities. Diagnosing attitudes toward
      euthanasia should involve not only determining the proportion between its
      supporters and opponents but also the describing of mechanisms behind the
      development of particular views. The aim of the present study was to determine
      the psychological determinants of attitudes, such as fear of death-dying, self
      esteem, and mood. The methods consisted of using the following questionnaires:
      the Glebocka-Gawor Attitudes Toward Euthanasia Inventory, the Ochsmann Fear of
      Death and Dying Inventory, the Dymkowski Self-Description Scale, the Adamczyk
      Glebocka Negative Mood Inventory, and a measure of unconscious fear of death. The
      study involved 49 female nurses and 43 female nonmedical professionals. The
      results demonstrate that the attitudes and fear of death-dying did not
      differentiate the two groups of participants. Although the fear of dying weakened
      the strength of conservative views, it also reinforced the need for informational
      and psychological support. A high self-esteem was a predictor of conservative
      attitudes, while negative mood predicted liberal attitudes. Conservative
      attitudes were connected to a hidden fear of death and high self-esteem, while
      liberal attitudes were linked to a conscious fear and a rational vision of the
      self, the world, and the future.

PMID- 29594739
TI  - The IBD and PSC Phenotypes of PSC-IBD.
AB  - PURPOSE OF REVIEW: To review the characteristics of IBD and PSC that occur in
      association, as well as their reciprocal influences on disease evolution, in
      adult and pediatric populations. RECENT FINDINGS: IBD co-existing with PSC is
      genetically and clinically distinct from IBD alone. It is frequently
      characterized by pancolitis, rectal sparing, and possibly backwash ileitis, as
      well as a threefold increased risk of colorectal dysplasia. Adults and children
      with colitis and PSC appear to be at increased risk of active endoscopic and
      histologic disease in the absence of symptoms compared to individuals without
      PSC. PSC occurring with Crohn's disease has been observed to be less severe than
      PSC co-existing with ulcerative colitis, independent of its association with
      small duct disease. Recent studies suggest that colectomy is associated with a
      decreased risk of recurrent PSC after liver transplantation, challenging the
      traditional teaching that PSC and IBD evolve independently. While much about the
      gut-liver axis in PSC-IBD remains poorly understood, the IBD associated with PSC
      has a unique phenotype, of which subclinical inflammation is an important
      component. Additional research is needed to characterize further the potentially
      protective role of colectomy against recurrent PSC post-liver transplantation and
      to investigate the influence of IBD control and/or colectomy on PSC progression.

PMID- 29594740
TI  - Photodynamic therapy of balloon-injured rat carotid arteries using indocyanine
      green.
AB  - Photodynamic therapy (PDT) has been used to inhibit intimal hyperplasia in
      injured arteries. Because of the limited tissue penetration of visible light, an
      endovascular light source with a guided wire is often required for effective
      treatment. Indocyanine green (ICG), a near-infrared (NIR) photosensitizer, has
      been used in PDT for cancers. An extracorporeal light source may be used for
      shallow tissue because of the better tissue penetration of NIR light. The aim of
      this study was to evaluate the effect of ICG-PDT using extracorporeal NIR light
      on the inhibition of intimal hyperplasia in balloon-injured carotid arteries. A
      balloon injury (BI) model was used to induce intimal hyperplasia of carotid
      artery. Sprague-Dawley rats were divided into control, BI, BI + 1 * PDT, and BI +
      2 * PDT groups. The control group underwent a sham procedure. PDT was performed 7
      days after BI. In the BI + 1 * PDT group, ICG was administered 1 h before light
      irradiation. External illumination with 780-nm light-emitting diode light at a
      fluence of 4 J/cm2 was applied. For the BI + 2 * PDT group, PDT was performed
      again at day 7, following the first PDT. Hematoxylin and eosin (H & E) staining
      was performed to assess vessel morphology. Arterial wall thickness was
      significantly larger in the BI group compared with the control group. ICG-PDT
      significantly reduced arterial wall thickness compared with the BI group.
      Repeated PDT further decreased arterial wall thickness to the level of the
      control group. These findings indicate a promising approach for the treatment of
      restenosis of carotid arteries.

PMID- 29594742
TI  - Taylor-Green vortex simulation using CABARET scheme in a weakly compressible
      formulation.
AB  - In present paper we recall the canonical Taylor-Green vortex problem solved by in
      house implementation of the novel CABARET numerical scheme in weakly compressible
      formulation. The simulations were carried out on the sequence of refined grids
      with [Formula: see text], [Formula: see text], [Formula: see text] cells at
      various Reynolds numbers corresponding to both laminar ([Formula: see text]) and
      turbulent ([Formula: see text]) vortex decay scenarios. The features of the
      numerical method are discussed in terms of the kinetic energy dissipation rate
      and integral enstrophy curves, temporal evolution of the spanwise vorticity,
      energy spectra and spatial correlation functions.

PMID- 29594743
TI  - A glassy carbon electrode modified with cerium phosphate nanotubes for the
      simultaneous determination of hydroquinone, catechol and resorcinol.
AB  - A nafion film containing cerium phosphate nanotubes was pasted onto a glassy
      carbon electrode (GCE) to obtain a sensor for hydroquinone (HQ). The morphologies
      and components of the coating were characterized by transmission electron
      microscopy, scanning electron microscopy and energy-dispersive spectroscopy.
      Cyclic voltammetry and differential pulse voltammetry (DPV) showed the specific
      surface of the electrode to be significantly increased and the electron transfer
      rate to be accelerated. The modified GCE was applied to the determination of
      hydroquinone (HQ) via DPV. The oxidation current increases linearly in the 0.23
      MUM to 16 mM HQ concentration range which is as wide as five orders of magnitude.
      The limit of detection is 0.12 MUM (based on a signal-to-noise ratio of 3), and
      the sensitivity is 1.41 MUA.MUM-1 cm-2. The method was further applied to the
      simultaneous determination of HQ, catechol and resorcinol. The potentials for the
      three species are well separated (20, 134, and 572 mV vs SCE). Average recoveries
      from (spiked) real water samples are between 95.2 and 107.0%, with relative
      standard deviations of 0.9~2.7% (for n = 3) at three spiking levels. The method
      was validated by independent assays using HPLC. Graphical abstract ?.

PMID- 29594744
TI  - Amperometric determination of myo-inositol by using a glassy carbon electrode
      modified with molecularly imprinted polypyrrole, reduced graphene oxide and
      nickel nanoparticles.
AB  - This paper reports on the development of an amperometric method for the
      determination of myo-inositol. The method involves coating of a glassy carbon
      electrode (GCE) with a molecularly imprinted polymer (MIP) and reduced graphene
      oxide (RGO) that was modified with nickel nanoparticles (NiNPs). The MIP was
      prepared by electropolymerization of pyrrole on the surface of the GCE in the
      presence of myo-inositol molecules. The construction steps of the modified
      electrode were monitored via cyclic voltammetry, atomic force microscopy,
      scanning electron microscopy and X-ray Photoelectron Spectroscopy. The results
      were evaluated using differential pulse voltammetry, in which hexacyanoferrate
      was used as an electrochemically active probe. Under optimized experimental
      conditions, the imprint-modified GCE has a linear response in the 1.0 * 10-10 mol
      L-1 to 1.0 * 10-8 mol L-1 concentration range, with a 7.6 * 10-11 mol L-1
      detection limit and an electrochemical sensitivity of 4.5 MUA.cm-2 MUmol-1. The
      method showed improved selectivity even in the presence of molecules with similar
      chemical structure. The GCE modified was successfully applied to the
      determination of myo-inositol in sugarcane vinasse where it yielded recoveries
      that ranged from 95 to 102%. Graphical abstract Schematic presentation of
      molecularly imprinted polymer (MIP) on a glassy carbon electrode (GCE) modified
      with nickel nanoparticles (NiNP) anchored in reduced graphene oxide (RGO). The
      resulting MIP/NiNP/RGO-GCE was used for indirect determination of myo-inositol.

PMID- 29594745
TI  - Three kinds of lateral flow immunochromatographic assays based on the use of
      nanoparticle labels for fluorometric determination of zearalenone.
AB  - Colloidal gold, quantum dots and polystyrene microspheres were used as labels in
      three kinds of lateral flow immunochromatographic assays (ICAs) for the detection
      of zearalenone (ZEN) in cereal samples. The assays allow ZEN to be quantified
      within 20 min. The LODs are 10 MUg.L-1 of ZEN for the colloidal gold-based ICA,
      and 1 MUg.L-1 for both the quantum dot and polystyrene microsphere based ICAs.
      The respective data are 60 MUg.kg-1, 6 MUg.kg-1 and 6 MUg.kg-1, respectively, for
      spiked samples and cereals. Only minor cross-sensitivity occurred between ZEN and
      fusarium toxins, and no cross-sensitivity if found for aflatoxin B1, T-2
      mycotoxin, ochratoxin A, deoxynivalenol, and fumonisin B1. LODs of the three
      assays are lower than the maximum limits of ZEN set by most standardization
      agencies. Graphical abstract Schematic presentation of three lateral flow
      immunochromatographic assays (ICAs) based on the use of (a) colloidal gold (CG),
      (b) fluorescent quantum dots (QD), and

PMID- 29594746
TI  - Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and
      Future.
AB  - PURPOSE OF REVIEW: Universal stool banks (USBs) have emerged as a potential model
      for scaling access to fecal microbiota transplantation (FMT) for Clostridium
      difficile infection (CDI). In this review, we outline the historical barriers
      constraining access to FMT, the evidence on methods and outcomes of USBs, and
      potential future directions for expanding access. RECENT FINDINGS: Key historical
      barriers to FMT access include regulatory uncertainty, operational complexity of
      sourcing screened donor material, and logistical challenges of delivering fresh
      treatment preparations. USBs have demonstrated that FMT can be delivered safely
      at scale by centralizing donor selection, material processing, and safety
      monitoring. More evidence is needed to optimize USB methods, including for donor
      screening, material processing, and novel delivery modalities. USBs have
      catalyzed broad access to FMT in North America and Europe. Future directions
      include developing evidence regarding oral preparations, harmonizing guidelines,
      disseminating best practice protocols, establishing long-term safety profiles,
      and expanding access to geographic areas of unmet need.

PMID- 29594747
TI  - Pelvic floor function following ventral rectopexy versus STARR in the treatment
      of obstructed defecation.
AB  - BACKGROUND: Obstructed defecation syndrome (ODS), most commonly found in females,
      can be treated by a transanal or abdominal approach with good success rate.
      Nevertheless, patients may experience de novo or persisting pelvic floor
      dysfunctions after surgery. The aim of this study was to compare the functional
      outcome of stapled transanal rectal resection (STARR) and ventral rectopexy (VRP)
      in a series of ODS patients. METHODS: Forty-nine female patients who had surgery
      for ODS between 2006 and 2016 were retrospectively evaluated: 28 (median age 60
      years, IQR 54-69 years) had VRP and 21 (median age 58 years, IQR 51-66 years) had
      STARR. ODS was scored with the ODS score while the overall pelvic floor function
      was assessed with the three axial perineal evaluation (TAPE) score. Quality-of
      life was evaluated by the patient assessment of constipation quality-of-life (PAC
      Qol) questionnaire administered preoperatively and after 1 year of follow-up.
      RESULTS: The preoperative median ODS score and TAPE score were comparable in both
      groups. After a median follow-up of 12 months (range 12-18 months), the median
      ODS score was 12 (range 10-20) in the STARR group and 9 (range 3-15) in the VRP
      one (p = 0.02), while the median TAPE score was 70.5 (IQR 60.6-77.3) in the
      former and 76.8 (IQR 70.2-89.7) in the latter (p = 0.01). Postoperatively the
      physical domain of the PAC-QoL score had a median value of 2.74 (IQR 1.7-3.75) in
      the STARR group compared to 1.5 (IQR 1-2.5) in the VRP group (p = 0.03). No major
      complications were recorded in either group. CONCLUSIONS: VRP and STARR can
      improve defecation in patients with ODS with minimal complications, but the
      overall pelvic wellness evaluated by the TAPE score improves significantly only
      after VRP, suggesting a better performance of VRP than STARR when overall pelvic
      floor function is concerned.

PMID- 29594748
TI  - Ultrathin NiCo2O4 nanowalls supported on a 3D nanoporous gold coated needle for
      non-enzymatic amperometric sensing of glucose.
AB  - A disposable needle-type of hybrid electrode was prepared from a core of
      stainless steel needle whose surface was modified with a 3D nanoporous
      gold/NiCo2O4 nanowall hybrid structure for electrochemical non-enzymatic glucose
      detection. This hybrid electrode, best operated at 0.45 V (vs. SCE) in solutions
      of pH 13 has a linear response in the 0.01 to 21 mM glucose concentration range,
      a response time of <1 s, and a 1 MUM detection limit (at an S/N ratio of 3). The
      remarkable enhancement compared to the solid gold/NiCo2O4 and stainless
      steel/NiCo2O4 hybrid electrodes in electrochemical performance is assumed to
      originate from the good electrical conductivity and large surface area of the
      hybrid electrode, which enhance the transport of mass and charge during
      electrochemical reactions. This biosensor was also applied to real sample
      analysis with little interferences. The electrode is disposable and considered to
      be a promising tool for non-enzymatic sensing of glucose in a variety of
      practical situations. Graphical abstract Ultrathin NiCo2O4 nanowalls supported on
      nanoporous gold that is coated on a stainless steel needle was fabricated for
      sensitive non-enzymatic amperometric sensing of glucose.

PMID- 29594749
TI  - Signalling probe displacement electrochemical aptasensor for malignant cell
      surface nucleolin as a breast cancer biomarker based on gold nanoparticle
      decorated hydroxyapatite nanorods and silver nanoparticle labels.
AB  - Nucleolin is a multifunctional protein that is markedly overexpressed on the
      surface of most cancer cells. By taking advantage of the high affinity and
      specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement
      electrochemical aptasensor was developed. The thiolated AS1411 aptamer was
      conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles
      (AuNPs). To further increase the electrical conductivity of the interface, the
      ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity
      was placed on the electrode surface. Then, the aptamer was immobilized on the
      modified electrode and conjugated to signalling c-DNA tagged with AgNPs (c
      DNA@AgNPs). In the presence of the MCF7 target cells, the signalling probe is
      displaced and released from the electrode surface. This leads to a decrease in
      the current that is proportional to the concentration of cancer cells in the
      range from 10 to 106 cells mL-1, with a detection limit as low as 8 +/- 2 cells
      mL-1 (n = 3) (based as 3sigma/m, where sigma is the standard deviation of the
      blank and m is the slope of the calibration plot). This method presents a
      promising tool for highly sensitive and selective detection of surface nucleolin
      on MCF7 cancer cells. Graphical abstract HApNR-AuNP-AS1411 aptamer nanocomposite
      as an electrochemical sensing interface was immobilized on the gold electrode
      surface and conjugated to signaling c-DNA tagged with AgNPs for determination of
      surface nucleolin on MCF7 cancer cells.

PMID- 29594750
TI  - Visual detection of melamine by using a ratiometric fluorescent probe consisting
      of a red emitting CdTe core and a green emitting CdTe shell coated with a
      molecularly imprinted polymer.
AB  - A composite ratiometric fluorescent probe is described for visual detection of
      melamine (MEL) in milk samples. It is based on the use of red emitting and green
      emitting CdTe quantum dots, and a mesoporous molecularly imprinted polymer. The
      red emitting QDs are embedded in the silica microsphere to serve as a core, and
      the green emitting QDs are coated on the surface of the silica microsphere as a
      shell. A molecularly imprinted polymer (MIP) with specific recognition sites for
      MEL was placed on the shell. If MEL is bound by the MIP, the green fluorescence
      is quenched due to hydrogen bond interaction. The red emission, in contrast,
      remains unchanged. Quenching leads to a change in the color of fluorescence from
      red-green to purely red. This effect allows for visual and instrumental detection
      of MEL. The mesoporous structure of the MIP reduces the mass transfer resistance
      and enhances the accessibility of sites for MEL. Response is linear in the 50
      1000 ng mL-1 MEL concentration range, and the limit of detection is 13 ng mL-1.
      The fluorescent probe was successfully applied to the analysis of MEL-spiked milk
      samples and gave recoveries between 94.1 and 98.7%, with 3.6-5.1% relative
      standard deviations. Graphical abstract Schematic of the preparation and
      detection of the composite probe. The probe was applied for the selective
      recognition and visual detection of melamine (MEL).

PMID- 29594751
TI  - Determination of the activity of telomerase in cancer cells by using BSA
      protected gold nanoclusters as a fluorescent probe.
AB  - Gold nanoclusters (AuNCs) protected with a bovine serum albumin (BSA) coating are
      known to emit red fluorescence (peaking at 650 nm) on photoexcitation with
      ultraviolet light (365 nm). On addition of Cu(II) ions, fluorescence is quenched
      because Cu(II) complexes certain amino acid units in the BSA chain. Fluorescence
      is, however, restored if pyrophosphate (PPi) is added because it will chelate
      Cu(II) and remove it from the BSA coating on the AuNCs. Because PPi is involved
      in the function of telomerase, the BSA@AuNCs loaded with Cu(II) can act as a
      fluorescent probe for determination of the activity of telomerase. A fluorescent
      assay was worked out for telomerase that is highly sensitive and has a wide
      linear range (10 nU to 10 fM per mL). The fluorescent probe was applied to the
      determination of telomerase activity in cervix carcinoma cells via imaging. It is
      shown that tumor cells can be well distinguished from normal cells by monitoring
      the differences in intracellular telomerase activity. Graphical abstract Gold
      nanoclusters (AuNCs) protected by bovine serum albumin (BSA) and displaying red
      photoluminescence were prepared as fluorescent probe for the determination of
      telomerase activity and used for imaging of cervix carcinoma (HeLa) cells.

PMID- 29594753
TI  - Next-Generation Sequencing of Hepatitis C Virus (HCV) Mixed-Genotype Infections
      in Anti-HCV-Negative Blood Donors.
AB  - The infection with more than one hepatitis C virus (HCV) genotype especially in
      subjects with a high risk of multiple HCV exposures has been demonstrated. The
      role of HCV mixed-genotype infection in viral persistence and treatment effect is
      not fully understood. The prevalence of such infection varies greatly depending
      on the technique used for genotype determination and studied population. Next
      generation sequencing (NGS) which is suitable for extensive analysis of complex
      viral populations is a method of choice for studying mixed infections. The aim of
      the present study was to determine the prevalence of mixed-genotype HCV
      infections in the Polish seronegative, HCV-RNA-positive blood donors (n = 76).
      Two-step PCR was used for amplification of 5'-UTR of HCV. Using pyrosequencing
      altogether, 381,063 reads were obtained. The raw reads were trimmed and subjected
      to similarity analysis against the entire unfiltered NCBI nt database. Results
      obtained from NGS were compared with the standard genotyping. One (1.3%) mixed
      genotype [3a, 2989 reads (94.8%); 1b, 164 reads (5.2%)] infection was found in a
      sample diagnosed as genotype 3a only by routine testing. Two samples were
      identified with different genotypes, compared to routine testing. In conclusion,
      NGS is a sensitive method for HCV genotyping. The prevalence of mixed-genotype
      HCV infections in blood donors is low.

PMID- 29594752
TI  - Analysis on the influence of forest soil characteristics on radioactive Cs
      infiltration and evaluation of residual radioactive Cs on surfaces.
AB  - We investigated the depth profiles of radioactive Cs, ignition loss, and cation
      exchange capacity (CEC) in five types of forest soils sampled using scraper
      plates. We then simulated the monitored depth profiles in a compartment model,
      taking ignition loss as a parameter based on experimental results showing a
      positive correlation between ignition loss and the CEC. The calculated values
      were comparable with the monitored values, though some discrepancy was observed
      in the middle of the soil layer. Based on decontamination data on the surface
      dose rate and surface contamination concentration, we newly defined a surface
      residual index (SRI) to evaluate the residual radioactive Cs on surfaces. The SRI
      value tended to gradually decrease in forests and unpaved roads and was much
      smaller in forests and on unpaved roads than on paved roads. The radioactive Cs
      was assumed to have already infiltrated underground 18 months after the nuclear
      power plant accident, and the sinking was assumed to be ongoing. The SRI values
      measured on paved roads suggested that radioactive Cs remained on the surfaces,
      though a gradual infiltration was observed towards the end of the monitoring
      term. The SRI value is thought to be effective in grasping the rough condition of
      residual radioactive Cs quickly at sites of decontamination activity in the
      field. The SRI value may be serviceable for actual contamination works after
      further research is done to elucidate points such as the relation between the SRI
      and the infiltration of radioactive Cs in various types of objects.

PMID- 29594754
TI  - Improvement in Gait Pattern After Knee Arthroplasty Followed by Proprioceptive
      Neuromuscular Facilitation Physiotherapy.
AB  - The aim of the study was to assess the influence of a physiotherapy program based
      on proprioceptive neuromuscular facilitation (PNF) on kinematic gait pattern
      after total knee arthroplasty. This comparative study included two groups of
      patients qualified for total surgical knee joint replacement due to
      osteoarthritis: a study group and a control group, either consisting of 28
      patients of a matched age range of 55-90 years. Following surgery, 4 days after
      standard postoperative rehabilitation, the study patients were subjected to a 3
      week-long therapist-assisted rehabilitation based on PNF principles (10 sessions
      of 75 min each), whereas control patients were discharged with instructions on
      how to exercise in the home setting. The outcome consisted of spatial-temporal
      gait parameters that were assessed at three time points: a day before surgery and
      then 1 month and 6 months after. The findings were that PNF caused substantial,
      sustained improvements in gait kinematics, shortening the stance phases, gait
      cycle duration, and double support phase and prolonging swing phase velocity,
      gait velocity, cadence, step length, and gait cycle length. Also, postsurgical
      pain was evidently less. We conclude that the individually tailored PNF
      rehabilitation program is superior compared to a standard recommendation of home
      based physiotherapy in terms of improving gait kinematic pattern as well as
      psychological aspects related to pain perception in patients after knee
      arthroplasty.

PMID- 29594755
TI  - Dual approach for the colorimetric determination of unamplified microRNAs by
      using citrate capped gold nanoparticles.
AB  - The authors describe a method for the colorimetric determination of unamplified
      microRNA. It is based on the use of citrate-capped gold nanoparticles (AuNPs)
      and, alternatively, a microRNA-probe hybrid or a magnetically extracted microRNA
      that serve as stabilizers against the salt-induced aggregation of AuNPs. The
      absorbance ratios A525/A625 of the reacted AuNP solutions were used to quantify
      the amount of microRNA. The assay works in the range of 5-25 pmol microRNA. The
      lower limit of detection (LOD) is 10 pmol. The performance of the method was
      tested by detection of microRNA-210-3p in totally extracted urinary microRNA from
      normal, benign, and bladder cancer subjects. The sensitivity and specificity for
      qualitative detection of urinary microRNA-210-3p using the assay are 74% and 88%
      respectively, which is consistent with real time PCR based assays. The assay was
      applied to the determination of specific microRNA by using its specific oligo
      targeter or following magnetic isolation of the desired microRNA. The method is
      simple, cost-efficient, has a short turn-around time and requires minimal
      equipment and personnel. Graphical abstract Schematic of the two detection
      schemes: In the first approach, matched microRNA hybridizes with its specific
      probe to stabilize gold nanoparticles (AuNPs) against salt induced aggregation
      and to leave the red color of the AuNPs unchanged. In the second one, microRNA
      extracted via magnetic nanoparticles (MNP) stabilizes AuNPs against aggregation.

PMID- 29594757
TI  - Operative time and length of stay is similar between robotic assisted and
      laparoscopic colon and rectal resections.
AB  - Robotic-assisted surgery is increasingly being utilized for colorectal surgery.
      Data are scarce and contradictory when outcomes are compared between robotic and
      laparoscopic surgery. All patients undergoing minimally invasive colorectal
      surgery were compared from 2011 to 2016. Outcomes between the two groups were
      statistically analyzed. p < 0.05 was considered statistically significant. 185
      patients underwent laparoscopic resection and 70 underwent robotic resection.
      Demographics, ASA score, and BMI were similar between the two groups (p > 0.05).
      There was no statistical difference in median length of stay between laparoscopic
      and robotic colon (both 4 days; p = 0.5) and rectal (6 vs 4.5 days; p = 0.2)
      resections. Median operative times were also similar between the two approaches
      for colon (150.5 vs 169.5 min, p = 0.2) and rectal (197.0 vs 231.5 min, p = 0.9)
      resections. There was also no difference in operative time between the two
      approaches for right (median = 137 vs 130.5 min; p = 0.9) and left (median =
      162.0 vs 170.5 min; p = 0.6) colectomies. Robotic surgery results in similar
      operative times and length of stay as laparoscopic surgery for patients
      undergoing colon and rectal resections.

PMID- 29594756
TI  - The Molecular Differentiation of Anatomically Paired Left and Right Mantles of
      the Pacific Oyster Crassostrea gigas.
AB  - Left-right (L-R) asymmetry is controlled by gene regulation pathways for the L-R
      axis, and in vertebrates, the gene Pitx2 in TGF-beta signaling pathway plays
      important roles in the asymmetrical formation of organs. However, less is known
      about the asymmetries of anatomically identical paired organs, as well as the
      transcriptional regulation mechanism of the gene Pitx in invertebrates. Here, we
      report the molecular biological differences between the left and right mantles of
      an invertebrate, the Pacific oyster Crassostrea gigas, and propose one possible
      mechanism underlying those differences. RNA sequencing (RNA-seq) analysis
      indicated that the paired organs showed different gene expression patterns,
      suggesting possible functional differences in shell formation, pheromone
      signaling, nerve conduction, the stress response, and other physiological
      processes. RNA-seq and real-time qPCR analysis indicated high right-side
      expression of the Pitx homolog (cgPitx) in oyster mantle, supporting a conserved
      role for Pitx in controlling asymmetry. Methylation-dependent restriction-site
      associated DNA sequencing (MethylRAD) identified a methylation site in the
      promoter region of cgPitx and showed significantly different methylation levels
      between the left and right mantles. This is the first report, to our knowledge,
      of such a difference in methylation in spiralians, and it was further confirmed
      in 18 other individuals by using a pyrosequencing assay. The miRNome analysis and
      the TGF-beta receptor/Smad inhibition experiment further supported that several
      genes in TGF-beta signaling pathway may be related with the L/R asymmetry of
      oyster mantles. These results suggested that the molecular differentiation of the
      oyster's paired left and right mantles is significant, TGF-beta signaling pathway
      could be involved in establishing or maintaining the asymmetry, and the cgPitx
      gene as one of genes in this pathway; the different methylation levels in its
      promoter regions between L/R mantles was the one of possible mechanisms
      regulating the left-right functional differentiation.

PMID- 29594758
TI  - Voltammetric chiral discrimination of tryptophan using a multilayer nanocomposite
      with implemented amino-modified beta-cyclodextrin as recognition element.
AB  - An electrochemical chiral multilayer nanocomposite was prepared by modifying a
      glassy carbon electrode (GCE) via opposite-charge adsorption of amino-modified
      beta-cyclodextrin (NH2-beta-CD), gold-platinum core-shell microspheres (Au@Pts),
      polyethyleneimine (PEI), and multi-walled carbon nanotubes (MWCNTs). The modified
      GCE was applied to the enantioselective voltammetric determination of tryprophan
      (Trp). The Au@Pts enable an effective immobilization of the chiral selector (NH2
      beta-CD) and enhance the electrochemical performance. Scanning electron
      microscopy, transmission electron microscopy, UV-vis spectroscopy, FTIR and
      electrochemical methods were used to characterize the nanocomposite. Trp
      enantiomers were then determined by differential pulse voltammetry (DPV) (with a
      peak potential of +0.7 V vs. Ag/AgCl). The recognition efficiency was expressed
      by an increase in peak height by about 32% for DPV determinations of L-Trp
      compared to D-Trp in case of a 5 mM Trp solution of pH 7.0. Response was linear
      in the 10 MUM to 5.0 mM concentration range, and the limits of detection were 4.3
      MUM and 5.6 MUM with electrochemical sensitivity of 43.5 MUA.MUM-1.cm-2 and 34.6
      MUA.MUM-1.cm-2 for L-Trp and D-Trp, respectively (at S/N = 3). Graphical Abstract
      Schematic of an electrochemical chiral multilayer nanocomposite composed of multi
      walled carbon nanotubes (MWCNTs), polyethyleneimine (PEI), gold-platinum core
      shell microspheres (Au@Pt) and amino-modified beta-cyclodextrin (NH2-beta-CD). It
      was prepared by modifying a glassy carbon electrode (GCE) for enantioselective
      voltammetric determination of tryptophan (Trp) enantiomers.

PMID- 29594759
TI  - MCP-1 is overexpressed in triple-negative breast cancers and drives cancer
      invasiveness and metastasis.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive type of
      breast cancer that lacks ER/PR and HER2 receptors. Hence, there is urgency in
      developing new or novel therapeutic strategies for treatment of TNBC. Our study
      shows that the Monocyte Chemoattractant Protein-1 (MCP-1) is a marker associated
      with TNBC and may play a key role in TNBC disease progression. EXPERIMENTAL
      DESIGN: ELISA method was used to measure secreted MCP-1, and mRNA levels were
      determined by Real-time PCR in numerous cancer cell lines, representing various
      breast cancer subtypes. Cellular invasiveness was determined by Boyden chamber
      assay. RESULTS: Our data show that MCP-1 is upregulated in TNBC cell lines both
      transcriptionally as well as in secreted protein levels compared to ER-positive
      luminal cell line, MCF-7. Breast cancer patients, with Basal or Claudin-low
      subtypes, also showed high expression of MCP-1. MCP-1 treatment induced cell
      invasion in various breast cancer cell types, without affecting cell
      proliferation. Small molecule antagonists against Chemokine Receptor 2 (CCR2),
      cognate receptor for MCP-1 as well as the MAP kinase pathway inhibitor U0126
      negatively affected MCP-1 induced MCF-7 cell invasion. This suggests that MCP-1
      CCR2 axis may regulate invasiveness via the MAP Kinase pathway. Knocking down MCP
      1 decreased cell invasion in TNBC cell line BT-549, along with downregulation of
      key epithelial to mesenchymal transition markers, N-cadherin and Vimentin.
      CONCLUSION: Our study suggests that MCP-1 mediated pathways could be potential
      therapeutic targets for the treatment of TNBC, and could reduce cancer health
      disparities.

PMID- 29594761
TI  - Amperometric nonenzymatic sensing of glucose at very low working potential by
      using a nanoporous PdAuNi ternary alloy.
AB  - The authors present a nonenzymatic sensor for glucose that has an exceedingly low
      working potential which makes the sensor highly selective over other
      electroactive species. The sensor is based on the use of a glassy carbon
      electrode (GCE) that was modified with a nanoporous PdAuNi alloy (np-PdAuNi). The
      PdAuNi alloy nanostructure displays enhanced electrocatalytic activity for
      glucose oxidation (compared to PdNi alloys). The modified GCE enables
      amperometric sensing of glucose at a typical working electrode potential of 0.0 V
      vs. SCE in solutions of pH 13 containing 0.1 M NaCl. Response is linear in the 5
      to 100 MUM concentration range, with a 1.7 MUM detection limit (at an S/N ratio
      of 3). For higher concentrations deviations from linearity were found. The method
      is selective and reproducible. The modified electrode was applied to the
      determination of glucose in human serum. Graphical Abstract Nanoporous PdAuNi
      alloy with three-dimensional bicontinuous nanosponge architecture was
      successfully prepared via chemical dealloying. The electrochemical nonenzymatic
      glucose sensor shows a low working potential, wide linear range, good
      sensitivity, low detection limit and excellent selectivity.

PMID- 29594760
TI  - CMV Infection in Pediatric IBD.
AB  - PURPOSE OF REVIEW: Patients with inflammatory bowel disease (IBD) are predisposed
      to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly
      ulcerative colitis (UC), is related to severe or steroid-refractory disease. The
      aim of this review is to summarize the data on the prevalence and role of CMV
      colitis in children with IBD. RECENT FINDINGS: Data on CMV colitis in children
      continue to be very limited due to its rarity. As in adults, children with
      coexisting UC and CMV tend to have more severe colitis, are resistant to
      corticosteroids, and are at high risk for colectomies on short- and long-term
      follow-up. In children, as in adults, the significance of CMV colitis, in terms
      of whether CMV is a pathogen that aggravates acute severe colitis or simply
      reflects disease severity, is still unknown.

PMID- 29594763
TI  - Erratum to: Sexual Dimorphism and Estrogen Action in Mouse Liver.

PMID- 29594762
TI  - Folic acid modified copper nanoclusters for fluorescent imaging of cancer cells
      with over-expressed folate receptor.
AB  - Water-soluble and functional copper nanoclusters (CuNCs) were prepared by using
      folic acid (FA) that serves both as a reducing reagent and a stabilizer. FA also
      acts as a functional ligand on the surface of the CuNCs, and this can be
      exploited to target the folate receptor which is over-expressed on the surface of
      HeLa cells. The FA-modified CuNCs nanoclusters have an average size of ca. 0.9 nm
      and are stable in aqueous medium for 30 days. Under photoexcitation at lambdaex
      270 and 350 nm, the FA-CuNCs display strong blue fluorescence with an emission
      peak at 440 nm. The FA-CuNCs exhibit low cytotoxicity and favorable
      biocompatibility as demonstrated by an MTT assay. A cell viability of >80% is
      found when incubating HeLa cells for 20 h with FA-CuNCs at levels of up to 200
      MUg mL-1. The targeting capability of the FA-CuNCs is demonstrated by live cell
      imaging. It is shown that HeLa cells with over-expressed folate receptor are much
      brighter than A549 cells where the receptor is not over-expressed. This is
      further corroborated by the fact that the copper content in HeLa cells (1.5
      pg/cell) is 6.5-fold higher than that of A549 cells (0.23 pg/cell), both measured
      after the same incubation time of 3 h. If free FA is introduced into the cell
      culture medium, the folate receptors will be preoccupied with FA, and this
      results in a significant decrease in the cellular uptake of the FA-CuNCs by HeLa
      cells. Graphical Abstract Biocompatible copper nanoclusters (CuNCs) coated with
      folic acid (FA) were prepared and are shown to be viable probes for the
      differentiation between FR-positive HeLa cells and FR-negative A549 cells.

PMID- 29594764
TI  - Computer-Aided Drug Design: An Overview.
AB  - The term drug design describes the search of novel compounds with biological
      activity, on a systematic basis. In its most common form, it involves
      modification of a known active scaffold or linking known active scaffolds,
      although de novo drug design (i.e., from scratch) is also possible. Though highly
      interrelated, identification of active scaffolds should be conceptually separated
      from drug design. Traditionally, the drug design process has focused on the
      molecular determinants of the interactions between the drug and its known or
      intended molecular target. Nevertheless, current drug design also takes into
      consideration other relevant processes than influence drug efficacy and safety
      (e.g., bioavailability, metabolic stability, interaction with antitargets).This
      chapter provides an overview on possible approaches to identify active scaffolds
      (including in silico approximations to approach that task) and computational
      methods to guide the subsequent optimization process. It also discusses in which
      situations each of the overviewed techniques is more appropriate.

PMID- 29594765
TI  - Prediction of Human Drug Targets and Their Interactions Using Machine Learning
      Methods: Current and Future Perspectives.
AB  - Identification of drug targets and drug target interactions are important steps
      in the drug-discovery pipeline. Successful computational prediction methods can
      reduce the cost and time demanded by the experimental methods. Knowledge of
      putative drug targets and their interactions can be very useful for drug
      repurposing. Supervised machine learning methods have been very useful in drug
      target prediction and in prediction of drug target interactions. Here, we
      describe the details for developing prediction models using supervised learning
      techniques for human drug target prediction and their interactions.

PMID- 29594766
TI  - Practices in Molecular Docking and Structure-Based Virtual Screening.
AB  - Drug discovery has evolved significantly over the past two decades. Progress in
      key areas such as molecular and structural biology has contributed to the
      elucidation of the three-dimensional structure and function of a wide range of
      biological molecules of therapeutic interest. In this context, the integration of
      experimental techniques, such as X-ray crystallography, and computational
      methods, such as molecular docking, has promoted the emergence of several areas
      in drug discovery, such as structure-based drug design (SBDD). SBDD strategies
      have been broadly used to identify, predict and optimize the activity of small
      molecules toward a molecular target and have contributed to major scientific
      breakthroughs in pharmaceutical R&D. This chapter outlines molecular docking and
      structure-based virtual screening (SBVS) protocols used to predict the
      interaction of small molecules with the phosphatidylinositol-bisphosphate-kinase
      PI3Kdelta, which is a molecular target for hematological diseases. A detailed
      description of the molecular docking and SBVS procedures and an evaluation of the
      results are provided.

PMID- 29594767
TI  - Phylogenetic and Other Conservation-Based Approaches to Predict Protein
      Functional Sites.
AB  - Proteins use their functional regions to exploit various activities, including
      binding to other proteins, nucleic acids, or drugs. Functional sites of the
      proteins have a tendency to be more conserved than the rest of the protein
      surface. Therefore, detection of the conserved residues using phylogenetic
      analysis is a general approach to predict functionally critical residues. In this
      chapter, we describe some of the available methods to predict functional sites
      and demonstrate a complete pipeline with tool alternatives at several steps. We
      explain the standard procedure and all intermediate stages including homology
      detection with BLAST search, multiple sequence alignment (MSA) and the
      construction of a phylogenetic tree for a given query sequence. Additionally, we
      demonstrate the prediction results of these methods on a case study. Finally, we
      discuss the possible challenges and bottlenecks throughout the pipeline. Our step
      by-step description about the functional site prediction could be a helpful
      resource for the researchers interested in finding protein functional sites, to
      be used in drug discovery research.

PMID- 29594768
TI  - De Novo Design of Ligands Using Computational Methods.
AB  - De novo design technique is complementary to high-throughput virtual screening
      and is believed to contribute in pharmaceutical development of novel drugs with
      desired properties at a very low cost and time-efficient manner. In this chapter,
      we outline the basic de novo design concepts based on computational methods with
      an example.

PMID- 29594769
TI  - Molecular Dynamics Simulation and Prediction of Druggable Binding Sites.
AB  - Binding site identification and druggability evaluation are two essential steps
      in structure-based drug design. A druggable binding site tends to have high
      binding affinity to drug-like molecules. Predicting such sites can have a
      significant impact on a drug design campaign. This chapter focuses on summarizing
      the different methods that are used to predict druggable binding sites. The
      chapter also discusses the importance of including protein flexibility in the
      search process and the use of molecular dynamics simulations to address this
      aspect. Case studies from the literature are also summarized and discussed. We
      hope that this chapter would provide an overview on the different methods
      employed in binding site identification evaluation.

PMID- 29594770
TI  - Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein
      Ligand Docking Method.
AB  - Virtual screening is a computational technique for predicting a potent binding
      compound for a receptor protein from a ligand library. It has been a widely used
      in the drug discovery field to reduce the efforts of medicinal chemists to find
      hit compounds by experiments.Here, we introduce our novel structure-based virtual
      screening program, PL-PatchSurfer, which uses molecular surface representation
      with the three-dimensional Zernike descriptors, which is an effective
      mathematical representation for identifying physicochemical complementarities
      between local surfaces of a target protein and a ligand. The advantage of the
      surface-patch description is its tolerance on a receptor and compound structure
      variation. PL-PatchSurfer2 achieves higher accuracy on apo form and
      computationally modeled receptor structures than conventional structure-based
      virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for
      targets that do not have their crystal structures. The program is provided as a
      stand-alone program at http://kiharalab.org/plps2 . We also provide files for two
      ligand libraries, ChEMBL and ZINC Drug-like.

PMID- 29594771
TI  - Fragment-Based Ligand Designing.
AB  - Fragment-based drug design strategies have been used in drug discovery since it
      was first demonstrated using experimental structural biology techniques such as
      nuclear magnetic resonance (NMR) and X-ray crystallography. The underlying idea
      is that existing or new chemical entities with known desirable properties may
      serve both as tool compounds and as starting points for hit-to-lead expansion.
      Despite the recent advancements, there remain challenges to overcome, such as
      assembly of the synthetically feasible structures, development of scoring
      functions to correlate structure and their activities, and fine tuning of the
      promising molecules. This chapter first covers the theoretical background needed
      to understand the concepts and the challenges related to the field of study,
      followed by the description of important protocols and related software. Case
      studies are presented to demonstrate practical applications.

PMID- 29594772
TI  - Molecular Dynamics as a Tool for Virtual Ligand Screening.
AB  - Rational drug design is essential for new drugs to emerge, especially when the
      structure of a target protein or catalytic enzyme is known experimentally. To
      that purpose, high-throughput virtual ligand screening campaigns aim at
      discovering computationally new binding molecules or fragments to inhibit a
      particular protein interaction or biological activity. The virtual ligand
      screening process often relies on docking methods which allow predicting the
      binding of a molecule into a biological target structure with a correct
      conformation and the best possible affinity. The docking method itself is not
      sufficient as it suffers from several and crucial limitations (lack of protein
      flexibility information, no solvation effects, poor scoring functions, and
      unreliable molecular affinity estimation).At the interface of computer techniques
      and drug discovery, molecular dynamics (MD) allows introducing protein
      flexibility before or after a docking protocol, refining the structure of protein
      drug complexes in the presence of water, ions and even in membrane-like
      environments, and ranking complexes with more accurate binding energy
      calculations. In this chapter we describe the up-to-date MD protocols that are
      mandatory supporting tools in the virtual ligand screening (VS) process. Using
      docking in combination with MD is one of the best computer-aided drug design
      protocols nowadays. It has proved its efficiency through many examples, described
      below.

PMID- 29594773
TI  - Building Molecular Interaction Networks from Microarray Data for Drug Target
      Screening.
AB  - Potential drug targets for the disease treatment can be identified from
      microarray studies on differential gene expression of patients and healthy
      participants. Here, we describe a method to use the information of differentially
      expressed (DE) genes obtained from microarray studies to build molecular
      interaction networks for identification of pivotal molecules as potential drug
      targets. The quality control and normalization of the microarray data are
      conducted with R packages simpleaffy and affy, respectively. The DE genes with
      adjusted P values less than 0.05 and log fold changes larger than 1 or less than 
      1 are identified by limma package to construct a molecular interaction network
      with InnateDB. The genes with significant connectivity are identified by the
      Cytoscape app jActiveModules. The interactions among the genes within a module
      are tested by psych package to determine their associations. The gene pairs with
      significant association and known protein structures according to the Protein
      Data Bank are selected as potential drug targets. As an example for drug target
      screening, we demonstrate how to identify potential drug targets from a molecular
      interaction network constructed with the DE genes of significant connectivity,
      using a microarray dataset of type 2 diabetes mellitus.

PMID- 29594774
TI  - Absolute Alchemical Free Energy Calculations for Ligand Binding: A Beginner's
      Guide.
AB  - Many thermodynamic quantities can be extracted from computer simulations that
      generate an ensemble of microstates according to the principles of statistical
      mechanics. Among these quantities is the free energy of binding of a small
      molecule to a macromolecule, such as a protein. Here, we present an introductory
      overview of a protocol that allows for the estimation of ligand binding free
      energies via molecular dynamics simulations. While we focus on the binding of
      organic molecules to proteins, the approach is in principle transferable to any
      pair of molecules.

PMID- 29594775
TI  - Evaluation of Protein-Ligand Docking by Cyscore.
AB  - Protein-ligand docking is a powerful method in drug discovery. The reliability of
      docking can be quantified by RMSD between a docking structure and an
      experimentally determined one. However, most experimentally determined structures
      are not available in practice. Evaluation by scoring functions is an alternative
      for assessing protein-ligand docking results. This chapter first provides a brief
      introduction to scoring methods used in docking. Then details are provided on how
      to use Cyscore programs. Finally it describes a case study for evaluation of
      protein-ligand docking.

PMID- 29594776
TI  - Molecular Dynamics Simulations of Protein-Drug Complexes: A Computational
      Protocol for Investigating the Interactions of Small-Molecule Therapeutics with
      Biological Targets and Biosensors.
AB  - MD simulations provide a powerful tool for the investigation of protein-drug
      complexes. The following chapter uses the aryl acylamidase-acetaminophen system
      as an example to describe a general protocol for preparing and running
      simulations of protein-drug complexes, complete with a step-by-step tutorial. The
      described approach is broadly applicable toward the study of drug interactions in
      the context of both biological targets and biosensing enzymes.

PMID- 29594777
TI  - Prediction and Optimization of Pharmacokinetic and Toxicity Properties of the
      Ligand.
AB  - A crucial factor for the approval and success of any drug is how it behaves in
      the body. Many drugs, however, do not reach the market due to poor efficacy or
      unacceptable side effects. It is therefore important to take these into
      consideration early in the drug development process, both in the prioritization
      of potential hits, and optimization of lead compounds. In silico approaches offer
      a cost and time-effective approach to rapidly screen and optimize pharmacokinetic
      and toxicity properties. Here we demonstrate the use of the comprehensive
      analysis system pkCSM, to allow early identification of potential problems,
      prioritization of hits, and optimization of leads.

PMID- 29594778
TI  - Protein-Protein Docking in Drug Design and Discovery.
AB  - Protein-protein interactions (PPIs) are responsible for a number of key
      physiological processes in the living cells and underlie the pathomechanism of
      many diseases. Nowadays, along with the concept of so-called "hot spots" in
      protein-protein interactions, which are well-defined interface regions
      responsible for most of the binding energy, these interfaces can be targeted with
      modulators. In order to apply structure-based design techniques to design PPIs
      modulators, a three-dimensional structure of protein complex has to be available.
      In this context in silico approaches, in particular protein-protein docking, are
      a valuable complement to experimental methods for elucidating 3D structure of
      protein complexes. Protein-protein docking is easy to use and does not require
      significant computer resources and time (in contrast to molecular dynamics) and
      it results in 3D structure of a protein complex (in contrast to sequence-based
      methods of predicting binding interfaces). However, protein-protein docking
      cannot address all the aspects of protein dynamics, in particular the global
      conformational changes during protein complex formation. In spite of this fact,
      protein-protein docking is widely used to model complexes of water-soluble
      proteins and less commonly to predict structures of transmembrane protein
      assemblies, including dimers and oligomers of G protein-coupled receptors
      (GPCRs). In this chapter we review the principles of protein-protein docking,
      available algorithms and software and discuss the recent examples, benefits, and
      drawbacks of protein-protein docking application to water-soluble proteins,
      membrane anchoring and transmembrane proteins, including GPCRs.

PMID- 29594779
TI  - Automated Inference of Chemical Discriminants of Biological Activity.
AB  - Ligand-based virtual screening has become a standard technique for the efficient
      discovery of bioactive small molecules. Following assays to determine the
      activity of compounds selected by virtual screening, or other approaches in which
      dozens to thousands of molecules have been tested, machine learning techniques
      make it straightforward to discover the patterns of chemical groups that
      correlate with the desired biological activity. Defining the chemical features
      that generate activity can be used to guide the selection of molecules for
      subsequent rounds of screening and assaying, as well as help design new, more
      active molecules for organic synthesis.The quantitative structure-activity
      relationship machine learning protocols we describe here, using decision trees,
      random forests, and sequential feature selection, take as input the chemical
      structure of a single, known active small molecule (e.g., an inhibitor, agonist,
      or substrate) for comparison with the structure of each tested molecule.
      Knowledge of the atomic structure of the protein target and its interactions with
      the active compound are not required. These protocols can be modified and applied
      to any data set that consists of a series of measured structural, chemical, or
      other features for each tested molecule, along with the experimentally measured
      value of the response variable you would like to predict or optimize for your
      project, for instance, inhibitory activity in a biological assay or
      DeltaGbinding. To illustrate the use of different machine learning algorithms, we
      step through the analysis of a dataset of inhibitor candidates from virtual
      screening that were tested recently for their ability to inhibit GPCR-mediated
      signaling in a vertebrate.

PMID- 29594780
TI  - Computational Exploration of Conformational Transitions in Protein Drug Targets.
AB  - Protein drug targets vary from highly structured to completely disordered; either
      way dynamics governs function. Hence, understanding the dynamical aspects of how
      protein targets function can enable improved interventions with drug molecules.
      Computational approaches offer highly detailed structural models of protein
      dynamics which are becoming more predictive as model quality and sampling power
      improve. However, the most advanced and popular models still have errors owing to
      imperfect parameter sets and often cannot access longer timescales of many
      crucial biological processes. Experimental approaches offer more certainty but
      can struggle to detect and measure lightly populated conformations of target
      proteins and subtle allostery. An emerging solution is to integrate available
      experimental data into advanced molecular simulations. In the future, molecular
      simulation in combination with experimental data may be able to offer detailed
      models of important drug targets such that improved functional mechanisms or
      selectivity can be accessed.

PMID- 29594781
TI  - Applications of the NRGsuite and the Molecular Docking Software FlexAID in
      Computational Drug Discovery and Design.
AB  - Docking simulations help us understand molecular interactions. Here we present a
      hands-on tutorial to utilize FlexAID (Flexible Artificial Intelligence Docking),
      an open source molecular docking software between ligands such as small molecules
      or peptides and macromolecules such as proteins and nucleic acids. The tutorial
      uses the NRGsuite PyMOL plugin graphical user interface to set up and visualize
      docking simulations in real time as well as detect and refine target cavities.
      The ease of use of FlexAID and the NRGsuite combined with its superior
      performance relative to widely used docking software provides nonexperts with an
      important tool to understand molecular interactions with direct applications in
      structure-based drug design and virtual high-throughput screening.

PMID- 29594782
TI  - Calculation of Thermodynamic Properties of Bound Water Molecules.
AB  - Water molecules in the binding site of a protein significantly influence protein
      structure and function, for example, by mediating protein-ligand interactions or
      in form of desolvation as driving force for ligand binding. The knowledge about
      location and thermodynamic properties of water molecules in the binding site is
      crucial to the understanding of protein function. This chapter describes the
      method of calculating the location and thermodynamic properties of bound water
      molecules from molecular dynamics (MD) simulation trajectories. Thermodynamic
      profiles of water molecules can be calculated either with or without the presence
      of a bound ligand based on the scientific problem. The location and thermodynamic
      profile of hydration sites mediating the protein-ligand interactions is important
      for understanding protein-ligand binding. The protein desolvation free energy can
      be estimated for any ligand by summation of the hydration site free energies of
      the displaced hydration sites. The WATsite program with an easy-to-use graphical
      user interface (GUI) based on PyMOL was developed for those calculations and is
      discussed in this chapter. The WATsite program and its PyMOL plugin are available
      free of charge from
      http://people.pharmacy.purdue.edu/~mlill/software/watsite/version3.shtml .

PMID- 29594783
TI  - Enhanced Molecular Dynamics Methods Applied to Drug Design Projects.
AB  - Nobel Laureate Richard P. Feynman stated: "[...] everything that living things do
      can be understood in terms of jiggling and wiggling of atoms [...]." The
      importance of computer simulations of macromolecules, which use classical
      mechanics principles to describe atom behavior, is widely acknowledged and
      nowadays, they are applied in many fields such as material sciences and drug
      discovery. With the increase of computing power, molecular dynamics simulations
      can be applied to understand biological mechanisms at realistic timescales. In
      this chapter, we share our computational experience providing a global view of
      two of the widely used enhanced molecular dynamics methods to study protein
      structure and dynamics through the description of their characteristics, limits
      and we provide some examples of their applications in drug design. We also
      discuss the appropriate choice of software and hardware. In a detailed practical
      procedure, we describe how to set up, run, and analyze two main molecular
      dynamics methods, the umbrella sampling (US) and the accelerated molecular
      dynamics (aMD) methods.

PMID- 29594784
TI  - AGGRESCAN3D: Toward the Prediction of the Aggregation Propensities of Protein
      Structures.
AB  - Protein aggregation is responsible for the onset and spread of many human
      diseases, ranging from neurodegenerative disorders to cancer and diabetes.
      Moreover, it is one of the major bottlenecks for the production of protein-based
      therapeutics such as antibodies or enzymes. AGGRESCAN3D (A3D) is a web server
      aimed to identify and evaluate structural aggregation prone regions, overcoming
      the limitations of sequence-based algorithms in the prediction of the aggregation
      propensity of globular proteins. A3D allows the redesign of protein solubility by
      predicting in silico the impact of mutations and protein conformational
      fluctuations on the aggregation of native polypeptides.

PMID- 29594785
TI  - Computational Analysis of Solvent Inclusion in Docking Studies of Protein
      Glycosaminoglycan Systems.
AB  - Glycosaminoglycans (GAGs) are a class of anionic linear periodic polysaccharides,
      which play a key role in many cell signaling related processes via interactions
      with their protein targets. In silico analysis and, in particular, application of
      molecular docking approaches to these systems still experience many challenges
      including the need of proper treatment of solvent, which is crucial for protein
      GAG interactions. Here, we describe two methods which we developed, to include
      solvent in the docking studies of protein-GAG systems: the first one allows to de
      novo predict favorable positions of water molecules as a part of a rigid receptor
      to be used for further molecular docking; the second one utilizes targeted
      molecular dynamics in explicit solvent for molecular docking.

PMID- 29594786
TI  - Understanding G Protein-Coupled Receptor Allostery via Molecular Dynamics
      Simulations: Implications for Drug Discovery.
AB  - Unraveling the mystery of protein allostery has been one of the greatest
      challenges in both structural and computational biology. However, recent advances
      in computational methods, particularly molecular dynamics (MD) simulations, have
      led to its utility as a powerful and popular tool for the study of protein
      allostery. By capturing the motions of a protein's constituent atoms, simulations
      can enable the discovery of allosteric hot spots and the determination of the
      mechanistic basis for allostery. These structural and dynamic studies can provide
      a foundation for a wide range of applications, including rational drug design and
      protein engineering. In our laboratory, the use of MD simulations and network
      analysis assisted in the elucidation of the allosteric hotspots and intracellular
      signal transduction of G protein-coupled receptors (GPCRs), primarily on one of
      the adenosine receptor subtypes, A2A adenosine receptor (A2AAR). In this chapter,
      we describe a method for calculating the map of allosteric signal flow in
      different GPCR conformational states and illustrate how these concepts have been
      utilized in understanding the mechanism of GPCR allostery. These structural
      studies will provide valuable insights into the allosteric and orthosteric
      modulations that would be of great help to design novel drugs targeting GPCRs in
      pathological states.

PMID- 29594787
TI  - Identification of Potential MicroRNA Biomarkers by Meta-analysis.
AB  - Meta-analysis statistically assesses the results (e.g., effect sizes) across
      independent studies that are conducted in accordance with similar protocols and
      objectives. Current genomic meta-analysis studies do not perform extensive re
      analysis on raw data because full data access would not be commonplace, although
      the best practice of open research for sharing well-formed data have been
      actively advocated. This chapter describes a simple and easy-to-follow method for
      conducting meta-analysis of multiple studies without using raw data. Examples for
      meta-analysis of microRNAs (miRNAs) are provided to illustrate the method. MiRNAs
      are potential biomarkers for early diagnosis and epigenetic monitoring of
      diseases. A number of miRNAs have been identified to be differentially expressed,
      i.e., overexpressed or underexpressed, under diseased states but only a small
      fraction would be highly effective biomarkers or therapeutic targets of diseases.
      The meta-analysis method as described in this chapter aims to identify the miRNAs
      that are consistently found dysregulated across independent studies as
      biomarkers.

PMID- 29594788
TI  - The effects of chalazion surgery on intraocular pressure and corneal topography.
AB  - PURPOSE: To evaluate the effects of chalazion surgery on intraocular pressure
      (IOP) and the biomechanical, topographic, and topometric properties of the
      cornea. METHODS: A total of 29 patients with upper eyelid chalazion were included
      in this study. All patients underwent preoperative and postoperative detailed
      ophthalmological examinations including scale of chalazion size; IOP (IOPcc and
      IOPg), corneal hysteresis, and corneal resistance factor measurements using
      ocular response analyser (ORA; Reichert Instruments, Depew, NY, USA); topographic
      and topometric properties of the cornea using Pentacam HR (Oculus GmbH, Wetzlar,
      HE, Germany). Preoperative and postoperative measurements were compared. RESULTS:
      The mean age of the patients was 29.07 +/- 13.74 years (18-54 years). The mean
      IOPcc was 15.82 +/- 4.20 mmHg preoperatively and 14.72 +/- 3.96 mmHg
      postoperatively, and the mean IOPg was 15.21 +/- 3.91 mmHg preoperatively and
      14.21 +/- 4.02 mmHg postoperatively (p = 0.020, p = 0.007, respectively). The
      mean central keratoconus index (CKI) was 1.006 +/- 0.01 preoperatively and 1.002
      +/- 0.01 postoperatively (p = 0.035). Other biomechanical, keratometric,
      topographic, and topometric parameters were similar before and after the surgery
      (all p > 0.05). CONCLUSION: To the best of our knowledge, this is the first
      report to suggest that IOP and CKI are decreased after the removal of upper
      eyelid chalazion.

PMID- 29594789
TI  - Outcomes of presbyopia-correcting intraocular lenses after laser in situ
      keratomileusis.
AB  - BACKGROUND: Laser in situ keratomileusis (LASIK) is the most common refractive
      surgery in young patients, which aims at providing a clear distance vision
      without the use of spectacles. With time, these patients develop symptomatic
      cataract, which affects activities of daily living, and to improve visual acuity,
      intraocular lens (IOL) implantation can be considered. In post-myopic LASIK
      patients, to allow continuation of spectacle independence, the implantation of
      presbyopia-correcting IOLs is a suitable option. The purpose of this
      retrospective case series is to report the visual outcome and quality in post
      myopic LASIK eyes after the implantation of AT LISA tri839MP IOL. METHOD: Twenty
      eyes of 13 patients with history of myopic LASIK within 20 years underwent
      phacoemulsification by one single surgeon. All eyes were implanted with AT LISA
      tri839PMP IOL, and their outcomes were evaluated at 6 months postoperation.
      RESULTS: The mean postoperative uncorrected distance visual acuity (VA) is 0.28
      +/- 0.29, while the corrected distance VA is 0.06 +/- 0.14. The mean
      postoperative uncorrected near VA is 0.02 +/- 0.05, while the corrected near VA
      is 0.01 +/- 0.02. The mean postoperative manifest refraction spherical equivalent
      (SE) is - 0.92 +/- 0.76D. There is a statistically significant difference between
      the preoperative and postoperative refraction (p = 0.02), which shows a
      postoperative myopic shift. There is also a statistically significant difference
      between the mean targeted SE and postoperative manifest refraction SE (p = 0.00).
      Only one out of 20 eyes (5%) reported halo and glare symptoms. Ten out of 20 eyes
      (50%) are able to achieve spectacles independence. CONCLUSION: In conclusion, in
      post-myopic LASIK eyes, AT LISA tri839MP provides a good visual outcome at both
      near and distance, but is more predictable at near than at distance. There is a
      myopic shift in the postoperative SE. Visual quality is satisfactory and has not
      been exacerbated. Most patients can remain to be spectacles free at all
      distances.

PMID- 29594790
TI  - Resolution of arterial aneurysms in idiopathic retinal vasculitis, aneurysms and
      neuroretinitis: a case report and review of literature.
AB  - PURPOSE: To report a case of resolution of retinal arterial aneurysms in a
      patient of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN)
      treated with oral steroids. METHODS: This study contains case report and review
      of literature. RESULTS: A 16-year-old girl with stage 2 IRVAN was treated with
      oral steroids alone. Fluorescein angiography confirmed the presence of aneurysms
      and absence of neovascularization in both eyes. The aneurysms resolved gradually
      over 4-month follow-up. CONCLUSIONS: This case demonstrates previously unreported
      reversibility of arterial aneurysms with steroid therapy alone in early stages of
      IRVAN.

PMID- 29594791
TI  - Repair of angle recession prevents pupillary capture of intrasclerally fixed
      intraocular lenses.
AB  - PURPOSE: We evaluated a new concept for treating pupillary capture of the
      intraocular lens (IOL) following intrascleral fixation of the IOL. Pupillary
      capture of the IOL is a common postoperative complication that occurs after
      suturing and intrascleral fixation of the IOL. In such cases, blunt trauma is
      often related to zonular dialysis, iris retraction, iridodonesis, and angle
      recession. Several methods such as barricading by suturing, pupilloplasty, and
      pars plana fixation are reported to prevent pupillary capture. Although
      effective, none of these techniques fix iris-malposition and angle recession. We
      considered that repairing angle recession could correct the iris position and
      prevent pupillary capture recurrence. METHODS: We repaired angle recession in
      four cases and have followed up. RESULTS: Pupillary capture was not observed in
      all three cases of larger IOLs for more than 9 months, but observed after 1 month
      in an IOL with normal 6 mm diameter, in which the angle was not properly lifted.
      CONCLUSION: In select cases, repairing angle recession may be useful for
      preventing pupillary capture after IOL suturing and intrascleral fixation.

PMID- 29594792
TI  - Ocular surface and respiratory tract damages from occupational, sub-chronic
      exposure to fluorspar: case report and other considerations.
AB  - OBJECTIVES: To report the ocular surface and respiratory tract damages due to a
      sub-chronic (3 months), occupational exposure to fluorspar dust in case of
      inconsistent use of personal protective equipment. METHODS: A 50-year-old man was
      referred to our clinic with bilateral conjunctival injection, ocular foreign body
      sensation and symptoms of ocular discomfort. He reported having 3 days before an
      urgent hospital admission for dyspnoea with odynophagia, hyposmia, nausea,
      vomiting, headache and asthenia. Otorhinolaryngological examination revealed a
      severe hypertrophic rhinopharyngitis and a significant decrease in overall
      sensitivity to olfactory stimuli. General anamnesis was negative for previous
      diseases or medication use. RESULTS: Ocular examination revealed a diffuse
      injection of the ocular surface with some areas of conjunctival and limbal
      ischaemia, a best-corrected visual acuity of 20/25 in both eyes, an intraocular
      pressure of 23 and 21 mmHg, respectively, in the right and in the left eyes, and
      a normal fundus oculi. Assessment of the tear film and ocular surface showed the
      presence of dry eye disease. Based on medical history and clinical tests, initial
      diagnostic hypothesis was ocular surface burn due to chemical exposure, i.e. to
      fluorspar. Therefore, anterior segment fluorescein angiography was performed to
      confirm the extension of conjunctival and limbal ischaemia. Thus, ocular
      ischaemia was detected in approximately 10 clock hours of limbus and in 50% of
      conjunctiva. CONCLUSIONS: The present work remarks the importance of using
      protective equipment for preventing ocular and respiratory tract damages in
      workers occupationally exposed to the 'acid-grade fluorite'.

PMID- 29594793
TI  - Sterile keratitis after uneventful corneal collagen cross-linking in a patient
      with Axenfeld-Rieger syndrome.
AB  - PURPOSE: To report on a keratoconus (KC) patient with Axenfeld-Rieger syndrome
      (ARS) who developed sterile keratitis after accelerated corneal collagen cross
      linking (CXL). METHODS: An 18-year-old patient with ARS and KC who had previously
      undergone intrastromal ring segment implantation underwent accelerated CXL (9
      mW/cm2 UVA intensity for 10 min). RESULTS: After uneventful surgery, the patient
      presented with severe photophobia, redness of the eye, and decreased vision 72 h
      following the procedure. Slit-lamp examination showed anterior multiple
      superficial stromal infiltrates in the central cornea with an overlying
      epithelium defect. Due to the lack of pain and absence of any pathogen from
      corneal samples, a diagnosis of sterile keratitis was considered. A combination
      of topical antibiotic and corticosteroid regimen was administered. Three months
      after CXL slit-lamp examination showed a mild stromal scar overlying the central
      cornea, which did not decrease visual acuity. CONCLUSIONS: The mechanism by which
      the sterile keratitis occurs following CXL remains unclear. For our case, the
      reason of post-CXL sterile keratitis could be considered as an immune response
      due to the staphylococcal antigens. Furthermore, the possible developmental
      disturbance of corneal stroma in ARS might have contributed to the development of
      post-CXL sterile keratitis.

PMID- 29594794
TI  - Case series of coexistence of polypoidal choroidal vasculopathy with other rare
      fundus diseases.
AB  - PURPOSE: To record the coexistence of polypoidal choroidal vasculopathy (PCV)
      with other rare fundus diseases in a Chinese population. METHOD: In this
      retrospective hospital-based study, a chart review of 861 patients with newly
      diagnosed PCV was performed. The clinical features of rare fundus comorbidities
      of PCV were recorded. RESULTS: Five eyes of 5 patients aged 63.4 +/- 11.22 years
      (0.58%) had PCV coexisting with other fundus diseases in the same eye. Of the 5
      PCV patients, 2 (0.23%) had myelinated nerve fiber, 2 (0.23%) had branch retinal
      vein occlusion, and 1 (0.12%) had retinal angiomatous proliferation. CONCLUSION:
      We reported rare fundus comorbidities of PCV in a large Chinese cohort. These
      comorbidities included myelinated nerve fiber, branch retinal vein occlusion and
      retinal angiomatous proliferation. The combination might constitute an accidental
      occurrence.

PMID- 29594795
TI  - Aptamer based fluorometric sulfamethazine assay based on the use of graphene
      oxide quantum dots.
AB  - The authors have developed a homogeneous "off-on" fluorometric method for the
      determination of the antibiotic sulfamethazine (SMZ). Aptamer against SMZ was
      labeled with graphene oxide quantum dots upon which the Graphene oxide quenched
      the blue fluorescence of the GOQDs. On addition of SMZ, the aptamers will bind
      SMZ and this will cause the release of GOQDs. As a result, fluorescence will be
      regenerated. Fluorescence, best measured at excitation/emission wavelengths of
      365/455 nm, increases linearly in the 8 pg.mL-1 to 60 ng.mL-1 SMZ concentration
      range, with a 5 pg.mL-1 detection limit. The method is reliable and was
      successfully applied to the determination of SMZ in spiked milk samples, with
      recoveries ranging from 89 to 96% depending on analyte concentration. Graphical
      abstract Graphene oxide quantum dots (GOQDs) were covalently bound to the aptamer
      (apt) against sulfamethazine (SMZ) and adsorbed on the surface of graphene oxide
      (GO). This results in quenching of the fluorescence of GOQDs. On addition of SMZ,
      fluorescence is restored due to the release of GOQD@apt from GO.

PMID- 29594796
TI  - Alternative mitochondrial respiratory chains from two crustaceans: Artemia
      franciscana nauplii and the white shrimp, Litopenaeus vannamei.
AB  - Mitochondrial ATP is synthesized by coupling between the electron transport chain
      and complex V. In contrast, physiological uncoupling of these processes allows
      mitochondria to consume oxygen at high rates without ATP synthesis. Such
      uncoupling mechanisms prevent reactive oxygen species overproduction. One of
      these mechanisms are the alternative redox enzymes from the mitochondrial
      respiratory chain, which may help cells to maintain homeostasis under stress
      independently of ATP synthesis. To date, no reports have been published on
      alternative redox enzymes in crustaceans mitochondria. Specific inhibitors were
      used to identify alternative redox enzymes in mitochondria isolated from Artemia
      franciscana nauplii, and the white shrimp, Litopenaeus vannamei. We report the
      presence of two alternative redox enzymes in the respiratory chain of A.
      franciscana nauplii, whose isolated mitochondria used glycerol-3-phosphate as a
      substrate, suggesting the existence of a glycerol-3-phosphate dehydrogenase. In
      addition, cyanide and octyl-gallate were necessary to fully inhibit this species'
      mitochondrial oxygen consumption, suggesting an alternative oxidase is present.
      The in-gel activity analysis confirmed that additional mitochondrial redox
      proteins exist in A. franciscana. A mitochondrial glycerol-3-phosphate
      dehydrogenase oxidase was identified by protein sequencing as part of a branched
      respiratory chain, and an alternative oxidase was also identified in this species
      by western blot. These results indicate different adaptive mechanisms from
      artemia to face environmental challenges related to the changing levels of oxygen
      concentration in seawater through their life cycles. No alternative redox enzymes
      were found in shrimp mitochondria, further efforts will determine the existence
      of an uncoupling mechanism such as uncoupling proteins.

PMID- 29594797
TI  - Preparation of a boronate affinity material with ultrahigh binding capacity for
      cis-diols by grafting polymer brush from polydopamine-coated magnetized graphene
      oxide.
AB  - Poly(3-acrylamidophenylboronic acid) (PAAPBA) was grafted onto polydopamine
      coated magnetic graphene oxide via surface-initiated atom transfer radical
      polymerization to obtain a new kind of boronate affinity material (BAM). The BAM
      possesses good water dispersity and adsorption capacities as high as 154, 357,
      588 and 1111 MUmol.g-1 for adenosine, salbutamol, dopamine and catechol,
      respectively. For the molecules without nitrogen atoms, the BAM can selectively
      capture the cis-diols under the interference of non-cis-diols. For molecules
      containing nitrogen, the non-cis-diols are also retained, but much less than the
      cis-diols. The selectivity can be improved by adding salts to facilitate
      complexation and to suppress the electrostatic interaction between cis-diols and
      the boronic acid ligand. The BAM was successfully employed to the enrichment of
      catecholamines from real urine samples. Results indicate that it is a promising
      material for the pretreatment of real samples. Graphical abstract Schematic of
      the preparation of an ultrahigh capacity boronate affinity material by grafting
      polymer brush from polydopamine coated magnetic graphene oxide. The material has
      good selectivity to cis-diol-containing molecules and can be applied to enrich
      catecholamines in urine samples.

PMID- 29594798
TI  - Improved quality of care for patients infected or colonised with ESBL-producing
      Enterobacteriaceae in a French teaching hospital: impact of an interventional
      prospective study and development of specific tools.
AB  - The increasing incidence of ESBL-producing Enterobacteriaceae (ESBL-E) in France
      prompted the publication of national recommendations in 2010. Based on these, we
      developed a toolkit and a warning system to optimise management of ESBL-E
      infected or colonised patients in both community and hospital settings. The
      impact of this initiative on quality of care was assessed in a teaching hospital.
      The ESBL toolkit was developed in 2011 during multidisciplinary meetings
      involving a regional network of hospital, private clinic and laboratory staff in
      Southeastern France. It includes antibiotic treatment protocols, a check list,
      mail templates and a patient information sheet focusing on infection control.
      Upon identification of ESBL-E, the warning system involves alerting the attending
      physician and the infectious disease (ID) advisor, with immediate, advice-based
      implementation of the toolkit. The procedure and toolkit were tested in our
      teaching hospital. Patient management was compared before and after
      implementation of the toolkit over two 3-month periods (July-October 2010 and
      2012). Implementation of the ESBL-E warning system and ESBL-E toolkit was tested
      for 87 patients in 2010 and 92 patients in 2012, resulting in improved patient
      management: expert advice sought and followed (16 vs 97%), information provided
      to the patient's general practitioner (18 vs 63%) and coding of the condition in
      the patient's medical file (17 vs 59%), respectively. Our multidisciplinary
      strategy improved quality of care for in-patients infected or colonised with ESBL
      E, increasing compliance with national recommendations.

PMID- 29594799
TI  - Managing ESBL-producing Enterobacteriaceae-related urinary tract infection in
      primary care: a tool kit for general practitioners.
AB  - In Southern France, approximately 4% of E. coli isolates from community-acquired
      urinary tract infections are extended spectrum beta-lactamase producers, while
      carriage rates for enterobacteriaceae (ESBL-E) range from 3 to 6%. General
      practitioners (GP) are unfamiliar with the management of patients harboring ESBL
      E. Providing them with a specific tool kit should assist in their therapeutic
      approach and optimize antimicrobial prescription an ESBL-E tool kit was developed
      by a multidisciplinary team: infectious diseases (ID) specialists,
      microbiologists, pharmacologists, and nursing home staff. This tool kit includes
      treatment protocols, GP and patient information leaflets, a list of infection
      control measures, and contact details of ID physicians for specialized advice. A
      community-based (including nursing homes) prospective study was conducted in 2012
      in Southeastern France to test the tool kit in the context of ESBL-E-related
      urinary tract infections (UTI). ESBL-E-related UTI were identified in 88
      patients, 66 GPs were contacted by the microbiology laboratory, 56 stated they
      were offered the tool kit, 48 said they had received it, and 41 stated they had
      read its contents. Use of the tool kit was significantly correlated with
      appropriate antibiotic prescription, which concerned 36/39 tool kit users versus
      13/20 non-users (p = 0.0125) and 40 GPs expressed an average satisfaction rate of
      4.2 on a scale of 0 to 5. Availability of a specific tool for managing patients
      harboring ESBL-E, now completed with a website, can assist community-based GPs
      and improve antimicrobial prescription.

PMID- 29594800
TI  - Diagnostic accuracy of the InBiOS AMD rapid diagnostic test for the detection of
      Burkholderia pseudomallei antigen in grown blood culture broth.
AB  - To assess the diagnostic and operational performance of the InBiOS AMD rapid
      diagnostic test (RDT) (Seattle, USA) for the detection of B. pseudomallei in
      grown blood culture broth. The InBiOS RDT is a lateral flow immunoassay in a
      strip format detecting B. pseudomallei capsular polysaccharide in culture fluids,
      marketed for research only. Broth of blood culture bottles (BacT/Alert,
      bioMerieux, Marcy L'Etoile, France) sampled in adult patients at the Sihanouk
      Hospital Center of HOPE, Phnom Penh, Cambodia, during 2010-2017 and stored at -
      80  degrees C was tested. They included samples grown with B. pseudomallei (n =
      114), samples with no growth (n = 12), and samples with growth of other pathogens
      (n = 139, among which Burkholderia cepacia (n = 5)). Diagnostic sensitivity and
      specificity were 96.5% [95% confidence interval (CI): 91.3-98.6%] and 100% [CI:
      97.5-100%] respectively. Background clearance and line intensities were good and
      very good. The RDT's test strip, not housed in a cassette, caused difficulties in
      manipulation and biosafety. The centrifugation step prescribed by the procedure
      challenged biosafety, but processing of 19 B. pseudomallei samples without
      centrifugation showed similar results for line intensity and background
      clearance, compared to centrifugation. The InBiOS RDT showed excellent accuracy
      for detection of B. pseudomallei in grown blood culture broth. Provided
      operational adaptations such as cassette housing, it has the potential to reduce
      time to diagnosis of melioidosis.

PMID- 29594801
TI  - Risk prediction in infective endocarditis by modified MELD-XI score.
AB  - The suitability of the model for end-stage liver disease excluding international
      normalized ratio (MELD-XI) score to predict adverse outcomes in infective
      endocarditis (IE) patients remains uncertain. This study was performed to explore
      the prognostic value of the MELD-XI score and modified MELD-XI score for patients
      with IE. A total of 858 patients with IE were consecutively enrolled and
      classified into two groups: MELD-XI <= 10 (n = 588) and MELD-XI > 10 (n = 270).
      Multivariate analysis was performed to determine risk factors independent of MELD
      XI score. Higher MELD-XI score was associated with higher in-hospital mortality
      (15.6 vs. 4.8%, p < 0.001) and major adverse clinical events (33.3 vs. 18.4%, p <
      0.001). MELD-XI score was an independent predictor of in-hospital death (odds
      ratio [OR] = 1.06, 95% CI, 1.02-1.10, p = 0.005). Based on a multivariate
      analysis, NYHA class III or IV (3 points), C-reactive protein > 9.5 mg/L (4
      points), and non-surgical treatment (6 points) were added to MELD-XI score.
      Modified MELD-XI score produced higher predictive power than previous (AUC 0.823
      vs. 0.701, p < 0.001). The cumulative incidence of long-term mortality (median 29
      months) was significantly higher in patients with modified MELD-XI score > 13
      than those without (log-rank = 25.30, p < 0.001). Modified MELD-XI score was
      independently associated with long-term mortality (hazard ratio = 1.08, 95% CI,
      1.04-1.12, p < 0.001). MELD-XI score could be used as a risk assessment tool in
      IE. Furthermore, modified MELD-XI score remained simple and more effective in
      predicting poor prognosis.

PMID- 29594803
TI  - Water-soluble MoS2 quantum dots are a viable fluorescent probe for hypochlorite.
AB  - A method is described for the fluorometric determination of hypochlorite. It is
      making use of molybdenum disulfide quantum dots (MoS2 QDs) as a fluorescent
      probe. The QDs are prepared by hydrothermal reaction of sodium molybdate with
      glutathione. They possess diameters typically ranging from 1.4 to 3.8 nm,
      excellent stability in water, and blue photoluminescence (with
      excitation/emission peaks located at 315/412 nm and a quantum yield of 3.7%). The
      fluorescence of the QDs is statically quenched by hypochlorite, and the Stern
      Volmer plot is linear. Hypochlorite can be detected in the 5-500 MUM
      concentration range with a 0.5 MUM detection limit. The method has been
      successfully applied to the determination of hypochlorite in spiked samples of
      tap water, lake water, and commercial disinfectants. Graphical abstract Schematic
      of a method for the fluorometric determination of hypochlorite using MoS2 quantum
      dots as a fluorescent probe. It has been applied to hypochlorite assay in spiked
      samples of tap water, lake water, and commercial disinfectants.

PMID- 29594802
TI  - Molecular strategy for the diagnosis of infectious lymphadenitis.
AB  - Molecular methods have been considered to be the gold standard for the diagnosis
      of infectious lymphadenitis. However, culture remains critical in the case of low
      bacterial concentrations. We used molecular assays and culture to examine fresh
      lymph node biopsies from patients with suspected infectious lymphadenopathy. We
      analyzed 1762 lymph node biopsies of which 522 (30%) samples were found positive
      by real-time PCR; the most commonly amplified bacteria were Bartonella henselae
      (n = 438, 84%), Francisella tularensis (n = 46, 9%), and Mycobacterium spp. (n =
      29, 6%). PCR amplification and sequencing of the 16S rDNA were positive for 359
      (20%) lymph node specimens including mainly B. henselae (n = 167, 47%),
      Staphylococcus spp. (n = 77, 21%), and Streptococcus spp. (n = 41, 11%). In
      total, 351 lymph nodes were cultured on agar plates and 77 (22%) were positive.
      Significantly more lymph nodes infected by Gram-positive easy-growing agents were
      diagnosed by culture (n = 45) than by 16S rDNA PCR (p = 0.02). Culture remains
      critical for the diagnosis of easy-growing bacteria and mycobacteria; clinicians
      should be aware that a negative molecular result does not imply absence of
      infection.

PMID- 29594804
TI  - A rapid colorimetric immunoassay for the detection of pathogenic bacteria on
      poultry processing plants using cotton swabs and nanobeads.
AB  - The work describes a simple cotton swab-based colorimetric immunoassay as a rapid
      screening tool for pathogenic bacteria on poultry processing plants. This
      immunosensing platform can be used for the detection of pathogens present on
      surfaces such as glass, stainless steel and chicken meat. Unlike the reported
      assays, here, cotton swab plays dual function: as a sample collector from the
      solid surfaces and as detection platform. The immunoassay was tested for the
      detection of 4 different bacteria; Salmonella typhimurium, Salmonella
      enteritidis, Staphylococcus aureus and Campylobacter jejuni. The immunoassays
      were fabricated by immobilizing specific antibody for each bacterium on a cotton
      swab that is used to recover the cells from contaminated surfaces. Then, a
      sandwich immunoassay was developed by immersing the cotton swab in different
      colored nanobead-conjugated antibody solutions which corresponds to different
      bacteria. The immunoassays response was detected colorimetrically by following
      the change in the color intensity produced by the nanobeads due to the specific
      binding on the cotton swab. This simple colorimetric assay is very sensitive with
      a detection limit of 10 cfu.mL-1. Furthermore, no significant cross reactivity of
      the immunoassays with non specific bacteria was observed indicating good
      selectivity of the immunoassays. This simple, disposable and easy-to- use
      colorimetric platform shows great promise as rapid qualitative and semi
      quantitative detection tool for microorganisms on food processing plants and
      other surfaces. Graphical abstract Schematic of the sandwich colorimetric
      immunosensor for the detection of pathogenic bacteria on poultry processing
      plants using cotton swabs and nanobeads.

PMID- 29594805
TI  - Porous Ni3N nanosheet array as a catalyst for nonenzymatic amperometric
      determination of glucose.
AB  - A glassy carbon electrode was modified with an array of porous Ni3N nanosheets
      (Ni3N NA) and studied for its use in non-enzymatic electrochemical detection of
      glucose. The morphology and structure of the Ni3N NA were characterized by
      scanning electron microscopy and X-ray diffraction. Electrochemical studies
      demonstrated that the Ni3N NA acts as an efficient catalyst for the electro
      oxidation of glucose at pH 13, best at a working voltage of 0.55 V (vs. Ag/AgCl).
      Figures of merit include (a) high sensitivity (39 MUA.mM-1.cm-2), (b) a low limit
      of detection (0.48 MUM), and (c) a linear range that extends from 2 MUM to 7.5
      mM. The sensor was applied to the determination of glucose levels in human serum,
      and satisfactory results were obtained. Graphical abstract Nonenzymatic
      electrochemical glucose sensor based on porous Ni3N nanosheet array. The arrow
      indicates the successive addition of glucose standard solutions.

PMID- 29594806
TI  - On the calculation of the potential of mean force between atomistic
      nanoparticles.
AB  - We study the potential of mean force (PMF) between atomistic silica and gold
      nanoparticles in the vacuum by using molecular dynamics simulations. Such an
      investigation is devised in order to fully characterize the effective
      interactions between atomistic nanoparticles, a crucial step to describe the PMF
      in high-density coarse-grained polymer nanocomposites. In our study, we first
      investigate the behavior of silica nanoparticles, considering cases corresponding
      to different particle sizes and assessing results against an analytic theory
      developed by Hamaker for a system of Lennard-Jones interacting particles (H.C.
      Hamaker, Physica A 4, 1058 (1937)). Once validated the procedure, we calculate
      effective interactions between gold nanoparticles, which are considered both bare
      and coated with polyethylene chains, in order to investigate the effects of the
      grafting density [Formula: see text] on the PMF. Upon performing atomistic
      molecular dynamics simulations, it turns out that silica nanoparticles experience
      similar interactions regardless of the particle size, the most remarkable
      difference being a peak in the PMF due to surface interactions, clearly apparent
      for the larger size. As for bare gold nanoparticles, they are slightly
      interacting, the strength of the effective force increasing for the coated cases.
      The profile of the resulting PMF resembles a Lennard-Jones potential for
      intermediate [Formula: see text], becoming progressively more repulsive for high
      [Formula: see text] and low interparticle separations.

PMID- 29594807
TI  - Genetic Polymorphisms in miR-146a, miR-196a2 and miR-125a Genes and its
      Association in Prostate Cancer.
AB  - The increase in incidence of prostate cancer in the Indian Population stresses
      the need to identify genetic markers for susceptibility and prognosis. Recent
      studies show that microRNAs play an important role in tumorigenesis by altering
      proliferation, differentiation and cell death. Gene polymorphisms not only in
      promoter region but also within miRNA gene have been shown to affect expression.
      The present study was aimed to analyze the role of miR-146a, miR-196a2 and miR
      125a gene polymorphisms in prostate cancer. Genotyping of three SNPs rs73318382,
      rs57095329, rs2910164 in miRNA146a, rs11614913 in miR-196a2 and rs41275794,
      rs12976445, rs10404453 and rs1297533 in miR-125a was performed in 100 cases and
      100 controls. Statistical analysis revealed the heterozygous AG genotype of the
      rs57095329 was significantly decreased in the cases when compared to the controls
      (OR-0.45, CI -0.24 to 0.85, p value-0.02) indicating an inverse association of
      this genotype with prostate cancer. Further the heterozygous CT of miR-196a2
      (rs11614913) (OR-1.88, CI-1.06 to 3.35, p-0.02) and homozygous CC of miR-125a
      (rs12976445) (OR-2.55, CI -1.15 to 4.65, p-0.03) showed increased risk for
      prostate cancer. Combined analysis of all the genotypes revealed that the
      haplotype combination AGGCGTGG (OR = 0.09 at CI 95% (0.01-0.65) showed an inverse
      association with prostate cancer. Stratified analysis based on the age and tumor
      grade revealed no significant association.

PMID- 29594809
TI  - Presence of the posterior pituitary bright spot sign on MRI in the general
      population: a comparison between 1.5 and 3T MRI and between 2D-T1 spin-echo- and
      3D-T1 gradient-echo sequences.
AB  - PURPOSE: To describe the prevalence of the posterior pituitary bright spot (PPBS)
      in the general population on 1.5 and 3T MRI examinations and on 2D-T1 spin-echo
      (SE) and 3D-T1 gradient-echo (GE) sequences. MATERIALS AND METHODS: 1017 subjects
      who received an MRI of the brain for aspecific neurological complaints were
      included. MRI was performed on 1.5T in 64.5% and on 3T in 35.5% of subjects.
      Presence of the PPBS was evaluated on sagittal 2D T1-SE echo images with slice
      thickness 3 mm in 67.5% and on sagittal 3D T1-GE with slice thickness 0.9 mm in
      32.5% of subjects. RESULTS: The PPBS was detectable in 95.9% of subjects. After
      correction for sex and age, no statistically significant difference could be seen
      concerning PPBS detection between 1.5 and 3T MRI examinations (p = 0.533), nor
      between 2D T1-SE and 3D T1-GE sequences (p = 0.217). There was a statistically
      significant association between increasing age and the absence of the PPBS (p <
      0.001). The PPBS could not be identified in 6.2% of male subjects, compared to
      2.2% of female subjects (p = 0.01). DISCUSSION: Absence of the PPBS can be seen
      in 4.1% of patients undergoing MRI of the brain for non-endocrinological reasons.
      Neither field-strength nor the use of a thick-sliced 2D T1-SE versus a thin
      sliced 3D T1-GE sequence influenced the detectability of the PPBS. There is a
      statistically significant association between increasing age and male sex and the
      absence of the PPBS.

PMID- 29594810
TI  - A sample-to-answer droplet magnetofluidic assay platform for quantitative
      methylation-specific PCR.
AB  - Dysregulation of DNA methylation has been identified as an epigenetic biomarker
      for numerous cancer types. Gene-specific identification techniques relying on
      methylation-specific PCR (MSP) require a lengthy manual benchtop process that is
      susceptible to human-error and contamination. This MSP assay requires a series of
      discrete sample processing steps including genomic DNA extraction, bisulfite
      conversion and readout via PCR. In this work, we present a streamlined assay
      platform utilizing droplet magnetofluidic principles for integration of all
      sample processing steps required to obtain quantitative MSP signal from raw
      biological samples. We present a streamlined protocol for solid-phase extraction
      and bisulfite conversion of genomic DNA, which minimizes reagent use and
      simplifies the sample preparation protocol for implementation on a compact assay
      platform. Furthermore, we present a thermally robust assay chip that enables DNA
      extraction, bisulfite conversion and quantitative PCR from biological samples on
      a single device. Technical improvements to facilitate DNA extraction and PCR on a
      single chip in addition to chip performance characterization data are presented.

PMID- 29594808
TI  - Stress Response Modulation Underlying the Psychobiology of Resilience.
AB  - PURPOSE OF REVIEW: This review focuses on the relationship between resilience and
      the ability to effectively modulate the stress response. Neurobiological and
      behavioral responses to stress are highly variable. Exposure to a similar
      stressor can lead to heterogeneous outcomes-manifesting psychopathology in one
      individual, but having minimal effect, or even enhancing resilience, in another.
      We highlight aspects of stress response modulation related to early life
      development and epigenetics, selected neurobiological and neurochemical systems,
      and a number of emotional, cognitive, psychosocial, and behavioral factors
      important in resilience. We also briefly discuss interventions with potential to
      build and promote resilience. RECENT FINDINGS: Throughout this review, we include
      evidence from recent preclinical and clinical studies relevant to the
      psychobiology of resilient stress response modulation. Effective modulation of
      the stress response is an essential component of resilience and is dependent on a
      complex interplay of neurobiological and behavioral factors.

PMID- 29594811
TI  - A regenerable sorbent composed of a zeolite imidazolate framework (ZIF-8), Fe3O4
      and graphene oxide for enrichment of atorvastatin and simvastatin prior to their
      determination by HPLC.
AB  - Graphene oxide (GO), nanosized Fe3O4 and zeolite imidazolate framework-8 (ZIF-8)
      were hybridized as a multifunctional sorbent for use in microextraction. The
      sorbent was characterized by SEM, TEM, XRD and FTIR. The composite is porous, has
      a high specific surface (> 600 m2.g-1) and is paramagnetic. The GO sheets are
      shown to act as carriers for the Fe3O4 nanoparticles and ZIF-8. The composite is
      a viable material for the preconcentration of atorvastatin and simvastatin from
      urine prior to their determination by HPLC with PDA detection. The limits of
      detection are 116 and 387 pg.mL-1, respectively. Recoveries from spiked urine
      samples range between 84.7 and 95.7%, with relative standard deviation of <=4.5%.
      Enrichment factors range from 169 to 191. The method was successfully applied to
      the determination of atorvastatin in urine. Moreover, this sorbent is regenerable
      and recyclable for at least seven times without obvious decrease in performance.
      Graphical abstract A composite sorbent composed of a zeolite imidazolate
      framework, Fe3O4 and graphene oxide was applied to the extraction of statins in
      urine prior their determination by HPLC.

PMID- 29594812
TI  - Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor of 30-Day Mortality of
      Intracerebral Hemorrhage Patients: a Validation Cohort Study.
AB  - In a previous study in patients with intracranial hemorrhage (ICH), we found an
      association between high neutrophil-to-lymphocyte ratio (NLR) with poor short
      term mortality. In the current study, this preliminary finding was validated
      using an independent patient cohort. A total of 181 ICH patients (from January
      2016 to December 2017) were included. Diagnosis was confirmed using computed
      tomography (CT) in all cases. Patient survival (up to 30 days) was compared
      between subjects with high NLR (above the 7.35 cutoff; n = 74) versus low NLR (<=
      7.35; n = 107) using Kaplan-Meier analysis. A multivariate logistic regression
      was performed to identify factors that influenced the 30-day mortality.
      Correlation between NLR with other relevant factors (e.g., C-reactive protein
      (CRP) and fibrinogen) was examined using Spearman correlation analysis. The 30
      day mortality was 19.3% (35/181) in the entire sample, 37.8% (28/74) in the high
      NLR group, and 6.5% (7/107) in the low-NLR group (P < 0.001). In comparison to
      the low-NLR group, the high-NLR group had higher rate of intraventricular
      hemorrhage (29.7 vs. 16.8%), ICH volume (median 23.9 vs. 6.0 cm3) and ICH score
      (median 1.5 vs. 0), and lower GCS score (9.4 +/- 4.5 vs. 12.9 +/- 3.2). An
      analysis that divided the samples into three equal parts based on NLR also showed
      increasing 30-day mortality with incremental NLR (1.6, 15.0, and 41.7% from
      lowest to highest NLR tertile, P for trend < 0.001). Kaplan-Meier curve showed
      higher 30-day mortality in subjects with high NLR than those with low NLR (P <
      0.001 vs. low-NLR group, log-rank test). High NLR (> 7.35) is associated with
      poor short-term survival in acute ICH patients.

PMID- 29594813
TI  - A hollow porous molecularly imprinted polymer as a sorbent for the extraction of
      7 macrolide antibiotics prior to their determination by HPLC-MS/MS.
AB  - A hollow porous molecularly imprinted polymer (HPMIP) is described for use in
      dispersive solid phase extraction of macrolide antibiotics (MACs). The HPMIP was
      prepared by using spiramycin as the template, methacrylic acid as the functional
      monomer, and mesoporous MCM-41 (Mobile Composition of Matter No. 41; with a size
      of about 100 nm) as a sacrificial support. The sorbent was characterized by
      Fourier transform infrared spectrometry, transmission electron microscopy,
      nitrogen adsorption and thermo-gravimetric analysis. Several parameters affecting
      the extraction efficiency were optimized. The material has a large surface area
      (359 m2.g-1), and most recognition sites are located on the surface of the
      HPMIPs. This results in high binding capacity (120 MUmol.g-1) and fast binding
      (20 min) in comparison to either MCM-41-core surface MIPs or solid MIPs. The
      method was applied to the extraction of the MACs azithromycin, spiramycin,
      tilmicosin, tylosin, clarithromycin, roxithromycin and josamycin from spiked
      honey. The recoveries, determined by HPLC-MS/MS, ranged from 88.0% to 117% at the
      three spiking levels tested (1, 5 and 20 MUg.kg-1). Intra-day and inter-day assay
      precision at three spiking levels are <10.7% (for n = 6) and 12.6% (n = 3),
      respectively. The limits of detection are between 3 and 17 ng.kg-1. This
      indicates the superiority of the method in selective extraction of macrolides
      even from complex matrices. Graphical abstract Hollow porous molecularly
      imprinted polymers using spiramycin as the template are shown to be viable
      dispersive solid phase extraction adsorbents for selective enrichment of
      macrolide antibiotics in honey products prior to their quantitation by HPLC
      MS/MS.

PMID- 29594814
TI  - Novel drugs for heart rate control in heart failure.
AB  - In patients with heart failure, increased sympathetic activity is associated with
      a positive chronotropic stimulation leading to accelerated resting heart rate.
      Elevated heart rate (HR) is a risk factor for cardiovascular events, both in the
      general population and in patients with heart failure. Ivabradine is a pure HR
      lowering agent, and it does not affect myocardial contractility, blood pressure,
      intracardiac conduction, or ventricular repolarization. In clinical trials such
      as BEAUTIFUL, CARVIVA HF, SHIFT, and INTENSIFY in patients with systolic left
      ventricular dysfunction, heart rate reduction with ivabradine brought positive
      outcomes. However, the results of the recent meta-analysis are rather neutral. In
      a diabetes mouse model of heart failure with preserved ejection fraction (HFpEF),
      selective heart rate reduction by If inhibition improved vascular stiffness, left
      ventricular (LV) contractility, and diastolic function. However, EDIFY (Effect of
      ivabradine in patients with heart rate with preserved ejection fraction) trial
      show that the use of ivabradine in patients with HFpEF is not supported. The
      further clinical trials investigating the use of ivabradine in heart failure
      should be carried out.

PMID- 29594815
TI  - Has time come for the use of direct oral anticoagulants in the extended
      prophylaxis of venous thromboembolism in acutely ill medical patients? No.
AB  - Acutely ill hospitalized medical patients are at high risk of venous
      thromboembolism (VTE). Although thromboprophylaxis in these patients is
      recommended since 2004 by the American College of Chest Physicians, it is widely
      underused. The doubt as to whether or not to treat patients at high VTE risk
      after hospital discharge came from the knowledge that this risk may persist after
      the hospital admission period. Two meta-analyses comparing extended- versus short
      duration prophylaxis are published. The results demonstrate an unfavorable
      balance between VTE prevention and incidence of major bleeding in patients
      assigned to extended-duration thromboprophylaxis. Only in the APEX study,
      betrixaban, a direct inhibitor of factor Xa, shows similar efficacy and safety
      compared to enoxaparin. However, while it is very promising, oral anticoagulant
      phase III studies and post-marketing registers are lacking. Moreover, betrixaban
      has a long half-life, an excretion in the gut by means of P-glycoprotein, and the
      lack of an antidote. These characteristics and the meta-analysis results prompt
      us to answer no to the extended thromboprophylaxis in hospitalized medical
      patients, at least now.

PMID- 29594816
TI  - Drug-eluting stents vs. bare metal stents in elderly patients.

PMID- 29594817
TI  - Highlights from the scientific and educational abstracts presented at the ASER
      2017 annual scientific meeting and postgraduate course.
AB  - The annual meeting of the American Society of Emergency Radiology (ASER) took
      place in Toronto, Canada, on September 6 through September 9, 2017. Attendees
      represented the USA as well as international emergency radiology communities,
      including those from academic, private practice, and teleradiology settings.
      There were several "members in training" in attendance as well. The meeting again
      featured the "Trauma Head to Toe" 2-day didactic course, highlighting various
      important topics on imaging of traumatic injuries. Scattered throughout the 4
      days were several poster and case of the day presentations, scientific sessions,
      and self-assessment modules. The following is a summary of the educational
      posters and scientific papers.

PMID- 29594818
TI  - Improved peroxidase mimetic activity of a mixture of WS2 nanosheets and silver
      nanoclusters for chemiluminescent quantification of H2O2 and glucose.
AB  - It is reported that a mixture of WS2 nanosheets (WS2 NS) and silver nanoclusters
      (AgNCs) displays strongly enhanced peroxidase-mimicking activity. The catalytic
      effect of the mixture was studied by colorimetry, fluorometry, chemiluminescence
      (CL) and electrochemistry. The effect is interpreted in terms of a difference
      between the Fermi energy level of the two nanomaterials. This leads to the
      formation of charge separation regions which act as active sites for enzyme
      mimetic interaction with the substrates. The mixture of WS2 NS and AgNCs was
      exploited for the non-enzymatic determination of H2O2 and glucose. A stopped-flow
      method was applied as a sensitive CL detection system using the bicarbonate-H2O2
      reaction. The mixture has a powerful peroxidase mimicking activity on the
      bicarbonate-H2O2 CL reaction, and this effect is much larger than that of any
      single constituent. In addition, the CL emission is improved several times by
      using the stopped-flow technique. Under optimum condition, H2O2 can be determined
      in the 2.5-1500 nM concentration range. Moreover, glucose levels in human serum
      can be quantified via glucose oxidase based oxidation which leads to the
      generation of H2O2. Using this CL assay, a linear relationship was obtained
      between the intensity of the CL emission and glucose concentration in the range
      of 0.03-20 MUM, with a limit of detection (3S) of 13 nM. Graphical abstract An
      enhanced peroxidase-like catalytic activity for WS2 nanosheets (WS2 NS) was
      revealed in the presence of silver nanoclusters (AgNCs), and was exploited for
      the non-enzymatic determination of H2O2, and of glucose (via glucose oxidase;
      GOx) using a stopped-flow CL method.

PMID- 29594819
TI  - Prospective evaluation of serum IL-16 and risk of prostate cancer in the
      Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
AB  - BACKGROUND: Sexually transmitted infections and chronic inflammation have been
      associated with an increased risk of prostate cancer. Inflammatory mediators,
      such as cytokines and free radicals, have been hypothesized to play a role.
      METHODS: To explore the role of inflammation in prostate cancer risk further, we
      examined the association between pre-diagnostic serum levels of interleukin-16
      (IL-16), an important pleiotropic cytokine, and prostate cancer risk among 932
      Caucasian cases and 942 controls and 154 African-American cases and 302 controls
      in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum IL
      16 was quantified using enzyme-linked immunoassay. Logistic regression was used
      to estimate associations between IL-16 and prostate cancer risk, separately by
      race. RESULTS: Although no association between IL-16 and prostate cancer overall
      was observed among Caucasians (p = 0.27), a significantly increased risk of high
      grade prostate cancer, defined as Gleason >= 7 (phet = 0.02), was observed with
      increasing levels of IL-16 (OR3rd vs. 1st tertile = 1.37, 95% CI 1.04-1.81,
      ptrend = 0.02). We also discovered a significant interaction between IL-16 and
      history of gonorrhea (p = 0.04). Among Caucasian men with a history of gonorrhea,
      elevated IL-16 levels were associated with an increased risk of prostate cancer
      (OR3rd vs. 1st tertile = 3.64, 95% CI 1.14-11.6) but no association was seen
      among those without a history of gonorrhea (OR3rd vs. 1st tertile = 1.06, 95% CI
      0.83-1.34). No associations were observed among African-Americans. CONCLUSIONS:
      This study found evidence that higher pre-diagnostic IL-16 levels may be
      associated with increased risk of high-grade disease, supporting inflammation as
      potential mechanism by which sexually transmitted diseases may increase risk.

PMID- 29594820
TI  - Prospective multicenter non-randomized controlled study on intraosseous stability
      and healing period for dental implants in the posterior region.
AB  - BACKGROUND: A current implant body surface was treated with "rough processing" by
      sandblasting and acid etching for the purposes of obtaining more reliable
      osseointegration and shortening the treatment period. Various reports have
      examined the healing period with the use of these implant bodies, but a consensus
      opinion has not yet been obtained. The purpose of this study is to evaluate the
      relationship between insertion torque (IT) and implant stability quotient (ISQ)
      at implant treatment using the current rough-surfaced implant. We evaluated the
      implant treatment sites with ISQ values, IT values, and voxel values. METHODS:
      Participants in this study comprised 26 patients (10 males, 16 females; mean age,
      55.5 years) who received posterior region dental implants at Tokyo Dental College
      Hospital or Fukuoka Dental College Hospital. For all participants, pretreatment
      computed tomography and determination of bone quality from voxel values were
      performed. Thirty-two implant bodies were inserted into the posterior region, and
      insertion torque was measured. ISQ was also measured at 0, 2, 4, 6, 8, and 12
      weeks postoperatively. RESULTS: Eight implant bodies in the maxilla and 24 in the
      mandible were inserted. All ISQ values increased, exceeding 60 by 6 weeks
      postoperatively. For insertion torque < 30 N cm, ISQ increased significantly
      after 8 weeks. For >= 30 N cm, the ratio at which high ISQ values appeared
      increased significantly after 6 weeks. Compared with the treatment area with
      insertion torque < 40 N cm, the treatment area >= 40 N cm showed a significantly
      higher voxel value. CONCLUSIONS: No significant relationship was found between
      the insertion torque value and the ISQ value. Also, it was suggested that the ISQ
      value was considered to be an important indicator for observing the treatment
      state of the implant.

PMID- 29594821
TI  - Tree nut, peanut, and peanut butter consumption and the risk of gastric and
      esophageal cancer subtypes: the Netherlands Cohort Study.
AB  - BACKGROUND: Nut consumption has been associated with reduced cancer-related
      mortality. However, it is unclear whether nut consumption also reduces the risk
      of esophageal and gastric cancer subtypes. We prospectively investigated the
      relationship of tree nut, peanut, and peanut butter intake with risk of
      esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC),
      gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA)
      in the Netherlands Cohort Study. METHODS: In 1986, 120,852 males and females,
      aged 55-69 years, completed a baseline questionnaire on diet and cancer risk
      factors. After 20.3 years of follow-up, 133 ESCC, 200 EAC, 191 GCA, and 586 GNCA
      cases, and 3,720 subcohort members were available for multivariable Cox
      regression analyses, using a case-cohort approach. RESULTS: Increased total nut
      consumption was significantly associated with a decreased risk of ESCC and GNCA
      [HRs (95% CIs) for 10 + g/day vs. nonconsumers = 0.54 (0.30-0.96) and 0.73 (0.55
      0.97), respectively], but not with EAC and GCA risk. Similar trends were observed
      for tree nut and peanut intake, which were mostly nonsignificant. For peanut
      butter intake, no significant associations were found. When excluding the first
      four years of follow-up to reduce the possible influence of reversed causation,
      the relation between nut consumption and ESCC risk attenuated, but remained
      inverse. CONCLUSIONS: Our findings suggest that increased tree nut and peanut
      consumption is inversely associated with GNCA risk and possibly with ESCC risk,
      but not with the risk of the other esophageal and gastric cancer subtypes.

PMID- 29594822
TI  - Sicilian centenarian offspring are more resistant to immune ageing.
AB  - BACKGROUND: Immunosenescence constitutes a major indirect cause of morbidity and
      mortality in the elderly. Previous analysis of immune signatures in a cohort of
      centenarian offspring showed an intermediate immunophenotype between age-matched
      and younger controls. AIMS: To confirm and extend the previous studies performing
      further phenotypical analysis in centenarian offspring and controls. METHODS:
      Analysis of Treg cells, gammadelta T cells, mucosal-associated invariant T cells,
      and senescent immune T cells was performed in centenarian offspring and controls.
      RESULTS: We report significant differences between elderly and centenarian
      offspring in most of the studied subsets, showing that centenarian offspring
      subsets present an intermediate phenotyping between elderly and younger people.
      CONCLUSION: The whole present data confirm and extend the previous results
      showing that centenarian offspring retain more youthful immunological parameters
      and that the exhaustion of the immune system is less evident than in elderly
      without centenarian parents, though further investigations are warranted.

PMID- 29594823
TI  - Estimation of reduced walking speed using simple measurements of physical and
      psychophysiological function in community-dwelling elderly people: a cross
      sectional and longitudinal study.
AB  - BACKGROUND: Early detection of reduced mobility function is important in elderly
      people. Usual walking speed is useful to assess mobility function, but is often
      not feasible in a community setting. AIMS: This study aimed to explore a simple
      surrogate indicator of usual walking speed in elderly people. METHODS: The
      participants were 516 community-dwelling elderly people. As a baseline survey,
      the usual walking speed and candidates of surrogate indicators including physical
      function and psychophysiological function were measured. After 2 years, the
      occurrence of mobility limitation was assessed. RESULTS: In cross-sectional
      analysis, a linear regression model with maximum step length, age, and sex
      presented the most favourable adjusted R2 of 0.426 for estimating usual walking
      speed. Maximum step length (MSL) also showed good predictive accuracy for usual
      walking speed < 0.8 m/s {area under the curve [AUC] 0.908 [95% confidence
      interval (CI) 0.811, 1.000]} and < 1.0 m/s [AUC 0.883 (95% CI) 0.832, 0.933)] in
      receiver-operating characteristic (ROC) analysis. In longitudinal analysis, the
      predictive accuracy of MSL for mobility limitation [AUC 0.813 (95% CI 0.752,
      0.874)] was similar to that of usual walking speed [AUC 0.808 (95% CI 0.747,
      0.869)] in ROC analysis. CONCLUSIONS AND DISCUSSION: The results of this study
      suggest that MSL may serve as a simple surrogate indicator of UWS in elderly
      people.

PMID- 29594824
TI  - Generalizing Gillespie's Direct Method to Enable Network-Free Simulations.
AB  - Gillespie's direct method for stochastic simulation of chemical kinetics is a
      staple of computational systems biology research. However, the algorithm requires
      explicit enumeration of all reactions and all chemical species that may arise in
      the system. In many cases, this is not feasible due to the combinatorial
      explosion of reactions and species in biological networks. Rule-based modeling
      frameworks provide a way to exactly represent networks containing such
      combinatorial complexity, and generalizations of Gillespie's direct method have
      been developed as simulation engines for rule-based modeling languages. Here, we
      provide both a high-level description of the algorithms underlying the simulation
      engines, termed network-free simulation algorithms, and how they have been
      applied in systems biology research. We also define a generic rule-based modeling
      framework and describe a number of technical details required for adapting
      Gillespie's direct method for network-free simulation. Finally, we briefly
      discuss potential avenues for advancing network-free simulation and the role they
      continue to play in modeling dynamical systems in biology.

PMID- 29594825
TI  - Modeling the Effect of Mucin Binding in the Gut on Drug Delivery.
AB  - An important part the absorption, distribution, metabolism and excretion of an
      oral therapeutic is the flux rate of drug compound crossing the mucus lining of
      the gut. To understand this part of the absorption process, we develop a
      mathematical model of advection, diffusion and binding of drug compounds within
      the mucus layer of the intestines. Analysis of this model yields simple,
      measurable criteria for the successful mucin layer traversal of drug compound.

PMID- 29594826
TI  - Sodium hypochlorite penetration into dentinal tubules after manual dynamic
      agitation and ultrasonic activation: a histochemical evaluation.
AB  - The aim of this study was to compare the effects of Manual Dynamic Agitation and
      Passive Ultrasonic Irrigation on sodium hypochlorite (NaOCl) penetration into
      dentinal tubules using its bleaching ability. Thirty-four single-rooted teeth
      with round-shaped root canals were distributed in two homogeneous groups and one
      control group, characterized by different NaOCl activation systems: Manual
      Dynamic Agitation and Passive Ultrasonic Irrigation. After instrumentation, all
      root canals were stained with 10% copper sulphate solution followed by 1%
      rubeanic acid alcohol solution under vacuum. Final irrigation was performed with
      5 mL of 5.25% NaOCl solution for 1 min and activated with Manual Dynamic
      Agitation or Passive Ultrasonic Irrigation for another 1 min depending on the
      treatment group. The teeth were transversely sectioned at the middle portion of
      the apical, middle, and coronal thirds and observed under light microscope. NaOCl
      solution penetration was evaluated by measuring the percentage of bleached
      circumference of the root canal relative to the stained circumference, bleached
      areas, mean, and maximum penetration depth. No differences in the evaluated
      parameters were observed between groups (p > 0.05). Within groups, an increase of
      values was recorded from apical to coronal direction as for percentage of
      staining, percentage of bleaching and bleached area. NaOCl penetration into
      dentinal tubules did not significantly vary among the three levels. No
      significant differences in penetration of sodium hypochlorite into dentinal
      tubules when activated by means of Manual Dynamic Agitation or Passive Ultrasonic
      Irrigation were observed in the apical, middle, and coronal thirds of teeth with
      single straight round root canals.

PMID- 29594827
TI  - Cytotoxic and biological effects of bulk fill composites on rat cortical neuron
      cells.
AB  - The aim of this study was to investigate potential cellular responses and
      biological effects of new generation dental composites on cortical neuron cells
      in two different exposure times. The study group included five different bulk
      fill flow able composites; Surefil SDR Flow, X-tra Base Flow, Venus Bulk Flow,
      Filtek Bulk Flow and Tetric-Evo Flow. They were filled in Teflon molds (Height: 4
      mm, Width: 6 mm) and irradiated for 20 s. Cortical neuron cells were inoculated
      into 24-well plates. After 80% of the wells were coated, the 3 um membrane was
      inserted and dental filling materials were added. The experiment was continued
      for 24 and 72 h. Cell viability measured by MTT assay test, total antioxidant and
      total oxidant status were examined using real assay diagnostic kits. The patterns
      of cell death (apoptosis) were analyzed using annexin V-FITC staining with flow
      cytometry. Beta-defensins were quantitatively assessed by RT-PCR. IL-6, IL-8 and
      IL-10 cytokines were measured from the supernatants. All composites significantly
      affected analyses parameters during the exposure durations. Our data provide
      evidence that all dental materials tested are cytotoxic in acute phase and these
      effects are induced cellular death after different exposure periods. Significant
      cytotoxicity was detected in TE, XB, SS, FBF and VBF groups at 24 and 72 h,
      respectively.

PMID- 29594828
TI  - Zwitterion-functionalized polymer microspheres as a sorbent for solid phase
      extraction of trace levels of V(V), Cr(III), As(III), Sn(IV), Sb(III) and Hg(II)
      prior to their determination by ICP-MS.
AB  - This paper describes the preparation of zwitterion-functionalized polymer
      microspheres (ZPMs) and their application to simultaneous enrichment of V(V),
      Cr(III), As(III), Sn(IV), Sb(III) and Hg(II) from environmental water samples.
      The ZPMs were prepared by emulsion copolymerization of ethyl methacrylate, 2
      diethylaminoethyl methacrylate and triethylene glycol dimethyl acrylate followed
      by modification with 1,3-propanesultone. The components were analyzed by
      elemental analyses as well as Fourier transform infrared spectroscopy, and the
      structures were characterized by scanning electron microscopy and transmission
      electron microscopy. The ZPMs were packed into a mini-column for on-line solid
      phase extraction (SPE) of the above metal ions. Following extraction with 40 mM
      NH4NO3 and 0.5 M HNO3 solution, the ions were quantified by ICP-MS. Under the
      optimized conditions, the enrichment factors (from a 40 mL sample) are up to 60
      for the ions V(V), As(III), Sb(III) and Hg(II), and 55 for Cr(III) and Sn(IV).
      The detection limits are 1.2, 3.4, 1.0, 3.7, 2.1 and 1.6 ng L-1 for V(V),
      Cr(III), As(III), Sn(IV), Sb(III) and Hg(II), respectively, and the relative
      standard deviations (RSDs) are below 5.2%. The feasibility and accuracy of the
      method were validated by successfully analyzing six certified reference materials
      as well as lake, well and river waters. Graphical abstract Zwitterion
      functionalized polymer microspheres (ZPMs) were prepared and packed into a mini
      column for on-line solid-phase extraction (SPE) via pump 1. Then V(V), Cr(III),
      As(III), Sn(IV), Sb(III) and Hg(II) ions in environmental waters were eluted and
      submitted to ICP-MS via pump 2.

PMID- 29594829
TI  - Autism spectrum disorders are prevalent among patients with dystrophinopathies.
AB  - Recent studies have reported a higher prevalence of autism spectrum disorders
      among patients with dystrophinopathies. The aim of this study was to investigate
      the prevalence of autism spectrum disorder (ASD) among those with
      dystrophinopathies. The possible role of dystrophin isoforms in patients was also
      explored. Fifty-six patients recruited from Toneyama National Hospital were
      included in this study (mean age = 12.9 years, SD = 5.2 years). Autistic symptoms
      were evaluated using the Pervasive Developmental Disorders/Autism Spectrum
      Disorders Rating Scale (PARS), a clinician rating scale. Eleven patients (19.6%;
      95% confidence interval 10.2-32.4) met the criteria for ASD based on their PARS
      scores. Patients were separated into two groups based on the cumulative loss of
      dystrophin isoforms predicted from the mutation location. The prevalence of ASD
      was examined between these groups. Infantile and current autistic symptoms did
      not differ between the groups, except on one subscale of the PARS. This study
      revealed that there was a high prevalence of ASD in patients with
      dystrophinopathies.

PMID- 29594830
TI  - The effects of Vibro-medical insole on vibrotactile sensation in diabetic
      patients with mild-to-moderate peripheral neuropathy.
AB  - Peripheral sensory neuropathy seems to be the main risk factor for diabetic foot
      ulceration. Previous studies demonstrated that stochastic resonance can improve
      the vibrotactile sensation of diabetic patients. The aim of this study was to
      evaluate the effects of Vibro-medical insole on pressure and vibration sensation
      in diabetic patients with mild-to-moderate peripheral neuropathy. A total of 20
      patients with mild-to-moderate diabetic neuropathy were included in the pre-test
      and post-test clinical trial study. Vibro-medical insole consists of medical
      insole and vibratory system. Medical insole was made independently for each
      participant and vibratory system was inserted in it. Pressure and vibration
      sensation were evaluated before and after 30-min walking with Vibro-medical
      insole. Semmes-Weinstein monofilaments and tuning fork were used to evaluate
      pressure and vibration sensation, respectively. Pressure sensation showed
      significantly improvement using Vibro-medical insole at the heel, first and fifth
      metatarsophalangeal heads, and hallux of both feet in all participants (p <
      0.001). Vibration sensation also improved at the big toe of both feet with 256 Hz
      tuning fork (p < 0.05) but no statistically significant effect was found with 128
      Hz tuning fork (p > 0.05). Vibro-medical insole significantly improved pressure
      and vibration sensation of the foot in diabetic patients with mild-to-moderate
      peripheral neuropathy. The results suggest that Vibro-medical insole can be used
      for daily living activities to overcome sensory loss in diabetic neuropathy
      patients.

PMID- 29594832
TI  - The remains at Lethbridge's Pocket - the case against the Kenniff brothers.
AB  - On 30th March 1902 Police Constable George Doyle and Carnarvon Station manager
      Albert Dahlke were allegedly gunned down at Lethbridge's Pocket in Central
      Queensland. Approximately 90 kg of ash and burnt human remains with articles
      belonging to the two men were later found in saddle bags left at the scene on a
      police horse. Subsequently two local cattle and horse thieves, Patrick and James
      Kenniff, were convicted in the Queensland Supreme Court of the wilful murder of
      Constable Doyle. Patrick was executed by hanging on 12th January 1903 and James
      had his sentence reduced to life imprisonment with hard labor. A number of
      irregularities were subsequently raised about the trial including the use of a
      "special" jury and the reliability of evidence from a witness who did not
      actually see the event. Forensic issues to be explored involve the accuracy of
      the descriptions of the carbonized material, whether the remains were actually
      those of Doyle and Dahlke, and whether the victims were dismembered before
      burning, as was alleged by the prosecution.

PMID- 29594831
TI  - Neurology and the Internet: a review.
AB  - Nowadays, the Internet is the major source to obtain information about diseases
      and their treatments. The Internet is gaining relevance in the neurological
      setting, considering the possibility of timely social interaction, contributing
      to general public awareness on otherwise less-well-known neurological conditions,
      promoting health equity and improving the health-related coping. Neurological
      patients can easily find several online opportunities for peer interactions and
      learning. On the other hand, neurologist can analyze user-generated data to
      better understand patient needs and to run epidemiological studies. Indeed,
      analyses of queries from Internet search engines on certain neurological diseases
      have shown a strict temporal and spatial correlation with the "real world." In
      this narrative review, we will discuss how the Internet is radically affecting
      the healthcare of people with neurological disorders and, most importantly, is
      shifting the paradigm of care from the hands of those who deliver care, into the
      hands of those who receive it. Besides, we will review possible limitations, such
      as safety concerns, financial issues, and the need for easy-to-access platforms.

PMID- 29594833
TI  - Palatal Polymorphous Adenocarcinoma with High-Grade Transformation: A Case Report
      and Literature Review.
AB  - Polymorphous adenocarcinoma (PAC) is the second most common intraoral malignant
      neoplasm of the minor salivary glands. However, it is very rare for PAC to show
      high-grade transformation (HGT) and to our knowledge, the English literature only
      seven reported cases. HGT tends to be observed when PAC recurs, and it is
      extremely rare to be seen at initial presentation. Here we report a 43-year-old
      Japanese male patient with PAC of the right palate showing HGT at initial
      presentation. Histopathologically, the tumor was characterized by a prominent
      solid and papillary-cystic growth pattern, with nuclear atypia and necrosis in
      area of HGT. The immunohistochemical staining pattern was consistent with PAC, as
      the tumor cells showed diffuse positivity for cytokeratin, vimentin and S-100,
      and focal positivity for bcl-2, alpha-SMA and EMA. The tumor cells in HGT areas
      were markedly positive for AR and Ki-67 (about 40%/HPF), and also focally
      positive for cyclin D1 and p53, whereas HER2/neu, ER, PgR, p63, D2-40, GCDFP-15,
      and mitochondria were negative. Here we present a very rare case of palatal PAC
      with HGT at initial presentation.

PMID- 29594834
TI  - Response surface methodology (RSM) modeling to improve removal of ciprofloxacin
      from aqueous solutions in photocatalytic process using copper oxide nanoparticles
      (CuO/UV).
AB  - Ciprofloxacin (CIP) antibiotic is considered as an emerging and biological
      resistant pollutant. This study aimed to improve of the removal of CIP from
      synthetic aqueous solutions in photocatalytic process through copper oxide
      nanoparticles as catalyst (CuO/UV). The effect of CIP concentration (10-200
      mg/l), catalyst dosage included CuO (0.01-0.1 g/l) and pH (3-11) as independent
      variables on the COD removal efficiency as response in photocatalytic process
      using UV-C lamps with three different powers of 8, 15 and 30-W were optimized
      through the central composite design in response surface method using design
      expert software. A second order model was selected as the best model with R2
      values and lack of fit as 0.85 and 0.06 for lamp 8-W, 0.89 and 0.11 for lamp 15
      W, and 0.86 and 0.19 for lamp 30-W, respectively. Optimum conditions were
      obtained in CIP concentration of 11.2 (mg/l), CuO dosage of 0.08 (g/l), and pH
      value of 8.17. In this condition, predicted maximum COD removal was respectively
      found 83.79, 93.18, and 98.90% for lamps 8, 15 and 30-W. According to the
      results, photocatalytic process using copper oxide nanoparticles can effectively
      compose CIP in aqueous solutions.

PMID- 29594835
TI  - Cu x O@DNA sphere-based electrochemical bioassay for sensitive detection of Pb2.
AB  - The paper describes a one-step synthetic method to chemically reduce cupric
      sulfate by ascorbic acid in the presence of DNA strands to directly produce Cu x
      O@DNA spheres. The DNA strands act as template to assist the preparation of Cu x
      O, and also are capable of specifically binding  Pb(II) ions. The Cu x O@DNA
      spheres possess high specific surface area and strong bioaffinity. They can be
      directly employed as platform for detecting Pb2+ sensitively. Electrochemical
      impedance spectroscopy data showed that the assay exhibits high sensitivity and a
      wide linear analytical range that extends from 0.1 to 100 nM, and the detection
      limit is 6.8 pM at a signal-to-noise ratio of 3. The assay is selective,
      acceptably reproducible, stable, and well feasible for the detection of Pb2+ in
      blood serum. Graphical abstract Schematic presentation of the preparation of DNA
      templated Cu x O spheres (Cu x O@DNA) for use in electrochemical detection of
      Pb2+. The assay exhibits detection limit of 6.8 pM, high selectivity, acceptable
      reproducibility, stability, and good applicability for Pb2+ detection.

PMID- 29594836
TI  - Molecular dynamics characterization of the SAMHD1 Aicardi-Goutieres Arg145Gln
      mutant: structural determinants for the impaired tetramerization.
AB  - Aicardi-Goutieres syndrome, a rare genetic disorder characterized by
      calcification of basal ganglia, results in psychomotor delays and epilepsy states
      from the early months of children life. This disease is caused by mutations in
      seven different genes encoding proteins implicated in the metabolism of nucleic
      acids, including SAMHD1. Twenty SAMHD1 gene variants have been discovered and in
      this work, a structural characterization of the SAMHD1 Aicardi-Goutieres
      Arg145Gln mutant is reported by classical molecular dynamics simulation. Four
      simulations have been carried out and compared. Two concerning the wild-type
      SAMHD1 form in presence and absence of cofactors, in order to explain the role of
      cofactors in the SAMHD1 assembly/disassembly process and, two concerning the
      Arg145Gln mutant, also in presence and absence of cofactors, in order to have an
      accurate comparison with the corresponding native forms. Results show the
      importance of native residue Arg145 in maintaining the tetramer, interacting with
      GTP cofactor inside allosteric sites. Replacement of arginine in glutamine gives
      rise to a loosening of GTP-protein interactions, when cofactors are present in
      allosteric sites, whilst in absence of cofactors, the occurrence of intra and
      inter-chain interactions is observed in the mutant, not seen in the native
      enzyme, making energetically unfavourable the tetramerization process.

PMID- 29594837
TI  - Diagnosing pituitary adenoma in unstained sections based on multiphoton
      microscopy.
AB  - PURPOSE: If we can find a new method that can achieve rapid diagnosis of adenoma
      during operation, it will help surgeon shorten the operation time and enhance the
      treatment efficacy. This study discusses the feasibility of multiphoton
      microscopy (MPM) in diagnosing pituitary adenoma. METHOD: MPM, based on two
      photon excited fluorescence (TPEF) and second harmonic generation (SHG) is
      performed for the diagnosis of pituitary adenoma in unstained sections. RESULTS:
      Our results show that MPM can reveal the variation of reticulin fiber by SHG
      signals of collagen, combined with the measurement of area of acinus, thickness
      of collagen fiber and collagen percentage. MPM can further reflect the change of
      meshwork in normal pituitary and hyperplasia quantitatively. And the
      characteristics of typical growth patterns of pituitary adenoma are demonstrated
      by the overlay of SHG and TPEF images. What's more, we can identify the boundary
      of normal pituitary, hyperplasia and adenoma from MPM images. And the experiment
      also results verify the feasibility of this method in frozen sections.
      CONCLUSION: These results indicated that MPM can make a diagnosis of pituitary
      adenoma by the morphological changes without routine pathological processing
      including hematoxylin-eosin (H&E) staining and other special staining. Therefore,
      this technique is expected to help diagnosis of pituitary adenoma during
      operation.

PMID- 29594838
TI  - The relation between retrobulbar blood flow and posterior ocular changes measured
      using spectral-domain optical coherence tomography in patients with obstructive
      sleep apnea syndrome.
AB  - PURPOSE: To investigate the effect of posterior ocular hemodynamics on the
      retinal nerve fiber layer (RNFL), choroid thickness (CT) and central macular
      thickness (CMT) in patients with obstructive sleep apnea syndrome (OSAS) and to
      reveal the association with glaucomatous optic neuropathy. METHODS: The research
      was planned as a prospective, randomized study. The ophthalmic, retinal and
      posterior ciliary artery pulsatile index (PI) and resistive index (RI) were
      measured by colored Doppler sonography. RNFL thickness, CMT and CT were then
      measured by spectral-domain optical coherence tomography. RESULTS: Sixty subjects
      were divided into four groups-mild, moderate and severe OSAS and a control group.
      There were 16 subjects in the control group, 14 in the mild OSAS group, 15 in the
      moderate OSAS group and 15 in the severe OSAS group. Ophthalmic artery and
      central retinal artery PI and RI values of the OSAS patients did not show
      statistically significant difference than those of the control group, but
      posterior ciliary artery (PCA) PI and RI values were significantly higher. In
      addition, mean, superior and inferior RNFL thickness values were significantly
      lower than those in the control group. Moreover, the glaucoma prevalence of the
      OSAS patients in this study was 6.8% and all of these patients were in the severe
      OSAS group. CONCLUSION: PI and RI values of the PCA, which supplies the optic
      nerve, show a linear increase as the apnea hypoxia index values in OSAS. As the
      grade of OSAS improves, this situation leads to a more serious ischemic optic
      neuropathy. Furthermore, the prevalence of glaucoma in this study is found to be
      higher in the severe OSAS group.

PMID- 29594840
TI  - Cytotoxic isocoumarin derivatives from the mangrove endophytic fungus Aspergillus
      sp. HN15-5D.
AB  - Five isocoumarin derivatives including three new compounds, aspergisocoumrins A-C
      (1-3), together with two known analogues, 8-dihydroxyisocoumarin-3-carboxylic
      acid (4) and dichlorodiaportin (5) were obtained from the culture of the
      endophytic fungus Aspergillus sp. HN15-5D derived from the fresh leaves of the
      mangrove plant Acanthus ilicifolius. Their structures were elucidated using
      comprehensive spectroscopic methods. The double bond geometry of compounds 1 and
      2 were assigned as E and Z on the basis of the distinct coupling constants,
      respectively. Compounds 1 and 2 showed cytotoxicity against MDA-MB-435 with IC50
      values of 5.08 +/- 0.88 and 4.98 +/- 0.74 MUM, respectively.

PMID- 29594841
TI  - A two-wavelength fluorescence recovery method for the simultaneous determination
      of aureomycin and oxytetracycline by using gold nanocrystals modified with serine
      and 11-mercaptoundecanoic acid.
AB  - A method is described for rapid (1 h) synthesis of gold nanoclusters (AuNCs) co
      functionalized with serine and 11-mercaptoundecanoic acid. The co-functionalized
      AuNCs exhibit good stability towards temperature, pH values, and over time. They
      were characterized by atomic force microscopy, high-resolution transmission
      electron microscopy, dynamic light scattering, and by fluorescence, IR and X-ray
      photoelectron spectroscopies. The fluorescence of the AuNCs is quenched by Hg(II)
      and restored on subsequent addition of aureomycin (CTC) or oxytetracycline (OTC).
      A fluorescent turn-on assay was worked out for simultaneous detection of CTC and
      OTC based on recording the change of the restored fluorescence measured at 420
      and 500 nm under 340 nm photoexcitation. The detection limits are 20 and 9 nM for
      CTC and OTC, respectively. The concentrations of CTC and OTC can also be
      visualized by UV illumination. The nanoprobe was successfully applied to the
      simultaneous determination of CTC and OTC in spiked human urine. Graphical
      abstract Schematic of a two-wavelength fluorescence recovery method for the
      simultaneous determination of aureomycin and oxytetracycline. It is based on the
      use of gold nanocrystals modified with serine and 11-mercaptoundecanoic acid, and
      on recording the change of the restored fluorescence measured at 420 and 500 nm.

PMID- 29594839
TI  - O-GlcNAc in cancer: An Oncometabolism-fueled vicious cycle.
AB  - Cancer cells exhibit unregulated growth, altered metabolism, enhanced metastatic
      potential and altered cell surface glycans. Fueled by oncometabolism and elevated
      uptake of glucose and glutamine, the hexosamine biosynthetic pathway (HBP)
      sustains glycosylation in the endomembrane system. In addition, the elevated
      pools of UDP-GlcNAc drives the O-GlcNAc modification of key targets in the
      cytoplasm, nucleus and mitochondrion. These targets include transcription
      factors, kinases, key cytoplasmic enzymes of intermediary metabolism, and
      electron transport chain complexes. O-GlcNAcylation can thereby alter
      epigenetics, transcription, signaling, proteostasis, and bioenergetics, key
      'hallmarks of cancer'. In this review, we summarize accumulating evidence that
      many cancer hallmarks are linked to dysregulation of O-GlcNAc cycling on cancer
      relevant targets. We argue that onconutrient and oncometabolite-fueled elevation
      increases HBP flux and triggers O-GlcNAcylation of key regulatory enzymes in
      glycolysis, Kreb's cycle, pentose-phosphate pathway, and the HBP itself. The
      resulting rerouting of glucose metabolites leads to elevated O-GlcNAcylation of
      oncogenes and tumor suppressors further escalating elevation in HBP flux creating
      a 'vicious cycle'. Downstream, elevated O-GlcNAcylation alters DNA repair and
      cellular stress pathways which influence oncogenesis. The elevated steady-state
      levels of O-GlcNAcylated targets found in many cancers may also provide these
      cells with a selective advantage for sustained growth, enhanced metastatic
      potential, and immune evasion in the tumor microenvironment.

PMID- 29594842
TI  - Associations between anxiolytic medications and ventral hernia repair.
AB  - PURPOSE: This study examines the relationship between anxiolytic medications
      (AXM) on outcomes following ventral hernia repair. METHODS: A single-center
      review of prospectively obtained perioperative and 30-day outcome data, including
      AXM use at admission, as part of the National Surgery Quality Improvement
      Program. RESULTS: Sixty-three of the 393 patients who presented for ventral
      hernia repair were taking an AXM (15.6%). AXM users were more likely to have a
      higher ASA class, dyspnea, and treated hypertension (p < 0.05). AXM use was
      associated with increased operative duration, hernia size, increased estimated
      blood loss, and need for component separation. After adjusting for medical
      comorbidities, AXM users were not found to have greater 30-day morbidity or
      mortality. Patients taking AXM were found to have greater length of stay and
      increased hospital readmissions. CONCLUSIONS: Patients taking anxiolytic
      medications undergoing ventral hernia repairs have higher ASA scores, more
      complex hernia characteristics, and require more concurrent procedures. They were
      found to have longer operative times, increased blood loss, greater duration of
      hospital stay, and increased readmissions that were associated with the increased
      perioperative risk factors. Further studies are required to determine causal
      links.

PMID- 29594843
TI  - Molecular cloning, expression, and functional characterization of the beta
      agarase AgaB-4 from Paenibacillus agarexedens.
AB  - In this study, a beta-agarase gene, agaB-4, was isolated for the first time from
      the agar-degrading bacterium Paenibacillus agarexedens BCRC 17346 by using next
      generation sequencing. agaB-4 consists of 2652 bp and encodes an 883-amino acid
      protein with an 18-amino acid signal peptide. agaB-4 without the signal peptide
      DNA was cloned and expressed in Escherichia coli BL21(DE3). His-tagged
      recombinant AgaB-4 (rAgaB-4) was purified from the soluble fraction of E. coli
      cell lysate through immobilized metal ion affinity chromatography. The optimal
      temperature and pH of rAgaB-4 were 55  degrees C and 6.0, respectively. The
      results of a substrate specificity test showed that rAgaB-4 could degrade agar,
      high-melting point agarose, and low-melting point agarose. The Vmax and Km of
      rAgaB-4 for low-melting point agarose were 183.45 U/mg and 3.60 mg/mL versus
      874.61 U/mg and 9.29 mg/mL for high-melting point agarose, respectively. The main
      products of agar and agarose hydrolysis by rAgaB-4 were confirmed to be
      neoagarotetraose. Purified rAgaB-4 can be used in the recovery of DNA from
      agarose gels and has potential application in agar degradation for the production
      of neoagarotetraose.

PMID- 29594844
TI  - Host-parasite association between Didelphis albiventris (Didelphimorphia:
      Didelphidae) and Ixodes loricatus (Acari: Ixodidae) in their southern ranges.
AB  - The parasitism of Ixodes loricatus Neumann on white-eared opposum, Didelphis
      albiventris Lund, was analysed in the southern ranges of both. In central
      Argentina, 118 wild opossums were captured from 2005 to 2012. Adults of I.
      loricatus were collected (prevalence = 66.1%, mean = 7.03, median = 4), but no
      immature stage. Tick infestation was not affected by sex (p = 0.27) or age (p =
      0.37) of hosts. In line with previous studies about seasonality of larvae and
      nymphs of I. loricatus, adult tick infestation showed no seasonal trend. This
      lack of seasonal pattern of infestation for all parasitic stages of I. loricatus
      may indicate a life cycle governed by nidicolous behaviour, in such a way that
      this habit would contribute to minimize the influence of external environmental
      variables. The tick sex ratio was female biased, with two females per one male (p
      = 0.002). The absence of I. loricatus immatures on D. albiventris suggests that
      in the study region there is clear segregation of immatures in rodents and adults
      in marsupials.

PMID- 29594845
TI  - Efficacy of carbon dioxide treatments for the control of the two-spotted spider
      mite, Tetranychus urticae, and treatment impact on plant seedlings.
AB  - To develop a new control method for the two-spotted spider mite (TSSM),
      Tetranychus urticae, we investigated the effect of controlled atmospheres of
      carbon dioxide (CO2) on TSSM mortality under different concentrations and
      treatment periods, and evaluated the impact of treatments on seedlings of five
      host plants of TSSM. Egg hatching rate of TSSM was reduced to 37.7, 5.4 or 0%
      after 24 h treatment involving concentrations of 16.7, 33.3 or 50%, respectively.
      Mobile stages (nymphs and adult) of TSSM were completely controlled after 24 h
      treatment at concentrations higher than 33.3%. After 4 h at concentrations of
      33.3 or 50%, 1st-day survival rate for all mobile stages was 45.3 or 36.0%,
      respectively, whereas after 8 or 16 h treatments, all values were decreased to
      zero. Seedlings of four major host plants of TSSM (cucumber, eggplant, rape,
      green peppers) were damaged to varying degrees after 24 h at the three
      concentrations, but strawberry, another host plant, was not damaged. Cucumber
      suffered the most serious damage, resulting in wilting and death. In conclusion,
      controlled atmospheres of CO2 can kill TSSM, particularly at high concentrations
      and with long treatment times. It can be used to control TSSM on strawberry, but
      should be used cautiously on other host plants.

PMID- 29594846
TI  - Prevalence and spatial distribution of Ixodid tick populations in the forest
      fringes of Western Ghats reported with human cases of Kyasanur forest disease and
      monkey deaths in South India.
AB  - Kyasanur forest disease (KFD) is a major tick-borne viral haemorrhagic fever
      caused by KFD virus (KFDV) (Flaviviridae). The disease was reported to be
      confined to five districts of Karnataka state India until 2011. During 2012-2016,
      emergence of KFD has been reported in newer areas of Karnataka and adjoining
      states. Therefore, survey of tick vectors was carried out in these new areas of
      Karnataka and adjoining states reported with monkey deaths and human cases of
      KFD. In all selected sites, ticks from the forest floor were collected by lint
      clothes using flagging method. Tick samples were tested for KFDV nucleic acid by
      real-time RT-PCR. A total of 4772 ticks, comprising eight species of genus
      Haemaphysalis and one species each of genus Amblyomma, Ixodes and Rhipicephalus
      was collected. Haemaphysalis spinigera, the principal vector of KFDV was the
      predominant tick species (59.5%) collected followed by H. turturis (8.6%). The
      abundance of H. spinigera ranged from 9.2 to 33.9 per man-hour in the six
      districts surveyed. Of 214 (4418 tick samples) pools screened by real-time RT
      PCR, two pools of H. spinigera were positive for KFDV. High abundance of
      Haemaphysalis vectors in the six districts indicated that the districts are
      receptive for KFD outbreaks. KFDV was detected in the tick vectors in the new
      foci of the KFD. Data on tick distribution will be useful in creating KFD risk
      map for strengthening the ongoing preventive measures such as vaccination and
      supply of insect repellents to the high risk groups and intensive health
      education.

PMID- 29594847
TI  - The combination of cardiorespiratory fitness and muscle strength, and mortality
      risk.
AB  - Little is known about the combined associations of cardiorespiratory fitness
      (CRF) and hand grip strength (GS) with mortality in general adult populations.
      The purpose of this study was to compare the relative risk of mortality for CRF,
      GS, and their combination. In UK Biobank, a prospective cohort of > 0.5 million
      adults aged 40-69 years, CRF was measured through submaximal bike tests; GS was
      measured using a hand-dynamometer. This analysis is based on data from 70,913 men
      and women (832 all-cause, 177 cardiovascular and 503 cancer deaths over 5.7-year
      follow-up) who provided valid CRF and GS data, and with no history of heart
      attack/stroke/cancer at baseline. Compared with the lowest CRF category, the
      hazard ratio (HR) for all-cause mortality was 0.76 [95% confidence interval (CI)
      0.64-0.89] and 0.65 (95% CI 0.55-0.78) for the middle and highest CRF categories,
      respectively, after adjustment for confounders and GS. The highest GS category
      had an HR of 0.79 (95% CI 0.66-0.95) for all-cause mortality compared with the
      lowest, after adjustment for confounders and CRF. Similar results were found for
      cardiovascular and cancer mortality. The HRs for the combination of highest CRF
      and GS were 0.53 (95% CI 0.39-0.72) for all-cause mortality and 0.31 (95% CI 0.14
      0.67) for cardiovascular mortality, compared with the reference category of
      lowest CRF and GS: no significant association for cancer mortality (HR 0.70; 95%
      CI 0.48-1.02). CRF and GS are both independent predictors of mortality. Improving
      both CRF and muscle strength, as opposed to either of the two alone, may be the
      most effective behavioral strategy to reduce all-cause and cardiovascular
      mortality risk.

PMID- 29594848
TI  - Hollow carbon dots labeled with FITC or TRITC for use in fluorescent cellular
      imaging.
AB  - Hollow carbon dots (HCDs) were prepared by a solvothermal method and conjugated
      to either tetramethyl rhodamine isothiocyanate (TRITC) or fluorescein-5
      isothiocyanate (FITC). This resulted in HCDs with bright red or green
      fluorescence, with excitation/emission peaks at 550/580 and 491/520 nm,
      respectively. The nanocomposites are well water-soluble, remarkably photostable
      and biocompatible. In addition, the fluorescence of the composites is more stable
      in a reactive oxygen environment than the free dyes. Confocal images indicate
      that the nanoparticles quickly enter A549 cells and mainly accumulate in the
      cytoplasm. The wavelength of functionalized HCDs can be regulating via coupling
      the HCDs to different dyes. These results demonstrate that these composite
      materials can be very promising reagents for biological labeling and imaging.
      Graphical abstract Schematic of the preparation of hollow carbon dots conjugated
      to tetramethyl rhodamine isothiocyanate (RHCDs) by solvothermal method. The
      material is water-soluble, remarkably photostable and biocompatible. It was
      applied to cellular labeling and imaging.

PMID- 29594849
TI  - Letter from the new Editor-in-Chief for Insights into Imaging.

PMID- 29594851
TI  - Endocavitary contrast enhanced ultrasound (CEUS): a novel problem solving
      technique.
AB  - : Contrast-enhanced ultrasound (CEUS) is a technique that has developed as an
      adjunct to conventional ultrasound. CEUS offers a number of benefits over
      conventional axial imaging with computerised tomography and magnetic resonance
      imaging, primarily as a "beside" test, without ionising radiation or the safety
      concerns associated with iodinated/gadolinium-based contrast agents.
      Intravascular use of ultrasound contrast agents (UCAs) is widespread with
      extensive evidence for effective use. Despite this, the potential utility of UCAs
      in physiological and non-physiological cavities has not been fully explored. The
      possibilities for endocavitary uses of CEUS are described in this review based on
      a single-centre experience including CEUS technique and utility in confirming
      drain placement, as well as within the biliary system, urinary system,
      gastrointestinal tract and intravascular catheters. TEACHING POINTS: * CEUS
      offers an excellent safety profile, spatial resolution and is radiation free. *
      Endocavitary CEUS provides real-time imaging similar to fluoroscopy in a portable
      setting. * Endocavitary CEUS can define internal architecture of physiological
      cavities. * Endocavitary CEUS can confirm drain position in physiological and non
      physiological cavities.

PMID- 29594852
TI  - Information architecture for a patient-specific dashboard in head and neck tumor
      boards.
AB  - PURPOSE: Overcoming the flaws of current data management conditions in head and
      neck oncology could enable integrated information systems specifically tailored
      to the needs of medical experts in a tumor board meeting. Clinical dashboards are
      a promising method to assist various aspects of the decision-making process in
      such cognitively demanding scenarios. However, in order to provide extensive and
      intuitive assistance to the participating physicians, the design and development
      of such a system have to be user-centric. To accomplish this task, conceptual
      methods need to be performed prior to the technical development and integration
      stages. METHODS: We have conducted a qualitative survey including eight clinical
      experts with different levels of expertise in the field of head and neck
      oncology. According to the principles of information architecture, the survey
      focused on the identification and causal interconnection of necessary metrics for
      information assessment in the tumor board. RESULTS: Based on the feedback by the
      clinical experts, we have constructed a detailed map of the required information
      items for a tumor board dashboard in head and neck oncology. Furthermore, we have
      identified three distinct groups of metrics (patient, disease and therapy
      metrics) as well as specific recommendations for their structural and graphical
      implementation. CONCLUSION: By using the information architecture, we were able
      to gather valuable feedback about the requirements and cognitive processes of the
      tumor board members. Those insights have helped us to develop a dashboard
      application that closely adapts to the specified needs and characteristics, and
      thus is primarily user-centric.

PMID- 29594850
TI  - Added value of double reading in diagnostic radiology,a systematic review.
AB  - OBJECTIVES: Double reading in diagnostic radiology can find discrepancies in the
      original report, but a systematic program of double reading is resource
      consuming. There are conflicting opinions on the value of double reading. The
      purpose of the current study was to perform a systematic review on the value of
      double reading. METHODS: A systematic review was performed to find studies
      calculating the rate of misses and overcalls with the aim of establishing the
      added value of double reading by human observers. RESULTS: The literature search
      resulted in 1610 hits. After abstract and full-text reading, 46 articles were
      selected for analysis. The rate of discrepancy varied from 0.4 to 22% depending
      on study setting. Double reading by a sub-specialist, in general, led to high
      rates of changed reports. CONCLUSIONS: The systematic review found rather low
      discrepancy rates. The benefit of double reading must be balanced by the
      considerable number of working hours a systematic double-reading scheme requires.
      A more profitable scheme might be to use systematic double reading for selected,
      high-risk examination types. A second conclusion is that there seems to be a
      value of sub-specialisation for increased report quality. A consequent
      implementation of this would have far-reaching organisational effects. KEY
      POINTS: * In double reading, two or more radiologists read the same images. * A
      systematic literature review was performed. * The discrepancy rates varied from
      0.4 to 22% in various studies. * Double reading by sub-specialists found high
      discrepancy rates.

PMID- 29594853
TI  - SUPRA: open-source software-defined ultrasound processing for real-time
      applications : A 2D and 3D pipeline from beamforming to B-mode.
AB  - PURPOSE: Research in ultrasound imaging is limited in reproducibility by two
      factors: First, many existing ultrasound pipelines are protected by intellectual
      property, rendering exchange of code difficult. Second, most pipelines are
      implemented in special hardware, resulting in limited flexibility of implemented
      processing steps on such platforms. METHODS: With SUPRA, we propose an open
      source pipeline for fully software-defined ultrasound processing for real-time
      applications to alleviate these problems. Covering all steps from beamforming to
      output of B-mode images, SUPRA can help improve the reproducibility of results
      and make modifications to the image acquisition mode accessible to the research
      community. We evaluate the pipeline qualitatively, quantitatively, and regarding
      its run time. RESULTS: The pipeline shows image quality comparable to a clinical
      system and backed by point spread function measurements a comparable resolution.
      Including all processing stages of a usual ultrasound pipeline, the run-time
      analysis shows that it can be executed in 2D and 3D on consumer GPUs in real
      time. CONCLUSIONS: Our software ultrasound pipeline opens up the research in
      image acquisition. Given access to ultrasound data from early stages (raw channel
      data, radiofrequency data), it simplifies the development in imaging.
      Furthermore, it tackles the reproducibility of research results, as code can be
      shared easily and even be executed without dedicated ultrasound hardware.

PMID- 29594854
TI  - Blended shared control utilizing online identification : Regulating grasping
      forces of a surrogate surgical grasper.
AB  - PURPOSE: Surgical robots are increasingly common, yet routine tasks such as
      tissue grasping remain potentially harmful with high occurrences of tissue crush
      injury due to the lack of force feedback from the grasper. This work aims to
      investigate whether a blended shared control framework which utilizes real-time
      identification of the object being grasped as part of the feedback may help
      address the prevalence of tissue crush injury in robotic surgeries. METHODS: This
      work tests the proposed shared control framework and tissue identification
      algorithm on a custom surrogate surgical robotic grasping setup. This scheme
      utilizes identification of the object being grasped as part of the feedback to
      regulate to a desired force. The blended shared control is arbitrated between
      human and an implicit force controller based on a computed confidence in the
      identification of the grasped object. The online identification is performed
      using least squares based on a nonlinear tissue model. Testing was performed on
      five silicone tissue surrogates. Twenty grasps were conducted, with half of the
      grasps performed under manual control and half of the grasps performed with the
      proposed blended shared control, to test the efficacy of the control scheme.
      RESULTS: The identification method resulted in an average of 95% accuracy across
      all time samples of all tissue grasps using a full leave-grasp-out cross
      validation. There was an average convergence time of [Formula: see text] ms
      across all training grasps for all tissue surrogates. Additionally, there was a
      reduction in peak forces induced during grasping for all tissue surrogates when
      applying blended shared control online. CONCLUSION: The blended shared control
      using online identification more successfully regulated grasping forces to the
      desired target force when compared with manual control. The preliminary work on
      this surrogate setup for surgical grasping merits further investigation on real
      surgical tools and with real human tissues.

PMID- 29594855
TI  - The Plasma Membrane Calcium Pump (PMCA): Regulation of Cytosolic Ca2+, Genetic
      Diversities and Its Role in Sub-plasma Membrane Microdomains.
AB  - In this chapter the four different genes of the mammalian plasma membrane calcium
      ATPase (PMCA) and their spliced isoforms are discussed with respect to the
      structural and functional properties of PMCA, the tissue distribution of the
      different isoforms, including their differences during development. The
      importance of PMCA for regulating Ca2+ signaling in microdomains under different
      conditions is also discussed.

PMID- 29594856
TI  - Structure-Function Relationship of the Voltage-Gated Calcium Channel Cav1.1
      Complex.
AB  - Voltage-gated calcium (Cav) channels are miniature membrane transistors that
      convert membrane electrical signals to intracellular Ca2+ transients that trigger
      many physiological events. In mammals, there are ten subtypes of Cav channel,
      among which Cav1.1 is the first Cavalpha1 to be cloned. Cav1.1 is specified for
      the excitation-contraction coupling of skeletal muscles, and has been a prototype
      in the structural investigations of Cav channels. This article summarized the
      recent advances in the structural elucidation of Cav1.1 and the mechanistic
      insights derived from the 3.6 A structure obtained using single-particle,
      electron cryomicroscopy. The structure of the Cav1.1 complex established the
      framework for mechanistic understanding of excitation-contraction coupling and
      provides the template for molecular interpretations of the functions and disease
      mechanisms of Cav and Nav channels.

PMID- 29594857
TI  - Structure-Dynamic Coupling Through Ca2+-Binding Regulatory Domains of Mammalian
      NCX Isoform/Splice Variants.
AB  - Mammalian Na+/Ca2+ exchangers (NCX1, NCX2, and NCX3) and their splice variants
      are expressed in a tissue-specific manner and are regulated by Ca2+ binding CBD1
      and CBD2 domains. NCX2 does not undergo splicing, whereas in NCX1 and NCX3, the
      splicing segment (with mutually exclusive and cassette exons) is located in CBD2.
      Ca2+ binding to CBD1 results in Ca2+-dependent tethering of CBDs through the
      network of interdomain salt-bridges, which is associated with NCX activation,
      whereas a slow dissociation of "occluded" Ca2+ inactivates NCX. Although NCX
      variants share a common structural basis for Ca2+-dependent tethering of CBDs,
      the Ca2+ off-rates of occluded Ca2+ vary up to 50-fold, depending on the exons
      assembly. The Ca2+-dependent tethering of CBDs rigidifies the interdomain
      movements of CBDs without any significant changes in the CBDs' alignment;
      consequently, more constraining conformational states become more populated in
      the absence of global conformational changes. Although this Ca2+-dependent
      "population shift" is a common mechanism among NCX variants, the strength and
      span of backbone rigidification from the C-terminal of CBD1 to the C-terminal of
      CBD2 is exon dependent. The mutually exclusive exons differentially
      stabilize/destabilize the backbone dynamics of Ca2+-bound CBDs in NCX1 and NCX3
      variants, whereas the cassette exons control the stability of the interdomain
      linker. The combined effects of mutually exclusive and cassette exons permit a
      fine adjustment of two different regulatory pathways: the Ca2+-dependent
      activation (controlled by CBD1) and the Ca2+-dependent alleviation of Na+-induced
      inactivation (controlled by CBD2). Exon-controlled dynamic features match with
      cell-specific regulatory requirements in a given variant.

PMID- 29594858
TI  - The Endoplasmic Reticulum and the Cellular Reticular Network.
AB  - The endoplasmic reticulum and the other organelles of the eukaryotic cell are
      membrane-bound structures that carry out specialized functions. In this chapter,
      we discuss strategies that the cell has adopted to link and coordinate the
      different activities occurring within its various organelles as the cell carries
      out its physiological role.

PMID- 29594859
TI  - Structure-Function Relationship of the SERCA Pump and Its Regulation by
      Phospholamban and Sarcolipin.
AB  - Calcium is a universal second messenger involved in diverse cellular processes,
      including excitation-contraction coupling in muscle. The contraction and
      relaxation of cardiac muscle cells are regulated by the cyclic movement of
      calcium primarily between the extracellular space, the cytoplasm and the
      sarcoplasmic reticulum (SR). The rapid removal of calcium from the cytosol is
      primarily facilitated by the sarco(endo)plasmic reticulum calcium ATPase (SERCA)
      which pumps calcium back into the SR lumen and thereby controls the amount of
      calcium in the SR. The most studied member of the P-type ATPase family, SERCA has
      multiple tissue- and cell-specific isoforms and is primarily regulated by two
      peptides in muscle, phospholamban and sarcolipin. The multifaceted regulation of
      SERCA via these peptides is exemplified in the biological fine-tuning of their
      independent oligomerization and regulation. In this chapter, we overview the
      structure-function relationship of SERCA and its peptide modulators, detailing
      the regulation of the complexes and summarizing their physiological and disease
      relevance.

PMID- 29594860
TI  - Structural Insights into IP3R Function.
AB  - Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed
      intracellular ligand-gated Ca2+ channels present on the endoplasmic reticulum of
      virtually all eukaryotic cells. These channels mediate the Ca2+ release from
      intracellular stores in response to activation by the signaling molecule IP3,
      which functions to transmit diverse signals received by the cell, e.g. from
      hormones, neurotransmitters, growth factors and hypertrophic stimuli, to various
      signaling pathways within the cell. Thus, IP3R channels can be conceptualized as
      highly dynamic scaffold membrane protein complexes, where binding of ligands can
      change the scaffold structure leading to cellular Ca2+ signals that direct
      markedly different cellular actions. Although extensively characterized in
      physiological and biochemical studies, the detailed mechanisms of how IP3Rs
      produce highly controlled Ca2+ signals in response to diversified extra- and
      intracellular stimuli remains unknown and requires high-resolution knowledge of
      channel molecular architecture. Recently, single-particle electron cryomicroscopy
      (cryo-EM) has yielded a long-awaited near-atomic resolution structure of the
      entire full-length type 1 IP3R. This structure provides important insights into
      the molecular underpinnings of ligand-mediated activation and regulation of IP3R.
      In this chapter, we evaluate available information and research progress on the
      structure of IP3R channel in an attempt to shed light on its function.

PMID- 29594861
TI  - IP3 Receptor Properties and Function at Membrane Contact Sites.
AB  - The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is a ubiquitously
      expressed Ca2+-release channel localized in the endoplasmic reticulum (ER). The
      intracellular Ca2+ signals originating from the activation of the IP3R regulate
      multiple cellular processes including the control of cell death versus cell
      survival via their action on apoptosis and autophagy. The exact role of the IP3Rs
      in these two processes does not only depend on their activity, which is modulated
      by the cytosolic composition (Ca2+, ATP, redox status, ...) and by various types
      of regulatory proteins, including kinases and phosphatases as well as by a number
      of oncogenes and tumor suppressors, but also on their intracellular localization,
      especially at the ER-mitochondrial and ER-lysosomal interfaces. At these
      interfaces, Ca2+ microdomains are formed, in which the Ca2+ concentration is
      finely regulated by the different ER, mitochondrial and lysosomal Ca2+-transport
      systems and also depends on the functional and structural interactions existing
      between them. In this review, we therefore discuss the most recent insights in
      the role of Ca2+ signaling in general, and of the IP3R in particular, in the
      control of basal mitochondrial bioenergetics, apoptosis, and autophagy at the
      level of inter-organellar contact sites.

PMID- 29594862
TI  - Structural Details of the Ryanodine Receptor Calcium Release Channel and Its
      Gating Mechanism.
AB  - Ryanodine receptors (RyRs) are large intracellular calcium release channels that
      play a crucial role in coupling excitation to contraction in both cardiac and
      skeletal muscle cells. In addition, they are expressed in other cell types where
      their function is less well understood. Hundreds of mutations in the different
      isoforms of RyR have been associated with inherited myopathies and cardiac
      arrhythmia disorders. The structure of these important drug targets remained
      elusive for a long time, despite decades of intensive research. In the recent
      years, a technical revolution in the field of single particle cryogenic electron
      microscopy (SP cryo-EM) allowed solving high-resolution structures of the
      skeletal and cardiac RyR isoforms. Together with the structures of individual
      domains solved by X-ray crystallography, this resulted in an unprecedented
      understanding of the structure, gating and regulation of these largest known ion
      channels. In this chapter we describe the recently solved high-resolution
      structures of RyRs, discuss molecular details of the channel gating, regulation
      and the disease mutations. Additionally, we highlight important questions that
      require further progress in structural studies of RyRs.

PMID- 29594863
TI  - Store-Operated Calcium Entry: An Historical Overview.
AB  - Store-operated calcium entry is a mechanism of Ca2+ signaling that has evolved
      from theory to molecules over a period of 30 years. This brief overview
      summarizes the major milestones that have led to the current concepts regarding
      the mechanisms and regulation of this most widely encountered of calcium
      signaling mechanisms.

PMID- 29594864
TI  - From Stores to Sinks: Structural Mechanisms of Cytosolic Calcium Regulation.
AB  - All eukaryotic cells have adapted the use of the calcium ion (Ca2+) as a
      universal signaling element through the evolution of a toolkit of Ca2+ sensor,
      buffer and effector proteins. Among these toolkit components, integral and
      peripheral proteins decorate biomembranes and coordinate the movement of Ca2+
      between compartments, sense these concentration changes and elicit physiological
      signals. These changes in compartmentalized Ca2+ levels are not mutually
      exclusive as signals propagate between compartments. For example, agonist induced
      surface receptor stimulation can lead to transient increases in cytosolic Ca2+
      sourced from endoplasmic reticulum (ER) stores; the decrease in ER luminal Ca2+
      can subsequently signal the opening surface channels which permit the movement of
      Ca2+ from the extracellular space to the cytosol. Remarkably, the minuscule
      compartments of mitochondria can function as significant cytosolic Ca2+ sinks by
      taking up Ca2+ in a coordinated manner. In non-excitable cells, inositol 1,4,5
      trisphosphate receptors (IP3Rs) on the ER respond to surface receptor
      stimulation; stromal interaction molecules (STIMs) sense the ER luminal Ca2+
      depletion and activate surface Orai1 channels; surface Orai1 channels selectively
      permit the movement of Ca2+ from the extracellular space to the cytosol; uptake
      of Ca2+ into the matrix through the mitochondrial Ca2+ uniporter (MCU) further
      shapes the cytosolic Ca2+ levels. Recent structural elucidations of these key
      Ca2+ toolkit components have improved our understanding of how they function to
      orchestrate precise cytosolic Ca2+ levels for specific physiological responses.
      This chapter reviews the atomic-resolution structures of IP3R, STIM1, Orai1 and
      MCU elucidated by X-ray crystallography, electron microscopy and NMR and
      discusses the mechanisms underlying their biological functions in their
      respective compartments within the cell.

PMID- 29594865
TI  - Assembly of ER-PM Junctions: A Critical Determinant in the Regulation of SOCE and
      TRPC1.
AB  - Store-operated calcium entry (SOCE), a unique plasma membrane Ca2+ entry
      mechanism, is activated when ER-[Ca2+] is decreased. SOCE is mediated via the
      primary channel, Orai1, as well as others such as TRPC1. STIM1 and STIM2 are ER
      Ca2+ sensor proteins that regulate Orai1 and TRPC1. SOCE requires assembly of
      STIM proteins with the plasma membrane channels which occurs within distinct
      regions in the cell that have been termed as endoplasmic reticulum (ER)-plasma
      membrane (PM) junctions. The PM and ER are in close proximity to each other
      within this region, which allows STIM1 in the ER to interact with and activate
      either Orai1 or TRPC1 in the plasma membrane. Activation and regulation of SOCE
      involves dynamic assembly of various components that are involved in mediating
      Ca2+ entry as well as those that determine the formation and stabilization of the
      junctions. These components include proteins in the cytosol, ER and PM, as well
      as lipids in the PM. Recent studies have also suggested that SOCE and its
      components are compartmentalized within ER-PM junctions and that this process
      might require remodeling of the plasma membrane lipids and reorganization of
      structural and scaffolding proteins. Such compartmentalization leads to the
      generation of spatially- and temporally-controlled Ca2+signals that are critical
      for regulating many downstream cellular functions.

PMID- 29594866
TI  - Beyond Intracellular Signaling: The Ins and Outs of Second Messengers
      Microdomains.
AB  - A typical characteristic of eukaryotic cells compared to prokaryotes is
      represented by the spatial heterogeneity of the different structural and
      functional components: for example, most of the genetic material is surrounded by
      a highly specific membrane structure (the nuclear membrane), continuous with, yet
      largely different from, the endoplasmic reticulum (ER); oxidative phosphorylation
      is carried out by organelles enclosed by a double membrane, the mitochondria; in
      addition, distinct domains, enriched in specific proteins, are present in the
      plasma membrane (PM) of most cells. Less obvious, but now generally accepted, is
      the notion that even the concentration of small molecules such as second
      messengers (Ca2+ and cAMP in particular) can be highly heterogeneous within
      cells. In the case of most organelles, the differences in the luminal levels of
      second messengers depend either on the existence on their membrane of proteins
      that allow the accumulation/release of the second messenger (e.g., in the case of
      Ca2+, pumps, exchangers or channels), or on the synthesis and degradation of the
      specific molecule within the lumen (the autonomous intramitochondrial cAMP
      system). It needs stressing that the existence of a surrounding membrane does not
      necessarily imply the existence of a gradient between the cytosol and the
      organelle lumen. For example, the nuclear membrane is highly permeable to both
      Ca2+ and cAMP (nuclear pores are permeable to solutes up to 50 kDa) and
      differences in [Ca2+] or [cAMP] between cytoplasm and nucleoplasm are not seen in
      steady state and only very transiently during cell activation. A similar
      situation has been observed, as far as Ca2+ is concerned, in peroxisomes.

PMID- 29594867
TI  - Mitochondrial VDAC, the Na+/Ca2+ Exchanger, and the Ca2+ Uniporter in Ca2+
      Dynamics and Signaling.
AB  - Mitochondrial Ca2+ uptake and release play pivotal roles in cellular physiology
      by regulating intracellular Ca2+ signaling, energy metabolism, and cell death.
      Ca2+ transport across the inner and outer mitochondrial membranes (IMM, OMM,
      respectively), is mediated by several proteins, including the voltage-dependent
      anion channel 1 (VDAC1) in the OMM, and the mitochondrial Ca2+ uniporter (MCU)
      and Na+-dependent mitochondrial Ca2+ efflux transporter, (the NCLX), both in the
      IMM. By transporting Ca2+ across the OMM to the mitochondrial inner-membrane
      space (IMS), VDAC1 allows Ca2+ access to the MCU, facilitating transport of Ca2+
      to the matrix, and also from the IMS to the cytosol. Intra-mitochondrial Ca2+
      controls energy production and metabolism by modulating critical enzymes in the
      tricarboxylic acid (TCA) cycle and fatty acid oxidation. Thus, by transporting
      Ca2+, VDAC1 plays a fundamental role in regulating mitochondrial Ca2+
      homeostasis, oxidative phosphorylation, and Ca2+ crosstalk among mitochondria,
      cytoplasm, and the endoplasmic reticulum (ER). VDAC1 has also been recognized as
      a key protein in mitochondria-mediated apoptosis, and apoptosis stimuli induce
      overexpression of the protein in a Ca2+-dependent manner. The overexpressed VDAC1
      undergoes oligomerization leading to the formation of a channel, through which
      apoptogenic agents can be released. Here, we review the roles of VDAC1 in
      mitochondrial Ca2+ homeostasis, in apoptosis, and in diseases associated with
      mitochondria dysfunction.

PMID- 29594868
TI  - Annexins: Ca2+ Effectors Determining Membrane Trafficking in the Late Endocytic
      Compartment.
AB  - Despite the discovery of annexins 40 years ago, we are just beginning to
      understand some of the functions of these still enigmatic proteins. Defined and
      characterized by their ability to bind anionic membrane lipids in a Ca2+
      dependent manner, each annexin has to be considered a multifunctional protein,
      with a multitude of cellular locations and diverse activities. Underlying causes
      for this considerable functional diversity include their capability to associate
      with multiple cytosolic and membrane proteins. In recent years, the increasingly
      recognized establishment of membrane contact sites between subcellular
      compartments opens a new scenario for annexins as instrumental players to link
      Ca2+ signalling with the integration of membrane trafficking in many facets of
      cell physiology. In this chapter, we review and discuss current knowledge on the
      contribution of annexins in the biogenesis and functioning of the late endocytic
      compartment, affecting endo- and exocytic pathways in a variety of physiological
      consequences ranging from membrane repair, lysosomal exocytosis, to cell
      migration.

PMID- 29594869
TI  - Ca2+ Signalling and Membrane Dynamics During Cytokinesis in Animal Cells.
AB  - Interest in the role of Ca2+ signalling as a possible regulator of the
      combinatorial processes that result in the separation of the daughter cells
      during cytokinesis, extend back almost a 100 years. One of the key processes
      required for the successful completion of cytokinesis in animal cells (especially
      in the large holoblastically and meroblastically dividing embryonic cells of a
      number of amphibian and fish species), is the dynamic remodelling of the plasma
      membrane. Ca2+ signalling was subsequently demonstrated to regulate various
      different aspects of cytokinesis in animal cells, and so here we focus
      specifically on the role of Ca2+ signalling in the remodelling of the plasma
      membrane. We begin by providing a brief history of the animal models used and the
      research accomplished by the early twentieth century investigators, with regards
      to this aspect of animal cell cytokinesis. We then review the most recent
      progress made (i.e., in the last 10 years), which has significantly advanced our
      current understanding on the role of cytokinetic Ca2+ signalling in membrane
      remodelling. To this end, we initially summarize what is currently known about
      the Ca2+ transients generated during animal cell cytokinesis, and then we
      describe the latest findings regarding the source of Ca2+ generating these
      transients. Finally, we review the current evidence about the possible targets of
      the different cytokinetic Ca2+ transients with a particular emphasis on those
      that either directly or indirectly affect plasma membrane dynamics. With regards
      to the latter, we discuss the possible role of the early Ca2+ signalling events
      in the deformation of the plasma membrane at the start of cytokinesis (i.e.,
      during furrow positioning), as well as the role of the subsequent Ca2+ signals in
      the trafficking and fusion of vesicles, which help to remodel the plasma membrane
      during the final stages of cell division. As it is becoming clear that each of
      the cytokinetic Ca2+ transients might have multiple, integrated targets,
      deciphering the precise role of each transient represents a significant (and
      ongoing) challenge.

PMID- 29594871
TI  - Solid-phase microextraction of sulfonylurea herbicides by using borate-reinforced
      multiple monolithic fibers.
AB  - Boron-nitrogen coordination is a useful interaction for use in the extraction of
      amino-nitrogen-containing compounds. A new monolithic adsorbent is described here
      that consisted of poly(acrylamidophenyl boronic acid/vinyl-3-octylimidazolium
      tetrafluroborate-co-divinylbenzene/ethylene dimethacrylate) polymer. It was
      synthesized with the aim to obtain a new kind of extraction phase for multiple
      monolith based fiber solid-phase microextraction of sulfonylurea herbicides.
      Results indicate that boron-nitrogen coordination interaction plays a key role in
      the efficient extraction. It is also found that soaking the sorbent in a borate
      solution further improves the enrichment performance. The preparation conditions
      and extraction parameters were optimized. Following extraction with the
      adsorbent, the sulfonylurea herbicides were submitted to quantitation by HPLC
      with DAD detection. The limits of detection are in the range of 9.0-18 ng.L-1.
      The method was applied to monitor the herbicides in samples of tap, river and
      waste waters. Recoveries at spiking levels of 1.0, 10 and 100 MUg.L-1 are in the
      range of 70.1-108%, and the values for relative standard deviation are less than
      10% for all analytes in all cases. Graphical abstract Schematic of the monolith
      based adsorbent (MBA) on a multiple monolith based fiber (MMF) for use in solid
      phase microextraction of sulfonylurea herbicides (SUs).

PMID- 29594870
TI  - Treatment Strategies for Dravet Syndrome.
AB  - Dravet syndrome (DS) is a medically refractory epilepsy that onsets in the first
      year of life with prolonged seizures, often triggered by fever. Over time,
      patients develop other seizure types (myoclonic, atypical absences, drops),
      intellectual disability, crouch gait and other co-morbidities (sleep problems,
      autonomic dysfunction). Complete seizure control is generally not achievable with
      current therapies, and the goals of treatment are to balance reduction of seizure
      burden with adverse effects of therapies. Treatment of co-morbidities must also
      be addressed, as they have a significant impact on the quality of life of
      patients with DS. Seizures are typically worsened with sodium-channel agents.
      Accepted first-line agents include clobazam and valproic acid, although these
      rarely provide adequate seizure control. Benefit has also been noted with
      topiramate, levetiracetam, the ketogenic diet and vagal nerve stimulation.
      Several agents presently in development, specifically fenfluramine and
      cannabidiol, have shown efficacy in clinical trials. Status epilepticus is a
      recurring problem for patients with DS, particularly in their early childhood
      years. All patients should be prescribed a home rescue therapy (usually a
      benzodiazepine) but should also have a written seizure action plan that outlines
      when rescue should be given and further steps to take in the local hospital if
      the seizure persists despite home rescue therapy.

PMID- 29594873
TI  - Reliability and validity of the Short Falls Efficacy Scale-International for
      Japanese older people.
AB  - BACKGROUND: The Short Falls Efficacy Scale-International (Short FES-I) has been
      confirmed to be a good measure with reliability and validity in a UK sample;
      however, the reliability and validity of the Short FES-I for Japanese older
      people have not yet been established. AIM: The aim of this study was to determine
      the reliability and validity of the Short FES-I for Japanese older people.
      METHODS: The study participants were 519 older people aged 65 years and over who
      were living independently in their community. The Short FES-I is composed of
      seven items rated on a four-point Likert scale. Lower scores indicate better fall
      related efficacy. To investigate the validity of the Short FES-I, previous falls,
      physical function such as grip strength and scores on the Timed Up and Go (TUG)
      test, psychological factors such as self-rated health (SRH), cognitive function,
      and other confounding factors were collected. The association between the
      previous falls and the Short FES-I was analyzed using logistic regression
      analysis. Furthermore, factors related to the Short FES-I were investigated using
      multiple regression analysis. RESULTS: Cronbach's alpha for the Short FES-I was
      0.87. Short FES-I scores were significantly higher in participants with a history
      of falls than in those without. In addition, Short FES-I scores were
      significantly and independently associated with falls in logistic regression
      analysis, and significantly associated with grip strength, TUG time, and SRH in
      multiple regression analysis. CONCLUSIONS AND DISCUSSION: These results suggest
      that the Short FES-I is a reliable and valid fall-related measurement scale for
      Japanese older people.

PMID- 29594872
TI  - Calcium/calmodulin-stimulated adenylyl cyclases 1 and 8 regulate reward-related
      brain activity and ethanol consumption.
AB  - Evidence suggests a predictive link between elevated basal activity within reward
      related networks (e.g., cortico-basal ganglia-thalamic networks) and
      vulnerability for alcoholism. Both calcium channel function and cyclic adenosine
      monophosphate (cAMP)/protein kinase A-mediated signaling are critical modulators
      of reward neurocircuitry and reward-related behaviors. Calcium/calmodulin
      stimulated adenylyl cyclases (AC) 1 and 8 are sensitive to activity-dependent
      increases in intracellular calcium and catalyze cAMP production. Therefore, we
      hypothesized AC1 and 8 regulate brain activity in reward regions of the cortico
      basal ganglia-thalamic circuit and that this regulatory influence predicts
      voluntary ethanol drinking responses. This hypothesis was evaluated by manganese
      enhanced magnetic resonance imaging and chronic, intermittent ethanol access
      procedures. Ethanol-naive mice with genetic deletion of both AC1 and 8 (DKO mice)
      exhibited bilateral reductions in baseline activity within cortico-basal ganglia
      thalamic regions associated with reward processing compared to wild-type controls
      (WT, C57BL/6 mice). Significant activity changes were not evident in regions
      either outside of the cortico-basal ganglia-thalamic network or within the
      network that are not associated with reward processing. Parallel studies
      demonstrated that reward network hypoactivity in DKO mice predicted a significant
      attenuation in consumption and preference levels to escalating ethanol
      concentrations (12, 20 and 30%) compared to WT mice, an effect that was
      maintained over extended access (14 sessions) to 20% ethanol. Summarizing, these
      data support a contribution of AC1 and 8 in cortico-basal ganglia-thalamic
      activity and the predictive value of this regulatory influence on ethanol
      drinking behavior, which merits the future evaluation of calcium-stimulated ACs
      in the neural processes that engender vulnerability to maladaptive alcohol
      drinking.

PMID- 29594874
TI  - Oligometastatic cancer in elderly patients: the "blitzkrieg" radiotherapy
      approach
AB  - AIMS: To retrospectively evaluate the outcome of stereotactic body radiation
      therapy (SBRT) in the treatment of elderly patients affected by isolated body
      metastasis from different primitive tumors. METHODS: 70 patients with isolated
      body metastasis were treated. Median age at diagnosis was 75 years (IQR 69-80).
      The most common SBRT fractionation scheme was 5 * 7 Gy (total dose 35 Gy). The
      primary endpoints were Local Control (LC) and Toxicity. Secondary endpoints were
      Overall Survival (OS) and Disease-Specific Survival (DSS). Response to
      radiotherapy was assessed according to RECIST criteria v1.1. Toxicity was
      registered according to Common Terminology Criteria for Adverse Events (CTCAE) v
      4.0. We performed survival analysis with the Kaplan-Meier method. The correlation
      between time actuarial incidence and clinical parameters was studied. RESULTS:
      Median follow-up was 26.5 months. 44 patients (62.8%) were alive at the time of
      analysis, while 22 (31.4%) died because of the disease. Local control at 2 and 3
      years was 87%. The 2-year OS and DSS were 84 and 71%, respectively, while the 3
      year values were 57 and 62%. PFS at 2 and 3 years was 41 and 25%, respectively.
      On univariate analysis, KPS >= 90 is statistically correlated with improved OS
      and DSS (p < 0.05). Acute toxicity of grade >= 2 occurred in 4 (5.7%) patients,
      while late toxicity >= 2 was recorded in 6 (8.6%) patients. CONCLUSIONS: Ablative
      Radiotherapy represents a safe, effective, and minimally invasive treatment
      modality for elderly oligometastatic patients who are judged unfit for systemic
      therapy.

PMID- 29594875
TI  - Comprehensive review of the epidemiology and treatments for malignant adult
      cardiac tumors.
AB  - Carcinomas rarely occur in the heart, and cardiac surgeons are generally not
      familiar with cardiac tumors. Some characteristics of cardiac and
      intrapericardial tumors are reviewed to understand the features of cardiac
      tumors. Cardiac tumors are discussed separately from intrapericardial tumors.
      Primary cardiac tumors are predominantly benign whereas primary intrapericardial
      tumors are usually malignant. The prevalence of each tumor types is presented in
      this review. In both cardiac and intrapericardial tumors, the incidences of
      metastatic tumors from cancers outside of the heart are high with carcinomas
      occupying more than half of the cases. Generally, the prognosis of primary
      malignant cardiac tumors is very poor. Cardiac tumors metastasize to other organs
      as hematogenous metastases. Surgery must be performed based on all the above
      mentioned features of both cardiac and intrapericardial tumors.

PMID- 29594876
TI  - Is the frozen elephant trunk frozen?
AB  - The elephant trunks, either conventional or frozen represent the major technical
      improvements in the treatment of complex thoracic aortic disease. In the last
      decades, these useful techniques progressively evolved along with the
      introduction of new devices to facilitate the procedure and ameliorate post
      operative results. The latest multi-branched hybrid FET prostheses give us the
      opportunity to greatly facilitate graft implantation and reduce operative times.
      The following review will provide an overview of the FET technique throughout the
      current available devices, possible surgical indications and principal surgical
      steps.

PMID- 29594877
TI  - Granulocyte colony stimulating factor-producing lung cancer with severe anemia of
      inflammation.
AB  - Granulocyte colony stimulating factor (G-CSF)-producing lung cancer occasionally
      induces severe inflammation with an abnormally high white blood cell count.
      Herein, we report a 49-year-old man who suffered from resectable G-CSF-producing
      non-small cell lung cancer with continuous fever and severe anemia. Red blood
      cell transfusion was necessary for the anemia of inflammation. The patient
      underwent complete surgical tumor resection. The histopathological diagnosis was
      a pleomorphic carcinoma at pathological stage IIB. This is apparently the first
      successful case of surgical resection of G-CSF-producing lung cancer in a patient
      with severe anemia and uncontrollable fever.

PMID- 29594878
TI  - Acquired resistance to an epidermal growth factor receptor-tyrosine kinase
      inhibitor (EGFR-TKI) in an uncommon G719S EGFR mutation.
AB  - Background Acquired resistance (AR) to an epidermal growth factor receptor
      tyrosine kinase inhibitor (EGFR-TKI) is a common event, and several underlying
      mechanisms, including T790 M, MET amplification and PTEN downregulation, have
      been reported for the common EGFR mutations. EGFR G719X is an uncommon mutation
      that has been reported to show sensitivity to EGFR-TKIs. However, no established
      cell lines harboring the EGFR G719X have been reported in the literature.
      Materials and Methods G719S-GR cells were established from malignant pleural
      effusion of a patient whose tumor developed AR from gefitinib treatment. G719S-GR
      cells were then genotyped and tested for drug sensitivities. Multiplex ligation
      dependent probe amplification (MLPA) was used to compare the clinical tumor
      samples with G719S-GR. Results G719S-GR cells were resistant to EGFR-TKIs with an
      LC50 of around 10 MUM. A genomic analysis showed that G719S-GR cells harbor the
      EGFR G719S mutation as well as the amplification of EGFR locus. The homozygous
      deletion of CDKN2A and the loss of PTEN and TSC1 were also detected. On comparing
      the copy number of tumor suppressor genes using MLPA, G719S-GR cells were found
      to lack one copy of PTEN, which was not observed in a tumor obtained before
      gefitinib treatment. Loss of PTEN may result in AKT activation. The mTORC1/2
      inhibitor Torin-1 was able to inhibit the downstream signaling when combined with
      osimertinib. Discussion The newly established G719S-GR cell line may be useful
      for investigating the mechanism underlying the development of AR in the G719X
      mutation; the loss of PTEN may be one such mechanism.

PMID- 29594879
TI  - Matrix-MTM adjuvant enhances immunogenicity of both protein- and modified
      vaccinia virus Ankara-based influenza vaccines in mice.
AB  - Influenza viruses continuously circulate in the human population and escape
      recognition by virus neutralizing antibodies induced by prior infection or
      vaccination through accumulation of mutations in the surface proteins
      hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a
      vaccine that provides broad protection against different influenza A viruses are
      under investigation, including use of recombinant (r) viral vectors and
      adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a
      promising vaccine vector that efficiently induces B and T cell responses specific
      for the antigen of interest. It is assumed that live vaccine vectors do not
      require an adjuvant to be immunogenic as the vector already mediates recruitment
      and activation of immune cells. To address this topic, BALB/c mice were
      vaccinated with either protein- or rMVA-based HA influenza vaccines, formulated
      with or without the saponin-based Matrix-MTM adjuvant. Co-formulation with Matrix
      M significantly increased HA vaccine immunogenicity, resulting in antigen
      specific humoral and cellular immune responses comparable to those induced by
      unadjuvanted rMVA-HA. Of special interest, rMVA-HA immunogenicity was also
      enhanced by addition of Matrix-M, demonstrated by enhanced HA inhibition antibody
      titres and cellular immune responses. Matrix-M added to either protein- or rMVA
      based HA vaccines mediated recruitment and activation of antigen-presenting cells
      and lymphocytes to the draining lymph node 24 and 48 h post-vaccination. Taken
      together, these results suggest that adjuvants can be used not only with protein
      based vaccines but also in combination with rMVA to increase vaccine
      immunogenicity, which may be a step forward to generate new and more effective
      influenza vaccines.

PMID- 29594880
TI  - Toxicity evaluation of process water from hydrothermal carbonization of sugarcane
      industry by-products.
AB  - Hydrothermal carbonization (HTC) is a thermochemical process carried out in an
      aqueous medium. It is capable of converting biomass into a solid, carbon-rich
      material (hydrochar), and producing a liquid phase (process water) which contains
      the unreactive feedstock and/or chemical intermediates from the carbonization
      reaction. The aim of this study was to evaluate the characteristics of process
      water generated by HTC from vinasse and sugarcane bagasse produced by sugarcane
      industry and to evaluate its toxicity to both marine (using Artemia salina as a
      model organism) and the terrestrial environment (through seed germination studies
      of maize, lettuce, and tomato). The experiments showed that concentrated process
      water completely inhibited germination of maize, lettuce, and tomato seeds. On
      the other hand, diluted process water was able to stimulate seedlings of maize
      and tomato and enhance root and shoot growth. For Artemia, the LC50 indicated
      that the process water is practically non-toxic; however, morphological changes,
      especially damages to the digestive tube and antennas of Artemia, were observed
      for the concentration of 1000 mg C L-1.

PMID- 29594881
TI  - Potential application of pre-treated municipal solid waste incineration fly ash
      as cement supplement.
AB  - Pre-treatment process carried out on raw municipal solid waste incineration
      (MSWI) fly ash (FA) sample that did not comply initially with the USEPA method
      1311 toxicity characteristic leaching procedure (TCLP) regulatory limits of 2011
      reduced its chloride and heavy metal content appreciably, thereby making it
      compliant with the aforementioned regulatory requirement. More than 98% of each
      heavy metal was successfully removed. The process was excellent in removing
      cadmium (Cd) (99.99%) and very good at removing the rest. About 99.96% of Cu was
      eliminated, 99.96% of cobalt (Co), 99.95% of Zn, 98.61% of Cr, and 98.12% of
      nickel (Ni). Also, the leachate resulting from these pre-treatment steps met the
      China (GB 16889-2008) and USEPA method 1311 regulatory standards for safe
      discharge. The density and compressive strength of all the samples prepared
      increased as the FA content decreased. The compressive strength of all the
      samples passed the 1989 USEPA-recommended value of 0.34 MPa (50 psi), thereby
      making them suitable for industrial application. The sample that attained the
      highest compressive strength (2.08 MPa) after 28 days of curing incorporated 55%
      fly ash (FACS55), while the one with the least compressive strength (0.65 MPa)
      after the same period was made from only fly ash (FACS100). Moreover, the
      concentration of heavy metals in all the samples generally decreased with the FA
      content. Chromium was not detected in all the samples, thereby making this an
      excellent method for its immobilization. From the leachability test results, all
      the samples prepared met the USEPA method 1311 TCLP regulatory limits.

PMID- 29594882
TI  - Decomposition dynamic of two aquatic macrophytes Trapa bispinosa Roxb. and
      Nelumbo nucifera detritus.
AB  - In freshwater ecosystems, aquatic macrophytes play significant roles in nutrient
      cycling. One problem in this process is nutrient loss in the tissues of untimely
      harvested plants. In this study, we used two aquatic species, Nelumbo nucifera
      and Trapa bispinosa Roxb., to investigate the decomposition dynamics and nutrient
      release from detritus. Litter bags containing 10 g of stems (plus petioles) and
      leaves for each species detritus were incubated in the pond from November 2016 to
      May 2017. Nine times litterbags were retrieved on days 6, 14, 25, 45, 65, 90,
      125, 145, and 165 after the decomposition experiment for the monitoring of
      biomass loss and nutrient release. The results suggested that the dry masses of
      N. nucifera and T. bispinosa decomposed by 49.35-69.40 and 82.65-91.65%,
      respectively. The order of decomposition rate constants (k) is as follows: leaves
      of T. bispinosa (0.0122 day-1) > stems (plus petioles) of T. bispinosa (0.0090
      day-1) > leaves of N. nucifera (0.0060 day-1) > stems (plus petioles) of N.
      nucifera (0.0030 day-1). Additionally, the orders of time for 50% dry mass decay,
      time for 95% dry mass decay, and turnover rate are as follows: leaves < stems
      (plus petioles) and T. bispinosa < N. nucifera, respectively. This result
      indicated that the dry mass loss, k values, and other parameters related to k
      values are significantly different in species- and tissue-specific. The C, N, and
      P concentration and the C/N, C/P, and N/P ratios presented the irregular temporal
      changes trends during the whole decay period. In addition, nutrient accumulation
      index (AI) was significantly changed depending on the dry mass remaining and C,
      N, and P concentration in detritus at different decomposition times. The nutrient
      AIs were 36.72, 8.08, 6.35, and 2.56% for N; 31.25, 9.85, 4.00, and 1.63% for P;
      25.15, 16.96, 7.36, and 6.16% for C in the stems (plus petioles) of N. nucifera,
      leaves of N. nucifera, stems (plus petioles) of T. bispinosa, and leaves of T.
      bispinosa, respectively, at the day 165. These results indicated that 63.28
      97.44% of N, 68.75-98.37% of P, and 74.85-93.84% of C were released from the
      plant detritus to the water at the day 165 of the decomposition period. The
      initial detritus chemistry, particularly the P-related parameters (P
      concentration and C/P and N/P ratios), strongly affected dry mass loss,
      decomposition rates, and nutrient released from detritus into water. Two-way
      ANOVA results also confirm that the effects on the species were significant for
      decomposition dynamics (dry mass loss), nutrient release (nutrient concentration,
      their ratios, and nutrient AI) (P < 0.01), and expected N concentration (P >
      0.05). In addition, the decomposition time had also significant effects on the
      detritus decomposition dynamic and nutrient release. However, the contributors of
      species and decomposition time on detritus decomposition were significantly
      different on the basis of their F values of two-way ANOVA results. This study can
      provide scientific bases for the aquatic plant scientific management in
      freshwater ecosystems of the East region of China.

PMID- 29594883
TI  - Effect of hydration status on pesticide uptake in anurans following exposure to
      contaminated soils.
AB  - In this study, the impact of hydration status on dermal uptake of pesticides in
      two species of amphibians is examined. Absorption of pesticides in anurans occurs
      primarily through a highly vascularized dermal seat patch; however, pesticides
      can also enter through the superficial dermis following exposure. Despite the
      growing body of literature on dermal exposure in amphibians, little is known on
      how hydration status influences uptake. Thus, the objective of this study was to
      investigate the influence of hydration status on absorption of pesticides
      (atrazine, triadimefon, metolachlor, chlorothalonil, and imidacloprid) in
      southern leopard frogs (Lithobates sphenocephala) and Fowler's toads (Anaxyrus
      fowleri). Amphibian treatments included dehydration periods of 0, 2, 4, 6, 8, or
      10 h prior to exposure to pesticide-contaminated soils for 8 h. Following
      exposure, soil and whole-body homogenates were extracted and analyzed by LC
      MS/MS. Dehydration time was then regressed against post-exposure concentrations
      to infer the impact of dehydration on dermal pesticide uptake. Increased
      dehydration time resulted in significantly lowered pesticide concentrations in
      both species (F6, 293 = 67.66, p = 0.007) for the five pesticides studied. This
      phenomenon could be due to an energy and/or dilution effect.

PMID- 29594884
TI  - An eco-friendly method for heavy metal removal from mine tailings.
AB  - One of the serious environmental problems that society is facing today is mine
      tailings. These byproducts of the process of extraction of valuable elements from
      ores are a source of pollution and a threat to the environment. For example, mine
      tailings from past mining activities at Giant Mines, Yellowknife, are deposited
      in chambers, stopes, and tailing ponds close to the shores of The Great Slave
      Lake. One of the environmentally friendly approaches for removing heavy metals
      from these contaminated tailing is by using biosurfactants during the process of
      soil washing. The objective of this present study is to investigate the effect of
      sophorolipid (SL) concentration, the volume of washing solution per gram of
      medium, pH, and temperature on the efficiency of sophorolipids in removing heavy
      metals from mine tailings. It was found that the efficiency of the sophorolipids
      depends on its concentration, and is greatly affected by changes in pH, and
      temperature. The results of this experiment show that increasing the temperature
      from 15 to 23  degrees C, while using sophorolipids, resulted in an increase in
      the removal of iron, copper, and arsenic from the mine tailing specimen, from
      0.25, 2.1, and 8.6 to 0.4, 3.3, and 11.7%. At the same time, increasing the
      temperature of deionized water (DIW) from 15 to 23  degrees C led to an increase
      in the removal of iron, copper, and arsenic from 0.03, 0.9, and 1.8 to 0.04, 1.1,
      and 2.1%, respectively. By increasing temperature from 23 to 35  degrees C, when
      using sophorolipids, 22% reduction in the removal of arsenic was observed. At the
      same time while using DI water as the washing solution, increasing temperature
      from 23 to 35  degrees C resulted in 6.2% increase in arsenic removal. The
      results from this present study indicate that sophorolipids are promising agents
      for replacing synthetic surfactants in the removal of arsenic and other heavy
      metals from soil and mine tailings.

PMID- 29594885
TI  - Effect on human health of the arsenic pollution and hydrogeochemistry of the
      Yazir Lake wetland (Cavdir-Burdur/Turkey).
AB  - In this study, the physicochemical parameters, major ions and arsenic (As)
      contents of water resources in the Yazir lake wetland, were evaluated. In
      addition, water resources in this region were investigated from the point of
      water quality and health risk assessment. Thirty water samples were collected
      from the area in dry and wet seasons. Ca-Mg-HCO3 and Ca-HCO3 were the dominant
      water types. The Gibbs diagram suggests that most of the samples fall in rock
      dominance zone, which indicates the groundwater interaction between rock
      chemistry. When compared to drinking water guidelines established by World Health
      Organization and Turkey, much greater attention should be paid to As, Fe, and Mn
      through varied chemicals above the critical values. According to the pH-ORP
      diagram, the predominant species is arsenate (H2AsO4-2). The high concentrations
      of As in the surface water and groundwater are related to oxidative and reductive
      dissolution reaction of Fe and Mn hydroxides within the Kizilcadag ophiolite and
      melange. In addition, the seasonal changes in As concentrations depend on the
      increase in pH of water samples. The major toxic and carcinogenic chemical within
      water samples is As for groundwater and surface water. From the results of hazard
      index, it is verified that As which is taken by ingestion of water was the main
      contaminant, and toxic human risk in the study area. The obtained results will
      help define strategies for As problems in the water resources in future.

PMID- 29594886
TI  - Explaining the accelerated degradation of ciprofloxacin, sulfamethazine, and
      erythromycin in different soil exposure scenarios by their aqueous
      extractability.
AB  - Antibiotics are frequently introduced into agricultural soils with the
      application of sewage sludge or farm organic fertilizers. Repeated exposure of
      soils to a pollutant can enrich for microbial populations that metabolize the
      chemical, reducing its environmental persistence. In London, Canada, soils from a
      long-term field experiment have received different concentrations of antibiotics
      annually for several years. The purpose of the present study was to assess the
      bioavailability of sulfamethazine, erythromycin, or ciprofloxacin through aqueous
      extractions with borax or EDTA solutions and their biodegradation following
      different soil exposure scenarios. Control soils and soils treated annually in
      the field with 10 mg antibiotics per kg were sampled, supplemented in the
      laboratory with radiolabeled antibiotic either added directly or carried in dairy
      manure. Sulfamethazine and erythromycin were initially more bioavailable than
      ciprofloxacin, with aqueous extractabilities representing 60, 36, and 8%,
      respectively. Sulfamethazine and erythromycin were degraded in soils, with a
      larger fraction mineralized in the long-term exposed soil (20 and 65%,
      respectively) than in control soil (0.4 and 3%, respectively) after 7 days of
      incubation. In contrast, ciprofloxacin was not mineralized neither in control nor
      long-term exposed soils. The mineralized fractions were similar for antibiotics
      added directly to soil or carried in dairy manure.

PMID- 29594887
TI  - Purifying arsenic and fluoride-contaminated water by a novel graphene-based
      nanocomposite membrane of enhanced selectivity and sustained flux.
AB  - A novel graphene-based nanocomposite membrane was synthesized by interfacial
      polymerization (IP) through chemical bonding of the graphene oxide (GO) layer to
      polyethersulfone surface. Detailed characterization of the composite membrane
      through AFM, SEM, ATR-FTIR, XRD analysis, and Raman spectroscopy indicates strong
      potential of the membrane in highly selective removal of the toxic contaminants
      like arsenic and fluoride while permeating the essential minerals like calcium
      and magnesium. This makes the membrane suitable for production of safe drinking
      water from contaminated water. The membrane applied in a flat-sheet cross-flow
      module succeeded in removal of more than 98% arsenic and around 80% fluoride from
      contaminated water while selectively retaining the useful calcium and magnesium
      minerals in drinking water. A sustained pure water flux of around 150 LMH (liter
      per square meter per hour) during operation over long hours (> 150 h) with only 3
      5% drop in flux indicates antifouling character of the membrane module.

PMID- 29594888
TI  - An analysis of the dust deposition on solar photovoltaic modules.
AB  - Solid particles impair the performance of the photovoltaic (PV) modules. This
      results in power losses which lower the efficiency of the system as well as the
      increases of temperature which additionally decreases the performance and
      lifetime. The deposited dust chemical composition, concentration and formation of
      a dust layer on the PV surface differ significantly in reference to time and
      location. In this study, an evaluation of dust deposition on the PV front cover
      glass during the non-heating season in one of the most polluted European cities,
      Krakow, was performed. The time-dependent particle deposition and its correlation
      to the air pollution with particulate matter were analysed. Dust deposited on
      several identical PV modules during variable exposure periods (from 1 day up to 1
      week) and the samples of total suspended particles (TSP) on quartz fibre filters
      using a low volume sampler were collected during the non-heating season in the
      period of 5 weeks. The concentration of TSP in the study period ranged between
      12.5 and 60.05 MUg m-3 while the concentration of PM10 observed in the
      Voivodeship Inspectorate of Environmental Protection traffic station, located 1.2
      km from the TSP sampler, ranged from 14 to 47 MUg m-3. It was revealed that dust
      deposition density on a PV surface ranged from 7.5 to 42.1 mg m-2 for exposure
      periods of 1 day while the measured weekly dust deposition densities ranged from
      25.8 to 277.0 mg m-2. The precipitation volume and its intensity as well as
      humidity significantly influence the deposited dust. The rate of dust
      accumulation reaches approximately 40 mg m-2day-1 in the no-precipitation period
      and it was at least two times higher than fluxes calculated on the basis of PM10
      and TSP concentrations which suggest that additional forces such as electrostatic
      forces significantly influence dust deposition.

PMID- 29594889
TI  - Lost in 'Culturation': medical informed consent in China (from a Western
      perspective).
AB  - Although Chinese law imposes informed consent for medical treatments, the Chinese
      understanding of this requirement is very different from the European one, mostly
      due to the influence of Confucianism. Chinese doctors and relatives are primarily
      interested in protecting the patient, even from the truth; thus, patients are
      commonly uninformed of their medical conditions, often at the family's request.
      The family plays an important role in health care decisions, even substituting
      their decisions for the patient's. Accordingly, instead of personal informed
      consent, what actually exists is 'family informed consent'. From a Western
      perspective, these features of Chinese law and Chinese culture might seem
      strange, contradicting our understanding of doctor-patient relationship and even
      the very essence of self-determination and fundamental rights. However, we cannot
      forget the huge influence of cultural factors in these domains, and that
      'Western' informed consent is grounded on the individualistic nature of Western
      culture. This article will underline the differences between the Western and the
      Chinese perspectives, clarifying how each of them must be understood in its own
      cultural environment. But, while still respecting Chinese particularities, this
      paper advocates that China adopt patient individual informed consent because this
      is the only solution compatible with human dignity and human rights.

PMID- 29594890
TI  - Comparative evaluation of fermented and non-fermented de-oiled rice bran with or
      without exogenous enzymes supplementation in the diet of Labeo rohita (Hamilton,
      1822).
AB  - A 60-day feeding trial was conducted to study the effect of exogenous enzymes
      (xylanase and phytase) supplementation in the non-fermented and fermented de
      oiled rice bran (DORB)-based diet of Labeo rohita. Four test diets (T1-DORB-based
      diet, T2-fermented DORB-based diet, T3-phytase and xylanase supplemented DORB
      based diet, and T4-phytase and xylanase supplemented fermented DORB-based diet)
      were formulated and fed to the respective groups. Test diets T3 and T4 were
      supplemented with 0.01% xylanase (16,000 U kg-1) and 0.01% phytase (500 U kg-1)
      enzymes. One hundred twenty juveniles of L. rohita, with an average weight 5.01
      +/- 0.02 g, were stocked in 12 uniform size plastic rectangular tanks in
      triplicate with 10 fishes per tank following a completely randomized design
      (CRD). Exogenous enzyme supplementation to the T3 group significantly improved
      the growth performance of L. rohita (p < 0.05). Fermented DORB fed groups
      registered significantly lower growth irrespective of the supplementation of
      exogenous enzymes. The carcass composition (except CP %), enzyme activities
      (except amylase activity), globulin, and A/G ratio did not vary significantly (p
      > 0.05). Based on the results of the present study, it is concluded that
      exogenous enzyme supplementation significantly increases the growth of fish fed
      with DORB-based diet.

PMID- 29594891
TI  - Removal of totally implanted venous access ports for suspected infection in the
      intensive care unit: a multicenter observational study.
AB  - BACKGROUND: While no data support this practice, international guidelines
      recommend the removal of totally implanted venous access ports (TIVAPs) in
      patients with suspicion of TIVAP-related bloodstream infection admitted in the
      intensive care unit (ICU) for a life-threatening sepsis. METHODS: During this
      multicenter, retrospective and observational study, we included all patients
      admitted in five ICU for a life-threatening sepsis in whom a TIVAP was removed
      between January 2012 and December 2014. We aimed (1) at determining the
      proportion of confirmed TIVAP-related infections and (2) at assessing short- and
      long-term survival of patients with and without TIVAP-related infections.
      RESULTS: One hundred and fifty-one patients (58 +/- 14 years, 62% males) were
      included between 2012 and 2014. TIVAP-related infections were confirmed in 68
      patients (45%). Demographic characteristics were similar between patients with
      and without TIVAP-related infections. SOFA score on admission per point increase
      [odd ratio (OR), 0.86 interval confidence (IC) 95% (0.8-0.9), p < 0.01] and local
      signs of infection [OR 4.0, IC 95% (1.1-15.6), p = 0.04] were significantly
      associated with TIVAP-related infection. Patients with TIVAP-related infection
      had lower ICU and 6-month mortality as compared to their counterparts (9 vs. 40%,
      respectively, p < 0.01; and 50 vs. 66%, respectively, p = 0.04). TIVAP-related
      infection was significantly associated with ICU survival [OR 0.2, IC 95% (0.05
      0.5), p < 0.01]. CONCLUSIONS: TIVAP-related infection was confirmed in nearly one
      out of two cases of life-threatening sepsis in patients in whom it has been
      removed. TIVAP-related infection was associated with a good prognosis, as
      compared to patients with other causes of infection.

PMID- 29594892
TI  - Hormesis and paradoxical effects of pea (Pisum sativum L.) parameters upon
      exposure to formaldehyde in a wide range of doses.
AB  - Formaldehyde is a widespread pollutant of soil near roads including agricultural
      lands. Non-monotonic changes (hormesis and paradoxical effects) in chlorophyll
      (Ch) and carotenoid (Car) contents, the lipid peroxidation (LP) rate in plant
      leaves and growth parameters (GP) of plants can be caused by various pollutants.
      Hormesis is a biphasic dose-response phenomenon, characterised by low-dose
      stimulation and high-dose inhibition. The remaining types of non-monotonic
      responses are classified as paradoxical effects. While most authors who have
      studied formaldehyde and plants considered gaseous exposure to shoots, the effect
      of this pollutant in soil solution has been poorly examined. Thus, we studied the
      non-monotonic changes in Ch and Car contents, LP rate and GP in pea (Pisum
      sativum L.) upon exposure to formaldehyde in solution, at a wide range of
      sublethal concentrations from 0.063 * 10-2 to 0.16 g L-1. With formaldehyde
      exposure, LP and Ch contents had paradoxical effects (triphasic and multiphase
      changes, accordingly), while Car level did not change and GP exhibited a hormetic
      response. The date showed that pea parameters display diverse types of non
      monotonic responses upon exposure to the same formaldehyde concentrations. High
      pollutant concentrations (0.08-0.16 g L-1) increased LP and significantly
      decreased GP (to 2.3-2.5 times compared to the control), while the Ch content was
      increased. Lower concentrations (<0.08 g L-1) caused a moderate deviation in all
      parameters from the control (not more than 62%) for hormesis and paradoxical
      effects.

PMID- 29594893
TI  - The association between high-density lipoproteins and estimated glomerular
      filtration rate in patients without severe kidney disease.
AB  - PURPOSE: Several studies investigated the association between the estimated
      glomerular filtration rate (eGFR) and the concentration of high-density
      lipoproteins (HDL) in patients without severely damaged kidney function. As
      results of those studies were inconclusive and contradictory, we wanted to
      investigate this association in multiple cardiovascular disease (CVD) risk
      patients without severe kidney disease or renal failure. METHODS: We enrolled a
      cohort of 187 patients with intermediate and high CVD risk without severe renal
      disease. We grouped them based on their eGFR into: group 1 (>= 30 < 60
      ml/min/1.73 m2), group 2 (>= 60 < 90 ml/min/1.73 m2) and group 3 (>= 90
      ml/min/1.73 m2). We analyzed the difference between their HDL levels and assessed
      the association of HDL and eGFR in three regression models with the following
      predictors: model 1 (age and gender), model 2 (model 1 plus smoking status, hs
      CRP and diabetes mellitus) and model 3 (model 2 plus excessive weight and
      obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, family history
      of CVD and medications they used). RESULTS: Patients with the lowest eGFR had the
      lowest HDL values (P = 0.013). In multiple linear regression, HDL was an
      independent predictor of eGFR (beta = 0.189, P = 0.025) which was also shown in
      multinomial regression for all three models: model 1 [odds ratio (OR) 0.05; 95%
      confidence interval (CI) 0.007-0.331; P = 0.002], model 2 (OR 0.052; 95% CI 0.006
      0.428; P = 0.006) and model 3 (OR 0.2; 95% CI 0.001-0.309; P = 0.005).
      CONCLUSIONS: Low HDL is an independent predictor of lower eGFR in intermediate
      and high CVD risk patients without severe kidney disease. In such patients, low
      HDL could be one of the early indicators of renal failure.

PMID- 29594894
TI  - Mesenchymal stem cells alleviate acute kidney injury by down-regulating C5a/C5aR
      pathway activation.
AB  - BACKGROUND: Acute kidney injury (AKI) leads to serious renal damage, and early
      inhibition of inflammation is necessary for its treatment. C5a/C5aR signaling
      activation promotes inflammatory response in tissue injury. Anti-inflammatory
      activity of mesenchymal stem cells (MSCs) makes it possible to alleviate AKI by
      controlling the C5a/C5aR signaling activation. METHODS: Ischemia reperfusion
      (I/R)-induced AKI models in wild-type and C5aR KO mice were used. In addition,
      human bone marrow MSCs (hBM-MSCs) or C5aR antagonist were injected in this model.
      All animals were killed at 72 h after reperfusion. In vitro, the LPS-activated
      macrophage line RAW264.7 cells were co-cultured with or without hBM-MSCs in the
      presence of recombinant C5a or not for indicated time points. After that, C5aR
      expression, the inflammatory factor production, and NF-kappaB translocation in
      RAW264.7 cells were measured. RESULTS: hBM-MSC treatment and C5a/C5aR signaling
      blockade or C5aR-deficiency exhibited similar attenuated effects on I/R-induced
      AKI, macrophages infiltration, and the pro-inflammatory cytokines TNF-alpha and
      IL-1beta expression in renal tissues in mice. Moreover, hBM-MSC administration
      led to a significant reduction in C5a levels in serum and C5aR expression in the
      kidney tissues in mice after I/R. In vitro, upon co-culture with hBM-MSCs, both
      C5aR expression and the secretion of pro-inflammatory factors TNF-alpha, IL-6,
      and nitric oxide in LPS-activated macrophages were markedly reduced. Accordingly,
      recombinant complement C5a accelerated LPS-induced NF-kappaB translocation and
      pro-inflammatory factors expression in macrophages, but the addition of hBM-MSCs
      reversed these C5a-induced effects. CONCLUSIONS: The present study indicates that
      hBM-MSCs alleviate AKI via suppressing C5a/C5aR-NF-kappaB pathway activation.

PMID- 29594895
TI  - Clinical implications of CT findings in mesenteric venous thrombosis at
      admission.
AB  - PURPOSE: The main aim of this study was to evaluate the association of computed
      tomography (CT) findings at admission and bowel resection rate in patients with
      mesenteric venous thrombosis (MVT). It was hypothesized that abnormal intestinal
      findings on CT were associated with a higher bowel resection rate. METHODS:
      Retrospective study of MVT patients treated between 2004 and 2017. CT images at
      admission and at follow-up were scrutinized according to a predefined protocol.
      Successful recanalization was defined as partial or complete recanalization of
      the portomesenteric venous thrombosis at the latest CT follow-up (n = 70).
      RESULTS: We studied 102 patients (median age 58 years, 61 men). Lifelong
      anticoagulation was initiated in 64 patients, and bowel resection rate was 17%.
      No referral letter indicated suspicion of MVT, whereas three indicated suspected
      intestinal ischemia. Previous venous thromboembolism was associated with
      increased bowel resection rate (p = 0.049). No patient with acute pancreatitis (n
      = 17) underwent bowel resection (p = 0.068). The presence of mesenteric oedema (p
      = 0.014), small bowel wall oedema (p < 0.001), small bowel dilatation (p =
      0.005), and ascites (p = 0.021) were associated with increased bowel resection
      rate. Small bowel wall oedema remained as an independent risk factor associated
      with bowel resection (OR 15.8 [95% CI 3.2-77.2]). Successful thrombus
      recanalization was achieved in 66% of patients. CONCLUSION: The presence of
      abnormal intestinal findings secondary to MVT confers an excess risk of need of
      bowel resection due to infarction. Responsible physicians should therefore
      scrutinize the CT images at diagnosis together with the radiologist to better
      tailor clinical surveillance.

PMID- 29594896
TI  - In Defence of Moral Pluralism and Compromise in Health Care Networks.
AB  - The organisation of health care is rapidly changing. There is a trend to move
      away from individual health care institutions towards transmural integrated care
      and interorganizational collaboration in networks. However, within such
      collaboration and network there is often likely to be a pluralism of values as
      different health care institutions often have very different values. For this
      paper, we examine three different models of how we believe institutions can come
      to collaborate in networks, and thus reap the potential benefits of such
      collaboration, despite having different moral beliefs or values. A first way is
      the pragmatic way in which the different health care institutions avoid ethical
      reflection and focus on solutions. A second possible route is that of consensus
      where health care institutions base their collaboration on values that they all
      share. The third, and final, approach is that of compromise. Although moral
      compromise is often seen in a negative light, we argue that in many cases
      compromise might be necessary and ethically justified. In a final section, we
      will shift our focus from discussing various theoretical methods to allow
      collaboration to the potential content of consensus or compromise.

PMID- 29594897
TI  - Eco-toxicology effect on Moina mongolica Daday exposed to Cd2+, Pb2+, and Hg2+ by
      the food chain.
AB  - As one of the most important contaminants, heavy metals can seriously influence
      human health via the food chain. In this study, the eco-toxicological effects of
      Cd2+, Pb2+, and Hg2+ on Moina mongolica Daday were investigated by feeding them
      Chlorella sp. that contained heavy metals. The relative body lengths of the M.
      mongolica changed rapidly, peaking at 2 days for Hg2+, 6 days for Cd2+, and 8
      days for Pb2+. Moreover, grazing and clearance rates of the experimental group
      were apparently lower than those of the control group after immersion in heavy
      metals. Additionally, Cd2+ and Pd2+ in the food significantly influenced the mean
      lifespan of M. mongolica of the P and F1 generations. Egg production per brood
      was also significantly impacted by Cd2+ and Pb2+ in the food in generation P.
      Interestingly, Pb2+ was the only metal that significantly influenced the
      reproduction times of F2, while the reproductive times were significantly
      influenced by Cd2+ for generation P. Moreover, Cd2+, Pb2+, and Hg2+ in the food
      significantly influenced the fecundity of generation P. Evaluation of the
      population growth parameters of M. mongolica revealed that the intrinsic rate of
      increase, net reproduction rate, and finite rate of increase were significantly
      influenced by Cd2+, Pb2+, and Hg2+ in the food in generation P. Additionally,
      Hg2+ slightly impacted generation time for generation P. Finally, the acute
      toxicity toward M. mongolica was Hg2+ > Cd2+ > Pb2+. Overall, heavy metals in the
      food were likely to influence the growth, survival, and population growth of M.
      mongolica through the food chain.

PMID- 29594898
TI  - Estimation of physicochemical properties of 2-ethylhexyl-4-methoxycinnamate
      (EHMC) degradation products and their toxicological evaluation.
AB  - The organic UV filters, commonly used in personal protection products, are of
      concern because of their potential risk to aquatic ecosystems and living
      organisms. One of UV filters is ethylhexyl-4-methoxycinnamate (EHMC) acid.
      Studies have shown that, in the presence of oxidizing and chlorinating factors,
      EHMC forms a series of products with different properties than the substrate. In
      this study, the toxicities of EHMC and its transformation/degradation products
      formed under the influence of NaOCl/UV and H2O2/UV systems in the water medium
      were tested using Microtox(r) bioassay and by observation of mortality of
      juvenile crustaceans Daphnia magna and Artemia Salina. We have observed that
      oxidation and chlorination products of EHMC show significantly higher toxicity
      than EHMC alone. The toxicity of chemicals is related to their physicochemical
      characteristic such as lipophilicity and substituent groups. With the increase in
      lipophilicity of products, expressed as log KOW, the toxicity (EC50) increases.
      On the basis of physicochemical properties such as vapour pressure (VP),
      solubility (S), octanol-water partition coefficient (KOW), bioconcentration
      factor (BCF) and half-lives, the overall persistence (POV) and long-range
      transport potential (LRTP) of all the products and EHMC were calculated. It was
      shown that the most persistent and traveling on the long distances in environment
      are methoxyphenol chloroderivatives, then methoxybenzene chloroderivatives, EHMC
      chloroderivatives, methoxybenzaldehyde chloroderivatives and methoxycinnamate
      acid chloroderivatives. These compounds are also characterised by high toxicity.

PMID- 29594899
TI  - An evaluation of stabilised/solidified contaminated model soil using PC-based and
      MgO-based binders under semi-dynamic leaching conditions.
AB  - The leaching performance of stabilised/solidified contaminated model soil was
      studied to investigate the benefit of stabilisation/solidification treatment
      using novel binders over conventional binders. Different combinations of Portland
      cement (PC), ground granulated blast-furnace slag (GGBS), pulverised fly ash
      (PFA), and magnesia (MgO) were used and grouped into PC-based and MgO-based
      binders. A semi-dynamic leaching test was used, where the cumulative releases of
      Zn, Cu, Ni, Pb, Ca, and Mg were measured and the effective diffusion coefficients
      (De) and the leachability indices (LX) were calculated. The effects of different
      binders and water/cement ratios (w/c) on the migration of different metals after
      treatment were also discussed. The results showed that w/c ratio has a
      significant impact on the cumulative leachability of heavy metals. The diffusion
      coefficients of Pb and Zn are higher than those of Cu and Ni. In addition, mixes
      (w/c at 0.5:1) showed better performance in immobilising heavy metals than mixes
      (w/c at 1:1), especially in the case of Cu, Ni, and Pb.

PMID- 29594900
TI  - Study on hydrothermal deactivation of Pt/MnO x -CeO2 for NO x -assisted soot
      oxidation: redox property, surface nitrates, and oxygen vacancies.
AB  - The study mainly focuses on surface properties to investigate the deactivation
      factors of Pt/MnO x -CeO2 by H2 temperature-programmed reduction, CO chemical
      adsorption, NO x -temperature-programmed desorption (TPD), O2-TPD, NO temperature
      programmed oxidation, SEM, TEM, in situ diffuse reflectance infrared Fourier
      transform spectra, Raman, and thermogravimetric methods. The results show that
      there are three main factors to lead to hydrothermal deactivation of the
      catalyst: redox property, oxygen vacancy, and surface nitrates. The loss of
      oxygen vacancies decreases the generation and desorption of active oxygen and
      that of surface nitrates weakens the production of NO2 and surface peroxides (-O2
      ). These factors greatly result in the damage of the C-NO2-O2 cooperative
      reaction.

PMID- 29594901
TI  - Effect of humic and fulvic acid transformation on cadmium availability to wheat
      cultivars in sewage sludge amended soil.
AB  - The high nutrients and organic matter (OM) content of sewage sludge make it an
      excellent fertilizer to enhance soil fertility and crop production. However, the
      presence of adsorbed and precipitated forms of heavy metals, especially cadmium
      (Cd), can be a major problem for such a utilization of sludge. This pot study
      aims at producing safe food with minimal Cd concentrations from sewage sludge
      amended soils. Two wheat cultivars (NARC-11 and Shafaq-06) were sown in soil
      amended with sewage sludge with rates 0, 15 and 30 g kg-1 soil. Application of
      sewage sludge resulted in enhancement of wheat grain yield while Cd
      concentrations in wheat grains of both cultivars remained within permissible
      limits (24.1 to 58.6 MUg kg-1 dry weight). Fourier transform infrared (FTIR)
      spectroscopic analysis revealed more spectral changes in fulvic acids than in
      humic acids, which showed a higher humification degree, making them chemically
      and biologically more stable for Cd retention. Sequential extraction data of Cd
      after NARC-11 harvest exhibited a significant decrease in mobile fractions
      (exchangeable and reducible fractions were reduced by 3.6 and 5.2%, respectively)
      and increase in immobile fraction (the oxidizable and residual fractions
      increased by 7 and 1.8%, respectively). It is concluded that sewage sludge
      application could be useful for the improvement of wheat production due to
      formation of stable humate complexes and decrease in Cd availability.

PMID- 29594903
TI  - A predictive analysis of CO2 emissions, environmental policy stringency, and
      economic growth in China.
AB  - This study takes environmental policy stringency and economic activity as the
      controlling variables and forecasts the CO2 emissions in China up to 2022. In
      doing so, an application of corrected grey model with convolution is used over
      the annual time series data between 1990 and 2012. The simulation results show
      that (1) between 2012 and 2022, CO2 emissions in China is expected to increase at
      an average rate of 17.46% annually, raising the emissions intensity from 7.04 in
      2012 to 25.461 metric tons per capita by 2022; (2) stringent environmental
      policies reduce CO2 emissions-whereas, GDP tends to increase the emissions
      intensity in China; (3) stringent environmental policies are found to have a
      negative impact on GDP in China. Based on the empirical findings, the study also
      provides some policy suggestions to reduce emissions intensity in China.

PMID- 29594902
TI  - Concentration effects of the UV filter oxybenzone in Cyperus alternifolius:
      assessment of tolerance by stress-related response.
AB  - Phytoremediation has been proposed to reduce the load of the sunscreen oxybenzone
      (OBZ) in the aquatic environment. Despite the proven removal efficiency of this
      compound, little is known about its influence, particularly oxidative stress on
      plants. In this study, a short-term incubation of macrophytic Cyperus
      alternifolius was performed to prove the plant's ability to withstand the stress.
      Detached shoots were immersed in medium spiked with different concentrations of
      OBZ (50, 100, and 500 MUM) for 2, 4, and 7 days, respectively. Increased
      formation of O2- and H2O2 in Cyperus treated with OBZ was characterized by
      intense colorization following histochemical staining. Alterations of enzyme
      activities involved in the antioxidative defense system indicate an adaptive
      response of C. alternifolius to this xenobiotic stress. Quantification of lipid
      peroxidation reveals that no significant membrane damage occurred during
      incubation with OBZ. Overall, 50 MUM OBZ (tenfold higher than the amount
      frequently detected in the environment) exhibited low toxic effects. Accordingly,
      this pilot study provides information on the potential use of Cyperus to remove
      emerging sunscreen contaminants from water bodies.

PMID- 29594904
TI  - Mitigation of Cr(VI) toxicity using Pd-nanoparticles immobilized catalytic
      reactor (Pd-NICaR) fabricated via plasma and gamma radiation.
AB  - Catalytic reduction of Cr(VI) to less toxic Cr(III) form using metal
      nanoparticles is one of the novel approaches adopted to deal with Cr toxicity. In
      this work, we report the fabrication of a facile, reusable, and robust Pd
      nanoparticles-immobilized catalytic reactor (Pd-NICaR) system using green,
      environment-friendly gamma radiolytic, and plasma polymerization processes. A
      room temperature, RF-powered plasma polymerization process was employed to
      functionalize a polyethylene-polypropylene (PE-PP) non-woven matrix with epoxy
      group containing monomer 2,3-epoxypropyl methacrylate (EPMA). EPMA-functionalized
      PE-PP (EPMA-f-PE-PP) substrate was subsequently used as a template for in situ
      generation and immobilization of Pd NPs via gamma radiolytic route. The samples
      were characterized using FTIR, SEM, XPS, and XRF techniques. The catalytic
      efficacy of Pd-NICaR towards Cr(VI) reduction, in the presence of formic acid
      (FA) as a reductant, was investigated spectrophotometrically, and reaction
      parameters were optimized at reaction temperature of 50  degrees C and
      [FA]/[Cr(VI)] = 680 to achieve catalytic reduction efficiency of 99.7% within 10
      min in batch process. The system showed excellent reusability (~ 20 cycles) and
      storage stability (> 30 days) without substantial loss (~ 11%) of activity.
      Practical applicability of the robust catalytic system towards Cr(VI) toxicity
      mitigation was established in continuous flow mode using a fixed-bed column
      reactor.

PMID- 29594905
TI  - Identification of the main mechanisms involved in the tolerance and
      bioremediation of Cr(VI) by Bacillus sp. SFC 500-1E.
AB  - Chromium pollution is a problem that affects different areas worldwide and,
      therefore, must be solved. Bioremediation is a promising alternative to treat
      environmental contamination, but finding bacterial strains able to tolerate and
      remove different contaminants is a major challenge, since most co-polluted sites
      contain mixtures of organic and inorganic substances. In the present work,
      Bacillus sp. SFC 500-1E, isolated from the bacterial consortium SFC 500-1 native
      to tannery sediments, showed tolerance to various concentrations of different
      phenolic compounds and heavy metals, such as Cr(VI). This strain was able to
      efficiently remove Cr(VI), even in the presence of phenol. The detection of the
      chrA gene suggested that Cr(VI) extrusion could be a mechanism that allowed this
      strain to tolerate the heavy metal. However, reduction through cytosolic NADH
      dependent chromate reductases may be the main mechanism involved in the
      remediation. The information provided in this study about the mechanisms through
      which Bacillus sp. SFC 500-1E removes Cr(VI) should be taken into account for the
      future application of this strain as a possible candidate to remediate
      contaminated environments.

PMID- 29594906
TI  - Simultaneous determination of sulfonamides and fluoroquinolones from
      environmental water based on magnetic double-template molecularly imprinting
      technique.
AB  - In this work, a fast and selective method based on magnetic extraction is
      presented for the simultaneous extraction of sulfonamides (SAs) and
      fluoroquinolones (FQs), followed by liquid chromatography-tandem mass
      spectrometry detection. In this method, magnetic surface double-template
      molecularly imprinted polymers (MSdt-MIPs) with superparamagnetic property and
      high selectivity toward both SAs and FQs were synthesized and directly applied to
      the simultaneous extraction of SAs and FQs from environmental water as magnetic
      adsorbents. The extraction and enrichment procedures could be accomplished in one
      single step by stirring the mixture of MSdt-MIPs and water sample, and the MSdt
      MIPs with adsorbed analytes were easily separated from the water sample by a
      magnet afterwards. The adsorption mechanism of MSdt-MIPs was investigated by
      employing the adsorption thermodynamic and kinetic studies, and the selectivity
      of the MSdt-MIPs toward target analytes was evaluated through the selectivity
      test. For validation of the proposed method, the matrix effect was evaluated and
      compared to that of the traditional SPE method. Excellent linearity (R > 0.9990)
      for both SAs and FQs were obtained in the concentration range of 20-2000 ng L-1,
      and the limits of detection are in the range of 3.0-4.7 ng L-1 for SAs while 4.1
      6.1 ng L-1 for FQs. Finally, the proposed method was successfully applied to the
      simultaneous determination of SAs and FQs in several environmental water samples.

PMID- 29594907
TI  - Association between short-term exposure to ambient air pollution and daily
      mortality: a time-series study in Eastern China.
AB  - Few studies were conducted to evaluate health effects of acute exposure to PM2.5
      and daily mortality in Asian countries due to lack of large-scale PM2.5
      monitoring data. We conducted a time-series study to examine the associations of
      short-term exposure to four common air pollutants (PM2.5, PM10, NO2, and SO2) and
      daily mortality in Ningbo, Zhejiang, China. We used generalized addictive model
      (GAM) to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the
      association of these four air pollutants with daily mortality. The study included
      9365 people in the 2-year study period from 2014 to 2015. SO2 were significantly
      associated with risk of NAD, RD, and CD mortality with RRs of 1.034 (95% CI
      1.004, 1.064), 1.067 (95% CI 1.010, 1.127), and 1.049 (95% CI 1.001, 1.098),
      respectively.PM2.5 and PM10 were significantly associated with risk of death from
      NAD mortality in warm season. Similar associations were observed for PM10 (RR =
      1.056, 95% CI 1.004, 1.111) and risk of CD mortality. The study provides further
      evidence that short-term exposure to PM2.5, PM10, NO2, and SO2 are associated
      with increased risk of daily mortality.

PMID- 29594908
TI  - Hematological indicators in pygmy wood mouse Apodemus uralensis (Muridae,
      Rodentia) populations as markers of the environmental radiation exposure: East
      Urals radioactive trace (Russia).
AB  - The hematological effects of chronic radiation exposure in males of the pygmy
      wood mouse (Apodemus uralensis Pall., 1811) from the East Urals radioactive trace
      (EURT) area were assessed, taking into account population abundance and
      reproductive status (immature, ripening, and mature yearlings). For this purpose,
      we analyzed the morpho-functional characteristics of erythrocytes (red cell
      indices [MCV, MCH, MCHC], red cell count, activity of antioxidant enzymes [GSH
      Px, CAT], lipid peroxidation, glycolysis, osmotic resistance, methaemoglobin
      content) and blood plasma components (free hemoglobin, total lipids, total
      cholesterol, and glucose) in the background territory and the EURT area; these
      areas have a density of soil contamination with 90Sr of 12,851 and 198 kBq * m-2,
      respectively (four and two order of magnitude higher than the background value).
      The data indicate the "hyperfunctional" state of the erythrocyte, aimed at
      activation of the gas transport function of blood in the radioactive environment.
      This, as a consequence, determines the insufficiency of energy supply of the cell
      defense system necessary to maintain the structural integrity of the membrane.
      Intensification of membrane lipid peroxidation, reduction of osmotic resistance
      and GSH-Px activity in red cells, an increase in the degree of intravascular
      hemolysis, and tendency towards erythropenia indicate the processes of
      accelerated aging of erythrocytes and their more pronounced destruction in the
      circulatory bed. The level of the hematological response increased with
      increasing radiation burden and was more pronounced with a large population size.
      The interaction effect of "overpopulation" and "radioactive pollution" was
      observed to a lesser degree for ripening males, and was very small for sexually
      mature animals. Immature males from the EURT head part with internal whole-body
      radiation doses of 0.0045-0.35 mGy/day can be considered as the most sensitive
      group to the factors synergy, including radiation damage and overabundance
      population.

PMID- 29594909
TI  - An Attenuated Highly Pathogenic Chinese PRRS Viral Vaccine Confers Cross
      Protection to Pigs against Challenge with the Emerging PRRSV NADC30-Like Strain.
AB  - A novel PRRSV strain was isolated in China that was genetically similar to the
      NADC30 strain which is reported to have spread throughout China. The objective of
      the present study was to evaluate the cross-protective efficacy of the live
      vaccine TJM-F92 in young pigs against challenge with a NADC30-like strain,
      HN201605. Twenty-five PRRSV- and antibody-free pigs were randomly divided into
      the following five groups: Vac/ChA, Unvac/ChA, Vac/ChB, Unvac/ChB and the mock.
      The pigs in groups Vac/ChA and Vac/ChB were inoculated intramuscularly with 1 mL
      TJM-F92 (105.0 TCID50/mL). At 28 days post vaccination (0 days post challenge),
      groups Vac/ChA and Unvac/ChA were inoculated intranasally with 104.5 TCID50/mL
      PRRSV strain TJ F3 (2 mL/pig), while groups Vac/ChB and Unvac/ChB were
      inoculated, using the same route, with the same dose of the NADC30-like strain
      HN201605 F3. Protective effects of the PRRSV strain were observed in all pigs in
      the Vac/ChA and Vac/ChB groups. Neither high fever nor signs of clinical disease
      were observed through the experiment in these groups, whereas pigs in Unvac/ChA
      group exhibited serious clinical symptoms, pathological lesions, and weight loss.
      In Unvac/ChB group, pigs developed milder clinical symptoms, which demonstrated
      that the NADC30-like strain HN201605 had moderate pathogenicity. The results
      suggest that the MLV vaccine strain TJM-F92 is an effective and safe vaccine
      candidate for use in China.

PMID- 29594910
TI  - Synopsis of the species of Ceratomyxa Thelohan, 1892 (Cnidaria, Myxosporea,
      Ceratomyxidae) described between 2007 and 2017.
AB  - A synopsis of the species of Ceratomyxa Thelohan, 1892 (Cnidaria, Myxosporea,
      Ceratomyxidae) described between 2007 and 2017 is presented, including 83 nominal
      species. For each species, the most important morphological and morphometric
      features are indicated in tabulated format. Included are also the site of
      infection within the host, and geographical location, plus a full bibliography of
      the original records of species. Molecular data (GenBank accession numbers) are
      also provided whenever possible.

PMID- 29594911
TI  - Analyzing the Impact of Compliance with National Guidelines for Pancreatic Cancer
      Care Using the National Cancer Database.
AB  - IMPORTANCE: Management of pancreatic cancer is complex, requiring coordination of
      multiple providers. National Comprehensive Cancer Network guidelines, developed
      for standardization and quality improvement, recommend a multimodal approach.
      OBJECTIVE: This study analyzed national rates of compliance with National
      Comprehensive Cancer Network recommendations, assessed factors affecting
      compliance, and evaluated whether compliance with evidence-based guidelines
      improved overall survival. DESIGN: This is a retrospective review of adults
      diagnosed with pancreatic cancer entered into the National Cancer Database.
      Patients included had stage I and II pancreatic cancer, and complete data in the
      database. Patients were classified as compliant if they underwent both surgery
      and a second treatment modality (chemotherapy, radiation, or chemoradiation).
      Clinico-pathologic variables were analyzed using univariate and multivariate
      models to predict overall survival. SETTING: Hospital-based national study
      population. PARTICIPANTS: Patients with stage I or II pancreatic cancer. MAIN
      OUTCOMES AND MEASURES: Compliance with National Comprehensive Cancer Network
      recommendations, factors affecting compliance, and overall survival based on
      compliance. RESULTS: A total of 52,450 patients were included; 19,272 patients
      (37%) were compliant. Patients were found to be most compliant in the 50-59-year
      old range (49% complaint), with decreased compliance at the extremes of age. Male
      patients were more compliant than female patients (39 vs 34%, p < 0.0001).
      Caucasians were more compliant (39%) than African Americans (32%) or other races
      (32%, p < 0.0001). Patients treated at academic/research centers were more
      compliant than patients treated at other facilities (39% compliant, p < 0.0001).
      Patients with stage II disease were more compliant compared with stage I disease
      (43 vs 18%, p < 0.0001). Compliance was shown to improve overall survival (p <
      0.0001). CONCLUSION: Adherence to National Comprehensive Cancer Network
      guidelines for pancreatic cancer patients improves survival. Compliance
      nationwide is low, especially for older patients and minorities and those treated
      outside academic centers. More studies will need to be performed to identify
      factors that hinder compliance.

PMID- 29594912
TI  - Long-Term Oncologic Outcomes of Minimally Invasive Proctectomy for Rectal
      Adenocarcinoma.
AB  - BACKGROUND: Long-term oncologic outcomes after minimally invasive surgery (MIS)
      for rectal adenocarcinoma compared to open surgery continue to be debated. We
      aimed to review our high-volume single-institution outcomes in MIS rectal cancer
      surgery. METHODS: A retrospective review of a prospectively collected database
      was completed of all consecutive adult patients with rectal adenocarcinoma
      treated from January 2005 through December 2011. Stage IV or recurrent disease
      was excluded. Demographics and operative and pathologic details were reviewed and
      reported. Primary endpoints include survival and recurrence. RESULTS: A total of
      324 patients were included and median follow-up was 54 months (IQR = 37.0, 78.8).
      The mean age was 58.2 +/- 14.1 years. Tumors were in the upper rectum in 111
      patients, mid-rectum in 113 patients, and lower rectum in 100 patients. Stage III
      disease was most common (49.4%). Overall conversion to open procedure rate was
      13.9%. The circumferential radial margin was positive in only 1 patient (0.3%)
      and the mean lymph node yield was 24.7 +/- 17.2. Cancer recurred in 42 patients
      (13%), 10 (2.5%) patients developed local recurrence, 32 (9.8%) developed distant
      metastasis, and 2 (0.6%) patients had both. The 5-year overall survival for stage
      0, 1, 2, and 3 disease is 96, 91, 80, and 77%, respectively (p = 0.015).
      CONCLUSION: In carefully selected rectal cancer patients treated with MIS, long
      term outcomes of survival and recurrence appear to compare favorably to
      previously published series.

PMID- 29594913
TI  - Collapsing Polypoid Cysts of the Sigmoid.

PMID- 29594914
TI  - Polymer-wrapped single-walled carbon nanotubes: a transformation toward better
      applications in healthcare.
AB  - Carbon nanotubes (CNTs) possess outstanding properties that could be useful in
      several technological, drug delivery, and diagnostic applications. However, their
      unique physical and chemical properties are hindered due to their poor
      solubility. This article review's the different ways and means of solubility
      enhancement of single-wall carbon nanotubes (SWNTs). The advantages of SWNTs over
      the multi-walled carbon nanotubes (MWNTs) and the method of non-covalent
      modification for solubility enhancement has been the key interest in this review.
      The review also highlights a few examples of dispersant design. The review
      includes some interesting utility of SWNTs being wrapped with polymer especially
      in biological media that could mediate proper drug delivery to target cells.
      Further, the use of wrapped SWNTs with phospholipids, nucleic acid, and
      amphiphillic polymers as biosensors is of research interest. The review aims at
      summarizing the developments relating to wrapped SWNTs to generate further
      research prospects in healthcare.

PMID- 29594915
TI  - Role of cardiac 123I-mIBG imaging in predicting arrhythmic events in stable
      chronic heart failure patients with an ICD.
AB  - BACKGROUND: Despite therapeutic improvement, the prognosis of chronic heart
      failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac
      death (SCD). This prospective study evaluated myocardial 123I-meta
      iodobenzylguanidine (123I-mIBG) scintigraphy as a predictor of arrhythmic events
      (AE) in CHF patients. METHODS: 170 CHF patients referred for implantable
      cardioverter-defibrillator (ICD) implantation for both primary and secondary
      prevention were enrolled. All patients underwent planar and SPECT imaging. Early
      and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO), early and late
      summed SPECT scores were calculated The primary endpoint was an AE: sustained
      ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or
      SCD. The secondary endpoint was appropriate ICD therapy. RESULTS: During a median
      follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS)
      was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on
      only patients with an ICD for primary prevention, ESS was the only independent
      predictor of AE [HR 1.028 (1.007-1.050)]. 123I-mIBG-derived parameters failed to
      be independent predictors of appropriate ICD therapy. However there was a "bell
      shaped" relation between 123I-mIBG scintigraphy-derived parameters and AE and
      appropriate ICD therapy, i.e., those with intermediate 123I-mIBG abnormalities
      tended to be at higher risk of events. CONCLUSION: Although SPECT 123I-mIBG
      scintigraphy was associated with AE in CHF patients with ICD implantation for
      primary and secondary prevention, no association was found between 123I-mIBG
      scintigraphy-derived parameters and appropriate ICD therapy.

PMID- 29594916
TI  - Calcifying Odontogenic Cyst Showing a Varied Epithelial Lining: An Additional
      Case with Implications for the Divergent Differentiation Capacity of the Cyst
      Epithelium.

PMID- 29594917
TI  - Seromucinous Hamartoma of the Nasal Cavity.
AB  - Seromucinous hamartoma (SMH) is a rare benign epithelial proliferation occurring
      in the sinonasal tract. The clinical, radiographic, and histologic appearance of
      SMH may mimic several benign and malignant entities. Presented is a novel case,
      with a review of the literature focused on potential histologic diagnostic
      pitfalls.

PMID- 29594918
TI  - Squamous Cell Papillomatosis in the Setting of Recurrent Respiratory
      Papillomatosis.
AB  - A 23 year old male presented to the Otolaryngology clinic with 6 months of
      hoarseness and poor voice projection without improvement from speech therapy or
      medical anti-reflux medication. Upon examination he was found to have multiple
      polypoid lesions emanating from bilateral false vocal folds, left true vocal
      fold, and the anterior commissure. Biopsy and potassium titanyl phosphate (KTP)
      laser ablation with bevacizumab injection provided treatment and confirmed the
      clinical suspicion of squamous cell papilloma. Despite 3 years of treatment, the
      papillomatosis proved difficult to control, requiring a procedure approximately
      every 3 months. In an attempt to control the course of the disease the patient
      received a series of three bevacizumab and three cidofovir injections. Serial
      biopsies showed mild atypia within the squamous cell papillomas. Two separate
      biopsies confirmed presence of human papillomavirus (HPV) 6/11 via in situ
      hybridization with appropriate controls. There is promising research that the
      quadrivalent HPV (types 6, 11, 16, and 18) vaccine both reduces the disease
      burden in patients with active disease and reduces the incidence of recurrent
      respiratory papillomatosis (RRP). Other studies have shown that local immunologic
      dysregulation may play a role in RRP pathogenesis. Therefore new treatment
      options, to include PDL-1 blockade, offer hope in treating this benign condition
      with high morbidity and rare mortality.

PMID- 29594919
TI  - Chemometric evaluation of heavy metal pollutions in Patna region of the Ganges
      alluvial plain, India: implication for source apportionment and health risk
      assessment.
AB  - While metal pollution and distribution in soil are well documented for many
      countries, the situation is more serious in developing countries because of the
      rapid increase in industrialization and urbanization during last decades.
      Although it is well documented in developed countries, data about substantial
      metal pollution in Indian soil, especially in eastern Ganges alluvial plain
      (GAP), are limited. In this study, eight different blocks of Patna district
      located in eastern GAP were selected to investigate the contamination,
      accumulation, and sources of metals in surface soil considering different land
      use types. Additionally, human health risk assessment was estimated to mark the
      potential carcinogenic and non-carcinogenic effect of metals in soil. The
      concentration of all metals (except Pb) in soil was below the Indian standard
      limit of the potential toxic element for agricultural soil. Pb was the most
      abundant in soil, followed by Zn and Cu, and accounted for 52, 33 and 8% of the
      total metal. In terms of land use types, roadside soil detected higher
      concentrations of all metals, followed by park/grassland soil. Principal
      component analysis results indicated traffic pollution and industrial emissions
      are the major sources of heavy metals in soil. This was further confirmed by
      strong inter-correlation of heavy metals (Cd, Cr, Ni, Cu and Pb). Human health
      risk assessment results indicated ingestion via soil as the primary pathway of
      heavy metal exposure to both adults and children population. The estimated hazard
      index was highest for Pb, suggesting significant non-carcinogenic effect to both
      adults and children population. The children were more prone to the non
      carcinogenic effect of Pb than adults. However, relatively low cancer risk value
      estimated for all metals suggested non-significant carcinogenic risk in the soil.

PMID- 29594920
TI  - Wuhan large pig roundworm virus identified in human feces in Brazil.
AB  - We report here the complete genome sequence of a bipartite virus, herein denoted
      WLPRV/human/BRA/TO-34/201, from a sample collected in 2015 from a two-year-old
      child in Brazil presenting acute gastroenteritis. The virus has 98-99% identity
      (segments 2 and 1, respectively) with the Wuhan large pig roundworm virus
      (unclassified RNA virus) that was recently discovered in the stomachs of pigs
      from China. This is the first report of a Wuhan large pig roundworm virus
      detected in human specimens, and the second genome described worldwide. However,
      the generation of more sequence data and further functional studies are required
      to fully understand the ecology, epidemiology, and evolution of this new
      unclassified virus.

PMID- 29594921
TI  - Bortezomib maintenance therapy in transplant-ineligible myeloma patients who
      plateaued after bortezomib-based induction therapy: a multicenter phase II
      clinical trial.
AB  - In the era of novel therapeutic agents for multiple myeloma (MM), both the
      significance of achieving the plateau phase and the efficacy of subsequent
      maintenance therapy remain unclear. In the present study, we evaluated the
      efficacy and safety of bortezomib maintenance therapy (biweekly for 1 year) in
      transplant-ineligible MM patients who plateaued after bortezomib-based induction
      therapy. Of 36 evaluable patients, the overall response rate during induction
      therapy was 61%, with a stringent complete response in 6%, a complete response in
      6%, a very good partial response in 17%, and a partial response in 33%. Twenty
      patients achieved the plateau phase and subsequently received bortezomib
      maintenance therapy. Median progression-free survival from the induction and
      maintenance therapies was 13.8 months (95% confidence interval, 11.4-23.7 months)
      and 10.7 months (95% confidence interval, 3.7-10.7 months), respectively. During
      maintenance therapy, there were no cases with grade >= 2 peripheral neuropathy,
      nor was there any improvement in the quality of the response. In conclusion,
      although maintenance therapy with biweekly bortezomib for up to 1 year was
      feasible, plateau-oriented bortezomib induction therapy followed by bortezomib
      maintenance therapy was not adequate in newly diagnosed transplant-ineligible MM
      patients.

PMID- 29594922
TI  - Intensification of induction therapy and prolongation of maintenance therapy did
      not improve the outcome of pediatric Langerhans cell histiocytosis with single
      system multifocal bone lesions: results of the Japan Langerhans Cell
      Histiocytosis Study Group-02 Protocol Study.
AB  - Langerhans cell histiocytosis (LCH) with single-system (SS) multifocal bone (MFB)
      lesions is rarely fatal, but patients may experience relapses and develop LCH
      associated sequelae. To evaluate effect on outcomes of pediatric multifocal LCH,
      we tested a treatment protocol modified from the Japan Langerhans Cell
      Histiocytosis Study Group (JLSG)-96 study. We assessed the outcomes of all
      consecutive newly diagnosed pediatric patients with LCH with SS-MFB lesions who
      were treated with JLSG-02 protocol in 2002-2009. JLSG-02 was modified from JLSG
      96 as follows: increased prednisolone dosage at the induction phase and extension
      of maintenance therapy duration from 24 to 48 weeks. In total, 82 patients with a
      median follow-up duration of 8.0 years were eligible for analysis. At 6 weeks,
      92.7% responded to induction; however, 27.6% of responders experienced relapses.
      In total, 4.8% developed central nervous system-related sequelae, including
      central diabetes insipidus and neurodegeneration, which were associated with
      relapse. None of the patients died. The 5-year event-free survival rates were not
      different between JLSG-02 and -96 cohort (66.7 vs. 65.1%; p = 0.697).
      Modification of previous treatment protocol did not contribute to improvement of
      outcomes in LCH with SS-MFB lesions.

PMID- 29594923
TI  - Perioperative safety and hemostatic efficacy of Advate(r) in patients with
      hemophilia A in a postmarketing surveillance in Japan.
AB  - Rurioctocog alfa (recombinant factor VIII: Advate(r)) is available for the
      control of bleeding among patients with hemophilia A in Japan. To evaluate the
      perioperative safety and hemostatic efficacy of Advate(r), a postmarketing
      surveillance was conducted in Japanese patients undergoing surgery in a real
      world setting. A total of 74 surgical procedures performed in 58 subjects aged 0
      75 years, including three females, were studied. A hemostatic efficacy rating of
      "excellent" or "good" was reported in 73/74 surgical procedures (98.6%).
      Perioperative bleeding was successfully controlled by Advate(r) in five subjects
      with positive FVIII inhibitors (2.4-9.1 BU/mL). Advate(r) was administered at
      higher initial bolus doses (114-385 IU/kg) and at higher rates by subsequent
      initial continuous infusion (8.3-15 IU/kg/hour) in the five subjects with
      inhibitor than in the subjects without inhibitor (n = 47; mean initial bolus
      dose: 53.4 IU/kg; subsequent mean initial continuous infusion: 3.8 IU/kg/h).
      Adverse drug reactions were reported in 7/74 (9.5%) procedures, two of which were
      the development of de novo FVIII inhibitors. Overall, the perioperative use of
      Advate(r) in a real-world setting was found to be safe and effective among
      Japanese patients with hemophilia A.

PMID- 29594924
TI  - Hydrodynamic interaction of a self-propelling particle with a wall : Comparison
      between an active Janus particle and a squirmer model.
AB  - Using lattice Boltzmann simulations we study the hydrodynamics of an active
      spherical particle near a no-slip wall. We develop a computational model for an
      active Janus particle, by considering different and independent mobilities on the
      two hemispheres and compare the behaviour to a standard squirmer model. We show
      that the topology of the far-field hydrodynamic nature of the active Janus
      particle is similar to the standard squirmer model, but in the near-field the
      hydrodynamics differ. In order to study how the near-field effects affect the
      interaction between the particle and a flat wall, we compare the behaviour of a
      Janus swimmer and a squirmer near a no-slip surface via extensive numerical
      simulations. Our results show generally a good agreement between these two
      models, but they reveal some key differences especially with low magnitudes of
      the squirming parameter [Formula: see text]. Notably the affinity of the
      particles to be trapped at a surface is increased for the active Janus particles
      when compared to standard squirmers. Finally, we find that when the particle is
      trapped on the surface, the velocity parallel to the surface exceeds the bulk
      swimming speed and scales linearly with [Formula: see text].

PMID- 29594926
TI  - There Are Indeed More Left-Handers Within the Autism Spectrum Disorder Compared
      with in the General Population, but the Many Mixed-Handers Is the More
      Interesting Finding.
AB  - Letter to the editor in response to Howard Kushner's claims that our data on non
      right-handedness within the autism spectrum disorder were organized, by sleight
      of hand, so they would give a significant result that would support our desired
      conclusion. Here, we have re-categorized our data, and present evidence that
      there are indeed more left-handers within the ASD. Furthermore, we refute claims
      that we have misinterpreted our results in order to conclude about a causal link
      between left-handedness and ASD, and highlight our original suggestion that mixed
      handedness, more specifically unclear handedness, is the bigger problem, and that
      our findings of a total 60% non-right-handedness was the more interesting
      finding.

PMID- 29594925
TI  - Deviations from Typical Developmental Trajectories Detectable at 9 Months of Age
      in Low Risk Children Later Diagnosed with Autism Spectrum Disorder.
AB  - This study was designed to track the developmental trajectory, during the first
      24 months of life, of 335 low-risk infants later diagnosed with Autism Spectrum
      Disorder and identify early deviations observed in routine Well Care checkups. We
      compared their achievements to typically developing children and to children
      later diagnosed with non-autistic developmental impairments. The results show
      that in the first 6 months, the children with autism showed normal acquisition of
      milestones, whereas by 9 months of age they began to fail the
      language/communication, as well as motor items when compared to typical and
      delayed non-autistic children. Regular check-up visits may be useful in detecting
      early failure in achieving milestones, leading to earlier referral for further
      evaluation and treatment.

PMID- 29594927
TI  - Differences between immunodeficient mice generated by classical gene targeting
      and CRISPR/Cas9-mediated gene knockout.
AB  - Immunodeficient mice are widely used for pre-clinical studies to understand
      various human diseases. Here, we report the generation of four immunodeficient
      mouse models using CRISPR/Cas9 system without inserting any foreign gene
      sequences such as NeoR cassettes and their characterization. By eliminating any
      possible effects of adding a NeoR cassette, our mouse models may allow us to
      better elucidate the in vivo functions of each gene. Our FVB-Rag2-/-, B6-Rag2-/-,
      and BALB/c-Prkdc-/- mice showed phenotypes similar to those of the earlier
      immunodeficient mouse models, including a lack of mature B cells and T cells and
      an increase in the number of CD45+DX-5+ natural killer cells. However, B6-Il2rg-/
      mice had a unique phenotype, with a lack of mature B cells, increased number of
      T cells, and decreased number of natural killer cells. Additionally, serum
      immunoglobulin levels in all four immunodeficient mouse models were significantly
      reduced when compared to those in wild-type mice with the exception of IgM in B6
      Il2rg-/- mice. These results indicate that our immunodeficient mouse models are a
      robust tool for in vivo studies of the immune system and will provide new
      insights into the variation in phenotypic outcomes resulting from different gene
      targeting methodologies.

PMID- 29594928
TI  - 1H, 13C and 15N resonance assignments for a chemokine receptor-binding domain of
      FROUNT, a cytoplasmic regulator of chemotaxis.
AB  - FROUNT is a cytoplasmic protein that interacts with the membrane-proximal C
      terminal regions (Pro-Cs) of the CCR2 and CCR5 chemokine receptors. The
      interactions between FROUNT and the chemokine receptors play an important role in
      the migration of inflammatory immune cells. Therefore, FROUNT is a potential drug
      target for inflammatory diseases. However, the structural basis of the
      interactions between FROUNT and the chemokine receptors remains to be elucidated.
      We previously identified the C-terminal region (residues 532-656) of FROUNT as
      the structural domain responsible for the Pro-C binding, referred to as the
      chemokine receptor-binding domain (CRBD), and then constructed its mutant,
      bearing L538E/P612S mutations, with improved NMR spectral quality, referred to as
      CRBD_LEPS. We now report the main-chain and side-chain 1H, 13C, and 15N resonance
      assignments of CRBD_LEPS. The NMR signals of CRBD_LEPS were well dispersed and
      their intensities were uniform on the 1H-15N HSQC spectrum, and thus almost all
      of the main-chain and side-chain resonances were assigned. This assignment
      information provides the foundation for NMR studies of the three-dimensional
      structure of CRBD_LEPS in solution and its interactions with chemokine receptors.

PMID- 29594929
TI  - 1H, 13C and 15N backbone NMR chemical shift assignments of the C-terminal P4
      domain of Ahnak.
AB  - Ahnak is a ~ 700 kDa polypeptide that was originally identified as a tumour
      related nuclear phosphoprotein, but later recognized to play a variety of diverse
      physiological roles related to cell architecture and migration. A critical
      function of Ahnak is modulation of Ca2+ signaling in cardiomyocytes by
      interacting with the beta subunit of the L-type Ca2+ channel (CaV1.2). Previous
      studies have identified the C-terminal region of Ahnak, designated as P3 and P4
      domains, as a key mediator of its functional activity. We report here the nearly
      complete 1H, 13C and 15N backbone NMR chemical shift assignments of the 11 kDa C
      terminal P4 domain of Ahnak. This study lays the foundations for future
      investigations of functional dynamics, structure determination and interaction
      site mapping of the CaV1.2-Ahnak complex.

PMID- 29594930
TI  - Stability of the electroosmotic flow of a two-layer electrolyte-dielectric system
      with external pressure gradient?.
AB  - The stability of the electroosmotic flow of electrolyte-dielectric viscous
      liquids under the influence of the DC and AC electric fields along with the
      external pressure gradient is studied theoretically. Liquids are bounded by two
      infinite parallel plates. The lower wall bordering the electrolyte is assumed to
      be a charged surface, and the upper wall is electrically isolated. The charge at
      the lower boundary is assumed to be immobile, while the surface charge at the
      free surface is assumed to be mobile. In this paper, we study the micro- and
      nanosized liquid layers. The mathematical model is described by a nonlinear
      system of the Nernst-Planck-Poisson-Stokes partial differential equations with
      the appropriate boundary conditions on the solid surface, the
      electrolyte/dielectric interface, and on the upper wall. The pressure gradient is
      highly important for the stability of the flow. For the DC case, the external
      pressure could either stabilize and destabilize the flow depending on the
      relative directions of the electroosmotic flow and the pressure-driven flow. For
      the AC case, the dependence on the value of the external pressure is not
      monotonous for different wave numbers of perturbations, but, as a rule, the
      external pressure destabilizes the flow. As the frequency of the electric field
      increases, the one-dimensional solution of the problem becomes stable.

PMID- 29594931
TI  - Validation of [18F]FLT as a perfusion-independent imaging biomarker of tumour
      response in EGFR-mutated NSCLC patients undergoing treatment with an EGFR
      tyrosine kinase inhibitor.
AB  - BACKGROUND: 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) was proposed as an
      imaging biomarker for the assessment of in vivo cellular proliferation with
      positron emission tomography (PET). The current study aimed to validate [18F]FLT
      as a perfusion-independent PET tracer, by gaining insight in the intra-tumoural
      relationship between [18F]FLT uptake and perfusion in non-small cell lung cancer
      (NSCLC) patients undergoing treatment with a tyrosine kinase inhibitor (TKI). Six
      patients with metastatic NSCLC, having an activating epidermal growth factor
      receptor (EGFR) mutation, were included in this study. Patients underwent
      [15O]H2O and [18F]FLT PET/CT scans at three time points: before treatment and 7
      and 28 days after treatment with a TKI (erlotinib or gefitinib). Parametric
      analyses were performed to generate quantitative 3D images of both perfusion
      measured with [15O]H2O and proliferation measured with [18F]FLT volume of
      distribution (V T ). A multiparametric classification was performed by
      classifying voxels as low and high perfusion and/or low and high [18F]FLT V T
      using a single global threshold for all scans and subjects. By combining these
      initial classifications, voxels were allocated to four categories (low perfusion
      low V T , low perfusion-high V T , high perfusion-low V T and high perfusion-high
      V T ). RESULTS: A total of 17 perfusion and 18 [18F]FLT PET/CT scans were
      evaluated. The average tumour values across all lesions were 0.53 +/- 0.26 mL cm-
      3 min- 1 and 4.25 +/- 1.71 mL cm- 3 for perfusion and [18F]FLT V T ,
      respectively. Multiparametric analysis suggested a shift in voxel distribution,
      particularly regarding the V T : from an average of >= 77% voxels classified in
      the "high V T category" to >= 85% voxels classified in the "low V T category".
      The shift was most prominent 7 days after treatment and remained relatively
      similar afterwards. Changes in perfusion and its spatial distribution were
      minimal. CONCLUSION: The present study suggests that [18F]FLT might be a
      perfusion-independent PET tracer for measuring tumour response as parametric
      changes in [18F]FLT uptake occurred independent from changes in perfusion. TRIAL
      REGISTRATION: Nederlands Trial Register (NTR), NTR3557 . Registered 2 August
      2012.

PMID- 29594932
TI  - Sonography in male infertility: a look beyond the obvious.
AB  - Infertility affects 15-20% of the reproductive age range population; the male
      factor accounts for up to 40-60% of these. With female factor infertility
      catching most of the limelight in research, diagnosis and treatment, the other
      half of the problem has not been duly addressed. Imaging has an important role to
      play in the evaluation of male infertility, especially to identify correctible
      (obstructive) causes. We review the scrotal, trans-rectal sonographic and Doppler
      findings in infertile men to aid in the accurate diagnosis and proper management
      of such patients.

PMID- 29594933
TI  - HPV Self-Sampling for Cervical Cancer Screening Among Ethnic Minority Women in
      South Florida: a Randomized Trial.
AB  - BACKGROUND: Ethnic minority women are at increased risk of cervical cancer. Self
      sampling for high-risk human papillomavirus (HPV) is a promising approach to
      increase cervical screening among hard-to-reach populations. OBJECTIVE: To
      compare a community health worker (CHW)-led HPV self-sampling intervention with
      standard cervical cancer screening approaches. DESIGN: A 26-week single-blind
      randomized pragmatic clinical trial. PARTICIPANTS: From October 6, 2011 to July
      7, 2014, a total of 601 Black, Haitian, and Hispanic women aged 30-65 years in
      need of cervical cancer screening were recruited, 479 of whom completed study
      follow-up. INTERVENTIONS: Participants were randomized into three groups: (1)
      outreach by CHWs and provision of culturally tailored cervical cancer screening
      information (outreach), (2) individualized CHW-led education and navigation to
      local health care facilities for Pap smear (navigation), or (3) individualized
      CHW-led education with a choice of HPV self-sampling or CHW-facilitated
      navigation to Pap smear (self-swab option). MAIN MEASURES: The proportion of
      women in each group whom self-reported completion of cervical cancer screening.
      Women lost to follow-up were considered as not having been screened. KEY RESULTS:
      Of the 601 women enrolled, 355 (59%) were Hispanic, 210 (35%) were Haitian, and
      36 (6%) were non-Haitian Black. In intent-to-treat analyses, 160 of 207 (77%) of
      women in the self-swab option group completed cervical cancer screening versus 57
      of 182 (31%) in the outreach group (aOR 95% CI, p < 0.01) and 90 of 212 (43%) in
      the navigation group (aOR CI, p = 0.02). CONCLUSIONS: As compared to more
      traditional approaches, CHW-facilitated HPV self-sampling led to increased
      cervical cancer screening among ethnic minority women in South Florida. TRIAL
      REGISTRATION: Clinical Trials.gov Identifier: NCT02121548.

PMID- 29594934
TI  - Variability in spousal perceptions of caregiving and its relationship to older
      caregiver health outcomes.
AB  - BACKGROUND: The transition to later-life caregiving roles, especially for couples
      caring for each other, can be rife with ambiguity. The incident discordance in
      spousal perceptions of one another's role and its relationship to mental health
      outcomes have not been well-described. OBJECTIVES: (1) To describe the range of
      daily agreement between older adult spouses' perceptions of care given and care
      received; (2) to explore associations between caregiving agreement and daily
      caregiver depression, anxiety, and marital satisfaction; and (3) to evaluate
      differential effects for male and female caregivers. DESIGN: Cross-sectional,
      ecological assessment (daily diary). PARTICIPANTS: Sample of 191 couples aged 60
      64 (total 5196 daily surveys) drawn from the longitudinal Life and Family
      Legacies study. MAIN MEASURES: During 2011-2012, spouses independently completed
      14 consecutive daily surveys about their mood, marital interactions, and support
      exchanges. Caregiving agreement was defined as the daily ratio of spouse-reported
      care received to self-reported care given. Using generalized linear mixed effect
      modeling, we examined associations between spousal care agreement and outcomes of
      depression, anxiety, and marital satisfaction. KEY RESULTS: Sample data
      demonstrated broad variability in spousal agreement, with couples exhibiting
      substantial disagreement on nearly one-third of couple days (780/2598 days). On
      days where care was exchanged, higher caregiving agreement was associated with
      lower caregiver depression (p < 0.01) and anxiety (p < 0.01) in male caregivers,
      and higher marital satisfaction (p = 0.03) in female caregivers. When care
      recipients reported receiving more support than their spouse reported giving,
      these associations did not persist. CONCLUSIONS: Findings suggest that spousal
      agreement about the amount of care given and received varies broadly and is an
      important consideration for primary care providers who counsel these patients day
      to-day. Furthermore, agreement appears to predict mental health and relationship
      outcomes and should be further evaluated in this growing population of mid-to
      late life adults emerging into caregiving.

PMID- 29594936
TI  - Correction to: Estimation of linear energy transfer distribution for broad-beam
      carbon-ion radiotherapy at the National Institute of Radiological Sciences,
      Japan.
AB  - The original version of this article unfortunately contained a mistake. Figure 2
      was published with fake signals in panels (a) and (b) which are corrected in this
      Erratum. The authors are not responsible for this procedural lapse.

PMID- 29594935
TI  - Diabetes Mellitus as a Risk Factor for Parkinson's Disease: a Molecular Point of
      View.
AB  - Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated
      concentrations of glucose in the blood. The chronic hyperglycemic state accounts
      for most of the vascular complications associated to the disease and the
      prevalent mechanism proposed is related to the glycating chemistry mediated by
      methylglyoxal (MG), which accumulates in T2DM. In recent years, a higher risk of
      Parkinson's disease (PD) onset in people affected by T2DM has become evident, but
      the molecular mechanisms underlying the interplay between T2DM and PD are still
      unknown. The oxidative chemistry of dopamine and its reactivity towards the
      protein alpha-Synuclein (aS) has been associated to the pathogenesis of PD.
      Recently, aS has also been described to interact with MG. Interestingly, MG and
      the dopamine oxidation products share both structural similarity and chemical
      reactivity. The ability of MG to spread over the site of its production and react
      with aS could represent the rationale to explain the higher incidence of PD in
      T2DM-affected people and may open opportunities for the development of novel
      strategies to antagonize the raise of PD.

PMID- 29594937
TI  - Neurobrucellosis Mimicking Neurotuberculosis.

PMID- 29594938
TI  - Urticaria and Anaphylaxis in a Child after Skin Contact of Lentil Soup.

PMID- 29594939
TI  - Dihydropteridine Reductase Deficiency: A Treatable Neurotransmitter Movement
      Disorder Masquerading as Refractory Epilepsy Due to Novel Mutation.

PMID- 29594940
TI  - Effect of Comorbid Psychopathology and Conduct Problem Severity on Response to a
      Multi-component Intervention for Childhood Disruptive Behavior.
AB  - This study examined the effects of comorbid ADHD symptoms, internalizing
      psychopathology, Callous-Unemotional (CU) Traits, and conduct problem severity on
      children's response to an evidence-based psychosocial intervention. Clinic
      referred children with DBD ages 8-12 years (N = 76) participated in a 15-week
      multi-component intervention. Parents provided weekly ratings of children's
      oppositionality-defiance, peer problems, and impairment. Oppositionality
      defiance, peer problems, and impairment decreased significantly over the course
      of the intervention; however, there was considerable variability in weekly
      ratings. Baseline ADHD symptoms, internalizing psychopathology, CU traits, and
      conduct problem severity were unrelated to rate of change across treatment.
      However, ADHD symptoms uniquely predicted more oppositionality-defiance, peer
      problems, and impairment averaged across the 15 weeks of treatment. Follow-up
      analyses suggested this was driven by hyperactivity-impulsivity rather than
      inattention. Children with DBD and comorbid symptoms appear to benefit from a
      multi-component intervention, but those with ADHD symptoms may require additional
      support to address social and behavioral challenges.

PMID- 29594941
TI  - Strategies for Activating Blood Circulation-Regulating Gan (Liver)-Tonifying Shen
      (Kidney) Sequential Therapy of Endometriosis-Associated Infertility.
AB  - Endometriosis (EM) is a major cause of infertility and has a complex
      pathogenesis, which brings severe challenges in both clinical treatment and
      scientific research. Current clinical research focuses on the difficult problem
      of improving the pregnancy rate of EM patients. Our studies found that Chinese
      medicine has significant advantages in terms of improving the pregnancy rate of
      EM patients.

PMID- 29594943
TI  - Bevacizumab improves survival in patients with synchronous colorectal liver
      metastases provided the primary tumor is resected first.
AB  - BACKGROUND: Multimodal strategy including chemotherapy and hepatectomy is
      advocated for the management of colorectal liver metastases (CRLM). The aim of
      this study was to evaluate the impact of neoadjuvant Bevacizumab-based
      chemotherapy on survival in patients with resected stage IVA colorectal cancer
      and liver metastases. METHODS: Data from 120 consecutive patients who received
      neoadjuvant chemotherapy and underwent curative-intent hepatectomy for
      synchronous CRLM were retrospectively reviewed. Overall survival (OS) was
      stratified according to administration of Bevacizumab before liver resection and
      surgical strategy, i.e., classical strategy (primary tumor resection first)
      versus reverse strategy (liver metastases resection first). RESULTS: Patients who
      received Bevacizumab (n = 37; 30%) had a higher number of CRLM (p = 0.003) and
      underwent more often reverse strategy (p = 0.005), as compared to those who did
      not (n = 83; 70%). Bevacizumab was associated with an improved OS compared with
      conventional chemotherapy (p = 0.04). After stratifying by the surgical strategy,
      Bevacizumab was associated with improved OS in patients who had classical
      strategy (p = 0.03). In contrast, Bevacizumab had no impact on OS among patients
      who had liver metastases resection first (p = 0.89). CONCLUSIONS: Neoadjuvant
      Bevacizumab-based chemotherapy was associated with improved OS in patients who
      underwent liver resection of synchronous CRLM, especially in those who underwent
      primary tumor resection first.

PMID- 29594944
TI  - Concurrent use of capecitabine with radiation therapy and survival in breast
      cancer (BC) after neoadjuvant chemotherapy.
AB  - PURPOSE: Capecitabine has been studied as a radiosensitizer, and our study seeks
      to examine the association of concurrent capecitabine/radiation therapy (RT) on
      event-free- (EFS) and overall survival (OS) in women with breast cancer (BC) with
      residual disease after neoadjuvant chemotherapy (NAC). METHODS/PATIENTS: In a
      retrospective study of women with BC who received adriamycin/taxane-based NAC
      from 2004-2016, we identified 21 women administered concurrent capecitabine/RT.
      To assess differences in survival, we selected a clinical control cohort (n = 57)
      based on criteria used to select patients for capecitabine/RT. We also created a
      matched cohort (2:1), matching on tumor subtype, pathological stage and age (< 50
      or 50+ years). Differences in EFS, using STEEP criteria, and OS, using all-cause
      mortality, between those who received capecitabine/RT and controls were assessed.
      RESULTS: Of the 21 women who received capecitabine/RT, median age was 52 years.
      The majority were pathologic stage III (n = 15) and hormone receptor
      positive/HER2-negative BC (n = 20). In those receiving capecitabine/RT, there
      were 9 events, compared with 14 events in clinical and 10 events in matched
      controls. Capecitabine/RT was associated with worse OS in clinical (HR 3.83 95%
      CI 1.12-13.11, p = 0.03) and matched controls (HR 3.71 95% CI 1.04-13.18, p =
      0.04), after adjusting for clinical size, pathological stage and lymphovascular
      invasion. Capecitabine/RT was also associated with a trend towards worse EFS in
      clinical (HR 2.41 95% CI 0.86-6.74, p = 0.09) and matched controls (HR 2.68 95%
      CI 0.91-7.90, p = 0.07) after adjustment. CONCLUSION: Concurrent capecitabine/RT
      after NAC is associated with worse survival and should be carefully considered in
      BC.

PMID- 29594945
TI  - Nur77 suppression facilitates androgen deprivation-induced cell invasion of
      prostate cancer cells mediated by TGF-beta signaling.
AB  - BACKGROUND: Androgen deprivation therapy (ADT) remains a standard treatment for
      advanced prostate cancers. However, recent studies revealed that while inhibiting
      the growth of certain types of prostate cancer cells, ADT promotes invasion. In
      the current study, we explored the effects of Nur77, an orphan nuclear receptor,
      on prostate cancer cell invasion following ADT. METHODS: Androgen receptor (AR)
      and Nur77 protein expression in patient tissues and cell lines were quantified
      via ELISA and western blot. The effects of AR-signaling on Nur77 expression were
      examined. The effects of Nur77 over-expression and knockdown on ADT-induced
      prostate cancer cell invasion were characterized. RESULTS: The results showed
      that AR and Nur77 are both highly expressed in prostate cancers of patients.
      Nur77 is positively regulated by AR-signaling at transcriptional level in NCI
      H660, a widely used prostate cancer cell line. AR antagonists, Casodex and
      MDV3100 treatment resulted in significant inhibition of prostate cancer cell
      growth but enhanced cancer cell invasion. Nur77 over-expression blocked invasion
      promoting effect of ADT, which is consistent with the down-regulation of MMP9 and
      Snail protein expression. Further mechanistic investigations showed that Nur77
      inhibited transcription of TGF-beta target genes (Snail and MMP9), and thereby
      inhibits TGF-beta-mediated prostate cancer cell invasion following androgen
      antagonism. In addition, our data suggested the nature of this inhibitory effect
      of Nur77 on TGF-beta-signaling is selective, for Smad3-signaling, the classical
      effector of TGF-beta-signaling, was not interrupted by Nur77 over-expression.
      CONCLUSION: Considering the limited success of management of prostate cancer
      metastasis following ADT, our data strongly suggest that Nur77 regulation could
      be a promising direction for search of complementary therapeutic strategy on top
      of classic ADT therapy.

PMID- 29594946
TI  - Mitochondria-Mediated Pathway Regulates C2C12 Cell Apoptosis Induced by Fluoride.
AB  - This study was designed to investigate the mechanisms of excessive fluoride
      induced apoptosis via mitochondria-mediated pathway in skeletal muscle cells
      (C2C12 cells). C2C12 cells were cultured with the fluoride concentrations (0, 1,
      and 2.5 mmol/L) for 48 h. The morphology and ultrastructural changes of C2C12
      cells were observed using a light microscope and transmission electron microscope
      (TEM). The protein expression levels of apoptosis factors, including Bax, Bcl-2,
      cytochrome c (Cyt c), caspase-3, and caspase-9, were measured using real-time
      polymerase chain reaction (real-time PCR) and immunocytofluorescence. The
      morphology and ultrastructure of C2C12 cells were seriously damaged by fluoride
      at 1 and 2.5 mmol/L doses, including swollen mitochondria, vacuolization, ridge
      breakage, and disappearance of the nuclear membrane. Simultaneously, compared
      with the control group, the expression levels of Bax, Bcl-2, Cyt c, caspase-3,
      and caspase-9 were up-regulated after fluoride treatment. Excessive fluoride
      damages the ultrastructure in mitochondria, leading to the release of Cyt c from
      the mitochondria to cytoplasm in C2C12 cells; thereby, activated caspases cascade
      apoptosis process through a mitochondria-mediated pathway.

PMID- 29594947
TI  - A Neuro-Comparative Study between Single/Successive Thorium Dose Intoxication and
      Alginate Treatment.
AB  - The adult male albino rats were grouped into five groups (control group and four
      variably treated groups with thorium (Th) in single or successive with or without
      alginate treatment). The IP administration of thorium nitrate (13.6 mg/kg b.wt.)
      induced a regional distribution and accumulation ordered as cerebellum > cerebral
      cortex > brain stem > hippocampus > hypothalamus > striatum. Also, it induces a
      significant increase in Na+, Ca2+, and Fe3+ ion content and malondialdehyde (MDA)
      level while K+ ions and glutathione (GSH) level were significantly decreased. On
      the other hand, the daily oral administration of 5% alginate showed a significant
      decreasing in the accumulation of thorium in the different brain areas and
      mitigated its hazardous effects. By the alginate treatment, Na+, Ca2+, Fe3+, and
      level of MDA were declined while K+ ions and GSH level showed a significant
      increase. The improvement of the investigated parameters was attributed to the
      specific chelating, regeneration, and antioxidant properties of the alginate. So,
      alginate administration could ameliorate the hazardous effects of thorium
      nitrate.

PMID- 29594948
TI  - Effect of Lead on Antioxidant Ability and Immune Responses of Crucian Carp.
AB  - The aim of this study was to explore the effects of lead exposure on the
      antioxidant and immune responses of Crucian carp. Three hundred sixty healthy
      Crucian carp were randomly grouped into four groups and exposed to different
      doses of lead (0, 0.05, 0.5, and 1 mg/L). Fish were sampled at 30 and 60 days,
      respectively, and antioxidant capability, immune parameters, ALAD activity, and
      immune-related genes were assessed. The results showed that T-AOC and GSH
      activities of the liver were significantly increased in 60 days (P < 0.05); the
      activities of SOD, CAT, T-AOC, and GSH were significantly increased (P < 0.05)
      compared to the control in the kidney in 60 days. With an increase in Pb dose,
      the activity and expression of lysozyme and the content of immunoglobulin M were
      significantly decreased compared to the control. Compared with the control group,
      the activity of ALAD in the lead-exposed group decreased significantly (P <
      0.05). The expression of the HSP70, tumor necrosis factor-alpha (TNF-alpha),
      interleukins (IL-10), and immunoglobulin M genes was all enhanced in lead-exposed
      group, whereas lysozyme gene expression was decreased. The results indicated that
      lead induced oxidative stress and had immunotoxic effects on Crucian carp.

PMID- 29594942
TI  - The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging
      Pathophysiological Role and Translational Implications.
AB  - The endoplasmic reticulum (ER) is the main cellular organelle involved in protein
      synthesis, assembly and secretion. Accumulating evidence shows that across
      several neurodegenerative and neuroprogressive diseases, ER stress ensues, which
      is accompanied by over-activation of the unfolded protein response (UPR).
      Although the UPR could initially serve adaptive purposes in conditions associated
      with higher cellular demands and after exposure to a range of pathophysiological
      insults, over time the UPR may become detrimental, thus contributing to
      neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative,
      neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact
      with aberrations in UPR pathways. Furthermore, ER stress may contribute to a
      deregulation in calcium homoeostasis. The common denominator of these pathways is
      a decrease in neuronal resilience, synaptic dysfunction and even cell death. This
      review also discusses how mechanisms related to ER stress could be explored as a
      source for novel therapeutic targets for neurodegenerative and neuroprogressive
      diseases. The design of randomised controlled trials testing compounds that
      target aberrant UPR-related pathways within the emerging framework of precision
      psychiatry is warranted.

PMID- 29594949
TI  - Characterization of multiple antibiotic resistant clinical strains of
      Staphylococcus isolated from pregnant women vagina.
AB  - Vagina which is one of the important reservoirs for Staphylococcus and in
      pregnant women pathogenic strains may infect the child during the birth or by
      vertical transmission. A total of 68 presumptive Staphylococcus strains isolated
      from human vagina were found to be gram-positive cocci, and only 32 (47%)
      isolates were found beta-hemolytic. Matrix-assisted laser desorption/ionization
      time-of-flight mass-spectrometry (MALDI-TOF MS) results confirmed 33 isolates
      belonged to Staphylococcus which consisting of 6 species, i.e., S. aureus (14),
      S. vitulinus (7), S. epidermidis (4), S cohnii (3), S. equorum (3), and S.
      succinus (2). Further, the result of antibiotic susceptibility tests showed that
      large proportions (76%-100%) of the isolates were resistant to multiple
      antibiotics and more often resistant to penicillin (100%), ampicillin (100%),
      oxacillin (97%), oxytetracycline (97%), vancomycin (97%), rifampin (85%),
      erythromycin (82%), and streptomycin (76%). In the present study, only the sec
      enterotoxin gene was detected in four S. aureus strains. DNA fingerprints of the
      33 isolates that were generated using random amplified polymorphic DNA (RAPD) and
      enterobacterial repetitive intergenic consensus (ERIC) PCR analysis revealed
      great genetic relatedness of isolates. High prevalence of vaginal colonization
      with multiple antibiotic-resistant staphylococci among pregnant women was
      observed which were emerged from the single respective species clones that
      underwent evolution. The vertical transmission of these multiple antibiotic
      resistant Staphylococcus species to the infant is possible; therefore, the
      findings of this study emphasize the need for regular surveillance of antibiotic
      resistant bacterial strains in pregnant women in this area.

PMID- 29594951
TI  - Obinutuzumab with Bendamustine for Treating Follicular Lymphoma Refractory to
      Rituximab: An Evidence Review Group Perspective of a NICE Single Technology
      Appraisal.
AB  - As part of its single technology appraisal process, the UK National Institute for
      Health and Care Excellence (NICE) invited the manufacturer of obinutuzumab
      (Roche) to submit evidence on its clinical and cost effectiveness when used in
      combination with bendamustine in patients with follicular lymphoma (FL)
      refractory to rituximab. The Evidence Review Group (ERG), the School of Health
      and Related Research Technology Appraisal Group at the University of Sheffield,
      produced a document summarising the key points from the company submission
      alongside a critical review. Efficacy for progression-free survival (PFS) and
      safety was positively demonstrated in the pivotal GADOLIN trial, which compared
      obinutuzumab in combination with bendamustine followed by obinutuzumab
      maintenance (O-Benda+O) against bendamustine monotherapy. Data on overall
      survival were immature. The company submitted a model-based economic analysis,
      including a patient access scheme. The ERG identified a number of limitations, in
      particular the absence of subgroup analysis and the approach used by the company
      to estimate overall survival (OS), which was more favourable to the intervention
      arm. The key uncertainty was the duration of the treatment effect on OS. This
      uncertainty is expected to be reduced when the final analysis of the GADOLIN
      trial is reported. Consequently, the NICE appraisal committee recommended O
      Benda+O in the population covered by the marketing authorisation within the
      Cancer Drug Fund until NICE is able to review the guidance following publication
      of the final analysis of GADOLIN.

PMID- 29594950
TI  - The effect of human sperm chromatin maturity on ICSI outcomes.
AB  - Because sperm chromatin may play a key role in reproductive success, we verify
      the associations between sperm chromatin abnormalities, embryo development and
      the ability to achieve pregnancy. The evaluation of sperm chromatin maturity
      using aniline blue (AB), chromomycin A3 (CMA3) and toluidine blue (TB) staining
      were carried out in group of males from infertile couples that underwent ICSI.
      Low levels of sperm chromatin abnormalities (< 16%) were found in most subjects
      (> 50%). A higher percentage of TB-positive sperm cells were discovered in the
      men from couples who achieved <= 50% fertilized oocytes compared to men who
      achieved > 50%. No significant differences were discovered by the applied tests
      between the men from couples who achieved <= 50% and those who achieved > 50%
      high-quality embryos on the 3rd or 5th day after fertilization, nor between the
      men from couples who achieved pregnancy and those who failed. The sperm chromatin
      maturity did not correlate with the ICSI results. However, the ROC analysis
      revealed a significant predictive value of TB-positive spermatozoa only for
      fertilization. Therefore, the TB assay can be considered as a useful test for the
      prediction of fertilization. Our findings suggest that the level of sperm
      chromatin abnormalities of the examined men was not clinically significant. No
      found associations between sperm chromatin maturity and embryo development and
      the ability to achieve pregnancy. We could not exclude the effects of the
      repairing processes in the fertilized oocyte. The use of complementary tests that
      verify the status of the sperm chromatin seems justified.

PMID- 29594954
TI  - Irpexoates A-D, Four Triterpenoids with Malonyl Modifications from the Fruiting
      Bodies of the Medicinal Fungus Irpex lacteus.
AB  - Four eburicane-type triterpenoids with malonyl modifications, namely irpexoates A
      D (1-4), were isolated from the fruiting bodies of the medicinal fungus Irpex
      lacteus. The structures of the new compounds were established by extensive
      spectroscopic methods, including 1D and 2D NMR, HRESIMS spectroscopic analysis.
      Irpexoate B (2) displayed weak cytotoxicity against four human cancer cell lines
      (A-549, SMMC-7721, MCF-7, SW480) with IC50 values varying from 22.9 to 34.0 MUM,
      and irpexoate D (4) showed weak cytotoxicity against the human cancer cell line
      SW480 with an IC50 value of 35.2 MUM.

PMID- 29594955
TI  - Familial Hypercholesterolemia: Nip the Evil in the Bud.

PMID- 29594952
TI  - Absolute quantification of selected photosynthetic electron transfer proteins in
      Chlamydomonas reinhardtii in the presence and absence of oxygen.
AB  - The absolute amount of plastocyanin (PC), ferredoxin-NADP+-oxidoreductase (FNR),
      hydrogenase (HYDA1), and ferredoxin 5 (FDX5) were quantified in aerobic and
      anaerobic Chlamydomonas reinhardtii whole cells using purified (recombinant)
      proteins as internal standards in a mass spectrometric approach. Quantified
      protein amounts were related to the estimated amount of PSI. The ratios of PC to
      FNR to HYDA1 to FDX5 in aerobic cells were determined to be 1.4:1.2:0.003:0. In
      anaerobic cells, the ratios changed to 1.1:1.3:0.019:0.027 (PC:FNR:HYDA1:FDX5).
      Employing sodium dithionite and methyl viologen as electron donors, the specific
      activity of hydrogenase in whole cells was calculated to be 382 +/- 96.5 MUmolH2
      min-1 mg-1. Importantly, these data reveal an about 70-fold lower abundance of
      HYDA1 compared to FNR. Despite this great disproportion between both proteins,
      which might further enhance the competition for electrons, the alga is capable of
      hydrogen production under anaerobic conditions, thus pointing to an efficient
      channeling mechanism of electrons from FDX1 to the HYDA1.

PMID- 29594953
TI  - Ceftolozane/tazobactam for the treatment of XDR Pseudomonas aeruginosa
      infections.
AB  - PURPOSE: The aim of this study was to evaluate the effectiveness of
      ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas
      aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g
      ceftolozane and 1 g tazobactam every 8 h) and infection source control have an
      impact on outcome. METHODS: Retrospective study of all consecutive patients
      treated with C/T for XDR-PA infection at a tertiary referral hospital (November
      2015-July 2017). Main clinical and microbiological variables were analyzed.
      RESULTS: Thirty-eight patients were included. Median age was 59.5 years and
      Charlson Comorbidity Index was 3.5. Fourteen (36.8%) patients had respiratory
      tract infection, six (15.8%) soft tissue, and six (15.8%) urinary tract
      infection. Twenty-three (60.5%) received high-dose C/T and in 24 (63.2%) C/T was
      combined with other antibiotics. At completion of treatment, 33 (86.8%) patients
      showed clinical response. At 90 days of follow-up, 26 (68.4%) achieved clinical
      cure, and 12 (31.6%) had clinical failure because of persistent infection in one
      patient, death attributable to the XDR-PA infection in four, and clinical
      recurrence in seven. All-cause mortality was 5 (13.2%). Lower C/T MIC and
      adequate infection source control were the only variables significantly
      associated with clinical cure. CONCLUSIONS: C/T should be considered for treating
      XDR-PA infections, with infection source control being an important factor to
      avoid failure and resistance.

PMID- 29594956
TI  - Mechanisms and Effects on HBV Replication of the Interaction between HBV Core
      Protein and Cellular Filamin B.
AB  - Hepatitis B virus (HBV) infection is one of the major problems that threatens
      global health. There have been many studies on HBV, but the relationship between
      HBV and host factors is largely unexplored and more studies are needed to clarify
      these interactions. Filamin B is an actin-binding protein that acts as a
      cytoskeleton protein, and it is involved in cell development and several
      signaling pathways. In this study, we showed that filamin B interacted with HBV
      core protein, and the interaction promoted HBV replication. The interaction
      between filamin B and core protein was observed in HEK 293T, Huh7 and HepG2 cell
      lines by co-immunoprecipitation and co-localization immnofluoresence.
      Overexpression of filamin B increased the levels of HBV total RNAs and pre-genome
      RNA (pgRNA), and improved the secretion level of hepatitis B surface antigen
      (HBsAg) and hepatitis B e antigen (HBeAg). In contrast, filamin B knockdown
      inhibited HBV replication, decreased the level of HBV total RNAs and pgRNA, and
      reduced the secretion level of HBsAg and HBeAg. In addition, we found that
      filamin B and core protein may interact with each other via four blocks of
      argentine residues at the C-terminus of core protein. In conclusion, we identify
      filamin B as a novel host factor that can interact with core protein to promote
      HBV replication in hepatocytes. Our study provides new insights into the
      relationship between HBV and host factors and may provide new strategies for the
      treatment of HBV infection.

PMID- 29594957
TI  - Exhaustive Exercise Does Not Affect Humoral Immunity and Protection after Rabies
      Vaccination in a Mouse Model.
AB  - Rabies is one of the most dangerous and widespread zoonosis and is characterized
      by severe neurological signs and a high case-mortality rate of nearly 100%.
      Vaccination is the most effective way to prevent rabies in humans and animals. In
      this study, the relationship between exhaustive exercise and the humoral immune
      response after immunization with inactivated rabies vaccine was investigated in a
      mouse model with one-time exhaustive exercise. It was found that compared with
      the mice with no exercise after vaccination, no significant differences were
      found in those with exhaustive exercise after vaccination on body-weight changes,
      virus-neutralizing antibody (VNA) titers, antibody subtypes and survivor ratio
      after lethal rabies virus (RABV) challenge. This study indicated that exhaustive
      exercise does not reduce the effects of the rabies inactivated vaccine.

PMID- 29594958
TI  - Change of Direction Speed: Toward a Strength Training Approach with Accentuated
      Eccentric Muscle Actions.
AB  - There is growing evidence that eccentric strength training appears to have
      benefits over traditional strength training (i.e., strength training with
      combined concentric and eccentric muscle actions) from muscular, neuromuscular,
      tendinous, and metabolic perspectives. Eccentric muscle strength is particularly
      needed to decelerate and stabilize the body during the braking phase of a jump
      exercise or during rapid changes of direction (CoD) tasks. However, surprisingly
      little research has been conducted to elucidate the effects of eccentric strength
      training or strength training with accentuated eccentric muscle actions on CoD
      speed performance. In this current opinion article, we present findings from
      cross-sectional studies on the relationship between measures of eccentric muscle
      strength and CoD speed performance. In addition, we summarize the few available
      studies on the effects of strength training with accentuated eccentric muscle
      actions on CoD speed performance in athletic populations. Finally, we propose
      strength training with accentuated eccentric muscle actions as a promising
      element in strength and conditioning programs of sports with high CoD speed
      demands. Our findings from five cross-sectional studies revealed statistically
      significant moderate- to large-sized correlations (r = 0.45-0.89) between
      measures of eccentric muscle strength and CoD speed performance in athletic
      populations. The identified three intervention studies were of limited
      methodological quality and reported small- to large-sized effects (d = 0.46-1.31)
      of strength training with accentuated eccentric muscle actions on CoD speed
      performance in athletes. With reference to the available but preliminary
      literature and from a performance-related point of view, we recommend strength
      and conditioning coaches to include strength training with accentuated eccentric
      muscle actions in training routines of sports with high CoD speed demands (e.g.,
      soccer, handball, basketball, hockey) to enhance sport-specific performance.
      Future comparative studies are needed to deepen our knowledge of the effects of
      strength training with accentuated eccentric muscle actions on CoD speed
      performance in athletes.

PMID- 29594959
TI  - Author's Reply to Andreato et al.: Comment on: "Effect of High-Intensity Interval
      Training on Total, Abdominal and Visceral Fat Mass: A Meta-Analysis".

PMID- 29594960
TI  - Comment on: "Effect of High-Intensity Interval Training on Total, Abdominal and
      Visceral Fat Mass: A Meta-Analysis".

PMID- 29594961
TI  - Comparative performance of dairy cows in low-input smallholder and high-input
      production systems in South Africa.
AB  - The aim of this study was to benchmark the performance of dairy cows in the low
      input smallholder system against their counterparts in the high-input system, in
      South Africa. Data comprised of cow performance records from the national dairy
      recording scheme. Performance measures included production (305-day yields of
      milk, fat, and protein), lactation length, somatic cell count (SCC), and
      reproductive traits, represented by age at first calving (AFC) and calving
      interval (CI). Least squares means of each trait were compared between the two
      systems, and lactation curves for production traits and SCC were plotted for each
      production system. Mean yields of milk, fat, and protein were significantly (P <
      0.05) lower in the smallholder (4097 +/- 165, 174 +/- 5.1, and 141 +/- 4.5
      respectively) compared to the high-input system (6921 +/- 141, 298 +/- 4.7, and
      245 +/- 4.1 respectively). Mean lactation length was significantly (P < 0.05)
      shorter for the smallholder (308 +/- 15.1) than the high-input system (346 +/-
      12.8). Log-transformed somatic cell count (SCS) was, however, significantly (P <
      0.05) higher in the smallholder (2.41 +/- 0.01) relative to the high-input system
      (2.27 +/- 0.01). Cows in high-input herds showed typical lactation curves, in
      contrast to the flat and low peaking curves obtained for the smallholder system.
      Cows on smallholder herds had their first calving significantly (P < 0.05) older
      (30 +/- 0.5) than those in the high-input system (27 +/- 0.5). There was,
      however, no significant difference (P < 0.05) in CI between the two systems.
      These results highlight large room for improvement of dairy cow performance in
      the smallholder system and could assist in decision-making aimed at improving the
      productivity of the South African dairy industry.

PMID- 29594962
TI  - Influence of distance to urban markets on smallholder dairy farming systems in
      Kenya.
AB  - We studied influence of distance to urban markets on smallholder dairy farming
      system development. Farms were chosen from three locations that varied in
      distance to the urban market of Nakuru Town in the Kenyan highlands: urban
      location (UL, n = 10) at less than 15 km distance, mid-rural location (MRL, n =
      11) in between 20 and 50 km west of Nakuru and extreme rural location (ERL, n =
      9) beyond 50 km west and south-west of Nakuru. In-depth interviews with farmers
      and focus group discussions with eight groups of stakeholders were held to
      collect narratives and data about market quality, production factors, farm
      performance and functions of dairy cattle. We applied thematic content analysis
      to qualitative information by clustering narratives according to predefined
      themes and used ANOVA to analyse farm data. In UL, markets were functional, with
      predominantly informal market chains, with a high milk price (US $ 45.1/100 kg).
      Inputs were available in UL markets, but prices were high for inputs such as
      concentrates, fodder, replacement stock and hired labour. Moreover, availability
      of grazing land and the high opportunity costs for family labour were limiting
      dairy activities. In UL, milk production per cow (6.9 kg/cow/day) and per farm
      (20.1 kg/farm/day) were relatively low, and we concluded that farm development
      was constrained by scarcity of inputs and production factors. In rural locations
      (MRL and ERL), markets were functional with relatively low prices (average US $
      32.8/100 kg) for milk in both formal and informal market chains. Here,
      concentrates were relatively cheap but also of low quality. Fodder, replacement
      stock and labour were more available in rural locations than in UL. In rural
      locations, milk production per cow (average 7.2 kg/cow/day) and per farm (average
      18.5 kg/farm/day) were low, and we concluded that farm development was
      constrained by low quality of concentrates and low price of milk. In all
      locations, production for subsistence was valued since income generated was used
      for non-dairy expenses. A tailor-made package of interventions that targets the
      above constraints is recommended for farm development.

PMID- 29594963
TI  - The effects of PPR on the reproductive health of Black Bengal goats and the
      possible role played by oxidative stress.
AB  - Outbreaks of Peste des petits ruminants (PPR) viral disease in Black Bengal goats
      were investigated from the middle Indo-Gangetic Plains of India. Clinical profile
      of PPR-affected flocks was recorded from four different outbreak sites of the
      region. The PPR outbreak was diagnosed serologically using commercially available
      sandwich ELISA kit. Relatively, low mortality rate (mean 26.75%) for PPR outbreak
      was recorded due to the endemic status of the disease. To understand the role of
      oxidative stress in PPR virus pathogenesis, various oxidant and antioxidant
      parameters in goats infected with PPR were estimated and compared with the
      uninfected/healthy goats of the same flock. The measured high level of pro
      oxidant malondialdehyde (MDA) obtained from lipid peroxidation along with lower
      levels of anti-oxidants viz. superoxide dismutase (SOD), glutathione peroxidase
      (GPx) and catalase (CAT) in PPR-affected Black Bengal goats suggests oxidative
      stress as one of the mechanism of pathogenesis of PPR virus. In addition, the
      correlation of oxidative stress due to PPR and the resulting reproductive
      disorders in the female goats were evaluated. The abortion in pregnant does
      observed during PPR outbreak was proportional to debility and oxidative stress
      manifested during PPR infection. The reproductive performance of recovered female
      goats in the period of 18 months of monitoring was significantly compromised in
      terms of kidding and twinning frequency. The mortality rate in kids born from PPR
      recovered goats was significantly higher compared to those from health goats in
      the first 9 months post-recovery. From the present study, it may be concluded
      that together with the PPR virus, infection in goats and the resulting oxidative
      stress play a vital role for abortion and reduced post-reproductive performance
      in Black Bengal female goat.

PMID- 29594965
TI  - Quality of life in patients with MuSK positive myasthenia gravis.
AB  - It is believed that myasthenia gravis (MG) with antibodies to muscle-specific
      tyrosine kinase (MuSK) is the most severe form of the disease, especially in the
      first years of the disease. The aim of our study was to investigate quality of
      life (QoL) in a population of patients with MuSK MG compared to those with MG who
      have antibodies to acetylcholine receptor (AChR) in their sera. The study group
      consisted of 35 MuSK MG patients (28 females and 7 males), while the control
      group included 38 AChR MG patients matched for gender, age, and duration of the
      disease. SF-36 questionnaire was used to evaluate the health-related QoL.
      Following scales were also used: Hamilton's scales for depression and anxiety,
      the Multidimensional Scale of Perceived Social Support, and the Acceptance of
      Illness Scale. Physical domain scores of QoL were similarly affected in both MuSK
      and AChR groups, while mental domain and total SF-36 scores were even better in
      MuSK MG patients. Social support was better in the MuSK group (77.3 +/- 9.3 vs.
      70.6 +/- 14.1, p < 0.05). SF-36 total score correlated with depression (rho =
      0.54, p < 0.01), anxiety (rho = 0.49, p < 0.01), and MSPSS (rho = - 0.35, p <
      0.05), and depression was an independent predictor of worse QoL. Besides therapy
      of weakness, psychiatric treatment and different forms of psychosocial condition
      should be part of regular therapeutic protocols for MG. Adequate team work of
      health professionals and family can provide a healthy mental environment in which
      a MuSK MG patient would feel more comfortable in spite of the disease.

PMID- 29594966
TI  - T cell receptor-beta J usage, in combination with particular HLA class II
      alleles, correlates with better cancer survival rates.
AB  - T cell receptor (TCR) beta V and J usage correlates with either the HLA class I
      or HLA class II major histocompatibility subtypes, and in both infectious
      diseases and autoimmune settings, the use of particular TCR-beta V and J's, in
      persons with specific HLA alleles, represents either better outcomes or certain
      clinical features. However, the relationship of TCR V and J usage, HLA alleles,
      and clinical parameters in the cancer setting has been less well studied. Here,
      we have evaluated the relationship of what is likely dominant TCR-beta V and J
      usage among tissue-resident lymphocytes for lung, head and neck, kidney, stomach,
      ovarian, and endometrial cancers, with patient HLA class II alleles. The most
      striking indication is that TCR-beta J subgroup usage, in combination with
      particular patient HLA class II alleles, correlated with either better or worse
      outcomes for lung cancer. One combination, TCR-beta J2 segment usage and the HLA
      DRB1*1501 allele, correlated with a better survival rate for both lung and head
      and neck cancers. These results fill a gap in knowledge regarding the relevance
      of HLA typing to cancer and indicate that HLA typing, along with an indication of
      dominant TCR-beta J usage among tissue-resident lymphocytes, can be useful for
      prognosis.

PMID- 29594964
TI  - CVIT expert consensus document on primary percutaneous coronary intervention
      (PCI) for acute myocardial infarction (AMI) in 2018.
AB  - While primary percutaneous coronary intervention (PCI) has significantly
      contributed to improve the mortality in patients with ST segment elevation
      myocardial infarction even in cardiogenic shock, primary PCI is a standard of
      care in most of Japanese institutions. Whereas there are high numbers of
      available facilities providing primary PCI in Japan, there are no clear
      guidelines focusing on procedural aspect of the standardized care. Whilst updated
      guidelines for the management of acute myocardial infarction were recently
      published by European Society of Cardiology, the following major changes are
      indicated; (1) radial access and drug-eluting stent over bare metal stent were
      recommended as Class I indication, and (2) complete revascularization before
      hospital discharge (either immediate or staged) is now considered as Class IIa
      recommendation. Although the primary PCI is consistently recommended in recent
      and previous guidelines, the device lag from Europe, the frequent usage of
      coronary imaging modalities in Japan, and the difference in available medical
      therapy or mechanical support may prevent direct application of European
      guidelines to Japanese population. The Task Force on Primary Percutaneous
      Coronary Intervention of the Japanese Association of Cardiovascular Intervention
      and Therapeutics (CVIT) has now proposed the expert consensus document for the
      management of acute myocardial infarction focusing on procedural aspect of
      primary PCI.

PMID- 29594967
TI  - Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and
      Clostridium difficile.
AB  - BACKGROUND/OBJECTIVES: Patients colonized with toxinogenic strains of Clostridium
      difficile have an increased risk of subsequent infection. Given the potential
      role of the gut microbiome in increasing the risk of C. difficile colonization,
      we assessed the diversity and composition of the gut microbiota among long-term
      care facility (LTCF) residents with advanced dementia colonized with C.
      difficile. DESIGN: Retrospective analysis of rectal samples collected during a
      prospective observational study. SETTING: Thirty-five nursing homes in Boston,
      Massachusetts. PARTICIPANTS: Eighty-seven LTCF residents with advanced dementia.
      MEASUREMENTS: Operational taxonomic units were identified using 16S rRNA
      sequencing. Samples positive for C. difficile were matched to negative controls
      in a 1:3 ratio and assessed for differences in alpha diversity, beta diversity,
      and differentially abundant features. RESULTS: Clostridium difficile sequence
      variants were identified among 7/87 (8.04%) residents. No patient had evidence of
      C. difficile infection. Demographic characteristics and antimicrobial exposure
      were similar between the seven cases and 21 controls. The overall biodiversity
      among cases and controls was reduced with a median Shannon index of 3.2
      (interquartile range 2.7-3.9), with no statistically significant differences
      between groups. The bacterial community structure was significantly different
      among residents with C. difficile colonization versus those without and included
      a predominance of Akkermansia spp., Dermabacter spp., Romboutsia spp.,
      Meiothermus spp., Peptoclostridium spp., and Ruminococcaceae UGC 009. CONCLUSION:
      LTCF residents with advanced dementia have substantial dysbiosis of their gut
      microbiome. Specific taxa characterized C. difficile colonization status.

PMID- 29594968
TI  - Profiles of Patients Who Use Marijuana for Inflammatory Bowel Disease.
AB  - BACKGROUND: Marijuana is legal in a number of states for indications that include
      inflammatory bowel diseases (IBD), and patients are interested in its potential
      benefits. AIMS: We aimed to describe the legal use of marijuana in individuals
      with IBD in the USA who participate within the CCFA Partners internet-based
      cohort. METHODS: A total of 2357 participants who lived in states where
      prescription or recreational marijuana was legal, were offered the opportunity to
      complete a survey on marijuana use and IBD symptoms including perceived benefits
      of therapy. Bivariate statistics and logistic regression models were used to
      determine factors associated with marijuana use. RESULTS: Surveys were completed
      by 1666 participants (71%) with only 214 (12.8%) indicating they had asked their
      medical doctor about its use and 73 actually using prescribed marijuana (4.4%).
      Within the respondent group (N = 1666), 234 participants lived where both medical
      and recreational marijuana is legal and 49 (20.9%) reported recreational
      marijuana use specifically for IBD. Users reported positive benefits (80.7%), but
      users also reported more depression, anxiety, pain interference, and lower social
      satisfaction than non-users. Those prescribed marijuana reported more active
      disease, and more use of steroids, narcotics, and zolpidem. CONCLUSIONS: Few IBD
      patients consulted their medical doctors about marijuana use or used prescription
      marijuana. Where recreational marijuana was available, usage rates were higher.
      Users reported benefits but also more IBD symptoms, depression, anxiety, and
      pain. Marijuana use may be higher in patients with IBD symptoms not well treated
      by conventional medical approaches.

PMID- 29594969
TI  - Hepatic Encephalopathy and Helicobacter pylori.

PMID- 29594970
TI  - Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory
      Bowel Disease Patients.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) are often
      immunosuppressed, and those patients receiving anti-tumor necrosis factor alpha
      (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are
      at their highest levels in the post-vaccine era. There is little data regarding
      responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in
      IBD patients. AIMS: The aim of this study was to compare sustained vaccine
      induced Tdap antibody concentrations in a cohort of IBD patients stratified by
      medication regimens with healthy controls (HC) who had received an adult Tdap
      booster. METHODS: We performed a cross-sectional study evaluating antibody
      responses to Tdap vaccine among IBD patients compared to HC. Our study consisted
      of three patient groups: adults with IBD stratified by maintenance medication
      regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3)
      combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)).
      RESULTS: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody
      concentrations were significantly lower in IBD patients (p = 0.021) compared to
      HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody
      concentrations compared to those on thiopurine monotherapy (p = 0.028).
      Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001),
      and those on anti-TNF agents (monotherapy or combination) had lower antibody
      concentrations compared to the thiopurine monotherapy group (p < 0.001).
      CONCLUSION: IBD patients on anti-TNF agents had lower antibody concentrations to
      diphtheria and pertussis. These findings suggest a need for different Tdap
      booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry
      NCT02434133.

PMID- 29594971
TI  - Association between malocclusion and dental caries in adolescents: a systematic
      review and meta-analysis.
AB  - AIM: To evaluate the scientific evidence regarding the association between
      malocclusion and dental caries in adolescents. METHODS: Searches were conducted
      of six electronic databases, complemented by manual searching of the reference
      lists of the selected articles and grey literature. Two independent reviewers
      performed the selection of the articles, data extraction and the evaluation of
      the risks of bias through an assessment of methodological quality. Meta-analysis
      was performed considering the mean decayed, missing and filled teeth (DMFT) index
      for caries and the Dental Aesthetic Index (DAI) for malocclusion. Heterogeneity
      was tested using the I2 statistic and a random effect model was employed. Summary
      effect measures were calculated as differences in means. RESULTS: The initial
      search retrieved 2644 studies, only 15 of which were selected for full-text
      analysis. Four cross-sectional studies were included in the qualitative
      systematic review. Only one of these studies found no association between
      malocclusion and dental caries. The meta-analysis of three studies demonstrated
      that a lower DAI value was significantly associated with a lower mean DMFT index,
      except for the comparison of DAI 26-30 vs. 31-35. CONCLUSIONS: Based on the
      studies analysed, the scientific evidence indicates an association between
      malocclusion and dental caries.

PMID- 29594973
TI  - Clinical and Therapeutic Aspects of Linear Psoriasis: A Study of 30 Cases.
AB  - BACKGROUND: Psoriasis affects 2-4% of the population, with the most common
      clinical type being plaque psoriasis. The linear form of psoriasis is very rare.
      The literature on linear psoriasis (LP) consists of only case reports, and data
      are few. OBJECTIVE: This study aimed to better understand LP in a large-scale
      study. PATIENTS AND METHODS: We retrospectively retrieved the medical records
      from 14 French medical centers of patients newly diagnosed clinically with LP,
      with or without the support of histology, between 1 February and 31 July 2015.
      For each case, we assessed the clinical features, treatments and treatment
      efficacy. RESULTS: In total, 30 cases of LP (mean age 26.8 years, 13 males) were
      reported. Mean age at onset of LP was 20.0 years, with 18 developing LP in
      childhood. Ten patients had a family history of psoriasis, and two had psoriatic
      arthritis. A total of 19 cases were linear at onset, with concomitant classical
      psoriasis; these were termed "superimposed" LP. The remaining 11 cases were not
      associated with classical psoriasis and were termed "isolated" LP. In four of the
      superimposed cases, LP developed when the patient was receiving systemic
      treatment: methotrexate (n = 2), etanercept (n = 1) or infliximab (n = 1).
      Topical steroids were effective in 76% of cases in which they were used, and
      systemic treatment was effective in < 66%. Treatments were less effective in LP
      than in classical psoriasis. DISCUSSION: We identified a wide range of LP, with
      two profiles: isolated LP and superimposed LP. Topical treatment usually evoked
      clinical response, with relative resistance to systemic therapy. Methotrexate and
      anti-tumor necrosis factor (TNF)-alpha therapies can possibly unmask LP.

PMID- 29594972
TI  - A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance
      and Hyperalgesia: A Review.
AB  - Chronic pain is an important health and social problem. Misuse and abuse of
      opioids in chronic non-cancer pain management seem to be a huge problem, in some
      countries. This could probably affect the normal use of such analgesics in
      patients in need of them. Basic and clinical researches should find the solution
      to mitigate the potential damage. Dysregulation of mast cell and microglia
      activation plays an important role in the pathogenesis and management of chronic
      pain. Persistent mast cell activation sensitizes nociceptors and initiates
      central nervous system inflammatory processes, involving microglial cell
      activation and sensitization of spinal somatosensory neurons. Exposure of mast
      cells and microglia to opioids is well known to provoke activation of these non
      neuronal immune cell populations, thereby contributing to an exacerbation of pro
      inflammatory and pro-nociceptive processes and promoting, over the long-term,
      opioid-induced hyperalgesia and tolerance. This review is intended to provide the
      reader with an overview of the role for these non-neuronal cells in opioid
      induced chronic pain and tolerance as a consequence of prolonged exposure to
      these drugs. In addition, we will examine a potential strategy with the aim to
      modulate opioid-induced over-activation of glia and mast cells, based on
      endogenous defense mechanisms and fatty acid amide signaling molecules.

PMID- 29594974
TI  - Emerging Therapies for Acne Vulgaris.
AB  - As we gain a greater understanding of acne pathogenesis, both new agents as well
      as new uses for established drugs are being considered for the treatment of acne
      vulgaris. Multiple clinical trials assessing new formulations or combinations of
      established acne treatments have been conducted, and novel uses of antimicrobials
      such as modified diallyl disulfide oxide and nitric oxide are being assessed in
      clinical trials. There are also a multitude of new therapies currently being
      studied that target the inflammatory cascade of acne pathogenesis, including
      sebosuppressive and anti-inflammatory phytochemicals, and  small molecule
      inhibitors targeting sebaceous glands and enzymes, among others. Laser and light
      therapy is also being modified for the treatment of acne through combination
      methods with metal nanoshells and vacuum assistance. Probiotics have gained
      popularity in medicine as greater knowledge of the microbiome and its effects on
      multiple organ systems is being elucidated. Studies describing the positive
      effects of certain ammonia-oxidizing bacterial strains in the regulation of the
      skin's inflammatory response are ongoing. Therapies for acne are constantly
      evolving and current gold-standard acne therapy may be supplemented with novel
      treatment modalities in the near future.

PMID- 29594975
TI  - Hispanic Americans and Non-Hispanic White Americans Have a Similar Inflammatory
      Bowel Disease Phenotype: A Systematic Review with Meta-Analysis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a devastating immune-mediated
      disease on the rise in Hispanics living in the USA. Prior observational studies
      comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW)
      have yielded mixed results. AIMS: We performed a meta-analysis of observational
      studies examining IBD phenotype in Hispanics compared to NHW. METHODS: We
      conducted a systematic search of US-based studies comparing IBD subtype
      (Ulcerative Colitis: UC or Crohn's disease: CD) and phenotype (disease location
      and behavior) between Hispanics and NHW. We evaluated differences in age at IBD
      diagnosis, the presence of family history and smoking history. A random effects
      model was chosen "a priori." Categorical and continuous variables were analyzed
      using odds ratio (OR) or standard mean difference (SMD), respectively. RESULTS:
      Seven studies were included with 687 Hispanics and 1586 NHW. UC was more common
      in Hispanics compared to NHW (OR 2.07, CI 1.13-3.79, p = 0.02). Location of
      disease was similar between Hispanics and NHW except for the presence of upper
      gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32-1.06, p
      = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26-0.89, p = 0.02) or
      have a family history of IBD (OR 0.35, CI 0.22-0.55, p < 0.001). CD behavior
      classified by Montreal classification and age at IBD diagnosis were similar
      between Hispanics and NHW. CONCLUSION: UC was more common among US Hispanics
      compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For
      CD, disease behavior is similar, but Hispanics show a trend for less upper
      gastrointestinal involvement. A family history of IBD and smoking history were
      less common in Hispanics.

PMID- 29594977
TI  - Low Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Patients with
      Esophageal Food Impaction in Mexican Population.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is the most common cause of dysphagia
      and esophageal food impaction (EFI) in the USA, Western Europe, and Australia. In
      Mexico, the uncomplicated form of this disease is infrequent, and prevalence in
      patients with EFI is unknown. AIMS: To determine the prevalence and causes of
      EFI, endoscopic and therapeutic aspects, and establish the prevalence of biopsy
      proven EoE in patients with EFI. METHODS: Diagnostic upper gastrointestinal
      endoscopy reports from January 2011 to December 2016 were retrospectively
      reviewed. Patients with therapeutic procedures, gastrointestinal hemorrhage, or
      non-food foreign body impaction were excluded. The number of patients with EFI
      was determined. Additionally, patients with esophageal biopsy were retained for
      EoE prevalence calculation. The diagnosis of EoE was defined with the presence of
      eosinophil infiltration count >= 15/high-power field with or without typical
      endoscopic abnormalities. RESULTS: A total of 4700 reports of the same number of
      patients were selected; 2209 were males (47%) with a mean age of 57.6 +/- 12.3
      years (range 14-93). We identified 36 patients with EFI (0.76, 95% CI 0.51-1.01),
      16 males (44.4%) with a mean age of 54.9 +/- 19.7 (range 22-92). Esophageal
      biopsies were obtained in 17/36 (47.2%) cases. The diagnosis of EoE was confirmed
      in 2 patients (11.7%). Peptic stenosis was the most frequent cause of EFI.
      CONCLUSIONS: EoE is an infrequent cause of EFI in the Mexican population (11.7%).
      EoE had the lowest prevalence compared to that reported in Caucasian populations.
      The prevalence of EFI was also low.

PMID- 29594978
TI  - Latent Hepatitis Virus Reactivation Due to Drug Reaction: DRESSed to Kill?

PMID- 29594976
TI  - Efficacy of a Dexmedetomidine-Remifentanil Combination Compared with a Midazolam
      Remifentanil Combination for Conscious Sedation During Therapeutic Endoscopic
      Retrograde Cholangio-Pancreatography: A Prospective, Randomized, Single-Blinded
      Preliminary Trial.
AB  - BACKGROUND: Dexmedetomidine as a conscious sedative exhibits both analgesia and
      respiratory sparing effects. AIMS: We evaluated and compared the sedative effect
      and the safety of a dexmedetomidine-remifentanil (DR) regimen with a midazolam
      remifentanil (MR) combination during the endoscopic retrograde cholangio
      pancreatography (ERCP) requiring conscious sedation. METHODS: One-hundred and
      ninety-eight patients were randomized and divided into two groups. A bolus of
      midazolam (0.05 mg kg-1) was injected intravenously for MR group, and
      dexmedetomidine (1 MUg kg-1) was pumping for 10 min for DR group. Next, an
      initial loading dose of 1 MUg kg-1 and 0.05-0.2 MUg kg-1 min-1 of remifentanil
      was administered in all patients. Hemodynamic and respiratory changes, Ramsay
      Sedation Scale, Visual Analogue Scale, endoscopist and patient satisfaction were
      assessed. Furthermore, adverse events as well as recovery time and discharge time
      were rated. RESULTS: Patient satisfaction scores were significantly higher in the
      DR group compared with MR group. The occurrence of desaturation was statistically
      higher, and the operation time was longer in the MR group. Although no
      statistically significant values could be determined between the two groups about
      amnesia and need of additional drug, the DR group was found to require a
      significantly reduced amount of extra midazolam. Furthermore, nausea during
      catheterization of oropharynx was found to be more pronounced in the DR group.
      CONCLUSIONS: The dexmedetomidine-remifentanil protocol provided a parallel
      sedative efficacy and improved respiratory sparing effects. The higher patient
      satisfaction scores potentially offer a more reproducible ERCP quality. Adding
      dexmedetomidine to remifentanil can be used safely as a conscious sedation method
      during ERCP.

PMID- 29594979
TI  - Anti-inflammatory and Antioxidant Effects of Captopril Compared to
      Methylprednisolone in L-Arginine-Induced Acute Pancreatitis.
AB  - BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease mediated by damage
      in acinar cells and pancreatic inflammation with infiltration of leukocytes. The
      pancreatic renin-angiotensin system may play an important role in the
      pathogenesis of AP. AIM: The present study aimed to investigate the possible
      protective role of captopril (CAP), an angiotensin-converting enzyme inhibitor,
      in attenuating L-arginine-induced AP rat model and to elucidate the underlying
      molecular mechanisms. METHODS: Forty-eight adult male Wister rats were divided
      into four equal groups: control group (vehicle, orally for 10 days), AP group (3
      g/kg L-arginine, single i.p.) on 10th day of the experiment, CAP group (50 mg/kg
      captopril, orally, once daily), and MP group (30 mg/kg methylprednisolone,
      orally, once daily). CAP and MP were administered for 10 days prior to L-arginine
      injection. Rats were sacrificed 24 h after arginine injection. Inflammatory
      biomarkers; tumor necrosis factor alpha (TNF-alpha) concentration,
      myeloperoxidase (MPO) activity, and inducible nitric oxide synthase (iNOS) gene
      expression were determined in pancreas. Oxidative stress biomarkers; pancreatic
      nitric oxide (NO) and reduced glutathione (GSH) concentrations were measured.
      Moreover, serum alpha-amylase and lipase activities were measured and
      histopathological studies of the pancreas were done. RESULTS: CAP group showed a
      significant reduction in pancreatic TNF-alpha concentration, MPO activity, NO
      concentration, and downregulation of iNOS gene expression compared to AP group.
      CAP group also showed a significant increase in GSH concentration with
      amelioration of histological changes of AP as well as MP group. CONCLUSION:
      Captopril treatment showed a protective and comparable effect with MP treatment
      in AP rat model.

PMID- 29594981
TI  - History solves the mystery: an unusual cause of hypercalcemia.

PMID- 29594980
TI  - Is Young Adulthood a Critical Period for Suicidal Behavior among Sexual
      Minorities? Results from a US National Sample.
AB  - The developmental timing of suicide-related disparities between heterosexuals and
      sexual minorities (i.e., lesbian/gay and bisexual (LGB) people) is an
      understudied area that has critical prevention implications. In addition to
      developmentally situated experiences that shape risk for suicidality in the
      general population, sexual minorities also experience unique social stressors
      (e.g., anti-LGB stigma) that may alter their risk for suicidal behavior at
      different ages. Using a nationally representative US sample of adults, we
      assessed age-varying rates of suicidal behavior among heterosexuals and sexual
      minorities ages 18 to 60 and the age-varying association between anti-LGB
      discrimination and suicidal behavior. We also tested whether these age-varying
      prevalences and associations differed for men and women and for sexual minorities
      who did and did not endorse a sexual minority identity. Results indicate a
      critical period for suicide behavior risk for sexual minorities during young
      adulthood, with the highest rates of risk at age 18 followed by a steady decline
      until the early 40s. Disparities were particularly robust for sexual minorities
      who identified as lesbian, gay, or bisexual. This pattern was present for both
      men and women, though sexual minority women in their 30s were more likely to
      report suicidal behavior than heterosexuals and sexual minority men. Sexual
      minorities who experienced anti-LGB discrimination were more likely to report
      suicidal behavior, but the significance of this association was limited to those
      under 30. The effect of discrimination on suicidal behavior was stronger among
      young adult sexual minority men, relative to sexual minority women, but was
      present for a wider age range for sexual minority women (until age 30) relative
      to sexual minority men (until age 25).

PMID- 29594982
TI  - Penile calciphylaxis in a patient on combined peritoneal dialysis and
      hemodialysis.
AB  - Calciphylaxis presents with painful purpura and intractable skin ulcers on the
      trunk and particularly the distal extremities, and it mainly occurs in patients
      on chronic dialysis. A 66-year-old man with renal failure due to diabetic
      nephropathy was on peritoneal dialysis alone for 1 year, followed by peritoneal
      dialysis combined with hemodialysis for 3 years. He developed calciphylaxis of
      the penis, which was diagnosed from the skin biopsy findings and clinical
      observation. To treat this condition, PD was stopped and HD was performed three
      times a week. In addition, warfarin therapy was discontinued and infusion of
      sodium thiosulfate was performed. The penile ulcers decreased in size and pain
      was markedly improved, so the patient was discharged from hospital. Following
      discharge, PD was resumed after changing the peritoneal dialysis fluid to
      bicarbonate-buffered dialysate. The penile ulcers eventually resolved completely.
      There have been very few reports about calciphylaxis in patients on combined
      dialysis modalities. In our patient, penile calciphylaxis progressed when lactate
      buffered peritoneal dialysis fluid was used and resolved after switching to
      bicarbonate-buffered fluid together with cessation of warfarin therapy and
      infusion of sodium thiosulfate.

PMID- 29594983
TI  - Persistent EcoHIV infection induces nigral degeneration in 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-intoxicated mice.
AB  - The widespread use of antiretroviral therapy for treatment of human
      immunodeficiency virus (HIV) infections has dramatically improved the quality and
      duration of life for HIV-positive individuals. Despite this success, HIV persists
      for the life of an infected person in tissue reservoirs including the nervous
      system. Thus, whether HIV exacerbates age-related brain disorders such as
      Parkinson's disease (PD) is of concern. In support of this idea, HIV infection
      can be associated with motor and gait abnormalities that parallel late-stage
      manifestations of PD including dopaminergic neuronal loss. With these findings in
      hand, we investigated whether viral infection could affect nigrostriatal
      degeneration or exacerbate chemically induced nigral degeneration. We now
      demonstrate an additive effect of EcoHIV on dopaminergic neuronal loss and
      neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      intoxication. HIV-1-infected humanized mice failed to recapitulate these EcoHIV
      results suggesting species-specific neural signaling. The results demonstrate a
      previously undefined EcoHIV-associated neurodegenerative response that may be
      used to model pathobiological aspects of PD.

PMID- 29594984
TI  - In vivo characterization of macrophage-tropic simian immunodeficiency virus
      molecular clones in rhesus macaques.
AB  - Macrophages are a major target of HIV/SIV infection and play an important role in
      pathogenesis by serving as viral reservoirs in the central nervous system.
      Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned
      from blood of a rhesus macaque with rapid disease progression and SIV-associated
      encephalitis. Here, we show that infectious molecular clone deSIV147 caused
      systemic infection in rhesus macaques following intravenous or intrarectal
      exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and
      found that animals were SIV-positive, with high plasma and CSF viral loads. These
      macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon,
      lung, and liver. Furthermore, accumulation of perivascular macrophages,
      multinucleated giant cells, and microgliosis was detected. These findings suggest
      that the neurotropic deSIV147 clone will be useful to study macrophage infection
      in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell
      reservoirs in brain and other anatomical sites, as well as test strategies for
      eradication.

PMID- 29594985
TI  - Zika virus outbreak in New Caledonia and Guillain-Barre syndrome: a case-control
      study.
AB  - Zika virus (ZIKV) infection has been associated with neurologic disorders
      including Guillain-Barre syndrome (GBS). In New Caledonia during the ZIKV
      outbreak (2014-2015), case-control and retrospective studies have been performed
      to assess the link between ZIKV and GBS. Among the 15 cases included, 33% had
      evidence of a recent ZIKV infection compared to only 3.3% in the 30 controls
      involved. All patients were Melanesian, had facial diplegia and similar
      neurophysiological pattern consistent with acute inflammatory demyelinating
      polyneuropathy, and recovered well. Furthermore, during the peak of ZIKV
      transmission, we observed a number of GBS cases higher than the calculated upper
      limit, emphasizing the fact that ZIKV is now a major trigger of GBS.

PMID- 29594988
TI  - [Association between the dental caries and the human leucocyte antigen DQB1
      allele polymorphisms among the Uygur and Han children in Xinjiang].
AB  - OBJECTIVE: This study aims to investigate the association between human leucocyte
      antigen (HLA)-DQB1 allele polymorphisms and the presence dental caries among the
      Uygur and Han children in Xinjiang. METHODS: HLA-DQB1 allele in the Uygur and Han
      children with dental caries and healthy control in Xinjiang was tested (n=40)
      using the polymerase chain reaction-sequence specific primer (PCR-SSP) DNA
      parting technology. RESULTS: A total of five specific loci were detected in the
      HLA-DQB1 locus among the Uygur and Han children. The frequency of the HLA-DQB1*02
      allele in the Han group with severe caries (12.5%) was significantly lower than
      in the control group (32.5%) (P<0.05, OR=0.297). Moreover, the frequency of the
      HLA-DQB1*05 allele in the Uygur group with severe caries (37.5%) was
      significantly higher than in the control group (17.5%) (P<0.05, OR=2.829).
      CONCLUSIONS: Caries susceptibility among the Uygur and Han children in Xinjiang
      is related to the HLA-DQB1 allele. The HLA-DQB1*02 allele may protect against
      caries among the Han children, whereas the HLA-DQB1*05 allele may be responsible
      for the susceptibility of the Uygur children to caries.

PMID- 29594987
TI  - [Occlusion design of edentulous implant prosthesis].
AB  - The occlusion design of dental implants is related to the growing popularity of
      dental implantology. This paper discusses the occlusion design of the edentulous
      implant prosthesis and the relationships between stress change and the alveolar
      bone and between the occlusal design and implantation complications. The
      horizontal relationship of condyle, the design of the canine-guided occlusion,
      and the similarities and differences between the dental implant and the natural
      teeth on biteforce response are mentioned.

PMID- 29594986
TI  - Efficient Expression of an Alzheimer's Disease Vaccine Candidate in the Microalga
      Schizochytrium sp. Using the Algevir System.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease, where beta
      amyloid (Abeta) plays a key role in forming conglomerated senile plaques. The
      receptor of advanced glycation end products (RAGE) is considered a therapeutic
      target since it transports Abeta into the central nervous system, favoring the
      pathology progression. Due to the lack of effective therapies for AD, several
      therapeutic approaches are under development, being vaccines considered a
      promising alternative. Herein, the use of the Algevir system was explored to
      produce in the Schizochytrium sp. microalga the LTB:RAGE vaccine candidate.
      Algevir relies in an inducible geminiviral vector and led to yields of up to 380
      ug LTB:RAGE/g fresh weight biomass at 48-h post-induction. The Schizochytrium
      produced LTB:RAGE vaccine retained its antigenic activity and was highly stable
      up to temperatures of 60  degrees C. These data demonstrate the potential of
      Schizochytrium sp. as a platform for high production of thermostable recombinant
      antigens useful for vaccination against AD.

PMID- 29594989
TI  - [Influence of dexamethasone on the cell polarity and PAR complex of the embryonic
      epithelial cells in the palate].
AB  - OBJECTIVE: This study aims to investigate whether dexamethasone (DEX) can down
      regulate the PAR complex and disrupt the cell polarity in the palatal epithelium
      during palatal fusion. METHODS: Pregnant rats were randomly divided into control
      and DEX groups, which were injected intraperitoneally with 0.9% sodium chloride
      (0.1 mL) and DEX (6 mg.kg -1), respectively, every day from E10 to E12. The
      palatal epithelial morphology was observed using hematoxylin and eosin staining
      and scanning electron microscopy. Immunofluorescence staining, Western Blot
      analysis, and real-time polymerase chain reaction were performed to detect the
      expression of PAR3, PAR6, and aPKC. RESULTS: The incidence of cleft palate in DEX
      group (46.15%) was significantly higher than that in control group (3.92%), and
      the difference was statistically significant (chi2=24.335, P=0.00). DEX can also
      retard the growth of the palatal shelves and the short palatal shelves. The
      morphology and arrangement of MEE cells changed from polarized bilayer cells to
      nonpolarized monolayer ones. Additionally, the spherical structure decreased,
      which caused the cleft palate. PAR3 and PAR6 were only detected in the palatal
      epithelium, and aPKC was expressed in the palatal epithelium and mesenchyme. DEX
      can reduce the expression levels of PAR3, PAR6, and aPKC in the protein and gene
      levels. CONCLUSIONS: DEX can down-regulate the complex gene expression in the MEE
      cells, thereby destroying the cell polarity and causing cleft palate.

PMID- 29594990
TI  - [Preparation and characterization of oriented scaffolds derived from cartilage
      extracellular matrix and silk fibroin].
AB  - OBJECTIVE: This study aims to prepare oriented scaffolds derived from a cartilage
      extracellular matrix (CECM) and silk fibroin (SF) and use to investigate their
      physicochemical property in cartilage tissue engineering. METHODS: Oriented SF
      CECM scaffolds were prepared from 6% mixed slurry (CECM:SF=1:1) through modified
      temperature gradient-guided thermal-induced phase separation, followed by freeze
      drying. The SF-CECM scaffolds were evaluated by scanning electron microscopy
      (SEM) and histological staining analyses and determination of porosity, water
      absorption, and compressive elastic modulus of the materials. RESULTS: The SEM
      image showed that the SF-CECM scaffolds contained homogeneous reticular porous
      structures in the cross-section and vertical tubular structures in the
      longitudinal sections. Histological staining showed that cells were completely
      removed, and the hybrid scaffolds retained proteogly can and collagen. The
      composition of the scaffold was similar to that of natural cartilage. The
      porosity, water absorption rate, and vertical compressive elastic modulus of the
      scaffolds were 95.733%+/-1.010%, 94.309%+/-1.302%, and (65.40+/-4.09) kPa,
      respectively. CONCLUSIONS: The fabricated SF-CECM scaffolds exhibit satisfactory
      physicochemical and biomechanical properties and thus could be an ideal scaffold
      in cartilage tissue engineering.

PMID- 29594991
TI  - [Neurotrophin 3 promotes osteogenic differentiation of human dental follicle
      cells].
AB  - OBJECTIVE: This study aims to investigate the effect of neurotrophin 3 (NT-3) on
      the osteogenic differentiation of human dental follicle cells (hDFCs). METHODS:
      hDFCs were isolated and cultured in vitro. Immunocytochemical staining was used
      to identify the origin of hDFCs. The effects of different NT-3 concentrations on
      hDFCs proliferation were detected by using CCK-8 assay. The alkaline phosphatase
      (ALP) activities and mRNA expression levels of bone morphogenetic protein-2 (BMP
      2) and osteocalcin (OCN) were determined to investigate the effects of NT-3 on
      hDFCs osteogenesis. The difference in the number of mineralized nodules was
      detected using alizarin red staining. RESULTS: Vimentin and cytokeratin staining
      results showed that hDFCs originated from the mesenchymal cells. NT-3 exerted no
      evident effect on hDFCs proliferation. The ALP activity and the BMP-2 and OCN
      mRNA expression levels of hDFCs were significantly improved under treatment with
      different NT-3 concentrations (25, 50, and 100 ng.mL -1) compared with those in
      the control group. BMP-2 and OCN mRNA relative expression levels of hDFCs reached
      the highest when the NT-3 concentration was 100 ng.mL -1. The number of
      mineralized nodules reached the maximum when the hDFCs were treated with 50 and
      100 ng.mL -1 NT-3. CONCLUSIONS: Appropriate mass concentration of NT-3 can
      promote the osteogenic differentiation of hDFCs.

PMID- 29594992
TI  - [Expression and clinical significance of proline-rich tyrosine kinase 2 and
      phospho-protein kinase B in tongue squamous cell carcinoma].
AB  - OBJECTIVE: This study aimed to investigate the expression and clinical
      significance of proline-rich tyrosine kinase 2 (Pyk2) and phospho-protein kinase
      B (p-AKT) in tongue squamous cell carcinoma (TSCC) and adjacent nontumor tissues.
      METHODS: The Pyk2 and p-AKT protein levels were detected via immunohistochemistry
      in 45 cases of TSCC tissues and 30 cases of adjacent nontumor tissues. The
      relationships of the two protein levels and clinicopathological characteristics
      were also analyzed. RESULTS: Pyk2 and p-AKT levels were significantly higher in
      the TSCC tissues than in the adjacent nontumor tissues (P<0.05). Nontumor tissues
      showed poor or no expression. The expression levels of the two proteins were
      positively correlated (gammas=0.412). The expression of Pyk2 was associated with
      histopathological differentiation type, regional lymph node metastasis, and TNM
      staging (P<0.05), but not with age and gender. The expression of p-AKT was only
      related to histopathological differentiation types (P<0.05). CONCLUSIONS: The
      abnormal expression of Pyk2 and p-AKT proteins might be closely related to the
      development and progression of TSCC. Joint detection can be used as an indicator
      to estimate the degree of TSCC.

PMID- 29594993
TI  - [Experimental study of demineralized dentin matrix on osteoinduction and related
      cells identification].
AB  - OBJECTIVE: The aim of this study was to explore the theoretical framework of
      cells and the forms of osteogenesis in the mechanism by which demineralized
      dentin matrix (DDM) induces osteogenesis. METHODS: A total of 24 New Zealand
      rabbits were used in this study. A total of 4 erector spinae bags were created in
      each animal. A total of 3 erector spinae bags were implanted with DDM by random
      selection, whereas the remaining one erector spinae bag was not implanted with
      DDM. The rabbits were sacrificed after 1, 2, 3, 4, 8, 12, 16, and 20 weeks, and
      the samples were obtained. The samples were examined by hematoxylin-eosin (HE),
      tartrate-resistant acid phosphatase (TRAP), and immunohistochemical staining to
      identify the mesenchymal stem cells, osteoblasts, chondrocytes, and osteoclasts.
      RESULTS: The results of HE staining showed that in the third week, cartilage- and
      bone-like matrices, as well as the osteoblast-like cells, were observed. The
      results of immunohistochemical staining showed that the expressions of CD44,
      alkaline phosphatase (ALP), and collagen II were statistically significant
      ?(P<0.05). CONCLUSIONS: DDM has good histocompatibility and osteoinduction. In
      addition, induced ectopic osteogenesis mode mainly occurs in the endochondral
      bone.

PMID- 29594994
TI  - [K (lysine) acetyltransferase 2A affects the osteogenic differentiation of
      periodontal ligament stem cells through the canonical Wnt pathway].
AB  - OBJECTIVE: This study aims to investigate the mechanism of K (lysine)
      acetyltransferase 2A (KAT2A) regulation and control on the osteogenic
      differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The
      expression levels of KAT2A in PDLSCs were compared from each generation of the
      normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A
      gene interference on the osteogenic differentiation of PDLSCs were also detected.
      In addition, the influences of the KAT2A gene interference to the canonical Wnt
      pathway and ligands were detected. The upstream and down-stream relationships
      between KAT2A and canonical Wnt pathway were also determined. RESULTS: The
      decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each
      generation was compared with that in PDLSCs from the healthy tissue, and the
      difference was statistically significant (P<0.05). When the KAT2A gene was
      disrupted, the osteogenesis ability of PDLSC was declined, and the difference was
      statistically significant (P<0.05). The canonical Wnt pathway was activated, and
      the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the
      osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was
      unaffected. CONCLUSIONS: The KAT2A expression in PDLSCs was decreased because of
      perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic
      differentiation of the cells.

PMID- 29594995
TI  - [Antibacterial dental adhesive containing nanoantibacterial inorganic fillers].
AB  - OBJECTIVE: This investigation aimed to develop a novel antibacterial dental
      adhesive containing nanoantibacterial inorganic fillers and measure the dentin
      bonding strength, mechanical properties, and antibacterial property of the novel
      adhesive in vitro. METHODS: Novel nanoantibacterial inorganic fillers containing
      quaternary ammonium salt with long chain alkyl were synthesized on the basis of
      previous research. These novel nanoantibacterial inorganic fillers were added
      into the dental adhesive to prepare novel nanoantibacterial dental resin
      composite at mass fractions of 0%, 2.5%, 5.0%, 7.5%, and 10%; 0% was used as
      control. Dentin shear bonding test was used to evaluate the bonding strength.
      Flexural test was utilized to measure the novel resin composite flexural strength
      and elastic modulus. A dental plaque microcosm biofilm model with human saliva as
      inoculum was formed. Colony forming unit, lactic acid production, and live/dead
      assay of the biofilm on novel dental adhesive were calculated to assess the
      effect of novel dental adhesive on human dental plaque microcosm biofilm.
      RESULTS: The dentin shear bond strength, flexural strength, and elastic modulus
      were 28.9 MPa, 86.6 MPa, and 4.2 GPa, respectively, when the nanoantibacterial
      inorganic filler mass fraction in the dental adhesive reached approximately 5.0%.
      Consequently, the dentin shear bond strength and mechanical properties
      significantly increased. Addition of 2.5% nanoantibacterial inorganic fillers
      into the dental adhesive exerted no adverse effect on the mechanical properties
      significantly (P>0.05). Dental adhesive containing 5% or more nanoantibacterial
      inorganic fillers inhibited the metabolic activity of the dental plaque microcosm
      biofilm significantly, thereby displaying a strong antibacterial potency
      (P<0.05). CONCLUSIONS: This novel antibacterial dental adhesive, which contained
      5.0% nanoantibacterial inorganic filler, exhibited promising bonding strength,
      mechanical property, and antibacterial ability. Hence, this adhesive can be
      potentially used in caries inhibition in dental application.

PMID- 29594996
TI  - [Cosmetic technique application on the modification of lip deformity after cleft
      lip surgery].
AB  - OBJECTIVE: This study aims to explore the effect of cosmetic technique on the
      modification of lip deformity after cleft lip surgery. METHODS: A total of 35
      patients with postoperative cleft lip and who needed two-stage repair due to the
      nasolabial deformity were selected. Cosmetic technique was used to modify their
      lip deformities prior to the surgery. Front photos of the patients were taken
      before and after modification of their lip deformities. These photos were
      subsequently assessed by both the patients and the medical staff. The visual
      analogue method, Asher-McDade aesthetic index, and Mortier PB scale were used by
      patients and medical staff to evaluate changes in the lip shape by the cosmetic
      technique. RESULTS: Prior to the cosmetic technique application, the mean self
      score of the patients and the mean scores of the medical staff were 56+/-13 and
      3.22+/-1.11 points, respectively. After the cosmetic technique application, the
      mean self-score of the patients and the mean scores of the medical staff were
      67+/-12 and 2.85+/-1.03 points, respectively. The differences were statistically
      significant for both the patients and the medical staff (P<0.05). CONCLUSIONS:
      Appropriate use of the cosmetic technique can modify the lip deformity after the
      cleft lip surgery to a certain degree. The use of this technique exerts evident
      effects in restoring the symmetry?of lip peak and the continuity of the labial
      arch and in highlighting the philtrum column.

PMID- 29594997
TI  - [Reliability study in the measurement of the cusp inclination angle of a
      chairside digital model].
AB  - OBJECTIVE: This study aims to evaluate the reliability of the software Picpick in
      the measurement of the cusp inclination angle of a digital model. METHODS: Twenty
      one trimmed models were used as experimental objects. The chairside digital
      impression was then used for the acquisition of 3D digital models, and the
      software Picpick was employed for the measurement of the cusp inclination of
      these models. The measurements were repeated three times, and the results were
      compared with a gold standard, which was a manually measured experimental model
      cusp angle. The intraclass correlation coefficient (ICC) was calculated. RESULTS:
      The paired t test value of the two measurement methods was 0.91. The ICCs between
      the two measurement methods and three repeated measurements were greater than
      0.9. The digital model achieved a smaller coefficient of variation (9.9%).
      CONCLUSIONS: The software Picpick is reliable in measuring the cusp inclination
      of a digital model.

PMID- 29594998
TI  - [Application of bone-support guide by three-dimensional printing technique in
      maxillary LeFortIosteotomy].
AB  - OBJECTIVE: This study aimed to investigate the application of an osteotomy
      template and a repositioning template manufactured by three-dimensional (3D)
      printing technique in maxillary LeFortIosteotomy. METHODS: The patient group
      consisted of eight patients with maxillary hypoplasia who underwent
      LeFortIosteotomy. The mean age at the time of surgery was 25.6 years old. All
      patients were scanned using cone beam computed tomography (CBCT) to create a 3D
      model of the maxillary. The osteotomy and repositioning templates of the
      LeFortIosteotomy were manufactured by 3D printing technique. All bones were cut
      by the same doctor with extensive orthognathic surgery experience. One part of
      the template guided the osteotomy, and the other repositioned the maxilla during
      operation. Postoperative CBCT scan was performed, and the virtual plan was
      compared with the postoperative surgical result using an image fusion of the CBCT
      dataset by analyzing measurements between six landmarks relative to three
      reference planes. Statistical analysis was performed, and accuracy was reported
      using SPSS 16.0 software package. RESULTS: Primary healing of incisions was
      observed in all patients, and no serious complications were observed. The maximum
      mean values were 1.35 mm, and the displacement error was UL6 to the coronal
      plane. The maximum standard deviation was 0.85, and the maximum standard error
      was 0.30, which was acceptable by clinical standards. CONCLUSIONS: The
      application of osteotomy and repositioning templates manufactured by 3D printing
      technique in maxillary LeFortIosteotomy was safe and can enable doctors to
      complete a surgery accurately.

PMID- 29594999
TI  - [Comparative study on the shade matching performance of dental students under D55
      and D65 light sources conditions].
AB  - OBJECTIVE: This study aimed to compare the effect of D55 and D65 light sources on
      the visual colorimetry performance of dental students by using a homemade light
      source shelf. METHODS: Two Vitapan 3D-Master shade guides were randomly selected.
      One set was used as shade guides. Ten commonly used shade tabs of 2L2.5, 2M2,
      2R2.5, 3M2, 3R2.5, 3L1.5, 3R1.5, 3L2.5, 4R1.5, and 4L1.5 were selected from the
      other set with covered value marks and numbered from 1 to 10. After the
      colorimetric training, 49 undergraduate dental students were randomly divided
      into two groups. Each student randomly selected two of the 10 shade tabs, and the
      colors were subsequently matched under D65 and D55 light sources from a distance
      of approximately 40 cm. The average color difference (DeltaE) between the color
      selected by each participant and the actual color of shade tabs was calculated.
      Paired t test was used for statistical analysis. RESULTS: The DeltaE values
      between the color selected by each participant and the actual color of the shade
      tabs under the D55 light source varied from 0 to 6.540. The average value was
      2.501. The DeltaE values between the color selected by each participant and the
      actual color of the shade tabs under the D65 light source varied from 0 to 6.610.
      The average value was 2.530. No statistically significant difference was observed
      between the results under the two light sources (P=0.921). CONCLUSIONS: Both D55
      and D65 daylight lamps can be used for daily dental colorimetry. These two
      different color temperatures showed no significant difference.

PMID- 29595000
TI  - [Application of periodontal microsurgery in the augmentation of attached gingiva
      around an implant].
AB  - OBJECTIVE: This study aimed to evaluate the clinical effect of periodontal
      microscopic surgery on the augmentation of attached gingiva and determined the
      clinical principle on how to use minimally invasive surgery to improve the
      surgery success rate. METHODS: Twenty patients with insufficient attached gingiva
      around implants were selected. Periodontal microscopic surgery for free gingival
      graft was performed to increase the width of the attached gingiva around the
      implants. The survival state of the free gingiva was observed after surgery, and
      the width of the attached gingiva around the implants was recorded before and
      after surgery and 1 year after surgery. The shrinkage rate of the free gingival
      flap 1 year after surgery was analyzed to evaluate the stability of the flap.
      RESULTS: The flaps of the 20 cases all survived. One year after the operation,
      the width of the attached gingiva was (3.05+/-0.44) mm, which increased compared
      with that of preoperation (2.56+/-0.31) mm?and decreased compared with that of
      postoperative day (2.13+/-0.28) mm. The shrinkage rate of the attached gingiva
      was 41.22%+/-5.04%. CONCLUSIONS: The application of microscopic surgery on the
      augmentation surgery of attached gingiva can increase the success rate and
      improve the quality and quantity of attached gingiva around implants.

PMID- 29595001
TI  - [Experimental research on Arginine-gingipain A gene vaccine from Porphyromonas
      gingivalis that prevents peri-implantitis in Beagle dogs].
AB  - OBJECTIVE: This study aims to use Arginine-gingipain A gene vaccine (pVAX1-rgpA)
      to immunize adult Beagle dogs and to evaluate its effect during peri-implantitis
      progression and development. METHODS: Plasmid pVAX1-rgpA was constructed. The
      second and third bilateral mandible premolars of 15 adult Beagle dogs were
      extracted, and the implants were placed immediately. After 3 months, the animals
      were randomly divided into groups A, B, and C. Afterward, the animals were
      immunized thrice with plasmid pVAX1-rgpA, with heat-killed Porphyromonas
      gingivalis, or pVAX1, respectively. IgG in the serum and secretory IgA (sIgA) in
      saliva were quantitatively analyzed by enzyme-linked immunosorbent assay before
      and after 2 weeks of immunization. Peri-implantitis was induced with cotton
      ligatures fixed around the neck of implants. Probing depth (PD) and bleeding on
      probing were recorded. All animals were sacrificed after ligaturation for 6
      weeks. Decalcified sections with thickness of 50 MUm were prepared and dyed with
      methylene blue to observe the bone phenotype around implants. RESULTS: Levels of
      serum IgG and sIgA in saliva were higher in groups A and B after immunization
      than before the process (P<0.05) and higher than those in group C (P<0.05).
      However, no difference was observed between groups A and B (P>0.05). At 4 and 6
      weeks after ligaturation, PD of the ligatured side in group C was higher than
      that in groups A and B (P<0.05). On the other hand, no difference was identified
      between groups A and B (P>0.05). Bone loss in group A was significantly lower
      than that of the other groups (P<0.05). Abundant inflammatory cells and bacteria
      were present in the bone loss area around the implants in the three groups, as
      identified through hard tissue section observation. However, group C presented
      the most number of inflammatory cells and bacteria in the bone loss area around
      the implants. CONCLUSIONS: IgG and sIgA can be generated by immunity with rgpA
      DNA vaccine, which can significantly slow down bone loss during experimental peri
      implantitis in dogs.

PMID- 29595002
TI  - [Disheveled 2 around the implant at an early stage of hyperlipidemic rats].
AB  - OBJECTIVE: This study aims to investigate the expression of disheveled 2 (Dvl2)
      around the implant of hyperlipidemic rats at an early stage after the
      implantation. METHODS: A total of 24 Wistar rats were divided equally into the
      experimental group fed with high-fat diet group and control group fed with a
      normal diet. After 8 weeks, the serum lipid levels were detected, and rats
      received implants in the femur metaphysis. Rats were sacrificed at 1, 3, and 5
      days after implantation, and the bones around implants were obtained. Methylene
      blue-acid fuchsin staining was performed to observe the implant-bone interface.
      Real-time polymerase chain reaction was performed on runt-related transcription
      factor 2 (Runx2), cathepsin K (CatK), and Dvl2. Dvl2 Western blot or
      immunoprecipitation, phosphorylation, and ubiquitination were also conducted.
      RESULTS: In the experimental group, less osteoblasts, lower expression of Runx2
      and Dvl2, and lower Dvl2 phosphorylation (P<0.05) than those of the control group
      were observed; furthermore, the CatK expression and Dvl2 ubiquitination were
      higher than those in the control group (P<0.05). CONCLUSIONS: Hyperlipidemia may
      suppress bone remodeling around the implant at an early stage by Dvl2 down
      regulation, phosphorylation, and up-regulated ubiquitination.

PMID- 29595003
TI  - [Current situation and prospect for orthodontic thermoplastic materials].
AB  - Aesthetic and comfortable transparent retainers and clear plastic appliances are
      becoming increasingly popular, and their components, especially thermoplastic
      materials, are gradually attracting widespread interest. Orthodontic
      thermoplastic materials are versatile polymers, and thus their properties, such
      as force delivery, force relaxation, and aging properties have been
      comprehensively studied. Meanwhile, blending modification technology has been
      applied for the acquisition of novel materials with enhanced characteristics. In
      this paper, we review the types and properties of thermoplastic materials, the
      development process they undergo, factors that influence their properties, and
      some development prospects.

PMID- 29595004
TI  - [Mechanisms and implications of cancer cell dormancy in head and neck carcinoma].
AB  - Disease metastasis and relapse in many cancer patients several years (even
      decades) after surgical remission have been recently acknowledged as cases of
      cancer dormancy. Although cases of minimal residual disease are well documented,
      knowledge on its biological mechanisms and clinical implications remains limited.
      To date, numerous reviews have summarized the three potential models that may
      explain this phenomenon, including the angiogenic, immunologic, and cellular
      dormancy. In this study, we discuss newly uncovered mechanisms governing tumor
      cell dormancy in head and neck cancer, emphasizing on the crosstalk between
      dormant tumor cells and their microenvironments. Additionally, we explore the
      mechanisms on the reactivation of dormant residual tumor cells in anatomical
      sites, including the lymph nodes and bone marrow.

PMID- 29595005
TI  - [Effect of inflammaging on periodontitis].
AB  - Inflammaging is the chronic, systematic, and controllable upregulation of a pro
      inflammation state with advancing age. Chronic low-grade inflammation accompanied
      by sustained stimuli is correlated with various age-related diseases (ARDs).
      Recent studies on ARDs have prompted further research interest in the inner
      mechanisms underlying inflammaging to establish prevention and treatment plans
      for inflammatory diseases. In this article, we discuss inflammaging and its
      significant role in periodontitis.

PMID- 29595006
TI  - [Recent achievements in the microbiological etiology of dental caries].
AB  - Dental caries is the most common chronic infectious disease of the oral cavity.
      The bacterium Streptococcus mutans is the sole pathogen that causes this disease.
      However, substantial evidence suggests that prevention and treatment strategies
      developed from traditional "cariogenic pathogen theory" are inefficient in
      reducing the prevalence of dental caries. An increasing number of individuals
      adopt the ecological view of the microbiota in the pathogenesis of dental caries.
      Recent technological improvements have enabled the detection and analysis of oral
      microorganisms, and many studies have focused on this area. The core microbiota
      is defined as a cluster of microbes playing critical roles in the initial and
      development phases of dental caries and may provide future direction for
      microorganism-related etiological studies.

PMID- 29595007
TI  - [Treatment of a patient with considerably thin alveolar bone and severe open
      bite].
AB  - This case report describes the treatment of a 25-year-old woman with a severe
      open bite. This patient presented a grade III open bite, considerably thin
      alveolar bone, and evident labial buccal and lingual root form. The open bite was
      corrected by fixed orthodontic treatment and masticatory exercises. However, the
      increased pressure in the labial muscle caused by lip muscle exercise suppressed
      the canines, which resulted in the protrusion of the apices of canine roots out
      of the alveolar bone. Afterward, HX brackets, instead of self-locking, were used
      and bonded reversely in the occlusal-gingival direction on the upper canines. The
      lip muscle exercises were decreased. After adjustment, the roots penetrated back
      into the cancellous bone, the severe open bite was corrected, and a normal
      overbite and overjet were achieved. ClassIcanine and molar relationships were
      established. The masticatory function and profile were both considerably
      improved. This case report showed that a severe nonskeletal open bite can be
      corrected using orthodontic treatments combined with masticatory exercises.

PMID- 29595008
TI  - [Image of the month : A pediatric case of necrotizing pneumoniae].

PMID- 29595009
TI  - [Low back and radicular pain : which management in 2018 ?]
AB  - Both frequent reason for consultation and cause of absence at work, low back pain
      is a notorious public health concern. The Belgian Health Care Knowledge Centre
      (KCE) has been surrounded by 31 clinicians from different disciplines to develop
      a guideline covering the entire management of low back and radicular pain. A
      recently published guideline of the British National Institute for Health and
      Care Excellence (NICE) was largely used as a starting point and adapted to the
      Belgian context.

PMID- 29595010
TI  - [Asthma and obesity : preventable therapeutic trap, with careful follow-up].
AB  - Nowadays, more and more obese asthmatics visit a pulmonologist. It is proven that
      overweight stirs up the severity of the bronchopathy. It is a concept that is now
      anchored in the minds of most modern practitioners. Nevertheless, the idea that
      in some patients, excess weight can be an independent cause of the persistence of
      respiratory complaints, is sometimes neglected. This case report is about a
      severely obese poorly controlled asthmatic man, who turns out to be suffering
      from a concomitant obesity-hypoventilation syndrome. His clinical history
      confirms the necessity of quickly detecting this restrictive syndrome within an
      obstructive background, before its evolution towards a severe acute respiratory
      failure, where therapeutic approximations can have dramatic repercussions on the
      patient's health.

PMID- 29595011
TI  - [Incidental findings of maternal genetic abnormalities during non-invasive
      prenatal screening].
AB  - The non-invasive prenatal test (NIPT) has recently been added in our clinical
      practice. Sensitivity and specificity of this method in the common fetal
      aneuploidies screening is about 99 %. This technique remains a screening test,
      not a diagnosis test, because false positive or negative results exist. The
      discordant results are explained by the method itself witch analyses the whole
      free circulating DNA in the maternal blood: the fetal DNA from trophoblastic
      cells lysing but also the maternal DNA. Placenta confined mosaic is the main
      false positive cause reported in the literature. NIPT can rarely reveal maternal
      abnormalities. We are reporting two cases carrying a cytogenetic anomaly revealed
      with NIPT: microduplication of 22q11.2 and a sexual chromosomes anomaly.

PMID- 29595012
TI  - [Lyme disease or not ?]
AB  - Lyme disease is a complex pathology due to an infection by a spirochaete from the
      genus Borrelia. This infection results from a tick bite lasting more than 24
      hours. Signs and symptoms are numerous and are usually classified in three
      stages: early localized disease, early disseminated disease and late disease. The
      skin, the heart, the nervous system and the joints are mostly concerned. It is
      important to distinguish the clinical manifestations of the disease from those
      that are sometimes associated with it but with no scientific evidence. The
      purpose of this article is to insist on which signs and symptoms can be related
      to the disease and on those that usually are not. Diagnostic methods and
      treatments are also discussed.

PMID- 29595013
TI  - [Multidisciplinary management of alveolar echinococcosis : Echino-Liege Working
      Group].
AB  - Alveolar echinococcosis is a zoonotic disease due to the tapeworm Echinococcus
      multilocularis. The definitive host is the red fox. Until recently, Belgium was
      considered a country at very low risk for alveolar echinococcosis. However,
      recent studies carried out in southern Belgium have revealed, through post-mortem
      examination, high prevalences (up to 62 %) in foxes. Cats and dogs can act as
      definitive hosts. Human are accidentally infected by ingestion of food
      contaminated by the feces. After a long incubation period, invasive hepatic
      lesions may appear, as well as extra-hepatic lesions. The disease may be fatal.
      The diagnosis is based on imaging techniques, serology and nucleic acid detection
      in tissues. Early diagnosis may allow surgical removal of the lesion associated
      with at least 2 years of albendazole postoperative treatment. In case of
      contraindication to surgery, a long term treatment with albendazole is necessary.
      Liver transplantation is sometimes necessary. This article presents the
      epidemiologic, clinical, diagnostic and therapeutics features of this zoonotic
      disease.

PMID- 29595014
TI  - [Invasive diagnostic techniques for diffuse interstitial pneumopathies].
AB  - Interstitial lung diseases represent a very heterogeneous group of diseases
      mainly affecting connective lung tissue even if alveolar space may sometimes be
      involved. The identification of their etiology is the key stage in their
      management. It requires the integration of anamnestic, clinical, biological,
      radiological data and, sometimes relies on, cytology or histology. In this
      review, we assess the contribution and feasibility of the different invasive
      techniques used for interstitial lung disease diagnosis. In particular we focus
      on the yield of lung endoscopy in casting light on the multidisciplinary
      confrontation, which is the gold standard of the interstitial lung disease care
      management.

PMID- 29595015
TI  - [Update on developemental dyspraxia in children].
AB  - After having explained what is dyspraxia, we will briefly talk about narcissistic
      issues related to school term. Indeed, the defensive tools used by children to
      deal with learning disabilities are varied and not much specific, which will
      complicate the medical approach. Then we will describe the symptoms that are
      specific to search in the history and the first clinic appointment in cases of
      suspected dyspraxia. Finally, we will give details of how we must consider the
      exploration and the multidisciplinary taking over of the disorder.

PMID- 29595016
TI  - High-sensitivity terahertz imaging of traumatic brain injury in a rat model.
AB  - We demonstrated that different degrees of experimental traumatic brain injury
      (TBI) can be differentiated clearly in fresh slices of rat brain tissues using
      transmission-type terahertz (THz) imaging system. The high absorption region in
      THz images corresponded well with the injured area in visible images and magnetic
      resonance imaging results. The THz image and absorption characteristics of
      dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)
      stained microscopic images were investigated to account for the intrinsic
      differences in the THz images for the brain tissues suffered from different
      degrees of TBI and normal tissue aside from water. The THz absorption
      coefficients of rat brain tissues showed an increase in the aggravation of brain
      damage, particularly in the high-frequency range, whereas the cell density
      decreased as the order of mild, moderate, and severe TBI tissues compared with
      the normal tissue. Our results indicated that the different degrees of TBI were
      distinguishable owing to the different water contents and probable hematoma
      components distribution rather than intrinsic cell intensity. These promising
      results suggest that THz imaging has great potential as an alternative method for
      the fast diagnosis of TBI.

PMID- 29595017
TI  - Spectral refractive index assessment of turbid samples by combining spatial
      frequency near-infrared spectroscopy with Kramers-Kronig analysis.
AB  - A practical algorithm for estimating the wavelength-dependent refractive index
      (RI) of a turbid sample in the spatial frequency domain with the aid of Kramers
      Kronig (KK) relations is presented. In it, phase-shifted sinusoidal patterns
      (structured illumination) are serially projected at a high spatial frequency onto
      the sample surface (mouse scalp) at different near-infrared wavelengths while a
      camera mounted normally to the sample surface captures the reflected diffuse
      light. In the offline analysis pipeline, recorded images at each wavelength are
      converted to spatial absorption maps by logarithmic function, and once the
      absorption coefficient information is obtained, the imaginary part (k) of the
      complex RI (CRI), based on Maxell's equations, can be calculated. Using the data
      represented by k, the real part of the CRI (n) is then resolved by KK analysis.
      The wavelength dependence of n  (  lambda  )   is then fitted separately using
      four standard dispersion models: Cornu, Cauchy, Conrady, and Sellmeier. In
      addition, three-dimensional surface-profile distribution of n is provided based
      on phase profilometry principles and a phase-unwrapping-based phase-derivative
      variance algorithm. Experimental results demonstrate the capability of the
      proposed idea for sample's determination of a biological sample's RI value.

PMID- 29595018
TI  - Speckle attenuation by adaptive singular value shrinking with generalized
      likelihood matching in optical coherence tomography.
AB  - As a high-resolution imaging mode of biological tissues and materials, optical
      coherence tomography (OCT) is widely used in medical diagnosis and analysis.
      However, OCT images are often degraded by annoying speckle noise inherent in its
      imaging process. Employing the bilateral sparse representation an adaptive
      singular value shrinking method is proposed for its highly sparse approximation
      of image data. Adopting the generalized likelihood ratio as similarity criterion
      for block matching and an adaptive feature-oriented backward projection strategy,
      the proposed algorithm can restore better underlying layered structures and
      details of the OCT image with effective speckle attenuation. The experimental
      results demonstrate that the proposed algorithm achieves a state-of-the-art
      despeckling performance in terms of both quantitative measurement and visual
      interpretation.

PMID- 29595021
TI  - African Journal of Reproductive Health at 20: Looking Back and Looking Forward.

PMID- 29595020
TI  - Announcing a New Editor, African Journal of Reproductive Health.

PMID- 29595019
TI  - Validation of diffuse correlation spectroscopy sensitivity to nicotinamide
      induced blood flow elevation in the murine hindlimb using the fluorescent
      microsphere technique.
AB  - Nicotinamide has been shown to affect blood flow in both tumor and normal
      tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was
      used as a simple intervention to test the sensitivity of noninvasive diffuse
      correlation spectroscopy (DCS) to changes in blood flow in the murine left
      quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard
      fluorescent microsphere (FM) technique for validation. The nicotinamide dose
      response experiment showed that relative blood flow measured by DCS increased
      following treatment with 500- and 1000-mg  /  kg nicotinamide. The DCS and FM
      technique comparison showed that blood flow index measured by DCS was correlated
      with FM counts quantified by image analysis. The results of this study show that
      DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left
      quadriceps femoris. Additionally, the results of the comparison were consistent
      with similar studies in higher-order animal models, suggesting that mouse models
      can be effectively employed to investigate the utility of DCS for various blood
      flow measurement applications.

PMID- 29595022
TI  - Culture Clash: Shona (Zimbabwean) Migrant Women's Experiences with Communicating
      about Sexual Health and Wellbeing across Cultures and Generations.
AB  - This paper discusses the influence of cross-cultural modes of communication on
      perceptions of sexual health and wellbeing for Shona (Zimbabwean) women living in
      Australia and their children. Data was collected using focus groups in South
      Australia with fourteen women, between the ages of 29 and 53. Transcripts were
      analysed thematically. The women primarily constructed sexual health and
      wellbeing in customary Shona ways, which not only maintain secrecy about sexual
      health and wellbeing discourse, but also prohibit parents from talking to
      children about sexual health as such talk is reserved for particular kin and non
      kin relationships. These constructions however became more fluid the longer the
      women resided in Australia. For these women the notions of sexual health and
      wellbeing are a negotiation between Australian constructs and those from Shona
      culture, especially when applied to their children. This research highlights the
      potential influence of various cultural world views on sexual health
      communication among African migrant women and their children and questions the
      appropriateness of sexual health and wellbeing campaigns and their responsiveness
      for cross-cultural youth.

PMID- 29595023
TI  - Cost-Effectiveness Analysis of Family Planning Services Offered by Mobile Clinics
      versus Static Clinics in Assiut, Egypt.
AB  - Cost effectiveness studies of family planning (FP) services are very valuable in
      providing evidence-based data for decision makers in Egypt. Cost data came from
      record reviews for all 15 mobile clinics and a matched set of 15 static clinics
      and interviews with staff members of the selected clinics at Assiut Governorate.
      Effectiveness measures included couple years of protection (CYPs) and FP visits.
      Incremental cost-effectiveness ratios (ICER) and sensitivity analyses were
      calculated. Mobile clinics cost more per facility, produced more CYPs but had
      fewer FP visits. Sensitivity analysis was done using: total costs, CYP and FP
      visits of mobile and static clinics and showed that variations in CYP of mobile
      and static clinics altered the ICER for CYP from $2 -$6. Mobile clinics with
      their high emphasis on IUDs offer a reasonable cost effectiveness of $4.46 per
      additional CYP compared to static clinics. The ability of mobile clinics to reach
      more vulnerable women and to offer more long acting methods might affect a policy
      decision between these options. Static clinics should consider whether
      emphasizing IUDs may make their services more cost-effective.

PMID- 29595024
TI  - Effect of Volunteer Household Counseling in Improving Knowledge of Birth
      Preparedness and Complication Readiness of Pregnant Women in Northwest Nigeria.
AB  - Maternal and Child Health Integrated Program (MCHIP), a program by Jhpiego
      global, implemented maternal and newborn health project between 2006 and 2010 in
      Kano and Zamfara States, Nigeria. This was evaluated with an objective to
      characterize the effects of volunteer household counselors (VHCs) upon improving
      knowledge of birth preparedness and complication readiness (BPCR) among pregnant
      women. VHCs were trained to educate women and their families at home about BPCR.
      Knowledge of BPCR was compared among 152 and 594 women who did and did not
      receive household counseling. Mothers' knowledge of BPCR among those who did and
      did not receive counseling was 32.2% and 11.2% respectively. Mothers who received
      counseling had better knowledge of BPCR compared to women who did not (Relative
      Risk [R.R.] 2.30, 95% [C.I.] 1.50, 3.51, P = 0.0001) in a multivariable logistic
      regression model adjusting for potential confounders. Mothers who received
      counseling had better odds of knowledge of danger signs during delivery (R.R.
      1.48, 95% C.I. 1.05, 2.09, P = 0.02), and post-partum period (R.R. 1.69, 95% C.I.
      1.22, 2.32, P = 0.001), but not during pregnancy (R.R. 1.26, 95% C.I. 0.97, 1.64,
      P = 0.08), compared with women who received no counseling. VHCs can substantially
      increase knowledge of BPCR and danger signs among women in Nigeria.

PMID- 29595025
TI  - Contraceptives: Adolescents' Knowledge, Attitudes and Practices. A Case Study of
      Rural Mhondoro-Ngezi District, Zimbabwe.
AB  - Adolescent reproductive health behaviour has become an emerging world concern as
      the age at menarche and sexual debut has plummeted globally. The primary
      objective of the paper is to understand the importance of reproductive health
      education to contraceptive use among adolescents in Mhondoro-Ngezi District. The
      paper also investigates knowledge, attitudes, beliefs and practices (KABP)
      pertaining to contraceptive use among adolescents. Factors underlying KABP are
      further explored. In addition, this paper investigates the availability,
      accessibility, acceptability and affordability of contraceptives to adolescents.
      These issues are assessed from the perspective of all duty bearers (mothers,
      fathers, healthcare providers, religious leaders and secondary school teachers).
      The paper is based on a cross-sectional study which was conducted in Mhondoro
      Ngezi area. A total of 185 adolescents aged 15-19 years were sampled with a sex
      ratio of 67. The study triangulated both quantitative and qualitative methods of
      data collection. The results in this paper indicate that adolescents in Mhondoro
      Ngezi engage in early sexual debut. Despite the fact that knowledge about modern
      contraceptives is universal (96%) among adolescents in Mhondoro-Ngezi,
      contraceptive use is very low, 21%. Limited contraceptive use among adolescents
      in the study area is a result of the interplay of demographic, policy, socio
      cultural, religious and economic factors. The study has thus recommends that the
      government and other relevant stakeholders to formulate policies that promote
      reproductive education in order to foster the utilization of contraceptives by
      adolescents.

PMID- 29595026
TI  - Dual Protection and Contraceptive Method Use among Women in Heterosexual
      Relationships in Mahikeng, South Africa.
AB  - South African new reproductive health policies have given weight to dual
      protection as a public health intervention against unintended pregnancies and
      sexually transmitted infections. However, studies of dual protection have
      remained scanty and under researched in South Africa. This situation has left the
      reproductive health policy makers clueless about salient strategies to promote
      dual contraceptive method use. A survey of 568 women in steady relationships aged
      15-49 was conducted in Mahikeng Municipality. Using multivariate logistic
      regression independent predictors of contraceptive method use were examined and
      presented as odds ratio and 95% confidence intervals. Sixteen percent of the
      women were currently protecting against both unintended pregnancies and
      infectious diseases while 40% were protecting against unintended pregnancies
      only. Age, occupation, ever discussed condom use with partner; home language and
      religion were the independent predictors of dual method use. Non-barrier method
      use was associated with age, home language, religion, and duration of union. The
      study concludes that educative and enlightening programs that emphasize women's
      employment and communication about condom use may be specifically helpful in
      promoting dual method use.

PMID- 29595027
TI  - Covariates of Multiple Sexual Partnerships among Sexually Active Men in Lesotho.
AB  - Multiple sexual partnerships (MSP) have been identified as the main reason for
      the high rate of HIV prevalence in sub-Saharan Africa, including Lesotho. The aim
      of this paper is to identify the social and economic variables associated with
      MSP among men in Lesotho. The study used data from 2009 Lesotho Demographic and
      Health Survey. A sample of 2335 males in the age group 15-44 was used.
      Participants qualified if they were sexually active during the past year before
      the survey. Binary logistic regression was used to analyse the data. Results
      indicated that 29% of the respondents had engaged in sexual intercourse with
      multiple partners in the past year. Lower age at sexual debut, employment; having
      ever moved from home in the past year; believing that men have the right to have
      sex with other women; believing that beating a woman is justified if she argues
      with husband and having sex with casual partner were associated with an increased
      likelihood of MSP. On the other hand, coming from household led by a woman
      reduced the odds ratio. The study recommends that promotion of awareness
      programmes on MSP coupled with economic empowerment of women should be
      intensified in Lesotho.

PMID- 29595028
TI  - Making Abortion Safer in Rwanda: Operationalization of the Penal Code of 2012 to
      Expand Legal Exemptions and Challenges.
AB  - Penal code was revised in Rwanda in 2012 allowing legal termination of pregnancy
      resulting from rape, incest, forced marriage, or on medical grounds. An
      evaluation was conducted to assess women's access to abortion services as part of
      an ongoing program to operationalize the new exemptions for legal abortion. Data
      was collected from eight district hospitals; seven gender-based violence (GBV)
      centers and six intermediate courts. Three focus group discussions and 22 in
      depth interviews were conducted with key informants. At hospitals, of the 2,644
      uterine evacuation records (July 2012-June 2014), and 312 monitoring cases
      (August-December 2014), majority of all uterine evacuations (97% and 85%
      respectively, for the two periods) were for obstetric conditions, and induced
      abortion on medical grounds accounted for 2% vs. 15% respectively. Medical
      abortion was the prominent method of uterine evacuation. At the GBV centers,
      3,763 records were identified retrospectively; 273 women were pregnant. Since the
      legal reform there was only one abortion for a pregnancy resulting from rape.
      Abortion stigma and court order requirement are major barriers to access
      services. The operationalization program has made significant contributions to
      make abortion safer in Rwanda but this evaluation demonstrates that further work
      is required to reach the goal of providing safe abortion services to all eligible
      women. Addressing abortion stigma at the community, organizational and structural
      levels; further strengthening of service provision; and streamlining legal
      requirements to protect particularly young women from sexual violence and making
      abortion a realistic option for GBV victims are some of the important next steps.

PMID- 29595029
TI  - Satisfaction Determinants of Women during Childbirth in Health Facilities in
      Senegal: Literature Review.
AB  - This article presents the results of the literature review performed on the main
      conceptual models used in the measurement of the satisfaction of women during
      childbirth in health facilities and the main determinants of their satisfaction.
      The review focused on PubMed, Google scholar and Public Health data. Several
      conceptual models for measuring satisfaction were found through the literature.
      It is clear from this review that a multitude of determinants are associated with
      women's satisfaction such as health care provider's attitude, the environment as
      well as the socio-demographic, economic and even psychological characteristics of
      the patient herself. These results were used to develop a conceptual framework
      for measuring the satisfaction of women who gave birth in Senegal health
      facilities.

PMID- 29595030
TI  - The Effectiveness of a Collector Bag for Measurement of Post-partum Hemorrhage.
AB  - The aim of the study was to assess sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV) of collector bag and its correlation
      with hemoglobin (Hb) and hematocrit (Ht) variations. This study, carried on 100
      women referred for admission to labor ward of Shohada hospital in Orumeyeh City,
      Iran, from April to November, 2007. Serum Hb and Ht were measured after
      admission; a collecting bag placed under the pelvis just after birth and was
      weighted after delivery. Hb and Ht were again assessed at 8 hr after delivery.
      PPH was defined as blood loss ?500 ml following vaginal delivery. Each 500 ml
      blood loss accounts for approximately a 3% change in the Ht level or a falling in
      Hb of 1 g/dl. With this cut off our noted Sensitivity=80%, Specificity=95. 7%,
      PPV= 88.9% and NPV= 91.8%. The collector bag is a rapid and precise instrument to
      diagnose of postpartum hemorrhage in the delivery room. It also enables a visual,
      quantitative and objective estimation of blood loss.

PMID- 29595031
TI  - Maternal and Child Health Services in the Context of the Ebola Virus Disease:
      Health Care Workers' Knowledge, Attitudes and Practices in Rural Guinea.
AB  - The objective of this study was to document maternal and child health care
      workers' knowledge, attitudes and practices on service delivery before, during
      and after the 2014 EVD outbreak in rural Guinea. We conducted a descriptive cross
      sectional study in ten health districts between October and December 2015, using
      a standardized self-administered questionnaire. Overall 299 CHWs (94% response
      rate) participated in the study, including nurses/health technicians (49%),
      midwives (23%), managers (16%) and physicians (12%). Prior to the EVD outbreak,
      87% of CHWs directly engaged in managing febrile cases within the facility, while
      the majority (89% and 63%) referred such cases to another facility and/or EVD
      treatment centre during and after the EVD outbreak, respectively. Compared to the
      period before the EVD outbreak when approximately half of CHWs (49%) reported
      systematically measuring body temperature prior to providing any care to
      patients, most CHWs reported doing so during (98%) and after the EVD outbreak
      (88%). The main challenges encountered were the lack of capacity to screen for
      EVD cases within the facility (39%) and the lack of relevant equipment (10%). The
      majority (91%) of HCWs reported a decrease in the use of services during the EVD
      outbreak while an increase was reported by 72% of respondents in the period
      following the EVD outbreak. Infection prevention and control measures established
      during the EVD outbreak have substantially improved self-reported provider
      practices for maternal and child health services in rural Guinea. However, more
      efforts are needed to maintain and sustain the gain achieved.

PMID- 29595032
TI  - Contraceptive Use, Unwanted Pregnancies and Abortions among Hairdressers in
      Ibadan, Southwest Nigeria.
AB  - The study was conducted in Ibadan, Southwest Nigeria to determine prevalence and
      predictors of contraceptive use, unwanted pregnancies and induced abortions among
      hairdressers. 1687 female hairdressers were surveyed using a cross sectional
      design and cluster sampling technique. Mean age was 27.0+/-8.1 years, 851 (50.4%)
      were single and 1005 (59.6%) qualified hairdressers. 817 (56.8%) of sexually
      active were currently using contraception. Attainment of secondary school
      education was a predictor of contraceptive use; OR=1.4, 95% CI (1.1-1.8). 429
      (29.8%) ever had an unwanted pregnancy; 26.5 % among singles, 32.3 % among
      married. Predictors of unwanted pregnancies were age >30years; OR=1.9, 95% CI
      (1.4-2.5) and being a qualified hairdresser; OR=1.6, 95% CI (1.2-2.2). 347
      (24.1%) ever had an induced abortion; 21.5.0 % of singles, 26% of married. Being
      married; OR=5.2, 95% CI (2.2-11.9) was the only predictor of induced abortion.
      Prevalence of unwanted pregnancies and abortions were high especially among
      married hairdressers.

PMID- 29595033
TI  - Surgical Treatment of Complication of Female Genital Mutilation in Pikine
      Hospital, Senegal.
AB  - We share our experience on reconstructive for surgery female genital mutilation.
      This is a retrospective study of all cases of female genital mutilation surgery
      performed in Pikine National Hospital. We have reviewed the various indications
      and surgical techniques used. We collected 8 cases of clitoral cyst and 6 cases
      of closed vaginal opening. The surgery of clitoral cysts was to perform
      cystectomy followed by nymphoplasty. The closing of the vaginal opening required
      defibulation together with clitoroplasty according to the wishes of the patient.
      The anatomical and functional outcomes were satisfactory. Female genital
      mutilation surgery requires a good knowledge of vulvar anatomy. The various
      surgical indications must meet the expectations of patients to guarantee their
      satisfaction.

PMID- 29595034
TI  - Retrograde intra-renal surgery under spinal anesthesia: the first large series.
AB  - BACKGROUND: Retrograde intra-renal surgery (RIRS) has become increasingly common
      and is mainly performed under general anesthesia (GA). There are no specific
      papers about RIRS performed under spinal anesthesia (SA). Our objective was to
      evaluate feasibility and results of RIRS performed under SA. METHODS: We analyzed
      all consecutive RIRS performed for stones in day surgery from March 2008 to
      September 2012. Single procedures outcomes of RIRS performed under SA were
      evaluated with US and KUB X-ray at 2 weeks. Further treatments, operative time
      and complications were also evaluated. Outcomes of RIRS performed under SA and GA
      were compared. Difference between groups was statistically analyzed. Significance
      level was set at P<0.05. RESULTS: One hundred thirty-nine RIRS under SA and 47
      under GA were considered. Mean stone burden was 14+/-6 mm. No case of conversion
      from SA to GA occurred. Stone-free rate (SFR) level 4U of RIRS under SA and under
      GA were respectively 63.6% and 48.6%, SFR level 0U 24.5% and 25.7%, CIRF 39.1%
      and 22.9%. Further treatments were performed respectively in 20.8% and in 23.4%.
      No anesthesia-related and Clavien-Dindo grade >=3 complications occurred. No
      statistically significant difference was found in stone-free rates, CIRF and
      significant residual fragments rates, need for further procedures, operative time
      and complications between the two groups. CONCLUSIONS: RIRS under SA seems
      feasible and effective for renal stones in day surgery. Results seem equivalent
      to RIRS under GA. SA can be considered for RIRS as an alternative to GA.

PMID- 29595035
TI  - Prognostic role of delay before radical cystectomy: retrospective analysis of a
      single-centre cohort with 376 patients.
AB  - BACKGROUND: According to International Guidelines radical cystectomy (RC) should
      not be delayed over 90 days to prevent the risk of intercurrent progression and
      worse survival. Nevertheless, such a recommendation relies on a few retrospective
      studies reaching non-univocal conclusions. Aim of the present study was to
      investigate if the latency between diagnosis and cystectomy (LDC) is related to
      prognosis after RC. METHODS: Retrospective analysis of database collecting
      complete information on patients undergone RC at single institution since 2004.
      The cases with an LDC <15 or >360 days or submitted to neo-adjuvant chemotherapy
      or with distant metastasis were excluded. Uni- and multivariate analyses assessed
      the relationship between LDC upstaging, progression-free and overall survival.
      RESULTS: The data of 376 patients were analyzed; mean/median LDC was 83/76 days
      and 124 patients (33%) had LDC>90 days. LDC was shorter in younger patients with
      first diagnosis of more advanced BC at clinical staging; accordingly, patients
      with LDC<90 days had more advanced disease also at final pathology. Prevalence of
      pathological upstaging was 37%; in case of upstaging LDC was 75 days vs. 72 days
      (P=0.4629). Multivariable regression models adjusted for pathological local and
      lymph nodal stage showed that LDC, continuous or dichotomized at
      30/60/90/120/180/240 days was not related to progression-free or overall
      survival. The retrospective design of study is the main limitation of the study.
      CONCLUSIONS: In our experience nor the risk of upstaging, neither survival after
      RC were related to LDC. Even if these results should not discourage any effort to
      perform surgery expeditiously, the window of opportunity for RC might not be
      delimited by a predetermined threshold.

PMID- 29595036
TI  - Association between lncRNA H19 (rs217727, rs2735971 and rs3024270) polymorphisms
      and the risk of bladder cancer in Chinese population.
AB  - BACKGROUND: The Long non-coding RNA (lncRNA) H19 is involved in carcinogenesis,
      progression, and metastasis. However, the association between genetic variants in
      H19 and bladder cancer susceptibility has not been reported. This case-control
      study assessed the association between H19 genetic variants and susceptibility to
      bladder cancer in a Chinese Han population. METHODS: In this study, 200 patients
      with bladder cancer and 200 healthy controls were surveyed and compared for
      frequencies of the genotypes of the H19 gene. Logistic regression analysis and
      the chi-square test were employed as statistical methods. Odds ratio (OR) and its
      corresponding 95% confidence interval (95% CI) were calculated to estimate the
      strength of association between H19 polymorphisms and risk of bladder cancer.
      RESULTS: We analyzed the frequency of three lncRNA H19 SNPs in 200 bladder cancer
      patients and 200 healthy controls. Carriers of variant rs217727 heterozygous
      genotype showed increased bladder cancer risk (P = 0.008). Further stratified
      analyses revealed that the association between bladder cancer risk and variant
      genotypes of rs217727 was more profound in smokers. Furthermore, decreased risk
      of invasive bladder cancer was found in carrying rs3024270 CC patients.
      CONCLUSIONS: Our results provided the evidence that rs217727 in H19 was
      associated with elevated risk of bladder cancer, which may be a potential
      biomarker for predicting bladder cancer susceptibility. Furthermore, invasive
      bladder cancer in carrying rs3024270 CC genotype maybe have a good prognosis.

PMID- 29595037
TI  - Expandable metallic ureteral stent: indications and results.
AB  - INTRODUCTION: Ureteral obstructions are managed by complex surgery not always
      feasible for surgical field complexity or poor patient conditions. Various
      surgical maneuvers, as ureteral dilation, stenting and percutaneous nephrostomy,
      can be offered, but they are related to considerable failure rates and negative
      impact on quality of life. In selected cases, the positioning of long-term
      expandable metallic ureteral stents (EMUSs) may be an appropriate and successful
      choice. EVIDENCE ACQUISITION: Following the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses criteria, a systematic review of the
      literature was performed in July 2017 using PubMed, Cochrane Library, Scopus and
      Web of Science databases. The search was conducted by typing the following terms:
      "Expandable metallic ureteral stent," "Memokath ureteral stent," "Allium ureteral
      stent," and "Uventa ureteral stent." EVIDENCE SYNTHESIS: Twenty studies reported
      the safety, efficacy and clinical outcomes related to the common available EMUSs.
      Most studies were single-arm, retrospective and involving a low number of
      clinical cases, resulting in significant difficulties with outlining indications
      and drawing conclusions. Available papers showed EMUSs offered a high rate of
      patency, a long duration and a good quality of life, even if they are associated
      with significant complications. CONCLUSIONS: Since the first description of
      ureteral stents 50 years ago, we have faced a significant evolution in stent
      design. The current generation of EMUSs offers many advantages, but the onset of
      adverse effects is still significant and limits their use to selected cases.
      Further research should be addressed to the realization of prospective, multi
      institutional randomized clinical trials to highlight indications to manage
      appropriately ureteral obstructions.

PMID- 29595038
TI  - The relationship between lower urinary tract symptoms and irritable bowel
      syndrome: a meta-analysis of cross-sectional studies.
AB  - INTRODUCTION: While several epidemiologic studies have investigated the
      relationship between lower urinary tract symptoms (LUTS) and irritable bowel
      syndrome (IBS), it remains unclear. To investigate the relationship between IBS
      and LUTS, a systematic review and meta-analysis of cross-sectional studies was
      carried out. EVIDENCE ACQUISITION: Online databases were searched up to December
      1st, 2017 for cross-sectional studies that evaluated the association between IBS
      and the risk of LUTS. Summary odds ratios (ORs) and 95% confidence intervals (95%
      CIs) were calculated. EVIDENCE SYNTHESIS: In all, 9 articles that contained 19907
      participants and 2620 cases of LUTS were included in this meta-analysis. Compared
      with the non-IBS group, the IBS group had a higher risk of LUTS (total OR=2.11,
      95% CI: 1.91-2.33, P<0.00001). Patients with IBS were more likely to have urine
      storage symptoms (total OR=1.80, 95% CI: 1.34-2.42, P<0.0001). Subgroup analysis
      by gender showed that the IBS group had a higher risk of LUTS in both men (total
      OR=2.17, 95% CI: 1.82-2.58, P<0.00001) and women (total OR=1.85, 95% CI: 1.57
      2.17, P<0.00001). CONCLUSIONS: Our meta-analysis provides evidence that IBS is
      associated with an increased risk of LUTS in both men and women.

PMID- 29595039
TI  - An update on prostate biopsy in the era of magnetic resonance imaging.
AB  - INTRODUCTION: Prostate cancer (PCa) is a singular disease owing to absence of
      imaging technique able to detect suspicious glandular area at higher risk of
      disease. Nowadays, magnetic resonance imaging (MRI) has been used as a way to
      detect PCa and simplify targeting prostate biopsy (PB). The aim of this study is
      to review the most recent data regarding standard BP and MRI-guided PB. EVIDENCE
      ACQUISITION: A comprehensive systematic MEDLINE search was performed in December
      2017 for English-language reports by using the following terms: "prostate
      biopsy," "multiparametric magnetic resonance imaging," "prostate cancer,"
      "transrectal and transperineal ultrasound," "target biopsy." Previous published
      reviews and recent published original articles were preferred in order to meet
      our study scope. EVIDENCE SYNTHESIS: Retrieved studies of greater interest were
      reported in two main sections: standard PB and MRI-guided BP. Thus, the main
      items regarding PB were analyzed. Briefly, clinical suspicious of PCa is based on
      prostate specific antigen level and digital rectal examination findings although
      a PCa risk assessment through a nomogram risk calculator is nowadays advised. Ten
      eighteen biopsy cores, depending on prostate volume, and peripheral sampling seem
      the suitable scheme for initial biopsy while a saturation template (>20 cores
      including transitional prostate area) is widely used in case of repeat PB.
      Performing a local anesthesia is now the standard of care with several available
      techniques. No difference exists in term of PCa detection rate between
      transperienal and transrectal approaches however the last one is mostly used. The
      use of MRI-guided biopsy seems to be a promising imaging technique able to
      identify an index lesion at higher suspicious of PCa. In particular, MRI shows a
      higher accuracy than standard PB in the detection of clinically significant PCa.
      No general consensus exists on which MRI-guided biopsy should be used with three
      different ways currently available to take biopsy core. However, the initial MRI
      cognitive PB has been replaced by fusion MRI technique to guide biopsy with
      reproducible results. Absence of standardization founded in initial MRI studies
      has been recently revised by introduction of common criteria to assess PCa
      presence on MRI. CONCLUSIONS: PB is the cornerstone in diagnosis and management
      of PCa. Although ultrasound transrectal and transperineal PB are still considered
      as the standard, emerging data confirm the role of MRI-guided biopsy,
      particularly in patients with a previous negative biopsy. However, MRI costs and
      the moderate inter-reader reproducibility of the exam are still significant
      concerns requiring further studies to define the right role of MRI in the PCa
      diagnostic pathway.

PMID- 29595040
TI  - Male infertility as a proxy of the overall male health status.
AB  - INTRODUCTION: Male infertility (MI) has been widely associated with different
      comorbid conditions. The aim of this review is to summarize the available
      evidences investigating the link between MI cancer, chronic non-malignant
      conditions and overall health. EVIDENCE ACQUISITION: A literature search has been
      conducted using the MEDLINE/PubMed and Scopus databases for English-language
      original and review articles and selecting publications from January 2007 to June
      2017, although highly regarded older publications were also considered. The
      following key words and MeSH terms were combined: "male infertility," "semen
      analysis," "health," "comorbidities," "cancer," "metabolic syndrome," "diabetes,"
      "hypertension," "cardiovascular diseases," and "mortality." EVIDENCE SYNTHESIS:
      Several studies supported a higher risk of testis cancer for patients with MI;
      conversely, controversial findings have been reported on the association between
      prostate cancer and MI. Beside urogenital malignancies, melanoma, bladder,
      thyroid and hematological malignancies have been also more frequently reported
      among infertile men. Large cohort studies supported a significant association
      between diabetes mellitus, metabolic disorders and MI. Similarly, the risk of
      developing cardiovascular diseases appears to be higher among infertile men. Of
      note, a significant association between semen alterations and the overall burden
      of comorbidities, as well as the overall mortality, has been reported. A common
      genetic background appears as the main pathophysiological link between
      infertility and other comorbidities. CONCLUSIONS: Male infertility is a proxy of
      the overall male health status. Physicians should comprehensively assess men
      presenting for couple infertility and properly followed-up these patients given
      their higher risk of developing cancer.

PMID- 29595041
TI  - Time of catheterization as an independent predictor of early urinary continence
      recovery after radical prostatectomy.
AB  - BACKGROUND: The purpose of the present study was to investigate the potential
      impact of catheter removal time on immediate and early urinary continence
      recovery in a series of patients who underwent radical prostatectomy (RP).
      METHODS: We prospectively collected and analyzed the clinical records of 197
      patients who underwent open RP between January 2014 and December 2016. A single
      surgeon using the urethral fixation technique performed all procedures. Patients
      receiving surgery between Monday and Wednesday performed a cystogram on
      postoperative day (POD) 2. Conversely, other cases treated on a Thursday or
      Friday performed a cystogram on the following Monday (POD 3 or 4). The catheter
      removal was planned the day after the cystogram if there was a watertight
      anastomosis or with a little extravasation (<5%). Urinary continence recovery was
      evaluated 1 week, 1, 2 and 3 months after catheter removal. Patients self
      reporting no urine leak were considered continent. Logistic regression analysis
      was used to identify independent predictors of urinary continence recovery at
      different follow-up durations. RESULTS: The median catheterization time was 3
      (IQR: 3-4.2) days and acute urinary retention (AUR) was observed in 13 (6.5%)
      cases. At median follow-up of 12 (IQR: 9-12) months, no case of bladder neck
      contracture was observed. Urinary continence probabilities were 43%, 63%, 87%,
      91% and 95% after 1 week, 1, 3, 6, and 12 months, respectively. On multivariable
      analyses, time of catheter removal was an independent predictor of urinary
      continence recovery after 1 week (OR 1.2; P=0.02); 1 month (OR 1.2; P=0.01); 3
      months (OR 1.1; P=0.04) and 6 months (OR 1.1; P=0.03) after catheter removal.
      CONCLUSIONS: Time of catheterization should be considered as a postoperative
      parameter able to influence the immediate and early urinary continence recovery
      in patients undergoing RP. The impact of new surgical techniques on urinary
      continence recovery should be tested also considering such potential confounding
      factor.

PMID- 29595042
TI  - Does prostate volume have an impact on the functional and oncological results of
      Retzius-sparing robot-assisted radical prostatectomy?
AB  - BACKGROUND: The objective of our study is to evaluate the effect of prostatic
      volume on the outcomes of Retzius-sparing robot-assisted radical prostatectomy
      (RSP). METHODS: All the consecutive patients undergoing RSP up to January 2015
      were included. The series was divided into three groups based on prostate weight
      at radical prostatectomy specimen (<40 g, 40-60 g, >60 g). Perioperative,
      oncological and functional data were prospectively recorded. Potency was defined
      as erections sufficient for penetration; continence as no pad or one safety
      liner. Oncological results were reported as positive surgical margins (PSMs) and
      1-year biochemical disease-free survival (PSA<0.2 ng/mL). RESULTS: We evaluated
      750 patients (366 with <40 g prostates, 272 with 40-60 g prostates, 112 with >60
      g prostates). Median follow-up was 22 months; PSA was higher in larger prostates
      (6.6 vs. 6.8 vs. 8 ng/mL). Nerve-sparing and bladder-neck sparing procedures were
      in similar percentages. Larger prostates required longer surgeries (90 vs. 100
      vs. 100 minutes, P=0.002). Perioperative results were similar (blood loss,
      discharge, complications, catheter removal). Larger prostates had more frequently
      localized disease (pT2 in 49.5% vs. 60.7% vs. 68.5%; P=0.001); PSMs were similar
      both in pT2 (15.5% vs. 9.4% vs. 11.8%) and in pT3 cases (40.1% vs. 42% vs. 34%).
      In the three study groups, immediate continence was reached by 88%, 89.5% and
      81.3% (P=0.045), while no differences were observed concerning continence (93.4%,
      94.1%, 94.7%; P=0.892) or potency after follow-up. CONCLUSIONS: RSP is feasible
      in patients with prostates of any volume, with similar oncological and functional
      outcomes. Despite being inferior to the figures obtained in low volume prostates,
      the very high immediate continence rates observed in larger prostates encourage
      the use of this approach also in larger prostates.

PMID- 29595043
TI  - Minimally invasive approach for the management of urological complications after
      renal transplantation: single center experience.
AB  - BACKGROUND: The aim of the study was to characterise urological complications
      after renal transplantation and to evaluate the role of minimally invasive
      management for urological complications. METHODS: A total of 920 kidney
      transplantations were performed between 2008 and 2015. All patients were followed
      up for at least 1 year after transplantation. Complications regarded as
      urological were urinary leakage, ureteral stricture, urinary malignancy, bladder
      outlet obstruction (BOO) and urinary calculi. We evaluated data from the time of
      occurrence of urological complications and the type of the management prescribed.
      RESULTS: Among 920 transplantations performed in our clinic, 41 (4.4%) urological
      complications arose. Twenty (48.8%) of the complications occurred during the
      first 3 months and 21 (51.2%) occurred after 3 months, postoperatively. Ureteral
      strictures were found in 14 (34.1%) patients, urinary tract stones in seven
      (17%), BOO in 6 (14.6%) and urinary leakage was observed in 5 (12.1%) patients.
      Ureteral stricture was managed with endoscopic approach in eight (61.3%)
      patients. Urinary tract stones and urinary leakage were managed in 7 (100%) and 4
      (75%) patients with endoscopic approach. Overall 29 (70.7%) of 41 urological
      complications were managed with endourological approaches. CONCLUSIONS: It is
      likely that the importance of open surgery could decrease in the future.
      Endoscopic management of urological complications have come to have an important
      role in the treatment of urological complications after transplantation.

PMID- 29595045
TI  - The endoscopic surgical resection of intrasellar lesions conserves the hormonal
      function: a negative correlation to the microsurgical technique.
AB  - BACKGROUND: The endonasal endoscopic approach is still currently under
      investigation for sellar tumour surgery: a higher resection rate is to be
      expected and complications should be minimized. The authors report their surgical
      results of endonasal endoscopic neurosurgery with special focus on postoperative
      hypopituitarism in comparison to microsurgical procedures. METHODS: Sixty
      patients received endoscopic endonasal transsphenoidal procedures for sellar
      pathologies. All patients were followed up prospectively. A second group of 60
      patients received microsurgical transsphenoidal procedures for sellar pathologies
      in our neurosurgical department before and were prospectively followed until now.
      Special attention was paid to hormonal insufficiency and medical substitution.
      RESULTS: Sixty-eight percentage (41/60) of the patients who underwent
      microsurgical procedures showed a new persisting pituitary insufficiency
      postoperatively. Twenty-three patients (55.5%) were substituted with thyroxine,
      hydrocortisone and sexual hormones and one patient (2.5%) also with ADH cause of
      global pituitary insufficiency. In 19 cases without any hormonal insufficiency
      after microsurgical procedures 9 patients (47%) showed remnant tumor in follow up
      MRI. The patients who underwent endoscopic procedures for pituitary adenomas
      revealed significant (p<0.01) less new persistent hormonal insufficiency with 13%
      of all cases (8/60). Five patients (62.5%) were substituted with thyroxine and
      hydrocortisone, two patients (25%) substituted with thyroxine, hydrocortisone and
      sexual hormones and one patient also with ADH because of global pituitary
      insufficiency. Thereby, in follow up MRI and hormonal testing, radical tumour
      resection was detected in 92% in the endoscopic group. CONCLUSIONS: This study
      seems to indicate that a better intraoperative identification and preservation of
      pituitary gland is possible in endoscopic transsphenoidal surgery with
      consecutive lower postoperative hypopituitarism rate.

PMID- 29595044
TI  - Robotic-assisted laparoscopic repair of ureteral injury: an evidence-based review
      of techniques and outcomes.
AB  - INTRODUCTION: Iatrogenic ureteral injuries represent a common surgical problem
      encountered by practicing urologists. With the rapidly expanding applications of
      robotic-assisted laparoscopic surgery, ureteral reconstruction has been an
      important field of recent advancement. This collaborative review sought to
      provide an evidence-based analysis of the latest surgical techniques and outcomes
      for robotic-assisted repair of ureteral injury. EVIDENCE ACQUISITION: A
      systematic review of the literature up to December 2017 using PubMed/Medline was
      performed to identify relevant articles. Those studies included in the systematic
      review were selected according to Preferred Reporting Items for Systematic
      Reviews and Meta-analysis criteria. Additionally, expert opinions were included
      from study authors in order to critique outcomes and elaborate on surgical
      techniques. A cumulative outcome analysis was conducted analyzing comparative
      studies on robotic versus open ureteral repair. EVIDENCE SYNTHESIS: Thirteen case
      series have demonstrated the feasibility, safety, and success of robotic ureteral
      reconstruction. The surgical planning, timing of intervention, and various
      robotic reconstructive techniques need to be tailored to the specific case,
      depending on the location and length of the injury. Fluorescence imaging can
      represent a useful tool in this setting. Recently, three studies have shown the
      feasibility and technical success of robotic buccal mucosa grafting for ureteral
      repair. Soon, additional novel and experimental robotic reconstructive approaches
      might become available. The cumulative analysis of the three available
      comparative studies on robotic versus open ureteral repair showed no difference
      in operative time or complication rate, with a decreased blood loss and hospital
      length of stay favoring the robotic approach. CONCLUSIONS: Current evidence
      suggests that the robotic surgical platform facilitates complex ureteral
      reconstruction in a minimally invasive fashion. High success rates of ureteral
      repair using the robotic approach mirror those of open surgery, with the
      additional advantage of faster recovery. Novel techniques in development and
      surgical adjuncts show promise as the role of robotic surgery evolves.

PMID- 29595046
TI  - Brain arteriovenous malformations: an ongoing challenge.

PMID- 29595047
TI  - Natural history of brain arteriovenous malformations: systematic review.
AB  - INTRODUCTION: The appropriate interpretation of natural history of brain
      arteriovenous malformations (bAVMs) and of factors that negatively affect the
      risk of future hemorrhage are important when recommending management pathways.
      With the present systematic review, we aim to provide an overview of the
      available evidence on natural history of brain arteriovenous malformations
      (bAVMs), focusing on hemorrhage rates and risk factors for future hemorrhage.
      EVIDENCE ACQUISITION: We performed a systematic literature analysis using the
      Ovid Medline database, encompassing English language studies (published between
      1980 and 2018) reporting the natural history of untreated bAVMs. Annual
      hemorrhage rates in both unruptured and previously ruptured bAVMs, as well as
      risk factors for future hemorrhage were extracted for analysis. EVIDENCE
      SYNTHESIS: Eighteen studies with a total of 8418 bAVM-cases could be extracted
      from the literature. Seventeen studies reported annual hemorrhage rates and ten
      studies reported risk factors for future hemorrhage. The average annualized
      hemorrhage rate was 2.2% for unruptured bAVMs and 4.3%, for bAVMs that presented
      with hemorrhage. Prior hemorrhage and deep AVM location could be identified as
      most consistently reported risk factors for future hemorrhage. CONCLUSIONS:
      Previously ruptured bAVMs have a higher annual hemorrhage rate than unruptured
      bAVMs. Deep bAVM location and prior hemorrhage may increase the risk for
      subsequent hemorrhage.

PMID- 29595048
TI  - The cobra effect: a venomous snake in the neurosurgical field.

PMID- 29595049
TI  - Adjusting the Linear Range of Au-MOF Fluorescent Probes for Real-Time Analyzing
      Intracellular GSH in Living Cells.
AB  - A series of Au-loaded metal-organic frameworks (MOFs) were synthesized in this
      study and further employed for real-time quantitative analysis of intracellular
      glutathione (GSH) level. Different linear ranges can be acquired by altering the
      size of gold and MOF particles, or adjusting the proportion of 2
      aminoterephthalic acid/1,4-benzenedicarboxylate linkers, which is also observed
      on fluorescein isothiocyanate-attached Au-MOFs. Further study reveals that the
      flexible molecular chain of GSH with the -COOH/-NH2 and -SH terminals may readily
      tie on relevant gold nanoparticles through its -NH2/-COOH groups, which then
      restricts the intramolecular motions of fluorescence probes and thus induces
      marked fluorescence enhancement. On the basis of these observations, the
      intracellular GSH levels of different cells including L02 cells, Hela, and U87 as
      well as HepG2 cancer cells can be rapidly evaluated by these Au-MOF probes.

PMID- 29595050
TI  - Nanozymatic Antioxidant System Based on MoS2 Nanosheets.
AB  - The enzymatic antioxidant system (EAS) protects aerobic cells from oxidative
      stress. However, it is brittle and susceptible of inactivation of reactive oxygen
      species (ROS) immoderate production. Here, we demonstrated that MoS2 nanosheets
      (few-layer MoS2), as a multifunctional nanozyme, possess intrinsic activity of
      mimicking enzymes of superoxide dismutases (SODs), catalases (CATs), and
      peroxidases (PODs) under physiological conditions (pH 7.4, 25  degrees C).
      Further, MoS2 nanosheets showed POD-like activity by transferring electrons
      instead of generating ROS. Similar to EAS, a defense termed nanozymatic
      antioxidant system (NAS) was developed by MoS2 nanosheets, for regulation of
      oxidative stress. Surprisingly, this NAS can effectively scavenge other free
      radicals including hydroxyl radicals (*OH), nitrogen-centered free radicals
      (*DPPH), and nitric oxide (*NO). To evaluate these unique properties of MoS2
      based NAS in vivo, Escherichia coli ( E. coli), Staphylococcus aureus ( S.
      aureus), and A549 cell models were established, respectively. These results
      showed MoS2 nanosheets superiorly protect bacteria and cells against oxidative
      injury caused by H2O2. This work makes MoS2 nanosheets promising antioxidants in
      the pathological processes and expands their application in biocatalysis and nano
      biomedicine.

PMID- 29595051
TI  - Construction of Highly Efficient Resonance Energy Transfer Platform Inside a
      Nanosphere for Ultrasensitive Electrochemiluminescence Detection.
AB  - Electrochemiluminescence (ECL) detection has attracted increasing attention as a
      promising analytical approach. A considerable number of studies showed that ECL
      intensity can be definitely improved by resonance energy transfer (RET), while
      the RET efficiency is strongly dependent on the distance between exited donors
      and acceptors. Herein we disclose for the first time a highly enhanced RET
      strategy to promote the energy transfer efficiency by coencapsulating the donor
      ([Ru(bpy)3]2+)/acceptor (CdTe quantum dots, CdTe QDs) pairs into a silica
      nanosphere. Plenty of [Ru(bpy)3]2+ and CdTe QDs closely packed inside a single
      nanosphere greatly shortens the electron-transfer path and increases the RET
      probability, therefore significantly enhancing the luminous efficiency. Further
      combining with molecularly imprinting technique, we develop a novel ECL sensor
      for ultrasensitive and highly selective detection of target molecules. Proof of
      concept experiments showed that extremely low detection limits of subfg/mL (S/N =
      3) with broad linear ranges (fg/mL to ng/mL) could be obtained for detection of
      two kinds of mycotoxins (alpha-ergocryptine and ochratoxin A) that are recognized
      as potential health hazards at very low concentrations. This strategy combining
      enhanced RET system and molecularly imprinting technique, represents a versatile
      ECL platform toward low-cost, rapid, ultrasensitive, and highly selective
      detection of target molecules in diverse applications.

PMID- 29595052
TI  - Mucoadhesion of Progesterone-Loaded Drug Delivery Nanofiber Constructs.
AB  - Mucoadhesive delivery systems have attracted remarkable interest recently,
      especially for their potential to prolong dosage form resident times at sites of
      application such as the vagina or nasal cavity, thereby improving convenience and
      compliance as a result of less frequent dosage. Mucoadhesive capabilities need to
      be routinely quantified during the development of these systems. This is however
      logistically challenging due to difficulties in obtaining and preparing viable
      mucosa tissues for experiments. Utilizing artificial membranes as a suitable
      alternative for quicker and easier analyses of mucoadhesion of these systems is
      currently being explored. In this study, the mucoadhesive interactions between
      progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content)
      and either artificial (cellulose acetate) or mucosa membranes are investigated by
      texture analysis and results across models are compared. Mucoadhesion to
      artificial membrane was about 10 times that of mucosa, though statistically
      significant ( p = 0.027) association between the 2 data sets was observed.
      Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and
      unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical
      mucoadhesion theories, was tested to determine its validity. Points of
      interaction between the fiber and mucosa membrane were examined using atomic
      force microscopy (AFM) to determine the depths of interpenetration and unfilled
      voids/roughness, features crucial to mucoadhesion according to the diffusion and
      mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma
      tests established a monotonic relationship between detaching forces and
      roughness, significant with p-values of 0.014 and 0.027, respectively. A similar
      relationship between CMC concentration and interfacial roughness was also
      confirmed. We conclude that AFM analysis of surface geometry following
      mucoadhesion can be explored for quantifying mucoadhesion as data from
      interfacial images correlates significantly with corresponding detaching forces,
      a well-established function of mucoadhesion.

PMID- 29595053
TI  - Polysorbasome: A Colloidal Vesicle Contoured by Polymeric Bioresorbable
      Amphiphiles as an Immunogenic Depot for Vaccine Delivery.
AB  - To accomplish an innovative vaccine design, there are two key challenges:
      developing formulations that avoid cold chain shipment and finding a delivery
      vehicle that is absorbable in vivo. Here, we explored the design and performance
      of a colloidal vesicle that enabled us to consider both challenges. We used
      polymeric bioresorbable amphiphiles as surface-active agents for stabilizing
      oily/aqueous interfaces and formed a colloidal vehicle named polysorbasome (PSS,
      polymeric absorbable vesicle), without using conventional emulsifiers such as
      sorbitan esters or their ethoxylates. Homogenizing the oil/water compartments
      forms a colloid containing an aqueous solution in its core and provides an oily
      barrier that isolates the encapsulated material from external materials. In this
      form, the PSS serves as a depot for sustained delivery of vaccine antigens.
      Following vaccination, the antigen-specific antibodies and the cell-mediated
      immunity can be manipulated after the antigen being formulated with PSS
      particles. Then, the degradability intrinsic to the polymeric bioresorbable
      amphiphiles complies with the destruction and further absorbance of the vehicles
      in vivo. The structural features of these versatile vesicles based on
      bioresorbable amphiphilic engineering may provide new insights into vaccine
      delivery.

PMID- 29595055
TI  - Coumarin-Based Oxime Esters: Photobleachable and Versatile Unimolecular
      Initiators for Acrylate and Thiol-Based Click Photopolymerization under Visible
      Light-Emitting Diode Light Irradiation.
AB  - Developing efficient unimolecular visible light-emitting diode (LED) light
      photoinitiators (PIs) with photobleaching capability, which are essential for
      various biomedical applications and photopolymerization of thick materials,
      remains a great challenge. Herein, we demonstrate the synthesis of a series of
      novel PIs, containing coumarin moieties as chromophores and oxime ester groups as
      initiation functionalities and explore their structure-activity relationship. The
      investigated oxime esters can effectively induce acrylates and thiol-based click
      photopolymerization under 450 nm visible LED light irradiation. The initiator O-3
      exhibited excellent photobleaching capability and enabled photopolymerization of
      thick materials (~4.8 mm). The efficient unimolecular photobleachable initiators
      show great potential in dental materials and 3D printings.

PMID- 29595054
TI  - High-Output Lead-Free Flexible Piezoelectric Generator Using Single-Crystalline
      GaN Thin Film.
AB  - Piezoelectric generators (PEGs) are a promising power source for future self
      powered electronics by converting ubiquitous ambient mechanical energy into
      electricity. However, most of the high-output PEGs are made from lead zirconate
      titanate, in which the hazardous lead could be a potential risk to both humans
      and environment, limiting their real applications. III-Nitride (III-N) can be a
      potential candidate to make stable, safe, and efficient PEGs due to its high
      chemical stability and piezoelectricity. Also, PEGs are preferred to be flexible
      rather than rigid, to better harvest the low-magnitude mechanical energy. Herein,
      a high-output, lead-free, and flexible PEG (F-PEG) is made from GaN thin film by
      transferring a single-crystalline epitaxial layer from silicon substrate to a
      flexible substrate. The output voltage, current density, and power density can
      reach 28 V, 1 MUA.cm-2, and 6 MUW.cm-2, respectively, by bending the F-PEG. The
      generated electric power by human finger bending is high enough to light
      commercial visible light-emitting diodes and charge commercial capacitors. The
      output performance is maintained higher than 95% of its original value after 10
      000-cycle test. This highly stable, high-output, and lead-free GaN thin-film F
      PEG has the great potential for future self-powered electronic devices and
      systems.

PMID- 29595056
TI  - Live Cell Imaging in Microfluidic Device Proves Resistance to Oxygen/Glucose
      Deprivation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
AB  - Analyses of cellular responses to fast oxygen dynamics are challenging and
      require ad hoc technological solutions, especially when decoupling from liquid
      media composition is required. In this work, we present a microfluidic device
      specifically designed for culture analyses with high resolution and magnification
      objectives, providing full optical access to the cell culture chamber. This
      feature allows fluorescence-based assays, photoactivated surface chemistry, and
      live cell imaging under tightly controlled pO2 environments. The device has a
      simple design, accommodates three independent cell cultures, and can be employed
      by users with basic cell culture training in studies requiring fast oxygen
      dynamics, defined media composition, and in-line data acquisition with optical
      molecular probes. We apply this technology to produce an oxygen/glucose deprived
      (OGD) environment and analyze cell mortality in murine and human cardiac
      cultures. Neonatal rat ventricular cardiomyocytes show an OGD time-dependent
      sensitivity, resulting in a robust and reproducible 66 +/- 5% death rate after 3
      h of stress. Applying an equivalent stress to human induced pluripotent stem cell
      derived cardiomyocytes (hiPS-CMs) provides direct experimental evidence for fetal
      like OGD-resistant phenotype. Investigation on the nature of such phenotype
      exposed large glycogen deposits. We propose a culture strategy aimed at depleting
      these intracellular energy stores and concurrently activate positive regulation
      of aerobic metabolic molecular markers. The observed process, however, is not
      sufficient to induce an OGD-sensitive phenotype in hiPS-CMs, highlighting
      defective development of mature aerobic metabolism in vitro.

PMID- 29595058
TI  - Inkjet Printing Based Droplet Generation for Integrated Online Digital Polymerase
      Chain Reaction.
AB  - We report on the development of a novel and flexible online digital polymerase
      chain reaction (dPCR) system. The system was composed of three parts: an inkjet
      for generating the droplets, a coiled fused-silica capillary for thermal cycling,
      and a laser-induced fluorescence detector (LIFD) for positive droplet counting.
      Upon inkjet printing, monodisperse droplets were continuously generated in the
      oil phase and then introduced into the capillary in the form of a stable
      dispersion. The droplets containing one or zero molecules of target DNA passed
      through the helical capillary that was attached to a cylindrical thermal cycler
      for PCR amplification, resulting in the generation of fluorescence for the DNA
      positive droplet. After 36 PCR cycles, the fluorescence signal intensity was
      detected by laser-induced fluorescence located at the downstream of the
      capillary, followed by a positive/negative counting. The present system was
      successfully applied to the absolute quantification of the HPV sequence in Caski
      cells with dynamic ranges spanning 4 orders of magnitude.

PMID- 29595057
TI  - Accurately Predicting Disordered Regions of Proteins Using Rosetta
      ResidueDisorder Application.
AB  - Although many proteins necessitate well-folded structures to properly instigate
      their biological functions, a large fraction of functioning proteins contain
      regions-known as intrinsically disordered protein regions-where stable structures
      are not likely to form. Notable functional roles of intrinsically disordered
      proteins are in transcriptional regulation, translation, and cellular signal
      transduction. Moreover, intrinsically disordered protein regions are highly
      abundant in many proteins associated with various human diseases, therefore these
      segments have become attractive drug targets for potential therapeutics. Over the
      past decades, numerous computational methods have been developed to accurately
      predict disordered regions of proteins. Here we introduce a user-friendly and
      reliable approach for the prediction of disordered protein regions using the
      structure prediction software Rosetta. Using 245 proteins from a benchmark data
      set (16 DisProt database proteins) and a test data set (229 proteins with NMR
      data), we use Rosetta to predict the global protein structures and then show that
      there is a statistically significant difference between Rosetta scores in
      disordered and ordered regions, with scores being less favorable in disordered
      regions. Furthermore, the difference in scores between ordered and disordered
      protein regions is sufficient to accurately identify disordered protein regions.
      As a result, our Rosetta ResidueDisorder method (benchmark data set prediction
      accuracy of 71.77% and independent test data set prediction accuracy of 65.37%)
      outperformed other established disorder prediction tools and did not exhibit a
      biased prediction toward either ordered or disordered regions. To facilitate
      usage, a Rosetta application has been developed for the Rosetta ResidueDisorder
      method.

PMID- 29595059
TI  - Chiral Sensing Platform Based on the Self-Assemblies of Diphenylalanine and
      Oxalic Acid.
AB  - Molecular self-assemblies offer a promising strategy for the synthesis of
      advanced materials for the construction of novel chiral sensing systems, and
      latest innovations on such self-assemblies are focused on simple building blocks
      in biology such as nucleic acids, lipids, and peptides. Herein, the self
      assemblies of diphenylalanine (FF) and oxalic acid (OA) were prepared as the
      chiral sensing device for the recognition of tryptophan (Trp) isomers.
      Interestingly, the self-assemblies composed of OA and FF with different charging
      states (neutral, positively charged, and negatively charged) exhibited quite
      different morphologies, resulting in significantly different chiral recognition
      ability toward the Trp isomers. Also, in this work, the temperature sensitivity
      and chiral selectivity of the proposed FF-OA self-assemblies were also studied.
      From a practical point of view, the FF-OA self-assemblies were finally applied
      for the determination of precise levels of d-Trp in the racemic mixture of Trp
      isomers.

PMID- 29595060
TI  - The effect of partner HIV status on motivation to take antiretroviral and
      isoniazid preventive therapies: a conjoint analysis.
AB  - Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are important
      to reduce morbidity and mortality among people newly diagnosed of HIV. The
      successful uptake of ART and IPT requires a comprehensive understanding of
      patients' motivation to take such therapies. Partners also play an important role
      in the decision to be initiated and retained in care. We quantified patients'
      motivation to take preventive therapies (ART and IPT) and compared by partner HIV
      status among people newly diagnosed of HIV. We enrolled and surveyed adults (>=18
      years) with a recent HIV diagnosis (<6 months) from 14 public primary care
      clinics in Matlosana, South Africa. Participants received eight forced-choice
      tasks comparing two mutually exclusive sub-sets of seven possible benefits
      related to preventive therapies. A linear probability model was fitted to
      estimate the probability of prioritizing each benefit. Tests of concordance were
      conducted across partner HIV status (no partner, HIV- or unknown, or HIV+). A
      total of 424 people completed surveys. At the time of interview, 272 (64%) were
      on ART and 334 (79%) had a partner or spouse. Keeping themselves healthy for
      their family was the most important motivator to take preventive therapies (p <
      0.001). Preventing HIV transmission to partners was also highly prioritized among
      participants with current partners independent of partner's HIV status (p <
      0.001), but it was least prioritized among those without current partners (p =
      0.72). Keeping themselves healthy was less prioritized. We demonstrate that
      social responsibility such as supporting family and preventing HIV transmission
      to partners may pose greater motivation for ART and IPT initiation and adherence
      compared to individual health benefits. These messages should be emphasized to
      provide effective patient-centered care and counseling.

PMID- 29595061
TI  - Continuous Glucose Monitoring Associated With Less Diabetes-Specific Emotional
      Distress and Lower A1c Among Adolescents With Type 1 Diabetes.
AB  - BACKGROUND: Psychosocial impact research of continuous glucose monitoring (CGM)
      and continuous subcutaneous insulin infusion (CSII) among adolescents with type 1
      diabetes (T1D) is limited. The present study assesses associations between
      diabetes technology use on adolescent- and parent-perceived diabetes-specific
      distress and A1c. METHOD: Adolescents with T1D and parents (N = 1040; primarily
      mothers) completed measures of diabetes distress. Adolescents were categorized by
      technology use: CGM Alone, CSII Alone, CGM+CSII, or No Technology. ANOVA,
      regression, and Cohen's d were used for group comparisons on measures of diabetes
      distress and A1c. Analyses also compared groups on clinical elevations of
      distress. RESULTS: CGM use was associated with less adolescent distress compared
      to No Technology ( d = 0.59), CGM+CSII ( d = 0.26), and CSII Alone ( d = 0.29).
      Results were similar but with smaller effect size for parent-reported distress,
      although CGM+CSII showed equivocal association with parent distress compared to
      No Technology ( d = 0.18). CGM Alone was associated with lower A1c compared to No
      Technology ( d = 0.48), to CSII Alone ( d = 0.37), and was comparable to CGM+CSII
      ( d = 0.03). CGM+CSII conferred advantage over CSII Alone ( d = 0.34). Clinical
      elevation of distress was associated with not using any technology particularly
      for adolescents. CONCLUSIONS: Technology use is associated with lower adolescent
      distress than lower parent distress. CGM Alone is associated with lower
      adolescent and parent distress than CSII or CGM+CSII. This appears to be
      clinically meaningful based on cut scores for measures. CGM is associated with
      lower A1c independent of being used alone or with CSII.

PMID- 29595062
TI  - Tendoscopic Treatment of Peroneal Intrasheath Subluxation: A New Subgroup With
      Superior Peroneal Retinaculum Injury.
AB  - BACKGROUND: Snapping peroneal tendons is a rare cause of lateral ankle pain. Two
      subgroups have been described: chronic subluxation with superior peroneal
      retinaculum (SPR) injury and intrasheath subluxation with SPR intact. The aim of
      the study was to report the tendoscopic findings and results in patients affected
      by snapping peroneal tendons without evident dislocation. METHODS: Between 2010
      and 2015, a total of 18 patients with a retromalleolar "click" sensation and no
      clinical signs of peroneal tendon dislocation underwent tendoscopy. Mean age was
      29 years (range, 18-47). Mean follow-up was 45 months (range, 18-72). RESULTS:
      Tendoscopic examination revealed an intact SPR in 12 patients. Of these 12, a
      space-occupying lesion was present in 7, a superficial tear of peroneus brevis in
      4, and a shallow fibular groove in 7. An SPR injury without peroneal tendon
      dislocation was observed in the remaining 6 patients. All these 6 patients
      presented a shallow fibular groove. Although the SPR was injured, they had been
      diagnosed as intrasheath subluxation. Patients with intrasheath subluxation and
      intact SPR underwent debridement of a space-occupying lesion in 11 cases and
      fibular groove deepening in 5 cases. Patients with intrasheath subluxation and
      SPR injury underwent fibular groove deepening without addressing the SPR. At
      follow-up, the mean American Orthopaedic Foot & Ankle Society score increased
      from 76 (range, 69-85) preoperatively to 97 (range, 84-100). No recurrence or
      major complications were reported. Conclusion Intrasheath subluxation of peroneal
      tendons was successfully treated tendoscopically. A new subgroup of intrasheath
      subluxation with SPR injury but no clinically evident peroneal tendon dislocation
      is reported. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29595063
TI  - 3-Monochloropropane-1,2-diol (alpha-chlorohydrin) disrupts spermatogenesis and
      causes spermatotoxicity in males of the Egyptian fruit-bat (Rousettus
      aegyptiacus).
AB  - We evaluated the sterilizing effect of 3-monochloropropane-1, 2-diol (3-MCPD) in
      male Egyptian fruit bats (Rousettus aegyptiacus). We used three groups. One was
      treated with 70 mg/kg 3-MCPD for 4 days. The second group was treated with 3-MCPD
      as a bait formulation (known concentration of 3-MCPD mixed with a known amount of
      food). The third group was untreated controls. We compared the weights of the
      reproductive organs, histology of the testes, occurrence of spermatogenesis, and
      the count, motility and abnormalities of epididymal sperm of treated males with
      those of the untreated control group. 3-MCPD caused significantly decreased
      weights of reproductive organs, several testicular histological alterations and
      spermatogenic arrest accompanied by significant decreases in sperm count and
      motility, and significantly increased number of abnormal sperm. 3-MCPD bait was
      readily accepted by the animals. 3-MCPD, even in low doses and after limited
      exposure, disrupted spermatogenesis in males of the Egyptian fruit bat. Our
      findings have potential value for public health and agricultural authorities, and
      for vertebrate pest managers. 3-MCPD may have application for control of this
      pest.

PMID- 29595064
TI  - Accelerating drug development in pediatric cancer: a novel Phase I study design
      of venetoclax in relapsed/refractory malignancies.
AB  - Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for
      some patients previously treated for chronic lymphocytic leukemia, and has shown
      promising activity in adult studies across several hematologic malignancies.
      Preclinical studies have demonstrated venetoclax activity in pediatric patient
      derived xenograft models and cell lines; however, clinical studies in pediatric
      patients have yet to be conducted. The prognosis is poor for children with most
      relapsed/refractory malignancies, and limited treatment options result in unmet
      clinical need. Herein, we describe the rationale and design of the first study of
      venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I
      trial investigating the safety and pharmacokinetics of venetoclax monotherapy
      followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439
      14; NCT03236857).

PMID- 29595065
TI  - Protease inhibitor therapy for hepatitis C virus-infection.
AB  - INTRODUCTION: The hepatitis C virus (HCV) has affected an estimated of 80 million
      individuals worldwide and is a strain on public health. Around 25-30% of patients
      in Europe and the US who are infected with HIV are coinfected with HCV. Prior to
      2013, treatment modalities containing an NS3/4A protease inhibitor in combination
      with pegylated interferon and ribavirin improved sustained virological response
      (SVR) rates. However, rates of severe side effects were high. Nowadays, oral
      direct-acting antiviral (DAA) combination therapy offers excellent treatment
      efficacy, safety and tolerability. Areas covered: This review focuses on the
      current literature and clinical evidence and their impact regarding NS3/4A
      protease inhibitors. The pitfalls encountered in treating HIV- and HBV-coinfected
      patients are also discussed. Expert opinion: In the era of DAA treatment, third
      generation pan-genotypic NS3/4A protease inhibitors (mainly glecaprevir and
      voxilaprevir) show high antiviral activity and a genetic resistance barrier with
      cure rates of over 95% when combined with an NS5A inhibitor, irrespective of
      baseline resistance associated variants (RASs) being present. These new key
      components of DAA combination therapy are impressive options to eradicate HCV in
      the so-called difficult-to-treat population (e.g. compensated cirrhosis, end
      stage renal disease and patients who failed previous DAA treatment).

PMID- 29595066
TI  - Follicular fluid levels of anti-Mullerian hormone, insulin-like growth factor 1
      and leptin in women with fertility disorders.
AB  - : Anti-Mullerian hormone (AMH), insulin-like growth factor 1 (IGF1) and leptin
      are produced in the granulosa cells of follicles and play an important role in
      the growth and maturation of follicles. The aim of our study was to monitor AMH,
      IGF1 and leptin levels in a group of healthy women and compare them to a group of
      women with fertility disorders. The second aim was the evaluation of biomarker
      levels in relation to the identified cause of infertility. Totally, 146 females
      were enrolled into our study. Seventy-two healthy controls and seventy-four
      females with fertility disorders were divided into four subgroups: anovulation,
      endometriosis, fallopian tube damage, unknown reason. IGF1 was the only biomarker
      with significantly lower levels throughout the entire group with fertility
      disorders. We did not identify any statistically significant differences for AMH
      and leptin. Regarding subgroups, significant differences were only observed in
      the group of anovulatory women. AMH and leptin showed higher levels while IGF1
      showed lower levels. In conclusion, levels of AMH, IGF1 and leptin found in
      follicular fluid are sensitive markers for anovulatory fertility disorders. AMH,
      IGF1 and leptin levels in follicular fluid have no relation to the fertility
      disorders caused by endometriosis, fallopian tube damage or disorders with
      unknown etiology. ABBREVIATIONS: AMH: anti-Mullerian hormone; IGF1: insulin-like
      growth factor 1; PCOS: polycystic ovary syndrome.

PMID- 29595067
TI  - N-containing compounds from Periplaneta americana and their activities against
      wound healing.
AB  - Three new compounds, periplanamides A (1) and B (2), periplanpyrazine A (3), a
      new naturally occurring compound salicyluric acid methyl ester (6), and seventeen
      known compounds were isolated from the medicinal insect Periplaneta americana.
      The structures of the new compounds were elucidated on the basis of spectroscopic
      methods. The absolute configurations of 2 were assigned by computational methods.
      Biological activities of these isolates except 1, 9, 11, and 13 toward nitric
      oxide (NO) production, cell proliferation in HDFs, cell migration and
      angiogenesis in HUVECs were evaluated.

PMID- 29595068
TI  - Macrocyclic bis-quinolizidine alkaloids from Xestospongia muta.
AB  - A new stereoisomer Meso-araguspongine C together with nine reported macrocyclic
      bis-quinolizidine alkaloids araguspongines A, C, E, L, N-P, petrosin, and
      petrosin A were isolated from marine sponge Xestospongia muta. Stereochemistry of
      meso-araguspongine C (2) and araguspongines N-P (3-5) were established by their
      NMR data and conformational analyses. Both araguspongine C (1) and meso
      araguspongine C (2) exhibited great cytotoxic activity towards HepG-2, HL-60, LU
      1, MCF-7, and SK-Mel-2 human cancer cells (IC50 in the range of 0.43-1.02 MUM).
      At a concentration of 20 MUM, isolated compounds (1-10) also showed modest
      inhibitory effects (from 7.6 to 40.8%) on the NO production in LPS activated
      RAW264.7 macrophages.

PMID- 29595069
TI  - Sinulaspirolactam A, a novel aza-spirocyclic valerenane sesquiterpenoid from soft
      coral Sinularia sp.
AB  - A novel valerenane sesquiterpenoid sinulaspirolactam A (1), together with five
      known compounds, was isolated from the soft coral Sinularia sp. Their structures
      were determined by spectroscopic analyses. The absolute configuration of 1 was
      established by ECD calculation. Compound 1 was the first example of valerenane
      sesquiterpenoid bearing an aza-spiro[4.5] ring moiety, the plausible biogenetic
      pathway of which was proposed. Cytotoxic activities of these compounds were also
      evaluated.

PMID- 29595070
TI  - The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to
      Cisplatin: A Common Mechanism of Action via Centromere Protein M.
AB  - Although garlic induces apoptosis in cancer cells, it is unclear whether the
      effects are similar to those of cisplatin against bladder cancer (BC). Therefore,
      this study investigated whether garlic extracts and cisplatin show similar
      activity when used to treat BC. The effect of garlic on T24 BC cell line was
      examined in a BALB/C-nude mouse xenograft model and compared with that of
      cisplatin. Tissue microarray analysis and gene network analysis were performed to
      identify differences in gene expression by control tumors and tumors exposed to
      garlic extract or cisplatin. Investigation of gene expression based on tissues
      from 165 BC patients and normal controls was then performed to identify common
      targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin
      (0.05[Formula: see text]mg/kg)- and garlic-treated mice were significantly
      smaller than those in negative control mice. However, cisplatin-treated mice also
      showed a significant reduction in body weight. Microarray analysis of tumor
      tissue identified 515 common anticancer genes in the garlic and cisplatin groups
      ([Formula: see text]). Gene network analysis of 252 of these genes using the
      Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to
      gene networks. BC (NMIBC and MIBC) patients with low expression of centromere
      protein M (CENPM) showed significantly better progression-free survival than
      those with high expression. Garlic extract shows anticancer activity in vivo
      similar to that of cisplatin, with no evident of side effects. Both appear to act
      by targeting protein-DNA complex assembly; in particular, expression of CENPM.

PMID- 29595071
TI  - Total Flavones of Abelmoschus manihot Exhibits Pro-Angiogenic Activity by
      Activating the VEGF-A/VEGFR2-PI3K/Akt Signaling Axis.
AB  - Angiogenesis is a process of new blood vessel formation from pre-existing
      vessels. Vascular endothelial growth factor-A (VEGF-A) binds to VEGF receptor-2
      (VEGFR2) and thus activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway
      play a central role in angiogenesis. Total flavones of Abelmoschus manihot (TFA),
      the major active component of the traditional Chinese herb Abelmoschus manihot,
      display novel pro-angiogenic activity. However, little information concerning its
      underlying mechanism is available. Here we investigate the pro-angiogenesis of
      TFA with the aim of understanding its mechanism of action. Human umbilical vein
      endothelial cells (HUVECs) and the chick chorioallantoic membrane (CAM) model
      were used to evaluate pro-angiogenesis of TFA using cell viability, wounding
      healing, transwell invasion, tube formation, RT-qPCR and Western blot methods.
      LY294002, a PI3K inhibitor, was used to interfere with PI3K/Akt pathway signal
      for assessing the underlying mechanism. Results in vitro indicated TFA obviously
      promoted HUVECs proliferation, migration, invasion and tube formation.
      Furthermore, TFA markedly augmented PI3K and Akt phosphorylation and up-regulated
      VEGF-A and VEGFR2 expression in HUVECs. However, pre-treatment with LY294002 not
      only markedly attenuated TFA-induced cells proliferation, migration, invasion and
      tube formation, but also significantly abolished TFA-induced VEGF-A and VEGFR2
      over-expression as well as PI3K and Akt phosphorylation. Experiments in CAM model
      showed TFA significantly promoted the formation of branched blood vessels and was
      dramatically suppressed by LY294002. Taken together, TFA promoted angiogenesis
      both in vitro and in vivo which, however, were counteracted by LY294002,
      suggesting at least in part, TFA exhibits pro-angiogenic activity by activating
      the VEGF-A/VEGFR2-PI3K/Akt signaling axis.

PMID- 29595072
TI  - Platycodin D Reverses Pathological Cardiac Hypertrophy and Fibrosis in
      Spontaneously Hypertensive Rats.
AB  - Platycodin D (PD) is the main active saponin isolated from Platycodon
      grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti
      inflammation and anti-obesity biological effects. The current study aims to
      evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy
      in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling
      pathway. Significant increases in the cardiac functional indices of left
      ventricular internal diameter end diastole (LVIDd) and left ventricular internal
      diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric
      hypertrophy markers, such as CaMKII[Formula: see text] and calcineurin; and
      expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously
      hypertensive groups. PD treatment reversed these increases in SHRs. In addition,
      an increase in the fibrosis markers FGF2, uPA, MMP2, MMP9, TGF[Formula: see text]
      1 and CTGF during cardiac hypertrophy was detected by western blotting analyses.
      These results demonstrated that PD treatment considerably attenuates cardiac
      fibrosis. Histopathological examination revealed that PD treatment remarkably
      reduced collagen accumulation in contrast to spontaneously hypertensive groups.
      This study clearly suggests that PD provides myocardial protection by alleviating
      two damaging responses to hypertension, fibrosis and hypertrophy, in the heart.

PMID- 29595073
TI  - Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-[Formula: see
      text]B, MAPK and Inflammatory Cytokines.
AB  - Asatone is an active component extracted from the Chinese herb Radix et Rhizoma
      Asari. Our preliminary studies have indicated that asatone has an anti
      inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide
      (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the
      onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS
      induced requires further investigation. In vitro studies revealed that asatone at
      concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically
      prevented cytotoxicity and concentration-dependently reduced NO production in the
      LPS-challenged macrophages. In an in vivo study, the intratracheal administration
      of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell
      counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL
      1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as
      mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone
      could reverse all of these effects. Asatone markedly reduced the levels of TNF
      [Formula: see text] and IL-6 in the lung and liver, but not in the kidney of
      mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula:
      see text]B activations, whereas asatone increased anti-oxidative enzymes in the
      bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung
      tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory
      modalities, including the major anti-inflammatory pathways of NF-[Formula: see
      text]B and mitogen-activated protein kinases. These findings suggest that asatone
      can be applied in the treatment of ALI.

PMID- 29595074
TI  - Alleviation of Hippocampal Endoplasmic Reticulum Stress by Allomyrina dichotoma
      Larvae Extract.
AB  - In the brain, endoplasmic reticulum (ER) stress results in synaptic dysfunction
      and eventually leads to neurodegeneration. Allomyrina dichotoma larvae are a
      Chinese ethnomedicine and are widely used in East Asia. In the present study, we
      investigated the ability of ethanol extract of A. dichotoma larvae (ADE) to
      improve synaptic structure and function by activating unfolded protein response
      (UPR) under ER stress in animal and neuron culture models. ER stress was induced
      in obese mice fed a high fat diet (HFD) or by treating dissociated cultures of
      rat embryonic (E19) hippocampal neurons with tunicamycin (TM). Western blot and
      real-time or conventional RT-PCR were performed to analyze the expressions of ER
      stress marker proteins. In dissociated hippocampal cultures, immunocytochemistry
      was performed for synaptic proteins, and cultures were stained with styryl dye
      FM1-43 to assess presynaptic activities. In HFD-fed obese mice, ADE efficiently
      reduced the expressions of ER stress markers, such as, xbp-1, chop, atf4, erdi4,
      and eIf2a, and those of the ER chaperone/foldases Bip/grp78, Ero-1l, and PDI.
      Unconventionally spliced xbp-1s mRNA was not detected. In primary rat hippocampal
      cultures under ER stress, ADE significantly lowered the nuclear expression of
      CHOP, inhibited the downregulations of postsynaptic proteins, such as, GluN2A,
      GluN2B, and PSD-95, and maintained the pool size of recycling presynaptic
      vesicles. The study shows that ADE potently suppressed the induction of ER stress
      and maintained the structure and function of hippocampal neurons, and suggests
      that ADE is a potentially valuable food supplement and preventive therapeutic for
      ER stress-related nervous disorders.

PMID- 29595075
TI  - Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and
      Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP
      Activating Protein Kinase Pathway.
AB  - The prevalence of metabolic diseases has risen globally in parallel with the
      obesity epidemic over the past few decades. Green tea has been reported to have
      metabolically beneficial effects on obesity; however, the mechanism by which
      green tea regulates lipid metabolism is not clearly understood. Male c57BL/6 mice
      were fed a normal chow diet, a high-fat diet (HFD), or an HFD supplemented with
      various doses of epigallocatechin gallate-rich green tea extract (GTE) for 12
      weeks. GTE supplementation reduced body weight gain, prevented hepatic fat
      accumulation, decreased hypertriglyceridemia, and improved hyperglycemia and
      insulin resistance in HFD-fed mice. The underlying mechanisms of these beneficial
      effects of GTE might involve the upregulation of sirtuin 1 and AMP activated
      protein kinase (AMPK) and the downregulation of enzymes related to de novo
      lipogenesis. Consistent with the in vivo findings, GTE increased the expression
      and activity of sirtuin 1, enhanced the binding of sirtuin 1 to liver kinase B1
      (LKB1) and subsequent deacetylation of LKB1, and reduced triglyceride
      accumulation in HepG2 cells. These results suggest the possible therapeutic
      potential of dietary epigallocatechin gallate-rich GTE supplementation for
      preventing the development and progression of hepatic steatosis and obesity.

PMID- 29595076
TI  - Anti-Apoptotic Mechanisms of Acupuncture in Neurological Diseases: A Review.
AB  - Apoptosis, known as programmed cell death, plays a significant role in the
      pathogenesis of neurological diseases. Most of these diseases can be obviously
      alleviated by means of acupuncture treatment. Current research studies have shown
      that the efficacy of acupuncture to these medical conditions is closely
      associated with the anti-apoptotic potentials. Mainly based on the acupuncture's
      anti-apoptotic efficacy in prevalent neurological disorders, including cerebral
      ischemia-reperfusion injury, Alzheimer's disease, depression or stress related
      modes, spinal cord injuries, etc., this review comes to a conclusion that the
      anti-apoptotic effect of acupuncture treatment for neurological diseases,
      evidently reflected through Bcl-2, Bax or caspase expression change, results from
      regulating mitochondrial or autophagic dysfunction as well as reducing oxidative
      stress and inflammation. The possible mechanisms of acupuncture's anti-apoptotic
      effect are associated with a series of downstream signaling pathways and the up
      regulated expression of neurotrophic factors. It is of great importance to
      illuminate the exact mechanisms of acupuncture treatment for neurological
      dysfunctions.

PMID- 29595078
TI  - Symptom: Cause, Effect, Both, or Neither?

PMID- 29595077
TI  - Hypouricemic Effects of Armillaria mellea on Hyperuricemic Mice Regulated through
      OAT1 and CNT2.
AB  - Ethanol and water extracts of Armillaria mellea were prepared by directly soaking
      A. mellea in ethanol (AME) at 65[Formula: see text]C, followed by decocting the
      remains in water (AMW) at 85[Formula: see text]C. Significantly, AME and AMW at
      30, 60 and 120[Formula: see text]mg/kg exhibited excellent hypouricemic actions,
      causing remarkable declines from hyperuricemic control (351[Formula: see
      text][Formula: see text]mol/L, [Formula: see text]) to 136, 130 and 115[Formula:
      see text][Formula: see text]mol/L and 250, 188 and 152[Formula: see
      text][Formula: see text]mol/L in serum uric acid, correspondingly. In contrast to
      the evident renal toxicity of allopurinol, these preparations showed little
      impacts. Moreover, they showed some inhibitory effect on XOD (xanthine oxidase)
      activity. Compared with hyperuricemic control, protein expressions of OAT1
      (organic anion transporter 1) were significantly elevated in AME- and AMW-treated
      mice. The levels of GLUT9 (glucose transporter 9) expression were significantly
      decreased by AMW. CNT2 (concentrative nucleoside transporter 2), a key target for
      purine absorption in gastrointestinal tract was involved in this study, and was
      verified for its innovative role. Both AME and AMW down-regulated CNT2 proteins
      in the gastrointestinal tract in hyperuricemic mice. As they exhibited
      considerable inhibitory effects on XOD, we selected XOD as the target for virtual
      screening by using molecular docking, and four compounds were hit with high
      ranks. From the analysis, we concluded that hydrogen bond, Pi-Pi and Pi-sigma
      interactions might play important roles for their orientations and locations in
      XOD inhibition.

PMID- 29595079
TI  - Universal and culturally specific aspects of sensitive responsiveness to young
      children.
AB  - This article describes the earliest processes involved in socializing infants
      into cultural beings, that are thought to set the stage for the type of
      interactions described in this special issue. From birth onwards, infants
      experience and learn whether their signals will be answered, and in what way, by
      whom, and when. Infants learn about their own culture from the persons around
      them through the meaning and interpretations these persons give to their
      behaviors. Many questions remain about how these processes link to infant brain
      development, and how insights from cultural and biological anthropology can be
      used to elucidate the meaning and function of sensitive caregiver-infant
      interactions.

PMID- 29595080
TI  - Characterization of integrons, extended-spectrum beta-lactamases, AmpC
      cephalosporinase, quinolone resistance, and molecular typing of Shigella spp.
      from Iran.
AB  - INTRODUCTION: The wide distribution of extended-spectrum beta-lactamase (ESBL)
      producing Shigella spp., along with the emergence of fluoroquinolone resistant
      isolates, is a serious threat to public health, posing a new challenge for the
      effective treatment of shigellosis. The purpose of this study was to determine
      the level of antimicrobial resistance, the presence of genes encoding resistance
      to cephalosporins, and plasmid-mediated quinolone resistance (PMQR) among the
      clinical isolates of Shigella spp. in Iran. MATERIALS AND METHODS: A total of 142
      Shigella isolates were collected from different parts of Iran. All of the
      cephalosporin resistant Shigella strains were selected based on ESBL and AmpC
      production. The presence of PMQR regions was assessed in ciprofloxacin-resistant
      isolates, and genetic relatedness in the isolates was determined. RESULTS:
      Seventy-eight Shigella isolates were found to be resistant to extended-spectrum
      cephalosporin (ESC). The blaCTX-M15 was the most prevalent cephalosporinase. Four
      ESBL-producing isolates were also resistant to ciprofloxacin. Among the PMQR
      regions, aac(6')-lb-cr gene was the most prevalent, as it was seen in 83.3% of
      the ciprofloxacin resistant isolates, while qnrA was positive in 16.7%. Clonal
      relatedness showed a limited variety of clones was responsible for Shigella
      infection in the region studied. CONCLUSION: Overall, our findings indicated that
      a large number of ESBL producing Shigella spp. were mediated mainly by blaCTX
      M15. This study is the first report on ciprofloxacin-resistant ESBL-producing
      Shigella isolates from patients in Iran.

PMID- 29595081
TI  - Hip thrust-based PAP effects on sprint performance of soccer players: heavy
      loaded versus optimum-power development protocols.
AB  - This study aimed to investigate the acute effects of two barbell hip thrust-based
      post-activation potentiation (PAP) protocols on subsequent sprint performance.
      Using a crossover design, eighteen soccer athletes performed 5 m, 10 m, and 20 m
      sprints before and 15 s, 4 min, and 8 min after two PAP protocols. The PAP
      conditioning activities consisted of hip thrust exercises loaded with either 85%
      1RM or a load for optimum power development. The resulting 5 m and 10 m sprint
      performances were impaired at 15 s following both protocols. At 4 min and 8 min,
      meaningful improvements were observed for the three sprint distances following
      both of the protocols. Meaningful differences were found when comparing the two
      PAPs over time: greater impairments in 5 m and 10 m following the 85% of 1 RM
      protocol after 15 s, and greater improvements in all sprint distances after 4 min
      and 8 min following the optimum power development protocol. Positive correlations
      between the hip thrust's 1RM and power values and the overall individual PAP
      responses were found. This investigation showed that both heavy-loaded and
      optimum-power hip thrust exercises can induce a PAP response, with the optimum
      power development protocol preferred due its higher efficiency.

PMID- 29595082
TI  - A Case Report of Drug-Eluting Balloon as a New Treatment Option for Cardiac
      Allograft Vasculopathy.

PMID- 29595083
TI  - Playing surface and UK professional rugby union injury risk.
AB  - Artificial rugby union playing surface installation is increasing. This
      prospective cohort study aimed to examine the effect of playing surface on match
      injury types within 157 players of two UK professional rugby union clubs playing
      209 matches (96 on artificial surfaces and 113 on grass) over three seasons.
      There was no difference in overall injury risk between the two playing surfaces
      with injury incidence on artificial 80.2 (CI 69.9-91.7) and on grass 81.9 per
      1000 match-hours (CI 72.2-92.5), with an incidence rate ratio (RR) of 0.98 (CI
      0.82-1.17). There was a higher rate of concussion (RR 0.52, CI 0.34 - 0.78) and
      chest injuries on grass (RR 0.26 CI 0.07, 0.95), and a higher rate of thigh
      haematoma (RR 2.25, CI 1.05-4.82) foot injuries (RR 4.12, CI 1.10, 15.40) and
      injury to players being tackled (RR 1.46, CI 1.00, 2.15) on artificial. Whilst
      there was no higher injury risk for matches played on artificial versus natural
      grass surfaces, the higher incidence of concussion and chest injury on grass, and
      the higher rate of foot injuries on artificial surfaces may be related to tackle
      and footwear-to-surface interface factors.

PMID- 29595084
TI  - A Tomato Nucleotide Binding Sites-Leucine-Rich Repeat Gene Is Positively Involved
      in Plant Resistance to Phytophthora infestans.
AB  - The nucleotide binding sites-leucine-rich repeat (NBS-LRR) genes are key
      regulatory components of plant to pathogens. Phytophthora infestans-inducible
      coding sequence encoding an NBS-LRR (SpNBS-LRR) protein in tomato (Solanum
      pimpinellifolium L3708) was cloned and characterized based on our RNA-Seq data
      and tomato genome. After sequence analysis, SpNBS-LRR was identified as a
      hydrophilic protein with no transmembrane topological structure and no signal
      peptide. SpNBS-LRR had a close genetic relationship to RPS2 of Arabidopsis
      thaliana by phylogenetic analysis. In addition, SpNBS-LRR gene was mainly
      expressed in root, with low expression observed in leaf and stem. To further
      investigate the role of SpNBS-LRR in tomato-P. infestans interaction, SpNBS-LRR
      was introduced in susceptible tomatoes and three transgenic lines with higher
      expression level of SpNBS-LRR were selected. These transgenic tomato plants that
      overexpressed SpNBS-LRR displayed greater resistance than wild-type tomato plants
      after infection with P. infestans, as shown by decreased disease index, lesion
      diameters, number of necrotic cells, P. infestans abundance, and higher
      expression levels of the defense-related genes. This information provides insight
      into SpNBS-LRR involved in the resistance of tomato to P. infestans infection and
      candidate for breeding to enhance biotic stress-resistance in tomato.

PMID- 29595085
TI  - Immunosuppressive and antiviral treatment of hepatitis C virus-associated
      glomerular disease: A long-term follow-up.
AB  - BACKGROUND: The evidence in the medical literature on the treatment of hepatitis
      C virus-associated glomerular disease is extremely limited. The advent of
      nonconventional immunosuppressive agents and direct-acting antivirals promises
      high efficacy and safety. AIMS: We conducted an open-label, single-arm clinical
      study to examine the efficacy and safety of a combined approach for hepatitis C
      virus-associated glomerular disease. METHODS: In the first phase of the study,
      patients with hepatitis C virus-associated glomerular disease received interferon
      based antiviral therapy and immunosuppressive agents; since 2013, interferon-free
      antiviral therapy was adopted and novel immunosuppressants (including B-cell
      depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were
      choiced. Virological and clinical responses were evaluated over a long
      observation period (median follow-up of 60 weeks and 46.5 months after the end of
      treatment with interferon and direct-acting antiviral agents, respectively).
      RESULTS: We enrolled 25 consecutive patients with hepatitis C virus-associated
      glomerular disease, 8 being liver transplant recipients for hepatitis C. A total
      of 13 patients received therapy with direct-acting antivirals and experienced
      sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after
      treatment ended, sustained viral response12). The mean (+/-standard deviation)
      proteinuria decreased from 2.61 +/- 1.01 at baseline to 1.71 +/- 1.43 (g/day) at
      sustained viral response 48, p = 0.031; microscopic hematuria and serum
      cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively,
      after sustained viral response by direct-acting antivirals. Adverse events
      occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin
      related anemia requiring blood transfusions (no drop-outs). After sustained viral
      response by direct-acting antivirals, immunosuppressive and immunomodulatory
      agents were initiated in clinical relapsers ( n = 2) and nonresponders ( n = 3)
      with some benefit. Among patients on interferon-based regimens ( n = 12), viral
      response (sustained viral response 24) and dropout rates were 58% (7/12) and 33%
      (4/12), respectively. After sustained viral response by interferon-based therapy,
      clinical relapsers ( n = 3) were successfully managed with immunosuppressive
      agents in two patients. CONCLUSION: Treatment with direct-acting antivirals
      provides excellent rates of viral response and safety in patients with hepatitis
      C virus-related glomerular disease; viral response was frequently accompanied by
      clinical improvement. The absence of hepatitis C virus RNA from serum allowed
      immunosuppressive and immunomodulatory therapies with benefits for glomerular
      abnormalities and no concern on hepatitis C virus replication.

PMID- 29595086
TI  - Impact of multi- versus single finger proximal interphalangeal joint
      arthroplasty: analysis of 249 fingers treated in 15 years.
AB  - : We retrospectively reviewed and compared the outcomes and complications
      associated with 81 single digit and 168 multi-digit proximal interphalangeal
      joint arthroplasties performed from 1998 to 2012 in 136 patients. Clinical
      outcomes were assessed with an average follow-up of 5.3 years for single digit
      and 5.9 years for multi-digit proximal interphalangeal joint arthroplasty.
      Comparing single versus multi-digit proximal interphalangeal joint arthroplasty,
      the reoperation-free survival was 67% and 68% at 5 years and 56% and 67% at 10
      years, respectively. Furthermore, in comparison of single versus multi-digit
      proximal interphalangeal joint arthroplasty, the revision-free survival was 80%
      and 86% at 5 years and 80% and 85% at 10 years, respectively. Given the similar,
      or even slightly improved, rates of complications, reoperation, and revision
      surgery, proximal interphalangeal joint arthroplasty performed on multi-digits
      results in no worse outcomes compared with single digit proximal interphalangeal
      joint arthroplasty. LEVEL OF EVIDENCE: IV.

PMID- 29595087
TI  - Group B streptococci cultured in urine during pregnancy associated with preterm
      delivery: a selection problem?
AB  - OBJECTIVE: To investigate an association between Group B streptococci (GBS) in
      urine culture during pregnancy and preterm delivery. METHODS: A population-based
      cohort consisted of all the pregnant women (n = 36,097) from the catchment area
      of Lillebaelt Hospital, Denmark, during the period January 2002 -December 2012.
      The cohort of 34,285 singleton pregnancies used in this study was divided into
      three groups. Group I (N = 249) included women whose urine culture was positive
      for GBS; group II (N = 5765) included women whose urine culture was negative for
      GBS; and group III (N = 28 271) included women whose urine had not been cultured
      during pregnancy. Primary outcome was preterm delivery before 37 weeks' gestation
      (PTD). RESULTS: We did not find an association between PTD and GBS bacteriuria in
      the cultured groups (odds ratios (OR) = 0.89; 95% CI: 0.5-1.4) ( Table 1 ). After
      controlling for potential confounders, the PTD remained not associated with GBS
      bacteriuria (adjusted OR = 0.99; 95% CI: 0.6-1.6). Combined, the cultured groups
      (I and II) were associated with a statistically significant higher risk for PTD,
      when compared with the group with no urine specimens taken for culture (OR =
      1.96; 95% CI: 1.8-2.2 and adjusted or 1.80; 95% CI 1.6-2.0). The cultured group
      of women differed considerably from the group of women with no urine specimens
      taken for culture on the vast majority of variables examined. CONCLUSIONS: No
      association between asymptomatic GBS bacteriuria and preterm delivery among women
      with singleton pregnancy and urine specimens cultured during pregnancy was found.
      Previous suggestions of such association may have been compromised by a selection
      problem for testing due to a high-risk profile of pregnancy complications in
      pregnant women selected for urine culture.

PMID- 29595088
TI  - The impacts of rest breaks and stretching exercises on lower back pain among
      commercial truck drivers in Iran.
AB  - PURPOSE: This study aimed to determine the impacts of rest breaks and stretching
      exercises on lower back pain (LBP) in commercial truck drivers. METHODS: This
      quasi-experiment was carried out on 92 truck drivers suffering from chronic LBP.
      Subjects were categorized into three groups (stretching exercises and rest
      breaks, rest breaks only and reference). Pain severity and related disability
      were measured at the beginning of the survey and after 6 and 12 weeks. The latter
      was assessed using the Oswestry low back pain disability questionnaire (OLBPDQ)
      and the Roland Morris questionnaire (RMQ). RESULTS: At the end of the
      intervention, the mean pain scores in the three groups were 2.72 +/- 1.44, 4.11
      +/- 0.86 and 4.90 +/- 1.31 respectively (p < 0.001). The OLBPDQ scores in group 1
      (stretches and resting time breaks) were significantly lower than those in group
      2 (rest break) (p = 0.009). The RMQ scores showed a significant reduction in
      group 1 compared with the other two groups (p = 0.001). Drivers in group 2
      improved more significantly than those in group 3 regarding visual analog scale
      pain score (p = 0.049), OLBPDQ score (p = 0.024) and RMQ score (p = 0.011).
      CONCLUSION: This study provided converging results that supplementary exercises
      during break periods consistently help to minimize LBP and disability.

PMID- 29595089
TI  - Mistaken identity of an open reading frame proposed for PCR-based identification
      of Mycoplasma bovis and the effect of polymorphisms and insertions on assay
      performance.
AB  - Mycoplasma bovis is an important cause of disease in cattle and bison. Because
      the bacterium requires specialized growth conditions, many diagnostic
      laboratories routinely use PCR to replace or complement conventional isolation
      and identification methods. A frequently used target of such assays is the uvrC
      gene, which has been shown to be highly conserved among isolates. We discovered
      that a previously described PCR putatively targeting the uvrC gene amplifies a
      fragment from an adjacent gene predicted to encode a lipoprotein. Comparison of
      the lipoprotein gene sequence from 211 isolates revealed several single
      nucleotide polymorphisms, 1 of which falls within a primer-binding sequence.
      Additionally, 3 isolates from this group were found to have a 1,658-bp
      transposase gene insertion within the amplified region that leads to a false
      negative result. The insertion was not detected in a further 164 isolates. We
      found no evidence that the nucleotide substitution within the primer-binding
      region affects the assay sensitivity, performance, or limit of detection.
      Nonetheless, laboratories utilizing this method for identification of M. bovis
      should be aware that the region amplified may be prone to nucleotide
      substitutions and/or insertions relative to the sequence used for its design and
      that occasional false-negative results may be obtained.

PMID- 29595090
TI  - A post-infection serologic assessment of cattle herd immune status after a
      vesicular stomatitis outbreak and the agreement of antibody assays.
AB  - Vesicular stomatitis (VS) is a vesicular disease of horses, cattle, and pigs in
      the Western Hemisphere caused by viruses in the genus Vesiculovirus. Disease
      manifests as vesicles and erosions on the oral mucosa, teats, prepuce, and
      coronary band, and is similar in presentation to foot-and-mouth disease.
      Laboratory confirmation is therefore required. Conventional assays include
      competitive (c)ELISA and complement fixation (CF). The cELISA provides more
      accurate herd-level detection of VSV-exposed cattle, but may lack the ability to
      capture fluctuating antibody levels in individual animals. The CF assay can
      confirm newly infected animals because of its ability to detect antigen-antibody
      complexes, thus is considered to be indicative of IgM. We evaluated the immune
      status of 2 herds affected by VSV in 2014 by testing sera collected in June 2015.
      Two conventional assays were compared to a novel IgM-IgG ELISA. When sampled in
      2015, both herds had detectable VSV-specific antibodies; 18% and 36% of animals
      tested by cELISA and 2% and 8% of animals tested by CF were positive. The novel
      IgM-IgG assay exhibited fair agreement (adjusted kappa score of 48) with the
      conventional assays, and should be evaluated further to assess its ability to
      replace the 2 separate assays with a single assay system, or for its ability to
      replace the CF assay as a more sensitive method for defining newly exposed
      animals.

PMID- 29595091
TI  - Neuroprotective effect of tempeh against lipopolysaccharide-induced damage in BV
      2 microglial cells.
AB  - OBJECTIVES: This study evaluated the bioactive composition of tempeh products and
      examined the effects of tempeh on BV-2 microglial cell cytotoxicity, neurotrophic
      effects, and expression of inflammatory genes. METHODS: Tempeh products included
      soybean fermented by Rhizopus, soybean fermented through cocultivation with
      Rhizopus and Lactobacillus, and red bean fermented through cocultivation with
      Rhizopus and Lactobacillus (RT-C). We analyzed the bioactive contents of tempeh
      extracts and evaluated the effects of tempeh water extract on lipopolysaccharide
      (LPS)-treated BV-2 cells. RESULTS: The results showed that RT-C water extract had
      the highest concentrations of gamma-aminobutyric acid (GABA) and anthocyanin. The
      tempeh water extracts, especially RT-C, reduced the formation of LPS-induced
      reactive oxygen species, downregulated the levels of nitric oxide synthase and
      phospho-cyclic-AMP response element-binding protein, and upregulated the
      expression of brain-derived neurotrophic factor (BDNF). DISCUSSION: Our data
      demonstrate that RT-C has the highest concentrations of GABA and anthocyanin,
      more effectively reduces oxidative stress and inflammation, and increases the
      expression of BDNF in LPS-induced BV-2 cells.

PMID- 29595092
TI  - Comparative safety evaluation of riot control agents of synthetic and natural
      origin.
AB  - Riot control agents (RCA) are lachrymatory, irritating compounds which
      temporarily incapacitate the uncontainable crowd. Ortho-Chlorobenzylidene
      malononitrile (CS), 2-chloroacetophenone (CN), dibenz[b,f]1:4-oxazepine (CR), and
      nonivamide (PAVA) are synthetic RCAs, while oleoresin extract of chili known as
      oleoresin capsicum (OC) a natural irritant has been in use by various law
      enforcement agencies. Though efficacy of these agents is beyond doubt, they
      suffer from certain drawbacks including toxicity, production cost, and ecological
      compatibility. Presently, we have evaluated the safety of CR, OC, and PAVA on
      inhalation variables along with oral lethality. Additionally, the liver function
      test (LFT) in serum and lungs function was evaluated in broncho-alveolar-lavage
      fluid (BALF), both collected on the 14th day after RCA exposure. Animals then
      sacrificed and histopathology of liver and lungs was carried out. Results showed
      OC and PAVA to be more toxic than CR with an oral LD50 of 150 and 200 mg/kg body
      weight, respectively, while CR was safe at >3 g/kg body weight. All three agents
      caused severe impairment of respiratory variables bringing down normal
      respiration by >80% with rise in sensory irritation. Recovery from the irritating
      effect of CR was more rapid than OC and PAVA. LFT and BALF variables were not
      significantly different from that of control. There were no remarkable
      histopathological changes in liver and lungs. Hence, as per results, CR is safest
      among all synthetic and natural origin RCAs and can be safely used for effective
      dispersion of disobedient mob.

PMID- 29595093
TI  - Synergy of clavine alkaloid 'chanoclavine' with tetracycline against multi-drug
      resistant E. coli.
AB  - The emergence of multi drug resistance (MDR) in Gram-negative bacteria (GNB) and
      lack of novel classes of antibacterial agents have raised an immediate need to
      identify antibacterial agents, which can reverse the phenomenon of MDR. The
      purpose of present study was to evaluate synergy potential and understanding the
      drug resistance reversal mechanism of chanoclavine isolated from Ipomoea muricata
      against the multi-drug-resistant clinical isolate of Escherichia coli (MDREC).
      Although chanoclavine did not show antibacterial activity of its own, but in
      combination, it could reduce the minimum inhibitory concentration (MIC) of
      tetracycline (TET) up to 16-folds. Chanoclavine was found to inhibit the efflux
      pumps which seem to be ATPase-dependent. In real-time expression analysis,
      chanoclavine showed down-regulation of different efflux pump genes and decreased
      the mutation prevention concentration of tetracycline. Further, in silico docking
      studies revealed significant binding affinity of chanoclavine with different
      proteins known to be involved in drug resistance. In in silico ADME/toxicity
      studies, chanoclavine was found safe with good intestinal absorption, aqueous
      solubility, medium blood-brain barrier (BBB), no CYP 2D6 inhibition, no
      hepatotoxicity, no skin irritancy, and non-mutagenic indicating towards drug
      likeliness of this molecule. Based on these observations, it is hypothesized that
      chanoclavine might be inhibiting the efflux of tetracycline from MDREC and thus
      enabling the more availability of tetracycline inside the cell for its action.

PMID- 29595094
TI  - Paediatric HIV-1 infection: updated strategies of prevention mother-to-child
      transmission.
AB  - INTRODUCTION: HIV-1 epidemiology is changing and prevention of mother-to-child
      transmission (PMTCT) strategies have been continuously optimized over time.
      However, the correct management of infected women during pregnancy is crucial for
      PMTCT and cases of vertical transmission continue to occur. OBJECTIVE: To review
      the most recent evidence regarding the prevention of MTCT in resource-rich and
      resource-limited settings, focalizing on new possible approaches. RESULTS: New
      issues regard the optimal antiretroviral therapy regimen for pregnant women with
      good immunological control, the use of intrapartum zidovudine (ZDV) in pregnant
      women with low viral load, the optimization of prophylaxis in the settings where
      breastfeeding is recommended and use of combined neonatal prophylaxis (CNP) in
      infants at high-risk for MTCT. Complete viral control, in recent years, has been
      achieved in most infected pregnant women, has led to change the recommended mode
      of delivery, since vaginal birth has become a safe option and is now largely
      recommended. Recent data reported a large use of CNP in preterm infants: this
      practice may be dangerous, due to the lack of safety data, and its efficacy and
      effectiveness is unproven. CONCLUSION: Data are accumulating on efficacy,
      effectiveness and safety of different PMTCT strategies in various possible
      clinical scenarios, however further researches are needed in order to optimize
      the management of infants at extremely low risk for MTCT as well as in those
      presenting with high risk for infection.

PMID- 29595095
TI  - Hospital networks: how to make them work in Belgium? Facilitators and barriers of
      different governance models.
AB  - Objectives This study aims to identify the facilitators and barriers to
      governance models of hospital collaborations. The country-specific
      characteristics of the Belgian healthcare system and legislation are taken into
      account. Methods A case study was carried out in six Belgian hospital
      collaborations. Different types of governance models were selected: two health
      systems, two participant-governed networks, and two lead-organization-governed
      networks. Within these collaborations, 43 people were interviewed. Results All
      structures have both advantages and disadvantages. It is important that the
      governance model fits the network. However, structural, procedural, and
      especially contextual factors also affect the collaborations, such as alignment
      of hospitals' and professionals' goals, competition, distance, level of
      integrated care, time needed for decision-making, and legal and financial
      incentives. Conclusion The fit between the governance model and the collaboration
      can facilitate the functioning of a collaboration. The main barriers we
      identified are contextual factors. The Belgian government needs to play a major
      role in facilitating collaboration.

PMID- 29595096
TI  - Modifying factors of the health belief model associated with missed clinic
      appointments among individuals with sickle cell disease.
AB  - OBJECTIVES: Outpatient care is critical in the management of chronic diseases,
      including sickle cell disease (SCD). Risk factors for poor adherence with clinic
      appointments in SCD are poorly defined. This exploratory study evaluated
      associations between modifying variables from the Health Belief Model and missed
      appointments. METHODS: We surveyed adults with SCD (n = 211) and caregivers of
      children with SCD (n = 331) between October 2014 and March 2016 in six centres
      across the U.S. The survey tool utilized the framework of the Health Belief
      Model, and included: social determinants, psychosocial variables, social support,
      health literacy and spirituality. RESULTS: A majority of adults (87%) and
      caregivers of children (65%) reported they missed a clinic appointment. Children
      (as reported by caregivers) were less likely to miss appointments than adults
      (OR:0.22; 95% CI:(0.13,0.39)). In adults, financial insecurity (OR:4.49; 95%
      CI:(1.20, 20.7)), health literacy (OR:4.64; 95% CI:(1.33, 16.15)), and age
      (OR:0.95; 95% CI:(0.91,0.99)) were significantly associated with missed
      appointments. In all participants, lower spirituality was associated with missed
      appointments (OR:1.83; 95%CI:(1.13, 2.94)). The most common reason for missing an
      appointment was forgetfulness (adults: 31%, children: 26%). A majority thought
      reminders would help (adults: 83%, children: 71%) using phone calls (adults: 62%,
      children: 61%) or text messages (adults: 56%, children: 51%). CONCLUSIONS: Our
      findings demonstrate that modifying components of the Health Belief Model,
      including age, financial security, health literacy, spirituality, and lacking
      cues to action like reminders, are important in missed appointments and
      addressing these factors could improve appointment-keeping for adults and
      children with SCD.

PMID- 29595097
TI  - The effect of nurses' empowerment perceptions on job safety behaviours: a
      research study in Turkey.
AB  - OBJECTIVE: This study aimed to investigate the effect of nurses' empowerment
      perceptions on job safety behaviours. METHODS: A survey of 377 nurses working in
      five hospitals in Turkey was conducted using the conditions of work effectiveness
      questionnaire, psychological empowerment instrument, universal precautions
      compliance scale and occupational health and safety obligations compliance scale.
      Relations between variables were tested using Pearson's correlation and path
      analysis. RESULTS: There was a moderate and statistically significant
      relationship between psychological and structural empowerment and complying with
      universal safety measures and meeting occupational health and safety obligations.
      Also, an increase of 1 unit on the level of psychological empowerment was found
      to correspond to an increase of 0.37 units on the level of universal precautions
      compliance and to an increase of 0.46 units on the level of occupational health
      and safety obligations compliance. As such, an increase of 1 unit in structural
      empowerment corresponds to an increase of 0.53 units on the level of universal
      precautions compliance and to an increase of 0.36 units (total effect) on the
      level of occupational health and safety obligations compliance. CONCLUSIONS: The
      findings reveal that empowerment is a valuable tool for nurses' positive job
      safety behaviours.

PMID- 29595100
TI  - The EU Circular Economy Package: A genius programme or an old hat?

PMID- 29595099
TI  - Fluidized bed combustion bottom ash: A better and alternative geo-material
      resource for construction.
AB  - Though the majority of research on fly ash has proved its worth as a construction
      material, the utility of bottom ash is yet questionable due to its generation
      during the pulverized combustion process. The bottom ash produced during the
      fluidized bed combustion (FBC) process is attracting more attention due to the
      novelty of coal combustion technology. But, to establish its suitability as
      construction material, it is necessary to characterize it thoroughly with respect
      to the geotechnical as well as mineralogical points of view. For fulfilling these
      objectives, the present study mainly aims at characterizing the FBC bottom ash
      and its comparison with pulverized coal combustion (PCC) bottom ash, collected
      from the same origin of coal. Suitability of FBC bottom ash as a dike filter
      material in contrast to PCC bottom ash in replacing traditional filter material
      such as sand was also studied. The suitability criteria for utilization of both
      bottom ash and river sand as filter material on pond ash as a base material were
      evaluated, and both river sand and FBC bottom ash were found to be satisfactory.
      The study shows that FBC bottom ash is a better geo-material than PCC bottom ash,
      and it could be highly recommended as an alternative suitable filter material for
      constructing ash dikes in place of conventional sand.

PMID- 29595101
TI  - Orthopedic Aspects of the Diabetic Foot.
AB  - BACKGROUND: Diabetes Mellitus (DM) is a common medical condition affecting more
      than 6% of the world population. Besides well-known pathology like diabetic
      retinopathy and renal insufficiency, it carries important orthopedic
      implications, especially around the foot and ankle (diabetic foot). Focus: This
      article focusses on the three major areas confronting the orthopedist: 1) changes
      in foot statics and biology leading to ulceration with or without osteomyelitis,
      2) ankle fractures, particularly complications after a fracture and 3) Charcot
      foot. Their pathophysiology, clinical features, classification, diagnostic
      dilemmas and treatment options are discussed. CONCLUSION: DM is very common and
      is often associated with foot problems. Diabetic foot is a special condition that
      needs special attention. This article aims to provide the necessary knowledge to
      a better understanding and treatment of the diabetic foot.

PMID- 29595102
TI  - Pasireotide - Mechanism of Action and Clinical Applications.
AB  - BACKGROUND: Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue
      (SSA) developed as the successor of the first-generation SSAs. Currently,
      pasireotide is recommended for the treatment of patients with Cushing's disease
      in whom surgery was unsuccessful, and patients with acromegaly who either remain
      uncontrolled after surgical therapy or in whom tumor resection is not possible.
      METHODS AND RESULTS: Phase II and III clinical trials have shown pasireotide
      efficacy in these diseases, with a similar rate of adverse events when compared
      with first-line SSA, although higher incidence of hyperglycemia has been
      observed. CONCLUSION: Pasireotide therapy provides biochemical control, tumor
      volume reduction, and improves the quality of life in patients with those
      disorders. Furthermore, pasireotide might be considered as second-line therapy in
      patients with metastatic neuroendocrine tumors, and it also might be effective in
      other neoplasms with a high expression of somatostatin receptors. In addition,
      therapy with this novel agent has been effective in prevention of postoperative
      complications after pancreatectomy. However, considering the diversified
      responsiveness to this drug in vivo, future studies should identify factors
      predicting better clinical response to pasireotide.

PMID- 29595103
TI  - Application of Medicinal Plants as a Source for Therapeutic Agents Against
      Streptococcus pyogenes Infections.
AB  - BACKGROUND: Streptococcus pyogenes, a major human pathogen, causes a wide variety
      of invasive systemic infections such as acute pharyngitis, skin and soft-tissue
      infections, especially necrotizing fasciitis. OBJECTIVE: This review focuses on
      the properties of pathogenicity of S. pyogenes and outlines ways to combat
      infection caused by these bacteria through alternative plant-based medicine.
      CONCLUSION: This Gram positive bacterium has an ability to form mature biofilm
      and this sessile life style plays an important role in S. pyogenes pathogenicity.
      The virulence of these bacteria is further strengthened by its ability to
      communicate within the micro-colonies through quorum sensing. Most treatments are
      now aimed at either elimination of this bacterium or suppression of its
      virulence. The emergence of antibiotic resistance among S. pyogenes and treatment
      failure has become an added concern globally. One of its virulence properties,
      biofilm formation, has made it more resistant to antibiotic therapy. This has
      vitalized the necessity for searching alternative therapies for its treatment.
      The growing research in herbal medicines has led to the discovery of various
      phytochemicals to limit the virulence of S. pyogenes.

PMID- 29595104
TI  - Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent
      Deductions?
AB  - BACKGROUND: Metronidazole (MTZ) is a synthetic derivative of nitroimidazole that
      has been widely used for the treatment of several bacterial and parasitic
      infections including trichomoniasis, amoebiasis, giardiasis, liver abscess,
      gingivitis, syphilis and phagedena. Scientists have evaluated its carcinogenicity
      in preclinical in vitro and in vivo studies. METHOD: Google scholar and Pubmed
      search engines were used to construct historic timeline after discovery of MTZ
      with a journey of ~3 decades of research. Similar search was conducted for its in
      vivo carcinogenic activities, further extended to elaborate its role in
      carcinogenicity in humans. RESULTS: In addition to preclinical in vitro
      validation of DNA damage, MTZ has been reported to induce cancer in a variety of
      animal models including lung cancer, malignant lymphomas, breast cancer,
      hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine
      cancer. Several retrospective cohort studies have reported MTZ as a potential
      risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer
      (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the
      reported data have confirmed MTZ carcinogenicity in animals; however it is still
      controversial in humans. Based on previous observations, the oxidative
      metabolites from MTZ are shown to have more carcinogenic effects than the parent
      drug itself. CONCLUSION: Due to potent carcinogenic behaviour, use of MTZ for
      animals' treatment and its uses in animal food products is prohibited in USA and
      European countries; however its clinical use in human population is still
      increasing. Therefore, regular research studies are required to explicate its
      mechanism/s involved in carcinogenesis.

PMID- 29595105
TI  - Derivation of Continuum Models from An Agent-based Cancer Model: Optimization and
      Sensitivity Analysis.
AB  - BACKGROUND: Agent-based models provide a formidable tool for exploring complex
      and emergent behaviour of biological systems as well as accurate results but with
      the drawback of needing a lot of computational power and time for subsequent
      analysis. On the other hand, equation-based models can more easily be used for
      complex analysis in a much shorter timescale. METHODS & OBJECTIVE: This paper
      formulates an ordinary differential equations and stochastic differential
      equations model to capture the behaviour of an existing agent-based model of
      tumour cell reprogramming and applies it to optimization of possible treatment as
      well as dosage sensitivity analysis. RESULTS: For certain values of the parameter
      space a close match between the equation-based and agent-based models is
      achieved. The need for division of labour between the two approaches is explored.

PMID- 29595106
TI  - Isolating Bacteria from Sponges: Why and How?
AB  - BACKGROUND: It is known that sponge-associated bacteria are an attractive source
      of new bioactive substances with biotechnological potential. These include
      antimicrobials, enzymes and surfactants. However, the potential of these
      microorganisms remains little investigated due to the difficulty of isolating new
      bacterial groups that produce original bioactive metabolites and enzymes.
      METHODS: Cultivation methods are still playing crucial functions in many studies
      involving bacteria isolated from sponges, and in the traditional approach for
      biodiscovery by screening culture collections. RESULTS: For instance, culture
      media which are rich in nutrients favor the fast cultivation in comparison with
      slower growing bacteria, and diluted and/or poor culture media increase the
      possibility of growing previously uncultured bacteria. The ability to grow
      bacteria in culture and to characterize their secondary metabolites is a crucial
      approach to new biotechnology products of potential value. Many microbial
      biotechnology compounds used nowadays were extracted from cultured bacteria.
      CONCLUSION: This review presents and discusses some strategies to isolate and
      culture bacteria from sponges for biotechnological exploration. Finally, whole
      genome sequencing of sponge-associated bacteria is proposed as a novel strategy
      for biodiscovery.

PMID- 29595107
TI  - Gene and process level modulation to overcome the bottlenecks of recombinant
      proteins expression in Pichia pastoris.
AB  - BACKGROUND: Process development involving system metabolic engineering and
      bioprocess engineering has become one of the major thrust for the development of
      therapeutic proteins or enzymes. Pichia pastoris has emerged as a prominent host
      for the production of therapeutic protein or enzymes. Regardless of producing
      high protein titers, various cellular and process level bottlenecks restrict the
      expression of recombinant proteins in P. pastoris. RESULT AND CONCLUSION: In the
      present review, we have summarized the recent developments in the expression of
      foreign proteins in P. pastoris. Further, we have discussed various cellular
      engineering strategies which include codon optimization, pathway engineering,
      signal peptide processing, development of protease deficient strain and glyco
      engineered strains for the high yield protein secretion of recombinant protein.
      Bioprocess development of recombinant proteins in large-scale bioreactor
      including medium optimization, optimum feeding strategy and co-substrate feeding
      in fed-batch as well as continuous cultivation have been described. The recent
      advances in system and synthetic biology studies including metabolic flux
      analysis in understanding the phenotypic characteristics of recombinant Pichia
      and genome editing with CRISPR-CAS system have also been summarized.

PMID- 29595108
TI  - Synthesis Under Microwave Irradiation And Molecular Docking Of Some Novel
      Bioactive Thiadiazoles.
AB  - A novel series of fused imidazole were prepared from reaction of 2-bromoacetyl-3
      phenyl-1,3,4-thiadiazole with various heterocyclic amines under microwave
      irradiation. The structures of all the novel products were elucidated based on
      elemental analysis and spectral data. In addition, the biological activity of the
      newly synthesized compounds was evaluated and the results obtained indicate their
      potency as anti-inflammatory, analgesic and anti- ulcer agents. The binding
      mechanism of the most active compounds was studied using MOE to analyze the
      molecular interactions.

PMID- 29595109
TI  - Levosimendan Reduces Prostaglandin F2a-dependent Vasoconstriction in
      Physiological Vessels and After Experimentally Induced Subarachnoid Hemorrhage.
AB  - BACKGROUND: Delayed cerebral vasospasm (dCVS) following aneurysmal subarachnoid
      hemorrhage (aSAH) is (next to possible aneurysm rebleeding, cortical spreading
      depression and early brain injury) one of the main factors contributing to poor
      overall patient outcome. Since decades, intensive research has been ongoing with
      the goal of improving our understanding of the pathophysiological principles
      underlying dCVS. Endothelin-1 (ET-1) and prostaglandin F2 alpha (PGF2a) seem to
      play a major role during dCVS. The synthesis of ET-1 is enhanced after
      subarachnoid hemorrhage (SAH) to mediate a long-lasting vasoconstriction, and
      PGF2a contributes to cerebral inflammation and vasoconstriction. Under
      physiological conditions, levosimendan (LS) demonstrates an antagonistic effect
      on PGF2a-induced cerebral vasoconstriction. Thus, the intention of the present
      study was to analyze potentially beneficial interactions in a pathophysiological
      situation. METHODS: A modified double hemorrhage model was used. Functional
      interactions between the calcium-sensitizing action of LS and the
      vasoconstrictive properties of PGF2a were investigated. RESULTS: After pre
      incubation with LS, followed by application of PGF2a, a significant decrease in
      maximum contraction (Emax) for sham-operated animals was found (Emax 28% with LS,
      Emax 56% without LS). Using the same setting after SAH, the vessel segments did
      not reach a statistically significant contraction (but similar like the sham
      operated vessels), neither for Emax nor pD2 (-log10EC50) nor EC50 (i.e., the
      concentration at which half of the maximal effect occurs). LS series in sham
      animals were performed by pre-incubation with PGF2a. The resultant Emax showed a
      statistically strong significance concerning a higher vasorelaxation compared
      with a solvent control group. Vessel segment relaxation was significantly
      stronger in the same experimental setup after SAH. CONCLUSION: Under
      physiological and pathophysiological circumstances, LS reduced and
      dosedependently reversed PGF2a-induced vasoconstriction. These results can be
      applied to further developing methods to antagonize dCVS after aSAH.

PMID- 29595110
TI  - Coumarin Compounds in Medicinal Chemistry: Some Important Examples from the Last
      Years.
AB  - Coumarins are natural products characterized as 1,2 benzopyrones widely
      distributed in plants, as well as, in many species of fungi and bacteria.
      Nowadays, many synthetic procedures allow the discovery of coumarins with
      expanded chemical space. The ability to exert noncovalent interactions with many
      enzymes and receptors in live organisms lead the coumarins to exhibit a wide
      range of biological activities and applications. Then, this manuscript provides
      an overview of the use of coumarins compounds in medicinal chemistry in treating
      many diseases. Important examples of the last years have been selected concerning
      the activities of coumarins as anticoagulant, anticancer, antioxidant, antiviral,
      anti-diabetics, anti-inflammatory, antibacterial, antifungal and anti
      neurodegerative agents. Additionally, it also includes applications of coumarins
      as fluorescent sensors for biological systems. Thus, this work aims to contribute
      to the development of new rational research projects for the treatment and
      diagnosis of pathologies using coumarin derivatives.

PMID- 29595111
TI  - Looking for New Inhibitors for the Epidermal Growth Factor Receptor.
AB  - Epidermal Growth Factor Receptor (EGFR) is still the main target of the Head and
      Neck Squamous Cell Cancer (HNSCC) because its overexpression has been detected in
      more than 90% of this type of cancer. This overexpression is usually linked with
      more aggressive disease, increased resistance to chemotherapy and radiotherapy,
      increased metastasis, inhibition of apoptosis, promotion of neoplastic
      angiogenesis, and, finally, poor prognosis and decreased survival. Due to this
      reason, the main target in the search of new drugs and inhibitors candidates is
      to downturn this overexpression. Quantitative Structure-Activity Relationship
      (QSAR) is one of the most widely used approaches while looking for new and more
      active inhibitors drugs. In this contest, a lot of authors used this technique,
      combined with others, to find new drugs or enhance the activity of well-known
      inhibitors. In this paper, on one hand, we will review the most important QSAR
      approaches developed in the last fifteen years, spacing from classical 1D
      approaches until more sophisticated 3D; the first paper is dated 2003 while the
      last one is from 2017. On the other hand, we will present a completely new QSAR
      approach aimed at the prediction of new EGFR inhibitors drugs. The model
      presented here has been developed over a dataset consisting of more than 1000
      compounds using various molecular descriptors calculated with the DRAGON 7.0(c)
      software.

PMID- 29595112
TI  - Synthesis and Biological Evaluation of Coumarins Derivatives as Potential
      Inhibitors of the Production of Pseudomonas aeruginosa Virulence Factor
      Pyocyanin.
AB  - Antimicrobial Resistance (AMR) is a serious problem for the humans since it
      threatens the effective prevention and treatment of an ever-increasing range of
      infections caused by bacteria, parasites, viruses and fungi. One way around this
      problem is to act on the virulence factors, produced by bacteria, which increase
      their infection effectiveness. In view of these facts, new coumarin derivatives
      were synthesized and evaluated for their anti-virulence biological activity
      towards Pseudomonas aeruginosa. The results suggest that coumarin derivatives
      with a secondary carbon at C-3 position reduces P. aeruginosa growth whereas
      compounds with one additional substituent have a significant effect over
      pyocyanin production (10k EC50 7 +/- 2 uM; 10l EC50 42 +/- 13 uM). Moreover, 10k
      reduces P. aeruginosa motility and biofilm formation, what is compatible with a
      quorum sensing related mechanism of action.

PMID- 29595113
TI  - Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in
      Metastatic Colorectal Cancer.
AB  - BACKGROUND: Colorectal cancer is one of the most common malignancies in the
      United States, with a large proportion of patients presenting with metastatic
      disease or developing a recurrence. Systemic chemotherapy is the mainstay of
      therapy in this setting. There is a clear benefit in the addition of bevacizumab
      or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and
      irinotecan-based regimens which can be considered for first-line therapy.
      However, many significant questions remain as to which agent reflects best
      practice. OBJECTIVE: Our review aimed to elucidate the benefit of adding
      bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer
      based on primary tumor location and a variety of other disease- and patient
      related factors, addressing the paucity of evidence that currently exists in this
      area and contributing to current literature and clinical practices. METHODS: The
      primary endpoints of the study were first Progression-Free Survival (PFS) and
      Overall Survival (OS). Secondary endpoints included best response to first- and
      second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS,
      cost of therapy, and an assessment of other patient- and disease-related factors
      affecting PFS and OS. RESULTS: While there were trends towards improved OS in
      patients with left-sided primary tumors (n=57) compared to those with right-sided
      disease (n=23), there were no significant differences between the two groups in
      either primary endpoint. While no differences were found for patients with left-
      or right- sided tumors stratified by add-on agent, these analyses were limited by
      the small number of patients receiving cetuximab with first-line therapy (n=4).
      However, the bevacizumab cohort (n=76) was sizable enough to provide ample data
      and produce clinically relevant results. Add-on therapy with bevacizumab in our
      study achieved impressive survival outcomes in both left-sided (median first PFS
      = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21-53 months) and
      right-sided (median first PFS = 13 months, 95% CI 9-17 months; median OS = 37
      months, 95% CI 22-52 months) disease. CONCLUSION: These results raised questions
      regarding the true significance of primary tumor location when selecting
      bevacizumab or cetuximab for first-line therapy, particularly the current thought
      of using cetuximab for left-sided tumors. While the superiority of bevacizumab
      over cetuximab in rightsided disease remained evident upon comparison of our
      analysis with historical controls, survival outcomes with the agent in our
      analysis appeared to be similar to that of cetuximab in CRYSTAL, FIRE- 3, and
      CALGB/SWOG 80405 in left-sided disease. Further study is required to determine if
      bevacizumab truly does produce similar outcomes to cetuximab in left-sided
      primary tumors.

PMID- 29595114
TI  - Some Thiazole Derivatives Combined With Different Heterocycles : Cytotoxicity
      Evaluation And Apoptosis Inducing Studies.
AB  - BACKGROUND: Thiazole ring is an outstanding structure found in many biologically
      active compounds and clinically available drugs. Because of synthesis simplicity
      of its derivatives and having a wide range of biological aspects along with high
      effectiveness, new thiazole derivatives have been studied by medicinal chemists
      since many years. OBJECTIVE: Therefrom some thiazole compounds combined with
      different heterocyclic rings were acquired in this study. Novel 5-(4-substituted
      benzylidene)-2-[(4,5-dimethylthiazol-2-yl)amino]thiazol-4(5H)-one derivatives (4a
      g) and 2-(heteroaryl-2/3/5-yl)thio-N-(4,5-dimethylthiazol-2-yl)acetamide (4h-p)
      derivatives were synthesized starting from 2-amino-4,5-dimethylthiazole. The
      obtained compounds were evaluated to determine their antiproliferative activity.
      METHOD: Final compounds (4a-g) were obtained with ring closure reaction; other
      final compounds (4h-p) were acquired via the reaction of mercapto heterocycles
      with Hantzsch thiazole synthesis intermediate. To evaluate antiproliferative
      activity of them, compounds were tested on A549 adenocarcinomic human alveolar
      basal epithelial cells line, C6 rat glioma cell line and NIH/3T3 mouse embryo
      fibroblast cell line according to conventional MTT method. Besides, selected
      compounds were studied to find out which pathway cell deaths caused from via
      Annexin V/PI staining. RESULTS: Compounds 4f, 4j and 4p exhibited the highest
      cytotoxicity on A549 with a non-toxic profile. Also, 4f, 4h, 4j and 4p were
      determined as the most antiproliferative compounds on C6 cell line. Furthermore,
      compound 4p induced apoptosis of A549 cell with a level of 23.5% and compound 4h
      induced C6 cell with a level of 37.5%. CONCLUSION: Considering the structure of
      the compounds, although thiazolidine containing compounds 4a-g exhibited higher
      activity in general, compounds 4p containing 5-chlorobenzothiazole moiety showed
      the highest cytotoxicity. It could be expressed with conspicuous antitumor
      efficiency of benzothiazole ring.

PMID- 29595115
TI  - Efficacy and Non Invasive Treatment of Sialorrhea in the Goldenhar Syndrome.
AB  - BACKGROUND AND OBJECTIVE: Goldenhar syndrome (ocular-auricular-vertebral
      syndrome), a rare congenital condition arising from defects in the first and
      second brachial arches, consists in clinical variety of features ranging from
      facial abnormalities, ear-eye abnormalities, vertebral defects and congenital
      heart problems and severe obstructive sleep apnea. Due to craniofacial
      abnormalities, patients presents mechanical obstructive phenomena and sialorrhea
      that cause prone position, language's fastening, use of nasopharyngeal cannulas
      and tracheal intubation. METHODS: In this article, we report a case of a 16 years
      old child affected by Goldenhar syndrome and sialorrhea to demonstrate
      improvement of the daily patient management, through inoculations of botulinum
      toxin type A. Due to severe sialorrhea which caused tracheobronchial daily
      aspirations, the caregivers used an external aspirators. RESULTS: In the first
      infiltration (August 2016) the parotid and submandibular glands bilaterally were
      inoculated with incobotulinum toxin type A (Xeomin(r), Merz Pharma) with dosages
      of 5 UI for each of them, for a total of 20 UI without clinical efficacy (no
      quantitative and qualitative saliva reducing during 3 months). In the second
      (November 2016) and third (February 2017) infiltrations each parotid and each
      submandibular glands were injected with a (dosage of 7 UI and 5 UI respectively
      (total of 24 UI of incobotulinumtoxin A) with important clinical results (saliva
      production and tracheo-bronchial aspirations reduced). CONCLUSION: Therefore,
      botulinum toxin type A could be a good and non invasive treatment of sialorrhea
      in Goldenhar syndrome to improve oral hygiene and daily patient management.

PMID- 29595116
TI  - Ameliorative Potentials of Methanol Fractions of Cnidoscolus aconitifolius on
      Some Hematological and Biochemical Parameters in Streptozotocin Diabetic Rats.
AB  - BACKGROUND: There is a paucity of information in the literature on the effect of
      Cnidoscolus aconitifolius on the hematological, coagulation activities,
      electrolyte balance and antioxidant activities of humans or animals. OBJECTIVES:
      To determine the ameliorative potentials of methanol fractions of Cnidoscolus
      aconitifolius on hematological, coagulation, electrolyte, hepatic and renal
      antioxidant activities of streptozotocininduced diabetic rats using standard
      techniques. METHOD: Thirty rats, distributed into five groups of six rats each
      were used for this study. Groups 1 and 2 (normal and diabetic controls) received
      1 ml/kg normal saline. Groups 3 and 4 received methanol fractions of Cnidoscolus
      aconitifolius (at 250 and 500 mg/kg). Group 5 was administered glibenclamide (2.5
      mg/kg). RESULTS: The diabetic control had decreased (P<0.05) white blood cells,
      red blood cells, hemoglobin, packed cell volume, mean cell hemoglobin, mean cell
      hemoglobin concentration, lymphocytes, eosinophils, thrombin time, prothrombin
      time, activated partial thromboplastin time, sodium, potassium, bicarbonate ions,
      hepatic and renal superoxide dismutase, catalase and glutathione peroxidase
      activities; increased (P<0.05) neutrophils, fibrinogen and platelets counts,
      chloride ion levels compared with the normal control while their monocytes were
      not different (P>0.05) from that of the normal control. Basophils were not
      detected in all the groups that were studied. The methanol fraction at 500 mg/kg
      was more potent than the methanol fraction at 250 mg/kg or glibenclamide (at 2.5
      mg/kg) in ameliorating the hematological parameters, serum electrolytes and
      oxidative stress in the hepatic and kidney tissues of the diabetic rats
      suggesting its potentials in the management of diabetic complications.
      CONCLUSION: Finally, the biological properties demonstrated by the methanol
      fraction could be attributed to the presence of octadecanoic acid, n-hexadecanoic
      acid, eicosanoic acid, tetradecanoic acid and n-hexadecanoic acid in it as
      previously reported.

PMID- 29595117
TI  - Non-Alcoholic Fatty Pancreas Disease (NAFPD): A Silent Spectator or the Fifth
      Component of Metabolic Syndrome? A Literature Review.
AB  - BACKGROUND AND OBJECTIVE: Fat accumulation in the pancreas has remained a
      relatively unknown disease since it was initially described in 1926. However, it
      has gained increasing attention in the past two decades with the emergence of the
      obesity epidemic. Pancreatic steatosis is a general term used for fat
      accumulation in the pancreas. It is further classified into fatty replacement,
      fatty infiltration, lipomatous pseudo-hypertrophy, non-alcoholic fatty pancreas
      disease (NAFPD) and non-alcoholic fatty steatopancreatitis (NASP). NAFPD is
      defined as obesity-associated accumulation of fat in the pancreas without
      significant alcohol consumption. Data on the prevalence of NAFPD are limited due
      to a lack of standardized screening tests. METHODS: MEDLINE/PubMed was searched
      to find relevant studies and abstracts on pancreatic steatosis. RESULTS:
      Pancreatic fat can be quantified by various imaging techniques including
      ultrasonography, computed tomography, magnetic resonance imaging and magnetic
      resonance spectroscopy. The pathophysiology of NAFPD has not been completely
      understood. Chronic exposure of beta-cells to hyperglycemia and higher levels of
      free fatty acids results in increased intracellular triglyceride accumulation,
      which ultimately causes reduced insulin secretion, insulin resistance, cell
      apoptosis and subsequent fatty replacement. This vicious cycle likely is a
      determining factor in the development of diabetes mellitus and metabolic
      syndrome. There is no approved pharmacologic therapy for NAFPD. Caloric
      restriction might have a role in normalization of beta-cell function by reducing
      pancreatic fat content. Troglitazone (blend of telmisartan and sitagliptin) has
      demonstrated effectiveness in animal models but is still in experimental stages.
      CONCLUSION: The cause and effect relationship between the metabolic syndrome and
      NAFPD has not yet been established. Further studies are required to study the
      effect of NAFPD on glucose hemostasis.

PMID- 29595118
TI  - Evaluation of the Antidiabetic Property of Capparis Ovata Desf. Var. Palaestina
      Zoh. Extracts Using In vivo and In vitro Approaches.
AB  - BACKGROUND AND OBJECTIVE: This paper is focused on evaluating the various
      biological activities of C. ovata var. palaestina extracts which could
      beneficially influence diabetes and its complications. METHODS: Alloxan-induced
      diabetic BALB-c mice were administered intraperitoneally with 100, 300, 500mg/kg
      doses of ethanol and aqueous extracts of buds and fruits. Furthermore, HPLC,
      phenolic and flavonoid compounds analysis, ABTS and DPPH free radical scavenging
      activity, anti-inflammatory activity, agar well diffusion and MIC tests were
      carried out. RESULTS: Fruit-aqueous; 100mg/kg, 300mg/kg and bud-aqueous; 500mg/kg
      extracts showed significant hypoglycemic activity. All extracts indicated
      important antioxidant activity, however, bud-aqueous extract demonstrated the
      most potent activity. HPLC study exhibited that rutin is found in high amounts in
      bud-aqueous and bud-ethanol extracts. Furthermore, the bud-aqueous extract
      depicted stronger and broader antimicrobial activity than other extracts. Fruit
      ethanol and bud-ethanol extracts denoted the most potent anti-inflammatory effect
      even though this effect was significantly shown by all extracts. Finally, high
      levels of phenolic and flavonoid content were involved in all extracts, but the
      highest levels were found in fruit-ethanol and bud-ethanol extracts. CONCLUSION:
      The results showed that extracts which indicated hypoglycemic, antioxidant,
      antiinflammatory, antimicrobial activities may provide a valuable contribution to
      the management of diabetes and its complications.

PMID- 29595119
TI  - Cytochrome P450 3A4 Induction: Lumacaftor versus Ivacaftor Potentially Resulting
      in Significantly Reduced Plasma Concentration of Ivacaftor.
AB  - BACKGROUND & OBJECTIVE: Since the release of ivacaftor-lumacaftor, several red
      flags have been raised that highlight the clinical efficacy of this combination
      strategy that may be limited due to antagonistic drug-drug interactions. METHOD:
      The effect of ivacaftor, its major metabolites M1 and M6, lumacaftor and the
      novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator
      tezacaftor at 10 ug/mL on the enzymatic activity of the major xenobiotic
      metabolizing enzymes CYP1A2 and CYP3A4 as well as the minor enzymes CYP2B6 and
      CYP2C9 was assayed. RESULTS: Lumacaftor (3.74 x 105 +/- 3.11 x 104 RLU), and
      ivacaftor-M6 (3.43 x 105 +/- 7.61 x 103 RLU) markedly induced the activity of
      CYP3A4. Ivacaftor (2.22 x 105 +/- 3.94 x 104 RLU) showed a lower relative ratio
      of luminescence units compared to chloramphenicol (3.17 x 105 +/- 1.55 x 104
      RLU). Interestingly, ivacaftor-M1 (6.74 x 104 +/- 3.09 x 104 RLU) and the novel
      CFTR modulator tezacaftor (2.40 x 104 +/- 8.14 x 104 RLU) did not show CYP3A4
      induction. In the CYP1A2 and CYP2C9 assay, all metabolites showed a decrease in
      the ratio of luminescence units compared to the controls. Ivacaftor, its major
      metabolites, lumacaftor and tezacaftor all showed a slight increase in the ratio
      of luminescence units compared to the control rifampin with CYP2B6. CONCLUSION:
      All in all, present findings would suggest that lumacaftor and ivacaftor-M6 are
      strong inducers of CYP3A4, potentially reducing ivacaftor concentrations;
      ivacaftor itself induces CYP3A4 to some extent.

PMID- 29595120
TI  - State-of-the-Art on Viral microRNAs in HPV Infection and Cancer Development.
AB  - BACKGROUND: High-risk HPV subtypes are driving forces for human cancer
      development: HPV-16 and HPV-18 are responsible for most HPV-caused cancers.
      OBJECTIVE: This review describes the present knowledge on HR-HPV genomes coding
      potential for viral miRNAs. METHODS: HPV subtypes miRNA database, VIRmiRtar, has
      been constructed applying bioinformatics and a computational method, ViralMir,
      exploiting structural features, the presence of hairpins, and validation by
      comparison with RNA sequencing datasets. RESULTS: Several miRNA candidates have
      been localised in the genomes of high-risk HPV subtypes. Among these, HPV-16 miR
      1, miR-2 and miR-3. The database contains a list of host candidate gene targets
      that may be responsible for the oncogenesis in the various cellular environments.
      CONCLUSION: miRNA silencing therapies, based on specific cellular uptake of miRNA
      mimics and antagomiRs, directed towards HPV encoded miRNAs and/or microRNAs
      deregulated in the host cells, could be a valuable approach to support
      pharmaceutical interventions in the treatment of HPV dependent cancers.

PMID- 29595121
TI  - The Expansion Segments of Human 28S rRNA Match MicroRNAs Much Above 18S rRNA or
      Core Segments.
AB  - BACKGROUND: The size of eukaryotic 25-28S rRNAs shows a progressive
      phylogenetically linked increase which is pronounced in mammals, and especially
      in hominids. The increase is confined to specific expansion segments, inserted at
      points that are highly conserved from yeast to man. These segments also show a
      progressive increase in nucleotide bias, mostly the GC bias. Substantial parts of
      the large expansion segments 7, 15 and 27 of 28S rRNA are known to be exposed at
      the ribosome surface, with no clear association with ribosomal proteins. These
      segments could bind extraneous RNAs and proteins to support regulatory events.
      METHODS: This study examined the possible canonical matching of human 28S rRNA
      and 18S rRNA segments with 2586 human microRNAs. This was compared with matching
      of the microRNAs to sectors of 18810 human mRNAs. RESULTS: The overall matching
      was rather similar across 18S rRNA segments and core segments of 28S rRNA.
      However, the expansion segments of 28S rRNA (abbreviated ESL) collectively have a
      much higher (up to two-fold) capacity for the canonical association with
      microRNAs. This is pronounced in large ESL, and is found to strongly relate to
      the GC content of microRNAs. CONCLUSION: Oligonucleotides and microRNAs of high
      GC content through a strong canonical hydrogen bonding could have large activity
      in regulation of subcellular RNAs. In view of the considerable abundance of
      ribosomal RNAs in many mammalian tissues, ESL could constitute an important
      component of microRNA balance, possibly serving to lower the availability of GC
      rich microRNAs (and thereby help conservation of GC-rich mRNAs).

PMID- 29595122
TI  - Population pharmacokinetics and pharmacodynamics of fondaparinux in Japanese
      patients after artificial total knee replacement?.
AB  - OBJECTIVE: This study was designed to clarify the factors affecting the efficacy,
      adverse events, and pharmacokinetics of fondaparinux in Japanese patients
      undergoing artificial knee replacement surgery. MATERIALS AND METHODS:
      Fondaparinux (1.5 mg/d) was administered subcutaneously to patients (n = 30) at
      24 hours after surgery, and blood samples were taken at various time points
      thereafter. Venous thromboembolism (VTE), presence of bleeding, and
      pharmacokinetics were evaluated. Multivariate analysis and population
      pharmacokinetic analysis were performed to detect factors that necessitated
      withdrawal of fondaparinux and individual differences in its pharmacokinetics.
      RESULTS: VTE was observed in 9 patients (3 for whom administration was continued
      and 6 for whom withdrawal was necessary). The maximum plasma concentration of
      fondaparinux was found to be a significant factor determining withdrawal of the
      drug. Population pharmacokinetic analysis demonstrated that individual renal
      function and body weight were significant factors associated with apparent
      clearance and volume of distribution, respectively. CONCLUSIONS: A high maximum
      plasma concentration of fondaparinux may result in subcutaneous hemorrhage,
      necessitating withdrawal of fondaparinux administration. The patient's kidney
      function and body weight also contribute to individual differences in
      pharmacokinetics. We recommend considering an adjustment to the dose of
      fondaparinux based on body weight in patients undergoing artificial knee
      replacement surgery.?.

PMID- 29595123
TI  - Investigation of a potential drug-drug interaction between salbutamol and
      ambroxol and bioequivalence of a new fixed-dose combination containing these two
      drugs in healthy Chinese subjects.
AB  - OBJECTIVES: The aims of the study were to investigate the potential drug-drug
      interaction between salbutamol and ambroxol, the bioequivalence of the new fixed
      dose combination containing salbutamol and ambroxol compared with co
      administration of the two separate formulations, and to describe the safety and
      tolerability of the fixed-dose combination formulation in healthy Chinese
      volunteers. MATERIALS AND METHODS: An open-label, single-dose, four-treatment,
      four-period crossover study for evaluation of drug-drug interaction and
      bioequivalence (n = 24) was performed. Each participant received salbutamol 4 mg,
      ambroxol 15 mg, salbutamol 4 mg co-administered with ambroxol 15 mg or fixed-dose
      combination formulation (salbutamol 4 mg and ambroxol 15 mg). Plasma
      concentrations of two analytes were determined with the use of validated LC-MS/MS
      method. Safety and tolerability were assessed by recording adverse events.
      RESULTS: Co-administration of salbutamol and ambroxol was not associated with a
      significant influence on single salbutamol or ambroxol pharmacokinetics. After
      statistical comparisons of log-transformed C<sub>max</sub> and AUC of salbutamol
      and ambroxol between fixed-dose combination and concomitant treatments, all 90%
      confidence intervals of geometric mean ratios were within the predefined
      equivalence range of 80 - 125%. No serious adverse events were reported, and all
      treatments were safe and well tolerated in Chinese healthy subjects. CONCLUSION:
      There were no significant drug-drug pharmacokinetic interactions between
      salbutamol and ambroxol after oral administration. The new formulation was
      bioequivalent to the co-administration of two drugs in separate dosage forms.?.

PMID- 29595124
TI  - Absence of 1p/19q codeletion in oligodendroglioma-like areas of pilocytic
      astrocytomas.
AB  - The presence of oligodendroglioma-like areas in pilocytic astrocytoma may give
      rise to pathologic diagnostic uncertainty. This study aims to determine if the
      oligodendroglioma-like areas present in some pilocytic astrocytomas (PA) possess
      the signature 1p/19q codeletion that is characteristic of classical
      oligodendroglioma. Array comparative genomic hybridization was carried out on 12
      PA samples, from which oligodendroglioma-like areas were microdissected and used
      as the template DNA source. 1p/19q codeletions were not found in any of the
      oligodendroglioma areas in PAs. We conclude that PAs with oligodendroglioma-like
      areas do not share the same molecular genetics as classic oligodendroglioma.?.

PMID- 29595125
TI  - A 3-year old female with an atypical pineal tumor.

PMID- 29595127
TI  - Redefining the 'E' in EBM.

PMID- 29595126
TI  - The legacy of retinoblastoma: Three unusual tumors in a woman with a history of
      heritable retinoblastoma - a case report.

PMID- 29595128
TI  - Has too much cardiology been sent into the appropriateness ORBITA?

PMID- 29595129
TI  - Assessing the validity of surrogate endpoints in the context of a controversy
      about the measurement of effectiveness of hepatitis C virus treatment.
AB  - Surrogate endpoints are often used in clinical trials, as they allow for indirect
      measures of outcomes (eg, shorter trials with less participants). Improvements in
      surrogate endpoints (eg, reduction in low density lipoprotein cholesterol,
      normalisation of glycated haemoglobin) achieved with an intervention are,
      however, not always associated with improvements in patient-important outcomes.
      The common tendency in evidence-based medicine is to view results based on
      surrogate endpoints as less certain than results based on long term, final
      patient-important outcomes and rate them as 'lower quality evidence'. However,
      careful appraisal of the validity of a surrogate endpoint as a measure of the
      final, patient-important outcome is more useful than an automatic judgement. In
      this guide, we use a contemporary and currently highly debated example of the
      surrogate endpoint 'sustained viral response' (ie, viral eradication considered
      to represent successful treatment) in patients treated for chronic hepatitis C
      virus. We demonstrate how the validity of a surrogate endpoint can be critically
      appraised to assess the quality of the evidence (ie, the certainty in estimates)
      and the implications for decision-making.

PMID- 29595130
TI  - Verification bias.
AB  - This article is part of the Catalogue of Bias series. We present a description of
      verification bias, and outline its potential impact on research studies and the
      preventive steps to minimise its risk. We also present teaching slides in the
      online supplementary file. Verification bias (sometimes referred to as 'work-up
      bias') concerns the test(s) used to confirm a diagnosis within a diagnostic
      accuracy study. Verification bias occurs when only a proportion of the study
      participants receive confirmation of the diagnosis by the reference standard
      test, or if some participants receive a different reference standard test.

PMID- 29595131
TI  - Network meta-analysis: the highest level of medical evidence?

PMID- 29595133
TI  - PCI does not improve outcomes for patients with stable angina.

PMID- 29595132
TI  - Synergistic effects of blood pressure-lowering drugs and statins: systematic
      review and meta-analysis.
AB  - BACKGROUND: Synergistic effects of blood pressure-lowering drugs and statins are
      unknown, but are key to risk-based treatment decision strategies and fixed
      combination polypills. OBJECTIVE: We conducted a systematic literature review and
      meta-analysis to test the hypothesis that the combined relative effects of blood
      pressure-lowering drugs and statins on cardiovascular outcomes are
      multiplicative. STUDY SELECTION: Two persons independently searched five data
      sources and hand-searched reference lists from earliest available to December
      2017. We included factorial trials with at least two randomised interventions
      including one statin versus placebo factor and one blood pressure-lowering
      drug/more intense blood pressure-lowering regimen versus placebo/less intense
      regimen factor, and reported cardiovascular events or mortality as outcomes. We
      tested interactions as departures from additivity or multiplicativity using mixed
      effects logistic regression models. FINDINGS: Seven out of 1017 screened studies
      fulfilled the selection criteria, contributing a total of 27 020 patients with
      857 major cardiovascular events and 725 deaths. The relative risk reduction of
      major cardiovascular events with active/more intense blood pressure-lowering
      regimen was not materially different in subgroups randomised to statins (risk
      ratio 0.81, 95% CI 0.66 to 1.00) or placebo (0.94, 0.79 to 1.11). Likewise,
      statin effects were not substantially different in subgroups randomised to
      active/more intense blood pressure-lowering regimen (0.69, 0.57 to 0.85) or
      placebo/less intense regimen (0.80, 0.67 to 0.96). No departures from either
      additivity or multiplicativity were observed. Heterogeneity was low. CONCLUSIONS:
      The combined relative effects of blood pressure-lowering drugs and statins on
      cardiovascular events were multiplicative. This supports risk-based treatment
      decision strategies and fixed-combination polypills.

PMID- 29595134
TI  - Intensive blood pressure-lowering reduces mortality and cardiovascular events in
      older people.

PMID- 29595135
TI  - Risk score identifies patients who will benefit from prolonged dual antiplatelet
      therapy.

PMID- 29595136
TI  - Natriuretic peptide guided therapy for management of patients with heart failure
      does not show improvement compared with usual medical therapy alone.

PMID- 29595137
TI  - Antibiotic prescribing does not decrease complications in adult patients with
      lower respiratory tract infections.

PMID- 29595138
TI  - Hypoxia and signs of increased work of breathing are most strongly associated
      with radiographic pneumonia in children.

PMID- 29595139
TI  - Correction: What does expert opinion in guidelines mean? a meta-epidemiological
      study.

PMID- 29595140
TI  - Greater cognitive decline relative to normal ageing occurs at least 10 years
      prior to clinical dementia diagnosis.

PMID- 29595141
TI  - Regarding minimal clinically relevant differences for superiority margins.

PMID- 29595142
TI  - Fluorescence from a single Symbiodinium cell.
AB  - The partnership between coral and its algal symbionts, Symbiodinium, is crucial
      to the global environment. Yet, the regulatory process within the photosynthetic
      machinery of Symbiodinium is still not clearly understood. Here, we studied the
      influence of light stress from focussed red and blue lasers on single
      Symbiodinium cells. Fluorescence signals were measured to show cell response.
      Increasing the incident laser power or the exposure time resulted in an increase
      followed by a decline in fluorescence intensity. The trend of fluorescence
      intensity changes was associated with mechanisms of light use efficiency, non
      photochemical quenching, photoinhibition, and repair of the cell. Our study
      provides new approaches to studying the photobiology and physiology of
      Symbiodinium cells.

PMID- 29595144
TI  - Photoemission perspective on pseudogap, superconducting fluctuations, and charge
      order in cuprates: a review of recent progress.
AB  - In the course of seeking the microscopic mechanism of superconductivity in
      cuprate high temperature superconductors, the pseudogap phase- the very abnormal
      'normal' state on the hole-doped side- has proven to be as big of a quandary as
      superconductivity itself. Angle-resolved photoemission spectroscopy (ARPES) is a
      powerful tool for assessing the momentum-dependent phenomenology of the
      pseudogap, and recent technological developments have permitted a more detailed
      understanding. This report reviews recent progress in understanding the
      relationship between superconductivity and the pseudogap, the Fermi arc
      phenomena, and the relationship between charge order and pseudogap from the
      perspective of ARPES measurements.

PMID- 29595143
TI  - Matrix stiffness and tumor-associated macrophages modulate epithelial to
      mesenchymal transition of human adenocarcinoma cells.
AB  - The tumor microenvironment (TME) is gaining increasing attention in oncology, as
      it is recognized to be functionally important during tumor development and
      progression. Tumors are heterogeneous tissues that, in addition to tumor cells,
      contain tumor-associated cell types such as immune cells, fibroblasts, and
      endothelial cells. These other cells, together with the specific extracellular
      matrix (ECM), create a permissive environment for tumor growth. While the
      influence of tumor-infiltrating cells and mechanical properties of the ECM in
      tumor invasion and progression have been studied separately, their interaction
      within the complex TME and the epithelial -to-mesenchymal transition (EMT) is
      still unclear. In this work, we develop a 3D co-culture model of lung
      adenocarcinoma cells and macrophages in an interpenetrating network hydrogel, to
      investigate the influence of the macrophage phenotype and ECM stiffness in the
      induction of EMT. Rising ECM stiffness increases both tumor cell proliferation
      and invasiveness. The presence of tumor-associated macrophages and the ECM
      stiffness jointly contribute to an invasive phenotype, and modulate the
      expression of key EMT-related markers. Overall, these findings support the
      utility of in vitro 3D cancer models that allow one to study interactions among
      key components of the TME.

PMID- 29595145
TI  - Feasibility of online IMPT adaptation using fast, automatic and robust dose
      restoration.
AB  - Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and
      healthy tissue sparing, but it can be substantially compromised in the presence
      of anatomical changes. A major dosimetric effect is caused by density changes,
      which alter the planned proton range in the patient. Three different methods,
      which automatically restore an IMPT plan dose on a daily CT image were
      implemented and compared: (1) simple dose restoration (DR) using optimization
      objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3)
      isodose volume dose restoration (iDR). Dose restorations were calculated for
      three different clinical cases, selected to test different capabilities of the
      restoration methods: large range adaptation, complex dose distributions and
      robust re-optimization. All dose restorations were obtained in less than 5 min,
      without manual adjustments of the optimization settings. The evaluation of
      initial plans on repeated CTs showed large dose distortions, which were
      substantially reduced after restoration. In general, all dose restoration methods
      improved DVH-based scores in propagated target volumes and OARs. Analysis of
      local dose differences showed that, although all dose restorations performed
      similarly in high dose regions, iDR restored the initial dose with higher
      precision and accuracy in the whole patient anatomy. Median dose errors decreased
      from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR).
      High quality dose restoration is essential to minimize or eventually by-pass the
      physician approval of the restored plan, as long as dose stability can be
      assumed. Motion (as well as setup and range uncertainties) can be taken into
      account by including robust optimization in the dose restoration. Restoring
      clinically-approved dose distribution on repeated CTs does not require new ROI
      segmentation and is compatible with an online adaptive workflow.

PMID- 29595146
TI  - Assessment of linear and nonlinear/complex heartbeat dynamics in subclinical
      depression (dysphoria).
AB  - OBJECTIVE: Depression is one of the leading causes of disability worldwide. Most
      previous studies have focused on major depression, and studies on subclinical
      depression, such as those on so-called dysphoria, have been overlooked. Indeed,
      dysphoria is associated with a high prevalence of somatic disorders, and a
      reduction of quality of life and life expectancy. In current clinical practice,
      dysphoria is assessed using psychometric questionnaires and structured interviews
      only, without taking into account objective pathophysiological indices. To
      address this problem, in this study we investigated heartbeat linear and
      nonlinear dynamics to derive objective autonomic nervous system biomarkers of
      dysphoria. APPROACH: Sixty undergraduate students participated in the study:
      according to clinical evaluation, 24 of them were dysphoric. Extensive group-wise
      statistics was performed to characterize the pathological and control groups.
      Moreover, a recursive feature elimination algorithm based on a K-NN classifier
      was carried out for the automatic recognition of dysphoria at a single-subject
      level. MAIN RESULTS: The results showed that the most significant group-wise
      differences referred to increased heartbeat complexity (particularly for fractal
      dimension, sample entropy and recurrence plot analysis) with regards to the
      healthy controls, confirming dysfunctional nonlinear sympatho-vagal dynamics in
      mood disorders. Furthermore, a balanced accuracy of 79.17% was achieved in
      automatically distinguishing dysphoric patients from controls, with the most
      informative power attributed to nonlinear, spectral and polyspectral quantifiers
      of cardiovascular variability. SIGNIFICANCE: This study experimentally supports
      the assessment of dysphoria as a defined clinical condition with specific
      characteristics which are different both from healthy, fully euthymic controls
      and from full-blown major depression.

PMID- 29595147
TI  - Measuring the effective area and charge density of platinum electrodes for bionic
      devices.
AB  - OBJECTIVE: Neural stimulation is usually performed with fairly large platinum
      electrodes. Smaller electrodes increase the applied charge density, potentially
      damaging the electrode. Greater understanding of the charge injection mechanism
      is required for safe neural stimulation. APPROACH: The charge injection mechanism
      and charge injection capacity were measured by cyclic voltammetry. Electrodes
      were cleaned mechanically or by potential cycling in acidic solutions. The
      effective electrode area was measured by hydrogen adsorption or reduction of
      [Formula: see text]. MAIN RESULTS: The water window and safe potential window
      were affected by changes to electrolyte, electrode size, polishing method and
      oxygen concentration. Capacitance and Faradaic current contribute to the charge
      injection capacity. Varying voltammetric scan rate (measurement time), electrode
      size, polishing method, potential window, electrolyte and oxygen concentration
      affected the charge injection capacity and ratio of oxidation to reduction
      charge. Hydrogen adsorption in acidic solutions provided an inaccurate effective
      electrode area. Reduction of a solution phase redox species with a linear or
      radial diffusion profile could provide an effective electrode area. The charge
      density (charge injection capacity divided by electrode area) of a platinum
      electrode is dependent on the charge injection capacity and electrode area
      measurement technique. By varying cyclic voltammetric conditions, the charge
      density of platinum ranged from 0.15 to 5.57 mC cm-2. SIGNIFICANCE: The safe
      potential window, charge injection mechanism, charge injection capacity and
      charge density of platinum depends on electrolyte, size of the electrode, oxygen
      concentration and differences in electrode polishing method. The oxidation and
      reduction charge injection capacities are not equal. Careful control of a
      platinum electrodes surface may allow larger charge densities and safe use of
      smaller electrodes. New electrode materials and geometries should be tested in a
      consistent manner to allow comparison of potential suitability for neural
      stimulation.

PMID- 29595148
TI  - Colloidal lithography nanostructured Pd/PdO x core-shell sensor for ppb level H2S
      detection.
AB  - In this work we report on plasma oxidation of palladium (Pd) to form reliable
      palladium/palladium oxide (Pd/PdO x ) core-shell sensor for ppb level H2S
      detection and its performance improvement through nanostructuring using hole-mask
      colloidal lithography (HCL). The plasma oxidation parameters and the sensor
      operating conditions are optimized to arrive at a sensor device with high
      sensitivity and repeatable response for H2S. The plasma oxidized
      palladium/palladium oxide sensor shows a response of 43.1% at 3 ppm H2S at the
      optimum operating temperature of 200  degrees C with response and recovery times
      of 24 s and 155 s, respectively. The limit of detection (LoD) of the plasma
      oxidised beam is 10 ppb. We further integrate HCL, a bottom-up and cost-effective
      process, to create nanodiscs of fixed diameter of 100 nm and varying heights (10,
      15 and 20 nm) on 10 nm thin Pd beam which is subsequently plasma oxidized to
      improve the H2S sensing characteristics. The nanostructured Pd/PdO x sensor with
      nanodiscs of 100 nm diameter and 10 nm height shows an enhancement in sensing
      performance by 11.8% at same operating temperature and gas concentration. This
      nanostructured sensor also shows faster response and recovery times (15 s and 100
      s, respectively) compared to the unstructured Pd/PdO x counterpart together with
      an experimental LoD of 10 ppb and the estimated limit going all the way down to 2
      ppb. Material characterization of the fabricated Pd/PdO x sensors is done using
      UV-vis spectroscopy and x-ray photoemission spectroscopy.

PMID- 29595149
TI  - Tunable single and double emission semiconductor nanocrystal quantum dots: a
      multianalyte sensor.
AB  - We have prepared stable colloidal CdTe and CdTe/ZnS core-shell quantum dots (QDs)
      using hot injection chemical route. The developed CdTe QDs emit tunable single
      and dual photoluminescence (PL) bands, originating from the direct band edge and
      the surface state of QDs, as evident by the steady-state and time-resolved
      spectroscopy. The developed CdTe and CdTe/ZnS QDs act as optical sensors for the
      detection of metal ions (e.g., Fe2+ and Pb2+) in the feed water. The PL quenching
      in the presence of analytes has been examined by both the steady-state and time
      resolved PL spectroscopy. The linear Stern-Volmer (S-V) plots obtained for PL
      intensity and lifetime as a function of metal ion concentration demonstrates the
      diffusion-mediated collisional quenching as a dominant mechanism together with
      the possibility of fluorescence resonance energy transfer. Thus, the prepared
      core and core-shell QDs which cover a broad spectral range of white light with
      high quantum yield (QY) are highly sensitive to the detection of metal ions in
      feed water and are also important for biological applications (Ratnesh and Mehata
      2017 Spectrochim. Acta A: Mol. Biomol. Spectro. 179 201-10).

PMID- 29595150
TI  - Spiraling contaminant electrons increase doses to surfaces outside the photon
      beam of an MRI-linac with a perpendicular magnetic field.
AB  - The transverse magnetic field of an MRI-linac sweeps contaminant electrons away
      from the radiation beam. Films oriented perpendicular to the magnetic field and 5
      cm from the radiation beam edge show a projection of the divergent beam,
      indicating that contaminant electrons spiral along magnetic field lines and
      deposit dose on surfaces outside the primary beam perpendicular to the magnetic
      field. These spiraling contaminant electrons (SCE) could increase skin doses to
      protruding regions of the patient along the cranio-caudal axis. This study
      investigated doses from SCE for an MRI-linac comprising a 7 MV linac and a 1.5 T
      MRI scanner. Surface doses to films perpendicular to the magnetic field and 5 cm
      from the radiation beam edge showed increased dose within the projection of the
      primary beam, whereas films parallel to the magnetic field and 5 cm from the beam
      edge showed no region of increased dose. However, the dose from contaminant
      electrons is absorbed within a few millimeters. For large fields, the SCE dose is
      within the same order of magnitude as doses from scattered and leakage photons.
      Doses for both SCE and scattered photons decrease rapidly with decreasing beam
      size and increasing distance from the beam edge.

PMID- 29595151
TI  - Nitrogen removal via a single-stage PN-Anammox process in a novel combined
      biofilm reactor.
AB  - This study developed a partial nitrification (PN) and anaerobic ammonia oxidation
      (Anammox) process for treating high-ammonia wastewater using an innovative
      biofilm system in which ammonia oxidizing bacteria grew on fluidized Kaldnes (K1)
      carriers and Anammox bacteria grew on fixed acryl resin carriers. The airlift
      loop biofilm reactor (ALBR) was stably operated for more than 4 months under the
      following conditions: 35 +/- 2  degrees C, pH 7.5-8.0 and dissolved oxygen (DO)
      of 0.5-3.5 mg/L. The results showed that the total nitrogen removal efficiency
      reached a maximum of 75% and the total nitrogen removal loading rate was above
      0.4 kg/(d.m3). DO was the most efficient control parameter in the mixed biofilm
      system, and values below 1.5 mg/L were observed in the riser zone for the PN
      reaction, while values below 0.8 mg/L were observed in the downer zone for the
      Anammox reaction. Scanning electron microscopy and Fluorescence In Situ
      Hybridization images showed that most of the nitrifying bacteria were distributed
      on the K1 carriers and most of the Anammox bacteria were distributed within the
      acryl resin carriers. Therefore, the results indicate that the proposed combined
      biofilm system is easy to operate and efficient for the treatment of high-ammonia
      wastewater.

PMID- 29595152
TI  - A new achievement in green degradation of aqueous organic pollutants under
      visible-light irradiation.
AB  - The global attention has been focused on degradation of the environmental organic
      pollutants through green methods such as advanced oxidation processes (AOPs)
      under sunlight. However, AOPs have not yet been efficient in function of the
      photocatalyst that has been used. In this work, firstly, CaCu3Ti4O12
      nanocomposite was simultaneously synthesized and decorated in different amounts
      of graphene oxide to enhance photodegradation of the organics. The result of the
      photocatalyst characterization showed that the sample with 8% graphene presented
      optimum photo-electrical properties such as low band gap energy and a great
      surface area. Secondly, the photocatalyst was applied for photodegradation of an
      organic model in a batch photoreactor. Thirdly, to scale up the process and
      optimize the efficiency, the photodegradation was modeled by multivariate semi
      empirical methods. As the optimized condition showed, 45 mg/L of the methyl
      orange has been removed at pH 5.8 by 0.96 g/L of the photocatalyst during 288 min
      of the light irradiation. Moreover, the photodegradation has been scaled up for
      industrial applications by determining the importance of the input effective
      variables according to the following organics order > photocatalyst > pH >
      irradiation time.

PMID- 29595153
TI  - Performance of a membrane bioreactor in extreme concentrations of bisphenol A.
AB  - In this study, a submerged membrane bioreactor was used to study the effect of
      low and high bisphenol A (BPA) concentration on the sludge biological activity.
      The pilot was operated over 540 days with hydraulic retention time and solid
      retention time of 5.5 hours and 140 days, respectively. As a hydrophobic
      compound, BPA was highly adsorbed by activated sludge. In lower concentrations,
      the biodegradation rate remained low, since the BPA concentration in the sludge
      was lower than 0.5 mg/g TS; yet, at an influent concentration up to 15 mg/L, the
      biodegradation rate was increasing, resulting in 99% BPA removal efficiency. The
      result for chemical oxygen demand removal showed that BPA concentration has no
      effect on the heterotrophic bacteria that were responsible for the organic carbon
      degradation. In higher concentrations, up to 16 mg of BPA was used for each gram
      of sludge as a source of carbon. However, the activity of autotrophic bacteria,
      including nitrifiers, was completely halted in the presence of 20 mg/L of BPA or
      more. Although nitrification was stopped after day 400, ammonia removal remained
      higher than 70% due to air stripping. Assimilation by bacteria was the only
      removal pathway for phosphorus, which resulted in an average 35% of P-PO4 removal
      efficiency.

PMID- 29595154
TI  - Domestic wastewater treatment by forward osmosis-membrane distillation (FO-MD)
      integrated system.
AB  - In this study, real domestic wastewater treatment by forward osmosis-membrane
      distillation (FO-MD) integrated system was investigated in laboratory scale. The
      integrated membrane system presented a good separation performance and the
      removal efficiency of most contaminants in the domestic wastewater was higher
      than 90%. High molecular weight contaminants were completely removed, while a few
      low molecular weight contaminants permeated through the membrane. The FO membrane
      fouling layer mainly consisted of organic substances like polysaccharides and
      proteins, and was very loose and could be effectively removed by rinsing the
      membrane surface with tap water. By comparison, the MD membrane fouling was
      mainly induced by inorganic salts and was not as severe as that of the FO
      membrane. During 120 h continuous operation, the FO-MD integrated system
      exhibited satisfying performance stability and maintained a high water yield and
      high product water quality. The results indicated the potential of the FO-MD
      integrated system for municipal wastewater treatment in coastal cities, water
      purification and desalination.

PMID- 29595155
TI  - Process optimization of CNP removal from industrial soft drink wastewater in a
      single up flow A2O with continuous feed and intermittent discharge regime.
AB  - Simultaneous removal of carbon and nutrients (CNP) in a single laboratory-scale
      bioreactor is advantageous in terms of reactor volume and energy consumption. In
      this study, an innovative up-flow anaerobic/anoxic/aerobic (A2O) single
      bioreactor with continuous feed and intermittent discharge (CFID) regime equipped
      with a movable aerator in the reactor height for simultaneous removal of CNP from
      soft drinks wastewater was successfully designed, fabricated and operated. The
      effects of four independent variables, i.e. hydraulic retention time (HRT),
      aerator height, biomass concentration and nitrogen/soluble chemical oxygen demand
      (N/sCOD) ratio at three levels in the range of 4-8 h, 37-55.5 cm, 4,000-6,000-1,
      and 0.05-0.2, respectively, on eight process responses were investigated. The
      central composite design (CCD) and response surface methodology (RSM) were
      applied to design the experimental conditions, model the obtained data, and
      optimize the process. The bioreactor provides three conditions with different
      dissolved oxygen (DO) (anaerobic, anoxic and aerobic) in a single bioreactor by
      placing the aerator in the middle of the reactor. As a result, the maximum sCOD,
      total nitrogen (TN) and total phosphorus (TP) removal were about 100, 92 and 41%,
      respectively. The optimum region obtained was an HRT of 5-11 h, a mixed liquor
      suspended solids (MLSS) concentration of 4,000-4,700 mgL-1, and an aerator height
      of 46.25 cm, at the N/sCOD ratio of 0.1.

PMID- 29595156
TI  - Structural characteristics of extracellular polymeric substances (EPS) in
      membrane bioreactor and their adsorptive fouling.
AB  - The soluble (S), loosely bound (LB) and tightly bound (TB) extracellular
      polymeric substances (EPS) were extracted from sludge flocs of a membrane
      bioreactor to evaluate their characteristics and adsorptive fouling. The degrees
      of adsorptive fouling by the EPS fractions were in the order S-EPS < TB-EPS < LB
      EPS. The images of atomic force microscopy showed the membrane fouled by LB-EPS
      was rougher than that fouled by the other fractions. The adsorbed EPS layer,
      which was sensed by quartz crystal microbalance with dissipation, was found to be
      more rigid and compact for LB-EPS, compared with the other EPS fractions. The
      excitation-emission matrix and Fourier transform infrared techniques were also
      used to characterize the individual EPS fractions. Compared with S-EPS and TB
      EPS, the LB-EPS contained a larger amount of aromatic protein and less
      carbohydrates and lipids, exhibiting characteristics of greater aromaticity and
      hydrophobicity. These characteristics should be responsible for more severe
      fouling, and the stiffer and more compact structure of the adsorbed layer.

PMID- 29595157
TI  - Removal of toxic metals using endocarp of acai berry as biosorbent.
AB  - The effectiveness of acai endocarp as biosorbent for removal of Cd2+, Pb2+ and
      Cr3+ from single solute solutions was analyzed. The biomass of acai endocarp was
      characterized by scanning electron microscopy, infrared spectroscopy and
      determining the point of zero charge. The optimum conditions for adsorption
      process were obtained at solution pH 6.0 for Cd(II) removal, pH 5.0 for Pb(II)
      removal, and, pH 4.0 for Cr(III). Furthermore, the average optimum efficiency of
      biosorbent in the optimum conditions was 8, 20 and 12 g of biosorbent per litre
      of contaminant solution, respectively, for Cd(II), Pb(II) and Cr(III). The best
      dynamic equilibrium time was reached at 60 min and Langmuir's model had the best
      fit for Cd(II) and Cr(III) biosorption, indicating a monolayer adsorption.
      Freundlich's model exhibited the best fit for Pb(II) ion. Elution rates were low,
      indicating a strong metal interaction with the adsorbent's surface. Thermodynamic
      parameters showed a spontaneous and endothermal process in the case of Cd(II) and
      Pb(II) ions, but not for Cr(III) ion, which appears to be an exothermic process.
      Results show that the use of the acai biosorbent may be a promising alternative
      for the remediation of polluted water, due to its low cost and highly
      availability.

PMID- 29595158
TI  - Optimization of the synthesis and operational parameters for NOM removal with
      response surface methodology during nano-composite membrane filtration.
AB  - The aim of this study was to investigate membrane synthesis by interfacial
      polymerization methods, the application of synthesized nano-composite membrane
      for natural organic matters (NOMs) removal from water, evaluation of fouling
      mechanism and antifouling properties. Polysulfone (PSf) was selected as a porous
      ultrafiltration membrane support and interfacial polymerization was done using
      tannic acid (TA) and Trimesoyl chloride (TMC) with central composite design
      (CCD). The effects of TA and TMC monomer concentrations, reaction time and post
      treatment temperature was evaluated. The synthesized membrane was characterized
      by field emission scanning electron microscope (FESEM), atomic force microscopy
      (AFM), attenuated total reflection Fourier transform infrared spectroscopy (ATR
      FTIR) and water contact angle. Based on the results, the optimum conditions for
      synthesizing nano-composite were: TA concentration of 0.27 g/L, TMC concentration
      of 0.22 g/L, reaction time of 68.29 min and temperature of 25.23  degrees C. The
      predicted optimum operational conditions were a NOM concentration of 6.429 mg/L;
      time of 10.931 min and applied pressure of 1.039 bar. The potential applications
      of the synthesized nano-composite membranes with interfacial polymerization can
      enhance water treatment.

PMID- 29595159
TI  - Polyacrylic acid grafted silica fume as an excellent adsorbent for
      dysprosium(III) removal from industrial wastewater.
AB  - In the development of industrial life, an enormous amount of silica fume (SF) has
      been accumulated and cannot be reused properly, and a large quantity of rare
      earth elements in industrial wastewater has been inappropriately discharged, both
      of which pose a threat to human health and the environment. By using UV
      photocatalytic grafting technology, a polymer brush grafted from modified SF,
      which can be used as a high efficiency adsorbent, can solve both problems at the
      same time. Specifically, SF was firstly silanol-functionalized by gamma
      methacryloxypropyltrimethoxysilane (KH570), then grafted with polyacrylic acid
      brushes by UV photocatalytic grafting to finally obtain the adsorbent. Under
      optimal conditions, adsorption capacity of the adsorbent for dysprosium(III)
      (Dy3+) could reach 278.49 mg/g. It took 1 min for the adsorbent to reach
      adsorbing equilibrium at a relatively low concentration of Dy3+ (40 mg/L), and
      only 3 min at a medium and high concentration (130 mg/L and 200 mg/L). After six
      adsorption-desorption cycles, the adsorbent still possessed high adsorption
      capacity for Dy3+ (251.20 mg/g). The adsorption behavior of the adsorbent fit the
      Langmuir isotherm model (R2 > 0.97) and pseudo-second-order kinetic model (R2 >
      0.98) well. The functional group of carboxylate anion, -COO-, played a central
      role during the adsorption process, which was verified by Fourier transform
      infrared and X-ray photoelectron spectroscopy analyses.

PMID- 29595160
TI  - Sequencing batch reactor process for the removal of nitrogen from anaerobically
      treated domestic wastewater.
AB  - This work presents the performance of a sequencing batch reactor (SBR) system
      used as a means of removing nitrogen from domestic wastewater containing a low
      chemical oxygen demand (COD) to nitrogen ratio due to pre-treatment with an
      anaerobic reactor. The aim of the work was to determine the feasibility of this
      system for the removal of nitrogen from the domestic wastewater. An SBR with a
      working volume of 5 L was investigated at different cycle times of 12, 8 and 6 h,
      at 18  degrees C. The efficiency of the SBR varied together with the duration of
      the cycle, where the optimum performance was seen in the 6 h cycle with the
      anoxic-aerobic-anoxic sequence. Due to the low quantity of organic matter present
      in the domestic wastewater after the anaerobic treatment, an additional supply of
      external carbon was necessary before the second anoxic stage. The removal
      efficiencies obtained were: 98% for total Kjeldahl nitrogen, 84% for total
      nitrogen and 77% for soluble COD. The reactor was thus shown to be viable, and it
      was concluded that this process may be successfully applied as a post-treatment
      for the removal of nitrogen from anaerobically treated domestic wastewater.

PMID- 29595161
TI  - Preparation of granular activated carbons from composite of powder activated
      carbon and modified beta-zeolite and application to heavy metals removal.
AB  - Heavy metals are continuously contaminating the surface and subsurface water. The
      adsorption process is an attractive alternative for removing the heavy metals
      because of its low cost, simple operation, high efficiency, and flexible design.
      In this study, influences of beta-zeolite and Cu-modified beta-zeolite on
      preparation of granular activated carbons (GACs) from a composite of powder
      activated carbon (PAC), methylcellulose as organic binder, bentonite as inorganic
      binder, and water were investigated. A number of granular samples were prepared
      by controlling the weight percentage of binder materials, PAC and zeolites as a
      reinforcing adsorbent. Fourier transform infrared spectroscopy (FT-IR) and X-ray
      diffraction techniques were employed to characterize zeolite, modified zeolite
      and produced GAC. The produced GACs were used as the adsorbent for removal of
      Zn+2, Cd2+ and Pb2+ ions from aqueous solutions. The results indicated that the
      adsorption of metals ions depended on the pH (5.5) and contact time (30 min).
      Maximum adsorption of 97.6% for Pb2+, 95.9% for Cd2+ and 91.1% for Zn+2 occurred
      with a new kind of GAC made of Cu-modified beta-zeolite. The Zn+2, Cd2+ and Pb2+
      ions sorption kinetics data were well described by a pseudo-second order model
      for all sorbents. The Langmuir and Freundlich isotherm models were applied to
      analyze the experimental equilibrium data.

PMID- 29595162
TI  - Exploring the potential of halophilic archaea for the decolorization of azo dyes.
AB  - Azo dyes are being extensively used in textile industries, so finding a proper
      solution to decolorize them is of high importance. In order to find azo dye
      decolorizing strains among haloarchaea, which are well known for their tolerance
      to harsh environmental conditions, fifteen haloarchaeal strains were screened.
      Halogeometricum sp. strain A and Haloferax sp. strain B with the highest
      decolorization ability (95% and 91% for Remazol black B; both about 60% for Acid
      blue 161, respectively) were selected for further studies. It was shown that both
      strains were able to grow and decolorize the dye in a medium containing up to 5 M
      NaCl, with optimum decolorization activity at 2.5-3.4 M, pH 7, and a wide
      temperature range between 30 to 45  degrees C. Moreover, both strains were able
      to tolerate and decolorize up to 1,000 mg l-1 Remazol black B. Also, they were
      able to survive in 5,000 mg l-1 of the dye after 20 days' incubation. Glucose and
      yeast extract were found to be the best carbon and nitrogen sources in the
      decolorization medium for both strains. This is the first report studying
      decolorization of azo dyes using halophilic archaea.

PMID- 29595163
TI  - Biosorption of cationic dyes by Para chestnut husk (Bertholletia excelsa).
AB  - Para chestnut husk (Bertholletia excelsa) (PCH), an agro-industrial waste largely
      generated in Brazil, was employed as a low-cost and efficient biosorbent to
      remove the cationic dyes Crystal Violet (CV) and Methylene Blue (MB) from aqueous
      media. PCH presented an amorphous structure containing carboxylic acids, esters,
      ketones and aldehydes on the surface. Non-porous and irregular particles were
      also observed. For both dyes, the biosorption capacity was favored under acid
      conditions. Equilibrium was attained within 40 min at 25  degrees C with a PCH
      dosage of 0.5 g L-1. The biosorption kinetic curves were satisfactory explained
      by the pseudo-first-order model. The Freundlich model was best for representing
      the equilibrium curves. The maximum biosorption capacities were 83.6 and 83.8 mg
      g-1 for CV and MB, respectively. PCH was efficient for treating a simulated
      textile effluent containing several dyes and chemicals, achieving a color removal
      of 90%. In this way, PCH can be considered as an option for treating colored
      effluents containing textile dyes.

PMID- 29595164
TI  - In situ remediation of hexavalent chromium contaminated soil by CMC-stabilized
      nanoscale zero-valent iron composited with biochar.
AB  - In this study, the remediation experiments were performed outdoors in natural
      conditions. Carboxymethyl cellulose (CMC)-stabilized nanoscale zero-valent iron
      (CMC-nZVI), biochar (BC) and CMC-stabilized nanoscale zero-valent iron composited
      with biochar (CMC-nZVI/BC) were synthesized and investigated for their effect on
      the in situ remediation of hexavalent chromium [Cr(VI)] contaminated soil and the
      concentration of available iron was tested after the remediation, compared with
      the untreated soil. The results of toxicity characteristic leaching procedure
      (TCLP) test showed that CMC-nZVI and CMC-nZVI/BC used as remediation materials
      could obviously improve the remediation rate of Cr contaminated soil and when the
      ratio of CMC-nZVI to Fe0 was 2.5 g/Kg, the leachability of Cr(VI) and Crtotal can
      be reduced by 100% and 95.8% simultaneously. Moreover, sequential extraction
      procedure (SEP) showed that most exchangeable Cr converted to carbonate-bound and
      Fe-Mn oxides-bound, reducing the availability and leachability of Cr in the soil.

PMID- 29595165
TI  - Assessing the impact of sea level rise due to climate change on seawater
      intrusion in Mekong Delta, Vietnam.
AB  - In the context of climate change, salinity intrusion into rivers has been, and
      will be, one of the most important issues for coastal water resources management.
      A combination of changes, including increased temperature, change in regional
      rainfall, especially sea level rise (SLR) related to climate change, will have
      significant impacts on this phenomenon. This paper presents the outcomes of a
      study conducted in the Mekong Delta of Vietnam (MKD) for evaluating the effect of
      sea water intrusion under a new SLR scenario. Salinity intrusion was simulated by
      one-dimensional (1D) modeling. The relative sea level projection was constructed
      corresponding to the RCP 6.0 emission scenario for MKD based on the statistical
      downscaling method. The sea level in 2050 is projected to increase from 25 cm to
      30 cm compared to the baseline period (in 2000). Furthermore, the simulated
      results suggested that salinity greater than 4 g/l, which affects rice yield,
      will intrude up to 50-60 km into the river. Approximately 30,000 ha of
      agricultural area will be affected if the sea level rise is 30 cm.

PMID- 29595166
TI  - Assessing the robustness of raingardens under climate change using SDSM and
      temporal downscaling.
AB  - Climate change is expected to lead to higher precipitation amounts and
      intensities causing an increase of the risk for flooding and combined sewer
      overflows in urban areas. To cope with these changes, water managers are
      requesting practical tools that can facilitate adaptive planning. This study was
      carried out to investigate how recent developments in downscaling techniques can
      be used to assess the effects of adaptive measures. A combined spatial-temporal
      downscaling methodology using the Statistical DownScaling Model-Decision Centric
      (SDSM-DC) and the Generalized Extreme Value distribution was applied to project
      future precipitation in the city of Bergen, Norway. A raingarden was considered a
      potential adaptive measure, and its performance was assessed using the RECARGA
      simulation tool. The benefits and limitations of using the proposed method have
      been demonstrated and compared to current design practices in Norway. Large
      differences in the raingarden's performance with respect to percentage overflow
      and lag-time reduction were found for varying projections. This highlights the
      need for working with a range of possible futures. Further, it was found that
      Ksat was the determining factor for peak-flow reduction and that different values
      of Ksat had different benefits. Engineering flexible solutions by combining
      measures holding different characteristics will induce robust adaptation.

PMID- 29595167
TI  - Oxidation of tartrazine with ultraviolet light emitting diodes: pH and duty
      cycles effects.
AB  - The presence of tartrazine (TAR) in the water cycle poses serious threats to
      human health. This study investigated the used of light emitting diodes (LEDs) in
      the advanced oxidation of TAR under different pH and duty cycle (DC) conditions.
      The first order reaction rate constant for TAR oxidation was positively
      correlated with DC, negatively correlated with pH, and typically greatest at pH
      6. Chemical byproduct analysis indicated that OH addition, H abstraction, and
      electron transfer without molecule transfer were among the relevant reaction
      mechanisms for TAR degradation. Six byproducts were identified, four were
      reported for the first time, and two demonstrated that TAR rings were cleaved.
      This research is the first to determine the optimal pH for UVLED-driven oxidation
      of TAR and the first to identify new TAR-related byproducts from UVLED-based
      water treatment.

PMID- 29595168
TI  - Formulation of a minimal nutritional medium for enhanced lipid productivity in
      Chlorella sp. and Botryococcus sp. using response surface methodology.
AB  - Chlorella sp. MCC 7 and Botryococcus sp. MCC 31 were investigated to enable large
      scale biodiesel production from minimal constituents in the growth medium.
      Response surface methodology (RSM) was used to maximise the biomass productivity
      and lipid yield using only nitrogen (N), phosphorus (P) and potassium (K) as
      urea, single super phosphate and muriate of potash. The optimum values were 0.42
      g/L nitrogen; 0.14 g/L phosphorus and 0.22 g/L potassium for Chlorella sp.; and
      0.46 g/L; 0.14 g/L and 0.25 g/L for Botryococcus sp. Lipid yield of 42% for
      Chlorella sp. and 52% in Botryococcus sp. was observed. An enhancement in lipid
      yield by approximately 55% for Chlorella sp. and 73% for Botryococcus sp. was
      registered as compared to original nutrient medium. Fourier transform infrared
      (FTIR) analysis of extracted lipids revealed characteristic bands for
      triglycerides. This study provided utilisation of a practicable nutrient recipe
      in the form of N, P, K input for enhanced lipid yield from the selected
      microalgal strains.

PMID- 29595169
TI  - Changes in estrogenicity and micropollutant concentrations across unit processes
      in a biological wastewater treatment system.
AB  - The behavior of 10 micropollutants, i.e. four estrogens (estrone, 17beta
      estradiol, estriol, 17alpha-ethynylestradiol), carbamazepine (CBZ),
      sulfamethoxazole (SMX), triclosan, oxybenzone, 4-nonylphenol, and bisphenol A,
      was investigated in a typical domestic wastewater treatment plant. LC-MS and
      yeast estrogen screen bioassay were used to study the changes in micropollutants
      and estrogenicity across unit processes in the treatment system. Primary
      treatment via sedimentation showed that only 4-nonylphenol was removed, but led
      to no significant change in estrogenicity. Secondary treatment by the biological
      nitrification-dentrification process showed complete removal of oxybenzone and
      partial removal of the estrogens, which led to a decrease in estrogenic activity
      from 80 to 48 ng/L as estradiol equivalent (EEq). Ultraviolet treatment
      completely degraded the estrogens and triclosan, but failed to lower the
      concentrations of bisphenol A, SMX, and CBZ; a decrease in estrogenic activity
      from 48 to 5 ng/L EEq across the unit, a value that was only slightly larger than
      the observed EEq of 1 ng/L for the deionized control. Similarly, the anaerobic
      digestion of sludge completely degraded estrogens, oxybenzone, and SMX, but had
      no impact on bisphenol A, triclosan, and CBZ. The study emphasises the need to
      complement chemical analyses with estrogenic bioassays to evaluate the efficacy
      of waste water treatment plants.

PMID- 29595170
TI  - The enhanced effect of activated sludge attached to the roots of Pistia
      stratiotes on nutrient removal for secondary effluent.
AB  - Aquatic plants are widely used for treating wastewater treatment plant secondary
      effluent. During this process, some residual activated sludge in the secondary
      effluent is intercepted and attaches to the plant roots. However, the effect of
      the attached activated sludge on nutrient removal in secondary effluent has up to
      now been unknown. Aiming at this problem, this investigation was conducted to
      compare the nutrient removal rates in secondary effluent by washed Pistia
      stratiotes (washed batch) and Pistia stratiotes with activated sludge attached to
      the roots (study batch). Extracellular polymeric substances (EPS) from the
      activated sludge attached to the roots were extracted and characterized by three
      dimensional excitation emission matrix (3D-EEM) fluorescence spectroscopy. The
      results showed that the nutrient removal rates in the study batch were better
      than that in the washed batch. The 3D-EEM results showed that the protein content
      of EPS increased during the experiment, indicating the growth of microorganisms
      in the attached activated sludge. Our work demonstrated the enhanced effect of
      activated sludge attached to the roots of Pistia stratiotes on the removal of
      pollutants in secondary effluent, which is useful to guide the practical
      engineering of secondary effluent treatment.

PMID- 29595171
TI  - Identifying critical components causing seasonal variation of activated sludge
      settleability and developing early warning tool.
AB  - Settleability of activated sludge is one of the most common problems that
      restricts the efficiency of activated sludge system. Obvious seasonal variation
      of settleability was found in the activated sludge system of a full scale
      wastewater treatment plant (WWTP) during 2 years of observation. Principal
      component analysis (PCA) was applied to study the correlation between diluted
      sludge volume index (DSVI), operational and environmental factors. As a result,
      temperature and mixed liquid suspended solids (MLSS) were found as the most
      significant variables relating with DSVI variation. Multivariate regression,
      partial least squares regression and support vector machine regression were
      applied to develop early warning models for DSVI prediction. The multivariate
      regression model was proved as a simple and easy-to-interpret early warning tool
      to be applied in practice. Based on the ratio of volatile substances in biomass,
      the original cause of seasonal variation of settleability was further discussed
      by referring the storage-biodegradation mechanism. Moreover, the results of this
      work also suggested that modern statistical techniques were important to
      investigate complicated engineering problems. This study provided insights of
      seasonal variation of activated sludge settleability by systematic investigation
      of long-term data of a full scale WWTP.

PMID- 29595172
TI  - Abundance and community structure of ammonia-oxidizing bacteria in activated
      sludge from different geographic regions in China.
AB  - Detailed ecological information on ammonia-oxidizing bacteria (AOB) in activated
      sludge of wastewater treatment plants (WWTPs) is very important to improve the
      efficiency of wastewater treatment. In this study, activated sludge samples were
      collected from seven municipal WWTPs located in seven cities in China, and real
      time quantitative polymerase chain reaction (qPCR), as well as construction of
      clone libraries combined with correlation-based data analysis was performed.
      Further, the effect of geographic distribution and some water quality parameters
      on the ecological distribution of AOB in activated sludge from WWTPs were
      investigated. The geographic distribution, the influent concentration of total
      nitrogen (TN) and ammonia nitrogen (NH4+-N) had significant effects on the
      abundance of AOB (P < 0.05). However, the community structure of AOB were not
      significantly affected by geographic distribution, but by water quality
      parameters including the concentrations of TN and NH4+-N. N. oligotropha lineage
      was the dominant AOB group in the wastewater treatment systems. The results
      obtained in this study provide useful information to understand some aspects of
      the ecological information and influencing factors of AOB in geographically
      distributed WWTPs.

PMID- 29595173
TI  - In situ continuous monitoring of nitrogen with ion-selective electrodes in a
      constructed wetland receiving treated wastewater: an operating protocol to obtain
      reliable data.
AB  - Constructed wetlands receiving treated wastewater (CWtw) are placed between
      wastewater treatment plants and receiving water bodies, under the perception that
      they increase water quality. A better understanding of the CWtw functioning is
      required to evaluate their real performance. To achieve this, in situ continuous
      monitoring of nitrate and ammonium concentrations with ion-selective electrodes
      (ISEs) can provide valuable information. However, this measurement needs
      precautions to be taken to produce good data quality, especially in areas with
      high effluent quality requirements. In order to study the functioning of a CWtw
      instrumented with six ISE probes, we have developed an appropriate methodology
      for probe management and data processing. It is based on an evaluation of
      performance in the laboratory and an adapted field protocol for calibration, data
      treatment and validation. The result is an operating protocol concerning an
      acceptable cleaning frequency of 2 weeks, a complementary calibration using CWtw
      water, a drift evaluation and the determination of limits of quantification (1
      mgN/L for ammonium and 0.5 mgN/L for nitrate). An example of a 9-month validated
      dataset confirms that it is fundamental to include the technical limitations of
      the measuring equipment and set appropriate maintenance and calibration
      methodologies in order to ensure an accurate interpretation of data.

PMID- 29595174
TI  - The formation of hybrid carbon nanomaterial by chemical vapor deposition: an
      efficient adsorbent for enhanced removal of methylene blue from aqueous solution.
AB  - In this study, carbon species were grown on the surface of Ni-impregnated powder
      activated carbon to form a novel hybrid carbon nanomaterial by chemical vapor
      deposition. The carbon nanomaterial was obtained by the precipitation of the
      methane elemental carbon atoms on the surface of the Ni catalyst. The
      physiochemical properties of the hybrid material were characterized to illustrate
      the successful growth of carbon species on the carbon substrate. The response
      surface methodology was used for the evaluation of adsorption parameters effect
      such as pH, adsorbent dose and contact time on the percentage removal of MB dye
      from aqueous solution. The optimum conditions were found to be pH = 11, adsorbent
      dose = 15 mg and contact time of 120 min. The material we prepared showed
      excellent removal efficiency of 96% for initial MB concentration of 50 mg/L. The
      adsorption of MB was described accurately by the pseudo-second-order model with
      R2 of 0.998 and qe of 163.93 (mg/g). The adsorption system showed the best
      agreement with Langmuir model with R2 of 0.989 and maximum adsorption capacity
      (Qm) of 250 mg/g.

PMID- 29595175
TI  - Modelling the effects of meteorological parameters on water temperature using
      artificial neural networks.
AB  - Water temperature affects all biological and chemical processes in water;
      therefore, it is an extremely important water quality parameter. Meteorological
      factors are among the most important factors that affect water temperatures. The
      aim of this study is to develop an artificial neural network (ANN) model to
      investigate the effects of meteorological parameters on water temperatures at
      Kizilirmak River in Turkey. Water temperature data were collected from gauging
      stations on Kizilirmak River, and meteorological data were acquired from the
      nearest meteorological stations. Air temperature, wind speed, relative humidity,
      and previous water temperatures were formed the input parameters. The model
      output included water temperatures. All data were available for the 1995-2007
      period, with occasional missing records. The activation functions of the ANN
      model and the number of neurons in the hidden layer were selected by trial-and
      error method to find the best results. The root mean square error and the
      correlation coefficient between observed and simulated water temperatures were
      used to assess the model success. The best results were obtained by using sigmoid
      activation function and scaled conjugate gradient algorithm. This study showed
      that meteorological data can be used to simulate water temperature with ANN model
      for Kizilirmak River.

PMID- 29595176
TI  - Decolourization of malachite green dye by mentha plant biochar (MPB): a combined
      action of adsorption and electrochemical reduction processes.
AB  - Adsorption behavior of mentha (mint) plant biochar (MPB) in removal of malachite
      green (MG) dye from aqueous solution was analyzed as a function of different pH
      (4.0-10.0), initial dye concentration (20-100 mg/L), contact time (0-45 min) and
      dose of adsorbent (0.05-0.3 g/100 mL). The zeta potential of the MPB particles
      was found to be -37.9 mV, indicating a negatively charged sorption surface of MPB
      particles. MPB was found to be more effective in removal of MG dye at pH 6.0 due
      to combined action of physico-chemisorption and a reductive electron transfer
      reaction. Results on the Brunauer-Emmett-Teller (BET) analysis of the N2
      adsorption-desorption isotherm of MPB as adsorbent showed sigmoidal shape similar
      to the type IV isotherm and mesoporous nature. The cyclic voltammetric analysis
      of MG dye showed a reversible, coupled redox reaction at the interface of dye
      molecules and MPB particles. The maximum monolayer adsorption capacity (qmax) of
      MPB was found to be 322.58 mg g-1. The separation factor (RL) value was between 0
      and 1, indicating a favourable adsorption of MG dye onto MPB. The results fitted
      well to a pseudo-second-order kinetic model. Further results from desorption
      experiments showed recovery of MG dye by about 50% in the presence of 1 N HCl.

PMID- 29595177
TI  - Effect of water-to-cement ratio and curing method on the strength, shrinkage and
      slump of the biosand filter concrete body.
AB  - The biosand filter is a household-level water treatment technology used globally
      in low-resource settings. As of December 2016, over 900,000 biosand filters had
      been implemented in 60 countries around the world. Local, decentralized
      production is one of the main advantages of this technology, but it also creates
      challenges, especially in regards to quality control. Using the current
      recommended proportions for the biosand filter concrete mix, slump was measured
      at water-to-cement ratios of 0.51, 0.64 and 0.76, with two replicates for each
      level. Twenty-eight-day strength was tested on four replicate cylinders, each at
      water-to-cement ratios of 0.51, 0.59, 0.67 and 0.76. Wet curing and dry curing
      were compared for 28-day strength and for their effect on shrinkage. Maximum
      strength occurred at water-to-cement ratios of 0.51-0.59, equivalent to 8-9.3 L
      water for a full-scale filter assuming saturated media, corresponding to a slump
      class of S1 (10-40 mm). Wet curing significantly improved strength of the
      concrete mix and reduced shrinkage. Quality control measures such as the slump
      test can significantly improve the quality within decentralized production of
      biosand filters, despite localized differences in production conditions.

PMID- 29595178
TI  - Relevance of n-butanol as a reference gas for odorants and complex odors.
AB  - Odor analysis by olfactometry relies on the use of n-butanol as a reference
      compound for standardizing the selection of human panelists. This requires that
      human sensitivity towards n-butanol is correlated to sensitivity towards other
      odorants as well as complex odor mixtures. However, there is limited evidence in
      the literature of such correlations. In this work, datasets from three odor
      laboratories were investigated in order to clarify this. All panels routinely
      analyzed n-butanol and H2S samples. Two of the laboratories analyzed samples from
      pig production or industry, whereas one laboratory determined odor threshold
      values for typical pig production odorants. Non-significant correlations were
      observed in most cases and odor threshold values for structurally related
      compounds were not well correlated. The work presented strongly indicates that
      the sensitivity of odor panelists towards n-butanol is not well transferred to
      other odorants or odor samples. Furthermore, minimization of variance by using n
      butanol is not transferable to other odorants or environmental samples. Thus, the
      harmonization of human panelists for odor analysis based on n-butanol does not
      appear to result in harmonization with respect to other odorants or odor samples.

PMID- 29595179
TI  - Attribute-based intervention development for increasing resilience of urban
      drainage systems.
AB  - Resilience building commonly focuses on attributes such as redundancy. Whilst
      this may be effective in some cases, provision of specific attributes does not
      guarantee resilient performance and research is required to determine the
      suitability of such approaches. This study uses 250 combined sewer system virtual
      case studies to explore the effects of two attribute-based interventions
      (increasing distributed storage and reducing imperviousness) on performance-based
      resilience measures. These are found to provide improvement in performance under
      system failure in the majority of case studies, but it is also shown that
      attribute-based intervention development can result in reduced resilience.

PMID- 29595180
TI  - Application of electrochemical peroxidation (ECP) process for waste-activated
      sludge stabilization and system optimization using response surface methodology
      (RSM).
AB  - In this study, the performance of the electrochemical peroxidation (ECP) process
      for removing the volatile suspended solids (VSS) content of waste-activated
      sludge was evaluated. The Fe2+ ions required by the process were obtained
      directly from iron electrodes in the system. The performance of the ECP process
      was investigated in various operational conditions employing a laboratory-scale
      pilot setup and optimized by response surface methodology (RSM). According to the
      results, the ECP process showed its best performance when the pH value, current
      density, H2O2 concentration and the retention time were 3, 3.2 mA/cm2, 1,535 mg/L
      and 240 min, respectively. In these conditions, the introduced Fe2+ concentration
      was approximately 500 (mg/L) and the VSS removal efficiency about 74%. Moreover,
      the results of the microbial characteristics of the raw and the stabilized sludge
      demonstrated that the ECP process is able to remove close to 99.9% of the
      coliforms in the raw sludge during the stabilization process. The energy
      consumption evaluation showed that the required energy of the ECP reactor (about
      1.8-2.5 kWh (kg VSS removed)-1) is considerably lower than for aerobic digestion,
      the conventional waste-activated sludge stabilization method (about 2-3 kWh (kg
      VSS removed)-1). The RSM optimization process showed that the best operational
      conditions of the ECP process comply with the experimental results, and the
      actual and the predicted results are in good conformity with each other. This
      feature makes it possible to predict the introduced Fe2+ concentrations into the
      system and the VSS removal efficiency of the process precisely.

PMID- 29595181
TI  - Case report of ventral hernia complicating bariatric surgery.
AB  - Ventral hernias (VHs) are common in the bariatric population with incidence of
      around 8% of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB).
      The factors contributing to the incidence of VH includes high intra-abdominal
      pressures, previous histories of abdominal surgeries, defects in fascial
      structure and reduced healing tendency. There is a high index of suspicion in BS
      patients with VH for hernia complications which can be lethal after LRYGB. Here,
      we present a case where VH complicated the LRYGB surgery.

PMID- 29595182
TI  - C-reactive protein as predictor of anastomotic complications after minimally
      invasive oesophagectomy.
AB  - Background: Anastomotic leaks after oesophagectomy with tabularised stomach
      replacement are a significant factor in post-operative mortality and morbidity.
      Early detection and treatment of this complication allow for improving operative
      and oncological results. When assessing laboratory values - elevation of
      inflammatory parameters - complicated interpretation is an issue (systemic
      inflammatory response syndrome, surgical versus non-surgical complication).
      Results studying the relationship between C-reactive protein (CRP) and
      complications following oesophagectomies are inconsistent. The aim of our work
      was to find relationships between the development of post-operative CRP values
      and the occurrence of anastomotic complications following minimally invasive
      oesophagectomy (MIE). Materials and Methods: Analysis of the relationship between
      CRP values and the occurrence of anastomotic complications or the necessity of
      reoperation following oesophagectomy with tabularised stomach replacement and
      cervical anastomosis performed using thoracoscopy and laparoscopy in a group of
      patients operated on for malignancies at our department between 2012 and 2015.
      Results: A significant difference was found in average CRP values on the 5th day
      and 7th day following operation between patients with and without leaks (233 mg/l
      vs. 122.8 mg/l P = 0.003, respectively 208.9 mg/l vs. 121.3 mg/l P = 0.014).
      However, on the 5th day, the leak was clinically apparent only in one case out of
      11 leaks. A significant difference in CRP values on the 5th day was found between
      patients who needed revision surgery and patients without revision surgery (294
      mg/l vs. 133.5 mg/l P = 0.01). Conclusions: Patients after MIE with tabularised
      stomach replacement and cervical anastomosis complicated by anastomotic leaks or
      with the necessity for reoperation had a significantly higher CRP values on the
      5th day following operation than patients without complications, regardless of
      the presence of clinical signs of leaks.

PMID- 29595183
TI  - Gastrointestinal stromal tumours of stomach: Robot-assisted excision with the da
      Vinci Surgical System regardless of size and location site.
AB  - AIMS: The role of minimally invasive surgery of gastrointestinal stromal tumours
      (GISTs) of the stomach remains uncertain especially for large and/or difficult
      located tumours. We are hereby presenting a single-centre series of robot
      assisted resections using the da Vinci Surgical System (Si or Xi). SUBJECTS AND
      METHODS: Data of patients undergoing robot-assisted treatment of gastric GIST
      were retrieved from the prospectively collected institutional database and a
      retrospective analysis was performed. Patients were stratified according to size
      and location of the tumour. Difficult cases (DCs) were considered for size if
      tumour was> 50 mm and/or for location if the tumour was Type II, III or IV sec.
      Privette/Al-Thani classification. RESULTS: Between May 2010 and February 2017, 12
      consecutive patients underwent robot-assisted treatment of GIST at our
      institution. DCs were 10/12 cases (83.3%), of which 6/10 (50%) for location, 2/10
      (25%) for size and 2/10 (25%) for both. The da Vinci Si was used in 8 patients,
      of which 6 (75%) were DC, and the da Vinci Xi in 4, all of which (100%) were DC.
      In all patients, excision was by wedge resection. All lesions had microscopically
      negative resection margins. There was no conversion to open surgery, no tumour
      ruptures or spillage and no intraoperative complications. CONCLUSION: Our
      experience suggests a positive role of the robot da Vinci in getting gastric GIST
      removal with a conservative approach, regardless of size and location site.
      Comparative studies with a greater number of patients are necessary for a more
      robust assessment.

PMID- 29595184
TI  - Genetic and molecular aspects of androgenetic alopecia.
AB  - Androgenetic alopecia is the most common form of progressive hair loss in humans.
      A genetic predisposition and hormonal status are considered as major risk factors
      for this condition. Several recent advances in molecular biology and genetics
      have increased our understanding of the mechanisms of hair loss in androgenetic
      alopecia. We review these advances and examine the trends in the genetic and
      molecular aspects of androgenetic alopecia.

PMID- 29595185
TI  - Acute Respiratory Distress Syndrome: Challenge for Diagnosis and Therapy.
AB  - Objective: Acute respiratory distress syndrome (ARDS) is a devastating clinical
      syndrome whose diagnosis and therapy are still in question. The aim of this
      review was to discuss the current challenge for the diagnosis and treatment of
      ARDS. Data Sources: Data sources were the published articles in English through
      December 2017 in PubMed using the following key words: "acute respiratory
      distress syndrome," "definition", "diagnosis," "therapy," "lung protective
      strategy," "right ventricular dysfunction," and "molecular mechanism." Study
      Selection: The selection of studies focused on both preclinical studies and
      clinical studies of therapy of ARDS. Results: The incidence of ARDS is still
      high, and ARDS causes high intensive care units admissions and high mortality.
      The Berlin Definition proposed in 2012 is still controversial owing to lack of
      sensitivity and specificity. ARDS is still under recognition and it is associated
      with high mortality. Lung protective strategies with low tidal volume (VT) and
      lung recruitment should consider the physiology of ARDS because ARDS presents
      lung inhomogeneity; the same low VT might increase local stress and strain in
      some patients with low compliance, and lung recruitment could injure lungs in
      ARDS patients with low recruitability and hemodynamic instability. Acute cor
      pulmonale is common in severe ARDS. ARDS itself and some treatments could worsen
      acute cor pulmonale. Molecular understanding of the pathogenic contributors to
      ARDS has improved, but the molecular-associated treatments are still under
      development. Conclusions: ARDS is a devastating clinical syndrome whose incidence
      and mortality has remained high over the past 50 years. Its definition and
      treatments are still confronted with challenges, and early recognition and
      intervention are crucial for improving the outcomes of ARDS. More clinical
      studies are needed to improve early diagnosis and appropriate therapy.

PMID- 29595186
TI  - Evaluation of the Patterns of Non-Adherence to Anti-Platelet Regimens in Stented
      Patients Bleeding Score for Predicting the Long-term Out-of-hospital Bleeding
      Risk in Chinese Patients after Percutaneous Coronary Intervention.
AB  - Background: The Patterns of Non-Adherence to Anti-Platelet Regimens in Stented
      Patients (PARIS) bleeding score is a novel score for predicting the out-of
      hospital bleeding risk after percutaneous coronary intervention (PCI). However,
      whether this score has the same value in non-European and American populations is
      unclear. This study aimed to assess the PARIS bleeding score's predictive value
      of bleeding in patients after PCI in the Chinese population. Methods: We
      performed a prospective, observational study of 10,724 patients who underwent PCI
      from January to December 2013, in Fuwai Hospital, China. We defined the primary
      end point as major bleeding (MB) according to Bleeding Academic Research
      Consortium definition criteria including Type 2, 3, or 5. The predictive value of
      the PARIS bleeding score was assessed with the area under the receiver operating
      characteristic (AUROC) curve. Results: Of 9782 patients, 245 (2.50%) MB events
      occurred during the 2 years of follow-up. The PARIS bleeding score was
      significantly higher in the MB group than that of non-MB group (4.00 [3.00, 5.00]
      vs. 3.00 [2.00, 5.00], Z = 3.71, P < 0.001). According to risk stratification of
      the PARIS bleeding score, the bleeding risk in the intermediate- and high-risk
      groups was 1.50 times (hazard ratio [HR]: 1.50; 95% confidence interval [CI]:
      1.160-1.950; P = 0.002) and 2.27 times higher (HR: 2.27; 95% CI: 1.320-3.900; P =
      0.003) than that in the low-risk group. The PARIS bleeding score showed a
      moderate predictive value for MB in the overall population (AUROC: 0.568, 95% CI:
      0.532-0.605; P < 0.001) and acute coronary syndrome (ACS) subgroup (AUROC: 0.578,
      95% CI: 0.530-0.626; P = 0.001) and tended to be predictive in the non-ACS
      subgroup (AUROC: 0.556, 95% CI: 0.501-0.611; P = 0.054). Conclusion: The PARIS
      bleeding score shows good clinical value for risk stratification and has a
      significant, but relatively limited, prognostic value for out-of-hospital
      bleeding in the Chinese population after PCI.

PMID- 29595187
TI  - Inhibition of Expression of the S100A8 Gene Encoding the S100 Calcium-Binding
      Protein A8 Promotes Apoptosis by Suppressing the Phosphorylation of Protein
      Kinase B (Akt) in Endometrial Carcinoma and HEC-1A Cells.
AB  - BACKGROUND The aim of this study was to investigate the expression and silencing
      of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8),
      and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of
      endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro.
      MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of
      the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal
      endometrial tissue samples. A stable S100A8 gene knockdown cell line was
      constructed using lentiviral packing short hairpin RNA (shRNA) transfected into
      HEC-1A cells. S100A8 mRNA and S100A8 protein levels were detected by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting.
      The effects of expression of the S100A8 gene by endometrial cancer cells was
      investigated by the MTT assay, cell cycle and apoptotic assays, qRT-PCR, and
      Western blotting. RESULTS IHC showed high levels of expression of S100A8 protein
      in endometrial carcinoma tissues, and HEC-1A adenocarcinoma cells (in G1 and G2).
      Increased expression of S100A8 protein was found endometrial cancer tissues
      compared with normal endometrial tissues (79.7% vs. 4.5%). S100A8 gene knockdown
      reduced cell proliferation in the HEC-1A cells compared with control cells,
      induced cell apoptosis, inhibited the phosphorylation of protein kinase B (Akt),
      and induced the expression of pro-apoptotic genes, including the cytochrome C
      gene, CYCS, BAD, BAX, FOXO1, FOXO3, CASP9, and CASP3. CONCLUSIONS In endometrial
      carcinoma cells, down-regulation of the S100A8 gene induced cell apoptosis via
      inhibition of the phosphorylated or active form of protein kinase B (Akt).

PMID- 29595188
TI  - Publisher Correction: Base excision repair AP endonucleases and mismatch repair
      act together to induce checkpoint-mediated autophagy.
AB  - This corrects the article DOI: 10.1038/ncomms3674.

PMID- 29595189
TI  - Publisher Correction: Observation of dark states in a superconductor diamond
      quantum hybrid system.
AB  - This corrects the article DOI: 10.1038/ncomms4524.

PMID- 29595190
TI  - Functions and the related signaling pathways of the neurotrophic factor neuritin.
AB  - Neuritin is a member of the neurotrophic factor family, which is activated by
      neural activity and neurotrophins, and promotes neurite growth and branching. It
      has shown to play an important role in neuronal plasticity and regeneration. It
      is also involved in other biological processes such as angiogenesis,
      tumorigenesis and immunomodulation. Thus far, however, the primary mechanisms of
      neuritin, including whether or not it acts through a receptor or which downstream
      signals might be activated following binding, are not fully understood. Recent
      evidence suggests that neuritin may be a potential therapeutic target in several
      neurodegenerative diseases. This review focuses on the recent advances in studies
      regarding the newly identified functions of neuritin and the signaling pathways
      related to these functions. We also discuss current hot topics and difficulties
      in neuritin research.

PMID- 29595192
TI  - Blockade of the swelling-induced chloride current attenuates the mouse neonatal
      hypoxic-ischemic brain injury in vivo.
AB  - Activation of swelling-induced Cl- current (ICl,swell) during neonatal hypoxia
      ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes
      chronic neurological morbidity in neonates as well as acute mortality. In this
      study, we investigated the role of ICl,swell in hypoxic-ischemic brain injury
      using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)
      oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30%
      hypotonic solution activated ICl,swell, which was completely blocked by the
      application of DCPIB (10 MUmol/L). The role of ICl,swell in neonatal hypoxic
      ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic
      ischemic brain injury model. Before receiving the ischemic insult, the mouse pups
      were injected with DCPIB (10 mg/kg, ip). We found that pretreatment with DCPIB
      significantly reduced the brain damage assessed using TTC staining, Nissl
      staining and whole brain imaging, and improved the sensorimotor and vestibular
      recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and
      cliff avoidance reflex). These results show that DCPIB has neuroprotective
      effects on neonatal hypoxic-ischemic brain injury, and that the ICl,swell may
      serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy.

PMID- 29595194
TI  - Publisher Correction: Identification of a splice variant of mouse TRPA1 that
      regulates TRPA1 activity.
AB  - This corrects the article DOI: 10.1038/ncomms3399.

PMID- 29595193
TI  - Xyloketal B exerts antihypertensive effect in renovascular hypertensive rats via
      the NO-sGC-cGMP pathway and calcium signaling.
AB  - Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus
      Xylaria sp. (No 2508). We previously showed that Xyl-B promoted endothelial NO
      release and protected against atherosclerosis through the Akt/eNOS pathway.
      Vascular NO production regulates vasoconstriction in central and peripheral
      arteries and plays an important role in blood pressure control. In this study, we
      examined whether Xyl-B exerted an antihypertensive effect in a hypertensive rat
      model, and further explored the possible mechanisms underlying its
      antihypertensive action. Administration of Xyl-B (20 mg.kg-1.d-1, ip, for 12
      weeks) significantly decreased the systolic and diastolic blood pressure in a two
      kidney, two-clip (2K2C) renovascular hypertensive rats. In endothelium-intact and
      endothelium-denuded thoracic aortic rings, pretreatment with Xyl-B (20 MUmol/L)
      significantly suppressed phenylephrine (Phe)-induced contractions, suggesting
      that its vasorelaxant effect was attributed to both endothelial-dependent and
      endothelial-independent mechanisms. We used SNP, methylene blue (MB, guanylate
      cyclase inhibitor) and indomethacin (IMC, cyclooxygenase inhibitor) to examine
      which endothelial pathway was involved, and found that MB, but not IMC, reversed
      the inhibitory effects of Xyl-B on Phe-induced vasocontraction. Moreover, Xyl-B
      increased the endothelial NO bioactivity and smooth muscle cGMP level, revealing
      that the NO-sGC-cGMP pathway, rather than PGI2, mediated the anti-hypertensive
      effect of Xyl-B. We further showed that Xyl-B significantly attenuated KCl
      induced Ca2+ entry in smooth muscle cells in vitro, which was supposed to be
      mediated by voltage-dependent Ca2+ channels (VDCCs), and reduced ryanodine
      induced aortic contractions, which may be associated with store-operated Ca2+
      entry (SOCE). Taken together, these findings demonstrate that Xyl-B exerts
      significant antihypertensive effects not only through the endothelial NO-sGC-cGMP
      pathway but also through smooth muscle calcium signaling, including VDCCs and
      SOCE.

PMID- 29595195
TI  - Publisher Correction: Probing the nature of gold-carbon bonding in gold-alkynyl
      complexes.
AB  - This corrects the article DOI: 10.1038/ncomms3223.

PMID- 29595191
TI  - Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral
      ischemia-reperfusion injuries: potential application for drug discovery.
AB  - Reactive nitrogen species (RNS) play important roles in mediating cerebral
      ischemia-reperfusion injury. RNS activate multiple signaling pathways and
      participate in different cellular events in cerebral ischemia-reperfusion injury.
      Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP)
      are important signaling molecules in the pathological process of ischemic brain
      injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO)
      and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression
      of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS)
      to promote RNS generation. The increased RNS further induce MMP activation and
      mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage
      in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction
      among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic
      brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav
      1/MMP pathway could be a promising therapeutic strategy for protecting against
      cerebral ischemia-reperfusion injury. In this mini-review article, we highlight
      the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke
      injury and review the current progress of studies seeking therapeutic compounds
      targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia
      reperfusion injury. Several representative natural compounds, including calycosin
      7-O-beta-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP),
      chlorogenic acid, lutein and lycopene, have shown potential for targeting the
      RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke.
      Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in
      ischemic stroke treatment.

PMID- 29595196
TI  - Editors' note: Omitting obesity treatment leads to poor outcomes, even in those
      who appear to be metabolically healthy.

PMID- 29595198
TI  - Correction: Clinical applications of infrared and Raman spectroscopy: state of
      play and future challenges.
AB  - Correction for 'Clinical applications of infrared and Raman spectroscopy: state
      of play and future challenges' by Matthew J. Baker, et al., Analyst, 2018, DOI:
      10.1039/c7an01871a.

PMID- 29595197
TI  - Antimicrobial action of the cationic peptide, chrysophsin-3: a coarse-grained
      molecular dynamics study.
AB  - Antimicrobial peptides (AMPs) are small cationic proteins that are able to
      destabilize a lipid bilayer structure through one or more modes of action. In
      this study, we investigate the processes of peptide aggregation and pore
      formation in lipid bilayers and vesicles by the highly cationic AMP, Chrysophsin
      3 (chrys-3), using coarse-grained molecular dynamics (CG-MD) simulations and
      potential of mean force calculations. We study long 50 MUs simulations of chrys-3
      at different concentrations, both at the surface of
      dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylcholine
      (POPC) bilayers, and also interacting within the interior of the lipid membrane.
      We show that aggregation of peptides at the surface, leads to pronounced
      deformation of lipid bilayers, leading in turn to lipid protrusions for peptide :
      ligand ratios > 1 : 12. In addition, aggregation of chrys-3 peptides within the
      centre of a lipid bilayer leads to spontaneous formation of pores and aggregates.
      Both mechanisms of interaction are consistent with previously reported
      experimental data for chrys-3. Similar results are observed also in POPC vesicles
      and mixed lipid bilayers composed of the zwitterionic lipid
      palmitoyloleoylphosphatidylethanolamine (POPE) and the negatively charged lipid
      palmitoyloleoylphosphatidylglycerol (POPG). The latter are employed as models of
      the bacterial membrane of Escherichia coli.

PMID- 29595199
TI  - Monodisperse CoSn2 and FeSn2 nanocrystals as high-performance anode materials for
      lithium-ion batteries.
AB  - Nanostructured metal alloys show great promise as replacement materials for
      graphite anodes, and could improve the energy and power density of present-day
      lithium-ion batteries (LIBs). Herein, we report a facile colloidal synthesis of
      CoSn2 and FeSn2 nanocrystals (NCs) via the reaction of Co or Fe NCs and SnCl2 in
      oleylamine under reducing conditions. Among our pure Sn NCs and mixtures of Co or
      Fe and Sn NCs, monodisperse CoSn2 nanoalloys showed considerably improved cycling
      stability. In particular, CoSn2 delivered a stable average capacity of 650 mA h g
      1 for 5000 cycles at a high current density of 1984 mA g-1, which is among the
      highest reported cycling stabilities for Sn-based anode materials.

PMID- 29595200
TI  - Hyperpolarized long-lived nuclear spin states in monodeuterated methyl groups.
AB  - Monodeuterated methyl groups may support a long-lived nuclear spin state, with a
      relaxation time exceeding the conventional spin-lattice relaxation time T1.
      Dissolution-DNP (dynamic nuclear polarization) may be used to hyperpolarize such
      a long-lived spin state. This is demonstrated for the CH2D groups of a piperidine
      derivative. The polarized sample is manipulated in the ambient magnetic field of
      the laboratory, without destruction of the hyperpolarized singlet order. Strongly
      enhanced CH2D signals are observed more than one minute after dissolution, even
      in the presence of paramagnetic radicals, by which time the NMR signal from the
      hyperpolarized proton magnetization has completely disappeared.

PMID- 29595201
TI  - A genetically encoded 19F NMR probe for lysine acetylation.
AB  - Advances in acetylated protein-protein/DNA interactions depend on the development
      of a novel NMR (nuclear magnetic resonance) probe to study the conformational
      changes of acetylated proteins. However, the method for detecting the acetylated
      protein conformation is underdeveloped. Herein, an acetyllysine mimic has been
      exploited for detecting the conformational changes of acetylated p53-protein/DNA
      interactions by genetic code expansion and 19F NMR. This 19F NMR probe shows high
      structural similarity to acetyllysine and could not be deacetylated by sirtuin
      deacetylase in vitro/vivo. Moreover, acetylation of p53 K164 is reported to be
      deacetylated by SIRT2 for the first time.

PMID- 29595202
TI  - Mining legacy across a wetland landscape: high mercury in Upper Peninsula
      (Michigan) rivers, lakes, and fish.
AB  - A geographic enigma is that present-day atmospheric deposition of mercury in the
      Upper Peninsula of Michigan is low (48%) and that regional industrial emissions
      have declined substantially (ca. 81% reduction) relative to downstate. Mercury
      levels should be declining. However, state (MDEQ) surveys of rivers and lakes
      revealed elevated total mercury (THg) in Upper Peninsula waters and sediment
      relative to downstate. Moreover, Western Upper Peninsula (WUP) fish possess
      higher methyl mercury (MeHg) levels than Northern Lower Peninsula (NLP) fish. A
      contributing explanation for elevated THg loading is that a century ago the Upper
      Peninsula was a major industrial region, centered on mining. Many regional ores
      (silver, copper, zinc, massive sulfides) contain mercury in part per million
      concentrations. Copper smelters and iron furnace-taconite operations broadcast
      mercury almost continuously for 140 years, whereas mills discharged tailings and
      old mine shafts leaked contaminated water. We show that mercury emissions from
      copper and iron operations were substantial (60-650 kg per year) and dispersed
      over relatively large areas. Moreover, lake sediments in the vicinity of mining
      operations have higher THg concentrations. Sediment profiles from the Keweenaw
      Waterway show that THg accumulation increased 50- to 400-fold above modern-day
      atmospheric deposition levels during active mining and smelting operations, with
      lingering MeHg effects. High MeHg concentrations are geographically correlated
      with low pH and dissolved organic carbon (DOC), a consequence of biogeochemical
      cycling in wetlands, characteristic of the Upper Peninsula. DOC can mobilize
      metals and elevate MeHg concentrations. We argue that mercury loading from mining
      is historically superimposed upon strong regional wetland effects, producing a
      combined elevation of both THg and MeHg in the Western Upper Peninsula.

PMID- 29595203
TI  - nCVTs: a hybrid smart tumour targeting platform.
AB  - A hybrid drug delivery platform involving the fusion of cell membranes from U937
      monocytes and synthetic lipids to create nano-cell vesicle technology systems
      (nCVTs) is designed. nCVTs are engineered for a targeted approach towards tumour
      sites by preserving key surface proteins from U937 monocytes, while being
      amendable to functionalization and loading due to their liposomal components.

PMID- 29595204
TI  - Three-dimensional carbon network confined antimony nanoparticle anodes for high
      capacity K-ion batteries.
AB  - Antimony (Sb) represents a promising anode for K-ion batteries (KIBs) due to its
      high theoretical capacity and suitable working voltage. However, the large volume
      change that occurs in the potassiation/depotassiation process can lead to severe
      capacity fading. Herein, we report a high-capacity anode material by in situ
      confining Sb nanoparticles in a three-dimensional carbon framework (3D SbNPs@C)
      via a template-assisted freeze-drying treatment and subsequent carbothermic
      reduction. The as-prepared 3D SbNPs@C hybrid material delivers high reversible
      capacity and good cycling stability when used as the anode for KIBs. Furthermore,
      cyclic voltammetry and in situ X-ray diffraction analysis were performed to
      reveal the intrinsic mechanism of a K-Sb alloying reaction. Therefore, this work
      is of great importance to understand the electrochemical process of the Sb-based
      alloying reaction and will pave the way for the exploration of high performance
      KIB anode materials.

PMID- 29595205
TI  - Correction: A high quality liquid-type quantum dot white light-emitting diode.
AB  - Correction for 'A high quality liquid-type quantum dot white light-emitting
      diode' by Chin-Wei Sher et al., Nanoscale, 2016, 8, 1117-1122.

PMID- 29595210
TI  - Recyclable cellulose-palladium nanoparticles for clean cross-coupling chemistry.
AB  - Cheap, recyclable, and robust cellulose-palladium nanoparticles were developed
      and fully characterized by FTIR, TEM, XPS, TGA, and NMR. The nanoparticles
      enabled cross-coupling chemistry in a truly general fashion i.e., Suzuki-Miyaura,
      Heck, Sonogashira, and C-H activation. Notably, all types of transformations were
      achieved with a single type of nanocatalyst. Complete recyclability of the
      catalyst and low traces of palladium in the product demonstrates the greenness of
      the protocol.

PMID- 29595211
TI  - Correction: A smart pH-responsive nano-carrier as a drug delivery system for the
      targeted delivery of ursolic acid: suppresses cancer growth and metastasis by
      modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways.
AB  - Correction for 'A smart pH-responsive nano-carrier as a drug delivery system for
      the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by
      modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways' by Kai Jiang
      et al., Nanoscale, 2017, 9, 9428-9439.

PMID- 29595215
TI  - Corrigenda.

PMID- 29595216
TI  - Corrigenda.

PMID- 29595213
TI  - Guiding 3D cell migration in deformed synthetic hydrogel microstructures.
AB  - The ability of cells to navigate through the extracellular matrix, a network of
      biopolymers, is controlled by an interplay of cellular activity and mechanical
      network properties. Synthetic hydrogels with highly tuneable compositions and
      elastic properties are convenient model systems for the investigation of cell
      migration in 3D polymer networks. To study the impact of macroscopic deformations
      on single cell migration, we present a novel method to introduce uniaxial strain
      in matrices by microstructuring photo-polymerizable hydrogel strips with embedded
      cells in a channel slide. We find that such confined swelling results in a
      strained matrix in which cells exhibit an anisotropic migration response parallel
      to the strain direction. Surprisingly, however, the anisotropy of migration
      reaches a maximum at intermediate strain levels and decreases strongly at higher
      strains. We account for this non-monotonic response in the migration anisotropy
      with a computational model, in which we describe a cell performing durotactic and
      proteolytic migration in a deformable elastic meshwork. Our simulations reveal
      that the macroscopically applied strain induces a local geometric anisotropic
      stiffening of the matrix. This local anisotropic stiffening acts as a guidance
      cue for directed cell migration, resulting in a non-monotonic dependence on
      strain, as observed in our experiments. Our findings provide a mechanism for
      mechanical guidance that connects network properties on the cellular scale to
      cell migration behaviour.

PMID- 29595217
TI  - Extended patch-test screening for fragrance contact allergy: findings and
      challenges.

PMID- 29595218
TI  - Image Gallery: Transition pattern in acral melanoma.

PMID- 29595219
TI  - By using a core outcome set we measure what matters to patients.

PMID- 29595220
TI  - Image Gallery: Symmetric reticular scarring of the cheeks.

PMID- 29595221
TI  - Image Gallery: Contact dermatitis resulting from tarantula-hair injury mimicking
      ischaemia: a case with dermoscopy follow-up.

PMID- 29595223
TI  - Corrigenda.

PMID- 29595222
TI  - Cause or consequence? Identification of collagen remodelling in striae.

PMID- 29595225
TI  - Tobacco smoking and hidradenitis suppurativa: associated disease and an important
      modifiable risk factor.

PMID- 29595226
TI  - Light on fumaric acid esters therapy for psoriasis.

PMID- 29595227
TI  - Image Gallery: Dermatophytic pseudomycetoma caused by Microsporum canis.

PMID- 29595228
TI  - Autoinflammation behind the curtain.

PMID- 29595229
TI  - Cell delivery using microneedle devices: a new approach to treat depigmenting
      disorders.

PMID- 29595230
TI  - Corrigenda.

PMID- 29595231
TI  - Habit reversal therapy quickly and significantly contributes to the management of
      children with atopic eczema.

PMID- 29595232
TI  - Interleukin-36 cytokine family signalling in hidradenitis suppurativa.

PMID- 29595233
TI  - Is new better than tried and tested? Topical atopic dermatitis treatment in
      context.

PMID- 29595234
TI  - Image Gallery: A hard 'pebbly' plaque stuck on the upper eyelid.

PMID- 29595235
TI  - Spectrum of cutaneous manifestations among patients with GATA2 deficiency.

PMID- 29595236
TI  - The heterogeneous mutational landscape of pustular psoriasis.

PMID- 29595237
TI  - Editors Choice.

PMID- 29595238
TI  - Corrigenda.

PMID- 29595239
TI  - Ixekizumab and psoriasis: an important entry into the therapeutic landscape.

PMID- 29595240
TI  - Image Gallery: Symmetrical whirled eschars on the face in mycosis fungoides.

PMID- 29595241
TI  - Combining Inkjet Printing with Emulsion Solvent Evaporation to Pattern Polymeric
      Particles.
AB  - We demonstrate a concept to produce deposits of polymer in the form of particles
      by inkjet printing an emulsion in which the discrete phase evaporates
      preferentially. An oil/water emulsion with polymer contained inside the oil phase
      is used as ink for printing. Circular deposits of spherical polymer particles
      with uniform thickness are obtained. The effects of the hydrophobicity of
      substrates and the physical properties of the oil on the morphology of the
      deposits are explored. The deposit of aggregated polymeric particles can be
      transformed into a uniform film by annealing if required. This strategy for the
      patterning of polymer materials in the form of either particles or a film works
      for mixtures of polymers and functional cargoes.

PMID- 29595242
TI  - Compliance-Free Multileveled Resistive Switching in a Transparent 2D Perovskite
      for Neuromorphic Computing.
AB  - We demonstrate the pulsed voltage tunable multileveled resistive switching (RS)
      across a promising transparent energy material of (C4H9NH3)2PbBr4. The X-ray
      diffraction and scanning electron microscopy results confirm the growth of (001)
      plane-orientated nanostructures of (C4H9NH3)2PbBr4 with an average size of ~360
      nm. The device depicts optical transmittance higher than 70% in the visible
      region and efficient absorbance in the ultraviolet region. The current-voltage
      measurement shows the bipolar RS. In addition, depending on the magnitude of
      applied electric pulse, the current across the device can be flipped in four
      different levels, which remain stable for long time, indicating multimode RS.
      Further, the current across the device increases gradually by applying continuous
      pulses, similar to the biological synapses. The observed results are attributed
      to the electric field-induced ionic migration across the (C4H9NH3)2PbBr4. The
      existing study should open a new avenue to apply this promising energy material
      of perovskite for multifunctional advanced devices.

PMID- 29595243
TI  - Sol-Gel Synthesis and in Situ X-ray Diffraction Study of Li3Nd3W2O12 as a Lithium
      Container.
AB  - In this work, garnet-framework Li3Nd3W2O12 as a novel insertion-type anode
      material has been prepared via a facile sol-gel method and examined as a lithium
      container for lithium ion batteries (LIBs). Li3Nd3W2O12 shows a charge capacity
      of 225 mA h g-1 at 50 mA g-1, and with the current density increasing up to 500
      mA g-1, the charge capacity can still be maintained at 186 mA h g-1. After
      cycling at 500 mA g-1 for 500 cycles, Li3Nd3W2O12 retains about 85% of its first
      charge capacity changed from 190.2 to 161 mA h g-1. Furthermore, in situ X-ray
      diffraction technique is adopted for the understanding of the
      insertion/extraction mechanism of Li3Nd3W2O12. The full-cell configuration
      LiFePO4/Li3Nd3W2O12 is also assembled to evaluate the potential of Li3Nd3W2O12
      for practical application. These results show that Li3Nd3W2O12 is such a
      promising anode material for LIBs with excellent electrochemical performance and
      stable structure.

PMID- 29595244
TI  - Injectable Coacervate Hydrogel for Delivery of Anticancer Drug-Loaded
      Nanoparticles in vivo.
AB  - In this study, bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was
      encapsulated in micellar nanoparticles having a catechol-functionalized
      polycarbonate core through a pH-sensitive covalent bond between phenylboronic
      acid (PBA) in BTZ and catechol, and these drug-loaded micelles were incorporated
      into hydrogels to form micelle/hydrogel composites. A series of injectable,
      biodegradable hydrogels with readily tunable mechanical properties were formed
      and optimized for sustained delivery of the BTZ-loaded micelles through ionic
      coacervation between PBA-functionalized polycarbonate/poly(ethylene glycol) (PEG)
      "ABA" triblock copolymer and a cationic one having guanidinium- or thiouronium
      functionalized polycarbonate as "A" block. An in vitro release study showed the
      pH dependence in BTZ release. At pH 7.4, the BTZ release from the
      micelle/hydrogel composite remained low at 7%, whereas in an acidic environment,
      ~85% of BTZ was released gradually over 9 days. In vivo studies performed in a
      multiple myeloma MM.1S xenograft mouse model showed that the tumor progression of
      mice treated with BTZ-loaded micelle solution was similar to that of the control
      group, whereas those treated with the BTZ-loaded micelle/hydrogel composite
      resulted in significant delay in the tumor progression. The results demonstrate
      that this hydrogel has great potential for use in subcutaneous and sustained
      delivery of drug-loaded micelles with superior therapeutic efficacy.

PMID- 29595245
TI  - Stimuli-Responsive DNA Microcapsules for SERS Sensing of Trace MicroRNA.
AB  - In this work, one stimuli-responsive DNA microcapsule was designed to combine
      duplex-specific nuclease (DSN) amplification strategy and surface-enhanced Raman
      spectroscopy (SERS) technology for sensitive detection of microRNA 155 (miRNA
      155). First, toluidine blue (TB) as Raman dye and CaCO3 as core templates co
      precipitated to form TB@CaCO3 composite. Then, DNA networks were layer by layer
      constructed with oligonucleotide layers cross-linked by linker ssDNA L to lock
      TB@CaCO3 inside. In the presence of ethylenediaminetetraacetic acid, the core
      CaCO3 would be dissolved to form TB-loading DNA microcapsule. With target miRNA
      155-induced DSN signal amplification, a large amount of simulative target ssDNA D
      was obtained, which can completely complement with the linker L on the DNA
      networks, destroying the microcapsule to release TB and obtain a strong Raman
      signal. So by this smart design, a SERS platform was fabricated on the basis of
      the stimuli-responsive DNA microcapsule to detect miRNA 155 from 1 fM to 10 nM
      with a detection limit of 0.67 fM. In the present study, the programmable
      property and rapid response speed of DNA microcapsule, which helped in
      fabrication of a new potential biosensing technology for miRNA detection that is
      anticipated to be applied for clinical diagnosis.

PMID- 29595246
TI  - Reduction-Responsive Codelivery System Based on a Metal-Organic Framework for
      Eliciting Potent Cellular Immune Response.
AB  - Utilizing nanoparticles to deliver subunit vaccines can be viewed as a promising
      strategy for enhancing the immune response, especially with regard to cellular
      immunity to fight against infectious viruses and malignant cancer. Nevertheless,
      its applications are still far from practicality because of some limitations such
      as high cost, non-biocompatibility, non-biodegradability, and the inefficient
      stimulation of cytotoxic T lymphocyte (CTL) response. In this study, we use metal
      organic framework (MOF) MIL-101-Fe-NH2 nanoparticles as carriers to fabricate an
      innovative reduction-responsive antigen delivery system for cotransporting the
      antigen model ovalbumin (OVA) and an immune adjuvant, unmethylated cytosine
      phosphate-guanine (CpG) oligonucleotide. In vitro cellular tests show that the
      MOF nanoparticles can not only greatly improve the uptake of OVA by the antigen
      presenting cells but also smartly deliver both OVA and CpG into the same cell. By
      feat of the reductively controllable release of OVA and the promoting function of
      CpG, the delivery system can elicit strong cellular immunity and CTL response in
      mice. Moreover, the increased frequencies of effector memory T cells inspired by
      the delivery system indicate that it can induce a potent immune memory response.
      These results demonstrate that MOF nanoparticles are excellent vehicles for
      codelivering antigen and immune adjuvant and may find wider applications in
      biomedical fields.

PMID- 29595247
TI  - Visible Light Driven Bromide Oxidation and Ligand Substitution Photochemistry of
      a Ru Diimine Complex.
AB  - The complex [Ru(deeb)(bpz)2]2+ (RuBPZ2+, deeb = 4,4'-diethylester-2,2'
      bipyridine, bpz = 2,2'-bipyrazine) forms a single ion pair with bromide,
      [RuBPZ2+, Br-]+, with Keq = 8400 +/- 200 M-1 in acetone. The RuBPZ2+ displayed
      photoluminescence (PL) at room temperature with a lifetime of 1.75 MUs. The
      addition of bromide to a RuBPZ2+ acetone solution led to significant PL quenching
      and Stern-Volmer plots showed upward curvature. Time-resolved PL measurements
      identified two excited state quenching pathways, static and dynamic, which were
      operative toward [RuBPZ2+, Br-]+ and free RuBPZ2+, respectively. The single ion
      pair [RuBPZ2+, Br-]+* had a lifetime of 45 +/- 5 ns, consistent with an electron
      transfer rate constant, ket = (2.2 +/- 0.3) * 107 s-1. In contrast, RuBPZ2+* was
      dynamically quenched by bromide with a quenching rate constant, kq = (8.1 +/-
      0.1) * 1010 M-1 s-1. Nanosecond transient absorption revealed that both the
      static and dynamic pathways yielded RuBPZ+ and Br2*- products that underwent
      recombination to regenerate the ground state with a second-order rate constant,
      kcr = (2.3 +/- 0.5) * 1010 M-1 s-1. Kinetic analysis revealed that RuBPZ+ was a
      primary photoproduct, while Br2*- was secondary product formed by the reaction of
      a Br* with Br-, k = (1.1 +/- 0.2) * 1010 M-1 s-1. Marcus theory afforded an
      estimate of the formal reduction potential for E0(Br*/-) in acetone, 1.42 V vs
      NHE. A 1H NMR analysis indicated that the ion-paired bromide was preferentially
      situated close to the RuII center. Prolonged steady state photolysis of RuBPZ2+
      and bromide yielded two ligand-substituted photoproducts, cis- and trans
      Ru(deeb)(bpz)Br2. A photochemical intermediate, proposed to be
      [Ru(deeb)(bpz)(kappa1-bpz)(Br)]+, was found to absorb a second photon to yield
      cis- and trans-Ru(deeb)(bpz)Br2 photoproducts.

PMID- 29595248
TI  - In Situ Triaxial Testing To Determine Fracture Permeability and Aperture
      Distribution for CO2 Sequestration in Svalbard, Norway.
AB  - On Svalbard, Arctic Norway, an unconventional siliciclastic reservoir, relying on
      (micro)fractures for enhanced fluid flow in a low-permeable system, is
      investigated as a potential CO2 sequestration site. The fractures' properties at
      depth are, however, poorly understood. High resolution X-ray computed tomography
      (micro-CT) imaging allows one to visualize such geomaterials at reservoir
      conditions. We investigated reservoir samples from the De Geerdalen Formation on
      Svalbard to understand the influence of fracture closure on the reservoir fluid
      flow behavior. Small rock plugs were brought to reservoir conditions, while
      permeability was measured through them during micro-CT imaging. Local fracture
      apertures were quantified down to a few micrometers wide. The permeability
      measurements were complemented with fracture permeability simulations based on
      the obtained micro-CT images. The relationship between fracture permeability and
      the imposed confining pressure was determined and linked to the fracture
      apertures. The investigated fractures closed due to the increased confining
      pressure, with apertures reducing to approximately 40% of their original size as
      the confining pressure increased from 1 to 10 MPa. This coincides with a
      permeability drop of more than 90%. Despite their closure, fluid flow is still
      controlled by the fractures at pressure conditions similar to those at the
      proposed storage depth of 800-1000 m.

PMID- 29595249
TI  - Criticality in the Brain: Evidence and Implications for Neuromorphic Computing.
AB  - We have discovered an unexpected correlation between the operational temperature
      of the brain and cognitive abilities across a wide variety of animal species.
      This correlation is extracted from available data in the literature of the
      temperature range Delta T at which an animal's brain can operate and its
      encephalization quotient EQ, which can be used as a proxy for cognitive ability.
      In particular, we found a power-law dependence between Delta T and EQ. These data
      support the theory that the brain behaves as a critical system where temperature
      is one of the critical parameters, tuning the performance of the neural network.

PMID- 29595250
TI  - Carrier Mobility-Dominated Gas Sensing: A Room-Temperature Gas-Sensing Mode for
      SnO2 Nanorod Array Sensors.
AB  - Adsorption-induced change of carrier density is presently dominating inorganic
      semiconductor gas sensing, which is usually operated at a high temperature.
      Besides carrier density, other carrier characteristics might also play a critical
      role in gas sensing. Here, we show that carrier mobility can be an efficient
      parameter to dominate gas sensing, by which room-temperature gas sensing of
      inorganic semiconductors is realized via a carrier mobility-dominated gas-sensing
      (CMDGS) mode. To demonstrate CMDGS, we design and prepare a gas sensor based on a
      regular array of SnO2 nanorods on a bottom film. It is found that the key for
      determining the gas-sensing mode is adjusting the length of the arrayed nanorods.
      With the change in the nanorod length from 340 to 40 nm, the gas-sensing behavior
      changes from the conventional carrier-density mode to a complete carrier-mobility
      mode. Moreover, compared to the carrier density-dominating gas sensing, the
      proposed CMDGS mode enhances the sensor sensitivity. CMDGS proves to be an
      emerging gas-sensing mode for designing inorganic semiconductor gas sensors with
      high performances at room temperature.

PMID- 29595251
TI  - Force Spectroscopy on a Cell Drum: AFM Measurements on the Basolateral Side of
      Cells via Inverted Cell Cultures.
AB  - The elasticity of a cell is one of the most critical measures of the difference
      between cancerous cells and healthy cells: cancer cells tend to be softer than
      healthy cells, and highly invasive cells tend to be more elastic than less
      aggressive cells. In this work, we present the novel "bottom-up" cell force
      spectroscopy method for the biophysical characterization of cancer cells, in
      which an atomic force microscopy (AFM) tip approach from the backside of a net
      shaped culture substrate exposing the basolateral cell membrane drum, and compare
      it with the conventional "top-down" AFM measurements. We used two different human
      pancreatic carcinoma cell lines, PaTu8988S and PaTu8988T. Our bottom-up AFM tip
      approach provided a more statistically synchronized distribution of the measured
      elastic moduli of the cells, demonstrating its superior applicability for the
      clinical use of force spectroscopy, which is not attainable with the conventional
      top-down AFM approach.

PMID- 29595252
TI  - Detection of Pathogenic Microorganisms by Microfluidics Based Analytical Methods.
AB  - Microfluidics based biochemical analysis shows distinctive advantages for fast
      detection of pathogenic microorganisms. This Feature summarizes the progress in
      the past decade on microfluidic methods for purification and detection of
      pathogenic bacteria and viruses as well as their applications in food safety
      control, environmental monitoring, and clinical diagnosis.

PMID- 29595253
TI  - Magnetic Nanozyme-Linked Immunosorbent Assay for Ultrasensitive Influenza A Virus
      Detection.
AB  - Rapid and sensitive detection of influenza virus is of soaring importance to
      prevent further spread of infections and adequate clinical treatment. Herein, an
      ultrasensitive colorimetric assay called magnetic nano(e)zyme-linked
      immunosorbent assay (MagLISA) is suggested, in which silica-shelled magnetic
      nanobeads (MagNBs) and gold nanoparticles are combined to monitor influenza A
      virus up to femtogram per milliliter concentration. Two essential strategies for
      ultrasensitive sensing are designed, i.e., facile target separation by MagNBs and
      signal amplification by the enzymelike activity of gold nanozymes (AuNZs). The
      enzymelike activity was experimentally and computationally evaluated, where the
      catalyticity of AuNZ was tremendously stronger than that of normal biological
      enzymes. In the spiked test, a straightforward linearity was presented in the
      range of 5.0 * 10-15-5.0 * 10-6g.mL-1 in detecting the influenza virus A (New
      Caledonia/20/1999) (H1N1). The detection limit is up to 5.0 * 10-12 g.mL-1 only
      by human eyes, as well as up to 44.2 * 10-15 g.mL-1 by a microplate reader, which
      is the lowest record to monitor influenza virus using enzyme-linked immunosorbent
      assay-based technology as far as we know. Clinically isolated human serum samples
      were successfully observed at the detection limit of 2.6 PFU.mL-1. This novel
      MagLISA demonstrates, therefore, a robust sensing platform possessing the
      advances of fathomable sample separation, enrichment, ultrasensitive readout, and
      anti-interference ability may reduce the spread of influenza virus and provide
      immediate clinical treatment.

PMID- 29595254
TI  - From Static to Dynamic: Electron Density of HOMO at Biaryl Linkage Controls the
      Mechanism of Hole Delocalization.
AB  - In order to extend the physical length of hole delocalization in a molecular
      wire, chromophores of increasing size are often desired. However, the effect of
      size on the efficacy and mechanism of hole delocalization remains elusive. Here,
      we employ a model set of biaryls to show that with increasing chromophore size,
      the mechanism of steady-state hole distribution switches from static
      delocalization in biaryls with smaller chromophores to dynamic hopping, as
      exemplified in the largest system, tBuHBC2 (i.e., "superbiphenyl"), which
      displays a vanishingly small electronic coupling. This important finding is
      analyzed with the aid of Huckel molecular orbital and Marcus-Hush theories. Our
      findings will enable the rational design of the novel molecular wires with length
      invariant redox/optical properties suitable for long-range charge transfer.

PMID- 29595255
TI  - Linking Thermodynamics to Pollutant Reduction Kinetics by Fe2+ Bound to Iron
      Oxides.
AB  - Numerous studies have reported that pollutant reduction rates by ferrous iron
      (Fe2+) are substantially enhanced in the presence of an iron (oxyhydr)oxide
      mineral. Developing a thermodynamic framework to explain this phenomenon has been
      historically difficult due to challenges in quantifying reduction potential ( EH)
      values for oxide-bound Fe2+ species. Recently, our group demonstrated that EH
      values for hematite- and goethite-bound Fe2+ can be accurately calculated using
      Gibbs free energy of formation values. Here, we tested if calculated EH values
      for oxide-bound Fe2+ could be used to develop a free energy relationship capable
      of describing variations in reduction rate constants of substituted
      nitrobenzenes, a class of model pollutants that contain reducible aromatic nitro
      groups, using data collected here and compiled from the literature. All the data
      could be described by a single linear relationship between the logarithms of the
      surface-area-normalized rate constant ( kSA) values and EH and pH values [log(
      kSA) = - EH/0.059 V - pH + 3.42]. This framework provides mechanistic insights
      into how the thermodynamic favorability of electron transfer from oxide-bound
      Fe2+ relates to redox reaction kinetics.

PMID- 29595257
TI  - Azoreductase and Target Simultaneously Activated Fluorescent Monitoring for
      Cytochrome c Release under Hypoxia.
AB  - Hypoxia-induced cell apoptosis is closely related to degenerative diseases,
      autoimmune disorders, and tumor disease. In the process of apoptosis, the release
      of cytochrome c (Cyt c) is deemed to be a critical factor of the intrinsic
      pathway. Strategies for tracking Cyt c release in living cells based on the
      subcellular localization have been proposed recently. However, they are
      inherently lack of specificity for distinguishing the release of Cyt c in
      apoptotic process induced by hypoxia from other stimulus. In this paper, an
      azoreductase and target simultaneously activated fluorescent aptameric nanosensor
      integrating gold nanoparticles (AuNPs) and Cyt c-targeted aptamer-consisted
      double-stranded DNA hybridization complex (DSDHC) was proposed. It is worth
      noting that the employment of azobenzene moiety labeled on the DSDHC first
      ensured the aptameric nanosensor could be conjugated to the surface of AuNPs and
      then specifically reduced by hypoxia-related azoreductase. Upon Cyt c released
      from mitochondrion under hypoxia, the competitive displacement of Cyt c
      subsequently activated the fluorescence of the aptameric nanosensor and the
      fluorescence enhancement depended principally on the content of Cyt c release.
      Inspired by this, a new strategy for quantitative analysis and in situ imaging of
      Cyt c under hypoxic condition was proposed. The high spatial resolution
      monitoring of the dynamics of Cyt c release under hypoxia will offer a
      potentially rich opportunity to understand the apoptotic mechanism under hypoxic
      conditions, thus further facilitating risk assessment and risk reduction for
      hypoxic environments.

PMID- 29595256
TI  - Effects of Dietary l-Arginine and N-Carbamylglutamate Supplementation on
      Intestinal Integrity, Immune Function, and Oxidative Status in Intrauterine
      Growth-Retarded Suckling Lambs.
AB  - This study investigated the effects of dietary l-arginine (Arg) and N
      carbamylglutamate (NCG) supplementation on intestinal integrity, immune function,
      and oxidative status in intrauterine-growth-retarded (IUGR) suckling lambs. A
      total of 48 newborn Hu lambs of normal birth weight (CON) and IUGR were allocated
      randomly into four groups of 12 animals each: CON, IUGR, IUGR + 1% Arg, or IUGR +
      0.1% NCG. All lambs were raised for a period of 21 days from 7 to 28 days after
      birth. The Arg or NCG group exhibited improved ( p < 0.05) final body weights
      compared to that of the IUGR group. In comparison to the IUGR lambs, the
      apoptotic percentage was lower ( p < 0.05) in the ileum of IUGR lambs
      supplemented with Arg and NCG. In addition, in comparison to IUGR, the
      concentrations of protein carbonyl and malondialdehyde were lower ( p < 0.05) and
      the reduced glutathione (GSH) concentration and ratio of GSH/oxidized glutathione
      were greater ( p < 0.05) in the jejunum, duodenum, and ileum of IUGR + 1% Arg or
      0.1% NCG lambs. In comparison to the IUGR group, the mRNA abundance of myeloid
      differentiation factor 88, toll-like receptor 9, toll-like receptor 4,
      interleukin 6, and fuclear factor-kappaB was lower ( p < 0.05) and the mRNA
      abundance of superoxide dismutase 1, B-cell lymphoma/leukaemia 2, zonula
      occludens-1 (ZO-1), and occludin was greater in the ileum of the IUGR lambs
      supplemented with Arg or NCG. Furthermore, the protein abundance of ZO-1 and
      claudin-1 in the ileum was greater ( p < 0.05) in the IUGR + 1% Arg or 0.1% NCG
      lambs. The results show that Arg or NCG supplementation improves the growth,
      intestinal integrity, immune function, and oxidative status in IUGR Hu suckling
      lambs.

PMID- 29595258
TI  - Reductive O2 Binding at a Dihydride Complex Leading to Redox Interconvertible MU
      1,2-Peroxo and MU-1,2-Superoxo Dinickel(II) Intermediates.
AB  - Dioxygen activation at nickel complexes is much less studied than for the
      biologically more relevant iron or copper systems but promises new reactivity
      patterns because of the distinct coordination chemistry of nickel. Here we report
      that a pyrazolate-based dinickel(II) dihydride complex [KL(Ni-H)2] (1a) smoothly
      reacts with O2 via reductive H2 elimination to give the MU-1,2-peroxo
      dinickel(II) complex [KLNi2(O2)] (2a) and, after treatment with dibenzo[18]-crown
      6, the separated ion pair [K(DB18C6)][LNi2(O2)] (2b); these are the first MU-1,2
      peroxo dinickel intermediates to be characterized by X-ray diffraction. In 2a,
      the K+ is found side-on associated with the peroxo unit, revealing a pronounced
      weaking of the O-O bond: d(O-O) = 1.482(2) A in 2a versus 1.465(2) in 2b; nu(O-O)
      = 720 cm-1 in 2a versus 755 cm-1 in 2b. Reaction of 1a (or 2a/2b) with an excess
      of O2 cleanly leads to [LNi2(O2)] (3), which was shown by X-ray crystallography (
      d(O-O) = 1.326(2) A), electron paramagnetic resonance and Raman spectroscopy
      (nu(O-O) = 1007 cm-1), magnetic measurements, and density functional theory
      calculations to feature two low-spin d8 nickel(II) ions and a genuine MU-1,2
      superoxo ligand with the unpaired electron in the out-of-plane pi*O-O orbital.
      These MU-1,2-superoxo and MU-1,2-peroxo species, all containing the O2-derived
      unit within the cleft of the dinickel(II) core, can be reversibly interconverted
      chemically and also electrochemically at very low potential ( E1/2 = -1.22 V vs
      Fc/Fc+). Initial reactivity studies indicate that protonation of 2a, or reaction
      of 3 with TEMPO-H, ultimately gives the MU-hydroxo dinickel(II) complex [LNi2(MU
      OH)] (4). This work provides an entire new series of closely related and
      unusually rugged Ni2/O2 intermediates, avoiding the use of unstable nickel(I)
      precursors but storing the redox equivalents for reductive O2-binding in
      nickel(II) hydride bonds.

PMID- 29595259
TI  - Conformationally Induced Off-On Cell Membrane Chemosensor Targeting Receptor
      Protein-Tyrosine Kinases for in Vivo and in Vitro Fluorescence Imaging of
      Cancers.
AB  - Molecules capable of monitoring receptor protein-tyrosine kinase expression could
      potentially serve as useful tools for cancer diagnosis due to the overexpression
      of tyrosine kinases during tumor growth and metastasis. In this work, a
      conformationally induced "off-on" tyrosine kinase cell membrane fluorescent
      sensor (SP1) was designed and evaluated for the detection and imaging of receptor
      protein-tyrosine kinases in vivo and in vitro. SP1 consists of sunitinib and
      pyrene linked via hexamethylenediamine and displays quenched fluorescence as a
      dimer. The fluorescence of SP1 is restored in the presence of receptor protein
      tyrosine kinases upon strong interaction with SP1 at the target terminal. The
      unique signal response mechanism enables SP1 use for fluorescence microscopy
      imaging of receptor protein-tyrosine kinases in the cell membranes of living
      cells, allowing for the rapid differentiation of cancer cells from normal cells.
      SP1 can be used to visualize the chick embryo chorioallantoic membrane and mouse
      model tumors, suggesting its possible application for early cancer diagnosis.

PMID- 29595260
TI  - Palladium-Catalyzed Domino Reaction for Stereoselective Synthesis of
      Multisubstituted Olefins: Construction of Blue Luminogens.
AB  - The first Pd-catalyzed multicomponent reaction of aryl iodides, alkenyl bromides,
      and strained alkenes has been developed, which allowed us to synthesize a variety
      of multisubsituted olefins in yields of 45-96% with excellent stereoselectivity.
      The configuration of the product was controlled by the configuration of the
      alkenyl bromides. Moreover, this practical methodology employing readily
      available substrates was found to be tolerant to a wide range of functional
      groups. Fifty six examples of highly stereoselective tri- or tetrasubstituted
      olefins have been successfully synthesized via this methodology. Most of the
      synthesized tetrasubstituted olefins are good aggregation-induced emission (AIE)
      luminogens.

PMID- 29595262
TI  - Serine-Lysine Peptides as Mediators for the Production of Titanium Dioxide:
      Investigating the Effects of Primary and Secondary Structures Using Solid-State
      NMR Spectroscopy and DFT Calculations.
AB  - A biomimetic approach to the formation of titania (TiO2) nanostructures is
      desirable because of the mild conditions required in this form of production. We
      have identified a series of serine-lysine peptides as candidates for the
      biomimetic production of TiO2 nanostructures. We have assayed these peptides for
      TiO2-precipitating activity upon exposure to titanium bis(ammonium
      lactato)dihydroxide and have characterized the resulting coprecipitates using
      scanning electron microscopy. A subset of these assayed peptides efficiently
      facilitates the production of TiO2 nanospheres. Here, we investigate the process
      of TiO2 nanosphere formation mediated by the S-K peptides KSSKK- and SKSK3SKS
      using one-dimensional and two-dimensional solid-state NMR (ssNMR) on peptide
      samples with uniformly 13C-enriched residues. ssNMR is used to assign 13C
      chemical shifts (CSs) site-specifically in each free peptide and TiO2-embedded
      peptide, which are used to derive secondary structures in the neat and TiO2
      coprecipitated states. The backbone 13C CSs are used to assess secondary
      structural changes undergone during the coprecipitation process. Side-chain 13C
      CS changes are analyzed with density functional theory calculations and used to
      determine side-chain conformational changes that occur upon coprecipitation with
      TiO2 and to determine surface orientation of lysine side chains in TiO2-peptide
      composites.

PMID- 29595263
TI  - Synthesis and Spectroscopic Properties of Fluorinated Coumarin Lysine
      Derivatives.
AB  - The site-selective incorporation of fluorescent amino acids into proteins has
      emerged as a valuable alternative to expressible protein reporters. For
      successful application, a robust and scalable, yet flexible, route to non-natural
      amino acids is required. This work describes an improved synthesis of coumarin
      conjugated lysine derivatives where fluorinated variants are accessed. These
      analogues can be utilized at low pH and should find application probing
      biological processes that operate under acidic conditions.

PMID- 29595264
TI  - Synthesis and Characterization of Ferrocene Based Hemicages.
AB  - We present a series of tripodal ligands L1-3, which fold into hemicages C1-3 by
      using coordination-driven dynamic combinational chemistry. The identities of
      these hemicages were characterized using 1H NMR, 1H-1H COSY, DOSY, and ESI-TWIM
      MS. Free rotation of the ferrocene structural units in the ligands affords an
      adaptable directionality, which is essential for the construction of these
      hemicages. Encapsulation of adamantane by C2 indicates the presence of a well
      defined inner cavity as the binding pocket.

PMID- 29595265
TI  - Conformational Properties of Aromatic Oligoamides Bearing Pyrrole Rings.
AB  - N-Alkylbenzanilides generally exist in cis conformation both in the crystalline
      state and in various solvents, and this cis conformational preference can be
      utilized to construct dynamic helical oligoamides. Here, we synthesized the
      pyrrole-containing amides 2-5 and their oligomers 6-8 and examined their
      conformations in the crystalline state and in solution. All the N-methylated
      amides showed cis conformational preference in solution, but the ratio of the cis
      isomer was decreased when the amide bond was attached at the 4-position of the
      pyrrole ring, probably because the destabilization of the trans conformer due to
      electronic repulsion between the pyrrole pi electrons and the amide carbonyl lone
      pair electrons is reduced due to the small torsion angle between the 5-membered N
      pyrrole and the amide bond. In the crystalline state, N-methylated amides showed
      cis structure, except for compound 5, and cis conformational preference was
      observed for the pyrrole amides. The CD spectra of oligoamides 15-18 bearing
      chiral N-substituents were consistent with the presence of dynamic and well
      defined chiral foldamers, which were structurally distinct from N-alkylated poly(
      p-benzamide)s 1.

PMID- 29595266
TI  - Mechanoresponsive Tuning of Anisotropic Wetting on Hierarchically Structured
      Patterns.
AB  - Here, we propose a simple mechanoresponsive system on patterned soft surfaces to
      manipulate both anisotropy and orientation of liquid wetting. On the
      poly(dimethylsiloxane) embedding line patterned structures, additional
      topographies, such as wrinkles and cracks, can be provided by applying
      compressive and tensile stress, respectively. This tunable hierarchy of
      structures with the different scales and directions of lines, wrinkles, and
      cracks allow the mechanoresponsive control of anisotropic wetting in a single
      platform. In addition, the wetting behavior on those surfaces is precisely
      investigated based on the concept of critical contact angle to overcome the
      ridges in a step flow.

PMID- 29595267
TI  - Tetrahydroquinoline Ring as a Versatile Bioisostere of Tetralin for Melatonin
      Receptor Ligands.
AB  - A new family of melatonin receptor ligands, characterized by a
      tetrahydroquinoline (THQ) scaffold carrying an amide chain in position 3, was
      devised as conformationally constrained analogs of flexible N-anilinoethylamides
      previously developed. Molecular superposition models allowed to identify the
      patterns of substitution conferring high receptor binding affinity and to support
      the THQ ring as a suitable scaffold for the preparation of melatonin ligands. The
      biological activity of 3-acylamino-THQs was compared with that of the
      corresponding tetralin derivatives. The THQ ring proved to be a versatile
      scaffold for easy feasible MT1 and MT2 ligands, which resulted as more polar
      bioisosteres of their tetralin analogs. Potent partial agonists, with
      subnanomolar binding affinity for the MT2 receptor, were obtained, and a new
      series of THQ derivatives is presented. The putative binding mode of potent THQs
      and tetralines was discussed on the basis of their conformational equilibria as
      inferred from molecular dynamics simulations and experimental NMR data.

PMID- 29595268
TI  - Halide Composition Controls Electron-Hole Recombination in Cesium-Lead Halide
      Perovskite Quantum Dots: A Time Domain Ab Initio Study.
AB  - We demonstrate that halide content strongly affects nonradiative electron-hole
      recombination in all-inorganic perovskite quantum dots (QDs). Using time domain
      density functional theory and nonadiabatic molecular dynamics, we show that
      replacing half of the bromines with iodines in a CsPbBr3 QD extends the charge
      carrier lifetime by a factor of 5, while complete replacement extends the
      lifetime by a factor of 8. Doping with iodines decreases the nonadiabatic charge
      phonon coupling because iodines are heavier and slower than bromines and because
      the overlap between the electron and hole wave functions is reduced. In general,
      the nonradiative electron-hole recombination proceeds slowly, on a nanosecond
      time scale, due to small sub-1 meV nonadiabatic coupling and short sub-10 fs
      coherence times. The obtained recombination times and their dependence on the
      halogen content show excellent agreement with experiments. Our study suggests
      that the power conversion efficiencies of solar cells can be controlled by
      changing the halide composition in all-inorganic perovskite QDs.

PMID- 29595269
TI  - Synthesis and Characterization of Isodiphenylfluorindone and
      Isodiphenylfluorindinone.
AB  - Isodiphenylfluorindone 6 and isodiphenylfluorindinone 7 are synthesized. The
      former reacts with NaOMe to give the 13-methoxyisodiphenylfluorindone 22 (95%),
      while the latter reacts with 70% perchloric acid to give the bisperchlorate 21
      (87%) and with MnO2 dimerizes to give 13,13'-bi(isodiphenylfluorindone) 4 (60%).
      UV-vis, NMR, CV, and DFT computational studies support the structural assignments
      of all products. Single-crystal X-ray diffraction studies are reported for
      isodiphenylfluorindinone 7.

PMID- 29595271
TI  - Synthesis and Evaluation of O2-Derived Diazeniumdiolates Activatable via
      Bioorthogonal Chemistry Reactions in Living Cells.
AB  - A class of O2-alkyl derived diazeniumdiolates 3a-f and 4a-c were designed and
      synthesized as new bioorthogonal NO precursors, which can be effectively uncaged
      in the presence of a palladium catalyst via bioorthogonal bond cleavage reactions
      to generate NO in living cancer cells, eliciting potent antiproliferative
      activity.

PMID- 29595270
TI  - Metal-Dielectric Parabolic Antenna for Directing Single Photons.
AB  - Quantum emitters radiate light omni-directionally, making it hard to collect and
      use the generated photons. Here, we propose a three-dimensional metal-dielectric
      parabolic antenna surrounding an individual quantum dot as a source of collimated
      single photons, which can then be easily extracted and manipulated. Our
      fabrication method relies on a single optically induced polymerization step once
      the selected emitter has been localized by confocal microscopy. Compared to
      conventional nanoantennas, our geometry does not require near-field coupling, and
      it is, therefore, very robust against misalignment issues and minimally affected
      by absorption in the metal. The parabolic antenna provides one of the largest
      reported experimental directivities ( D = 106) and the lowest beam divergences
      (Theta1/2 = 13.5 degrees ) and a broadband operation over all of the visible and
      near-infrared range together with extraction efficiency of more than 96%,
      offering a practical advantage for quantum technological applications.

PMID- 29595272
TI  - Stereochemical Study of Puna'auic Acid, an Allenic Fatty Acid from the Eastern
      Indo-Pacific Cyanobacterium Pseudanabaena sp.
AB  - The isolation and structure elucidation of puna'auic acid, an allenic fatty acid
      isolated from a marine cyanobacterium, is described. All configurations were
      first assessed through molecular modeling of NMR and ECD spectra and then
      confirmed through a straightforward enantioselective total synthesis of puna'auic
      acid featuring a key reductive opening of a propargylic epoxide.

PMID- 29595273
TI  - [Life threatening manifestations of lupus and antiphospholipid syndrome in
      internal medicine].
AB  - The clinical picture of systemic lupus and antiphospholipid syndrome is
      remarkably varied and disease manifestations are commonly very heterogeneous.
      Relatively often both diseases are associated with severe, acute and life
      threatening manifestations, which places demands on the knowledge of differential
      diagnostics and experience of the physicians. This article deals with the serious
      and mostly acute impairment of cardiovascular, respiratory, renal,
      gastrointestinal, hematopoietic or nervous systems, briefly discusses the acute
      pregnancy complication and summarizes the basic therapeutic option. It emphasizes
      the role of both, sometimes inseparable, diseases in differential diagnosis of
      acute symptoms in internal medicine.Key words: clinical symptoms - diagnostics -
      live threatening manifestations - lupus erythematosus - systemic antiphospholipid
      syndrome - therapy.

PMID- 29595274
TI  - [Chronic pain therapy in inflammatory rheumatic diseases].
AB  - Chronic pain is a common health problem related to most of inflammatory rheumatic
      disorders. It is pain that has persisted for at least 3 month and cannot be fully
      relieved by standard pain medication. 40-60 % of patients do not have adequate
      relief of their pain. Paramount in the management of chronic pain patients is
      assessment of the pain and its impact on physical and psychosocial functioning.
      Multidisciplinary and multimodal approach is of vital importance. Non-steroidal
      anti-rheumatic drugs (NSA) have been used mainly due to their strong analgesic
      effect, especially in the treatment of acute pain as well as their anti
      inflammatory effect in the treatment of chronic i pain. Long-term systemic
      administration of NSA may be associated with a number of serious side effects,
      which significantly limit NSA use in long term therapy. Due to opiophobia,
      opioids are insufficiently used treatment modality. Knowledge about pain and its
      management, as well as an awareness of barriers to effective pain therapy, are
      important not only for pain specialists but also primary care physicians.Key
      words: chronic pain - non-steroidal antirheumatic drugs - opiophobia - opioids -
      pain assessment - paracetamol - rheumatoid arthritis.

PMID- 29595275
TI  - [Rheumatoid arthritis].
AB  - Rheumatoid arthritis is an autoimmune disease manifested by a persistent
      inflammation of synovial joints, bone destruction, loss of cartilage and
      increased risk of cardiovascular and other intercurrent diseases. The treatment
      of rheumatoid arthritis should be based on the strategy of treat to target
      therapy which is achieving remission, in some cases low activity of the disease.
      Essential to the treat to target therapy are more frequent checkups and
      optimization of treatment based on disease activity. Methotrexate continues to be
      the essential medicine from the group of disease modifying antirheumatic drugs
      for rheumatoid arthritis treatment. At the start are frequently added
      glucocorticoids. If the effect is insufficient, biological therapy or use of
      targeted synthetic drugs can be considered. In this overview, the author will
      focus on epidemiology and risk factors, pathophysiology and in particular on the
      diagnostics, evaluation of activity and treatment of rheumatoid arthritis.Key
      words: diagnostics - disease activity - rheumatoid arthritis - treatment.

PMID- 29595276
TI  - [Axial spondyloarthritis].
AB  - Axial spondyloarthritis (axSpA) is a common name for the non-radiographic form of
      the disease and radiographic axial spondyloarthritis, known as ankylosing
      spondylitis (AS). The disease is typically manifested at a young age,
      characterized by affection of axial skeleton, and in the most severe form can
      lead to complete ankylosis of the spine. Etiology of diseases have not yet been
      clarified, however, the genetic background, especially the binding to HLA-B27
      antigen, is obvious. Clinical manifestations are dominated by chronic pain in the
      lower pain or buttocks that occurred in young age, in a large proportion of
      patients having the character of so-called inflammatory pain. In addition to the
      axial skeleton, axSpA there is also common affection of peripheral skeleton in
      the form of enthesitis, arthritis, and less often dactylitis. At present,
      enthesitis is considered as a hallmark of the entire spondyloarthritis group.
      Typical for axSpA is the frequent presence of extraskeletal manifestations in the
      form of uveitis, idiopathic intestinal inflammation and psoriasis. In the axSpA
      diagnosis, significant advances have been made in recent years in the field of
      imaging techniques. Magnetic resonance imaging can also identify the early stage
      of the disease before the development of structural lesions. Also, the newer
      concepts of the entire spondyloarthritis group, based on the 2009 ASAS
      (Assessment of SpondyloArthritis international Society) classification criteria,
      contributed to early diagnosis of the disease, and in particular to the
      underlying importance of association with HLA-B27 antigen and the presence of
      peripheral and non-articular manifestations. Non-steroidal anti-rheumatic drugs
      (NSAIDs) and TNFalpha blockers are effective axSpA therapy, which has been
      recently enhanced by interleukin 17 blockade (IL17).Key words: axial
      spondyloarthritis - biological treatment - enthesitis - extraarticular
      manifestations - magnetic resonance imaging - non-radiographic axial
      spondyloarthritis - sacroiliitis.

PMID- 29595277
TI  - [The role of magnetic resonance imaging in diagnostics of axial
      spondyloarthritis].
AB  - Axial spondyloarthritis (SpA) is a chronic inflammatory rheumatic disorder that
      primary affects axial skeleton. It comprises wide spectrum of patients with
      immune mediated spine inflammation, from early, so called non-radiographic axial
      spondyloarthritis to clinically evident ankylosing spondylitis. Conventional
      radiography is still the cornerstone of diagnosis, evaluation and classification
      of SpA. However, it has limitations in early disease, because it can only depict
      the consequences of inflammation for its inability to visualize soft tissue
      abnormalities within bone marrow. Magnetic resonance imaging (MRI) is superior to
      conventional radiography in early disease through its ability to visualize active
      inflammatory changes in sacroiliac joints when the pelvic radiographs are normal
      or equivocal. MRI of sacroiliac joints is also included to the Assessment of
      Axial Spondyloarthritis (ASAS) classification criteria for axial SpA. For
      classification purposes positive definition of MRI sacroiliitis was proposed with
      the clear presence of subchondral bone marrow edema (osteitis), which does not
      cross anatomical borders and is usually present on more consecutive slides. The
      more intense the signal is on fluid sensitive MRI sequences; more likely it
      reflects active inflammation, because small focal bone marrow edema lesions may
      occur in patients with mechanical back pain. It may be associated with signs of
      structural damage such as erosions, which can enhance diagnostic utility of MRI
      in cases of not highly suggestive appearance of osteitis. Contrast-enhanced
      imaging is not useful for routine diagnostic evaluation. When MRI findings are
      not clear, an additional MRI of the spine can be performed, especially of the
      area with the most pronounced complaints. Evidence of bone marrow edema in three
      or more vertebral edges is considered as highly suggestive of axial SpA,
      especially in patients of younger age, when degenerative changes are expected to
      play minor role for differential diagnosis.Key words: ankylosing spondylitis -
      axial spondyloarthritis - magnetic resonance imaging (MRI) - sacroiliitis.

PMID- 29595278
TI  - [Biological treatment of psoriatic arthritis].
AB  - Psoriatic arthritis (PsA) is a heterogeneous disease affecting, besides synovial
      joints, also the entheses, the soft tissues of the whole finger (dactylitis) and
      the axial skeleton. Currently the classification criteria CASPAR are used to
      diagnose PsA. In a large number of patients the disease leads to irreversible
      joint damage (X-ray, respectively clinical) which significantly reduces life
      quality and limits the patient in his/her everyday activities and also
      considerably limits their work capacity. There is evidence showing that early
      commencement of treatment and treat to target principle can significantly reduce
      this negative development. In recent time the knowledge of the disease
      pathogenesis has been extending and at the same time new drugs appear that act on
      the critical pathogenetic processes in a targeted way. These are biological drugs
      from the group of TNFalpha inhibitors and, most recently, also inhibitors of Th17
      - IL17 pathway. Together with that is further specified the treatment strategy
      and the way of its monitoring. These new findings have led to the update of
      recommendations for the treatment and monitoring of psoriatic arthritis by the
      Czech Society for Rheumatology.Key words: biological drugs - conventional
      synthetic disease-modifying antirheumatic drugs - early treatment - psoriatic
      arthritis - targeted synthetic disease modifying drugs - treat to target.

PMID- 29595279
TI  - [Systemic sclerosis in 2017].
AB  - Systemic sclerosis is classed as a diffuse (systemic) disease of connective
      tissue. It is a heterogeneous disease significantly shortening life expectancy.
      Its etiology is unknown. Pathogenetic interplay is assumed to involve a triad of
      pathological autoimmune inflammation, vasculopathy and fibrosis. Clinical
      manifestations can be classed based on the preponderant pathogenetic process.
      Vasculopathy is manifested by secondary Raynauds phenomenon with abnormal
      findings on the nailfold capillaroscopy, skin telangiectasias, gastric antral
      vascular ectasia, life threatening scleroderma renal crisis, digital ulcerations
      and prognostically severe pulmonary arterial hypertension. The treatment of
      vascular manifestations uses medicines with vasodilation effect. The
      manifestation of inflammation is accentuated by pleurisy, pericarditis, myositis,
      synovitis/arthritis and alveolitis. Finally, the manifestation of fibrosis
      predominates in association with dermatosclerosis, interstitial lung disease and
      fibrotic impairment of the gastrointestinal tract. Medicines with
      immunomodulatory or immunosupressive effects are used to affect the inflammation
      and fibrosis. Despite the aforementioned, there is still no universally effective
      treatment available. The pharmacological therapy of this disease is organ
      specific and symptomatic.Key words: capillaroscopy - digital ulcers -
      interstitial lung disease - pulmonary arterial hypertension - scleroderma renal
      crisis - systemic sclerosis.

PMID- 29595280
TI  - [Idiopathic inflammatory myopathies].
AB  - Idiopathic inflammatory myopathies form a heterogeneous group of acquired
      inflammatory diseases afflicting striated muscles. The disease is frequently
      accompanied by systemic and organ involvement. Dermatomyositis, polymyositis,
      cancer associated myositis, immune mediated necrotizing myopathy, myositis in
      overlap syndromes, juvenile myositis and inclusion body myositis are the most
      frequently encountered subtypes. The basic manifestation is usually painless
      muscle weakness brought about by inflammation and by other immune changes at the
      impacted muscles. Enzymes of muscle origin and myoglobin are found elevated in
      the circulation. There are changes in electrical properties of muscle fibers
      detected by EMG. A majority of patients have autoantibodies against nuclear or
      cytoplasmic antigens in their serum. They are often very specific for these
      diseases and frequently found in association with particular clinical
      presentations. For some patients with dermatomyositis the increased incidence of
      cancer is significantly associated with anti-TIF1gamma and anti-NXP2
      autoantibodies. Differential diagnostics of inflammatory myopathies is often
      difficult. Misdiagnosis for a non-inflammatory myopathy is not rare and therefore
      a very thorough diagnostic approach is necessary. Therapy aims to suppression of
      autoimmune response using glucocorticoids and immunosuppressive drugs. In large
      part of patients the response to standard treatment is not sufficient and less
      common synthetic compounds, biological drugs or intravenous immunoglobulins need
      to be used. Most patients with inclusion body myositis has limited or no effect
      of any treatment.Key words: autoantibodies - autoimmunity - inflammation -
      myopathy - myositis - systemic disease.

PMID- 29595281
TI  - [Novel trends in monitoring and therapy of ANCA associated vasculitides].
AB  - Vasculitides with positivity of autoantibodies to neutrophil leukocytes cytoplasm
      (ANCA, AAV) belong to primary vasculitides involving small and less commonly
      medium size blood vessels. Three different clinical types of AAV can be
      distinguished: granulomatosis with polyangiitis, eosinophilic granulomatosis with
      polyangiitis and microscopic polyangiitis. Since these autoantibodies seem to be
      weak activity biomarkers of AAV new molecules and factors start to come up, e.g.
      neutrophil extracellular traps NET, several T-lymphocyte subpopulations and
      different immunoglobulins classes of ANCA. In modern biological therapy rituximab
      is widely used, for refractory cases intravenous immunoglobulins and
      antithymocyte globulin are recommended. The data from clinical trials with
      alemtuzumab are controversial, but avacopan selective inhibitor of C5a receptor
      and inhibitor of B-lymphocyte activation factor belimumab are promise for
      future.Key words: biologicals - biomarkers - eosinophilic granulomatosis with
      polyangiitis - granulomatosis with polyangiitis - microscopic polyangiitis.

PMID- 29595282
TI  - [Diffuse alveolar hemorrhage - acute, life-threatening situation in
      rheumatology].
AB  - Diffuse alveolar hemorrhage (DAH) is a life-threatening acute manifestation of
      systemic diseases, the most commonly of systemic vasculitis. Clinically DAH
      manifests by a rapidly progressive respiratory and renal failure. The decisive
      for diagnose is immediate bronchoscopic examination with the bronchoalveolar
      lavage examination. CT mostly show bilateral pulmonary infiltrates, in blood
      picture rapidly come to anemia. In the majority of patients it can be found
      positive ANCA antibodies. DAH should be suspected in the case of acute
      respiratory failure also in patients without history of systemic disease. On the
      set of 33 patients with acute DAH episode, we demonstrate the importance of rapid
      diagnosis and aggressive therapy. In a third of our patients was DAH the first
      manifestation of systemic disease. Immunomodulatory treatment must be initiated
      immediately after diagnose. Hospital mortality in our group was 27 %, although 42
      % of the patients were required ventilation support and one-third of patients had
      acute renal failure. After handling of acute episode of DAH is the prognosis
      quoad vitam promising.Key words: bronchoalveolar fluid - diffuse alveolar
      haemorrhage - granulomatosis with polyangiitis - intensive care in rheumatology -
      vasculitis.

PMID- 29595283
TI  - [Polymyalgia rheumatica].
AB  - Polymyalgia rheumatica is the most frequent inflammatory disease of people over
      50 years of age. It mainly affects the Caucasian race and roughly 2-3 times as
      many women. From the viewpoint of etiology, polymyalgia rheumatica is a complex
      disease. Involved in its origin is genetic predisposition, factors of age and
      outer environment. 16-21 % of patients with polymyalgia rheumatica may at the
      same time have symptoms of giant cell arteritis. Diagnosis is made primarily on
      the basis of clinical symptoms and it is supported by the presence of laboratory
      signs of inflammation. There is no specific diagnostic test available for
      diagnosing polymyalgia rheumatica. In recent time modern imaging devices, e.g.
      ultrasonography or positron emission tomography, can be used in diagnosing the
      disease. In the past a number of diagnostic and classification criteria were
      established which may be used in diagnosing of polymyalgia rheumatica in general
      practice. The differential diagnostics of the disease is extensive. Before the
      treatment commencement it is necessary to rule out the presence of another
      disease with manifestations simulating polymyalgia rheumatica. The treatment
      strategy should draw on the current EULAR/ACR Recommendations for the treatment
      of polymyalgia rheumatica issued in 2015.Key words: polymyalgia rheumatica -
      positron emission tomography - prognosis - treatment - ultrasonography.

PMID- 29595284
TI  - [Treat to target in gouty arthritis].
AB  - Gout is a crystal-induced, metabolically determined inflammatory rheumatic
      disease with increasing prevalence. In clinical practice, gout causes frequent
      diagnostic as well as therapeutic problems. The golden diagnostic standard is
      crystalographic analysis and evidence of monosodium urate crystals in the
      polarization microscope; if this is not available, the diagnosis can be
      established through a combination of clinical, laboratory and imaging techniques.
      The acute gouty attack must be treated by quick administration of anti
      inflammatory medicines, with available alternatives being nonsteroidal
      antirheumatic drugs (NSA), colchicine and glucocorticoids. When the attack
      subsides, hypouricemic therapy is initiated which should combine the regimen and
      diet measures and pharmacological treatment. Recommendations for the treatment of
      gout were published by the EULAR and the Czech Society for Rheumatology. Recently
      a new strategy appeared known as Treat to target - T2T. This principle has been
      successfully used in the treatment of rheumatiod arthritis and spondyloarthritis.
      The publication is structured as four overarching principles and nine
      Recommendations. The recommendations emphasize long-term maintenance of serum
      levels of uric acid below 360 MUmol/l as the basic gout-related target in all
      patients, and below 300 MUmol/l for patients with tophies. It is recommended to
      administer prophylactic small doses of colchicine for at least 3-6 months on the
      commencement of hypouricemic therapy. The Recommendations further emphasize the
      need for regular monitoring of comorbidities and the kidney function. A separate
      recommendation is concerned with necessary education of patients and their
      motivation toward compliance with regimen measures and increased physical
      activity.Key words: colchicine - gouty arthritis - treat to target principle.

PMID- 29595285
TI  - [Nutraceuticals in therapy of knee osteoarthritis: orthopaedic view].
AB  - Knee osteoarthritis is one of the most frequent diagnoses of load-carrying joints
      encountered in orthopaedic surgeons offices. Depending on the clinical stage, the
      therapy starts with conservative treatment. Corrective osteotomy is indicated in
      younger patients without an extensive and serious impairment. Implantation of TKR
      (total knee replacement) is usually indicated in more advanced stages. One of the
      pillars of conservative therapy is analgesics and non-steroidal antirheumatic
      drugs. A specific group consists of perorally administered drugs for suppression
      of symptoms or even deceleration of knee osteoarthrosis. These products are
      popular mainly thanks to their good tolerance and minimal side effects. The
      clinical effect ranges between minimal and medium depending on the degree of
      osteoarthrosis, type of drug and study. Similar to rheumatologists, orthopaedic
      surgeons also find it difficult to identify candidates suitable for a particular
      type of therapy, except indication for TKR. By all means, nutraceuticals are
      still considered part of clinical practice.Key words: chondroitin sulphate -
      glucosamine sulphate - knee osteoarthrosis - methylsulfonylmethane -
      nutraceuticals - pharmaceutical intervention.

PMID- 29595286
TI  - [Osteoporosis and quality of bone].
AB  - The risk of osteoporotic fracture is determined collectively by bone mineral
      density, bone mass, architecture and properties of the mineral and organic matrix
      composite. Changes in these distinct aspects of quality of bone with age,
      estrogen deficiency, diseases leading to increased risk of fracture and
      differential mode of action of antiresorptive and bone anabolic treatments have
      to be considered in clinical therapeutic strategies. In patients at high risk of
      low impact fracture, sequential therapy switching to antiresorptives after
      patients have an adequate response to 2 years teriparatide may be the optimal
      strategy of long term therapy.Key words: aging - bone quality - osteoporosis -
      prevention - therapy.

PMID- 29595288
TI  - Drawing inferences from emotion expressions: The role of situative
      informativeness and context.
AB  - How people react emotionally to an event can tell us much about the event itself.
      However, emotions vary in their situative informativeness, that is, in how much
      information about the situation they provide. We predicted that when emotions are
      shown that are low in situative informativeness participants rely more on context
      information, then when the emotions shown are high in situative informativeness.
      This hypothesis was tested in 2 studies in which participants were asked to
      evaluate the quality of a player's performance based on the emotional reactions
      of spectators to an unknown ball game. Spectators reacted either with awe (high
      in situative informativeness), or with happiness or neutrality (low in situative
      informativeness). Participant also received context information. The findings
      supported the predictions and illustrate how emotions and context interact to
      inform us about events. (PsycINFO Database Record

PMID- 29595287
TI  - Perceptions of belongingness and social support attenuate PTSD symptom severity
      among firefighters: A multistudy investigation.
AB  - Firefighters experience high rates of posttraumatic stress disorder (PTSD). It is
      imperative to identify malleable factors that protect against the development of
      PTSD symptoms among this population. We examined whether perceptions of
      belongingness broadly (Study 1) and social support from supervisors, coworkers,
      and family/friends specifically (Study 2) are associated with lower PTSD symptom
      severity among firefighters. Study 1 included 840 U.S. firefighters (91.1% male);
      participants completed the Interpersonal Needs Questionnaire and PTSD Checklist
      Civilian Version. Study 2 included 200 U.S. women firefighters exposed to a
      Criterion A traumatic event; participants completed the Generic Job Stress
      Questionnaire, Life Events Checklist for Diagnostic and Statistical Manual of
      Mental Disorders-5, and PTSD Checklist for Diagnostic and Statistical Manual of
      Mental Disorders-5. Linear regression analyses were conducted, adjusting for the
      number of years participants served as firefighters. Greater belongingness
      broadly (Study 1; b = -0.740, p < .001) as well as social support specifically
      (Study 2) from supervisors (b = -4.615, p < .001), coworkers (b = -4.465, p =
      .001), and family/friends (b = -3.206, p = .021) were associated with less severe
      PTSD symptoms. When all sources of social support were entered into a single
      model, only support from supervisors was significantly associated with lower
      overall PTSD symptom severity (b = -4.222, p = .004). Belongingness and social
      support may protect against the development of PTSD among firefighters.
      Supervisor social support may be particularly salubrious, suggesting that top
      down mental wellness promotion within the fire service may be indicated to
      protect firefighters against PTSD. (PsycINFO Database Record

PMID- 29595289
TI  - Daily micro-breaks and job performance: General work engagement as a cross-level
      moderator.
AB  - Despite the growing research on work recovery and its well-being outcomes,
      surprisingly little attention has been paid to at-work recovery and its job
      performance outcomes. The current study extends the work recovery literature by
      examining day-level relationships between prototypical microbreaks and job
      performance as mediated by state positive affect. Furthermore, general work
      engagement is tested as a cross-level moderator weakening the indirect effects of
      microbreaks on job performance via positive affect. Using multisource experience
      sampling method, the authors collected two daily surveys from 71 call center
      employees and obtained objective records of daily sales performance for two
      consecutive weeks (n = 632). Multilevel path analysis results showed that
      relaxation, socialization, and cognitive microbreaks were related to increased
      positive affect at work which, in turn, predicted greater sales performance.
      However, breaks for nutrition-intake (having snacks and drinks) did not show
      significant effects. Importantly, microbreaks had significant indirect effects on
      job performance via positive affect only for workers who had lower general work
      engagement, whereas the indirect effects did not exist for workers who had higher
      general work engagement. Furthermore, Bayesian multilevel analyses confirmed the
      results. Theoretical and practical implications, limitations, and future research
      directions are discussed. (PsycINFO Database Record

PMID- 29595290
TI  - Parental executive function and verbal ability matter for scaffolding.
AB  - Despite the importance of parental scaffolding for later child cognitive outcomes
      and academic achievement, sources of individual variation in scaffolding are not
      fully understood. Scaffolding places extensive demands on cognitive capacity,
      including planning, flexibly shifting, and inhibition. Executive function (EF) is
      therefore a parental cognitive ability especially important for effective
      scaffolding. In this study, parents and preschool-aged children completed a
      challenging puzzle to assess scaffolding. EF and verbal ability were measured for
      parents and children. Parental verbal ability was used as an index of global
      higher-order cognitive function. Higher levels of parental EF related to more
      effective scaffolding, above and beyond parental verbal ability and independent
      of child cognitive level. These results highlight the significance of considering
      parental cognitive capacities in future studies to better understand the sources
      of individual differences in scaffolding. (PsycINFO Database Record

PMID- 29595291
TI  - Method biases in single-source personality assessments.
AB  - The magnitude of components of variance in trait scales-true score, method
      variance, and error-can be estimated from information on the mono-method
      correlations among personality traits within a domain and on cross-observer
      agreement on domains and facets. Estimates of these components in NEO Inventory
      facet scales were compared with prior estimates that were based on a
      consideration of internal consistency and retest reliability (McCrae, 2015).
      Together, results suggested that (a) about 40% of the variance in self-reports
      and single informant ratings is due to method variance; (b) as with substantive
      traits, method biases exist on several different levels, some broad, some narrow;
      and (c) consequently, a large number of distinct biases affect personality scale
      scores. Method biases beyond acquiescence and evaluation were also found in a
      clinical instrument, the Personality Inventory for DSM-5. Because many biases
      appear to be idiosyncratic, it is unlikely that validity scales could be created
      to assess or control all of them. These findings underscore the value of
      utilizing multiple informants in research and individual assessment. To the
      extent that they can be distinguished from valid variance, method biases are
      themselves of clinical interest as potentially important elements of the self
      concept. (PsycINFO Database Record

PMID- 29595292
TI  - Imaginary alternatives: The effects of mental simulation on powerless
      negotiators.
AB  - This research demonstrates that people can act more powerfully without having
      power. Researchers and practitioners advise people to obtain alternatives in
      social exchange relationships to enhance their power. However, alternatives are
      not always readily available, often forcing people to interact without having
      much power. Building on research suggesting that subjective power and objective
      outcomes are disconnected and that mental simulation can improve aspirations, we
      show that the mental imagery of a strong alternative can provide some of the
      benefits that real alternatives provide. We tested this hypothesis in one context
      of social exchange-negotiations-and demonstrate that imagining strong
      alternatives (vs. not) causes powerless individuals to negotiate more
      ambitiously. Negotiators reached more profitable agreements when they had a
      stronger tendency to simulate alternatives (Study 1) or when they were instructed
      to simulate an alternative (Studies 3-6). Mediation analyses suggest that mental
      simulation enhanced performance because it boosted negotiators' aspirations and
      subsequent first offers (Studies 2-6), but only when the simulated alternative
      was attractive (Study 5). We used various negotiation contexts, which also
      allowed us to identify important boundary conditions of mental simulations in
      interdependent settings: mental simulation no longer helped when negotiators did
      not make the first offer, when their opponents simultaneously engaged in mental
      simulation (Study 6), and even backfired in settings where negotiators' positions
      were difficult to reconcile (Study 7). An internal meta-analysis of the file
      drawer produces conservative effect size estimates and demonstrates the
      robustness of the effect. We contribute to social power, negotiations, and mental
      simulation research. (PsycINFO Database Record

PMID- 29595293
TI  - A tutorial on regularized partial correlation networks.
AB  - Recent years have seen an emergence of network modeling applied to moods,
      attitudes, and problems in the realm of psychology. In this framework,
      psychological variables are understood to directly affect each other rather than
      being caused by an unobserved latent entity. In this tutorial, we introduce the
      reader to estimating the most popular network model for psychological data: the
      partial correlation network. We describe how regularization techniques can be
      used to efficiently estimate a parsimonious and interpretable network structure
      in psychological data. We show how to perform these analyses in R and demonstrate
      the method in an empirical example on posttraumatic stress disorder data. In
      addition, we discuss the effect of the hyperparameter that needs to be manually
      set by the researcher, how to handle non-normal data, how to determine the
      required sample size for a network analysis, and provide a checklist with
      potential solutions for problems that can arise when estimating regularized
      partial correlation networks. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29595295
TI  - Hierarchical Bayesian continuous time dynamic modeling.
AB  - Continuous time dynamic models are similar to popular discrete time models such
      as autoregressive cross-lagged models, but through use of stochastic differential
      equations can accurately account for differences in time intervals between
      measurements, and more parsimoniously specify complex dynamics. As such they
      offer powerful and flexible approaches to understand ongoing psychological
      processes and interventions, and allow for measurements to be taken a variable
      number of times, and at irregular intervals. However, limited developments have
      taken place regarding the use of continuous time models in a fully hierarchical
      context, in which all model parameters are allowed to vary over individuals. This
      has meant that questions regarding individual differences in parameters have had
      to rely on single-subject time series approaches, which require far more
      measurement occasions per individual. We present a hierarchical Bayesian approach
      to estimating continuous time dynamic models, allowing for individual variation
      in all model parameters. We also describe an extension to the ctsem package for
      R, which interfaces to the Stan software and allows simple specification and
      fitting of such models. To demonstrate the approach, we use a subsample from the
      German socioeconomic panel and relate overall life satisfaction and satisfaction
      with health. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29595294
TI  - Benchmark validation of statistical models: Application to mediation analysis of
      imagery and memory.
AB  - This article describes benchmark validation, an approach to validating a
      statistical model. According to benchmark validation, a valid model generates
      estimates and research conclusions consistent with a known substantive effect.
      Three types of benchmark validation-(a) benchmark value, (b) benchmark estimate,
      and (c) benchmark effect-are described and illustrated with examples. Benchmark
      validation methods are especially useful for statistical models with assumptions
      that are untestable or very difficult to test. Benchmark effect validation
      methods were applied to evaluate statistical mediation analysis in eight studies
      using the established effect that increasing mental imagery improves recall of
      words. Statistical mediation analysis led to conclusions about mediation that
      were consistent with established theory that increased imagery leads to increased
      word recall. Benchmark validation based on established substantive theory is
      discussed as a general way to investigate characteristics of statistical models
      and a complement to mathematical proof and statistical simulation. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 29595296
TI  - Determining synchrony between behavioral time series: An application of surrogate
      data generation for establishing falsifiable null-hypotheses.
AB  - Synchrony between interacting systems is an important area of nonlinear dynamics
      in physical systems. Recently psychological researchers from multiple areas of
      psychology have become interested in nonverbal synchrony (i.e., coordinated
      motion between two individuals engaged in dyadic information exchange such as
      communication or dance) as a predictor and outcome of psychological processes. An
      important step in studying nonverbal synchrony is systematically and validly
      differentiating synchronous systems from nonsynchronous systems. However, many
      current methods of testing and quantifying nonverbal synchrony will show some
      level of observed synchrony even when research participants have not interacted
      with one another. In this article we demonstrate the use of surrogate data
      generation methodology as a means of testing new null-hypotheses for synchrony
      between bivariate time series such as those derived from modern motion tracking
      methods. Hypotheses generated by surrogate data generation methods are more
      nuanced and meaningful than hypotheses from standard null-hypothesis testing. We
      review four surrogate data generation methods for testing for significant
      nonverbal synchrony within a windowed cross-correlation (WCC) framework. We also
      interpret the null-hypotheses generated by these surrogate data generation
      methods with respect to nonverbal synchrony as a specific use of surrogate data
      generation, which can then be generalized for hypothesis testing of other
      psychological time series. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29595297
TI  - Alcohol, cannabis, and other drug use: Engagement and outcome in PTSD treatment.
AB  - The co-occurrence of posttraumatic stress disorder (PTSD) and substance use is
      related to poorer outcome and increased dropout from trauma-focused treatment.
      Investigating PTSD and substance use can inform the intervention approaches.
      Exploring cannabis use in particular is especially important because rates of
      cannabis use have been increasing with recent legalization trends. A better
      understanding of how substance use is associated with treatment processes and
      outcome for individuals with PTSD is needed to enhance care. In this study, both
      lifetime diagnoses of alcohol and drug use disorders and current alcohol and drug
      use severity were examined in 200 men and women with chronic PTSD who received
      either prolonged exposure (PE) or sertraline. No lifetime or current alcohol use
      variables predicted dropout, adherence, or poorer outcome. However, lifetime
      diagnosis of both an alcohol and drug disorder (OR = 3.42) and recent cannabis
      use (OR = 3.38) strongly predicted higher dropout. Recent cannabis use and drug
      use severity predicted poorer adherence to PE (beta = -.22 to -.29) but not to
      sertraline. Drug use severity (beta = -.22) also predicted worse treatment
      outcome, as did lifetime diagnosis of an alcohol and drug disorder (beta = -.48).
      Overall, patients with drug use improved with treatment but had less treatment
      retention, adherence, and symptom reduction. Strategies to increase engagement
      and retention may be indicated for these patients. Individuals who are using
      cannabis or other drugs may be at higher risk for not completing PTSD treatment,
      potentially prolonging the cycle of PTSD and substance use. (PsycINFO Database
      Record

PMID- 29595299
TI  - Staying positive in a dystopian future: A novel dissociation between personal and
      collective cognition.
AB  - The future of groups of people is a topic of broad interest in society and
      academia. Nonetheless, relatively little is known about the manner in which
      people think about the collective future of groups, and whether personal and
      collective future thinking represent distinct domains of future-oriented
      cognition. In the present studies (N = 691), we used an adapted future fluency
      task to demonstrate a novel domain-by-valence interaction between personal and
      collective future thinking, such that U.S.-based participants were positively
      biased about their personal future while at the same time being negatively biased
      about the future of their country. We further present evidence that this valence
      based dissociation extends into the distant future, emerges in a non-U.S.
      (Canadian) sample, depends on the individual's relation to the group, and has
      consequences for how people think about the world around them. Taken together,
      our findings represent the first behavioral evidence of a dissociation between
      personal and collective future thinking, and suggest that the study of collective
      future thinking represents a fruitful endeavor for psychological science.
      (PsycINFO Database Record

PMID- 29595298
TI  - Decision-making and socioeconomic disparities in colonoscopy screening in African
      Americans.
AB  - BACKGROUND: Socioeconomic status (SES) disparities in colorectal cancer screening
      are persistent. Lower education and income are both associated with lower
      screening rates. Both cognitive (e.g., perceived barriers) and affective (e.g.,
      disgust, fear) decision-making constructs are known determinants of colorectal
      cancer screening behavior. This study tests the hypotheses that SES may be
      related to decision-making constructs and that this SES-decision-making construct
      relation may contribute to explaining the SES-screening behavior disparity.
      METHOD: Surveys assessing perceived benefits and barriers to screening, self
      efficacy, positive and negative affective associations with colonoscopy, fear of
      colonoscopy, colorectal cancer knowledge, past screening behavior, and
      demographics including education and income were completed by 2,015 African
      American participants ages 50 and older. Both univariable and multivariable
      relations of SES to decision-making constructs were examined, as were univariable
      and multivariable models of the indirect effect of SES on screening via decision
      making constructs. RESULTS: Socioeconomic status was related to both screening
      compliance and the decision-making constructs. Bootstrap modeling of the indirect
      effect showed that the total effect of the SES-screening behavior relation
      included an indirect effect via social cognitive decision-making constructs.
      CONCLUSION: These findings suggest that cognitive and affective decision-making
      constructs account for at least some of the SES disparities in colorectal cancer
      screening behavior. As such, more research is needed to explore the intra
      individual-level influences of disparities in colorectal cancer screening. In
      addition, work is needed to develop effective intervention approaches to address
      the relation of SES to decision-making constructs. (PsycINFO Database Record

PMID- 29595300
TI  - "Narrowing the transmission gap: A synthesis of three decades of research on
      intergenerational transmission of attachment": Correction.
AB  - Reports an error in "Narrowing the transmission gap: A synthesis of three decades
      of research on intergenerational transmission of attachment" by Marije L.
      Verhage, Carlo Schuengel, Sheri Madigan, R. M. Pasco Fearon, Mirjam Oosterman,
      Rosalinda Cassibba, Marian J. Bakermans-Kranenburg and Marinus H. van IJzendoorn
      (Psychological Bulletin, 2016[Apr], Vol 142[4], 337-366). In the article, there
      are errors in Table 7. The percentages of the attachment classifications do not
      add up to 100%. The corrected version of Table 7 is provided in the erratum. (The
      following abstract of the original article appeared in record 2015-55801-001.)
      Twenty years ago, meta-analytic results (k = 19) confirmed the association
      between caregiver attachment representations and child-caregiver attachment (Van
      IJzendoorn, 1995). A test of caregiver sensitivity as the mechanism behind this
      intergenerational transmission showed an intriguing "transmission gap." Since
      then, the intergenerational transmission of attachment and the transmission gap
      have been studied extensively, and now extend to diverse populations from all
      over the globe. Two decades later, the current review revisited the effect sizes
      of intergenerational transmission, the heterogeneity of the transmission effects,
      and the size of the transmission gap. Analyses were carried out with a total of
      95 samples (total N = 4,819). All analyses confirmed intergenerational
      transmission of attachment, with larger effect sizes for secure-autonomous
      transmission (r = .31) than for unresolved transmission (r = .21), albeit with
      significantly smaller effect sizes than 2 decades earlier (r = .47 and r = .31,
      respectively). Effect sizes were moderated by risk status of the sample,
      biological relatedness of child-caregiver dyads, and age of the children.
      Multivariate moderator analyses showed that unpublished and more recent studies
      had smaller effect sizes than published and older studies. Path analyses showed
      that the transmission could not be fully explained by caregiver sensitivity, with
      more recent studies narrowing but not bridging the "transmission gap."
      Implications for attachment theory as well as future directions for research are
      discussed. (PsycINFO Database Record

PMID- 29595301
TI  - Publishing papers that matter.
AB  - Daniel G. Morrow introduces himself as the fifth editor of the Journal of
      Experimental Psychology: Applied (JEPA). The journal is the premier outlet for
      "use-inspired basic research" (Stokes, 2011) in the psychological sciences.
      (PsycINFO Database Record

PMID- 29595302
TI  - Communicating weather forecast uncertainty: Do individual differences matter?
AB  - Research suggests that people make better weather-related decisions when they are
      given numeric probabilities for critical outcomes (Joslyn & Leclerc, 2012, 2013).
      However, it is unclear whether all users can take advantage of probabilistic
      forecasts to the same extent. The research reported here assessed key cognitive
      and demographic factors to determine their relationship to the use of
      probabilistic forecasts to improve decision quality. In two studies, participants
      decided between spending resources to prevent icy conditions on roadways or risk
      a larger penalty when freezing temperatures occurred. Several forecast formats
      were tested, including a control condition with the night-time low temperature
      alone and experimental conditions that also included the probability of freezing
      and advice based on expected value. All but those with extremely low numeracy
      scores made better decisions with probabilistic forecasts. Importantly, no groups
      made worse decisions when probabilities were included. Moreover, numeracy was the
      best predictor of decision quality, regardless of forecast format, suggesting
      that the advantage may extend beyond understanding the forecast to general
      decision strategy issues. This research adds to a growing body of evidence that
      numerical uncertainty estimates may be an effective way to communicate weather
      danger to general public end users. (PsycINFO Database Record

PMID- 29595303
TI  - The effects of prequestions on classroom learning.
AB  - Studies have shown that prequestions-asking students questions before they learn
      something-benefit memory retention. Prequestions would seem to be a useful
      technique for enhancing students' learning in their courses, but classroom
      investigations of prequestions have been sparse. In the current study, students
      from an introductory psychology course were randomly assigned to receive
      prequestions over each upcoming lesson (prequestion group) or to not receive
      prequestions (control group). At the end of class, students in the prequestion
      group remembered the material better than students in the control group, but this
      benefit was specific to the information that was asked about in the prequestions.
      When memory for other, nonprequestioned portions of the lesson were tested at the
      end of class, the prequestion group performed similarly to the control group. On
      a follow-up quiz 1 week later, both groups showed a memory advantage for material
      that was tested at the end of class 1 week prior, compared with information from
      the same lesson that was never tested. However, this benefit was comparable
      between the prequestion group and the control group, suggesting that students
      benefit from retrieval practice, but prequestions add little, if any, enhancement
      to this effect. (PsycINFO Database Record

PMID- 29595304
TI  - Future self-continuity is associated with improved health and increases exercise
      behavior.
AB  - To the extent that people feel more continuity between their present and future
      selves, they are more likely to make decisions with the future self in mind. The
      current studies examined future self-continuity in the context of health. In
      Study 1, people reported the extent to which they felt similar and connected to
      their future self; people with more present-future continuity reported having
      better subjective health across a variety of measures. In Study 2, people were
      randomly assigned to write a letter to themselves either three months or 20 years
      into the future; people for whom continuity with the distant future self was
      enhanced exercised more in the days following the writing task. These findings
      suggest that future self-continuity promotes adaptive long-term health behavior,
      suggesting the promise of interventions enhancing future self-continuity.
      (PsycINFO Database Record

PMID- 29595305
TI  - Self-persuasion in media messages: Reducing alcohol consumption among students
      with open-ended questions.
AB  - Self-persuasion (self-generation of arguments) is often a more effective
      influence technique than direct persuasion (providing arguments). However, the
      application of this technique in health media communications has received limited
      attention. In two experiments, it was examined whether self-persuasion can be
      successfully applied to antialcohol media communications by framing the message
      as an open-ended question. In Experiment 1 (N = 131) cognitive reactions to
      antialcohol posters framed either as open-ended questions or statements were
      examined. In Experiment 2 (N = 122) the effectiveness of this framing to reduce
      actual alcohol consumption was tested. Experiment 1 demonstrated that exposure to
      an antialcohol poster framed as an open-ended question resulted in more self
      generated arguments for drinking less alcohol and more favorable message
      evaluations than framing the same message as a statement. Experiment 2 showed
      that the self-persuasion poster did not affect the choice to consume alcohol but
      did reduce alcohol consumption for individuals who chose to drink any alcohol,
      compared with a direct persuasion poster or no intervention. Together, the
      results demonstrated the potential of self-persuasion in persuasive media
      messages for interventions aimed at alcohol consumption reduction specifically
      and for health communication in general. (PsycINFO Database Record

PMID- 29595306
TI  - Sensory substitution: Using a vibrotactile device to orient and walk to targets.
AB  - This study investigates how active exploration helps users of sensory
      substitution devices (SSDs) to detect action-relevant information. A vibrotactile
      SSD was developed that generates stimulation that is contingent on the users'
      movements. Target direction was specified by the location of the vibratory
      stimulation, and target distance by the size and intensity of the pattern of
      stimulation. A series of experiments was performed with blindfolded participants.
      In Experiments 1a to 1c, participants used the SSD to align their central body
      axis with prespecified targets. These experiments differed in the number of
      actuators that were used and whether online perception-action coupling was
      present. In Experiment 2, participants approached targets with forward locomotion
      along a straight line. Experiment 3 combined the previous experiments and studied
      the concomitant walking and steering toward targets. Oscillatory movements, which
      facilitated information pickup, were observed in all experiments. The exploratory
      oscillations were shown to depend on the online perception-action coupling and
      were related to cases of hyperacuity, for which absolute errors were found to be
      smaller than the areas of sensitivity of the actuators. It is concluded that, to
      improve the utility of SSDs, future research with SSDs should pay more attention
      to the role of active information detection. (PsycINFO Database Record

PMID- 29595307
TI  - Night awakening in infancy: Developmental stability and longitudinal associations
      with psychomotor development.
AB  - Fragmented sleep is common in infancy. Although night awakening is known to
      decrease with age, in some infants night awakening is more persistent and
      continues into older ages. However, the influence of fragmented sleep on
      development is poorly known. In the present study, the longitudinal relationship
      between fragmented sleep and psychomotor development (Bayley Scales of Infant and
      Toddler Development [Bayley-III]; Bayley, 2009) was investigated in infants with
      (>=3 night awakenings, n = 81) and without fragmented sleep (<=1 night awakening,
      n = 70) within the CHILD-SLEEP birth cohort at 8 and 24 months of age.
      Differences in parent-reported (Brief Infant Sleep Questionnaire [BISQ]) sleep
      parameters were studied at 8, 18, and 24 months of age. Group differences in
      night awakening were stable across all assessment points. Infants with fragmented
      sleep slept less in total than infants without fragmented sleep and they did not
      compensate their nocturnal sleep during daytime. Additionally, infants with
      fragmented sleep spent more time awake at night than infants without fragmented
      sleep. However, psychomotor development did not differ between infants with and
      without fragmented sleep at 8 or 24 months of age. Our findings indicate that
      early onset fragmented sleep did not have a negative effect on psychomotor
      development within the first 2 years despite the differences in sleep length
      among infants with and without fragmented sleep. In the future, more specific
      domains of cognitive development and various factors affecting sleep
      fragmentation should be taken into account when studying the developmental
      effects of night awakening in infancy. (PsycINFO Database Record

PMID- 29595308
TI  - The association between religiousness and children's altruism: The role of the
      recipient's neediness.
AB  - We examined the role of the recipient's neediness as a moderator in the relation
      between children's household religiosity and prosocial behavior. Examining the
      behavior of children (2nd and 5th graders) from religious and nonreligious
      households in the dictator game, we found that the extent of sharing did not
      differ significantly between the 2 groups when the recipient was not described as
      needy. However, when the recipient was presented as a poor (needy) child, the
      religious group exhibited significantly more sharing behavior. Although the
      religious children's tendency to share more with needy recipients compared with
      the not-needy ones appeared already in the 2nd grade, it increased with age as
      children grew and internalized the norms of their immediate society. Among the
      major religions, the recipient's neediness is an important variable in the
      decision to give, which shapes religious children's prosocial behavior from an
      early age. Thus, future research should take this moderator into account when
      studying the relation between religiousness and prosociality in general and in
      the development of prosociality in children in particular. (PsycINFO Database
      Record

PMID- 29595309
TI  - Feeling loved and integrated or lonely and rejected in everyday life: The role of
      age and social motivation.
AB  - Social approach and social avoidance goals (i.e., approach of positive and
      avoidance of negative outcomes in social situations) are important predictors of
      the feeling of being socially integrated or isolated. However, little is known
      about the development of these goals across adulthood. In a large diary study
      with N = 744 young (18-39 years), middle-aged (40-59 years), and older adults (60
      83 years), we tested the hypothesis that the adaptiveness of social goals changes
      across adulthood: Social approach goals were hypothesized to be adaptive during
      young adulthood when adult social relationships are to be established. In
      contrast, social avoidance goals were hypothesized to become more adaptive with
      age as people are increasingly motivated to avoid interpersonal tension. Our
      findings support these hypotheses: Social approach goals were positively and
      social avoidance goals negatively associated with younger but not with middle
      aged and older adults' daily social well-being. These results were robust across
      different situations (positive, negative) and different types of relationships
      (close, peripheral). The study highlights the changing role of social approach
      and avoidance goals for daily social well-being across adulthood. (PsycINFO
      Database Record

PMID- 29595310
TI  - From map reading to geometric intuitions.
AB  - The origins and development of our geometric intuitions have been debated for
      millennia. The present study links children's developing intuitions about the
      properties of planar triangles to their developing abilities to read purely
      geometric maps. Six-year-old children are limited when navigating by maps that
      depict only the sides of a triangle in an environment composed of only the
      triangle's corners and vice versa. Six-year-old children also incorrectly judge
      how the angle size of the third corner of a triangle varies with changes to the
      other two corners. These limitations in map reading and in judgments about
      triangles are attenuated, respectively, by 10 and 12 years of age. Moreover, as
      children get older, their map reading predicts their geometric judgments on the
      triangle task. Map reading thus undergoes developmental changes that parallel an
      emerging capacity to reason explicitly about the distance and angle relations
      essential to euclidean geometry. (PsycINFO Database Record

PMID- 29595311
TI  - The effects of shared storybook reading on word learning: A meta-analysis.
AB  - Although an abundant literature documents preliterate children's word learning
      success from shared storybook reading, a full synthesis of the factors which
      moderate these word learning effects has been largely neglected. This meta
      analysis included 38 studies with 2,455 children, reflecting 110 effect sizes,
      investigating how reading styles, story repetitions, tokens and related factors
      moderate children's word comprehension, while adjusting for the number of target
      words. Dialogic reading styles, tokens, and the number of words tested all
      moderated word learning effects. Children's age, who read the story, and time
      between story and test were not moderators. We identify story repetition and word
      types as topics which merit further research. These results provide information
      to guide researchers and educators alike to the factors with the greatest impact
      on improving word learning from shared storybook reading. (PsycINFO Database
      Record

PMID- 29595313
TI  - You don't need to talk to throw a ball! Children's inclusion of language-outgroup
      members in behavioral and hypothetical scenarios.
AB  - To investigate children's inclusion of language-outgroup members, English
      speaking children (8-9 years and 10-11 years of age, N = 57) made inclusion
      decisions while playing a simulated ball-tossing game, Cyberball, and while
      evaluating hypothetical scenarios involving language-outgroup members who wanted
      to play with their group. In the Cyberball game, the group norm was to exclude
      non-English-speaking peers, and participant tosses to a language-outgroup member
      (i.e., Spanish, Chinese, or Arabic speaking) were coded as a measure of
      behavioral inclusion. In the hypothetical scenarios, participants made
      prescriptive and descriptive judgments about their expectations regarding the
      inclusion of a language-outgroup member. They also evaluated their own and their
      group's inclusion likelihood. Results revealed that participants' evaluations of
      how acceptable exclusion was predicted their behavioral inclusion in the
      Cyberball game. Further, participants were more likely to think that the language
      outgroup member should be included and less likely to think that the outgroup
      member would be included. They also differentiated between their own and their
      group's likelihood of including a language-outgroup member and reasoned about
      this decision by focusing on group functioning and language. In addition, there
      were age-related differences, with participants demonstrating greater inclusivity
      with age. The findings suggest the complexity of children's social cognition and
      the importance of providing them with a rich array of opportunities to play with
      language-outgroup members. (PsycINFO Database Record

PMID- 29595312
TI  - CPS-referred mothers' psychophysiological responses to own versus other child
      predict sensitivity to child distress.
AB  - Maltreating mothers often struggle to respond sensitively to their children's
      distress. Examining psychophysiological processing of own child cues may offer
      insight into neurobiological mechanisms that promote sensitive parenting among
      high-risk mothers. The current study used event-related potential (ERP)
      methodology to examine associations between mothers' neural responses to their
      own child versus other children and observed sensitivity to distress.
      Participants included 73 mothers: 42 with histories of child protective services
      (CPS) involvement and 31 low-risk comparison mothers. Maternal sensitivity to
      child distress was coded from observations of children's blood sample collection.
      Late positive potential (LPP) ERP responses, which reflect sustained attention to
      emotionally salient stimuli, were measured when mothers viewed photos of their
      own child and other children. An own-other LPP difference score (own-other LPP)
      was computed by regressing the mean amplitude of mothers' LPP to their own child
      on the mean amplitude of mothers' LPP to other children. CPS-referred mothers and
      low-risk mothers did not differ in their LPP responses to own child, other
      children, or the own-other LPP. However, there was a significant interaction
      between group (CPS-referred vs. low-risk) and own-other LPP in predicting
      maternal sensitivity. Among the CPS-referred mothers, own-other LPP was
      significantly correlated with maternal sensitivity, with greater LPP amplitude to
      own versus other child associated with higher maternal sensitivity. In contrast,
      among the low-risk group, own-other LPP was not significantly correlated with
      maternal sensitivity. Findings add to our understanding of the neurobiology of
      sensitive parenting among high-risk mothers. (PsycINFO Database Record

PMID- 29595315
TI  - The Revised College of American Pathologists/International Association for the
      Study of Lung Cancer/Association for Molecular Pathology Guideline: A Step
      Forward for Molecular Cytopathology.

PMID- 29595314
TI  - Trajectories of cannabis-related associative memory among vulnerable adolescents:
      Psychometric and longitudinal evaluations.
AB  - Indirect tests of memory associations relevant to cannabis have been shown to be
      useful in explaining and predicting adolescent cannabis use habits. This study
      sought to increase the understanding of adolescent cannabis-related associative
      memory and cannabis use behavior over time. A longitudinal sample of alternative
      high school students (N = 775) was assessed yearly for 3 years. The study first
      conducted extensive longitudinal measurement analyses of the cannabis-related
      word association test (WAT) applying contemporary psychometric models. Second,
      the study examined the longitudinal trajectories of cannabis-related associative
      memory and cannabis use and their contemporaneous and longitudinal relationships.
      Results showed that the cannabis-related WAT provided strong evidence of sound
      psychometric properties. Longitudinal change in cannabis-related associative
      memory was best described by modeling either a linearly decreasing trajectory or
      two separate trajectories: During middle adolescence, levels of cannabis-related
      associative memory were highest and stable but then gradually decreased toward
      late adolescence. Moreover, cannabis-related associative memory was
      contemporaneously predictive of cannabis use within ages 15 to 19 while
      controlling for the underlying growth process of cannabis use and time-invariant
      covariates (TICs) of gender and lifetime concurrent use of alcohol and
      cigarettes. Partial support of longitudinal prediction of cannabis use was also
      obtained from age 17 to 18 and age 19 to 20 while adjusting for growth in
      cannabis use and the TICs. These results demonstrated that predictive effects of
      cannabis-related memory associations on cannabis use were detected within some of
      the 1-year age spans and were consistent within ages across adolescent years.
      (PsycINFO Database Record

PMID- 29595316
TI  - Double-Equivocal HER2 Invasive Breast Carcinomas: Institutional Experience and
      Review of Literature.
AB  - CONTEXT.-: HER2 status is a prognostic factor and therapeutic target in invasive
      breast carcinomas. Reflex testing using an alternate method is recommended on
      equivocal cases via immunohistochemistry or fluorescence in situ hybridization
      (FISH). Therapeutic dilemmas arise when both tests are equivocal. The standard
      chromosome 17 centromere reference probe (CEP17) is in close proximity to the
      HER2 locus and may be coamplified, leading to equivocal results. Alternate
      chromosome 17 reference probes may aid in establishing the true HER2 status.
      OBJECTIVE.-: To describe our institutional experience using D17S122 probe for
      reflex FISH testing on double-equivocal invasive breast carcinomas and review the
      literature on alternate reference probes. DATA SOURCES.-: Twenty-two patients
      with double-equivocal invasive breast carcinomas, defined as HER2
      immunohistochemistry score 2+ and FISH equivocal per the 2013 guidelines, were
      reviewed. Reflex FISH was performed with alternate probe D17S122 and the HER2
      status classified for 11 cases by using a revised HER2: D17S122 ratio. Seven of
      11 cases (63.6%) were ultimately classified as HER2 positive, while 4 cases
      (36.4%) remained equivocal. The 7 positive cases showed a HER2: D17S122 greater
      than 2.0. CONCLUSIONS.-: Alternate probe D17S122 reclassified more than half of
      our cases as HER2 positive. Alternate probes may establish true HER2 status and
      direct proper management, as evidenced by our experience and the literature.
      Additional investigation is needed to determine which alternate probe(s) is(are)
      best for reflex testing. Finally, the American Society of Clinical
      Oncology/College of American Pathologists guidelines may need to be updated to
      reflect more specific recommendations for the utilization of appropriate probes
      in double-equivocal HER2 cases.

PMID- 29595318
TI  - Single Genes, Panels, and Next-Generation Sequencing Platforms: A Financial
      Perspective.

PMID- 29595317
TI  - Quantitative Assessment of Immunohistochemistry Laboratory Performance by
      Measuring Analytic Response Curves and Limits of Detection.
AB  - CONTEXT: - Numerous studies highlight interlaboratory performance variability in
      diagnostic immunohistochemistry (IHC) testing. Despite substantial improvements
      over the years, the inability to quantitatively and objectively assess
      immunostain sensitivity complicates interlaboratory standardization. OBJECTIVE: -
      To quantitatively and objectively assess the sensitivity of the
      immunohistochemical stains for human epidermal growth factor receptor type 2
      (HER2), estrogen receptor (ER), and progesterone receptor (PR) across IHC
      laboratories in a proficiency testing format. We measure sensitivity with
      parameters that are new to the field of diagnostic IHC: analytic response curves
      and limits of detection. DESIGN: - Thirty-nine diagnostic IHC laboratories
      stained a set of 3 slides, one each for HER2, ER, and PR. Each slide incorporated
      a positive tissue section and IHControls at 5 different concentrations. The
      IHControls comprise cell-sized clear microbeads coated with defined
      concentrations of analyte (HER2, ER, and/or PR). The laboratories identified the
      limits of detection and then mailed the slides for quantitative assessment.
      RESULTS: - Each commercial immunostain demonstrated a characteristic analytic
      response curve, reflecting strong reproducibility among IHC laboratories using
      the same automation and reagents prepared per current Good Manufacturing
      Practices. However, when comparing different commercial vendors (using different
      reagents), the data reveal up to 100-fold differences in analytic sensitivity.
      For proficiency testing purposes, quantitative assessment using analytic response
      curves was superior to subjective interpretation of limits of detection.
      CONCLUSIONS: - Assessment of IHC laboratory performance by quantitative
      measurement of analytic response curves is a powerful, objective tool for
      identifying outlier IHC laboratories. It uniquely evaluates immunostain
      performance across a range of defined analyte concentrations.

PMID- 29595319
TI  - Electroconvulsive therapy in a patient with metallic implant.

PMID- 29595320
TI  - Thyroid nodules and cancer in children and adolescents affected by Hashimoto's
      thyroiditis.
AB  - OBJECTIVE: To investigate the rates of thyroid nodules and cancer in pediatric
      cases of Hashimoto's thyroiditis (HT) in Korea. METHODS: We retrospectively
      reviewed 89 pediatric and adolescent patients (age, 3-18.0 years) with HT who
      underwent thyroid ultrasonography (US) at our institution from February 2006 to
      July 2016. The diagnosis of HT was based on the presence of thyroid
      autoantibodies. The presence of any thyroid nodules with US and cytopathologic
      features was analyzed. The malignancy rate was also determined. RESULTS: Thyroid
      nodules were in 20 of the 89 patients (22.4%). Eight of these 20 patients (40%)
      had colloid cysts, two (10%) had nodular hyperplasia, one (5%) had follicular
      adenoma, and two (10%) had lymphocytic thyroiditis. Seven of the 89 patients
      (7.9%) were confirmed to have a malignancy, all of which were papillary thyroid
      carcinoma (PTC); of those, five patients had diffuse sclerosing variant PTC, and
      two had conventional PTC on pathology. CONCLUSION: The prevalence of thyroid
      nodules in children and adolescents with HT was 22.4%. The malignancy rate of
      children with HT was 7.9%. The malignancy rate among thyroid nodules was 35%,
      which is higher than the 26% rate generally reported for children with nodules.
      Therefore, using thyroid US to survey known or suspected thyroid nodules might be
      helpful in children and adolescents with HT and may provide further useful
      diagnostic information. Advances in knowledge: Thyroid US could help to assess HT
      patients who have known or suspected thyroid nodules.

PMID- 29595321
TI  - Influence of graded inclusion of white lupin (Lupinus albus) meal on performance,
      nutrient digestibility and ileal viscosity of laying hens.
AB  - 1. The aim of this study was to investigate the effect of white lupin (Lupinus
      albus) meal (WLM) addition on the intestinal viscosity, bird performance and
      nutrient utilisation of laying hens. 2. The experiment was conducted with 360
      laying hens aged 21 weeks fed one of 6 treatments, including a corn-soybean meal
      control diet (CON) and 5 experimental diets containing 60, 120, 180, 240 and 300
      g/kg WLM. 3. A linear increase in feed intake (p < 0.001) was observed with
      higher levels of WLM from 0 to 300 g/kg. Laying rate decreased quadratically (p <
      0.05) and egg weight (at 6th, 12th and 18th weeks of the trial) decreased
      linearly with WLM inclusion from 0 to 300 g/kg. Birds fed 60 g/kg or more of WLM
      laid lighter eggs (p < 0.05) than CON hens. When 240 g/kg or more WLM was
      included into the diet, laying rate was affected negatively (p < 0.05). 4. As WLM
      increased from 0 to 300 g/kg, apparent metabolisable energy and pre-caecal
      digestibility of dry matter and crude protein decreased quadratically (p < 0.05).
      When 300 g/kg of WLM was used, there was a tendency (p < 0.1) to decrease pre
      caecal starch digestibility. WLM dose exerted a quadratic effect (p < 0.05) on
      total sialic acid excretion. As WLM increased, the viscosity of ileal digesta
      linearly increased (p < 0.05). 5. In the 6th and 12th weeks of the experiment (p
      < 0.05), eggshell thickness decreased linearly when 240 g/kg of WLM was added. At
      the 6th, 12th and 18th weeks, a linear decrease in eggshell content was observed
      (p < 0.05) after WLM addition. 6. In conclusion, the graded inclusion of WLM into
      laying hens' diets resulted in depressed performance, AMEN and eggshell quality.

PMID- 29595322
TI  - Cone beam computed tomography virtual navigation-guided transthoracic biopsy of
      small (<= 1 cm) pulmonary nodules: impact of nodule visibility during real-time
      fluoroscopy.
AB  - OBJECTIVE: To evaluate the impact of nodule visibility during real-time
      fluoroscopy and other biopsy-related variables on the diagnostic accuracy and
      complication rates of cone beam CT (CBCT) virtual navigation (VN)-guided
      percutaneous transthoracic needle biopsies (PTNBs) of small (<=1 cm) pulmonary
      nodules. METHODS: Patients (99 males and 114 females; age, 62.1 +/- 11.1 years)
      who underwent CBCT VN-guided biopsies for lung nodules <= 1 cm were
      retrospectively reviewed. The visibility of target nodules was assessed on the
      captured fluoroscopy images. Diagnostic accuracies were calculated and logistic
      regression analyses were performed to determine independent influencing factors
      for the correct diagnosis and complications (pneumothoraxes and hemoptysis) in
      CBCT VN-guided PTNBs, respectively. RESULTS: Among 213 nodules, 63 (29.6%) were
      invisible on real-time fluoroscopy during VN. The diagnostic accuracy of CBCT VN
      guided PTNBs for the invisible nodules was 76.7%, while for the visible nodules
      was 89.1% (p = 0.042). In the logistic regression analysis, the visibility of a
      target nodule (odds ratio = 2.49, p = 0.047) was the only independent influencing
      factor for a correct diagnosis. As regards complication rates, nodule visibility
      was not a significant factor for the occurrence of a pneumothorax or hemoptysis.
      CONCLUSION: Although nodule visibility on real-time fluoroscopy was an affecting
      factor for the correct diagnosis, CBCT VN-guided PTNB was feasible for the
      invisible nodules with diagnostic accuracy of 76.7%. Advance in knowledge: CBCT
      VN-guided PTNB can be tried safely for the subcentimeter-sized pulmonary nodules
      regardless of their fluoroscopic visibility.

PMID- 29595323
TI  - CT and MR imaging characteristics of histological subtypes of head and neck
      ossifying fibroma.
AB  - OBJECTIVES: The current study aimed to assess CT and MRI characteristics of
      histological subtypes of head and neck ossifying fibroma (OF). METHODS: 12
      patients with histopathologically-proven head and neck OF were included in this
      study. Lesions were pathologically classified into three histological subtypes:
      eight cement-OFs (COFs), three juvenile psammomatoid OFs (JPOFs), and one
      juvenile trabecular OF (JTOF). All patients underwent CT examination, while seven
      also underwent MRI. Imaging characteristics were retrospectively assessed.
      RESULTS: On CT images, the lesion margins were well-defined in nine patients
      (75%) (seven COFs and two JPOFs), partially ill-defined in two (17%) (one COF and
      one JTOF), and ill-defined in one (8%) (one JPOF). The continuity of the eroded
      overlying bone cortex was maintained in nine patients (75%) (seven COFs and two
      JPOFs) but disrupted in three (25%) (one COF, one JPOF, one JTOF). With respect
      to lesion density, homogeneous ground-glass opacity was observed in five patients
      (42%) (five COFs), target-like appearance in three (25%) (two COFs, one JPOF),
      and mixture of hyper- and hypodense areas were observed in four (33%) (one COF,
      two JPOFs, one JTOF). MR signal intensity was homogeneous in two patients (29%)
      (two COFs) and heterogeneous in five (71%) (two COFs, two JPOFs, one JTOF).
      CONCLUSIONS: COFs tended to exhibit well-defined margins and preserved continuity
      of the overlying bone cortex. COFs were usually homogeneous, whereas JPOFs and
      JTOF were always heterogeneous. Target-like appearance was one of the
      characteristics of OFs, but it was observed in both COF and JPOF.

PMID- 29595324
TI  - Rhizome of Anemarrhena asphodeloides as mediators of the eco-friendly synthesis
      of silver and gold spherical, face-centred cubic nanocrystals and its anti
      migratory and cytotoxic potential in normal and cancer cell lines.
AB  - The water extract of Anemarrhena asphodeloides, the traditional oriental
      medicinal plant, mediated the eco-friendly synthesis of silver nanoparticles (Aa
      AgNPs) and gold nanoparticles (Aa-AuNPs). First, its therapeutic rhizome was
      powdered prior to water extraction and then silver, gold nanoparticles were
      synthesized. Aa-AgNPs and Aa-AuNPs were found to be spherical, face-centred cubic
      nanocrystals with a Z-average hydrodynamic diameter of 190 and 258 nm,
      respectively. In addition, proteins and aromatic biomolecules were the plausible
      players associated with the production and stabilization of Aa-AgNPs; instead,
      phenolic compounds were responsible for the synthesis and stability of Aa-AuNPs.
      In vitro cytotoxic analysis revealed that up to 50 MUg.mL-1 concentration Aa
      AuNPs did not exhibit any toxicity on 3T3-L1, HT29 and MCF7 cell lines, while
      being specifically cytotoxic to A549 cell line. On the contrary, Aa-AgNPs
      displayed a significantly higher toxicity in comparison to Aa-AuNPs in all cell
      lines specially MCF7 cell line. Since cancer cells were more sensitive to Aa
      Au/AgNPs treatments, further evaluation was done in order to determine their
      anticancer potential. Reactive oxygen species (ROS) generation was not affected
      by Aa-AuNPs, on the other hand, Aa-AgNPs treatment exhibited a higher potential
      to induce oxidative stress in A549 cells than HT29 and MCF7 cells. In addition,
      Aa-Ag/AuNPs reduced cell migration in A549 cells at 10 and 50 MUg.mL-1,
      respectively. So far, this is the only report uncovering the ability of A.
      asphodeloides to synthesize silver and gold nanoparticles with anticancer
      potential and also indirectly enabling its large-scale utilization with value
      addition.

PMID- 29595325
TI  - Cartilage can be thicker in advanced osteoarthritic knees: a tridimensional
      quantitative analysis of cartilage thickness at posterior aspect of femoral
      condyles.
AB  - OBJECTIVE: To test, through tridimensional analysis, whether (1) cartilage
      thickness at the posterior aspect of femoral condyles differs in knees with
      medial femorotibial osteoarthritis (OA) compared to non-OA knees; (2) the
      location of the thickest cartilage at the posterior aspect of femoral condyles
      differs between OA and non-OA knees. METHODS: CT arthrograms of knees without
      radiographic OA (n = 30) and with severe medial femorotibial OA (n = 30) were
      selected retrospectively from patients over 50 years of age. The groups did not
      differ in gender, age and femoral size. CT arthrograms were segmented to measure
      the mean cartilage thickness, the maximal cartilage thickness and its location in
      a region of interest at the posterior aspect of condyles. RESULTS: For the medial
      condyle, mean and maximum cartilage thicknesses were statistically significantly
      higher in OA knees compared to non-OA knees [1.66 vs 1.46 mm (p = 0.03) and 2.56
      vs 2.14 mm (p = 0.003), respectively]. The thickest cartilage was located in the
      half most medial aspect of the posterior medial condyle for both groups, without
      significant difference between groups. For the lateral condyle, no statistically
      significant difference between non-OA and OA knees was found (p >= 0.17).
      CONCLUSION: Cartilage at the posterior aspect of the medial condyle, but not the
      lateral condyle, is statistically significantly thicker in advanced medial
      femorotibial OA knees compared to non-OA knees. The thickest cartilage was
      located in the half most medial aspect of the posterior medial condyle. These
      results will serve as the basis for future research to determine the
      histobiological processes involved in this thicker cartilage. Advances in
      knowledge: This study, through a quantitative tridimensional approach, shows that
      cartilage at the posterior aspect of the medial condyles is thicker in severe
      femorotibial osteoarthritic knees compared to non-OA knees. In the posterior
      aspect of the medial condyle, the thickest cartilage is located in the vicinity
      of the center of the half most medial aspect of the posterior medial condyle.
      These results will serve as the basis for future research to determine the
      histobiological processes involved in this thicker cartilage.

PMID- 29595326
TI  - A real-world analysis of glycemic control among patients with type 2 diabetes
      treated with canagliflozin versus dapagliflozin.
AB  - OBJECTIVE: This US retrospective cohort study compared the real-world
      effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg on HbA1c
      reduction in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients
      initiated on canagliflozin 300 mg or dapagliflozin 10 mg were identified from de
      identified claims data in the Optum Clinformatics database (1 January 2014-30
      September 2016). Propensity score matching was used to create balanced cohorts.
      The primary outcome was the proportion of patients with HbA1c <8.0% (HEDIS
      target); secondary outcomes included the proportion of patients with HbA1c <7.0%
      (ADA target) and >9.0% (HEDIS poor control), absolute change in HbA1c, and
      treatment patterns. RESULTS: At 6 months post-index (intent-to-treat population),
      a significantly higher proportion of patients in the canagliflozin 300 mg versus
      dapagliflozin 10 mg cohort achieved HbA1c <8.0% (70.8% vs. 59.1%; OR [95% CI]:
      1.60 [1.26, 2.04]; p = .0001) and HbA1c <7.0% (36.7% vs. 25.1%; OR [95% CI]: 1.75
      [1.34, 2.27]; p < .0001). A similar proportion of patients had HbA1c >9.0%. Mean
      HbA1c reduction was -1.17% with canagliflozin 300 mg and -0.91% with
      dapagliflozin 10 mg (difference of -0.26%; p = .0049). HbA1c results from a
      sensitivity analysis in the on-treatment population were consistent with the
      primary analysis. Patients in the canagliflozin 300 mg versus dapagliflozin 10 mg
      cohort were less likely to discontinue treatment (OR [95% CI]: 0.75 [0.57, 0.99];
      p = .0400) or switch medication (OR [95% CI]: 0.72 [0.54, 0.96]; p = .0229).
      CONCLUSIONS: In this real-world study, patients with T2DM initiated on
      canagliflozin 300 mg had better HbA1c goal attainment and larger HbA1c reduction
      than patients initiated on dapagliflozin 10 mg.

PMID- 29595327
TI  - The antioxidant system in the soleus muscle of growing rats is stimulated by the
      administration of a low-protein/high-carbohydrate diet.
AB  - The aim of this study was to evaluate the generation of reactive oxygen species
      (ROS) by xanthine oxidase (XO), the enzymatic antioxidant system and oxidative
      damage in soleus and extensor digitorum longus (EDL) muscles of growing rats fed
      a low-protein, high-carbohydrate (LPHC; 6% protein, 74% carbohydrate) diet for 15
      days. The LPHC diet increased the total antioxidant capacity by 45% and the
      activities of glutathione peroxidase (GPx), glutathione reductase and catalase in
      the soleus muscles. There was an increase in the carbonylated proteins with no
      increase thiobarbituric acid reactive substances (TBARS), although the XO
      activity had increased 20%. In EDL muscles, the LPHC diet increased XO activity
      by 66% and the TBARS levels by 80%, and only GPx had its activity increased.
      These results suggest that the enzymatic antioxidant system of the soleus muscle
      has a better response to the increase of ROS production stimulated by LPHC diet.

PMID- 29595328
TI  - Bt354 as a new STAT3 signaling pathway inhibitor against triple negative breast
      cancer.
AB  - Inhibition of the signal transducer and activator of transcription 3 (STAT3)
      signalling pathway has been considered as a novel therapeutic strategy to treat
      human cancers with constitutively active STAT3. In this study, we screened 1563
      compounds and identified Bt354 as a new small-molecule inhibitor of the STAT3
      signalling pathway. The effect of Bt354 on STAT3 activity was initially screened
      and Bt354 significantly inhibited STAT3 activity in a dual luciferase assay.
      Bt354 inhibited the proliferation of cancer cells in a dose- and time-dependent
      manner. The phosphorylation of STAT3 at Y705 was suppressed without affecting the
      phosphorylation of STAT3 at S727 in breast cancer cells. Furthermore, Bt354
      inhibited the nuclear translocation of STAT3 and consequently induced cell growth
      inhibition, apoptosis and cell cycle G2/M arrest in triple negative breast cancer
      cells. In vivo, Bt354 also inhibited tumour growth in MDA-MB-435 and MDA-MB-231
      xenograft mice without affecting body weight. Computational modelling showed that
      Bt354 could bind to the SH2 domain of STAT3. These findings suggest that Bt354
      may be a potent anticancer agent for STAT3-activated triple negative breast
      cancer cells.

PMID- 29595329
TI  - Sacubitril and valsartan protect from experimental myocardial infarction by
      ameliorating oxidative damage in Wistar rats.
AB  - BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of
      neprilysin and activate cGMP signaling pathways leading to rise in blood volume
      concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and
      bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic
      effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced
      myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected
      subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL).
      RESULT: Biochemical investigation revealed that SAC along with VAL significantly
      prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH)
      degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats.
      Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also
      significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently,
      decreased infarction area (IA)and marked reduction in myofibril damage by SACand
      VAL further supported its protective benefits in MI. CONCLUSION: Taken together,
      the results suggest that inhibition of enzyme neprilysin alleviated the ISO
      induces myocardial damage mediated by its strong antioxidant potential.

PMID- 29595330
TI  - Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC)
      Inhibitor, in Ischemia Reperfusion in Mouse Eyes.
AB  - PURPOSE: The purpose of the current study is to assess changes in the expression
      of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs)
      after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of
      ASIC1a provides RGC neuroprotection. METHODS: Transient ischemia was induced in
      one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min
      followed by retinal reperfusion by restoring normal pressure. RGC function was
      measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and
      ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain,
      fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1),
      catalase, and glutathione perioxidase-4 (GPX4) protein levels were assessed by
      western blot. RGC numbers were measured by immunohistochemistry on whole retinal
      flat mounts using anti-RNA binding protein with multiple splicing (RBPMS)
      antibodies. Intravitreal injection of psalmotoxin-1, a selective ASIC1a blocker,
      was used to assess the neuroprotective effect of ASIC1a inhibition. RESULTS:
      Levels of ASIC1a and ASIC2 after I/R increased in RGCs. Upregulation of ASIC1a
      but not ASIC2 was attenuated by intravitreal injection of psalmotoxin-1. I/R
      induced activation of calpain and degradation of fodrin, HSP70, and reduction in
      Brn3a. In contrast, while psalmotoxin-1 attenuated calpain activation and
      increased Brn3a levels, it failed to block HSP70 degradation. Unlike SOD1 protein
      which was reduced, catalase protein levels increased after I/R. Psalmotoxin-1,
      although not affecting SOD1 and GPX4, increased catalase levels significantly.
      Psalmotoxin-1 also increased RBPMS-labeled RGCs following I/R as judged by
      immunohistochemistry of retinal flat mounts. Finally, psalmotoxin-1 enhanced the
      amplitude of PERG following I/R, suggesting partial rescue of RGC function.
      CONCLUSION: Psalmotoxin-1 appears to exert a neuroprotective effect under
      ischemic insults and targeting inhibition of ASICs may represent a new
      therapeutic approach in ischemic retinal diseases.

PMID- 29595331
TI  - Vegetarianism, depression, and the five factor model of personality.
AB  - This study investigated whether vegetarians and omnivores differ in their
      personality characteristics. We measured the five factor model of personality and
      depressive symptoms in vegetarians, who avoided meat and fish (n = 276); semi
      vegetarians, who ate some meat and/or fish (n = 1191); and omnivores (n = 4955).
      Although vegetarians and semi-vegetarians were more open to new experiences, they
      were more neurotic and depressed than omnivores. Neither conscientiousness nor
      agreeableness varied as a function of dietary habits. These findings contribute
      to our understanding about differences between vegetarians' and omnivores'
      personalities, which might help us better understand individual differences in
      food preferences.

PMID- 29595332
TI  - Three-dimensional CBCT images registration method for TMJ based on reconstructed
      condyle and skull base.
AB  - OBJECTIVES: A method was introduced for three-dimensional (3D) cone-beamCT (CBCT)
      images registration of temporomandibular joint (TMJ). This study aimed to provide
      quantitative and qualitative analysis of TMJ bone changes in two-dimensional (2D)
      and 3D and to provide the technique for computer-aided diagnosis of
      temporomandibular joint disorders in the future. METHODS: 10 TMJ samples of six
      patients were obtained from Peking University Hospital of Stomatology. Four of
      the six patients imaged bilateral TMJs and the other two patients only imaged
      unilateral TMJ. Each sample consisted of two images from the same TMJ taken at
      different times. First, condyle and skull base were segmented semi-automatically
      for 3D model reconstruction. Then the segmented condyle and skull base were
      registered separately. Registration process can be divided into two processes of
      rough registration and fine registration. Rough registration step was achieved by
      selecting corresponding points manually and initialized fine registration.
      Condyle and skull base were fine registered by minimizing mean square error of
      condyle (MSEcondyle) and skull base (MSEskull) respectively. Qualitative
      assessment of osseous component changes utilized 2D color-fused model and 3D
      surface-fused model and quantitative analyses the convergence of this method used
      the mean square error of the model (MSEmodel). Independent repeated experiments
      were carried out to test the stability of our 3D registration method. RESULTS:
      Sufficiently alignment was achieved. Osseous abnormality and morphology changes
      were displayed using fusion model. MSEmodel of condylar registration and skull
      base registration declined 51.80% and 64.58% compared with that before
      registration. Quantitative analysis verified the stability of the method.
      CONCLUSIONS: The proposed method completed 3D TMJ registration for different
      physiological structure. The result of this method was accurate, reproducible and
      not relied on the experience of operators.

PMID- 29595333
TI  - Computer vision analysis captures atypical attention in toddlers with autism.
AB  - To demonstrate the capability of computer vision analysis to detect atypical
      orienting and attention behaviors in toddlers with autism spectrum disorder. One
      hundered and four toddlers of 16-31 months old (mean = 22) participated in this
      study. Twenty-two of the toddlers had autism spectrum disorder and 82 had typical
      development or developmental delay. Toddlers watched video stimuli on a tablet
      while the built-in camera recorded their head movement. Computer vision analysis
      measured participants' attention and orienting in response to name calls.
      Reliability of the computer vision analysis algorithm was tested against a human
      rater. Differences in behavior were analyzed between the autism spectrum disorder
      group and the comparison group. Reliability between computer vision analysis and
      human coding for orienting to name was excellent (intra-class coefficient 0.84,
      95% confidence interval 0.67-0.91). Only 8% of toddlers with autism spectrum
      disorder oriented to name calling on >1 trial, compared to 63% of toddlers in the
      comparison group (p = 0.002). Mean latency to orient was significantly longer for
      toddlers with autism spectrum disorder (2.02 vs 1.06 s, p = 0.04). Sensitivity
      for autism spectrum disorder of atypical orienting was 96% and specificity was
      38%. Older toddlers with autism spectrum disorder showed less attention to the
      videos overall (p = 0.03). Automated coding offers a reliable, quantitative
      method for detecting atypical social orienting and reduced sustained attention in
      toddlers with autism spectrum disorder.

PMID- 29595334
TI  - Concordance between physiological arousal and emotion expression during fear in
      young children with autism spectrum disorders.
AB  - This study aimed to measure emotional expression and physiological arousal in
      response to fear in 21 children with autism spectrum disorders (43-75 months) and
      45 typically developing children (41-81 months). Expressions of facial and bodily
      fear and heart rate arousal were simultaneously measured in response to a remote
      controlled robot (Laboratory Temperament Assessment Battery). Heart rate analyses
      revealed a main effect of task from baseline to fear ( p < 0.001, [Formula: see
      text]), no interaction effect and no effect for group. In addition, children with
      autism spectrum disorder showed intact facial and bodily expressions of fearful
      affect compared to typically developing children. With regard to the relationship
      between expression and arousal, the results provided evidence for concordance
      between expression and arousal in typically developing children ( r = 0.45, n =
      45, p < 0.01). For children with autism spectrum disorder, no significant
      correlation was found ( r = 0.20, n = 21, p = 0.38). A moderation analysis
      revealed no significant interaction between expression and arousal for children
      with and without autism spectrum disorder ( F(1, 62) = 1.23, p = 0.27, [Formula:
      see text]), which might be the result of limited power. The current results give
      reason to further study concordance between expression and arousal in early
      autism spectrum disorder. Discordance might significantly impact social
      functioning and is an important topic in light of both early identification and
      treatment.

PMID- 29595335
TI  - Functional changes during visuo-spatial working memory in autism spectrum
      disorder: 2-year longitudinal functional magnetic resonance imaging study.
AB  - This study examined functional changes longitudinally over 2 years in neural
      correlates associated with working memory in youth with and without autism
      spectrum disorder, and the impact of increasing cognitive load. We used
      functional magnetic resonance imaging and a visuo-spatial 1-back task with four
      levels of difficulty. A total of 14 children with autism spectrum disorder and 15
      typically developing children (ages 7-13) were included at baseline and followed
      up approximately 2 years later. Despite similar task performance between groups,
      differences were evident in the developmental trajectories of neural responses.
      Typically developing children showed greater load-dependent activation which
      intensified over time in the frontal, parietal and occipital lobes and the right
      fusiform gyrus, compared to those with autism spectrum disorder. Children with
      autism spectrum disorder showed minimal age-related changes in load-dependent
      activation, but greater longitudinal load-dependent deactivation in default mode
      network compared to typically developing children. Results suggest inadequate
      modulation of neural activity with increasing cognitive demands in children with
      autism spectrum disorder, which does not mature into adolescence, unlike their
      typically developing peers. Diminished ability for children with autism spectrum
      disorder to modulate neural activity during this period of maturation suggests
      that they may be more vulnerable to the increasing complexity of social and
      academic demands as they progress through adolescence than their peers.

PMID- 29595336
TI  - Scoping the evidence for EarlyBird and EarlyBird Plus, two United Kingdom
      developed parent education training programmes for autism spectrum disorder.
AB  - EarlyBird and EarlyBird Plus are parent education and training programmes
      designed by the UK National Autistic Society in 1997 and 2003, having been
      delivered to more than 27,000 families in 14 countries. These group-based
      programmes aim to (1) support parents immediately after diagnosis of autism
      spectrum disorder, (2) empower parents, encouraging a positive perception of
      their child's autism spectrum disorder and (3) help parents establish good
      practice. In the absence of any previous comprehensive review, we performed a
      scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A
      search was conducted between February and June 2016 using EbscoHost, Sabinet,
      SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus,
      ScienceDirect and grey literature. Two reviewers independently screened titles
      and abstracts for inclusion. In total, 18 articles were identified: 16 from the
      United Kingdom and 2 from New Zealand. We reviewed the context, study
      populations, design, outcome measures, whether focus was on parental perception,
      parental change or child changes and programme feasibility. Strong parental
      support for the acceptability but lower level evidence of efficacy of
      EarlyBird/EarlyBird Plus was found. Future research should consider randomised
      controlled trials. There is no research on EarlyBird/EarlyBird Plus in low
      resource settings; therefore, we recommend broader feasibility evaluation of
      EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and
      scalability.

PMID- 29595338
TI  - Multifunctional fluorescent titania nanoparticles: green preparation and
      applications as antibacterial and cancer theranostic agents.
AB  - Theranostic nanoparticles have attracted considerable attention in recently
      revolutionized medicine. Since the last decade, there has been a growing attempt
      to design various theranostic nanoparticles but difficulties still exist in the
      fabrication of their biocompatible one. Herein, fluorescent titania nanoparticles
      (FTN) were fabricated using a one-step green method. This FTN had ultra-high
      doxorubicin hydrochloride (DOX) loading capacity (encapsulation efficiency 95.50%
      and loading content 38.20%) that release the loaded drug in response to acidic
      pH. In vitro cytotoxicity experiments on human osteosarcoma (SaOs-2) and breast
      cancer (MCF-7) cell lines revealed superior anticancer efficacy (lowered the IC50
      concentration by 3- and 5.5-fold for SaOs-2 and MCF-7 cells, respectively) and
      also better imaging for intracellular tracking of DOX/FTN relative to free DOX.
      Furthermore, the prepared nanoparticles showed efficient antibacterial activity
      against both gram-negative (Escherichia coli ATCC 25922) and gram-positive
      (Staphylococcus aureus ATCC 25923) bacteria. In this study, we have developed
      novel theranostic titania nanoparticles with inherent fluorescence property for
      cancer imaging and therapy.

PMID- 29595337
TI  - Mitochondria-homing peptide functionalized nanoparticles performing dual
      extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity.
AB  - One of the major challenges in the treatment of hearing loss is the low efficacy
      of therapeutic candidates. To achieve the optimum drug efficacy, we designed a
      novel peptide (D-Arg-Dmt-Arg-Phe-NH2)-mediated mitochondrial targeted delivery
      nanosystem for a promising candidate, geranylgeranylacetone (GGA). The zebrafish
      lateral line system, a robust model for mammalian hair cells, was used to
      identify the efficacy against gentamicin, a well-known ototoxic agent. The
      nanosystem facilitated lysosomal escape and mitochondrial accumulation, and thus
      conferred superior protective efficacy against a wide range of gentamicin
      compared with unmodified NPs and free drugs. Meanwhile, peptides-modified NPs
      internalized hair cells via both of dynamin-dependent and independent routes,
      following a classic endocytic or autophagy pathway. Although extracellular action
      via MET channels, the primary protective mechanism underlying peptides-modified
      NPs was revealed due to their intracellular interaction. Thus, our nanoplatform
      provided a general strategy to enhance the clinical efficacy of a broad range of
      drugs in the treatment of hearing loss.

PMID- 29595339
TI  - Antifeedant activity of long-chain alcohols, and fungal and plant metabolites
      against pea aphid (Acyrthosiphon pisum) as potential biocontrol strategy.
AB  - Aphids are noxious insect pests of major crops including cereals and legumes.
      Particularly, pea aphid (Acyrthosiphon pisum) causes significant yield and
      quality loses in pea. Crop protection is largely based on noxious chemical
      pesticides which have prompted a renewed interest in the discovery of natural
      products as alternatives to synthetic insecticides. In this study different
      classes of natural compounds were tested in dual choice bioassays to evaluate
      their feeding deterrence and mortality effect on pea aphid. High feeding
      deterrence was produced by some of the compounds, particularly1-hexadecanol,
      gliotoxin, cyclopaldic acid and seiridin. On the contrary, aphid mortality was
      low although significant for 1-heptadecanol, cytochalasin A, 1-nonadecanol and
      gliotoxin. Phytotoxicity assessment showed low or imperceptible plant damaged for
      cytochalasin A, seiridin and 1-nonadecanol. The results obtained showed the
      potential of seiridin to be used as an alternative to synthetic insecticides.

PMID- 29595341
TI  - Beneficial Effects of ragi (Finger Millet) on Hematological Parameters, Body Mass
      Index, and Scholastic Performance among Anemic Adolescent High-School Girls
      (AHSG).
AB  - Adolescence is a period characterized by rapid physical, emotional, and mental
      growth and changes potentially resulting in health challenges. Anemia, which is a
      fairly common complication in this age group, is reported to negatively affect
      the cognitive ability of adolescents. Traditionally, ragi (Finger millet:
      Eleusine coracana), a cereal available in India, has been recommended as
      nutritional supplement to combat anemia because of its high protein and mineral
      content as well as anti-microbial property. This study sought to establish the
      effect of ragi in improving hematological parameters, body mass index, and
      scholastic performance among adolescent school girls. Sixty adolescent girls were
      randomly selected and divided into intervention (n = 30) and control groups (n =
      30). The effect of dietary supplementation of ragi porridge on hematological
      parameters was evaluated on the intervention group at 45 and 90 days. Both groups
      were monitored for changes in body mass index and scholastic performance. A
      statistically significant increase in hemoglobin levels was observed in the
      intervention group after 90 days (from a mean of 11.3 g% to 12.54 g%; t (29) =
      7.514, p < .0001), with no significant changes in the control group. No
      statistically significant differences between the two groups were observed for
      mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean
      corpuscular volume, red cell distribution width, body mass index, and scholastic
      performance. The data show that daily dietary supplementation with ragi porridge
      has a positive effect on hemoglobin levels in adolescent high schools girls. A
      well planned nutrition education with dietary supplementation is thus recommended
      for better outcomes.

PMID- 29595340
TI  - Correlation of ST changes in leads V4-V6 to area of ischemia by CMR in inferior
      STEMI.
AB  - OBJECTIVE: We aim to determine the correlation between ST-segment changes in
      leads V4-V6 and the extent of myocardial injury by cardiac magnetic resonance
      (CMR) in patients with inferior ST elevation (STE) myocardial infarction
      (iSTEMI). DESIGN: Admission electrocardiogram and CMR data from the MITOCARE
      trial were used. Differences in mean myocardium at risk, infarct size, ejection
      fraction and myocardial segment involvement by CMR were compared in patients with
      first iSTEMI with STE, ST depression (STD) or no ST changes (NST) in V4-V6.
      Myocardial segment involvement was further evaluated by comparing proportion of
      patients in each group with >=25% and >=50% segment involvement. RESULTS: Fifty
      four patients were included. Patients with STE (n = 22) and STD (n = 16) in V4-V6
      had significantly lower ejection fraction compared to NST (n = 16) (48% vs 48% vs
      54%, p = .02). STE showed more apical, apical lateral and mid-inferolateral
      involvement but less basal inferior involvement than NST. STD exhibited greater
      basal inferoseptal involvement compared to STE. There were more patients with STE
      that had >=25% and >=50% apical lateral involvement compared with STD and NST
      groups. Patients with STD were more likely to have >=25% and >=50% basal
      inferoseptal involvement compared with STE and NST groups. CONCLUSION: Our study
      suggests that in iSTEMI, ST changes in the precordial leads V4-V6 correlates with
      greater myocardial injury and distribution of myocardium at risk.

PMID- 29595342
TI  - Lifetime alcohol intake and pattern of alcohol consumption in patients with
      alcohol-induced pancreatitis in comparison with patients with alcohol use
      disorder.
AB  - OBJECTIVE: To examine lifetime drinking patterns in men and women with alcohol
      induced pancreatitis (AIP) in comparison with patients with alcoholic use
      disorder (AUD) without pancreatic disease. METHODS: Alcohol consumption patterns
      were assessed using a validated questionnaire, the Lifetime Drinking History
      (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for
      gender and age (+/- 5 years) with patients with AUD in addiction treatment.
      RESULTS: A total of 45 patients with AIP (35 males, 10 females) and 45 AUD
      patients were included. Alcohol consumption patterns were not significantly
      different between males and females with AIP and those with history of acute AIP
      and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD
      patients were similar in terms of onset age and duration of alcohol consumption,
      lifetime alcohol intake and drinks per drinking day. A higher proportion of binge
      drinking was found among patients with AUD than those with AIP (median 1.00 vs.
      0.94, p = .01). Males with AUD had lower onset age (15 vs. 16 years, p = .03),
      higher total amount of spirits (35520 vs. 10450 drinks, p = .04) and higher
      proportion of binge drinking (1.00 vs. 0.97, p = .01) than males with AIP,
      whereas females with AIP and AUD had similar drinking patterns. CONCLUSIONS:
      Alcohol drinking patterns and lifetime drinking history was similar in patients
      with AIP and patients with AUD. Males with AIP had lower total amount of spirits
      and lower proportion of binge drinking than those with AUD, suggesting the
      idiosyncratic etiology of AIP.

PMID- 29595343
TI  - On the persistence and detectability of ancient Beothuk mitochondrial DNA genomes
      in living First Nations peoples.
AB  - Claims have long been made as to the survival to the present day of descendants
      of the Newfoundland Beothuk, a group generally accepted to have become extinct
      with the death of the last known member, Shanawdithit, in 1829. Interest has
      recently been revived by the availability of commercial genetic testing, which
      some claim can assign living individuals to specific Native American groups. We
      compare complete mitogenome sequences (16569 bp) from aDNA of eight distinct
      Beothuk lineages, including Shanawdithit's uncle Nonosabasut and his wife
      Demasduit, with three Newfoundland Mi'kmaq lineages and 21 other living Native
      Americans drawn from GenBank. A Newfoundland Mi'kmaq lineage in Haplogroup A is
      more similar to three Native Americans (1-3 SNPs) than to the most closely
      related Beothuk (24 SNPs). Nonosabasut in Haplogroup X is identical to a non
      Beothuk Native American. Demasduit in Haplogroup C differs from three other
      Native Americans by 1-4 substitutions. Within a 2168 bp region of the HVS
      sequences available from living Mi'kmaq of the Miawpukek First Nation in
      Newfoundland, lineages in Haplogroups C, X, and A differ by 1, 4, and 8
      substitutions, from the most similar Beothuk, and are more similar to other
      Native Americans. MtDNA genome sequences in living persons identical or similar
      to those of Beothuk do not necessarily indicate Beothuk ancestry. Mi'kmaq
      lineages cannot at this time be associated with any Beothuk lineages more closely
      than those of other Native Americans.

PMID- 29595344
TI  - Seroepidemiology and phylogenetic analysis of human herpesvirus type 8 in
      injection drug users and men who have sex with men in northern Taiwan.
AB  - Objectives Human herpesvirus 8 (HHV-8) is transmissible and causes Kaposi's
      sarcoma and other malignancies. This study analyzed the seroepidemiology and
      phylogeny of HHV-8 among 515 injection drug users (IDUs) and 229 men who have sex
      with men (MSM) in Taiwan. Methods Blood and peripheral mononuclear cells were
      analyzed for HHV-8 seroprevalence using enzyme-linked immunosorbent and
      immunofluorescence assays. Viral loads were measured using a real-time PCR assay.
      Phylogenetic analysis of the K1 gene was performed using nested PCR and DNA
      sequencing. Results HHV-8 infection rate was higher in MSM (24.9%) than in IDUs
      (3.8%). The rate of HHV-8 infection was higher in HIV-1-positive patients (32.8%,
      MSM; 5.5%, IDUs) than in HIV-1 negative patients. HHV-8 load was not
      significantly different between HHV-8 seropositive and seronegative patients. HHV
      8 genotypes C and A variants were detected at frequencies of 80% and 20%,
      respectively, among IDUs; and genotypes C, D, E, and A were detected at
      frequencies of 55.6%, 11.1%, 11.1%, and 5.6%, respectively, among MSM. Variants
      of K1 amino acid residues 54-84 were detected in most IDUs and MSM. Conclusions
      HHV-8 prevalence was significantly higher among MSM than among IDUs. Evolution of
      the K1 gene occurred in HHV-8 variants of IDUs and MSM.

PMID- 29595345
TI  - Respira project: Humanistic and economic burden of asthma in Brazil.
AB  - OBJECTIVE: To determine the association of asthma on health-related quality of
      life (QoL), productivity, and use of healthcare resources among adults in Brazil.
      METHODS: Data were analyzed from the 2015 Brazil National Health and Wellness
      Survey, a cross-sectional survey with 12,000 adult respondents. Asthma and
      control groups were compared with respect to health-related QoL, asthma control,
      work productivity, and adherence. Generalized linear models were developed to
      compare asthma-related associations controlling for potential confounding
      factors. RESULTS: Among respondents, 4.1% (n = 494) reported an asthma diagnosis;
      those without asthma symptoms were used as the control group (n = 11,487).
      Regarding asthma control, 51.2% of patients had uncontrolled asthma, 36.4%
      partially controlled asthma, and 12.3% were fully controlled. Short-acting beta2
      agonists were the most commonly used class of drugs (38.5%). Approximately 32.4%
      of asthma patients were considered fully adherent to their treatment. In
      multivariable analyses, asthma patients presented lower health-related QoL and
      had more frequent visits with medical healthcare providers (6.1 versus 4.2)
      emergency room visits (1.0 versus 0.5), and more hospitalizations (0.4 versus
      0.2), than control respondents six months prior to the study (p < 0.05). Rates of
      absenteeism and presenteeism varied between 11.5% and 7.4% (p < 0.05) and 30.4%
      and 20.9% (p < 0.001) between asthma patients and controls, respectively.
      CONCLUSIONS: Asthma had a negative association on health-related QoL, work
      productivity, and use of healthcare resources. Excessive use of short-acting
      beta2 agonists and poor treatment adherence reflect poor asthma control and
      suggest the need to implement new strategies for asthma treatment in Brazil.

PMID- 29595346
TI  - A proteomic approach reveals the variation in human platelet protein composition
      after storage at different temperatures.
AB  - Cryopreservation can slow down the metabolism and decrease the risk of bacterial
      contamination. But, chilled platelets (PLTs) show a reduced period in circulation
      due to the rapid clearance by hepatic cells or spleen macrophages after
      transfusion. The deleterious changes that PLTs undergo are mainly considered the
      result of PLT protein variation. However, the basis for proteomic variation of
      stored PLTs remains poorly understood. Besides count, activation markers (CD62P
      and Annexin V), and aggregation, we used quantitative mass spectrometry to create
      the first comprehensive and quantitative human PLT proteome of samples stored at
      different temperatures (22 degrees C, 10 degrees C and -80 degrees C). We found
      different conditions caused different platelet storage lesion (PSL). PLT count
      was decreased no matter at what temperature stored. PLTs viability at low
      temperature dropped by 21.78% and 11.21%, respectively, as compared 10.26% at
      room temperature, there were no significant differences between the storage
      methods. Membrane expression of CD62P gradually increased in all groups
      especially stored at 22 degrees C up to 40% and 10 degrees C up to 30%. However,
      exposure of PS on the PLT membrane was below 1% in every group. The PLT proteome
      showed there were 575 and 454 potential proteins identified by general iTRAQ
      analysis and phosphorylation iTRAQ a nalysis, respectively, among them, 33 common
      differentially expressed proteins caused by storage time and 44 caused by storage
      temperature Especially, membrane-bound proteins (such as FERMT3, STX4, MYL9 and
      TAGLN2) played key roles in PLT storage lesion. The pathways "Endocytosis", "Fc
      gamma R-mediated phagocytosis" and "Regulation of actin cytoskeleton" were
      affected predominantly by storage time. And the pathways "SNARE interactions in
      vesicular transport" and "Vasopressin-regulated water reabsorption" were affected
      by cold storage in our study. Proteomic results can help us to understand PLT
      biochemistry and physiology and thus unravel the mechanisms of PSL in time and
      space for more successful PLT transfusion therapy.

PMID- 29595347
TI  - Relationship between human immunodeficiency virus (HIV-1) infection and chronic
      periodontitis.
AB  - INTRODUCTION: Current studies show that, even in the era of antiretroviral
      therapies, HIV-1 infection is associated with more severe and frequent refractory
      chronic periodontitis. Areas covered: This review, based on a systematic analysis
      of the literature, intends to provide an update on factors that may be involved
      in the pathogenesis of periodontal disease in HIV-1-infected patients, including
      local immunosuppression, oral microbial factors, systemic inflammation, salivary
      markers, and the role of gingival tissue as a possible reservoir of HIV-1. Expert
      commentary: The therapeutic revolution of ART made HIV-1 infection a chronic
      controllable disease, reduced HIV-1 mortality rate, restored at least partially
      the immune response and dramatically increased life expectancy of HIV-1-infected
      patients. Despite all these positive aspects, chronic periodontitis assumes an
      important role in the HIV-1 infection status for activating systemic inflammation
      favoring viral replication and influencing HIV-1 status, and also acting as a
      possible reservoir of HIV-1. All these issues still need to be clarified and
      validated, but have important clinical implications that certainly will benefit
      the diagnosis and management of chronic periodontitis in HIV-1-infected patients,
      and also contributes to HIV-1 eradication.

PMID- 29595349
TI  - Rebuttal from Saltin and Calbet.

PMID- 29595348
TI  - PARP inhibitors for homologous recombination-deficient prostate cancer.
AB  - INTRODUCTION: Prostate adenocarcinoma represents a leading cause of cancer
      related mortality. Increased emphasis on understanding the molecular basis of
      prostate cancer has identified a substantial burden of homologous recombination
      (HR) pathway mutations, which are enriched in castrate-resistant disease. This
      discovery has yielded novel therapeutic opportunities. Areas covered: We will
      discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus
      on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space.
      Evidence for use in HR-deficient patients will be outlined with discussion of the
      mechanism of action for this drug class, pathways of resistance, and approaches
      for expanding PARP inhibitor use to non-HR-deficient prostate cancer subgroups.
      Expert opinion: PARP inhibition represents an exciting tool for management of HR
      inactivated CRPC. With rapid adoption of next-generation sequencing technologies
      and other molecular techniques, the number of patients in this category is likely
      to increase. Ongoing and future investigations will be critical for improved
      understanding of the promise and appropriate treatment sequencing of PARP
      inhibition and optimal options for HR-proficient and -deficient prostate cancer
      populations. Questions remain about the clinical significance of monoallelic vs.
      biallelic HR mutations, the relevance of germline vs. somatic-only mutations, and
      the importance of mutations in non-canonical HR genes.

PMID- 29595350
TI  - Factors influencing the level of self-stigmatisation in people with mental
      illness.
AB  - AIM: The aim of this study was to assess sociodemographic factors and factors
      connected with treatment of mental illness and to decide whether they can
      influence the level of self-stigma. METHOD: Sociodemographic characteristics
      (age, gender, family status, level of employment, level of education) and
      characteristics related to illness and treatment (diagnosis, length of treatment,
      adherence to treatment) were gathered in a group of patients in stable mental
      condition, without acute symptoms of mental illness. Self-stigma was measured
      using the Self-stigma of Mental Illness Scale - short form (SSMIS-SF). RESULTS:
      The sample included 197 patients: 99 patients in group 1 (G1) with psychosis and
      98 in group 2 (G2) with anxious and affective disorders. The average age was
      44.15 +/- 12.91 years, the length of illness was 11.67 +/- 9.21 years and 48% of
      patients were men. The total average SSMIS-SF score was 61.54 +/- 23.34. We found
      no statistically significant difference in the total level of self-stigmatisation
      between these groups ( t(197) = 0.77; p = .441). The level of self-stigmatisation
      (total score of SSMIS-SF) in patients in G1 (psychosis) increased with the length
      of illness r(99) = .253; p = .011. Employment status seems to correlate with the
      level of self-stigmatisation ( F(3, 184) = 5.27; p = .002). Patients unemployed
      and on disability pension had higher levels of self-stigmatisation than patients
      working full-time. Patients who took medication regularly (full medical
      adherence) had lower scores of SSMIS-SF total scores in comparison with patients
      with lower compliance ( t(195) = 3.476; p = .001; Cohen's d = .25). CONCLUSION:
      According to our results, with regard to the factors that were followed, self
      stigmatisation correlates with the presence of employment (social inclusion),
      duration of illness in patients with psychosis and treatment adherence. We did
      not find a statistically significant influence of age, gender, marital status or
      clinical diagnosis on the level of self-stigma.

PMID- 29595351
TI  - Treatment and prevention of HIV infection with long-acting antiretrovirals.
AB  - INTRODUCTION: Current antiretroviral therapy allows to achieve and sustain
      maximal suppression of HIV replication in most treated patients. As result, the
      life expectancy of HIV-infected persons has improved dramatically and is nowadays
      similar to that of the HIV-negative population. However, oral antiretrovirals
      have to be taken daily and indefinitely to avoid resumption of HIV replication
      and selection of drug resistance. Unfortunately, drug adherence is often
      suboptimal and tends to decline over time. Areas covered: New drugs, formulations
      and delivery systems are being developed for extended-release of antiretrovirals.
      At this time, intramuscular cabotegravir and rilpivirine, dapivirine vaginal
      rings and tenofovir alafenamide subdermal implants are the products in more
      advanced stages of clinical development. Their pharmacokinetics/dynamics and
      safety/efficacy are reviewed. Expert commentary: In the absence of eradicative
      therapy for individuals with HIV infection and protective vaccines for persons at
      risk, long-term antiretroviral therapy is the best approach for preventing
      disease progression in patients and halting transmissions, either as result of
      'treatment as prevention' for HIV carriers or 'pre-exposure prophylaxis' for
      uninfected individuals at risk. In all these scenarios, the advent of long-acting
      antiretrovirals will expand options for overcoming the challenge of suboptimal
      drug adherence and reduce the burden of HIV infection.

PMID- 29595352
TI  - The inhibitory effect of functional lesions on eloquent brain areas: from
      research bench to operating bed.
AB  - OBJECTIVES: Functioning, but injured cerebral connections are hypothesized to
      inhibit cortical plasticity. Study of neural networks can validate this
      hypothesis, and provide further practical clues for clinical and surgical options
      to restore function in eloquent brain areas. MATERIAL AND METHODS: Cortical
      lesions in eloquent areas were simulated by means of artificial neural networks.
      Next, functional restoration of these networks after lesional bypass was studied.
      RESULTS: The accuracy of network outputs was reduced from 92% to 72% (P-value <
      0.001) when logical temporal connections with dysfunctional lesions were
      established. Restoration of function was almost totally achieved by bypassing the
      lesion, without any significant changes in network nodal weights. Estimated
      remaining functional fraction errors were trivial (0.0044%-1.4%). DISCUSSION:
      Examples of functional decline due to disturbing signals are Todd's paralysis and
      Landau-Kleffner syndrome. Functional restoration after lesionectomy in eloquent
      areas of the brain is also practiced. Likewise, injured connections provide
      routes of influence for disturbing impulses. CONCLUSION: Herein, the proposed
      evidences provide theoretical clues to formulate new avenues in restorative
      functional neurosurgery. They may help to identify suitable lesions and suitable
      techniques for functional restoration including dissection of disturbing
      connections, bridging and bypassing lesions that can be corroborated by
      simulation.

PMID- 29595353
TI  - The Estonian Cancer Registry: foundation and further history.

PMID- 29595354
TI  - Comparison of posterior occlusion between patients with anterior open bite and
      scissor deep bite.
AB  - Objective A minor alteration in the posterior occlusal height elicits a large
      transformation in the anterior vertical dimension. Thus, the present study was
      performed to determine whether a posterior cusp-to-cusp relation that increases
      the posterior vertical dimension contributes to an anterior open bite. Methods
      Study casts were examined from orthodontic patients aged 10 to 27 years, 21 with
      an open bite and 28 with a scissor deep bite. A logistic regression model was
      used to analyze the contribution of various factors to these two anterior
      occlusal patterns. The dental arch width and number of worn cusps were compared
      between the two groups. Results Patients with an open bite had a significantly
      higher incidence of a posterior buccal-lingual cusp-to-cusp relation, wider
      mandibular arch in the molar region, and larger numbers of worn maxillary buccal
      cusps and mandibular lingual cusps than patients with a scissor deep bite.
      Conclusions A posterior buccal-lingual cusp-to-cusp relation is associated with a
      larger anterior vertical dimension, such as that in patients with an open bite.

PMID- 29595355
TI  - Irreversible electroporation for the treatment of cardiac arrhythmias.
AB  - INTRODUCTION: Cardiac ablation is an established treatment modality for the
      management of patients with cardiac arrhythmias. Current approaches to cardiac
      ablation employ thermal based energy to achieve lesions (damage) within the
      heart. There are many shortcomings and limitations of thermal based approaches.
      Electroporation (DC energy) is a non-thermal alternative approach to ablation
      that has shown significant promise in animal studies. Areas covered: An extensive
      review of the literature on the application of electroporation for ablation (both
      cardiac and collateral cardiac tissue) was undertaken. This review explores
      irreversible electroporation as a cardiac ablation modality. Specifically, it
      focuses and explains the biophysics of electroporation, the limitations of
      current thermal based approaches and examines the current data published on
      electroporation cardiac ablation. Expert commentary: Electroporation is a fast
      growing novel ablation modality that has many advantages over current thermal
      based approaches. Current research in animal models shows its can be safely and
      efficaciously applied to the heart. Although further research is required,
      electroporation represents an appealing option for the ablation cardiac
      arrhythmias.

PMID- 29595356
TI  - Chorea revealing systemic lupus erythematosus in a 13-year old boy: A case report
      and short review of the literature.
AB  - Among the neurological manifestations of systemic lupus erythematosus (SLE),
      chorea is rare, presenting in less than 7% of the pediatric SLE patients. It can
      appear early in the onset of SLE, be the first or even the sole clinical feature
      of the illness and has strongly been associated with the presence of
      antiphospholipid antibodies. We report on the case of a 13-year old boy, admitted
      with acute onset chorea and finally diagnosed with SLE. Subsequently, we present
      a short review of the literature on the epidemiology, suggested pathogenesis,
      clinical presentation and treatment of this rare presentation of SLE.

PMID- 29595357
TI  - Defining Quality in EMS.

PMID- 29595360
TI  - Preface to history symposium special issue.

PMID- 29595359
TI  - Feline hyperaesthesia syndrome with self-trauma to the tail: retrospective study
      of seven cases and proposal for integrated multidisciplinary diagnostic approach.
AB  - Case series summary This was a retrospective study on the clinical features and
      response to treatment in seven cats with feline hyperaesthesia syndrome (FHS) and
      tail mutilation. FHS is a poorly understood disorder characterised by skin
      rippling over the dorsal lumbar area, episodes of jumping and running, excessive
      vocalisation, and tail chasing and self-trauma. The majority of the cats were
      young, with a median age of 1 year at the onset of clinical signs, male (n = 6)
      and with access to the outdoors (n = 5). Multiple daily episodes of tail chasing
      and self-trauma were reported in five cats, with tail mutilation in four cats.
      Vocalisation during the episodes (n = 5) and rippling of lumbar skin (n = 5) were
      also reported. Haematology, serum biochemistry, Toxoplasma gondii and feline
      immunodeficiency virus/feline leukaemia virus serology, MRI scans of brain,
      spinal cord and cauda equina, cerebrospinal fluid analysis and electrodiagnostic
      tests did not reveal any clinically significant abnormalities. A definitive final
      diagnosis was not reached in any of the cats, but hypersensitivity dermatitis was
      suspected in two cases. A variety of medications was used alone or in
      combination, including gabapentin (n = 6), meloxicam (n = 4) antibiotics (n = 4),
      phenobarbital (n = 2), prednisolone (n = 2) and topiramate (n = 2); ciclosporin,
      clomipramine, fluoxetine, amitriptyline and tramadol were used in one cat each.
      Clinical improvement was achieved in six cases; in five cats complete remission
      of clinical signs was achieved with gabapentin alone (n = 2), a combination of
      gabapentin/ciclosporin/amitriptyline (n = 1),
      gabapentin/prednisolone/phenobarbital (n = 1) or gabapentin/topiramate/meloxicam
      (n = 1). Relevance and novel information This is the first retrospective study on
      a series of cats with FHS. The diagnostic work-up did not reveal any significant
      abnormalities of the central or peripheral nervous system; dermatological and
      behavioural problems could not be ruled out. We propose an integrated
      multidisciplinary diagnostic pathway to be used for the management of clinical
      cases and for future prospective studies.

PMID- 29595358
TI  - Serum neutrophil gelatinase-associated lipocalin and cystatin C are diagnostic
      markers of renal dysfunction in older patients with coronary artery disease.
AB  - Objective This study aimed to assess the diagnostic value of serum neutrophil
      gelatinase-associated lipocalin (NGAL) and cystatin C for renal dysfunction in
      older patients with coronary disease. Methods A total of 84 older patients with
      coronary artery disease were included in this study. Serum NGAL and cystatin C
      levels were analysed using commercially available kits. Medical data of all
      patients were recorded and analysed. Results NGAL and cystatin C levels were
      significantly positively correlated with N-terminal prohormone of brain
      natriuretic peptide levels and negatively correlated with the estimated
      glomerular filtration rate. The areas under the receiver operating characteristic
      curves of serum NGAL and cystatin C levels for diagnosing early renal dysfunction
      were 0.884 and 0.744, respectively. Conclusion Serum NGAL and cystatin C are
      potential early and sensitive markers of renal dysfunction in older patients with
      coronary artery disease.

PMID- 29595361
TI  - Positive-blank versus negative-blank feedback learning in children and adults.
AB  - In positive-blank feedback learning, positive feedback is given to a correct
      response whereas blank feedback is given to an incorrect response. Conversely, in
      negative-blank feedback learning, blank feedback is given to a correct response
      and negative feedback to an incorrect response. As blank feedback might be
      subjectively interpreted as signalling a correct response, negative-blank
      feedback might be more informative than positive-blank feedback, and thus may
      result in better performance. However, positive-blank feedback might also be
      superior as it motivates the learner in lengthy tasks. These "information" and
      "motivation" accounts were tested in a two-block feedback learning paradigm. In
      the first block, that is, when the task duration was still short, children but
      not adults profited more from negative than from positive feedback. The results
      in children thus support the information account. In the second block, that is,
      when the task duration had become longer, children and adults profited more from
      positive feedback, thereby supporting the motivation account. Results are
      discussed in light of behavioural and neuroscientific theories on feedback
      learning.

PMID- 29595362
TI  - The framing effect in a monetary gambling task is robust in minimally verbal
      language switching contexts.
AB  - Decision-making biases, in particular the framing effect, can be altered in
      foreign language settings (foreign language effect) and following switching
      between languages (the language switching effect on framing). Recently, it has
      been suggested that the framing effect is only affected by foreign language use
      if the task is presented in a rich textual form. Here, we assess whether an
      elaborate verbal task is also a prerequisite for the language switching effect on
      framing. We employed a financial gambling task that induces a robust framing
      effect but is less verbal than the classical framing paradigms (e.g., the Asian
      disease problem). We conducted an online experiment ( n = 485), where we
      orthogonally manipulated language use and language switching between trials. The
      results showed no effects of foreign language use or language switching
      throughout the experiment. This online result was confirmed in a laboratory
      experiment ( n = 27). Overall, we find that language switching does not reduce
      the framing effect in a paradigm with little verbal content and thus that
      language switching effects seem contingent on the amount of verbal processing
      required.

PMID- 29595363
TI  - Emotion identification across adulthood using the Dynamic FACES database of
      emotional expressions in younger, middle aged, and older adults.
AB  - Facial stimuli are widely used in behavioural and brain science research to
      investigate emotional facial processing. However, some studies have demonstrated
      that dynamic expressions elicit stronger emotional responses compared to static
      images. To address the need for more ecologically valid and powerful facial
      emotional stimuli, we created Dynamic FACES, a database of morphed videos (n =
      1026) from younger, middle-aged, and older adults displaying naturalistic
      emotional facial expressions (neutrality, sadness, disgust, fear, anger,
      happiness). To assess adult age differences in emotion identification of dynamic
      stimuli and to provide normative ratings for this modified set of stimuli,
      healthy adults (n = 1822, age range 18-86 years) categorised for each video the
      emotional expression displayed, rated the expression distinctiveness, estimated
      the age of the face model, and rated the naturalness of the expression. We found
      few age differences in emotion identification when using dynamic stimuli. Only
      for angry faces did older adults show lower levels of identification accuracy
      than younger adults. Further, older adults outperformed middle-aged adults' in
      identification of sadness. The use of dynamic facial emotional stimuli has
      previously been limited, but Dynamic FACES provides a large database of high
      resolution naturalistic, dynamic expressions across adulthood. Information on
      using Dynamic FACES for research purposes can be found at http://faces.mpib
      berlin.mpg.de .

PMID- 29595364
TI  - Associations of alcohol use disorder, alcohol use, housing, and service use in a
      homeless sample of 255 individuals followed over 2 years.
AB  - BACKGROUND: Homeless individuals with alcohol use disorders have multiple
      comorbidities and therefore various service needs. Despite need for services,
      homeless individuals face numerous barriers to treatment. Little is known about
      the associations of specific services in relation to homelessness in the context
      of alcohol problems. The current study analyzed 2-year prospective longitudinal
      data on a homeless sample, examining relationships between alcohol use disorder,
      alcohol use, housing status, and service use over time. METHODS: Two hundred
      fifty-five of 400 individuals recruited systematically from shelters and street
      locations completed 3 annual assessments (69% completion). Data on lifetime and
      current psychiatric disorders, housing status, and past-year service use were
      obtained and merged with service use data gathered from local agencies.
      Generalized estimating equation (GEE) models were created to predict dependent
      outcome variables of stable housing, alcohol use, and service use in both follow
      up years. RESULTS: Lifetime alcohol use disorder was positively associated with
      substance and medical service use. Alcohol problems did not hinder attainment of
      stable housing, and placement in housing did not necessarily increase risk for
      alcohol use. Stable housing was negatively associated with psychiatric and
      substance service use. In the second year, when alcohol use was finally
      associated with receiving substance services, it appears that these services
      provided a gateway to psychiatric services. The psychiatric services in turn
      appeared to provide a gateway to medical services. CONCLUSIONS: Alcohol use
      behaved differently compared with lifetime alcohol use disorder in relation to
      service use. Lack of association between alcohol use and housing supports Housing
      First policy. Obtaining housing may have ameliorative effects on mental health,
      diminishing perceived need for psychiatric services. Services may also be more
      accessible during homelessness. Obtaining substance treatment may provide a
      gateway for those who use alcohol after becoming homeless to connect with
      psychiatric and medical services, informing policy and practice.

PMID- 29595365
TI  - Post-Brexit crystal ball gazing: The future for phase 1 clinical trials in the
      UK.

PMID- 29595366
TI  - Dabrafenib in combination with trametinib in the treatment of patients with BRAF
      V600-positive advanced or metastatic non-small cell lung cancer: clinical
      evidence and experience.
AB  - Mutations in the BRAF oncogene are found in 2-4% of all non-small cell lung
      cancer (NSCLC) patients. The most common activating mutation present within the
      BRAF oncogene is associated with valine substitution for glutamate at position
      600 (V600E) within the BRAF kinase. BRAF-targeted therapies are effective in
      patients with melanoma and NSCLC harboring BRAF V600E mutation. In both melanoma
      and NSCLC, dual inhibition of both BRAF and the downstream mitogen-activated
      protein kinase (MEK) improves response rates compared with BRAF inhibition alone.
      BRAF-MEK combination therapy (dabrafenib plus trametinib) demonstrated
      tolerability and efficacy in a recent phase II clinical trial and was approved by
      the European Medicines Agency and United States Food and Drug Administration for
      patients with stage IV NSCLC harboring BRAF V600E mutation. Here, in this review,
      we outline the preclinical and clinical data for BRAF and MEK inhibitor
      combination treatment for NSCLC patients with BRAF V600E mutation.

PMID- 29595367
TI  - Lessons learned from the implementation of a medically enhanced residential
      treatment (MERT) model integrating intravenous antibiotics and residential
      addiction treatment.
AB  - BACKGROUND: Hospitalizations for severe infections associated with substance use
      disorder (SUD) are increasing. People with SUD often remain hospitalized for many
      weeks instead of completing intravenous antibiotics at home; often, they are
      denied skilled nursing facility admission. Residential SUD treatment facilities
      are not equipped to administer intravenous antibiotics. We developed a medically
      enhanced residential treatment (MERT) model integrating residential SUD treatment
      and long-term IV antibiotics as part of a broader hospital-based addiction
      medicine service. MERT had low recruitment and retention, and ended after six
      months. The goal of this study was to describe the feasibility and acceptability
      of MERT, to understand implementation factors, and explore lessons learned.
      METHODS: We conducted a mixed-methods evaluation. We included all potentially
      eligible MERT patients, defined by those needing >=2 weeks of intravenous
      antibiotics discharged from February 1 to August 1, 2016. We used chart review to
      identify diagnoses, antibiotic treatment location, and number of recommended and
      actual IV antibiotic-days completed. We audio-recorded and transcribed key
      informant interviews with patients and staff. We conducted an ethnographic
      analysis of interview transcripts and implementation field notes. RESULTS: Of the
      45 patients needing long-term intravenous antibiotics, 18 were ineligible and 20
      declined MERT. 7 enrolled in MERT and three completed their recommended
      intravenous antibiotic course. MERT recruitment barriers included patient
      ambivalence towards residential treatment, wanting to prioritize physical health
      needs, and fears of untreated pain in residential. MERT retention barriers
      included high demands of residential treatment, restrictive practices due to PICC
      lines, and perceptions by staff and other residents that MERT patients "stood
      out" as "different." Despite the challenges, key informants felt MERT was a
      positive construct. CONCLUSIONS: Though MERT had many possible advantages; it
      proved more challenging to implement than anticipated. Our lessons may be
      applicable to future models integrating post-hospital intravenous antibiotics and
      SUD care.

PMID- 29595369
TI  - Corrigendum.

PMID- 29595368
TI  - The care of patients using methamphetamine in the emergency department:
      Perception of nurses, residents, and faculty.
AB  - BACKGROUND: To determine differences in perception between nurses, residents, and
      faculty regarding characteristics and treatment of patients who use
      methamphetamine (meth). METHODS: Survey study performed at an urban, university
      Level I trauma medical center. RESULTS: A total of 80 nurses, 39 residents, and
      45 faculty completed the survey. All groups agreed that meth was a significant
      problem nationwide and in our emergency department (ED). Nurses estimated that
      33% of their patients used meth, which differed from residents (18%) and faculty
      (15%). All agreed that these patients required more effort to care for, utilized
      more hospital resources, and were more often violent toward staff. Nurses
      reported higher prevalence of actual assault by patients using meth (70%) than
      did residents (36%) and faculty (47%), and total lifetime number of assaults. All
      agreed that patients using meth appropriated prehospital resources at a higher
      rate than nonusers, had a higher rate of recidivism, and longer ED length of
      stay. Nurses preferred antipsychotics over benzodiazepines for treatment of meth
      induced tachycardia and a lower threshold for treatment of associated
      hypertension than residents and faculty. For treatment of hypertension, nurses
      preferred beta-blockers and hydralazine over benzodiazepines. CONCLUSION: All
      agreed that meth use is a serious problem in our ED, with high resource
      utilization, recidivism, and violence against staff. Nurses experienced higher
      rates of assaults by patients using meth and differed with regard to their
      disposition and treatment. Treatment guidelines, strategies to mitigate violence
      towards staff, and interprofessional education may be beneficial, as the stakes
      of caring for these patients are high and preferences vary between caregivers.

PMID- 29595370
TI  - Social work students' service learning experiences with grandfamilies: contact,
      comfort, and attitudes.
AB  - One way to increase student learning about older adults and aging family issues
      is to engage in community-based field experiences. Results from pre- and post
      surveys with 29 Bachelors of Social Work students enrolled in a year-long
      practicum course to assess their change in the level of contact, comfort, and
      attitudes with older adults and grandfamilies (i.e., grandparents/kin and the
      children in their home) are discussed. Students who met with grandfamilies (n =
      9) were compared to students who met with older adults in a nursing home (n = 6)
      and students who met with children from an afterschool program or child treatment
      facility (n = 9). One-way ANOVA's revealed group differences in contact and
      quality of contact with grandfamilies. No significant differences were found for
      contact with older adults or comfort working with older adults and grandfamilies,
      or for attitudes toward older adults between the three groups. As a result of
      this project, educators should develop learning opportunities for students to
      increase their contact and comfort with older adults and aging families.

PMID- 29595371
TI  - Pathways to age-friendly communities in diverse urban neighborhoods: Do social
      capital and social cohesion matter?
AB  - Using a social capital and social cohesion lens, we reposition the concept of
      civic engagement among older adults to examine pathways for building age-friendly
      communities. We analyzed data drawn from a Community-Based Participatory Research
      study in the Southern U.S. that explored lived experiences of older adults, age
      55 and above, who participated in individual interviews (n = 15) and six focus
      group discussions (n = 45) to examine their perceptions of social identity,
      social connectedness, and civic engagement geared toward an age-friendly city.
      Findings indicated that several older adults had access to social networks and
      socially invested resources, thereby having opportunities for civic engagement
      and building age-friendly neighborhoods. However, social, cultural, linguistic,
      and structural barriers were more evident among certain diverse ethnic
      populations. Marginalized low-income minorities and immigrants, such as Hispanic
      participants, felt the lack of social cohesion among the larger society limited
      their ability to give back, thus decreasing their civic engagement activities. In
      contrast, Caucasian and African-American older adults were able to contribute to
      the political process through more civic participation activities. We provide
      implications for examining the role of social capital and social engagement to
      bolster civic engagement among older adults in building age-friendly communities.

PMID- 29595372
TI  - Financial abuse of older people in low and middle-income countries: the case of
      South Africa.

PMID- 29595373
TI  - Persistent organic pollutants and haematological markers in Greenlandic pregnant
      women: the ACCEPT sub-study.
AB  - The Arctic populations have high blood concentrations of persistent organic
      pollutants (POPs). Exposure to POPs was related to adverse health effects e.g.
      immune, neurological and reproductive systems. This study investigates
      associations between serum POP levels and haematological markers in Greenlandic
      pregnant women. This cross-sectional study included 189 women enrolled in 2010
      2011 at the Greenlandic West coast by the inclusion criteria >=18 years of age
      and had lived for 50% or more of their life in Greenland. The associations
      between the sum of the POP variables polychlorinated biphenyls (sumPCBs),
      organochlorine pesticides (sumOCPs), perfluoroalkylated substances (sumPFASs) and
      24 haematological markers were analysed using linear regression adjusted for age,
      pre-pregnancy BMI, parity, gestation week, plasma-cotinine and alcohol intake. It
      showed a significantly inverse association between several haematological markers
      (eosinophil, lymphocyte, neutrophil and white blood cells) and sumPCBs, sumOCPs
      and sumPFASs. In addition, the monocyte, mean corpuscular haemoglobin
      concentration, plateletcrit and platelet count markers were significantly
      inversely associated with sumPFASs, but the haematocrit and mean erythrocyte
      corpuscular volume were positively associated with sumPFASs. In conclusion,
      exposure to POPs influenced several haematological markers, especially cell count
      parameters, suggesting immunosuppressive potential of POPs in Greenlandic
      pregnant women. The data need further investigations.

PMID- 29595374
TI  - Procedures and complications in late-nineteenth-century experimental
      neuroanatomical research exemplified by articles of Henry Herbert Donaldson (1857
      1938).
AB  - Henry Herbert Donaldson (1857-1938) was a leader in neurological research in the
      United States for several decades, beginning about 1890. A detailed account of
      three of his earliest publications shows the neuroanatomical procedures involved
      in the study of the relation of brain and intelligence during the late-nineteenth
      century in America. Two of the articles, published in September 1890 and December
      1891, were titled, "Anatomical Observations on the Brain and Several Sense-Organs
      of the Blind Deaf-Mute, Laura Dewy Bridgman (1829-1889)"; the third, published in
      August 1892, used the information from the first two to delimit the extent of the
      visual processing area of the human cortex. Donaldson's procedures included brain
      cuttings and measures of macroscopic brain structures, histology of cellular
      structures, attempts to relate macroscopic brain structures with brain functions,
      data corrections, estimations, comparisons, and statistics. These procedures
      provide a view of the relative thoroughness, accuracy, and comparability of the
      various neuroanatomical techniques in use at that time and of Donaldson's
      implementation of the techniques. Donaldson's brain cutting techniques were much
      more comparable than his measurement techniques. The latter could be quite
      precise, but they were fraught with lack of standardized procedures that made
      corrections and estimations necessary when making data comparisons across
      studies. Donaldson emphasized these incompatibilities, implying a need for
      standardization. Statistical procedures were the least thorough and effective.
      His, and the field's, total complement of statistical techniques consisted of
      mean and range, which severely limited his ability to make complicated
      assessments. This limitation was not necessarily supplemented by stringent
      control group comparisons.

PMID- 29595375
TI  - Medications for Opioid Use Disorder in the Department of Veterans Affairs (VA)
      Health Care System: Historical Perspective, Lessons Learned and Next Steps.
AB  - The US Department of Veterans Affairs (VA), the largest health care system in the
      US, has been confronted with the health care consequences of opioid disorder
      (OUD). Increasing access to quality OUD treatment, including pharmacotherapy, is
      a priority for the VA. We examine the history of medications (e.g., methadone,
      buprenorphine, injectable naltrexone) used in the treatment of OUD within VA,
      document early and ongoing efforts to increase access and build capacity,
      primarily through the use of buprenorphine, and summarize research examining
      barriers and facilitators to prescribing and medication receipt. We find that
      there has been a slow but steady increase in the use of medications for OUD and,
      despite system-wide mandates and directives, uneven uptake across VA facilities
      and within patient sub-populations, including some of those most vulnerable. We
      conclude with recommendations intended to support the greater use of medication
      for OUD in the future, both within VA as well as other large health care systems.

PMID- 29595376
TI  - Application of an Ex Vivo Tissue Model to Investigate Radiobiological Effects on
      Spermatogenesis.
AB  - The formation of sperm by the testes through the process of spermatogenesis is
      highly radiosensitive and can be affected by environmental, occupational and
      therapeutic radiation exposures. In this study, we applied an ex vivo mouse
      testis organ culture as an experimental model of spermatogenesis to investigate
      the radiobiological effects and to demonstrate its feasibility as a tool to
      determine response to complex, modulated radiation fields. This model uses Acr
      GFP transgenic mice, which express the marker green fluorescent proteins specific
      for meiosis to allow observation of functional changes in real-time that can be
      used to analyze radiation-induced changes in the process of spermatogenesis. Our
      results showed that the model can accurately reproduce radiation-induced male
      germ cell toxicity, such as temporary infertility and permanent sterility.
      Furthermore, using a monochromatic X-ray microbeam, we applied this model to
      investigate the effects of heterogeneous radiation fields on testis tissue ex
      vivo. Our model represents a unique application in the field, which offers
      significant potential for gaining further mechanistic insight into radiation
      effects on the process of spermatogenesis.

PMID- 29595377
TI  - Procrastination, Flow, and Academic Performance in Real Time Using the Experience
      Sampling Method.
AB  - The authors' aim was to first provide an alternative methodology in the
      assessment of procrastination and flow that would not reply on retrospective or
      prospective self-reports. Using real-time assessment of both procrastination and
      flow, the authors investigated how these factors impact academic performance by
      using the Experience Sampling Method. They assessed flow by measuring student
      self-reported skill versus challenge, and procrastination by measuring the days
      to completion of an assignment. Procrastination and flow were measured for six
      days before a writing assignment due date while students (n = 14) were enrolled
      in a research methods course. Regardless of status of flow, both the nonflow and
      flow groups showed high levels of procrastination. Students who experienced flow
      as they worked on their paper, in real time, earned significantly higher grades
      (M = 3.05 +/- 0.30: an average grade of B) as compared with the nonflow group (M
      = 1.16 +/- 0.33: an average grade of D; p = .007). Additionally, students
      experiencing flow were more accurate in predicting their grade (difference
      scores, flow M = 0.12 +/- 0.33 vs. nonflow M = 1.39 +/- 0.29; p = .015). Students
      in the nonflow group were nearly a grade and a half off in their prediction of
      their grade on the paper. To the authors' knowledge, the study is the first to
      provide experimental evidence showing differences in academic performance between
      students experiencing flow and nonflow students.

PMID- 29595378
TI  - A systematic review of work-related musculoskeletal disorders among handicraft
      workers.
AB  - PURPOSE: Handicraft manufacturing appears to be an occupation where work-related
      musculoskeletal disorders (WMSDs) are a major threat to workers. For the
      multifactorial nature and varying prevalence of WMSDs between different body
      areas, the current study aimed to evaluate the prevalence of WMSDs and associated
      risk factors among handicraft workers. METHODS: This review was based on
      literature collected from three electronic databases, and the retrieved articles
      were screened following the inclusion/exclusion criteria. After applying the
      literature selection criteria to 182 articles, 30 citations were selected and
      examined in detail. RESULTS: The findings suggest that the prevalence of
      musculoskeletal symptoms among handicraft workers is 38.5-100%, and the most
      affected body areas were the neck, back, knees and upper limbs. Risk factors
      including working posture, daily working hours, repetitive and forceful
      movements, work experience, age, gender and working under stressful conditions
      were found to be highly associated with the occurrence of WMSDs. However, higher
      educational qualification of the workers led to a reduction in the odds of
      developing WMSDs. CONCLUSION: Handicraft workers are at high risk of developing
      WMSDs. Further research, preferably longitudinal studies, with more emphasis on
      work-related factors should now be undertaken to thoroughly investigate WMSDs in
      this occupational group.

PMID- 29595379
TI  - Child malnutrition in Ifanadiana district, Madagascar: associated factors and
      timing of growth faltering ahead of a health system strengthening intervention.
AB  - BACKGROUND: Child malnutrition, a leading cause of death and disability
      worldwide, is particularly severe in Madagascar, where 47% of children under 5
      years are stunted (low height-for-age) and 8% are wasted (low weight-for-height).
      Widespread poverty and a weak health system have hindered attempts to implement
      life-saving malnutrition interventions in Madagascar during critical periods for
      growth faltering. OBJECTIVE: This study aimed to shed light on the most important
      factors associated with child malnutrition, both acute and chronic, and the
      timing of growth faltering, in Ifanadiana, a rural district of Madagascar.
      METHODS: We analyzed data from a 2014 district-representative cluster household
      survey, which had information on 1175 children ages 6 months to 5 years. We
      studied the effect of child health, birth history, maternal and paternal health
      and education, and household wealth and sanitation on child nutritional status.
      Variables associated with stunting and wasting were modeled separately in
      multivariate logistic regressions. Growth faltering was modeled by age range. All
      analyses were survey-adjusted. RESULTS: Stunting was associated with increasing
      child age (OR = 1.03 (95%CI 1.02-1.04) for each additional month), very small
      birth size (OR = 2.32 (1.24-4.32)), low maternal weight (OR = 0.94 (0.91-0.97)
      for each kilogram, kg) and height (OR = 0.95 (0.92-0.99) for each centimeter),
      and low paternal height (OR = 0.95 (0.92-0.98)). Wasting was associated with
      younger child age (OR = 0.98 (0.97-0.99)), very small birth size (OR = 2.48 (1.23
      4.99)), and low maternal BMI (OR = 0.84 (0.75-0.94) for each kg/m2). Height-for
      age faltered rapidly before 24 months, then slowly until age 5 years, whereas
      weight-for-height faltered rapidly before 12 months, then recovered gradually
      until age 5 years but did not reach the median. CONCLUSION: Intergenerational
      transmission of growth faltering and early life exposures may be important
      determinants of malnutrition in Ifanadiana. Timing of growth faltering, in the
      first 1000 days, is similar to international populations; however, child growth
      does not recover to the median.

PMID- 29595380
TI  - EVALUATION OF ORAL RABIES VACCINATION: PROTECTION AGAINST RABIES IN WILD CAUGHT
      RACCOONS ( PROCYON LOTOR).
AB  - Oral rabies vaccination (ORV) is an effective tactic for wildlife rabies control,
      particularly for containment of disease spread along epizootic fronts. As part of
      the continuing evaluation of the ORV program in free-ranging raccoons ( Procyon
      lotor) in the US, 37 raccoons from ORV-baited areas in Pennsylvania were live
      trapped and transferred to captivity to evaluate protection against rabies in
      animals with varying levels of existing neutralizing antibodies, expressed in
      international units per milliliter (IU/mL). Among the 37 raccoons at the date of
      capture, 24% (9/37) of raccoons were seronegative (<0.05 IU/mL), 22% (8/37) were
      low positive (>=0.05-0.11 IU/mL), 27% (10/37) were medium positive (>0.11-<0.5
      IU/mL), and 27% (10/37) were high positive (>=0.5 IU/mL). Raccoons were held for
      86-199 d between the date of capture and rabies virus challenge. At challenge,
      68% (25/37) raccoons were seronegative. The overall survival rate among
      challenged animals was 46% (17/37). Based on the antibody titers at the time of
      challenge, survivorship was 24% (6/25) among seronegative animals, 100% (4/4)
      among low positive animals, 83% (5/6) among medium positive animals, and 100%
      (2/2) among high positive animals. Evidence of high-titer seroconversion after
      vaccination is a good surrogate indicator of rabies survival; however, survival
      rates of approximately 45% (15/35) were found among raccoons with detectable
      titers below 0.5 IU/mL. In contrast, any detectable titer at the time of
      challenge (>3 mo after vaccination) appeared to be a surrogate indicator of
      survival. Overall, we illustrated significant differences in the value of
      specific titers as surrogates for survival based on the timing of measurement
      relative to vaccination. However, survivorship was generally greater than 45%
      among animals with any detectable titer regardless of the timing of measurement.
      These findings suggest that lower titer cutoffs may represent a valid approach to
      measuring immunization coverage within ORV management zones, balancing both
      sensitivity and specificity for estimating herd immunity.

PMID- 29595381
TI  - Phylogenetic Analysis of Pigeon Paramyxoviruses Type-1 Identified in Mourning
      Collared-doves ( Streptopelia decipiens) in Namibia, Africa.
AB  - We generated the complete sequence of the fusion ( F) protein gene from six
      pigeon paramyxoviruses type 1 (PPMV-1) isolated from Mourning Collared-doves (
      Streptopelia decipiens) in Namibia, Africa between 2016 and 2017. All of the
      isolates had an F gene cleavage site motif of 112RRQKRF117 characteristic of
      virulent viruses. A phylogenetic analysis using the full F gene sequence revealed
      that the viruses belonged to genotype VIa and were epidemiologically related to
      PPMV-1s from Asia, Europe, and North America.

PMID- 29595382
TI  - Identification of Novel Gammaherpesviruses in a South American Fur Seal (
      Arctocephalus australis) with Ulcerative Skin Lesions.
AB  - There are few studies on pathogens affecting free-ranging pinnipeds from South
      America. We employed molecular techniques to identify a gammaherpesvirus
      infection by two putative novel herpesvirus species: Otariid herpesvirus 5 (OtHV
      5), possibly associated with ulcerative cutaneous lesions, and Otariid
      herpesvirus 6 (OtHV-6) in a wild South American fur seal ( Arctocephalus
      australis) that stranded alive in Santa Catarina state, southern Brazil. Here we
      provide new information regarding pinniped herpesviruses, important for the
      design of future disease surveillance studies.

PMID- 29595383
TI  - Mesocestoides sp. in Wild Northern Bobwhite ( Colinus virginianus) and Scaled
      Quail ( Callipepla squamata).
AB  - Mesocestoides spp. have a cosmopolitan distribution with zoonotic potential.
      Mesocestoides tetrathyridia were found under the pericardial sac, on the surface
      of the crop, and in the peritoneal cavity of a hunter-harvested Northern Bobwhite
      ( Colinus virginianus) and a Scaled Quail ( Callipepla squamata) collected during
      the 2016-17 quail hunting season in northwest and southern Texas, US
      respectively. Molecular analysis indicated that the tetrathyridia from the birds
      likely belonged to an undescribed species and are identical to pretetrathyridium
      stages recently found in Scincella lateralis skinks in Oklahoma. This is the
      first report of Mesocestoides from North American birds.

PMID- 29595385
TI  - Letters to the Editor.

PMID- 29595384
TI  - What Is Your Diagnosis?

PMID- 29595386
TI  - Outcomes of and risk factors for presumed canine H3N2 influenza virus infection
      in a metropolitan outbreak.
AB  - OBJECTIVE To determine clinical signs, case fatality rate, and factors associated
      with positive results of PCR testing for canine influenza virus (CIV) in dogs
      during an H3N2 CIV outbreak in the Atlanta area. DESIGN Cross-sectional study.
      ANIMALS 220 dogs with a nasal swab specimen submitted to an Atlanta-area
      diagnostic laboratory between May 1 and July 2, 2015, for PCR assay detection of
      CIV specifically or CIV and 5 other respiratory pathogens. PROCEDURES
      Veterinarians of tested dogs were surveyed by various means to collect
      information regarding clinical signs, survival status at the time of survey
      completion, vaccination history (<= 12 months prior to testing), and travel
      history (<= 2 months prior to testing). Data were compared between CIV-positive
      and CIV-negative dogs. RESULTS Surveys for 120 (55%) dogs were completed. Forty
      (33%) of these dogs had positive results of CIV testing. No significant
      differences were identified between CIV-positive and CIV-negative dogs regarding
      breed, sex, reproductive status, duration of clinical signs prior to testing,
      other dogs in the household, or travel history. When other factors were
      controlled for, CIV-positive dogs were more likely to be adult (> 1 year of age)
      than juvenile (<= 1 year of age) and to be inappetent. Only 1 (3%) CIV-positive
      dog died during the study period (shortly after it was evaluated because of
      respiratory signs). CONCLUSIONS AND CLINICAL RELEVANCE From May 1 to July 2,
      2015, the reported clinical signs of dogs tested during the Georgia H3N2 CIV
      outbreak were similar to those reported for dogs with H3N8 CIV infection, and the
      case fatality rate was low.

PMID- 29595387
TI  - Pathology in Practice.

PMID- 29595389
TI  - Rabies surveillance in the United States during 2016.
AB  - OBJECTIVE To describe rabies and rabies-related events occurring during 2016 in
      the United States. DESIGN Observational study based on passive surveillance data.
      ANIMALS All animals submitted for rabies testing in the United States during
      2016. PROCEDURES State and territorial public health programs provided data on
      animals submitted for rabies testing in 2016. Data were analyzed temporally and
      geographically to assess trends in domestic and sylvatic animal rabies cases.
      RESULTS During 2016, 50 states and Puerto Rico reported 4,910 rabid animals to
      the CDC, representing a 10.9% decrease from the 5,508 rabid animals reported in
      2015. Of the 4,910 cases of animal rabies, 4,487 (91.4%) involved wildlife.
      Relative contributions by the major animal groups were as follows: 1,646 (33.5%)
      bats, 1,403 (28.6%) raccoons, 1,031 (21.0%) skunks, 313 (6.4%) foxes, 257 (5.2%)
      cats, 70 (1.4%) cattle, and 58 (1.2%) dogs. There was a 4.6% decrease in the
      number of samples submitted for testing in 2016, compared with the number
      submitted in 2015. No human rabies deaths were reported in 2016. CONCLUSIONS AND
      CLINICAL RELEVANCE Laboratory testing of animals suspected to be rabid remains a
      critical public health function and continues to be a cost-effective method to
      directly influence human rabies postexposure prophylaxis recommendations.

PMID- 29595390
TI  - In This Issue * April 15, 2018.

PMID- 29595391
TI  - Ambulatory electrocardiographic evaluation of the occurrence of arrhythmias in
      healthy Salukis.
AB  - OBJECTIVE To determine the frequency and complexity of ventricular arrhythmias in
      a group of healthy Salukis evaluated by means of continuous Holter monitoring for
      7 days. DESIGN Prospective case series. ANIMALS 25 healthy Salukis > 18 months
      old. PROCEDURES In all dogs, a history was obtained and a physical examination
      and transthoracic echocardiography were performed to verify the absence of
      structural cardiac disease. Dogs then underwent Holter monitoring for 7 days.
      Data recorded included heart rate parameters and the occurrence of conduction
      disturbances, ventricular premature complexes, ventricular couplets, ventricular
      triplets, ventricular bigeminy, ventricular trigeminy, and ventricular
      tachycardia. RESULTS 25 dogs (13 sexually intact females, 2 spayed females, and
      10 sexually intact males) were enrolled in the study. All 25 dogs had at least
      one 24-hour period during which ventricular premature complexes were detected.
      Median number of ventricular premature complexes during any 24-hour period in all
      dogs was 2 (interquartile [25th to 75th percentile] range, 0 to 4). There were no
      significant differences between males and females in regard to median number of
      ventricular premature complexes per 24-hour period or recorded heart rate
      parameters. CONCLUSIONS AND CLINICAL RELEVANCE For Salukis in the study
      population, 7-day Holter monitoring revealed infrequent ventricular arrhythmias.
      These findings suggested that detection of a ventricular arrhythmia in a healthy
      Saluki may be an indication for further diagnostic evaluation.

PMID- 29595392
TI  - Theriogenology Question of the Month.

PMID- 29595393
TI  - New Veterinary Biologic Products.

PMID- 29595394
TI  - Comparison of thoracic duct ligation plus subphrenic pericardiectomy with or
      without cisterna chyli ablation for treatment of idiopathic chylothorax in cats.
AB  - OBJECTIVE To compare duration of surgery, recurrence rate, and survival time
      between cats with idiopathic chylothorax treated with thoracic duct ligation
      (TDL) plus subphrenic pericardiectomy (SPC) and those treated with TDL, SPC, and
      cisterna chyli ablation (CCA). DESIGN Retrospective case series with nested
      cohort study. ANIMALS 22 client-owned cats surgically treated for idiopathic
      chylothorax from 2009 through 2014. PROCEDURES Patient and surgery data were
      collected from the medical records. Recurrence of chylothorax and survival time
      were assessed by medical record review and client interview. Comparisons were
      made between cats treated with TDL plus SPC (TDL-SPC group) and those treated
      with TDL, SPC, and CCA (TDL-SPC-CCA group). RESULTS 15 cats were treated with TDL
      plus SPC, and 7 were treated with TDL, SPC, and CCA. Median duration of surgery
      was significantly briefer for the TDL-SPC group (80 minutes; range, 55 to 175
      minutes) than for the TDL-SPC-CCA group (125 minutes; range, 105 to 205 minutes).
      Five cats (2 in the TDL-SPC group and 3 in the TDL-SPC-CCA group) had persistent
      pleural effusion 4 weeks after surgery. Chylothorax recurred in 2 cats (1/group).
      Median survival time in the TDL-SPC group was 774 days (range, 3 to 2,844 days)
      and in the TDL-SPC-CCA group was 380 days (range, 11 to 815 days); these values
      did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Addition of CCA
      to the surgical treatment approach for cats with idiopathic chylothorax was
      associated with a significantly longer duration of surgery with no better outcome
      than achieved with TDL plus SPC alone.

PMID- 29595395
TI  - Pathology in Practice.

PMID- 29595396
TI  - Clinical findings and diagnostic test results for calves with septic arthritis:
      64 cases (2009-2014).
AB  - OBJECTIVE To describe clinical findings and diagnostic test results and identify
      potential prognostic indicators for calves with septic arthritis. DESIGN
      Retrospective case series. ANIMALS 64 calves with septic arthritis. PROCEDURES
      The medical record database for a veterinary teaching hospital was searched to
      identify calves <= 6 months old that were treated for septic arthritis between
      2009 and 2014. Data evaluated included signalment, history, physical examination
      and diagnostic test results, treatment, and outcome. Descriptive data were
      generated, and calves were assigned to 2 groups (neonatal [<= 28 days old] or
      postneonatal [29 to 180 days old]) on the basis of age at hospital admission for
      comparison purposes. RESULTS 64 calves had 92 infected joints; 17 calves had
      polyarthritis. Carpal joints were most frequently affected followed by the stifle
      and tarsal joints. Forty-nine bacterial isolates were identified from synovial
      specimens for 38 calves, and the most commonly identified isolates were catalase
      negative Streptococcus spp (n = 14) and Mycoplasma bovis (9). Calves in the
      neonatal group had a shorter interval between onset of clinical signs and
      hospitalization and were more likely to have an infected carpal joint than calves
      in the postneonatal group. Outcome was positive for 35 calves. Synovial fluid
      total nucleated cell count was positively associated with a positive outcome.
      CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that empirical antimicrobial
      treatment for calves with septic arthritis should target gram-positive catalase
      negative cocci and M bovis and that synovial fluid total nucleated cell count
      might be a useful prognostic indicator.

PMID- 29595397
TI  - Rostral mandibular fracture repair in a pet bearded dragon (Pogona vitticeps).
AB  - CASE DESCRIPTION A 2-year-old male bearded dragon (Pogona vitticeps) was
      evaluated because of a traumatic mandibular fracture. CLINICAL FINDINGS An open
      comminuted fracture of the rostral aspect of the right mandible was evident, with
      a fragment of bone exposed and dorsally displaced. Whole-body radiography
      revealed no evidence of additional injury. Other findings were unremarkable,
      except for moderate anemia (PCV, 19%). TREATMENT AND OUTCOME The fracture
      fragments were stabilized with 2 crossed 36-gauge interfragmentary wire loops. An
      external fixator device was fashioned from four 25-gauge needles inserted at
      alternating angles through the fracture fragments; plastic IV fluid line tubing
      filled with dental acrylic was used as a connecting bar. One day after surgery,
      the lizard had regained its typical activity level and appetite. Body weight was
      measured and the external fixator was inspected 1 week after surgery and monthly
      thereafter. Three months after initial injury, the fracture was stable,
      radiography revealed bony callus formation at the fracture site, and the external
      fixator was removed. Recheck radiography performed 5.5 months after initial
      injury revealed complete osseous union of the fracture fragments, and the
      interfragmentary wires were removed. CLINICAL RELEVANCE Surgical management of
      the traumatic comminuted mandibular fracture in this bearded dragon by means of a
      combination of internal and external fixation resulted in complete healing of the
      mandible and restoration of function. Management of this complicated fracture was
      achieved with the aid of readily available and inexpensive supplies in a clinical
      setting, which may be useful to other clinicians in the management of similar
      cases.

PMID- 29595398
TI  - Outcome of elective cholecystectomy for the treatment of gallbladder disease in
      dogs.
AB  - OBJECTIVE To determine mortality rates for dogs undergoing cholecystectomy and
      variables associated with failure to survive to hospital discharge. DESIGN
      Retrospective cohort study. ANIMALS 70 dogs that underwent cholecystectomy for
      biliary tract disease at a companion animal referral hospital from 2009 through
      2015. PROCEDURES Medical records of dogs were reviewed and data collected; dogs
      with biliary diversion surgery were excluded. Included dogs were grouped by
      whether cholecystectomy had been elective (ie, dogs with no or mild clinical
      signs, with no indication of biliary obstruction, or that initially underwent
      surgery for a different procedure) or nonelective (ie, dogs with icterus and
      questionable patency of the biliary system). Mortality rates (proportions of dogs
      that failed to survive to hospital discharge) were compared between various
      groups. RESULTS 45 (64%) dogs were included in the elective group and 25 (36%) in
      the nonelective group. Group mortality rates were 2% (1/45) and 20% (5/25),
      respectively, and differed significantly. Overall mortality rate was 9% (6/70).
      Serum albumin concentration was significantly lower and serum alanine
      aminotransferase activity and total bilirubin concentration were significantly
      higher in nonsurviving versus surviving dogs. Dogs with vomiting, signs of
      lethargy or anorexia, icterus, or azotemia were less likely to survive than dogs
      without these signs. CONCLUSIONS AND CLINICAL RELEVANCE Dogs that underwent
      elective cholecystectomy had a considerably lower mortality rate than previously
      reported. Elective cholecystectomy may be an appropriate recommendation for dogs
      with early signs of biliary disease to avoid the greater mortality rate
      associated with more advanced disease and nonelective cholecystectomy.

PMID- 29595399
TI  - Functionality of a novel follitropin alfa pen injector: results from human factor
      interactions by patients and nurses.
AB  - OBJECTIVE: The main objective of this user experience testing study was to
      evaluate the impact of human factors on the use of a disposable pen containing
      follitropin alfa by patients and nurses with special focus on the convenience,
      safety and ease of use, in different types of stimulation protocols. METHODS:
      Infertile women trying to conceive, and specialist nurses were recruited across 6
      European countries. In total 18 patients and 19 nurses took part in the testing,
      which included both nurse-patient pairings and in-depth interviews. A
      standardized list of expected and pre-defined critical steps according to the
      Instructions for Use (IFU), was used to assess the correct handling of the pen.
      RESULTS: During the user experience testing, no critical errors, related to the
      use of the pen, which could affect the success of the injection process were
      identified. In general, both nurses and patients found the pen very easy to
      learn, use and would be confident using the pen for self-injection. Nurses also
      found the pen very easy to train the patients. CONCLUSIONS: The study provides
      valuable information on the pen from both patient and nurse perspectives in
      different simulated scenarios reflecting standard practice.

PMID- 29595400
TI  - Lack of knowledge and training are the major obstacles in application of the
      Spinal Cord Independence Measure (SCIM) in China.
AB  - Objective To investigate the use of functional outcome measurements after spinal
      cord injury (SCI) in current clinical practice and to explore the knowledge about
      the Spinal Cord Independence Measure (SCIM) among SCI physicians in China, and to
      find facilitators for a broader utilization of SCIM. Design A survey-based study.
      Setting SCI workshops at Peking University. Participants 125 Chinese SCI
      physicians attending annual workshops in two consecutive years. Interventions Not
      applicable. Outcome measures A questionnaire was administered. The following
      items were included: whether functional outcome measurement for SCI individuals
      was performed and with which assessment tool(s); what items should be included in
      the assessment; whether they knew about the SCIM, its latest version, the Chinese
      translation, and if so from what source; the possible reasons why SCIM was not
      implemented in clinical practice; and whether training before using the SCIM was
      needed, and the training method preferred. Results Among these physicians, 84.8%
      performed functional outcome measurement for individuals with SCI, but only 29.6%
      of attendees were aware of the SCIM and 20.8% had used it. Lack of training was
      the major reason why SCIM was not used in clinical practice. Furthermore, 74.4%
      of the physicians felt they needed formal training before using the SCIM.
      Conclusion The use of SCIM is limited in clinical practice in China, which is
      mainly attributed to lack of knowledge and training. Formal training on the use
      of the SCIM is essential for its dissemination and will improve functional SCI
      outcome measurement in China.

PMID- 29595401
TI  - Epidemiological profile of thoracolumbar fracture (TLF) over a period of 10 years
      in Tianjin, China.
AB  - CONTEXT/OBJECTIVE: The objective of the research was to illustrate the
      epidemiology profile of thoracolumbar fracture (TLF) in Tianjin Medical
      University General Hospital, China, from 2006-2015. DESIGN: Hospital-based
      retrospective study. SETTING: Tianjin Medical University General Hospital.
      METHODS: Medical records of inpatient patients with TLF from 1 January 2006 to
      December 2015 were collected. Detailed information on epidemiological characters
      were analyzed based on the medical records suffering from TLF from T11-L2 level,
      including incidence, age and sex, marital, occupation, etiology and fracture
      type, types of injuries. RESULTS: Totally 132 cases were identified. The
      incidence rate was 2.4 patient per million population at 2015. Male-to-female
      ratio was 1.4:1, with a mean age of 49.1 +/- 17.7 years. The cases number in 46
      60 group, totally 35 and accounting for 26.5%, was the largest. There is a
      significant differences of cases number between 2011-2015 group and 2006-2010
      group. Retiree, taken up 48.5%, was the largest group among TLF patients. The
      most common injury level was T12 (34) accounting for 25.7%. Falls (57, 43.2%)
      (low falls and high falls) were the leading causes, followed by motor vehicle
      collisions (MVCs) (23, 17.4%).Compression is the only type of osteoporosis and
      took up 55.3%. CONCLUSIONS: The incidence ratio is increased annually in TMUGH.
      Male was more vulnerable than female based on different social character. The
      average age was older in 2011-2015, retiree accounted for the main proportion and
      compression took up the largest percentage, the mean age increased and
      osteoporosis takes more in recent years.

PMID- 29595402
TI  - Implementing single-item screening for drug use in a Veterans Health
      Administration outpatient setting.
AB  - BACKGROUND: Unhealthy drug use is a concern in many settings, including military
      and veteran populations. In 2013, the Veterans Health Administration (VHA)
      medical center in Bedford, Massachusetts, started requiring routine screening for
      unhealthy drug use in outpatient primary care and mental health settings, using a
      validated single question. METHODS: This study used descriptive and multivariable
      analyses of VHA electronic records for patients eligible for the screening
      program (N = 16,118). The study assessed first-year rates and predictors of
      screening and of positive screens, both for drug use and for unhealthy alcohol
      use, for which screening was already required. RESULTS: During the first year,
      70% of patients were screened for unhealthy drug use and 84% were screened for
      unhealthy alcohol use. In multivariable analyses, screening for drug use was more
      likely for patients who had 8 or more days with VHA visits or were aged 40 or
      over. Patients with a prior drug use disorder diagnosis were much less likely to
      be screened. Three percent of patients screened for unhealthy drug use had a
      positive screen, and 14% of those screened for unhealthy alcohol use had a
      positive screen. Strong predictors of a positive drug use screen included a prior
      year diagnosis of drug use disorder, any mental health clinic visits, younger
      age, or being unmarried. CONCLUSIONS: The drug screening initiative was
      relatively successful in its first-year implementation, having screened 70% of
      eligible subjects. However, it failed to screen many of those most likely to
      screen positive, thereby missing many opportunities to address unhealthy drug
      use. Future refinements should include better training clinicians in how to ask
      sensitive questions and how to address positive screens.

PMID- 29595403
TI  - Factors associated with contingency management adoption among opioid treatment
      providers receiving a comprehensive implementation strategy.
AB  - BACKGROUND: Contingency management (CM) is an evidence-based behavioral
      intervention for opioid use disorders (OUDs); however, CM adoption in OUD
      treatment centers remains low due to barriers at patient, provider, and
      organizational levels. In a recent trial, OUD treatment providers who received
      the Science to Service Laboratory (SSL), a multilevel implementation strategy
      developed by a federally funded addiction training center, had significantly
      greater odds of CM adoption than providers who received training as usual. This
      study examined whether CM adoption frequency varied as a function of provider
      sociodemographic characteristics (i.e., age, race/ethnicity, licensure) and
      perceived barriers to adoption (i.e., patient-, provider-, organization-level)
      among providers receiving the SSL in an opioid treatment program. METHODS: Thirty
      nine providers (67% female, 77% non-Hispanic white, 72% with specialty licensure,
      Mage = 42 [SD = 11.46]) received the SSL, which consisted of didactic training,
      performance feedback, specialized training of internal change champions, and
      external coaching. Providers completed a comprehensive baseline assessment and
      reported on their adoption of CM biweekly for 52 weeks. RESULTS: Providers
      reported using CM an average of nine 2-week intervals (SD = 6.35). Hierarchical
      multiple regression found that providers identifying as younger, non-Hispanic
      white, and without addiction-related licensure all had higher levels of CM
      adoption frequency. Higher perceived patient-level barriers predicted lower
      levels of CM adoption frequency, whereas provider- and organization-level
      barriers were not significant predictors. CONCLUSIONS: The significant effect of
      age on CM adoption frequency was consistent with prior research on predictors of
      evidence-based practice adoption, whereas the effect of licensure was counter to
      prior research. The finding that CM adoption frequency was lower among
      racially/ethnically diverse providers was not expected and suggests that the SSL
      may require adaptation to meet the needs of diverse opioid treatment providers.
      Entities using the SSL may also wish to incorporate a more explicit focus on
      patient-level barriers.

PMID- 29595404
TI  - Association between genetic variants in p53 binding sites and risks of
      osteosarcoma in a Chinese population: a two-stage case-control study.
AB  - Osteosarcoma (OS) is one of the most common bone malignancies in children and
      adolescents. To date, inaugural mechanism of OS was considered as a complex
      process and was still not clear. The p53 gene, most important tumor suppressors,
      was associated with risk of many tumors, including OS. In current study, we
      evaluated the relationship between genetic variation of the p53 binding site and
      the OS susceptibility through a two-stage case-control study in Chinese
      population. We found that rs1295925 (OR = 0.85; 95 CI = 0.76-0.94; P = 0.003) and
      rs3787547 (OR = 1.27; 95 CI = 1.11-1.45; P = 4.0 * 10-4) was significantly with
      OS susceptibility. Compared with those with rs1295925-TT genotype, and the risk
      of OS was significantly lower in individuals with CT genotype (OR = 0.77; 95 CI =
      0.65-0.92) and CC genotype (OR = 0.75; 95 CI = 0.60-0.93). Compared with those
      with rs3787547-GG genotype, and the risk of OS was significantly higher in
      individuals with AG genotype (OR = 1.32; 95 CI = 1.10-1.58) and AA genotype (OR =
      1.46; 95 CI = 1.11-1.92). To sum up, our results prove that SNP rs1295925 and
      rs3787547 play an important role in the etiology of OS, suggesting them as the
      potential genetic modifier for OS development.

PMID- 29595405
TI  - Prevalence and Risk Factors of Brucellosis, Chlamydiosis, and Bluetongue Among
      Sika Deer in Jilin Province in China.
AB  - Brucellosis and chlamydiosis are important zoonotic diseases and bluetongue virus
      (BTV) is an arthropod-borne viral disease of ruminants. They are widely
      distributed around the world, cause large economic losses, and significant
      harmful effects on humans. However, epidemiological information relating to
      transmission from commercial sika deer in China is limited. Therefore, from 2016
      to 2017, 458 sika deer blood samples were collected from three cities in Jilin
      Province in China. The Brucella antigen and specific antibodies to Chlamydia and
      BTV were examined using RT-PCR, indirect hemagglutination assay, and ELISA,
      respectively. The prevalence of Brucella was found to be 12.9% (59/458) and the
      seroprevalence of Chlamydia and BTV was 14.4% (66/458) and 17.0% (78/458),
      respectively. Seasonality was considered a risk factor for the presence of
      Brucella or BTV in sika deer and the region was considered a risk factor for
      Chlamydia infection. These data provides reference values for both further
      research and disease control.

PMID- 29595406
TI  - Distribution of the Mosquito Communities (Diptera: Culicidae) in Oviposition
      Traps Introduced into the Atlantic Forest in the State of Rio de Janeiro, Brazil.
AB  - The Atlantic Rainforest of South America is one of the major biodiversity
      hotspots of the world and serves as a place of residence for a wide variety of
      Culicidae species. Mosquito studies in the natural environment are of
      considerable importance because of their role in transmitting pathogens to both
      humans and other vertebrates. Community diversity can have significant effects on
      the risk of their disease transmission. The objective of this study was to
      understand the distribution of mosquito communities using oviposition traps in a
      region of the Atlantic Forest. Sampling was carried out in Bom Retiro Private
      Natural Reserve (RPPNBR), located in Casimiro de Abreu, Rio de Janeiro, using
      oviposition traps, which were set in the forest environment, from October 2015 to
      December 2016. The canonical correspondence analysis was used to assess the
      influence of the climatic variables (precipitation, maximum dew point, and
      direction) throughout the seasons on the population density of the mosquito
      species. The results showed that population density was directly influenced by
      climatic variables, which acted as a limiting factor for the mosquito species
      studied. The climatic variables that were significantly correlated with the
      density of the mosquito species were precipitation, maximum dew point, and
      direction. Haemagogus janthinomys was positively correlated with the three
      climatic variables, whereas Haemagogus leucocelaenus was positively correlated
      with precipitation and maximum dew point, and negatively correlated with
      direction.

PMID- 29595407
TI  - Chlamydiosis in Backyard Chickens (Gallus gallus) in Italy.
AB  - Until recently, Chlamydia psittaci was considered to be the only etiological
      agent of avian chlamydiosis, but two new avian species, Chlamydia gallinacea and
      Chlamydia avium, have recently been described in poultry and pigeons or
      psittacine birds, respectively. The aim of this study was to explore the
      occurrence of C. psittaci and C. gallinacea in backyard chickens in Italy.
      Cloacal swabs were taken from 160 asymptomatic chickens reared in 16 backyard
      farms. Samples were tested for C. psittaci and C. gallinacea by specific real
      time polymerase chain reaction assays, with 24 (15%) of the 160 chickens
      resulting positive for C. gallinacea. To attempt chlamydial isolation, new
      samples were obtained from two farms harboring a high prevalence (60% and 70%,
      respectively) of C. gallinacea-positive chickens. In total, eight C. gallinacea
      and one C. psittaci isolates were successfully recovered from 13 chickens. C.
      gallinacea was confirmed to be the endemic chlamydial species in chickens, with a
      high ompA intraspecies diversity. The presence of viable C. psittaci and C.
      gallinacea demonstrated by isolation from chickens in backyard farms poses a
      potential public health problem.

PMID- 29595408
TI  - An electronic intervention to improve safety for pain patients co-prescribed
      chronic opioids and benzodiazepines.
AB  - BACKGROUND: Co-prescribing opioids and benzodiazepines increases overdose risk. A
      paucity of literature exists evaluating strategies to improve safety of co
      prescribing. This study evaluated an electronic intervention to improve safety
      for patients co-prescribed chronic opioids for pain and benzodiazepines at 3 and
      6 months. METHODS: A prospective cohort study was conducted from December 2015
      through May 2016 at San Francisco Veterans Affairs Health Care System. A clinical
      dashboard identified 145 eligible patients prescribed chronic opioids and
      benzodiazepines. Individualized taper and safety recommendations were
      communicated to prescribers via electronic medical record progress note and
      encrypted e-mail at baseline. Primary outcome was number of patients co
      prescribed chronic opioids and benzodiazepines. Secondary outcomes included daily
      dose of opioids and benzodiazepines and number prescribed >=100 mg morphine
      equivalent daily dose. Safety outcomes included number with opioid overdose
      education and naloxone distribution, annual urine drug screening, annual
      prescription drug monitoring program review, and signed opioid informed consent.
      Linear mixed models and generalized estimating equations were used to examine
      within-group change in outcomes between baseline and 3 and 6 months. RESULTS:
      Among the 145 patients, mean (standard deviation) age was 62 (11) years and 91.7%
      (133/145) were male. Number co-prescribed significantly decreased from 145/145
      (100%) at baseline to 93/139 (67%) at 6-month follow-up (odds ratio [OR] = 0.53,
      95% confidence interval [CI]: 0.34-0.81, P = .003). Mean opioid and
      benzodiazepine doses significantly decreased from 84.61 to 65.63 mg (95% CI: 8.32
      27.86, P < .001) and from 16.10 to 13.45 mg (95% CI: 1.6-3.9, P < .001),
      respectively, from baseline to 6-month follow-up. Patients prescribed >=100 mg
      morphine equivalent daily dose significantly decreased from 39/145 (26.8%) at
      baseline to 26/139 (18.7%) at end of study (OR = 0.59, 95% CI: 0.44-0.78, P <
      .001), and patients with opioid overdose education and naloxone distribution
      significantly increased from 3/145 (2.1%) at baseline to 46/139 (33.1%; OR =
      23.4, 95% CI: 7.61-71.99, P < .001) by the end of study. Number of patients with
      annual urine drug screening tended to increase from 123/145 (84.8%) at baseline
      to 132/145 (91.4%) by the end of study (OR = 1.89, 95% CI: 0.95-3.76, P = .07),
      and there were no significant changes across time in numbers of patients with
      annual prescription drug monitoring program review or signed opioid informed
      consent. CONCLUSIONS: Electronic interventions may provide an effective strategy
      to improve safety for patients co-prescribed chronic opioids for pain and
      benzodiazepines.

PMID- 29595409
TI  - Influence of effective stress and dry density on the permeability of municipal
      solid waste.
AB  - A landfill is one of the main sites for disposal of municipal solid waste and the
      current landfill disposal system faces several problems. For instance, excessive
      leachate water is an important factor leading to landfill instability.
      Understanding the permeability characteristics of municipal solid waste is a
      relevant topic in the field of environmental geotechnical engineering. In this
      paper, the current research progress on permeability characteristics of municipal
      solid waste is discussed. A review of recent studies indicates that the research
      in this field is divided into two categories based on the experimental method
      employed: field tests and laboratory tests. This paper summarizes test methods,
      landfill locations, waste ages, dry densities and permeability coefficients
      across different studies that focus on permeability characteristics.
      Additionally, an experimental study on compressibility and permeability
      characteristics of fresh municipal solid waste under different effective stresses
      and compression times was carried out. Moreover, the relationships between the
      permeability coefficient and effective stress as well as dry density were
      obtained and a permeability prediction model was established. Finally, the
      experimental results from the existing literature and this paper were compared
      and the effects of effective stress and dry density on the permeability
      characteristics of municipal solid waste were summarized. This study provides the
      basis for analysis of leachate production in a landfill.

PMID- 29595410
TI  - A novel approach to treating adolescents with opioid use disorder in pediatric
      primary care.
AB  - BACKGROUND: Medication treatment for opioid use disorder is effective, and is
      recommended for adolescents, although very few adolescents with opioid use
      disorder ever receive medications. Reasons include lack of trained medication
      prescribers for this age group and difficulty in identifying adolescents with
      substance use disorders. This paper examines a novel implementation model of
      identifying and providing treatment for substance use disorders, including opioid
      use disorder, in a pediatric primary care practice. METHODS: Patients presenting
      to a selected primary care pediatrics practice for any reason between March 9,
      2017, and July 24, 2017, who were identified by screening, self-report, or other
      clinical information to have a substance use problem were referred to an
      integrated clinical social worker for treatment. The authors recorded the number
      of patients who were referred, number of visits completed, and substance use
      disorder and mental health diagnoses. RESULTS: In the first 4 months of this
      program, 683 patients aged 12-22 completed a health maintenance appointment; 20
      were referred for substance use disorder treatment and 13 completed at least 1
      substance use disorder treatment visit with the integrated clinical social
      worker. The mean number of visits completed was 5.3. Three patients with opioid
      use disorders were identified, and 2 were induced on buprenorphine. CONCLUSIONS:
      The current model for treatment of substance use disorders, including opioid use
      disorders, was feasible and acceptable in a pediatric primary care practice.
      Broadly implemented, such a model could substantially increase access to
      substance use disorder treatment for adolescents and young adults.

PMID- 29595411
TI  - Comparison of relative and absolute values of magnetic resonance imaging in the
      diagnosis of spinal epidural lipomatosis.
AB  - Objective To describe spinal epidural lipomatosis (SEL) of the lumbar region and
      evaluate the relative versus absolute values of epidural fat (EF) to determine
      which is more appropriate when using magnetic resonance imaging (MRI). Design
      Comparative study. Setting Hospital. Participants Eight SEL patients and 40
      healthy adults. Interventions MRI measurement of EF. Outcome Measures The MRI
      based EF thickness, cutoff value, and coefficient of variation (CV) were
      calculated. Frequency distribution maps for the absolute EF value and the
      relative EF/DuS value were created. Results SEL involved L3 - L4 in all cases.
      The mean EF thickness was 12.11 +/- 2.28 mm (range: 9.91 - 16.86 mm), and the
      average diameter of the dural sac (DuS) was 20.02 +/- 2.64 mm; the EF/DuS ratio
      was 0.61 +/- 0.03. In controls, the average EF thickness was 7.35 +/- 1.68 mm
      (range: 4.81 - 10.92 mm), and the average DuS was 20.86 +/- 2.11 mm; the EF/DuS
      ratio was 0.35 +/- 0.08. The relative and absolute values were significantly
      higher in the SEL group than in the normal group. A cutoff value of 9.8 mm could
      distinguish SEL patients from normal individuals. For the SEL group, the CV of
      the relative values (4.9%) was lower than that of the absolute values (18.8%).
      The frequency distribution map showed that the distribution of relative values
      was more concentrated than that of the absolute values for both groups.
      Conclusion Based on the frequency distribution and CVs, the relative value of
      EF/DuS maybe a better measure for diagnosing SEL than the absolute EF value.

PMID- 29595412
TI  - Out of Asia: the independent rise and global spread of fluoroquinolone-resistant
      Shigella.
AB  - Shigella are ranked among the most prevalent aetiologies of diarrhoeal disease
      worldwide, disproportionately affecting young children in developing countries
      and high-risk communities in developed settings. Antimicrobial treatment, most
      commonly with fluoroquinolones, is currently recommended for Shigella infections
      to alleviate symptoms and control disease transmission. Resistance to
      fluoroquinolones has emerged in differing Shigella species (S. dysenteriae,
      flexneri and sonnei) since the turn of the 21st century, originating in endemic
      areas, and latterly spreading into non-endemic regions. Despite occurring
      independently, the emergence of fluoroquinolone resistance in these different
      Shigella species shares striking similarities regarding their epidemiology and
      resistance mechanisms. Here, we review and discuss the current epidemiology of
      fluoroquinolone-resistant Shigella species, particularly in the light of recent
      genomic insights.

PMID- 29595413
TI  - Pseudomonas furukawaii sp. nov., a polychlorinated biphenyl-degrading bacterium
      isolated from biphenyl-contaminated soil in Japan.
AB  - Strain KF707T was isolated from a biphenyl-contaminated site in Kitakyushu,
      Japan. Analysis of 16S rRNA gene sequences, retrieved from the whole-genome
      sequence, revealed that the isolate was closely related to members of the genus
      Pseudomonas, sharing the highest sequence similarities with Pseudomonas balearica
      strain SP1402T (DSM 6083) (97.8 %). The DNA G+C chromosome and plasmid content of
      strain KF707T were 65.5 and 60.5 mol%. The major cellular fatty acids were iso
      C15 :  0 and C16 : 1omega7c/C16 : 1omega6c. Polyphasic analysis indicated that
      strain KF707T represents a novel species of the genus Pseudomonas, for which the
      name Pseudomonas furukawaii sp. nov. is proposed. The type strain is KF707T (=DSM
      10086T=NBRC 110670T).

PMID- 29595414
TI  - The FlaG regulator is involved in length control of the polar flagella of
      Campylobacter jejuni.
AB  - Campylobacter jejuni cells have bipolar flagella. Both flagella have similar
      lengths of about one helical turn, or 3.53+/-0.52 um. The flagellar filament is
      composed of two homologous flagellins: FlaA and FlaB. Mutant strains that express
      either FlaA or FlaB alone produce filaments that are shorter than those of the
      wild-type. It is reported that the flaG gene could affect filament length in some
      species of bacteria, but its function remains unknown. We introduced a flaG
      deletion mutation into the C. jejuni wild-type strain and flaA- or flaB-deletion
      mutant strains, and observed their flagella by microscopy. The DeltaflaG mutant
      cells produced long filaments of two helical turns in the wild-type background.
      The DeltaflaAG double mutant cells produced very short FlaB filaments. On the
      other hand, DeltaflaBG double mutant cells produced long FlaA filaments and their
      morphology was not helical but straight. Furthermore, FlaG was secreted, and a
      pulldown assay showed that sigma factor 28 was co-precipitated with purified
      polyhistidine-tagged FlaG. We conclude that FlaG controls flagella length by
      negatively regulating FlaA filament assembly and discuss the role of FlaA and
      FlaB flagellins in C. jejuni flagella formation.

PMID- 29595416
TI  - Proposal for a new classification of a deep branching bacterial phylogenetic
      lineage: transfer of Coprothermobacter proteolyticus and Coprothermobacter
      platensis to Coprothermobacteraceae fam. nov., within Coprothermobacterales ord.
      nov., Coprothermobacteria classis nov. and Coprothermobacterota phyl. nov. and
      emended description of the family Thermodesulfobiaceae.
AB  - The genus Coprothermobacter (initially named Thermobacteroides) is currently
      placed within the phylum Firmicutes. Early 16S rRNA gene based phylogenetic
      studies pointed out the great differences between Coprothermobacter and other
      members of the Firmicutes, revealing that it constitutes a new deep branching
      lineage. Over the years, several studies based on 16S rRNA gene and whole genome
      sequences have indicated that Coprothermobacter is very distant phylogenetically
      to all other bacteria, supporting its placement in a distinct deeply rooted novel
      phylum. In view of this, we propose its allocation to the new family
      Coprothermobacteraceae within the novel order Coprothermobacterales, the new
      class Coprothermobacteria, and the new phylum Coprothermobacterota, and an
      emended description of the family Thermodesulfobiaceae.

PMID- 29595417
TI  - Genotypic characterization of Haemophilus influenzae isolates from paediatric
      patients in Japan.
AB  - PURPOSE: beta-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus
      influenzae is frequently isolated from respiratory samples and is particularly
      problematic in Japan. The aim of this study was to characterize circulating
      isolates of H. influenzae genotypically by BLNAR-PCR and multilocus sequence
      typing (MLST), and to determine any associations between them. METHODS: H.
      influenzae isolates (n=191) were collected from paediatric patients (1 month to
      12 years old) between 2000 and 2011 for three types of infections: pneumonia
      (n=61), acute otitis media (AOM) (n=68) and meningitis (n=62). All were
      characterized for capsular type by agglutination tests, and for beta-lactam
      resistance by real-time PCR. The sequence types (STs) determined by MLST were
      analysed using eburst v3. RESULTS: Eighty-eight out of 191 (46.1 %) H. influenzae
      isolates were BLNAR by PCR; 37 of 61 (60.7 %) from pneumonia; 33 of 68 (48.5 %)
      from AOM and 18 of 62 (29.0 %) from meningitis cases. MLST identified 40 and 44
      STs among isolates from pneumonia and AOM, respectively. BLNAR were found in
      singletons such as ST156 in pneumonia, and ST161 and ST396 in AOM. In contrast,
      eight STs were identified in meningitis, of which seven were genotypically
      closely related, while ST54 was the most frequent (62.9 %), unlike in the MLST
      database registrations, where ST6 predominated. CONCLUSION: Non-typeable H.
      influenzae (NTHi), mostly derived from pneumonia and AOM, were genetically
      diverse, in contrast to the predominance of H. influenzae type b (Hib) among
      meningitis cases. The associations between certain STs and beta-lactam resistance
      among NTHi were confirmed.

PMID- 29595415
TI  - High-throughput sequencing identification and characterization of potentially
      adhesion-related small RNAs in Streptococcus mutans.
AB  - PURPOSE: Adherence capacity is one of the principal virulence factors of
      Streptococcus mutans, and adhesion virulence factors are controlled by small RNAs
      (sRNAs) at the post-transcriptional level in various bacteria. Here, we aimed to
      identify and decipher putative adhesion-related sRNAs in clinical strains of S.
      mutans. METHODOLOGY: RNA deep-sequencing was performed to identify potential
      sRNAs under different adhesion conditions. The expression of sRNAs was analysed
      by quantitative real-time PCR (qRT-PCR), and bioinformatic methods were used to
      predict the functional characteristics of sRNAs. RESULTS: A total of 736
      differentially expressed candidate sRNAs were predicted, and these included 352
      sRNAs located on the antisense to mRNA (AM) and 384 sRNAs in intergenic regions
      (IGRs). The top 7 differentially expressed sRNAs were successfully validated by
      qRT-PCR in UA159, and 2 of these were further confirmed in 100 clinical isolates.
      Moreover, the sequences of two sRNAs were conserved in other Streptococcus
      species, indicating a conserved role in such closely related species. A good
      correlation between the expression of sRNAs and the adhesion of 100 clinical
      strains was observed, which, combined with GO and KEGG, provides a perspective
      for the comprehension of sRNA function annotation. CONCLUSION: This study
      revealed a multitude of novel putative adhesion-related sRNAs in S. mutans and
      contributed to a better understanding of information concerning the
      transcriptional regulation of adhesion in S. mutans.

PMID- 29595418
TI  - Human papillomavirus (HPV) 16 E6 oncoprotein targets the Toll-like receptor
      pathway.
AB  - Cervical cancer is one of the leading causes of death in women worldwide and is
      etiologically linked to human papillomavirus (HPV) infection. Viral early
      proteins E6 and E7 manipulate cellular functions to promote the virus life cycle
      and are essential to the cellular transformation process. The innate immune
      system plays a pivotal role in the natural history of HPV infection. Among the
      various proteins that mediate the innate immune response, Toll-like receptors
      (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and initiate the
      immune response. The objective of this study was to identify HPV E6 protein
      interaction partners in the TLR signalling pathway that may play a role in the
      immune response against HPV. Six TLR pathway proteins were shown to interact with
      HPV16 E6: myeloid differentiation primary response protein (MyD88), TIR domain
      containing adapter molecule 1 (TRIF), interleukin-1 receptor-associated kinase
      like (IRAK) 2, TNF receptor-associated factor (TRAF) 6, I-kappaB kinase beta
      (IKKbeta) and I-kappaB kinase epsilon (IKKepsilon). The interaction site of
      IKKepsilon with E6 is located in the region containing the enzyme catalytic site,
      suggesting an influence of E6 on the activation of IKKepsilon target proteins.
      HPV16 E6 potentiated the activation of NF-kappaB by various TLR pathway members.
      These results suggest that HPV16 has the ability to interfere with components of
      the immune response, contributing to HPV carcinogenesis.

PMID- 29595419
TI  - From the Editors.

PMID- 29595420
TI  - Walking the Path Together: Indigenous Health Data at ICES.
AB  - Indigenous data governance principles assert that Indigenous communities have a
      right to data that identifies their people or communities, and a right to
      determine the use of that data in ways that support Indigenous health and self
      determination. Indigenous-driven use of the databases held at the Institute for
      Clinical Evaluative Sciences (ICES) has resulted in ongoing partnerships between
      ICES and diverse Indigenous organizations and communities. To respond to this
      emerging and complex landscape, ICES has established a team whose goal is to
      support the infrastructure for responding to community-initiated research
      priorities. ICES works closely with Indigenous partners to develop unique data
      governance agreements and supports processes, which ensure that ICES scientists
      must work with Indigenous organizations when conducting research that involves
      Indigenous peoples.

PMID- 29595421
TI  - Opioid-Related Harms in Canada.
AB  - The rise in harms associated with opioids is an issue of increasing public health
      importance in Canada. The Government of Canada recently reported 2,816 apparent
      opioid-related deaths across the country in 2016. Recent 2017 data show that
      deaths involving fentanyl-related opioids have doubled from January to March as
      compared to the same time period in 2016 (Government of Canada 2017). Additional
      measures that provide a better understanding of opioid-related harms, such as
      hospitalizations and emergency department (ED) visits, are a high priority. The
      objective of this study is to present pan-Canadian data on hospitalizations and
      ED visits because of opioid poisoning.

PMID- 29595422
TI  - Open Family Presence Adoption: Role of Patient and Family Advisors.
AB  - The philosophy of patient- and family-centred care is widely being adopted in
      Canada. Critical to this philosophy is the engagement of patients and families as
      full partners in healthcare. Saskatchewan has successfully adopted a provincial
      policy that eliminates restrictive visiting hours in hospitals and other
      healthcare facilities that support partnership with patients and families. This
      article explains the key role that patient and family advisors played in
      identifying the need for change and co-creating the implemented Open Family
      Presence Policy in Saskatchewan. The article outlines the system model, method
      and audit process that supported the policy implementation.

PMID- 29595423
TI  - Cancer Care Ontario's Systematic Symptom Screening Strategy: A Human-Centred
      Design Approach to Exploring System Gaps and Defining Strategies for the Future.
AB  - Cancer patients experience a high symptom burden throughout their illness.
      Quality cancer symptom management has been shown to improve patient quality of
      life and prevent emergency department use. Cancer Care Ontario introduced
      standardized symptom screening in Ontario, using the Edmonton Symptom Assessment
      System (ESAS) to facilitate patient reporting and management of symptoms.
      However, patient symptom information is not always sufficiently addressed. To
      address these gaps, patient and family advisors collaborated with clinicians,
      administrators and health system leaders from across the Province in a Symptom
      Management Summit to share perspectives and co-design context-specific solutions
      to improve care in their region.

PMID- 29595424
TI  - Success Strategies for Linguistically Competent Healthcare: The Magic Bullets and
      Cautionary Tales of the Active Offer of French-Language Health Services in
      Ontario.
AB  - An active offer of French-language health services (FLHS) was introduced in
      several Canadian provinces to help create an environment that will anticipate the
      needs of Francophones in their community and will stimulate the demand for
      services in French. For the active offer to be implemented, changes in how health
      services are organized and managed at both organizational and system levels must
      be introduced. In this perspective paper, we identify several success strategies
      and potential pitfalls with regards to the implementation of the active offer of
      FLHS primarily at the level of healthcare organization. Our recommendations are
      based on a recent health services research study exploring reorganization and
      management strategies for the delivery of the active offer of FLHS in Ontario and
      insights from a focus group with healthcare administrators conducted as part of
      this research. We propose a ";wrap-around strategy" called organizational health
      literacy to help reorient organizational culture and improve management and
      sustainability of the active offer of FLHS. These strategies have relevance for
      advocates and professionals working to promote an active offer of FLHS, including
      healthcare administrators, human resource professionals, quality-improvement
      specialists and others.

PMID- 29595425
TI  - The Healthcare Environment: A Perfect Ecosystem for Growing Shame.
AB  - The expression "shame and blame" has often been used to describe the culture
      within healthcare when a mistake is made. There has been little exploration,
      however, on the shame healthcare professionals experience after a mistake. Based
      on an original grounded theory study on the psychological impact of mistakes on
      health professionals, this article explores why the healthcare environment is a
      perfect ecosystem for growing shame, how individuals are coping or not coping
      with the negative effects of this powerful emotion and what might be done at the
      system, organizational and team level to mitigate these negative effects.

PMID- 29595426
TI  - A Walk in My Shoes: A Mixed-Method Study of the Role of Interprofessional Job
      Shadowing in Shaping Staff Attitudes at a Large Acute Care Hospital in Canada.
AB  - Poor hospital unit culture and staff morale, and dysfunctional multidisciplinary
      cooperation leads to worse patient safety and satisfaction. The Walk in My Shoes
      research project aimed to understand how interprofessional job shadowing impacts
      the attitudes of colleagues. Thirty-three registered nurses at an acute care
      hospital observed the daily work of social workers. Nurses' attitudes towards
      social workers were measured by surveys and interviews. Quantitative data
      indicated a change in nurses' perception of social workers' communication,
      teamwork and autonomy. Qualitative data indicate that job shadowing helped
      participants identify personal misperceptions, provided new understanding of
      roles and gave insight into co-worker job similarities.

PMID- 29595427
TI  - Bundling Care for Cardiac Surgery Patients.
AB  - Patients returning to the community after surgery often experience a disconnect
      when transitioning from hospital to community home care. Many receive little
      organized/planned care following discharge sometimes resulting in unplanned
      expensive care in hospital emergency departments and inpatient readmissions.
      Trillium Health Partners, a large community/teaching hospital, in partnership
      with community care provider Saint Elizabeth Health Care, designed and
      implemented a seamless "bundled care program" for cardiac surgery patients
      extending from hospitalization to 30 days after discharge. With a risk/gain
      sharing model, the bundled care program enabled a novel integrated clinical
      patient care model. This included integrated care coordinators embedded within
      the hospital team, 24/7 patient phone line, integrated medical records and a
      tracking board that enabled performance monitoring and improvement. Evaluation
      results revealed: a 16% reduction in post-operative length of stay; a 38%
      reduction in readmission rates; and a 13% decrease in total system cost per
      patient, together with markers of improved patient experience.

PMID- 29595428
TI  - Using the Time-Driven Activity-Based Costing Model in the Eye Clinic at The
      Hospital for Sick Children: A Case Study and Lessons Learned.
AB  - One of the key challenges to healthcare organizations is the development of
      relevant and accurate cost information. In this paper, we used time-driven
      activity-based costing (TDABC) method to calculate the costs of treating
      individual patients with specific medical conditions over their full cycle of
      care. We discussed how TDABC provides a critical, systematic and data-driven
      approach to estimate costs accurately and dynamically, as well as its potential
      to enable structural and rational cost reduction to bring about a sustainable
      healthcare system.

PMID- 29595429
TI  - Towards a Responsive, Sustainable and Collaborative Model of Care at Toronto's
      Michael Garron Hospital.
AB  - In 2008, Michael Garron Hospital, transformed its approach to care delivery. The
      rationale: to improve quality, increase safety and boost patient and staff
      engagement and satisfaction. The Coordinated Care Team (CCT) model has enabled
      nurses to not only work to their full scopes of practice within a team of
      interprofessional providers and unlicensed staff, but also helped create a
      culture of safety and patient-centredness in a value-driven context. Critics
      suggest a need for more evaluation and evidence of efficacy. This article
      provides a rationale, discussion and evaluation of the CCT model based on data
      curated from implementation to 2016.

PMID- 29595430
TI  - Surveillance Software and Prospective Audit and Feedback Rounds Advance
      Antimicrobial Stewardship at an Acute Care Community Hospital.
AB  - Antimicrobial stewardship is a key strategy to facilitate judicious antimicrobial
      use. Software that can amalgamate prescribing and microbiology information in
      near real-time reporting and track antimicrobial resistance patterns aids timely
      interventions. This article examines the impact of a clinical surveillance
      software used to identify patients for prospective audit and feedback rounds by
      an antimicrobial stewardship team on antibiotic utilization, patient outcomes and
      workload efficiencies at an acute care community hospital. Results from a general
      internal medicine unit show statistically significant reductions in the use of
      broad-spectrum antibiotics and antibiotic expenditures, with no untoward changes
      in key clinical and patient safety outcomes.

PMID- 29595431
TI  - A Technology-Enabled Solution to Manage Referrals to Hospice and Palliative Care
      Beds: The Ottawa SMART System as a Case Study.
AB  - Ottawa has a 31-bed palliative care unit (PCU) and two residential adult hospices
      (total 19 beds). In 2013, we initiated a project to improve the referral and
      triage processes to these beds. Previously, there were two separate paper-based
      systems with duplication, inefficiencies, delays and inappropriate patient
      placements. The multipronged approach included clarifying the respective roles of
      the PCU and hospices, creating a single referral and triage office and developing
      an e-platform. We leveraged technology that was available in the public-funded
      system. This paper describes the development processes, lessons learned, and the
      final system, referred to as System to Manage Access, Referrals and Triage
      (SMART).

PMID- 29595432
TI  - Curious Silences in Healthcare Policy and Research.

PMID- 29595433
TI  - Research on Human Embryos and Reproductive Materials: Revisiting Canadian Law and
      Policy.
AB  - Research involving human embryos and reproductive materials, including certain
      forms of stem cell and genetic research, is a fast-moving area of science with
      demonstrated clinical relevance. Canada's current governance framework for this
      field of research urgently requires review and reconsideration in view of
      emerging applications. Based on a workshop involving ethics, legal, policy,
      scientific and clinical experts, we present a series of recommendations with the
      goal of informing and supporting health policy and decision-making regarding the
      governance of the field. With a pragmatic and principled governance approach,
      Canada can continue its global leadership in this field, as well as advance the
      long-term health and well-being of Canadians.

PMID- 29595434
TI  - Medicine, Body Fluid and Food: The Regulation of Human Donor Milk in Canada.
AB  - The use of peer-to-peer online networks to access both pasteurized and
      unpasteurized human donor milk is increasing in Canada. In the absence of a
      mother's own milk, donor milk is the next best nutrition available for all
      infants in need of supplementation. Limited supply and the cost of pasteurized
      milk puts it out of reach for many. Although milk banks in Canada all operate on
      a non-profit basis, there is a lack of regulatory safeguards regarding for-profit
      operations and private milk exchange. This paper describes regulation of human
      donor milk and identifies gaps putting families at risk.

PMID- 29595435
TI  - Medicare Cost Drivers during the 2004-2014 Health Accord Period in Canada: What
      Is the Evidence?
AB  - As per the Canada Health Act, hospital and physician services (Medicare) are
      covered by the public sector. With the 2004 First Minister's Health Accord
      showcasing a 10-Year Plan to strengthen healthcare in Canada, significant
      investments have been made to improve access to these services. The average
      annual growth rate (AAGR) of spending between 2004 and 2014 was 5.1% for
      hospitals and 6.6% for physicians. The key policy question is whether or not
      these increases were just used to boost unit cost? An accounting approach was
      used to address this issue. Results suggest that for hospitals, wage per hour for
      staff (excluding physicians) accounted for 49% of the AAGR for hospitals (2.5
      percentage points [pp]), while fee increases accounted for 47% of the AAGR for
      physician spending (3.1 pp). However, considering that general inflation was on
      average 1.8% per year, the health premium for physicians represented almost twice
      that for hospital staff.

PMID- 29595436
TI  - The Medical Devices Special Access Program in Canada: A Scoping Study.
AB  - New health technologies enter Canadian healthcare organizations in various ways,
      and understanding them is essential to the development of a pan-Canadian Health
      Technology Management (HTM) Strategy, now a priority of governments across
      Canada. One way is through Health Canada's Medical Devices Special Access Program
      (MDSAP), which permits unlicensed devices to be obtained by healthcare
      professionals. However, the circumstances around and implications of the current
      use of this program are not clear. A scoping literature review was conducted to
      clarify these and identify important roles and issues related to the MDSAP.
      Limited information was found on the MDSAP. Nevertheless, three themes
      demonstrating the roles of the MDSAP in HTM emerged: arbiter in technology
      selection, a route to technology procurement and facilitator of health technology
      innovation. No information suggesting that MDSAP is used to circumvent licensing
      was found. Rather, it enables desired patient outcomes and product
      commercialization.

PMID- 29595437
TI  - Understanding Patient Referral Wait Times for Specialty Care in Ontario: A
      Retrospective Chart Audit.
AB  - CONTEXT: When examining wait times for specialist care, the duration between a
      patient's referral and specialist visit (wait time one) is poorly understood.
      OBJECTIVES: To calculate wait time one in primary care clinics across Ontario
      using chart audit. METHODS: We conducted a retrospective chart audit at five
      Ontario-based primary care clinics in 2014-2015. RESULTS: We analyzed 461
      referrals. Median wait time one for non-urgent and urgent referrals was 79 and 49
      days, respectively. Gastroenterology, obstetrics/gynecology, and ear, nose and
      throat received the most referrals. Wait times were longest for dermatology (112
      days) and shortest for general surgery (32 days). CONCLUSION: Wait times vary
      substantially by referral urgency and specialty type in Ontario. Calculating wait
      time from primary care clinics directly offers new perspectives on wait time one
      and enables clinics to target improvement efforts to best meet patient needs. Our
      findings will be relevant to providers and policy makers interested in
      implementing strategies to reduce wait times.

PMID- 29595438
TI  - Shaping the Future of Patient Experience Measurement in Canadian Healthcare.
AB  - Patients' experiences with healthcare providers can be tumultuous and stressful.
      Focusing on what matters, the experience of care is important to improving
      patients' quality of life. In this issue's lead article, Kuluski and colleagues
      (2017) propose moving beyond setting-based patient experience measures. In doing
      so, the authors emphasize the importance of caregivers and the communities in
      which patients live in improving patients' and caregivers' care experiences. To
      achieve these aims, however, the authors demand a higher level of reflexivity
      from provinces' healthcare funders and providers.

PMID- 29595439
TI  - Experience of Care as a Critical Component of Health System Performance
      Measurement: Recommendations for Moving Forward.
AB  - People's experiences can provide critical guidance on how to better meet their
      quality of life and care needs and deploy resources more appropriately. To
      maximize the utility of experience data and to advance the current debate, we
      present four recommendations: (1) measuring experiences outside the healthcare
      system can provide insight into what needs to change within the healthcare
      system; (2) focusing on patient experience is necessary but insufficient,
      (family) caregiver insights and experiences require attention and can provide
      insight into the needs of the patient; (3) moving from "one time/single sector"
      measurement of experience to iterative, ongoing measurement across sectors better
      reflects the true lived experience of patients (especially those with complex
      care needs) and their caregivers; and (4) embedding measurement within engagement
      capable environments that adequately resource patients, caregivers, and providers
      to work together is required to move from collection to meaningful change.
      Applying these recommendations requires a longer-term vision, shifting from
      provider-centred to person-centred models of care, and a deep understanding of
      the structural, cultural, and normative barriers to measuring care experiences.

PMID- 29595440
TI  - Measuring Patient Experiences: Is It Meaningful and Actionable?
AB  - Performance measurement must be meaningful to those being asked to contribute
      data and to the clinicians who are collecting the information. It must be
      actionable if performance measurement and reporting is to influence health system
      transformation. To date, measuring patient experiences in all parts of the
      healthcare system in Canada lags behind other countries. More attention needs to
      be paid to capturing patients with complex intersecting health and social
      problems that result from inequitable distribution of wealth and/or underlying
      structural inequities related to systemic issues such as racism and
      discrimination, colonialism and patriarchy. Efforts to better capture the
      experiences of patients who do not regularly access care and who speak English or
      French as a second language are also needed. Before investing heavily into
      collecting patient experience data as part of a performance measurement system
      the following ought to be considered: (1) ensuring value for and buy-in from
      clinicians who are being asked to collect the data and/or act on the results; (2)
      investment in the infrastructure to administer iterative, cost-effective
      patient/family experience data collection, analysis and reporting (e.g.,
      automated software tools) and (3) incorporating practice support (e.g.,
      facilitation) and health system opportunities to integrate the findings from
      patient experience surveys into policy and practice. Investment into the
      infrastructure of measuring, reporting and engaging clinicians in improving
      practice is needed for patient/caregiver experiences to be acted upon.

PMID- 29595441
TI  - Health System Performance Measurement: A UK Perspective.
AB  - In response to the lead article by Kuluski et al. (2017), this commentary draws
      on UK debates around the quality of healthcare and on the author's personal
      experience training as a social worker. Judging whether a service has "worked"
      has to involve understanding what a good outcome would be for the person
      receiving it. While carers provide important insights here, the "user" may have a
      different view, and reconciling different perspectives can be challenging.
      Although individual services may have fulfilled their part of the process, it is
      important to look at the person's overall experience (although this is difficult
      to achieve in practice). There is also no point measuring patient experience if
      we are not prepared to really listen to the feedback we receive. Moving forward,
      the UK's personalization agenda - which focuses on giving people greater choice
      and control - may enhance the aims of Kuluski et al.'s work.

PMID- 29595442
TI  - Reacting to Patient Experience Results - How Can We Be Proactive?
AB  - Among the recommendations raised in the lead paper (Kuluski et al. 2017) for
      optimizing the utility of patient experience data are several important questions
      about the nature of person-centred care, the engagement of patients and
      caregivers in evaluating care and the need to address barriers to measurement.
      This commentary focuses on the concept that common approaches to measuring
      patient experience are reactive by design. To truly enhance our patients'
      experience, we must first connect with patients to understand what they want from
      their care experience. In addition, this paper explores the practicality of using
      patient experience data for quality improvement, particularly if there is a shift
      towards measuring experience across the system of care.

PMID- 29595443
TI  - Engagement-Capable Environments - No Less Challenging than other Large System
      Changes.
AB  - Kuluski et al.'s (2017) argument for including a more advanced form of health
      system performance management centred on "the experience of care," raises the
      major challenge of creating and sustaining engagement-capable environments. Here
      I briefly address frameworks that may be useful in meeting this challenge -
      Complex Adaptive Systems, Innovation Diffusion, Whole System Change. I also offer
      a personal perspective drawn from a successful citizen engagement experience,
      concluding with a perspective on the numerous challenges we have or are in the
      process of overcoming compared to the challenges of engagement-capable
      environments.

PMID- 29595444
TI  - More than just Measurement.
AB  - I have reviewed with pleasure the article by Kuluski et al. (2017) who posit that
      measures of patient experience are required to more effectively guide healthcare
      reform. While I am generally in support of the original paper, I argue in this
      commentary that: (1) measuring patient engagement experience should not be done
      in isolation from broader change management processes; (2) care must be taken to
      ensure that measures of patient experience are developed with rigor and do not
      further complicate the already vast performance metrics literature and, (3) any
      revised set of performance metrics requires ongoing evaluation, to help ensure
      its optimal value.

PMID- 29595445
TI  - Experience of Care - Furthering the Patient Experience Agenda.
AB  - The measurement of the patient experience is a global movement that has caught
      the attention of healthcare reformers. The use of patient experience data to
      ameliorate healthcare practice is promising, although standardization in what,
      where, how and whose experience is measured does not yet exist. To truly further
      the patient experience agenda, there needs to be adoption at the system, regional
      and local level to help promote, inspire and lead to sustainable change.
      Caregiver insight into the patient experience should be leveraged to learn what
      is important to patients and extract more useful data, as they are often present
      during transitions in care that span across the continuum. Embracing the voice of
      the patient as part of the process to improve quality, outcomes and experience
      will no doubt lead to impactful change and better care.

PMID- 29595446
TI  - Rethinking Healthcare Performance Evaluation Systems towards the People
      Centredness Approach: Their Pathways, their Experience, their Evaluation.
AB  - Patient experience should be the starting point to achieve a high quality of
      care. Coherently, healthcare performance evaluation systems, driving the change
      in line with the main strategic goals, should be designed considering the patient
      perspective. Instead, they are traditionally defined according to the healthcare
      service provider's point of view. Consequently, they reproduce a "silo-vision"
      characterized by a clear separation of responsibilities limited to a specific
      setting of care or to a single organization. This commentary discusses the
      importance of using patient-reported measures together with indicators based on
      administrative data to evaluate cross-setting healthcare services within a
      multidimensional healthcare performance evaluation system. The experience of the
      Tuscany regional healthcare Performance Measurement System (PMS), implemented
      more than 10 years ago and in continuous evolution, represents an innovative
      example of how to measure the quality of the whole care pathway including patient
      experience. This new approach is based on a systematic, systemic and standardized
      collection of patient-reported experience measures in several healthcare pathways
      and evaluating them using a coherent graphical representation. Targets,
      incentives and other managerial tools are fixed, overcoming organizational
      boundaries and integrating the patient point of view with the goal of moving the
      healthcare system towards a patient-centredness approach to care.

PMID- 29595447
TI  - Putting Performance Measurement Recommendations into Practice: Building on
      Current Practices.
AB  - Improving performance measurement within the Canadian healthcare system is
      proving to be challenging despite advances in evidence-informed care and best
      practices for healthcare delivery. Perhaps what is most challenging is the need
      to meet requirements to measure what most Canadians hold dear - being seen as a
      person during a healthcare encounter. Measures of healthcare delivery have
      typically been developed to capture patient satisfaction during isolated
      healthcare encounters. Such measures simply do not get to the essence of what
      matters to patients and their families. This paper outlines a response to the
      paper by Kuluski and colleagues (2017) that calls for a thorough review of the
      way data are currently captured on patients' experiences with healthcare. Using
      geriatric medicine as a context, the authors highlight elements of our current
      care delivery models that must be preserved, modified or created to allow
      patients and families to play a larger role in improving our healthcare system.

PMID- 29595448
TI  - From Volumes to Valued Experiences: Measurement and the Challenge before Us.
AB  - We are grateful for the thoughtful discussion and ideas put forth in this issue
      on the measurement of healthcare experiences. Our colleagues, who span multiple
      jurisdictions across Canada and internationally, agree that we need to do a
      better job at engaging patients and families in their care and measuring their
      experiences across health services and sectors. In this response paper, we
      reflect on three core content areas that were identified across the eight papers
      in this issue: the role of context and engagement-capable environments;
      approaches to improve the measurement of experience and acting on results; and
      challenges that must be attended to in our quest to make our healthcare systems
      work better.

PMID- 29595449
TI  - Routine low-dose continuous or nocturnal oxygen for people with acute stroke:
      three-arm Stroke Oxygen Supplementation RCT.
AB  - BACKGROUND: Stroke is a major cause of death and disability worldwide. Hypoxia is
      common after stroke and is associated with worse outcomes. Oxygen supplementation
      could prevent hypoxia and secondary brain damage. OBJECTIVES: (1) To assess
      whether or not routine low-dose oxygen supplementation in patients with acute
      stroke improves outcome compared with no oxygen; and (2) to assess whether or not
      oxygen given at night only, when oxygen saturation is most likely to be low, is
      more effective than continuous supplementation. DESIGN: Multicentre, prospective,
      randomised, open, blinded-end point trial. SETTING: Secondary care hospitals with
      acute stroke wards. PARTICIPANTS: Adult stroke patients within 24 hours of
      hospital admission and 48 hours of stroke onset, without definite indications for
      or contraindications to oxygen or a life-threatening condition other than stroke.
      INTERVENTIONS: Allocated by web-based minimised randomisation to: (1) continuous
      oxygen: oxygen via nasal cannula continuously (day and night) for 72 hours after
      randomisation at a flow rate of 3 l/minute if baseline oxygen saturation was <=
      93% or 2 l/minute if > 93%; (2) nocturnal oxygen: oxygen via nasal cannula
      overnight (21:00-07:00) for three consecutive nights. The flow rate was the same
      as the continuous oxygen group; and (3) control: no routine oxygen
      supplementation unless required for reasons other than stroke. MAIN OUTCOME
      MEASURES: Primary outcome: disability assessed by the modified Rankin Scale (mRS)
      at 3 months by postal questionnaire (participant aware, assessor blinded).
      Secondary outcomes at 7 days: neurological improvement, National Institutes of
      Health Stroke Scale (NIHSS), mortality, and the highest and lowest oxygen
      saturations within the first 72 hours. Secondary outcomes at 3, 6, and 12 months:
      mortality, independence, current living arrangements, Barthel Index, quality of
      life (European Quality of Life-5 Dimensions, three levels) and Nottingham
      Extended Activities of Daily Living scale by postal questionnaire. RESULTS: In
      total, 8003 patients were recruited between 24 April 2008 and 17 June 2013 from
      136 hospitals in the UK [continuous, n = 2668; nocturnal, n = 2667; control, n =
      2668; mean age 72 years (standard deviation 13 years); 4398 (55%) males]. All
      prognostic factors and baseline characteristics were well matched across the
      groups. Eighty-two per cent had ischaemic strokes. At baseline the median Glasgow
      Coma Scale score was 15 (interquartile range 15-15) and the mean and median NIHSS
      scores were 7 and 5 (range 0-34), respectively. The mean oxygen saturation at
      randomisation was 96.6% in the continuous and nocturnal oxygen groups and 96.7%
      in the control group. Primary outcome: oxygen supplementation did not reduce
      disability in either the continuous or the nocturnal oxygen groups. The
      unadjusted odds ratio for a better outcome (lower mRS) was 0.97 [95% confidence
      interval (CI) 0.89 to 1.05; p = 0.5] for the combined oxygen groups (both
      continuous and nocturnal together) (n = 5152) versus the control (n = 2567) and
      1.03 (95% CI 0.93 to 1.13; p = 0.6) for continuous versus nocturnal oxygen.
      Secondary outcomes: oxygen supplementation significantly increased oxygen
      saturation, but did not affect any of the other secondary outcomes. LIMITATIONS:
      Severely hypoxic patients were not included. CONCLUSIONS: Routine low-dose oxygen
      supplementation in stroke patients who are not severely hypoxic is safe, but does
      not improve outcome after stroke. FUTURE WORK: To investigate the causes of
      hypoxia and develop methods of prevention. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN52416964 and European Union Drug Regulating Authorities Clinical
      Trials (EudraCT) number 2006-003479-11. FUNDING DETAILS: This project was funded
      by the National Institute for Health Research (NIHR) Research for Patient Benefit
      and Health Technology Assessment programmes and will be published in full in
      Health Technology Assessment; Vol. 22, No. 14. See the NIHR Journals Library
      website for further project information.

PMID- 29595450
TI  - [Analysis of the correlation between E2F3 expression and the number of tumor
      infiltrating CD8+T cells in invasive bladder cancer tissues].
AB  - Objective To investigate the expression of E2F transcription factor 3 (E2F3) and
      the infiltration of CD8+T cells in bladder cancer tissues and their correlations
      with the malignant biological behaviors of bladder cancer. Methods The expression
      level of E2F3 and the infiltration characteristics of CD8+T cells in 110 cases of
      bladder cancer tissues with different histological stage and grade as well as in
      the corresponding normal bladder tissues were detected by immunohistochemistry.
      Western blot analysis was used to detect E2F3 and CD8 protein levels in 82 cases
      of bladder cancer tissues and the corresponding normal bladder tissues, and then
      the correlation between E2F3 expression and CD8+ T cell infiltration was analyzed
      statistically by linear correlation analysis. Results The expression of E2F3 was
      higher in the bladder cancer tissues than in the normal bladder tissues. The
      expression level of E2F3 increased gradually with the increase of tumor
      histological stage and grade, while the number of tumor-infiltrating CD8+T cells
      decreased gradually in the corresponding tumors, and the number of tumor
      infiltrating CD8+T cells in E2F3 high expression group was significantly lower
      than that in E2F3 low expression group. Both the rate of E2F3 positive expression
      and the decrease in the number of tumor-infiltrating CD8+T cells were closely
      related to tumor clinical invasive indicators, such as tumor histological stage,
      grade, tumor size, lymph node metastasis or distant metastasis. Linear
      correlation analysis indicated that the number of tumor-infiltrating CD8+T cells
      was negatively correlated with the expression of E2F3. Survival analysis revealed
      that the prognosis of patients with high E2F3 expression was worse after
      operation within 5 years. Conclusion The expression level of E2F3 in bladder
      cancer is closely related to tumor invasiveness, and is negatively correlated
      with the number of tumor-infiltrating CD8+T cells.

PMID- 29595452
TI  - [Overexpression of miR-519d-3p inhibits the proliferation of DU-145 prostate
      cancer cells by reducing TRAF4].
AB  - Objective To observe the effect of microRNA-519d-3p (miR-519d-3p) on the
      proliferation of prostate cancer cells and explore the possible molecular
      mechanism. Methods The expression level of miR-519d-3p in PC-3, DU-145, 22RV1, PC
      3M, LNCaP human prostate cancer cells and RWPE-1 human normal prostate epithelial
      cells was detected by real-time quantitative PCR. miR-519d-3p mimics or negative
      control microRNAs (miR-NC) was transfected into the prostate cancer cells with
      the lowest level of miR-519d-3p expression. Transfection efficiency was examined.
      The effect of miR-519d-3p on the cell cycle of prostate cancer was detected by
      flow cytometry. MTT assay and plate clone formation assay were used to detect its
      effect on the proliferation of prostate cancer cells. Bioinformatics software was
      used to predict and dual luciferase reporter assay was used to validate the
      target gene of miR-519d-3p. Real-time quantitative PCR was used to detect the
      expression of miR-519d-3p target gene. Western blot analysis was used to detect
      the expression of target gene protein and downstream protein. Results The
      expression of miR-519d-3p in normal prostate epithelial cells was significantly
      higher than that in prostate cancer cells, and the lowest was found in DU-145
      cells. After transfected with miR-519d-3p mimics, the expression level of miR
      519d-3p in DU-145 cells increased significantly. Bioinformatics prediction and
      dual luciferase reporter gene confirmed that tumor necrosis factor receptor
      associated factor 4 (TRAF4) was the target gene of miR-519d-3p. Overexpression of
      miR-519d-3p significantly reduced the expression of TRAF4 gene and its downstream
      TGF-beta signaling pathway proteins in the prostate cancer cells. Conclusion The
      expression of miR-519d-3p is down-regulated in prostate cancer cells.
      Overexpression of miR-519d-3p can inhibit the proliferation of prostate cancer
      cells. The possible mechanism is that miR-519d-3p inhibits the expression of
      TRAF4.

PMID- 29595451
TI  - [LRIG1 promotes the apoptosis of pituitary tumor cells induced by cisplatin].
AB  - Objective To investigate the expression of leucine rich repeats and
      immunoglobulin like domains 1 (LRIG1) in the tumor tissues of human pituitary
      tumor, and the effects of LRIG1 over-expression on the proliferation and
      apoptosis of human pituitary tumor cells induced by cisplatin (DDP). Methods The
      expression of LRIG1 in the tumor tissues and adjacent tissues of 45 cases with
      pituitary tumor was detected by immunohistochemistry, and the correlations
      between the positive expression of LRIG1 and the clinicopathological data of the
      patients were analyzed. In addition, the isolated human pituitary tumor cells
      were selected. The LRIG1 gene over-expression plasmid pEGFP-N1-LRIG1 was
      transfected into the cells by liposome-mediated gene transfection. The cells
      transfected with LRIG1 were screened, and meanwhile, the cells transfected with
      empty plasmid pEGFP-N1 were selected as a control group. The cells of the two
      groups were induced by 20 g/mL DDP, and 48 hours later, the cell apoptosis was
      detected by flow cytometry; the proliferation capacity was tested by plate
      cloning experiment; and the relative expressions of apoptosis-related proteins
      Bax, caspase-3 and Bcl2 in the cells were examined by Western blot analysis.
      Results LRIG1 in the tumor tissues of pituitary tumor was obviously lower than
      that of the adjacent tissues, and LRIG1 was significantly reduced in the invasive
      tumor tissues. Compared with the control group, after LRIG1 was over-expressed,
      the cell apoptosis rate significantly increased, the cell proliferation
      significantly decreased, and the levels of Bax and caspase-3 increased as well,
      while the level of Bcl2 decreased remarkably. Conclusion Over-expression of LRIG1
      increases the apoptosis and inhibits the proliferation of human pituitary tumor
      cells induced by DDP.

PMID- 29595453
TI  - [Differential expression and correlation to cytokine expressions of FFAR4 in
      peritoneal and alveolar macrophages].
AB  - Objective To investigate the expression level of free fatty acid receptor 4
      (FFAR4) and its correlation with cytokine expressions in peritoneal macrophages
      and alveolar macrophages. Methods Peritoneal macrophages and alveolar macrophages
      were purified and collected using flow cytometry from adult BALB/c mice. Real
      time quantitative PCR was used to measure mRNA expression levels. The correlation
      between FFAR4 expression level and cytokine expression levels was analyzed using
      linear regression. Results The expression levels of FFAR4, interleukin-1 (IL-1)
      and tumor necrosis factor-alpha (TNF-alpha) were significantly higher in the
      alveolar macrophages than in the peritoneal macrophages. In contrast, the
      expression levels of IL-10 and IL-6 were significantly lower in the alveolar
      macrophages than in the peritoneal macrophages. In the peritoneal macrophages,
      FFAR4 expression was positively correlated to the mRNA expressions of IL-10, IL-6
      and TNF-alpha, but negatively correlated to IL-1 mRNA expression. In the alveolar
      macrophages, FFAR4 expression was positively correlated to the mRNA expressions
      of IL-1, IL-6 and TNF-alpha, but negatively correlated to IL-10 mRNA expression.
      Conclusion FFAR4 is differentially expressed and correlated to cytokine
      expressions in peritoneal macrophages and alveolar macrophages from BALB/c mice.

PMID- 29595454
TI  - [Knockdown of dopamine receptor D2 upregulates the expression of adiogenic genes
      in mouse primary mesencephalic neurons].
AB  - Objective To study the effects of dopamine receptor D2 (DRD2) on the adipogenesis
      genes in mouse primary mesencephalic neurons. Methods The lentiviral vectors
      which expressed specific shRNA targeting DRD2 were constructed to decrease DRD2
      expression in mouse primary mesencephalic neurons. High throughput sequencing
      (HTS) analysis was used to investigate gene expression changes between the DRD2
      knock-down group and the negative control group. Real-time quantitative PCR (qRT
      PCR) and Western blot analysis were applied to verify the differently expressed
      genes. Fatty acids were measured by fatty acid detection kit. Results DRD2
      expression was effectively down-regulated in mouse primary mesencephalic neurons
      by lentiviral vectors. HTS revealed adipogenesis genes were significantly up
      regulated after DRD2 down-regulation, mainly including delta(14)-sterol
      reductase, acetyl-coenzyme A synthetase, insulin-induced gene 1 protein and
      especially stearoyl-coenzyme A desaturase 1 (SCD1, 4-fold upregulated). The qRT
      PCR and Western blot analysis verified that SCD1 was upregulated 2.6 folds and 2
      folds respectively by lentiviral DRD2-shRNA vectors. Moreover, the SCD1-related
      free fatty acids were significantly more increased than the negative control
      group. Conclusion DRD2 in primary mesencephalic neurons had a significant
      regulative effect on the adipogenesis genes. The up-regulation of SCD1 can
      accelerate the conversion of saturated fatty acids to monounsaturated fatty acids
      and prevent the damage of lipid toxicity to cells.

PMID- 29595455
TI  - [Mechanism of alpha-lipoic acid promoting iron efflux in substantia nigra cells
      of Parkinson's disease rats].
AB  - Objective To observe the effect of alpha-lipoic acid (alpha-LA) on the
      expressions of iron regulatory protein 2 (IRP2) and ferroportin1 (FP1) in
      substantia nigra of rats with Parkinson's disease (PD) and explore the mechanism
      by which alpha-LA regulates iron efflux in substantia nigra cells of PD rat
      models. Methods Sixty healthy male SD rats were randomly divided into a sham
      group (n=15) and a model group (n=45). To establish the PD model, the rats of the
      model group were injected with 6-hydroxydopamine (6-OHDA) into their right
      striatum by the stereotactic technique, and the sham operation group was injected
      with the same dose of normal saline. Four weeks later, 30 model rats were
      randomly picked and divided into a PD model group (n=15) and a PD treatment group
      (n=15). The PD treatment group was intraperitoneally injected with alpha-LA (50
      mg/kg) daily for 2 weeks, and the PD model group was given the same dose of
      saline. After 14 days of treatment, the left forelimb use rate was tested by
      cylinder test. The right middle cerebral substantia nigra was taken from each
      group, and the expression and distribution of tyrosine hydroxylase (TH) was
      detected by immunohistochemical staining; the number of iron positive cells was
      determined by Prussian blue staining; and the levels of IRP2 and FP1 were
      examined by Western blotting. Results Compared with the sham operation group, the
      left forelimb use rate of the PD model group was significantly reduced. The
      number of TH positive cells significantly decreased, and the number of iron
      positive cells in the substantia nigra significantly increased. The level of IRP2
      significantly increased, and the level of FP1 decreased remarkably. Compared with
      PD model group, the left forelimb use rate of the PD treatment group was
      significantly raised. The number of TH positive cells was significantly elevated,
      and the number of iron positive cells in the substantia nigra was significantly
      reduced. The IRP2 level decreased and the FP1 level increased. Conclusion By
      decreasing the IRP2 level and via the IRP2/IRE pathway, alpha-LA can increase FP1
      level, promote the outflow of iron ions from cells, and reduce iron deposition in
      the substantia nigra of PD model rats, thereby alleviating brain injury in PD
      rats induced by 6-OHDA.

PMID- 29595456
TI  - [Improvement and the mechanism of cardiac function by knockdown of ADAM10 in
      adriamycin-induced cardiomyopathy rats].
AB  - Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in
      shedding neural cadherin (N-cadherin) and develop an approach to interfere the
      process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM)
      rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of
      the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and
      contractile function were observed by HE staining and color Doppler
      echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1)
      were detected by Western blotting and immunohistochemistry. Results In the in
      vivo experiment, a large amount of fluorescence was seen in the isolated primary
      cardiomyocytes, which indicated that the transfection in the rat model was
      successful. In the treatment group, the morphology of cardiomyocytes and function
      of the heart were evidently improved, N-cadherin protein expression was
      remarkably up-regulated and CTF1 protein was obviously down-regulated compared
      with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin
      expression and decreases CTF1 expression, thus improves cardiac function in the
      rat model of ACM.

PMID- 29595457
TI  - [Neurotrophin-3 enhances the osteogenesis ability of human bone marrow
      mesenchymal stem cells stimulated by lipopolysaccharide].
AB  - Objective To investigate the protective effect of neurotrophin-3 (NT-3) on human
      bone marrow mesenchymal stem cells (hBMSCs) and its ability to promote the
      differentiation of hBMSCs into osteoblasts in the inflammatory environment.
      Methods The cell inflammation model was established by lipopolysaccharide (LPS).
      The hBMSCs without any stimulation was defined as the inflammatory control group;
      the hBMSCs stimulated by 100 ng/mL human NT-3 recombinant protein as the NT-3
      group; the hBMSCs stimulated by 100 mmol/L pyrvinium pamoate (PP) for 12 hours
      and then stimulated by 100 ng/mL human NT-3 recombinant protein as the Wnt
      inhibitor group; the normal cultured hBMSCs as the normal control group. We
      performed the experiment of osteoblast induction on all groups. CCK-8 assay was
      used to detect the proliferation of hBMSCs; the fluorescein isothiocyanate
      labeled annexin V/propidium iodide (Annexin V-FITC/PI) double labeling combined
      with flow cytometry was used to detect the apoptosis of hBMSCs; ELISA was used to
      detect the protein levels of runt-related transcription factor 2 (RUNX2) protein
      and alkaline phosphatase (ALP); and the alizarin red staining experiment was
      conducted to detect the ability of calcium nodule formation. Results Compared
      with the inflammatory control group, the proliferative activity of hBMSCs in NT-3
      group significantly increased, the apoptosis obviously decreased, and the
      contents of RUNX2 and ALP, as well as the intensity of alizarin red staining in
      NT-3 group evidently rose. Compared with the NT-3 group, the proliferative
      activity of hBMSCs in the Wnt inhibitor group was inhibited, the cell apoptosis
      was promoted, and the contents of RUNX2 and ALP, as well as the intensity of
      alizarin red staining in the Wnt inhibitor group were reduced remarkably.
      Conclusion NT-3 can protect hBMSCs from anti-inflammatory damage and promote the
      differentiation of hBMSCs into osteoblasts.

PMID- 29595458
TI  - [Nucleocytoplasmic translocation of ING5 protein in breast cancer and its
      correlation with poor clinicopathological characteristics of breast cancer].
AB  - Objective To investigate the nucleocytoplasmic translocation of inhibitor of
      growth family member 5 (ING5) gene in human breast cancer and the negative
      correlation between the nuclear high expression of ING5 protein and the
      clinicopathological characteristics of breast cancer. Methods We collected 260
      cases of clinical primary breast cancer, 55 cases of metastatic cancer in lymph
      node, 61 cases of breast fibroadenoma, 110 cases of adenomatosis, and 91 cases of
      para-cancerous tissues. With the tissue microarrays, we detected ING5 expression
      in the nucleus and cytoplasm through immunohistochemistry, and statistically
      analyzed the correlations of nuclear and cytoplasmic ING5 expression with the
      clinicopathological characteristics of breast cancer. Results The expression of
      nuclear ING5 in the para-cancerous tissues was obviously higher than that in the
      fibroadenoma, adenomatosis and primary breast cancer; it was higher in the
      adenomatosis than in the primary breast cancer, and higher in the primary breast
      cancer than in the metastatic cancer in lymph node. The cytoplasmic ING5
      expression in the para-carcinoma tissue was higher than that in the fibroadenoma,
      adenomatosis and primary breast cancer. These data suggested the
      nucleocytoplasmic translocation of ING5 protein in breast cancer. Moreover,
      nuclear ING5 high expression was negatively correlated with distant metastasis
      and positively with P53 expression, while cytoplasmic ING5 high expression was
      positively correlated with tumor size and estrogen receptor expression. The
      cytoplasm ING5 expression of triple-negative breast cancer was lower than that in
      the non-triple-negative breast cancer. Conclusion Nucleocytoplasmic translocation
      of ING5 protein occurs in breast cancer, and the high expression of nuclear ING5
      is inversely related to some poor clinicopathological behaviors of breast cancer.

PMID- 29595459
TI  - [Pseudolaric acid B induces G2/M arrest and inhibits invasion and migration in
      HepG2 hepatoma cells].
AB  - Objective To investigate the mechanisms of pseudolaric acid B (PAB) blocks cell
      cycle and inhibits invasion and migration in human hepatoma HepG2 cells. Methods
      The proliferation effect of PAB on HepG2 cells was evaluated by MTT assay. The
      effect of PAB on the cell cycle of HepG2 cells was analyzed by flow cytometry.
      Immunofluorescence cytochemical staining was applied to observe the effect of PAB
      on the alpha-tubulin polymerization and expression in HepG2 cells. TranswellTM
      chamber invasion assay and wound healing assay were performed to detect the
      influence of PAB on the migration and invasion ability of HepG2 cells. Western
      blotting was used to determine the expressions of alpha-tubulin, E-cadherin and
      MMP-9 in HepG2 cells after treated with PAB. Results PAB inhibited the
      proliferation of HepG2 cells in a dose-dependent manner and blocked the cell
      cycle in G2/M phase. PAB significantly changed the polymerization and decreased
      the expression of alpha-tubulin. The capacities of invasion and migration of
      HepG2 cells treated by PAB were significantly depressed. The protein levels of
      alpha-tubulin and MMP-9 decreased while the E-cadherin protein level increased.
      Conclusion PAB can inhibits the proliferation of HepG2 cells by down-regulating
      the expression of alpha-tubulin and influencing its polymerization, arresting
      HepG2 cells in G2/M phase. Meanwhile, PAB also can inhibit the invasion and
      migration of HepG2 cells by lowering cytoskeleton alpha-tubulin and MMP-9, and
      increasing E-cadherin.

PMID- 29595460
TI  - [Distribution of Rh blood group in 51 283 cases of inpatients and voluntary blood
      donors].
AB  - Objective To investigate the distribution characteristics of Rh blood group in 51
      283 cases of inpatients and voluntary blood donors. Methods Micro-column gel test
      was used to detect RhD, RhE, Rhe, RhC, Rhc antigen in 31 818 cases of
      hospitalized patients and 19 465 cases of voluntary blood donors. Results There
      were significant differences in Rh blood type distribution between inpatients and
      voluntary blood donors. The mainly phenotype of Rh blood group in the inpatients
      were DCCee (41.64%) and DCcEe (36.58%), and Rh blood type in voluntary blood
      donors were DCCee (41.11%) and DCcEe (37.11%). There were noticeable differences
      in Rh blood group and ABO phenotype between inpatients and voluntary blood
      donors. The mainly phenotype of the RhD positive patients were CcEe (36.58%) and
      CCee (41.64%). However, the mainly phenotype of RhD negative patients were ccee
      (54.30%) and Ccee (30.86%). Additionally, obvious difference of Rh blood group
      was seen between patients in haematology department and all patients. The
      voluntary blood donors from different areas including Hefei, Guangzhou, Nanning
      and Xi'an showed significant different Rh blood group distribution. On the
      contrary, no obvious difference of Rh blood group was found between Xianyang and
      Xi'an. Conclusion The differences of Rh blood group distribution have been found
      in different populations, departments and areas, which make it extremely
      important to detect Rh blood group in clinical transfusion.

PMID- 29595462
TI  - CMS Opens Window for BPCI Advanced but Target Prices Are Still Behind the
      Curtains.
AB  - Medicare's new bundled payments program is expected to be popular, despite
      unanswered questions about the target prices for the episodes, risk adjustment,
      and use of quality data. Until CMS releases more detail on pricing targets and
      other not-so-trivial nuances, providers who jump in may be taking a leap of
      faith.

PMID- 29595461
TI  - Harvard Pilgrim's Patrick Cahill Tries To Make Sense of It All.
AB  - The 40-year-old vice president of regional markets for eastern Massachusetts
      wants enrollees and, especially, employers to know that there will continue to be
      a lot of public policy change as the ACA evolves. His course? Keep strengthening
      ties with providers.

PMID- 29595463
TI  - When Value Is in the Eye Of the Patient.
AB  - Physicians and their charges have different ideas about what makes for good
      cancer care. Patient surveys help, but they need to be handled right.

PMID- 29595464
TI  - Purchasers to Insurers: Standardize Your ACO Measures.
AB  - Building on a similar effort in California, Catalyst for Payment Reform is
      proposing a standardized set of 50 ACO measures. A timely development. In the
      first quarter of last year, an estimated 19.1 million lives were covered by 715
      commercial ACOs, compared with 17.2 million lives a year earlier.

PMID- 29595465
TI  - A Conversation With Mai Pham, MD. Payment Innovation at Anthem: Downside Risk
      Will Be Rewarded.
AB  - The insurer's vice president of provider alignment solutions says: "We're going
      to start to signal to providers that if you are going to stay an upside-only
      arrangement, we're not going to give you free money forever in the form of the
      care-coordination fees that we've been paying out. They're not an entitlement."

PMID- 29595466
TI  - Real-World Evidence Not Quite Believable Enough.
AB  - In theory, this approach could help untangle some knotty cost and quality
      concerns about medications as they move from clinical trials and into clinical
      use. But there's a credibility issue: The perception that much of the research is
      biased and that the studies are designed so the results serve the interests of
      the sponsors.

PMID- 29595467
TI  - Fall Prevention Hits Stumbling Blocks.
AB  - Implementation of efforts to screen older people for fall risk-and to intervene
      before falls occur-have been scattershot at best. Ongoing studies of fall
      prevention called STRIDE (Strategies to Reduce Injuries and Develop Confidence in
      Elders) might change that. The studies look at whether clinicians can implement a
      fall-prevention program across rural, urban, and suburban treatment settings.

PMID- 29595468
TI  - The CVS Effect on American Health Insurance.
AB  - Once they have the right platforms in place, insurers can layer on predictive
      analytics, digital medical records, and other innovations that promise to make
      health care costs more manageable-and in the process make health insurers more
      competitive with the likes of CVS and maybe, eventually, Amazon.

PMID- 29595469
TI  - Assessing Provider Partnerships For Accountable Care Organizations.
AB  - PURPOSE: Understand current provider approaches to the evaluation of various
      partnerships under accountable care contracts and create a framework to help
      accountable care organizations (ACOs) better assess their partnerships. DESIGN:
      Study included (1) an in-depth literature review of materials describing high
      value health care organizations as a foundation for draft framework development,
      (2) an expert panel convened to evaluate the framework and help prioritize
      provider types to evaluate, and (3) interviews with representatives of ACOs and
      entities representing various types of health care providers. METHODOLOGY:
      Authors created a draft partnership framework derived from the literature review
      for expert panel feedback. An updated draft framework was then shared with active
      ACO leaders prior to qualitative interviews. All interviews were transcribed and
      coded using a mixed-methods analysis platform. RESULTS: We found little research
      that took a comprehensive view of health care provider competencies and
      characteristics and by extension few resources to help ACOs fill competency gaps
      through partnerships. The ACOs interviewed were all actively engaged in provider
      partnerships and were learning and establishing best practices for provider
      partnerships. CONCLUSIONS: Accountable care offers incentives for entities to
      improve the cost and quality of health care. To accomplish this in an effective
      way, ACOs must recognize the needs of their assigned populations and work to
      provide comprehensive care management across the spectrum of provider types.
      Accomplishing this will also require ACOs to create novel partnership
      arrangements and learn how to manage populations most effectively. ACOs need a
      framework for evaluating potential partners that will help risk-bearing providers
      establish the partnerships that will enable them to achieve their goals. This
      paper makes specific recommendations on how state and federal policy could
      facilitate better and more effective provider partnerships.

PMID- 29595470
TI  - A transformation from temporal to ensemble coding in a model of piriform cortex.
AB  - Different coding strategies are used to represent odor information at various
      stages of the mammalian olfactory system. A temporal latency code represents odor
      identity in olfactory bulb (OB), but this temporal information is discarded in
      piriform cortex (PCx) where odor identity is instead encoded through ensemble
      membership. We developed a spiking PCx network model to understand how this
      transformation is implemented. In the model, the impact of OB inputs activated
      earliest after inhalation is amplified within PCx by diffuse recurrent collateral
      excitation, which then recruits strong, sustained feedback inhibition that
      suppresses the impact of later-responding glomeruli. We model increasing odor
      concentrations by decreasing glomerulus onset latencies while preserving their
      activation sequences. This produces a multiplexed cortical odor code in which
      activated ensembles are robust to concentration changes while concentration
      information is encoded through population synchrony. Our model demonstrates how
      PCx circuitry can implement multiplexed ensemble-identity/temporal-concentration
      odor coding.

PMID- 29595471
TI  - Live cell-lineage tracing and machine learning reveal patterns of organ
      regeneration.
AB  - Despite the intrinsically stochastic nature of damage, sensory organs
      recapitulate normal architecture during repair to maintain function. Here we
      present a quantitative approach that combines live cell-lineage tracing and
      multifactorial classification by machine learning to reveal how cell identity and
      localization are coordinated during organ regeneration. We use the superficial
      neuromasts in larval zebrafish, which contain three cell classes organized in
      radial symmetry and a single planar-polarity axis. Visualization of cell-fate
      transitions at high temporal resolution shows that neuromasts regenerate
      isotropically to recover geometric order, proportions and polarity with
      exceptional accuracy. We identify mediolateral position within the growing tissue
      as the best predictor of cell-fate acquisition. We propose a self-regulatory
      mechanism that guides the regenerative process to identical outcome with minimal
      extrinsic information. The integrated approach that we have developed is simple
      and broadly applicable, and should help define predictive signatures of cellular
      behavior during the construction of complex tissues.

PMID- 29595472
TI  - Mechanism and consequence of abnormal calcium homeostasis in Rett syndrome
      astrocytes.
AB  - Astrocytes play an important role in Rett syndrome (RTT) disease progression.
      Although the non-cell-autonomous effect of RTT astrocytes on neurons was
      documented, cell-autonomous phenotypes and mechanisms within RTT astrocytes are
      not well understood. We report that spontaneous calcium activity is abnormal in
      RTT astrocytes in vitro, in situ, and in vivo. Such abnormal calcium activity is
      mediated by calcium overload in the endoplasmic reticulum caused by abnormal
      store operated calcium entry, which is in part dependent on elevated expression
      of TRPC4. Furthermore, the abnormal calcium activity leads to excessive
      activation of extrasynaptic NMDA receptors (eNMDARs) on neighboring neurons and
      increased network excitability in Mecp2 knockout mice. Finally, both the abnormal
      astrocytic calcium activity and the excessive activation of eNMDARs are caused by
      Mecp2 deletion in astrocytes in vivo. Our findings provide evidence that abnormal
      calcium homeostasis is a key cell-autonomous phenotype in RTT astrocytes, and
      reveal its mechanism and consequence.

PMID- 29595473
TI  - Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate
      strand passage.
AB  - Type II topoisomerases manage DNA supercoiling and aid chromosome segregation
      using a complex, ATP-dependent duplex strand passage mechanism. Type IIB
      topoisomerases and their homologs support both archaeal/plant viability and
      meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises
      two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA
      segments and link ATP turnover to DNA transport is poorly understood. Using
      multiple biochemical approaches, we show that Top6B, which harbors the ATPase
      activity of topo VI, recognizes and exploits the DNA crossings present in
      supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association
      in turn induces extensive DNA bending, which is needed to support duplex cleavage
      by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover
      recognition and ATP binding with strand scission, providing useful insights into
      the operation of type IIB topoisomerases and related meiotic recombination and
      GHKL ATPase machineries.

PMID- 29595474
TI  - Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent
      regulation of G1-length.
AB  - Animal cells within a tissue typically display a striking regularity in their
      size. To date, the molecular mechanisms that control this uniformity are still
      unknown. We have previously shown that size uniformity in animal cells is
      promoted, in part, by size-dependent regulation of G1 length. To identify the
      molecular mechanisms underlying this process, we performed a large-scale small
      molecule screen and found that the p38 MAPK pathway is involved in coordinating
      cell size and cell cycle progression. Small cells display higher p38 activity and
      spend more time in G1 than larger cells. Inhibition of p38 MAPK leads to loss of
      the compensatory G1 length extension in small cells, resulting in faster
      proliferation, smaller cell size and increased size heterogeneity. We propose a
      model wherein the p38 pathway responds to changes in cell size and regulates G1
      exit accordingly, to increase cell size uniformity.

PMID- 29595476
TI  - [Treatment of a unilateral Brodie's syndrome by surgical contraction of the
      maxillae].
AB  - INTRODUCTION: Brodie's syndrome consists in a transverse occlusal discrepancy in
      relation with an excessive width of the maxilla, a narrow mandible or a
      combination of both, leading to lateral scissors bite. This kind of infrequent
      malocclusion is usually treated by orthodontics alone in children. In adults,
      additional orthognathic surgery id often required. We present a case of
      unilateral Brodie's syndrome treated by surgical contraction of the maxillae.
      OBSERVATION: A 22-year-old patient presented with a left scissors bite and severe
      unilateral molar overbite. After failure of an attempt to ingress the left molars
      by help of a sub-apical corticotomy and anchorage mini-screws, the patient was
      referred for surgery. The mandible being considered as normal, a segmented Le
      Fort I osteotomy was planned, combining a contraction (4mm) and an impaction
      (4mm) of the left maxilla. This allowed for an immediate correction of the
      skeletal discrepancy and for the achievement of orthodontics in less than 6
      months. DISCUSSION: Le Fort I osteotomy provides a good access to the sagittal
      suture. Maxillary contraction is an uncommon procedure that enables a quick
      management of scissors bite and doesn't need any patient cooperation. Treatment
      time is reduced and the need for intraoral devices is limited.

PMID- 29595477
TI  - Corrigendum to "Stationarity of health expenditures and GDP: Evidence from panel
      unit root tests with heterogeneous structural breaks" [J. Health Econ. 22 (2003)
      313-323].

PMID- 29595475
TI  - Multi-view light-sheet imaging and tracking with the MaMuT software reveals the
      cell lineage of a direct developing arthropod limb.
AB  - During development, coordinated cell behaviors orchestrate tissue and organ
      morphogenesis. Detailed descriptions of cell lineages and behaviors provide a
      powerful framework to elucidate the mechanisms of morphogenesis. To study the
      cellular basis of limb development, we imaged transgenic fluorescently-labeled
      embryos from the crustacean Parhyale hawaiensis with multi-view light-sheet
      microscopy at high spatiotemporal resolution over several days of embryogenesis.
      The cell lineage of outgrowing thoracic limbs was reconstructed at single-cell
      resolution with new software called Massive Multi-view Tracker (MaMuT). In silico
      clonal analyses suggested that the early limb primordium becomes subdivided into
      anterior-posterior and dorsal-ventral compartments whose boundaries intersect at
      the distal tip of the growing limb. Limb-bud formation is associated with spatial
      modulation of cell proliferation, while limb elongation is also driven by
      preferential orientation of cell divisions along the proximal-distal growth axis.
      Cellular reconstructions were predictive of the expression patterns of limb
      development genes including the BMP morphogen Decapentaplegic.

PMID- 29595478
TI  - Abortion: access and safety worldwide.

PMID- 29595479
TI  - Diagnosis of heavy menstrual bleeding: a change in direction.

PMID- 29595480
TI  - Brexit and the NHS.

PMID- 29595481
TI  - Addressing social determinants to end tuberculosis.

PMID- 29595482
TI  - The Lancet Commission on tuberculosis: building a tuberculosis-free world.

PMID- 29595483
TI  - Offline: Liberty vs equity in global health.

PMID- 29595484
TI  - Trump Administration's new direction for Medicaid.

PMID- 29595485
TI  - New York Challenge sets high bar for HPV vaccination.

PMID- 29595486
TI  - Commitments to an end to tuberculosis renewed in India.

PMID- 29595487
TI  - Action on minimum unit pricing of alcohol: a broader need.

PMID- 29595490
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET.

PMID- 29595497
TI  - Department of Error.

PMID- 29595493
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET.

PMID- 29595489
TI  - Planetary health: a new sociopolitical framework is urgently needed.

PMID- 29595488
TI  - Systems modelling tools to support policy and planning.

PMID- 29595496
TI  - Department of Error.

PMID- 29595491
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET.

PMID- 29595494
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET.

PMID- 29595500
TI  - B cells or T cells in TB: a continuing conundrum.

PMID- 29595492
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET.

PMID- 29595498
TI  - Time to blow away the cobwebs.

PMID- 29595499
TI  - Defining the best regimen to treat isoniazid-resistant tuberculosis.

PMID- 29595495
TI  - Graded exercise self-help for chronic fatigue syndrome in GETSET - Authors'
      reply.

PMID- 29595501
TI  - Pan-tuberculosis regimens: an argument for.

PMID- 29595502
TI  - Pan-tuberculosis regimens: an argument against.

PMID- 29595503
TI  - Tuberculosis research and development: seeding the future.

PMID- 29595507
TI  - Busy day at the clinic.

PMID- 29595504
TI  - Tuberculosis transmission during the subclinical period: could unrelated cough
      play a part?

PMID- 29595513
TI  - Corrections.

PMID- 29595506
TI  - The changing face of tuberculosis care in Russia.

PMID- 29595514
TI  - Corrections.

PMID- 29595505
TI  - Time to revise WHO-recommended definitions of MDR-TB treatment outcomes.

PMID- 29595518
TI  - Magnetic graphene enabled tunable microwave absorber via thermal control.
AB  - By synthesizing nitrogen-doped graphene (NG) via a facile thermal annealing
      method, a fine control of the amount and location of doped nitrogen as well as
      the oxygen-containing functional groups is achieved with varying annealing
      temperature. The favorable magnetic properties have been achieved for N-doped rGO
      samples obtained at two temperatures of all NG samples, i.e., 500  degrees C and
      900  degrees C with saturation magnetization of 0.63 emu g-1 and 0.67 emu g-1 at
      2 K, respectively. This is attributed to the optimized competition of the N
      doping and reduction process at 500  degrees C and the dominated reduction
      process at 900  degrees C. NG obtained at 300  degrees C affords the best overall
      absorbing performance: when the absorber thickness is 3.0 mm, the maximum
      absorption was -24.6 dB at 8.51 GHz, and the absorption bandwidth was 4.89 GHz
      (7.55-12.44 GHz) below -10 dB. It owes its large absorbing intensity to the good
      impedance match and significant dielectric loss. The broad absorption bandwidth
      benefits from local fluctuations of dielectric responses contributed by competing
      mechanisms. Despite the significant contribution from materials loss to the
      absorption, the one quarter-wavelength model is found to be responsible for the
      reflection loss peak positions. Of particular significance is that an appropriate
      set of electromagnetic parameters associated with reasonable reduction is readily
      accessible by convenient control of annealing temperature to modulate the
      microwave absorbing features of graphene. Thus, NG prepared by thermal annealing
      promises to be a highly efficient microwave absorbent.

PMID- 29595521
TI  - Can disorder act as a chemical pressure? An optical study of the Hubbard model.
AB  - The optical properties have been studied using the dynamical mean-field theory on
      a disordered Hubbard model. Despite the fact that disorder turns a metal to an
      insulator in high dimensional correlated materials, we notice that it can enhance
      certain metallic behavior as if a chemical pressure is applied to the system
      resulting in an increase of the effective lattice bandwidth (BW). We study
      optical properties in such a scenario and compare results with experiments where
      the BW is changed through isovalent chemical substitution (keeping electron
      filling unaltered) and obtain remarkable similarities vindicating our claim. We
      also make the point that these similarities differ from some other forms of BW
      tuned optical effects.

PMID- 29595511
TI  - The global tuberculosis epidemic and progress in care, prevention, and research:
      an overview in year 3 of the End TB era.
AB  - Tuberculosis is the number one cause of death from infectious disease globally
      and drug-resistant forms of the disease are a major risk to global health
      security. On the occasion of World Tuberculosis Day (March 24, 2018), we provide
      an up-to-date review of the status of the tuberculosis epidemic, recommended
      diagnostics, drug treatments and vaccines, progress in delivery of care and
      prevention, progress in research and development, and actions needed to
      accelerate progress. This Review is presented in the context of the UN
      Sustainable Development Goals and WHO's End TB Strategy, which share the aim of
      ending the global tuberculosis epidemic. In 2016, globally there were an
      estimated 10.4 million new cases of tuberculosis, and 600 000 new cases with
      resistance to rifampicin (the most powerful first-line drug). All countries and
      age groups are affected by tuberculosis, but most cases (90%) in 2016 were in
      adults, and almost two-thirds were accounted for by seven countries: India,
      Indonesia, China, Philippines, Pakistan, South Africa, and Nigeria. The sex ratio
      (male to female) was 1.9 and 10% of patients with newly diagnosed tuberculosis
      were also HIV-positive. There were 1.7 million deaths from tuberculosis in 2016,
      including 0.4 million deaths among people co-infected with HIV (officially
      classified as deaths caused by HIV/AIDS). Progress in care and prevention means
      that the global mortality rate (deaths per 100 000 people per year) is decreasing
      by 3.4% per year and incidence (new cases per 100 000 people per year) is
      decreasing by 1.9% per year. From 2000 to 2016, the annual global number of
      tuberculosis deaths decreased by 24% and the mortality rate declined by 37%.
      Worldwide, an estimated 53 million deaths were averted through successful
      treatment. Nonetheless, major gaps in care and prevention remain. For example,
      the 6.3 million new cases of tuberculosis reported globally in 2016 represented
      only 61% of the estimated incidence; only one in five of the estimated number of
      people with drug-resistant tuberculosis was enrolled in treatment. Pipelines for
      new diagnostics, drugs, and vaccines are progressing, but slowly. Actions needed
      to accelerate progress towards global milestones and targets for reductions in
      the burden of tuberculosis disease set for 2020, 2025, 2030, and 2035 include
      closing coverage gaps in testing, reporting of cases, and overall access to
      health care, especially in countries that account for the largest share of the
      global gap; multisectoral efforts to reduce prevalence of major risk factors for
      infection and disease; and increased investment in research and development.

PMID- 29595515
TI  - Hypocapnia correction as a working mechanism for breathing retraining in asthma -
      Authors' reply.

PMID- 29595512
TI  - Hypocapnia correction as a working mechanism for breathing retraining in asthma.

PMID- 29595508
TI  - Sustaining a national tuberculosis control programme during civil crisis: 6 years
      of experience in Syria.

PMID- 29595520
TI  - Nickel nanoparticle-stabilized room-temperature blue-phase liquid crystals.
AB  - Blue-phase liquid crystals (BPLCs) are regarded as a potential candidate for the
      next generation of optical devices, but they appear in a narrow temperature
      range, which restricts their applicability. The nanoparticle (NP) stabilization
      of BPLCs, is usually about either simple-cubic BP (BPII) or body-centered-cubic
      BP (BPI). Hence, NP-stabilized BPIIs and BPIs possessing wide temperature ranges
      have been scarcely reported. Here, nickel nanoparticles (Ni NPs) were synthesized
      and introduced into a BPLC. The concentration-dependent temperature range effects
      of Ni NPs on the BPLC were investigated. A trace amount of Ni NPs could stabilize
      the BPLC and increase the temperature ranges of BPII and BPI; this is
      attributable to the Ni NPs tending to be trapped at the joints of the
      disclination lines, as a result of the elastic interaction, stabilizing the
      overall lattice structure of the BPLC. When doped with 0.05 wt% Ni NPs, the
      mixture shows a wider range with 7.7  degrees C than the range with 5.9  degrees
      C of the BPLC without Ni NPs. Meanwhile, the phase sequence and range of the
      aforementioned phases are reproducible upon heating and cooling, which shows that
      the BPLCs doped with Ni NPs are thermodynamically stable.

PMID- 29595522
TI  - Armours for soft bodies: how far can bioinspiration take us?
AB  - The development of armour is as old as the dawn of civilization. Early man looked
      to natural structures to harvest or replicate for protection, leaning on
      millennia of evolutionary developments in natural protection. Since the advent of
      more modern weaponry, Armor development has seemingly been driven more by
      materials research than bio-inspiration. However, parallels can still be drawn
      between modern bullet-protective armours and natural defensive structures. Soft
      armour for handgun and fragmentation threats can be likened to mammalian skin,
      and similarly, hard armour can be compared with exoskeletons and turtle shells.
      Via bio-inspiration, it may be possible to develop structures previously un
      researched for ballistic protection. This review will cover current modern
      ballistic protective structures focusing on energy dissipation and absorption
      methods, and their natural analogues. As all armour is a compromise between
      weight, flexibility and protection, the imbricated structure of scaled skin will
      be presented as a better balance between these factors.

PMID- 29595519
TI  - Ultrafast carrier dynamics and third-order nonlinear optical properties of
      AgInS2/ZnS nanocrystals.
AB  - Broad photoluminescence (PL) emission, a large Stokes shift and extremely long
      lived radiative lifetimes are the characteristics of ternary I-III-VI
      semiconductor nanocrystals (NCs), such as CuInS2 and AgInS2. However, the lack of
      understanding regarding the intriguing PL mechanisms and photo-carrier dynamics
      limits their further applications. Here, AgInS2 and AgInS2/ZnS NCs were
      chemically synthesized and their carrier dynamics were studied by time-resolved
      PL spectroscopy. The results demonstrated that the surface defect state, which
      contributed dominantly to the non-radiative decay processes, was effectively
      passivated through ZnS alloying. Femtosecond transient absorption spectroscopy
      was also used to investigate the carrier dynamics, revealing the electron storage
      at the surface state and donor state. Furthermore, the two photon absorption
      properties of AgInS2 and AgInS2/ZnS NCs were measured using an open-aperture Z
      scan technique. The improved third-order nonlinear susceptibility [Formula: see
      text] of AgInS2 through ZnS alloying demonstrates potential application in two
      photon PL biological imaging.

PMID- 29595523
TI  - Preparation and characterization of WSe2 nano-films by magnetron sputtering and
      vacuum selenization.
AB  - Graphene-structure WSe2 nano-films (NFMs) were prepared by magnetron sputtering
      and vacuum selenization. The as synthesized WSe2 NFMs were characterized using
      various techniques such as SEM, XRD and EDS. Our work provides a simple and
      effective method to prepare WSe2 NFMs. We have observed the high photo
      responsivity of WSe2 NFMs up to 10 A W-1, which is 40% higher than the previously
      reported data. Our photoelectrochemical tests demonstrate that WSe2 NFMs have
      excellent photoelectric properties, indicating that NFMs have a wide application
      potentialsin solar cells and optoelectronic devices.

PMID- 29595510
TI  - Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG
      vaccinated healthy adults in South Africa: a randomised, double-blind, placebo
      controlled phase 1 trial.
AB  - BACKGROUND: A vaccine that prevents pulmonary tuberculosis in adults is needed to
      halt transmission in endemic regions. This trial aimed to assess the safety and
      immunogenicity of three administrations at varying doses of antigen and adjuvant
      of an investigational vaccine (ID93 + GLA-SE) compared with placebo in previously
      BCG-vaccinated healthy adults in a tuberculosis endemic country. METHODS: In this
      randomised, double-blind, placebo-controlled phase 1 trial, we enrolled HIV
      negative, previously BCG-vaccinated adults (aged 18-50 years), with no evidence
      of previous or current tuberculosis disease, from among community volunteers in
      the Worcester region of Western Cape, South Africa. Participants were randomly
      assigned to receive varying doses of ID93 + GLA-SE or saline placebo at day 0,
      day 28, and day 112. Enrolment into each cohort was sequential. Cohort 1
      participants were Mycobacterium tuberculosis uninfected (as defined by negative
      QuantiFERON [QFT] status), and received 10 MUg ID93 plus 2 MUg GLA-SE, or
      placebo; in cohorts 2-4, QFT-negative or positive participants received
      escalating doses of vaccine or placebo. Cohort 2 received 2 MUg ID93 plus 2 MUg
      GLA-SE; cohort 3 received 10 MUg ID93 plus 2 MUg GLA-SE; and cohort 4 received 10
      MUg ID93 plus 5 MUg GLA-SE. Dose cohort allocation was sequential; randomisation
      within a cohort was according to a randomly-generated sequence (3 to 1 in cohort
      1, 5 to 1 in cohorts 2-4). The primary endpoint was safety of ID93 + GLA-SE as
      defined by solicited and unsolicited adverse events up to 28 days after each
      study injection and serious adverse events for the duration of the study.
      Specific immune responses were measured by intracellular cytokine staining, flow
      cytometry, and ELISA. All analyses were done according to intention to treat,
      with additional per-protocol analyses for immunogenicity outcomes. This trial is
      registered with ClinicalTrials.gov, number NCT01927159. FINDINGS: Between Aug 30,
      2013, and Sept 4, 2014, 227 individuals consented to participate; 213 were
      screened (three participants were not included as study number was already met
      and 11 withdrew consent before screening occurred, mostly due to relocation or
      demands of employment). 66 healthy, HIV-negative adults were randomly allocated
      to receive the vaccine (n=54) or placebo (n=12). All study participants received
      day 0 and day 28 study injections; five participants did not receive an injection
      on day 112. ID93 + GLA-SE was well tolerated; no severe or serious vaccine
      related adverse events were recorded. Vaccine dose did not affect frequency or
      severity of adverse events, but mild injection site adverse events and flu-like
      symptoms were common in M tuberculosis-infected participants compared with
      uninfected participants. Vaccination induced durable antigen-specific IgG and Th1
      cellular responses, which peaked after two administrations. Vaccine dose did not
      affect magnitude, kinetics, or profile of antibody and cellular responses.
      Earlier boosting and greater T-cell differentiation and effector-like profiles
      were seen in M tuberculosis-infected than in uninfected vaccinees.
      INTERPRETATION: Escalating doses of ID93 + GLA-SE induced similar antigen
      specific CD4-positive T cell and humoral responses, with an acceptable safety
      profile in BCG-immunised, M tuberculosis-infected individuals. The T-cell
      differentiation profiles in M tuberculosis-infected vaccinees suggest priming
      through natural infection. While cohort sample sizes in this phase 1 trial were
      small and results should be interpreted in context, these data support efficacy
      testing of two administrations of the lowest (2 MUg) ID93 vaccine dose in
      tuberculosis endemic populations. FUNDING: Aeras and the Paul G Allen Family
      Foundation.

PMID- 29595524
TI  - Protein sequencing via nanopore based devices: a nanofluidics perspective.
AB  - Proteins perform a huge number of central functions in living organisms, thus all
      the new techniques allowing their precise, fast and accurate characterization at
      single-molecule level certainly represent a burst in proteomics with important
      biomedical impact. In this review, we describe the recent progresses in the
      developing of nanopore based devices for protein sequencing. We start with a
      critical analysis of the main technical requirements for nanopore protein
      sequencing, summarizing some ideas and methodologies that have recently appeared
      in the literature. In the last sections, we focus on the physical modelling of
      the transport phenomena occurring in nanopore based devices. The multiscale
      nature of the problem is discussed and, in this respect, some of the main
      possible computational approaches are illustrated.

PMID- 29595516
TI  - A Rare Cause of Congenital Adrenal Hyperplasia: Clinical and Genetic Findings and
      Follow-up Characteristics of Six Patients with 17-Hydroxylase Deficiency
      Including Two Novel Mutations
AB  - Objective: 17alpha-hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of
      congenital adrenal hyperplasia (CAH), characterized by hypertension and varying
      degrees of ambiguous genitalia and delayed puberty. The disease is associated
      with bi-allelic mutations in the CYP17A1 gene located on chromosome 10q24.3. We
      aimed to present clinical and genetic findings and follow-up and treatment
      outcomes of 17OHD patients. Methods: We evaluated six patients with 17OHD from
      five families at presentation and at follow up. Standard deviation score of all
      auxological measurements was calculated according to national data and karyotype
      status. CYP17A1 gene sequence alterations were investigated in all patients.
      Results: The mean (+/-standard deviation) age of patients at presentation and
      follow-up time was 14.6+/-4.2 and 5.0+/-2.7 years respectively. Five patients
      were referred to us because of delayed puberty and primary amenorrhea and four
      for hypertension. One novel single nucleotide insertion leading to frame shift
      and another novel variant occurring at an ultra rare position, leading to a
      missense change, are reported, both of which caused 17OHD deficiency. Steroid
      replacement was started. The three patients with 46,XY karyotype who were raised
      as females underwent gonadectomy. Osteoporosis was detected in five patients.
      Four patients needed antihypertensive treatment. Improvement in osteoporosis was
      noted with gonadal steroid replacement and supportive therapy. Conclusion: 17OHD,
      a rare cause of CAH, should be kept in mind in patients with pubertal delay
      and/or hypertension. Patients with 46,XY who are raised as females require
      gonadectomy. Due to late diagnosis, psychological problems, gender selection,
      hypertension and osteoporosis are important health problems affecting a high
      proportion of these patients.

PMID- 29595517
TI  - Parental Perception of Terminology of Disorders of Sex Development in Western
      Turkey
AB  - Objective: Disorders of sex development (DSD) is a nomenclature intended to
      defeat the discomfort of families and patients and has found worldwide usage. The
      aim of this study was to address the perception and usage of terminology among
      the parents of DSD patients in a tertiary center in western Turkey. Methods: The
      records of the DSD council (multidisciplinary team where each patient with DSD is
      discussed) between years 2008-2015 were reviewed retrospectively. Data including
      details of the management process, patient characteristics and follow-up details
      were noted. Then inquiries reflecting parental perception about terminology were
      implemented during clinical visits. Results: In total, 121 patients were
      evaluated in monthly meetings of the DSD council and 79 inquiries were completed.
      Fifty-one percent of the families admitted knowing the terms DSD, ambiguous
      genitalia, "dubious genitals" and intersex. However, only 2% preferred using DSD,
      6% intersex and 14% ambiguous genitalia. Fifty-two percent of the parents used a
      disease name in Latin (mostly hypospadias) addressing the disorder. The offspring
      of 69% of the parents who were familiar with the name "dubious genitals" were
      diagnosed in the neonatal period. The preferred terminology used by parents was
      strongly associated with the terminology used most commonly in the medical
      speciality their child most often attended. Conclusion: Each country has its own
      social norms. We suggest therefore that local committees including medical
      professionals, patients and families should be employed to develop proper
      terminology.

PMID- 29595525
TI  - Electrical and optical evaluation of n-type doping in In x Ga(1-x)P nanowires.
AB  - To harvest the benefits of III-V nanowires in optoelectronic devices, the
      development of ternary materials with controlled doping is needed. In this work,
      we performed a systematic study of n-type dopant incorporation in dense In x Ga(1
      x)P nanowire arrays using tetraethyl tin (TESn) and hydrogen sulfide (H2S) as
      dopant precursors. The morphology, crystal structure and material composition of
      the nanowires were characterized by use of scanning electron microscopy,
      transmission electron microscopy and energy dispersive x-ray analysis. To
      investigate the electrical properties, the nanowires were broken off from the
      substrate and mechanically transferred to thermally oxidized silicon substrates,
      after which electron beam lithography and metal evaporation were used to define
      electrical contacts to selected nanowires. Electrical characterization, including
      four-probe resistivity and Hall effect, as well as back-gated field effect
      measurements, is combined with photoluminescence spectroscopy to achieve a
      comprehensive evaluation of the carrier concentration in the doped nanowires. We
      measure a carrier concentration of ~1 * 1016 cm-3 in nominally intrinsic
      nanowires, and the maximum doping level achieved by use of TESn and H2S as dopant
      precursors using our parameters is measured to be ~2 * 1018 cm-3, and ~1 * 1019
      cm-3, respectively (by Hall effect measurements). Hence, both TESn and H2S are
      suitable precursors for a wide range of n-doping levels in In x Ga(1-x)P
      nanowires needed for optoelectronic devices, grown via the vapor-liquid-solid
      mode.

PMID- 29595526
TI  - Theory of in-plane current induced spin torque in metal/ferromagnet bilayers.
AB  - Using a semiclassical approach that simultaneously incorporates the spin Hall
      effect (SHE), spin diffusion, quantum well states, and interface spin-orbit
      coupling (SOC), we address the interplay of these mechanisms as the origin of the
      spin-orbit torque (SOT) induced by in-plane currents, as observed in the normal
      metal/ferromagnetic metal bilayer thin films. Focusing on the bilayers with a
      ferromagnet much thinner than its spin diffusion length, such as Pt/Co with  ~10
      nm thickness, our approach addresses simultaneously the two contributions to the
      SOT, namely the spin-transfer torque (SHE-STT) due to SHE-induced spin injection,
      and the inverse spin Galvanic effect spin-orbit torque (ISGE-SOT) due to SOC
      induced spin accumulation. The SOC produces an effective magnetic field at the
      interface, hence it modifies the angular momentum conservation expected for the
      SHE-STT. The SHE-induced spin voltage and the interface spin current are mutually
      dependent and, hence, are solved in a self-consistent manner. The result suggests
      that the SHE-STT and ISGE-SOT are of the same order of magnitude, and the spin
      transport mediated by the quantum well states may be an important mechanism for
      the experimentally observed rapid variation of the SOT with respect to the
      thickness of the ferromagnet.

PMID- 29595509
TI  - Comparison of different treatments for isoniazid-resistant tuberculosis: an
      individual patient data meta-analysis.
AB  - BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is
      the most common form of drug resistance, and is associated with failure, relapse,
      and acquired rifampicin resistance if treated with first-line anti-tuberculosis
      drugs. The aim of the study was to compare success, mortality, and acquired
      rifampicin resistance in patients with INH-R pulmonary tuberculosis given
      different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a
      fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core
      regimen of REZ. METHODS: Studies with regimens and outcomes known for individual
      patients with INH-R tuberculosis were eligible, irrespective of the number of
      patients if randomised trials, or with at least 20 participants if a cohort
      study. Studies were identified from two relevant systematic reviews, an updated
      search of one of the systematic reviews (for papers published between April 1,
      2015, and Feb 10, 2016), and personal communications. Individual patient data
      were obtained from authors of eligible studies. The individual patient data meta
      analysis was performed with propensity score matched logistic regression to
      estimate adjusted odds ratios (aOR) and risk differences of treatment success
      (cure or treatment completion), death during treatment, and acquired rifampicin
      resistance. Outcomes were measured across different treatment regimens to assess
      the effects of: different durations of REZ (<=6 months vs >6 months); addition of
      a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6
      months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6
      months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or
      more of REZ). The overall quality of the evidence was assessed using GRADE
      methodology. FINDINGS: Individual patient data were requested for 57 cohort
      studies and 17 randomised trials including 8089 patients with INH-R tuberculosis.
      We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies
      received regimens related to the study objectives. Compared with a daily regimen
      of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to
      8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for
      subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of
      (H)REZ was associated with significantly greater treatment success (aOR 2.8, 95%
      CI 1.1-7.3), but no significant effect on mortality (aOR 0.7, 0.4-1.1) or
      acquired rifampicin resistance (aOR 0.1, 0.0-1.2). Compared with 6 months or more
      of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3
      months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol)
      was associated with significantly worse treatment success (aOR 0.4, 0.2-0.7). The
      quality of the evidence was very low for all outcomes and treatment regimens
      assessed, owing to the observational nature of most of the data, the diverse
      settings, and the imprecision of estimates. INTERPRETATION: In patients with INH
      R tuberculosis, compared with treatment with at least 6 months of daily REZ,
      addition of a fluoroquinolone was associated with better treatment success,
      whereas addition of streptomycin was associated with less treatment success;
      however, the quality of the evidence was very low. These results support the
      conduct of randomised trials to identify the optimum regimen for this important
      and common form of drug-resistant tuberculosis. FUNDING: World Health
      Organization and Canadian Institutes of Health Research.

PMID- 29595527
TI  - Realism and Relativism in the Development of Nursing as a Discipline.
AB  - In today's era of nursing, the role of a unique disciplinary knowledge that is
      grounded in philosophy is essential to inform nursing practice, fill knowledge
      gaps, improve the quality of nursing education, and guide the theoretical
      development of nursing. Realism and relativism have contributed to the
      development of the nursing discipline by providing the basis of evidence-based
      nursing practice, nursing research, nursing education, and theoretical
      construction. This article explores the role of realism and relativism in the
      development of the discipline of nursing and presents their contributions to the
      work of nurse clinicians, nurse researchers, nurse educators, and nurse
      theorists.

PMID- 29595528
TI  - Effect of Methylprednisolone on Pain Management in Total Knee or Hip
      Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled
      Trials.
AB  - BACKGROUND: Total joint arthroplasty (TJA) has been reported to be a successful
      strategy for patients with advanced osteoarthritis; however, early postoperative
      pain has become an unresolved issue. Perioperative methylprednisolone (MP)
      administration in TJA is an important and controversial topic. This study was
      conducted to assess the efficacy and safety of MP for pain management after total
      knee or hip arthroplasty (TKA/THA). MATERIALS AND METHODS: PubMed, Embase, and
      the Cochrane Library were searched for randomized controlled trials comparing MP
      versus placebo for patients undergoing TKA/THA. Related indicators that reflected
      the efficacy and safety for pain management were evaluated by meta-analysis.
      RESULTS: Six randomized controlled trials involving a total of 350 patients met
      the inclusion criteria. The outcomes showed that intravenous MP significantly
      reduced pain scores at 6 and 24 hours during activity after TKA and THA but local
      use of MP had no clear benefit in reducing pain scores compared with the control
      group. There was no significant difference in VAS at 24 hours at rest and 48
      hours during activity after TKA and THA. In addition, MP was associated with a
      reduction of morphine consumption at 24 hours after TKA. Furthermore, patients
      receiving MP had an obvious inflammatory control and improving postoperative
      nausea and vomiting and the use of MP was not associated with a significant
      increase in the risk of complications. There was no significant difference in the
      range of knee motion and length of hospital stay in both groups. CONCLUSIONS:
      This study showed that intravenous MP significantly alleviated early
      postoperative pain and the incidence of postoperative nausea and vomiting after
      TKA and THA. For safety, intravenous MP as a promising strategy in rapid recovery
      to TJA.

PMID- 29595529
TI  - EC50 of Epidural Ropivacaine Combined With Dexmedetomidine for Labor Analgesia.
AB  - BACKGROUND: It has been reported that the optimal concentration of epidural
      dexmedetomidine for labor analgesia is 0.5 MUg/mL when combined with 0.1%
      ropivacaine. This study investigated the median effective concentration (EC50) of
      epidural ropivacaine for labor analgesia when combined with 0.5 MUg/mL
      dexmedetomidine. MATERIALS AND METHODS: Sixty full-term primiparas were enrolled
      and divided into 2 groups in this prospective study. Group D received 10 mL
      solution (ropivacaine+0.5 MUg/mL dexmedetomidine) in the induction of epidural
      anesthesia, and group C (control group) received 10 mL of ropivacaine alone. The
      dose of epidural ropivacaine was decided by using the up-and-down sequential
      allocation method with an initial concentration of 0.1%*0.01% gradient. Effective
      analgesia was defined as the visual analogue scale for pain as <=3 within 30
      minutes after epidural injection when cervical dilation is about 2 cm. The EC50
      of ropivacaine was calculated by the Massey formula. Hemodynamic parameters, the
      stages of labor, and fetal heart rate were recorded. Neonatal Apgar scores and
      umbilical artery pH were also recorded. The side effects, if any, were noted.
      RESULTS: The EC50 of ropivacaine was 0.062% (95% confidence interval [CI], 0.058%
      0.066%) in the group D, and 0.083% (95% CI, 0.077%-0.089%) in the group C, there
      was a significant difference between the groups (P<0.05). CONCLUSIONS: The EC50
      of epidural ropivacaine for labor analgesia was 0.083% (95% CI, 0.077%-0.089%)
      and decreased to 0.062% (95% CI, 0.058%-0.066%) when combined with 0.5 MUg/mL
      dexmedetomidine (http://www.chictr.org.cn, registration number: ChiCTR-OPC
      16008548).

PMID- 29595530
TI  - Cor Pulmonale in Children With Acute Respiratory Failure on Venovenous
      Extracorporeal Membrane Oxygenation.

PMID- 29595531
TI  - Sedative and Analgesic Drug Sequestration After a Single Bolus Injection in an Ex
      Vivo Extracorporeal Membrane Oxygenation Infant Circuit.
AB  - Patient sedation and analgesia on extracorporeal membrane oxygenation (ECMO) is
      vital for safety and comfort. However, adsorption to the circuit may alter drug
      pharmacokinetics and remains poorly characterized. This study characterizes drug
      adsorption of morphine, fentanyl, midazolam, and dexmedetomidine in an ex vivo
      infant ECMO circuit utilizing polymethylpentene (PMP) membrane oxygenator (MO)
      with protein-bounded polyvinylchloride (PVC) tubing. Twelve closed-loop ex vivo
      ECMO circuits were prepared using P.h.i.s.i.o (phosphorylcholine)-coated PVC
      tubing (Sorin Group USA, Inc.) and a Quadrox-iD pediatric polymethylpentene MO
      (Maquet Cardiopulmonary AG). Once the circuits were primed and running, a single
      medication was injected as a bolus into the circuit with three circuits per drug.
      Drug samples were drawn following injection, at 2, 5, 15, 30, 60, 120 minutes and
      at 4, 12, 24, 36, and 48 hours and analyzed using ultra high-performance liquid
      chromatography with mass spectrometry. Compared with morphine, the other drugs
      are highly sequestered with fentanyl 68.5%, dexmedetomidine 50.8%, and midazolam
      26.2% affecting the availability of free drug in the circuit. Sequestration of
      fentanyl, midazolam, and dexmedetomidine in an ECMO circuit with Phisio-coated
      PVC tubing and PMP MO may limit drug delivery to infants. Future in vivo studies
      are needed to determine the clinical impact of sequestration.

PMID- 29595532
TI  - Development of an Ex-Situ Limb Perfusion System for a Rodent Model.
AB  - Ex-situ perfusion (ESP) is a promising method in preserving vascularized
      composite tissue allografts (VCAs) with potential to widen donor procurement to
      larger geographic areas. To optimize the method of preservation, we developed a
      small animal model to conduct biomolecular investigations. Twenty rat hind limbs
      (18.2 +/- 1.3 g) were procured and connected to our custom-made ESP system.
      Perfusion pressure and flow parameters were measured with hourly blood gas
      analysis under near-normothermic (30-35C) conditions. Perfusate was prepared with
      swine hemoglobin (6-9 g/dL) and STEEN Solution. After 6 hours of perfusion,
      gastrocnemius muscles were evaluated for their histology and metabolomic
      profiling. Following 3 sets of experiments, perfusion was maintained at an
      average flow of 0.9 +/- 0.24 mL/min and resulted in lactate levels of 3.78 +/-
      1.02 mmol/L. Metabolomic analysis revealed maintained cellular energy stores
      (total adenylates perfusion 0.698 +/- 0.052 versus baseline 0.685 +/- 0.091
      umols/ug, p = 0.831), and histologic analysis revealed no evidence of barotrauma
      or myodegeneration. Rat hind limbs were viable after 6 hours of ESP on our
      miniaturized ESP system. This study is the first to document the ex-situ hind
      limb perfusion platform on a rodent model. These experimental findings have
      potential to guide future research to extend the viable duration of VCA
      preservation.

PMID- 29595533
TI  - IDO1 Expression Is Associated With Immune Tolerance and Poor Prognosis in
      Patients With Surgically Resected Esophageal Cancer.
AB  - OBJECTIVES: To evaluate the relationship between indoleamine 2, 3-dioxygenase
      (IDO1) expression and tumoral immune status and clinical outcome in esophageal
      cancer. SUMMARY BACKGROUND DATA: IDO1 is a primary enzyme that generates
      immunosuppressive metabolites such as tryptophan and kynurenine. Like the PD-1/PD
      L1 pathway, IDO1 plays a major role in tumor immunology and is a potential immune
      based therapeutic target. METHODS: The expressions of IDO1, CD8 (a marker of
      cytotoxic T cells), FOXP3 [a marker of regulatory T cells (Treg)], and PD-L1 in
      305 curatively resected esophageal cancers were evaluated by immunostaining.
      RESULTS: Overall survival was significantly better in the IDO1 negative cases (n
      = 234) than in the IDO1 positive cases (n = 71) [log-rank P = 0.0041; hazard
      ratio (HR): 1.75; 95% confidence interval (CI): 1.12-2.67; P = 0.015]. CD8 high
      expression was significantly positively correlated with overall survival (log
      rank P = 0.025) and low IDO1 expression (P = 0.044). The inverse correlation
      between CD8 and IDO1 expressions was confirmed by double immunostaining for IDO1
      and CD8. Stratification based on IDO1 and CD8 expressions was also significantly
      associated with overall survival (log-rank P = 0.0024). In addition, the IDO1
      positive group was correlated with high counts of FOXP3-positive cells (P =
      0.020), but not with PD-L1 expression status (P = 0.19). CONCLUSIONS: IDO1
      expression was associated with an unfavorable clinical outcome in esophageal
      cancer, supporting its role as a prognostic biomarker. Combining the IDO1 and CD8
      statuses enabled further classification of the clinical outcomes of patients.

PMID- 29595534
TI  - Challenges in Complex Wound Management.

PMID- 29595535
TI  - "Jelly VAC" for Negative-Pressure Therapy for Complex Wound Closure: A Report of
      Two Cases.
AB  - CASE: A 35-year-old man sustained an open calcaneal fracture with bone loss, and
      a 57-year-old woman sustained an avulsion of the entirety of the plantar skin.
      Both patients were treated with multiple debridements and soft-tissue coverage.
      "Jelly-VAC" (vacuum-assisted closure) therapy was used after each debridement and
      during the soft-tissue coverage. CONCLUSION: Jelly-VAC therapy is a promising
      alternative that allows negative-pressure therapy with the use of ultrasound
      jelly to prevent air leakage into the wound. We propose using this technique in
      areas where obtaining a seal is difficult, where VAC therapy is contraindicated
      because of adhesive dressings (i.e., with damaged or poor-quality skin), or when
      long-term VAC therapy is needed to prevent wound maceration or there is a need
      for "VAC holidays."

PMID- 29595536
TI  - The Masquelet Technique for Thumb Metacarpal Reconstruction Following Trauma: A
      Case Report.
AB  - CASE: We describe an unusual case of an isolated close-range shotgun injury to
      the thumb with substantial osseous loss and intact vascularity, followed by
      treatment with the Masquelet technique and iliac crest tricortical bone autograft
      reconstruction. CONCLUSION: Gunshot injuries to the thumb with concomitant soft
      tissue and osseous loss are devastating. Reconstruction depends on the level of
      the injury, the severity of the soft-tissue and osseous damage, and the viability
      of the digit, as well as patient factors, including occupation, physical demands,
      and expectations.

PMID- 29595538
TI  - Labral Augmentation with Native Tissue Preservation with a 7.5-Year Follow-up: A
      Case Report.
AB  - CASE: Arthroscopic labral repair has resulted in excellent functional outcomes.
      However, extensive labral damage or diminutive size of the labrum may preclude a
      repair. In these cases, labral augmentation serves as an operative treatment
      option. We report the case of a labral augmentation with 7.5 years of follow-up,
      including intraoperative reexamination, which highlights the ability of an
      iliotibial band autograft to incorporate with the native labrum. CONCLUSION: When
      indicated in an appropriate patient, labral augmentation with an iliotibial band
      autograft is an established technique that can result in an excellent outcome.

PMID- 29595537
TI  - Chronic Osteomyelitis Caused by Haemophilus parainfluenzae: A Case Report.
AB  - CASE: A 14-year-old boy presented with a pathologic fracture of the distal aspect
      of the tibia and a remote history of a dog bite near the injury site. Imaging
      studies, biopsy, and presentation corroborated the diagnosis of chronic
      osteomyelitis. Multiple diagnostic methods were negative until an open biopsy
      identified Haemophilus parainfluenzae, a fastidious oropharyngeal bacterium, with
      polymerase chain reaction analysis. The patient underwent extensive debridement,
      placement of external fixation, and a year-long antibiotic therapy regimen. He
      subsequently required a tibial-fibular osteotomy at a second site with placement
      of an intramedullary nail for correction of a leg-length discrepancy. CONCLUSION:
      This case report illustrates the complex management of chronic osteomyelitis in
      pediatric patients, its sequelae, and the importance of considering treatment of
      atypical pathogens.

PMID- 29595539
TI  - Repeated forced-swimming test in intact female rats: behaviour, oestrous cycle
      and enriched environment.
AB  - Psychopharmacology used animal models to study the effects of drugs on brain and
      behaviour. The repeated forced-swimming test (rFST), which is used to assess the
      gradual effects of antidepressants on rat behaviour, was standardized only in
      males. Because of the known sex differences in rats, experimental conditions
      standardized for males may not apply to female rats. Therefore, the present work
      aimed to standardize experimental and housing conditions for the rFST in female
      rats. Young or adult Wistar female rats were housed in standard or enriched
      environments for different experimental periods. As assessed in tested and
      nontested females, all rats had reached sexual maturity by the time behavioural
      testing occurred. The rFST consisted of a 15-min session of forced swimming
      (pretest), followed by 5-min sessions at 1 (test), 7 (retest 1) and 14 days
      (retest 2) later. The oestrous cycle was registered immediately before every
      behavioural session. All sessions were videotaped for further analysis. The
      immobility time of female rats remained similar over the different sessions of
      rFST independent of the age, the phase of the oestrous cycle or the housing
      conditions. These data indicate that rFST in female Wistar rats may be
      reproducible in different experimental conditions.

PMID- 29595540
TI  - Sex-specific differences in cannabinoid-induced extracellular-signal-regulated
      kinase phosphorylation in the cingulate cortex, prefrontal cortex, and nucleus
      accumbens of Lister Hooded rats.
AB  - Sex-dependent differences have been consistently described in cannabinoid
      addiction research. In particular, we recently reported that female Lister Hooded
      rats display greater self-administration of the cannabinoid CB1 receptor agonist
      WIN55,212-2 (WIN) and stronger reinstatement of cannabinoid-seeking behavior than
      males. Cannabinoids modulate the phosphorylation of the extracellular-signal
      regulated kinase (ERK) pathway, leading to various forms of plasticity-related
      learning that likely affect operant behavior. However, whether or not the
      reported sex-dependent differences in cannabinoid-taking and cannabinoid-seeking
      behaviors may be related to a sexual dimorphic activation of the ERK pathway
      remains still to be determined. In the present study, we measured the level of
      phosphoERK-positive cells in the cingulate cortex (CG1), prefrontal cortex
      (PFCx), and nucleus accumbens of male and of intact (i.e. sham-operated) and
      ovariectomized female Lister Hooded rats 30 and 60 min after an acute,
      intravenous, injection of a dose of WIN (0.3 mg/kg) resembling the mean amount of
      drug daily self-administered by trained rats. We found that WIN significantly
      increased ERK activation in the CG1, PFCx, and nucleus accumbens in a sex time
      and, restricted to the cortical areas, layer-specific manner. Moreover, the
      comparison between intact and ovariectomized female rats revealed a significant
      role played by estrogens in WIN-elicited ERK activation. These results indicate,
      for the first time, the existence of a sexually dimorphic cannabinoid receptor
      dependent ERK activation that, restricted to the CG1 and PFCx, is ovarian hormone
      dependent.

PMID- 29595541
TI  - Co-administration of amphetamine with alcohol results in decreased alcohol
      withdrawal severity in adolescent rats.
AB  - Simultaneous use of stimulants and alcohol is a growing problem, particularly
      among older adolescents already prone to binge alcohol consumption. Adolescent
      rats consume high levels of alcohol when administered in a liquid diet and
      develop a strong alcohol withdrawal syndrome. We exploited this system to
      administer amphetamine in combination with alcohol and to test the effect of co
      administration of amphetamine on alcohol withdrawal-induced hypoactivity and
      overall withdrawal severity. The presence of dietary amphetamine (<=40 mg/l) had
      no effect on consumption of control or alcohol-containing diets. Measured in an
      activity chamber, alcohol withdrawal hypoactivity was reduced significantly by co
      administration of amphetamine with alcohol. Overall withdrawal severity was also
      reduced significantly when rats consumed amphetamine with alcohol. The results
      suggest that amphetamine co-use may mask physical signs of alcohol dependency and
      add to the importance of educational strategies pointing out the potential
      problems associated with co-use of stimulants and alcohol.

PMID- 29595542
TI  - Effects of daily morphine treatment on impulsivity in rats responding under an
      adjusting stop-signal reaction time task.
AB  - Opioids can enhance delay discounting and premature responding under attentional
      tasks that might reflect increased impulsivity; although it is not clear whether
      repeated opioid administration alters behavioral inhibition. Effects of morphine
      and amphetamine were determined before, during, and after daily morphine
      administration in rats responding under a stop-signal reaction time task,
      measuring behavioral inhibition and motor impulsivity. Rats (n=5) completed a two
      response sequence to earn food. Occasionally, a tone (stop signal) was presented
      signifying that food would only be presented if the second response was withheld.
      Responding after the stop signal measured inhibition, and responding before the
      start of the trial (premature) measured motor impulsivity. Before daily
      treatment, morphine (0.32-17.8 mg/kg, intraperitoneally) decreased premature
      responding but did not increase responding on stop trials, whereas amphetamine
      (0.1-3.2 mg/kg, intraperitoneally) increased premature responding. Daily morphine
      administration (3.2 mg/kg/day) enhanced its effects on premature responding but
      did not impact other effects. Daily morphine treatment diminished the effects of
      amphetamine on premature and timeout responding. Repeated morphine treatment
      increased motor impulsivity but did not enhance behavioral inhibition. These data
      add to studies elucidating the relationship between impulsivity and opioid
      treatment and suggest that opioids differentially impact impulsive behaviors.

PMID- 29595543
TI  - Protective Effect of Scopoletin Against Cerulein-Induced Acute Pancreatitis and
      Associated Lung Injury in Mice.
AB  - OBJECTIVE: The present study aimed to evaluate the protective effects of
      scopoletin (SC) on cerulein-induced acute pancreatitis (AP) and associated lung
      injury in mice. METHODS: Acute pancreatitis was induced in male Swiss mice by 6
      consecutive hourly intraperitoneal injections of cerulein (50 MUg/kg). Scopoletin
      was administered 1 hour (intraperitoneal, 10 mg/kg) after the first cerulein
      injection. RESULTS: Administration of SC attenuated the severity of AP and
      associated lung injury as shown by histology, reduced myeloperoxidase, and serum
      amylase activity. Further, the anti-inflammatory effect of SC was associated with
      a reduction of pancreatic and pulmonary proinflammatory cytokines (interleukin
      1beta and tumor necrosis factor alpha) and hydrogen sulfide. Moreover, SC
      inhibited cerulein-induced nuclear factor kappaB activation in both pancreas and
      lung. Also, SC treatment further enhances the beneficial effect by reducing
      cerulein-induced mast cell activation as shown by reduced monocyte
      chemoattractant protein 1, interleukin 33, and preprotachykinin A expression
      (encodes neuropeptide substance P) in the pancreas and lungs. CONCLUSIONS: The
      present findings show for the first time that in AP SC may exhibit an anti
      inflammatory effect by down-regulating substance P and hydrogen sulfide signaling
      via nuclear factor kappaB pathway.

PMID- 29595545
TI  - Where You Are Born Really Does Matter: Why Birth Hospital and Quality of Care
      Contribute to Racial/Ethnic Disparities.

PMID- 29595544
TI  - Luteolin Ameliorates Experimental Chronic Pancreatitis Induced by
      Trinitrobenzenesulfonic Acid in Rats.
AB  - OBJECTIVES: The purpose of this study is to assess the effect and possible
      mechanism of luteolin on chronic pancreatitis (CP). METHODS:
      Trinitrobenzenesulfonic acid-induced CP was used as CP models in vivo. After the
      intervention of luteolin for 28 days, chronic pancreatic injury was assessed by
      serum hydroxyproline and pancreatic histology. alpha-Smooth muscle actin (alpha
      SMA) expression was performed to detect the activation of pancreatic stellate
      cells (PSCs). Pancreatic stellate cells were also isolated and cultured in vitro,
      and the effect of luteolin on PSCs was evaluated. Transforming growth factor beta
      (TGF-beta1) signaling and its regulated mRNA expression was tested by Western
      blot and quantitative real-time polymerase chain reaction, respectively. RESULTS:
      The protective role of luteolin on CP was confirmed by increased pancreas/body
      weight ratio, decreased pancreas hydroxyproline level, and reduced fibrosis.
      alpha-SMA expressions in PSCs were significantly decreased both in vitro and in
      vivo after the management of luteolin. Pancreas TGF-beta1 expression was
      significantly decreased by luteolin. Luteolin inhibited the proliferation and
      activation of PSCs in a dose-dependent manner. CONCLUSIONS: Luteolin played a
      protective role in CP in many aspects, partly by regulating release of
      inflammatory cytokines through TGF-beta1 signaling pathway.

PMID- 29595549
TI  - Fathers' Stress in the Neonatal Intensive Care Unit: A Systematic Review.
AB  - BACKGROUND: Admission to the neonatal intensive care unit (NICU) is stressful for
      parents. Nurses often focus on maternal well-being and fail to acknowledge the
      stress of fathers. Research on fathers' psychological stress is limited. PURPOSE:
      A systematic review of the literature was completed to examine the extent of
      psychological stress and types of stressors in fathers with infants admitted to
      the NICU. METHODS/SEARCH STRATEGY: A search of Ovid MEDLINE, Cochrane Library,
      PsycINFO, CINAHL, and EMBASE was conducted to identify descriptive and
      observational studies reporting father-specific stress in the NICU. Studies using
      observational and descriptive designs, published in English, and reporting father
      specific stress outcomes during a NICU admission were eligible for inclusion.
      Strengthening the Reporting of Observational Studies in Epidemiology guidelines
      were used for quality assessment. RESULTS: Fifteen studies met inclusion
      criteria. Fathers find the NICU environment stressful and are more stressed than
      fathers of full-term, healthy infants. Parental role alteration, infant
      appearance, NICU environment, and staff communication are stressors. IMPLICATIONS
      FOR PRACTICE/RESEARCH: By recognizing the extent and types of psychological
      stress in fathers, nurses can provide better support for fathers in their new
      role. Younger fathers and those with very low birth-weight premature infants may
      need additional support and resources. Future research on fathers' stress should
      include larger sample sizes, diverse populations, and tool development and
      evaluation.

PMID- 29595550
TI  - Changing Neonatal Nurses' Perceptions of Caring for Infants Experiencing Neonatal
      Abstinence Syndrome and Their Mothers: An Evidenced-Based Practice Opportunity.
AB  - BACKGROUND: Neonatal intensive care units (NICUs) are caring for an increasing
      number of infants born with neonatal abstinence syndrome (NAS). The literature
      identifies the need for education for NICU nurses on NAS including skills for
      interacting with the mother with substance use disorder. PURPOSE: An evidence
      based practice project was developed to offer an educational presentation
      targeting these topics to 206 NICU participants (93% registered nurses, 1%
      licensed vocational nurses, and 6% nursing assistants) at a level IV NICU.
      METHODS: A pretest/posttest was developed to assess knowledge of the participants
      prior to and after completion of the educational presentation. A posteducational
      questionnaire was developed to evaluate the skills learned for interacting with
      the mother with substance use disorder and the participant's professional
      readiness. RESULTS: The posttest demonstrated a statistically significant (P <
      .001) increase in knowledge of NAS. On the post-educational questionnaire, 96% of
      participants correctly identified 3 skills they would use clinically with mothers
      with substance use disorder and 84% of participants identified 2 personal
      strengths and 2 weaknesses that influence their care of infants with NAS and
      their families (professional readiness). IMPLICATIONS FOR PRACTICE: These results
      demonstrate that this educational presentation was effective and should be
      replicated at other facilities to improve the knowledge and skills of NICU nurses
      to promote improved care for infants with NAS. IMPLICATIONS FOR RESEARCH: Future
      studies should examine the impact on patient outcomes by preforming post
      discharge interviews with the mothers of infants with NAS in the NICU pre- and
      post-educational intervention. Expanding the presentation into an
      interprofessional educational opportunity would promote increased knowledge and
      care by the entire multidisciplinary team.

PMID- 29595552
TI  - Fathers: The Lost Ring in the Chain of Family-Centered Care - A Phenomenological
      Study in Neonatal Intensive Care Units of Iran: Erratum.

PMID- 29595551
TI  - Exploring Parent Experience of Communication About Therapeutic Hypothermia in the
      Neonatal Intensive Care Unit.
AB  - BACKGROUND: The unique communication challenges faced by parents of infants
      undergoing therapeutic hypothermia have not been well characterized. PURPOSE: To
      develop awareness of communication challenges experienced by families of infants
      treated with therapeutic hypothermia. METHODS: Semistructured interviews were
      conducted in a group setting with parents matched into groups according to the
      severity of the infant's presenting encephalopathy. The interviews were
      transcribed and coded into principal and additional subthemes. RESULTS: Thirty
      adults were interviewed including 15 mothers, 12 fathers, 2 grandmothers, and 1
      grandfather. The 15 infants were between 2 and 24 months of age at the time of
      the interviews. The principal theme of communication included the following 3
      subthemes; transparency, consistency, and delivery style. Parents reported a
      strong desire for improved early and transparent communication about therapeutic
      hypothermia, particularly during transfer from an outside hospital. Parents also
      reported a preference for consistent communication and highlighted parental touch
      of the hypothermic infant, obstetrical nurse-to-neonatal intensive care unit
      nurse communication, and parent and visitor presence in the infant's room as
      areas in need of greater communication consistency. Parents valued direct and
      compassionate communication styles that excluded medical jargon. IMPLICATIONS FOR
      PRACTICE: All providers can implement recommendations for communication to
      parents of infants treated with therapeutic hypothermia by increasing
      transparency, developing greater consistency in the communication delivered, and
      employing a direct and compassionate style to improve the parental experience of
      therapeutic hypothermia. IMPLICATIONS FOR RESEARCH: Further investigation is
      needed into the specific challenges parents face with a lack of transparent
      communication prior to the transfer of an infant for therapeutic hypothermia.

PMID- 29595553
TI  - Finding My Way: A Phenomenology of Fathering in the NICU.
AB  - BACKGROUND: Historically, the relationship between infant and mother in the
      neonatal intensive care unit (NICU) has been the main focus of parenting
      research, leaving a gap in the literature regarding the paternal experience.
      PURPOSE: The purpose of this study was to gain an understanding of the lived
      experience of fathering an infant born at less than 28 weeks' gestation admitted
      to a level III NICU. METHODS: Seven fathers of premature infants (25-27 weeks'
      gestation) participated in a semistructured interview about the experience of
      becoming a father to a premature infant at least 1 to 2 weeks after the NICU
      admission. Data were collected in 2015. FINDINGS: The primary themes identified
      were looking in, persevering, holding, and finding my way. Fathers in this study
      described feeling like an outsider in the NICU while learning to trust strangers,
      protect the mother and the child, and continue to work and provide for the
      family. Holding for the first time is pivotal in this journey, as the moment of
      solidifying the connection with the child. IMPLICATIONS FOR PRACTICE: The
      findings from this study bring awareness of the experiences of fathers during the
      NICU journey of having a premature infant. Nurses should encourage paternal
      participation and involvement, visitation, and facilitate kangaroo care
      opportunities early and often. IMPLICATIONS FOR RESEARCH: The findings from this
      study allow nurses to better understand the paternal experience of having a
      premature infant born at less than 28 weeks. However, future research should
      continue to investigate the paternal experience with other gestational ages as
      well as the influence of stress of fathers during this experience.

PMID- 29595554
TI  - Fathers' Stress in the Neonatal Intensive Care Unit: A Systematic Review.

PMID- 29595556
TI  - Histopathology of Exfoliation Syndrome.
AB  - Exfoliation syndrome (XFS) is characterized by light and electron microscopy by
      age-dependent gradual accumulation of whitish material of largely unknown
      composition and origin along both the anterior and posterior chambers and widely
      within the iris stroma. These deposits can be fairly specifically labeled with
      selected antibodies and lectins. Immunohistochemistry shows that intraocular
      exfoliation deposits share antigens with the microfibrillar elastic fiber system
      and several basement membrane components, including carbohydrate epitopes on
      glycosaminoglycans, proteoglycans, and cell adhesion molecules. The earliest
      histopathologic manifestation of XFS seems to be the deposition of characteristic
      fibers in various extraocular and anterior segment tissues, as observed by
      electron microscopy, and perivascular deposition of material within the iris
      stroma, which is antigenically typical of that found in classic intraocular
      exfoliation deposits. These findings precede the clinical diagnosis of XFS and
      likewise can be detected in the seemingly uninvolved fellow eyes of patients with
      clinically unilateral XFS. Indeed, histopathologic examination of capsulotomy,
      iridectomy, and trabeculectomy specimens can lead to a clinically unexpected
      diagnosis of XFS. Exfoliation fibers are additionally found widely distributed in
      extraocular connective tissues and visceral organs, but the matrix of these
      fibers seems to differ from that of intraocular deposits. In addition to this
      histopathologic discrepancy, both the frequent occurrence of clinically
      unilateral, histopathologically highly asymmetric exfoliation deposits, and the
      relationship between the early iris vasculopathy that not infrequently may be
      observed histopathologically for years before classic widespread exfoliation
      deposits appear along the anterior and posterior chambers remain to be resolved.

PMID- 29595555
TI  - Mindfulness-Based Neurodevelopmental Care: Impact on NICU Parent Stress and
      Infant Length of Stay; A Randomized Controlled Pilot Study.
AB  - BACKGROUND/PURPOSE: Experiences of premature birth and neonatal intensive care
      unit (NICU) hospitalizations result in stress and family separation that have far
      reaching implications. Prior studies of neonatal neurodevelopmental care show
      improved infant outcomes. Previous studies of mindfulness show improved stress
      and health outcomes in varied disease processes. No neonatal studies of parent
      training in mindfulness-based neurodevelopmental care exist. This study examines
      the impact of parent education and participation in mindfulness-based
      neurodevelopmental care on parent outcomes (stress, bonding, and satisfaction)
      and infant length of stay (LOS). METHODS: This randomized controlled trial pilot
      study utilized a convenience sample of 55 parent-infant dyads. Parametric and
      nonparametric statistical tests examined differences in and between study groups
      in demographics and dependent study variables (stress, bonding, satisfaction, and
      LOS). RESULTS: No statistically significant differences in parent outcomes were
      seen between groups. However, experimental group (EG) parents showed a
      significant reduction in stress scores from enrollment to discharge (P = .012)
      and EG infants had significantly shorter LOS (P = .026-.047) than control.
      IMPLICATIONS FOR PRACTICE AND RESEARCH: While further research to confirm study
      results is warranted, changes in current NICU practices to incorporate additional
      parent education in mindfulness-based neurodevelopmental care may help alleviate
      parent stress and decrease LOS that impact financial, physical, and psychosocial
      outcomes for patients, families, healthcare systems, and society.

PMID- 29595558
TI  - Ocular Motor Dysfunction Due to Brainstem Disorders.

PMID- 29595557
TI  - Overhanging-Dissecting Blebs: Immunohistochemical Characterization.
AB  - PURPOSE: The purpose of this study was to determine if glaucoma filtering blebs
      migrate over or under the cornea epithelium using histopathologic and
      immunohistochemical techniques to evaluate the likely origin of the surface
      epithelium and bleb matrix. METHODS: Histologic and immunohistochemical
      evaluations were performed of normal conjunctiva (n=4), corneal overhanging
      dissecting blebs (n=4), and leaking blebs over the scleral surface (n=6).
      Antibodies were used against epithelial [cytokeratin 3 (CK3)+12, CK13] and
      extracellular matrix [decorin and keratan sulfate (KS)] antigens. Labeling was
      graded in a semiquantitative manner. RESULT: The epithelium of dissecting (over
      cornea) blebs was labeled primarily with CK3+12 antibody. KS staining was faint
      and comparable in normal conjunctiva, and the stroma of dissecting and leaking
      blebs (P=0.12). Decorin staining in the normal conjunctival stroma was of
      moderate intensity and comparable with the dissecting bleb staining and;
      significantly greater than that in the leaking blebs (P=0.02). CONCLUSIONS:
      Histology and ICH indicate that the epithelium of the dissecting blebs has a
      corneal epithelial phenotype. The extracellular matrix immunophenotype was
      similar to the normal conjunctival stroma suggesting that dissecting blebs
      migrate under the corneal epithelium.

PMID- 29595560
TI  - SPIRONOLACTONE AS A THERAPEUTIC ALTERNATIVE FOR THE BULLOUS VARIANT OF CENTRAL
      SEROUS CHORIORETINOPATHY.
AB  - PURPOSE: To report a case of the bullous variant of central serous
      chorioretinopathy successfully treated with spironolactone, a mineralocorticoid
      receptor antagonist. METHODS: Case report of a patient including fluorescein
      angiography, optical coherence tomography, and color fundus photography. RESULTS:
      Initially managed as a multifocal choroiditis, the use of oral and peribulbar
      corticoids worsened the serous retinal detachment. Taking in consideration this
      response, she was then diagnosed with a bullous variant of central serous
      chorioretinopathy and treated with 50 mg of spironolactone per day. Resolution of
      the serous retinal detachment, decrease in choroidal thickness on optical
      coherence tomography, and absence of leaks in fluorescein angiography was
      achieved 2 months posterior to the first dose of oral spironolactone. CONCLUSION:
      We suggest the use of mineralocorticoid receptor antagonists, such as
      spironolactone, as a therapeutic alternative to more aggressive available
      treatments for the bullous variant of central serous chorioretinopathy.

PMID- 29595559
TI  - MTHFR gene methylation is associated with perceived stress in healthy young
      adults.
AB  - BACKGROUND: Epigenetic factors have been identified in the past years as
      interesting candidates for psychiatric disorders and related endophenotypes. It
      has been found that the methylenetetrahydrofolate reductase (MTHFR) gene is
      associated with major depressive disorder, and the aim of the current study was
      to examine the possible association between perceived stress and MTHFR
      methylation, taking into account depressive symptoms as a covariate. PARTICIPANTS
      AND METHODS: Seventy-eight healthy Colombian participants (mean age=20.9 years;
      SD=3.0) were evaluated with the Perceived Stress Scale and with the Patient
      Health Questionnaire-9 for depressive symptomatology. MTHFR methylation levels
      were measured with a methylation-sensitive high-resolution melting method. A
      multiple regression analysis (adjusting for age, sex, and depressive symptoms)
      was carried out to assess the association between MTHFR methylation and perceived
      stress scores. RESULTS: We found a significant inverse correlation between MTHFR
      methylation levels and perceived stress scores (r=-0.502; P=5.9*10(-5)), which
      remained significant after being adjusted for age, sex, and depressive
      symptomatology. CONCLUSION: To our knowledge, this is the first study that
      reports an association between perceived stress and MTHFR methylation levels.
      This report adds evidence to the emerging role of epigenetic changes in
      endophenotypes related to affective disorders.

PMID- 29595561
TI  - Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After
      Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis
      Model.
AB  - OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin
      liberation and inflammatory response in vivo in a clinically relevant large
      animal intensive care sepsis model and whether the addition of an aminoglycoside
      to a beta-lactam antibiotic affects these responses. DESIGN: Prospective, placebo
      controlled interventional experimental study. SETTING: University research unit.
      SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour
      infusion. INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were
      exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or
      saline. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor
      necrosis factor-alpha, leucocytes, and organ dysfunction were recorded for 4
      hours after antibiotic treatment, and differences to the values before treatment
      were calculated. In vitro experiments were performed to ascertain whether
      endotoxin is released during antibiotic-induced bacterial killing of this E. coli
      strain. Despite differences between the treatment arms in vitro, no differences
      in plasma endotoxin were observed in vivo. Antibiotic-treated animals
      demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte
      activation (p < 0.001), and more pronounced deterioration in pulmonary static
      compliance (p < 0.01) over time than controls. Animals treated with the
      combination showed a trend toward less inflammation. CONCLUSIONS: Treatment with
      antibiotics may elicit an increased inflammatory interleukin-6 response that is
      associated with leucocyte activation and pulmonary organ dysfunction. No
      observable differences were detected in plasma endotoxin concentrations. The
      reduction in cefuroxime-induced endotoxin release after the addition of an
      aminoglycoside in vitro could not be reproduced in this model.

PMID- 29595562
TI  - Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the
      Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial.
AB  - OBJECTIVES: Occurrence of delirium in the ICU is associated with a longer stay in
      the ICU. To examine whether the use of ramelteon, a melatonin agonist, can
      prevent delirium and shorten the duration of ICU stay of critically ill patients.
      DESIGN: A single-center, triple-blinded, randomized placebo-controlled trial.
      SETTING: ICU of an academic hospital. PATIENTS: Eligible patients were ICU
      patients who could take medicines orally or through a nasogastric tube during the
      first 48 hours of admission. INTERVENTIONS: The intervention group received
      ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose
      powder) at 20:00 hours every day until discharge from the ICU. MEASUREMENTS AND
      MAIN RESULTS: A total of 88 subjects were randomized to the ramelteon group (45
      subjects) or the placebo group (43 subjects). As the primary endpoint, there was
      a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon
      group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before
      and after adjustments). As the secondary endpoints, statistically significant
      decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78
      vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The
      nonintubated patients of the ramelteon group showed statistically significantly
      fewer awakenings per night and a higher proportion of nights without awakenings.
      CONCLUSIONS: Ramelteon tended to decrease the duration of ICU stay as well as
      decreased the occurrence rate and duration of delirium statistically
      significantly.

PMID- 29595564
TI  - Synergizing With Teacher Educators to Provide Peer Evaluations for Nursing
      Faculty.

PMID- 29595563
TI  - One-Year Outcomes in Patients With Acute Respiratory Distress Syndrome Enrolled
      in a Randomized Clinical Trial of Helmet Versus Facemask Noninvasive Ventilation.
AB  - OBJECTIVES: Many survivors of acute respiratory distress syndrome have poor long
      term outcomes possibly due to supportive care practices during "invasive"
      mechanical ventilation. Helmet noninvasive ventilation in acute respiratory
      distress syndrome may reduce intubation rates; however, it is unknown if avoiding
      intubation with helmet noninvasive ventilation alters the consequences of
      surviving acute respiratory distress syndrome. DESIGN: Long-term follow-up data
      from a previously published randomized controlled trial. PATIENTS: Adults
      patients with acute respiratory distress syndrome enrolled in a previously
      published clinical trial. SETTING: Adult ICU. INTERVENTION: None. MEASUREMENTS
      AND MAIN RESULTS: The primary outcome was functional independence at 1 year after
      hospital discharge defined as independence in activities of daily living and
      ambulation. At 1 year, patients were surveyed to assess for functional
      independence, survival, and number of institution-free days, defined as days
      alive spent living at home. The presence of ICU-acquired weakness and functional
      independence was also assessed by a blinded therapist on hospital discharge. On
      hospital discharge, there was a greater prevalence of ICU-acquired weakness
      (79.5% vs 38.6%; p = 0.0002) and less functional independence (15.4% vs 50%; p =
      0.001) in the facemask group. One-year follow-up data were collected for 81 of 83
      patients (97.6%). One-year mortality was higher in the facemask group (69.2% vs
      43.2%; p = 0.017). At 1 year, patients in the helmet group were more likely to be
      functionally independent (40.9% vs 15.4%; p = 0.015) and had more institution
      free days (median, 268.5 [0-354] vs 0 [0-323]; p = 0.017). CONCLUSIONS: Poor
      functional recovery after invasive mechanical ventilation for acute respiratory
      distress syndrome is common. Helmet noninvasive ventilation may be the first
      intervention that mitigates the long-term complications that plague survivors of
      acute respiratory distress syndrome managed with noninvasive ventilation.

PMID- 29595565
TI  - Factors Influencing Part-time Faculty Engagement With Online Nursing Programs.
AB  - This research investigated factors that influenced the engagement of part-time
      faculty teaching in online nursing programs with their institutions. Of the 257
      part-time faculty surveyed, the most significant factor was being supported in
      decisions regarding student issues, followed by institutional commitment to
      quality online education. Compensation was moderately influential; a negative
      factor was requiring too frequent meetings. Understanding factors that influence
      the engagement of part-time faculty teaching in online nursing programs can help
      leaders of online programs attract and retain experienced, highly skilled
      faculty.

PMID- 29595566
TI  - Student Perceptions of Peer Evaluation in an Online RN-to-BSN Course.
AB  - The purpose of this study was to explore student perceptions of peer-evaluation
      experiences in an online RN-to-BSN nursing research course. A total of 140
      students completed the online survey. A majority of students reported their peer
      evaluation experience was helpful for learning (69%), and 81.8% of students
      indicated their writing skills improved. Findings of the study support the use of
      peer evaluation in online nursing courses.

PMID- 29595567
TI  - Integrating Climate Change Into Nursing Curricula.
AB  - Climate change is a significant threat to human health across the life cycle.
      Nurses play an important role in mitigation, adaptation, and resilience to
      climate change. The use of health care resources, air quality and extreme heat,
      mental health, and natural disasters are major content areas across undergraduate
      nursing curricula that influence or are influenced by climate change. Teaching
      strategies and resources are offered to prepare nursing students to address
      climate change and human health.

PMID- 29595568
TI  - Hotspotting: Development of an Interprofessional Education and Service Learning
      Program for Care Management in Home Care Patients.
AB  - The purpose of this article is to describe a service learning opportunity where
      interprofessional teams of students worked together to address patients' social
      determinants of health through home visits. This article describes this process,
      known as "hotspotting," and presents the development of this project, including
      collaboration with a local home health agency, recruiting of students, and weekly
      team meetings for debriefing. Evaluation data, barriers with implementation, and
      next steps for sustainability are also discussed.

PMID- 29595569
TI  - SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS AND VISUAL OUTCOME AFTER
      TREATMENT FOR VITREOMACULAR TRACTION.
AB  - PURPOSE: To evaluate the capacity of spectral domain optical coherence tomography
      macular findings to predict best-corrected visual acuity (BCVA) outcomes after
      treatment for symptomatic vitreomacular traction. METHODS: This consecutive,
      retrospective study included 24 patients (29 eyes) who experienced vitreomacular
      traction release with pneumatic vitreolysis (n = 9), intravitreal ocriplasmin (n
      = 6), or pars plana vitrectomy (n = 14). Preoperative and postoperative spectral
      domain optical coherence tomography images were used to determine the cone outer
      segment tips (COST) line, inner segment/outer segment line, and other frequently
      used features. Correlations between optical coherence tomography findings and
      BCVA were determined using regression analyses. RESULTS: Postoperative BCVA was
      correlated with length of the COST line and inner segment/outer segment line
      defects at 1, 3, 6, and 12 months postoperatively (P < 0.05) by simple linear
      regression analysis. However, multivariable regression analysis showed that only
      length of the COST line defect was significantly correlated with BCVA
      preoperatively and postoperatively (P < 0.05). Postoperative BCVA improvement at
      12 months was significantly correlated with preoperative length of the COST line
      defect (P < 0.01). CONCLUSION: Recovery of the COST line and inner segment/outer
      segment line defects as observed by spectral domain optical coherence tomography
      is positively correlated with visual acuity improvement after successful
      vitreomacular traction treatment. Best-corrected visual acuity improvement may be
      predicted using the length of the preoperative COST line defect.

PMID- 29595570
TI  - Reply.

PMID- 29595571
TI  - Targeted ultrasound and fine-needle aspiration cytology for sentinel node
      diagnostics in early-stage melanoma: a validation study.
AB  - Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is used to evaluate
      the involvement of lymph nodes in various malignant diseases. Its value in
      detecting sentinel lymph node (SN) metastasis preoperatively in melanoma patients
      is controversial and is the subject of this study. In this prospective validation
      study, 91 consecutive patients with melanoma clinical stage I (n=64) and II
      (n=27) were examined with US-FNAC before SN biopsy from 2012 to 2014 at a
      tertiary center. All patients underwent lymphoscintigraphy before the US-FNAC.
      Lymph nodes that showed any of the Berlin morphologic criteria on ultrasonography
      were examined using FNAC. The median Breslow thickness of the melanomas was 1.22
      mm (range: 0.47-11.5 mm). Twenty-two percent of the patients had metastases in
      their SNs, 90% of which were smaller than 2 mm in largest diameter. The
      percentages of metastases with a size more than 1 mm were 50 and 29%,
      respectively, in the true-positive and false-negative US groups. The sensitivity,
      specificity, positive predictive value, and negative predictive value for overall
      US examination were 30, 81, 24, and 83%, respectively. None of the FNACs
      contained conclusive malignant cells. The specificity of the FNAC was 76%. Our
      results show that US-FNAC was not a useful diagnostic tool in our setting as it
      did not add significantly to the staging and management of patients with mainly
      thin cutaneous melanomas, perhaps because of the often small size of the SN
      metastases. It may be useful in the early diagnosis of lymph node metastases in a
      subgroup of melanoma patients with larger metastases.

PMID- 29595572
TI  - Transforming Government Health Data Into All-Star Open Data: Benchmarking Data
      Quality.

PMID- 29595573
TI  - Public Health Resilience Checklist for High-Consequence Infectious Diseases
      Informed by the Domestic Ebola Response in the United States.
AB  - CONTEXT: The experiences of communities that responded to confirmed cases of
      Ebola virus disease in the United States provide a rare opportunity for
      collective learning to improve resilience to future high-consequence infectious
      disease events. DESIGN: Key informant interviews (n = 73) were conducted between
      February and November 2016 with individuals who participated in Ebola virus
      disease planning or response in Atlanta, Georgia; Dallas, Texas; New York, New
      York; or Omaha, Nebraska; or had direct knowledge of response activities.
      Participants represented health care; local, state, and federal public health;
      law; local and state emergency management; academia; local and national media;
      individuals affected by the response; and local and state governments. Two focus
      groups were then conducted in New York and Dallas, and study results were vetted
      with an expert advisory group. RESULTS: Participants focused on a number of
      important areas to improve public health resilience to high-consequence
      infectious disease events, including governance and leadership, communication and
      public trust, quarantine and the law, monitoring programs, environmental
      decontamination, and waste management. CONCLUSIONS: Findings provided the basis
      for an evidence-informed checklist outlining specific actions for public health
      authorities to take to strengthen public health resilience to future high
      consequence infectious disease events.

PMID- 29595574
TI  - Federal Weatherization and Health Education Team up: Process Evaluation of a New
      Strategy to Improve Health Equity for People With Asthma and Chronic Obstructive
      Pulmonary Disease.
AB  - Unhealthy housing is a major cause of respiratory health inequity. In-home health
      education improves health equity for low-income and minority populations with
      asthma and chronic obstructive pulmonary disease. Yet, outcomes of educational
      interventions are limited by poor housing conditions. Federal weatherization
      programs represent a promising source of funding for home repairs. Innovative
      legislation in Washington State integrates the 2 interventions as "Weatherization
      Plus Health," offering environmental health education in partnership with the
      Weatherization Assistance Program for low-income families with respiratory
      disease. This practice brief describes process evaluation results of a
      Weatherization Plus Health program in Pierce County, Washington. Evaluation data
      were gathered via interviews with service providers and ethnographic observation.
      Workers report that the combined intervention expanded their understanding of
      their practice, skills, and feelings of efficacy in meeting client needs.
      Integrating federally funded home weatherization with health education shows
      promise for building public health system capacity and increasing health equity.

PMID- 29595575
TI  - Retrospective Evaluation of the Short-Term Sustainability of the Locally Grown
      Produce Initiative of the Hunger Prevention and Nutrition Assistance Program in
      New York State.
AB  - CONTEXT: The Hunger Prevention and Nutrition Assistance Program (HPNAP) is a New
      York State Department of Health program. The HPNAP improves nutritional quality
      of food available at food banks, food pantries, soup kitchens, and emergency
      shelters through contractual relationships to fund the purchase, delivery,
      storage, and service of nutritious food. OBJECTIVE: To determine whether a one
      time fiscal stimulus of the Locally Grown Produce Initiative to HPNAP contractors
      in 2012-2013 would result in a short-term sustainable increase in the proportion
      of dollars spent on New York State Grown (NYSG) produce. DESIGN: Quasi
      experimental, nonequivalent control group design. We analyzed New York State
      Department of Health administrative data regarding expenditures on all produce
      and NYSG produce by HPNAP contractors. SETTING: New York State. OUTCOME MEASURES:
      The proportion of dollars spent on NYSG produce during 2011-2012
      (preintervention) and 2013-2014 (postintervention) was compared between HPNAP
      food bank contractors (recipients of stimulus money, n = 8) and non-food bank
      contractors (nonrecipients, n = 34) using nonparametric methods. RESULTS: The
      HPNAP Locally Grown Produce Initiative was associated with an increased
      proportion of NYSG produce spending by food bank contractors that received a
      fiscal stimulus 1 year later. Upstate food banks had the largest increase (median
      31.6%) among all HPNAP contractors. CONCLUSION: The results of this study
      revealed that the Locally Grown Produce Initiative fiscal stimulus had a
      positive, year-long and statewide effect on the proportion of expenditure on NYSG
      produce by food banks. We hope that the initial success seen in New York State
      may encourage other states to adopt similar initiatives in future.

PMID- 29595576
TI  - Leadership Perceptions of Endgame Strategies for Tobacco Control in California.
AB  - OBJECTIVE: To explore the perspectives of key stakeholders regarding advancement
      of the tobacco endgame in California. DESIGN: Interviews and focus groups
      exploring participants' knowledge of the tobacco endgame concept, their reactions
      to 4 endgame policy proposals (banning tobacco sales, registering smokers,
      retailer reduction, and permanently prohibiting tobacco sales to all those born
      after a certain year ["tobacco-free generation"]), and policy priorities and
      obstacles. PARTICIPANTS: Interviews with 11 California legislators/legislative
      staff members, 6 leaders of national tobacco control organizations, and 5 leaders
      of California-based organizations or California subsidiaries of national
      organizations. Focus groups (7) with professional and volunteer tobacco control
      advocates in Northern, Southern, and Central California. RESULTS: Advocates were
      more familiar with the endgame concept than legislators or legislative staff. All
      proposed endgame policies received both support and opposition, but smoker
      registration and banning tobacco sales were the least popular, regarded as too
      stigmatizing or too extreme. The tobacco-free generation and retailer-reduction
      policies received the most support. Both were regarded as politically feasible,
      given their focus on protecting youth or regulating retailers and their gradual
      approach. Concerns raised about all the proposals included the creation of black
      markets and the potential for disparate impacts on disadvantaged communities.
      CONCLUSION: Participants' willingness to support novel tobacco control proposals
      suggests that they understand the magnitude of the tobacco problem and have some
      appetite for innovation despite concerns about specific endgame policies. A
      preference for more gradual approaches suggests that taking incremental steps
      toward an endgame policy goal may be the most effective strategy.

PMID- 29595577
TI  - What Is the Appropriate Role of Interprofessional Education in Public Health?

PMID- 29595578
TI  - A Menu to Evaluate Factors Influencing Implementation of Obesity Prevention Early
      Care and Education Regulations.
AB  - CONTEXT: In recent years, several states have adopted new regulations concerning
      nutrition, physical activity, and screen time in early care and education (ECE)
      settings to help prevent childhood obesity. OBJECTIVE: To disseminate a menu of
      factors that facilitate and/or impede implementation of obesity prevention
      regulations in ECE settings. DESIGN: To create the menu, we condensed and
      categorized factors identified in the literature and through field work by
      placing them within domains. We applied the menu by conducting semistructured
      interviews during a pilot test assessing implementation of ECE regulations in
      Colorado. SETTING AND PARTICIPANTS: We first interviewed state and local
      government agency leaders responsible for policy oversight, and state employees
      and contractors who acted as intermediaries to direct implementers. We then
      interviewed directors at ECE centers in the Denver, Colorado, area. We selected
      21 ECE centers for a site visit on the basis of feasibility, percentage of low
      income families, and diversity in race and ethnicity at each center. Seven
      centers participated. MAIN OUTCOME MEASURES: Minor and major facilitators and
      impediments to implementation of childhood obesity prevention regulations in ECE
      settings. RESULTS: The resulting menu includes 7 domains and 39 factors
      influential for implementation of ECE regulations. Of these 39 factors,
      interviewees identified 7 facilitating factors (4 major and 3 minor) and 2
      impeding factors (both major). Major facilitating factors were buy-in from
      parents/caregivers, training and communication provided by governing authority
      and their contractors, and low level of change required by the regulations
      themselves. Major impeding factors were timing of implementation and balancing
      the demands of the regulations against other priorities. CONCLUSIONS: The menu
      developed by our research team, combined with existing frameworks in
      dissemination and implementation research, can be used by researchers,
      practitioners, and policy makers to anticipate factors that facilitate and/or
      impede implementation of ECE policies to prevent childhood obesity.

PMID- 29595579
TI  - Prevention of Otic Barotrauma in Aviation: A Systematic Review.
AB  - OBJECTIVE: To conduct a systematic review of the published evidence relating to
      the prevention of otic barotrauma in aviation. In particular, this review sought
      to identify procedures, techniques, devices, and medications for the prevention
      of otic barotrauma as well as evaluate the evidence relating to their efficacy.
      DATA SOURCES: Ten databases including Embase, MEDLINE, the Cochrane Database of
      Systematic Reviews, and the Cochrane Central Register of Controlled Trials were
      searched using the full historical range. STUDY SELECTION: English language
      articles including more than or equal to five participants or cases were
      included. Outcomes of interest were reduced severity or the successful prevention
      of otic barotrauma in participants undergoing gradual changes in pressure during
      air travel or its simulation. DATA EXTRACTION: Articles and data were extracted
      and analyzed according to Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses and other international guidelines. CONCLUSIONS: This review
      highlights the lack of published evidence relating to what is a significant and
      increasingly common problem in otology. There is level 1 evidence that supports
      the efficacy of oral pseudoephedrine (120 mg) in preventing otic barotrauma in
      adults. However, oral pseudoephedrine (1 mg/kg) does not appear to be effective
      in children. There is insufficient evidence to support the efficacy of either
      nasal balloon inflation or pressure-equalizing ear plugs for the prevention of
      otic barotrauma. A recently reported, novel technique for insertion of temporary
      tympanostomy tubes is promising but requires further evaluation.

PMID- 29595581
TI  - Reconstruction of the Canal Wall in Tympanoplasty for Cholesteatoma With Titanium
      Sheeting.

PMID- 29595580
TI  - The Use of Vibrotactile Feedback During Dual-Task Standing Balance Conditions in
      People With Unilateral Vestibular Hypofunction.
AB  - HYPOTHESIS: People with unilateral vestibular hypofunction (UVH) would have
      increased postural sway and slower reaction times while using vibrotactile
      feedback (VTF) during dual-task conditions compared with age-matched controls.
      BACKGROUND: VTF has been shown to improve real-time balance performance in
      persons with vestibular disorders. Future use of this technology outside of the
      laboratory environment as a real-time balance aid requires that using VTF during
      dual-tasking scenarios be studied. METHOD: Nine people with UVH and nine age
      matched controls participated in a study focused on assessing the effects of a
      secondary cognitive task and sensory integration conditions on the root-mean
      square of center of pressure (RMS COP) while using VTF. Reaction times from the
      secondary cognitive task were used to assess the effects of VTF, and sensory
      integration conditions on the attention required to perform the task. RESULTS:
      The results showed that there was no group difference between individuals with
      UVH and age-matched controls on balance performance while using VTF during dual
      task conditions. Using VTF significantly degraded the reaction time performance
      in both groups, and the participants with UVH had slower reaction times compared
      with controls. CONCLUSION: People with UVH showed the ability to use VTF to
      control balance during dual-task conditions, but more attentional resources were
      needed to perform the secondary cognitive tasks while using VTF.

PMID- 29595582
TI  - Burkitt Lymphoma of the Temporal Bone.

PMID- 29595583
TI  - Gait Variability and Energy Cost of Oveground Walking in Persons With Multiple
      Sclerosis: A Cross-Sectional Study.
AB  - OBJECTIVE: This study examined the associations between gait variability based on
      common spatiotemporal parameters and energetic cost of walking in persons with
      multiple sclerosis. DESIGN: Eighty-six persons with multiple sclerosis underwent
      the 6-min walk while wearing a portable metabolic unit. The cost of walking was
      generated by dividing the net steady-state VO2 (milliliter per kilogram per
      minute) by walking speed during the 6-min walk. Participants further completed
      two trials of walking on the GAITRite mat at a self-selected pace for measuring
      spatiotemporal parameters. Variability of step length, step time, stride length,
      swing time, stance time, stride velocity, and single- and double-support time was
      indexed by the coefficient of variation. RESULTS: Variability in the
      spatiotemporal variables and Expanded Disability Status Scale scores were
      significantly correlated with cost of walking (i.e., rho = 0.25-0.36).
      Multivariate analysis revealed that disability (Expanded Disability Status Scale:
      beta = 0.186), stance time variability (beta = 1.446), and step length
      variability (beta = -1.216) explained significant variance (R = 0.38, P < 0.001)
      in cost of walking. CONCLUSIONS: We provide evidence of the positive association
      between gait variability and cost of walking during overground walking in persons
      with multiple sclerosis. The findings highlight the need for interventions aiming
      to reduce gait variability, thereby reducing the energetic demands of walking in
      this population.

PMID- 29595585
TI  - The Efficiency of a Multicomponent Training for Prospective Memory Among Healthy
      Older Adults: A Single-Blind, Randomized Controlled Within-Participants Cross
      Over Trial.
AB  - OBJECTIVE: The main objective of the present trial was to evaluate the efficiency
      of a preventative multicomponent prospective memory training among healthy older
      adults. DESIGN: This study was a two-arm within-participants trial with 4- and 12
      wk follow-ups. Allocation ratio was 1:1, and pretraining and posttraining
      measurements were included. A total number of 25 healthy older adults were
      enrolled (mean = 63.32, SD = 4.44). Participants were randomly allocated into two
      conditions: (a) prospective memory training: participants underwent a
      multicomponent prospective memory training, and (b) control: participants were
      not contacted during the training phase. After the training phase was finished,
      participants crossed over to undergo the condition they did not experience
      before. The differences between pretraining and posttraining measures of
      prospective memory, activities of daily living, negative mood (depression), and
      anxiety were assessed. All changes in the measurements were analyzed using
      general linear method. This trial is registered at https://www.isrctn.com
      (#ISRCTN57600070). RESULTS: Multicomponent prospective memory training program
      was significantly effective on both subjective and objective prospective memory
      performances among healthy older adults. Moreover, the training had significant
      positive effects on activities of daily living (independence) among participants.
      In addition, negative mood and anxiety levels were reduced after the training was
      finished. CONCLUSIONS: This multicomponent prospective memory training improved
      prospective memory performance and activities of daily living and reduce negative
      mood (depression) and anxiety levels among healthy older adults.

PMID- 29595584
TI  - Discharge Patterns for Ischemic and Hemorrhagic Stroke Patients Going From Acute
      Care Hospitals to Inpatient and Skilled Nursing Rehabilitation.
AB  - OBJECTIVE: The aim of the study was to explore variation in acute care use of
      inpatient rehabilitation facilities and skilled nursing facilities rehabilitation
      after ischemic and hemorrhagic stroke. DESIGN: A secondary analysis of Medicare
      claims data linked to inpatient rehabilitation facilities and skilled nursing
      facilities assessment files (2013-2014) was performed. RESULTS: The sample
      included 122,084 stroke patients discharged to inpatient or skilled nursing
      facilities from 3677 acute hospitals. Of the acute hospitals, 3649 discharged
      patients with an ischemic stroke (range = 1-402 patients/hospital, median = 15)
      compared with 1832 acute hospitals that discharged patients with hemorrhagic
      events (range = 1-73 patients/hospital, median = 4). The intraclass correlation
      coefficient examined variation in discharge settings attributed to acute
      hospitals (ischemic intraclass correlation coefficient = 0.318, hemorrhagic
      intraclass correlation coefficient = 0.176). Patients older than 85 yrs and those
      with greater numbers of co-morbid conditions were more likely to discharge to
      skilled nursing facilities. Comparison of self-care and mobility across stroke
      type suggests that patients with ischemic stroke have higher functional abilities
      at admission. CONCLUSIONS: This study suggests demographic and clinical
      differences among stroke patients admitted for postacute rehabilitation at
      inpatient rehabilitation facilities and skilled nursing facilities settings.
      Furthermore, examination of variation in ischemic and hemorrhagic stroke
      discharges suggests acute facility-level differences and indicates a need for
      careful consideration of patient and facility factors when comparing the
      effectiveness of inpatient rehabilitation facilities and skilled nursing
      facilities rehabilitation.

PMID- 29595586
TI  - The Search for Elusive Progress Against the Epidemic of Childhood Obesity.

PMID- 29595587
TI  - Public Health Informatics Incubators: Accelerating Innovation Through Creative
      Partnerships Between Informatics Experts and Public Health Agencies.

PMID- 29595588
TI  - A Uniform Chart of Accounts for Public Health Agencies: An "Essential Ingredient"
      for a Strong Public Health System.

PMID- 29595589
TI  - Advancing Trauma Center Injury and Violence Prevention: Public Health and Health
      Care Working Together.

PMID- 29595590
TI  - The Impact of Public Health Department Accreditation: 10 Years of Lessons
      Learned.

PMID- 29595591
TI  - Quality Improvement and Performance Management Benefits of Public Health
      Accreditation: National Evaluation Findings.
AB  - OBJECTIVE: To identify the quality improvement (QI) and performance management
      benefits reported by public health departments as a result of participating in
      the national, voluntary program for public health accreditation implemented by
      the Public Health Accreditation Board (PHAB). DESIGN: We gathered quantitative
      data via Web-based surveys of all applicant and accredited public health
      departments when they completed 3 different milestones in the PHAB accreditation
      process. PARTICIPANTS: Leadership from 324 unique state, local, and tribal public
      health departments in the United States. RESULTS: Public health departments that
      have achieved PHAB accreditation reported the following QI and performance
      management benefits: improved awareness and focus on QI efforts; increased QI
      training among staff; perceived increases in QI knowledge among staff;
      implemented new QI strategies; implemented strategies to evaluate effectiveness
      and quality; used information from QI processes to inform decision making; and
      perceived achievement of a QI culture. The reported implementation of QI
      strategies and use of information from QI processes to inform decision making was
      greater among recently accredited health departments than among health
      departments that had registered their intent to apply but not yet undergone the
      PHAB accreditation process. Respondents from health departments that had been
      accredited for 1 year reported higher levels of staff QI training and perceived
      increases in QI knowledge than those that were recently accredited. CONCLUSIONS:
      PHAB accreditation has stimulated QI and performance management activities within
      public health departments. Health departments that pursue PHAB accreditation are
      likely to report immediate increases in QI and performance management activities
      as a result of undergoing the PHAB accreditation process, and these benefits are
      likely to be reported at a higher level, even 1 year after the accreditation
      decision.

PMID- 29595592
TI  - Has Voluntary Public Health Accreditation Impacted Health Department Perceptions
      and Activities in Quality Improvement and Performance Management?
AB  - CONTEXT: The Public Health Accreditation Board (PHAB) is now in its 10th year,
      making it an ideal time to study the impact of PHAB accreditation on local health
      departments (LHDs). OBJECTIVE: To examine whether applying for PHAB accreditation
      affects perceptions and activities regarding quality improvement (QI) and
      performance management (PM) within LHDs. DESIGN: Data from the National
      Association of County & City Health Officials' 2010, 2013, and 2016 National
      Profile of Local Health Departments and associated QI modules were linked to PHAB
      applicant data collected in e-PHAB in a cross-sectional and longitudinal approach
      examining self-reported QI/PM activities. PARTICIPANTS: Local health departments
      responding to National Association of County & City Health Officials Profile
      questionnaires and QI modules in 2010, 2013, and 2016. MAIN OUTCOME MEASURES:
      Implementation of formal QI program within agency, numbers of formal QI projects
      in the past year, presence of elements indicating formal QI program
      implementation, and changes over time by accreditation status as of June 2017.
      RESULTS: Accredited and in-process LHDs showed greater gains over time in all of
      the outcome measures than LHDs not registered in e-PHAB. Results of logistic
      regression controlling for population served and governance type found accredited
      LHDs more likely to report formal QI programs agency-wide (odds ratio: [OR] =
      27.0; P < .001) and have implemented 6 to 8 elements of formal QI (OR = 27.0; P <
      .001) in 2016, compared with nonaccreditation-seeking LHDs. Between 2013 and
      2016, LHDs that responded to both survey waves that were registered in e-PHAB or
      accredited were significantly more likely than nonaccreditation-seeking LHDs to
      report any increase in overall level of QI implementation (OR = 4.89; P = .006)
      and increase in number of elements of formal QI (OR = 16.1; P < .001).
      CONCLUSIONS: Local health departments accredited by June 2017 and those in
      process reported more formal QI activities and showed greater improvements with
      QI/PM implementation over time than LHDs not undertaking accreditation. Public
      Health Accreditation Board accreditation appears to influence QI/PM uptake. As
      health departments are contemplating whether to apply for accreditation, the
      potential for developing a more robust QI/PM system should be taken into account.

PMID- 29595593
TI  - Public Health Accreditation Impact: The Performance Management System.

PMID- 29595594
TI  - Clackamas County Public Health: Employee Engagement in Quality Improvement and
      Performance Management Activities.
AB  - This case report provides an example of a local health department's use of
      performance management tools across its agency. An emphasis is on engaging staff
      across all levels of the organization so that employees can understand how their
      work affects overall performance management.

PMID- 29595595
TI  - Changes in Local Public Health System Performance Before and After Attainment of
      National Accreditation Standards.
AB  - OBJECTIVE: The aim of this study is to investigate the impact of Public Health
      Accreditation Board (PHAB) accreditation on the delivery of public health
      services and on participation from other sectors in the delivery of public health
      services in local public health systems. DESIGN: This study uses a longitudinal
      repeated measures design to identify differences between a cohort of public
      health systems containing PHAB-accredited local health departments and a cohort
      of public health systems containing unaccredited local health departments. It
      uses data spanning from 2006 to 2016. SETTING: This study examines a cohort of
      local public health systems that serves large populations and contains
      unaccredited and PHAB-accredited local health departments. PARTICIPANTS: Data in
      this study were collected from the directors of health departments that include
      local public health systems followed in the National Longitudinal Study of Public
      Health Systems. INTERVENTION: The intervention examined is PHAB accreditation.
      MAIN OUTCOME MEASURES: The study focuses on 4 areas: the delivery of core public
      health services, local health department contribution toward these services,
      participation in the delivery of these services by other members of the public
      health system, and public health system makeup. RESULTS: Prior to the advent of
      accreditation, public health systems containing local health departments that
      were later accredited by PHAB appear quite similar to their unaccredited peers.
      Substantial differences between the 2 cohorts appear to manifest themselves after
      the advent of accreditation. Specifically, the accredited cohort seems to offer a
      broader array of public health services, involve more partners in the delivery of
      those services, and enjoy a higher percentage of comprehensive public health
      systems. CONCLUSIONS: The results of this study suggest that accreditation may
      yield significant benefits and may help public health systems develop the public
      health system capital necessary to protect and promote the public's health.

PMID- 29595596
TI  - Accredited Health Department Partnerships to Improve Health: An Analysis of
      Community Health Assessments and Improvement Plans.
AB  - CONTEXT: The Public Health Accreditation Board (PHAB) Standards & Measures
      require the development and updating of collaborative community health
      assessments (CHAs) and community health improvement plans (CHIPs). OBJECTIVE: The
      goal of this study was to analyze the CHAs and CHIPs of PHAB-accredited health
      departments to identify the types of partners engaged, as well as the objectives
      selected to measure progress toward improving community health. DESIGN: The study
      team extracted and coded data from documents from 158 CHA/CHIP processes
      submitted as part of the accreditation process. Extracted data included
      population size, health department type, data sources, and types of partner
      organizations. Health outcome objectives were categorized by Healthy People 2020
      Leading Health Indicator (LHI), as well as by the 7 broad areas in the PHAB
      reaccreditation framework for population health outcomes reporting. PARTICIPANTS:
      Participants included health departments accredited between 2013 and 2016 that
      submitted CHAs and CHIPs to PHAB, including 138 CHAs/CHIPs from local health
      departments and 20 from state health departments. RESULTS: All the CHAs/CHIPs
      documented collaboration with a broad array of partners, with hospitals and
      health care cited most frequently (99.0%). Other common partners included
      nonprofit service organizations, education, business, and faith-based
      organizations. Small health departments more frequently listed many partner
      types, including law enforcement and education, compared with large health
      departments. The majority of documents (88.6%) explicitly reference Healthy
      People 2020 goals, with most addressing the LHIs nutrition/obesity/physical
      activity and access to health services. The most common broad areas from PHAB's
      reaccreditation framework were preventive health care and individual behavior.
      CONCLUSIONS: This study demonstrates the range of partners accredited health
      departments engage with to collaborate on improving their communities' health as
      well as the objectives used to measure community health improvement. This
      illustrates the collaborative nature in which accredited health departments
      tackle community priorities.

PMID- 29595597
TI  - Working Together for Healthy People and Sustainable Communities: A Commentary on
      How the Alignment of Public Health Standards and Sustainable Communities
      Certification Can Lead to Improvements in Quality of Life for All.

PMID- 29595598
TI  - Are Public Health Academia, Professional Certification, and Public Health
      Practice on the Same Page?

PMID- 29595599
TI  - Public Health Accreditation and Collaborative Partnerships.

PMID- 29595600
TI  - How Can Health Departments Better Serve Populations With Intellectual
      Disabilities?

PMID- 29595601
TI  - Public Health Accreditation: History, Implications, and Opportunities for Tribal
      Public Health.

PMID- 29595602
TI  - How Public Health Accreditation Helped One Local Health Department Integrate and
      Promote Health Equity.

PMID- 29595603
TI  - Ohio Statewide Efforts to Align Public Health/Health Care Population Health
      Planning.

PMID- 29595604
TI  - Using Quality Improvement to Improve Internal and External Coordination and
      Referrals.
AB  - As part of accreditation, Public Health Accreditation Board site visitors
      recommended that the New Orleans Health Department strengthen its quality
      improvement program. With support from the Public Health Accreditation Board, the
      New Orleans Health Department subsequently embarked on a data-driven planning
      process through which it prioritized quality improvement projects for 2016. One
      of these projects aimed to improve referrals to New Orleans Health Department's
      direct services programs from local clinics and hospitals to better provide our
      most vulnerable residents with a continuum of care. After completing a cause-and
      effect analysis, we implemented a solution involving increased outreach to health
      care institutions and saw annual participation increase in 3 out of 4 of our
      programs. We leveraged this work to successfully apply for funding to create a
      centralized referral system, which will facilitate partnerships among local
      health and human service agencies and improve access to services. This is one
      example of how accreditation has benefited our health department and our
      community. We have found that the accreditation process promotes a culture of
      quality and helps health departments identify and address areas for improvement.

PMID- 29595605
TI  - Public Health Employees' Perception of Workplace Environment and Job
      Satisfaction: The Role of Local Health Departments' Engagement in Accreditation.
AB  - OBJECTIVES: To examine the association between local health departments' (LHDs')
      engagement in accreditation and their staffs' perceptions of workplace
      environment and the overall satisfaction with their jobs. DESIGN: Data from the
      2014 Public Health Workforce Interests and Needs Survey (PH WINS) (local data
      only) and the 2014 Forces of Change survey were linked using LHDs' unique ID
      documented by the National Association of County & City Health Officials. The
      Forces of Change survey assessed LHDs' accreditation status. Local health
      departments were classified as "formally engaged" in the Public Health
      Accreditation Board accreditation process if they had achieved accreditation,
      submitted an application, or submitted a statement of intent. The PH WINS survey
      measured employees' perception of 3 aspects of workplace environment, including
      supervisory support, organizational support, and employee engagement. The overall
      satisfaction was measured using the Job in General Scale (abridged). There are
      1884 LHD employees who completed PH WINS and whose agencies responded to the
      question on the accreditation status of the Forces of Change survey. RESULTS:
      When compared with employees from LHDs less engaged in accreditation, employees
      from LHDs that were formally engaged in accreditation gave higher ratings to all
      3 aspects of workplace environment and overall job satisfaction. Controlling for
      employee demographic characteristics and LHD jurisdiction size, the agency's
      formal engagement in accreditation remained related to a higher score in
      perceived workplace environment and job satisfaction. After controlling for
      perceived workplace environment, accreditation status was marginally associated
      with job satisfaction. CONCLUSION: The findings provide support for previous
      reports by LHD leaders on the benefits of accreditation related to employee
      morale and job satisfaction. The results from this study allow us to further
      catalog the benefits of accreditation in workforce development and identify
      factors that may moderate the extent of the benefits. Findings from this study
      show that engagement in public health accreditation is associated with overall
      job satisfaction. This link may be explained by the hypotheses that meeting
      accreditation standards could increase staff satisfaction or that having higher
      job satisfaction could lead to a higher likelihood that a health department would
      apply for accreditation. Further research to explore this relationship is
      critical as many health departments are weighing the value of accreditation as
      they face constrained financial resources.

PMID- 29595606
TI  - From Talk to Action: The Impact of Public Health Department Accreditation on
      Workforce Development.

PMID- 29595607
TI  - Do Accredited State Health Agency Public Health Workforce Development Plans Align
      With the Public Health Workforce Interests and Needs Survey?

PMID- 29595608
TI  - Moving Governance Forward.

PMID- 29595609
TI  - Perspectives on the Impact of Accreditation on the Work of Governing Boards.

PMID- 29595610
TI  - Accreditation's Role in Bolstering Resilience in the Face of the Zika Virus
      Outbreak.
AB  - The Florida Department of Health (Department) received accreditation status as an
      integrated public health system from the Public Health Accreditation Board (PHAB)
      in 2 phases: the State Health Office received accreditation in June 2014 and the
      67 county health departments received accreditation in March 2016. Six weeks
      after PHAB awarded accreditation to the Department as an integrated public health
      system in March 2016, the World Health Organization declared the Zika outbreak in
      the Americas a Public Health Emergency of International Concern. Even in that
      short time, integrated public health accreditation, along with the other
      components of the Department's performance management system, allowed the
      Department to address this public health emergency, especially in Miami-Dade
      County, where the impact of Zika was significant. This case report describes the
      local response in Miami-Dade County and supporting statewide efforts. Public
      health departments should consider how public health accreditation could
      strengthen their ability to fulfill their public health mission. This article
      provides rationale for state and local health departments to seek accreditation.

PMID- 29595611
TI  - Kent County Health Department: Using an Agency Strategic Plan to Drive
      Improvement.
AB  - The Kent County Health Department (KCHD) was accredited by the Public Health
      Accreditation Board (PHAB) in September 2014. Although Michigan has had a state
      level accreditation process for local health departments since the late 1990s,
      the PHAB accreditation process presented a unique opportunity for KCHD to build
      on successes achieved through state accreditation and enhance performance in all
      areas of KCHD programs, services, and operations. PHAB's standards, measures, and
      peer-review process provided a standardized and structured way to identify
      meaningful opportunities for improvement and to plan and implement strategies for
      enhanced performance and established a platform for being recognized nationally
      as a high-performing local health department. The current case report highlights
      the way in which KCHD has developed and implemented its strategic plan to guide
      efforts aimed at addressing gaps identified through the accreditation process and
      to drive overall improvement within our agency.

PMID- 29595612
TI  - State Health Agencies' Perceptions of the Benefits of Accreditation.
AB  - The national voluntary accreditation program serves to encourage health agencies
      to seek departmental accreditation as a mechanism for continuous quality
      improvement. This study utilizes data from the 2016 Association of State and
      Territorial Health Officials Profile Survey to examine the perceived benefits of
      accreditation among state health agencies. Respondents answered questions on
      topics such as agency structure, workforce, and quality improvement activities.
      Frequencies and cross tabulations were conducted using IBM SPSS (version 21)
      statistical software. Results indicate that among accredited agencies, the most
      commonly endorsed benefits of accreditation include stimulating quality and
      performance improvement opportunities (95%), strengthening the culture of quality
      improvement (90%), and stimulating greater collaboration across departments/units
      within the agency (90%). Policy and practice implications, such as how these data
      can be used to promote accreditation within health agencies, as well as how
      accreditation strengthens governmental public health systems, are also discussed.

PMID- 29595613
TI  - Benefits and Perceptions of Public Health Accreditation Among Health Departments
      Not Yet Applying.
AB  - OBJECTIVE: To identify the benefits and perceptions among health departments not
      yet participating in the public health accreditation program implemented by the
      Public Health Accreditation Board (PHAB). DESIGN: Quantitative and qualitative
      data were gathered via Web-based surveys of health departments that had not yet
      applied for PHAB accreditation (nonapplicants) and health departments that had
      been accredited for 1 year. PARTICIPANTS: Respondents from 150 nonapplicant
      health departments and 57 health departments that had been accredited for 1 year.
      RESULTS: The majority of nonapplicant health departments are reportedly
      conducting a community health assessment (CHA), community health improvement plan
      (CHIP), and health department strategic plan-3 documents that are required to be
      in place before applying for PHAB accreditation. To develop these documents, most
      nonapplicants are reportedly referencing PHAB requirements. The most commonly
      reported perceived benefits of accreditation among health departments that
      planned to or were undecided about applying for accreditation were as follows:
      increased awareness of strengths and weaknesses, stimulated quality improvement
      (QI) and performance improvement activities, and increased awareness of/focus on
      QI. Nonapplicants that planned to apply reported a higher level of these
      perceived benefits. Compared with health departments that had been accredited for
      1 year, nonapplicants were more likely to report that their staff had no or
      limited QI knowledge or familiarity. CONCLUSIONS: The PHAB accreditation program
      has influenced the broader public health field-not solely health departments that
      have undergone accreditation. Regardless of their intent to apply for
      accreditation, nonapplicant health departments are reportedly referencing PHAB
      guidelines for developing the CHA, CHIP, and health department strategic plan.
      Health departments may experience benefits associated with accreditation prior to
      their formal involvement in the PHAB accreditation process. The most common
      challenge for health departments applying for accreditation is identifying the
      time and resources to dedicate to the process.

PMID- 29595614
TI  - Driving Change and Reinforcing Expectations by Linking Accreditation With
      Programmatic and Strategic Priorities.

PMID- 29595615
TI  - Accelerating Momentum: The Impact of CDC and RWJF Investments in Support of
      Public Health Accreditation and Quality Improvement.

PMID- 29595616
TI  - Public Health Accreditation Board's Innovation Center Continues the Mission to
      Advance the Quality and Performance of Health Departments.

PMID- 29595617
TI  - Connections in Communities Between Accreditation and Achieving a Culture of
      Health.

PMID- 29595618
TI  - Developing a Culture of Health: Addressing Health Inequities Through a Health
      Department and Community Organizer Partnership.

PMID- 29595619
TI  - Strengthening a Community's Culture of Health Through Public Health
      Accreditation.

PMID- 29595620
TI  - Priority Spokane: A Culture of Health Winner.

PMID- 29595621
TI  - Looking Ahead: Applying Foresight Principles to Public Health Accreditation.

PMID- 29595623
TI  - TO THE EDITOR.

PMID- 29595624
TI  - TO THE EDITOR.

PMID- 29595625
TI  - Psychotropic Drug Intolerance.

PMID- 29595626
TI  - A Case of Congenital Insensitivity to Pain With Anhidrosis Comorbid With
      Attention Deficit Hyperactivity Disorder: Clinical Implications for
      Pathophysiology and Treatment.
AB  - Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal
      recessive genetic disorder caused by a mutation in the neurotrophic tyrosine
      kinase receptor (NTRK1) gene. CIPA is accompanied by abnormal catecholamine
      metabolism and decreased blood concentration of dopamine and norepinephrine.
      Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      of heterogeneous etiology and presentation, and recent reports have suggested a
      pathophysiological role of neurotrophins in ADHD. Furthermore, dopamine and
      norepinephrine are known to play major roles in the pathophysiology of ADHD, and
      the imbalance of monoaminergic and cholinergic systems as an underlying cause of
      ADHD has recently been studied. Here, we report the case of an 11-year-old boy
      with CIPA and comorbid ADHD. Our observations have important clinical
      implications for patients with CIPA. Because of deficiencies in self-control,
      proper management of these patients necessitates a highly structured and
      monitored environment, made dually important by possible comorbidity of ADHD.

PMID- 29595627
TI  - The Potential Efficacy of Psychological First Aid on Self-Reported Anxiety and
      Mood: A Pilot Study: Erratum.

PMID- 29595628
TI  - What is the superior surgical strategy for bi-level cervical spondylosis-anterior
      cervical disc replacement or anterior cervical decompression and fusion?: A meta
      analysis from 11 studies.
AB  - BACKGROUND: Nowadays, anterior cervical artificial disc replacement (ACDR) has
      achieved favorable outcomes in treatment for patients with single-level cervical
      spondylosis. However, It is still controversial that whether or not it will
      become a potent therapeutic alternation in treating 2 contiguous levels cervical
      spondylosis compared with anterior cervical decompression and fusion (ACDF).
      Therefore, we conducted a systematic review and meta-analysis to compare the
      efficacy and safety of ACDR and ACDF in patients with 2 contiguous levels
      cervical spondylosis. METHODS: According to the computer-based online search,
      PubMed, Embase, Web of Science, and Cochrane Library for articles published
      before July 1, 2017 were searched. The following outcome measures were extracted:
      neck disability index (NDI), visual analog scale (VAS) neck, VAS arm, Short Form
      (SF)-12 mental component summary (MCS), SF-12 physical component summary (PCS),
      overall clinical success (OCS), patient satisfaction (PS), device-related adverse
      event (DRAE), subsequent surgical intervention (SSI), neurological deterioration
      (ND), and adjacent segment degeneration (ASD). Methodological quality was
      evaluated independently by 2 reviewers using the Furlan for randomized controlled
      trial (RCT) and MINORS scale for clinical controlled trials (CCT). The chi
      squared test and Higgin I test were used to evaluate the heterogeneity. A P < .10
      for the chi-squared test or I values exceeding 50% indicated substantial
      heterogeneity and a random-effect model was applied; otherwise, a fixed-effect
      model was used. All quantitative data were analyzed by the Review Manager 5.2
      (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).
      RESULTS: Nine RCTs and 2 CCT studies containing 2715 patients were included for
      this meta-analysis. The pooled analysis indicated that the ACDR group is superior
      to ACDF in NDI, VAS neck, PCS score, OCS, PS, DRAE, ASD, and SSI. However, the
      pooled results indicate that there was no significant difference in the ND, VAS
      arm and in MCS score. CONCLUSIONS: The present meta-analysis suggests that for bi
      level cervical spondylosis, ACDR appears to provide superior clinical
      effectiveness and safety effects than ACDF. In the future, more high-quality RCTs
      are warranted to enhance this conclusion.

PMID- 29595629
TI  - Intakes of citrus fruit and risk of esophageal cancer: A meta-analysis.
AB  - Esophageal cancer (EC) is the eighth most common cancer and the sixth most
      frequent cause of cancer death in the whole world. Many studies have investigated
      the association between citrus fruit intake and the risk of EC, but the results
      are inconsistent and not analyzed by category. We aimed to perform a meta
      analysis of studies to evaluate the incidence between citrus fruit consumption
      and subtypes of esophageal cancer and derive a more precise estimation.Through
      searches of PubMed, OVID, and Web of Science we updated 1988 systematic review up
      to April 2016. Based on an inclusion and exclusion criteria, conventional meta
      analysis according to DerSimonian and Laird method was used for the pooling of
      the results. Random-effect models were used to calculate subgroups.Twenty-five
      English articles (20 case-control studies and 5 cohort studies) comprising
      totally 5730 patients of esophageal cancer would be suitable for use in this
      study. The result indicated the inverse associations between intakes of citrus
      fruit and EC (relative risk [RR] = 0.65, 95% confidence interval [CI] 0.56-0.75,
      I  = 51.1%, P = .001), Esophageal squamous cell carcinoma (ESCC) (RR = 0.59, 95%
      CI 0.47-0.76, I  = 60.7%, P = .002), no significant relationship between citrus
      fruit and esophageal adenocarcinoma (EAC) (RR = 0.86, 95% CI 0.74-1.01, I  =
      0.0%, P = .598).This meta-analysis indicates that intakes of citrus fruit
      significantly reduce the risk of ESCC and is no obvious relationship with EAC.
      Further studies about constituents in citrus fruit and its mechanism are
      warranted.

PMID- 29595630
TI  - Clinical and radiographic outcomes of treatment of comminuted Mason type II
      radial head fractures with a new implant.
AB  - This study aims to evaluate the clinical and radiographic treatment outcomes of
      comminuted Mason type II radial head fractures, which underwent open reduction
      and internal fixation (ORIF) using a new implant (mother-child screw, MCS).This
      study included 16 patients (7 male and 9 female patients; mean age: 40.9 years,
      age range: 19-68 years), who were treated with ORIF, followed by MCS fixation for
      comminuted type II radial head fractures. The clinical results were evaluated
      using the Mayo Elbow Performance Score (MEPS). Radiographs, which included the
      quality of fracture reduction, stability, osteoarthritis, and heterotopic
      ossification of the elbow, were investigated. The mean follow-up period was 23.4
      months.Anatomical reduction and bone union were achieved in all patients treated
      with MCS, and mean union time was 6.2 weeks. The average flexion-extension arc of
      elbow motion was 135.6 degrees  (range: 125 degrees -150 degrees ), and the
      average arc of forearm rotation was 155.3 degrees  (range: 145 degrees -170
      degrees ). Furthermore, MEPS was 94.1 (range: 85-100), and the rate of excellent
      and good was 100%. All patients returned to preinjury work within a mean period
      of 11.7 weeks. No heterotopic ossification and joint stiffness of the elbow were
      encountered. Two patients had mild arthritic changes (grade I), but none of these
      patients complained of pain.The use of MCS fixation for comminuted type II radial
      head fractures resulted in good clinical and radiographic outcomes.

PMID- 29595631
TI  - The efficacy of dexamethasone on pain and recovery after total hip arthroplasty:
      A systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Total hip arthroplasty (THA) perioperative dexamethasone treatment is
      still a controversial subject. We write this systematic review and meta-analysis
      to evaluate the efficacy of dexamethasone on pain and recovery after THA.
      METHODS: Two researchers searched the relevant studies from Pubmed, Cochrane, and
      Embase. The research was reported according to the preferred reporting items for
      systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled
      trials (RCTs) were included in our meta-analysis. At the same time, the
      assessment of the risk of bias was conducted according to the Cochrane Handbook
      for Systematic Reviews of Interventions version. The pooled data are processed by
      software RevMan 5.3. RESULT: In accordance with inclusion and exclusion, 3
      studies with 207 patients were eligible and accepted into this meta-analysis. For
      RCTs, the risk of bias was evaluated by Cochrane Collaboration tool. Only one
      study did not have detection bias. Our study demonstrated that the dexamethasone
      group was more effective than the placebo group in term of visual analogue scale
      (VAS) score at 24 hours (P < .001), 48 hours (P = .04); opioid consumption (P <
      .001); length of stay (LOS, P < .001); and postoperative nausea (P = .001).
      CONCLUSION: Dexamethasone not only reduces postoperative pain scores and
      postoperative opioids consumption within 48 hours, but also reduces postoperative
      vomiting and effectively reduces LOS. However, we still need large sample size
      and high quality studies to explore the relationship between complications and
      dose response to give the final conclusion.

PMID- 29595632
TI  - Refractory Mycoplasma pneumoniae pneumonia with concomitant acute cerebral
      infarction in a child: A case report and literature review.
AB  - RATIONALE: Mycoplasma pneumoniae pneumonia, a common cause of community-acquired
      pneumonia in children, is rarely complicated with acute cerebral infarction.
      PATIENT CONCERNS: We present a 7-year-old boy with severe M pneumoniae pneumonia
      who developed impaired consciousness, aphasia, and reduced limb muscle power 7
      days postadmission. DIAGNOSES: Mycoplasma pneumoniae pneumonia with concomitant
      acute cerebral infarction. INTERVENTIONS: The patient recovered with aggressive
      antibiotic therapy, antiinflammation therapy with methylprednisolone, and gamma
      immunoglobulin and anticoagulation therapy with aspirin and low molecular weight
      heparin along with rehabilitation training. OUTCOMES: At 8 days postadmission,
      his consciousness was improved and at the 6-month follow-up visit, his muscle
      power of bilateral upper and lower limbs was normal except still poor right
      handgrip power. LESSONS: Stroke or cerebral infarction should be considered and
      promptly managed in rare cases of M pneumoniae pneumonia with neurologic
      manifestations.

PMID- 29595633
TI  - Vitamin intake and pancreatic cancer risk reduction: A meta-analysis of
      observational studies.
AB  - BACKGROUND: The relationship between vitamin intake and pancreatic cancer (PC)
      risk is disputed. We aimed to investigate the association between vitamin intake
      and the risk of PC via meta-analysis. METHODS: We conducted a meta-analysis of
      studies concerning vitamin intake and the risk of PC from EMBASE, MEDLINE, and
      Cochrane Library. The search yielded 25 correlative studies including 1,214,995
      individuals. The relative risks (RR) were examined by a random-effect model or
      fixed-effect model. Subgroup analysis, dose-response analysis, sensitivity
      analysis, meta-regression, and publication bias analysis were used to analyze
      studies. RESULTS: The RR of PC in the highest vitamin intake group was 0.90 (95%
      confidence interval, 0.83-0.98) compared with that in the lowest vitamin intake
      in the prospective studies. Different increments of vitamin intake and the risk
      of PC were examined with dose-response analysis, and a decrease in the risk of PC
      was observed with vitamin D (25%) and vitamin B12 (27%). CONCLUSIONS: This meta
      analysis found that vitamin intake can decrease the risk of PC, particularly
      vitamin D and vitamin B12.

PMID- 29595634
TI  - Targeted agents for patients with advanced/metastatic pancreatic cancer: A
      protocol for systematic review and network meta-analysis.
AB  - BACKGROUND: Pancreatic cancer (PC) is a devastating malignant tumor. Although
      surgical resection may offer a good prognosis and prolong survival, approximately
      80% patients with PC are always diagnosed as unresectable tumor. National
      Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy
      as efficient treatment. While, according to recent studies, targeted agents might
      be a better available option for advanced or metastatic pancreatic cancer
      patients. The aim of this systematic review and network meta-analysis will be to
      examine the differences of different targeted interventions for
      advanced/metastatic PC patients. METHODS: We will conduct this systematic review
      and network meta-analysis using Bayesian method and according to Preferred
      Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P)
      statement. To identify relevant studies, 6 electronic databases including PubMed,
      EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of
      science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese
      Biological Medical Database) will be searched. The risk of bias in included
      randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook
      version 5.1.0. And we will use GRADE approach to assess the quality of evidence
      from network meta-analysis. Data will be analyzed using R 3.4.1 software. RESULTS
      AND CONCLUSION: To the best of our knowledge, this systematic review and network
      meta-analysis will firstly use both direct and indirect evidence to compare the
      differences of different targeted agents and targeted agents plus chemotherapy
      for advanced/metastatic pancreatic cancer patients. This is a protocol of
      systematic review and meta-analysis, so the ethical approval and patient consent
      are not required. We will disseminate the results of this review by submitting to
      a peer-reviewed journal.

PMID- 29595635
TI  - Aspirin plus dipyridamole has the highest surface under the cumulative ranking
      curves (SUCRA) values in terms of mortality, intracranial hemorrhage, and adverse
      event rate among 7 drug therapies in the treatment of cerebral infarction.
AB  - BACKGROUND: The standardization for the clinical use of drug therapy for cerebral
      infarction (CI) has not yet determined in some aspects. In this paper, we
      discussed the efficacies of different drug therapies (aspirin, aspirin plus
      dipyridamole, aspirin plus clopidogrel, aspirin plus warfarin, cilostazol,
      warfarin, and ticlopidine) for CI. METHODS: We searched databases of PubMed and
      Cochrane Library from the inception to April, 2017, randomized controlled trials
      (RCTs) met the inclusion and exclusion criteria were enrolled in this study. The
      network meta-analysis integrated evidences of direct and indirect comparisons to
      assess odd ratios (OR) and surface under the cumulative ranking curves (SUCRA)
      value. RESULTS: Thirteen eligible RCTs including 7 drug therapies were included
      into this network meta-analysis. The network meta-analysis results showed that CI
      patients who received aspirin plus dipyridamole presented lower mortality when
      compared with those received aspirin plus clopidogrel (OR = 0.46, 95% CI = 0.18
      0.99), indicating aspirin plus dipyridamole therapy had better efficacy for CI.
      As for intracranial hemorrhage (ICH), stroke recurrence, and adverse event (AE)
      rate, there were no significant differences of efficacy among 7 drug therapies.
      Besides, SUCRA values demonstrated that in the 7 drug therapies, aspirin plus
      dipyridamole therapy was more effective than others (mortality: 80.67%; ICH:
      76.6%; AE rate: 90.2%). CONCLUSIONS: Our findings revealed that aspirin plus
      dipyridamole therapy might be the optimum one for patients with CI, which could
      help to improve the survival of CI patients.

PMID- 29595636
TI  - Evidence-based practice guideline of Chinese herbal medicine for primary open
      angle glaucoma (qingfeng -neizhang).
AB  - BACKGROUND: Primary open angle glaucoma (POAG) is a chronic, progressive optic
      neuropathy. The aim was to develop an evidence-based clinical practice guideline
      of Chinese herbal medicine (CHM) for POAG with focus on Chinese medicine pattern
      differentiation and treatment as well as approved herbal proprietary medicine.
      METHODS: The guideline development group involved in various pieces of expertise
      in contents and methods. Authors searched electronic databases include CNKI, VIP,
      Sino-Med, Wanfang data, PubMed, the Cochrane Library, EMBASE, as well as checked
      China State Food and Drug Administration (SFDA) from the inception of these
      databases to June 30, 2015. Systematic reviews and randomized controlled trials
      of Chinese herbal medicine treating adults with POAG were evaluated. Risk of bias
      tool in the Cochrane Handbook and evidence strength developed by the GRADE group
      were applied for the evaluation, and recommendations were based on the findings
      incorporating evidence strength. After several rounds of Expert consensus, the
      final guideline was endorsed by relevant professional committees. RESULTS: CHM
      treatment principle and formulae based on pattern differentiation together with
      approved patent herbal medicines are the main treatments for POAG, and the
      diagnosis and treatment focusing on blood related patterns is the major domain.
      CONCLUSION: CHM therapy alone or combined with other conventional treatment
      reported in clinical studies together with Expert consensus were recommended for
      clinical practice.

PMID- 29595637
TI  - High mobility group box 1 was associated with thrombosis in patients with atrial
      fibrillation.
AB  - INTRODUCTION: High mobility group box 1 (HMGB1) is a member of the HMGB family
      that is involved in inflammatory disease-related thrombosis. We hypothesize that
      HMGB1 and its downstream factors are associated with thrombosis in atrial
      fibrillation (AF). MATERIALS AND METHODS: Our experimental materials were the
      left atrial appendage (LAA) tissues from patients undergoing valve replacement.
      The samples were divided into 3 groups: a sinus rhythm group (n = 15), an
      AF(+)thrombus(-)group (n = 15), and an AF(+) thrombus (+)group (n = 15). The
      expression of HMGB1, Toll-like receptor 4 (TLR4), advanced glycation end product
      (RAGE), myeloid differentiation factor 88 (MyD88), nuclear factor kappaB
      (NFkappaB), p-NFkappaB, and tissue factor (TF) were detected by Western blot and
      immunohistochemical (IHC) staining. The expressions of interleukin-1 beta,
      interleukin 6, and tumor necrosis factor-alpha were detected by quantitative real
      time PCR. RESULTS: The Western blots revealed significantly higher expressions of
      HMGB1, MyD88, p-NFkappaB/NFkappaB, and TF in the AF(+)thrombus(+) group than in
      the other 2 groups. However, no differences in TLR4 or RAGE expression were found
      between the groups. IHC staining also revealed higher expressions of HMGB1 and TF
      in the AF(+)thrombus(+) group. The increased mRNA expressions of classic
      inflammatory factors (i.e., interleukin-1 beta, interleukin 6, and tumor necrosis
      factor-alpha) in AF(+)thrombus(+) group further validated the correlation between
      inflammation and thrombi in atrial fibrillation. CONCLUSIONS: HMGB1 was
      associated with thrombosis in patients with AF via the MyD88/NFkappaB pathway
      after adjustment for cardiac and extra cardiac inflammation variables.

PMID- 29595638
TI  - The role of thromboelastography in predicting hemorrhage risk in patients with
      leukemia.
AB  - This study aimed to compare the efficacy of thromboelastography (TEG) and
      conventional coagulation methods in predicting hemorrhage risk in patients with
      leukemia.A total of 226 patients diagnosed with leukemia were included and
      divided into bleeding and nonbleeding groups. All patients had their blood
      samples taken for TEG test to measure the reaction time (R time), alpha (alpha
      angle), and maximum amplitude (MA) as well as measure platelet count (PLT),
      prothrombin time, and activated partial thromboplastin time. Patients were
      followed up for bleeding episodes.The multivariate analysis showed that PLT [odds
      ratio (OR) = 0.993] and MA (OR = 0.921) have better association with bleeding
      risk. Receiver operating characteristic (ROC) analysis showed that the
      combination of PLT and MA (AUC = 0.824) was better for hemorrhage risk prediction
      than PLT [area under the curve (AUC) = 0.730] and MA (AUC = 0.819) alone.The
      combination of TEG and conventional coagulation methods could help in assessing
      the risk of hemorrhage in patients with leukemia.

PMID- 29595639
TI  - An overlooked cause in a patient with recurrent ischemic stroke: A case report.
AB  - RATIONALE: The majority of ischemic strokes are due to cardioembolism, large
      vessel atherothromboembolism, small vessel occlusive disease, or other unusual
      mechanisms. In most clinical settings, many strokes without a well-defined
      etiology requires a thorough diagnostic evaluation, otherwise the underlying
      cause might be easily overlooked. Here we report on the rare cause of a patient
      with recurrent stroke. PATIENT CONCERNS: A 50-year-old female patient had a 4
      year history of recurrent acute onset of neurological deficits. DIAGNOSES:
      Contrast transcranial Doppler ultrasound detected a typical "curtain" appearance
      of microbubbles, indicative of a right-to-left shunt. Computed tomography
      pulmonary angiogram was then initiated and a pulmonary arteriovenous malformation
      (PAVM) in the left lower lobe was found. INTERVENTIONS: The patient underwent
      percutaneous closure of PAVM. Afterward, warfarin was commenced because of the
      high risk of further thromboembolic complications in the following weeks to
      months. Post-treatment computed tomography pulmonary angiogram (CTPA)
      demonstrated successful closure of PAVM. No microbubble signals were detected on
      post-treatment contrast transcranial Doppler ultrasound (TCD) study. OUTCOMES:
      The patient suffered no further embolic events during 3-year follow-up. No
      recanalization or new PAVMs were detected on CT scan. LESSONS: Neurological PAVM
      associated risks are common but remain poorly recognized. A strategic protocol is
      imperative in searching for the etiologies of cryptogenic stroke.

PMID- 29595640
TI  - Comparison of the effects of oxycodone versus fentanyl on airway reflex to
      tracheal extubation and postoperative pain during anesthesia recovery after
      laparoscopic cholecystectomy: A double-blind, randomized clinical consort study.
AB  - BACKGROUND: Fentanyl has been suggested to be effective for controlling airway
      and hemodynamic responses to tracheal extubation. This study was performed to
      compare the effects of oxycodone and fentanyl on airway and hemodynamic responses
      and postoperative pain during the recovery period in patients undergoing
      laparoscopic cholecystectomy. METHODS: Ninety patients aged 18 to 65 years were
      randomly allocated to 1 of 3 groups: fentanyl, oxycodone, and control. Coughing
      responses (incidence and severity), hemodynamic responses during the recovery
      period, and acute postoperative pain were assessed. RESULTS: The incidence of
      cough was decreased in the fentanyl and oxycodone groups compared with that in
      the control group at the points of awareness and extubation, and no significant
      difference was observed between the 2 treatment groups. Severe cough response was
      decreased in the fentanyl and oxycodone groups compared with that in the control
      group at the point of extubation, and no significant change was observed in cough
      severity between the 2 treatment groups. Postoperative pain scores were lower in
      the fentanyl and oxycodone groups than those in the control group at 5 and 30
      minutes postoperatively, and no significant difference was observed between the 2
      treatment groups. Hemodynamic responses did not differ among the 3 groups during
      the recovery period. CONCLUSION: Oxycodone treatment before tracheal extubation
      reduced cough response and was as effective as fentanyl treatment for improving
      extubation quality. Furthermore, single boluses of fentanyl and oxycodone showed
      equal effectiveness in attenuating acute postoperative pain in patients
      undergoing laparoscopic cholecystectomy.

PMID- 29595641
TI  - Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms.
AB  - The gene - environment (G * E) interaction effect is involved in severe mental
      disorders. However, whether the brain-derived neurotrophic factor (BDNF) Val66Met
      polymorphism participates in the childhood-abuse influenced schizophrenic
      symptoms remains unclear. We examined the interaction between BDNF Val66Met, and
      childhood trauma (ChT) on psychotic symptoms in a Chinese Han population.To
      estimate the G * E interaction, psychiatric interviews, self-report
      questionnaires for ChT, and genotyping for BDNF Val66Met were carried out on 201
      schizophrenic patients. G * E interactions were analyzed by generalized
      multifactor dimensionality reduction (GMDR).Among all patients, 11.9%, 19.4%,
      23.4%, 26.4%, and 73.6% reported emotional abuses, physical abuses (PA), sexual
      abuses (SA), emotional neglects (EN), and physical neglects (PN), respectively.
      Significant negative correlations were observed between anxiety/depression
      factors, and ChT total scores. Patients with 3 different BDNF genotypes showed
      significant differences in anxiety/depression scores. Significant 2-way
      interactions were found for Val66Met * PN, 3-way interactions were found for
      Val66Met * PN * PA, and four-way interactions were found for Val66Met * PN * PA *
      EN with regard to the excitement scores.Our findings suggested an involvement of
      BDNF Val66Met polymorphism after ChT in terms of risk for schizophrenia symptoms.

PMID- 29595642
TI  - Efficacy of febuxostat in hyperuricemic patients with mild-to-moderate chronic
      kidney disease: a meta-analysis of randomized clinical trials: A PRISMA-compliant
      article.
AB  - BACKGROUND: To investigate the efficacy of febuxostat in hyperuricemic patients
      with chronic kidney disease (CKD), relevant randomized clinical trials (RCTs)
      were analyzed. METHODS: We used PubMed, Medline, ISI Web of Science, CBMdisc, and
      Cochrane Library databases to conduct a systematic literature research. A fixed
      effects model was used to evaluate the standardized mean differences (SMDs) with
      95% confidence intervals (CIs). We conducted subgroup analysis, sensitivity
      analysis, and analyzed publication bias, to comprehensively estimate the
      renoprotective effects of febuxostat in hyperuricemic patients with CKD. RESULTS:
      Among 296 retrieved studies, 5 relevant RCTs were included in the meta-analysis.
      The result showed that serum estimated glomerular filtration rate (eGFR) was
      improved after febuxostat treatment in hyperuricemic patients with CKD, with an
      SMD (95% CI) of 0.24 [-0.17 to 0.43] and P = .67 (fixed-effects model). No
      heterogeneity was observed across studies (I  = 0% and P = .67). Subgroup
      analysis suggested that treatment-related reductions in serum eGFR levels were
      not related to drug doses, intervention times, or region. CONCLUSIONS: The
      present meta-analysis suggests that febuxostat may slow the progression of mild
      to-moderate CKD. Given the limited number of included studies, additional large
      sample-size RCTs are required to determine the long-term renoprotective effects
      of febuxostat in hyperuricemic patients with CKD.

PMID- 29595643
TI  - Effects of Kimchi on human health: A protocol of systematic review of controlled
      clinical trials.
AB  - BACKGROUND: Kimchi, a traditional, fermented Korean food that is consumed daily,
      has been recognized as a health food due to its beneficial effects on human
      health. The aim of this overview is to critically evaluate all clinical trials of
      the use of Kimchi in the treatment of any condition or symptom. METHODS AND
      ANALYSIS: Eight databases will be searched from inception until March 2018. We
      will include all prospective trials, including randomized controlled trials
      (RCTs), non-RCTs, and uncontrolled trials. The methodological quality of the
      trials will be assessed using Cochrane risk of bias (ROB) assessment tool and ROB
      in nonrandomized studies-I for RCTs and non-RCTs, respectively. ETHICS AND
      DISSEMINATION: Ethical approval will not be required, given that this protocol is
      for a systematic review. The full systematic review will be published in a peer
      reviewed journal. The review will also be disseminated electronically and in
      print. Updates of the review will be conducted to inform and guide health care
      practice and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2018 CRD42018087375.

PMID- 29595644
TI  - Herbal medicine for Behcet's disease: A protocol for a systematic review and meta
      analysis.
AB  - BACKGROUND: Herbal medicine treatment is often recommended in order to raise
      immunity levels and reduce the possibility of recurrence of symptoms, and
      treating the fundamental causes of the disease. This systematic review will
      assess the efficacy of herbal medicine in treating Behcet's disease. METHODS AND
      ANALYSIS: We will search the following 11 electronic databases from their
      inception: PubMed, EMBASE, and CENTRAL; 3 Chinese databases (CNKI, Wanfang, and
      VIP); and 5 Korean databases (OASIS, DBpia, RISS, KISS, and KoreaMed). The data
      will be extracted independently by 2 authors using predefined criteria.
      Disagreements will be resolved by discussion between the authors. The risk of
      bias will be assessed using the Cochrane tool for assessing risk of bias. ETHICS
      AND DISSEMINATION: Ethical approval will not be required, given that this
      protocol is for a systematic review. The review will be published in a journal.
      Updates of the review will be conducted periodically to inform and guide
      healthcare practice and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2018
      CRD42018085493.

PMID- 29595645
TI  - Effectiveness of liposome bupivacaine for postoperative pain control in total
      knee arthroplasty: A PRISMA-compliant meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Adequate pain control after total knee arthroplasty (TKA) enables
      quicker recovery and reduces readmissions and treatment costs. The aim of this
      study was to determine the effect of liposomal bupivacaine (LB) for postoperative
      pain control in patients prepared for TKA. METHODS: We searched for the reports
      that evaluating the effect of liposomal bupivacaine for postoperative pain
      control in patients prepared for TKA between March 1983 and May 2017 in the
      electronic database Cochrane Central Register of Controlled Trials (CENTRAL),
      PubMed, EMBASE, Web of Science, and Ovid. The main outcomes were visual analog
      scale (VAS) at 24, 48, and 72 hours. The secondary outcomes were total morphine
      consumption, the length of hospital stay, range of motion, and the occurrence of
      nausea. RESULTS: Seven randomized controlled trials (RCTs) enrolling 825
      patients, with 413 in the LB group and 412 in the control group, were included in
      this meta-analysis. Our results suggested that administration LB was associated
      with a reduction of VAS by 4.22 points at 72 hours after TKA (WMD = -4.22, 95% CI
      -7.47, -0.97, P = .011) on a 100-point VAS. What's more, LB can decrease the
      occurrence of nausea when compared with traditional bupivacaine by 18.3% (risk
      ratio  = 0.70, 95% confidence interval 0.55, 0.89, P = .003). LB was associated
      with an increase of the range of motion than traditional bupivacaine (P < .05).
      There was no significant difference between the VAS at 24, 48 hours, total
      morphine consumption and the length of hospital stay. CONCLUSIONS: Administration
      with LB was associated with pain-relieving effects and reduces the morphine
      related complications (nausea). Due the limited number of the included RCTs,
      large number and high quality RCTs are still need to identify the effects of LB
      for pain control after TKA.

PMID- 29595646
TI  - Urological complications after radical hysterectomy with postoperative
      radiotherapy and radiotherapy alone for cervical cancer.
AB  - Radiotherapy is a reliable method to cure cervical cancer patients, but it could
      cause serious urological complications after the treatment due to the anatomical
      location of the cervix. The main purpose of this retrospective analysis is to
      study the incidence, latency, and therapeutic efficacy of urological
      complications caused by radical hysterectomy with postoperative radiotherapy or
      radiotherapy alone in patients with cervical cancer.A retrospective analysis was
      conducted on patients with cervical cancer who received radical hysterectomy with
      postoperative radiotherapy or radiotherapy alone at the First Hospital of Jilin
      University between January 2010 and May 2016. The urological complications were
      confirmed by clinical manifestation, ultrasound, computed tomography (CT),
      nuclear scintigraphy, and assessment of renal function. All the patients with
      urological complications received conventional treatment, including conservative,
      electrosurgery, ureteral stents, nephrectomy, and neoplasty. The onset time of
      radiation injury symptoms was confirmed according to the medical history and
      follow-up. The surveillance for the therapeutic effects for these complications
      was accomplished by cystoscopy, imaging, and laboratory assessment.The overall
      rate of urological complications after treatment was 3.26%, comprising 2.12%
      ureteral obstruction, 0.98% radiocystitis, and 0.16% vesicovaginal fistula. The
      incidence of ureteral obstruction in patients treated with radical hysterectomy
      with postoperative radiotherapy and radiotherapy alone was not statistically
      significant (2.18% vs 1.59%, P > .05). The median onset time of radiocystitis and
      ureteral obstruction was 10 months (0-75 months) and 12 months (2-66.3 months),
      respectively. The onset time of vesicovaginal fistula was 3.5 months. After the
      appropriate treatment, the majority of the complications were under control.The
      incidence of urological complications is acceptable. There was no statistical
      difference in the risk between patients treated with radical hysterectomy with
      postoperative radiotherapy and radiotherapy alone. The latency period between
      radiotherapy and the manifestation of urological complications may be relatively
      long. So it is crucial to underline long-term follow-up after radiotherapy. The
      majority of urological complications were alleviated after symptomatic treatment
      and the patients with cervical cancer achieved long-term remissions or cures.

PMID- 29595647
TI  - Ultrasound-guided minimally invasive percutaneous nephrolithotomy in the
      treatment of pediatric patients <6 years: A single-center 10 years' experience.
AB  - Owing to the fragile kidney and relative small collecting system of pediatric
      patients, urologists were always reluctant to treat pediatric urolithiasis with
      PCNL. Here we conduct a study to assess the effectiveness and safety of pediatric
      patients with renal calculi <6 years.A total of 88 pediatric patients (99 kidney
      units) <6 years underwent the ultrasound (US)-guided minimally invasive
      percutaneous nephrolithotomy in our institute from March 2006 to April 2016. The
      mean age was 30.9 months (range, 7-72 months). The mean stone size was 19.5 mm
      (range, 10-50 mm). The group included single stone in 35 kidney units, upper
      ureteral stone in 12 kidney units, multiple stone in 43 kidney units, and
      staghorn stone in 9 kidney units. The procedure of puncture and dilation were
      guided by US solely.The mean operation time was 52.3 minutes (range, 15-140
      minutes). The mean postoperative length of stay was 6.0 days (3-16 days).
      Besides, the initial stone free rate (SFR) was 90.9% (90/99) and the final SFR
      was 96.0% (95/99). The mean hemoglobin drop was 10.9 g/L (range, 1-25 g/L).
      Postoperative complications occurred in 12 patients including fever in 11 cases
      and active pleural effusion in 1 case.The US-guided MPCNL is an effective and
      safety procedure to treat pediatric patients with stone <6 years.

PMID- 29595648
TI  - Clinical application of the sinus tarsi approach in the treatment of intra
      articular calcaneal fracture.
AB  - To observe the clinical outcome of the sinus tarsi approach in the operative
      treatment of intra-articular calcaneal fractures.Forty-nine intra-articular
      calcaneal fractures in 45 patients were managed surgically with sinus tarsi
      approach. The anatomical plate and compression bolts were applied in 14 feet. The
      anatomical plate and screws were applied in 35 feet. Maryland foot score system
      was used to evaluate the function of the hindfoot at the followup.The reduction
      of the posterior facet was graded as nearly anatomical (less than 2 mm articular
      displacement) in 46 feet (93.9%). The width, height, and Bohler angle were
      significantly improved in all patients (P < .01). After a mean follow-up period
      of 18.7 months (14.5-29 months), the Maryland foot scores were: 34 feet scored 90
      100 points (excellent), 6 feet scored 80-90 points (good), 6 feet scored 70-80
      points (fair), and 3 feet scored 60-70 points (poor). Incision-edge necrosis
      occurred in 2 cases. One case suffered from incomplete medial plantar nerve
      injury. One case suffered from heel pad branch of the tibial nerve injury. Six
      cases suffered from sural nerve injury, and 4 cases sustained a lateral wound
      dehiscence due to a hematoma. No case suffered from lateral impingement syndrome.
      Up to now, no patient had to accept subtalar arthrodesis.Sinus tarsi approach
      provides good exposure to the subtalar joint. Open reduction and internal
      fixation of calcaneus fractures through a sinus tarsi approach allows adequate
      reduction with low risk of wound-healing complications.

PMID- 29595649
TI  - Next-generation sequencing provides an added value in determining drug resistance
      and viral tropism in Cameroonian HIV-1 vertically infected children.
AB  - With limited and low-genetic barrier drugs used for the prevention of mother-to
      child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted
      HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric
      strategies.The aim of this study was to ascertain HIVDR and viral-tropism in
      majority and minority populations among Cameroonian vertically infected
      children.A comparative analysis among 18 HIV-infected children (7 from PMTCT
      exposed mothers and 11 from mothers without PMTCT-exposure) was performed. HIVDR
      and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained by both
      Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1%
      threshold.Overall, median (interquartile range) age, viremia, and CD4 count were
      6 (4-10) years, 5.5 (4.9-6.0) log10 copies/mL, and 526 (282-645) cells/mm,
      respectively. All children had wild-type viruses through both Sanger sequencing
      and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%),
      born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15
      (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic
      viruses was 0% (0/6) below 5 years (also as minority species), and became
      relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were
      higher with CD4 <=15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580);
      similarly for CD4 <=200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm, P =
      .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority
      species in all but 1 children, thus supporting the safe use of these drug-classes
      in those without such mutations, henceforth sparing ritonavir-boosted protease
      inhibitors or integrase inhibitors for the few remaining cases. In children under
      five years, X4-tropic variants would be rare, suggesting vertical-transmission
      with CCR5-tropic viruses and possible maraviroc usage at younger ages.

PMID- 29595650
TI  - Accuracy and safety of ultrasound-guided percutaneous needle core biopsy of renal
      masses: A single center experience in China.
AB  - Our aim is to determine the sufficiency, accuracy, and safety of ultrasound
      guided percutaneous needle core biopsy of renal masses in Chinese
      patients.Patients who had undergone ultrasound-guided needle core renal mass
      biopsy from June 2012 to June 2016 at West China Hospital, China were
      retrospectively reviewed. The information obtained included demographics, mass
      related parameters, biopsy indications, technique, complications, pathologic
      results, and follow-up. Concordance of surgical resection pathology and follow-up
      data were assessed.Renal mass biopsies were performed in 106 patients. Thirty
      nine (36.8%) were asymptomatic. The male/female ratio was 60/46, with a median
      age of 49.5 years. Median mass size was 8.1 cm (range 1.8-20). Biopsy was
      performed through a 16-gauge needle, with median cores of 2 taken (range 1-5).
      Only one significant biopsy-related complication (hemorrhage requiring
      transfusion) was encountered. An adequate tissue sample was obtained in 97.2%
      (103/106) of biopsies. Eighty-seven biopsies (82.1%) showed malignant neoplasms,
      16 (15.1%) yielded benignity, and 3 (2.8%) were nondiagnostic. After biopsy, 46
      patients (43.4%) underwent surgery. Compared with the subsequent mass resection
      pathology, the biopsy diagnoses were identical in 43 cases. The accuracy rate of
      biopsy distinguishing malignant from benign lesions was 99.1%, and the rate for
      determining tumor histological type (excluding the nondiagnostic biopsies) was
      95.1%. The sensitivity and specificity in detecting malignancy were 98.9% and
      100%, respectively.In several situations, there is still a role for biopsy before
      intervention. Percutaneous needle core biopsy under ultrasonography guidance is
      highly accurate and safe, and can determine the proper management of undefinable
      masses.

PMID- 29595651
TI  - Bronchoscopic valve placement for the treatment of persistent air leaks.
AB  - Persistent air leaks (PALs) are associated with increased morbidity, prolonged
      hospital stay, and increased treatment costs. Endobronchial 1-way valves have
      been recently used as a potential less invasive treatment option. We sought to
      investigate the effects of valve therapy in treating this condition. The patients
      with evidence of continuous air leak flow whose chest tubes remained in place for
      more than 7 days were treated with bronchoscopic closure using 1-way valves. The
      source of the air leak was identified by the Chartis system.A total of 11
      patients (1 woman, 10 men; mean age, 68 years) who underwent valve placement were
      eligible to be enrolled from January 2015 through January 2017. Six patients had
      postoperative PAL, and 5 had a secondary spontaneous pneumothorax. The number of
      used valves varied from 1 to 3 (median 1). The resolution of the leak was
      complete in 8 patients (72.7%), whose mean duration of air leak before and after
      valve deployment was 58.5 and 4.5 days, respectively. There were no complications
      related to the valve deployment.Bronchoscopic placement of 1-way valves is a safe
      procedure that could help manage patients with prolonged PALs. A prospective
      randomized trial with cost-efficiency analysis is necessary to better define the
      role of this bronchoscopic intervention and demonstrate its effect on air leak
      duration.

PMID- 29595652
TI  - Determinants of lymph node count and positivity in patients undergoing surgery
      for colon cancer.
AB  - Prognosis in colon cancer is based on pathological criteria including TNM
      staging. However, there are deficiencies in this approach, and the lymph node
      ratio (LNR) has been proposed to improve the prediction of outcomes. LNR is
      dependent on optimal retrieval of lymph nodes-lymph node count (LNC). Recent
      studies have suggested that an elevated preoperative systemic inflammatory
      response (SIR) was associated with a lower LNC and a higher LNR. However, there
      are a number of potential confounding factors. The aim of the present study was
      to examine, in detail, these relationships in a large cohort of patients.A
      prospectively maintained database of all patients undergoing colon cancer
      resection in our institution was examined. The SIR was measured by a number of
      inflammatory markers and their scores: modified Glasgow Prognostic Score (mGPS)
      (C-reactive protein/albumin), neutrophil lymphocyte ratio (NLR), platelet
      lymphocyte ratio (PLR), and lymphocyte monocyte ratio (LMR) using standard
      thresholds. The relationships between LNC and LNR, and clinicopathological
      characteristics (including the mGPS, NLR, PLR, and LMR) were examined using chi
      square test for trend and binary logistic regression analysis, where
      appropriate.Of the 896 patients included in the study, 418 (47%) were male, the
      median LNC was 17 (1-71), and the median LNR in node positive disease was 0.16
      (0.03-1). On multivariate analysis, there was a significant independent
      relationship between an elevated LNC (>=12) and laparoscopic surgery (P < .001),
      right-sided tumors (P < .001), later date of resection (2007-2016) (P < .001), T
      stage (P < .001), and venous invasion (P < .001). In those patients with a LNC
      >=12 and node-positive disease (n = 272), on multivariate analysis, there was a
      significant relationship between an elevated LNR (>=0.25), and T stage (P < .01)
      and differentiation (P < .05). Finally, in patients with node-positive disease
      who had surgery later (2007-2016), LNR was directly superior to N stage for both
      cancer-specific survival (LNR: hazard ratio [HR] 2.62, 95% confidence interval
      [CI] 1.25-5.52, P = .011) and overall survival (LNR: HR 2.02, 95% CI 1.12-3.68, P
      = .022).Neither LNC nor LNR was associated with markers of the SIR; however, LNC
      and LNR were directly associated. In high-quality surgical and pathological
      practice, LNR had superior prognostic value compared with N stage in patients
      undergoing surgery for colon cancer.

PMID- 29595653
TI  - Type I Gaucher disease with bullous pemphigoid and Parkinson disease: A case
      report.
AB  - RATIONALE: Gaucher disease (GD) is a rare genetic lysosomal storage disorder
      inherited in an autosomal recessive pattern. GD is due to the deficiency of a
      lysosomal enzyme, acid beta-glucosidase (or glucocerebrosidase). Type 1 Gaucher
      disease (GD1) is characterized by thrombocytopenia, anemia, an enlarged spleen,
      and liver as well as bone complications (Erlenmeyer flask deformity,
      osteoporosis, lytic lesions, pathological and vertebral fractures, bone infarcts,
      and avascular necrosis leading to degenerative arthropathy). The diagnosis is
      usually made in first decades but is sometimes delayed. Parkinson disease,
      neoplasia, and immune system abnormalities may be associated with GD1. PATIENT
      CONCERNS: A patient known for hepatosplenomegaly with hyperferritinemia, anemia,
      and thrombocytopenia was admitted for Lewy body dementia and bullous pemphigoid.
      DIAGNOSES: Type 1 Gaucher disease. INTERVENTION: No specific treatment started.
      OUTCOMES: patient died ten months later due to pneumonia. LESSONS: To the best of
      our knowledge, this is the first case of the association between GD1, bullous
      pemphigoid, and Lewy body dementia. We discuss the central role of alpha
      synuclein in these pathologies.

PMID- 29595654
TI  - Traumatic C1-2 rotatory subluxation with dens and bilateral articular facet
      fractures of C2: A case report.
AB  - RATIONALE: To the best of our knowledge, this is an extremely rare case of
      traumatic C1-2 rotatory subluxation associated with multiple C2 fractures.
      PATIENT CONCERNS: We report the case of a 63-year-old man with type 2 traumatic
      C1-2 rotatory subluxation (Fielding and Hawkins classification) associated with
      type III dens (Anderson and D'Alonzo classification) and bilateral articular
      facet fractures of C2. This injury occurred as a result of falling down in a
      drunken state. The patient complained of neck pain and mild degree of torticollis
      but did not show any neurologic abnormalities. DIAGNOSES: Plain radiographs of
      cervical spine showed extensive soft tissue swelling, a fracture fragment,
      disruption of spinolaminar line at C1-2 level, and bony overlapping of right side
      lateral joint of C1-2. Two- and three-dimensional reconstructed computed
      tomography scans clearly demonstrated complicated C1-2 combined injury. The
      atlantodental interval was normal. INTERVENTION: By skull traction and
      derotation, closed reduction of C1-2 rotatory subluxation with a type III dens
      and bilateral articular facet fractures of C2 was successfully achieved. He was
      managed with halovest fixation for 3 months. OUTCOMES: At the 1-year follow-up
      visit solid fusion and improvement of clinical symptoms were achieved without C1
      2 instability. LESSONS: Despite traumatic C1-2 rotatory subluxation associated
      with multiple C2 fractures, trial of closed reduction should be considered as the
      first choice of treatment so as to preserve C1-2 motion.

PMID- 29595655
TI  - The prognostic value of circulating cell-free DNA in breast cancer: A meta
      analysis.
AB  - BACKGROUND: Circulating cell-free DNA (cfDNA) isolated from plasma or serum by
      noninvasive procedures can serve as a "liquid biopsy" and has potential as a
      biomarker for the tumor burden and survival prediction of breast cancer (BC).
      However, its prognostic value in patients with BC is currently under debate. The
      aim of this meta-analysis was to investigate the relationship between cfDNA and
      survival outcome. METHODS: We systematically searched PubMed, Embase, and Science
      Citation Index electronic databases for studies about the prognostic utility of
      cfDNA in patients with BC. The clinical characteristics, relapse/disease-free
      survival (RFS/DFS), and overall survival (OS) data were extracted from the
      eligible studies. The hazard ratios (HR) and 95% confidence intervals (CI) were
      calculated and pooled with a fixed-effects model using the Stata12.0 software.
      Subgroup and sensitivity analyses were also performed. RESULTS: This meta
      analysis included a total of 10 eligible studies and 1127 patients with BC. The
      pooled HR with 95% CI showed strong associations between cfDNA and OS (HR = 2.41,
      95% CI, 1.83-3.16) along with DFS/RFS (HR = 2.73, 95% CI, 2.04-3.67) in patients
      with BC. Although publication bias was found in the studies regarding RFS/DFS,
      further trim and fill analysis revealed that the adjusted HR would be 2.53 (95%
      CI, 1.83-3.51), which is close to the original HR. Subgroup analyses confirmed
      the role of cfDNA as a strong prognostic marker in patients with BC, regardless
      of cfDNA analysis, sampling time, sample source, detection method, tumor stage,
      sample size, or area. CONCLUSIONS: Our meta-analysis indicates that cfDNA is a
      strong predictive and prognostic marker in patients with BC.

PMID- 29595656
TI  - The association between myocardial infarction and intravitreal bevacizumab
      injection.
AB  - To evaluate the risk of myocardial infarction (MI) after receiving intravitreal
      bevacizumab (IVB) injection. We retrospectively reviewed the charts of patients
      who had received IVB injection in 2016, and grouped them according to whether
      they received the injection for age-related macular degeneration (AMD), diabetes
      related complications, or retinal vein occlusion (RVO). We then investigated the
      prevalence of MI within 2 months after IVB injection and analyzed the possible
      association of IVB with MI. During 2016, 724 patients were enrolled and received
      a total of 1870 IVB injections. Seven patients were diagnosed with MI within 2
      months after receiving an IVB injection. Of 274 patients with AMD, 2 were
      diagnosed with MI; of 311 patients with diabetes-related complications, 3 were
      diagnosed with MI; and of 139 patients with RVO, 2 were diagnosed with MI (P =
      0.785). All MIs occurred between 3 days and 3 weeks after IVB injection (mean =
      14.00 +/- 6.45 days). The MIs after receiving IVB were associated with previous
      history of MI or cerebrovascular infarction in multivariate logistic regression
      analysis (P = 0.005). There was no significant difference in MI prevalence after
      IVB injection according to the reason for receiving the injection. However, care
      should be taken when administering IVB injections, especially to patients with
      risk factors such as history of MI or cerebrovascular infarction.

PMID- 29595657
TI  - Analysis of epidural waveform for cervical epidural steroid injections confirmed
      with fluoroscopy.
AB  - The identification of epidural space with loss of resistance (LOR) is commonly
      performed. But it lacks specificity. Epidural pressure waveform analysis (EPWA)
      provides a simple confirmative adjunct for LOR. If the needle is located within
      the epidural space, measurement of the pressure at its tips shows a pulsatile
      waveform. Previous studies demonstrated satisfactory sensitivity and specificity
      of EPWA. However, success or failure of epidural injection was confirmed by the
      pinprick test, which is limited for patients in the setting of the pain clinic.
      In this study, we evaluated the sensitivity, specificity, as well as positive and
      negative predictive values of EPWA for cervical epidural steroid injection (CESI)
      confirmed by fluoroscopy.One hundred and five CESIs of 75 patients suffering from
      neck and radicular arm pain of over 3 months duration were enrolled. The
      physician injected 5 mL of normal saline after a feeling of satisfactory LOR.
      Saline filled extension tubing, connected to a pressure transducer, was attached
      to the needle. A 3 mL bolus of contrast medium was injected to confirm the
      success of CESI.The incorrect identification of epidural space with LOR (false
      LOR) was 29.5%. Of these 31 failed CESIs, 2 showed epidural waveform and 29 did
      not. The sensitivity, specificity, positive and negative predictive value of EPWA
      was 94.5%, 93.5%, 97.2%, and 87.7%, respectively.EPWA shows satisfactory
      reliability and is a simple adjunct to decrease false LOR for CESI. Further
      confirmative studies are required before its routine use in clinical practice.

PMID- 29595658
TI  - High scavenger receptor class B type I expression is related to tumor
      aggressiveness and poor prognosis in lung adenocarcinoma: A STROBE compliant
      article.
AB  - Scavenger receptor class B type I (SR-B1) is highly expressed in a variety of
      cancers, including prostate, breast and ovarian. However, the relationship
      between SR-B1 and lung adenocarcinoma is unknown. We analyzed the expression of
      SR-B1 in a well-characterized lung adenocarcinoma tissue microarray by
      immunohistochemistry, in 90 cancerous and 90 adjacent normal lung tissues.
      Results showed that the positive expression rate of SR-B1 in cancer tissues
      (86/90, 96%) was significantly higher than that of adjacent tissues (50/90, 56%)
      (P < .001). And SR-B1 overexpression in lung adenocarcinoma tissue was
      significantly higher than that of adjacent normal tissue (P < .001), accounting
      for 67% of cases. This elevated SR-B1 expression was associated with AJCC stage
      (P < .001), T stage (P = .012), N stage (P = .002), and lymph node positivity (P
      < .001). The Kaplan-Meier survival analysis indicated that patients with high SR
      B1 expression had a shorter overall survival (P < .001). On the multivariate
      analysis, SR-B1 was an independent prognostic factor for outcomes after
      adjustment for other prognostic factors (P = .038). In conclusion, high SR-B1
      expression is associated with conventional pathologic parameters that represent
      tumor aggressiveness and may purport a poor clinical prognosis in lung
      adenocarcinoma.

PMID- 29595659
TI  - Change in radial artery pulse wave in stroke hemiplegic patients: Protocol for a
      case-control study.
AB  - INTRODUCTION: About 55% to 75% of stroke survivors have motor disorders and
      problems that affect their quality of life. The prevention of secondary
      neurological damages through relapse prevention and the rehabilitation of stroke
      patients suffering from morbidities are crucial to improve the prognosis of
      patients with stroke. Pulse examinations can be used to determine the stroke
      progression. This study will investigate the differences and changes in radial
      artery pressure-pulse waves during the treatment of hemiplegia caused by stroke.
      METHODS/DESIGN: This study protocol is for a prospective matched case-control
      study. A total of 84 participants will be recruited, 56 patients with hemiplia
      caused by stroke, and 28 control patients matched by age, gender, and body mass
      index. The primary outcome of this study will be the differences and changes in
      the radial augmentation index. DISCUSSION: The results of the study will help to
      determine the differences and changes in radial artery pressure-pulse waves
      during the treatment of hemiplegia caused by stroke. The findings will provide
      information about the physiological and hemodynamic mechanisms. CONCLUSION: This
      will be the first study to analyze the pulse wave of the radial artery (PWRA) on
      the affected side and on the normal side in stroke patients with hemiplegia. This
      study will clarify whether the radial artery pressure pulse wave can be used to
      evaluate the result of stroke treatment objectively. The results of the study
      will be available in February 2019. The version of the protocol is v1.6 written
      in March 7, 2016. ETHICS AND DISSEMINATION: Written informed consent will be
      obtained from all participants. This study has been approved by the Institutional
      Review Board (IRB) of Wonkwang University Gwangju Hospital, Gwangju, Republic of
      Korea (WKIRB-2016/8). The study findings will be published in peer-reviewed
      journals and presented at national and international conferences. TRIAL
      REGISTRATION NUMBER: This trial was registered with the Clinical Research
      Information Service (CRIS) of the Korea National Institute of Health (NIH),
      Republic of Korea (KCT0002147).

PMID- 29595660
TI  - Sealing of the cystic and appendix arteries with monopolar electrocautery during
      laparoscopic combined cholecystectomy and appendectomy.
AB  - The best method to ligate the arteries during laparoscopic cholecystectomy or
      appendectomy remains controversy. The aim of this study is to introduce a new
      approach during laparoscopic combined cholecystectomy and appendectomy using a
      monopolar electrocautery to seal the cystic and appendix arteries. We
      retrospectively reviewed data from 57 patients who underwent laparoscopic
      combined cholecystectomy and appendectomy between December 2006 and June 2016.
      Each laparoscopic combined cholecystectomy and appendectomy was performed by
      coagulating and sealing the cystic and appendix arteries. Absorbable clip or
      coils were then used to ligate the proximal of cystic duct and the stump of
      appendix. The other side of the cystic duct and appendix which subsequently were
      to be removed from abdomen were used titanium clips or silk ligature. Of the 57
      patients, 3 patients (5.3%) were converted to open surgery due to severe
      abdominal adhesions or gallbladder perforation. The mean operative time was 56
      minutes (range, 40-80 minutes). Mean blood loss was 12 mL (range, 5-120 mL), and
      the mean postoperative hospital stay was 3.0 days (range, 2-5 days). No
      postoperative bleeding, biliary leakage, infection, or mortality occurred.
      Monopolar electrocautery to seal the cystic and appendix arteries is a safe,
      effective, and economical surgical procedure during laparoscopic combined
      cholecystectomy and appendectomy. Further randomized controlled clinical trials
      are required to validate our findings.

PMID- 29595661
TI  - Fine needle biopsy is superior to fine needle aspiration in endoscopic ultrasound
      guided sampling of pancreatic masses: A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The comparison between endoscopic ultrasound (EUS) guided fine needle
      aspiration (FNA) and EUS guided fine needle biopsy (FNB) in sampling pancreatic
      masses is still controversial. METHODS: A systematic search was conducted in
      PubMed and Web of Science to identify all relevant randomized controlled trials
      (RCTs). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated
      for dichotomous outcomes of interest (specimen adequacy, diagnostic accuracy,
      complications, and technical success), while mean difference (MD) and 95% CI were
      pooled for continuous variables (number of needle passes required for diagnosis).
      RESULTS: Eleven RCTs were identified with a total of 694 EUS-FNA cases and 688
      EUS-FNB cases. Compared with EUS-FNA, EUS-FNB had a better specimen adequacy (OR:
      1.83, 95% CI: 1.27-2.64), higher diagnostic accuracy (OR: 1.62, 95% CI: 1.17
      2.26), and fewer number of needle passes (MD: 0.69, 95% CI: 1.18 to 0.20). No
      significant difference was found in complications (OR: 1.01, 95% CI: 0.27-3.78)
      and technical success (OR: 0.13, 95% CI: 0.02-1.07). CONCLUSION: EUS-FNB is
      superior to EUS-FNA in sampling pancreatic masses.

PMID- 29595662
TI  - Difference between elderly and non-elderly patients in using serum lactate level
      to predict mortality caused by sepsis in the emergency department.
AB  - Elderly people are more susceptible to sepsis and experience more comorbidities
      and complications than young adults. Serum lactate is a useful biomarker to
      predict mortality in patients with sepsis. Lactate production is affected by the
      severity of sepsis, organ dysfunction, and adrenergic stimulation. Whether the
      predictive ability of serum lactate will be different between non-elderly and
      elderly patients is unknown.A retrospective cohort study was conducted to compare
      the prognostic value of hyperlactatemia in predicting the mortality between
      elderly (>=65 years) and non-elderly (<65 years) patients with sepsis.This is a
      single-center retrospective observational cohort study conducted from January
      2007 to December 2013 in southern Taiwan. All patients with sepsis, who used
      antibiotics, with blood culture collected, and with available serum lactate
      levels in the emergency department, were included in the analysis. We evaluated
      the difference in serum lactate level between the elderly and non-elderly septic
      patients by using multiple regression models.A total of 7087 patients were
      enrolled in the study. Elderly and non-elderly patients accounted for 62.3%
      (4414) and 40.2% (2673) of all patients, respectively. Statistically significant
      difference of serum lactate levels was not observed between elderly and non
      elderly survivors (2.9 vs 3.0 mmol/L; P = .57); however, elderly patients had
      lower lactate levels than those within the 28-day in-hospital mortality (5.5 vs
      6.6 mmol/L, P < .01). Multiple logistic regression revealed higher adjusted
      mortality risk in elderly and non-elderly patients with lactate levels of >=4.0
      mmol/L (odds ratio [OR], 4.98 and 5.82; P < .01, respectively), and lactate level
      between 2 and 4 mmol/L (OR, 1.57 and 1.99; P < .01, respectively) compared to
      that in the reference group with lactate levels of <2.0 mmol/L in each group. In
      receiver operating characteristic curve analysis, sensitivity rates for
      predicting mortality were 0.80 and 0.77 for non-elderly and elderly patients,
      respectively, by using serum lactate levels higher than 2.0 mmol/L.Septic elderly
      non-survivors had 1 mmol/L lower serum lactate level than those of the non
      elderly non-survivors. Lactate >2 mmol/L still could provide enough sensitivity
      in predicting sepsis mortality in elder patients.

PMID- 29595663
TI  - Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: This meta-analysis aims to examine whether the MspI and Ile462Val
      polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer
      risk. METHODS: Eligible case-control studies were identified dated until July
      2017. Pooled odds ratios (ORs) were used to assess the strength of the
      association between the two variants and cervical cancer risk. RESULTS: Thirteen
      studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism
      and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val
      polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any
      genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] =
      1.16-1.79; heterozygous model: OR = 1.40, 95% CI = 1.08-1.82; homozygous model:
      OR = 2.22, 95% CI = 1.48-3.33, dominant model: OR = 1.50, 95% CI = 1.14-1.98 and
      recessive model: OR = 1.80, 95% CI = 1.35-2.41); similar significantly increased
      risk was found among Caucasians and Asians. Ile462Val polymorphism was associated
      with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI =
      1.27-2.67; heterozygous model: OR = 1.42, 95% CI = 1.28-1.61; homozygous model:
      OR = 2.94, 95% CI = 1.15-7.54; dominant model: OR = 2.00, 95% CI = 1.33-3.00);
      this finding was replicated upon Caucasian population. CONCLUSION: This meta
      analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were
      risk factors for developing cervical cancer.

PMID- 29595664
TI  - Roles of T follicular helper cells in the pathogenesis of adenoidal hypertrophy
      combined with secretory otitis media.
AB  - The aim of this study was to investigate the roles of T follicular helper (Tfh)
      cells in secretory otitis media (SOM) combined with adenoidal hypertrophy
      (AH).Patients with AH or AH combined with SOM admitted to the Yancheng No. 1
      People's Hospital from December 2012 to December 2014 were included. Fourteen age
      matched healthy individuals received physical examinations in the hospital served
      as control. The venous Tfh was determined using flow cytometry, and CD3 + CD4 +
      CXCR5 + T lymphocytes were defined as Tfh cells. Serum inflammatory factors
      including IL-8, IL-1b, IL-6, IL-10, TNF, IL-12p70, IL-21, and IgE were determined
      using commercial kits.Compared with the AH group, the number of CD4 + CXCR5 + T
      cells in peripheral blood of the AH combined with SOM group showed significant
      increase. Statistical differences were noticed in the number of the number of CD4
      + CXCR5 + T cells in moderate and severe AH groups compared with that of the
      control group. Statistical differences were identified in the proportion of CD4 +
      CXCR5 + T cells in the adenoidal tissues between the AH combined with SOM group
      and AH group (P < .05). For the CD4 + CXCR5 + T cells in adenoidal tissues, no
      statistical differences were noticed between the moderate and severe AH groups (P
      > .05). The number of CD4 + CXCR5 + T cells was positively correlated to the
      serum IL-21. Nevertheless, no correlation was noticed between CD4 + CXCR5 + T
      cell and serum IL-8, IL-6, IL-10, and IgE.Tfh is involved in the AH combined with
      SOM in children. Besides, serum IL-21, IL-8, IL-6, IL-10, and IgE may be involved
      in the onset of SOM in children.

PMID- 29595665
TI  - Saddle embolism treated by thrombolysis and thrombus aspiration via bilateral
      femoral artery puncture catheter: A case report.
AB  - INTRODUCTION: Abdominal aortic saddle embolism is a rare and severe disease with
      the manifestation of abrupt onset, rapid progression and high mortality.
      Endovascular therapy becomes a new option for this disease due to its minor
      trauma, less complications, no requirement for general anesthesia or abdominal
      incisions, and shorter hospitalization duration. METHODS: A 50-year-old female
      was diagnosed as abdominal aortic saddle embolism, and thrombus aspiration was
      given immediately via bilateral femoral artery puncture catheter along with
      artery indwelling catheter thrombolysis. RESULTS: The saddle embolism was removed
      completely. After 1-month follow-up, the computed tomography angiography (CTA)
      examination showed neither stenosis nor thrombus in the abdominal aorta and iliac
      artery. The patient achieved perfect outcome. CONCLUSIONS: Endovascular therapy
      may be an optional solution for saddle embolism.

PMID- 29595666
TI  - Components of metabolic syndrome increase the risk of mortality in nonalcoholic
      fatty liver disease (NAFLD).
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in the United States. Metabolic syndrome (MS) components are highly
      prevalent in NAFLD. Our aim is to assess the relationship of NAFLD and MS with
      long-term outcome of mortality.The Third National Health and Nutrition
      Examination Survey (NHANES) was utilized. NAFLD was diagnosed by ultrasound in
      the presence of hepatic steatosis and no other causes of chronic liver disease.
      History of MS and its components were obtained from self-reported NHANES
      questionnaires. Mortality was obtained from Mortality-Linkage File, through
      December 31, 2011. Chi-square test was used for categorical variables and Cox
      proportional models estimated hazard ratios with 95% confidence interval.NAFLD
      cohort (n = 3613) had a median age of 43 years, 73% white, and 50% male. NAFLD
      group with at least one MS condition was significantly older, had higher body
      mass index, more likely to have insulin resistance, and heart disease compared to
      NAFLD group without MS. Over 19-years of follow-up, 1039 people died. Compared to
      NAFLD patients without MS, presence of one MS component increased the risk of
      mortality at 8-year (2.6% vs 4.7%) and 16-year (6% vs 11.9%) (P < .001). After
      adjusting for socio-demographic factors, NAFLD with all MS components was
      associated with overall, cardiac and liver-mortality. Increased number of MS
      components was associated with lower survival (P < .0001).Patients with NAFLD and
      MS have higher mortality risk compared to NAFLD patients without MS. These NAFLD
      patients should be prioritized for the development of treatment regimens.

PMID- 29595667
TI  - Association between BACE1 gene polymorphisms and focal seizures in a Chinese Han
      population.
AB  - BACKGROUND: Beta-secretase 1 (BACE1) is attracting increasing attention for its
      vital role in pathogenesis of many neuropsychiatric disorders and many studies
      also have indicated BACE1 as a possible risk factor for seizures, but not any
      studies have reported association between BACE1 gene polymorphisms and seizures.
      Therefore, we investigated the possible association between focal seizures and
      BACE1 gene polymorphisms in the present study. METHODS: A total of 162 patients
      and 211 health controls were enrolled in this study and polymorphisms of BACE1
      gene were detected using polymerase chain reaction (PCR)-ligase detection
      reaction method. RESULTS: The frequency of genotype AT for BACE1 rs535860 (A>T)
      was significantly higher (24.1%) in patients compared to controls (14.7%) (OR =
      1.836, 95% CI = 1.086-3.102, P = .023). Intriguingly, we only found the
      significant difference of BACE1 SNP genotype and allele frequency among males but
      not females. However, no statistically significant results were presented for the
      genotype distributions of rs525493 (G>T) and rs638405(C>G) polymorphisms between
      patients and controls. CONCLUSION: Our study demonstrated there may exist an
      association between BACE1 rs535860 (A>T) polymorphism and focal seizures in
      Chinese Han males.

PMID- 29595668
TI  - Fennel (Foeniculum vulgare) on management of menopausal symptoms: A protocol for
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Fennel (Foeniculum vulgare) is often used in women's health care to
      treat dysmenorrhea, increase the milk supply, and address symptoms of menopause.
      The object of this review is to evaluate the current evidence on the efficacy of
      fennel for the management menopausal symptoms. METHODS AND ANALYSES: Thirteen
      databases will be searched from their inception to the present. These include
      PubMed, AMED, EMBASE, the Cochrane Library, six Korean medical databases (Korean
      Studies Information Service System, DBPIA, the Korean Institute of Science and
      Technology Information, the Research Information Service System, KoreaMed, and
      the Korean National Assembly Library), and 3 Chinese databases (the China
      National Knowledge Infrastructure Database [CNKI], the Chongqing VIP Chinese
      Science and Technology Periodical Database [VIP], and Wanfang Database). Study
      selection, data extraction, and assessments will be performed independently by 2
      researchers. The risk of bias will be assessed using the Cochrane risk of bias
      tool. ETHICS AND DISSEMINATION: Ethical approval is not required, given that this
      protocol is for a systematic review only. The review will be published in a peer
      reviewed journal and disseminated both electronically and in print. The review
      will be updated to inform and guide healthcare practice and policy. TRIAL
      REGISTRATION NUMBER: PROSPERO 2018 CRD42018085698.

PMID- 29595669
TI  - Integrative medicine for managing the symptoms of lupus nephritis: A protocol for
      systematic review and meta-analysis.
AB  - BACKGROUND: Integrative medicine is claimed to improve symptoms of lupus
      nephritis. No systematic reviews have been performed for the application of
      integrative medicine for lupus nephritis on patients with systemic lupus
      erythematosus (SLE). Thus, this review will aim to evaluate the current evidence
      on the efficacy of integrative medicine for the management of lupus nephritis in
      patients with SLE. METHODS AND ANALYSES: The following electronic databases will
      be searched for studies published from their dates of inception February 2018:
      Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL),
      as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced
      Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base],
      the Research Information Service System [RISS], and the Korean Studies
      Information Services System [KISS]), and 1 Chinese medical database (the China
      National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and
      assessment will be performed independently by 2 researchers. The risk of bias
      (ROB) will be assessed using the Cochrane ROB tool. DISSEMINATION: This
      systematic review will be published in a peer-reviewed journal and disseminated
      both electronically and in print. The review will be updated to inform and guide
      healthcare practice and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2018
      CRD42018085205.

PMID- 29595670
TI  - Acupuncture for chronic pelvic inflammatory disease: A systematic review
      protocol.
AB  - BACKGROUND: Chronic pelvic inflammation disease (PID) is a difficult-to-treat
      gynecological disorder with complex etiologies. Acupuncture has been applied
      widely for treating chronic pelvic inflammation or chronic pelvic pain symptoms
      in China. The aim of this review is to undertake a systematic review to estimate
      the effectiveness and safety of acupuncture on chronic PID. METHODS: A literature
      search will be conducted electronically with date up to October 2018 in MEDLINE,
      Cochrane Library, EBASE, and CNKI databases, using combination subject terms of
      chronic pelvic pain (or chronic pelvic inflammation, and chronic pelvic pain
      symptoms, etc.) and acupuncture related treatment. Also duplicates will be
      removed. The primary outcomes consisted of improvement rate and pain relief.
      Secondary outcomes include the recurrence rate and side effects, such as
      pneumothorax, bleeding, serious discomfort, subcutaneous nodules, and infection.
      Systematic reviews and databases will be searched for randomized controlled
      trials on acupuncture for chronic PID with acupuncture treatment will be
      included. Cochrane RevMan V5.3.5 risk of bias assessment tool will be implemented
      for risk of bias evaluation, data synthesis, meta-analyses, and subgroup analysis
      while condition is met. Mean difference (MD), standard mean difference (SMD), and
      dichotomous data will be used to present continuous outcomes. RESULTS: This study
      will generate a comprehensive review of current evidence of acupuncture for
      chronic pelvic inflammation diseases. CONCLUSION: The study will provide updated
      evidence to evaluate the effectiveness and side effects of acupuncture for
      chronic pelvic inflammation disease. PROSPERO REGISTRATION NUMBER:
      CRD42018087950.

PMID- 29595672
TI  - A case report of a man on peritoneal dialysis having intractable hyponatremia.
AB  - RATIONALE: Hyponatremia is one of the most common electrolyte disorders in
      patients on peritoneal dialysis (PD). It can be associated with severe
      consequences, higher morbidity and mortality. Therefore, hyponatremia should be
      assessed and monitored more carefully in these patients. PATIENT CONCERNS: A 55
      year-old male PD patient progressively developed intractable hyponatremia was
      admitted to our hospital. DIAGNOSES: The observation that no significant salt was
      lost in kidney and PD drainage prompted us to seek the underlying reasons for
      malnutrition and chronic inflammation. And cancer and tuberculosis were further
      suspected, although the exact nature at last was not clearly determined due to
      the unfavorable prognosis. INTERVENTIONS: The hyponatremia can hardly be improved
      by adjusting ultrafiltration close to zero, increasing sodium intake from 2.5 g
      to 7g, and nutrition counselling to maintain protein intake 0.9-1.2 g/kg/day and
      calorie intake 27-35 kcal/kg/day. Due to poor general situation, he received
      tentative anti-tuberculosis treatment instead of surgery for intracranial space
      occupying lesion. OUTCOMES: He died at home with conservative therapy. LESSONS:
      It highlighted the challenge for differential diagnosis and treatment in the
      hyponatremia on PD patient.

PMID- 29595671
TI  - Effect of intravenous lidocaine infusion on long-term postoperative pain after
      spinal fusion surgery.
AB  - BACKGROUND: Intravenous lidocaine infusion is known to reduce postoperative pain
      for days or weeks beyond the infusion time, and plasma half-life in several types
      of surgical procedures. OBJECTIVES: To evaluate the effect of intravenous (IV)
      lidocaine infusion on long term postoperative pain intensity for 3 months in
      patients undergoing spinal fusion surgery. STUDY DESIGN: Prospective randomized,
      double-blinded study. SETTING: Assiut University Hospital, Assiut, Egypt.
      METHODS: Forty patients undergoing spinal fusion surgery were randomized into 2
      equal groups (n = 20 in each). Patients in the lidocaine group received IV
      lidocaine at a dosage of 2.0 mg/kg slowly before induction of anesthesia,
      followed by lidocaine IV infusion at a rate of 3.0 mg/kg/h until the end of
      surgery. Patients in the control group received an equal volume of normal saline.
      The following data were assessed: pain by Visual Analog Score (VAS) at 1 hour, 6
      hours, 12 hours, 24 hours, 48 hours, at discharge time, and at 1 month, 2 months,
      and 3 months post-operation, time to first request for additional analgesia, and
      total morphine consumption in 24 hours. RESULTS: Lidocaine significantly reduced
      the postoperative pain score (VAS) for up to 3 months (P < .05), and
      significantly reduced morphine consumption (4.5 mg vs. 19.85 mg) in the 1st 24
      hours postoperative. Lidocaine also significantly, prolonged (P < .05) the time
      to first request for additional analgesia (9.56 +/- 2.06 hours vs 1.82 +/- 0.91
      hours). CONCLUSION: Intra-operative lidocaine, when given intravenously as a
      bolus followed by an infusion, significantly decreased long term postoperative
      back pain intensity in patients undergoing spinal fusion surgery.

PMID- 29595673
TI  - Implants for orthodontic anchorage: An overview.
AB  - Implantanchorage continues to receive much attention as an important orthodontic
      anchorage. Since the development of orthodontic implants, the scope of
      applications has continued to increase. Although multiple reviews detailing
      implants have been published, no comprehensive evaluations have been performed.
      Thus, the purpose of this study was to comprehensively evaluate the effects of
      implants based on data published in review articles.An electronic search of the
      Cochrane Library, Medline, Embase, Ebsco and Sicencedirect for reviews with
      "orthodontic" and "systematic review or meta analysis" in the title, abstract,
      keywords, or full text was performed. A subsequent manual search was then
      performed to identify reviews concerning orthodontic implants. A manual search of
      the orthodontic journals American Journal of Orthodontics and Dentofacial
      Orthopedics (AJODO), European Journal of Orthodontics (EJO), and Angle
      Othodontist was also performed. Such systematic reviews that evaluated the
      efficacy and safety of orthodontic implants were used to indicate success rates
      and molar movements.A total of 23 reviews were included in the analysis. The
      quality of each review was assessed using a measurement tool for Assessment of
      Multiple Systematic Reviews (AMSTAR), and the review chosen to summarize outcomes
      had a quality score of >6. Most reviews were less than moderate quality. Success
      rates of implants ranged in a broad scope, and movement of the maxillary first
      molar was superior with implants compared with traditional anchorage.

PMID- 29595674
TI  - Outcomes of modified trapeziectomy with ligament reconstruction tendon
      interposition for the treatment of advanced thumb carpometacarpal arthritis: Two
      year follow-up.
AB  - Numerous arthroplasty techniques had been reported for the treatment of thumb
      carpometacarpal (CMC) joint osteoarthritis. The purpose of our study is to
      evaluate long-term clinical and radiographic outcomes of patients who underwent
      modified trapeziectomy with ligament reconstruction tendon interposition
      (LRTI).Our retrospective study included 20 consecutive patients with advanced
      thumb CMC arthritis receiving modified trapeziectomy with LRTI (20 thumbs). For
      clinical evaluation, we assessed visual analogue scale (VAS), Disabilities of the
      Arm, Shoulder and Hand (DASH) scores and Kapandji index. Additionally, the grip,
      pinch power and waist flexion power, radial and volar abduction angle were
      evaluated, As for radiologic evaluation, we just estimated height of the
      trapezial space.We took 2-year follow-up. All patients showed decreased VAS from
      6.8 preoperatively to 1.4. Mean DASH and Kapandji scores were improved from 52.2
      preoperatively to 21.6 and from 6.4 preoperatively to 7.4, respectively. Compared
      to preoperative range of motion (ROM) for radial abduction and volar abduction,
      both markedly increased at 2-year follow-up (from 61.2 to 80.1, from 60.6 to
      78.3, respectively). Besides, mean power improved from 15.9 preoperatively to
      21.7 kg at 2-year follow-up for grip power, from 1.9 preoperatively to 3.5 kg at
      2-year follow-up for tip pinch; however, mean waist flexion power showed no
      significant change from 20.5 preoperatively to 19.7 kg at 2-year follow-up.
      Notably, there was no significant sinking in height of the trapezial space from
      10.0 preoperatively to 9.6 mm at 2-year follow-up. NO case had a complication at
      final follow-up.Modified trapeziectomy with LRTI treating thumb CMC arthritis in
      Eaton stage III-IV had a satisfactory efficacy. This new procedure is able to
      provides enough support for thumb to prevents thumb sinking.

PMID- 29595675
TI  - A 12-year analysis of closed medical malpractice claims of the Taiwan civil
      court: A retrospective study.
AB  - Malpractices lawsuits cause increased physician stress and decreased career
      satisfaction, which might result in defensive medicine for avoiding litigation.
      It is, consequently, important to learn experiences from previous malpractice
      claims. The aim of this study was to examine the epidemiologic factors related to
      medical malpractice claims, identify specialties at high risk of such claims, and
      determine clinical which errors tend to lead to medical malpractice lawsuits, by
      analyzing closed malpractice claims in the civil courts of Taiwan.The current
      analysis reviewed the verdicts of the Taiwan judicial system from a retrospective
      study using the population-based databank, focusing on 946 closed medical claims
      between 2002 and 2013.Among these medical malpractice claims, only 14.1% of the
      verdicts were against clinicians, with a mean indemnity payment of $83,350. The
      most common single specialty involved was obstetrics (10.7%), while the surgery
      group accounted for approximately 40% of the cases. In total, 46.3% of the
      patients named in the claims had either died or been gravely injured. Compared to
      the $75,632 indemnity for deceased patients, the mean indemnity payment for
      plaintiffs with grave outcomes was approximately 4.5 times higher. The diagnosis
      groups at high risk of malpractice litigation were infectious diseases (7.3%),
      malignancies (7.2%), and limb fractures (4.9%). A relatively low success rate was
      found in claims concerning undiagnosed congenital anomalies (4.5%) and infectious
      diseases (5.8%) group. A surgery dispute was the most frequent argument in civil
      malpractice claims (38.8%), followed by diagnosis error (19.3%).Clinicians
      represent 85.9% of the defendants who won their cases, but they spent an average
      of 4.7 years to reach final adjudication. Increased public education to prevent
      unrealistic expectations among patients is recommended to decrease frivolous
      lawsuits. Further investigation to improve the lengthy judicial process is also
      necessary to relieve the stress of medical malpractice claims on clinicians and
      practitioners, as well as on the judicial system and rightful claimants.

PMID- 29595676
TI  - A single-center observational study on the efficacy of percutaneous coronary
      intervention for ischemic heart failure: A cohort study.
AB  - The effects of revascularization by percutaneous coronary intervention (PCI) on
      cardiac function and clinical outcomes in patients with confirmed coronary artery
      disease (CAD) and heart failure (HF), on the basis of the optimal medical
      treatment recommended by current guidelines, remain to be determined.A cohort
      study was performed to evaluate the efficacy of PCI on the basis of optimal
      medical treatment in patients with CAD and HF. Patients who received PCI were
      subsequently grouped according to partial and complete revascularization (CR)
      depending on the PCI outcome. The primary outcome was defined as a composite
      outcome of major adverse cardiovascular events (MACEs). Changes in left
      ventricular ejection fraction (LVEF) also were compared.A total of 69 patients
      (12 who received medical treatment and 57 who received PCI) were included.
      Patients in the PCI group showed significantly improved LVEF (P < .001), but
      patients in the medical treatment group did not (P > .05) after 3 months of
      follow-up. MACEs occurred in 50% patients in the medical treatment group and
      19.3% patients of the PCI group, with this difference almost reaching statistical
      significance (P = .06). Compared with patients who received medical therapy only,
      patients who received PCI experienced better survival (P = .02). Moreover,
      survival seemed to be better in patients who achieved CR with PCI of the coronary
      arteries than in those who had partial revascularization of the coronary arteries
      (P = .06).PCI may be effective for improving survival in patients with CAD and
      HF.

PMID- 29595677
TI  - The value of scintigraphy, computed tomography, magnetic resonance imaging, and
      single-photon emission computed tomography/computed tomography for the diagnosis
      of ectopic thyroid in the head and neck: A STROBE-compliant retrospective study.
AB  - Because of its rarity, the exact imaging features of ectopic thyroid are poorly
      known.To analyze the value of scintigraphy, computed tomography (CT), magnetic
      resonance imaging (MRI), and single-photon emission computed tomography
      (SPECT)/CT in the diagnosis of ectopic thyroid in the head and neck.First, we
      retrospectively analyzed the scintigraphy, CT, MRI, and SPECT/CT images from 25
      masses (22 patients) suspected of head and neck ectopic thyroid from 2006 to 2017
      at the Shanghai Ninth People's Hospital. Each mass was imaged by nuclear imaging
      (scintigraphy with or without SPECT/CT) and radiological exam (CT and/or MRI).
      Pathological examination was considered as the gold standard. Secondly, thirteen
      malignant ectopic thyroids in the head and neck reported in the English
      literature from 2001 to 2017 were retrieved for comparison.The accuracy of
      scintigraphy was not significantly higher than that of CT (94.7%, vs 89.5%, P >
      .99) or MRI (92.3%, vs 84.6%, P > .99). Five masses which underwent scintigraphy
      with SPECT/CT were all true positive, while 1 was false negative on MRI, and 2
      were false negative on CT. Compared to the benign ectopic thyroids in our study,
      the 13 malignant ectopic thyroids retrieved from the literature were grossly the
      same in shape, margins, and invasion on CT or MRI.The number of patients was
      limited, but scintigraphy combined with SPECT/CT could be a reliable method for
      the diagnosis of ectopic thyroid. Benign and malignant ectopic thyroids appear to
      be similar in shapes, margins, and invasion on CT or MRI.

PMID- 29595678
TI  - Early changes in fibrinogen after administration of alteplase are associated with
      the short-term efficacy of thrombolysis.
AB  - The authors aimed to determine whether early changes in fibrinogen were
      associated with the efficacy of intravenous thrombolysis at 24 hours after
      alteplase infusion. The authors retrospectively reviewed a consecutive series of
      56 patients with acute ischemic stroke treated with alteplase in the clinical
      database. The fibrinogen levels were monitored at the first and fourth hours
      after alteplase infusion. Additionally, the National Institutes of Health Stroke
      Scale (NIHSS) scores were recorded to define the short-term efficacy of
      intravenous thrombolysis before and 24 hours after alteplase infusion. The
      patients were distributed into amelioration, deterioration, and inefficiency
      groups according the short-term efficacy of intravenous thrombolysis. One-way
      ANOVA and post hoc analysis were used to compare the differences in the clinical
      characteristics among these groups. The relationships among changes in the
      fibrinogen levels, other potential risk factors, and NIHSS scores were examined
      using logistic regression analysis. Fifty-two patients (mean age, 65.71 +/- 11.04
      years; male, 57.7%) were finally enrolled in the study. The median NIHSS of these
      patients was 11 (range, 2-23), and the mean time from symptom onset to
      thrombolysis was 187.17 +/- 67.53 minutes. The frequency of hypertension in the
      deterioration group was significantly higher than that in the inefficiency group
      (P = .01). Changes in the fibrinogen level were more significant in the
      amelioration group than in the other groups (P < .05). Logistic regression
      analysis revealed that changes in the fibrinogen levels between the first and
      fourth hours were positively associated with the short-term efficacy of alteplase
      infusion (odds ratio, 3.98; 95% confidence interval, 1.56-10.16; P = .004). Early
      changes in fibrinogen levels may be a potential predictor for the short-term
      efficacy of alteplase treatment in acute ischemic stroke. Additionally, these
      changes may be helpful for determining the short-term efficacy of alteplase
      treatment and early therapeutic strategies in clinical practice.

PMID- 29595680
TI  - Assessment of the periodontal health status in patients undergoing orthodontic
      treatment with fixed appliances and Invisalign system: A meta-analysis.
AB  - BACKGROUND: At present, many scholars have studied the periodontal health status
      of patients undergoing orthodontic treatment with fixed appliances and
      invisalign. However, those results are inconsistent. Therefore, we conducted this
      meta-analysis, and then provide reference for clinical treatment. METHODS: Most
      databases, such as the Cochrane Library, EMBASE, PubMed, Medline, Chinese
      Biomedical Literature Database, CNKI, and Wan Fang Data were retrieved for
      related articles from the establishment of the database to October 2017.
      Meanwhile, we also searched the references of the related literatures manually,
      in order to increase the included literatures. Two researchers screened the
      related literatures according to the inclusion criteria and exclusion criteria.
      Stata 12.0 software was used for data analysis, and results are estimated by odds
      ratio (OR) and 95% confidence interval (CI). RESULTS: Finally, 7 articles,
      including 368 patients, were included into our meta-analysis. Meta-analysis
      results showed that there was no statistically significant difference of gingival
      index (GI) and sulcus probing depth (SPD) status between the invisalign group and
      the control group, including at 1, 3, and 6 months (all P > .05). When compared
      with the control group, the invisalign group presented a lower plaque index (PLI)
      and sulcus bleeding index (SBI) status at 1 month (OR = -0.53, 95% CI: -0.89 to 
      0.18; OR = -0.44, 95% CI: -0.70 to -0.19, respectively), 3 months (OR = -0.69,
      95% CI: -1.12 to -0.27; OR = -0.49, 95% CI: -0.93 to -0.05, respectively), and 6
      months (OR = -0.91, 95% CI: -1.47 to -0.35; OR = -0.40, 95% CI: -0.63 to -0.07,
      respectively). Subgroup analysis showed that the SPD status was lower in the
      invisalign group at 6 months when measured the teeth using Ramfjord index (OR = 
      0.74, 95% CI: -1.35 to -0.12). However, there was no statistically significant
      difference between the 2 groups when using other measure methods (OR = 0.12, 95%
      CI: -0.26 to 0.17). CONCLUSION: Our meta-analysis suggests that comparing with
      the traditional fixed appliances, patients treated with invisalign have a better
      periodontal health. However, more studies are needed to confirm this conclusion
      in the future.

PMID- 29595681
TI  - Value of free/total prostate-specific antigen (f/t PSA) ratios for prostate
      cancer detection in patients with total serum prostate-specific antigen between 4
      and 10 ng/mL: A meta-analysis.
AB  - BACKGROUND: Prostate carcinoma is a common disease that occurs in men over 50
      years old. Many studies have explored the effect of free/total prostate-specific
      antigen (f/t PSA) ratio in monitoring prostate cancer. We conducted a meta
      analysis to identify the accuracy of the f/t PSA ratio in the diagnosis of
      prostate cancer in patients who have PSA levels of 4 to 10 ng/mL. METHODS:
      Databases searched included PubMed and OVID databases, from inception to March
      2017, after a systematical review, sensitivity, specificity, and other measures
      of accuracy of the f/t PSA ratio in the diagnosis of prostate cancer were pooled.
      We used summary receiver operating characteristic curves to summarize overall
      test performance. RESULTS: Fifteen case-control studies from 14 articles were
      identified. The results indicated that the sensitivity of the f/t PSA ratio in
      the diagnosis of prostate cancer ranged from 0.5 to 0.94 (pooled sensitivity
      0.70, 95% CI: 0.67-0.72), whereas its specificity ranged from 0.31 to 0.93
      (pooled specificity 0.55, 95% CI: 0.57-0.60). The positive likelihood ratio was
      1.85 (95% CI: 1.56-2.20), negative likelihood ratio was 0.42 (95% CI: 0.34-0.53),
      and diagnostic odds ratio was 4.81 (9.53% CI: 3.33-6.94). CONCLUSIONS: The f/t
      PSA ratio determination has a low sensitivity and specificity for the diagnosis
      of prostate cancer; it would not be useful for the diagnosis of prostate cancer
      by itself. The results of f/t PSA ratio measurements should refer to the clinical
      manifestations and the results of conventional tests such as biopsies.

PMID- 29595679
TI  - Central nervous system histoplasmosis: Multicenter retrospective study on
      clinical features, diagnostic approach and outcome of treatment.
AB  - Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with
      disseminated histoplasmosis. Most experience has been derived from small single
      center case series, or case report literature reviews. Therefore, a larger study
      of central nervous system (CNS) histoplasmosis is needed in order to guide the
      approach to diagnosis, and treatment.A convenience sample of 77 patients with
      histoplasmosis infection of the CNS was evaluated. Data was collected that
      focused on recognition of infection, diagnostic techniques, and outcomes of
      treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma
      antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid
      (CSF) in 75% of patients. One year survival was 75% among patients treated
      initially with amphotericin B, and was highest with liposomal, or deoxycholate
      formulations. Mortality was higher in immunocompromised patients, and patients 54
      years of age, or older. Six percent of patients relapsed, all of whom had the
      acquired immunodeficiency syndrome (AIDS), and were poorly adherent with
      treatment.While CNS histoplasmosis occurred most often in immunocompromised
      individuals, a significant proportion of patients were previously, healthy. The
      diagnosis can be established by antigen, and antibody testing of the CSF, and
      serum, and antigen testing of the urine in most patients. Treatment with
      liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole
      for at least 1 year, results in survival among the majority of individuals.
      Patients should be followed for relapse for at least 1 year, after stopping
      therapy.

PMID- 29595682
TI  - Salvage preoperative embolization of an infratemporal solitary fibrous tumor: A
      case report with review of the literature.
AB  - RATIONALE: Head and Neck Solitary fibrous tumors (SFT) are very rare. They could
      be misdiagnosed as hemangiopericytomas (HPC). PATIENT CONCERNS: We report a 60 y
      o lady presenting with sinonasal mass, causing recurrent profuse bleeding.
      DIAGNOSES: Hemangioperocytomas versus SFT were among the differentials, according
      to Radiological studies. Upon Biopsy, the diagnosis of SFT has been adopted.
      INTERVENTIONS: Salvage pre-operative embolization resulted in bleeding control,
      bridging the patient to surgery. OUTCOMES: Post-operative course was uneventful,
      and patient symptoms resolved. LESSONS: This is the first case report of a
      sinonasal SFT, where pre-operative embolization has been employed as a salvage
      procedure. This treatment modality is promising, since it controls bleeding,
      bridges patient to surgery and decreases blood loss during the surgical
      procedure.

PMID- 29595683
TI  - Mapping the human brain during a specific Vojta's tactile input: the ipsilateral
      putamen's role.
AB  - A century of research in human brain parcellation has demonstrated that different
      brain areas are associated with functional tasks. New neuroscientist perspectives
      to achieve the parcellation of the human brain have been developed to know the
      brain areas activation and its relationship with different stimuli. This
      descriptive study aimed to compare brain regions activation by specific tactile
      input (STI) stimuli according to the Vojta protocol (STI-group) to a non-STI
      stimulation (non-STI-group). An exploratory functional magnetic resonance imaging
      (fMRI) study was performed. The 2 groups of participants were passively
      stimulated by an expert physical therapist using the same paradigm structure,
      although differing in the place of stimulation. The stimulation was presented to
      participants using a block design in all cases. A sample of 16 healthy
      participants, 5 men and 11 women, with mean age 31.31 +/- 8.13 years was
      recruited. Indeed, 12 participants were allocated in the STI-group and 4
      participants in the non-STI-group. fMRI was used to map the human brain in vivo
      while these tactile stimuli were being applied. Data were analyzed using a
      general linear model in SPM12 implemented in MATLAB. Differences between groups
      showed a greater activation in the right cortical areas (temporal and frontal
      lobes), subcortical regions (thalamus, brainstem, and basal nuclei), and in the
      cerebellum (anterior lobe). STI-group had specific difference brain activation
      areas, such as the ipsilateral putamen. Future studies should study clinical
      implications in neurorehabilitation patients.

PMID- 29595684
TI  - Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric
      cancer: A case report.
AB  - RATIONALE: Gastric metastasis from invasive lobular breast cancer is relatively
      rare, commonly presented among multiple metastases, several years after primary
      diagnosis of breast cancer. Importantly, gastric cancer that is synchronously
      presented with lobular breast cancer can be misdiagnosed as primary gastric
      cancer; therefore, accurate differential diagnosis is required. PATIENT CONCERNS:
      A 39-year-old woman was visited to our hospital because of right breast mass and
      progressive dyspepsia. DIAGNOSES: Invasive lobular carcinoma of breast was
      diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at
      the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on
      biopsy. Synchronous double primary breast and gastric cancers were considered.
      Detailed pathological analysis focused on immunohistochemical studies of selected
      antibodies, including those of estrogen receptors, gross cystic disease fluid
      protein-15, and caudal-type homeobox transcription factor 2, were studied. As a
      result, gastric lesion was diagnosed as metastatic gastric cancer originating
      from breast. INTERVENTIONS: Right breast conserving surgery was performed, and
      duodenal stent was inserted under endoscopic guidance to relieve the patient's
      symptoms. Systemic chemotherapy with combined administration of paclitaxel and
      trastuzumab was initiated. OUTCOMES: Forty-one months after the diagnosis, the
      patient is still undergoing the same therapy. No recurrent lesion has been
      identified in the breast and evidence of a partial remission of gastric wall
      thickening has been observed on follow-up studies without new metastatic lesions.
      LESSONS: Clinical suspicion, repeat endoscopic biopsy, and detailed histological
      analysis, including immunohistochemistry, are necessary for diagnosis of
      metastatic gastric cancer from the breast.

PMID- 29595685
TI  - Double-blind placebo-controlled randomized clinical trial on the use of
      paracetamol for performing mammography.
AB  - BACKGROUND: This study was conducted within the Goias Mastology Research Network.
      To verify the possibility of diminishing pain, and discomfort during the
      mammography using analgesic administration. METHODS: Randomized, double-blinded,
      placebo controlled trial, testing paracetamol to diminish the pain, and
      discomfort during mammography. Three hundred patients who came for screening
      mammography were randomized for this study. A questionnaire with 2 parts was
      used: the first had questions that concerned the patient identification, and
      factors related to the pain during mammography; and the second asked about the
      scale of discomfort (no discomfort; uncomfortable; very uncomfortable;
      intolerable), and the pain (analogical linear scale) during the mammography. Each
      patient received 1000 mg of paracetamol, or placebo. Afterwards each patient
      filled out the second part of the questionnaire. Six patients were excluded from
      the analysis; this resulted in 149 in the paracetamol group, and 145 in the
      placebo group. RESULTS: The 2 groups were homogenous concerning the mean of the
      ages, weight, height, and breast size. The mean of the pain was 3.5 in the
      paracetamol, and 2.8 in the placebo group (P = .12). There were fewer women
      experiencing mild pain in the paracetamol group when compared with those in
      placebo group (relative risk [RR] 0.76, confidence interval [CI] 95% 0.52-0.98).
      There was no significant difference between the 2 groups, according to the
      degrees of discomfort (P =  .69). CONCLUSION: The use of paracetamol can reduces
      the mild pain for women undergoing mammography.

PMID- 29595686
TI  - Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress
      induced cardiomyopathy in sepsis or septic shock: A comparative retrospective
      study.
AB  - While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced
      cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of
      the 2 diseases is different, and they require different treatment strategies.
      Thus, we aimed to investigate risk factors and outcomes between the 2
      diseases.This retrospective study enrolled patients diagnosed with sepsis or
      septic shock, admitted to intensive care unit via emergency department in Korea
      University Anam Hospital, and who underwent transthoracic echocardiography within
      the first 24 hours of admission.In all, 25 patients with SIMD and 27 patients
      with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of
      heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in
      the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines
      were similar. Serum troponin level was significantly elevated in the SICMP and
      SIMD group compared to the control group. N-terminal pro-brain natriuretic
      peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared
      to the SICMP group or control group. The in-hospital mortality rate in the SIMD
      and SICMP group was about 40%, showing increased trends compared with the control
      group. The in-hospital mortality rate was significantly increased in SIMD group
      with EF<30% than in SICMP group with EF<30%. In multiple logistic regression
      analysis, a past history of diabetes mellitus (DM) and HF was significantly
      associated with the incidence of SIMD. Younger age, elevated levels of NT pro
      BNP, and positive result of blood culture also showed significant odds ratio
      regard to the occurrence of SIMD. However, only elevated lactate and troponin
      level were positively associated with the incidence of SICMP.The SIMD and SICMP
      had different risk factors. The risk factors of SIMD were younger age, history of
      DM, history of HF, elevated NT pro-BNP, and positive result of blood culture. The
      elevated levels of lactate and troponin were identified as risk factors of SICMP.
      More importantly, in-hospital mortality rate from SIMD and SICMP showed increased
      trend and worse outcome in SIMD group with reduced EF<30%. Thus, developing SIMD
      or SICMP reflected poor prognosis in sepsis or septic shock.

PMID- 29595687
TI  - Effectiveness and safety of Glycyrrhizae Decoction for Purging Stomach-Fire in
      Behcet disease patients: Study protocol for a randomized controlled and double
      blinding trail.
AB  - BACKGROUND: Behcet disease (BD) is a worldwide-occurred autoimmune disorder and
      currently lack of optional successful treatment. An ancient traditional Chinese
      medical formula called Glycyrrhizae Decoction for Purging Stomach-Fire (GDPSF)
      was recorded and nowadays has been observed to be effective for BD patients.
      However, the strict randomized controlled and double-blinding trail is needed to
      further assess this alternative medicine. METHODS: To ascertain the potential
      effects and safety of GDPSF for BD patients and to determine whether combination
      application of GDPSF and thalidomide could possibly reduce the side effects and
      increase effectiveness for BD management, we will conduct a randomized, double
      blind, controlled clinical trial. Patients enrolled will be randomly assigned
      into 3 groups: GDPSF group, thalidomide group, and integrative group (treated by
      both GDPSF and thalidomide). Participants will receive treatment for 6 months and
      accept a 12 months follow-up. Before and after treatment, clinical
      manifestations, blood tests, thalidomide dosage, remission levels, quality of
      life, and satisfactory levels will be assessed. The data of assessments on each
      group before and after treatments will be collected and analyzed through
      historical control, while between groups through intergroup control. Then
      statistical analysis will be applied to assess the effects and safety.
      DISCUSSION: This study protocol will assess the effects and safety of GDPSF for
      BD patients GDPSF. Combination application of GDPSF and thalidomide might be a
      new integrative medical method for BD patients. TRIAL REGISTRATION: Chinese
      Clinical Registry (ChiCTR-ONC-16009621) on Oct. 2016
      http://www.chictr.org.cn/showproj.aspx?proj=16395.

PMID- 29595688
TI  - Herbal medicine for idiopathic central precocious puberty: A protocol for a
      systematic review of controlled trials.
AB  - BACKGROUND: Herbal medicine is widely used in East Asia to treat idiopathic
      central precocious puberty (ICPP). Most of the available clinical trials that
      investigated herbal medicine for ICPP have been included in this review. This
      systematic review will assess the efficacy and safety of herbal medicine for
      ICPP. METHODS: Eleven databases, including Asian databases, will be searched for
      studies conducted through 2018. We will include randomized controlled trials
      assessing herbal medicine for ICPP. The risk of bias will be evaluated using the
      Cochrane risk of bias assessment tool, and confidence in the cumulative evidence
      will be evaluated using the Grading of Recommendations Assessment, Development,
      and Evaluation instrument. ETHICS AND DISSEMINATION: This systematic review will
      be published in a peer-reviewed journal and disseminated both electronically and
      in print. The review will be updated to inform and guide health care practices.
      TRIAL REGISTRATION NUMBER: PROSPER 2018 CRD42018087988.

PMID- 29595689
TI  - Single-port surgery (SPS) strategy for small bowel obstruction (SBO) caused by
      postoperative internal hernia: A series case report.
AB  - RATIONALE: Internal hernia due to postoperative adhesions sometimes causes small
      bowel obstruction (SBO) and requires emergency surgery. The difficulties in the
      management of SBO with internal hernia include accurate diagnosis and estimation
      of its ischemic degree and of the risk of SBO recurrences following the surgical
      procedure. Laparoscopic surgery is a noninvasive to reduce postoperative
      adhesions and therefore has been widely used recently. However, surgeons often
      tend to hesitate in applying laparoscopic surgery for SBO because of some
      situational disadvantages such as poor operating space or iatrogenic bowel
      injury. Hence, laparoscopic surgery is still not yet the standard procedure for
      SBO caused by internal hernia. Thus, the establishment of an appropriate
      procedure for SBO due to internal hernia is required. PATIENT CONCERNS: We
      experienced 3 SBO cases caused by postoperative internal hernia. The first
      patient was a 59-year-old man who had temporary loop-ileostomy for a perforated
      sigmoid colon due to diverticulitis. Severe hypogastralgia and vomiting occurred
      suddenly on the 33rd postoperative day. The second patient was an 81-year-old man
      who had been hospitalized due to epigastralgia of unknown origin. He had a
      surgical history of omentum patching for a perforated duodenum 20 years ago. The
      third patient was a 72-year-old female who presented at our hospital after sudden
      and severe hypogastralgia. She had a surgical history of sigmoidectomy for her
      sigmoid colon cancer 22 years ago. DIAGNOSIS: A contrast computed tomography (CT)
      revealed a suspected closed loop obstruction of their bowels and immediate
      surgical treatments were required. INTERVENTION: We tried SPS using the surgical
      glove method as an initial approach for their SBO caused by postoperative
      internal hernia. OUTCOMES: Two of these 3 cases completely underwent SPS
      treatment, which afforded accurate diagnosis of SBO. Laparotomy following SPS,
      which allowed accurate diagnosis, was judged to be appropriate and was performed
      in the third case. All the patients were discharged without any complications and
      SBO have not recurred after their discharge. Finally, we established a new
      strategy using SPS for SBO with internal hernia. LESSONS: Our experience suggests
      that SPS is a promising strategy as an initial surgical approach for SBO with
      internal hernia.

PMID- 29595691
TI  - Clinical application of MRI-respiratory gating technology in the evaluation of
      children with obstructive sleep apnea hypopnea syndrome: Erratum.

PMID- 29595690
TI  - A novel index including SNPs for the screening of nonalcoholic fatty liver
      disease among elder Chinese: A population-based study.
AB  - Presently noninvasive methods were employed to the diagnosis of nonalcoholic
      fatty liver disease (NAFLD), including fatty liver index (FLI), hepatic steatosis
      index (HSI), product of fasting triglyceride and glucose levels (TyG), and single
      nucleotide polymorphism (SNP), whereas the accuracy of those indexes need to be
      improved. Our study aimed to investigate the feasibility of a new index
      comprehensive index (CI), consisting of 6 serum biomarkers and anthropometric
      parameters through multivariate logistic regression analysis, to the earlier
      detection of NAFLD, and the diagnostic value of 5 SNPs (S1: rs2854116 of
      apolipoprotein C3 [APOC3], S2: rs4149267 of ATP-binding cassette transporter
      [ABCA1], S3: rs13702 of lipoprotein lipase [LPL], S4: rs738409 of protein 3
      [patatin-like phospholipase domain containing protein 3 (PNPLA3)], S5: rs780094
      of glucokinase regulatory protein gene [GCKR]) for NAFLD were also explored. Area
      under the receiver operating characteristic curves (AUROC) and Youden index (YI)
      were calculated to assess the diagnostic value. The AUROC of CI was higher than
      FLI, HSI, and TyG (CI: 0.897, FLI: 0.873, HSI: 0.855, TyG: 0.793). Therefore, CI
      might be a better index for the diagnosis of NAFLD. Although there had no
      statistical significance (P = .123), the AUROC and YI were increased when CI
      combined with rs2854116 (S1) (AUROC = 0.902, YI = 0.6844). The combination of CI
      with S1 showed even better diagnostic accuracy than CI, which suggests the
      potential value of rs2854116 for the diagnosis of NAFLD.

PMID- 29595692
TI  - Color Doppler ultrasound diagnosis of intrarenal vein thrombosis: A rare case
      report and literature review.
AB  - RATIONALE: We present a case of intrarenal vein thrombosis (IRVT) diagnosed by
      ultrasound (US). To the best of our knowledge, this is the first reported case in
      the imaging literature. PATIENT CONCERNS: A 15-year-old boy with a 4-year history
      of thrombocytopenic purpura presented to the emergency room with a 2-day history
      of sudden-onset severe left flank pain associated with gross hematuria.
      DIAGNOSES: Hypercholesterolemia, proteinuria, and elevated plasma creatinine
      level were present. The US examination showed obscurely structured, sparsely
      distributed arterial and venous flow signals, and an increased resistance index
      (RI) in a localized area. The diagnosis was acute renal failure and nephrotic
      syndrome accompanied by left IRVT. INTERVENTIONS: The patient was treated with
      anticoagulation therapy for 1 month. OUTCOMES: Clinical symptoms were relieved.
      The US re-examination revealed that the arterial flow spectra had returned to
      normal. Also, more venous flow signals were observed in the involved area,
      suggesting thrombolysis. LESSONS: This previously unreported case should alert
      sonographers to include IRVT in the differential diagnosis of flank pain
      associated with hematuria. In such cases, both kidneys and different areas of the
      same kidney should be scanned and compared. Some features, including an obscure
      structure and an increased RI for the involved area indicate possible IRVT.

PMID- 29595693
TI  - Perianal atypical leiomyoma: A case report: Erratum.

PMID- 29595694
TI  - Translation and validation of the Simplified Chinese version of Western Ontario
      Osteoarthritis of the Shoulder Index (WOOS).
AB  - To produce a cross-cultural adaptation and translation of the English version of
      the Western Ontario Osteoarthritis of the Shoulder index (WOOS) into Simplified
      Chinese and to validate its reliability, validity, and responsiveness.A total of
      52 consecutive patients were included. The inclusion criteria were as follows:
      diagnosed to have primary shoulder osteoarthritis (OA) and referred to undergo
      conservative treatment, able to speak Chinese, and able to read Simplified
      Chinese. WOOS, the Oxford Shoulder Score (OSS), and Short Form 36 (SF-36) were
      filled at the first visit, and WOOS alone was filled at the second visit with an
      interval of 3 to 7 days after the first visit. Four months after appropriate
      treatments, the WOOS was again sent to patients by e-mail for the evaluation of
      responsiveness.The intraclass correlation coefficient ranged from 0.90 to 0.98,
      which showed good test-retest reliability. As we had hypothesized, construct
      validity was high according to a significant correlation among WOOS, SF-36 (3
      subscales, namely physical functioning, bodily pain, and role-physical), and OSS.
      High responsiveness was documented by the evaluation of standard response mean
      (from 1.09 to 1.33) and effect size (from 0.80 to 0.97).The Simplified Chinese
      version of WOOS (SC-WOOS) was shown to be a reliable, valid instrument for
      evaluating the quality of life of patients suffering from shoulder OA in China.

PMID- 29595695
TI  - Comamonas kerstersii bacteremia in a patient with acute perforated appendicitis:
      A rare case report.
AB  - RATIONALE: Comamonas species are rarely associated with human infections. Recent
      reports found that Comamonas kerstersii was associated with severe diseases such
      as abdominal infection and bacteremia. However, C. kerstersii maybe be confused
      with Comamonas testosteroni using the automatic bacterial identification systems
      currently available. PATIENT CONCERNS: A 31-year-old man who had onset of left
      upper abdominal pain developed clinical manifestations of right lower abdominal
      pain and classic migration of pain at the temperature of 39 degrees C. The
      positive strain of aerobic and anaerobic bottles of blood cultures was
      identified. DIAGNOSES: The patient was diagnosed as acute peritonitis and
      perforated appendix with abdominal abscess. INTERVENTIONS: The bacterium was
      identified by routine methods, MALDI-TOF-MS and PCR amplification of the 16S
      rRNA. The patient was treated with exploratory laparotomy, appendectomy, tube
      drainage, and prescribing antibiotic treatment. OUTCOMES: The patients were
      discharged with complete recovery. The organisms were confirmed as C. kerstersii
      by MALDI-TOF-MS and a combination of the other results. LESSONS: Our findings
      suggest that C. kerstersii infection occurs most often in association with
      perforated appendix and bacteremia. We presume that C. kerstersii is an
      opportunistic pathogen or commensal with the digestive tract and appendix
      bacteria.

PMID- 29595696
TI  - Point-of-care ultrasound versus auscultation in determining the position of
      double-lumen tube.
AB  - This study was designed to assess the accuracy of point-of-care ultrasound in
      determining the position of double-lumen tubes (DLTs).A total of 103 patients who
      required DLT intubation were enrolled into the study. After DLTs were tracheal
      intubated in the supine position, an auscultation researcher and ultrasound
      researcher were sequentially invited in the operating room to conduct their
      evaluation of the DLT. After the end of their evaluation, fiberscope researchers
      (FRs) were invited in the operating room to evaluate the position of DLT using a
      fiberscope. After the patients were changed to the lateral position, the same
      evaluation process was repeated. These 3 researchers were blind to each other
      when they made their conclusions. Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy were obtained by statistical
      analysis.When left DLTs (LDLTs) were used, the accuracy of ultrasound (84.2%
      [72.1%, 92.5%]) was higher than the accuracy of auscultation (59.7% [45.8%,
      72.4%]) (P < .01). When right DLTs (RDLTs) were used, the accuracy of ultrasound
      (89.1% [76.4%, 96.4%]) was higher than the accuracy of auscultation (67.4%
      [52.0%, 80.5%]) (P < .01). When LDLTs were used in the lateral position, the
      accuracy of ultrasound (75.4% [62.2%, 85.9%]) was higher than the accuracy of
      auscultation (54.4% [40.7%, 67.6%]) (P < .05). When RDLT were used, the accuracy
      of ultrasound (73.9% [58.9%, 85.7%]) was higher than the accuracy of auscultation
      (47.8% [32.9%, 63.1%]) (P < .05).Assessment via point-of-care ultrasound is
      superior to auscultation in determining the position of DLTs.

PMID- 29595697
TI  - Rare cardiac metastasis of soft tissue sarcoma: A case report and literature
      review.
AB  - RATIONALE: Owing to the unique structure and function of the heart, tumor
      metastasis in the heart is rare. Accordingly, no unique symptoms have yet been
      identified for cardiac metastasis. PATIENT AND CONCERNS: A patient presented with
      cardiac metastasis 3 years after surgical resection of alveolar soft tissue
      sarcomas in their late stage. DIAGNOSIS: Ultrasonography showed a middle-high
      echo clump on the left surface of the mid-upper interventricular septum, which
      had an unclear boundary with the myocardium. Meanwhile, blood flow was found in
      the clump, with no blockage of blood flow having been observed. LESSONS: Although
      cardiac metastasis in terminal cancer patients always carries a poor prognosis,
      there is still no effective treatment for cardiac metastasis. In the clinic, it
      is important to improve the patient's quality of life, reduce symptoms and signs,
      and extend the duration of survival.

PMID- 29595698
TI  - Identification of key genes and miRNAs associated with carotid atherosclerosis
      based on mRNA-seq data.
AB  - This study was aimed to explore the crucial genes and microRNAs (miRNAs)
      associated with the carotid atherosclerosis (CA).Two public datasets GSE28829 and
      GSE43292 were obtained from Gene Expression Omnibus databases to analyze the
      differentially expressed genes (DEGs) between primary and advanced
      atherosclerotic plaque tissues. The Gene Ontology (GO) terms, pathways, and
      protein-protein interactions (PPIs) of these DEGs were analyzed. miRNAs and
      transcription factor (TF) were predicted.A total of 112 upregulated and 179
      downregulated intersection DEGs were identified between 2 datasets. In the PPI
      network, HSP90AB1 (degree = 19), RAP1A (degree = 14), and integrin subunit beta 1
      (ITGB1) had higher degrees. A total of 23 miRNAs were predicted, such as miR-126,
      miR-155, miR-19A, and miR-19B. Four TFs were associated with upregulated DEGs,
      while 10 TFs were identified to be associated with downregulated genes.Our study
      suggests the important roles of HSP90AB1, RAP1A, and integrins proteins of ITGB1,
      ITGA11, ITGA9, and ITGB2 in the progression of CA plaque. Additionally, miR-126,
      miR-155, miR-19B, and miR-19A may be considered as biomarkers of CA.

PMID- 29595699
TI  - Severe bilateral isolated coronary ostial lesions as a rare manifestation of
      radiation-induced cardiac disease A case report.
AB  - RATIONALE: With advances in contemporary radiotherapy techniques, and as cancer
      survival improves, severe isolated coronary ostial disease may develop many years
      following mediastinal radiotherapy, even in the absence of classical
      cardiovascular risk factors. PATIENT CONCERNS: We describe the case of a 73-year
      old woman with previous chest radiotherapy for breast cancer who underwent
      coronary artery bypass graft surgery for severe bilateral coronary ostial
      lesions. DIAGNOSES: Coronary angiography demonstrated severe, isolated bilateral
      coronary ostial lesions. INTERVENTIONS: The patient underwent urgent coronary
      artery bypass graft surgery to treat her critical coronary artery disease.
      OUTCOMES: Intra-operatively, internal mammary arteries were not amenable to
      harvesting due to very dense mediastinal adhesions. Therefore, saphenous vein
      grafts were performed to the left anterior descending, distal left circumflex,
      obtuse marginal and distal right coronary arteries. The patient made a
      satisfactory in-hospital recovery, and was subsequently discharged back to her
      local hospital for rehabilitation. LESSONS: Patients successfully treated with
      mediastinal radiotherapy require careful long-term follow-up for the assessment
      of radiation-induced coronary artery disease. Importantly, mediastinal
      irradiation may preclude internal mammary artery utilization, and thus alter the
      strategy for surgical myocardial revascularization.

PMID- 29595700
TI  - Starting of biological disease modifying antirheumatic drugs may be postponed in
      rheumatoid arthritis patients with multimorbidity: Single center real life
      results.
AB  - The objective of this study was to assess the frequency of comorbidities and
      multimorbidities in rheumatoid arthritis (RA) patients under biologic therapy and
      their effects on biological disease modifying antirheumatic drugs (DMARDs)
      choice, timing, and response.Hacettepe University Biologic Registry (HUR-BIO) is
      single center biological DMARD registry. Cardiovascular, infectious, cancer, and
      other comorbidities were recorded with face to face interviews. Multimorbidity is
      defined as >1 comorbidity. Disease duration, initial date of biological DMARDs,
      initial and overall biological DMARD choice were recorded. Disease activity score
      28 (DAS-28) responses were compared to comorbidity presence and
      multimorbidity.Total of 998 RA patients were enrolled into the study. The mean
      age was 53.1 (12.5) and mean disease duration (standard deviation [SD]) was 11.7
      (7.5) years. At least 1 comorbidity was detected in 689 (69.1%) patients, 375
      (37.9%) patients had multimorbidity. Patients had mean 1.36 +/- 1.32 comorbidity.
      The median durations of first biological DMARDs prescription were 60 (3-552)
      months after RA diagnosis. For multimorbidity patients, the median first
      biological prescription duration was longer than the duration for patients
      without multimorbidity (72 [3-552] vs 60 [3-396] months, P < .001). The
      physicians prescribe tumor necrosis factor inhibitor (TNFi) biological drugs less
      frequently than other biological DMARDs in patients with at least 1 comorbidity
      (66.2% vs 74.5%, P = .007) or multimorbidity (34.6% vs 43.5%, P = .006). Patients
      with comorbidities and multimorbidity achieved DAS-28 remission less frequently
      than patients without comorbidity (31.6% vs 42.6%, P = .012 and 27.2% vs 39.7%, P
      = .001, respectively).In real life, physicians may postpone to prescribe
      biological DMARDs and less frequently choose TNFi biological drugs in patients
      with multimorbidity. Furthermore, comorbidity may have a negative effect on the
      treatment response.

PMID- 29595701
TI  - A challenging diagnosis: Case report of oral metastasis from gastric
      adenocarcinoma mimicking pyogenic granuloma.
AB  - RATIONALE: Oral metastases occur more commonly in bone, but can also manifest in
      soft tissues and eventually resemble a reactive lesion. Few cases of oral
      metastases mimicking reactive lesions in soft tissues have been reported to date.
      PATIENT CONCERNS: We report a metastasis of gastric carcinoma (GC) to the oral
      mucosa without bone involvement in a 43 yom clinically and microscopically
      mimicking a reactive lesion. The patient related that the lesion had 1 month of
      evolution, and the ulcerated area suggested the lesion was related to trauma.
      DIAGNOSES: The histopathological examination of the lesion revealed an exuberant
      granulation tissue with few neoplastic cells, and the initial diagnosis of
      pyogenic granuloma was considered. In a second analysis, clusters of clear cells
      morphologically similar to degenerating mucous cells or macrophages, positive for
      Cytokeratin (CK)-20, and CDX2 were found. At the moment, it was confirmed the
      presence of a primary GC in the patient. INTERVENTIONS: A palliative
      radiotherapy/chemotherapy was started. OUTCOMES: However, the patient died 3
      months after the diagnosis of oral metastasis. LESSONS: This report highlights
      the importance of careful clinical and microscopic examinations in cases of oral
      metastasis that may mimic a reactive lesion.

PMID- 29595702
TI  - Coinfection with 2 Clostridium difficile ribotypes in China: A case report.
AB  - RATIONALE: Clostridium difficile infections (CDIs) have been reported in China,
      but detailed clinical symptoms of coinfection by 2 C difficile ribotypes have not
      been documented. PATIENTS CONCERNS: An 83-year-old male with a 10-day history of
      diarrhea and urinary tract infection was admitted to the hospital. The patient
      had received ofloxacin for several days, but his clinical response was poor.
      Laboratory workup revealed high white blood cell (WBC), serum creatinine (Scr),
      and C-reactive protein (CRP) levels. Based on these abnormal lab results, rapid
      detection of glutamate dehydrogenase and toxin A and B was performed. DIAGNOSIS:
      Severe CDI. INTERVENTIONS: Oral vancomycin was administered for 8 days. OUTCOMES:
      Diarrhea symptoms improved and C difficile culture was negative after oral
      vancomycin administration for 8 days. Clostridium difficile was isolated from 3
      consecutive stool samples at 2-day intervals because the patient was admitted to
      the hospital. Polymerase chain reaction ribotyping revealed ribotype (RT) 017 in
      the first 2 samples and RT 001 in the third sample. RT 017 caused significantly
      higher increases in the levels of WBC, Scr, and CRP than RT 001. LESSONS: It is
      necessary to improve clinicians' awareness of CDI and reduce the severity of CDI
      caused by RT 017 in China.

PMID- 29595703
TI  - The clinical result of arthroscopic bone grafting and percutaneous K-wires
      fixation for management of scaphoid nonunions.
AB  - The purpose of this study is to analyze the clinical results of patients with
      scaphoid nonunion treated with arthroscopic bone grafting and K (Kirschner)-wires
      fixation.We retrospectively reviewed the records of 27 patients with scaphoid
      nonunion who had been treated with arthroscopic bone grafting and K-wires
      fixation method from November 2008 to February 2014. The average patient age was
      35 years. The time from injury to treatment averaged 45 months. The average
      follow-up period was 18 months. Bone union was assessed using serial plain
      radiographs. The functional outcome was evaluated by comparing the modified Mayo
      wrist score with the visual analog scale (VAS) for pain, which were measured at
      the time of preoperation and at final follow-up.Union was achieved in 26 of the
      27 nonunions (96.29%). The average radiologic union time was 10 weeks. The
      average VAS score decreased from 6.38 (range, 3-10) preoperatively to 1.59
      (range, 0-3) at the final follow-up. The average modified Mayo wrist score
      improved from 60.19 preoperatively to 83.46 at the final follow-up. According to
      this score, there were 12 excellent, 6 good, and 9 fair results at the final
      follow-up.Arthroscopic bone grafting and percutaneous K-wires fixation is an
      effective treatment method for a scaphoid nonunion and has the advantages of
      allowing thorough assessment, enabling a comprehensive management approach for
      scaphoid nonunion in a minimally invasive manner, and this method can also be
      used for the scaphoid nonunion with SNAC stage I.

PMID- 29595704
TI  - The role of 3D-printing technology in the diagnosis of Eagle syndrome: A case
      report.
AB  - RATIONALE: Eagle syndrome is a rare clinical condition that can be associated
      with elongation of the styloid process. PATIENT CONCERN: A 55-year-old man was
      presented with vague throat discomfort for several years. DIAGNOSIS: 3
      dimentional (3D) computed tomography (CT) reconstruction, and printing revealed
      bilateral elongated styloid processes. INTERVENTIONS: The patient has been
      treated medically, and continues to demonstrate improvement with conservative
      treatment for 2 years. OUTCOME: We report usefulness of 3D CT and 3D printing
      technology for diagnosis of Eagle syndrome. LESSONS: 3D CT reconstruction, and
      printing are beneficial in determining appropriate surgical strategy, and
      allowing the physician to better explain the lesion, and surgical details to
      patients.

PMID- 29595705
TI  - Treatment of partial thickness hand burn injuries in children with combination of
      silver foam dressing and zinc-hyaluronic gel: Case reports.
AB  - RATIONALE: Burns is a common type of traumatic injury in childhood. Nowadays,
      several wound dressings are available to treat the second-degree hand burns
      conservatively. PATIENT CONCERNS, DIAGNOSES: At the authors' institute, 37
      children were treated conservatively with a special dressing at first
      intervention containing Aquacel Ag foam and Zn-hyaluronic gel to determine their
      effectiveness on partial thickness hand burns. INTERVENTIONS: The dressing was
      checked on the second day, and removed on the sixth or seventh day (unless it had
      spontaneously separated). OUTCOMES: None of the 37 children treated with this
      dressing were diagnosed with wound infection. The authors observed the
      epithelialization of the burned areas on the 6-7th day after primary conservative
      treatment. The dressing efficiently promotes epithelialization in all cases.
      Further advantage of Zn-hyaluronic gel is to enhance cell regeneration and
      inhibits dressing fixation into the wound. LESSONS: Based on the authors'
      experience, with this special combination of wound dressing, a gentle, child
      friendly, cost-effective treatment and excellent wound healing observed with
      favourable cosmetic results.

PMID- 29595706
TI  - Large sliding inguino-scrotal hernia of the urinary bladder: A case report and
      literature review.
AB  - RATIONALE: Sliding inguinal hernias of the urinary bladder are protrusions of the
      bladder through the internal inguinal ring, most of which are insignificant and
      diagnosed intra-operatively. Large inguino-scrotal bladder hernias commonly
      present with lower urinary tract symptoms and may cause severe complications,
      including bladder incarceration or necrosis, bladder hemorrhage, obstructive or
      neurogenic bladder dysfunction, and even renal failure. PATIENT CONCERNS: We
      describe and discuss the clinical findings and management of a 59-year-old man
      who complained of a decrease in scrotal size after voiding and 2-stage voiding
      requiring pressure to the scrotum. DIAGNOSES: The patient was diagnosed
      preoperatively as massive, bilateral, inguinoscrotal hernias, and a large, left
      sided, sliding bladder hernia. INTERVENTIONS: The patient underwent a timely open
      re-peritoneal inguinal herniorrhaphy using a mesh. OUTCOMES: The surgical
      outcomes were good, and no surgical site infection, chronic postoperative
      inguinal pain or recurrence were recorded during the follow-up. LESSONS: Better
      knowledge of this rare condition of large inguino-scrotal sliding bladder hernia
      could help in making a correct diagnosis preoperatively and provide proper
      surgical management timely, so as to reduce delay in treatment and avoid
      potential complications.

PMID- 29595707
TI  - Enhancement of Meditation Analgesia by Opioid Antagonist in Experienced
      Meditators.
AB  - OBJECTIVE: Studies have consistently shown that long-term meditation practice is
      associated with reduced pain, but the neural mechanisms by which long-term
      meditation practice reduces pain remain unclear. This study tested endogenous
      opioid involvement in meditation analgesia associated with long-term meditation
      practice. METHODS: Electrical pain was induced with randomized, double-blind,
      cross-over administration of the opioid antagonist naloxone (0.15-mg/kg bolus
      dose, then 0.2-mg/kg per hour infusion dose) with 32 healthy, experienced
      meditation practitioners and a standardized open monitoring meditation. RESULTS:
      Under saline, pain ratings were significantly lower during meditation (pain
      intensity: 6.41 +/- 1.32; pain unpleasantness: 3.98 +/- 2.17) than at baseline
      (pain intensity: 6.86 +/-1.04, t(31) = 2.476, p = .019, Cohen's d = 0.46; pain
      unpleasantness: 4.96 +/-1.75, t(31) = 3.746, p = .001, Cohen's d = 0.68),
      confirming the presence of meditation analgesia. Comparing saline and naloxone
      revealed significantly lower pain intensity (t(31) = 3.12, p = .004, d = 0.56),
      and pain unpleasantness (t(31) = 3.47, p = .002, d = 0.62), during meditation
      under naloxone (pain intensity: 5.53 +/- 1.54; pain unpleasantness: 2.95 +/-
      1.88) than under saline (pain intensity: 6.41 +/- 1.32; pain unpleasantness: 3.98
      +/- 2.17). Naloxone not only failed to eliminate meditation analgesia but also
      made meditation analgesia stronger. CONCLUSIONS: Long-term meditation practice
      does not rely on endogenous opioids to reduce pain. Naloxone's blockade of opioid
      receptors enhanced meditation analgesia; pain ratings during meditation were
      significantly lower under naloxone than under saline. Possible biological
      mechanisms by which naloxone-induced opioid receptor blockade enhances meditation
      analgesia are discussed.

PMID- 29595708
TI  - Brain-Heart Pathways to Blood Pressure-Related Hypoalgesia.
AB  - OBJECTIVE: High blood pressure (BP) is associated with reduced pain sensitivity,
      known as BP-related hypoalgesia. The underlying neural mechanisms remain
      uncertain, yet arterial baroreceptor signaling, occurring at cardiac systole, is
      implicated. We examined normotensives using functional neuroimaging and pain
      stimulation during distinct phases of the cardiac cycle to test the hypothesized
      neural mediation of baroreceptor-induced attenuation of pain. METHODS: Eighteen
      participants (10 women; 32.7 (6.5) years) underwent BP monitoring for 1 week at
      home, and individual pain thresholds were determined in the laboratory.
      Subsequently, participants were administered unpredictable painful and nonpainful
      electrocutaneous shocks (stimulus type), timed to occur either at systole or at
      diastole (cardiac phase) in an event-related design. After each trial,
      participants evaluated their subjective experience. RESULTS: Subjective pain was
      lower for painful stimuli administered at systole compared with diastole, F(1,
      2283) = 4.82, p = 0.03. Individuals with higher baseline BP demonstrated overall
      lower pain perception, F(1, 2164) = 10.47, p < .0001. Within the brain, painful
      stimulation activated somatosensory areas, prefrontal cortex, cingulate cortex,
      posterior insula, amygdala, and the thalamus. Stimuli delivered during systole
      (concurrent with baroreceptor discharge) activated areas associated with
      heightened parasympathetic drive. No stimulus type by cardiac phase interaction
      emerged except for a small cluster located in the right parietal cortex.
      CONCLUSIONS: We confirm the negative associations between BP and pain,
      highlighting the antinociceptive impact of baroreceptor discharge. Neural
      substrates associated with baroreceptor/BP-related hypoalgesia include superior
      parietal lobule, precentral, and lingual gyrus, regions typically involved in the
      cognitive aspects of pain experience.

PMID- 29595709
TI  - Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional
      Reactivity.
AB  - OBJECTIVE: Prediabetes and type 2 diabetes (i.e., hyperglycemia) are
      characterized by insulin resistance. These problems with energy metabolism may
      exacerbate emotional reactivity to negatively valenced stimuli and related
      phenomena such as predisposition toward negative affect, as well as cognitive
      deficits. Higher emotional reactivity is seen with hyperglycemia and insulin
      resistance. However, it is largely unknown how metabolic dysfunction correlates
      with related neural, hormonal, and cognitive outcomes. METHODS: Among 331 adults
      from the Midlife in the United States study, eye-blink response (EBR) we cross
      sectionally examined to gauge reactivity to negative, positive, or neutrally
      valenced pictures from international affect picture system stimuli proximal to an
      acoustic startle probe. Increased EBR to negative stimuli was considered an index
      of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect
      predisposition, was determined using resting electroencephalography. Baseline
      urinary cortisol output was collected. Cognitive performance was gauged using the
      Brief Test of Adult Cognition by telephone. Fasting glucose and insulin
      characterized hyperglycemia or the homeostatic model assessment of insulin
      resistance. RESULTS: Higher homeostatic model assessment of insulin resistance
      corresponded to an increased startle response, measured by EBR magnitude, for
      negative versus positive stimuli (R = 0.218, F(1,457) = 5.48, p = .020,
      euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants
      with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry
      (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD)
      = -.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic
      performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526),
      hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 MUg/12
      hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09,
      p = .025, euglycemia: M(SD) = 1.052 +/- .332, hyperglycemia: M(SD) = .961
      (.362)). CONCLUSIONS: These results suggest that dysmetabolism is associated with
      increased emotional reactivity, predisposition toward negative affect, and
      specific cognitive deficits.

PMID- 29595712
TI  - Financial Disclosure Appendix for "Sientra Shaped and Round Cohesive Gel
      Implants: Long-Term Safety Outcomes".

PMID- 29595710
TI  - Cardiovascular Risk Factors as Differential Predictors of Incident Atypical and
      Typical Major Depressive Disorder in US Adults.
AB  - OBJECTIVE: Although the association between major depressive disorder (MDD) and
      future cardiovascular disease (CVD) is established, less is known about the
      relationship between CVD risk factors and future depression, and no studies have
      examined MDD subtypes. Our objective was to determine whether hypertension,
      tobacco use, and body mass index (BMI) differentially predict atypical and
      typical MDD in a national sample of US adults. METHODS: We examined prospective
      data from 22,915 adults with no depressive disorder history at baseline who
      participated in Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National
      Epidemiologic Survey on Alcohol and Related Conditions. CVD risk factors (Wave 1)
      and incident MDD subtypes (Wave 2) were determined by structured interviews.
      RESULTS: There were 252 patients with atypical MDD and 991 patients with typical
      MDD. In fully adjusted models, baseline hypertension (odds ratio [OR] = 0.57, 95%
      confidence interval [CI] = 0.43-0.76), former tobacco use (OR = 1.46, 95% CI =
      1.20-1.78), and BMI (OR = 1.32, 95% CI = 1.25-1.40; all p < .001) predicted
      incident atypical MDD versus no MDD, whereas no CVD risk factor predicted
      incident typical MDD. Baseline hypertension (OR = 0.52, 95% CI = 0.39-0.70),
      former tobacco use (OR = 1.53, 95% CI = 1.22-1.93), and BMI (OR = 1.26, 95% CI =
      1.18-1.36; all p < .001) also predicted incident atypical MDD versus typical MDD.
      CONCLUSIONS: Our study is the first to report that CVD risk factors
      differentially predict MDD subtypes, with hypertension (protective factor),
      former tobacco use (risk factor), and BMI (risk factor) being stronger predictors
      of incident atypical versus typical MDD. Such evidence could provide insights
      into the etiologies of MDD subtypes and inform interventions tailored to MDD
      subtype.

PMID- 29595711
TI  - Sientra Shaped and Round Cohesive Gel Implants: Long-Term Safety Outcomes.

PMID- 29595713
TI  - Introduction to "Sientra Shaped and Round Cohesive Gel Implants: Long-Term Safety
      Outcomes".

PMID- 29595714
TI  - Ten-year Core Study Data for Sientra's Food and Drug Administration-Approved
      Round and Shaped Breast Implants with Cohesive Silicone Gel.
AB  - BACKGROUND: In March 2012, the United States Food and Drug Administration
      approved Sientra's application for premarket approval of its portfolio of round
      and shaped silicone gel breast implants based on data from the largest silicone
      gel breast implant study to date. This article presents the results of Sientra's
      Core Study at the conclusion of 10 years. METHODS: The Sientra Core Study was a
      10-year, open-label, prospective, multicenter clinical study designed to assess
      the safety and effectiveness of Sientra's breast implants in augmentation and
      reconstruction. A total of 1,788 patients (3,506 implants) were enrolled,
      including 1,116 primary augmentation, 363 revision-augmentation, 225 primary
      reconstruction, and 84 revision-reconstruction. RESULTS: Across all cohorts, the
      rate of rupture by patient was 8.6%, the rate of Baker grade III/IV capsular
      contracture was 13.5%, and the rate of reoperation was 31.5%. The rate of
      capsular contracture was statistically significantly lower for textured devices
      [9.0%; 95% confidence interval (CI), 7.0-11.5%] compared with smooth devices
      (17.5%; 95% CI, 14.9-20.4%). There were no cases of breast implant-associated
      anaplastic large cell lymphoma. Primary reasons for reoperations included
      capsular contracture (18.8%), and style/size change (19.3%), with over 50% of the
      reoperations due to cosmetic reasons. CONCLUSION: The 10-year results of
      Sientra's Core Study support a comprehensive safety and effectiveness profile of
      Sientra's portfolio of round and shaped breast implants.

PMID- 29595715
TI  - Risk Factor Analysis for Capsular Contracture: A 10-Year Sientra Study Using
      Round, Smooth, and Textured Implants for Breast Augmentation.
AB  - BACKGROUND: Despite the increased understanding of surgical best practices,
      capsular contracture remains the most commonly reported complication and reason
      for reoperation following breast implant surgery. This study provides a long-term
      update to a previous investigation of potential contributing risk factors for
      capsular contracture in primary augmentation patients. METHODS: The data used for
      this analysis include 5,122 implants in 2,565 primary augmentation patients
      implanted by 34 surgeons based on long-term results from Sientra's clinical
      study. Potential risk factors, including patient and implant attributes, surgery
      characteristics, pocket irrigation, and postsurgery characteristics, were
      analyzed using frequency and multivariate models. RESULTS: A total of 333
      capsular contracture events in 224 patients were reported. The overall Kaplan
      Meier rate for capsular contracture was 10.8% by device through 10 years. Results
      from the multivariate analysis found 8 factors to be independently associated
      with capsular contracture (implant placement, implant surface, incision site,
      hematoma or seroma development, device size, surgical bra, steroid, and
      antibiotic pocket irrigation; all P values < 0.05). Results from correlation
      analysis found 2 of the 8 factors to be more strongly associated with early onset
      capsular contracture events, compared with those occurring after 2 and 5 years of
      implantation (implant surface and steroid pocket irrigation). CONCLUSION: The
      results of this large-scale, multivariate analysis identified several significant
      risk factors for capsular contracture, including device features (smooth surface,
      smaller size), surgical factors (periareolar incision, subglandular placement,
      antibiotic irrigation), the development of hematoma/seroma, and the use of a
      surgical bra.

PMID- 29595716
TI  - Sientra AlloX2 Short-Term Case Study, Surgical Pearls, and Roundtable Discussion.
AB  - BACKGROUND: The AlloX2 Breast Tissue Expander (Sientra, Santa Barbara, Calif.) is
      a unique device that contains a second port to allow for transdermal
      communication with the pocket around the implant. The injection dome of this
      expander contains two ports; one is used for traditional saline injection, and a
      new second port facilitates fluid drainage from the periprosthetic space through
      an integral drain. The AlloX2 allows for the treatment of seromas and diagnostic
      fluid sampling to identify bacteria and hone antibiotic treatment in the setting
      of periprosthetic infection. This device has a significant advantage over
      traditional expanders, given that seromas and infections are the most common
      complications in implant-based breast reconstruction, with or without the use of
      soft-tissue support matrix. METHODS: This article provides short-term case
      studies and surgical pearls from 3 surgeons who utilize the AlloX2 in primary
      breast reconstruction patients. Three surgeons implanted 40 primary
      reconstruction patients with AlloX2. Follow-up was approximately 6 months, per
      the standard of care. All patients implanted with AlloX2 underwent immediate
      reconstruction, with the exception of 1 delayed reconstruction. RESULTS: The most
      common complications the patients experienced were seromas. In most cases, the
      surgeons successfully used the second port to drain periprosthetic fluid.
      CONCLUSIONS: The AlloX2 has been successful in treating seromas and should be
      considered a tool for noninvasive treatment of common complications of implant
      based breast reconstruction. Three surgeons with varied backgrounds and
      techniques provide their surgical and postoperative management experiences and
      recommendations.

PMID- 29595717
TI  - Results of the Postmarket Clinical Study of the Sientra 207 Highly Cohesive Gel
      Breast Implants in Primary and Revision Augmentation.
AB  - BACKGROUND: Board-certified plastic surgeons utilizing the Sientra 207 Highly
      Cohesive Gel breast implants provided their initial satisfaction with usage and
      postoperative results on primary and revision augmentation patients, and study
      participants provided their satisfaction with surgical result. METHODS: Up to 15
      participating investigators at institutional review board-approved sites enrolled
      up to 180 women who received Sientra 207 implants for primary augmentation or
      revision augmentation procedures. Investigator and participant assessments were
      performed preoperatively and postoperatively at 3, 6, and 12 months. RESULTS: All
      participating surgeons found the implants to be easy or very easy to implant, and
      92 percentage reported satisfaction with surgical results. Patients receiving
      these implants reported similarly high rates of satisfaction (94%). CONCLUSION:
      With this combination of high satisfaction and low complication rates, the
      Sientra 207 silicone breast implants now provide a welcome addition to plastic
      surgeons' breast implant options.

PMID- 29595718
TI  - Breast Cancer following Augmentation Mammaplasty: A Case-Control Study.
AB  - BACKGROUND: The purpose of this study was to determine whether augmentation
      mammaplasty, implant type, and implant location affect breast cancer detection,
      stage, and treatment. METHODS: An institutional case-control study was performed
      of patients with prior breast augmentation undergoing breast cancer treatment
      from 2000 to 2013. Controls were propensity matched and randomized, and data were
      retrospectively reviewed. RESULTS: Forty-eight cases and 302 controls were
      analyzed. Palpable lesions were detected at a smaller size in augmentation
      patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients
      were detected by screening mammography (77.8 percent of cases versus 90.7 percent
      of controls; p = 0.010). Patients with implants were more likely to undergo an
      excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001),
      rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p
      < 0.001). Earlier staging in augmented patients approached but did not reach
      statistical significance (p = 0.073). Augmented patients had higher mastectomy
      rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation
      therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type
      nor anatomic location affected method of diagnosis, stage, or treatment.
      CONCLUSIONS: Palpable detection of breast cancer is more likely at a smaller size
      in augmented patients, yet it is less likely on screening mammography than in
      controls. Augmentation breast cancer patients have a comparable disease stage and
      are more likely to undergo mastectomy rather than lumpectomy. Both silicone and
      saline implants, whether placed submuscularly or subglandularly, have comparable
      effects on breast imaging, biopsy modality, and surgical intervention. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29595719
TI  - Discussion: Enhanced Recovery Pathway in Microvascular Autologous Tissue-Based
      Breast Reconstruction: Should It Become the Standard of Care?

PMID- 29595720
TI  - 5000 Free Flaps and Counting: A 10-Year Review of a Single Academic Institution's
      Microsurgical Development and Outcomes.
AB  - BACKGROUND: The establishment of an effective clinical and academic culture
      within an institution is a multifactorial process. This process is cultivated by
      dynamic elements such as recruitment of an accomplished and diverse faculty,
      patient geographic outreach, clinical outcomes research, and fundamental support
      from all levels of an institution. This study reviews the academic evolution of a
      single academic plastic surgery practice, and summarizes a 10-year experience of
      microsurgical development, clinical outcomes, and academic productivity. METHODS:
      A 10-year retrospective institutional review was performed from fiscal years 2006
      to 2016. Microsurgical flap type and operative volume were measured across all
      microsurgery faculty and participating hospitals. Microvascular compromise and
      flap salvage rates were noted for the six highest volume surgeons. Univariate and
      multivariable predictors of flap salvage were determined. RESULTS: The 5000th
      flap was performed in December of 2015 within this institutional study period.
      Looking at the six highest volume surgeons, free flaps were examined for
      microvascular compromise, with an institutional mean take-back rate of 1.53
      percent and flap loss rate of 0.55 percent across all participating hospitals.
      Overall, 74.4 percent of cases were breast flaps, and the remaining cases were
      extremity and head and neck flaps. CONCLUSIONS: Focused faculty and trainee
      recruitment has resulted in an academically and clinically productive practice.
      Collaboration among faculty, staff, and residents contributes to continual
      learning, innovation, and quality patient care. This established framework,
      constructed based on experience, offers a workable and reproducible model for
      other academic plastic surgery institutions. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 29595721
TI  - Trends in Physician Payments for Breast Reconstruction.
AB  - BACKGROUND: Prosthetic breast reconstruction rates have risen in the United
      States, whereas autologous techniques have stagnated. Meanwhile, single
      institution data demonstrate that physician payments for prosthetic
      reconstruction are rising, while payments for autologous techniques are
      unchanged. This study aims to assess payment trends and variation for tissue
      expander and free flap breast reconstruction. METHODS: The Blue Health
      Intelligence database was queried from 2009 to 2013, identifying women with
      claims for breast reconstruction. Trends in the incidence of surgery and
      physician reimbursement were characterized by method and year using regression
      models. RESULTS: There were 21,259 episodes of breast reconstruction, with a
      significant rise in tissue expander cases (incidence rate ratio, 1.09; p < 0.001)
      and an unchanged incidence of free flap cases (incidence rate ratio, 1.02; p =
      0.222). Bilateral tissue expander cases reimbursed 1.32 times more than
      unilateral tissue expanders, whereas bilateral free flaps reimbursed 1.61 times
      more than unilateral variants. The total growth in adjusted tissue expander mean
      payments was 6.5 percent (from $2232 to $2378) compared with -1.8 percent (from
      $3858 to $3788) for free flaps. Linear modeling showed significant increases for
      tissue expander reimbursements only. Surgeon payments varied more for free flaps
      (the 25th to 75th percentile interquartile range was $2243 for free flaps versus
      $987 for tissue expanders). CONCLUSIONS: The incidence of tissue expander cases
      and reimbursements rose over a period where the incidence of free flap cases and
      reimbursements plateaued. Reasons for stagnation in free flaps are unclear;
      however, the opportunity cost of performing this procedure may incentivize the
      alternative technique. Greater payment variation in autologous reconstruction
      suggests the opportunity for negotiation with payers.

PMID- 29595722
TI  - Comparison of Cartilage-Scoring and Cartilage-Sparing Otoplasty: A Retrospective
      Analysis of Complications and Aesthetic Outcome of 1060 Ears.
AB  - BACKGROUND: Various techniques are used to correct prominent ears. The authors
      describe their experience with four different otoplasty techniques in 565
      patients with congenital deformities of the ears (1060 ears) that were performed
      in their hospital during an 11-year period (2002 to 2012). METHODS: The authors
      divided the techniques into two groups: group I, cartilage-sparing techniques
      (i.e., IA, Mustarde; and IB, Furnas); and group II, cartilage-cutting techniques
      (i.e., IIA, Chongchet; and IIB, concha shell reduction). The authors compared
      early and late and minor and major complications, recurrence rates, and revision
      surgery. Furthermore, aesthetic outcome was scored by three different groups
      (consultant plastic surgeons, plastic surgery residents, and laymen) on a visual
      analogue scale using a blinded random selection of preoperative and postoperative
      photographs. RESULTS: The percentage of complications without the need for
      reoperation was 20 percent and 21 percent in the cartilage-sparing and cartilage
      cutting groups, respectively (p = 0.44). In 6 percent of all cases, a reoperation
      of the otoplasty was required (7 percent and 6 percent in the cartilage-sparing
      and cartilage-cutting groups, respectively). Aesthetic postoperative results
      showed that the cartilage-cutting group scored significantly lower on
      postoperative shape (p = 0.04), result (p = 0.03), and satisfaction (p = 0.04)
      compared with the cartilage-sparing group. CONCLUSIONS: The study shows that
      patients who have undergone operations with cartilage-sparing or cartilage
      cutting techniques have a similar rate of complications and need for reoperation.
      However, the cartilage-sparing techniques have a better aesthetic outcome, as
      judged by the different groups. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 29595723
TI  - Inner Scar Umbilicus: New Horizons for Vertical Abdominoplasty.
AB  - BACKGROUND: It is reasonable that deflated tissue in massive weight loss patients
      may demand not only lifting but also some extent of central body tightening, by
      the fleur-de-lis procedure. Although achieving nice contouring results, poor
      visible scars, including umbilical complications, have restricted the indications
      for the anterior vertical approach. The purpose of this article is to present the
      authors' experience with the inner scar umbilical reconstruction, reflecting
      overall results in vertical abdominoplasties. METHODS: Massive weight loss
      patients who underwent fleur-de-lis abdominoplasties with the inner scar
      umbilicus were reviewed retrospectively. The original stalk was resected along
      with the surgical specimen, and two marked parallel skin flaps were kept and
      sutured against each other into the deep medial fascia, to reconstruct the
      umbilical base. Additional sutures were made to approximate fat tissue
      immediately under and above it, enhancing a deepening effect. Conventional upper
      and lower vertical closure helped to establish the tridimensional shape of the
      new navel. RESULTS: One hundred ten consecutive patients were studied, and 52 (47
      percent) presented small inflammatory exudate arising from the inner suture,
      which resolved with conservative dry dressings. No further umbilical
      complications such as infection, necrosis, dehiscence, widening, or stenosis were
      reported, and all patients showed natural and scarless new navels with nice
      shapes and correct position. CONCLUSIONS: The inner scar umbilicus is a simple,
      safe, and reproducible technique, presenting low complication rates with
      sustainable and natural results. High-quality navel reconstruction favors the
      indication of vertical abdominoplasties, especially for post-bariatric surgery
      body contouring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29595724
TI  - An Update on the Safety and Efficacy of Outpatient Plastic Surgery: A Review of
      26,032 Consecutive Cases.
AB  - BACKGROUND: Outpatient surgery offers many advantages, including cost
      containment, privacy, and convenience. However, patient safety must take
      precedence over these benefits. Limited well-designed studies exist in the
      plastic surgery literature on patient safety in the outpatient setting,
      particularly those that identify risk factors for adverse outcomes. METHODS: A
      retrospective review was performed on 26,032 consecutive cases completed by board
      certified plastic surgeons at an accredited outpatient surgical center between
      1995 and 2017. All cases were reviewed for potential morbidity and mortality
      events, and variables were analyzed to determine potential risk factors for
      postoperative complications and inpatient admission. RESULTS: A total of 26,032
      cases were performed over a 23-year period. There were a total of 203
      complications (0.78 percent). Compared with the control population, the 12
      patients (0.05 percent) that sustained venous thromboembolic events demonstrated
      higher body mass indexes (p < 0.01), greater lipoaspirate amounts (p = 0.04),
      longer operative times (p < 0.01), and were more likely to have undergone a
      combined procedure (p < 0.01). In addition, the 22 patients (0.08 percent) that
      were transferred to inpatient facilities demonstrated greater body mass index (p
      < 0.01) and longer operative times (p = 0.01). CONCLUSIONS: Plastic surgery is
      safe to perform in an accredited outpatient facility for a majority of patients.
      According to the authors' data, postoperative monitoring in a nursing facility
      should be considered for the following high-risk patients: those with a body mass
      index greater than 30 kg/m, operative times greater than 4 hours, lipoaspirate
      volumes greater than 3 liters, and those undergoing combined procedures. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29595725
TI  - Plastic Surgery Complications from Medical Tourism Treated in a U.S. Academic
      Medical Center.
AB  - BACKGROUND: Medical tourism is a growing, multi-billion dollar industry fueled by
      improvements in the global transportation infrastructure. The authors studied
      patients living in the United States who travel to other countries for plastic
      surgical procedures and returned to have their complications treated in the
      authors' center. METHODS: A retrospective patient evaluation was performed.
      Patients who had presented to an urban tertiary academic hospital plastic surgery
      service with complications or complaints associated with plastic surgery
      performed in a developing country were studied. The authors collected demographic
      information, types of surgery performed, destinations, insurance coverage, and
      complications. RESULTS: Seventy-eight patients were identified over 7 years. Most
      commonly, complications were seen following abdominoplasty (n = 35), breast
      augmentation (n = 25), and foreign body injections (n = 15). Eighteen patients
      underwent multiple procedures in one operative setting. The most common
      destination country was the Dominican Republic (n = 59). Complications included
      surgical-site infections (n = 14), pain (n = 14), and wound healing complications
      (n = 12). Eighty-six percent of patients (n = 67) relied on their medical
      insurance to pay for their follow-up care or manage their complications, with the
      most common type of health insurance coverage being Massachusetts Medicaid (n =
      48). CONCLUSIONS: Cosmetic surgery performed in developing countries can carry
      substantial risks of complications that can be challenging to patients, primary
      care providers, insurers, and plastic surgical teams not associated with the
      original surgery. These complications pose significant burdens on our public
      health systems.

PMID- 29595726
TI  - Discussion: Plastic Surgery Complications from Medical Tourism Treated in a U.S.
      Academic Medical Center.

PMID- 29595727
TI  - Discussion: The Boomerang Lift: A Three-Step Compartment-Based Approach to the
      Youthful Cheek.

PMID- 29595728
TI  - Female Cosmetic Genital Surgery.
AB  - Female cosmetic genital surgery is rapidly gaining popularity. Patient demand is
      increasing, and female cosmetic genital surgery is becoming a subspecialty of
      plastic surgery. Two predominant techniques exist in labia minora reduction: edge
      trim and wedge resection. Dr. Hamori prefers the wedge resection for most
      clinical situations. This video vignette clearly describes aesthetic analysis,
      marking, and technical execution for an extended wedge procedure. Patient safety
      and the management of patient expectations are emphasized.

PMID- 29595729
TI  - Discussion: External Volume Expansion Up-Regulates CXCL12 Expression and Enhances
      Mesenchymal Stromal Cell Recruitment toward Expanded Prefabricated Adipose Tissue
      in Rats.

PMID- 29595730
TI  - Recovery of Elbow Flexion after Nerve Reconstruction versus Free Functional
      Muscle Transfer for Late, Traumatic Brachial Plexus Palsy: A Systematic Review.
AB  - BACKGROUND: In late presentation of brachial plexus trauma, it is unclear whether
      donor nerves should be devoted to nerve reconstruction or reserved for free
      functional muscle transfer. The authors systematically reviewed recovery of elbow
      flexion after nerve reconstruction versus free functional muscle transfer for
      late, traumatic brachial plexus palsy. METHODS: A systematic review was performed
      using the PubMed, Embase, and Cochrane databases to identify all cases of
      traumatic brachial plexus palsy in patients aged 18 years or older. Patients who
      underwent late (>=12 months) nerve reconstruction or free functional muscle
      transfer for elbow flexion were included. Age, time to operation, and level of
      brachial plexus injury were recorded. British Medical Research Council grade for
      strength and range of motion were evaluated for elbow flexion. RESULTS: Thirty
      three studies met criteria, for a total of 103 patients (nerve reconstruction, n
      = 53; free functional muscle transfer, n = 50). There were no differences across
      groups regarding surgical age (time from injury) and preoperative elbow flexion.
      For upper trunk injuries, 53 percent of reconstruction patients versus 100
      percent of muscle transfer patients achieved grade M3 or greater strength, and 43
      percent of reconstruction patients versus 70 percent of muscle transfer patients
      achieved grade M4 or greater strength. Of the total brachial plexus injuries, 37
      percent of reconstruction patients versus 78 percent of muscle transfer patients
      achieved grade M3 or greater strength, and 16 percent of reconstruction patients
      versus 46 percent of muscle transfer patients achieved grades M4 or greater
      strength. CONCLUSION: In late presentation of traumatic brachial plexus injuries,
      donor nerves should be reserved for free functional muscle transfer to restore
      elbow flexion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29595731
TI  - Augmentation of the Median Tubercle with Dermis-Fat Graft in Children with
      Repaired Cleft Lip.
AB  - BACKGROUND: Deficiency of the median tubercle is a common residual deformity
      after repair of cleft lip. The purpose of this study was to analyze the change in
      labial contour after insertion of a dermis-fat graft. METHODS: Patients with
      repaired cleft lip who underwent secondary dermis-fat grafting of the median
      tubercle between 2012 and 2015, along with preoperative and greater than or equal
      to 3-month postoperative three-dimensional photographs, were included. The
      photographs were registered to one another and measurements made before and after
      grafting using anthropometric landmarks. Outcome variables included the
      following: labial surface area, midline labial height (ls-sto), and lateral
      labial height (cphi-sto'). RESULTS: Twenty-five patients were included: 14 with
      unilateral and 11 with bilateral repaired cleft lip. Mean age at graft placement
      was 10.9 +/- 3.2 years. Preoperative and postoperative three-dimensional images
      were taken at 13.6 +/- 21.6 weeks before and 34.8 +/- 25.1 weeks after the
      procedure, respectively. There were significant increases in labial surface area
      (11.5 percent; p = 0.019) and labial height (14.1 to 18.5 percent; p = 0.002)
      after grafting. Augmentation was greater in bilateral clefts (25.5 percent at
      midline and 16.8 percent laterally) compared with unilateral clefts (11.6 percent
      at midline and 12.5 percent on the grafted noncleft side). Intrarater and
      interrater reliability was excellent for all measurements. CONCLUSION: Dermis-fat
      grafting significantly increases contour of the median tubercle in patients with
      repaired cleft lip. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29595732
TI  - Outcome of Palate Re-repair with Radical Repositioning of the Levator Muscle
      Sling as a First-Line Strategy in Postpalatoplasty Velopharyngeal Incompetence
      Management Protocol.
AB  - BACKGROUND: Palatal re-repair aims to improve velar function by retropositioning
      the levator muscles. Although it has become a popular procedure, very few studies
      document its efficacy. To date, this is the largest series reported to clarify
      its indications and efficacy. METHODS: One hundred eighty-three consecutive cleft
      patients presenting with velopharyngeal incompetence and evidence of abnormally
      oriented levator muscles underwent palate re-repair (regardless of the gap size)
      performed by a single surgeon from 2000 to 2015. Perceptual speech assessment was
      performed using the Pittsburgh Weighted Speech Score. Other patients' demographic
      data were collected. RESULTS: Complete records of 111 patients were available.
      Eighteen cases were syndromic (18.9 percent). Postoperatively, there was highly
      significant improvement (p < 0.001) in nasal emission (from 2.24 to 0.64),
      nasality (from 3.44 to 1.27), articulation (from 5.32 to 2.01), and total score
      (from 11.29 to 4.11). Speech became normal/borderline normal, improved or did not
      improve in 66.7, 24.3, and 9 percent of patients, respectively. An initial
      diagnosis of isolated cleft palate, Caucasians, intravelar veloplasty in the
      primary repair, older patients, and nonsyndromic cases were associated with
      better outcome. There were no reported cases of postoperative fistula or new
      obstructive sleep apnea. CONCLUSIONS: This large series study provides
      confirmatory evidence of the effectiveness and safety of the re-repair procedure.
      It is recommended as a first-line procedure in all velopharyngeal incompetence
      cases with abnormally oriented levator muscles regardless of gap size, even if
      the primary operation included prior muscle dissection. The pharyngoplasty rate
      could be significantly reduced with the current protocol. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 29595733
TI  - Predictors for Unfavorable Projection of the Constructed Auricle following Ear
      Elevation Surgery in Microtia Reconstruction.
AB  - BACKGROUND: Nagata's two-stage technique for microtia reconstruction using
      autologous costal cartilage consists of the implantation of a fabricated
      cartilage framework and the elevation of the constructed auricle. Achieving long
      lasting, sufficient projection of the auricle is a goal of second-stage surgery;
      however, unfavorable outcomes have been seen in some patients, with suboptimal
      long-term elevation. The present study aimed to investigate prognostic factors
      that might contribute to adverse outcomes following the ear elevation operation.
      METHODS: Outcomes of patients with congenital microtia who underwent auricular
      reconstruction with a modified Nagata technique between January of 2007 and June
      of 2015 were reviewed. Unfavorable elevation was defined as cases with an
      auriculocephalic angle less than 20 degrees or with a shallow auricular sulcus
      requiring revision operations. Univariate and multivariate analyses were
      conducted to identify independent predictors for the unfavorable elevation.
      RESULTS: A total of 309 patients representing 323 cases were analyzed with a
      median follow-up period of 26 months. The mean age of the patients was 15.1
      years. The majority of cases had lobule-type microtia. Hemifacial microsomia was
      present in 114 cases. Canalplasty was performed in 117 cases before the auricular
      elevation. Unfavorable elevation was observed in 72 cases (22.3 percent).
      Multivariate analyses showed that the presence of hemifacial microsomia and
      performance of canalplasty less than or equal to 12 months before the ear
      elevation operation were independent risk factors for the unfavorable elevation.
      CONCLUSION: Several preoperative factors, including combined anomalies and
      operative timing and sequences, might influence the outcomes of the ear elevation
      operation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29595734
TI  - Incidence of Cranial Base Suture Fusion in Infants with Craniosynostosis.
AB  - BACKGROUND: Cranial base sutures are important drivers of both facial and cranial
      growth. The purpose of this study was to compare the incidence and location of
      cranial base suture fusion among three groups: nonaffected controls, patients
      with nonsyndromic craniosynostosis, and patients with syndromic craniosynostosis.
      METHODS: Patients and computed tomographic scans were accrued from the authors'
      prospective craniofacial database. Computed tomographic scans were graded on the
      frequency of cranial vault and cranial base suture/synchondrosis fusion (0, open;
      1, partially/completely fused) by an attending craniofacial surgeon and
      neuroradiologist. Statistical comparisons were conducted on location and rates of
      fusion, age, and diagnosis. RESULTS: One hundred forty patients met inclusion
      criteria: 55 syndromic, 64 nonsyndromic, and 21 controls. Average age at computed
      tomography of syndromic patients (3.6 +/- 3.1 months) was younger than that of
      nonsyndromic patients (5.4 +/- 3.1 months; p = 0.001) and control subjects (5.1
      +/- 3.2 months; p = 0.058). Syndromic craniosynostotic patients had over three
      times as many cranial base minor sutures fused (2.2 +/- 2.5) as nonsyndromic
      craniosynostosis patients (0.7 +/- 1.2; p < 0.001) and controls (0.4 +/- 0.8; p =
      0.002), whose rates of fusion were statistically equivalent (p = 0.342).
      Syndromic craniosynostosis patients had a greater frequency of cranial base
      suture fusion in the coronal branches, squamosal arch, and posterior
      intraoccipital synchondrosis (p < 0.05). CONCLUSIONS: Patients with syndromic
      craniosynostosis have higher rates of cranial base suture fusion in infancy,
      especially in the coronal arches, and this may have significant implications for
      both cranial and facial growth. In contrast, patients with nonsyndromic
      craniosynostosis have similar rates and sites of cranial base suture fusion as
      controls. Interestingly, there is a low, "normal," rate of cranial base
      suture/synchondrosis closure in infancy, the implications of which are unknown.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29595735
TI  - A New Composite Eyeball-Periorbital Transplantation Model in Humans: An
      Anatomical Study in Preparation for Eyeball Transplantation.
AB  - BACKGROUND: Vascularized composite allotransplantation offers a new hope for
      restoration of orbital content and perhaps vision. The aim of this study was to
      introduce a new composite eyeball-periorbital transplantation model in fresh
      cadavers in preparation for composite eyeball allotransplantation in humans.
      METHODS: The composite eyeball-periorbital transplantation flap borders included
      the inferior border, outlined by the infraorbital rim; the medial border, created
      by the nasal dorsum; the lateral border, created by the lateral orbital rim; and
      the superior border, created by the superior part of the eyebrow. The pedicle of
      the flap included the facial artery, superficial temporal artery, and external
      jugular vein. The skin and subcutaneous tissues of the periorbital region were
      dissected and the bony tissue was reached. A coronal incision was performed and
      the frontal lobe of the brain was reached by means of frontal osteotomy.
      Ophthalmic and oculomotor nerves were also included in the flap. After a "box
      osteotomy" around the orbit, the dissection was completed. Methylene blue and
      indocyanine green injection (SPY Elite System) was performed to show the
      integrity of the vascular territories after facial flap harvest. RESULTS:
      Adequate venous return was observed within the flap after methylene blue dye
      injection. Laser-assisted indocyanine green angiography identified a well-defined
      vascular network within the entire composite eyeball-periorbital transplantation
      flap. CONCLUSIONS: For the first time, a novel composite eyeball-periorbital
      transplantation model in human cadavers was introduced. Good perfusion of the
      flap confirmed the feasibility of composite eyeball-periorbital transplantation
      in the clinical setting. Although harvesting of the flap is challenging, it
      introduces a new option for reconstruction of the periorbital region including
      the eyeball.

PMID- 29595736
TI  - Cranial Nerve Coactivation and Implication for Nerve Transfers to the Facial
      Nerve.
AB  - In reanimation surgery, effortless smile can be achieved by a nonfacial donor
      nerve. The underlying mechanisms for this smile development, and which is the
      best nonfacial neurotizer, need further clarification. The aim of the present
      study was therefore to further explore the natural coactivation between facial
      mimic muscles and muscles innervated by the most common donor nerves used in
      smile reanimation. The study was conducted in 10 healthy adults. Correlation
      between voluntary facial muscle movements and simultaneous electromyographic
      activity in muscles innervated by the masseter, hypoglossal, and spinal accessory
      nerves was assessed. The association between voluntary movements in the latter
      muscles and simultaneous electromyographic activity in facial muscles was also
      studied. Smile coactivated the masseter and tongue muscles equally. During the
      seven mimic movements, the masseter muscle had fewer electromyographically
      measured coactivations compared with the tongue (two of seven versus five of
      seven). The trapezius muscle demonstrated no coactivation during mimic movements.
      Movements of the masseter, tongue, and trapezius muscles induced
      electromyographically recorded coactivation in the facial muscles. Bite resulted
      in the strongest coactivation of the zygomaticus major muscle. The authors
      demonstrated coactivation between voluntary smile and the masseter and tongue
      muscles. During voluntary bite, strong coactivation of the zygomaticus major
      muscle was noted. The narrower coactivation pattern in the masseter muscle may be
      advantageous for central relearning and the development of a spontaneous smile.
      The strong coactivation between the masseter muscle and the zygomaticus major
      indicates that the masseter nerve may be preferred in smile reanimation.

PMID- 29595737
TI  - Surgical Approach to Injuries of the Cervical Plexus and Its Peripheral Nerve
      Branches.
AB  - BACKGROUND: Located in the neck beneath the sternocleidomastoid muscle, the
      cervical plexus comprises a coalition of nerves originating from C1 through C4,
      which provide input to four cutaneous, seven motor, and three cranial nerves and
      the sympathetic trunk. Sporadic instances of injury to these superficial nerves
      have been reported. Nevertheless, this specific anatomical cause of neurogenic
      pain remains incompletely described and underrecognized. METHODS: Twelve patients
      presented with pain and were diagnosed with various combinations of injury to the
      lesser occipital, great auricular, transverse cervical, and supraclavicular
      nerves. Inciting events included prior face lift, migraine, and thoracic outlet
      procedures; and traumatic events including seatbelt trauma, a fall, and a
      clavicular fracture. History and examination suggested injury to the cervical
      plexus, and nerve blocks confirmed the diagnoses. Neurectomy with intramuscular
      transposition was performed for three nerve branches in one patient, two branches
      in two patients, and one branch in the remaining nine patients. RESULTS: Nine of
      the twelve patients had complete relief of their cervical plexus-related pain.
      The three failures were in patients with pain after previous face-lift surgery.
      Residual perception of neck tightness and choking sensation persisted despite
      relief of cheek and ear pain. CONCLUSIONS: Knowledge of the cervical plexus
      anatomy and its branches is crucial for surgeons operating in this area to
      minimize iatrogenic nerve injury. In addition, neuromas should be considered a
      likely cause of pain and dysesthesia following surgery or injury. Proper
      diagnosis and surgical intervention can have a significantly positive effect on
      these debilitating problems. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29595738
TI  - Patient-Reported Outcome Measures Used in Gender Confirmation Surgery: A
      Systematic Review.
AB  - BACKGROUND: The usefulness of patient-reported outcome measures is emphasized
      along with the development of patient-centered care. When implementing patient
      reported outcome measures, evidence of the instrument's validity, reliability,
      and responsiveness in the target population is necessary to secure accurate
      reporting of the patient's experience. The aim of this study was to identify the
      literature in which structured patient-reported outcome measures have been used
      to evaluate the results of gender confirmation surgery, and to systematically
      evaluate the validity of these instruments. METHODS: A systematic review of the
      current literature was performed to identify structured patient-reported outcome
      measures used to evaluate the outcome of gender confirmation surgery. The
      identified instruments' validity in the transgender population was assessed for
      adherence to international guidelines for development and validation of health
      outcomes instruments. RESULTS: A total of 110 instruments were identified: 64 ad
      hoc; six generic; 24 evaluating psychiatric, social, or psychosocial aspects;
      nine evaluating function but only valid in other patient groups; five ad hoc with
      some formal development/validation; and two specific for gender dysphoria.
      CONCLUSIONS: There is a lack of patient-reported outcome measures that are valid
      for the transgender population and concurrently sensitive enough to evaluate
      gender confirmation surgery without the influence of other gender confirming
      interventions. Basing research on instruments without confirmed validity
      decreases the validity of the study itself; thus, previous research using patient
      reported outcome measures to evaluate gender confirmation surgery can be
      considered to have a low level of evidence. To obtain valid patient-reported
      outcome measures, specific for evaluating the results of gender confirmation
      surgery, development of new instruments or adaptation of existing instruments is
      needed.

PMID- 29595739
TI  - How to Diagnose and Treat Breast Implant-Associated Anaplastic Large Cell
      Lymphoma.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe the diagnostic criteria for breast implant-associated (BIA)
      anaplastic large cell lymphoma (ALCL). 2. Appropriately evaluate a patient with
      suspected BIA-ALCL, including appropriate imaging, laboratory tests, and
      pathologic evaluation. 3. Understand the operative treatment of BIA-ALCL, and
      indications for systemic chemotherapy and/or radiation therapy in advanced
      disease. 4. Understand treatment outcomes and prognosis based on stage of
      disease. SUMMARY: The goal of this continuing medical education module is to
      present the assessment of a patient with suspected breast implant-associated
      anaplastic large cell lymphoma, the evaluation and diagnosis, the preoperative
      oncologic workup, the formation and execution of a surgical treatment plan, and
      the inclusion of adjunct treatments when indicated. In addition, staging and
      disease progression for treatment of breast implant-associated anaplastic large
      cell lymphoma are discussed.

PMID- 29595740
TI  - Why Videos Matter So Much in Plastic Surgery Today: A Complete Index of Videos in
      Plastic and Reconstructive Surgery and Plastic and Reconstructive Surgery Global
      Open.
AB  - The main purpose of this article is to provide the reader with an easily
      searchable online index of the first 1976 videos published in Plastic and
      Reconstructive Surgery and Plastic and Reconstructive Surgery Global Open to
      facilitate access to readers. The authors also describe the history and evolution
      of video articles in the first journal to provide a large offline video library
      of plastic surgery. The importance of videos in plastic surgery education is
      explored.

PMID- 29595741
TI  - Learning from an Unsuccessful Study Idea: Reflection and Application of
      Innovative Techniques to Prevent Future Failures.
AB  - A well-organized, thoughtful study design is essential for creating an impactful
      study. However, pressures promoting high output from researchers can lead to
      rushed study proposals that overlook critical weaknesses in the study design that
      can affect the validity of the conclusions. Researchers can benefit from thorough
      review of past failed proposals when crafting new research ideas. Conceptual
      frameworks and root cause analysis are two innovative techniques that can be used
      during study development to identify flaws and prevent study failures. In
      addition, conceptual frameworks and root cause analysis can be combined to
      complement each other to provide both a big picture and detailed view of a study
      proposal. This article describes these two common analytical methods and provides
      an example of how they can be used to evaluate and improve a study design by
      critically examining a previous failed research idea.

PMID- 29595742
TI  - Factors Affecting Women's Success in Academic and Private Practice Plastic
      Surgery.
AB  - Because plastic surgery trainees generally spend the majority of their training
      in academic centers and may have minimal exposure to other practice models, it
      can be difficult to decide which is the best route to achieve satisfaction and
      success. Surgeons need to be aware of benefits and challenges associated with
      different practice models and with workplace factors in general that contribute
      to happiness at work. This article reviews common practice models and provide
      specific and practical advice for the female surgeon.

PMID- 29595743
TI  - The Divergence of Ethics and Professionalism in the Social Media Arena.

PMID- 29595744
TI  - High-Resolution Magnetic Resonance Imaging of Aging Upper Face Fat Compartments:
      Correction.

PMID- 29595745
TI  - Direct-to-Implant Breast Reconstruction in Women Older than 65 Years: A
      Retrospective Analysis of Complication Rate and Overall Outcomes: Correction.

PMID- 29595746
TI  - Vectra 3D Imaging for Quantitative Volumetric Analysis of the Upper Limb: A
      Feasibility Study for Tracking Outcomes of Lymphedema Treatment.

PMID- 29595747
TI  - Postoperative Infection in Patients Undergoing Posterior Lumbosacral Spinal
      Surgery: A Pictorial Guide for Diagnosis and Early Treatment.
AB  - Surgical site infections after posterior spinal surgery may lead to
      spondylodiscitis, pseudarthrosis, correction loss, adverse neurological sequelae,
      sepsis, and poor outcomes if not treated immediately. Infection rates vary
      depending on the type and extent of operative procedures, use of instrumentation,
      and patients' risk factors. Image evaluation is crucial for early diagnosis and
      should be complementary to clinical routes, laboratory survey, and treatment
      timing. Magnetic resonance imaging detects early inflammatory infiltration into
      the vertebrae and soft tissues, including hyperemic changes of edematous marrow,
      vertebral endplate, and abscess or phlegmon accumulation around the
      intervertebral disk, epidural, and paravertebral spaces. Aggressive surgical
      treatment can eradicate infection sources, obtain a stable wound closure,
      decrease morbidity, and restore spinal integrity. Organ/space infection is
      defined as any body parts opened to manipulate other than superficial/deep
      incision. Advanced magnetic resonance imaging evaluating abnormal fluid
      accumulation, heterogenous contrast enhancement of the endplate erosion due to
      cage/screw infection is categorized to inform a presumptive diagnosis for early
      implant salvage. However, patients' defense response, infection severity,
      bacteriology, treatment timing, spinal stability, and available medical and
      surgical options must be fully considered. Revision surgery is indicated for
      pseudarthrosis, implant loosening with correction loss, recalcitrant
      spondylodiscitis, and adjacent segment diseases for infection control.

PMID- 29595748
TI  - Is it Safe to Use Synthetic Grafts in Pyogenic Vertebral Osteodiskitis When
      Surgical Debridement is Required?

PMID- 29595750
TI  - Cantu syndrome, the changing phenotype: a report of the two oldest Dutch
      patients.

PMID- 29595749
TI  - A novel in-frame deletion in ZMPSTE24 is associated with autosomal recessive
      acrogeria (Gottron type) in an extended consanguineous family.

PMID- 29595752
TI  - Reply to the Letter to the Editor: No Difference Between Trabecular Metal Cones
      and Femoral Head Allografts in Revision TKA: Minimum 5-year Followup.

PMID- 29595751
TI  - How does information on the harms and benefits of cervical cancer screening alter
      the intention to be screened?: a randomized survey of Norwegian women.
AB  - Cervical cancer (CC) is the 13th most frequent cancer among women in Norway, but
      the third most common among women aged 25-49 years. The national screening
      program sends information letters to promote screening participation. We aimed to
      evaluate how women's stated intention to participate in screening and pursue
      treatment changed with the provision of additional information on harms
      associated with screening, and to assess women's preferences on the timing and
      source of such information. We administered a web-based questionnaire to a panel
      of Norwegian women aged 25-69 years and randomized into three groups on the basis
      of when in the screening process additional information was introduced: (i)
      invited for routine screening, (ii) recommended an additional test following
      detection of cellular abnormalities, and (iii) recommended precancer treatment. A
      fourth (control) group did not receive any additional information. Results show
      that among 1060 respondents, additional information did not significantly alter
      women's stated intentions to screen. However, it created decision uncertainty on
      when treatment was recommended (8.76-9.09 vs. 9.40; 10-point Likert scale;
      P=0.004). Over 80% of women favored receiving information on harms and 59%
      preferred that information come from a qualified public health authority. Nearly
      90% of women in all groups overestimated women's lifetime risk of CC. In
      conclusion, additional information on harms did not alter Norwegian women's
      stated intention to screen for CC; yet, it resulted in greater decision
      uncertainty to undergo precancer treatment. Incorporating information on harms
      into invitation letters is warranted as it would increase women's ability to make
      informed choices.

PMID- 29595753
TI  - Dose Efficiency of Quarter-Millimeter Photon-Counting Computed Tomography: First
      in-Human Results.
AB  - PURPOSE: The aim of this study was to assess the clinical feasibility, image
      quality, and radiation dose implications of 0.25-mm imaging mode in a cohort of
      humans, achieved by dividing the photon-counting detector (PCD) size in half
      compared with standard-resolution photon-counting computed tomography (CT) (0.5
      mm). METHODS: In this technical feasibility study, a whole-body prototype PCD-CT
      scanner was studied in the 0.25 mm detector mode (measured at isocenter). A high
      resolution PCD-CT protocol was first tested in phantom and canine studies in
      terms of image noise and spatial resolution. Then, 8 human subjects (mean age, 58
      +/- 8 years; 2 men) underwent axial PCD 0.25-mm scans of the brain, the thorax,
      and at the level of the upper left kidney. Filtered backprojection reconstruction
      was performed with a sharp kernel (B70) for standard-resolution and high
      resolution data at 0.5-mm isotropic image voxel. High-resolution data, in
      addition, were reconstructed with an ultrasharp kernel (U70) at 0.25-mm isotropic
      voxels. RESULTS: Image reconstructions from the PCD 0.25-mm detector system led
      to an improvement in resolution from 9 to 18 line pairs/cm in a line pair
      phantom. Modulation transfer function improved from 9.5 to 15.8 line pairs/cm at
      10% modulation transfer function. When fully exploiting this improvement, image
      noise increased by 75% compared with dose-matched 0.5-mm slice PCD standard
      resolution acquisition. However, when comparing with standard-resolution data at
      same in-plane resolution and slice thickness, the PCD 0.25-mm detector mode
      showed 19% less image noise in phantom, animal, and human scans. CONCLUSION: High
      resolution photon-counting CT in humans showed improved image quality in terms of
      spatial resolution and image noise compared with standard-resolution photon
      counting.

PMID- 29595754
TI  - The Importance and Quantification of Plutonium Binding in Human Lungs.
AB  - Epidemiological studies have shown that the main risk arising from exposure to
      plutonium aerosols is lung cancer, with other detrimental effects in the bone and
      liver. A realistic assessment of these risks, in turn, depends on the accuracy of
      the dosimetric models used to calculate doses in such studies. A state-of-the-art
      biokinetic model for plutonium, based on the current International Commission on
      Radiological Protection biokinetic model, has been developed for this purpose in
      an epidemiological study involving the plutonium exposure of Mayak workers in
      Ozersk, Russia. One important consequence of this model is that the lung dose is
      extremely sensitive to the fraction (fb) of plutonium, which becomes bound to
      lung tissue after it dissolves. It has been shown that if just 1% of the material
      becomes bound in the bronchial region, this will double the lung dose.
      Furthermore, fb is very difficult to quantify from experimental measurements.
      This paper summarizes the work carried out thus far to quantify fb. Bayesian
      techniques have been used to analyze data from different sources, including both
      humans and dogs, and the results suggest a small, but nonzero, fraction of < 1%.
      A Bayesian analysis of 20 Mayak workers exposed to plutonium nitrate suggests an
      fb between 0 and 0.3%. Based on this work, the International Commission on
      Radiological Protection is currently considering the adoption of a value of 0.2%
      for the default bound fraction for all actinides in its forthcoming
      recommendations on internal dosimetry. In an attempt to corroborate these
      findings, further experimental work has been carried out by the United States
      Transuranium and Uranium Registries. This work has involved direct measurements
      of plutonium in the respiratory tract tissues of workers who have been exposed to
      soluble plutonium nitrate. Without binding, one would not expect to see any
      activity remaining in the lungs at long times after exposure since it would have
      been cleared by the natural process of mucociliary clearance. Further supportive
      study of workers exposed to plutonium oxide is planned. This paper ascertains the
      extent to which these results corroborate previous inferences concerning the
      bound fraction.

PMID- 29595755
TI  - The Pseudo-Pelger huet Cell as a Retrospective Dosimeter: Analysis of a Radium
      Dial Painter Cohort.
AB  - Recently, the pseudo-Pelger Huet anomaly in peripheral blood neutrophils has been
      described as a new radiation-induced, stable biomarker. In this study, pseudo
      Pelger Huet anomaly was examined in peripheral blood slides from a cohort of 166
      former radium dial painters and ancillary personnel in the radium dial industry,
      35 of whom had a marrow dose of zero above background. Members of the radium dial
      painter cohort ingested Ra and Ra at an early age (average age 20.6 +/- 5.4 y;
      range 13-40 y) during the years 1914-1955. Exposure duration ranged from 1-1,820
      wk with marrow dose 1.5-6,750 mGy. Pseudo-Pelger Huet anomaly expressed as a
      percentage of total neutrophils in this cohort rises in a sigmoidal fashion over
      five decades of red marrow dose. Six subjects in this cohort eventually developed
      malignancies: five osteosarcomas and one mastoid cell neoplasm. The pseudo-Pelger
      Huet anomaly percentage in these cases of neoplasm increases with marrow dose and
      is best fit with a sigmoid function, suggestive of a threshold effect. No
      sarcomas are seen for a marrow dose under 2 Gy. These results indicate that
      pseudo-Pelger Huet anomaly in peripheral blood is a reasonable surrogate for the
      estimation of alpha dose to bone marrow in historic radiation cases. Hypotheses
      are discussed to explain late (months to years), early (hours to days), and
      intermediate (weeks to months) effects of ionizing radiation, respectively, on
      the expression of genes encoding inner nuclear membrane proteins and their
      receptors, on the structure and function of nuclear membrane proteins and lipids,
      and on cytokinesis through chromatin bridge formation.

PMID- 29595757
TI  - Prognosis and outcome in CDH1-mutant lobular breast cancer.

PMID- 29595756
TI  - Tobacco smoking and gastric cancer: meta-analyses of published data versus pooled
      analyses of individual participant data (StoP Project).
AB  - Tobacco smoking is one of the main risk factors for gastric cancer, but the
      magnitude of the association estimated by conventional systematic reviews and
      meta-analyses might be inaccurate, due to heterogeneous reporting of data and
      publication bias. We aimed to quantify the combined impact of publication-related
      biases, and heterogeneity in data analysis or presentation, in the summary
      estimates obtained from conventional meta-analyses. We compared results from
      individual participant data pooled-analyses, including the studies in the Stomach
      Cancer Pooling (StoP) Project, with conventional meta-analyses carried out using
      only data available in previously published reports from the same studies. From
      the 23 studies in the StoP Project, 20 had published reports with information on
      smoking and gastric cancer, but only six had specific data for gastric cardia
      cancer and seven had data on the daily number of cigarettes smoked. Compared to
      the results obtained with the StoP database, conventional meta-analyses
      overvalued the relation between ever smoking (summary odds ratios ranging from 7%
      higher for all studies to 22% higher for the risk of gastric cardia cancer) and
      yielded less precise summary estimates (SE <=2.4 times higher). Additionally,
      funnel plot asymmetry and corresponding hypotheses tests were suggestive of
      publication bias. Conventional meta-analyses and individual participant data
      pooled-analyses reached similar conclusions on the direction of the association
      between smoking and gastric cancer. However, published data tended to
      overestimate the magnitude of the effects, possibly due to publication biases and
      limited the analyses by different levels of exposure or cancer subtypes.

PMID- 29595758
TI  - Surgical Treatment of Early-Stage Cervical Cancer: A Multi-Institution Experience
      in 2124 Cases in The Netherlands Over a 30-Year Period.
AB  - OBJECTIVE: This study aimed to describe the pattern of recurrence and survival
      related to prognostic variables, including type of surgery as a clinical
      variable, in patients surgically treated for early cervix cancer. METHODS:
      Records of 2124 patients who underwent a radical hysterectomy for International
      Federation of Gynaecology and Obstetrics stage I/IIA cervical cancer between 1982
      and 2011 were reviewed. Clinical-pathologic prognostic variables, also including
      extent of parametrectomy, were identified and used in a multivariable Cox
      proportional hazard model to explore associations between disease-free survival
      (DFS) and prognostic variables. RESULTS: The 5-year DFS for the total group was
      86%. Large tumor diameter, nonsquamous histology, lymph node metastases,
      parametrial involvement, lymph vascular space invasion, deep stromal invasion,
      and less radical surgery were independent poor prognostic variables for survival.
      Disease-free survival was independently associated with the type of radical
      hysterectomy with pelvic lymphadenectomy in favor of more radical parametrectomy
      (hazard ratio, 2.0; 95% confidence interval, 1.6-2.5). This difference was not
      found in tumors with a diameter of at least 20 mm. CONCLUSIONS: This study
      confirms that variables such as large tumor diameter, nonsquamous histology,
      lymph vascular space invasion, deep stromal invasion, positive lymph nodes, and
      parametrial infiltration are poor prognostic variables in early cervix cancer
      treated by surgery. The extent of parametrectomy had no influence on survival in
      tumors of 20 mm or less. For larger tumors, a more radical hysterectomy might be
      associated with better DFS. Taking into account the possible bias in this study
      as a result of its retrospective design, ideally a prospective cohort study with
      clear definition of radicality is necessary to answer this important clinical
      question.

PMID- 29595759
TI  - Multimodal Management of Locally Advanced Neuroendocrine Cervical Carcinoma: A
      Single Institution Experience.
AB  - OBJECTIVE: The aim of this study was to report our institutional experience of a
      multimodal approach for treatment of locally advanced high-grade neuroendocrine
      cervical cancer. METHODS AND MATERIALS: Patients with primary locally advanced
      neuroendocrine cervical cancer diagnosed between 2001 and 2014 were included. The
      scheduled treatment sequence was as follows: pelvic +/- para-aortic radiotherapy
      (according to tumor stage), associated with chemotherapy based on platine
      derivate and etoposide regimen, followed with a brachytherapy boost, then
      completion surgery if there was no progression +/- consolidation etoposide
      chemotherapy (for a total of 5-6 cycles). Disease-free survival (DFS) and overall
      survival (OS) were reported and prognostic factors were searched. RESULTS: A
      total of 24 patients fulfilled inclusion criteria. Median age was 48 (range 22-77
      years). Fourteen patients (58%) had pelvic lymph node metastases. After
      chemoradiation/brachytherapy, a radical hysterectomy could be performed in 18 of
      24 patients (75%). Histologically complete resection was achieved in 14 (78%) of
      18 patients. Complete pathological response was reported in 7 (39%) of 18. With
      median follow-up of 29.7 months, 10 (42%) of 24 patients experienced tumor
      relapse, all associated with distant failure, including one local failure. The
      DFS and OS rates estimated at 3 years were 55% and 63%, respectively. Lymph node
      metastases and tumor stage were prognostic for DFS (P = 0.016 and P = 0.022,
      respectively). Complete resection was associated with a lower incidence of
      relapses, as compared with microscopically incomplete resection (P = 0.04). A
      total of 12 (86%) of 14 patients with histologically complete resection were in
      complete remission at last follow-up. Apart from manageable acute hematological
      toxicities, most treatment complications were mild to moderate. CONCLUSIONS: This
      series based on a multimodal management compares favorably with previously
      published data. Most patients could be eligible to surgery, and complete
      remission was achieved in 85% of those amenable to complete resection.

PMID- 29595760
TI  - Intestinal Surgery in Gynecologic Oncology: Are We Training for the Future?
AB  - OBJECTIVE: The objective of this study was to assess the scope of intestinal
      surgery training across gynecologic oncology fellowships in the United States and
      identify factors associated with perceived preparedness to perform intestinal
      surgery independently. MATERIALS/METHODS: An institutional review board-approved
      survey was distributed to Society of Gynecologic Oncology fellows and candidate
      members within the first 3 years of practice. Questions addressed demographics,
      operative experience, preparedness and plans for performing intestinal surgery,
      and attitudes toward gynecologic oncologists (GOs) performing intestinal surgery.
      Responses were analyzed using descriptive statistics as well as univariate and
      multivariate analyses. RESULTS: Of 374 Society of Gynecologic Oncology members
      invited, 108 (29%) responded, including 38 fellows (35%) and 53 recent graduates
      (49%). Fifteen (14%) reported more than 3 years of practice and were excluded.
      Most participants (96%) received intestinal surgery training from GOs, and 64%
      reported that all faculty routinely performed intestinal surgery. Most
      participants (81%) believed GOs should perform intestinal procedures, whereas
      only 58% felt prepared and 59% planned to perform intestinal procedures
      independently. Fellows who performed more than 10 intestinal diversion
      procedures, participated directed in intestine-related intraoperative
      consultations, or reported that all faculty performed intestinal surgery were
      more likely to feel prepared to perform intestinal surgery independently. Sex,
      training region, intended practice environment, and fellowship curriculum were
      not associated with preparedness to perform intestinal surgery. CONCLUSIONS:
      Almost half of gynecologic oncology fellows and recent graduates in the United
      States do not feel prepared to perform intestinal procedures independently after
      fellowship. Increased volume and direct involvement of fellows in intestinal
      surgery may improve preparedness for performing intestinal surgery after
      fellowship.

PMID- 29595761
TI  - Cellular Proliferation and Migration of Human Pterygium Cells: Mitomycin Versus
      Small-Molecule Inhibitors.
AB  - PURPOSE: Nutlin is a drug that has been reported to activate p53 in various cell
      lines. We aim to study the effects of Nutlin in pterygium and compare the effects
      of Nutlin and mitomycin C (MMC) in pterygium cell lines. METHODS: Pterygium
      samples (n = 3) were collected during surgical excision. Normal conjunctival
      tissues (n = 3) were collected from another quadrant of the same eye. Cell lines
      were established, and cells from passages 2 to 5 were used. Pterygium and
      conjunctival cells were treated with different doses of Nutlin and MMC. Cell
      proliferation and cell migration were measured. RESULTS: Cell proliferation was
      reduced by 39-fold after treatment with 50 MUM Nutlin. Cell migration was
      inhibited with increasing dosages of Nutlin (95% and 28% after treating with 2
      and 50 MUM Nutlin, respectively). Compared with MMC, Nutlin induced more
      pterygium cell death and less conjunctival cell death at low doses. At 50% lethal
      dose for pterygium cells, 95% of conjunctival cells survived after Nutlin
      treatment, whereas only 63% of conjunctival cells survived after MMC treatment.
      p21 expression was not detectable in MMC-treated pterygium cells but was
      detectable after Nutlin treatment. CONCLUSIONS: In our study, MMC induced cell
      death in pterygium and conjunctival cell lines, whereas Nutlin had a targeted
      impact on pterygium cells. Our results implied that MMC inhibited both pterygium
      cell proliferation and migration through an apoptosis-independent pathway.

PMID- 29595762
TI  - Transplantation Blues: Inadvertent Staining of Amyloid Deposits With Trypan Blue.
AB  - PURPOSE: To describe inadvertent persistent staining of stromal amyloid deposits
      by trypan blue (TB) after penetrating keratoplasty (PK) and Descemet membrane
      endothelial keratoplasty (DMEK) performed in patients with corneal amyloidosis.
      METHODS: Case series of patients with corneal amyloidosis in whom intraoperative
      TB was used. RESULTS: One patient, hospitalized for acute rejection 6 weeks after
      DMEK, presented with an intense blue staining of small, spindle-shaped structures
      in the anterior half of the cornea. DMEK had been performed for endothelial
      failure of a previous PK procedure done 13 years earlier for advanced lattice
      corneal dystrophy (LCD). After 6 months, the stromal blue tattoo persisted with
      impaired visual acuity, and PK was performed. Blue-stained structures were
      amyloid deposits characteristic of LCD recurrence. In parallel, among 85
      consecutive triple procedures (PK + cataract + intraocular lens [IOL]) performed
      over 7 years, in which TB was used, only patients with LCD (n = 18 eyes in 17
      patients) or presumed secondary amyloidosis due to chronic inflammation (n = 1),
      presented an isolated intense blue ring of the graft-host interface. This
      persisted up to 7 years with no clinical consequence. CONCLUSIONS: TB can stain
      corneal amyloid deposits. After PK, staining is limited to the recipient
      peripheral cornea and has no apparent clinical consequence. However, during DMEK
      performed after a failed PK, TB stains fibrils accumulated during slow LCD
      recurrence and scattered on the whole graft. The long-term staining duration
      indicates strong interactions between TB and amyloid.

PMID- 29595763
TI  - Epithelial Keratitis After Cataract Surgery.
AB  - PURPOSE: To evaluate the incidence, related perioperative factors, clinical
      characteristics, and possible etiologies of epithelial keratitis after cataract
      surgery. METHODS: A retrospective chart review of 666 eyes in 666 patients who
      underwent cataract surgery was performed to evaluate the incidence of epithelial
      keratitis and related factors in the postoperative period. RESULTS: Postoperative
      epithelial keratitis developed in 15 eyes. Eleven of the 15 eyes were diagnosed
      with herpes simplex keratitis (HSK); 10 of the 11 eyes were diagnosed by
      polymerase chain reaction, and the remaining 1 eye by clinical diagnosis. All
      patients diagnosed with HSK had no previous clinical history of the infection
      before undergoing cataract surgery. Initially, the diagnosis of all 15 eyes was
      toxic keratitis, but the final diagnosis of 11 of the initial 15 was found to be
      epithelial herpes keratitis. The incision location was shown to be related to the
      occurrence of HSK in our study (P < 0.05). CONCLUSIONS: HSK epithelial keratitis
      after cataract surgery is a relatively uncommon complication and can be
      misdiagnosed in its early disease course because of its relative rarity. This
      study explores the possibility that the temporal corneal penetrating incisional
      approach used in routine cataract surgery interrupts the corneal nerves and
      subsequently can trigger reactivation of HSK.

PMID- 29595765
TI  - Contesting the evidence for non-adaptive plasticity.

PMID- 29595764
TI  - Use of Donor Corneas From Pseudophakic Eyes for Descemet Membrane Endothelial
      Keratoplasty.
AB  - PURPOSE: The prevalence of pseudophakia increases with age and affects more than
      30% of people older than 80 years. Because grafts from older donors seem to be
      more suitable for Descemet membrane endothelial keratoplasty (DMEK) surgery
      rather than grafts from younger donors, eye bank technicians and corneal surgeons
      have to deal with corneas from pseudophakic donors for DMEK graft preparation.
      However, graft preparation from corneas of pseudophakic donors can be more
      complicated. METHODS: We retrospectively analyzed our donor registry for the
      prevalence of pseudophakia. We compared grafts from phakic and pseudophakic
      donors concerning graft survival, rebubbling rates, and endothelial cell loss
      after DMEK surgery. RESULTS: More than 20% of our donors were pseudophakic, of
      which 35% were primarily suitable for transplantation. Regarding the comparison
      of grafts from phakic and pseudophakic donors used for DMEK, we observed
      comparable survival rates (90% after 3 years) and similar endothelial cell loss
      (30% with an endothelial cell density above 1000 cell/mm after 3 years) but
      significantly lower rebubbling rates for grafts from pseudophakic donors (18% vs.
      28%). CONCLUSIONS: Our data strongly suggest that pseudophakic persons should not
      be excluded from corneal donation because success rates after DMEK with grafts
      from pseudophakic eyes are comparable to those with grafts from phakic eyes.
      However, in the eye bank, grafts from pseudophakic donors have a higher primary
      discard rate because of low endothelial cell counts.

PMID- 29595766
TI  - Ghalambor et al. reply.

PMID- 29595769
TI  - Erratum: Non-adaptive plasticity potentiates rapid adaptive evolution of gene
      expression in nature.
AB  - This corrects the article DOI: 10.1038/nature15256.

PMID- 29595767
TI  - Planning chemical syntheses with deep neural networks and symbolic AI.
AB  - To plan the syntheses of small organic molecules, chemists use retrosynthesis, a
      problem-solving technique in which target molecules are recursively transformed
      into increasingly simpler precursors. Computer-aided retrosynthesis would be a
      valuable tool but at present it is slow and provides results of unsatisfactory
      quality. Here we use Monte Carlo tree search and symbolic artificial intelligence
      (AI) to discover retrosynthetic routes. We combined Monte Carlo tree search with
      an expansion policy network that guides the search, and a filter network to pre
      select the most promising retrosynthetic steps. These deep neural networks were
      trained on essentially all reactions ever published in organic chemistry. Our
      system solves for almost twice as many molecules, thirty times faster than the
      traditional computer-aided search method, which is based on extracted rules and
      hand-designed heuristics. In a double-blind AB test, chemists on average
      considered our computer-generated routes to be equivalent to reported literature
      routes.

PMID- 29595768
TI  - Is plasticity caused by single genes?

PMID- 29595771
TI  - Wing origami.

PMID- 29595770
TI  - A galaxy lacking dark matter.
AB  - Studies of galaxy surveys in the context of the cold dark matter paradigm have
      shown that the mass of the dark matter halo and the total stellar mass are
      coupled through a function that varies smoothly with mass. Their average ratio
      Mhalo/Mstars has a minimum of about 30 for galaxies with stellar masses near that
      of the Milky Way (approximately 5 * 1010 solar masses) and increases both towards
      lower masses and towards higher masses. The scatter in this relation is not well
      known; it is generally thought to be less than a factor of two for massive
      galaxies but much larger for dwarf galaxies. Here we report the radial velocities
      of ten luminous globular-cluster-like objects in the ultra-diffuse galaxy NGC1052
      DF2, which has a stellar mass of approximately 2 * 108 solar masses. We infer
      that its velocity dispersion is less than 10.5 kilometres per second with 90 per
      cent confidence, and we determine from this that its total mass within a radius
      of 7.6 kiloparsecs is less than 3.4 * 108 solar masses. This implies that the
      ratio Mhalo/Mstars is of order unity (and consistent with zero), a factor of at
      least 400 lower than expected. NGC1052-DF2 demonstrates that dark matter is not
      always coupled with baryonic matter on galactic scales.

PMID- 29595772
TI  - US science agencies set to win big in budget deal.

PMID- 29595773
TI  - How a bridge brought science closer together.

PMID- 29595774
TI  - Q&A: Elina Berglund on moving from physics to fertility.

PMID- 29595775
TI  - Drug executives should take a Hippocratic oath.

PMID- 29595776
TI  - Ocean scientists work to forecast huge plankton blooms in Arabian Sea.

PMID- 29595777
TI  - The healthy diabetic cavefish conundrum.

PMID- 29595779
TI  - More than one-third of graduate students report being depressed.

PMID- 29595778
TI  - Details matter for contaminants in genetic-engineering kits.

PMID- 29595780
TI  - Climate change as a contributor to human conflict.

PMID- 29595781
TI  - Reduced- calorie diet shows signs of slowing ageing in people.

PMID- 29595782
TI  - Pioneering Alzheimer's study in Colombia zeroes in on enigmatic protein.

PMID- 29595784
TI  - Why laughter in the lab can help your science.

PMID- 29595786
TI  - Conclusion of conflict and climate analysis questioned.

PMID- 29595787
TI  - Four-in-one 3D printer paves way for custom-made robots and phones.

PMID- 29595788
TI  - Boost children's digital intelligence to protect against online threats.

PMID- 29595789
TI  - On the use and abuse of ancient DNA.

PMID- 29595790
TI  - Women feature only rarely as first or last authors in leading journals.

PMID- 29595791
TI  - Athlete brain bank, costly weather and science on social media.

PMID- 29595793
TI  - AI designs organic syntheses.

PMID- 29595795
TI  - Cambridge Analytica controversy must spur researchers to update data ethics.

PMID- 29595796
TI  - Swedish science bounces back.

PMID- 29595798
TI  - Oceans on Mars formed early.

PMID- 29595799
TI  - The tornadoes of sudden cardiac arrest.

PMID- 29595801
TI  - A trio of ion channels takes the heat.

PMID- 29595800
TI  - Critique of conflict and climate analysis is oversimplified.

PMID- 29595802
TI  - Divided by DNA: The uneasy relationship between archaeology and ancient genomics.

PMID- 29595803
TI  - First space mission dedicated to exoplanet atmospheres gets green light.

PMID- 29595804
TI  - Mushrooms: coming soon to a burger near you.

PMID- 29595805
TI  - Cybersecurity needs women.

PMID- 29595806
TI  - Killer T cells show their kinder side.

PMID- 29595809
TI  - AUDIOME: a tiered exome sequencing-based comprehensive gene panel for the
      diagnosis of heterogeneous nonsyndromic sensorineural hearing loss.
AB  - PurposeHereditary hearing loss is highly heterogeneous. To keep up with rapidly
      emerging disease-causing genes, we developed the AUDIOME test for nonsyndromic
      hearing loss (NSHL) using an exome sequencing (ES) platform and targeted analysis
      for the curated genes.MethodsA tiered strategy was implemented for this test.
      Tier 1 includes combined Sanger and targeted deletion analyses of the two most
      common NSHL genes and two mitochondrial genes. Nondiagnostic tier 1 cases are
      subjected to ES and array followed by targeted analysis of the remaining AUDIOME
      genes.ResultsES resulted in good coverage of the selected genes with 98.24% of
      targeted bases at >15 *. A fill-in strategy was developed for the poorly covered
      regions, which generally fell within GC-rich or highly homologous regions.
      Prospective testing of 33 patients with NSHL revealed a diagnosis in 11 (33%) and
      a possible diagnosis in 8 cases (24.2%). Among those, 10 individuals had variants
      in tier 1 genes. The ES data in the remaining nondiagnostic cases are readily
      available for further analysis.ConclusionThe tiered and ES-based test provides an
      efficient and cost-effective diagnostic strategy for NSHL, with the potential to
      reflex to full exome to identify causal changes outside of the AUDIOME
      test.Genetics in Medicine advance online publication, 29 March 2018;
      doi:10.1038/gim.2018.48.

PMID- 29595811
TI  - Familial communication and cascade testing among relatives of BRCA population
      screening participants.
AB  - PURPOSE: Population BRCA1/BRCA2 screening identifies carriers irrespective of
      family history, yet this information is actionable for relatives. We examined
      familial communication rates and cascade testing in the screening setting and
      assessed sociodemographic and psychosocial predictors. METHODS: Participants in a
      BRCA1/BRCA2 screening study of healthy Ashkenazi Jews self-administered a family
      communication questionnaire. Intent to communicate was determined before genetic
      status was known, along with result communication (carriers and noncarriers) 6
      months and 2 years after enrollment. Carriers underwent in-depth interviews and
      provided cascade testing information. RESULTS: In total, 88% (524/595) of
      questionnaire responders and 97% (30/32) of carriers informed at least one
      relative. In multivariate analysis, family history (P = 0.005) and greater
      Satisfaction With Health Decision scores (P < 0.001) predicted communication of
      results. Among carriers' adult first- and second-degree relatives, 71 (48%) had
      cascade testing, more commonly performed in first- (58%) than in second-degree
      relatives (26%, P = 0.0002), and in females (56%) vs. males (36%, P = 0.02). At
      least 11% remained uninformed. CONCLUSION: Familial communication rates and
      characteristics in a screening setting parallel those reported by Cancer Genetics
      clinics. Universal screening circumvents dependence on familial disclosure.
      However, our finding that satisfaction-a potentially modifiable factor-predicts
      communication, raises the hypothesis that improving the testing experience could
      facilitate familial communication.

PMID- 29595810
TI  - Genotype and phenotype correlation in von Hippel-Lindau disease based on
      alteration of the HIF-alpha binding site in VHL protein.
AB  - PURPOSE: Von Hippel-Lindau (VHL) disease is a rare hereditary cancer syndrome
      that reduces life expectancy. We aimed to construct a more valuable genotype
      phenotype correlation based on alterations in VHL protein (pVHL). METHODS: VHL
      patients (n = 339) were recruited and grouped based on mutation types: HIF-alpha
      binding site missense (HM) mutations, non-HIF-alpha binding site missense (nHM)
      mutations, and truncating (TR) mutations. Age-related risks of VHL-associated
      tumors and patient survival were compared. RESULTS: Missense mutations conferred
      an increased risk of pheochromocytoma (HR = 1.854, p = 0.047) compared with
      truncating mutations. The risk of pheochromocytoma was lower in the HM group than
      in the nHM group (HR = 0.298, p = 0.003) but was similar between HM and TR groups
      (HR = 0.901, p = 0.810). Patients in the nHM group had a higher risk of
      pheochromocytoma (HR = 3.447, p < 0.001) and lower risks of central nervous
      system hemangioblastoma (CHB) (HR = 0.700, p = 0.045), renal cell carcinoma (HR =
      0.610, p = 0.024), and pancreatic tumor (HR = 0.382, p < 0.001) than those in the
      combined HM and TR (HMTR) group. Moreover, nHM mutations were independently
      associated with better overall survival (HR = 0.345, p = 0.005) and CHB-specific
      survival (HR = 0.129, p = 0.005) than HMTR mutations. CONCLUSION: The modified
      genotype-phenotype correlation links VHL gene mutation, substrate binding site,
      and phenotypic diversity (penetrance and survival), and provides more accurate
      information for genetic counseling and pathogenesis studies.

PMID- 29595812
TI  - Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to
      assess feasibility and potential impact on prenatal counseling and pregnancy
      management.
AB  - PURPOSE: Unexpected fetal abnormalities occur in 2-5% of pregnancies. While
      traditional cytogenetic and microarray approaches achieve diagnosis in around 40%
      of cases, lack of diagnosis in others impedes parental counseling, informed
      decision making, and pregnancy management. Postnatally exome sequencing yields
      high diagnostic rates, but relies on careful phenotyping to interpret genotype
      results. Here we used a multidisciplinary approach to explore the utility of
      rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as
      an exemplar. METHODS: Parents in pregnancies undergoing invasive testing because
      of sonographic fetal abnormalities, where multidisciplinary review considered
      skeletal dysplasia a likely etiology, were consented for exome trio sequencing
      (both parents and fetus). Variant interpretation focused on a virtual panel of
      240 genes known to cause skeletal dysplasias. RESULTS: Definitive molecular
      diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings
      alone were of sufficient severity for parents to opt for termination. In others,
      molecular diagnosis informed accurate prediction of outcome, improved parental
      counseling, and enabled parents to terminate or continue the pregnancy with
      certainty. CONCLUSION: Trio sequencing with expert multidisciplinary review for
      case selection and data interpretation yields timely, high diagnostic rates in
      fetuses presenting with unexpected skeletal abnormalities. This improves parental
      counseling and pregnancy management.

PMID- 29595813
TI  - FMR1 allele size distribution in 35,000 males and females: a comparison of
      developmental delay and general population cohorts.
AB  - PurposeDevelopmental delay phenotypes have been associated with FMR1 premutation
      (PM: 55-200 CGG repeats) and "gray zone" (GZ: 45-54 CGG repeats) alleles.
      However, these associations have not been confirmed by larger studies to be
      useful in pediatric diagnostic or screening settings.MethodsThis study determined
      the prevalence of PM and GZ alleles in two independent cohorts of 19,076
      pediatric referrals to developmental delay diagnostic testing through Victorian
      Clinical Genetics Service (cohort 1: N = 10,235; cohort 2: N = 8841), compared
      with two independent general population cohorts (newborn screening N = 1997;
      carrier screening by the Victorian Clinical Genetics Service prepair program N =
      14,249).ResultsPM and GZ prevalence rates were not significantly increased (p >
      0.05) in either developmental delay cohort (male PM: 0.12-0.22%; female PM: 0.26
      0.33%; male GZ: 0.68-0.69%; female GZ: 1.59-2.13-%) compared with general
      population cohorts (male PM: 0.20%; female PM: 0.27-0.82%; male GZ: 0.79%; female
      GZ: 1.43-2.51%). Furthermore, CGG size distributions were comparable across
      datasets, with each having a modal value of 29 or 30 and ~1/3 females and ~1/5
      males having at least one allele with <=26 CGG repeats.ConclusionThese data do
      not support the causative link between PM and GZ expansions and developmental
      delay phenotypes in pediatric settings.GENETICS in MEDICINE advance online
      publication, 29 March 2018; doi:10.1038/gim.2018.52.

PMID- 29595815
TI  - Anti-GAD antibody syndrome with concomitant cerebellar ataxia, stiff person
      syndrome, and limbic encephalitis.

PMID- 29595814
TI  - Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost
      effective when applied early in Mendelian disorders.
AB  - PurposeWhole-exome sequencing (WES) has revolutionized Mendelian diagnostics,
      however, there is no consensus on the timing of data review in undiagnosed
      individuals and only preliminary data on the cost-effectiveness of this
      technology. We aimed to assess the utility of WES data reanalysis for diagnosis
      in Mendelian disorders and to analyze the cost-effectiveness of this technology
      compared with a traditional diagnostic pathway.MethodsWES was applied to a cohort
      of 54 patients from 37 families with a variety of Mendelian disorders to identify
      the genetic etiology. Reanalysis was performed after 12 months with an improved
      WES diagnostic pipeline. A comparison was made between costs of a modeled WES
      pathway and a traditional diagnostic pathway in a cohort with intellectual
      disability (ID).ResultsReanalysis of WES data at 12 months improved diagnostic
      success from 30 to 41% due to interim publication of disease genes, expanded
      phenotype data from referrer, and an improved bioinformatics pipeline. Cost
      analysis on the ID cohort showed average cost savings of US$586 (AU$782) for each
      additional diagnosis.ConclusionEarly application of WES in Mendelian disorders is
      cost-effective and reanalysis of an undiagnosed individual at a 12-month time
      point increases total diagnoses by 11%.GENETICS in MEDICINE advance online
      publication, 29 March 2018; doi:10.1038/gim.2018.39.

PMID- 29595816
TI  - Absence and reappearance of N20 response after thiopental withdrawal in
      postanoxic coma.

PMID- 29595817
TI  - Scurvy in the 21st century?: Vitamin C deficiency presenting to the neurologist.

PMID- 29595818
TI  - Hyperekplexia as the presenting symptom of Creutzfeldt-Jakob disease.

PMID- 29595819
TI  - Hypocupremia secondary to excessive zinc supplementation and gastric surgery.

PMID- 29595820
TI  - Multivitamin supplements and energy drinks in pyridoxine megavitaminosis.

PMID- 29595822
TI  - Case reports in your own words: "Real life happens".

PMID- 29595823
TI  - Novel gene variations in early-onset frontotemporal dementia with positive family
      history of neural ceroid lipofuscinosis-1.

PMID- 29595821
TI  - Parkinsonism and dystonia in Lubag disease respond well to high pulse width/low
      frequency globus pallidus interna DBS.

PMID- 29595824
TI  - A rare cause of temporal lobe ring-enhancing lesion.

PMID- 29595825
TI  - Correction: Recurrent Biliary Obstruction Secondary to Portal Biliopathy and the
      Role of Cholangioscopy: A Case Report.
AB  - [This corrects the article DOI: 10.7759/cureus.2046.].

PMID- 29595827
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1756285617749134.].

PMID- 29595826
TI  - Pediatric multiple sclerosis: current perspectives on health behaviors.
AB  - Purpose: Pediatric-onset multiple sclerosis (POMS) accounts for ~5% of all
      multiple sclerosis cases, and has a prevalence of ~10,000 children in the USA.
      POMS is associated with a higher relapse rate, and results in irreversible
      disability on average 10 years earlier than adult-onset multiple sclerosis. Other
      manifestations of POMS include mental and physical fatigue, cognitive impairment,
      and depression. We believe that the health behaviors of physical activity, diet,
      and sleep may have potential benefits in POMS, and present a scoping review of
      the existing literature. Methods: We identified papers by searching three
      electronic databases (PubMed, GoogleScholar, and CINAHL). Search terms included:
      pediatric multiple sclerosis OR pediatric onset multiple sclerosis OR POMS AND
      health behavior OR physical activity OR sleep OR diet OR nutrition OR obesity.
      Papers were included in this review if they were published in English, referenced
      nutrition, diet, obesity, sleep, exercise, or physical activity, and included
      pediatric-onset multiple sclerosis as a primary population. Results: Twenty
      papers were identified via the literature search that addressed health-promoting
      behaviors in POMS, and 11, 8, and 3 papers focused on diet, activity, and sleep,
      respectively. Health-promoting behaviors were associated with markers of disease
      burden in POMS. Physical activity participation was associated with reduced
      relapse rate, disease burden, and sleep/rest fatigue symptoms. Nutritional
      factors, particularly vitamin D intake, may be associated with relapse rate.
      Obesity has been associated with increased risk of developing POMS. POMS is
      associated with better sleep hygiene, and this may benefit fatigue and quality of
      life. Discussion: Participation in health behaviors, particularly physical
      activity, diet, and sleep, may have benefits for POMS. Nevertheless, there are
      currently no interventions targeting promotion of these behaviors and examining
      the benefits of managing the primary and secondary manifestations of POMS.

PMID- 29595828
TI  - Symptomatic intrathecal hypertension.

PMID- 29595829
TI  - Faciobrachial dystonic seizures in an Lgi1 VGKC-complex antibody-mediated
      encephalitis.

PMID- 29595831
TI  - Condensing embryology teaching: a medical student perspective.

PMID- 29595830
TI  - Influence of Dietary Patterns on Plasma Soluble CD14, a Surrogate Marker of Gut
      Barrier Dysfunction.
AB  - Background: Specific foods and nutrients, including alcohol, may contribute to
      gut barrier dysfunction. However, to our knowledge, the influence of whole diets
      is currently unknown. Objective: We aimed to cross-sectionally investigate
      associations of dietary patterns with plasma soluble CD14 (sCD14), which is
      released by macrophages on stimulation with endotoxin and has been used as a
      marker of gut hyperpermeability. Methods: We used food-frequency questionnaire
      data collected from 689 women in the Nurses' Health Study and 509 men in the
      Health Professionals Follow-Up Study. Our principal component analysis identified
      2 dietary patterns: "Western" (higher intakes of red meat, processed meat,
      desserts, and refined grains) and "prudent" (higher intakes of fruits,
      vegetables, fish, and whole grains). In multivariable-adjusted logistic
      regression analyses, we estimated ORs and 95% CIs for high (equal to or greater
      than the median compared with less than the median) sCD14 concentrations in
      quintiles of each dietary pattern. Using logistic regression, we also
      investigated the joint association of the Western dietary pattern and alcohol
      intake or C-reactive protein (CRP) with sCD14 concentrations. Results: Western
      dietary pattern scores were positively associated with sCD14 concentrations (OR:
      1.86; 95% CI: 1.24, 2.79; P-trend = 0.0005; comparing extreme quintiles).
      Analyses of joint associations suggested that the strongest associations with
      higher sCD14 concentrations were for persons with both high Western pattern
      scores and high alcohol intake compared with participants with low scores for
      both (OR: 2.96; 95% CI: 1.61, 5.45) or for participants with both high Western
      pattern scores and high CRP values compared with those with low scores for both
      (OR: 4.11; 95% CI: 2.57, 6.58). The prudent pattern was not associated with sCD14
      concentrations. Conclusions: Higher consumption of the Western dietary pattern is
      associated with a marker of macrophage activation and gut hyperpermeability,
      especially when coupled with high alcohol intake and heightened systemic
      inflammation. Our findings need confirmation in studies with additional markers
      of gut barrier dysfunction.

PMID- 29595832
TI  - What models of change can be used to implement change in postgraduate medical
      education?

PMID- 29595833
TI  - CT perfusion can delineate lacunar infarcts in acute stroke calls.

PMID- 29595834
TI  - A case of familial frontotemporal dementia presenting with malignant catatonia.

PMID- 29595835
TI  - Iatrogenic cerebral arterial and venous gas embolism leading to massive
      hemorrhage, herniation, and death.

PMID- 29595836
TI  - Tourism Contribution to Poverty Alleviation in Kenya: A Dynamic Computable
      General Equilibrium Analysis.
AB  - The aim of this article is to investigate the claim that tourism development can
      be the engine for poverty reduction in Kenya using a dynamic, microsimulation
      computable general equilibrium model. The article improves on the common practice
      in the literature by using the more comprehensive Foster-Greer-Thorbecke (FGT)
      index to measure poverty instead of headcount ratios only. Simulations results
      from previous studies confirm that expansion of the tourism industry will benefit
      different sectors unevenly and will only marginally improve poverty headcount.
      This is mainly due to the contraction of the agricultural sector caused the
      appreciation of the real exchange rates. This article demonstrates that the
      effect on poverty gap and poverty severity is, nevertheless, significant for both
      rural and urban areas with higher impact in the urban areas. Tourism expansion
      enables poorer households to move closer to the poverty line. It is concluded
      that the tourism industry is pro-poor.

PMID- 29595837
TI  - Evaluating persistent altered mental status after status epilepticus.

PMID- 29595838
TI  - Permanent "foreign accent" after cyclosporine encephalopathy in a liver
      transplant patient.

PMID- 29595839
TI  - ACCRETION PROCESSES IN COSMIC SOURCES: The Atmospheres of Accreting White Dwarfs.
AB  - A comparison is presented between the physical processes operative in single
      white dwarfs and the physical processes operative in white dwarfs with donor star
      companions. The physical properties and accretion physics of the hot accreting
      components in close interacting binaries is presented. The N/C abundance anomaly
      seen is ~10% of cataclysmic variables and the presence of absorption lines due to
      heavy elements in suprasolar abundance are discussed. A synthetic spectral
      analysis of the FUSE spectrum of the old nova RR Pic reveals reveals an accretion
      disk with i = 60 degrees , Mwd = 1.0M? and a high accretion rate of 10-8M?/yr.
      New evidence from the FUSE and IUE spectra of the symbiotic system CQ Dra suggest
      it is a triple system consisting of a red giant and a cataclysmic variable
      companion. The hot component in the symbiotic system, RW Hya, consists of a white
      dwarf with a surface temperature of 160,000 K with log(g) = 6.5 and no evidence
      of an accretion disk.

PMID- 29595840
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000480349.].

PMID- 29595841
TI  - Correction: 4-year results from the RAPID-PsA phase 3 randomised placebo
      controlled trial of certolizumab pegol in psoriatic arthritis.
AB  - [This corrects the article DOI: 10.1136/rmdopen-2017-000582.][This corrects the
      article DOI: 10.1136/rmdopen-2017-000582.].

PMID- 29595842
TI  - A case of alcoholic pellagra encephalopathy presenting with spinal myoclonus.

PMID- 29595844
TI  - Porous-carbon-based Mo2C nanocomposites as excellent microwave absorber: a new
      exploration.
AB  - In this study, we report a porous-carbon-based Mo2C nanocomposite (NCs) as the
      microwave absorber via typical carbothermal reduction using metal-organic
      frameworks (MOFs) and polyoxometalates (POMs) as the precursors, which have been
      rarely applied in electromagnetic (EM) wave absorption areas. The elaborately
      designed NCs not only bring about good impedance matching, but also possess
      strong dissipation ability due to the large surface areas and porous features.
      Thanks to the material characteristics as well as structural advantages, the as
      prepared Mo2C/C NCs with 20 wt% sample loading exhibit remarkable microwave
      absorbing performance. The minimum RL value reaches -49.19 dB at matching
      thickness of 2.6 mm, and the best effective bandwidth (RL < -10 dB) of 4.56 GHz
      at 1.70 mm was also achieved. Moreover, the NCs overcome the intrinsic drawback
      of traditional carbon materials, that is, centralized effective absorption always
      occurred at high frequency (>10 GHz) and the minimum RL value of the NCs shifted
      to 9.04 GHz. Clearly, in this study, we not only developed the Mo2C NC as the new
      light absorber, but also paved the way to synthesize other available transition
      metal carbides using MOFs and POMs.

PMID- 29595843
TI  - Reduction-responsive amphiphilic polymeric prodrugs of camptothecin
      polyphosphoester for cancer chemotherapy.
AB  - As one of the promising prodrug strategies, amphiphilic polymeric prodrugs can be
      constructed by conjugating some small molecular hydrophobic anticancer drugs onto
      a hydrophilic biodegradable and biocompatible polymer, which further self
      assembles into nanoparticles with controllable drug loading. Here, a
      biocompatible and biodegradable polyphosphoester and a broad-spectrum anticancer
      drug camptothecin (CPT) were selected as model compounds. We first designed and
      synthesized a novel cyclic phosphoester monomer (CPTSP) containing a disulfide
      bond linker and CPT as a side group. Then a reduction-responsive amphiphilic
      polymeric prodrug (PCPTSP-co-PEEP) was prepared through the ring-opening
      copolymerization of CPTSP and a common cyclic phosphoester monomer containing
      ethyl (EEP) as the side group, which was initiated by benzyl alcohol with 1,8
      diazabicycloundec-7-ene (DBU) and thiourea (TU) as catalysts. The resulting
      PCPTSP-co-PEEPs could self-assemble into micelles in water due to their
      hydrophilic polyphosphoester main chain and some hydrophobic CPT side groups. The
      average size and the drug loading content of these micelles can be controlled by
      adjusting the feed molar ratio of EEP and CPTSP. The average hydrodynamic
      diameter increased from 190 nm to 250 nm when the molar ratio of EEP/CPTSP was
      adjusted from 9/1 to 49/1. These micelles possessed appropriate stability under
      physiological conditions and degraded in the reduction medium according to their
      change in size monitored by DLS measurement. Their reduction-responsive
      properties were also confirmed by the in vitro drug release behavior. Moreover,
      these micelles could enter into HT29 tumor cells via endocytosis and released CPT
      efficiently to inhibit their proliferation. The in vivo tumor inhibition rate of
      these polymeric prodrugs was 73.4%, which was about two fold that for free CPT
      (36.5%). This approach of polymeric prodrugs based on polyphosphoesters can be
      extended to other anticancer drugs to construct smart drug delivery systems for
      cancer treatment.

PMID- 29595845
TI  - Real-time detection of the nanoparticle induced phytotoxicity in rice root tip
      through the visible red emissions of Eu3+ ions.
AB  - Phytotoxicity is one of the most important factors involved in the reduction of
      crop production. With the introduction of NaBiF4 nanoparticles, the effect of the
      particle size (>50 nm) on rice development was systematically studied. Through
      the exogenous treatment of multiple concentrations of nanoparticles, the primary
      root length, lateral root number, and lateral root length were significantly
      inhibited under higher content of nanoparticles, but more crown root formation
      was induced, which might be due to phytotoxicity. With the help of the red
      emission of the Eu3+-activated NaBiF4 nanoparticles, we could infer that the
      nanoparticles were accumulated in the root tip cells in the division and
      elongation zone but not in the mature region. Additionally, the investigation on
      the influence of the studied nanoparticles on the gene level and the expression
      of phytotoxicity related genes was performed to further identify the effect of
      the nanoparticles on the rice root development. These results potentially explain
      the effect of larger nanoparticles on phytotoxicity in the plant roots.

PMID- 29595846
TI  - alpha-Methyl phenylglycines by asymmetric alpha-arylation of alanine and their
      effect on the conformational preference of helical Aib foldamers.
AB  - alpha-Arylated alanine derivatives were made enantioselectively by migratory
      rearrangement of a urea derivative using (R,R)-pseudoephedrine as a chiral
      auxiliary. Incorporation of a single residue of the product alpha-methyl
      phenylglycine into an otherwise achiral oligomer of aminoisobutyric acid oligomer
      induced a preferred screw sense, detectable by a NMR reporter located at the
      remote terminus of the oligomer. The magnitude of the screw sense induction was
      greater when the chiral residue was located at the N-terminus of the foldamer,
      and in some cases the sense of induction was opposite to that of related alpha
      methylated amino acids with alpha-substituents other than aryl.

PMID- 29595847
TI  - Direct C4-H phosphonation of 8-hydroxyquinoline derivatives employing photoredox
      catalysis and silver catalysis.
AB  - A simple and efficient protocol for the C4-H phosphonation of 8-hydroxyquinoline
      derivatives was developed under a photoredox/silver(i) cocatalysis system,
      providing a new approach to phosphonated 8-hydroxyquinoline derivatives. Note
      that the reaction did not occur at the C5 site, but regioselectively at an
      unusual C4 site. Moreover, the reaction proceeded smoothly under mild reaction
      conditions (a catalytic amount of silver salt and room temperature) with good
      functional group compatibility.

PMID- 29595849
TI  - Cobalt phosphide/carbon dots composite as an efficient electrocatalyst for oxygen
      evolution reaction.
AB  - The oxygen evolution reaction (OER) is a promising energy conversion system,
      which has been studied a lot in recent years. However, owing to the high
      overpotential and sluggish kinetics of the OER, an efficient electrocatalyst is
      necessary to lower the overpotential and accelerate the reaction. In this paper,
      we report a cobalt phosphide (CoP)/carbon dots (CDs) composite as an
      electrocatalyst for the OER for the first time. A facile two-step method was used
      to synthesize the CoP/CDs composite and the concentration of CDs in the composite
      was further regulated. The experimental results show that when the amount of CDs
      in the composite is 6 mg (28.79 wt%C), the obtained CoP/CDs composite exhibits
      optimal electrocatalytic activity (with an overpotential of 400 mV in 1 M KOH at
      a current density of 10 mA cm-2) and high stability towards the OER. The good
      electrocatalytic activity of the composite is attributed to the small size of CoP
      and CDs and rapid electron transfer of CDs.

PMID- 29595850
TI  - On the thickness of the double layer in ionic liquids.
AB  - In this study, we examined the thickness of the electrical double layer (EDL) in
      ionic liquids using density functional theory (DFT) calculations and molecular
      dynamics (MD) simulations. We focused on BF4- anion adsorption from the 1-ethyl-3
      methylimidazolium tetrafluoroborate (EMImBF4) ionic liquid on the Au(111)
      surface. At both DFT and MD levels, we evaluated the capacitance-potential
      dependence for the Helmholtz model of the interface. Using MD simulations, we
      also explored a more realistic, multilayer EDL model accounting for the ion
      layering. Concurrent analysis of the DFT and MD results provides a ground for
      thinking whether the electrical double layer in ionic liquids is one- or multi
      ionic-layer thick.

PMID- 29595848
TI  - Multivalent conjugates of basic fibroblast growth factor enhance in vitro
      proliferation and migration of endothelial cells.
AB  - Growth factors hold great promise for regenerative therapies. However, their
      clinical use has been halted by poor efficacy and rapid clearance from tissue,
      necessitating the delivery of extremely high doses to achieve clinical
      effectiveness which has raised safety concerns. Thus, strategies to either
      enhance growth factor activity at low doses or to increase their residence time
      within target tissues are necessary for clinical success. In this study, we
      generated multivalent conjugates (MVCs) of basic fibroblast growth factor (bFGF),
      a key growth factor involved in angiogenesis and wound healing, to hyaluronic
      acid (HyA) polymer chains. Multivalent bFGF conjugates (mvbFGF) were fabricated
      with minimal non-specific interaction observed between bFGF and the HyA chain.
      The hydrodynamic radii of mvbFGF ranged from ~50 to ~75 nm for conjugation ratios
      of bFGF to HyA chains at low (10 : 1) and high (30 : 1) feed ratios,
      respectively. The mvbFGF demonstrated enhanced bioactivity compared to
      unconjugated bFGF in assays of cell proliferation and migration, processes
      critical to angiogenesis and tissue regeneration. The 30 : 1 mvbFGF outperformed
      the 10 : 1 conjugate, which could be due to either FGF receptor clustering or
      interference with receptor mediated internalization and signal deactivation. This
      study simultaneously investigated the role of both protein to polymer ratio and
      multivalent conjugate size on their bioactivity, and determined that increasing
      the protein-to-polymer ratio and conjugate size resulted in greater cell
      bioactivity.

PMID- 29595851
TI  - Highly sensitive flexible three-axis tactile sensors based on the interface
      contact resistance of microstructured graphene.
AB  - The lack of high-performance tactile sensors, especially for pressure/force, is a
      huge obstacle for the widespread application of intelligent robots. Current
      pressure sensors are often operated in the high range of pressure and normal
      direction, showing a little ability in the low range of pressure and three-axis
      direction simultaneously. Herein, a highly sensitive flexible tactile sensor with
      three-axis force sensing capacity is presented by combining microstructured
      polydimethylsiloxane (PDMS) arrays and a reduced graphene oxide (rGO) film. The
      deformation of microstructured rGO/PDMS results in a change in the contact area
      between the rGO film and electrode, leading to a high sensitivity of -1.71 kPa-1
      in the low range pressure of 0-225 Pa with a fast response time of 6 ms at a
      large feature size of 100 MUm. To realize three-axis sensing, a sensing unit was
      built up, which was composed of the adjacent four parts of patterns and
      electrodes underneath a bump. A mechanical model of the exerted spatial force was
      established to calculate each axis force component via the deformation of the
      rGO/PDMS pattern. The experimental results show that the current difference
      between the adjacent two parts has a strong relationship with the applied force.
      As a proof of concept, we have demonstrated a 3 * 3 array sensor for arbitrary
      force sensing. Our tactile sensor would be used in transmitting information from
      a gentle spatial force and would exhibit broad applications as e-skin in
      integrated robots.

PMID- 29595852
TI  - Composite-dissolving microneedle patches for chemotherapy and photothermal
      therapy in superficial tumor treatment.
AB  - A combination of chemotherapy and photothermal therapy (PTT) has emerged as a
      promising strategy for cancer therapy. To ensure that the chemotherapeutic drug
      and photothermal agent can be simultaneously delivered to the tumor site to exert
      their synergistic effects, a safe and efficient delivery system is needed.
      Herein, we fabricated doxorubicin hydrochloride (DOX)- and indocyanine green
      (ICG)-loaded microneedle (MN) patches (PVP@DOX/MSN@ICG) using a two-step casting
      process. Mesoporous silica nanoparticles (MSNs) were used to improve the ICG
      stability and avoid reducing its PTT efficiency in vivo. The MN patches exhibited
      a good skin penetration ability, and the tips of the MN patches were dissolved by
      the interstitial fluid to release DOX and ICG at the tumor sites. Under 808 nm
      laser irradiation within 2 min, the local temperature in the tumor quickly
      reached 48  degrees C at a low power of 0.34 W cm-2. A combination of
      chemotherapy and PTT for PVP@DOX/MSN@ICG MN patches may maximally induce human
      osteosarcoma MG-63 cells in vitro. Moreover, the in vivo results showed that
      PVP@DOX/MSN@ICG MN patches had the best antitumor effects because of synergistic
      chemotherapy and PTT. Therefore, the composite-dissolving MN patch is a promising
      strategy for enhancing the antitumor effect of chemotherapy alone and shows the
      potential for the synergistic therapy of superficial tumors.

PMID- 29595853
TI  - Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the
      androgen-independent growth of prostate cancer cells.
AB  - Phenethyl isothiocyanate (PEITC) is a naturally occurring compound found in some
      cruciferous vegetables. Dibenzoylmethane (DBM) is a minor constituent of
      licorice. Both compounds have been shown to exert anticancer activities. In the
      present study, we determined the effects of PEITC and DBM alone or in combination
      on androgen-independent growth of human prostate cancer cells cultured in vitro
      and prostate VCaP xenograft tumors in severe combined immunodeficient (SCID)
      mice. PEITC and DBM in combination had stronger effects on inhibiting the growth
      and inducing apoptosis than either compound alone in cultured prostate cancer
      cells. The combination also strongly inhibited cell migration and the formation
      of tumorspheres in VCaP cells. Mechanistic studies showed that the combined
      effects of PEITC and DBM on growth inhibition and apoptosis were associated with
      suppression of nuclear factor-kappaB (NF-kappaB), and a decrease in the levels of
      survivin and phospho-Akt (pAkt). In the in vivo study, SCID mice bearing VCaP
      tumors were surgically castrated and treated with PEITC and/or DBM. Treatment
      with PEITC and DBM in combination resulted in a strong inhibition of the
      progression of androgen-dependent VCaP prostate tumors to androgen independence.
      Our results indicate that administration of DBM and PEITC in combination may be
      an effective strategy for inhibiting/delaying the progression of prostate cancer
      to androgen independence.

PMID- 29595856
TI  - Predicting an unconventional facile route to metallaanthracenes.
AB  - Metallaaromatics have attracted considerable interest from both experimentalists
      and theoreticians since the first prediction of metallabenzenes, in which a CH
      group is replaced by a transition metal fragment. In comparison with monocyclic
      metallabenzenes and bicyclic metallanaphthalenes, tricyclic metallaanthracenes
      are quite less developed. Thus, it is urgent to explore synthetic methods for
      this rare system. Here we report a thorough investigation on the formation of
      metallaanthracenes from transition metal fluorenyl complexes via density
      functional theory calculations. We systematically investigate how metal centres,
      ligands, and substituents affect such a rearrangement. Our results indicate that
      formation of metallaanthracenes could become thermodynamically and kinetically
      favourable from transition metal fluorenyl complexes by tuning suitable metal
      centres, ligands, and substituents, suggesting an unconventional facile way to
      prepare such rare tricyclic metallaaromatics for experimentalists, which is in
      sharp contrast to the traditional isomerisation of metallabenzenes to
      cyclopentadienyl complexes.

PMID- 29595858
TI  - Calycosin directly improves perivascular adipose tissue dysfunction by
      upregulating the adiponectin/AMPK/eNOS pathway in obese mice.
AB  - Perivascular adipose tissue (PVAT) loses its anti-contractile activity in
      obesity. Calycosin, the major bioactive isoflavonoid, was shown to protect
      endothelial function. However, effects of calycosin on PVAT function in obesity
      remain unclear. We aimed to investigate the effects of calycosin on the anti
      contractile activity of PVAT in obese mice and its potential mechanisms. Obesity
      in mice was induced with a high-fat diet, with or without calycosin treatment.
      Thoracic aorta responses to phenylephrine were determined. AMP protein kinase
      (AMPK) and endothelial nitric oxide synthase (eNOS) levels were analyzed by
      western blotting. Adiponectin, TNF-alpha levels and superoxide production were
      measured in the PVAT. Calycosin treatment significantly increased the anti
      contractile response of PVAT, which was impaired in obese mice. This beneficial
      effect of calycosin was eliminated by treatments of blocking adiponectin, AMPK or
      eNOS. Similar results were observed for calycosin treatment ex vivo. Treatment of
      obese mice with calycosin significantly increased adiponectin levels, activated
      AMPK and eNOS phosphorylation and reduced superoxide production and TNF-alpha
      levels in PVAT. Our results indicated that calycosin restored PVAT induced anti
      contractile activity and affected PVAT function through the adiponectin/AMPK/eNOS
      pathway in obese mice.

PMID- 29595859
TI  - Nanocrystal heterostructures of LiCoO2 with conformal passivating shells.
AB  - Stabilization of electrode-electrolyte interfaces is required to increase the
      energy stored in battery electrodes. Introducing redox-inactive ions on the
      electrode surface minimizes deleterious side reactions without affecting the bulk
      properties. A synthetic challenge exists to grow such layers conformally at each
      primary particle, to fully passivate interfaces that are buried in the final
      electrode architecture. The development of methods of sequential colloidal growth
      of complex oxides and overlayers, enabled by surfactant interactions, would
      provide novel means to advance toward this goal. Here, nanocrystals composed of
      LiCoO2, a commercially relevant material for high energy devices, were grown with
      a shell enriched in Al3+, deposited conformally through a one-pot colloidal
      synthetic method. The effects of synthetic conditions on the composition of the
      Al-rich shell and the corresponding electrochemical performance were
      investigated. The modified nanocrystals showed enhanced electrochemical
      properties, while maintaining carrier transport.

PMID- 29595861
TI  - Bis(selenobenzoato)dibutyltin(iv) as a single source precursor for the synthesis
      of SnSe nanosheets and their photo-electrochemical study for water splitting.
AB  - A new organo-tin complex has been synthesized and used as a single source
      precursor for the synthesis of SnSe nanosheets by the hot injection method and
      thin films by the aerosol assisted chemical vapor deposition (AACVD) method. The
      films were deposited on glass substrates at three different temperatures. The
      textural quality and preferential growth were found to be significantly altered
      by changes in the deposition temperature. Oleylamine capped nanosheets and the as
      deposited thin films by AACVD were characterized by powder X-ray diffraction (p
      XRD) and microscopic techniques. The thin films were also studied by Raman
      spectroscopy. The stoichiometry is marginally affected by temperature, and all
      films were slightly selenium deficient. The synthesized material was also
      evaluated for the photoelectrochemical (PEC) splitting of water. The PEC study
      revealed the bifunctional nature of the material, which can be applied for both
      the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), by
      switching the applied potential.

PMID- 29595860
TI  - Relationship between copper(ii) complexes with FomA adhesin fragments of F.
      nucleatum and colorectal cancer. Coordination pattern and ability to promote ROS
      production.
AB  - The copper(ii) ion binding of the Ac-KGHGNG-NH2 and Ac-PTVHNE-NH2 fragments of
      FomA adhesin from Fusobacterium nucleatum was studied using potentiometry, UV
      Vis, CD, EPR and DFT techniques. The coordination pattern was described in a wide
      range of pH values. Ligands begin interactions with metal ions using imidazole
      nitrogen. At pH 6.8 (a value typical of the large intestine environment), the
      metal ion was coordinated by the 3N donor atoms {Nim, 2 * N-amide} in both cases.
      However, the copper(ii) ion was bound more effectively by the Ac-PTVHNE-NH2
      peptide. The formation of reactive oxygen species (ROS) was studied by UV-Vis and
      fluorescence spectroscopy, as well as gel electrophoresis in the presence of H2O2
      and/or ascorbic acid. The complexes generated ROS in the highest amounts among
      all compounds. Moreover, they stimulated the CT26 cell line (mouse colon
      carcinoma) to produce ROS which lead to oxidative stress. It was also determined
      that such radicals took part in the plasmid degradation mechanism.

PMID- 29595866
TI  - Post mortem determination of (beta)-tryptase for the diagnosis of anaphylaxis:
      looking for a reasonable cut-off.

PMID- 29595864
TI  - Etiology of chronic skin lesions in subjects with peripheral arterial disease.
AB  - INTRODUCTION: Skin lesions can be defined as lesions that result in loss of
      tissues and their joints, and often this cutaneous skin process is a primary or
      secondary consequence of the structural changes in the skin itself. Subjects with
      peripheral arteripathies that develop chronic skin lesions in the lower
      extremities of the Western world are constantly increasing. We conducted a study
      on the etiologic incidence of chronic skin lesions in peripheral arterial disease
      CSLpa subjects in the lower limbs compared to subjects with chronic skin lesions
      CSL (controls). MATERIALS AND METHODS: 30 subjects with peripheral atheropathies
      PA (22 F - 8 M mean age 74,5 +/- 4,9) and with chronic skin lesions (CSLpa) in
      the lower limbs "A" group were admitted to our study according to a randomized
      and compared to 30 no peripheral atheropathies subjects (19 F-11 M, mean age 81,5
      +/- 7,3 - controls) group B with chronic skin lesions (CSL). These two groups "A"
      and "B" have been studied and compared on the basis of infectious etiology
      responsible for the infectious skin process. RESULTS: In the subjects of the "A"
      group we found a 12 positive assay of 40.0% of the examinations, while in the
      group "B" we achieved a total cultured positivity of 9 cases corresponding to
      30.0% of the examinations . For the number of bacterial species identified for
      "A" group we obtained 3 mono microbial and 6 poly microbial bacteriological tests
      and for group "B" we observed 7 mono microbial and 2 poly microbial tests. All
      bacteriological isolates showed "in vitro" sensitivity to satisfactory
      ciprofloxacin with MICs range of 0.78-1.56mg/L. The data observed after 4 weeks
      after the amniotic membrane (MA) in the two study groups A and B were
      respectively the following: and for group A 50% scarring, 46.6% partial
      resolution and in one case worsening for the B-healing group in 63.3%, the
      partial resolution in the remaining 36.6. CONCLUSIONS: The data from this study
      show a different etiology between subjects with CSLpa than subjects with CSL.
      This phenomenon confirms an alteration of the skin microbioma of subjects with
      peripheral arteriopathy and chronic skin lesions with modification of the
      opportunistic role of some species of cutaneous bacterial flora.

PMID- 29595865
TI  - Germline Editing: Editors Cautionary.
AB  - This communication is regarding the recent editing of the genome of the human
      embryo with CRISPR/Cas9 which generated a debate amongst the biological
      scientists around the world. Editing human germline genes may act as godsend in
      some serious genetic and other disorders as the genes related to these disorders
      can be replaced effectively. The scientists are in dilemma whether the human
      germline gene modification is a boon or bane for the human society. Though
      editing human germline genes may be an answer to many serious genetic disorders
      however; it may have unpredictable effects on future generations. The ethical
      issues regarding the germline editing need further discussion which may have
      implications on human race and on-going human evolution. Thus, the researchers
      need to be doubly cautious and some stringent regulations should be framed
      regarding the various aspects of germ line gene modifications and any potential
      conflict with nature for future outcome.

PMID- 29595867
TI  - Aesthetic satisfaction in lip and palate clefts: a comparative study between
      secondary and tertiary bone grafting.
AB  - Lip and palate cleft represent one of the most frequently occurring congenital
      deformity, which includes dental anomalies, such as variation in tooth number and
      position. In case of hypodontia implant-prosthetic rehabilitation offers
      significant advantages in terms of function, aesthetics and quality of life and
      bone graft is usually needed. Secondary bone grafting, generally performed in the
      mixed dentition phase (years 8-11) seems to be the most successful method to
      allow for rehabilitation. It's often necessary to perform a tertiary bone
      grafting in adult age in order to achieve better bone quantity and quality before
      implant placement. Aim of this retrospective study was to evaluate the aesthetic
      perception that patients had of themselves comparing dental implants placed in
      tertiary grafted alveolar cleft sites with a previous secondary grafting to only
      secondary grafting. Between 2009 and 2012, fourteen alveolar cleft were treated
      with implant rehabilitation and eleven of them received tertiary bone grafting
      six months prior to implant placement. All patients were questioned to give a
      score from 1 to 10 their aesthetic satisfaction of their smile before and after
      implant rehabilitation and during pre-surgery provisional rehabilitation. At the
      end of their prosthesis rehabilitation patients who received tertiary bone
      grafting resulted more satisfied than those who had secondary bone grafting only
      (9.5 vs 8).

PMID- 29595868
TI  - Iatrogenic hypoparathyroidism after surgery for retrosternal goitre. A single
      centre retrospective analysis.
AB  - AIM: The aim of this study is to assess, retrospectively, the incidence of
      secondary hypoparathyroidism after total thyroidectomy in patients with
      retrosternal goitre. MATERIAL AND METHODS: From January 2009 to September 2015,
      622 patients who undergone total thyroidectomy for goitre, were retrospectively
      observed. The patients were divided into two group: Group A, including 58
      patients with retrosternal goitre and Group B, including 562 patients with in
      situ goitre. Those patients with diseases of the parathyroid glands, assumption
      of drugs modifying calcium metabolism and who received blood transfusions before
      or after surgery, were excluded from the study. In both groups, a total
      thyroidectomy was performed under general anaesthesia. The upper and lower
      parathyroid glands in both groups were observed in situ as well. All surgical
      specimens underwent histological examination. RESULTS: Transient hypocalcaemia
      was observed in a higher percentage in group A (15% vs 7%, P <0.05). The mean
      hospital stay was greater in group A (P <0.05). There were no statistically
      differences between the two groups in terms of permanent hypocalcaemia and post
      operative blood ionized calcium (72hours and 1 month). CONCLUSIONS: Many efforts
      should be made to respect parathyroids during total thyroidectomy in retrosternal
      goitre; greater attention should be given to inferior parathyroid glands that
      should be displayed, respecting the vasculature and performing a terminal lower
      thyroid artery ligation in order to reduce the risk of transient hypocalcaemia
      and - as a consequence - the average hospital stay.

PMID- 29595869
TI  - Implementing carrier screening for cystic fibrosis outside the clinic: ethical
      analysis in the light of the personalist view.
AB  - BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive genetic disease. Two
      models for screening CF are normally used: newborn screening and population-based
      CF carrier screening. In turn, there are three main models of population-based CF
      carrier screening: prenatal carrier screening, preconception carrier screening,
      and carrier screening outside clinical settings. AIM: To evaluate, in the light
      of the personalist view, the use of carrier screenings for CF outside the clinic,
      i.e. in non-clinical settings, such as school and workplaces. METHODS: Analysis
      has been carried out according to the "Personalist approach" (also called
      "Triangular model"), an ethical method for performing ethical analysis within HTA
      process. It includes factual, anthropological and ethical data in a
      ''triangular'' normative reflection process. FINDINGS: Implementing carrier
      screening for cystic fibrosis outside the clinical settings allows acquisition of
      knowledge for informing reproductive choices, that can be considered as valuable;
      benefit-risk ratio seems to be not much favorable; autonomous and responsible
      decisions can be taken only under certain conditions; economic advantage is
      difficult to determine; therefore, from a personalist view, implementing carrier
      screenings outside the clinic seems not to be ethically justified. CONCLUSIONS:
      In accordance with the personalist perspective, public health programs providing
      carrier screenings outside the clinic should not be implemented.

PMID- 29595870
TI  - Law on advance health care directives: a medical perspective.
AB  - The paper's authors aim to elaborate on law 22 dicembre 2017, n. 219 , designed
      to regulate informed consent practices and advance health care directives", which
      has sparked a passionate debate centered on the substantial innovation achieved
      over the past decades in bio-medical science and at the same time, the noteworthy
      accomplishments made in enforcing human and personal rights. Within the paper,
      article three is delved into, which covers the creation of the so-called DAT
      ("Disposizioni anticipate di trattamento", advance health care directives), by
      which patients, in light of possible future incapacity to choose, can express
      their convictions and decisions on how to be treated and their consent or dissent
      to undergo treatments and procedures, including artificial nutrition and
      hydration. The authors peruse the new law's provisions through a medical
      perspective, and observe how they are heavily tilted towards patient choice, thus
      making doctors little more than mere tools of such decisions.

PMID- 29595871
TI  - Guidelines and best practices: remarks on the Gelli-Bianco law.
AB  - The paper's authors aim to elaborate on the innovations brought by law n.
      24/2017, issued by the Italian Parliament with a close focus on art. 5, which
      pertains to the drafting of guidelines and the adoption of best practices. The
      guidelines constitute in fact an element of innovation brought by the above
      mentioned law, and compliance with them can shield from possible liability those
      health care professionals who find themselves embroiled in professional accidents
      while in the fulfillment of their duties. Besides, there are several critical
      aspects within the law that need to be highlighted as well. As far as best
      practices are concerned, the lawmakers who drafted the legislation make no
      mention as to the standards of evidence needed in order to characterize any given
      professional behavior as "best practice". The reform appears unlikely to be
      effective in providing doctors with clear behavioral standards, thus reducing the
      margin for liability claims against them.

PMID- 29595872
TI  - Headaches Through a Woman's Life.
AB  - Importance: Headaches affect women across their life span, with menses,
      pregnancy, and menopause being times that pose unique challenges in diagnosis and
      treatment. The correct diagnosis and treatment of headache can prevent
      unnecessary interventions, the worsening of chronic headache disorders, and
      complications of secondary headaches. Objective: The objective of this article is
      to educate women's health care providers about the diagnosis, differential
      diagnosis, and treatment of headache during menses, pregnancy, the puerperium,
      and menopause to improve the quality of care for women with chronic and acute
      headache. Evidence Acquisition: Current articles were reviewed addressing
      headache during menses, pregnancy, the postpartum period, and menopause. Articles
      with the highest level of evidence were compiled in this article to provide a
      summary of recommendations. Results: Multiple diagnostic and therapeutic options
      for chronic and acute headache are available for women regardless of their stage
      in life or comorbidities. Conclusions and Relevance: The effects of headaches
      span a woman's life span, with puberty and menopause being times of increased
      frequency. Pregnancy is an at-risk time for women to develop secondary headache
      disorders. All women's health care providers should know how to screen for,
      diagnose, and treat headache at all stages of a woman's life. Effective treatment
      options are available for acute and chronic headache both during and outside
      pregnancy.

PMID- 29595873
TI  - Pain Management for First-Trimester Uterine Aspiration.
AB  - Importance: First-trimester uterine aspiration can easily be performed in the
      office setting if adequate pain management for the patient is achieved. It is
      important for clinicians to understand evidence-based approaches for pain control
      to ensure a safe and efficient procedure. Objective: This article reviews the
      literature regarding pharmacologic and nonpharmacologic pain control options for
      first-trimester abortion performed in the clinical setting. Preoperative,
      procedural, and postoperative pain control are all reviewed. Evidence
      Acquisition: Authors searched the online database PubMed for relevant published
      literature through January 2018. To identify possible publications for review,
      the key word "abortion" was paired with the following key words: "pain," "pain
      control," "pain management," "aspiration," "paracervical block," "sedation, "non
      pharmacologic," and "post-operative." Results: Optimizing pain control for first
      trimester uterine aspiration may involve interventions before, during, and after
      the surgery. Evidence shows patients benefit from premedication with nonsteroidal
      anti-inflammatory drugs, a defined paracervical block technique, and an option to
      use one of several nonpharmacologic interventions. Conclusions and Relevance:
      Pain management for first-trimester uterine aspiration should be individualized
      for optimal patient satisfaction. Evidence supports multiple approaches to
      support this individualization. Targeted interventions before, during, and after
      the procedure should be offered to improve procedure experience and satisfaction.

PMID- 29595874
TI  - Temporal analysis of cardiovascular control and function following incomplete T3
      and T10 spinal cord injury in rodents.
AB  - Spinal cord injury (SCI) is a devastating condition that results in whole-body
      dysfunction, notably cardiovascular (CV) disruption and disease. Injury-induced
      destruction of autonomic pathways in conjunction with a progressive decline in
      physical fitness contribute to the poor CV status of SCI individuals. Despite the
      wide use of exercise training as a therapeutic option to reduce CV dysfunction,
      little is known about the acute hemodynamic responses to the exercise itself. We
      investigated CV responses to an exercise challenge (swimming) following both high
      and low thoracic contusion to determine if the CV system is able to respond
      appropriately to the challenge of swimming. Blood pressure (BP) telemetry and
      echocardiography were used to track the progression of dysfunction in rodents
      with T3 and T10 SCI (n = 8 each) for 10 weeks postcontusion. At 1 week
      postinjury, all animals displayed a drastic decline in heart rate (HR) during the
      exercise challenge, likely a consequence of neurogenic shock. Furthermore, over
      time, all groups developed a progressive inability to maintain BP within a narrow
      range during the exercise challenge despite displaying normal hemodynamic
      parameters at rest. Echocardiography of T10 animals revealed no persistent signs
      of cardiac dysfunction; T3 animals exhibited a transient decline in systolic
      function that returned to preinjury levels by 10 weeks postinjury. Novel evidence
      provided here illustrates that incomplete injuries produce hemodynamic
      instability that only becomes apparent during an exercise challenge. Further,
      this dysfunction lasts into the chronic phase of disease progression despite
      significant recovery of hindlimb locomotion and cardiac function.

PMID- 29595875
TI  - Impaired autonomic function in adolescents born preterm.
AB  - Preterm birth temporarily disrupts autonomic nervous system (ANS) development,
      and the long-term impacts of disrupted fetal development are unclear in children.
      Abnormal cardiac ANS function is associated with worse health outcomes, and has
      been identified as a risk factor for cardiovascular disease. We used heart rate
      variability (HRV) in the time domain (standard deviation of RR intervals, SDRR;
      and root means squared of successive differences, RMSSD) and frequency domain
      (high frequency, HF; and low frequency, LF) at rest, as well as heart rate
      recovery (HRR) following maximal exercise, to assess autonomic function in
      adolescent children born preterm. Adolescents born preterm (less than 36 weeks
      gestation at birth) in 2003 and 2004 and healthy age-matched full-term controls
      participated. Wilcoxon Rank Sum tests were used to compare variables between
      control and preterm groups. Twenty-one adolescents born preterm and 20 term-born
      controls enrolled in the study. Preterm-born subjects had lower time-domain HRV,
      including SDRR (69.1 +/- 33.8 vs. 110.1 +/- 33.0 msec, respectively, P = 0.008)
      and RMSSD (58.8 +/- 38.2 vs. 101.5 +/- 36.2 msec, respectively, P = 0.012), with
      higher LF variability in preterm subjects. HRR after maximal exercise was slower
      in preterm-born subjects at 1 min (30 +/- 12 vs. 39 +/- 9 bpm, respectively, P =
      0.013) and 2 min (52 +/- 10 vs. 60 +/- 10 bpm, respectively, P = 0.016). This
      study is the first report of autonomic dysfunction in adolescents born premature.
      Given prior association of impaired HRV with adult cardiovascular disease,
      additional investigations into the mechanisms of autonomic dysfunction in this
      population are warranted.

PMID- 29595876
TI  - Exercise mitigates the effects of hyperhomocysteinemia on adverse muscle
      remodeling.
AB  - Hyperhomocysteinemia (HHcy) is known for causing inflammation and vascular
      remodeling, particularly through production of reactive oxygen species (ROS) and
      matrix metalloproteinase-9 (MMP-9) activation. Although its effect on the
      skeletal muscle is unclear, HHcy can cause skeletal muscle weakness and
      functional impairment by induction of inflammatory mediators and macrophage
      mediated injury. Exercise has been shown to reduce homocysteine levels and
      therefore, could serve as a promising intervention for HHcy. The purpose of this
      study was to investigate whether HHcy causes skeletal muscle fibrosis through
      induction of inflammation and determine whether exercise can mitigate these
      effects. C57BL/6J (WT) and CBS+/- (HHcy) mice were administered a 6 weeks
      treadmill exercise protocol. Hindlimb perfusion was measured via laser Doppler.
      Measurement of skeletal muscle protein expression was done by western blot.
      Levels of skeletal muscle MMP-9 mRNA were determined by qPCR. Collagen deposition
      in the skeletal muscle was measured using Masson's trichrome staining. In CBS+/-
      mice, HHcy manifested with decreased body weight and femoral artery lumen
      diameter, as well as a trend of lower hindlimb perfusion. These mice displayed
      increased wall to lumen ratio, mean arterial blood pressure, collagen deposition,
      and elevated myostatin protein expression. Exercise mitigated the effects above
      in CBS+/- mice. Skeletal muscle from CBS+/- mice had elevated markers of
      remodeling and hypoxia: iNOS, EMMPRIN, and MMP-9. We conclude that HHcy causes
      skeletal muscle fibrosis possibly through induction of EMMPRIN/MMP-9 and exercise
      is capable of mitigating the pathologies associated with HHcy.

PMID- 29595878
TI  - AKT2 is the predominant AKT isoform expressed in human skeletal muscle.
AB  - Skeletal muscle physiology and metabolism are regulated by complex networks of
      intracellular signaling pathways. Among many of these pathways, the protein
      kinase AKT plays a prominent role. While three AKT isoforms have been identified
      (AKT1, AKT2, and AKT3), surprisingly little is known regarding isoform-specific
      expression of AKT in human skeletal muscle. To address this, we examined the
      expressions of each AKT isoform in muscle biopsy samples collected from the
      vastus lateralis of healthy male adults at rest. In muscle, AKT2 was the most
      highly expressed AKT transcript, exhibiting a 15.4-fold increase over AKT1 and
      AKT3 transcripts. Next, the abundance of AKT protein isoforms was determined
      using antibody immunoprecipitation followed by Liquid Chromatography-Parallel
      Reaction Monitoring/Mass Spectrometry. Immunoprecipitation was performed using
      either mouse or rabbit pan AKT antibodies that were immunoreactive with all three
      AKT isoforms. We found that AKT2 was the most abundant AKT isoform in human
      skeletal muscle (4.2-fold greater than AKT1 using the rabbit antibody and 1.6
      fold greater than AKT1 using the mouse antibody). AKT3 was virtually
      undetectable. Next, cultured primary human myoblasts were virally-transduced with
      cDNAs encoding either wild-type (WT) or kinase-inactive AKT1 (AKT1-K179M) or AKT2
      (AKT2-K181M) and allowed to terminally differentiate. Myotubes expressing WT-AKT1
      or WT-AKT2 showed enhanced fusion compared to control myotubes, while myotubes
      expressing AKT1-K179M showed a 14% reduction in fusion. Myotubes expressing AKT2
      K181M displayed 63% decreased fusion compared to control. Together, these data
      identify AKT2 as the most highly-expressed AKT isoform in human skeletal muscle
      and as the principal AKT isoform regulating human myoblast differentiation.

PMID- 29595877
TI  - Effects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence
      associated microRNAs.
AB  - The aim of this study was to determine, in vitro, the effects of X4 and R5 HIV-1
      gp120 and Tat on: (1) endothelial cell senescence and (2) endothelial cell
      microRNA (miR) expression. Endothelial cells were treated with media without and
      with: R5 gp120 (100 ng/mL), X4 gp120 (100 ng/mL), or Tat (500 ng/mL) for 24 h and
      stained for senescence-associated beta-galactosidase (SA-beta-gal). Cell
      expression of miR-34a, miR-217, and miR-146a was determined by RT-PCR. X4 and R5
      gp120 and Tat significantly increased (~100%) cellular senescence versus control.
      X4 gp120 significantly increased cell expression of miR-34a (1.60 +/- 0.04 fold)
      and miR-217 (1.52 +/- 0.18), but not miR-146a (1.25 +/- 0.32). R5 gp120
      significantly increased miR-34a (1.23 +/- 0.07) and decreased miR-146a (0.56 +/-
      0.07). Tat significantly increased miR-34a (1.49 +/- 0.16) and decreased miR-146a
      (0.55 +/- 0.23). R5 and Tat had no effect on miR-217 (1.05 +/- 0.13 and 1.06 +/-
      0.24; respectively). HIV-1 gp120 (X4 and R5) and Tat promote endothelial cell
      senescence and dysregulation of senescence-associated miRs.

PMID- 29595880
TI  - Male apoE*3-Leiden.CETP mice on high-fat high-cholesterol diet exhibit a biphasic
      dyslipidemic response, mimicking the changes in plasma lipids observed through
      life in men.

PMID- 29595879
TI  - Capturing the multifactorial nature of ARDS - "Two-hit" approach to model murine
      acute lung injury.
AB  - Severe acute respiratory distress syndrome (ARDS) presents typically with an
      initializing event, followed by the need for mechanical ventilation. Most animal
      models of ALI are limited by the fact that they focus on a singular cause of
      acute lung injury (ALI) and therefore fail to mimic the complex, multifactorial
      pathobiology of ARDS. To better capture this scenario, we provide a comprehensive
      characterization of models of ALI combining two injuries: intra tracheal (i.t.)
      instillation of LPS or hypochloric acid (HCl) followed by ventilator-induced lung
      injury (VILI). We hypothesized, that mice pretreated with LPS or HCl prior to
      VILI and thus receiving a ("two-hit injury") will sustain a superadditive lung
      injury when compared to VILI. Mice were allocated to following treatment groups:
      control with i.t. NaCl, ventilation with low peak inspiratory pressure (PIP),
      i.t. HCl, i.t. LPS, VILI (high PIP), HCl i.t. followed by VILI and LPS i.t.
      followed by VILI. Severity of injury was determined by protein content and MPO
      activity in bronchoalveolar lavage (BAL), the expression of inflammatory
      cytokines and histopathology. Mice subjected to VILI after HCl or LPS
      instillation displayed augmented lung injury, compared to singular lung injury.
      However, mice that received i.t. LPS prior to VILI showed significantly increased
      inflammatory lung injury compared to animals that underwent i.t. HCl followed by
      VILI. The two-hit lung injury models described, resulting in additive but
      differential acute lung injury recaptures the clinical relevant multifactorial
      etiology of ALI and could be a valuable tool in translational research.

PMID- 29595882
TI  - High-Prevalence and Low-Intensity Ichthyophonus Infections in Pacific Halibut.
AB  - Ichthyophonus occurred at high prevalence but low intensity in Pacific Halibut
      Hippoglossus stenolepis throughout the West Coast of North America, ranging from
      coastal Oregon to the Bering Sea. Infection prevalence in adults was variable on
      spatial and temporal scales, with the lowest prevalence typically occurring on
      the edges of the geographic range and highest prevalence consistently occurring
      inside Prince William Sound, Alaska (58-77%). Additionally, intra-annual
      differences occurred at Albatross-Portlock, Alaska (71% versus 32% within 2012),
      and interannual differences occurred along coastal Oregon (50% in 2012 versus 12%
      in 2015). The infection prevalence was influenced by host age, increasing from 3%
      or less among the youngest cohorts (age <= 6) to 39-54% among age-9-17 cohorts,
      then decreasing to 27% among the oldest (age-18+) cohorts. There was little
      indication of significant disease impacts to Pacific Halibut, as the intensity of
      infection was uniformly low and length at age was similar between infected and
      uninfected cohorts. These results suggest that Ichthyophonus in Pacific Halibut
      currently represents a stable parasite-host paradigm in the North Pacific.

PMID- 29595883
TI  - Comparison of Sampling and Detection Methods for Chinook Salmon and Steelhead
      Naturally Infected with Myxobolus cerebralis.
AB  - Myxobolus cerebralis (Mc) is a myxozoan parasite causing whirling disease in
      hatchery- and natural-origin salmonids. To minimize spread of this parasite and
      the incidence of its associated disease, fish health professionals routinely
      screen fish for Mc before stocking or moving the fish to Mc-free waters. Sample
      collection for Mc traditionally entails lethal sampling of cranial tissue
      followed by pepsin-trypsin digest (PTD) and screening of the sample for mature
      myxobolid myxospores (PTD method); however, nonlethal sampling methods would be
      advantageous in some circumstances, such as when dealing with rare or otherwise
      valuable fish. Accordingly, we compared Mc detections in cranial cartilage by
      using the PTD method with PCR assays of fin biopsies collected from juvenile
      Chinook Salmon Oncorhynchus tshawytscha and adult steelhead O. mykiss. Cranial
      samples were also analyzed using PCR methods for comparative purposes. Results
      indicated that Mc could be detected by PCR in fin clips, but the results
      generated by this approach differed significantly from those associated with PTD-
      and/or PCR-based analysis of cranial cartilage samples. Polymerase chain reaction
      based analysis-of individual head samples and head digest pools in both species
      as well as fins in steelhead-yielded more positive detections than PTD analysis
      alone. The PCR-based analysis of head and fin tissues yielded different Mc
      detection rates in both species, but the nature of the detection disparity varied
      depending on the species and/or life stage of the fish. We conclude that for
      lethal cranial samples, neither PTD nor PCR should be used alone, but using these
      techniques in concert may provide the most complete and accurate estimation of Mc
      presence in a group of salmonids. If imperiled or highly valuable fish are in
      question, nonlethal fin samples may be used to generate some information
      regarding Mc status, with the understanding that parasite DNA detections do not
      necessarily signify mature infections or disease.

PMID- 29595884
TI  - Swimming Endurance in Juvenile Chinook Salmon Infected with Salmincola
      californiensis.
AB  - Juvenile Chinook Salmon Oncorhynchus tshawytscha moving downstream through
      tributaries of the upper Willamette River basin can spend months in reservoirs
      created by dams. While residing in the reservoirs, they often obtain heavy
      infections of the freshwater parasitic copepod Salmincola californiensis. The
      physiologic effect these parasites have on salmonids is poorly understood. We
      developed a method to infect juvenile Chinook Salmon in a laboratory with the
      copepodid stage of S. californiensis. Infected and uninfected fish were subjected
      to a swimming challenge to ascertain swimming endurance. Severity of gill damage
      was assessed using a dissecting microscope. Juvenile Chinook Salmon naturally
      infected with S. californiensis in Cougar Reservoir, Oregon, were also challenged
      and compared with their lab-infected counterparts. Copepod infection greatly
      impaired the swimming ability of laboratory fish, and the naturally infected fish
      were entirely incapable of swimming at low velocity. Chinook Salmon collected in
      the wild were more heavily infected than the laboratory fish and had trouble
      surviving collection and transport to our laboratory. The intensity of infection
      and severity of gill damage were positively correlated with diminished swimming
      ability, suggesting that heavy infection with copepods impairs gas exchange and
      osmotic regulation, which likely results in diminished fitness and decreased
      survival of infected fish.

PMID- 29595881
TI  - The influence of thoracic gas compression and airflow density dependence on the
      assessment of pulmonary function at high altitude.
AB  - The purpose of this report was to illustrate how thoracic gas compression (TGC)
      artifact, and differences in air density, may together conflate the
      interpretation of changes in the forced expiratory flows (FEFs) at high altitude
      (>2400 m). Twenty-four adults (10 women; 44 +/- 15 year) with normal baseline
      pulmonary function (>90% predicted) completed a 12-day sojourn at Mt.
      Kilimanjaro. Participants were assessed at Moshi (Day 0, 853 m) and at Barafu
      Camp (Day 9, 4837 m). Typical maximal expiratory flow-volume (MEFV) curves were
      obtained in accordance with ATS/ERS guidelines, and were either: (1) left
      unadjusted; (2) adjusted for TGC by constructing a "maximal perimeter" MEFV
      curve; or (3) adjusted for both TGC and differences in air density between
      altitudes. Forced vital capacity (FVC) was lower at Barafu compared with Moshi
      camp (5.19 +/- 1.29 L vs. 5.40 +/- 1.45 L, P < 0.05). Unadjusted data indicated
      no difference in the mid-expiratory flows (FEF25-75% ) between altitudes (? +
      0.03 +/- 0.53 L sec-1 ; ? + 1.2 +/- 11.9%). Conversely, TGC-adjusted data
      revealed that FEF25-75% was significantly improved by sojourning at high altitude
      (? + 0.58 +/- 0.78 L sec-1 ; ? + 12.9 +/- 16.5%, P < 0.05). Finally, when data
      were adjusted for TGC and air density, FEFs were "less than expected" due to the
      lower air density at Barafu compared with Moshi camp (?-0.54 +/- 0.68 L sec-1 ; ?
      10.9 +/- 13.0%, P < 0.05), indicating a mild obstructive defect had developed on
      ascent to high altitude. These findings clearly demonstrate the influence that
      TGC artifact, and differences in air density, bear on flow-volume data;
      consequently, it is imperative that future investigators adjust for, or at least
      acknowledge, these confounding factors when comparing FEFs between altitudes.

PMID- 29595885
TI  - Identification of Differentially Regulated Edwardsiella ictaluri Proteins During
      Catfish Serum Treatment.
AB  - Edwardsiella ictaluri is a facultative, intracellular, gram-negative bacterium
      that causes enteric septicemia of catfish (ESC). Edwardsiella ictaluri is known
      to be resistant to defense mechanisms present in catfish serum, which might aid
      in its use of a host's bloodstream to become septicemic. However, the precise
      mechanisms of the survival of E. ictaluri in host serum are not known. Analysis
      of the response of E. ictaluri to the host serum treatment at a proteomic level
      might aid in the elucidation of its adaptation mechanisms against defense
      mechanisms present in catfish serum. Thus, the objective of this study was to
      identify differentially regulated proteins of E. ictaluri upon exposure to naive
      catfish serum. Two-dimensional difference gel electrophoresis (2D-DIGE) followed
      by in-gel trypsin digestion and MALDI-TOF/TOF analysis were used for
      identification of differentially expressed E. ictaluri proteins. A total of 19
      differentially regulated proteins (7 up- and 12 downregulated) were identified.
      Among those were four putative immunogenic proteins, two chaperones and eight
      proteins involved in the translational process, two nucleic acid degradation and
      integration proteins, two intermediary metabolism proteins, and one iron-ion
      binding protein. Further research focusing on the functions of these
      differentially expressed proteins may reveal their roles in host adaptation by E.
      ictaluri.

PMID- 29595886
TI  - Toxicity of Potassium Chloride Compared to Sodium Chloride for Zebra Mussel
      Decontamination.
AB  - The use of chemicals to decontaminate watercraft and/or equipment after exposure
      to zebra mussels Dreissena polymorpha is one method of decontamination that has
      been recommended by multiple government agencies in the United States. The ideal
      chemical to be used for decontamination would be inexpensive and easily obtained,
      would have no or limited effect on nontarget species, and would be relatively
      environmentally friendly. Two chemicals that have been tested are potassium
      chloride (KCl) and sodium chloride (NaCl). The toxicity of each chemical to both
      adult zebra mussels and veliger larvae was examined. Sodium chloride was less
      effective at causing mortality than KCl within the exposure periods tested. Adult
      mussels required a 4* longer exposure period to exhibit complete mortality when
      exposed to NaCl at 30,000 mg/L (24 h) compared to KCl (6 h). At 10,000 mg/L, NaCl
      took 8* longer (96 h) than KCl (12 h) to cause 100% mortality of adult mussels.
      Veligers that were exposed to KCl at 1,250 mg/L required a 12-h exposure to
      attain complete mortality, while those exposed to NaCl at 10,000 mg/L required an
      18-h exposure to exhibit the same result. To determine whether KCl is more
      advantageous as a decontamination chemical, the cost and chemical availability
      must be researched.

PMID- 29595887
TI  - Histological Alterations in Pacific Oysters Crassostrea gigas that Survived a
      Summer Mortality Event in Baja California, Mexico.
AB  - A mortality episode (>90%) of triploid and diploid Pacific oysters Crassostrea
      gigas cultured in Baja California Sur occurred during summer 2012, coinciding
      with a thermal anomaly, an algal bloom, and low oxygen values. To help explain
      the cause of the mortalities, histological analyses and molecular tests for
      specific pathogens (ostreid herpesvirus 1 [OsHV-1] and Perkinsus marinus) were
      performed on oysters surviving at the end of the episode. Triploid oysters showed
      a high percentage of males (43%) and hermaphrodites (30%); 93% of these oysters
      were in the gonadic reabsorption stage, and in some cases, hemocytes completely
      filled the lumen of the gonadic follicles. Oysters presented large areas with
      severe hemocyte infiltration that extended toward the digestive gland. Diploid
      oysters showed similar gonad alterations. None of samples showed histological or
      molecular evidence of OsHV-1 or P. marinus. Histological alterations can be
      related to physiological disorders caused by the mechanism driving summer
      mortality. This is the first case history of a summer mortality episode among
      Pacific oysters in Mexico.

PMID- 29595888
TI  - Humoral Immune Responses to Select Marine Bacteria in Loggerhead Sea Turtles
      Caretta caretta and Kemp's Ridley Sea Turtles Lepidochelys kempii from the
      Southeastern United States.
AB  - Serum from Kemp's ridley sea turtles Lepidochelys kempii and loggerhead sea
      turtles Caretta caretta was collected during summer in 2011, 2012, and 2013.
      Serum immunoglobulin Y (IgY) recognition of lysate proteins from nine bacterial
      species and whole bacterium-specific IgY titers to these pathogens were
      quantified. Serum and purified IgY recognized proteins of all bacteria, with
      protein recognition for some species being more pronounced than others.
      Circulating IgY titers against Vibrio vulnificus, V. anguillarum, Erysipelothrix
      rhusiopathiae, and Brevundimonas vesicularis changed over the years in Kemp's
      ridley sea turtles, while IgY titers against V. vulnificus, Escherichia coli, V.
      parahaemolyticus, B. vesicularis, and Mycobacterium marinum were different in
      loggerhead sea turtles. Serum lysozyme activity was constant for loggerhead sea
      turtles over the 3 years, while activity in Kemp's ridley sea turtles was lower
      in 2011 and 2012 than in 2013. Blood packed cell volume, glucose, and serum
      protein levels were comparable to those of healthy sea turtles in previous
      studies; therefore, this study provides baseline information on antibody
      responses in healthy wild sea turtles.

PMID- 29595889
TI  - Dietary Onion or Ginger Modulates the Stress Response and Susceptibility to
      Vibrio harveyi JML1 Infection in Brown-marbled Grouper Epinephelus fuscoguttatus
      Juveniles.
AB  - Onion Allium cepa and ginger Zingiber officinale have health-promoting properties
      that qualify them as functional foods. The effect of repeated acute stressors was
      examined in juvenile Brown-marbled Grouper Epinephelus fuscoguttatus that were
      fed four diets supplemented with onion at 1.8%, ginger at 1.8%, vitamin C at
      0.86%, and beta-glucan at 0.8% of the diet. The non-supplemented diet served as
      the control. After 12 weeks of feeding, fish were exposed to stressors and were
      experimentally infected with a fish pathogen, the bacterium Vibrio harveyi JML1.
      After repeated exposure to hypoxia, cortisol levels rose significantly in the non
      supplemented fish compared to those fed onion, ginger, beta-glucan, or vitamin C.
      Within groups, postexposure cortisol levels in the onion-, ginger-, and vitamin C
      fed fish did not change relative to pre-stress levels, whereas significant
      increases in poststress values were observed in the control and beta-glucan
      groups. The net cortisol increase was also significantly greater in the non
      supplemented group compared to the supplemented groups. The net cortisol increase
      did not vary among the supplemented groups except that the beta-glucan-fed group
      exhibited a higher net increase than the onion-fed group. Similarly, repeated
      acute exposure to osmotic stress significantly increased the plasma cortisol
      level in the non-supplemented group compared to groups that received supplements;
      no differences were found in the supplemented groups except the beta-glucan
      group. Within groups, significant increases in poststress values relative to pre
      stress levels were found only in the control and beta-glucan groups. Repeated
      acute exposure to hypoxia significantly increased cumulative mortality in the
      control group compared to the supplemented groups (except the beta-glucan group),
      whereas repeated exposure to acute osmotic stress significantly increased
      cumulative mortality only in the control group 10 d after infection with V.
      harveyi JML1. Based on our collective results, most of the supplemented groups
      performed better than the control, but the best supplements were onion and ginger
      in terms of enhancing stress tolerance and increasing survival of Brown-marbled
      Grouper upon infection with V. harveyi JML1.

PMID- 29595891
TI  - Guideline Summary: Medication Safety.

PMID- 29595890
TI  - Risk Factors Associated with Mortality of Age-0 Smallmouth Bass in the
      Susquehanna River Basin, Pennsylvania.
AB  - Evidence of disease and mortalities of young of the year (age-0) Smallmouth Bass
      Micropterus dolomieu has occurred during the late spring and summer in many parts
      of the Susquehanna River watershed since 2005. To better understand contributing
      factors, fish collected from multiple areas throughout the watershed as well as
      out-of-basin reference populations (Allegheny and Delaware River basins;
      experimental ponds, Kearneysville, West Virginia) were examined grossly and
      histologically for abnormalities. Tissue contaminant concentrations were
      determined from whole-body homogenates, and water contaminant concentrations were
      estimated using time-integrated passive samplers at selected sites. Observed or
      isolated pathogens included bacteria, predominantly motile Aeromonas spp. and
      Flavobacterium columnare; largemouth bass virus, and parasites, including
      trematode metacercariae, cestodes, and the myxozoan Myxobolus inornatus. Although
      these pathogens were found in age-0 Smallmouth Bass from multiple sites, no one
      pathogen was consistently associated with mortality. Chemicals detected in tissue
      included polychlorinated biphenyl (PCB) congeners, organochlorine, and current
      use pesticides. Pyraclostrobin, PCB congeners 170 and 187, cis-chlordane and
      trans-nonachlor were detected in all Susquehanna watershed samples but rarely in
      samples from the reference site. The findings support the idea that there is no
      single cause for disease of age-0 Smallmouth Bass; rather the cumulative effects
      of co-infections and potential immunomodulation by environmental stressors during
      a sensitive developmental life stage may lead to mortality. Identifying the most
      important risk factors will be necessary for more in-depth analyses of individual
      stressors and better management of the habitat and fish populations.

PMID- 29595892
TI  - Pediatric Perioperative Nurses and the Ethics of Organ Donation After Cardiac
      Death.
AB  - Pediatric perioperative nurses are experiencing increased opportunities to
      participate in donations after cardiac death. An increased public awareness
      regarding transplantation has inspired more people to donate than in previous
      years. The demand for transplantable organs has led to opportunities that have
      increased donor candidates including living donors and cardiac death donors.
      Cardiac death in children is often sudden and unexpected, and is an emotional
      time not only for the family members but also for the hospital staff members,
      including perioperative nurses. However, when perioperative nurses adhere to
      standards and guidelines, they can perform their responsibilities in an ethical
      and compassionate manner and assist their team in doing so. This article reviews
      the guiding principles of pediatric organ donation after cardiac death, the
      phases of the process, and the ethical and moral issues surrounding donation.

PMID- 29595893
TI  - Postoperative strategies aimed at preventing surgical site infections.

PMID- 29595894
TI  - The Key to Safety: Harmonized Care.

PMID- 29595895
TI  - Guideline Quick View: Team Communication.

PMID- 29595896
TI  - Educational Opportunities.

PMID- 29595897
TI  - The Future of Wound Care.

PMID- 29595899
TI  - Guideline Implementation: Medication Safety: 1.5 www.aornjournal.org/content/cme.

PMID- 29595902
TI  - The Future of Data-Driven Wound Care.
AB  - Care for patients with chronic wounds can be complex, and the chances of poor
      outcomes are high if wound care is not optimized through evidence-based
      protocols. Tracking and managing every variable and comorbidity in patients with
      wounds is difficult despite the increasing use of wound-specific electronic
      medical records. Harnessing the power of big data analytics to help nurses and
      physicians provide optimized care based on the care provided to millions of
      patients can result in better outcomes. Numerous applications of machine learning
      toward workflow improvements, inpatient monitoring, outpatient communication, and
      hospital operations can improve overall efficiency and efficacy of care delivery
      in and out of the hospital, while reducing adverse events and complications. This
      article provides an overview of the application of big data analytics and machine
      learning in health care, highlights important recent advances, and discusses how
      these technologies may revolutionize advanced wound care.

PMID- 29595900
TI  - A Perioperative Approach to Increase Limb Salvage When Treating Foot Ulcers in
      Patients With Diabetes.
AB  - Foot ulceration in patients with diabetes increases the risk of lower extremity
      amputation. Major amputations produce substantial adverse consequences, increase
      length of hospital stay, diminish quality of life, and increase mortality. In
      this article, we describe approaches that decrease amputations and improve the
      quality of life for patients with diabetes and foot ulcers. We highlight the role
      of the perioperative nurse, who is essential to providing optimal patient care in
      the perioperative period. Perioperative care of patients with diabetes involves
      providing optimal surveillance for a break in the skin of the foot, screening for
      neuropathy, following guidelines for foot ulcer infections, preparing for
      pathophysiology-based debridement, using adjuvant therapies, and offloading the
      patient's affected foot. Nurses should understand the disease process and
      pathophysiology and how to use these approaches in the perioperative setting to
      assist in curtailing the morbidity and mortality associated with foot ulcers in
      patients with diabetes.

PMID- 29595903
TI  - Clinical Issues-April 2018: 1.2 www.aornjournal.org/content/cme.

PMID- 29595904
TI  - New technology for postdischarge surgical site infection monitoring.

PMID- 29595906
TI  - Did You Know?

PMID- 29595905
TI  - Perioperative Care of the Breastfeeding Patient.
AB  - Nurses providing surgical care in nonobstetrical ambulatory surgery centers or
      specialty hospitals without traditional lactation resources may need to care for
      patients who are breastfeeding. Nurses in these settings play an important role
      in supporting and protecting the breastfeeding relationship for nursing mothers
      separated from their infants during illness or surgical procedures. It is
      important for care providers to understand how hospitalization and the
      medications administered before, during, and after a surgical procedure affect
      mothers who are breastfeeding their infants. This article examines the effects of
      hospitalization on breastfeeding and focuses on preoperative and postoperative
      care considerations, including medication use, radiology imaging, interrupting
      and resuming breastfeeding, breast assessment, and milk storage.

PMID- 29595907
TI  - Evidence appraisal of Meakin LB, Gilman OP, Parsons KJ, Burton NJ, Langley-Hobbs
      SJ. Colored indicator undergloves increase the detection of glove perforations by
      surgeons during small animal orthopedic surgery: a randomized controlled trial.
      Vet Surg. 2016;45(6):709-1714.

PMID- 29595908
TI  - Wrong-Time Error With High-Alert Medication.

PMID- 29595909
TI  - Hyperbaric Oxygen Therapy: Indications, Contraindications, and Use at a Tertiary
      Care Center: 1.3 www.aornjournal.org/content/cme.

PMID- 29595910
TI  - Preparing for a Centers for Medicare & Medicaid Services Survey.

PMID- 29595911
TI  - Radical cystectomy.

PMID- 29595912
TI  - Perioperative Anticoagulation Management.

PMID- 29595913
TI  - Past injurious exercise attenuates activation of primary calcium-dependent injury
      pathways in skeletal muscle during subsequent exercise.
AB  - Past contraction-induced skeletal muscle injury reduces the degree of subsequent
      injury; this phenomenon is called the "repeated bout effect (RBE)." This study
      addresses the mechanisms underlying the RBE, focusing on primary calcium
      dependent injury pathways. Wistar rats were subdivided into single injury (SI)
      and repeated injury (RI) groups. At age 10 weeks, the right gastrocnemius muscle
      in each rat in the RI group was subjected to strenuous eccentric contractions
      (ECs). Subsequently, mild ECs were imposed on the same muscle of each rat at 14
      weeks of age in both groups. One day after the exercise, the RI group showed a
      lower strength deficit than did the SI group, and neither group manifested any
      increase in membrane permeability. The concentration of protein carbonyls and
      activation of total calpain increased after ECs given at the age of 14 weeks.
      Nonetheless, these increases were lower in the RI group than in the SI group.
      Furthermore, calcium-dependent autolysis of calpain-1 and calpain-3 in the RI
      group was diminished as compared with that in the SI group. Although peak ankle
      joint torque and total force generation during ECs at the age of 14 weeks were
      similar between the two groups, phosphorylation of JNK (Thr183 /Tyr185 ), an
      indicator of mechanical stress applied to a muscle, was lower in the RI group
      than in the SI group. These findings suggest that activation of the primary
      calcium-dependent injury pathways is attenuated by past injurious exercise, and
      mechanical stress applied to muscle fibers during ECs may decrease in the RBE.

PMID- 29595914
TI  - Uromodulin deficiency alters tubular injury and interstitial inflammation but not
      fibrosis in experimental obstructive nephropathy.
AB  - Human GWAS and Mendelian genetic studies have linked polymorphic variants and
      mutations in the human uromodulin gene (UMOD) with chronic kidney disease. The
      primary function of this kidney-specific and secreted protein remains elusive.
      This study investigated whether UMOD deficiency modified responses to unilateral
      ureteral obstruction (UUO)-induced kidney injury. Kidneys harvested from groups
      of wild-type (UMOD+/+) and knockout (UMOD-/-) male mice (n = 7-10 each) were
      studied on days 7, 14, and 21. Compared to sham kidneys, UMOD protein levels
      increased 9-13x after UUO and were associated with increased urinary UMOD levels.
      Kidney KIM-1 protein levels were higher in the UMOD-/- groups at all time-points
      (4-14x). The UMOD-/- groups also had higher KIM-1 kidney-to-urine relative ratios
      (5-35x). In vitro studies using KIM-1 expressing 769-P cells showed lower KIM-1
      levels in the presence of UMOD protein. Levels of proapoptotic genes and the
      epithelial cell apoptotic protein marker M30 were significantly lower in the UMOD
      /- groups. Both M30 and KIM-1 colocalized with intraluminal UMOD protein
      deposits. Interstitial inflammation was less intense in the UMOD-/- groups. Renal
      fibrosis severity (kidney collagen mRNA and protein) was similar in both
      genotypic groups on days 7, 14, and 21. Our findings suggest a role for UMOD
      dependent inhibition of KIM-1 expression and its apoptotic cell scavenging
      responses during chronic obstruction-associated tubular injury.

PMID- 29595915
TI  - Dual treatment with a fixed ratio of glucagon and insulin increases the
      therapeutic window of insulin in diabetic rats.
AB  - The current available insulin therapies decrease blood glucose but are associated
      with the risk of developing hypoglycemia. Glucagon is a counter regulatory
      hormone and we hypothesize that a fixed ratio of insulin and a long-acting
      glucagon-analogue can reduce the risk of hypoglycemia. To define an appropriate
      ratio we tested two fixed glucagon doses (3.5 and 10 nmol/kg) in combination with
      increasing doses of insulin in diabetic rats. We observed a plateau in blood
      glucose at 15.2 mmol/L with 10 nmol/kg of the glucagon-analogue. The mechanism
      behind this plateau, protecting against hypoglycemia, was investigated by
      measuring the glucose output, cAMP production, and hormone binding in primary rat
      hepatocytes. While glucose output could contribute to the observed plateau in
      blood glucose, cAMP response or hormone binding did not explain the observation.
      Though such plateau indicated decreased risk of hypoglycemia a full normalization
      of blood glucose was still needed. Based on the data obtained with 3.5 nmol/kg of
      the glucagon-analogue, a 1:23 (glucagon-analogue:insulin) ratio was chosen and a
      dose-response was performed in diabetic rats. At low doses (<=20 nmol/kg),
      insulin and the 1:23 ratio showed similar efficacy of lowering blood glucose.
      Interestingly, the insulin-dose resulting in hypoglycemia was increased from 40
      nmol/kg insulin alone to 160 nmol/kg insulin in the 1:23 ratio. Analysis of the
      liver glycogen content at the end of the experiment showed that the highest dose
      in the 1:23 ratio almost emptied the liver from glycogen. Thus, liver glycogen is
      essential for the protective effect of glucagon in hypoglycemia.

PMID- 29595916
TI  - The complement system in hypertension and renal damage in the Dahl SS rat.
AB  - Evidence indicates the immune system is important in development of hypertension
      and kidney disease. In the Dahl Salt-Sensitive (SS) rat model, lymphocytes play a
      role in development of hypertension and kidney damage after increased sodium
      intake. Recent transcriptomic analyses demonstrate upregulation of the innate
      immune complement system in the kidney of Dahl SS rat fed a high-salt diet,
      leading us to hypothesize that inhibition of complement activation would
      attenuate development of hypertension and kidney damage. Male Dahl SS rats on a
      low salt (0.4% NaCl) diet were instrumented with telemeters for continuous
      monitoring of arterial blood pressure. Animals received saline vehicle (Control)
      or sCR1, a soluble form of endogenous Complement Receptor 1 (CR1; CD35) that
      inhibits complement activation. At Day 0, rats were switched to high salt (4.0%
      NaCl) diet and assigned to sCR1 (15 mg/kg per day) or Control groups with daily
      ip injections either days 1-7 or days 14-18. Urine was collected overnight for
      determination of albumin excretion. Treatment with sCR1, either immediately after
      high-salt diet was initiated, or at days 14-18, did not alter development of
      hypertension or albuminuria. The sCR1 dose effectively inhibited total hemolytic
      complement activity as well as C3a generation. High salt caused an increase in
      message for complement regulator Cd59, with minimal change in Crry that controls
      the C3 convertase. Thus, innate immune complement activation in the circulation
      is not critical for development of hypertension and kidney damage due to
      increased sodium intake, and therapeutic manipulation of the complement system is
      not indicated in salt-sensitive hypertension.

PMID- 29595917
TI  - Inhibition of overexpression of Gialpha proteins and nitroxidative stress
      contribute to sodium nitroprusside-induced attenuation of high blood pressure in
      SHR.
AB  - We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously
      hypertensive rats (SHR) exhibit enhanced expression of Gialpha proteins which was
      attributed to the decreased levels of nitric oxide (NO), because elevation of the
      intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso
      N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Gialpha
      proteins. Since the enhanced expression of Gialpha proteins is implicated in the
      pathogenesis of hypertension, the present study was undertaken to investigate if
      treatment of SHR with SNP could also attenuate the development of high blood
      pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal
      injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2
      weeks into SHR attenuated the high blood pressure by about 80 mmHg without
      affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels
      of superoxide anion (O2- ), hydrogen peroxide (H2 O2 ), peroxynitrite (ONOO- ),
      and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the
      overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4,
      P22phox , and P47phox , and Gialpha proteins in VSMC from SHR were also
      attenuated by SNP treatment. On the other hand, SNP treatment augmented the
      decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These
      results suggest that SNP treatment attenuates the development of high BP in SHR
      through the elevation of intracellular levels of cGMP and inhibition of the
      enhanced levels of Gialpha proteins and nitroxidative stress.

PMID- 29595919
TI  - Data Quality at the Indiana State Cancer Registry: An Evaluation of Timeliness by
      Cancer Type and Year.
AB  - BACKGROUND: Central cancer registries collect tumor-related data to monitor
      incidence rates and support population-based research. One concern with using
      registry data for research is timeliness of reporting. Timeliness has
      beenrecognized as an important data characteristic by both the Centers for
      Disease Control and Prevention and the NationalAcademy of Medicine. Yet, few
      studies in the United States have systematically measured timeliness. The purpose
      of thisstudy is to evaluate timeliness in cancer-case reporting to a state
      population-based cancer registry. METHOD: Using theIndiana State Department of
      Health Cancer Registry, 66,395 breast, colorectal, and lung cancer diagnoses
      recorded duringthe years 2001-2009 were examined for timeliness. Timeliness was
      measured from the date the cancer was diagnosed towhen the data were available at
      the state registry. Differences over time and among the 3 cancer types were
      examined.RESULT: Timeliness of reporting improved since 2003. Mean reporting time
      ranged from 426 days in 2003 to 253 days in2009. We found significant difference
      in reporting time between the 3 cancer types. CONCLUSION: Timeliness of reporting
      hasimproved over time. Advances in health information technologies may have
      contributed to this improvement. However,achieving even more timely reporting for
      research purposes and care intervention may require moving away from
      traditionalreporting methods.

PMID- 29595918
TI  - Dynamic cerebral autoregulation is preserved during isometric handgrip and head
      down tilt in healthy volunteers.
AB  - In healthy humans, cerebral blood flow (CBF) is autoregulated against changes in
      arterial blood pressure. Spontaneous fluctuations in mean arterial pressure (MAP)
      and CBF can be used to assess cerebral autoregulation. We hypothesized that
      dynamic cerebral autoregulation is affected by changes in autonomic activity,
      MAP, and cardiac output (CO) induced by handgrip (HG), head-down tilt (HDT), and
      their combination. In thirteen healthy volunteers, we recorded blood velocity by
      ultrasound in the internal carotid artery (ICA), HR, MAP and CO-estimates from
      continuous finger blood pressure, and end-tidal CO2 . Instantaneous ICA beat
      volume (ICABV, mL) and ICA blood flow (ICABF, mL/min) were calculated. Wavelet
      synchronization index gamma (0-1) was calculated for the pairs: MAP-ICABF, CO
      ICABF and HR-ICABV in the low (0.05-0.15 Hz; LF) and high (0.15-0.4 Hz; HF)
      frequency bands. ICABF did not change between experimental states. MAP and CO
      were increased during HG (+16% and +15%, respectively, P < 0.001) and during HDT
      + HG (+12% and +23%, respectively, P < 0.001). In the LF interval, median gamma
      for the MAP-ICABF pair (baseline: 0.23 [0.12-0.28]) and the CO-ICABF pair
      (baseline: 0.22 [0.15-0.28]) did not change with HG, HDT, or their combination.
      High gamma was observed for the HR-ICABV pair at the respiratory frequency, the
      oscillations in these variables being in inverse phase. The unaltered ICABF and
      the low synchronization between MAP and ICABF in the LF interval suggest intact
      dynamic cerebral autoregulation during HG, HDT, and their combination.

PMID- 29595920
TI  - Linkage of Indiana State Cancer Registry and Indiana Network for Patient Care
      Data.
AB  - BACKGROUND: Large automated electronic health records (EHRs), if brought together
      in a federated data model,have the potential to serve as valuable population
      based tools in studying the patterns and effectiveness of treatment. TheIndiana
      Network for Patient Care (INPC) is a unique federated EHR data repository that
      contains data collected from alarge population across various health care
      settings throughout the state of Indiana. The INPC clinical data
      environmentallows quick access and extraction of information from medical charts.
      The purpose of this project was to evaluate 2 differentmethods of record linkage
      between the Indiana State Cancer Registry (ISCR) and INPC, determine the match
      rate forlinkage between the ISCR and INPC data for patients diagnosed with
      cancer, and to assess the completeness of the ISCRbased on additional validated
      cancer cases identified in the INPC EHRs. METHODS: Deterministic and
      probabilistic algorithmswere applied to link ISCR cases to the INPC. The linkage
      results were validated by manual review and the accuracyassessed with positive
      predictive value (PPV). Medical charts of melanoma and lung cancer cases
      identified in INPC butnot linked to ISCR were manually reviewed to identify true
      incidence cancers missed by the ISCR, from which the completenessof the ISCR was
      estimated for each cancer. RESULTS: Both deterministic and probabilistic
      approaches to linkingISCR and INPC had extremely high PPV (>99%) for identifying
      true matches for the overall cohort and each subcohort. Thecombined match rate
      for melanoma and lung cancer cases identified in the ISCR that matched to any
      patient occurrence inINPC (not by disease) was 85.5% for the complete cohort,
      94.4% for melanoma, and 84.4% for lung cancer. The estimatedcompleteness of
      capture by the ISCR was 84% for melanoma and 98% for lung cancer. Conclusion:
      Cancer registries canbe successfully linked to patients' EHR data from
      institutions participating in a regional health information organization(RHIO)
      with a high match rate. A pragmatic approach to data linkage may apply both
      deterministic and probabilisticapproaches together for the diverse purposes of
      cancer control research. The RHIO has the potential to add value to thestate
      cancer registry through the identification of additional true incident cases, but
      more advanced approaches, such asnatural language processing, are needed.

PMID- 29595921
TI  - Are Benign and Borderline Brain Tumors Underreported?
AB  - BACKGROUND: Primary benign and borderline (BB) brain tumors have been reportable
      since 2004 by population-basedcancer registries in the United States. Because
      these tumors often are diagnosed clinically at nonhospital
      settings,underreporting is a big concern. Despite this, the magnitude and
      geographic variations in underreporting are unknown.The objectives of this study
      are to assess variations in BB brain tumor incidence rate by registry and trend
      in comparisonto malignant brain tumors, as well as to identify the factors
      associated with the completeness of BB brain tumor reporting.METHODS: North
      American Association of Central Cancer Registries (NAACCR) Cancer in North
      America (CINA) Deluxe1995-2012 Analytic File, which included data from 47 US
      population-based cancer registries, was used. Age-adjusted incidencerate and
      average annual percent change (APC) were calculated. Correlation coefficients
      were used to assess the relationshipsbetween incidence rates and clinical
      factors. RESULTS: The overall age-adjusted incidence rate was 14.2 per 100,000for
      BB brain tumors and 6.6 per 100,000 for malignant brain tumors. The age-adjusted
      incidence rates of BB brain tumorsvaried by registry from 9.8 per 100,000 to 19.9
      per 100,000, whereas the variations in malignant brain tumors were muchsmaller
      from 4.1 per 100,000 to 7.7 per 100,000. BB brain tumor cases were more likely
      than malignant brain tumors to bediagnosed through radiography without
      microscopic confirmation or surgery. Overall, the BB brain tumor incidence
      ratesignificantly increased by 2.3% per year from 2004 to 2012. In contrast,
      incidence rates of malignant brain tumors significantlydecreased by 0.9% per year
      in the same period. Higher BB brain tumor incidence rates were significantly
      associatedwith higher proportions of cases without microscopic confirmation or
      surgery. These associations were not observed formalignant brain tumors.
      CONCLUSIONS: Incidence rates of BB brain tumors varied substantially across 47 US
      registries andwere higher than those of malignant brain tumors in the United
      States. The variations in incidence rate of BB brain tumorsmay be largely
      attributable to difference in identifying clinically diagnosed cases. The
      increasing incidence rate of BB braintumors may reflect improved case
      ascertainment rather than a biological trend.Key words:

PMID- 29595922
TI  - Osimertinib in EGFR Mutation-Positive Advanced NSCLC.

PMID- 29595923
TI  - Osimertinib in EGFR Mutation-Positive Advanced NSCLC.

PMID- 29595924
TI  - Osimertinib in EGFR Mutation-Positive Advanced NSCLC.

PMID- 29595925
TI  - Improving Vital Status Data Using Text Searches.
AB  - OBJECTIVE: To identify missed deaths in the New York State Cancer Registry
      database and correct the vital statuscode. METHODS: The SEER*DMS SQL data search
      feature was used to identify cases which were potentially miscoded basedon key
      words in the pathology and remarks text section of the abstract and the vital
      status coded. RESULTS: The SEER*DMSSQL data search feature allowed for miscoded
      vital status cases to be easily identified and corrected in our
      database.CONCLUSIONS:  Improving the quality of the data being used for analysis,
      despite the quantity of changes being made, willin time generate more accurate
      survival statistics for the state of New York.

PMID- 29595926
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29595927
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29595928
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29595937
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29595938
TI  - Contemporary Hormonal Contraception and the Risk of Breast Cancer.

PMID- 29595939
TI  - Growth of the Epidemic of Human Papillomavirus-Related Oropharyngeal Carcinomas
      in Whites in Selected US Metropolitan and Nonmetropolitan Counties, 1992-2013.
AB  - BACKGROUND: Age-standardized incidence rates (ASIRs) for US non-Hispanic whites
      (NHWs) have been increasingsince 1999 for squamous cell carcinomas (SCC) at
      oropharyngeal (OP) anatomic sites strongly associated with humanpapillomavirus
      (HPV), as also reported from certain European countries. ASIRs declined slightly,
      however, from 2000-2006to 2007-2012 in Stockholm County, Sweden (an urban area)
      for SCC of the tonsil (TSCC) but not base of tongue (BTSCC).For the United
      States, this study examined the growth of the epidemic of these cancers in 1992
      2013. METHODS: Using join-pointregression, trends were examined in ASIRs for
      BTSCC and TSCC for NHWs in US metropolitan vs nonmetropolitancounties included in
      a unique Surveillance, Epidemiology, and End Results (SEER) program database
      covering 1992-2013(11 registries). Representativeness of recent trends was
      assessed using a larger SEER database (17 registries) covering only2000-2013.
      RESULTS: ASIRs for NHWs were lower for nonmetropolitan vs metropolitan counties
      in 1992-1996 but rapidlyincreased and converged over time (especially using SEER
      17). There was no decline in rates for TSCC in metropolitancounties, but for
      BTSCC, the increase was smaller in recent vs earlier years. Reporting delay of
      cases diagnosed in recentyears was low in both groups of counties. CONCLUSIONS:
      Findings indicate the need for ongoing surveillance includingadditional US
      registries, and determining if rates in nonmetropolitan counties will surpass
      those in metropolitan counties.The rapid rise in rates in SEER nonmetropolitan
      counties also suggests the need for similar surveillance in countries withlarger
      rural populations.

PMID- 29595940
TI  - Co-Care: A Registry for Individuals at Increased Risk for Colorectal Cancer.
AB  - INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer
      death for both men and women in theUnited States. Several factors can increase
      one's risk of CRC, including a personal or family history of CRC, a diagnosis
      orfamily history of a hereditary colon cancer syndrome, or a diagnosis of chronic
      inflammatory bowel disease. The purposeof this project was to create a colorectal
      cancer registry (Co-Care) for individuals with a personal or family history of
      CRC,and those with disorders of the colon or rectum that are associated with an
      increased risk for developing CRC. Methods:To be eligible for the registry,
      patients either had a personal or family history of CRC, a diagnosis or family
      history ofLynch syndrome, familial adenomatous polyposis, or a diagnosis of
      Crohn's colitis or ulcerative colitis with dysplasia.Participants were recruited
      after seeing their gastroenterologist or genetic counselor, or after undergoing a
      full or partialcolectomy at Mount Sinai Hospital in New York City. Eligible
      patients who agreed to participate were interviewed by amember of the research
      staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A
      total of 224 patientswere enrolled in the registry. Participants are mostly
      white, born in the United States, and married, with a bachelor's orgraduate
      degree, reporting an annual household income of $100,000 or more. The largest
      portion have a family history ofCRC (27.2%), and almost half of participants are
      of Jewish descent (46.2%) and have undergone full or partial colectomy(48.2%).
      More than half of participants have neither received genetic counseling (54.5%)
      nor undergone genetic testing(59.7%). Only 3.6% report that they currently smoke
      cigarettes, and 41.1% consume alcohol at least once per week. Lastly,18.3%,
      10.3%, and 27.7% of participants report that they currently take aspirin, folic
      acid/folate pills or tablets, or calciumpills/tablets, respectively. CONCLUSIONS:
      This registry can improve our understanding of CRC and related diseases, and
      beused to design future interventions related to disease risk, prognosis, and
      prevention of CRC.

PMID- 29595942
TI  - Comparing Cancer Registry Abstracted and Self-Reported Data on Race and
      Ethnicity.
AB  - Data on racial and ethnic subgroups from the National Cancer Institute's
      Surveillance, Epidemiology, End Results(SEER) program and Census Bureau
      population estimates are used to estimate cancer incidence rates. A SEER
      NationalLongitudinal Mortality Study (NLMS) linkage of cancer cases diagnosed
      during 1973-2001 revealed mismatches in raceclassification from these sources
      affecting race-specific cancer incidence and mortality rates, particularly for
      minoritiessuch as American Indians and Alaskan Natives (AIANs). Cancer registries
      obtain demographic data from various sources,including patient intake and
      provider records, administrative databases, and imputation algorithms. The
      primary CensusBureau source for racial/ethnic population denominators is self
      reported survey data. We examined 7,970 SEER-NLMScases diagnosed during 2003-2011
      to update the comparison of patient race/ethnicity in cancer registry and
      populationdata sets. SEER and self-reported data did not agree for 5% of cases.
      The sensitivity of SEER data was better for whites(99%) and non-Hispanics (98%)
      than for multiracial individuals (23%) and all AIANs (40%). Intermediate
      sensitivities wereseen for blacks as well as AIANs in Indian Health Service
      contract health service delivery areas (91%), Asians and PacificIslanders (90%),
      and Hispanics (84%). As the United States becomes more diverse, a need exists to
      align race and ethnicitydata from central cancer registries with population data,
      particularly for minority and multiracial groups. High-qualityregistry data on
      race and ethnicity, collected in a similar way as population estimates, will
      enhance cancer surveillance.

PMID- 29595941
TI  - Lung, Breast, and Prostate Cancer Patients with Unknown Ethnicity in US
      Department of Defense Cancer Registry Data: Comparisons to Patients with Known
      Ethnicity.
AB  - INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer
      death for both men and women in theUnited States. Several factors can increase
      one's risk of CRC, including a personal or family history of CRC, a diagnosis
      orfamily history of a hereditary colon cancer syndrome, or a diagnosis of chronic
      inflammatory bowel disease. The purposeof this project was to create a colorectal
      cancer registry (Co-Care) for individuals with a personal or family history of
      CRC,and those with disorders of the colon or rectum that are associated with an
      increased risk for developing CRC. METHODS:To be eligible for the registry,
      patients either had a personal or family history of CRC, a diagnosis or family
      history ofLynch syndrome, familial adenomatous polyposis, or a diagnosis of
      Crohn's colitis or ulcerative colitis with dysplasia.Participants were recruited
      after seeing their gastroenterologist or genetic counselor, or after undergoing a
      full or partialcolectomy at Mount Sinai Hospital in New York City. Eligible
      patients who agreed to participate were interviewed by amember of the research
      staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A
      total of 224 patientswere enrolled in the registry. Participants are mostly
      white, born in the United States, and married, with a bachelor's orgraduate
      degree, reporting an annual household income of $100,000 or more. The largest
      portion have a family history ofCRC (27.2%), and almost half of participants are
      of Jewish descent (46.2%) and have undergone full or partial colectomy(48.2%).
      More than half of participants have neither received genetic counseling (54.5%)
      nor undergone genetic testing(59.7%). Only 3.6% report that they currently smoke
      cigarettes, and 41.1% consume alcohol at least once per week. Lastly,18.3%,
      10.3%, and 27.7% of participants report that they currently take aspirin, folic
      acid/folate pills or tablets, or calciumpills/tablets, respectively. CONCLUSIONS:
      This registry can improve our understanding of CRC and related diseases, and
      beused to design future interventions related to disease risk, prognosis, and
      prevention of CRC.

PMID- 29595943
TI  - Update from the NAACCR AJCC TNM Edits Task Force: Topography Coding Issue for
      Larynx (C32.0-C32.9).

PMID- 29595944
TI  - An Easier Way to Manage Casefinding.

PMID- 29595945
TI  - Medical Record-Documented TNM Categories and Stage Group: Feasibility of Use for
      Cancer Surveillance.
AB  - BACKGROUND AND OBJECTIVES: In 2016, with the discontinuation of the Collaborative
      Staging system, the cancer surveillancecommunity planned to rely on physician
      assigned TNM stage documented in the medical record. The objectivesof this study
      were to describe how often physician-assigned staging components were documented
      in the medical recordsaccessible to the registrar and to assess the agreement of
      these physician-assigned components with registrar-assignedvalues. METHODS: 
      Medical record documents for 282 routine cases from 5 cancer sites were selected
      from the Surveillance,Epidemiology, and End Results registries. First, the
      documents were evaluated to determine how often they contained theTNM staging
      components. Next, the available components were compared with values assigned by
      a panel of experiencedcancer registrars. The agreement for each type of source
      document was estimated among 100 cases. RESULTS: Overall, thephysician-assigned
      TNM components and stage groups were not often found in the medical record.
      Pathologic T and Nwere found most frequently (65% and 64%, respectively).
      Agreement between physician-assigned and registrar-assignedTNM components varied
      (cT = 57%, cN = 72%, pT = 83%, pN = 89%). For stage group, agreement was better
      when thestage group was documented more than once (clinical, 71%; pathologic,
      67%). Path reports included valid pT and pN in79% and 89% of cases, respectively.
      Oncology consultation notes provided valid cT for 83% of cases. Validity was
      lower forother document sources. CONCLUSIONS: The physician-assigned TNM
      components will rarely be documented in the medicalrecord and available to the
      registrar. Collection of accurate stage information for cancer surveillance
      requires cancer registrarsto review the full medical record and assign the TNM
      components required for stage.

PMID- 29595946
TI  - Surveillance of Tonsillar Cancer Incidence Rates in Minority Groups vs Non
      Hispanic Whites in Large US Metropolitan Areas.
AB  - BACKGROUND: For oropharyngeal (OP) cancers at anatomical sites regarded as
      related to human papillomavirus(HPV), surveillance using population-based cancer
      registries has shown that age-standardized incidence rates are higherin US non
      Hispanic whites (NHWs) vs minority groups. Surveillance in large racially
      ethnically diverse urban areas alsoshould be considered. METHODS: Using the US
      Cancer Statistics database, age-standardized incidence rates per year
      wereobtained for 2003-2013 for carcinomas of the tonsil, the OP site most
      strongly associated with HPV. Data were available forNHWs, non-Hispanic blacks
      (NHBs), and Hispanic whites (HWs) in 20 large metropolitan statistical areas
      (MSAs), and forAsian-Pacific Islanders in 8 of these MSAs. Trends in annual rates
      were examined using join-point regression. RESULTS: Theoverall rate (2003-2013)
      was higher for NHWs vs each minority group in almost all MSAs. Little or no NHW
      NHB differencewas found in 3 MSAs, using abbreviated titles: San Francisco, with
      a relatively high rate for NHBs; San Diego, withhigh rates for both groups; and
      Detroit, with a low rate for NHWs and a high rate for NHBs. For individual MSAs
      withsufficient data for trends in at least 1 minority group, rising rates for
      NHWs diverged from NBHs and HWs in New York,and from NHBs in Chicago but not from
      NHBs in Detroit. For HWs, rates increased statistically significantly in the
      MiamiMSA, vs a smaller increase in the Los Angeles MSA and no increase in the New
      York MSA. CONCLUSIONS: Surveillance ofOP carcinoma incidence by MSA appears
      justified, but should use databases that attempt to collect information on racial
      ethnic subgroups (eg, birthplace and/or ancestry for HWs).

PMID- 29595947
TI  - Unique Fluorescent Imaging Probe for Bacterial Surface Localization and Resistant
      Enzyme Imaging.
AB  - Emergence of antibiotic bacterial resistance has caused serious clinical issues
      worldwide due to increasingly difficult treatment. Development of a specific
      approach for selective visualization of resistant bacteria will be highly
      significant for clinical investigations to promote timely diagnosis and treatment
      of bacterial infections. In this article, we present an effective method that not
      only is able to selectively recognize drug resistant AmpC beta-lactamases enzyme
      but, more importantly, is able to interact with bacterial cell wall components,
      resulting in a desired localization effect on the bacterial surface. A unique and
      specific enzyme-responsive cephalosporin probe (DFD-1) has been developed for the
      selective recognition of resistance bacteria AmpC beta-lactamase, by employing
      fluorescence resonance energy transfer with an "off-on" bioimaging. To achieve
      the desired localization, a lipid-azide conjugate (LA-12) was utilized to
      facilitate its penetration into the bacterial surface, followed by copper-free
      click chemistry. This enables the probe DFD-1 to be anchored onto the cell
      surface. In the presence of AmpC enzymes, the cephalosporin beta-lactam ring on
      DFD-1 will be hydrolyzed, leading to the quencher release, thus generating
      fluorescence for real-time resistant bacterial screening. More importantly, the
      bulky dibenzocyclooctyne group in DFD-1 allowed selective recognition toward the
      AmpC bacterial enzyme instead of its counterpart ( e.g., TEM-1 beta-lactamase).
      Both live cell imaging and cell cytometry assays showed the great selectivity of
      DFD-1 to drug resistant bacterial pathogens containing the AmpC enzyme with
      significant fluorescence enhancement (~67-fold). This probe presented promising
      capability to selectively localize and screen for AmpC resistance bacteria,
      providing great promise for clinical microbiological applications.

PMID- 29595948
TI  - Nanoporous Hydrogels for the Observation of Anthrax Exotoxin Translocation
      Dynamics.
AB  - The ability to observe lethal anthrax exotoxins translocating through size
      constricting nanopores in vitro, combined with detailed sequence and structural
      data, has aided in elucidated mechanisms of exotoxin cell entry and toxicity.
      However, due to limited observations of anthrax exotoxins translocating through
      protective antigen nanopores in vitro and the instability of protective antigen
      functionalized suspended lipid bilayers, questions remain regarding the native
      mechanisms of cell entry. Nanoporous hydrogel membranes offer a robust tool for
      studying protein translocation with ensemble measurements that complement
      conventional single-molecule translocation measurements. Here, we utilize
      nanoporous hydrogel membranes to assess the translocation of full-length anthrax
      lethal and edema factors through nanopores similar in diameter to protective
      antigen translocons. We find that, relative to globular serum and other proteins
      that do not translocate natively through nanopores, anthrax exotoxins demonstrate
      significantly reduced barriers to pore entry. Computed free-energy barriers to
      the unfolding of proteins and the dissociation of macromolecular complexes are
      generally found to coincide with translocation. Finally, a nanopore-blocking
      strategy is developed that utilizes nonspecific synthetic peptide constructs and
      effectively prevents LF translocation within the nanoporous hydrogel.

PMID- 29595949
TI  - Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for
      Enzyme Catalysis.
AB  - The mystery associated with catalysis by what were once regarded as protein black
      boxes, diminished with the X-ray crystallographic determination of the three
      dimensional structures of enzyme-substrate complexes. The report that several
      high-resolution X-ray crystal structures of orotidine 5'-monophosphate
      decarboxylase (OMPDC) failed to provide a consensus mechanism for enzyme
      catalyzed decarboxylation of OMP to form uridine 5'-monophosphate, therefore,
      provoked a flurry of controversy. This controversy was fueled by the enormous
      1023-fold rate acceleration for this enzyme, which had " jolted many biochemists'
      assumptions about the catalytic potential of enzymes." Our studies on the
      mechanism of action of OMPDC provide strong evidence that catalysis by this
      enzyme is not fundamentally different from less proficient catalysts, while
      highlighting important architectural elements that enable a peak level of
      performance. Many enzymes undergo substrate-induced protein conformational
      changes that trap their substrates in solvent occluded protein cages, but the
      conformational change induced by ligand binding to OMPDC is incredibly complex,
      as required to enable the development of 22 kcal/mol of stabilizing binding
      interactions with the phosphodianion and ribosyl substrate fragments of OMP. The
      binding energy from these fragments is utilized to activate OMPDC for catalysis
      of decarboxylation at the orotate fragment of OMP, through the creation of a
      tight, catalytically active, protein cage from the floppy, open, unliganded form
      of OMPDC. Such utilization of binding energy for ligand-driven conformational
      changes provides a general mechanism to obtain specificity in transition state
      binding. The rate enhancement that results from the binding of carbon acid
      substrates to enzymes is partly due to a reduction in the carbon acid p Ka that
      is associated with ligand binding. The binding of UMP to OMPDC results in an
      unusually large >12 unit decrease in the p Ka = 29 for abstraction of the C-6
      substrate hydrogen, due to stabilization of an enzyme-bound vinyl carbanion,
      which is also an intermediate of OMPDC-catalyzed decarboxylation. The protein
      ligand interactions operate to stabilize the vinyl carbanion at the enzyme active
      site compared to aqueous solution, rather than to stabilize the transition state
      for the concerted electrophilic displacement of CO2 by H+ that avoids formation
      of this reaction intermediate. There is evidence that OMPDC induces strain into
      the bound substrate. The interaction between the amide side chain of Gln-215 from
      the phosphodianion gripper loop and the hydroxymethylene side chain of Ser-154
      from the pyrimidine umbrella of ScOMPDC position the amide side chain to interact
      with the phosphodianion of OMP. There are no direct stabilizing interactions
      between dianion gripper protein side chains Gln-215, Tyr-217, and Arg-235 and the
      pyrimidine ring at the decarboxylation transition state. Rather these side chains
      function solely to hold OMPDC in the catalytically active closed conformation.
      The hydrophobic side chains that line the active site of OMPDC in the region of
      the departing CO2 product may function to stabilize the decarboxylation
      transition state by providing hydrophobic solvation of this product.

PMID- 29595950
TI  - Ambiguous Role of Growth-Induced Defects on the Semiconductor-to-Metal
      Characteristics in Epitaxial VO2/TiO2 Thin Films.
AB  - Controlling the semiconductor-to-metal transition temperature in epitaxial VO2
      thin films remains an unresolved question both at the fundamental as well as the
      application level. Within the scope of this work, the effects of growth
      temperature on the structure, chemical composition, interface coherency and
      electrical characteristics of rutile VO2 epitaxial thin films grown on TiO2
      substrates are investigated. It is hereby deduced that the transition temperature
      is lower than the bulk value of 340 K. However, it is found to approach this
      value as a function of increased growth temperature even though it is accompanied
      by a contraction along the V4+-V4+ bond direction, the crystallographic c-axis
      lattice parameter. Additionally, it is demonstrated that films grown at low
      substrate temperatures exhibit a relaxed state and a strongly reduced transition
      temperature. It is suggested that, besides thermal and epitaxial strain, growth
      induced defects may strongly affect the electronic phase transition. The results
      of this work reveal the difficulty in extracting the intrinsic material response
      to strain, when the exact contribution of all strain sources cannot be
      effectively determined. The findings also bear implications on the limitations in
      obtaining the recently predicted novel semi-Dirac point phase in VO2/TiO2
      multilayer structures.

PMID- 29595951
TI  - Amplification of CD20 Cross-Linking in Rituximab-Resistant B-Lymphoma Cells
      Enhances Apoptosis Induction by Drug-Free Macromolecular Therapeutics.
AB  - Although the CD20-targeted monoclonal antibody rituximab (RTX) has revolutionized
      the therapeutic landscape for B-cell malignancy, relapsed and refractory disease
      due to RTX resistance continue to constitute major challenges, illustrating the
      need for better therapies. Here, we apply drug-free macromolecular therapeutics
      (DFMT) that amplifies CD20 cross-linking to enhance apoptosis in RTX-resistant
      cells. Bispecific engager (anti-CD20 Fab' conjugated with oligonucleotide1)
      pretargets CD20 and the deletion of Fc-region minimizes its premature endocytosis
      in resistant cells that rapidly internalize and consume CD20/RTX complexes.
      Second-step delivery of multivalent polymeric effector (linear copolymer
      conjugated with multiple copies of complementary oligonucleotide 2)
      simultaneously hybridizes multiple CD20-bound engagers and strengthens CD20
      ligation. Moreover, the restoration of CD20 expression by the pretreatment of
      cells with a polymer-gemcitabine conjugate, a CD20 expression enhancer, unleashes
      the full potential of DFMT in the CD20-deficient resistant cells. Hence,
      amplification of CD20 cross-linking is achieved by (1) the enhancement of surface
      CD20 accessibility, (2) the increase in CD20 expression, and (3) multimeric CD20
      binding, which ultimately translates into the amplified activation of a wide
      range of innate apoptotic responses. We demonstrated that the altered molecular
      signaling pathway that originally results in RTX resistance could be circumvented
      and compensated by other DFMT-augmented pathways. Of note, our preliminary data
      provide proof-of-concept that CD20 cross-linking amplification emerges as an
      important strategy for overcoming RTX resistance.

PMID- 29595952
TI  - Controllable Synthesis of Gold Nanorod/Conducting Polymer Core/Shell Hybrids
      Toward in Vitro and in Vivo near-Infrared Photothermal Therapy.
AB  - Photothermal therapy (PTT) is a minimally invasive tumor treatment technology,
      and is regarded as a potential anticancer strategy because of its targeted
      destruction and low toxicity. Specifically, near-infrared light-induced PTT has
      attracted intriguing interest because of the high transparency of tissue, blood,
      and water. However, effective PTT generally requires the assistance of
      photothermal agents. Gold nanorods (GNRs) and conducting polymer are often used
      as photothermal materials because of their high absorption efficiency and
      photothermal conversion efficiency. Herein, we combined GNRs with poly( o
      methoxyaniline) (POMA, a polyaniline derivative) to form GNRs/POMA core/shell
      hybrids through the surfactant-assisted chemical oxidative polymerization route
      and studied their photothermal conversion properties. The configuration of
      GNRs/POMA core/shell hybrids has been precisely controlled through adjusting the
      monomer concentration, and the relationship between morphology and absorption
      band of GNRs/POMA core/shell hybrids has been revealed. Finally, the in vitro and
      in vivo experiments were performed, and the results indicated that the GNRs/POMA
      core/shell hybrids with optimized absorbance at around 808 nm exhibited the best
      performance on photothermal therapy under 808 nm NIR laser irradiation.

PMID- 29595953
TI  - Ion-Transport Design for High-Performance Na+-Based Electrochromics.
AB  - Sodium ion (Na+)-based electrochemical systems have been extensively investigated
      in batteries and supercapacitors and also can be quality candidates for
      electrochromic (EC) devices. However, poor diffusion kinetics and severe EC
      performance degradation occur during the intercalation/deintercalation processes
      because the ionic radii of Na+ are larger than those of conventional
      intercalation ions. Here, through intentional design of ion-transport channels in
      metal-organic frameworks (MOFs), Na+ serves as an efficient intercalation ion for
      incorporation into a nanostructured electrode with a high diffusion coefficient
      of approximately 10-8 cm2 s-1. As a result, the well-designed MOF-based EC device
      demonstrates desirable Na+ EC performance, including fast switching speed,
      multicolor switching, and high stability. A smart "quick response code" display
      is fabricated using a mask-free laser writing method for application in the
      "Internet of Things". In addition, the concept of ion transport pathway design
      can be widely adopted for fabricating high-performance ion intercalation
      materials and devices for consumer electronics.

PMID- 29595955
TI  - Peptidoglycan Modification by the Catalytic Domain of Streptococcus pneumoniae
      OatA Follows a Ping-Pong Bi-Bi Mechanism of Action.
AB  - Streptococcus pneumoniae among other Gram-positive pathogens produces O
      acetylated peptidoglycan using the enzyme OatA. This process occurs through the
      transfer of an acetyl group from a donor to the hydroxyl group of an acceptor
      sugar. While it has been established that this process involves the
      extracellular, catalytic domain of OatA ( SpOatAC), mechanistic insight is still
      unavailable. This study examined the enzymatic characteristics of SpOatAC
      catalyzed reactions through analysis of both pre-steady- and steady-state
      kinetics. Our findings clearly show that SpOatAC follows a ping-pong bi-bi
      mechanism of action involving a covalent acetyl-enzyme intermediate. The modified
      residue was verified to be the catalytic nucleophile, Ser438. The pH dependence
      of the enzyme kinetics revealed that a single ionizable group is involved, which
      is consistent with the participation of a His residue. Single-turnover kinetics
      of esterase activity demonstrated that k2 ? k3, revealing that the rate-limiting
      step for the hydrolytic reaction was the breakdown of the acetyl-enzyme
      intermediate with a half-life of >1 min. The previous assignment of Asn491 as an
      oxyanion hole residue was also confirmed as its replacement with Ala resulted in
      a 50-fold decrease in catalytic efficiency relative to that of wild-type SpOatAC.
      However, this loss of catalytic efficiency was mostly due to a large increase in
      KM, suggesting that Asn491 contributes more to substrate binding.

PMID- 29595954
TI  - MxiN Differentially Regulates Monomeric and Oligomeric Species of the Shigella
      Type Three Secretion System ATPase Spa47.
AB  - Shigella rely entirely on the action of a single type three secretion system
      (T3SS) to support cellular invasion of colonic epithelial cells and to circumvent
      host immune responses. The ATPase Spa47 resides at the base of the Shigella
      needle-like type three secretion apparatus (T3SA), supporting protein secretion
      through the apparatus and providing a likely means for native virulence
      regulation by Shigella and a much needed target for non-antibiotic therapeutics
      to treat Shigella infections. Here, we show that MxiN is a differential regulator
      of Spa47 and that its regulatory impact is determined by the oligomeric state of
      the Spa47 ATPase, with which it interacts. In vitro and in vivo characterization
      shows that interaction of MxiN with Spa47 requires the six N-terminal residues of
      Spa47 that are also necessary for stable Spa47 oligomer formation and activation.
      This interaction with MxiN negatively influences the activity of Spa47 oligomers
      while upregulating the ATPase activity of monomeric Spa47. Detailed kinetic
      analyses of monomeric and oligomeric Spa47 in the presence and absence of MxiN
      uncover additional mechanistic insights into the regulation of Spa47 by MxiN,
      suggesting that the MxiN/Spa47 species resulting from interaction with monomeric
      and oligomeric Spa47 are functionally distinct and that both could be involved in
      Shigella T3SS regulation. Uncovering regulation of Spa47 by MxiN addresses an
      important gap in the current understanding of how Shigella controls T3SA activity
      and provides the first description of differential T3SS ATPase regulation by a
      native T3SS protein.

PMID- 29595957
TI  - Kinetics and Product Formation during the Photooxidation of Butanol on
      Atmospheric Mineral Dust.
AB  - Mineral dust particles have photochemical properties that can promote
      heterogeneous reactions on their surfaces and therefore alter atmospheric
      composition. Even though dust photocatalytic nature has received significant
      attention recently, most studies have focused on inorganic trace gases. Here, we
      investigated how light changes the chemical interactions between butanol and
      Arizona test dust, a proxy for mineral dust, under atmospheric conditions.
      Butanol uptake kinetics were measured, exploring the effects of UV light
      irradiation intensity (0-1.4 mW/cm2), relative humidity (0-10%), temperature (283
      298 K), and butanol initial concentration (20-55 ppb). The composition of the gas
      phase was monitored by a high-resolution proton-transfer-reaction mass
      spectrometer (PTR-ToF-MS) operating in H3O+ mode. Water was observed to play a
      significant role, initially reducing heterogeneous processing of butanol but
      enhancing reaction rates once it evaporated. Gas phase products were identified,
      showing that surface reactions of adsorbed butanol led to the emission of a
      variety of carbonyl containing compounds. Under actinic light these compounds
      will photolyze and produce hydroxyl radicals, changing dust processing from a
      sink of VOC into a source of reactive compounds.

PMID- 29595956
TI  - Quadruple H-Bonding Cross-Linked Supramolecular Polymeric Materials as Substrates
      for Stretchable, Antitearing, and Self-Healable Thin Film Electrodes.
AB  - Herein, we report a de novo chemical design of supramolecular polymer materials
      (SPMs-1-3) by condensation polymerization, consisting of (i) soft polymeric
      chains (polytetramethylene glycol and tetraethylene glycol) and (ii) strong and
      reversible quadruple H-bonding cross-linkers (from 0 to 30 mol %). The former
      contributes to the formation of the soft domain of the SPMs, and the latter
      furnishes the SPMs with desirable mechanical properties, thereby producing soft,
      stretchable, yet tough elastomers. The resulting SPM-2 was observed to be highly
      stretchable (up to 17 000% strain), tough (fracture energy ~30 000 J/m2), and
      self-healing, which are highly desirable properties and are superior to
      previously reported elastomers and tough hydrogels. Furthermore, a gold, thin
      film electrode deposited on this SPM substrate retains its conductivity and
      combines high stretchability (~400%), fracture/notch insensitivity, self-healing,
      and good interfacial adhesion with the gold film. Again, these properties are all
      highly complementary to commonly used polydimethylsiloxane-based thin film metal
      electrodes. Last, we proceed to demonstrate the practical utility of our
      fabricated electrode via both in vivo and in vitro measurements of
      electromyography signals. This fundamental understanding obtained from the
      investigation of these SPMs will facilitate the progress of intelligent soft
      materials and flexible electronics.

PMID- 29595958
TI  - Modeling Microalgae Productivity in Industrial-Scale Vertical Flat Panel
      Photobioreactors.
AB  - Potentially achievable biomass yields are a decisive performance indicator for
      the economic viability of mass cultivation of microalgae. In this study, a
      computer model has been developed and applied to estimate the productivity of
      microalgae for large-scale outdoor cultivation in vertical flat panel
      photobioreactors. Algae growth is determined based on simulations of the reactor
      temperature and light distribution. Site-specific weather and irradiation data
      are used for annual yield estimations in six climate zones. Shading and
      reflections between opposing panels and between panels and the ground are
      dynamically computed based on the reactor geometry and the position of the sun.
      The results indicate that thin panels (<=0.05 m) are best suited for the assumed
      cell density of 2 g L-1 and that reactor panels should face in north-south
      direction. Panel spacings of 0.4-0.75 m at a panel height of 1 m appear most
      suitable for commercial applications. Under these preconditions, yields of around
      10 kg m-2 a-1 are possible for most locations in the U.S. Only in hot climates
      significantly lower yields have to be expected, as extreme reactor temperatures
      limit overall productivity.

PMID- 29595959
TI  - Zeolite-Templated Mesoporous Silicon Particles for Advanced Lithium-Ion Battery
      Anodes.
AB  - For the practical use of high-capacity silicon anodes in high-energy lithium
      based batteries, key issues arising from the large volume change of silicon
      during cycling must be addressed by the facile structural design of silicon.
      Herein, we discuss the zeolite-templated magnesiothermic reduction synthesis of
      mesoporous silicon (mpSi) (mpSi-Y, -B, and -Z derived from commercial zeolite Y,
      Beta, and ZSM-5, respectively) microparticles having large pore volume (0.4-0.5
      cm3/g), wide open pore size (19-31 nm), and small primary silicon particles (20
      35 nm). With these appealing mpSi particle structural features, a series of
      mpSi/C composites exhibit outstanding performance including excellent cycling
      stabilities for 500 cycles, high specific and volumetric capacities (1100-1700
      mAh g-1 and 640-1000 mAh cm-3 at 100 mA g-1), high Coulombic efficiencies
      (approximately 100%), and remarkable rate capabilities, whereas conventional
      silicon nanoparticles (SiNP)/C demonstrate limited cycle life. These enhanced
      electrochemical responses of mpSi/C composites are further manifested by low
      impedance build-up, high Li ion diffusion rate, and small electrode thickness
      changes after cycling compared with those of SiNP/C composite. In addition to the
      outstanding electrochemical properties, the low-cost materials and high-yield
      processing make the mpSi/C composites attractive candidates for high-performance
      and high-energy Li-ion battery anodes.

PMID- 29595960
TI  - Life and Work of Stress Granules and Processing Bodies: New Insights into Their
      Formation and Function.
AB  - The dynamic formation of stress granules (SGs), processing bodies (PBs), and
      related RNA organelles regulates diverse cellular processes, including the
      coordination of functionally connected messengers, the translational regulation
      at the synapse, and the control of viruses and retrotransposons. Recent studies
      have shown that pyruvate kinase and other enzymes localize in SGs and PBs, where
      they become protected from stress insults. These observations may have
      implications for enzyme regulation and metabolic control exerted by RNA-based
      organelles. The formation of these cellular bodies is governed by liquid-liquid
      phase separation (LLPS) processes, and it needs to be strictly controlled to
      prevent pathogenic aggregation. The intracellular concentration of key
      metabolites, such as ATP and sterol derivatives, may influence protein
      solubility, thus affecting the dynamics of liquid organelles. LLPS in vitro
      depends on the thermal diffusion of macromolecules, which is limited inside
      cells, where the condensation and dissolution of membrane-less organelles are
      helped by energy-driven processes. The active transport by the retrograde motor
      dynein helps SG assembly, whereas the anterograde motor kinesin mediates SG
      dissolution; a tug of war between these two molecular motors allows transient SG
      formation. There is evidence that the efficiency of dynein-mediated transport
      increases with the number of motor molecules associated with the cargo. The
      dynein-dependent transport may be influenced by cargo size as larger cargos can
      load a larger number of motors. We propose a model based on this emergent
      property of dynein motors, which would be collectively stronger during SG
      condensation and weaker during SG breakdown, thus allowing kinesin-mediated
      dispersion.

PMID- 29595961
TI  - Solvatomechanical Bending of Organic Charge Transfer Cocrystal.
AB  - We report here a new ternary solvated (perylene-TCNB).2THF cocrystal, which can
      transform into binary perylene-TCNB cocrystal reversibly by successive desorption
      or absorption of THF solvent. As a consequence, macroscopic mechanical bending
      would be realized when repeated stimulation with THF solvent. The present results
      clearly demonstrated that solvent induced mechanical bending is driven by
      structural change at the molecular scale. Such solvatomechanical bending behavior
      is clearly revealed for the first time.

PMID- 29595962
TI  - Cross-Platform Cancer Cell Identification Using Telomerase-Specific Spherical
      Nucleic Acids.
AB  - Distinguishing tumor cells from normal cells holds the key to precision diagnosis
      and effective intervention of cancers. The fundamental difficulties, however, are
      the heterogeneity of tumor cells and the lack of truly specific and ideally
      universal cancer biomarkers. Here, we report a concept of tumor cell detection,
      bypassing the specific genotypic and phenotypic features of different tumor cell
      types and directly going toward the hallmark of cancer, uncontrollable growth.
      Combining spherical nucleic acids (SNAs) with exquisitely engineered molecular
      beacons (SNA beacons, dubbed SNAB technology) is capable of identifying tumor
      cells from normal cells based on the molecular phenotype of telomerase activity,
      largely bypassing the heterogeneity problem of cancers. Owing to the cell-entry
      capability of SNAs, the SNAB probe readily achieves tumor cell detection across
      multiple platforms, ranging from solution-based assay, to single cell imaging and
      in vivo solid tumor imaging (unlike PCR that is restricted to cell lysates). We
      envision the SNAB technology will impact cancer diagnosis, therapeutic response
      assessment, and image-guided surgery.

PMID- 29595963
TI  - Self-Powered Wind Sensor System for Detecting Wind Speed and Direction Based on a
      Triboelectric Nanogenerator.
AB  - The development of the Internet of Things has brought new challenges to the
      corresponding distributed sensor systems. Self-powered sensors that can perceive
      and respond to environmental stimuli without an external power supply are highly
      desirable. In this paper, a self-powered wind sensor system based on an
      anemometer triboelectric nanogenerator (a-TENG, free-standing mode) and a wind
      vane triboelectric nanogenerator (v-TENG, single-electrode mode) is proposed for
      simultaneously detecting wind speed and direction. A soft friction mode is
      adopted instead of a typical rigid friction for largely enhancing the output
      performance of the TENG. The design parameters including size, unit central
      angle, and applied materials are optimized to enhance sensitivity, resolution,
      and wide measurement scale. The optimized a-TENG could deliver an open-circuit
      voltage of 88 V and short-circuit current of 6.3 MUA, corresponding to a maximum
      power output of 0.47 mW (wind speed of 6.0 m/s), which is capable of driving
      electronics for data transmission and storage. The current peak value of the a
      TENG signal is used for analyzing wind speed for less energy consumption.
      Moreover, the output characteristics of a v-TENG are further explored, with six
      actual operation situations, and the v-TENG delivers fast response to the
      incoming wind and accurately outputs the wind direction data. As a wind sensor
      system, wind speed ranging from 2.7 to 8.0 m/s can be well detected (consistent
      with a commercial sensor) and eight regular directions can be monitored.
      Therefore, the fabricated wind sensor system has great potential in wireless
      environmental monitoring applications.

PMID- 29595964
TI  - In Situ Cellular Glycan Analysis.
AB  - Glycan decorates all mammalian cell surfaces through glycosylation, which is one
      of the most important post-modifications of proteins. Glycans mediate a wide
      variety of biological processes, including cell growth and differentiation, cell
      cell communication, immune response, pathogen interaction, and intracellular
      signaling events. Besides, tumor cells aberrantly express distinct sets of
      glycans, which can indicate different tumor onsets and progression processes.
      Thus, analysis of cellular glycans may contribute to understanding of glycan
      related biological processes and correlation of glycan patterns with disease
      states for clinical diagnosis and treatment. Although proteomics and glycomics
      have included great efforts for in vitro study of glycan structures and functions
      using lysis samples of cells or tissues, they cannot offer real-time qualitative
      or quantitative information, especially spatial distribution, of glycans on/in
      intact cells, which is important to the revelation of glycan-related biological
      events. Moreover, the complex lysis and separation procedures may bring
      unpredictable loss of glycan information. Focusing on the great urgency for in
      situ analysis of cellular glycans, our group developed a series of methods for in
      situ analysis of cellular glycans in the past 10 years. By construction of
      electrochemical glycan-recognizable probes, glycans on the cell surface can be
      quantified by direct or competitive electrochemical detection. Using multichannel
      electrodes or encoded lectin probes, multiple glycans on the cell surface can be
      dynamically monitored simultaneously. Through design of functional nanoprobes,
      the cell surface protein-specific glycans and intracellular glycan-related
      enzymes can be visualized by fluorescence or Raman imaging. Besides, some
      biological enzymes-based methods have been developed for remodeling or imaging of
      protein-specific glycans and other types of glycoconjugates, such as
      gangliosides. Through tracing the changes of glycan expression induced by drugs
      or gene interference, some glycan-related biological processes have been deduced
      or proved, demonstrating the reliability and practicability of the developed
      methods. This Account surveys the key technologies developed in this area, along
      with the discussion on the shortages of current methodology as well as the
      possible strategies to overcome those shortages. The future trend in this topic
      is also discussed. It is expected that this Account can provide a versatile
      arsenal for chemical and biological researchers to unravel the complex mechanisms
      involved in glycan-related biological processes and light new beacons in tumor
      diagnosis and treatment.

PMID- 29595966
TI  - Exploiting Charge-Transfer States for Maximizing Intersystem Crossing Yields in
      Organic Photoredox Catalysts.
AB  - A key feature of prominent transition-metal-containing photoredox catalysts (PCs)
      is high quantum yield access to long-lived excited states characterized by a
      change in spin multiplicity. For organic PCs, challenges emerge for promoting
      excited-state intersystem crossing (ISC), particularly when potent excited-state
      reductants are desired. Herein, we report a design exploiting orthogonal pi
      systems and an intermediate-energy charge-transfer excited state to maximize ISC
      yields (PhiISC) in a highly reducing ( E0* = -1.7 V vs SCE), visible-light
      absorbing phenoxazine-based PC. Simple substitution of N-phenyl for N-naphthyl is
      shown to dramatically increase PhiISC from 0.11 to 0.91 without altering
      catalytically important properties, such as E0*.

PMID- 29595965
TI  - Engineering an [FeFe]-Hydrogenase: Do Accessory Clusters Influence O2 Resistance
      and Catalytic Bias?
AB  - [FeFe]-hydrogenases, HydAs, are unique biocatalysts for proton reduction to H2.
      However, they suffer from a number of drawbacks for biotechnological
      applications: size, number and diversity of metal cofactors, oxygen sensitivity.
      Here we show that HydA from Megasphaera elsdenii (MeHydA) displays significant
      resistance to O2. Furthermore, we produced a shorter version of this enzyme (MeH
      HydA), lacking the N-terminal domain harboring the accessory FeS clusters. As
      shown by detailed spectroscopic and biochemical characterization, MeH-HydA
      displays the following interesting properties. First, a functional active site
      can be assembled in MeH-HydA in vitro, providing the enzyme with excellent
      hydrogenase activity. Second, the resistance of MeHydA to O2 is conserved in MeH
      HydA. Third, MeH-HydA is more biased toward proton reduction than MeHydA, as the
      result of the truncation changing the rate limiting steps in catalysis. This work
      shows that it is possible to engineer HydA to generate an active hydrogenase that
      combines the resistance of the most resistant HydAs and the simplicity of algal
      HydAs, containing only the H-cluster.

PMID- 29595967
TI  - Microgel-in-Microgel Biopolymer Delivery Systems: Controlled Digestion of
      Encapsulated Lipid Droplets under Simulated Gastrointestinal Conditions.
AB  - Structural design principles are increasingly being used to develop colloidal
      delivery systems for bioactive agents. In this study, oil droplets were
      encapsulated within microgel-in-microgel systems. Initially, a nanoemulsion was
      formed that contained small whey protein-coated oil droplets ( d43 = 211 nm).
      These oil droplets were then loaded into either carrageenan-in-alginate (O/MC/MA)
      or alginate-in-carrageenan (O/MA/MC) microgels. A vibrating nozzle encapsulation
      unit was used to form the smaller inner microgels ( d43 = 170-324 MUm), while a
      hand-held syringe was used to form the larger outer microgels ( d43 = 2200-3400
      MUm). Calcium alginate microgels (O/MA) were more stable to simulated
      gastrointestinal tract (GIT) conditions than potassium carrageenan microgels
      (O/MC), which was attributed to the stronger cross-links formed by divalent
      calcium ions than the monovalent potassium ions. As a result, the microgel-in
      microgel systems had different gastrointestinal fates depending upon the nature
      of the external microgel phase; i.e., the O/MC/MA system was more resistant to
      rupture than the O/MA/MC system. The rate of lipid digestion under simulated
      small intestine conditions decreased in the following order: free oil droplets >
      O/MC > O/MA > O/MA/MC > O/MC/MA. This effect was attributed to differences in the
      integrity and dimensions of the microgels in the small intestine, because a
      hydrogel network surrounding the oil droplets inhibits lipid hydrolysis by
      lipase. The structured microgels developed in this study may have interesting
      applications for the protection or controlled release of bioactive agents.

PMID- 29595968
TI  - C-Glycosidation of Unprotected Di- and Trisaccharide Aldopyranoses with Ketones
      Using Pyrrolidine-Boric Acid Catalysis.
AB  - C-Glycoside derivatives are found in pharmaceuticals, glycoconjugates, probes,
      and other functional molecules. Thus, C-glycosidation of unprotected
      carbohydrates is of interest. Here the development of C-glycosidation reactions
      of unprotected di- and trisaccharide aldopyranoses with various ketones is
      reported. The reactions were performed using catalyst systems composed of
      pyrrolidine and boric acid under mild conditions. Carbohydrates used for the C
      glycosidation included lactose, maltose, cellobiose, 3'-sialyllactose, 6'
      sialyllactose, and maltotriose. Using ketones with functional groups, C
      glycosides ketones bearing the functional groups were obtained. The pyrolidine
      boric acid catalysis conditions did not alter the stereochemistry of non-C-C bond
      formation positions of the carbohydrates and led to the formation of the C
      glycosidation products with high diastereoselectivity. For the C-glycosidation of
      the carbohydrates under the pyrrolidine-boric acid-catalysis, the hydroxy group
      at the 6-position of the reacting aldopyranose was necessary to afford the
      product. Our analyses suggest that the carbohydrates form iminium ions with
      pyrrolidine and that boric acid forms B-O covalent bonds with the carbohydrates
      during the catalysis to forward the C-C bond formation.

PMID- 29595969
TI  - Proline Restricts Loop I Conformation of the High Affinity WW Domain from Human
      Nedd4-1 to a Ligand Binding-Competent Type I beta-Turn.
AB  - Sequence alignment of the four WW domains from human Nedd4-1 (neuronal precursor
      cell expressed developmentally down-regulated gene 4-1) reveals that the highest
      sequence diversity exists in loop I. Three residues in this type I beta-turn
      interact with the PPxY motif of the human epithelial Na+ channel (hENaC)
      subunits, indicating that peptide affinity is defined by the loop I sequence. The
      third WW domain (WW3*) has the highest ligand affinity and unlike the other three
      hNedd4-1 WW domains or other WW domains studied contains the highly statistically
      preferred proline at the ( i + 1) position found in beta-turns. In this report,
      molecular dynamics simulations and experimental data were combined to
      characterize loop I stability and dynamics. Exchange of the proline to the
      equivalent residue in WW4 (Thr) results in the presence of a predominantly open
      seven residue Omega loop rather than the type I beta-turn conformation for the
      wild-type apo-WW3*. In the presence of the ligand, the structure of the mutated
      loop I is locked into a type I beta-turn. Thus, proline in loop I ensures a
      stable peptide binding-competent beta-turn conformation, indicating that amino
      acid sequence modulates local flexibility to tune binding preferences and
      stability of dynamic interaction motifs.

PMID- 29595970
TI  - Enantioselective Organocatalytic Sulfenylation of beta-Naphthols.
AB  - An enantioselective sulfenylation of beta-naphthols has been developed for the
      first time using a newly synthesized cinchona-derived thiourea as the catalyst
      and N-(arylthio) succinimide (or phthalimide) as an electrophilic sulfur source.
      Various enantioenriched naphthalenones with an S-containing all-substituted
      stereocenter were prepared via a dearomatization strategy under mild reaction
      conditions.

PMID- 29595971
TI  - Stabilization and Rheology of Concentrated Emulsions Using the Natural
      Emulsifiers Quillaja Saponins and Rhamnolipids.
AB  - Concentrated emulsions are widely used in the cosmetic, personal-care, and food
      industries to reduce storage and transportation costs and to provide desirable
      characteristics. The current study aimed to produce concentrated emulsions (50 wt
      % oil) using two natural emulsifiers, quillaja saponins and rhamnolipids. The
      impacts of emulsifier concentrations on the particle sizes, rheological
      properties, and stabilities of concentrated emulsions were evaluated. Emulsion
      particle sizes were negatively correlated with the concentrations of both
      quillaja saponins and rhamnolipids, and rhamnolipids were more effective in
      producing smaller droplets. Both emulsifiers formed stable concentrated emulsions
      against a series of environmental stresses, including various temperatures (30-90
      degrees C), salt concentrations (<=200 mM NaCl), and pHs (pH 5-8). The rheology
      tests suggested that concentrated emulsions stabilized by quillaja saponins or
      rhamnolipids presented shear-thinning behaviors and had relatively low
      consistency coefficients.

PMID- 29595972
TI  - Hepatoprotective Dibenzocyclooctadiene and Tetrahydrobenzocyclooctabenzofuranone
      Lignans from Kadsura longipedunculata.
AB  - Five new dibenzocyclooctadiene lignans, longipedlignans A-E (1-5), five new
      tetrahydrobenzocyclooctabenzofuranones (6-10), and 18 known analogues (11-28)
      were isolated from the roots of Kadsura longipedunculata. Compounds 6-10 are new
      spirobenzofuranoid-dibenzocyclooctadiene-type lignans. Their structures and
      absolute configurations were established using a combination of MS, NMR, and
      electronic circular dichroism data. Spirobenzofuranoids 6 and 15 showed moderate
      hepatoprotective activity against N-acetyl- p-aminophenol-induced toxicity in
      HepG2 cells with cell survival rates at 10 MUM of 52.2% and 50.2%, respectively.

PMID- 29595973
TI  - Calculation of Ligand Dissociation Energies in Large Transition-Metal Complexes.
AB  - The accurate calculation of ligand dissociation (or equivalently, ligand binding)
      energies is crucial for computational coordination chemistry. Despite its
      importance, obtaining accurate ab initio reference data is difficult, and density
      functional methods of uncertain reliability are chosen for feasibility reasons.
      Here, we consider advanced coupled-cluster and multiconfigurational approaches to
      reinvestigate our WCCR10 set of 10 gas-phase ligand dissociation energies [ J.
      Chem. Theory Comput. 2014, 10, 3092]. We assess the potential
      multiconfigurational character of all molecules involved in these reactions with
      a multireference diagnostic [ Mol. Phys. 2017, 115, 2110] in order to determine
      where single-reference coupled-cluster approaches can be applied. For some
      reactions of the WCCR10 set, large deviations of density-functional results
      including semiclassical dispersion corrections from experimental reference data
      had been observed. This puzzling observation deserves special attention here, and
      we tackle the issue (i) by comparing to ab initio data that comprise dispersion
      effects on a rigorous first-principles footing and (ii) by a comparison of
      density-functional approaches that model dispersion interactions in various ways.
      For two reactions, species exhibiting nonnegligible static electron correlation
      were identified. These two reactions represent hard problems for electronic
      structure methods and also for multireference perturbation theories. However,
      most of the ligand dissociation reactions in WCCR10 do not exhibit static
      electron correlation effects, and hence, we may choose standard single-reference
      coupled-cluster approaches to compare with density-functional methods. For
      WCCR10, the Minnesota M06-L functional yielded the smallest mean absolute
      deviation of 13.2 kJ mol-1 out of all density functionals considered (PBE, BP86,
      BLYP, TPSS, M06-L, PBE0, B3LYP, TPSSh, and M06-2X) without additional dispersion
      corrections in comparison to the coupled-cluster results, and the PBE0-D3
      functional produced the overall smallest mean absolute deviation of 4.3 kJ mol-1.
      The agreement of density-functional results with coupled-cluster data increases
      significantly upon inclusion of any type of dispersion correction. It is
      important to emphasize that different density-functional schemes available for
      this purpose perform equally well. The coupled-cluster dissociation energies,
      however, deviate from experimental results on average by 30.3 kJ mol-1. Possible
      reasons for these deviations are discussed.

PMID- 29595975
TI  - Coupled Cluster Theory Combined with Reference Interaction Site Model Self
      Consistent Field Explicitly Including Spatial Electron Density Distribution.
AB  - Calculating the geometry and energy of a molecule in a solution is one of the
      most important tasks in chemistry. However, performing an accurate calculation in
      a solution is still a difficult task because the electronic structure and solute
      solvent interactions are required to be accurately evaluated with an efficient
      computational cost. To overcome this difficulty, we proposed the coupled cluster
      with single and double excitations and perturbative triple excitations combined
      with the reference interaction site model (RISM) by employing our fitting
      approach. Our method correctly reproduced the relative stabilities of 1,2,3
      triazole, isonicotinic acid, cytosine, and 6-chloro-2-pyridone in the aqueous
      phase, whereas the dielectric continuum model provided incorrect results for
      isonicotinic acid and 6-chloro-2-pyridone. Our method provided accurate results
      because the RISM captured the local solvation structure, such as hydrogen bonds.

PMID- 29595974
TI  - Pathological Features of Staphylococcus aureus Induced Mastitis in Dairy Cows and
      Isobaric-Tags-for-Relative-and-Absolute-Quantitation Proteomic Analyses.
AB  - In part as a result of the production of an enterotoxin, Staphylococcus aureus is
      a highly infectious pathogen and is a considerable threat to food hygiene and
      safety. Clinical mastitis models were established by S. aureus nipple-tube
      perfusion. The influence of mastitis on the mammary-gland-tissue proteomic
      profile was investigated using isobaric tags for relative and absolute
      quantitation. In this study, healthy and mastitic tissues from different mammary
      gland areas of the same dairy cows were screened, and differentially expressed
      proteins were identified. Bioinformatic analysis identified proteins related to
      the inflammation and immunization of dairy cows. Histology, immunoblotting, and
      immunohistochemical-staining analyses were used to determine the expression of
      PGLYRP1 and PTX3 proteins in the acquired mammary-gland-tissue samples. PGLYRP1
      and PTX3 in mastitic mammary glands may be associated with tissue damage and
      immune responses to late stages of infection. This further contributes to the
      understanding of the molecular theory of the treatment of mastitis caused by S.
      aureus.

PMID- 29595976
TI  - An Inverse Electron Demand Azo-Diels-Alder Reaction of o-Quinone Methides and
      Imino Ethers: Synthesis of Benzocondensed 1,3-Oxazines.
AB  - We have studied the reactions of o-quinone methide precursors with imino ethers.
      The reaction provides a versatile route to substituted 1,3-benzoxazines. The
      proposed reaction mechanism involves the generation of the o-quinone methide
      intermediates, imino-Diels-Alder reaction, and elimination. This cascade process
      is a rare example of the participation of imino ethers as dienophiles.

PMID- 29595978
TI  - Understanding the Mechanism Stabilizing Intermediate Spin States in Fe(II)
      Porphyrin.
AB  - Spin fluctuations in Fe(II)-porphyrins are at the heart of heme-proteins
      functionality. Despite significant progress in porphyrin chemistry, the
      mechanisms that rule spin state stabilization remain elusive. Here, it is
      demonstrated by using multiconfigurational quantum chemical approaches, including
      the novel Stochastic-CASSCF method, that electron delocalization between the
      metal center and the pi system of the macrocycle differentially stabilizes the
      triplet spin states over the quintet. This delocalization takes place via charge
      transfer excitations, involving the pi system of the macrocycle and the out-of
      plane iron d orbitals, key linking orbitals between metal and macrocycle. Through
      a correlated breathing mechanism the 3d electrons can make transitions toward the
      pi orbitals of the macrocycle. This guarantees a strong coupling between the on
      site radial correlation on the metal and electron delocalization. Opposite-spin
      3d electrons of the triplet can effectively reduce electron repulsion in this
      manner. Constraining the out-of-plane orbitals from breathing hinders
      delocalization and reverses the spin ordering. The breathing mechanism is made
      effective by strong electron correlation effects in the pi system of the
      macrocycle. Reducing the correlation treatment on the macrocycle to second-order
      only also reverses the spin ordering. High order (beyond second-order)
      correlation on the macrocycle reduces the energetic cost of the additional
      electron to a sufficient extent to stabilize the triplet state. Our results find
      a qualitative analogue in six resonance structures involving the metal center in
      the Fe2+ and Fe3+ oxidation states.

PMID- 29595977
TI  - Trehalose Mediated Inhibition of Lactate Dehydrogenase from Rabbit Muscle. The
      Application of Kramers' Theory in Enzyme Catalysis.
AB  - Lactate dehydrogenase (LDH) catalyzes the reduction of pyruvate to lactate by
      using NADH. LDH kinetics has been proposed to be dependent on the dynamics of a
      loop over the active site. Kramers' theory has been useful in the study of enzyme
      catalysis dependent on large structural dynamics. In this work, LDH kinetics was
      studied in the presence of trehalose and at different temperatures. In the
      absence of trehalose, temperature increase raised exponentially the LDH Vmax and
      revealed a sigmoid transition of Km toward a low-affinity state similar to
      protein unfolding. Notably, LDH Vmax diminished when in the presence of
      trehalose, while pyruvate affinity increased and the temperature-mediated binding
      site transition was hindered. The effect of trehalose on kcat was viscosity
      dependent as described by Kramers' theory since Vmax correlated inversely with
      the viscosity of the medium. As a result, activation energy ( Ea) for pyruvate
      reduction was dramatically increased by trehalose presence. This work provides
      experimental evidence that the dynamics of a structural component in LDH is
      essential for catalysis, i.e., the closing of the loop on the active site. While
      the trehalose mediated-increased of pyruvate affinity is proposed to be due to
      the compaction and/or increase of structural order at the binding site.

PMID- 29595979
TI  - Spatial and Spin Symmetry Breaking in Semidefinite-Programming-Based Hartree-Fock
      Theory.
AB  - The Hartree-Fock problem was recently recast as a semidefinite optimization over
      the space of rank-constrained two-body reduced-density matrices (RDMs) [ Phys.
      Rev. A 2014 , 89 , 010502(R) ]. This formulation of the problem transfers the
      nonconvexity of the Hartree-Fock energy functional to the rank constraint on the
      two-body RDM. We consider an equivalent optimization over the space of positive
      semidefinite one-electron RDMs (1-RDMs) that retains the nonconvexity of the
      Hartree-Fock energy expression. The optimized 1-RDM satisfies ensemble N
      representability conditions, and ensemble spin-state conditions may be imposed as
      well. The spin-state conditions place additional linear and nonlinear constraints
      on the 1-RDM. We apply this RDM-based approach to several molecular systems and
      explore its spatial (point group) and spin ( S2 and S3) symmetry breaking
      properties. When imposing S2 and S3 symmetry but relaxing point group symmetry,
      the procedure often locates spatial-symmetry-broken solutions that are difficult
      to identify using standard algorithms. For example, the RDM-based approach yields
      a smooth, spatial-symmetry-broken potential energy curve for the well-known Be-H2
      insertion pathway. We also demonstrate numerically that, upon relaxation of S2
      and S3 symmetry constraints, the RDM-based approach is equivalent to real-valued
      generalized Hartree-Fock theory.

PMID- 29595980
TI  - Time-Resolved In Situ Liquid-Phase Atomic Force Microscopy and Infrared
      Nanospectroscopy during the Formation of Metal-Organic Framework Thin Films.
AB  - Metal-organic framework (MOF) thin films show unmatched promise as smart
      membranes and photocatalytic coatings. However, their nucleation and growth
      resulting from intricate molecular assembly processes are not well understood yet
      are crucial to control the thin film properties. Here, we directly observe the
      nucleation and growth behavior of HKUST-1 thin films by real-time in situ AFM at
      different temperatures in a Cu-BTC solution. In combination with ex situ infrared
      (nano)spectroscopy, synthesis at 25  degrees C reveals initial nucleation of
      rapidly growing HKUST-1 islands surrounded by a continuously nucleating but
      slowly growing HKUST-1 carpet. Monitoring at 13 and 50  degrees C shows the
      strong impact of temperature on thin film formation, resulting in (partial)
      nucleation and growth inhibition. The nucleation and growth mechanisms as well as
      their kinetics provide insights to aid in future rational design of MOF thin
      films.

PMID- 29595982
TI  - Li Distribution Heterogeneity in Solid Electrolyte Li10GeP2S12 upon
      Electrochemical Cycling Probed by 7Li MRI.
AB  - All-solid-state rechargeable batteries embody the promise for high energy
      density, increased stability, and improved safety. However, their success is
      impeded by high resistance for mass and charge transfer at electrode-electrolyte
      interfaces. Li deficiency has been proposed as a major culprit for interfacial
      resistance, yet experimental evidence is elusive due to the challenges associated
      with noninvasively probing the Li distribution in solid electrolytes. In this
      Letter, three-dimensional 7Li magnetic resonance imaging (MRI) is employed to
      examine Li distribution homogeneity in solid electrolyte Li10GeP2S12 within
      symmetric Li/Li10GeP2S12/Li batteries. 7Li MRI and the derived histograms reveal
      Li depletion from the electrode-electrolyte interfaces and increased
      heterogeneity of Li distribution upon electrochemical cycling. Significant Li
      loss at interfaces is mitigated via facile modification with a poly(ethylene
      oxide)/bis(trifluoromethane)sulfonimide Li salt thin film. This study
      demonstrates a powerful tool for noninvasively monitoring the Li distribution at
      the interfaces and in the bulk of all-solid-state batteries as well as a
      convenient strategy for improving interfacial stability.

PMID- 29595983
TI  - Catalytic Aza-Wacker Annulation: Tuning Mechanism by the Activation Mode of Amide
      and Enantioselective Syntheses of Melinonine-E and Strychnoxanthine.
AB  - An unprecedented N-substituent of the amide was found to be crucial for the
      successful annulation to establish 2-azabicyclo[3.3.1]nonane and other ring
      skeletons in good yield. The novel catalytic aza-Wacker annulation methodology
      was further illustrated in the concise syntheses and the absolute configuration
      determinations of melinonine-E and strychnoxanthine.

PMID- 29595981
TI  - Detergent Desorption of Membrane Proteins Exhibits Two Kinetic Phases.
AB  - Gradual dissociation of detergent molecules from water-insoluble membrane
      proteins culminates in protein aggregation. However, the time-dependent
      trajectory of this process remains ambiguous because the signal-to-noise ratio of
      most spectroscopic and calorimetric techniques is drastically declined by the
      presence of protein aggregates in solution. We show that by using steady-state
      fluorescence polarization (FP) spectroscopy the dissociation of the protein
      detergent complex (PDC) can be inspected in real time at detergent concentrations
      below the critical micelle concentration. This article provides experimental
      evidence of the coexistence of two distinct phases of the dissociations of
      detergent monomers from membrane proteins. We first noted a slow detergent
      predesolvation process, which was accompanied by a relatively modest change in
      the FP anisotropy, suggesting a small number of dissociated detergent monomers
      from the proteomicelles. This predesolvation phase was followed by a fast
      detergent desolvation process, which was highlighted by a major alteration in the
      FP anisotropy. The durations and rates of these phases were dependent on both the
      detergent concentration and the interfacial PDC interactions. Further development
      of this approach might lead to the creation of a new semiquantitative method for
      the assessment of the kinetics of association and dissociation of proteomicelles.

PMID- 29595984
TI  - Exosomes from Irradiated Nonsmall Cell Lung Cancer Cells Reduced Sensitivity of
      Recipient Cells to Anaplastic Lymphoma Kinase Inhibitors.
AB  - Exosomes, released from various cell types, serve as vehicles of intercellular
      communication. Rearranged anaplastic lymphoma kinase (ALK) has been detected in
      exosomes released from cancer cells in ALK-positive nonsmall cell lung cancer
      (NSCLC), however, the functional consequence of ALK in exosomes has not been
      studied. This study aims to address whether exosomal ALK release is affected by
      stress, and whether exosomal ALK can modulate survival of recipient cells in
      vitro and in vivo. Exosomes, isolated from ALK-containing H3122 cells with (Exo
      Apo) or without (Exo-Ctrl) irradiation treatment, were transferred to recipient
      H3122 cells in vitro or mouse xenograft in vivo. Western blot, flow cytometry,
      MTT, and xenograft were employed to respectively assess activation of the ALK
      pathway, apoptosis, cell viability, and tumor growth. Exo-Apo contained much
      higher levels of phosphorylated ALK (p-ALK) than that of Exo-Ctrl, and it
      activated AKT, STAT3, and the ERK pathway in recipient H3122 cells. ALK-specific
      inhibitors, including Crizotinib, Ceritinib, and TAE684, exhibited less effects
      on H3122 cells preincubated with Exo-Apo than on those treated with Exo-Ctrl in
      either inhibition of cell viability or promotion of apoptosis. Moreover, in an
      H3122 xenograft model, the Exo-Apo treatment resulted in a greater tumor growth
      and less sensitivity to Ceritinib than the Exo-Ctrl treatment. The ALK protein
      cargo in exosomes could be a key element to drive tumor growth and compromise
      therapeutic efficacy of ALK inhibitors for ALK-positive NSCLC.

PMID- 29595985
TI  - Phosphonic Acids on an Atomically Defined Oxide Surface: The Binding Motif
      Changes with Surface Coverage.
AB  - We have studied the anchoring mechanism of a phosphonic acid on an atomically
      defined oxide surface. Using time-resolved infrared reflection absorption
      spectroscopy, we investigated the reaction of deuterated phenylphosphonic acid
      (DPPA, C6H5PO3D2) with an atomically defined Co3O4(111) surface in situ during
      film growth by physical vapor deposition. We show that the binding motif of the
      phosphonate anchor group changes as a function of coverage. At low coverage, DPPA
      binds in the form of a chelating tridentate phosphonate, while a transition to a
      chelating bidentate occurs close to monolayer saturation coverage. However, the
      coverage-dependent change in the binding motif is not associated with a major
      change of the molecular orientation, suggesting that the rigid phosphonate linker
      always maintains the DPPA in a strongly tilted orientation irrespective of the
      surface coverage.

PMID- 29595986
TI  - Organocatalytic, Enantioselective Friedel-Crafts Reaction of Indoles in the
      Carbocyclic Ring and Electron-Rich Phenols.
AB  - An efficient method has been successfully developed to achieve the asymmetric C-H
      functionalization of indoles in the carbocyclic ring via organocatalysis, and a
      variety of tetrahydropyranoindoles were synthesized in good yields with excellent
      stereoselectivities. Further study on thermodynamic calculations indicated that
      the process was promoted by generating more thermodynamically stable products.
      This strategy, together with traditional C-3 functionalization of hydroxyindoles,
      could realize the switchable, regiodivergent asymmetric modification of indoles.

PMID- 29595987
TI  - Influence of the Nature of the Alkali Metal Cations on the Electrical Double
      Layer Capacitance of Model Pt(111) and Au(111) Electrodes.
AB  - Understanding the properties of the electrical double layer (EDL) is one of the
      interdisciplinary topics that plays a key role in the investigation of numerous
      natural and artificial systems. We present experimental evidence about the
      influence of the nature of the alkali metal cations on the EDL capacitance for
      two model electrodes, Pt(111) and Au(111), in 0.05 M AMClO4 ( AM: Li+, Na+, K+,
      Rb+, Cs+) electrolytes using impedance spectroscopy measurements. Our data show
      that counterintuitively the differential EDL capacitance of both electrodes
      measured close to their potentials of zero charge increased linearly in the
      presence of alkali metal cations as Li+ < Na+ < K+ < Rb+ < Cs+. We also estimated
      the effective concentrations of these cations at the EDL, which appeared ~80
      times higher than their bulk concentrations. We believe that these findings
      should be of importance for theoretical modeling of the EDL and better
      understanding and faster design of new functional systems for numerous
      applications.

PMID- 29595988
TI  - Observation and Manipulation of Visible Edge Plasmons in Bi2Te3 Nanoplates.
AB  - Noble metals, like Ag and Au, are the most intensively studied plasmonic
      materials in the visible range. Plasmons in semiconductors, however, are usually
      believed to be in the infrared wavelength region due to the intrinsic low carrier
      concentrations. Herein, we observe the edge plasmon modes of Bi2Te3, a narrow
      band gap semiconductor, in the visible spectral range using photoemission
      electron microscopy (PEEM). The Bi2Te3 nanoplates excited by 400 nm femtosecond
      laser pulses exhibit strong photoemission intensities along the edges, which
      follow a cos4 dependence on the polarization state of incident beam. Because of
      the phase retardation effect, plasmonic response along different edges can be
      selectively exited. The thickness-dependent photoemission intensities exclude the
      spin-orbit induced surface states as the origin of these plasmonic modes.
      Instead, we propose that the interband transition-induced nonequilibrium carriers
      might play a key role. Our results not only experimentally demonstrate the
      possibility of visible plasmons in semiconducting materials but also open up a
      new avenue for exploring the optical properties of topological insulator
      materials using PEEM.

PMID- 29595989
TI  - Copper-Catalyzed Annulation Cascades of Alkyne-Tethered alpha-Bromocarbonyls with
      Alkynes: An Access to Heteropolycycles.
AB  - We here describe a new Cu-catalyzed annulation cascade of alkyne-tethered alpha
      bromocarbonyls with common alkynes for the synthesis of various heteropolycycle
      frameworks, including 1 H-benzo[ de]quinolin-2(3 H)-ones, 4 H-dibenzo[
      de,g]quinolin-5(6 H)-one, and benzo[ de]chromen-2(3 H)-one, which were
      constructed with high selectivity. This was achieved by two-component annulation
      cascades, rather than atom-transfer radical cyclization (ATRC), with alkyne
      tethered alpha-bromocarbonyls for one-step accessing heteropolycycles via C-Br
      bond split, intramolecular cyclization, intermolecular [4 + 2] annulation, and
      aryl C(sp2)-H functionalization cascades.

PMID- 29595990
TI  - First-Principles Computed Rate Constant for the O + O2 Isotopic Exchange Reaction
      Now Matches Experiment.
AB  - We show, by performing exact time-independent quantum molecular scattering
      calculations, that the quality of the ground electronic state global potential
      energy surface appears to be of utmost importance in accurately obtaining even as
      strongly averaged quantities as kinetic rate constants. The oxygen isotope
      exchange reaction, 18O + 32O2, motivated by the understanding of a complex long
      standing problem of isotopic ozone anomalies in the stratosphere and laboratory
      experiments, is explored in this context. The thermal rate constant for this key
      reaction is now in quantitative agreement with all experimental data available to
      date. A significant recent progress at the frontier of three research domains,
      advanced electronic structure calculations, ultrasensitive spectroscopy, and
      quantum scattering calculations, has therefore permitted a breakthrough in the
      theoretical modeling of this crucial collision process from first principles.

PMID- 29595992
TI  - Improving Lateral Flow Assay Performance Using Computational Modeling.
AB  - The performance, field utility, and low cost of lateral flow assays (LFAs) have
      driven a tremendous shift in global health care practices by enabling diagnostic
      testing in previously unserved settings. This success has motivated the continued
      improvement of LFAs through increasingly sophisticated materials and reagents.
      However, our mechanistic understanding of the underlying processes that drive the
      informed design of these systems has not received commensurate attention. Here,
      we review the principles underpinning LFAs and the historical evolution of theory
      to predict their performance. As this theory is integrated into computational
      models and becomes testable, the criteria for quantifying performance and
      validating predictive power are critical. The integration of computational design
      with LFA development offers a promising and coherent framework to choose from an
      increasing number of novel materials, techniques, and reagents to deliver the low
      cost, high-fidelity assays of the future.

PMID- 29595991
TI  - The Clinical Effects of Manipulative Therapy in People with Chronic Obstructive
      Pulmonary Disease.
AB  - OBJECTIVES: This study aimed to determine the effects of manipulative therapies
      (MT), including spinal manipulation, and diaphragmatic release techniques on lung
      function, exercise capacity, symptoms, and health-related quality of life (HRQOL)
      in people with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic
      review. PARTICIPANTS: People diagnosed with COPD. INTERVENTION: Randomized
      controlled trials of MT (either with or without pulmonary rehabilitation [PR])
      compared to other treatments (soft tissue [ST] therapy or sham therapy) applied
      in people with COPD were identified following the search of seven databases. Two
      reviewers independently assessed study quality and extracted data. OUTCOME
      MEASURES: Lung function, exercise capacity, symptoms, and HRQOL. RESULTS: Four
      studies were included, with a total of 68 participants. The heterogeneity between
      treatments prevented meta-analysis. There was no beneficial effect on spirometry
      measures of lung function with MT. MT combined with PR improved exercise capacity
      by 48-49 m more than ST therapy plus PR. Less dyspnea was reported with MT and ST
      therapy compared to ST therapy alone (p = 0.01), but there was no effect on
      HRQOL, or symptoms of anxiety or depression. CONCLUSIONS: In people with COPD, MT
      (either with or without PR) improved functional exercise capacity, but had no
      effect on lung function, or HRQOL. Further research is required to determine the
      underlying mechanism of this treatment approach and its relationship to exercise
      capacity.

PMID- 29595993
TI  - Factors Predictive of Healing in Large Rotator Cuff Tears: Is It Possible to
      Predict Retear Preoperatively?
AB  - BACKGROUND: Many studies have identified risk factors that cause retear after
      rotator cuff repair. However, it is still questionable whether retears can be
      predicted preoperatively. PURPOSE: To determine the risk factors related to
      retear after arthroscopic rotator cuff repair and to evaluate whether it is
      possible to predict the occurrence of retear preoperatively. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: This study enrolled 112 patients
      who underwent arthroscopic rotator cuff repair with single-row technique for a
      large-sized tear, defined as a tear with a mediolateral length of 3 to 5 cm. All
      patients underwent routine magnetic resonance imaging (MRI) at 9 months
      postoperatively to assess tendon integrity. The sample included 61 patients
      (54.5%) in the healed group and 51 (45.5%) in the retear group. RESULTS: In
      multivariate analysis, the independent predictors of retears were supraspinatus
      muscle atrophy ( P < .001) and fatty infiltration of the infraspinatus ( P =
      .027), which could be preoperatively measured by MRI. A significant difference
      was found between the two groups in sex, the acromiohumeral interval, tendon
      tension, and preoperative or intraoperative mediolateral tear length and
      musculotendinous junction position in univariate analysis. However, these
      variables were not independent predictors in multivariate analysis. The cutoff
      values of occupation ratio of supraspinatus and fatty infiltration of the
      infraspinatus were 43% and grade 2, respectively. The occupation ratio of
      supraspinatus <43% and grade >=2 fatty infiltration of the infraspinatus were the
      strongest predictors of retear, with an area under the curve of 0.908,
      sensitivity of 98.0%, and specificity of 83.6% (accuracy = 90.2%). CONCLUSION: In
      patients with large rotator cuff tears, it was possible to predict the retear
      before rotator cuff repair regardless of intraoperative factors. The retear could
      be predicted most effectively when the occupation ratio of supraspinatus was <43%
      or the fatty infiltration of infraspinatus was grade >=2. Predicting retear
      preoperatively may help surgeons determine proper treatment and predict the
      postoperative prognosis.

PMID- 29595995
TI  - Barriers and Facilitators of Breastfeeding Reported by Postpartum Women in
      Methadone Maintenance Therapy.
AB  - INTRODUCTION: This study utilized a cross-sectional qualitative and quantitative
      interview-based survey to capture the infant feeding practices and barriers to
      exclusive breastfeeding for women in methadone maintenance therapy. Participants
      were recruited from an opioid dependence treatment center in an urban setting in
      the Southeastern United States. MATERIALS AND METHODS: A convenience sample of
      women in treatment (n = 30) were interviewed using an adapted instrument designed
      to capture decisions and intentions to formula feed or breastfeed; support from
      friends and family; hospital experience; support from healthcare personnel; and
      maternal knowledge of breastfeeding while taking methadone. RESULTS: The majority
      of women in the sample initiated breastfeeding, but only 10% continued for >1
      month. Challenges related to infant hospital stay posed a significant barrier.
      Two-thirds of infants remained hospitalized after the mother was discharged. Out
      of the 24 women who initiated breastfeeding, 11 reported that they discontinued
      because of issues related to infant's neonatal intensive care unit (NICU) stay.
      Eleven women reported that their healthcare providers did not discuss
      breastfeeding with them. Women who were encouraged to breastfeed by healthcare
      staff were more likely to breastfeed for longer durations. CONCLUSIONS: Women in
      treatment for opioid dependence both desire and attempt to establish
      breastfeeding, but encounter significant challenges, including long NICU stays
      and lack of support and education, that compromise their success. These findings
      should inform the development of future programs or interventions geared toward
      increasing breastfeeding initiation, support, and duration among women who give
      birth to babies while in treatment for opioid addiction.

PMID- 29595994
TI  - ABM Clinical Protocol #28, Peripartum Analgesia and Anesthesia for the
      Breastfeeding Mother.
AB  - A central goal of the Academy of Breastfeeding Medicine is the development of
      clinical protocols, free from commercial interest or influence, for managing
      common medical problems that may impact breastfeeding success. These protocols
      serve only as guidelines for the care of breastfeeding mothers and infants and do
      not delineate an exclusive course of treatment or serve as standards of medical
      care. Variations in treatment may be appropriate according to the needs of an
      individual patient.

PMID- 29595996
TI  - Return to Play After Hip Arthroscopy: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: The use of arthroscopic treatment for intra-articular hip pathology
      has demonstrated improved patient-reported outcomes (PROs) with a lower rate of
      complications, reoperation, and patient morbidity as compared with traditional
      methods. Although the use of this minimally invasive approach has increased in
      prevalence, no evidence-based return-to-play (RTP) criteria have been developed
      to ensure an athlete's preparedness for sporting activities. PURPOSE: To
      determine if there exists sufficient evidence in the literature to support an RTP
      protocol and functional assessment after hip arthroscopy, as well as to assess
      the mean rate and duration of RTP. STUDY DESIGN: Systematic review and meta
      analysis. METHODS: The search terms "hip arthroscopy," "return to play," and 10
      related terms were searched in PubMed, Cochrane Library, Scopus, and Web of
      Science, yielding 263 articles. After screening, 22 articles were included. RTP
      timeline, rehabilitation protocols, and conditional criteria measures were
      assessed with previously established criteria. Pooled estimates were calculated
      for RTP rate and duration, and weighted mean scores were determined for PROs.
      RESULTS: A total of 1296 patients with 1442 total hips were identified. Although
      54.5% (12 of 22) of studies did not provide a guideline for RTP duration after
      hip arthroscopy, 36.4% (8 of 22) recommended a duration of 4 months, while 9.1%
      (2 of 22) recommended 3 months. The most frequently described postoperative
      rehabilitation protocols were weightbearing guidelines (15 studies) and passive
      motion exercises (9 studies). Only 2 studies satisfied the criteria for a
      sufficient RTP protocol, and 3 provided a specific replicable test for RTP. The
      mean RTP duration was 7.4 months (95% CI, 6.1-8.8 months), and the return rate
      was 84.6% (95% CI, 80.4%-88.8%; P = .008) at a mean +/- SD follow-up of 25.8 +/-
      2.4 months. Mean modified Harris Hip Score (mHHS) improved from 63.1 to 84.1
      postoperatively (+33.3%), while Non-arthritic Hip Score improved from 61.7 to
      86.8 (+40.7%). A lower preoperative mHHS was significantly associated with a
      higher postoperative improvement ( r = -0.95, P = .0003). CONCLUSION: Significant
      variability exists in RTP protocols among institutions owing to a lack of
      standardization. Despite a high overall rate of RTP and improvement in PROs after
      hip arthroscopy, the majority of rehabilitation protocols are not evidence based
      and rely on expert opinion. No validated functional test currently exists to
      assess RTP.

PMID- 29595998
TI  - Single-Molecule View of Small RNA-Guided Target Search and Recognition.
AB  - Most everyday processes in life involve a necessity for an entity to locate its
      target. On a cellular level, many proteins have to find their target to perform
      their function. From gene-expression regulation to DNA repair to host defense,
      numerous nucleic acid-interacting proteins use distinct target search mechanisms.
      Several proteins achieve that with the help of short RNA strands known as guides.
      This review focuses on single-molecule advances studying the target search and
      recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced
      short palindromic repeats) systems. We discuss different steps involved in search
      and recognition, from the initial complex prearrangement into the target-search
      competent state to the final proofreading steps. We focus on target search
      mechanisms that range from weak interactions, to one- and three-dimensional
      diffusion, to conformational proofreading. We compare the mechanisms of Argonaute
      and CRISPR with a well-studied target search system, RecA.

PMID- 29595999
TI  - Shale Gas Implications for C2-C3 Olefin Production: Incumbent and Future
      Technology.
AB  - Substantial natural gas liquids recovery from tight shale formations has produced
      a significant boon for the US chemical industry. As fracking technology improves,
      shale liquids may represent the same for other geographies. As with any major
      industry disruption, the advent of shale resources permits both the chemical
      industry and the community an excellent opportunity to have open, foundational
      discussions on how both public and private institutions should research, develop,
      and utilize these resources most sustainably. This review summarizes current
      chemical industry processes that use ethane and propane from shale gas liquids to
      produce the two primary chemical olefins of the industry: ethylene and propylene.
      It also discusses simplified techno-economics related to olefins production from
      an industry perspective, attempting to provide a mutually beneficial context in
      which to discuss the next generation of sustainable olefin process development.

PMID- 29596000
TI  - Nanoscale Optical Microscopy and Spectroscopy Using Near-Field Probes.
AB  - Light-matter interactions can provide a wealth of detailed information about the
      structural, electronic, optical, and chemical properties of materials through
      various excitation and scattering processes that occur over different length,
      energy, and timescales. Unfortunately, the wavelike nature of light limits the
      achievable spatial resolution for interrogation and imaging of materials to
      roughly lambda/2 because of diffraction. Scanning near-field optical microscopy
      (SNOM) breaks this diffraction limit by coupling light to nanostructures that are
      specifically designed to manipulate, enhance, and/or extract optical signals from
      very small regions of space. Progress in the SNOM field over the past 30 years
      has led to the development of many methods to optically characterize materials at
      lateral spatial resolutions well below 100 nm. We review these exciting
      developments and demonstrate how SNOM is truly extending optical imaging and
      spectroscopy to the nanoscale.

PMID- 29595997
TI  - Structure and Immune Recognition of the HIV Glycan Shield.
AB  - Vaccine design efforts against the human immunodeficiency virus (HIV) have been
      greatly stimulated by the observation that many infected patients eventually
      develop highly potent broadly neutralizing antibodies (bnAbs). Importantly, these
      bnAbs have evolved to recognize not only the two protein components of the viral
      envelope protein (Env) but also the numerous glycans that form a protective
      barrier on the Env protein. Because Env is heavily glycosylated compared to host
      glycoproteins, the glycans have become targets for the antibody response.
      Therefore, considerable efforts have been made in developing and validating
      biophysical methods to elucidate the complex structure of the Env-spike
      glycoprotein, with its combination of glycan and protein epitopes. We illustrate
      here how the application of robust biophysical methods have transformed our
      understanding of the structure and function of the HIV Env spike and stimulated
      innovation in vaccine design strategies that takes into account the essential
      glycan components Expected final online publication date for the Annual Review of
      Biophysics Volume 47 is May 20, 2018. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 29596001
TI  - Identification of Candidate Genes Involved in the Salt Tolerance of Date Palm
      (Phoenix dactylifera L.) Based on a Yeast Functional Bioassay.
AB  - Although date palm is a relatively salt-tolerant plant, the molecular basis of
      this tolerance is complex and poorly understood. Therefore, this study aimed to
      identify the genes involved in salinity tolerance using a basic yeast functional
      bioassay. To achieve this, a date palm cDNA library was overexpressed in
      Saccharomyces cerevisiae cells. The expression levels of selected genes that make
      yeast cells tolerant to salt were subsequently validated in the leaf and root
      tissues of date palm seedlings using a quantitative PCR method. About 6000 yeast
      transformant cells were replica printed and screened on a synthetic minimal
      medium containing 1.0 M of NaCl. The screening results showed the presence of 62
      salt-tolerant transformant colonies. Sequence analysis of the recombinant yeast
      plasmids revealed the presence of a group of genes with potential salt-tolerance
      functions, such as aquaporins (PIP), serine/threonine protein kinases (STKs),
      ethylene-responsive transcription factor 1 (ERF1), and peroxidases (PRX). The
      expression pattern of the selected genes endorsed the hypothesis that these genes
      may be involved in salinity tolerance, as they showed a significant (p < 0.05)
      overexpression trend in both the leaf and root tissues in response to salinity.
      The genes identified in this project are suitable candidates for the further
      functional characterization of date palms.

PMID- 29596002
TI  - Imaging Bacterial Cell Wall Biosynthesis.
AB  - Peptidoglycan is an essential component of the cell wall that protects bacteria
      from environmental stress. A carefully coordinated biosynthesis of peptidoglycan
      during cell elongation and division is required for cell viability. This
      biosynthesis involves sophisticated enzyme machineries that dynamically
      synthesize, remodel, and degrade peptidoglycan. However, when and where bacteria
      build peptidoglycan, and how this is coordinated with cell growth, have been long
      standing questions in the field. The improvement of microscopy techniques has
      provided powerful approaches to study peptidoglycan biosynthesis with high
      spatiotemporal resolution. Recent development of molecular probes further
      accelerated the growth of the field, which has advanced our knowledge of
      peptidoglycan biosynthesis dynamics and mechanisms. Here, we review the
      technologies for imaging the bacterial cell wall and its biosynthesis activity.
      We focus on the applications of fluorescent d-amino acids, a newly developed type
      of probe, to visualize and study peptidoglycan synthesis and dynamics, and we
      provide direction for prospective research.

PMID- 29596003
TI  - The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol.
AB  - To maintain an asymmetric distribution of ions across membranes, protein pumps
      displace ions against their concentration gradient by using chemical energy.
      Here, we describe a functionally analogous but topologically opposite process
      that applies to the lipid transfer protein (LTP) oxysterol-binding protein
      (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide
      phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Because
      of the subsequent hydrolysis of PI(4)P, this counterexchange is irreversible and
      contributes to the establishment of a cholesterol gradient along organelles of
      the secretory pathway. The facts that some natural anti-cancer molecules block
      OSBP and that many viruses hijack the OSBP cycle for the formation of
      intracellular replication organelles highlight the importance and potency of OSBP
      mediated lipid exchange. The architecture of some LTPs is similar to that of
      OSBP, suggesting that the principles of the OSBP cycle-burning PI(4)P for the
      vectorial transfer of another lipid-might be general.

PMID- 29596004
TI  - Knowledge, Attitude, and Practice of Yoga in Medical Students: Assessment of
      Anthropometry and Lifestyle Factors.
AB  - Medical students often experience significant stress during their undergraduate
      training. Evidence has shown short-term yoga to be effective in decreasing stress
      in students. This study aimed to assess knowledge about, attitude toward, and
      practice of (KAP) yoga among medical students. A secondary objective was to
      analyze their dietary habits and physical activity. Participants consisted of 224
      medical students aged 18-23 years in pre- and paraclinical groups. A closed-ended
      KAP questionnaire was used to collect data. Anthropometric measurements were
      taken. Results showed that paraclinical students (70.5%) favorably perceived the
      health benefits of yoga. Nearly three-fourths of study subjects had previously
      practiced yoga; greater numbers intended to practice yoga in the future. About
      95.5% of the preclinical students who had done yoga had discontinued the
      practice. Perceived barriers to the practice of yoga were lack of time,
      insufficient facilities, lack of company, and lack of interest. Consideration of
      the undergraduates' lifestyle revealed that 50.4% of preclinical students did not
      exercise, and they routinely consumed more junk food with fewer servings of fresh
      fruits/salads. Preclinical students exhibited higher BMI and waist circumference
      compared to paraclinical students. Findings suggest that knowledge of and
      attitude regarding yoga were good among medical undergraduates.

PMID- 29596005
TI  - Improved Self-Acceptance, Quality of Life, and Stress Level from Participation in
      a Worksite Yoga Foundations Program: A Pilot Study.
AB  - Yoga is increasing in popularity in the United States and across the globe.
      However, most yoga programs are provided outside the worksite; although many
      companies offer worksite wellness programs, at present there is limited
      documentation regarding the potential benefits of participating in a worksite
      yoga program. Therefore, the purpose of this project was to examine the potential
      effect of a worksite yoga program on self-acceptance, quality of life, and
      perceived stress. A prospective cohort pilot study that examined a structured
      worksite yoga program was designed and tailored to individuals new to yoga. The 8
      week Yoga Foundations program was conducted at an academic medical center's
      worksite wellness center with 86 subjects. Outcome measures were the 36-item Self
      Acceptance Scale; a six-item quality-of-life measure that assesses overall,
      social, mental, physical, emotional, and spiritual well-being; and the ten-item
      Perceived Stress Scale. Participants demonstrated significant improvement in
      their overall self-acceptance ( p < 0.001), quality of life ( p < 0.001), and
      perceived stress ( p < 0.001) levels. They also highly rated the yoga instructors
      and the weekly format of the program. Participation in a Yoga Foundations program
      was associated with improvements in self-acceptance, quality of life and stress
      levels in worksite wellness center members. Future studies should use randomized
      designs and examine other wellness domains to learn more about the potential
      benefits of worksite yoga programs.

PMID- 29596006
TI  - Accuracy of Prehospital Identification of Stroke in a Large Stroke Belt
      Municipality.
AB  - OBJECTIVE: Strokes are a leading cause of morbidity and mortality in the United
      States, especially in the "stroke belt" of the southeast. Up to 65% of stroke
      patients access care by calling 9-1-1. The primary objective of this study is to
      measure the accuracy of emergency medical dispatchers (EMD) and paramedics, in
      the prehospital identification of stroke. METHODS: The study was based at Grady
      Emergency Medical Services, which is Atlanta, Georgia's public emergency medical
      services (EMS) provider. A retrospective analysis of all medically related 9-1-1
      calls to Grady EMS classified as "stroke" between January 1, 2012, and December
      31, 2012 was performed. A database was created using deterministic linkage
      between records from Grady EMS, Grady Hospital Emergency Department (ED), and the
      Grady Hospital Stroke Registry. Patients excluded were less than 18 years of age,
      had previous or concurrent head injuries, were transferred from another inpatient
      facility, and/or had incomplete patient records in any one of the three
      databases. Descriptive analysis, linear regression, and logistic multivariable
      regression were performed to discover the accuracy of stroke identification and
      contributory prehospital factors. RESULTS: A total of 548 patients were included:
      475 were transported with EMS impression of stroke and 73 with an impression
      other than stroke. The median age was 59 years, 87.4% were black, and 52.6% were
      female. Paramedics adhered to all seven elements of the Grady EMS stroke protocol
      in 76.4% (n = 363) of suspected stroke cases. Sensitivity and positive predictive
      value for paramedic stroke identification was 76.2% and 49.3%, respectively, and
      for EMD, was 48.9% and 24%, respectively. Identification of hemorrhagic strokes
      had a relatively lower sensitivity. Paramedics were more likely to positively
      identify strokes when the Cincinnati Prehospital Stroke Scale (CPSS) screen was
      positive, or when classified by EMD as stroke. Paramedics were less likely to
      identify stroke in female patients. Paramedics' diagnostic accuracy was similar
      regardless of their adherence to the EMS stroke care protocol. CONCLUSIONS: EMD
      and EMS personnel in a large city in the Southeastern United States, with high
      stroke prevalence, had a relatively high sensitivity in identifying acute stroke
      patients. Paramedic accuracy was augmented by positive CPSS screening and by EMD
      recognition of stroke.

PMID- 29596007
TI  - Outpatient physical therapy cardiovascular assessment: Physical therapist
      perspective and experience.
AB  - BACKGROUND: Physical therapists are recognized healthcare providers who play an
      important role in cardiovascular disease prevention. Heart rate (HR) and blood
      pressure (BP) are important parameters in cardiovascular risk assessment;
      however, physical therapists do not usually integrate them into clinical
      practice. Therefore, this study aimed to examine the current practice and opinion
      of outpatient physical therapists toward HR and BP measurements in clinics.
      METHODS: A 12-item survey questionnaire was distributed to outpatient physical
      therapists. Five senior staff from different specialties, including orthopedic,
      neurology, pediatric, cardiopulmonary, and sport specialties, participated in a
      focus group interview to gather their opinions. RESULTS: In total, 285 (56%:
      male) physical therapists participated. Only 68 (24%) measured HR and BP; of
      these, 27 (41%) used manual sphygmomanometers. Nearly one-fifth reported that
      cardiovascular adverse events, such as syncope and chest pain, occurred during
      therapeutic exercise of their patients and were the highest among the sport and
      orthopedic physical therapists. Most physical therapists felt that measuring
      cardiovascular indices is not their job and does not add value to their treatment
      plan. CONCLUSION: Majority of the physical therapists were not measuring HR and
      BP during clinical assessment, although some reported cardiovascular adverse
      events occurring in their patients.

PMID- 29596008
TI  - Psychotropic medications for highly vulnerable children.
AB  - INTRODUCTION: At least 20% of children in the U.S. are highly vulnerable because
      they lack healthcare and protection. Several factors produce vulnerability:
      trauma, disruptions of parenting, poverty, involvement in the juvenile justice
      and/or child welfare systems, residence in restrictive settings, and problems
      related to developmental disabilities. These children receive psychotropic
      medications at high rates, raising numerous concerns. Areas covered: The authors
      begin this review with a description of the population of highly vulnerable
      children. They then follow this with a review of the effectiveness and side
      effects of psychotropic medications for their most common diagnoses, using the
      highest-quality systematic reviews identified by multiple database searches.
      Expert opinion: Highly vulnerable children receive numerous psychotropic
      medications with high rates of polypharmacy, off-label use, and long-term use,
      typically in the absence of adjunctive psychosocial interventions. The current
      evidence contravenes these trends. Future studies of psychotropic medications in
      vulnerable children should include long-term effectiveness trials and
      polypharmacy in conjunction with evidence-based, family-centered, psychosocial
      treatments.

PMID- 29596009
TI  - Decreased Time from 9-1-1 Call to PCI among Patients Experiencing STEMI Results
      in a Decreased One Year Mortality.
AB  - BACKGROUND: The impact on mortality due to prompt recognition of ST-segment
      Elevation Myocardial Infarction (STEMI) patients by EMS has not been well
      described. The objective of this study was to describe the association between
      the time interval, 9-1-1 call to percutaneous intervention (PCI), and mortality
      at one year. METHODS: This retrospective analysis included patients that were
      transported by EMS as a "code STEMI" and underwent PCI.  Total time from 9-1-1
      call to PCI was calculated for each patient and was the independent variable of
      interest. Each patient's mortality status at one year was the outcome variable,
      collected by querying medical records and the national death index. Confounding
      variables were abstracted from hospital records. Logistic regression was
      conducted to determine the likelihood of survival given differences in time to
      PCI. RESULTS: A total of 550 patients were included in the analyses of which 68%
      were male with an average age 59.8 (SD 12.8). Mean reperfusion time was 81.8 min
      (SD 20.0) and was significantly lower in patients alive at one year (80.8 min, SD
      19.7) vs. deceased at one year (93.9 min, SD 19.6), respectively. Odds of
      survival at one year decreased by 3% (OR 0.97; 95% CI 0.96-0.99) for every one
      minute increase in time to PCI. This relationship practically represents a 30%
      increase in mortality for every 10 minute delay from 9-1-1 call to PCI.
      CONCLUSION: The model produced suggests that a linear relationship exists between
      time to PCI and mortality in the prehospital environment with the probability of
      survival decreasing significantly as time to PCI increases.

PMID- 29596010
TI  - Whole body vibration on people with sequelae of polio.
AB  - PURPOSE: The purpose was to explore the feasibility of whole body vibration (WBV)
      on polio survivors with/without post-polio syndrome (PPS) by studying its effects
      on walking speed (10-m walk test), endurance (2-min walk test), pain
      severity/interference (Brief Pain Inventory [BPI]), sleep quality (Pittsburg
      Sleep Quality Index), fatigue (Fatigue Severity Scale), leg strength (manual
      muscle testing and hand-held dynamometry), and muscle cramping (written logs).
      METHODS: Fifteen individuals completed the study, participating in eight sessions
      in two 4-week blocks. Participants started with ten 1-min vibration
      bouts/session, increasing to 20 min. Low (amplitude 4.53 mm, g force 2.21) and
      higher (amplitude 8.82 mm, g force 2.76) intensity blocked intervention occurred
      in random order crossover design. Blinded testing ensued before/after
      intervention blocks and at follow-up. RESULTS: No study-related adverse events
      occurred. Participants starting first with higher intensity intervention improved
      in walking speed (p = 0.017). BPI pain severity significantly improved (p =
      0.049) after higher intensity intervention. No significant changes were found
      after low intensity vibration or in other outcome measures. CONCLUSIONS: WBV
      appears to be a safe exercise for this population. Long-term use in polio
      survivors needs to be researched, particularly in reducing barriers to
      participation to promote the physical aspects of health.

PMID- 29596011
TI  - Slow Infusion of Recombinant Adeno-Associated Viruses into the Mouse
      Cerebrospinal Fluid Space.
AB  - Recombinant adeno-associated viruses (rAAVs) are the leading in vivo gene
      delivery platform, and have been extensively studied in gene therapy targeting
      various tissues, including the central nervous system (CNS). A single-bolus rAAV
      injection to the cerebrospinal fluid (CSF) space has been widely used to target
      the CNS, but it suffers from several drawbacks, such as leakage to peripheral
      tissues. Here, a protocol is described using an osmotic pump to infuse rAAV
      slowly into the mouse CSF space. Compared to the single-bolus injection
      technique, pump infusion can lead to higher CNS transduction and lower
      transduction in the peripheral tissues.

PMID- 29596012
TI  - Utility of natriuretic peptides to assess and manage patients with heart failure
      receiving angiotensin receptor blocker/neprilysin inhibitor therapy.
AB  - Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal
      fragment of its prohormone (NT-proBNP), are well-established biomarkers for
      patients with heart failure (HF). Although these biomarkers have consistently
      demonstrated their value in the diagnosis and prognostication of HF, their
      ability to help clinicians in making treatment decisions remains debated.
      Moreover, some new HF drugs can affect concentrations of NPs, such as the
      prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors
      (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use
      of NT-proBNP measurement has been suggested in the context of ARNI therapy
      because its concentrations are not affected by neprilysin inhibition. As
      biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the
      effects of individual patient characteristics, such as renal function and age, on
      biomarker concentrations should be reassessed.

PMID- 29596013
TI  - The 2016 Earthquake in Ecuador: Zika Outbreak After a Natural Disaster.
AB  - The objective of this work was to examine the spread of the Zika virus after the
      destructive impact of the earthquake of April 2016 along the coast of Ecuador.
      Using a difference-in-difference estimation method and a unique dataset to track
      Zika cases at the national level, we estimated the impact of the earthquake on
      the reported cases of Zika in the affected region. Our results suggest that the
      earthquake increased the reported cases of Zika by 0.509 per epidemiologic week
      (data per 10,000 population), and we argue that the destroyed built environment
      along with other factors created a disease focus, where the virus spread easily.
      Because of its potential complications and devastating long-term effects, Zika
      represents a national threat. After a natural disaster, the health authorities,
      together with a multidisciplinary team and the wider community, all have an
      urgent responsibility to collaborate to minimize the health risks to the
      population.

PMID- 29596014
TI  - Lower tendon stiffness in very old compared with old individuals is unaffected by
      short-term resistance training of skeletal muscle.
AB  - Aging negatively affects collagen-rich tissue, like tendons, but in vivo tendon
      mechanical properties and the influence of physical activity after the 8th decade
      of life remain to be determined. This study aimed to compare in vivo patellar
      tendon mechanical properties in moderately old (old) and very old adults and the
      effect of short-term resistance training. Twenty old (9 women, 11 men, >65 yr)
      and 30 very old (11 women, 19 men, >83 yr) adults were randomly allocated to
      heavy resistance training (HRT) or no training (CON) and underwent testing of in
      vivo patellar tendon (PT) mechanical properties and PT dimensions before and
      after a 3-mo intervention. Previous measurements of muscle properties, blood
      parameters, and physical activity level were included in the analysis. Data from
      9 old HRT, 10 old CON, 14 very old CON, and 12 old HRT adults were analyzed. In
      addition to lower quadriceps muscle strength and cross-sectional area (CSA), we
      found lower PT stiffness and Young's modulus ( P < 0.001) and a trend toward the
      lower mid-portion PT-CSA ( P = 0.09) in very old compared with old subjects.
      Daily step count was also lower in very old subjects ( P < 0.001). Resistance
      training improved muscle strength and cross-sectional area equally in old and
      very old subjects ( P < 0.05) but did not affect PT mechanical properties or
      dimension. We conclude that PT material properties are reduced in very old age,
      and this may likely be explained by reduced physical activity. Three months of
      resistance training however, could not alter PT mechanical properties in very old
      individuals. NEW & NOTEWORTHY This research is the first to quantify in vivo
      tendon mechanical properties in a group of very old adults in their eighties.
      Patellar tendon stiffness was lower in very old (87 yr on average) compared with
      moderately old (68 yr on average) individuals. Reduced physical activity with
      aging may explain some of the loss in tendon stiffness, but regular heavy
      resistance training for 3 mo was not sufficient to change tendon mechanical
      properties.

PMID- 29596015
TI  - Continuous negative abdominal pressure: mechanism of action and comparison with
      prone position.
AB  - We recently reported that continuous negative abdominal pressure (CNAP) could
      recruit dorsal atelectasis in experimental lung injury and that oxygenation
      improved at different transpulmonary pressure values compared with increases in
      airway pressure (Yoshida T, Engelberts D, Otulakowski G, Katira BH, Post M,
      Ferguson ND, Brochard L, Amato MBP, Kavanagh BP. Am J Respir Crit Care Med 197:
      534-537, 2018). The mechanism of recruitment with CNAP is uncertain, and its
      impact compared with a commonly proposed alternative approach to recruitment,
      prone positioning, is not known. We hypothesized that CNAP recruits lung by
      decreasing the vertical pleural pressure (Ppl) gradient (i.e., difference between
      dependent and nondependent Ppl), thought to be one mechanism of action of prone
      positioning. An established porcine model of lung injury (surfactant depletion
      followed by ventilator-induced lung injury) was used. CNAP was applied using a
      plexiglass chamber that completely enclosed the abdomen at a constant negative
      pressure (-5 cmH2O). Lungs were recruited to maximal positive end-expiratory
      pressure (PEEP; 25 cmH2O) and deflated in steps of PEEP (2 cmH2O, 10 min each).
      CNAP lowered the Ppl in dependent but not in nondependent lung, and therefore, in
      contrast to PEEP, it narrowed the vertical Ppl gradient. CNAP increased
      respiratory system compliance and oxygenation and appeared to selectively
      displace the posterior diaphragm caudad (computerized tomography images).
      Compared with prone position without CNAP, CNAP in the supine position was
      associated with higher arterial partial pressure of oxygen and compliance, as
      well as greater homogeneity of ventilation. The mechanism of action of CNAP
      appears to be via selective narrowing of the vertical gradient of Ppl. CNAP
      appears to offer physiological advantages over prone positioning. NEW &
      NOTEWORTHY Continuous negative abdominal pressure reduces the vertical gradient
      in (dependent vs. nondependent) pleural pressure and increases oxygenation and
      lung compliance; it is more effective than prone positioning at comparable levels
      of positive end-expiratory pressure.

PMID- 29596017
TI  - Mechanisms for the increased fatigability of the lower limb in people with type 2
      diabetes.
AB  - Fatiguing exercise is the basis of exercise training and a cornerstone of
      management of type 2 diabetes mellitus (T2D); however, little is known about the
      fatigability of limb muscles and the involved mechanisms in people with T2D. The
      purpose of this study was to compare fatigability of knee extensor muscles
      between people with T2D and controls without diabetes and determine the neural
      and muscular mechanisms for a dynamic fatiguing task. Seventeen people with T2D
      [ten men and seven women: 59.6 (9.0) yr] and twenty-one age-, body mass index-,
      and physical activity-matched controls [eleven men and ten women: 59.5 (9.6) yr]
      performed one hundred twenty high-velocity concentric contractions (one
      contraction/3 s) with a load equivalent to 20% maximal voluntary isometric
      contraction (MVIC) torque with the knee extensors. Transcranial magnetic
      stimulation (TMS) and electrical stimulation of the quadriceps were used to
      assess voluntary activation and contractile properties. People with T2D had
      larger reductions than controls in power during the fatiguing task [42.8 (24.2)
      vs. 26.4 (15.0)%; P < 0.001] and MVIC torque after the fatiguing task [37.6
      (18.2) vs. 26.4 (12.1)%; P = 0.04]. People with T2D had greater reductions than
      controls in the electrically evoked twitch amplitude after the fatiguing task
      [44.0 (20.4) vs. 35.4 (12.1)%, respectively; P = 0.01]. However, the decrease in
      voluntary activation was similar between groups when assessed with electrical
      stimulation [12.1 (2.6) vs. 12.4 (4.4)% decrease; P = 0.84] and TMS ( P = 0.995).
      A greater decline in MVIC torque was associated with larger reductions of twitch
      amplitude ( r2 = 0.364, P = 0.002). Although neural mechanisms contributed to
      fatigability, contractile mechanisms were responsible for the greater knee
      extensor fatigability in men and women with T2D compared with healthy controls.
      NEW & NOTEWORTHY Transcranial magnetic stimulation and percutaneous muscle
      stimulation were used to determine the contributions of neural and contractile
      mechanisms of fatigability of the knee extensor muscles after a dynamic fatiguing
      task in men and women with type 2 diabetes (T2D) and healthy age-, body mass
      index-, and physical activity-matched controls. Although neural and contractile
      mechanisms contributed to greater fatigability of people with T2D, fatigability
      was primarily associated with impaired contractile mechanisms and glycemic
      control.

PMID- 29596016
TI  - Chronic interval exercise training prevents BKCa channel-mediated coronary
      vascular dysfunction in aortic-banded miniswine.
AB  - Conventional treatments have failed to improve the prognosis of heart failure
      with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this
      study was to determine the therapeutic efficacy of chronic interval exercise
      training (IT) on large-conductance Ca2+-activated K+ (BKCa) channel-mediated
      coronary vascular function in heart failure. We hypothesized that chronic
      interval exercise training would attenuate pressure overload-induced impairments
      to coronary BKCa channel-mediated function. A translational large-animal model
      with cardiac features of HFpEF was used to test this hypothesis. Specifically,
      male Yucatan miniswine were divided into three groups ( n = 7/group): control
      (CON), aortic banded (AB)-heart failure (HF), and AB-interval trained (HF-IT).
      Coronary blood flow, vascular conductance, and vasodilatory capacity were
      measured after administration of the BKCa channel agonist NS-1619 both in vivo
      and in vitro in the left anterior descending coronary artery and isolated
      coronary arterioles, respectively. Skeletal muscle citrate synthase activity was
      decreased and left ventricular brain natriuretic peptide levels increased in HF
      vs. CON and HF-IT animals. A parallel decrease in NS-1619-dependent coronary
      vasodilatory reserve in vivo and isolated coronary arteriole vasodilatory
      responsiveness in vitro were observed in HF animals compared with CON, which was
      prevented in the HF-IT group. Although exercise training prevented BKCa channel
      mediated coronary vascular dysfunction, it did not change BKCa channel alpha
      subunit mRNA, protein, or cellular location (i.e., membrane vs. cytoplasm). In
      conclusion, these results demonstrate the viability of chronic interval exercise
      training as a therapy for central and peripheral adaptations of experimental
      heart failure, including BKCa channel-mediated coronary vascular dysfunction. NEW
      & NOTEWORTHY Conventional treatments have failed to improve the prognosis of
      heart failure with preserved ejection fraction (HFpEF) patients. Our findings
      show that chronic interval exercise training can prevent BKCa channel-mediated
      coronary vascular dysfunction in a translational swine model of chronic pressure
      overload-induced heart failure with relevance to human HFpEF.

PMID- 29596018
TI  - The STAR Data Reporting Guidelines for Clinical High Altitude Research.
AB  - : Brodmann Maeder, Monika, Hermann Brugger, Matiram Pun, Giacomo Strapazzon,
      Tomas Dal Cappello, Marco Maggiorini, Peter Hackett, Peter Baartsch, Erik R.
      Swenson, Ken Zafren (STAR Core Group), and the STAR Delphi Expert Group. The
      STARdata reporting guidelines for clinical high altitude research. High
      AltMedBiol. 19:7-14, 2018. AIMS: The goal of the STAR (STrengthening Altitude
      Research) initiative was to produce a uniform set of key elements for research
      and reporting in clinical high-altitude (HA) medicine. The STAR initiative was
      inspired by research on treatment of cardiac arrest, in which the establishment
      of the Utstein Style, a uniform data reporting protocol, substantially
      contributed to improving data reporting and subsequently the quality of
      scientific evidence. MATERIALS AND METHODS: The STAR core group used the Delphi
      method, in which a group of experts reaches a consensus over multiple rounds
      using a formal method. We selected experts in the field of clinical HA medicine
      based on their scientific credentials and identified an initial set of parameters
      for evaluation by the experts. RESULTS: Of 51 experts in HA research who were
      identified initially, 21 experts completed both rounds. The experts identified 42
      key parameters in 5 categories (setting, individual factors, acute mountain
      sickness and HA cerebral edema, HA pulmonary edema, and treatment) that were
      considered essential for research and reporting in clinical HA research. An
      additional 47 supplemental parameters were identified that should be reported
      depending on the nature of the research. CONCLUSIONS: The STAR initiative, using
      the Delphi method, identified a set of key parameters essential for research and
      reporting in clinical HA medicine.

PMID- 29596020
TI  - Regional Deposition of Particles Within the Respiratory Tract Should Be Linked to
      Impaction Parameter, Not Aerodynamic Size.

PMID- 29596019
TI  - Abstracts from The Aerosol Society Drug Delivery to the Lungs 28 Edinburgh
      International Conference Centre Edinburgh, Scotland, UK December 6-8, 2017.

PMID- 29596022
TI  - 3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon
      derived stem cells through a PI3K/AKT signaling pathway.
AB  - The tendon is a mechanosensitive tissue, but little is known about how mechanical
      stimulation selectively signals tenogenic differentiation and neo-tendon
      formation. In this study, we compared the impact of uniaxial and biaxial
      mechanical loading on tendon-derived stem cells (TDSCs). Our data show that there
      are variations in cell signaling and cell differentiation of mouse TDSCs in
      response to uniaxial and biaxial loading in monolayer culture. Whereas uniaxial
      loading induced TDSCs toward tenogenic and osteogenic differentiation, biaxial
      loading induced osteogenic, adipogenic, and chondrogenic differentiation of
      TDSCs. Furthermore, by applying uniaxial loading on 3-dimensional (3D) TDSC
      constructs, tenogenic-specific differentiation and neo-tendon formation were
      observed, results that were replicated in human TDSCs. We also showed that
      uniaxial loading induced PKB (AKT) phosphorylation (pAKT), whereas biaxial
      loading induced pERK. Most importantly, we found that inhibition of the PI3K/AKT
      signaling pathway could attenuate tenogenic differentiation and tendon formation
      in 3D TDSC constructs subjected to uniaxial loading. Taken together, our study
      highlights the importance of appropriate mechanobiological stimulation in 3D cell
      niches on tendon-like tissue formation and demonstrates that uniaxial mechanical
      loading plays an essential role in tenogenic differentiation and tendon formation
      by activating the PI3K/AKT signaling pathway.-Wang, T., Thien, C., Wang, C., Ni,
      M., Gao, J., Wang, A., Jiang, Q., Tuan, R. S., Zheng, Q., Zheng, M. H. 3D
      uniaxial mechanical stimulation induces tenogenic differentiation of tendon
      derived stem cells through a PI3K/AKT signaling pathway.

PMID- 29596024
TI  - Autocrine actions of prolactin contribute to the regulation of lactotroph
      function in vivo.
AB  - Prolactin (PRL), whose principal role is regulation of lactation, is mainly
      synthesized and secreted by lactotroph anterior pituitary cells. Its signaling is
      exerted via a transmembrane PRL receptor (PRLR) expressed in a wide variety of
      tissues, including the anterior pituitary. Dopamine, which is secreted by
      tuberoinfundibular hypothalamic neurons, is the major inhibitory regulator of
      prolactin secretion. Although PRL is well established to stimulate hypothalamic
      dopamine secretion, thereby exerting a negative feedback regulation on its own
      release, autocrine or paracrine actions of PRL on lactotroph cells have also been
      suggested. Within the pituitary, PRL may inhibit both lactotroph proliferation
      and secretion, but in vivo evaluation of these putative functions is limited. To
      determine whether the autocrine actions of prolactin have a significant role in
      the physiologic function of lactotrophs in vivo, we examined the consequences of
      conditional deletion of Prlr in lactotroph cells using a novel mouse line with
      loxP sites flanking the Prlr gene ( Prlrlox/lox) and Cre-recombinase (Cre)
      expressed under the control of the pituitary-specific Prl promoter.
      Prlrlox/lox/Prl-Cre mice have normal PRL levels and did not develop any pituitary
      lactotroph adenoma, even at 20 mo of age. Nevertheless, Prlrlox/lox/Prl-Cre mice
      displayed an increased dopaminergic inhibitory tone compared with control
      Prlrlox/lox mice. These results elegantly confirm an autocrine/paracrine feedback
      of PRL on lactotroph cells in vivo, which can be fully compensated by an intact
      hypothalamic feedback system.-Bernard, V., Lamothe, S., Beau, I., Guillou, A.,
      Martin, A., Le Tissier, P., Grattan, D., Young, J., Binart, N. Autocrine actions
      of prolactin contribute to the regulation of lactotroph function in vivo.

PMID- 29596023
TI  - Inflammation-induced lymphatic architecture and bone turnover changes are
      ameliorated by irisin treatment in chronic inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic disease with gastrointestinal
      dysfunction as well as comorbidities such as inflammation-induced bone loss and
      impaired immune response. Current treatments for IBD all have negative,
      potentially severe side effects. We aimed to test whether exogenous treatment
      with irisin, a novel immunomodulatory adipomyokine, could ameliorate IBD-induced
      lymphatic and bone alterations. Irisin treatment improved both gut and bone
      outcomes by mitigating inflammation and restoring structure. In the gut, IBD
      caused colonic lymphatic hyperproliferation into the mucosal and submucosal
      compartments. This proliferation in the rodent model is akin to what is observed
      in IBD patient case studies. In bone, IBD increased osteoclast surface and
      decreased bone formation. Both gut and osteocytes in bone exhibited elevated
      levels of TNF-alpha and receptor activator of NF-kappaB ligand (RANKL) protein
      expression. Exogenous irisin treatment restored normal colonic lymphatic
      architecture and increased bone formation rate concurrent with decreased
      osteoclast surfaces. After irisin treatment, gut and osteocyte TNF-alpha and
      RANKL protein expression levels were no different from vehicle controls. Our data
      indicate that the systemic immunologic changes that occur in IBD are initiated by
      damage in the gut and likely linked through the lymphatic system. Additionally,
      irisin is a potential novel intervention mitigating both local inflammatory
      changes in the gut and distant changes in bone.-Narayanan, S. A., Metzger, C. E.,
      Bloomfield, S. A., Zawieja, D. C. Inflammation-induced lymphatic architecture and
      bone turnover changes are ameliorated by irisin treatment in chronic inflammatory
      bowel disease.

PMID- 29596025
TI  - Palliative Care Consultation in Advanced Chronic Kidney Disease with Pain.
AB  - BACKGROUND: There is little data on pain management in patients with advanced
      chronic kidney disease (CKD) who have opted for palliative care. OBJECTIVE: We
      investigated the prevalence, severity and management of pain in advanced CKD
      patients attending Renal Palliative Care out-patient clinics under our Division.
      METHODS: Consecutive patients referred to the Renal Palliative Care Clinics at
      two hospitals under our Division from July 2012 to June 2016 were included. All
      the patients were managed according to a multi-disciplinary protocol led by
      palliative care specialists, including serial assessments with the Edmonton
      Symptom Assessment System. MEASUREMENTS: Response to pain management was defined
      as a difference by 2 points or more, and factors predictive of response were
      assessed by logistic regression. RESULTS: Data from 253 patients were analyzed.
      Of them 107 patients (42%) experienced pain symptoms: 45 patients (42.1%) rated
      their pain as mild (score 0-3), 51 (47.7%) as moderate (NRS score 4-6), and 11
      (10.2%) as severe (score 7-10) by using numerical rating scale. The response rate
      to pain management was 53.2%. Neuropathic pain was a predictor for lack of
      response. DISCUSSION: Pain is common in advanced CKD patients receiving
      palliative care. While this seems to have been underrecognized, the symptom is
      potentially amenable to management. We recommend routine assessment of pain
      burden in this patient population.

PMID- 29596027
TI  - Optimization aspects of the biological nitrogen removal process in a full-scale
      twin sequencing batch reactor (SBR) system in series treating landfill leachate.
AB  - Despite the fact that biological nitrogen removal (BNR) process has been studied
      in detail in laboratory- and pilot-scale sequencing batch reactor (SBR) systems
      treating landfill leachate, a limited number of research works have been
      performed in full-scale SBR plants regarding nitrification and denitrification.
      In the current study, a full-scale twin SBR system in series of 700 m3 (350 m3
      each) treating medium-age landfill leachate was evaluated in terms of its carbon
      and nitrogen removal efficiency in the absence and presence of external carbon
      source, i.e., glycerol from biodiesel production. Both biodegradable organic
      carbon and ammonia were highly oxidized [biochemical oxygen demand (BOD5) and
      total Kjehldahl nitrogen (TKN) removal efficiencies above 90%], whereas chemical
      oxygen demand (COD) removal efficiency was slightly above 40%, which is within
      the range reported in the literature for pilot-scale SBRs. As the consequence of
      the high recalcitrant organic fraction of the landfill leachate, dissimilatory
      nitrate reduction was restricted in the absence of crude glycerol, although
      denitrification was improved by electron donor addition, resulting in TN removal
      efficiencies above 70%. Experimental data revealed that the second SBR negligibly
      contributed to BNR process, since carbon and ammonia oxidation completion was
      achieved in the first SBR. On the other hand, the low VSS/SS ratio, due to the
      lack of primary sedimentation, highly improved sludge settleability, resulting in
      sludge volume indices (SVI) below 30 mL g-1.

PMID- 29596026
TI  - Environmental factors influencing landfill gas biofiltration: Lab scale study on
      methanotrophic bacteria growth.
AB  - The post-management of landfills represents an important challenge for landfill
      gas treatment. Traditional systems (energy recovery, flares, etc.) present
      technical problems in treating flow with low methane (CH4) concentrations. The
      objective of this study was to isolate methanotrophic bacteria from a field-scale
      biofilter in order to study the bacteria in laboratories and evaluate the
      environmental factors that mostly influence Microbial Aerobic Methane Oxidation
      (MAMO). The soil considered was sampled from the biofilter located in the
      landfill of Venosa (Basilicata Region, Italy) and it was mainly composed of wood
      chips and compost. The results showed that methanotrophic microorganisms are
      mainly characterized by a slow growth and a significant sensitivity to CH4
      levels. Temperature and nitrogen (N) also have a very important role on their
      development. On the basis of the results, biofilters for biological CH4 oxidation
      can be considered a viable alternative to mitigate CH4 emissions from landfills.

PMID- 29596028
TI  - Expression and functional analysis of three nicosulfuron-degrading enzymes from
      Bacillus subtilis YB1.
AB  - To investigate the degradation activity of the manganese ABC transporter,
      vegetative catalase 1 and acetoin dehydrogenase E1 from Bacillus subtilis YB1,
      the proteins were prokaryotically expressed and purified. Assay results showed
      that the three enzymes were able to degrade nicosulfuron (2- (4,6
      dimethoxypyrimidine-2-pyrimidinylcarbamoylaminosulfonyl) -N,N
      dimethylnicotinamide), with vegetative catalase 1 exhibiting the highest
      activity. To further examine the degradation pathway, the degradation products of
      the three enzymes and the YB1 strain were detected by liquid chromatography-mass
      spectrometry(LC-MS). The nicosulfuron degradation products of the three enzymes
      were consistent with those of the YB1 strain, indicating the presence of two
      pathways: one due to cleavage of sulfonylurea bridges and ring-opening of 1-(4,6
      dimethoxy-pyrimidin-2-yl)-3-(2-methyliminomethanesulfonyl-acetyl)-ureaas the
      pyrimidine ring, yielding the product; and the another due to cleavage of a
      sulfonylurea bridge, yielding 4,6-dihydroxy pyrimidine (111 m/z), 2-ylamine -4,6
      dimethoxy pyrimidine and ((4-(dimethycarbamoyl)pyridine-2-yl)sulfonyl)carbamic
      acid as products, which were further degraded to 4,6-dihydroxy pyrimidine and N,N
      dimethyl-2-sulfamoyl-isonicotinamide. The above results reveal a major
      contribution of extracellular enzymes to the degradation of nicosulfuron by the
      YB1 strain. Our data help in elucidation of the mechanism of nicosulfuron bio
      degradation and may facilitate the construction of engineered strains.

PMID- 29596029
TI  - Phase II Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced
      Non-Small-Cell Lung Cancer.
AB  - Purpose Approximately 1% to 2% of non-small-cell lung cancers (NSCLCs) harbor a c
      ros oncogene 1 ( ROS1) rearrangement. Crizotinib, an inhibitor of anaplastic
      lymphoma kinase (ALK), ROS1, and MET, has shown marked antitumor activity in a
      small expansion cohort of patients with ROS1-positive advanced NSCLC from an
      ongoing phase I study. We assessed the efficacy and safety of crizotinib in the
      largest cohort of patients with ROS1-positive advanced NSCLC. Patients and
      Methods This phase II, open-label, single-arm trial enrolled East Asian patients
      with ROS1-positive (assessed through validated AmoyDx assay [Amoy Diagnostics,
      Xiamen, China] at three regional laboratories) advanced NSCLC who had received
      three or fewer lines of prior systemic therapies. Patients were to receive oral
      crizotinib at a starting dose of 250 mg twice daily and continued treatment until
      Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1-defined
      progression (by independent radiology review [IRR]), unacceptable toxicity, or
      withdrawal of consent. The primary end point was objective response rate (ORR) by
      IRR. Results In the efficacy and safety analyses, 127 patients were included,
      with 49.6% still receiving treatment at data cutoff. ORR by IRR was 71.7% (95%
      CI, 63.0% to 79.3%), with 17 complete responses and 74 partial responses. ORRs
      were similar irrespective of the number of prior lines of therapy, and responses
      were durable (median duration of response, 19.7 months; 95% CI, 14.1 months to
      not reached). Median progression-free survival by IRR was 15.9 months (95% CI,
      12.9 to 24.0 months). No new safety signals associated with crizotinib were
      reported. Conclusion This study demonstrated clinically meaningful benefit and
      durable responses with crizotinib in East Asian patients with ROS1-positive
      advanced NSCLC. Crizotinib was generally well tolerated, with a safety profile
      consistent with previous reports.

PMID- 29596031
TI  - Incorporating Genuine Prior Information about Between-Study Heterogeneity in
      Random Effects Pairwise and Network Meta-analyses.
AB  - BACKGROUND: Pairwise and network meta-analyses using fixed effect and random
      effects models are commonly applied to synthesize evidence from randomized
      controlled trials. The models differ in their assumptions and the interpretation
      of the results. The model choice depends on the objective of the analysis and
      knowledge of the included studies. Fixed effect models are often used because
      there are too few studies with which to estimate the between-study SD from the
      data alone. OBJECTIVES: The aim of this study was to propose a framework for
      eliciting an informative prior distribution for the between-study SD in a
      Bayesian random effects meta-analysis model to genuinely represent heterogeneity
      when data are sparse. METHODS: We developed an elicitation method using external
      information, such as empirical evidence and expert beliefs, on the "range" of
      treatment effects to infer the prior distribution for the between-study SD. We
      also developed the method to be implemented in R. RESULTS: The 3-stage
      elicitation approach allows uncertainty to be represented by a genuine prior
      distribution to avoid making misleading inferences. It is flexible to what
      judgments an expert can provide and is applicable to all types of outcome
      measures for which a treatment effect can be constructed on an additive scale.
      CONCLUSIONS: The choice between using a fixed effect or random effects meta
      analysis model depends on the inferences required and not on the number of
      available studies. Our elicitation framework captures external evidence about
      heterogeneity and overcomes the assumption that studies are estimating the same
      treatment effect, thereby improving the quality of inferences in decision making.

PMID- 29596030
TI  - Potential Value of YAP Staining in Rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a common malignancy of soft tissue, subclassified as
      alveolar (ARMS), pleomorphic (PRMS), spindle cell/sclerosing (SRMS), and
      embryonal (ERMS) types. The Yes-associated protein (YAP) is a member of the Hippo
      pathway and a transcriptional regulator that controls cell proliferation. We have
      studied the immunohistochemical expression of YAP in different RMSs, arranged in
      tissue microarray (TMA) and whole slide formats. Pertinent clinical data
      including patient age, gender, tumor location, and clinical stage were collected.
      Out of 96 TMA cases, 30 cases (31%) were pleomorphic, 27 (28%) were embryonal, 24
      (25%) alveolar, and 15 (16%) spindle cell. Positive nuclear YAP staining was seen
      in the PRMS (17/30, 56.7%), SRMS (7/15, 46.7%), ERMS (19/27 or 70%), and less in
      ARMS (37.5%). YAP nuclear staining was significantly more prevalent in ERMS than
      ARMS ( p=0.02). Of the 41 whole slide cases, nuclear staining was detected in all
      ARMS but was restricted in distribution to <30% of the cells, in contrast to ERMS
      and SRMS, which had diffuse or >30% staining. These results highlight the role of
      YAP in RMS tumorigenesis, a fact that can be useful in engineering targeted
      therapy. Restricted nuclear YAP staining (<30% of cells) may be of value in the
      diagnosis of ARMS.

PMID- 29596033
TI  - High Prevalence of Ocular Surface Disease Among Glaucoma Patients in Thailand.
AB  - PURPOSE: To determine the prevalence of symptoms and signs of ocular surface
      disease (OSD) among Thai patients with glaucoma receiving topical intraocular
      pressure (IOP)-lowering therapy. METHODS: Consecutive patients with glaucoma were
      recruited prospectively for this cross-sectional study from Siriraj Hospital.
      Subjective symptoms were evaluated using the Ocular Surface Disease Index (OSDI),
      and objective clinical signs were evaluated using the tear breakup time (TBUT),
      corneal fluorescein, rose bengal staining, and the Schirmer test. RESULTS: One
      hundred nine patients (56% women; mean age, 64.0 +/- 13.7 years) were included.
      The mean number of IOP-lowering eye drops instilled daily was 3.2 +/- 2.4; the
      mean duration of treatment was 5.4 +/- 3.9 years. Forty-two (38.5%) patients
      reported symptoms using the OSDI. The TBUT was normal in 1 patient, and the
      others (99.1%) had abnormal tear quality. Fluorescein and rose bengal staining
      showed positive results in 35 (32.1%) and 42 (38.6%) patients, respectively. The
      Schirmer test showed decreased tear production in 80 (73.4%) patients. A greater
      number of IOP-lowering eye drops daily was associated significantly with 3.8 and
      4.4 times higher odds of abnormal corneal fluorescein and rose bengal staining,
      respectively (95% confidence interval [CI], 1.62-9.34, P = 0.002 and 95% CI, 1.91
      10.32, P = 0.001, respectively). A significant (P = 0.03, 0.04) correlation was
      seen between OSDI and corneal dye staining tests. CONCLUSIONS: A high prevalence
      of OSD was found among glaucoma patients in Thailand. OSD is more prevalent in
      Asians than in westerners. Awareness regarding prescribing multiple IOP-lowering
      eye drops in Asians should be heightened to avoid ocular surface toxicity.

PMID- 29596032
TI  - Occurrence and Characterization of Carbapenemase-Producing Enterobacteriaceae in
      a Tunisian Hospital.
AB  - Carbapenem-resistant Enterobacteriaceae have become of particular concern, since
      they were quickly disseminated in various areas in the world. The aim of the
      study was to investigate the prevalence of carbapenemase production among
      clinical isolates of Enterobacteriaceae recovered from the Military Hospital of
      Tunisia. Bacterial isolates (n = 125) were recovered from patients in diverse
      services from March 2014 to February 2016 and identified by Vitek II Compact(r).
      The multiplex PCR for blaVIM, blaIMP, blaNDM, blaKPC, and blaOXA-48 with
      subsequent amplicon detection by reverse hybridization was performed with the
      Hyplex SuperBug ID test system (AmplexDiagnostics GmbH, Gars-Bahnhof, Germany).
      The 125 strains showed resistance to carbapenems of which 102 strains (81.6%)
      were carbapenemase-producing Enterobacteriaceae and were identified as Klebsiella
      pneumoniae (85.2%), Enterobacter cloacae (9.8%), Escherichia coli (2.9%),
      Providencia stuartii (0.9%) and Enterobacter aerogenes (0.9%). These strains were
      isolated mainly from blood, anal, and urine samples. Patients were mainly
      hospitalized in the intensive care units, surgery, and medical services. All
      strains were resistant to ertapenem (100%) and 55.8% showed resistance to
      imipenem. Carbapenemases genes detected in our study were as follows: blaOXA-48
      (84 isolates), blaNDM-1 (8 isolates), blaOXA-48 + blaVIM (5 isolates), and blaOXA
      48 + blaNDM-1 (5 isolates). Our research provides epidemiological data showing
      the quick spread of carbapenem-resistant bacteria in our region, which calls for
      new surveillance strategies and strict hygiene rules.

PMID- 29596034
TI  - Postdischarge Correlates of Health Literacy Among Medicaid Inpatients.
AB  - Health literacy may represent a target for intervention to improve hospital
      transitions. This study analyzed the association of health literacy with
      postdischarge utilization among Medicaid patients treated in an integrated health
      care system. Discharged inpatients covered by Medicaid (N = 112) participated in
      this observational study set in a single 600-bed hospital in a private,
      nonprofit, integrated health care system in the southwestern United States.
      Participants completed surveys within 15 days of discharge, self-reporting
      demographics, self-care behaviors, and 2 measures of health literacy (REALM-SF
      [Short Form of the Rapid Estimate of Adult Literacy in Medicine] and Chew [health
      literacy screen from Chew et al]). Electronic medical records data were
      incorporated to determine occurrence of 30-day/90-day postdischarge emergency
      visits and readmission. Half the respondents (54%) scored at the high-school
      grade equivalent on REALM-SF, while 46% scored adequate health literacy on the
      Chew. Forty percent (40%) experienced either emergency care or readmission within
      90 days post discharge. Patients who were younger, female, or living with
      children had relatively better health literacy. Health literacy itself was not
      associated with readmission or postdischarge emergency care, although African
      American race was. Although Medicaid patients varied considerably on health
      literacy, this factor was not associated with adverse health care outcomes.
      Future work should better identify individuals requiring supportive transition
      services to reduce problems following hospital discharge.

PMID- 29596035
TI  - Functional status predicts acute care readmission in the traumatic spinal cord
      injury population.
AB  - Context/objective Acute care readmission has been identified as an important
      marker of healthcare quality. Most previous models assessing risk prediction of
      readmission incorporate variables for medical comorbidity. We hypothesized that
      functional status is a more robust predictor of readmission in the spinal cord
      injury population than medical comorbidities. Design Retrospective cross
      sectional analysis. Setting Inpatient rehabilitation facilities, Uniform Data
      System for Medical Rehabilitation data from 2002 to 2012 Participants traumatic
      spinal cord injury patients. Outcome measures A logistic regression model for
      predicting acute care readmission based on demographic variables and functional
      status (Functional Model) was compared with models incorporating demographics,
      functional status, and medical comorbidities (Functional-Plus) or models
      including demographics and medical comorbidities (Demographic-Comorbidity). The
      primary outcomes were 3- and 30-day readmission, and the primary measure of model
      performance was the c-statistic. Results There were a total of 68,395 patients
      with 1,469 (2.15%) readmitted at 3 days and 7,081 (10.35%) readmitted at 30 days.
      The c-statistics for the Functional Model were 0.703 and 0.654 for 3 and 30 days.
      The Functional Model outperformed Demographic-Comorbidity models at 3 days (c
      statistic difference: 0.066-0.096) and outperformed two of the three Demographic
      Comorbidity models at 30 days (c-statistic difference: 0.029-0.056). The
      Functional-Plus models exhibited negligible improvements (0.002-0.010) in model
      performance compared to the Functional models. Conclusion Readmissions are used
      as a marker of hospital performance. Function-based readmission models in the
      spinal cord injury population outperform models incorporating medical
      comorbidities. Readmission risk models for this population would benefit from the
      inclusion of functional status.

PMID- 29596036
TI  - Provider Perspectives on the Collection of Social Determinants of Health.
AB  - Social determinants of health (SDH) impact health outcomes. Medical centers have
      begun to collect SDH data, urged by government and scientific entities. Provider
      perspectives on collecting SDH are unknown. The aim is to understand differences
      in views and preferences according to provider characteristics. A cross-sectional
      survey of University of Miami clinical faculty was conducted in late 2016. The
      survey contained 11 questions: 8 demographic and departmental responsibilities
      questions and 3 Likert scale questions to capture collection and use of SDH
      perspectives. The main outcome was whether providers thought the benefit of
      collecting SDH outweighs the burden and risks. In all, 240 faculty members were
      included. The majority were men (64%), with a mean age of 51 years. Among
      participants, 53.5% were non-Hispanic white, 32% were Hispanic, 5% were
      Black/African American, and 5% were Asian. The majority agreed that SDH are
      important predictors of health outcomes and quality of care (83%). When comparing
      minority to nonminority faculty, 25% believed that SDH should only be available
      to PCPs, compared to 8% of nonminorities (P < 0.01). In a multivariate model,
      belonging to a racial ethnic minority was the only characteristic associated with
      believing that benefits of collecting SDH outweigh the risks (odds ratio 1.87,
      95% confidence interval 1.02- 3.5) after adjusting for age, sex, minority status,
      health care provider type, type of responsibilities, and department. This study
      reveals that although most providers of a health system believe social risks
      impact health outcomes and quality metrics, the buy-in to collect SDH varies
      according to the racial/ethnic composition of the faculty.

PMID- 29596037
TI  - Tissue Engineering Under Microgravity Conditions-Use of Stem Cells and
      Specialized Cells.
AB  - Experimental cell research studying three-dimensional (3D) tissues in space and
      on Earth using new techniques to simulate microgravity is currently a hot topic
      in Gravitational Biology and Biomedicine. This review will focus on the current
      knowledge of the use of stem cells and specialized cells for tissue engineering
      under simulated microgravity conditions. We will report on recent advancements in
      the ability to construct 3D aggregates from various cell types using devices
      originally created to prepare for spaceflights such as the random positioning
      machine (RPM), the clinostat, or the NASA-developed rotating wall vessel (RWV)
      bioreactor, to engineer various tissues such as preliminary vessels, eye tissue,
      bone, cartilage, multicellular cancer spheroids, and others from different cells.
      In addition, stem cells had been investigated under microgravity for the purpose
      to engineer adipose tissue, cartilage, or bone. Recent publications have
      discussed different changes of stem cells when exposed to microgravity and the
      relevant pathways involved in these biological processes. Tissue engineering in
      microgravity is a new technique to produce organoids, spheroids, or tissues with
      and without scaffolds. These 3D aggregates can be used for drug testing studies
      or for coculture models. Multicellular tumor spheroids may be interesting for
      radiation experiments in the future and to reduce the need for in vivo
      experiments. Current achievements using cells from patients engineered on the RWV
      or on the RPM represent an important step in the advancement of techniques that
      may be applied in translational Regenerative Medicine.

PMID- 29596038
TI  - Visual Memories Bypass Normalization.
AB  - How distinct are visual memory representations from visual perception? Although
      evidence suggests that briefly remembered stimuli are represented within early
      visual cortices, the degree to which these memory traces resemble true visual
      representations remains something of a mystery. Here, we tested whether both
      visual memory and perception succumb to a seemingly ubiquitous neural
      computation: normalization. Observers were asked to remember the contrast of
      visual stimuli, which were pitted against each other to promote normalization
      either in perception or in visual memory. Our results revealed robust
      normalization between visual representations in perception, yet no signature of
      normalization occurring between working memory stores-neither between
      representations in memory nor between memory representations and visual inputs.
      These results provide unique insight into the nature of visual memory
      representations, illustrating that visual memory representations follow a
      different set of computational rules, bypassing normalization, a canonical visual
      computation.

PMID- 29596039
TI  - Subclassification of Bethesda Atypical and Follicular Neoplasm Categories
      According to Nuclear and Architectural Atypia Improves Discrimination of Thyroid
      Malignancy Risk.
AB  - BACKGROUND: Although The Bethesda System for Reporting Thyroid Cytopathology has
      provided clinicians with a standardized classification scheme for the diagnosis
      of thyroid fine-needle aspiration cytology (FNAC) specimens, the indeterminate
      categories of Bethesda III (B3)-atypia of undetermined significance/follicular
      lesion of undetermined significance (AUS/FLUS)-and Bethesda IV (B4)-follicular
      neoplasm/suspicious for follicular neoplasm (FN/SFN)-continue to pose challenges
      with regards to ideal diagnostic and therapeutic management. Having previously
      demonstrated the presence of nuclear atypia as a high-risk subgroup in B3, the
      objective of this study was to evaluate the malignancy rates in the B4 subgroup
      with nuclear atypia. METHODS: A retrospective review of all thyroid FNACs
      diagnosed as B4 (FN/SFN) between 2008 and 2015 was conducted at a tertiary
      referral center in Singapore. Data on patient demographics, sonographic features,
      and final histological diagnosis were collected. This was compared to data from a
      previous analysis on all nodules diagnosed as B3 (AUS/FLUS) over a similar
      period. RESULTS: A total of 137/309 (44.3%) and 88/111 (79.3%) FNACs diagnosed as
      B3 and B4, respectively, underwent surgical excision yielding final
      histopathological diagnoses. The malignancy rate of B4 was 31/88 (35.2%) compared
      to B3, which was 37/137 (27.0%). Subclassification based on the presence of
      architectural versus nuclear atypia showed significantly higher malignancy rates
      in B4 nodules with nuclear atypia (21.8% vs. 57.6%; p < 0.01). These findings
      corroborate previous results within the B3 category (malignancy rate of 14.7% vs.
      36.8%; p < 0.01). The only sonographic features predictive of malignancy were the
      presence of macrocalcifications in B4 compared to irregularity of margins in B3.
      CONCLUSION: The presence of nuclear atypia identifies subgroups with significant
      differential malignancy risks within both the B3 and B4 categories. This supports
      the notion that subclassification is a useful risk stratification tool that can
      guide diagnostic and therapeutic management of indeterminate thyroid nodules with
      heterogenous risk profiles.

PMID- 29596040
TI  - Comparative Study of Drainage and Antibiotics versus Drainage Only in the
      Management of Primary Subcutaneous Abscesses.
AB  - BACKGROUND: Skin and soft tissue infections are common problems dealt with in
      emergency departments and medical offices. It is routine practice to prescribe
      antibiotic agents after incision and drainage of cutaneous abscesses. However,
      current evidence does not support prescribing oral antibiotic agents after
      surgical debridement. The aim of the present study was to determine the actual
      role of antibiotic agents after drainage of cutaneous abscesses. PATIENTS AND
      METHODS: This was a prospective study of patients undergoing incision and
      drainage (I&D) of a subcutaneous abscess. Patients were randomly assigned either
      to receive antibiotic agents (group 1) or placebo (group 2) after I&D. The
      primary end point was resolution rate of the abscess at the seventh day.
      Secondary end points were pain at the seventh day and total time to full healing
      of the wound. P value <0.05 was considered statistically significant. RESULTS:
      One hundred sixty-five patients were included for analysis. Age, gender, body
      mass index (BMI), and comorbidities did not differ substantially between groups.
      Chest and peri-anal abscesses were statistically more frequent in group 2,
      whereas neck abscesses were more frequent in group 1 (p = 0.02). Leukocyte count
      was also statistically higher in group 1 (p = 0.005). Resolution rate was 96% in
      group 1 and 93% in group 2, with no statistical difference between both (p =
      0.28). Neither pain at seventh day nor time to full healing differed
      statistically between groups. CONCLUSIONS: Antibiotic agents are not necessary
      for uncomplicated subcutaneous abscesses after I&D. These cases can be managed
      safely on an outpatient basis without any increase in morbidity.

PMID- 29596041
TI  - Implementing Outcome Measures in Palliative Care.

PMID- 29596042
TI  - Ten Tips Nephrologists Wish the Palliative Care Team Knew About Caring for
      Patients with Kidney Disease.
AB  - Many patients with chronic kidney disease (CKD) and end-stage renal disease have
      unmet palliative care (PC) needs. Physical and emotional symptoms are common.
      Some, like uremia and fluid overload, improve with dialysis, but the increasing
      age of patients initiating renal replacement therapy leaves many untreatable
      comorbidities like dementia and frailty to negatively impact quality of life.
      Written by nephrologists and PC clinicians, this article will help PC providers
      to have a richer understanding of kidney disease-related symptom burden, disease
      trajectory, prognosis, and barriers to hospice enrollment for patients with CKD
      and end-stage renal disease.

PMID- 29596043
TI  - Sex-Specific Associations Between Complement Component 3 and Component 4 Levels
      and Metabolic Syndrome in an Adult Population.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a cluster of cardiovascular and
      metabolic risk factors in the same individual. Inflammation has been reported to
      be directly involved in the development of metabolic disease. Complement
      component 3 (C3) and complement component 4 (C4) have been identified as
      important inflammatory markers relevant to metabolic disease. However, few
      studies have analyzed the association between C3 and/or C4 and MetS. In this
      study, our aim is to evaluate sex-specific association between C3 and C4 levels
      and risk of MetS in an adult population. METHODS: A cohort of 4635 adults was
      followed from 2010 to 2016. Serum C3 and C4 levels were measured using an
      immunonephelometric technique. MetS was defined by the American Heart Association
      scientific statements of 2009. Cox proportional hazard regression models were
      used to assess sex-specific association between C3 and C4 levels and the
      incidence of MetS. RESULTS: During the ~6 years of follow-up, 1445 new cases of
      MetS were identified. After being adjusted to confounding factors, the hazard
      ratios (95% confidence interval) of MetS for gradually increasing quintiles of C3
      were 1.00, 1.23 (0.98-1.54), 1.50 (1.21-1.87), 1.64 (1.32-2.04), and 1.75 (1.41
      2.18) (P for trend <0.0001) in men and 1.00, 0.96 (0.60-1.53), 1.61 (1.06-2.44),
      2.01 (1.34-3.03), and 2.43 (1.63-3.63) (P for trend <0.0001) in women,
      respectively. Similar results were also obtained for gradually increasing
      quintiles of C4 in women, but not in men. CONCLUSIONS: The levels of C3 were
      significantly associated with the incidence of MetS in both men and women. The
      levels of C4 contributed to risk of MetS only in women.

PMID- 29596044
TI  - The Effects of High-Protein and High-Monounsaturated Fat Meals on Postprandial
      Lipids, Lipoprotein Particle Numbers, Cytokines, and Leptin Responses in
      Overweight/Obese Subjects.
AB  - BACKGROUND: Obesity is linked to dyslipidemia, proinflammatory state, and
      hyperleptinemia. The influence of high-protein (HP) versus high-monounsaturated
      fat (HMF) meals on postprandial lipids, lipoprotein particle numbers, cytokines,
      and leptin responses in overweight/obese (OW/O) subjects is unknown. METHODS:
      Twenty-four OW/O participants consumed an HP (31.9% energy from protein) and HMF
      (35.2% fat and 20.7% monounsaturated fat) meal, of similar energy/carbohydrate
      content, in a random order. The outcome variables were assessed from blood
      samples collected in fasted and postprandial (3 hr) states. RESULTS: Repeated
      measures analysis found significant (P < 0.05) meal condition by time
      interactions for triglycerides (TGs), very low-density lipoprotein particles
      (VLDLP), total high-density lipoprotein particles (T-HDLP), and the ratio of
      large-buoyant high-density lipoprotein 2b (LB-HDL2b) to T-HDLP, and meal effect
      on small-dense HDLP (SD-HDLP). Comparison of HP versus HMF condition showed
      significantly lower TG at 120 min [geometric mean (95% confidence interval, CI):
      148 (125-175) vs. 194 (164-230) mg/dL] and 180 min [167 (138-203) vs. 230 (189
      278) mg/dL] and VLDLP at 180 min [70.0 (58.2-84.3) vs. 88.0 (73.1-106) nmol/L].
      HP versus HMF condition showed significantly lower LB-HDL2b/T-HDLP at 180 min
      [mean difference (95% CI): 0.021 (0.004-0.038)], and higher T-HDLP [671 (263
      1079) nmol/L] and SD-HDLP [606 (292-920) nmol/L] at 120 min. Area under the curve
      was significantly lower for TG and higher for T-HDLP, SD-HDLP, and small-dense
      LDL III (SD-LDL III) in the HP condition. Cytokines and leptin were not different
      between conditions. CONCLUSION: OW/O subjects had lower TG and VLDLP, but less
      favorable SD-LDL III, SD-HDLP, and LB-HDL2b/T-HDLP ratio responses to the HP
      versus HMF meals.

PMID- 29596045
TI  - Positive behaviour support training for staff for treating challenging behaviour
      in people with intellectual disabilities: a cluster RCT.
AB  - BACKGROUND: Preliminary studies have indicated that training staff in Positive
      Behaviour Support (PBS) may help to reduce challenging behaviour among people
      with intellectual disability (ID). OBJECTIVE: To evaluate whether or not such
      training is clinically effective in reducing challenging behaviour in routine
      care. The study also included longer-term follow-up (approximately 36 months).
      DESIGN: A multicentre, single-blind, two-arm, parallel-cluster randomised
      controlled trial. The unit of randomisation was the community ID service using an
      independent web-based randomisation system and random permuted blocks on a 1 : 1
      allocation stratified by a staff-to-patient ratio for each cluster. SETTING:
      Community ID services in England. PARTICIPANTS: Adults (aged > 18 years) across
      the range of ID with challenging behaviour [>= 15 Aberrant Behaviour Checklist -
      Community total score (ABC-CT)]. INTERVENTIONS: Manual-assisted face-to-face PBS
      training to therapists and treatment as usual (TAU) compared with TAU only in the
      control arm. MAIN OUTCOME MEASURES: Carer-reported changes in challenging
      behaviour as measured by the ABC-CT over 12 months. Secondary outcomes included
      psychopathology, community participation, family and paid carer burden, family
      carer psychopathology, costs of care and quality-adjusted life-years (QALYs).
      Data on main outcome, service use and health-related quality of life were
      collected for the 36-month follow-up. RESULTS: A total of 246 participants were
      recruited from 23 teams, of whom 109 were in the intervention arm (11 teams) and
      137 were in the control arm (12 teams). The difference in ABC-CT between the
      intervention and control arms [mean difference -2.14, 95% confidence interval
      (CI) -8.79 to 4.51; p = 0.528] was not statistically significant. No treatment
      effects were found for any of the secondary outcomes. The mean cost per
      participant in the intervention arm was L1201. Over 12 months, there was a
      difference in QALYs of 0.076 in favour of the intervention (95% CI 0.011 to 0.140
      QALYs) and a 60% chance that the intervention is cost-effective compared with TAU
      from a health and social care cost perspective at the threshold of L20,000 per
      QALY gained. Twenty-nine participants experienced 45 serious adverse events
      (intervention arm, n = 19; control arm, n = 26). PBS plans were available for 33
      participants. An independent assessment of the quality of these plans found that
      all were less than optimal. Forty-six qualitative interviews were conducted with
      service users, family carers, paid carers and service managers as part of the
      process evaluation. Service users reported that they had learned to manage
      difficult situations and had gained new skills, and carers reported a positive
      relationship with therapists. At 36 months' follow-up (n = 184), the mean ABC-CT
      difference between arms was not significant (-3.70, 95% CI -9.25 to 1.85; p =
      0.191). The initial cost-effectiveness of the intervention dissipated over time.
      LIMITATIONS: The main limitations were low treatment fidelity and reach of the
      intervention. CONCLUSIONS: Findings from the main study and the naturalistic
      follow-up suggest that staff training in PBS as delivered in this study is
      insufficient to achieve significant clinical gains beyond TAU in community ID
      services. Although there is an indication that training in PBS is potentially
      cost-effective, this is not maintained in the longer term. There is increased
      scope to develop new approaches to challenging behaviour as well as optimising
      the delivery of PBS in routine clinical practice. TRIAL REGISTRATION: This study
      is registered as NCT01680276. 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. 15. See
      the NIHR Journals Library website for further project information.

PMID- 29596048
TI  - Intimate Partner Violence and Uptake of Antenatal Care: A Scoping Review of Low-
      and Middle-Income Country Studies.
AB  - CONTEXT: Intimate partner violence (IPV) is associated with negative physical and
      mental health outcomes. Antenatal care can act as a link to IPV services, but
      experiencing IPV may be associated with reduced uptake of antenatal care, an
      issue that has received little attention from researchers. METHODS: A scoping
      review was conducted to synthesize quantitative research on IPV and uptake of
      antenatal care in low-resource settings. Keyword searches of PubMed and other
      databases and snowball searches of reference lists were conducted to identify
      articles published in 2005-2015 that measured one or more types of IPV (physical,
      sexual or emotional) or controlling behavior and assessed the relationship of
      such abuse with use of antenatal care. For each identified article, key
      characteristics and findings were abstracted, and study quality was assessed.
      RESULTS: Sixteen articles, representing 10 low- and middle-income countries, met
      the inclusion criteria. Most studies were of medium-to-high quality but low
      rigor, reflecting the abundance of cross-sectional studies in the literature. In
      all 16 studies, IPV was negatively associated with initiation of antenatal care,
      number of visits or use of a skilled provider. Analyses revealed reduced odds of
      antenatal care use among women who had experienced IPV (odds ratios, 0.5-0.8) and
      elevated odds of antenatal care use among women who had not experienced IPV or of
      nonuse among women who had experienced IPV (1.2-4.1). CONCLUSION: Women in low
      resource settings who experience IPV have a reduced likelihood of obtaining
      optimal antenatal care and may benefit from interventions to mitigate barriers to
      care.

PMID- 29596049
TI  - Metadata Correction: Mobile Phone Ownership Is Not a Serious Barrier to
      Participation in Studies: Descriptive Study.
AB  - [This corrects the article DOI: 10.2196/mhealth.8123.].

PMID- 29596046
TI  - Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by
      human insulin degrading enzyme.
AB  - Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in
      type two diabetes, Alzheimer's, inflammation, and other human diseases. However,
      the process through which IDE recognizes peptides that tend to form amyloid
      fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin
      bound dimeric IDE states, revealing that IDE displays a large opening between the
      homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture
      based on size and charge complementarity. We also used cryoEM, X-ray
      crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how
      amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby
      inducing selective degradation by substrate-assisted catalysis. Furthermore, our
      insulin-bound IDE structures explain how IDE processively degrades insulin by
      stochastically cutting either chain without breaking disulfide bonds. Together,
      our studies provide a mechanism for how IDE selectively degrades amyloidogenic
      peptides and offers structural insights for developing IDE-based therapies.

PMID- 29596047
TI  - Oligodendrocytes control potassium accumulation in white matter and seizure
      susceptibility.
AB  - The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and
      deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role
      of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in
      white matter has not been defined. Here, we show that selective deletion of
      Kir4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not
      impair their development or disrupt the structure of myelin. However, mice
      lacking oligodendrocyte Kir4.1 channels exhibited profound functional
      impairments, including slower clearance of extracellular K+ and delayed recovery
      of axons from repetitive stimulation in white matter, as well as spontaneous
      seizures, a lower seizure threshold, and activity-dependent motor deficits. These
      results indicate that Kir4.1 channels in oligodendrocytes play an important role
      in extracellular K+ homeostasis in white matter, and that selective loss of this
      channel from oligodendrocytes is sufficient to impair K+ clearance and promote
      seizures.

PMID- 29596050
TI  - Testing for HbA1c, in addition to the oral glucose tolerance test, in screening
      for abnormal glucose regulation helps to reveal patients with early beta-cell
      function impairment.
AB  - BACKGROUND: The oral glucose tolerance test (OGTT) is recommended to screen for
      diabetes in patients with coronary artery disease. We hypothesized that testing
      for glycated hemoglobin (HbA1c), in addition to the OGTT, in screening for
      abnormal glucose regulation may help to reveal patients with beta-cell function
      impairment. METHODS: Patients with no history of diabetes who were admitted for
      coronary angiography were recruited to undergo an OGTT and HbA1c test 2-4 weeks
      after hospital discharge. beta-cell function and insulin resistance were assessed
      using the homeostasis model assessment (HOMA-beta and HOMA-IR, respectively). For
      patients with normal glucose tolerance (NGT) based on the OGTT, we compared HOMA
      beta between two subgroups of patients using an HbA1c cutoff of 39 mmol/mol or 42
      mmol/mol. For patients with prediabetes based on an OGTT, we compared the HOMA
      beta between two subgroups of patients using an HbA1c cutoff of 48 mmol/mol.
      RESULTS: A total of 1044 patients were analyzed. In patients with NGT by OGTT
      (n=432), those with an HbA1c >=42 mmol/mol had a lower HOMA-beta compared to
      those with an HbA1c <42 mmol/mol (107+/-82 vs. 132+/-96, p=0.018). In patients
      with prediabetes by OGTT (n=423), those with an HbA1c >=48 mmol/mol had a lower
      HOMA-beta compared to those with an HbA1c <48 mmol/mol (91+/-52 vs. 120+/-88,
      p=0.003). No significant between-group difference in HOMA-IR was noted.
      CONCLUSIONS: The use of HbA1c in addition to the OGTT in screening for abnormal
      glucose regulation helped to reveal patients with early beta-cell function
      impairment.

PMID- 29596051
TI  - Harmonization initiatives in the generation, reporting and application of
      biological variation data.

PMID- 29596052
TI  - The impact of mild hypercholesterolemia on glycemic and hormonal profiles,
      menstrual characteristics and the ovarian morphology of women with polycystic
      ovarian syndrome.
AB  - Background The severity of polycystic ovarian syndrome (PCOS) has been clearly
      associated with insulin resistance, obesity and metabolic syndrome. The purpose
      of the present cross-sectional study is to investigate whether mild
      hypercholesterolemia alters the biochemical and clinical profile of PCOS
      patients. Methods Our study is based on a prospectively collected population of
      women of reproductive age who were diagnosed with PCOS according to the
      definition of the Rotterdam European Society of Human Reproduction and
      Embryology/American Society for Reproductive Medicine (ASRM/ESHRE) criteria. For
      the correlation analysis we used the non-parametric Spearman's rank correlation
      coefficient. Partial correlation was also performed to control for potential
      confounders observed in the univariate analysis. Results Overall, 235 patients
      were included. Their mean age ranged between 14 and 45 years old and the body
      mass index (BMI) between 17 and 54. Women with mild hypercholesterolemia had a
      higher BMI and their fasting insulin was increased as well as indices of insulin
      resistance [Homeostatic model assessment (HOMA), quantitative insulin sensitivity
      check index (QUICKI), Matsuda index] compared to women with PCOS with normal
      cholesterol levels. Correlation statistics suggested that the effect of serum
      lipids on the hormonal profile of patients was weak. Both low-density lipoprotein
      (LDL) and high-density lipoprotein (HDL) exerted a significant mild negative
      correlation to glucose and insulin. However, after controlling the results for
      BMI and age (the two variables that were found significantly different in the
      univariate analysis) we observed that this effect was non-significant. Conclusion
      Mild hypercholesterolemia does not affect the hormonal profile of patients with
      PCOS; hence, to date, there is no evidence to suggest its treatment for the
      correction of menstrual and hormonal abnormalities in PCOS women.

PMID- 29596054
TI  - Antimicrobial properties of terrestrial snail and slug mucus.

PMID- 29596053
TI  - The "adipose tissue expandability" hypothesis: a potential mechanism for insulin
      resistance in obese youth.
AB  - Obesity has become a major global health challenge of the 21st century, as it is
      associated with the onset of type 2 diabetes (T2D) and cardiovascular
      complications, even at a very early age in life. The root causes of pediatric
      obesity remain incompletely understood. The obesity epidemic together with the
      relationship of obesity to the growing population burden of chronic disease
      presents unprecedented research opportunities and challenges. Decades of obesity
      related research funded by governments around the world have yielded many
      important discoveries about both etiological pathways and preventive or
      therapeutic interventions. Yet, there is a sense that the problem is outpacing
      these research efforts. Obesity poses a significant risk for the development of
      cardiovascular disease (CVD) , diabetes and certain cancers thereby shortening
      life expectancy. Nevertheless, many obese individuals do not develop any of these
      comorbidities. One hypothesis explaining this dilemma is that total body fat is
      not the culprit of adverse health in obesity rather the relative proportion of
      lipids in various fat depots is what determines the metabolic risk. In this
      review, we describe the role of altered fat partitioning in youth onset obesity
      and its relation to fatty liver and T2D during adolescence.

PMID- 29596055
TI  - Specifications of Standards in Systems and Synthetic Biology: Status and
      Developments in 2017.
AB  - Standards are essential to the advancement of Systems and Synthetic Biology.
      COMBINE provides a formal body and a centralised platform to help develop and
      disseminate relevant standards and related resources. The regular special issue
      of the Journal of Integrative Bioinformatics aims to support the exchange,
      distribution and archiving of these standards by providing unified, easily
      citable access. This paper provides an overview of existing COMBINE standards and
      presents developments of the last year.

PMID- 29596056
TI  - Research for the lichen Usnea barbata metabolites.
AB  - This work presents investigations of biologically active metabolites of Usnea
      barbata lichen. Extraction conditions for usnic acid and other biologically
      active phytocomponents using various solvent systems were chosen. Modern
      analytical techniques were used to study composition of the obtained extracts;
      usnic acid and phenolic compound contents were estimated. Antioxidant activity
      and antimicrobial properties of lichen dry extract against bacteria Bacillus
      subtilis and Pseudomonas fluorescens were studied.

PMID- 29596057
TI  - Light controllable catalytic activity of Au clusters decorated with photochromic
      molecules.
AB  - By ab initio calculations, we show that when decorated with a photochromic
      molecule, the catalytic activity of an Au nanocluster can be reversibly
      controlled by light. The combination of a photochromic thiol-pentacarbonyl
      azobenzene (TPA) molecule and an Au8 cluster is chosen as a model catalyst. The
      TPA molecule has two configurations (trans and cis) that can be reversibly
      converted to each other upon photo-excitation. Our calculations show that when
      the TPA takes the trans configuration, the combined system (trans-Au8) is an
      excellent catalyst for CO oxidation. The reaction barrier of the catalyzed CO
      oxidation is less than 0.4 eV. While, the reaction barrier of CO oxidation
      catalyzed by cis-Au8 is very high (>2.7 eV), indicating that the catalyst is
      inactive. These results pave the way for a new class of light controllable
      nanoscale catalysts.

PMID- 29596058
TI  - Manipulating the assembly of perovskites onto soft nanoimprinted titanium dioxide
      templates.
AB  - Soft nanoimprinted titanium dioxide (TiO2) substrates decorated with
      methylammonium lead halide perovskite (MAPbI3) crystals were fabricated by
      controlling the perovskite precursor concentration and volume during spin coat
      processing combined with the use of hydrophobic TiO2 templates. The patterned
      growth was demonstrated with different perovskite crystallization methods. We
      investigated and successfully demonstrated the controlled assembly of two MAPbI3
      nanomaterials, one a nanocomposite formed between the perovskite and a hole
      conducting polymer poly(2,5-bis(N-methyl-N-hexylamino)phenylene vinylene)
      (BAMPPV), and a second formed from perovskite crystals using common solution
      based MAPbI3 growth methods (1-step and 2-step processing). Both types of MAPbI3
      crystals were fabricated on hydrophobic TiO2 nanotemplates composed of nanowells
      or grating patterns. Patterned areas as large as 100 MUm * 100 MUm were achieved.
      We examined and characterized the substrates using atomic force microscopy,
      scanning electron microscopy, x-ray diffraction, and energy dispersive
      spectroscopy. We present the optical properties (i.e. fluorescence and
      transmission) of soft nanoimprinted nanowells decorated with perovskites
      demonstrating the successful synthesis of MAPbI3 perovskite nanocrystals. As an
      example of their use, we demonstrate a two terminal device and show photocurrent
      response of a perovskite patterned micro-grating. Our method is a nondestructive
      approach to nanopatterning perovskites, and produces patterned arrays that
      maintain their photo-electric properties. The results presented herein suggests
      an attractive route to developing nanopatterned and small area perovskite
      substrates for applications in photovoltaics, x-ray sensing/detection, image
      sensor arrays, and others.

PMID- 29596059
TI  - A brain-age model for preterm infants based on functional connectivity.
AB  - OBJECTIVE: In this study, the development of EEG functional connectivity during
      early development has been investigated in order to provide a predictive age
      model for premature infants. APPROACH: The functional connectivity has been
      assessed via the coherency function (its imaginary part (ImCoh) and its mean
      squared magnitude (MSC)), the phase locking value ([Formula: see text]) and the
      Hilbert-Schimdt dependence (HSD) in a dataset of 30 patients, partially described
      and employed in previous studies (Koolen et al 2016 Neuroscience 322 298-307;
      Lavanga et al 2017 Complexity 2017 1-13). Infants' post-menstrual age (PMA)
      ranges from 27 to 42 weeks. The topology of the EEG couplings has been
      investigated via graph-theory indices. MAIN RESULTS: Results show a sharp
      decrease in ImCoh indices in theta, (4-8) Hz and alpha, (8-16) Hz bands and MSC
      in beta, (16-32) Hz band with maturation, while a more modest positive
      correlation with PMA is found for HSD, [Formula: see text] and MSC in [Formula:
      see text], theta, alpha bands. The best performances for the PMA prediction were
      mean absolute error equal to 1.51 weeks and adjusted coefficient of determination
      [Formula: see text] equal to 0.8. SIGNIFICANCE: The reported findings suggest a
      segregation of the cortex connectivity, which favours a diffused tasks
      architecture on the brain scalp. In summary, the results indicate that the
      neonates' brain development can be described via lagged-interaction network
      features.

PMID- 29596060
TI  - Antibacterial activity and inflammation inhibition of ZnO nanoparticles embedded
      TiO2 nanotubes.
AB  - Titanium (Ti) with nanoscale structure on the surface exhibits excellent
      biocompatibility and bone integration. Once implanted, the surgical implantation
      may lead to bacterial infection and inflammatory reaction, which cause the
      implant failure. In this work, irregular and nanorod-shaped ZnO nanoparticles
      were doped into TiO2 nanotubes (TNTs) with inner diameter of about 50 nm by
      electro-deposition. The antibacterial properties of ZnO incorporated into TiO2
      nanotubes (TNTs/ZnO) were evaluated using Staphylococcus aureus (S. aureus). Zn
      ions released from the nanoparticles and the morphology could work together,
      improving antibacterial effectiveness up to 99.3% compared with the TNTs.
      Macrophages were cultured on the samples to determine their respective anti
      inflammatory properties. The proliferation and viability of macrophages were
      evaluated by the CCK-8 method and Live&Dead stain, and the morphology of the
      cells was observed by scanning electron microscopy. Results indicated that
      TNTs/ZnO has a significant inhibitory effect on the proliferation and adhesion of
      macrophages, which could be used to prevent chronic inflammation and control the
      inflammatory reaction. Besides, the release of Zn ions from the ZnO nanoparticles
      is a long-term process, which could be beneficial for bone integration. Results
      demonstrate that ZnO deposited into TNTs improved the antibacterial effectiveness
      and weakened the inflammatory reaction of titanium-based implants, which is a
      promising approach to enhance their bioactivity.

PMID- 29596061
TI  - Effect of magnetization boundary condition on cavity magnon polariton of YIG thin
      film.
AB  - Motivated by recent studies of cavity magnon polariton (CMP), we extended a
      previous theoretical work to generalize microwave transmission calculation with
      various magnetization boundary condition of YIG thin film embedded in cavity. It
      is found that numerical implementation given in this paper can be easily applied
      to other magnetization boundary condition and extended to magnetic multilayers.
      Numerical results show that ferromagnetic resonance mode of microwave
      transmission spectrum, which is absent in previous calculation, can be recovered
      by altering the pinning condition of surface spins. The demonstrated reliability
      of our theory opens attractive perspectives for studying CMP of thin film with
      complicated surface magnetization distribution and magnetic multilayers.

PMID- 29596062
TI  - Imaging activated T cells predicts response to cancer vaccines.
AB  - In situ cancer vaccines are under active clinical investigation, given their
      reported ability to eradicate both local and disseminated malignancies.
      Intratumoral vaccine administration is thought to activate a T cell-mediated
      immune response, which begins in the treated tumor and cascades systemically. In
      this study, we describe a PET tracer (64Cu-DOTA-AbOX40) that enabled noninvasive
      and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We
      report the spatiotemporal dynamics of T cell activation following in situ
      vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We
      demonstrate that OX40 imaging was able to predict tumor responses on day 9 after
      treatment on the basis of tumor tracer uptake on day 2, with greater accuracy
      than both anatomical and blood-based measurements. These studies provide key
      insights into global T cell activation following local CpG treatment and indicate
      that 64Cu-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer
      immunotherapy strategies.

PMID- 29596065
TI  - Reversible Visual Field Defect After Isolated Intraventricular Hemorrhage.

PMID- 29596063
TI  - Neuronal hypothalamic regulation of body metabolism and bone density is galanin
      dependent.
AB  - In the brain, the ventral hypothalamus (VHT) regulates energy and bone
      metabolism. Whether this regulation uses the same or different neuronal circuits
      is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure,
      glucose utilization, and bone density, yet the specific neurons responsible for
      each or all of these phenotypes are not identified. Using neuron-specific,
      genetically targeted AP1 alterations as a tool in adult mice, we found that
      agouti-related peptide-expressing (AgRP-expressing) or proopiomelanocortin
      expressing (POMC-expressing) neurons, predominantly present in the arcuate
      nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose
      utilization, and bone formation and density, although their effects on bone
      resorption differed. In contrast, AP1 alterations in steroidogenic factor 1
      expressing (SF1-expressing) neurons, present in the ventromedial hypothalamus
      (VMH), increase energy but decrease bone density, suggesting that these effects
      are independent. Altered AP1 signaling also increased the level of the
      neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin
      silencing using shRNA) or pharmacological galanin receptor blockade counteracted
      the observed effects on energy and bone. Thus, AP1 antagonism reveals that AgRP-
      and POMC-expressing neurons can stimulate body metabolism and increase bone
      density, with galanin acting as a central downstream effector. The results
      obtained with SF1-expressing neurons, however, indicate that bone homeostasis is
      not always dictated by the global energy status, and vice versa.

PMID- 29596064
TI  - Contributions of inflammation and tumor microenvironment to neurofibroma
      tumorigenesis.
AB  - Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell
      tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is
      mast cell infiltration, which is recruited by chemoattractant stem cell factor
      (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the
      present study, we use new, genetically engineered Scf mice to decipher the
      contributions of tumor-derived SCF and mast cells to neurofibroma development. We
      demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann
      cells. However, removal of mast cells by depleting the main SCF source only
      slightly affects neurofibroma progression. Other inflammation signatures show
      that all neurofibromas are associated with high levels of macrophages regardless
      of Scf status. These findings suggest an active inflammation in neurofibromas and
      partly explain why mast cell removal alone is not sufficient to relieve tumor
      burden in this experimental neurofibroma model. Furthermore, we show that
      plexiform neurofibromas are highly associated with injury-prone spinal nerves
      that are close to flexible vertebras. In summary, our study details the role of
      inflammation in neurofibromagenesis. Our data indicate that prevention of
      inflammation and possibly also nerve injury at the observed tumor locations are
      therapeutic approaches for neurofibroma prophylaxis and that such treatment
      should be explored.

PMID- 29596066
TI  - Sudden Unexpected Death in Epilepsy: Incidence, Risk Factors, and Proposed
      Mechanisms.
AB  - Epilepsy is a common neurological disorder associated with increased morbidity
      and mortality, including premature death from different causes. Sudden unexpected
      death in epilepsy, or SUDEP, is one of the most common causes of death in people
      with epilepsy and originally brought to light by medical examiners. It accounts
      for 5% to 30% of all deaths in individuals with epilepsy and up to 50% in
      individuals with medically refractory epilepsy. It is commonly associated with a
      history of generalized tonic-clonic seizures and may be mitigated by other
      electroclinical risk factors, such as postictal electroencephalographic
      suppression, prone position, altered heart rate variability, conduction
      abnormalities, gender, or antiepileptic medications, to name a few. More
      recently, potential neuroimaging biomarkers have also been identified. Still,
      despite the increased mortality risk in people with epilepsy due to SUDEP, little
      is known about its underlying pathophysiology. The pathogenesis is likely to be
      multifactorial, resulting in neurogenic pulmonary edema or, in some cases, fatal
      cardiac arrhythmias. Medical examiners can provide an important role in our
      understanding of the magnitude of the problem and ongoing research into the
      underlying mechanisms. In this review, we discuss diagnostic criteria, incidence,
      risk factors, and current theories regarding the pathophysiology of SUDEP.

PMID- 29596067
TI  - Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin
      Signaling: Erratum.

PMID- 29596068
TI  - Factors Associated With Canadian Nurses' Informatics Competency.
AB  - As digital innovations continue to transform health systems in Canada, it is
      important to examine registered nurses' preparedness in informatics, and factors
      associated with informatics competency. An exploratory, descriptive, cross
      sectional survey was used to determine self-perceived informatics competencies,
      and factors associated with competency, among practicing nurses in Alberta.
      Results from 2844 completed surveys showed that nurses' self-perceived
      informatics competency was slightly above the mark of competent. Perceptions of
      competency were highest on foundational computer literacy skills and lowest on
      information and knowledge management competencies. However, overall informatics
      competency mean scores varied significantly in relation to age, educational
      qualification, years of experience, and work setting. The quality of informatics
      training and support offered by employers contributed the most to variance in
      mean scores of total and subdomains of informatics competency. Other factors,
      such as age, educational qualification, work setting, previous informatics
      education, access to the Internet, use of health technology, access to supporting
      resources, informatics training, an informatics role, and continuing education in
      informatics, also contributed to mean scores variance in differing degrees.
      Findings from this study provide a basis for actionable policies to address
      informatics educational needs and support requirements among nurses practicing
      now and in the future.

PMID- 29596069
TI  - Validation of the Microlife WatchBP Home blood pressure device in pregnancy for
      medium and large arm circumferences.
AB  - OBJECTIVE: The Microlife WatchBP Home automated blood pressure device was
      assessed for accuracy in pregnant women of medium (<32 cm) and large (>=32 cm)
      arm circumference. MATERIALS AND METHODS: The British Hypertension Society
      validation protocol was modified for the purpose of this study to include women
      with arm circumference of less than 32 cm (N=51) and greater than or equal to 32
      cm (N=46) as two separate arms. RESULTS: The device achieved an overall A/A grade
      for medium arm circumference and B/A grade for large arm circumference. The
      mean+/-SD device-observer difference was 1.7+/-6.2 and -0.4+/-4.4 for systolic
      and diastolic blood pressure, respectively, for medium arm circumference and
      3.0+/-8.5 and 1.5+/-5.1, respectively, for large arm circumference. When all
      women with pre-eclampsia from both groups were pooled (N=23), the device achieved
      an overall grade of A/A with mean differences of 2.1+/-7.2 for systolic blood
      pressure and 1.0+/-5.6 for diastolic blood pressure. CONCLUSION: The Microlife
      WatchBP Home automated blood pressure device can be recommended for use in
      pregnant women of all gestations, including those with pre-eclampsia. However,
      caution is needed for women with large arm circumferences.

PMID- 29596070
TI  - Chronic Myelomonocytic Leukemia With Fibrosis Is a Distinct Disease Subset With
      Myeloproliferative Features and Frequent JAK2 p.V617F Mutations.
AB  - A subset of patients with chronic myelomonocytic leukemia (CMML) presents with
      significance myelofibrosis. In myelodysplastic syndromes, significant
      myelofibrosis has been associated with adverse outcomes and p53 dysregulation.
      However, in CMML the clinical and molecular correlates of significant
      myelofibrosis at presentation remain poorly understood. From a cohort of 651 CMML
      patients, we identified retrospectively 20 (3.1%) cases with moderate to severe
      reticulin fibrosis (CMML-F) detected at diagnosis, and we compared them to CMML
      patients without fibrosis (n=631) seen during the same period. Patients with CMML
      F had a median age of 69.8 years (range, 24.8 to 91.2 y) and most (13; 65%) were
      men. Patients with CMML-F differed significantly from other CMML patients across
      the following parameters: white blood count, absolute monocyte count, serum
      lactate dehydrogenase level, splenomegaly, and bone marrow blast percentage.
      Notably, the frequency of JAK2 p.V617F mutation was higher in CMML-F patients
      compared with other CMML patients (P<0.001). Most CMML-F patients (12/20; 60%)
      had myeloproliferative CMML. Dysregulation of p53 was uncommon in CMML-F. CMML-F
      patients tended to have a shorter median overall survival compared with other
      CMML patients (P=0.079). Multivariate analysis using the Cox proportional hazards
      model showed an independent association between CMML-F and overall survival
      (P=0.047). In summary, unlike typical CMML, CMML-F is commonly associated with
      JAK2 p.V617F. The high frequency of myeloproliferative features and JAK2 p.V617F
      mutation, and the low frequency of p53 dysregulation, suggest that fibrosis in
      the context of CMML has a different pathogenesis from that previously reported in
      myelodysplastic syndrome.

PMID- 29596071
TI  - An Observational Cohort Study Examining the Effect of the Duration of Skin-to
      Skin Contact on the Physiological Parameters of the Neonate in a Neonatal
      Intensive Special Care Unit.
AB  - BACKGROUND: Focus on skin-to-skin contact (SSC) as a family-centered care
      intervention in Neonatal Intensive Special Care (NISC) Units continues to
      increase. Previously, SSC has been shown to improve neonatal physiological
      stability, support brain development, and promote bonding and attachment. Limited
      research exists investigating SSC duration and neonatal physiological responses.
      PURPOSE: This study examined the relationship between SSC duration and the
      neonate's oxygen saturation, heart rate (HR), respiratory rate (RR), and
      temperature. METHOD: An observational cohort study was conducted at The Royal
      Women's Hospital NISC Unit in Melbourne, Australia. For each neonate participant,
      1 SSC with their parent was studied (parent convenience) and neonatal
      physiological parameters recorded, with a bivariate correlation used to explore
      the relationship between the duration of SSC and the percentage of time during
      SSC that the neonate's physiological variables remained within a target range.
      FINDINGS: No correlation existed between the duration of SSC and the neonatal
      physiological variables of oxygen saturation, HR, RR, and temperature. However,
      neonatal oxygen requirement was more often reduced across the duration of SSC.
      IMPLICATIONS FOR PRACTICE AND FUTURE RESEARCH: Due to previously documented
      benefits to neonates physiologically from SSC, and our supportive finding that
      SSC reduces neonatal oxygen requirement, we believe that this study adds to the
      evidence to support promotion of SSC in NISC Units. The duration of SSC does not
      appear to negatively impact the physiological effects to the neonate. Thus, SSC
      should be encouraged in all NISC Units to be conducted for the length of time the
      parent is able. This study should be repeated with a larger sample size.

PMID- 29596072
TI  - The Speaker Gender Gap at Critical Care Conferences.
AB  - OBJECTIVES: To review women's participation as faculty at five critical care
      conferences over 7 years. DESIGN: Retrospective analysis of five scientific
      programs to identify the proportion of females and each speaker's profession
      based on conference conveners, program documents, or internet research. SETTING:
      Three international (European Society of Intensive Care Medicine, International
      Symposium on Intensive Care and Emergency Medicine, Society of Critical Care
      Medicine) and two national (Critical Care Canada Forum, U.K. Intensive Care
      Society State of the Art Meeting) annual critical care conferences held between
      2010 and 2016. SUBJECTS: Female faculty speakers. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Male speakers outnumbered female speakers at all
      five conferences, in all 7 years. Overall, women represented 5-31% of speakers,
      and female physicians represented 5-26% of speakers. Nursing and allied health
      professional faculty represented 0-25% of speakers; in general, more than 50% of
      allied health professionals were women. Over the 7 years, Society of Critical
      Care Medicine had the highest representation of female (27% overall) and
      nursing/allied health professional (16-25%) speakers; notably, male physicians
      substantially outnumbered female physicians in all years (62-70% vs 10-19%,
      respectively). Women's representation on conference program committees ranged
      from 0% to 40%, with Society of Critical Care Medicine having the highest
      representation of women (26-40%). The female proportions of speakers, physician
      speakers, and program committee members increased significantly over time at the
      Society of Critical Care Medicine and U.K. Intensive Care Society State of the
      Art Meeting conferences (p < 0.05), but there was no temporal change at the other
      three conferences. CONCLUSIONS: There is a speaker gender gap at critical care
      conferences, with male faculty outnumbering female faculty. This gap is more
      marked among physician speakers than those speakers representing nursing and
      allied health professionals. Several organizational strategies can address this
      gender gap.

PMID- 29596073
TI  - The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction
      Model.
AB  - OBJECTIVES: To develop an acute kidney injury risk prediction model using
      electronic health record data for longitudinal use in hospitalized patients.
      DESIGN: Observational cohort study. SETTING: Tertiary, urban, academic medical
      center from November 2008 to January 2016. PATIENTS: All adult inpatients without
      pre-existing renal failure at admission, defined as first serum creatinine
      greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th
      Edition, code for chronic kidney disease stage 4 or higher or having received
      renal replacement therapy within 48 hours of first serum creatinine measurement.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, vital signs,
      diagnostics, and interventions were used in a Gradient Boosting Machine algorithm
      to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage
      2 acute kidney injury, with 60% of the data used for derivation and 40% for
      validation. Area under the receiver operator characteristic curve (AUC) was
      calculated in the validation cohort, and subgroup analyses were conducted across
      admission serum creatinine, acute kidney injury severity, and hospital location.
      Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease
      Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage
      2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney
      injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96
      (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48
      hours. Accuracy was similar across hospital settings (ICU, wards, and emergency
      department) and admitting serum creatinine groupings. At a probability threshold
      of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a
      specificity of 85% for stage 2 acute kidney injury and predicted the development
      of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the
      development of stage 2 acute kidney injury. CONCLUSIONS: Readily available
      electronic health record data can be used to predict impending acute kidney
      injury prior to changes in serum creatinine with excellent accuracy across
      different patient locations and admission serum creatinine. Real-time use of this
      model would allow early interventions for those at high risk of acute kidney
      injury.

PMID- 29596074
TI  - Psychological Impact of Pregnancy Loss: Best Practice for Obstetric Providers.
AB  - Three overlapping areas of study form the foundation of the psychological impact
      of pregnancy loss: (1) transition to parenthood and the development of
      attachment, (2) perinatal mental health disorders, and (3) complicated grief.
      This article integrates findings from prominent lineages of theory to offer the
      obstetric provider an evidence-based framework for patient care. Current
      consensus across fields of study is that preexisting depression and anxiety are
      the strongest predictors of psychological functioning after loss and through the
      subsequent pregnancy. Compassionate care, informational guidance and timed follow
      up positively impact patient outcomes. The article concludes with recommendations
      for obstetric provider training and self-care.

PMID- 29596075
TI  - Managing Heavy Menstrual Bleeding in Women at Risk of Thrombosis.
AB  - Management of heavy menstrual bleeding (HMB) in a woman with a history of
      thrombosis, or who is otherwise at high risk of thrombosis, or who takes
      medications for anticoagulation can present a challenge to health care providers.
      The goal of treating HMB is to reduce menstrual blood loss. First-line therapy is
      typically hormonal, and hormonal therapy can be contraindicated in women with a
      history of thrombosis unless they are on anticoagulation. As 70% of women on
      anticoagulation experience HMB, successful management of HMB may involve a
      modification in the anticoagulation or antiplatelet regimen, hormonal therapy
      tailored to the patient's situation, and/or surgical therapy.

PMID- 29596077
TI  - Anterior Cruciate Ligament Injuries in the National Hockey League: Epidemiology
      and Performance Impact.
AB  - OBJECTIVE: To determine the incidence of anterior cruciate ligament (ACL)
      injuries in the National Hockey League (NHL) and to examine the effects of this
      injury on return-to-play status and performance. DESIGN: Case series; level of
      evidence, 4. METHODS: This was a 2-phase study. Phase I used the NHL electronic
      injury surveillance system and Athlete Health Management System to collect data
      on ACL injuries and man games lost over 10 seasons (2006/2007-2015/2016). Data
      collected in phase I were received in deidentified form. Phase II examined the
      performance impact of an ACL injury. Players were identified through publically
      available sources, and performance-related statistics were analyzed. Data
      collected in phase II were not linked to data collected in phase I. A paired t
      test was used to determine any difference in the matching variables between
      controls and cases in the preinjury time period. A General linear model (mixed)
      was used to determine the performance impact. RESULTS: Phase I: 67 ACL injuries
      occurred over 10 seasons. The incidence for all players was 0.42/1000 player game
      hours (forward, 0.61; defenseman, 0.32, goalie, 0.08) and by game exposure was
      0.2/1000 player game exposures (forward, 0.33; defenseman, 0.11; goalie, 0.07).
      Forwards had a greater incidence rate of ACL tears with both game hours and game
      exposures when compared with defensemen and goalies (P < 0.001, <0.001; P =
      0.008, <0.001, respectively). Phase II: 70 ACL tears (60 players) were
      identified. Compared with controls, players who suffered an ACL tear demonstrated
      a decrease in goals/season (P < 0.04), goals/game (P < 0.015), points/season
      (0.007), and points/game (0.001). Number of games and seasons played after an ACL
      injury did not differ compared with controls (P = 0.068, 0.122, respectively).
      CONCLUSIONS: Anterior cruciate ligament injuries occur infrequently, as it
      relates to other hockey injuries. Despite a high return to play, the performance
      after an ACL injury demonstrated a decrease in points and goals per game and per
      season.

PMID- 29596076
TI  - Predictors of Postpartum Depression: A Comprehensive Review of the Last Decade of
      Evidence.
AB  - Postpartum depression (PPD) is one of the most frequent complications of
      childbirth affecting ~500,000 women annually (prevalence 10% to 15%). Despite the
      documented adverse outcomes for mother and child, there remains a great need to
      develop prospective approaches to identify women at risk. This review examines
      some of the best-characterized molecular and clinical risk factors for PPD. We
      illustrate that this is a growing literature but there remains a lack of reliable
      molecular predictors for PPD. Current best predictors are clinical assessments
      for psychiatric history and adverse life events, highlighting the need for
      increased depression screening across the perinatal period.

PMID- 29596079
TI  - Abductor Tendon Tears of the Hip.

PMID- 29596078
TI  - Reduction in postpercutaneous coronary intervention angina in addition to
      gastrointestinal events in patients on combined proton pump inhibitors and dual
      antiplatelet therapy: a systematic review and meta-analysis.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) is a standard
      treatment in patients with acute coronary syndrome. Studies have shown that
      proton pump inhibitors (PPIs) can potentially attenuate the antiplatelet effects
      of P2Y12 inhibitors with associated adverse cardiovascular outcomes. MATERIALS
      AND METHODS: Medline was searched using Pubmed from inception to 8 November 2017
      for randomized control trials studying the effect of PPIs on coronary artery
      disease with concomitant use of dual antiplatelet therapy (DAPT). Overall, 692
      studies were identified of which five randomized control trials were included.
      Statistical analysis was done using RevMan, version 5.3. RESULTS: Five studies
      with 6239 patients (3113 on PPI with DAPT and 3126 with only DAPT) were included.
      Our analysis showed that PPI significantly reduced the incidence of
      gastrointestinal (GI) bleed [22 vs. 66, odds ratio (OR)=0.37, confidence interval
      (CI)=0.23-0.61, P<=0.0001, I=0%], GI ulcers and GI erosions (7 vs. 18, OR=0.39,
      CI=0.16-0.94, P=0.04, I=0%), and the incidence of post-PCI unstable angina in
      patients treated with PPI and P2Y12 agents (46 vs. 67, OR=0.67, CI=0.45-0.99,
      P=0.05, I=0%). There was an insignificant difference in myocardial infarction,
      stroke, and cardiovascular cause of mortality. A trend toward decreased all-cause
      mortality with PPIs was noted. Heterogeneity was calculated using I. CONCLUSION:
      Concomitantly administered PPIs with P2Y12 inhibitors have a protective effect on
      the GI events. It also decreases the post-PCI angina without increased adverse
      cardiovascular outcomes.

PMID- 29596080
TI  - Low-Dose Characterization of Kidney Stones Using Spectral Detector Computed
      Tomography: An Ex Vivo Study.
AB  - OBJECTIVES: The aim of this study was to investigate the feasibility of kidney
      stone composition analysis using spectral detector computed tomography scanner
      (SDCT) with normal- and low-dose imaging protocols. METHODS: A total of 154
      stones harvested from nephrolithotripsy or nephrolithotomy with a known
      monocrystalline composition as determined by infrared spectroscopy were examined
      in a nonanthropomorphic phantom on an SDCT (IQon, Philips, Best, the
      Netherlands). Imaging was performed with 120 kVp and (a) 40 mAs and (b) 200 mAs,
      resulting in a computed tomography dose index (CTDIvol) of 2 and 10 mGy,
      respectively. Besides conventional CT images (CIs), SDCT enables reconstruction
      of virtual monoenergetic images (40-200 keV). Spectral coefficient images were
      calculated by performing a voxel-by-voxel combination of 40 and 200 keV images
      (Matlab R2017b, Mathworks Inc). All stones were semiautomatically 3D-segmented on
      CI using a threshold-based algorithm implemented in an offline DICOM viewer.
      Statistical assessment was performed using Steel-Dwass method to adjust for
      multiple comparisons. RESULTS: Ca-phosphate (n = 22), Ca-oxalate (n = 82),
      cysteine (n = 20), struvite (n = 3), uric acid (n = 18), and xanthine stones (n =
      9) were included in the analysis. Stone diameter ranged from 3.0 to 13.5 mm. On
      CI, attenuation differed significantly between calcific and noncalcific stones
      only (P <= 0.05), the spectral coefficient differed significantly between (//):
      Ca-oxalate//Ca-phosphate//cystine//struvite//uric acid//xanthine in 10 mGy
      protocol (all P <= 0.05). The same results were found for the 2 mGy-protocol,
      except that differentiation of Ca-oxalate and Ca-phosphate as well as uric acid
      and xanthine was not possible (P >= 0.05). CONCLUSIONS: Spectral detector CT
      allows for differentiation of kidney stones using semi-automatic segmentation and
      advanced image post-processing, even in low-dose imaging protocols.

PMID- 29596081
TI  - Relationships Between the ACGME Resident and Faculty Surveys and Program Pass
      Rates on the ABIM Internal Medicine Certification Examination.
AB  - PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) has
      surveyed residents since 2003, and faculty since 2012. Surveys are designed to
      assess program functioning and specify areas for improvement. The purpose of this
      study was to assess the association of the ACGME's resident and faculty surveys
      with residency-program-specific performance on the American Board of Internal
      Medicine (ABIM) certification exam. METHOD: Data were available from residents
      and faculty in 375 U.S. ACGME-accredited internal medicine programs from the 2012
      2013, 2013-2014, and 2014-2015 academic years. Analysis of variance and
      correlations were used to examine the relationship between noncompliance with
      ACGME program requirements as assessed by the resident and faculty surveys, and
      ABIM program pass rates. RESULTS: Noncompliance reported on the resident and
      faculty surveys was highest for programs not meeting the ACGME program
      requirement of an 80% pass rate on the ABIM certification examination. This
      relationship was significant for overall noncompliance, both within the resident
      (P < .001) and faculty (P < .05) surveys, for many areas within the two surveys
      (correlations ranged between -.07 and -.25, and P values ranged between .20 and <
      .001), and for the highest levels of noncompliance across areas of the resident
      (P < .001) and faculty (P < .04) surveys. CONCLUSIONS: ACGME resident and faculty
      surveys were significantly associated with ABIM program pass rates, supporting
      the importance of these surveys within the ACGME's Next Accreditation System.

PMID- 29596082
TI  - Transformative Learning and Professional Identity Formation During International
      Health Electives: A Qualitative Study Using Grounded Theory.
AB  - PURPOSE: International health electives (IHEs) are widely available during
      residency and provide unique experiences for trainees. Theoretical models of
      professional identity formation and transformative learning may provide insight
      into residents' experiences during IHEs. The purpose of this study was to explore
      transformative learning and professional identity formation during resident IHEs
      and characterize the relationship between transformative learning and
      professional identity formation. METHOD: The authors used a constructivist
      grounded theory approach, with the sensitizing concepts of transformative
      learning and professional identity formation to analyze narrative reflective
      reports of residents' IHEs. The Mayo International Health Program supports
      residents from all specialties across three Mayo Clinic sites. In 2015, the
      authors collected narrative reflective reports from 377 IHE participants dating
      from 2001 to 2014. Reflections were coded and themes were organized into a model
      for transformative learning during IHEs, focusing on professional identity.
      RESULTS: Five components of transformative learning were identified during IHEs:
      a disorienting experience; an emotional response; critical reflection;
      perspective change; and a commitment to future action. Within the component of
      critical reflection, three domains relating to professional identity were
      identified: making a difference; the doctor-patient relationship; and medicine in
      its "purest form." Transformation was demonstrated through perspective change and
      a commitment to future action, including continued service, education, and
      development. CONCLUSIONS: IHEs provide rich experiences for transformative
      learning and professional identity formation. Understanding the components of
      transformative learning may provide insight into the interaction between learner,
      experiences, and the influence of mentors in the process of professional identity
      formation.

PMID- 29596083
TI  - The Scope of Extraprofessional Caregiving Challenges Among Early Career Faculty:
      Findings From a University Medical Center.
AB  - PURPOSE: Academic scientists work in competitive environments, and many
      institutions invest in career development supports. These investments may be
      imperiled when extraprofessional demands challenge a faculty member's reserve
      capacity. This research assessed prevalence of caregiving challenges and
      estimated incidence of stressful life events. METHOD: In 2015-2016, the authors
      surveyed recipients of career development awards supporting >= 75% effort and
      individuals within the funding period of their first National Institutes of
      Health R01 or equivalent at Vanderbilt University Medical Center. Domains
      included family structure, hospitalizations of family members, responsibility for
      coordination of caregiving, and an inventory of stressful life events. RESULTS:
      Seventy-two percent (152 of 210) of early career researchers responded. Over half
      endorsed experiencing one or more substantial caregiving challenges in the prior
      year. This included 35 (23%) having a child or adult in the household
      hospitalized in the prior year and 36 (24%) being responsible for health care
      needs for a child or adult in the household, or for coordinating elder care,
      assisted living, or hospice care. The majority experienced one or more caregiving
      challenges. Stressful life events increased relative risk of "thinking about
      leaving academics" by 70% (risk ratio: 1.7; 95% confidence interval: 1.2, 2.4).
      Prevalence and incidence of caregiving demands did not differ by gender.
      CONCLUSIONS: Leaders, administrators, mentors, and faculty should anticipate that
      most women and men early career researchers will experience substantial
      caregiving challenges and life events in any given year. Sufficient need exists
      to warrant investigation of institutional programs to address caregiving
      challenges.

PMID- 29596084
TI  - Combined Surgery and Intraoperative Sclerotherapy for Vascular Malformations of
      the Head/Neck: The Hybrid Approach.
AB  - Vascular malformations (VMs) of the head and neck can lead to aesthetic problems
      as well as cranial nerve damage, airway compromise, and vision loss. Large VMs
      are typically managed surgically, with sclerotherapy or embolization performed in
      the perioperative period to decrease the risk of excessive blood loss and
      minimize the size of the VM. However, this initial treatment is frequently
      insufficient leading to excessive blood loss intraoperatively, poorer margin
      visualization for the surgeon, and decreased likelihood of complete resection. As
      a result, resections of large VMs are often performed in a multistage approach.
      This article introduces a new hybrid approach for the management of head and neck
      VMs entailing the use of an endovascular operating room where a neuroendovascular
      surgeon performs embolization or sclerotherapy intraoperatively as needed in
      conjunction with surgical excision. Three patients with large VMs in the facial
      region underwent successful use of the hybrid approach. The hybrid approach
      improved visualization, leading to complete resection in 1 patient and nearly
      complete resections (70% and 90%) in the other patients. The technique also
      helped minimize blood loss because only the youngest patient (23 months old)
      required a blood transfusion. Implications of these findings include the
      transition from a multistaged approach for large VMs to a single-stage approach.
      In addition, decreases in blood loss may allow for the development and use of
      minimal access techniques, leading to a decrease in visible scarring for
      patients. We suggest the consideration of the hybrid approach for large head and
      neck VMs.

PMID- 29596085
TI  - The Influence of Connective Tissue Disease in Breast Reconstruction: A National
      Database Analysis.
AB  - BACKGROUND: Patients with connective tissue diseases (CTD), or collagen vascular
      diseases, are at risk of potentially higher morbidity after surgical procedures.
      We aimed to investigate the complication profile in CTD versus non-CTD patients
      who underwent breast reconstruction on a national scale. METHODS: A retrospective
      analysis of the Healthcare Cost and Utilization Project NIS Database between 2010
      and 2014 was conducted for patients 18 years or older admitted for immediate
      autologous or implant breast reconstruction. Connective tissue disease was
      defined as systemic lupus erythematosus, rheumatoid arthritis, systemic
      sclerosis, scleroderma, Raynaud phenomenon, psoriatic arthritis, or sarcoidosis.
      Independent t test/Wilcoxon-Mann-Whitney was used to compare continuous variables
      and Pearson chi/Fischer exact test was used for categorical variables. Outcomes
      of interest were assessed using multivariable linear regressions for continuous
      variables and multivariable logistic regressions for categorical variables.
      RESULTS: There were 19,496 immediate autologous breast reconstruction patients,
      with 357 CTD and 19,139 non-CTD patients (2010-2014). The CTD patients had higher
      postoperative complication rates for infection (2.8% vs 0.8%, P < 0.001), wound
      dehiscence (1.4% vs 0.4%, P = 0.019), and bleeding (hemorrhage and hematoma)
      (6.7% vs 3.5%, P < 0.001). After multivariable analysis, CTD remained an
      independent risk factor for bleeding (odds ratio [OR], 1.568; 95% confidence
      interval [CI], 1.019-2.412). There were a total of 23,048 immediate implant
      breast reconstruction patients, with 431 CTD and 22,617 non-CTD patients (2010
      2014). The CTD patients had a higher postoperative complication rate for wound
      dehiscence/complication (2.3% vs 0.6%, P < 0.001). They also experienced a longer
      length of stay (2.31 days vs 2.07 days, P < 0.001). After multivariable analysis,
      CTD remained an independent risk factor for wound dehiscence (OR, 4.084; 95% CI,
      2.101-7.939) and increased length of stay by 0.050 days (95% CI, -0.081 to
      0.181). CONCLUSIONS: Connective tissue disease patients who underwent autologous
      breast reconstruction had significantly higher infection, wound dehiscence, and
      bleeding rates, and those who underwent implant breast reconstruction had
      significantly higher wound dehiscence rates. Connective tissue diseases appear to
      be an independent risk factor for bleeding and wound dehiscence in autologous and
      implant breast reconstruction, respectively. This information may help clinicians
      be aware of this increased risk when determining patients for reconstruction.

PMID- 29596086
TI  - Work/Life Balance: It Is Just Plain Hard.
AB  - Graduating surgeons are constantly told to be "available, affable, and able."
      Frequently, the need to put patients first can result in an imbalance between
      work and life. Ultimately, the consequence of work/life imbalance is burnout,
      which can manifest itself in atypical behavior toward patients, colleagues, and
      family. It is imperative that all surgeons learn to take care of themselves and
      develop a better integration of work and life.

PMID- 29596087
TI  - Analysis of Follicle-Stimulating Hormone Receptor in Infantile Hemangioma.
AB  - INTRODUCTION: The life cycle of infantile hemangioma (IH) and secretion of
      follicle-stimulating hormone (FSH) are identical. We previously have shown that
      IH contains the FSH receptor (FSHR). The purpose of this study was to identify
      which cell type(s) in IH expresses FSHR. METHODS: Human proliferating IH tissues
      obtained during a clinically indicated surgical procedure were used. Paraffin
      sections and isolated cell populations (endothelial, pericyte, stem cell) were
      subjected to immunofluorescence for FSHR. Tissues were costained with DAPI, anti
      alpha smooth muscle actin, or biotinylated Ulex Europaeus Agglutinin I to
      identify nuclei, pericytes, and endothelial cells, respectively. Whole tissue and
      purified single cell populations underwent polymerase chain reaction (PCR) for
      FSHR. Positive control specimens (ovary, sertoli cells) and negative control
      tissues (skin/subcutis, hepatic cells) were included. RESULTS: Immunofluorescence
      of 9 IHs demonstrated that FSHR was enriched in pericytes compared with
      endothelial cells. Follicle-stimulating hormone receptor was expressed in 6 of 6
      whole tissue IHs along with the positive control via PCR. Follicle-stimulating
      hormone receptor was not present in the negative control samples. Four of 5 sets
      of pericytes expressed FSHR by PCR. Neither IH endothelial cells, IH stem cells,
      nor negative control cells exhibited FSHR by PCR. CONCLUSIONS: Because the
      secretion of FSH correlates with the growth pattern of IH, FSH might be involved
      in the disease process. Follicle-stimulating hormone receptor is enriched in the
      pericytes of IH, suggesting that this cell type may be involved in the
      pathogenesis of the tumor.

PMID- 29596088
TI  - A Systematic Review of Prognostic Factors for Sensory Recovery After Digital
      Nerve Reconstruction.
AB  - BACKGROUND: Successful digital nerve repair is crucial in preventing painful
      neuroma formation and restoring sensory function after traumatic hand injury. The
      purpose of this study is to identify prognostic factors affecting sensory
      recovery following digital nerve reconstruction. METHODS: A systematic review was
      conducted according to Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines including studies reporting patients 18 years and older,
      greater than 10 reconstructed digital nerves, and greater than or equal to 3
      months follow-up. Studies with proximal nerve injuries in the same distribution
      or inadequate sensory data were excluded. Included studies were evaluated by
      methodological index for nonrandomized studies score. Possible predictors were
      examined using the t test and 1-way analysis of variance with alpha <= 0.05.
      RESULTS: Twenty-five studies met the inclusion criteria, consisting of 818
      surgically reconstructed digital nerves (mean age, 38 years; 78% male) with a
      mean +/- SD defect length of 1.5 +/- 0.5 cm. Mean follow-up time was 22 months.
      Fifty-six percent of patients presented with concomitant injuries to tendons
      (31%) and the digital artery (13%). Mean +/- SD time to surgical repair was 36 +/
      73.8 days. Reconstructive techniques included 35% end-to-end primary
      neurorrhaphy, 31% nerve grafts, and 11% synthetic conduits. Postoperatively, 81%
      of the patients demonstrated sensory recovery of S3+/S4, with 45% complaining of
      hyperesthesia. Nerve reconstructions performed within 15 days of injury had
      significantly better static 2-point discrimination than delayed procedures (P =
      0.02). Static 2-point discrimination measurements were also significantly better
      for shorter defect lengths (<1.3 cm, P = 0.05). No significant functional
      differences were found across age, follow-up time, injured digit or side, nor
      reconstructive technique. CONCLUSIONS: Digital nerve reconstruction has good to
      excellent sensory recovery in up to 81% of patients with improved results in
      nerve gaps less than 1.3 cm. Performing the reconstruction within 15 days of
      injury is also correlated with improved sensory recovery.

PMID- 29596089
TI  - The Unexpected Life: Living With Hand Transplant.

PMID- 29596090
TI  - Using Mesh to Reinforce the Abdominal Wall in Abdominal Free Flaps for Breast
      Reconstruction: Is There a Benefit? What are the Risks?
AB  - INTRODUCTION: Abdominal wall integrity may be compromised after abdominal flap
      harvest for breast reconstruction, leading to bulging or herniation due to
      weakening of the abdominal wall and dissection through the rectus muscle. Mesh
      can be used to reinforce the abdominal wall to reduce the risk of hernia
      formation postoperatively, especially in patients who may be at high risk. In
      this study, we describe this institution's experience with the use of mesh in the
      abdominal wall and critically evaluate its impact on patient outcomes and
      complications. METHODS: We retrospectively reviewed all patients with an
      abdominal free flap harvested for breast reconstruction at Stanford Health Care
      from 2005 to 2015. Multivariate-adjusted logistic regression analysis was used to
      compare the odds of abdominal complications-infection, bulging, and herniation
      between patients with and without an abdominal mesh implanted during breast
      reconstruction. RESULTS: Three hundred eighty patients met inclusion criteria.
      One hundred sixty-one patients received mesh, whereas 219 received no
      reinforcement. In the mesh group, there were 7 (4.3%) cases of postoperative
      abdominal bulging, 11 (6.8%) cases of abdominal infection, and no (0.0%) cases of
      herniation. In the group without mesh, there were 17 (7.8%) cases of abdominal
      bulging, 11 (5.0%) cases of abdominal infection, and 5 (2.3%) cases of
      herniation. There was a significant difference in the odds of bulging (odds ratio
      [OR], 0.30; P = 0.01). There was not a significant difference in the odds of
      herniation (OR, 2.26E-10; P = 0.99) or infection (OR, 1.21; P = 0.69).
      CONCLUSIONS: In our current treatment algorithm, patients who received mesh were
      selected based upon several criteria, including obesity, weak fascia identified
      during surgery, and extensive muscle dissection. We confirm that the risk of
      bulging and herniation is decreased in patients receiving mesh. Furthermore, the
      risk of wound infection was not associated with the use of mesh; instead, a
      patient's elevated body mass index, as well as tension of closure, and other
      comorbidities are more likely causes of superficial wound complications. We find
      the use of mesh to be safe and beneficial in select patients undergoing abdominal
      free flap breast reconstruction who are at risk for hernias and bulges.

PMID- 29596091
TI  - Flupirtine, an Effective Analgesic, but Hepatotoxicity Should Limit Its Use.

PMID- 29596092
TI  - The Impact of Postreperfusion Syndrome on Acute Kidney Injury in Living Donor
      Liver Transplantation: A Propensity Score Analysis.
AB  - BACKGROUND: Postreperfusion syndrome (PRS) has been shown to be related to
      postoperative morbidity and graft failure in orthotopic liver transplantation. To
      date, little is known about the impact of PRS on the prevalence of postoperative
      acute kidney injury (AKI) and the postoperative outcomes after living donor liver
      transplantation (LDLT). The purpose of our study was to determine the impact of
      PRS on AKI and postoperative outcomes after LDLT surgery. METHODS: Between
      January 2008 and October 2015, we retrospectively collected and evaluated the
      records of 1865 patients who underwent LDLT surgery. We divided the patients into
      2 groups according to the development of PRS: PRS group (n = 715) versus no PRS
      group (n = 1150). Risk factors for AKI and mortality were investigated by
      multivariable logistic and Cox proportional hazards regression model analysis.
      Propensity score (PS) analysis (PS matching and inverse probability of treatment
      weighting analysis) was designed to compare the outcomes between the 2 groups.
      RESULTS: The prevalence of PRS and the mortality rate were 38% and 7%,
      respectively. In unadjusted analyses, the PRS group showed more frequent
      development of AKI (P < .001), longer hospital stay (P = .010), and higher
      incidence of intensive care unit stay over 7 days (P < .001) than the no PRS
      group. After PS matching and inverse probability of treatment weighting analysis,
      the PRS group showed a higher prevalence of postoperative AKI (P = .023 and P =
      .017, respectively) and renal dysfunction 3 months after LDLT (P = .036 and P =
      .006, respectively), and a higher incidence of intensive care unit stay over 7
      days (P = .014 and P = .032, respectively). CONCLUSIONS: We demonstrated that the
      magnitude and duration of hypotension caused by PRS is a factor contributing to
      the development of AKI and residual renal dysfunction 3 months after LDLT.

PMID- 29596093
TI  - Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With
      Traumatic Brain Injury.
AB  - BACKGROUND: Exposure to anesthetics is common in the majority of early survivors
      of life-threatening injuries. Whether and to what degree general anesthetics
      influence outcomes from major trauma is unknown. Potential confounding effects of
      general anesthetics on outcome measures are usually disregarded. We hypothesized
      that exposure to isoflurane or sevoflurane modulates the outcome from blunt
      trauma with traumatic brain injury (bTBI). METHODS: We tested the hypothesis in a
      novel model of bTBI implemented in Drosophila melanogaster. Fruit flies of the
      standard laboratory strain w were cultured under standard conditions. We titrated
      the severity of bTBI to a mortality index at 24 hours (MI24) of approximately 20%
      under control conditions. We administered standard doses of isoflurane and
      sevoflurane before, before and during, or after bTBI and measured the resulting
      MI24. We report the MI24 as mean +/- standard deviation. RESULTS: Isoflurane or
      sevoflurane administered for 2 hours before bTBI reduced the MI24 from 22.3 +/-
      2.6 to 10.4 +/- 1.8 (P < 10, n = 12) and from 19.3 +/- 0.9 to 8.9 +/- 1.1 (P <
      .0001, n = 8), respectively. In contrast, administration of isoflurane after bTBI
      increased the MI24 from 18.5% +/- 4.3% to 25.3% +/- 9.1% (P = .0026, n = 22),
      while sevoflurane had no effect (22.4 +/- 7.1 and 21.5 +/- 5.8, n = 22).
      CONCLUSIONS: In a whole animal model of bTBI, general anesthetics were not
      indifferent with respect to early mortality. Therefore, collateral effects of
      general anesthetics should be considered in the interpretation of results
      obtained in vertebrate trauma models. Invertebrate model organisms can serve as a
      productive platform to interrogate anesthetic targets that mediate collateral
      effects and to inform trauma research in higher organisms about the potential
      impact of anesthetics on outcomes.

PMID- 29596094
TI  - Database Quality and Access Issues Relevant to Research Using Anesthesia
      Information Management System Data.
AB  - For this special article, we reviewed the computer code, used to extract the
      data, and the text of all 47 studies published between January 2006 and August
      2017 using anesthesia information management system (AIMS) data from Thomas
      Jefferson University Hospital (TJUH). Data from this institution were used in the
      largest number (P = .0007) of papers describing the use of AIMS published in this
      time frame. The AIMS was replaced in April 2017, making this finite sample
      finite. The objective of the current article was to identify factors that made
      TJUH successful in publishing anesthesia informatics studies. We examined the
      structured query language used for each study to examine the extent to which
      databases outside of the AIMS were used. We examined data quality from the
      perspectives of completeness, correctness, concordance, plausibility, and
      currency. Our results were that most could not have been completed without
      external database sources (36/47, 76.6%; P = .0003 compared with 50%). The
      operating room management system was linked to the AIMS and was used
      significantly more frequently (26/36, 72%) than other external sources. Access to
      these external data sources was provided, allowing exploration of data quality.
      The TJUH AIMS used high-resolution timestamps (to the nearest 3 milliseconds) and
      created audit tables to track changes to clinical documentation. Automatic data
      were recorded at 1-minute intervals and were not editable; data cleaning occurred
      during analysis. Few paired events with an expected order were out of sequence.
      Although most data elements were of high quality, there were notable exceptions,
      such as frequent missing values for estimated blood loss, height, and weight.
      Some values were duplicated with different units, and others were stored in
      varying locations. Our conclusions are that linking the TJUH AIMS to the
      operating room management system was a critical step in enabling publication of
      multiple studies using AIMS data. Access to this and other external databases by
      analysts with a high degree of anesthesia domain knowledge was necessary to be
      able to assess the quality of the AIMS data and ensure that the data pulled for
      studies were appropriate. For anesthesia departments seeking to increase their
      academic productivity using their AIMS as a data source, our experiences may
      provide helpful guidance.

PMID- 29596095
TI  - Dexamethasone as an Adjuvant for Caudal Blockade in Pediatric Surgical Patients:
      A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Caudal block is commonly used to provide postoperative analgesia
      after pediatric surgery in the lower abdomen. Typically administered as a single
      shot technique, 1 limitation of this block is the short duration of analgesia. To
      overcome this, dexamethasone has been used as an adjuvant to prolong block
      duration. However, there are concerns about steroid-related morbidity and the
      optimal route of dexamethasone administration (eg, caudal or intravenous) is
      unknown. METHODS: We conducted a systematic review and random-effects meta
      analysis of randomized controlled trials recruiting pediatric surgical patients
      receiving a caudal block for surgical anesthesia or postoperative analgesia.
      Included studies compared dexamethasone (caudal, intravenous, or both) to
      control. Duration of analgesia was the primary outcome. Database sources were
      Medline, Embase, the Cochrane Library, and Google Scholar searched up to August
      18, 2017, without language restriction. Screening of studies, data extraction,
      and risk of bias assessment were performed independently and in duplicate by 2
      authors. Risk of bias was assessed using Cochrane methodology and the strength of
      evidence was scored using the Grading of Recommendations Assessment, Development,
      and Evaluation (GRADE) system. RESULTS: The initial search retrieved 93 articles.
      Fourteen randomized controlled trials that comprised 1315 pediatric patients met
      the inclusion criteria. All but 1 study involved lower abdominal operations
      (orchidopexy, inguinal hernia repair, and hypospadias repair). The caudal and
      intravenous dose of dexamethasone ranged from 0.1 to 0.2 mg/kg and 0.5 to 1.5
      mg/kg, respectively, and all studies were pooled in the main analysis.
      Dexamethasone prolonged the duration of analgesia by both the caudal route (5.43
      hours, 95% confidence interval [CI], 3.52-7.35; P < .001; I = 99.3%; N = 9; n =
      620; GRADE quality = moderate) and intravenous route (5.51 hours; 95% CI, 3.56
      7.46; P < .001; I = 98.9%; N = 5; n = 364; GRADE quality = moderate) versus
      control. Secondary benefits of dexamethasone included reduced narcotic rescue
      analgesia requirement in the postanesthetic care unit (relative risk [RR], 0.30;
      95% CI, 0.18-0.51; P < .001; I = 0.0%; N = 5; number needed to treat for benefit
      [NNTB] = 5; 95% CI, 4-7), less subsequent postoperative rescue analgesia
      requirement (RR, 0.46; 95% CI, 0.23-0.92; P = .03; I = 96.0%; N = 9; n = 629;
      NNTB = 3; 95% CI, 2-20; n = 310), and lower rates of postoperative nausea and
      vomiting (RR, 0.47; 95% CI, 0.30-0.73; P = .001; I = 0.0%; NNTB = 11; 95% CI, 8
      21; N = 9; n = 628). Adverse events linked to the dexamethasone were rare.
      CONCLUSIONS: Caudal and intravenous dexamethasone are similarly effective for
      prolonging the duration of analgesia from caudal blockade, resulting in a doubled
      to tripled duration. Given the off-label status of caudal dexamethasone,
      intravenous administration is recommended-although only high intravenous doses
      (0.5 mg/kg up to 10 mg) have been studied.

PMID- 29596096
TI  - Time for a Fresh Approach to Examining Factors Associated With Red Blood Cell
      Transfusion Outcome.

PMID- 29596097
TI  - Repeated Morphine Prolongs Postoperative Pain in Male Rats.
AB  - BACKGROUND: Opioids are effective postoperative analgesics. Disturbingly, we have
      previously reported that opioids such as morphine can worsen inflammatory pain
      and peripheral and central neuropathic pain. These deleterious effects are
      mediated by immune mediators that promote neuronal hyperexcitability in the
      spinal dorsal horn. Herein, we tested whether perioperative morphine could
      similarly prolong postoperative pain in male rats. METHODS: Rats were treated
      with morphine for 7 days, beginning immediately after laparotomy, while the
      morphine was tapered in a second group. Expression of genes for inflammatory
      mediators was quantified in the spinal dorsal horn. In the final experiment,
      morphine was administered before laparotomy for 7 days. RESULTS: We found that
      morphine treatment after laparotomy extended postoperative pain by more than 3
      weeks (time * treatment: P < .001; time: P < .001; treatment: P < .05). Extension
      of postoperative pain was not related to morphine withdrawal, as it was not
      prevented by dose tapering (time * treatment: P = .8; time: P < .001; treatment:
      P = .9). Prolonged postsurgical pain was associated with increased expression of
      inflammatory genes, including those encoding Toll-like receptor 4, NOD like
      receptor protein 3 (NLRP3), nuclear factor kappa B (NFkappaB), caspase-1,
      interleukin-1beta, and tumor necrosis factor (P < .05). Finally, we showed that
      of preoperative morphine, concluding immediately before laparotomy, similarly
      prolonged postoperative pain (time * treatment: P < .001; time: P < .001;
      treatment: P < .001). There is a critical window for morphine potentiation of
      pain, as a 7-day course of morphine that concluded 1 week before laparotomy did
      not prolong postsurgical pain. CONCLUSIONS: These studies indicate the morphine
      can have a deleterious effect on postoperative pain. These studies further
      suggest that longitudinal studies could be performed to test whether opioids
      similarly prolong postoperative pain in the clinic.

PMID- 29596098
TI  - A Dedicated Acute Pain Service Is Associated With Reduced Postoperative Opioid
      Requirements in Patients Undergoing Cytoreductive Surgery With Hyperthermic
      Intraperitoneal Chemotherapy.
AB  - BACKGROUND: The Acute Pain Service (APS) was initially introduced to optimize
      multimodal postoperative pain control. The aim of this study was to evaluate the
      association between the implementation of an APS and postoperative pain
      management and outcomes for patients undergoing cytoreductive surgery with
      hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: In this
      propensity-matched retrospective cohort study, we performed a before-after study
      without a concurrent control group. Outcomes were compared among patients
      undergoing CRS-HIPEC when APS was implemented versus historical controls (non
      APS). The primary objective was to determine if there was a decrease in median
      total opioid consumption during postoperative days 0-3 among patients managed by
      the APS. Secondary outcomes included opioid consumption on each postoperative day
      (0-6), time to ambulation, time to solid intake, and hospital length of stay.
      RESULTS: After exclusion, there were a total of 122 patients, of which 51 and 71
      were in the APS and non-APS cohort, respectively. Between propensity-matched
      groups, the median (quartiles) total opioid consumption during postoperative days
      0-3 was 27.5 mg intravenous morphine equivalents (MEQs) (7.6-106.3 mg MEQs)
      versus 144.0 mg MEQs (68.9-238.3 mg MEQs), respectively. The median difference
      was 80.8 mg MEQs (95% confidence interval, 46.1-124.0; P < .0001). There were
      statistically significant decreases in time to ambulation and time to solid diet
      intake in the APS cohort. CONCLUSIONS: After implementing the APS, CRS-HIPEC
      patients had decreased opioid consumption by >50%, as well as shorter time to
      ambulation and time to solid intake. Implementation of an APS may improve
      outcomes in CRS-HIPEC patients.

PMID- 29596099
TI  - Evidence Basis for Regional Anesthesia in Ambulatory Anterior Cruciate Ligament
      Reconstruction: Part I-Femoral Nerve Block.
AB  - The optimal management of pain after ambulatory anterior cruciate ligament
      reconstruction (ACLR) is unclear. Femoral nerve block (FNB) is purported to
      enhance postoperative analgesia, but its effectiveness in the setting of modern
      multimodal analgesia is unclear. This systematic review examines the effect of
      adding FNB to multimodal analgesia on analgesic outcomes after ACLR, whether or
      not the analgesic regimen used included local instillation analgesia (LIA). We
      retrieved randomized controlled trials evaluating the effects of adding FNB to
      multimodal analgesia on analgesic outcomes after ACLR, compared to multimodal
      analgesia alone (control). We designated postoperative opioid consumption at 24
      hours as our primary outcome. Secondary outcomes included postoperative opioid
      consumption at 24-48 hours, rest, and dynamic pain severity between 0 and 48
      hours, time to analgesic request, postanesthesia care unit and hospital stay
      durations, patient satisfaction, postoperative nausea and vomiting, functional
      outcomes, and long-term (>1 month) quadriceps strength. Eight randomized
      controlled trials (716 patients) were identified. Five trials compared FNB
      administration to control, and another 3 compared the combination of FNB and LIA
      to LIA alone. Compared to control, adding FNB resulted in modest reductions in 24
      hour opioid consumption in 2 of 3 trials, and improvements in rest pain at 1 hour
      in 1 trial and up to 24 hours in another. In contrast, the combination of FNB and
      LIA, compared to LIA alone, did not reduce opioid consumption in any of the
      trials, but it did improve pain scores at 20 minutes only in 1 trial. The effect
      of FNB on long-term quadriceps strength or function after ACLR was not evaluated
      in the reviewed trials. Contemporary evidence suggests that the benefits of
      adding FNB to multimodal analgesia for ACLR are modest and conflicting, but there
      is no incremental analgesic benefit if the multimodal analgesic regimen included
      LIA. Our findings do not support the routine use of FNB for analgesia in patients
      having ACLR.

PMID- 29596100
TI  - Determination of Geolocations for Anesthesia Specialty Coverage and Standby Call
      Allowing Return to the Hospital Within a Specified Amount of Time.
AB  - BACKGROUND: For emergent procedures, in-house teams are required for immediate
      patient care. However, for many procedures, there is time to bring in a call team
      from home without increasing patient morbidity. Anesthesia providers taking
      subspecialty or backup call from home are required to return to the hospital
      within a designated number of minutes. Driving times to the hospital during the
      hours of call need to be considered when deciding where to live or to visit
      during such calls. Distance alone is an insufficient criterion because of
      variable traffic congestion and differences in highway access. We desired to
      develop a simple, inexpensive method to determine postal codes surrounding
      hospitals allowing a timely return during the hours of standby call. METHODS:
      Pessimistic travel times and driving distances were calculated using the Google
      distance matrix application programming interface for all N= 136 postal codes
      within 60 great circle ("straight line") miles of the University of Miami
      Hospital (Miami, FL) during all 108 weekly standby call hours. A postal code was
      acceptable if the estimated longest driving time to return to the hospital was
      <=60 minutes (the anesthesia department's service commitment to start an urgent
      case during standby call). Linear regression (with intercept = 0) minimizing the
      mean absolute percentage difference between the distances (great circle and
      driving) and the pessimistic driving times to return to the hospital was
      performed among all 136 postal codes. Implementation software written in Python
      is provided. RESULTS: Postal codes allowing return to the studied hospital within
      the specified interval were identified. The linear regression showed that driving
      distances correlated poorly with the longest driving time to return to the
      hospital among the 108 weekly call hours (mean absolute percentage error = 25.1%
      +/- 1.7% standard error [SE]; N = 136 postal codes). Great circle distances also
      correlated poorly (mean absolute percentage error = 28.3% +/- 1.9% SE; N = 136).
      Generalizability of the method was determined by successful application to a
      different hospital in a rural state (University of Iowa Hospital). CONCLUSIONS:
      The described method allows identification of postal codes surrounding a hospital
      in which personnel taking standby call could be located and be able to return to
      the hospital during call hours on every day of the week within any specified
      amount of time. For areas at the perimeter of the acceptability, online distance
      mapping applications can be used to check driving times during the hours of
      standby call.

PMID- 29596101
TI  - Intravenous Acetaminophen Does Not Reduce Inpatient Opioid Prescription or Opioid
      Related Adverse Events Among Patients Undergoing Spine Surgery.
AB  - BACKGROUND: Having entered the US market relatively recently, the perioperative
      role of intravenous acetaminophen (ivAPAP) remains to be established for several
      surgeries. Using national data, we therefore assessed current utilization and
      whether it reduces inpatient opioid prescription and opioid-related side effects
      in a procedure with relatively high opioid utilization. METHODS: Patients
      undergoing a lumbar/lumbosacral spinal fusion (n = 117,269; 2011-2014) were
      retrospectively identified in a nationwide database and categorized by the amount
      and timing of ivAPAP administration (1 or >1 dose on postoperative day [POD] 0,
      1, or 1+). Multivariable models measured associations between ivAPAP utilization
      categories and opioid prescription and perioperative complications; odds ratios
      (or % change) and 95% confidence intervals are reported. RESULTS: Overall, ivAPAP
      was used in 18.9% (n = 22,208) of cases of which 1 dose on POD 0 was the most
      common (73.6%; n = 16,335). After covariate adjustment, use of ivAPAP on POD 0
      and 1 was associated with minimal changes in opioid prescription, length and cost
      of hospitalization particularly favoring >1 ivAPAP dose with a modestly (-5.2%,
      confidence interval, -7.2% to -3.1%; P < .0001) decreased length of stay. Use of
      ivAPAP did not coincide with a consistent pattern of significantly reduced odds
      for complications. In comparison, the most commonly used nonopioid analgesic,
      pregabalin/gabapentin, did demonstrate reduced opioid prescription combined with
      lower complication risk. CONCLUSIONS: We could not show that perioperative ivAPAP
      reduces inpatient opioid prescription with subsequent reduced odds for adverse
      outcomes. It remains to be determined if and under what circumstances ivAPAP has
      a meaningful clinical role in everyday practice.

PMID- 29596102
TI  - Clonidine Effect on Pain After Cesarean Delivery: A Randomized Controlled Trial
      of Different Routes of Administration.
AB  - BACKGROUND: Intrathecal clonidine prolongs spinal anesthesia. We evaluated the
      effects of the addition of intrathecal or intravenous clonidine (75 ug) to
      standard cesarean delivery spinal anesthesia on postoperative pain and neonatal
      outcomes. METHODS: In a randomized, placebo-controlled, double-blind trial, 64
      women scheduled for elective cesarean delivery under spinal anesthesia were
      randomly allocated and compared among 3 groups: intrathecal clonidine 75 ug,
      intravenous clonidine 75 ug, and placebo. The primary outcome was acute
      postoperative pain. A sample size of 26 individuals per group (N = 78) was
      planned. RESULTS: From April 2015 to April 2016, 64 women were analyzed (14
      excluded). No differences in postoperative pain scores were found (Numerical
      Verbal Scale for pain at movement at 24 hours of postcesarean delivery: 4.53 +/-
      3.0 vs 4.45 +/- 2.73 vs 3.93 +/- 3.07 for control, intrathecal, and intravenous,
      respectively, P = .771). Intrathecal and intravenous clonidine led to more
      sedation, in comparison to the control group, during the intraoperative period
      (Richmond Agitation and Sedation Scale: -0.3 +/- 0.47 vs -1 +/- 0.53 vs -0.73 +/-
      0.45 for control, intrathecal, and intravenous, respectively, overall P < .001;
      Dunn correction: P < .001 for intrathecal versus control; P = .021 for
      intravenous versus control; and P = .208 for intrathecal versus intravenous).
      CONCLUSIONS: Intrathecal or intravenous clonidine had no effect on postoperative
      pain after cesarean delivery. Both intrathecal and intravenous clonidine caused
      more sedation.

PMID- 29596103
TI  - Changes in International Normalized Ratios After Plasma Transfusion of Varying
      Doses in Unique Clinical Environments.
AB  - BACKGROUND: Plasma transfusion is commonly performed for the correction of
      abnormal coagulation screening tests. The goal of this investigation was to
      assess the relationship between the dose of plasma administered and changes in
      coagulation test results in a large and diverse cohort of patients with varying
      levels of coagulation abnormalities and comorbid disease and in a variety of
      clinical settings. METHODS: In this single-center historical cohort study, all
      plasma transfusion episodes in adult patients with abnormal coagulation screening
      tests were extracted between 2011 and 2015. The primary outcome was the
      proportion of patients attaining normal posttransfusion international normalized
      ratio (INR <= 1.1) with secondary outcomes including the proportion of patients
      attaining partial normalization of INR (INR <= 1.5) or at least 50% normalization
      in pretransfusion values with respect to an INR of 1.1. RESULTS: In total, 6779
      unique patients received plasma with a median (quartiles) pretransfusion INR of
      1.9 (1.6-2.5) and a median transfusion volume of 2 (2-3) units. The majority
      (85%) of transfusions occurred perioperatively, with 20% of transfusions
      administered prophylactically before a procedure. The median decrease in INR was
      0.4 (0.2-0.8). Complete INR normalization was obtained in 12%. Reductions in INR
      were modest with pretransfusion INR values <3. Patients receiving >=3 units of
      plasma were more likely to achieve at least 50% normalization in INR than those
      receiving <=2 units (68% vs 60%; P < .001). CONCLUSIONS: Changes in INR after
      plasma transfusion were modest at typically used clinical doses, particularly in
      those with less severely deranged baseline coagulation screening tests. Further
      studies are necessary to assess the relationships between plasma-mediated changes
      in INR and clinical outcomes.

PMID- 29596104
TI  - Simulation to Prepare Graduate Nursing Students for Clinical Faculty Role.
AB  - Limited clinical sites and faculty to teach graduate students to be undergraduate
      clinical faculty have led to the exploration of innovative teaching strategies.
      This article describes and evaluates a simulation experience to supplement
      didactic learning about best clinical teaching practices within a graduate
      nursing course. Scenarios were created to simulate complex teaching situations
      with a patient, an undergraduate nursing student, and a clinical faculty member.
      Evaluations were positive regarding knowledge, performance, self-confidence,
      critical thinking, and satisfaction. Results of this project support the use of
      simulation in the preparation of graduate nursing students to become clinical
      faculty.

PMID- 29596105
TI  - Attention Health Care Leaders: Literature Review Deems Baccalaureate Nurses
      Improve Patient Outcomes.
AB  - AIM: This review of studies conducted since the 2011 publication of the Institute
      of Medicine (IOM) report "The Future of Nursing: Leading Change, Advancing
      Health" evaluates the current state of evidence showing an association between an
      increased ratio of BSN-prepared nursing staff and improved patient outcomes.
      BACKGROUND: The IOM established a nationwide goal to increase the number of BSN
      nurses to 80 percent by 2020 to meet the challenges seen in today's health care
      environment. METHOD: The literature search included a five-year (2011-2016) span
      following the initial release of the IOM report. RESULTS: Mortality, failure to
      rescue, and readmission rates all decrease as the proportion of BSN nurses is
      increased in a nursing staffing ratio. CONCLUSION: It is the recommendation of
      this project that nurse leaders and organizations support the findings of this
      literature review and the IOM BSN recommendation.

PMID- 29596106
TI  - Recombinant Human Soluble Thrombomodulin Contributes to Reduced Mortality in
      Sepsis Patients with Severe Respiratory Failure: A Retrospective Observational
      Study Using a Multicenter Dataset.
AB  - BACKGROUND: Recombinant human soluble thrombomodulin (rhTM) is a novel class
      therapeutic agent for managing disseminated intravascular coagulation. The
      progression of severe respiratory failure may be related to intra-alveolar
      coagulation/fibrinolytic disorders. We aimed to determine the efficacy of rhTM in
      treating sepsis patients with severe respiratory failure. METHODS: We performed a
      retrospective observational study using an existing dataset collected from 42
      intensive care units (ICUs) in Japan. Of 3195 patients with severe sepsis or
      septic shock from the dataset, we selected sepsis patients with severe
      respiratory failure, and compared patient outcomes based on the administration of
      rhTM (rhTM group and no rhTM group). Propensity score analysis was performed
      between the 2 groups. Outcomes of interest were ICU mortality, hospital
      mortality, and ventilator-free days (VFDs). RESULTS: In this study, 1180 patients
      (rhTM, n = 356; no rhTM, n = 824) were analyzed. After adjusting for baseline
      imbalances with propensity-score matching, the survival-time analysis revealed a
      significant difference between the 2 groups (hazard ratio, 0.654; 95% confidence
      interval, 0.439-0.974, P = 0.03). ICU mortality was lower in the rhTM group
      (rhTM: 22.1% (33/149) vs. no rhTM: 36.2% (54/149), P = 0.01). Hospital mortality
      was also lower in the rhTM group (35.6% (53/149) vs. 49.7% (74/149), P = 0.02).
      VFDs trended to be higher in the rhTM group than the no rhTM group. (12.8 +/-
      10.1 days vs. 10.6 +/- 10.6 days, P = 0.09). CONCLUSIONS: Administration of rhTM
      was positively correlated with a reduction in mortality in sepsis patients with
      severe respiratory failure.

PMID- 29596107
TI  - TMC120 displayed potent cytotoxic effect on human cervical carcinoma through
      enhancing the polymerization of microtubules.
AB  - OBJECTIVE: In the post-HAART era, the incidence of some AIDS-defining cancers
      declined markedly likely reflecting HAART-related improvements in immunity,
      whereas incidence of some cancers such as cervical cancer has not been affected.
      Therefore, it is valuable to find whether antiretroviral drugs or prophylactic
      microbicides could treat or prevent these cancers, especially the cervical
      cancer. DESIGN: We screened the anti-HIV drugs, approved or in phase III clinical
      trials, to identify a potential anticancer drug candidate. METHODS: We chose
      cervical HeLa and SiHa cancer cells and focused on studying the antitumor effects
      in vitro and in vivo. Cell proliferation was measured by MTT assay, the cytotoxic
      effect was obtained through apoptosis as evidenced by Annexin V flow cytometry
      assay because of the arresting of cancer cells in G2/M phase of cell cycle. Nude
      mice xenograft model was performed to detect the antitumor effect in vivo.
      RESULTS: TMC120 was identified as a potential anticancer drug candidate. TMC120
      displayed potent cytotoxic effect on various human cancer cells, including
      cervical carcinoma cell line HeLa and SiHa. Further mechanism study showed that
      TMC120 enhanced the polymerization of microtubules, which was followed by mitotic
      arrest, as well as abnormal mitotic spindles. TMC120 also substantially retarded
      the growth rate of the tumor in vivo. CONCLUSION: TMC120 is a potential
      chemoprophylactic and therapeutic agent for cervical cancers in a manner similar
      to paclitaxel, and could be suitable for helping healthy women to prevent HIV
      infection and cervical cancer.

PMID- 29596108
TI  - Hepatocellular carcinoma after sustained virological response with interferon
      free regimens in HIV/hepatitis C virus-coinfected patients.
AB  - OBJECTIVE: To assess the possible association between the use of direct antiviral
      agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C
      virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases
      in HIV-infected patients from 32 centers from Spain. Three analyses were
      performed: the proportion of HCC cases after sustained virological response (SVR)
      and the evolution of this proportion over time, the frequency of HCC after SVR in
      HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence
      after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two
      (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR.
      Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN
      based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the
      43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand,
      three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis
      achieved SVR in the cohort. The frequency of HCC after SVR declined from 15%
      among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those
      cured with DAA with and without IFN, respectively. In patients with previous HCC
      treated with curative therapies, HCC recurrence occurred in two (25%) out of
      eight patients treated with IFN-based regimens and four (21%) out of 19 treated
      with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence
      after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected
      patients. DAA do not seem to impact on HCC recurrence in the short-term among
      those with previously treated HCC.

PMID- 29596109
TI  - Sexual risk behaviour trajectories among MSM at risk for HIV in Amsterdam, the
      Netherlands.
AB  - OBJECTIVE: Sexual risk behaviour changes during a person's life course. Insights
      in sexual risk behaviour trajectories of MSM may provide starting points for the
      timing of HIV prevention methods. We aimed to study longitudinal trajectories of
      sexual risk behaviour predictive of HIV acquisition from sexual debut onwards.
      DESIGN: A longitudinal study among 815 HIV-negative participants of the Amsterdam
      Cohort Studies (ACS) who completed extensive questionnaires about their sexual
      behaviour every 6 months between 2007 and 2017. METHODS: A comprehensive
      behavioural risk score predictive of HIV seroconversion was developed. On the
      basis of this risk score, linear trajectories of sexual risk behaviour and MSM
      group membership were estimated using latent class growth mixture modelling.
      Associations between longitudinal trajectories and demographic and psychosocial
      factors were examined. RESULTS: Three trajectories of sexual risk behaviour were
      identified, which were labelled Low risk (90.3% of the sample), Falling high risk
      (6.5%) and Rising high risk (3.3%). MSM following the Falling high risk (20.5%)
      and Rising high risk (25.0%) trajectories were more likely to acquire HIV during
      follow-up. The Falling high risk trajectory was associated with younger age at
      sexual debut, fewer steady partnerships and high percentages of substance use.
      The Rising high-risk trajectory was associated with increasing percentages of
      substance use over time. CONCLUSION: MSM follow different trajectories of
      changing sexual risk behaviour over time. Early identification of MSM following a
      trajectory of falling or rising high-risk behaviour and adequate timing of
      individual-based preventive interventions may reduce HIV transmission.

PMID- 29596110
TI  - Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed
      uninfected children.
AB  - OBJECTIVES: To compare distributions of serum cardiac and inflammatory biomarkers
      between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected
      (PHEU) children, to evaluate their associations with echocardiographic measures,
      and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity
      measures. DESIGN: Cross-sectional analysis of temporally paired serum samples for
      biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV
      and PHEU youth. METHODS: Serum samples were analyzed among 402 youth in the PHACS
      Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs
      cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide
      (NT-proBNP, a myocardial stress marker), and inflammatory markers [high
      sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18,
      tumor necrosis factor-alpha (TNF-alpha), and soluble TNF receptor II (sTNF-RII)].
      Echocardiograms were centrally measured and parameters converted to z cores to
      account for differences in age and body size. RESULTS: Compared with PHEU (N =
      156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of
      sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with
      higher left ventricular (LV) wall stress and lower LV function and LV mass in the
      two groups. Among PHIV youth, the biomarkers were more strongly associated with
      current rather than historical immunologic and virologic status. CONCLUSION: PHEU
      and PHIV have modest, significant differences in serum levels of specific
      inflammatory and active myocardial injury biomarkers. Higher biomarker levels
      were associated with lower LV mass and shifts in LV structure. Further study is
      warranted on the longitudinal role of cardiac and inflammatory biomarkers for
      targeting interventions among PHIV and PHEU youth.

PMID- 29596113
TI  - Development and Feasibility of an Interactive Smartphone App for Early Assessment
      and Management of Symptoms Following Pancreaticoduodenectomy.
AB  - BACKGROUND: Patients who have undergone pancreaticoduodenectomy because of
      pancreatic cancer experience distressing symptoms and unmet supportive care needs
      after discharge. To meet these needs, we have developed a mobile health app
      (Interaktor) for daily assessment of symptoms and access to self-care advice that
      includes a risk assessment model for alerts with real-time interactions with
      professionals. OBJECTIVE: The study aim was to develop and test a version of the
      Interaktor app adapted for patients who have undergone pancreaticoduodenectomy.
      METHODS: The app was developed and tested for feasibility in 6 patients during 4
      weeks. One nurse monitored and responded to alerts. Logged data from the app were
      collected, and all participants were interviewed about their experiences.
      RESULTS: Adherence to reporting daily was 84%. Alerts were generated in 41% of
      the reports. The patients felt reassured and cared for and received support for
      symptom management. The app was easy to use, had relevant content, and had few
      technical problems, although suggestions for improvement were given. CONCLUSIONS:
      The daily reporting of symptoms and having access to a nurse in real time in the
      case of an alarming symptom seem to enhance symptom management and render a
      feeling of security in patients. Some modifications of the app are needed before
      use in a larger sample. IMPLICATIONS FOR PRACTICE: Daily reporting of symptoms
      after pancreaticoduodenectomy enhances symptom management, self-care, and
      participation without being a burden to patients, indicating that mobile health
      can be used in clinical practice by patients with poor prognosis who experience
      severe symptoms.

PMID- 29596114
TI  - ACUTE MACULAR NEURORETINOPATHY IN SUSAC SYNDROME: A NEW ASSOCIATION.
AB  - PURPOSE: To report a case of acute macular neuroretinopathy in a patient with
      Susac syndrome. METHODS: Case report. RESULTS: A 39-year-old male patient
      presented with severe headache, photopsias, and a sudden onset of hearing loss in
      the right ear. Fluorescein angiography of the right eye revealed multiple branch
      retinal artery occlusions. Clinical presentation of encephalopathy, hearing loss,
      and branch retinal artery occlusions, along with characteristic magnetic
      resonance imaging findings, led to a diagnosis of Susac syndrome. Despite
      aggressive immunosuppression for four months, the patient later presented with
      acute macular neuroretinopathy in the left eye. CONCLUSION: Acute macular
      neuroretinopathy and Susac is a new association of two well-defined disorders.
      The concurrence of both disorders supports retinal ischemia as the proximate
      cause of acute macular neuroretinopathy and inflammation as a potential etiology.

PMID- 29596112
TI  - Vagal dysfunction and small intestinal bacterial overgrowth: novel pathways to
      chronic inflammation in HIV.
AB  - OBJECTIVE: Chronic inflammation in HIV-infected individuals drives disease
      progression and the development of comorbidities, despite viral suppression with
      combined antiretroviral therapy. Here, we sought evidence that vagal dysfunction,
      which occurs commonly as part of HIV-associated autonomic neuropathy, could
      exacerbate inflammation through gastrointestinal dysmotility, small intestinal
      bacterial overgrowth (SIBO), and alterations in patterns of soluble immune
      mediators. DESIGN: This is a cross-sectional observational study. METHODS: Forty
      participants on stable combined antiretroviral therapy with gastrointestinal
      symptoms, and no causes for vagal or gastrointestinal dysfunction other than HIV,
      underwent autonomic testing, hydrogen/methane breath testing for SIBO, and
      gastric emptying scintigraphy. A panel of 41 cytokines, high-mobility group box
      1, and markers of bacterial translocation (lipopolysaccharide) and
      monocyte/macrophage activation (sCD14 and sCD163) were tested in plasma. RESULTS:
      We found that participants with vagal dysfunction had delayed gastric emptying
      and higher prevalence of SIBO. SIBO was associated with IL-6, but not sCD14;
      lipopolysaccharide could not be detected in any participant. We also found
      alteration of cytokine networks in participants with vagal dysfunction, with
      stronger and more numerous positive correlations between cytokines. In the vagal
      dysfunction group, high mobility group box 1 was the only soluble mediator
      displaying strong negative correlations with other cytokines, especially those
      cytokines that had numerous other strong positive correlations. CONCLUSION: The
      current study provides evidence that the vagal component of HIV-associated
      autonomic neuropathy is associated with changes in immune and gastrointestinal
      function in individuals with well treated HIV. Further study will be needed to
      understand whether therapies targeted at enhancing vagal function could be of
      benefit in HIV.

PMID- 29596115
TI  - Sensitization of recombinant human tumor necrosis factor-related apoptosis
      inducing ligand-resistant malignant melanomas by quercetin.
AB  - Malignant melanoma is the most commonly diagnosed skin cancer associated with a
      high rate of metastasis. Low-stage melanoma is easily treated, but metastatic
      malignant melanoma is an extremely treatment-resistant malignancy with low
      survival rates. The application of recombinant human tumor necrosis factor
      related apoptosis-inducing ligand (rhTRAIL) for the treatment of metastatic
      malignant melanoma holds considerable promise because of its selective
      proapoptotic activity towards cancer cells and not nontransformed cells.
      Unfortunately, the clinical utilization of rhTRAIL has been terminated due to the
      resistance of many cancer cells to undergo apoptosis in response to rhTRAIL.
      However, rhTRAIL-resistance can be abrogated through the cotreatment with
      compounds derived from 'Mother Nature' such as quercetin that can modulate
      cellular components responsible for rhTRAIL-resistance. Here, we show that
      rhTRAIL-resistant malignant melanomas are sensitized by quercetin. Quercetin
      action is manifested by the upregulation of rhTRAIL-binding receptors DR4 and DR5
      on the surface of cancer cells and by increased rate of the proteasome-mediated
      degradation of the antiapoptotic protein FLIP. Our data provide for a new
      efficient and nontoxic treatment of malignant melanoma.

PMID- 29596117
TI  - Multiple Solid Organ Transplantation in Telomeropathy: Case Series and Literature
      Review.
AB  - BACKGROUND: Solid organ transplantation is a valid treatment option for selected
      patients with organ failure due to an underlying telomeropathy; however, the
      feasibility of multiple-organ transplantation if several organs are compromised
      is unclear. METHODS: We describe 2 patients with telomeropathy due to
      heterozygous telomerase RNA component or telomerase reverse transcriptase
      mutation, who successfully underwent serial or combined liver and lung
      transplantation for concurrent liver fibrosis/cirrhosis and pulmonary fibrosis.
      RESULTS: Despite a challenging posttransplant course, long-term outcomes were
      favorable, with both patients doing fine now, respectively, 12/20 and 24 months
      after multiple-organ transplantation. CONCLUSIONS: To our knowledge, this is the
      first report of multiple solid organ transplantation in documented telomeropathy.
      These cases highlight current difficulties of timely diagnosis, therapeutic
      approach, and postoperative complications in telomeropathy patients in whom
      several organs are affected.

PMID- 29596116
TI  - The Third International Consensus Guidelines on the Management of Cytomegalovirus
      in Solid-organ Transplantation.
AB  - Despite recent advances, cytomegalovirus (CMV) infections remain one of the most
      common complications affecting solid organ transplant recipients, conveying
      higher risks of complications, graft loss, morbidity, and mortality. Research in
      the field and development of prior consensus guidelines supported by The
      Transplantation Society has allowed a more standardized approach to CMV
      management. An international multidisciplinary panel of experts was convened to
      expand and revise evidence and expert opinion-based consensus guidelines on CMV
      management including prevention, treatment, diagnostics, immunology, drug
      resistance, and pediatric issues. Highlights include advances in molecular and
      immunologic diagnostics, improved understanding of diagnostic thresholds,
      optimized methods of prevention, advances in the use of novel antiviral therapies
      and certain immunosuppressive agents, and more savvy approaches to treatment
      resistant/refractory disease. The following report summarizes the updated
      recommendations.

PMID- 29596118
TI  - Treatment of Depression With Duloxetine in Mitochondrial Encephalopathy, Lactic
      Acidosis, and Stroke-Like Episodes.
AB  - The mitochondrial cytopathies are a heterogeneous group of diseases characterized
      by heteroplasmic maternal transmission and selective dysfunction of tissues and
      organs highly dependent on aerobic respiration (eg, skeletal muscle, cardiac
      muscle, and brain). Mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes (MELAS) is a specific subtype of mitochondrial cytopathy
      that is commonly associated with mood disturbances in individuals who survive
      until adulthood. Because of the altered cellular metabolism inherent in MELAS, it
      is often difficult to determine drug dosing, drug choice, and treatment response
      in patients with this rare disease. Historically, management of these patients
      focused on symptomatic relief and supplementation of compounds thought to
      optimize aerobic respiration (specifically, enzyme Co-Q10). We report a case in
      which an adult patient with MELAS and comorbid major depressive disorder
      demonstrated excellent response to the selective serotonin-norepinephrine
      reuptake inhibitor medication duloxetine.

PMID- 29596119
TI  - Normative Data for the Low Anterior Resection Syndrome Score (LARS Score).
AB  - OBJECTIVE: To provide normative data for the Low Anterior Resection Syndrome
      (LARS) score. BACKGROUND: The LARS score is a validated and frequently used tool
      measuring bowel dysfunction after sphincter sparing surgery for rectal cancer.
      The interpretation of LARS score results has previously been limited by the lack
      of normative data. METHODS: An age and sex-stratified random sample of 3440
      citizens from the general population was drawn from the Danish civil registration
      system (age range 20-89 years, 50% females). A brief questionnaire including the
      LARS score and health-related items were distributed electronically or by post.
      RESULTS: A total of 1875 (54.5%) responded, 54.0% were females. In the age group
      50 to 79 years, relevant for most rectal cancer studies, the response rate was
      70.5% (n = 807). In this specific age group, 18.8% of the females and 9.6% of the
      males had a LARS score >=30, corresponding to the LARS score category "major
      LARS" (P = 0.001), and the median (interquartile range) LARS score was 16 (7-26)
      and 11 (4-22), respectively (P < 0.001). Responders with physical disease had a
      statistically significant higher risk of a LARS score >=30, compared with
      responders without any physical disease (odds ratio 2.2, 95% confidence interval
      1.6-2.9, P < 0.001). CONCLUSIONS: A LARS score >=30 (major LARS) is common in the
      general population, especially in the age group 50 to 79 years. Normative data
      for the LARS score are now available and can be taken into account when
      interpreting LARS score results in scientific studies of bowel function after
      rectal cancer treatment.

PMID- 29596120
TI  - Survival in Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy and
      Surgical Resection.
AB  - OBJECTIVE: The aim of the study was to identify the survival of patients with
      locally advanced pancreatic cancer (LAPC) and assess the effect of surgical
      resection after neoadjuvant therapy on patient outcomes. BACKGROUND: An
      increasing number of LAPC patients who respond favorably to neoadjuvant therapy
      undergo surgical resection. The impact of surgery on patient survival is largely
      unknown. MATERIALS AND METHODS: All LAPC patients who presented to the
      institutional pancreatic multidisciplinary clinic (PMDC) from January 2013 to
      September 2017 were included in the study. Demographics and clinical data on
      neoadjuvant treatment and surgical resection were documented. Primary tumor
      resection rates after neoadjuvant therapy and overall survival (OS) were the
      primary study endpoints. RESULTS: A total of 415 LAPC patients were included in
      the study. Stratification of neoadjuvant therapy in FOLFIRINOX-based, gemcitabine
      based, and combination of the two, and subsequent outcome comparison did not
      demonstrate significant differences in OS of 331 non-resected LAPC patients (P =
      0.134). Eighty-four patients underwent resection of the primary tumor (20%),
      after a median duration of 5 months of neoadjuvant therapy. FOLFIRINOX-based
      therapy and stereotactic body radiation therapy correlated with increased
      probability of resection (P = 0.006). Resected patients had better performance
      status, smaller median tumor size (P = 0.029), and lower median CA19-9 values (P
      < 0.001) at PMDC. Patients who underwent surgical resection had significant
      higher median OS compared with those who did not (35.3 vs 16.3 mo, P < 0.001).
      The difference remained significant when non-resected patients were matched for
      time of neoadjuvant therapy (19.9 mo, P < 0.001). CONCLUSIONS: Surgical resection
      of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of
      patients (20%) and is associated with significantly longer median overall
      survival.

PMID- 29596121
TI  - FOOD INSECURITY: A PUBLIC HEALTH CHALLENGE.

PMID- 29596122
TI  - Increasing Hepatitis C Virus Knowledge Through an Evidence-Based Educational
      Intervention.
AB  - Hepatitis C virus infection is the most common chronic blood-borne infection in
      the United States (U.S.). Increasing rates of hepatitis C virus infection among
      drug users present a significant public health problem in the U.S. and globally.
      This article describes the effect an educational intervention on hepatitis C
      virus knowledge. A project was conducted using the Brief Hepatitis C Knowledge
      Scale to assess pre- and post-test intervention knowledge. An educational
      intervention consisting of a video (Hepatitis C: Get the Facts) and a written
      handout, as well as a question-and-answer session, was administered to
      participants at a local health department. Analysis of the data through use of
      descriptive statistics to compare percentage change of the mean from the pretest
      to post-test to 3-week post-test intervention was performed. Results demonstrated
      the use of an educational intervention to be effective in increasing hepatitis C
      virus knowledge. An increase in knowledge regarding hepatitis C virus
      transmission may lead to a decrease in overall hepatitis C virus infection rates
      as well as risky behaviors.

PMID- 29596123
TI  - Fast-Track Recovery Program After Major Liver Resection: A Randomized Prospective
      Study.
AB  - The objective of this study was to compare fast-track (FT) recovery protocol with
      the conventional one in patients treated with major liver resection by evaluating
      perioperative morbidity, length of hospitalization, and readmission rate. Sixty
      two patients suffering from malignant liver tumors were surgically treated from
      May 2012 to April 2014. After randomization, they were prospectively divided into
      two groups: Group A patients (n = 32) followed FT recovery protocol and Group B
      patients (n = 30) were treated with the conventional (CON) protocol.
      Postoperative morbidity, readmission rate, and median hospital stay in the two
      groups were studied. Fast-track protocol was associated with a decreased
      complication (25%, p = .002), whereas the risk of postoperative morbidity was 2.4
      times higher in patients treated with the CON protocol (60%, p = .002).
      Readmission rate was not significantly different between the two groups (6.25%, p
      = .35). Age (p = .382) and body mass index (p = .818) were not a suspending
      factor for following the FT protocol. Overall length of stay (postoperative days)
      in the FT group was (mean +/- SD) 5.75 +/- .5 and in the CON group was 13.5 +/-
      6.7 (p < .001). Fast-track recovery protocol seems to be safe and particularly
      efficient in patients undergoing major liver resections.

PMID- 29596124
TI  - Diverticular Disease: Traditional and Evolving Paradigms.
AB  - Diverticular disease includes diverticulosis, which are sac protrusions of the
      intestinal mucosa, and diverticulitis, inflammation of the diverticula.
      Diverticular disease is listed as one of the top 10 leading physician diagnoses
      for gastrointestinal disorders in outpatient clinic visits in the United States.
      There are several classifications of diverticular disease ranging from
      asymptomatic diverticulosis to diverticulitis with complications. Several
      theories are linked to the development of diverticula which includes the
      physiology of the colon itself, collagen cross-linking, and recently challenged,
      low-fiber intake. The differential diagnoses of lower abdominal pain in addition
      to diverticular disease have overlapping signs and symptoms, which can make a
      diagnosis challenging. Identification of the distinct signs and symptoms of each
      classification will assist the practitioner in making the correct diagnosis and
      lead to appropriate management. The findings from recent studies have changed the
      paradigm of diverticular disease. The purpose of this article is to discuss
      traditional dogma and evolving concepts in the pathophysiology, prevention, and
      management of diverticular disease. Practitioners must be knowledgeable about
      diverticular disease for improved outcomes.

PMID- 29596125
TI  - Diverticular Disease: Traditional and Evolving Paradigms.

PMID- 29596126
TI  - Factors Influencing the Life Experiences of Individuals With Inflammatory Bowel
      Disease.
AB  - Inflammatory bowel disease has a negative impact on individuals perception of
      their health status and is associated with disabling processes that have
      physical, social, and work repercussions. The objectives of this study were to
      describe the life experiences of individuals with Crohn disease and ulcerative
      colitis and to develop a theoretical framework to describe the relationships of
      these diseases with personal and clinical factors. A qualitative study on the
      basis of grounded theory was conducted, involving individual and semistructured
      interviews on the life experiences of 14 adults of different ages with
      inflammatory bowel disease in relapse or inactive phase. The individuals in
      relapse phase and those with a short time since diagnosis had the most negative
      perceptions of their health, and experienced impaired ability for daily
      activities. The life experiences of individuals with inflammatory bowel disease
      were influenced by the time since diagnosis and the disease phase, with no gender
      difference in either factor. The predominant strategy of participants for coping
      with the disease was to pursue normality. According to these findings, nursing
      interventions should focus on the initial adaptation phase and on coping
      strategies during active phases of the disease.

PMID- 29596127
TI  - Effect of Early Postoperative Feeding on the Recovery of Children Post
      Appendectomy.
AB  - The aim of this study was to determine the effect of early postoperative feeding
      on recovery after appendectomy in children. It was undertaken as a multicenter
      study. Patients were randomly assigned to 2 groups, each containing 46 children.
      Postoperatively, liquid and solid food intake and evacuation of first flatus and
      stool were recorded for the intervention and routine care groups. Postoperative
      thirst, hunger, nausea, and pain levels were evaluated at regular intervals using
      the Visual Analogue Scale. Data were obtained as number, mean, and percentage,
      and statistically analyzed using the chi-square test and the 2-sample t test. A
      statistically significant difference was found for both the first evacuation of
      flatus and stool and the length of hospital stay. Patients in the intervention
      group had evacuated flatus and stool earlier and had a shorter hospital stay than
      the control group. In addition, a significant difference was found in hunger
      (48th hour), thirst (36th and 48th hours), and pain (48th hour) levels between
      the intervention and control groups. Early postoperative feeding in children who
      have had an appendectomy affects the occurrence of the first evacuation of flatus
      and stool, the length of hospital stay, and the level of hunger, thirst, and
      pain.

PMID- 29596128
TI  - A Retrospective Study Comparing Polyethylene Glycol-Electrolyte Solution With
      Magnesium Citrate for Treatment of Fecal Disimpaction.
AB  - Fecal disimpaction in the hospital setting may be necessary for a constipated
      child's condition to improve. This study evaluated the efficiency of 2
      disimpaction therapies: nasogastric GoLYTELY (polyethylene glycol-electrolyte
      solution) compared with oral magnesium citrate. Retrospective chart review of 103
      children was conducted to determine the time from the start of the clinic
      cleanout until abdominal radiograph verification of successful stool evacuation.
      The children were in an age range of 1-18 years, with average age of 8 years.
      Forty-five were female and 59 were male. Forty-six (45%) children received
      nasogastric polyethylene glycol-electrolyte and 57 (55%) drank magnesium citrate.
      The children receiving nasogastric polyethylene glycol-electrolyte on average
      required 2.5 enemas, and the children receiving magnesium citrate required 3.0
      enemas. The average time for a nasogastric polyethylene glycol-electrolyte
      cleanout was 5 hours 15 minutes (range: 3 hours 30 minutes to 7 hours) and 5
      hours 30 minutes for magnesium citrate cleanout (range: 2 to 8 hours). Seven
      (15%) children who received nasogastric polyethylene glycol-electrolyte and 6
      (10%) of those who drank magnesium citrate did not achieve clearance of stool on
      the second radiograph. Vomiting was an adverse effect of both medications, and 7
      (12%) children were unable to drink the entire magnesium citrate dose. Both
      methods of disimpaction take the same amount of time. Magnesium citrate can be
      difficult to drink; however, it is less invasive and less costly than nasogastric
      polyethylene glycol-electrolyte.

PMID- 29596129
TI  - Healthcare Transition in Pediatrics and Young Adults With Inflammatory Bowel
      Disease: A Scoping Review.
AB  - The incidence of inflammatory bowel disease has steadily increased in children
      within the last decade. As young adults transition into the adult healthcare
      system, lack of support can lead to disease exacerbations and disease-related
      complications. The purpose of this scoping review was to examine the current
      healthcare transition literature in pediatrics and young adults with inflammatory
      bowel disease, with a particular focus on assessment or screening tools to
      evaluate healthcare transition readiness. Five most relevant databases were
      searched. Of these, 22 articles met the inclusion criteria and key findings from
      these are summarized. The majority of articles focused on adolescents or young
      adults with inflammatory bowel disease and were primarily published in the United
      States. Since 2008, there has been a growing trend in publications of
      inflammatory bowel disease healthcare transition literature. Articles were often
      described as healthcare transition readiness assessment tools, patient outcomes
      following transition, or transition experiences and barriers. An understanding of
      the current literature on the readiness assessment and support strategies is
      required to promote an improved quality of life for pediatric and young adult
      patients living with inflammatory bowel disease.

PMID- 29596130
TI  - Screening Indication Associated With Lower Likelihood of Minor Adverse Events in
      Patients Undergoing Outpatient Colonoscopy.
AB  - We sought to determine, among outpatients at one university hospital endoscopy
      center, rates of self-reported minor adverse events (MAEs) at 2, 14, and 30 days
      postcolonoscopy and to identify predictors of MAEs at Day 2 postcolonoscopy. A
      single-center longitudinal cohort study with follow-ups at Days 2, 14, and 30
      postcolonoscopy was conducted in Montreal, Canada. Baseline self-report data
      included patient age, gender, gastrointestinal discomforts and other discomforts
      in the preceding month, and comorbidity. Intracolonoscopy procedures and the
      method of insufflation were obtained from endoscopy reports. Minor adverse event
      data were obtained by either phone or Internet survey. Multivariate logistic
      regression was used to identify predictors of MAEs at Day 2. Of 705 individuals
      approached, 420 (mean age = 58.7 years; SD = 8.4, 45.7% female) were eligible and
      consented to study participation, and 378 (90%) participated in at least one
      follow-up. At Days 2, 14, and 30, 86 (25.1%), 46 (13.7%), and 13 (3.1%) patients,
      respectively, experienced at least one MAE. At the Day 30 follow-up, 2 (0.53%)
      patients reported having experienced a serious adverse event. The multivariable
      analysis results showed that screening compared with nonscreening colonoscopy was
      protective for MAEs at 2 days (OR = 0.5, 95% CI [0.3, 0.9]). We found that 25% of
      patients experienced at least one MAE at 2 days postcolonoscopy, and screening
      compared with nonscreening colonoscopy patients were half as likely to experience
      these early MAEs. Nurses may use these findings to educate and reassure patients
      about colonoscopy risks. Large, longitudinal multicenter studies are needed to
      corroborate our findings.

PMID- 29596131
TI  - COEXISTENCE OF GASTRIC DIVERTICULUM AND GASTRIC CANCER.

PMID- 29596132
TI  - THE OTHER SIDE OF HEALTHCARE.

PMID- 29596133
TI  - An update on 'dose calibrator' settings for nuclides used in nuclear medicine.
AB  - BACKGROUND: Most clinical measurements of radioactivity, whether for therapeutic
      or imaging nuclides, rely on commercial re-entrant ionization chambers ('dose
      calibrators'). The National Institute of Standards and Technology (NIST)
      maintains a battery of representative calibrators and works to link calibration
      settings ('dial settings') to primary radioactivity standards. Here, we provide a
      summary of NIST-determined dial settings for 22 radionuclides. METHODS: We
      collected previously published dial settings and determined some new ones using
      either the calibration curve method or the dialing-in approach. RESULTS: The dial
      settings with their uncertainties are collected in a comprehensive table.
      CONCLUSION: In general, current manufacturer-provided calibration settings give
      activities that agree with National Institute of Standards and Technology
      standards to within a few percent.

PMID- 29596135
TI  - We want to hear about you!: 2018 Richard Hader Visionary Leader Award.

PMID- 29596134
TI  - Assessing Resident Safety Culture in Six Nursing Homes in Belgium.
AB  - OBJECTIVES: The primary aim was to measure resident safety culture in six nursing
      homes in northern Belgium (Flanders). In addition, differences in safety culture
      perceptions between professions were also examined. Finally, results of the
      present study were compared with the Nursing Home Comparative Database from the
      Agency for Healthcare Research and Quality (USA). METHODS: A cross-sectional
      study was conducted by administering the Nursing Home Survey on Patient Safety
      Culture in six nursing homes in Belgium (Flanders). Each nursing home has 92 to
      170 licensed nursing home beds. Data collection occurred between December 2016
      and January 2017. RESULTS: Highest mean scores were found for "feedback and
      communication about incidents" (mean [SD] = 4.20 [0.58]), "overall perceptions of
      resident safety" (mean [SD] = 4.07 [0.52]), and "supervisor expectations and
      actions promoting resident safety" (mean [SD] = 4.04 [0.70]). The lowest mean
      score was found for "staffing" (mean [SD] = 2.99 [0.61]). In addition,
      managers/supervisors scored significantly higher on all resident safety
      dimensions, with the exception of the dimensions "teamwork" and "supervisor
      expectations and actions promoting resident safety." Finally, the present study
      scored higher on the dimensions "teamwork," "nonpunitive response to mistakes,"
      "handoffs," "feedback and communication about incidents," and "communication
      openness" than the benchmarking data from the Nursing Home Comparative Database.
      CONCLUSIONS: More work is necessary to improve the safety of resident care in
      nursing homes, especially regarding staffing issues and turnover rates. The
      present research findings serve to shine a light on an often-overlooked patient
      population and emphasize the need to develop improvement strategies for
      preventing resident safety incidents in nursing homes.

PMID- 29596136
TI  - Win-win leadership practicums.

PMID- 29596137
TI  - "Keep Calm and Stop the Clot".
AB  - The impact of a nurse-driven change project.

PMID- 29596138
TI  - Nursing Management partners with ANCC's Pathway to Excellence(r) Program.

PMID- 29596139
TI  - Intentional nurse manager rounding and patient satisfaction.

PMID- 29596140
TI  - Rural CNO leadership: A qualitative study.

PMID- 29596141
TI  - How to achieve empirical outcomes in the ED.
AB  - Using transformational leadership and innovative marketing strategies.

PMID- 29596142
TI  - A partnership to assess clinical nurse leadership skills.

PMID- 29596143
TI  - Supporting successful mentoring.
AB  - In the first installment of our two-part series, we discussed organizing a mentor
      program for nurse managers who want to develop their careers. In part 2, we
      examine how nurse managers can assist staff members with their own mentoring
      program.

PMID- 29596145
TI  - Strategies for overcoming language barriers in healthcare.

PMID- 29596144
TI  - The power of gratitude.

PMID- 29596146
TI  - Vortioxetine Disposition in Obesity: Potential Implications for Patient Safety.
AB  - BACKGROUND: Obesity and depression are common comorbid conditions. The objective
      of the study was to evaluate the effect of obesity on the pharmacokinetics of the
      serotonergic antidepressant vortioxetine. METHODS: Vortioxetine pharmacokinetics
      were evaluated in 16 otherwise healthy obese volunteers (mean weight, 119 kg;
      mean body mass index (BMI) 41.8 kg/m) and in 14 normal-weight subjects (mean
      weight, 68 kg; mean BMI, 23.0 kg/m) matched for age. All subjects received a
      single 5-mg oral dose of vortioxetine once daily for 29 days. Pre-dose plasma
      vortioxetine concentrations were measured during the 29 days of dosing, and
      during a 4-week washout period after the last dose. Full 24-hour profiles were
      obtained after the first and last doses. RESULTS: Vortioxetine accumulated
      extensively over the 29 days; the accumulation ratio was not significantly
      different between obese and control groups (means: 5.24 and 4.46, respectively).
      Steady-state concentration (Css) and steady-state clearance also did not differ
      between groups. However mean washout half-life (T1/2) was significantly prolonged
      in obese vs. control subjects (3.26 days vs. 2.21 days, P < 0.01). Up to 89% of
      the individual variability in T1/2 was explained by the product of Css and
      numeric indicators of the degree of obesity. CONCLUSIONS: The half-life of
      vortioxetine washout after discontinuation of therapy is significantly prolonged
      in obese individuals compared to normal weight controls. To avoid a potential
      risk of serotonin syndrome, obese patients who plan to change their medication
      from vortioxetine to a monoamine oxidase inhibitor (MAOI) should extend the time
      between vortioxetine discontinuation and MAOI initiation beyond what is
      recommended in the product label.

PMID- 29596147
TI  - Maternal Antidepressant Use During Pregnancy and the Risk of Attention
      Deficit/Hyperactivity Disorder in Children: A Systematic Review of the Current
      Literature.
AB  - PURPOSE: This study reviewed the current literature examining the potential
      relationship between use of antidepressants during pregnancy and attention
      deficit/hyperactivity disorder (ADHD) in children. METHODS: PubMed was searched
      for English language reports between January 1, 1995, and July 31, 2017, by using
      combinations of the key words pregnancy, antidepressants, selective serotonin
      reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake
      inhibitors (SNRIs), tricyclic antidepressants (TCAs), children, offspring, and
      ADHD. Studies that reported association between ADHD in children and use of
      antidepressant in pregnant women were included in the review. RESULTS: A total of
      7 relevant studies that met the review criteria were examined. The studies
      reported that compared with nonusers adjusted risks of ADHD in children were 1.2
      to 1.6 for the use of any antidepressant, 0.91 to 1.66 for selective serotonin
      reuptake inhibitors, 1.1 to 1.4 for selective serotonin-norepinephrine reuptake
      inhibitors, and 1.1 to 1.8 for tricyclic antidepressants. There was some
      scientific evidences suggesting a connection between antidepressant use during
      all trimesters of pregnancy and increased risk of ADHD in children. In addition,
      the study results suggest that underlying maternal anxiety or depressive
      disorders may also contribute to increased risk of ADHD. IMPLICATIONS: Although
      some studies have suggested a moderately increased risk of ADHD in children with
      maternal antidepressant use during pregnancy, based on limitations and results of
      the studies, this review concluded that there is no strong evidence to suggest a
      causal link.

PMID- 29596149
TI  - Low-Dose Aripiprazole and Risperidone for Treating Problem Behavior in Children
      With Pitt-Hopkins Syndrome.

PMID- 29596148
TI  - Personalized (N-of-1) Trials for Depression: A Systematic Review.
AB  - PURPOSE/BACKGROUND: Personalized (N-of-1) trials are single-patient, crossover
      design trials that may be useful for personalizing the selection of depression
      treatments. We conducted a systematic review of published N-of-1 trials for
      depression to determine the feasibility and suitability of this methodology for
      personalizing depression care. METHODS/PROCEDURES: Electronic databases were
      searched from database inception through October 2016. Studies were selected if
      they enrolled depressed patients, included a within-subject crossover design, and
      systematically assessed depressive symptoms during the N-of-1 trial.
      FINDINGS/RESULTS: Five eligible studies reporting on 47 depressed patients
      (range, 1-18 patients) were identified. Two studies were conducted among adults
      with treatment-resistant depression, 1 study among depressed inpatients, and 2
      studies among patients from special populations (geriatric nursing home, human
      immunodeficiency virus-associated encephalopathy). All studies evaluated the
      effects of pharmacologic treatments (methylphenidate, D-amphetamine, ketamine,
      and sulpiride). Three studies compared an off-label treatment with placebo, 1
      study compared 2 off-label treatments, and 1 study compared escalating doses of
      an off-label treatment with placebo. All 4 studies with more than 1 participant
      demonstrated heterogeneous treatment effects. All studies produced data that
      could personalize treatment selection for individual patients. No studies
      reported on recruitment challenges, compliance with self-tracking, or
      satisfaction with participation. IMPLICATIONS/CONCLUSIONS: The feasibility of N
      of-1 trials for depression was demonstrated for a limited number of second-line
      pharmacologic treatments in treatment-resistant patients or in patients with
      comorbidities that would have excluded them from conventional randomized
      controlled trials. Additional research is needed to determine whether N-of-1
      trials are suitable for improving the selection of depression treatments in
      clinical practice.

PMID- 29596150
TI  - Effects of Intranasal Oxytocin Administration on Sexual Functions in Healthy
      Women: A Laboratory Paradigm.
AB  - PURPOSE: The neuropeptide oxytocin (OXT) has a variety of physiological functions
      in maternal behavior and attachment including sexual behavior. Based on animal
      research and our previous human studies, we set out to investigate intranasal
      administration of OXT and hypothesized that OXT should be able to modulate sexual
      function in women. METHODS: In a double-blind, placebo-controlled, crossover
      laboratory setting, the acute effects of intranasal administered OXT (24
      international units) on sexual drive, arousal, orgasm, and refractory aspects of
      sexual behavior were analyzed in 27 healthy females (mean age +/- SD, 27.52 +/-
      8.04) together with physiological parameters using vaginal photoplethysmography.
      FINDINGS: Oxytocin administration showed no effect on subjective sexual
      parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters
      (vaginal photoplethysmography amplitude and vaginal blood volume) showed a
      response pattern towards sexual arousal but were not affected by OXT.
      IMPLICATIONS: Using a well-established laboratory paradigm, we did not find that
      intranasal OXT influences female sexual parameters. Also, sexual drive and other
      functions were not affected by OXT. These findings indicate that OXT is not able
      to significantly increase subjective and objective parameters of sexual function
      in a setting with high internal validity; however, this might be different in a
      more naturalistic setting.

PMID- 29596151
TI  - A novel online fluorescence method for in-vivo measurement of hydrogen peroxide
      during oxidative stress produced in a temporal lobe epilepsy model.
AB  - Status epilepticus (SE) can result in an overproduction of hydrogen peroxide
      (H2O2), which contributes to oxidative stress and brain injury during different
      phases of epileptogenesis and seizures. In this study, we measured the
      extracellular H2O2 concentration in the rat hippocampus in a temporal lobe
      epilepsy model. A new fluorescent technique for measuring H2O2 in vivo
      simultaneously with electroencephalography recording was tested. The method
      consists of mixing microdialysate with an enzymatic reactor to produce a
      fluorescent compound. The fluorescence intensity was measured every second and
      was proportional to the H2O2 concentration. The results showed that H2O2 was
      released during SE; we detected a significant increase of up to five times over
      the baseline value that correlated with changes in electrical activity. We also
      observed that H2O2 was produced for days after SE and was associated with
      continuous neuronal death and seizure generation. Therefore, we monitored H2O2 48
      h and 15 days after SE, observing increases of up to 96 and 124%, respectively,
      accompanied by changes in electrical activity with spontaneous discharges of
      large amplitude. These changes may reflect the oxidative stress generated during
      epileptogenesis that remains during the chronic period (458% increased) with the
      presence of large spikes, indicating that the H2O2 could also participate in the
      generation and maintenance of spontaneous recurrent seizures. There are no
      previous reports on the detection of H2O2 at this temporal resolution; thus, this
      study contributes a novel technique for studying and understanding
      epileptogenesis to develop new antioxidant strategies for the treatment of
      temporal lobe epilepsy.

PMID- 29596152
TI  - Upregulation of P2X2 and P2X3 receptors in rats with hyperalgesia induced by
      heroin withdrawal.
AB  - Drug dependence and withdrawal syndrome induced by abrupt cessation of opioid
      administration remain a severe obstacle in the clinical treatment of chronic pain
      and opioid drug addiction. One of the key symptoms during opioid withdrawal is
      hyperalgesia. The mechanism of opioid withdrawal-induced hyperalgesia remains
      unclear. P2X2 and P2X3 receptors, members of P2X receptor subunits, act as the
      integrator of multiple forms of noxious stimuli and play an important role in
      nociception transduction of chronic neuropathic and inflammatory pain. The
      process of P2X2 and P2X3 receptor antagonism inhibits inflammatory hyperalgesia,
      involving the spinal opioid system. However, the role of P2X receptors involved
      in opioid withdrawal-induced hyperalgesia has seldom been discussed. To explore
      the role of P2X2 and P2X3 receptors in the opioid-induced hyperalgesia, heroin
      self-administration rats were adopted, and the thermal and mechanical nociceptive
      thresholds were evaluated using the paw withdrawal test after abstinence from
      heroin for 8 days. In addition, the expressions of P2X2 and P2X3 receptors in
      dorsal root ganglia were analyzed by immunofluorescence. The results showed that
      after 8 days of abstinence, heroin self-administration rats showed thermal
      hyperalgesia and mechanical allodynia. Meanwhile, the expressions of the P2X2 and
      P2X3 receptors in dorsal root ganglia were increased. These results suggest that
      upregulation of P2X2 and P2X3 receptors might partially play a role in heroin
      withdrawal-induced hyperalgesia.

PMID- 29596153
TI  - The neural underpinnings of music listening under different attention conditions.
AB  - Most studies examining the neural underpinnings of music listening have no
      specific instruction on how to process the presented musical pieces. In this
      study, we explicitly manipulated the participants' focus of attention while they
      listened to the musical pieces. We used an ecologically valid experimental
      setting by presenting the musical stimuli simultaneously with naturalistic film
      sequences. In one condition, the participants were instructed to focus their
      attention on the musical piece (attentive listening), whereas in the second
      condition, the participants directed their attention to the film sequence
      (passive listening). We used two instrumental musical pieces: an electronic pop
      song, which was a major hit at the time of testing, and a classical musical
      piece. During music presentation, we measured electroencephalographic
      oscillations and responses from the autonomic nervous system (heart rate and high
      frequency heart rate variability). During passive listening to the pop song, we
      found strong event-related synchronizations in all analyzed frequency bands
      (theta, lower alpha, upper alpha, lower beta, and upper beta). The
      neurophysiological responses during attentive listening to the pop song were
      similar to those of the classical musical piece during both listening conditions.
      Thus, the focus of attention had a strong influence on the neurophysiological
      responses to the pop song, but not on the responses to the classical musical
      piece. The electroencephalographic responses during passive listening to the pop
      song are interpreted as a neurophysiological and psychological state typically
      observed when the participants are 'drawn into the music'.

PMID- 29596154
TI  - Altered intrinsic activity and functional connectivity in two animal models with
      opposing fear memories.
AB  - Post-traumatic stress disorder and sepsis-associated encephalopathy are two
      common neuropsychiatric disorders, but to some extent with opposing cognitive
      performance. However, the neural mechanisms underlying these two different
      phenomena remain poorly understood. In our study, the amplitude of low-frequency
      fluctuations (ALFF) of spontaneous blood oxygen level-dependent signals was used
      to assess regional disturbances in two animal models with opposing cognitive
      performance, namely post-traumatic stress disorder and sepsis-associated
      encephalopathy. Then, we examined whether the memory-relevant brain regions with
      impaired ALFF altered functional connectivity within the whole brain. Here, we
      showed that lipopolysaccharide challenge and footshock induced significantly
      different cognitive performance. We found significant group differences in ALFF
      in the bilateral dentate gyrus. In addition, our study showed that footshocks
      induced a significant decrease in functional connectivity between the left
      dentate gyrus and the visual cortex compared with the lipopolysaccharide group.
      Notably, cognitive performance was associated with ALFF values in the right
      dentate gyrus. In conclusion, our data suggested that damaged regional
      spontaneous activity and abnormal functional connectivity might be differently
      involved in two opposing fear memories.

PMID- 29596155
TI  - miR-221 alleviates the inflammatory response and cell apoptosis of neuronal cell
      through targeting TNFAIP2 in spinal cord ischemia-reperfusion.
AB  - This study aimed to examine the role of miR-221 in inflammatory response and
      apoptosis of neuronal cells after spinal cord ischemia/reperfusion (I/R) injury.
      Blood samples were obtained from 20 I/R patients and that of 20 healthy
      individuals were used as a control. AGE1.HN and SY-SH-5Y neuronal cell lines
      subjected to oxygen-glucose deprivation (OGD) stress were used in cell
      experiments. Real-time PCR and western blot were used to evaluate the expression
      of miR-221, tumor necrosis factor-alpha, and TNFAIP2. TUNEL assay analyzed cell
      apoptosis. I/R patients had lower serum levels of miR-221 than healthy controls.
      In OGD-AGE1.HN and SY-SH-5Y cells, miR-221 was significantly downregulated and
      TNFAIP2 mRNA and protein were upregulated; meanwhile, both proinflammatory
      cytokine tumor necrosis factor-alpha and anti-inflammation cytokine interleukin-6
      were elevated and the percentage of apoptotic cells was increased. This
      inflammatory response and cell apoptosis induced by OGD stress were attenuated by
      miR-221 overexpression and enhanced by miR-221 knockdown. TNFAIP2 is a target
      gene for miR-221 and could be regulated negatively by the miR-221 mimic or the
      miR-221 inhibitor with or without OGD stress. Accordingly, TNFAIP2 overexpression
      reversed the inflammatory response and cell apoptosis induced by miR-221 under
      OGD stress. Downregulation of miR-221 occurs in spinal cord I/R injury and in
      cell lines subjected to oxygen-glucose deprivation. miR-221 regulates the
      inflammatory response and apoptosis of neuronal cells through its impact on
      TNFAIP2.

PMID- 29596156
TI  - Face-sensitive P1 and N170 components are related to the perception of two
      dimensional and three-dimensional objects.
AB  - Studies investigating event-related potentials have reported on face-sensitive P1
      and N170 components, as well as object-related N170 components. Face-sensitive
      N170 is also sensitive to face inversion, which has been defined as the face
      inversion effect. This study aimed to directly compare the relationship between
      face-sensitive N170 during face perception (upright and inverted faces) and
      object-related N170 during object perception (two-dimensional and three
      dimensional objects). More specifically, the purpose was to clarify whether face
      sensitive P1 and N170 components are related to the perception of two-dimensional
      and three-dimensional objects. Electroencephalography was performed in
      participants who were shown one of the four types of stimuli: upright faces,
      inverted faces, two-dimensional objects, or three-dimensional objects. The
      results revealed that the latency of P1 for three-dimensional objects was
      significantly longer than that for two-dimensional objects, the latency of N170
      for three-dimensional objects was significantly longer than that for two
      dimensional objects, and the latency of N170 for inverted faces was significantly
      longer than that for upright faces. These findings suggest that face-sensitive P1
      and N170 components are related to the perception of two-dimensional and three
      dimensional objects. Moreover, the results suggest that, similar to the face
      inversion effect of face-sensitive N170 affected by mental rotation of the face,
      the object-related N170 of three-dimensional objects was affected by the mental
      rotation of two-dimensional objects. This suggests the novel possibility that
      face-sensitive P1 and N170 components can be used as an index for the perception
      of two-dimensional and three-dimensional objects.

PMID- 29596157
TI  - Machine-learned analysis of the association of next-generation sequencing-based
      human TRPV1 and TRPA1 genotypes with the sensitivity to heat stimuli and
      topically applied capsaicin.
AB  - Heat pain and its modulation by capsaicin varies among subjects in experimental
      and clinical settings. A plausible cause is a genetic component, of which TRPV1
      ion channels, by their response to both heat and capsaicin, are primary
      candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and
      carry genetic variants reported to modulate heat pain sensitivity. To address the
      role of these candidate genes in capsaicin-induced hypersensitization to heat,
      pain thresholds acquired before and after topical application of capsaicin and
      TRPA1/TRPV1 exomic sequences derived by next-generation sequencing were assessed
      in n = 75 healthy volunteers and the genetic information comprised 278 loci.
      Gaussian mixture modeling indicated 2 phenotype groups with high or low capsaicin
      induced hypersensitization to heat. Unsupervised machine learning implemented as
      swarm-based clustering hinted at differences in the genetic pattern between these
      phenotype groups. Several methods of supervised machine learning implemented as
      random forests, adaptive boosting, k-nearest neighbors, naive Bayes, support
      vector machines, and for comparison, binary logistic regression predicted the
      phenotype group association consistently better when based on the observed
      genotypes than when using a random permutation of the exomic sequences. Of note,
      TRPA1 variants were more important for correct phenotype group association than
      TRPV1 variants. This indicates a role of the TRPA1 and TRPV1 next-generation
      sequencing-based genetic pattern in the modulation of the individual response to
      heat-related pain phenotypes. When considering earlier evidence that topical
      capsaicin can induce neuropathy-like quantitative sensory testing patterns in
      healthy subjects, implications for future analgesic treatments with transient
      receptor potential inhibitors arise.

PMID- 29596159
TI  - Associations between onset of effort-reward imbalance at work and onset of
      musculoskeletal pain: analyzing observational longitudinal data as pseudo-trials.
AB  - Existing evidence of an association between effort-reward imbalance (ERI) at work
      and musculoskeletal pain is limited, preventing reliable conclusions about the
      magnitude and direction of the relation. In a large longitudinal study, we
      examined whether the onset of ERI is associated with subsequent onset of
      musculoskeletal pain among those free of pain at baseline, and vice versa,
      whether onset of pain leads to onset of ERI. Data were from the Swedish
      Longitudinal Occupational Survey of Health (SLOSH) study. We used responses from
      3 consecutive study phases to examine whether exposure onset between the first
      and second phases predicts onset of the outcome in the third phase (N = 4079).
      Effort-reward imbalance was assessed with a short form of the ERI model. Having
      neck-shoulder and low back pain affecting life to some degree in the past 3
      months was also assessed in all study phases. As covariates, we included age,
      sex, marital status, occupational status, and physically strenuous work. In the
      adjusted models, onset of ERI was associated with onset of neck-shoulder pain
      (relative risk [RR] 1.51, 95% confidence interval [CI] 1.21-1.89) and low back
      pain (RR 1.21, 95% CI 0.97-1.50). The opposite was also observed, as onset of
      neck-shoulder pain increased the risk of subsequent onset of ERI (RR 1.36, 95% CI
      1.05-1.74). Our findings suggest that when accounting for the temporal order, the
      associations between ERI and musculoskeletal pain that affects life are
      bidirectional, implying that interventions to both ERI and pain may be worthwhile
      to prevent a vicious cycle.

PMID- 29596158
TI  - Spinal manipulation and exercise for low back pain in adolescents: a randomized
      trial.
AB  - Low back pain (LBP) is common in adolescence, but there is a paucity of high
      quality research to inform care. We conducted a multicenter randomized trial
      comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise
      therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years
      with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks.
      Secondary outcomes included disability, quality of life, medication use, patient-
      and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using
      longitudinal linear mixed effect models. An omnibus test assessing differences in
      individual outcomes over the entire year controlled for multiplicity. Of the 185
      enrolled patients, 179 (97%) provided data at 12 weeks and 174 (94%) at 26 and 52
      weeks. Adding SMT to ET resulted in a larger reduction in LBP severity over the
      course of 1 year (P = 0.007). The group difference in LBP severity (0-10 scale)
      was small at the end of treatment (mean difference = 0.5; P = 0.08) but was
      larger at weeks 26 (mean difference = 1.1; P = 0.001) and 52 (mean difference =
      0.8; P = 0.009). At 26 weeks, SMT with ET performed better than ET alone for
      disability (P = 0.04) and improvement (P = 0.02). The SMT with ET group reported
      significantly greater satisfaction with care at all time points (P <= 0.02).
      There were no serious treatment-related adverse events. For adolescents with
      chronic LBP, spinal manipulation combined with exercise was more effective than
      exercise alone over a 1-year period, with the largest differences occurring at 6
      months. These findings warrant replication and evaluation of cost effectiveness.

PMID- 29596160
TI  - Introduction.

PMID- 29596161
TI  - Chapter 1. The Historical Roots of Paediatric Gastroenterology, Hepatology, and
      Nutrition.
AB  - The last 50 years have seen the establishment of paediatric gastroenterology,
      hepatology, and nutrition (PGHAN) as a well-recognised and thriving clinical
      specialty throughout most of Europe, and further afield. This has happened, in
      part, through the existence of the European Society for Paediatric
      Gastroenterology and Nutrition (ESPGHAN) as a forum for those interested in this
      branch of children's medicine. To illustrate the pan-European roots of PGHAN,
      some key scientific and medical events, discoveries, and inventions relevant to 3
      common clinical problems-diarrhoea, jaundice, and infant-feeding-have been chosen
      to survey the historical development of the ways in which each was understood and
      treated within the changing thinking and practice of past times. Together they
      are used to trace the prehistory of ESPGHAN and provide a background against
      which to explain the genesis of the Society and how its spheres of clinical and
      scientific interest came to be defined.

PMID- 29596162
TI  - Chapter 2. ESPGHAN: 50 Years Memories-The Early Years.
AB  - Thirty-six founding members from Europe were present in 1968, when the European
      Society of Paediatric Gastroenterology (ESGA) had its first meeting in Paris. The
      aim was to create a forum for presentations and discussions of research
      activities in paediatric gastroenterology in Europe. At the second meeting of
      ESGA 1969 in Interlaken, an important landmark was set for all
      gastroenterologists in the world. In this conference, the first ever criteria for
      "the Diagnosis of Coeliac Disease" (CD) were established. In 1990, the revised
      criteria for the diagnosis of CD were published. After the introduction of new
      noninvasive techniques, like tissue transglutaminase 2-antibodies and the
      HLADQ2/HLADQ8 determinations in blood, "new" criteria for the diagnosis of CD
      were published in 2012 by the European society of Paediatric Gastroenterology,
      Hepatology and Nutrition (ESPGHAN). Close collaboration of ESPGHAN and the North
      American Society of Paediatric Gastroenterology, Hepatology and Nutrition led to
      mutual meetings. The first combined meeting was 1978 in Paris, followed by
      meetings in New York, Amsterdam, Houston, and last in Toulouse. The first World
      Congress of Paediatric Gastroenterology took place in Boston 2000 followed by
      congresses in Paris, Iguazu, Taipeh, and Toronto. The creation of specialised
      committees (Nutrition Committees, GI-Committee, and Hepatology-Committee) enabled
      the society to elaborate numerous guidelines for standards in the diagnosis and
      treatment of diseases within the subspecialties. The Journal of Paediatric
      Gastroenterology and Nutrition, as organ of ESPGHAN and the North American
      Society of Paediatric Gastroenterology, Hepatology and Nutrition since 1991,
      serves as the voice for these worldwide accepted guidelines. Growing educational
      activities with summer schools, the Young Investigator Forum and the creation of
      working groups have distributed our current knowledge among the younger
      generation and led to fruitful reports, guidelines, and syllabus. In 1992,
      ESPGHAN was 1 of the founding 7 members of the United European Gastroenterology
      Federation (UEGF), which developed into a successful organisation for
      gastroenterology in Europe. This year we celebrate the 50th anniversary of
      ESPGHAN at our annual Meeting in Geneva.

PMID- 29596163
TI  - Chapter 3. The European Society for Paediatric Gastroenterology, Hepatology and
      Nutrition in Recent Years.
AB  - The European Society for Paediatric Gastroenterology, Hepatology and Nutrition
      has experienced an amazing development in the 50 years of its existence. It grew
      from a small group of 36 friends who held an informal meeting with some 20 oral
      presentations to share and discuss their clinical and research work, to a large,
      multiprofessional society that sets widely recognized standards for clinical care
      and policy and hosts the world's largest congress of Paediatric Gastroenterology,
      Hepatology and Nutrition with more than 4500 delegates from 100 countries.
      However, the Society's mission has remained the same: to promote the health of
      children with special attention to the gastrointestinal tract, liver, and
      nutritional status, through knowledge creation, the dissemination of science
      based information, the promotion of best practice in the delivery of care and the
      provision of high-quality education. The European Society for Paediatric
      Gastroenterology Hepatology and Nutrition's success is based on the enthusiasm
      and engagement of its membership that contribute extensive volunteer work to
      support child health, while maintaining a positive spirit of collaboration and
      friendship, which characterises this Society. This article aims at describing
      recent developments and the current situation of the European Society for
      Paediatric Gastroenterology Hepatology and Nutrition.

PMID- 29596164
TI  - Chapter 4. The Relationship Between the European and North American Societies for
      Pediatric Gastroenterology, Hepatology and Nutrition.
AB  - This chapter is based on the memories of those who shaped the relationship
      between the European and the North American Societies for Pediatric
      Gastroenterology, Hepatology and Nutrition. The first joint meeting of the 2
      Societies took place in Paris in 1978, followed by 1 in New York in 1985, 1 in
      Amsterdam in 1990, 1 in Houston in 1994, and the last one in Toulouse in 1998.
      The formation of the Federation of the International Societies for Pediatric
      Gastroenterology, Hepatology and Nutrition (FISPGHAN) preceded the First World
      Congress of all Societies, which took place in Boston in 2000. The success of
      this meeting was followed by world congresses in Paris in 2004, Iguassu in 2008,
      Taiwan in 2012, and Montreal in 2016. NASPGHAN and ESPGHAN jointly took on the
      direction of the Journal of Pediatric Gastroenterology and Nutrition in 1991.
      Communication between the 2 Societies is extremely active, with members
      participating in many joint projects.

PMID- 29596166
TI  - Chapter 5.0. 50 Years of Paediatric Gastroenterology.

PMID- 29596165
TI  - Chapter 5. Fifty Years of Paediatric Gastroenterology.

PMID- 29596168
TI  - Chapter 5.1.2. Infectious Diarrhoea.

PMID- 29596167
TI  - Chapter 5.1.1. Coeliac Disease.

PMID- 29596169
TI  - Chapter 5.1.3. Forty Years of Helicobacter Pylori in ESPGHAN.

PMID- 29596170
TI  - Chapter 5.1.4. Paediatric Immune-related Enteropathies.

PMID- 29596171
TI  - Chapter 5.2.1. Short Bowel Syndrome: Half a Century of Progress.

PMID- 29596172
TI  - Chapter 5.2.2. From the Syndrome of Intractable Diarrhoea of Infancy to Molecular
      Analysis and Cell Biology: 50 Years of Evolution.

PMID- 29596173
TI  - Chapter 5.2.3. Parenteral Nutrition and Home Parenteral Nutrition Changed the
      Face of Paediatric Gastroenterology.

PMID- 29596174
TI  - Chapter 5.2.4. Intestinal Transplantation: On a Long and Uneven Road From the
      Past to the Future.

PMID- 29596175
TI  - Chapter 5.3.1. ESPGHAN History of Gastrointestinal Paediatric Endoscopy.

PMID- 29596176
TI  - Chapter 5.3.2. Some Things Have Moved in the World of Motility.

PMID- 29596177
TI  - Chapter 5.3.3. The Story of Gastro-oesophageal Reflux That Became a Disease.

PMID- 29596178
TI  - Chapter 5.4.1. Acute Diarrhoea.

PMID- 29596179
TI  - Chapter 5.4.2. ESPGHAN Made the Gastrointestinal Microbiota Grow.

PMID- 29596180
TI  - Chapter 6. ESPGHAN's Contributions to Paediatric Hepatology.

PMID- 29596181
TI  - Chapter 6.0. History of Paediatric Hepatology in ESPGHAN.
AB  - Hepatology played an important role in ESPGAN from the beginning. In 1989, the
      Hepatology Committee was started. In the early 1990s H for hepatology was
      included in ESPGHAN. Hepatology Summer schools were held from 1995 and later
      monothematic conferences met the needs of many young ESPGHAN members. The role of
      ESPGHAN members in the progress of diagnostic and therapeutic measures in
      hepatitis B and C will be elucidated (Chapter 6.1) as well as the role of other
      ESPGHAN members in the understanding of immunological hepatic disorders of
      childhood (Chapter 6.2). During childhood, many metabolic hepatic disorders
      threaten the life and health of children making orchestrated measures in
      diagnostic and therapeutic efforts necessary (Chapter 6.3). The pathophysiology
      of cholestasis was cleared by the detection of bile salt transporters, which were
      identified by ESPGHAN members in the Netherlands, France, United Kingdom and
      Germany (Chapter 6.4). Finally liver transplantation for acute fulminant and
      chronic end stage liver disease was established as a meanwhile standard treatment
      option (Chapter 6.5). Immunosupression in liver transplantation was improved and
      standardized through the cooperation of many ESPGHAN member driven studies
      (Chapter 6.6).

PMID- 29596182
TI  - Chapter 6.1. Pediatric Chronic Hepatitis B and C: 30 Years of ESPGHAN Clinical
      Research and Recommendations.
AB  - The expression of hepatitis B and C virus infections in children differs from
      that in adults and requires specific paediatric expertise. The European Society
      of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has been a
      pioneer in this field, having stressed the need for straightforward
      recommendations since the mid-1980s. Following much observation, surveillance,
      and research, a panel of ESPGHAN experts was able to develop such recommendations
      on hepatitis B infection in children in 2009, which was then followed in June
      2013 by proper guidelines. In the field of Chronic Hepatitis C, in 2011 ESPGHAN
      experts published also the Guidance for Clinical Trials for Children and
      Adolescents, and approved in 2012 the NASPGHAN guidelines for treatment. The
      ESPGHAN Society is to be commended for its pioneering work in furthering our
      understanding of chronic hepatitis B and C disease presentations in infants,
      children, and adolescents.

PMID- 29596183
TI  - Chapter 6.2. Immune Function-related Liver Disease and ESPGHAN's Contribution to
      the Advancement of Science in the Last 3 Decades.

PMID- 29596184
TI  - Chapter 6.3. Studies on Hepatic Metabolic Disorders Driven by ESPGHAN Members:
      The Case of Alpha1-Antitrypsin Deficiency, Cystic Fibrosis, and Urea Cycle
      Defects.

PMID- 29596185
TI  - Chapter 6.4. Diagnostic Progress in Cholestasis.

PMID- 29596186
TI  - Chapter 6.5. Paediatric Liver Transplantation.

PMID- 29596187
TI  - Chapter 6.6. The Role of ESPGHAN in Developing Effective Immunosuppression
      Following Paediatric Liver Transplantation.

PMID- 29596188
TI  - Chapter 7. The Contributions of the ESPGHAN Committees on Nutrition to Paediatric
      Nutrition.
AB  - The first Committee on Nutrition (CoN) was founded in 1974. Two years later
      nutrition (N) was added to the society's name, which then became ESPGAN. The
      Committee systematised compositional and quality criteria for breast milk
      substitutes and food for special medical purposes, the first of many examples on
      how recommendations and comments published by the Committees on Nutrition (CsoN)
      were adopted by the European Economic Community, later the European Union and
      also influenced the World Health Organization/Food and Agriculture Organization
      of the United Nations Codex standards. A second CoN focusing on preterm infants
      was established in 1979 and its recommendations on nutrition of these infants
      were widely implemented. The third and standing CoN, established 1986, started to
      organise high-quality symposia at the annual meetings appreciating the need to
      enhance the expertise in nutritional research. From 1991 the CoN has organised
      Summer Schools in paediatric nutrition for young colleagues further emphasising
      its educational interest and more recently an annual, more specialised Nutrition
      Masterclass. Successively the interest of the CoN has expanded to other areas,
      such as highlighting dilemmas and uncertainties in the field of nutrition
      including the design, choice of outcomes and statistical analysis of trials in
      infant nutrition. The work of the CsoN have had great impact on paediatric
      nutrition and the committee will continue its important role by writing
      commentaries and systematic reviews and revising guidelines when required to
      inform and stimulate discussion among colleagues as well as stimulate training in
      paediatric nutrition by organising workshops and scientific meetings, training
      courses, and other approaches, and by interaction with other expert groups.

PMID- 29596189
TI  - Chapter 8. 50 Years of the European Society for Paediatric Gastroenterology,
      Hepatology and Nutrition (ESPGHAN): Captivating Witness Reports of a Success
      Story.
AB  - Since the conception of an idea of a few paediatric gastroenterologists in Europe
      to create a society for Paediatric Gastroenterology in 1967, and its foundation
      in 1968, half a century has passed. The European Society for Paediatric
      Gastroenterology, Hepatology and Nutrition (ESPGHAN) now celebrates its 50th
      anniversary and its utmost success in combining clinical and scientific expertise
      in the fields of paediatric gastroenterology, haepatology, and nutrition. To
      describe this success story 14 of the still living presidents of ESPGHAN recount
      their impressions of the steady growth of ESPGHAN with all the historical facets
      from their own points of view. This historical view of ESPGHAN over the last 5
      decades provides personal accounts of the development of all activities and
      creations of this great European Society. The Society started as a small family
      of experts in the field into a global working open society involved in a large
      variety of activities within the subspecialties, becoming a leading organisation
      in Europe and beyond. This unique view gives also a wonderful insight into the
      famous clinicians and researchers from all over Europe who have helped in the
      growth and development of ESPGHAN. By describing all these activities and
      collaborations it becomes clear that this astonishing pan-European enterprise was
      achieved by people who put considerable effort and time into the development of
      this society. Their statements serve as a historical source and reference for
      future evaluation of the first 50 years of ESPGHAN. In depicting different time
      episodes, and by assembling all the historical pieces of a puzzle together, the
      statements help to illustrate how a highly structured society such as ESPGHAN has
      evolved over the last 50 years, for what it stands for today and what is to be
      expected in the future.

PMID- 29596190
TI  - Chapter 9. Words From Partner Societies.
AB  - On the occasion of the 50th anniversary of the European Society of Paediatric
      Gastroenterology, Hepatology and Nutrition (ESPGHAN), its close partner
      associations submitted comments and felicitations which are presented here. These
      include words from the Latin American (LASPGHAN), North American (NASPGHAN) and
      Panarabian Societies (PASPGHAN) and the Commonwealth Association (CAPGHAN) of
      Paediatric Gastroenterology, Hepatology and Nutrition, the Federation of
      International Societies of Paediatric Gastroenterology, Hepatology and Nutrition
      (FISPGHAN), the European Academy of Pediatrics (EAP), the European Pediatric
      Association/Union of National Pediatric Societies (EPA-UNEPSA), the International
      Pediatric Association (IPA), the European Crohn's and Colitis Organisation
      (ECCO), European Society for Clinical Nutrition and Metabolism (ESPEN) , the
      Federation of European Nutrition Societies (FENS), and United European
      Gastroenterology (UEG).

PMID- 29596191
TI  - A 20-Year Experience with 202 Segmental Mandibulectomy Defects: A Defect
      Classification System, Algorithm for Flap Selection, and Surgical Outcomes.
AB  - BACKGROUND: This study establishes a novel and broadly applicable defect
      classification system and flap selection algorithm for segmental mandibulectomy
      defects that emphasize the importance of the soft-tissue deficit, in addition to
      that of the bony defect. METHODS: Between 1992 and 2011, 202 patients with
      mandibulectomy defects underwent immediate reconstruction performed by a single
      surgeon. Details of the bony and soft-tissue defects, recommendations for the
      most appropriate reconstruction for each clinical scenario, and surgical outcomes
      are presented. RESULTS: A total of 211 flaps were performed in 202 patients.
      Forty-one (19 percent) were nonosseous only, and 170 (81 percent) were osseous
      containing. The majority of osseous flaps were fibula osseous or osteocutaneous
      flaps (91 percent), and the majority of nonosseous flaps were vertical rectus
      abdominis myocutaneous flaps (68 percent). Flap selection was influenced by the
      number of soft-tissue zones resected; defects of one soft-tissue zone or less
      were predominantly reconstructed with an osseous flap, whereas defects that
      involved four or more zones underwent reconstruction with only a soft-tissue flap
      in 55 percent of cases. CONCLUSIONS: The algorithm for reconstruction of the
      mandibulectomy defect must include both nonosseous and osseous flaps based on
      defect size, location, and number of soft-tissue zones involved. As the extent of
      the soft-tissue defect increases, nonosseous flaps are preferred because of
      greater reliability of the skin island. The surgical outcomes associated with
      this algorithm are similar to or better than what is published in the literature.
      This series represents the largest reported single-surgeon experience with
      mandibulectomy defect reconstruction.

PMID- 29596192
TI  - Soft-Tissue Reconstruction of the Complicated Knee Arthroplasty: Principles and
      Predictors of Salvage.
AB  - BACKGROUND: Total knee arthroplasty is a common orthopedic procedure in the
      United States and complications can be devastating. Soft-tissue compromise or
      joint infection may cause failure of prosthesis requiring knee fusion or
      amputation. The role of a plastic surgeon in total knee arthroplasty is critical
      for cases requiring optimization of the soft-tissue envelope. The purpose of this
      study was to elucidate factors associated with total knee arthroplasty salvage
      following complications and clarify principles of reconstruction to optimize
      outcomes. METHODS: A retrospective review of patients requiring soft-tissue
      reconstruction performed by the senior author after total knee arthroplasty over
      8 years was completed. Logistic regression and Fisher's exact tests determined
      factors associated with the primary outcome, prosthesis salvage versus knee
      fusion or amputation. RESULTS: Seventy-three knees in 71 patients required soft
      tissue reconstruction (mean follow-up, 1.8 years), with a salvage rate of 61.1
      percent, mostly using medial gastrocnemius flaps. Patients referred to our
      institution with complicated periprosthetic wounds were significantly more likely
      to lose their knee prosthesis than patients treated only within our system.
      Patients with multiple prior knee operations before definitive soft-tissue
      reconstruction had significantly decreased rates of prosthesis salvage and an
      increased risk of amputation. Knee salvage significantly decreased with positive
      joint cultures (Gram-negative greater than Gram-positive organisms) and
      particularly at the time of definitive reconstruction, which also trended toward
      an increased risk of amputation. CONCLUSIONS: In revision total knee
      arthroplasty, prompt soft-tissue reconstruction improves the likelihood of
      success, and protracted surgical courses and contamination increase failure and
      amputations. The authors show a benefit to involving plastic surgeons early in
      the course of total knee arthroplasty complications to optimize genicular soft
      tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29596193
TI  - Skin Rejuvenation through HIF-1alpha Modulation.
AB  - The constant intrinsic and extrinsic stress the skin is exposed to leads to
      significant impairments of the regenerative capacity of aging skin. Current skin
      rejuvenation approaches lack the ability to holistically support the biological
      processes that exhaust during aging skin degeneration, such as collagen
      production, cell migration and proliferation, and new vessel formation. Similar
      to chronic wounds, aged skin is characterized by dysfunction of key cellular
      regulatory pathways impairing regeneration. Recent evidence suggests that the
      same mechanisms hindering a physiologic healing response in chronic wounds are
      the basis of impaired tissue homeostasis in aged skin. Dysfunction of a main
      response-to-injury pathway, the hypoxia-inducible factor (HIF)-1alpha regulatory
      pathway, has been identified as pivotal both in chronic wounds and in aging skin
      degeneration. HIF-1alpha signaling is significantly involved in tissue
      homeostasis and neovascularization, resulting in the production of new collagen,
      elastin, and nourishing blood vessels. Modulating the functionality of this
      pathway has been demonstrated to significantly enhance tissue regeneration. In
      this review, we present an overview of the regenerative effects linked to the up
      regulation of HIF-1alpha functionality, potentially resulting in skin
      rejuvenation on both the cellular level and the tissue level.

PMID- 29596194
TI  - Tumor-to-Nipple Distance as a Predictor of Nipple Involvement: Expanding the
      Inclusion Criteria for Nipple-Sparing Mastectomy.

PMID- 29596195
TI  - Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of
      the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to
      Success?

PMID- 29596196
TI  - Reply: How to Preshape the Breast for a Successful Nipple-Sparing Mastectomy and
      Direct-to-Implant Breast Reconstruction in the Challenging Breast.

PMID- 29596197
TI  - Quilting Sutures after Latissimus Dorsi Breast Reconstruction in Breast Cancer
      Patients Might Lead to Reduced Risk of Developing Arm Lymphedema by Reducing
      Seroma Risk.

PMID- 29596198
TI  - Optimizing Aesthetics with Prosthetic Prepectoral Breast Reconstruction.

PMID- 29596199
TI  - Reply: Optimizing Aesthetics with Prosthetic Prepectoral Breast Reconstruction.

PMID- 29596200
TI  - Indications for Prepectoral Breast Reconstruction.

PMID- 29596201
TI  - Reply: Indications for Prepectoral Breast Reconstruction.

PMID- 29596202
TI  - Selective Serotonin Reuptake Inhibitor-Induced Hyponatremia and the Plastic
      Surgery Patient.

PMID- 29596203
TI  - Validation of the Clinician-Graded Electronic Facial Paralysis Assessment.

PMID- 29596204
TI  - Reply: Validation of the Clinician-Graded Electronic Facial Paralysis Assessment.

PMID- 29596205
TI  - Do Our Large Surgical Databases Need a Transition?

PMID- 29596206
TI  - Constrictive Bronchiolitis in Patients With Primary Sjogren Syndrome.
AB  - OBJECTIVE: Constrictive bronchiolitis (CB) is a poorly understood pulmonary
      manifestation of primary Sjogren syndrome (pSS). We aimed to clarify the
      presenting clinicoradiologic features and clinical course of pSS-associated CB
      through a retrospective cohort study. METHODS: We retrospectively identified 11
      patients with pSS and CB (defined by mosaic pattern with air trapping on computed
      tomography) encountered at our institution over 9 years from 2007 to 2015.
      Presenting clinical features, laboratory results, radiologic findings, and
      clinical course were analyzed. RESULTS: Our patients were mostly women (91%),
      with a median age 53 years (range, 31-76 years) at the time of pulmonary symptom
      (dyspnea or cough) onset. Most (64%) were nonsmokers. Average interval between
      diagnosis of pSS and the onset of pulmonary symptoms was 4.4 years; in 4 patients
      (36%), CB was the presenting manifestation of pSS. Chest radiographs were normal
      (67%) or demonstrated hyperinflation (33%). Pulmonary function testing
      demonstrated airflow obstruction in 7 patients (63%), and 2 patients (18%) had an
      isolated reduction in diffusing capacity, whereas the remaining 2 patients
      manifested mixed physiology or normal results. Surgical lung biopsy was performed
      in 2 patients and confirmed the diagnosis of CB in both. Treatment was variable
      among our patients included glucocorticoids, hydroxychloroquine, mycophenolate
      mofetil, and cyclophosphamide. Among 6 patients with follow-up computed
      tomography and pulmonary function, the results remained stable or worsened.
      CONCLUSIONS: Constrictive bronchiolitis is a rare extraglandular manifestation
      and can sometimes be the presenting manifestation of pSS. This pulmonary
      manifestation is associated with an indolent clinical course and does not respond
      well to immunosuppressive therapy.

PMID- 29596207
TI  - Use of Abatacept in Chilean Patients With Long-standing Severe Rheumatoid
      Arthritis Without Previous Use of Biologics.

PMID- 29596208
TI  - A Consensus Position Paper From REAL-PANLAR Group About the Methodological
      Approach for the Accreditation Process of Centers of Excellence in Rheumatoid
      Arthritis in Latin America.
AB  - BACKGROUND: By 2015, the World Health Organization reported that 1% of the world
      population suffered from rheumatoid arthritis (RA) and in Latin America (LATAM)
      between 0.5% and 1%. Previously, in May 2014, a consensus meeting was held in
      Barranquilla, Colombia, where the Project for Implementation and Accreditation of
      Centers of Excellence (CoE) in RA in LATAM was established, which then became an
      official special group of the Pan American League of Associations for
      Rheumatology (PANLAR). OBJECTIVE: The aim of this study was to define the
      methodological approach for the accreditation process of CoE in RA in LATAM.
      METHODS: A meeting was held in April 2015 with participation of the members of
      the REAL-PANLAR Steering Committee, and representatives of several LATAM
      countries, with the support of 2 experts in accreditation processes and models in
      Colombia. Then, in November 2015 in San Francisco and in November 2016 in
      Washington, the REAL-PANLAR Steering Committee met to discuss some final aspects
      of the project. RESULTS: The following steps for accreditation were defined:
      application for accreditation, issuance of the concept of assessment of the
      entity, accreditation decision, and monitoring accreditation. CONCLUSIONS: This
      is the second REAL-PANLAR consensus paper with the purpose to define the
      parameters for the accreditation process for future CoE in RA in LATAM.

PMID- 29596209
TI  - The Bath Ankylosing Spondylitis Metrology Index Varies Significantly During the
      Daytime.

PMID- 29596211
TI  - From Gutenberg to Facebook.

PMID- 29596210
TI  - Sacroiliitis in Children With Familial Mediterranean Fever.
AB  - BACKGROUND/OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal
      recessive disease, characterized by recurrent, self-limited attacks of fever with
      serositis. Various diseases were reported to be associated with FMF. The aim of
      this study was to investigate the frequency and characteristics of sacroiliitis
      in children with FMF. METHODS: Files of FMF patients who had been seen in 2
      reference hospitals in Ankara were retrospectively evaluated. Patients with FMF
      and concomitant sacroiliitis were included to the study. All patients had
      magnetic resonance imaging evidence of sacroiliitis. RESULTS: Among 650 FMF
      patients, 17 (11 females, 6 males; mean age, 13.32 +/- 4.24 years) (2.6%) of them
      were found to have sacroiliitis. Familial Mediterranean fever diagnosis was done
      prior to sacroiliitis diagnosis in 11 patients (65%) and concurrently or
      afterward in 6 patients (35%). Ten patients had isolated sacroiliitis, and 7 had
      associated diseases (5 enthesitis-related arthritis, 1 psoriatic arthritis, and 1
      ulcerative colitis). Arthritis (59%), arthralgia (77%), leg pain (71%), heel pain
      (41%), and enthesitis (29%) were common complaints. Sacroiliac tenderness was
      detected in 77%, and M694V mutation in almost 90% of the patients. All patients
      received colchicine therapy. Additionally, 14 of them were treated with
      nonsteroidal anti-inflammatory drugs, 10 were on sulfasalazine treatment, and 7
      of them were on biological agents. CONCLUSIONS: Sacroiliitis can be seen in
      patients with FMF during childhood, and M694V mutation seems to be a
      susceptibility factor for its development. Inflammatory low-back pain and leg and
      heel pain could suggest sacroiliitis.

PMID- 29596212
TI  - Perioperative Nutritional Optimization in Spine Surgery.
AB  - Nutritional optimization in patients undergoing spine surgery is important as
      improved surgical outcomes and decreased rates of complications have been noted
      in optimized patients. With the increasingly high numbers of elderly patient and
      patients with metabolic comorbidities undergoing spine procedures, perioperative
      nutritional status should be enhanced for the best possible surgical outcomes.
      Methods of optimization include preoperative screening with Nutritional Risk
      Score or other scoring systems, looking for changes in body mass index, detecting
      sarcopenia, and screening for metabolic abnormalities. Assessment of blood
      glucose, electrolytes, cholesterol, vitamin levels, visceral proteins, and lean
      body mass must be done preoperatively and close monitoring should be continued
      postoperatively. Albumin helps to determine the health status of patients before
      surgery and prealbumin as a predictor of surgical outcomes is being investigated.
      Malnourished patients should be given balanced diets replenishing key nutrient
      deficits, glucose should be maintained with sliding scale insulin or continuous
      infusions and immunonutrition may be implemented. Postoperatively, patients
      should initiate a diet as soon as possible to decrease overall length of stay and
      complication rates, facilitating return to normal activities.

PMID- 29596213
TI  - A Prospective Single-blind Randomized Controlled Trial of Chewing Gum on Bowel
      Function Recovery After Posterior Spinal Fusion Surgery for Adolescent Idiopathic
      Scoliosis.
AB  - PURPOSE: To evaluate the effectiveness of chewing gum on promoting bowel function
      recovery in adolescent idiopathic scoliosis patients undergoing surgical
      correction. MATERIALS AND METHODS: Adolescent idiopathic scoliosis patients
      scheduled for posterior spinal fusion surgery at our institution were randomized
      to either group 1 (chewing gum) or group 2 (control). The primary endpoints were
      time to flatus, time to bowel movement, length of hospital stay, and time to
      liquid or solid. The secondary endpoints were postoperative opioid consumption,
      incidence of complications, pain scores, and nausea scores. In addition, a meta
      analysis of available data from the literature was performed identifying 2
      studies with quantitative data on the efficacy of gum chewing after scoliosis
      correction surgery. RESULTS: In total, 125 patients (63 gum; 62 control) were
      included in our analysis after randomization. There was no significant difference
      in time to first flatus (P=0.087), time to bowel movement (P=0.307), time to
      liquid or solid, length of postoperative hospital stay (P=0.954), postoperative
      complications, opioid consumption, and postoperative nausea scores between the 2
      groups. The postoperative pain scores on postoperative day 1 were significantly
      lower (P=0.027). There was a significant decrease in the time to the first flatus
      for patients having selective thoracic fusion in both groups than those having
      fusion to lumbar spine. Meta-analysis also indicated there was no significant
      difference in outcomes of bowel function between the 2 groups. CONCLUSIONS: Our
      institutional data and meta-analysis collaboratively suggested that chewing gum
      did not hasten the return of bowel function.

PMID- 29596214
TI  - Natural History and Prognostic Factors of Cholangiocarcinoma With Spinal
      Metastasis: A 10-Year Single Center Study.
AB  - STUDY DESIGN: This is a retrospective analysis. OBJECTIVE: The aim of this study
      was to determine the epidemiology, survival, and prognostic factors for
      cholangiocarcinoma (CCA) with spinal metastasis. SUMMARY OF BACKGROUND DATA: CCA
      is an epithelial cell malignancy of the bile duct, and a frequent site for its
      metastasis is the spine. Many areas of Asia are endemic for CCAs. To date, there
      is limited data on the epidemiology, natural history, and prognostic factors of
      CCA with spinal metastasis, which is crucial for better management and treatment
      of the disease. MATERIALS AND METHODS: Patients diagnosed with CCA were recruited
      to our study, in order to identify cases with spinal metastasis. The survival
      rate was estimated by the Kaplan-Meier method. The univariate and multivariate
      analyses of tumor-specific and spinal metastatic factors were performed to
      identify the independent factors that affect survival. RESULTS: From 2006 to
      2015, 4585 CCA patients were identified and 182 of these patients had spinal
      metastasis. The overall median survival of patients with spinal metastasis was 88
      days. Serum carcinoembryonic antigen <5 ng/mL, carbohydrate antigen 19-9 <39
      U/mL, albumin >=3.5 g/L, and Frankel score D-E were found to be independent
      factors that resulted in better survival in a multivariate Cox regression
      analysis. CCA resection or spinal surgery did not prolong the survival of
      patients with spinal metastasis. CONCLUSION: Spinal surgery should be considered
      for CCA patients with spinal metastasis, who have a favorable prognosis, and are
      likely to live long enough to benefit from surgery. The aim is to palliate the
      symptoms and not as much to improve the survival.

PMID- 29596215
TI  - Incidence and Risk Factors for Proximal Junctional Kyphosis: Results of a
      Multicentric Study of Adult Scoliosis.
AB  - STUDY DESIGN: This was a retrospective multicentric study. OBJECTIVE: The
      objective of this study was to determine the different risk factors for
      development of proximal junctional kyphosis (PJK) in patients with adult
      scoliosis. SUMMARY OF BACKGROUND DATA: This study was conducted as the reasons
      for development of PJK in adult scoliosis are still not clear. MATERIALS AND
      METHODS: In total, 314 patients met the inclusion criteria. The main outcome
      measure was the PJK, as described by Glattes and colleagues. Extent of the
      instrumentation, operative time, bleeding, and the use of an osteotomy as well as
      the type of proximal anchorage were collected. Radiologic variables included
      preoperative Cobb angles of the lumbar and the thoracic curvatures, pelvic
      parameters, lumbar lordosis, thoracic kyphosis, and sagittal vertical axis. All
      measures were performed using the KEOPS software. RESULTS: The mean follow-up of
      this series was 2.5 years with a female to male ratio of 6.6/1 and a mean age of
      56.66 years. The incidence of PJK was 25%. Proximal fixation extended to the
      proximal thoracic spine (TS) in 39%, to the middle TS in 39.5% of cases, and to
      the thoracolumbar junction in 20.4%, with a higher incidence of PJK noted in the
      first group. The proximal anchors had no effect on PJK incidence. Age as well as
      body mass index had a positive correlation to the incidence of PJK. The
      association, fusion to sacrum and fusion to the upper TS, is associated with the
      highest incidence of PJK. Preoperative pelvic tilt had a positive correlation
      with PJK occurrence. Finally, revision for PJK occurred in 2.3% of all patients
      and accounted for 15% of revisions. CONCLUSIONS: Increased age, as well as
      increased body mass index, is a risk factor for the development of PJK. The
      proximal extent of the construct is also shown to be a risk factor for PJK, but
      fusion to the sacrum is a risk factor only if fusion extends to the proximal TS.
      Moderate PJK was observed with undercorrection of the sagittal balance and severe
      PJKs with overcorrection of the sagittal balance. LEVEL OF EVIDENCE: Level IV.

PMID- 29596216
TI  - Reduction of Inappropriate Antimicrobial Prescriptions in a Tertiary Neonatal
      Intensive Care Unit Following Antimicrobial Stewardship Care Bundle
      Implementation.
AB  - BACKGROUND: Our objective was to evaluate the appropriateness of antibiotic
      prescriptions in the neonatal intensive care unit (NICU) using standardised
      criteria and determine the effects of an antimicrobial stewardship programme
      (ASP) on patterns of antibiotic usage. METHODS: A retrospective audit of
      antibiotic use from July 2010-June 2013 was conducted, focusing on prescriptions
      of vancomycin, cefotaxime, meropenem and linezolid for >3 calendar days. We
      evaluated the appropriateness of each course of antibiotic treatment based on the
      Centers for Disease Control and Prevention (CDC) 12-Step Guidelines to Prevent
      Antimicrobial Resistance (Steps 4, 6 and 9). An ASP was introduced in August
      2014, and the same audit criteria were applied to review antimicrobial use in the
      subsequent 12 months. RESULTS: In the pre-ASP era, 26.3%, 12.1%, 11.4% and 0% of
      meropenem, cefotaxime, vancomycin and linezolid courses, respectively, were
      inappropriate. The most common instance of inappropriate utilisation included
      failure to use narrower-spectrum antimicrobials when appropriate. After the
      introduction of ASP programme, 22.2%, 7.5%, 5.4% and 0% of meropenem, cefotaxime,
      vancomycin and linezolid courses, respectively, were inappropriate. The numbers
      of inappropriate antibiotic-days/1000 days of therapy with meropenem, cefotaxime
      and vancomycin changed from 1.89 to 1.96 (rate ratio RR=1.04 [0.70,1.52]), 3.56
      to 1.73 (RR=0.49[0.33,0.71]) and 2.70 to 1.01 (RR=0.37[0.22,0.60]), respectively.
      In sub-group analysis, very-low-birth-weight infants (VLBW, birth
      weight<1500grams) showed no improvement in the rates of inappropriate antibiotic
      prescriptions. CONCLUSION: In this study, we found that ASP initiatives can be
      applied in neonatal populations to reduce inappropriate antimicrobial
      prescriptions, though a different approach may be needed among VLBW infants.

PMID- 29596218
TI  - Dietary Supplementation with Medium-Chain Triglycerides Reduces Candida
      Gastrointestinal Colonization in Preterm Infants.
AB  - BACKGROUND: Candida is an important cause of infections in premature infants.
      Gastrointestinal colonization with Candida is a common site of entry for
      disseminated disease. The objective of this study was to determine whether a
      dietary supplement of medium-chain triglycerides (MCTs) reduces Candida
      colonization in preterm infants. METHODS: Preterm infants with Candida
      colonization (n=12) receiving enteral feedings of either infant formula (n=5) or
      breastmilk (n=7) were randomized to MCT supplementation (n=8) or no
      supplementation (n=4). Daily stool samples were collected to determine fungal
      burden during a 3 week study period. Infants in the MCT group received
      supplementation during 1 week of the study period. The primary outcome was fungal
      burden during the supplementation period as compared to the periods before and
      after supplementation. RESULTS: Supplementation of MCT led to a marked increase
      in MCT intake relative to unsupplemented breast milk or formula as measured by
      capric acid content. In the treatment group, there was a significant reduction in
      fungal burden during the supplementation period as compared to the period before
      supplementation (RR = 0.15, p = 0.02), with a significant increase after
      supplementation was stopped (RR = 61, p < 0.001). Fungal burden in the control
      group did not show similar changes. CONCLUSIONS: Dietary supplementation with MCT
      may be an effective method to reduce Candida colonization in preterm infants.

PMID- 29596217
TI  - Financial Incentives for Pediatric HIV Testing in Kenya.
AB  - The acceptability of financial incentives for pediatric HIV testing was evaluated
      in Kenya. Sixty HIV-positive women with children of unknown status were
      randomized to receive $5, $10 or $15 conditional upon HIV testing. Forty-four
      (73%) completed child testing, with similar rates across arms. Uptake was
      significantly higher than a cohort with similar procedures but no incentives (73%
      vs. 14%, P < 0.001).

PMID- 29596219
TI  - Efficacy and Safety of Echinocandins for the Treatment of Invasive Candidiasis in
      Children: A Meta-Analysis.
AB  - BACKGROUND: Echinocandins are recommended for the treatment of suspected or
      confirmed invasive candidiasis (IC) in adults. Less is known about the use of
      echinocandins for the management of IC in children. The aim of this study was to
      investigate the overall efficacy and safety of echinocandin class in neonatal and
      pediatric patients with IC. METHODS: PubMed, Cochrane Central, Scopus and
      Clinical trial registries were searched up to July 27, 2017. Eligible studies
      were randomized trials (RCTs) that evaluated the efficacy and safety of any
      echinocandin versus agents of other antifungal classes for the treatment of IC in
      pediatric patients. The primary outcome was treatment success with resolution of
      symptoms and signs, and absence of IC. In the meta-analysis a random effects
      model was used, and the odds ratio (OR) and 95% confidence intervals (CI) were
      calculated. RESULTS: Four randomized clinical trials (324 patients), 2 confirmed
      IC (micafungin vs. liposomal amphotericin B and caspofungin vs. liposomal
      amphotericin B) and 2 empirical therapy trials (caspofungin vs. deoxycholate
      amphotericin B and caspofungin vs. liposomal amphotericin B) were included. There
      was no significant difference between echinocandins and comparator in terms of
      treatment success (OR=1.61, 95% CI 0.74-3.50) and incidence of treatment-related
      adverse events (OR=0.70, 95% CI 0.39-1.26). However, fewer children treated with
      echinocandins discontinued treatment due to adverse events than amphotericin B
      formulations (OR=0.26, 95% CI 0.08-0.82, p=0.02). CONCLUSIONS: In the treatment
      of IC in children echinocandins show non-inferior efficacy compared to
      amphotericin B formulations with fewer discontinuations than in comparator arm.

PMID- 29596220
TI  - Fusobacterium necrophorum as an Emerging Pathogen of Acute Mastoiditis.
AB  - BACKGROUND: Recent reports have reported an increase in the incidence of acute
      mastoiditis due to Fusobacterium necrophorum. However, the crude incidence and
      the specific clinical and laboratory characteristics of F.necrophorum mastoiditis
      in children have not been described. Our aim was to describe these features, in
      order to identify high-risk patients. METHODS: The electronic medical records of
      all children with acute mastoiditis at a tertiary medical center between 7/2011
      and 12/2015 were analyzed. Using a stepwise logistic regression to identify
      independent risk factors for F. necrophorum, we formulated a predictive model.
      RESULTS: F. necrophorum was identified in 13% (19/149) of mastoiditis cases with
      an identifiable agent. Its incidence increased 7-fold from 2.8% in 2012 to 20.4%
      in 2015 (p=0.02). F. necrophorum infection had unique clinical, laboratory and
      prognostic features. The vast majority had complications and underwent surgical
      intervention. The predictive model used four parameters to define high-risk
      patients for F. necrophorum infection at admission: females, winter/spring
      season, prior antibiotic treatment and a CRP value>20 mg/dL (area under ROC curve
      0.929). CONCLUSIONS: Clinicians should be aware of the increasing incidence of
      F.necrophorum mastoiditis and consider anaerobic cultures and specific anaerobic
      coverage in high-risk patients.

PMID- 29596221
TI  - Increasing Prevalence of Pediatric Drug-resistant Tuberculosis in Mumbai, India,
      and Its Outcome.
AB  - BACKGROUND: The prevalence and type of Drug resistant tuberculosis (DR-TB) was
      evaluated pre- and post-2013, and outcome was studied. METHODS: Descriptive
      retrospective study. Children were defined as having DR-TB on the basis of
      GeneXpert or line probe assay and/or drug susceptibility testing (DST) of M.
      tuberculosis grown on culture or from contact's DST. RESULTS: The prevalence of
      DR-TB was 110 of 1145 cases (9.6%), which showed an increase, compared with 5.6%
      pre-2010 and 7% in 2010-2013 (P = 0.014408). Twenty-two children (20%) had
      pulmonary-TB and 88 (80%) had extra-pulmonary-TB with disseminated-TB being the
      most common presentation in 31 children (28.18%). Ninety-six children (87.3%)
      were bacteriologically confirmed TB cases, and 14 (12.7%) were clinically
      diagnosed-TB and treated as per contact DST. Eight cases (7.2%) were
      monoresistant, 7 (6.3%) polyresistant, MDR-TB seen in 28 patients (25.45%), 32
      (29.09%) had pre-XDR-TB, 9 (8.18%) had XDR-TB and 12 (10.9%) were rifampicin
      resistant. Ethionamide resistance increased from 26.1% pre-2013 to 60.8% post
      2013 (P = 0.014408) and ofloxacin resistance rose from 30.4% pre-2010, to 47.6%
      in 2010-2013 and 56.9% post-2013 (P = 0.080863). Moxifloxacin resistance showed
      an acute rise from 8.7% pre-2010, to 46% in 2010-2013 and 57% post-2013 (P =
      0.000275). Thirty-three patients (30%) had completed their treatment, 21 (19.09%)
      were lost to follow-up and 56 (50.09%) patients are still on treatment.
      CONCLUSIONS: DR-TB is increasing in Mumbai, India. Based on the DST results,
      individualised therapy would be recommended.

PMID- 29596223
TI  - Syphilis Elimination: Lessons Learned Again.
AB  - It is estimated that approximately 20 million new sexually transmitted infections
      (STIs) occur each year in the United States. The federally funded sexually
      transmitted disease prevention program implemented by Centers for Disease Control
      and Prevention is primarily focused on the prevention and control of the three
      most common bacterial STIs: syphilis, gonorrhea, and chlamydia. A range of
      factors facilitate the transmission and acquisition of STIs, including syphilis.
      In 1999, Centers for Disease Control and Prevention launched the National
      Campaign to Eliminate Syphilis from the United States. The strategies were
      familiar to public health in general and to sexually transmitted disease control
      in particular: (1) enhanced surveillance, (2) expanded clinical and laboratory
      services, ((3) enhanced health promotion, (4) strengthened community involvement
      and partnerships, and (5) rapid outbreak response. This national commitment to
      syphilis elimination was not the first effort, and like others before it too did
      not succeed. However, the lessons learned from this most recent campaign can
      inform the way forward to a more comprehensive approach to the prevention and
      control of STIs and improvement in the nation's health.

PMID- 29596222
TI  - A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With
      Invasive Candidiasis.
AB  - BACKGROUND: Amphotericin B deoxycholate (AmB-D) is standard of care treatment for
      neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum
      fungicidal activity against Candida spp. We compared the efficacy and safety of
      intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA
      in infants >2-120 days of age with proven IC in a phase 3, randomized, double
      blind, multicenter, parallel-group, noninferiority study (NCT00815516). METHODS:
      Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for >=21
      days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last
      study drug dose. MCA population pharmacokinetics included simulated area under
      the curve (AUC) at steady state and maximum plasma concentration after 2-hour
      infusion. AUC pharmacodynamic target exposure was 170 ug.h/mL. RESULTS: Thirty
      infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early
      because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence
      interval (CI): 36%-81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%-93%)
      AmB-D-group infants. The most common treatment-emergent adverse events were
      anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%)
      and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA
      was 399.3 +/- 163.9 ug.h/mL (95% prediction interval: 190.3-742.3 ug/mL); steady
      state and maximum plasma concentration after 2-hour infusion was 31.1 +/- 10.5
      ug/mL (95% prediction interval: 17.0-49.7 ug/mL). MCA exposures were above the
      AUC pharmacodynamic target exposure. CONCLUSIONS: Within the study limitations,
      infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both
      agents were safe and well tolerated.

PMID- 29596224
TI  - CDC Syphilis Summit - Diagnostics and Laboratory Issues.
AB  - Syphilis, caused by the bacterium Treponema pallidum, is on the rise in the
      United States (US) particularly among men who have sex with men (MSM). The
      disease is complex with varied clinical manifestations and challenges remain in
      the laboratory diagnostic setting because T. pallidum is non-cultivable 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
      (P&S) 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- 29596226
TI  - Subsequent HIV Diagnosis Risk After Syphilis in a Southern Black Population.
AB  - BACKGROUND: Southern non-Hispanic black persons are disproportionately
      represented in the HIV epidemic. Those previously diagnosed as having syphilis
      are at significant risk to become HIV infected within 36 months. Effective
      prevention strategies such as preexposure prophylaxis should be offered to those
      at highest risk to maximize prevention efforts. METHODS: HIV-negative persons
      diagnosed as having primary or secondary (P&S) syphilis during 1998-2014 were
      matched with incident HIV cases diagnosed during 1998-2016 in Shelby County
      Tennessee. Person-year HIV incidence rate, Kaplan-Meier survival estimates, and
      Cox proportional regression model analyses were performed to explore predicting
      risk factors and quantifying risk factors associated with HIV-free survival time
      frames. RESULTS: Among 2032 HIV-negative non-Hispanic black Shelby County
      residents diagnosed as having P&S syphilis, 139 (6.8%) were subsequently
      diagnosed as having HIV infection. Men who have sex with men (MSM) experienced
      the highest incidence of HIV diagnosis rate (4.98 per 100 person-years, 95%
      confidence interval, 4.76-5.2). Being male, MSM, younger than 30 years, or
      coinfected with gonorrhea increased risk of HIV acquisition 2.32, 11.80, 1.67,
      and 2.44 times, respectively, compared with being female, heterosexual men, 30+
      years old, or not infected with other sexually transmitted infections.
      CONCLUSIONS: Among our population diagnosed as having P&S syphilis, 1 in 6 MSM
      and 1 in 16 persons coinfected with gonorrhea were subsequently diagnosed as
      having HIV during 36 months of follow-up. These findings have implications for
      HIV screening and recruitment as priority preexposure prophylaxis candidates.

PMID- 29596225
TI  - Use of Oral Fluid With a Rapid Treponemal Test for Syphilis Evaluation.
AB  - We aimed to determine if rapid treponemal tests intended for whole-blood
      specimens could be used to detect treponemal antibody in oral fluid. We found a
      high sensitivity of oral fluid rapid testing, which increased with increasing
      rapid plasma reagin titer, suggesting potential for the development of accurate
      rapid oral syphilis tests.

PMID- 29596227
TI  - The Kids Are Not Alright.
AB  - Several articles highlight the need for more child-friendly policies, programs,
      and practices.

PMID- 29596228
TI  - An Exodus of Bedside Nurses.

PMID- 29596229
TI  - An Exodus of Bedside Nurses.

PMID- 29596230
TI  - An Exodus of Bedside Nurses.

PMID- 29596231
TI  - An Exodus of Bedside Nurses.

PMID- 29596232
TI  - An Exodus of Bedside Nurses.

PMID- 29596233
TI  - An Exodus of Bedside Nurses.

PMID- 29596234
TI  - Short-Term Medical Missions: Toward an Ethical Approach.
AB  - Projects must have clearly stated intentions and sustainability plans.

PMID- 29596235
TI  - HHS Division to Enforce 'Conscience and Religious Freedom'.
AB  - When do a clinician's rights deny those of the patient?

PMID- 29596236
TI  - Mandatory Parental Counseling Reduces Vaccine Exemptions.
AB  - States take steps to increase vaccination rates for entering kindergartners.

PMID- 29596239
TI  - Among Other Industrialized Countries, the United States Has Highest Childhood
      Mortality Rate.
AB  - 'Need to think beyond medical care to address social environment.'

PMID- 29596241
TI  - Duration of Postoperative Opioid Use Predicts Misuse More Than Dosage.
AB  - A recent study found misuse increased by more than 40% with each refill.

PMID- 29596244
TI  - Hysterectomy Associated with Long-Term Health Risks.
AB  - Preserving the ovaries does not seem to be protective.

PMID- 29596245
TI  - The Value of Simulation in Nursing Education.
AB  - This clinical activity is transforming nursing training and practice.

PMID- 29596248
TI  - States Can Now Add Work Requirements for Medicaid Recipients.
AB  - Health advocates fear new hurdles will leave thousands more uninsured.

PMID- 29596249
TI  - New Hypotension Treatment for Septic Shock.

PMID- 29596250
TI  - Major Change in Warning for Asthma Drugs.

PMID- 29596251
TI  - New FDA Web Page on Antimicrobial Resistance.

PMID- 29596252
TI  - New Route for Buprenorphine Administration.

PMID- 29596256
TI  - Retiring with Intention.
AB  - : An increasing number of nurses are approaching retirement age and finding
      themselves faced with numerous challenges and opportunities. Yet many avoid
      thinking about and preparing for this important professional and personal
      transition. Some cannot imagine what they will do when their career ends, whereas
      others do not believe they are financially ready to retire. This article
      discusses strategies to address these and other common concerns and will help
      nurses embrace this new and exciting stage of their lives with deliberation,
      confidence, and financial security.

PMID- 29596257
TI  - The Efficacy of Renin Inhibitors in Primary Hypertension.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

PMID- 29596258
TI  - The Great London Smog of 1952.
AB  - : The Great London Smog of December 1952 lasted five days and killed up to 12,000
      people. The smog developed primarily because of extensive burning of high-sulfur
      coal. The health effects were both immediate and long lasting, with a recent
      study revealing an increased likelihood of childhood asthma development in those
      exposed to the Great Smog while in utero or during their first year of life.
      Subsequent pollution legislation-including the U.S. Clean Air Act and its
      amendments-have demonstrably reduced air pollution and positively impacted health
      outcomes. With poor air quality events like the Great Smog continuing to occur
      today, nurses need to be aware of the impact such environmental disasters can
      have on human health.

PMID- 29596259
TI  - Ostomy Care at Home.
AB  - : This article is part of a series, Supporting Family Caregivers: No Longer Home
      Alone, published in collaboration with the AARP Public Policy Institute. Results
      of focus groups, conducted as part of the AARP Public Policy Institute's No
      Longer Home Alone video project, supported evidence that family caregivers aren't
      given the information they need to manage the complex care regimens of family
      members. This series of articles and accompanying videos aims to help nurses
      provide caregivers with the tools they need to manage their family member's
      health care at home.The articles in this new installment of the series provide
      simple and useful instructions that nurses should reinforce with family
      caregivers who perform wound care tasks. Each article also includes an
      informational tear sheet-Information for Family Caregivers-that contains links to
      instructional videos. To use this series, nurses should read the article first,
      so they understand how best to help family caregivers, and then encourage
      caregivers to watch the videos and ask questions. For additional information, see
      Resources for Nurses.

PMID- 29596260
TI  - HPV Vaccination and Sexual Behaviors in Adolescents and Young Women.
AB  - According to this study.

PMID- 29596261
TI  - Money Spent on Social Services Improves Health Outcomes.
AB  - According to this study.

PMID- 29596262
TI  - Parenting Program May Prevent Obesity in Young Children.
AB  - According to this study.

PMID- 29596263
TI  - No Fracture Benefit with Vitamin D, Calcium Supplements.
AB  - According to this study.

PMID- 29596264
TI  - Easter Egg Hunt on the Oncology Unit.
AB  - The smallest gesture has the capacity to create expansive love.

PMID- 29596265
TI  - A Multidisciplinary Discharge Timeout Checklist Improves Patient Education and
      Captures Discharge Process Errors.
AB  - OBJECTIVE: To design and implement a discharge timeout checklist, and to assess
      its effects on patients' understanding as well as the potential impact on
      preventable medical errors surrounding hospital discharges to home. METHODS:
      Based on the structure successfully used for surgical procedures and using the
      Model for Improvement framework, we designed a discharge checklist to review and
      assess patients' understanding of discharge medications, catheters, home care
      plans, follow-up, symptoms, and who to call with problems after discharge. In
      parallel, we developed a process of integrating the checklist into the discharge
      process after routine discharge procedures were completed. We used the checklists
      to assess patients' level of understanding and need for additional education as
      well as changes in discharge documentation; we also noted whether good catches of
      significant errors in the discharge process occurred. RESULTS: Over 6 months of
      study, 190 discharge timeouts out of 429 eligible discharges were completed.
      Additional education was provided in 53 of 190 discharge timeouts (27.8%), with
      62% of this education being related to medications. Twenty-one (11.1%) discharge
      timeouts resulted in at least one change to the discharge documentation or a good
      catch. CONCLUSIONS: A multidisciplinary discharge timeout directly involving the
      patient can be effective in targeting additional areas for patient education and
      in potentially reducing preventable adverse events.

PMID- 29596266
TI  - The Utility of Failure Modes and Effects Analysis of Consultations in a Tertiary,
      Academic, Medical Center.
AB  - BACKGROUND: Failure modes and effects analysis (FMEA) is a tool used to identify
      potential risks in health care processes. We used the FMEA tool for improving the
      process of consultation in an academic medical center. METHODS: A team of 10
      staff members-5 physicians, 2 quality experts, 2 organizational consultants, and
      1 nurse-was established. The consultation process steps, from ordering to
      delivering, were computed. Failure modes were assessed for likelihood of
      occurrence, detection, and severity. A risk priority number (RPN) was calculated.
      An interventional plan was designed according to the highest RPNs. Thereafter, we
      compared the percentage of completed computer-based documented consultations
      before and after the intervention. RESULTS: The team identified 3 main categories
      of failure modes that reached the highest RPNs: initiation of consultation by a
      junior staff physician without senior approval, failure to document the
      consultation in the computerized patient registry, and asking for consultation on
      the telephone. An interventional plan was designed, including meetings to update
      knowledge of the consultation request process, stressing the importance of
      approval by a senior physician, training sessions for closing requests in the
      patient file, and reporting of telephone requests. The number of electronically
      documented consultation results and recommendations significantly increased (75%)
      after intervention. CONCLUSION: FMEA is an important and efficient tool for
      improving the consultation process in an academic medical center.

PMID- 29596267
TI  - A Stewardship Program to Optimize the Use of Inhaled Nitric Oxide in Pediatric
      Critical Care.
AB  - PURPOSE: Inhaled nitric oxide (iNO) is a pulmonary vasodilator that is approved
      for use in term and near-term neonates with hypoxic respiratory failure
      associated with evidence of pulmonary hypertension. However, it is commonly used
      in infants and children to treat a variety of other cardiopulmonary diseases
      associated with pulmonary hypertension and hypoxic respiratory failure. In
      critically ill children, iNO therapy may be continued for a prolonged period, and
      this increases the risk for adverse consequences including toxicity and
      unnecessary costs. We implemented an iNO Stewardship Program with the aim of
      improving adherence to guidelines and reducing unnecessary iNO utilization.
      METHODS: Between April 1, 2011, and March 31, 2015, a before and after cohort
      study was conducted at The Hospital for Sick Children. Prospective iNO usage and
      outcome variables in the poststewardship period were examined. RESULTS: Patient
      characteristics and outcomes were similar before and after stewardship
      implementation. The number of iNO therapy courses were also similar in the before
      and after period. Inhaled nitric oxide utilization in the pediatric intensive
      care unit and the cardiac critical care unit decreased from 15 765 hours in the
      prestewardship period (April 2011 to March 2013) to 10 342 hours in the
      poststewardship period (April 2013 to March 2015), with significant improvement
      in adherence to the iNO guideline and a small decrease in expenditure (3%).
      CONCLUSION: Implementation of the iNO Stewardship was successful at reducing
      overall iNO utilization. This quality improvement initiative helped us optimize
      practice and subsequently expand the methodology to inform the clinical
      indication for iNO.

PMID- 29596268
TI  - Characteristics of Volunteer Coaches in a Clinical Process Improvement Program.
AB  - INTRODUCTION: The Partners Clinical Process Improvement Leadership Program
      provides quality improvement training for clinicians and administrators,
      utilizing graduates as volunteer peer coaches for mentorship. We sought to
      understand the factors associated with volunteer coach participation and gain
      insight into how to improve and sustain this program. METHODS: Review of coach
      characteristics from course database and survey of frequent coaches. RESULTS: Out
      of 516 Partners Clinical Process Improvement Leadership Program graduates from
      March 2010 to June 2015, 117 (23%) individuals volunteered as coaches. Sixty-one
      (52%) individuals coached once, 31 (27%) coached twice, and 25 (21%) coached 3 or
      more times. There were statistically significant associations between coaching
      and occupation (P = .005), Partners Clinical Process Improvement Leadership
      Program course taken (P = .001), and course location (P = .007). Administrators
      were more likely to coach than physicians (odds ratio: 1.75, P = .04). Reasons
      for volunteering as a coach included further development of skills, desire to
      stay involved with program, and enjoying mentoring. Reasons for repeated coaching
      included maintaining quality improvement skills, expanding skills to a wider
      variety of projects, and networking. CONCLUSIONS: A peer graduate volunteer coach
      model is a viable strategy for interprofessional quality improvement mentorship.
      Strategies that support repeat coaching and engage clinicians should be promoted
      to ensure an experienced and diversified group of coaches.

PMID- 29596269
TI  - VA Quality Scholars Quality Improvement Coach Model to Facilitate Learning and
      Success.
AB  - Despite the increase in quality improvement (QI) education both in practice and
      in health professions' education, gaps exist in the usefulness and success of QI
      projects. Barriers to successful QI are a result of delays in implementation,
      teamwork issues, and lack of QI knowledge. These barriers can be addressed using
      a QI Coach. A QI Coach is an expert in QI principles who has excellent
      communication and collaboration skills, and is experienced with organizational
      policies. The purpose of this article is to (a) describe the VA Quality Scholars
      (VAQS) QI Coach Model that includes the role of a coach and effective coaching
      strategies and (b) discuss lessons learned from the application of the VAQS QI
      Coach Model. The QI Coach facilitates success by providing novice QI teams with
      practical skills, encouragement, and support.

PMID- 29596270
TI  - An Assessment of Organizational Health Literacy Practices at an Academic Health
      Center.
AB  - BACKGROUND: Organizational health literacy is the degree to which an organization
      considers and promotes the health literacy of patients. Addressing health
      literacy at an organizational level has the potential to have a greater impact on
      more health consumers in a health system than individual-level approaches.
      OBJECTIVE: The purpose of this study was to assess health care practices at an
      academic health center using the 10 attributes of a health-literate health care
      organization. METHODS: Using a survey research design, the Health Literate
      Healthcare Organization 10-Item Questionnaire was administered online using total
      population sampling. Employees (N = 10 300) rated the extent that their
      organization's health care practices consider and promote patients' health
      literacy. Differences in responses were assessed using factorial analysis of
      variance. RESULTS: The mean response was 4.7 on a 7-point Likert scale. Employee
      training and communication about costs received the lowest ratings. Univariate
      analyses revealed that there were no statistically significant differences (P =
      .05) by employees' health profession, years of service, or level of patient
      contact. There were statistically significant differences by highest education
      obtained with lowest ratings from employees with college degrees. CONCLUSIONS:
      Survey responses indicate a need for improvements in health care practices to
      better assist patients with inadequate health literacy.

PMID- 29596271
TI  - Health Literacy Demands of Patient-Reported Evaluation Tools in Orthopedics: A
      Mixed-Methods Case Study.
AB  - BACKGROUND: In response to an assessment of organizational health literacy
      practices at a major academic health center, this case study evaluated the health
      literacy demands of patient-reported outcome measures commonly used in orthopedic
      surgery practices to identify areas for improvement. METHODS: A mixed-methods
      approach was used to analyze the readability and patient feedback of orthopedic
      patient-reported outcome materials. Qualitative results were derived from focus
      group notes, observations, recordings, and consensus documents. Results were
      combined to formulate recommendations for quality improvement. RESULTS:
      Readability results indicated that narrative portions of sample patient outcome
      tools were written within or below the recommended eighth-grade reading level (=
      5.9). However, document literacy results were higher than the recommended reading
      level (= 9.8). Focus group results revealed that participants had consensus on 8
      of 12 plain language best practices, including use of bullet lists and jargon or
      technical words in both instruments. CONCLUSIONS: Although the typical
      readability of both instruments was not exceedingly high, appropriate readability
      formula and assessment methods gave a more comprehensive assessment of true
      readability. In addition, participant feedback revealed the need to reduce jargon
      and improve formatting to lessen the health literacy demands on patients. As
      clinicians turn more toward patient-reported measures to assess health care
      quality, it is important to consider the health literacy demands that are
      inherent in the instruments they are given in our health systems.

PMID- 29596273
TI  - Using Telehealth to Provide the Right Care at the Right Time-Anywhere.

PMID- 29596272
TI  - Saving the Lifesavers: Using Improvement Science to Better Clinician Well-being.

PMID- 29596277
TI  - Jeremy Fairbank: 2018 ISSLS Wiltse Lifetime Achievement Award.

PMID- 29596278
TI  - Changes in Lumbar Endplate Area and Concavity Associated With Disc Degeneration.
AB  - STUDY DESIGN: Retrospective image-based analysis. OBJECTIVE: To measure endplate
      three-dimensional (3D) geometry, endplate changes in vivo and to investigate
      correlations between disc degeneration and endplate 3D geometry dependent on
      symptoms of low back pain (LBP). SUMMARY OF BACKGROUND DATA: It has been
      hypothesized that alteration of load transmission from the nucleus pulposus to
      the annulus fibrosus affects vertebral endplate geometry. METHODS: 3D surface
      models of inferior/superior lumbar endplates were created from computed
      tomography scans of n = 92 volunteers with and without LBP. Disc degeneration was
      evaluated using Pfirrmann scale. Concavity in both coronal and sagittal planes
      was assessed with the Concavity Index (unitless; larger than 1: concave; flat: 1;
      and less than 1: convex, respectively). Endplate area and disc height
      distribution were computed and the effects from demographics and spinal
      degeneration were sought with an analysis of variance model. RESULTS: Both
      sagittal and coronal planes revealed significantly decreased concavity in those
      with terminal grade 5 disc degeneration (mean 0.833 +/- 0.235) compared to the
      other grades in the cohort. Older subjects presented with larger endplate areas
      than the younger subjects (P = 0.0148) at L4-S1. Overall, symptomatic subjects
      had significantly larger endplate areas (P = 0.022), especially at the lower
      lumbar levels (P < 0.001). Analysis of variance showed that sex, disc level, disc
      degeneration grade, and disc height reached significance (P < 0.0001) as
      influential parameters in both Concavity Index cases. CONCLUSION: With advancing
      intervertebral disc degeneration, endplates become more convex over time in both
      sagittal and coronal planes. Our findings implicate the endplate changes with
      advancing disc degeneration in the shift in load transmission from the nucleus
      pulposus to the annulus fibrosus, resulting in changes within the curvature of
      the endplates. This is also the first study to describe the direct impact of age,
      sex, and LBP on vertebral endplate anatomy. LEVEL OF EVIDENCE: 5.

PMID- 29596279
TI  - Electronic Medical Record in the ED: A Cross-Sectional Survey of Resuscitation
      Documentation Practices and Perceptions Among Emergency Department Clinicians.
AB  - OBJECTIVES: The aims of this study were to describe current practices in nursing
      documentation of trauma and medical resuscitations across emergency departments
      (EDs) and explore physicians' and nurses' perceptions of electronic medical
      record (EMR) use for nursing documentation of resuscitations. METHODS: An
      anonymous Web-based survey was developed and distributed to a convenience sample
      of ED physicians and nurses in the United States. RESULTS: Of 438 respondents,
      154 were nurses; 97.2% of respondents reported that their EDs use EMR generally.
      Of those, 51.2% use EMR to document resuscitations. When describing documentation
      processes, 19% (95% confidence interval [CI], 15%-23%) reported direct
      documentation on EMR, 18% (95% CI, 14%-21%) reported documenting on paper before
      transferring to EMR, and 22% (95% CI, 18%-26%) reported simultaneously
      documenting on EMR and paper. Thirty-seven percent of respondents reported that
      the "documentor" frequently performs other tasks during resuscitations. Few
      nurses (39.6%) and physicians (26.4%) perceived EMR as more efficient than paper.
      Nurses (66.2%) and physicians (51.8%) perceived paper as more complete than EMR.
      Few nurses (31.6%) and physicians (25.6%) agreed that paper would facilitate
      continuity of care better than EMR. No associations between nurses' perceptions
      of EMR, professional experience, or technology use were found. CONCLUSIONS:
      Although EMR adoption was common among respondents, only half reported using EMR
      to document resuscitations. Even fewer reported documenting directly on EMR,
      whereas a significant proportion reported processes that may be inefficient,
      redundant, or prone to errors. Respondents endorsed mostly negative perceptions
      of EMR. Our findings suggest that there may be factors inherent to resuscitations
      and the existing EMR interfaces that render documenting resuscitations on EMR
      uniquely challenging.

PMID- 29596280
TI  - Adolescent Sexual Behavior and Emergency Department Use.
AB  - OBJECTIVES: The objective of this study was to determine whether adolescents in
      emergency departments (EDs) who report engaging in high-risk sexual behaviors are
      less likely to identify a primary care provider (PCP) and more likely to access
      the ED than their sexually inexperienced peers. METHODS: This was a secondary
      analysis of adolescents presenting to a pediatric ED with non-sexually
      transmitted infection (STI)-related complaints who completed surveys to assess
      sexual behavior risk and health care access. We measured differences in self
      reported PCP identification, preferential use of the ED, and number of ED visits
      over a 12-month period by sexual experience. Secondary outcomes included
      clinician documented sexual histories and STI testing. RESULTS: Of 758 patients
      meeting inclusion criteria, 341 (44.9%) were sexually experienced, and of those,
      129 (37.8%) reported engaging in high-risk behavior. Participants disclosing high
      risk behavior were less likely to identify a PCP (adjusted odds ratio, 0.5; 95%
      confidence interval [CI], 0.3-0.9), more likely to prefer the ED for acute care
      issues (adjusted odds ratio, 1.6; 95% CI, 1.0-2.6), and had a higher rate of ED
      visits (adjusted relative risk, 1.2; 95% CI, 1.0-1.3) compared with sexually
      inexperienced peers. Among patients disclosing high-risk behavior, 10.9% had
      clinician-documented sexual histories and 2.6% underwent STI testing. CONCLUSION:
      Adolescents who reported engaging in high-risk sexual behaviors were less likely
      to identify a PCP, as well as more likely to prefer ED-based care and make more
      ED visits. However, ED clinicians infrequently obtained sexual histories and
      performed STI testing in asymptomatic youth, thereby missing opportunities to
      screen high-risk adolescents who may lack access to preventive care.

PMID- 29596281
TI  - Chikungunya in a Pediatric Traveler.
AB  - Chikungunya is a mosquito-transmitted virus found primarily in Africa and Asia.
      In late 2013, chikungunya virus emerged in the Western hemisphere, spreading from
      the Caribbean to South, Central, and North America (MMWR Morb Mortal Wkly Rep.
      2014;63:1121-1128). Symptoms can be similar to nonspecific viral presentations
      including fever, joint pain, joint swelling, and rash. The diagnosis of
      infectious tropical diseases in the emergency department often requires a high
      index of suspicion, given the nonspecific early findings that characterize many
      of these tropical diseases. This report presents a case of chikungunya in a
      pediatric patient traveling from Guatemala to the United States. Proper
      recognition of infection and diagnosis are vital from a public health
      perspective. Considering patients will remain viremic for up to a week and
      potentially expose local mosquitoes to infection, it is important to educate the
      patient on mosquito bite prevention in geographic areas of the United States
      where competent mosquito vectors exist as a means of avoiding further spread.

PMID- 29596282
TI  - Intimate Partner Violence Educational Materials in the Acute Care Setting:
      Acceptability and Impact on Female Caregiver Attitudes Toward Screening.
AB  - OBJECTIVES: This study aimed to determine acceptability of intimate partner
      violence (IPV) materials and effect of the materials on caregiver attitudes
      toward IPV screening. METHODS: We used an anonymous computerized survey to assess
      approval of IPV materials and screening, and willingness to disclose IPV in
      response to screening among mothers bringing a child to an urban pediatric
      emergency department or 2 suburban pediatric urgent care centers affiliated with
      a free-standing academic children's hospital. We compared responses between
      participants recruited before and after display of the IPV materials, as well as
      between subgroups, using chi tests. RESULTS: A total of 522 participated
      (predisplay, n = 261; postdisplay, n = 261). More subjects in the postdisplay
      group approved of display of IPV materials in pediatric emergency
      department/urgent care center restrooms (94% pre vs 98% post, P = 0.04) and
      examination rooms (94% pre vs 98% post, P = 0.01). We found no differences in
      acceptability of IPV screening between the pre and post groups (73% pre and post,
      P = 0.92). Willingness to disclose IPV in response to screening was higher in the
      postdisplay group for those with a personal IPV history (55% pre, 73% post; P =
      0.02), African Americans (60% pre, 78% post; P = 0.02), and those with a high
      school degree or less education (66% pre, 77% post; P = 0.04). CONCLUSIONS:
      Intimate partner violence materials in this study were acceptable to most
      participants and did not negatively impact attitudes toward IPV screening or
      willingness to disclose IPV. Display of IPV materials should be considered as a
      component of IPV intervention.

PMID- 29596283
TI  - Pediatric Sigmoid Volvulus.
AB  - Sigmoid volvulus is an extremely rare cause of abdominal pain in children. More
      commonly seen in older adults, an SV occurs when a redundant loop of sigmoid
      wraps around its elongated, narrow mesentery causing obstruction and ischemia to
      the affected bowel segment. Children usually present with abdominal pain, nausea,
      and abdominal distension. Presentations may be acute or chronic with a history of
      episodic constipation or abdominal distension. The treatment plan includes an
      initial reduction of the volvulus via sigmoidoscopy with rectal biopsy to rule
      out Hirschsprung disease; however, operative management to remove the dilated
      sigmoid colon may be required in the setting of recurrence or confirmed
      Hirschsprung disease. Although rare, SV should be considered in a child
      presenting with abdominal pain as a missed diagnosis can have high potential
      morbidity and mortality.

PMID- 29596284
TI  - A Case of Wernicke Encephalopathy Developing After Ileal Bypass Surgery.
AB  - Wernicke encephalopathy is an acute neurological problem resulting from thiamine
      deficiency and manifesting with mental confusion, oculomotor dysfunction, and
      ataxia. It is associated with alcohol dependence in adults. Preparatory factors
      include hyperemesis gravidarum, prolonged diarrhea, prolonged parental nutrition
      without vitamin support, absorption disorders, anorexia, cancer, and
      chemotherapy. Failure to consider the clinical findings and preparatory factors
      of this disease, which is rare in children, can delay diagnosis. This report
      describes a case of Wernicke encephalopathy developing in a patient with brid
      ileus and receiving total parenteral nutrition after partial ileal bypass
      surgery. The patient's clinical and cranial magnetic resonance findings were
      compatible with Wernicke encephalopathy. Although these are not widespread,
      typical ocular findings for Wernicke encephalopathy were present. Dramatic
      improvements were observed in clinical, ocular, and cranial magnetic resonance
      findings after treatment.

PMID- 29596285
TI  - Rising Clinical Burden of Psychiatric Visits on the Pediatric Emergency
      Department.
AB  - OBJECTIVE: The mental health epidemic in pediatrics has resulted in a growing
      clinical burden on the health care system, including pediatric emergency
      departments (PED). Our objective was to describe the changing characteristics of
      visits to an urban PED, in particular length of stay, for emergency psychiatric
      evaluations (EPEs) over a 10-year period. METHODS: A retrospective study of
      children with an EPE in the PED at a large urban quaternary care children's
      hospital was performed during two discrete periods a decade apart: July 1, 2003
      June 30, 2004 (period 1) and July 1, 2013-June 30, 2014 (period 2). Visit
      information, including length of stay and demographic data, were compared between
      groups. RESULTS: There was a significant increase in the percentage of PED visits
      for EPE from period 1 to period 2 (1.1% vs 2.2% P < 0.0001). Overall, the median
      (interquartile range [IQR]) length of stay for children requiring an EPE
      increased significantly for all visits (5.3 [3.2-15.4] hours vs 17.0 [6.0-26.0]
      hours, P < 0.0001), including for patients who were admitted (17.8 [7.4-24.6]
      hours vs 27.0 [21.0-36.0] hours, P < 0.0001) and for those who were discharged
      (4.5 [2.8-7.7] hours vs 8 [5-20] hours, P < 0.0001). CONCLUSIONS: Over a decade,
      the percentage of children with an EPE has doubled, with a significant increase
      in the amount of time spent in the PED. This highlights a continued surge in the
      utilization of PED resources for EPE.

PMID- 29596286
TI  - Acute Terminal Ileitis in Children: A Retrospective Study in Pediatric Emergency
      Department.
AB  - OBJECTIVES: This study aims to describe the clinical presentation and outcome of
      patients diagnosed with acute ileitis in our pediatric emergency department.
      METHODS: We performed a retrospective study of all patients diagnosed with
      terminal ileitis by abdominal ultrasonography findings in our pediatric emergency
      department, over the years 2013 and 2014. Patients with previous diagnosis of
      inflammatory bowel disease (IBD) were excluded. Data collected were clinical,
      radiological, and laboratory data at diagnosis; outcome including hospitalization
      care; and outpatient follow-up in pediatric gastroenterology and/or primary care.
      RESULTS: A total of 20 cases were retrieved and studied. All of them presented
      with abdominal pain, 65% located in the right lower quadrant. Leukocyte count, C
      reactive protein, and fibrinogen levels (means, 12,889; 4/MUL; 50.1 mg/L; and 575
      mg/dL, respectively) were above normal range. Hemoglobin and platelet count were
      normal. A microbial cause of ileitis was found in 3 cases (Yersinia
      enterocolitica, Campylobacter jejuni, and Adenovirus). Nine patients were
      referred to a pediatric gastroenterology unit. No cases of IBD were found.
      CONCLUSIONS: Acute ileitis is a rare and benign cause of abdominal pain in the
      pediatric emergency department. The main intervention on initial assessment is to
      rule out potentially severe causes of abdominal pain that could benefit of an
      emergency surgical procedure. In contrast with adults and adolescents, acute
      ileitis in children does not have a clear association with development of IBD.

PMID- 29596287
TI  - Moments: Finding Passion and Purpose.

PMID- 29596288
TI  - Management of Intracranial Pressure: Part I: Pharmacologic Interventions.
AB  - Dangerous, sustained elevation in intracranial pressure (ICP) is a risk for any
      patient following severe brain injury. Intracranial pressure elevations that do
      not respond to initial management are considered refractory to treatment, or
      rICP. Patients are at significant risk of secondary brain injury and permanent
      loss of function resulting from rICP. Both nonpharmacologic and pharmacologic
      interventions are utilized to intervene when a patient experiences either
      elevation in ICP or rICP. In part 1 of this 2-part series, pharmacologic
      interventions are discussed. Opioids, sedatives, osmotic diuretics, hypertonic
      saline solutions, and barbiturates are drug classes that may be used in an
      attempt to normalize ICP and prevent secondary injury. Nursing care of these
      patients includes collaboration with an interprofessional team and is directed
      toward patient and family comfort. The utilization of an evidence-based guideline
      for the management of rICP is strongly encouraged to improve patient outcomes.

PMID- 29596289
TI  - Identification and Management of Acute Cardiac Tamponade.
AB  - Although incidence is rare, acute cardiac tamponade (CT) is a cardiovascular
      condition often resulting in a high mortality rate. In acute CT, rapid
      accumulation of fluid occurs in the pericardial sac and prevents the heart's
      chambers from adequately filling with blood, leading to reduced diastolic
      filling, diminished stroke volumes, and subsequent hemodynamic instability.
      Health care providers should be aware of at-risk patients and the earliest signs
      and symptoms because an acute CT is considered a medical emergency.

PMID- 29596290
TI  - Use of Recruitment Maneuvers in Patients With Acute Respiratory Distress
      Syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a deadly complication in critically
      ill patients that causes significant morbidity and mortality. Patients with ARDS
      are seen across intensive care unit settings, with treatment being largely
      supportive involving techniques through mechanical ventilation. Using low-tidal
      volume ventilation is a standard of practice for patients with ARDS, as a lung
      protection strategy; however, alveolar decruitment may occur. Recruitment
      maneuvers can recruit collapsed alveoli and promote oxygenation. There are
      several methods of recruitment maneuvers-each with varying levels and durations
      of positive end-expiratory pressure. It is still uncertain which method is the
      best. The evidence for the efficacy of recruitment maneuvers has shown a decrease
      in intensive care unit mortality, but strong evidence is lacking for its routine
      use, and the decision to use recruitment maneuvers should be based on individual
      characteristics and responses. This article reviews management of ARDS,
      recruitment maneuver techniques, and clinical application through a case study.

PMID- 29596291
TI  - Interprofessional Simulations Promote Knowledge Retention and Enhance Perceptions
      of Teamwork Skills in a Surgical-Trauma-Burn Intensive Care Unit Setting.
AB  - BACKGROUND: The current state of health care encompasses highly acute, complex
      patients, managed with ever-changing technology. The ability to function
      proficiently in critical care relies on knowledge, technical skills, and
      interprofessional teamwork. Integration of these factors can improve patient
      outcomes. Simulation provides "hands-on" practice and allows for the integration
      of teamwork into knowledge/skill training. However, simulation can require a
      significant investment of time, effort, and financial resources. The Institute of
      Medicine recommendations from 2015 include "strengthening the evidence base for
      interprofessional education (IPE)" and "linking IPE with changes in collaborative
      behavior." In one surgical-trauma-burn intensive care unit (STBICU), no IPE
      existed. The highly acute and diverse nature of the patients served by the unit
      highlights the importance of appropriate training. This is heightened during
      critical event situations where patients deteriorate rapidly and the team
      intervenes swiftly. PURPOSE: The aims of this study were to (1) evaluate
      knowledge retention and analyze changes in perceptions of teamwork among nurses
      and resident physicians in a STBICU setting after completion of an
      interprofessional critical event simulation and (2) provide insight for future
      interprofessional simulations (IPSs), including the ideal frequency of such
      training, associated cost, and potential effect on nursing turnover. DESIGN: A
      comparison-cohort pilot study was developed to evaluate knowledge retention and
      analyze changes in perceptions of teamwork. METHODS: A 1-hour critical event IPS
      was held for nurses and resident physicians in a STBICU setting. A traumatic
      brain injury patient with elevated intracranial pressure, rapid deterioration,
      and cardiac arrest was utilized for the simulation scenario. The simulation
      required the team to use interventions to reduce elevated intracranial pressure
      and then perform cardiac resuscitation according to Advanced Cardiac Life Support
      guidelines. A semistructured debriefing guided by the TENTS tool highlighted
      important aspects of teamwork. Participants took knowledge and Teamwork Skills
      Scale (TSS) pretests, posttests, and 1-month posttests. Mean scores were
      calculated for each time point (pre, post, and 1-month post), and paired t tests
      were used to evaluate changes. RESULTS: Mean knowledge test and TSS scores both
      significantly increased after the simulation and remained significantly elevated
      at 1-month follow-up. Participants recommended retraining intervals of 3 to 6
      months. Cost of each simulation was estimated to be $324.44. Analysis of nursing
      turnover rates did not demonstrate a statistically significant reduction in
      turnover; however, confounding factors were not controlled for. CONCLUSION:
      Significant improvements on both knowledge test and TSS scores demonstrate the
      effectiveness of the intervention, and retention of the information gained and
      teamwork skills learned. Participants valued the intervention and recommended to
      increase the frequency of training. Future studies should develop a framework for
      "best practice" IPS, analyze the relationship with nursing turnover, and
      ultimately seek correlations between IPS and improved patient outcomes.

PMID- 29596292
TI  - Informing Leadership Models: Nursing and Organizational Characteristics of
      Neonatal Intensive Care Units in Freestanding Children's Hospitals.
AB  - BACKGROUND: Neonatal intensive care units (NICUs) located in freestanding
      children's hospitals may exhibit significant variation in nursing and
      organizational characteristics, which can serve as opportunities for
      collaboration to understand optimal staffing models and linkages to patient
      outcomes. OBJECTIVES: Adopting methods used by Hickey et al in pediatric
      cardiovascular critical care, the purpose of this study was to provide a
      foundational description of the nursing and organizational characteristics for
      NICUs located in freestanding children's hospitals in the United States. METHODS:
      Clinical nurse leaders in NICUs located in freestanding children's hospitals were
      invited to participate in an electronic cross-sectional survey. Descriptive
      analyses were used to summarize nursing and organizational characteristics.
      RESULTS: The response rate was 30% (13/43), with 69.2% of NICUs classified as
      level III/IV and 30.8% classified as level II/III. Licensed bed capacity varied
      significantly (range, 24-167), as did the proportion of full-time equivalent
      nurses (range, 71.78-252.3). Approximately three-quarters of staff nurses held
      baccalaureate degrees or higher. A quarter of nurses had 16 or more years (26.3%)
      of experience, and 36.9% of nurses had 11 or more years of nursing experience.
      Nearly one-third (29.2%) had 5 or less years of total nursing experience. Few
      nurses (10.6%) held neonatal specialty certification. All units had nurse
      educators, national and unit-based quality metrics, and procedural checklists.
      CONCLUSION: This study identified (1) variation in staffing models signaling an
      opportunity for collaboration, (2) the need to establish ongoing processes for
      sites to participate in future collaborative efforts, and (3) survey
      modifications necessary to ensure a more comprehensive understanding of nursing
      and organizational characteristics in freestanding children's hospital NICUs.

PMID- 29596294
TI  - Family Presence During Resuscitation: Physicians' Perceptions of Risk, Benefit,
      and Self-Confidence.
AB  - BACKGROUND: Families often desire proximity to loved ones during life-threatening
      resuscitations and perceive clear benefits to being present. However, critical
      care nurses and physicians perceive risks and benefits. Whereas research is
      accumulating on nurses' perceptions of family presence, physicians' perspectives
      have not been clearly explicated. Psychometrically sound measures of physicians'
      perceptions are needed to create new knowledge and enhance collaboration among
      critical care nurses and physicians during resuscitation events. OBJECTIVE: This
      study tests 2 new instruments that measure physicians' perceived risks, benefits,
      and self-confidence related to family presence during resuscitation. METHODS: By
      a correlational design, a convenience sample of physicians (N = 195) from diverse
      clinical specialties in 1 hospital in the United States completed the Physicians'
      Family Presence Risk-Benefit Scale and Physicians' Family Presence Self
      confidence Scale. RESULTS: Findings supported the internal consistency
      reliability and construct validity of both new scales. Mean scale scores
      indicated that physicians perceived more risk than benefit and were confident in
      managing resuscitations with families present, although more than two-thirds
      reported feeling anxious. Higher self-confidence was significantly related to
      more perceived benefit and less perceived risk (P = .001). Younger physicians,
      family practice physicians, and physicians who previously had invited family
      presence expressed more positive perceptions (P = .05-.001). DISCUSSION: These 2
      new scales offer a means to assess key perceptions of physicians related to
      family presence. Further testing in diverse physician populations may further
      validate the scales and yield knowledge that can strengthen collaboration among
      critical care nurses and physicians and improve patient and family outcomes.

PMID- 29596296
TI  - Increasing Access to Palliative Care Services in the Intensive Care Unit.
AB  - BACKGROUND: The Institute of Medicine's report, Dying in America, highlights the
      critical need for the widespread implementation of palliative care to improve end
      of-life care. Approximately 20% of all deaths in America occur during or shortly
      after an intensive care unit (ICU) admission; therefore, it is important for
      critical care units to have systems in place to facilitate patient access to
      palliative care services. OBJECTIVES: The aim of this quality improvement (QI)
      project was to develop and implement a palliative care screening tool using
      evidence-based triggers to help increase the proportion of palliative care
      consultations in the ICU setting. METHODS: A QI project was designed and
      implemented in a 14-bed medical-surgical ICU in the southeastern United States
      using the Plan-Do-Study-Act cycle. A palliative care screening tool was developed
      by an interdisciplinary team of key stakeholders in the ICU using evidence-based
      triggers, and staff were educated on the intervention. The proportion of ICU
      patients who received a palliative care consultation was compared preintervention
      and postintervention to determine whether the QI project contributed to an
      increased proportion of palliative care consultations. RESULTS: The proportion of
      palliative care consultations among patients admitted to the ICU by the pulmonary
      critical care team increased from 1 of 10 preintervention to 3 of 10
      postintervention, resulting in a promising increase in patients receiving
      palliative care services consistent with evidence-based recommendations.
      CONCLUSION: The use of an evidence-based screening tool to trigger palliative
      care consultation in the ICU setting can aid in increasing the proportion of
      critical care patients who receive a palliative care referral. The increase in
      the proportion of palliative care referrals by the pulmonary critical care
      service warrants expansion of the intervention to include additional medical
      subspecialists who frequently admit patients in this ICU setting. Further
      assessment of the intervention is warranted to determine whether the screening
      tool can aid in increasing palliative care consultations for more patients
      admitted to the hospital's ICU.

PMID- 29596297
TI  - Innovation in Clinical Practice: A Preliminary Study on Delirium Assessment in
      Intensive Care Unit Using an Application for Smartphone.

PMID- 29596298
TI  - A Single-Center Retrospective Validation Study of the American College of
      Radiology Thyroid Imaging Reporting and Data System.
AB  - OBJECTIVE: This study aimed to evaluate a new risk stratification system, the
      American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI
      RADS), published in 2017. MATERIALS AND METHODS: From January 2015 to December
      2016, 1033 thyroid nodules in 1013 patients who had undergone sonography and
      thyroid surgery or fine-needle aspiration (FNA) in our hospital were included.
      The sonographic features were described in a standard manner and analyzed
      according to the white paper of the ACR TI-RADS Committee. Nodules were assigned
      points for each feature, and the points were totaled to determine the final TI
      RADS levels. RESULTS: Of the 1033 nodules, 725 were benign and 308 were malignant
      proven by operation or FNA. The malignant risk was associated with the
      composition, echogenicity, shape, margins, and echogenic foci of the nodules (P <
      0.001). The calculated risk of malignancy was higher in nodules with
      macrocalcifications than those with peripheral calcifications, which is different
      from the ACR TI-RADS. The calculated malignancy rates of nodules with TR5, TR4,
      TR3, and TR2 were 67.1%, 13.0%, 1.1%, and 0%, respectively, which showed a higher
      malignant risk than the suggested threshold of TR5 in the ACR TI-RADS. Six
      nodules with TR4 recommended for no follow-up and 55 nodules with TR5 recommended
      for follow-up were malignant with cervical lymph node metastasis. CONCLUSIONS:
      The ACR TI-RADS provides effective malignancy risk stratification for thyroid
      nodules and was useful for the decision for FNA. However, the points assigned for
      echogenic foci, the set of the TI-RADS risk thresholds, and FNA thresholds may
      need more consideration and prospective validation.

PMID- 29596299
TI  - A Narrative Review on Contrast-Enhanced Ultrasound in Aortic Endograft Endoleak
      Surveillance.
AB  - Endovascular repair of abdominal aortic aneurysms have been performed
      successfully since 1991. However, 20% to 50% of these patients may develop an
      endoleak or continued aneurysmal sac expansion or perfusion despite stent graft
      coverage. Current recommendations suggest lifelong surveillance with computed
      tomographic angiography (CTA) at least 1 month after intervention and yearly
      after that. In select patients with a stable aneurysm sac on computed tomography
      performed 1 year after treatment, future screening could be performed with
      ultrasonography. However, color Doppler ultrasound can fail to detect as many as
      31% of endoleaks. Contrast-enhanced ultrasound (CEUS) provides an alternative
      approach to excluded aneurysm sac follow-up imaging. The Society for Vascular
      Surgery notes a need for further research on the role of CEUS in endovascular
      aortic repair surveillance. The European Federation of Societies for Ultrasound
      in Medicine and Biology suggests that early results are promising. Meta-analyses
      report pooled sensitivities and specificities of CEUS compared with CTA for the
      detection of endoleak between 89% and 98% and 86% and 88%, respectively. Owing to
      the dynamic flow information it provides, CEUS may actually be more sensitive
      than CTA at detection and characterization in select circumstances. Challenges
      with adoption, patient selection, and operator dependency remain, but current and
      future research suggests a role for CEUS in endoleak surveillance.

PMID- 29596300
TI  - Quantitative Assessment of Thyroid, Submandibular, and Parotid Glands Elasticity
      With Shear-Wave Elastography in Children.
AB  - Tissue elasticity is becoming a more commonly used parameter in evaluation of
      parenchyma in inflammatory diseases. Considering the changes in the thyroid and
      salivary glands with adolescence, determination of mean elasticity ranges with a
      function of age is necessary to apply ultrasound elastography more widely in the
      pediatric population.The thyroid, submandibular, and parotid glands of 127
      healthy volunteers (66 males, 61 females; mean age = 10.3 +/- 3.9 years; range =
      3-17 years) were evaluated with shear-wave elastography.The mean elasticity
      values for the thyroid, submandibular, and parotid glands were 14.6 +/- 3.3, 11.8
      +/- 2.2, and 11.8 +/- 2.6 kPa, respectively. There was a significant positive
      correlation between age and elasticity of the thyroid, submandibular, and parotid
      glands. There was a significant correlation between age and elasticity value of
      the thyroid gland adjusted for weight and height.This study provided the baseline
      quantitative elasticity measures of thyroid, submandibular, and parotid glands,
      which would be a reference for upcoming studies. In addition, an increase in
      elasticity value in thyroid gland as a function of age independent of change in
      weight and height was demonstrated.

PMID- 29596301
TI  - Superb Microvascular Imaging of Palatine Tonsils in Healthy Children: A
      Preliminary Study.
AB  - In healthy children, the normal vascularity index (VI) values were defined for
      palatine tonsils using the superb microvascular imaging (SMI), and the
      relationship with potential factors affecting these values was assessed. This
      prospective study evaluated 74 children (age range = 3-17 years, median = 13
      years, SD = 6.4 years). The cases were divided into 3 subgroups based on age as 3
      to 6 years (preschool), 7 to 12 years (school age), and 13 to 17 years
      (adolescent). Demographic data such as sex, age, and body mass index (BMI) were
      recorded. The VI values of tonsils were measured with SMI and power Doppler (PD),
      and the correlation with descriptive data was researched. The Student t test,
      Mann-Whitney U test, and Spearman rho correlation coefficient were used. The mean
      VI values on the right tonsil were calculated as 7.5% and 2.6% and on the left
      tonsil were 6.5% and 2.3% according to SMI and PD, respectively. On SMI, the
      vascularity was similar in the preschool and school-age groups, with a
      significant reduction between the school-age and adolescent groups. As BMI
      increased, tonsil vascularity reduced on SMI and PD. There was no significant
      difference in tonsil vascularity between the sexes. The VI values were identified
      to be higher on SMI compared with PD (P = 0.001). In healthy children, the normal
      VI values for both tonsils were determined with SMI and PD. On SMI, tonsil
      vascularity reduced significantly in the transition from school age to
      adolescence. Tonsil vascularity was affected by variations in BMI.

PMID- 29596302
TI  - Diagnosing a Strong-Fault Model by Conflict and Consistency.
AB  - The diagnosis method for a weak-fault model with only normal behaviors of each
      component has evolved over decades. However, many systems now demand a strong
      fault models, the fault modes of which have specific behaviors as well. It is
      difficult to diagnose a strong-fault model due to its non-monotonicity.
      Currently, diagnosis methods usually employ conflicts to isolate possible fault
      and the process can be expedited when some observed output is consistent with the
      model's prediction where the consistency indicates probably normal components.
      This paper solves the problem of efficiently diagnosing a strong-fault model by
      proposing a novel Logic-based Truth Maintenance System (LTMS) with two search
      approaches based on conflict and consistency. At the beginning, the original a
      strong-fault model is encoded by Boolean variables and converted into Conjunctive
      Normal Form (CNF). Then the proposed LTMS is employed to reason over CNF and find
      multiple minimal conflicts and maximal consistencies when there exists fault. The
      search approaches offer the best candidate efficiency based on the reasoning
      result until the diagnosis results are obtained. The completeness, coverage,
      correctness and complexity of the proposals are analyzed theoretically to show
      their strength and weakness. Finally, the proposed approaches are demonstrated by
      applying them to a real-world domain-the heat control unit of a spacecraft-where
      the proposed methods are significantly better than best first and conflict
      directly with A* search methods.

PMID- 29596303
TI  - Phasor-Based Endogenous NAD(P)H Fluorescence Lifetime Imaging Unravels Specific
      Enzymatic Activity of Neutrophil Granulocytes Preceding NETosis.
AB  - Time-correlated single-photon counting combined with multi-photon laser scanning
      microscopy has proven to be a versatile tool to perform fluorescence lifetime
      imaging in biological samples and, thus, shed light on cellular functions, both
      in vitro and in vivo. Here, by means of phasor-analyzed endogenous NAD(P)H
      (nicotinamide adenine dinucleotide (phosphate)) fluorescence lifetime imaging, we
      visualize the shift in the cellular metabolism of healthy human neutrophil
      granulocytes during phagocytosis of Staphylococcus aureus pHrodoTM beads. We
      correlate this with the process of NETosis, i.e., trapping of pathogens by DNA
      networks. Hence, we are able to directly show the dynamics of NADPH oxidase
      activation and its requirement in triggering NETosis in contrast to other
      pathways of cell death and to decipher the dedicated spatio-temporal sequence
      between NADPH oxidase activation, nuclear membrane disintegration and DNA network
      formation. The endogenous FLIM approach presented here uniquely meets the
      increasing need in the field of immunology to monitor cellular metabolism as a
      basic mechanism of cellular and tissue functions.

PMID- 29596305
TI  - Differences in the Effects of EGCG on Chromosomal Stability and Cell Growth
      between Normal and Colon Cancer Cells.
AB  - The tea catechin epigallocatechin-3-gallate (EGCG) proved to be the most potent
      physiologically active tea compound in vitro. It possesses antioxidant as well as
      pro-oxidant properties. EGCG has the effect of inducing apoptosis of tumor cells
      and inhibiting cell proliferation. Whether this effect is associated with the
      antioxidant or pro-oxidative effects of EGCG affecting the genome stability of
      normal and cancer cells has not been confirmed. Here, we selected Human normal
      colon epithelial cells NCM460 and colon adenocarcinoma cells COLO205 to
      investigate the effects of EGCG (0&ndash;40 &mu;g/mL) on the genome stability and
      cell growth status. Chromosomal instability (CIN), nuclear division index (NDI),
      and apoptosis was measured by cytokinesis-block micronucleus assay (CBMN), and
      the expression of core genes in mismatch repair (hMLMLH1 and hMSH2) was examined
      by RT-qPCR. We found that EGCG significantly reduced CIN and apoptosis rate of
      NCM460 at all concentrations (5&ndash;40 &mu;g/mL) and treatment time, EGCG at 5
      &mu;g/mL promoted cell division; EGCG could significantly induce chromosome
      instability in COLO205 cells and trigger apoptosis and inhibition of cell
      division. These results suggest that EGCG exhibits different genetic and
      cytological effects in normal and colon cancer cells.

PMID- 29596306
TI  - Use of Iodine-Containing Dietary Supplements Remains Low among Women of
      Reproductive Age in the United States: NHANES 2011-2014.
AB  - In the United States, the American Thyroid Association recommends that women take
      a dietary supplement containing 150 &micro;g of iodine 3 months prior to
      conception and while pregnant and lactating to support fetal growth and
      neurological development. We used data from the National Health and Nutrition
      Examination Survey 2011&ndash;2014 to describe the use of dietary supplements
      with and without iodine in the past 30 days among 2155 non-pregnant, non
      lactating (NPNL) women; 122 pregnant women; and 61 lactating women. Among NPNL
      women, 45.3% (95% Confidence Interval [CI]: 42.0, 48.6) used any dietary
      supplement and 14.8% (95% CI: 12.7, 16.8) used a dietary supplement with iodine
      in the past 30 days. Non-Hispanic black and Hispanic women were less likely to
      use any dietary supplement as well as one with iodine, than non-Hispanic white or
      non-Hispanic Asian women (p < 0.05). Among pregnant women, 72.2% (95% CI: 65.8,
      78.6) used any dietary supplement; however, only 17.8% (95% CI: 11.4, 24.3) used
      a dietary supplement with iodine. Among lactating women, 75.0% (95% CI: 63.0,
      87.0) used a dietary supplement; however, only 19.0% (95% CI: 8.8, 29.2) used a
      dietary supplement with iodine. Among NPNL women using a supplement with iodine,
      median daily iodine intake was 75.0 &micro;g. Self-reported data suggests that
      the use of iodine containing dietary supplements among pregnant and lactating
      women remains low in contrast with current recommendations.

PMID- 29596304
TI  - Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and
      MicroRNA as New Treatment Candidates.
AB  - Despite great improvements in the diagnosis and treatment of neoplasms,
      metastatic disease is still the leading cause of death in cancer patients, with
      mortality rates still rising. Given this background, new ways to treat cancer
      will be important for development of improved cancer control strategies. Cdc42 is
      a member of the Rho GTPase family and plays an important role in cell-to-cell
      adhesion, formation of cytoskeletal structures, and cell cycle regulation. It
      thus influences cellular proliferation, transformation, and homeostasis, as well
      as the cellular migration and invasion processes underlying tumor formation.
      Cdc42 acts as a collection point for signal transduction and regulates multiple
      signaling pathways. Moreover, recent studies show that in most human cancers
      Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis.
      Regarding possible new treatments for cancer, miRNA and small molecules targeting
      Cdc42 and related pathways have been recently found to be effective on cancer. In
      this review, we analyze the newly recognized regulation mechanisms for Cdc42 and
      Cdc42-related signal pathways, and particularly new treatments using small
      molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may
      slow down the metastasis process, improve cancer therapy and lead to novel
      strategies for development of antineoplastic drugs.

PMID- 29596307
TI  - Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese
      Elderly Individuals: A Systematic Review and Meta-Analysis.
AB  - It remains unclear as to what extent resistance training (RT) can attenuate
      muscle loss during caloric restriction (CR) interventions in humans. The
      objective here is to address if RT could attenuate muscle loss induced by CR in
      obese elderly individuals, through summarized effects of previous studies.
      Databases MEDLINE, Embase and Web of Science were used to perform a systematic
      search between July and August 2017. Were included in the review randomized
      clinical trials (RCT) comparing the effects of CR with (CRRT) or without RT on
      lean body mass (LBM), fat body mass (FBM), and total body mass (BM), measured by
      dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs
      included in the review applied RT three times per week, for 12 to 24 weeks, and
      most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30%
      fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273]), with
      similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle
      quality, the change in strength/LBM ratio tended to be different (p = 0.07)
      following CRRT (20.9 &plusmn; 23.1%) and CR interventions (&minus;7.5 &plusmn;
      9.9%). Our conclusion is that CRRT is able to prevent almost 100% of CR-induced
      muscle loss, while resulting in FBM and BM reductions that do not significantly
      differ from CR.

PMID- 29596309
TI  - Risk Factors for Brachial Plexus Birth Injury.
AB  - Over the course of decades, the incidence of brachial plexus birth injury (BPBI)
      has increased despite advances in healthcare which would seem to assist in
      decreasing the rate. The aim of this study is to identify previously unknown risk
      factors for BPBI and the risk factors with potential to guide preventative
      measures. A case control study of 52 mothers who had delivered a child with a
      BPBI injury and 132 mothers who had delivered without BPBI injury was conducted.
      Univariate, multivariable and logistic regressions identified risk factors and
      their combinations. The odds of BPBI were 2.5 times higher when oxytocin was used
      and 3.7 times higher when tachysystole occurred. The odds of BPBI injury are
      increased when tachysystole and oxytocin occur during the mother's labor.
      Logistic regression identified a higher risk for BPBI when more than three of the
      following variables (>30 lbs gained during the pregnancy, stage 2 labor >61.5
      min, mother's age >26.4 years, tachysystole, or fetal malpresentation) were
      present in any combination.

PMID- 29596310
TI  - Biochemical Assessment and Monitoring of Mitochondrial Disease.
AB  - Mitochondrial respiratory chain (MRC) disorders have a multifaceted clinical
      presentation and genetic origin[...].

PMID- 29596308
TI  - EP4 as a Therapeutic Target for Aggressive Human Breast Cancer.
AB  - G-protein-coupled receptors (GPCRs, also called seven-transmembrane or
      heptahelical receptors) are a superfamily of cell surface receptor proteins that
      bind to many extracellular ligands and transmit signals to an intracellular
      guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor
      activates the attached G-protein by causing the exchange of Guanosine-5'
      triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in
      many physiological functions, as well as in the pathology of many diseases,
      including cancer progression and metastasis. Only a few GPCR members have been
      exploited as targets for developing drugs with therapeutic benefit in cancer.
      Present review briefly summarizes the signaling pathways utilized by the EP
      (prostaglandin E receptor) family of GPCR, their physiological and pathological
      roles in carcinogenesis, with special emphasis on the roles of EP4 in breast
      cancer progression. We make a case for EP4 as a promising newer therapeutic
      target for treating breast cancer. We show that an aberrant over-expression of
      cyclooxygenase (COX)-2, which is an inflammation-associated enzyme, occurring in
      40-50% of breast cancer patients leads to tumor progression and metastasis due to
      multiple cellular events resulting from an increased prostaglandin (PG) E2
      production in the tumor milieu. They include inactivation of host anti-tumor
      immune cells, such as Natural Killer (NK) and T cells, increased immuno
      suppressor function of tumor-associated macrophages, promotion of tumor cell
      migration, invasiveness and tumor-associated angiogenesis, due to upregulation of
      multiple angiogenic factors including Vascular Endothelial Growth Factor (VEGF)
      A, increased lymphangiogenesis (due to upregulation of VEGF-C/D), and a
      stimulation of stem-like cell (SLC) phenotype in cancer cells. All of these
      events were primarily mediated by activation of the Prostaglandin (PG) E receptor
      EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could
      mitigate all of these events tested with cells in vitro as well as in vivo in
      syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice
      bearing COX-2 over-expressing human breast cancer xenografts. We suggest that
      EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors
      by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via
      EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced
      oncogenic and SLC-stimulating microRNAs-miR526b and miR655, one of which (miR655)
      appears to be a potential blood biomarker in breast cancer patients for
      monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will
      likely produce the highest benefit in aggressive breast cancers, such as COX-2
      expressing triple-negative breast cancers, when combined with other newer agents,
      such as inhibitors of programmed cell death (PD)-1 or PD-L1.

PMID- 29596311
TI  - The Effects of Isoflavone Supplementation Plus Combined Exercise on Lipid Levels,
      and Inflammatory and Oxidative Stress Markers in Postmenopausal Women.
AB  - This study tested the effect of isoflavone supplementation in addition to
      combined exercise training on plasma lipid levels, inflammatory markers and
      oxidative stress in postmenopausal women. Thirty-two healthy and non-obese
      postmenopausal women without hormone therapy were randomly assigned to exercise +
      placebo (PLA; n = 15) or exercise + isoflavone supplementation (ISO; n = 17)
      groups. They performed 30 sessions of combined exercises (aerobic plus
      resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or
      placebo. Blood samples were collected after an overnight fast to analyze the
      lipid profile, interleukin-6 (IL-6), interleukin-8 (IL-8), superoxide dismutase
      (SOD), total antioxidant capacity (FRAP), and thiobarbituric acid reactive
      substances (TBARS), before and after ten weeks of the intervention. There were no
      differences in the changes (pre vs. post) between groups for any of the
      inflammatory markers, oxidative stress markers or lipid profile variables.
      However, interleukin-8 was different between pre- and post-tests (p < 0.001) in
      both groups (&Delta; = 7.61 and 5.61 pg/mL) as were cholesterol levels (p <
      0.05), with no interaction between groups. The combination of isoflavone
      supplementation and exercise training did not alter oxidative stress markers in
      postmenopausal women, but exercise training alone may increase IL-8 and decrease
      total cholesterol levels.

PMID- 29596312
TI  - Physical Activity as a Determinant of Quality of Life in Working-Age People in
      Wroclaw, Poland.
AB  - Regular physical activity can greatly contribute to the improvement of physical
      fitness and performance, reduction of the incidence risk of some occupational
      diseases, and as a consequence, to a general improvement of quality of life in
      terms of health status. The aim of the article was to assess relationships
      between the quality of life and physical activity of a working-age population.
      The study material comprised 4460 residents of the city of Wroclaw, Poland (2129
      men, 2331 women) aged 18-64 years. The study was a questionnaire survey using the
      International Physical Activity Questionnaire Short Form (IPAQ-SF) and The World
      Health Organization Quality of Life (WHOQOL-BREF) questionnaires. The highest
      levels of overall quality of life and its four particular domains (physical,
      psychological, social, and environmental), as well as perceived health conditions
      were found among the most physically active respondents. Furthermore, the odds of
      high assessment of perceived overall quality of life were shown to increase with
      the increasing levels of physical activity. Activities aimed at the improvement
      of the quality of life of working-age people should involve programs enhancing
      the development of physical activity.

PMID- 29596313
TI  - Relationship between Nutritional Status and Gastrointestinal Symptoms in
      Geriatric Patients with End-Stage Renal Disease on Dialysis.
AB  - Gastrointestinal symptoms (GIS) are common in patients with end-stage renal
      disease (ESRD) and are associated with nutritional risks resulting from low food
      intake. Little is known about the relationship between GIS and malnutrition in
      geriatric patients with ESRD. The main objective of this study was to determine
      the relationship between nutritional status and severity of GIS in geriatric
      patients on dialysis therapy. Clinically-stable geriatric patients (older than 60
      years old) who were dialysis outpatients were included in this cross-sectional
      study. The severity of GIS was assessed using the Gastrointestinal Symptoms
      Questionnaire (GSQ, short version), with patients classified into three groups:
      mild, moderate, and severe. Nutritional status was evaluated with the
      Malnutrition Inflammation Score (MIS), anthropometric assessment, biochemical
      parameters, and bioelectrical impedance. Descriptive statistics were used and
      differences between groups were analyzed with ANOVA and Kruskal Wallis, with a p
      < 0.05 considered to indicate significance. Fifty patients completed the study;
      the median age was 67 years old. Twenty-three patients were on hemodialysis (HD)
      and 27 were on peritoneal dialysis (PD). No significant differences were found
      according to dialysis modality, presence of diabetes, or gender. Ninety percent
      of patients had at least one GIS. Poorer nutritional status (evaluated by MIS)
      was related to a higher severity of GIS. There were no significant differences
      with other nutritional parameters. Our study showed a high prevalence of GIS in
      geriatric patients. There were no differences in observed GIS values that were
      attributed to dialysis modality, gender, or presence of type 2 diabetes mellitus
      (DM2). Severe GIS values were associated with poorer nutritional status
      determined by MIS, however, there was no association with anthropometry,
      biochemical values, or bioimpedance vector analysis.

PMID- 29596314
TI  - Betaine in Cereal Grains and Grain-Based Products.
AB  - Betaine is a non-essential nutrient which performs several important
      physiological functions in organisms. Abundant data exist to suggest that betaine
      has a potential for prevention of chronic diseases and that its dietary intake
      may contribute to overall health enhancement. Several studies have pointed out
      that the betaine status of the general population is inadequate and have
      suggested nutritional strategies to improve dietary intake of betaine. Cereal
      based food has been implicated as the major source of betaine in the Western
      diet. This review summarizes the results on the betaine content in various
      cereals and related products. Attention has been given to the betaine content in
      gluten-free grains and products. It also discusses the stability of betaine
      during processing (cooking, baking, extrusion) and possibilities to increase
      betaine content by fortification.

PMID- 29596315
TI  - Core Level Spectra of Organic Molecules Adsorbed on Graphene.
AB  - We perform first principle calculations based on density functional theory to
      investigate the effect of the adsorption of core-excited organic molecules on
      graphene. We simulate Near Edge X-ray absorption Fine Structure (NEXAFS) and X
      ray Photoemission Spectroscopy (XPS) at the N and C edges for two moieties:
      pyridine and the pyridine radical on graphene, which exemplify two different
      adsorption characters. The modifications of molecular and graphene energy levels
      due to their interplay with the core-level excitation are discussed. We find that
      upon physisorption of pyridine, the binding energies of graphene close to the
      adsorption site reduce mildly, and the NEXAFS spectra of the molecule and
      graphene resemble those of gas phase pyridine and pristine graphene,
      respectively. However, the chemisorption of the pyridine radical is found to
      significantly alter these core excited spectra. The C 1s binding energy of the C
      atom of graphene participating in chemisorption increases by ~1 eV, and the C
      atoms of graphene alternate to the adsorption site show a reduction in the
      binding energy. Analogously, these C atoms also show strong modifications in the
      NEXAFS spectra. The NEXAFS spectrum of the chemisorbed molecule is also modified
      as a result of hybridization with and screening by graphene. We eventually
      explore the electronic properties and magnetism of the system as a core-level
      excitation is adiabatically switched on.

PMID- 29596316
TI  - Review on PACAP-Induced Transcriptomic and Proteomic Changes in Neuronal
      Development and Repair.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with
      widespread occurrence and diverse biological effects. Among its several different
      effects, of special importance is the action of PACAP on neuronal proliferation,
      differentiation and migration, and neuroprotection. The neuroprotective mechanism
      of PACAP is both direct and indirect, via neuronal and non-neuronal cells.
      Several research groups have performed transcriptomic and proteomic analysis on
      PACAP-mediated genes and proteins. Hundreds of proteins have been described as
      being involved in the PACAP-mediated neuroprotection. In the present review we
      summarize the few currently available transcriptomic data potentially leading to
      the proteomic changes in neuronal development and protection. Proteomic studies
      focusing on the neuroprotective role of PACAP are also reviewed and discussed in
      light of the most intriguing and promising effect of this neuropeptide, which may
      possibly have future therapeutic potential.

PMID- 29596318
TI  - Dietary Cholesterol, Serum Lipids, and Heart Disease: Are Eggs Working for or
      Against You?
AB  - The relationship between blood cholesterol and heart disease is well-established,
      with the lowering of serum low-density lipoprotein (LDL)-cholesterol being the
      primary target of preventive therapy. Furthermore, epidemiological studies report
      lower risk for heart disease with higher concentrations of high-density
      lipoprotein (HDL)-cholesterol. There has also been considerable interest in
      studying the relationship between dietary cholesterol intake and heart disease
      risk. Eggs are one of the richest sources of cholesterol in the diet. However,
      large-scale epidemiological studies have found only tenuous associations between
      the intake of eggs and cardiovascular disease risk. Well-controlled, clinical
      studies show the impact of dietary cholesterol challenges via egg intake on serum
      lipids is highly variable, with the majority of individuals (~2/3 of the
      population) having only minimal responses, while those with a significant
      response increase both LDL and HDL-cholesterol, typically with a maintenance of
      the LDL/HDL cholesterol ratio. Recent drug trials targeting HDL-cholesterol have
      been unsuccessful in reducing cardiovascular events, and thus it is unclear if
      raising HDL-cholesterol with chronic egg intake is beneficial. Other important
      changes with egg intake include potentially favorable effects on lipoprotein
      particle profiles and enhancing HDL function. Overall, the increased HDL
      cholesterol commonly observed with dietary cholesterol feeding in humans appears
      to also coincide with improvements in other markers of HDL function. However,
      more investigation into the effects of dietary cholesterol on HDL functionality
      in humans is warranted. There are other factors found in eggs that may influence
      risk for heart disease by reducing serum lipids, such as phospholipids, and these
      may also modify the response to dietary cholesterol found in eggs. In this
      review, we discuss how eggs and dietary cholesterol affect serum cholesterol
      concentrations, as well as more advanced lipoprotein measures, such as
      lipoprotein particle profiles and HDL metabolism.

PMID- 29596317
TI  - Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas
      and Their Role as a Drug Delivery System for Doxorubicin-Preclinical Studies in a
      Murine Model.
AB  - Feline injection site sarcomas (FISS) are malignant skin tumors with high
      recurrence rates despite the primary treatment of radical surgical resections.
      Adjunctive radiotherapy or chemotherapy with doxorubicin is mostly ineffective.
      Cellular and molecular causes of multidrug resistance, specific physio-chemical
      properties of solid tumors impairing drug transport, and the tumor
      microenvironment have been indicated for causing standard chemotherapy failure.
      Gold nanoparticles are promising imaging tools, nanotherapeutics, and drug
      delivery systems (DDS) for chemotherapeutics, improving drug transport within
      solid tumors. This study was conducted to assess the distribution of 4-nm
      glutathione-stabilized gold nanoparticles in FISS and their influence on kidney
      and liver parameters in nude mice. The role of gold nanoparticles as a
      doxorubicin DDS in FISS was examined to determine the potential reasons for
      failure to translate results from in vitro to in vivo studies. Grade III tumors
      characterized by a large area of necrosis at their core displayed positive
      immuneexpression of tumor-associated macrophages (TAM) at both the periphery and
      within the tumor core near the area of necrosis. Gold nanoparticles did not cause
      necrosis at the injection site and had no negative effect on liver and kidney
      parameters in nude mice. Gold nanoparticles accumulated in the tumor core and at
      the periphery and co-internalized with TAM-an important observation and potential
      therapeutic target warranting further investigation. The large area of necrosis
      and high immunoexpression of TAM, indicating "pro-tumor macrophages", may be
      responsible for FISS tumor progression and therapeutic failure. However, further
      studies are required to test this hypothesis.

PMID- 29596319
TI  - Enrichment of Probiotic Fermented Milk with Green Banana Pulp: Characterization
      Microbiological, Physicochemical and Sensory.
AB  - The aims of this study were (i) to evaluate the growth kinetic of L. paracasei
      LBC 81 in fermented milks enriched with green banana pulp (GBP); (ii) to evaluate
      the effect of the incorporation of GBP on the chemical composition and the
      sensory acceptance; and (iii) to study the viability of the probiotic and
      technological properties during refrigerated storage. The amount of GBP used were
      3.0, 6.0 and 9.0 g/100 g. The results show that the higher the concentration of
      GBP added, the shorter the time taken to reach pH 4.6. It was observed that the
      incorporation of GBP did not affect negatively the viability of L. paracasei LBC
      81 during storage. The fermented milk elaborated with 6.0 g/100 g of GBP was the
      most accepted. The present study indicates that the enrichment of fermented milk
      with GBP favors the stability of the probiotic strain, L. paracasei LBC 81 during
      storage.

PMID- 29596320
TI  - A Review of Selective Laser Melted NiTi Shape Memory Alloy.
AB  - NiTi shape memory alloys (SMAs) have the best combination of properties among the
      different SMAs. However, the limitations of conventional manufacturing processes
      and the poor manufacturability of NiTi have critically limited its full potential
      applicability. Thus, additive manufacturing, commonly known as 3D printing, has
      the potential to be a solution in fabricating complex NiTi smart structures.
      Recently, a number of studies on Selective Laser Melting (SLM) of NiTi were
      conducted to explore the various aspects of SLM-produced NiTi. Compared to
      producing conventional metals through the SLM process, the fabrication of NiTi
      SMA is much more challenging. Not only do the produced parts require a high
      density that leads to good mechanical properties, strict composition control is
      needed as well for the SLM NiTi to possess suitable phase transformation
      characteristics. Additionally, obtaining a good shape memory effect from the SLM
      NiTi samples is another challenging task that requires further understanding.
      This paper presents the results of the effects of energy density and SLM process
      parameters on the properties of SLM NiTi. Its shape memory properties and
      potential applications were then reviewed and discussed.

PMID- 29596321
TI  - Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed
      Perinatally to 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47).
AB  - For the majority of lipophilic compounds, adipose tissue is traditionally
      considered as a storage depot and only rarely as a target organ. Meanwhile,
      abnormalities in adipose tissue physiology induced by chemical exposure may
      contribute to the current epidemic of obesity and metabolic diseases.
      Polybrominated diphenyl ethers (PBDEs) are a group of lipophilic flame retardants
      found in the majority of human samples in North America. Their ability to alter
      the physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2
      mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal
      adipose tissue were analyzed in male offspring using the RNA-seq approach with
      subsequent bioinformatic analysis. The expression of genes of coagulation and
      complement cascade, de novo lipogenesis, and xenobiotic metabolism was altered in
      response to BDE-47 exposure. The affected molecular network included the
      following hubs: PPARalpha, HNF1A, and HNF4. These findings suggest that adipose
      tissue should be considered a target tissue for BDE-47, in addition to its role
      as a storage depot. This study also builds a background for a targeted search of
      sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile
      parameters and coagulation factors in circulation. Additional studies are needed
      to investigate the role of PBDEs as an obesogen.

PMID- 29596322
TI  - Development of Polyclonal Antibody against Clenbuterol for Immunoassay
      Application.
AB  - Development of an immunoassay for clenbuterol (CLB) detection required an anti
      CLB antibody as an important bioreceptor. In this study, we report our work on
      production and purification of a rabbit-derived polyclonal anti-CLB antibody. The
      antibody was then purified by nProtein A Sepharose affinity column and the
      antibody purity was confirmed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis. The activities of purified antibody were
      evaluated based on high antibody titer determined from enzyme-linked
      immunosorbent assay (ELISA). The sensitivity and selectivity of this antibody was
      evaluated and exhibits negligible cross-reactivity to antibiotics other than beta
      agonist families. Evaluation of the antibody as bioreceptor in immunoassay was
      performed using direct competitive ELISA and exhibited linear calibration plot
      (R2 = 0.9484). The antibody was used to detect the content of CLB in spiked milk
      samples and the recovery of more than 92% indicating significant performance as
      bioreceptor for the development of a rapid and simple immunoassay.

PMID- 29596323
TI  - Biofunctionalized Scaffold in Bone Tissue Repair.
AB  - Bone tissue engineering is based on bone grafting to repair bone defects. Bone
      graft substitutes can contribute to the addition of mesenchymal stem cells (MSCs)
      in order to enhance the rate and the quality of defect regeneration. The stem
      cell secretome contains many growth factors and chemokines, which could affect
      cellular characteristics and behavior. Conditioned medium (CM) could be used in
      tissue regeneration avoiding several problems linked to the direct use of MSCs.
      In this study, we investigated the effect of human periodontal ligament stem
      cells (hPDLSCs) and their CM on bone regeneration using a commercially available
      membrane scaffold Evolution (EVO) implanted in rat calvarias. EVO alone or EVO +
      hPDLSCs with or without CM were implanted in Wistar male rats subjected to
      calvarial defects. The in vivo results revealed that EVO membrane enriched with
      hPDLSCs and CM showed a better osteogenic ability to repair the calvarial defect.
      These results were confirmed by acquired micro-computed tomography (CT) images
      and the increased osteopontin levels. Moreover, RT-PCR in vitro revealed the
      upregulation of three genes (Collagen (COL)5A1, COL16A1 and transforming growth
      factor (TGF)beta1) and the down regulation of 26 genes involved in bone
      regeneration. These results suggest a promising potential application of CM from
      hPDLSCs and scaffolds for bone defect restoration and in particular for calvarial
      repair in case of trauma.

PMID- 29596324
TI  - Camelid Single-Domain Antibodies (VHHs) against Crotoxin: A Basis for Developing
      Modular Building Blocks for the Enhancement of Treatment or Diagnosis of Crotalic
      Envenoming.
AB  - Toxic effects triggered by crotalic envenoming are mainly related to crotoxin
      (CTX), composed of a phospholipase A2 (CB) and a subunit with no toxic activity
      (CA). Camelids produce immunoglobulins G devoid of light chains, in which the
      antigen recognition domain is called VHH. Given their unique characteristics,
      VHHs were selected using Phage Display against CTX from Crotalus durissus
      terrificus. After three rounds of biopanning, four sequence profiles for CB
      (KF498602, KF498603, KF498604, and KF498605) and one for CA (KF498606) were
      revealed. All clones presented the VHH hallmark in FR2 and a long CDR3, with the
      exception of KF498606. After expressing pET22b-VHHs in E. coli, approximately 2
      to 6 mg of protein per liter of culture were obtained. When tested for cross
      reactivity, VHHs presented specificity for the Crotalus genus and were capable of
      recognizing CB through Western blot. KF498602 and KF498604 showed
      thermostability, and displayed affinity constants for CTX in the micro or
      nanomolar range. They inhibited in vitro CTX PLA2 activity, and CB cytotoxicity.
      Furthermore, KF498604 inhibited the CTX-induced myotoxicity in mice by 78.8%.
      Molecular docking revealed that KF498604 interacts with the CA&ndash;CB interface
      of CTX, seeming to block substrate access. Selected VHHs may be alternatives for
      the crotalic envenoming treatment.

PMID- 29596325
TI  - Preconditioning-Like Properties of Short-Term Hypothermia in Isolated Perfused
      Rat Liver (IPRL) System.
AB  - Hypothermia may attenuate the progression of ischemia-induced damage in liver.
      Here, we determined the effects of a brief cycle of hypothermic preconditioning
      applied before an ischemic/reperfusion (I/R) episode in isolated perfused rat
      liver (IPRL) on tissue damage and oxidative stress. Rats (male, 200-250 g) were
      anaesthetised with sodium pentobarbital (60 mg.kg-1 i.p) and underwent
      laparatomy. The liver was removed and perfused in a temperature-regulated non
      recirculating system. Livers were randomly divided into two groups (n = 6 each
      group). In the hypothermia-preconditioned group, livers were perfused with
      hypothermic buffer (cycle of 10 min at 22  degrees C plus 10 min at 37  degrees
      C) and the other group was perfused at 37  degrees C. Both groups were then
      submitted to 40 min of warm ischemia and 20 min of warm reperfusion. The level of
      tissue-damage indicators (alanine amino transferase, ALT; lactate dehydrogenase,
      LDH; and proteins), oxidative stress markers (thiobarbituric acid-reactive
      substances, TBARS; advanced oxidation protein products, AOPP; and glutathione,
      GSH) were measured in aliquots of perfusate sampled at different time intervals.
      Histological determinations and oxidative stress biomarkers in homogenized liver
      (AOPP; TBARS; nitric oxide derivatives, NOx; GSH and glutathione disulphide,
      GSSG) were also made in the tissue at the end. Results showed that both damage
      and oxidant indicators significantly decreased while antioxidant increased in
      hypothermic preconditioned livers. In addition, homogenized liver determinations
      and histological observations at the end of the protocol corroborate the results
      in the perfusate, confirming the utility of the perfusate as a non-invasive
      method. In conclusion, hypothermic preconditioning attenuates oxidative damage
      and appears to be a promising strategy to protect the liver against IR injury.

PMID- 29596326
TI  - Differentiation Therapy Targeting the beta-Catenin/CBP Interaction in Pancreatic
      Cancer.
AB  - BACKGROUND: Although canonical Wnt signaling is known to promote tumorigenesis in
      pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K
      Ras, the detailed molecular mechanisms by which the Wnt effector beta-catenin
      regulates such tumorigenesis are largely unknown. We have previously demonstrated
      that beta-catenin's differential usage of the Kat3 transcriptional coactivator
      cyclic AMP-response element binding protein-binding protein (CBP) over its highly
      homologous coactivator p300 increases self-renewal and suppresses differentiation
      in other types of cancer. AIM/METHODS: To investigate Wnt-mediated carcinogenesis
      in PDAC, we have used the specific small molecule CBP/beta-catenin antagonist,
      ICG-001, which our lab identified and has extensively characterized, to examine
      its effects in human pancreatic cancer cells and in both an orthotopic mouse
      model and a human patient-derived xenograft (PDX) model of PDAC.
      RESULTS/CONCLUSION: We report for the first time that K-Ras activation increases
      the CBP/beta-catenin interaction in pancreatic cancer; and that ICG-001 specific
      antagonism of the CBP/beta-catenin interaction sensitizes pancreatic cancer cells
      and tumors to gemcitabine treatment. These effects were associated with increases
      in the expression of let-7a microRNA; suppression of K-Ras and survivin; and the
      elimination of drug-resistant cancer stem/tumor-initiating cells.

PMID- 29596328
TI  - Performance of the Adult ADHD Self-Report Scale-v1.1 in Adults with Major
      Depressive Disorder.
AB  - Attention deficit/hyperactivity disorder (ADHD) is an under-recognized comorbid
      disorder among patients with mood disorders. ADHD is an independent risk factor
      for suicidal ideation and behavior and contributes to many aspects of impaired
      function in adults. Diagnosis of ADHD in Major Depressive Disorder (MDD) patients
      is challenging due to the overlap in cognitive symptoms between the two
      disorders. The ADHD Self-Report Scale, version 1.1 (ASRS-v1.1) is a widely used
      screening instrument for ADHD in adults but its accuracy has not been evaluated
      previously in treatment-seeking MDD patients. We administered the ASRS-v1.1 to 55
      healthy controls and 40 adults with a primary psychiatric diagnosis of MDD who
      were participating in clinical research studies. ADHD diagnosis was assessed via
      structured interview with the adult ADHD module of the Mini International
      Neuropsychiatric Interview Plus version 6.0.0 (MINI) along with a psychiatrist's
      assessment. Overall, full-syndrome ADHD was diagnosed in 12.5% of the MDD
      patients. MDD patients endorsed all 18 items of the ASRS-v1.1 more frequently
      than the healthy controls and the number of ASRS-v1.1 items endorsed correlated
      with levels of anxiety in the MDD patients. The ASRS-v1.1 demonstrated fair
      performance for identifying full syndrome DSM-IV ADHD diagnosis, with sensitivity
      60%, specificity: 68.6%, positive predictive value 21.4%, negative predictive
      value 92.3% and total classification accuracy of 67.5%. Positive predictive value
      improved substantially when the ADHD criterion requiring symptom onset before age
      7 was omitted. In adult MDD patients, a negative ASRS-v1.1 screen strongly
      suggests the absence of ADHD but positive screen results require careful
      evaluation to determine whether self-reported ADHD symptoms simply emerge from
      depression or whether comorbid ADHD is present.

PMID- 29596327
TI  - Disruption of PTPS Gene Causing Pale Body Color and Lethal Phenotype in the
      Silkworm, Bombyx mori.
AB  - Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the
      phenylalanine hydroxylase (PAH) gene or by defects in the tetrahydrobiopterin
      (BH4) synthesis pathway. Here, by positional cloning, we report that the 6
      pyruvoyl-tetrahydropterin synthase (PTPS) gene, encoding a key enzyme of BH4
      biosynthesis, is responsible for the alc (albino C) mutation that displays pale
      body color, head shaking, and eventually lethality after the first molting in
      silkworm. Compared to wild type, the alc mutant produced more substrates
      (phenylalanine (Phe) and tyrosine (Tyr)) and generated less DOPA and dopamine.
      Application of 2,4-diamino-6-hydroxypyrimidine (DAHP) to block BH4 synthesis in
      the wild type effectively produced the alc-like phenotype, while BH4
      supplementation rescued the defective body color and lethal phenotype in both alc
      and DAHP-treated individuals. The detection of gene expressions and metabolic
      substances after drugs treatments in alc and normal individuals imply that
      silkworms and humans have a high similarity in the drugs metabolic features and
      the gene pathway related to BH4 and the dopamine biosynthesis. We propose that
      the alc mutant could be used as an animal model for drug evaluation for BH4
      deficient PKU.

PMID- 29596329
TI  - Crystal Structure of CYP2B6 in Complex with an Efavirenz Analog.
AB  - The over two dozen CYP2B structures of human, rabbit, and woodrat enzymes solved
      in the last decade have significantly enhanced our understanding of the structure
      function relationships of drug metabolizing enzymes. More recently, an important
      role has emerged for halogen-pi interactions in the CYP2B6 active site in
      substrate selectivity, explaining in part the preference for halogenated ligands
      as substrates. The mechanism by which such ligands interact with CYP2B enzymes
      involves conserved phenylalanine side chains, in particular F108, F115, or F297,
      in the active site, which form pi bonds with halogens. To illustrate such halogen
      pi interactions using drugs that are major substrates of CYP2B6, we present here
      a crystal structure of CYP2B6 in complex with an analog of the widely used anti
      HIV drug efavirenz, which contains a methyl group in place of the carbonyl
      oxygen. The chlorine of the efavirenz analog forms a pi bond with the aromatic
      ring of F108, whereas the putative metabolism site on the distal end of the
      molecule is oriented towards the heme iron. The crystal structure showcases how
      CYP2B6 accommodates this important drug analog of considerable size in the active
      site by movement of various side chains without substantially increasing the
      active site volume. Furthermore, the CYP2B6-efavirenz analog complex provides a
      useful platform to investigate computationally as well as biophysically the
      effect of genetic polymorphisms on binding of the widely studied efavirenz.

PMID- 29596330
TI  - Modeling and Assessment of Precise Time Transfer by Using BeiDou Navigation
      Satellite System Triple-Frequency Signals.
AB  - This study proposes two models for precise time transfer using the BeiDou
      Navigation Satellite System triple-frequency signals: ionosphere-free (IF)
      combined precise point positioning (PPP) model with two dual-frequency
      combinations (IF-PPP1) and ionosphere-free combined PPP model with a single
      triple-frequency combination (IF-PPP2). A dataset with a short baseline (with a
      common external time frequency) and a long baseline are used for performance
      assessments. The results show that IF-PPP1 and IF-PPP2 models can both be used
      for precise time transfer using BeiDou Navigation Satellite System (BDS) triple
      frequency signals, and the accuracy and stability of time transfer is the same in
      both cases, except for a constant system bias caused by the hardware delay of
      different frequencies, which can be removed by the parameter estimation and
      prediction with long time datasets or by a priori calibration.

PMID- 29596331
TI  - Effect of Vertical Annealing on the Nitrogen Dioxide Response of Organic Thin
      Film Transistors.
AB  - Nitrogen dioxide (NO2) sensors based on organic thin-film transistors (OTFTs)
      were fabricated by conventional annealing (horizontal) and vertical annealing
      processes of organic semiconductor (OSC) films. The NO2 responsivity of OTFTs to
      15 ppm of NO2 is 1408% under conditions of vertical annealing and only 72% when
      conventional annealing is applied. Moreover, gas sensors obtained by vertical
      annealing achieve a high sensing performance of 589% already at 1 ppm of NO2,
      while showing a preferential response to NO2 compared with SO2, NH3, CO, and H2S.
      To analyze the mechanism of performance improvement of OTFT gas sensors, the
      morphologies of 6,13-bis(triisopropylsilylethynyl)-pentacene (TIPS-pentacene)
      films were characterized by atomic force microscopy (AFM) in tapping mode. The
      results show that, in well-aligned TIPS-pentacene films, a large number of
      effective grain boundaries inside the conducting channel contribute to the
      enhancement of NO2 gas sensing performance.

PMID- 29596332
TI  - Semi-Automated Air-Coupled Impact-Echo Method for Large-Scale Parkade Structure.
AB  - Structural Health Monitoring (SHM) has moved to data-dense systems, utilizing
      numerous sensor types to monitor infrastructure, such as bridges and dams, more
      regularly. One of the issues faced in this endeavour is the scale of the
      inspected structures and the time it takes to carry out testing. Installing
      automated systems that can provide measurements in a timely manner is one way of
      overcoming these obstacles. This study proposes an Artificial Neural Network
      (ANN) application that determines intact and damaged locations from a small
      training sample of impact-echo data, using air-coupled microphones from a
      reinforced concrete beam in lab conditions and data collected from a field
      experiment in a parking garage. The impact-echo testing in the field is carried
      out in a semi-autonomous manner to expedite the front end of the in situ damage
      detection testing. The use of an ANN removes the need for a user-defined cutoff
      value for the classification of intact and damaged locations when a least-square
      distance approach is used. It is postulated that this may contribute
      significantly to testing time reduction when monitoring large-scale civil
      Reinforced Concrete (RC) structures.

PMID- 29596333
TI  - Patient as a Partner in Healthcare-Associated Infection Prevention.
AB  - OBJECTIVES: The objective of the study was getting to know the knowledge and
      attitudes towards hand hygiene (HH) among Polish patients and healthcare workers
      (HCWs). METHODS: 459 respondents replied to the survey: 173 (37.6%) patients and
      286 (62.3%) HCWs; 57 HCWs were additionally interviewed. RESULTS: Few HCWs knew
      and used the "5 moments for HH" in the required situations. Both patients and
      HCWs rated HH of other HCWs poorly: only 75% of patients and 54% of HCWs noticed
      the application of HH before blood sample collection, but 1/2 of interviewed HCWs
      did not encounter a request for HH from a patient. According to interviews, 23
      (40%) HCWs did not admonish others when they did not use HH. Seventy-five percent
      of patients and HCWs claimed that, in the past, in schools the toilets were
      poorly stocked, but the situation improved with the passage of time. CONCLUSIONS:
      There are barriers with resspect to treating patients as partners in HH in Polish
      hospitals and HCWs' lack of compliance with the "5 moments for HH" significantly
      reduces patients' safety. PRACTICE IMPLICATIONS: Education regarding HH should be
      conducted for the whole society from an early age: lack of proper supplies in
      school bathrooms impedes the development of positive HH habits.

PMID- 29596335
TI  - Poisson-Gaussian Noise Analysis and Estimation for Low-Dose X-ray Images in the
      NSCT Domain.
AB  - The noise distribution of images obtained by X-ray sensors in low-dosage
      situations can be analyzed using the Poisson and Gaussian mixture model.
      Multiscale conversion is one of the most popular noise reduction methods used in
      recent years. Estimation of the noise distribution of each subband in the
      multiscale domain is the most important factor in performing noise reduction,
      with non-subsampled contourlet transform (NSCT) representing an effective method
      for scale and direction decomposition. In this study, we use artificially
      generated noise to analyze and estimate the Poisson-Gaussian noise of low-dose X
      ray images in the NSCT domain. The noise distribution of the subband coefficients
      is analyzed using the noiseless low-band coefficients and the variance of the
      noisy subband coefficients. The noise-after-transform also follows a Poisson
      Gaussian distribution, and the relationship between the noise parameters of the
      subband and the full-band image is identified. We then analyze noise of actual
      images to validate the theoretical analysis. Comparison of the proposed noise
      estimation method with an existing noise reduction method confirms that the
      proposed method outperforms traditional methods.

PMID- 29596336
TI  - An Effective Hybrid Routing Algorithm in WSN: Ant Colony Optimization in
      combination with Hop Count Minimization.
AB  - Low cost, high reliability and easy maintenance are key criteria in the design of
      routing protocols for wireless sensor networks (WSNs). This paper investigates
      the existing ant colony optimization (ACO)-based WSN routing algorithms and the
      minimum hop count WSN routing algorithms by reviewing their strengths and
      weaknesses. We also consider the critical factors of WSNs, such as energy
      constraint of sensor nodes, network load balancing and dynamic network topology.
      Then we propose a hybrid routing algorithm that integrates ACO and a minimum hop
      count scheme. The proposed algorithm is able to find the optimal routing path
      with minimal total energy consumption and balanced energy consumption on each
      node. The algorithm has unique superiority in terms of searching for the optimal
      path, balancing the network load and the network topology maintenance. The WSN
      model and the proposed algorithm have been implemented using C++. Extensive
      simulation experimental results have shown that our algorithm outperforms several
      other WSN routing algorithms on such aspects that include the rate of
      convergence, the success rate in searching for global optimal solution, and the
      network lifetime.

PMID- 29596334
TI  - Tackling HIV Persistence: Pharmacological versus CRISPR-Based Shock Strategies.
AB  - Jan Svoboda studied aspects of viral latency, in particular with respect to
      disease induction by avian RNA tumor viruses, which were later renamed as part of
      the extended retrovirus family. The course of retroviral pathogenesis is
      intrinsically linked to their unique property of integrating the DNA copy of the
      retroviral genome into that of the host cell, thus forming the provirus.
      Retroviral latency has recently become of major clinical interest to allow a
      better understanding of why we can effectively block the human immunodeficiency
      virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never
      reach a cure. We will discuss HIV-1 latency and its direct consequence-the
      formation of long-lasting HIV-1 reservoirs. We next focus on one of the most
      explored strategies in tackling HIV-1 reservoirs-the "shock and kill" strategy
      which describes the broadly explored pharmacological way of kicking the latent
      provirus, with subsequent killing of the virus-producing cell by the immune
      system. We furthermore present how the clustered regularly interspaced
      palindromic repeats (CRISPR) and associated protein (Cas) system can be harnessed
      to reach the same objective by reactivating HIV-1 gene expression from latency.
      We will review the benefits and drawbacks of these different cure strategies.

PMID- 29596337
TI  - A Comparison of Inductive Sensors in the Characterization of Partial Discharges
      and Electrical Noise Using the Chromatic Technique.
AB  - Partial discharges (PDs) are one of the most important classes of ageing
      processes that occur within electrical insulation. PD detection is a standardized
      technique to qualify the state of the insulation in electric assets such as
      machines and power cables. Generally, the classical phase-resolved partial
      discharge (PRPD) patterns are used to perform the identification of the type of
      PD source when they are related to a specific degradation process and when the
      electrical noise level is low compared to the magnitudes of the PD signals.
      However, in practical applications such as measurements carried out in the field
      or in industrial environments, several PD sources and large noise signals are
      usually present simultaneously. In this study, three different inductive sensors
      have been used to evaluate and compare their performance in the detection and
      separation of multiple PD sources by applying the chromatic technique to each of
      the measured signals.

PMID- 29596338
TI  - Non-Invasive Electromagnetic Skin Patch Sensor to Measure Intracranial Fluid
      Volume Shifts.
AB  - Elevated intracranial fluid volume can drive intracranial pressure increases,
      which can potentially result in numerous neurological complications or death.
      This study's focus was to develop a passive skin patch sensor for the head that
      would non-invasively measure cranial fluid volume shifts. The sensor consists of
      a single baseline component configured into a rectangular planar spiral with a
      self-resonant frequency response when impinged upon by external radio frequency
      sweeps. Fluid volume changes (10 mL increments) were detected through cranial
      bone using the sensor on a dry human skull model. Preliminary human tests
      utilized two sensors to determine feasibility of detecting fluid volume shifts in
      the complex environment of the human body. The correlation between fluid volume
      changes and shifts in the first resonance frequency using the dry human skull was
      classified as a second order polynomial with R2 = 0.97. During preliminary and
      secondary human tests, a ~24 MHz and an average of ~45.07 MHz shifts in the
      principal resonant frequency were measured respectively, corresponding to the
      induced cephalad bio-fluid shifts. This electromagnetic resonant sensor may
      provide a non-invasive method to monitor shifts in fluid volume and assist with
      medical scenarios including stroke, cerebral hemorrhage, concussion, or
      monitoring intracranial pressure.

PMID- 29596339
TI  - Investigating Water Movement Within and Near Wells Using Active Point Heating and
      Fiber Optic Distributed Temperature Sensing.
AB  - There are few methods to provide high-resolution in-situ characterization of flow
      in aquifers and reservoirs. We present a method that has the potential to
      quantify lateral and vertical (magnitude and direction) components of flow with
      spatial resolution of about one meter and temporal resolution of about one day. A
      fiber optic distributed temperature sensor is used with a novel heating system.
      Temperatures before heating may be used to evaluate background geothermal
      gradient and vertical profile of thermal diffusivity. The innovation presented is
      the use of variable energy application along the well, in this case concentrated
      heating at equally-spaced (2 m) localized areas (0.5 m). Relative to uniform
      warming this offers greater opportunity to estimate water movement, reduces
      required heating power, and increases practical length that can be heated.
      Numerical simulations are presented which illustrate expected behaviors. We
      estimate relative advection rates near the well using the times at which various
      locations diverge from a heating trajectory expected for pure conduction in the
      absence of advection. The concept is demonstrated in a grouted 600 m borehole
      with 300 heated patches, though evidence of vertical water movement was not seen.

PMID- 29596340
TI  - Volterra Kernel Estimation of White Light LEDs in the Time Domain.
AB  - In this paper, we present a time domain method for extracting coefficients of
      nonlinear Volterra-series kernels for white light-emitting diodes (LED) used both
      for illumination and visible light communications. We show that this method may
      have several advantages over the thus far more popular frequency domain method.
      We successfully apply the measured kernel coefficients up to the 3rd order for
      the modeling of nonlinear distortion impact on advanced modulation formats: pulse
      amplitude modulation, carrierless amplitude phase and orthogonal frequency
      division multiplexing. The impact of blue filtering on dynamic nonlinearity is
      also presented.

PMID- 29596341
TI  - Tunable Nanosensor Based on Fano Resonances Created by Changing the Deviation
      Angle of the Metal Core in a Plasmonic Cavity.
AB  - In this paper, a type of tunable plasmonic refractive index nanosensor based on
      Fano resonance is proposed and investigated. The sensor comprises a metal
      insulator-metal (MIM) nanocavity with a center-deviated metal core and two side
      coupled waveguides. By carefully adjusting the deviation angle and distance of
      the metal core in the cavity, Fano resonances can be obtained and modulated. The
      Fano resonances can be considered as results induced by the symmetry-breaking or
      geometric effect that affects the field distribution intensity at the coupling
      region between the right waveguide and the cavity. Such a field-distribution
      pattern change can be regarded as being caused by the interference between the
      waveguide modes and the cavity modes. The investigations demonstrate that the
      spectral positions and modulation depths of Fano resonances are highly sensitive
      to the deviation parameters. Furthermore, the figure of merit (FOM) value is
      calculated for different deviation angle. The result shows that this kind of
      tunable sensor has compact structure, high transmission, sharp Fano lineshape,
      and high sensitivity to the change in background refractive index. This work
      provides an effective method for flexibly tuning Fano resonance, which has wide
      applications in designing on-chip plasmonic nanosensors or other relevant
      devices, such as information modulators, optical filters, and ultra-fast
      switches.

PMID- 29596342
TI  - Statistical Platform for Individualized Behavioral Analyses Using Biophysical
      Micro-Movement Spikes.
AB  - Wearable biosensors, such as those embedded in smart phones, can provide data to
      assess neuro-motor control in mobile settings, at homes, schools, workplaces and
      clinics. However, because most machine learning algorithms currently used to
      analyze such data require several steps that depend on human heuristics, the
      analyses become computationally expensive and rather subjective. Further, there
      is no standardized scale or set of tasks amenable to take advantage of such
      technology in ways that permit broad dissemination and reproducibility of
      results. Indeed, there is a critical need for fully objective automated
      analytical methods that easily handle the deluge of data these sensors output,
      while providing standardized scales amenable to apply across large sections of
      the population, to help promote personalized-mobile medicine. Here we use an open
      access data set from Kaggle.com to illustrate the use of a new statistical
      platform and standardized data types applied to smart phone accelerometer and
      gyroscope data from 30 participants, performing six different activities. We
      report full distinction without confusion of the activities from the Kaggle set
      using a single parameter (linear acceleration or angular speed). We further
      extend the use of our platform to characterize data from commercially available
      smart shoes, using gait patterns within a set of experiments that probe nervous
      systems functioning and levels of motor control.

PMID- 29596344
TI  - Treatment of Arsenite Intoxication-Induced Peripheral Vasculopathy with
      Mesenchymal Stem Cells.
AB  - Arsenite (As), a notorious toxic metal, is ubiquitously distributed in the earth
      and poses a serious threat to human health. Histopathological lesions of As
      intoxication are known as thromboangiitis obliterans, which are resistant to
      current treatment and often lead to lower limb amputation. In this study, we
      attempt to find that treatment with mesenchymal stem cells (MSCs) may be
      effective for As-induced vasculopathy. We first conducted an in vitro study with
      a co-culture system containing human MSCs and human umbilical vein endothelial
      cells (HUVECs) and treated individual and co-cultured cells with various
      concentrations of arsenite. We also designed an in vivo study in which Sprague
      Dawley (SD) rats received periodic intraperitoneal (IP) injections of 16 ppm
      arsenite for 12 weeks. MSCs were harvested from BALB/c mice that were
      transplanted via tail vein injection. We found that there was significantly
      higher cellular viability in human mesenchymal stem cells (hMSCs) than in HUVECs
      under concentrations of arsenite between 15 and 25 MUM. The Annexin V apoptosis
      assay further confirmed this finding. Cytokine array assay for As-conditioned
      media revealed an elevated vascular endothelial growth factor (VEGF) level
      secreted by MSCs, which is crucial for HUVEC survival and was evaluated by an
      siRNA VEGF knockdown test. In the in vivo study, we demonstrated early apoptotic
      changes in the anterior tibial vessels of As-injected SD rats with a Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, but these
      apoptotic changes were less frequently observed upon MSCs transplantation,
      indicating that the cytoprotective effect of MSCs successfully protected against
      As-induced peripheral vasculopathy. The feasibility of MSCs to treat and /or
      prevent the progression of As-induced vasculopathy is justified. Further clinical
      studies are required to demonstrate the therapeutic efficacy of MSCs in patients
      suffering from As intoxication with vasculopathy.

PMID- 29596345
TI  - Farmers' Willingness to Pay for Health Risk Reductions of Pesticide Use in China:
      A Contingent Valuation Study.
AB  - This study aimed to estimate farmers' willingness to pay (WTP) for health risk
      reductions of pesticide use by applying the contingent valuation method (CVM) and
      to explore the factors that influence farmers' WTP in China. In total, 244
      farmers were randomly selected and interviewed. The mean WTP was estimated to be
      $65.38 (0.94% of total household income) per household per year for a 5/10,000
      reduction in morbidity risk. This study shows that farmers' socioeconomic and
      attitudinal factors that significantly affect their WTP include farmers' farming
      income, education, household size and risk perceptions. In particular, the
      results demonstrate that respondents' social trust, social reciprocity and social
      networks have significant impacts on their WTP. The findings of this study can
      provide useful insights for policy makers to design effective policies to address
      health problems related to pesticide use in the developing world.

PMID- 29596343
TI  - Antipruritic Effects of Botulinum Neurotoxins.
AB  - This review explores current evidence to demonstrate that botulinum neurotoxins
      (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in
      which botulinum neurotoxins have been applied for pruritus relief will be
      presented and significant findings will be highlighted. Potential mechanisms
      underlying antipruritic effects will also be discussed and ongoing challenges and
      unmet needs will be addressed.

PMID- 29596347
TI  - Health Impacts and Economic Costs of Air Pollution in the Metropolitan Area of
      Skopje.
AB  - BACKGROUND: Urban outdoor air pollution, especially particulate matter, remains a
      major environmental health problem in Skopje, the capital of the former Yugoslav
      Republic of Macedonia. Despite the documented high levels of pollution in the
      city, the published evidence on its health impacts is as yet scarce. METHODS: we
      obtained, cleaned, and validated Particulate Matter (PM) concentration data from
      five air quality monitoring stations in the Skopje metropolitan area, applied
      relevant concentration-response functions, and evaluated health impacts against
      two theoretical policy scenarios. We then calculated the burden of disease
      attributable to PM and calculated the societal cost due to attributable
      mortality. RESULTS: In 2012, long-term exposure to PM2.5 (49.2 MUg/m3) caused an
      estimated 1199 premature deaths (CI95% 821-1519). The social cost of the
      predicted premature mortality in 2012 due to air pollution was estimated at
      between 570 and 1470 million euros. Moreover, PM2.5 was also estimated to be
      responsible for 547 hospital admissions (CI95% 104-977) from cardiovascular
      diseases, and 937 admissions (CI95% 937-1869) for respiratory disease that year.
      Reducing PM2.5 levels to the EU limit (25 MUg/m3) could have averted an estimated
      45% of PM-attributable mortality, while achieving the WHO Air Quality Guidelines
      (10 MUg/m3) could have averted an estimated 77% of PM-attributable mortality.
      Both scenarios would also attain significant reductions in attributable
      respiratory and cardiovascular hospital admissions. CONCLUSIONS: Besides its
      health impacts in terms of increased premature mortality and hospitalizations,
      air pollution entails significant economic costs to the population of Skopje.
      Reductions in PM2.5 concentrations could provide substantial health and economic
      gains to the city.

PMID- 29596346
TI  - 1st German Phage Symposium-Conference Report.
AB  - In Germany, phage research and application can be traced back to the beginning of
      the 20th century. However, with the triumphal march of antibiotics around the
      world, the significance of bacteriophages faded in most countries, and respective
      research mainly focused on fundamental questions and niche applications. After a
      century, we pay tribute to the overuse of antibiotics that led to multidrug
      resistance and calls for new strategies to combat pathogenic microbes. Against
      this background, bacteriophages came into the spotlight of researchers and
      practitioners again resulting in a fast growing "phage community". In October
      2017, part of this community met at the 1st German Phage Symposium to share their
      knowledge and experiences. The participants discussed open questions and
      challenges related to phage therapy and the application of phages in general.
      This report summarizes the presentations given, highlights the main points of the
      round table discussion and concludes with an outlook for the different aspects of
      phage application.

PMID- 29596348
TI  - New Gene Markers for Metabolic Processes and Homeostasis in Porcine Buccal Pouch
      Mucosa during Cells Long Term-Cultivation-A Primary Culture Approach.
AB  - The oral mucosal tissue is a compound structure composed of morphologically and
      physiologically different cell types. The morphological modification involves
      genetically determined lifespan, which may be recognized as the balance between
      cell survival and apoptosis. Although the biochemical processes and pathways in
      oral mucosa, with special regards to drug transport, delivery, and metabolism,
      are well known, the cellular physiological homeostasis in this tissue requires
      further investigation. The porcine buccal pouch mucosal cells (BPMCs) collected
      from 20 pubertal crossbred Landrace gilts, were used in this study. Immediately
      after recovery, the oral mucosa was separated micro-surgically, and treated
      enzymatically. The dispersed cells were transferred into primary in vitro culture
      systems for a long-term cultivation of 30 days. After each step of in vitro
      culture (IVC), the cells were collected for isolation of total RNA at 24 h, 7,
      15, and 30 days of IVC. While the expression was analyzed for days 7, 15, and 30,
      the 24th hour was used as a reference for outcome calibration. The gene
      expression profile was determined using Affymetrix microarray assays and
      necessary procedures. In results, we observed significant up-regulation of
      SCARB1, PTGS2, DUSP5, ITGB3, PLK2, CCL2, TGFB1, CCL8, RFC4, LYN, ETS1, REL, LIF,
      SPP1, and FGER1G genes, belonging to two ontological groups, namely "positive
      regulation of metabolic process", and "regulation of homeostatic process" at 7
      day of IVC as compared to down-regulation at days 15 and 30. These findings
      suggest that the metabolic processes and homeostatic regulations are much more
      intense in porcine mucosal cells at day 7 of IVC. Moreover, the increased
      expression of marker genes, for both of these ontological groups, may suggest the
      existence of not only "morphological lifespan" during tissue keratinization, but
      also "physiological checkpoint" dedicated to metabolic processes in oral mucosa.
      This knowledge may be useful for preclinical experiments with drugs delivery and
      metabolism in both animals and humans.

PMID- 29596349
TI  - Genome-Wide Analyses of the NAC Transcription Factor Gene Family in Pepper
      (Capsicum annuum L.): Chromosome Location, Phylogeny, Structure, Expression
      Patterns, Cis-Elements in the Promoter, and Interaction Network.
AB  - The NAM, ATAF1/2, and CUC2 (NAC) transcription factors form a large plant
      specific gene family, which is involved in the regulation of tissue development
      in response to biotic and abiotic stress. To date, there have been no
      comprehensive studies investigating chromosomal location, gene structure, gene
      phylogeny, conserved motifs, or gene expression of NAC in pepper (Capsicum annuum
      L.). The recent release of the complete genome sequence of pepper allowed us to
      perform a genome-wide investigation of Capsicum annuum L. NAC (CaNAC) proteins.
      In the present study, a comprehensive analysis of the CaNAC gene family in pepper
      was performed, and a total of 104 CaNAC genes were identified. Genome mapping
      analysis revealed that CaNAC genes were enriched on four chromosomes (chromosomes
      1, 2, 3, and 6). In addition, phylogenetic analysis of the NAC domains from
      pepper, potato, Arabidopsis, and rice showed that CaNAC genes could be clustered
      into three groups (I, II, and III). Group III, which contained 24 CaNAC genes,
      was exclusive to the Solanaceae plant family. Gene structure and protein motif
      analyses showed that these genes were relatively conserved within each subgroup.
      The number of introns in CaNAC genes varied from 0 to 8, with 83 (78.9%) of CaNAC
      genes containing two or less introns. Promoter analysis confirmed that CaNAC
      genes are involved in pepper growth, development, and biotic or abiotic stress
      responses. Further, the expression of 22 selected CaNAC genes in response to
      seven different biotic and abiotic stresses [salt, heat shock, drought,
      Phytophthora capsici, abscisic acid, salicylic acid (SA), and methyl jasmonate
      (MeJA)] was evaluated by quantitative RT-PCR to determine their stress-related
      expression patterns. Several putative stress-responsive CaNAC genes, including
      CaNAC72 and CaNAC27, which are orthologs of the known stress-responsive
      Arabidopsis gene ANAC055 and potato gene StNAC30, respectively, were highly
      regulated by treatment with different types of stress. Our results also showed
      that CaNAC36 plays an important role in the interaction network, interacting with
      48 genes. Most of these genes are in the mitogen-activated protein kinase (MAPK)
      family. Taken together, our results provide a platform for further studies to
      identify the biological functions of CaNAC genes.

PMID- 29596351
TI  - The DaNa2.0 Knowledge Base Nanomaterials-An Important Measure Accompanying
      Nanomaterials Development.
AB  - Nanotechnology is closely related to the tailored manufacturing of nanomaterials
      for a huge variety of applications. However, such applications with newly
      developed materials are also a reason for concern. The DaNa2.0 project provides
      information and support for these issues on the web in condensed and easy-to
      understand wording. Thus, a key challenge in the field of advanced materials
      safety research is access to correct and reliable studies and validated results.
      For nanomaterials, there is currently a continuously increasing amount of
      publications on toxicological issues, but criteria to evaluate the quality of
      these studies are necessary to use them e.g., for regulatory purposes. DaNa2.0
      discusses scientific results regarding 26 nanomaterials based on actual
      literature that has been selected after careful evaluation following a literature
      criteria checklist. This checklist is publicly available, along with a selection
      of standardized operating protocols (SOPs) established by different projects. The
      spectrum of information is rounded off by further articles concerning basics or
      crosscutting topics in nanosafety research. This article is intended to give an
      overview on DaNa2.0 activities to support reliable toxicity testing and science
      communication alike.

PMID- 29596350
TI  - Recurrent Renal Colic in a Patient with Munchausen Syndrome.
AB  - BACKGROUND: In most of the cases regarding children, factitious disorders (FDs)
      are intentionally produced by parents. Less attention is paid to FDs in which a
      child or adolescent intentionally induces or falsifies the disease to attain a
      patient's role. CASE PRESENTATION: A 13-year-old immigrated and adopted boy
      previously underwent an operation for renal joint syndrome and was affected by
      recurrent episodes of renal colic. The boy was admitted reporting acute left
      flank pain with scars on the mucous face of his prepuce and had a recent previous
      hospitalization for the same reason. Laboratory tests and radiological findings
      did not reveal any morphological or functional alterations. Self-induced FD was
      suspected, and a psychiatric consultation was performed. After psychiatric
      consultation and remission of the symptoms with a placebo, a diagnosis of
      Munchausen syndrome was suspected. The patient's uncle was not initially
      convinced of the diagnosis. Some videos clearly showed that the boy was handling
      his prepuce to excrete stones, explaining the scars. A therapeutic plan with
      psychiatrist support was later accepted with a positive outcome. No further signs
      and symptoms of renal colic were reported. CONCLUSIONS: It is recommended that
      paediatricians include FD in the differential diagnosis of a persistent and
      unexplained medical condition. If suspicion arises, confirmation and long-term
      therapy by a group of qualified specialists, including psychiatrists, should be
      planned.

PMID- 29596353
TI  - Benveniste's Experiments Explained by a Non-Conventional Experimenter Effect.
AB  - Background: Benveniste's biology experiments suggested the existence of molecular
      like effects without molecules ("memory of water"). In this article, it is
      proposed that these disputed experiments could have been the consequence of a
      previously unnoticed and non-conventional experimenter effect. Methods: A
      probabilistic modelling is built in order to describe an elementary laboratory
      experiment. A biological system is modelled with two possible states ("resting"
      and "activated") and exposed to two experimental conditions labelled "control"
      and "test", but both are biologically inactive. The modelling takes into account
      not only the biological system, but also the experimenters. In addition, an
      outsider standpoint is adopted to describe the experimental situation. Results: A
      classical approach suggests that, after experiment completion, the "control" and
      "test" labels of biologically-inactive conditions should both be associated with
      the "resting" state (i.e., no significant relationship between labels and system
      states). However, if the fluctuations of the biological system are also
      considered, a quantum-like relationship emerges and connects labels and system
      states (analogous to a biological "effect" without molecules). Conclusions: No
      hypotheses about water properties or other exotic explanations are needed to
      describe Benveniste's experiments, including their unusual features. This
      modelling could be extended to other experimental situations in biology,
      medicine, and psychology.

PMID- 29596352
TI  - Electrospun Composites of Polycaprolactone and Porous Silicon Nanoparticles for
      the Tunable Delivery of Small Therapeutic Molecules.
AB  - This report describes the use of an electrospun composite of poly(epsilon
      caprolactone) (PCL) fibers and porous silicon (pSi) nanoparticles (NPs) as an
      effective system for the tunable delivery of camptothecin (CPT), a small
      therapeutic molecule. Both materials are biodegradable, abundant, low-cost, and
      most importantly, have no known cytotoxic effects. The composites were treated
      with and without sodium hydroxide (NaOH) to investigate the wettability of the
      porous network for drug release and cell viability measurements. CPT release and
      subsequent cell viability was also investigated. We observed that the cell death
      rate was not only affected by the addition of our CPT carrier, pSi, but also by
      increasing the rate of dissolution via treatment with NaOH. This is the first
      example of loading pSi NPs as a therapeutics nanocarrier into electronspun PCL
      fibers and this system opens up new possibilities for the delivery of molecular
      therapeutics.

PMID- 29596354
TI  - A New Breviane Spiroditerpenoid from the Marine-Derived Fungus Penicillium sp.
      TJ403-1.
AB  - Marine-derived fungi are a promising and untapped reservoir for discovering
      structurally interesting and pharmacologically active natural products. In our
      efforts to identify novel bioactive compounds from marine-derived fungi, four
      breviane spiroditerpenoids, including a new compound, brevione O (1), and three
      known compounds breviones I (2), J (3), and H (4), together with a known
      diketopiperazine alkaloid brevicompanine G (5), were isolated and identified from
      an ethyl acetate extract of the fermented rice substrate of the coral-derived
      fungus Penicillium sp. TJ403-1. The absolute structure of 1 was elucidated by
      HRESIMS, one- and two-dimensional NMR spectroscopic data, and a comparison of its
      electronic circular dichroism (ECD) spectrum with the literature. Moreover, we
      confirmed the absolute configuration of 5 by single-crystal X-ray
      crystallography. All the isolated compounds were evaluated for isocitrate
      dehydrogenase 1 (IDH1) inhibitory activity and cytotoxicity, and compound 2
      showed significant inhibitory activities against HL-60, A-549, and HEP3B tumor
      cell lines with IC50 values of 4.92 +/- 0.65, 8.60 +/- 1.36, and 5.50 +/- 0.67
      uM, respectively.

PMID- 29596355
TI  - Occurrence of Functional Molecules in the Flowers of Tea (Camellia sinensis)
      Plants: Evidence for a Second Resource.
AB  - Tea (Camellia sinensis) is an important crop, and its leaves are used to make the
      most widely consumed beverage, aside from water. People have been using leaves
      from tea plants to make teas for a long time. However, less attention has been
      paid to the flowers of tea plants, which is a waste of an abundant resource. In
      the past 15 years, researchers have attempted to discover, identify, and evaluate
      functional molecules from tea flowers, and have made insightful and useful
      discoveries. Here, we summarize the recent investigations into these functional
      molecules in tea flowers, including functional molecules similar to those in tea
      leaves, as well as the preponderant functional molecules in tea flowers. Tea
      flowers contain representative metabolites similar to those of tea leaves, such
      as catechins, flavonols, caffeine, and amino acids. The preponderant functional
      molecules in tea flowers include saponins, polysaccharides, aromatic compounds,
      spermidine derivatives, and functional proteins. We also review the safety and
      biological functions of tea flowers. Tea flower extracts are proposed to be of no
      toxicological concern based on evidence from the evaluation of mutagenicity, and
      acute and subchronic toxicity in rats. The presence of many functional
      metabolites in tea flowers indicates that tea flowers possess diverse biological
      functions, which are mostly related to catechins, polysaccharides, and saponins.
      Finally, we discuss the potential for, and challenges facing, future applications
      of tea flowers as a second resource from tea plants.

PMID- 29596356
TI  - Dissipation and Migration of Pyrethroids in Auricularia polytricha Mont. from
      Cultivation to Postharvest Processing and Dietary Risk.
AB  - In order to ensure raw consumption safety the dissipation behavior, migration,
      postharvest processing, and dietary risk assessment of five pyrethroids in
      mushroom (Auricularia polytricha Mont.) cultivated under Chinese greenhouse-field
      conditions. Half-lives (t1/2) of pyrethroids in fruiting body and substrate
      samples were 3.10-5.26 and 17.46-40.06 d, respectively. Fenpropathrin dissipated
      rapidly in fruiting bodies (t1/2 3.10 d); bifenthrin had the longest t1/2. At
      harvest, pyrethroid residues in A. polytricha (except fenpropathrin) were above
      the respective maximum residue limits (MRLs). Some migration of lambda
      cyhalothrin was observed in the substrate-fruit body system. In postharvest
      processing, sun-drying and soaking reduced pyrethroid residues by 25-83%. We
      therefore recommend that consumers soak these mushrooms in 0.5% NaHCO3 at 50 
      degrees C for 90 min. Pyrethroids exhibit a particularly low PF value of 0.08
      0.13%, resulting in a negligible exposure risk upon mushroom consumption. This
      study provides guidance for the safe application of pyrethroids to edible fungi,
      and for the establishment of MRLs in mushrooms to reduce pesticide exposure in
      humans.

PMID- 29596357
TI  - The Influence of Metakaolinite on the Development of Thermal Cracks in a Cement
      Matrix.
AB  - In the paper the cluster cracks of cement paste that has been modified with
      metakaolinite was analyzed. The samples were loaded with an elevated temperature
      based on a thermal shock. To describe the crack structure, three stereological
      parameters were proposed to measure: (i) the cluster average area ( A - ); (ii)
      the cluster average perimeter ( L - ); and (iii) the crack average width ( I - ).
      The computer image analysis was implemented in the study, and 4 series of samples
      were subjected to the examination. In two series, metakaolinite was used as a
      substitute for 10% of a cement's mass. An assessment of the basic physico
      mechanical characteristics of the cement matrix was also carried out. The
      structure of the cement paste was considered as a highly concentrated dispersion
      system, in which the interactions between the cement's grains at the initial
      stage of the structure self-assembly affect the crack characteristics. The study
      has been supplemented with microstructural investigations using a scanning
      electron microscope and an X-ray microanalyzer. The conducted research indicated
      the direction of changes in the geometrical characteristics of thermal cracks if
      the technological variables of the material are subjected to modification. It was
      also confirmed that the cluster structures have fractal character and can be
      analyzed and observed on many levels of a structural heterogeneity.

PMID- 29596358
TI  - Porous Polyethylene Coated with Functionalized Hydroxyapatite Particles as a Bone
      Reconstruction Material.
AB  - In this study, porous polyethylene scaffolds were examined as bone substitutes in
      vitro and in vivo in critical-sized calvarial bone defects in transgenic Sprague
      Dawley rats. A microscopic examination revealed that the pores appeared to be
      interconnected across the material, making them suitable for cell growth. The
      creep recovery behavior of porous polyethylene at different loads indicated that
      the creep strain had two main portions. In both portions, strain increased with
      increased applied load and temperature. In terms of the thermographic behavior of
      the material, remarkable changes in melting temperature and heat fusion were
      revealed with increased the heating rates. The tensile strength results showed
      that the material was sensitive to the strain rate and that there was adequate
      mechanical strength to support cell growth. The in vitro cell culture results
      showed that human bone marrow mesenchymal stem cells attached to the porous
      polyethylene scaffold. Calcium sulfate-hydroxyapatite (CS-HA) coating of the
      scaffold not only improved attachment but also increased the proliferation of
      human bone marrow mesenchymal stem cells. In vivo, histological analysis showed
      that the study groups had active bone remodeling at the border of the defect.
      Bone regeneration at the border was also evident, which confirmed that the
      polyethylene acted as an osteoconductive bone graft. Furthermore, bone formation
      inside the pores of the coated polyethylene was also noted, which would enhance
      the process of osteointegration.

PMID- 29596359
TI  - Advances in Materials for Recent Low-Profile Implantable Bioelectronics.
AB  - The rapid development of micro/nanofabrication technologies to engineer a variety
      of materials has enabled new types of bioelectronics for health monitoring and
      disease diagnostics. In this review, we summarize widely used electronic
      materials in recent low-profile implantable systems, including traditional metals
      and semiconductors, soft polymers, biodegradable metals, and organic materials.
      Silicon-based compounds have represented the traditional materials in medical
      devices, due to the fully established fabrication processes. Examples include
      miniaturized sensors for monitoring intraocular pressure and blood pressure,
      which are designed in an ultra-thin diaphragm to react with the applied pressure.
      These sensors are integrated into rigid circuits and multiple modules; this
      brings challenges regarding the fundamental material's property mismatch with the
      targeted human tissues, which are intrinsically soft. Therefore, many polymeric
      materials have been investigated for hybrid integration with well-characterized
      functional materials such as silicon membranes and metal interconnects, which
      enable soft implantable bioelectronics. The most recent trend in implantable
      systems uses transient materials that naturally dissolve in body fluid after a
      programmed lifetime. Such biodegradable metallic materials are advantageous in
      the design of electronics due to their proven electrical properties.
      Collectively, this review delivers the development history of materials in
      implantable devices, while introducing new bioelectronics based on bioresorbable
      materials with multiple functionalities.

PMID- 29596360
TI  - A Reversible Bis(Salamo)-Based Fluorescence Sensor for Selective Detection of
      Cd2+ in Water-Containing Systems and Food Samples.
AB  - A novel, simple, highly selective, and sensitive fluorescence chemosensor for
      detecting Cd2+ that was constructed from a bis(salamo)-type compound (H4L) with
      two N2O2 chelating moieties as ionophore was successfully developed. Sensor H4L
      could show fluorescence turn-on response rapidly and significant selectivity to
      Cd2+ over many other metallic ions (Cu2+, Ba2+, Ca2+, K+, Cr3+, Mn2+, Sr2+, Co2+,
      Na+, Li+, Ni2+, Ag+, and Zn2+), and a clear change in color from colorless to
      yellow that can be very easily observed via the naked eyes in the existence of
      Cd2+, while other metallic ions do not induce such a change. Interestingly, its
      fluorescent intensity was increased sharply with the increased concentration of
      Cd2+. The detection limit of sensor H4L towards Cd2+ was down to 8.61 * 10-7 M.

PMID- 29596361
TI  - Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy
      (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of
      Intravenous Iron Therapy for OIT-Nonresponders.
AB  - Background: We determined optimal serum ferritin for oral iron therapy (OIT) in
      hemodialysis (HD) patients with iron deficiency anemia (IDA)/minor inflammation,
      and benefit of intravenous iron therapy (IIT) for OIT-nonresponders. Methods:
      Inclusion criteria were IDA (Hb <120 g/L, serum ferritin <227.4 pmol/L).
      Exclusion criteria were inflammation (C-reactive protein (CRP) >= 5 mg/L),
      bleeding, or cancer. IIT was withheld >3 months before the study. DeltaHb >= 20
      g/L above baseline or maintaining target Hb (tHB; 120-130 g/L) was considered
      responsive. Fifty-one patients received OIT (ferrous fumarate, 50 mg/day) for 3
      months; this continued in OIT-responders but was switched to IIT (saccharated
      ferric oxide, 40 mg/week) in OIT-nonresponders for 4 months. All received
      continuous erythropoietin receptor activator (CERA). Hb, ferritin, hepcidin-25,
      and CERA dose were measured. Results: Demographics before OIT were similar
      between OIT-responders and OIT-nonresponders except low Hb and high triglycerides
      in OIT-nonresponders. Thirty-nine were OIT-responders with reduced CERA dose. Hb
      rose with a peak at 5 months. Ferritin and hepcidin-25 continuously increased. Hb
      positively correlated with ferritin in OIT-responders (r = 0.913, p = 0.03) till
      5 months after OIT. The correlation equation estimated optimal ferritin of 30-40
      ng/mL using tHb (120-130 g/L). Seven OIT-nonresponders were IIT-responders.
      Conclusions: Optimal serum ferritin for OIT is 67.4-89.9 pmol/L in HD patients
      with IDA/minor inflammation. IIT may be a second line of treatment for OIT
      nonreponders.

PMID- 29596362
TI  - Both Mother and Infant Require a Vitamin D Supplement to Ensure That Infants'
      Vitamin D Status Meets Current Guidelines.
AB  - We examined the association between maternal vitamin D intake during
      breastfeeding with their infants' vitamin D status in infants who did or did not
      receive vitamin D supplements to determine whether infant supplementation was
      sufficient. Using plasma from a subset of breastfed infants in the APrON (Alberta
      Pregnant Outcomes and Nutrition) cohort, vitamin D status was measured by liquid
      chromatography-tandem mass spectrometry. Maternal and infants' dietary data were
      obtained from APrON's dietary questionnaires. The median maternal vitamin D
      intake was 665 International Units (IU)/day, while 25% reported intakes below the
      recommended 400 IU/day. Of the 224 infants in the cohort, 72% were exclusively
      breastfed, and 90% were receiving vitamin D supplements. Infants' median 25(OH)D
      was 96.0 nmol/L (interquartile ranges (IQR) 77.6-116.2), and 25% had 25(OH)D < 75
      nmol/L. An adjusted linear regression model showed that, with a 100 IU increase
      in maternal vitamin D intake, infants' 25(OH)D increased by 0.9 nmol/L
      controlling for race, season, mid-pregnancy maternal 25(OH)D, birthweight, and
      whether the infant received daily vitamin D supplement (beta = 0.008, 95%
      confidence interval (CI) 0.002, 0.13). These results suggest that, to ensure
      infant optimal vitamin D status, not only do infants require a supplement, but
      women also need to meet current recommended vitamin D intake during
      breastfeeding.

PMID- 29596363
TI  - PCLPred: A Bioinformatics Method for Predicting Protein-Protein Interactions by
      Combining Relevance Vector Machine Model with Low-Rank Matrix Approximation.
AB  - Protein-protein interactions (PPI) are key to protein functions and regulations
      within the cell cycle, DNA replication, and cellular signaling. Therefore,
      detecting whether a pair of proteins interact is of great importance for the
      study of molecular biology. As researchers have become aware of the importance of
      computational methods in predicting PPIs, many techniques have been developed for
      performing this task computationally. However, there are few technologies that
      really meet the needs of their users. In this paper, we develop a novel and
      efficient sequence-based method for predicting PPIs. The evolutionary features
      are extracted from the position-specific scoring matrix (PSSM) of protein. The
      features are then fed into a robust relevance vector machine (RVM) classifier to
      distinguish between the interacting and non-interacting protein pairs. In order
      to verify the performance of our method, five-fold cross-validation tests are
      performed on the Saccharomyces cerevisiae dataset. A high accuracy of 94.56%,
      with 94.79% sensitivity at 94.36% precision, was obtained. The experimental
      results illustrated that the proposed approach can extract the most significant
      features from each protein sequence and can be a bright and meaningful tool for
      the research of proteomics.

PMID- 29596365
TI  - UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1.
AB  - FOXM1 (forkhead box protein M1) is a transcription factor that participates in
      all stages of tumor development, mainly through the control of cell cycle and
      proliferation, regulating the expression of genes involved in G1/S and G2/M
      transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C)
      is a member of the anaphase promoting complex/cyclosome, promoting the
      degradation of several target proteins along cell cycle progression, during
      metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a
      wide range of different solid tumors. Therefore, the aim of this study was to
      investigate whether UBE2C is a transcriptional target of FOXM1, using esophageal
      squamous cell carcinoma (ESCC) as a model, in addition to several cancer
      deposited data. Our results show that FOXM1 and UBE2C expression present a
      positive correlation in normal tissues and in 25 distinct tumor types, including
      ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to UBE2C
      promoter region in ESCC cell line and transcriptionally activates it, leading to
      UBE2C upregulation. In conclusion, this study provides evidences that FOXM1
      transcriptionally regulates UBE2C expression in ESCC and their deregulation may
      be a general phenomenon in human neoplasias.

PMID- 29596364
TI  - Non-Coding RNAs and Endometrial Cancer.
AB  - Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and
      neoplastic transformation. Recent studies have tried to clarify the significance
      of these information carriers in the genesis and progression of various cancers
      and their use as biomarkers for the disease; possible targets for the inhibition
      of growth and invasion by the neoplastic cells have been suggested. The
      significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and
      melanoma has been amply investigated with important results. Recently, the role
      of long non-coding RNAs (lncRNAs) has also been included in cancer studies.
      Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small
      ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs),
      antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs
      (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs),
      lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent
      literature produced in the last three years was extracted from PubMed by two
      independent readers, which was then selected for the possible relation between
      ncRNAs, oncogenesis in general, and EC in particular.

PMID- 29596366
TI  - Temporal and Spatial Variation in, and Population Exposure to, Summertime Ground
      Level Ozone in Beijing.
AB  - Ground-level ozone pollution in Beijing has been causing concern among the public
      due to the risks posed to human health. This study analyzed the temporal and
      spatial distribution of, and investigated population exposure to, ground-level
      ozone. We analyzed hourly ground-level ozone data from 35 ambient air quality
      monitoring sites, including urban, suburban, background, and traffic monitoring
      sites, during the summer in Beijing from 2014 to 2017. The results showed that
      the four-year mean ozone concentrations for urban, suburban, background, and
      traffic monitoring sites were 95.1, 99.8, 95.9, and 74.2 MUg/m3, respectively. A
      total of 44, 43, 45, and 43 days exceeded the Chinese National Ambient Air
      Quality Standards (NAAQS) threshold for ground-level ozone in 2014, 2015, 2016,
      and 2017, respectively. The mean ozone concentration was higher in suburban sites
      than in urban sites, and the traffic monitoring sites had the lowest
      concentration. The diurnal variation in ground-level ozone concentration at the
      four types of monitoring sites displayed a single-peak curve. The peak and valley
      values occurred at 3:00-4:00 p.m. and 7:00 a.m., respectively. Spatially, ground
      level ozone concentrations decreased in gradient from the north to the south.
      Population exposure levels were calculated based on ground-level ozone
      concentrations and population data. Approximately 50.38%, 44.85%, and 48.49% of
      the total population of Beijing were exposed to ground-level ozone concentrations
      exceeding the Chinese NAAQS threshold in 2014, 2015, and 2016, respectively.

PMID- 29596367
TI  - Carbene Transfer Reactions Catalysed by Dyes of the Metalloporphyrin Group.
AB  - Carbene transfer reactions are very important transformations in organic
      synthesis, allowing the generation of structurally challenging products by
      catalysed cyclopropanation, cyclopropenation, carbene C-H, N-H, O-H, S-H, and Si
      H insertion, and olefination of carbonyl compounds. In particular, chiral and
      achiral metalloporphyrins have been successfully explored as biomimetic catalysts
      for these carbene transfer reactions under both homogeneous and heterogeneous
      conditions. In this work the use of synthetic metalloporphyrins (MPorph, M = Fe,
      Ru, Os, Co, Rh, Ir, Sn) as homogeneous or heterogeneous catalysts for carbene
      transfer reactions in the last years is reviewed, almost exclusively focused on
      the literature since the year 2010, except when reference to older publications
      was deemed to be crucial.

PMID- 29596368
TI  - UHPLC-MS Metabolome Fingerprinting: The Isolation of Main Compounds and
      Antioxidant Activity of the Andean Species Tetraglochin ameghinoi (Speg.) Speg.
AB  - The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and
      methanol extracts (MeOH-E) from the aerial parts of the native South American
      plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their
      antioxidant and antibacterial activities. The antioxidant properties were
      evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing
      antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the
      antibacterial activity was performed against Gram-positive and Gram-negative
      bacteria according to the Clinical and Laboratory Standards Institute (CLSI)
      guidelines. The chemical and biological analyses of this plant are very important
      since this bush is currently used in traditional medicine as a cholagogue and
      digestive. The polar MeOH-E showed the highest antioxidant activities (17.70
      ug/mL in the DPPH assay, 381.43 +/- 22.38 mM TE/g extract in the FRAP assay,
      387.76 +/- 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP
      assay) and it was selected for chromatographic isolation of its components. These
      components were found to be four acetophenones, including the new
      phloracetophenone glucoside: 4',6',-dihydroxy-2'-O-(6"-acetyl)-beta-d
      glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)
      3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was
      elucidated by NMR and MS methods. In addition, twenty-six compounds, including
      five of these acetophenone derivatives, two sugars, six flavonoids, eleven
      phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA
      analysis on the MeOH-E. The results support the medicinal use of the plant.

PMID- 29596369
TI  - New Statistical Approach to Apportion Dietary Sources of Iodine Intake: Findings
      from Kenya, Senegal and India.
AB  - Progress of national Universal Salt Iodization (USI) strategies is typically
      assessed by household coverage of adequately iodized salt and median urinary
      iodine concentration (UIC) in spot urine collections. However, household coverage
      does not inform on the iodized salt used in preparation of processed foods
      outside homes, nor does the total UIC reflect the portion of population iodine
      intake attributable to the USI strategy. This study used data from three
      population-representative surveys of women of reproductive age (WRA) in Kenya,
      Senegal and India to develop and illustrate a new approach to apportion the
      population UIC levels by the principal dietary sources of iodine intake, namely
      native iodine, iodine in processed food salt and iodine in household salt. The
      technique requires measurement of urinary sodium concentrations (UNaC) in the
      same spot urine samples collected for iodine status assessment. Taking into
      account the different complex survey designs of each survey, generalized linear
      regression (GLR) analyses were performed in which the UIC data of WRA was set as
      the outcome variable that depends on their UNaC and household salt iodine (SI)
      data as explanatory variables. Estimates of the UIC portions that correspond to
      iodine intake sources were calculated with use of the intercept and regression
      coefficients for the UNaC and SI variables in each country's regression equation.
      GLR coefficients for UNaC and SI were significant in all country-specific models.
      Rural location did not show a significant association in any country when
      controlled for other explanatory variables. The estimated UIC portion from native
      dietary iodine intake in each country fell below the minimum threshold for iodine
      sufficiency. The UIC portion arising from processed food salt in Kenya was
      substantially higher than in Senegal and India, while the UIC portions from
      household salt use varied in accordance with the mean level of household SI
      content in the country surveys. The UIC portions and all-salt-derived iodine
      intakes found in this study were illustrative of existing differences in national
      USI legislative frameworks and national salt supply situations between countries.
      The approach of apportioning the population UIC from spot urine collections may
      be useful for future monitoring of change in iodine nutrition from reduced salt
      use in processed foods and in households.

PMID- 29596371
TI  - Experimental Characterization of Stress- and Strain-Dependent Stiffness in
      Grouted Rock Masses.
AB  - Grouting of fractured rock mass prior to excavation results in grout-filled
      discontinuities that govern the deformation characteristics of a site. The
      influence of joint characteristics on the properties of grouted rocks is
      important in assessing the effects of grouting on jointed rock mass. However,
      grouting remains a predominantly empirical practice and the effects of grouting
      on rock joint behavior and material properties have yet to be accurately
      assessed. Granular materials, including jointed rocks, typically display
      nonlinear strain-dependent responses that can be characterized by the shear
      modulus degradation curve. In this study, the effects of grouting on the strain
      dependent shear stiffness of jointed rock mass were investigated at the small
      strain (below 10-5) and mid-strain (10-5 to 10-3) ranges using the quasi-static
      resonant column test and rock mass dynamic test devices. The effects of curing
      time, axial stress, initial joint roughness, and grouted joint thickness were
      examined. The results show that (1) grouting of rock joints leads to decreased
      stress sensitivity and increased small-strain shear stiffness for all tested
      samples; (2) the grouted rock samples display similar modulus degradation
      characteristics as the applied grout material; (3) the initial joint roughness
      determines the stress-dependent behaviors and general stiffness range of the
      jointed and grouted rocks, but the strain-dependent behaviors are dependent on
      the properties of the grout material; (4) increased grouted joint thickness
      results in larger contribution of the grout properties in the overall grouted
      rock mass.

PMID- 29596370
TI  - Production, Characterization and Biocompatibility Evaluation of Collagen
      Membranes Derived from Marine Sponge Chondrosia reniformis Nardo, 1847.
AB  - Collagen is involved in the formation of complex fibrillar networks, providing
      the structural integrity of tissues. Its low immunogenicity and mechanical
      properties make this molecule a biomaterial that is extremely suitable for tissue
      engineering and regenerative medicine (TERM) strategies in human health issues.
      Here, for the first time, we performed a thorough screening of four different
      methods to obtain sponge collagenous fibrillar suspensions (FSs) from C.
      reniformis demosponge, which were then chemically, physically, and biologically
      characterized, in terms of protein, collagen, and glycosaminoglycans content,
      viscous properties, biocompatibility, and antioxidant activity. These four FSs
      were then tested for their capability to generate crosslinked or not thin sponge
      collagenous membranes (SCMs) that are suitable for TERM purposes. Two types of
      FSs, of the four tested, were able to generate SCMs, either from crosslinking or
      not, and showed good mechanical properties, enzymatic degradation resistance,
      water binding capacity, antioxidant activity, and biocompatibility on both
      fibroblast and keratinocyte cell cultures. Finally, our results demonstrate that
      it is possible to adapt the extraction procedure in order to alternatively
      improve the mechanical properties or the antioxidant performances of the derived
      biomaterial, depending on the application requirements, thanks to the versatility
      of C. reniformis extracellular matrix extracts.

PMID- 29596372
TI  - Fabrication and Characterization of Aligned Flexible Lead-Free Piezoelectric
      Nanofibers for Wearable Device Applications.
AB  - Flexible lead-free piezoelectric nanofibers, based on BNT-ST (0.78Bi0.5Na0.5TiO3
      0.22SrTiO3) ceramic and poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE)
      copolymers, were fabricated by an electrospinning method and the effects of the
      degree of alignment in the nanofibers on the piezoelectric characteristics were
      investigated. The microstructure of the lead-free piezoelectric nanofibers was
      observed by field emission scanning electron microscope (FE-SEM) and the
      orientation was analyzed by fast Fourier transform (FFT) images. X-ray
      diffraction (XRD) analysis confirmed that the phase was not changed by the
      electrospinning process and maintained a perovskite phase. Polarization-electric
      field (P-E) loops and piezoresponse force microscopy (PFM) were used to
      investigate the piezoelectric properties of the piezoelectric nanofibers,
      according to the degree of alignment-the well aligned piezoelectric nanofibers
      had higher piezoelectric properties. Furthermore, the output voltage of the
      aligned lead-free piezoelectric nanofibers was measured according to the
      vibration frequency and the bending motion and the aligned piezoelectric
      nanofibers with a collector rotation speed of 1500 rpm performed the best.

PMID- 29596373
TI  - Few-Layer MoS2 Nanodomains Decorating TiO2 Nanoparticles: A Case Study for the
      Photodegradation of Carbamazepine.
AB  - S-doped TiO2 and hybrid MoS2/TiO2 systems have been synthesized, via the
      sulfidation with H2S of the bare TiO2 and of MoOx supported on TiO2 systems, with
      the aim of enhancing the photocatalytic properties of TiO2 for the degradation of
      carbamazepine, an anticonvulsant drug, whose residues and metabolites are usually
      inefficiently removed in wastewater treatment plants. The focus of this study is
      to find a relationship between the morphology/structure/surface properties and
      photoactivity. The full characterization of samples reveals the strong effects of
      the H2S action on the properties of TiO2, with the formation of defects at the
      surface, as shown by transmission electron microscopy (TEM) and infrared
      spectroscopy (IR), while also the optical properties are strongly affected by the
      sulfidation treatment, with changes in the electronic states of TiO2. Meanwhile,
      the formation of small and thin few-layer MoS2 domains, decorating the TiO2
      surface, is evidenced by both high-resolution transmission electron microscopy
      (HRTEM) and UV-Vis/Raman spectroscopies, while Fourier-transform infrared (FTIR)
      spectra give insights into the nature of Ti and Mo surface sites. The most
      interesting findings of our research are the enhanced photoactivity of the
      MoS2/TiO2 hybrid photocatalyst toward the carbamazepine mineralization.
      Surprisingly, the formation of hazardous compounds (i.e., acridine derivatives),
      usually obtained from carbamazepine, is precluded when treated with MoS2/TiO2
      systems.

PMID- 29596374
TI  - Dissecting the Mutational Landscape of Cutaneous Melanoma: An Omic Analysis Based
      on Patients from Greece.
AB  - Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin
      fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays
      after diagnostic examination, but isolated nucleic acids often suffer from
      degradation. Here, for the first time, we examine primary melanomas from Greek
      patients, using whole exome sequencing, so as to derive their mutational profile.
      Application of a bioinformatic framework revealed a total of 10,030 somatic
      mutations. Regarding the genes containing putative protein-altering mutations, 73
      were common in at least three patients. Sixty-five of these 73 top common genes
      have been previously identified in melanoma cases. Biological processes related
      to melanoma were affected by varied genes in each patient, suggesting differences
      in the components of a pathway possibly contributing to pathogenesis. We
      performed a multi-level analysis highlighting a short list of candidate genes
      with a probable causative role in melanoma.

PMID- 29596375
TI  - Comparative Performance Analysis of Support Vector Machine, Random Forest,
      Logistic Regression and k-Nearest Neighbours in Rainbow Trout (Oncorhynchus
      Mykiss) Classification Using Image-Based Features.
AB  - The main aim of this study was to develop a new objective method for evaluating
      the impacts of different diets on the live fish skin using image-based features.
      In total, one-hundred and sixty rainbow trout (Oncorhynchus mykiss) were fed
      either a fish-meal based diet (80 fish) or a 100% plant-based diet (80 fish) and
      photographed using consumer-grade digital camera. Twenty-three colour features
      and four texture features were extracted. Four different classification methods
      were used to evaluate fish diets including Random forest (RF), Support vector
      machine (SVM), Logistic regression (LR) and k-Nearest neighbours (k-NN). The SVM
      with radial based kernel provided the best classifier with correct classification
      rate (CCR) of 82% and Kappa coefficient of 0.65. Although the both LR and RF
      methods were less accurate than SVM, they achieved good classification with CCR
      75% and 70% respectively. The k-NN was the least accurate (40%) classification
      model. Overall, it can be concluded that consumer-grade digital cameras could be
      employed as the fast, accurate and non-invasive sensor for classifying rainbow
      trout based on their diets. Furthermore, these was a close association between
      image-based features and fish diet received during cultivation. These procedures
      can be used as non-invasive, accurate and precise approaches for monitoring fish
      status during the cultivation by evaluating diet's effects on fish skin.

PMID- 29596376
TI  - Quantifying the Accuracy of Digital Hemispherical Photography for Leaf Area Index
      Estimates on Broad-Leaved Tree Species.
AB  - Digital hemispherical photography (DHP) has been widely used to estimate leaf
      area index (LAI) in forestry. Despite the advancement in the processing of
      hemispherical images with dedicated tools, several steps are still manual and
      thus easily affected by user's experience and sensibility. The purpose of this
      study was to quantify the impact of user's subjectivity on DHP LAI estimates for
      broad-leaved woody canopies using the software Can-Eye. Following the ISO 5725
      protocol, we quantified the repeatability and reproducibility of the method, thus
      defining its precision for a wide range of broad-leaved canopies markedly
      differing for their structure. To get a complete evaluation of the method
      accuracy, we also quantified its trueness using artificial canopy images with
      known canopy cover. Moreover, the effect of the segmentation method was analysed.
      The best results for precision (restrained limits of repeatability and
      reproducibility) were obtained for high LAI values (>5) with limits corresponding
      to a variation of 22% in the estimated LAI values. Poorer results were obtained
      for medium and low LAI values, with a variation of the estimated LAI values that
      exceeded the 40%. Regardless of the LAI range explored, satisfactory results were
      achieved for trees in row-structured plantations (limits almost equal to the 30%
      of the estimated LAI). Satisfactory results were achieved for trueness,
      regardless of the canopy structure. The paired t-test revealed that the effect of
      the segmentation method on LAI estimates was significant. Despite a non
      negligible user effect, the accuracy metrics for DHP are consistent with those
      determined for other indirect methods for LAI estimates, confirming the overall
      reliability of DHP in broad-leaved woody canopies.

PMID- 29596377
TI  - A Novel Model to Simulate Flexural Complements in Compliant Sensor Systems.
AB  - The main challenge in analyzing compliant sensor systems is how to calculate the
      large deformation of flexural complements. Our study proposes a new model that is
      called the spline pseudo-rigid-body model (spline PRBM). It combines dynamic
      spline and the pseudo-rigid-body model (PRBM) to simulate the flexural
      complements. The axial deformations of flexural complements are modeled by using
      dynamic spline. This makes it possible to consider the nonlinear compliance of
      the system using four control points. Three rigid rods connected by two revolute
      (R) pins with two torsion springs replace the three lines connecting the four
      control points. The kinematic behavior of the system is described using Lagrange
      equations. Both the optimization and the numerical fitting methods are used for
      resolving the characteristic parameters of the new model. An example is given of
      a compliant mechanism to modify the accuracy of the model. The spline PRBM is
      important in expanding the applications of the PRBM to the design and simulation
      of flexural force sensors.

PMID- 29596378
TI  - Range Sensor-Based Efficient Obstacle Avoidance through Selective Decision
      Making.
AB  - In this paper, we address a collision avoidance method for mobile robots. Many
      conventional obstacle avoidance methods have been focused solely on avoiding
      obstacles. However, this can cause instability when passing through a narrow
      passage, and can also generate zig-zag motions. We define two strategies for
      obstacle avoidance, known as Entry mode and Bypass mode. Entry mode is a pattern
      for passing through the gap between obstacles, while Bypass mode is a pattern for
      making a detour around obstacles safely. With these two modes, we propose an
      efficient obstacle avoidance method based on the Expanded Guide Circle (EGC)
      method with selective decision-making. The simulation and experiment results show
      the validity of the proposed method.

PMID- 29596379
TI  - Natural Resistance Associated Macrophage Protein Is Involved in Immune Response
      of Blunt Snout Bream, Megalobrama amblycephala.
AB  - The natural resistance-associated macrophage protein gene (Nramp), has been
      identified as one of the significant candidate genes responsible for modulating
      vertebrate natural resistance to intracellular pathogens. Here, we identified and
      characterized a new Nramp family member, named as maNramp, in the blunt snout
      bream. The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open
      reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR. The
      deduced protein (maNRAMP) possesses the typical structural features of NRAMP
      protein family, including 12 transmembrane domains, three N-linked glycosylation
      sites, and a conserved transport motif. Phylogenetic analysis revealed that
      maNRAMP shares the significant sequence consistency with other teleosts, and
      shows the higher sequence similarity to mammalian Nramp2 than Nramp1. It was
      found that maNramp expressed ubiquitously in all normal tissues tested, with the
      highest abundance in the spleen, followed by the head kidney and intestine, and
      less abundance in the muscle, gill, and kidney. After lipopolysaccharide (LPS)
      stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a
      peak level at 6 h. Altogether, these results indicated that maNramp might be
      related to fish innate immunity and similar to mammalian Nramp1 in function.

PMID- 29596380
TI  - Reconsidering the Relationship between Air Pollution and Deprivation.
AB  - This paper critically examines the relationship between air pollution and
      deprivation. We argue that focusing on a particular economic or social model of
      urban development might lead one to erroneously expect all cities to converge
      towards a particular universal norm. A naive market sorting model, for example,
      would predict that poor households will eventually be sorted into high pollution
      areas, leading to a positive relationship between air pollution and deprivation.
      If, however, one considers a wider set of theoretical perspectives, the
      anticipated relationship between air pollution and deprivation becomes more
      complex and idiosyncratic. Specifically, we argue the relationship between
      pollution and deprivation can only be made sense of by considering processes of
      risk perception, path dependency, gentrification and urbanization. Rather than
      expecting all areas to eventually converge to some universal norm, we should
      expect the differences in the relationship between air pollution and deprivation
      across localities to persist. Mindful of these insights, we propose an approach
      to modeling which does not impose a geographically fixed relationship. Results
      for Scotland reveal substantial variations in the observed relationships over
      space and time, supporting our argument.

PMID- 29596381
TI  - Resveratrol Suppresses the Growth and Enhances Retinoic Acid Sensitivity of
      Anaplastic Thyroid Cancer Cells.
AB  - Anaplastic thyroid cancer (ATC) is a highly lethal undifferentiated malignancy
      without reliable therapies. Retinoic acid (RA) has been employed to promote
      redifferentiation of thyroid cancers by increasing their I131 uptake and radio
      sensitivity, but its effect(s) on ATCs has not yet been ascertained. Likewise,
      resveratrol induces cancer redifferentiation but, also in this case, its effects
      on ATCs remain unknown. These issues have been addresses in the current study
      using three human ATC cell lines (THJ-11T, THJ-16T, and THJ-21T) through multiple
      experimental approaches. The results reveal that RA exerts a small inhibitory
      effect on these cell lines. In comparison with normally cultured cells, the total
      cell number in resveratrol-treated THJ-16T and THJ-21T cultures significantly
      decreased (p < 0.05), and this effect was accompanied by reduced Cyclin D1 immuno
      labeling, increased apoptotic fractions, and distinct caspase-3 activation.
      Resveratrol failed to inhibit growth but enhanced RA sensitivity of THJ-11T
      cells, suppressed peroxisome proliferator-activated receptor-beta/delta (PPAR
      beta/delta), and upregulated cellular retinoic acid-binding protein 2 (CRABP2)
      and retinoic acid receptor beta (RAR-beta) expression. Increased thyroglobulin
      (Tg) and E-cadherin levels and appearance of membranous E-cadherin were evidenced
      in resveratrol-treated THJ-11T cells. Our results demonstrate for the first time:
      (1) the therapeutic value of resveratrol by itself or in combination with RA in
      the management of ATCs, (2) the capacity of resveratrol to overcome RA resistance
      in ATC cells by reprogramming CRABP2/RAR- and fatty acid-binding protein 5
      (FABP5)/PPAR-beta/delta-mediated RA signaling, and (3) the redifferentiating
      potential of resveratrol in ATC cells.

PMID- 29596382
TI  - Mesenchymal Cells Affect Salivary Epithelial Cell Morphology on PGS/PLGA
      Core/Shell Nanofibers.
AB  - Engineering salivary glands is of interest due to the damaging effects of
      radiation therapy and the autoimmune disease Sjogren's syndrome on salivary gland
      function. One of the current problems in tissue engineering is that in vitro
      studies often fail to predict in vivo regeneration due to failure of cells to
      interact with scaffolds and of the single cell types that are typically used for
      these studies. Although poly (lactic co glycolic acid) (PLGA) nanofiber scaffolds
      have been used for in vitro growth of epithelial cells, PLGA has low compliance
      and cells do not penetrate the scaffolds. Using a core-shell electrospinning
      technique, we incorporated poly (glycerol sebacate) (PGS) into PLGA scaffolds to
      increase the compliance and decrease hydrophobicity. PGS/PLGA scaffolds promoted
      epithelial cell penetration into the scaffold and apical localization of tight
      junction proteins, which is necessary for epithelial cell function. Additionally,
      co-culture of the salivary epithelial cells with NIH3T3 mesenchymal cells on
      PGS/PLGA scaffolds facilitated epithelial tissue reorganization and apical
      localization of tight junction proteins significantly more than in the absence of
      the mesenchyme. These data demonstrate the applicability of PGS/PLGA nanofibers
      for epithelial cell self-organization and facilitation of co-culture cell
      interactions that promote tissue self-organization in vitro.

PMID- 29596384
TI  - Towards a Novel Patch Material for Cardiac Applications: Tissue-Specific
      Extracellular Matrix Introduces Essential Key Features to Decellularized Amniotic
      Membrane.
AB  - There is a growing need for scaffold material with tissue-specific bioactivity
      for use in regenerative medicine, tissue engineering, and for surgical repair of
      structural defects. We developed a novel composite biomaterial by processing
      human cardiac extracellular matrix (ECM) into a hydrogel and combining it with
      cell-free amniotic membrane via a dry-coating procedure. Cardiac biocompatibility
      and immunogenicity were tested in vitro using human cardiac fibroblasts,
      epicardial progenitor cells, murine HL-1 cells, and human immune cells derived
      from buffy coat. Processing of the ECM preserved important matrix proteins as
      demonstrated by mass spectrometry. ECM coating did not alter the mechanical
      characteristics of decellularized amniotic membrane but did cause a clear
      increase in adhesion capacity, cell proliferation and viability. Activated
      monocytes secreted less pro-inflammatory cytokines, and both macrophage
      polarization towards the pro-inflammatory M1 type and T cell proliferation were
      prevented. We conclude that the incorporation of human cardiac ECM hydrogel
      shifts and enhances the bioactivity of decellularized amniotic membrane,
      facilitating its use in future cardiac applications.

PMID- 29596385
TI  - Cigarette Waste in Popular Beaches in Thailand: High Densities that Demand
      Environmental Action.
AB  - Thailand, like all nations, has a responsibility to initiate environmental
      actions to preserve marine environments. Low- and middle-income countries face
      difficulties implementing feasible strategies to fulfill this ambitious goal. To
      contribute to the revitalization of Thailand's marine ecosystems, we investigated
      the level of tobacco product waste (TPW) on Thailand's public beaches. We
      conducted a cross-sectional observational survey at two popular public beaches.
      Research staff collected cigarette butts over two eight-hour days walking over a
      one-kilometer stretch of beach. We also compiled and analyzed data on butts
      collected from sieved sand at 11 popular beaches throughout Thailand's coast,
      with 10 samples of sieved sand collected per beach. Our survey at two beaches
      yielded 3067 butts in lounge areas, resulting in a mean butt density of 0.44/m2.
      At the 11 beaches, sieved sand samples yielded butt densities ranging from 0.25
      to 13.3/m2, with a mean butt density of 2.26/m2 (SD = 3.78). These densities show
      that TPW has become a serious problem along Thailand's coastline. Our findings
      are comparable with those in other countries. We report on government and civil
      society initiatives in Thailand that are beginning to address marine TPW. The
      solution will only happen when responsible parties, especially and primarily
      tobacco companies, undertake actions to eliminate TPW.

PMID- 29596383
TI  - TASK-3 Downregulation Triggers Cellular Senescence and Growth Inhibition in
      Breast Cancer Cell Lines.
AB  - TASK-3 potassium channels are believed to promote proliferation and survival of
      cancer cells, in part, by augmenting their resistance to both hypoxia and serum
      deprivation. While overexpression of TASK-3 is frequently observed in cancers,
      the understanding of its role and regulation during tumorigenesis remains
      incomplete. Here, we evaluated the effect of reducing the expression of TASK-3 in
      MDA-MB-231 and MCF-10F human mammary epithelial cell lines through small hairpin
      RNA (shRNA)-mediated knockdown. Our results show that knocking down TASK-3 in
      fully transformed MDA-MB-231 cells reduces proliferation, which was accompanied
      by an induction of cellular senescence and cell cycle arrest, with an
      upregulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27. In non
      tumorigenic MCF-10F cells, however, TASK-3 downregulation did not lead to
      senescence induction, although cell proliferation was impaired and an
      upregulation of CDK inhibitors was also evident. Our observations implicate TASK
      3 as a critical factor in cell cycle progression and corroborate its potential as
      a therapeutic target in breast cancer treatment.

PMID- 29596387
TI  - Robust Sliding Mode Control of PMSM Based on a Rapid Nonlinear Tracking
      Differentiator and Disturbance Observer.
AB  - Torque ripples caused by cogging torque, flux harmonics, and current measurement
      error seriously restrict the application of a permanent magnet synchronous motor
      (PMSM), which has been paid more and more attention for the use in inertial
      stabilized platforms. Sliding mode control (SMC), in parallel with the classical
      proportional integral (PI) controller, has a high advantage to suppress the
      torque ripples as its invariance to disturbances. However, since the high
      switching gain tends to cause chattering and it requires derivative of signals
      which is not readily obtainable without an acceleration signal sensor. Therefore,
      this paper proposes a robust SMC scheme based on a rapid nonlinear tracking
      differentiator (NTD) and a disturbance observer (DOB) to further improve the
      performance of the SMC. The NTD is employed to providing the derivative of the
      signal, and the DOB is utilized to estimate the system lumped disturbances,
      including parameter variations and external disturbances. On the one hand, DOB
      can compensate the robust SMC speed controller, it can reduce the chattering of
      SMC on the other hand. Experiments were carried out on an ARM and DSP-based
      platform. The obtained experimental results demonstrate that the robust SMC
      scheme has an improved performance with inertia stability and it exhibits a
      satisfactory anti-disturbance performance compared to the traditional methods.

PMID- 29596386
TI  - The Role of Serotonin during Skin Healing in Post-Thermal Injury.
AB  - Post-burn trauma significantly raises tissue serotonin concentration at the
      initial stages of injury, which leads us to investigate its possible role in post
      burn wound healing. Therefore, we planned this study to examine the role of
      serotonin in wound healing through in vitro and in vivo models of burn injuries.
      Results from in vitro analysis revealed that serotonin decreased apoptosis and
      increased cell survival significantly in human fibroblasts and neonatal
      keratinocytes. Cellular proliferation also increased significantly in both cell
      types. Moreover, serotonin stimulation significantly accelerated the cell
      migration, resulting in narrowing of the scratch zone in human neonatal
      keratinocytes and fibroblasts cultures. Whereas, fluoxetine (a selective
      serotonin reuptake inhibitor) and ketanserin (serotonin receptor 2A inhibitor)
      reversed these effects. Scald burn mice model (20% total body surface area)
      showed that endogenous serotonin improved wound healing process in control group,
      whereas fluoxetine and ketanserin treatments (disruptors of endogenous serotonin
      stimulation), resulted in poor reepithelization, bigger wound size and high alpha
      smooth muscle actin (alpha-SMA) count. All of these signs refer a prolonged
      differentiation state, which ultimately exhibits poor wound healing outcomes.
      Collectively, data showed that the endogenous serotonin pathway contributes to
      regulating the skin wound healing process. Hence, the results of this study
      signify the importance of serotonin as a potential therapeutic candidate for
      enhancing skin healing in burn patients.

PMID- 29596388
TI  - Genetic Variants in STAT3 Promoter Regions and Their Application in Molecular
      Breeding for Body Size Traits in Qinchuan Cattle.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays a critical role
      in leptin-mediated regulation of energy metabolism. This study investigated
      genetic variation in STAT3 promoter regions and verified their contribution to
      bovine body size traits. We first estimated the degree of conservation in STAT3,
      followed by measurements of its mRNA expression during fetal and adult stages of
      Qinchuan cattle. We then sequenced the STAT3 promoter region to determine genetic
      variants and evaluate their association with body size traits. From fetus to
      adult, STAT3 expression increased significantly in muscle, fat, heart, liver, and
      spleen tissues (p < 0.01), but decreased in the intestine, lung, and rumen (p <
      0.01). We identified and named five single nucleotide polymorphisms (SNPs): SNP1
      304A>C, SNP2-285G>A, SNP3-209A>C, SNP4-203A>G, and SNP5-188T>C. These five
      mutations fell significantly outside the Hardy-Weinberg equilibrium (HWE) (Chi
      squared test, p < 0.05) and significantly associated with body size traits (p <
      0.05). Individuals with haplotype H3H3 (CC-GG-CC-GG-CC) were larger in body size
      than other haplotypes. Therefore, variations in the STAT3 gene promoter regions,
      most notably haplotype H3H3, may benefit marker-assisted breeding of Qinchuan
      cattle.

PMID- 29596389
TI  - Enteric Virus Diversity Examined by Molecular Methods in Brazilian Poultry
      Flocks.
AB  - Enteric viruses play an important role in the Brazilian poultry industry due to
      the economic impact of resulting low yields of broilers, layers, and breeders.
      The most common enteric viruses affecting commercial flocks in Brazil include
      Fowl Adenovirus of group I (FAdV-I), Chicken Parvovirus (ChPV), Chicken
      Astrovirus (CAstV), Avian Nephritis Virus (ANV), Infectious Bronchitis Virus
      (IBV), Avian Reovirus (AReo), and Avian Rotavirus (ARtV). The aim of this study
      was to identify single and multiple infections using data obtained from 270
      samples from eleven Brazilian states, corresponding to the period between 2010
      and 2017. This was accompanied by an analysis of the relationship between the age
      of birds, clinical signs, and geographical distribution, using Polymerase Chain
      Reaction (PCR) and Reverse Transcription-PCR (RT-PCR) techniques. Twenty-five
      profiles of virus combinations were detected. Single infections were encountered
      in 86.3% of samples, and multiple infections were present in the remaining 13.7%.
      Both single and multiple infections affected all kinds of commercial chickens
      with digestive problems, stunting syndrome, decreases in egg and meat production,
      increased mortality, and respiratory signs. FAdV-I, ChPV, CAstV, ANV, and ARtV
      were mostly detected in young broilers, in contrast with IBV, which was detected
      in hens from one to greater than 51 weeks of age. These results exhibit the
      complexity of enteric diseases and the still poorly understood role of each
      pathogen as a unique etiological agent.

PMID- 29596390
TI  - The Effects of Plant-Derived Oleanolic Acid on Selected Parameters of Glucose
      Homeostasis in a Diet-Induced Pre-Diabetic Rat Model.
AB  - Prolonged exposure to high energy diets has been implicated in the development of
      pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus
      (T2DM). A combination of pharmacological and dietary interventions is used to
      prevent the progression of pre-diabetes to T2DM. However, poor patient compliance
      leads to negligence of the dietary intervention and thus reduced drug efficiency.
      Oleanolic acid (OA) has been reported to possess anti-diabetic effects in type 1
      diabetic rats. However, the effects of this compound on pre-diabetes have not yet
      been established. Consequently, this study sought to evaluate the effects OA on a
      diet-induced pre-diabetes rat model. Pre-diabetic male Sprague Dawley rats were
      treated with OA in both the presence and absence of dietary intervention for a
      period of 12 weeks. The administration of OA with and without dietary
      intervention resulted in significantly improved glucose homeostasis through
      reduced caloric intake, body weights, plasma ghrelin concentration and glycated
      haemoglobin by comparison to the pre-diabetic control. These results suggest that
      OA may be used to manage pre-diabetes as it was able to restore glucose
      homeostasis and prevented the progression to overt type 2 diabetes.

PMID- 29596392
TI  - Optimally Distributed Kalman Filtering with Data-Driven Communication.
AB  - For multisensor data fusion, distributed state estimation techniques that enable
      a local processing of sensor data are the means of choice in order to minimize
      storage and communication costs. In particular, a distributed implementation of
      the optimal Kalman filter has recently been developed. A significant disadvantage
      of this algorithm is that the fusion center needs access to each node so as to
      compute a consistent state estimate, which requires full communication each time
      an estimate is requested. In this article, different extensions of the optimally
      distributed Kalman filter are proposed that employ data-driven transmission
      schemes in order to reduce communication expenses. As a first relaxation of the
      full-rate communication scheme, it can be shown that each node only has to
      transmit every second time step without endangering consistency of the fusion
      result. Also, two data-driven algorithms are introduced that even allow for lower
      transmission rates, and bounds are derived to guarantee consistent fusion
      results. Simulations demonstrate that the data-driven distributed filtering
      schemes can outperform a centralized Kalman filter that requires each measurement
      to be sent to the center node.

PMID- 29596391
TI  - Screen-Printed Electrodes Modified with "Green" Metals for Electrochemical
      Stripping Analysis of Toxic Elements.
AB  - This work reviews the field of screen-printed electrodes (SPEs) modified with
      "green" metals for electrochemical stripping analysis of toxic elements.
      Electrochemical stripping analysis has been established as a useful trace
      analysis technique offering many advantages compared to competing optical
      techniques. Although mercury has been the preferred electrode material for
      stripping analysis, the toxicity of mercury and the associated legal requirements
      in its use and disposal have prompted research towards the development of "green"
      metals as alternative electrode materials. When combined with the screen-printing
      technology, such environment-friendly metals can lead to disposable sensors for
      trace metal analysis with excellent operational characteristics. This review
      focuses on SPEs modified with Au, Bi, Sb, and Sn for stripping analysis of toxic
      elements. Different modification approaches (electroplating, bulk modification,
      use of metal precursors, microengineering techniques) are considered and
      representative applications are described. A developing related field, namely
      biosensing based on stripping analysis of metallic nanoprobe labels, is also
      briefly mentioned.

PMID- 29596393
TI  - Object-Based Dense Matching Method for Maintaining Structure Characteristics of
      Linear Buildings.
AB  - In this paper, we proposed a novel object-based dense matching method specially
      for the high-precision disparity map of building objects in urban areas, which
      can maintain accurate object structure characteristics. The proposed framework
      mainly includes three stages. Firstly, an improved edge line extraction method is
      proposed for the edge segments to fit closely to building outlines. Secondly, a
      fusion method is proposed for the outlines under the constraint of straight
      lines, which can maintain the building structural attribute with parallel or
      vertical edges, which is very useful for the dense matching method. Finally, we
      proposed an edge constraint and outline compensation (ECAOC) dense matching
      method to maintain building object structural characteristics in the disparity
      map. In the proposed method, the improved edge lines are used to optimize
      matching search scope and matching template window, and the high-precision
      building outlines are used to compensate the shape feature of building objects.
      Our method can greatly increase the matching accuracy of building objects in
      urban areas, especially at building edges. For the outline extraction
      experiments, our fusion method verifies the superiority and robustness on
      panchromatic images of different satellites and different resolutions. For the
      dense matching experiments, our ECOAC method shows great advantages for matching
      accuracy of building objects in urban areas compared with three other methods.

PMID- 29596394
TI  - Real-Time Processing Library for Open-Source Hardware Biomedical Sensors.
AB  - Applications involving data acquisition from sensors need samples at a preset
      frequency rate, the filtering out of noise and/or analysis of certain frequency
      components. We propose a novel software architecture based on open-software
      hardware platforms which allows programmers to create data streams from input
      channels and easily implement filters and frequency analysis objects. The
      performances of the different classes given in the size of memory allocated and
      execution time (number of clock cycles) were analyzed in the low-cost platform
      Arduino Genuino. In addition, 11 people took part in an experiment in which they
      had to implement several exercises and complete a usability test. Sampling rates
      under 250 Hz (typical for many biomedical applications) makes it feasible to
      implement filters, sliding windows and Fourier analysis, operating in real time.
      Participants rated software usability at 70.2 out of 100 and the ease of use when
      implementing several signal processing applications was rated at just over 4.4
      out of 5. Participants showed their intention of using this software because it
      was percieved as useful and very easy to use. The performances of the library
      showed that it may be appropriate for implementing small biomedical real-time
      applications or for human movement monitoring, even in a simple open-source
      hardware device like Arduino Genuino. The general perception about this library
      is that it is easy to use and intuitive.

PMID- 29596395
TI  - Effect of Early-Life Treatment of Piglets with Long-Acting Ceftiofur on
      Colonization of Streptococcus suis Serotype 7 and Elicitation of Specific Humoral
      Immunity in a Farm Dealing with Streptococcal Diseases.
AB  - In newborn piglets treatment with long-acting ceftiofur is a common approach to
      reduce losses due to streptococcal diseases on farms, even if problems start
      after weaning. The purpose of this study was to examine the influence of a single
      early-life treatment on Streptococcus (S.) suis colonization, transmission,
      immunoreaction, and drug resistance over an observation period of 14 weeks. In a
      farm with a history of streptococcal disease and isolation of a S. suis cps 7
      mrp+, arcA+ isolate from diseased piglets, half of each litter was treated with a
      long-acting ceftiofur on day 1. S. suis-isolates were profiled and serum samples
      were tested for opsonizing antibodies. Treated and untreated pigs did not differ
      according to average daily weight gains, S. suis-isolation rates and level of
      opsonizing antibodies. Although the invasive cps 7 strain was not detected in a
      single piglet over 14 weeks, all animals developed bactericidal activity. No
      resistance to ceftiofur, but resistance to tetracyclins (100%), and
      trimethoprim/sulfamethoxazole (53%) was shown. Our results indicate that early
      treatment with ceftiofur does not prevent colonization and transmission of S.
      suis or the induction of bactericidal humoral immunity in nursery and fattening
      pigs. The necessity of continuous usage should be reconsidered.

PMID- 29596396
TI  - Smart Garment Fabrics to Enable Non-Contact Opto-Physiological Monitoring.
AB  - Imaging photoplethysmography (iPPG) is an emerging technology used to assess
      microcirculation and cardiovascular signs by collecting backscattered light from
      illuminated tissue using optical imaging sensors. The aim of this study was to
      study how effective smart garment fabrics could be capturing physiological signs
      in a non-contact mode. The present work demonstrates a feasible approach of,
      instead of using conventional high-power illumination sources, integrating a grid
      of surface-mounted light emitting diodes (LEDs) into cotton fabric to spotlight
      the region of interest (ROI). The green and the red LEDs (525 and 660 nm) placed
      on a small cotton substrate were used to locally illuminate palm skin in a dual
      wavelength iPPG setup, where the backscattered light is transmitted to a remote
      image sensor through the garment fabric. The results show that the illuminations
      from both wavelength LEDs can be used to extract heart rate (HR) reaching an
      accuracy of 90% compared to a contact PPG probe. Stretching the fabric over the
      skin surface alters the morphology of iPPG signals, demonstrating a significantly
      higher pulsatile amplitude in both channels of green and red illuminations. The
      skin compression by the fabric could be potentially utilised to enhance the
      penetration of illumination into cutaneous microvascular beds. The outcome could
      lead a new avenue of non-contact opto-physiological monitoring and assessment
      with functional garment fabrics.

PMID- 29596397
TI  - Vehicle Mode and Driving Activity Detection Based on Analyzing Sensor Data of
      Smartphones.
AB  - In this paper, we present a flexible combined system, namely the Vehicle mode
      driving Activity Detection System (VADS), that is capable of detecting either the
      current vehicle mode or the current driving activity of travelers. Our proposed
      system is designed to be lightweight in computation and very fast in response to
      the changes of travelers' vehicle modes or driving events. The vehicle mode
      detection module is responsible for recognizing both motorized vehicles, such as
      cars, buses, and motorbikes, and non-motorized ones, for instance, walking, and
      bikes. It relies only on accelerometer data in order to minimize the energy
      consumption of smartphones. By contrast, the driving activity detection module
      uses the data collected from the accelerometer, gyroscope, and magnetometer of a
      smartphone to detect various driving activities, i.e., stopping, going straight,
      turning left, and turning right. Furthermore, we propose a method to compute the
      optimized data window size and the optimized overlapping ratio for each vehicle
      mode and each driving event from the training datasets. The experimental results
      show that this strategy significantly increases the overall prediction accuracy.
      Additionally, numerous experiments are carried out to compare the impact of
      different feature sets (time domain features, frequency domain features, Hjorth
      features) as well as the impact of various classification algorithms (Random
      Forest, Naive Bayes, Decision tree J48, K Nearest Neighbor, Support Vector
      Machine) contributing to the prediction accuracy. Our system achieves an average
      accuracy of 98.33% in detecting the vehicle modes and an average accuracy of
      98.95% in recognizing the driving events of motorcyclists when using the Random
      Forest classifier and a feature set containing time domain features, frequency
      domain features, and Hjorth features. Moreover, on a public dataset of HTC
      company in New Taipei, Taiwan, our framework obtains the overall accuracy of
      97.33% that is considerably higher than that of the state-of the art.

PMID- 29596398
TI  - Ultra Uniform Pb0.865La0.09(Zr0.65Ti0.35)O3 Thin Films with Tunable Optical
      Properties Fabricated via Pulsed Laser Deposition.
AB  - Ferroelectric thin films have been utilized in a wide range of electronic and
      optical applications, in which their morphologies and properties can be
      inherently tuned by a qualitative control during growth. In this work, we
      demonstrate the evolution of the Pb0.865La0.09(Zr0.65Ti0.35)O3 (PLZT) thin films
      on MgO (200) with high uniformity and optimized optical property via the controls
      of the deposition temperatures and oxygen pressures. The perovskite phase can
      only be obtained at the deposition temperature above 700  degrees C and oxygen
      pressure over 50 Pa due to the improved crystallinity. Meanwhile, the surface
      morphologies gradually become smooth and compact owing to spontaneously increased
      nucleation sites with the elevated temperatures, and the crystallization of PLZT
      thin films also sensitively respond to the oxygen vacancies with the variation of
      oxygen pressures. Correspondingly, the refractive indices gradually develop with
      variations of the deposition temperatures and oxygen pressures resulted from the
      various slight loss, and the extinction coefficient for each sample is similarly
      near to zero due to the relatively smooth morphology. The resulting PLZT thin
      films exhibit the ferroelectricity, and the dielectric constant sensitively
      varies as a function of electric filed, which can be potentially applied in the
      electronic and optical applications.

PMID- 29596399
TI  - Bioinformatic Analysis of GLI1 and Related Signaling Pathways in Chemosensitivity
      of Gastric Cancer.
AB  - BACKGROUND This study assessed the prognostic value of GLI1 in gastric cancer and
      analyzed the possible GLI1-related signaling network in chemosensitivity.
      MATERIAL AND METHODS Bioinformatic data mining was performed by using data in the
      TCGA-Stomach Cancer (TCGA-STAD) and the Kaplan-Meier plotter. GLI1 co-expressed
      genes in TCGA-STAD were subjected to KEGG pathway analysis. The genes enriched in
      the KEGG pathways were further subjected to Protein-Protein Interaction (PPI)
      analysis. RESULTS In TCGA-STAD, high GLI1 gene/exon expression was associated
      with significantly worse survival (p=0.016 and 0.0023 respectively). In the
      Kaplan-Meier plotter, high GLI1 expression was associated with unfavorable
      overall survival (OS) (HR: 1.68, 95%CI: 1.42-2, p<0.0001) and first progression
      free survival (FPS) (HR: 1.72, 95%CI: 1.4-2.11, p<0.0001). In TCGA-STAD, 600 GLI1
      co-expressed genes were identified (absolute Pearson's r >=0.5). The most
      significant pathways were pathways in cancer (p=230.0E-12) and the Hedgehog
      signaling pathway (p=6.9E-9). PI3K-AKT pathway (p=17.0E-9) has the largest
      proportion of gene enrichment. Some GLI1 co-expressed genes in the PI3K-AKT
      pathway are central nodes in the PPI network and also play important roles in
      chemosensitivity of gastric cancer. Nevertheless, the mechanisms underlying their
      co-expression are still largely unexplored. CONCLUSIONS High GLI1 expression is
      associated with unfavorable OS and FPS in patients with gastric cancer. As a
      member of the Hedgehog signaling pathway, GLI1 co-expressed genes are also
      largely enriched in PI3K/AKT pathway in gastric cancer, which is closely related
      to chemoresistance. The underlying mechanisms are still largely unexplored and
      need further study.

PMID- 29596401
TI  - QuickStats: Age-Adjusted Death Rates* for Drug Overdose,? by Race/Ethnicity -
      National Vital Statistics System, United States, 2015-2016.

PMID- 29596400
TI  - Trends in Diabetic Ketoacidosis Hospitalizations and In-Hospital Mortality -
      United States, 2000-2014.
AB  - Diabetes is a common chronic condition and as of 2015, approximately 30 million
      persons in the United States had diabetes (23 million with diagnosed and 7
      million with undiagnosed) (1). Diabetic ketoacidosis (DKA) is a life-threatening
      but preventable complication of diabetes characterized by uncontrolled
      hyperglycemia (>250 mg/dL), metabolic acidosis, and increased ketone
      concentration that occurs most frequently in persons with type 1 diabetes (2).
      CDC's United States Diabetes Surveillance System* (USDSS) indicated an increase
      in hospitalization rates for DKA during 2009-2014, most notably in persons aged
      <45 years. To explore this finding, 2000-2014 data from the Agency for Healthcare
      Research and Quality's National Inpatient Sample (NIS)? were assembled to
      calculate trends in DKA hospitalization rates and in-hospital case-fatality
      rates. Overall, age-adjusted DKA hospitalization rates decreased slightly from
      2000 to 2009, then reversed direction, steadily increasing from 2009 to 2014 at
      an average annual rate of 6.3%. In-hospital case-fatality rates declined
      consistently during the study period from 1.1% to 0.4%. Better understanding the
      causes of this increasing trend in DKA hospitalizations and decreasing trend in
      in-hospital case-fatality through further exploration using multiple data sources
      will facilitate the targeting of prevention efforts.

PMID- 29596402
TI  - Prevalence of Diagnosed Diabetes in Adults by Diabetes Type - United States,
      2016.
AB  - Currently 23 million U.S. adults have been diagnosed with diabetes (1). The two
      most common forms of diabetes are type 1 and type 2. Type 1 diabetes results from
      the autoimmune destruction of the pancreas's beta cells, which produce insulin.
      Persons with type 1 diabetes require insulin for survival; insulin may be given
      as a daily shot or continuously with an insulin pump (2). Type 2 diabetes is
      mainly caused by a combination of insulin resistance and relative insulin
      deficiency (3). A small proportion of diabetes cases might be types other than
      type 1 or type 2, such as maturity-onset diabetes of the young or latent
      autoimmune diabetes in adults (3). Although the majority of prevalent cases of
      type 1 and type 2 diabetes are in adults, national data on the prevalence of type
      1 and type 2 in the U.S. adult population are sparse, in part because of the
      previous difficulty in classifying diabetes by type in surveys (2,4,5). In 2016,
      supplemental questions to help distinguish diabetes type were added to the
      National Health Interview Survey (NHIS) (6). This study used NHIS data from 2016
      to estimate the prevalence of diagnosed diabetes among adults by primary type.
      Overall, based on self-reported type and current insulin use, 0.55% of U.S.
      adults had diagnosed type 1 diabetes, representing 1.3 million adults; 8.6% had
      diagnosed type 2 diabetes, representing 21.0 million adults. Of all diagnosed
      cases, 5.8% were type 1 diabetes, and 90.9% were type 2 diabetes; the remaining
      3.3% of cases were other types of diabetes. Understanding the prevalence of
      diagnosed diabetes by type is important for monitoring trends, planning public
      health responses, assessing the burden of disease for education and management
      programs, and prioritizing national plans for future type-specific health
      services.

PMID- 29596404
TI  - Erratum: Vol. 67, No. 7.

PMID- 29596403
TI  - Two Cases of Meningococcal Disease in One Family Separated by an Extended Period 
      Colorado, 2015-2016.
AB  - On April 26, 2015, a case of meningococcal disease in a woman aged 75 years was
      reported to the Colorado Department of Public Health and Environment (CDPHE). As
      part of routine public health investigation and control activities, all seven
      family contacts of the patient were advised to receive appropriate postexposure
      prophylaxis (PEP) to eradicate nasopharyngeal carriage of meningococci and
      prevent secondary disease (1), although it is not known whether the family
      contacts complied with PEP recommendations. Fifteen months later, on June 6,
      2016, CDPHE was notified that the grandchild of the first patient, a male infant
      aged 3 months who lived with the first patient, also had meningococcal disease.
      The infant's immediate family members (parents and one sibling) were among family
      contacts for whom PEP was recommended in 2015. Neisseria meningitidis isolates
      from both patients were found to be serogroup C at the CDPHE laboratory. Whole
      genome sequence (WGS) analysis at CDC found that both isolates had the same
      sequence type, indicating close genetic relatedness. These cases represent a
      possible instance of meningococcal disease transmission within a family, despite
      appropriate PEP recommendations and with a long interval between cases.

PMID- 29596405
TI  - Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States,
      2015-2016.
AB  - During 1999-2015, 568,699 persons died from drug overdoses in the United States.*
      Drug overdose deaths in the United States increased 11.4% from 2014 to 2015
      resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an
      opioid. The largest rate increases from 2014 to 2015 occurred among deaths
      involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1).
      Because of demographic and geographic variations in overdose deaths involving
      different drugs (2,3),? CDC examined age-adjusted death rates for overdoses
      involving all opioids, opioid subcategories (i.e., prescription opioids, heroin,
      and synthetic opioids),S cocaine, and psychostimulants with abuse potential
      (psychostimulants) by demographics, urbanization levels, and in 31 states and the
      District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249
      (66.4%) involved an opioid.  From 2015 to 2016, deaths increased across all drug
      categories examined. The largest overall rate increases occurred among deaths
      involving cocaine (52.4%) and synthetic opioids (100%), likely driven by
      illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across
      demographics, urbanization levels, and states and DC. The opioid overdose
      epidemic in the United States continues to worsen. A multifaceted approach, with
      faster and more comprehensive surveillance, is needed to track emerging threats
      to prevent and respond to the overdose epidemic through naloxone availability,
      safe prescribing practices, harm-reduction services, linkage into treatment, and
      more collaboration between public health and public safety agencies.

PMID- 29596407
TI  - Notes from the Field: Fatalities Associated with Human Adenovirus Type 7 at a
      Substance Abuse Rehabilitation Facility - New Jersey, 2017.

PMID- 29596406
TI  - Heart Disease Death Rates Among Blacks and Whites Aged >=35 Years - United
      States, 1968-2015.
AB  - PROBLEM/CONDITION: Heart disease is the leading cause of death in the United
      States. In 2015, heart disease accounted for approximately 630,000 deaths,
      representing one in four deaths in the United States. Although heart disease
      death rates decreased 68% for the total population from 1968 to 2015, marked
      disparities in decreases exist by race and state. PERIOD COVERED: 1968-2015.
      DESCRIPTION OF SYSTEM: The National Vital Statistics System (NVSS) data on deaths
      in the United States were abstracted for heart disease using diagnosis codes from
      the eighth, ninth, and tenth revisions of the International Classification of
      Diseases (ICD-8, ICD-9, and ICD-10) for 1968-2015. Population estimates were
      obtained from NVSS files. National and state-specific heart disease death rates
      for the total population and by race for adults aged >=35 years were calculated
      for 1968-2015. National and state-specific black-white heart disease mortality
      ratios also were calculated. Death rates were age standardized to the 2000 U.S.
      standard population. Joinpoint regression was used to perform time trend
      analyses. RESULTS: From 1968 to 2015, heart disease death rates decreased for the
      total U.S. population among adults aged >=35 years, from 1,034.5 to 327.2 per
      100,000 population, respectively, with variations in the magnitude of decreases
      by race and state. Rates decreased for the total population an average of 2.4%
      per year, with greater average decreases among whites (2.4% per year) than blacks
      (2.2% per year). At the national level, heart disease death rates for blacks and
      whites were similar at the start of the study period (1968) but began to diverge
      in the late 1970s, when rates for blacks plateaued while rates for whites
      continued to decrease. Heart disease death rates among blacks remained higher
      than among whites for the remainder of the study period. Nationwide, the black
      white ratio of heart disease death rates increased from 1.04 in 1968 to 1.21 in
      2015, with large increases occurring during the 1970s and 1980s followed by small
      but steady increases until approximately 2005. Since 2005, modest decreases have
      occurred in the black-white ratio of heart disease death rates at the national
      level. The majority of states had increases in black-white mortality ratios from
      1968 to 2015. The number of states with black-white mortality ratios >1 increased
      from 16 (40%) to 27 (67.5%). INTERPRETATION: Although heart disease death rates
      decreased both for blacks and whites from 1968 to 2015, substantial differences
      in decreases were found by race and state. At the national level and in most
      states, blacks experienced smaller decreases in heart disease death rates than
      whites for the majority of the period. Overall, the black-white disparity in
      heart disease death rates increased from 1968 to 2005, with a modest decrease
      from 2005 to 2015. PUBLIC HEALTH ACTION: Since 1968, substantial increases have
      occurred in black-white disparities of heart disease death rates in the United
      States at the national level and in many states. These increases appear to be due
      to faster decreases in heart disease death rates for whites than blacks,
      particularly from the late 1970s until the mid-2000s. Despite modest decreases in
      black-white disparities at the national level since 2005, in 2015, heart disease
      death rates were 21% higher among blacks than among whites. This study
      demonstrates the use of NVSS data to conduct surveillance of heart disease death
      rates by race and of black-white disparities in heart disease death rates.
      Continued surveillance of temporal trends in heart disease death rates by race
      can provide valuable information to policy makers and public health practitioners
      working to reduce heart disease death rates both for blacks and whites and
      disparities between blacks and whites.

PMID- 29596408
TI  - Publisher correction: Functional characterization of a multi-cancer risk locus on
      chr5p15.33 reveals regulation of TERT by ZNF148.
AB  - This corrects the article DOI: 10.1038/ncomms15034.

PMID- 29596409
TI  - Distinct inflammatory profile underlies pathological increases in creatinine
      levels associated with Plasmodium vivax malaria clinical severity.
AB  - BACKGROUND: Although Plasmodium vivax infection is a frequent cause of malaria
      worldwide, severe presentations have been more regularly described only in recent
      years. In this setting, despite clinical descriptions of multi-organ involvement,
      data associating it with kidney dysfunction are relatively scarce. Here, renal
      dysfunction is retrospectively analyzed in a large cohort of vivax malaria
      patients with an attempt to dissect its association with disease severity and
      mortality, and to determine the role of inflammation in its progression. METHODS:
      A retrospective analysis of a databank containing 572 individuals from the
      Brazilian Amazon, including 179 patients with P. vivax monoinfection (161
      symptomatic malaria, 12 severe non-lethal malaria, and 6 severe lethal disease)
      and 165 healthy controls, was performed. Data on levels of cytokines, chemokines,
      C-reactive protein (CRP), fibrinogen, creatinine, hepatic enzymes, bilirubin
      levels, free heme, and haptoglobin were analyzed to depict and compare profiles
      from patients per creatinine levels. RESULTS: Elevated creatinine levels were
      found predominantly in women. Vivax malaria severity was highly associated with
      abnormal creatinine increases, and nonsurvivors presented the highest values of
      serum creatinine. Indication of kidney dysfunction was not associated with
      parasitemia levels. IFN-gamma/IL-10 ratio and CRP values marked the immune
      biosignature of vivax malaria patients, and could distinguish subjects with
      elevated creatinine levels who did not survive from those who did. Patients with
      elevated serum creatinine or severe vivax malaria displayed indication of
      cholestasis. Biomarkers of hemolysis did not follow increases in serum
      creatinine. CONCLUSION: These findings reinforce the hypothesis that renal
      dysfunction is a key component in P. vivax malaria associated with clinical
      severity and mortality, possibly through intense inflammation and immune
      imbalance. Our study argues for systematic evaluation of kidney function as part
      of the clinical assessment in vivax malaria patients, and warrants additional
      studies in experimental models for further mechanism investigations.

PMID- 29596410
TI  - Identifying off-target effects of etomoxir reveals that carnitine
      palmitoyltransferase I is essential for cancer cell proliferation independent of
      beta-oxidation.
AB  - It has been suggested that some cancer cells rely upon fatty acid oxidation (FAO)
      for energy. Here we show that when FAO was reduced approximately 90% by
      pharmacological inhibition of carnitine palmitoyltransferase I (CPT1) with low
      concentrations of etomoxir, the proliferation rate of various cancer cells was
      unaffected. Efforts to pharmacologically inhibit FAO more than 90% revealed that
      high concentrations of etomoxir (200 MUM) have an off-target effect of inhibiting
      complex I of the electron transport chain. Surprisingly, however, when FAO was
      reduced further by genetic knockdown of CPT1, the proliferation rate of these
      same cells decreased nearly 2-fold and could not be restored by acetate or
      octanoic acid supplementation. Moreover, CPT1 knockdowns had altered
      mitochondrial morphology and impaired mitochondrial coupling, whereas cells in
      which CPT1 had been approximately 90% inhibited by etomoxir did not. Lipidomic
      profiling of mitochondria isolated from CPT1 knockdowns showed depleted
      concentrations of complex structural and signaling lipids. Additionally,
      expression of a catalytically dead CPT1 in CPT1 knockdowns did not restore
      mitochondrial coupling. Taken together, these results suggest that transport of
      at least some long-chain fatty acids into the mitochondria by CPT1 may be
      required for anabolic processes that support healthy mitochondrial function and
      cancer cell proliferation independent of FAO.

PMID- 29596411
TI  - Common occurrence of Cryptosporidium hominis in asymptomatic and symptomatic
      calves in France.
AB  - BACKGROUND: Cryptosporidium spp. infections are the most frequent parasitic cause
      of diarrhea in humans and cattle. However, asymptomatic cases are less often
      documented than symptomatic cases or cases with experimentally infected animals.
      Cryptosporidium (C.) hominis infection accounts for the majority of pediatric
      cases in several countries, while C. parvum is a major cause of diarrhea in
      neonatal calves. In cattle Cryptosporidium spp. infection can be caused by C.
      parvum, C. bovis, C.andersoni and C. ryanae, and recently, reports of cattle
      cases of C. hominis cryptosporidiosis cases suggest that the presence of C.
      hominis in calves was previously underestimated. METHODOLOGY/PRINCIPAL FINDINGS:
      From February to November 2015, Cryptosporidium spp. infected calves were
      detected in 29/44 randomly included farms from 5 geographic regions of France. C.
      hominis and C. parvum were found in 12/44 and 26/44 farms, respectively with
      higher C. hominis prevalence in the western region. In 9 farms, both C. parvum
      and C. hominis were detected. Eighty-six of 412 (73/342 asymptomatic and 13/70
      symptomatic) one to nine-week-old calves shed C. hominis or C. parvum oocysts (15
      and 71 calves, respectively), with no mixed infection detected. The predominant
      C. hominis IbA9G3 genotype was present in all regions, and more frequent in the
      western region. An incompletely characterized Ib, and the IbA13G3, IbA9G2 and
      IbA14G2 genotypes were present only in the western region. For C. parvum, the
      most frequent genotype was IIaA16G3R1 with no geographic clustering. Most C.
      hominis infected calves were asymptomatic, with some exceptions of IbA9G2 and
      IbA9G3 isolates, while C. parvum IIaA16G3R1 was associated with symptoms.
      CONCLUSIONS/SIGNIFICANCE: Present results indicate for the first time that in
      several geographic regions of France, C. hominis was present in about one fifth
      of both asymptomatic and symptomatic infected calves, with isolated genotypes
      likely associated with human infection. Further investigations are aimed at
      documenting direct or indirect transmissions between livestock and humans.

PMID- 29596412
TI  - Development and evaluation of antibody-capture immunoassays for detection of
      Lassa virus nucleoprotein-specific immunoglobulin M and G.
AB  - BACKGROUND: The classical method for detection of Lassa virus-specific antibodies
      is the immunofluorescence assay (IFA) using virus-infected cells as antigen.
      However, IFA requires laboratories of biosafety level 4 for assay production and
      an experienced investigator to interpret the fluorescence signals. Therefore, we
      aimed to establish and evaluate enzyme-linked immunosorbent assays (ELISA) using
      recombinant Lassa virus nucleoprotein (NP) as antigen. METHODOLOGY/PRINCIPAL
      FINDINGS: The IgM ELISA is based on capturing IgM antibodies using anti-IgM, and
      the IgG ELISA is based on capturing IgG antibody-antigen complexes using
      rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation
      was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic
      (Ghana and Germany) areas. Using the IFA as reference method, we observed 91.5
      94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific
      antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to
      hospital in an endemic area revealed a clinical sensitivity for the stand-alone
      IgM ELISA of 31% (95% CI 25-37) and for combined IgM/IgG detection of 26% (95% CI
      21-32) compared to RT-PCR. The specificity of IgM and IgG ELISA was estimated at
      96% (95% CI 93-98) and 100% (95% CI 99-100), respectively, in non-Lassa fever
      patients from non-endemic areas. In patients who seroconverted during follow-up,
      Lassa virus-specific IgM and IgG developed simultaneously rather than
      sequentially. Consistent with this finding, isolated IgM reactivity, i.e. IgM in
      the absence of IgG, had no diagnostic value. CONCLUSIONS/SIGNIFICANCE: The ELISAs
      are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they
      are of value in diagnosing patients at later stage. The IgG ELISA may be useful
      for epidemiological studies and clinical trials due its high specificity, and the
      higher throughput rate and easier operation compared to IFA.

PMID- 29596413
TI  - Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically
      distant yeast species activates the general amino acid control pathway.
AB  - Modification defects in the tRNA anticodon loop often impair yeast growth and
      cause human disease. In the budding yeast Saccharomyces cerevisiae and the
      phylogenetically distant fission yeast Schizosaccharomyces pombe, trm7Delta
      mutants grow poorly due to lack of 2'-O-methylation of C32 and G34 in the tRNAPhe
      anticodon loop, and lesions in the human TRM7 homolog FTSJ1 cause non-syndromic X
      linked intellectual disability (NSXLID). However, it is unclear why trm7Delta
      mutants grow poorly. We show here that despite the fact that S. cerevisiae
      trm7Delta mutants had no detectable tRNAPhe charging defect in rich media, the
      cells constitutively activated a robust general amino acid control (GAAC)
      response, acting through Gcn2, which senses uncharged tRNA. Consistent with
      reduced available charged tRNAPhe, the trm7Delta growth defect was suppressed by
      spontaneous mutations in phenylalanyl-tRNA synthetase (PheRS) or in the pol III
      negative regulator MAF1, and by overexpression of tRNAPhe, PheRS, or EF-1A; all
      of these also reduced GAAC activation. Genetic analysis also demonstrated that
      the trm7Delta growth defect was due to the constitutive robust GAAC activation as
      well as to the reduced available charged tRNAPhe. Robust GAAC activation was not
      observed with several other anticodon loop modification mutants. Analysis of S.
      pombe trm7 mutants led to similar observations. S. pombe Trm7 depletion also
      resulted in no observable tRNAPhe charging defect and a robust GAAC response, and
      suppressors mapped to PheRS and reduced GAAC activation. We speculate that GAAC
      activation is widely conserved in trm7 mutants in eukaryotes, including
      metazoans, and might play a role in FTSJ1-mediated NSXLID.

PMID- 29596415
TI  - Assessing scientists for hiring, promotion, and tenure.
AB  - Assessment of researchers is necessary for decisions of hiring, promotion, and
      tenure. A burgeoning number of scientific leaders believe the current system of
      faculty incentives and rewards is misaligned with the needs of society and
      disconnected from the evidence about the causes of the reproducibility crisis and
      suboptimal quality of the scientific publication record. To address this issue,
      particularly for the clinical and life sciences, we convened a 22-member expert
      panel workshop in Washington, DC, in January 2017. Twenty-two academic leaders,
      funders, and scientists participated in the meeting. As background for the
      meeting, we completed a selective literature review of 22 key documents
      critiquing the current incentive system. From each document, we extracted how the
      authors perceived the problems of assessing science and scientists, the
      unintended consequences of maintaining the status quo for assessing scientists,
      and details of their proposed solutions. The resulting table was used as a seed
      for participant discussion. This resulted in six principles for assessing
      scientists and associated research and policy implications. We hope the content
      of this paper will serve as a basis for establishing best practices and
      redesigning the current approaches to assessing scientists by the many players
      involved in that process.

PMID- 29596416
TI  - Eleven quick tips for architecting biomedical informatics workflows with cloud
      computing.
AB  - Cloud computing has revolutionized the development and operations of hardware and
      software across diverse technological arenas, yet academic biomedical research
      has lagged behind despite the numerous and weighty advantages that cloud
      computing offers. Biomedical researchers who embrace cloud computing can reap
      rewards in cost reduction, decreased development and maintenance workload,
      increased reproducibility, ease of sharing data and software, enhanced security,
      horizontal and vertical scalability, high availability, a thriving technology
      partner ecosystem, and much more. Despite these advantages that cloud-based
      workflows offer, the majority of scientific software developed in academia does
      not utilize cloud computing and must be migrated to the cloud by the user. In
      this article, we present 11 quick tips for architecting biomedical informatics
      workflows on compute clouds, distilling knowledge gained from experience
      developing, operating, maintaining, and distributing software and virtualized
      appliances on the world's largest cloud. Researchers who follow these tips stand
      to benefit immediately by migrating their workflows to cloud computing and
      embracing the paradigm of abstraction.

PMID- 29596414
TI  - Complete chloroplast genome sequence and comparative analysis of loblolly pine
      (Pinus taeda L.) with related species.
AB  - Pinaceae, the largest family of conifers, has a diversified organization of
      chloroplast (cp) genomes with two typical highly reduced inverted repeats (IRs).
      In the current study, we determined the complete sequence of the cp genome of an
      economically and ecologically important conifer tree, the loblolly pine (Pinus
      taeda L.), using Illumina paired-end sequencing and compared the sequence with
      those of other pine species. The results revealed a genome size of 121,531 base
      pairs (bp) containing a pair of 830-bp IR regions, distinguished by a small
      single copy (42,258 bp) and large single copy (77,614 bp) region. The chloroplast
      genome of P. taeda encodes 120 genes, comprising 81 protein-coding genes, four
      ribosomal RNA genes, and 35 tRNA genes, with 151 randomly distributed
      microsatellites. Approximately 6 palindromic, 34 forward, and 22 tandem repeats
      were found in the P. taeda cp genome. Whole cp genome comparison with those of
      other Pinus species exhibited an overall high degree of sequence similarity, with
      some divergence in intergenic spacers. Higher and lower numbers of indels and
      single-nucleotide polymorphism substitutions were observed relative to P.
      contorta and P. monophylla, respectively. Phylogenomic analyses based on the
      complete genome sequence revealed that 60 shared genes generated trees with the
      same topologies, and P. taeda was closely related to P. contorta in the subgenus
      Pinus. Thus, the complete P. taeda genome provided valuable resources for
      population and evolutionary studies of gymnosperms and can be used to identify
      related species.

PMID- 29596417
TI  - Eleven quick tips for running an interdisciplinary short course for new graduate
      students.
AB  - Quantitative reasoning and techniques are increasingly ubiquitous across the life
      sciences. However, new graduate researchers with a biology background are often
      not equipped with the skills that are required to utilize such techniques
      correctly and efficiently. In parallel, there are increasing numbers of
      engineers, mathematicians, and physical scientists interested in studying
      problems in biology with only basic knowledge of this field. Students from such
      varied backgrounds can struggle to engage proactively together to tackle problems
      in biology. There is therefore a need to establish bridges between those
      disciplines. It is our proposal that the beginning of graduate school is the
      appropriate time to initiate those bridges through an interdisciplinary short
      course. We have instigated an intensive 10-day course that brought together new
      graduate students in the life sciences from across departments within the
      National University of Singapore. The course aimed at introducing biological
      problems as well as some of the quantitative approaches commonly used when
      tackling those problems. We have run the course for three years with over 100
      students attending. Building on this experience, we share 11 quick tips on how to
      run such an effective, interdisciplinary short course for new graduate students
      in the biosciences.

PMID- 29596419
TI  - Correction: Early postnatal exposure to isoflurane causes cognitive deficits and
      disrupts development of newborn hippocampal neurons via activation of the mTOR
      pathway.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.2001246.].

PMID- 29596418
TI  - Accessing microfluidics through feature-based design software for 3D printing.
AB  - Additive manufacturing has been a cornerstone of the product development pipeline
      for decades, playing an essential role in the creation of both functional and
      cosmetic prototypes. In recent years, the prospects for distributed and open
      source manufacturing have grown tremendously. This growth has been enabled by an
      expanding library of printable materials, low-cost printers, and communities
      dedicated to platform development. The microfluidics community has embraced this
      opportunity to integrate 3D printing into the suite of manufacturing strategies
      used to create novel fluidic architectures. The rapid turnaround time and low
      cost to implement these strategies in the lab makes 3D printing an attractive
      alternative to conventional micro- and nanofabrication techniques. In this work,
      the production of multiple microfluidic architectures using a hybrid 3D printing
      soft lithography approach is demonstrated and shown to enable rapid device
      fabrication with channel dimensions that take advantage of laminar flow
      characteristics. The fabrication process outlined here is underpinned by the
      implementation of custom design software with an integrated slicer program that
      replaces less intuitive computer aided design and slicer software tools. Devices
      are designed in the program by assembling parameterized microfluidic building
      blocks. The fabrication process and flow control within 3D printed devices were
      demonstrated with a gradient generator and two droplet generator designs. Precise
      control over the printing process allowed 3D microfluidics to be printed in a
      single step by extruding bridge structures to 'jump-over' channels in the same
      plane. This strategy was shown to integrate with conventional nanofabrication
      strategies to simplify the operation of a platform that incorporates both
      nanoscale features and 3D printed microfluidics.

PMID- 29596420
TI  - Isolated iliac cryptococcosis in an immunocompetent patient.

PMID- 29596421
TI  - Asgard archaea are the closest prokaryotic relatives of eukaryotes.

PMID- 29596422
TI  - Calculation for tensile strength and fracture toughness of granite with three
      kinds of grain sizes using three-point-bending test.
AB  - Tensile strength and fracture toughness, important parameters of the rock for
      engineering applications are difficult to measure. Thus this paper selected three
      kinds of granite samples (grain sizes = 1.01mm, 2.12mm and 3mm), used the
      combined experiments of physical and numerical simulation (RFPA-DIP version) to
      conduct three-point-bending (3-p-b) tests with different notches and introduced
      the acoustic emission monitor system to analyze the fracture mechanism around the
      notch tips. To study the effects of grain size on the tensile strength and
      toughness of rock samples, a modified fracture model was established linking
      fictitious crack to the grain size so that the microstructure of the specimens
      and fictitious crack growth can be considered together. The fractal method was
      introduced to represent microstructure of three kinds of granites and used to
      determine the length of fictitious crack. It is a simple and novel method to
      calculate the tensile strength and fracture toughness directly. Finally, the
      theoretical model was verified by the comparison to the numerical experiments by
      calculating the nominal strength sigman and maximum loads Pmax.

PMID- 29596423
TI  - SARNAclust: Semi-automatic detection of RNA protein binding motifs from
      immunoprecipitation data.
AB  - RNA-protein binding is critical to gene regulation, controlling fundamental
      processes including splicing, translation, localization and stability, and
      aberrant RNA-protein interactions are known to play a role in a wide variety of
      diseases. However, molecular understanding of RNA-protein interactions remains
      limited; in particular, identification of RNA motifs that bind proteins has long
      been challenging, especially when such motifs depend on both sequence and
      structure. Moreover, although RNA binding proteins (RBPs) often contain more than
      one binding domain, algorithms capable of identifying more than one binding motif
      simultaneously have not been developed. In this paper we present a novel pipeline
      to determine binding peaks in crosslinking immunoprecipitation (CLIP) data, to
      discover multiple possible RNA sequence/structure motifs among them, and to
      experimentally validate such motifs. At the core is a new semi-automatic
      algorithm SARNAclust, the first unsupervised method to identify and deconvolve
      multiple sequence/structure motifs simultaneously. SARNAclust computes similarity
      between sequence/structure objects using a graph kernel, providing the ability to
      isolate the impact of specific features through the bulge graph formalism.
      Application of SARNAclust to synthetic data shows its capability of clustering 5
      motifs at once with a V-measure value of over 0.95, while GraphClust achieves
      only a V-measure of 0.083 and RNAcontext cannot detect any of the motifs. When
      applied to existing eCLIP sets, SARNAclust finds known motifs for SLBP and HNRNPC
      and novel motifs for several other RBPs such as AGGF1, AKAP8L and ILF3. We
      demonstrate an experimental validation protocol, a targeted Bind-n-Seq-like high
      throughput sequencing approach that relies on RNA inverse folding for oligo pool
      design, that can validate the components within the SLBP motif. Finally, we use
      this protocol to experimentally interrogate the SARNAclust motif predictions for
      protein ILF3. Our results support a newly identified partially double-stranded
      UUUUUGAGA motif similar to that known for the splicing factor HNRNPC.

PMID- 29596424
TI  - Germ cells in the teleost fish medaka have an inherent feminizing effect.
AB  - AUTHOR SUMMARY: Germ cells are the only cells that can transfer genetic materials
      to the next generation via the sperm or egg. However, recent analyses in teleosts
      revealed another essential role of germ cells: feminizing the gonads. In our
      study, medaka mutants in which gametogenesis was blocked at specific stages
      provides the novel view that the feminizing effect of germ cells occurs in
      parallel with other reproductive elements, such as meiosis, the sexual fate
      decision of germ cells, and gametogenesis. Germ cells in medaka may have a
      potential to feminize gonads at the moment they have developed.

PMID- 29596425
TI  - The 'COmorBidity in Relation to AIDS' (COBRA) cohort: Design, methods and
      participant characteristics.
AB  - BACKGROUND: Persons living with HIV on combination antiretroviral therapy (cART)
      may be at increased risk of the development of age-associated non-communicable
      comorbidities (AANCC) at relatively young age. It has therefore been hypothesised
      that such individuals, despite effective cART, may be prone to accelerated aging.
      OBJECTIVE: The COmorBidity in Relation to AIDS (COBRA) cohort study was designed
      to investigate the potential causal link between HIV and AANCC, amongst others,
      in a cohort of middle-aged individuals with HIV with sustained viral suppression
      on cART and otherwise comparable HIV-negative controls. METHODS: Longitudinal
      cohort study of HIV-positive subjects >=45 years of age, with sustained HIV
      suppression on cART recruited from two large European HIV treatment centres and
      similarly-aged HIV-negative controls recruited from sexual health centres and
      targeted community groups. Both HIV-positive and HIV-negative subjects were
      assessed at study entry and again at follow-up after 2 years. RESULTS: Of the 134
      HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited,
      93% were male, 88% of white ethnicity and 86% were men who have sex with men
      (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52,
      64) and 92% were male, 97% of white ethnicity and 80% were MSM. CONCLUSIONS: The
      results from the COBRA study will be a significant resource to understand the
      link between HIV and AANCC and the pathogenic mechanisms underlying this link.
      COBRA will inform future development of novel prognostic tools for earlier
      diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may
      prevent AANCC.

PMID- 29596426
TI  - Quantifying the impact of scholarly papers based on higher-order weighted
      citations.
AB  - Quantifying the impact of a scholarly paper is of great significance, yet the
      effect of geographical distance of cited papers has not been explored. In this
      paper, we examine 30,596 papers published in Physical Review C, and identify the
      relationship between citations and geographical distances between author
      affiliations. Subsequently, a relative citation weight is applied to assess the
      impact of a scholarly paper. A higher-order weighted quantum PageRank algorithm
      is also developed to address the behavior of multiple step citation flow.
      Capturing the citation dynamics with higher-order dependencies reveals the actual
      impact of papers, including necessary self-citations that are sometimes excluded
      in prior studies. Quantum PageRank is utilized in this paper to help
      differentiating nodes whose PageRank values are identical.

PMID- 29596428
TI  - Asgard archaea do not close the debate about the universal tree of life topology.

PMID- 29596427
TI  - Taking a bite out of nutrition and arbovirus infection.
AB  - Nutrition is a key factor in host-pathogen defense. Malnutrition can increase
      both host susceptibility and severity of infection through a number of pathways,
      and infection itself can promote nutritional deterioration and further
      susceptibility. Nutritional status can also strongly influence response to
      vaccination or therapeutic pharmaceuticals. Arthropod-borne viruses (arboviruses)
      have a long history of infecting humans, resulting in regular pandemics as well
      as an increasing frequency of autochthonous transmission. Interestingly, aside
      from host-related factors, nutrition could also play a role in the competence of
      vectors required for transmission of these viruses. Nutritional status of the
      host and vector could even influence viral evolution itself. Therefore, it is
      vital to understand the role of nutrition in the arbovirus lifecycle. This Review
      will focus on nutritional factors that could influence susceptibility and
      severity of infection in the host, response to prophylactic and therapeutic
      strategies, vector competence, and viral evolution.

PMID- 29596429
TI  - Age-related collagen turnover of the interstitial matrix and basement membrane:
      Implications of age- and sex-dependent remodeling of the extracellular matrix.
AB  - The extracellular matrix (ECM) plays a vital role in maintaining normal tissue
      function. Collagens are major components of the ECM and there is a tight
      equilibrium between degradation and formation of these proteins ensuring tissue
      health and homeostasis. As a consequence of tissue turnover, small collagen
      fragments are released into the circulation, which act as important biomarkers in
      the study of certain tissue-related remodeling factors in health and disease. The
      aim of this study was to establish an age-related collagen turnover profile of
      the main collagens of the interstitial matrix (type I and III collagen) and
      basement membrane (type IV collagen) in healthy men and women. By using well
      characterized competitive ELISA-assays, we assessed specific fragments of
      degraded (C1M, C3M, C4M) and formed (PINP, Pro-C3, P4NP7S) type I, III and IV
      collagen in serum from 617 healthy men and women ranging in ages from 22 to 86.
      Subjects were divided into 5-year age groups according to their sex and age.
      Groups were compared using Kruskal-Wallis adjusted for Dunn's multiple
      comparisons test and Mann-Whitney t-test. Age-specific changes in collagen
      turnover was most profound for type I collagen. PINP levels decreased in men with
      advancing age, whereas in women, the level decreased in early adulthood followed
      by an increase around the age of menopause (age 40-60). Sex-specific changes in
      type I, III and IV collagen turnover was present at the age around menopause (age
      40-60) with women having an increased turnover. In summary, collagen turnover is
      affected by age and sex with the interstitial matrix and the basement membrane
      being differently regulated. The observed changes needs to be accounted for when
      measuring ECM related biomarkers in clinical studies.

PMID- 29596430
TI  - Integrating data from multiple sources for insights into demographic processes:
      Simulation studies and proof of concept for hierarchical change-in-ratio models.
AB  - We developed a model for estimating demographic rates and population abundance
      based on multiple data sets revealing information about population age- and sex
      structure. Such models have previously been described in the literature as change
      in-ratio models, but we extend the applicability of the models by i) using time
      series data allowing the full temporal dynamics to be modelled, by ii) casting
      the model in an explicit hierarchical modelling framework, and by iii) estimating
      parameters based on Bayesian inference. Based on sensitivity analyses we conclude
      that the approach developed here is able to obtain estimates of demographic rate
      with high precision whenever unbiased data of population structure are available.
      Our simulations revealed that this was true also when data on population
      abundance are not available or not included in the modelling framework.
      Nevertheless, when data on population structure are biased due to different
      observability of different age- and sex categories this will affect estimates of
      all demographic rates. Estimates of population size is particularly sensitive to
      such biases, whereas demographic rates can be relatively precisely estimated even
      with biased observation data as long as the bias is not severe. We then use the
      models to estimate demographic rates and population abundance for two Norwegian
      reindeer (Rangifer tarandus) populations where age-sex data were available for
      all harvested animals, and where population structure surveys were carried out in
      early summer (after calving) and late fall (after hunting season), and population
      size is counted in winter. We found that demographic rates were similar
      regardless whether we include population count data in the modelling, but that
      the estimated population size is affected by this decision. This suggest that
      monitoring programs that focus on population age- and sex structure will benefit
      from collecting additional data that allow estimation of observability for
      different age- and sex classes. In addition, our sensitivity analysis suggests
      that focusing monitoring towards changes in demographic rates might be more
      feasible than monitoring abundance in many situations where data on population
      age- and sex structure can be collected.

PMID- 29596431
TI  - Measuring the preparedness of health facilities to deliver emergency obstetric
      care in a South African district.
AB  - BACKGROUND: Improving the delivery of emergency obstetric care (EmNOC) remains
      critical in addressing direct causes of maternal mortality. United Nations (UN)
      agencies have promoted standard methods for evaluating the availability of EmNOC
      facilities although modifications have been proposed by others. This study
      presents an assessment of the preparedness of public health facilities to provide
      EmNOC using these methods in one South African district with a persistently high
      maternal mortality ratio. METHODS: Data collection took place in the final
      quarter of 2014. Cross-sectional surveys were conducted to classify the 7
      hospitals and 8 community health centres (CHCs) in the district as either basic
      EmNOC (BEmNOC) or comprehensive EmNOC (CEmNOC) facilities using UN EmNOC signal
      functions. The required density of EmNOC facilities was calculated using UN
      norms. We also assessed the availability of EmNOC personnel, resuscitation
      equipment, drugs, fluids, and protocols at each facility. The workload of skilled
      EmNOC providers at hospitals and CHCs was compared. RESULTS: All 7 hospitals in
      the district were classified as CEmNOC facilities, but none of the 8 CHCs
      performed all required signal functions to be classified as BEmNOC facilities. UN
      norms indicated that 25 EmNOC facilities were required for the district
      population, 5 of which should be CEmNOCs. None of the facilities had 100% of
      items on the EmNOC checklists. Hospital midwives delivered an average of 36.4+/
      14.3 deliveries each per month compared to only 7.9+/-3.2 for CHC midwives
      (p<0.001). CONCLUSIONS: The analysis indicated a shortfall of EmNOC facilities in
      the district. Full EmNOC services were centralised to hospitals to assure patient
      safety even though national policy guidelines sanction more decentralisation to
      CHCs. Studies measuring EmNOC availability need to consider facility opening
      hours, capacity and staffing in addition to the demonstrated performance of
      signal functions.

PMID- 29596432
TI  - Bold personality makes domestic dogs entering a shelter less vulnerable to
      diseases.
AB  - It is widely recognised that for vertebrate species, personalities vary along an
      axis with extremes represented by 'proactive' and 'reactive' individuals. The aim
      of this study was to verify whether there is a relationship between personality
      and disease vulnerability in domestic dogs (Canis familiaris) exposed to an
      intensely stressful situation such as entering a shelter. Twenty-eight shelter
      dogs participated in the study. The ethogram consisted of approximately 100
      behavioural patterns. Behavioural observations of dogs in their new environment,
      a Novel Object and a T-maze test were used to evaluate the personality of the
      dogs captured as strays and entering the shelter. A blood sample from each dog
      was obtained at admission into the shelter and after a month to evaluate their
      immunological state. Based on PCA analyses of observational combined with
      experimental data, the dogs were ordered along the boldness-shyness axis, with
      the first being the boldest. Excluding one (the 6th), the first 10 dogs showed an
      improved health status: absence of disease symptoms during the 30 days of
      monitoring and improved immunological parameters; the opposite was found for shy
      dogs. The results of this research seem to confirm findings in other vertebrate
      species, i.e., bold and shy dog vulnerability to diseases might be different,
      especially when they must cope with a stressful and highly infectious environment
      such as a dog shelter.

PMID- 29596433
TI  - The benzodiazepine-like natural product tilivalline is produced by the
      entomopathogenic bacterium Xenorhabdus eapokensis.
AB  - The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human
      gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated
      hemorrhagic colitis. Here we show the identification of tilivalline and analogs
      thereof in the entomopathogenic bacterium Xenorhabdus eapokensis as well as the
      identification of its biosynthesis gene cluster encoding a bimodular non
      ribosomal peptide synthetase. Heterologous expression of both genes in E. coli
      resulted in the production of 1 and from mutasynthesis and precursor directed
      biosynthesis 11 new tilivalline analogs were identified in X. eapokensis. These
      results allowed the prediction of the tilivalline biosynthesis being similar to
      that in K. oxytoca.

PMID- 29596434
TI  - Community-based MDR-TB care project improves treatment initiation in patients
      diagnosed with MDR-TB in Myanmar.
AB  - BACKGROUND: The Union in collaboration with national TB programme (NTP) started
      the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper
      Myanmar to improve treatment initiation and treatment adherence. Patients with
      MDR-TB diagnosed/registered under NTP received support through the project staff,
      in addition to the routine domiciliary care provided by NTP staff. Each township
      had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4
      months) were provided to the patient as a pre-treatment support. OBJECTIVES: To
      assess whether CBMDR-TBC project's support improved treatment initiation.
      METHODS: In this cohort study (involving record review) of all diagnosed MDR-TB
      between January 2015 and June 2016 in project townships, CBMDR-TBC status was
      categorized as "receiving support" if date of project initiation in patient's
      township was before the date of diagnosis and "not receiving support", if
      otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done
      to identify predictors of treatment initiation. RESULTS: Of 456 patients, 57%
      initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and
      "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in
      20 (4%) patients due to missing diagnosis dates). Among those initiated on
      treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76)
      days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among
      patients "not receiving support". After adjusting other potential confounders
      (age, sex, region, HIV, past history of TB treatment), patients "receiving
      support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3,
      2.3)] when compared to patients "not receiving support". In addition, age 15-54
      years, previous history of TB and being HIV negative were independent predictors
      of treatment initiation. CONCLUSION: Receiving support under CBMDR-TBC project
      improved treatment initiation: it not only improved the proportion initiated but
      also reduced time to treatment initiation. We also recommend improved tracking of
      all diagnosed patients as early as possible.

PMID- 29596436
TI  - Differences between nitrogen-tolerant and nitrogen-susceptible sweetpotato
      cultivars in photosynthate distribution and transport under different nitrogen
      conditions.
AB  - To characterize the differences in photosynthate distribution and transport
      between nitrogen(N)-tolerant and N-susceptible sweetpotato cultivars under
      different N conditions, three N levels, including 0 (N0), 120 (N120), and 240 kg
      ha-1 (N240), were used in field experiments with the Jishu26 (J26) and Xushu32
      (X32) cultivars in 2015 and 2016. The results from both years revealed that high
      N application reduced the tuberous root yield, the tuber/vine rate of carbon-13
      (13C), and top-to-base (three equal segments of stem divided from the fifth
      opened leaf of the shoot tip to the main stem, defined as the top, middle, and
      base parts, respectively) gradients such as sucrose, ammonia N and potassium
      along the stem. 'J26' showed a higher yield than 'X32' under N0 but lower yield
      than 'X32' under N120 and N240. It also exhibited a higher 13C distribution to
      tuberous roots compared with that of 'X32' under N0, and the opposite trend was
      observed under N120 and N240. Under N0, 'J26' showed a steep top-to-base amino
      acid gradient and a significantly lower top-to-base sucrose increase along the
      stem in the late growth stage. Under N120 and N240, 'X32' exhibited a greater top
      to-base decrease in the ammonia N along the stem during the main growth stages, a
      steep top-to-base sucrose gradient along the stem in the early growth stage, and
      a lower top-to-base sucrose increase along the stem in the middle and late growth
      stages. The formation of a reasonable photosynthate distribution structure
      attributed to high yield was related to a desirable sucrose, ammonia N or K+
      gradient downward along the stem. These results might help provide farmers with
      sweetpotato cultivars using less or no N fertilizer in soils of different
      fertility and enhance the knowledge of yield-related physiology.

PMID- 29596435
TI  - Integrated analysis of tumor differentiation genes in pancreatic adenocarcinoma.
AB  - BACKGROUND: Tumor differentiation is an important process in the development of
      cancer. It is valuable to identify key differentiation related genes in the
      prognosis and therapy of pancreatic adenocarcinoma. METHODS: The mRNA expression
      data were downloaded from the Cancer Genome Atlas database. Then, differentially
      expressed tumor differentiation related genes were identified. Additionally, Gene
      Ontology functional categories and Kyoto Encyclopedia of Genes and Genomes
      biochemical pathway was used to explore the function. In addition, receiver
      operating characteristic and survival analysis were carried out to assess the
      diagnosis and prognosis value. Finally, the electronic validation of selected
      tumor differentiation related genes was performed. RESULTS: A total of 932 genes
      were identified. Among which, 8 genes including JUB, ERLIN1, HMGA2, FAM110B,
      EGFR, MCM2, TCTA and SSTR1 were differentially expressed in all different tumor
      differentiation grades. Functional analysis revealed those genes between highly
      differentiated and other differentiation were remarkably enriched in pancreatic
      adenocarcinoma and cell cycle pathway. Finally, ERLIN1, HMGA2, FAM110B, EGFR,
      MCM2, BCL2L1, E2F1 and RAC1 were associated with the survival time of pancreatic
      adenocarcinoma patient. Among these genes, JUB, ERLIN1, FAM110B, MCM2 and BCL2L1
      also had a diagnosis value for pancreatic adenocarcinoma. Additionally, the
      expression trend of JUB, HMGA2 and MCM2 was increased along with the tumor
      differentiation grades. And the expression trend of FAM110B was decreased along
      with the tumor differentiation grades. The electronic validation result was
      consistent with the bioinformatics analysis. CONCLUSIONS: 12 tumor
      differentiation related genes including JUB, ERLIN1, HMGA2, FAM110B, EGFR, MCM2,
      TCTA, SSTR1, BCL2L1, E2F1, RAC1 and STAT1 played crucial roles in the
      differentiation of pancreatic adenocarcinoma.

PMID- 29596437
TI  - Are the unken reflex and the aposematic colouration of Red-Bellied Toads
      efficient against bird predation?
AB  - Aposematic signals as well as body behaviours may be important anti-predator
      defences. Species of the genus Melanophryniscus are characterised by having toxic
      lipophilic alkaloids in the skin and for presenting a red ventral colouration,
      which can be observed when they perform the behaviour called the unken reflex.
      Both the reflex behaviour and the colouration pattern are described as defence
      mechanisms. However, there are currently no studies testing their effectiveness
      against predators. This study aimed to test experimentally if both ventral
      conspicuous colouration and the unken reflex in Melanophryniscus cambaraensis
      function as aposematic signals against visually oriented predators (birds). We
      simulated the species studied using three different clay toad models as follows:
      (a) in a normal position with green coloured bodies, (b) in the unken reflex
      position with green coloured body and extremities and (c) in the unken reflex
      position with a green body and red extremities. Models were distributed on a
      known M. cambaraensis breeding site and in the adjacent forest. More than half of
      the attacks on the models were from birds; however, there was no preference for
      any model type. Thus, just the presence of the red colour associated with the
      motionless unken reflex position does not seem to prevent attacks from potential
      predators. It is possible that the effective aposematic signal in
      Melanophryniscus is achieved through the unken reflex movement together with the
      subsequent exhibition of the warning colouration and the secretion of toxins.

PMID- 29596438
TI  - Predation risk landscape modifies flying and red squirrel nest site occupancy
      independently of habitat amount.
AB  - Habitat choice often entails trade-offs between food availability and predation
      risk. Understanding the distribution of individuals in space thus requires that
      both habitat characteristics and predation risk are considered simultaneously.
      Here, we studied the nest box use of two arboreal squirrels who share preferred
      habitat with their main predators. Nocturnal Ural owls (Strix uralensis)
      decreased occurrence of night-active flying squirrels (Pteromys volans) and
      diurnal goshawks (Accipiter gentilis) that of day-active red squirrels (Sciurus
      vulgaris). Unexpectedly, the amount of preferred habitat had no effect on nest
      box use, but, surprisingly, both squirrel species seemed to benefit from close
      proximity to agricultural fields and red squirrels to urban areas. We found no
      evidence of trade-off between settling in a high-quality habitat and avoiding
      predators. However, the amount of poor-quality young pine forests was lower in
      occupied sites where goshawks were present, possibly indicating habitat specific
      predation on red squirrels. The results suggest that erecting nest boxes for Ural
      owls should be avoided in the vicinity of flying squirrel territories in order to
      conserve the near threatened flying squirrels. Our results also suggest that
      flying squirrels do not always need continuous old forests, and hence the
      currently insufficient conservation practices could be improved with reasonable
      increases in the areas left untouched around their nests. The results of this
      study demonstrate the importance of taking into account both habitat requirements
      and predation risk as well as their interactive effects when modeling the
      occupancy of threatened animal species and planning their conservation.

PMID- 29596439
TI  - Expression of progenitor markers is associated with the functionality of a
      bioartificial adrenal cortex.
AB  - Encapsulation of primary bovine adrenocortical cells in alginate is an
      efficacious model of a bioartificial adrenal cortex. Such a bioartificial adrenal
      cortex can be used for the restoration of lost adrenal function in vivo as well
      as for in vitro modeling of the adrenal microenvironment and for investigation of
      cell-cell interactions in the adrenals. The aim of this work was the optimization
      of a bioartificial adrenal cortex, that is the generation of a highly productive,
      self-regenerating, long-term functioning and immune tolerant bioartificial organ.
      To achieve this, it is necessary that adrenocortical stem and progenitor cells
      are present in the bioartificial gland, as these undifferentiated cells play
      important roles in the function of the mature gland. Here, we verified the
      presence of adrenocortical progenitors in cultures of bovine adrenocortical
      cells, studied the dynamics of their appearance and growth and determined the
      optimal time point for cell encapsulation. These procedures increased the
      functional life span and reduced the immunogenicity of the bioartificial adrenal
      cortex. This model allows the use of the luteinizing hormone-releasing hormone
      (LHRH) agonist triptorelin, the neuropeptide bombesin, and retinoic acid to alter
      cell number and the release of cortisol over long periods of time.

PMID- 29596441
TI  - Quantifying donor-to-donor variation in macrophage responses to the human fungal
      pathogen Cryptococcus neoformans.
AB  - Cryptococcosis remains the leading cause of fungal meningitis worldwide, caused
      primarily by the pathogen Cryptococcus neoformans. Symptomatic cryptococcal
      infections typically affect immunocompromised patients. However, environmental
      exposure to cryptococcal spores is ubiquitous and most healthy individuals are
      thought to harbor infections from early childhood onwards that are either
      resolved, or become latent. Since macrophages are a key host cell for
      cryptococcal infection, we sought to quantify the extent of individual variation
      in this early phagocyte response within a small cohort of healthy volunteers with
      no reported immunocompromising conditions. We show that rates of both
      intracellular fungal proliferation and non-lytic expulsion (vomocytosis) are
      remarkably variable between individuals. However, we demonstrate that neither
      gender, in vitro host inflammatory cytokine profiles, nor polymorphisms in
      several key immune genes are responsible for this variation. Thus the data we
      present serve to quantify the natural variation in macrophage responses to this
      important human pathogen and will hopefully provide a useful "benchmark" for the
      research community.

PMID- 29596440
TI  - Effectiveness of school food environment policies on children's dietary
      behaviors: A systematic review and meta-analysis.
AB  - BACKGROUND: School food environment policies may be a critical tool to promote
      healthy diets in children, yet their effectiveness remains unclear. OBJECTIVE: To
      systematically review and quantify the impact of school food environment policies
      on dietary habits, adiposity, and metabolic risk in children. METHODS: We
      systematically searched online databases for randomized or quasi-experimental
      interventions assessing effects of school food environment policies on children's
      dietary habits, adiposity, or metabolic risk factors. Data were extracted
      independently and in duplicate, and pooled using inverse-variance random-effects
      meta-analysis. Habitual (within+outside school) dietary intakes were the primary
      outcome. Heterogeneity was explored using meta-regression and subgroup analysis.
      Funnel plots, Begg's and Egger's test evaluated potential publication bias.
      RESULTS: From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in
      Europe/New Zealand) were included, on direct provision of healthful
      foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29),
      and school meal standards (N = 39) (some interventions assessed multiple
      policies). Direct provision policies, which largely targeted fruits and
      vegetables, increased consumption of fruits by 0.27 servings/d (n = 15 estimates
      (95%CI: 0.17, 0.36)) and combined fruits and vegetables by 0.28 servings/d (n =
      16 (0.17, 0.40)); with a slight impact on vegetables (n = 11; 0.04 (0.01, 0.08)),
      and no effects on total calories (n = 6; -56 kcal/d (-174, 62)). In interventions
      targeting water, habitual intake was unchanged (n = 3; 0.33 glasses/d (-0.27,
      0.93)). Competitive food/beverage standards reduced sugar-sweetened beverage
      intake by 0.18 servings/d (n = 3 (-0.31, -0.05)); and unhealthy snacks by 0.17
      servings/d (n = 2 (-0.22, -0.13)), without effects on total calories (n = 5; -79
      kcal/d (-179, 21)). School meal standards (mainly lunch) increased fruit intake
      (n = 2; 0.76 servings/d (0.37, 1.16)) and reduced total fat (-1.49%energy; n = 6
      (-2.42, -0.57)), saturated fat (n = 4; -0.93%energy (-1.15, -0.70)) and sodium (n
      = 4; -170 mg/d (-242, -98)); but not total calories (n = 8; -38 kcal/d (-137,
      62)). In 17 studies evaluating adiposity, significant decreases were generally
      not identified; few studies assessed metabolic factors (blood
      lipids/glucose/pressure), with mixed findings. Significant sources of
      heterogeneity or publication bias were not identified. CONCLUSIONS: Specific
      school food environment policies can improve targeted dietary behaviors; effects
      on adiposity and metabolic risk require further investigation. These findings
      inform ongoing policy discussions and debates on best practices to improve
      childhood dietary habits and health.

PMID- 29596442
TI  - Association of adverse childhood experiences and health risk behaviors among
      young adults visiting a regional primary healthcare center, Federation of Bosnia
      and Herzegovina.
AB  - BACKGROUND: Many studies have linked adverse childhood experiences (ACEs) to long
      term health outcomes, as well as health risk behaviors. In the post-war period in
      Bosnia and Herzegovina, many young people grew up in an environment of
      deteriorated living standards due to high unemployment and economic insecurity.
      The objectives of the study were to: 1) describe the health risk behaviors of
      young adults accessing primary healthcare; and 2) examine associations of these
      risk factors with adverse childhood experiences in this context. METHODS: This
      was a cross-sectional survey, conducted from April to October 2014. Participants
      were recruited from the Primary Healthcare Center Zenica. Patients between the
      ages of 18 and 24 were eligible for inclusion. The informed consent and self
      administered questionnaire were offered to patients during clinic intake. The
      questionnaire contained questions on sexual and reproductive health, use of
      alcohol and drugs, dating violence, and adverse childhood experiences. RESULTS:
      During the study period 520 questionnaires were distributed, and 400 complete
      surveys were returned, for a response rate of 76.9%. Among the 400 respondents,
      166 were males (41.5%) and 234 were females (58.5%). Our study showed that 48.7%
      of respondents had experienced some form of childhood adversity. Emotional
      neglect was the most common type of adverse childhood experience (25.6%) and was
      significantly more prevalent among females. Our study indicated that more than
      15% of respondents had witnessed domestic violence. Overall, ACEs were associated
      with increased odds of early sex initiation, alcohol use, drug use, and dating
      violence, although some of these associations did not reach statistical
      significance. Emotional neglect was the exception, and reporting emotional
      neglect was associated with a significantly elevated odds ratio for all four of
      the health risk behaviors. Emotional abuse was associated with an increased odds
      of drug abuse (OR = 2.78; 95% CI = 1.31-5.90) and dating violence (OR = 2.31; 95%
      CI = 1.10-4.89). Sexual abuse was marginally associated with increased early sex
      initiation (OR = 3.2; 95% CI 0.93-10.8). Parental divorce was significantly
      associated with alcohol abuse. CONCLUSION: The results of this study demonstrated
      associations between adverse experiences in childhood and the probability of
      engaging in health risk behavior which has implications for health outcomes in
      the long-term.

PMID- 29596443
TI  - Serum anti-glycan-antibodies in relatives of patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Serum anti-glycan antibodies are a promising tool for differential
      diagnosis, disease stratification and prediction of Crohn's disease (CD). To
      investigate possible heritability of the markers we assessed the presence of
      serum anti-glycan antibodies in affected and unaffected relatives of patients
      with CD. METHODS: Serum samples of 169 IBD patients of the German inflammatory
      bowel disease (IBD) network (140 CD & 29 Ulcerative colitis (UC)), 349 relatives
      of CD patients, 63 relatives of UC patients and 46 healthy controls were tested
      for the presence of anti-glycan antibodies by ELISA in a blinded fashion.
      Clinical data of the IBD patients and controls were available. RESULTS: A higher
      proportion of non-affected CD relatives was positive for anti-glycan antibodies
      compared to healthy subjects. No inheritance of a specific pattern of anti-glycan
      antibodies could be detected. No difference in marker expression depending on the
      degree of relationship in the non-affected relatives was noted and the presence
      of family history did not lead to a difference in marker levels in the affected
      CD subjects. CONCLUSIONS: Non-affected CD relatives had a higher frequency of
      anti-glycan antibodies compared to healthy subjects. This difference was mild and
      was found to be true for the overall reactivity to glycan antigens, but not for
      specific patterns. This may indicate an inherited mechanism resulting in a non
      specific increased reactivity to microbial antigens in IBD.

PMID- 29596444
TI  - Incidence and case fatality rates of community-acquired pneumonia and
      pneumococcal diseases among Korean adults: Catchment population-based analysis.
AB  - BACKGROUND: Pneumonia is a leading infectious cause of morbidity and mortality
      among adults. Pneumococcal pneumonia (PP) is the most common vaccine-preventable
      bacterial etiology of pneumonia. In this study, we estimated the incidence of
      community-acquired pneumonia (CAP) and pneumococcal diseases among Korean adults.
      METHODS: Clinical and microbiological databases from three hospitals were
      retrospectively reviewed to determine the incidence and case fatality rates of
      CAP and pneumococcal diseases in Korean adults aged >=19 years from 2011 to 2014.
      Incidence and case fatality rates of CAP, PP and invasive pneumococcal diseases
      (IPD) were evaluated based on the catchment population. Catchment population was
      calculated using national health insurance data, estimating the proportion of
      patients with pneumonia that were medically attended at each hospital. RESULTS:
      Among 5,783 patients with medically attended CAP, 833 (14.4%) had PP. For IPD, a
      total of 91 culture-confirmed cases were identified. The overall incidence of CAP
      was 307.7 cases per 100,000 persons per year with an in-hospital mortality rate
      of 6.2%. The estimated annual incidence of pneumococcal pneumonia was 42.2-49.4
      cases per 100,000 persons per year, increasing with age to >280 per 100,000
      persons per year in older patients over 70 years. The annual incidence of IPD had
      a range of 4.1-6.5 cases per 100,000 persons per year. The overall case fatality
      rate for invasive pneumococcal diseases was 30.8% with the highest rate of 66.7%
      in patients over 80 years. CONCLUSION: Over the study period, incidences of CAP,
      PP and IPD were consistently high, particularly in older people. These results
      provide baseline data to establish healthcare strategies and estimate their
      impact among Korean adults.

PMID- 29596445
TI  - Time spent with cats is never wasted: Lessons learned from feline acromegalic
      cardiomyopathy, a naturally occurring animal model of the human disease.
AB  - BACKGROUND: In humans, acromegaly due to a pituitary somatotrophic adenoma is a
      recognized cause of increased left ventricular (LV) mass. Acromegalic
      cardiomyopathy is incompletely understood, and represents a major cause of
      morbidity and mortality. We describe the clinical, echocardiographic and
      histopathologic features of naturally occurring feline acromegalic
      cardiomyopathy, an emerging disease among domestic cats. METHODS: Cats with
      confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were
      prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n
      = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n
      = 16). Echocardiography was performed in all cases, including after
      hypersomatotropism treatment where applicable. Additionally, tissue samples from
      deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age
      matched controls (n = 21 each) were collected and systematically
      histopathologically reviewed and compared. RESULTS: By echocardiography, cats
      with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1
      10.1mm) than diabetic (5.9mm, 4.2-9.1mm; Mann Whitney, p<0.001) or control cats
      (5.2mm, 4.1-6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater
      in cats with hypersomatotropism (16.6mm, 13.0-29.5mm) than in diabetic (15.4mm,
      11.2-20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6-17.4mm; Mann
      Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration
      (n = 20), echocardiographic changes proved mostly reversible. As in humans,
      histopathology of the feline acromegalic heart was dominated by myocyte
      hypertrophy with interstitial fibrosis and minimal myofiber disarray.
      CONCLUSIONS: These results demonstrate cats could be considered a naturally
      occurring model of acromegalic cardiomyopathy, and as such help elucidate
      mechanisms driving cardiovascular remodeling in this disease.

PMID- 29596446
TI  - Gut microbiota varies by opioid use, circulating leptin and oxytocin in African
      American men with diabetes and high burden of chronic disease.
AB  - OBJECTIVE: The gut microbiota is known to be related to type 2 diabetes (T2D),
      psychiatric conditions, and opioid use. In this study, we tested the hypothesis
      that variability in gut microbiota in T2D is associated with psycho-metabolic
      health. METHODS: A cross-sectional study was conducted among African American men
      (AAM) (n = 99) that were outpatients at a Chicago VA Medical Center. The main
      outcome measures included fecal microbiota ecology (by 16S rRNA gene sequencing),
      psychiatric disorders including opioid use, and circulating leptin and oxytocin
      as representative hormone biomarkers for obesity and psychological pro-social
      behavior. RESULTS: The study subjects had prevalent overweight/obesity (78%), T2D
      (50%) and co-morbid psychiatric (65%) and opioid use (45%) disorders. In the
      analysis of microbiota, the data showed interactions of opioids, T2D and
      metformin with Bifidobacterium and Prevotella genera. The differential analysis
      of Bifidobacterium stratified by opioids, T2D and metformin, showed significant
      interactions among these factors indicating that the effect of one factor was
      changed by the other (FDR-adjusted p [q] < 0.01). In addition, the pair-wise
      comparison showed that participants with T2D not taking metformin had a
      significant 6.74 log2 fold increase in Bifidobacterium in opioid users as
      compared to non-users (q = 2.2 x 10-8). Since metformin was not included in this
      pair-wise comparison, the significant 'q' suggested association of opioid use
      with Bifidobacterium abundance. The differences in Bifidobacterium abundance
      could possibly be explained by opioids acting as organic cation transporter 1
      (OCT1) inhibitors. Analysis stratified by lower and higher leptin and oxytocin
      (divided by the 50th percentile) in the subgroup without T2D showed lower
      Dialister in High-Leptin vs. Low-Leptin (p = 0.03). Contrary, the opposite was
      shown for oxytocin, higher Dialister in High-Oxytocin vs. Low-Oxytocin (p =
      0.04). CONCLUSIONS: The study demonstrated for the first time that
      Bifidobacterium and Prevotella abundance was affected by interactions of T2D,
      metformin and opioid use. Also, in subjects without T2D Dialister abundance
      varied according to circulating leptin and oxytocin.

PMID- 29596448
TI  - Solution of magnetohydrodynamic flow and heat transfer of radiative viscoelastic
      fluid with temperature dependent viscosity in wire coating analysis.
AB  - Wire coating process is a continuous extrusion process for primary insulation of
      conducting wires with molten polymers for mechanical strength and protection in
      aggressive environments. In the present study, radiative melt polymer satisfying
      third grade fluid model is used for wire coating process. The effect of magnetic
      parameter, thermal radiation parameter and temperature dependent viscosity on
      wire coating analysis has been investigated. Reynolds model and Vogel's models
      have been incorporated for variable viscosity. The governing equations
      characterizing the flow and heat transfer phenomena are solved analytically by
      utilizing homotopy analysis method (HAM). The computed results are also verified
      by ND-Solve method (Numerical technique) and Adomian Decomposition Method (ADM).
      The effect of pertinent parameters is shown graphically. In addition, the
      instability of the flow in the flows of the wall of the extrusion die is well
      marked in the case of the Vogel model as pointed by Nhan-Phan-Thien.

PMID- 29596447
TI  - Citrus aurantium L. dry extracts promote C/ebpbeta expression and improve
      adipocyte differentiation in 3T3-L1 cells.
AB  - Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT)
      contribute to the development of metabolic disorders, such as Type 2 Diabetes
      (T2D). Therefore, the identification of products able to improve adipose tissue
      function represents a valuable strategy for the prevention and/or treatment of
      T2D. In the current study, we investigated the potential effects of dry extracts
      obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1
      cells adipocyte differentiation and function in vitro. We found that CAde
      enhances terminal adipocyte differentiation of 3T3-L1 cells raising the
      expression of CCAAT/enhancer binding protein beta (C/Ebpbeta), peroxisome
      proliferator activated receptor gamma (Ppargamma), glucose transporter type 4
      (Glut4) and fatty acid binding protein 4 (Fabp4). CAde improves insulin-induced
      glucose uptake of 3T3-L1 adipocytes, as well. A focused analysis of the phases
      occurring in the pre-adipocytes differentiation to mature adipocytes furthermore
      revealed that CAde promotes the early differentiation stage by up-regulating
      C/ebpbeta expression at 2, 4 and 8 h post the adipogenic induction and
      anticipating the 3T3-L1 cell cycle entry and progression during mitotic clonal
      expansion (MCE). These findings provide evidence that the exposure to CAde
      enhances in vitro fat cell differentiation of pre-adipocytes and functional
      capacity of mature adipocytes, and pave the way to the development of products
      derived from Citrus aurantium L. fruit juice, which may improve WAT functional
      capacity and may be effective for the prevention and/or treatment of T2D.

PMID- 29596449
TI  - Sequence analysis of the potato aphid Macrosiphum euphorbiae transcriptome
      identified two new viruses.
AB  - The potato aphid, Macrosiphum euphorbiae, is an important agricultural pest that
      causes economic losses to potato and tomato production. To establish the
      transcriptome for this aphid, RNA-Seq libraries constructed from aphids
      maintained on tomato plants were used in Illumina sequencing generating 52.6
      million 75-105 bp paired-end reads. The reads were assembled using Velvet/Oases
      software with SEED preprocessing resulting in 22,137 contigs with an N50 value of
      2,003bp. After removal of contigs from tomato host origin, 20,254 contigs were
      annotated using BLASTx searches against the non-redundant protein database from
      the National Center for Biotechnology Information (NCBI) as well as
      IntereProScan. This identified matches for 74% of the potato aphid contigs. The
      highest ranking hits for over 12,700 contigs were against the related pea aphid,
      Acyrthosiphon pisum. Gene Ontology (GO) was used to classify the identified M.
      euphorbiae contigs into biological process, cellular component and molecular
      function. Among the contigs, sequences of microbial origin were identified. Sixty
      five contigs were from the aphid bacterial obligate endosymbiont Buchnera
      aphidicola origin and two contigs had amino acid similarities to viruses. The
      latter two were named Macrosiphum euphorbiae virus 2 (MeV-2) and Macrosiphum
      euphorbiae virus 3 (MeV-3). The highest sequence identity to MeV-2 had the
      Dysaphis plantaginea densovirus, while to MeV-3 is the Hubei sobemo-like virus
      49. Characterization of MeV-2 and MeV-3 indicated that both are transmitted
      vertically from adult aphids to nymphs. MeV-2 peptides were detected in the aphid
      saliva and only MeV-2 and not MeV-3 nucleic acids were detected inside tomato
      leaves exposed to virus-infected aphids. However, MeV-2 nucleic acids did not
      persist in tomato leaf tissues, after clearing the plants from aphids, indicating
      that MeV-2 is likely an aphid virus.

PMID- 29596450
TI  - Manual muscle testing and hand-held dynamometry in people with inflammatory
      myopathy: An intra- and interrater reliability and validity study.
AB  - Manual muscle testing (MMT) and hand-held dynamometry (HHD) are commonly used in
      people with inflammatory myopathy (IM), but their clinimetric properties have not
      yet been sufficiently studied. To evaluate the reliability and validity of MMT
      and HHD, maximum isometric strength was measured in eight muscle groups across
      three measurement events. To evaluate reliability of HHD, intra-class correlation
      coefficients (ICC), the standard error of measurements (SEM) and smallest
      detectable changes (SDC) were calculated. To measure reliability of MMT linear
      Cohen's Kappa was computed for single muscle groups and ICC for total score.
      Additionally, correlations between MMT8 and HHD were evaluated with Spearman
      Correlation Coefficients. Fifty people with myositis (56+/-14 years, 76% female)
      were included in the study. Intra-and interrater reliability of HHD yielded
      excellent ICCs (0.75-0.97) for all muscle groups, except for interrater
      reliability of ankle extension (0.61). The corresponding SEMs% ranged from 8 to
      28% and the SDCs% from 23 to 65%. MMT8 total score revealed excellent intra-and
      interrater reliability (ICC>0.9). Intrarater reliability of single muscle groups
      was substantial for shoulder and hip abduction, elbow and neck flexion, and hip
      extension (0.64-0.69); moderate for wrist (0.53) and knee extension (0.49) and
      fair for ankle extension (0.35). Interrater reliability was moderate for neck
      flexion (0.54) and hip abduction (0.44); fair for shoulder abduction, elbow
      flexion, wrist and ankle extension (0.20-0.33); and slight for knee extension
      (0.08). Correlations between the two tests were low for wrist, knee, ankle, and
      hip extension; moderate for elbow flexion, neck flexion and hip abduction; and
      good for shoulder abduction. In conclusion, the MMT8 total score is a reliable
      assessment to consider general muscle weakness in people with myositis but not
      for single muscle groups. In contrast, our results confirm that HHD can be
      recommended to evaluate strength of single muscle groups.

PMID- 29596451
TI  - Exogenous application of the plant signalers methyl jasmonate and salicylic acid
      induces changes in volatile emissions from citrus foliage and influences the
      aggregation behavior of Asian citrus psyllid (Diaphorina citri), vector of
      Huanglongbing.
AB  - Huanglongbing, also known as citrus greening, is a destructive disease that
      threatens citrus production worldwide. It is putatively caused by the phloem
      limited bacterium Candidatus Liberibacter asiaticus (Las). Currently, the disease
      is untreatable and efforts focus on intensive insecticide use to control the
      vector, Asian citrus psyllid (Diaphorina citri). Emerging psyllid resistance to
      multiple insecticides has generated investigations into the use of exogenously
      applied signaling compounds to enhance citrus resistance to D. citri and Las. In
      the present study, we examined whether foliar applications of methyl jasmonate
      (MJ), a volatile signaling compound associated with the induced systemic
      resistance pathway, and salicylic acid, a constituent of the systemic acquired
      resistance pathway, would elicit the emission of defense-related volatiles in
      citrus foliage, and what effect this might have on the host-plant searching
      behavior of D. citri. Comparisons were made of volatiles emitted from growing
      shoots of uninfected and Las-infected 'Valencia' sweet orange (Citrus sinensis)
      trees over two consecutive sampling days. A settling behavioral assay was used to
      compare psyllid attraction to MJ-treated vs. Tween-treated citrus sprigs. All
      three main effects, Las infection status, plant signaler application, and
      sampling day, influenced the proportions of individual volatile compounds emitted
      in different treatment groups. MJ- and SA-treated trees had higher emission rates
      than Tween-treated trees. Methyl salicylate (MeSA) and beta-caryophyllene were
      present in higher proportions in the volatiles collected from Las-infected +
      trees. On the other hand, Las-infected + MJ-treated trees emitted lower
      proportions of MeSA than did Las-infected + Tween-treated trees. Because MeSA is
      a key D. citri attractant, this result suggests that MJ application could
      suppress MeSA emission from Las-infected trees, an approach that could be used to
      discourage psyllid colonization during shoot growth. MJ application enhanced
      emission of E-beta-ocimene, indole, volatiles attractive to many of the psyllid's
      natural enemies, indicating that MJ application could be used in an 'attract and
      reward' conservation biological control strategy. Volatile emissions in SA
      treated trees were dominated by MeSA. MJ application elicited aggregation
      behavior in D. citri. Similar numbers of psyllids settled on MJ-treated versus
      Tween-treated sprigs, but a significantly greater percentage of the MJ-treated
      sprigs had aggregations of nine or more psyllids on them. Taken together, the
      results of this study indicate that exogenous applications of MJ or SA could be
      used to influence Asian citrus psyllid settling behavior and attract its natural
      enemies.

PMID- 29596452
TI  - Anaerobic metabolism induces greater total energy expenditure during exercise
      with blood flow restriction.
AB  - PURPOSE: We investigated the energy system contributions and total energy
      expenditure during low intensity endurance exercise associated with blood flow
      restriction (LIE-BFR) and without blood flow restriction (LIE). METHODS: Twelve
      males participated in a contra-balanced, cross-over design in which subjects
      completed a bout of low-intensity endurance exercise (30min cycling at 40% of
      [Formula: see text]) with or without BFR, separated by at least 72 hours of
      recovery. Blood lactate accumulation and oxygen uptake during and after exercise
      were used to estimate the anaerobic lactic metabolism, aerobic metabolism, and
      anaerobic alactic metabolism contributions, respectively. RESULTS: There were
      significant increases in the anaerobic lactic metabolism (P = 0.008), aerobic
      metabolism (P = 0.020), and total energy expenditure (P = 0.008) in the LIE-BFR.
      No significant differences between conditions for the anaerobic alactic
      metabolism were found (P = 0.582). Plasma lactate concentration was significantly
      higher in the LIE-BFR at 15min and peak post-exercise (all P<=0.008). Heart rate
      was significantly higher in the LIE-BFR at 10, 15, 20, 25, and 30min during
      exercise, and 5, 10, and 15min after exercise (all P<=0.03). Ventilation was
      significantly higher in the LIE-BFR at 10, 15, and 20min during exercise (all
      P<=0.003). CONCLUSION: Low-intensity endurance exercise performed with blood flow
      restriction increases the anaerobic lactic and aerobic metabolisms, total energy
      expenditure, and cardiorespiratory responses.

PMID- 29596453
TI  - Sponges-Cyanobacteria associations: Global diversity overview and new data from
      the Eastern Mediterranean.
AB  - Sponge-cyanobacteria associations have attracted research interest from an
      ecological, evolutionary and biotechnological perspective. Current knowledge is,
      in its majority, "hidden" in metagenomics research studying the entire microbial
      communities of sponges, while knowledge on these associations is totally missing
      for certain geographic areas. In this study, we (a) investigated the occurrence
      of cyanobacteria in 18 sponge species, several of which are studied for the first
      time for their cyanobionts, from a previously unexplored eastern Mediterranean
      ecoregion, the Aegean Sea, (b) isolated sponge-associated cyanobacteria, and
      characterized them based on a polyphasic (morphological-morphometric and
      molecular phylogenetic analysis) approach, and (c) conducted a meta-analysis on
      the global diversity of sponge species hosting cyanobacteria, as well as the
      diversity of cyanobacterial symbionts. Our research provided new records for nine
      sponge species, previously unknown for this association, while the isolated
      cyanobacteria were found to form novel clades within Synechococcus,
      Leptolyngbyaceae, Pseudanabaenaceae, and Schizotrichaceae, whose taxonomic status
      requires further investigation; this is the first report of a Schizotrichaceae
      cyanobacterium associated with sponges. The extensive evaluation of the
      literature along with the new data from the Aegean Sea raised the number of
      sponge species known for hosting cyanobacteria to 320 and showed that the
      cyanobacterial diversity reported from sponges is yet underestimated.

PMID- 29596454
TI  - Classification of atrophic mucosal patterns on Blue LASER Imaging for endoscopic
      diagnosis of Helicobacter pylori-related gastritis: A retrospective,
      observational study.
AB  - BACKGROUND: Atrophic gastritis can be classified according to characteristic
      mucosal patterns observed by Blue LASER Imaging (BLI) in a medium-range to
      distant view. AIMS: To facilitate the endoscopic diagnosis of Helicobacter pylori
      (HP)-related gastritis, we investigated whether atrophic mucosal patterns
      correlated with HP infection based on the image interpretations of three
      endoscopists blinded to clinical features. METHODS: This study included 441
      patients diagnosed as having atrophic gastritis by upper gastrointestinal
      endoscopy at Nishikawa Gastrointestinal Clinic between April 1, 2015 and March
      31, 2016. The presence/absence of HP infection was not taken into consideration.
      Endoscopy was performed using a Fujifilm EG-L580NW scope. Atrophic mucosal
      patterns observed by BLI were classified into Spotty, Cracked and Mottled. Image
      interpretation results were that 89, 122 and 228 patients had the Spotty, Cracked
      and Mottled patterns, respectively, and 2 patients an undetermined pattern.
      Further analyses were performed on 439 patients, excluding the 2 with
      undetermined patterns. RESULTS: The numbers of patients testing negative/positive
      for HP infection in the Spotty, Cracked and Mottled pattern groups were 12/77,
      105/17, and 138/90, respectively. The specificity, positive predictive value and
      positive likelihood ratio for endoscopic diagnosis with positive HP infection
      based on the Spotty pattern were 95.3%, 86.5% and 8.9, respectively. In all
      patients with the Spotty pattern before HP eradication, the Cracked pattern was
      observed on subsequent post-eradication endoscopy. CONCLUSIONS: The Spotty
      pattern may represent the presence of HP infection, the Cracked pattern, a post
      inflammatory change as seen after HP eradication, and the Mottled pattern,
      intestinal metaplasia.

PMID- 29596455
TI  - Flip-flop method: A new T1-weighted flow-MRI for plants studies.
AB  - The climate warming implies an increase of stress of plants (drought and
      torrential rainfall). The understanding of plant behavior, in this context, takes
      a major importance and sap flow measurement in plants remains a key issue for
      plant understanding. Magnetic Resonance Imaging (MRI) which is well known to be a
      powerful tool to access water quantity can be used to measure moving water. We
      describe a novel flow-MRI method which takes advantage of inflow slice
      sensitivity. The method involves the slice selectivity in the context of multi
      slice spin echo sequence. Two sequences such as a given slice is consecutively
      inflow and outflow sensitive are performed, offering the possiblility to perform
      slow flow sensitive imaging in a quite straigthforward way. The method potential
      is demonstrated by imaging both a slow flow measurement on a test bench (as low
      as 10 MUm.s-1) and the Poiseuille's profile of xylemian sap flow velocity in the
      xylematic tissues of a tomato plant stem.

PMID- 29596456
TI  - Modelling southern elephant seals Mirounga leonina using an individual-based
      model coupled with a dynamic energy budget.
AB  - Higher trophic-level species are an integral component of any marine ecosystem.
      Despite their importance, methods for representing these species in end-to-end
      ecosystem models often have limited representation of life histories, energetics
      and behaviour. We built an individual-based model coupled with a dynamic energy
      budget for female southern elephant seals Mirounga leonina to demonstrate a
      method for detailed representation of marine mammals. We aimed to develop a model
      which could i) simulate energy use and life histories, as well as breeding traits
      of southern elephant seals in an emergent manner, ii) project a stable population
      over time, and iii) have realistic population dynamics and structure based on
      emergent life history features (such as age at first breeding, lifespan,
      fecundity and (yearling) survival). We evaluated the model's ability to represent
      a stable population over long time periods (>10 generations), including the
      sensitivity of the emergent properties to variations in key parameters. Analyses
      indicated that the model is sensitive to changes in resource availability and
      energy requirements for the transition from pup to juvenile, and juvenile to
      adult stage. This was particularly the case for breeding success and yearling
      survival. This model is suitable for use as a standalone tool for investigating
      the impacts of changes to behaviour and population responses of southern elephant
      seals.

PMID- 29596457
TI  - Effects of functionalized multi-walled carbon nanotubes on toxicity and
      bioaccumulation of lead in Daphnia magna.
AB  - Increased production of carbon nanotubes (CNTs) and their widespread application
      in industrial and consumer products have led to a rise in the release of CNTs
      into the aquatic environment. CNTs have a very strong adsorption affinity for
      various environmental contaminants; therefore, they may also influence the toxic
      effects of other pollutants, such as toxic metals. In this study, the effect of
      two different functionalized carbon nanotubes, carboxylate and polyethyleneimine
      modified multi-walled carbon nanotubes (C-MWCNTs and N-MWCNT, respectively) on
      lead toxicity and bioaccumulation was investigated with a freshwater zooplankton
      Daphnia magna. The acute toxicity results indicate that the different surface
      properties of the two types of MWCNTs have different effects on lead toxicity to
      D. magna. The negatively charged C-MWCNT showed a notable decrease in lead
      toxicity (LC50 value increased from 0.15 mg L-1 to 1.08 mg L-1 in the presence of
      10 mg L-1 C-MWCNT), whereas the positively charged N-MWCNT had only a slight
      effect on lead toxicity (LC50 value increased from 0.15 mg L-1 to 0.16 mg L-1 in
      the presence of 10 mg L-1 N-MWCNT). The decrease of lead toxicity was related
      with the reduced bioavailability of free metal form (Pb2+) caused by greater
      adsorption of lead onto the MWCNTs. The present study suggests that there is a
      need to consider carefully the complex interaction of CNTs with toxic metals in
      future ecotoxicological studies.

PMID- 29596458
TI  - Quantitative N-glycoproteomics reveals altered glycosylation levels of various
      plasma proteins in bloodstream infected patients.
AB  - Bloodstream infections are associated with high morbidity and mortality with
      rates varying from 10-25% and higher. Appropriate and timely onset of antibiotic
      therapy influences the prognosis of these patients. It requires the diagnostic
      accuracy which is not afforded by current gold standards such as blood culture.
      Moreover, the time from blood sampling to blood culture results is a key
      determinant of reducing mortality. No established biomarkers exist which can
      differentiate bloodstream infections from other systemic inflammatory conditions.
      This calls for studies on biomarkers potential of molecular profiling of plasma
      as it is affected most by the molecular changes accompanying bloodstream
      infections. N-glycosylation is a post-translational modification which is very
      sensitive to changes in physiology. Here we have performed targeted quantitative
      N-glycoproteomics from plasma samples of patients with confirmed positive blood
      culture together with age and sex matched febrile controls with negative blood
      culture reports. Three hundred and sixty eight potential N-glycopeptides were
      quantified by mass spectrometry and 149 were further selected for identification.
      Twenty four N-glycopeptides were identified with high confidence together with
      elucidation of the peptide sequence, N-glycosylation site, glycan composition and
      proposed glycan structures. Principal component analysis, orthogonal projections
      to latent structures-discriminant analysis (S-Plot) and self-organizing maps
      clustering among other statistical methods were employed to analyze the data.
      These methods gave us clear separation of the two patient classes. We propose
      high-confidence N-glycopeptides which have the power to separate the bloodstream
      infections from blood culture negative febrile patients and shed light on host
      response during bacteremia. Data are available via ProteomeXchange with
      identifier PXD009048.

PMID- 29596459
TI  - Clinicians' perspectives on incidentally discovered silent brain infarcts - A
      qualitative study.
AB  - BACKGROUND: While silent brain infarcts (SBIs) in screened cohorts are associated
      with risk of symptomatic stroke and dementia, the clinical significance of
      incidentally discovered SBIs (id-SBIs) is unknown. Detection may offer an
      opportunity to initiate prevention measures, but uncertainties about id-SBIs may
      impede clinicians from addressing them and complicate further study of this
      condition. METHODS AND RESULTS: This study used semi-structured interviews of
      practicing clinicians. Interviews were audio recorded, transcribed, and analyzed
      using a grounded theory approach. A constant comparative method was used to
      organize emergent themes and examine new themes. Purposeful sampling was employed
      to achieve participant diversity. Fifteen clinicians were interviewed. Emergent
      themes centered on uncertainty about id-SBIs, clinical decision making in
      response to uncertainty, and evidence needed to resolve uncertainty. All
      clinicians reported uncertainty about id-SBIs: diagnostic, prognostic, or
      therapeutic. Differential responses to uncertainties resulted in practice
      variation within and between specialties. Diagnostic and prognostic uncertainty
      discouraged disclosure of imaging findings to patients. Vascular neurologists
      viewed the prognostic significance of id-SBIs as similar to symptomatic stroke.
      Therapeutic uncertainty was common, but most participants endorsed using stroke
      secondary prevention strategies. Regarding future research, all internists
      indicated they would consider changing practices in response to observational
      studies, whereas half of the neurologists expressed reluctance to modify
      practices based on non-randomized data. Several expressed concerns about clinical
      trial feasibility and lack of equipoise. CONCLUSIONS: id-SBIs are a focus of
      uncertainty for clinicians, leading to practice variation. Future studies must
      address diagnostic and prognostic uncertainty to facilitate implementation of
      prevention strategies.

PMID- 29596460
TI  - Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review.
AB  - Type 1 diabetes is an autoimmune condition characterised by pancreatic beta cell
      destruction and absolute insulin deficiency. The strongest predictor of diabetes
      complications is glycaemic control and achieving HbA1c <= 7.0% is the primary
      management target. However, standard treatment appears to be lacking and
      adjunctive strategies require consideration. A systematic review was conducted to
      examine the effect of low-carbohydrate diets on type 1 diabetes management. Four
      databases were searched from inception until 28 March 2017: MEDLINE; CINAHL;
      Cochrane Library; and EMBASE. All primary studies containing a methods section
      (excluding cross-sectional) were included. Reports had to quantitatively measure
      the effect(s) of a dietary intervention or observed intake over at least two
      weeks where carbohydrate is below 45% total energy in adults and/or children with
      type 1 diabetes. The primary outcome was HbA1c and secondary outcomes were severe
      hypoglycaemia, total daily insulin, BMI, quality of life and mean daily glucose.
      Seventy-nine full-text articles were assessed for eligibility and nine were
      included (two randomised controlled trials, four pre-post interventions, two case
      series, one case-report). Eight studies reported a mean change in HbA1c with a
      low-carbohydrate diet. Of these, four reported a non-significant change (P >=
      0.05) and three reported statistically significant reductions (P < 0.05). Two
      studies reported severe hypoglycaemia, five reported total insulin, three
      reported BMI, and one reported blood glucose. Due to the significant
      heterogeneity of included studies, an overall effect could not be determined.
      This review presents all available evidence on low-carbohydrate diets for type 1
      diabetes and suggests an urgent need for more primary studies.

PMID- 29596461
TI  - CT utilization abruptly increases at age 18 among patients with inflammatory
      bowel diseases in the hospital.
AB  - OBJECTIVES: Patients with inflammatory bowel disease(IBD) are frequently exposed
      to computed tomography (CT). Each CT exposes patients to radiation that
      cumulatively could increase the risk of malignancy, particularly in younger
      patients. We aim to study the effect of age on CT use in IBD patients seen in the
      Emergency Department (ED) or the hospital. METHODS: We conducted a retrospective
      cohort study of IBD patients identified in Truven Health Marketscan databases
      between 2009-2013. The main outcome was use of CT during an ED or inpatient
      visit. Effect of age on CT use was characterized using logistic regression
      accounting for important covariables. RESULTS: There were 66,731 patients with
      IBD with 144,147 ED or inpatient visits in this cohort with a diagnosis code of
      IBD. At first visit, 5.8% percent were below age 18. CT was utilized in 26.6% of
      visits. In multivariable analysis, adjusting for medications, recent surgery, and
      gender, patients 18-35 were more likely to undergo CT (OR 2.35, 95%CI: 2.20-2.52)
      compared to those <18. Examining patients only between 16 and 19, the odds of an
      18 or 19-year-old undergoing CT is significantly higher than a 16 or 17-year-old
      (OR 1.96, 95%CI: 1.71-2.24). CONCLUSIONS: Patients with IBD undergo CT more than
      a quarter of the time in the ED or inpatient setting. Pediatric providers limit
      radiation exposure among those <18 while adult providers are not as cautious with
      radiation exposure for the young adult population. Increased awareness of the
      risks of cumulative radiation exposure in the young adult population is needed.

PMID- 29596462
TI  - Racial disparities in the prevalence and control of hypertension among a cohort
      of HIV-infected patients in the southeastern United States.
AB  - BACKGROUND: African Americans are disproportionately affected by both HIV and
      hypertension. Failure to modify risk factors for cardiovascular disease and
      chronic kidney disease such as hypertension among HIV-infected patients may
      attenuate the benefits conferred by combination antiretroviral therapy. In the
      general population, African Americans with hypertension are less likely to have
      controlled blood pressure than whites. However, racial differences in blood
      pressure control among HIV-infected patients are not well studied. METHODS: We
      conducted a cross-sectional study evaluating racial differences in hypertension
      prevalence, treatment, and control among 1,664 patients attending the University
      of Alabama at Birmingham HIV Clinic in 2013. Multivariable analyses were
      performed to calculate prevalence ratios (PR) with 95% confidence intervals (CI)
      as the measure of association between race and hypertension prevalence and
      control while adjusting for other covariates. RESULTS: The mean age of patients
      was 47 years, 77% were male and 54% African-American. The prevalence of
      hypertension was higher among African Americans compared with whites (49% vs.
      43%; p = 0.02). Among those with hypertension, 91% of African Americans and 93%
      of whites were treated (p = 0.43). Among those treated, 50% of African Americans
      versus 60% of whites had controlled blood pressure (systolic blood pressure <140
      mmHg and diastolic blood pressure <90 mmHg) (p = 0.007). After multivariable
      adjustment for potential confounders, prevalence of hypertension was higher among
      African Americans compared to whites (PR 1.25; 95% CI 1.12-1.39) and prevalence
      of BP control was lower (PR 0.80; 95% CI 0.69-0.93). CONCLUSIONS: Despite
      comparable levels of hypertension treatment, African Americans in our HIV cohort
      were less likely to achieve blood pressure control. This may place them at
      increased risk for adverse outcomes that disproportionately impact HIV-infected
      patients, such as cardiovascular disease and chronic kidney disease, and thus
      attenuate the benefits conferred by combination antiretroviral therapy.

PMID- 29596463
TI  - Inhibin betaE (INHBE) is a possible insulin resistance-associated hepatokine
      identified by comprehensive gene expression analysis in human liver biopsy
      samples.
AB  - The liver plays a major role in whole-body energy homeostasis by releasing
      secretory factors, termed hepatokines. To identify novel target genes associated
      with insulin resistance, we performed a comprehensive analysis of gene expression
      profiles using a DNA chip method in liver biopsy samples from humans with varying
      degrees of insulin resistance. Inhibin betaE (INHBE) was identified as a novel
      putative hepatokine with hepatic gene expression that positively correlated with
      insulin resistance and body mass index in humans. Quantitative real time-PCR
      analysis also showed an increase in INHBE gene expression in independent liver
      samples from insulin-resistant human subjects. Additionally, Inhbe gene
      expression increased in the livers of db/db mice, a rodent model of type 2
      diabetes. To preliminarily screen the role of Inhbe in vivo in whole-body energy
      metabolic status, hepatic mRNA was knocked down with siRNA for Inhbe (siINHBE) in
      db/db mice. Treatment with siINHBE suppressed body weight gain during the two
      week experimental period, which was attributable to diminished fat rather than
      lean mass. Additionally, treatment with siINHBE decreased the respiratory
      quotient and increased plasma total ketone bodies compared with treatment with
      non-targeting siRNA, both of which suggest enhanced whole-body fat utilization.
      Our study suggests that INHBE functions as a possible hepatokine to alter the
      whole-body metabolic status under obese insulin-resistant conditions.

PMID- 29596464
TI  - Potential geographic "hotspots" for drug-injection related transmission of HIV
      and HCV and for initiation into injecting drug use in New York City, 2011-2015,
      with implications for the current opioid epidemic in the US.
AB  - OBJECTIVE: We identified potential geographic "hotspots" for drug-injecting
      transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs
      (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of
      the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage.
      METHODS: We recruited 910 PWID entering Mount Sinai Beth Israel substance use
      treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing
      were conducted. Residential ZIP codes were used as geographic units of analysis.
      Potential "hotspots" for HIV and HCV transmission were defined as 1) having
      relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive
      PWID reporting transmission risk-passing on used syringes to others, and 3)
      having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk
      injecting with previously used needles/syringes. Hotspots for injecting drug use
      initiation were defined as ZIP codes with 5 or more persons who began injecting
      within the previous 6 years. RESULTS: Among PWID, 96% injected heroin, 81% male,
      34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV
      seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP
      codes were identified as potential hotspots due to small numbers of HIV
      seropositive PWID reporting transmission risk. Four ZIP codes were identified as
      potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for
      injecting drug use initiation. DISCUSSION: For HIV, the lack of potential
      hotspots is further validation of widespread effectiveness of efforts to reduce
      injecting-related HIV transmission. Injecting-related HIV transmission is likely
      to be a rare, random event. HCV prevention efforts should include focus on
      potential hotspots for transmission and on hotspots for initiation into injecting
      drug use. We consider application of methods for the current opioid epidemic in
      the US.

PMID- 29596466
TI  - The changing relationship between marriage and childbearing in Hong Kong.
AB  - Births outside marriage (BoM) account for around 15% of all births globally.
      However, the distribution around the world is very uneven, as are cultural and
      political attitudes towards them. Studies from East Asia have shown that the
      percentage of such births is very low, with only modest increases in recent
      years. The orthodox demographic view holds that the maintenance of conservative
      views around the relationship between marriage and childbearing can play a role
      in keeping fertility low. Prenuptial pregnancies (PNP) (where births occur within
      eight months of marriage) have been identified as a growing phenomenon in Japan,
      possibly being an 'alternative' Asian pathway to family formation. As yet, no
      comprehensive statistical analysis of the trends of BoM or PNP has been performed
      for Hong Kong. Using a comprehensive microdata set of birth registration in Hong
      Kong from 1984-2015 (N = 1,680,831) we provide evidence of recent trends in such
      'alternative pathways' to family formation and examine predictors through
      regression analysis. Our results indicate, in common with elsewhere in East Asia,
      low overall period rates of either BoM or PNP (although the latter has risen
      notably in recent years). While more recent birth cohorts exhibit higher
      prevalence of such births, their incomplete nature and higher expected propensity
      suggests that the figures are exaggerated. In our regression analysis, we find
      that lower educational attainment is a strong predictor of both BoM and PNP,
      suggesting that a bifurcation of experience may be occurring. This adds further
      evidence to the theory that the maintenance of traditional family formation
      systems in the context of revolutionised educational and work opportunities for
      women mean that the opportunity costs of the 'marriage package' become too high.
      Current disparities in rights and privileges between married and unmarried
      parents-and especially their children-means that targeted family planning
      services and support for vulnerable families are policy priorities.

PMID- 29596465
TI  - Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor
      development in a mouse model of RAS-driven pancreatic cancer.
AB  - Given the frequency with which MAP kinase signaling is dysregulated in cancer,
      much effort has been focused on inhibiting RAS signaling for therapeutic benefit.
      KSR1, a pseudokinase that interacts with RAF, is a potential target; it was
      originally cloned in screens for suppressors of constitutively active RAS, and
      its deletion prevents RAS-mediated transformation of mouse embryonic fibroblasts.
      In this work, we used a genetically engineered mouse model of pancreatic cancer
      to assess whether KSR1 deletion would influence tumor development in the setting
      of oncogenic RAS. We found that Ksr1-/- mice on this background had a modest but
      significant improvement in all-cause morbidity compared to Ksr1+/+ and Ksr1+/-
      cohorts. Ksr1-/- mice, however, still developed tumors, and precursor pancreatic
      intraepithelial neoplastic (PanIN) lesions were detected within a similar
      timeframe compared to Ksr1+/+ mice. No significant differences in pERK expression
      or in proliferation were noted. RNA sequencing also did not reveal any unique
      genetic signature in Ksr1-/- tumors. Further studies will be needed to determine
      whether and in what settings KSR inhibition may be clinically useful.

PMID- 29596467
TI  - Circulating autoantibodies against neuroblastoma suppressor of tumorigenicity 1
      (NBL1): A potential biomarker for coronary artery disease in patients with
      obstructive sleep apnea.
AB  - OBJECTIVE: Although severe obstructive sleep apnea (OSA) is an important risk
      factor for atherosclerosis-related diseases including coronary artery disease
      (CAD), there is no reliable biomarker of CAD risks in patients with OSA. This
      study aimed to test our hypothesis that circulating autoantibodies against
      neuroblastoma suppressor of tumorigenicity 1 (NBL1-Abs) are associated with the
      prevalence of CAD in patients with OSA. METHODS: Eighty-two adults diagnosed with
      OSA by polysomnography, 96 patients with a diagnosis of acute coronary syndrome
      (ACS) and 64 healthy volunteers (HVs) were consecutively enrolled. Serum samples
      were collected from patients with OSA at diagnostic polysomnography and from
      patients with ACS at disease onset. Serum NBL1-Ab level was measured by amplified
      luminescence proximity homogeneous assay and its association with clinical
      variables related to atherosclerosis was evaluated. RESULTS: NBL1-Ab level was
      significantly elevated in patients with both OSA and ACS compared with HVs.
      Subgroup analyses showed that NBL1-Ab level was markedly higher in patients with
      severe OSA and OSA patients with a history of CAD. Weak associations were
      observed between NBL1-Ab level and apnea-hypopnea index, age, mean SpO2 and
      arousal index, whereas significantly higher NBL1-Ab levels were observed in OSA
      patients with a history of CAD than in those without a history of CAD.
      Sensitivity analysis using a logistic regression model also demonstrated that
      increased NBL1-Ab levels were associated with the previous history of CAD in
      patients with OSA. CONCLUSIONS: Elevated NBL1-Ab levels may be associated with
      the prevalence of CAD in patients with OSA, which needs to be confirmed further.

PMID- 29596468
TI  - Investigation of the seasonal microbiome of Anopheles coluzzii mosquitoes in
      Mali.
AB  - The poorly understood mechanisms of dry season persistence of Anopheles spp.
      mosquitoes through the dry season in Africa remain a critical gap in our
      knowledge of Plasmodium disease transmission. While it is thought that adult
      mosquitoes remain in a dormant state throughout this seven-month dry season, the
      nature of this state remains unknown and has largely not been recapitulated in
      laboratory settings. To elucidate possible connections of this state with
      microbial composition, the whole body microbiomes of adult mosquitoes in the dry
      and wet seasons in two locations of Mali with varying water availability were
      compared by sequencing the 16S ribosomal RNA gene. These locations were a village
      near the Niger River with year-round water sources (N'Gabakoro, "riparian"), and
      a typical Sahelian area with highly seasonal breeding sites (Thierola Area,
      "Sahelian"). The 16S bacterial data consisted of 2057 sequence variants in 426
      genera across 184 families. From these data, we found several compositional
      differences that were seasonally and spatially linked. Counter to our initial
      hypothesis, there were more pronounced seasonal differences in the bacterial
      microbiome of riparian, rather than Sahelian areas. These seasonal shifts were
      primarily in Ralstonia, Sphingorhabdus, and Duganella spp. bacteria that are
      usually soil and water-associated, indicating these changes may be from bacteria
      acquired in the larval environment, rather than adulthood. In Sahelian dry season
      mosquitoes, there was a unique intracellular bacteria, Anaplasma, which likely
      was acquired through non-human blood feeding. Cytochrome B analysis of blood
      meals showed greater heterogeneity in host choice of An. coluzzii independent of
      season in the Thierola area compared to N'Gabakoro (77.5% vs. 94.6% human-origin
      blood meal, respectively), indicating a relaxation of anthropophily. Overall,
      this exploratory study provides valuable indications of spatial and seasonal
      differences in bacterial composition which help refine this difficult to study
      state.

PMID- 29596469
TI  - Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the
      head and neck and is associated with an advanced tumor stage.
AB  - INTRODUCTION: The transcription factor SOX2 has been identified as a lineage
      survival oncogene in squamous cell carcinoma and copy number gain is a common
      event in several human malignancies including head and neck cancer. However, the
      regulation and function of SOX2 during carcinogenesis as well as its prognostic
      value appears to be highly context dependent. As an example, high SOX2 expression
      in lung squamous cell carcinoma (SCC) is related to a favorable prognosis, while
      it is associated with poor outcome in lung adenocarcinoma. More recently, higher
      SOX2 levels and improved survival was also reported for head and neck SCC
      (HNSCC), and silencing of SOX2 expression in HNSCC cell lines revealed a
      mesenchymal-like phenotype with prominent vimentin expression. So far, SOX2
      expression and its clinical relevance for other head and neck cancers, such as
      adenoid cystic carcinoma (HNACC) have not been sufficiently investigated.
      MATERIAL AND METHODS: SOX2, vimentin and E-cadherin expression was assessed by
      immunohistochemical staining on serial sections from formalin fixed and paraffin
      embedded tissue samples of a patient cohort (n = 45) with primary ACC and
      correlated with patient and tumor characteristics as well as survival. RESULTS:
      High SOX2 expression was found in 14 (31%) primary tumor specimens and was
      significantly correlated with a N0 lymph node status (p = 0.04), while low SOX2
      expression was correlated with a solid growth pattern (p = 0.031). Of the 45
      patients, 27 tumor samples resembled an EMT-like phenotype, as assessed by high
      vimentin and low E-cadherin levels. However, in HNACC SOX2 levels were neither
      correlated with vimentin nor with E-cadherin expression, further supporting a
      context dependent regulation and function of SOX2 in distinct tumor entities.
      CONCLUSION: The absence of SOX2 was predominantly found in solid HNACC, which are
      characterized by a more aggressive phenotype in ACC. However, the underlying
      molecular mechanisms of SOX2 regulation and function in distinct HNACC subgroups
      remain to be fully elucidated.

PMID- 29596470
TI  - Dysfunction in the mitochondrial Fe-S assembly machinery leads to formation of
      the chemoresistant truncated VDAC1 isoform without HIF-1alpha activation.
AB  - Biogenesis of iron-sulfur clusters (ISC) is essential to almost all forms of life
      and involves complex protein machineries. This process is initiated within the
      mitochondrial matrix by the ISC assembly machinery. Cohort and case report
      studies have linked mutations in ISC assembly machinery to severe mitochondrial
      diseases. The voltage-dependent anion channel (VDAC) located within the
      mitochondrial outer membrane regulates both cell metabolism and apoptosis.
      Recently, the C-terminal truncation of the VDAC1 isoform, termed VDAC1-DeltaC,
      has been observed in chemoresistant late-stage tumor cells grown under hypoxic
      conditions with activation of the hypoxia-response nuclear factor HIF-1alpha.
      These cells harbored atypical enlarged mitochondria. Here, we show for the first
      time that depletion of several proteins of the mitochondrial ISC machinery in
      normoxia leads to a similar enlarged mitochondria phenotype associated with
      accumulation of VDAC1-DeltaC. This truncated form of VDAC1 accumulates in the
      absence of HIF-1alpha and HIF-2alpha activations and confers cell resistance to
      drug-induced apoptosis. Furthermore, we show that when hypoxia and siRNA knock
      down of the ISC machinery core components are coupled, the cell phenotype is
      further accentuated, with greater accumulation of VDAC1-DeltaC. Interestingly, we
      show that hypoxia promotes the downregulation of several proteins (ISCU, NFS1,
      FXN) involved in the early steps of mitochondrial Fe-S cluster biogenesis.
      Finally, we have identified the mitochondria-associated membrane (MAM) localized
      Fe-S protein CISD2 as a link between ISC machinery downregulation and
      accumulation of anti-apoptotic VDAC1-DeltaC. Our results are the first to
      associate dysfunction in Fe-S cluster biogenesis with cleavage of VDAC1, a form
      which has previously been shown to promote tumor resistance to chemotherapy, and
      raise new perspectives for targets in cancer therapy.

PMID- 29596471
TI  - Predicting dementia from primary care records: A systematic review and meta
      analysis.
AB  - INTRODUCTION: Possible dementia is usually identified in primary care by general
      practitioners (GPs) who refer to specialists for diagnosis. Only two-thirds of
      dementia cases are currently recorded in primary care, so increasing the
      proportion of cases diagnosed is a strategic priority for the UK and
      internationally. Variables in the primary care record may indicate risk of
      developing dementia, and could be combined in a predictive model to help find
      patients who are missing a diagnosis. We conducted a meta-analysis to identify
      clinical entities with potential for use in such a predictive model for dementia
      in primary care. METHODS AND FINDINGS: We conducted a systematic search in
      PubMed, Web of Science and primary care database bibliographies. We included
      cohort or case-control studies which used routinely collected primary care data,
      to measure the association between any clinical entity and dementia. Meta
      analyses were performed to pool odds ratios. A sensitivity analysis assessed the
      impact of non-independence of cases between studies. From a sift of 3836 papers,
      20 studies, all European, were eligible for inclusion, comprising >1 million
      patients. 75 clinical entities were assessed as risk factors for all cause
      dementia, Alzheimer's (AD) and Vascular dementia (VaD). Data included were
      unexpectedly heterogeneous, and assumptions were made about definitions of
      clinical entities and timing as these were not all well described. Meta-analysis
      showed that neuropsychiatric symptoms including depression, anxiety, and
      seizures, cognitive symptoms, and history of stroke, were positively associated
      with dementia. Cardiovascular risk factors such as hypertension, heart disease,
      dyslipidaemia and diabetes were positively associated with VaD and negatively
      with AD. Sensitivity analyses showed similar results. CONCLUSIONS: These findings
      are of potential value in guiding feature selection for a risk prediction tool
      for dementia in primary care. Limitations include findings being UK-focussed.
      Further predictive entities ascertainable from primary care data, such as changes
      in consulting patterns, were absent from the literature and should also be
      explored in future studies.

PMID- 29596472
TI  - Evaluation of nationwide supplementary immunization in Lao People's Democratic
      Republic: Population-based seroprevalence survey of anti-measles and anti-rubella
      IgG in children and adults, mathematical modelling and a stability testing of the
      vaccine.
AB  - BACKGROUND: Measles outbreaks have occurred in some countries despite
      supplementary immunization activities (SIA) using measles-containing vaccine with
      high vaccination coverage. We conducted a cross-sectional seroprevalence survey
      to estimate population immunity in Lao People's Democratic Republic where
      repeated mass immunization has failed to eliminate measles. METHODS AND FINDINGS:
      In this nationwide multistage cluster sampling survey conducted in 2014 based on
      probability proportionate to size sampling, blood samples were collected from
      2,135 children and adults living in 52 randomly selected villages. Anti-measles
      and anti-rubella IgG were measured, and IgG prevalence was calculated. We applied
      mathematical modelling to estimate the number of cases of congenital rubella
      syndrome (CRS) in 2013 that were averted by the 2011 SIA. A stability testing was
      applied to the MR vaccine at 4 degrees C, 25 degrees C, and 35 degrees C to
      examine stability differences between measles and rubella vaccine components.
      Measles IgG prevalence was significantly lower in the target age groups (5-21
      years) of the 2011 SIA using a combination vaccine for measles and rubella
      vaccine (MR vaccine) than in young adults (22-39 years) (86.8% [95% CI: 83.0
      90.6] vs. 99.0% [98.3-99.8]; p<0.001), whereas rubella IgG prevalence was
      significantly higher (88.2% [84.5-91.8] vs. 74.6% [70.7-78.5]; p<0.001). In the
      SIA target age groups, prevalence of measles IgG, but not rubella IgG, increased
      with age. CRS cases prevented in 2013 ranged from 16 [0-50] to 92 [32-180] if the
      force of infection had remained unchanged or had been reduced by 75%,
      respectively. In freeze-dried conditions, the measles vaccine component was more
      heat sensitive than the rubella component. CONCLUSIONS: Inconsistent IgG
      prevalence between measles and rubella in Lao PDR can be partly explained by
      different stability of the measles and rubella vaccine components under heat
      exposure. Suboptimal vaccine handling may cause insufficient immunogenicity for
      measles, which subsequently leads to an outbreak despite high SIA coverage, while
      direct evidence is lacking. Temperature monitoring of the vaccine should be
      conducted.

PMID- 29596473
TI  - Psychoactive substances and violent offences: A retrospective analysis of
      presentations to an urban emergency department in Switzerland.
AB  - BACKGROUND: Psychoactive substances are often regarded as causal factors
      contributing to violent injuries, sexual abuse and homicides. While these effects
      have been demonstrated for some substances (e.g. cocaine), current available data
      for others are more controversial (e.g. cannabis) or very limited (e.g. ecstasy).
      AIMS OF THE STUDY: To collect data on the type and frequency of psychoactive
      substance use in cases of emergency department (ED) presentations related to
      interpersonal violence. METHODS: Retrospective study at the University Hospital
      of Bern, Switzerland, between May 2012 and June 2016. The study covered cases of
      violent crime associated with psychoactive substances. Cases of isolated ethanol
      intoxication, suicide attempts, and substance use for medical purposes were
      excluded. RESULTS: The study included 103 cases among the 164,846 ED attendances.
      In the majority of the cases, the type of violence was bodily force (52%) related
      to urban violence (83%). The mean patient age was 29 years and 79% were male. 63%
      of the patients reported use of more than one drug; alcohol co-use was reported
      in 60% of the cases. Besides alcohol, the substances most often reported were
      cannabis (50%) and cocaine (21%). Alcohol and cannabis was also the most commonly
      reported substance combination (36% of the total cases). Urine drug screening was
      performed in 34% of the cases and cannabis and cocaine were the most commonly
      detected substances (46% and 19%, respectively). There were no cases of novel
      substances. 23% of the patients were admitted to a hospital ward, 10% to a
      psychiatric clinic. CONCLUSION: Cannabis and cocaine were, besides alcohol, the
      substances most often reported in ED presentations related to offences of
      violence. Because of the high prevalence of alcohol co-use, no final conclusions
      can be drawn on the contribution of single substances.

PMID- 29596474
TI  - Phloem transport capacity of transgenic rice T1c-19 (Cry1C*) under several
      potassium fertilizer levels.
AB  - Genetic modification of Cry-proteins from Bacillus thuringiensis (Bt) is a common
      practice in economically important crops to improve insecticide resistance and
      reduce the use of pesticides. However, introduction of these genes can have
      unintended side effects, which should be closely monitored for effective breeding
      and crop management. To determine the potential cause of these negative effects,
      we explored assimilate partitioning in the transgenic Bt rice line T1c-19
      (Cry1C*), which was compared with that of its wild-type counterpart Minghui 63
      (MH63) under different potassium fertilization application treatment conditions.
      In a pot experiment, 0, 0.4, and 0.6 g K2O was applied per kg of dry soil to
      determine the phloem transport characteristics of the two rice lines. We used a
      variety of assessment indicators ranging from morphological to physiological
      aspects, including the number of large and small vascular bundles in the neck
      internode at the heading stage, the diameter and bleeding intensity of the neck
      internode at the filling stage, and the content and apparent ratio of transferred
      non-structural carbohydrates (NSC) in the culm and sheath from the heading to
      maturing stages. The K utilization and grain yield at the maturing stage were
      also concerned. Results presented that the mean setting rate and grain yield of
      T1c-19 (Cry1C*) decreased by 22.3% and 26.2% compared to those in MH63,
      respectively. Compared to MH63, the K concentration and accumulation were
      significantly higher in the culms and leaves, but significantly lower in grain of
      T1c-19 (Cry1C*). T1c-19 (Cry1C*) had less apparent NSC efflux in the culm and
      sheath, fewer small vascular bundles, and a smaller diameter and bleeding
      intensity of the neck internode than MH63. In addition, linear correlation
      analysis indicated that there were positive correlations among grain yield,
      setting rate, the apparent NSC efflux in the culm and sheath, number of small
      vascular bundles, and the neck internode diameter and bleeding intensity. These
      unintended effects may directly or indirectly be caused by insertion of exogenous
      Bt (Cry1C*) gene, which should be further considered in the future breeding of
      transgenic crops.

PMID- 29596475
TI  - Sensitivity of different MRI sequences in the early detection of melanoma brain
      metastases.
AB  - BACKGROUND: After the emergence of new MRI techniques such as susceptibility- and
      diffusion-weighted imaging (SWI and DWI) and because of specific imaging
      characteristics of melanoma brain metastases (MBM), it is unclear which MRI
      sequences are most beneficial for detection of MBM. This study was performed to
      investigate the sensitivity of six clinical MRI sequences in the early detection
      of MBM. METHODS: Medical records of all melanoma patients referred to our center
      between November 2005 and December 2016 were reviewed for presence of MBM.
      Analysis encompassed six MRI sequences at the time of initial diagnosis of first
      or new MBM, including non-enhanced T1-weighted (T1w), contrast-enhanced T1w
      (ceT1w), T2-weighted (T2w), T2w-FLAIR, susceptibility-weighted (SWI) and
      diffusion-weighted (DWI) MRI. Each lesion was rated with respect to its
      conspicuity (score from 0-not detectable to 3-clearly visible). RESULTS: Of 1210
      patients, 217 with MBM were included in the analysis and up to 5 lesions per
      patient were evaluated. A total of 720 metastases were assessed and all six
      sequences were available for 425 MBM. Sensitivity (conspicuity >=2) was 99.7% for
      ceT1w, 77.0% for FLAIR, 64.7% for SWI, 61.0% for T2w, 56.7% for T1w, and 48.4%
      for DWI. Thirty-one (7.3%) of 425 lesions were only detectable by ceT1w but no
      other sequence. CONCLUSIONS: Contrast-enhanced T1-weighting is more sensitive
      than all other sequences for detection of MBM. Disruption of the blood-brain
      barrier is consistently an earlier sign in MBM than perifocal edema, signal loss
      on SWI or diffusion restriction.

PMID- 29596476
TI  - The colonic epithelium plays an active role in promoting colitis by shaping the
      tissue cytokine profile.
AB  - Inflammatory bowel disease (IBD) is a chronic condition driven by loss of
      homeostasis between the mucosal immune system, the commensal gut microbiota, and
      the intestinal epithelium. Our goal is to understand how these components of the
      intestinal ecosystem cooperate to control homeostasis. By combining quantitative
      measures of epithelial hyperplasia and immune infiltration with multivariate
      analysis of inter- and intracellular signaling, we identified epithelial
      mammalian target of rapamycin (mTOR) signaling as a potential driver of
      inflammation in a mouse model of colitis. A kinetic analysis of mTOR inhibition
      revealed that the pathway regulates epithelial differentiation, which in turn
      controls the cytokine milieu of the colon. Consistent with our in vivo analysis,
      we found that cytokine expression of organoids grown ex vivo, in the absence of
      bacteria and immune cells, was dependent on differentiation state. Our study
      suggests that proper differentiation of epithelial cells is an important feature
      of colonic homeostasis because of its effect on the secretion of inflammatory
      cytokines.

PMID- 29596477
TI  - Using support vector machines on photoplethysmographic signals to discriminate
      between hypovolemia and euvolemia.
AB  - Identifying trauma patients at risk of imminent hemorrhagic shock is a
      challenging task in intraoperative and battlefield settings given the variability
      of traditional vital signs, such as heart rate and blood pressure, and their
      inability to detect blood loss at an early stage. To this end, we acquired N = 58
      photoplethysmographic (PPG) recordings from both trauma patients with suspected
      hemorrhage admitted to the hospital, and healthy volunteers subjected to blood
      withdrawal of 0.9 L. We propose four features to characterize each recording:
      goodness of fit (r2), the slope of the trend line, percentage change, and the
      absolute change between amplitude estimates in the heart rate frequency range at
      the first and last time points. Also, we propose a machine learning algorithm to
      distinguish between blood loss and no blood loss. The optimal overall accuracy of
      discriminating between hypovolemia and euvolemia was 88.38%, while sensitivity
      and specificity were 88.86% and 87.90%, respectively. In addition, the proposed
      features and algorithm performed well even when moderate blood volume was
      withdrawn. The results suggest that the proposed features and algorithm are
      suitable for the automatic discrimination between hypovolemia and euvolemia, and
      can be beneficial and applicable in both intraoperative/emergency and combat
      casualty care.

PMID- 29596478
TI  - Association of socioeconomic status with hearing loss in Chinese working-aged
      adults: A population-based study.
AB  - Hearing loss is the most common sensory impairment, but limited studies focused
      on the association of socioeconomic status (SES) with hearing loss among adults
      of working age. This paper aimed to fill this gap among Chinese adults. We
      obtained data from Ear and Hearing Disorder Survey conducted in four provinces of
      China in 2014-2015. The survey was based on WHO Ear and Hearing Disorders Survey
      Protocol and 25,860 adults aged 25 to 59 years were selected in this study.
      Trained local examiners performed pure tone audiometry to screen people with
      hearing loss, and those who were screened positively for hearing loss were
      referred to audiologists to make final diagnosis. SES was measured by occupation,
      education and income. Results show after adjusting for SES measures and
      covariates, in urban areas, compared with white-collar workers, blue-collar
      workers and the unemployed were more likely to have hearing loss, with an odds
      ratio of 1.2 (95%CI: 1.0, 1.3) and 1.2 (95%CI: 1.0, 1.4), respectively. Compared
      with people with education of senior high school or above, those with junior high
      school, primary school and illiteracy had 1.6 (95%CI: 1.4, 1.8), 2.1(95%CI: 1.7,
      2.5) and 2.6 (95%CI: 1.9, 3.7) times as likely to have hearing loss,
      respectively. In rural areas, the unemployed had 1.5 (95%CI: 1.0, 2.3) times the
      risk of hearing loss compared with white-collar workers, and illiterates had 1.6
      (95%CI: 1.6, 2.1) times the risk of hearing loss compared with people with
      education of senior high school or above, after SES variables and covariates were
      taken into considerations. Income was not significantly associated with hearing
      loss in urban and rural areas. In conclusion, SES, in the form of occupation and
      education, was associated with hearing loss among working-aged population, and
      further studies are needed to explore the mechanism of such association.

PMID- 29596479
TI  - The immediate effects of a single autogenic drainage session on ventilatory
      mechanics in adult subjects with cystic fibrosis.
AB  - INTRODUCTION: The aim of this study was to gain insight into the physiological
      changes occurring in subjects with cystic fibrosis (CF) after autogenic drainage
      (AD). Changes in respiratory system resistance (Rrs), reactance (Xrs), and
      spirometry were analyzed in adult CF subjects after a single AD physiotherapy
      session. METHODS: This prospective observational study was conducted during the
      annual check-up of adult CF subjects in stable condition. Spirometry and Rrs and
      Xrs measurements using the forced oscillations technique at 5, 11, and 19 hertz
      (Hz) were performed before and 30 min after a 20-min AD session. Control CF
      subjects were tested at baseline and 50 min without AD. Results are expressed as
      mean +/- standard deviation or median [interquartile range]. RESULTS: Thirty
      subjects were included in the physiotherapy group (age 29 [25-34] years, forced
      expiratory volume in 1 s (FEV1) 40.3 [30.1-57.9]% predicted) and 11 in the
      control group (age 31 [28.5-36.5] years, FEV1 43.6 [31.1-51.9] % predicted). No
      significant changes in any parameter were observed in the control group. AD
      modestly but significantly increased the forced vital capacity (FVC) and FEV1
      (p<0.001). Inspiratory resistance was also significantly improved by AD: Rrs5
      from 5.74+/-2.39 to 5.24+/-2.17 cmH2O/L/s, p<0.05; Rrs11 from 4.83+/-1.98 to
      4.32+/-1.7 cmH2O/L/s, p = 0.003; and Rrs19 from 4.18 [3.46-5.07] to 3.86 [2.76
      4.98] cmH2O/L/s, p<0.001. In contrast, AD had no significant effects on frequency
      dependence of resistance (Rrs5-Rrs19) or expiratory resistance. Inspiratory Xrs5,
      but not DeltaXrs5 (expiratory-inspiratory Xrs), was improved by AD (p<0.05).
      Moderate correlations were detected between the improvement in FEV1 and FVC and
      inspiratory resistance (r = 0.53, p = 0.005 and r = 0.44, p = 0.02,
      respectively). CONCLUSION: A single session of AD improved inspiratory airway
      resistance, except in the distal airways. The forced oscillations technique
      provides a new tool for understanding the pathophysiological effects of airway
      clearance physiotherapy in CF.

PMID- 29596480
TI  - Effect of knee angle on neuromuscular assessment of plantar flexor muscles: A
      reliability study.
AB  - INTRODUCTION: This study aimed to determine the intra- and inter-session
      reliability of neuromuscular assessment of plantar flexor (PF) muscles at three
      knee angles. METHODS: Twelve young adults were tested for three knee angles (90
      degrees , 30 degrees  and 0 degrees ) and at three time points separated by 1
      hour (intra-session) and 7 days (inter-session). Electrical (H reflex, M wave)
      and mechanical (evoked and maximal voluntary torque, activation level) parameters
      were measured on the PF muscles. Intraclass correlation coefficients (ICC) and
      coefficients of variation were calculated to determine intra- and inter-session
      reliability. RESULTS: The mechanical measurements presented excellent (ICC>0.75)
      intra- and inter-session reliabilities regardless of the knee angle considered.
      The reliability of electrical measurements was better for the 90 degrees  knee
      angle compared to the 0 degrees  and 30 degrees  angles. CONCLUSIONS: Changes in
      the knee angle may influence the reliability of neuromuscular assessments, which
      indicates the importance of considering the knee angle to collect consistent
      outcomes on the PF muscles.

PMID- 29596481
TI  - Neck dissection does not increases the risk of stroke in thyroid cancer: A
      national cohort study.
AB  - OBJECTIVES: The purpose of this study is to evaluate the risk of stroke
      (hemorrhagic or ischemic) after neck dissection in thyroid cancer patients in
      Korea using national cohort data. METHODS: Using the national cohort study from
      the Korean Health Insurance Review and Assessment Service, patients with neck
      dissection for thyroid cancer (1,041) and control participants (4,164) were
      selected and matched 1:4 (age, gender, income, and region of residence). The Chi
      square test, Fischer's exact test, and the Cox-proportional hazard model were
      used. The Cox-proportional analysis used a crude model and an adjusted model for
      age, gender, income, region of residence, hypertension, diabetes, dyslipidemia.
      RESULTS: None of the participants had suffered hemorrhagic stroke in the neck
      dissection group, while 0.3% (13/4,164) of participants had suffered hemorrhagic
      stroke in the control group (P = 0.085). In total, 0.8% (8/1,041) of participants
      had suffered an ischemic stroke in the neck dissection group, and 0.7% (31/4,133)
      of participants had suffered an ischemic stroke in the control group (P = 0.936).
      The adjusted hazard ratio for ischemic stroke after neck dissection was 1.06 (95%
      confidence interval [CI] = 0.49-2.31, P = 0.884). CONCLUSION: The risk of
      hemorrhagic or ischemic stroke was not higher in thyroid cancer patients who
      underwent neck dissection than that in the matched control group.

PMID- 29596482
TI  - Home range utilization by chacma baboon (Papio ursinus) troops on Suikerbosrand
      Nature Reserve, South Africa.
AB  - Rapid urbanization coupled with decreasing areas of natural habitat are causing
      baboon populations to become scattered and isolated, often resulting in increased
      levels of human-baboon conflict. To implement baboon-human conflict management
      strategies, it is essential to formulate realistic conservation policies that
      deal with all stakeholder concerns and ensure the conservation of viable baboon
      populations. A study was initiated in response to complaints of perceived
      excessive baboon numbers and associated lack of food resources on Suikerbosrand
      Nature Reserve in South Africa. Data obtained from GPS tracking collars fitted to
      one baboon from each of 10 identified troops were analyzed to determine home
      range size and utilization. The spatial representation of home ranges generated
      from this study will allow reserve management to identify areas of potential high
      and low human-baboon conflict and will contribute to the development of a formal
      baboon management plan to reduce human-baboon conflict on and around the reserve.
      Home ranges were unevenly distributed and had a mean size of 26.72 km2 +/- 13.91
      SD in the cold/dry season and 26.54 km2 +/- 12.76 SD in the warm/wet season.
      Troop home ranges overlapped to some degree and five troops utilized areas
      outside the reserve. Although no significant relationship between troop size and
      home range was found, there was a positive relationship between troop size and
      daily distance travelled. All troops had significantly longer mean daily
      distances during the warm/wet season than during the cold/dry season (P <= 0.02).

PMID- 29596483
TI  - Development of post-disaster psychosocial evaluation and intervention for
      children: Results of a South Korean delphi panel survey.
AB  - OBJECTIVE: This study aimed to administer a Delphi panel survey and provide
      evidence for the development of a psychological intervention protocol for use
      after disasters in South Korea. METHOD: A three-round Delphi survey was
      conducted. In all rounds, respondents answered open- or closed-ended questions
      regarding their views on i) the concept of disaster, ii) evaluation, iii)
      intervention, and iv) considerations in a disaster. Data from Round 1 were
      subjected to content analysis. In Round 2, items with content validity ratios
      (CVRs) greater than 0.49 were included, and in Round 3, items with a CVR>=0.38
      were accepted. RESULTS: The response rates for the Delphi survey were high: 83%
      (n = 15, Round 1), 80% (n = 16, Round 2), and 86% (n = 24, Round 3). The data
      collected during this survey showed a need for a support system for children; for
      preventive strategies, including disaster readiness plans; for the protection of
      children's safety; and for the development of post-disaster psychosocial care.
      CONCLUSIONS: The panel experts reached a consensus regarding the steps they
      considered critical in post-disaster evaluation and intervention. The findings
      suggest a unified model for advancing the development of the Korean version of an
      intervention protocol for children and adolescents exposed to traumatic events.

PMID- 29596484
TI  - First quantification of subtidal community structure at Tristan da Cunha Islands
      in the remote South Atlantic: from kelp forests to the deep sea.
AB  - Tristan da Cunha Islands, an archipelago of four rocky volcanic islands situated
      in the South Atlantic Ocean and part of the United Kingdom Overseas Territories
      (UKOTs), present a rare example of a relatively unimpacted temperate marine
      ecosystem. We conducted the first quantitative surveys of nearshore kelp forests,
      offshore pelagic waters and deep sea habitats. Kelp forests had very low
      biodiversity and species richness, but high biomass and abundance of those
      species present. Spatial variation in assemblage structure for both nearshore
      fish and invertebrates/algae was greatest between the three northern islands and
      the southern island of Gough, where sea temperatures were on average 3-4o colder.
      Despite a lobster fishery that provides the bulk of the income to the Tristan
      islands, lobster abundance and biomass are comparable to or greater than many
      Marine Protected Areas in other parts of the world. Pelagic camera surveys
      documented a rich biodiversity offshore, including large numbers of juvenile blue
      sharks, Prionace glauca. Species richness and abundance in the deep sea is
      positively related to hard rocky substrate and biogenic habitats such as sea
      pens, crinoids, whip corals, and gorgonians were present at 40% of the deep
      camera deployments. We observed distinct differences in the deep fish community
      above and below ~750 m depth. Concurrent oceanographic sampling showed a
      discontinuity in temperature and salinity at this depth. While currently healthy,
      Tristan's marine ecosystem is not without potential threats: shipping traffic
      leading to wrecks and species introductions, pressure to increase fishing effort
      beyond sustainable levels and the impacts of climate change all could potentially
      increase in the coming years. The United Kingdom has committed to protection of
      marine environments across the UKOTs, including Tristan da Cunha and these
      results can be used to inform future management decisions as well as provide a
      baseline against which future monitoring can be based.

PMID- 29596485
TI  - Predicting financial market crashes using ghost singularities.
AB  - We analyse the behaviour of a non-linear model of coupled stock and bond prices
      exhibiting periodically collapsing bubbles. By using the formalism of dynamical
      system theory, we explain what drives the bubbles and how foreshocks or
      aftershocks are generated. A dynamical phase space representation of that system
      coupled with standard multiplicative noise rationalises the log-periodic power
      law singularity pattern documented in many historical financial bubbles. The
      notion of 'ghosts of finite-time singularities' is introduced and used to
      estimate the end of an evolving bubble, using finite-time singularities of an
      approximate normal form near the bifurcation point. We test the forecasting skill
      of this method on different stochastic price realisations and compare with Monte
      Carlo simulations of the full system. Remarkably, the approximate normal form is
      significantly more precise and less biased. Moreover, the method of ghosts of
      singularities is less sensitive to the noise realisation, thus providing more
      robust forecasts.

PMID- 29596486
TI  - Psychometric properties of the Czech version of the Stigma Scale of Epilepsy.
AB  - Although significant attention has been devoted to analyzing stigma associated
      with epilepsy, there is still a significant lack of valid and reliable
      instruments. We aimed to validate the 23-item Czech version of the Stigma Scale
      of Epilepsy (SSE; originally developed in Brazil), which has been used to
      evaluate epilepsy-related stigma in the general population. Verification of the
      SSE questionnaire was carried out in a group of 207 students aged 15-18 years of
      whom none had epilepsy. These students completed the SSE twice in a period of 3-6
      months as part of standard test-retest evaluation practice. The instrument
      exhibits good psychometric properties including internal consistency higher than
      in the original version (Cronbach's alpha of 0.856 here compared with 0.81
      reported in Brazil) and acceptable test-retest reliability. Using exploratory
      factor analysis (not provided for the original version), four factors were
      identified and corresponding subscales were described and interpreted. Two items
      did not fit into the structure and were eliminated. Confirmatory factor analysis
      was used to propose and verify the hierarchical 4-factor structure of the Czech
      version of SSE confirming the existence of a common factor corresponding to
      stigma. The results showed that the Czech version of SSE has good psychometric
      properties and can be used in further research and clinical practice.

PMID- 29596487
TI  - Involvement of the olfactory system in the induction of anti-fatigue effects by
      odorants.
AB  - Some components of the neural circuits underlying innate odor-evoked responses
      have recently been elucidated. Odor information detected by the olfactory
      receptors is transmitted from the olfactory bulb to the cortical amygdala, where
      physiological and emotional states such as attraction or avoidance are
      controlled. Thus, activation of specific olfactory receptors can elicit changes
      in physiological and/or psychological state. Here, we examined on the odorant Hex
      Hex Mix, which has been reported to induce anti-fatigue effects. Fatigue is a
      prevalent condition that is often related to overwork and psychological stress.
      Various anti-fatigue treatments have been developed, including supplements and
      odorants. However, the mechanisms underlying the anti-fatigue effects of these
      substances are currently unclear. In the present study, we analyzed the
      involvement of the olfactory system in the mechanisms underlying this effect. We
      identified the human olfactory receptors activated by Hex-Hex Mix, and evaluated
      whether activation of these olfactory receptors by a newly developed odorant
      elicited a similar anti-fatigue effect to Hex-Hex Mix. We assessed anti-fatigue
      effects with behavioral tests, and 17 healthy males performed the 2-back test as
      a fatigue-inducing task with or without exposure to the new odorant. Immediately
      before and after the task, participants performed a cognitive task to evaluate
      their level of mental fatigue. We found that the difference value of the correct
      response rate on the cognitive task in the evaluation session was significantly
      different between in the odorant condition and in the without-odorant condition
      during the fatigue-inducing session suggesting that the new odorant may improve
      performance in the fatigue-inducing condition. The results indicated that the new
      odorant activates the same olfactory receptors as Hex-Hex Mix, which has been
      reported to induce anti-fatigue effects. Our findings suggest that the olfactory
      receptors in the olfactory system may be involved in the attenuation of fatigue.

PMID- 29596488
TI  - Understanding a successful obesity prevention initiative in children under 5 from
      a systems perspective.
AB  - INTRODUCTION/BACKGROUND: Systems thinking represents an innovative and logical
      approach to understanding complexity in community-based obesity prevention
      interventions. We report on an approach to apply systems thinking to understand
      the complexity of a successful obesity prevention intervention in early childhood
      (children aged up to 5 years) conducted in a regional city in Victoria,
      Australia. METHODS: A causal loop diagram (CLD) was developed to represent system
      elements related to a successful childhood obesity prevention intervention in
      early childhood. Key stakeholder interviews (n = 16) were examined
      retrospectively to generate purposive text data, create microstructures, and form
      a CLD. RESULTS: A CLD representing key stakeholder perceptions of a successful
      intervention comprised six key feedback loops explaining changes in project
      implementation over time. The loops described the dynamics of collaboration,
      network formation, community awareness, human resources, project clarity, and
      innovation. CONCLUSION: The CLD developed provides a replicable means to capture,
      evaluate and disseminate a description of the dynamic elements of a successful
      obesity prevention intervention in early childhood.

PMID- 29596490
TI  - Critical in vivo roles of WNT10A in wound healing by regulating collagen
      expression/synthesis in WNT10A-deficient mice.
AB  - BACKGROUND: We have reported that WNT10A plays a critical role in the growth of
      fibroblasts/myofibroblasts and microvascular endothelial cells, i.e.; wound
      healing/scarring. To ascertain the in vivo regulatory, central functions of
      WNT10A, we examined the net effects of WNT10A depletion using WNT10A-deficient
      mice (WNT10A-/-). METHODS AND RESULTS: We generated WNT10A-/-mice, displaying a
      range of unique phenotypes of morpho/organogenetic failure, such as growth
      retardation, alopecia, kyphosis and infertility, and then focused on the
      functions of WNT10A in wound healing. We subjected C57BL/6J wild-type (WT) or
      WNT10A-/-mice to skin ulcer formation. The WNT10A-/-mice had significantly larger
      injured areas and delayed wound healing, which were associated with (a) a smaller
      number of fibroblasts/myofibroblasts and microvessels; and (b) more reduced
      expression and synthesis of collagen, compared with WT mice with intact WNT10A
      expression, especially in those with activated myofibroblasts. CONCLUSIONS: These
      observations indicate that WNT10A signaling can play a pivotal in vivo role in
      wound healing by regulating the expression and synthesis of collagen, as one of
      fibrogenic factors, at least in part, and critical in vivo roles of WNT10A
      mediated effective wound healing are extremely closely associated with collagen
      expression.

PMID- 29596489
TI  - A Boolean network of the crosstalk between IGF and Wnt signaling in aging
      satellite cells.
AB  - Aging is a complex biological process, which determines the life span of an
      organism. Insulin-like growth factor (IGF) and Wnt signaling pathways govern the
      process of aging. Both pathways share common downstream targets that allow
      competitive crosstalk between these branches. Of note, a shift from IGF to Wnt
      signaling has been observed during aging of satellite cells. Biological
      regulatory networks necessary to recreate aging have not yet been discovered.
      Here, we established a mathematical in silico model that robustly recapitulates
      the crosstalk between IGF and Wnt signaling. Strikingly, it predicts critical
      nodes following a shift from IGF to Wnt signaling. These findings indicate that
      this shift might cause age-related diseases.

PMID- 29596492
TI  - The prevalence of Yersinia enterocolitica in game animals in Poland.
AB  - Natural reservoirs of Yersinia (Y.) enterocolitica comprise different animal
      species, but little is known about the role of wild animals in the epidemiology
      of yersiniosis. The aim of the study was to evaluate the prevalence of Y.
      enterocolitica among game animals in Poland. The bio-serotypes and the
      pathogenicity markers of the analyzed isolates were determined. The experimental
      material comprised rectal swabs from 857 free-living animals hunter-harvested
      over a period of 2 years (2013-2014) in hunting districts across Poland. The
      isolates from bacteriological studies were confirmed by PCR and bio-serotyped
      based on the results of biochemical and agglutination tests. In the group of the
      218 analyzed isolates of Y. enterocolitica, 133 were derived from wild boars, 70
      from red deer, 11 from roe deer and 4 from fallow deer, and they accounted for
      61.0%, 32.1%, 5.1% and 1.8% of all isolates, respectively. Bio-serotyping assays
      revealed that 91.7% of the examined isolates belonged to biotype 1A (200/218).
      The remaining 18 isolates belonged to bio-serotypes 1B/NI (3/218, 1.4%), 1B/O:8
      (1/218, 0.5%), 2/NI (6/218, 2.8%), 2/O:27 (1/218, 0.5%), 2/O:3 (1/218, 0.5%),
      2/O:9 (2/218, 0.9%), 3/NI (2/218, 0.9%), 4/O:3 (1/218, 0.5%) and 4/O:9 (1/218,
      0.5%). The ail gene, a suggestive virulence gene for Y. enterocolitica, has been
      found in 30 isolates from 20 wild boars, in 6 isolates from red deer, and in 1
      isolate from roe deer. Our study demonstrated that Y. enterocolitica is
      frequently isolated from game animals in Poland, which poses a risk of spreading
      these infectious agents to other animal species and humans.

PMID- 29596491
TI  - Core and skin temperature influences on the surface electromyographic responses
      to an isometric force and position task.
AB  - The large body of work demonstrating hyperthermic impairment of neuromuscular
      function has utilized maximal isometric contractions, but extrapolating these
      findings to whole-body exercise and submaximal, dynamic contractions may be
      problematic. We isolated and compared core and skin temperature influences on an
      isometric force task versus a position task requiring dynamic maintenance of
      joint angle. Surface electromyography (sEMG) was measured on the flexor carpi
      radialis at 60% of baseline maximal voluntary contraction while either pushing
      against a rigid restraint (force task) or while maintaining a constant wrist
      angle and supporting an equivalent inertial load (position task). Twenty
      participants performed each task at 0.5 degrees C rectal temperature (Tre)
      intervals while being passively heated from 37.1+/-0.3 degrees C to >=1.5 degrees
      C Tre and then cooled to 37.8+/-0.3 degrees C, permitting separate analyses of
      core versus skin temperature influences. During a 3-s contraction, trend analysis
      revealed a quadratic trend that peaked during hyperthermia for root-mean-square
      (RMS) amplitude during the force task. In contrast, RMS amplitude during the
      position task remained stable with passive heating, then rapidly increased with
      the initial decrease in skin temperature at the onset of passive cooling (p =
      0.010). Combined hot core and hot skin elicited shifts toward higher frequencies
      in the sEMG signal during the force task (p = 0.003), whereas inconsistent
      changes in the frequency spectra occurred for the position task. Based on the
      patterns of RMS amplitude in response to thermal stress, we conclude that core
      temperature was the primary thermal afferent influencing neuromuscular response
      during a submaximal force task, with minimal input from skin temperature.
      However, skin temperature was the primary thermal afferent during a position task
      with minimal core temperature influence. Therefore, temperature has a task
      dependent impact on neuromuscular responses.

PMID- 29596493
TI  - Micronutrient adequacy is poor, but not associated with stunting between 12-24
      months of age: A cohort study findings from a slum area of Bangladesh.
AB  - The prevalence of stunting among children below 5 years of age is higher in the
      slum-dwelling population of Bangladesh compared to that in both urban and rural
      areas. Studies have reported that several factors such as inadequate nutrition,
      low socio-economic status, poor hygiene and sanitation and lack of maternal
      education are the substantial predictors of childhood stunting. Almost all these
      factors are universally present in the slum-dwelling population of Bangladesh.
      However, few studies have prospectively examined such determinants of stunting
      among slum populations. In this paper, we reveal the findings of a cohort study
      with an aim to explore the status of micronutrient adequacy among such vulnerable
      children and establish its association with stunting along with other
      determinants. Two-hundred-sixty-five children were enrolled and followed since
      birth until 24 months of age. We collected anthropometric, morbidity and dietary
      intake data monthly. We used the 24-hour multiple-pass recall approach to collect
      dietary intake data from the age of 9 months onward. Micronutrient adequacy of
      the diet was determined by the mean adequacy ratio (MAR) which was constructed
      from the average intake of 9 vitamins and 4 minerals considered for the analysis.
      We used generalized estimating equation (GEE) regression models to establish the
      determinants of stunting between 12-24 months of age in our study population. The
      prevalence of low-birth-weight (LBW) was about 28.7% and approximately half of
      the children were stunted by the age of 24 months. The average micronutrient
      intake was considerably lower than the recommended dietary allowance and the MAR
      was only 0.48 at 24 months of age compared to the optimum value of 1. However,
      the MAR was not associated with stunting between 12-24 months of age. Rather, LBW
      was the significant determinant (AOR = 3.03, 95% CI: 1.69-5.44) after adjusting
      for other factors such as age (AOR = 2.12, 95% CI: 1.45-3.11 at 24 months and AOR
      = 1.97, 95% CI: 1.49-2.59 at 18 months, ref: 12 months) and sex (AOR = 1.98, 95%
      CI: 1.17-3.33, ref: female). Improving the nutritional quality of complementary
      food in terms of adequacy of micronutrients is imperative for optimum growth but
      may not be adequate to mitigate under-nutrition in this setting. Further research
      should focus on identifying multiple strategies that can work synergistically to
      diminish the burden of stunting in resource-poor settings.

PMID- 29596494
TI  - High rates of chronic HBV genotype E infection in a group of migrants in Italy
      from West Africa: Virological characteristics associated with poor immune
      clearance.
AB  - Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people,
      and its presence is more commonly associated with the development of chronic HBV
      (CHB) infection. Moreover, an epidemiological link has been found between the
      distribution of HBV genotype E infection and African countries with high
      incidences of hepatocellular carcinoma. As part of a programme for the health
      assessment of migrants, we evaluated 358 young African subjects for HBV
      infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25.5%) had
      CHB. Eighty-one percent of the CHB subjects were infected with HBV genotype E,
      with a median serum HBV-DNA of 3.2 (IQR: 2.7-3.6) logIU/ml. All patients had high
      serum HBsAg titres (10,899 [range 5,359-20,272] IU/ml), and no correlation was
      found between HBsAg titres and HBV-DNA plasma levels. RT sequence analysis showed
      the presence of a number of immune escape mutations: strains from all of the
      patients had a serine at HBsAg position 140; 3 also had T116N, Y100C, and
      P142L+S143L substitutions; and 1 had a G112R substitution. Six (18%) patients had
      stop-codons at position 216. In 5 of the 9 (26.5%) CHB patients, ultrasound liver
      biopsy, quantification of total intrahepatic HBV-DNA and cccDNA, and RT/HBsAg
      sequencing were performed. The median (IQR) total intrahepatic HBV-DNA was 766
      (753-1139) copies/1000 cells, and the median (IQR) cccDNA was 17 (10-27)
      copies/1000 cells. Correlations were observed for both total intrahepatic HBV-DNA
      and cccDNA with serum HBV-DNA, while no correlation was found for the HBsAg
      titres. A difference of 2.5/1,000 nucleotides was found in the HBsAg sequences
      obtained from plasma and from liver tissue, with 3 cases of possible viral
      anatomical compartmentalization. In conclusion, a high rate of CHB infection due
      to the E genotype was demonstrated in a group of immigrants from Western Africa.
      An analysis of the viral strains obtained showed the virological characteristics
      of immune escape, which may be the cause of viral replication persistence.
      Moreover, a fair percentage of stop codon mutations were found. The lack of
      correlation between HBsAg titres and plasma or intrahepatic HBV-DNA found in
      these subjects suggests a pathway of virus production that is not linked to HBsAg
      secretion. Studies with a larger number of patients with CHB due to the E
      genotype are advisable to corroborate these observations.

PMID- 29596496
TI  - Radiogenomics analysis identifies correlations of digital mammography with
      clinical molecular signatures in breast cancer.
AB  - In breast cancer, well-known gene expression subtypes have been related to a
      specific clinical outcome. However, their impact on the breast tissue phenotype
      has been poorly studied. Here, we investigate the association of imaging data of
      tumors to gene expression signatures from 71 patients with breast cancer that
      underwent pre-treatment digital mammograms and tumor biopsies. From digital
      mammograms, a semi-automated radiogenomics analysis generated 1,078 features
      describing the shape, signal distribution, and texture of tumors along their
      contralateral image used as control. From tumor biopsy, we estimated the
      OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then,
      we used multivariate analysis under stringent cross-validation to train models
      predicting recurrence scores. Few univariate features reached Spearman
      correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded
      significantly correlated models for both signatures (correlation of OncotypeDX =
      0.49 +/- 0.07 and PAM50 = 0.32 +/- 0.10 in stringent cross-validation and
      OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained
      from the unaffected contralateral breast were not correlated suggesting that the
      image signatures were tumor-specific and that overfitting was not a considerable
      issue. We also noted that models were improved by combining clinical information
      (triple negative status and progesterone receptor). The models used mostly
      wavelets and fractal features suggesting their importance to capture tumor
      information. Our results suggest that molecular-based recurrence risk and breast
      cancer subtypes have observable radiographic phenotypes. To our knowledge, this
      is the first study associating mammographic information to gene expression
      recurrence signatures.

PMID- 29596495
TI  - Assessing the influence of health systems on Type 2 Diabetes Mellitus awareness,
      treatment, adherence, and control: A systematic review.
AB  - BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is reported to affect one in 11
      adults worldwide, with over 80% of T2DM patients residing in low-to-middle-income
      countries. Health systems play an integral role in responding to this increasing
      global prevalence, and are key to ensuring effective diabetes management. We
      conducted a systematic review to examine the health system-level factors
      influencing T2DM awareness, treatment, adherence, and control. METHODS AND
      FINDINGS: A protocol for this study was published on the PROSPERO international
      prospective register of systematic reviews (PROSPERO 2016: CRD42016048185).
      Studies included in this review reported the effects of health systems factors,
      interventions, policies, or programmes on T2DM control, awareness, treatment, and
      adherence. The following databases were searched on 22 February 2017: Medline,
      Embase, Global health, LILACS, Africa-Wide, IMSEAR, IMEMR, and WPRIM. There were
      no restrictions on date, language, or study designs. Two reviewers independently
      screened studies for eligibility, extracted the data, and screened for risk of
      bias. Thereafter, we performed a narrative synthesis. A meta-analysis was not
      conducted due to methodological heterogeneity across different aspects of
      included studies. 93 studies were included for qualitative synthesis; 7 were
      conducted in LMICs. Through this review, we found two key health system barriers
      to effective T2DM care and management: financial constraints faced by the patient
      and limited access to health services and medication. We also found three health
      system factors that facilitate effective T2DM care and management: the use of
      innovative care models, increased pharmacist involvement in care delivery, and
      education programmes led by healthcare professionals. CONCLUSIONS: This review
      points to the importance of reducing, or possibly eliminating, out-of-pocket
      costs for diabetes medication and self-monitoring supplies. It also points to the
      potential of adopting more innovative and integrated models of care, and the
      value of task-sharing of care with pharmacists. More studies which identify the
      effect of health system arrangements on various outcomes, particularly awareness,
      are needed.

PMID- 29596497
TI  - Social ecological factors and intimate partner violence in pregnancy.
AB  - BACKGROUND: Intimate partner violence (IPV) during pregnancy increases adverse
      pregnancy outcomes. Knowledge of societal, community, family and individual
      related factors associated with IPV in pregnancy is limited in Ethiopia. Our
      study examined these factors in an Ethiopian context. MATERIALS AND METHODS: A
      cross sectional study was conducted among pregnant women attending antenatal care
      at governmental health institutions, using a consecutive probability sampling
      strategy. A total of 720 pregnant women were interviewed by five trained nurses
      or midwives, using a standardized and /pretested survey questionnaire. Bivariate
      and multivariate logistic regression analyses were applied to assess factors
      contributing to IPV. We used Akaike's information criteria, to identify the model
      that best describes the factors influencing IPV in pregnancy. RESULTS: Among the
      women interviewed, physical IPV was reported by 35.6%, and lifetime emotional or
      physical abuse by 81.0%. Perceiving violence as a means to settle interpersonal
      conflicts, presence of supportive attitudes of wife beating in the society,
      regarding violence as an expression of masculinity, and presence of strict gender
      role differences in the society, were all positively associated to IPV in
      pregnancy. The presence of groups legitimizing men's violence in the community,
      feeling isolated, having no social support for victims, and presence of high
      unemployment, were the perceived community related factors positively associated
      with IPV in pregnancy. CONCLUSION: IPV in pregnancy is very prevalent in Ethiopia
      and is associated with multiple social ecologic factors. Reduction of IPV in
      pregnancy calls for cross sectorial efforts from stakeholders at different
      levels.

PMID- 29596498
TI  - Analyses of genome wide association data, cytokines, and gene expression in
      African-Americans with benign ethnic neutropenia.
AB  - BACKGROUND: Benign ethnic neutropenia (BEN) is a hematologic condition associated
      with people of African ancestry and specific Middle Eastern ethnic groups. Prior
      genetic association studies in large population showed that rs2814778 in Duffy
      Antigen Receptor for Chemokines (DARC) gene, specifically DARC null red cell
      phenotype, was associated with BEN. However, the mechanism of this red cell
      phenotype leading to low white cell count remained elusive. METHODS: We conducted
      an extreme phenotype design genome-wide association study (GWAS), analyzed ~16
      million single nucleotide polymorphisms (SNP) in 1,178 African-Americans
      individuals from the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) study and replicated from 819 African-American participants in the
      Atherosclerosis Risk in Communities (ARIC) study. Conditional analyses on
      rs2814778 were performed to identify additional association signals on chromosome
      1q22. In a separate cohort of healthy individuals with and without BEN, whole
      genome gene expression from peripheral blood neutrophils were analyzed for DARC.
      RESULTS: We confirmed that rs2814778 in DARC was associated with BEN (p = 4.09*10
      53). Conditioning on rs2814778 abolished other significant chromosome 1
      associations. Inflammatory cytokines (IL-2, 6, and 10) in participants in the
      Howard University Family Study (HUFS) and Multi-Ethnic Study in Atherosclerosis
      (MESA) showed similar levels in individuals homozygous for the rs2814778 allele
      compared to others, indicating cytokine sink hypothesis played a minor role in
      leukocyte homeostasis. Gene expression in neutrophils of individuals with and
      without BEN was also similar except for low DARC expression in BEN, suggesting
      normal function. BEN neutrophils had slightly activated profiles in leukocyte
      migration and hematopoietic stem cell mobilization pathways (expression fold
      change <2). CONCLUSIONS: These results in humans support the notion of DARC null
      erythroid progenitors preferentially differentiating to myeloid cells, leading to
      activated DARC null neutrophils egressing from circulation to the spleen, and
      causing relative neutropenia. Collectively, these human data sufficiently
      explained the mechanism DARC null red cell phenotype causing BEN and further
      provided a biologic basis that BEN is clinically benign.

PMID- 29596499
TI  - Specific protein carbonylation in human breast cancer tissue compared to adjacent
      healthy epithelial tissue.
AB  - Protein carbonylation is an irreversible post-translational modification induced
      by severe oxidative stress. Reactive oxygen species (ROS) are constantly produced
      in cells and play important roles in both cancer progression and cancer
      suppression. ROS levels can be higher in tumor compared to surrounding healthy
      tissue but ROS-induced specific protein carbonylation and its unique role in
      cancer progression or suppression is poorly understood. In this study, we
      utilized previously validated ELISA and western blot methods to analyze the total
      and specific protein carbonylation in flash-frozen human breast cancer and
      matched adjacent healthy tissue to compare relative total, and specific protein
      carbonylation. Mass spectrometry, two-color western, and immunoprecipitation
      methods were used to identify and confirm the specifically carbonylated proteins
      in breast tumor tissue. Superoxide dismutase (SOD) activity was measured as an
      indicator of antioxidant activity, and LC3-II protein level was analyzed for
      autophagy by western blot. Findings were further confirmed using the immortalized
      MDA-MB-231 and MDA-MB-468 breast cancer and MCF-12A noncancerous human epithelial
      breast cell lines. Our results indicate that tumor tissue has greater total
      protein carbonylation, lower SOD1 and SOD2 protein levels, lower total SOD
      activity, and higher LC3-II levels compared to adjacent healthy tissue. We
      identified and confirmed three specific proteins of interest; filamin A, heat
      shock protein 90beta (HSP90beta), and bifunctional glutamate/proline-tRNA ligase
      (EPRS), that were selectively carbonylated in tumor tissue compared to matched
      adjacent healthy tissue. Correspondingly, compared to noncancerous MCF-12A
      epithelial cells, MDA-MB-231 cancer cells exhibited an increase in filamin A and
      EPRS protein carbonylation, decreased total SOD activity, and increased
      autophagy, but not increased HSP90beta protein carbonylation. Identification of
      selectively carbonylated proteins and defining their roles in cancer progression
      may promote the development of targeted therapeutic approaches toward mitigating
      oxidative damage of these proteins.

PMID- 29596500
TI  - Coupled ultradian growth and curvature oscillations during gravitropic movement
      in disturbed wheat coleoptiles.
AB  - To grow straight and upright, plants need to regulate actively their posture.
      Gravitropic movement, which occurs when plants modify their growth and curvature
      to orient their aerial organ against the force of gravity, is a major feature of
      this postural control. A recent model has shown that graviception and
      proprioception are sufficient to account for the gravitropic movement and
      subsequent organ posture demonstrated by a range of species. However, some
      plants, including wheat coleoptiles, exhibit a stronger regulation of posture
      than predicted by the model. Here, we performed an extensive kinematics study on
      wheat coleoptiles during a gravitropic perturbation (tilting) experiment in order
      to better understand this unexpectedly strong regulation. Close temporal
      observations of the data revealed that both perturbed and unperturbed coleoptiles
      showed oscillatory pulses of elongation and curvature variation that propagated
      from the apex to the base of their aerial organs. In perturbed coleoptiles, we
      discovered a non-trivial coupling between the oscillatory dynamics of curvature
      and elongation. The relationship between those oscillations and the postural
      control of the organ remains unclear, but indicates the presence of a mechanism
      that is capable of affecting the relationship between elongation rate,
      differential growth, and curvature.

PMID- 29596501
TI  - Are diverse societies less cohesive? Testing contact and mediated contact
      theories.
AB  - Previous research has demonstrated that there is a negative relationship between
      ethnic diversity in a local community and social cohesion. Often the way social
      cohesion is assessed, though, varies across studies and only some aspects of the
      construct are included (e.g., trust). The current research explores the
      relationship between diversity and social cohesion across a number of indicators
      of social cohesion including neighbourhood social capital, safety, belonging,
      generalized trust, and volunteering. Furthermore, social psychological theories
      concerning the role of positive contact and its impact on feelings of threat are
      investigated. Using a sample of 1070 third generation 'majority' Australians and
      structural equation modelling (SEM), findings suggest ethnic diversity is related
      to positive intergroup contact, and that contact showed beneficial impacts for
      some indicators of social cohesion both directly and indirectly through reducing
      perceived threat. When interethnic contact and perceived threat are included in
      the model there is no direct negative effect between diversity and social
      cohesion. The theoretical implications of these findings are outlined including
      the importance of facilitating opportunities for positive contact in diverse
      communities.

PMID- 29596502
TI  - Correction: Developmental finite element analysis of cichlid pharyngeal jaws:
      Quantifying the generation of a key innovation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189985.].

PMID- 29596503
TI  - Empirical radio propagation model for DTV applied to non-homogeneous paths and
      different climates using machine learning techniques.
AB  - The establishment and improvement of transmission systems rely on models that
      take into account, (among other factors), the geographical features of the
      region, as these can lead to signal degradation. This is particularly important
      in Brazil, where there is a great diversity of scenery and climates. This article
      proposes an outdoor empirical radio propagation model for Ultra High Frequency
      (UHF) band, that estimates received power values that can be applied to non
      homogeneous paths and different climates, this last being of an innovative
      character for the UHF band. Different artificial intelligence techniques were
      chosen on a theoretical and computational basis and made it possible to
      introduce, organize and describe quantitative and qualitative data quickly and
      efficiently, and thus determine the received power in a wide range of settings
      and climates. The proposed model was applied to a city in the Amazon region with
      heterogeneous paths, wooded urban areas and fractions of freshwater among other
      factors. Measurement campaigns were conducted to obtain data signals from two
      digital TV stations in the metropolitan area of the city of Belem, in the State
      of Para, to design, compare and validate the model. The results are consistent
      since the model shows a clear difference between the two seasons of the studied
      year and small RMS errors in all the cases studied.

PMID- 29596504
TI  - Influences of Native American land use on the Colonial Euro-American settlement
      of the South Carolina Piedmont.
AB  - We test the hypothesis that prehistoric Native American land use influenced the
      Euro-American settlement process in a South Carolina Piedmont landscape. Long
      term ecological studies demonstrate that land use legacies influence processes
      and trajectories in complex, coupled social and ecological systems. Native
      American land use likely altered the ecological and evolutionary feedback and
      trajectories of many North American landscapes. Yet, considerable debate revolves
      around the scale and extent of land use legacies of prehistoric Native Americans.
      At the core of this debate is the question of whether or not European colonists
      settled a mostly "wild" landscape or an already "humanized" landscape. We use
      statistical event analysis to model the effects of prehistoric Native American
      settlement on the rate of Colonial land grants (1749-1775). Our results reveal
      how abandoned Native American settlements were among the first areas claimed and
      homesteaded by Euro-Americans. We suggest that prehistoric land use legacies
      served as key focal nodes in the Colonial era settlement process. As a
      consequence, localized prehistoric land use legacies likely helped structure the
      long term, landscape- to regional-level ecological inheritances that resulted
      from Euro-American settlement.

PMID- 29596506
TI  - Correction: Chaos-Based Simultaneous Compression and Encryption for Hadoop.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0168207.].

PMID- 29596505
TI  - Childhood behavioral inhibition is associated with impaired mentalizing in
      adolescence.
AB  - Recent advances suggest that impairment in social cognition (SC) may play a role
      in the development of social anxiety (SA). However, very few studies have
      analyzed whether SA fosters poorer social-cognitive development as it leads to
      social avoidance. This study aimed to analyze whether retrospectively assessed
      behavioral inhibition (BI) (i.e., an early form of SA) in childhood is associated
      with a deficit in social cognition operationalized as impairment of mentalizing
      (MZ) in adolescence. A sample of 256 adolescents (range: 12-18 years; mean age:
      14.7 years; SD = 1.7) from general population were assessed for MZ capacities and
      retrospective BI through self-report and interview measures. Results comparing
      three groups of adolescents with different levels of childhood BI (low, moderate
      or high) and controlling for concurrent SA and depression reveal that the higher
      the level of BI, the lower the level of MZ. These results were consistent for
      almost all mentalization measures, including when both extreme (i.e., high vs.
      low BI) and non-extreme (i.e., high vs. moderate BI) were compared in both self
      report and interview measures and in both dimensions of MZ (i.e., MZ referred to
      others' and to own mental states). These findings support that childhood forms of
      SA are associated to deficit in SC in adolescence. A possible bi-directional
      relationship between SA and SC, and the role that it may play in the pathway to
      clinical SA are discussed.

PMID- 29596507
TI  - Comparison of the immune response during acute and chronic Staphylococcus aureus
      infection.
AB  - Staphylococcus aureus bacteria are able to grow in a planktonic state that is
      associated with acute infections and in biofilms that are associated with chronic
      infections. Acute infections, such as skin infections, are often self-limiting.
      However, chronic infections, such as implant infections, can be difficult to
      clear and may require surgical intervention. The host immune response may
      contribute to the different outcomes often associated with these two disease
      types. We used proteomic arrays and two murine models for an initial, descriptive
      characterization of the contribution of the host immune response to outcomes of
      acute versus chronic S. aureus disease. We compared the immune responses between
      a model of self-limiting skin and soft tissue infection caused by the planktonic
      form of S. aureus versus a model of surgical mesh implant infection, which we
      show to be caused by a bacterial biofilm. The significantly altered host
      cytokines and chemokines were largely different in the two models, with responses
      diminished by 21 days post-implantation in surgical mesh infection. Because
      bacterial levels remained constant during the 21 days that the surgical mesh
      infection was followed, those cytokines that are significantly increased during
      chronic infection are not likely effective in eradicating biofilm. Comparison of
      the levels of cytokines and chemokines in acute versus chronic S. aureus
      infection can provide a starting point for evaluation of the role of specific
      immune factors that are present in one disease manifestation but not the other.

PMID- 29596508
TI  - Pearls collections: What we can learn about infectious disease and cancer.

PMID- 29596509
TI  - Quantitative patterns of vertical transmission of deformed wing virus in honey
      bees.
AB  - Deformed wing virus (DWV) is an important pathogen in a broad range of insects,
      including honey bees. Concordant with the spread of Varroa, DWV is present in the
      majority of honey bee colonies and can result in either low-level infections with
      asymptomatic bees that nonetheless exhibit increased colony loss under stress, or
      high-level infections with acute effects on bee health and viability. DWV can be
      transmitted vertically or horizontally and evidence suggests that horizontal
      transmission via Varroa is associated with acute symptomatic infections. Vertical
      transmission also occurs and is presumably important for the maintenance of DWV
      in honey bee populations. To further our understanding the vertical transmission
      of DWV through queens, we performed three experiments: we studied the
      quantitative effectiveness of vertical transmission, surveyed the prevalence of
      successful egg infection under commercial conditions, and distinguished among
      three possible mechanisms of transmission. We find that queen-infection level
      predicts the DWV titers in their eggs, although the transmission is not very
      efficient. Our quantitative assessment of DWV demonstrates that eggs in 1/3 of
      the colonies are infected with DWV and highly infected eggs are rare in newly
      installed spring colonies. Additionally, our results indicate that DWV
      transmission occurs predominantly by virus adhering to the surface of eggs
      (transovum) rather than intracellularly. Our combined results suggest that the
      queens' DWV vectoring capacity in practice is not as high as its theoretical
      potential. Thus, DWV transmission by honey bee queens is part of the DWV epidemic
      with relevant practical implications, which should be further studied.

PMID- 29596511
TI  - Correction: Fuzzy-based propagation of prior knowledge to improve large-scale
      image analysis pipelines.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187535.].

PMID- 29596510
TI  - Correction: SubID, a non-median dichotomization tool for heterogeneous
      populations, reveals the pan-cancer significance of INPP4B and its regulation by
      EVI1 in AML.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191510.].

PMID- 29596512
TI  - The composition of polypharmacy: A register-based study of Swedes aged 75 years
      and older.
AB  - BACKGROUND: Polypharmacy is common among older adults. However, little is known
      about the composition of polypharmacy: which are the most frequently used drugs,
      and how much do these drugs contribute to the overall prevalence of polypharmacy.
      METHODS: A total of 822,619 Swedes aged >=75 years was identified from the Total
      Population Register. Through record-linkage with the Swedish Prescribed Drug
      Register and the Social Services Register we could analyze concurrent drug use in
      the entire population (both individuals living in the community and institution)
      on the 31 December 2013. RESULTS: The prevalence of polypharmacy (>=5 drugs) was
      45%. The most frequently used drugs were cardiovascular drugs, analgesics, and
      psychotropics. By excluding the ten most frequently used drug classes or
      compounds, the prevalence of polypharmacy was reduced by 69% and 51%
      respectively. The majority of the users of either one of the 10 most frequently
      used drugs concurrently used at least 4 other drug classes (66%-85%). CONCLUSION:
      Almost half of the individuals aged >=75 years are exposed to polypharmacy in
      Sweden. A handful of drugs make a large contribution to the overall prevalence of
      polypharmacy and the majority of drugs prescribed to persons aged >=75 years are
      used in combination with other drugs. This highlights the high use of drugs, and
      the need to consider other concurrent drug treatments when prescribing for older
      adults.

PMID- 29596513
TI  - Bad manners in the Emergency Department: Incivility among doctors.
AB  - INTRODUCTION: Negative workplace behaviour, especially negative communication is
      a recognised problem in many organisations and is known to have serious impact on
      workplace performance, productivity and personal wellbeing. Emergency Departments
      (ED) can be high stress environments in which communication and perceptions of
      respect between physicians and other staff may underlie individual functioning.
      We conducted a study to estimate the influence of incivility (ICV) among
      physicians in the ED. METHODS: We developed an online survey to assess workplace
      incivility in the ED. We focussed on frequency, origin, reasons and situations
      where ICV was reported. To measure the levels and the potential influence of ICV
      on psychological safety, social stress and personal wellbeing we correlated our
      questionnaire to standard psychological scales. Statistical analysis included
      Students t-test, chi squared distribution and Pearson correlation coefficient.
      RESULTS: We invited all seventy-seven ED physicians to participate in our survey.
      Among those that completed (n = 50, 65%) the survey, 9% of ED physicians reported
      frequent (1/week) and 38% occasional (1/month) incidents of ICV. 28% of
      physicians reported experiencing ICV once per quarter and 21% reported a
      frequency of only once per year, no physician reported ICV on a daily basis.
      Levels of ICV were significantly higher in interactions with specialists from
      outside then within the ED (p<0.01). ICV was perceived particularly during
      critical situations. Our findings showed a significant correlation between
      internal (within the ED team) ICV and psychological safety. To ED physicians
      internal ICV was associated with lower levels of psychological safety (p<0.01).
      ICV displayed from sources outside the ED team was not associated with
      psychological safety, but we found a significant influence of external ICV on
      personal irritability and reduced wellbeing (p<0.01). DISCUSSION: The incidence
      of incivility was high among the ED physicians. Although this was a small sample,
      the association between workplace ICV and psychological safety, personal
      irritation as well personal comfort suggests that ICV may be an important
      variable underlying ED team performance. These findings further underscore the
      need to foster a culture of respect and good communication between departments,
      as levels of ICV were highest with physicians from outside the ED. Future
      research would benefit from examining strategies to prevent and reduce ICV and
      identify reasons for personal variation in perception of ICV. During critical
      situations and in general collaboration with specialists, awareness of ICV and
      countermeasures are important to avoid decreased performance and negative impact
      on staff and patient.

PMID- 29596514
TI  - Characterisation of insulin analogues therapeutically available to patients.
AB  - The structure and function of clinical dosage insulin and its analogues were
      assessed. This included 'native insulins' (human recombinant, bovine, porcine),
      'fast-acting analogues' (aspart, glulisine, lispro) and 'slow-acting analogues'
      (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation
      velocity and equilibrium experiments, were employed to yield distributions of
      both molar mass and sedimentation coefficient of all nine insulins. Size
      exclusion chromatography, coupled to multi-angle light scattering, was also used
      to explore the function of these analogues. On ultracentrifugation analysis, the
      insulins under investigation were found to be in numerous conformational states,
      however the majority of insulins were present in a primarily hexameric
      conformation. This was true for all native insulins and two fast-acting
      analogues. However, glargine was present as a dimer, detemir was a multi
      hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present
      as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography
      showed that the two hexameric fast-acting analogues (aspart and lispro)
      dissociated into monomers and dimers due to the lack of zinc in the mobile phase.
      This comprehensive study is the first time all nine insulins have been
      characterised in this way, the first time that insulin detemir have been studied
      using analytical ultracentrifugation and the first time that insulins aspart and
      glulisine have been studied using sedimentation equilibrium. The structure and
      function of these clinically administered insulins is of critical importance and
      this research adds novel data to an otherwise complex functional physiological
      protein.

PMID- 29596515
TI  - Primary care pediatricians' attitudes and practice towards HPV vaccination: A
      nationwide survey in Italy.
AB  - This national online cross-sectional survey in Italy assessed primary care
      pediatricians' (PCPs) attitudes and practices regarding Human papillomavirus
      (HPV) vaccination and the contribution of several characteristics. The
      questionnaire was distributed from September 2016 to June 2017 to a random sample
      of 640 PCPs by email via an internet-link leading to a web-based survey platform
      (Lime Survey). Only 18.4% of PCPs always recommend the HPV vaccine to 11-12 year
      old boys. PCPs with longer practice activity, working in solo practice, always
      recommended the HPV vaccine to 11-12 year old girls, and believed that the
      vaccine was effective for boys were more likely to always recommend the HPV
      vaccine. PCPs working in a Region where the vaccination was actively recommended
      and provided free of charge to 11-12 year old boys had higher odds of
      recommending vaccination. More than two thirds of PCPs (77.4%) always recommend
      the HPV vaccine to 11-12 year old girls. PCPs who believed that the vaccine was
      effective for girls and safe in both boys and girls, who always talk with
      patients of 11-18 years or their parents about HPV infection and vaccination, and
      who obtain vaccine information from scientific journals were more likely to
      always recommend the vaccine. PCPs should employ evidence-based educational
      strategies in order to achieve a better coverage and to reduce the morbidities
      and mortality of diseases associated with HPV.

PMID- 29596516
TI  - Age-specific characterization of spinal cord injuries over a 19-year period at a
      Japanese rehabilitation center.
AB  - Regional demographics of spinal cord injuries (SCIs) are fundamental to
      identifying and implementing appropriate preventive measures. The current study
      was conducted as a longitudinal analysis of all patients with SCIs admitted to
      the Hyogo Rehabilitation Center over a 19-year period. The sex and age of the
      patient, time and nature of injury (i.e., cause, level, and extent), and period
      from injury to admission were evaluated retrospectively. Pertinent tests,
      including Poisson regression analysis, and the Cochran-Armitage, Kruskal-Wallis,
      and chi-square tests, were applied to assess demographic variables, with
      statistical significance set at p < 0.05. Between 1995 and 2013, a total of 632
      patients with SCIs (predominantly male and largely < 60 years old) were admitted
      to our center for rehabilitation. Although the male: female ratio remained
      unchanged throughout the study period, the ratio of older adults increased over
      time. In assessing the cause of injury, the majority of the patients involved in
      road traffic accidents were aged <= 44 years, whereas patients aged >= 45 years
      accounted for the majority of low-distance falls and disease-related SCIs, the
      proportions of which gradually increased. Complete paralysis and paraplegia
      primarily occurred in patients aged <= 44 years, whereas the majority of
      incomplete injuries and tetraplegia were limited to those aged >= 45 years. The
      patient age at the time of SCI and the nature of the injury sustained were
      interrelated. Age-specific strategies thus offered the best means of
      preventing/reducing the incidence of SCIs in Hyogo prefecture.

PMID- 29596517
TI  - Does farmer entrepreneurship alleviate rural poverty in China? Evidence from
      Guangxi Province.
AB  - In recent years, entrepreneurship has been gaining more prominence as a potential
      tool for solving poverty in developing countries. This paper mainly examines the
      relationship between farmer entrepreneurship and rural poverty alleviation in
      China by assessing the contribution of farm entrepreneurs towards overcoming
      poverty. Data were collected from 309 employees of farmer entrepreneurships in
      Guangxi Province through survey questionnaires. Structural equation modeling was
      used to conduct an analysis of the effects of three identified capabilities of
      farm entrepreneurs-economic, educational and knowledge, and socio-cultural
      capabilities-on attitude towards farmer entrepreneurship growth and the
      qualitative growth of farmer entrepreneurship and how these in turn affect rural
      poverty, using AMOS 21. The findings show that socio-cultural capability has the
      greatest influence on farmer entrepreneurship growth (beta = 0.50, p<0.001). The
      qualitative growth of farmer entrepreneurship also more significantly impacts
      rural poverty (beta = 0.69, p<0.001) than attitude towards farmer
      entrepreneurship growth. This study suggests that policy makers in China should
      involve more rural farmers in the targeted poverty alleviation strategies of the
      government by equipping rural farmers with entrepreneurial skills. This can serve
      as a sustainable, bottom-up approach to alleviating rural poverty in remote areas
      of the country. The study also extends the literature on the farmer
      entrepreneurship-rural poverty alleviation nexus in China, and this can serve as
      a lesson for other developing countries in the fight against rural poverty.

PMID- 29596518
TI  - All-optical recording and stimulation of retinal neurons in vivo in retinal
      degeneration mice.
AB  - Here we demonstrate the application of a method that could accelerate the
      development of novel therapies by allowing direct and repeatable visualization of
      cellular function in the living eye, to study loss of vision in animal models of
      retinal disease, as well as evaluate the time course of retinal function
      following therapeutic intervention. We use high-resolution adaptive optics
      scanning light ophthalmoscopy to image fluorescence from the calcium sensor
      GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored
      visual responses in ganglion cell layer neurons expressing the red-shifted
      channelrhodopsin ChrimsonR over a six-week period following significant loss of
      visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and
      adaptive optics enables all-optical stimulation and recording of retinal neurons
      in the living eye. Because the retina is an accessible portal to the central
      nervous system, our method also provides a novel non-invasive method of
      dissecting neuronal processing in the brain.

PMID- 29596519
TI  - Response of human normal and leukemia cells to factors released by amnion
      fragments in vitro.
AB  - Amnion is a membrane surrounding the embryo/fetus which determine growth factors
      and interleukins with angiogenic, immunogenic, and anti-inflammatory properties.
      The aim of the present study was to investigate the effects of conditioned
      culture medium from 24-h cultures of human amnion (hAM CCM) on migration and
      proliferation of human umbilical vein endothelial primary cells (HUVECs), freshly
      isolated bone marrow mononuclear cells (BM MNCs), and Jurkat leukemia cell line.
      Amnion membrane was freshly isolated from healthy placenta and its fragments
      cultured in vitro to produce hAM CCM. Members of the IGFBP protein family made up
      one third of all assayed proteins present in the hAM medium. The hAM CCM did not
      affect the proliferation rate of HUVECs or MNCs, but we observed more intensive
      migration of those cells, and lower expression of CD31 surface antigen on HUVECs
      as compared to control cultures. In contrast, Jurkat cells did not respond to hAM
      CCM treatment by proliferation or mobility change. The conditioned medium from 24
      h cultures of human amnion is easy to obtain and is a convenient source of
      various growth and other factors that may be useful in practical medicine.

PMID- 29596520
TI  - Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by
      suppressing mammalian Diaphanous-related formin-2 (mDia2).
AB  - The tumor microenvironment (TME) promotes tumor cell invasion and metastasis. An
      important step in the shift to a pro-cancerous microenvironment is the
      transformation of normal stromal fibroblasts to carcinoma-associated fibroblasts
      (CAFs). CAFs are present in a majority of solid tumors and can directly promote
      tumor cell motility via cytokine, chemokine and growth factor secretion into the
      TME. The exact effects that the TME has upon cytoskeletal regulation in motile
      tumor cells remain enigmatic. The conserved formin family of cytoskeleton
      regulating proteins plays an essential role in the assembly and/or bundling of
      unbranched actin filaments. Mammalian Diaphanous-related formin 2
      (mDia2/DIAPH3/Drf3/Dia) assembles a dynamic F-actin cytoskeleton that underlies
      tumor cell migration and invasion. We therefore sought to understand whether CAF
      derived chemokines impact breast tumor cell motility through modification of the
      formin-assembled F-actin cytoskeleton. In MDA-MB-231 cells, conditioned media
      (CM) from WS19T CAFs, a human breast tumor-adjacent CAF line, significantly and
      robustly increased wound closure and invasion relative to normal human mammary
      fibroblast (HMF)-CM. WS19T-CM also promoted proteasome-mediated mDia2 degradation
      in MDA-MB-231 cells relative to control HMF-CM and WS21T CAF-CM, a breast CAF
      cell line that failed to promote robust MDA-MB-231 migration. Cytokine array
      analysis of CM identified up-regulated secreted factors in WS19T relative to
      control WS21T CM. We identified CXCL12 as a CM factor influencing loss of mDia2
      protein while increasing MDA-MB-231 cell migration. Our data suggest a mechanism
      whereby CAFs promote tumor cell migration and invasion through CXCL12 secretion
      to regulate the mDia2-directed cytoskeleton in breast tumor cells.

PMID- 29596521
TI  - Fear of falling in community-dwelling older adults: A cause of falls, a
      consequence, or both?
AB  - BACKGROUND: Despite the number of studies that have tried to demonstrate that
      there is an association between previous falls and the fear of falling, the
      relationship between these two variables remains a matter of controversy.
      OBJECTIVES: Our objective was to investigate whether the fear of falling is a
      cause of falls, a consequence, or both in community-dwelling adults aged >= 75
      years old. METHODS: A descriptive, longitudinal, prospective study was performed.
      A total of 640 individuals were interviewed between 2009 and 2011.
      Sociodemographic data, health status, history of falls and fear of falling were
      assessed at baseline and at 24 months. RESULTS: The prevalence of falls at
      baseline was 25% as opposed to 35.2% at 24 months. The prevalence of the fear of
      falling was 41.5% at baseline. Logistic regression analysis showed a significant
      association between a history of falls and the fear of falling. Other factors
      associated with the fear of falling were female gender, comorbidity, depressive
      symptoms, and disability. In total, 41.7% of the subjects who had reported a fear
      of falling at baseline had suffered at least one fall 24 months later. Unadjusted
      Cox regression analysis revealed that the fear of falling was a risk factor for
      falls. According to the final model adjusted for other covariates, the only
      reliable predictor was female gender. The Cox model stratified by gender failed
      to show a crude association between fear of falling and falls. CONCLUSION: A
      previous history of falls in the previous year was a good predictor of the fear
      of falling; but the fear of falling was a predictor of falls during follow-up
      only in the unadjusted model, pointing to strong gender turns out as an effect
      modifier of the association of FOF and subsequent falls. Nursing staff working in
      elderly care should not only routinely assess patients' previous history of
      falls, but also evaluate their fear of falling and its associated factors.

PMID- 29596522
TI  - Could texture features from preoperative CT image be used for predicting occult
      peritoneal carcinomatosis in patients with advanced gastric cancer?
AB  - PURPOSE: To retrospectively investigate whether texture features obtained from
      preoperative CT images of advanced gastric cancer (AGC) patients could be used
      for the prediction of occult peritoneal carcinomatosis (PC) detected during
      operation. MATERIALS AND METHODS: 51 AGC patients with occult PC detected during
      operation from January 2009 to December 2012 were included as occult PC group.
      For the control group, other 51 AGC patients without evidence of distant
      metastasis including PC, and whose clinical T and N stage could be matched to
      those of the patients of the occult PC group, were selected from the period of
      January 2011 to July 2012. Each group was divided into test (n = 41) and
      validation cohort (n = 10). Demographic and clinical data of these patients were
      acquired from the hospital database. Texture features including average, standard
      deviation, kurtosis, skewness, entropy, correlation, and contrast were obtained
      from manually drawn region of interest (ROI) over the omentum on the axial CT
      image showing the omentum at its largest cross sectional area. After using
      Fisher's exact and Wilcoxon signed-rank test for comparison of the clinical and
      texture features between the two groups of the test cohort, conditional logistic
      regression analysis was performed to determine significant independent predictor
      for occult PC. Using the optimal cut-off value from receiver operating
      characteristic (ROC) analysis for the significant variables, diagnostic
      sensitivity and specificity were determined in the test cohort. The cut-off value
      of the significant variables obtained from the test cohort was then applied to
      the validation cohort. Bonferroni correction was used to adjust P value for
      multiple comparisons. RESULTS: Between the two groups, there was no significant
      difference in the clinical features. Regarding the texture features, the occult
      PC group showed significantly higher average, entropy, standard deviation, and
      significantly lower correlation (P value < 0.004 for all). Conditional logistic
      regression analysis demonstrated that entropy was significant independent
      predictor for occult PC. When the cut-off value of entropy (> 7.141) was applied
      to the validation cohort, sensitivity and specificity for the prediction of
      occult PC were 80% and 90%, respectively. CONCLUSION: For AGC patients whose PC
      cannot be detected with routine imaging such as CT, texture analysis may be a
      useful adjunct for the prediction of occult PC.

PMID- 29596523
TI  - Autistic traits and social anxiety predict differential performance on social
      cognitive tasks in typically developing young adults.
AB  - The current work examined the unique contribution that autistic traits and social
      anxiety have on tasks examining attention and emotion processing. In Study 1, 119
      typically-developing college students completed a flanker task assessing the
      control of attention to target faces and away from distracting faces during
      emotion identification. In Study 2, 208 typically-developing college students
      performed a visual search task which required identification of whether a series
      of 8 or 16 emotional faces depicted the same or different emotions. Participants
      with more self-reported autistic traits performed more slowly on the flanker task
      in Study 1 than those with fewer autistic traits when stimuli depicted complex
      emotions. In Study 2, participants higher in social anxiety performed less
      accurately on trials showing all complex faces; participants with autistic traits
      showed no differences. These studies suggest that traits related to autism and to
      social anxiety differentially impact social cognitive processing.

PMID- 29596525
TI  - Correction: HMP-1/alpha-catenin promotes junctional mechanical integrity during
      morphogenesis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193279.].

PMID- 29596524
TI  - Effects of repetitive transcranial magnetic stimulation and trans-spinal direct
      current stimulation associated with treadmill exercise in spinal cord and
      cortical excitability of healthy subjects: A triple-blind, randomized and sham
      controlled study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans
      spinal direct current stimulation (tsDCS) modulate corticospinal circuits in
      healthy and injured subjects. However, their associated effects with physical
      exercise is still not defined. This study aimed to investigate the effect of
      three different settings of rTMS and tsDCS combined with treadmill exercise on
      spinal cord and cortical excitability of healthy subjects. We performed a triple
      blind, randomized, sham-controlled crossover study with 12 healthy volunteers who
      underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal,
      cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical
      excitability was assessed by motor evoked potential (MEP) and spinal cord
      excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and
      homosynaptic depression (HD). All measures were assessed before, immediately, 30
      and 60 minutes after the experimental procedures. Our results demonstrated that
      anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared
      to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's
      area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to
      sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise
      reduced Hr amplitude up to 30 minutes after stimulation offset and no changes
      were observed in HD measures. We demonstrated that tsDCS and rTMS combined with
      treadmill exercise modulated cortical and spinal cord excitability through
      different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way
      acting at local spinal circuits while rTMS probably promoted changes in the
      presynaptic inhibition of spinal motoneurons. In addition, the association of two
      neuromodulatory techniques induced long-lasting changes.

PMID- 29596526
TI  - ABO blood groups as a prognostic factor for recurrence in ovarian and vulvar
      cancer.
AB  - The relationship between ABO blood groups (BG) and risk of incidence in cancers
      including gynecological cancers has been widely studied, showing increased
      incidence risk for BG A patients. As available data are inconsistent we
      investigated whether BG and their anti-glycan antibodies (anti-A and anti-B) have
      prognostic values in gynecological cancers. We retrospectively evaluated 974
      patients with gynecological cancers in three cancer centers (Switzerland and
      Australia) between 1974 and 2014 regarding the relationships between clinico
      pathological findings and the BG. Time to disease recurrence was significantly
      influenced by BG in patients with ovarian (n = 282) and vulvar (n = 67) cancer.
      BG O or B patients showed a significantly increased risk for ovarian cancer
      relapse compared to A, 59% and 82%, respectively (p = 0.045; HR O vs A = 1.59 (CI
      1.01-2.51) and (p = 0.036; HR A vs B = 0.55 (CI 0.32-0.96). Median time to
      relapse for advanced stage (n = 126) ovarian cancer patients was 18.2 months for
      BG O and 32.2 for A (p = 0.031; HR O vs A = 2.07 (CI 1.07-4.02)). BG also
      significantly influenced relapse-free survival in patients with vulvar cancer (p
      = 0.002), with BG O tending to have increased relapse risk compared to A (p =
      0.089). Blood groups hence associate with recurrence in ovarian and vulvar
      cancer: women with BG O seem to have a lower ovarian cancer incidence, however
      are more likely to relapse earlier. The significance of the BG status as a
      prognostic value is evident and may be helpful to oncologists in prognosticating
      disease outcome and selecting the appropriate therapy.

PMID- 29596527
TI  - Influenza virus: 16 years' experience of clinical epidemiologic patterns and
      associated infection factors in hospitalized children in Argentina.
AB  - BACKGROUND: Influenza is an important cause of acute lower respiratory tract
      infection (aLRTI), hospitalization, and mortality in children. This study aimed
      to describe the clinical and epidemiologic patterns and infection factors
      associated with influenza, and compare case features of influenza A and B.
      METHODS: In a prospective, cross-sectional study, patients admitted for aLRTI,
      between 2000 and 2015, were tested for respiratory syncytial virus, adenovirus,
      influenza, or parainfluenza, and confirmed by fluorescent antibody (FA) or real
      time polymerase chain reaction (RT-PCR) assay of nasopharyngeal aspirates.
      RESULTS: Of 14,044 patients, 37.7% (5290) had FA- or RT-PCR-confirmed samples
      that identified influenza in 2.8% (394/14,044; 91.4% [360] influenza A, 8.6% [34]
      influenza B) of cases. Influenza frequency followed a seasonal epidemic pattern
      (May-July, the lowest average temperature months). The median age of cases was 12
      months (interquartile range: 6-21 months); 56.1% (221/394) of cases were male.
      Consolidated pneumonia was the most frequent clinical presentation (56.9%;
      224/394). Roughly half (49.7%; 196/394) of all cases had previous respiratory
      admissions; 9.4% (37/394) were re-admissions; 61.5% (241/392) had comorbidities;
      26.2% (102/389) had complications; 7.8% (30/384) had nosocomial infections. The
      average case fatality rate was 2.1% (8/389). Chronic neurologic disease was
      significantly higher in influenza B cases compared to influenza A cases (p =
      0.030). The independent predictors for influenza were: age >=6 months, odds ratio
      (OR): 1.88 (95% confidence interval [CI]: 1.44-2.45); p<0.001; presence of
      chronic neurologic disease, OR: 1.48 (95% CI: 1.01-2.17); p = 0.041; previous
      respiratory admissions, OR: 1.71 (95% CI: 1.36-2.14); p<0.001; re-admissions, OR:
      1.71 (95% CI: 1.17-2.51); p = 0.006; clinical pneumonia, OR: 1.50 (95% CI: 1.21
      1.87); p<0.001; immunodeficiency, OR: 1.87 (95% CI: 1.15-3.05); p = 0.011; cystic
      fibrosis, OR: 4.42 (95% CI: 1.29-15.14); p = 0.018. CONCLUSION: Influenza showed
      an epidemic seasonal pattern (May-July), with higher risk in children >=6 months,
      or with pneumonia, previous respiratory admissions, or certain comorbidities.

PMID- 29596528
TI  - Apaf1 plays a negative regulatory role in T cell responses by suppressing
      activation of antigen-stimulated T cells.
AB  - Apaf1 is a critical component of the apoptosome and initiates apoptosis
      downstream mitochondrial damages. Although the importance of Apaf1 in embryonic
      development was shown, the role of Apaf1 in immune responses, especially T cell
      responses, has yet to be elucidated. We generated T cell-specific Apaf1-deficient
      mice (Lck-Cre-Apaf1f/f mice) and examined the antigen-specific delayed-type
      hypersensitivity (DTH). Lck-Cre-Apaf1f/f mice exhibited exacerbation of DTH
      responses as compared with Apaf1-sufficient control mice. In Lck-Cre-Apaf1f/f
      mice, antigen-specific T cells proliferated more, and produced more inflammatory
      cytokines than control T cells. Apaf1-deficient T cells from antigen-immunized
      mice showed higher percentages of activation phenotypes upon restimulation in
      vitro. Apaf1-deficient T cells from naive (non-immunized) mice also showed higher
      proliferation activity and cytokine production over control cells. The impact of
      Apaf1-deficiency in T cells, however, was not restored by a pan-caspase
      inhibitor, suggesting that the role of Apaf1 in T cell responses was caspase
      independent/non-apoptotic. These data collectively demonstrated that Apaf1 is a
      negative regulator of T cell responses and implicated Apaf1 as a potential target
      for immunosuppressive drug discovery.

PMID- 29596530
TI  - Establishment and characterization of pygmy killer whale (Feresa attenuata)
      dermal fibroblast cell line.
AB  - The pygmy killer whale (Feresa attenuata) (PKW) is a tropical and subtropical
      marine mammal commonly found in the Atlantic, Indian and Pacific oceans. Since
      the PKWs live in offshore protected territories, they are rarely seen onshore.
      Hence, PKW are one of the most poorly understood oceanic species of odontocetes.
      The dermal tissue comes primarily from stranding events that occur along the
      coast of the Shantou, Guangdong, China. The sampled tissues were immediately
      processed and attached on collagen-coated 6-well tissue culture plate. The
      complete medium (DMEM and Ham's F12, fetal bovine serum, antibiotic and essential
      amino acids) was added to the culture plates. The primary culture (PKW-LWH) cells
      were verified as fibroblast by vimentin and karyotype analyses, which revealed 42
      autosomes and two sex chromosomes X and Y. Following transfection of PKW-LWH
      cells with a plasmid encoding, the SV40 large T-antigens and the transfected
      cells were isolated and expanded. Using RT-PCR, western blot, immunofluorescence
      analysis and SV40 large T-antigen stability was confirmed. The cell proliferation
      rate of the fibroblast cells, PKW-LWHT was faster than the primary cells PKW-LWH
      with the doubling time 68.9h and 14.4h, respectively. In this study, we
      established PKW dermal fibroblast cell line for the first time, providing a
      unique opportunity for in vitro studies on the effects of environmental
      pollutants and pathogens that could be determined in PKW and/or Cetaceans.

PMID- 29596529
TI  - Genome-wide identification of wheat (Triticum aestivum) expansins and expansin
      expression analysis in cold-tolerant and cold-sensitive wheat cultivars.
AB  - Plant expansins are proteins involved in cell wall loosening, plant growth, and
      development, as well as in response to plant diseases and other stresses. In this
      study, we identified 128 expansin coding sequences from the wheat (Triticum
      aestivum) genome. These sequences belong to 45 homoeologous copies of TaEXPs,
      including 26 TaEXPAs, 15 TaEXPBs and four TaEXLAs. No TaEXLB was identified. Gene
      expression and sub-expression profiles revealed that most of the TaEXPs were
      expressed either only in root tissues or in multiple organs. Real-time qPCR
      analysis showed that many TaEXPs were differentially expressed in four different
      tissues of the two wheat cultivars-the cold-sensitive 'Chinese Spring (CS)' and
      the cold-tolerant 'Dongnongdongmai 1 (D1)' cultivars. Our results suggest that
      the differential expression of TaEXPs could be related to low-temperature
      tolerance or sensitivity of different wheat cultivars. Our study expands our
      knowledge on wheat expansins and sheds new light on the functions of expansins in
      plant development and stress response.

PMID- 29596532
TI  - Intention to quit and the role of dark personality and perceived organizational
      support: A moderation and mediation model.
AB  - This study investigated the role of individual differences (dark personality) and
      situational factors (perceived organisational support) in explaining intention to
      quit. Four hundred and fifty-one (50 of which females) ambulance personnel
      completed three questionnaires (Hogan Development Survey; Perceived
      Organisational Support Survey; and a single item Intention to Quit measure) as a
      part of a selection and development assessment. Employees high on Excitable,
      Sceptical, and Mischievous, but low on Colourful were found to have greater
      intentions to quit. Additionally, employees high on Excitable, Sceptical,
      Reserved, and Leisurely, but low on Dutiful and Diligent had lower perceptions of
      organisational support. Structural Equation Modelling revealed that perceived
      organisational support plays both a mediating and moderating role on dark
      personality and intention to quit. Theoretical implications of personality's role
      in perceived organisational support and intention to quit are discussed.

PMID- 29596531
TI  - Insights into DNA substrate selection by APOBEC3G from structural, biochemical,
      and functional studies.
AB  - Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3)
      proteins are a family of cytidine deaminases that catalyze the conversion of
      deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). A3
      proteins act in the innate immune response to viral infection by mutating the
      viral ssDNA. One of the most well-studied human A3 family members is A3G, which
      is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate
      sequence for catalysis-for example, A3G deaminates the third dC in the CCCA
      sequence motif. However, the interaction between A3G and ssDNA is difficult to
      characterize due to poor solution behavior of the full-length protein and loss of
      DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring
      fusion strategy using the protection of telomeres protein 1 (Pot1) which has
      nanomolar affinity for ssDNA, with which we captured an A3G-ssDNA interaction. We
      crystallized a non-preferred adenine in the -1 nucleotide-binding pocket of A3G.
      The structure reveals a unique conformation of the catalytic site loops that
      sheds light onto how the enzyme scans substrate in the -1 pocket. Furthermore,
      our biochemistry and virology studies provide evidence that the nucleotide
      binding pockets on A3G influence each other in selecting the preferred DNA
      substrate. Together, the results provide insights into the mechanism by which A3G
      selects and deaminates its preferred substrates and help define how A3 proteins
      are tailored to recognize specific DNA sequences. This knowledge contributes to a
      better understanding of the mechanism of DNA substrate selection by A3G, as well
      as A3G antiviral activity against HIV-1.

PMID- 29596533
TI  - Pluripotency gene network dynamics: System views from parametric analysis.
AB  - Multiple experimental data demonstrated that the core gene network orchestrating
      self-renewal and differentiation of mouse embryonic stem cells involves activity
      of Oct4, Sox2 and Nanog genes by means of a number of positive feedback loops
      among them. However, recent studies indicated that the architecture of the core
      gene network should also incorporate negative Nanog autoregulation and might not
      include positive feedbacks from Nanog to Oct4 and Sox2. Thorough parametric
      analysis of the mathematical model based on this revisited core regulatory
      circuit identified that there are substantial changes in model dynamics occurred
      depending on the strength of Oct4 and Sox2 activation and molecular complexity of
      Nanog autorepression. The analysis showed the existence of four dynamical domains
      with different numbers of stable and unstable steady states. We hypothesize that
      these domains can constitute the checkpoints in a developmental progression from
      naive to primed pluripotency and vice versa. During this transition, parametric
      conditions exist, which generate an oscillatory behavior of the system explaining
      heterogeneity in expression of pluripotent and differentiation factors in serum
      ESC cultures. Eventually, simulations showed that addition of positive feedbacks
      from Nanog to Oct4 and Sox2 leads mainly to increase of the parametric space for
      the naive ESC state, in which pluripotency factors are strongly expressed while
      differentiation ones are repressed.

PMID- 29596534
TI  - The characteristics of premature infants with transient corneal haze.
AB  - BACKGROUND: The etiology of transient corneal haze in premature infants is not
      known and how it relates to clinical outcomes in premature infants is not clear.
      OBJECTIVES: To study associated factors of transient corneal haze in premature
      infants. METHODS: We performed a retrospective study of 261 premature infants
      from retinopathy of prematurity (ROP) screening in the neonatal intensive care
      unit at a tertiary referral hospital. Characteristics of premature infants with
      and without corneal haze were analyzed by correlation tests, Chi-square tests,
      and logistic regressions were used for statistical analyses. Associations between
      corneal haze and birth weight (BW), gestational age at birth (GA), central
      corneal thickness, intraocular pressure, and other systemic and ophthalmic data
      were evaluated. RESULTS: The incidence of corneal haze was 13.4%. Lower BW, lower
      GA, packed red blood cells (RBC) transfusion, more days on oxygen, older maternal
      age, bronchopulmonary disease, and stage 3 ROP are associated with corneal haze.
      The severity of corneal haze decreased with infants' postmenstrual age.
      Multivariate logistic regression analyses revealed that BW and maternal age are
      the most important predictors of corneal haze. CONCLUSION: Low BW and older
      maternal age are the most important predictors of corneal haze in premature
      infants. Premature infants with corneal haze could carry more systemic and ocular
      morbidities. Hence they may require more clinical attention. Corneal haze is
      unlikely to hinder the treatment of ROP. However, it is possible that corneal
      haze could hinder the examination of ROP in some infants. If corneal haze does
      interfere with ROP screening, a closer, more conservative follow-up schedule with
      a senior ophthalmologist experienced in managing ROP is recommended.

PMID- 29596536
TI  - Correction: Correlative microscopy of the constituents of a dinosaur rib fossil
      and hosting mudstone: Implications on diagenesis and fossil preservation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186600.].

PMID- 29596535
TI  - Hostile intruder: Toxoplasma holds host organelles captive.

PMID- 29596537
TI  - Correction: A parallel spatiotemporal saliency and discriminative online learning
      method for visual target tracking in aerial videos.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192246.].

PMID- 29596538
TI  - Self-reported cheating among medical students: An alarming finding in a cross
      sectional study from Saudi Arabia.
AB  - Academic misconduct/dishonesty has become widespread behavior among many
      university students across the globe, and medical education is not an exception.
      Until recently, few efforts have been made to study the dishonest behavior in
      Middle-Eastern universities. This study examined the prevalence and predisposing
      factors of cheating among medical students in Saudi Arabia and suggests suitable
      preventive measures. A cross-sectional survey-based study was conducted at a
      government medical college during the 2014-2015 academic year. The response rate
      was 58.5% (421/720). The overall cheating behavior practiced by the participants
      was 29%, predominantly by male students. High GPA scoring students were the least
      likely to cheat. The participants living with their families were more likely to
      cheat compared to those who were living apart from their families. The reasons
      participants gave to justify their cheating behavior included getting better
      grades, passing the course, and lacking preparation while still recognizing that
      cheating is a 'mistake.' Overall, significant academic misconduct concerning
      cheating was found among the Saudi medical students; this misconduct is alarming
      in a reputable government institution. The implementation of strict punishments,
      requiring ethical courses and creating ethical awareness by exploiting the
      potential of Islamic religious belief might help to control this problem.

PMID- 29596540
TI  - Questions About a Clinical Trial Evaluating the Addition of Cetuximab to
      Definitive Chemoradiation Therapy With Paclitaxel and Cisplatin for Patients With
      Esophageal Cancer.

PMID- 29596539
TI  - The sociocultural effects on orthopedic surgeries in Taiwan.
AB  - Various sociocultural factors affect healthcare-seeking behaviors. In Taiwanese
      society, superstitions and lunar festivals play important roles in people's
      lives. We investigated the impact of "Ghost Month" (the 7th lunar month) and
      Chinese New Year (the 12th lunar month and the 1st lunar month of the following
      year) on the number of elective surgeries and emergent surgeries in Taiwan. The
      number of total knee replacement (TKR) surgeries and proximal femur fracture
      (PFF) surgeries in each lunar month from 2000 to 2011 were extracted from the
      Taiwan National Health Insurance Database, a computerized and population-based
      database. Patients were then sorted by location of residence or gender. The
      average number of TKR surgeries performed was significantly lower during the 1st,
      7th, and 12th lunar months in urban areas, whereas in rural areas this trend was
      only evident in the 7th and 12th lunar months. There was however, no significant
      difference in the average number of PFF surgeries in each lunar month except for
      an increase seen in the 1st lunar month in rural patients (p<0.05). When sorted
      by gender, the average number of TKR surgeries was significantly decreased in the
      7th and 12th lunar months in male patients, and decreased in the 1st, 7th, and
      12th lunar months in female patients. In contrast, there was no difference in the
      average numbers of PFF surgeries in the 7th and 12th lunar months either in male
      or female patients. We proposed that the timing of elective surgeries such as TKR
      might be influenced by Ghost Month and Chinese New Year; however, emergent PFF
      surgeries were not significantly influenced by sociocultural beliefs and taboos
      in Taiwan.

PMID- 29596541
TI  - Association of Cerebrospinal Fluid Biomarkers of Central Nervous System Injury
      With Neurocognitive and Brain Imaging Outcomes in Children Receiving Chemotherapy
      for Acute Lymphoblastic Leukemia.
AB  - Importance: Little is known about treatment-related neurotoxic mechanisms in
      children with acute lymphoblastic leukemia (ALL) treated with chemotherapy only.
      Objective: To examine concentration of cerebrospinal fluid (CSF) biomarkers of
      brain injury at ALL diagnosis and during cancer therapy and to evaluate
      associations with long-term neurocognitive and neuroimaging outcomes and relevant
      genetic polymorphisms. Design, Setting, and Participants: This prospective cohort
      study included 235 patients with ALL who received a chemotherapy-only protocol.
      Patients provided CSF samples after diagnosis and throughout treatment. At 5 or
      more years after the diagnosis, 138 (69.7%) of 198 eligible survivors
      participated in long-term follow-up assessments. Children were treated from June
      1, 2000, through October 31, 2010. Follow-up was completed on October 21, 2014,
      and data were analyzed from August 1, 2015, through September 30, 2016.
      Exposures: Plasma concentration of high-dose intravenous methotrexate sodium and
      number of triple intrathecal chemotherapy injections. Main Outcomes and Measures:
      The CSF samples were assayed at 5 points from diagnosis to reinduction for
      biomarkers of myelin degradation (myelin basic protein [MBP]), neuronal damage
      (nerve growth factor [NGF] and total and phosphorylated tau protein),
      astrogliosis (glial fibrillary acidic protein [GFAP]), and neuroinflammation
      (chitotriosidase). DNA was genotyped for polymorphisms in drug metabolism,
      oxidative stress, and neurodevelopment. Leukoencephalopathy was evaluated by
      brain imaging. At 5 or more years after the diagnosis, survivors completed
      neurocognitive testing and brain imaging of white matter integrity. Results:
      Among the 235 patients with CSF samples (120 boys [51.1%] and 115 girls [48.9%];
      mean [SD] age at diagnosis, 6.8 [4.7] years), MBP and GFAP levels were elevated
      at baseline and through consolidation. The number of intrathecal injections was
      positively correlated with NGF level increase at consolidation (r = 0.19; P =
      .005). Increases in GFAP (risk ratio [RR], 1.23; 95% CI, 1.09-1.40), MBP (RR,
      1.06; 95% CI, 1.01-1.11), and total tau (RR, 1.76; 95% CI, 1.11-2.78) levels were
      associated with a higher risk for leukoencephalopathy and higher apparent
      diffusion coefficient in frontal lobe white matter 5 years after diagnosis
      (standardized estimate, 0.05; P < .001). Increase in total tau at consolidation
      was associated with worse attention (omissions z score estimate, -0.20; P = .04).
      Conclusions and Relevance: Glial injury may be present at diagnosis of ALL.
      Neuronal injury was associated with intrathecal chemotherapy. The CSF biomarkers
      may be useful in identifying individuals at risk for worse neurologic outcomes,
      particularly those with genetic susceptibility to poor brain function.

PMID- 29596543
TI  - Questions About a Clinical Trial Evaluating the Addition of Cetuximab to
      Definitive Chemoradiation Therapy With Paclitaxel and Cisplatin for Patients With
      Esophageal Cancer.

PMID- 29596542
TI  - Assessment of Tumor Sequencing as a Replacement for Lynch Syndrome Screening and
      Current Molecular Tests for Patients With Colorectal Cancer.
AB  - Importance: Universal tumor screening for Lynch syndrome (LS) in colorectal
      cancer (CRC) is recommended and involves up to 6 sequential tests. Somatic gene
      testing is performed on stage IV CRCs for treatment determination. The diagnostic
      workup for patients with CRC could be simplified and improved using a single up
      front tumor next-generation sequencing test if it has higher sensitivity and
      specificity than the current screening protocol. Objective: To determine whether
      up-front tumor sequencing (TS) could replace the current multiple sequential test
      approach for universal tumor screening for LS. Design, Setting, and Participants:
      Tumor DNA from 419 consecutive CRC cases undergoing standard universal tumor
      screening and germline genetic testing when indicated as part of the multicenter,
      population-based Ohio Colorectal Cancer Prevention Initiative from October 2015
      through February 2016 (the prospective cohort) and 46 patients with CRC known to
      have LS due to a germline mutation in a mismatch repair gene from January 2013
      through September 2015 (the validation cohort) underwent blinded TS. Main
      Outcomes and Measures: Sensitivity of TS compared with microsatellite instability
      (MSI) testing and immunohistochemical (IHC) staining for the detection of LS.
      Results: In the 465 patients, mean age at diagnosis was 59.9 years (range, 20-96
      years), and 241 (51.8%) were female. Tumor sequencing identified all 46 known LS
      cases from the validation cohort and an additional 12 LS cases from the 419
      member prospective cohort. Testing with MSI or IHC, followed by BRAF p.V600E
      testing missed 5 and 6 cases of LS, respectively. Tumor sequencing alone had
      better sensitivity (100%; 95% CI, 93.8%-100%) than IHC plus BRAF (89.7%; 95% CI,
      78.8%-96.1%; P = .04) and MSI plus BRAF (91.4%; 95% CI, 81.0%-97.1%; P = .07).
      Tumor sequencing had equal specificity (95.3%; 95% CI, 92.6%-97.2%) to IHC plus
      BRAF (94.6%; 95% CI, 91.9%-96.6%; P > .99) and MSI plus BRAF (94.8%; 95% CI,
      92.2%-96.8%; P = .88). Tumor sequencing identified 284 cases with KRAS, NRAS, or
      BRAF mutations that could affect therapy for stage IV CRC, avoiding another test.
      Finally, TS identified 8 patients with germline DPYD mutations that confer
      toxicity to fluorouracil chemotherapy, which could also be useful for treatment
      selection. Conclusions and Relevance: Up-front TS in CRC is simpler and has
      superior sensitivity to current multitest approaches to LS screening, while
      simultaneously providing critical information for treatment selection.

PMID- 29596544
TI  - Concomitant Genetic Alterations With Response to Treatment and Epidermal Growth
      Factor Receptor Tyrosine Kinase Inhibitors in Patients With EGFR-Mutant Advanced
      Non-Small Cell Lung Cancer.

PMID- 29596545
TI  - Questions About a Clinical Trial Evaluating the Addition of Cetuximab to
      Definitive Chemoradiation Therapy With Paclitaxel and Cisplatin for Patients With
      Esophageal Cancer-Reply.

PMID- 29596546
TI  - Rituximab Maintenance Therapy After First-Line Induction Chemoimmunotherapy for
      Follicular Lymphoma.
AB  - Clinical Question: Is rituximab maintenance therapy after first-line induction
      chemoimmunotherapy for follicular lymphoma associated with improved outcomes?
      Bottom Line: Compared with observation, rituximab maintenance therapy prolongs
      progression-free survival without an improvement in overall survival or quality
      of life after first-line induction chemoimmunotherapy.

PMID- 29596548
TI  - Standardized Margin Assessment Is Needed Before Implementing Negative Margin as a
      Quality Measure-Reply.

PMID- 29596547
TI  - Targeted Intraoperative Radiation Therapy-A Promising Option for Accelerated
      Partial Breast Irradiation.

PMID- 29596549
TI  - Preoperative Facial Nerve Mapping to Plan and Guide Pediatric Facial Vascular
      Anomaly Resection.
AB  - Importance: Facial vascular anomalies are surgical challenges due to their
      vascularity and facial nerve distortion. To assist facial vascular anomaly
      surgical treatment, presurgical percutaneous facial nerve stimulation and
      recording of compound motor action potentials can be used to map the facial nerve
      branches. During surgery, the nerve map and continuous intraoperative motor end
      plate potential monitoring can be used to reduce nerve injury. Objective: To
      investigate if preoperative facial nerve mapping (FNM) is associated with
      intraoperative facial nerve injury risk and safe surgical approach options
      compared with standard nerve integrity monitoring (NIM). Design, Setting, and
      Participants: This investigation was a historically controlled study at a
      tertiary vascular anomaly center in Seattle, Washington. Participants were 92
      pediatric patients with facial vascular anomalies undergoing definitive anomaly
      surgery (from January 1, 1999, through January 1, 2015), with 2 years' follow-up.
      In retrospective review, a consecutive FNM patient cohort after 2005 (FNM group)
      was compared with a consecutive historical cohort (1999-2005) (NIM group). Main
      Outcomes and Measures: Postoperative facial nerve function and selected surgical
      approach. For NIM and FNM comparisons, statistical analysis calculated odds
      ratios of nerve injury and operative approach, and time-to-event methods analyzed
      operative time. Results: The NIM group had 31 patients (median age, 3.3 years
      [interquartile range, 2.2-11.4 years]; 20 [65%] male), and the FNM group had 61
      patients (median age, 4.4 years [interquartile range, 1.5-11.0 years]; 26 [43%]
      male). In both groups, lymphatic malformation resection was most common (19 of 31
      [61%] in the NIM group and 32 of 61 [52%] in the FNM group), and the median
      anomaly volumes were similar (52.4 mL; interquartile range, 12.8-183.3 mL in the
      NIM group and 65.4 mL; interquartile range, 18.8-180.2 mL in the FNM group).
      Weakness in the facial nerve branches at 2 years after surgery was more common in
      the NIM group (6 of 31 [19%]) compared with the FNM group (1 of 61 [2%])
      (percentage difference, 17%; 95% CI, 3%-32%). Anterograde facial nerve dissection
      was used more in the NIM group (27 of 31 [87%]) compared with the FNM group (28
      of 61 [46%]) (percentage difference, 41%; 95% CI, 24%-58%). Treatment with
      retrograde dissection without identification of the main trunk of the facial
      nerve was performed in 21 of 61 (34%) in the FNM group compared with 0 of 31 (0%)
      in the NIM group. Operative time was significantly shorter in the FNM group, and
      patients in the FNM group were more likely to complete surgery sooner (adjusted
      hazard ratio, 5.36; 95% CI, 2.00-14.36). Conclusions and Relevance: Facial nerve
      mapping before facial vascular anomaly surgery was associated with less
      intraoperative facial nerve injury and shorter operative time. Mapping enabled
      direct identification of individual intralesional and perilesional nerve
      branches, reducing the need for traditional anterograde facial nerve dissection,
      and allowed for safe removal of some lesions after partial nerve dissection
      through transoral or direct excision.

PMID- 29596550
TI  - Anterior Chamber Chemotherapy in Retinoblastoma-Necessary But Not Sufficient for
      Aqueous Seeding Control-Reply.

PMID- 29596551
TI  - Thyroidectomy Practice After Implementation of the 2015 American Thyroid
      Association Guidelines on Surgical Options for Patients With Well-Differentiated
      Thyroid Carcinoma.
AB  - Importance: The recommended extent of surgery for well-differentiated thyroid
      carcinoma has been modified considerably in the updated 2015 American Thyroid
      Association guidelines published in January 2016. To date, the changes in
      clinical practice after publication of these new guidelines have not been
      demonstrated. Objective: The aim of this study was to evaluate clinical practice
      changes associated with implementation of the updated guidelines on the surgical
      procedure rates of total thyroidectomy, thyroid lobectomy, and completion
      thyroidectomy at a single tertiary medical center. Design, Setting, and
      Participants: This is a retrospective cohort study of 169 patients at the
      Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Patients with
      pathologically proved, well-differentiated thyroid carcinoma who underwent
      surgery between January 1, 2013, and December 31, 2014, were compared with
      patients who underwent surgery from January 1 to December 31, 2016. A total of
      434 thyroidectomy procedures were performed during the study period, and 251 had
      pathologically proved, well-differentiated thyroid carcinoma. Patients with
      tumors larger than 4 cm, involved lymph nodes, or bilateral nodules were
      excluded. Main Outcomes and Measures: Primary outcomes were the rate of up-front
      total thyroidectomy vs lobectomy and the rates of completion thyroidectomy before
      and after the implementation of the new guidelines. Results: Of the 169 patients
      in the final analysis, 118 (69.8%) were included from 2013 to 2014 and 51 (30.2%)
      in 2016. The mean (SD) age for the entire cohort was 44 (13.8) years, and 129
      (76.3%) were women. Up-front total thyroidectomy was performed in 72 of 118
      patients (61.0%) prior to the 2015 American Thyroid Association guidelines and 16
      of 51 (31.4%) following their implementation (odds ratio, 0.29; 95% CI, 0.14
      0.59). The rate of completion thyroidectomy also significantly decreased between
      these periods (73.9% vs 20.0%; odds ratio, 0.09; 95% CI, 0.04-0.19). Conclusions
      and Relevance: The updated 2015 American Thyroid Association guidelines
      implementation was associated with a significant decrease in the rates of both up
      front total thyroidectomy and completion thyroidectomy. According to these
      findings, only 1 of 5 patients who undergoes thyroid lobectomy will require a
      completion procedure.

PMID- 29596552
TI  - Yield, Techniques, and Complications of Transvitreal and Transscleral Biopsies in
      Small Uveal Melanoma.
AB  - Importance: Intraoperative adequacy check of biopsy samples can lead to a higher
      biopsy yield rate, and subsequent genomic analysis can provide patients with
      valuable prognostic information. Objectives: To examine the yield rates for
      transscleral and transvitreal fine-needle aspiration biopsies of small uveal
      melanoma less than 3.6 mm in apical height and to discuss techniques that would
      maximize yield rates and minimize complications. Design, Setting, and
      Participants: A retrospective, consecutive observational case series was
      conducted from January 29, 2013, to May 23, 2017, at Retina Consultants of
      Houston and Houston Methodist Hospital among 44 patients with uveal melanoma of
      the ciliary body or choroid. Interventions or Exposures: Fine-needle aspiration
      biopsy and intraoperative histopathologic analysis prior to iodine 125
      brachytherapy. Main Outcomes and Measures: Tumor locations and dimensions were
      identified by histopathologic analysis and B-scan ultrasonography. Either
      transscleral or transvitreal biopsy was performed for tumors anterior to the
      equator and posterior to the equator, respectively. Biopsy specimens were checked
      for adequacy intraoperatively. Specimens were examined using hematoxylin-eosin,
      double immunostain with human melanoma black 45 and Ki67, and gene expression
      profile. Results: A total of 44 patients were included in the study, with a mean
      (SD) age of 63.3 (12.7) years (21 men [47.7%]; 23 women [52.3%]). Median tumor
      height was 2.7 mm (interquartile range, 2.3- 2.9 mm). Forty of 44 biopsy samples
      (90.9%; 95% CI, 82.4%-99.4%) yielded adequate cells for gene expression profile
      analysis. Transscleral and transvitreal yield rates were 11 of 11 (100%) and 29
      of 33 (87.9%), respectively. Most localized vitreous hemorrhages were resolved by
      3 months. There was a moderate association between localized vitreous hemorrhage
      and transvitreal biopsy method, for which the phi value was -0.526 (95% CI, 
      0.712 to -0.157; P < .001). Conclusions and Relevance: These findings suggest
      intraoperative adequacy evaluation of fine-needle aspiration biopsy specimens
      leads to high yield and is more informative for patients.

PMID- 29596553
TI  - Association of Vitamin A Supplementation With Disease Course in Children With
      Retinitis Pigmentosa.
AB  - Importance: While oral vitamin A supplementation is considered to potentially
      slow loss of retinal function in adults with retinitis pigmentosa and normal
      liver function, little data from children with this disease are available.
      Objective: To compare disease courses in children with retinitis pigmentosa
      taking or not taking vitamin A supplementation. Design, Setting, and
      Participants: Retrospective, nonrandomized comparison of vitamin A and control
      cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service
      of the Massachusetts Eye and Ear Infirmary. The study included children with
      different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and
      25 not taking vitamin A. The dates for patient evaluations ranged from June 1976
      to July 2016, and the data analysis occurred in October 2016. Interventions: Age
      adjusted dose of oral vitamin A palmitate (<=15 000 IU/d). Main Outcomes and
      Measures: Mean exponential rates of change of full-field cone electroretinogram
      amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression
      without and with adjusting for potential confounders. Results: Of the 55 children
      in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9]
      years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the
      25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2
      [1.7] years; and 25 (100%) were white. The estimated mean rates of change with
      the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A
      cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort
      (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263
      loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of
      decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI
      for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to
      ocular safety, the mean exponential rates of change of visual field area and
      visual acuity and the incidences of falling to a visual field diameter of 20
      degrees  or less or a visual acuity of 20/200 or less in at least 1 eye did not
      differ by cohort. Conclusions and Relevance: A vitamin A palmitate supplement was
      associated with a slower loss of cone electroretinogram amplitude in children
      with retinitis pigmentosa. Although the relatively small-sample, retrospective,
      nonrandomized design does not allow a test of causation and is subject to
      possible biases, these findings support consideration of an age-adjusted dose of
      vitamin A in the management of most children with the common forms of retinitis
      pigmentosa.

PMID- 29596554
TI  - A Novel Approach to the National Resident Matching Program-The Star System.

PMID- 29596555
TI  - Standardized Margin Assessment Is Needed Before Implementing Negative Margin as a
      Quality Measure.

PMID- 29596556
TI  - Uveal Melanoma Associated With Myotonic Dystrophy: A Report of 6 Cases.
AB  - Importance: Patients with myotonic dystrophy (MD) have an increased risk of
      malignancy including uveal melanoma. This case series further explores the
      association between these 2 diseases. Objective: To describe a cohort of patients
      with uveal melanoma associated with MD, including a case of iris melanoma, and MD
      associated uveal melanoma in relatives. Design, Setting, and Participants:
      Retrospective case series at 3 tertiary referral centers (Wills Eye Hospital,
      Philadelphia, Pennsylvania; Mayo Clinic, Rochester, Minnesota; and Moorfields Eye
      Hospital, London, England), between January 1, 2000, and August 31, 2017. The
      study included 6 patients with MD and uveal melanoma. Main Outcomes and Measures:
      Melanoma response to treatment and development of metastatic disease. Results:
      There were 6 patients, 4 men and 2 women, with MD and uveal melanoma. The mean
      patient age at melanoma diagnosis was 47 years (median, 43 years; range, 30-67
      years), and the tumor involved the choroid in 5 patients (83%) and iris in 1
      patient (17%). The diagnosis of MD was known since young adulthood in 2 patients
      (33%) and was discovered in adulthood in 4 patients (67%). The main clinical
      features of MD included muscle weakness (n = 5; 83%), myotonia (n = 4; 67%),
      polychromatic cataract (n = 4; 67%), complications with general anesthesia (n =
      4; 67%), myalgia (n = 3; 50%), cardiac arrhythmia (n = 2; 33%), and frontal
      baldness (n = 2; 33%). Genetic testing revealed MD type 1 (4 of 4 tested
      patients), and 2 patients demonstrated positive family history of MD with classic
      clinical features and preferred no testing. Melanoma treatment included plaque
      radiotherapy (n = 4; 67%), photodynamic therapy (n = 1; 17%), and declined
      treatment (n = 1; 17%). At follow-up of 6, 6, 41, 42, and 87 months (5 patients),
      findings included melanoma regression (4 of 5 tumors), melanoma recurrence (1 of
      5 tumors), and no metastatic disease (5 of 5 patients). Conclusions and
      Relevance: Six adult patients with MD demonstrated uveal melanoma involving the
      choroid or iris, emphasizing the association between these 2 diseases. Further
      research seems warranted to explore the pathogenesis of uveal melanoma in MD.
      These findings support the consideration of ophthalmic examination for uveal
      melanoma in patients with MD.

PMID- 29596557
TI  - By Sleight of Hand, Prognosis Determined-Even for Small Choroidal Melanoma.

PMID- 29596558
TI  - Tubular Neck Mass.

PMID- 29596559
TI  - Stochastic modelling of tree architecture and biomass allocation: application to
      teak (Tectona grandis L. f.), a tree species with polycyclic growth and leaf
      neoformation.
AB  - Background and aims: For a given genotype, the observed variability of tree forms
      results from the stochasticity of meristem functioning and from changing and
      heterogeneous environmental factors affecting biomass formation and allocation.
      In response to climate change, trees adapt their architecture by adjusting growth
      processes such as pre- and neoformation, as well as polycyclic growth. This is
      the case for the teak tree. The aim of this work was to adapt the plant model,
      GreenLab, in order to take into consideration both these processes using existing
      data on this tree species. Methods: This work adopted GreenLab formalism based on
      source-sink relationships at organ level that drive biomass production and
      partitioning within the whole plant over time. The stochastic aspect of phytomer
      production can be modelled by a Bernoulli process. The teak model was designed,
      parameterized and analysed using the architectural data from 2- to 5-year-old
      teak trees in open field stands. Key results: Growth and development parameters
      were identified, fitting the observed compound organic series with the
      theoretical series, using generalized least squares methods. Phytomer
      distributions of growth units and branching pattern varied depending on their
      axis category, i.e. their physiological age. These emerging properties were in
      accordance with the observed growth patterns and biomass allocation dynamics
      during a growing season marked by a short dry season. Conclusions: Annual growth
      patterns observed on teak, including shoot pre- and neoformation and polycyclism,
      were reproduced by the new version of the GreenLab model. However, further
      updating is discussed in order to ensure better consideration of radial variation
      in basic specific gravity of wood. Such upgrading of the model will enable teak
      ideotypes to be defined for improving wood production in terms of both volume and
      quality.

PMID- 29596560
TI  - The Influence of Preoperative Interventions on Postoperative Surgical Wound
      Healing in Patients Without Risk Factors: A Systematic Review.
AB  - Background: Poor wound healing and scar formation remain critical problems in
      daily surgical practice. Generally, most attention is paid to intra- and
      postoperative interventions to improve wound healing after surgery, while
      preoperative interventions remain unsatisfactorily explored. Objectives: In this
      systematic review, the available literature on the beneficial effects of
      preoperative interventions on wound healing and scar formation have been
      summarized and compared. Methods: A comprehensive and systematic search has been
      conducted in MEDLINE, Pubmed, Embase, Web of Science, and Cochrane, supplemented
      by reference and citation tracking. All preoperative interventions and all
      clinically relevant outcome parameters have been considered for inclusion, due to
      the expected limited availability of literature. Results: A total of 13 studies
      were included, which were all randomized trials. No cohort studies or
      retrospective studies have been identified. All studies described different
      preoperative interventions and outcome parameters and could hence not be pooled
      and compared. Eight studies showed significantly better wound healing after a
      preoperative intervention. The individual studies have been summarized in this
      review. Conclusions: This systemic review shows that preoperative interventions
      can be beneficial in improving wound healing and scar formation. In selected
      cases, wound healing was found to benefit from a higher preoperative body
      temperature, topical vitamin E application, and low patient stress levels. Level
      of Evidence 2: 

PMID- 29596561
TI  - Standardization of left atrial, right ventricular, and right atrial deformation
      imaging using two-dimensional speckle tracking echocardiography: a consensus
      document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.
AB  - The EACVI/ASE/Industry Task Force to standardize deformation imaging prepared
      this consensus document to standardize definitions and techniques for using two
      dimensional (2D) speckle tracking echocardiography (STE) to assess left atrial,
      right ventricular, and right atrial myocardial deformation. This document is
      intended for both the technical engineering community and the clinical community
      at large to provide guidance on selecting the functional parameters to measure
      and how to measure them using 2D STE.This document aims to represent a
      significant step forward in the collaboration between the scientific societies
      and the industry since technical specifications of the software packages designed
      to post-process echocardiographic datasets have been agreed and shared before
      their actual development. Hopefully, this will lead to more clinically oriented
      software packages which will be better tailored to clinical needs and will allow
      industry to save time and resources in their development.

PMID- 29596563
TI  - Error in Abstract and Tables.

PMID- 29596564
TI  - Pulsatile Tinnitus With Imaging.

PMID- 29596562
TI  - Salinity induction of recycling Crassulacean acid metabolism and salt tolerance
      in plants of Talinum triangulare.
AB  - Background and Aims: Crassulacean acid metabolism (CAM) can be induced by
      salinity, thus conferring the plant higher water-use efficiency. Talinum
      triangulare does not frequently encounter salt in its natural habitat but is
      cultivated in soils that may become salinized. Here we examined whether plants of
      T. triangulare can grow in saline soils and show salt-induced CAM. Methods: Leaf
      gas exchange, carbon isotopic ratio (delta13C), nocturnal acid accumulation
      (DeltaH+), water relations, photosynthetic pigment and mineral contents, leaf
      anatomy and growth were determined in greenhouse in plants irrigated with 0, 150,
      300 and 400 mm NaCl. Key Results: Salinity reduced gas exchange and induced CAM,
      DeltaH+ reaching 50.2 MUmol H+ g-1 fresh mass under 300 mm NaCl. No nocturnal CO2
      uptake, but compensation, was observed. Values of delta13C were lowest under 0
      and 400 mm NaCl, and highest under 150 and 300 mm. The difference in osmotic
      potential (psis) between control and treated plants averaged 0.45 MPa for the
      three [NaCl] values, the decrease in psis being accounted for by up to 63 % by
      Na+ and K+. Pigment contents were unaffected by treatment, suggesting lack of
      damage to the photosynthetic machinery. Changes in stomatal index with unchanged
      stomatal density in newly expanded leaves suggested inhibited differentiation of
      epidermal cells into stomata. Whole-leaf and parenchymata thickness increased
      under 150 and 300 mm NaCl. Only plants irrigated with 400 mm NaCl showed
      reductions in biomass (stems, 41 %; reproductive structures, 78 %). The K/Na
      molar ratio decreased with [NaCl] from 2.0 to 0.4. Conclusions: The operation of
      CAM in the recycling mode was evidenced by increased DeltaH+ with no nocturnal
      CO2 uptake. Talinum triangulare can be classified as a halo-tolerant species
      based on its low K/Na molar ratio under salinity and the relatively small
      reduction in growth only at the highest [NaCl].

PMID- 29596565
TI  - Midlife Predictors of Health-Related Quality of Life in Older Women.
AB  - Background: Midlife represents an important time to evaluate health status and
      health behaviors that may affect health-related quality of life (HRQL) in later
      years. This study examines change in women's HRQL over 11 years from ages 47-59
      to 57-69 and identifies midlife characteristics that predict HRQL at older ages.
      Methods: Physical (PCS) and mental component summaries (MCS) of the SF-36 were
      used to assess HRQL from 2002 to 2013 in 2,614 women from the Study of Women's
      Health Across the Nation (SWAN), a multiethnic/racial cohort study. We used
      locally weighted scatterplot smoothing (LOESS) models to obtain unadjusted
      predicted mean trajectories of PCS and MCS as a function of age. Results: LOESS
      predicted PCS declined from 51.6 to 47.1, whereas MCS increased from 49.2 to
      53.1. In multivariable models, controlling for baseline PCS, higher baseline
      physical activity (p = .002) and increase in physical activity from baseline (p <
      .0001) predicted better PCS. Time since baseline (ie, aging; p < .001), higher
      baseline body mass index (p < .0001), increased body mass index over time (p <
      .0001), smoking (p < .05), two or more medical conditions (p < .0001), sleep
      problems (p < .0001), and urinary incontinence (p < .0001) were related to lower
      PCS. Early (p = .004) and late postmenopause (p = .001; vs. premenopause) and
      aging (p = .05) predicted higher MCS. Predictors of lower MCS were less than very
      good health (p < .0001), sleep problems (p < .0001), stressful life events (p <
      .0001), higher perceived stress (p < .0001), and higher trait anxiety (p = .004).
      Race/ethnicity was related to MCS, but not PCS. Conclusions: Several potentially
      modifiable midlife factors, such as improved sleep hygiene, physical activity,
      and body mass index, might improve HRQL for older women.

PMID- 29596566
TI  - Accelerating Accelerometer Research in Aging.

PMID- 29596567
TI  - Malignant disease as a comorbidity in patients with severe aortic stenosis:
      clinical presentation, outcomes, and management.
AB  - Aim: To investigate the effect of malignancy on the outcomes of patients with
      severe aortic stenosis (AS) and the management strategy for AS with malignancy.
      Methods and results: Using data of 3815 patients with severe AS in a
      retrospective multicentre registry [CURRENT AS (Contemporary outcomes after
      sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry],
      we compared 3-year clinical outcomes among three groups based on malignancy
      status: with malignancy currently under treatment including best supportive care
      (malignancy group), with a history of malignancy without any current treatment
      (past history group), or without history of malignancy (no malignancy group).
      Patients in the malignancy group (n = 124) were more often men and had higher
      prevalence of low body mass index, recurrence of malignancy, anaemia, and
      asymptomatic status, despite comparable surgical risks and echocardiographic
      parameters. The malignancy group or the past history group (n = 389) had
      significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI
      (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for
      malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52)
      than that of the no malignancy group (n = 3302). The excess risk for aortic valve
      related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48
      1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the
      malignancy group, the treatment strategy (surgery: n = 16, conservative
      management: n = 108) was determined based on the clinical status of AS or life
      expectancy. Conclusions: Malignancy had marked effect on all-cause death and
      malignancy-related death in patients with severe AS. History of malignancy also
      had a smaller but significant effect on mortality.

PMID- 29596568
TI  - Effects of the Tongue-in-Groove Maneuver on Nasal Tip Rotation.
AB  - Background: A change in nasal tip rotation is a very common maneuver performed
      during rhinoplasty. Among the many techniques used to achieve this goal is the
      tongue-in-groove (TIG). Objectives: This study addresses the long-term effect of
      the TIG on the nasal tip rotation 1 year after rhinoplasty. Methods: The authors
      prospectively identified patients who were submitted to a rhinoplasty with a TIG
      maneuver over a period of 1 year. The angle of rotation was measured along the
      nostril axis angle. The data were analyzed using the t test and a linear
      regression model. Results: Seventeen patients were included. The average
      preoperative tip rotation was 93.95 degrees  (SD, 3.12 degrees ). Immediate
      postoperative tip rotation averaged 114.47 degrees  (SD, 3.79 degrees ). At the 1
      year follow-up appointment, the tip rotation averaged 106.55 degrees  (SD, 3.54
      degrees ). There was a significant loss of rotation at the 1-year postoperative
      visit (P < 0.0001), with an average loss of 7.9 degrees  (SD, 3.25 degrees ),
      which amounted to 6.8%. The preoperative rotation didn't affect the amount of
      loss of rotation (P = 0.04). It can be estimated that, for every degree of
      rotation that is changed at surgery, the tip can be expected to lose 0.35 degrees
      over the first year. Conclusions: TIG is a more dependable technique than the
      ones that rely on healing and contraction to obtain rotation. Our data
      demonstrated a significant loss of rotation during the first year. This suggests
      that the surgeon needs to slightly overcorrect the tip rotation to account for
      this loss. Level of Evidence 4: 

PMID- 29596569
TI  - Interferon-gamma inhibits seminal plasma induction of colony-stimulating factor 2
      in mouse and human reproductive tract epithelial cells.
AB  - Seminal fluid interacts with the female reproductive tract to initiate a
      permissive immune response that facilitates embryo implantation and pregnancy
      success. The immune-regulatory cytokine interferon-gamma (IFNG), which can be
      elevated in seminal plasma, is associated with reduced fertility. Here, we
      investigated how IFNG influences the female immune response to seminal fluid. In
      human Ect1 cervical epithelial cells, IFNG added at physiologically relevant
      concentrations substantially impaired seminal plasma-induced synthesis of key
      cytokines colony-stimulating factor 2 (CSF2) and interleukin-6 (IL6). Seminal
      fluid-induced CSF2 synthesis was also suppressed in the uterus of mice in vivo,
      when IFNG was delivered transcervically 12 h after mating. Transforming growth
      factor B1 (TGFB1) is the major seminal fluid signaling factor which elicits CSF2
      induction, and IFNG exhibited potent dose-dependent suppression of CSF2 synthesis
      induced by TGFB1 in murine uterine epithelial cells in vitro. Similarly, IFNG
      suppressed TGFB1-mediated CSF2 induction in Ect1 cells and human primary cervical
      epithelial cells; however, IL6 regulation by IFNG was independent of TGFB1.
      Quantitative PCR confirmed that CSF2 regulation by IFNG in Ect1 cells occurs at
      the gene transcription level, secondary to IFNG suppression of TGFBR2 encoding
      TGFB receptor 2. Conversely, TGFB1 suppressed IFNG receptor 1 and 2 genes IFNGR1
      and IFNGR2. These data identify IFNG as a potent inhibitor of the TGFB-mediated
      seminal fluid interaction with relevant reproductive tract epithelia in mice and
      human. These findings raise the prospect that IFNG in the male partner's seminal
      fluid impairs immune adaptation for pregnancy following coitus in women.

PMID- 29596570
TI  - Integrated Forehead and Temporal Augmentation Using 3D Printing-Assisted Methyl
      Methacrylate Implants.
AB  - Background: Achieving aesthetic results with forehead augmentation procedures
      remains challenging. We have developed a method of integrated forehead and
      temporal augmentation using a three-dimensional (3D) printing-assisted methyl
      methacrylate implant. Objectives: The study objective was to assess the
      importance of combined temporal augmentation when performing forehead
      augmentation. Methods: We identified 34 patients (from 2000 to 2010) who
      underwent forehead augmentation with a methyl methacrylate implant contoured in
      situ during surgery and 41 patients (from 2010 to 2016) who underwent integrated
      forehead and temporal augmentation with a prefabricated methyl methacrylate
      implant. We conducted a retrospective chart review of patient data including
      operation time, complications, and instances of revision surgery. Two blinded
      plastic surgeons scored the aesthetic results of the operations on a 4-point
      scale (1, poor, to 4, excellent) based on preoperative and posttreatment
      photographs. Results: The integrated augmentation method resulted in a lower
      frequency of posttreatment implant removal (one [2%] vs. six [18%]; P < .05), a
      lower frequency of filler injection for touch up (one [2%] vs. six [18%]; P <
      .05), and higher mean aesthetic scores (3.7 +/- 0.5 vs. 2.2 +/- 1.0; P < . 001)
      compared to the forehead augmentation method. There was no statistically
      significant difference in surgical complications between the two groups.
      Conclusions: Integrated forehead and temporal augmentation using a 3D printing
      assisted methyl methacrylate implant may be the optimal available procedure,
      enabling the custom fabrication of contours requested by the patient and
      providing a rejuvenating and balancing effect on facial appearance. Level of
      Evidence 3: 

PMID- 29596572
TI  - Structural and functional analyses of microbial metabolic networks reveal novel
      insights into genome-scale metabolic fluxes.
AB  - We present here an integrated analysis of structures and functions of genome
      scale metabolic networks of 17 microorganisms. Our structural analyses of these
      networks revealed that the node degree of each network, represented as a
      (simplified) reaction network, follows a power-law distribution, and the
      clustering coefficient of each network has a positive correlation with the
      corresponding node degree. Together, these properties imply that each network has
      exactly one large and densely connected subnetwork or core. Further analyses
      revealed that each network consists of three functionally distinct subnetworks:
      (i) a core, consisting of a large number of directed reaction cycles of enzymes
      for interconversions among intermediate metabolites; (ii) a catabolic module,
      with a largely layered structure consisting of mostly catabolic enzymes; (iii) an
      anabolic module with a similar structure consisting of virtually all anabolic
      genes; and (iv) the three subnetworks cover on average ~56, ~31 and ~13% of a
      network's nodes across the 17 networks, respectively. Functional analyses
      suggest: (1) cellular metabolic fluxes generally go from the catabolic module to
      the core for substantial interconversions, then the flux directions to anabolic
      module appear to be determined by input nutrient levels as well as a set of
      precursors needed for macromolecule syntheses; and (2) enzymes in each subnetwork
      have characteristic ranges of kinetic parameters, suggesting optimized metabolic
      and regulatory relationships among the three subnetworks.

PMID- 29596571
TI  - Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in
      atherosclerosis progression.
AB  - Aims: GTP cyclohydrolase I catalyses the first and rate-limiting reaction in the
      synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide
      synthases (NOS). Both eNOS and iNOS have been implicated in the progression of
      atherosclerosis, with opposing effects in eNOS and iNOS knockout mice. However,
      the pathophysiologic requirement for BH4 in regulating both eNOS and iNOS
      function, and the effects of loss of BH4 on the progression of atherosclerosis
      remains unknown. Methods and results: Hyperlipidemic mice deficient in Gch1 in
      endothelial cells and leucocytes were generated by crossing Gch1fl/flTie2cre mice
      with ApoE-/- mice. Deficiency of Gch1 and BH4 in endothelial cells and myeloid
      cells was associated with mildly increased blood pressure. High fat feeding for 6
      weeks in Gch1fl/flTie2CreApoE-/- mice resulted in significantly decreased
      circulating BH4 levels, increased atherosclerosis burden and increased plaque
      macrophage content. Gch1fl/flTie2CreApoE-/- mice showed hallmarks of endothelial
      cell dysfunction, with increased aortic VCAM-1 expression and decreased
      endothelial cell dependent vasodilation. Furthermore, loss of BH4 from pro
      inflammatory macrophages resulted in increased foam cell formation and altered
      cellular redox signalling, with decreased expression of antioxidant genes and
      increased reactive oxygen species. Bone marrow chimeras revealed that loss of
      Gch1 in both endothelial cells and leucocytes is required to accelerate
      atherosclerosis. Conclusion: Both endothelial cell and macrophage BH4 play
      important roles in the regulation of NOS function and cellular redox signalling
      in atherosclerosis.

PMID- 29596573
TI  - Longevity Around the Turn of the 20th Century: Life-Long Sustained Survival
      Advantage for Parents of Today's Nonagenarians.
AB  - Members of longevous families live longer than individuals from similar birth
      cohorts and delay/escape age-related diseases. Insight into this familial
      component of longevity can provide important knowledge about mechanisms
      protecting against age-related diseases. This familial component of longevity was
      studied in the Leiden Longevity Study which consists of 944 longevous siblings
      (participants), their parents (N = 842), siblings (N = 2,302), and spouses (N =
      809). Family longevity scores were estimated to explore whether human longevity
      is transmitted preferentially through the maternal or paternal line. Standardized
      mortality ratios (SMRs) were estimated to investigate whether longevous siblings
      have a survival advantage compared with longevous singletons and we investigated
      whether parents of longevous siblings harbor a life-long sustained survival
      advantage compared with the general Dutch population by estimating lifetime SMRs
      (L-SMRs). We found that sibships with long-lived mothers and non-long-lived
      fathers had 0.41 (p = .024) less observed deaths than sibships with long-lived
      fathers and non-long-lived mothers and 0.48 (p = .008) less observed deaths than
      sibships with both parents non-long lived. Participants had 18.6 per cent less
      deaths compared with matched singletons and parents had a life-long sustained
      survival advantage (L-SMR = 0.510 and 0.688). In conclusion, genetic longevity
      studies may incorporate the maternal transmission pattern and genes influencing
      the entire life-course of individuals.

PMID- 29596574
TI  - Efficacy and Safety of Autologous Fat Transfer in Facial Reconstructive Surgery:
      A Systematic Review and Meta-analysis.
AB  - Importance: The use of autologous fat transfer (AFT) or lipofilling for
      correcting contour deformities is seen as one of the major breakthroughs in
      reconstructive plastic surgery. Its applications in facial reconstructive surgery
      have been of particular interest owing to the prospect of achieving autologous
      reconstruction by a minimally invasive approach. However, its unpredictability
      and variable degree of resorption have limited its utility and much skepticism
      still exists regarding its efficacy. Furthermore, more than 2 decades of clinical
      research have produced a highly fragmented body of evidence that has not been
      able to provide definite answers. Objective: To investigate the safety and
      efficacy of AFT in facial reconstruction through a systematic review and meta
      analysis. Data Sources: A literature search was performed in PubMed, Embase, and
      the Cochrane Library from inception to October 11, 2017. Study Selection: All
      published studies investigating the efficacy and safety of AFT in facial
      reconstructive surgery. Data Extraction and Synthesis: Two independent reviewers
      performed data extraction systematically, adhering to the PRISMA guidelines.
      Summary measures were pooled in a random-effects model meta-analysis. Main
      Outcomes and Measures: The patient and surgeon satisfaction, graft survival,
      number of AFT sessions, and the incidence of AFT-related complications were the
      main outcomes of interest in this meta-analysis. Results: This systematic review
      resulted in the inclusion 52 relevant studies consisting of 1568 unique patients.
      These included 4 randomized clinical trials, 11 cohort studies, and 37 case
      series. The overall follow-up averaged 1.3 years after AFT. Meta-analysis
      revealed a very high overall patient satisfaction rate of 91.1% (95% CI, 85.1%
      94.8%) and overall surgeon satisfaction rate of 88.6% (95% CI, 83.4%-92.4%). The
      number of AFT sessions required to achieve the desired result was 1.5 (95% CI,
      1.3-1.7) and 50% to 60% of the injected volume was retained at 1 year. Only 4.8%
      (95% CI, 3.3%-6.9%) of procedures resulted in clinical complications. Conclusions
      and Relevance: To our knowledge, this study provides the first overview of the
      current knowledge about AFT in facial reconstructive surgery. Our results confirm
      that AFT is an effective technique for treating soft-tissue deformities in the
      head and neck, with low rate of minor complications. Level of Evidence: NA.

PMID- 29596575
TI  - Why Are Patients With Giardiasis Not Treated Earlier? Two Sides of the Same Coin.

PMID- 29596576
TI  - The end for individualized dosing in IVF ovarian stimulation? Reply to letters-to
      the-editor regarding the OPTIMIST papers.

PMID- 29596578
TI  - OPTIMIST trial: optimistic evidence?

PMID- 29596577
TI  - Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not
      with coronary artery disease.
AB  - Aims: Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high
      density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A
      rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported
      to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary
      artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment
      might be an independent marker of cardiovascular risk. We tested the hypothesis
      that alleles in or close to SCARB1 that associate with elevated levels of HDL-C
      also associate with increased risk of CAD in the relatively homogeneous
      population of Iceland. Methods and results: Using a large resource of whole
      genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that
      we examined for association with HDL-C (n = 136 672). Three rare SCARB1
      mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency =
      0.2%) associate with elevated levels of HDL-C (p.G319V: beta = 11.1 mg/dL, P =
      8.0 * 10-7; p.V111M: beta = 8.3 mg/dL, P = 1.1 * 10-6; p.V32M: beta = 10.2 mg/dL,
      P = 8.1 * 10-4). These mutations do not associate with CAD (36 886 cases/306 268
      controls) (odds ratio = 0.90, 95% confidence interval 0.67-1.22, P = 0.49),
      despite effects on HDL-C comparable to that reported for p.P376L, both in terms
      of direction and magnitude. Furthermore, HDL-C raising alleles of three common
      SCARB1 non-coding variants, including one previously unreported (rs61941676-C:
      beta = 1.25 mg/dL, P = 1.7 * 10-18), and of one low frequency coding variant
      (p.V135I) that independently associate with higher HDL-C, do not confer increased
      risk of CAD. Conclusion: Elevated HDL-C due to genetically compromised SR-BI
      function is not a marker of CAD risk.

PMID- 29596579
TI  - Observed smoking and tobacco pack display in Australian outdoor cafes 2 years
      after implementation of plain packaging.
AB  - Background: Implementation of tobacco plain packaging (PP) in Australia in
      December 2012 was associated with significant reductions in the percentage of
      patrons at outdoor cafes observed to be displaying tobacco packs and actively
      smoking, immediately post-implementation and 1 year later. This study examines
      whether these positive effects were sustained through to 2 years post-PP.
      Methods: An observational study conducted at cafes, restaurants and bars with
      outdoor seating in Melbourne, Australia documented the number of: patrons;
      patrons actively smoking; tobacco packs on display; orientation and type of
      displayed packs and whether or not children were present. Data were collected pre
      PP (2012), early post-PP (2013), 1 year post-PP (2014) and 2 years post-PP
      (2015). Multilevel Poisson regressions analyzed changes in each outcome,
      adjusting for important covariates. Results: Overall, positive effects of PP
      implementation on tobacco pack display and active smoking were not fully
      sustained through to 2 years post-PP for the total sample. Interactions between
      phase and the presence of children indicated that pack display and active smoking
      were lower in all post-implementation phases (compared with pre-PP) at venues
      where children were present but not at venues where children were not present.
      Conclusions: Children at outdoor cafes were still being exposed to less tobacco
      packaging and active smoking, 2 years after implementation of the packaging
      changes. More regular refreshment of graphic health warnings is likely to be
      required to sustain these effects, and to reduce pack display behaviour at venues
      with no children.

PMID- 29596580
TI  - Anterior Chamber Chemotherapy in Retinoblastoma-Necessary but Not Sufficient for
      Aqueous Seeding Control.

PMID- 29596581
TI  - Vitamin A for Children With Retinitis Pigmentosa: An Unresolved Mystery.

PMID- 29596583
TI  - Corrigendum.

PMID- 29596584
TI  - High-volume intensive training course: a new paradigm for video-assisted
      thoracoscopic surgery education.
AB  - OBJECTIVES: The emergence of ultra-high-volume centres promises new opportunities
      for thoracic surgical training. The goal of this study was to investigate the
      effectiveness of a novel observership course in teaching video-assisted
      thoracoscopic surgery (VATS) at an ultra-high-volume centre. METHODS: Two-week
      courses in VATS at a specialist unit now performing >10 000 major lung resections
      annually (>50 daily on average) were attended by 230 surgeons from around the
      world from 2013 to 2016. An online survey preserving responder anonymity was
      completed by 156 attendees (67.8%). RESULTS: Attendees included 37% from Western
      Europe, 18% from Eastern Europe and 17% from Latin America. Experience with open
      thoracic surgery for more than 5 years was reported by 67%, but 79% had less than
      5 years of VATS lobectomy experience. During the course, 70% observed over 30
      uniportal VATS operations (including 38% observing over 50), and 69% attended an
      animal wet lab. Although 72% of the responders attended the course less than 12
      months ago, the number of ports used (P < 0.001), operation times (P < 0.001) and
      conversion rates (P < 0.001) reported by the responders were reduced
      significantly after the course. Improvements in the problem areas of tissue
      retraction, instrumentation, stapler application and coordination with the
      assistant during VATS were reported by 56%, 57%, 58% and 53%, respectively. Of
      those who had attended other VATS courses previously, 87% preferred the training
      from this high-volume course. CONCLUSIONS: High-volume intensive observership
      training at an ultra-high-volume centre may improve VATS proficiency in a short
      period of time, and may provide a time-efficient modality for future thoracic
      surgical training.

PMID- 29596582
TI  - Prevalence of Posttraumatic Stress Disorder in Prisoners.
AB  - People involved with criminal justice frequently are exposed to violence and
      traumatic experiences. This may lead to posttraumatic stress disorder (PTSD);
      however, no review, to our knowledge, has synthetized findings in this setting.
      We conducted a systematic review and meta-analysis to estimate prevalence rates
      of PTSD in prison populations. Original studies in which prevalence rates of PTSD
      in unselected samples of incarcerated people were reported were systematically
      searched between 1980 and June 2017. Data were pooled using random-effects meta
      analysis, and sources of heterogeneity for prespecified characteristics were
      assessed by meta-regression. We identified 56 samples comprising 21,099
      imprisoned men and women from 20 countries. Point prevalence of PTSD ranged from
      0.1% to 27% for male, and from 12% to 38% for female prisoner populations. The
      random-effects pooled point prevalence was 6.2% (95% confidence interval: 3.9,
      9.0) in male prisoners and 21.1% (95% confidence interval: 16.9, 25.6) in female
      prisoners. The heterogeneity between the included studies was very high. Higher
      prevalence was reported in samples of female prisoners, smaller studies (n <=
      200), and for investigations based in high-income countries. Existing evidence
      shows high levels of PTSD among imprisoned people, especially women. Psychosocial
      interventions to prevent violence, especially against children and women, and to
      mitigate its consequences in marginalized communities must be improved. Trauma
      informed approaches for correctional programs and scalable PTSD treatments in
      prisons require further consideration.

PMID- 29596585
TI  - Poor definition of poor-ovarian response results in misleading clinical
      recommendations.

PMID- 29596587
TI  - Postoperative Facial Baroparesis While Flying: A Rare Complication of
      Decompressing a Facial Nerve Schwannoma.

PMID- 29596586
TI  - A new strategy to decrease cardiac injury in aged heart following ischaemia
      reperfusion: enhancement of the interaction between AMPK and SIRT1.

PMID- 29596588
TI  - Incidence of and Risk Factors Associated With Age-Related Macular Degeneration:
      Four-Year Follow-up From the ALIENOR Study.
AB  - Importance: While the prevalence of age-related macular degeneration (AMD)
      differs according to continents and races/ethnicities, its incidence in the
      European continent has been scarcely documented. Objective: To describe the
      incidence and associated risk factors of AMD in elderly French individuals.
      Design, Setting, and Participants: This population-based cohort study of 963
      residents of Bordeaux, France, who were 73 years or older at baseline and
      participated in the Antioxydants, Lipides Essentiels, Nutrition et Maladies
      Oculaires (ALIENOR) Study between October 2, 2006, and December 21, 2012. Of 829
      participants at risk for incident AMD, 659 (79.5%) were observed for a mean (SD)
      duration of 3.8 (1.1) years. Data were analyzed from August 2016 to March 2017.
      Main Outcomes and Measures: Age-related macular degeneration was graded from
      retinal photographs and spectral-domain optical coherence tomography into 5
      exclusive stages: no AMD, early AMD1, early AMD2, late atrophic AMD, and late
      neovascular AMD. Results: Of the 659 eligible participants, 413 (62.7%) were
      women, and the mean (SD; range) age was 79.7 (4.4; 73-94) years. A total of 120
      incident cases of early AMD and 45 incident cases of advanced AMD were recorded.
      Incidence rates of early and advanced AMD were 79.9 (95% CI, 66.8-95.5) per 1000
      person-years and 18.6 (95% CI, 13.9-24.9) per 1000 person-years, respectively,
      corresponding to 5-year risks of 32.9% and 8.9%. Incidence of advanced AMD per
      1000 eye-years was 1.5 in eyes without any AMD at baseline, 42.4 in those with
      early AMD1, and 85.1 in those with early AMD2. In multivariate analysis without
      correction for multiple testing, progression from early to advanced AMD was
      associated with AMD grade in the fellow eye (hazard ratio [HR] according to
      grade, 13.0 [95% CI, 2.8-61.2] to 22.5 [95% CI, 2.6-195.9]), having smoked at
      least 20 pack-years (calculated as number of smoking years * mean number of
      cigarettes per day / 20; HR, 3.0; 95% CI, 1.4-6.5), and complement factor H (CFH)
      Y402H genotype (CC genotype: HR, 2.3; 95% CI, 1.0-5.3; TC genotype: HR, 1.5; 95%
      CI, 0.6-3.7). Incidence of early AMD was associated with early AMD in the fellow
      eye (early AMD1: HR, 2.6; 95% CI, 1.6-4.2; early AMD2: HR, 5.6; 95% CI, 3.3-9.4)
      and high plasma high-density lipoprotein cholesterol levels (HR, 1.2; 95% CI, 1.0
      1.4). Conclusions and Relevance: In this cohort, AMD incidence rates were similar
      to those observed in other European populations. This study suggests a high risk
      for incident early AMD in individuals with high plasma high-density lipoprotein
      cholesterol levels while confirming the high risk for progression from early to
      advanced AMD in heavy smokers and carriers of CFH Y402H at-risk genotypes.

PMID- 29596589
TI  - Psychosocial Factors Associated with Problem Drinking Among Substance Users with
      Poorly Controlled HIV Infection.
AB  - Aims: We aimed to identify psychosocial factors related to problem drinking among
      patients with poorly controlled human immunodeficiency virus (HIV) infection.
      Short Summary: We aimed to identify psychosocial factors related to problem
      drinking among those with poorly controlled HIV infection. Increased levels of
      interpersonal conflict were associated with greater severity of alcohol problems.
      Poorer mental health, medical mistrust and less satisfaction with one's physician
      related to excessive drinking. Methods: This secondary analysis used baseline
      data from a large multisite randomized controlled trial of substance users whose
      HIV infection was currently poorly controlled, from 11 urban hospitals across the
      USA. Participants were HIV-infected adult inpatients (n = 801; 67% male, 75%
      African American) with substance use histories. Participants self-reported on
      their drinking, perceived health, mental health, social relationships and patient
      provider relationship. Structural equation models examined psychosocial factors
      associated with problem drinking, controlling for demographic covariates.
      Results: Increased levels of interpersonal conflict were associated with greater
      severity of alcohol problems. Poorer mental health, medical mistrust and less
      satisfaction with one's physician were associated with excessive drinking.
      Conclusions: Several psychosocial factors, including interpersonal conflict, poor
      mental health (i.e. anxiety, depression and somatization), medical mistrust and
      less satisfaction with one's provider, were associated with problem drinking
      among HIV-infected substance users with poorly controlled HIV infection. The co
      occurrence of these concerns highlights the need for comprehensive services
      (including attention to problem drinking, social services, mental health and
      quality medical care) in this at-risk group.

PMID- 29596590
TI  - Physician Well-being and the Regenerative Power of Caring.

PMID- 29596591
TI  - Using electronic maternity records to estimate female genital mutilation in
      Lothian from 2010 to 2013.
AB  - Background: Female genital mutilation (FGM) is most commonly encountered in
      Africa and the Middle East, with migration from FGM-practicing countries meaning
      it is increasingly seen in Europe. Addressing FGM requires accurate information
      on who is affected but ascertainment is notoriously difficult. This study
      estimated FGM prevalence in women presenting for maternity care in the Lothian
      region of Scotland and compared this with that expected by extrapolation of
      survey data from women's country of birth. Methods: Electronic clinical records
      were linked to birth registration data to estimate FGM in the obstetric patients
      in Lothian from 2010 to 2013. Results: Among all, 107 women affected by FGM were
      detected, at a rate of 2.8/1000 pregnancies. Of 487 women from UNICEF-recognized
      FGM-practicing countries who accessed care, 87 (18%) had documented evidence of
      FGM (three quarters of whom came from Nigeria, Sudan or The Gambia). The
      prevalence was 54% of the level expected from the extrapolation method. Country
      of birth had a sensitivity of 81% for FGM. Conclusion: Women from FGM-practicing
      countries commonly access maternity care in Lothian. This confirms the need for
      ongoing training and investment in identifying and managing FGM. Matching
      electronic clinical records with birth registration data was a useful methodology
      in estimating the level of FGM in the maternity population. In a European country
      like Scotland with modest migrant numbers, asking country of birth during
      pregnancy and making sensitive enquiries could detect 81% of women with FGM.
      Extrapolation from maternal country of birth surveys grossly overestimates the
      true prevalence.

PMID- 29596592
TI  - Charter on Physician Well-being.

PMID- 29596593
TI  - Bilateral Cicatrizing Conjunctivitis in a Middle-aged Man.

PMID- 29596594
TI  - Early steroid withdrawal: a niche for anti-interleukin 2 receptor monoclonal
      antibodies?

PMID- 29596595
TI  - National Trends in Parental Human Papillomavirus Vaccination Intentions and
      Reasons for Hesitancy, 2010-2015.
AB  - Background: Human papillomavirus (HPV) vaccination uptake remains lower than
      other recommended adolescent vaccines in the United States. Parental attitudes
      are important predictors of vaccine uptake, yet little is known about how they
      have changed over time. Methods: Participants included US residents aged 13-17
      years with documented vaccination status who had received <3 doses of HPV vaccine
      whose parents responded to the National Immunization Survey-Teen, 2010-2015.
      Results: Of the 76971 participants, 63.0% were male, 58.8% were non-Hispanic
      white, and 14.4 years was the median age. The percentage of unvaccinated teens
      decreased from 2010 to 2015, yet, annually, parents of unvaccinated teens of both
      sexes most often reported that they were "not likely at all" to vaccinate their
      teen. The percentage decreased significantly from 41.5% to 31.2% (P < .001) for
      parents of unvaccinated females from 2010 to 2015 but did not change among
      parents of males from 2012 to 2015. Conversely, parents of undervaccinated teens
      of both sexes reported higher and increasing vaccination intent over time. In
      2015, nearly one-third of parents of unvaccinated teens reported that the vaccine
      was "not needed/necessary." Concerns about vaccine safety and side effects
      declined among parents of unvaccinated females but increased among parents of
      males (7.3% to 14.8%; P < .001). Conclusions: Although parental vaccination
      intent and knowledge improved over time, intent remains low and many parents
      still have significant concerns about HPV vaccination, even after series
      initiation. Multiple strategies are needed to improve series initiation and
      completion in the United States.

PMID- 29596596
TI  - beta-III-spectrin immunohistochemistry as a potential diagnostic tool with high
      sensitivity for malignant peripheral nerve sheath tumors.

PMID- 29596597
TI  - Rehabilitation Exercise Increases Physical Activity Levels in Severely Burned
      Children While Improving Aerobic Exercise Capacity and Strength.
AB  - This study tested the hypothesis that participation in a rehabilitation exercise
      program following hospital discharge would increase the level of physical
      activity in burned children than that seen in free-living nonburned children.
      Thirty-one severely burned children (12 +/- 3 years, 144 +/- 18 cm, 42 +/- 17 kg,
      48 +/- 12% TBSA burns) were matched to 31 nonburned children (12 +/- 3 y, 147 +/-
      17 cm, 45 +/- 15 kg) based on age and sex. Pedometers were used to track minutes
      and steps in burned children during their exercise rehabilitation and nonburned
      children under free-living conditions (healthy control). We found that the
      average minutes of activity per day was lower in burned children (56 +/-
      25minutes) than in nonburned children (74 +/- 28 minutes, P < .05). However, no
      difference was detected for average steps per day or week or maximal minutes in 1
      day or week. At discharge, burn children had peak torque and mean power values
      that were 61% of nonburned values, and exercise training improved these by 27 and
      28%, respectively (88 and 89% of nonburned values; each P <= .0001). Likewise,
      cardiorespiratory fitness at discharge was 72% of nonburned values, and exercise
      training improved fitness by 10% (82% of nonburned values, P < .05). Percentage
      TBSA burned was inversely associated with steps (r = -0.54, P = .001) and minutes
      of activity (r = -0.53, P = .002), accounting for 28-29% of the variability in
      burned children. These results show that, at discharge, burned children are
      capable of matching steps of physical activity levels seen in nonburned healthy
      children. Physical activity monitoring may be a viable option for continued
      improvement of physical exercise capacity when burned children are under free
      living conditions.

PMID- 29596598
TI  - A survey of practice and opinions on the use of topical antibiotics to prevent
      surgical site infection: more confusion than consensus.
AB  - Background: Surgical site infection (SSI) is one of the most common causes of
      healthcare-associated infection. Although the use of topical antibiotics to
      prevent SSI is not recommended by current guidelines, published studies document
      conflicting results and conclusions. Objectives: The objectives of this survey
      were to: (i) determine the extent of the use of topical antibiotics to prevent
      SSI in clinical practice; and (ii) gather the opinions of healthcare
      professionals most likely to be involved in their use. Methods: A questionnaire
      was circulated to members of BSAC and the European Wound Management Association
      (EWMA). Results: The questionnaire received 160 responses from a variety of
      healthcare professionals around the world. Most respondents (70%) did not have
      guidelines for the use of topical antibiotics for the prevention of SSI in their
      institution; if present, local guidance was based on national guidelines (20/31,
      65%). Most respondents did not use or recommend topical antibiotics to prevent
      SSI; of those that did, gentamicin collagen sponges were most commonly used
      (24/96 responses, 25%). Over half of the surgeons (18/33, 55%) who responded to
      the survey did not use topical antibiotics for the prevention of SSI but, when
      used, contaminated surgery (8/33, 24%) was the most commonly stated indication.
      Conclusions: There are diverse opinions and practices among healthcare
      professionals about the use of topical antibiotics for the prevention of SSI.
      This considerable, and possibly inappropriate, variation in clinical practice
      needs to be addressed as part of antibiotic stewardship.

PMID- 29596599
TI  - A new class of antibacterials, the imidazopyrazinones, reveal structural
      transitions involved in DNA gyrase poisoning and mechanisms of resistance.

PMID- 29596600
TI  - Burn Scar Evaluation Using the Cutometer(r) MPA 580 in Comparison to "Patient and
      Observer Scar Assessment Scale" and "Vancouver Scar Scale".
AB  - The effect of the "Patient and Observer Scar Assessment Scale" (POSAS) and
      "Vancouver Scar Scale" (VSS) on patients' quality of life and their correlation
      with objective scar assessment tools, such as the Cutometer(r), is not fully
      elucidated. In addition, long-term results of the dermal substitute Matriderm(r)
      used in combination with split-thickness skin grafting (STSG) remain unclear. We
      evaluated burn scars of 45 patients at least 2 years postburn injury using the
      Cutometer(r) MPA 580, the VSS, and the POSAS with three additional questions
      regarding quality of life and correlated the results. Study groups were: 1) scars
      following conservative treatment, 2) scars following STSG, and 3) scars following
      STSG in combination with Matriderm(r). Cutometer(r) measurements demonstrated
      better elastic qualities in the Matriderm(r) group compared with the STSG group.
      VSS and extended POSAS were rated best for the conservative group, followed by
      the STSG group and the Matriderm(r) group. There was a significant correlation
      between POSAS and VSS, quality of life and the objective Cutometer(r)
      measurements. Conservatively treated superficial dermal burns do not reach the
      elastic qualities of healthy skin, and the use of Matriderm(r) significantly
      improves the long-term elastic qualities of STSG in deep dermal and full
      thickness burns 2 years post injury. Results from the VSS and the POSAS correlate
      with restrictions in the quality of life of patients and also with objective
      Cutometer(r) measurements and are therefore useful tools in scar evaluation
      following burn injury.

PMID- 29596601
TI  - Response to Escobedo et al.

PMID- 29596602
TI  - Radiation of Bactrocera dorsalis (Diptera: Tephritidae) Eggs to Improve the Mass
      Rearing of Diachasmimorpha longicaudata (Hymenoptera: Braconidae).
AB  - This study explored the potential for Bactrocera dorsalis (Hendel) (Diptera:
      Tephritidae) larvae hatched from irradiated eggs as hosts for Diachasmimorpha
      longicaudata (Ashmead) (Hymenoptera: Braconidae). B. dorsalis eggs of three
      different ages (12-, 24-, and 36-h old) were analyzed for hatchability, pupation
      rate, pupal weight, emergence rate, and sex ratio after exposure to different
      doses of radiation (5 and 10 Gy) at different dose rates (1 and 6 Gy/min). For
      the eggs of different ages exposed to radiation, only the hatchability and pupal
      weight of 36-h-old eggs exposed to the dose rate of 1 Gy/min were not affected;
      therefore, 6 Gy/min was not suitable for irradiating eggs. The viability of the
      parents and progenies of D. longicaudata when the parents were reared from 36-h
      old eggs irradiated at nine different doses (0, 5, 10, 15, 20, 25, 30, 35, and 40
      Gy) under laboratory conditions were investigated. The emergence percentage, sex
      ratio, and longevity of parasitoids developed from irradiated eggs were similar
      to those reared from nonirradiated hosts. A significant increase in larva
      mortality was observed for the eggs irradiated at doses above 25 Gy, and no
      redundant adult flies emerged at doses above 15 Gy. Hence, for B. dorsalis eggs
      to be applied in the mass rearing of D. longicaudata, the age of 36 h and a dose
      of 20-25 Gy are the optimal parameters. The results reveal that hosts and
      parasitoids need not be separated, enabling a reduction in cost, labor, and time
      and resulting in an improved mass rearing procedure for D. longicaudata.

PMID- 29596603
TI  - A Declaration of Independence: Implicit Alcohol Associations Have Independent,
      not Interactive, Relationships with Alcohol Consumption and AUD Risk.
AB  - Aims: The current study aimed to test for potential interactive effects of three
      implicit alcohol-related associations (drinking identity, alcohol approach and
      alcohol excitement) in predicting concurrent and prospective alcohol consumption
      and risk of alcohol use disorders (AUDs) in two samples of the US undergraduate
      drinkers and non-drinkers. Short summary: We investigated the independent and
      interactive effects of three implicit associations on alcohol consumption and
      risk of AUD in two US undergraduate student samples. We found that implicit
      associations had independent but not interactive effects on concurrent and
      subsequent alcohol consumption and risk of AUD in two independent samples.
      Methods: Implicit drinking identity, alcohol approach and alcohol excitement
      associations were assessed in two US undergraduate student samples (Sample 1: N =
      300, 55% female; Sample 2: N = 506, 57% female). Alcohol consumption and risk of
      AUD were assessed at baseline (Samples 1 and 2) and 3 months later (Sample 2). We
      fit zero-inflated negative binomial models to test for independent and
      interactive effects of the three implicit associations on alcohol consumption and
      risk of AUD. Results: Although we found multiple, unique main effects for alcohol
      associations, we found minimal evidence of interactions between implicit alcohol
      related associations. There was no reliable evidence of interactions in models in
      predicting alcohol consumption or risk of AUD, concurrently or prospectively, in
      either sample. Conclusions: Contrary to expectations, results from both studies
      indicated that implicit alcohol-related associations in the US undergraduate
      samples generally have independent, not interactive, relationships with alcohol
      consumption and risk of AUD.

PMID- 29596604
TI  - A structurally conserved motif in gamma-herpesvirus uracil-DNA glycosylases
      elicits duplex nucleotide-flipping.
AB  - Efficient gamma-herpesvirus lytic phase replication requires a virally encoded
      UNG-type uracil-DNA glycosylase as a structural element of the viral replisome.
      Uniquely, gamma-herpesvirus UNGs carry a seven or eight residue insertion of
      variable sequence in the otherwise highly conserved minor-groove DNA binding
      loop. In Epstein-Barr Virus [HHV-4] UNG, this motif forms a disc-shaped loop
      structure of unclear significance. To ascertain the biological role of the loop
      insertion, we determined the crystal structure of Kaposi's sarcoma-associated
      herpesvirus [HHV-8] UNG (kUNG) in its product complex with a uracil-containing
      dsDNA, as well as two structures of kUNG in its apo state. We find the disc-like
      conformation is conserved, but only when the kUNG DNA-binding cleft is occupied.
      Surprisingly, kUNG uses this structure to flip the orphaned partner base of the
      substrate deoxyuridine out of the DNA duplex while retaining canonical UNG
      deoxyuridine-flipping and catalysis. The orphan base is stably posed in the DNA
      major groove which, due to DNA backbone manipulation by kUNG, is more open than
      in other UNG-dsDNA structures. Mutagenesis suggests a model in which the kUNG
      loop is pinned outside the DNA-binding cleft until DNA docking promotes rigid
      structuring of the loop and duplex nucleotide flipping, a novel observation for
      UNGs.

PMID- 29596605
TI  - Evaluation of voriconazole anti-Acanthamoeba polyphaga in vitro activity, rat
      cornea penetration and efficacy against experimental rat Acanthamoeba keratitis.
AB  - Background: Acanthamoeba keratitis (AK) is a sight-threatening infectious
      disease. Its effective and safe medical therapy remains highly debated. Recently,
      voriconazole, a monotriazole with noted in vitro activity against a large variety
      of fungi, has been successfully used both topically and systemically to treat
      human AK cases. Objectives: To measure anti-Acanthamoeba polyphaga in vitro
      activity, anti-rat AK efficiency and rat cornea penetration of eye-drop and oral
      voriconazole. Methods: A. polyphaga was maintained in axenic cultures. In vitro,
      amoebicidal and cysticidal activities of voriconazole were measured using an XTT
      assay. AK lesions of Sprague Dawley rats were scored from grade 0 to grade 3. For
      21 days, from day 7 post-infection, voriconazole (1% solution) eye drops were
      instilled or voriconazole was administered by gavage (60 mg/kg/day). After
      killing, superficial corneal epithelium scrapings were cultured and analysed by
      PCR, and eye-globe histology was performed. Cornea and plasma concentrations were
      determined using 2D HPLC separation and tandem MS. Results: In vitro,
      voriconazole inhibited trophozoite proliferation with an IC50 value of 0.02 mg/L
      and an IC90 value of 2.86 mg/L; no cysticidal effect was found. In AK rats, eye
      drops reduced clinical worsening from day 7 to day 14 post-infection and oral
      voriconazole was not effective. Voriconazole cornea concentrations were directly
      dependent on the frequency of eye-drop instillations, which resulted in lower
      plasma concentrations, whilst oral voriconazole resulted in lower cornea
      concentrations. Conclusions: Present data underline the need for high-frequency
      eye-drop instillation regimens for efficient AK therapy.

PMID- 29596606
TI  - Menopausal Hormone Therapy Is Associated With Reduced Total and Visceral
      Adiposity: The OsteoLaus Cohort.
AB  - Context: After menopause, fat mass (FM) and visceral adipose tissue (VAT)
      increase and nonbone lean body mass (LBM) decreases. Whether menopausal hormone
      therapy (MHT) reverses these changes remains controversial. Objective: To assess
      the effect of MHT on FM, VAT, and LBM before and after its withdrawal and
      evaluate potential confounders. Design: Cross-sectional study. Setting: General
      community. Patients or Other Participants: Women of the OsteoLaus cohort (50 to
      80 years old) who underwent dual-energy X-ray absorptiometry (DXA) with body
      composition assessment. After we excluded women with estrogen-modifying
      medications, the 1053 participants were categorized into current users (CUs),
      past users (PUs), and never users (NUs) of MHT. Intervention: None. Main Outcome
      Measures: VAT measured by DXA was the primary outcome. We assessed subtotal and
      android FM, LBM, muscle strength (hand grip), and confounding factors (caloric
      intake, physical activity, biomarkers). Results: The groups significantly
      differed in age, NU < CU < PU. Age-adjusted VAT was lower in CUs than NUs (P =
      0.03). CUs exhibited lower age-adjusted body mass index (BMI) (-0.9 kg/m2) and a
      trend for lower FM (-1.3 kg). The 10-year gain of VAT (P < 0.01) and subtotal and
      android FM (P < 0.05) was prevented in CUs. No difference in LBM or hand grip was
      detected. No residual effect was detected for PUs, including for early MHT
      discontinuers. The confounding factors did not significantly differ between
      groups except for higher caloric intake in PUs compared with NUs. Conclusions:
      MHT is associated with significantly decreased VAT, BMI, and android FM. No
      benefit is detected for LBM. The benefits are not preserved in PUs, suggesting
      caution when MHT is discontinued.

PMID- 29596607
TI  - Workplace Respiratory Protection Factors during Asbestos Removal Operations.
AB  - Numerous changes have been made to the French labour regulations in recent years
      relating to the prevention of risks of exposure to asbestos fibres for operators
      removing asbestos-containing materials. These changes refer to the method used to
      count fibres, the collective and personal protective devices to be used on these
      worksites, and the occupational exposure limit value, which was reduced to 10 f.L
      1 on 2 July 2015. In this context, this study assessed the level of respiratory
      protection afforded by supplied-air respirators and powered air-purifying
      respirators by monitoring exposure for several operators on nine worksites. The
      levels of dustiness measured in personal samples taken outside masks showed
      significant evidence of potential exposure during removal of asbestos-containing
      plaster or sprayed asbestos, and when using abrasive blasting to treat asbestos
      containing materials. For these tasks outside concentration regularly exceeds
      25000 f.L-1. Measurements inside masks were generally low, under 10 f.L-1, except
      in some situations involving the removal of asbestos-containing plaster. This
      partial penetration of fibres inside masks could be due to the high loading
      linked to this material. The distributions of Workplace Protection Factors
      obtained for the two types of respiratory protective devices studied were broad,
      and the fifth percentile values equal to 236 and 104, respectively, for supplied
      air respirators and powered air-purifying respirators. This work highlights once
      again the need to prioritize collective protection when seeking to prevent
      asbestos-related risks.

PMID- 29596608
TI  - SimPhospho: a software tool enabling confident phosphosite assignment.
AB  - Motivation: Mass spectrometry combined with enrichment strategies for
      phosphorylated peptides has been successfully employed for two decades to
      identify sites of phosphorylation. However, unambiguous phosphosite assignment is
      considered challenging. Given that site-specific phosphorylation events function
      as different molecular switches, validation of phosphorylation sites is of utmost
      importance. In our earlier study we developed a method based on simulated
      phosphopeptide spectral libraries, which enables highly sensitive and accurate
      phosphosite assignments. To promote more widespread use of this method, we here
      introduce a software implementation with improved usability and performance.
      Results: We present SimPhospho, a fast and user-friendly tool for accurate
      simulation of phosphopeptide tandem mass spectra. Simulated phosphopeptide
      spectral libraries are used to validate and supplement database search results,
      with a goal to improve reliable phosphoproteome identification and reporting. The
      presented program can be easily used together with the Trans-Proteomic Pipeline
      and integrated in a phosphoproteomics data analysis workflow. Availability and
      implementation: SimPhospho is open source and it is available for Windows, Linux
      and Mac operating systems. The software and its user's manual with detailed
      description of data analysis as well as test data can be found at
      https://sourceforge.net/projects/simphospho/. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29596609
TI  - From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the
      Breast by Comparing Take Rate, Quality, and Longevity.
AB  - Background: Autologous fat grafting (AFG) to the breast is a frequent procedure
      in aesthetic and reconstructive surgery. Despite pure volume gain, questions
      remain regarding the engraftment rate, quality, and longevity. Little is known
      about the role of recipient tissue or innervation of the grafted area.
      Objectives: The goal of this study was to determine the optimal recipient layer
      and muscular pretreatment of AFG. Methods: Fat was grafted to the breast,
      pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment
      included excision of a nerve segment, botulinum toxin (BTX) injection, or no
      treatment. Magnetic resonance imaging (MRI) and histological workup were carried
      out after 2 and 6 weeks. Results: Six weeks after AFG, the proportion of viable
      fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]).
      The signs of inflammation decreased over time. Intramuscular grafting with intact
      nerves had a decreasing effect on the viability of the grafted cells compared
      with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]).
      Conclusions: If utilized on an intact nerve, intramuscular injection may lead to
      inferior results. If the nerve was cut or treated with BTX; however,
      intramuscular injection tends to be superior. These findings may prove
      interesting for future studies and eventual clinical application.

PMID- 29596610
TI  - Multiple coronary artery fistulae in a young man.

PMID- 29596611
TI  - Comparison of Frankliniella fusca and Frankliniella occidentalis (Thysanoptera:
      Thripidae) as Vectors for a Peanut Strain of Tomato Spotted Wilt Orthotospovirus.
AB  - Tomato spotted wilt orthotospovirus (TSWV) is a major disease in peanut, Arachis
      hypogaea L., across peanut producing regions of the United States and elsewhere.
      Two thrips, Frankliniella fusca Hinds and Frankliniella occidentalis Pergande
      (Thysanoptera: Thripidae), are considered important vectors of TSWV in peanut in
      the Southeast. We compared the efficiency of acquisition (by larvae) and
      transmission (adults) of both thrips species for TSWV (Texas peanut-strain) to
      leaf disks of peanut (Florunner), as well as to Impatiens walleriana Hook. f.
      (Dwarf White Baby) and Petunia hybrida Juss. 'Fire Chief' using double antibody
      sandwich enzyme-linked immunosorbent assay (DAS-ELISA). Both species were
      competent TSWV vectors in peanut and Impatiens, although F. fusca was the more
      efficient vector overall, i.e., virus acquisition and transmission rates for F.
      fusca averaged over several bioassays were 51.7 and 26.6%, respectively, compared
      with 20.0 and 15.3% for F. occidentalis. Neither species effectively transmitted
      this TSWV strain to Petunia (i.e., <=3.6% transmission). We found statistically
      similar virus acquisition and transmission rates between both sexes for each
      species. We also detected no differences in TSWV-acquisition and transmission
      frequency between macropterous and brachypterous (short-wing) forms of F. fusca
      collected from a field population in south Texas. DAS-ELISA failed to detect low
      levels of TSWV in a few thrips that subsequently proved to be competent vectors.

PMID- 29596613
TI  - Repeat left ventricular assist device exchange with inflow or outflow correction
      for recurrent pump thrombosis and cerebral haemorrhage through limited incisions.
AB  - Left ventricular assist devices (LVADs) may require subsequent pump exchange due
      to device thrombosis or thromboembolism. A limited left thoracotomy may offer
      advantages over standard full sternotomy in redo procedures by preserving
      pristine median access and decreasing the potential for re-entry injuries,
      postoperative bleeding and transfusion requirements. We describe repeat LVAD
      exchange via the left limited thoracotomy with outflow graft anastomosis to the
      left subclavian artery with the correction of LVAD inflow cannula angulation
      following recurrent LVAD thromboses.

PMID- 29596612
TI  - Burn Injury May Have Age-Dependent Effects on Strength and Aerobic Exercise
      Capacity in Males.
AB  - Whether burn injury affects boys and men differently is currently unknown. To
      test the hypothesis that burned boys have lower exercise capacity and exercise
      training-induced responses compared with burned men, 40 young boys (12 +/- 4
      years, 149 +/- 20 cm, 46 +/- 18 kg) were matched to 35 adult men (33 +/- 9 years,
      174 +/- 10 cm, 84 +/- 16 kg) based on extent of burn injury (total body surface
      area burned, boys 46 +/- 14% vs men 47 +/- 30, P = .85) and length of hospital
      stay (boys 33 +/- 23 vs men 41 +/- 32 days, P = .23). Strength (peak torque) and
      cardiorespiratory fitness (peak VO2) were normalized to kg of lean body mass for
      group comparisons. Each group was also compared with normative age-sex matched
      values at discharge and after an aerobic and resistance exercise training (RET)
      program. A two-way factorial analysis of covariance assessed interaction and main
      effects of group and time. We found that boys and men showed similar pre-RET to
      post-RET increases in total lean (~4%) and fat (7%) mass (each P <= .008). Both
      groups had lower age-sex matched norm values at discharge for peak torque (boys
      36%; men 51% of normative values) and peak VO2 (boys: 44; men: 59%; each P <=
      .0001). Boys strength were 13-15 per cent lower than men at discharge and after
      RET (main effect for group, P < .0001). Cardiorespiratory fitness improved to a
      greater extent in men (19%) compared with boys (10%) after the RET (group * time
      interaction, P = .011). These results show that at discharge and after RET, burn
      injury may have age-dependent effects and should be considered when evaluating
      efficacy and progress of the exercise program.

PMID- 29596614
TI  - Trials and tribulations: cross-learning from the practices of epidemiologists and
      economists in the evaluation of public health interventions.
AB  - The randomized controlled trial is commonly used by both epidemiologists and
      economists to test the effectiveness of public health interventions. Yet we have
      noticed differences in practice between the two disciplines. In this article, we
      propose that there are some underlying differences between the disciplines in the
      way trials are used, how they are conducted and how results from trials are
      reported and disseminated. We hypothesize that evidence-based public health could
      be strengthened by understanding these differences, harvesting best-practice
      across the disciplines and breaking down communication barriers between
      economists and epidemiologists who conduct trials of public health interventions.

PMID- 29596615
TI  - ONETOOL for the analysis of family-based big data.
AB  - Motivation: Despite the need for separate tools to analyze family-based data,
      there are only a handful of tools optimized for family-based big data compared to
      the number of tools available for analyzing population-based data. Results:
      ONETOOL implements the properties of well-known existing family data analysis
      tools and recently developed methods in a computationally efficient manner, and
      so is suitable for analyzing the vast amount of variant data available from
      sequencing family members, providing a rich choice of analysis methods for big
      data on families. Availability and implementation: ONETOOL is freely available
      from http://healthstat.snu.ac.kr/software/onetool/. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29596616
TI  - VEGF and VEGFB Play Balancing Roles in Adipose Differentiation, Gene Expression,
      and Function.
AB  - Obesity is the result of abnormal adipose development and energy metabolism.
      Using vascular endothelial growth factor (VEGF) B-knockout and inducible VEGF
      downregulation mouse models, we have shown that VEGFB inactivation caused
      expansion of white adipose, whitening of brown adipose, an increase in fat
      accumulation, and a reduction in energy consumption. At the same time, expression
      of the white adipose-associated genes was increased and brown adipose-associated
      genes decreased. VEGF repression, in contrast, induced brown adipose expansion
      and brown adipocyte development in white adipose, increased energy expenditure,
      upregulated brown adipose-associated genes, and downregulated white adipose
      associated genes. When VEGFB-knockout and VEGF-repressed mice are crossed
      together, VEGF and VEGFB can counteractively regulate large numbers of genes and
      efficiently reverse each other's roles. These genes, under counteractive VEGF and
      VEGFB regulations, include transcription factors, adhesion molecules, and
      metabolic enzymes. This balancing role is confirmed by morphologic and functional
      changes. This study reports that VEGF and VEGFB counteractively regulate adipose
      development and function in energy metabolism.

PMID- 29596617
TI  - Association of Trajectories of Higher-Level Functional Capacity with Mortality
      and Medical and Long-Term Care Costs Among Community-Dwelling Older Japanese.
AB  - Background: Higher-level functional capacity is crucial component for independent
      living in later life. We used repeated-measures analysis to identify aging
      trajectories in higher-level functional capacity. We then determined whether
      these trajectories were associated with all-cause mortality and examined
      differences in medical and long-term care costs between trajectories among
      community-dwelling older Japanese. Methods: 2,675 adults aged 65-90 years
      participated in annual geriatric health assessments and biennial health
      monitoring surveys during the period from October 2001 through August 2011. The
      average number of follow-up assessments was 4.0, and the total number of
      observations was 10,609. Higher-level functional capacity, which correspond to
      the fourth and fifth sublevels of Lawton's hierarchical model, was assessed with
      the Tokyo Metropolitan Institute of Gerontology-Index of Competence (TMIG-IC).
      Results: We identified four distinct trajectory patterns (high-stable, late-onset
      decreasing, early-onset decreasing, and low-decreasing) on the TMIG-IC through
      age 65-90 years. As compared with the high-stable trajectory group, participants
      in the late-onset decreasing, early-onset decreasing, and low-decreasing TMIG-IC
      trajectory groups had adjusted hazard ratios for mortality of 1.22 (95%
      confidence interval: 1.01-1.47), 1.90 (1.53-2.36), and 2.87 (2.14-3.84),
      respectively. Participants with high-stable and late-onset decreasing higher
      level functional capacity trajectories had lower mean monthly medical costs and
      long-term care costs. In contrast, mean total costs were higher for those with
      low-decreasing trajectories, after excluding the large increase in such costs at
      the end of life. Conclusions: People with a low-decreasing aging trajectory in
      higher-level functional capacity had higher risks of death and had high monthly
      total costs.

PMID- 29596619
TI  - Derailing individualized ovarian stimulation.

PMID- 29596618
TI  - Patterns in Health Care Access and Affordability Among Cancer Survivors During
      Implementation of the Affordable Care Act.
AB  - Importance: Cancer survivors face ongoing health issues and need access to
      affordable health care, yet studies examining health care access and
      affordability in this population are lacking. Objectives: To evaluate health care
      access and affordability in a national sample of cancer survivors compared with
      adults without cancer and to evaluate temporal trends during implementation of
      the Affordable Care Act. Design, Setting, and Participants: We used data from the
      National Health Interview Survey from 2010 through 2016 to conduct a population
      based study of 30 364 participants aged 18 years or older. We grouped
      participants as cancer survivors (n = 15 182) and those with no reported history
      of cancer, whom we refer to as control respondents (n = 15 182), matched on age.
      We excluded individuals reporting a cancer diagnosis prior to age 18 years and
      those with nonmelanoma skin cancers. Main Outcomes and Measures: We compared
      issues with health care access (eg, delayed or forgone care) and affordability
      (eg, unable to afford medications or health care services) between cancer
      survivors and control respondents. We also explored trends over time in the
      proportion of cancer survivors reporting these difficulties. Results: Of the 30
      364 participants, 18 356 (57.4%) were women. The mean (SD) age was 63.5 (23.5)
      years. Cancer survivors were more likely to be insured (14 412 [94.8%] vs 13 978
      [92.2%], P < .001) and to have government-sponsored insurance (7266 [44.3%] vs
      6513 [38.8%], P < .001) compared with control respondents. In multivariable
      models, cancer survivors were more likely than control respondents to report
      delayed care (odds ratio [OR], 1.38; 95% CI, 1.16-1.63), forgone medical care
      (OR, 1.76; 95% CI, 1.45-2.12), and/or inability to afford medications (OR, 1.77;
      95% CI, 1.46-2.14) and health care services (OR, 1.46; 95% CI, 1.27-1.68) (P <
      .001 for all). From 2010 to 2016, the proportion of survivors reporting delayed
      medical care decreased each year (B = 0.47; P = .047), and the proportion of
      those needing and not getting medical care also decreased each year (B = 0.35; P
      = .04). In addition, the proportion of cancer survivors who reported being unable
      to afford prescription medication decreased each year (B=0.66; P = .004) and the
      proportion of those unable to afford at least 1 of 6 services decreased each year
      (B = 0.51; P = .01). Conclusions and Relevance: Despite higher rates of insurance
      coverage, cancer survivors reported greater difficulties accessing and affording
      health care compared with adults without cancer. Importantly, the proportion of
      survivors reporting these issues continued a downward trend throughout our
      observation period in the years following the implementation of the Affordable
      Care Act. Our findings suggest incremental improvement in health care access and
      affordability after recent health care reform and provide an important benchmark
      as additional changes are likely to occur in the coming years.

PMID- 29596621
TI  - A decade of ChIP-seq.

PMID- 29596620
TI  - Biofilm growth and control in cooling water industrial systems.
AB  - Matrix-embedded, surface-attached microbial communities, known as biofilms,
      profusely colonise industrial cooling water systems, where the availability of
      nutrients and organic matter favours rapid microbial proliferation and their
      adhesion to surfaces in the evaporative fill material, heat exchangers, water
      reservoir and cooling water sections and pipelines. The extensive growth of
      biofilms can promote micro-biofouling and microbially induced corrosion (MIC) as
      well as pose health problems associated with the presence of pathogens like
      Legionella pneumophila. This review examines critically biofilm occurrence in
      cooling water systems and the main factors potentially affecting biofilm growth,
      biodiversity and structure. A broad evaluation of the most relevant biofilm
      monitoring and control strategies currently used or potentially useful in cooling
      water systems is also provided.

PMID- 29596622
TI  - On the Difficulties of Studying Pain Management in Individuals with Developmental
      Delay-Response.

PMID- 29596623
TI  - So Close and Yet So Irritating: Negative Relations and Implications for Well
      being by Age and Closeness.
AB  - Objectives: Negative social relationships are associated with poor health,
      chronic illness, and mortality. Yet, we know little about the dynamics of
      negative aspects of relationships within individual's closest relationships over
      time, how those experiences vary by age, and the implications of those
      relationships for well-being. Method: A total of 592 participants (ages 25 to 97;
      M= 57.5; 63.3% women) from the Social Relations Study completed monthly web
      surveys for up to 12 months. Each month they reported negative relationship
      quality with their three closest network members and multiple dimensions of well
      being (positive affect, negative affect, self-rated health, and sleep quality).
      Results: Multilevel models revealed older individuals reported less negativity in
      their relationships than younger people, but fewer age differences in the closest
      tie. Greater negative relationship quality predicted poor well-being (i.e.,
      greater negative affect, sleep problems). Links between negative relations and
      well-being were less strong among older individuals; especially in the closest
      ties. Discussion: Results were partially consistent with the strength and
      vulnerability integration (SAVI) model, which proposes fewer age-related
      improvements in emotion regulation when individuals are unable to avoid tensions.
      Despite feeling just as negative as younger individuals, older individuals may be
      more resilient to tensions in their closest relationships.

PMID- 29596624
TI  - The Potential of Autologous Fat Transfer as a Valuable Tool for Cosmetic and
      Reconstructive Purposes: Acknowledged Risks, Limitations, and Benefits.

PMID- 29596625
TI  - Can we address cancer disparities in immigrants by improving cancer literacy
      through English as a second language instruction?
AB  - In many Western countries, immigrants exhibit disparities in cancer incidence and
      mortality, and variable uptake of cancer prevention services. New immigrants may
      not be aware of cancer risks pertinent to their new country, or prevention
      resources. Traditional cancer prevention health messaging may not be accessible
      for cultural, language, or literacy reasons. New methods are needed. In North
      America, health message delivery via English classes for immigrants is showing
      potential as an efficacious and a feasible way to reach immigrants at the same
      time improving language skills. Interventions published to date are promising but
      limited in their ability to generalize or be adapted to a variety of populations
      and settings. This concept paper aims to synthesize previous findings and
      identify ways to improve and advance the translation potential of this approach.
      We propose that this could be achieved by (i) using a translation framework to
      guide intervention planning, development, implementation, and evaluation; (ii)
      encouraging and evaluating health message spread throughout language learners'
      social networks; and (iii) incorporating cultural sensitivity into the
      curriculum. A pilot project following these recommendations is planned for
      Australia and will be discussed. These recommendations could serve as a framework
      to fit the requirements of immigrant language programs in other countries and
      other health topics.

PMID- 29596626
TI  - Individualized FSH dosing improves safety and reduces iatrogenic poor response
      while maintaining live-birth rates.

PMID- 29596627
TI  - A Putative Insulin-like Androgenic Gland Hormone Receptor Gene Specifically
      Expressed in Male Chinese Shrimp.
AB  - The insulin-like androgenic gland hormone (IAG) is the key regulator in
      crustacean male sexual differentiation. As a secreted peptide hormone, IAG might
      perform its biological function through interacting with the membrane receptor.
      However, the receptor of IAG remains unclear. In the current study, a putative
      IAG receptor gene (FcIAGR) was identified in Fenneropenaeus chinensis. The
      deduced amino acid sequence of FcIAGR contained several conserved domains of
      insulin-like receptor proteins, including two L domains (L1 and L2), a cysteine
      rich domain, three fibronectin III domains, a transmembrane domain, and an
      intracellular tyrosine kinase domain. Tissue distribution and in situ
      hybridization analysis showed that FcIAGR was predominantly expressed in the
      androgenic gland and testis in male F. chinensis. Protein colocalization analysis
      in HEK293 cells showed that FcIAGR could colocalize with both FcIAG1 and FcIAG2,
      respectively. Yeast two-hybrid assay further confirmed the interactions between
      FcIAGR and FcIAGs. After a long-term silencing of FcIAGR with double-stranded
      RNA, most of the germ cells in the testis were arrested at the secondary
      spermatocytes, whereas those in the control developed into sperm cells. The data
      indicated that FcIAGR was the receptor of FcIAGs in F. chinensis. The current
      study provides insight into the mechanism that the insulin-like signaling pathway
      regulates the male sexual differentiation in Decapoda crustaceans.

PMID- 29596628
TI  - The quantitative models for broiler chicken response to monochromatic, combined,
      and mixed light-emitting diode light: A meta-analysis.
AB  - Although many experiments have been conducted to clarify the response of broiler
      chickens to light-emitting diode (LED) light, those published results do not
      provide a solid scientific basis for quantifying the response of broiler
      chickens. This study used a meta-analysis to establish light spectral models of
      broiler chickens. The results indicated that 455 to 495 nm blue LED light
      produced the greatest positive response in body weight by 10.66% (BW; P < 0.001)
      and 515 to 560 nm green LED light increased BW by 6.27% (P < 0.001) when compared
      with white light. Regression showed that the wavelength (455 to 660 nm) was
      negatively related to BW change of birds, with a decrease of about 4.9% BW for
      each 100 nm increase in wavelength (P = 0.002). Further analysis suggested that a
      combination of the two beneficial light sources caused a synergistic effect. BW
      was further increased in birds transferred either from green LED light to blue
      LED light (17.23%; P < 0.001) or from blue LED light to green LED light (17.52%;
      P < 0.001). Moreover, birds raised with a mixture of green and blue LED light
      showed a greater BW promotion (10.66%; P < 0.001) than those raised with green
      LED light (6.27%). A subgroup analysis indicated that BW response to
      monochromatic LED light was significant regardless of the genetic strain, sex,
      control light sources, light intensity and regime of LED light, environmental
      temperature, and dietary ME and CP (P > 0.05). However, there was an interaction
      between the FCR response to monochromatic LED light with those covariant factors
      (P < 0.05). Additionally, green and yellow LED light played a role in affecting
      the meat color, quality, and nutrition of broiler chickens. The results indicate
      that the optimal ratio of green * blue of mixed LED light or shift to green-blue
      of combined LED light may produce the optimized production performance, whereas
      the optimal ratio of green/yellow of mixed or combined LED light may result in
      the optimized meat quality.

PMID- 29596629
TI  - Authors' reply to commentary: Renewed controversy over cardiovascular risk with
      non-steroidal anti-inflammatory drugs.

PMID- 29596630
TI  - Atrial fibrillation ablation alone or atrial fibrillation ablation plus an
      antiarrhythmic drug?

PMID- 29596631
TI  - Making point mutations in Escherichia coli BL21 genome using the CRISPR-Cas9
      system.
AB  - The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR
      associated protein 9 (Cas9) system is an efficient and rapid tool for genome
      editing. However, its utilization in bacteria suffers challenges such as the risk
      of repeated recognition and cutting by Cas9. Here we established a two-step
      genome editing strategy using the Streptococcus pyogenes CRISPR-Cas9 system to
      achieve a clean mutation with only the target sites into the Escherichia coli
      genome. This strategy can avoid the risk of repeated cutting by guide RNA
      (gRNA)/Cas9 without altering the protospacer-adjacent motif or inserting
      additional silent mutations into the genome. The principles and approaches we
      developed in this study can be applied to modify coding and non-coding sequences
      in essential and non-essential genes and can also be used for precise genome
      editing in other microorganisms.

PMID- 29596632
TI  - Usefulness of individualized FSH, LH and GH dosing in ovarian stimulation of
      women with low ovarian reserve.

PMID- 29596633
TI  - OpenNotes in oncology: oncologists' perceptions and a baseline of the content and
      style of their clinician notes.
AB  - Patients' ability to access their provider's clinical notes (OpenNotes) has been
      well received and has led to greater transparency in health systems. However, the
      majority of this research has occurred in primary care, and little is known about
      how patients' access to notes is used in oncology. This study aims to understand
      oncologists' perceptions of OpenNotes, while also establishing a baseline of the
      linguistic characteristics and patterns used in notes.Data from 13 in-depth,
      semistructured interviews with oncologists were thematically analyzed. In
      addition, the Linguistic Inquiry and Word Count (LIWC) program evaluated over 200
      clinician notes, measuring variables encompassing emotions, thinking styles,
      social concerns, and parts of speech. Analysis from LIWC revealed that notes
      contained negative emotional tone, low authenticity, high clout, and high
      analytical writing. Oncologists' use of stigmatized and sensitive words, such as
      "obese" and "distress," was mainly absent. Themes from interviews revealed that
      oncologists were uncertain about patients' access to their notes and may edit
      their notes to avoid problematic terminology. Despite their reluctance to embrace
      OpenNotes, they envisioned opportunities for an improved patient-provider
      relationship due to patients initiating interactions from viewing
      notes.Oncologists believe notes are not intended for patients and altering their
      content may compromise the integrity of the note. This study established a
      baseline for further study to compare notes pre-implementation to post
      implementation. Further analysis will clarify whether oncologists are altering
      the style and content of their notes and determine the presence of patient
      centered language.

PMID- 29596634
TI  - Expression and purification of biologically active recombinant rabbit monocyte
      chemoattractant protein1 in Escherichia coli.
AB  - Monocyte chemoattractant protein 1 (MCP1) with recruiting monocytes is an
      important factor at the beginning of inflammatory disorders such as
      atherosclerosis which seems its blocking preclude this process and help
      improvement of related diseases. To perform clinical research in this field, MCP1
      protein is required but firstly, animal studies should be done. As the rabbit is
      a suitable model for many inflammatory disorders, and Escherichia coli BL21(DE3)
      (BL21) cell is a high-efficiency host for protein expression, we decided to
      produce recombinant rabbit MCP1 (rRMCP1) in BL21/pET28a system. After codon
      usage, a construct containing RMCP1 sequence was synthesized, cloned into the
      pET28a plasmid, and overexpressed in BL21 cells. Followed that, with changing
      expression condition such as cell concentration before the induction, time
      period, temperature, shaking rate and inducer concentration (IPTG), rRMCP1
      expression was optimized, and purified by Ni-NTA. The biological activity of the
      expressed protein was verified using monocyte migration assay. Using this
      expression system, nearly 28 mg/mL rRMCP1 was produced at 26 degrees C/180 rpm
      for 24 h in LB broth medium with 1 mM IPTG. Therefore, we were succeeded to
      express the intermediate level of rRMCP1 with this method. This amount of protein
      is sufficient for biological researches in the laboratory.

PMID- 29596636
TI  - Cluster randomized trials with a small number of clusters: which analyses should
      be used?

PMID- 29596635
TI  - Tiny architects: biogenesis of intracellular replicative niches by bacterial
      pathogens.
AB  - Co-evolution of bacterial pathogens with their hosts led to the emergence of a
      stunning variety of strategies aiming at the evasion of host defences,
      colonisation of host cells and tissues and, ultimately, the establishment of a
      successful infection. Pathogenic bacteria are typically classified as
      extracellular and intracellular; however, intracellular lifestyle comes in many
      different flavours: some microbes rapidly escape to the cytosol whereas other
      microbes remain within vacuolar compartments and harness membrane trafficking
      pathways to generate their host-derived, pathogen-specific replicative niche.
      Here we review the current knowledge on a variety of vacuolar lifestyles, the
      effector proteins used by bacteria as tools to take control of the host cell and
      the main membrane trafficking signalling pathways targeted by vacuolar pathogens
      as source of membranes and nutrients. Finally, we will also discuss how host
      cells have developed countermeasures to sense the biogenesis of the aberrant
      organelles harbouring bacteria. Understanding the dialogue between bacterial and
      eukaryotic proteins is the key to unravel the molecular mechanisms of infection
      and in turn, this may lead to the identification of new targets for the
      development of new antimicrobials.

PMID- 29596637
TI  - Improving the capacity for learning and improvement in health care.

PMID- 29596638
TI  - The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a
      series of 486 cases from the Eurofever international registry.
AB  - Objectives: Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent
      multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by
      sterile bone osteolytic lesions. The aim of this study was to evaluate the
      demographic data and clinical, instrumental and therapeutic features at baseline
      in a large series of CNO/CRMO patients enrolled in the Eurofever registry.
      Methods: A web-based registry collected retrospective data on patients affected
      by CRMO/CNO. Both paediatric and adult centres were involved. Results: Complete
      baseline information on 486 patients was available (176 male, 310 female). The
      mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in
      31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1
      year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing
      a mean number of 4.1 lesions. More frequent manifestations not directly related
      to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5%
      palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial
      rash) and gastrointestinal symptoms (8%). A total of 361 patients have been
      treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with
      MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response.
      Conclusion: This is the largest reported case series of CNO patients, showing
      that the range of associated clinical manifestations is rather heterogeneous. The
      study confirms that the disease usually presents with an early teenage onset, but
      it may also occur in adults, even in the absence of mucocutaneous manifestations.

PMID- 29596639
TI  - The BODY-Q Stretch Marks Scale: A Development and Validation Study.
AB  - Background: Stretch marks are common permanent dermal lesions that can cause
      psychosocial distress. A number of treatment modalities are available, with the
      majority targeted towards collagen production. Objectives: To develop and field
      test a new BODY-Q scale to measure appearance of stretch marks in order to
      provide a means to incorporate the patient perspective into future treatment
      studies. Methods: We previously described the development of the BODY-Q
      conceptual framework, which involved a literature review, 63 patient interviews,
      22 cognitive interviews and input from 9 experts, and the international field
      test study that involved 403 weight loss and 331 body contouring patients. To
      develop the Stretch Marks scale, we reexamined appearance codes from the original
      interviews. The scale was field tested in an international study. Rasch
      measurement theory (RMT) analysis was used to refine the scale and examine
      measurement properties. Results: The Stretch Marks scale was completed by 630
      participants, who provided 774 assessments. After dropping 3 items, the data fit
      the Rasch model (P = 0.56). Items (eg, length, width, amount, location, up close)
      mapped out a well-targeted clinical hierarchy. All items had ordered thresholds
      and good item fit. There was no evidence of differential item functioning (bias)
      by gender, age group or language (English vs Danish). The scale evidenced high
      reliability (ie, person separation index = 0.94, Cronbach's alpha = 0.97). For
      construct validity, the mean score correlated with the total number of body areas
      with stretch marks, higher BMI before bariatric surgery, and other BODY-Q scales.
      Conclusions: This scale could be used to measure the impact of innovative
      treatments for stretch marks. Level of Evidence 4: 

PMID- 29596640
TI  - Multiple Factors Confounding Phylogenetic Detection of Selection on Codon Usage.
AB  - Detecting selection on codon usage (CU) is a difficult task, since CU can be
      shaped by both the mutational process and selective constraints operating at the
      DNA, RNA, and protein levels. Yang and Nielsen (2008) developed a test (which we
      call CUYN) for detecting selection on CU using two competing mutation-selection
      models of codon substitution. The null model assumes that CU is determined by the
      mutation bias alone, whereas the alternative model assumes that both mutation
      bias and/or selection act on CU. In applications on mammalian-scale alignments,
      the CUYN test detects selection on CU for numerous genes. This is surprising,
      given the small effective population size of mammals, and prompted us to use
      simulations to evaluate the robustness of the test to model violations.
      Simulations using a modest level of CpG hypermutability completely mislead the
      test, with 100% false positives. Surprisingly, a high level of false positives
      (56.1%) resulted simply from using the HKY mutation-level parameterization within
      the CUYN test on simulations conducted with a GTR mutation-level
      parameterization. Finally, by using a crude optimization procedure on a parameter
      controlling the CpG hypermutability rate, we find that this mutational property
      could explain a very large part of the observed mammalian CU. Altogether, our
      work emphasizes the need to evaluate the potential impact of model violations on
      statistical tests in the field of molecular phylogenetic analysis. The source
      code of the simulator and the mammalian genes used are available as a GitHub
      repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).

PMID- 29596641
TI  - Primed CRISPR adaptation in Escherichia coli cells does not depend on
      conformational changes in the Cascade effector complex detected in Vitro.
AB  - In type I CRISPR-Cas systems, primed adaptation of new spacers into CRISPR arrays
      occurs when the effector Cascade-crRNA complex recognizes imperfectly matched
      targets that are not subject to efficient CRISPR interference. Thus, primed
      adaptation allows cells to acquire additional protection against mobile genetic
      elements that managed to escape interference. Biochemical and biophysical studies
      suggested that Cascade-crRNA complexes formed on fully matching targets (subject
      to efficient interference) and on partially mismatched targets that promote
      primed adaption are structurally different. Here, we probed Escherichia coli
      Cascade-crRNA complexes bound to matched and mismatched DNA targets using a
      magnetic tweezers assay. Significant differences in complex stabilities were
      observed consistent with the presence of at least two distinct conformations.
      Surprisingly, in vivo analysis demonstrated that all mismatched targets
      stimulated robust primed adaptation irrespective of conformational states
      observed in vitro. Our results suggest that primed adaptation is a direct
      consequence of a reduced interference efficiency and/or rate and is not a
      consequence of distinct effector complex conformations on target DNA.

PMID- 29596643
TI  - Supercharging Extra-Large Anterolateral Thigh Flaps for Single-Stage Resurfacing
      of Massive Burn Defects Over Upper Extremity Elbow Joints.
AB  - The resurfacing of soft tissue over extensor side of elbow joint after a full
      thickness burn injury is challenging due to greater amount of soft tissue needed.
      Local or regional flaps in the upper limb are not readily available and the use
      of free flap is the consensus. We want to present the first report of an extra
      large anterolateral thigh (ALT) flap for a 1-stage coverage of an extensive elbow
      defect. The versatility of the ALT flap in design offers the surgeon the added
      option of supercharging the flap for increased survival when using a large flap
      for extensive wound coverage in the elbow. A 36-year-old male was admitted due to
      full thickness contact thermal burn over extensor side of left elbow. After
      debridement, we applied a 1-stage reconstruction with an extra-large ALT flap for
      the wound coverage and a supercharging design was made for the better perfusion
      for the flap. The flap was well perfused and the patient was discharged under
      stable wound condition as well as a fair functional outcome. The ALT flap is
      ideal for resurfacing large defects over the elbow and its anatomy and multiple
      source perforators allow the use of supercharging to enhance flap survival in the
      upper limb.

PMID- 29596642
TI  - The DNA damage response activates HPV16 late gene expression at the level of RNA
      processing.
AB  - We show that the alkylating cancer drug melphalan activated the DNA damage
      response and induced human papillomavirus type 16 (HPV16) late gene expression in
      an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression
      included inhibition of the HPV16 early polyadenylation signal that resulted in
      read-through into the late region of HPV16. This was followed by activation of
      the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of
      spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased
      association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA,
      and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16
      mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and
      enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.

PMID- 29596644
TI  - A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water,
      Sanitation, and Handwashing Intervention in Rural Bangladesh.
AB  - Water, sanitation, and handwashing interventions may confer spillover effects on
      neighbors of intervention recipients by interrupting pathogen transmission. We
      measured geographically local spillovers in WASH Benefits, a cluster-randomized
      trial in rural Bangladesh, by comparing outcomes among neighbors of intervention
      vs. control participants. WASH Benefits randomly allocated geographically-defined
      clusters to a compound-level intervention (chlorinated drinking water, upgraded
      sanitation, and handwashing promotion) or control. From January to August 2015,
      in 180 clusters, we enrolled 1,799 neighboring children age-matched to trial
      participants that would have been eligible for WASH Benefits had they been
      conceived slightly earlier or later. After 28 months of intervention, we
      quantified fecal indicator bacteria in toy rinse and drinking water samples,
      measured soil-transmitted helminth infections, and recorded caregiver-reported
      diarrhea and respiratory illness. Neighbors' characteristics were balanced across
      arms. The prevalence of detectable E. coli in tubewell samples was lower for
      neighbors of intervention vs. control trial participants (prevalence ratio =
      0.83; 0.73, 0.95). There was no difference in fecal indicator bacteria prevalence
      between arms for other environmental samples. Prevalence was similar in neighbors
      of intervention vs. control participants for soil-transmitted helminth infection,
      diarrhea, and respiratory illness. A compound-level water, sanitation, and
      handwashing intervention reduced neighbors' tubewell water contamination but did
      not impact neighboring children's health.

PMID- 29596645
TI  - Combined Use of Predatory Mirids With Amblyseius swirskii (Acari: Phytoseiidae)
      to Enhance Pest Management in Sweet Pepper.
AB  - The combined release of Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) with
      Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae) provides effective
      control of sweet pepper key pests, such as thrips and whiteflies. However, the
      management of the aphids can still be improved. Recently, the predatory mirids
      Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae) and Macrolophus pygmaeus
      (Rambur) (Hemiptera: Miridae) have been found to be effective in the control of
      aphids, thrips and whiteflies when tested alone. Hence, integrating one of these
      two mirids with A. swirskii might enhance sweet pepper pest management. In this
      work, we began by investigating the co-occurrence of both mirid species when
      released together with A. swirskii. This was compared to the standard release of
      O. laevigatus with A. swirskii. N. tenuis and A. swirskii were involved in a
      bidirectional intraguild predation (IGP). On the contrary, this interaction (IGP)
      was apparently unidirectional in the case of M. pygmaeus with A. swirskii and O.
      laevigatus with A. swirskii. Both, M. pygmaeus and O. laevigatus significantly
      reduced the abundance of A. swirskii. Secondly, in a greenhouse experiment, where
      the same release combinations were tested (either N. tenuis, M. pygmaeus or O.
      laevigatus combined with A. swirskii), IGP seemed to be neutralized. Mirids with
      A. swirskii significantly suppressed thrips, whitefly, and aphid infestations.
      Contrarily, the combined use of O. laevigatus with A. swirskii did not reached a
      satisfactory control for aphids, despite the reduction in thrips and whitefly
      densities. Therefore, our results suggest that the use of mirids combined with A.
      swirskii could result in more efficient and robust biological control programs in
      sweet pepper crops.

PMID- 29596646
TI  - New single capsule of bismuth, metronidazole and tetracycline given with
      omeprazole versus quadruple therapy consisting of bismuth, omeprazole,
      amoxicillin and clarithromycin for eradication of Helicobacter pylori in duodenal
      ulcer patients: a Chinese prospective, randomized, multicentre trial.
AB  - Objectives: To assess the efficacy and safety of omeprazole given with the new
      single capsule of bismuth, metronidazole and tetracycline (OBMT) compared with
      quadruple treatment consisting of omeprazole, bismuth, amoxicillin and
      clarithromycin (OBAC) for Helicobacter pylori eradication in duodenal ulcer
      patients. Methods: This single-blind, randomized multicentre trial was conducted
      in 10 tertiary hospitals in China between January 2013 and April 2014. Patients
      were randomized to receive 10 days of OBMT therapy or 10 days of OBAC therapy.
      Our primary outcome was the H. pylori eradication rate, confirmed by negative
      [13C]urea breath tests 20-25 days after the end of omeprazole maintenance.
      Antibiotic resistance was determined by Etest. This study is registered with
      ClinicalTrials.gov, number ChiCTR-TRC-13003143. Results: One hundred and ninety
      two patients received OBMT therapy and 192 received OBAC therapy. There was no
      significant difference between the eradication rates achieved by OBMT and OBAC in
      either the ITT analysis (86.46% versus 87.50%, P = 0.762) or the PP analysis
      (94.58% versus 93.06%, P = 0.563). The efficacies of OBMT and OBAC were not
      affected by metronidazole or clarithromycin resistance. Treatment-emergent
      adverse events (TEAEs) for both treatments were similar; gastrointestinal and CNS
      symptoms were the most commonly reported. Conclusions: The new single-capsule
      OBMT quadruple therapy is as effective and well tolerated as the widely used OBAC
      therapy for treatment of H. pylori in clinical practice in China. In addition,
      this OBMT therapy largely overcomes H. pylori metronidazole and clarithromycin
      resistance.

PMID- 29596647
TI  - ASAS-SSR Triennial Reproduction Symposium: Looking Back And Moving Forward-How
      Reproductive Physiology Has Evolved: Male reproductive behavior: sensory
      signaling in the brain of low-performing domestic rams.
AB  - Rams are selected for genetic traits a producer desires to propagate in his
      flock. Even though practically all sheep are naturally bred, rams are rarely
      evaluated for expression of sexual interest or behavior. Research at the U.S.
      Sheep Experiment Station reported that the proportion of rams with limited
      interest in ewes was nearly 30% of the total number of breeding rams. Breeding
      soundness tested rams with low sexual interest sire less than 16% of the lamb
      crop. Although producers recognize the problem, their usual solution is to
      increase the number of rams in breeding flocks decreasing the risk of open ewes.
      Increased costs and a lack of genetic progress are clearly important
      considerations, but the biological question as to what controls sexual interest
      remains intriguing. Circulating concentrations of testosterone do not differ by
      sexual interest among rams. However, following exposure to estrous ewes, sexually
      active, but not inactive, rams exhibit an increase in LH pulsatile activity, a
      biological response to sexual stimuli. This begs the question as to whether
      sexually inactive rams recognize sexual cues. Using c fos activity as an
      indicator of neural activity, differences in the olfactory pathway were compared
      among sexually active and inactive rams. Differences in fos activity were not
      detected in the olfactory bulb or medial amygdala. However, sexually inactive
      rams had lower fos activity in the central amygdala, bed nucleus of the stria
      terminalis, and medial preoptic area of the hypothalamus following exposure to
      sexual evocative olfactory stimuli. This suggests sexually inactive rams detect
      olfactory cues but have decreased vigilance to sensory stimuli and a muted
      response to sexual signals in areas of the brain required for the execution of
      sexual performance. With the amygdala receiving and integrating sensory signals
      from many areas of the brain, sexually inactive rams may lack normal reward
      mechanisms contributing to their lack of sexual interest. Rams with limited
      sexual interest have decreased dopamine synthesis and a lower expression of
      dopamine D2 receptors following exposure to sexual stimuli. Thus, a tempered
      reward pathway in combination with decreased vigilance and sensory processing in
      the amygdala may reduce stimulation and/or responsiveness in areas of the brain
      required for expression of sexual behavior.

PMID- 29596648
TI  - Quantification of an Exercise Rehabilitation Program for Severely Burned
      Children: The Standard of Care at Shriners Hospitals for Children(r)-Galveston.
AB  - Currently, there are no clear guidelines for the implementation of rehabilitative
      exercise training (RET) in burned individuals. Therefore, we quantified the
      training logs for exercise intensity, frequency, and duration of 6 weeks of this
      program to develop a basic framework for outpatient RET in patients recovering
      from severe burns. Thirty-three children (11 female, [mean +/- SD] 12 +/- 3
      years, 145 +/- 18 cm, 40 +/- 11 kg, 49 +/- 31 BMI percentile) with severe burns
      (49 +/- 15% total body surface area burned, with 35 +/- 22% third-degree burns)
      completed our 6-week resistance and aerobic exercise training program.
      Cardiorespiratory fitness (peak VO2), strength, power, and lean body mass (LBM)
      were measured before and after RET. Outcome measures were analyzed as a relative
      percentage of values in age- and sex-matched nonburned children (11 female, 12 +/
      3 years, 154 +/- 20 cm, 49 +/- 22 kg, 56 +/- 25 BMI percentile). At discharge,
      burned children had lower LBM (77% of age-sex-matched nonburn values), peak
      torque (53%), power (62%), and cardiorespiratory fitness (56%). After 6 weeks of
      training, LBM increased by 5% (82% of nonburn values), peak torque by 18% (71%),
      power by 20% (81%), and cardiorespiratory fitness by 18% (74%; P < .0001 for
      all). Quantification of data in exercise training logs suggested that physical
      capacity can be improved by aerobic exercise training performed at five metabolic
      equivalents (>70% of peak VO2) at least 3 days/week and 150 minutes/week and by
      resistance training performed at volume loads (reps * sets * weight) of 131 kg
      for the upper body and 275 kg for the lower body for 2 days/week. We present for
      the first time the quantification of our RET and provide clear exercise
      prescription guidelines specific to children with severe burn injury.

PMID- 29596650
TI  - Micronutrients, iodine status and concentrations of thyroid hormones: a
      systematic review.
AB  - Context: The metabolism of thyroid hormones, which are essential for normal
      development, involves many proteins and enzymes. It requires iodine as a key
      component but is also influenced by several other micronutrients, including
      selenium, zinc, iron, and vitamin A. Objective: This systematic review was
      designed to investigate the effect of micronutrient status and supplementation on
      iodine status and thyroid hormone concentrations. Data Sources: Using the PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines,
      electronic databases were searched from their inception to April 2016. Study
      Selection: Human studies published in English and reporting data on micronutrient
      status and iodine status and/or thyroid hormone concentrations were included.
      Studies that examined the effect of micronutrient supplementation on iodine
      status and/or thyroid hormone concentrations were also included. Data Extraction:
      A predesigned and piloted data extraction form was used to compile data from
      individual studies. Results: A total of 57 studies were included: 20 intervention
      studies and 37 observational studies. Although observational evidence suggests
      that concentrations of selenium, zinc, and iron are positively associated with
      iodine status, data from randomized controlled trials fail to confirm this
      relationship. Conclusions: Further studies are needed to provide greater
      understanding of the role of micronutrient status in iodine nutrition and thyroid
      function to ascertain the public health implications for populations worldwide.

PMID- 29596652
TI  - Corrigendum.

PMID- 29596649
TI  - The loss of SMG1 causes defects in quality control pathways in Physcomitrella
      patens.
AB  - Nonsense-mediated mRNA decay (NMD) is important for RNA quality control and gene
      regulation in eukaryotes. NMD targets aberrant transcripts for decay and also
      directly influences the abundance of non-aberrant transcripts. In animals, the
      SMG1 kinase plays an essential role in NMD by phosphorylating the core NMD factor
      UPF1. Despite SMG1 being ubiquitous throughout the plant kingdom, little is known
      about its function, probably because SMG1 is atypically absent from the genome of
      the model plant, Arabidopsis thaliana. By combining our previously established
      SMG1 knockout in moss with transcriptome-wide analysis, we reveal the range of
      processes involving SMG1 in plants. Machine learning assisted analysis suggests
      that 32% of multi-isoform genes produce NMD-targeted transcripts and that splice
      junctions downstream of a stop codon act as the major determinant of NMD
      targeting. Furthermore, we suggest that SMG1 is involved in other quality control
      pathways, affecting DNA repair and the unfolded protein response, in addition to
      its role in mRNA quality control. Consistent with this, smg1 plants have
      increased susceptibility to DNA damage, but increased tolerance to unfolded
      protein inducing agents. The potential involvement of SMG1 in RNA, DNA and
      protein quality control has major implications for the study of these processes
      in plants.

PMID- 29596653
TI  - Corrigendum: Effects of Wind Turbine Noise on Self-Reported and Objective
      Measures of Sleep.

PMID- 29596651
TI  - The Influence of Obesity on the Pharmacokinetics of Dioxin in Mice: An Assessment
      Using Classical and PBPK Modeling.
AB  - The effects of body fat mass on the elimination of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) was examined in mice. When male C57BL/6J mice are fed a high-fat,
      simple carbohydrate diet (HFD) for 13 weeks, they develop an obese phenotype. In
      contrast, A/J mice fed an HFD do not become obese. After 13 weeks on a normal
      diet (ND) or HFD, male C57BL/6J and A/J mice received a single dose by gavage of
      0.1 or 5.0 ug of 2,3,7,8-tetrachloro[1,6-3H] dibenzo-p-dioxin per kg body weight.
      Using classical pharmacokinetics, the blood elimination half-life of TCDD was
      approximately 10 and 2 times longer in the C57BL/6J on the HFD compared with the
      mice on the ND at 0.1 and 5.0 MUg/kg doses, respectively. The diet did not
      increase the blood half-life of TCDD in the A/J mice, which did not get obese.
      Using a physiologically based pharmacokinetic model for TCDD that incorporated
      experimentally derived percent body fat mass and tissue partition coefficients,
      as well as data on hepatic sequestration, did not provide accurate predictions to
      the data and could not explain the increase in half-life of TCDD in the HFD
      groups. This work demonstrates that obesity influences the half-life of TCDD, but
      other undetermined factors are involved in its elimination because the increase
      in body fat mass, decreases in cytochrome P4501A2, and altered partition
      coefficients could not completely explain the prolonged half-life.

PMID- 29596654
TI  - Effects of Irradiation Dose on Sperm Production, Insemination, and Male Mating
      Possible Period in the Sweetpotato Weevil (Coleoptera: Brentidae).
AB  - The sterile insect technique (SIT) has been used for the control or eradication
      of target insect pests. To successfully apply SIT, it is very important to
      clarify the effect of irradiation on male reproduction in the target pest,
      because their mating and spermiogenesis abilities affect the success of
      eradication program. The sweetpotato weevil, Cylas formicarius (Fabricius)
      (Coleoptera: Brentidae) is a notorious and worldwide pest of sweet potato. We
      investigated the effect of irradiation at five doses ranging from 0 (control) to
      150 Gy on 9-d-old males. Survival rate of the control (no treatment) remained
      high from day 10 to 20 of adult life, whereas higher doses of irradiation reduced
      it, maximally by approximately 70%. Mating rates showed a similar tendency.
      Radiation dose neither affected sperm production nor sperm transfer at any dose,
      although spermiogenesis is active during the adult stage. However, radiation dose
      affected the lifetime total of ejaculated sperm number, likely because of fewer
      matings by irradiated males. These results suggest that use of a dose of 150 Gy
      or higher is appropriate for the final step of eradication of this weevil. At
      least, lower dose of irradiation may arise the inadequate sterilization,
      resulting in a failure of eradication program. We conclude that weekly release of
      sweetpotato weevil sterilized with high dose, achieving complete sterilization,
      could be useful for eradication program after reducing the population by male
      annihilation method.

PMID- 29596656
TI  - On the Issue of the Derivation of Permitted Daily Exposure for the Androgen
      Receptor Antagonist Flutamide.

PMID- 29596655
TI  - Enhanced Hepatic PPARalpha Activity Links GLUT8 Deficiency to Augmented
      Peripheral Fasting Responses in Male Mice.
AB  - The adaptive fasting response is invoked as a promising cardiometabolic and
      neurodegenerative therapeutic pathway. We and others have defined the
      carbohydrate transporter glucose transporter 8 (GLUT8) as a critical regulator of
      hepatic and whole-organism metabolic homeostasis in the overfed and diabetic
      states. However, the functions of this critical transporter in the physiological
      fasting response remain poorly understood. Here, we tested the hypothesis that
      GLUT8 modulates the adaptive hepatic fasting response. We demonstrate that mice
      with targeted Slc2a8 disruption exhibit enhanced thermogenesis, ketogenesis, and
      peripheral lipid mobilization during fasting. These metabolic enhancements were
      observed in the context of mildly impaired hepatic mitochondrial oxidative
      metabolism in vivo and in vitro. Mechanistically, we show that hepatic peroxisome
      proliferator-activated receptor alpha (PPARalpha) and its transcriptional fasting
      response target hepatokine, fibroblast growth factor (FGF)21, are cell
      autonomously hyperactivated in GLUT8-deficient liver and in isolated primary
      murine hepatocytes during nutrient depletion. Hepatic PPARalpha knockdown in
      GLUT8-deficient mice normalized the enhanced ketogenic and FGF21 secretory
      responses and decreased mitochondrial respiratory function without altering the
      hyperthermic response to fasting. Our data demonstrate that hepatocyte GLUT8
      regulates adaptive fasting in part through regulation of the PPARalpha signaling
      cascade. Moreover, the ketotic and thermic responses to fasting are
      differentially encoded within the GLUT8-PPARalpha communication axis. GLUT8
      therefore represents a therapeutic target that can be leveraged against
      cardiometabolic disease.

PMID- 29596658
TI  - Effect of resveratrol supplementation on cognitive performance and mood in
      adults: a systematic literature review and meta-analysis of randomized controlled
      trials.
AB  - Context: The aim of this systematic review was to evaluate clinical trial data
      regarding the effect of resveratrol supplementation on cognitive performance and
      mood in populations that are healthy and in the clinical setting. Data Sources:
      Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines, a systematic literature review of randomized controlled
      trials was conducted. Data Extraction: A meta-analysis was also conducted to
      determine treatment effect on the following cognitive domains and mental
      processes: processing speed, number facility, memory, and mood. Risk of bias was
      assessed using the Cochrane Collaboration Risk of Bias tool. Quality of the body
      of evidence was assessed by evidence for each outcome related to cognitive
      function for which data was assessed using the Grading of Recommendations,
      Assessment, Development, and Evaluation (GRADE). Results: Ten studies were
      included. Three studies found resveratrol supplementation significantly improved
      some measures of cognitive performance, 2 reported mixed findings, and 5 found no
      effect. When data were pooled, resveratrol supplementation had a significant
      effect on delayed recognition (standardized mean difference [SMD], 0.39; 95%
      confidence interval [CI], 0.08-0.70; I2 = 0%; P = 0.01; n = 3 studies; n = 166
      participants) and negative mood (SMD, -0.18; 95%CI, -0.31 to -0.05; I2 = 0%; P =
      0.006; n = 3 studies; n = 163 participants). Included studies generally had low
      risk of bias and were of moderate or high quality. Conclusions: The results of
      this review indicate that resveratrol supplementation might improve select
      measures of cognitive performance; however, the current literature is
      inconsistent and limited.

PMID- 29596657
TI  - Attenuating effect of melatonin on lipopolysaccharide-induced chicken small
      intestine inflammation.
AB  - Enriched melatonin (MEL) has been found in the mammalian intestine and has been
      recently demonstrated to alleviate rodent colitis. In this study, the effect of
      MEL on lipopolysaccharide (LPS)-induced intestinal inflammations was investigated
      in new chicken hatchlings. The chicks were fed with a diet supplemented with MEL
      (12.5 mg/day) from D1 to D10. Meanwhile, the chicks in the LPS or MEL + LPS
      groups were injected with LPS (10 mg/kg BW, i.p.) at D10. LPS treatment for 6 h
      increased the expression of IL-6, IL-4, caspase-3 mRNAs and TUNEL-positive cell
      populations, but decreased populations of the goblet and PCNA+ cells, IgA
      production and the expression of MUC2 mRNA in the duodenum. Compared with the LPS
      group, MEL pre-feeding alleviated duodenal inflammation and decreased the
      expression of TNF-alpha mRNAs by 23.6% (P = 0.004), IL-6 mRNAs by 69.4% (P =
      0.001), IL-4 mRNAs by 4.1% (P = 0.824) and caspase-3 mRNAs by 45.8% (P < 0.001).
      Conversely, MEL pre-feeding attenuated the LPS-induced changes of IgA production
      by 161.6% (P = 0.013) and PCNA+ cell populations by 172.1% (P < 0.001) in the
      duodenum. TLR4 mRNA was also up-regulated by LPS treatment but down-regulated by
      MEL pre-feeding. In conclusion, dietary MEL could attenuate LPS-induced chick
      duodenal inflammation by down-regulating the expression of inflammatory
      cytokines, promoting epithelial cell proliferation, improving the immunological
      barrier and inhibiting epithelial apoptosis via the mediation of TLR4.

PMID- 29596659
TI  - The degree of radiation-induced DNA strand breaks is altered by acute sleep
      deprivation and psychological stress and is associated with cognitive performance
      in humans.
AB  - Study Objectives: Sleep deprivation is associated with impaired immune responses,
      cancer, and morbidity and mortality, and can degrade cognitive performance,
      although individual differences exist in such responses. Sleep deprivation
      induces DNA strand breaks and DNA base oxidation in animals, and psychological
      stress is associated with increased DNA damage in humans. It remains unknown
      whether sleep deprivation or psychological stress in humans affects DNA damage
      response from environmental stressors, and whether these responses predict
      cognitive performance during sleep deprivation. Methods: Sixteen healthy adults
      (ages 29-52 years; mean age +/- SD, 36.4 +/- 7.1 years; seven women) participated
      in a 5-day experiment involving two 8 hr time-in-bed (TIB) baseline nights,
      followed by 39 hr total sleep deprivation (TSD), and two 8-10 hr TIB recovery
      nights. A modified Trier Social Stress Test was conducted on the day after TSD.
      The Psychomotor Vigilance Test measured behavioral attention. DNA damage was
      assessed in blood cells collected at 5 time points, and blood cells were
      irradiated ex vivo. Results: TSD, alone or in combination with psychological
      stress, did not induce significant increases in DNA damage. By contrast,
      radiation-induced DNA damage decreased significantly in response to TSD, but
      increased back to baseline when combined with psychological stress. Cognitively
      vulnerable individuals had more radiation-induced DNA strand breaks before TSD,
      indicating their greater sensitivity to DNA damage from environmental stressors.
      Conclusions: Our results provide novel insights into the molecular consequences
      of sleep deprivation, psychological stress, and performance vulnerability. They
      are important for fields involving sleep loss, radiation exposure, and cognitive
      deficits, including cancer therapy, environmental toxicology, and space medicine.

PMID- 29596660
TI  - Metabolic Activation of the Cooked Meat Carcinogen 2-Amino-1-Methyl-6
      Phenylimidazo[4,5-b]Pyridine in Human Prostate.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), an heterocyclic aromatic
      amine (HAA) formed in cooked meat, is a rodent and possible human prostate
      carcinogen. Recently, we identified DNA adducts of PhIP in the genome of prostate
      cancer patients, but adducts of 2-amino-3, 8-dimethylmidazo[4,5-f]quinoxaline
      (MeIQx) and 2-amino-9 H-pyrido[2,3-b]indole (AalphaC), other prominent HAAs
      formed in cooked meats, were not detected. We have investigated the bioactivation
      of HAAs by Phase I and II enzymes in the human prostate (LNCaP) cell line using
      cytotoxicity and DNA adducts as endpoints. PhIP, MeIQx, and 2-amino-3
      methylimidazo[4,5-f]quinoline, another HAA found in cooked meats, were poorly
      bioactivated and not toxic. The synthetic genotoxic N-hydroxylated-HAAs were also
      assayed in LNCaP cells with Phase II enzyme inhibitors. Notably, 2-hydroxy-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), but not other HONH-HAAs,
      induced cytotoxicity. Moreover, PhIP-DNA adduct formation was 20-fold greater
      than adducts formed with other HONH-HAAs. Pretreatment of LNCaP cells with
      mefenamic acid, a specific inhibitor of sulfotransferase (SULT1A1), decreased
      PhIP-DNA adducts by 25%, whereas (Z)-5-(2'-hydroxybenzylidene)-2
      thioxothiazolidin-4-one and pentachlorophenol, inhibitors of SULTs and N
      acetyltransferases (NATs), decreased the PhIP-DNA adduct levels by 75%. NATs in
      cytosolic fractions of LNCaP cells and human prostate catalyzed DNA binding of
      HONH-PhIP by up to 100-fold greater levels than for SULT and kinase activities.
      Recombinant NAT2 is catalytically superior to recombinant NAT1 in the
      bioactivation of HONH-PhIP; however, the extremely low levels of NAT2 activity in
      prostate suggest that NAT1 may be the major isoform involved in PhIP-DNA damage.
      Thus, the high susceptibility of LNCaP cells recapitulates the DNA-damaging
      effect of HONH-PhIP in rodent and human prostate.

PMID- 29596662
TI  - Impact of Question Type and Question Order on Tobacco Prevalence Estimates in
      U.S. Young Adults: A Randomized Experiment.
AB  - Implications: This study identifies the effects of question type, order, and
      inclusion of product images on tobacco use estimates in a national sample of
      young adults. Ever use and past 30-day use prevalence estimates of specific
      products were impacted by respondents answering breakout items or breakout items
      with images compared to respondents answering a checklist of items in the survey.
      Current surveys that include a "select all that apply" list format may be
      underestimating ever and past 30-day prevalence estimates of tobacco products.

PMID- 29596663
TI  - Assessing Psychological Fitness in the Military - Development of an Effective and
      Economic Screening Instrument.
AB  - Background: There are a high number of soldiers with deployment-related and non
      deployment-related mental health problems in the German Armed Forces
      (Bundeswehr): This has led to an increase in mental disorders and a decrease in
      quality of life. To tackle these problems and to strengthen resources among the
      Bundeswehr personnel, this study aims at developing a screening instrument for
      assessing the psychological fitness of soldiers on the basis of questionnaire
      scales. In this approach, psychological fitness describes a soldier's ability to
      integrate and enhance his/her mental and emotional capabilities using resources
      and trainable skills. Methods: Bundeswehr combat soldiers (N = 361) answered
      questionnaires about resilience (RS-11), sense of coherence (SOC-L9), quality of
      life (WHOQOL-BREF), mental disorders (PHQ-D) and post-traumatic growth (PTG).
      Additionally, they were interviewed by trained troop psychologists both before
      and after their deployment in Afghanistan from January to June 2014. The
      screening model is based on self-report data; the psychological fitness in the
      standardized interview serves as a validation standard. Findings: A linear
      logistic regression model was performed that includes the social relationship and
      the psychological scale from WHOQOL-BREF and the somatoform and the stress scale
      from PHQ. This model allows specialists a first assessment between participants
      who are psychologically fit before and after deployment and those who are less
      so. The chosen cutoff for sensitivity is between 70% and 79% and for specificity
      between 70% and 85%. Discussion: This screening approach is still not applicable
      to large populations like that of the Bundeswehr, which currently has about
      170,000 soldiers but it is limited to deployed combat troops. Classifying
      psychological fitness allows specialists to differentiate between people in need
      of special training or additional diagnostic measures and those in need of
      sustaining their fitness regularly at the earliest possible stage. A follow-up
      study that is representative of deployed and non-deployed military personnel will
      examine whether these results can be transferred to the entire Bundeswehr and
      whether the validity of the interview can be established.

PMID- 29596664
TI  - From the Archives.

PMID- 29596665
TI  - Measures of metabolism provide insights into hippocampal sclerosis.

PMID- 29596666
TI  - Discovery of a cause of vein of Galen malformations.

PMID- 29596667
TI  - 'Chase': in dogged pursuit of a therapy for spinal cord injury.

PMID- 29596668
TI  - Synaptic or ion channel modifier? PRRT2 is a chameleon-like regulator of neuronal
      excitability.

PMID- 29596669
TI  - Editorial.

PMID- 29596661
TI  - Mitochondrial Agents for Bipolar Disorder.
AB  - Background: Bipolar disorder is a chronic and often debilitating illness. Current
      treatment options (both pharmaco- and psychotherapy) have shown efficacy, but for
      many leave a shortfall in recovery. Advances in the understanding of the
      pathophysiology of bipolar disorder suggest that interventions that target
      mitochondrial dysfunction may provide a therapeutic benefit. Methods: This review
      explores the current and growing theoretical rationale as well as existing
      preclinical and clinical data for those therapies aiming to target the
      mitochondrion in bipolar disorder. A Clinicaltrials.gov and ANZCTR search was
      conducted for complete and ongoing trials on mitochondrial agents used in
      psychiatric disorders. A PubMed search was also conducted for literature
      published between January 1981 and July 2017. Systematic reviews, randomized
      controlled trials, observational studies, case series, and animal studies with an
      emphasis on agents affecting mitochondrial function and its role in bipolar
      disorder were included. The search was augmented by manually searching the
      references of key papers and related literature. The results were presented as a
      narrative review. Results: Mitochondrial agents offer new horizons in mood
      disorder treatment. While some negative effects have been reported, most
      compounds are overall well tolerated and have generally benign side-effect
      profiles. Conclusions: The study of neuroinflammation, neurodegeneration, and
      mitochondrial function has contributed the understanding of bipolar disorder's
      pathophysiology. Agents targeting these pathways could be a potential therapeutic
      strategy. Future directions include identification of novel candidate
      mitochondrial modulators as well as rigorous and well-powered clinical trials.

PMID- 29596670
TI  - Facilitating fluency in adults who stutter.

PMID- 29596671
TI  - The multiforme of glioblastoma.

PMID- 29596673
TI  - Organizational justice and the psychological contract.

PMID- 29596674
TI  - Implementation of the Directive 89/391/EEC in Europe.

PMID- 29596675
TI  - New and emerging risks of chemical carcinogens: detection and prevention.

PMID- 29596676
TI  - Reply.

PMID- 29596677
TI  - Is there a need for specific smoking cessation programs for the military?

PMID- 29596678
TI  - Follow the Blue Feet: Nurse Implemented Postoperative MOBILITY Program.
AB  - To establish the effectiveness of a nurse-led postoperative MOBILITY program
      implemented on the Burn/Surgical/Trauma unit at our facility to increase
      documentation of patient mobility and to develop nurse and patient understanding
      of the importance of movement in postoperative recovery while increasing patient
      satisfaction with mobility. The MOBILITY program was implemented on a 24-bed
      Burn/Surgical/Trauma unit. Lewin's Change Theory guided the development of the
      program, while the Iowa Model of Evidence-Based Practice for Quality Care was the
      framework for the project. Nursing staff (n = 20) on the Burn/Trauma unit
      completed pre/postimplementation MOBILITY surveys. Pre/postimplementation
      MOBILITY patient (n = 9) satisfaction questionnaires were completed by
      postoperative patients. Retrospective chart (n = 10) audits were performed
      pre/postimplementation. Included in the chart audits and patient satisfaction
      surveys were patients 72 hours or less postoperatively without lower limb weight
      bearing restrictions. Those excluded were patients on complete bed rest, or those
      with bilateral or unilateral nonweight-bearing orders. Documentation of mobility
      improved by 233.3%, while ambulation distance documentation increased by 700%.
      Mobility orders entered by the medical team rose by 66.7% postintervention.
      Nurses' comfort level with assessing mobility improved by 38.5%. Knowledge of
      where to document patient postoperative mobility improved by 80%.
      Postintervention patient satisfaction with postoperative mobility saw a 60%
      change. Patients performing postoperative mobility increased by 80%.
      Implementation of a nurse-led postoperative MOBILITY program on a
      Burn/Surgical/Trauma unit showed a marked increase in nurse and patient
      understanding of postoperative mobility, patient satisfaction with postoperative
      mobility, and nursing documentation of patient mobility.

PMID- 29596679
TI  - Burn Injuries in Patients with Paralysis: A National Perspective on Injury
      Patterns and Outcomes.
AB  - The affect of paralysis-related comorbidities on outcomes in burn-injured
      patients has not been explored. We hypothesize that comorbid paralysis is
      associated with increased morbidity in this population. All burned patients with
      prior diagnoses of paralysis were identified from the National Burn Repository
      (Version 8.0). One-to-one matching of nonparalyzed burn-injured patients was
      performed, and nonparametric analysis was used to compare the groups. We
      identified 432 paralyzed patients, who were predominantly male (70.6%) and
      Caucasian (57.6%), with an average age of 40.8 +/- 19.0 years. The identified
      level of disability was distinguished as paraplegia (59.5%), hemiplegia (16.9%),
      quadriplegia (13.9%), or other (9.8%). A majority of injuries occurred in the
      home (75.2%), primarily due to scalds (48.1%). More than half sustained small
      injuries with affected total body surface area <5%. Lower extremities were
      frequently injured (72.2%), with 41.0% affecting exclusively the lower
      extremities. While the paralysis population had significantly longer hospital
      lengths of stay, nonparalyzed patients had longer intensive care unit length of
      stay and ventilator days (P < .001). There was no statistically significant
      difference in mortality rate between paralyzed and nonparalyzed patients (4.4% vs
      4.9%, P = .550). Patients with paralysis are susceptible to small scald injuries
      in the home. Comorbid paralysis places patients at risk for longer, more indolent
      hospital stays, when compared with matched nonparalyzed patients with more
      critical illness. Further investigation is needed regarding the pathophysiologic
      mechanisms predisposing paralyzed burn patients to increased morbidity.

PMID- 29596680
TI  - Differential antiviral activities of respiratory syncytial virus (RSV) inhibitors
      in human airway epithelium.
AB  - Objectives: We report the use of reconstituted 3D human airway epithelium cells
      (HuAECs) of bronchial origin in an air-liquid interface to study respiratory
      syncytial virus (RSV) infection and to assess the efficacy of RSV inhibitors in
      (pre-)clinical development. Methods: HuAECs were infected with RSV-A Long strain
      (0.01 CCID50/cell, where CCID50 represents 50% cell culture infectious dose in
      HEp2 cells) on the apical compartment of the culture. At the time of infection or
      at 1 or 3 days post-infection, selected inhibitors were added and refreshed daily
      on the basal compartment of the culture. Viral shedding was followed up by apical
      washes collected daily and quantifying viral RNA by RT-qPCR. Results: RSV-A
      replicates efficiently in HuAECs and viral RNA is shed for weeks after infection.
      RSV infection reduces the ciliary beat frequency of the ciliated cells as of 4
      days post-infection, with complete ciliary dyskinesia observed by day 10.
      Treatment with RSV fusion inhibitors resulted in an antiviral effect only when
      added at the time of infection. In contrast, the use of replication inhibitors
      (both nucleoside and non-nucleoside) elicited a marked antiviral effect even when
      the start of treatment was delayed until 1 day or even 3 days after infection.
      Levels of the inflammation marker RANTES (mRNA) increased ~200-fold in infected,
      untreated cultures (at 3 weeks post-infection), but levels were comparable to
      those of uninfected cultures in the presence of PC786, an RSV replication
      inhibitor, suggesting that an efficient antiviral treatment might inhibit virus
      induced inflammation in this model. Conclusions: Overall, HuAECs offer a robust
      and physiologically relevant model to study RSV replication and to assess the
      efficacy of antiviral compounds.

PMID- 29596681
TI  - Glycoengineering design options for IgG1 in CHO cells using precise gene editing.
AB  - Precise gene editing technologies are providing new opportunities to stably
      engineer host cells for recombinant production of therapeutic glycoproteins with
      different glycan structures. The glycosylation of recombinant therapeutics has
      long been a focus for both quality and consistency of products and for optimizing
      and improving pharmacokinetic properties as well as bioactivity. Structures of
      glycans on therapeutic glycoproteins are important for circulation,
      biodistribution and bioactivity. In particular, the latter has been demonstrated
      for therapeutic IgG1 antibodies where the core alpha1,6Fucose on the conserved N
      glycan at Asn297 have remarkable dampening effects on antibody effector
      functions. We previously explored precise gene engineering and design options for
      N-glycosylation in CHO cells, and here we focus on engineering options possible
      for N-glycans on human IgG1. We demonstrate stable precise gene engineering of
      rather homogenous biantennary N-glycans with and without galactose (G0F, G2F) as
      well as the alpha2,6-linked monosialylated (G2FS1) glycoform. We were unable to
      introduce substantial disialylated glycoforms. Instead we engineered a novel
      monoantennary homogeneous N-glycan design with complete alpha2,6-linked sialic
      acid capping. All N-glycoforms may be engineered with and without core
      alpha1,6Fucose. The stably engineered design options enable production of human
      IgG antibodies with an array of distinct glycoforms for testing and selection of
      optimal design for different therapeutic applications.

PMID- 29596682
TI  - Helping the healer: population-informed workplace wellness recommendations for
      physician well-being.
AB  - Background: The need to keep physicians healthy and in practice is critical as
      demand for doctors grows faster than the supply. Workplace wellness programmes
      can improve employee health and retain skilled workers. Aims: To broaden our
      understanding about ways to help doctors coping with mental health problems and
      to develop population-informed workplace wellness recommendations for physician
      populations. Methods: Researchers surveyed physicians to document potential
      warning signs and prevention strategies. A survey was issued to doctors who
      presented to a physician health programme with mental health complaints. The
      survey captured respondents' feedback about how to identify and prevent mental
      health problems. Data were analyzed using simple descriptive statistics. Results:
      There were 185 participants. Half of respondents believed their problems could
      have been recognized sooner and 60% said they exhibited signs that could aid in
      earlier detection. Potential warnings included fluctuations in mood (67%),
      increased comments about stress/burnout (49%) and behavioural changes (32%). To
      improve detection, prevention and care-seeking for mental health problems,
      doctors endorsed multiple items related to the use of interpersonal supports,
      personal factors and organizational dynamics throughout the survey. Conclusions:
      The findings confirmed earlier work demonstrating the value of social and
      organizational support in maintaining physician health. It further indicated that
      earlier identification and/or prevention of mental health problems is not only
      possible, but that medical organizations are uniquely situated to carry out this
      work.

PMID- 29596683
TI  - Marjolin's Ulcer Arising in a Burn Scar.
AB  - Marjolin's ulcer is an aggressive disease arising in chronic wounds and cutaneous
      scars. Corbo et al define Marjolin's ulcer an often overlooked or misdiagnosed
      tumor. We report a case of Marjolin's ulcer arose in a burn scar of a 51-year-old
      man who sustained a burn in childhood. A punch biopsy showed squamous cell
      carcinoma. The lesion was surgically removed with wide excision. The loss of
      substance was covered with a partial-thickness skin graft, harvested from the
      left thigh with dermatome. Histological examination confirmed a well
      differentiated squamous cell carcinoma. Burn scars are the most commonly
      associated with these tumors, but other lesions may initiate this malignant
      transformation. The most common type of tumor reported in a Marjolin's ulcer is
      squamous cell carcinoma, but Pavlovic et al reported other malignancies.

PMID- 29596684
TI  - Phenomenological Load on Model Parameters Can Lead to False Biological
      Conclusions.
AB  - When a substitution model is fitted to an alignment using maximum likelihood, its
      parameters are adjusted to account for as much site-pattern variation as
      possible. A parameter might therefore absorb a substantial quantity of the total
      variance in an alignment (or more formally, bring about a substantial reduction
      in the deviance of the fitted model) even if the process it represents played no
      role in the generation of the data. When this occurs, we say that the parameter
      estimate carries phenomenological load (PL). Large PL in a parameter estimate is
      a concern because it not only invalidates its mechanistic interpretation (if it
      has one) but also increases the likelihood that it will be found to be
      statistically significant. The problem of PL was not identified in the past
      because most off-the-shelf substitution models make simplifying assumptions that
      preclude the generation of realistic levels of variation. In this study, we use
      the more realistic mutation-selection framework as the basis of a generating
      model formulated to produce data that mimic an alignment of mammalian
      mitochondrial DNA. We show that a parameter estimate can carry PL when 1) the
      substitution model is underspecified and 2) the parameter represents a process
      that is confounded with other processes represented in the data-generating model.
      We then provide a method that can be used to identify signal for the process that
      a given parameter represents despite the existence of PL.

PMID- 29596685
TI  - Activity matters: a web-based resource to enable people with multiple sclerosis
      to become more active.
AB  - Increasing physical activity (PA) through exercise is associated with
      improvements in many of the symptoms associated with multiple sclerosis (MS) such
      as fatigue, strength, balance, and mobility. Despite this, people with MS remain
      largely inactive. Interventions that are grounded in theory and that aim to
      change PA behavior need to be developed. The purpose of this study was to
      describe the development process of a web-based resource, namely, "Activity
      Matters," to enable people with MS to become more active. Development of the
      "Activity Matters" online intervention was guided by the UK's Medical Research
      Council (MRC) framework for the development and evaluation of complex
      interventions and the behavior change wheel (BCW). Seven sources of data were
      used to inform the process and were mapped on to both the MRC and BCW frameworks.
      The intervention is theoretically based, and constructs including knowledge,
      memory, attention and decision processes, skills, social influences,
      environmental context and resources, beliefs about capabilities, beliefs about
      consequences, goals, and emotions were recognized as important. "Activity
      Matters" is the first MS PA intervention to be developed using the theoretical
      approach outlined by the BCW and MRC complex interventions frameworks. The next
      phase of this work is to test the usability, acceptability, and preliminary
      effectiveness of "Activity Matters" among people with MS.

PMID- 29596686
TI  - Hypertrophic Scar Severity at Autograft Sites Is Associated With Increased Pain
      and Itch After Major Thermal Burn Injury.
AB  - Approximately three quarters of major thermal burn injury (MThBI) survivors
      suffer from hypertrophic scarring (HTS) and over half experience chronic pain or
      itch. In survivors of MThBI, HTS and chronic pain or itch are considered one of
      the greatest unmet challenges of postburn injury care and psychosocial
      reintegration. Although scarring, itch, and pain have been clinically associated,
      there are no prospective, multisite studies examining tissue autograft site pain
      or itch and scar outcomes. The authors collected a representative cohort (n = 56)
      of MThBI survivors who received autografting within 14 days of injury and
      evaluated graft-site pain or itch severity (0-10 Numeric Rating Scale) and HTS
      using a validated scar photograph assessment scale 6 months following MThBI.
      Given that stress is known to influence wound healing, the authors also assessed
      the relationship between previous trauma exposure, peritraumatic stress, preburn
      overall health (SF-12), scarring, and chronic pain or itch severity using
      Spearman's correlation. Association between HTS and chronic pain or itch was
      significant in a linear regression model adjusted for age, sex, and ethnicity
      (beta = 0.2, P = .033 for pain, beta = 0.2, P = .019 for itch). Results indicate
      that prior trauma exposure is inversely correlated (r = -.363, P = .030) with
      scar severity, but not pain or itch severity 6 months after MThBI. Study results
      suggest that preburn chronic pain or itch is associated with pathological
      scarring 6 months following MThBI. Results also indicate that stress may improve
      scarring after MThBI. Further work to understand the mechanisms that underlie
      both HTS and chronic pain or itch and their relationship to chronic stress is
      critical to the development of novel therapies to assist burn survivors recover.

PMID- 29596687
TI  - Initial predictors of poor survival in myositis-associated interstitial lung
      disease: a multicentre cohort of 497 patients.
AB  - Objective: To identify initial predictors of poor survival in patients with PM/DM
      associated interstitial lung disease (ILD). Methods: We established a multicentre
      retrospective cohort of incident cases of PM/DM-associated ILD from 44
      institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients
      with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ?16
      years; PM/DM or clinically amyopathic DM according to the published criteria;
      imaging evidence of ILD; and availability of serum samples for assays of
      autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti
      aminoacyl tRNA synthetase. We collected demographic data and clinical
      characteristics recorded at the time of diagnosis, as well as follow-up survival
      data. Predictors of ILD-related mortality were identified by univariate and
      multivariate analyses. Results: JAMI enrolled a cohort of 497 patients with PM
      (15%), classic DM (32%) and clinically amyopathic DM (53%). During the
      observation period (median 20 months), 76 died of respiratory insufficiency
      directly related to ILD. Univariate analysis revealed several initial parameters
      associated with ILD mortality, including demographic, clinical, laboratory,
      imaging and autoantibody variables. We used multivariate analysis with a stepwise
      selection of parameters to generate an appropriate predictive model, and
      identified the following independent risk factors for ILD mortality: age at onset
      ?60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ?1 mg/dl (HR = 2.6,
      95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI:
      1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5,
      95% CI: 2.8, 20.2). Conclusion: We established a large cohort of incident cases
      of PM/DM-associated ILD, and successfully identified independent predictors of
      short-term ILD mortality.

PMID- 29596691
TI  - Prevalence and Causes of Visual Loss Among the Indigenous Peoples of the World: A
      Systematic Review.
AB  - Importance: Studies have documented a higher disease burden in indigenous
      compared with nonindigenous populations, but no global data on the epidemiology
      of visual loss in indigenous peoples are available. A systematic review of
      literature on visual loss in the world's indigenous populations could identify
      major gaps and inform interventions to reduce their burden of visual loss.
      Objective: To conduct a systematic review on the prevalence and causes of visual
      loss among the world's indigenous populations. Evidence Review: A search of
      databases and alternative sources identified literature on the prevalence and
      causes of visual loss (visual impairment and blindness) and eye diseases in
      indigenous populations. Studies from January 1, 1990, through August 1, 2017,
      that included clinical eye examinations of indigenous participants and, where
      possible, compared findings with those of nonindigenous populations were
      included. Methodologic quality of studies was evaluated to reveal gaps in the
      literature. Findings: Limited data were available worldwide. A total of 85
      articles described 64 unique studies from 24 countries that examined 79 598
      unique indigenous participants. Nineteen studies reported comparator data on 42
      085 nonindigenous individuals. The prevalence of visual loss was reported in 13
      countries, with visual impairment ranging from 0.6% in indigenous Australian
      children to 48.5% in native Tibetans 50 years or older. Uncorrected refractive
      error was the main cause of visual impairment (21.0%-65.1%) in 5 of 6 studies
      that measured presenting visual acuity. Cataract was the main cause of visual
      impairment in all 6 studies measuring best-corrected acuity (25.4%-72.2%).
      Cataract was the leading cause of blindness in 13 studies (32.0%-79.2%), followed
      by uncorrected refractive error in 2 studies (33.0% and 35.8%). Conclusions and
      Relevance: Most countries with indigenous peoples do not have data on the burden
      of visual loss in these populations. Although existing studies vary in
      methodologic quality and reliability, they suggest that most visual loss in
      indigenous populations is avoidable. Improvements in quality and frequency of
      research into the eye health of indigenous communities appear to be required, and
      coordinated eye care programs should be implemented to specifically target the
      indigenous peoples of the world.

PMID- 29596688
TI  - Age-Related Susceptibility to Epileptogenesis and Neuronal Loss in Male Fischer
      Rats Exposed to Soman and Treated With Medical Countermeasures.
AB  - Elderly individuals compose a large percentage of the world population; however,
      few studies have addressed the efficacy of current medical countermeasures (MCMs)
      against the effects of chemical warfare nerve agent exposure in aged populations.
      We evaluated the efficacy of the anticonvulsant diazepam in an old adult rat
      model of soman (GD) poisoning and compared the toxic effects to those observed in
      young adult rats when anticonvulsant treatment is delayed. After determining
      their respective median lethal dose (LD50) of GD, we exposed young adult and old
      adult rats to an equitoxic 1.2 LD50 dose of GD followed by treatment with
      atropine sulfate and the oxime HI-6 at 1 min after exposure, and diazepam at 30
      min after seizure onset. Old adult rats that presented with status epilepticus
      were more susceptible to developing spontaneous recurrent seizures (SRSs).
      Neuropathological analysis revealed that in rats of both age groups that
      developed SRS, there was a significant reduction in the density of mature neurons
      in the piriform cortex, thalamus, and amygdala, with more pronounced neuronal
      loss in the thalamus of old adult rats compared with young adult rats.
      Furthermore, old adult rats displayed a reduced density of cells expressing
      glutamic acid decarboxylase 67, a marker of GABAergic interneurons, in the
      basolateral amygdala and piriform cortex, and a reduction of astrocyte activation
      in the piriform cortex. Our observations demonstrate the reduced effectiveness of
      current MCM in an old adult animal model of GD exposure and strongly suggest the
      need for countermeasures that are more tailored to the vulnerabilities of an
      aging population.

PMID- 29596692
TI  - The three peaks in age distribution of females with pneumothorax: a nationwide
      database study in Japan.
AB  - OBJECTIVES: Women are the minority among patients with spontaneous pneumothorax,
      but catamenial pneumothorax (CP) is unique to them. We aimed to clarify the
      clinical characteristics of female patients with spontaneous pneumothorax using a
      nationwide database. METHODS: Medical records from the Japanese Diagnosis
      Procedure Combination database for inpatients with pneumothorax between July 2010
      and March 2016 were retrospectively reviewed. Age, underlying diseases, body mass
      index, smoking status, laterality, number of hospitalizations and treatments were
      studied. RESULTS: We identified 157 087 patients with pneumothorax, including 27
      716 (17.6%) women and 129 371 (82.4%) men. The age distribution of female
      patients with pneumothorax had 3 peaks: 18 years, around 40 years and 80 years;
      male patients had 2 peaks: 18 years and 79 years. We identified 873 patients with
      CP; this number was not sufficient to account for the female-specific peak around
      40 years. The characteristics of female patients of reproductive age were
      significantly different between those with and without CP. The patients with CP
      were older (average age: 37.9 +/- 7.7 years vs 31.3 +/- 11.5 years, P < 0.001),
      were right side dominant (right: 64.9%, left: 6.5%), had more hospitalizations
      (average number of hospitalizations: 1.6 +/- 0.9 vs 1.3 +/- 0.6, P < 0.001) and
      had more frequently undergone surgery (57.1% vs 37.3%, P < 0.001). CONCLUSIONS:
      The age distribution of women with pneumothorax had 3 distinct peaks while that
      of men had 2. CP has different characteristics from other types of pneumothorax,
      thus requiring different treatment strategies for women of reproductive age.

PMID- 29596693
TI  - Statistical primer: performing repeated-measures analysis.
AB  - Longitudinal data arise when repeated measurements are taken on the same
      individuals over time. Inference about between-group differences of within
      subject change is usually of interest. This statistical primer for cardiothoracic
      and vascular surgeons aims to provide a short and practical introduction of
      biostatistical methods on how to analyse repeated-measures data. Several
      methodological approaches for analysing repeated measures will be introduced,
      ranging from simple approaches to advanced regression modelling. Design
      considerations of studies involving repeated measures are discussed, and the
      methods are illustrated with a data set measuring coronary sinus potassium in
      dogs after occlusion. Cardiothoracic and vascular surgeons should be aware of the
      myriad approaches available to them for analysing repeated-measures data,
      including the relative merits and disadvantages of each. It is important to
      present effective graphical displays of the data and to avoid arbitrary cross
      sectional statistical comparisons.

PMID- 29596694
TI  - Finding the forest through the trees in statistics: let the Statistical Primers
      in EJCTS/ICVTS guide you.

PMID- 29596696
TI  - Erratum to 'Deep hypothermic circulatory arrest or tepid regional cerebral
      perfusion: impact on haemodynamics and myocardial integrity in a randomized
      experimental trial' [Interact CardioVasc Thorac Surg 2018;26:667-672].

PMID- 29596697
TI  - Survival of patients with prior anti-angiogenic therapy.

PMID- 29596698
TI  - The Scouts Have It Right-BE PREPARED!

PMID- 29596699
TI  - Designing Educational Content Based on Best Available Current Evidence.
AB  - This article, the fourth part of the educational design series, addresses how
      nursing professional development practitioners can meet educational design
      criterion 4 in the American Nurses Credentialing Center primary accreditation
      process and standards 4 and 5 in the Association for Nursing Professional
      Development Nursing Professional Development: Scope and Standards of Practice. J
      Contin Educ Nurs. 2018;49(4):148-150.

PMID- 29596700
TI  - Creating LGBTQ-Inclusive Care and Work Environments.
AB  - In considering the full depth of inclusion in care and work environments (and
      developing inclusive engagement skills for lesbian, gay, bisexual, transgender,
      queer or questioning [LGBTQ] patients and their families), professional
      development leaders must bring these discussions and shared learnings into the
      open. Understanding the LGBTQ population's unique needs is essential to providing
      personalized health care, and inclusive work environments help to foster more
      inclusive care for this population. J Contin Educ Nurs. 2018;49(4):151-153.

PMID- 29596701
TI  - Using Systems Thinking to Advance Global Health Engagement in Education and
      Practice.
AB  - The integration of global health into nursing practice within complex systems
      requires a strategic approach. The System-Level Awareness Model (SAM) can be used
      to guide the process of enhancing systems thinking for global health. The purpose
      of this article is to explain the SAM and how to use it for integrating systems
      thinking into nursing education in academic, professional development, and
      continuing education settings to promote global health across the nursing
      continuum. Tips are provided on how to teach systems thinking for global health
      in nursing education and practice, consistent with continuing education national
      learning competencies for health care professionals. J Contin Educ Nurs.
      2018;49(4):154-156.

PMID- 29596702
TI  - Evaluating the Influence of a Standardized Bedside Handoff Process in a Medical
      Surgical Unit.
AB  - BACKGROUND: Patient safety is a national and global concern. In the United
      States, medical errors result in more than 50,000 unnecessary patient deaths
      annually and contribute to billions of dollars in health care costs. The purpose
      of this project was to evaluate a standardized bedside handoff process and its
      influence in a medical-surgical unit. METHOD: A quality improvement project was
      performed in a medical-surgical unit and consisted of development,
      implementation, and evaluation of a standardized bedside handoff. The project
      included surveying nurses, a web-based educational program, and observations
      using the SBAR (T) competency checklist tool. Data were analyzed for trends.
      RESULTS: Results identified an improved perception of communication among the
      nurses as it relates to shift report and a reduction in length of handoff time
      after the education intervention. CONCLUSION: Continual nurse education and
      audits by nurse leaders are vital to the sustainment of positive outcomes. J
      Contin Educ Nurs. 2018;49(4):157-163.

PMID- 29596703
TI  - Improving Rural Nurse Practitioner Knowledge About Polycystic Ovary Syndrome
      Through Continuing Education.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS), a common androgen-excess disorder
      in reproductive-aged women, is often a missed diagnosis. Rural nurse
      practitioners (NPs) need to be able to diagnose and provide basic management for
      PCOS. This study's objective was to determine whether a continuing education
      program about PCOS would improve NPs' knowledge about PCOS. METHOD: A pretest
      posttest design was used. Forty-eight participants attending a regional NP
      conference completed a pretest before a continuing education presentation about
      PCOS. Afterward, 43 participants completed an identical posttest. A two-step
      multivariate analysis of variance compared the results. RESULTS: Pretest results
      indicated NPs had low levels of knowledge for assessing, diagnosing, and managing
      PCOS. The posttest results demonstrated significant (p = .000) improvements in
      these areas. CONCLUSION: Continuing education presentations have the potential to
      increase rural NPs' knowledge about PCOS so they can provide evidence-based care
      to rural women with PCOS. J Contin Educ Nurs. 2018;49(4):164-170.

PMID- 29596704
TI  - Characteristics of E-Mail Solicitations From Predatory Nursing Journals and
      Publishers.
AB  - Predatory publishers solicit manuscripts through e-mail invitations to potential
      authors, with the goal of enticing authors to submit a manuscript to the journal.
      This descriptive study examined the characteristics of 206 e-mail invitations
      from predatory journals and publishers sent to faculty and students in a school
      of nursing over a 10-week period. Characteristics of these e-mails included use
      of flattering language, due dates for submissions close to the date of the e-mail
      sent, requests for general topics, and awkward phrases. However, many e-mails did
      not have characteristics that clearly identified them as coming from a predatory
      journal or publisher. Education on predatory publishing is needed for all nurse
      authors, specifically how to identify and confirm whether a journal is predatory
      or legitimate. J Contin Educ Nurs. 2018;49(4):171-177.

PMID- 29596705
TI  - Evaluation of a Pain Management Education Program and Operational Guideline on
      Nursing Practice, Attitudes, and Pain Management.
AB  - Nurses lack adequate pain management knowledge, which can result in poorly
      managed postsurgical pain. This study aimed to develop, implement, and evaluate
      pain management education and operational guidelines to improve nursing knowledge
      and pain management. This quality improvement project employed convenience
      samples of surgical oncology nurses and postoperative patients. The intervention
      involved an online module, live education, and operational guideline for pain
      management. Nurses completed pre- and postintervention practice and attitudes
      surveys. Random chart reviews of intravenous narcotic administrations the day
      before discharge were completed to evaluate whether narcotic administration
      changed after intervention. Readmissions and Hospital Consumer Assessment of
      Healthcare Providers and Systems data were collected to determine whether the
      intervention influenced patient satisfaction. A statistically significant
      improvement in nursing practice and intravenous narcotic administrations
      demonstrated changes to pain management practices employed by the nursing staff.
      Although not statistically significant, fewer pain-related readmissions occurred
      postintervention. Findings demonstrate that targeted pain management continuing
      education, paired with operational guidelines, improves nursing practice and
      decreases intravenous narcotic administrations prior to discharge. J Contin Educ
      Nurs. 2018;49(4):178-185.

PMID- 29596706
TI  - Team Teaching in Nursing Education.
AB  - Team teaching is used to describe a broad array of teaching configurations that
      offer benefits to students that cannot be duplicated by a single educator.
      Although articles and books have been written to describe team teaching in other
      fields, little has been written about team teaching in nursing. In a field with
      clinical application, team teaching offers more richness in perspective when
      there are two complimentary educators teaching the content. The opportunity to
      learn from a colleague, while guiding students, is an added benefit of team
      teaching. We are in an era of competition for employees and students, so
      institutions with a reputation for creating a commitment to learning have an
      advantage. Students who have the benefit of a strong team to guide their learning
      are more often positive ambassadors for their institution. The purpose of this
      article is to provide an overview of team teaching as experienced by two nurse
      educators. J Contin Educ Nurs. 2018;49(4):186-192.

PMID- 29596707
TI  - Pilot Study of a Two-Step Delirium Detection Protocol Administered By Certified
      Nursing Assistants, Physicians, and Registered Nurses.
AB  - The feasibility and acceptability of a two-step screening protocol for delirium
      identification was pilot tested. Step 1, a screening tool, comprises two items:
      "Please tell me the day of the week," and "Please tell me the months of the year
      backwards starting with December." If either/both items are incorrect, Step 2, a
      3-minute diagnostic assessment, follows. Trained researchers enrolled 24
      hospitalized older adults and identified 22% to be delirious after a reference
      standard assessment. Thereafter, physicians and RNs completed the two-step
      protocol, whereas certified nursing assistants (CNAs) completed the screener
      only, on the same patients. All three clinical assessments were successfully
      completed in 100% of enrolled participants and within the target 2-hour time
      window in 91%. The screener and two-step protocol achieved high sensitivities and
      specificities in RNs, CNAs, and physicians. Qualitative information on barriers
      to and facilitators of implementation was also collected. Nurses and other
      clinicians can feasibly implement this ultra-brief screener and two-step
      protocol, which holds promise to improve delirium identification. [Journal of
      Gerontological Nursing, 44(5), 18-24.].

PMID- 29596708
TI  - Health Benefits and Risks of Pets in Nursing Homes: A Survey of Facilities in
      Ohio.
AB  - Pets are encountered in nursing homes and although they provide health benefits
      to individuals, they are also a source of health risks. The current study aimed
      to determine the frequency and types of animals in nursing homes, perceived
      benefits, and content of policies addressing health risks. Ninety-five
      administrators from unique nursing homes in Ohio completed an online survey
      addressing perceived benefits and risks of animals and policies in place. Animals
      were permitted in 99% of nursing homes, with dogs (95%), cats (85%), birds (71%),
      fish (55%), and farm animals (40%) most frequently reported. Respondents
      perceived animal interactions resulted in high health benefits for residents.
      Most facilities (70/75; 93%) reported having an animal policy, yet important gaps
      were frequently identified in the content of policies. Most respondents (75%) did
      not report health and safety concerns with animals in facilities. Best practice
      guidelines and policies should be developed and implemented in nursing homes to
      address requirements for different animal ownership models, range of animal
      species, and staff knowledge. [Journal of Gerontological Nursing, 44(5), 39-45.].

PMID- 29596709
TI  - Leadership in Nursing Homes: Directors of Nursing Aligning Practice With
      Regulations.
AB  - Nursing homes use team nursing, with minimal RN presence, leaving the majority of
      direct care to licensed practical/vocational nurses (LPNs/LVNs) and unlicensed
      assistive personnel (UAP), including medication aides. The current article
      describes challenges faced by nursing home directors of nursing (DONs) leading
      and managing a team nursing approach, including consideration of scope of
      practice, delegation and supervision regulations, and related policy
      implications. A secondary data analysis was performed of qualitative data from a
      study to develop and test DON guidelines for delegation in nursing home practice.
      A convenience sample (N = 29) of current or previous DONs and other nursing home
      leaders with knowledge and expertise in the DON role participated in in-depth,
      guided interviews. The findings highlight a core concern to nursing licensure
      policy and regulation: knowledge and practice gaps related to scope of practice
      and delegation and supervision among DONs, RNs, and LPNs/LVNs, as well as
      administrators, and the role of nursing leaders in supporting appropriate
      delegation practices. The findings offer directions for research and practice in
      addressing challenges in aligning team nursing practices with regulatory
      standards as well as the related gaps in knowledge among DONs, administrators,
      and nursing staff. [Journal of Gerontological Nursing, 44(6), 10-14.].

PMID- 29596710
TI  - Telehealth Factors for Predicting Hospital Length of Stay.
AB  - Identifying older adults with heart failure at risk for hospital readmission is
      challenging, and risk prediction models may be improved with inclusion of
      telehealth factors. In the current study, demographic, clinical, telehealth, and
      use data for emergency department (ED) presentations, hospitalizations, and
      length of stay (LOS) were collected from the records of 187 Veterans with heart
      failure participating in a 90-day Care Coordination Home Telehealth program
      between September 2007 and September 2013. Heart failure-related ED visits were
      17.6% and 18.2% required hospitalization with an average LOS of 7 days (range = 1
      to 38 days). Binary logistic regression models failed to predict likelihood of an
      ED presentation or hospitalization. Poisson regression models significantly
      predicted hospital LOS on the factors of telehealth alerts, nurse response to
      alerts, advancing age, and chronic renal disease. Data collected from one
      telehealth program significantly contributed to heart failure-related risk
      prediction models and should be included in future models. [Journal of
      Gerontological Nursing, 44(10), 16-20.].

PMID- 29596712
TI  - Marketing Addiction: The Dark Side of Gaming and Social Media.

PMID- 29596711
TI  - Through the Eyes of Nurse Managers in Long-Term Care: Identifying Perceived
      Competencies and Skills.
AB  - Nurse managers (NMs) in long-term care supervise health care services for
      individuals with high acuity levels and numerous comorbidities. There is minimal
      research identifying NMs' skills and competencies as unit leaders within the long
      term care environment. The current mixed-methods study identified NMs' leadership
      skills and competencies. Nineteen NMs with >=5 years' long-term care management
      experience completed the Nurse Manager Inventory Tool and were individually
      interviewed. They rated their clinical skills at the competent level and their
      financial/strategic management skills at the novice level. All other skill
      categories, including leadership reflective practice, diversity, human resource
      leadership/management, relationship management, performance improvement, and
      problem solving, were rated at a competent level. Emergent interview qualitative
      themes included their visibility on the unit, trial and error learning, a sense
      of "aloneness" due to the absence of other RNs, NM position being a tough job,
      need for peer support, role modeling, and importance of supporting the resident
      through their "final journey." [Journal of Gerontological Nursing, 44(5), 32
      38.].

PMID- 29596713
TI  - Commentary.

PMID- 29596714
TI  - Drugs to Treat Alzheimer's Disease.

PMID- 29596715
TI  - Psychopharmacology for Borderline Personality Disorder.
AB  - Treating individuals with borderline personality disorder (BPD) is a complex and
      challenging process fraught with clinician stigma and bias. Clinically,
      polypharmacy is the most common approach, even though it is more likely to
      produce greater drug-drug adverse effects and interactions than effective
      improvement in symptoms. Currently, there are no approved medications specific
      for the treatment of BPD. The current article reviews the extant literature on
      psychopharmacology and provides treatment recommendations. [Journal of
      Psychosocial Nursing and Mental Health Services, 56(4), 8-11.].

PMID- 29596716
TI  - Untitled by Natalie Thomas.

PMID- 29596717
TI  - Influence of Body Composition and Nutrition Parameters in Handgrip Strength: Are
      There Differences by Sex in Hemodialysis Patients?
AB  - BACKGROUND: Hemodialysis (HD) patients are vulnerable to multiple metabolic and
      nutrition derangements, leading to changes in body composition. Handgrip strength
      (HGS) has been used as a nutrition marker. We aimed to evaluate the relationship
      between HGS and lean tissue mass (LTM) with several parameters in HD patients and
      develop HGS predictive equations. METHODS: Cross-sectional study with 155
      patients in HD treatment for >=3 months. Body composition was assessed through
      bioimpedance spectroscopy. HGS was measured with a hydraulic hand dynamometer.
      Biochemical parameters were evaluated. Data were analyzed by sex. RESULTS: Ninety
      four were men, and mean age was 64.4 +/- 14.7 years. We found positive
      correlation of HGS with LTM, lean tissue index, and body cell mass and negative
      correlation between HGS, age, and overhydration in both sexes. Serum albumin
      level presented a positive correlation and magnesium a negative correlation with
      HGS only in men. The LTM presented a positive correlation with protein intake,
      serum albumin level, and body cell mass and a negative correlation with age in
      both groups. A significant positive correlation with magnesium and a negative
      correlation with overhydration were observed in men. The predictability of the
      models was R2 = 0.618 for men and R2 = 0.500 for women. CONCLUSION: HGS is highly
      correlated with LTM, and both differ between sexes and are, therefore,
      differently correlated with the parameters studied. Body composition,
      overhydration, and some biochemical parameters explain changes in HGS. Predictive
      models including body composition and biochemical parameters may explain at least
      50% of the variance of HGS.

PMID- 29596718
TI  - Bioelectrical Impedance Analysis-Derived Measurements in Chronic Hepatitis C:
      Clinical Relevance of Fat-Free Mass and Phase Angle Evaluation.
AB  - OBJECTIVE: Because cirrhotic patients are at high risk of malnutrition and
      sarcopenia, we evaluated the prevalence of low fat-free mass index (FFMI) and low
      phase angle (PhA) among patients with chronic hepatitis C (CHC). METHODS: In
      total, 135 subjects with CHC (50.4% males; mean age, 52.4 +/- 11.8 years; 65.9%
      noncirrhotic and 34.1% compensated cirrhotic patients) were prospectively
      included and evaluated by bioelectrical impedance analysis. Subjective global
      assessment was used to evaluate malnutrition. RESULTS: Low FFMI and low PhA were
      identified in 21.5% and 23.7% of the patients, respectively. Compensated
      cirrhotic patients had lower PhA values than those without cirrhosis. Low FFMI
      was associated with male sex (odds ratio [OR], 2.74; 95% confidence interval
      [CI], 1.00-7.01; P = .04) and malnutrition (OR, 4.27; 95% CI, 1.42-12.90; P =
      .01). Low PhA was associated with cirrhosis (OR, 3.92; 95% CI, 1.56-9.86; P =
      .004), malnutrition (OR, 5.52; 95% CI, 1.73-17.62; P = .004), and current alcohol
      use (OR, 2.77; 95% CI, 1.01-7.58; P = .05). Reactance (Xc) normalized for height
      (H), an indicator of muscle strength, was independently associated with male sex,
      age, hypertension, and serum albumin. CONCLUSION: Host factors, including
      clinical comorbidities, lifestyle, and nutrition status, are associated with low
      FFMI and low PhA in noncirrhotic and in compensated cirrhotic patients with CHC.
      These findings highlight the relevance of evaluating body composition in patients
      chronically infected by hepatitis C virus independently of the stage of liver
      disease.

PMID- 29596719
TI  - Estimating Resting Energy Expenditure by Different Methods as Compared With
      Indirect Calorimetry for Patients With Pulmonary Hypertension.
AB  - BACKGROUND: For patients with pulmonary hypertension, nutrition status is an
      independent predictor of morbidity and mortality, and energy expenditure can be
      strongly influenced by lung disease. Indirect calorimetry (IC) is the gold
      standard for measuring resting energy expenditure (REE), this study aimed to
      compare the results of REE estimated by different methods with those obtained by
      IC for patients with pulmonary hypertension. METHODS: In this cross-sectional
      study (n = 34), REE was estimated by bioelectrical impedance analysis and the
      predictive equations of Harris-Benedict, Food and Agriculture Organization /
      World Health Organization, Institute of Medicine, Cunningham, Katch-McArdle, and
      Mifflin-St Jeor. RESULTS: Mean patient age was 47.0 +/- 14.5 years, and 76.5%
      were women. REE obtained with IC was strongly correlated with all other
      estimation methods but showed higher mean values: IC 1750.8 +/- 434.3 kcal vs
      bioelectrical impedance analysis, 1549.0 +/- 417.8 kcal; Harris-Benedict, 1493.1
      +/- 337.0 kcal; FAO/WHO, 1536.1 +/- 345.0 kcal; Institute of Medicine, 1457.1 +/-
      293.2 kcal; Cunningham, 1597.3 +/- 292.3 kcal; Katch-McArdle, 1447.7 +/- 287.0
      kcal; and Mifflin-St Jeor, 1388.7 +/- 303.9 kcal. The analysis of agreement
      showed a clinically significant bias of approximately -255 kcal in all estimation
      methods when compared with IC. CONCLUSION: Although there was a strong
      correlation between REE estimation methods and IC, there was no agreement between
      them. All estimation methods underestimated energy needs by about 255 kcal for
      patients with pulmonary hypertension, and the Cunningham equation had the
      smallest difference in relation to IC.

PMID- 29596722
TI  - Commentary: Elders, others and addiction: Do they care and want to understand.

PMID- 29596720
TI  - Differential mobility spectrometry (DMS) reveals the elevation of urinary
      acetylcarnitine in non-human primates (NHPs) exposed to radiation.
AB  - Acetylcarnitine has been identified as one of several urinary biomarkers
      indicative of radiation exposure in adult rhesus macaque monkeys (non-human
      primates, NHPs). Previous work has demonstrated an up-regulated dose-response
      profile in a balanced male/female NHP cohort. As a contribution toward the
      development of metabolomics-based radiation biodosimetry in human populations and
      other applications of acetylcarnitine screening, we have developed a
      quantitative, high-throughput method for the analysis of acetylcarnitine. We
      employed the Sciex SelexIon DMS-MS/MS QTRAP 5500 platform coupled to flow
      injection analysis (FIA), thereby allowing for fast analysis times of less than
      0.5 minutes per injection with no chromatographic separation. Ethyl acetate is
      used as a DMS modifier to reduce matrix chemical background. We have measured NHP
      urinary acetylcarnitine from the male cohorts that were exposed to the following
      radiation levels: control, 2, 4, 6, 7, and 10 Gy. Biological variability, along
      with calibration accuracy of the FIA-DMS-MS/MS method, indicates LOQ of 20 MUM,
      with observed biological levels on the order of 600 MUM and control levels near
      10 MUM. There is an apparent onset of intensified response in the transition from
      6 to 10 Gy. The results demonstrate that FIA-DMS-MS/MS is a rapid, quantitative
      technique that can be utilized for the analysis of urinary biomarker levels for
      radiation biodosimetry.

PMID- 29596723
TI  - Commentary.

PMID- 29596721
TI  - Substance use comorbidity in bipolar disorder: A qualitative review of treatment
      strategies and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Substance use disorders (SUDs) are present in up to
      70% of patients with bipolar disorder (BD) and contribute to high rates of
      disability, morbidity, and treatment non-adherence. Despite this prevalence, few
      trials have investigated targeted psychosocial interventions for comorbid BD and
      SUDs. METHODS: Using PubMed and PsycINFO, we conducted a search of the literature
      up to January 2018 for psychosocial interventions targeted to patients with
      comorbid BD and SUDs. We identified eight total trials. Of these studies, four
      randomized and two open trials targeted the types of substance use (alcohol and
      illicit drugs) of primary concern to mood stability; the remaining two studies,
      both open trials, targeted smoking cessation. RESULTS: None of the randomized
      trials provided consistent evidence for management of both mood symptoms and
      substance use though integrated group therapy (IGT) demonstrated consistent
      beneficial effects on substance use outcomes. Other treatments showed benefit for
      mood symptoms without benefits for alcohol or illicit substance use. Small pilot
      studies of combined treatments for smoking cessation provided some initial
      promise. CONCLUSIONS: At present, IGT is the most-well validated and efficacious
      approach if substance use is targeted in an initial treatment phase. For a
      subsequent phase, additional psychosocial BD treatments may be needed for mood
      and functioning benefits. SCIENTIFIC SIGNIFICANCE: This review synthesizes the
      psychosocial interventions that have been conducted in comorbid BD and SUDs while
      also providing a perspective on which intervention elements are helpful for
      addressing substance use versus mood symptoms in patients with these co-occurring
      conditions. (Am J Addict 2018;27:188-201).

PMID- 29596724
TI  - A randomized controlled trial of a gender-focused addiction model versus 12-step
      facilitation for women veterans.
AB  - BACKGROUND AND OBJECTIVES: Substance use disorder (SUD) has increased among
      women, including military veterans, yet SUD treatment was historically designed
      for males. This randomized controlled trial compared 12 individual sessions of a
      gender-focused SUD recovery model, A Woman's Path to Recovery (WPR) to an
      evidence-based, non-gender-focused SUD model, 12-Step Facilitation (TSF) for 66
      women veterans with current severe SUD. METHODS: The primary outcome was
      substance use; secondary outcomes were associated problems (e.g., psychological);
      coping skills, and 12-step attendance, with assessment at baseline, end-of
      treatment, and 3-month followup. RESULTS: Substance use decreased over time, with
      no difference between conditions. Decreases occurred from baseline to end-of
      treatment and baseline to followup and, for drug severity, also from end-of
      treatment to followup. Effect sizes were large for alcohol and medium otherwise.
      Secondary outcomes were largely consistent with this pattern of improvement.
      Urinalysis/breathalyzer supported self-report. Treatment attendance was 62% for
      WPR and 57% for TSF (not significantly different). Twelve-step group attendance,
      surprisingly, did not increase in either condition. DISCUSSION AND CONCLUSIONS:
      WPR provides a useful addition to women's SUD treatment options, with outcomes no
      different than an established evidence-based model, TSF. Both showed positive
      impact on substance use and related areas. Our lack of differences based on
      gender-focus may reflect women veterans being acculturated to a male military
      environment. Limitations include lack of an untreated control, a sample limited
      to veterans, and use of a large effect size for power assumptions. SCIENTIFIC
      SIGNIFICANCE: This is the first RCT of a gender-focused approach for women
      veterans with SUD. (Am J Addict 2018;27:210-216).

PMID- 29596726
TI  - Case series: Salvia divinorum as a potential addictive hallucinogen.
AB  - BACKGROUND AND OBJECTIVE: Recreational use of salvia divinorum (salvia), a
      potent, naturally occurring hallucinogen, is on the rise internationally. Despite
      the paucity of information about its long-term health effects, salvia is readily
      available and generally portrayed as a safe non-addictive substance. METHODS AND
      RESULTS: We report on two patients who presented with an enduring and pervasive
      pattern of salvia use. DISCUSSION AND CONCLUSIONS: Evaluating patients for salvia
      use during clinical assessment is strongly encouraged, especially among young
      polysubstance users. SCIENTIFIC SIGNIFICANCE: Clinicians should be mindful of the
      multifaceted psychiatric effects of salvia, including the potential for a use
      disorder. (Am J Addict 2018;27:163-165).

PMID- 29596727
TI  - Issue Information - Editorial Board.

PMID- 29596725
TI  - Antagonists in the medical management of opioid use disorders: Historical and
      existing treatment strategies.
AB  - BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) is a chronic condition with
      potentially severe health and social consequences. Many who develop moderate to
      severe OUD will repeatedly seek treatment or interact with medical care via
      emergency department visits or hospitalizations. Thus, there is an urgent need to
      develop feasible and effective approaches to help persons with OUD achieve and
      maintain abstinence from opioids. Treatment that includes one of the three FDA
      approved medications is an evidence-based strategy to manage OUD. The purpose of
      this review is to address practices for managing persons with moderate to severe
      OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention
      treatment. METHODS: Literature available on PubMed was used to review the
      evolution of treatment strategies from the 1960s onward to manage opioid
      withdrawal and initiate treatment with naltrexone. RESULTS: Emerging practices
      for extended-release naltrexone induction include the use of agonist tapers and
      adjuvant medications. Clinical challenges frequently encountered when initiating
      this therapy include managing withdrawal and ongoing opioid use during treatment.
      Clinical factors may inform decisions regarding patient selection and length of
      naltrexone treatment, such as recent opioid use and patient preferences.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Treatment strategies to manage opioid
      withdrawal have evolved, but many patients with OUD do not receive medication for
      the prevention of relapse. Clinical strategies for induction onto extended
      release naltrexone are now available and can be safely and effectively
      implemented in specialty and select primary care settings. ((c) 2018 The Authors.
      The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf
      of The American Academy of Addiction Psychiatry (AAAP);27:177-187).

PMID- 29596729
TI  - Issue Information - ToC.

PMID- 29596728
TI  - A meta-analysis of the association between substance use and emerging adult
      development using the IDEA scale.
AB  - BACKGROUND AND OBJECTIVES: Much debate exists surrounding Arnett's theory of
      emerging adulthood in terms of its breadth and application. Researchers have
      attempted to capture dimensions of emerging adulthood (eg, experimentation,
      negativity/instability, other-focus, self-focus, and feeling in-between) through
      self report assessment, using variations of the Inventory of the Dimensions of
      Emerging Adulthood or IDEA. Results from studies investigating this relationship
      have been mixed. We conducted a meta-analysis on the association between
      substance use and the IDEA. METHOD: Data were extracted to calculate
      correlational associations with substance use as well as typical moderators found
      in the literature. Twelve studies were meta-analyzed. RESULTS: We found small
      associations (range: rho = -.03 to .15; d = .06 to 30) between the IDEA scores
      and substance use. We found higher severity (dependence diagnosis) of
      participants yielded larger associations across all dimensions (rho = .16), and
      proportion of college students to be a subscale-specific moderator
      (experimentation, negativity/instability, other-focus, self-focus, and feeling in
      between). Alcohol use outcomes also provided larger subscale-specific
      associations (experimentation, negativity/instability, other-focus, self-focus).
      CONCLUSIONS: The dimensions of emerging adulthood may be less effective in
      predicting substance use among non-college samples and those studies focusing on
      drug use. Further research should prioritize exploring variation in the
      transition to emerging adulthood among non-college samples and the longitudinal
      associations between IDEA and substance use. SCIENTIFIC SIGNIFICANCE: Important
      contributions include the modest association between IDEA and substance use as
      well as specific participant characteristics that amplify or mitigate the
      association between IDEA and substance use. (Am J Addict 2018;27:166-176).

PMID- 29596730
TI  - Differential diagnoses of diaper dermatitis.
AB  - Diaper dermatitis is the most common contact eczema present in early childhood.
      The main cause is an irritant reaction to urine and feces, which is facilitated
      by the occlusive conditions under the diaper, leading to hyperhydration of the
      stratum corneum (diaper dermatitis). In addition, diaper pressure and friction
      can increase the risk of skin inflammation, which also opens the skin up to other
      irritant agents, allergens, and infectious agents, such as candida albicans.
      However, a variety of diseases are associated with inflammation of the skin in
      the diaper region, therefore the term "diaper dermatitis" is merely descriptive
      and does not reflect anything about the etiopathogenesis. The term diaper
      dermatitis refers only to an inflammation in the diapering area and should not be
      automatically equated with reactions to diapers. Making the correct diagnosis
      requires a thorough examination of the skin in its entirety and a detailed report
      of the patient's medical and family history. Once a specific pattern is
      identified, a precise diagnosis, and an appropriate therapy, can be determined.

PMID- 29596731
TI  - Prevention and treatment of diaper dermatitis.
AB  - Diaper dermatitis (DD) is one of the most common skin conditions that infants
      suffer from and their caregivers manage in the first months post-birth. As such,
      questions of effective prevention and treatment of the condition often arise.
      Nonmedical skincare practices that support healthy skin barrier function can
      prevent DD manifestation or alleviate the condition in many cases. The usage of
      barrier emollients and improved diaper technology contributes to keeping moisture
      and irritants away from an infant's delicate skin. This paper addresses facts
      behind commonly asked questions from caregivers regarding DD and discusses
      effective measures to prevent and treat the condition.

PMID- 29596732
TI  - Introduction: Hot topics in neonatal skin care from the 13th World Congress of
      Pediatric Dermatology (Chicago, IL - July 6-9, 2017).

PMID- 29596733
TI  - Skin barrier in the neonate.
AB  - The purpose of this review is to focus on determinants of skin barrier function
      in neonates at molecular and cellular levels. The skin barrier is critical in
      terms of water and gas exchanges during fetal life and undergoes rapid changes at
      birth, followed by a progressive maturation. Consequences of skin barrier
      disruption can be extremely detrimental or lethal, as shown in severe genetic
      epidermal defects. In this context, the fine-tuned rapid adaptation from a liquid
      to a gaseous milieu is not fully understood. The stratum corneum provides an air
      liquid barrier, tight junctions in the granular layer provide a liquid-liquid
      barrier, aquaporins represent a plumbing system for water-glycerol as well as gas
      exchanges, and Langerhans cells are central to the immunological barrier. Acid
      mantle formation is essential for appropriate interaction between the skin and
      microbial symbionts. Temperature and pH regulate the key enzyme activities
      responsible for the integrity of the stratum corneum. Skin barrier permeability
      can be assessed noninvasively and simply with miniaturized devices measuring
      transepidermal water loss, where water flow is faster in cases of a damaged or
      functionally premature barrier. New avenues for therapeutic skin barrier research
      in neonates include a better delineation of the maturation of aquaporins in water
      balance and gas exchanges from fetal to neonatal life and a better understanding
      of the role of vernix caseosa, in particular, for the implantation of a healthy
      microbiote. Practical applications should be derived for caring for infant skin,
      particularly in fragile zones, such as the diaper area.

PMID- 29596734
TI  - The American College of Rheumatology is Launching an Open Access Journal and
      Seeking an Editor-in-Chief.

PMID- 29596735
TI  - Dennis Luke Murphy, M.D. (1936-2017).

PMID- 29596736
TI  - G2B reviews: Epigenetics, epitranscriptomics, microRNAs and more: Emerging
      approaches to the study of genes, brain and behavior.

PMID- 29596737
TI  - Erratum.

PMID- 29596738
TI  - Erratum.

PMID- 29596739
TI  - In Situ Forming, Cytocompatible, and Self-Recoverable Tough Hydrogels Based on
      Dual Ionic and Click Cross-Linked Alginate.
AB  - A dual cross-linking strategy was developed to answer the urgent need for fatigue
      resistant, cytocompatible, and in situ forming tough hydrogels. Clickable, yet
      calcium-binding derivatives of alginate were synthesized by partial substitution
      of its carboxyl functionalities with furan, which could come into Diels-Alder
      click reaction with maleimide end groups of a four arm poly(ethylene glycol)
      cross-linker. Tuning the cooperative viscoelastic action of transient ionic and
      permanent click cross-links within the single network of alginate provided a soft
      tough hydrogel with a set of interesting features: (i) immediate self-recovery
      under cyclic loading, (ii) highly efficient and autonomous self-healing upon
      fracture, (iii) in situ forming ability for molding and minimally invasive
      injection, (iv) capability for viable cell encapsulation, and (v) reactivity for
      on-demand biomolecule conjugation. The facile strategy is applicable to a wide
      range of natural and synthetic polymers by introducing the calcium binding and
      click reacting functional groups and can broaden the use of tough hydrogels in
      load-bearing, cell-laden applications such as soft tissue engineering and
      bioactuators.

PMID- 29596740
TI  - Formation of Particulate Matter from the Oxidation of Evaporated Hydraulic
      Fracturing Wastewater.
AB  - The use of hydraulic fracturing for production of petroleum and natural gas has
      increased dramatically in the past decade, but the environmental impacts of this
      technology remain unclear. Experiments were conducted to quantify airborne
      emissions from 12 samples of hydraulic fracturing flowback wastewater collected
      in the Permian Basin, as well as the photochemical processing of these emissions
      leading to the formation of particulate matter (PM). The concentration of total
      volatile carbon (hydrocarbons evaporating at room temperature) averaged 29 mg of
      carbon per liter. After photochemical oxidation under high NO x conditions, the
      amount of organic PM formed per milliliter of wastewater evaporated averaged 24
      MUg; the amount of ammonium nitrate formed averaged 262 MUg. Based on the mean PM
      formation observed in these experiments, the estimated formation of PM from
      evaporated flowback wastewater in the state of Texas is in the range of estimated
      PM emissions from diesel engines used in oil rigs. Evaporation of flowback
      wastewater, a hitherto unrecognized source of secondary pollutants, could
      significantly contribute to ambient PM concentrations.

PMID- 29596741
TI  - Cell-Free Optogenetic Gene Expression System.
AB  - Optogenetic tools provide a new and efficient way to dynamically program gene
      expression with unmatched spatiotemporal precision. To date, their vast potential
      remains untapped in the field of cell-free synthetic biology, largely due to the
      lack of simple and efficient light-switchable systems. Here, to bridge the gap
      between cell-free systems and optogenetics, we studied our previously engineered
      one component-based blue light-inducible Escherichia coli promoter in a cell-free
      environment through experimental characterization and mathematical modeling. We
      achieved >10-fold dynamic expression and demonstrated rapid and reversible
      activation of the target gene to generate oscillatory response. The deterministic
      model developed was able to recapitulate the system behavior and helped to
      provide quantitative insights to optimize dynamic response. This in vitro
      optogenetic approach could be a powerful new high-throughput screening technology
      for rapid prototyping of complex biological networks in both space and time
      without the need for chemical induction.

PMID- 29596742
TI  - Intramolecular Aryne-Furan Cycloadditions for the Synthesis of Anticancer
      Naphthalimides.
AB  - An intramolecular aryne Diels-Alder reaction with a furan moiety was applied to
      the synthesis of dihydrobenzo[ de]isochromenes as intermediates toward
      naphthalimides. After oxidation, this method offers an efficient approach for the
      synthesis of substituted naphthalimides, which showed potent cytotoxic activity
      against HT-29 human cancer cell line.

PMID- 29596743
TI  - Visible-Light-Driven Alkyne Hydro-/Carbocarboxylation Using CO2 via
      Iridium/Cobalt Dual Catalysis for Divergent Heterocycle Synthesis.
AB  - We present herein the first visible-light-driven hydrocarboxylation as well as
      carbocarboxylation of alkynes using CO2 via an iridium/cobalt dual catalysis.
      Such transformations provide access to various pharmaceutically important
      heterocycles in a one-pot procedure from readily available alkynes. Coumarins, 2
      quinolones, and 2-benzoxepinones were directly accessed through a one-pot alkyne
      hydrocarboxylation/alkene isomerization/cyclization sequence in which the Ir
      photocatalyst serves a dual role to promote single-electron transfer in alkyne
      hydrocarboxylation and energy transfer in the subsequent alkene isomerization.
      Moreover, an unprecedented cobalt carboxylation/acyl migration cascade enables
      alkyne difunctionalization to introduce gamma-hydroxybutenolides with high
      efficiency. We expect that this cascade strategy will inspire new perspectives
      for alkyne and alkene difunctionalization.

PMID- 29596744
TI  - CADS: CRISPR/Cas12a-Assisted DNA Steganography for Securing the Storage and
      Transfer of DNA-Encoded Information.
AB  - Because DNA has the merit of high capacity and complexity, DNA steganography,
      which conceals DNA-encoded messages, is very promising in information storage.
      The classical DNA steganography method hides DNA with a "secret message" in a
      mount of junk DNA, and the message can be extracted by polymerase chain reaction
      (PCR) using specific primers (key), followed by DNA sequencing and sequence
      decoding. As leakage of the primer information may result in message insecurity,
      new methods are needed to better secure the DNA information. Here, we develop a
      pre-key by either mixing specific primers (real key) with nonspecific primers
      (fake key) or linking a real key with 3'-end redundant sequences. Then, the
      single-stranded DNA (ssDNA) trans cleavage activity of CRISPR/Cas12a is employed
      to cut a fake key or remove the 3'-end redundant sequences, generating a real key
      for further information extraction. Therefore, with the Cas12a-assisted DNA
      steganography method, both storage and transfer of DNA-encoding data can be
      better protected.

PMID- 29596746
TI  - Noncovalent Interactions Descriptor Based on the Source Function of Individual
      Localized Molecular Orbitals in Whole Space.
AB  - The partitioning of total electron density into localized molecular orbitals
      (LMOs) within the source function framework is presented as an exploit useful to
      the characterization of noncovalent interactions. The resulting approach uses
      only a converged LMO base as input and does not require grid data handling or
      numerical integration, making it viable for the study of large systems. Tests
      conducted on a series of prototypical hydrogen and halogen bonds demonstrate that
      this descriptor retrieves chemically intuitive interaction motifs beyond the
      classical two-center picture. Advantages and disadvantages of different
      localization schemes are discussed in terms of their peculiar description of
      sigma-pi mixing and in terms of their inherent basis set dependence.

PMID- 29596745
TI  - Imidazopyrazinones (IPYs): Non-Quinolone Bacterial Topoisomerase Inhibitors
      Showing Partial Cross-Resistance with Quinolones.
AB  - In our quest for new antibiotics able to address the growing threat of multidrug
      resistant infections caused by Gram-negative bacteria, we have investigated an
      unprecedented series of non-quinolone bacterial topoisomerase inhibitors from the
      Sanofi patrimony, named IPYs for imidazopyrazinones, as part of the Innovative
      Medicines Initiative (IMI) European Gram Negative Antibacterial Engine (ENABLE)
      organization. Hybridization of these historical compounds with the
      quinazolinediones, a known series of topoisomerase inhibitors, led us to a novel
      series of tricyclic IPYs that demonstrated potential for broad spectrum activity,
      in vivo efficacy, and a good developability profile, although later profiling
      revealed a genotoxicity risk. Resistance studies revealed partial cross
      resistance with fluoroquinolones (FQs) suggesting that IPYs bind to the same
      region of bacterial topoisomerases as FQs and interact with at least some of the
      keys residues involved in FQ binding.

PMID- 29596747
TI  - Water Adsorption on Clean and Defective Anatase TiO2 (001) Nanotube Surfaces: A
      Surface Science Approach.
AB  - We use ab initio molecular dynamics simulations to study the adsorption of thin
      water films with 1 and 2 ML coverage on anatase TiO2 (001) nanotubes. The
      nanotubes are modeled as 2D slabs, which consist of partially constrained and
      partially relaxed structural motifs from nanotubes. The effect of anion doping on
      the adsorption is investigated by substituting O atoms with N and S impurities on
      the nanotube slab surface. Due to strain-induced curvature effects, water adsorbs
      molecularly on defect-free surfaces via weak bonds on Ti sites and H bonds to
      surface oxygens. While the introduction of an S atom weakens the interaction of
      the surface with water, which adsorbs molecularly, the presence of an N impurity
      renders the surface more reactive to water, with a proton transfer from the water
      film and the formation of an NH group at the N site. At 2 ML coverage, a further
      surface-assisted proton transfer takes place in the water film, resulting in the
      formation of an OH- group and an NH2+ cationic site on the surface.

PMID- 29596748
TI  - Stereospecific Ring Contraction of Bromocycloheptenes through Dyotropic
      Rearrangements via Nonclassical Carbocation-Anion Pairs.
AB  - Experimental and theoretical evidence is reported for a rare type I dyotropic
      rearrangement involving a [1,2]-alkene shift, leading to the regio- and
      stereospecific ring contraction of bromocycloheptenes. This reaction occurs under
      mild conditions, with or without a Lewis acid catalyst. DFT calculations show
      that the reaction proceeds through a nonclassical carbocation-anion pair, which
      is crucial for the low activation barrier and enantiospecificity. The chiral
      cyclopropylcarbinyl cation may be a transition state or an intermediate,
      depending on the reaction conditions.

PMID- 29596749
TI  - Synthesis and Characterization of Temperature-Sensitive and Chemically Cross
      Linked Poly( N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in
      Photodynamic Therapy.
AB  - A novel poly( N-isopropylacrylamide) (PNIPAM) hydrogel containing different
      photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and
      protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a
      significant improvement in water solubility and potential for PDT applications
      compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and
      PpIX-DME to the poly( N-isopropylacrylamide) chain was achieved using the
      dispersion polymerization method. This study describes how the use of
      nanohydrogel structures to deliver a photosensitizer with low water solubility
      and high aggregation tendencies in polar solvents overcomes these limitations. FT
      IR spectroscopy, UV-vis spectroscopy, 1H NMR, fluorescence spectroscopy, SEM, and
      DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels.
      Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers
      are covalently conjugated to the polymer chains, which prevents aggregation and
      thus allows significant singlet oxygen production upon illumination. Likewise,
      the lower critical solution temperature was raised to ~44  degrees C in the new
      PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with >90% cell
      viability even at high concentrations of the photosensitizer in vitro.
      Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based
      nanohydrogel in the nanomolar range and a more modest, but significant,
      photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest
      that the new hydrogels have potential for applications in photodynamic therapy.

PMID- 29596750
TI  - Ray Tracing for Fluence Rate Simulations in Ultraviolet Photoreactors.
AB  - The performance of photochemical reactors is governed by the spatial distribution
      of radiant energy within the irradiated region of the reactor. Ray tracing has
      been widely used for simulation of lighting systems. The central hypothesis of
      this work was that ray tracing can provide accurate simulations of fluence rate
      fields within ultraviolet (UV) photoreactors by accounting for the physical and
      optical phenomena that will govern fluence rate fields in UV photoreactors. Ray
      tracing works by simulating the behavior of a large population of rays emanating
      from a radiation source to describe the spatial distribution of radiant energy
      (i.e., fluence rate) within a system. In this study, fluence rate calculations
      were performed using commercial ray tracing software for three basic UV reactors,
      each with a single low-pressure Hg lamp. Fluence rate calculations in the ray
      tracing program were based on the formal definition of fluence rate, calculated
      as the incident radiant power from all directions on a small spherical receptor,
      divided by the cross-sectional area of that sphere. The results of this study
      demonstrate that ray tracing can provide predictions of fluence rate in UV
      radiative systems that are close to experimental measurements and the predictions
      of other numerical methods.

PMID- 29596751
TI  - Breastfeeding Versus Bottle Feeding on Malocclusion in Children: A Meta-Analysis
      Study.
AB  - BACKGROUND: Breastfeeding plays an important role in child health. However, there
      are doubts about its influence on malocclusions. Systematic reviews have yielded
      contradictory results. Research aim: This study aimed to investigate whether the
      type and duration of breastfeeding are associated with malocclusions in primary
      teething. METHODS: The review strategy included several electronic databases,
      lists of references, reviews, dissertation and thesis websites, experts, and
      other relevant documents. Published and unpublished observational studies ( N =
      42) were reviewed using the Participants (children), Interventions
      (breastfeeding), Comparisons (bottle feeding), Outcomes (malocclusion), and Study
      design (observational) strategy, without restrictions on language or locale.
      Information about the authors, publication year, country of study, setting, study
      design, sample size, age, type and duration of exclusive and mixed breastfeeding,
      and malocclusions was recorded by two blinded evaluators. Quantitative meta
      analysis ( N = 30) of the studies with available data was performed. RESULTS:
      Breastfeeding was a protective factor against malocclusions. The odds of
      association increased with breastfeeding duration. Irrespective of duration,
      breastfeeding had a protective association with open bite. For those who were
      breastfed for up to 6 months, breastfeeding protected against overjet, open bite,
      posterior crossbite, and crowding. Breastfeeding for 12 months or longer was
      associated with lower odds of overjet, open bite, and posterior crossbite.
      Breastfeeding exclusively for 6 months was also a protective factor against
      malocclusions. However, studies on this subject presented low quality,
      statistical heterogeneity, and only unadjusted measures of association in most of
      the cases. CONCLUSION: Breastfeeding beneficially affects primary occlusion when
      practiced for at least 6 months.

PMID- 29596752
TI  - The Next 25 Years of Obstructive Sleep Apnea Epidemiology-Don't Keep Repeating
      Past Mistakes.

PMID- 29596753
TI  - Reply to Holley and Phillips: The Next 25 Years of Obstructive Sleep Apnea
      Epidemiology-Don't Keep Repeating Past Mistakes.

PMID- 29596754
TI  - Severe Periodontitis Is Associated with Myocardial Infarction in Females.
AB  - The aim of the present study was to test the hypothesis that there is a sex
      difference in the association between periodontitis (PD) and a first myocardial
      infarction (MI). The analysis in the case-control study was based on 785 patients
      (147 females and 638 males) with a first MI and 792 matched controls (147 females
      and 645 males), screened for cardiovascular risk factors and subjected to a
      panoramic dental X-ray. Periodontal status was defined by alveolar bone loss and
      diagnosed as no PD (>=80% remaining alveolar bone), mild to moderate PD (66% to
      79%), or severe PD (<66%). Logistic regression was used when analyzing PD as a
      risk factor for MI, adjusting for age, smoking, diabetes, education, and marital
      status. The mean age was 64 +/- 7 y for females and 62 +/- 8 y for males. Severe
      PD was more common in female patients than female controls (14 vs. 4%, P =
      0.005), with an increased risk for severe PD among female patients with a first
      MI (odds ratio [OR] = 3.92, 95% confidence interval [CI] =1.53 to 10.00, P =
      0.005), which remained (OR = 3.72, 95% CI = 1.24 to 11.16, P = 0.005) after
      adjustments. Male patients had more severe PD (7% vs. 4%; P = 0.005) than male
      controls and an increased risk for severe PD (OR = 1.88, 95% CI = 1.14 to 3.11, P
      = 0.005), but this association did not remain following adjustment (OR = 1.67,
      95% CI = 0.97 to 2.84, NS). Severe PD was associated with MI in both females and
      males. After adjustments for relevant confounders, this association did, however,
      remain only in females. These data underline the importance of considering poor
      dental health when evaluating cardiovascular risk, especially in females.

PMID- 29596755
TI  - Association Between Intimate Partner Violence and Breastfeeding Duration: Results
      From the 2004-2014 Pregnancy Risk Assessment Monitoring System.
AB  - BACKGROUND: Intimate partner violence is a major public health problem that
      disproportionately affects women. Current literature investigating the
      relationship between intimate partner violence and breastfeeding is inconsistent.
      Research aim: This study aims to investigate the relationship between physical
      intimate partner violence that occurs in the preconception or prenatal period and
      any breastfeeding duration. METHODS: Data from the retrospective, cross-sectional
      2004-2014 Pregnancy Risk Assessment Monitoring System were analyzed ( N =
      195,264). The outcome, breastfeeding duration, was categorized as never
      breastfed, breastfed 8 weeks or less, and breastfeed more than 8 weeks.
      Multinomial logistic regression was used to obtain crude and adjusted odds ratios
      and 95% confidence intervals. RESULTS: Approximately 6% ( n = 11,766) of survey
      respondents reported preconception and/or prenatal intimate partner violence, and
      36.3% ( n = 67,667) of women reported never breastfeeding. The odds of
      discontinuing breastfeeding before 8 weeks were 18% higher among women who
      reported experiencing abuse 12 months before pregnancy compared with women who
      did not report intimate partner violence (adjusted odds ratio = 1.18; 95%
      confidence interval [1.01, 1.37]). All other estimates showed an overlapping 95%
      confidence interval. CONCLUSION: Breastfeeding is essential in improving maternal
      and child health; however, women in abusive relationships may face additional
      barriers to breastfeeding. Further research is needed to better understand the
      impact of violence on breastfeeding behaviors to inform healthcare practices and
      interventions.

PMID- 29596756
TI  - Validation of the Chinese Version of the Australian Breastfeeding Attitude
      Questionnaire.
AB  - BACKGROUND: The Australian Breastfeeding Knowledge and Attitude Questionnaire
      Short Form (ABKAQ-SF) was designed to measure breastfeeding knowledge and
      attitudes of health professionals. To date, a Chinese version of the attitude
      component of the ABKAQ-SF (ABAQ) is not yet available and has not been cross
      validated with nursing students. Research aims: This study aimed to examine (a)
      the psychometric properties of the ABAQ and (b) group differences and
      responsiveness of the revised 12-item ABAQ (ABAQ12) among nursing students in
      Taiwan. METHODS: Using a cross-sectional two-cohort study design, nursing
      students in Years 2 and 3 of a 4-year bachelor of nursing program ( N = 205)
      completed the Chinese version of the ABAQ, translated using forward and backward
      translations. Content validity, internal consistency reliability, construct
      validity, group differences, and responsiveness of the Chinese version of the
      ABAQ were assessed. RESULTS: Using the principal axis factoring procedure of
      exploratory factor analysis to examine the dimensionality of the ABAQ, a one
      component structure was identified. Six items were deleted, based on the average
      interitem correlation (< 0.2), low corrected item-total correlation (< 0.35), and
      low factor loading (< 0.3). Confirmatory factor analysis of the ABAQ12 supported
      a one-factor solution, with good overall model fit (goodness-of-fit index =
      0.949, Tucker-Lewis index = 0.951, comparative fit index = 0.965, root mean
      square error of approximation = 0.042). Responsiveness of the ABAQ12 scores
      indicated a positive change in breastfeeding attitude between the pre- and
      postclinical placement period. CONCLUSION: The Chinese version of the ABAQ12 is
      valid, reliable, and responsive and is suitable for assessing the breastfeeding
      attitudes of nursing students in the Taiwanese higher education settings.

PMID- 29596758
TI  - Social Justice and Lactation.

PMID- 29596759
TI  - Breastfeeding, Antidepressants, and Depression in the Mercy Pregnancy and
      Emotional Well-Being Study.
AB  - BACKGROUND: Depression is consistently shown to predict lower rates of
      breastfeeding. In a handful of studies, breastfeeding has predicted lower
      depression symptoms. However, studies demonstrating the latter are limited in
      their measurement of both depression and breastfeeding and have not followed
      participants from pregnancy across the postpartum period. Research Aim: The
      primary aim of this study was to describe breastfeeding intentions and behaviors
      for the first 12 months postpartum among nonmedicated depressed, antidepressant
      exposed, and control participants. The secondary aim was to examine group
      differences in the association between depressive symptoms and breastfeeding
      duration up to 12 months postpartum. METHODS: First-trimester women ( n = 212)
      were recruited into a prospective longitudinal study. Depressive disorders at
      baseline were diagnosed using the Structured Clinical Interview for DSM-IV Axis I
      Disorders, and depressive symptoms were measured at the first and second
      trimesters and 6 and 12 months postpartum using the Edinburgh Postnatal
      Depression Scale. Breastfeeding duration, support from family and employers, and
      perceptions of participants' experience were measured. RESULTS: Depressed women
      and antidepressant-exposed women reported a trend toward lower rates of
      intention, initiation, and duration, but this did not reach statistical
      significance. There was a statistically significant difference on depressive
      symptoms for women taking antidepressants during pregnancy, compared with
      controls, when they continued to breastfeed for 12 months postpartum.
      CONCLUSIONS: This study did not find a strong association between depression or
      antidepressant use and intention to breastfeed, partner breastfeeding support, or
      initiation or duration of breastfeeding. However, for women who took
      antidepressants, there was evidence that breastfeeding for 12 months was
      associated with lower depressive symptoms.

PMID- 29596760
TI  - Precision Modeling of Pulmonary Hypertension Pathology with Induced Pluripotent
      Stem Cell-derived Cells.

PMID- 29596761
TI  - Vitamin D and the Breastfeeding Infant: Family Medicine Clinicians' Knowledge,
      Attitudes, and Practices.
AB  - BACKGROUND: The American Academy of Pediatrics and the National Academy of
      Medicine recommend vitamin D supplementation for breastfeeding infants. However,
      compliance with this recommendation is poor. Maternal supplementation with
      vitamin D is a safe and effective alternative to achieving vitamin D sufficiency
      in breastfeeding infants, and mothers have indicated a preference for self
      supplementation over infant supplementation. Research aim: We sought to explore
      Family Medicine clinicians' knowledge, attitudes, and practices regarding vitamin
      D supplementation recommendations for breastfeeding dyads. METHODS: Fifty-six
      Family Medicine clinicians (including faculty physicians, resident physicians,
      and nurse practitioners/physician assistants) completed an online, anonymous
      survey regarding their knowledge and practices concerning vitamin D
      supplementation for breastfeeding infants. RESULTS: The vast majority of
      clinicians (92.9%) correctly identified the American Academy of Pediatrics' 2008
      recommended dose for vitamin D supplementation in breastfeeding infants and
      estimated recommending vitamin D supplementation of exclusively breastfeeding
      infants 70.1% of the time. If all options were equivalent, clinicians would
      prefer to offer maternal or infant supplementation (50%) or maternal
      supplementation (37.5%) over infant supplementation (12.5%). Most (69.6%)
      preferred daily over monthly supplementation regimens. CONCLUSION: Family
      Medicine clinicians are knowledgeable regarding current recommendations for
      vitamin D supplementation in breastfeeding infants. They are also open to
      recommending maternal supplementation or offering parents a choice of maternal or
      infant vitamin supplementation.

PMID- 29596762
TI  - ILCA News: Elevating Education to Achieve Knowledge, Equity, and Diversity on a
      Global Platform.

PMID- 29596763
TI  - Breastfeeding in the Community: Addressing Disparities Through Policy, Systems,
      and Environmental Changes Interventions.

PMID- 29596764
TI  - The Role of Medical Students in Short-Term Experiences in Global Health: A
      Perspective from Sao Tome Island.

PMID- 29596765
TI  - Medicine and its Preventive Excesses.

PMID- 29596766
TI  - [Bacteriuria. Cochrane Database Syst Rev. 2015;4:CD009534.]
AB  - Asymptomatic bacteriuria is frequently detected in women aged up to 60 years,
      patients with diabetes and elderly patients. The benefit of antibiotic treatment
      for this condition is controversial. The objective of this Cochrane systematic
      review was to assess the effectiveness and safety of antibiotic treatment for
      asymptomatic bacteriuria in adults. A systematic review of the literature up to
      24 February 2015 was performed using the Cochrane Renal Group's Specialised
      Register. Randomised controlled trials (RCTs) and quasirandomised controlled
      trials comparing antibiotics to placebo or no treatment for asymptomatic
      bacteriuria in adults were included. The outcomes of interest were the
      development of symptomatic urinary tract infection, complications, death, adverse
      events, development of antibiotic resistance, bacteriological cure, and decline
      in kidney function. Nine studies (1614 participants) were included in this
      review. The incidence of symptomatic urinary tract infection, complications or
      death was similar between groups. Antibiotic use was significantly associated
      with bacteriological cure and an increase in minor adverse events. No decline in
      kidney function was observed with any one of the treatments. According to the
      results of the studies included in this revision, authors have concluded that
      there is no clinical benefit in treating asymptomatic bacteriuria in adults.

PMID- 29596767
TI  - Challenges of Ageing in Portugal: Data from the EpiDoC Cohort.
AB  - INTRODUCTION: Portuguese adults have a long lifespan, but it is unclear whether
      they live a healthy life in their final years. We aimed to determine the
      prevalence of multimorbidity and characterize lifestyle and other health outcomes
      among older Portuguese adults. MATERIAL AND METHODS: We performed a cross
      sectional evaluation of 2393 adults, aged 65 and older, during the second wave of
      follow-up of the EpiDoC cohort, a population-based study involving long-term
      follow-up of a representative sample of the Portuguese population. Subjects
      completed a structured questionnaire during a telephone interview. Socioeconomic,
      demographic, lifestyle behaviours, chronic diseases, and health resources
      consumption were assessed. Cluster analysis was done to identify dietary
      patterns. Descriptive and analytic analysis was performed to estimate
      multimorbidity prevalence and its associated factors. RESULTS: Multimorbidity
      prevalence among older adults was 78.3%, increased with age strata (72.8% for 65 
      69 years to 83.4% for >= 80 years), and was highest in Azores (84.9%) and
      Alentejo (83.6%). The most common chronic diseases were hypertension (57.3%),
      rheumatic disease (51.9%), hypercholesterolemia (49.4%), and diabetes (22.7%).
      Depression symptoms were frequent (11.8%) and highest in the oldest strata. The
      mean health-related quality of life (EQ-5D-3L) score was 0.59 +/- 0.38.
      Hospitalization in the previous 12 months was reported by 25.8% of individuals.
      Overall, 66.6% of older adults were physically inactive. 'Fruit and vegetables
      dietary pattern' was followed by 85.4% of individuals; however, regional
      inequalities were found (69% in Azores). Obesity prevalence was 22.3% overall and
      was highest among Azoreans (33%). CONCLUSION: The high prevalence of
      multimorbidity, combined with unhealthy lifestyle behaviours, suggests that the
      elderly populationconstitutes a vulnerable group warranting dedicated
      intervention.

PMID- 29596768
TI  - Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog): Normative
      Data for the Portuguese Population.
AB  - INTRODUCTION: The Alzheimer's Disease Assessment Scale - Cognitive Subscale is a
      brief battery developed to assess cognitive functioning in Alzheimer's disease
      that encompasses the core characteristics of cognitive decline (e.g. memory,
      language, praxis, constructive ability and orientation). The early detection, as
      well as the monitoring of cognitive decline along disease progression, is
      extremely important in clinical care and interventional research. The main goals
      of the present study were to analyze the psychometric properties of the
      Portuguese version of the Alzheimer's Disease Assessment Scale - Cognitive
      Subscale, and to establish normative values for the Portuguese population.
      MATERIAL AND METHODS: The Portuguese version of Alzheimer's Disease Assessment
      Scale - Cognitive Subscale was administered to 223 cognitively healthy
      participants according to a standard assessment protocol consisting of the Mini
      Mental State Examination, the Montreal Cognitive Assessment and the Adults and
      Older Adults Functional Assessment Inventory. Normal performance on the
      assessment protocol was the inclusion criteria for the study. RESULTS: The
      Alzheimer's Disease Assessment Scale - Cognitive Subscale revealed good
      psychometric properties when used in the Portuguese population. Age was the main
      predictor of the Alzheimer's Disease Assessment Scale - Cognitive Subscale total
      score (R2 = 0.123), whereas the influence of education level was lower (R2 =
      0.027). These two variables explained 14.4% of the variance on the Alzheimer's
      Disease Assessment Scale - Cognitive Subscale scores and were used to stratify
      the normative values for the Portuguese population presented here. CONCLUSION: On
      the total sample, the average total score in the Alzheimer's Disease Assessment
      Scale - Cognitive Subscale was 6 points. The normative data were determined
      according to age and educational level as these were the sociodemographic
      variables that significantly contributed to the prediction of the Alzheimer's
      Disease Assessment Scale - Cognitive Subscale total scores, explaining 14.4% of
      their variance. The normative data are of the utmost importance to ensure proper
      use of this battery in Portugal.

PMID- 29596769
TI  - [Smoking Cessation after Bladder Cancer Diagnosis].
AB  - INTRODUCTION: Smoking is an important risk factor for the development, recurrence
      and progression of bladder cancer. Our aim was to analyze smoking habits after
      diagnosis in bladder cancer patients. Additionally, we evaluated patient
      knowledge about smoking as a risk factor and the urologist role in promoting
      abstinence. MATERIAL AND METHODS: A cross-sectional, observational and
      descriptive study was performed in bladder cancer patients, diagnosed between
      January 2013 and September 2015 (n = 160) in Braga Hospital, in Portugal.
      RESULTS: Smoking history was present in 71.9% of the sample, with 21.9% current
      smokers, (40.7% of abstinence after diagnosis). Smoking was acknowledged as a
      risk factor by 74.4% of the sample, with only 51.3% of ever smokers and 24.4% of
      non-smokers recognizing smoking as the leading risk factor (p = 0.008). The
      presence of other household smokers were significantly higher in patients who
      continued smoking (40%) than in ex-smokers after diagnosis (4.2%) (p = 0.005).
      The majority of smokers at diagnosis (83.1%) were advised to quit by their
      urologist, but only one smoker (1.7%) was offered any specific intervention to
      aid in cessation. DISCUSSION: Smoking is not recognized as the leading risk
      factor for bladder cancer. This limited awareness, associated with the known
      difficulties in quitting smoking and the observed lack of smoking cessation
      interventions, may account for the high current smoking prevalence, albeit in
      line with other studies. CONCLUSION: This study highlights the need for efficient
      smoking cessation programs directed to bladder cancer patients.

PMID- 29596770
TI  - Children Who Leave the Emergency Department Without Being Seen: Why Did They
      Leave and What Would Make Them Stay?
AB  - INTRODUCTION: Children who visit emergency departments and leave without being
      seen represent a multifactorial problem. We aimed to compare the sociodemographic
      characteristics of children who left and of those who did not leave, as well as
      to evaluate parental reasoning, subsequent use of medical care and patient
      outcome. MATERIAL AND METHODS: This was a prospective case-control study of a
      random sample of children who left without being seen and their matched controls
      from an emergency department during a three-month period. We performed a phone
      questionnaire to obtain information concerning reasons for leaving, patient
      outcomes and general feedback. RESULTS: During the study period, 18 200 patients
      presented to the emergency department, of whom 92 (0.5%) left without being seen.
      Fifty-five (59.8%) completed the questionnaire and there were 82 controls. The
      most common reasons for leaving were 'excessive waiting time' (92.7%) and
      'problem could wait' (21.8%). A significantly higher number of patients who left
      sought further medical care (78.2% vs 11%) but they did not experience higher
      levels of unfavourable outcomes. DISCUSSION: The waiting time seems to be the
      major factor that drives the decision to leave. The fact that parents felt safe
      in leaving and the low level of adverse outcomes highlights the low-acuity nature
      of the majority of patients who leave. CONCLUSION: Reducing the waiting times may
      be the logical strategic mean to decrease the rates of patients who leave without
      being seen. However, our data seems to indicate that the concerns surrounding
      clinical outcome after leaving may be partly unwarranted.

PMID- 29596771
TI  - [The Road towards the Responsible and Safe Legalization of Cannabis Use in
      Portugal].
AB  - INTRODUCTION: Recently, the world has seen examples of the legalization of
      cannabis for recreational purposes. Due to the diversity of experiences in
      progress, it is urgent to analyze the impacts of this legalization, from a public
      health perspective. Therefore, this article aims to review the accumulated
      knowledge in the states and countries where the use of cannabis is legal and to
      ponder over the relevance of starting a similar path towards legalization in
      Portugal, thus supporting political decisions to be properly informed and
      evidence-based. MATERIAL AND METHODS: An extensive literature review was
      performed using databases and scientific journals, such as PubMed, as well as the
      search of institutional documentation, including the EMCDDA and SICAD. RESULTS:
      The gathered information provided insights and enabled assessment of (1) the
      acute and chronic effects of cannabis use on health, (2) the Portuguese situation
      related to cannabis and (3) the processes and lessons learned after the
      legalization of cannabis in other countries or states. Given the above, and
      according to the data presented, the authors argue for a safe and responsible
      strategy towards the legalization of cannabis use in Portugal. In accordance, a
      set of concrete proposals are presented. DISCUSSION: From a public health
      perspective, it is assumed that the interest of this proposal is to reduce the
      problematic use of cannabis, to effectively fight against illicit drug
      trafficking and drug-related crime, as well as health promotion and prevention of
      addictions and other adverse health impacts. This article reveals that the
      effects of legalization might, contrary to general beliefs, generate positive
      results with respect to these aims, given that there will be greater control on
      the market, price, quality, and information - to name a few - if implementation
      occurs with proper consideration and definition. CONCLUSION: The debate on the
      responsible and safe legalization of cannabis use in Portugal should be open and
      promoted, based on a public health perspective.

PMID- 29596772
TI  - [Tick Infestation of the Eyelid: Case Report and Literature Review].
AB  - Tick infestation is rarely seen in ophthalmological practice. We report the case
      of a 73-year-old woman who presented with edema and erythema of her right upper
      eyelid. Biomicroscopic examination revealed a tick firmly attached to the eyelid
      margin. The tick was successfully removed using fine tweezers, and within a few
      days, the patient had fully recovered without sequelae. Ticks are a threat to
      public health as they are known vectors of numerous infectious agents responsible
      for serious pathologies such as Lyme disease. Ticks may also induce cutaneous
      local reactions, and more rarely, tick paralysis. Since morbidity increases
      substantially with the duration of the infestation, the tick should be completely
      removed as soon as possible, and patients should be aware about possible signs of
      tick related diseases.

PMID- 29596773
TI  - [Fulminant Emphysematous Pyelonephritis Secondary to Urothelial Neoplasia with
      Reno-Colic Fistula].
AB  - The emphysematous pyelonephritis is a uncommon and potentially fatal entity. The
      recognition of this condition enables the early correct management of patients.
      Diabetes and ureteral obstruction are the main risk factors identified. We
      present the case of a patient with no relevant risk factors or prior medical
      history, in which the reason of admission to the emergency department was back
      pain, eventually evolving into septic shock in the early hours. The imaging tests
      identified the presence of peri-renal and subcutaneous gas which guided the
      medical team to the right diagnosis (emphysematous pyelonephritis secondary to
      fistulized urothelial neoplasia) and the optimal surgical treatment. However, in
      the post-operative period the patient died, as the clinical condition and
      laboratory test results performed during the admission were predicting. It should
      also be mentioned that this same case illustrated a bacteraemia by Sphingomonas
      Paucimobilis (acquired in the community) with cavitated damage to lungs (probable
      septic embolism).

PMID- 29596774
TI  - Mucosal and Periungual Telangiectasia as Signs of Systemic Disease.

PMID- 29596775
TI  - [Letter to the Editor: Anaphylaxis, Diagnosis and Treatment].

PMID- 29596776
TI  - [Reply to the Letter to the Editor: Still About Delirium].

PMID- 29596777
TI  - Pillars for a New Era of Cancer Research.

PMID- 29596778
TI  - Principles of Systems Biology, No. 27.
AB  - This month: protein-complex dynamics (Tan), how noise promotes cell survival
      (Goulian), multiplex cell-surface-protein detection (Wells), single-cell
      sequencing (Klein/Socolovsky, Ye), social networks of honeybees (Robinson), new
      synthetic devices (Liu, Cai), and controlling segmentation clock dynamics
      (Aulehla).

PMID- 29596779
TI  - What Fundamental Questions in Cancer Would Most Benefit from Math, Engineering,
      and AI?

PMID- 29596781
TI  - Friends with Benefits: Microenvironmental NRG1beta and HGF Mediate HER2-Targeted
      Resistance in L-HER2+ and HER2E Breast Cancer.
AB  - Watson et al. use microenvironment microarrays to assess how extrinsic signals
      within the tumor microenvironment influence HER2++ breast cancer resistance to
      the HER2-targeted tyrosine kinase inhibitor lapatinib.

PMID- 29596780
TI  - Escaping Circadian Regulation: An Emerging Hallmark of Cancer?
AB  - Alterations of circadian clock genes are associated with patient survival, tumor
      stage, and clinical subtype across various cancer types, highlighting the
      importance of timing in cancer treatment.

PMID- 29596785
TI  - Pulmonary Tumor Microembolism: When the Pathologist Looks Further Than the
      Radiologist.

PMID- 29596784
TI  - Contraceptive use by disability status: new national estimates from the National
      Survey of Family Growth.
AB  - OBJECTIVE: The objective was to determine population-based estimates of use of
      contraception among women 15-44 years of age in the United States by disability
      status. STUDY DESIGN: We examined the relationship between disability status and
      use of contraception among 7505 women at risk of unintended pregnancy using data
      from the 2011-2015 National Survey of Family Growth. RESULTS: After examining the
      full distribution of contraceptive method use by disability status, we found that
      disability status was significantly associated with differences in three
      categories of use: female sterilization, the oral contraceptive pill and nonuse
      of contraception. Multivariate analysis shows that use of female sterilization
      was higher among women with cognitive disabilities (aOR=1.54, 95% CI=1.12-2.12)
      and physical disabilities (aOR=1.59, CI=1.08-2.35) than for those without
      disabilities after controlling for age, parity, race, insurance coverage and
      experience of unintended births. Use of the pill was less common among women with
      physical disabilities than for those without disabilities (aOR=0.57, CI=0.40
      0.82). Finally, not using a method was more common among women with cognitive
      disabilities (aOR=1.90, CI=1.36-2.66). CONCLUSIONS: Self-reported cognitive
      disabilities ("serious difficulty concentrating, remembering or making
      decisions"), as well as physical disabilities, are significant predictors of
      contraceptive choices after controlling for several known predictors of use.
      IMPLICATIONS: The patterns found here suggest that screening for self-reported
      cognitive and physical disabilities may allow health care providers to tailor
      counseling and sex education to help women with disabilities prevent unintended
      pregnancy and reach their family size goals.

PMID- 29596786
TI  - From Mechanical to Chemical: A Case of Diabetes Insipidus Induced by Concussive
      Brain Injury.

PMID- 29596787
TI  - Gradually Transformed: Parry-Romberg Syndrome.

PMID- 29596788
TI  - Diabetes Mellitus and Cardiogenic Shock Complicating Acute Myocardial Infarction.
AB  - BACKGROUND: Diabetes mellitus (diabetes) increases the risk of acute myocardial
      infarction, which can result in cardiogenic shock. Data on the relation of
      diabetes and the occurrence and prognosis of cardiogenic shock postacute
      myocardial infarction are scant. METHODS: Among the National Inpatient Sample
      patients aged >=18 years and hospitalized for acute myocardial infarction during
      the 2012-2014 period, we examined the association between diabetes and the
      incidence and outcomes of cardiogenic shock complicating acute myocardial
      infarction, using multivariable logistic and linear regression models. RESULTS:
      Of 1,332,530 hospitalizations for acute myocardial infarction, 72,765 (5.5%) were
      complicated by cardiogenic shock. In acute myocardial infarction patients,
      cardiogenic shock incidence was higher among those with vs without diabetes (5.8%
      vs 5.2%; adjusted odds ratio [aOR] 1.14; 95% confidence interval [CI], 1.11-1.19;
      P < .001), with 42.8% (n = 31,135) of patients with acute myocardial infarction
      and cardiogenic shock having diabetes. Diabetic patients were less likely to
      undergo revascularization (percutaneous coronary intervention or coronary artery
      bypass grafting) (67.1% vs 68.7%; aOR 0.88; 95% CI, 0.80-0.96; P = .003).
      Diabetes was associated with higher in-hospital mortality in patients with acute
      myocardial infarction and cardiogenic shock (37.9% vs 36.8%; aOR 1.18; 95% CI,
      1.09-1.28; P < .001). Among survivors, patients with diabetes had a longer
      hospital stay (mean +/- SEM: 11.6 +/- 0.16 vs 10.9 +/- 0.16 days; adjusted
      estimate 1.12; 95% CI, 1.06-1.18; P < .001) and were more likely to be discharged
      to a skilled nursing home or with home health care (56.0% vs 50.5%; aOR 1.19; 95%
      CI, 1.07-1.33; P = .001). CONCLUSIONS: In a large cohort of acute myocardial
      infarction patients, preexisting diabetes was associated with an increased risk
      of cardiogenic shock and worse outcomes in those with cardiogenic shock.

PMID- 29596789
TI  - Electron sweep across four b-hemes of cytochrome bc1 revealed by unusual
      paramagnetic properties of the Qi semiquinone intermediate.
AB  - Dimeric cytochromes bc are central components of photosynthetic and respiratory
      electron transport chains. In their catalytic core, four hemes b connect four
      quinone (Q) binding sites. Two of these sites, Qi sites, reduce quinone to quinol
      (QH2) in a step-wise reaction, involving a stable semiquinone intermediate (SQi).
      However, the interaction of the SQi with the adjacent hemes remains largely
      unexplored. Here, by revealing the existence of two populations of SQi differing
      in paramagnetic relaxation, we present a new mechanistic insight into this
      interaction. Benefiting from a clear separation of these SQi species in mutants
      with a changed redox midpoint potential of hemes b, we identified that the fast
      relaxing SQi (SQiF) corresponds to the form magnetically coupled with the
      oxidized heme bH (the heme b adjacent to the Qi site), while the slow-relaxing
      SQi (SQiS) reflects the form present alongside the reduced (and diamagnetic) heme
      bH. This so far unreported SQiF calls for a reinvestigation of the thermodynamic
      properties of SQi and the Qi site. The existence of SQiF in the native enzyme
      reveals a possibility of an extended electron equilibration within the dimer,
      involving all four hemes b and both Qi sites. This substantiates the predicted
      earlier electron transfer acting to sweep the b-chain of reduced hemes b to
      diminish generation of reactive oxygen species by cytochrome bc1. In analogy to
      the Qi site, we anticipate that the quinone binding sites in other enzymes may
      contain yet undetected semiquinones which interact magnetically with oxidized
      hemes upon progress of catalytic reactions.

PMID- 29596790
TI  - Morphological and molecular characterization of Paragonimus caliensis Little,
      1968 (Trematoda: Paragonimidae) from Medellin and Pichinde, Colombia.
AB  - Paragonimiasis is a subacute to chronic inflammatory granulomatous lung disease
      caused by the genus Paragonimus. In Latin America Paragonimus mexicanus Miyazaki
      & Ishii, 1968 is the only confirmed species to cause human infections.
      Paragonimus caliensis Little, 1968 is an uncommon species often regarded as a
      synonym of P. mexicanus. Recently, the study of two types of Paragonimus
      metacercariae from Costa Rica has provided new molecular and morphological
      evidence that P. caliensis is a separate species from P. mexicanus. In the
      present study, molecular, morphological and phylogenetic tools have been used to
      characterize two populations of Paragonimus located at west of Medellin,
      Antioquia and at Pichinde, Valle del Cauca (type locality of P. caliensis),
      Colombia. Adults and metacercariae obtained from Medellin, and metacercariae from
      Pichinde were analyzed. For morphological observations we used light microscopy
      and scanning electron microscopy (SEM). Morphology of metacercariae and adults
      matched with the holotype of P. caliensis. The number and arrangement of sensory
      papillae in the acetabulum region differs from the morphotypes reported for P.
      caliensis in Costa Rica. Two morphotypes in branching patterns of ovary and two
      morphotypes in branching patterns of testes were identified. The main
      morphological differences between P. caliensis and P. mexicanus corresponded to
      the size of gonads and their relative positions in the body, and the occasional
      presence of a cyst wall in P. caliensis metacercariae. The molecular and
      phylogenetic analyses (using nuclear ribosomal ITS2 and partial cytochrome c
      oxidase subunit 1 CO1 sequences) confirmed that P. caliensis from the type
      locality is the same species from Medellin and Costa Rica. Furthermore, these
      analyses also suggest genetic as well as geographical separation of P. caliensis
      populations between Colombia and Costa Rica. Currently, P. mexicanus and P.
      caliensis are sympatric in the Colombian Pacific bioregion, and specific
      diagnosis based on their egg size is not possible. Therefore, it is necessary to
      determine the biogeographic distribution ranges of both species and to implement
      molecular techniques to establish the role of P. caliensis in human
      paragonimiasis in Colombia.

PMID- 29596792
TI  - First two-reagent vitamin D assay for general clinical chemistry.
AB  - BACKGROUND: Vitamin D is a lipid-soluble molecule that plays key physiological
      roles in the metabolism of calcium, phosphate and magnesium. Recent studies show
      that deficiency in vitamin D is linked to cardiovascular diseases, autoimmune
      diseases and cancer. As a result, regular monitoring of 25-OH vitamin D (the main
      circulating form of vitamin D) is becoming essential. Current 25-OH vitamin D
      testing methodologies are cumbersome (too many reagents, long incubation times,
      phase separation) and are not compatible with general clinical chemistry
      platforms. Here, we report on a novel method to detect 25-OH vitamin D that is
      fast (results in 10 min or less), simple (two reagents) and compatible with
      virtually all general clinical chemistry analyzers. METHODS: An
      immunoturbidimetric assay for 25-OH vitamin D (the Diazyme EZ Vitamin D Assay)
      has been developed using nanoparticles and vitamin D-specific antibodies. The
      performance of the assay kit, which consists of two reagents and five
      calibrators, was tested on the Beckman AU680 analyzer (AU680). RESULTS: The new
      assay was precise, sensitive (LOD = 7.2 nmol/L), linear (up to 390.1 nmol/L) and
      correlated strongly (R2 > 0.95) with major commercial 25-OH vitamin D assays.
      Additionally, the assay was found to be the fastest to date, with the first
      results obtained within 10 min. Throughput on the AU680 was estimated at over 300
      tests per hour. CONCLUSIONS: The newly developed 25-OH vitamin D assay is fast,
      precise and accurate. It can be run on most general chemistry analyzers. This
      assay aims at providing vitamin D-testing capabilities to all clinical chemistry
      laboratories.

PMID- 29596794
TI  - Selection of Submucosal Steroids to Minimize Postsurgical Pain.

PMID- 29596791
TI  - Optimization and 13CH3 methionine labeling of a signaling competent neurotensin
      receptor 1 variant for NMR studies.
AB  - Neurotensin is a 13-residue peptide that acts as a neuromodulator of classical
      neurotransmitters such as dopamine and glutamate in the mammalian central nervous
      system, mainly by activating the G protein-coupled receptor (GPCR), neurotensin
      receptor 1 (NTS1). Agonist binding to GPCRs shifts the conformational equilibrium
      of the transmembrane helices towards distinct, thermodynamically favorable
      conformations that favor effector protein interactions and promotes cell
      signaling. The introduction of site specific labels for NMR spectroscopy has
      proven useful for investigating this dynamic process, but the low expression
      levels and poor stability of GPCRs is a hindrance to solution NMR experiments.
      Several thermostabilized mutants of NTS1 have been engineered to circumvent this,
      with the crystal structures of four of these published. The conformational
      dynamics of NTS1 however, has not been thoroughly investigated with NMR. It is
      generally accepted that stabilized GPCRs exhibit attenuated signaling, thus we
      thoroughly characterized the signaling characteristics of several
      thermostabilized NTS1 variants to identify an optimal variant for protein NMR
      studies. A variant termed enNTS1 exhibited the best combination of signaling
      capability and stability upon solubilization with detergents. enNTS1 was
      subsequently labeled with 13CH3-methionine in E. coli and purified to homogeneity
      in the absence of bound ligands. Using solution NMR spectroscopy we observed
      several well dispersed 13CH3-methionine resonances, many of which exhibited
      chemical shift changes upon the addition of the high affinity agonist peptide,
      NT8-13. Thus, enNTS1 represents a novel tool for investigating ligand induced
      conformational changes in NTS1 to gain insights into the molecular mechanisms
      underlying neurotensin signaling.

PMID- 29596793
TI  - Correlation of oxidative stress in patients with HBV-induced liver disease with
      HBV genotypes and drug resistance mutations.
AB  - OBJECTIVE: This study aims to explore the correlation of oxidative stress (OxS)
      in patients with chronic hepatitis B (CHB) and the disease severity with HBV
      genotypes and drug resistance mutations. METHODS: A total of 296 patients with
      CHB were enrolled into the study. PCR-reverse dot-blot hybridization was used to
      detect the HBV genotypes (B, C, and D) and the drug resistance-causing HBV mutant
      genes. In addition, the total oxidative stress (TOS) and total antioxidant status
      (TAS) were determined, and oxidative stress index (OSI) was calculated and
      compared. RESULTS: Serum levels of TOS and OSI, the B/C ratio, and drug
      resistance mutation rate were increased along with the elevated disease severity
      degree (CHB<HBC<HCC) (P < 0.05), while the serum TAS level showed the opposite
      trend (though there was no statistical difference between patients at the CHB and
      HBC stages). Moreover, patients with drug resistance-causing HBV mutation had
      higher serum TOS and OSI levels, while lower serum TAS levels (P < 0.05),
      compared with patients without mutations. Furthermore, mutation site numbers were
      positively correlated with the disease severity degree (gamma = 0.614, P <
      0.001). CONCLUSION: There is oxidative damage in patients with HBV-induced liver
      disease, and the damage degree is correlated with the HBV genotype and drug
      resistance mutation. Oxidative stress might be a useful indicator of the
      progression of HBV-induced liver disease in patients.

PMID- 29596795
TI  - In reply.

PMID- 29596796
TI  - Obstructive Sleep Apnea: An Ill Eye in the Wind.

PMID- 29596797
TI  - Biological and pharmacological effects of hexahydrocurcumin, a metabolite of
      curcumin.
AB  - Curcumin, one of the most precious pharmacologically relevant natural products,
      has gained considerable attention among scientists for decades because of its
      multi-pharmacological activities in the clinical. However, critical studies on
      its pharmacological and toxicological activities are needed to understand how
      this compound can have these biological functions considering its poor oral
      bioavailability and the low plasma concentration. Moreover, curcumin undergoes
      extensive and rapid metabolism in vivo, indicating that the pharmacological
      activity of consuming curcumin might be mediated partly by its metabolites. And
      as one of the major curcumin metabolites, hexahydrocurcumin (HHC), exhibits
      similar or more potent bioactivity than curcumin by in vitro and in vivo studies,
      such as antioxidant, anti-inflammatory, antitumor and cardiovascular protective
      properties, which may provide important information for us to have a profound
      comprehension of the effectiveness of curcumin. This review mainly summarizes the
      current knowledge and underlying molecular mechanisms of the biological
      activities of HHC and its potential effects on the development of various human
      diseases.

PMID- 29596798
TI  - Neuroprotective effect of paeoniflorin on okadaic acid-induced tau
      hyperphosphorylation via calpain/Akt/GSK-3beta pathway in SH-SY5Y cells.
AB  - Abnormal phosphorylation of tau, one of the most common symptoms of dementia, has
      become increasingly important in the study of the etiology and development of
      Alzheimer's disease. Paeoniflorin, the main bioactive component of herbaceous
      peony, is a monoterpene glycoside, which has been reported to exert beneficial
      effects on neurodegenerative disease. However, the effect of paeoniflorin on
      tauopathies remains ambiguous. SH-SY5Y cells were treated with okadaic acid (OA)
      for 8 h to induce tau phosphorylation and no cell death was observed. Optical
      microscopy results showed that paeoniflorin ameliorated okadaic acid induced
      morphological changes, including cell swelling and synapsis shortening. Western
      blotting data illustrated that paeoniflorin reversed okadaic acid induced tau
      hyperphosphorylation, which was enhanced by inhibiting the activities of calpain,
      Akt and GSK-3beta. Transmission electron microscopy results showed that
      paeoniflorin alone can reduce the number of autophagosomes and stabilize the
      microtubule structure. In addition, calpastain and paeoniflorin enhance the
      effect of paeoniflorin on stabilizing microtubules. In addition, calpastain
      markedly enhanced the effect of paeoniflorin on reversing okadaic acid-lowered
      fluorescence intensity of both MAP-2 and beta III-tubulin, two microtubule
      associated proteins. This study shows that paeoniflorin protected SH-SY5Y cells
      against okadaic acid assault by interfering with the calpain/Akt/GSK-3beta
      related pathways, in which autophagy might be involved. Besides, paeoniflorin is
      found to relieve the stress response of the microtubule structure system caused
      by okadaic acid treatment. The results presented in this study suggest that
      paeoniflorin potentially plays an important role in tauopathies.

PMID- 29596800
TI  - Molecular interactions of active constituents of essential oils in zwitterionic
      lipid bilayers.
AB  - Eugenol and its related compounds are major active constituents of essential oils
      and have been extensively used as food flavoring agents with significant lipid
      peroxidation inhibition activity, highlighting the importance of understanding
      detailed molecular mechanisms behind their interactions with lipid bilayer. For
      this, we studied antioxidant activity of essential oils rich extract of
      Cinnamomum tamala leaves and molecular dynamics simulations of eugenol,
      isoeugenol, methyleugenol, acetyleugenol and eugenol oxide in POPC and PLPC lipid
      bilayers. All the compounds penetrated into bilayer however, isoeugenol showed
      highest affinity for the pure POPC and PLPC bilayers with lowest free energy
      profiles, formed more H-bonds with bilayer oxygen atoms and more pronounced
      changes in area per lipid and thickness of the bilayer, thus more efficient for
      scavenging radicals coming from outside as well as centrally located lipid
      peroxyl radicals. These molecular interactions rationalize the difference in
      inhibition activities of lipid peroxidation by eugenol and its related compounds.

PMID- 29596799
TI  - p53 mediated transcriptional regulation of long non-coding RNA by 1-hydroxy-1
      norresistomycin triggers intrinsic apoptosis in adenocarcinoma lung cancer.
AB  - Over a few decades, systemic chemotherapy and surgery are the only treatment
      options for lung cancer. Due to limited efficacy and overall poor survival of
      patients, it is necessary to develop a newer therapeutic strategy which
      specifically targets cancer cell proliferation pathway. Deciphering the role of
      long non-coding RNAs (lncRNAs) in tumorigenesis and pathogenesis of cancer cells
      has recently emerged. In the present study, marine actinomycetes derived 1
      hydroxy-1-norresistomycin (HNM) was used to enhance the expression of lncRNAs
      through p53 transcriptional regulation and induced intrinsic apoptosis in non
      small cell lung cancer cells. Initially, concentration dependent treatment with
      HNM has increased the ROS generation in mitochondria and sensitizes the
      mitochondrial membrane potential. Further, HNM downregulates the numerous
      oncogenes which regulate cancer cell proliferation, metastasis and invasion and
      tumor suppressor genes which are involved in intrinsic apoptosis confirmed with
      adopting techniques such as RT-PCR and western blot analysis. Moreover, ChIP
      assay results showed that HNM upregulates the p53 mediated transcriptional
      regulation of lncRNAs lead to apoptosis of cancer cells through cell cycle arrest
      and inhibition of proliferation. In conclusion, HNM found to be a potential
      therapeutic agent for treatment of lung cancer via suppression of oncogenes and
      expression of wide range of tumor suppressor genes are might have significant
      implications in cancer treatment and drug development.

PMID- 29596801
TI  - Corrigendum to 'Self-tolerance and autoimmunity in a minimal model of the
      idiotypic network' [Journal of Theoretical Biology 426 (2017) 17-39].

PMID- 29596802
TI  - Re: Trends in Prostate Cancer Incidence Rates and Prevalence of Prostate Specific
      Antigen Screening by Socioeconomic Status and Regions in the United States, 2004
      to 2013: K. A. Houston, J. King, J. Li and A. Jemal J Urol 2018;199:676-682.

PMID- 29596803
TI  - Reply by Authors.

PMID- 29596804
TI  - Re: Risk Stratification of Equivocal Lesions on Multiparametric Magnetic
      Resonance Imaging of the Prostate: T. Ullrich, M. Quentin, C. Arsov, A. K.
      Schmaltz, A. Tschischka, N. Laqua, A. Hiester, D. Blondin, R. Rabenalt, P.
      Albers, G. Antoch and L. Schimmoller J Urol 2018;199:691-698.

PMID- 29596805
TI  - Reply by Authors.

PMID- 29596806
TI  - Re: Missed Opportunities to Decrease Radiation Exposure in Children with Renal
      Trauma: T. W. Gaither, M. A. Awad, N. V. Leva, G. P. Murphy, B. N. Breyer and H.
      L. Copp J Urol 2018;199:552-557.

PMID- 29596808
TI  - Reply by Authors.

PMID- 29596807
TI  - Editorial Comment.

PMID- 29596809
TI  - Editorial Comment.

PMID- 29596810
TI  - Editorial Comment.

PMID- 29596811
TI  - Reply by Authors.

PMID- 29596812
TI  - Application of nanomaterials for the electrical and optical detection of the
      hepatitis B virus.
AB  - This work describes different approaches for the detection of hepatitis B virus
      (HBV) genomic DNA, using electrochemical and optical techniques. The platforms
      consisted of a single-stranded DNA probe (HEPB1S), specific to HBV, grafted on a
      gold electrode modified with reduced graphene oxide or gold nanoparticles.
      Differential pulse voltammetry analysis indicates that the addition of HBV
      genomic DNA caused an increase of about 1.4 times in the current peak value, when
      compared to the negative control. It was observed a linear dependence with the
      log HBV-genomic DNA concentration and the electrochemical biosensor detected
      until 7.65 pg MUL-1 of the target. Electrochemical impedance spectroscopy
      measurements showed an increase of about 2 times in the charge transfer
      resistance, after the addition of HBV genomic DNA. Assays using colloidal
      suspension of gold nanoparticles showed a shift of the peak wavelength, linearly
      proportional to the HBV-genomic DNA concentration, with a detection limit of 0.15
      ng MUL-1. The applicability of the gold nanoparticles for clinical samples was
      tested with success in the blood plasma. All the approaches used in this work
      were effective in detecting genomic DNA or blood plasma in positive samples for
      HBV.

PMID- 29596813
TI  - Circulating parathyroid hormone and risk of hypertension: A meta-analysis.
AB  - OBJECTIVES: To examine the relationship between circulating parathyroid hormone
      (PTH) level and risk of hypertension (HTN). METHODS: The electronic databases of
      PubMed, Web of Science and Embase were searched up to December 2017, for
      prospective cohort studies on the relationship between circulating PTH level and
      risk of HTN. The pooled relative risk (RR) of HTN for the highest versus lowest
      category of circulating PTH level as well as their corresponding 95% confidence
      interval (CI) were calculated. RESULTS: A total of six prospective cohort
      studies, which involved 18,994 participants and 5040 HTN cases, were included in
      this meta-analysis. The overall multi-variable adjusted RR showed a positive
      relationship between circulating PTH level and risk of HTN (RR = 1.35, 95%CI:
      1.09 to 1.67; P = 0.006). A substantial level of heterogeneity was observed among
      the studies (P < 0.001, I2 = 77.6%). No evidence of publication bias was observed
      among the studies according to Begg's rank-correlation test (P = 0.452).
      CONCLUSIONS: The existing evidence suggests that an increase in circulating PTH
      level may be associated with a higher risk of HTN. However, due to the limited
      number of included studies, more well-designed prospective cohort studies are
      needed to further elaborate the issues examined in this study.

PMID- 29596814
TI  - Lactase persistence genotyping on whole blood by loop-mediated isothermal
      amplification and melting curve analysis.
AB  - BACKGROUND: The lactase persistence phenotype is controlled by a regulatory
      enhancer region upstream of the Lactase (LCT) gene. In northern Europe,
      specifically the -13910C > T variant has been associated with lactase persistence
      whereas other persistence variants, e.g. -13907C > G and -13915 T > G, have been
      identified in Africa and the Middle East. The aim of the present study was to
      compare a previously developed high resolution melting assay (HRM) with a novel
      method based on loop-mediated isothermal amplification and melting curve analysis
      (LAMP-MC) with both whole blood and DNA as input material. METHODS: To evaluate
      the LAMP-MC method, we used 100 whole blood samples and 93 DNA samples in a two
      tiered study. First, we studied the ability of the LAMP-MC method to produce
      specific melting curves for several variants of the LCT enhancer region. Next, we
      performed a blinded comparison between the LAMP-MC method and our existing HRM
      method with clinical samples of unknown genotype. RESULTS: The LAMP-MC method
      produced specific melting curves for the variants at position -13909, -13910, 
      13913 whereas the -13907C > G and -13915 T > G variants produced
      indistinguishable melting profiles. CONCLUSION: The LAMP-MC assay is a simple
      method for lactase persistence genotyping and compares well with our existing HRM
      method.

PMID- 29596782
TI  - Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using
      Multiple Genomic Pipelines.
AB  - The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor
      normal exome pairs across 33 different cancer types, in total >400 TB of raw data
      files requiring analysis. Here we describe the Multi-Center Mutation Calling in
      Multiple Cancers project, our effort to generate a comprehensive encyclopedia of
      somatic mutation calls for the TCGA data to enable robust cross-tumor-type
      analyses. Our approach accounts for variance and batch effects introduced by the
      rapid advancement of DNA extraction, hybridization-capture, sequencing, and
      analysis methods over time. We present best practices for applying an ensemble of
      seven mutation-calling algorithms with scoring and artifact filtering. The
      dataset created by this analysis includes 3.5 million somatic variants and forms
      the basis for PanCan Atlas papers. The results have been made available to the
      research community along with the methods used to generate them. This project is
      the result of collaboration from a number of institutes and demonstrates how team
      science drives extremely large genomics projects.

PMID- 29596816
TI  - Comparison of serum serotonin and serum 5-HIAA LC-MS/MS assays in the diagnosis
      of serotonin producing neuroendocrine neoplasms: A pilot study.
AB  - BACKGROUND: Serotonin (5-hydroxytyramine) is a mediator of gastrointestinal
      smooth muscle contraction, and is secreted by neuroendocrine neoplasms (NENs). We
      developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for
      serum serotonin to be used in NEN diagnostics and follow-up. METHODS: We used
      serum samples from healthy volunteers (n = 31) and patients suspected or
      monitored for NEN (n = 98). Serotonin-D4 internal standard was added to samples
      before solid phase extraction (SPE) and quantification by LC-MS/MS. The effects
      of sample handling and preparation on serotonin stability were studied. Finally,
      we established a provisional reference range for serum serotonin and compared our
      assay with serum 5-hydroxyindoleacetic acid (5-HIAA) for detection of NENs.
      RESULTS: Our assay is sensitive and has a wide linear range (10-10,000 nmol/l).
      Serum serotonin is stable for 7 days at room temperature and for 3 months at -20 
      degrees C. Sampling temperature is not critical. Normal range for serum serotonin
      was 270-1490 nmol/l. We found that serum serotonin and 5-HIAA performed equally
      well as diagnostic tests for NENs. CONCLUSIONS: Our LC-MS/MS assay for serum
      serotonin is well suited for clinical research and patient diagnostics. Our
      results confirm that it can complement 5-HIAA in diagnosis of NENs.

PMID- 29596817
TI  - Isolated Hemorrhagic Pericardial Effusion After Foreign Body Ingestion.
AB  - Foreign body ingestion is one of the many potential causes of esophageal
      perforation. In this case report we describe a man who presented with chest pain
      and was found to have an isolated hemorrhagic pericardial effusion secondary to
      occult ingestion and pericardial migration of a metallic foreign body. Surgical
      management was successful, and the patient has recovered well.

PMID- 29596815
TI  - Therapeutic drug monitoring of piperacillin and tazobactam by RP-HPLC of residual
      blood specimens.
AB  - BACKGROUND: Sepsis is a common diagnosis in critical care with inpatient
      mortality rates up to 50%. Sepsis care is organized around source control,
      antibiotics, and supportive care. Drug disposition is deranged by changes in
      volume of distribution and regional blood flow, as well as multiple organ
      failure. Thus, assuring that each patient with sepsis attains pharmacokinetic
      targets is challenging. There is currently no commercially available FDA-approved
      assay to measure piperacillin-tazobactam, very commonly used as a beta
      lactam/beta-lactamase inhibitor combination antibiotic in the intensive care unit
      (ICU). METHODS: Samples were prepared by ultrafiltration of plasma collected in
      lithium heparin Vacutainers. Separation was achieved by gradient elution on a C
      18 column followed by UV detection at 214 nm. The method is validated in residual
      blood samples allowing investigators to exploit a waste product to develop
      insight into beta-lactam pharmacokinetics in the ICU. RESULTS: Accuracy and
      precision were within the 25% CLIA error standard for other antibiotic assays.
      Free piperacillin concentrations were also in good agreement with total
      piperacillin concentrations measured in the same plasma by an assay in clinical
      use outside the United States. CONCLUSION: We describe a method for measuring
      piperacillin and tazobactam that meets clinical validation standards. Quick
      turnaround time and excellent accuracy on a low-cost platform make this method
      more than adequate for use as a routine therapeutic drug monitoring tool.

PMID- 29596818
TI  - Clinical Outcomes of Root Reimplantation and Bentall Procedure: Propensity Score
      Matching Analysis.
AB  - BACKGROUND: This study aimed to evaluate the clinical outcomes of aortic root
      replacement (ARR) surgery: Root reimplantation as valve-sparing root replacement
      (VSR) and the Bentall procedure. METHODS: We retrospectively reviewed 216
      patients who underwent ARR between 1995 and 2013 at Samsung Medical Center.
      Patients were divided into two groups, depending on the procedure they underwent:
      Bentall (n = 134) or VSR (n = 82). The mean follow-up duration was 100.9 +/- 56.4
      months. RESULTS: There were 2 early deaths in the Bentall group and none in the
      VSR group (p = 0.53). Early morbidities were not different between the groups.
      Overall mortality was significantly lower in the VSR group (HR = 0.12, p = 0.04).
      Despite the higher reoperation rate in the VSR group (p = 0.03), major adverse
      valve-related events (MAVRE) did not differ between the groups (p = 0.28).
      Bleeding events were significantly higher in the Bentall group during follow-up
      (10 in Bentall group, 0 in VSR group, p = 0.04). There were 6 thromboembolic
      events only in the Bentall group (p = 0.11). We performed a propensity score
      matching analysis comparing the groups (134 Bentall versus 43 VSR). Matched
      analysis gave similar results, namely, HR = 0.17, p = 0.10 for overall mortality
      and HR = 1.01, p = 0.99 for MAVRE. CONCLUSIONS: Although there was marginal
      significance in the propensity matched analysis, it is plausible to anticipate a
      survival benefit with VSR during long-term follow-up. Despite a higher
      reoperation for aortic valves, VSR can be a viable option in patients who decline
      life-long anticoagulation, especially the young or the patients in whom
      anticoagulation is contraindicated.

PMID- 29596820
TI  - Patterns of Practice in Mediastinal Lymph Node Staging for Non-Small Cell Lung
      Cancer in Canada.
AB  - BACKGROUND: Assessment of mediastinal lymph nodes is integral in staging patients
      with non-small cell lung cancer (NSCLC). This study delineated the lymph node
      staging practices of Canadian thoracic surgeons in patients with potentially
      resectable NSCLC. METHODS: A questionnaire was distributed to Canadian
      Association of Thoracic Surgeons members (n = 86). Items addressed the use of
      imaging, thresholds/methods for preoperative invasive staging, and intraoperative
      node staging. Comparison was made against Canadian, American, and European
      guidelines. RESULTS: Forty-seven surgeons (55%) responded. Although most stated
      they derived practices from published guidelines, a significant proportion did
      not reflect those recommendations. Most respondents ordered a positron emission
      tomography scan for every patient (87.2%), and the same proportion (87.2%)
      performed invasive staging selectively, with a wide range of indications. The
      most common thresholds were suspicious nodes on imaging (80.5%), tumor within the
      central third of the lung (67.5%), and tumor exceeding 3 cm (34.2%).
      Endobronchial ultrasound, alone or with endoscopic ultrasound, was selected as
      the initial staging procedure of choice by 47.9%, and 43.5% selected
      mediastinoscopy first. Of surgeons selecting mediastinoscopy, 61.9% reported some
      barriers to performing endobronchial ultrasound. There was variability, between
      surgeons and between lobes, in which nodes respondents harvested intraoperatively
      for given lobectomies. A sizeable minority (13%) did not routinely harvest lymph
      nodes intraoperatively. CONCLUSIONS: Determining the appropriate treatment and
      prognosis of NSCLC patients relies on proper staging. Significant variability
      exists in node staging practices in Canada as well as divergence from guidelines.
      This may result in understaging or overstaging patients and inappropriate care.

PMID- 29596819
TI  - Dehiscence of Bronchial Anastomosis After Lung Transplantation: A Successful
      Unconventional Treatment.
AB  - Anastomotic airway complications, including the dehiscence of the bronchial
      anastomosis, are a severe cause of morbidity after lung transplantation. We
      present a case of dehiscence treated by placing an uncovered metal stent into the
      main bronchus. We usually use this procedure for bronchial stenosis, but in this
      case, the stent favored the growth of granulation tissue and so the closure of
      the dehiscence. This procedure was minimally invasive and may be an alternative
      to an open repair, without precluding open repair in case of failure.

PMID- 29596783
TI  - Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the
      Cancer Genome Atlas.
AB  - Although the MYC oncogene has been implicated in cancer, a systematic assessment
      of alterations of MYC, related transcription factors, and co-regulatory proteins,
      forming the proximal MYC network (PMN), across human cancers is lacking. Using
      computational approaches, we define genomic and proteomic features associated
      with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan
      cancer, 28% of all samples had at least one of the MYC paralogs amplified. In
      contrast, the MYC antagonists MGA and MNT were the most frequently mutated or
      deleted members, proposing a role as tumor suppressors. MYC alterations were
      mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that
      MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated
      pathways in tumor subtypes, such as immune response and growth factor signaling;
      chromatin, translation, and DNA replication/repair were conserved pan-cancer.
      This analysis reveals insights into MYC biology and is a reference for biomarkers
      and therapeutics for cancers with alterations of MYC or the PMN.

PMID- 29596821
TI  - Intraoperative Device Closure of Isolated Ventricular Septal Defects: Experience
      on 1,090 Cases.
AB  - BACKGROUND: This study summarizes the clinical experience and 8-year follow-up
      results of the intraoperative device closure of ventricular septal defects (VSD).
      METHODS: From January 2009 to June 2017, 1,090 patients with isolated VSD were
      enrolled at our institute to participate in the study. The procedure involved a
      small lower sternal incision that was performed after full evaluation of VSD by
      transesophageal/transthoracic echocardiographic (TEE/TTE) guidance and the
      deployment of a domestically made occluder to close the VSD periventricularly and
      off cardiopulmonary bypass. Follow-up was in the first 3 months and then every 1
      to 2 years with TTE, electrocardiography, and upon symptoms. RESULTS: In all,
      1,033 patients were occluded successfully under this approach, and the remaining
      patients were converted to surgical repair. The size of the occluder deployed
      ranged from 6 to 14 mm and included 825 symmetric devices and 208 asymmetric
      devices. A total of 25 patients developed severe arrhythmias, including 11 cases
      of complete atrioventricular block and 14 cases of Mobitz type II
      atrioventricular block, during and after the procedure. CONCLUSIONS: Minimally
      invasive transthoracic device closure of VSD with an asymmetric or symmetric
      domestically made device on a beating heart is a safe and feasible alternative to
      conventional surgical repair. More experience in multicenter and long-term follow
      up is necessary to assess the actual feasibility and safety of this procedure.

PMID- 29596822
TI  - Impact of Regional Collaboration on Quality Improvement and Associated Cost
      Savings in Coronary Artery Bypass Grafting.
AB  - BACKGROUND: A statewide database identified prolonged ventilation (PV) and acute
      renal failure (RF) as the biggest cost drivers after isolated coronary artery
      bypass grafting. Reducing these complications through regional collaboration
      should improve outcomes and lower health care costs. METHODS: A total of 27,978
      patients who underwent isolated coronary artery bypass grafting were divided into
      pre- and post-quality improvement initiative groups (early era: 2008 to 2011, n =
      15,176; later era: 2012 to 2015, n = 12,802). Focused learning sessions on PV and
      postoperative RF were undertaken in the earlier era. Incidence of death, PV, and
      RF in the two groups was analyzed using one-way analysis of variance and Fisher
      exact tests. RESULTS: The Society of Thoracic Surgeons (STS) predicted risk of
      mortality and predicted risk of mortality/morbidity were significantly higher in
      the later era (p < 0.01), as were STS predicted PV (10.1% vs 11.3%) and RF (3.4%
      vs 3.8%). Despite these increased risks, STS observed-to-expected ratios for
      mortality and mortality/morbidity fell. Observed rates for PV (10.5% vs 8.8%, p <
      0.01) and RF (3.6% vs 2.3%, p < 0.01) were associated with STS observed-to
      expected ratios of PV (1.04 vs 0.78) and RF (1.03 vs 0.60). Adjusting for case
      volume in the two eras, 271 cases of PV and 170 of RF were avoided, with
      estimated cost savings of $10,212,637 and $8,519,630, respectively. CONCLUSIONS:
      A regional collaboration using a statewide STS and an all-payor database with
      focused quality improvement is a powerful tool for change. Despite rising risks
      for mortality and morbidity, outcomes for PV and RF improved and produced
      significant cost savings. Applying these efforts nationally can enormously affect
      patient care and health care costs.

PMID- 29596825
TI  - Alterations of circular RNAs in hyperglycemic human endothelial cells.
AB  - Circular RNA (circRNA), a family of RNA generated by RNA circularization, is
      ubiquitously expressed in tissues and possesses increasingly important biological
      functions. Hyperglycemia-induced endothelial dysfunction is an initiating event
      in the pathogenesis of diabetes-associated cardiovascular complications. How high
      glucose may affect circRNAs is unknown. To address this issue, human endothelial
      cells were exposed to high glucose treatment and the changes of circRNAs were
      measured by RNA sequencing. A total 3686 circRNAs, including 1040 previously
      unrecorded circRNAs, were detected; and 95 different expression (DE) circRNAs
      were observed. The host genes of these DE circRNAs were further studied by
      function enrichment analyses. These analyses revealed genes of phosphoproteins,
      transferases, and zine finger proteins. Since circRNAs can function as a microRNA
      (miRNA) sponge, circRNAs-miRNAs interaction networks were explored by
      bioinformatics. These analyses identified a number of miRNAs, which might
      interact with DE circRNAs and play roles in the actions of high glucose on
      endothelial cells. These results demonstrate that high glucose exposure
      profoundly changes circRNA expression in endothelial cells. Altered circRNA
      expression may contribute to the effects of high glucose on endothelial function
      in diabetes.

PMID- 29596823
TI  - CXCL8 is associated with the recurrence of patients with acute myeloid leukemia
      and cell proliferation in leukemia cell lines.
AB  - Acute myeloid leukemia (AML) blasts release a wide range of chemokines in which
      CXCL8 has recently been recognized to be important for tumor progression. To find
      out the function of CXCL8 in AML, we compared blood serum of AML patients and
      healthy donors and found that the average level of CXCL8 was higher in AML
      patients. Among patients, higher expression of CXCL8 was also a positive
      recurrence indicator which illustrated the critical role of CXCL8 in AML.
      Knocking down of CXCL8 in leukemic cell lines led to significant reduction of
      proliferation via inducing G0/G1 cell cycle arrest and apoptosis, which was
      accompanied by the inactivation of ERK1/2. Furthermore, inhibition of ERK1/2 by
      specific chemical inhibitors reconstructed the CXCL8 knocking down phenomenon.
      Overall, we demonstrated that expression level of CXCL8 had a positive
      relationship with recurrence probability in AML. And CXCL8 was strongly
      implicated in AML cells growth by activating the ERK1/2 signal pathway.

PMID- 29596826
TI  - HDA9 interacts with the promoters of SOC1 and AGL24 involved in flowering time
      control in Brassica juncea.
AB  - HDA9 (a RPD3-like histone deacetylase) belongs to the histone deacetylase family
      which is involved in flowering time control through repression of AGL19 and FT,
      but it is still elusive that whether and how HDA9 directly interacts with
      flowering signal integrators of SOC1 and AGL24 in Brassica juncea. In this study,
      BjuHDA9 (a homologous HDA9) was cloned from B. juncea and ubiquitously expressed
      in root, stem, cauline leaf, flower bud and opening flower. BjuHDA9 was highly
      induced by short-day photoperiod. Yeast two-hybrid and pull-down assays
      demonstrated that BjuHDA9 could not interact with BjuSOC1 and BjuAGL24 proteins.
      Whereas, BjuHDA9 directly interacted with promoters of BjuSOC1 and BjuAGL24 via
      yeast one-hybrid and Dual-Glo(r) Luciferase assays. It suggested that the histone
      deacetylase BjuHDA9 was probably involved in flowering time control by binding to
      promoter regions of BjuSOC1 and BjuAGL24. This study will provide valuable
      information for elucidating the molecular mechanism of BjuHDA9 in regulating
      flowering time.

PMID- 29596824
TI  - Crystal structure of E. coli ZinT with one zinc-binding mode and complexed with
      citrate.
AB  - The ZnuABC ATP-binding cassette transporter found in gram-negative bacteria has
      been implicated in ensuring adequate zinc import into Zn(II)-poor environments.
      ZinT is an essential component of ZnuABC and contributes to metal transport by
      transferring metals to ZnuA, which delivers them to ZnuB in periplasmic zinc
      recruitment. Although several structures of E. coli ZinT have been reported, its
      zinc-binding sites and oligomeric state have not been clearly identified. Here,
      we report the crystal structure of E. coli ZinT at 1.76 A resolution. This
      structure contains one zinc ion in its calycin-like domain, and this ion is
      coordinated by three highly conserved histidine residues (His167, His176 and
      His178). Moreover, three oxygen atoms (O1, O6 and O7) from the citrate molecule
      interact with zinc, giving the zinc ion stable octahedral coordination. Our
      EcZinT structure shows the fewest zinc ions bound of all reported EcZinT
      structures. Crystallographic packing and size exclusion chromatography suggest
      that EcZinT prefers to form monomers in solution. Our results provide insights
      into the molecular function of ZinT.

PMID- 29596827
TI  - Structural and biochemical characterization of the type-II LOG protein from
      Streptomyces coelicolor A3.
AB  - Streptomyces coelicolor A3 contains Sc5140, a gene coding for poorly understood
      bacterial LOG-like protein. In this study, we determined the crystal structure of
      Sc5140 and found it resembles the overall structure of other type-II LOGs. In
      addition, Sc5140 exhibited phosphoribohydrolase activity against adenosine
      monophosphate (AMP), indicating that it had the same function as known type-II
      LOGs. Based on these results, we designated Sc5140 as ScLOGII. We performed
      docking calculations of AMP into the ScLOGII structure, which suggested the mode
      of binding for type-II LOG with their AMP substrate. The ScLOGII structure
      uniquely exhibited a long tail-like structure at the N-terminus that was involved
      in hexamerization of the protein; the disordered N-terminal region (DNR).
      Truncation of DNR in ScLOGII negatively affected both the phosphoribohydrolase
      activity and the oligomerization of the protein, suggesting that this region
      functioned in enzyme stabilization. However, results from truncation experiments
      using ScLOGII and CgLOGII, a type-II LOG homologue from Corynebacterium
      glutamicum, were quite different, leaving uncertainty regarding the general
      functions of DNR in type-II LOGs. Overall, the current structural work may help
      in understand the significance of type-II LOG protein at the molecular level.

PMID- 29596828
TI  - NFATc3 deficiency protects against high fat diet (HFD)-induced hypothalamus
      inflammation and apoptosis via p38 and JNK suppression.
AB  - Hypothalamic inflammation and apoptosis cause neural injury, playing an important
      role in metabolic syndrome development. Nuclear Factors of Activated T cells
      (NFATc3) show many physiological and pathological effects. However, the function
      of NFATc3 in high fat diet (HFD)-induced hypothalamus injury remains unknown. The
      wild type (WT) and NFATc3-knockout (KO) mice were subjected to HFD feeding for 16
      weeks to examine NFATc3 function in vivo. Astrocytes isolated from WT or KO mice
      were cultured and exposed to fructose (Fru) in vitro. The liver damage,
      hypothalamus injury, pro-inflammatory markers, NF-kappaB (p65), Caspase-3 and
      mitogen-activated protein kinases (MAPKs) pathways were evaluated. NFATc3 was
      significantly up-regulated in hypothalamus from mice challenged with HFD, and in
      astrocytes incubated with Fru. Both in vivo and in vitro studies indicated that
      NFATc3-deletion attenuated metabolism syndrome, reduced inflammatory regulators
      expression, inactivated NF-kappaB (p65), Caspase-3 and p38/JNK signaling pathway.
      Of note, we identified that promoting p38 or JNK activation could rescue
      inflammatory response and apoptosis in NFATc3-KO astrocytes stimulated by Fru.
      Together, these findings revealed an important role of NFATc3 NFATc3 for HFD
      induced metabolic syndrome and particularly hypothalamus injury, and
      understanding of the regulatory molecular mechanism might provide new and
      effective therapeutic strategies for prevention and treatment of hypothalamic
      damage associated with dietary obesity-associated neuroinflammation and
      apoptosis.

PMID- 29596829
TI  - Influence of acute promyelocytic leukemia therapeutic drugs on nuclear pore
      complex density and integrity.
AB  - During cell division, a large number of nuclear proteins are released into the
      cytoplasm due to nuclear envelope breakdown. Timely nuclear import of these
      proteins following exit from mitosis is critical for establishment of the G1
      nuclear environment. Dysregulation of post-mitotic nuclear import may affect the
      fate of newly divided stem or progenitor cells and may lead to cancer. Acute
      promyelocytic leukemia (APL) is a malignant disorder that involves a defect in
      blood cell differentiation at the promyelocytic stage. Recent studies suggest
      that pharmacological concentrations of the APL therapeutic drugs, all-trans
      retinoic acid (ATRA) and arsenic trioxide (ATO), affect post-mitotic nuclear
      import of the APL-associated oncoprotein PML/RARA. In the present study, we have
      investigated the possibility that ATRA and ATO affect post-mitotic nuclear import
      through interference with components of the nuclear import machinery. We observe
      reduced density and impaired integrity of nuclear pore complexes after ATRA
      and/or ATO exposure. Using a post-mitotic nuclear import assay, we demonstrate
      distinct import kinetics among different nuclear import pathways while nuclear
      import rates were similar in the presence or absence of APL therapeutic drugs.

PMID- 29596830
TI  - Liposome-encapsulated clodronate specifically depletes spinal microglia and
      reduces initial neuropathic pain.
AB  - Liposome-encapsulated clodronate (LEC) is a specific depletor of macrophages. Our
      study characterized the LEC depletory effects, given intrathecally, on spinal
      microglia and assessed its effects on initiation and maintenance of neuropathic
      pain. Measured by using the MTT assay, LEC treatment specifically inhibited cell
      viability of cultured primary microglia, but not astrocytes or neurons, from
      neonatal rats, with an IC50 of 43 MUg/mL. In spinal nerve ligation-induced
      neuropathic rats, pretreatment (1 day but not 5 days earlier) with intrathecal
      LEC specifically depleted microglia (but not astrocytes or neurons) in both
      contralateral and ipsilateral dorsal horns by the same degree (63% vs. 71%).
      Intrathecal injection of LEC reversibly blocked the antinociceptive effects of
      the GLP-1 receptor agonist exenatide and dynorphin A stimulator bulleyaconitine,
      which have been claimed to be mediated by spinal microglia, whereas it failed to
      alter morphine- or the glycine receptor agonist gelsemine-induced mechanical
      antiallodynia which was mediated via the neuronal mechanisms. Furthermore,
      intrathecal LEC injection significantly attenuated initial (one day after nerve
      injury) but not existing (2 weeks after nerve injury) mechanical allodynia. Our
      study demonstrated that LEC, given intrathecally, is a specific spinal microglial
      inhibitor and significantly reduces initiation but not maintenance of neuropathic
      pain, highlighting an opposite role of spinal microglia in different stages of
      neuropathic pain.

PMID- 29596831
TI  - The anti-tumor effect of ginsenoside Rh4 in MCF-7 breast cancer cells in vitro
      and in vivo.
AB  - Breast cancer is a tremendous threat to humans in many countries, and thus we
      need to find safe and effective drugs for treatment. Ginsenoside Rh4 has been
      reported to be present in processed ginseng. However, few studies have focused on
      its anti-tumor activity. In this study, we investigated the inhibitory effects of
      ginsenoside Rh4 on MCF-7 breast cancer cells and the pathways that promote
      apoptosis in vitro. To study the effect of ginsenoside Rh4 in vivo, xenograft
      models were randomly divided into 3 groups (the control group, 10 mg/kg/d Rh4, 20
      mg/kg/d Rh4, n = 10 per group), the ginsenoside Rh4 injection method was i.p. The
      results showed that ginsenoside Rh4 effectively inhibited proliferation, arrested
      the cell cycle in S phase and induced apoptosis in MCF-7 cells by flow cytometry.
      Morphological changes caused by ginsenoside Rh4-induced apoptosis were also
      observed by Hoechst 33342 staining. Western-blot analyses indicated that the
      apoptosis-inducing effects of ginsenoside Rh4 were associated with the external
      pathway by decreasing Bcl-2, increasing Bax, and activating caspase-8, -3 and
      PARP. Moreover, ginsenoside Rh4 significantly inhibited the growth of MCF-7 tumor
      cells in vivo. These results suggested that ginsenoside Rh4 could be a
      potentially effective anti-tumor drug for breast cancer.

PMID- 29596832
TI  - Variations in gut microbiota and fecal metabolic phenotype associated with
      Fenbendazole and Ivermectin Tablets by 16S rRNA gene sequencing and LC/MS-based
      metabolomics in Amur tiger.
AB  - BACKGROUND: The Amur tiger is one of the most endangered species in the world,
      and the healthy population of captive Amur tigers assists the recovery of the
      wild population. Gut microbes have been shown to be important for human disease
      and health, but little research exists regarding the microbiome of Amur tigers in
      captivity. METHODS: In this study, we used an integrated approach of 16S rRNA
      gene sequencing combined with ultra-high-performance liquid chromatography-mass
      spectrometry (UHPLC-MS)-based metabolomics to analyze the effects of Fenbendazole
      and Ivermectin Tablets on the gut microbiota and fecal metabolic phenotype of the
      Amur tiger. RESULTS: The relative abundances of the bacterial genera Collinsella,
      Clostridium XI and Megamonas were decreased, whereas those of Escherichia and
      Clostridium sensu stricto were increased in experimental Amur tigers compared
      with those in normal controls. Meanwhile, distinct changes in the fecal metabolic
      phenotype of the experimental Amur tigers were also found, including lower levels
      of acrylic acid, acetoacetate and catechol and higher amounts of 5,6
      dihydrouracil, adenine hydrochloride hydrate and galactitol. Moreover, the
      differentially abundant gut microbes were substantially associated with the
      altered fecal metabolites, especially the bacteria in the Firmicutes and
      Actinomycetes, which were involved in the metabolism of 5,6-dihydrouracil, 6
      phospho-d-gluconate and 1-methylnicotinamide. CONCLUSION: Our results indicate
      for the first time that Fenbendazole and Ivermectin Tablets not only disturb the
      gut microbiota at the abundance level but also alter the metabolic homeostasis of
      the Amur tiger.

PMID- 29596833
TI  - A novel TBX1 missense mutation in patients with syndromic congenital heart
      defects.
AB  - Congenital heart defects represent a characteristic part of several genetic
      syndromes associated with chromosomal abnormalities such as 22q11.2 deletion
      syndrome; many genes located in this locus, mainly TBX1, are candidate genes for
      congenital heart defects. In our cohort of 27 subjects with congenital heart
      defect, both karyotype analysis and Fluorescence in situ hybridization (FISH)
      were performed. The TBX1 gene was sequenced in patients lacking chromosomal
      abnormalities. FISH analysis showed a de novo 22q11.2 deletion in two patients.
      The screening of TBX1 coding sequence identified a novel missense mutation c.569C
      > A (p.P190Q) in six unrelated patients and detected two associated known single
      nucleotide polymorphisms; the c.664C > T (rs2301558) in three patients and the
      c.420T > C (p.Phe140 Phe) (rs41298814) in one patient. Bioinformatic tools show
      that the novel missense mutation c.569C > A could modify the function and the
      stability of the TBX1 protein. The c.569C > A mutation was not found in 50
      healthy controls. Ours results suggest a deleterious role of the c.569C > A
      mutation and strengthen the hypothesis that this mutation might be responsible
      for the same phenotype spectrum as the 22q11.2 deletion syndrome.

PMID- 29596834
TI  - AZD5153, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth
      in vitro and in vivo.
AB  - The development of novel anti-papillary thyroid carcinoma agents is urgent.
      AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4)
      inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival,
      proliferation and cell cycle progression in TPC-1 cells and primary human thyroid
      carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial
      cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and
      primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly
      attenuated with co-treatment of the caspase inhibitors. BRD4 expression was
      elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the
      thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and
      cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1
      and primary cancer cells. In vivo, oral administration of AZD5153 at well
      tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined
      immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1,
      were also downregulated in AZD5153-treated tumor tissues. Collectively, the
      results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma
      cell growth in vitro and in vivo.

PMID- 29596835
TI  - TNF receptor associated factor 5 controls oncostatin M-mediated lung
      inflammation.
AB  - Oncostatin M (OSM) is involved in pathogenesis of several human inflammatory
      diseases including lung inflammation and fibrosis. Although accumulating evidence
      indicates that OSM mediates lung inflammation, the precise mechanism for OSM on
      lung inflammation still remains unclear. In this study, we found that OSM
      receptor was abundantly expressed on endothelial and stromal/fibroblast cells in
      the lung of mice. In vitro stimulation with OSM upregulated vascular cell
      adhesion molecule-1 (VCAM-1), which promotes eosinophil infiltration in the lung
      tissues, on freshly-isolated lung stromal/fibroblast cells from wild-type mice.
      However, these cells from TNF receptor associated factor 5 (TRAF5)-deficient mice
      failed to show the increase in VCAM-1 expression after OSM stimulation.
      Furthermore, Traf5-/- mice showed markedly attenuated lung inflammation in terms
      of eosinophil infiltration upon intranasal administration with OSM as compared to
      wild-type mice. These results indicate that TRAF5 is crucially involved in OSM
      mediated lung inflammation probably by inducing lung stromal/fibroblast cell
      activation.

PMID- 29596836
TI  - Radiation resistance of the lung adenocarcinoma is related to the AKT-Onzin
      POU5F1 axis.
AB  - Non-small cell lung carcinoma is the predominant type of lung cancer, and shows
      an easily developable tolerance to radiotherapy. Cancer stem cells are suggested
      to be involved in the resistance against therapies. Onzin might be accumulated
      during the process tumor overcoming the radiation stress. To address the
      relationship between Onzin, stemness and radiation resistance, we treated the
      lung cancer tumor bearing mice with radiaotherapy and observed the differences
      between radiation sensitive (RS) and resistant (RR) tumors. Immunohistochemistry
      and HE staining were used to observe Onzin and POU5F1 expression in tumor
      tissues. Quantitative realtime-PCR and Western blot were applied for Onzin and
      POU5F1 in tumors and cells. In-vitro cellular viability was assessed by CCK8
      methods for tumor derived cells. The stably transfected A549 cell lines
      overexpressing Onzin were generated through lentivirus transfection. After
      radiotherapy, those RR adenocarcinoma tumors and cells derived from them showed
      an increased Onzin expression. Further, RR cells were found upregulated stemness,
      indicated by increased sphericity and proliferation, as well as POU5F1
      expression. Next, we overexpressed Onzin in the A549 cells and found an elevated
      POU5F1 expression, increased proliferation, and enhanced sphericity. Moreover,
      this could be suppressed by the AKT inhibitor MK-2260. In vivo, the A549 cells
      overexpressing Onzin showed not only higher tumor formation capability and
      growth, but also a significant resistance to radiation. Taken together, RR tumors
      have upregulated Onzin and POU5F1 expression. Ectopic expression of Onzin
      promotes the POU5F1 expression as well as stemness functions, and confers
      adenocarcinomas the resistance to radiotherapy.

PMID- 29596837
TI  - Lipidomics biomarker studies: Errors, limitations, and the future.
AB  - Lipidomics is an ever-expanding subfield of metabolomics that surveys 3000 to
      5000 individual lipids across more than 56 lipid subclasses, including lipid
      peroxidation products. Unfortunately, there exists a large number of publications
      with poor quality data obtained with unit mass resolution leading to many lipid
      misidentifications. This is further complicated by poor scientific oversight with
      regard to recognition of isobar issues, sample collection, and sample storage
      issues that inexplicably requires more detailed attention. Inadvertent or
      intentional obfuscation of relative quantification data represented as absolute
      quantification is a subtle but profound difference that may readers outside of
      the field may not realize, therefore, instigating disservice and unnecessary
      distrust in the scientific community. These issues need to be addressed
      aggressively as high quality data are essential for the translation of biomarker
      research to clinical practice.

PMID- 29596839
TI  - Hepatitis D diagnostics:Utilization and testing in the United States.
AB  - Hepatitis D virus (HDV) infection may accompany acute or chronic hepatitis B
      virus infection. While HDV infection in the United States is thought to be
      uncommon, there are limited data regarding frequency of testing, and prevalence
      of HDV antibody and HDV RNA. We evaluated the use of HDV antibody testing using
      electronic medical record (EMR) data. Among 1007 HBsAg positive patients, only
      121 had been tested for HDV antibody. Testing was performed primarily by
      gastroenterologists/hepatologists and limited testing was performed in
      identifiable high risk groups including those with HBV/HIV coinfection. Overall,
      HDV antibody was detected in 3.3% (95% C.I. = 0.9%-8.2%) An HDV RNA assay was
      developed and validated and 138 HBV or HBV/HIV coinfected patients were tested.
      The prevalence of HDV among the HBV/HIV coinfected subjects was 2.2% (95% C.I. =
      0-5.3%). In a U.S. Midwestern population of HBV infected patients, HDV testing is
      under-employed. Overall prevalence exceeds 2% whether testing by antibody or HDV
      RNA and more comprehensive HDV surveillance may be indicated.

PMID- 29596838
TI  - CSN5/Jab1 facilitates non-small cell lung cancer cell growth through stabilizing
      survivin.
AB  - CSN5/JAB1 is a critical subunit of the COP9 signalosome (CSN) and is essentially
      involved in diverse types of cancer, but little is known about the role of CSN5
      in non-small cell lung cancer (NSCLC). In the current study, we found that CSN5
      expression was higher in NSCLC tissues compared to the corresponding non-tumor
      tissues. High CSN5 expression level is closely correlated with tumor progression
      and poor survival in NSCLC patients. We also found that knockdown of CSN5
      remarkably suppressed cell growth by inducing cell cycle arrest and apoptosis
      promotion in NSCLC cells. Mechanistic investigations revealed that CSN5 directly
      bound survivin and decreased its ubiquitination to enhance the protein stability
      of survivin. Additionally, our results confirmed that the tumor-promoting effects
      of CSN5 in NSCLC cells is at least partly through stabilization of survivin.
      Overall, our data suggested that CSN5 functions as an oncogenic gene in NSCLC,
      which could be a potential diagnostic and therapeutic target for NSCLC.

PMID- 29596840
TI  - Reduced Abd-B Hox function during kidney development results in lineage
      infidelity.
AB  - Hox genes can function as key drivers of segment identity, with Hox mutations in
      Drosophila often resulting in dramatic homeotic transformations. In addition,
      however, they can serve other essential functions. In mammals, the study of Hox
      gene roles in development is complicated by the presence of four Hox clusters
      with a total of 39 genes showing extensive functional overlap. In this study, in
      order to better understand shared core Hox functions, we examined kidney
      development in mice with frameshift mutations of multiple Abd-B type Hox genes.
      The resulting phenotypes included dramatically reduced branching morphogenesis of
      the ureteric bud, premature depletion of nephron progenitors and abnormal
      development of the stromal compartment. Most unexpected, however, we also
      observed a cellular level lineage infidelity in nephron segments. Scattered cells
      within the proximal tubules, for example, expressed genes normally expressed only
      in collecting ducts. Multiple combinations of inappropriate nephron segment
      specific marker expression were found. In some cases, cells within a tubule
      showed incorrect identity, while in other cases cells showed ambiguous character,
      with simultaneous expression of genes associated with more than one nephron
      segment. These results give evidence that Hox genes have an overlapping core
      function at the cellular level in driving and/or maintaining correct
      differentiation decisions.

PMID- 29596842
TI  - More than a syllable in fib-ROS-is: The role of ROS on the fibrotic extracellular
      matrix and on cellular contacts.
AB  - Fibrosis is characterized by excess deposition of extracellular matrix (ECM).
      However, the ECM changes during fibrosis not only quantitatively but also
      qualitatively. Thus, the composition is altered as the expression of various ECM
      proteins changes. Moreover, also posttranslational modifications, secretion,
      deposition and crosslinkage as well as the proteolytic degradation of ECM
      components run differently during fibrosis. As several of these processes involve
      redox reactions and some of them are even redox-regulated, reactive oxygen
      species (ROS) influence fibrotic diseases. Redox regulation of the ECM has not
      been studied intensively, although evidences exist that the alteration of the
      ECM, including the redox-relevant processes of its formation and degradation, may
      be of key importance not only as a cause but also as a consequence of fibrotic
      diseases. Myofibroblasts, which have differentiated from fibroblasts during
      fibrosis, produce most of the ECM components and in return obtain important
      environmental cues of the ECM, including their redox-dependent fibrotic
      alterations. Thus, myofibroblast differentiation and fibrotic changes of the ECM
      are interdependent processes and linked with each other via cell-matrix contacts,
      which are mediated by integrins and other cell adhesion molecules. These cell
      matrix contacts are also regulated by redox processes and by ROS. However, most
      of the redox-catalyzing enzymes are localized within cells. Little is known about
      redox-regulating enzymes, especially the ones that control the formation and
      cleavage of redox-sensitive disulfide bridges within the extracellular space.
      They are also important players in the redox-regulative crosstalk between ECM and
      cells during fibrosis.

PMID- 29596843
TI  - Viability assessment of primary growth oocytes following ovarian tissue
      vitrification of neotropical teleost pacu (Piaractus mesopotamicus).
AB  - Vitrification of ovarian tissue containing immature oocytes provides an important
      tool for protecting the endangered species and genetic diversity in aquatic
      species. Therefore, the main objective was to assess primary growth (PG) oocytes
      viability following ovarian tissue vitrification using histological analysis, two
      staining protocols (trypan blue or fluorescein diacetate combined with propidium
      iodide) and mitochondrial activity assay (MTT assay). In addition, oocyte
      histomorphometry was performed to evaluate the morphometric parameters after
      vitrification and the relationship with the occurrence of damage (nucleus and/or
      membrane) in PG oocytes. There was no significant difference among the vitrified
      oocytes using trypan blue dye or FDA + IP staining. Oocyte viability assessed
      using histological analysis showed that vitrification solution 2.0 M Me2SO + 2.5
      M etilenoglycol +0.5 M sucrose (VS3; 66.43 +/- 4.68%) and 1.5 M methanol + 5.5 M
      Me2SO + 0.5 M sucrose (VS5; 74.14 +/- 3.71%) had the lowest viability rate.
      Similar results were observed in MTT assay where VS3 (1.63 +/- 0.12) and VS5
      (1.58 +/- 0.09) had the lowest averages when compare with VS1 (2.39 +/- 0.14),
      VS2 (1.78 +/- 0.06) and VS4 (2.34 +/- 0.19) (P = 0.0002). In membrane damage
      evaluation by histology, there was no difference among vitrified oocytes and
      control. However, the highest percentages of nucleus damage were observed in
      treatments VS3 (26.00 +/- 5.55) and VS5 (26.00 +/- 5.55). Oocyte diameter did not
      change after vitrification; however, nucleus diameter was significantly higher in
      control group (49.03 +/- 1.07). Oocyte viability by histological analysis was
      positive-correlated to the occurrence of nucleus (r2 = 0.78) and membrane (r2 =
      0.45) damage after vitrification/warming. The high viability of PG oocytes
      obtained after ovarian tissue vitrification of Piaractus mesopotamicus suggests
      that the protocol applied here might be used successfully in other teleost
      species for food production.

PMID- 29596841
TI  - miR-206 is required for changes in cell adhesion that drive muscle cell
      morphogenesis in Xenopus laevis.
AB  - MicroRNAs (miRNAs) are highly conserved small non-coding RNA molecules that post
      transcriptionally regulate gene expression in multicellular organisms. Within the
      set of muscle-specific miRNAs, miR-206 expression is largely restricted to
      skeletal muscle and is found exclusively within the bony fish lineage. Although
      many studies have implicated miR-206 in muscle maintenance and disease, its role
      in skeletal muscle development remains largely unknown. Here, we examine the role
      of miR-206 during Xenopus laevis somitogenesis. In Xenopus laevis, miR-206
      expression coincides with the onset of somitogenesis. We show that both knockdown
      and over-expression of miR-206 result in abnormal somite formation affecting
      muscle cell rotation, attachment, and elongation. In particular, our data
      suggests that miR-206 regulates changes in cell adhesion that affect the ability
      of newly formed somites to adhere to the notochord as well as to the intersomitic
      boundaries. Additionally, we show that beta-dystroglycan and F-actin expression
      levels are significantly reduced, suggesting that knockdown of miR-206 levels
      affects cellular mechanics necessary for cell shape changes and attachments that
      are required for proper muscle formation.

PMID- 29596844
TI  - Molecular pathology of Multiple Sclerosis lesions reveals a heterogeneous
      expression pattern of genes involved in oligodendrogliogenesis.
AB  - Little is known about the decisive molecular factors that regulate lesion
      remyelination in Multiple Sclerosis. To identify such factors, we performed a
      differential gene expression analysis of normal appearing white matter (NAWM),
      active, remyelinating, and inactive demyelinated lesions. As expected, many genes
      involved in inflammatory processes were detected to be differentially regulated
      between these tissue types. Among them, we found an increased expression of
      members of the STAT6 pathway such as STAT6, IL4 and IL4R in active, remyelinated
      and inactive demyelinated lesions. This suggests that a protective, anti
      inflammatory reaction, as already reported to be present in MS NAWM, is further
      enhanced in lesion tissues. Focusing on genes influencing oligodendrogliogenesis,
      we found a decreased expression of NKX2-2 in active, remyelinated and inactive
      demyelinated lesions, whereas SOX10 was downregulated in inactive demyelinated
      lesions, when compared to NAWM. Simultaneously, CXCL12 (SDF1) expression was
      strongly increased in active, remyelinated and inactive demyelinated lesions, but
      increased expression of the IGF1 and IGF2 genes was found in inactive
      demyelinated lesions. This demonstrates that, in principle, expression of genes
      promoting oligodendrogliogenesis occurs in MS lesion tissue - even in inactive
      demyelinated lesions. In contrast, oligodendrogenesis inhibiting genes such as
      JAG1 were also expressed at higher levels in inactive demyelinated lesions. Both,
      oligodendrogliogenesis promoting as well as inhibiting genes are expressed in all
      lesion tissues. However, no clear promoting or inhibiting expression pattern
      could be detected in any of the different types of lesioned tissues. This might
      reflect the heterogeneity of lesion development in MS patients, both in terms of
      mechanisms and temporal differences.

PMID- 29596846
TI  - Event monitoring: Can we detect more than one event at a time?
AB  - A prior study by Wu and Wolfe found that the capacity for event monitoring (e.g.
      did an item change its state?) is more limited than for classic multiple object
      tracking. That limited capacity, K, could arise from either of two situations. It
      could be that people can detect K events simultaneously or it could be that they
      can successfully detect just one event at a time while monitoring K out of a
      total of N items. In the three different experiments of the present study,
      observers were asked to monitor a set of moving objects while watching for two
      critical events occurring in that set. Observers' performance can be well
      described by a model that includes an ability to detect two changes at once. Our
      results suggest that the capacity for event monitoring is further limited when
      tracking an additional event, but within the monitored set, people can detect at
      least two events simultaneously.

PMID- 29596845
TI  - Spontaneous respiratory plasticity following unilateral high cervical spinal cord
      injury in behaving rats.
AB  - Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord
      injury (SCI) for studying respiratory dysfunction and plasticity. However, most
      previous studies were performed under anesthesia, which significantly alters
      respiratory network. Therefore, the goal of this work was to assess spontaneous
      diaphragm recovery post-C2Hx in awake, freely behaving animals. Adult rats were
      chronically implanted with diaphragm EMG electrodes and recorded during 8 weeks
      post-C2Hx. Our results reveal that ipsilateral diaphragm activity partially
      recovers within days post-injury and reaches pre-injury amplitude in a few weeks.
      However, the full extent of spontaneous ipsilateral recovery is significantly
      attenuated by anesthesia (ketamine/xylazine, isoflurane, and urethane). This
      suggests that the observed recovery may be attributed in part to activation of
      NMDA receptors which are suppressed by anesthesia. Despite spontaneous recovery
      in awake animals, ipsilateral hemidiaphragm dysfunction still persists: i)
      Inspiratory bursts during basal (slow) breathing exhibit an altered pattern, ii)
      the amplitude of sighs - or augmented breaths - is significantly decreased, and
      iii) the injured hemidiaphragm exhibits spontaneous events of hyperexcitation.
      The results from this study offer an under-appreciated insight into spontaneous
      diaphragm activity and recovery following high cervical spinal cord injury in
      awake animals.

PMID- 29596847
TI  - An academic debate: OnabotulinumtoxinA for chronic migraine: PREEMPT-derived vs
      "customized" dosing/injection paradigm.
AB  - In 2010 onabotulinumtoxinA (OnabotA) was approved by the United States Food and
      Drug Administration for the treatment of chronic migraine (CM). Data supporting
      approval were derived primarily from two parallel placebo-controlled trials, the
      PREEMPT studies. Many clinicians and research investigators critical of those
      data have recommended that the dosing/injection paradigm for treating CM be
      "customized" to the needs of the individual patient rather than administered in a
      uniform fashion conforming to the methodology utilized in the PREEMPT studies. In
      this paper the authors debate the issue of whether treatment of CM with OnabotA
      should be standardized versus customized.

PMID- 29596848
TI  - Isolation and characterization of toxins from Xenorhabdus nematophilus against
      Ferrisia virgata (Ckll.) on tuberose, Polianthes tuberosa.
AB  - This study was aimed to evaluate the toxins of Xenorhabdus nematophilus bacterial
      isolate MDUStBa15 isolated from the nematode Steinernema carpocapsae that can
      parasitize two tailed mealybug Ferrisia virgata which is a new pest on tuberose.
      Soluble protein and organic fractions were characterized from cell free extract
      of X. nematophilus. Using SDS PAGE, presence of low molecular weight toxic
      proteins (12, 42 and 60 kDa) was observed in cell free extracts of X.
      nematophilus. Among these three proteins, 12 kDa was newly found in this study
      which showed anti-feedant activity and the maximum of 87.50% and 82.50% mortality
      of crawlers and adults of F. virgata, respectively at 72 h after treatment. GC-MS
      analysis of culture filtrates revealed the presence of five major compounds, all
      are exhibiting insecticidal property. Among several organic fractions, 1, 4 -
      epoxynaphthalene - 1 (2H) - methanol, 4,5,7-tris (1,1 - dimethylethyl) - 3,4 -
      dihydro; Pentacosane and Hexacosane were found in this study. Pot culture study
      revealed that an optimum dose of 5 ml/l of crude toxin caused the maximum
      mortality in crawlers (100%) and in adults (96.8%) of F. virgata at 72 h after
      spraying. In a field study application of 5 ml/l crude toxin along with
      biocontrol agent (Ladybird beetle - Cryptolaemus montrouzieri) registered the
      90.55% mortality in crawlers and 73.60% mortality in adults of F. virgata at 7
      days after spraying. The present study provides the clear evidence for the
      toxicity of protein; organic fraction and crude toxin which was obtained from X.
      nematophilus isolate MDUStBa15 against F. virgata on tuberose both in lab and
      field conditions. Hence, it can be utilised to manage the F. virgata on tuberose.

PMID- 29596849
TI  - Histochemical characteristics of regressing vessels in the hyaloid vascular
      system of neonatal mice: Novel implication for vascular atrophy.
AB  - The hyaloid vasculature constitutes a transitory system nourishing the internal
      structures of the developing eye, but the mechanism of vascular regression and
      its cell biological characteristics are not fully understood. The present study
      aimed to reveal the specificity of the hyaloid vessels by a systematic
      immunohistochemical approach for marker substances of myeloid cells and the
      extracellular matrix (ECM) in neonatal mice. Macrophages immunoreactive for
      F4/80, cathepsin D, and LYVE-1 gathered around the vasa hyaloidea propria (VHP),
      while small round cells in vascular lumen of VHP were selectively immunoreactive
      for galectin-3; their segmented nuclei and immunoreactivities for Ly-6G, CD11b,
      and myeloperoxidase indicated their neutrophilic origin. VHP possessed thick ECM
      and a dense pericyte envelope as demonstrated by immunostaining for laminin, type
      IV collagen, integrin beta1, and NG2. The galectin-3+ cells loosely aggregated
      with numerous erythrocytes in the lumen of hyaloid vessels in a manner
      reminiscent of vascular congestion. Galectin-3 is known to polymerize and form a
      complex with ECM and NG2 as well as recruit leukocytes on the endothelium.
      Observation of galectin-3 KO mice implicated the involvement of galectin-3 in the
      regression of hyaloid vasculature. Since macrophages may play central roles
      including blocking of the blood flow and the induction of apoptosis in the
      regression, galectin-3+ neutrophils may play a supportive role in the macrophage
      mediated involution of the hyaloid vascular system.

PMID- 29596850
TI  - Posterior stromal cell apoptosis triggered by mechanical endothelial injury and
      basement membrane component nidogen-1 production in the cornea.
AB  - This study was performed to determine whether cells in the posterior stroma
      undergo apoptosis in response to endothelial cell injury and to determine whether
      basement membrane component nidogen-1 was present in the cornea. New Zealand
      White rabbits had an olive tip cannula inserted into the anterior chamber to
      mechanically injure corneal endothelial cells over an 8 mm diameter area of
      central cornea with minimal injury to Descemet's membrane. At 1 h (6 rabbits) and
      4 h (6 rabbits) after injury, three corneas at each time point were cryopreserved
      in OCT for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
      assay and immunohistochemistry (IHC) for vimentin and nidogen-1, and three
      corneas at each time point were fixed for transmission electron microscopy (TEM).
      Uninjured corneas were controls. Stromal cells over approximately the posterior
      25% of the stroma overlying to the site of corneal endothelial injury underwent
      apoptosis detected by the TUNEL assay. Many of these apoptotic cells were
      vimentin+, suggesting they were likely keratocytes or corneal fibroblasts.
      Stromal cells peripheral to the site of endothelial injury and more anterior
      stromal cells overlying the site of endothelial injury did not undergo apoptosis.
      Stromal cell death was confirmed to be apoptosis by TEM. No apoptosis of stromal
      cells was detected in control, uninjured corneas. Nidogen-1 was detected in the
      stroma of unwounded corneas, with higher nidogen-1 in the posterior stroma than
      the anterior stroma. After endothelial scrape injury, concentrations of nidogen-1
      appeared to be in the extracellular matrix of the posterior stroma and, possibly,
      within apoptotic bodies of stromal cells. Thus, posterior stromal cells, likely
      including keratocytes, undergo apoptosis in response to corneal endothelial
      injury, analogous to anterior keratocytes undergoing apoptosis in response to
      epithelial injury.

PMID- 29596852
TI  - Homeostasis despite instability.
AB  - We have shown previously that different homeostatic mechanisms in biochemistry
      create input-output curves with a "chair" shape. At equilibrium, for intermediate
      values of a parameter (often an input), a variable, Z, changes very little (the
      homeostatic plateau), but for low and high values of the parameter, Z changes
      rapidly (escape from homeostasis). In all cases previously studied, the steady
      state was stable for each value of the input parameter. Here we show that, for
      the feedback inhibition motif, stability may be lost through a Hopf bifurcation
      on the homeostatic plateau and then regained by another Hopf bifurcation. If the
      limit cycle oscillations are relatively small in the unstable interval, then the
      variable Z maintains homeostasis despite the instability. We show that the
      existence of an input interval in which there are oscillations, the length of the
      interval, and the size of the oscillations depend in interesting and complicated
      ways on the properties of the inhibition function, f, the length of the chain,
      and the size of a leakage parameter.

PMID- 29596851
TI  - Gills specific type 2 crustin isoforms: Its molecular cloning and
      characterization from kuruma shrimp Marsupenaeus japonicus.
AB  - Crustins are diverse group of antimicrobial peptides (AMPs) that have numerous
      isoforms mainly identified from hemocytes in decapods crustacean. However, little
      is known about its presence solely in gills tissue. In this study, we found two
      new crustin isoforms MjCRS8 and MjCRS9 by using transcriptome analysis from
      gills. Open reading frame of MjCRS8 and MjCRS9 were 593 bp and 459 bp encoding
      197aa and 152aa, respectively. Tissue distribution analysis indicated that both
      MjCRS8 and MjCRS9 are expressed only in gills tissue. Multiple sequence alignment
      and phylogenetic analysis with previously reported crustin suggested that both
      MjCRS8 and MjCRS9 belong to type 2 crustin family. Experimental infection was
      conducted against Vibrio parahaemolyticus and white spot syndrome virus (WSSV) by
      immersion test. However, no significant upregulation was observed.

PMID- 29596853
TI  - Exenatide has a pronounced effect on energy intake but not energy expenditure in
      non-diabetic subjects with obesity: A randomized, double-blind, placebo
      controlled trial.
AB  - AIMS: Exenatide is a glucagon-like peptide 1 (GLP-1) mimetic which induces weight
      loss predominantly, it is presumed, via decreased food intake. However,
      circulating GLP-1 is also a determinant of energy expenditure. We sought to
      quantify the effect of exenatide on energy expenditure (EE) and energy intake.
      MATERIALS AND METHODS: In this single-center, randomized double-blind placebo
      controlled trial, we randomized 80 healthy, non-diabetic volunteers with obesity
      (46 women, age: 34.4 +/- 8.7 y, body fat by DXA: 44.2 +/- 7.8%) to subcutaneous
      exenatide 10 MUg twice daily or placebo. Subjects were admitted to our clinical
      research unit for measurement of 24 h-EE in a whole-room indirect calorimeter and
      ad libitum food intake using an automated vending machine paradigm before and
      after randomization. Furthermore, energy expenditure and ad libitum food intake
      measures were repeated at 24-week after readmission for 7-day inpatient stay.
      Body weight was obtained weekly for up to 5 weeks and was recorded at each
      monthly follow up visit up to 24 weeks. RESULTS: Prior to randomization,
      participants over ate during the 3-day vending machine period in the whole study
      group (114.6 +/- 35.2%), expressed as percentage of weight maintaining energy
      needs (WMEN) with those who were eventually randomized to exenatide overeating
      more (121.6 +/- 37.7%) compared to placebo group (107.6 +/- 31.5%). In the
      exenatide group, ad libitum absolute energy intake decreased by 1016.1 +/- 724.5
      kcal/day (95% CI: -1250.9 to -781.2) versus a 245.1 +/- 710.5 kcal/day (95% CI: 
      475.4 to -14.7) decrease in placebo (Delta = -624.8 Kcal/day, p < 0.0001) whereas
      the reduction in ad libitum caloric intake relative to WMEN was a more modest
      366.8 +/- 752.1 kcal/day (95% CI: -614.0 to -119.6) decrease compared to 8.0 +/-
      860.1 kcal/day (95% CI: -286.8 to 270.8) reduction in placebo (Delta = -382.3
      Kcal/day, p = 0.03). The decrease was uniform across all macronutrients groups.
      No differences in 24hEE or substrate oxidation rates were found. In the exenatide
      group, body weight decreased more over the 5 weeks (beta = -0.039 kg/week, p =
      0.02) and was lower compared to placebo at the end of fifth week (-1.48 +/- 0.77
      kg; 95% CI: -3.02 to 0.05, p = 0.06). At the 24-week follow up, there was no
      difference in energy intake between exenatide group and placebo group and the
      treatment group decreased 24-h EE more compared to placebo (beta = -160.6
      Kcal/day, 95% CI: -307.6 to 13.6, p = 0.03) compared to their pre-randomization
      measurement. However, this reduction was not present after adjustment for changes
      in FM and FFM (beta = -87 kcal/day, p = 0.14). No difference was observed in body
      weight (Delta = -1.72 kg, 95% CI: -5.77 to 2.30, p = 0.39) in exenatide versus
      placebo over 24 weeks. CONCLUSION: Compared with placebo, exenatide decreased
      early ad libitum energy intake but did not change 24 h-EE. However, the reduction
      was more modest in relative versus absolute terms (i.e. below that needed for
      WMEN). Thus, although rate of weight change was greater in the exenatide treated
      subjects at 5 weeks, the absolute difference in weight was not significant. These
      findings indicate that although exenatide reduces food intake, it may be more
      beneficial in blunting overeating and thus may serve to more prevent weight
      regain following initial weight loss.

PMID- 29596855
TI  - Simple method for assembly of CRISPR synergistic activation mediator gRNA
      expression array.
AB  - When studying complex interconnected regulatory networks, effective methods for
      simultaneously manipulating multiple genes expression are paramount. Previously,
      we have developed a simple method for generation of an all-in-one CRISPR gRNA
      expression array. We here present a Golden Gate Assembly-based system of
      synergistic activation mediator (SAM) compatible CRISPR/dCas9 gRNA expression
      array for the simultaneous activation of multiple genes. Using this system, we
      demonstrated the simultaneous activation of the transcription factors, TWIST,
      SNAIL, SLUG, and ZEB1 a human breast cancer cell line.

PMID- 29596854
TI  - Brain and behavioral correlates of insulin resistance in youth with depression
      and obesity.
AB  - Depression, together with insulin resistance, is increasingly prevalent among
      youth. These conditions have traditionally been compartmentalized, but recent
      evidence suggests that a shared brain motivational network underlies their co
      occurrence. We posit that, in the context of depressive symptoms, insulin
      resistance is associated with aberrant structure and functional connectivity in
      the Anterior Cingulate Cortex (ACC) and hippocampus. This motivational neural
      circuit underlies dysfunctional behavioral responses and increased sensitivity to
      rewarding aspects of ingesting high calorie food that lead to disinhibition of
      eating even when satiated. To investigate this shared mechanism, we evaluated a
      sample of forty-two depressed and overweight (BMI > 85th%) youth aged 9 to 17.
      Using ACC and hippocampus structural and seed-based regions of interest, we
      investigated associations between insulin resistance, depression, structure (ACC
      thickness, and ACC and hippocampal area), and resting-state functional
      connectivity (RSFC). We predicted that aberrant associations among these neural
      and behavioral characteristics would be stronger in insulin resistant compared to
      insulin sensitive youth. We found that youth with greater insulin resistance had
      higher levels of anhedonia and more food seeking behaviors, reduced hippocampal
      and ACC volumes, and greater levels of ACC and hippocampal dysconnectivity to
      fronto-limbic reward networks at rest. For youth with high levels of insulin
      resistance, thinner ACC and smaller hippocampal volumes were associated with more
      severe depressive symptoms, whereas the opposite was true for youth with low
      levels of insulin resistance. The ACC-hippocampal motivational network that
      subserves depression and insulin resistance separately, may represent a critical
      neural interaction that link these syndromes together.

PMID- 29596857
TI  - Inversion effects for faces and objects in developmental prosopagnosia: A case
      series analysis.
AB  - The disproportionate face inversion effect (dFIE) concerns the finding that face
      recognition is more affected by inversion than recognition of non-face objects;
      an effect assumed to reflect that face recognition relies on special operations.
      Support for this notion comes from studies showing that face processing in
      developmental prosopagnosia (DP) is less affected by inversion than it is in
      normal subjects, and that DPs may even display face inversion superiority
      effects, i.e. better processing of inverted compared to upright faces. To date,
      however, there are no reports of direct comparisons between inversion effects for
      faces and objects, investigating whether the altered inversion effect in DP is
      specific to faces. We examined this question by comparing inversion effects for
      faces and cars in two otherwise identical recognition tasks in a group of DPs (N
      = 16) and a matched control group, using a case series design. Although both
      groups showed inversion effects for both faces and cars, only the control group
      exhibited a significant dFIE, i.e. a larger inversion effect for faces than cars.
      In comparison, the DPs were not significantly more affected by inversion than the
      control group when assessed with a face processing task that did not require
      recognition. Importantly, in both settings the DPs are better with upright than
      with inverted faces, and on the individual level no DP was found to perform
      significantly better with inverted than with upright faces. In fact, the DPs are
      impaired relative to the control group with both upright and inverted faces and
      to a less extent also with upright and inverted cars. These results yield no
      evidence of inversion superiority in DP but rather suggest that their face
      recognition problem is not limited to operations specialized for upright faces.

PMID- 29596856
TI  - Neural signatures of Trail Making Test performance: Evidence from lesion-mapping
      and neuroimaging studies.
AB  - The Trail Making Test (TMT) is an extensively used neuropsychological instrument
      for the assessment of set-switching ability across a wide range of neurological
      conditions. However, the exact nature of the cognitive processes and associated
      brain regions contributing to the performance on the TMT remains unclear. In this
      review, we first introduce the TMT by discussing its administration and scoring
      approaches. We then examine converging evidence and divergent findings concerning
      the brain regions related to TMT performance, as identified by lesion-symptom
      mapping studies conducted in brain-injured patients and functional magnetic
      resonance imaging studies conducted in healthy participants. After addressing
      factors that may account for the heterogeneity in the brain regions reported by
      these studies, we identify future research endeavours that may permit
      disentangling the different processes contributing to TMT performance and
      relating them to specific brain circuits.

PMID- 29596858
TI  - A novel histochemical method of simultaneous detection by a single- or double
      immunofluorescence and Bielschowsky's silver staining in teased rat sciatic
      nerves.
AB  - BACKGROUND: The Golgi silver method has been widely used in neuroscience for the
      study of normal and pathological morphology of neurons. The method has been
      steadily improved and Bielschowsky's silver staining method (BSSM) is widely used
      in various pathological conditions, like Alzheimer's disease. NEW METHOD: In this
      work, teased sciatic nerves were silver impregnated using BSSM. We also developed
      simultaneous staining by silver impregnation and single- or double
      immunofluorescence of the same section in teased nerve preparations. We
      immunostained against non-myelinating Schwann cells and different myelinating
      Schwann cell domains. RESULTS: BSSM teased nerves show a strong staining of axons
      (black) and a gold-brown staining of myelinating and non-myelinating Schwann
      cells. We were also able to stain by immunofluorescence these BSSM teased nerves
      with specific molecular markers against non-myelinating Schwann cells, also
      against non-compact myelin such as the Schmidt-Lanterman incisures or paranodal
      regions and compact myelin, but not axons. COMPARISON WITH EXISTING METHODS AND
      CONCLUSIONS: In peripheral nerves, several silver impregnation methods have been
      used to stain nerves in paraffin sections, but not in teased nerves to enable the
      assessment of isolated nerve fibers. In conclusion, BSSM gives accurate
      information of nerve morphology and combining the procedure with
      immunofluorescence it would be very useful to study the molecular nerve domain
      organization of the nerve fibers, and to study the molecular pathology of axon
      degeneration, or myelin disorders, or of any peripheral neuropathy, also to study
      demyelination diseases in the central nervous system.

PMID- 29596859
TI  - On application of kernel PCA for generating stimulus features for fMRI during
      continuous music listening.
AB  - BACKGROUND: There has been growing interest towards naturalistic neuroimaging
      experiments, which deepen our understanding of how human brain processes and
      integrates incoming streams of multifaceted sensory information, as commonly
      occurs in real world. Music is a good example of such complex continuous
      phenomenon. In a few recent fMRI studies examining neural correlates of music in
      continuous listening settings, multiple perceptual attributes of music stimulus
      were represented by a set of high-level features, produced as the linear
      combination of the acoustic descriptors computationally extracted from the
      stimulus audio. NEW METHOD: fMRI data from naturalistic music listening
      experiment were employed here. Kernel principal component analysis (KPCA) was
      applied to acoustic descriptors extracted from the stimulus audio to generate a
      set of nonlinear stimulus features. Subsequently, perceptual and neural
      correlates of the generated high-level features were examined. RESULTS: The
      generated features captured musical percepts that were hidden from the linear PCA
      features, namely Rhythmic Complexity and Event Synchronicity. Neural correlates
      of the new features revealed activations associated to processing of complex
      rhythms, including auditory, motor, and frontal areas. COMPARISON WITH EXISTING
      METHOD: Results were compared with the findings in the previously published
      study, which analyzed the same fMRI data but applied linear PCA for generating
      stimulus features. To enable comparison of the results, methodology for finding
      stimulus-driven functional maps was adopted from the previous study. CONCLUSIONS:
      Exploiting nonlinear relationships among acoustic descriptors can lead to the
      novel high-level stimulus features, which can in turn reveal new brain structures
      involved in music processing.

PMID- 29596860
TI  - Endothelial dysfunction, endothelial nitric oxide bioavailability,
      tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease.
      Where are we with therapy?
AB  - Homeostasis around vascular endothelium is a function of the equilibrium between
      the bioavailability of nitric oxide (NO) and oxidizing reactive oxygen species
      (ROS). Within the vascular endothelium, NO enhances vasodilatation, reduces
      platelet aggression and adhesion (anti-thrombotic), prevents smooth muscle
      proliferation, inhibits adhesion of leukocytes and expression of pro-inflammatory
      cytokines genes (anti-inflammatory), and counters the oxidation of low density
      lipoprotein (LDL) cholesterol. A shift in the equilibrium that favours NO
      deficiency and ROS formation leads to endothelial dysfunction and cardiovascular
      disease. The synthesis of NO is catalysed by nitric oxide synthase and co
      factored by tetrahydrobiopterin (BH4), nicotinamide-adenine-dinucleotide
      phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide
      (FMN). The focus of this review is on endothelial nitric oxide synthase (eNOS),
      although we recognize that the other nitric oxide synthases may contribute as
      well. Levels of homocysteine and the active metabolite of folate, 5
      methyltetrahydrofolate (5-MTHF), play a determining role in circulating levels of
      nitric oxide. We review endothelial nitric oxide bioavailabilty in relation to
      endothelial dysfunction as well as the therapeutic strategies involving the
      nitric oxide synthesis pathway. Although folate supplementation improves
      endothelial function, results from large clinical trials and meta-analyses on
      palpable clinical endpoints have been inconsistent. There are however,
      encouraging results from animal and clinical studies of supplementation with the
      co-factor for nitric oxide synthesis, BH4, though its tendency to be oxidized to
      dihydrobiopterin (BH2) remains problematic. Understanding how to maintain a high
      ratio of BH4 to BH2 appears to be the key that will likely unlock the therapeutic
      potential of nitric oxide synthesis pathway.

PMID- 29596861
TI  - Numerical simulation of heat transfer in blood flow altered by electroosmosis
      through tapered micro-vessels.
AB  - A numerical simulation is presented to study the heat and flow characteristics of
      blood flow altered by electroosmosis through the tapered micro-vessels. Blood is
      assumed as non-Newtonian (micropolar) nanofluids. The flow regime is considered
      as asymmetric diverging (tapered) microchannel for more realistic micro-vessels
      which is produced by choosing the peristaltic wave train on the walls to have
      different amplitudes and phase. The Rosseland approximation is employed to model
      the radiation heat transfer and temperatures of the walls are presumed constants.
      The mathematical formulation of the present problem is simplified under the long
      wavelength, low-Reynolds number and Debye-Huckel linearization approximations.
      The influence of various dominant physical parameters are discussed for axial
      velocity, microrotation distribution, thermal temperature distribution and
      nanoparticle volume fraction field. However, our foremost emphasis is to
      determine the effects of thermal radiation and coupling number on the axial
      velocity and microrotation distribution beneath electroosmotic environment. This
      analysis places a significant observation on the thermal radiation and coupling
      number which plays an influential role in hearten fluid velocity. This study is
      encouraged by exploring the nanofluid-dynamics in peristaltic transport as
      symbolized by heat transport in biological flows and also in novel
      pharmacodynamics pumps and gastro-intestinal motility enhancement.

PMID- 29596862
TI  - Phosphoinositides and their functions in apicomplexan parasites.
AB  - Phosphoinositides are the phosphorylated derivatives of the structural membrane
      phospholipid phosphatidylinositol. Single or combined phosphorylation at the 3, 4
      and 5 positions of the inositol ring gives rise to the seven different species of
      phosphoinositides. All are quantitatively minor components of cellular membranes
      but have been shown to have important functions in multiple cellular processes.
      Here we describe our current knowledge of phosphoinositide metabolism and
      functions in apicomplexan parasites, mainly focusing on Toxoplasma gondii and
      Plasmodium spp. Even though our understanding is still rudimentary,
      phosphoinositides have already shown their importance in parasite biology and
      revealed some very particular and parasite-specific functions. Not surprisingly,
      there is a strong potential for phosphoinositide synthesis to be exploited for
      future anti-parasitic drug development.

PMID- 29596863
TI  - Analysis and prediction of presynaptic and postsynaptic neurotoxins by Chou's
      general pseudo amino acid composition and motif features.
AB  - Presynaptic neurotoxins and postsynaptic neurotoxins are two important
      neurotoxins isolated from venoms of venomous animals and have been proven to be
      potential effective in neurosciences and pharmacology. With the number of toxin
      sequences appeared in the public databases, there was a need for developing a
      computational method for fast and accurate identification and classification of
      the novel presynaptic neurotoxins and postsynaptic neurotoxins in the large
      databases. In this study, the Multinomial Naive Bayes Classifier (MNBC) had been
      developed to discriminate the presynaptic neurotoxins and postsynaptic
      neurotoxins based on the different kinds of features. The Minimum Redundancy
      Maximum Relevance (MRMR) feature selection method was used for ranking 400 pseudo
      amino acid (PseAA) compositions and 50 top ranked PseAA compositions were
      selected for improving the prediction results. The motif features, 400 PseAA
      compositions and 50 PseAA compositions were combined together, and selected as
      the input parameters of MNBC. The best correlation coefficient (CC) value of
      0.8213 was obtained when the prediction quality was evaluated by the jackknife
      test. It was anticipated that the algorithm presented in this study may become a
      useful tool for identification of presynaptic neurotoxin and postsynaptic
      neurotoxin sequences and may provide some useful help for in-depth investigation
      into the biological mechanism of presynaptic neurotoxins and postsynaptic
      neurotoxins.

PMID- 29596864
TI  - Effect of Low Androgen Status on the Expression of P2Y Receptors in the Corpus
      Cavernosum of Rats.
AB  - OBJECTIVE: To determine whether low androgen status impacts erectile function by
      regulating the expression of the G protein-coupled P2Y receptors (P2Y1, P2Y2,
      P2Y4, and P2Y6) in the corpus cavernosum penis of rats. MATERIALS AND METHODS: A
      total of 36 healthy, 8-week-old, male Sprague-Dawley rats were randomly allocated
      into 6 groups: 4 weeks of androgen replacement therapy post castration (group A);
      4 weeks post castration (group B); 4 weeks post sham operation (group C); 8 weeks
      of androgen replacement therapy post castration (group D); 8 weeks post
      castration (group E); and 8 weeks post sham operation (group F). The ratio of
      maximum intracavernous pressure/mean arterial pressure was measured for every
      group and detected the expression of P2Y1, P2Y2, P2Y4, and P2Y6 in the rat corpus
      cavernosum penis of every group. RESULTS: The ratio of maximum intracavernous
      pressure/mean arterial pressure significantly declined in the castration group
      compared with the control group (P <.01). The expression of P2Y1, P2Y2, P2Y4, and
      P2Y6 and the ratio of the phosphorylated endothelial nitric oxide synthase
      (eNOS)/eNOS proteins were significantly lower in the castration group vs
      treatment or control (P <.01) whereas they were significantly lower in the group
      of 8 weeks vs 4 weeks post castration (P <.05). The rat serum testosterone levels
      in every group were positively correlated with the protein levels of P2Y1, P2Y2,
      P2Y4, and P2Y6. CONCLUSION: Downregulation of the expression of the P2Y1, P2Y2,
      P2Y4, and P2Y6 receptors that reduces the ratio of phosphorylated eNOS/eNOS and
      eNOS activity may be one of the important mechanisms of erectile dysfunction
      caused by low androgen status.

PMID- 29596865
TI  - Filling a True Unmet Need: A New Therapy for Nonmetastatic Castrate-resistant
      Prostate Cancer Commentary on: Apalutamide Treatment and Metastasis-free Survival
      in Prostate Cancer.

PMID- 29596866
TI  - Preliminary Report on Stone Breakage and Lesion Size Produced by a New
      Extracorporeal Electrohydraulic (Sparker Array) Discharge Device.
AB  - OBJECTIVE: To determine if an innovative extracorporeal electrohydraulic shock
      wave (SW) device (sparker array [SPA]) can effectively fracture artificial stones
      in vitro and in vivo, and if SPA treatment produces a renal lesion in our pig
      model of lithotripsy injury. Results of these experiments will be used to help
      evaluate the suitability of this device as a clinical lithotripter. MATERIALS AND
      METHODS: Ultracal-30 artificial stones were placed in a holder at the focus of
      the SPA and treated with 600 SWs (21.6 kV, 60 shocks/min). Stone fragments were
      collected, dried, and weighed to determine stone breakage. In vivo stone breakage
      entailed implanting stones into pigs. These stones were treated with 600 or 1200
      SWs and the fragments were collected for analysis. Lesion analysis consisted of
      treating the left kidney of pigs with 1200 or 2400 SWs and quantitating the
      hemorrhagic lesion. RESULTS: In vitro, 71% +/- 2% of each artificial stone was
      fractured to <2 mm in size. In vivo stone breakage averaged 63%. Renal injury
      analysis revealed that only 1 of 7 kidneys showed evidence of hemorrhagic injury
      in the treated area. CONCLUSION: The SPA consistently comminuted artificial
      stones demonstrating its ability to fracture stones like other lithotripters.
      Also, the SPA caused little to no renal injury at the settings used in this
      study. These findings suggest further research is warranted to determine the
      potential of this device as a clinical lithotripter.

PMID- 29596868
TI  - Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding
      motifs.
AB  - We recently reported that in addition to its classical cytoplasmic location, the
      fast skeletal muscle Troponin T3 (TnT3) shuttles to the nucleus, where it appears
      to perform nonclassical transcription regulatory functions. Importantly, changes
      in the composition of the nucleus-localized pool of TnT3 and its fragments
      contribute to age-dependent muscle damage and wasting. Here, using ChIP-Seq, we
      demonstrate that TnT3 associates with DNA consensus sequences including the TGCCT
      motif, which is required for p53 binding to the promoter area of p53-related
      genes. Gene set enrichment analysis further demonstrated that the p53 pathway was
      the most significantly enriched pathway among genes annotated to the TnT3 ChIP
      Seq peaks. We further demonstrated a strong correlation (r = 0.78, P = 1 * 10-4)
      between the expression levels of TNNT3 and TP53-inducible ribonucleotide
      reductase regulatory subunit M2B (RRM2B) in skeletal muscle tissue of 21 lean non
      diabetic human subjects and a significant (P < 0.05) reduction in the levels of
      both gene transcripts in the third age-tertile group [42.3-70 years of age (yoa)]
      as compared to the second age-tertile (31.3-42.3 yoa). Of note, both TNNT3 and
      RRM2B expression levels negatively associated with total body fat mass (each with
      r = 0.49, P < 0.05), whereas RRM2B positively correlated with pancreatic beta
      cell function (rRRM2B~HOMA-B = 0.47, P = 0.047). This work suggests that reduced
      TNNT3 gene expression is another mechanism leading to reduced TnT3 and excitation
      contraction coupling with aging. Consequently, TnT3 appears to contribute to age
      related sarcopenia and possibly other age-related deficiencies such as muscle
      insulin resistance and beta cell dysfunction by interacting with TnT3-binding
      sequences in the promoter area of p53-related genes, among others, and
      consequently modulating the transcriptional regulation of these target genes.

PMID- 29596869
TI  - Retraining of automatic action tendencies in individuals with obesity: A
      randomized controlled trial.
AB  - Obesity is a major health concern, characterized by an automatically activated
      tendency to (over)-eat. Recent research suggests that an effective way to
      counteract automatic approach tendencies in unhealthy consumption behavior might
      be approach bias modification. Therefore, we investigated an approach-avoidance
      training for unhealthy food cues in 189 patients with obesity of a psychosomatic
      inpatient clinic who were participating in a nutrition advice program. Patients
      in the active training group were trained to make avoidance movements (pushing a
      joystick) in response to unhealthy food pictures and approach movements (pulling
      the joystick) in response to positive pictures, while the control group received
      sham training (approaching and avoiding both picture types). Approach-avoidance
      bias, body mass index, eating pathology and food-specific implicit associations
      were assessed before and after the training. In line with our hypothesis,
      approach-avoidance bias improved in the active training group after the training,
      in comparison to the sham training group. Moreover, this effect generalized to
      new, untrained stimuli. However, no effects of the training were found in a food
      specific Single-Target Implicit Association Test, or on eating pathology
      questionnaires or body mass index. While the training results are promising, the
      effect of approach-avoidance bias modification on relevant behavior in obesity
      has yet to be established before it may be implemented as an add-on treatment.

PMID- 29596870
TI  - A qualitative investigation of how mothers from low income households perceive
      their role during family meals.
AB  - BACKGROUND: Having regular family meals has been shown to be protective for child
      dietary intake (e.g., higher intake of fruit and vegetables). Mothers appear to
      be most responsible for preparing family meals. Therefore, understanding how
      mothers perceive their roles around family meals may help identify ways in which
      to help more families have regular family meals. METHODS: United States mothers
      (n = 83) from the Twin Cities, Minnesota were interviewed during an in-home
      visit. Researchers trained in qualitative interviewing used a semi-structured
      approach and asked questions regarding the mothers' overall perception of their
      role during family meals. Interviews were coded using a mixed deductive and
      inductive content analysis approach. The majority of mothers were from minority
      and low-income households. RESULTS: Mothers described their roles during family
      meals as the follows: 1) Helping children make healthy choices at family meals;
      2) Making the meal happen; 3) Monitoring children's food intake; 4) Managing
      behavior at the family meal; 5) Making the family meal atmosphere enjoyable; and
      6) Facilitating conversation/communication. Two secondary research questions also
      emerged about the specifics of the mothers' perception of her role at family
      meals (i.e., How do mothers deal with fighting or arguing if it occurs at family
      meals? and What do mothers talk about with children at family meals?)
      CONCLUSIONS: Results show that mothers have a large and varied role during family
      meals. Additionally, they are willing to put effort into family meals and want
      them to be enjoyable. Findings also suggest that mothers can be supported by
      encouraging fuller family participation in family meals and by offering mothers
      quality nutrition and parent feeding practice information.

PMID- 29596872
TI  - Caveolin-1 deficiency protects pancreatic beta cells against palmitate-induced
      dysfunction and apoptosis.
AB  - Lipotoxicity leads to insulin secretion deficiency, which is among the important
      causes for the onset of type 2 diabetes mellitus. Thus, the restoration of beta
      cell mass and preservation of its endocrine function are long-sought goals in
      diabetes research. Previous studies have suggested that the membrane protein
      caveolin-1 (Cav-1) is implicated in beta-cell apoptosis and insulin secretion,
      however, the underlying mechanisms still remains unclear. Our objective is to
      explore whether Cav-1 depletion protects pancreatic beta cells from lipotoxicity
      and what are the underlying mechanisms. In this study, we found that Cav-1
      silencing significantly promoted beta-cell proliferation, inhibited palmitate
      (PA)-induced pancreatic beta-cell apoptosis and enhanced insulin production and
      secretion. These effects were associated with enhanced activities of Akt and
      ERK1/2, which in turn downregulated the expression of cell cycle inhibitors
      (FOXO1, GSK3beta, P21, P27 and P53) and upregulated the expression of Cyclin D2
      and Cyclin D3. Subsequent inhibition of PI3K/Akt and ERK/MAPK pathways abolished
      Cav-1 depletion induced beta-cell mass protection. Furthermore, under PA induced
      endoplasmic reticulum (ER) stress, Cav-1 silencing significantly reduced
      eIF2alpha phosphorylation and the expression of ER stress-responsive markers BiP
      and CHOP, which are among the known sensitizers of lipotoxicity. Our findings
      suggest Cav-1 as potential target molecule in T2DM treatment via the preservation
      of lipotoxicity-induced beta-cell mass reduction and the attenuation of insulin
      secretion dysfunction.

PMID- 29596871
TI  - Heat shock protein 60 involvement in vascular smooth muscle cell proliferation.
AB  - AIM: Heat shock protein 60 (Hsp60) is a mediator of stress-induced vascular
      smooth muscle cell (VSMC) proliferation. This study will determine, first, if the
      mitochondrial or cytoplasmic localization of Hsp60 is critical to VSMC
      proliferation and, second, the mechanism of Hsp60 induction of VSMC proliferation
      with a focus on modification of nucleocytoplasmic trafficking. METHODS AND
      RESULTS: Hsp60 was overexpressed in primary rabbit VSMCs with or without a
      mitochondrial targeting sequence (AdHsp60mito-). Both interventions induced an
      increase in VSMC PCNA expression and proliferation. The increase in VSMC PCNA
      expression and growth was not observed after siRNA-mediated knockdown of Hsp60
      expression. Nuclear protein import in VSMC was measured by fluorescent microscopy
      using a microinjected fluorescent import substrate. Nuclear protein import was
      stimulated by both AdHsp60 and AdHsp60mito- treatments. AdHsp60 treatment also
      induced increases in nucleoporin (Nup) 62, Nup153, importin-alpha, importin-beta
      and Ran expression as well as cellular ATP levels compared to control.
      AdHsp60mito- treatment induced an up-regulation in importin-alpha, importin-beta
      and Ran expression compared to control. Hsp60 knockdown did not change nuclear
      protein import nor the expression of any nuclear transport receptors or
      nucleoporins. Both heat shock treatment and Hsp60 overexpression promoted the
      interaction of Ran with Hsp60. CONCLUSIONS: VSMC proliferation can be modulated
      via an Hsp60 dependent, cytosol localized mechanism that in part involves a
      stimulation of nuclear protein import through an interaction with Ran. This novel
      cellular signaling role for Hsp60 may be important in growth-based vascular
      pathologies like atherosclerosis and hypertension.

PMID- 29596867
TI  - The short-term stress response - Mother nature's mechanism for enhancing
      protection and performance under conditions of threat, challenge, and
      opportunity.
AB  - Our group has proposed that in contrast to chronic stress that can have harmful
      effects, the short-term (fight-or-flight) stress response (lasting for minutes to
      hours) is nature's fundamental survival mechanism that enhances protection and
      performance under conditions involving threat/challenge/opportunity. Short-term
      stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti
      tumor immune responses, and post-surgical recovery. Mechanisms and mediators
      include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte
      trafficking/function and local/systemic chemokine and cytokine production. Short
      term stress may also enhance mental/cognitive and physical performance through
      effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of
      threat/anxiety, and training-induced stress-optimization. Therefore, short-term
      stress psychology/physiology could be harnessed to enhance immuno-protection, as
      well as mental and physical performance. This review aims to provide a conceptual
      framework and targets for further investigation of mechanisms and conditions
      under which the protective/adaptive aspects of short-term stress/exercise can be
      optimized/harnessed, and for developing pharmacological/biobehavioral
      interventions to enhance health/healing, and mental/cognitive/physical
      performance.

PMID- 29596873
TI  - Highly efficacious and specific anti-glioma chemotherapy by tandem nanomicelles
      co-functionalized with brain tumor-targeting and cell-penetrating peptides.
AB  - Glioma is a highly challenging human malignancy as drugs typically exhibit a low
      blood-brain barrier (BBB) permeability as well as poor glioma selectivity and
      penetration. Here, we report that tandem nanomicelles co-functionalized with
      brain tumor-targeting and cell-penetrating peptides, Angiopep-2 and TAT, enable a
      highly efficacious and specific anti-glioma chemotherapy. Interestingly, tandem
      nanomicelles with 20 mol% Angiopep-2 and 10 mol% TAT linked via long and short
      poly(ethylene glycol)s, respectively, while maintaining a high glioma cell
      selectivity display markedly enhanced BBB permeation, glioma accumulation and
      penetration, and glioma cell uptake. We further show that docetaxel-loaded tandem
      nanomicelles have a long blood circulation time in mice and significantly better
      inhibit orthotopic U87MG human glioma than the corresponding Angiopep-2 single
      peptide-functionalized control, leading to an improved survival rate with little
      adverse effects. These tandem nanomicelles uniquely combining brain tumor
      targeting and cell-penetrating functions provide a novel and effective strategy
      for targeted glioma therapy.

PMID- 29596874
TI  - Controlling release from 3D printed medical devices using CLIP and drug-loaded
      liquid resins.
AB  - Mass customization along with the ability to generate designs using medical
      imaging data makes 3D printing an attractive method for the fabrication of
      patient-tailored drug and medical devices. Herein we describe the application of
      Continuous Liquid Interface Production (CLIP) as a method to fabricate
      biocompatible and drug-loaded devices with controlled release properties, using
      liquid resins containing active pharmaceutical ingredients (API). In this work,
      we characterize how the release kinetics of a model small molecule, rhodamine B
      base (RhB), are affected by device geometry, network crosslink density, and the
      polymer composition of polycaprolactone- and poly (ethylene glycol)-based
      networks. To demonstrate the applicability of using API-loaded liquid resins with
      CLIP, the UV stability was evaluated for a panel of clinically-relevant small
      molecule drugs. Finally, select formulations were tested for biocompatibility,
      degradation and encapsulation of docetaxel (DTXL) and dexamethasone-acetate
      (DexAc). Formulations were shown to be biocompatible over the course of 175 days
      of in vitro degradation and the clinically-relevant drugs could be encapsulated
      and released in a controlled fashion. This study reveals the potential of the
      CLIP manufacturing platform to serve as a method for the fabrication of patient
      specific medical and drug-delivery devices for personalized medicine.

PMID- 29596875
TI  - Reply to: "Cutaneous squamous cell carcinoma progression during imiquimod
      treatment".

PMID- 29596876
TI  - Successful treatment of severe psoriasis relapse with secukinumab (interleukin 17
      A inhibitor) after abrupt brodalumab (interleukin 17 receptor inhibitor)
      discontinuation: A retrospective study evaluating long-term efficacy and safety.

PMID- 29596877
TI  - Reply to Joseph et al.

PMID- 29596878
TI  - Authors' reply.

PMID- 29596879
TI  - A novel bacterial symbiont association in the hispid beetle, Octodonta nipae
      (Coleoptera: Chrysomelidae), their dynamics and phylogeny.
AB  - The hispid leaf beetle, Octodonta nipae (Maulik), (Coleoptera: Chrysomelidae), is
      a devastating pest of palm cultivation worldwide. Endosymbiotic bacteria in the
      genus Wolbachia are arguably one of the most abundant bacterial group associated
      with arthropods. Owing to its critical effects on host reproduction, Wolbachia
      has garnered much attention as a prospective future tool for insect pest
      management. However, their association, infection dynamics, and functionality
      remain unknown in this insect pest. Here, we diagnosis for the first time, the
      infection prevalence, and occurrence of Wolbachia in O. nipae. Experimental
      evidence by the exploration of wsp gene vindicate that O. nipae is naturally
      infected with bacterial symbiont of genus Wolbachia, showing a complete maternal
      inheritance with shared a common Wolbachia strain (wNip). Moreover, MLST (gatB,
      fbpA, coxA, ftsZ, and hcpA) analysis enabled the detections of new sequence type
      (ST-484), suggesting a particular genotypic association of O. nipae and
      Wolbachia. Subsequently, quantitative real-time PCR (qPCR) assay demonstrated
      variable infection density across different life stages (eggs, larvae, pupae and
      adult male and female), body parts (head, thorax, abdomen), and tissues (ovaries,
      testes, and guts). Infection density was higher in egg and female adult stage, as
      well as abdomen and reproductive tissues as compared to other samples.
      Interestingly, Wolbachia harbored dominantly in a female than the male adult,
      while, no significant differences were observed between male and female body
      parts and tissues. Phylogeny of Wolbachia infection associated with O. nipae
      rectified from all tested life stages were unique and fall within the same
      monophyletic supergroup-A of Wolbachia clades. The infection density of symbiont
      is among the valuable tool to understand their biological influence on hosts, and
      this latest discovery would facilitate the future investigations to understand
      the host-symbiont complications and its prospective role as a microbiological
      agent to reduce pest populations.

PMID- 29596880
TI  - Evaluation of antibacterial and antioxidant potential of the zinc oxide
      nanoparticles synthesized by aqueous and polyol method.
AB  - In this paper, we have reported the synthesis, characterization, and evaluation
      of antimicrobial and antioxidant potential of monodispersed Zinc Oxide (ZnO)
      nanoparticles synthesized by the room temperature precipitation (aqueous phase)
      and polyol method (organic phase). ZnO nanoparticle synthesized by both the
      methods had shown excellent DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical
      scavenging, metal chelating (MC), ABTS (2,2'-azino-bis; 3-ethylbenzothiazoline-6
      sulphonic acid), hydroxyl radical and superoxide radical scavenging activity
      (SAS). Scavenging activities were assayed within a concentration range of 25-75
      ng ml-1. The antibacterial activities with MIC were investigated against two Gram
      positive bacteria Streptococcus mutans (MTCC 497) and S. pyogens (MTCC 1926);
      three Gram negative bacteria Vibrio cholerae (MTCC 3906), Shigella flexneri (MTCC
      1457) and Salmonella typhii (MTCC 1252). ZnO nanoparticles synthesized by the
      polyol method showed better MIC values against both Gram-positive and Gram
      negative bacteria as compared to particles synthesized by aqueous precipitation
      method. Present study demonstrates the successful synthesis of ZnO nanoparticles
      with antioxidant property and significant broad spectrum antibacterial activity
      against several clinical bacterial pathogens.

PMID- 29596881
TI  - NMR structures in different membrane environments of three ocellatin peptides
      isolated from Leptodactylus labyrinthicus.
AB  - The peptides ocellatin-LB1, -LB2 and -F1 have previously been isolated from
      anurans of the Leptodactylus genus and the sequences are identical from residue 1
      22, which correspond to ocellatin-LB1 sequence (GVVDILKGAAKDIAGHLASKVM-NH2),
      whereas ocellatin-LB2 carries an extra N and ocellatin-F1 extra NKL residues at
      their C-termini. These peptides showed different spectra of activities and
      biophysical investigations indicated a direct correlation between membrane
      disruptive properties and antimicrobial activities, i.e. ocellatin-F1 > ocellatin
      LB1 > ocellatin-LB2. To better characterize their membrane interactions, we
      report here the detailed three-dimensional NMR structures of these peptides in
      TFE-d2:H2O (60:40) and in the presence of zwitterionic DPC-d38 and anionic SDS
      d25 micellar solutions. Although the three peptides showed significant helical
      contents in the three mimetic environments, structural differences were noticed.
      When the structures of the three peptides in the presence of DPC-d38 micelles are
      compared to each other, a more pronounced curvature is observed for ocellatin-F1
      and the bent helix, with the concave face composed mostly of hydrophobic
      residues, is consistent with the micellar curvature and the amphipathic nature of
      the molecule. Interestingly, an almost linear helical segment was observed for
      ocellatin-F1 in the presence of SDS-d25 micelles and the conformational
      differences in the two micellar environments are possibly related to the presence
      of the extra Lys residue near the peptide C-terminus, which increases the
      affinity of ocellatin-F1 to anionic membranes in comparison with ocellatin-LB1
      and -LB2, as proved by isothermal titration calorimetry. To our knowledge, this
      work reports for the first time the three-dimensional structures of ocellatin
      peptides.

PMID- 29596882
TI  - SWI/SNF subunit expression heterogeneity in human aplastic anemia
      stem/progenitors.
AB  - Acquired aplastic anemia (AA) is a bone marrow (BM) failure associated with
      autoimmune destruction of hematopoietic stem cells (HSCs). Although somatic
      mutations have been identified in AA patients, mutations alone do not explain AA
      pathophysiology. SWI/SNF is an evolutionarily conserved, multi-subunit, ATP
      dependent chromatin-remodeling protein complex that plays an important role in
      mammalian hematopoiesis. Herein, gene expression analysis identified a
      significant loss of the SWI/SNF core component SMARCC1, along with ARID1B,
      ACTL6A, and SMARCD1, in human AA BM CD34+ HSCs and hematopoietic stem and
      progenitor cells (HSPCs) compared with normal HSPCs. However, expression of
      SMARCA4, SMARCB1, SMARCD3, and DPF2 remained intact in our AA cohort. PBRM1,
      BRD7, and SMARCA2 expression were significantly upregulated in both untreated and
      follow-up AA patients. Clonal hematopoiesis in AA is associated with evolution to
      late clonal disorders, including myelodysplastic syndromes (MDS). Apart from
      SMARCD1 loss, we did not observe significant alteration of SWI/SNF expression in
      MDS HSPCs, indicating SWI/SNF differential expression in AA and MDS. In addition,
      except for ACTL6A, SWI/SNF expression was unaltered in aged HSPCs. Importantly,
      our results provide evidence for loss of SWI/SNF in AA, and may implicate AA HSPC
      autonomous defective SWI/SNF regulation as an integral component of BM failure,
      in addition to autoimmune destruction of AA HSCs. These findings illustrate for
      the first time SWI/SNF subunit expression heterogeneity in human AA HSPCs and
      require prognostic validation in a larger cohort.

PMID- 29596883
TI  - Antagonistic activities of miR-148a and DNMT1: Ectopic expression of miR-148a
      impairs DNMT1 mRNA and dwindle cell proliferation and survival.
AB  - Functional analyses of noncoding RNAs have associated many micro RNAs (miRNA,
      miR) with various physiological processes, including proliferation,
      differentiation, development, cell metabolism, and apoptosis. Aberrant expression
      of miRNA and imbalance in their functions may lead to cellular aberration and
      different disease development, including cancer. In silico analysis of miRNA
      target prediction suggested that miR-148a possess a binding site in the 3' UTR of
      DNMT1 mRNA which can cause silencing of DNMT1 gene. Accordingly, we performed in
      vitro cell culture experiments to confirm the effect miR-148a on DNMT1 gene
      expression in prostate cancer cell lines. We demonstrated that there is a
      physical association between DNMT1 mRNA and miR-148a. We found that (i) ectopic
      expression of miR-148a induces programmed cell death and represses cell
      proliferation by targeting DNMT1; (ii) miR-148a gene is regulated by DNA
      methylation and DNMT1 in prostate cancer. We conclude that miR-148a is silenced
      by DNA methylation and ectopic expression of miR-148a suppresses DNMT1 expression
      and induced apoptotic genes expression in hormone-refractory prostate cancer
      cells.

PMID- 29596885
TI  - Significance of the mitochondrial thioredoxin reductase in cancer cells: An
      update on role, targets and inhibitors.
AB  - Thioredoxin reductase 2 (TrxR2) is a key component of the mitochondrial
      thioredoxin system able to transfer electrons to peroxiredoxin 3 (Prx3) in a
      reaction mediated by thioredoxin 2 (Trx2). In this way, both the level of
      hydrogen peroxide and thiol redox state are modulated. TrxR2 is often
      overexpressed in cancer cells conferring apoptosis resistance. Due to their
      exposed flexible arm containing selenocysteine, both cytosolic and mitochondrial
      TrxRs are inhibited by a large number of molecules. The various classes of
      inhibitors are listed and the molecules acting specifically on TrxR2 are
      extensively described. Particular emphasis is given to gold(I/III) complexes with
      phosphine, carbene or other ligands and to tamoxifen-like metallocifens. Also
      chemically unrelated organic molecules, including natural compounds and their
      derivatives, are taken into account. An important feature of many TrxR2
      inhibitors is provided by their nature of delocalized lipophilic cations that
      allows their accumulation in mitochondria exploiting the organelle membrane
      potential. The consequences of TrxR2 inhibition are presented focusing especially
      on the impact on mitochondrial pathophysiology. Inhibition of TrxR2, by hindering
      the activity of Trx2 and Prx3, increases the mitochondrial concentration of
      reactive oxygen species and shifts the thiol redox state toward a more oxidized
      condition. This is reflected by alterations of specific targets involved in the
      release of pro-apoptotic factors such as cyclophilin D which acts as a regulator
      of the mitochondrial permeability transition pore. Therefore, the selective
      inhibition of TrxR2 could be utilized to induce cancer cell apoptosis.

PMID- 29596884
TI  - STIP1 is over-expressed in hepatocellular carcinoma and promotes the growth and
      migration of cancer cells.
AB  - Wnt/beta-catenin signaling is frequently activated in hepatocellular carcinoma
      (HCC). Better understanding the mechanism for its over-activation would help the
      therapy. In this study, we have shown that the stress-induced phosphoprotein 1
      (STIP1) is up-regulated in the HCC tissues. Functional studies showed that STIP1
      promoted the growth, colony formation and migration of cancer cells. However,
      knocking down the expression of STIP1 inhibited the growth, colony formation and
      migration of cancer cells. Molecular mechanism study showed that STIP1 interacted
      with Axin, enhanced the interaction between Axin and DVL2, thus activated beta
      catenin/TCF signaling. Taken together, our study demonstrated the oncogenic roles
      of STIP1 in the progression of HCC, and suggested that STIP1 might be a
      therapeutic target.

PMID- 29596886
TI  - Environmental and occupational exposure to resorcinol in Finland.
AB  - Resorcinol is a suspected endocrine disruptor that affects thyroid function by
      inhibiting thyroxin peroxidase. It may also have an impact on iodine uptake.
      Resorcinol has various uses; for example in the manufacture of rubber products
      and in wood adhesives, flame retardants, UV stabilizers, and dyes. It is also
      used in personal care products such as hair colorants, anti-acne preparations,
      and peels. The aim of this study was to assess both environmental background
      exposure and occupational exposure to resorcinol in Finland. We investigated
      occupational exposure in hairdresser work and in the manufacture of tyres,
      adhesive resins and glue-laminated timber by biomonitoring total resorcinol
      concentration in urine samples. The biomonitoring results were compared to the
      urinary levels of occupationally non-exposed volunteers, and to the biomonitoring
      equivalent (BE), which we estimated on the basis of the EFSA's acceptable daily
      intake (ADI) value for resorcinol. Almost all the urine samples (99%) of the non
      occupationally exposed volunteers contained measurable amounts of resorcinol. The
      urinary resorcinol data were rather scattered, and the resorcinol concentrations
      among women (GM 84 MUg/l, 95th percentile 2072 MUg/l) were clearly higher than
      the respective concentrations among men (GM 35 MUg/l, 95th percentile 587 MUg/l).
      The reason for this difference remains unclear. Although the two highest results
      exceeded the BE of 4 mg/l calculated on the basis of the EFSA's ADI, the 95th
      percentile of the occupationally non-exposed volunteers' results remained well
      below the BE among both males and females. According to the results,
      hairdressers' exposure to resorcinol was at the same level as that of the
      reference population of occupationally non-exposed volunteers. All hairdresser's
      values remained below the BE for resorcinol. The urinary resorcinol levels of the
      industrial workers were also at the same level as those of the reference
      population. We observed slight increases in the post-shift and evening samples of
      those working in the manufacture of tyres and adhesive resins. The results of
      some workers in the tyre manufacturing company exceeded the 95th percentile of
      non-occupationally exposed males, which was used as a biological guidance value
      for occupational exposure. Moreover, in this case exposure was below the health
      based biomonitoring equivalents. All the air samples collected in the companies
      contained very low resorcinol concentrations. It should be noted that the sample
      sizes for the male controls and industrial groups were small.

PMID- 29596888
TI  - Squalene epoxidase as a promising metabolic target in cancer treatment.
AB  - Oncogenic alteration of the cholesterol synthesis pathway is a recognized
      mechanism of metabolic adaptation. In the present review, we focus on squalene
      epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis,
      retracing its history since its discovery as an antimycotic target to its
      description as an emerging metabolic oncogene by amplification with clinical
      relevance in cancer. We review the published literature assessing the association
      between SE over-expression and poor prognosis in this disease. We assess the
      works demonstrating how SE promotes tumor cell proliferation and migration, and
      displaying evidence of cancer cell demise in presence of human SE inhibitors in
      in vitro and in vivo models. Taken together, robust scientific evidence has by
      now accumulated pointing out SE as a promising novel therapeutic target in cancer
      treatment.

PMID- 29596887
TI  - Derivation of an inhalation TTC for the workplace based on DNEL values reported
      under REACH.
AB  - The Threshold of Toxicological Concern (TTC) concept defines a generic tolerable
      exposure for chemicals of unknown toxicity below which the risk of adverse health
      effects is considered very small. The original concept was refined and extended
      over the years, based either on differentiated structural classes or on
      additional information on certain toxicological endpoints. Initially, the focus
      of the TTC application was only on systemic toxic effects after repeated oral
      intake and consisted of one value. However, under well-defined boundary
      conditions, a long-term systemic inhalation TTC could also serve as a cut-off
      criterion for occupational exposure in those cases where workers are exposed to
      very low levels of chemicals by inhalation contact and could therefore reduce the
      need to perform animal tests. Within the scope of the European REACH legislation,
      several thousand systemic long-term inhalation Derived No Effect Levels (DNELs)
      for workers have been published. By statistical evaluation of the DNEL
      distribution of 1876 chemicals and the resulting 99th percentiles, we propose an
      inhalation workplace TTC for systemic effects in the region of 50 MUg/m3 (7
      MUg/kg body weight/day). Specific exclusion criteria apply for the discussed
      concept.

PMID- 29596889
TI  - Pro-apoptotic Bax promotes mesenchymal-epithelial transition by binding to
      respiratory complex-I and antagonizing the malignant actions of pro-survival Bcl
      2 proteins.
AB  - The plasticity of solid tumors between the epithelial and mesenchymal states
      critically influences their malignant progression and metastasis. The epithelial
      mesenchymal transition (EMT), which supports cancer cell invasion and metastasis,
      is promoted by pro-survival members (e.g., Bcl-2 and Bcl-XL) of the Bcl-2 protein
      family, which are well-known key apoptosis regulators. We found that Bcl-w,
      another pro-survival member, promotes EMT by increasing respiratory complex-I
      activity and reactive oxygen species (ROS) levels. In contrast, pro-apoptotic Bax
      facilitates mesenchymal-epithelial transition by binding to complex-I, which
      inhibits complex-I-induced ROS production. Functional antagonism between pro
      survival and pro-apoptotic proteins in regulating tumor plasticity was directly
      confirmed by co-expressing Bax with Bcl-w or Bcl-XL. Therefore, the balance
      between the functionally opposing Bcl-2 proteins appears to be a critical
      determinant of cancer cell phenotypes. We further showed that sub-lethal doses of
      gamma-radiation induced EMT by increasing Bcl-XL and Bcl-w levels and complex-I
      activity. We propose that Bcl-2 proteins and complex-I are potential targets for
      preventing tumor progression and the malignant actions of radiotherapy.

PMID- 29596890
TI  - Immuno-modulators enhance antigen-specific immunity and anti-tumor effects of
      mesothelin-specific chimeric DNA vaccine through promoting DC maturation.
AB  - As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies.
      MSLN is potential for antigen-specific cancer vaccines. We generated a novel
      chimeric DNA vaccine using antigen-specific connective tissue growth factor lined
      with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine
      combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were
      validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and
      poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer
      survival and less tumor volumes. An increase in MSLN-specific CD8+ T cells and
      anti-MSLN Ab titers was also noted in CTGF/MSLN DNA with anti-CD40Ab and
      poly(I:C) vaccinated mice. The CTGF/MSLN DNA vaccine combined with immuno
      modulator EGCG also generated potent anti-tumor effects. Immuno-modulators could
      enhance the antigen-specific anti-tumor effects of CTGF/MSLN DNA vaccine through
      promoting the DC maturation. In addition, MSLN-specific cell-based vaccine with
      AAV-IL-12 and the CTGF/MSLN DNA vaccine with anti-CD40Ab/polyp(I:C) generated
      more potent anti-tumor effects than the other combinational regimens. The results
      indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be
      an effective immunotherapeutic strategy to control MSLN-expressing tumors
      including ovarian and pancreastic cancers, and malignant mesothelioma.

PMID- 29596891
TI  - Connexin 43 regulates the expression of wound healing-related genes in human
      gingival and skin fibroblasts.
AB  - Fibroblasts are the most abundant connective tissue cells and play an important
      role in wound healing. It is possible that faster and scarless wound healing in
      oral mucosal gingiva relative to skin may relate to the distinct phenotype of the
      fibroblasts residing in these tissues. Connexin 43 (Cx43) is the most ubiquitous
      Cx in skin (SFBLs) and gingival fibroblasts (GFBLs), and assembles into
      hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We hypothesized
      that SFBLs and GFBLs display distinct expression or function of Cx43, and that
      this may partly underlie the different wound healing outcomes in skin and
      gingiva. Here we show that Cx43 distinctly formed Cx43 GJs and HCs in human skin
      and gingiva in vivo. However, in SFBLs, in contrast to GFBLs, only a small
      proportion of total Cx43 assembled into HC plaques. Using an in vivo-like 3D
      culture model, we further show that the GJ, HC, and channel-independent functions
      of Cx43 distinctly regulated wound healing-related gene expression in GFBLs and
      SFBLs. Therefore, the distinct wound healing outcomes in skin and gingiva may
      partly relate to the inherently different assembly and function of Cx43 in the
      resident fibroblasts.

PMID- 29596892
TI  - Dysfunction of cholesterol sensor SCAP promotes inflammation activation in THP-1
      macrophages.
AB  - Crosstalk occurs between dyslipidemia and chronic inflammation, which are both
      precipitants of atherosclerosis. Sterol regulatory element binding proteins
      cleavage-activating protein (SCAP) plays a key role in regulating cholesterol
      homeostasis. The present study investigated the effects of SCAP dysfunction on
      the expression of inflammatory cytokines and lipid metabolism in THP-1
      macrophages. Intracellular cholesterol content was assessed by Oil Red O staining
      and quantitative assays. The expression of SCAP, HMGCR, pro-IL-1beta and N
      SREBP2, p65(N) in the nucleus were examined by real-time quantitative RT-PCR and
      Western blotting. The level of secretary proteins IL-1beta, TNF-alpha and MCP-1
      in the supernatants were determined by ELISA. The translocation of SCAP from the
      endoplasmic reticulum (ER) to the Golgi was detected by confocal microscopy. Our
      results demonstrated that over-expression of SCAP significantly increased the
      expression of HMGCR, pro-IL-1beta in the cytoplasm, and mature IL-1beta, TNF
      alpha, MCP-1 in the supernatants, while knocking down SCAP dramatically decreased
      the expression of these molecules. Betulin effectively suppressed the
      accumulation of intracellular cholesterol in the SCAP over-expressed THP-1
      macrophages, but did not affect the expression of inflammatory cytokines,
      indicating that the pro-inflammatory effect of SCAP was independent of its
      routine role in regulating cholesterol homeostasis. Furthermore, we investigated
      the molecular mechanisms mediating the crosstalk between dyslipidemia and
      inflammatory responses. Knocking down SCAP attenuated LPS-induced IkappaB
      phosphorylation and reduced the nuclear level of p65, while over-expression of
      SCAP increased the nuclear level of p65. Knocking down p65 abolished the
      proinflammatory effect represented by elevated expression of the inflammatory
      mediators in the SCAP over-expressed THP-1 macrophages, suggesting that SCAP
      dysfunction stimulated inflammatory responses via activating the NF-kappaB
      signaling pathway. In conclusion, the cholesterol sensor SCAP plays a role in
      regulating the expression of inflammatory factors such as IL-1beta, TNF-alpha,
      and MCP-1 in THP-1 macrophages. SCAP mediates the inflammatory response via
      activating the NF-kappaB pathway. This new function of SCAP is independent of its
      role in lipid metabolism.

PMID- 29596893
TI  - Tumor microenvironment in functional adrenocortical adenomas: immune cell
      infiltration in cortisol-producing adrenocortical adenoma.
AB  - The tumor microenvironment plays pivotal roles in various human neoplasms.
      However, that of benign tumor, particularly hormone-secreting endocrine tumors,
      has remained virtually unknown. Therefore, we firstly attempted to analyze the
      tumor microenvironment of autonomous hormone-secreting adrenocortical adenomas.
      We first histologically evaluated 21 cortisol-producing adrenocortical adenoma
      (CPA) and 13 aldosterone-producing adrenocortical adenoma (APA) cases.
      Quantitative histologic analysis revealed that intratumoral immune cell
      infiltration (ICI) was more pronounced in CPAs than in APAs. We then evaluated
      the cytokine and chemokine profiles using polymerase chain reaction arrays in
      APAs and CPAs. Angiogenic chemokines, C-X-C motif chemokine ligand (CXCL) 1 and
      CXCL2, were significantly more abundant in CPAs than in APAs using subsequent
      quantitative polymerase chain reaction and immunohistochemical analyses. We then
      examined the vascular density between these 2 adenomas, and the density was
      significantly higher in overt CPAs than in APAs. Of particular interest, CXCL12
      positive vessels were detected predominantly in CPAs, and their infiltrating
      immune cells were C-X-C motif chemokine receptor 4 (CXCR4) positive. These
      results above indicated that CXCL12-CXCR4 signaling could partly account for ICI
      detected predominantly in CPAs. We then further explored the etiology of ICI in
      CPAs by evaluating the senescence of tumor cells possibly caused by excessive
      cortisol in CPAs. The status of senescence markers, p16 and p21, was
      significantly more abundant in CPAs than in APAs. In addition, all CPA cases
      examined were positive for senescence-associated beta-galactosidase. These
      results all indicated that exposure to local excessive cortisol could result in
      senescence of tumors cells and play essential roles in constituting the
      characteristic tissue microenvironment of CPAs.

PMID- 29596894
TI  - Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal
      adenocarcinomas than to neuroendocrine tumors G3.
AB  - Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring
      TP53 and RB1 alterations and lacking neuroendocrine-related genetic changes such
      as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile
      with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a
      detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell
      (n = 9) and small cell type (n = 3) using massive parallel sequencing applying a
      409-gene panel on an Ion Torrent system. The genetic data were compared with
      known data of pancreatic ductal adenocarcinoma and correlated with exocrine
      lineage marker expression. A similar analysis was performed in 11 pancreatic
      neuroendocrine tumors G3. Neuroendocrine carcinomas harbored 63 somatic mutations
      in 45 different genes, affecting most commonly TP53 (8/12 cases), KRAS (5/12
      cases), and RB1 (loss of expression with or without deletion in 4/12 cases). Five
      carcinomas had both TP53 and KRAS mutations. Neuroendocrine tumors G3 only shared
      singular mutations in 5 different genes with neuroendocrine carcinomas, including
      TP53, CDKN2A, ARID1A, LRP1B, and APC, affecting 5 different cases. Most KRAS
      positive neuroendocrine carcinomas also expressed MUC1 (4/5) and carcinoembryonic
      antigen (3/5) as markers of ductal differentiation. Our data indicate that almost
      half of the pancreatic neuroendocrine carcinomas are genetically and
      phenotypically related to pancreatic ductal adenocarcinoma, and might therefore
      respond to chemotherapies targeting the latter carcinomas.

PMID- 29596895
TI  - Microscopic ileitis in diverted and nondiverted enteric segments: an
      underrecognized condition with a multifactorial etiology.
AB  - Microscopic ileitis has been infrequently reported in the literature with the few
      reported cases usually associated with concurrent microscopic colitis. Having
      encountered a case of collagenous ileitis involving the diverted distal limb of a
      loop ileostomy and sparing the proximal limb, we examined additional cases of
      loop ileostomy, end ileostomy, colostomy, and the accompanying diverted
      colorectal segment for features of microscopic ileitis and colitis. A total of
      101 cases of diverted and nondiverted enteric segments were examined from 37 loop
      ileostomies, 16 end ileostomies, and 12 colostomies status post-Hartmann's
      procedure. The patients' clinical histories, including demographics and risk
      factors for microscopic colitis, were obtained from electronic medical records.
      The index case and an additional case showed collagenous ileitis: the former in
      the diverted distal limb, and the latter in the nondiverted proximal limb of the
      loop ileostomy. The latter was associated with high ileostomy output with watery
      diarrhea. Two additional cases showed lymphocytic ileitis: one in the nondiverted
      proximal limb of loop ileostomy and the other in the end ileostomy. All 4
      patients had one or more risk factors for microscopic colitis. The etiology of
      microscopic ileitis seems to be multifactorial, and microscopic ileitis may be
      underdiagnosed. The diverted enteric segment may be involved by microscopic
      enteritis, suggesting that additional factors other than fecal stasis and altered
      bacterial flora may be contributing to its pathogenesis. When microscopic ileitis
      is encountered, identifying associated risk factors, recognizing incipient
      clinical symptoms of microscopic colitis, and considering other associated
      diseases or conditions are warranted.

PMID- 29596896
TI  - Minute mesenchymal chondrosarcoma within osteochondroma: an unexpected diagnosis
      confirmed by HEY1-NCOA2 fusion.
AB  - Mesenchymal chondrosarcoma is rare and can be challenging to diagnose. Herein, we
      report a minute mesenchymal chondrosarcoma within an osteochondroma. A 12-year
      old girl presented with an asymptomatic exophytic lesion of the rib. The tumor
      was clinically diagnosed as osteochondroma and was excised after observation for
      3 years. The resected specimen revealed an unexpected minute (0.9 cm)
      "monophasic" mesenchymal chondrosarcoma in the apex of the lesion. The sarcoma
      consisted of monomorphic spindle cells without hyaline cartilage. Fluorescence in
      situ hybridization detected NCOA2 rearrangement, and reverse-transcription
      polymerase chain reaction and sequencing detected a HEY1 (exon 4)-NCOA2 (exon 13)
      fusion transcript. The patient did not receive adjuvant therapy and is alive with
      no recurrence 6 years after surgery. The present case highlights the value of
      careful pathological examination of specimens submitted as osteochondroma and
      emphasizes the usefulness of molecular assays in the diagnosis of mesenchymal
      chondrosarcoma in an atypical setting.

PMID- 29596898
TI  - Histamine-deficient mice do not respond to the antidepressant-like effects of
      oleoylethanolamide.
AB  - It has been suggested that the bioactive lipid mediator oleoylethanolamide (OEA),
      a potent agonist of the peroxisome proliferator-activated receptor-alpha (PPAR
      alpha) possesses anti-depressant-like effects in several preclinical models. We
      recently demonstrated that several of OEA's behavioural actions require the
      integrity of the brain histaminergic system, and that an intact histaminergic
      neurotransmission is specifically required for selective serotonin re-uptake
      inhibitors to exert their anti-depressant-like effect. The purpose of our study
      was to test if OEA requires the integrity of the histaminergic neurotransmission
      to exert its antidepressant-like effects. Immobility time in the tail suspension
      test was measured to assess OEA's potential (10 mg/kg i.p.) as an antidepressant
      drug in histidine decarboxylase null (HDC-/-) mice and HDC+/+ littermates, as
      well as in PPAR-alpha+/+ and PPAR-alpha-/- mice. CREB phosphorylation was
      evaluated using Western blot analysis in hippocampal and cortical homogenates, as
      pCREB is considered partially responsible for the efficacy of antidepressants.
      Serotonin release from ventral hippocampi of HDC+/+ and HDC-/- mice was measured
      with in-vivo microdialysis, following OEA administration. OEA decreased
      immobility time and increased brain pCREB levels in HDC+/+ mice, whereas it was
      ineffective in HDC-/- mice. Comparable results were obtained in PPAR-alpha+/+ and
      PPAR-alpha-/- mice. Microdialysis revealed a dysregulation of serotonin release
      induced by OEA in HDC-/- mice. Our observations corroborate our hypothesis that
      brain histamine and signals transmitted by OEA interact to elaborate appropriate
      behaviours and may be the basis for the efficacy of OEA as an antidepressant-like
      compound.

PMID- 29596897
TI  - Mechanisms of neurotrophin trafficking via Trk receptors.
AB  - In neurons, long-distance communication between axon terminals and cell bodies is
      a critical determinant in establishing and maintaining neural circuits.
      Neurotrophins are soluble factors secreted by post-synaptic target tissues that
      retrogradely control axon and dendrite growth, survival, and synaptogenesis of
      innervating neurons. Neurotrophins bind Trk receptor tyrosine kinases in axon
      terminals to promote endocytosis of ligand-bound phosphorylated receptors into
      signaling endosomes. Trk-harboring endosomes function locally in axons to acutely
      promote growth events, and can also be retrogradely transported long-distances to
      remote cell bodies and dendrites to stimulate cytoplasmic and transcriptional
      signaling necessary for neuron survival, morphogenesis, and maturation. Neuronal
      responsiveness to target-derived neurotrophins also requires the precise axonal
      targeting of newly synthesized Trk receptors. Recent studies suggest that
      anterograde delivery of Trk receptors is regulated by retrograde neurotrophin
      signaling. In this review, we summarize current knowledge on the functions and
      mechanisms of retrograde trafficking of Trk signaling endosomes, and highlight
      recent discoveries on the forward trafficking of nascent receptors.

PMID- 29596899
TI  - Proteomic characterization of hippocampus of chronically socially isolated rats
      treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of
      action.
AB  - Due to the severity of depressive symptoms, there remains a necessity in defining
      the underlying mechanisms of depression and the precise actions of
      antidepressants in alleviating these symptoms. Proteomics is a powerful and
      promising tool for discovering novel pathways of cellular responses to disease
      and treatment. As chronic social isolation (CSIS) is a valuable animal model for
      studying depression, we performed a comparative subproteomic study of rat
      hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect
      of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day).
      Behaviorally, Flx treatment normalized the decreased sucrose preference and
      increased marble burying results resulting from CSIS, indicative of a FLX-induced
      attenuation of both anhedonia and anxiety. An analysis of cytosolic and
      nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in
      down-regulation of proteins involved in mitochondrial transport and energy
      processes, primarily tricarboxylic acid (TCA) cycle and oxidative
      phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS
      altered proteins and additional expression of other transporter and energy
      involved proteins. Immunohistochemical analysis revealed hippocampal subregion
      specific effects of CSIS and/or Flx treatment on selective protein expressions.

PMID- 29596900
TI  - Role of nitric oxide and WNK-SPAK/OSR1-KCC2 signaling in daily changes in
      GABAergic inhibition in the rat dorsal raphe neurons.
AB  - Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake-inducing
      neurons in the sleep-wake cycle and are controlled by gamma-aminobutyric acid
      (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of
      the rat DRN neurons and the role of nitric oxide (NO) and cation-chloride co
      transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co
      expressed in 74% of serotonergic DRN neurons and nNOS expression was higher
      during daytime (the sleep cycle) than that during nighttime (the wake cycle).
      GABAergic hyperpolarization of DRN neurons produced by GABAA receptor agonist
      muscimol was greater and the equilibrium potential of muscimol showed a
      hyperpolarizing shift during daytime compared to that during nighttime.
      Expression levels of potassium-chloride co-transporter 2 (KCC2) were higher
      during daytime than that during nighttime, whereas there were no changes in
      sodium-potassium-chloride co-transporter 1 (NKCC1) expression. With-no-lysine
      kinase (WNK) isoform 1 was more highly expressed during daytime than that during
      nighttime. Total Ste20-related proline alanine rich kinase (SPAK) and oxidative
      stress response kinase 1 (OSR1) were also higher during daytime than during
      nighttime, while there were no changes in phosphorylated SPAK and OSR1.
      Consistent with the findings during the sleep-wake cycle, ex vivo treatment of
      DRN slices with a NO donor sodium nitroprusside (SNP) increased the expression of
      KCC2, WNK1, WNK2, WNK3, SPAK, and OSR1, whilst decreasing phosphorylated SPAK.
      These results suggest that GABAergic synaptic inhibition of DRN serotonergic
      neurons shows daily changes during the sleep-wake cycle, which might be regulated
      by daily changes in nNOS-derived NO and WNK-SPAK/OSR1-KCC2 signaling.

PMID- 29596901
TI  - Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay
      in defensive behavior and aversive memory formation.
AB  - Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits
      sensations of fear and impending terror, and mediates predator defensive
      responses in rodents. In rats, pharmacological stimulation of the dorsolateral
      portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive
      conditioning that acts as an unconditioned stimulus (US). In the present work, we
      investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1
      receptors in the NMDA-dlPAG defensive response and in subsequent aversive
      learning. Rats were subjected to dlPAG NMDA infusion in an olfactory conditioned
      stimulus (CS) task allowing the evaluation of immediate and long-term defensive
      behavioral responses during CS presentation. The results indicated that an
      intermediate dose of NMDA (50 pmol) induced both immediate and long-term effects.
      A sub-effective dose of NMDA (25 pmol) was potentiated by the TRPV1 receptor
      agonist capsaicin (CAP, 1 nmol) and the CB1 receptor antagonist, AM251 (200
      pmol). CAP (10 nmol) or the combination of CAP (1 nmol) and AM251 (200 pmol)
      induced long-term effects without increasing immediate defensive responses. The
      glutamate release inhibitor riluzole (2 or 4 nmol) and the AMPA/kainate receptor
      antagonist DNQX (2 or 4 nmol) potentiated the immediate effects but blocked the
      long-term effects. The results showed that immediate defensive responses rely on
      NMDA receptors, and aversive learning on the fine-tuning of TRPV1, CB1,
      metabotropic glutamate and AMPA receptors located in pre- and postsynaptic
      membranes. In conclusion, the activity of the dlPAG determines core affective
      aspects of aversive memory formation controlled by local TRPV1/CB1 balance.

PMID- 29596902
TI  - Ceftolozane/tazobactam dose regimens in severely/morbidly obese patients with
      complicated intra-abdominal infection or complicated urinary tract infection.
AB  - Ceftolozane/tazobactam is approved for treatment of complicated intra-abdominal
      infection (cIAI) and complicated urinary tract infection (cUTI) with renal
      function-based dose adjustment. Given that creatinine clearance, body weight and
      sex are highly correlated in severely/morbidly obese patients, this study
      investigated whether approved dosing regimens for ceftolozane/tazobactam are
      appropriate in severely/morbidly obese patients based on simulated
      pharmacokinetic/pharmacodynamic target attainment, with confirmation from
      observed clinical outcomes data from the phase 3 clinical development programme.
      Using a previously published population pharmacokinetic model, 1000 patients were
      randomly sampled from an internal pooled database of 201 severely/morbidly obese
      patients (BMI >= 35 kg/m2) and were used for Monte Carlo simulation to test
      whether the labelled dose regimens can achieve >=90% probability of a target of
      32.2% (1-log kill) time above free ceftolozane concentration against pathogens at
      an MIC up to 8 mg/L. Clinical outcomes data for severely/morbidly obese patients
      with cIAI or cUTI from pivotal phase 3 studies were summarised to calculate
      clinical and composite cure rates as a complimentary support. With the approved
      renal function-based dosing regimens, >90% target attainment of bactericidal
      activity was achieved at MICs up to 8 mg/L in the simulated severely/morbidly
      obese patients with cIAI or cUTI, similar to target attainment in non-obese
      patients and further confirmed by phase 3 outcomes where cure rates in
      severely/morbidly obese patients and non-obese patients are similar. Approved
      dosing regimens of ceftolozane/tazobactam, adjusted according to renal function,
      can achieve adequate target attainment and high clinical cure rates in
      severely/morbidly obese patients with cIAI or cUTI.

PMID- 29596903
TI  - High prevalence of 16S rRNA methyltransferases among carbapenemase-producing
      Enterobacteriaceae in the UK and Ireland.
AB  - The emergence of 16S rRNA methyltransferases (16S RMTases) worldwide is a growing
      concern due to their ability to confer high-level resistance (minimum inhibitory
      concentrations (MICs) >256 mg/L) to all clinically relevant aminoglycosides. As
      the occurrence of 16S RMTases in the United Kingdom has not been investigated to
      date, we screened 806 Enterobacteriaceae isolates displaying high-level
      aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs >=64, >=32
      and >=32 mg/L, respectively) for 16S RMTases either by analysing whole-genome
      sequence (WGS) data (which were available for 449 isolates) or by polymerase
      chain reaction. A total of 94.5% (762/806) pan-aminoglycoside-resistant
      Enterobacteriaceae were positive for one or more 16S RMTase genes; armA was the
      most common (340, 44.6%) followed by rmtC (146, 19.2%), rmtF (137, 18.0%), rmtB
      (87, 11.4%) and various two-gene combinations (52, 6.8%). Most (93.4%; 712/762)
      16S RMTase producers also carried acquired carbapenemase genes, with blaNDM the
      most common (592/712; 83.1%). Additionally, high-risk bacterial clones associated
      with blaNDM were identified in the subset of isolates with WGS data. These
      included Escherichia coli sequence types (STs) 405 (21.8%, 19/87), 167 (20.7%,
      18/87) 410 (12.6%, 11/87) and K. pneumoniae STs 14 (35.6%, 112/315), 231 (15.6%,
      49/315) and 147 (10.5%, 33/315). These accounted for 4.2% (15/358), 5.0%
      (18/358), 3.1% (11/358), 28.2% (101/358), 3.1% (11/358) and 7.0% (25/358) blaNDM
      producing isolates, respectively. This study shows that 16S RMTases occur in the
      UK and Ireland and carbapenemases are particularly prevalent in 16S RMTase
      producing Enterobacteriaceae. This association poses a risk to the treatment of
      multidrug-resistant Gram-negative infections in the clinical setting.

PMID- 29596904
TI  - A Single-Arm Phase II Trial of Lenalidomide in Relapsing or Refractory Primary
      Cutaneous Large B-Cell Lymphoma, Leg Type.
AB  - Although the combination of rituximab and polychemotherapy has improved prognosis
      of primary cutaneous diffuse large B-cell lymphoma, leg type, the advanced age of
      patients limits therapeutic options in relapsing/refractory cases. A multicenter,
      single-arm, phase II trial was conducted to assess the benefits and safety of
      lenalidomide in refractory/relapsing primary cutaneous diffuse large B-cell
      lymphoma, leg type. The primary endpoint was the 6-month overall response rate.
      Secondary endpoints were 12-month overall response rate, overall and specific
      survival, duration of response, progression-free survival, safety, and
      identification of prognostic factors. Among the 19 patients included, the 6-month
      overall response rate was 26.3% (90% confidence interval [CI] = 11-47.6),
      including four complete responses and one partial response. At 12 months, there
      were still two complete responses and one partial response. Median progression
      free survival was 4 months. Median overall and specific survivals were 19.4 and
      23.8 months, respectively. Reduced doses tended to be associated with higher 6
      month overall response rate and progression-free survival. Absence of the
      MYD88L265P mutation was associated with a higher overall response under treatment
      (80.0% vs. 33.3%; P = 0.05). The most common grade 3 adverse events were
      hematologic. Two grade 5 adverse events occurred (sepsis and pulmonary embolism).
      Lenalidomide at reduced doses may allow prolonged responses in a few patients and
      represents a therapeutic option in relapsing/refractory primary cutaneous diffuse
      large B-cell lymphoma, leg type.

PMID- 29596905
TI  - Rapamycin Modulates Glucocorticoid Receptor Function, Blocks Atrophogene REDD1,
      and Protects Skin from Steroid Atrophy.
AB  - Glucocorticoids have excellent therapeutic properties; however, they cause
      significant adverse atrophogenic effects. The mTORC1 inhibitor REDD1 has been
      recently identified as a key mediator of glucocorticoid-induced atrophy. We
      performed computational screening of a connectivity map database to identify
      putative REDD1 inhibitors. The top selected candidates included rapamycin, which
      was unexpected because it inhibits pro-proliferative mTOR signaling. Indeed,
      rapamycin inhibited REDD1 induction by glucocorticoids dexamethasone, clobetasol
      propionate, and fluocinolone acetonide in keratinocytes, lymphoid cells, and
      mouse skin. We also showed blunting of glucocorticoid-induced REDD1 induction by
      either catalytic inhibitor of mTORC1/2 (OSI-027) or genetic inhibition of mTORC1,
      highlighting role of mTOR in glucocorticoid receptor signaling. Moreover,
      rapamycin inhibited glucocorticoid receptor phosphorylation, nuclear
      translocation, and loading on glucocorticoid-responsive elements in REDD1
      promoter. Using microarrays, we quantified a global effect of rapamycin on gene
      expression regulation by fluocinolone acetonide in human keratinocytes. Rapamycin
      inhibited activation of glucocorticoid receptor target genes yet enhanced the
      repression of pro-proliferative and proinflammatory genes. Remarkably, rapamycin
      protected skin against glucocorticoid-induced atrophy but had no effect on the
      glucocorticoid anti-inflammatory activity in different in vivo models, suggesting
      the clinical potential of combining rapamycin with glucocorticoids for the
      treatment of inflammatory diseases.

PMID- 29596906
TI  - Atrial electrogram quality in single-pass defibrillator leads with floating
      atrial bipole in patients with permanent atrial fibrillation and cardiac
      resynchronization therapy.
AB  - : Many patients receiving cardiac resynchronization therapy (CRT) suffer from
      permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important
      to direct pharmacological or interventional treatment as well as maintaining AV
      synchronous biventricular pacing if sinus rhythm can be restored. A single pass
      single-coil defibrillator lead with a floating atrial bipole has been shown to
      obtain reliable information about the atrial rhythm but has never been employed
      in a CRT-system. The purpose of this study was to assess the feasibility of
      implanting a single coil right ventricular ICD lead with a floating atrial bipole
      and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator
      recipients with permanent AF. METHODS AND RESULTS: Seventeen patients (16 males,
      mean age 73 +/- 6 years, mean EF 25 +/- 5%) with permanent AF and an indication
      for CRT-defibrillator placement were implanted with a designated CRT-D system
      comprising a single pass defibrillator lead with a atrial floating bipole. They
      were followed-up for 103 +/- 22 days using remote monitoring for AEGM
      transmission. All patients had at last one AEGM suitable for atrial rhythm
      diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment.
      Four patients were discharged in sinus rhythm and one reverted to AF during
      follow-up. CONCLUSION: Atrial electrograms retrieved from a single-pass
      defibrillator lead with a floating atrial bipole can be reliably used for atrial
      rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass
      ventricular defibrillator lead with a floating bipole can be considered in this
      population.

PMID- 29596908
TI  - The discrimination of magnitude: A review and theoretical analysis.
AB  - In a discrimination based on magnitude, the same stimulus is presented at two
      different magnitudes and an outcome, such as food, is signalled by one magnitude
      but not the other. The review presented in the first part of the article shows
      that, in general, such a discrimination is acquired more readily when the outcome
      is signalled by the larger rather than the smaller of the two magnitudes. This
      asymmetry is observed with magnitudes based on sound, odour, temporal duration,
      quantity, and physical length. The second part of the article, explores the
      implications of this pattern of results for the theory of discrimination learning
      presented by Pearce (1994). The asymmetry found with discriminations based on
      magnitude contradicts predictions derived from the original version of the
      theory, but it can be explained by a modified version. The asymmetry also has
      important implications for understanding how animals represent magnitudes.

PMID- 29596907
TI  - Urban-Rural Inequities in the Parental Attitudes and Beliefs Towards Human
      Papillomavirus Infection, Cervical Cancer, and Human Papillomavirus Vaccine in
      Mysore, India.
AB  - STUDY OBJECTIVE: The aim of this study was to compare the parental attitudes and
      beliefs about human papillomavirus (HPV), cervical cancer, and HPV vaccine
      between urban and rural areas, India. DESIGN: Cross-sectional. SETTING: Mysore,
      India. PARTICIPANTS: Parents of school-going adolescent girls. INTERVENTIONS:
      Parents completed a self-administered questionnaire. MAIN OUTCOME MEASURES:
      Attitudes and beliefs about HPV, cervical cancer, and HPV vaccine. RESULTS: A
      total of 1609 parents from urban (n = 778) and rural (n = 831) areas participated
      in this study. Most of the parents had never heard about HPV (73.6%), did not
      know that their daughters could get an HPV infection (62.7%) or cervical cancer
      (64.1%) in the future, and believed that HPV vaccine was not effective (67.1%).
      Parents living in the urban area were more likely to believe that HPV infection
      (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.43-5.06) and
      cervical cancer (aOR, 2.68; 95% CI, 1.83-3.91) could cause serious health
      problems than those living in the rural area. The odds of agreeing that HPV
      vaccination will make girls sexually active was lower among urban than rural
      parents (aOR, 0.55; 95% CI, 0.33-0.94). There was no significant difference among
      parents in the urban and rural areas in their beliefs about susceptibility of
      their daughter to HPV infection or cervical cancer, and beliefs about the safety
      and ability of HPV vaccine to protect against cervical cancer. CONCLUSION: Rural
      parents might be reluctant to recommend behaviors that can help prevent HPV
      infection and cervical cancer such as HPV vaccination for their daughters.

PMID- 29596909
TI  - Protein-nucleic acid interactions of LINE-1 ORF1p.
AB  - Long interspersed nuclear element 1 (LINE-1 or L1) is the dominant
      retrotransposon in mammalian genomes. L1 encodes two proteins ORF1p and ORF2p
      that are required for retrotransposition. ORF2p functions as the replicase. ORF1p
      is a coiled coil-mediated trimeric, high affinity RNA binding protein that
      packages its full- length coding transcript into an ORF2p-containing
      ribonucleoprotein (RNP) complex, the retrotransposition intermediate. ORF1p also
      is a nucleic acid chaperone that presumably facilitates the proposed nucleic acid
      remodeling steps involved in retrotransposition. Although detailed mechanistic
      understanding of ORF1p function in this process is lacking, recent studies showed
      that the rate at which ORF1p can form stable nucleic acid-bound oligomers in
      vitro is positively correlated with formation of an active L1 RNP as assayed in
      vivo using a cell culture-based retrotransposition assay. This rate was sensitive
      to minor amino acid changes in the coiled coil domain, which had no effect on
      nucleic acid chaperone activity. Additional studies linking the complex nucleic
      acid binding properties to the conformational changes of the protein are needed
      to understand how ORF1p facilitates retrotransposition.

PMID- 29596910
TI  - Intrinsic and Extrinsic Regulation of PD-L2 Expression in Oncogene-Driven Non
      Small Cell Lung Cancer.
AB  - INTRODUCTION: The interaction of programmed cell death ligand 2 (PD-L2) with
      programmed cell death 1 is implicated in tumor immune escape. The regulation of
      PD-L2 expression in tumor cells has remained unclear, however. We here examined
      intrinsic and extrinsic regulation of PD-L2 expression in NSCLC. METHODS: PD-L2
      expression was evaluated by reverse transcription and real-time polymerase chain
      reaction analysis and by flow cytometry. RESULTS: BEAS-2B cells stably expressing
      an activated mutant form of EGFR or the echinoderm microtubule associated protein
      like 4 (EML4)-ALK receptor tyrosine kinase fusion oncoprotein manifested
      increased expression of PD-L2 at both the mRNA and protein levels. Furthermore,
      treatment of NSCLC cell lines that harbor such driver oncogenes with
      corresponding EGFR or ALK tyrosine kinase inhibitors or depletion of EGFR or ALK
      by small interfering RNA transfection suppressed expression of PD-L2,
      demonstrating that activating EGFR mutations or echinoderm microtubule associated
      protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) fusion
      intrinsically induce PD-L2 expression. We also found that interferon gamma (IFN
      gamma) extrinsically induced expression of PD-L2 through signal transducer and
      activator of transcription 1 signaling in NSCLC cells. Oncogene-driven expression
      of PD-L2 in NSCLC cells was inhibited by knockdown of the transcription factors
      signal transducer and activator of transcription 3 (STAT3) or c-FOS. IFN-gamma
      also activated STAT3 and c-FOS, suggesting that these proteins may also
      contribute to the extrinsic induction of PD-L2 expression. CONCLUSIONS:
      Expression of PD-L2 is induced intrinsically by activating EGFR mutations or EML4
      ALK fusion and extrinsically by IFN-gamma, with STAT3 and c-FOS possibly
      contributing to both intrinsic and extrinsic pathways. Our results thus provide
      insight into the complexity of tumor immune escape in NSCLC.

PMID- 29596911
TI  - Concurrent Acquired BRAF V600E Mutation and MET Amplification as Resistance
      Mechanism of First-Line Osimertinib Treatment in a Patient with EGFR-Mutated
      NSCLC.

PMID- 29596912
TI  - Characterization of a large UNC13D gene duplication in a patient with familial
      hemophagocytic lymphohistiocytosis type 3.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) type 3 is a life-threatening
      immune dysregulation syndrome caused by mutations in the UNC13D gene, encoding
      the munc13-4 protein, which is important for function of cytotoxic lymphocytes.
      FHL3 accounts for 30-40% of FHL cases, and more than 100 mutations in the UNC13D
      gene have been described to date. We describe the first case of FHL3 carrying an
      intragenic duplication of UNC13D, apparently mediated by recombination of Alu
      elements. NK cell degranulation and munc13-4 protein expression assays are useful
      for early identification of such mutations, which may be missed by analysis of
      genomic DNA alone.

PMID- 29596913
TI  - Wing vein development in the sawfly Athalia rosae is regulated by spatial
      transcription of Dpp/BMP signaling components.
AB  - Wing venation among insects serves as an excellent model to address how
      diversified patterns are produced. Previous studies suggest that evolutionarily
      conserved Decapentaplegic (Dpp)/Bone Morphogenetic Protein (BMP) signal plays a
      critical role in wing vein development in the dipteran Drosophila melanogaster
      and the hymenopteran sawfly Athalia rosae. In sawfly, dpp is ubiquitously
      expressed in the wing during prepupal stages, but Dpp/BMP signal is localized in
      the future vein cells. Since localized BMP signaling involves BMP binding protein
      Crossveinless (Cv), redistribution of BMP ligands appears to be crucial for
      sawfly wing vein formation. However, how ubiquitously expressed ligands lead to a
      localized signal remains to be addressed. Here, we found that BMP binding protein
      short gastrulation (Sog) is highly expressed in the intervein cells. Our data
      also reveal that BMP type I receptors thickveins (Tkv) and saxophone (Sax) are
      highly expressed in intervein cells and at lower levels in the vein progenitor
      cells. RNAi knockdown of Ar-tkv or Ar-sax indicates that both receptors are
      required for localized BMP signaling in the wing vein progenitor cells. Taken
      together, our data suggest that spatial transcription of core- and co-factors of
      the BMP pathway sustain localized BMP signaling during sawfly wing vein
      development.

PMID- 29596915
TI  - Structural Ensemble Modulation upon Small-Molecule Binding to Disordered
      Proteins.
AB  - Over the past decade, there has been a growing interest in investigating whether
      disordered proteins can be targeted for clinical purposes using small molecules
      [1-8]. While small-molecule binding to disordered proteins can be seen as
      unorthodox, examples of this phenomenon have been reported. In order to
      rationalize these observations, a variety of models are emerging, sometimes in
      apparent contradiction. Here, we offer a "structural ensemble modulation" view as
      an attempt to clarify the language, organize concepts, and facilitate the
      comparison of different studies. In doing so, we hope to promote the
      understanding of the general principles underlying this phenomenon toward the
      development of novel therapeutic compounds targeting disordered proteins, which
      are prevalent in a wide range of human diseases [1-8].

PMID- 29596914
TI  - VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen
      Binding by Non-Ig-based Antibodies.
AB  - Variable lymphocyte receptors (VLRs) are unconventional adaptive immune receptors
      relatively recently discovered in the phylogenetically ancient jawless
      vertebrates, lamprey and hagfish. VLRs bind antigens using a leucine-rich repeat
      fold and are the only known adaptive immune receptors that do not utilize an
      immunoglobulin fold for antigen recognition. While immunoglobulin antibodies have
      been studied extensively, there are comparatively few studies on antigen
      recognition by VLRs, particularly for protein antigens. Here we report isolation,
      functional and structural characterization of three VLRs that bind the protein
      toll-like receptor 5 (TLR5) from zebrafish. Two of the VLRs block binding of TLR5
      to its cognate ligand flagellin in functional assays using reporter cells. Co
      crystal structures revealed that these VLRs bind to two different epitopes on
      TLR5, both of which include regions involved in flagellin binding. Our work here
      demonstrates that the lamprey adaptive immune system can be used to generate high
      affinity VLR clones that recognize different epitopes and differentially impact
      natural ligand binding to a protein antigen.

PMID- 29596916
TI  - Some Surprising Implications of NMR-directed Simulations of Substrate Recognition
      and Binding by Cytochrome P450cam (CYP101A1).
AB  - Cytochrome P450cam (CYP101A1) catalyzes the stereospecific 5-exo hydroxylation of
      d-camphor by molecular oxygen. Previously, residual dipolar couplings measured
      for backbone amide 1H-15N correlations in both substrate-free and bound forms of
      CYP101A1 were used as restraints in soft annealing molecular dynamic simulations
      in order to identify average conformations of the enzyme with and without
      substrate bound. Multiple substrate-dependent conformational changes remote from
      the enzyme active site were identified, and site-directed mutagenesis and
      activity assays confirmed the importance of these changes in substrate
      recognition. The current work makes use of perturbation response scanning (PRS)
      and umbrella sampling molecular dynamic of the residual dipolar coupling-derived
      CYP101A1 structures to probe the roles of remote structural features in enforcing
      the regio- and stereospecific nature of the hydroxylation reaction catalyzed by
      CYP101A1. An improper dihedral angle Psi was defined and used to maintain
      substrate orientation in the CYP101A1 active site, and it was observed that
      different values of Psi result in different PRS response maps. Umbrella sampling
      methods show that the free energy of the system is sensitive to Psi, and bound
      substrate forms an important mechanical link in the transmission of mechanical
      coupling through the enzyme structure. Finally, a qualitative approach to
      interpreting PRS maps in terms of the roles of secondary structural features is
      proposed.

PMID- 29596917
TI  - Clustering of unhealthy lifestyle behaviours and associations with perceived and
      actual weight status among primary school children in China: A nationally
      representative cross-sectional study.
AB  - Few studies have focused on clustering of unhealthy lifestyle behaviours among
      primary school children and potential associations with perceived and actual
      weight status. An index was constructed from adding up 13 unhealthy behaviours
      measured by survey responses. Multilevel linear regressions were used to analyse
      associations between child personal characteristics, perceived and actual weight
      status with the unhealthy lifestyle index among 11,157 children in primary
      schools across China. Parental and area factors were also taken into account,
      including education, weight status, physical activity, urban/rural and area
      socioeconomic circumstances. The unhealthy lifestyle index normally distributed,
      with 84.5% of children reporting between 2 and 6 unhealthy behaviours. Boys
      reported more unhealthy behaviours compared with girls (coefficient 0.32, 95%CI
      0.26 to 0.37) and children in urban areas had fewer unhealthy behaviours than
      their rural counterparts (-0.29, 95%CI -0.56 to -0.03). An interaction revealed
      stronger 'protective' effects of living in cities for girls than boys, which were
      not explained by differences in child overweight/obesity. More unhealthy
      behaviours were characteristic of children in more affluent areas, and of those
      born to mothers and/or fathers with lower educational attainment. Children who
      perceived themselves as overweight or underweight both scored higher on the
      unhealthy lifestyle index. Unhealthy behaviours that could increase the risk of
      childhood obesity are common among Chinese primary school children, particularly
      among boys in cities, those in more affluent areas and with parents with lower
      education. There was no effect of actual weight status on number of unhealthy
      behaviours. Perceived, but not actual weight status, was also a significant
      correlate of unhealthy behaviours. Clustering of unhealthy lifestyle behaviours
      that could increase the risk of childhood obesity are common among Chinese
      primary school children, particularly among boys in cities, those in more
      affluent areas and with parents with lower education. Perceived, but not actual
      weight status, was also a significant correlate of unhealthy lifestyle. This has
      important implications for public health because understanding clustering of
      unhealthy lifestyle behaviours can be used to assist in the development of
      targeted obesity prevention initiatives.

PMID- 29596918
TI  - Association between exercise type and the decline in instrumental activities of
      daily living in community-dwelling older women: A 4-year prospective study.
AB  - Exercise can delay the decline of instrumental activities of daily living (IADL),
      although it remains unclear which specific exercise types are associated with
      such a delay. This 4-year prospective cohort study in Japan aimed to identify the
      longitudinal associations between exercise types and the onset of IADL decline in
      older women. Between 2008 and 2012, 1082 community-dwelling older women aged >=75
      years participated in this study. Participations in 16 exercise types based on a
      face-to-face interview at baseline were used as independent variables. The
      primary study outcome was a decline in IADL as assessed using the instrumental
      self-maintenance subscale of the Tokyo Metropolitan Institute of Gerontology
      index of competence. An IADL decline was defined as a decrease of >=1 point over
      the 4-year follow-up period and was used as the dependent variable. Adjusted odds
      ratios (ORs) and 95% confident intervals (CIs) for IADL decline based on
      participation or non-participation in each exercise type were obtained using
      logistic regression analyses. An IADL decline was observed in 151 participants
      (13.9%) over the 4-year follow-up period. After adjustment for potential
      confounders, participation in calisthenics had a significantly lower OR (0.62;
      95% CI 0.42-0.90) for IADL decline. There were no significant associations
      between other specific exercise types and IADL decline. In conclusion,
      participation in calisthenics was significantly and independently associated with
      delayed IADL decline in older women aged >=75 years. Thus, calisthenics may be a
      useful exercise to slow IADL decline in this age group.

PMID- 29596919
TI  - Reconstruction of radial bone defect in rat by calcium silicate biomaterials.
AB  - AIMS: Despite many attempts, an appropriate therapeutic method has not yet been
      found to enhance bone formation, mechanical strength and structural and
      functional performances of large bone defects. In the present study, the bone
      regenerative potential of calcium silicate (CS) biomaterials combined with
      chitosan (CH) as calcium silicate/chitosan (CSC) scaffold was investigated in a
      critical radial bone defect in a rat model. MAIN METHODS: The bioimplants were
      bilaterally implanted in the defects of 20 adult Sprague-Dawley rats. The rats
      were euthanized and the bone specimens were harvested at the 56th postoperative
      day. The healed radial bones were evaluated by three-dimensional CT, radiology,
      histomorphometric analysis, biomechanics, and scanning electron microscopy. KEY
      FINDINGS: The XRD analysis of the CS biomaterial showed its similarity to
      wollastonite (beta-SiCO3). The degradation rate of the CSC scaffold was much
      higher and it induced milder inflammatory reaction when compared to the CH alone.
      More bone formation and higher biomechanical performance were observed in the CSC
      treated group in comparison with the CH treated ones in histological, CT scan and
      biomechanical examinations. Scanning electron microscopic observation
      demonstrated the formation of more hydroxyapatite crystals in the defects treated
      with CSC. SIGNIFICANCE: This study showed that the CSC biomaterials could be used
      as proper biodegradable materials in the field of bone reconstruction and tissue
      engineering.

PMID- 29596920
TI  - The involvement of sympathetic nervous system in essence of chicken-facilitated
      physiological adaption and circadian resetting.
AB  - AIM: The impact of the sympathetic nervous system (SNS) on the regulation of
      circadian rhythm and physiological functions is still not clear. Previous studies
      have found that essence of chicken (EC) supplementation facilitated the
      physiological adaption and circadian resetting in rats subjected to jet lag.
      Herein, the effects of SNS on the circadian clock and the hypothesis that EC
      induced acceleration of circadian resetting is dependent on the SNS are
      investigated. MAIN METHODS: Male Wistar rats with superior cervical
      ganglionectomy (SCGx) were used to investigate the role of the SNS in circadian
      rhythm and physiological functions. SCGx rats were further fed with or without EC
      containing diet for 2 weeks and subjected to artificial jet lag. KEY FINDINGS:
      Loss of SNS did not affect the circadian rhythm both in the hypothalamic
      suprachiasmatic nuclei (SCN) and peripheral clocks, including the liver and
      heart. The serum lipid levels were increased significantly in SCGx rats, together
      with the up-regulation of lipogenic gene expression in the liver and slight
      effect on serum hormones. The quicker resetting process of the clock genes in
      peripheral tissues of EC-fed rats was abolished after SCGx. In contrast, the
      phase shift of serum melatonin and corticosterone were faster in EC-fed rats,
      compared to that of control rats. SIGNIFICANCE: The SNS controls different
      aspects of physiological functions, and it has little effect on circadian system
      under normal light/dark condition. The effects EC on peripheral circadian
      synchrony and physiological functions were dependent on, at least partly, through
      the regulation of sympathetic nerve function.

PMID- 29596922
TI  - Vitamin D and toll like receptors.
AB  - It has been demonstrated that vitamin D (VD) significantly modulates immune
      responses. Toll like receptors (TLRs) are the main innate immunity receptors
      which are expressed on the cell membrane and intracellular vesicles and recognize
      several pathogen associated molecular patterns (PAMPs) and damage associated
      molecular patterns (DAMPs) to induce immune responses. Based on the important
      roles played by TLRs in physiologic and pathologic functions of immune responses
      and due to the immunomodulatory functions of VD, it has been hypothesized that VD
      may present its immunomodulatory functions via modulation of TLRs. This review
      article collates recent studies regarding the interactions between VD and TLRs
      and discussed the controversial investigations.

PMID- 29596921
TI  - N-(3-oxododecanoyl)-l-homoserine lactone modulates mitochondrial function and
      suppresses proliferation in intestinal goblet cells.
AB  - AIMS: The quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (C12
      HSL), produced by the Gram negative human pathogenic bacterium Pseudomonas
      aeruginosa, modulates mammalian cell behavior. Our previous findings suggested
      that C12-HSL rapidly decreases viability and induces apoptosis in LS174T goblet
      cells. MAIN METHODS: In this study, the effects of 100 MUM C12-HSL on
      mitochondrial function and cell proliferation in LS174T cells treated for 4 h
      were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA) and
      flow cytometry. KEY FINDINGS: The results showed that the activities of
      mitochondrial respiratory chain complexes IV and V were significantly increased
      (P < 0.05) in LS174T cells after C12-HSL treatment, with elevated intracellular
      ATP generation (P < 0.05). Flow cytometry analysis revealed significantly
      increased intracellular Ca2+ levels (P < 0.05), as well as disrupted
      mitochondrial activity and cell cycle arrest upon C12-HSL treatment. Apoptosis
      and cell proliferation related genes showed markedly altered expression levels (P
      < 0.05) in LS174T cells after C12-HSL treatment. Moreover, the paraoxonase 2
      (PON2) inhibitor TQ416 (1 MUM) remarkably reversed the above C12-HSL associated
      effects in LS174T cells. SIGNIFICANCE: These findings indicated that C12-HSL
      alters mitochondrial energy production and function, and inhibits cell
      proliferation in LS174T cells, with PON2 involvement.

PMID- 29596923
TI  - Effects of continuous bisphenol A exposure from early gestation on 90 day old rat
      testes function and sperm molecular profiles: A CLARITY-BPA consortium study.
AB  - Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as
      an endocrine disrupting compound (EDC). There is growing concern that early life
      exposures to EDCs, such as BPA, can adversely affect the male reproductive tract
      and function. This study was conducted as part of the Consortium Linking Academic
      and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the
      toxicities associated with continuous exposure to BPA from early gestation, and
      to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague
      Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and
      their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA
      (2.5, 25, 250, 2500, 25,000, 250,000 MUg/kg/d) or vehicle control. At PND 90, the
      testes and sperm were collected for evaluation. The testes were histologically
      evaluated for altered germ cell apoptosis, sperm production, and altered
      spermiation. RNA and DNA isolated from sperm were assessed for elicited changes
      in global mRNA transcript abundance and altered DNA methylation. Effects of BPA
      were observed in changes in body, testis and epididymis weights only at the
      highest administered dose of BPA of 250,000 MUg/kg/d. Genome-wide transcriptomic
      and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA
      methylation levels. These data indicate that prolonged exposure starting in utero
      to BPA over a wide range of levels has little, if any, impact on the testes and
      sperm molecular profiles of 90 day old rats as assessed by the histopathologic,
      morphometric, and molecular endpoints evaluated.

PMID- 29596924
TI  - Do in vitro assays in rat primary neurons predict drug-induced seizure liability
      in humans?
AB  - Drug-induced seizures contribute to the high attrition rate of pharmaceutical
      compounds in development. The assessment of drug-induced seizure liability
      generally occurs in later phases of development using low throughput and
      intensive in vivo assays. In the present study, we evaluated the potential of an
      in vitro assay for detecting drug-induced seizure risk compared to evaluation in
      rats in vivo. We investigated the effects of 8 reference drugs with a known
      seizurogenic risk using micro-electrode array (MEA) recordings from freshly
      dissociated rat primary neurons cultured on 48-well dishes for 28 days, compared
      to their effects on the EEG in anesthetized rats. In addition, we evaluated
      functional responses and mRNA expression levels of different receptors in vitro
      to understand the potential mechanisms of drug-induced seizure risk. Combining
      the functional MEA in vitro data with concomitant gene expression allowed us to
      identify several potential molecular targets that might explain the drug-induced
      seizures occurring in both rats and humans. Our data 1) demonstrate the utility
      of a group of MEA parameters for detecting potential drug-induced seizure risk in
      vitro; 2) suggest that an in vitro MEA assay with rat primary neurons may have
      advantages over an in vivo rat model; and 3) identify potential mechanisms for
      the discordance between rat assays and human seizure risk for certain
      seizurogenic drugs.

PMID- 29596926
TI  - Effects of prenatal exposure to triclosan on the liver transcriptome in chicken
      embryos.
AB  - Triclosan (TCS), a commonly used antimicrobial compound, has recently been
      detected in the eggs of wild avian species. Exposure to TCS in rodents is known
      to interfere with thyroid hormone (TH), disrupt immune responses and cause liver
      disease. However, no attempt has been made to clarify the effects of TCS in avian
      species. The aim of this study is therefore to evaluate the toxic effects of in
      ovo exposure to TCS and explore the molecular mechanism by transcriptome analysis
      in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos
      were treated with graded concentration of TCS (0.1, 1 and 10 MUg/g egg) at
      Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to
      HHS 46. At the administration of 10 MUg TCS/g egg, embryo mortality increased
      from 20% in control to 37% accompanied with 8% attenuation in tarsus length.
      While liver somatic index (LSI) in TCS treatments was enhanced, statistical
      difference was only observed at the treatment of 0.1 MUg TCS/g egg in females.
      The up-regulation of several crucial differentially expressed genes (DEGs) in
      transcriptome analysis suggested that TCS induced xenobiotic metabolism (e.g.
      CYP2C23a, CYP2C45 and CYP3A37 in males; CYP2C45 in females) and activated the
      thyroid hormone receptor (THR) - mediated downstream signaling (e.g. THRSPB and
      DIO2 in males; THRSPB in females). In females, TCS may further activate the
      lipogenesis signaling (e.g. ACSL5, ELOVL2) and repress the lipolysis signaling
      (e.g. ABHD5, ACAT2). A battery of enriched transcription factors in relation to
      these TCS-induced signaling and phenotypes were found, including activated
      SREBF1, PPARa, LXRa, and LXRb in males and activated GLI2 in females; COUP-TFII
      was predicted to be suppressed in both genders. Finally, we developed adverse
      outcome pathways (AOPs) that provide insights into the molecular mechanisms
      underlying the alteration of phenotypes.

PMID- 29596925
TI  - Association of pesticide exposure with human congenital abnormalities.
AB  - Human pesticide exposure can occur both occupationally and environmentally during
      manufacture and after the application of indoor and outdoor pesticides, as well
      as through consumption via residues in food and water. There is evidence from
      experimental studies that numerous pesticides, either in isolation or in
      combination, act as endocrine disruptors, neurodevelopmental toxicants,
      immunotoxicants, and carcinogens. We reviewed the international literature on
      this subject for the years between 1990 and 2017. The studies were considered in
      this review through MEDLINE and WHO resources. Out of the n = 1817 studies
      identified, n = 94 were reviewed because they fulfilled criteria of validity and
      addressed associations of interest. Epidemiological studies have provided limited
      evidence linking pre- and post-natal exposure to pesticides with cancers in
      childhood, neurological deficits, fetal death, intrauterine growth restriction,
      preterm birth, and congenital abnormalities (CAs). In this review, the potential
      association between pesticide exposure and the appearance of some human CAs
      (including among others musculoskeletal abnormalities; neural tube defects;
      urogenital and cardiovascular abnormalities) was investigated. A trend towards a
      positive association between environmental or occupational exposure to some
      pesticides and some CAs was detected, but this association remains to be
      substantiated. Main limitations of the review include inadequate exposure
      assessment and limited sample size. Adequately powered studies with precise
      exposure assessments such as biomonitoring, are warranted to clarify with
      certainty the potential association between pesticide exposure and human CAs.

PMID- 29596927
TI  - Gene expression profiling of human bronchial epithelial cells exposed to fine
      particulate matter (PM2.5) from biomass combustion.

PMID- 29596928
TI  - Cardiac safety evaluation in zebrafish and in silico ADME prediction of
      cephalosporins with an aminothiazoyl ring at the C-7 position.
AB  - Systems toxicology approaches have been used as important tools in the drug
      discovery and medicine quality control processes. The aim of this study was to
      assess the pharmacokinetic and toxicity properties of cephalosporins with an
      aminothiazoyl ring at the C-7 position (CATRs). Cardiac toxicity of the compounds
      was assessed in zebrafish embryos, and it was determined that CATRs disturbed the
      formation and development of the heart in a dose-dependent manner. Differentially
      expressed genes (DEGs) related to the heart were also identified by transcriptome
      analysis, and co-DEGs were obtained in the protein-protein interaction (PPI)
      network. Several Gene Ontology (GO) terms and pathways that were enriched by DEGs
      were identified, and the most significantly enriched pathways were adrenergic
      signaling in cardiomyocytes, cardiac muscle contraction, and vascular smooth
      muscle contraction. Combined molecular docking results elucidated that cardiac
      toxicity mainly depends on the mother nucleus structure 7-aminocephalosporanic
      acid (7-ACA). The predicted absorption, distribution, metabolism and excretion
      (ADME) profile suggests that there is a modification at the C-3 side chain of 7
      ACA that could change the compound distribution in vivo. The 7-ACA mother nucleus
      is responsible for the CATRs induced cardiac toxicity, and the three DEGs (nppa,
      adra2c, and tnni1c) may potentially be utilized as novel biomarkers for CATRs.
      Our results show that zebrafish embryos may be used to reveal the pathways of
      cardiac toxicity and they play a vital role in drug safety assessments.

PMID- 29596929
TI  - Preparation, characterization, and biodegradation of poly(butylene
      succinate)/cellulose triacetate blends.
AB  - Poly(butylene succinate) (PBS) and cellulose triacetate (CT) were blended using
      chloroform as solvent. The solid-state properties of PBS/CT blends were confirmed
      by Fourier transform infrared spectroscopy (FTIR), differential scanning
      calorimetry (DSC), X-ray diffraction (XRD), thermogravimetric analysis, scanning
      electron microscopy (SEM), and water contact angle measurements. FTIR results
      show that PBS and CT were physically blended. Tensile strength was not
      distinguished when the weight percent of CT was <15%, and Young's modulus
      increased gradually with increasing CT. DSC and XRD results show that the
      crystals were homogeneous, and crystallinity had no apparent decrease when <10%
      CT was added to the PBS matrix. However, the addition of more CT components could
      destroy the crystal behavior of PBS. SEM showed that no phase separation occurred
      between the two materials. The addition of CT increased the hydrophilicity of
      PBS/CT1-15 blends. The weight loss was nearly 90% after 16h of degradation for
      PBS/CT10. The appropriate proportion of PBS to CT was 90:10.

PMID- 29596930
TI  - Evaluation of nitriloacetic acid modified cellulose film on adsorption of
      methylene blue.
AB  - A novel composite film (MCalphaN) based on microcrystalline cellulose (MCC) and
      nitrilotriacetic acid anhydride (NTAA) was prepared via casting method for the
      adsorption of methylene blue (MB) from aqueous solution. FT-IR, XRD, elemental
      analysis and TGA analysis demonstrated the success of modification. The swelling
      behavior, mechanical properties and MB adsorption performance of the modified
      MCalphaN films were improved obviously. The recycling study illustrated that MC2N
      film could be recycled and exhibited constant adsorption performance for five
      successful runs. In addition, mechanism study found that adsorption behavior of
      the composite films was better consistent with the pseudo-second order kinetic
      model and the Langmuir model. All the results suggested that the MCalphaN films
      could be considered as a promising candidate for dye wastewater treatment.

PMID- 29596931
TI  - Fabrication and characterization of electrospun nanofibers using flaxseed (Linum
      usitatissimum) mucilage.
AB  - The spin ability of flaxseed mucilage (FM) as a new source was evaluated through
      electrospinning. At various experimental conditions and different solution
      properties, it was impossible to fabricate FM nanofiber. Thus, polyvinyl alcohol
      (PVA) was applied as co-polymer to facilitate nanofiber formation. In terms of
      morphology, FM:polyvinyl alcohol (PVA) nanofiber using a mixture of 3% FM
      solution and 12% (PVA) solution at ratio of 60:40 was selected as the best
      sample. The physicochemical properties of the nanofiber was evaluated by scanning
      electron microscopy (SEM), fourier transform infrared (FTIR), differential
      scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and X-ray
      diffraction (XRD). SEM images showed beadless, uniform and smooth nanofibers with
      an average diameter of 230nm. Based on DSC and TGA results, the thermal stability
      of the nanofiber was improved by adding PVA. FTIR data revealed that there was no
      chemical interaction between functional groups of FM and PVA in the nanofiber.

PMID- 29596932
TI  - Extraction, characterisation and antioxidant activity of Allium sativum
      polysaccharide.
AB  - Extraction and antioxidant activity of polysaccharide from Allium sativum were
      investigated. The crude polysaccharide was obtained by the hot-water extraction
      method. The molecular weight of polysaccharide deproteinized with CaCl2 was
      7.35*103. It indicated that polysaccharide from Allium sativum consisted of three
      monosaccharides, namely fructose, glucose, and galactose by HPLC. The
      polysaccharide had the beta-glycosidic bond. Moreover, it was proved that the
      polysaccharide had the potential scavenging ability to superoxide anions and
      hydroxyl radicals. So, it should be a potential antioxidant.

PMID- 29596933
TI  - Identification, purification, biochemical and mass spectrometric characterization
      of novel phycobiliproteins from a marine red alga, Centroceras clavulatum.
AB  - Phycobilisomes are light-harvesting protein complexes and are widely distributed
      in red algae and cyanobacteria. Each phycobilisome contains highly fluorescent
      protein components called phycobiliproteins. Based upon the distinct
      physiochemical properties, phycobiliproteins are classified as allophycocyanin,
      phycocyanin, phycoerythrin and phycoerythrocyanin. In the present study, we
      describe purification and structural characterization of a novel phycocyanin and
      phycoerythrin isolated from a marine red macroalga, Centroceras clavulatum. The
      absorbance and fluorescence studies indicated that the purified proteins belong
      to R-Phycocyanin (R-PC) and R-Phycoerythrin (R-PE). The single bands under native
      polyacrylamide gel electrophoresis revealed the intact molecular weights of R-PC
      and R-PE as 110kDa and 250kDa. The polypeptide compositions of the two proteins
      were demonstrated by SDS-PAGE. The result showed that R-PC contains two bands at
      17 and 21kDa and were identified as alpha and beta subunits through mass
      spectrometry based proteomics experiments. SDS-PAGE of R-PE showed three distinct
      bands at 18, 19 and 35kDa and was subsequently identified as alpha, beta and
      gamma subunits. The near-complete amino acid sequences of alpha and beta subunits
      of R-PC and R-PE were derived from mass spectrometric data combined with Mascot
      software and multiple de novo sequencing tools followed by homology search and
      manual validation.

PMID- 29596934
TI  - A non-woven fabric wound dressing containing layer - by - layer deposited
      hyaluronic acid and chitosan.
AB  - Novel wound dressings composed of non-woven cotton (NWC) fabric and multilayer of
      hyaluronan (HA) and chitosan were built using layer-by-layer assembly technique.
      Factors affecting the building up of that dressings such as HA concentration,
      number of coating layers and nitrogen content of the NWC fabric quaternized form
      were studied. Meanwhile, some physico-chemical properties of such dressings were
      investigated. Moreover, to enhance the antibacterial properties of the
      aforementioned dressings, Silver nano-particles (Ag NPs) were prepared and
      incorporated as a functional additive in the final HA layer of such dressings.
      Factors affecting the building up of that dressings such as HA concentration,
      number of coating layers and nitrogen content of the NWC fabric quaternized form
      were studied. The results obtained showed that: i) increasing of HA concentration
      from 0.25 to 1.0% is accompanied by a gradual reduction in the swelling
      properties and an improvement in the gel fractionas as well as antibacterial
      properties of treated fabric along with a decreasing in extents of stiffness, air
      permeability and the relative water vapor permeability of treated fabric, ii)
      increasing of steeping time of coated samples results in an improvement in
      percent swelling of these samples. TEM image of the prepared Ag-NPs depicts that
      the particle size of that nano-particles was <13nm. Furthermore, the prepared
      dressing surface was characterized via scanning electron microscope. The EDX of
      Ag NPs loaded dressings confirmed the presence of Ag NPs onto such dressings with
      Ag - content of 0.24% (w/w). The thermogravimetric analysis assured that the
      prepared dressings based on quaternized NWC fabric have higher thermal stability
      than the un-quaternized form.

PMID- 29596935
TI  - Inhibition of amyloid fibril formation of lysozyme by ascorbic acid and a
      probable mechanism of action.
AB  - Amyloid fibrillation of proteins and polypeptides and their deposition in cells
      and tissues is associated with a number of pathological states collectively known
      as amyloid disorders. Inhibition of protein misfolding and aggregation is thus of
      utmost importance in the prevention and treatment of such diseases. There is a
      growing interest in identification of small molecules that can bind to native
      monomeric proteins or their partially unfolded states, thereby stabilizing them
      and preventing or delaying them from undergoing amyloid fibril formation. Here we
      report the inhibitory effect of ascorbic acid, an essential dietary component
      richly present in many natural food items, on the amyloid fibrillation of hen egg
      white lysozyme, a model protein for amyloid formation. The effect was dose
      dependent with more than 80% inhibition occurring even at only a five-fold molar
      excess of ascorbic acid. TEM images show complete absence of fibrils in the
      presence of ascorbic acid. From our spectroscopic and computational
      characterization of ascorbic acid binding to HEWL, we propose that ascorbic acid
      binds to the aggregation prone beta domain of HEWL, stabilizes the partially
      unfolded conformation and prevents further conformational changes leading to
      fibrillation. Hence ascorbic acid has a great therapeutic potential for amyloid
      disorders.

PMID- 29596936
TI  - Tuning lysozyme nanofibers dimensions using deep eutectic solvents for improved
      reinforcement ability.
AB  - Deep eutectic solvents (DESs), a novel generation of solvents, have recently been
      described as efficient and timesaving fibrillation agents for proteins. In this
      context, the present work aims at assessing the effect of the hydrogen bond donor
      (HBD) of cholinium chloride ([Ch]Cl):carboxylic acid based DESs on the dimensions
      (length and width) of lysozyme nanofibers (LNFs). Mono-, di- and tri-carboxylic
      acids (acetic, lactic, levulinic, malic and citric acids) were used to prepare
      different DES formulations, which were successfully used on the fibrillation of
      lysozyme. The results showed that the carboxylic acid (i.e. the HBD) plays an
      important role on the fibrillation efficiency and on the length of the ensuing
      LNFs with aspect-ratios always higher than those obtained by fibrillation with
      [Ch]Cl. The longest LNFs were obtained using lactic acid as the HBD with an
      average length of 1004 +/- 334 nm and width of 31.8 +/- 6.8 nm, and thus an
      aspect-ratio of ca. 32. The potential of these protein nanofibers as reinforcing
      additives was evaluated by preparing pullulan (PL)-based nanocomposite films
      containing 5% LNFs with different aspect-ratios, resulting in highly homogenous
      and transparent films with improved mechanical performance.

PMID- 29596937
TI  - Insights into the molecular interaction between sucrose and alpha-chymotrypsin.
AB  - One of the most important purposes of enzyme engineering is to increase the
      thermal and kinetic stability of enzymes, which is an important factor for using
      enzymes in industry. The purpose of the present study is to achieve a higher
      thermal stability of alpha-chymotrypsin (alpha-Chy) by modification of the
      solvent environment. The influence of sucrose was investigated using thermal
      denaturation analysis, fluorescence spectroscopy, circular dichroism, molecular
      docking and molecular dynamics (MD) simulations. The results point to the effect
      of sucrose in enhancing the alpha-Chy stability. Fluorescence spectroscopy
      revealed one binding site that is dominated by static quenching. Molecular
      docking and MD simulation results indicate that hydrogen bonding and van der
      Waals forces play a major role in stabilizing the complex. Tm of this complex was
      enhanced due to the higher H-bond formation and the lower surface hydrophobicity
      after sucrose modification. The results show the ability of sucrose in protecting
      the native structural conformation of alpha-Chy. Sucrose was preferentially
      excluded from the surface of alpha-Chy which is explained by the higher tendency
      of water toward favorable interactions with the functional groups of alpha-Chy
      than with sucrose.

PMID- 29596938
TI  - Blockade of TNF receptor superfamily 1 (TNFR1)-dependent and TNFR1-independent
      cell death is crucial for normal epidermal differentiation.
AB  - BACKGROUND: A delicate balance between cell death and keratinocyte proliferation
      is crucial for normal skin development. Previous studies have reported that
      cellular FLICE (FADD-like ICE)-inhibitory protein plays a crucial role in
      prevention of keratinocytes from TNF-alpha-dependent apoptosis and blocking of
      dermatitis. However, a role for cellular FLICE-inhibitory protein in TNF-alpha
      independent cell death remains unclear. OBJECTIVE: We investigated contribution
      of TNF-alpha-dependent and TNF-alpha-independent signals to the development of
      dermatitis in epidermis-specific Cflar-deficient (CflarE-KO) mice. METHODS: We
      examined the histology and expression of epidermal differentiation markers and
      inflammatory cytokines in the skin of CflarE-KO;Tnfrsf1a+/- and CflarE
      KO;Tnfrsf1a-/- mice. Mice were treated with neutralizing antibodies against Fas
      ligand and TNF-related apoptosis-inducing ligand to block TNF-alpha-independent
      cell death of CflarE-KO;Tnfrsf1a-/- mice. RESULTS: CflarE-KO;Tnfrsf1a-/- mice
      were born but experienced severe dermatitis and succumbed soon after birth.
      CflarE-KO;Tnfrsf1a+/- mice exhibited embryonic lethality caused by massive
      keratinocyte apoptosis. Although keratinocytes from CflarE-KO;Tnfrsf1a-/- mice
      still died of apoptosis, neutralizing antibodies against Fas ligand and TNF
      related apoptosis-inducing ligand substantially prolonged survival of CflarE
      KO;Tnfrsf1a-/- mice. Expression of inflammatory cytokines, such as Il6 and Il17a
      was increased; conversely, expression of epidermal differentiation markers was
      severely downregulated in the skin of CflarE-KO;Tnfrsf1a-/- mice. Treatment of
      primary keratinocytes with IL-6 and, to a lesser extent, IL-17A suppressed
      expression of epidermal differentiation markers. CONCLUSION: TNF receptor
      superfamily 1 (TNFR1)-dependent or TNFR1-independent apoptosis of keratinocytes
      promotes inflammatory cytokine production, which subsequently blocks epidermal
      differentiation. Thus blockade of both TNFR1-dependent and TNFR1-independent cell
      death might be an alternative strategy to treat skin diseases when treatment with
      anti-TNF-alpha antibody alone is not sufficient.

PMID- 29596939
TI  - Immune checkpoint blockade therapy.
AB  - Immune checkpoints are accessory molecules that either promote or inhibit T-cell
      activation. Two inhibitory molecules, cytotoxic T-lymphocyte antigen 4 (CTLA-4)
      and programmed cell death protein 1 (PD-1), got high attention, as inhibition of
      CTLA-4 or PD-1 signaling provides the first immune therapy that significantly
      improves the survival of patients with metastatic solid cancers. Inhibition of
      CTLA-4 or PD-1 was first studied in and approved for patients with metastatic
      melanoma. Blocking immune checkpoints is also efficient in non-small-cell lung
      cancer, renal cell cancers, hypermutated gastrointestinal cancers, and others.
      Immune responses, whether directed against infections or against tumors, are
      divided into 2 phases: an initiation phase and an activation phase, where the
      immune system recognizes a danger signal and becomes activated by innate signals
      to fight the danger. This reaction is fundamental for the control of infections
      and cancer, but needs to be turned off once the danger is controlled, because
      persistence of this activation ultimately causes severe tissue damage. Therefore,
      each activation of the immune system is followed by a termination phase, where
      endogenous immune suppressor molecules arrest immune responses to prevent harmful
      damage. In the case of cancer immune therapies, therapeutic approaches
      classically enhanced the initiation and activation of immune responses to
      increase the emergence and the efficacy of cytotoxic T lymphocytes (CTL) against
      cancers. In sharp contrast, immune checkpoint blockade focuses on the termination
      of immune responses by inhibiting immune suppressor molecules. It thus prevents
      the termination of immune responses or even awakes those CTLs that became
      exhausted during an immune response. Therefore, blocking negatively regulating
      immune checkpoints restores the capacity of exhausted CTL to kill the cancer they
      infiltrate. In addition, they drive surviving cancer cells into a still poorly
      defined state of dormancy. As the therapy also awakes self-reactive CTL, one
      downside of the therapy is the induction of organ-specific autoimmune diseases.
      The second downside is the exorbitant drug price that withdraws patients in need
      from a therapy that was developed by academic research, which impairs further
      academic treatment development and financially charges the public health system.

PMID- 29596940
TI  - Long-term outcomes associated with triple-goal achievement in patients with type
      2 diabetes mellitus (T2DM).
AB  - AIMS: This study was designed to compare the risk of long-term health outcomes,
      including microvascular, macrovascular complications and mortality, across 4
      cohorts: triple-goal, dual-goal, single-goal, and no-goal achievers. METHODS: A
      retrospective cohort of 53,120 patients with T2DM were identified (97.51% male,
      61.49% whites) from the Veterans Affairs (VA) electronic medical records VISN 16
      data warehouse (2004-2010). Propensity score weight (PSW) was used to balance
      demographic characteristics and complication history at baseline. The PSW
      adjusted hazard ratios (aHR) from Cox proportional hazard models were used to
      compare complications and all-cause mortality over an average of 4 years of
      follow-up. RESULTS: At baseline, 25.43% (13,507) patients achieved triple-goal,
      while 41.36% (21,972) and 26.37% (14,010) patients achieved dual-goal and single
      goal, respectively. During the follow-up period, triple-goal achievement was
      associated with risk reductions of complications and all-cause mortality when
      compared to all other groups of achieving dual or single-goal. Across different
      combinations of dual-goal achievement, the cohort with LDL-C goal achievement had
      lower risk of complication events and mortality, compared to those that achieved
      other goals but failed to reach LDL-C goal. CONCLUSIONS: Achievement of triple
      goal was associated with better health outcomes among veterans with T2DM compared
      to those that did not, while LDL-C has more weight of influence. Multi-faceted
      treatment strategies targeting hypertension, hyperglycemia and hyperlipidemia may
      improve health outcome in veterans with T2DM.

PMID- 29596941
TI  - Prevalence of type 2 diabetes and prediabetes in the Faroe Islands.
AB  - AIMS: To determine the prevalence of type 2 diabetes mellitus and prediabetes
      among the population aged 40-74 years in the Faroe Islands. METHODS: This
      population-based cross-sectional survey, conducted between 2011 and 2012, invited
      2186 randomly selected individuals (corresponding to 11.1% of the entire
      population aged 40-74 years). Subjects were screened using finger capillary blood
      for glycosylated hemoglobin, type A1c, non-fasting random plasma glucose, fasting
      plasma glucose followed by oral glucose tolerance test. The test was based on an
      algorithm that accounts for screening, diagnostic and confirmatory steps.
      Anthropometric measures and a questionnaire including medical history,
      medication, hereditary conditions, and food intake were included. RESULTS: The
      study included 1772 participants. Of the 1772, 169 (9.5%) had type 2 diabetes
      mellitus (3.0% of which were diagnosed upon study inclusion), thus 31.4% of
      subjects with diabetes were undiagnosed at the time of examination. A total of
      271 (15.3%) had prediabetes. Diabetes was more prevalent among men, significantly
      from age >=60 years. Women had lower mean fasting plasma glucose concentrations
      and men had lower values for 2-h plasma glucose. Predictors associated with
      diabetes mellitus included obesity (BMI >= 30), abnormal waist/hip ratio, history
      of hypertension or cardiovascular attack and family history of diabetes mellitus
      and leisure activity. CONCLUSIONS: The prevalences of diabetes and prediabetes
      increased with age and were more frequent among men. The detected prevalence in
      the Faroe Islands was slightly higher than other Nordic countries.

PMID- 29596942
TI  - Diabetes in the Bedouin population in the Israeli Negev - An update 2017.
AB  - AIMS: The Bedouins are an Arab population living in Israel severely impacted by
      diabetes and obesity. The aim of this research was to update the prevalence of
      diabetes among Bedouins in the Negev and to observe differences in this
      population in comparison with non-Bedouins in Israel. METHODS: A cross-sectional
      study was performed using the Clalit Health Services database. Diabetes
      prevalence among Bedouins was compared with non-Arabs and non-Bedouin Arabs in
      Israel. Differences in sexes and among Bedouins living in planned cities and
      unrecognized villages were observed. RESULTS: The age-adjusted prevalence of
      diabetes was 12.3% in the Bedouin population versus 8.2% in the non-Arab
      population in southern Israel (p < 0.0001). Diabetes prevalence among Bedouins
      and all Arabs in Israel was similar (12.0%). In all of Israel, age-adjusted
      diabetes prevalence was 8.8% for men and 7.5% in women (p < 0.0001) compared to
      12.0% for men and 12.5% for women in the Bedouin population (p = 0.0008). In the
      Bedouin population in planned cities, age-adjusted diabetes prevalence was 12.5%
      versus 10.5% in the Bedouin population in unrecognized villages (p < 0.0001).
      CONCLUSIONS: This study shows that the prevalence of diabetes among Bedouins is
      higher than non-Bedouins in Israel. Increasing urbanization of the Bedouin
      population with their higher diabetes prevalence indicates the need for increased
      medical intervention as well as continuing investigation into the causes.

PMID- 29596943
TI  - The Berlin Declaration: A call to action to improve early actions related to type
      2 diabetes. How can specialist care help?
AB  - Diabetes is a major global epidemic and places a huge burden on healthcare
      systems worldwide. The complications of type 2 diabetes (T2D) and related
      hospitalizations are major contributors to this burden, and there is strong
      evidence that the risk for these can be reduced by early action to identify and
      prevent progression of people at high risk of T2D and ensure tight glycemic
      control in those with established disease. In response to this, the Berlin
      Declaration was developed by four working groups of experts and ratified by
      healthcare professionals from 38 countries. Its aim is to act as a global call to
      action for early intervention in diabetes, in addition to providing short-,
      medium- and long-term targets that should be relevant to all nations. The Berlin
      Declaration focuses on four aspects of early action, and proposes actionable
      policies relating to each aspect: early detection, prevention, early control and
      early access to the right interventions. In addition, a number of treatment
      targets are proposed to provide goals for these policies. To ensure that the
      suggested policies are enacted in the most effective manner, the support of
      specialist care professionals is considered essential.

PMID- 29596944
TI  - Postpartum risk of diabetes and predictive factors for glucose intolerance in
      East Asian women with gestational diabetes.
AB  - AIMS: Women with a history of gestational diabetes mellitus (GDM) are likely to
      develop postpartum diabetes mellitus (DM). We examined women in the early stages
      of pregnancy who were at high risk of postpartum DM progression to establish a
      follow-up method for early detection. METHODS: We performed the oral glucose
      tolerance test (OGTT) and identified predictive factors for postpartum impaired
      glucose tolerance (IGT) or DM in 77 women after GDM, for 2 years after delivery,
      retrospectively. Cutoff values for each factor were determined. We classified
      these women with GDM into four groups using these predictive factors and
      evaluated postpartum glucose intolerance (GI) in each group. RESULTS: In total,
      44.1% of the women with a GDM history had developed postpartum GI within 2 years.
      We determined three risk factors for postpartum GI: elevated glucose level 120
      min after a 75-g OGTT (Glu120), elevated glycated hemoglobin (HbA1c) level at
      diagnosis, and perinatal complications. The cutoff Glu120 and the HbA1c level
      were 155 mg/dl and 5.3% (34 mmol/mol), respectively. Type 2 DM developed in 53.8%
      of women, and IGT developed in 38.5% of women within 2 years in groups with high
      Glu120 and high HbA1c. CONCLUSIONS: High-risk groups require careful follow-up
      observation.

PMID- 29596945
TI  - Association between diabetic peripheral neuropathy and heart rate variability in
      subjects with type 2 diabetes.
AB  - AIM: This study evaluated the association of Heart rate variability (HRV)
      measurements with diabetic peripheral neuropathy (DPN) in patients with type 2
      diabetes. METHODS: This study included 102 Korean subjects with type 2 diabetes.
      The Michigan neuropathy screening instrument (MNSI) questionnaire score, the MNSI
      examination score (MNSIES) and the total symptom score were examined for DPN
      evaluation. Noninvasive HRV measurements were performed using photoelectric
      plethysmography. Patients with a MNSIES > 2 were considered to have DPN. RESULTS:
      The MNSIES showed significant negative associations with the high frequency (HF)
      (r = -0.212, p = 0.033) and low frequency (LF) (r = -0.286, p = 0.004) powers.
      Multiple linear regression analysis revealed that only HF power maintained a
      significant negative association with the MNSIES (beta = -0.184; 95% CI -0.365 to
      -0.003; p = 0.047), after controlling for significant related confounders, with
      HRV parameters in male patients with type 2 diabetes. The HF (p = 0.010) and LF
      (p = 0.025) powers differed significantly between male patients without and those
      with DPN according to the MNSIES. CONCLUSIONS: This study revealed a negative
      association of DPN, as assessed by the MNSIES, with HF power in male patients
      with type 2 diabetes. DPN defined by foot examination was predictive of cardiac
      autonomic neuropathy.

PMID- 29596946
TI  - Genome-wide DNA methylation profiling in infants born to gestational diabetes
      mellitus.
AB  - BACKGROUND: Offspring exposed to gestational diabetes mellitus (GDM) are at a
      high risk for metabolic diseases. The mechanisms behind the association between
      offspring exposed to GDM in utero and an increased risk of health consequences
      later in life remain unclear. The aim of this study was to clarify the changes in
      methylation levels in the foetuses of women with GDM and to explore the possible
      mechanisms linking maternal GDM with a high risk of metabolic diseases in
      offspring later in life. METHODS: A genome-wide comparative methylome analysis on
      the umbilical cord blood of infants born to 30 women with GDM and 33 women with
      normal pregnancy was performed using Infinium HumanMethylation 450 BeadChip
      assays. A quantitative methylation analysis of 18 CpG dinucleotides was verified
      in the validation umbilical cord blood samples from 102 newborns exposed to GDM
      and 103 newborns who experienced normal pregnancy by MassARRAY EpiTYPER. RESULTS:
      A total of 4485 differentially methylated sites (DMSs), including 2150
      hypermethylated sites and 2335 hypomethylated sites, with a mean beta-value
      difference of >0.05, were identified by the 450k array. Good agreement was
      observed between the massarray validation data and the 450k array data (R2 >
      0.99; P < 0.0001). Thirty-seven CpGs (representing 20 genes) with a beta-value
      difference of > 0.15 between the GDM and healthy groups were identified and
      showed potential as clinical biomarkers for GDM. "hsa04940: Type I diabetes
      mellitus" was the most significant Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway, with a P-value = 3.20E-07 and 1.36E-02 in the hypermethylated and
      hypomethylated genepathway enrichment analyses, respectively. In the Gene
      Ontology (GO) pathway analyses, immune MHC (major histocompatibility complex)
      related pathways and neuron development-related pathways were significantly
      enriched. CONCLUSIONS: Our results suggest that GDM has epigenetic effects on
      genes that are preferentially involved in the Type I diabetes mellitus pathway,
      immune MHC-related pathways and neuron development-related pathways, with
      consequences on fetal growth and development, and provide supportive evidence
      that DNA methylation is involved in fetal metabolic programming.

PMID- 29596947
TI  - FIGO analysis of research priorities in hyperglycemia in pregnancy.
AB  - Hyperglycemia in pregnancy (HIP) is recognized as a major underlying cause of
      pregnancy complications and a contributing cause to health risks throughout the
      subsequent life of both mothers and babies, with amplification of the global
      epidemic of non-communicable diseases. Although some aspects of these
      associations are well described, detailed understanding of basic pathophysiologic
      mechanisms is lacking. Improved fundamental scientific knowledge must be
      developed to allow logical strategies for prevention and treatment. During
      pregnancy, much work is required to replace current empirical approaches to
      diagnosis and treatment of HIP with evidence based protocols, pragmatically
      adapted to differing health care and health economic contexts. Further, a life
      cycle approach to HIP, the risk of immediate pregnancy complications and later
      health risks to mother and baby must be developed and implemented across a wide
      range of health care environments. This document aims to outline key focus areas
      for further basic, epidemiologic, clinical and implementation research in this
      important area.

PMID- 29596948
TI  - What is the best strategy on detection of cornea neuropathy in people with
      diabetes? Recent advances in potential measurements.
AB  - There are well-acknowledged clinical or pre-clinical measurements concerning
      diabetic peripheral neuropathy (DPN). The current gold standard for diagnosis of
      diabetic peripheral neuropathy is nerve conduction suitable for detecting large
      nerve fiber function and intraepidermal nerve fiber density assessment for small
      fiber damage evaluation [2]. The lack of a sensitive, non-invasive, and
      repeatable endpoint to measure changes in small nerve fibers is a major factor
      holding back clinical trials for the treatment of diabetic peripheral neuropathy.
      As cornea is the most densely innerved tissue, assessing corneal nerves'
      structure and function will be promising to predict and assess the degree of DPN.
      In the diabetic micro-environment, damaged corneal nerves lead to decreased
      corneal sensitivity, both of which resulting in abnormal tear function. According
      to this theory, the measurements of nerve structure, corneal sensitivity, tear
      secretion and tear components, to some extent, can reveal and assess the state of
      corneal neuropathy. This review focuses on summarizing the knowledge of the
      latest detective methods of diabetic corneal neuropathy, popular in use or
      possible to further in study and be applied into clinical practice.

PMID- 29596949
TI  - Epidemiological dimensions of the association between type 2 diabetes and cancer:
      A review of observational studies.
AB  - Type 2 diabetes (T2D) is a major cause of complications and death in many
      countries. The possible causal relation between T2D and cancer has been the aim
      of many research investigations. In view of the importance of the topic we
      carried out a narrative review of observational studies to summarize the
      available evidence of the association between T2D and cancer. To deal with the
      problem of abundance of published studies, we reviewed up to December 2017, the
      literature of meta-analyses of observational studies first, then we reviewed
      cohort studies not reported in meta-analyses because of more recent publication.
      We found that the association of T2D with risk of colorectal cancer was robust,
      whereas the evidence of the associations with other cancer sites was lower. Some
      of the observed associations could be overestimated, due to publication bias,
      unmeasured confounders (such as obesity) and surveillance bias. In conclusion a
      probable causal association of T2D with risk of colorectal cancer was confirmed.
      A possible causal association with pancreatic, endometrial, hepatocellular and
      gallbladder carcinoma was also found. Substantial uncertainty exists for other
      cancer sites.

PMID- 29596950
TI  - One-year effects of a group-based lifestyle intervention in adults with type 2
      diabetes: A randomized encouragement trial.
AB  - AIMS: To estimate the real-world effects of offering a group-based lifestyle
      intervention (GLI) to adults with diabetes. METHODS: This randomized
      encouragement trial included adult primary care patients in metropolitan Chicago
      with type 2 diabetes and body mass index >=24 kg/m2. Participants were randomized
      to standard care (brief dietary and lifestyle counseling) or standard care plus
      being encouraged, but not required, to participate in a free-of-charge GLI
      offered by the YMCA. The GLI was a group-based adaptation of the Look AHEAD
      lifestyle intervention. RESULTS: Of 331 participants, 167 were randomized to
      standard care and 164 to the GLI encouragement arm. About one third of
      participants were non-Hispanic White (34.4%). In the GLI arm, 75 (45.7%) attended
      >=1 GLI visits. In the primary intention-to-treat analysis, the effect of GLI
      encouragement was 0.95% weight loss at six months (95% confidence interval [CI],
      0.13-1.77%; P = 0.02), and 1.20% weight loss at 12 months (95% CI, 0.05-2.36%; P
      = 0.04). At 12 months, there was a 0.30% (3.3 mmol/mol) reduction in hemoglobin
      A1c, but this result did not achieve statistical significance (P = 0.054). In
      instrumental variable analysis estimating effects among the subgroup of
      participants who attended any GLI visits, the effect of GLI attendance was 2.30%
      weight loss at six months (95% CI, 0.30-4.30%; P = 0.02), and 2.07% weight loss
      at 12 months (95% CI, 0.25-3.88%; P = 0.02). We detected no significant blood
      pressure or cholesterol effects. CONCLUSIONS: Among adults with type 2 diabetes,
      a group-based lifestyle intervention in a community-based setting achieved modest
      weight loss at 6 and 12 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier NCT01435603.

PMID- 29596952
TI  - Diabetologists and Oncologists attitudes towards treating diabetes in the
      oncologic patient: Insights from an exploratory survey.
AB  - AIMS: Diabetes and cancer frequently coexist in the same subject, often having
      relevant effects on the management and prognosis of the oncologic patient.
      However, existing guidelines do not deal with many clinical issues in this
      setting appropriately. In evaluating the opinions of Diabetologists and
      Oncologists dealing with diabetes care in people with cancer, the Italian
      Association of Diabetologists (AMD) promoted a dedicated exploratory survey.
      METHODS: The survey was carried out through the web or handily delivered printed
      copies between October 2014 and April 2015, in Italy. It was composed of 27
      questions intended to gather information on the characteristics of participants
      and to examine their clinical habits in this context, and participation was
      totally free and anonymous. RESULTS: A total of 252 physicians participated in
      the survey. Diabetologists accounted for 51.1% of respondents. According to
      survey results, in spite of the presence of diabetes (or diabetic complications)
      worsening the outcome of cancer treatments, the counseling or intervention of a
      Diabetologist was only required for less than two-thirds of hospitalized
      patients. For subjects with a life expectancy of months, 80% of specialists
      considered a glycemic target of 120-250 mg/dL optimal whereas Oncologists were
      more likely to consider a range of 180-360 mg/dL for patients with a shorter life
      expectancy. Furthermore, 1 participant out of 3 indicated 1-4 measurements/day as
      the most appropriate frequency for blood glucose monitoring including in the
      palliative setting. Insulin was the therapy of choice for the majority of
      respondents albeit with different routes of administration. CONCLUSIONS: This
      survey provides interesting preliminary data that could help facilitate and
      optimize the management of patients with cancer and diabetes, promoting the
      delivery of an organic answer to fragmented assistance, to potentially
      inappropriate behaviors, and to a tailored therapy in a context of particular
      clinical fragility.

PMID- 29596951
TI  - A randomized controlled trial to compare the effects of sulphonylurea gliclazide
      MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic
      variability and control measured by continuous glucose monitoring (CGM) in
      Brazilian women with type 2 diabetes.
AB  - AIMS: This study aims to evaluate whether there is a difference between the
      effects of vildagliptin and gliclazide MR (modified release) on glycemic
      variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous
      glucose monitoring (CGM). METHODS: An open-label, randomized study was conducted
      in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg
      vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV
      indices calculation were performed at baseline and after 24 weeks. RESULTS: In
      total, 42 patients (age: 61.9 +/- 5.9 years, baseline glycated hemoglobin
      (HbA1c): 7.3 +/- 0.56) were selected and 37 completed the 24-week protocol.
      Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of
      glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference
      between the groups did not reach statistical significance. Vildagliptin also
      significantly decreased the standard deviation of the mean glucose (SD) and the
      mean of the daily differences (MODD) (p = 0.007 and 0.030). CONCLUSIONS:
      Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM
      after 24 weeks of treatment. Further studies are required to attest differences
      between vildagliptin and gliclazide MR regarding glycemic variability.

PMID- 29596953
TI  - Measuring the reliability and validity of the Greek edition of the Diabetes
      Quality of Life Brief Clinical Inventory.
AB  - BACKGROUND: The present study focuses on studying the validity and reliability of
      the Greek edition of DQOL-BCI. DQOL-BCI includes 15 questions-elements that are
      evaluated on a 5-grade scale like Likert and two general form-shapes. METHODS:
      The translation process was conducted in conformity with the guidelines of
      EuroQol group. A non-random sample of 65 people-patients diagnosed with diabetes
      I and II was selected. The questionnaire that was used to collect the data was
      the translated version of DQOL-BCI, and included the demographic characteristics
      of the interviewees. The content validity of DQOL-BCI was re-examined from a team
      of five experts (expert panel) for qualitative and quantitative performance. The
      completion of the questionnaire was done via a personal interview. RESULTS: The
      sample consisted of 58 people (35 men and 23 women, 59.9 +/- 10.9 years). The
      translation of the questionnaire was found appropriate in accordance to the
      peculiarities of the Greek language and culture. The largest deviation of values
      is observed in QOL1 (1.71) in comparison to QOL6 (2.98). The difference between
      the standard deviations is close to 0.6. The statistics results of the tests
      showed satisfactory content validity and high construct validity, while the high
      values for Cronbach alpha index (0.95) reveal high reliability and internal
      consistency. CONCLUSIONS: The Greek version of DQOL-BCI has acceptable
      psychometric properties and appears to demonstrate high internal reliability and
      satisfactory construct validity, which allows its use as an important tool in
      evaluating the quality of life of diabetic patients in relation to their health.

PMID- 29596955
TI  - Alterations of complex mismatch negativity (cMMN) elicited by a two-tone pattern
      paradigm in early-phase psychosis.
AB  - The mismatch negativity (MMN) is a component of the event-related potential (ERP)
      elicited by a change in auditory stimulation (e.g., the occurrence of a deviant
      sound that violates the rules or regularities of the preceding stimulus sequence)
      regardless of whether one is attending to the change or not. As such, the MMN
      provides a useful index of pre-attentive cognition. While decreases in MMN
      amplitude are robustly observed in chronic schizophrenia, these deficits are less
      consistently present at the early phase of the illness. The current study
      utilizes a two-tone pattern paradigm that requires more complex computations than
      typical oddball stimulus presentations, which may be more appropriate for
      elucidating MMN deficits in an early phase psychosis (EP) sample. The stimuli
      were a standard sequence consisting of two alternating tones with different tonal
      frequencies (eg. ABABAB...), with MMN-eliciting pattern violations created by
      repetitions of either the A or the B tone. EEG recordings of 15 EP participants
      and 12 healthy controls (HCs) were collected. While no between-group differences
      were observed, MMN amplitudes in the EP group were correlated with positive and
      negative psychosis symptom scores. Follow-up analysis stratifying EP participants
      according to illness duration showed a reduced MMN amplitude in EP participants
      with a longer (2+ years) duration of illness, but not in EP participants who were
      within the first year of illness. These findings suggest a two-tone pattern
      paradigm may be useful in characterizing MMN-indexed cortical impairment later in
      the early phase of the illness, but not at first episode.

PMID- 29596954
TI  - Usefulness of glycated albumin as a biomarker for glucose control and prognostic
      factor in chronic kidney disease patients on dialysis (CKD-G5D).
AB  - In chronic kidney disease patients on dialysis (CKD-G5D) accurate assessment of
      glycemic control is vital to improve their outcome and survival. The best
      glycemic marker for glucose control in these patients is still debated because
      several clinical and pharmacological factors may affect the ability of the
      available biomarkers to reflect the patient's glycemic status properly. This
      review discusses the role of glycated albumin (GA) both as a biomarker for
      glucose control and as a prognostic factor in CKD-G5D; it also looks at the pros
      and cons of GA in comparison to the other markers and its usefulness in
      hemodialysis and peritoneal dialysis.

PMID- 29596956
TI  - Individual differences in infants' neural responses to their peers' cry and
      laughter.
AB  - Infants' ability to process others' emotional expressions is fundamental for
      their social development. While infants' processing of emotions expressed by
      faces and speech has been more extensively investigated, less is known about how
      infants process non-verbal vocalizations of emotions. Here, we recorded frontal
      N100, P200, and LPC event-related potentials (ERPs) from 8-month-old infants
      listening to sounds of other infants crying, laughing, and coughing. Infants'
      temperament was measured via parental report. Results showed that processing of
      emotional information from non-verbal vocalizations was associated with more
      negative N100 and greater LPC amplitudes for peer's crying sounds relative to
      positive and neutral sounds. Temperament was further related to the N100, P200,
      and LPC difference scores between conditions. One important finding was that
      infants with improved ability to regulate arousal exhibited increased sustained
      processing of peers' cry sounds compared to both laughter and cough sounds. These
      results emphasize the relevance of considering the temperamental characteristics
      in understanding the development of infant emotion information processing, as
      well as for formulating comprehensive theoretical models of typical and atypical
      social development.

PMID- 29596957
TI  - Suppression of no-longer relevant information in Working Memory: An alpha-power
      related mechanism?
AB  - Selective attention can enhance Working Memory (WM) performance by selecting
      relevant information, while preventing distracting items from encoding or from
      further maintenance. Alpha oscillatory modulations are a correlate of
      visuospatial attention. Specifically, an enhancement of alpha power is observed
      in the ipsilateral posterior cortex to the locus of attention, along with a
      suppression in the contralateral hemisphere. An influential model proposes that
      the alpha enhancement is functionally related to the suppression of information.
      However, whether ipsilateral alpha power represents a mechanism through which no
      longer relevant WM representations are inhibited has yet not been explored. Here
      we examined whether the amount of distractors to be suppressed during WM
      maintenance is functionally related to alpha power lateralized activity. We
      measure EEG activity while participants (N = 36) performed a retro-cue task in
      which the WM load was varied across the relevant/irrelevant post-cue hemifield.
      We found that alpha activity was lateralized respect to the locus of attention,
      but did not track post-cue irrelevant load. Additionally, non-lateralized alpha
      activity increased with post-cue relevant load. We propose that alpha
      lateralization associated to retro-cuing might be related to a general orienting
      mechanism toward relevant representation.

PMID- 29596958
TI  - Transfer of plasmid into the pentose-fermenting yeast Pachysolen tannophilus.
AB  - The pentose-fermenting yeast Pachysolen tannophilus can convert glucose and
      xylose in lignocellulosic hydrolysates to ethanol. However, it performs poorly in
      industrially relevant lignocellulosic hydrolysates containing mixed sugars and
      inhibitors. Efforts have been directed at improving the performance of this yeast
      to enable efficient lignocellulosic biomass conversion. While some successes have
      been reported using random mutagenesis and/or hybridization-based approaches,
      further genetic improvement of this yeast is hampered by the lack of efficient
      gene transfer methods as well as limited genetic information to guide further
      construction of robust strains of P. tannophilus. In this study, we aimed to
      address this short-coming by establishing the optimal conditions needed for
      efficient gene transfer into P. tannophilus. We ascertained that plasmids can be
      transferred into P. tannophilus through trans-kingdom conjugation or lithium
      acetate (LiAc) transformation. The efficiency of plasmid YEp13 (2-micron, LEU2)
      transferred into a P. tannophilus leucine auxotroph (Leu-) reached as high as
      1.93 * 10-2 transconjugants per input recipient and 3.25 * 104 transformants per
      MUg plasmid DNA through trans-kingdom conjugation and transformation,
      respectively. In trans-kingdom conjugation, the number of recipient P.
      tannophilus cells played an important role, while the ratio of donor (Escherichia
      coli) to recipient cells was less important. For efficient transformation in P.
      tannophilus, the use of PEG 3350 was essential, as no transformants were obtained
      in its absence. The transformation efficiency increased with the addition of
      single-stranded carrier DNA and incubation at 30  degrees C for >60 min. Plasmids
      with different replication origins or 2-micron plasmids with different CUG codon
      optimized antibiotic resistance markers were unable to transform P. tannophilus
      under our experimental conditions. The results are of interest in the genetic
      manipulation and improvement of P. tannophilus.

PMID- 29596959
TI  - Two efficient methods for isolation of high-quality genomic DNA from
      entomopathogenic fungi.
AB  - Conventional and commercial methods for isolation of nucleic acids are available
      for fungal samples including entomopathogenic fungi (EPF). However, there is not
      a unique optimal method for all organisms. The cell wall structure and the wide
      range of secondary metabolites of EPF can broadly interfere with the efficiency
      of the DNA extraction protocol. This study compares three commercial protocols:
      DNeasy(r) Plant Mini Kit (Qiagen), Wizard(r) Genomic DNA Purification Kit
      (Promega), and AxygenTM Multisource Genomic DNA Miniprep Kit (Axygen) and three
      conventional methods based on different buffers: SDS, CTAB/PVPP, and CTAB/beta
      mercaptoethanol versus three cell lysis procedures: liquid nitrogen
      homogenization and two bead-beating materials (i.e., tungsten-carbide and
      stainless-steel) for four representative species of EPF (i.e., Beauveria
      bassiana, Hirsutella citriformis, Isaria javanica, and Metarhizium anisopliae).
      Liquid nitrogen homogenization combined with DNeasy(r) Plant Mini Kit (i.e., QN)
      or SDS buffer (i.e., SN) significantly improved the yield with a good purity
      (~1.8) and high integrity (>20,000 bp) of genomic DNA in contrast with other
      methods, also, these results were better when compared with the two bead-beating
      materials. The purified DNA was evaluated by PCR-based techniques: amplification
      of translation elongation factor 1-alpha (TEF) and two highly sensitive molecular
      markers (i.e., ISSR and AFLP) with reliable and reproducible results. Despite a
      variation in yield, purity, and integrity of extracted DNA across the four
      species of EPF with the different DNA extraction methods, the SN and QN protocols
      maintained a high-quality of DNA which is required for downstream molecular
      applications.

PMID- 29596960
TI  - Improving the selection efficiency of the counter-selection marker pheS* for the
      genetic engineering of Bacillus amyloliquefaciens.
AB  - Bacillus subtilis pheS was genetically modified to obtain a counter-selection
      marker with high selection efficiency in Bacillus amyloliquefaciens. The
      application of the new replication-thermosensitive integrative vector pNZTM1,
      containing this marker, pheSBsT255S/A309G, with a two-step replacement
      recombination procedure provides an effective tool for the genetic engineering of
      industrially important Bacillus species.

PMID- 29596961
TI  - Protein restriction and cancer.
AB  - Protein restriction without malnutrition is currently an effective nutritional
      intervention known to prevent diseases and promote health span from yeast to
      human. Recently, low protein diets are reported to be associated with lowered
      cancer incidence and mortality risk of cancers in human. In murine models,
      protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1,
      amino acid metabolic programing, FGF21, and autophagy may also serve as potential
      mechanisms of protein restriction mediated cancer prevention. Together, dietary
      intervention aimed at reducing protein intake can be beneficial and has the
      potential to be widely adopted and effective in preventing and treating cancers.

PMID- 29596962
TI  - New isopimarane diterpenes and nortriterpene with cytotoxic activity from
      Ephorbia alatavica Boiss.
AB  - Three new isopimarane diterpenes and one new nor-triterpenes, along with five
      known diterpenes were isolated from the whole areal part of Ephorbia alatavica
      Boiss. The structures of the new compounds (1-4) were determined based on
      extensive spectroscopic analysis, including HR-ESIMS, 1D and 2D NMR data. A
      plausible biosynthetic pathway for new compounds (1-4) were hypothesized. All
      isolated compounds were screen for cytotoxicity activity against MCF-8, HeLa and
      A549 cell lines in vitro by MTT assay. New compound 1 and known 9 showed
      potential cytotoxic activities with IC50 values of 15.327 MUg/mL, 23.066 MUg/mL
      against MCF-8 cell lines, compound1 showed noteworthy cytotoxic activity with
      IC50 13.033 MUg/mL against A549 cancer cell line. New compounds 2, 4 and 4 showed
      moderate cytotoxic activities three human cancer lines with IC50 value around 50
      MUg/mL, which compared with positive control doxorubicin (DOX).

PMID- 29596963
TI  - The effect of interaction between EtOH dosage and exposure time on gene
      expression in DPSC.
AB  - Alcohol (EtOH) dosage and exposure time can affect gene expression. However,
      whether there exists synergistic effect is unknown. Here, we analyzed the hDPSC
      gene microarray dataset GSE57255 downloaded from Gene Expression Omnibus and
      found that the interaction between EtOH dosage and exposure time on gene
      expression are statistically significant for two probes: 201917_s_at near gene
      SLC25A36 and 217649_at near gene ZFAND5. GeneMania showed that SLC25A36 and
      ZFAND5 were related to 20 genes, three of which had alcohol-related functions.
      WebGestalt revealed that the 22 genes were enriched in 10 KEGG pathways, four of
      which are related to alcoholic diseases. We explored the possible nonlinear
      interaction effect and got 172 gene probes with significant p-values. However, no
      significantly enriched pathways based on the 172 probes were detected. Our
      analyses indicated a possible molecular mechanism that could help explain why
      alcohol consumption has both deleterious and beneficial effects on human health.

PMID- 29596964
TI  - Low bone density and fractures before and after pediatric lung transplantation.
AB  - INTRODUCTION: Children undergoing lung transplant are at risk for low bone
      mineral density (BMD) and fractures. The effect of lung transplantation on bone
      health in pediatric patients is unknown. MATERIALS AND METHODS: We performed a
      retrospective chart review of all patients ages 2-21 years who underwent lung
      transplantation at our hospital from January 2000 to January 2015. RESULTS: 51
      patients were studied. At the time of transplant evaluation, BMD Z-score was -2.2
      +/- 1.4, and 59% of patients had low BMD. BMD Z-score declined in the first year
      after treatment and returned to near-baseline by the third post-transplant year.
      Fractures occurred in 9 patients (18%) before and 15 patients (29%) after
      transplant. Bisphosphonate use was associated with improvement in BMD Z-score and
      lower mortality risk. CONCLUSIONS: Pediatric patients had a high prevalence of
      low BMD at the time of lung transplant evaluation. BMD Z-scores declined in the
      year after transplant and returned to the pre-transplant level by the third post
      transplant year while remaining below normal levels. Fractures were common at
      sites associated with significant morbidity. These findings support efforts to
      optimize bone health before and after pediatric lung transplantation, and future
      studies are needed to evaluate the role of bisphosphonates in these patients.

PMID- 29596965
TI  - Oxytocin Inhibits Corticosterone-induced Apoptosis in Primary Hippocampal
      Neurons.
AB  - Stress is an adaptive and coordinated response to endogenous or exogenous
      stressors that pose an unpleasant and aversive threat to an individual's
      homeostasis and wellbeing. Glucocorticoids, corticosterone (CORT) in rodents and
      cortisol in humans, are adrenal steroids which are released in response to
      stressful stimuli. Although they help individuals to cope with stress, their
      overexposure in animals has been implicated in hippocampal dysfunction and
      neuronal loss. Oxytocin (OT) plays an active role in adaptive stress-related
      responses and protects hippocampal synaptic plasticity and memory during stress.
      In this study, we showed that OT protects primary mouse hippocampal neurons from
      CORT-induced apoptosis. OT receptors (OTR) were expressed in primary mouse
      hippocampal neurons and glial cells. CORT induced apoptosis in hippocampal
      neurons, but had no effect on apoptosis in glial cells. OT inhibited CORT-induced
      apoptosis in primary hippocampal neurons. OT was unable to protect primary
      hippocampal neurons prepared from OTR KO mice from CORT-induced apoptosis. These
      results indicate that OT has inhibitory effects on CORT-induced neuronal death in
      primary hippocampal neurons via acting on OTR. The findings suggest a therapeutic
      potential of OT in the treatment of stress-related disorders.

PMID- 29596966
TI  - Characterization of Hit Compounds Identified from High-throughput Screening for
      their Effect on Blood-brain Barrier Integrity and Amyloid-beta Clearance: In
      Vitro and In Vivo Studies.
AB  - In Alzheimer's disease (AD) the blood-brain barrier (BBB) is compromised, thus
      therapeutic targeting of the BBB to enhance its integrity and function could be a
      unique approach to treat, slow or hold the progression of AD. Recently, we have
      developed an in vitro high-throughput screening assay to screen for compounds
      that increase the integrity of a cell-based BBB model. Results from primary
      screen identified multiple hit compounds that enhanced the monolayer integrity.
      Herein, further characterization of selected hit compounds, namely 8
      bromoguanosine cyclic monophosphate, JW74, 1,10-phenanthroline monohydrate,
      SB216763 and alpha-tocopherol was performed. Compounds were subjected to
      concentration-dependent studies to determine their EC50 and potency to enhance
      the cell-based model integrity by the Lucifer Yellow permeability and amyloid
      beta (Abeta) transport across the monolayer. The compounds demonstrated different
      EC50s to enhance the monolayer integrity ranging from 0.4 to 12.8 uM, and
      different effect on enhancing Abeta transport with highest transport observed for
      alpha-tocopherol (2.2-fold increase). Such effects were associated with increased
      levels of tight junction proteins such as claudin-5 and/or ZO-1, and Abeta major
      transport proteins LRP1 and P-glycoprotein. In vivo studies for alpha-tocopherol
      were performed in AD mouse model; consistent with the in vitro results alpha
      tocopherol significantly increased BBB integrity measured by IgG extravasation,
      and reduced brain Abeta levels. In conclusion, findings support our developed
      cell-based BBB model as a functional predictive in vivo tool to select hit
      compounds, and suggest that enhancing BBB tightness and function has the
      potential to reduce Abeta pathology associated with AD.

PMID- 29596967
TI  - Parabens and their effects on the endocrine system.
AB  - Preservatives (ingredients which inhibit growth of microorganisms) are used to
      prolong shelf life of various foods, cosmetics, and pharmaceutical products.
      Parabens are one of the most popular preservatives used in the aforementioned
      products and is currently being used worldwide. Parabens are easily absorbed by
      the human body. Thus, it is important to discuss about their safety with respect
      to human physiology. In view of the current literature, which classifies parabens
      as a group of endocrine disrupting chemicals (EDCs), it seems that the precise
      assessment of their influence on the human endocrine system is particularly
      important. Disruption of the endocrine homoeostasis might lead to
      multidirectional implications causing disruption of fitness and functions of the
      body. Therefore, in this review article, we aimed to summarize the current
      literature on properties, occurrence, and metabolism of parabens as well as to
      present recent progress in knowledge about their influence on the human endocrine
      system.

PMID- 29596969
TI  - Global gene expression analysis indicates that small luteal cells are involved in
      extracellular matrix modulation and immune cell recruitment in the bovine corpus
      luteum.
AB  - Genome wide mRNA expression analysis of small and large luteal cells, isolated
      from the mature staged corpora lutea (CL), was not performed in any species. In
      the current study, we have isolated bovine small and large luteal cells from mid
      cycle (day 10-11) animals and characterized their transcriptomes using
      "GeneChipTM Bovine Gene 1.0 ST Arrays". A total of 1276 genes were identified to
      be differentially expressed between small and large luteal cells. Data evaluation
      revealed that novel functions, extracellular matrix synthesis and immune cell
      recruitment, were enriched in small luteal cells. On contrary, functions
      regarding the regulation of folliculogenesis, luteal regression, fatty acid and
      branched chain amino acid metabolism were differentially enriched in large luteal
      cells. Overall, the current data offer a first and detailed insight into the
      functional roles of small and large luteal cells in the mature bovine corpus
      luteum.

PMID- 29596968
TI  - Sequential gene regulatory events leading to glucocorticoid-evoked apoptosis of
      CEM human leukemic cells:interactions of MAPK, MYC and glucocorticoid pathways.
AB  - Gene expression responses to glucocorticoid (GC) in the hours preceding onset of
      apoptosis were compared in three clones of human acute lymphoblastic leukemia CEM
      cells. Between 2 and 20h, all three clones showed increasing numbers of
      responding genes. Each clone had many unique responses, but the two responsive
      clones showed a group of responding genes in common, different from the resistant
      clone. MYC levels and the balance of activities between the three major groups of
      MAPKs are known important regulators of glucocorticoid-driven apoptosis in
      several lymphoid cell systems. Common to the two sensitive clones were changed
      transcript levels from genes that decrease amounts or activity of anti-apoptotic
      ERK/MAPK1 and JNK2/MAPK9, or of genes that increase activity of pro-apoptotic
      p38/MAPK14. Down-regulation of MYC and several MYC-regulated genes relevant to
      MAPKs also occurred in both sensitive clones. Transcriptomine comparisons
      revealed probable NOTCH-GC crosstalk in these cells.

PMID- 29596970
TI  - Cross-cultural adaptation of Roland-Morris Disability Questionnaire needs to
      assess the measurement properties: a systematic review.
AB  - OBJECTIVE: To assess the cross-cultural adaptations of the Roland-Morris
      Disability Questionnaire (RMDQ). STUDY DESIGN AND SETTING: English and Chinese
      databases were searched through December 2017. Cross-cultural adaptation and
      measurement properties were evaluated using the Guidelines for the Process of
      Cross-Cultural Adaptation of Self-Report Measures and the Quality Criteria for
      Psychometric Properties of Health Status Questionnaire. RESULTS: Among 34
      studies, there were 31 RMDQ adaptations for 26 different languages/cultures. In
      the cross-cultural adaptation process, few studies reported expert committees
      completely constituted (3/31), and only 10 studies completed the test of the
      prefinal version (10/31) due to insufficient sample sizes. As for the measurement
      properties, content validity (31/31) and construct validity (24/31) were assessed
      in most of the adaptations, whereas internal consistency (0/31), agreement
      (5/31), responsiveness (3/31), interpretability (6/31), and floor and ceiling
      effects (6/31) were not. CONCLUSION: The Hungarian and Moon's Korean adaptations
      were the highest quality translations. Where there were multiple adaptations for
      a language/culture, the Moon's Korean and Fan's simplified Chinese-Chinese
      Mainland adaptations are recommended over the other Korean or simplified Chinese
      Chinese Mainland adaptations. Further studies are required to fully assess the
      measurement properties of the Arabic-Moroccan, Arabic-Tunisian, German-Austrian,
      Greek, Gujarati, Kim's Korean, Persian-Iranian, Polish, He's simplified Chinese
      Chinese Mainland, Spanish, Spanish-Chilean, Thai, traditional Chinese-Taiwan, and
      Turkish adaptations of the RMDQ.

PMID- 29596971
TI  - Reply to: Letter to the Editor by M. Olsen, M. K. Sharp, and P. M. Bossuyt.

PMID- 29596972
TI  - A review of cluster randomized trials found statistical evidence of selection
      bias.
AB  - OBJECTIVES: To assess markers of selection bias risk in a sample of recently
      published cluster randomized controlled trials compared with individually
      randomized trials. STUDY DESIGN AND SETTING: We used OVID Medline and the online
      archives of the Journal of the American Medical Association to search for cluster
      randomized trials published between January 2015 and June 2017 from four high
      impact journals and compared them to a matched sample of individually randomized
      trials. RESULTS: We identified 23 cluster trials: 57% (n = 13) described a robust
      allocation method and 17% (n = 4) recruited all participants before
      randomization. Four (17%), eight (35%), and 11 (48%) were classified as at low,
      medium, and high bias risk, respectively. Meta-analysis showed significant age
      imbalance (-0.05, 95% CI = -0.057 to -0.043, I2 = 93.2%) in cluster trials, while
      the matched individually randomized trials showed no imbalance (0.005, 95% CI = 
      0.026 to 0.035, I2 = 0%). Cluster trials finding a statistically significant
      outcome in their primary measure showed a larger age imbalance (0.082, 95% CI = 
      0.091 to -0.073, I2 = 87%) than trials finding a nonstatistically significant
      outcome (0.022, 95% CI = 0.008 to 0.035, I2 = 83%). CONCLUSIONS: There is strong
      evidence in this sample of an effect of selection bias seen in an imbalance in
      baseline participant age, something not seen in a comparable sample of
      individually randomized trials.

PMID- 29596973
TI  - From the theoretical to the practical: how to evaluate the ethical and scientific
      justifications of randomized clinical trials.

PMID- 29596974
TI  - Pancratium triflorum Roxb. (Amaryllidaceae) and Molineria trichocarpa (Wight)
      N.P. Balakr (Hypoxidaceae): Cytotoxic and antioxidant activities.
AB  - The present investigation was carried out to evaluate the antioxidant and
      cytotoxic activities of Pancratium triflorum Roxb and Molineria trichocarpa were
      collected from South Vagaikulam, Tirunelveli district, Tamil Nadu, India. The
      antioxidant activities of P. triflorum extracts were as follows with the IC50
      values methanol (228.13 MUg/mL) > chloroform (311.33 MUg/mL) > acetone (398.08
      MUg/mL) > petroleum ether (410.16 MUg/mL). The antioxidant activities of P.
      triflorum and M. trichocarpa extracts were as follows with the IC50 values
      methanol (80.93 MUg/mL) > acetone (98.02 MUg/mL) > chloroform (186.84 MUg/mL) >
      petroleum ether (209.64 MUg/mL). Among the various extracts of P. triflorum,
      methanolic extracts showed the strongest phosphomolybdenum reduction (140.56 g
      AA/100 g). Among the tested extracts, acetone extracts of M. trichocarpa showed
      maximum inhibition with 71.36 +/- 5.86%. In P. triflorum, chloroform extracts
      showed maximum inhibition (69.51%). The petroleum ether extract of M. trichocarpa
      was found to be most effective at which 50% mortality (LC50) and 90% mortality
      (LC90) of brine shrimp nauplii were found to be 29.22 and 184.82 mg/mL. This
      study results revealed the antioxidant and cytotoxic properties of P. triflorum
      and M. trichocarpa. Further investigations are needed to isolate and validate the
      active principles of the extract responsible various pharmacological properties.

PMID- 29596975
TI  - Role of cytochrome P450 enzymes in fimasartan metabolism in vitro.
AB  - Fimasartan (FMS), an angiotensin II receptor antagonist, is metabolized to FMS S
      oxide, FMS N-glucuronide, oxidative desulfurized FMS (BR-A-557), and hydroxy-n
      butyl FMSs. The purpose of this study was to characterize enzymes involved in
      NADPH-dependent FMS metabolism using recombinant enzymes such as cytochrome P450
      (CYP) and flavin-containing monooxygenase (FMO), as well as selective chemical
      inhibitors. The results showed that CYP, but not FMO, plays a major role in FMS
      metabolism. CYP2C9, CYP3A4, and CYP3A5 were involved in the formation of FMS S
      oxide, which was further metabolized to BR-A-557 by CYP3A4/5. CYP2C9 played an
      exclusive role in n-butyl hydroxylation. The specificity constant (kcat/Km)
      values for S-oxidation by CYP2C9, CYP3A4, and CYP3A5 were 0.21, 0.34, and 0.19
      MUM-1?min-1, respectively. The kcat/Km values of hydroxylation at the 1-, 2-/3-,
      and 4-n-butyl group in CYP2C9 were 0.0076, 0.041, and 0.035 MUM-1?min-1,
      respectively. The kcat and Km values provide information for the prediction of
      FMS metabolism in vivo. In addition, simultaneous determination of the FMS
      metabolites may be used to evaluate CYP2C9 and CYP3A4/5 activity.

PMID- 29596976
TI  - NBD-BPEA regulates Zn2+- or Cu2+-induced Abeta40 aggregation and cytotoxicity.
AB  - Abnormal interaction of amyloid-beta peptide (Abeta) and metal ions is proved to
      be related to the etiology of Alzheimer's disease (AD). Using metal chelators to
      reverse metal-triggered Abeta aggregation has become one of the potential
      therapies for AD. In our work, the effect of metal chelator, NBD-BPEA, on Zn2+-
      or Cu2+-mediated Abeta40 aggregation and neurotoxicity has been systematically
      studied. NBD-BPEA exhibits the capability to inhibit the metal-mediated Abeta40
      aggregation and disassemble performed Abeta40 aggregates. It also prevents the
      formation of the beta-sheet structure and promotes the reversion of the beta
      sheet to the normal random coil conformation. Moreover, it can alleviate Zn2+- or
      Cu2+-Abeta40-induced neurotoxicity, suppress the intracellular ROS and protect
      against cell apoptosis. These preliminary findings indicate that NBD-BPEA has
      promising perspective of application in the treatment of AD, and therefore
      deserve further investigation as potential anti-AD agents.

PMID- 29596978
TI  - Fast and robust Block-Sparse Bayesian learning for EEG source imaging.
AB  - We propose a new Sparse Bayesian Learning (SBL) algorithm that can deliver fast,
      block-sparse, and robust solutions to the EEG source imaging (ESI) problem in the
      presence of noisy measurements. Current implementations of the SBL framework are
      computationally expensive and typically handle fluctuations in the measurement
      noise using different heuristics that are unsuitable for real-time imaging
      applications. We address these shortcomings by decoupling the estimation of the
      sensor noise covariance and the sparsity profile of the sources, thereby yielding
      an efficient two-stage algorithm. In the first stage, we optimize a simplified
      non-sparse generative model to get an estimate of the sensor noise covariance and
      a good initialization of the group-sparsity profile of the sources. Sources
      obtained at this stage are equivalent to those estimated with the popular inverse
      method LORETA. In the second stage, we apply a fast SBL algorithm with the noise
      covariance fixed to the value obtained in the first stage to efficiently shrink
      to zero groups of sources that are irrelevant for explaining the EEG
      measurements. In addition, we derive an initialization to the first stage of the
      algorithm that is optimal in the least squares sense, which prevents delays due
      to suboptimal initial conditions. We validate our method on both simulated and
      real EEG data. Simulations show that the method is robust to measurement noise
      and performs well in real-time, with faster performance than two state of the art
      SBL solvers. On real error-related negativity EEG data, we obtain source images
      in agreement with the experimental literature. The method shows promise for real
      time neuroimaging and brain-machine interface applications.

PMID- 29596977
TI  - Isoline use in crop composition studies with genetically modified crops under
      EFSA guidance - Short communication.
AB  - The European Food Safety Authority (EFSA) oversees the safety evaluation of
      genetically modified (GM) crops in the European Union. EFSA requires inclusion of
      commercial non-GM reference lines and a non-GM isoline in crop composition
      studies with GM crops. Reference lines are used to construct equivalence limits
      for each compositional analyte. Results for the GM line are compared with these
      equivalence limits to assess compositional equivalence between the GM crop and
      the non-GM crop. If compositional equivalence cannot be concluded from this
      comparison, then results for the non-GM isoline can be used to determine if this
      finding is likely the result of the background non-GM genetics of the GM crop. If
      this latter comparison is not sufficient to assess the compositional safety of
      the GM crop, then a biological-relevance assessment for the analytes in question
      can be completed taking into account the greater body of knowledge of composition
      for the crop and diets. Thus, the isoline is a useful comparator but not required
      to assess the compositional safety of the GM crop, and therefore, unavoidable
      genotype differences between the isoline and GM line should not be grounds for
      rejection of compositional studies where the biological relevance of potential
      non-equivalence is addressed.

PMID- 29596979
TI  - Hemispheric asymmetry and homotopy of resting state functional connectivity
      correlate with visuospatial abilities in school-age children.
AB  - Hemispheric specialization of cognitive functions is a developmental process that
      shapes the brain from the gestational stage to adulthood. Functional connectivity
      of the resting brain has been largely used to infer the hemispheric organization
      of the spontaneous brain activity. In particular, two main properties have been
      largely explored throughout development: hemispheric asymmetry of functional
      connectivity and homotopic functional connectivity. However, their relation with
      specific cognitive processes typically associated with hemispheric
      specialization, such as visuospatial abilities, remains largely unexplored. Such
      relationships could be particularly relevant for the quest of developmental
      cognitive biomarkers in childhood, a significant maturation period of
      visuospatial abilities. Moreover, the relation between asymmetry and homotopy of
      brain functional connectivity is not well understood. We have examined these two
      properties in a sample of 60 typically developing children between 6 and 10 years
      of age, and explored their relation with visuospatial abilities. First, we
      identified a strong negative relation between homotopy and asymmetry across the
      brain. In addition, these properties showed areas in the posterior portion of the
      brain, with significant correlation with performance in visual memory and visual
      attention tasks. These results highlight the relevance of the hemispheric
      organization of spontaneous brain activity for developmental cognition,
      particularly for visuospatial abilities.

PMID- 29596980
TI  - SMAC: Spatial multi-category angle-based classifier for high-dimensional
      neuroimaging data.
AB  - With the development of advanced imaging techniques, scientists are interested in
      identifying imaging biomarkers that are related to different subtypes or
      transitional stages of various cancers, neuropsychiatric diseases, and
      neurodegenerative diseases, among many others. In this paper, we propose a novel
      spatial multi-category angle-based classifier (SMAC) for the efficient
      identification of such imaging biomarkers. The proposed SMAC not only utilizes
      the spatial structure of high-dimensional imaging data but also handles both
      binary and multi-category classification problems. We introduce an efficient
      algorithm based on an alternative direction method of multipliers to solve the
      large-scale optimization problem for SMAC. Both our simulation and real data
      experiments demonstrate the usefulness of SMAC.

PMID- 29596981
TI  - The vestibulomyogenic balance response is elevated following high-intensity
      lengthening contractions of the lower limb.
AB  - The purpose was to investigate whether exercise-induced muscle weakness of the
      plantar and dorsiflexors through high-intensity lengthening contractions
      increases the vestibulomyogenic balance response. Nine males (~25 years)
      participated in three experimental testing days to evaluate the vestibular
      control of standing balance and neuromuscular function of the plantar and
      dorsiflexors pre- and post (30 min, and 1 and 7 days) high-intensity lengthening
      plantar and dorsiflexions. To evaluate the vestibular-evoked balance response,
      participants stood quietly on a force plate while exposed to continuous, random
      electrical vestibular stimulation (EVS) for two 90-s trials. Relationships
      between EVS-antero-posterior (AP) forces and EVS-medial gastrocnemius
      electromyography (EMG) were estimated in the frequency domain (i.e., coherence).
      Weakness of the right plantar and dorsiflexors were assessed using maximal
      voluntary contraction (MVC) torque. The lengthening contractions induced a 13 and
      24% reduction in plantar and dorsiflexor MVC torque, respectively (p < 0.05) of
      the exercised leg, which did not recover by 1 day post. The EVS-EMG coherence
      increased over a range of frequencies up to 7 days post compared to pre
      lengthening contractions. Conversely, EVS-AP forces coherence exhibited limited
      changes. The greater EVS-EMG coherence post exercise-induced muscle weakness may
      be a compensatory mechanism to maintain the whole-body vestibular-evoked balance
      response when muscle strength is reduced.

PMID- 29596982
TI  - Vedolizumab Treatment May Reduce Steroid Burden and Improve Histology in Patients
      With Eosinophilic Gastroenteritis.

PMID- 29596983
TI  - Dyspepsia.

PMID- 29596985
TI  - NEWSworthy but Not Ready for Prime Time.

PMID- 29596984
TI  - Cost Effectiveness of Biomarker Tests for Irritable Bowel Syndrome With Diarrhea:
      A Framework for Payers.
AB  - BACKGROUND & AIMS: Diagnosis of diarrhea-predominant irritable bowel syndrome
      (IBS-D) relies on the Rome IV symptom-based criteria, which are imperfect for
      separating functional vs organic disease. Biomarker tests for IBS-D might be
      added to symptom data to allow clinicians to make more accurate and precise
      diagnoses in a cost-effective manner. We tested the economic consequences of
      using a range of hypothetical IBS-D biomarkers, and explored at what cost and
      level of accuracy a biomarker becomes cost effective. We produced a framework for
      payers to evaluate the return on an investment of implementing IBS-D biomarkers
      of varying accuracy and cost. METHODS: We used decision analysis software to
      evaluate a hypothetical cohort of patients who met Rome IV criteria for IBS-D. We
      conducted cost-utility and budget impact analyses of 2 competing approaches:
      usual care or an IBS biomarker-based diagnostic approach. Patients in the usual
      care group received empiric IBS treatment; non-responders received additional
      diagnostic tests for organic disease. In the group evaluated with a biomarker
      test, those with a positive result received IBS treatment before additional
      diagnostic analyses, whereas patients with a negative result underwent upfront
      diagnostic testing. Outcomes were incremental cost per quality-adjusted life year
      gained (third-party payer perspective) and incremental per-member per-month cost.
      RESULTS: In the base-case analysis, using a willingness-to-pay threshold of
      $100,000/quality-adjusted life year, we found that biomarkers are not cost
      effective when the biomarker test costs more than $846, even if the test is 100%
      accurate in detecting IBS-D. In probabilistic analysis using 1,000 simulations,
      most trials (75% or more) show that the biomarker-based diagnostic approach is
      cost effective above the following accuracy thresholds: a $100 biomarker test
      with 51% accuracy, a $200 test with 57% accuracy, a $300 test with 63% accuracy,
      a $400 test with 69% accuracy, a $500 test with 76% accuracy, a $600 test with
      82% accuracy, a $700 test with 89% accuracy, and a $800 test with 94% accuracy.
      CONCLUSIONS: In decision analysis of a hypothetical cohort of patients who met
      Rome IV criteria for IBS-D, we identified cost and accuracy thresholds that can
      guide investigators and payers as they develop, validate, price, and/or reimburse
      IBS-D biomarker tests for use in everyday clinical practice.

PMID- 29596986
TI  - Is Modest Drinking Good for the Liver?

PMID- 29596988
TI  - The detection and prevalence of leukotoxin gene variant strains of Fusobacterium
      necrophorum in footrot lesions of sheep in Kashmir, India.
AB  - The objective of this study was to determine the prevalence and identification of
      leukotoxin gene, lktA, variant strains of Fusobacterium necrophorum in the
      footrot lesions of sheep. The detection of F. necrophorum was carried out by PCR
      targeting the lktA gene fragment and identification of lktA variant strains was
      done by PCR-single stranded conformational polymorphism (PCR-SSCP) and gene
      sequencing. Of the 450 swabs collected from footrot lesions of sheep, 117 were
      lktA-positive for F. necrophorum. Of the 50 swabs collected from apparently
      asymptomatic sheep, only one was lktA-positive for F. necrophorum. The overall
      prevalence of F. necrophorum in footrot affected sheep in Kashmir valley was 26%,
      and ranged from 20 to 34.8%, respectively. PCR-SSCP of lktA gene fragment
      analysis revealed three lktA variants, designated as JKS-F1/F2/F3, while two
      samples (1.7%) showed multiple lktA variant strains of F. necrophorum in a single
      footrot-affected sheep hoof. This appears to be the first report on the presence
      of more than one lktA variant of F. necrophorum in a footrot lesion of sheep. The
      JKS-F3 lktA variant was the most frequent (75.4%), followed by JKS-F2 (14.4%) and
      JKS-F1 (8.4%), respectively. Among the three lktA variants identified, JKS-F3 was
      detected in 74 (86.0%) samples from severe footrot affected sheep with a lesion
      score of 4. The data suggest that JKS-F3 is the predominant lktA variant of F.
      necrophorum and is associated with severe footrot in sheep. Hence, JKS-F3 may be
      a significant variant contributing to the severity and duration of the disease in
      sheep.

PMID- 29596987
TI  - Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials
      of Crohn's Disease: A Systematic Review.
AB  - BACKGROUND & AIMS: Endpoints in randomized controlled trials (RCTs) of Crohn's
      disease (CD) are changing. We performed a systematic review of efficacy and
      safety outcomes reported in placebo-controlled RCTs of patients with CD. METHODS:
      We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017
      for placebo-controlled RCTs of adult patients with CD treated with
      aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small
      molecules. Efficacy and safety outcomes, definitions, and measurement tools were
      collected and stratified by decade of publication. RESULTS: Our final analysis
      included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention
      trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in
      all trials; the most common endpoint was CD activity index score. We identified
      38 unique definitions of clinical response or remission and 32 definitions of
      loss of response. Definitions of endoscopic response, remission, and endoscopic
      healing were also heterogeneous, evaluated using the CD endoscopic index of
      severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts'
      Score for postoperative endoscopic appearance. Histologic outcomes were reported
      in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of
      postoperative prevention trials. Biomarker outcomes were reported in 81.5%
      induction trials, 68.2% of maintenance trials, and 42.9% of postoperative
      prevention trials. Safety outcomes were reported in 93.8% of induction trials,
      97.7% of maintenance trials, and 85.7% of postoperative prevention trials.
      CONCLUSIONS: In this systematic review, we demonstrate heterogeneity in
      definitions of response and remission, and changes in outcomes reported in RCTs
      of CD. It is a priority to select a core set of outcomes to standardize efficacy
      and safety evaluation in trials of patients with CD.

PMID- 29596989
TI  - High-level expression, purification, and enzymatic characterization of a
      recombinant Aspergillus sojae alkaline protease in Pichia pastoris.
AB  - An alkaline protease (Ap) was cloned from Aspergillus sojae GIM3.33 via RT-PCR
      technique. A truncated Ap without the signal peptide was successfully expressed
      in the Pichia pastoris KM71 strain. The following describes the optimal process
      conditions for the recombinant engineering of a strain expressing a recombinant
      Ap (rAp) in a triangular flask: inoculum concentration OD600 value 20.0 in 40 mL
      working volume (in 500 mL flasks), methanol addition (1.0%; volume ratio), 0.02%
      biotin solution (60 MUL), and YNB primary concentration (13.0 g/L). Under these
      conditions, the protease activity of rAp in the fermentation broth reached 400.4
      +/- 40.5 U/mL after induction for three days. The rAp was isolated and purified,
      and its enzymatic characteristics were tested. Its optimal pH was 10.0, and it
      remained stable in a pH range of 7.0-10.0. Its optimal temperature was 45 
      degrees C and it retained >50% activity at 40  degrees C for 60 min. The rAp
      activity was significantly inhibited by PMSF, Zn2+ and Fe2+ and the rAp had a
      broad substrate specificity for natural proteins and synthetic peptide
      substrates, and preferred substrates at P1 position with large hydrophobic side
      chain groups. Compared to Papain (8.7%) and Alcalase (12.2%), the degree of
      hydrolysis of rAp to soy protein isolate was 16.5%; therefore, rAp was a good
      candidate for the processing of food industry byproducts.

PMID- 29596990
TI  - Improved inducible expression of Bacillus naganoensis pullulanase from
      recombinant Bacillus subtilis by enhancer regulation.
AB  - Pullulanase is crucial to the specific hydrolysis of branch points in amylopectin
      and is generally employed as an important enzyme in the starch-processing
      industry. Recombinant Bacillus subtilis that employs an inducible promoter would
      be a suitable candidate for pullulanase expression because of its safety and
      controllable production, but its level of pullulanase activity is relatively low.
      In this study, we investigated the effect of the enhancers DegQ, DegU, and DegS
      on pullulanase expression in a recombinant B. subtilis inducible system. The
      genes degQ, degU, and degS were introduced to the recombinant plasmid pMA0911
      PsacB-pul harboring the promoter PsacB, signal peptide LipA, and gene encoding
      pullulanase. The regulatory effects of the enhancers involved in recombinant
      plasmids on pullulanase expression level were evaluated in B. subtilis WB600 and
      WB800, respectively. The positive regulation of DegQ toward pullulanase
      expression was detected from B. subtilis WB800, leading to a 60% increase in
      enzyme activity. In addition, enzyme activity was further enhanced by inserting
      the degQ gene to the position closer to the promoter PsacB. Consequently,
      pullulanase activity reached 26.5 U ml-1 from the B. subtilis WB800/pMA0911-PsacB
      pul-degQ(N) after expression optimization, which was a 5.9-fold increase
      compared to that of the original strain B. subtilis WB800/pMA0911-PsacB-pul.
      Hence, the inducible expression of the enzyme was efficiently enhanced by
      regulating the enhancer DegQ from recombinant B. subtilis WB800.

PMID- 29596991
TI  - A novel strategy to produce high level and high purity of bioactive IL15 fusion
      proteins from mammalian cells.
AB  - IL15, a member of the common gamma chain receptor (gammac) cytokine family, is
      gaining attention in recent years as one of the most promising anti-tumor agents.
      IL15 regulates T cell activation and proliferation, promotes the survival of CD8+
      CD44hi memory T cells and is also essential for NK cell expansion and
      development. Despite the attraction of developing IL15 as an anti-cancer agent,
      production of recombinant IL15 has proven to be difficult due to the stringent
      control of IL15 expression at the transcriptional, translational and the post
      translational levels. Furthermore, the bioactivity of IL15 fused to an extra
      functional domain that is isolated from mammalian cells is generally inferior to
      recombinant IL15 produced by E. coli. In this study, we report that Lysine 86 in
      IL15 is responsible for the instability in mammalian cells when its C-terminus is
      fused to the albumin binding scFv (IL15-A10m3). We demonstrate that K86A or K86R
      mutants increased the expression of the fusion protein from HEK293 cells. When
      the wild type IL15 is used for the fusion, no recombinant IL15 fusion was
      detected in the culture media. Additionally, we determined that the residue 112
      in IL15 is critical for the bioactivity of IL15-A10m3. Examination of single and
      double mutants provides a better understanding of how IL15 engages with its
      receptor complex to achieve full signaling capacity. The results of our
      experiments were successfully applied to scale up production to levels up to 50
      mg/L and >10 mg/L of >95% pure monomeric recombinant fusion proteins after a 2
      step purification from culture media. More importantly, the recombinant fusion
      protein produced is fully active in stimulating T cell proliferation, when
      compared to the recombinant wild type IL15.

PMID- 29596992
TI  - Complement-fixing donor-specific anti-HLA antibodies and kidney allograft
      failure.
AB  - Detection of donor-specific antibodies (DSA) has improved the risk classification
      and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA
      C1q-binding ability has been shown to improve the individual risk classification
      of transplant patients for allograft loss, especially when detected after
      transplantation. The aim of this study was to evaluate the additional clinical
      impact of C1q-binding DSA detection in a population that was extensively
      monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were
      followed-up at multiple time points for up to 5 years after transplantation for
      the presence of anti-HLA DSA-IgG total. The samples that were positive for these
      antibodies were retrospectively tested for the presence of complement-binding
      antibodies. Overall, 24 patients presented DSA, 29% (7) of which also produced
      complement-binding DSA. Compared to patients with non-C1q-binding DSA and non
      sensitized patients, patients with C1q-binding DSA after transplantation had the
      lowest allograft survival rate at 5 years (p = 0.042) and showed a lower
      estimated glomerular filtration rate (based on the Modification of Diet in Renal
      Disease formula) during the post-transplant follow-up period (p = 0.01). Thus,
      post-transplant monitoring for complement-binding DSA is a useful tool for
      predicting individuals most at risk for allograft failure, and might also be
      beneficial for evaluation of immunosuppression regimens.

PMID- 29596993
TI  - Immune modulation by silencing CD80 and CD86 production in dendritic cells using
      small hairpin RNA to reduce heart transplant rejection.
AB  - RNA interference (RNAi) plays a potential role in organ transplantation. Small
      hairpin RNA (shRNA) is an artificial RNA molecule with a tight hairpin turn that
      can be used to silence the expression of a target gene. We constructed shRNA
      targeting on the cluster of differentiation 80 (CD80, B7-1) and the cluster of
      differentiation 86 (CD86, B7-2) and transfected it into dendritic cells (DCs).
      Fluorescence real-time PCR and flow cytometry confirmed the gene-silencing
      effect. Interleukin-2 (IL-2) mRNA expression level decreased in T cells that were
      cocultured with pB7-shRNA-transfected DCs. For in-vivo experiment, we built mice
      models of abdominal heterotopic heart transplantation and transfused the models
      with pB7-shRNA-transfected donor-derived DCs. The survival time of the
      transplanted heart increased; the grade of organ rejection decreased. IL-2 mRNA
      expression level decreased and it was positively correlated with the grade of
      organ rejection.

PMID- 29596994
TI  - Convergent engineering of syntrophic Escherichia coli coculture for efficient
      production of glycosides.
AB  - Synthetic microbial coculture to express heterologous biosynthetic pathway for de
      novo production of medicinal ingredients is an emerging strategy for metabolic
      engineering and synthetic biology. Here, taking efficient production of
      salidroside as an example of glycosides, we design and construct a syntrophic
      Escherichia coli-E. coli coculture composed of the aglycone (AG) strain and the
      glycoside (GD) strain, which convergently accommodate biosynthetic pathways of
      tyrosol and salidroside, respectively. To accomplish this the phenylalanine
      deficient AG strain was engineered to utilize xylose preferentially and to
      overproduce precursor tyrosol, while the tyrosine-deficient GD strain was
      constructed to consume glucose exclusively and to enhance another precursor UDP
      glucose availability for synthesis of salidroside. The AG and GD strains in the
      synthetic consortium are obligatory cooperators through crossfeeding of tyrosine
      and phenylalanine and compatible in glucose and xylose mixture. Through balancing
      the metabolic pathway strength, we show that the syntrophic coculture was robust
      and stable, and produced 6.03 g/L of salidroside. It was the de novo production
      of salidroside for the first time in E. coli coculture system, which would be
      applicable for production of other important glycosides and natural products.

PMID- 29596995
TI  - Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1
      related BDNF.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with
      concurrent anxiety and depression symptoms, and reduce the expression of the
      Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and
      survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated
      channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate
      depression and anxiety, and regulated the BDNF expression, however, the effects
      of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have
      been poorly perceived. METHODS: In the present study, the effects of ketamine
      were examined on the PTSD-like effects in a rat model of PTSD induced by SPS&S
      procedure. After the SPS&S procedure and model testing, PTSD rats were subjected
      to behavioral testing and biochemical assessments, followed by single treatment
      with certain doses of ketamine (5, 10, 15 and 20 mg/kg IP). RESULTS: The results
      showed that the SPS&S procedure induced severe PTSD-like behaviors, with lower
      levels of BDNF protein levels and higher level of the HCN1 protein in the
      prefrontal cortex (PFC). These were reversed by a single administration of
      ketamine. The ketamine with dose of 15 mg/kg significantly increased locomotor
      behavior in the open field test, aggrandized exploratory behavior in the elevated
      plus maze test, and decreased immobility time spent in the forced swim test.
      Meanwhile, ketamine with dose of 15 mg/kg could increase the BDNF protein level,
      while down-regulate the expression of the HCN1. Eventually, there was a negative
      correlation between the level of BDNF and HCN1 in the PFC. CONCLUSION: Ketamine
      affects the HCN1-related BDNF signaling pathways to alleviate PTSD-like effects
      in rat.

PMID- 29596996
TI  - Unpredictable chronic prenatal stress and manifestation of generalized anxiety
      and panic in rat's offspring.
AB  - Often the manifestation of anxiety cannot be explained by known environmental or
      hereditary factors. With this perspective, it has been reported that prenatal
      stress may lead to emotional disturbances in the offspring. However, studies
      relating prenatal stress to anxiety are controversial and generally the stressors
      used do not mimicks the reality experienced by mothers. Thus, this investigation
      evaluated the effects of an unpredictable chronic stress scheme applied in one of
      the three gestational weeks of rats on the manifestation of generalized anxiety
      and panic disorder in the progeny (males), analyzing, respectively, the
      avoidances and escapes in the elevated T-maze, at the 1st, 3rd or 6th month of
      progeny life. Control offspring showed increased generalized anxiety disorder and
      reduced panic at 6 months. The effects of prenatal stress depended on the
      gestational week where it occurred and on the progeny age: during the 1st
      gestational week the generalized anxiety decreased in 6 month old rats. Animals
      in the 3rd month, prenatally stressed during the last gestational week, showed
      anxiogenesis and panicogenesis, but effects reverted at the 6th month, when they
      presented anxiolysis and no changes related to panic. Together the results show
      that not only the gestational period in which the aversive experience occurred
      was important, but the age of the evaluated progeny, since the type and the
      intensity of behaviors related to anxiety may vary with the developmental stage.
      For the model of stress used in the present study, the effects of prenatal stress
      were more prominent when the exposure occurred during the 3rd gestational week in
      rats.

PMID- 29596997
TI  - Regarding "A Polypectomy Nearly Becoming a Tragedy: A Case of Multiorgan
      Perforation".

PMID- 29596998
TI  - Regarding "Reproductive Outcomes of Segmented In Vitro Fertilization in Patients
      Diagnosed with Endometriomas".

PMID- 29597000
TI  - Cough reflex sensitivity does not correlate with the esophageal sensitivity to
      acid in patients with gastroesophageal reflux disease.
AB  - The sensitization of cough reflex observed in patients with gastroesophageal
      reflux disease (GERD) is attributed to activation of vagal C-fibers innervating
      the esophagus by acid, while the heartburn in GERD is mediated by esophageal acid
      sensitive C-fibers derived from (dorsal root ganglia) DRG. Here we explored the
      relationship between cough reflex sensitivity (CRS) and esophageal sensitivity to
      acid. We evaluated CRS to capsaicin inhalation and esophageal sensitivity to acid
      (intensity of heartburn evoked by esophageal infusions of acid pH = 3, 2 and 1)
      in patients with GERD and chronic heartburn before and 3 months after proton pump
      inhibitor (PPI) treatment. There was no correlation between CRS and esophageal
      sensitivity to acid at any pH tested. PPI treatment substantially reduced
      esophageal sensitivity to acid but did not affect CRS. We conclude that a simple
      direct relationship between CRS and esophageal sensitivity to acid is unlikely.
      The results indicate that spinal and vagal afferent pathways from the esophagus
      are probably influenced separately in subjects with GERD.

PMID- 29596999
TI  - Tithonia diversifolia (Hemsl.) A. Gray as a medicinal plant: A comprehensive
      review of its ethnopharmacology, phytochemistry, pharmacotoxicology and clinical
      relevance.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tithonia diversifolia (TD) is widely valued in
      several cultures for its medicinal properties. A comprehensive review of the
      current understanding of this plant species is required due to emerging concerns
      over its efficacy, toxicity and allergenic potential. AIM OF THE REVIEW: We
      critically summarized the current evidence on the botany, traditional use,
      phytochemistry, pharmacology and safety of TD, with the view to provide
      perspectives for developing more attractive pharmaceuticals of plant origin, but
      also to lay a new foundation for further investigations on this plant. MATERIALS
      AND METHODS: A preliminary consultation of search engines such as Web of Science,
      PubMed, ScienceDirect and other published/unpublished resources provided an
      overview of extant literature on TD. Then, we meticulously screened all titles,
      abstracts and full-texts to establish consistency in the application of inclusion
      criteria. Studies were considered for inclusion if they dealt with taxonomy,
      global distribution, local and traditional knowledge, phytochemistry, toxicity
      and biological effects. RESULTS: 1856 articles were retrieved among which 168
      were revised and included. Several studies conducted on cell lines and animals
      provided supporting evidence for some ethnomedicinal claims of extracts from TD.
      Short-term use of Tithonia extracts were effective and well-tolerated in animals
      when taken at lower doses. Both the toxic and therapeutic effects were attributed
      to bioactive principles naturally occurring in this species including
      sesquiterpene lactones, chlorogenic acid and flavonoids. CONCLUSIONS: T.
      diversifolia is a valuable source of bioactive compounds with significant
      therapeutic implications and favourable safety index. However, more rigorously
      designed investigations are needed to recommend the whole plant or its active
      ingredients as a medication, and should focus on understanding the multi-target
      network pharmacology of the plant, clarifying the effective doses as well as
      identifying the potential interactions with prescribed drugs or other chemicals.

PMID- 29597001
TI  - Novel computer algorithm for cough monitoring based on octonions.
AB  - The objective assessment of cough frequency is essential for evaluation of cough
      and antitussive therapies. Nonetheless, available algorithms for automatic
      detection of cough sound have limited sensitivity and the analysis of cough sound
      often requires input from human observers. Therefore, an algorithm for the cough
      sound detection with high sensitivity would be very useful for development of
      automatic cough monitors. Here we present a novel algorithm for cough sounds
      classification based on 8-dimensional numbers octonions and compare it with the
      algorithm based on standard neural network. The performance was evaluated on a
      dataset of 5200 cough sounds and 90000 of non-cough sounds generated from the
      sound recordings in 18 patients with frequent cough caused by various respiratory
      diseases. Standard classification algorithm had sensitivity 82.2% and specificity
      96.4%. In contrast, octonionic classification algorithm had significantly higher
      sensitivity 96.8% and specificity 98.4%. The use of octonions for classification
      of cough sounds improved sensitivity and specificity of cough sound detection.

PMID- 29597002
TI  - A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High
      Risk Acute Myeloid Leukemia.
AB  - Natural killer (NK) cells are an emerging immunotherapy approach to acute myeloid
      leukemia (AML); however, the optimal approach to activate NK cells before
      adoptive transfer remains unclear. Human NK cells that are primed with the CTV-1
      leukemia cell line lysate CNDO-109 exhibit enhanced cytotoxicity against NK cell
      resistant cell lines. To translate this finding to the clinic, CNDO-109-activated
      NK cells (CNDO-109-NK cells) isolated from related HLA-haploidentical donors were
      evaluated in a phase 1 dose-escalation trial at doses of 3 * 105 (n = 3), 1 * 106
      (n = 3), and 3 * 106 (n = 6) cells/kg in patients with AML in first complete
      remission (CR1) at high risk for recurrence. Before CNDO-109-NK cell
      administration, patients were treated with lymphodepleting
      fludarabine/cyclophosphamide. CNDO-109-NK cells were well tolerated, and no dose
      limiting toxicities were observed at the highest tested dose. The median relapse
      free survival (RFS) by dose level was 105 (3 * 105), 156 (1 * 106), and 337 (3 *
      106) days. Two patients remained relapse-free in post-trial follow-up, with RFS
      durations exceeding 42.5 months. Donor NK cell microchimerism was detected on day
      7 in 10 of 12 patients, with 3 patients having evidence of donor cells on day 14
      or later. This trial establishes that CNDO-109-NK cells generated from related
      HLA haploidentical donors, cryopreserved, and then safely administered to AML
      patients with transient persistence without exogenous cytokine support. Three
      durable complete remissions of 32.6 to 47.6+ months were observed, suggesting
      additional clinical investigation of CNDO-109-NK cells for patients with myeloid
      malignancies, alone or in combination with additional immunotherapy strategies,
      is warranted.

PMID- 29597003
TI  - Prenatal and postnatal cigarette and cannabis exposure: Effects on Secretory
      Immunoglobulin A in early childhood.
AB  - AIMS: Secretory Immunoglobulin A (SIgA) plays a critical role in immune
      functioning by preventing pathogens from adhering to epithelial mucosa. Most
      infectious agents enter the body via mucosal surfaces, thus SIgA serves in the
      defense against respiratory, intestinal, and urinogenitary infections, as well as
      periodontal disease and caries. This study examined the possibility that pre- and
      postnatal exposure to cigarette and cannabis is associated with individual
      differences in Secretory Immunoglobulin A (SIgA) levels in early childhood.
      METHODS: Participants were 50 mother/infant (29 boys; 35% Caucasian) dyads
      recruited at their first prenatal appointment in a large northeastern community
      hospital in the United States. Repeated assessments of pre- and postnatal
      cigarette and cannabis were conducted beginning in the first trimester of
      pregnancy, using multiple methods (i.e., saliva, meconium, self-report). Infants
      were grouped into those prenatally exposed to either cigarette only (n = 19),
      cigarette and cannabis (n = 19), or with no prenatal substance exposure (n = 12).
      At age 5 years, the children's saliva was collected and assayed for SIgA.
      RESULTS: There were group differences in SIgA levels as a function of prenatal
      exposure to cigarette and cannabis - children in the cigarette only and the
      cigarette and cannabis groups had higher SIgA levels compared to the non-exposed
      children. Children who experienced the combination of postnatal exposure to
      cigarette and cannabis had higher levels of SIgA, even after accounting for
      prenatal exposures and other covariates relevant to immune system functioning.
      CONCLUSIONS: Prenatal and postnatal exposure to cigarette and cannabis may be
      associated with hyperactivity of mucosal immunity in early childhood. Links
      between cigarette and cannabis exposure and health problems in early childhood
      may be partially explained by prenatal and postnatal exposure-related changes in
      mucosal immunity.

PMID- 29597004
TI  - Neuroprotective effect of docosahexaenoic acid in rat traumatic brain injury
      model via regulation of TLR4/NF-Kappa B signaling pathway.
AB  - OBJECTIVE: The experiments were conducted to prove that docosahexaenoic acid
      (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B
      signaling pathway. METHODS: Bioinformatic analysis was performed using published
      data from Gene Expression Omnibus (GEO) database to investigate differentially
      expressed genes and signaling pathways. Controlled cortical impact (CCI) injury
      rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat
      TBI rats. Neurological severity score (NSS) and beam walking test and rotarod
      test were used to confirm whether DHA is neuron-protective against TBI. The
      expression of TLR4, NF-Kappa B p65, (TNF)-alpha and IL-1beta were examined by qRT
      PCR and western blot. The impact of DHA on neurocyte apoptosis was validated by
      TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The influence of DHA on
      CD11b and GFAP expression in the hippocampus was determined through
      immunohistochemical analysis. RESULTS: TLR4/NF Kappa B pathway was suggested to
      be closely correlated with TBI by bioinformatic analysis. DHA could improve the
      neurological function and learning and memory ability of rats after TBI as well
      as promote neurocytes from apoptosis. TLR4 expression and the expression of
      inflammatory mediator NF-Kappa B were also repressed by DHA treatment.
      CONCLUSIONS: DHA exerted a neuron-protective influence in a rat model of TBI via
      repressing TLR4/NF-Kappa B pathway.

PMID- 29597005
TI  - Non-syndromic retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies
      characterized by the primary degeneration of rod and cone photoreceptors. RP is a
      leading cause of visual disability, with a worldwide prevalence of 1:4000.
      Although the majority of RP cases are non-syndromic, 20-30% of patients with RP
      also have an associated non-ocular condition. RP typically manifests with night
      blindness in adolescence, followed by concentric visual field loss, reflecting
      the principal dysfunction of rod photoreceptors; central vision loss occurs later
      in life due to cone dysfunction. Photoreceptor function measured with an
      electroretinogram is markedly reduced or even absent. Optical coherence
      tomography (OCT) and fundus autofluorescence (FAF) imaging show a progressive
      loss of outer retinal layers and altered lipofuscin distribution in a
      characteristic pattern. Over the past three decades, a vast number of disease
      causing variants in more than 80 genes have been associated with non-syndromic
      RP. The wide heterogeneity of RP makes it challenging to describe the clinical
      findings and pathogenesis. In this review, we provide a comprehensive overview of
      the clinical characteristics of RP specific to genetically defined patient
      subsets. We supply a unique atlas with color fundus photographs of most RP
      subtypes, and we discuss the relevant considerations with respect to differential
      diagnoses. In addition, we discuss the genes involved in the pathogenesis of RP,
      as well as the retinal processes that are affected by pathogenic mutations in
      these genes. Finally, we review management strategies for patients with RP,
      including counseling, visual rehabilitation, and current and emerging therapeutic
      options.

PMID- 29597007
TI  - Design and Rationale for the Veterans Affairs "Cooperative Study Program 594
      Comparative Effectiveness in Gout: Allopurinol vs. Febuxostat" Trial.
AB  - BACKGROUND: Gout patients do not routinely achieve optimal outcomes related in
      part to suboptimal administration of urate lowering therapy (ULT) including first
      line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to
      the approval of febuxostat compared this agent to allopurinol in inappropriately
      low, fixed doses. We will compare allopurinol with febuxostat in gout using
      appropriately titrated doses of both agents and a "treat-to-target" strategy
      congruent with specialty guidelines. METHODS: We have planned and initiated the
      Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative
      Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind,
      non-inferiority trial will enroll 950 gout patients randomized to receive
      allopurinol or febuxostat. Patients will be followed for a total of 72 weeks
      encompassing 3 distinct 24-week study phases. During Phase I (0-24 weeks),
      participants will undergo gradual dose titration of ULT until achievement of
      serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose
      escalation will not be allowed during final three study visits of Phase 2 (24-48
      weeks) and during Phase 3 (48-72 weeks). The primary study outcome is the
      proportion of participants experiencing at least one gout flare during Phase 3.
      Subsequent to the 72-week study, participants will be followed passively for up
      to 10 years after the study to assess long-term health outcomes. CONCLUSION: With
      its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs
      Febuxostat study will demonstrate the central role of gradual ULT dose escalation
      and a treat-to-target strategy in gout management.

PMID- 29597006
TI  - Rationale and study protocol for Unidas por la Vida (United for Life): A dyadic
      weight-loss intervention for high-risk Latina mothers and their adult daughters.
AB  - BACKGROUND: Half of Mexican-American women are under-active and nearly 78% are
      overweight/obese. The high lifetime risk of developing type 2 diabetes
      necessitates a culturally appropriate lifestyle intervention. PURPOSE: Unidas por
      la Vida is a novel dyadic intervention that capitalizes on the centrality of
      family in Latino culture to mobilize an existing family dyad as a resource for
      health behavior change. The intervention aims to improve health behaviors and
      promote weight loss in two at-risk members of the same family: mothers with type
      2 diabetes and their overweight/obese adult daughters who are at risk for
      developing diabetes. METHODS: Participants (N = 460 mother-adult daughter dyads)
      will be randomized into one of three conditions: 1) dyadic participation (mothers
      daughters) in a lifestyle intervention; 2) individual participation (mothers
      alone; unrelated daughters alone) in a lifestyle intervention; and 3) mother
      daughter dyads in a minimal intervention control group. RESULTS: The primary
      outcome is weight loss. Secondary outcomes include physical activity, dietary
      intake, physiological measures (e.g. HbA1c), and body composition. Both the
      dyadic and individual interventions are expected to produce greater weight loss
      at 6, 12, and 18 months than those in minimal intervention control group, with
      women assigned to the dyadic intervention expected to lose more weight and to
      maintain the weight loss longer than women assigned to the individual
      intervention. CONCLUSION: Because health risks are often shared by multiple
      members of at-risk families, culturally appropriate, dyadic interventions have
      the potential to increase the success of behavior change efforts and to extend
      their reach to multiple family members. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier NCT02741037.

PMID- 29597008
TI  - Buccal venom gland associates with increased of diversification rate in the fang
      blenny fish Meiacanthus (Blenniidae; Teleostei).
AB  - At the macroevolutionary level, many mechanisms have been proposed to explain
      explosive species diversification. Among them morphological and/or physiological
      novelty is considered to have a great impact on the tempo and the mode of
      diversification. Meiacanthus is a genus of Blenniidae possessing a unique buccal
      venom gland at the base of an elongated canine tooth. This unusual trait has been
      hypothesized to aid escape from predation and thus potentially play an important
      role in their pattern of diversification. Here, we produce the first time
      calibrated phylogeny of Blenniidae and we test the impact of two morphological
      novelties on their diversification, i.e. the presence of swim bladder and buccal
      venom gland, using various comparative methods. We found an increase in the tempo
      of lineage diversification at the root of the Meiacanthus clade, associated with
      the evolution of the buccal venom gland, but not the swim bladder. Neither
      morphological novelty was associated with the pattern of size disparification in
      blennies. Our results support the hypothesis that the buccal venom gland has
      contributed to the explosive diversification of Meiacanthus, but further analyses
      are needed to fully understand the factors sustaining this burst of speciation.

PMID- 29597009
TI  - MicroRNA528 Affects Lodging Resistance of Maize by Regulating Lignin Biosynthesis
      under Nitrogen-Luxury Conditions.
AB  - Lodging under nitrogen (N)-luxury conditions substantially reduces crop yield and
      seed quality. However, the molecular mechanisms of plant lodging resistance
      remain largely unclear, especially in maize. We report here that the expression
      of ZmmiR528, a monocot-specific microRNA, is induced by N luxury but reduced by N
      deficiency. We show by the thioacidolysis and acetyl bromide analysis that N
      luxury significantly reduces the generation of H, G, and S monomers of the lignin
      as well as its total content in maize shoots. We further demonstrate that
      ZmLACCASE3 (ZmLAC3) and ZmLACCASE5 (ZmLAC5), which encode the copper-containing
      laccases, are the targets of ZmmiR528. In situ hybridization showed that ZmmiR528
      is mainly expressed in maize vascular tissues. Knockdown of ZmmiR528 or
      overexpression of ZmLAC3 significantly increased the lignin content and rind
      penetrometer resistance of maize stems. In contrast, transgenic maize plants
      overexpressing ZmmiR528 had reduced lignin content and rind penetrometer
      resistance and were prone to lodging under N-luxury conditions. RNA-sequencing
      analysis revealed that ZmPAL7 and ZmPAL8 are upregulated in transgenic maize
      lines downregulating ZmmiR528. Under N-luxury conditions, the expression levels
      of ZmPALs were much higher in ZmmiR528-knockdown lines than in the wild type and
      transgenic maize lines overexpressing ZmmiR528. Taken together, these results
      indicate that, by regulating the expression of ZmLAC3 and ZmLAC5, ZmmiR528
      affects maize lodging resistance under N-luxury conditions.

PMID- 29597010
TI  - Boston keratoprosthesis type 1 for limbal stem cell deficiency after severe
      chemical corneal injury: A systematic review.
AB  - PURPOSE: To systematically review the published literature on outcomes of Boston
      keratoprosthesis type 1 for the treatment of limbal stem cell deficiency
      secondary to severe chemical corneal injury. METHODS: Literature searches were
      conducted in MEDLINE (Ovid), Embase, Web of Science, and the Cochrane Central
      Register. The main outcome measures assessed were the proportion of eyes with
      best-corrected visual acuity (BCVA) >= 20/200 and the proportion retaining their
      original keratoprosthesis, both at the last recorded visit. RESULTS: We
      identified 9 reports in which outcomes of Boston keratoprosthesis type I
      implantation after severe chemical injury could be determined, encompassing a
      total of 106 eyes of 100 patients. There were no randomized controlled studies.
      The median pre-operative BCVA was hand motion. Vision improved to >=20/200 in
      99/106 (93.4%) eyes after implantation. With a mean follow-up of 24.99 +/- 14
      months, 68/106 (64.1%) eyes retained BCVA >= 20/200 at the last examination.
      Therefore, 68/99 (68.7%) of those who improved to > 20/200 maintained at least
      this acuity. The originally implanted device was retained in 88/99 (88.9%)
      recipients for whom retention was reported. The mean time to failure was 22.36 +/
      17.2 months. Glaucomatous optic neuropathy was the most common cause for BCVA
      <20/200 in eyes that retained the keratoprosthesis (18/27, 66.7%).. CONCLUSIONS:
      Implantation of a Boston keratoprosthesis type I in eyes with corneal blindness
      after severe chemical ocular injury leads to functional vision in the majority of
      recipients. Evidence was limited by variability in outcome reporting and an
      absence of controlled studies..

PMID- 29597011
TI  - Quantitative multiplexed profiling of Penicillium funiculosum secretome grown on
      polymeric cellulase inducers and glucose.
AB  - : Filamentous fungi respond to the need to secure utilisable carbon from their
      growth milieu by secreting unique extracellular proteins depending upon the types
      of polymeric substrates. We have here profiled the variations in the secretome
      pattern of a non-model hypercellulolytic fungus - Penicillium funiculosum, grown
      in minimal media containing four different polymeric cellulase inducers, i.e.,
      Avicel, wheat bran, ammonium-pretreated wheat straw and Avicel & wheat bran, and
      glucose over its early and late log phases of growth. Of the 137 secreted
      proteins validated at 1% FDR, we identified the quantified proteins in three
      clusters as early, persistently or lately expressed. The type of carbon substrate
      present in the culture media significantly affected the levels of cellulolytic
      enzymes expression by the fungus. The top abundant proteins quantified in the
      secretome for Avicel and wheat bran were cellobiohydrolaseI [GH7-CBM1],
      cellobiohydrolaseII [GH6-CBM1], beta-glucosidase [GH3], arabinofuranosidase
      [GH51] and beta-xylosidase [GH3], with bicupin being highest in case of wheat
      straw. Our results further suggested that the fungus secreted the extracellular
      proteins in waves, such that the initial responders act to hydrolyse the
      composite substrates in the culture environment before the second wave of
      proteins which tend to be more tailored to the specific substrate in the
      cultivating media. BIOLOGICAL SIGNIFICANCE: In this article, we have
      comprehensively examined the dynamics of the secretome of a non-model
      hypercellulolytic fungus produced in response to model and composite cellulase
      inducers. Our study has provided additional insights into how the fungus enzyme
      machinery responds to the presence of different polymeric cellulase inducers over
      the two different growth phases (early growth and late growth phase). The
      comprehensive typing and quantification of the different proteins present in the
      secretomes of the cellulolytic fungal strains in response to diverse nutrient
      sources hold many prospects in understanding the fungus unique enzyme machinery
      and dynamics for the downstream biotechnological applications.

PMID- 29597012
TI  - Differential expression of gonadotropin and estrogen receptors and oocyte
      cytology during follicular maturation associated with egg viability in European
      eel (Anguilla anguilla).
AB  - In captivity, oogenesis and ovarian follicle maturation in European eel can be
      induced experimentally using hormonal therapy. The follicle's ability to respond
      effectively to the induction of maturation and ovulation, resulting in viable
      eggs, depends on the oocyte stage at the time of induction. We hypothesized that
      variation in the expression of key hormone receptors in the ovary and size of
      oocyte lipid droplets are associated with changes in oocyte stage. Thus, we
      induced ovarian follicle maturation using a priming dose of fish pituitary
      extract followed by the administration of a 17alpha, 20beta-dihydroxy-4-pregnen-3
      one (DHP) injection. Females were then strip-spawned, the eggs were fertilized in
      vitro, incubated and larval survival was recorded at 3 days post hatch (dph). The
      expression of gonadotropin receptors (fshr, lhcgr1 and lhcgr2) and estrogen
      receptors (esr1, esr2a, esr2b, gpera and gperb) was quantified and the size of
      oocyte lipid droplets measured. Larval survival at 3 dph was used to
      differentiate high- and low-quality egg batches. Results showed significantly
      higher abundance of lhcgr1 and esr2a at priming for high-quality egg batches
      whereas fshr and gperb transcripts were significantly higher at DHP injection for
      low-quality egg batches. Therefore, high levels of lhcgr1 and esr2a may be
      important for attaining follicular maturational competence, while high fshr and
      gperb mRNA levels may indicate inadequate maturational competence. Furthermore,
      lipid droplet size at DHP and in ovulated eggs was significantly smaller in high
      quality egg batches than in low-quality, which indicates that droplet size may be
      a useful marker of follicular maturational stage.

PMID- 29597013
TI  - A new telemetry-based system for assessing cardiovascular function in group
      housed large animals. Taking the 3Rs to a new level with the evaluation of remote
      measurement via cloud data transmission.
AB  - INTRODUCTION: A newly developed total implant telemetry system for cardiovascular
      (CV), electrophysiological and body temperature measurement was evaluated. A
      cloud-based transmission of the physiological signals allowed an assessment of
      the quality of the physiological signals despite the physical separation between
      the instrumented animals and the evaluating home laboratory. The new system is
      intended to be used for safety pharmacological evaluations of drug candidates in
      various species. METHODS: Two female minipigs, 6 Labrador-mixed breed dogs and 4
      female Cynomolgus monkeys were instrumented with a newly developed total implant
      system (TSE SYSTEMS). The implants feature a microprocessor, internal memory (1
      GB), 2 solid state pressure-tipped catheters, amplifiers and a radio transmitter.
      Sampling rates for each measurement can be selected within a range between 0.1
      and 1 kHz. Biological signals are selected in a programmable fashion on a session
      by-session basis according to a user-defined protocol. The pressure sensors are
      at the tip of an electrical lead having a length customized to each species. Core
      temperature measurement and activity monitoring (3D accelerometer) are included
      in the system. Digital transmission range using a single antenna is 5 m with up
      to 16 animals held together and monitored simultaneously. The range can be
      expanded with more antennas in an array coupled to a single receiver. The
      antenna/receiver station consists of a single USB powered mobile unit connected
      to a PC or laptop. The battery life provides 110 days of continuous recording.
      The dogs and minipigs were instrumented and monitored in Germany. A novel cloud
      based data transmission system was developed to monitor the physiological signals
      in real-time from the Cynomolgus monkeys, still kept in Mauritius, from the data
      evaluation laboratory in Germany. After recovery from the surgical implantation,
      aortic pressure (AP), left ventricular pressure (LVP), ECG and body temperature
      were recorded for 24 hr monitoring sessions in all animals. Additionally,
      moxifloxacin (10, 30 and 100 mg/kg) was tested in the dog model using a modified
      Latin square cross-over study design. RESULTS: The implant was well tolerated and
      the animals recovered rapidly from the implantation procedure. Excellent signal
      quality was obtained and stable hemodynamic and electrophysiological parameters
      could be measured, with little signal artefact or drop-out, over 24 h in each
      species. After oral dosing of moxifloxacin to the dogs, a substantial, dose
      dependent increase in the QT-interval duration could be shown, as anticipated for
      this agent. Cloud-based data acquisition from the animals in Mauritius and the
      data evaluation lab in Germany worked well. CONCLUSION: This new CV telemetry
      system provides a novel alternative to fluid-filled catheter telemetry systems
      and the coupling to a cloud-based data transmission allows for flexibility in the
      location of the instrumented animals and data acquisition and the location of the
      site for data analysis. For the first time it is technically feasible to conduct
      a CV safety pharmacology study in Cynomolgus monkeys without having to ship them
      long distances to the home laboratory.

PMID- 29597014
TI  - Fatigue in Parkinson's disease: Metric properties of the fatigue impact scale for
      daily use (D-FIS), and its impact on quality of life.
AB  - OBJECTIVE: In Parkinson's disease patients, fatigue is a disabling non-motor
      symptom whose prevalence ranges from 28% to 58%. The Fatigue Impact Scale for
      Daily Use (D-FIS), one of the various scales for quantifying fatigue. The aim of
      our study was to analyze the metric properties of the D-FIS in PD subjects and
      assess the impact of fatigue on their quality of life. PATIENTS AND METHODS: The
      cohort in this study was comprised of 211 consecutive patients with a PD
      diagnosis regularly followed up at the Movement Disorders Unit of the Neurology
      Department at Carlos Andrade Marin Hospital (HCAM) in Quito, Ecuador, according
      to the United Kingdom PD Society Brain Bank criteria. Data Quality,
      Acceptability, Reliability, Stability (test-retest), Validity and Multiple linear
      regression analysis were determined. RESULTS: The final sample consisted of 138
      men (65.4%) and 73 women. Forty-six percent of these (98 patients) were in stage
      II of H&Y. We obtained a Cronbach's alpha value of 0.912 and an ICC value of
      0.79. D-FIS was strongly correlated with depression (Spearman rho [Srho] 0.60),
      anxiety (Srho 0.59), quality of life (Srho 0.67), and non-motor symptoms (Srho
      0.66). The scale's discriminant validity, assessed among the different stages of
      H&Y by the Kruskal-Wallis test, showed major significance (X2 = 23.183, p <=
      0.001). In the Multiple linear regression study, the resulting model proves that
      fatigue has a determining effect on quality of life. CONCLUSIONS: The D-FIS has
      good metric properties and demonstrates that fatigue significantly affects PD
      patients' quality of life and that its impact is independent from that of
      anxiety, depression, and sleep disorders.

PMID- 29597015
TI  - Evaluation of Olfactory Outcome After Frontolateral Approach for Treatment of
      Suprasellar Tumors.
AB  - OBJECTIVE: We present the findings of our prospective study assessing olfactory
      function outcome in patients undergoing a frontolateral approach for the
      resection of suprasellar lesions. METHODS: Eighteen consecutive patients (7
      females, 11 males) surgically treated at our institute for suprasellar tumors
      were included in this prospective study. Olfactory function was evaluated at the
      admission and 14 days after the surgery using the standard 12-item "Sniffin'
      Sticks" screening (SSS) test. The olfactory outcome was correlated to the
      following variables: tumor type, size, consistency, and extent of vertical and
      lateral growth. RESULTS: Preoperative and postoperative SSS test mean values
      were, respectively, 9.11 and 8.72 (not significant: P = 0.274). In only 1 case
      (5%), with larger suprasellar extension, the difference between preoperative and
      postoperative SSS was >=3 (reduction of 5 points). At the subjective evaluation,
      no patient stated a deficit in smelling. CONCLUSION: The frontolateral craniotomy
      is a minimally invasive route to treat suprasellar tumors and has a low approach
      related morbidity. It allows tumor resection with low risk for the olfactory
      function. A risk factor for postoperative olfactory deficit could be significant
      brain retraction.

PMID- 29597016
TI  - A Cohort Study of the Natural History of Odontoid Pseudoarthrosis Managed
      Nonoperatively in Elderly Patients.
AB  - OBJECTIVE: Although the primary goal of treatment of type II odontoid fracture is
      bony union, some advocate continued nonsurgical management of minimally
      symptomatic older patients who have fibrous union or minimal fracture motion. The
      risk of this strategy is unknown. We reviewed our long-term outcomes after dens
      nonunion to define the natural history of Type II odontoid fractures in elderly
      patients managed nonoperatively. METHODS: A retrospective chart review of 50
      consecutive adults aged 65 or older with Type II odontoid fracture initially
      managed nonsurgically from 1998 to 2012 at a single tertiary care institution was
      conducted. Particular attention was paid to patients who had orthosis removal
      despite absent bony fusion. Patients were contacted prospectively by telephone
      and followed until death, surgical intervention, or last known contact. RESULTS:
      Fifty patients initially were managed nonsurgically; of these, 21 (42.0%)
      proceeded to bony fusion, 3 (6%) underwent delayed surgery for persistent
      instability, and 26 (52%) had orthosis removal despite the lack of solid
      arthrodesis on imaging. The last group had a median follow-up of 25 months (range
      4-158 months), with 20 of 26 (76.9%) followed until death. Of these patients, 1
      patient developed progressive quadriplegia and dysphagia 11 months after initial
      injury. Compared with patients with spontaneous union, patients with nonunion had
      shorter life expectancy, despite no significant differences between the groups
      with respect to age, sex, injury mechanism, radiographic variables, or follow-up
      duration. CONCLUSIONS: Orthosis removal despite fracture nonunion may be
      reasonable in elderly patients with Type II dens fractures.

PMID- 29597017
TI  - Enlarging Temporal Arachnoid Cyst Extending Inside the Sphenoid Sinus.
AB  - BACKGROUND: Cerebral arachnoid cysts that eroded the skull base and extended into
      the paranasal sinus are very rare with only a few cases reported. CASE
      DESCRIPTION: A 71-year-old woman with history of headache for 4 years was
      evaluated because of an enlarging right temporal cystic lesion with evidence of
      resorption of the greater wing of the sphenoid bone and a fluid-filled sphenoid
      sinus. For 3 years, the cerebral cyst remained stable and minimally symptomatic.
      On her last magnetic resonance imaging, the cyst enlarged and perilesional edema
      was identified. The patient was treated with an open intracranial approach to
      explore the cyst. An arachnoid cyst was found which extended into the sphenoid
      sinus through a defect in the temporal fossa floor. The skull base defect was
      repaired using a muscle plug and fibrin sealant to obliterate the dural and bony
      defect. The arachnoid cyst was fenestrated to the basal cisterns. CONCLUSIONS:
      Cerebral arachnoid cysts extending into the paranasal sinuses are very rare
      presenting mostly with rhinorrhea and nasal symptoms. Patients with neurologic
      symptoms may need intracranial surgery to fenestrate the cyst. Obliteration of
      the fistula into the paranasal sinus is essential to prevent further
      complications.

PMID- 29597018
TI  - Rare Event Captured with Intracranial Pressure Monitor: Malignant Spike in
      Intracranial Pressure During Delayed Chest Closure in Heart-Transplant Patient
      with Ischemic Stroke.
AB  - BACKGROUND: Patients with open chest wounds, either related to trauma or
      cardiothoracic procedures, are subjected to significant physiologic alterations
      when undergoing chest wound closure. Sudden increased intrathoracic pressure at
      closure decreases venous return from the brain to the heart; consequently the
      total blood volume in the ridged skull increases, resulting in increased
      intracranial pressure (ICP). Patients with intact cerebrovascular autoregulation
      can compensate for these sudden changes by adjusting cerebral blood flow to
      maintain physiologic ICP. In cases where the autoregulatory mechanisms are
      compromised, such as stroke or trauma, the ICP can become pathologically
      elevated. If the patient does not have an ICP monitor, the spike in ICP can go
      unrecognized, compromising cerebral perfusion pressure and resulting in increased
      morbidity and mortality. CASE DESCRIPTION: Herein we describe a case of
      pathologic elevations in ICP captured with an ICP monitor at the time of chest
      wound closure in a patient with delayed chest wound closure after orthotopic
      heart transplant and comorbid embolic stroke. CONCLUSIONS: This case report
      demonstrates the potential utility of ICP monitoring in patients with impaired
      cerebrovascular autoregulation with open and manipulated chest wounds from
      transplant or trauma.

PMID- 29597019
TI  - Quantitative Evaluation of Compressed L4-5 and S1 Nerve Roots of Lumbar Disc
      Herniation Patients by Diffusion Tensor Imaging and Fiber Tractography.
AB  - OBJECTIVE: To delineate fractional anisotropy (FA) and apparent diffusion
      coefficient (ADC) values of compressed nerve roots in patients with lumbar disc
      herniation by diffusion tensor imaging and fiber bundle tracing and investigate
      the relationship between FA and ADC values and Swiss Spinal Stenosis
      Questionnaire and visual analog scale scores. METHODS: Twenty patients with
      lumbar disc herniation and 20 age- and sex-matched healthy volunteers were
      assessed using the Swiss Spinal Stenosis Questionnaire and visual analog scale.
      All subjects underwent conventional sagittal T1-weighted and T2-weighted magnetic
      resonance imaging, axial T2-weighted imaging, and diffusion tensor imaging and
      fiber tractography. RESULTS: In 20 patients with lumbar disc herniation, there
      were 31 nerve roots involved (9/31 L4, 15/31 L5, and 7/31 S1). Mean Swiss Spinal
      Stenosis Questionnaire scores of patients were 53.55% +/- 11.91%, and mean visual
      analog scale scores were 5.96 +/- 1.64. FA values of lumbar nerve roots were
      0.332 +/- 0.014 in healthy volunteers. FA values of compressed lumbar nerve roots
      were 0.251 +/- 0.022, significantly lower than FA values of contralateral
      noncompressed nerve roots and lumbar nerve roots of healthy volunteers. ADC
      values of lumbar nerve roots were 1.763 +/- 0.075 in healthy volunteers. ADC
      values of compressed lumbar nerve roots were 2.090 +/- 0.078, significantly
      higher than ADC values of contralateral noncompressed nerve roots and lumbar
      nerve roots of healthy volunteers. CONCLUSIONS: Fiber tractography is capable of
      delineating microstructural changes of lumbosacral nerve roots, and radiculopathy
      in lumbar disc herniation is associated with significant changes in FA and ADC
      values.

PMID- 29597021
TI  - Mapping of Arithmetic Processing by Navigated Repetitive Transcranial Magnetic
      Stimulation in Patients with Parietal Brain Tumors and Correlation with
      Postoperative Outcome.
AB  - BACKGROUND: Preserving functionality is important during neurosurgical resection
      of brain tumors. Specialized centers also map further brain functions apart from
      motor and language functions, such as arithmetic processing (AP). The mapping of
      AP by navigated repetitive transcranial magnetic stimulation (nrTMS) in healthy
      volunteers has been reported. OBJECTIVE: The present study aimed to correlate the
      results of mapping AP with functional patient outcomes. METHODS: We included 26
      patients with parietal brain tumors. Because of preoperative impairment of AP,
      mapping was not possible in 8 patients (31%). We stimulated 52 cortical sites by
      nrTMS while patients performed a calculation task. Preoperatively and
      postoperatively, patients underwent a standardized number-processing and
      calculation test (NPCT). Tumor resection was blinded to nrTMS results, and the
      change in NPCT performance was correlated to resected AP-positive spots as
      identified by nrTMS. RESULTS: The resection of AP-positive sites correlated with
      a worsening of the postoperative NPCT result in 12 cases. In 3 cases, no AP
      positive sites were resected and the postoperative NPCT result was similar to or
      better than preoperatively. Also, in 3 cases, the postoperative NPCT result was
      better than preoperatively, although AP-positive sites were resected.
      CONCLUSIONS: Despite presenting only a few cases, nrTMS might be a useful tool
      for preoperative mapping of AP. However, the reliability of the present results
      has to be evaluated in a larger series and by intraoperative mapping data.

PMID- 29597022
TI  - Design and preparation of bi-functionalized short-chain modified zwitterionic
      nanoparticles.
AB  - : An ideal nanomaterial for use in the bio-medical field should have a
      distinctive surface capable of effectively preventing nonspecific protein
      adsorption and identifying target bio-molecules. Recently, the short-chain
      zwitterion strategy has been suggested as a simple and novel approach to create
      outstanding anti-fouling surfaces. In this paper, the carboxyl end group of short
      chain zwitterion-coated silica nanoparticles (SiO2-ZWS) was found to be difficult
      to functionalize via a conventional EDC/NHS strategy due to its rapid hydrolysis
      side-reactions. Hence, a series of bi-functionalized silica nanoparticles (SiO2
      ZWS/COOH) were designed and prepared by controlling the molar ratio of 3
      aminopropyltriethoxysilane (APTES) to short-chain zwitterionic organosiloxane
      (ZWS) in order to achieve above goal. The synthesized SiO2-ZWS/COOH had similar
      excellent anti-fouling properties compared with SiO2-ZWS, even in 50% fetal
      bovine serum characterized by DLS and turbidimetric titration. Subsequently, SiO2
      ZWS/COOH5/1 was chosen as a representative and then demonstrated higher detection
      signal intensity and more superior signal-to-noise ratios compare with the pure
      SiO2-COOH when they were used as a bio-carrier for chemiluminescence enzyme
      immunoassay (CLEIA). These unique bi-functionalized silica nanoparticles have
      many potential applications in the diagnostic and therapeutic fields. STATEMENT
      OF SIGNIFICANCE: Reducing nonspecific protein adsorption and enhancing the
      immobilized efficiency of specific bio-probes are two of the most important
      issues for bio-carriers, particularly for a nanoparticle based bio-carrier.
      Herein, we designed and prepared a bi-functional nanoparticle with anti-fouling
      property and bio conjugation capacity for further bioassay by improving the short
      chain zwitterionic modification strategy we have proposed previously. The
      heterogeneous surface of this nanoparticle showed effective anti-fouling
      properties both in model protein solutions and fetal bovine serum (FBS). The
      modified nanoparticles can also be successfully functionalized with a specific
      antibody for CLEIA assay with a prominent bio-detection performance even in 50%
      FBS. In this paper, we also investigated an unexpectedly fast hydrolysis behavior
      of NHS-activated carboxylic groups within the pure short-chain zwitterionic
      molecule that led to no protein binding in the short-chain zwitterion modified
      nanoparticle. Our findings pave a new way for the designing of high performance
      bio-carriers, demonstrating their strong potential as a robust platform for
      diagnosis and therapy.

PMID- 29597020
TI  - A Novel Knotless Barbed Suture Technique for Traumatic Thoracolumbar Fracture in
      Posterior Surgery.
AB  - BACKGROUND: Surgical wound closure directly influences spinal surgical efficiency
      and several postoperative complications. The traditional suture technique is time
      consuming and associated with greater rates of complications. Bidirectional
      absorbable barbed sutures seem to compensate for some of the limitations of
      traditional suture; however, they rarely are reported in spinal surgery. We
      designed a novel suture technique for use in thoracolumbar spinal surgery.
      METHODS: The data of 189 patients with traumatic thoracolumbar fractures were
      analyzed between bidirectional barbed suture closure and traditional interrupted
      suture closure. Data of operative time, wound closure time, length of incision,
      intraoperative blood loss, complications of wound dehiscence and postoperative
      hematoma, cost, and neurologic status were collected. RESULTS: No significant
      differences were observed in the baseline demographics of included patients.
      Compared with the traditional suturing group, the barbed sutures decreased the
      mean operative time (P = 0.037), suture time (P < 0.01), and mean suturing time
      (P < 0.01) significantly, although no statistically significant differences were
      found in blood loss (P = 0.724) and neurologic functional scores (preoperative: P
      = 0.901; 3 months after surgery: P = 0.208; final follow-up assessments: P =
      0.163), and no statistically significant differences were found in rates of
      postoperative infection, hematoma, and wound dehiscence. CONCLUSIONS: Our
      findings suggest that the novel knotless barbed suture has comparable strength to
      traditional sutures, with the advantage of less suturing time. It is an
      efficient, safe technique, and alternative choice for patients with thoracolumbar
      fracture after posterior surgery.

PMID- 29597023
TI  - Impact of nitinol stent surface processing on in-vivo nickel release and
      biological response.
AB  - : Although nitinol is widely used in percutaneous cardiovascular interventions, a
      causal relationship between nickel released from implanted cardiovascular devices
      and adverse systemic or local biological responses has not been established. The
      objective of this study was to investigate the relationship between nitinol
      surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents
      manufactured using select surface treatments were implanted into the iliac
      arteries of minipigs for 6 months. Clinical chemistry profile, complete blood
      count, serum and urine nickel analyses were performed periodically during the
      implantation period. After explant, stented arteries were either digested and
      analyzed for local nickel concentration or fixed and sectioned for
      histopathological analysis of stenosis and inflammation within the artery. The
      results indicated that markers for liver and kidney function were not different
      than baseline values throughout 180 days of implantation regardless of surface
      finish. In addition, white blood cell, red blood cell, and platelet counts were
      similar to baseline values for all surface finishes. Systemic nickel
      concentrations in serum and urine were not significantly different between
      processing groups and comparable to baseline values during 180 days of
      implantation. However, stents with non-optimized surface finishing had
      significantly greater nickel levels in the surrounding artery compared to
      polished stents. These stents had increased stenosis with potential for local
      inflammation compared to polished stents. These findings demonstrate that proper
      polishing of nitinol surfaces can reduce in-vivo nickel release locally, which
      may aid in minimizing adverse inflammatory reactions and restenosis. STATEMENT OF
      SIGNIFICANCE: Nitinol is a commonly used material in cardiovascular medical
      devices. However, relationships between nitinol surface finishing, in-vivo metal
      ion release, and adverse biological responses have yet to be established. We
      addressed this knowledge gap by implanting single and overlapped nitinol stents
      with different surface finishes to assess systemic impact on minipigs (i.e. serum
      and urine nickel levels, liver and kidney function, immune and blood count) over
      the 6 month implantation period. In addition, nickel levels and histopathology in
      stented arteries were analyzed on explant to determine relationships between
      surface processing and local adverse tissue reactions. The findings presented
      here highlight the importance of surface processing on in-vivo nickel release and
      subsequent impact on local biological response for nitinol implants.

PMID- 29597025
TI  - Stromal cell-derived factor-1alpha-encapsulated albumin/heparin nanoparticles for
      induced stem cell migration and intervertebral disc regeneration in vivo.
AB  - : Intervertebral disc (IVD) degeneration may cause many diseases and pain. Stem
      cell migration toward the site of IVD degeneration is a key factor for IVD
      regeneration. In the current study, we prepared albumin/heparin nanoparticles
      (BHNPs) as injectable carriers of stromal cell-derived factor-1alpha (SDF-1alpha,
      also known as C-X-C motif chemokine 12), a powerful chemoattractant for the
      homing of bone marrow resident mesenchymal stem cells (MSCs), for protection of
      the molecule against degradation for a sustained release. The NPs have relatively
      uniform small size, with a diameter of about 110 nm. The NPs possess a high
      loading capacity of SDF-1alpha with a sustained release profile. The bioactivity
      of the obtained BHNPs/SDF was then studied in vitro and in vivo. The BHNPs/SDF
      can induce migration of MSCs in a dose-dependent manner in vitro. After injected
      into the damaged disc, BHNPs/SDF induce much better regeneration of annulus
      fibrosus and nucleus pulposus, compared to SDF-1alpha and BHNPs alone, evidenced
      with better histological grade scores and higher expression of SOX9, Aggrecan,
      and Collagen type II at the level of both mRNA and protein. This study provides a
      simple nanoplatform to load SDF-1alpha and protect it against degradation, with
      potential application in inductive tissue regeneration in vivo. STATEMENT OF
      SIGNIFICANCE: Stem cell migration toward the site of IVD degeneration is a key
      event to promote IVD regeneration. In the current study, we prepared
      albumin/heparin nanoparticles (BHNPs) as injectable carriers to protect SDF
      1alpha against degradation and for the sustained release of the molecule. After
      injected into the damaged disc, BHNPs/SDF induced much better regeneration of
      IVD, compared to SDF-1alpha and BHNPs alone. This study provides a simple
      nanoplatform to load SDF-1alpha and protect it from degradation, with potential
      application in inductive tissue regeneration in vivo.

PMID- 29597024
TI  - Design of hydrogels to stabilize and enhance bone morphogenetic protein activity
      by heparin mimetics.
AB  - : Although bone morphogenetic protein-2 (BMP-2) is known to be the most potent
      stimulator available for bone formation, a major barrier to widespread clinical
      use is its inherent instability and absence of an adequate delivery system.
      Heparin is being widely used in controlled release systems due to its strong
      binding ability and protective effect for many growth factor proteins. In this
      work, we developed a hydrogel surface that can mimic heparin to stabilize BMP-2
      and to enhance osteogenesis by introducing heparin-mimicking sulfonated molecules
      such as poly-vinylsulfonic acid (PVSA) or poly-4-styrenesulfonic acid (PSS), into
      photo-crosslinkable hydrogel. Bioactivity of BMP-2 was well preserved in the
      presence of polysulfonates during exposure to various therapeutically relevant
      stressors. The heparin-mimicking sulfonated hydrogels were effective to bind BMP
      2 compared to unmodified MeGC hydrogel and significantly enhanced osteogenic
      differentiation of encapsulated bone marrow stromal cells (BMSCs) without the
      addition of exogenous BMP-2. The sulfonated hydrogels were effective in
      delivering exogenous BMP-2 with reduced initial burst and increased BMSCs
      osteogenesis induced by BMP-2. These findings suggest a novel hydrogel platform
      for sequestering and stabilizing BMP-2 to enhance osteoinductive activity in bone
      tissue engineering. STATEMENT OF SIGNIFICANCE: Although bone morphogenetic
      protein-2 (BMP-2) is believed to be the most potent cytokine for bone
      regeneration, its clinical applications require supraphysiological BMP dosage due
      to its intrinsic instability and fast enzymatic degradation, leading to worrisome
      side effects. This study demonstrates a novel hydrogel platform that mimics a
      natural protector of BMPs, heparin, to sequester and stabilize BMP-2 for
      increased osteoinductive signaling. This study will achieve the stabilization of
      BMPs with prolonged bioactivity by a synthetic heparin mimic that has not been
      examined previously. Moreover, the heparin mimetic hydrogel surface can augment
      endogenous BMP activity by sequestering and localizing the cell-produced BMPs.
      The additional knowledge gained from this study may suggest basis for future
      development of material-based therapeutics for tissue engineering.

PMID- 29597026
TI  - Adhesive gland transcriptomics uncovers a diversity of genes involved in glue
      formation in marine tube-building polychaetes.
AB  - : Tube-building sabellariid polychaetes are hermatypic organisms capable of
      forming vast reefs in highly turbulent marine habitats. Sabellariid worms
      assemble their tube by gluing together siliceous and calcareous clastic particles
      using a polyelectrolytic biocement. Here, we performed transcriptomic analyses to
      investigate the genes that are differentially expressed in the parathorax region,
      which contains the adhesive gland and tissues, from the rest of the body. We
      found a large number of candidate genes to be involved in the composition and
      formation of biocement in two species: Sabellaria alveolata and Phragmatopoma
      caudata. Our results indicate that the glue is likely to be composed by a large
      diversity of cement-related proteins, including Poly(S), GY-rich, H-repeat and
      miscellaneous categories. However, sequences divergence and differences in
      expression profiles between S. alveolata and P. caudata of cement-related
      proteins may reflect adaptation to the type of substratum used to build their
      tube, and/or to their habitat (temperate vs tropical, amplitude of pH, salinity
      ...). Related to the L-DOPA metabolic pathways and linked with the genes that
      were differentially expressed in the parathorax region, we found that tyrosinase
      and peroxidase gene families may have undergone independent expansion in the two
      Sabellariidae species investigated. Our data also reinforce the importance of
      protein modifications in cement formation. Altogether these new genomic resources
      help to identify novel transcripts encoding for cement-related proteins, but also
      important enzymes putatively involved in the chemistry of the adhesion process,
      such as kinases, and may correspond to new targets to develop biomimetic
      approaches. STATEMENTS OF SIGNIFICANCE: The diversity of bioadhesives elaborated
      by marine invertebrates is a tremendous source of inspiration to develop
      biomimetic approaches for biomedical and technical applications. Recent studies
      on the adhesion system of mussel, barnacle and sea star had highlighted the
      usefulness of high-throughput RNA sequencing in accelerating the development of
      biomimetic adhesives. Adhesion in sandcastle worms, which involves catechol and
      phosphate chemistries, polyelectrolyte complexes, supramolecular architectures,
      and a coacervation process, is a useful model to develop multipurpose wet
      adhesives. Using transcriptomic tools, we have explored the diversity of genes
      encoding for structural and catalytic proteins involved in cement formation of
      two sandcastle worm species, Sabellaria alveolata and Phragmatopoma caudata. The
      important genomic resource generated should help to design novel "blue"
      adhesives.

PMID- 29597027
TI  - Natural products with anti-aging potential: Affected targets and molecular
      mechanisms.
AB  - In recent years, there has been a great deal of attention toward the molecular
      machinery relevant to age-related progression controlled through the external
      intervention of polyphenols- an epigenetic-modulating diet. Natural products
      modulate cellular longevity through histone post-translational modification and
      can also induce the upregulation of autophagy, thus reducing the level of acetyl
      coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer
      related chronic inflammation is of great significance in aging. In line with
      this, SIRT1 protein levels are expanded in response to calorie restriction
      mimetics (CRM), in this way acting as autophagy inducers relevant to cancer
      prevention.

PMID- 29597028
TI  - Revisiting glycoside hydrolase family 20 beta-N-acetyl-d-hexosaminidases: Crystal
      structures, physiological substrates and specific inhibitors.
AB  - Glycoside hydrolase family 20 beta-N-acetyl-d-hexosaminidases (GH20s) catalyze
      the hydrolysis of glycosidic linkages in glycans, glycoproteins and glycolipids.
      The diverse substrates of GH20s account for their various roles in many important
      bioprocesses, such as glycoprotein modification, glycoconjugate metabolism,
      gamete recognition and chitin degradation in fungal cell walls and arthropod
      exoskeletons. Defects in human GH20s cause lysosomal storage diseases,
      Alzheimer's disease and osteoarthritis. Similarly, lower levels of GH20s arrest
      arthropod molting. Although GH20s are promising targets for drug and agrochemical
      development, designing bioactive molecules to target one specific enzyme is
      challenging because GH20s share a conserved catalytic mechanism. With the
      development of structural biology, the last two decades have witnessed a dramatic
      increase in crystallographic investigations of liganded and unliganded GH20s,
      providing core information for rational molecular designs. This critical review
      summarizes recent research advances in GH20s, with a focus on their structural
      basis of substrate specificity as well as on inhibitor design. As more crystal
      structures of targeted GH20s are determined and analyzed, dynamics of their
      catalysis and inhibition will also be elucidated, which will facilitate the
      development of new drugs, pesticides and agrochemicals.

PMID- 29597029
TI  - Dietary nutraceuticals as backbone for bone health.
AB  - Bone loss or osteoporosis, is a slow-progressing disease that results from
      dysregulation of pro-inflammatory cytokines. The FDA has approved number of drugs
      for bone loss prevention, nonetheless all are expensive and have multiple side
      effects. The nutraceuticals identified from dietary agents such as butein,
      cardamonin, coronarin D curcumin, diosgenin, embelin, gambogic acid, genistein,
      plumbagin, quercetin, reseveratrol, zerumbone and more, can modulate cell
      signaling pathways and reverse/slow down osteoporosis. Most of these
      nutraceuticals are inexpensive; show no side effect while still possessing anti
      inflammatory properties. This review provides various mechanisms of osteoporosis
      and how nutraceuticals can potentially prevent the bone loss.

PMID- 29597030
TI  - State of the art of aerobic granulation in continuous flow bioreactors.
AB  - In the wake of the success of aerobic granulation in sequential batch reactors
      (SBRs) for treating wastewater, attention is beginning to turn to continuous flow
      applications. This is a necessary step given the advantages of continuous flow
      treatment processes and the fact that the majority of full-scale wastewater
      treatment plants across the world are operated with aeration tanks and clarifiers
      in a continuous flow mode. As in SBRs, applying a selection pressure, based on
      differences in either settling velocity or the size of the biomass, is essential
      for successful granulation in continuous flow reactors (CFRs). CFRs employed for
      aerobic granulation come in multiple configurations, each with their own means of
      achieving such a selection pressure. Other factors, such as bioaugmentation and
      hydraulic shear force, also contribute to aerobic granulation to some extent.
      Besides the formation of aerobic granules, long-term stability of aerobic
      granules is also a critical issue to be addressed. Inorganic precipitation,
      special inocula, and various operational optimization strategies have been used
      to improve granule long-term structural integrity. Accumulated studies reviewed
      in this work demonstrate that aerobic granulation in CFRs is capable of removing
      a wide spectrum of contaminants and achieving properties generally comparable to
      those in SBRs. Despite the notable research progress made toward successful
      aerobic granulation in lab-scale CFRs, to the best of our knowledge, there are
      only three full-scale tests of the technique, two being seeded with anammox
      supported aerobic granules and the other with conventional aerobic granules; two
      other process alternatives are currently in development. Application of settling-
      or size-based selection pressures and feast/famine conditions are especially
      difficult to implement to these and similar mainstream systems. Future research
      efforts needs to be focused on the optimization of the granule-to-floc ratio,
      enhancement of granule activity, improvement of long-term granule stability, and
      a better understanding of aerobic granulation mechanisms in CFRs, especially in
      full-scale applications.

PMID- 29597031
TI  - Clinical, technological, and economic issues associated with developing new lung
      surfactant therapeutics.
AB  - Discovery of lung surfactant deficiency as a main cause of neonatal respiratory
      distress syndrome (NRDS) has influenced a steep increase in lung surfactant
      research. Although this has yielded impactful scientific discoveries, much of the
      basic research on lung surfactants has failed to translate into clinical
      practices. This is attributed to insufficient information covering the entire
      lung surfactant ecosystem, from the basic science to economics surrounding the
      development and clinical practices. In this manuscript, developments related to
      improving therapeutic lung surfactant as well as the degree of unmet need are
      analyzed from both technical and economic perspectives. Two potential
      opportunities are emphasized: (1) aerosolized lung surfactants to treat NRDS
      infants, and (2) synthetic lung surfactants for acute respiratory distress
      syndrome (ARDS) patients. Each has a modestly projected US market size of $120
      million and $4 billion, well enough to make up for the high development costs
      associated with investigational drug development. Both opportunities have been
      pursued in the past, but to date these attempts have met with no success mainly
      due to technical limitations. With the recent advancements in both fields,
      technology improvements have created opportunities to solve both decades-old
      problems.

PMID- 29597032
TI  - Current advanced therapy cell-based medicinal products for type-1-diabetes
      treatment.
AB  - In the XXI century diabetes mellitus has become one of the main threats to human
      health with higher incidence in regions such as Europe and North America. Type 1
      diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated
      destruction of insulin producing beta-cells located in the endocrine part of the
      pancreas, the islets of Langerhans. The administration of exogenous insulin
      through daily injections is the most prominent treatment for T1DM but its
      administration is frequently associated to failure in glucose metabolism control,
      finally leading to hyperglycemia episodes. Other approaches have been developed
      in the past decades, such as whole pancreas and islet allotransplantation, but
      they are restricted to patients who exhibit frequent episodes of hypoglycemia or
      renal failure because the lack of donors and islet survival. Moreover, patients
      transplanted with either whole pancreas or islets require of immune suppression
      to avoid the rejection of the transplant. Currently, advanced therapy medicinal
      products (ATMP), such as implantable devices, have been developed in order to
      reduce immune rejection response while increasing cell survival. To overcome
      these issues, ATMPs must promote vascularization, guaranteeing the nutritional
      contribution, while providing O2 until vasculature can surround the device.
      Moreover, it should help in the immune-protection to avoid acute and chronic
      rejection. The transplanted cells or islets should be embedded within
      biomaterials with tunable properties like injectability, stiffness and porosity
      mimicking natural ECM structural characteristics. And finally, an infinitive cell
      source that solves the donor scarcity should be found such as insulin producing
      cells derived from mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and
      induced pluripotent stem cells (iPSCs). Several companies have registered their
      ATMPs and future studies envision new prototypes. In this review, we will discuss
      the mechanisms and etiology of diabetes, comparing the clinical trials in the
      last decades in order to define the main characteristics for future ATMPs.

PMID- 29597033
TI  - Nevirapine-polycaprolactone crystalline inclusion complex as a potential long
      acting injectable solid form.
AB  - Nevirapine (NVP) is recommended by WHO as the antiretroviral treatment to prevent
      HIV passing from mother to child. However, the once-daily oral administration
      results in poor patient compliance, and a long-acting injectable form of NVP is
      desirable. Using single-crystal X-ray diffraction and other characterization
      methods, we demonstrated NVP can form crystalline inclusion complex (IC) with the
      biodegradable hydrophobic poly(epsilon-caprolactone) (PCL), and investigated the
      potential of the NVP-PCL IC microparticles as a long-acting injectable solid
      form. Compared with pure NVP crystals and NVP/polylactide microparticles, the NVP
      PCL IC crystals showed significantly decreased solubility and slower dissolution
      rate, making it more suitable to be developed to achieve sustained-release
      profiles. In addition, the NVP-PCL IC microparticles with an average diameter
      below 10 MUm can be conveniently prepared by spray drying and are found to be
      easily injectable through a 25G needle. These results demonstrated the
      possibility of using drug-polymer IC microparticles as long-acting injectable
      forms, providing a new approach to design sustained-release drug products.

PMID- 29597034
TI  - Microsuspension of fatty acid esters of entecavir for parenteral sustained
      delivery.
AB  - Entecavir (EV), an anti-viral agent for hepatitis B infection, should be
      administered under fasted state, as intestinal absorption of this hydrophilic
      compound is markedly decreased under post-prandial conditions. Herein, in order
      to improve therapeutic adherence, a parenteral sustained delivery system was
      constructed, by synthesizing water-insoluble ester prodrugs of the nucleotide
      analogous with fatty acids. EV-3-palmitate (named EV-P), exhibited the lowest
      solubility in phosphate buffered saline (pH 7.4, 1.1 MUg/ml), with extended
      release profile compared with EV, EV-3-myristate, and EV-3-stearate, was selected
      as a candidate to formulate drug suspension. The crystalline suspension was
      fabricated using anti-solvent crystallization technique, with a mean particle
      size of 7.7 MUm. After subcutaneous (SC) injection in beagle dogs (0.43 mg/kg as
      EV), the plasma concentrations of EV were markedly protracted with lowered
      maximum plasma concentration (Cmax, 4.7 ng/ml), extended time required to reach
      Cmax (Tmax, 9.0 days), and lengthened elimination half-life (T1/2, 129.3 h)
      compared with those after oral administration (0.0154 mg/kg, Cmax, 15.4 ng/ml;
      Tmax, 0.01 days; T1/2, 4.1 h). The systemic exposure of the lipidic prodrug was
      below 0.1% compared with that of EV following SC injection, denoting that EV-P
      was rapidly converted into the parent compound in blood. Therefore, SC delivery
      of EV-P microsuspension can be an alternative to oral EV therapy, offering
      prolonged pharmacokinetic profile after single injection.

PMID- 29597035
TI  - Partitioning of dispersed nanoparticles in a realistic nasal passage for targeted
      drug delivery.
AB  - The complex nasal structure poses obstacles for efficient nasal drug
      administration beyond the nasal valve, especially when targeting the olfactory
      region. This study numerically detailed the naturally inhaled nanoparticle
      transport process from the initial releasing locations to the final deposited
      sites using a realistic human nasal passage. Dispersed nanoparticles at different
      coronal cross-sections were partitioned into multiple groups according to their
      final deposited locations. Results showed inhaled nanoparticles are more likely
      to move along the septum. Olfactory deposited particles entered the nose through
      the inner superior corner of the nostril; the middle meatus deposited particles
      entered the nose through the top third of the nostril; the inferior deposited
      particles entered via the bottom floor regions of the nostril. Therefore,
      targeted nasal inhalation therapies that intentionally release therapeutic
      particles from these recognized regions at the nostril plane can considerably
      improve the resultant topical disposition doses. However, it remains challenging
      to completely prevent undesired particle depositions as particles coming from the
      same location may produce multiple-sites depositions due to partition
      overlapping. Nevertheless, the fraction of undesired particle deposition is
      anticipated to be reduced at a great extent compared to unplanned releasing
      approaches.

PMID- 29597036
TI  - Corrigendum to "Toxicology of octamethylcyclotetrasiloxane (D4)" [Toxicol. Lett.,
      279, October (Suppl. 1), 2-22].

PMID- 29597037
TI  - A new magnetic nanodiamond/graphene oxide hybrid (Fe3O4@ND@GO) material for pre
      concentration and sensitive determination of sildenafil in alleged herbal
      aphrodisiacs by HPLC-DAD system.
AB  - A sensitive analytical methodology was investigated to concentrate and determine
      of sildenafil citrate (SLC) present at trace level in herbal supplementary
      products. The proposed method is based on simple and sensitive pre-concentration
      of SLC by using magnetic solid phase extraction with new developed magnetic
      nanodiamond/graphene oxide hybrid (Fe3O4@ND@GO) material as a sorbent.
      Experimental variables affecting the extraction efficiency of SLC like; pH,
      sample volume, eluent type and volume, extraction time and amount of adsorbent
      were studied and optimized in detail. Determination of sildenafil citrate after
      magnetic solid phase extraction (MSPE) was carried out by HPLC-DAD system. The
      morphology, composition, and properties of the synthesized hybrid material was
      characterized by Fourier transform infrared spectrometry (FT-IR), Raman
      spectrometry (Raman), X-ray diffraction spectrometry (XRD), scanning electron
      microscopy (SEM), mapping photographs, zeta potential analyzer, and BET surface
      area analysis. Under optimized conditions, linear range was ranged from 5.00 to
      250.00 ng mL-1 with R2 of 0.9952. The limit of detection (LOD) was 1.49 ng mL-1
      and the recoveries at two spiked levels were ranged from 94.0 to 104.1% with the
      relative standard deviation (RSD) < 7.1% (n = 5). The enhancement factor (EF) was
      86.9. The results show that the combination MSPE with HPLC-DAD is a suitable and
      sensitive method for the determination of SLC in real samples.

PMID- 29597038
TI  - Simultaneous determination of eight bioactive compounds by LC-MS/MS and its
      application to the pharmacokinetics, liver first-pass effect, liver and brain
      distribution of orally administrated Gouteng-Baitouweng (GB) in rats.
AB  - Only focusing on the circulating levels is insufficient for the comprehensive
      understanding of the physiological disposition of herbal medicine in vivo.
      Therefore, we conducted the comprehensive investigation on the in vivo dynamic
      process of orally administrated Gouteng-Baitouweng (GB), a classical herb pair
      with anti-Parkinson potentials. Serving as the technical base, a sensitive and
      selective liquid chromatography-tandem mass spectrometry method was established
      and validated in the plasma, liver and brain, for simultaneous determination of
      five alkaloids (rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine
      and geissoschizine methyl ether) and three saponins (anemoside B4, anemoside A3
      and 23-hydroxybetulinic acid). Following liquid-liquid extraction, favorable
      chromatographic behaviors of eight analytes were obtained on Waters Xbrigde C18
      column within 13 min. This method elicited good linearity for the analytes at the
      concentration range of 0.3-1000 or 1.8-6000 ng/mL with favorable precision,
      accuracy and stability. Following oral administration of GB (25 g/kg) in rats,
      this method was applied to the quantitative analysis in the portal vein plasma,
      liver, systemic plasma, and brain. Consequently, anemoside B4 was of the highest
      exposure, followed by 23-hydroxybetulinic acid, anemoside A3, rhynchophylline and
      isocorynoxeine in vivo. Notably, three saponins were all observed with certain
      exposure in the brain, along with rhynchophylline at low levels. Besides, five
      alkaloids and 23-hydroxybetulinic acid underwent serious liver first-pass effect.
      Hence, the pharmacokinetics, liver first-pass effect, liver and brain
      distribution of ingredients in GB were clarified, which laid a solid foundation
      for interpreting its efficacy and safety.

PMID- 29597039
TI  - 3D-Image analysis of the impact of toothpaste abrasivity on the progression of
      simulated non-carious cervical lesions.
AB  - OBJECTIVES: To investigate the effect of toothpaste abrasive level on the
      progression of non-carious cervical lesions (NCCLs) using 3D-image subtraction.
      METHODS: Upper first premolars were allocated into seven groups (n = 16) of
      toothpaste/abrasive slurries: A-Zeodent113/5%, B-Zeodent124/10%, C
      Zeodent103/15%, D-Sensodyne Pronamel, E-Crest Cavity-Protection, F-Crest Pro
      Health-Whitening, and G-Deionized water (DIW). Teeth were mounted on acrylic
      blocks, and their root surfaces covered with acrylic resin, except for 2-mm near
      the cemento-enamel junction that was exposed to toothbrushing. Specimens were
      brushed with the slurries for 5000-, 15,000-, 35,000- and 65,000-strokes.
      Impressions were taken at baseline and after each brushing time, and then scanned
      by a 3D optical profilometer. Dentine volume loss was calculated by image
      subtraction software and subjected to mixed-model ANOVA and multiple comparison
      tests (alpha = 0.05). RESULTS: No significant differences among slurries were
      observed at 5000 and 15,000. At 35,000, F showed higher loss than all other
      groups except C, which did not differ from the others. At 65,000, F (4.19 +/-
      3.29 mm3) showed the highest loss, followed by C (2.33 +/- 1.47 mm3), which
      differed from all the other groups except B (1.85 +/- 0.91 mm3). Groups B, A
      (1.35 +/- 0.65 mm3), D (1.17 +/- 0.48 mm3), E (1.40 +/- 0.68 mm3) and G (1.12 +/-
      0.73 mm3) did not differ from each other. Groups F and C showed significant
      increase of volume loss starting at 35,000, while B, A, D and E only at 65,000;
      no increase loss was observed for G. CONCLUSIONS: 3D-image subtraction was able
      to quantify and differentiate tooth loss, but only at advanced stages. The
      progression of NCCLs was more evident and faster for highly abrasive slurries.
      CLINICAL SIGNIFICANCE: Upon root dentin exposure, brushing with lower abrasive
      dentifrices is advisable to reduce the risk for NCCLs development.

PMID- 29597040
TI  - Effect of shading technique and thickness on color stability and translucency of
      new generation translucent zirconia.
AB  - OBJECTIVE: To evaluate the effect of shading technique and thickness on the color
      stability and translucency of translucent zirconia after coffee thermocycling.
      METHODS: Specimens in different thicknesses (1; 1.5; 2 mm) (n = 4 for each
      thickness) were sectioned from translucent preshaded zirconia (Pre) and
      externally shaded zirconia (Ext). After sintering, specimens were glazed and
      subjected to 10,000 thermocycling in coffee solution. The color coordinates of
      specimens were measured with a spectroradiometer before and after coffee
      thermocyling. Color differences and relative translucency parameter (RTP) values
      were calculated with CIEDE2000 color difference and TPCIEDE2000 formulas. ANOVA
      was used to analyze the CIEDE2000 color difference and RTP values (alpha = 0.05).
      RESULTS: According to 2-way ANOVA, no significant effect of shading technique and
      thickness on the color difference values was found (P > .05). According to 3-way
      ANOVA, a significant interaction between the shading technique and thickness (P <
      .0001) was found for RTP. The RTP parameter decreased with the increase in the
      thickness. Ext specimens presented significantly higher RTP than Pre specimens (P
      < .0001), except for between Ext 1 mm and Pre 1 mm (P = .179). CONCLUSIONS:
      Neither shading technique nor tested thicknesses affected the color of
      translucent zirconia. Shading technique and thickness affected the RTP of
      translucent zirconia. The RTP was inversely affected with the thickness of the
      material. Externally shaded zirconia presented higher RTP than preshaded zirconia
      for specimens thicker than 1 mm. CLINICAL SIGNIFICANCE: Discoloration with coffee
      was insignificant for the tested translucent zirconia in tested thicknesses (1,
      1.5, 2 mm). When a translucent restoration is intended, thinner externally shaded
      translucent zirconia restorations should be preferred instead of preshaded
      translucent zirconia.

PMID- 29597041
TI  - Development of core-shell nanocarrier system for augmenting piperine cytotoxic
      activity against human brain cancer cell line.
AB  - Brain tumor has a low prognosis with only 15% survival rate (5 years after
      diagnosis). Many of the current therapeutics have limited activity due to their
      inability to cross the blood brain barrier which retards drug accumulation in
      tumor site and causes drug resistance. Piperine, a phytochemical drug with poor
      solubility, could be an alternative to current therapeutics after evading its
      solubility and permeability limitations. Piperine micellization was optimized to
      improve drug solubility. Positively charged trimethyl-chitosan was synthesized
      then electrostatically adsorbed onto piperine nanomicelles forming core-shell
      nanoparticles. Physicochemical and morphological characterizations, and in-vitro
      release were performed. Cytotoxicity on human brain cancer cell line (Hs683) was
      evaluated using IC50 determination, cell cycle arrest analysis, apoptosis and
      enzyme-linked immunosorbent assay. Optimum piperine-loaded core-shell
      nanoparticles were successfully fabricated with double-phase release model.
      Significant improvement in cytotoxicity than free drug was noted with increasing
      in G2/M-phase and pre-GI-phase population, apoptotic/necrotic rates and
      inhibition of CDK2a.

PMID- 29597042
TI  - Nasal dilation effects on olfactory deposition in unilateral and bi-directional
      deliveries: In vitro tests and numerical modeling.
AB  - The human nose can expand either actively or passively to increase airflow. Nasal
      dilation may alter drug delivery efficiencies in the nasal airway or olfactory
      region. However, the dosage enhancement from nasal dilations has not been
      quantified. The mechanisms underlying the dilation-induced deposition variation
      are also not clear. This study aims to quantify the nasal dilation effects on
      drug delivery in the nasal airway and olfactory region using in vitro tests and
      numerical analysis. Two variants of an existing normal nasal airway model were
      developed with different levels of airway dilation. Airway dimensions were
      quantified in terms of hydraulic diameter, cross-sectional area, and surface area
      to volume ratio. Sectional nose casts were prepared using a 3-D printer for
      visualizing deposition patterns and quantifying delivered dosages. A well
      validated computational fluid-particle dynamics (CFPD) model was utilized to
      understand the underlying mechanisms in the unilateral and bi-directional
      deliveries. In vitro tests show that nasal dilation lowered the total dosage in
      the nose but increased the dosage to the olfactory region in both the unilateral
      and bi-directional deliveries. Compared to the normal nose with unilateral
      delivery, nasal dilation enhanced the olfactory deposition by a factor of 2.2,
      while nasal dilatation with the bi-directional delivery increased by a factor of
      4. Complementary numerical analyses revealed the growth of a recirculation zone
      in the middle meatus of dilated noses, which induced lower pressure and increased
      ventilation to the upper nose. In bi-directional deliveries, a significantly
      higher fraction of airflow was ventilated to the upper airway in the outflow side
      of the nose and contributed to the elevated olfactory dosage. Nasal dilation in
      combination with the bi-directional delivery is recommended over the conventional
      unilateral method for olfactory targeting.

PMID- 29597043
TI  - Pegylated poly(anhydride) nanoparticles for oral delivery of docetaxel.
AB  - The aim of this work was to investigate the potential of pegylated
      poly(anhydride) nanoparticles to enhance the oral bioavailability of docetaxel
      (DTX). Nanoparticles were prepared after the incubation between the copolymer of
      methyl vinyl ether and maleic anhydride (Gantrez(r) AN), poly(ethylene glycol)
      (PEG2000 or PEG6000) and docetaxel (DTX). The oral administration of a single
      dose of pegylated nanoparticles to mice provided sustained and prolonged
      therapeutic plasma levels of docetaxel for up 48-72 h. In addition, the relative
      oral bioavailability of docetaxel was around 32%. The organ distribution studies
      revealed that docetaxel underwent a similar distribution when orally administered
      encapsulated in nanoparticles as when intravenously as Taxotere(r). This
      observation, with the fact that the clearance of docetaxel when loaded into the
      oral pegylated nanoparticles was found to be similar to that of intravenous
      formulation, suggests that docetaxel would be released at the epithelium surface
      and then absorbed to the circulation.

PMID- 29597044
TI  - Ex-vivo absorption study of lysine R-lipoate salt, a new pharmaceutical form of R
      ALA.
AB  - Alpha-lipoic acid (ALA) oral supplements were used in many pathologies associated
      with increased oxidative stress. Although only R-ALA is considered the
      biologically active form, R,S-ALA is used in therapeutic applications even
      showing poor water solubility. The aim of this work was to study the absorption
      and transport mechanism across the intestinal barrier of new R-ALA stable and
      water soluble form, consisting in the lysine R-ALA salt, in presence and absence
      of specific inhibitors of Na+/multivitamin (SMVT) and monocarboxylic acids (MCT).
      The absorption of a new ALA form was investigated at rat everted sacs in
      comparison with R-ALA, S-ALA, and R,S-ALA. Results showed that duodenum is the
      best portion of intestine for ALA forms absorption. The absorption percentage of
      R-ALA, S-ALA, R,S-ALA, and lysine R-ALA salt was 66%, 43%, 55%, and 70%,
      respectively. The modest effect of the SMVT inhibitor biotin demonstrated that
      this transporter system is not principally involved in the absorption of lysine R
      lipoate salt across the rat intestinal barrier. On the contrary, the MCT
      inhibitor octanoic acid significantly reduced the transport of this salt, whit an
      absorption decrease of R-ALA and lysine R-lipoate salt of 28% and 24%,
      respectively. Since the highest concentration of these inhibitors did not
      completely inhibit the absorption of lysine R-lipoate salt, other transport
      mechanisms probably operate for its intracellular delivery. The new form of ALA,
      lysine R-lipoate salt, was the most absorbed respect to the other ALA forms
      demonstrating that this compound is more suitable for oral administration. This
      new salt could represent a promising candidate for ALA oral supplementation.

PMID- 29597045
TI  - In situ nonlinear ultrasonic technique for monitoring microcracking in concrete
      subjected to creep and cyclic loading.
AB  - This research conducts in situ nonlinear ultrasonic (NLU) measurements for real
      time monitoring of load-induced damage in concrete. For the in situ measurements
      on a cylindrical specimen under sustained load, a previously developed second
      harmonic generation (SHG) technique with non-contact detection is adapted to a
      cylindrical specimen geometry. This new setup is validated by demonstrating that
      the measured nonlinear Rayleigh wave signals are equivalent to those in a flat
      half space, and thus the acoustic nonlinearity parameter, beta can be defined and
      interpreted in the same way. Both the acoustic nonlinearity parameter and strain
      are measured to quantitatively assess the early-age damage in a set of concrete
      specimens subjected to either 25 days of creep, or 11 cycles of cyclic loading at
      room temperature. The experimental results show that the acoustic nonlinearity
      parameter is sensitive to early-stage microcrack formation under both loading
      conditions - the measured beta can be directly linked to the accumulated
      microscale damage. This paper demonstrates the potential of NLU for the in situ
      monitoring of mechanical load-induced microscale damage in concrete components.

PMID- 29597046
TI  - Omnidirectional shear horizontal wave based tomography for damage detection in a
      metallic plate with the compensation for the transfer functions of transducer.
AB  - Guided-wave based damage detection for plates has been widely studied for
      structural health monitoring. Because most of the earlier studies used dispersive
      Lamb waves, substantial efforts had to be made to alleviate the dispersive and
      multi-modal nature of Lamb waves and the effect of surface conditions. In
      contrast, shear-horizontal (SH) waves have better propagation characteristics
      suitable for the detection of damages in plates, but SH waves have not been
      widely used due to the lack of efficient methods to generate and sense
      omnidirectional SH waves. The objective of this study is to construct diagnostic
      images of damaged plates by using omnidirectional SH waves with a special
      emphasis on the compensation of the frequency-dependence of the SH wave
      transducers. The compensation is necessary to have reliable diagnostic images
      because its frequency-dependent characteristics considerably can affect imaging
      quality if they are not considered. Consequently, simplified, yet effective,
      models representing the transfer functions of the omnidirectional SH wave
      magnetostrictive patch transducer (OSH-MPT) are developed in this paper. To
      visualize the position and shape of the structural damages in a metallic plate,
      the virtual time-reversal imaging method is used and two alternative techniques
      are considered to compensate for the effects of the transfer functions of
      transducers in the imaging processes. The imaging results after the compensation
      appear quite promising, suggesting that the omnidirectional SH wave based
      enhanced time-reversal imaging can be an efficient inspection method for plate
      structures.

PMID- 29597047
TI  - Nanomagnetic Modulation of Tumor Redox State.
AB  - Modulation of reactive oxygen and nitrogen species in a tumor could be exploited
      for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256
      carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe3O4
      nanoparticles combined with electromagnetic fields. Treatment using the magnetic
      nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest
      antitumor effect with the minimum growth factor 0.49 +/- 0.02 day-1 (compared to
      0.58 +/- 0.02 day-1 for conventional doxorubicin). Electron spin resonance
      spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an
      increase of 2.7 times of free iron (that promotes the formation of highly
      reactive oxygen species), using the nanodot with the largest hysteresis loop
      area, compared to conventional doxorubicin treatment as well as increases in
      ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the
      designed magnetic nanodots can modulate the tumor redox state. We discuss the
      implications of these results for cancer nanotherapy.

PMID- 29597048
TI  - Screening for canine transitional cell carcinoma (TCC) by SERS-based quantitative
      urine cytology.
AB  - Canine lower urinary tract neoplasia is a clinically important disease process
      that has high mortality due to late stage diagnosis and poorly durable response
      to treatment. Non-invasive diagnostic techniques (e.g. dipstick test, urine
      cytology) currently have poor diagnostic value, while more invasive tests (e.g.
      cystoscopy and biopsy) are costly and often require general anesthesia. We have
      developed and herein describe a quantitative cytological analysis method based on
      the use of surface-enhanced Raman spectroscopy (SERS), for identifying cancerous
      transitional cells in urine using SERS biotags (SBTs) carrying the peptide PLZ4
      (amino acid sequence cQDGRMGFc) that targets malignant transitional cells. By
      analyzing the ratio of the PLZ4-SBTs to an on board control we were able to show
      that transitional cells had significantly higher ratios (P < 0.05) in patients
      diagnosed with transitional cell carcinoma (TCC) than in healthy samples.

PMID- 29597049
TI  - Early Recognition of Heart Failure: A Call for Action.

PMID- 29597050
TI  - Did Frederic Chopin Die From Heart Failure?
AB  - On October 17, 1849, Poland's greatest composer, Frederic Chopin (1810-1849) died
      aged 39. His cause of death remains unknown. An investigation of the documental
      sources was performed to reconstruct the medical history of the artist. Since his
      earliest years, his life had been dominated by poor health. Recurrent episodes of
      cough, fever, headaches, lymphadenopathy- a series of symptoms that may be
      attributed to viral respiratory infections- manifested in his teens. Later in
      life, he had chest pain, hemoptysis, hematemesis, neuralgia, and arthralgia.
      Exhaustion and breathlessness characterized all his adult life. Coughing,
      choking, and edema of the legs and ankles manifested four months before his
      death. Several hypotheses ranging from cystic fibrosis to alpha-1 anti-trypsin
      deficiency and pulmonary tuberculosis have been proposed to explain Chopin's
      lifelong illness. We suggest that Chopin had dilated cardiomyopathy with
      consequent heart failure and cirrhosis that caused his death.

PMID- 29597051
TI  - Prognostic Impact of Pulmonary Artery Pulsatility Index (PAPi) in Patients With
      Advanced Heart Failure: Insights From the ESCAPE Trial.
AB  - BACKGROUND: The pulmonary artery pulsatility index (PAPi), defined as the ratio
      of pulmonary artery pulse pressure to right atrial pressure, emerged as a
      powerful predictor of right ventricular (RV) failure in patients with acute
      inferior myocardial infarction and those undergoing left ventricular assist
      device placement; however, its prognostic utility in the advanced heart failure
      population remains largely unknown. METHODS AND RESULTS: We comparatively
      analyzed PAPi with traditional indices of RV function including RV stroke work
      index and right atrial/pulmonary capillary wedge pressure ratio (RAP/PCWP) in the
      Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization
      Effectiveness trial. Median PAPi score was 2.35 in 190 patients. PAPi was
      significantly associated with clinical (jugular venous distention, ascites,
      edema), echocardiographic (right atrial size, vena cava size, tricuspid
      regurgitation velocity), and hemodynamic signs of RV failure (RAP, PCWP); all P <
      .05. In addition, PAPi was associated with the measures of left ventricular
      function, including ejection fraction, cardiac index, and PCWP (all P < .05). In
      Cox regression analysis, PAPi was an independent predictor of primary endpoint of
      death or hospitalization at 6 months (hazard ratio 0.91 [95% confidence interval
      0.84-0.99], P = .022), whereas RA pressure, RV stroke work index, or RA/PCWP were
      not. CONCLUSIONS: PAPi serves as a marker of RV dysfunction and strongly predicts
      adverse clinical events in patients with advanced heart failure. Incorporating
      PAPi into existing risk models can substantially improve patient selection for
      advanced therapies and clinical outcomes in this population.

PMID- 29597052
TI  - Risk of Ischemic Stroke in Patients Newly Diagnosed With Heart Failure: Focus on
      Patients Without Atrial Fibrillation.
AB  - BACKGROUND: Heart failure (HF) is associated with an incremental risk of stroke,
      but limited real-world data exist in patients with HF without atrial fibrillation
      (AF). OBJECTIVES: To quantify the incremental risk of ischemic stroke among newly
      diagnosed patients with HF and without AF. METHODS: Adults with HF and >=18
      months of enrollment before their index HF (ie, baseline period) were identified
      in Truven Health Analytics MarketScan Databases (January 2010-April 2015).
      Patients without AF during baseline and without an ischemic stroke within 14days
      of the index date were propensity score matched 1:1 to individuals with neither
      HF nor AF and observed for ischemic stroke. A similar analysis was performed for
      the overall HF population. Incidence rates were compared using incidence rate
      ratios between HF and non-HF cohorts; Kaplan-Meier analyses with log-rank tests
      were used to compare incidence rates over time. RESULTS: A total of 66,414
      patients with HF were identified, of which 52,005 did not have AF. Patients with
      HF without AF had significantly higher rates of ischemic stroke than patients
      without HF without AF during follow-up (incidence rate ratio 1.91 [95% confidence
      interval 1.75-2.09], P < .001). Ischemic stroke rates remained significantly
      higher for patients with HF over time among individuals without AF (P < .001 for
      log-rank test at 12, 24, and 36 months). Similar results were found for the
      overall HF population. CONCLUSIONS: Even in the absence of AF, patients with HF
      are at heightened risk of ischemic stroke compared with patients without HF.

PMID- 29597053
TI  - Associations With and Prognostic and Discriminatory Role of N-Terminal Pro-B-Type
      Natriuretic Peptide in Heart Failure With Preserved Versus Mid-range Versus
      Reduced Ejection Fraction.
AB  - BACKGROUND: The aim of this study was to characterize N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its
      prognostic and discriminatory role in heart failure with mid-range (HFmrEF)
      versus preserved (HFpEF) and reduced (HFrEF) ejection fraction. METHODS AND
      RESULTS: In 9847 outpatients with HFpEF (n = 1811; 18%), HFmrEF (n = 2122; 22%)
      and HFrEF (n = 5914; 60%) enrolled in the Swedish Heart Failure Registry, median
      NT-proBNP levels were 1428, 1540, and 2288 pg/mL, respectively. Many determinants
      of NT-proBNP differed by ejection fraction, with atrial fibrillation (AF) more
      important in HFmrEF and HFpEF, diabetes and hypertension in HFmrEF, and age and
      body mass index in HFrEF and HFmrEF, whereas renal function, New York Heart
      Association functional class, heart rate, and anemia were similar. Hazard ratios
      for death and death/HF hospitalization for NT-proBNP above the median ranged from
      1.48 to 2.00 and were greatest for HFmrEF and HFpEF. Areas under the receiver
      operating characteristic curve for death and death/HF hospitalization were
      greater in HFmrEF than in HFpEF and HFrEF and were reduced by AF in HFpEF and
      HFmrEF but not in HFrEF. CONCLUSIONS: In HFpEF and especially HFmrEF, NT-proBNP
      was more prognostic and discriminatory, but also more affected by confounders
      such as AF. These data support the use of NT-proBNP for eligibility, enrichment,
      and surrogate end points in HFpEF and HFmrEF trials, and suggest that cutoff
      levels for eligibility should be carefully tailored to comorbidity.

PMID- 29597054
TI  - Heart Failure Symptoms and Ecological Factors as Predictors of Chagas Disease
      Among Indigenous Communities in the Sierra Nevada de Santa Marta, Colombia.

PMID- 29597055
TI  - Hepatitis E virus in feral rabbits along a rural-urban transect in Central
      Germany.
AB  - Rabbit associated genotype 3 hepatitis E virus (HEV) strains were detected in
      feral, pet and farm rabbits in different parts of the world since 2009 and
      recently also in human patients. Here, we report a serological and molecular
      survey on 72 feral rabbits, collected along a rural-urban transect in and next to
      Frankfurt am Main, Central Germany. ELISA investigations revealed in 25 of 72
      (34.7%) animals HEV-specific antibodies. HEV derived RNA was detected in 18 of 72
      (25%) animals by reverse transcription-polymerase chain reaction assay. The
      complete genomes from two rabbitHEV-strains, one from a rural site and the other
      from an inner-city area, were generated by a combination of high-throughput
      sequencing, a primer walking approach and 5'- and 3'- rapid amplification of cDNA
      ends. Phylogenetic analysis of open reading frame (ORF)1-derived partial and
      complete ORF1/ORF2 concatenated coding sequences indicated their similarity to
      rabbit-associated HEV strains. The partial sequences revealed one cluster of
      closely-related rabbitHEV sequences from the urban trapping sites that is well
      separated from several clusters representing rabbitHEV sequences from rural
      trapping sites. The complete genome sequences of the two novel strains indicated
      similarities of 75.6-86.4% to the other 17 rabbitHEV sequences; the amino acid
      sequence identity of the concatenated ORF1/ORF2-encoded proteins reached 89.0
      93.1%. The detection of rabbitHEV in an inner-city area with a high human
      population density suggests a high risk of potential human infection with the
      zoonotic rabbitHEV, either by direct or indirect contact with infected animals.
      Therefore, future investigations on the occurrence and frequency of human
      infections with rabbitHEV are warranted in populations with different contact to
      rabbits.

PMID- 29597056
TI  - Emergence of multiple norovirus strains in Thailand, 2015-2017.
AB  - Norovirus is a major cause of non-bacterial acute gastroenteritis worldwide.
      Infection can be sporadic or result in widespread outbreaks. The surveillance of
      norovirus samples (n = 1591) obtained from patients with diarrhea in Thailand
      from January 2015 to February 2017 suggested that the predominance of norovirus
      GII.4 often seen in sporadic infection had been superseded by the emergence of
      GII.17. More recently, a sharp increase in acute gastroenteritis associated with
      norovirus GII.P16-GII.2 recombinant strain was observed at the end of 2016. Thus,
      previously rare norovirus strains and their recombinant derivatives may be more
      frequently responsible for future outbreaks.

PMID- 29597057
TI  - Relationship between incivility experiences and nursing professional values among
      nursing students: Moderating effects of coping strategies.
AB  - BACKGROUND: During clinical practice, nursing students develop their professional
      role and internalize the values of the nursing profession. Unfortunately, it also
      often exposes them uncivil behaviors from nurses. OBJECTIVES: To identify the
      relationship between incivility experiences and nursing professional values, and
      investigate the potential moderating effects of coping strategies in this
      relationship. DESIGN AND METHODS: This was a descriptive, cross-sectional study.
      Data were collected from 203 nursing students using questionnaires. The
      questionnaire comprised sections assessing participant characteristics,
      incivility experiences, coping strategies, and nursing professional values.
      Multiple regression analysis was used to identify the relationship between
      incivility experiences and nursing professional values, as well as the
      interaction effect of incivility experiences and coping strategies on nursing
      professional values. RESULTS: Incivility experiences were negatively related to
      nursing professional values. Furthermore, seeking support moderated the
      relationship between incivility experiences and nursing professional values. In
      other words, as incivility experiences increased, nursing students who used more
      seeking social support tended to have stronger nursing professional values than
      did those who used this coping strategy less. CONCLUSION: To improve the nursing
      professional values of nursing students, educators must inform nursing managers
      when nurses direct uncivil behaviors towards students. Educators should also
      listen to students' experiences, support them emotionally, and encourage students
      to engage in seeking social support.

PMID- 29597058
TI  - Structure of 3,6-dideoxy-3-[(R)-2-hydroxypropanoylamino]-D-galactose-containing O
      polysaccharide from marine bacterium Simiduia litorea KMM 9504T.
AB  - The O-polysaccharide was isolated from the lipopolysaccharide of a marine
      bacterium Simiduia litorea KMM 9504T and studied by chemical methods along with
      1D and 2D 1H and 13C NMR spectroscopy including 1H,1H-TOCSY, 1H,1H-COSY, 1H,1H
      ROESY, 1H,13C-HSQC and 1H,13C-HMBC experiments. The following new structure of
      the O-polysaccharide of S. litorea KMM 9504T containing D-galacturonamide, 2
      acetamido-2,6-dideoxy-D-glucose and 3,6-dideoxy-3-[(R)-2-hydroxypropanoylamino]-D
      galactose was established.

PMID- 29597059
TI  - Chemical application strategies to protect water quality.
AB  - Management of turfgrass on golf courses and athletic fields often involves
      application of plant protection products to maintain or enhance turfgrass health
      and performance. However, the transport of fertilizer and pesticides with runoff
      to adjacent surface waters can enhance algal blooms, promote eutrophication and
      may have negative impacts on sensitive aquatic organisms and ecosystems. Thus, we
      evaluated the effectiveness of chemical application setbacks to reduce the off
      site transport of chemicals with storm runoff. Experiments with water soluble
      tracer compounds confirmed an increase in application setback distance resulted
      in a significant increase in the volume of runoff measured before first off-site
      chemical detection, as well as a significant reduction in the total percentage of
      applied chemical transported with the storm runoff. For example, implementation
      of a 6.1 m application setback reduced the total percentage of an applied water
      soluble tracer by 43%, from 18.5% of applied to 10.5% of applied. Evaluation of
      chemographs revealed the efficacy of application setbacks could be observed with
      storms resulting in lesser (e.g. 100 L) and greater (e.g. > 300 L) quantities of
      runoff. Application setbacks offer turfgrass managers a mitigation approach that
      requires no additional resources or time inputs and may serve as an alternative
      practice when buffers are less appropriate for land management objectives or site
      conditions. Characterizing potential contamination of surface waters and
      developing strategies to safeguard water quality will help protect the
      environment and improve water resource security. This information is useful to
      grounds superintendents for designing chemical application strategies to maximize
      environmental stewardship. The data will also be useful to scientists and
      regulators working with chemical transport and risk models.

PMID- 29597060
TI  - Residue and distribution of triforine in different cultivars and fruit periods of
      watermelon under field conditions.
AB  - The dissipation of triforine in the immature and mature fruit periods was
      investigated under field conditions. Residue levels of triforine in watermelon
      were determined by gas chromatography with an electron capture detector (GC-ECD).
      The decline curves of triforine residues in the watermelon corresponded with
      first-order kinetics. The half-lives of triforine in Dark Belle and Shiny Boy
      were 2.10-2.57 days and 2.31-2.67 days respectively. Meanwhile, the half-lives of
      triforine in the immature and mature fruit periods were 1.69-2.04 days and 2.89
      3.85 days, respectively. In the terminal residue experiment, the terminal
      residues of triforine in the watermelon flesh and peel were below 0.01 mg/kg to
      0.05 mg/kg and 0.03 mg/kg to 0.36 mg/kg, respectively. The dissipation rates of
      triforine varied in different cultivars of watermelon, and even in the same
      cultivar, the half-lives of triforine significantly varied in the different fruit
      periods. Although triforine is a fungicide within the suction, the terminal
      residues in the peel and flesh were very significant.

PMID- 29597061
TI  - Individuality of masticatory performance and of masticatory muscle temporal
      parameters.
AB  - OBJECTIVE: Mammalian mastication serves to improve intra-oral food reduction.
      Insufficient food reduction creates potential swallowing problems, whereas over
      reduction may accelerate tooth wear and increase feeding time. Either extreme has
      consequences. The study's objectives were: (1) to study the relationship between
      food reduction, number of chews in a sequence, and chewing rate, (2) to study how
      controlling the number of chews and chewing rate variability affects food
      reduction, and (3) to assess how dentoskeletal morphological and
      electromyographical (EMG) characteristics impact food reduction. DESIGN: Twenty
      three healthy, fully-dentate adults chewed a standardized test food under three
      conditions: (1) no control, (2) number of chews controlled, and (3) number of
      chews and chewing rate controlled. EMG activity was sampled from masseter and
      temporalis muscles bilaterally. Demographic, occlusal contact area in maximum
      intercuspation, and cephalometric data were obtained. RESULTS: In uncontrolled
      conditions, food reduction and bout duration varied more than expected across
      subjects. Subjects with poor reduction under controlled conditions were those
      with poor reduction under uncontrolled conditions. Only occlusal contact area
      correlated with chewing performance under uncontrolled conditions. Chewing cycle
      duration, EMG burst duration, and EMG peak onset latency increased when the
      number of chews was restricted. EMG amplitude, a surrogate for bite force,
      increased in tasks controlling the number of chews and chewing rate. Chewing rate
      variability was difficult to diminish below individual-specific levels.
      CONCLUSIONS: Results: provided evidence that bite force, chewing rate, chewing
      performance and chewing bout duration reflected individual preferences. Future
      work will determine whether similar findings occur among other mammals.

PMID- 29597062
TI  - Expression and localization of phosphodiesterase 2A in the submandibular gland of
      mice.
AB  - OBJECTIVES: Phosphodiesterases comprise a superfamily of enzymes that hydrolyze
      and inactivate cyclic AMP (cAMP) and/or cyclic GMP (cGMP), thereby regulating
      cellular signaling mechanisms. We herein investigated the production of
      phosphodiesterase 2A (PDE2A) in the mouse submandibular gland. DESIGN: The
      expression and localization of the mRNA and protein of PDE2A were examined in the
      submandibular gland of male and female mice using the reverse transcription
      polymerase chain reaction, in situ hybridization, Western blotting, and
      immunohistochemistry. RESULTS: Among the different species of phosphodiesterases
      examined in the mouse submandibular gland, PDE2A, which hydrolyzes cAMP and cGMP,
      exhibited a marked sexual difference; it was more abundantly expressed in
      females. The mRNA and protein signals for PDE2A were intense in all acinar and
      duct portions, including the striated duct, in females, whereas in males, these
      signals were markedly weaker in the granular convoluted duct, the counterpart of
      the female striated duct, than in acini and other duct portions. Furthermore, the
      signals for protein kinases A and G1, which are intracellular effectors of cAMP
      and cGMP, respectively, were markedly weaker in the male granular convoluted
      duct. CONCLUSIONS: These results suggest that cyclic nucleotide-dependent
      signaling mechanisms function poorly in granular convoluted duct cells in the
      mouse submandibular gland.

PMID- 29597063
TI  - Implementing a Novel Guideline to Prevent Hospital-Acquired Pressure Ulcers in a
      Trauma Population: A Patient-Safety Approach.
AB  - BACKGROUND: The development of hospital-acquired pressure ulcers (HAPUs) is a
      common complication associated with immobilization and prolonged hospitalization
      in trauma patients. Our semi-annual Trauma Quality Improvement Program report
      identified HAPUs as an outlier complication. We used a hospital-wide initiative
      to reduce the incidence of HAPUs among our trauma patient population. Our study
      aimed to determine whether the implemented measures would decrease HAPUs
      incidence rates. STUDY DESIGN: We reviewed adult trauma patients during a 3-year
      period. The novel care-based platform and preventive measures for reducing HAPUs
      included the following components: pressure-reducing beds; improved and
      protocolized nutritional support; mandatory 2-hour change of posture; turning
      clocks; early surgical intervention; spot checks by our wound care nurse; and
      education to patients and caregivers. Paired-sample t-test and chi-square
      analyses were used, with significance defined as p < 0.05. RESULTS: A total of
      9,755 patients were admitted to our trauma services in the study period. Of
      these, HAPUs developed in 89 patients (mean age 57.9 years and 48 [54%] were
      female). The Injury Severity Score ranged from 1 to 75, with a mean of 20 in
      patients with HAPUs compared with 8 in patients without HAPUs during the same
      study period. The incidence of HAPUs at our institution was initially 1.36%,
      which decreased to 0.98% in year 2 and to 0.39% in year 3 (p = 0.002).
      CONCLUSIONS: The novel 7-step care-based process changes, acquisition of
      specialized equipment, and educational initiatives implemented were associated
      with a significant decrease in the incidence rates of HAPUs.

PMID- 29597064
TI  - Centromeric retrotransposons and centromere function.
AB  - The centromeric DNA of most multicellular eukaryotes consists of tandem repeats
      (TR) that bind centromere-specific proteins and act as a substrate for the
      efficient repair of frequent double-stranded DNA breaks. Some retrotransposons
      target active centromeres during integration with such specificity that they can
      be used to deduce current and historic centromere positions. The roles of
      transposons in centromere function remain incompletely understood but appear to
      include maintaining centromere size and increasing the repeat content of
      neocentromeres that lack TR. Retrotransposons are known to give rise to TR.
      Centromere-targeting elements thus have the potential to replace centromeric TR
      essentially in situ, providing a mechanism to explain the centromere paradox,
      that is, the presence of unrelated centromeric TRs in closely related species.

PMID- 29597065
TI  - Modeling cognitive deficits following neurodegenerative diseases and traumatic
      brain injuries with deep convolutional neural networks.
AB  - The accurate diagnosis and assessment of neurodegenerative disease and traumatic
      brain injuries (TBI) remain open challenges. Both cause cognitive and functional
      deficits due to focal axonal swellings (FAS), but it is difficult to deliver a
      prognosis due to our limited ability to assess damaged neurons at a cellular
      level in vivo. We simulate the effects of neurodegenerative disease and TBI using
      convolutional neural networks (CNNs) as our model of cognition. We utilize
      biophysically relevant statistical data on FAS to damage the connections in CNNs
      in a functionally relevant way. We incorporate energy constraints on the brain by
      pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that
      damage leads to human-like mistakes. Our experiments also provide quantitative
      assessments of how accuracy is affected by various types and levels of damage.
      The deficit resulting from a fixed amount of damage greatly depends on which
      connections are randomly injured, providing intuition for why it is difficult to
      predict impairments. There is a large degree of subjectivity when it comes to
      interpreting cognitive deficits from complex systems such as the human brain.
      However, we provide important insight and a quantitative framework for disorders
      in which FAS are implicated.

PMID- 29597066
TI  - The compensation effects of physiology and yield in cotton after drought stress.
AB  - The objective of this study was to investigate the root growth compensatory
      effects and cotton yield under drought stress. The results indicate that the root
      dry weight, boll weight, and cotton yield increased in both the drought-resistant
      cultivar (CCRI-45) and the drought-sensitive cultivar (CCRI-60). Compensation
      effects were exhibited under the three-day drought stress treatment at a soil
      relative water content (SRWC) of 60% and 45% during the seedling stage, and
      flowering and boll-forming stage over two years. The yield of the drought
      resistant cultivar (CCRI-45) was higher than the control, however, following the
      six-day 45% SRWC drought treatments, the yield of the drought-sensitive cultivar
      (CCRI-60) was lower than the control. The soluble sugar content, proline content,
      superoxide dismutase (SOD) activity, and peroxidase (POD) activity of the roots
      increased under drought stress and then decreased after re-watering, although the
      values remained higher than those of the controls for a short period. These
      physiological measures may represent stress reactions and thus may not indicate
      factors that result in compensation effects. However, catalase (CAT) activity and
      gibberellic acid (GA) content of the roots decreased under drought stress. After
      re-watering, the CAT activity and the GA content increased and were significantly
      higher than those of the controls under the six-day 60% SRWC and 45% SRWC drought
      treatments. The abscisic acid (ABA) content of the roots increased under drought
      stress. After re-watering, the ABA content decreased to a lower level under the
      three and six-day 60% SRWC and 45% SRWC drought treatments than in the controls.
      According to an analysis of various indicators, the interaction between ABA and
      GA signals may play an important role in root growth compensatory effects. In
      summary, the results demonstrate that moderate drought stress is beneficial to
      root growth and yield. This conclusion is of great significance to improving our
      understanding of the maximum utilization of limited water resources.

PMID- 29597067
TI  - Involvement of an autotoxic compound in asparagus decline.
AB  - Asparagus (Asparagus officinalis L.) is a widely cultivated perennial veritable
      and can be harvested more than ten years. However, the crop quality and yield
      decline after a few year's cultivation, which is called "asparagus decline". Even
      though those asparagus plants were replaced with new young asparagus plants, the
      productivity and quality of the crop remain relatively low, which is known as a
      "asparagus replant problem". One of the possible reasons for "asparagus decline"
      and "asparagus replant problem" is thought to be autotoxicity of asparagus.
      However, the compounds involved in the autotoxicity is not clear. The objective
      of this study was therefore to determine the potential role of autotoxicity in
      the "asparagus decline" and "asparagus replant problem". An aqueous methanol
      extract of 10-year-asparagus-cultivated soils inhibited the growth of asparagus
      seedlings and other two test plants with concentration dependent manner. The
      result confirmed that the asparagus soils have autotoxic activity. The extract
      was then purified by several chromatographies with monitoring the inhibitory
      activity and a potent growth inhibitory substance causing the autotoxic effect
      was isolated. The chemical structures of the compound was determined by spectral
      data to be trans-cinnamic acid. trans-Cinnamic acid inhibited the growth of
      asparagus seedlings at concentrations greater than 10 MUM. The concentrations
      required for 50% growth inhibition of asparagus (IC50) were 24.1-41.6 MUM. trans
      Cinnamic acid accumulated 174 MUM in the 10-year-asparagus-cultivated soils,
      which may be enough levels to cause the growth inhibition on asparagus
      considering its IC50 value. Therefore, trans-cinnamic acid may contribute to the
      autotoxic effect of asparagus soils, and may be in part responsible for
      "asparagus decline" and "asparagus replant problem".

PMID- 29597068
TI  - Proteomic analysis of tree peony (Paeonia ostii 'Feng Dan') seed germination
      affected by low temperature.
AB  - Seed germination is a critical process that is influenced by various factors. In
      the present study, the effect of low temperature (4  degrees C) on tree peony
      seed germination was investigated. Compared to seeds maintained at 25  degrees C,
      germination was inhibited when seeds were kept at 4  degrees C. Furthermore, low
      temperature exposure of seeds resulted in a delay in water uptake, starch
      degradation, and soluble sugar consumption and a subsequent increase in soluble
      protein levels. Two-dimensional gel electrophoresis (2-DE) proteomic analysis
      identified 100 protein spots. Comparative analysis indicated that low-temperature
      exposure apparently mainly affected glycolysis and the tricarboxylic acid (TCA)
      cycle, while also significantly affecting proteometabolism-related factors.
      Moreover, low-temperature exposure led to the induction of abscisic acid, whereas
      the gibberellin pathway was not affected. Further comparison of the two
      temperature conditions showed that low-temperature exposure delays carbohydrate
      metabolism, adenosine triphosphate (ATP) production, respiration, and proteolysis
      and increases defense response factors. To further examine the obtained proteomic
      findings, four genes were evaluated by quantitative polymerase chain reaction
      (qPCR). The obtained transcriptional results for the GAPC gene coincided with the
      translational results, thus further suggesting that the delay in glycolysis may
      play a key role in low-temperature-induced inhibition of seed germination.
      However, the other three genes examined, which included FPP synthase, PCNT115,
      and endochitinase, showed non-correlative transcriptional and translational
      profiles. Our results suggest that the exposure of tree peony seeds to low
      temperature results in a delay in the degradation of starch and other
      metabolites, which in turn affects glycolysis and some other processes, thereby
      ultimately inhibiting seed germination.

PMID- 29597069
TI  - A NIR sensor for cyanide detection and its application in cell imaging.
AB  - A novel 'D-pi-A' sensor 1 has been designed and prepared via the condensation
      reaction of 3-ethyl-2-methyl-1,3-benzothiazol-3-ium iodide and 5-nitro-o
      vanillin. Upon treatment with cyanide, sensor 1 exhibited a significant near
      infrared (NIR) fluorescence quenching at 663nm. The MS, IR, 1H NMR and DFT
      methods confirmed that the response of 1 to cyanide is due to the nucleophilic
      addition reaction, which results in the inhibition of the Intramolecular Charge
      Transfer (ICT) process in the sensor. Furthermore, sensor 1 was used for the
      determination of CN- in HeLa cells.

PMID- 29597070
TI  - Raman and FTIR spectroscopic studies on two hydroxylated tung oils (HTO) bearing
      conjugated double bonds.
AB  - Tung oil (TO) was used as a model compound to study two hydroxylated tung oils
      (HTO), prepared from TO by either aminolysis (HTO-am) or alcoholysis (HTO-al).
      Main bands in Raman and FTIR spectra were initially assigned based on the
      detailed analysis of the compound spectra before and after exposure to elevated
      temperature (200 degrees C). The effect of heat treatment in air on spectral
      bands, and especially on the changes associated with double bonds, were then
      investigated. In the present work, changes in spectral bands due to heat
      treatment were compared with those revealed in the previous work of others. The
      results show that the conjugated triene structure of TO has been retained during
      alcoholysis and aminolysis, to yield the HTOs studied; yet the change of the
      triene structure caused by heating is different among the three samples; the H
      bonding strength between OH and CO in HTO-am is higher than that in HTO-al; the
      changes in HTO vOH and vCO bands in FTIR caused by the present heat treatment
      were significant; for TO, there is a big difference between changes in spectra as
      caused by thermal exposure, compared to those caused by ageing under UV light or
      exposure to a catalyst. The present work has laid additional groundwork for
      further study of the reactions of such triply conjugated double bond structures
      under different ageing conditions.

PMID- 29597071
TI  - Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization
      enhancement and formulation for in vivo studies.
AB  - Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules
      facilitates the non-invasive real-time investigation of in vivo tissue metabolism
      in the time-frame of a few minutes; this opens up a new avenue in the development
      of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a
      hyperpolarization technique yielding a more than four orders of magnitude
      increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy
      studies. As reported in several studies, the dissolution Dynamic Nuclear
      Polarization polarization performance relies on the chemico-physical properties
      of the sample. In this study, we describe and quantify the effects of the
      different sample components on the dissolution Dynamic Nuclear Polarization
      performance of [1-13C]butyrate. In particular, we focus on the polarization
      enhancement provided by the incremental addition of the glassy agent dimethyl
      sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results
      obtained after injection in healthy rats are also reported, showing the
      feasibility of an in vivo Magnetic Resonance Spectroscopy study with
      hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

PMID- 29597072
TI  - Increased prevalence of anxiety disorders in third-generation migrants in
      comparison to natives and to first-generation migrants.
AB  - INTRODUCTION: We sought to examine the prevalence of anxiety disorders associated
      with migration in the first-, second- and third-generation. METHODS: The French
      Mental Health in the General Population cross-sectional survey interviewed 38,694
      individuals using the MINI. The prevalence of lifetime anxiety disorders, and
      comorbidities was compared between migrants and non-migrants and by generation.
      All analyses were adjusted for age, sex, and income and education levels.
      RESULTS: In comparison to natives, pooled anxiety disorders were more common
      among migrants (25.3% vs. 20.7%, OR = 1.24) and among the three studied
      generations of migrants. Moreover, the prevalence rate of the pooled anxiety
      disorders was significantly higher in third-generation migrants, in comparison to
      first-generation (26.7% vs. 22.6%, OR = 1.14). Prevalence rates were higher in
      migrants for panic disorder (6.6% vs. 5.3%, OR = 1.20), general anxiety disorder
      (15.0% vs. 12.0%, OR = 1.24), posttraumatic stress disorder (1.0% vs. 0.6%, OR =
      1.51), but not for social anxiety disorder. In comparison to natives, migrants
      with anxiety disorders had higher prevalence rates of suicide attempts (14.0% vs.
      12.8% for natives), psychotic disorders (8.3% vs. 5.7%), unipolar depressive
      disorder (29.5% vs. 25.4%), bipolar disorder (5.0% vs. 4.0%), and addictive
      disorders (9.6% vs. 6.2% for alcohol use disorder, 8.2% vs. 4.1% for substance
      use disorders). CONCLUSION: Migration was associated with a higher prevalence of
      all anxiety disorders, in the first, second and third generation, and associated
      with more psychiatric comorbidities. Moreover, the prevalence increased across
      generations, and was significantly higher among third-generation migrants, in
      comparison to first-generation.

PMID- 29597073
TI  - p21 Activated kinase 1: Nuclear activity and its role during DNA damage repair.
AB  - p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small
      GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified
      and/or overexpressed in several human cancer types including 25-30% of breast
      tumors. This enzyme plays a pivotal role in the control of a number of
      fundamental cellular processes by phosphorylating its downstream substrates. In
      addition to its role in the cytoplasm, it is well documented that PAK1 also plays
      crucial roles in the nucleus participating in mitotic events and gene expression
      through its association and/or phosphorylation of several transcription factors,
      transcriptional co-regulators and cell cycle-related proteins, including Aurora
      kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor
      (FKHR), estrogen receptor alpha (ERalpha), and Snail. More recently, PAK
      signaling has emerged as a component of the DNA damage response (DDR) as PAK1
      activity influences the cellular sensitivity to ionizing radiation and promotes
      the expression of several genes involved in the Fanconi Anemia/BRCA pathway. This
      review will focus on the nuclear functions of PAK1 and its role in the regulation
      of DNA damage repair.

PMID- 29597074
TI  - The variable lymphocyte receptor as an antibody alternative.
AB  - Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins in jawless
      vertebrates that function similarly to Ig antibodies. However, VLRs possess a
      distinct crescent-shaped structure and modularity that results in a concave
      binding interface that contrasts significantly with Ig antibodies. Antigen
      binding interactions result in specific, high affinity VLR binding interactions
      with both proteins and glycans. The natural sourcing of VLRs allows for
      immunization strategies, while the modularity enables a whole host of protein
      engineering approaches including consensus scaffolds, designed libraries and
      directed evolution with display technologies. VLR technologies have been recently
      deployed for applications in cell-specific targeting, drug delivery, tumor
      diagnostics and even protein stabilization. It is anticipated that the VLR field
      will continue to emerge to provide unique solutions for targeting glycans,
      evolutionarily conserved proteins and cellular specificity.

PMID- 29597076
TI  - Genome engineering for CNS injury and disease.
AB  - Recent developments in genome engineering methods have advanced our knowledge of
      central nervous system (CNS) function in both normal health and following disease
      or injury. This review discusses current literature using gene editing tools in
      CNS disease and injury research, such as improving viral-mediated targeting of
      cell populations, generating new methods for genome editing, reprogramming cells
      into CNS cell types, and using organoids as models of development and disease.
      Readers may gain inspiration for continuing research into new genome engineering
      methods and for therapies for CNS applications.

PMID- 29597075
TI  - Bionanotechnology for vaccine design.
AB  - There have been significant advances in the design of nanostructured scaffolds
      for eliciting robust immune responses. One method to produce strong immune
      responses is to emulate the appearance of a pathogen. Since pathogens such as
      viruses and bacteria often display multiple copies of ligands on their surfaces,
      the immune system is particularly sensitive towards multivalent displays of
      antigens. Consequently, when designing a vaccine, it is advantageous to decorate
      a nanostructured surface with multiple copies of an antigen. This review
      highlights the design and efficacy of a diverse set of recently developed
      nanostructured vaccine scaffolds.

PMID- 29597077
TI  - Urine Cotinine level with smoking history predicts a risk of coronary artery
      calcification.
AB  - We investigated whether urine cotinine level, alone or combined with smoking
      status and cumulative smoking amount, could predict coronary calcium (CAC) score
      increase over time. The study population included 10,980 subjects. We analysed an
      association between CAC score increase over time and single or combined smoking
      related factors. Urine cotinine level of >=100 ng/mL, current or ex-smokers, and
      cumulative smoking amount of >=1 pack-years (PY) showed significantly higher odds
      ratios (ORs) for CAC score increase over time. A combination of current smokers
      with >10 PY and urine cotinine level of >=100 ng/mL showed the highest OR.
      Irrespective of smoking status and cumulative smoking amount, all combinations
      with urine cotinine of >=100 ng/mL showed higher ORs than other combinations with
      urine cotinine level of <100 ng/mL. Urine cotinine levels can be useful to
      predict coronary artery calcification and encourage smokers to quit smoking.

PMID- 29597078
TI  - Toxicological effects of cadmium and lead on two freshwater diatoms.
AB  - In recent years, there have been significant advances in the knowledge and
      understanding of the pollution attributed to effects of aquatic toxic metals on
      fresh water benthic diatoms. In this study, the cell growth, chlorophyll a
      content and superoxide dismutase activity in Halamphora veneta (Kutzing) Levkov
      and Surirella crumena Brebisson exposed to cadmium and lead, were investigated.
      Furthermore, in order to explore the potential function of H. veneta on
      environmental monitoring and environmental remediation, expression of two genes
      (psbA, psaB) and morphological analysis of H. veneta were carried out. The cells
      growth of H. veneta and S. crumena were generally inhibited with cadmium and lead
      exposure during 96 h, while cells density of H. veneta was significantly
      increased under the low concentration at 24 h cadmium exposure. Our results
      indicated that H. veneta had a certain tolerance to toxic metals at initial
      treated time. In addition, the significantly changes of chlorophyll a content and
      SOD activities in H. veneta and S. crumena indicated that both photosynthetic
      system and the antioxidant system in benthic diatom might play important roles on
      the toxic metals tolerant mechanism. Meanwhile, it can be confirmed that the
      diatom photosynthetic systems play roles on toxic metals resistance inferred from
      the gene expression of psbA and psaB in H. veneta. Finally, the results of
      scanning electron microscopy showed that there was a slightly deformation on
      cells following the cadmium exposure in H. veneta, while obvious deformation with
      cell greatly widened after lead exposure. The present work will be helpful to
      understand the effect mechanisms of toxic metal by comparing two kinds of diatom
      on cell inhibition, biological response and morphological changes, which will
      provide more information for possible use of benthic diatoms in bioremediation.

PMID- 29597079
TI  - Assessment of Responsiveness to Everyday Non-Noxious Stimuli in Pain-Free
      Migraineurs With Versus Without Aura.
AB  - : Migraineurs with aura (MWA) express higher interictal response to non-noxious
      and noxious experimental sensory stimuli compared with migraineurs without aura
      (MWoA), but whether these differences also prevail in response to everyday non
      noxious stimuli is not yet explored. This is a cross-sectional study testing 53
      female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious
      psychophysical testing at a pain-free phase, and completed a Sensory
      Responsiveness Questionnaire and pain-related psychological questionnaires. The
      MWA group showed higher questionnaire-based sensory over-responsiveness (P =
      .030), higher magnitude of pain temporal summation (P = .031) as well as higher
      monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of
      migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its
      incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P =
      .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were
      positively correlated with attack frequency (r = .361, P = .008) and temporal
      summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA
      express higher everyday sensory responsiveness than MWoA, in line with higher
      response to experimental noxious stimuli. Abnormal scores of sensory
      responsiveness characterize people with sensory modulation dysfunction,
      suggesting possible underlying mechanisms overlap, and possibly high incidence of
      both clinical entities. PERSPECTIVE: This article presents findings
      distinguishing MWA, showing enhanced pain amplification, monthly attack
      frequency, and over-responsiveness to everyday sensations, compared with MWoA.
      Further, migraine is characterized by a high incidence of abnormal responsiveness
      to everyday sensation, specifically sensory over-responsiveness, that was also
      found related to pain.

PMID- 29597080
TI  - Individual Variation in Pain Sensitivity and Conditioned Pain Modulation in Acute
      Low Back Pain: Effect of Stimulus Type, Sleep, and Psychological and Lifestyle
      Factors.
AB  - : Generalized hyperalgesia and impaired pain modulation are reported in chronic
      low back pain (LBP). Few studies have tested whether these features are present
      in the acute phase. This study aimed to test for differences in pain presentation
      in early-acute LBP and evaluate the potential contribution of other factors to
      variation in sensitivity. Individuals within 2 weeks of onset of acute LBP (n =
      126) and pain-free controls (n = 74) completed questionnaires related to their
      pain, disability, behavior, and psychological status before undergoing
      conditioned pain modulation (CPM) and pain threshold (heat, cold, and pressure)
      testing at the back and forearm/thumb. LBP participants were more sensitive to
      heat and cold at both sites and pressure at the back than controls, without
      differences in CPM. Only those with high-pain (numeric rating scale >=4) were
      more sensitive to heat at the forearm and pressure at the back. Four subgroups
      with distinct features were identified: "high sensitivity," "low CPM efficacy,"
      "high sensitivity/low CPM efficacy," and "low sensitivity/high CPM efficacy."
      Various factors such as sleep and alcohol were associated with each pain measure.
      Results provide evidence for generalized hyperalgesia in many, but not all,
      individuals during acute LBP, with variation accounted for by several factors.
      Specific pain phenotypes provide candidate features to test in longitudinal
      studies of LBP outcome. PERSPECTIVE: Sensory changes indicative of
      increased/decreased central processing of pain and nociceptive input presented
      differently between individuals with acute LBP and were related to factors such
      as sleep and alcohol. This may underlie variation in outcome and suggest
      potential for early identification of individuals with poor long-term outcome.

PMID- 29597081
TI  - A Comparison of the Assay Sensitivity of Average and Worst Pain Intensity in
      Pharmacologic Trials: An ACTTION Systematic Review and Meta-Analysis.
AB  - : Identifying methods to improve assay sensitivity in randomized clinical trials
      (RCTs) may facilitate the discovery of efficacious pain treatments. RCTs
      evaluating pain treatments typically use average pain intensity (API) or worst
      pain intensity (WPI) as the primary efficacy outcome. However, little evidence is
      available comparing the assay sensitivity of these 2 measures. In this systematic
      review and meta-analysis, we comprehensively reviewed all low back pain,
      osteoarthritis pain, fibromyalgia, diabetic peripheral neuropathy pain, and
      postherpetic neuralgia RCTs that used a parallel group design. Eligibility
      required: 1) primary RCT report published between 1980 and 2016, 2) comparing 1
      or more active, efficacious pharmacologic pain treatment(s) with placebo, and 3)
      providing data on the standardized effect size (SES) for API as well as WPI for
      all treatment arms. Twenty-seven active versus placebo comparisons were
      identified in 23 eligible articles. Using a random-effects meta-analysis, API SES
      and WPI SES did not differ significantly (difference = -.021, 95% confidence
      interval = -.047 to .004, P = .12). The findings indicate that, depending on the
      objectives of the study, either API or WPI could be used as a primary outcome
      measure in clinical trials for the chronic pain conditions included in this
      analysis. PERSPECTIVE: Understanding the comparative assay sensitivity of API and
      WPI may advance pain treatment research. A meta-analysis of trials of efficacious
      pharmacologic treatments in 5 pain conditions did not show a statistically
      significant difference between the assay sensitivity of API and WPI.

PMID- 29597082
TI  - Prevalence and Pharmaceutical Treatment of Plantar Fasciitis in United States
      Adults.
AB  - : This study provides prevalence estimates of plantar fasciitis in U.S. adults,
      as well as the types and frequencies of pharmaceutical treatment specifically for
      this pain. Data are from the 2013 National Health and Wellness Survey, a large (n
      = 75,000) internet panel survey designed to approximate the adult U.S.
      POPULATION: Strengths of associations are determined using multivariable logistic
      regression. It was estimated that .85% (95% confidence interval [CI] = .77-.92)
      of the sample reported diagnosed plantar fasciitis with pain in the past month.
      Higher prevalence of plantar fasciitis was seen in women (1.19%; referent) versus
      men (.47%), in those aged 45 to 64 (1.33%) versus those aged 18 to 44 (.53%;
      referent) years, and in the obese (1.48%) versus those with a body mass <25
      (.29%; referent). Prescription medications for pain were used by 41.04% of
      plantar fasciitis respondents, but only 6.31% attributed this use specifically to
      plantar fasciitis pain. Nonsteroidal anti-inflammatory drugs (4.01%) and opioids
      (2.21%) were the most prevalent prescription drugs used specifically for plantar
      fasciitis pain. Almost 70% of individuals with plantar fasciitis used over the
      counter (OTC) analgesics for general pain management, with OTC nonsteroidal anti
      inflammatory drugs being used by 49.47% and acetaminophen by 26.93% of
      respondents. Individuals diagnosed by medical specialists had twice the odds of
      using prescription drugs as those diagnosed by other providers (odds ratio =
      2.12; 95% CI = 1.01-4.46). Non-Hispanic black individuals were more likely to use
      prescription pain medications specifically for plantar fasciitis pain than non
      Hispanic white individuals (odds ratio = 3.02; 95% CI = 1.05-8.70). PERSPECTIVE:
      The current study provides additional insights into the pain and disability
      associated with plantar fasciitis, as well as the pharmaceutical treatments being
      used for its management. Prescription as well as OTC medications are used to
      manage plantar fasciitis symptoms despite limited, if any, clinical trial data
      supporting their use.

PMID- 29597083
TI  - Traumatic Brain Injury and Receipt of Prescription Opioid Therapy for Chronic
      Pain in Iraq and Afghanistan Veterans: Do Clinical Practice Guidelines Matter?
AB  - : Clinical practice guidelines admonish against prescribing opioids for
      individuals with chronic pain and traumatic brain injury (TBI) because of
      increased risk for adverse outcomes, yet no studies have described opioid
      prescribing patterns in these higher-risk patients. Between October 2007 and
      March 2015, 53,124 Iraq and Afghanistan veterans with chronic pain not prescribed
      opioids in the previous year were followed for 1 year after completing a
      Comprehensive TBI Evaluation within the Department of Veterans Affairs health
      care facilities. Veterans reporting the most severe TBI sequelae (eg, loss of
      consciousness >30 minutes) were significantly more likely to receive short-term
      and long-term opioid therapy than those with less severe or no TBI sequelae (P
      values < .001). In analyses adjusted for sociodemographic characteristics,
      military service, pain disability, and previous nonopioid treatment modalities,
      veterans with moderate to severe TBI had a significantly increased risk of
      receiving opioid therapy. Veterans with moderate to severe TBI and comorbid post
      traumatic stress disorder and depression had an even greater risk of initiating
      long-term opioid therapy in the year after the Comprehensive TBI Evaluation
      (adjusted relative risk = 3.57 [95% confidence interval = 2.85-4.47]). Higher
      risk patients with chronic pain and TBI with mental health comorbidities may
      benefit from improved access to behavioral health and nonpharmacological
      therapies for chronic pain. PERSPECTIVE: Paradoxically, veterans with greater TBI
      severity and comorbid mental health burden are more likely to be prescribed
      opioids for chronic pain. More vulnerable veterans may benefit from improved
      access to behavioral health and nonpharmacological modalities for chronic pain,
      because of the health and safety risks of opioids.

PMID- 29597084
TI  - Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not
      Associated With Conditioned Pain Modulation.
AB  - : Healthy humans can be divided into the pain adaptive (PA) and the pain
      nonadaptive (PNA) groups; PA showed a greater decrease in pain rating to a cold
      pressor test (CPT) than PNA. This study examined if the dichotomy of pain
      adaptability existed in individuals with chronic musculoskeletal pain. CPTs at 2
      degrees C and 7 degrees C were used to assess the status of pain adaptability in
      participants with either chronic nonspecific low back pain or knee
      osteoarthritis. The participants' potency of conditioned pain modulation (CPM)
      and local inhibition were measured. The strengths of pain adaptability at both
      CPTs were highly correlated. PA and PNA did not differ in their demographic
      characteristics, pain thresholds from thermal and pressure stimuli, or potency of
      local inhibition or CPM. PA reached their maximum pain faster than PNA (t41 = 
      2.76, P < .01), and had a gradual reduction of pain unpleasantness over 7 days
      whereas PNA did not (F6,246 = 3.01, P = .01). The dichotomy of pain adaptability
      exists in musculoskeletal pain patients. Consistent with the healthy human study,
      the strength of pain adaptability and potency of CPM are not related. Pain
      adaptability could be another form of endogenous pain inhibition of which
      clinical implication is yet to be understood. PERSPECTIVE: The dichotomy of pain
      adaptability was identified in healthy humans. The current study confirms that
      this dichotomy also exists in individuals with chronic musculoskeletal pain, and
      could be reliably assessed with CPTs at 2 degrees C and 7 degrees C. Similar to
      the healthy human study, pain adaptability is not associated with CPM, and may
      reflect the temporal aspect of pain inhibition.

PMID- 29597085
TI  - Yttrium-doped iron oxide magnetic adsorbent for enhancement in arsenic removal
      and ease in separation after applications.
AB  - Arsenic contamination is one of serious environmental problems in the world. In
      this study, an innovative yttrium-doped iron oxide magnetic adsorbent was
      synthesized through a simple precipitation method for better arsenic
      decontamination and ease in separation after the application. The adsorbent with
      a rough surface and porous structure was aggregated of nano-sized irregular
      particles after heat-drying procedure. The point of zero charge value of the
      adsorbent was about 7.0, giving good performance on the arsenate removal at
      weakly acidic and neutral conditions. The thermal gravimetric analysis, X-ray
      powder diffraction and X-ray photoelectron spectroscopy studies demonstrated that
      hydroxyl groups from goethite and amorphous species of the adsorbent were mainly
      responsible for the arsenic adsorption. The adsorption equilibrium of arsenate
      and arsenite was respectively established in 24 and 4 h. The maximum adsorption
      capacities of As(V) and As(III) at pH 7.0 were 170.48 and 84.22 mg-As/g,
      respectively. The better fit by the Freundlich isotherm indicated the mechanism
      of multi-layer adsorption for the removal. Our study demonstrated that the
      material would be suitable for treating arsenic-containing water with higher
      efficiency and ease in use.

PMID- 29597087
TI  - Spatiotemporal evolution of the remotely sensed global continental PM2.5
      concentration from 2000-2014 based on Bayesian statistics.
AB  - PM2.5 pollution is threatening human health and quality of life, especially in
      some densely populated regions of Asia and Africa. This paper used remotely
      sensed annual mean PM2.5 concentrations to explore the spatiotemporal evolution
      of global continental PM2.5 pollution from 2000 to 2014. The work employed an
      improved Bayesian space-time hierarchy model combined with a multiscale
      homogeneous subdivision method. The statistical results quantitatively
      demonstrated a 'high-value increasing and low-value decreasing' trend. Areas with
      annual PM2.5 concentrations of more than 70MUg/m3 and less than 10MUg/m3
      expanded, while areas with of an annual PM2.5 concentrations of 10-25MUg/m3
      shrank. The most heavily PM2.5-polluted areas were located in northwest Africa,
      where the PM2.5 pollution level was 12.0 times higher than the average global
      continental level; parts of China represented the second most PM2.5-polluted
      areas, followed by northern India and Saudi Arabia and Iraq in the Middle East
      region. Nearly all (96.50%) of the highly PM2.5-polluted area (hot spots) had an
      increasing local trend, while 68.98% of the lightly PM2.5-polluted areas (cold
      spots) had a decreasing local trend. In contrast, 22.82% of the cold spot areas
      exhibited an increasing local trend. Moreover, the spatiotemporal variation in
      the health risk from exposure to PM2.5 over the global continents was also
      investigated. Four areas, India, eastern and southern China, western Africa and
      central Europe, had high health risks from PM2.5 exposure. Northern India,
      northeastern Pakistan, and mid-eastern China had not only the highest risk but
      also a significant increasing trend; the areas of high PM2.5 pollution risk are
      thus expanding, and the number of affected people is increasing. Northern and
      central Africa, the Arabian Peninsula, the Middle East, western Russia and
      central Europe also exhibited increasing PM2.5 pollution health risks.

PMID- 29597086
TI  - The use of longitudinal cohorts for studies of dengue viral pathogenesis and
      protection.
AB  - In this review, we describe how longitudinal prospective community-based, school
      based, and household-based cohort studies contribute to improving our knowledge
      of viral disease, focusing specifically on contributions to understanding and
      preventing dengue. We describe how longitudinal cohorts enable measurement of
      essential disease parameters and risk factors; provide insights into biological
      correlates of protection and disease risk; enable rapid application of novel
      biological and statistical technologies; lead to development of new interventions
      and inform vaccine trial design; serve as sentinels in outbreak conditions and
      facilitate development of critical diagnostic assays; enable holistic studies on
      disease in the context of other infections, comorbidities, and environmental risk
      factors; and build research capacity that strengthens national and global public
      health response and disease surveillance.

PMID- 29597088
TI  - LDR reverses DDP resistance in ovarian cancer cells by affecting ERCC-1, Bcl-2,
      Survivin and Caspase-3 expressions.
AB  - BACKGROUND: Ovarian cancer is the most frequent cause of death resulting from
      malignant gynecological tumors. After surgical intervention, cisplatin (DDP) is a
      major chemotherapy drug for ovarian cancer, but the ovarian cancer cells tend to
      develop DDP resistance in the clinical setting. Tumor cells are sensitive to low
      dose radiation (LDR). However, how the LDR therapy improves the effects of
      chemotherapy drugs on ovarian cancer is not well understood. This study aimed to
      explore this issue. METHODS: The SKOV3/DDP cells were divided into 3 groups,
      including low-dose group, conventional-dose group, and control group (no
      radiation). Cell counting kit-8 assay was performed to measure cell
      proliferation. Flow cytometric analysis was then utilized to quantify the
      apoptosis with classical Annexin V/propidium iodide co-staining. And Real-time
      quantitative PCR and western blot were eventually used to analyze the mRNA and
      protein levels of excision repair cross complementing-group 1 (ERCC1), B-cell
      lymphoma 2 (Bcl-2), Survivin and Caspase-3, respectively. RESULTS: The IC50 value
      of DDP in the low-dose group was significantly lower compared with the other two
      groups. Compared with the conventional-dose group and control group, LDR
      treatment resulted in significantly more apoptosis. Besides, LDR treatment
      significantly decreased the mRNA and protein expression of ERCC1, Bcl-2, and
      Survivin, and enhanced the mRNA and protein expression of Caspase-3 compared with
      the other two groups. CONCLUSIONS: LDR reversed DDP resistance in SKOV3/DDP cells
      possibly by suppressing ERCC1, Bcl-2, and Survivin expressions, and increasing
      Caspase-3 expression.

PMID- 29597089
TI  - Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for
      effective treatment of pancreatic cancer.
AB  - Pancreatic cancer is considered as one of the most lethal type of cancer with a
      poor 5-year survival rate. Cancer metastasis represents one of the primary cause
      which limits therapy against this disease. Current chemotherapeutic approaches
      are largely ineffective, thus calling for the development of alternative
      strategies to combat this disease. In this regard, numerous studies have reported
      the anticancer effect of curcumin in different types of cancer including
      pancreatic cancer. However, low aqueous solubility, poor stability and decreased
      bioavailability associated with native curcumin holds back its use in clinical
      settings. In order to enhance its therapeutic value, polymeric nanoparticles
      (NPs) represent an ideal delivery system. Further, surface modification of NPs
      with various macromolecules, such as chitosan and polyethylene glycol (PEG) holds
      tremendous potential for improving the bioavailability and circulation time of
      native drug in the blood. In the present study, we have explored the above
      approach to formulate curcumin-loaded Poly d,l-lactide-co-glycolide (PLGA) NPs
      and further surface coated it with chitosan and PEG (CNPs) with anticipation to
      reduce the limitations associated with native curcumin delivery for achieving an
      optimum therapeutic effect. Results revealed that NPs are of nanometre range
      having smooth and spherical surface morphology and with an efficient loading of
      curcumin. In vitro, cellular studies revealed superior cytotoxicity, enhanced
      anti-migratory, anti-invasive and apoptosis-inducing ability of CNPs in
      metastatic pancreatic cancer in comparison to a native counterpart. Thus, we
      anticipate that the results from these studies can open up novel options for the
      treatment of pancreatic cancer.

PMID- 29597090
TI  - Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer
      stemness and inhibits proliferation through PI3K/AKT pathway in esophageal
      squamous cell carcinoma.
AB  - Radiotherapy is one of the common treatments for esophageal squamous cell
      carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not
      solved. Lobaplatin (LBP) is known to have powerful clinical anti-tumor activities
      in various tumors, but its effect in radiotherapy is rarely studied. Here we
      report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells
      with LBP and radiation, both separately and in combination. Untreated cells were
      set as control groups. We found that LBP inhibited ESCC cell growth and enhanced
      their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined
      with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP
      obviously decreased the expression of cancer stem cells biomarker CD271 both in
      vitro and in vivo. The molecular mechanism was related to the downregulation of
      Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings
      indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing
      radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT
      pathway. These results provide a foundation for the combined therapy of radiation
      and LBP for ESCC in clinical practice.

PMID- 29597091
TI  - A review on phytochemistry and therapeutic uses of Hibiscus sabdariffa L.
AB  - Hibiscus sabdariffa L. (roselle) belonging to the Malvaceae family is widely
      grown in many countries. This plant is often used in the traditional medicine
      being rich in phytochemicals like polyphenols especially anthocyanins,
      polysaccharides and organic acids thus having enormous prospective in modern
      therapeutic uses. The study aimed to review and document all the available
      evidence and information about the calyces of Hibiscus sabdariffa (roselle) with
      the special focus on their nutritional composition, bioactive constituents and
      therapeutic uses. The electronic database was searched up to 2017, using keywords
      Hibiscus sabdariffa, chemical constituents of roselle, therapeutic uses of
      roselle. Journals, books and conference proceedings were also searched. The
      review provides valuable information about the nutraceutical component of
      Hibiscus sabdariffa L. and their utilization for curing various degenerative
      diseases like hypertension, hyperlipidemia, cancer and other inflammatory
      diseases of liver and kidney. Their toxicological effects have also been
      discussed from a safety point of view. Most studies supported and provided the
      scientific basis for the statement that Hibiscus sabdariffa and their active
      constituents play an important role in the prevention of chronic and degenerative
      diseases that are associated with oxidative stress. Our study suggests, that good
      research is needed, to establish a potential strategy that can balance the
      pharmacological and toxic effects of roselle and standardized fingerprint of
      Hibiscus sabdariffa is required internationally for quality control.

PMID- 29597092
TI  - Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness
      through inhibition of YAP activation and increases susceptibility to
      chemotherapeutic agents.
AB  - This study aims to explore the roles and related mechanisms of HuR in
      osteosarcoma (OS) cells migration, invasion, stemness and chemotherapeutical
      sensitivity. Here, we found that HuR exhibited higher level in OS tissues
      compared with the adjacent normal tissues. Knockdown of HuR with lentivirus
      infection suppressed OS cells migration and invasion, and thus the epithelial
      mesenchymal transition (EMT) process. Additionally, HuR knockdown inhibited OS
      cells stemness. Mechanistically, YAP was identified as a direct target of HuR in
      OS cells, and HuR knockdown decreased its expression. Moreover, YAP
      transcriptional activity was attenuated by HuR knockdown, and RNA immunization co
      precipitation (RIP) assay showed that HuR directly bound with YAP. Importantly,
      YAP overexpression rescued the inhibition of HuR knockdown on OS cells migration,
      invasion and stemness. Furthermore, HuR knockdown enhanced adriamycin sensitivity
      in OS cells, this effect was attenuated by YAP overexpression too. Importantly,
      HuR and YAP expression was positively correlated in OS tissues. Therefore, HuR
      acts as a tumor promoter by enhancing YAP expression in OS cells.

PMID- 29597093
TI  - Arginine: Challenges and opportunities of this two-faced molecule in cancer
      therapy.
AB  - Numerous antitumor therapies have been developed based on the differences in
      cells' metabolisms. Regarding the important role of arginine (Arg) in the
      regulation of multiple metabolic and signaling pathways, its deprivation has been
      proposed as a good strategy for tumor regression in tumors with defected Arg
      metabolic enzymes like argininosuccinate synthase 1 (ASS1). However, modulatory
      effect of Arg on various cancers is also a controversial issue. Therefore, this
      review article intends to address some of the challenges faced by Arg deprivation
      method as well as Arg administration for cancer therapy.

PMID- 29597095
TI  - Speech and language delay in a patient with WDR4 mutations.
AB  - Primordial dwarfism (PD) is mainly characterized by growth deficiency with
      heterogeneous phenotypes. A group of genes are known to be associated with PD or
      PD-related syndrome. WD repeat domain 4 (WDR4) is recently reported to be
      responsible for PD. Here we report a 6-year-old boy from a non-consanguineous
      couple with motor and speech delay as well as intellectual disability. Whole
      exome sequencing (WES) identified a missense mutation (NM_033661.4:c.491A > C;
      p.(Asp164Ala)) and a small insertion (NM_033661.4:c.940dupC; p.(Leu314Profs*16))
      of WDR4 in this patient. Two novel mutations confirmed by Sanger sequencing are
      from father and mother respectively according to a recessive inheritance pattern.
      Asp164Ala located in functional region is predicted to be deleterious by two
      kinds of algorithm. The small insertion causing a frameshift mutation leads to
      truncated protein. In this study, we present two novel WDR4 mutations responsible
      for PD in a 6-year-old patient, expanding the molecular and phenotype spectrum of
      WDR4-related PD.

PMID- 29597094
TI  - Membrane properties that shape the evolution of membrane enzymes.
AB  - Spectacular recent progress in structural biology has led to determination of the
      structures of many integral membrane enzymes that catalyze reactions in which at
      least one substrate also is membrane bound. A pattern of results seems to be
      emerging in which the active site chemistry of these enzymes is usually found to
      be analogous to what is observed for water soluble enzymes catalyzing the same
      reaction types. However, in light of the chemical, structural, and physical
      complexity of cellular membranes plus the presence of transmembrane gradients and
      potentials, these enzymes may be subject to membrane-specific regulatory
      mechanisms that are only now beginning to be uncovered. We review the membrane
      specific environmental traits that shape the evolution of membrane-embedded
      biocatalysts.

PMID- 29597096
TI  - A sustainable solution for the activities of the European network for
      surveillance of congenital anomalies: EUROCAT as part of the EU Platform on Rare
      Diseases Registration.
AB  - The European Commission through its Directorates-General Joint Research Centre
      (DG JRC) and Health and Food Safety (DG SANTE) is developing the European
      Platform on Rare Diseases Registration (EU RD Platform) with the objective to set
      European-level standards for data collection and data sharing. In the field of
      rare diseases the EU RD Platform will be a source of information on available
      rare disease patient data with large transnational European coverage. One main
      function of the EU RD Platform is to enable interoperability for the >600
      existing RD registries in Europe. The second function is to offer a sustainable
      solution for two large European surveillance networks: European Surveillance of
      Congenital Anomalies (EUROCAT) and Surveillance of Cerebral Palsy in Europe
      (SCPE). EUROCAT is European network of population-based registries for the
      epidemiological surveillance of congenital anomalies. It covers about one third
      of the European birth population. The Central Database contains about 800,000
      cases with congenital anomalies among livebirths, stillbirths and terminations of
      pregnancy, reported using the same standardised classification and coding. These
      high quality data enables epidemiological surveillance of congenital anomalies,
      which includes estimating prevalence, prenatal diagnosis and perinatal mortality
      rates and the detection of teratogenic exposures among others. The network also
      develops recommendations for primary prevention in the Rare Diseases National
      Plans for medicinal drugs, food/nutrition, lifestyle, health services, and
      environmental pollution. The network has received the European Commission's
      support since its inception. In order to offer a sustainable solution for the
      continuation of EUROCAT activities, it was agreed that EUROCAT would become part
      of the EU RD Platform. In 2015, the European level-coordination activities and
      the Central Database were transferred to the DG JRC, where the JRC-EUROCAT
      Central Registry is now located. This paper describes the functioning of EUROCAT
      in the new setting, and gives an overview of the activities and the organisation
      of the JRC-EUROCAT Central Registry.

PMID- 29597097
TI  - Performance evaluation of four type-specific commercial assays for detection of
      herpes simplex virus type 1 antibodies in a Middle East and North Africa
      population.
AB  - BACKGROUND: The number of diagnostic assays for the detection of herpes simplex
      virus type 1 (HSV-1) antibodies has increased over the years. However, their
      performance characteristics could vary among global populations. OBJECTIVE: To
      investigate performance of two commercial ELISA kits, HerpeSelect(r) 1 ELISA and
      Euroimmun Anti-HSV-1 (gC1) ELISA (IgG); and two commercial immunoblot
      (IB)/Western blot (WB) assays, HerpeSelect(r) 1 and 2 Immunoblot IgG, and
      Euroimmun Anti-HSV-1/HSV-2 gG2 Euroline-WB (IgG/IgM); in detecting HSV-1
      antibodies in a Middle East and North Africa (MENA) population. STUDY DESIGN:
      Blood specimens were collected from blood donors in Doha, Qatar, June 2013-2016.
      Twenty specimens were randomly selected from 10 MENA nationalities (Egypt, Iran,
      Jordan, Lebanon, Pakistan, Palestine, Qatar, Sudan, Syria, and Yemen; total =
      200), and tested for HSV-1 antibodies. RESULTS: Across all six comparisons
      between assays, positive percent agreement ranged between 95.7% (95% CI: 91.4
      98.3%) and 100.0% (95% CI: 97.8-100.0%). Negative percent agreement ranged
      between 86.2% (95% CI: 68.3-96.1%) and 96.2% (95% CI: 80.4-99.9%). Overall
      percent agreement ranged between 95.7% (95% CI: 91.7-97.8%) and 99.4% (95% CI:
      96.7-99.9%). Cohen's kappa statistic ranged between 0.84 (95% CI: 0.73-0.95) and
      0.98 (95% CI: 0.93-1.00). Compared against IB/WB, HerpeSelect(r) and Euroimmun
      had sensitivities and specificities >96% and >86%, respectively. Positive and
      negative predictive values were >97% and >83%, respectively. CONCLUSION: The
      assays showed excellent concordance with one another, and with a high kappa
      statistic. The ELISA kits demonstrated robust diagnostic performance compared to
      the IB/WB assays. These findings support the assays' utility in clinical
      diagnosis and research in MENA populations.

PMID- 29597098
TI  - Long-term survival after pulmonary resections for multiple metastases from
      gastric cancer: A case report.
AB  - INTRODUCTION: The prognosis of pulmonary resection for metastatic gastric cancer
      is poor even though solitary metastasis. Long-term survival after pulmonary
      resections for multiple pulmonary metastases from gastric cancer is extremely
      rare. CASE PRESENTATION: The patient was 67-year old man who underwent a distal
      gastrectomy for early gastric cancer. Wedge resections of the right upper and
      lower lobes and right lower lobectomy were performed for metastases from gastric
      cancer at 29 months and 55 months after the gastrectomy, respectively. As of 96
      months after the first pulmonary metastasectomy, this patient continues to be
      recurrence-free. DISCUSSION: Multiple pulmonary metastases after gastrectomy are
      not considered candidates for surgery. Although systemic chemotherapy is the
      standard therapy for metastatic gastric cancer, the prognosis is extremely poor.
      In this case with favorable prognostic factors, such as long disease-free
      intervals or absence of extrapulmonary metastasis, pulmonary metastasectomy could
      be a therapeutic option in patients despite the presence of multiple pulmonary
      metastases. CONCLUSIONS: Our case suggests that even in cases involving multiple
      pulmonary metastases, pulmonary metastasectomy might be an effective therapeutic
      option that can improve survival.

PMID- 29597099
TI  - Electrochemically mediated polymerization for highly sensitive detection of
      protein kinase activity.
AB  - Protein kinases play a pivotal role in cellular regulation and signal
      transduction, the detection of protein kinase activity and inhibition is
      therefore of great importance to clinical diagnosis and drug discovery. In this
      work, a novel electrochemical platform using the electrochemically mediated
      polymerization as an efficient and cost-effective signal amplification strategy
      is described for the highly sensitive detection of protein kinase activity. This
      platform involves 1) the phosphorylation of substrate peptide by protein kinase,
      2) the attachment of alkyl halide to the phosphorylated sites via the carboxylate
      Zr4+-phosphate chemistry, and 3) the in situ grafting of electroactive polymers
      from the phosphorylated sites through the electrochemically mediated atom
      transfer radical polymerization (eATRP) at a negative potential, in the presence
      of the surface-attached alkyl halide as the initiator and the electroactive tag
      conjugated acrylate as the monomer, respectively. Due to the electrochemically
      mediated polymerization, a large number of electroactive tags can be linked to
      each phosphorylated site, thereby greatly improving the detection sensitivity.
      This platform has been successfully applied to detect the activity of cAMP
      dependent protein kinase (PKA) with a detection limit down to 1.63 mU mL-1.
      Results also demonstrate that it is highly selective and can be used for the
      screening of protein kinase inhibitors. The potential application of our platform
      for protein kinase activity detection in complex biological samples has been
      further verified using normal human serum and HepG2 cell lysate. Moreover, our
      platform is operationally simple, highly efficient and cost-effective, thus
      holding great potential in protein kinase detection and inhibitor screening.

PMID- 29597100
TI  - Cellulosome assembly: paradigms are meant to be broken!
AB  - Cohesin-Dockerin interactions are at the core of cellulosomal assembly and
      organization. They are highly specific and form stable complexes, allowing
      cellulosomes to adopt distinct conformations. Each cellulosomal system seems to
      have a particular organizational strategy that can vary in complexity according
      to the nature of its Cohesin-Dockerin interactions. Hence, several efforts have
      been undertaken to reveal the mechanisms that govern the specificity, affinity
      and flexibility of these protein-protein interactions. Here we review the most
      recent studies that have focused on the structural aspects of Cohesin-Dockerin
      recognition. They reveal an ever-increasing number of subtle intricacies
      suggesting that cellulosome assembly is more complex than was initially thought.

PMID- 29597102
TI  - Communication, compassion, and computers: Adolescents' and adults' evaluations of
      online and face-to-face deception.
AB  - We explored Canadian adolescents', emergent adults', and adults' understandings
      of deception in computer mediated communication (CMC) compared to face to face
      (FtF). Participants between 13 and 50 years read vignettes of different types of
      questionable behaviour that occurred online or in real life, and were asked to
      judge whether deception was involved, and the acceptability of the behaviour. Age
      groups evaluated deception similarly; however, adolescents held slightly
      different views from adults about what constitutes deception, suggesting that the
      understanding of deception continues to develop into adulthood. Furthermore, CMC
      behaviour was rated as more deceptive than FtF in general, and participants
      scoring higher on compassion perceived vignettes to be more deceptive. This study
      is a step towards better understanding the relationships between perceptions of
      deception across adolescence into adulthood, mode of communication, and
      compassion, and may have implications for how adults communicate with youth about
      deception in CMC and FtF contexts.

PMID- 29597101
TI  - Mother-to-child transmission of hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is a worldwide health problem. Based on results
      of a serosurvey, global prevalence is estimated to be 2,5%, and women account for
      about 35.8% of the cases. For pregnant women the prevalence is lower and showed a
      range between 0.24% to 4.3%. Sinse mechanisms and timing of mother to child
      transmission are not fully understood, efforts are made to assess and understand
      its risk factors. The purpose of this review was to synthesize the evidence about
      the mother-to-child transmission of hepatitis C virus and review its risk
      factors.

PMID- 29597103
TI  - The role of observed autonomy support, reciprocity, and need satisfaction in
      adolescent disclosure about friends.
AB  - Although research increasingly addresses the role of parenting in fostering
      adolescent disclosure, most research relied on self-report measures of parenting
      and did not address the role of autonomy support. In the present observational
      study (conducted in Belgium), with 62 mother-adolescent dyads (mean age mothers =
      44 years; mean age adolescents = 14 years; 77% of adolescents female), we rated
      mothers' provision of autonomy support during a 10-minute conversation about
      friendships. We found that observed maternal autonomy support was related
      positively to adolescents' degree of and volitional reasons for disclosure about
      friends. These associations were mediated by observed non-verbal reciprocity
      during the conversation and by adolescent satisfaction of their needs for
      autonomy and relatedness. Mothers' autonomy-support and mother-adolescent
      reciprocity also predicted mothers' own psychological need satisfaction and
      conversation pleasure. The relevance of the findings for adolescent autonomy and
      disclosure are discussed.

PMID- 29597104
TI  - Development of a coping intervention to improve traumatic stress and HIV care
      engagement among South African women with sexual trauma histories.
AB  - This paper describes the development and preliminary trial run of ImpACT
      (Improving AIDS Care after Trauma), a brief coping intervention to address
      traumatic stress and HIV care engagement among South African women with sexual
      trauma histories. We engaged in an iterative process to culturally adapt a
      cognitive-behavioral intervention for delivery within a South African primary
      care clinic. This process involved three phases: (a) preliminary intervention
      development, drawing on content from a prior evidence-based intervention; (b)
      contextual adaptation of the curriculum through formative data collection using a
      multi-method qualitative approach; and (c) pre-testing of trauma screening
      procedures and a subsequent trial run of the intervention. Feedback from key
      informant interviews and patient in-depth interviews guided the refinement of
      session content and adaptation of key intervention elements, including culturally
      relevant visuals, metaphors, and interactive exercises. The trial run curriculum
      consisted of four individual sessions and two group sessions. Strong session
      attendance during the trial run supported the feasibility of ImpACT. Participants
      responded positively to the logistics of the intervention delivery and the
      majority of session content. Trial run feedback helped to further refine
      intervention content and delivery towards a pilot randomized clinical trial to
      assess the feasibility and potential efficacy of this intervention.

PMID- 29597105
TI  - Experimental and simulation research on the screening effect of the pixelated CZT
      imaging detector.
AB  - Massive efforts have been made to investigate the characteristics of the CdZnTe
      detector under different extreme conditions. In this paper, we experimented with
      different radiation sources to investigate the imaging screening effect of the
      pixelated CdZnTe detector under ultrahigh irradiance. A donut-shaped irradiation
      image was obtained due to the increase in the X-ray tube current or the tube
      voltage. Moreover, statistical data revealed that the total count of all pixels
      was not significantly different, while the event-count of irradiated area pixels
      decreased significantly. A consequence of the screening effect was that the event
      counts redistributed among pixels that are located in the irradiated area, while
      the inner electric field was distorted. This leads to the catastrophic
      performance degradation of the central pixels. According to the Poisson equation,
      we developed a theoretical model of the CdZnTe detector using the finite element
      software COMSOL to enable an in-depth investigation of carrier collection in the
      CdZnTe crystal. A comparison between the simulations and the test results showed
      that pixels in the central irradiated area are completely screened under the
      ultrahigh irradiance because of the emergence of the relatively higher potential
      region, which can distort the electron drift path. Furthermore, the photon
      generated signal can be collected only partly at the edge of the irradiated area,
      which was relatively stable because the collection area in the CdZnTe volume was
      relatively limited. The imaging results deduced from the simulations are well
      consistent with the experimental data.

PMID- 29597106
TI  - Biological nitrogen removal using soil columns for the reuse of reclaimed water:
      Performance and microbial community analysis.
AB  - The main aim of this study was to remove nitrogen compounds from reclaimed water
      and reuse the water in semi-arid riverine lake systems. In order to assess the
      nitrogen removal efficiencies in different natural environments, laboratory scale
      column experiments were performed using sterilized soil (SS), silty clay (SC),
      soil with submerged plant (SSP) and biochar amendment soil (BCS). The initial
      concentration of NO3--N and the flow rate was maintained constant at 15 mg L-1
      and 0.6 +/- 0.1 m d-1, respectively. Among the tested columns, both SSP and BCS
      were able to achieve NO3--N levels <0.2 mg L-1 in the treated reclaimed water.
      The results from bacterial community structure analysis, using 454 pyrosequencing
      of 16s rRNA genes, showed that the dominant denitrifier was Bacillus at the
      genera level.

PMID- 29597107
TI  - The effect of bacterial and archaeal populations on anaerobic process fed with
      mozzarella cheese whey and buttermilk.
AB  - Dairy wastes can be conveniently processed and valorized in a biorefinery value
      chain since they are abundant, zero-cost and all year round available. For a
      comprehensive knowledge of the microbial species involved in producing biofuels
      and valuable intermediates from dairy wastes, the changes in bacterial and
      archaeal population were evaluated when H2, CH4 and chemical intermediates were
      produced. Batch anaerobic tests were conducted with a mixture of mozzarella
      cheese whey and buttermilk as organic substrate, inoculated with 1% and 3% w/v
      industrial animal manure pellets. The archaeal methanogens concentration
      increased in the test inoculated at 3% (w/v) when H2 and CH4 production occurred,
      being 1 log higher than that achieved in the test inoculated at 1% (w/v). Many
      archaeal species, mostly involved in the production of CH4, were identified by
      sequencing denaturing gradient gel electrophoresis (DGGE) bands. Methanoculleus,
      Methanocorpusculum and Methanobrevibacter genera were dominant archaea involved
      in the anaerobic process for bioenergy production from mozzarella cheese whey and
      buttermilk mixture.

PMID- 29597108
TI  - Biological approaches to tackle heavy metal pollution: A survey of literature.
AB  - Pollution by heavy metals has been identified as a global threat since the
      inception of industrial revolution. Heavy metal contamination induces serious
      health and environmental hazards due to its toxic nature. Remediation of heavy
      metals by conventional methods is uneconomical and generates a large quantity of
      secondary wastes. On the other hand, biological agents such as plants,
      microorganisms etc. offer easy and eco-friendly ways for metal removal; hence,
      considered as efficient and alternative tools for metal removal. Bioremediation
      involves adsorption, reduction or removal of contaminants from the environment
      through biological resources (both microorganisms and plants). The heavy metal
      remediation properties of microorganisms stem from their self defense mechanisms
      such as enzyme secretion, cellular morphological changes etc. These defence
      mechanisms comprise the active involvement of microbial enzymes such as
      oxidoreductases, oxygenases etc, which influence the rates of bioremediation.
      Further, immobilization techniques are improving the practice at industrial
      scales. This article summarizes the various strategies inherent in the biological
      sorption and remediation of heavy metals.

PMID- 29597109
TI  - Dispersive liquid-liquid microextraction for the quantification of venlafaxine in
      environmental waters.
AB  - The present work describes a new methodology for the detection of the
      antidepressant venlafaxine (VEN) in aquatic environments using dispersive liquid
      liquid microextraction followed by high performance liquid chromatography with
      fluorescence detection (DLLME-HPLC-FLD). The method developed is fast, low cost,
      easy to apply, uses a small volume of organic solvents and allows the
      simultaneous extraction of various samples. The DLLME-HPLC-FLD method presented a
      linearity range from 25 to 1500 ng L-1, a detection limit of 24.2 +/- 0.2 ng L-1,
      and an enrichment factor of 75 +/- 4. Recovery tests using solutions of NaCl and
      humic acids showed that ionic strength and organic matter do not influence the
      efficiency of the extraction, with extraction recoveries above 77%. Finally, the
      optimized method was applied to the analysis of water samples from different
      origins and VEN was only detected in one water sample obtained from a waste water
      treatment plant (WWTP), which had a concentration of 175 +/- 5 ng L-1. Recovery
      tests performed in environmental aquatic samples demonstrated that the developed
      extraction procedure is not influenced by the complex water matrices, with
      results ranging from 76 to 93%.

PMID- 29597110
TI  - A comparative study of longitudinal dispersion models in rigid vegetated compound
      meandering channels.
AB  - Releasing and mixing of pollutants in rivers can cause serious threats for
      downstream users. Longitudinal dispersion is an important factor in describing
      pollutant transport process in rivers. The focus of this study is on the effect
      of floodplain rigid vegetation characteristics including its arrangement, density
      and relative depth (the ratio of the flow depth in the main channel to that over
      floodplain) on flow and longitudinal dispersion coefficient in a meandering
      channel with compound cross section. Digital image processing technique was used
      to measure the tracer concentration. Sequential images were continuously captured
      at seven sections downstream of release point. PVC cylinders were installed over
      the floodplain to simulate rigid vegetation in tandem and random arrangements.
      Acoustic Doppler Velocimeter (Micro-ADV) was used to measure 3-D velocity
      components. The results showed that roughening the flood plain with stems
      increases the longitudinal flow velocity and Reynolds shear stress in the main
      channel, while these parameters decrease in the flood plain compared to non
      vegetated cases. As a result, in the presence of rigid vegetation, the travel
      time decreases in the main channel up to 20% compared to non-vegetated
      conditions. As the relative flow depth increases, the dimensionless longitudinal
      dispersion coefficient, K/U*H, decreases up to 74%. Also, the dimensionless
      longitudinal dispersion coefficient increases up to 38% with stem density in a
      specific relative flow depth of Dr = 0.11. Finally, a comparison has been made
      between laboratory data and some well-known previously reported models. Later,
      the most accurate equations are presented for predicting the longitudinal
      dispersion coefficient in rigid vegetated compound meandering channels. The
      results of the present study reveal that rigid vegetation over flood plain can be
      used as an alternative method in river rehabilitation projects for environmental
      management purposes.

PMID- 29597111
TI  - Improving fire season definition by optimized temporal modelling of daily human
      caused ignitions.
AB  - Wildfire suppression management is usually based on fast control of all
      ignitions, especially in highly populated countries with pervasive values-at
      risk. To minimize values-at-risk loss by improving response time of suppression
      resources it is necessary to anticipate ignitions, which are mainly caused by
      people. Previous studies have found that human-ignition patterns change spatially
      and temporally depending on socio-economic activities, hence, the deployment of
      suppression resources along the year should consider these patterns. However,
      full suppression capacity is operational only within legally established fire
      seasons, driven by past events and budgets, which limits response capacity and
      increases damages out of them. The aim of this study was to assess the temporal
      definition of fire seasons from the perspective of human-ignition patterns for
      the case study of Spain, where people cause over 95% of fires. Humans engage in
      activities that use fire as a tool in certain periods within a year, and in
      locations linked to specific spatial factors. Geographic variables (population,
      infrastructures, physiography and land uses) were used as explanatory variables
      for human-ignition patterns. The changing influence of these geographic variables
      on occurrence along the year was analysed with day-by-day logistic regression
      models. Daily models were built for all the municipal units in the two climatic
      regions in Spain (Atlantic and Mediterranean Spain) from 2002 to 2014, and
      similar models were grouped within continuous periods, designated as ignition
      based seasons. We found three ignition-based seasons in the Mediterranean region
      and five in the Atlantic zones, not coincidental with calendar seasons, but with
      a high degree of agreement with current legally designated operational fire
      seasons. Our results suggest that an additional late-winter-early-spring fire
      season in the Mediterranean area and the extension of this same season in the
      Atlantic zone should be re-considered for operational purposes in the future.

PMID- 29597112
TI  - We cannot change the past, but we can change its meaning. A randomized controlled
      trial on the effects of self-help imagery rescripting on depression.
AB  - BACKGROUND: Imagery rescripting is a psychotherapeutic technique that aims to
      ameliorate negative emotions by altering (i.e., rescripting) inner
      representations of negative memories and images. Although the treatment was
      initially developed for traumatized individuals, face-to-face interventions have
      yielded promising results for patients with other diagnoses as well. The present
      study explored the feasibility and efficacy of the approach when used as a self
      help intervention for depression. METHOD: A total of 127 individuals with
      diagnosed depression were randomly allocated to either a wait-list control
      condition or received a brief or long version of a manual teaching imagery
      rescripting. Six weeks after inclusion, patients were invited to participate in
      the post assessment. The Beck Depression Inventory (BDI-II) served as the primary
      outcome (registered at ClinicalTrials.gov (NCT03299127). RESULTS: The long
      version was superior to the wait-list control condition on the BDI-II, self
      esteem, and quality of life at a medium effect size. No effects emerged for
      anxiety. No significant between-group differences were found for the brief
      version. Moderation analyses indicated that the self-help approach seems
      particularly beneficial for those scoring high on symptoms, willingness to
      change, and expectancy (baseline). Most patients indicated they would use the
      technique in the future. DISCUSSION: The efficacy of imagery rescripting was
      confirmed when applied via self-help. Use of the long form of the manual is
      recommended. Future studies are needed to ascertain whether treatment effects are
      sustained over time.

PMID- 29597113
TI  - Estimation of radiocesium dietary intake from time series data of radiocesium
      concentrations in sewer sludge.
AB  - After the Fukushima accident, it became important to determine the quantity of
      radionuclide ingested by inhabitants. The most common methods currently used to
      obtain such data are the "market basket" (MB) and "duplicate" (DP) methods.
      However, it is difficult to conduct monitorings using these methods with
      sufficient frequency as they are high cost and time-consuming. The present study
      proposes a new method to estimate the ingestion of radionuclides, based on the
      time-dependent concentrations of radiocesium in sewer sludge, which addresses the
      uncertainties of the two common methods. The newly proposed method, which we
      designate as SL, consists of three steps: (1) the separation of wet weather and
      dry weather data, (2) determining the mass balance of the wastewater treatment
      plant (WWTP), and (3) developing a reverse biokinetic model to relate the amount
      of radionuclides ingested to the amounts contained in the sewer sludge. We tested
      the new method using the time-dependent radiocesium concentrations in sewer
      sludge from the WWTP in Fukushima City. The results from the SL method agreed to
      those from the MB while overestimated those from DP method. The trend lines for
      all three methods, however, are in good agreement. Sensitivity analyses of SL
      method indicate further studies on uncertainties of sensitive parameters are
      deemed necessary to improve the accuracy of the method.

PMID- 29597114
TI  - Synthesis, in vitro alpha-glucosidase inhibitory potential and molecular docking
      study of thiadiazole analogs.
AB  - alpha-Glucosidase is a catabolic enzyme that regulates the body's plasma glucose
      levels by providing energy sources to maintain healthy functioning. 2-Amino
      thiadiazole (1-13) and 2-amino-thiadiazole based Schiff bases (14-22) were
      synthesized, characterized by 1H NMR and HREI-MS and screened for alpha
      glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied
      degree of alpha-glucosidase inhibitory potential with IC50 values ranging between
      2.30 +/- 0.1 to 38.30 +/- 0.7 MUM, when compare with standard drug acarbose
      having IC50 value of 39.60 +/- 0.70 MUM. Among the series eight derivatives 1, 2,
      6, 7, 14, 17, 19 and 20 showed outstanding alpha-glucosidase inhibitory potential
      with IC50 values of 3.30 +/- 0.1, 5.80 +/- 0.2, 2.30 +/- 0.1, 2.70 +/- 0.1, 2.30
      +/- 0.1, 5.50 +/- 0.1, 4.70 +/- 0.2, and 5.50 +/- 0.2 MUM respectively, which is
      many fold better than the standard drug acarbose. The remaining analogs showed
      good to excellent alpha-glucosidase inhibition. Structure activity relationship
      has been established for all compounds. The binding interactions of these
      compounds were confirmed through molecular docking.

PMID- 29597115
TI  - Risk factors for musculoskeletal injury in elite pre-professional modern dancers:
      A prospective cohort prognostic study.
AB  - OBJECTIVES: To examine risk factors for injury in pre-professional modern
      dancers. DESIGN: With prospectively designed screening and injury surveillance,
      we evaluated four risk factors as categorical predictors of injury: i)
      hypermobility; ii) dance technique motor-control; iii) muscle tightness; iv)
      previous injury. Screening and injury data of 180 students enrolled in a
      university modern dance program were reviewed over 4-yrs of training. Dancers
      were divided into 3-groups based on predictor scores. Dance exposure was based on
      hours of technique classes/wk. Negative binomial log-linear analyses were
      conducted with the four predictors, p < 0.05. RESULTS: Dancers with low and high
      Beighton scores were 1.43 and 1.22 times more likely to sustain injury than
      dancers with mid-range scores (p <= 0.03). Dancers with better technique (low or
      medium scores) were 0.86 and 0.63 times less likely to sustain injury (p = 0.013
      and p < 0.001) compared to those with poor technique. Dancers with one or 2-4
      tight muscles were 2.7 and 4.0 times more likely to sustain injury (p <= 0.046).
      Dancers who sustained 2-4 injuries in the previous year were 1.38 times more
      likely to sustain subsequent injury (p < 0.001). CONCLUSIONS: This contributes
      new information on the value of preseason screening. Dancers with these risk
      factors may benefit from prevention programs.

PMID- 29597116
TI  - Elevated serum uric acid levels are associated with endothelial dysfunction in
      HIV patients receiving highly-active antiretroviral therapy.
AB  - BACKGROUND AND AIMS: Elevated serum uric acid (SUA) levels may be associated with
      endothelial dysfunction. Increased rates of metabolic syndrome (MS) and elevated
      SUA levels were described in human immunodeficiency virus (HIV) infected
      patients. We investigated whether SUA levels are associated with endothelial
      dysfunction in HIV positive patients receiving highly-active antiretroviral
      therapy (HAART) irrespective of MS. METHODS: In this cross-sectional study of 250
      HIV positive patients receiving stable HAART, we evaluated the relationship
      between MS, SUA levels and endothelial function. SUA levels and brachial artery
      flow-mediated dilation (bFMD) were measured. The relationship between logarithmic
      (LG)-transformed SUA levels and bFMD was evaluated after correction for MS.
      RESULTS: MS was detected in 28.4% of patients and elevated SUA levels (>=6 mg/dL)
      in 25.2%. MS was associated with higher LG-SUA levels (age-, gender- and
      glomerular filtration rate-adjusted beta = 0.204, p = 0.001). The crude linear
      association between LG-SUA levels and LG-bFMD (beta = -0.166, p = 0.008) was
      abolished after correction for MS (beta = -0.089, p = 0.172). When SUA levels
      were used as a categorical variable (>=6 mg/dL or <6 mg/dL and SUA quartiles,
      respectively), the association between LG-SUA levels and LG-bFMD remained
      significant after adjustment for MS (beta = -0.142, p = 0.022 and beta = -0.163,
      p = 0.010, respectively). CONCLUSIONS: MS significantly affects SUA levels in
      HAART-treated HIV infected patients. The negative association between SUA and
      bFMD is independent of MS only for elevated SUA levels.

PMID- 29597117
TI  - Native and myeloperoxidase-oxidized low-density lipoproteins act in synergy to
      induce release of resolvin-D1 from endothelial cells.
AB  - BACKGROUND AND AIMS: Oxidation of native low-density lipoproteins (LDLs-nat)
      plays an important role in the development of atherosclerosis. A major player in
      LDL-nat oxidation is myeloperoxidase (MPO), a heme enzyme present in azurophil
      granules of neutrophils and monocytes. MPO produces oxidized LDLs called Mox
      LDLs, which cause a pro-inflammatory response in human microvascular endothelial
      cells (HMEC), monocyte/macrophage activation and formation of foam cells.
      Resolvin D1 (RvD1) is a compound derived from the metabolism of the
      polyunsaturated fatty acid DHA, which promotes resolution of inflammation at the
      ng/ml level. METHODS: In the present study, we used liquid chromatography-mass
      spectrometry (LC-MS/MS) to investigate the synthesis of RvD1 and its precursors -
      17(S)-hydroxy docosahexaenoic acid (17S-HDHA) and docosahexaenoic acid (DHA) - by
      HMEC, in the presence of several concentrations of Mox-LDLs, copper-oxidized-LDLs
      (Ox-LDLs), and native LDLs or in mouse plasma. The LC-MS/MS method has been
      validated and applied to cell supernatants and plasma to measure production of
      RvD1 and its precursors in several conditions. RESULTS: Mox-LDLs played a
      significant role in the synthesis of RvD1 and 17S-HDHA from DHA compared to Ox
      LDLs. Moreover, Mox-LDLs and LDLs-nat acted in synergy to produce RvD1. In
      addition, different correlations were found between RvD1 and M1 macrophages, age
      of mice or Cl-Tyr/Tyr ratio. CONCLUSIONS: These results suggest that although Mox
      LDLs are known to be pro-inflammatory and deleterious in the context of
      atherosclerosis, they are also able to induce a pro-resolution effect by
      induction of RvD1 from HMEC. Finally, our data also suggest that HMEC can produce
      RvD1 on their own.

PMID- 29597118
TI  - Risk analysis of technological hazards: Simulation of scenarios and application
      of a local vulnerability index.
AB  - The potential impact of a technological accident can be assessed by risk
      estimation. Taking this into account, the latent or potential condition can be
      warned and mitigated. In this work we propose a methodology to estimate risk of
      technological hazards, focused on two components. The first one is the processing
      of meteorological databases to define the most probably and conservative scenario
      of study, and the second one, is the application of a local social vulnerability
      index to classify the population. In this case of study, the risk was estimated
      for a hypothetical release of liquefied ammonia in a meat-packing industry in the
      city of La Plata, Argentina. The method consists in integrating the simulated
      toxic threat zone with ALOHA software, and the layer of sociodemographic
      classification of the affected population. The results show the areas associated
      with higher risks of exposure to ammonia, which are worth being addressed for the
      prevention of disasters in the region. Advantageously, this systemic approach is
      methodologically flexible as it provides the possibility of being applied in
      various scenarios based on the available information of both, the exposed
      population and its meteorology. Furthermore, this methodology optimizes the
      processing of the input data and its calculation.

PMID- 29597119
TI  - Assessment of membrane photobioreactor (MPBR) performance parameters and
      operating conditions.
AB  - Membrane photobioreactor (MPBR) technology is an emerging algae-based wastewater
      treatment system. Given the limitations due to the general use of conventional
      analytical approaches in previous research, this study aims to provide a more
      comprehensive assessment of MPBR performance through advanced characterisation
      techniques. New performance parameters are also proposed, encompassing five
      important aspects of MPBR system efficiency (i.e. biomass concentration,
      composition, production, nutrient uptake and harvesting potential). Under initial
      standard operating conditions, performance parameters, such as cell count/MLSS
      ratio, cell viability, proportion of bacteria and biomass yield coefficient, were
      found to offer new insights into the operation of MPBR. These parameters were
      then used, for the first time, to systematically investigate MPBRs operated under
      different hydraulic retention times (HRTs) and solids retention times (SRTs).
      Applying shorter HRT and SRT was observed to increase cell viability and
      productivity (up to 0.25 * 107 cells/mL.d), as anticipated due to the higher
      nutrient loading. It was noted that the faster growing algal cells featured lower
      requirement for nutrients. On the other hand, extending HRT and SRT resulted in a
      more heterogeneous culture (lower cell count/MLSS ratio and higher proportion of
      bacteria), achieving a higher degree of autoflocculation and greater NO3-N and
      PO4-P removals of up to 79% and 78% respectively. The results demonstrate the
      trade-off between applying different HRTs and SRTs and the importance of fully
      characterising system performance to critically assess the advantages and
      limitations of chosen operating conditions.

PMID- 29597120
TI  - Highly effective enhancement of waste activated sludge dewaterability by altering
      proteins properties using methanol solution coupled with inorganic coagulants.
AB  - Proteins are the dominant organic component of extracellular polymeric substances
      (EPS) in waste activated sludge (WAS), and play an important role during sludge
      dewatering processes. Methanol is a polar hydrophilic reagent and can denature
      proteins, which suggested to us that the modification of protein configurations
      with methanol could improve sludge dewatering performance. In this study,
      methanol was used to precondition WAS prior to adding inorganic coagulants for
      dewatering enhancement. The morphology and EPS properties (especially of
      proteins) were investigated to analyze and explain the effects of methanol in the
      sludge conditioning process. The results show that methanol performed much better
      than traditional inorganic coagulants in improving sludge dewaterability in term
      of specific resistance to filtration (SRF) and cake solid content (CSC).
      Extractable proteins in EPS increased to a maximum when the concentration of
      methanol reached 40% (w/w) because cell membranes were destroyed and
      intracellular substances and water were released. Floc protein content was
      reduced with the further increase in methanol concentration due to protein
      precipitation. Confocal laser scanning microscopy analysis indicated that
      proteins precipitated and formed larger aggregates because methanol destroyed
      both the hydration shell and the hydrophobic clusters of proteins and expanded
      the protein tertiary structure to release interstitial water and bound water. The
      combination treatment of methanol and inorganic coagulants (PAC or FeCl3) showed
      significant synergetic effects on enhancing sludge dewatering and cake drying. In
      practical applications, methanol from the dewatering sludge can be returned to
      the biochemical pool and used as the carbon source for nitrogen removal in the
      denitrification process. This integrated process is appropriate for sludge final
      disposal technologies that have high energy demands, such as incineration and
      pyrolysis. This paper describes a novel approach to improving sludge
      dewaterability through the alteration of protein properties by use of
      physiochemical techniques.

PMID- 29597121
TI  - Short term protein supplementation during a long interval prostaglandin-based
      protocol for timed AI in sheep.
AB  - The aim of this study was to evaluate the reproductive impact of a short-term
      protein supplementation on a long interval prostaglandin-based protocol (two PG
      injections 15 d apart; PG15) for timed artificial insemination in sheep. During
      the breeding season, 437 multiparous Merino ewes grazing native pastures (forage
      allowance of 6 kg of dry matter/100 kg of live weight; crude protein: 10.8%,
      metabolic energy: 2.1 Mcal/kg of dry matter) were selected. Ewes were allocated,
      according to body condition score (3.2 +/- 0.2) and body weight (40.6 +/- 4.9 kg,
      mean +/- SD), to a 2 * 2 factorial design: type of estrus -spontaneous estrus
      (SE) or induced with PG15 (PG15)-, and supplementation (yes or no) before
      insemination (+FF; soybean meal at Days -10 to -3; crude protein: 51.9%,
      metabolic energy: 2.8 Mcal/kg of dry matter; average consumption 0.9% live
      weight/ewe/day of dry matter). All ewes were cervically artificial inseminated
      (Day -2 to -3 in SE ewes at estrus detection; Day 0 = timed artificial
      insemination in PG15 ewes). Ovulation rate on Day 7, non-return to service on Day
      23, conception, fertility, prolificacy and fecundity on Day 60 were evaluated.
      Ovulation rate (1.17 +/- 0.40 vs. 1.06 +/- 0.25), non-return to service at Day 23
      (81.7 vs. 64.2%), conception (78.8 vs. 61.5%), fertility (75.2 vs. 61.5%) and
      fecundity (0.77 vs. 0.62) were higher in ewes from SE than PG15 group (P < 0.05).
      However, no differences were observed in prolificacy (1.02 +/- 0.16 vs. 1.01 +/-
      0,12) between groups (P > 0.05). Protein supplementation increased ovulation rate
      (1.30 +/- 0.45 vs. 1.17 +/- 0.40), prolificacy (1.18 +/- 0.39 vs. 1.02 +/- 0.16)
      and fecundity (0.94 vs. 0.77%; P < 0.05), but not non-return to service on Day 23
      (83.8 vs. 81.7%), conception (82.9 vs. 78.8%) or fertility (79.1 vs. 75.2%; P >
      0.05) in SE group. The supplement feed to PG15 ewes increased ovulation rate
      (1.35 +/- 0.45 vs. 1.06 +/- 0.25), prolificacy (1.25 +/- 0.43 vs. 1.01 +/- 0.12)
      and fecundity (0.79 vs. 0.62%; P < 0.05) to levels comparable to SE + FF ewes (P
      > 0.05). The magnitude of the increase in ovulation rate in PG15 was greater than
      in the SE group (27 vs. 11%; P < 0.05). However, non-return to service on Day 23
      (65.1 vs. 64.2%), conception (63.3 vs 61.5%), and fertility rate (63.3 vs. 61.5%;
      P < 0.05) remained similar in PG15 supplemented or not supplemented ewes. In
      conclusion, a short-term protein supplementation before cervical time artificial
      insemination improved the reproductive performance of ewes synchronized with the
      PG15 protocol to levels comparable to the SE group.

PMID- 29597122
TI  - In vitro sperm quality and DNA integrity of SexedULTRATM sex-sorted sperm
      compared to non-sorted bovine sperm.
AB  - SexedULTRATM is an improved method of sex-sorting sperm creating a less damaging
      environment to retain sperm integrity through the sorting process. The aim of
      this study was to evaluate the in vitro characteristics of fresh and frozen
      bovine sperm using the SexedULTRATM method, and compare it to conventional (non
      sorted) sperm. For both methods, percent total sperm motility was estimated
      visually and also classified into total and progressively motile using a computer
      assisted sperm analyzer (CASA). Percent sperm with intact plasma membranes (VIA)
      and acrosomes (PIA) were assessed using flow cytometry and sperm DNA
      fragmentation index (DFI) was estimated using the Bull sperm Halomax(r) Kit. Two
      contemporaneous ejaculates from 10 bulls were processed and cryopreserved using
      one of the two procedures (SexedULTRATM and conventional). Sperm motility, VIA
      and PIA were assessed post-thaw (0 h) and post-incubation (3 h at 37  degrees C,
      8 h and 24 h at 18  degrees C). DFI was analyzed post-thaw (0 h) and after 6, 24,
      48 and 72 h of incubation at 37  degrees C. In a second experiment, ejaculates
      from 7 bulls were split sampled into the two types of processing (SexedULTRATM
      and conventional) and diluted using a fresh semen extender developed for sex
      sorted bovine sperm. Sperm quality was assessed after dilution (0 h) and after
      incubation for 12, 24, 48, 72 h at 18 degrees , and the same time points of
      incubation at 37  degrees C for DFI. Frozen-thawed SexedULTRATM sperm was
      significantly (P < 0.05) better than conventional semen after a 3 h incubation at
      37  degrees C for PIA, and after a 24 h incubation at 18  degrees C for percent
      visual motility and PIA. DFI was significantly lower for SexedULTRATM compared to
      conventional at all time points of incubation (37  degrees C). Fresh SexedULTRATM
      sperm showed improved quality compared to conventional at all time points of
      incubation at 18  degrees C for percent visual and total motile sperm, VIA, PIA,
      and DFI. Significant differences were also found in progressive motile sperm
      immediately after dilution (0 h), but not at any time point after incubation. The
      results show that the SexedULTRATM process maintains the quality of sex-sorted
      sperm and, in many cases, has better in vitro longevity than conventional semen.

PMID- 29597123
TI  - Systemic profiling of ectopic fat deposits in the reproductive tract of dairy
      cows.
AB  - During the transition period, high-yielding dairy cows suffer from negative
      energy balance, intense lipomobilization and impaired lipid metabolism; this
      metabolic condition can lead to overburdened triglycerides accumulation in the
      liver, known as liver lipidosis, which has been associated to impaired fertility
      in dairy cows. The mechanisms of this impairment can be in principle correlated
      with the presence and the extent of ectopic fat depots. However, current methods
      for evaluating fat accumulation in liver and in the reproductive tract suffer
      from low resolution, sensitivity, and specificity. Confocal microscopes are
      equipped with Gallium arsenide phosphide detectors, thus enabling the acquisition
      of intense signals from tissue biopsies. This method could differentiate whether
      fat deposition occurred without requiring sample sectioning. Here, we examined
      with this technique liver, uterine and ovarian samples of heifers and regularly
      slaughtered repeat breeder and overconditioned dairy cows, to quantify lipid
      droplets and depots at a submicrometer scale with high specificity. With the aid
      of this technique, we found lipid depots in uterine and ovarian specimens.
      Moreover, we found that the size and number of depots increased with the degree
      of liver lipidosis. Further studies are needed to elucidate the relationship
      between the severity and extent of these deposits and the fertility of lactating
      dairy cows. Since tissues other than liver display different characteristic lipid
      droplet distributions, this technique can be potentially employed to shed new
      light on the pathogenesis of lipidosis and to assess new risk factors for
      infertility.

PMID- 29597124
TI  - Plasma IGF-I, INSL3, testosterone, inhibin concentrations and scrotal
      circumferences surrounding puberty in Japanese Black beef bulls with normal and
      abnormal semen.
AB  - The relationships between semen abnormalities and peripheral concentrations of
      testicular and metabolic hormones in beef bulls are unclear. Here we compared
      plasma insulin-like growth factor I (IGF-I), insulin-like peptide 3 (INSL3),
      testosterone, inhibin concentrations, and scrotal circumferences surrounding
      puberty in Japanese Black beef bulls (n = 66) with normal or abnormal semen. We
      collected blood samples and measured scrotal circumferences monthly from 4 to 24
      months of age. Semen was collected weekly from 12 months until at least 18 months
      of age. Fresh semen was evaluated for semen volume, sperm motility,
      concentrations, and morphological defects. The normal fresh semen was frozen by a
      standard method and examined for post-thaw sperm motility and fertility. Bulls
      were classified as having either normal post-thaw semen (n = 45) or abnormal
      semen (n = 21, when at least one of the above test items was abnormal for 6
      months). Abnormal semen was classified into abnormal fresh or low-fertility post
      thaw which evaluated for rates of transferable embryos. The abnormal fresh was
      categorized as having sperm morphological defects, low motility, and
      morphological defects plus low motility. Scrotal circumferences were smaller for
      the abnormal-semen group vs. the normal-semen group at 20 and 24 months (p <
      0.05). Plasma IGF-I, INSL3, and inhibin concentrations in the abnormal-semen
      group were lower than those of the normal-semen group (p < 0.05) surrounding
      puberty (4-6, 8, 18-22, and 24 months for IGF-I; 6, 9, 11-14, 17, and 20-21
      months for INSL3; 5, 8-13, 16, 17, 19, and 20 months for inhibin). The plasma
      testosterone concentrations were lower in the abnormal-semen bulls vs. normal
      semen bulls only at 22 months (p < 0.05). Analyses of the classified abnormal
      semen showed lower plasma INSL3 concentrations for morphological defects plus low
      motility in fresh semen (p < 0.05) and lower IGF-I and inhibin concentrations for
      low-fertility post-thaw semen (p < 0.05) compared to the normal semen. Our
      results suggest that reduced secretions of IGF-I, INSL3, and inhibin surrounding
      puberty may be associated with semen aberration in beef bulls. Notably, the
      combined sperm abnormality of morphological defects and low motility in fresh
      semen could involve lowered INSL3, whereas the low-fertility post-thaw semen
      might be related to decreases of IGF-I and/or inhibin. Pre-puberty blood IGF-I,
      INSL3 and inhibin concentrations could be used as indicators to predict aberrant
      semen in beef bulls.

PMID- 29597125
TI  - The anti-inflammatory effect of exogenous lactoferrin on breeding-induced
      endometritis when administered post-breeding in susceptible mares.
AB  - The deposition of semen into the uterus of the horse induces a transient innate
      immune response that lasts 24-36 h in the normal mare. There exists a subset of
      mares that are unable to resolve this inflammation in a timely manner, and are
      classified as susceptible to the disease of persistent breeding-induced
      endometritis (PBIE). Lactoferrin is a protein of interest as a potential
      therapeutic for this persistent inflammation due to its anti-inflammatory and
      bactericidal properties. The addition of human recombinant lactoferrin (hrLF) to
      the insemination dose was previously shown to suppress mRNA expression of the pro
      inflammatory cytokine tumor necrosis factor (TNF)-alpha at 6 h after
      insemination, but no studies have shown the effect of lactoferrin when infused
      post-breeding. Therefore, the objectives of this study were to (1) assess the
      safety of intra-uterine infusion of hrLF, (2) evaluate the effect of intrauterine
      infusion of hrLF post-breeding as a modulator of the immune response to breeding
      in the susceptible mare, and (3) determine the most effective concentration of
      hrLF. For the first experiment four normal mares received an intrauterine
      infusion of 500 MUg/mL hrLF resuspended in 10 mL lactated Ringer's solution (LRS)
      and heart rate, rectal temperature, respiration, and endometrial quality were
      evaluated. For the second experiment, six mares classified as susceptible to PBIE
      were bred during estrus with 500 * 106 progressively motile sperm comprised of
      the ejaculates from two stallions, which were centrifuged over Androcoll-E to
      remove seminal plasma. Each insemination dose was resuspended in 30 mL LRS. Six
      hours after breeding, a 1L LRS uterine lavage was performed prior to treatments.
      Four treatments were administered over four consecutive estrous cycles in
      randomized order of: 10 mL LRS (vehicle control), 50 MUg/mL hrLF resuspended in
      10 mL LRS, 250 MUg/mL hrLF resuspended in 10 mL LRS, and 500 MUg/mL hrLF
      resuspended in 10 mL LRS. Twenty-four hours after breeding the mares were
      evaluated via transrectal ultrasonography for fluid retention. A low volume
      uterine lavage (250 mL LRS) was performed and the effluent was evaluated for
      polymorphonuclear neutrophils (PMNs). Finally, an endometrial biopsy was obtained
      for qPCR analysis of selected inflammatory cytokines. Lactoferrin had no
      significant overall effect on vital signs or endometrial quality. The addition of
      hrLF (50 MUg/mL, 250 MUg/mL, 500 MUg/mL) did not significantly affect the amount
      of fluid detected post-breeding, but suppressed the ratio of PMNs to epithelial
      cells at all three concentrations compared to controls. In addition, all three
      concentrations of hrLF increased the mRNA expression of the anti-inflammatory
      cytokine interleukin-1 receptor antagonist (IL-1RN), while the 50 MUg/mL dose
      significantly suppressed mRNA expression of the pro-inflammatory cytokine
      interferon gamma (IFNgamma). In conclusion, the infusion of hrLF post-breeding
      was found to modulate the inflammatory response to breeding in the mare, and
      appears to be most effective at the 50 MUg/mL concentration.

PMID- 29597126
TI  - Preparation of polymeric Janus microparticles with hierarchically porous
      structure and enhanced anisotropy.
AB  - Anisotropic Janus particles are of great interest for many applications. It is
      well known that behavior and utility of Janus particles are highly dependent on
      their chemistry and geometry. Herein, we report the synthesis of monodisperse
      polymeric Janus microparticles that were anisotropic not only in chemistry and
      shape but also in surface morphology and porosity, via a modified seeded
      polymerization technique. Chemical composition, shape, morphology and porosity of
      the polymeric Janus microparticles were flexibly controlled by utilizing
      different quantities and species of monomer and porogen. The polymeric Janus
      microparticles exhibited hierarchically porous structure, including micro- and
      meso-pores as evidenced by isothermal nitrogen adsorption and desorption. Due to
      the high specific surface area, anisotropy of the polymeric Janus microparticles
      was enhanced according to the greater fluorescence contrast on distinct sides of
      the polymeric Janus microparticles. Moreover, swelling and phase-separation
      processes of cross-linked seeds were in situ observed on an optical microscope to
      demonstrate the formation mechanism of the polymeric Janus microparticles.

PMID- 29597127
TI  - Viscoelastic diamine surfactant for stable carbon dioxide/water foams over a wide
      range in salinity and temperature.
AB  - HYPOTHESIS: The viscosity and stability of CO2/water foams at elevated
      temperature can be increased significantly with highly viscoelastic aqueous
      lamellae. The slow thinning of these viscoelastic lamellae leads to greater foam
      stability upon slowing down Ostwald ripening and coalescence. In the aqueous
      phase, the viscoelasticity may be increased by increasing the surfactant tail
      length to form more entangled micelles even at high temperatures and salinity.
      EXPERIMENTS: Systematic measurements of the steady state shear viscosity of
      aqueous solutions of the diamine surfactant (C16-18N(CH3)C3N(CH3)2) were
      conducted at varying surfactant concentrations and salinity to determine the
      parameters for formation of entangled wormlike micelles. The apparent viscosity
      and stability of CO2/water foams were compared for systems with viscoelastic
      entangled micellar aqueous phases relative to those with much less viscous
      spherical micelles. FINDINGS: We demonstrated for the first time stable CO2/water
      foams at temperatures up to 120  degrees C and CO2 volumetric fractions up to
      0.98 with a single diamine surfactant, C16-18N(CH3)C3N(CH3)2. The foam stability
      was increased by increasing the packing parameter of the surfactant with a long
      tail and methyl substitution on the amine to form entangled viscoelastic wormlike
      micelles in the aqueous phase. The foam was more viscous and stable compared to
      foams with spherical micelles in the aqueous lamellae as seen with C12-14N(EO)2
      and C16-18N(EO)C3N(EO)2.

PMID- 29597128
TI  - Generation of an induced pluripotent stem cell (iPSC) line from a patient with
      maturity-onset diabetes of the young type 3 (MODY3) carrying a hepatocyte nuclear
      factor 1-alpha (HNF1A) mutation.
AB  - Heterozygous non-synonymous (p.S142F) mutation in HNF1A leads to maturity-onset
      diabetes of the young (MODY) type 3, which is a subtype of dominant inherited
      young-onset non-autoimmune diabetes due to the defect of insulin secretion from
      pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a
      patient with HNF1A p.S142F mutation. Cells from this patient, which were
      reprogrammed by non-integrative viral transduction had normal karyotype,
      harboured the HNF1A p.S142F mutation, expressed pluripotency hallmarks.

PMID- 29597129
TI  - The effects of plasma gelsolin on human erythroblast maturation for erythrocyte
      production.
AB  - Gelsolin is an actin binding protein present in blood plasma and in cytoplasm of
      cells including macrophages. Gelsolin has important functions in cell cycle
      regulation, apoptotic regulation, and morphogenesis. Even though bone marrow
      macrophages and serum factors are critical for regulating erythropoiesis, the
      role of gelsolin on human erythroblasts has not been studied. Here, we
      investigated the effects of human recombinant plasma gelsolin (pGSN) on human
      immature erythroblasts. CD34+ cells isolated from cord blood were differentiated
      into erythroid cells in serum-free medium. When pGSN was applied to the culture
      medium, it accelerated basophilic and polychromatic erythroblast maturation and
      increased the enucleation rate with highly expressed erythropoiesis-related
      mRNAs. Also, pGSN was effective in reducing dysplastic changes caused by
      vincristine, suggesting its role in cell cycle progression at G2/M checkpoints.
      Also, pGSN activated caspase-3 during maturation stages in which caspase-3
      functions as a non-apoptotic maturational signal or a pro-apoptotic signal
      depending on maturation stages. Our results suggest that pGSN has a pivotal role
      in maturation of erythroblasts and this factor might be one of the way how bone
      marrow macrophages and previously unknown serum factors work to control
      erythropoiesis. pGSN might be used as additive for in vitro production of
      erythrocytes.

PMID- 29597130
TI  - MicroRNA co-expression patterns unravel the relevance of extra cellular matrix
      and immunity in breast cancer.
AB  - BACKGROUND: Aberrant microRNA (miRNA) expression is associated with human tumors,
      including breast cancer (BC), and has diagnostic and therapeutic potential. BC
      tissue is characterized by distinctive miRNA signatures associated with cancer
      development or progression. METHODS: We explored miRNA profiles from BC tissues
      by unsupervised hierarchical clustering. Functional analysis was based on miRNA
      mRNA data integration and Gene Set Enrichment Analysis. RESULTS: Partition of
      miRNA expression data from BC samples of Chinese Han and Caucasian subjects
      identified clusters of correlated miRNAs that were subjected to a global and
      integrative analysis aimed at identifying novel associations with biological and
      clinical value. Co-expression of miRNAs clustered in the same module was
      partially explained by co-transcription of the same genomic locus or involvement
      in similar biological functions. No significant associations were found among
      miRNA clusters and clinical-pathological variables, except for ER status and
      immune infiltration estimated by CIBERSORT. A large number of miRNA clusters,
      instead, were significantly differentially expressed in PAM 50 and extracellular
      matrix (ECM) subgroups. Specifically, a new cluster including several relatively
      new miRNAs was overexpressed in ECM3 tumors, characterized by increased
      epithelial to mesenchymal transition (EMT). An integrative approach to extract
      meaningful relationships on miRNA/mRNA networks and predict the functional role
      of the miRNA clusters indicates that immune system, ECM, proliferation,
      transcription and DNA repair were the biological functions more targeted by
      miRNAs aberrantly expressed in BC. CONCLUSIONS: We then identified novel miRNA
      patterns associated with BC molecular features, and described a complex
      regulatory network where miRNAs belonging to the same module cooperate in finely
      tuning gene expression.

PMID- 29597132
TI  - Finite element modeling of trolling-mode AFM.
AB  - Trolling mode atomic force microscopy (TR-AFM) has overcome many imaging problems
      in liquid environments by considerably reducing the liquid-resonator interaction
      forces. The finite element model of the TR-AFM resonator considering the effects
      of fluid and nanoneedle flexibility is presented in this research, for the first
      time. The model is verified by ABAQUS software. The effect of installation angle
      of the microbeam relative to the horizon and the effect of fluid on the system
      behavior are investigated. Using the finite element model, frequency response
      curve of the system is obtained and validated around the frequency of the
      operating mode by the available experimental results, in air and liquid. The
      changes in the natural frequencies in the presence of liquid are studied. The
      effects of tip-sample interaction on the excitation of higher order modes of the
      system are also investigated in air and liquid environments.

PMID- 29597131
TI  - Health-related quality of life and utility scores of patients with breast
      neoplasms in China: A multicenter cross-sectional survey.
AB  - BACKGROUND: Health-related quality of life and utility scores of patients with
      breast cancer and precancerous lesions are sparse in China. This study aimed to
      derive utility scores of patients with breast cancer and precancer in China.
      MATERIAL AND METHODS: An interviewer-administered cross-sectional survey was
      conducted in 12 provinces across China from 2013 to 2014. The three-level EuroQol
      5-Dimension instrument was used to evaluate quality of life, and utility scores
      were generated using the Chinese value set. Univariate and multivariate analyses
      were performed to explore the determinants of utility scores. RESULTS: In total,
      2626 breast cancer and 471 precancer patients were included. Mean age was 49.1
      for breast cancer and 41.4 years for precancer (p < 0.001). Among the five
      dimensions, pain/discomfort was the most reported problem, 53.9% in breast cancer
      and 29.3% in precancer patients. Mean (95% CI) utility scores for breast cancer
      and precancer patients were estimated as 0.887 (0.875-0.899) and 0.781 (0.774
      0.788), and the scores of breast cancer at stage-I, stage-II, stage-III and stage
      IV were 0.789 (0.774-0.805), 0.793 (0.783-0.802), 0.774 (0.759-0.788) and 0.686
      (0.654-0.717), respectively. Mean (95% CI) visual analogue scale scores for
      breast cancer and precancer were 75.6 (74.0-77.3) and 72.8 (72.3-73.3). Multiple
      regression showed advanced clinical stage, lower educational level, lower
      household income, surgery treatment, and undergoing treatment were independently
      associated with lower utility scores for breast cancer patients. CONCLUSION: The
      utility scores deteriorate with the severity of breast neoplasms. Detailed
      utility scores of breast cancer and precancer are fundamental for further cost
      utility analysis in China.

PMID- 29597133
TI  - Changes in the prevalence of comorbidity in the Australian population with
      cancer, 2007-2014.
AB  - BACKGROUND: Coexistence of multiple chronic diseases is highly prevalent among
      the cancer population. This study aims to assess changes in the prevalence of
      chronic conditions among the population with cancer compared to the Australian
      general population between 2007 and 2014. METHODS: Data from three successive
      National Health Surveys conducted by the Australian Bureau of Statistics between
      2007 and 2014 were utilized. Comparisons were made between the samples of the
      Australian population aged 25 years and above with a history of cancer and those
      respondents who did not report having had a cancer using logistics regression
      models. RESULTS: People with a history of cancer had significantly higher odds of
      reporting non-infectious comorbidity compared to the non-cancer groups across the
      three surveys. There were no significant changes in the prevalence of diseases
      affecting circulatory, musculoskeletal, digestive, nervous system, blood and
      blood forming organs, eye, skin and infectious and parasitic diseases over time
      among the population with cancer. The prevalence of mental and behavioural
      problems, endocrine, nutritional and metabolic diseases, and diseases of
      respiratory and genitourinary system has increased over time among the cancer
      survivors. CONCLUSION: Comorbidity is more prevalent among the cancer population
      than the general population without cancer. The prevalence of comorbidity was
      fairly stable for most but not all comorbidities in the population with cancer
      over the eight-year study period. Further studies on the impacts of coordinated
      care models for the management of multi-morbidity experienced by cancer survivors
      that align with the 'National Strategic Framework for Chronic Conditions' are
      needed.

PMID- 29597134
TI  - Hyaluronic acid coated albumin nanoparticles for targeted peptide delivery in the
      treatment of retinal ischaemia.
AB  - Recent studies have shown that Connexin43 mimetic peptide (Cx43 MP) can prevent
      secondary damage following retinal ischaemic and inflammatory disorders by
      blocking uncontrolled Cx43 hemichannel opening. However, limitations in peptide
      stability and the presence of various intraocular barriers limit efficient
      retinal delivery in the clinical setting. The present study aimed to achieve
      targeted and sustained peptide delivery to the retina by encapsulating Cx43 MP
      into hyaluronic acid (HA) coated albumin nanoparticles (NPs). Intraocular
      biodistribution, particle retention, retinal targeting, and therapeutic efficacy
      of intravitreally injected NPs encapsulating Cx43 MP were evaluated in a rat
      model of retinal ischaemia-reperfusion injury. NPs rapidly diffused through the
      vitreous and specifically targeted CD44-expressing retinal cells. NPs remained at
      the target site for extended periods enabling sustained peptide release and thus
      prolonged therapeutic action. Compared to free Cx43 MP, Cx43 MP loaded NPs
      enabled enhanced therapeutic efficacy preventing thinning of retinal layers and
      disruption of retinal blood vessels. Immunohistochemical results confirm that
      Cx43 MP loaded NPs efficiently reduced Cx43 expression, thereby suppressing
      ongoing inflammation and preventing the loss of retinal ganglion cells. Overall,
      HA coated NPs could have great potential as a peptide delivery platform in the
      treatment of chronic retinal degenerative and inflammatory disorders.

PMID- 29597135
TI  - Direct matching methods for coils and preamplifiers in MRI.
AB  - In this paper, direct matching methods for coils and preamplifiers in receiver
      arrays are presented. Instead of compensating the reactance of the input
      impedance of preamplifiers, in our method, the reactance was used to resonate
      with the coil matching networks and thus to decouple the coils. Furthermore, coil
      matching networks and preamplifier input matching networks were combined, meaning
      the coil loop can be matched to the transistor in the preamplifier directly.
      These matching methods and, for comparison, the conventional matching method were
      implemented with custom-made preamplifiers and coils. Decoupling and noise
      matching performance were compared between these three configurations. Phase
      shifting networks between coils and preamplifiers are not necessary in our
      matching methods. With fewer components, these matching networks showed lower
      noise factors, while similar preamplifier-decoupling performance was found for
      all three methods.

PMID- 29597136
TI  - Intolerance for smoking abstinence among nicotine-deprived, treatment-seeking
      smokers.
AB  - INTRODUCTION: The Intolerance for Smoking Abstinence Discomfort Questionnaire
      (IDQ-S) assesses distress tolerance specific to nicotine withdrawal. Though
      developed to assess withdrawal-related distress, the IDQ-S has not been validated
      among nicotine-deprived, treatment-seeking smokers. The present study extended
      previous research by examining the predictive utility of the IDQ-S among
      abstinent, motivated-to-quit smokers. METHODS: Abstinent, treatment-seeking
      smokers completed the IDQ-S Withdrawal Intolerance and Lack of Cognitive Coping
      scales, assessments of nicotine dependence and reinforcement, and smoking history
      at baseline. At baseline and at 24-h, 2-week, and 1-month follow-up, participants
      completed a smoking cue-reactivity task (collection of cue-elicited craving and
      negative affect), and assessments of cigarettes per day (CPD; daily diaries at
      follow-up), carbon monoxide (CO), and cotinine. RESULTS: Greater IDQ-S Withdrawal
      Intolerance was associated with younger age, higher nicotine dependence and
      reinforcement, and less smoking years (ps < .03). Greater IDQ-S Lack of Cognitive
      Coping was associated with less education, lower nicotine dependence and
      reinforcement, higher baseline CPD, and no prior quit attempts (ps < .04). IDQ-S
      scales did not significantly predict cue-elicited craving or negative affect,
      CPD, CO, or cotinine levels at follow-up (ps > .10). CONCLUSIONS: Withdrawal
      intolerance and lack of cognitive coping did not predict smoking outcomes among
      nicotine-deprived, treatment-seeking smokers, but were associated with smoking
      characteristics, including nicotine dependence and reinforcement. Withdrawal
      intolerance and lack of cognitive coping may not be especially useful in
      predicting craving and smoking behavior, but future studies should replicate the
      present study's findings and assess the stability of the IDQ-S before forming
      firm conclusions about its predictive utility.

PMID- 29597137
TI  - Antibacterial activity of acidified sodium benzoate against Escherichia coli
      O157:H7, Salmonella enterica, and Listeria monocytogenes in tryptic soy broth and
      on cherry tomatoes.
AB  - Concerns about undesirable by-products from chlorine sanitation of fresh produce
      and the limited efficacy with the presence of organic matter, have led to studies
      on alternative washing solutions. The aim of this study was to evaluate the
      antibacterial activities of acidified sodium benzoate (NaB) solutions against
      Escherichia coli O157:H7, Salmonella enterica and Listeria monocytogenes in
      growth medium and on cherry tomatoes. Experimentally, the minimum inhibitory
      concentrations (MICs) and minimum bactericidal concentrations (MBCs, >3 Log
      reduction) of NaB against E. coli O157:H7 ATCC 43895, S. Enteritidis, and L.
      monocytogenes Scott A were determined at pH 7.0-4.0 using micro-broth dilution
      method and agar plating method, respectively. The reduction of the three bacteria
      in tryptic soy broth (TSB) by 500 and 1000 ppm NaB at pH 2.0, 2.5 and 3.0 for 30
      min at 21  degrees C was compared. Residual bacterial cocktails inoculated on
      cherry tomatoes were determined after soaking in 3000 ppm NaB solution adjusted
      to pH 2.0 for 3 min at 21  degrees C. Results showed that the MBC of NaB reduced
      from >10,000 ppm at pH 7.0 to 1000 ppm at pH 4.0 and was identical for the three
      bacteria. The log reduction of bacteria in TSB indicated that 1000 ppm NaB at pH
      2.0 was the most effective in killing the three pathogens. The respective
      reduction of E. coli O157:H7 and S. enterica cocktails inoculated on cherry
      tomatoes immersed in 3000 ppm NaB (pH 2.0) at 21  degrees C for 3 min was 4.99 +/
      0.57 and 4.08 +/- 0.65 log CFU/g, which was significantly higher (p < 0.05) than
      the treatments of 200 ppm free chlorine at pH 6.5. Conversely, the reduction of
      L. monocytogenes on tomatoes by 3000 ppm NaB (4.88 +/- 0.73 log CFU/g) was
      similar (p > 0.05) to 200 ppm chlorine. Furthermore, the reduction of bacterial
      cocktails on tomatoes by 3000 ppm NaB at pH 2.0 was not affected after adding 1%
      tomato puree, and bacteria were not detected in NaB washing solutions with and
      without 1% tomato puree and on following un-inoculated tomatoes. This study
      showed that acidified NaB solution may be used as an alternative post-harvest
      wash of produce.

PMID- 29597138
TI  - Rapid eye movement sleep behavior disorder or epileptic seizure during sleep? A
      video analysis of motor events.
AB  - PURPOSE: To compare the motor semiology of sleep behavior disorder (RBD) during
      rapid eye movement (REM) with epileptic seizures in non-REM and REM sleep.
      METHODS: We analyzed the types and frequency of motor events from videos of
      patients with RBD (n = 15, mean age 64.8 years, 179 motor episodes) and patients
      with epilepsy (n = 15, mean age 34.4 years, 87 sleep-related epileptic seizures
      including 34 during REM sleep). RESULTS: Patients with sleep-related epileptic
      seizures more often woke up abruptly (28% vs. 0.3%), raised head/trunk (31% vs.
      1.6%), opened their eyes (89% vs. 5%), had whole body movements (74% vs. 14%) or
      dystonic posturing (29% vs. 1.3%), manipulated objects in their environment (44%
      vs. 3.9%), as if emerging from sleep with ictal automatisms, and sniffed,
      coughed, or breathed differently during motor events. In contrast, RBD patients
      more often remained lying down with closed eyes (99% vs. 78%) as if still asleep,
      with non-stereotyped jerky movements (42% vs. 8%) and outward-directed behaviors
      (14% vs. 2%) than patients with epilepsy. There were no differences in violent
      behaviors and vocalizations between groups. Comparison with subgroups of REM or
      non-REM sleep seizures yielded many similar findings. CONCLUSION: These different
      motor patterns discriminate between RBD events and sleep-associated seizures, and
      could be used as an aid to differential diagnosis.

PMID- 29597139
TI  - Microbial effectors and the role of water and sugar in the infection battle
      ground.
AB  - Phytopathogenic microbes multiply in the apoplast-a plant's intercellular spaces
      of infected plants, and hence their success relies on the conditions in this
      habitat. Despite being extracellular parasites, most microbes translocate
      effectors into host cells that promote disease by acting inside cells. Initial
      studies suggested that effectors act predominantly as suppressors of plant
      immunity. These pioneering studies were trend-setting, causing a strong bias in
      the functional investigation of effectors. Yet, recent studies on bacterial model
      pathogens have identified effectors that promote disease by causing either
      increased sugar or water levels in the apoplast. These studies are likely to
      initiate a new era of effector research that will clarify the disease-promoting
      rather than defense-suppressing function of effectors, a molecular rather than
      genetic distinction.

PMID- 29597141
TI  - Preliminary evaluation of 18F-labeled LLP2A-trifluoroborate conjugates as VLA-4
      (alpha4beta1 integrin) specific radiotracers for PET imaging of melanoma.
AB  - INTRODUCTION: The transmembrane alpha4beta1 integrin receptor, or very-late
      antigen 4 (VLA-4), is associated with tumor metastasis and angiogenesis, the
      development of chemotherapeutic drug resistance, and is overexpressed in multiple
      myelomas, osteosarcomas, lymphomas, leukemias, and melanomas. The peptidomimetic,
      LLP2A, is a high-affinity ligand with specificity for the extracellular portion
      of VLA-4 and several conjugates have been evaluated in vivo by NIR-fluorescence,
      111In-SPECT and 68Ga- and 64Cu-PET imaging, but to date, not with 18F-PET.
      METHODS: Using two highly stable organotrifluoroborate prosthetic groups:
      ammoniumdimethyl-trifluoroborate (AMBF3) and a new N-pyridinyl-para
      trifluoroborate (N-Pyr-p-BF3), both capable of facile aqueous 18F-labeling by
      isotope exchange (IEX), we present the first PET imaging evaluations of two
      [18F]R-BF3--PEG2-LLP2A tracers using VLA-4 overexpressing B16-F10 murine melanoma
      tumor mouse models. RESULTS: Here, we demonstrate successful one-step 18F
      labeling of both conjugates with wet NCA [18F]F- in radiochemical yields of up to
      11.6% within 75 min at molar activities of 40-100 GBq/MUmol. Average tumor uptake
      values based on ex vivo biodistribution values were 4.4%ID/g (11) and 2.8%ID/g
      (12) using 18F-labeled LLP2A-conjugates with the two prosthetic groups: N-Pyr-p
      BF3 (5) and alkyl-N,N-dimethylammonio-BF3 (AMBF3) (7), respectively, and was
      found to be target-specific as evidenced by in vivo blocking controls. Dynamic
      PET scanning and biodistribution studies revealed slow clearance of the [18F]R
      BF3--PEG2-LLP2A tracers from the tumors, and also substantial uptake in the
      intestines, gall bladder, liver and bladder. Observed bone uptake was blockable,
      consistent with known VLA-4 expression in hematopoietic stem cells found in bone
      marrow. CONCLUSIONS: These studies show that these [18F]R-BF3--PEG2-LLP2A
      conjugates (11 and 12) are promising VLA-4 targeting radiotracers, yet, further
      optimization will be required to reduce uptake in the gastro-intestinal tract.

PMID- 29597142
TI  - Programmable prostate palpation simulator using property-changing pneumatic
      bladder.
AB  - The currently available prostate palpation simulators are based on either a
      physical mock-up or pure virtual simulation. Both cases have their inherent
      limitations. The former lacks flexibility in presenting abnormalities and
      scenarios because of the static nature of the mock-up and has usability issues
      because the prostate model must be replaced in different scenarios. The latter
      has realism issues, particularly in haptic feedback, because of the very limited
      performance of haptic hardware and inaccurate haptic simulation. This paper
      presents a highly flexible and programmable simulator with high haptic fidelity.
      Our new approach is based on a pneumatic-driven, property-changing, silicone
      prostate mock-up that can be embedded in a human torso mannequin. The mock-up has
      seven pneumatically controlled, multi-layered bladder cells to mimic the
      stiffness, size, and location changes of nodules in the prostate. The size is
      controlled by inflating the bladder with positive pressure in the chamber, and a
      hard nodule can be generated using the particle jamming technique; the fine sand
      in the bladder becomes stiff when it is vacuumed. The programmable valves and
      system identification process enable us to precisely control the size and
      stiffness, which results in a simulator that can realistically generate many
      different diseases without replacing anything. The three most common
      abnormalities in a prostate are selected for demonstration, and multiple
      progressive stages of each abnormality are carefully designed based on medical
      data. A human perception experiment is performed by actual medical professionals
      and confirms that our simulator exhibits higher realism and usability than do the
      conventional simulators.

PMID- 29597140
TI  - Presynaptic origins of distinct modes of neurotransmitter release.
AB  - Presynaptic nerve terminals release neurotransmitter synchronously,
      asynchronously or spontaneously. During synchronous neurotransmission release is
      precisely coupled to action potentials, in contrast, asynchronous release events
      show only loose temporal coupling to presynaptic activity whereas spontaneous
      neurotransmission occurs independent of presynaptic activity. The mechanisms that
      give rise to this diversity in neurotransmitter release modes are poorly
      understood. Recent studies have described several presynaptic molecular pathways
      controlling synaptic vesicle pool segregation and recycling, which in turn may
      dictate distinct modes of neurotransmitter release. In this article, we review
      this recent work regarding neurotransmitter release modes and their relationship
      to synaptic vesicle pool dynamics as well as the molecular machinery that
      establishes synaptic vesicle pool identity.

PMID- 29597143
TI  - A hierarchical pipeline for breast boundary segmentation and calcification
      detection in mammograms.
AB  - Breast cancer is one of the most common cancer risks to women in the world.
      Amongst multiple breast imaging modalities, mammography has been widely used in
      breast cancer diagnosis and screening. Quantitative analyses including breast
      boundary segmentation and calcification localization are essential steps in a
      Computer Aided Diagnosis system based on mammography analysis. Due to uneven
      signal spatial distributions of pectoral muscle and glandular tissue, plus
      various artifacts in imaging, it is still challenging to automatically analyze
      mammogram images with high precision. In this paper, a fully automated pipeline
      of mammogram image processing is proposed, which estimates skin-air boundary
      using gradient weight map, detects pectoral-breast boundary by unsupervised pixel
      wise labeling with no pre-labeled areas needed, and finally detects
      calcifications inside the breast region with a novel texture filter. Experimental
      results on Mammogram Image Analysis Society database show that the proposed
      method performs breast boundary segmentation and calcification detection with
      high accuracy of 97.08% and 96.15% respectively, and slightly higher accuracies
      are achieved on Full-Field Digital Mammography image datasets. Calculation of
      Jaccard and Dice indexes between segmented breast regions and the ground truths
      are also included as comprehensive similarity evaluations, which could provide
      valuable support for mammogram analysis in clinic.

PMID- 29597146
TI  - Electromyography comparison of the effects of various footwear in the activity
      patterns of the peroneus longus and brevis muscles.
AB  - BACKGROUND: Peroneus longus and brevis (PLB) disorders are commonly in people
      with lateral ligamentous instability, ankle pain, lateral hindfoot pain and
      structures of the proximal compartment of the lower legs and their muscle
      activity is believed to be influenced by different footwear types. The proposal
      of this research is to evaluate the effects of five types of footwear with
      respect to the barefoot condition and analyze the activity patterns of PLB
      muscles in healthy subjects during the gait cycle. METHODS: Thirty healthy
      subjects were recruited in a laboratory in this cross-sectional research design.
      While walking, electromyography (EMG) activity was measured from PLB via surface
      electrodes in six experimental conditions: 1) barefoot, 2) minimalist, 3)
      pronated control, 4) air chamber, 5) ethyl-vinyl-acetate (EVA) and 6) boost.
      These data were obtained and compared. RESULTS: The peroneus brevis showed
      significant reductions in the peak amplitude of the five footwear types
      (minimalist, pronation control, air chamber, EVA and boost) with respect to the
      barefoot condition in the propulsion phase of the gait cycle during walking (P =
      0.034; P < 0.001; P < 0.001; P < 0.001; P = 0.006) and running (P = 0.004; P <
      0.001; P = 0.001; P < 0.001; P = 0.001), respectively. Furthermore, peroneus
      longus showed significant reductions in the peak amplitude of these five footwear
      types with respect to the barefoot condition in the propulsion phase of the gait
      cycle during running (P = 0.005; P = 0.038; P = 0.019; P = 0.025; P = 0.021).
      CONCLUSION: The EMG activity patterns of the PLB muscles may depend on the use of
      different types of sport shoes such as minimalist, pronation control, air
      chamber, EVA and boost footwear with respect the barefoot condition in different
      phases of the gait cycle during walking and running.

PMID- 29597145
TI  - Collaboration or negotiation: two ways of interacting suggest how shared thinking
      develops.
AB  - This paper contrasts two ways that shared thinking can be conceptualized: as
      negotiation, where individuals join their separate ideas, or collaboration, as
      people mutually engage together in a unified process, as an ensemble. We argue
      that these paradigms are culturally based, with the negotiation model fitting
      within an assumption system of separate entities-an assumption system we believe
      to be common in psychology and in middle-class European American society-and the
      collaboration model fitting within a holistic worldview that appears to be common
      in Indigenous-heritage communities of the Americas. We discuss cultural
      differences in children's interactions-as negotiation or collaboration-that
      suggest how these distinct paradigms develop.

PMID- 29597147
TI  - Caffeic acid phenethyl ester down-regulates claudin-2 expression at the
      transcriptional and post-translational levels and enhances chemosensitivity to
      doxorubicin in lung adenocarcinoma A549 cells.
AB  - Claudin-2 is highly expressed in human lung adenocarcinoma cells and involved in
      the promotion of proliferation. Here, we searched for a compound, which can
      decrease claudin-2 expression using lung adenocarcinoma A549 cells. In the
      screening using compounds included in royal jelly and propolis, the protein level
      of claudin-2 was dose-dependently decreased by caffeic acid phenethyl ester
      (CAPE), whereas the mRNA level and promoter activity were only decreased by 50
      MUM CAPE. These results suggest that CAPE down-regulates claudin-2 expression
      mediated by two different mechanisms. CAPE (50 MUM) decreased the level of p-NF
      kappaB, whereas it increased that of IkappaB. The CAPE-induced decrease in
      promoter activity of claudin-2 was blocked by the mutation in an NF-kappaB
      binding site. The inhibition of NF-kappaB may be involved in the decrease in mRNA
      level of claudin-2. The CAPE (10 MUM)-induced decrease in claudin-2 expression
      was inhibited by chloroquine, a lysosomal inhibitor. CAPE increased the
      expression and activity of protein phosphatase (PP) 1 and 2A. The CAPE-induced
      decrease in claudin-2 expression was blocked by cantharidin, a potent PPs
      inhibitor. The cell proliferation was suppressed by CAPE, which was partially
      rescued by ectopic expression of claudin-2. In addition, the toxicity and
      accumulation of doxorubicin in 3D spheroid cells were enhanced by CAPE, which was
      inhibited by ectopic expression of claudin-2. Taken together, CAPE down-regulates
      claudin-2 expression at the transcriptional and post-translational levels, and
      enhances sensitivity of cells to doxorubicin in 3D culture conditions. CAPE may
      be a useful adjunctive compound in the treatment of lung adenocarcinoma.

PMID- 29597144
TI  - Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and
      anticancer effect.
AB  - This review is directed to the redox-modulating properties and anticancer effect
      of vitamin K. The concept is focused on two aspects: (i) redox-cycle of vitamin K
      and its effect on the calcium homeostasis, "oncogenic" and "onco-suppressive"
      reactive oxygen species and the specific induction of oxidative stress in cancer;
      (ii) vitamin K plus C as a powerful redox-system, which forms a bypass between
      mitochondrial complexes II and III and thus prevents mitochondrial dysfunction,
      restores oxidative phosphorylation and aerobic glycolysis, modulates the redox
      state of endogenous redox-pairs, eliminates the hypoxic environment of cancer
      cells and induces cell death. The analyzed data suggest that vitamin C&K can
      sensitize cancer cells to conventional chemotherapy, which allows achievement of
      a lower effective dose of the drug and minimizing the harmful side-effects. The
      review is intended for a wide audience of readers - from students to specialists
      in the field.

PMID- 29597148
TI  - Methanol metabolism and archaeal community changes in a bioelectrochemical
      anaerobic digestion sequencing batch reactor with copper-coated graphite cathode.
AB  - In this study, the metabolism of methanol and changes in an archaeal community
      were examined in a bioelectrochemical anaerobic digestion sequencing batch
      reactor with a copper-coated graphite cathode (BEAD-SBRCu). Copper-coated
      graphite cathode produced methanol from food waste. The BEAD-SBRCu showed higher
      methanol removal and methane production than those of the anaerobic digestion
      (AD)-SBR. The methane production and pH of the BEAD-SBRCu were stable even under
      a high organic loading rate (OLR). The hydrogenotrophic methanogens increased
      from 32.2 to 60.0%, and the hydrogen-dependent methylotrophic methanogens
      increased from 19.5 to 37.7% in the bulk of BEAD-SBRCu at high OLR. Where
      methanol was directly injected as a single substrate into the BEAD-SBRCu, the
      main metabolism of methane production was hydrogenotrophic methanogenesis using
      carbon dioxide and hydrogen released by the oxidation of methanol on the anode
      through bioelectrochemical reactions.

PMID- 29597149
TI  - Influence of conductive material on the bioelectrochemical removal of organic
      matter and nitrogen from low strength wastewater.
AB  - The treatment of low strength wastewater that has the level of discharge standard
      for wastewater treatment plant was studied using an upflow bioelectrochemical
      reactor with an applied voltage of 0.6 V. The direct interspecies electron
      transfer (DIET) between electroactive bacteria was activated in the upflow
      bioelectrochemical reactor, which improved the substrate affinity of bacteria.
      The effluent qualities in COD and ammonia nitrogen was stable at less than 3.5
      mg/L and 7.46 mg/L at 1 h of hydraulic retention time, respectively. The
      conductive materials, including conductive sheets and conductive particles,
      further increased the biomass retention and the DIET by altering the abundance of
      dominant bacterial groups. The effluent qualities in COD and ammonia nitrogen was
      improved up to 1.98 mg/L and 2.65 mg/L, respectively, by the conductive sheets.
      The upflow bioelectrochemical reactor with conductive materials is a good
      tertiary treatment process for improving the quality of the final effluent
      discharged from wastewater treatment plant.

PMID- 29597150
TI  - Metagenomic insight into methanogenic reactors promoting direct interspecies
      electron transfer via granular activated carbon.
AB  - To provide insight into direct interspecies electron transfer via granular
      activated carbon (GAC), the effect of GAC supplementation on anaerobic digestion
      was evaluated. Compared to control samples, the GAC supplementation increased the
      total amount of methane production and its production rate by 31% and 72%,
      respectively. 16S rDNA sequencing analysis revealed a shift in the archaeal
      community composition; the Methanosarcina proportion decreased 17%, while the
      Methanosaeta proportion increased 5.6%. Metagenomic analyses based on shotgun
      sequencing demonstrated that the abundance of pilA and omcS genes belonging to
      Geobacter species decreased 69.4% and 29.4%, respectively. Furthermore, the
      analyses suggested a carbon dioxide reduction pathway rather than an acetate
      decarboxylation pathway for methane formation. Taken together, these results
      suggest that GAC improved methane production performance by shifting the
      microbial community and altering functional genes associated with direct
      interspecies electron transfer via conductive materials.

PMID- 29597151
TI  - Purchases of prescription drugs before an alcohol-related death: A ten-year
      follow-up study using linked routine data.
AB  - BACKGROUND: Physician's intention to prescribe drugs could potentially be used to
      improve targeting of alcohol interventions and enhanced disease management to
      patients with a high risk of severe alcohol-related harm within outpatient
      settings. METHODS: Comparison of ten-year incidence trajectories of 13.8 million
      reimbursed purchases of prescription drugs among 303,057 Finnish men and women of
      whom 7490 ultimately died due to alcohol-related causes (Alc+), 14,954 died
      without alcohol involvement (Alc-), and 280,613 survived until the end of 2007.
      RESULTS: 5-10 years before death, 88% of the persons with an Alc+ death had
      received prescription medication, and over two-thirds (69%) had at least one
      reimbursed purchase of drugs for the alimentary tract and metabolism, the
      cardiovascular system, or the nervous system. Among persons with an Alc+ death,
      the incidence rate (IR) for purchases of hypnotics, and sedatives was 1.38 times
      higher (95% confidence interval (CI):1.32,1.44) compared to those with an Alc-
      death, and 4.07 times higher (95%CI:3.92,4.22) compared to survivors; and the IR
      for purchases of anxiolytics was 1.40 times higher (95%CI:1.34,1.47) compared to
      those with an Alc- death, and 3.61 times higher (95%CI:3.48,3.78) compared to
      survivors. CONCLUSIONS: Using physician's intention to prescribe drugs affecting
      the alimentary tract and metabolism, cardiovascular system and nervous system
      could potentially be used to flag patients who might benefit from screening,
      targeted interventions or enhanced disease management. In particular, patients
      who are to be prescribed anxiolytics, hypnotics, and sedatives, and
      antidepressants may benefit from enhanced interventions targeted to problem
      drinking.

PMID- 29597152
TI  - Biogenic porous silica and silicon sourced from Mexican Giant Horsetail
      (Equisetum myriochaetum) and their application as supports for enzyme
      immobilization.
AB  - Porous silica-based materials are attractive for biomedical applications due to
      their biocompatibility and biodegradable character. In addition, inorganic
      supports such as porous silicon are being developed due to integrated circuit
      chip compatibility and tunable properties leading to a wide range of
      multidisciplinary applications. In this contribution, biosilica extracted from a
      rarely studied plant material (Equisetum Myriochaetum), its conversion to silicon
      and the potential for both materials to be used as supports for enzyme
      immobilization are investigated. E. myriochaetum was subject to conventional acid
      digestion to extract biogenic silica with a% yield remarkably higher (up to 3
      times) than for other Equisetum sp. (i.e. E. Arvense). The surface area of the
      isolated silica was ~400 m2/g, suitable for biotechnological applications.
      Biogenic silicon was obtained by magnesiothermic reduction. The materials were
      characterized by SEM-EDX, XRD, FT-IR, ICP-OES, TGA and BET analysis and did not
      contain significant levels of class 1 heavy elements (such as Pb, Cd, Hg and As).
      Two commercial peroxidases, horseradish peroxidase (HRP) and Coprinus cinereus
      peroxidase (CiP) were immobilized onto the biogenic materials using three
      different functionalization routes: (A) carbodiimide, (B) amine + glutaraldehyde
      and (C) amine + carbodiimide. Although both biogenic silica and porous silicon
      could be used as supports differences in behaviour were observed for the two
      enzymes. For HRP, loading onto biogenic silica via the glutaraldehyde
      immobilization technique (route B) was most effective. The loading of CiP showed
      a much higher peroxidase activity onto porous silicon than silica functionalized
      by the carbodiimide method (route A). From the properties of the extracted
      materials obtained from Equisetum Myriochaetum and the immobilization results
      observed, these materials appear to be promising for industrial and biomedical
      applications.

PMID- 29597153
TI  - Synthesis and interaction of sterol-uridine conjugate with DMPC liposomes studied
      by differential scanning calorimetry.
AB  - Differential scanning calorimetry (DSC) is a thermoanalytical technique which
      provides information on the interaction between drugs and models of cell
      membranes. Studies on the calorimetric behavior of hydrated phospholipids within
      liposomes are employed to shed light on the changes in the physico-chemical
      properties when interacting with drugs. In this report, new potential anti-cancer
      drugs such as uridine and uridine derivatives (acetonide and its succinate),
      3beta-5alpha,8alpha-endoperoxide-cholestan-6-en-3-ol (5,8-epidioxicholesterol)
      and conjugate (uridine acetonide-epidioxicholesterol succinate) have been
      synthesized. Steglich esterification method using coupling agents allowed to
      obtain the uridine acetonide-sterol conjugate. The study on the interaction
      between the drugs and dimiristoyl-phophatidilcholine (DMPC) liposomes has been
      conducted by the use of DSC. The analysis of the DSC curves indicated that the
      uridine and derivatives (acetonide and its succinate) present a very soft
      interaction with the DMPC liposomes, whereas the 5,8-epidioxicholesterol and the
      conjugate showed a strong effect on the thermotropic behavior. Our results
      suggested that the lipophilic character of uridine acetonide-sterol conjugate
      improves the affinity with the DMPC liposomes.

PMID- 29597154
TI  - Cationic polymeric N-halamines bind onto biofilms and inactivate adherent
      bacteria.
AB  - A series of amine-based cationic polymeric N-halamine precursors, poly(2,2,6,6
      tetramethyl-4-piperidyl methacrylate-co-trimethyl-2-methacryloxyethylammonium
      chloride)(PMPQ), were synthesized by copolymerizing 2,2,6,6-tetramethyl-4
      piperidyl methacrylate (TMPM) with trimethyl-2-methacryloxyethylammonium chloride
      (TMAC) at different molar ratios (TMPM:TMAC = 10:90,30:70,50:50,70:30, and
      90:10). After chlorine bleach treatment, the TMPM moieties in the new copolymers
      were transformed into amine-based N-halamines (Cl-PMPQ). The chemical structures
      of the samples were characterized with 1H NMR, FT-IR, and UV spectra, and the
      molecular weights were determined by dynamic light scattering (DLS). With lower
      than 70 mol% of the original TMPM content, the resulting Cl-PMPQ copolymers were
      soluble in water, and demonstrated potent antibacterial functions against
      Escherichia coli (E. coli, a representative Gram-negative bacteria) and
      Staphylococcus epidermidis (S. epidermidis, a representative Gram-positive
      bacteria). E. coli and S. epidermidis were allowed to form biofilms on glass
      slides. Zeta potential analyses demonstrated that the Cl-PMPQ copolymers rapidly
      adsorbed onto the preexisting biofilms, and bacterial culturing studies confirmed
      that the bound Cl-PMPQ provided a total kill of the adherent bacteria in the
      biofilms. The kinetics of the Cl-PMPQ binding onto the preexisting biofilms were
      studied with UV analyses. The data fitted well to the bimodal model. The binding
      kinetic parameters of Cl-PMPQ onto the bacterial biofilms were thus determined.

PMID- 29597155
TI  - Dynamic wetting of human blood and plasma on various surfaces.
AB  - Surface fouling from coagulated blood is a major challenge in medical industry.
      However, the wetting physics and dynamics of blood on surfaces are not well
      understood nor are the quantitative influences due to surface and fluid
      properties. The present study investigates the effect of surface wetting and
      dynamics resulting for human blood and plasma, namely hemophobicity, on surfaces
      with different wettability. To examine effects of fluid properties, the wetting
      characteristics for liquids with Ohnesorge number similar to that of blood and
      plasma are also considered. Among the tested surfaces, a superhydrophobic, non
      fluorinated, nanocomposite coating based on an inexpensive spray application of a
      polymer/nanoparticle dispersion provided a very high degree of blood and plasma
      repellency. This was evidenced by advancing contact angles greater than 153
      degrees  and roll-off angles less than 18 degrees , for both fluids, and no
      evidence of a blood trail. However, air exposure during the contact angle
      measurements led to the formation of a thin gel-like protein skin on the surface
      (even though an anti-coagulant was added), which distorted the receding droplet
      curvature. This previously unreported feature did not modify the static contact
      angle but appears to have caused a significant increase in contact angle
      hysteresis.

PMID- 29597157
TI  - Nitrite ion mitigates the formation of N-nitrosodimethylamine (NDMA) during
      chloramination of ranitidine.
AB  - Ranitidine (RNT) has been an important tertiary amine precursor of N
      nitrosodimethylamine (NDMA) in chlorine-based water treatment, due to reaction
      with monochloramine (NH2Cl) with exceptionally high molar yields up to 90%. This
      study examined the effects of nitrite ions (NO2-) on the kinetics of NDMA
      formation during the chloramination of RNT under variable concentrations of
      dissolved oxygen (DO, 0.7-7.5mg/L), RNT (5-30MUM), NH2Cl (5-20mM), NO2- or NO3-
      (0-2mM) and pH (5.6-8.6). In the absence of the NO2-, the ultimate molar yield of
      NDMA after 6h of reaction was primarily influenced by [DO] and pH, while
      marginally affected by initial [RNT] and [NH2Cl]. A kinetic model, prepared in
      accordance with the reaction sequence of NDMA formation, suggested that the rate
      determining step was accelerated with increasing [NH2Cl]0, [DO], and pH. A
      Kinetic study together with ultra-performance liquid chromatography-quadrupole
      time of flight mass spectrometer (UPLC-Q-TOF MS) and gas chromatography (GC)/TOF
      MS analyses in parallel demonstrated that the nitrite ion inhibited the
      nucleophilic substitution of the terminal amine on NH2Cl, and reduced the pseudo
      steady state concentration of N-peroxyl radicals, significantly decreasing the
      ultimate yields of NDMA.

PMID- 29597156
TI  - Longitudinal development of hippocampal subregions from childhood to adulthood.
AB  - Detailed descriptions of the development of the hippocampus promise to shed light
      on the neural foundation of development of memory and other cognitive functions,
      as well as the emergence of major mental disorders. Hippocampus is a
      heterogeneous structure with a well characterized internal complexity, but
      development of its distinct subregions in humans has remained poorly described.
      We analyzed magnetic resonance imaging (MRI) data from a large longitudinal
      sample (270 participants, 678 scans) using an automated segmentation tool and
      mixed models to delineate the development of hippocampal subregion volumes from
      childhood to adulthood. We also examined sex differences in subregion volumes and
      their development, and associations between hippocampal subregions and general
      cognitive ability. Nonlinear developmental trajectories with early volume
      increases were observed for subiculum, cornu ammonis (CA) 1, molecular layer (ML)
      and fimbria. In contrast, parasubiculum, presubiculum, CA2/3, CA4 and the granule
      cell layer of the dentate gyrus (GC-DG) showed linear volume decreases. No sex
      differences were found in hippocampal subregion development. Finally, general
      cognitive ability was positively associated with CA2/3 and CA4 volumes, as well
      as with ML development. In conclusion, hippocampal subregions appear to develop
      in diversified ways across adolescence, and specific subregions may link to
      general cognitive level.

PMID- 29597158
TI  - De-coupling interannual variations of vertical dust extinction over the
      Taklimakan Desert during 2007-2016 using CALIOP.
AB  - During the springtime, mineral dust from the Taklimakan Desert (TD) is lifted up
      to high altitudes and transported long distances by the westerlies. The vertical
      distributions of Taklimakan dust are important for both long-range transport and
      climate effects. In this study, we use CALIOP Level 3 dust extinction to describe
      interannual variation of dust extinction in TD aggregated at each 1km interval (1
      2km, 2-3km, 3-4km, 4-5km and 5-6km) above mean sea level during springtime from
      2007 to 2016. 87% of dust extinction over TD is concentrated at 1-4km taking a
      major composition of dust aerosol optical depth (AOD) and only 8.1% dust AOD is
      at 4-6km. Interannual variation of seasonal and monthly dust extinction at 1-4km
      is almost as same as dust AOD (R>0.99) but different from that at 4-6km (R are
      around 0.42). Our analysis provides observational evidence from CALIOP that
      vertical dust extinction over TD has distinctively different variability below
      and above 4km altitude and this threshold divides dust transport in TD into two
      systems. Taklimakan dust aerosols are more related to dust transport at high
      altitudes (4-10km) than low altitudes (0-4km) over downwind regions. High dust
      extinction below 4km over TD is necessary but not sufficient conditions to ensure
      dust transport easterly, while high dust extinction levels at 4-6km over TD are
      both necessary and sufficient conditions; such contrast leads to the de-coupled
      interannual variability seen by CALIOP.

PMID- 29597159
TI  - Effects of increasing atmospheric CO2 on the marine phytoplankton and bacterial
      metabolism during a bloom: A coastal mesocosm study.
AB  - Increases of atmospheric CO2 concentrations due to human activity and associated
      effects on aquatic ecosystems are recognized as an environmental issue at a
      global scale. Growing attention is being paid to CO2 enrichment effects under
      multiple stresses or fluctuating environmental conditions in order to extrapolate
      from laboratory-scale experiments to natural systems. We carried out a mesocosm
      experiment in coastal water with an assemblage of three model phytoplankton
      species and their associated bacteria under the influence of elevated CO2
      concentrations. Net community production and the metabolic characteristics of the
      phytoplankton and bacteria were monitored to elucidate how these organisms
      responded to CO2 enrichment during the course of the algal bloom. We found that
      CO2 enrichment (1000MUatm) significantly enhanced gross primary production and
      the ratio of photosynthesis to chlorophyll a by approximately 38% and 39%,
      respectively, during the early stationary phase of the algal bloom. Although
      there were few effects on bulk bacterial production, a significant decrease of
      bulk bacterial respiration (up to 31%) at elevated CO2 resulted in an increase of
      bacterial growth efficiency. The implication is that an elevation of CO2
      concentrations leads to a reduction of bacterial carbon demand and enhances
      carbon transfer efficiency through the microbial loop, with a greater proportion
      of fixed carbon being allocated to bacterial biomass and less being lost as CO2.
      The contemporaneous responses of phytoplankton and bacterial metabolism to CO2
      enrichment increased net community production by about 45%, an increase that
      would have profound implications for the carbon cycle in coastal marine
      ecosystems.

PMID- 29597160
TI  - Distribution and risk assessment of banned and other current-use pesticides in
      surface and groundwaters consumed in an agricultural catchment dominated by cocoa
      crops in the Ankobra Basin, Ghana.
AB  - The existence of pesticides, such as organochlorine pesticides, parathion-ethyl,
      methamidophos which is banned globally and some current-use non-banned pesticides
      of organophosphorus and synthetic pyrethroids in freshwater sources is an
      ecological and public health concern in many countries, including Ghana. Prompted
      by this concern, the exposure levels and risk assessment of these pesticides to
      humans and non-target organisms via groundwater and surface water sources in an
      agricultural catchment dominated by cocoa crops in the Ankobra Basin, Ghana, were
      investigated. The individual concentrations of the banned pesticides in the
      surface water and groundwater samples varied from < LOD to 0.110 MUg/L and < LOD
      to 0.055 MUg/L, respectively, while the concentrations of the non-banned
      pesticides ranged from < LOD to 0.925 MUg/L and < LOD to 2 MUg/L, respectively.
      The mean concentrations of chlorpyrifos, cypermethrin, p,p'-DDT and pirimiphos
      methyl in some water sources exceeded the EU limit of 0.1 MUg/L. Some surface
      water sources were more contaminated with DDTs, endrin, dieldrin, methoxychlor,
      chlorpyrifos, and HCH isomers than were freshwater sources in river basins in
      some countries of the world. Chlorpyrifos, p,p'-DDT and methoxychlor were
      ubiquitous in both water sources. The hydrochemical and compositional profiles of
      the pesticides indicate that water-exchange and secondary porosities in the
      bedrock likely contributed to the occurrence of the pesticides in the water
      sources. The pesticides were of low risk to humans that consume the water, but
      considering the US EPA safe limit for carcinogenic effects of 10-6, the high
      levels of DDTs, beta-HCH, and dieldrin in some of the surface water and
      groundwater sources may cause cancer in children or infants. The toxicity of
      pesticide mixtures to surface water non-target organisms decreased in the order
      of fish > Daphnia magna > algae. The pesticides in the water sources were
      anthropogenic in origin and recently used. DDT and HCH in the water were of
      technical-grade origin.

PMID- 29597161
TI  - Ammonia oxidizers and nitrite-oxidizing bacteria respond differently to long-term
      manure application in four paddy soils of south of China.
AB  - Nitrification plays an important role in the soil nitrogen (N) cycle, and
      fertilizer application may influence soil nitrifiers' abundance and composition.
      However, the effect of long-term manure application in paddy soils on nitrifying
      populations is poorly understood. We chose four long-term manure experimental
      fields in the south of China to study how the abundance and community structure
      of nitrifiers would change in response to long-term manure application using
      quantitative PCR and Miseq sequencing analyses. Our results showed that manure
      application significantly increased ammonia oxidizing archaea (AOA) abundance at
      the ChangSha (CS) and NanChang (NC) sites, while the abundance of ammonia
      oxidizing bacteria (AOB) represented 4.8- and 12.8- fold increases at the JiaXing
      (JX) and YingTan (YT) sites, respectively. Miseq sequencing of 16S rRNA genes
      indicated that manure application altered the community structure of nitrifying
      populations, especially at the NC and YT sites. The application of manure
      significantly changed AOA and nitrite oxidizing bacteria (NOB) community
      structures but not those of AOB, suggesting that AOA and NOB may be more
      sensitive to manures. Variation partitioning analysis (VPA) and redundancy
      analysis (RDA) indicated that soil pH, TN, NO3--N and water content were the main
      factors in shaping nitrifying communities. These findings suggest that nitrifiers
      respond diversely to manure application, and soil physiochemical properties play
      an important role in determining nitrifiers' abundance and communities with long
      term manure addition.

PMID- 29597162
TI  - Metal concentrations in traditional and herbal teas and their potential risks to
      human health.
AB  - Food and beverage consumption is an important route for human exposure to metals.
      Traditional tea (Camellia sinensis) is a widely-consumed beverage, which may
      contain toxic metals. This study determined total and infusion concentrations of
      5 metals including Al, As, Cd, Cr, and Pb in 47 traditional and herbal teas from
      13 countries and assessed their potential risks to human health. The data showed
      that herbal teas exhibited higher As (0.26mgkg-1), Cd (0.19mgkg-1) and Pb
      (2.32mgkg-1) than traditional teas. Black tea from India had high Cr at 31mgkg-1
      while white tea from China had low Cr at 0.39mgkg-1. Arsenic, Cd and Pb did not
      exceed the WHO limit for medicinal plants excluding one herbal tea with 1.1mgkg-1
      As and 26.4mgkg-1 Pb. However, Cr in 47% herbal teas and 73% traditional teas
      exceeded the Canada limit of 2mgkg-1. Metal concentrations in tea infusions were
      below the MCL for drinking water except for Al. Total Al and its infusion was
      lower in herbal teas (47-1745mgkg-1 and 0.09-3.95mgL-1) than traditional teas
      (50.3-2517mgkg-1 and 0.02-7.51mgL-1), with 0.9-22% and 4-49% of the Al being
      soluble in infusion. The Al concentrations in infusion in all black tea and 83,
      75 and 25% of the green, oolong and herbal teas exceeded the secondary MCL for
      drinking water at 0.2mgL-1. However, the weekly intake of Al from drinking tea
      (0.001-0.39 and 0.003-0.56mgkg-1 for children and adults) was lower than the
      provisional tolerable weekly intake for Al at 1.0mgkg-1. Our data showed that it
      is important to consider metal intake from tea consumptions, especially for Cr
      and Al in heavy tea drinkers.

PMID- 29597163
TI  - Impact of highway construction on land surface energy balance and local climate
      derived from LANDSAT satellite data.
AB  - Extensive construction of highways has a major impact on the landscape and its
      structure. They can also influence local climate and heat fluxes in the
      surrounding area. After the removal of vegetation due to highway construction,
      the amount of solar radiation energy used for plant evapotranspiration (latent
      heat flux) decreases, bringing about an increase in landscape surface
      temperature, changing the local climate and increasing surface run-off. In this
      study, we evaluated the impact of the D8 highway construction (Central Bohemia,
      Czech Republic) on the distribution of solar radiation energy into the various
      heat fluxes (latent, sensible and ground heat flux) and related surface
      functional parameters (surface temperature and surface wetness). The aim was to
      describe the severity of the impact and the distance from the actual highway in
      which it can be observed. LANDSAT multispectral satellite images and field
      meteorological measurements were used to calculate surface functional parameters
      and heat balance before and during the highway construction. Construction of a
      four-lane highway can influence the heat balance of the landscape surface as far
      as 90m in the perpendicular direction from the highway axis, i.e. up to 75m
      perpendicular from its edge. During a summer day, the decrease in evapotranspired
      water can reach up to 43.7m3 per highway kilometre. This means a reduced cooling
      effect, expressed as the decrease in latent heat flux, by an average of 29.7MWh
      per day per highway kilometre and its surroundings. The loss of the cooling
      ability of the land surface by evaporation can lead to a rise in surface
      temperature by as much as 7 degrees C. Thus, the results indicate the impact of
      extensive line constructions on the local climate.

PMID- 29597164
TI  - Presence and impact of Stockholm Convention POPs in gull eggs from Spanish and
      Portuguese natural and national parks.
AB  - The aim of the present work was to comparatively assess the occurrence and impact
      of persistent organic pollutants (POPs) in nine natural and national parks from
      Spain and Portugal using gull eggs (Larus michahellis and L. audouinii) as
      bioindicators of environmental contamination. Sampling was performed during the
      breeding season of 2016. Compounds studied include polychlorinated biphenyls
      (PCBs), organochlorinated pesticides (OC pesticides), perfluorooctane sulfonic
      acid (PFOS) and polybrominated diphenyl ethers (PBDEs), and were analyzed using
      mass spectrometric based techniques. The results showed a high contamination by
      PCBs in all colonies, with total levels ranging from 59 to 1278ng/g wet weight
      (ww), despite their use is not currently authorized. OC pesticides were also
      present in all colonies, with a high incidence of 4,4'-DDE in gull eggs at levels
      up to 218+/-50ng/g ww in L. michahellis and 760+/-412ng/g ww in L. audouinii from
      the Ebro Delta natural park. PBDEs and PFOS were also detected at levels up to
      91.7+/-21.3ng/g ww, which can be attributed to a more recent use. Except for
      PBDEs, the POP levels in eggs from L. audouinii were higher than in L.
      michahellis, presumably associated to the fish-based diet of the former. Finally,
      the effect of POP levels on eggshell parameters (volume, eggshell thickness and
      desiccation index) were investigated for each colony and gull species in order to
      evaluate the egg viability and, therefore, the reproduction success.

PMID- 29597165
TI  - Simulating stream response to floodplain connectivity and revegetation from reach
      to watershed scales: Implications for stream management.
AB  - Natural-infrastructures (e.g., floodplains) can offer multiple ecosystem services
      (ES), including flood-resilience and water quality improvement. In order to
      maintain these ES, state and non-profit organizations consider various stream
      interventions, including increased floodplain connectivity and revegetation.
      However, the effect of these interventions is rarely quantified. We build a
      hydraulic model to simulate the influence of above-mentioned interventions on
      stream power and water depth during 5 yr and 100 yr flood return-intervals for
      two watersheds in Vermont, USA. Simulated revegetation of floodplains increased
      water depth and decreased stream power, whereas increasing connectivity resulted
      in decline of both responses. Combination of increased connectivity and
      floodplain revegetation showed greatest reduction in stream-power suggesting that
      interventions may influence stream response in diverse ways. Across all three
      interventions, 14% and 48% of altered reaches showed increase in stream power and
      water depth over baseline, indicating that interventions may lead to undesirable
      outcomes and their apparent effectiveness can vary with the measure chosen for
      evaluation. Interventions also influenced up to 16% of unaltered reaches (i.e.,
      in which no interventions were implemented), indicating the consequences of
      interventions can spread both up and downstream. Multivariate analysis showed
      that up to 50% of variance in stream response to interventions is attributable to
      characteristics of reaches, indicating that these characteristics could mediate
      the effectiveness of interventions. This study offers a framework to evaluate the
      potential ES provided by natural infrastructure. All stream interventions involve
      tradeoffs among responses and between target and non-target areas, so careful
      evaluation is therefore needed to compare benefits and costs among interventions.
      Such assessments can lead to more effective management of stream-floodplain
      ecosystems both in Vermont and elsewhere.

PMID- 29597166
TI  - Synthesis of novel ring-contracted artemisinin dimers with potent anticancer
      activities.
AB  - Artemisinin is a potential anticancer agent with an interesting trioxane
      sesquiterpene structure. In order to improve the biological activity and
      metabolic stability of artemisinin, a series of novel ring-contracted artemisinin
      dimers were synthesized. These dimers were evaluated by MTT assay against six
      cancer cell lines. Most of the dimmers exhibited improved antiproliferative
      activities over artemisinin. Especially, compound 8b showed the most pronounced
      anti-cancer activity for PC12 cancer cells with an IC50 value of 1.56 MUM. Thus,
      PC12 cancer cells were used to further investigate the mechanism of
      antiproliferation for this series of compounds. Compound 8b arrested cell cycle
      at G1 phase and induced cell apoptosis via up-regulation of Bad, Bax, caspase-3
      and caspase-9 protein expressions while inhibiting the expression of Bcl-xL. The
      present studies are the first to synthesize the ring-contracted artemisinin as
      dimers and show that these dimers have potent anti-tumor activities against
      several cancer cell lines.

PMID- 29597167
TI  - Engineering a novel protease-based Exendin-4 derivative for type 2 antidiabetic
      therapeutics.
AB  - To develop an effective long-acting antidiabetic agent, we designed a novel
      Exendin-4 derivative (termed LEx4) containing an albumin-binding domain (ABD), a
      protease-cleavable linker and a native Exendin-4. Here, we present the LEx4 with
      balanced glucoregulatory activity and prolonged in vivo activity. As a first
      step, the LEx4 with purity more than 99% was prepared. Microscale thermophoresis
      (MST) results demonstrated that LEx4 associates with rat and monkey serum albumin
      with high-affinity (Ka = 1.26 * 106 M-1 and 1.52 * 106 M-1, respectively). Then
      the stability test in vitro showed the enhanced antiproteolytic ability of LEx4
      in rat and human plasma compared to native Exendin-4. Oral glucose tolerance test
      (OGTT) in type 2 diabetic mice showed the glucose-lowering efficacy of LEx4 was
      clearly dosage-dependent within 25-250 nmol/kg. In addition, the protracted
      antidiabetic effects of LEx4 were further confirmed by both multiple OGTTs and
      hypoglycemic efficacies test in type 2 diabetic mice. In Sprague Dawley (SD)
      rats, LEx4 also showed 3.3-fold longer elimination half-life (t1/2) than native
      Exendin-4. Furthermore, once daily injection of LEx4 to db/db mice achieved long
      term beneficial effects on body weight, blood biochemical values, glucose
      tolerance and pancreatic tissue. We believe LEx4 has superior pharmaceutical
      potential as a therapeutic drug to against type-2 diabetes mellitus (T2DM) based
      on these results. This strategy of albumin binding is also applicable to other
      bioactive peptides for development of long-acting therapeutic drugs.

PMID- 29597168
TI  - Design and synthesis of novel pyrrolo[2,3-a]carbazoles: 7-Chloro-2-oxo-3a-(2'-oxo
      2',3'-dihydro-1'H-indol-3'-yl)-2,3,3a,4,5,10-hexahydro-pyrrolo[3,2-a]carbazole-1
      carbonitrile as an efficient anticancer agent.
AB  - Highly efficient poly functionalized pyrrolo[3,2-a]carbazoles via ring
      contraction through rearrangement and intramolecular Michael addition reaction
      using one pot multicomponent reaction (MCR) is reported for the first time. Free
      radical scavenging and anticancer activities were determined by DPPH and MTT
      assays respectively. Of these, compound 8d exhibited most potent activity against
      HCT-15 human colon cancer cell lines with an IC50 value of 9.9 MUM and low
      toxicity toward normal human red blood cells. The morphological changes were
      visualized using scanning electron microscopy (SEM) technique, intracellular ROS
      generation measured by spectrofluorometer and gene expression levels of caspase
      3, caspase-9 and Bcl-2 were determined using Semi quantitates PCR analysis for
      the target compound. Further, the structure activity relationships were also
      carried out. The results of the present study revealed that among pyrrolo[3,2
      a]carbazole compounds, 7-chloro-2-oxo-3a-(2'-oxo-2',3'-dihydro-1'H-indol-3'-yl)
      2,3,3a,4,5,10-hexahydro-pyrrolo[3,2-a]carbazole-1-carbonitrile could be exploited
      as an excellent anticancer agent against colon cancer cells.

PMID- 29597169
TI  - Synthesis and evaluation of novel coumarin-oxime ethers as potential anti
      tubercular agents: Their DNA cleavage ability and BSA interaction study.
AB  - As a contribution to the development of novel coumarin-oxime ether conjugates
      with therapeutically interesting properties, a series of coumarin-oxime ether (1a
      1j) was synthesised using SN2 reaction of bromomethyl coumarins with butane-2,3
      dione monoxime. Invitro anti-tuberculosis activityagainstMTBH37Rv strain was
      established for the coumarin-oxime ether (1a-1j). Most of the compounds exhibited
      significant activity with minimum inhibitory concentration (MIC)in the range of
      0.04-3.12 MUg mL-1. Compound (1h) was identified as a hit candidate exhibiting
      MIC of 0.04 MUg mL-1, closer to the MIC value of Isoniazid (0.02 MUg mL-1), a
      commercially available drug for the treatment of tuberculosis. Compound 1h also
      displayed a low level of toxicity in Vero cells along with a good safety profile
      in vitro. Compounds that showed potent anti-tubercular activity were also found
      to cleave DNA more efficiently and thereby exhibit nuclease activity. The most
      active compound (1h) was further studied to deduce the mode of interaction with
      model serum protein, bovine serum albumin (BSA).

PMID- 29597170
TI  - Identification of multi-target inhibitors of leukotriene and prostaglandin E2
      biosynthesis by structural tuning of the FLAP inhibitor BRP-7.
AB  - Leukotrienes (LTs) and prostaglandin (PG)E2 are enzymatically produced from
      arachidonic acid and represent highly bioactive lipid mediators with pro
      inflammatory functions. Here, we report on novel multi-target inhibitors that
      potently and dually interfere with 5-lipoxygenase-activating protein (FLAP) and
      microsomal prostaglandin E2 synthase (mPGES)-1 in LT and PGE2 biosynthesis, based
      on the previously identified selective FLAP inhibitor BRP-7 (8, IC50 = 0.31 MUM).
      C (5)-substitution of the benzimidazole ring of BRP-7 by carboxylic acid and its
      bioisosteres provided compounds, exemplified by 57 that potently suppress LT
      formation (IC50 = 0.05 MUM) by targeting FLAP along with inhibition of mPGES-1
      (IC50 = 0.42 MUM). Besides FLAP, also 5-lipoxygenase (5-LO) and LTC4 synthase
      activities were inhibited by 57, albeit with lower potency (IC50 = 0.6 and 6.2
      MUM) than FLAP. Docking studies and molecular dynamic simulations with FLAP,
      mPGES-1 and 5-LO provide valuable insights into potential binding interactions of
      the inhibitors with their targets. Together, these novel benzimidazole
      derivatives may possess potential as leads for development of effective anti
      inflammatory drugs with multi-target properties for dually inhibiting LT and PGE2
      production.

PMID- 29597171
TI  - N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity
      against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.
AB  - A multi-step procedure has been described which afforded satisfactory yields of
      N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc
      Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl
      reduction of an amide function in presence of a carbamate group. Next, these
      cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump
      inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild
      type SA1199. In parallel, their intrinsic toxicity was appreciated on human lung
      fibroblast MRC5 cells. Therefore, the cinnamamide combining both carbamate and
      indol-3-yl groups, was found to be the most active and one of the less toxic EPI
      and constituted a promising hit.

PMID- 29597173
TI  - Comment on "Photo-assisted degradation of 2, 4, 6-trichlorophenol by an advanced
      reduction process based on sulfite anion radical: Degradation, dechlorination and
      mineralization" [Chemosphere 191 (2018) 156-165].
AB  - The sulfite-mediated photoreduction (SMP) with UV-C light showed promising
      performances especially for dechlorination of chlorinated organic compounds
      (e.g., 2, 4, 6-trichlorophenol (TCP)). The investigation of SMP for TCP is
      commented and proposed in order to clarify the mechanisms involved.

PMID- 29597172
TI  - Differences in the bioaccumulation of selenium by two earthworm species
      (Pheretima guillemi and Eisenia fetida).
AB  - Information on the bioaccumulation of selenium (Se) in soil invertebrates (e.g.
      earthworms) is rather scarce. In the present study, bioaccumulation of Se in two
      eco-physiologically different earthworms, namely anecic Pheretima guillemi and
      epigeic Eisenia fetida, was determined after 28 days exposure to a successive
      doses of Se-spiked soil, specifically 0.5, 5, 50, and 200 MUg Se g-1 soil. The
      results showed that Se concentration in earthworms elevated with increasing
      exposure levels, and maximums were up to 54.6 and 83.0 MUg g-1 dry weight in
      Pheretima guillemi and Eisenia fetida, respectively, after 4 weeks exposure to
      200 MUg Se g-1 soil. Exposure to Se caused significant inhibition on earthworm
      growth, with the fresh weight loss ranging from 8.9% to 80.5%. Bioaccumulation
      factors (BAFs), empirically-derived and non-steady state, ranged from 0.12 to
      4.17 and generally declined at higher exposure levels. Moreover, BAFs of
      Pheretima guillemi were higher than those of Eisenia fetida in low-dose Se-spiked
      soils, but the opposite was true in high-dose soils, indicating there is a
      species-specific response to exposure of Se between different earthworms. Further
      research is thus needed to reveal the accumulation pattern of Se in a wider range
      of earthworm species other than Eisenia fetida, which allows a better risk
      assessment of excessive Se to soil invertebrates and higher order organisms.

PMID- 29597174
TI  - Enhanced cesium removal from real matrices by nickel-hexacyanoferrate modified
      activated carbons.
AB  - After nuclear disasters, radioactive cesium partitions to soils and surface
      water, where it decays slowly. Hexacyanoferrates (HCFs) have excellent cesium
      removal properties but their structure is typically powdery. Many carrier
      materials, such as biomass or magnetic particles, have been used to provide a
      suitable substrate for HCFs that can be used in filters. This research uses the
      sorption properties of activated carbon (AC) to incorporate Ni-HCF, resulting in
      good structural properties of the hybrid material. These HCF-modified ACs show
      drastically improved sorption properties towards Cs after one, two and three HCF
      impregnation cycles. The activated carbon from brewer's spent grain with one
      modification cycle removes more than 80% of 1 mg L-1 Cs in a sea water solution
      and more than 98% of 1 mg L-1 Cs from surface water at a low AC dosage (0.5 g L
      1). Iron and nickel leaching is studied and found to be dependent on the type of
      modified AC used and the leaching solution. Iron leaching can be problematic in
      surface and seawater, whereas nickel leaching is especially pronounced in
      seawater.

PMID- 29597175
TI  - Seasonal variation in the bacterial community composition of a large estuarine
      reservoir and response to cyanobacterial proliferation.
AB  - This study employed high-throughput sequencing (HTS) to understand the variations
      in microbial community in the largest estuary reservoir located at the Yangtze
      River for a year. Correlations between the heterotrophic bacterial and
      cyanobacterial communities in the estuarine ecosystem were also investigated.
      Significant spatial and temporal changes were observed in the microbial community
      composition at all sites. These differences were mainly reflected on the
      variations of bacterial relative abundance. The modularity analysis on the
      network indicate that bacterial community response to the variations of
      environmental factors in the form of co-occurrence/exclusion patterns. In warm
      season, Synechococcus spp. being the dominant Cyanobacteria taxa exhibited high
      relative abundance in the reservoir. Water temperature was the critical driver
      for the proliferation of Synechococcus. Moreover, heterotrophic bacteria
      belonging to Actinobacteria, Proteobacteria (alpha-, beta-, and gamma
      Proteobacteria), Bacteroidetes and Chlorobi, exhibited positive correlations with
      Synechococcus. The co-occurrence of these bacterial OTUs suggests that specific
      taxa may benefit from the proliferation of Synechococcus. In cold season,
      bacterial OTUs belonging to Actinobacteria and Bacteroidetes shown co-occurrence
      pattern with salt ions (including K+, Na+, Mg2+, Ca2+, Cl- and SO42-) inside the
      reservoir. In conclusion, further research is required to investigate the
      ecological functions of these taxa in estuarine ecosystems.

PMID- 29597176
TI  - Effect of disinfectant residual on the interaction between bacterial growth and
      assimilable organic carbon in a drinking water distribution system.
AB  - Public health is threatened by deteriorated water quality due to bacterial
      regrowth and uncontrolled growth-related problems in drinking water distribution
      systems (DWDSs). To investigate the scope of this problem, a two-year field study
      was conducted in south China. The amount of assimilable organic carbon (AOC),
      total cell concentrations (TCC), and intact cell concentrations (ICC) of water
      samples were determined by flow cytometry. The results indicated that ICC was
      significantly correlated to AOC concentration when the chlorine concentration was
      less than 0.15 mg/L, and ICC was lower at chlorine concentrations greater than
      0.15 mg/L, suggesting that free chlorine level had effect on AOC and ICC. To
      further analyze the effect of disinfectant on AOC and bacterial growth, we
      designed an orthogonal experiment with different dosages of two commonly used
      disinfectants, chlorine and chloramine. The results demonstrated that high
      concentrations of free chlorine (>0.15 mg/L) and chloramine (>0.4 mg/L) were
      associated with relatively low proportions of intact cells and cultivable
      bacteria. Compared with chlorine, chloramine tended to cause lower AOC level and
      intact cells, likely because the chlorinated disinfection byproducts (DBPs) were
      more easily absorbed by bacteria than the chloraminated DBPs. Based on the
      statistical analysis of 240 water samples, ICC was limited when AOC concentration
      was less than 135 MUg/L, while temperature and the number of small-size particles
      showed positive effects on ICC (P<0.05). We conclude that the use of chloramine
      and controlling particle numbers should be suitable strategies to limit bacterial
      regrowth.

PMID- 29597177
TI  - Potential for biomonitoring metals and metalloids using fish condition and tissue
      analysis in an agricultural and coal mining region.
AB  - Agricultural and mining activities contribute to metal inputs in freshwater
      ecosystems around the world, which can in turn bioaccumulate in biota such as
      fish. Monitoring of metals loads in biota thus provides insight into the
      concentrations of bioavailable metals within the environment. Little research has
      been conducted on the potential of Australian freshwater fish for biomonitoring
      metals. Within the Fitzroy Basin of Central Queensland, a major agricultural and
      coal mining region, three commonly-encountered fish taxa were analysed for tissue
      metal loads. Arsenic concentrations in Nematalosa erebi and Melanotaenia
      splendida splendida tissue were elevated (above Food Standards Australia and New
      Zealand (FSANZ) guidelines), with highest concentrations in N. erebi liver tissue
      (up to 5.14 MUg/g). Lead concentrations were above the FSANZ guidelines in all
      three fish taxa analysed, with highest concentrations in Hypseleotrid full-body
      tissue (up to 5.99 MUg/g). Selenium in M. s. splendida and N. erebi tissue was
      positively correlated with total selenium in water (p < 0.05; r = 0.68 and 0.87
      respectively). Environmental boron, selenium and nickel concentrations were
      positively correlated with N. erebi liver tissue metals. N. erebi hepatosomatic
      index was negatively correlated with dissolved arsenic, manganese, and total
      phosphorus (in water). The results highlight that M. s. splendida and N. erebi
      yield bioindicators which are responsive to environmental metals, and thus have
      potential for use in biomonitoring metals. The two species are also widespread
      along the east coast of Australia, there is thus a strong potential for applying
      the results to other regions within Australia.

PMID- 29597178
TI  - Viability of honeybee colonies exposed to sunflowers grown from seeds treated
      with the neonicotinoids thiamethoxam and clothianidin.
AB  - In this study, honeybee colonies were monitored in a field study conducted on
      sunflowers grown from seeds treated with the systemic neonicotinoids thiamethoxam
      or clothianidin. This field trial was carried out in different representative
      growing areas in Spain over a beekeeping season. The health and development of
      the colonies was assessed by measuring factors that have a significant influence
      on their strength and overwintering ability. The parameters assessed were: colony
      strength (adult bees), brood development, amount of pollen and honey stores and
      presence and status of the queen. The concentration of residues (clothianidin and
      thiamethoxam) in samples of beebread and in adult bees was at the level of ng.g
      1; in the ranges of 0.10-2.89 ng g-1 and 0.05-0.12 ng g-1; 0.10-0.37 ng g-1 and
      0.01-0.05 ng g-1, respectively. Multivariate models were applied to evaluate the
      interaction among factors. No significant differences were found between the
      honeybee colonies of the different treatment groups, either exposed or not to the
      neonicotinoids. The seasonal development of the colonies was affected by the
      environmental conditions which, together with the initial strength of the bee
      colonies and the characteristics of the plots, had a significant effect on the
      different variables studied.

PMID- 29597179
TI  - Investigation of applicability of Electro-Fenton method for the mineralization of
      naphthol blue black in water.
AB  - In this study, mineralization and color removal performance of electro-Fenton
      method were examined in water containing naphthol blue black (NBB), a diazo dye.
      NBB was totally converted to intermediate species in a 15-min electrolysis at 60
      mA, but complete de-colorization took 180 min. A very high oxidation rate
      constant ((3.35 +/- 0.21) x 1010 M-1s-1) was obtained for NBB, showing its high
      reactivity towards hydroxyl radicals. A very high total organic carbon (TOC)
      removal value (45.23 mg L-1) was obtained in the first 60 min of the electro
      Fenton treatment of an aqueous solution of NBB (0.25 mM) at 300 mA, indicating
      the mineralization efficiency of the electro-Fenton method. Mineralization
      current efficiency values obtained at 300 mA gradually decreased from 24.18% to
      4.47% with the electrolysis time, indicating the presence of highly parasitic
      reactions. Gas chromatography-mass spectrometry analyses revealed that the
      cleavage of azo bonds of NBB led to formation of different aromatic and aliphatic
      oxidation intermediates. Ion chromatography analysis showed that ammonium,
      nitrate and sulfate were the mineralization end-products. The concentration of
      sulfate ion reached to its quantitative value at the 4th h of electrolysis. On
      the other hand, the total concentration of ammonium and nitrate ions reached to
      only 61% of the stoichiometric amount of initial nitrogen after a 7 h
      electrolysis. Finally, it can be said that the electro-Fenton method is a
      suitable and efficient method for the removal of NBB and its intermediates from
      water.

PMID- 29597180
TI  - Leakage of soluble microbial products from biological activated carbon filtration
      in drinking water treatment plants and its influence on health risks.
AB  - The application of ozone-biological activated carbon (O3-BAC) as an advanced
      treatment method in drinking water treatment plants (DWTPs) can help to remove
      organic micropollutants and further decrease the dissolved organic carbon (DOC)
      level in finished water. With the increase attention to microbial safety of
      drinking water, a pre-positioned O3-BAC followed by a sand filter has been
      implanted into DWTP located in Shanghai, China to increase the biostability of
      effluents. The results showed that BAC had high removal efficiencies of UV254,
      DOC and disinfection by-product formation potential (DBPFP). The removal
      efficiencies between pre- and post-positioned BAC filtrations were similar. Based
      on the analyses of fluorescence excitation-emission matrix spectrophotometry
      (FEEM), the generation and leakage of soluble microbial products (SMPs) were
      found in both two BAC filtrations on account of the increased fluorescence
      intensities and fluorescence regional integration (FRI) distribution of protein
      like organics, as well as the enhanced biological index (BIX). The leakage of
      SMPs produced by metabolism of microbes during BAC process resulted in increased
      DBPFP yield and carcinogenic factor per unit of DOC (CF/DOC). Although BAC
      filtration reduced the DBPFP and CF, there still was high health risk of
      effluents for the production of SMPs. Therefore, the health risks for SMPs
      generated by BAC filtration in drinking water advanced treatment process should
      be addressed, especially with that at high temperature.

PMID- 29597181
TI  - Trans-generational effects of ivermectin exposure in dung beetles.
AB  - Ivermectin is a powerful antiparasitic drug commonly used in cattle. Ivermectin
      residues are excreted in dung, threatening non-target coprophagous fauna such as
      dung beetles. This can have severe ecological and economic consequences for dung
      degradation and soil fertility. Even though the negative effects of direct
      ivermectin exposure on dung-degrading organisms are well known, effects could
      extend across generations. Here, we tested the effects of paternal or maternal
      exposure to ivermectin on offspring in the dung beetle Euoniticellus intermedius.
      This species is a classic study subject in ecotoxicology and sexual selection
      because males have a cephalic horn that is under intense selection via male-male
      competition. After confirming a negative effect of ivermectin on the number of
      emerged beetles, we found trans-generational effects of ivermectin exposure on
      the horn size of male offspring. Surprisingly however, this trans-generational
      effect only occurred when only the father was exposed. We detected no trans
      generational effects of ivermectin exposure on offspring number, sex ratio or
      body size. Our results confirm that ivermectin not only has a strong effect on
      exposed individuals but also in their progeny. Our study opens new questions
      about the mechanisms responsible for parental effects and their long-term fitness
      consequences in contaminated habitats.

PMID- 29597182
TI  - Potential electron donor for nanoiron supported hydrogenotrophic denitrification:
      H2 gas, Fe0, ferrous oxides, Fe2+(aq), or Fe2+(ad)?
AB  - The mechanism of electron transmission in combined nanoiron-bacteria
      denitrification cannot be explained by the classic model, in which an Fe0H2
      nitrate transferring chain is proposed. In this study, we used characteristic
      techniques and electrochemical analysis to investigate the necessity of molecular
      hydrogen for the combined denitrifying system using commercial nanoiron with
      Alcaligenes eutrophus, and to analyze its potential electron donor. Based on our
      results, nitrate removal and its by-products (NO2- and NH4+) generation was not
      significantly affected by residual H2 gas, indicating that H2 was not necessary
      for hydrogenotrophic denitrification. As to the potential electron donor
      analysis, nanoscale zero-valent iron did not appear to be the electron donor due
      to its high level of toxicity (83% mortality using nanoiron versus 36% in the
      control cells). In addition, when iron oxides (Fe3O4, Fe2O3 and FeOOH on the
      nanoiron surface) and free ferrous ions [Fe2+(aq)] were present alone, they were
      not utilized by the bacteria to degrade nitrate. According to the results of
      electrochemical analysis, adsorbed ferrous iron [Fe2+(ad)] on ferric oxides might
      be the electron donor in this kind of nitrate removal.

PMID- 29597183
TI  - Quantitative measurements in single-cell analysis: towards scalability in
      microbial bioprocess development.
AB  - Single-cell analysis in microfluidic cultivation devices bears a great potential
      for the development and optimization of industrial bioprocesses. High
      parallelization allows running a large number of cultivation experiments
      simultaneously even under quick alteration of environmental conditions. For
      example, the impact of changes in media composition on cell growth during
      classical batch cultivation can be easily resolved. A missing link for the
      scalability of microfluidic experiments is, however, their complete
      characterization via conventional performance indicators such as product titer
      and productivity. While existing mass spectrometry technology is not yet
      sufficiently coupled with microfluidics, optical methods like enzymatic assays or
      fluorescence sensors are promising alternatives but require further improvement
      to generate quantitative measurements of extracellular metabolites.

PMID- 29597184
TI  - Global exponential synchronization of inertial memristive neural networks with
      time-varying delay via nonlinear controller.
AB  - The paper is concerned with the synchronization problem of inertial memristive
      neural networks with time-varying delay. First, by choosing a proper variable
      substitution, inertial memristive neural networks described by second-order
      differential equations can be transformed into first-order differential
      equations. Then, a novel controller with a linear diffusive term and
      discontinuous sign term is designed. By using the controller, the sufficient
      conditions for assuring the global exponential synchronization of the derive and
      response neural networks are derived based on Lyapunov stability theory and some
      inequality techniques. Finally, several numerical simulations are provided to
      substantiate the effectiveness of the theoretical results.

PMID- 29597185
TI  - Diazepam for outpatient treatment of nonconvulsive status epilepticus in
      pediatric patients with Angelman syndrome.
AB  - Nonconvulsive status epilepticus (NCSE) is present in multiple pediatric
      neurogenetic syndromes with epileptic encephalopathies. While intravenous (IV)
      medications are used inpatient for treatment of critical illness-related NCSE,
      there is no consensus on treatment of ambulatory NCSE. Up to 50% of patients with
      Angelman syndrome (AS) have NCSE with myoclonic or atypical absence status. Here
      we report our experience in pediatric patients with AS and NCSE treated
      outpatient with a tapering course of oral diazepam. We conducted a chart review
      of 104 patients seen in the Angelman Syndrome Clinic at Massachusetts General
      Hospital from January 2008 to March 2017, who met the criteria. Response to
      treatment was defined as cessation of NCSE symptoms with electroencephalogram
      (EEG) confirmation when possible. Twenty-one patients with NCSE were identified,
      and 13 patients (9 male) with 25 episodes of NCSE were included. Mean age at NCSE
      episode was 5years 4months (15months-12years). Six patients had one episode of
      NCSE, and 7 patients had recurrent episodes (mean: 2.7; range: 2-4). Median
      diazepam treatment was 6days (4-12days), with a mean dose of 0.32mg/kg/day
      divided over 2-3 administrations, decreased every 2days. Nine episodes required
      multiple courses; however, oral diazepam alone was ultimately successful in 80%
      (20/25) of NCSE episodes. Oral diazepam was well-tolerated with no major side
      effects. A short course of oral diazepam is well-tolerated and effective in
      patients with AS who have ambulatory NCSE. It may be considered prior to
      escalating to inpatient care in AS and possibly other epilepsy syndromes.

PMID- 29597186
TI  - Levels of Endocan, Angiopoietin-2, and Hypoxia-Inducible Factor-1a in Patients
      with Autosomal Dominant Polycystic Kidney Disease and Different Levels of Renal
      Function.
AB  - BACKGROUND: Endothelial dysfunction leading to unbalanced vasoconstriction and
      ischemia of renal parenchyma is increasingly proposed as an alternative pathway
      of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However,
      human studies investigating the evolution of such phenomena are limited. This
      study investigated the levels of emerging biomarkers of endothelial function,
      angiogenesis and hypoxia, in ADPKD patients with different renal function.
      METHODS: The study population consisted of three groups: 26 ADPKD patients with
      impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45
      70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B;
      eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of
      renal disease. Circulating levels of endocan (endothelial cell-specific molecule
      1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by
      enzyme-linked immunosorbent assay techniques. RESULTS: Patients in Group A had
      significantly higher levels of endocan (7.17 +/- 0.43 ng/mL), angiopoietin-2
      (5,595.43 +/- 3,390), and HIF-1a (163.68 +/- 37.84 pg/mL) compared to patients in
      Group B (6.86 +/- 0.59 ng/mL, p = 0.017, 3,854.41 +/- 3,014.30, p = 0.018, 136.84
      +/- 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 +/- 0.69 ng/mL, 1,069
      +/- 427.88 pg/mL, 70.20 +/- 17.49 pg/mL, p < 0.001 for all comparisons). Of note,
      patients in Group B had also higher levels of all markers compared to controls (p
      < 0.001) despite having similar renal function. In correlation analyses within
      ADPKD patients, we noted strong correlations of all studied markers with
      asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r
      = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest
      correlations with eGFR. CONCLUSIONS: This study suggests that endothelial
      dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia,
      may come early in the course of ADPKD and could be a key regulator of renal
      injury progression.

PMID- 29597187
TI  - Combination Therapy with Ruxolitinib and Hydroxyurea for the Treatment of Myeloid
      Predominant Leukocytosis in a Patient with Myelofibrosis.

PMID- 29597188
TI  - Early Fluorescence in situ Hybridization Assessment during Acute Myeloid Leukemia
      Induction Chemotherapy.

PMID- 29597189
TI  - The Spectrum of Glomerulopathies in Kashmir: A Tertiary Care Experience.
AB  - BACKGROUND: There is a paucity of data on the spectrum of renal diseases
      prevalent in the Jammu and Kashmir region. OBJECTIVES: To determine the spectrum
      of glomerulopathies in adult patients attending a tertiary care centre. METHODS:
      Two hundred and twenty-one adequate biopsies from native kidneys of adult
      patients who presented with features suggestive of glomerular diseases at Sheri
      Kashmir Institute of medical sciences Srinagar Kashmir for the last 8 years were
      studied in a retrospective manner. Light and immunofluorescence (IF) microscopy
      were performed to evaluate these biopsies after obtaining well-informed consent
      from each patient. RESULTS: Of the 221 biopsies carried out, 150 were performed
      on males and 71 on females with the mean age of 29 +/- 13.5 years. The main
      presentation was the nephrotic syndrome in 177 (80%), hypertension in 60 (27%),
      renal insufficiency in 48 (21.7%), and abnormal urinary sediment in 42 (20.3%) of
      patients. The histopathology revealed minimal change disease (MCD) in 69 (31.2%),
      membranous glomerulonephritis (MGN) in 48 (21.7%), focal segmental
      glomerulsclerosis (FSG) in 49 (18%), and mesangioproliferative glomerulonephritis
      in 16 (7.2%). Patients with atypical presentation of diabetes mellitus showed
      diabetic nephropathy in 12 (5.4%) patients. Lupus nephritis was in 5 (2.2%)
      patients. Majority of the patients with MPGN had Immunoglobulin A deposits on IF.
      While evaluating the underlying cause of MGN, only 1 patient, a 62-year-old male,
      proved to have adenocarcinoma of the stomach. In the remaining patients, no
      secondary cause could be found. Thrombotic complications seen in our study were
      deep venous thrombosis, renal vein thrombosis and middle cerebral artery
      thrombosis. CONCLUSION: MCD and MGN were the most common primary glomerular
      diseases observed in our centre.

PMID- 29597190
TI  - Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large
      Cohort.
AB  - BACKGROUND: Vitamin B12 deficiency is associated with hematological,
      neurological, and cardiovascular consequences. Epidemiologic data on these
      related illnesses indicate gender differences. METHODS: A cross-sectional study
      was designed to examine gender differences in vitamin B12 deficiency among a
      healthy population. Data from healthy individuals aged 18-65, who were provided
      with a routine medical evaluation during 2000-2014, were retrieved from the
      medical charts. Individuals with background illnesses and those who had used
      medications or nutritional supplements were excluded. Vitamin B12 deficiency was
      defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was
      adjusted for age, body mass index, estimated glomerular filtration rate,
      hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation.
      Sensitivity analyses were implemented by excluding individuals with anemia,
      hyperhomocysteinemia, or folate deficiency and by age stratification. RESULTS: In
      all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels
      were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001).
      Deficiency prevalence was greater for men (25.5%) in comparison with women
      (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted
      OR 2.26; 95% CI 1.43-3.56). CONCLUSIONS: Among the healthy population, men are
      susceptible to vitamin B12 deficiency. This can be explained by neither diet
      habits nor estrogen effects. Genetic variations are therefore hypothesized to
      play a role.

PMID- 29597191
TI  - Arkadia (RING Finger Protein 111) Mediates Sumoylation-Dependent Stabilization of
      Nrf2 Through K48-Linked Ubiquitination.
AB  - BACKGROUND/AIMS: The transcription factor Nrf2 is a master regulator of the
      antioxidant defense system, protecting cells from oxidative damage. We previously
      reported that the SUMO-targeted E3 ubiquitin ligase (STUbL), RING finger protein
      4 (RNF4) accelerated the degradation rate of Nrf2 in promyelocytic leukemia
      nuclear body (PML-NB)-enriched fractions and decreased Nrf2-mediated gene
      transcription. The mechanisms that regulate Nrf2 nuclear levels are poorly
      understood. In this study, we aim to explore the role of the second mammalian
      STUbL, Arkadia/RNF111 on Nrf2. METHODS: Arkadia mediated ubiquitination was
      detected using co-immunoprecipitation assays in which whole cell lysates were
      immunoprecipated with anti-Nrf2 antibody and Western blotted with anti
      hemagglutinin (HA) antibody or anti-Lys-48 ubiquitin-specific antibody. The half
      life of Nrf2 was detected in whole cell lysates and promyelocytic leukemia
      nuclear body enriched fractions by cycloheximide-chase. Reporter gene assays were
      performed using the antioxidant response element (ARE)-containing promoter Heme
      oxygenase-1 (HO-1). RESULTS: We show that Arkadia/RNF111 is able to ubiquitinate
      Nrf2 resulting in the stabilization of Nrf2. This stabilization was mediated
      through Lys-48 ubiquitin chains, contrary to traditionally degradative role of
      Lys-48 ubiquitination, suggesting that Lys-48 ubiquitination of Nrf2 protects
      Nrf2 from degradation thereby allowing Nrf2-dependent gene transcription.
      CONCLUSION: Collectively, these findings highlight a novel mechanism to
      positively regulate nuclear Nrf2 levels in response to oxidative stress through
      Arkadia-mediated K48-linked ubiquitination of Nrf2.

PMID- 29597192
TI  - Transcatheter Closure of Patent Foramen Ovale versus Medical Therapy after
      Cryptogenic Stroke: A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Patent foramen ovale (PFO) with atrial septal aneurysm is suggested
      as an important potential source for cryptogenic strokes. Percutaneous PFO
      closure to reduce the recurrence of stroke compared to medical therapy has been
      intensely debated. The aim of this study is to assess whether PFO closure in
      patients with cryptogenic stroke is safe and effective compared with medical
      therapy. METHOD: A search of PubMed, Medline, and Cochrane Central Register from
      January 2000 through September 2017 for randomized controlled trails (RCT), which
      compared PFO closure to medical therapy in patients with cryptogenic stroke was
      conducted. We used the items "PFO or patent foramen ovale", "paradoxical
      embolism", "PFO closure" and "stroke". Data were pooled for the primary outcome
      measure using the random-effects model as pooled rate ratio (RR). The primary
      outcome was reduction in recurrent strokes. RESULT: Among 282 studies, 5 were
      selected. Our analysis included 3,440 patients (mean age 45 years, 55% men, mean
      follow-up 2.9 years), 1,829 in the PFO closure group and 1,611 in the medical
      therapy group. The I2 heterogeneity test was found to be 48%. A random effects
      model combining the results of the included studies demonstrated a statistically
      significant risk reduction in risk of recurrent stroke in the PFO closure group
      when compared with medical therapy (RR 0.42; 95% CI 0.20-0.91, p = 0.03).
      CONCLUSION: Pooled data from 5 large RCTs showed that PFO closure in patients
      with cryptogenic stroke is safe and effective intervention for prevention of
      stroke recurrence compared with medical therapy.

PMID- 29597193
TI  - Zika virus Pathogenesis in Infant Mice after Natural Transmission by the Bite of
      Infected Mosquitoes.
AB  - OBJECTIVES: The objective of this study was to understand natural disease
      progression in infant CD1 mice after the bite of Aedes aegypti mosquitoes
      infected by the Zika virus (ZIKV, MR-766 strain). METHODS: A. aegypti mosquitoes
      were experimentally infected with ZIKV MR-766 strain via the oral feeding route.
      Infected mosquitoes were allowed to feed on infant CD1 mice. Sick mice were
      euthanized, and their organs were collected and subjected to real-time RT-PCR,
      histo-pathology, and immunohistochemistry. RESULTS: Clinical symptoms appeared in
      mice after 4-5 days of being bitten by mosquitoes, following which they were
      euthanized. Real-time RT-PCR analysis showed the presence of viral RNA in various
      organs such as the brain, liver, kidney, spleen, lungs, and intestines of the
      mice. The brain tissue specimens showed higher viral loads as determined by
      threshold values (Ct value) in the real-time RT-PCR assay. Histopathological and
      immunohistochemistry studies also revealed the presence of the virus and
      associated lesions in the brain, indicating that ZIKV shows tropism for neuronal
      tissue. CONCLUSIONS: This study demonstrates ZIKV pathogenesis in infant CD1 mice
      and that these mice are highly susceptible to natural infection with this ZIKV
      strain.

PMID- 29597195
TI  - Coping with Iron Deficiency and Iron Deficiency Anemia in Combat Recruits.

PMID- 29597194
TI  - FcgammaRIIIA Negatively Impacts Humoral Immune Responses but Not Overall Lung
      Inflammation in an Ovalbumin-Induced Allergic Asthma Mouse Model.
AB  - BACKGROUND: Fcgamma receptors (FcgammaR) play substantial immune regulatory roles
      both positively and negatively in pathophysiological processes including allergy
      and asthma. Compared with FcgammaRIIB which is classically defined as an
      inhibitory receptor, mouse FcgammaRIIIA and its functional human homologue
      FcgammaRIIA have been assumed to be activating receptors. However, evidence
      demonstrating inhibitory regulation by mouse FcgammaRIIIA has recently been
      emerging. OBJECTIVE: To dissect the contributory roles of mouse FcgammaRIIIA
      (human FcgammaRIIA) in parallel with FcgammaRIIB in an ovalbumin (OVA)-induced
      mouse model of asthma and to preliminarily assess the correlation of the
      respective FcgammaR with circulating IgE levels in human asthma patients.
      METHODS: Wild-type, FcgammaRIIB-/-, and FcgammaRIIIA-/- mice were used in an OVA
      induced asthma model followed by assessment of the allergic pathology focused on
      the lung tissues. Expression levels of FcgammaRIIB, FcgammaRIIA, and FcgammaRIIIA
      on peripheral blood mononuclear cells (PBMC) together with the circulating IgE
      levels in the serum from patients with allergic asthma were analysed. RESULTS:
      Although enhanced humoral immune responses typically represented by augmented OVA
      specific IgG and IgE levels in serum were observed in the absence of FcgammaRIIIA
      in the mouse asthma model, no overall regulation by FcgammaRIIIA, especially in
      terms of those parameters measuring lung tissue inflammation, was recorded. As
      expected, in the absence of FcgammaRIIB, augmented immune responses measured as
      serum antibody levels as well as those in various regulatory pathways in this
      mouse asthma model were observed. The expression levels of human FcgammaRIIB but
      not FcgammaRIIA were negatively correlated with serum levels of IgE in human
      asthma patients. CONCLUSION: We did not find major evidence demonstrating an
      immune inhibitory role of mouse FcgammaRIIIA in this OVA-induced mouse asthma
      model. As asthma is a complex disease and the immune regulatory responses involve
      sophisticated components and pathways, the exact roles of FcgammaRIIIA as well as
      its human functional homologue FcgammaRIIA in asthma still await further
      clarification using other mouse asthma models as well as clinical studies.

PMID- 29597196
TI  - Dermocosmetics for Use in Rosacea: Guideline of the Society for Dermopharmacy.
AB  - Rosacea is a widespread inflammatory skin disease that is chronically recurrent
      and affects predominately the central parts of the face. Affected individuals
      typically react to numerous cosmetics with redness, burning, and/or worsening of
      the complexion. Consequently, there is a high demand for dermocosmetics that do
      not provoke such reactions and are suitable for use in rosacea. The present
      guideline of the Society for Dermopharmacy describes the requirements that
      dermocosmetics for use in rosacea should meet. They include, inter alia, methods
      to prove the efficacy of and tolerance to these cosmetics, as well as the product
      documentation that the manufacturer or the distributing company should make
      available to professionals, like dermatologists and pharmacists, counseling
      patients with rosacea.

PMID- 29597198
TI  - Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and
      Anxiolytic Effects in Treatment-Naive Women: A Randomized Controlled Trial.
AB  - OBJECTIVE: To conduct a randomized controlled trial to evaluate the effect of a
      12-week aerobic exercise program for migraine prevention, plasma cytokines
      concentrations (TNF-alpha, interleukin [IL]-1beta, IL-6, IL-8, IL-10, and IL
      12p70), and anxiety in women with migraine. METHODS: Women with episodic migraine
      (ICHD-II), aged between 20 and 50 years, who had never taken any prophylactic
      medication, and were physically inactive in the past 12 months were recruited
      from the university's hospital and a tertiary headache clinic between March 2012
      and March 2015. Migraine attacks were recorded in headache diaries, cytokines
      were quantified by flow cytometry, and anxiety was assessed by the 7-item General
      Anxiety Disorder (GAD-7) scale. Blood sampling and psychometric interviews were
      undertaken on headache-free days. RESULTS: Twenty participants ([mean +/- SD] age
      33.8 +/- 10.5; BMI 26 +/- 5.2) were randomly assigned and received intervention
      ("trained": n = 10) or entered on a waitlist ("inactive": n = 10). There were no
      differences between groups regarding patients' characteristics and baseline data.
      Days with migraine (p = 0.001), IL-12p70 levels (p = 0.036), and GAD-7 score (p =
      0.034) were significantly reduced in the trained group after the intervention
      period, but there were no significant changes in these variables in the inactive
      group. There was no change in the levels of the other cytokines in either group.
      There were positive correlations between a reduction in IL-12p70 level and a
      reduction in the number of days with migraine (R2 = 0.19, p = 0.045), and GAD-7
      score (R2 = 0.53, p < 0.001). CONCLUSION: The clinical and psychological
      therapeutic effects of aerobic exercise in treatment-naive women with migraine
      may involve the downregulation of IL-12p70.

PMID- 29597197
TI  - Brain Activation Patterns in Response to Conspecific and Heterospecific Social
      Acoustic Signals in Female Plainfin Midshipman Fish, Porichthys notatus.
AB  - While the peripheral auditory system of fish has been well studied, less is known
      about how the fish's brain and central auditory system process complex social
      acoustic signals. The plainfin midshipman fish, Porichthys notatus, has become a
      good species for investigating the neural basis of acoustic communication because
      the production and reception of acoustic signals is paramount for this species'
      reproductive success. Nesting males produce long-duration advertisement calls
      that females detect and localize among the noise in the intertidal zone to
      successfully find mates and spawn. How female midshipman are able to discriminate
      male advertisement calls from environmental noise and other acoustic stimuli is
      unknown. Using the immediate early gene product cFos as a marker for neural
      activity, we quantified neural activation of the ascending auditory pathway in
      female midshipman exposed to conspecific advertisement calls, heterospecific
      white seabass calls, or ambient environment noise. We hypothesized that auditory
      hindbrain nuclei would be activated by general acoustic stimuli (ambient noise
      and other biotic acoustic stimuli) whereas auditory neurons in the midbrain and
      forebrain would be selectively activated by conspecific advertisement calls. We
      show that neural activation in two regions of the auditory hindbrain, i.e., the
      rostral intermediate division of the descending octaval nucleus and the ventral
      division of the secondary octaval nucleus, did not differ via cFos immunoreactive
      (cFos-ir) activity when exposed to different acoustic stimuli. In contrast,
      female midshipman exposed to conspecific advertisement calls showed greater cFos
      ir in the nucleus centralis of the midbrain torus semicircularis compared to fish
      exposed only to ambient noise. No difference in cFos-ir was observed in the torus
      semicircularis of animals exposed to conspecific versus heterospecific calls.
      However, cFos-ir was greater in two forebrain structures that receive auditory
      input, i.e., the central posterior nucleus of the thalamus and the anterior
      tuberal hypothalamus, when exposed to conspecific calls versus either ambient
      noise or heterospecific calls. Our results suggest that higher-order neurons in
      the female midshipman midbrain torus semicircularis, thalamic central posterior
      nucleus, and hypothalamic anterior tuberal nucleus may be necessary for the
      discrimination of complex social acoustic signals. Furthermore, neurons in the
      central posterior and anterior tuberal nuclei are differentially activated by
      exposure to conspecific versus other acoustic stimuli.

PMID- 29597199
TI  - Diagnosis of Hereditary Spherocytosis and Secondary Hemochromatosis in a Patient
      with Jaundice.

PMID- 29597200
TI  - Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive
      Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of
      Cholinergic Signaling.
AB  - Hypothyroidism is a common disorder that is associated with psychological
      disturbances such as dementia, depression, and psychomotor disorders. We recently
      found that chronic treatment with the T-type calcium channel enhancer SAK3
      prevents the cholinergic neurodegeneration induced by a single intraperitoneal
      (i.p.) injection of methimazole (MMI; 75 mg/kg), thereby improving cognition.
      Here, we evaluated the acute effect of SAK3 on cognitive impairments and its
      mechanism of action following the induction of hypothyroidism. Hypothyroidism was
      induced by 2 injections of MMI (75 mg/kg, i.p.) administered once per week. Four
      weeks after the final MMI treatment, MMI-treated mice showed reduced serum
      thyroxine (T4) levels and cognitive impairments without depression-like
      behaviors. Although acute SAK3 (1.0 mg/kg, p.o.) administration failed to
      ameliorate the decreased T4 levels and histochemical destruction of the
      glomerular structure, acute SAK3 (1.0 mg/kg, p.o.) administration significantly
      reduced cognitive impairments in MMI-treated mice. Importantly, the alpha7
      nicotinic acetylcholine receptor (nAChR)-selective inhibitor methyllycaconitine
      (MLA; 12 mg/kg, i.p.) and T-type calcium channel-specific blocker NNC 55-0396 (25
      mg/kg, i.p.) antagonized the acute effect of SAK3 on memory deficits in MMI
      treated mice. We also confirmed that acute SAK3 administration does not rescue
      reduced olfactory marker protein or choline acetyltransferase immunoreactivity
      levels in the olfactory bulb or medial septum. Taken together, these results
      suggest that SAK3 has the ability to improve the cognitive decline caused by
      hypothyroidism directly through activation of nAChR signaling and T-type calcium
      channels.

PMID- 29597201
TI  - Robert Wartenberg, MD (1887-1956).
AB  - Modern technologies have, to some degree, replaced the careful elicitation of
      neurological physical signs. Many 20th century texts and monographs were devoted
      to such clinical phenomena. Foremost among them were the assiduous writings of
      Robert Wartenberg who fled Hitler to enhance Neurology in San Francisco. His work
      and influences are outlined here.

PMID- 29597202
TI  - Impact of Implementing 100% Rapid Review as a Quality Control Tool in Cervical
      Cytology.
AB  - OBJECTIVE: We aimed to evaluate the impact of implementing 100% rapid review
      (100% RR) as a quality control tool in cervical smear cytology. DESIGN: A cross
      sectional study was conducted in which cytology findings, false-negative results,
      and quality indicators were evaluated. The variables were analyzed in 2004, the
      year in which 100% RR was implemented, and again in 2013, i.e., 10 years on.
      RESULTS: Detection of atypical squamous cells of undetermined significance (ASC
      US) increased from 0.90% in 2004 to 2.47% in 2013 by routine screening. Detection
      of atypical squamous cells, cannot exclude a high-grade squamous intraepithelial
      lesion (ASC-H) increased from 13.33% in 2004 to 36.27% in 2013 by 100% RR.
      Detection of high-grade squamous intraepithelial lesion (HSIL) increased from
      0.64% in 2004 to 4.29% in 2013 by routine screening, and increased from 0% in
      2004 to 19.61% in 2013 by 100% RR. There was a significant increase (p = 0.00001)
      in the identification of false-negative results of ASC-US, low-grade squamous
      intraepithelial lesion, ASC-H, HSIL, and atypical glandular cells. All quality
      indicators had increased in 2013 when compared to 2004 results. CONCLUSIONS: Ten
      years after the implementation of the 100% RR method, improvements were found in
      the detection of atypia and precursor lesions and in quality indicators.

PMID- 29597203
TI  - Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid
      Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based
      Cytology.
AB  - OBJECTIVE: To identify cytological differences between mucosa-associated lymphoid
      tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based
      cytology (LBC). STUDY DESIGN: We observed LBC and conventional specimens from 35
      MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44
      prominent nonneoplastic lymphocytic infiltration cases. RESULTS: In MALT-L cases,
      the incidence of lymphoglandular bodies in the LBC specimens was lower than that
      in the conventional specimens (p < 0.001). Moreover, the nuclear sizes in LBC
      specimens were larger than those in conventional specimens. In 62.9% of the MALT
      L and all DLBCL specimens, large nuclei were present in > 10% of the lymphoid
      cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic
      infiltration also exhibited these findings. In LBC specimens, swollen naked
      nuclei with less punctate chromatin patterns and thin nuclear margins were
      observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic
      infiltration. Elongated nuclei were significantly more apparent in thyroid
      lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001),
      with a significantly higher incidence in LBC specimens than in conventional
      specimens (p < 0.001). CONCLUSIONS: Lymphoglandular bodies are not reliable
      markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and
      elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic
      lymphocytes in LBC specimens.

PMID- 29597204
TI  - Subjective Social Status Predicts Late-Life Memory Trajectories through Both
      Mental and Physical Health Pathways.
AB  - BACKGROUND: Subjective social status (SSS) is associated with mental and physical
      health, independent of objective socioeconomic status (SES), but its association
      with late-life cognitive decline is unknown. OBJECTIVE: This study characterizes
      the association between SSS and late-life memory trajectories in a large,
      nationally representative sample of older adults in the United States. METHODS:
      Using data from 8,530 participants aged 65 years and older in the Health and
      Retirement Study, structural equation models tested associations between SSS,
      objective SES (i.e., educational attainment, occupation, income, and wealth),
      physical and mental health, and 6-year memory trajectories, controlling for
      sociodemographic characteristics. RESULTS: Independent of objective SES, lower
      SSS was associated with worse initial memory but not subsequent memory decline.
      The association between SSS and initial memory was separately mediated by chronic
      diseases, stroke, and depressive symptoms. CONCLUSION: Results provide
      preliminary behavioral evidence for the deleterious effects of social stress on
      cognitive aging. These results may help inform the development of policies and
      interventions to reduce cognitive morbidity among older adults who perceive a low
      position on the social hierarchy.

PMID- 29597205
TI  - Prevalence of Overweight and Obesity in Hungarian Children and Adolescents.
AB  - BACKGROUND/AIMS: The prevalence of overweight and obesity in children and
      adolescents is increasing worldwide, and this condition is a risk factor for
      cardiovascular mortality. The aim of this study was to assess the prevalence of
      overweight and obesity among the 3-18-year-old population in Szolnok City and the
      surrounding areas. METHODS: Anthropometric data from healthy, white individuals
      recruited from nursery, elementary, and secondary schools were used to assess the
      prevalence of obesity and overweight in Szolnok City and the surrounding area,
      Jasz-Nagykun-Szolnok county, Hungary. Healthy subjects numbering 6,824 (54% boys)
      were included; overweight and obesity were defined according to the relevant
      guidelines. RESULTS: Overweight individuals constituted 13.4% of the population
      and 6.6% were obese. The total prevalence was higher in boys (21.6%) than in
      girls (18.1%). The peak of the prevalence was observed at age 10 in both sexes
      (boys 33%, girls 27%) followed by a gradual decrease, which was more significant
      in the case of girls. CONCLUSIONS: On the basis of the recent Hungarian data, we
      have not detected any changes in overweight and obesity in the age group 3-9
      years and we have found a significant decrease in the age group 7-14 years.
      Prevention of overweight and obesity in early childhood is essential.

PMID- 29597207
TI  - A Positive Conversion of Hormone Receptor Status Might Improve Survival after
      Liver Resection for Breast Metastases: Reply to Dr. Altundag.

PMID- 29597208
TI  - Hypoxia-Inducible Factor 1alpha (HIF-1alpha), Angiopoietin-2 (ANG-2) and Endocan:
      Novel Biomarkers of Disease Progression Involving Polycystic Kidney Disease.

PMID- 29597206
TI  - Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats.
AB  - PURPOSE: To investigate the potential protective effects of curcumin on the
      retina in diabetic rats. METHODS: An experimental diabetic rat model was induced
      by a low dose of streptozotocin combined with a high-energy diet. Rats which had
      blood glucose levels >=11.6 mmol/L were used as diabetic rats. The diabetic rats
      were randomly divided into 3 groups: diabetic rats with no treatment (DM),
      diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic
      rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally
      administered daily for 16 weeks. After 16 weeks of administration, the rats were
      euthanized, and eyes were dissected. Retinal histology was examined, and the
      thickness of the retina was measured. Ultrastructural changes of retinal ganglion
      cells, inner layer cells, retinal capillary, and membranous disks were observed
      by electron microscopy. Malondialdehyde, superoxide dismutase, and total
      antioxidant capacity were measured by ELISA. Expression levels of vascular
      endothelial growth factor (VEGF) in retina tissues were examined by
      immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in
      retina tissues were determined by immunohistochemical staining and Western
      blotting. RESULTS: Curcumin reduced the blood glucose levels of diabetic rats and
      decreased diabetes-induced body weight loss. Curcumin prevented attenuation of
      the retina in diabetic rats and ameliorated diabetes-induced ultrastructure
      changes of the retina, including thinning of the retina, apoptosis of the retinal
      ganglion cells and inner nuclear layer cells, thickening of retinal capillary
      basement membrane and disturbance of photoreceptor cell membranous disks. We also
      found that curcumin has a strong antioxidative ability in the retina of diabetic
      rats. It was observed that curcumin attenuated the expression of VEGF in the
      retina of diabetic rats. We also discovered that curcumin had an antiapoptotic
      effect by upregulating the expression of Bcl-2 and downregulating the expression
      of Bax in the retina of diabetic rats. CONCLUSIONS: Taken together, these results
      suggest that curcumin may have great therapeutic potential in the treatment of
      diabetic retinopathy which could be attributed to the hypoglycemic, antioxidant,
      VEGF-downregulating and neuroprotection properties of curcumin.

PMID- 29597209
TI  - Feasibility of "Watch-and-Wait" Management before Repeat Hepatectomy for
      Colorectal Liver Metastases.
AB  - BACKGROUND: Whether repeat hepatectomy for colorectal liver metastases should be
      performed after chemotherapy or observation is unclear. METHODS: We selected
      patients with resectable hepatic recurrence after their first hepatectomies
      performed between 2000 and 2015. They were classified according to the further
      treatment: Group A, prompt repeat hepatectomy; Group B, observation; and Group C,
      <=6 months of chemotherapy. In Group B/C, patients who later underwent
      hepatectomy and those who did not due to disease progression were classified as
      B1/C1 and B2/C2, respectively. Predictors of B2/C2 were evaluated. RESULTS:
      Groups A, B, and C consisted of 81, 36, and 17 patients, respectively. Recurrence
      free interval was longer in Group A (median months; Group A, 10.3; Group B, 5.7;
      Group C, 3.5; p < 0.01). Group B1/C1 and B2/C2 included 34 and 19 patients,
      respectively. Five-year survival after recurrence of Group B1/C1 was 56%, which
      was comparable with Group A (56%, p = 0.77) and better than Group B2/C2 (0%, p <
      0.01). Multivariate analysis showed synchronous colorectal liver metastases (OR
      7.23) and recurrent hepatic tumor number (OR 4.04) were predictors of tumor
      progression. CONCLUSION: Selecting patients optimally either for prompt or
      delayed repeat hepatectomy following chemotherapy or observation is a feasible
      strategy.

PMID- 29597210
TI  - Euodia daniellii Hemsl. (Bee-Bee Tree) Oil Attenuates Palmitate-Induced Lipid
      Accumulation and Apoptosis in Hepatocytes.
AB  - Hepatic lipid accumulation and apoptosis is elevated in patients with non
      alcoholic steatohepatitis and is closely associated with severity. Saturated
      fatty acid palmitate stimulates lipid accumulation and apoptosis in hepatocytes.
      In the present study, we examined bee-bee tree oil (BO)-mediated protective
      effects on palmitate-induced lipid accumulation and apoptosis in mouse primary
      hepatocytes. Cells were cultured in a control media or the same media containing
      150 or 300 umol/L of albumin-bound palmitate for 24 h. BO concentrations used
      were 0, 0.1, 0.2, or 0.5%. Palmitate induced lipid accumulation and mRNA
      expression of lipogenic genes such as SREBP1c and SCD1. However, BO prevented
      these changes. Furthermore, palmitate stimulated caspase-3 activity and decreased
      cell viability in the absence of BO. BO reduced palmitate-induced activation of
      caspase-3 and cell death in a dose-dependent manner. AMP-activated protein kinase
      inhibitors abolished the effects of BO. Furthermore, BO suppressed palmitate
      induced c-Jun N-terminal kinase (JNK) phosphorylation through the 5&apos;
      adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. In
      conclusion, BO attenuated palmitate-induced hepatic steatosis and apoptosis
      through AMPK-mediated suppression of JNK signaling. These data suggest that BO is
      an important determinant of saturated fatty acid-induced lipid accumulation and
      apoptosis, and may be an effective therapeutic strategy for treatment of obesity
      mediated liver diseases.

PMID- 29597211
TI  - Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in
      Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial
      Fibrillation.
AB  - BACKGROUND: We aimed to clarify associations between pre-admission risk scores
      (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic
      stroke or transient ischemic attack (TIA) patients with non-valvular atrial
      fibrillation (NVAF) using a prospective, multicenter, observational registry.
      METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with
      NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were
      defined as death/disability (modified Rankin Scale score >=3) at 2 years, 2-year
      mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of
      1,192 patients with NVAF (527 women; mean age, 78 +/- 10 years), including 1,141
      ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality,
      and ischemic or hemorrhagic events increased significantly with increasing pre
      admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for
      trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS
      BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality,
      p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point,
      1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1
      point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95%
      CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001;
      1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS
      BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p
      = 0.008; respectively) scores were independently associated with all outcome
      measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre
      admission risk scores were independently associated with death/disability at 2
      years and 2-year mortality, as well as ischemic or hemorrhagic events within 2
      years.

PMID- 29597212
TI  - Isolated Renal Hydatid Cyst Misdiagnosed and Operated as a Cystic Renal Tumor.
AB  - OBJECTIVE: The aim of this work is the presentation of a case of isolated renal
      hydatid cyst with novel findings and an unusual surgical scenario. CLINICAL
      PRESENTATION AND INTERVENTION: A 54-year-old female patient presented with left
      loin pain and a palpable left renal mass. Imaging described a well-demarcated
      left renal cystic lesion with a double-layer wall. Radical nephrectomy was
      performed due to the possibility of malignancy. On retrograde revision, the
      double-layer wall represented the detached germinative membrane of a hydatid cyst
      that was confirmed by histopathology. CONCLUSION: Isolated renal hydatid cyst
      could be misinterpreted as a renal tumor. It should be considered in the
      differential diagnosis of renal cystic lesions.

PMID- 29597213
TI  - The Staining of Mast Cells: A Historical Overview.
AB  - The specificity of several staining methods for mast cells provides the
      pathologist with a useful means for the differential diagnosis of mast cell
      tumors. Mast cells stain metachromatically with toluidine blue with greater
      intensity in cells containing smaller granules. Most stains for mast cells rely
      on the cell's content of heparin, other glycosaminoglycans, and esterase. As an
      alternative to histochemical stains, different antibodies have been used to
      identify mast cells in humans.

PMID- 29597214
TI  - Evolution of Technology for Continuous Renal Replacement Therapy: Forty Years of
      Improvement.
AB  - Continuous arteriovenous hemofiltration (CAVH) was proposed in 1977 as an
      alternative treatment for acute renal failure in patients in whom peritoneal
      dialysis or hemodialysis was clinically or technically precluded. In the mid
      1980s, this technique was extended to infants and children. CAVH presented
      important advantages in the areas of hemodynamic stability, control of
      circulating volume, and nutritional support. However, there were serious
      shortcomings such as the need for arterial cannulation and limited solute
      clearance. These problems were solved by the introduction of continuous
      arteriovenous hemodiafiltration and continuous arteriovenous hemodialysis, where
      uremic control could be achieved by increasing countercurrent dialysate flow
      rates to 1.5 or 2 L/h as necessary, or by venovenous techniques utilizing a
      double-lumen central venous catheter for vascular access. Thus, continuous
      venovenous hemofiltration replaced CAVH because of its improved performance and
      safety. From the initial adoptive technology, specific machines have been
      designed to permit safe and reliable performance of the therapy. These new
      machines have progressively undergone a series of technological steps that have
      resulted in the evolution of highly sophisticated equipment utilized today. A
      significant number of advances have taken place since the time continuous renal
      replacement therapy was initiated. In particular, there have been successful
      experiments with high-volume hemofiltration and high-permeability hemofiltration.
      The additional and combined use of sorbent has also been tested successfully.
      Progress has been made in the technology as well as the understanding of the
      pathophysiology of acute kidney injury. Today, new biomaterials and new devices
      are available and new frontiers are on the horizon. Although improvements have
      been made, a lot remains to be done. Critical care nephrology is expected to
      further evolve in the near future, especially in the area of information and
      communication technology, utilization of big data and large database registries,
      biofeedback, and assisted prescription and treatment delivery, with high
      potential for improvement in morbidity and mortality of the most severely ill
      patients.

PMID- 29597215
TI  - Evolution of Vascular Access and Anticoagulation.
AB  - Continuous renal replacement therapy (CRRT) is an important and widely used
      adjuvant treatment in critically ill patients. However, any CRRT protocol can be
      adhered to only when the technique is correctly installed and functioning
      properly. Within this context, an appropriate vascular access and a safe and
      effective circuit anticoagulation method are key requisites. The right internal
      jugular (RIJ) vein is the preferred route for insertion with the tip of the
      catheter placed in the right atrium. Both femoral veins offer a valuable
      alternative access, but catheters must be longer to avoid recirculation and
      circuit blood flow is lower as compared with that of the RIJ approach. The
      location of the catheter is not associated with differences in bacterial
      colonization/infection rate or filter/circuit lifespan. Adequate anticoagulation
      is imperative to avoid a system "shutdown" due to the early clotting of the
      filter. For a long time, unfractionated heparin (UFH) was the anticoagulant of
      choice. UFH is associated with an increased bleeding risk and requires the use of
      high circuit blood flows. The introduction of regional citrate anticoagulation
      (RCA) created a paradigm change in CRRT anticoagulation. RCA can be applied
      safely in patients with increased bleeding risk and may enhance filter and
      circuit survival as compared with UFH. RCA requires close monitoring for
      potentially serious metabolic side effects. Future perspectives include improved
      catheter technology and development of novel citrate solutions with less severe
      metabolic impact.

PMID- 29597216
TI  - Indications and Timing of Continuous Renal Replacement Therapy Application.
AB  - Renal replacement therapy (RRT) is increasingly utilized to support critically
      ill patients with severe acute kidney injury (AKI). The clinical dilemma of when
      to ideally start RRT in these patients has been a longstanding issue that is in
      need of higher quality evidence to guide clinical practice. When clinicians are
      confronted with patients with life-threatening complications of AKI, the decision
      to start RRT is straightforward. However, in the absence of clear indications,
      the ideal circumstances and timing that balance the perceived benefits and risks
      of early versus delayed RRT remain uncertain. Survey data have confirmed
      substantial practice variation in the timing of RRT initiation. Most
      observational data and small clinical trials have limitations related to
      confounding by indication, heterogeneity in case-mix and illness severity, and
      variation in defining timing thresholds for starting RRT. Recently published
      trials have further added to the clinical uncertainty. This concise review
      provides an overview of prevailing and evolving evidence on the optimal time to
      start RRT in critically ill patients with AKI.

PMID- 29597217
TI  - Prescription and Delivery of the Right Continuous Renal Replacement Therapies
      Dose.
AB  - This chapter focuses on the definitions and impact of prescription and delivery
      of the right dose of treatment in patients on continuous renal replacement
      therapy (CRRT). We define "dose" and the concepts of efficiency, intensity, and
      efficacy; differentiate their multiple components; and describe the practical
      application of those concepts to direct patient care. In the article, we
      emphasize the effects of delivered dose variation on solute control, and list the
      main factors affecting CRRT dose delivery. Finally, we summarize the main
      indicators of dose monitoring and emphasize the importance of an excellent
      quality control system to ensure appropriate delivery of care to critically ill
      patients with acute kidney injury.

PMID- 29597218
TI  - Membranes and Sorbents.
AB  - For continuous renal replacement therapy (CRRT), the extracorporeal filter
      provides solute depuration, fluid removal, and control of electrolyte and acid
      base balance in critically ill patients with acute kidney injury (AKI). The
      membranes comprising CRRT filters are almost exclusively based on hollow fiber
      designs and, while adapted from the chronic hemodialysis field, have features
      that are specific to the requirements of CRRT nevertheless. In addition, these
      devices have evolved through the 40 years of CRRT in response to changes in
      clinical practice and the desire to extend the solute removal spectrum. For some
      critically ill patients, more targeted removal of specific compounds poorly
      cleared by standard CRRT can be attempted with techniques based on adsorption.
      Sorbent hemoperfusion is now being applied more broadly in critically ill
      patients, especially in those with sepsis and systemic inflammation. In this
      review, the manner in which CRRT membranes and extracorporeal sorbents have
      evolved over the past 40 years for the treatment of critically ill patients with
      AKI and other disorders is described.

PMID- 29597219
TI  - Advances in Machine Technology.
AB  - Continuous renal replacement therapy (CRRT) machines have evolved into devices
      specifically designed for critically ill over the past 40 years. In this chapter,
      a brief history of this evolution is first provided, with emphasis on the manner
      in which changes have been made to address the specific needs of the critically
      ill patient with acute kidney injury. Subsequently, specific examples of
      technology developments for CRRT machines are discussed, including the user
      interface, pumps, pressure monitoring, safety features, and anticoagulation
      capabilities.

PMID- 29597220
TI  - Extra-Renal Indications for Continuous Renal Replacement Therapy.
AB  - Continuous renal replacement therapy (CRRT) has many potential indications that
      extend beyond the traditional removal of uremic waste products. Many of these
      stem from the capacity of CRRT to remove middle-sized molecules and its
      suitability for haemodynamically unstable patients. Using CRRT for
      immunomodulation to remove circulating plasma cytokines has created great
      enthusiasm and, in the past, immunomodulation was a frequently reported
      indication for commencing CRRT. Unfortunately, recent evidence from randomized
      controlled trials has been discouraging, and CRRT cannot be recommended for
      immunomodulation. The contemporary indications of CRRT include fluid removal in
      fluid overloaded patients with poor tolerance of volume load when other means of
      fluid removal are insufficient or have failed; removal of toxins such as ammonia
      and myoglobin, as well as acidosis management in metformin-associated lactic
      acidosis when severe acid-base disorders coexist. Other potential indications
      include removal of ingested toxins and tumour lysis syndrome in severely unstable
      critically ill patients.

PMID- 29597221
TI  - Technical Complications of Continuous Renal Replacement Therapy.
AB  - Continuous renal replacement therapy (CRRT) is commonly applied in critically ill
      patients affected by severe acute kidney injury for solute and volume control and
      to optimize acid-base and electrolytes balance. Although CRRT represents a life
      saving procedure for these patients, it is a representation of a non-physiologic
      artificial kidney and the potential benefits of the treatment could be hampered
      by clinical and technical side effects. Different parts of the CRRT system can be
      a source of technical complications. Vascular access dysfunction, activation of
      the coagulation system, air embolism, heat loss and hypothermia, fluid balance
      errors, and immune system activation are some issues the medical and nurse staff
      have to face daily in patients undergoing CRRT. A detailed understanding of these
      complications and knowledge about the technology that the staff are dealing with
      are fundamental aspects for applying CRRT safely and efficaciously.

PMID- 29597222
TI  - Clinical Complications of Continuous Renal Replacement Therapy.
AB  - The various complications of continuous renal replacement therapy (CRRT) are
      mostly preventable. Hemodynamic disturbances are dominated by hypotension due to
      the modification of volume status, myocardial dysfunction, cardiac arrhythmia, or
      modification of systemic vascular resistances, which are correlated with body
      temperature changes. Metabolic complications remain at the forefront and have
      profoundly changed with the use of regional citrate anticoagulation (RCA). RCA
      may lead to two distinct situations: citrate overload and citrate accumulation,
      respectively, responsible for metabolic alkalosis and metabolic acidosis.
      Electrolyte imbalance is also a classic occurrence with RCA. The chelation of
      cations by citrate results in hypocalcemia and hypomagnesemia in case of
      inappropriate substitution. Hemorrhagic complications have been drastically
      reduced mostly for two reasons: the use of systematic ultrasound guidance for the
      insertion of dialysis catheters and the use of RCA instead of systemic heparin
      anticoagulation. Hypothermia induced by CRRT and complications associated with
      prolonged bed rest are also better controlled today. Finally, the removal of
      undesired substances remains a major issue, especially when it comes to
      antibiotics, vitamins and micronutrients, molecules for which the intake should
      be adapted in case of CRRT.

PMID- 29597223
TI  - Discontinuation of Continuous Renal Replacement Therapy and Dialysis Dependence.
AB  - Renal replacement therapy (RRT) is a form of extracorporeal support for critical
      patients, especially for those with acute kidney injury. This therapy enables to
      gain adequate control over the great metabolic and fluids demand when kidneys are
      not able to do so; this condition is habitually present in patients who are
      admitted to intensive care units. However, it is also clear that these patients
      present a higher mortality rate and, in some cases, complications associated with
      the therapy. Therefore, it is fundamental to optimize and customize different
      aspects of RRT that range from the ideal timing including the modality and the
      dose until its suspension or ending. There currently is a great deal of
      controversy in all of these RRT-related topics. Although different predictive
      models have been proposed to determine the optimal timing of therapy
      discontinuation, nowadays urine output, serum and urine creatinine levels are
      perhaps the only variables associated with effective discontinuation. Future
      studies should focus on more accurately predicting renal recovery. This review
      provides an approach based on current evidence regarding effective
      discontinuation.

PMID- 29597224
TI  - Ensuring Quality of Care through Monitoring of Continuous Renal Replacement
      Therapies.
AB  - The continuous renal replacement therapy (CRRT) has offered life-saving treatment
      for kidney failure. Technological advances coupled with findings from clinical
      trials have allowed for refinements both in the therapy and in the way it is
      applied to patients. However, outcomes for patients requiring CRRT remain
      suboptimal. The use of information technology coupled with structured quality
      improvement programs offers a methodology for studying the delivery of CRRT with
      an eye toward improving outcomes. Furthermore, integration of information from
      the CRRT treatment can be combined with real-time data from other patient
      monitoring sources to create "feedback" loops where more timely changes in the
      CRRT prescription can occur. It is hoped that these advances may lead to further
      improvements in patient outcomes.

PMID- 29597225
TI  - Continuous Renal Replacement Therapy Quality Control and Performance Measures.
AB  - Continuous renal replacement therapy (CRRT) is one of the most predominant forms
      of renal replacement therapy (RRT) currently in use now, this therapy being the
      initial RRT modality in most critically ill patients. However, in general, the
      quality of CRRT is still suboptimal. The quality of CRRT is affected by many
      factors, including the optimal prescription and precision delivery, the CRRT
      providers' professional level, and the CRRT device used. Establishment of a
      comprehensive quality control system covering all the aspects and procedures of
      CRRT is essential. Quality measures for structure, process, and outcome of CRRT
      need to be developed, evaluated, and implemented to ensure the high quality of
      CRRT. Some CRRT quality improvement methods such as the professional education
      and specialized team and the application of citrate anticoagulation to extend
      filter lifespan have been found to be potentially beneficial but need further
      validation. After all, much work is needed in this field because of the
      heterogeneity in CRRT practice. More evidence is needed to improve the CRRT
      quality control system. These are challenges that will need to be addressed in
      the future.

PMID- 29597226
TI  - Pediatric Continuous Renal Replacement Therapy for "40 Years of Continuous Renal
      Replacement Therapy".
AB  - The provision of continuous renal replacement therapy (CRRT) to pediatric
      patients presents numerous clinical and technical challenges that have been
      addressed over the past 40 years. Children provide an informative population for
      acute kidney injury and CRRT study, as pediatric subspecialists practice with a
      preventive perspective and children often do not have the multiple severe chronic
      comorbidities that confound adult studies. In addition, the relatively small
      number of patients treated at any one pediatric center has engendered successful
      multicenter collaboration to advance the clinical and technical studies of CRRT
      provision. This chapter examines pediatric-specific issues and contributions to
      the CRRT field.

PMID- 29597227
TI  - From Continuous Renal Replacement Therapies to Multiple Organ Support Therapy.
AB  - The incidence of the multiple organ dysfunction syndrome (MODS) is rapidly
      increasing in intensive care units (ICU). It usually combines with sepsis and is
      the most frequent cause of death in the ICU patients. The nature of the ICU
      patients has changed in the last years. It includes a variety of patients with
      severe cases due to major surgical interventions, trauma, hemodynamic
      instability, sepsis, and so on but also older people than previous times. All
      these situations can easily lead to MODS. In the prior years, the only available
      and efficient therapy was renal replacement therapy (RRT) for treating acute
      renal failure, but the development of technology also gives us devices to support
      the other systems. The adequacy of any artificial organ support is evaluated by
      how closely it mimics the flexibility and efficacy of the organ systems it seeks
      to substitute or support. In a sequence of events, such as that created by sepsis
      and MODS, all these criteria should be applied at the same time but for different
      organs and different tasks. RRT and especially continuous renal replacement
      therapies (CRRT) allowed extracorporeal treatment in critically ill patients with
      hyper catabolism and fluid overload with excellent hemodynamic stability. New
      techniques in CRRT as high volume hemofiltration have been applied in septic
      patients with very promising results. In the light of these observations, a new
      thought arises: Can extracorporeal blood purification have a positive impact on
      different organ systems? A possible answer might come from the simple observation
      that all organs share one aspect in common: contact with blood. All
      extracorporeal therapies also have one aspect in common: treatment of blood.
      Based on these observations and knowledge of the molecular biology of sepsis, a
      "humoral" theory of MODS makes pathophysiological sense and its consequence
      triggers the need to consider extracorporeal therapies as multiple organ support
      therapies and not just as single organ support.

PMID- 29597229
TI  - The Symbol-Digit Modalities Test in Mild Cognitive Impairment: Evidence from
      Parkinson's Disease Patients.
AB  - BACKGROUND: The evaluation process of the performance of the symbol-digit
      modalities test (SDMT) has focused much on numerical scores paying only little
      attention to the qualitative aspects of performance. Incorporating the gaze
      analysis technique, we aimed to investigate the performance of Parkinson's
      disease (PD) patients on the written SDMT task. METHODS: Twelve patients with PD
      and normal cognition (PD-N), 11 with PD and mild cognitive impairment (PD-MCI),
      and 13 healthy participants (NC) controlled for age, sex and education were
      recruited. RESULTS: PD-MCI participants achieved significantly lower scores than
      NC and PD-N participants. Eye-movement parameters, however, did not differ among
      the study groups, and were not correlated with task performance. CONCLUSIONS:
      Impaired performance on the SDMT by PD-MCI participants despite relatively
      preserved oculomotor performance indicates that lower SDMT scores are not due -
      even in part - to visuomotor impairments otherwise seen in PD patients.

PMID- 29597228
TI  - Sexual Behaviour of the Spectral Tarsier (Tarsius spectrum) in Captivity.
AB  - Tarsius spectrum is a primate species endemic to Sulawesi. Populations of the
      species have decreased due to habitat destruction and hunting. The sexual
      behaviour of T. bancanus and T. syrichta are known, but that of T. spectrum has
      not been reported until recently. The aim of this research was to study the
      sexual behaviour of T. spectrum in captivity. We observed 3 pairs of T. spectrum
      at the captive breeding facility of the IPB Primate Research Centre for 9 months
      using focal animal sampling. We showed that principal courtship behaviours were
      scent marking (36.7%) and genital marking for females (16.2%) and genital
      inspection for males (16.0%). Copulations lasted between 3 and 4 min, starting
      with the male mounting the female and thrusting quickly as many as 168-236 times
      followed by slow thrusting 9-20 times. When slow thrusting occurred, females
      vocalized up to 6 times. At the end of the copulation sequence, males remained
      motionless with their penis inserted within the female's genitalia for about 31
      s. Copulation occurred only once for each pair during the observation period. Our
      results should be useful to support breeding programmes and conservation actions
      for tarsiers.

PMID- 29597230
TI  - Membrane-Associated Kaposi Sarcoma-Associated Herpesvirus Glycoprotein B Promotes
      Cell Adhesion and Inhibits Migration of Cells via Upregulating IL-1beta and TNF
      alpha.
AB  - OBJECTIVES: Kaposi sarcoma-associated herpesvirus (KSHV) glycoprotein B (gB) is
      expressed on the viral envelope as well as on the cytoplasmic membrane of
      infected cells. In the current study, we aimed to decipher the impact of membrane
      associated gB on adhesion and migration of cells via modulating the expression of
      cytokines. METHODS: A combination of polymerase chain reaction array, cell
      adhesion assay, and wound-healing migration assay was conducted to study the
      influence of the gB-induced cytokines on cell adhesion and migration. RESULTS:
      Membrane-associated gB was demonstrated to significantly upregulate the
      expression of IL-1beta and TNF-alpha. Elevated levels of these cytokines were
      observed in conditioned medium (CM) collected from gB-expressing cells (gB-CM)
      compared to CM collected from untransfected cells or cells transfected with empty
      vector. KSHV gB-induced IL-1beta and TNF-alpha play a role in the ability of gB
      CM to mediate cell adhesion while inhibiting migration. CONCLUSION: Our results
      provide novel evidence that demonstrates full-length gB expressed on cell
      membrane to mediate adhesion and inhibit migration of cells not only by autocrine
      mechanism mediated by RGD-based interactions [Hussein et al.: BMC Cancer 2016;
      16: 148], but also by paracrine mechanism mediated by gB-induced IL-1beta and TNF
      alpha.

PMID- 29597231
TI  - Physiology of the Calcium-Parathyroid Hormone-Vitamin D Axis.
AB  - Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium
      in the extracellular fluid (ECF) binds and activates the calcium sensing receptor
      (CaSR) on the parathyroid cells, leading to an increase in intracellular calcium.
      This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia
      leads to the opposite sequence of events, namely, lowered intracellular calcium
      and increased PTH production and secretion. PTH rapidly increases renal calcium
      reabsorption and, over hours to days, enhances osteoclastic bone resorption and
      liberates both calcium and phosphate from the skeleton. PTH also increases
      fibroblast growth factor 23 (FGF23) release from mature osteoblasts and
      osteocytes. PTH stimulates the renal conversion of 25-hydroxyvitamin D (25[OH]D)
      to 1,25(OH)2D, likely over several hours, which in turn will augment intestinal
      calcium absorption. Prolonged hypocalcemia and exposure to elevated PTH may also
      result in 1,25(OH)2D-mediated calcium and phosphorus release from bone. These
      effects restore the ECF calcium to normal and inhibit further production of PTH
      and 1,25(OH)2D. Additionally, FGF23 can be released from bone by 1,25(OH)2D and
      can in turn reduce 1,25(OH)2D concentrations. FGF23 has also been reported to
      decrease PTH production. When ECF calcium is in the hypercalcemic range, PTH
      secretion is reduced and renal 1,25(OH)2D production is decreased. In addition,
      the elevated calcium per se stimulates the renal CaSR, thus inducing calciuria.
      Therefore, suppression of PTH release and 1,25(OH)2D synthesis and stimulation of
      the renal CaSR lead to reduced renal calcium reabsorption, decreased skeletal
      calcium release, and decreased intestinal calcium absorption, resulting in the
      normalization of the elevated ECF calcium.

PMID- 29597232
TI  - Preliminaries.

PMID- 29597233
TI  - Vitamin D Assays.
AB  - The number of requests for vitamin D metabolite measurements has increased
      dramatically over the past decade leading commercial laboratories to develop
      rapid high throughput assays. The measurement of 25-hydroxyvitamin D (25[OH]D)
      and to a lesser extent 1,25-dihydroxyvitamin D (1,25[OH]2D) dominates these
      requests, but requests for multiple metabolite measurements in the same sample
      are also increasing. The most commonly used methods include immunoassays and
      liquid chromatography/mass spectrometry (LC-MS). Each method has its advantages
      and disadvantages, but with improvements in technology, especially in LC-MS, this
      method is gaining ascendance due to its greater precision and flexibility. The
      use of standards from the National Institutes of Standards and Technology has
      substantially reduced the variability from laboratory to laboratory, thereby
      improving the reliability of these measurements. Although the current demand is
      for measurement of total vitamin D metabolite levels, these metabolites circulate
      in blood tightly bound to vitamin D binding protein (DBP) and albumin with less
      than 1% free. The free concentration may be a more accurate indicator of vitamin
      D status especially in individuals with DBP levels that deviate from the normal
      population. Thus, methods to measure the free concentration at least of 25(OH)D
      are becoming available and may supplement if not replace measurements of total
      levels.

PMID- 29597234
TI  - New Concepts in Vitamin D Requirements for Children and Adolescents: A
      Controversy Revisited.
AB  - North American and European authorities have identified thresholds up to 50
      nmol/L serum 25-hydroxyvitamin D (25[OH]D) as optimal for pediatric vitamin D
      status. These recommendations are relative to skeletal endpoints, as vitamin D
      plays a pivotal role in bone mineral content (BMC) accretion. Suboptimal vitamin
      D consumption during youth may therefore hinder BMC acquisition, and contribute
      to an increased fracture risk. Though vitamin D requirements range between 400
      and 800 IU/day, not all children achieve this. To encourage adequate vitamin D
      consumption, strategies such as supplementation, food labeling, and
      fortification, are currently being investigated. There is moderate support for
      the role of vitamin D supplementation on adolescent BMC accrual; however, factors
      such as age, maturation, population ancestry, and latitude, are not consistently
      accounted for across studies. Vitamin D is also linked with extraskeletal
      endpoints (e.g., muscle mass/function, adiposity, and metabolic health) in
      children, but the cross-sectional data do not necessarily align with results from
      experimental trials. Based on the evidence currently available, there is no need
      for a revision of the pediatric vitamin D recommendations at this time.
      Additional trials are required, however, to build upon the hypothesis-generating
      observational data, and to provide evidence for future vitamin D requirements
      across the globe.

PMID- 29597235
TI  - Practical Issues in Vitamin D Replacement.
AB  - Practical clinical guidance for vitamin D assessment and management relies on a
      strong evidence base, but unfortunately there are many deficiencies in our
      current knowledge. For the general population the Institute of Medicine
      recommendations are likely to provide adequate vitamin D levels without harms.
      Thus, most adults should ingest 600-800 IU (international units) in diet and
      supplements with up to 4,000 IU daily likely to be safe. In certain populations,
      such as those with osteoporosis or after bariatric surgery, it is important to
      know the levels of circulating 25-hydroxyvitamin D, but general screening has not
      been shown to improve health. One expert group has recommended a "reasonable"
      level of 30 ng/mL in those individuals for whom testing is required.

PMID- 29597236
TI  - Extra-Skeletal Effects of Vitamin D.
AB  - There are very solid data to confirm that the vitamin D endocrine system is
      important not only for calcium transport or bone homeostasis but also for
      operational functions in most cells of the body. Preclinical studies convincingly
      demonstrated coherent actions of the vitamin D endocrine system on the
      proliferation/differentiation of most cells (and thus possibly on the evolution
      of cancer). The most plausible target tissues include skeletal and cardiac
      muscle, all immune cells, many cells involved in cardiovascular homeostasis,
      brain cells, and reproductive tissues. These data have been generated in models
      of (near) total absence of vitamin D action or when exposed to very high
      concentrations of the active hormone, 1,25-dihydroxyvitamin D or its analogs. In
      humans, observational data frequently demonstrate a link between poor vitamin D
      status and a large number of major human diseases such as cancer, muscle weakness
      and falls, infections or autoimmune diseases, hypertension and cardiovascular
      risks and events, obesity, diabetes and all aspects of the metabolic syndrome,
      and other health problems. Intervention studies so far have not convincingly
      demonstrated a positive effect on such extra-skeletal health outcomes. A very
      large number of ongoing studies (about 3,000), however, should help to clarify
      the role of vitamin D on the musculoskeletal system and on global health.

PMID- 29597237
TI  - Vitamin D and Secondary Hyperparathyroid States.
AB  - The interplay between vitamin D and parathyroid hormone (PTH) represents one of
      the most important metabolic mechanisms of regulation of the calcium/phosphorus
      homeostasis. Secondary hyperparathyroidism is therefore a major complication that
      arises as a result of reduced vitamin D levels, both as primary 25-hydroxy
      vitamin D (25[OH]D) and/or 1,25-dihydroxyvitamin D (1,25[OH]2D) reduction.
      Different metabolic pathways are involved, as well as target organs and tissues,
      with several clinical complications. The skeleton is primarily involved, but many
      other extra-skeletal organs expressing the vitamin D and/or PTH receptors may
      theoretically be affected by vitamin D inadequacy and secondary
      hyperparathyroidism. Mechanisms associated with low vitamin D (mostly, but not
      exclusively 1,25[OH]2D deficiency) and high serum PTH also intensify chronic
      kidney disease (CKD), with further consequences on the mineral metabolism system
      and development of skeletal and cardiovascular disease. Therapeutic intervention
      is primarily aimed at enhancing serum 25(OH)D levels and reducing secondary
      hyperparathyroidism, by employing different strategies and endpoints according to
      the clinical contest. This chapter reviews the current knowledge on the metabolic
      pathways involved in the vitamin D/PTH axis regulation in different clinical
      settings and gives an update on the recommended treatment strategies.

PMID- 29597238
TI  - Vitamin D and Diabetes Mellitus.
AB  - Vitamin D has been suggested as a protective compound for diabetes mellitus.
      Several mechanisms linking vitamin D to the regulation of the immune response
      support a role for vitamin D in the pathogenesis of autoimmune diabetes.
      Epidemiological evidence and observational studies suggesting that adequate
      vitamin D status is related to decreased risk of developing type 1 diabetes
      further corroborates this concept. However, only few and mostly underpowered
      randomized clinical trials have been conducted to test the effectiveness of
      vitamin D supplementation in autoimmune diabetes, with disappointing results.
      Similarly, recent evidence linking vitamin D action to insulin secretion and
      sensitivity led to the hypothesis that this compound may play a key role in the
      regulation of glucose homeostasis in both pre-diabetes and overt type 2 diabetes
      (T2D). However, the main clinical trials evaluating the efficacy of vitamin D
      supplementation for the control of glucose homeostasis in people at risk for or
      affected by T2D have yielded inconsistent results. The aim of this review is to
      summarize the rationale and results of randomized clinical trials testing vitamin
      D and its analogs in both autoimmune and T2D.

PMID- 29597239
TI  - Mammary Hibernoma: A Case Report of a Rare Disease.
AB  - Mammary hibernomas are extremely rare benign tumors composed of brown fat cells,
      with only five cases previously reported in the literature. We report the case of
      a 42-year-old female patient with a painless growing mass in her right breast. A
      partial mastectomy was performed, and the diagnosis of hibernoma was confirmed by
      the histological features and the immunohistochemical profile. Although hibernoma
      is a benign tumor, its main differential diagnoses include aggressive lesions,
      making the accurate diagnosis essential to provide adequate care to the patient.

PMID- 29597240
TI  - Maternal Asthma Is an Independent Risk Factor for Long-Term Respiratory Morbidity
      of the Offspring.
AB  - OBJECTIVE:  The objective of this study was to investigate whether maternal
      bronchial asthma increases the risk for long-term respiratory morbidity of the
      offspring. STUDY DESIGN:  A population-based cohort study compared the incidence
      of long-term pediatric hospitalizations due to respiratory disease of the
      offspring of mothers with and without bronchial asthma. Deliveries occurred
      between the years 1991 and 2014 in a tertiary medical center. Congenital
      malformations as well as multiple pregnancies were excluded. Kaplan-Meier's
      survival curve was used to estimate cumulative incidence of respiratory
      morbidity. A multivariate generalized estimating equation (GEE) logistic
      regression model analysis was used to control for confounders. RESULTS:  During
      the study period, 253,808 deliveries met the inclusion criteria; of which 1.3%
      were born to mothers with bronchial asthma (n = 3,411). During the follow-up
      period, children born to women with bronchial asthma had a significantly higher
      rate of long-term respiratory morbidity (odds ratio [OR] = 1.5; 95% confidence
      interval [CI] = 1.3-1.7; p < 0.001). Specifically, the rate of childhood asthma
      was higher among offspring of mothers with asthma (OR = 2.3; 95% CI = 1.8-2.9; p
      < 0.001). Children born to women with asthma had higher cumulative incidence of
      respiratory morbidity, using a Kaplan-Meier's survival curve (log-rank test; p <
      0.001). Using two multivariable GEE logistic regression models, controlling for
      the time to event, maternal age, and gestational age at delivery, maternal
      bronchial asthma was found to be an independent risk factor for long-term
      respiratory disease of the offspring (adjusted OR = 1.6; 95% CI = 1.4-1.9; p <
      0.001), and specifically for bronchial asthma (adjusted OR = 2.5; 95% CI = 1.9
      3.1; p < 0.001). CONCLUSION:  Maternal bronchial asthma is an independent risk
      factor for long-term respiratory morbidity of the offspring.

PMID- 29597242
TI  - Lentinoids A-D, New Natural Products Isolated from Lentinus strigellus.
AB  - Four novel lentinoids (1-4), along with the known compounds striguellone A (5),
      isopanepoxydone (6) and panepoxydone (7), were isolated as part of our studies on
      Lentinus strigellus. The structures of 1-4 have been established by 1D- and 2D
      NMR and MS analysis. Compounds (1-3) and (5-7) were tested against Listeria
      monocytogenes, Enterococcus faecalis, Pseudomonas aeruginosa and Klebsiella
      pneumoniae. These compounds showed inhibition diameters ranging from 7.5-9.5 mm,
      however, when the minimum inhibitory concentration (MIC) was determined, only
      compound 1 showed a significant activity of 200 MUg/mL. Intermediates for the
      biosynthesis of the oxygenated cyclohexenyl derivatives isolated from lentinoid
      fungi (genera Lentinus and Panus) are proposed.

PMID- 29597243
TI  - Evaluation of an Agricultural Meteorological Disaster Based on Multiple Criterion
      Decision Making and Evolutionary Algorithm.
AB  - The evaluation of a meteorological disaster can be regarded as a multiple
      criteria decision making problem because it involves many indexes. Firstly, a
      comprehensive indexing system for an agricultural meteorological disaster is
      proposed, which includes the disaster rate, the inundated rate, and the complete
      loss rate. Following this, the relative weights of the three criteria are
      acquired using a novel proposed evolutionary algorithm. The proposed algorithm
      consists of a differential evolution algorithm and an evolution strategy.
      Finally, a novel evaluation model, based on the proposed algorithm and the
      Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), is
      presented to estimate the agricultural meteorological disaster of 2008 in China.
      The geographic information system (GIS) technique is employed to depict the
      disaster. The experimental results demonstrated that the agricultural
      meteorological disaster of 2008 was very serious, especially in Hunan and Hubei
      provinces. Some useful suggestions are provided to relieve agriculture
      meteorological disasters.

PMID- 29597244
TI  - Fractionation, Bioaccessibility, and Risk Assessment of Heavy Metals in the Soil
      of an Urban Recreational Area Amended with Composted Sewage Sludge.
AB  - A composted sewage sludge (CSS) was added to the soil of an urban garden at 5%,
      10%, and 25% (w/w soil) and stabilised for 180 days. Samples were then collected
      and analysed for total heavy metal concentrations, chemical fractions, and
      bioaccessibility, together with some physicochemical properties. The results
      showed that the total chromium (Cr), copper (Cu), lead (Pb), and zinc (Zn)
      concentrations were increased with CSS addition rate. The CSS addition decreased
      the residual fractions of these four elements. The exchangeable Cr, Cu, and Pb
      fractions were very small or not detected, while Zn exhibited an increasing trend
      in its exchangeable fraction with CSS addition rate. The bioaccessibility of
      these four elements was increased with the CSS addition rate. Moreover, the Cr,
      Cu, and Zn bioaccessibility correlated positively with the total concentration,
      while the bioaccessibility of these four elements exhibited a negative
      correlation with the residual fraction. The fractionation and bioaccessibility of
      heavy metals may have also been influenced by pH, cation exchange capacity, and
      organic matter. The risk assessment code reflected the amended soil showed no or
      low environmental risks for Cr, Cu, and Pb and a medium risk for Zn. The
      hazardous index values and cancer risk levels indicated that the heavy metals in
      the soil amended with 25% CSS posed negligible potential noncarcinogenic and
      carcinogenic risks to children and adults via incidental ingestion.

PMID- 29597245
TI  - The Relevancy of paracetamol and Breastfeeding Post Infant Vaccination: A
      Systematic Review.
AB  - Background: Paracetamol may be used as an antipyretic agent for the treatment of
      fever, as well as an analgesic in the treatment of mild to moderate pain post
      vaccination in infants. The use of paracetamol during fever may be or may not be
      recommended since it may alter the natural human body immune response, although
      it may reduce pain. Objectives: The aims of this study are to describe the
      effectiveness of breastfeeding in reducing pain and paracetamol in reducing fever
      and pain post infant vaccination. Methods: Data sources and study selection was
      conducted by electronic searching of six databases. Manual reference checks of
      all articles on paracetamol and breastfeeding post infant vaccination published
      in the English language between 1978 and 2017. Two levels of screening were used
      on 9614 citations, which include screening of abstracts and titles followed by
      full text screening. The data synthesis were tabulated into study
      characteristics, quality, and effects. Results: Systematic review of
      breastfeeding included three studies from 9614 database searches found
      significant benefit from breastfeeding in pain scores and the duration of crying,
      as well as behavioural changes. None of the studies stated the detriment of
      breastfeeding before, during, and after immunization. Systematic review of
      paracetamol effectiveness included four studies from 1177 database searches found
      significant benefit from prophylaxis paracetamol in fever, one study found
      significant benefit from prophylaxis paracetamol in fussiness, and one study's
      results were found to be not significant. Two studies on evaluating the safety of
      prophylactic paracetamol in 2009 found that antibody responses to several
      antigens were significantly reduced, and the other study in 1988 found that
      antibody titres to DTP bacteria of placebo and PCM did not differ significantly.
      Conclusions: The relevancy of giving paracetamol post all types of vaccination
      may be questionable. Breastfeeding before, during, and after immunization are
      recommended for pain reduction and are proven effective. Further research is
      required in deciding if paracetamol is to be of rational use following infant
      immunization.

PMID- 29597246
TI  - Importance of Patient-Provider Communication to Adherence in Adolescents with
      Type 1 Diabetes.
AB  - Effective communication between pediatric diabetes patients and their providers
      has the potential to enhance patient satisfaction and health outcomes, as well as
      improve diabetes-related self-management. In this review, we highlight the
      importance of communication between patients and providers, focusing on the
      effect of communication on adherence in the high-risk population of adolescents
      with type 1 diabetes. We synthesize the literature describing patient-provider
      communication in pediatric populations and provide implications for practice that
      focus on the most relevant, modifiable factors for improving self-management in
      adolescents with type 1 diabetes.

PMID- 29597247
TI  - Home Hospitalization for Acute Decompensated Heart Failure: Opportunities and
      Strategies for Improved Health Outcomes.
AB  - IMPORTANCE: Heart failure (HF) is the leading cause of hospitalization among
      patients over the age of 65 in the United States and developed countries, posing
      a significant economic burden to the health care systems. More than half of the
      patients with HF will be readmitted to the hospital within 6 months from
      discharge, leading not only to increased health care related expenses but also
      functional decline, iatrogenic injuries and in-hospital infections. With the
      increasing prevalence of HF, there is a substantial need for innovative delivery
      care models that can provide hospital level of care at a patient's home.
      OBSERVATIONS: Home hospitalization was originally used to safely manage
      chronically ill patients with general medical (stroke, chronic obstructive
      pulmonary disease, deep vein thrombosis, community acquired pneumonia) and
      surgical conditions and was associated with improved patient satisfaction and
      improvement in activity of daily living status. This had no clear effect on
      readmission or cost. When hospital at home care model was applied to HF patients
      it demonstrated increased time to readmission, reduced index costs and improved
      health related quality of life, with no significant differences in adverse
      events. Eligible patients should be selected based on multiple factors taking
      into consideration applicable limitations and comorbidities. CONCLUSIONS AND
      RELEVANCE: Providing in-hospital level care to the patient's house presents a
      reliable alternative, yielding multiple benefits both for the patient, as well as
      the health care system. Formulating a well-defined model is necessary before wide
      implementation.

PMID- 29597248
TI  - N- and C-Modified TiO2 Nanotube Arrays: Enhanced Photoelectrochemical Properties
      and Effect of Nanotubes Length on Photoconversion Efficiency.
AB  - In this investigation, a new, facile, low cost and environmental-friendly method
      was introduced to fabricate N- and C-modified TiO2 nanotube arrays by immersing
      the as-anodized TiO2 nanotube arrays (TNTAs) in a urea aqueous solution with
      mechanical agitation for a short time and keeping the TNTAs immersed in the
      solution for 6 h at room temperature. Then, the TNTAs were annealed at different
      temperatures. The produced N-, C-modified TNTAs were characterized using FESEM,
      EDX, XRD, XPS, UV-Vis diffuse reflectance spectra. Modified optical properties
      with narrow band gap energy, Eg, of 2.65 eV was obtained after annealing the
      modified TNTAs at 550 &deg;C. Modified TNTAs showed enhanced photoelectochemical
      performance. Photoconversion efficiency (PCE) was increased from 4.35% for
      pristine (unmodified) TNTAs to 5.18% for modified TNTAs, an increase of 19%.
      Effect of nanotubes length of modified TNTAs on photoelectrochemical performance
      was also studied. Photocurrent density and PCE were increased by increasing
      nanotube length with a maximum PCE of 6.38% for nanotube length of 55 &micro;m.
      This high PCE value was attributed to: band gap reduction due to C- and N
      modification of TNTAs surface, increased surface area of long TNTAs compared with
      short TNTAs, investigated in previous studies.

PMID- 29597252
TI  - Exercise-Induced Muscle Damage and Oxidative Stress.
AB  - Exercise-induced muscle damage (EIMD) is associated with muscle soreness or
      discomfort and amarked decline of muscle strength during the first 12&ndash;72
      hours post-exercise [1].[...].

PMID- 29597251
TI  - "Appropriate Treatment" and Therapeutic Window in Spasticity Treatment with
      IncobotulinumtoxinA: From 100 to 1000 Units.
AB  - Many neurological diseases (ischemic and hemorrhagic stroke, multiple sclerosis,
      infant cerebral palsy, spinal cord injuries, traumatic brain injury, and other
      cerebrovascular disorders) may cause muscle spasticity. Different therapeutic
      strategies have been proposed for the treatment of spasticity. One of the major
      treatments for tone modulation is botulinum toxin type A (BTX-A), performed in
      addition to other rehabilitation strategies based on individualized
      multidisciplinary programs aimed at achieving certain goals for each patient.
      Therapeutic plans must be precisely defined as they must balance the reduction of
      spastic hypertonia and retention of residual motor function. To perform and
      optimize the treatment, an accurate clinical and instrumental evaluation of
      spasticity is needed to determine how this symptom is invalidating and to choose
      the best doses, muscles and times of injection in each patient. We introduce an
      &ldquo;appropriate treatment&rdquo; and no &ldquo;standard or high dosage
      treatment&rdquo; concept based on our retrospective observational study on 120
      patients lasting two years, according to the larger Therapeutic Index and
      Therapeutic Window of Incobotulinumtoxin A doses from 100 to 1000 units. We
      studied the efficiency and safety of this drug considering the clinical
      spasticity significance for specialist physicians and patients.

PMID- 29597250
TI  - Expression of TIM-3 on Plasmacytoid Dendritic Cells as a Predictive Biomarker of
      Decline in HIV-1 RNA Level during ART.
AB  - Depletion and functional impairment of circulating plasmacytoid dendritic cells
      (pDCs) are characteristic attributes of HIV-1-infection. The mechanism of
      dysfunction of pDCs is unclear. Here, we studied the development of phenotype of
      pDCs in a cohort of HIV-1-infected individuals monitored before the initiation
      and during a 9-month follow up with antiretroviral therapy (ART). Using
      polychromatic flow cytometry, we detected significantly higher pDC-surface
      expression of the HIV-1 receptor CD4, regulatory receptor BDCA-2, Fc&gamma;
      receptor CD32, pDC dysfunction marker TIM-3, and the marker of killer pDC, TRAIL,
      in treatment-na&iuml;ve HIV-1-infected individuals before initiation of ART when
      compared to healthy donors. After 9 months of ART, all of these markers
      approached but did not reach the expression levels observed in healthy donors. We
      found that the rate of decline in HIV-1 RNA level over the first 3 months of ART
      negatively correlated with the expression of TIM-3 on pDCs. We conclude that
      immunogenic phenotype of pDCs is not significantly restored after sustained
      suppression of HIV-1 RNA level in ART-treated patients and that the level of the
      TIM-3 expressed on pDCs in treatment na&iuml;ve patients could be a predictive
      marker of the rate of decline in the HIV-1 RNA level during ART.

PMID- 29597253
TI  - Flexible Gas Sensors Employing Octahedral Indium Oxide Films.
AB  - Indium oxide octahedral nanopowders were obtained from an ionic precursor
      compound after an oxidation process conducted under a low-oxygen atmosphere. This
      method was found to produce contamination-free indium oxide nanomaterial with
      very similar morphological and crystalline properties to the one produced by
      vapor-phase transport, but at significantly lower temperatures and higher yield.
      The as-synthesized indium oxide was mixed to an organic vehicle and microdrop
      deposited to form a film bridging the interdigitated silver electrodes patterned
      on top of a flexible, polyimide (Kapton&reg;), substrate. The gas sensing
      properties of the flexible chemoresistors towards ammonia vapors, hydrogen, and
      nitrogen dioxide were investigated. It was found that these sensors were
      remarkably sensitive to nitrogen dioxide at a low operating temperature of 150
      &deg;C. These results are consistent with the performance of vapor-phase
      transport synthesized indium oxide octahedra sensors on rigid, ceramic
      substrates. Therefore, the results presented here pave the way for the mass
      production of inexpensive gas sensors onto flexible substrates via additive
      manufacturing.

PMID- 29597249
TI  - The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas.
AB  - The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a
      variety of members including c-JUN, c-FOS and ATF, is involved in mediating many
      biological processes such as proliferation, differentiation and cell death. Since
      their discovery, the role of AP-1 TFs in cancer development has been extensively
      analysed. Multiple in vitro and in vivo studies have highlighted the complexity
      of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization
      resulting in diverse transcriptional response profiles. However, as a result of
      the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being
      recognized as promising therapeutic targets for various malignancies. In this
      review, we focus on the impact of deregulated expression of AP-1 TFs in CD30
      positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell
      Lymphoma.

PMID- 29597254
TI  - Synthesis of Controlled-Size Silica Nanoparticles from Sodium Metasilicate and
      the Effect of the Addition of PEG in the Size Distribution.
AB  - Silica nanoparticles are widely studied in emerging areas of nanomedicine because
      they are biocompatible, and their surface can be modified to provide
      functionalization. The size is intrinsically related to the performance of the
      silica nanoparticles; therefore, it is important to have control over the size.
      However, the silica nanoparticles obtained from sodium metasilicate are less
      studied than those obtained from tetraethyl orthosilicate. Moreover, the methods
      of surface modification involve several steps after the synthesis. In this work,
      the effect of different concentrations of sodium metasilicate on the size of
      silica nanoparticles was studied. In the same way, we studied the synthesis of
      organically modified silica nanoparticles in a one-step method, using
      poly(ethylene glycol). The nanoparticles were characterized by scanning electron
      microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric
      analysis. It was found that the size distribution of the silica nanoparticles
      could be modified by changing the initial concentration of sodium metasilicate.
      The one-step surface-modification method caused a significant decrease in size
      distribution.

PMID- 29597255
TI  - In Vitro Anti-Toxoplasma gondii and Antimicrobial Activity of Amides Derived from
      Cinnamic Acid.
AB  - Most cinnamic acids, their esters, amides, aldehydes, and alcohols present
      several therapeutic actions through anti-inflammatory, antitumor, and inhibitory
      activity against a great variety of microorganisms. In this work, eight amines
      derived from cinnamic acid were synthesized and tested against host cells
      infected with Toxoplasma gondii and the bacteria Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus epidermidis, and three strains of Staphylococcus
      aureus. Compounds 3 and 4 showed the best result against intracellular T. gondii,
      presenting antiparasitic activity at low concentrations (0.38 and 0.77 mM). The
      antibacterial activity of these compounds was also evaluated by the agar
      microdilution method, and amides 2 and 5 had a minimum inhibitory concentration
      of 250 ug mL-1 against two strains of S. aureus (ATCC 25923 and bovine strain LSA
      88). These also showed synergistic action along with a variety of antibiotics,
      demonstrating that amines derived from cinnamic acid have potential as
      pharmacological agents.

PMID- 29597256
TI  - Geospatial Analysis and Seasonal Distribution of West Nile Virus Vectors
      (Diptera: Culicidae) in Southern Ontario, Canada.
AB  - The purpose of this study was to establish geospatial and seasonal distributions
      of West Nile virus vectors in southern Ontario, Canada using historical
      surveillance data from 2002 to 2014. We set out to produce mosquito abundance
      prediction surfaces for each of Ontario's thirteen West Nile virus vectors. We
      also set out to determine whether elevation and proximity to conservation areas
      and provincial parks, wetlands, and population centres could be used to improve
      our model. Our results indicated that the data sets for Anopheles
      quadrimaculatus, Anopheles punctipennis, Anopheles walkeri, Culex salinarius,
      Culex tarsalis, Ochlerotatus stimulans, and Ochlerotatus triseriatus were not
      suitable for geospatial modelling because they are randomly distributed
      throughout Ontario. Spatial prediction surfaces were created for Aedes japonicus
      and proximity to wetlands, Aedes vexans and proximity to population centres,
      Culex pipiens/restuans and proximity to population centres, Ochlerotatus
      canadensis and elevation, and Ochlerotatus trivittatus and proximity to
      population centres using kriging. Seasonal distributions are presented for all
      thirteen species. We have identified both when and where vector species are most
      abundant in southern Ontario. These data have the potential to contribute to a
      more efficient and focused larvicide program and West Nile virus awareness
      campaigns.

PMID- 29597257
TI  - Evaluation of UV Curing Properties of Mixture Systems with Differently Sized
      Monomers.
AB  - Ultraviolet (UV) curing is a photopolymerization technique resulting in a three
      dimensional polymer network from monomers and oligomers after exposure to UV
      light, which is often used for fusion industry. However, shrinkage is an issue
      that needs to be resolved. Studies of single substances have been extensively
      conducted, but studies of mixture systems have not sufficiently been undertaken.
      In this study, we evaluate the shrinkage phenomenon by studying a monomer/monomer
      binary system and monomer/macromer composite systems. Shrinkage tends to increase
      when compounds varying in size are used. Similar to the shrinkage phenomenon, the
      curing rate is also relatively higher in such systems. These synergistic effects
      are evaluated to be due to the nano-porous effect, and vary with the composition
      ratio and material structure.

PMID- 29597258
TI  - Enhanced Microwave Absorption and Surface Wave Attenuation Properties of
      Co0.5Ni0.5Fe2O4 Fibers/Reduced Graphene Oxide Composites.
AB  - Co0.5Ni0.5Fe2O4 fibers with a diameter of about 270 nm and a length of about 10
      MUm were synthesized by a microemulsion-mediated solvothermal method with
      subsequent heat treatment. The Co0.5Ni0.5Fe2O4 fibers/reduced graphene oxide
      (RGO) composite was prepared by a facile in-situ chemical reduction method. The
      crystalline structures and morphologies were investigated based on X-ray
      diffraction patterns and scanning electron microscopy. Magnetization measurements
      were carried out using a vibrating sample magnetometer at room temperature.
      Co0.5Ni0.5Fe2O4 fibers/RGO composites achieve both a wider and stronger
      absorption and an adjustable surface wave attenuation compared with
      Co0.5Ni0.5Fe2O4 fibers, indicating the potential for application as advanced
      microwave absorbers.

PMID- 29597259
TI  - The Role of Circulating Free DNA and MicroRNA in Non-Invasive Diagnosis of HBV-
      and HCV-Related Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third and the fifth leading cause of cancer
      related death worldwide in men and in women, respectively. HCC generally has a
      poor prognosis, with a very low 5-year overall survival, due to delayed diagnosis
      and treatment. Early tumour detection and timely intervention are the best
      strategies to reduce morbidity and mortality in HCC patients. Histological
      evaluation of liver biopsies is the gold standard for cancer diagnosis, although
      it is an invasive, time-consuming and expensive procedure. Recently, the analysis
      of circulating free DNA (cfDNA) and RNA molecules released by tumour cells in
      body fluids, such as blood serum, saliva and urine, has attracted great interest
      for development of diagnostic assays based on circulating liver cancer molecular
      biomarkers. Such "liquid biopsies" have shown to be useful for the identification
      of specific molecular signatures in nucleic acids released by cancer cells, such
      as gene mutations and altered methylation of DNA as well as variations in the
      levels of circulating microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Body
      fluids analysis may represent a valuable strategy to monitor liver disease
      progression in subjects chronically infected with hepatitis viruses or cancer
      relapse in HCC treated patients. Several studies showed that qualitative and
      quantitative assays evaluating molecular profiles of circulating cell-free
      nucleic acids could be successfully employed for early diagnosis and therapeutic
      management of HCC patients. This review describes the state of art on the use of
      liquid biopsy for cancer driver gene mutations, deregulated DNA methylation as
      well as miRNA levels in HCC diagnosis.

PMID- 29597260
TI  - The Impact of Carnitine on Dietary Fiber and Gut Bacteria Metabolism and Their
      Mutual Interaction in Monogastrics.
AB  - Carnitine has vital roles in the endogenous metabolism of short chain fatty
      acids. It can protect and support gut microbial species, and some dietary fibers
      can reduce the available iron involved in the bioactivity of carnitine. There is
      also an antagonistic relationship between high microbial populations and
      carnitine bioavailability. This review shows the interactions between carnitine
      and gut microbial composition. It also elucidates the role of carnitine bacterial
      metabolism, mitochondrial function, fiber fermentability, and short chain fatty
      acids (SCFAs).

PMID- 29597261
TI  - Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and
      Pregnant Women: An Analysis of NHANES 2001-2014.
AB  - BACKGROUND: The 2015&ndash;2020 Dietary Guidelines for Americans (DGA) recommend
      that the general population should consume about 8 ounces (oz.) per week of a
      variety of seafood, providing approximately 250 mg per day of eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), and that pregnant and lactating women
      should consume 8&ndash;12 oz. per week of seafood. METHODS: We determined the
      usual intakes, percentage not meeting recommendations, and trends in EPA and DHA
      intakes among childbearing-age and pregnant women (15&ndash;44 years of age)
      using the NHANES cycles 2001&ndash;2002 through 2013&ndash;2014. RESULTS: For the
      childbearing-age women, the mean usual intake of seafood was 0.44 &plusmn; 0.02
      oz. equivalent per day and 100% of the population was below the DGA
      recommendation. Mean usual intakes of EPA, DHA, and combined EPA and DHA from
      foods and dietary supplements combined were 26.8 &plusmn; 1.4, 62.2 &plusmn; 1.9,
      and 88.1 &plusmn; 3.0 mg per day, respectively. Over 95% of the sample did not
      meet the daily intakes of 250 mg EPA and DHA. Similar results were observed for
      pregnant women. After controlling for covariates, there were slight but
      significant increases in EPA and DHA intakes from foods and dietary supplements
      over the 14-year span among childbearing-age (p = 0.005) and pregnant women (p =
      0.002). CONCLUSIONS: It was estimated that a majority of U.S. childbearing-age
      and pregnant women consumed significantly lower amounts of seafood than what the
      DGA recommends, which subsequently leads to low intakes of EPA and DHA; in
      addition, dietary supplement use has not eliminated the nutrient shortfall.

PMID- 29597262
TI  - Maternal Choline Supplementation during Normal Murine Pregnancy Alters the
      Placental Epigenome: Results of an Exploratory Study.
AB  - The placental epigenome regulates processes that affect placental and fetal
      development, and could be mediating some of the reported effects of maternal
      choline supplementation (MCS) on placental vascular development and nutrient
      delivery. As an extension of work previously conducted in pregnant mice, the
      current study sought to explore the effects of MCS on various epigenetic markers
      in the placenta. RNA and DNA were extracted from placentas collected on embryonic
      day 15.5 from pregnant mice fed a 1X or 4X choline diet, and were subjected to
      genome-wide sequencing procedures or mass-spectrometry-based assays to examine
      placental imprinted gene expression, DNA methylation patterns, and microRNA
      (miRNA) abundance. MCS yielded a higher (fold change = 1.63-2.25) expression of
      four imprinted genes (Ampd3, Tfpi2, Gatm and Aqp1) in the female placentas and a
      lower (fold change = 0.46-0.62) expression of three imprinted genes (Dcn, Qpct
      and Tnfrsf23) in the male placentas (false discovery rate (FDR) <= 0.05 for both
      sexes). Methylation in the promoter regions of these genes and global placental
      DNA methylation were also affected (p <= 0.05). Additionally, a lower (fold
      change = 0.3; Punadjusted = 2.05 * 10-4; FDR = 0.13) abundance of miR-2137 and a
      higher (fold change = 1.25-3.92; p < 0.05) expression of its target genes were
      detected in the 4X choline placentas. These data demonstrate that the placental
      epigenome is responsive to maternal choline intake during murine pregnancy and
      likely mediates some of the previously described choline-induced effects on
      placental and fetal outcomes.

PMID- 29597264
TI  - Image Registration-Based Bolt Loosening Detection of Steel Joints.
AB  - Self-loosening of bolts caused by repetitive loads and vibrations is one of the
      common defects that can weaken the structural integrity of bolted steel joints in
      civil structures. Many existing approaches for detecting loosening bolts are
      based on physical sensors and, hence, require extensive sensor deployment, which
      limit their abilities to cost-effectively detect loosened bolts in a large number
      of steel joints. Recently, computer vision-based structural health monitoring
      (SHM) technologies have demonstrated great potential for damage detection due to
      the benefits of being low cost, easy to deploy, and contactless. In this study,
      we propose a vision-based non-contact bolt loosening detection method that uses a
      consumer-grade digital camera. Two images of the monitored steel joint are first
      collected during different inspection periods and then aligned through two image
      registration processes. If the bolt experiences rotation between inspections, it
      will introduce differential features in the registration errors, serving as a
      good indicator for bolt loosening detection. The performance and robustness of
      this approach have been validated through a series of experimental investigations
      using three laboratory setups including a gusset plate on a cross frame, a column
      flange, and a girder web. The bolt loosening detection results are presented for
      easy interpretation such that informed decisions can be made about the detected
      loosened bolts.

PMID- 29597263
TI  - PON-tstab: Protein Variant Stability Predictor. Importance of Training Data
      Quality.
AB  - Several methods have been developed to predict effects of amino acid
      substitutions on protein stability. Benchmark datasets are essential for method
      training and testing and have numerous requirements including that the data is
      representative for the investigated phenomenon. Available machine learning
      algorithms for variant stability have all been trained with ProTherm data. We
      noticed a number of issues with the contents, quality and relevance of the
      database. There were errors, but also features that had not been clearly
      communicated. Consequently, all machine learning variant stability predictors
      have been trained on biased and incorrect data. We obtained a corrected dataset
      and trained a random forests-based tool, PON-tstab, applicable to variants in any
      organism. Our results highlight the importance of the benchmark quality,
      suitability and appropriateness. Predictions are provided for three categories:
      stability decreasing, increasing and those not affecting stability.

PMID- 29597265
TI  - Direct Printing of Stretchable Elastomers for Highly Sensitive Capillary Pressure
      Sensors.
AB  - We demonstrate the successful fabrication of highly sensitive capillary pressure
      sensors using an innovative 3D printing method. Unlike conventional capacitive
      pressure sensors where the capacitance changes were due to the pressure-induced
      interspace variations between the parallel plate electrodes, in our capillary
      sensors the capacitance was determined by the extrusion and extraction of liquid
      medium and consequent changes of dielectric constants. Significant pressure
      sensitivity advances up to 547.9 KPa-1 were achieved. Moreover, we suggest that
      our innovative capillary pressure sensors can adopt a wide range of liquid
      mediums, such as ethanol, deionized water, and their mixtures. The devices also
      showed stable performances upon repeated pressing cycles. The direct and
      versatile printing method combined with the significant performance advances are
      expected to find important applications in future stretchable and wearable
      electronics.

PMID- 29597267
TI  - Study on the Visible-Light Photocatalytic Performance and Degradation Mechanism
      of Diclofenac Sodium under the System of Hetero-Structural CuBi2O4/Ag3PO4 with
      H2O2.
AB  - Two kinds of CuBi2O4/Ag3PO4 with different heterojunction structures were
      prepared based on the combination of hydrothermal and in-situ precipitation
      methods with surfactant additives (sodium citrate and sodium stearate), and their
      characteristics were systematically resolved by X-ray Diffraction (XRD), Brunauer
      Emmett-Teller (BET), X-ray Photoelectron Spectroscopy (XPS), Scanning Electron
      Microscope (SEM)/ High-resolution Transmission Electron Microscopy (HRTEM), UV
      vis Diffuse Reflectance Spectra (DRS) and Photoluminescence (PL). Meanwhile, the
      photocatalytic properties of the catalysts were determined for diclofenac sodium
      (DS) degradation and the photocatalytic mechanism was also explored. The results
      indicate that both of the two kinds of CuBi2O4/Ag3PO4 exhibit higher
      photocatalytic efficiency, mineralization rate, and stability than that of pure
      CuBi2O4 or Ag3PO4. Moreover, the catalytic activity of CuBi2O4/Ag3PO4 can be
      further enhanced by adding H2O2. The free radical capture experiments show that
      in the pure CuBi2O4/Ag3PO4 photocatalytic system, the OH* and O2*- are the main
      species participating in DS degradation; however, in the CuBi2O4/Ag3PO4
      photocatalytic system with H2O2, all OH*, h+, and O2*- take part in the DS
      degradation, and the contribution order is OH* > h+ > O2*-. Accordingly, the
      photocatalytic mechanism of CuBi2O4/Ag3PO4 could be explained by the Z-Scheme
      theory, while the catalysis of CuBi2O4/Ag3PO4 with H2O2 follows the
      heterojunction energy band theory.

PMID- 29597266
TI  - The In Ovo Feeding Administration (Gallus Gallus)-An Emerging In Vivo Approach to
      Assess Bioactive Compounds with Potential Nutritional Benefits.
AB  - In recent years, the in ovo feeding in fertilized broiler (Gallus gallus) eggs
      approach was further developed and currently is widely applied in the evaluation
      process of the effects of functional foods (primarily plant origin compounds) on
      the functionality of the intestinal brush border membrane, as well as potential
      prebiotic properties and interactions with the intestinal microbial populations.
      This review collates the information of potential nutrients and their effects on
      the mineral absorption, gut development, brush border membrane functionality, and
      immune system. In addition, the advantages and limitations of the in ovo feeding
      method in the assessment of potential prebiotic effects of plant origin compounds
      is discussed.

PMID- 29597268
TI  - Antibacterial and Barrier Properties of Gelatin Coated by Electrospun
      Polycaprolactone Ultrathin Fibers Containing Black Pepper Oleoresin of Interest
      in Active Food Biopackaging Applications.
AB  - The present study evaluated the effect of using electrospun polycaprolactone
      (PCL) as a barrier coating and black pepper oleoresin (OR) as a natural extract
      on the morphology, thermal, mechanical, antimicrobial, oxygen, and water vapor
      barrier properties of solvent cast gelatin (GEL). The antimicrobial activity of
      the developed multilayer system obtained by the so-called electrospinning coating
      technique was also evaluated against Staphylococcus aureus strains for 10 days.
      The results showed that the multilayer system containing PCL and OR increased the
      thermal resistance, elongated the GEL film, and significantly diminished its
      permeance to water vapor. Active multilayer systems stored in hermetically closed
      bottles increased their antimicrobial activity after 10 days by inhibiting the
      growth of Staphylococcus aureus. This study demonstrates that addition of
      electrospun PCL ultrathin fibers and OR improved the properties of GEL films,
      which promoted its potential use in active food packaging applications.

PMID- 29597269
TI  - Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free
      Radical-Scavenging Activity.
AB  - Chitosan is an abundant and renewable polysaccharide, which exhibits attractive
      bioactivities and natural properties. Improvement such as chemical modification
      of chitosan is often performed for its potential of providing high bioactivity
      and good water solubility. A new class of chitosan derivatives possessing 1,2,3
      triazolium charged units by associating "click reaction" with efficient 1,2,3
      triazole quaternization were designed and synthesized. Their free radical
      scavenging activity against three free radicals was tested. The inhibitory
      property and water solubility of the synthesized chitosan derivatives exhibited a
      remarkable improvement over chitosan. It is hypothesized that triazole or
      triazolium groups enable the synthesized chitosan to possess obviously better
      radical-scavenging activity. Moreover, the scavenging activity against superoxide
      radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL-1) was more
      efficient than that of derivatives with triazole and Vitamin C. In the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging assay, the same
      pattern were observed, which should be related to the triazolium grafted at the
      periphery of molecular chains.

PMID- 29597270
TI  - Prediction of Tibial Rotation Pathologies Using Particle Swarm Optimization and K
      Means Algorithms.
AB  - The aim of this article is to investigate pathological subjects from a population
      through different physical factors. To achieve this, particle swarm optimization
      (PSO) and K-means (KM) clustering algorithms have been combined (PSO-KM).
      Datasets provided by the literature were divided into three clusters based on age
      and weight parameters and each one of right tibial external rotation (RTER),
      right tibial internal rotation (RTIR), left tibial external rotation (LTER), and
      left tibial internal rotation (LTIR) values were divided into three types as Type
      1, Type 2 and Type 3 (Type 2 is non-pathological (normal) and the other two types
      are pathological (abnormal)), respectively. The rotation values of every subject
      in any cluster were noted. Then the algorithm was run and the produced values
      were also considered. The values of the produced algorithm, the PSO-KM, have been
      compared with the real values. The hybrid PSO-KM algorithm has been very
      successful on the optimal clustering of the tibial rotation types through the
      physical criteria. In this investigation, Type 2 (pathological subjects) is of
      especially high predictability and the PSO-KM algorithm has been very successful
      as an operation system for clustering and optimizing the tibial motion data
      assessments. These research findings are expected to be very useful for health
      providers, such as physiotherapists, orthopedists, and so on, in which this
      consequence may help clinicians to appropriately designing proper treatment
      schedules for patients.

PMID- 29597271
TI  - PEG 400/Cerium Ammonium Nitrate Combined with Microwave-Assisted Synthesis for
      Rapid Access to Beta-Amino Ketones. An Easy-to-Use Protocol for Discovering New
      Hit Compounds.
AB  - Compound libraries are important requirement in target-based drug discovery. In
      the present work, a small focused compound library based on beta-aminoketone
      scaffold has been prepared combining microwave-assisted organic synthesis (MAOS)
      with polymer-assisted solution phase synthesis (PASPS) and replacing reaction
      workup standard purification procedures with solid phase extraction (SPE).
      Specifically, the effects of solvent, such as dioxane, dimethylformamide (DMF),
      polyethylene glycol 400 (PEG 400), temperature, irradiation time, stoichiometric
      ratio of reagents, and catalysts (HCl, acetic acid, cerium ammonium nitrate
      (CAN)) were investigated to maximize both conversion and yield. The optimized
      protocol generally afforded the desired products in satisfying yields and
      purities. The designed library is a part of our current research on sigma 1
      receptor modulators, a valuable tool for the identification of novel potential
      hit compounds.

PMID- 29597272
TI  - A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides.
AB  - Sepia ink polysaccharide (SIP) isolated from squid and cuttlefish ink is a kind
      of acid mucopolysaccharide that has been identified in three types of primary
      structures from squid (Illex argentinus and Ommastrephes bartrami), cuttlefish
      Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been
      proved to be multifaceted, most of the reported evidence has illuminated its
      chemopreventive and antineoplastic activities. As a natural product playing a
      role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or
      functional food. Based on the current findings on SIP, we have summarized four
      topics in this review, including: chemopreventive, antineoplastic,
      chemosensitive, and procoagulant and anticoagulant activities, which are
      correlative closely with the actions of anticancer agents on cancer patients,
      such as anticancer, toxicity and thrombogenesis, with the latter two actions
      being common causes of death in cancer cases exposed to chemotherapeutic agents.

PMID- 29597274
TI  - Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization
      Surface and Characterization of Three New Patients.
AB  - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mitochondrial
      HMG-CoA synthase deficiency or mHS deficiency, OMIM #605911) is an inborn error
      of metabolism that affects ketone body synthesis. Acute episodes include
      vomiting, lethargy, hepatomegaly, hypoglycemia and dicarboxylic aciduria. The
      diagnosis is difficult due to the relatively unspecific clinical and biochemical
      presentation, and fewer than 30 patients have been described. This work describes
      three new patients with mHS deficiency and two missense mutations c.334C>T
      (p.R112W) and c.430G>T (p.V144L) previously not reported. We developed a new
      method to express and measure the activity of the enzyme and in this work the
      study is extended to ten new missense variants including those of our patients.
      Enzymatic assays showed that three of the mutant proteins retained some but seven
      completely lacked activity. The identification of a patient homozygous for a
      mutation that retains 70% of enzyme activity opens the door to a new
      interpretation of the disease by demonstrating that a modest impairment of enzyme
      function can actually produce symptoms. This is also the first study employing
      molecular dynamics modelling of the enzyme mutations. We show that the correct
      maintenance of the dimerization surface is crucial for retaining the structure of
      the active center and therefore the activity of the enzyme.

PMID- 29597275
TI  - Graphene Quantum Dots-ZnS Nanocomposites with Improved Photoelectric
      Performances.
AB  - ZnS-graphene quantum dot (GQDs) composites were synthesized by a simple
      solvothermal method, in which GQDs were prepared by a hydrothermal cutting
      process. The products were characterized by transmission electron microscopy,
      atomic force microscopy, X-ray diffraction and ultraviolet-visible absorption
      spectroscopy. The results show that GQDs were obtained by size tailoring of 1-4
      graphene layers and combined with cubic ZnS nanoparticles to form ZnS-GQDs
      composites. The photocurrent and electrochemical behavior of the products were
      evaluated by transient photocurrent responses and electrochemical impedance
      spectra. The photocurrent density of ZnS-GQDs achieves the value of 2.32 * 10-5
      A/cm2, which is 2.4-times as high as that of ZnS-graphene. GQDs serve as an
      electrical conducting material, which decreases the conductive path and
      accelerates the electron transfer. The charge-transfer resistance of ZnS-GQDs is
      much lower than that of ZnS-graphene and pure ZnS due to the effective electron
      separation and transfer ability upon the incorporation of GQDs.

PMID- 29597273
TI  - Nutrition-Related Knowledge, Attitudes, and Practices (KAP) among Kindergarten
      Teachers in Chongqing, China: A Cross-Sectional Survey.
AB  - Kindergarten teachers play an important role in providing kindergarten children
      with education on nutrition. However, few studies have been published on
      nutrition-related knowledge, attitudes, and practices (KAP) of Chinese
      kindergarten teachers. This study aimed to assess the nutrition-related
      knowledge, attitudes, and practices (KAP) of kindergarten teachers in Chongqing,
      China. Thus, a cross-sectional survey was conducted using a structured KAP model
      questionnaire administered to 222 kindergarten teachers, who were senior teachers
      from 80 kindergartens in 19 districts and 20 counties in Chongqing. Multiple
      regression analysis was used to analyze the influential factors. Among the
      participants, 54.2% were familiar with simple nutrition-related knowledge; only
      9.9% of them were satisfied with their knowledge of childhood nutrition; and
      97.7% of them had a positive attitude to learn nutrition-related knowledge. Only
      38.7% of the participants had attended pediatric nutrition knowledge courses or
      training. Multiple regression analysis confirmed significant independent effects
      on the nutrition knowledge score (p < 0.0001) of respondents on age, type of
      residence, type of kindergarten, body mass index(BMI), professional training of
      kindergarten teachers, behavior of having ever participated in childhood
      nutrition education knowledge courses or training, and behavior of having ever
      paid attention to children's nutrition knowledge. The model indicated that
      independent variables explained 45.4% (adjusted R2) of the variance found in the
      knowledge scores of respondents. While there were low levels of nutrition
      knowledge and training, it was still encouraging to note that there were positive
      attitudes towards acquiring nutrition-related knowledge among kindergarten
      teachers in Chongqing, China. These findings provide some implications that
      necessary training measures need to be carried out to improve the nutrition
      related knowledge level among kindergarten teachers in China.

PMID- 29597276
TI  - Linear Feature Projection-Based Sensory Event Detection from the Multiunit
      Activity of Dorsal Root Ganglion Recordings.
AB  - Afferent signals recorded from the dorsal root ganglion can be used to extract
      sensory information to provide feedback signals in a functional electrical
      stimulation (FES) system. The goal of this study was to propose an efficient
      feature projection method for detecting sensory events from multiunit activity
      based feature vectors of tactile afferent activity. Tactile afferent signals were
      recorded from the L4 dorsal root ganglion using a multichannel microelectrode for
      three types of sensory events generated by mechanical stimulation on the rat hind
      paw. The multiunit spikes (MUSs) were extracted as multiunit activity-based
      feature vectors and projected using a linear feature projection method which
      consisted of projection pursuit and negentropy maximization (PP/NEM). Finally, a
      multilayer perceptron classifier was used to detect sensory events. The proposed
      method showed a detection accuracy superior to those of other linear and
      nonlinear feature projection methods and all processes were completed within real
      time constraints. Results suggest that the proposed method could be useful to
      detect sensory events in real time. We have demonstrated the methodology for an
      efficient feature projection method to detect real-time sensory events from the
      multiunit activity of dorsal root ganglion recordings. The proposed method could
      be applied to provide real-time sensory feedback signals in closed-loop FES
      systems.

PMID- 29597277
TI  - Potential of Silicon Amendment for Improved Wheat Production.
AB  - Many studies throughout the world have shown positive responses of various crops
      to silicon (Si) application in terms of plant health, nutrient uptake, yield, and
      quality. Although not considered an essential element for plant growth, Si has
      been recently recognized as a "beneficial substance" or "quasi-essential" due to
      its important role in plant nutrition, especially notable under stressed
      conditions. The goal of this study was to evaluate the effect of Si on wheat
      plant height, grain yield (GY), and grain protein content (GP). The experiment
      was conducted during two consecutive growing seasons in Idaho. A split-plot
      experimental design was used with three Si fertilization rates (140, 280, and 560
      kg Si ha-1) corresponding to 100, 50, and 25% of manufacturer-recommended rates
      and two application times-at planting and tillering (Feekes 5). MontanaGrowTM (0
      0-5) by MontanaGrow Inc. (Bonner, MT, USA) used in this study is a Si product
      sourced from a high-energy amorphous (non-crystalized) volcanic tuff. There was
      no significant effect of Si rate and application time on plant height, nutrient
      uptake, GY, or GP of irrigated winter wheat grown in non-stressed conditions.
      These results could be directly related to the Si fertilizer source used in the
      study. We are planning to further evaluate Si's effect on growth and grain
      production of wheat grown in non-stressed vs. stressed conditions utilizing
      several different Si sources and application methods.

PMID- 29597278
TI  - Ratcheting Strain and Microstructure Evolution of AZ31B Magnesium Alloy under a
      Tensile-Tensile Cyclic Loading.
AB  - In this paper, studies were conducted to investigate the deformation behavior and
      microstructure change in a hot-rolled AZ31B magnesium alloy during a tensile
      tensile cyclic loading. The relationship between ratcheting effect and
      microstructure change was discussed. The ratcheting effect in the material during
      current tensile-tensile fatigue loading exceeds the material's fatigue limit and
      the development of ratcheting strain in the material experienced three stages:
      initial sharp increase stage (Stage I); steady stage (Stage II); and final abrupt
      increase stage (Stage III). Microstructure changes in Stage I and Stage II are
      mainly caused by activation of basal slip system. The Extra Geometrically
      Necessary Dislocations (GNDs) were also calculated to discuss the relationship
      between the dislocation caused by the basal slip system and the ratcheting strain
      during the cyclic loading. In Stage III, both the basal slip and the {11-20}
      twins are found active during the crack propagation. The fatigue crack initiation
      in the AZ31B magnesium alloy is found due to the basal slip and the {11-20}
      tensile twins.

PMID- 29597280
TI  - A Sparsity-Promoted Method Based on Majorization-Minimization for Weak Fault
      Feature Enhancement.
AB  - Fault transient impulses induced by faulty components in rotating machinery
      usually contain substantial interference. Fault features are comparatively weak
      in the initial fault stage, which renders fault diagnosis more difficult. In this
      case, a sparse representation method based on the Majorzation-Minimization (MM)
      algorithm is proposed to enhance weak fault features and extract the features
      from strong background noise. However, the traditional MM algorithm suffers from
      two issues, which are the choice of sparse basis and complicated calculations. To
      address these challenges, a modified MM algorithm is proposed in which a sparse
      optimization objective function is designed firstly. Inspired by the Basis
      Pursuit (BP) model, the optimization function integrates an impulsive feature
      preserving factor and a penalty function factor. Second, a modified Majorization
      iterative method is applied to address the convex optimization problem of the
      designed function. A series of sparse coefficients can be achieved through
      iterating, which only contain transient components. It is noteworthy that there
      is no need to select the sparse basis in the proposed iterative method because it
      is fixed as a unit matrix. Then the reconstruction step is omitted, which can
      significantly increase detection efficiency. Eventually, envelope analysis of the
      sparse coefficients is performed to extract weak fault features. Simulated and
      experimental signals including bearings and gearboxes are employed to validate
      the effectiveness of the proposed method. In addition, comparisons are made to
      prove that the proposed method outperforms the traditional MM algorithm in terms
      of detection results and efficiency.

PMID- 29597279
TI  - The Hippo Pathway: Immunity and Cancer.
AB  - Since its discovery, the Hippo pathway has emerged as a central signaling network
      in mammalian cells. Canonical signaling through the Hippo pathway core components
      (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue
      homeostasis while aberrant signaling through the Hippo pathway has been
      implicated in multiple pathologies, including cancer. Recent studies have
      uncovered new roles for the Hippo pathway in immunology. In this review, we
      summarize the mechanisms by which Hippo signaling in pathogen-infected or
      neoplastic cells affects the activities of immune cells that respond to these
      threats. We further discuss how Hippo signaling functions as part of an immune
      response. Finally, we review how immune cell-intrinsic Hippo signaling modulates
      the development/function of leukocytes and propose directions for future work.

PMID- 29597281
TI  - Evaluating Muscle Activation Models for Elbow Motion Estimation.
AB  - Adoption of wearable assistive technologies relies heavily on improvement of
      existing control system models. Knowing which models to use and how to improve
      them is difficult to determine due to the number of proposed solutions with
      relatively little broad comparisons. One type of these models, muscle activation
      models, describes the nonlinear relationship between neural inputs and mechanical
      activation of the muscle. Many muscle activation models can be found in the
      literature, but no comparison is available to guide the community on limitations
      and improvements. In this research, an EMG-driven elbow motion model is developed
      for the purpose of evaluating muscle activation models. Seven muscle activation
      models are used in an optimization procedure to determine which model has the
      best performance. Root mean square errors in muscle torque estimation range from
      1.67-2.19 Nm on average over varying input trajectories. The computational
      resource demand was also measured during the optimization procedure, as it is an
      important aspect for determining if a model is feasible for use in a particular
      wearable assistive device. This study provides insight into the ability of these
      models to estimate elbow motion and the trade-off between estimation accuracy and
      computational demand.

PMID- 29597283
TI  - Individual Biometric Identification Using Multi-Cycle Electrocardiographic
      Waveform Patterns.
AB  - The electrocardiogram (ECG) waveform conveys information regarding the electrical
      property of the heart. The patterns vary depending on the individual heart
      characteristics. ECG features can be potentially used for biometric recognition.
      This study presents a new method using the entire ECG waveform pattern for
      matching and demonstrates that the approach can potentially be employed for
      individual biometric identification. Multi-cycle ECG signals were assessed using
      an ECG measuring circuit, and three electrodes can be patched on the wrists or
      fingers for considering various measurements. For biometric identification, our
      fold cross validation was used in the experiments for assessing how the results
      of a statistical analysis will generalize to an independent data set. Four
      different pattern matching algorithms, i.e., cosine similarity, cross
      correlation, city block distance, and Euclidean distances, were tested to compare
      the individual identification performances with a single channel of ECG signal (3
      wire ECG). To evaluate the pattern matching for biometric identification, the ECG
      recordings for each subject were partitioned into training and test set. The
      suggested method obtained a maximum performance of 89.9% accuracy with two
      heartbeats of ECG signals measured on the wrist and 93.3% accuracy with three
      heartbeats for 55 subjects. The performance rate with ECG signals measured on the
      fingers improved up to 99.3% with two heartbeats and 100% with three heartbeats
      of signals for 20 subjects.

PMID- 29597282
TI  - Identification of Leaf Promoters for Use in Transgenic Wheat.
AB  - Wheat yields have plateaued in recent years and given the growing global
      population there is a pressing need to develop higher yielding varieties to meet
      future demand. Genetic manipulation of photosynthesis in elite wheat varieties
      offers the opportunity to significantly increase yields. However, the absence of
      a well-defined molecular tool-box of promoters to manipulate leaf processes in
      wheat hinders advancements in this area. Two promoters, one driving the
      expression of sedoheptulose-1,7-bisphosphatase (SBPase) and the other fructose
      1,6-bisphosphate aldolase (FBPA) from Brachypodium distachyon were identified and
      cloned into a vector in front of the GUS reporter gene. Both promoters were shown
      to be functionally active in wheat in both transient assays and in stably
      transformed wheat plants. Analysis of the stable transformants of wheat (cv.
      Cadenza) showed that both promoters controlled gus expression throughout leaf
      development as well as in other green tissues. The availability of these
      promoters provides new tools for the expression of genes in transgenic wheat
      leaves and also paves the way for multigene manipulation of photosynthesis to
      improve yields.

PMID- 29597284
TI  - PSPICE Hybrid Modeling and Simulation of Capacitive Micro-Gyroscopes.
AB  - With an aim to reduce the cost of prototype development, this paper establishes a
      PSPICE hybrid model for the simulation of capacitive microelectromechanical
      systems (MEMS) gyroscopes. This is achieved by modeling gyroscopes in different
      modules, then connecting them in accordance with the corresponding principle
      diagram. Systematic simulations of this model are implemented along with a
      consideration of details of MEMS gyroscopes, including a capacitance model
      without approximation, mechanical thermal noise, and the effect of ambient
      temperature. The temperature compensation scheme and optimization of interface
      circuits are achieved based on the hybrid closed-loop simulation of MEMS
      gyroscopes. The simulation results show that the final output voltage is
      proportional to the angular rate input, which verifies the validity of this
      model.

PMID- 29597285
TI  - A Novel GMM-Based Behavioral Modeling Approach for Smartwatch-Based Driver
      Authentication.
AB  - All drivers have their own distinct driving habits, and usually hold and operate
      the steering wheel differently in different driving scenarios. In this study, we
      proposed a novel Gaussian mixture model (GMM)-based method that can improve the
      traditional GMM in modeling driving behavior. This new method can be applied to
      build a better driver authentication system based on the accelerometer and
      orientation sensor of a smartwatch. To demonstrate the feasibility of the
      proposed method, we created an experimental system that analyzes driving behavior
      using the built-in sensors of a smartwatch. The experimental results for driver
      authentication-an equal error rate (EER) of 4.62% in the simulated environment
      and an EER of 7.86% in the real-traffic environment-confirm the feasibility of
      this approach.

PMID- 29597286
TI  - A Large-Scale Study of Fingerprint Matching Systems for Sensor Interoperability
      Problem.
AB  - The fingerprint is a commonly used biometric modality that is widely employed for
      authentication by law enforcement agencies and commercial applications. The
      designs of existing fingerprint matching methods are based on the hypothesis that
      the same sensor is used to capture fingerprints during enrollment and
      verification. Advances in fingerprint sensor technology have raised the question
      about the usability of current methods when different sensors are employed for
      enrollment and verification; this is a fingerprint sensor interoperability
      problem. To provide insight into this problem and assess the status of state-of
      the-art matching methods to tackle this problem, we first analyze the
      characteristics of fingerprints captured with different sensors, which makes
      cross-sensor matching a challenging problem. We demonstrate the importance of
      fingerprint enhancement methods for cross-sensor matching. Finally, we conduct a
      comparative study of state-of-the-art fingerprint recognition methods and provide
      insight into their abilities to address this problem. We performed experiments
      using a public database (FingerPass) that contains nine datasets captured with
      different sensors. We analyzed the effects of different sensors and found that
      cross-sensor matching performance deteriorates when different sensors are used
      for enrollment and verification. In view of our analysis, we propose future
      research directions for this problem.

PMID- 29597287
TI  - Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and
      Obesity: A Family-Based Study in China.
AB  - C-Maf Inducing Protein (CMIP) gene polymorphisms were reported to be associated
      with type 2 diabetes mellitus (T2DM). Whether the association between CMIP and
      T2DM is mediated via obesity-related phenotypes is still unclear. We analyzed the
      association of CMIP rs2925979 with T2DM and a comprehensive set of obesity
      related phenotypes in 1576 families ascertained from a Chinese population. These
      families included a total of 3444 siblings (1582 with T2DM, 963 with prediabetes,
      and 899 with a normal glucose level). Using multi-level mixed effects regression
      models, we found that each copy of CMIP rs2925979_T allele was associated with a
      29% higher risk of T2DM in females (p = 9.30 * 10-4), while it was not
      significantly associated with T2DM in males (p = 0.705). Meanwhile, rs2925979_T
      allele was associated with lower levels of body mass index (BMI), waist
      circumference (WC), hip circumference (HC), percentage of body fat (PBF), PBF of
      arms, PBF of legs, and PBF of trunk in nondiabetes females (all p < 0.05). The
      opposite associations of rs2925979_T allele with T2DM and obesity-related
      phenotypes suggest that CMIP may exert independent pleiotropic effects on T2DM
      and obesity-related phenotypes in females.

PMID- 29597288
TI  - Selective Adsorption of Pb(II) from Aqueous Solution by Triethylenetetramine
      Grafted Polyacrylamide/Vermiculite.
AB  - Amine groups play significant roles in polymeric composites for heavy metals
      removal. However, generating a composite with a large number of functional and
      stable amine groups based on clay is still a challenge. In this work, a new amine
      functionalized adsorbent based on acid-activated vermiculite (a-Verm) was
      prepared by organic modification of silane coupling agent as bridge, followed by
      in situ polymerization of acrylamide (AM) and further grafting of triethylene
      tetramine (TETA). The obtained polymeric composite g-PAM/OVerm was characterized
      by scanning electron microscope (SEM), energy dispersive spectrometer (EDS),
      Fourier transform infrared (FTIR), thermal analysis (TG/DTG), X-ray photoelectron
      spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) analyses, confirming that
      amine groups were successfully grafted onto the surface of Verm. The efficacy g
      PAM/OVerm for removing Pb(II) was tested. The adsorption equilibrium data on g
      PAM/OVerm was in good accordance with the Langmuir adsorption isotherms, and the
      adsorption maximal value of Pb(II) was 219.4 mg.g-1. The adsorption kinetic data
      fit the pseudo-second-order kinetic model well. Additionally, g-PAM/OVerm has
      better selectivity for Pb(II) ion in comparison with Zn(II), Cd(II) and Cu(II)
      ions. The present work shows that g-PAM/OVerm holds great potential for removing
      Pb(II) from wastewater, and provides a new and efficient method for the removal
      of heavy metal ions from industrial wastewater.

PMID- 29597289
TI  - The Epidemiology of Unintentional and Violence-Related Injury Morbidity and
      Mortality among Children and Adolescents in the United States.
AB  - Injuries and violence among young people have a substantial emotional, physical,
      and economic toll on society. Understanding the epidemiology of this public
      health problem can guide prevention efforts, help identify and reduce risk
      factors, and promote protective factors. We examined fatal and nonfatal
      unintentional injuries, injuries intentionally inflicted by other (i.e., assaults
      and homicides) among children ages 0-19, and intentionally self-inflicted
      injuries (i.e., self-harm and suicides) among children ages 10-19. We accessed
      deaths (1999-2015) and visits to emergency departments (2001-2015) for these age
      groups through the Centers for Disease Control and Prevention's (CDC) Web-based
      Injury Statistics Query and Reporting System (WISQARS), and examined trends and
      differences by age, sex, race/ethnicity, rural/urban status, and injury
      mechanism. Almost 13,000 children and adolescents age 0-19 years died in 2015
      from injury and violence compared to over 17,000 in 1999. While the overall
      number of deaths has decreased over time, there were increases in death rates
      among certain age groups for some categories of unintentional injury and for
      suicides. The leading causes of injury varied by age group. Our results indicate
      that efforts to reduce injuries to children and adolescents should consider
      cause, intent, age, sex, race, and regional factors to assure that prevention
      resources are directed at those at greatest risk.

PMID- 29597290
TI  - Genome-Wide Identification of the Alba Gene Family in Plants and Stress
      Responsive Expression of the Rice Alba Genes.
AB  - Architectural proteins play key roles in genome construction and regulate the
      expression of many genes, albeit the modulation of genome plasticity by these
      proteins is largely unknown. A critical screening of the architectural proteins
      in five crop species, viz., Oryza sativa, Zea mays, Sorghum bicolor, Cicer
      arietinum, and Vitis vinifera, and in the model plant Arabidopsis thaliana along
      with evolutionary relevant species such as Chlamydomonas reinhardtii,
      Physcomitrella patens, and Amborella trichopoda, revealed 9, 20, 10, 7, 7, 6, 1,
      4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A
      phylogenetic analysis of the genes and of their counterparts in other plant
      species indicated evolutionary conservation and diversification. In each group,
      the structural components of the genes and motifs showed significant
      conservation. The chromosomal location of the Alba genes of rice (OsAlba), showed
      an unequal distribution on 8 of its 12 chromosomes. The expression profiles of
      the OsAlba genes indicated a distinct tissue-specific expression in the seedling,
      vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR)
      analysis of the OsAlba genes confirmed their stress-inducible expression under
      multivariate environmental conditions and phytohormone treatments. The evaluation
      of the regulatory elements in 68 Alba genes from the 9 species studied led to the
      identification of conserved motifs and overlapping microRNA (miRNA) target sites,
      suggesting the conservation of their function in related proteins and a
      divergence in their biological roles across species. The 3D structure and the
      prediction of putative ligands and their binding sites for OsAlba proteins
      offered a key insight into the structure-function relationship. These results
      provide a comprehensive overview of the subtle genetic diversification of the
      OsAlba genes, which will help in elucidating their functional role in plants.

PMID- 29597291
TI  - Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71
      Infection.
AB  - Enterovirus 71 (EV71) infection has become a major threat to global public
      health, especially in infants and young children. Epidemiological studies have
      indicated that EV71 infection is responsible for severe and even fatal cases of
      hand, foot, and mouth disease (HFMD). Accumulated evidence indicates that EV71
      infection triggers a plethora of interactive signaling pathways, resulting in
      host immune evasion and inflammatory response. This review mainly covers the
      effects of EV71 infection on major antiviral and inflammatory cellular signal
      pathways. EV71 can activate cellular signaling networks including multiple cell
      surface and intracellular receptors, intracellular kinases, calcium flux, and
      transcription factors that regulate antiviral innate immunity and inflammatory
      response. Cellular signaling plays a critical role in the regulation of host
      innate immune and inflammatory pathogenesis. Elucidation of antiviral and
      inflammatory cellular signaling pathways initiated by EV71 will not only help
      uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will
      also provide clues for the design of therapeutic strategies against EV71
      infection.

PMID- 29597292
TI  - Comparison of Commensal Escherichia coli Isolates from Adults and Young Children
      in Lubuskie Province, Poland: Virulence Potential, Phylogeny and Antimicrobial
      Resistance.
AB  - Commensal Escherichia coli population is a dynamic structure which may be
      important in the pathogenesis of extraintestinal infections. The aim of this
      study was the comparison of genetic diversity of commensal E. coli isolates from
      two age group-adults and young children. E. coli strains were isolated on
      MacConkey agar and identified by biochemical tests. Determination of four major
      phylogenetic groups, identification of virulence genes and antimicrobial
      resistance determinants were performed by using multiplex or simplex PCR.
      Phenotypic analysis of resistance was based on disc-diffusion method. The
      prevalence of virulence genes was significantly higher among isolates from adults
      than from young children. Phylogroup B2 predominated among E. coli from adults,
      whereas phylogroup A was the most common in isolates from young children. The
      analyses of antimicrobial resistance revealed that resistance to at least one
      antimicrobial agent and multidrug-resistance were detected significantly more
      frequent in the isolates from adults than from young children. This study
      documented that the commensal E. coli isolates from adults showed greater genetic
      diversity than from young children and constitutes a substantial reservoir of the
      virulence genes typical for extraintestinal pathogenic E. coli.

PMID- 29597293
TI  - Transcriptome Analysis Reveals Molecular Signatures of Luteoloside Accumulation
      in Senescing Leaves of Lonicera macranthoides.
AB  - Lonicera macranthoides is an important medicinal plant widely used in traditional
      Chinese medicine. Luteoloside is a critical bioactive compound in L.
      macranthoides. To date, the molecular mechanisms underlying luteoloside
      biosynthesis are still largely unknown. In this work, high performance liquid
      chromatography (HPLC) was employed to determine the luteoloside contents in
      leaves, stems, and flowers at different developmental stages. Results showed that
      senescing leaves can accumulate large amounts of luteoloside, extremely higher
      than that in young and semi-lignified leaves and other tissues. RNA-Seq analysis
      identified that twenty-four differentially expressed unigenes (DEGs) associated
      with luteoloside biosynthesis were significantly up-regulated in senescing
      leaves, which are positively correlated with luteoloside accumulation. These DEGs
      include phenylalanine ammonia lyase 2, cinnamate 4-hydroxylase 2, thirteen 4
      coumarate-CoA ligases, chalcone synthase 2, six flavonoid 3'-monooxygenase (F3'H)
      and two flavone 7-O-beta-glucosyltransferase (UFGT) genes. Further analysis
      demonstrated that two F3'Hs (CL11828.Contig1 and CL11828.Contig2) and two UFGTs
      (Unigene2918 and Unigene97915) might play vital roles in luteoloside generation.
      Furthermore, several transcription factors (TFs) related to flavonoid
      biosynthesis including MYB, bHLH and WD40, were differentially expressed during
      leaf senescence. Among these TFs, MYB12, MYB75, bHLH113 and TTG1 were considered
      to be key factors involved in the regulation of luteoloside biosynthesis. These
      findings provide insights for elucidating the molecular signatures of luteoloside
      accumulation in L. macranthoides.

PMID- 29597294
TI  - Engineering the Salt-Inducible Ectoine Promoter Region of Halomonas elongata for
      Protein Expression in a Unique Stabilizing Environment.
AB  - It has been firmly established that organic osmolytes (compatible solutes) of
      halophilic Bacteria and Archaea have positive effects on conformation and
      activity of proteins, and may therefore improve their functional production. In
      particular, the amino acid derivative ectoine is known for its conformational
      stabilization, aggregation suppression, and radical protection properties. The
      natural producer and industrial production strain Halomonas elongata accumulates
      ectoine in the cytoplasm, and as a result offers a unique stabilizing environment
      for recombinant proteins. For the construction of broad hoast range vector
      systems with fluorescent reporter proteins, we chose the salt-inducible promoter
      region of the ectoine gene cluster (promA). A closer inspection of the genetic
      background revealed that its combination of sigma 38 (sigma38) and sigma 70
      (sigma70) promoters was followed by a weak ribosomal binding site (RBS). This
      inspired a systematic approach for the construction of a promA-based vector
      series with a synthetic RBS region using the RBS Calculator v2.0, which resulted
      in a greatly improved salt-dependent expression-even in a deletion construct
      lacking the sigma38 promoter. To expand the application range of this expression
      system, we looked further into the possible export of recombinant proteins into
      the periplasm. Both sec and tat leader sequences from H. elongata proved to be
      suitable for directed periplasmic transport into an extreme environment of freely
      selectable ionic strength.

PMID- 29597295
TI  - Functionalized Gold Nanoparticles for the Detection of C-Reactive Protein.
AB  - C-reactive protein (CRP) is a very important biomarker of infection and
      inflammation for a number of diseases. Routine CRP measurements with high
      sensitivity and reliability are highly relevant to the assessment of states of
      inflammation and the efficacy of treatment intervention, and require the
      development of very sensitive, selective, fast, robust and reproducible assays.
      Gold nanoparticles (Au NPs) are distinguished for their unique electrical and
      optical properties and the ability to conjugate with biomolecules. Au NP-based
      probes have attracted considerable attention in the last decade in the analysis
      of biological samples due to their simplicity, high sensitivity and selectivity.
      Thus, this article aims to be a critical and constructive analysis of the
      literature of the last three years regarding the advances made in the development
      of bioanalytical assays based on gold nanoparticles for the in vitro detection
      and quantification of C-reactive protein from biological samples. Current methods
      for Au NP synthesis and the strategies for surface modification aiming at
      selectivity towards CRP are highlighted.

PMID- 29597296
TI  - Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S
      Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells.
AB  - Silkworm pupae (Bombyx mori) are a high-protein nutrition source consumed in
      China since more than 2 thousand years ago. Recent studies revealed that silkworm
      pupae have therapeutic benefits to treat many diseases. However, the ability of
      the compounds of silkworm pupae to inhibit tumourigenesis remains to be
      elucidated. Here, we separated the protein of silkworm pupae and performed
      alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH) can specifically
      inhibit the proliferation and provoke abnormal morphologic features of human
      gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover,
      flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle
      in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive
      oxygen species (ROS) and depolarization of mitochondrial membrane potential.
      Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and
      promoted Bax expression, and subsequently induced apoptosis-inducing factor and
      cytochrome C release, which led to the activation of initiator caspase-9 and
      executioner caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP),
      eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was
      mediated by up-regulating the expression of E2F1 and down-regulating those of
      cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment
      analysis (GSEA) also revealed that SPPH treatment could affect gene expression
      and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In
      summary, our results suggest that SPPH could specifically suppress cell growth of
      SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle
      arrest, and silkworm pupae have a potential to become a source of anticancer
      agents in the future.

PMID- 29597297
TI  - Parents' Experiences of Suicide-Bereavement: A Qualitative Study at 6 and 12
      Months after Loss.
AB  - The death of a child by suicide is a severe trauma, placing parents at greater
      risk of psychological morbidity and physical health problems compared to other
      causes of death. However, few studies have examined the aftermath and bereavement
      experience for parents following the death of a child to suicide, limiting the
      ability to guide effective postvention services through empirical research. The
      current study, which was part of a larger longitudinal investigation of suicide
      bereavement in Queensland, Australia, examined the individual experiences of both
      mothers and fathers bereaved by suicide over time, specifically at the six month
      and 12 month time points after their loss. Bereaved parents who had provided
      written consent to be contacted for research purposes were identified through the
      Queensland Suicide Register, and took part in individual, semi-structured
      interviews. Generic qualitative analysis identified three key themes: searching
      for answers and sense-making, coping strategies and support, and finding meaning
      and purpose. Some participants showed indications of meaning-making and post
      traumatic growth at 12 months after the suicide. According to the dual process
      model of bereavement, it is likely that participants were still oscillating
      between sense-making and meaning making, indicating that adapting to bereavement
      is a dynamic and fluctuating process.

PMID- 29597298
TI  - Probing Interactions between AuNPs/AgNPs and Giant Unilamellar Vesicles (GUVs)
      Using Hyperspectral Dark-field Microscopy.
AB  - Noble metallic nanoparticles (NPs) such as gold and silver nanoparticles (AuNPs
      and AgNPs) have been shown to exhibit anti-tumor effect in anti-angiogenesis,
      photothermal and radio therapeutics. On the other hand, cell membranes are
      critical locales for specific targeting of cancerous cells. Therefore, NP
      membrane interactions need be studied at molecular level to help better
      understand the underlying physicochemical mechanisms for future applications in
      cancer nanotechnology. Herein, we report our study on the interactions between
      citrate stabilized colloidal AuNPs/AgNPs (10 nm in size) and giant unilamellar
      vesicles (GUVs) using hyperspectral dark-field microscopy. GUVs are large model
      vesicle systems well established for the study of membrane dynamics. GUVs used in
      this study were prepared with dimyristoyl phosphatidylcholine (DMPC) and doped
      with cholesterol at various molar concentrations. Both imaging and spectral
      results support that AuNPs and AgNPs interact very differently with GUVs, i.e.,
      AuNPs tend to integrate in between the lipid bilayer and form a uniform golden
      brown crust on vesicles, whereas AgNPs are bejeweled on the vesicle surface as
      isolated particles or clusters with much varied configurations. The more
      disruptive capability of AuNPs is hypothesized to be responsible for the
      formation of golden brown crusts in AuNP-GUV interaction. GUVs of 20 mol%
      CHOL:DMPC were found to be a most economical concentration for GUVs to achieve
      the best integrity and the least permeability, consistent with the finding from
      other phase studies of lipid mixture that the liquid-ordered domains have the
      largest area fraction of the entire membrane at around 20 mol% of cholesterol.

PMID- 29597299
TI  - Synthesis and Antiproliferative Activity of Minor Hops Prenylflavonoids and New
      Insights on Prenyl Group Cyclization.
AB  - Synthesis of minor prenylflavonoids found in hops and their non-natural
      derivatives were performed. The antiproliferative activity of the obtained
      compounds against some human cancer cell lines was investigated. Using
      xanthohumol isolated from spent hops as a lead compound, a series of minor hop
      prenylflavonoids and synthetic derivatives were obtained by isomerization,
      cyclisation, oxidative-cyclisation, oxidation, reduction and demethylation
      reactions. Three human cancer cell lines-breast (MCF-7), prostate (PC-3) and
      colon (HT-29)-were used in antiproliferative assays, with cisplatin as a control
      compound. Five minor hop prenyl flavonoids and nine non-natural derivatives of
      xanthohumol have been synthetized. Syntheses of xanthohumol K, its dihydro- and
      tetrahydro-derivatives and 1",2",alpha,beta-tetrahydroxanthohumol C were
      described for the first time. All of the minor hops prenyl flavonoids exhibited
      strong to moderate antiproliferative activity in vitro. The minor hops flavonoids
      xanthohumol C and 1",2"-dihydroxanthohumol K and non-natural 2,3
      dehydroisoxanthohumol exhibited the activity comparable to cisplatin. Results
      described in the article suggest that flavonoids containing chromane- and
      chromene-like moieties, especially chalcones, are potent antiproliferative
      agents. The developed new efficient, regioselective cyclisation reaction of the
      xanthohumol prenyl group to 1",2"-dihydroxantohumol K may be used in the
      synthesis of other compounds with the chromane moiety.

PMID- 29597301
TI  - Synthesis of Novel Amino Acid-Fipronil Conjugates and Study on Their Phloem
      Loading Mechanism.
AB  - To develop a new pesticide with phloem mobility, a series of new amino acid
      fipronil conjugates were designed and synthesized based on derivatization at the
      3-position of the pyrazole ring of fipronil. Experiments using a Ricinus communis
      seedling system showed that all tested conjugates were phloem mobile except for
      the isoleucine-fipronil conjugate, and that the serine-fipronil conjugate (4g)
      exhibited the highest concentration in phloem sap (52.00 +/- 5.80 MUM). According
      to prediction with log Cf values and uptake experiments with Xenopus oocytes, the
      phloem loading process of conjugate 4g involved both passive diffusion and an
      active carrier system (RcANT15). In particular, compared with for a previously
      reported glycinergic-fipronil conjugate (GlyF), passive diffusion played a more
      important role for conjugate 4g in the enhancement of phloem mobility. This study
      suggests that associating a nutrient at a different position of an existing
      pesticide structure could still be effective in obtaining phloem-mobile
      derivatives, but the distinct physicochemical properties of resultant conjugates
      may lead to different phloem loading mechanisms.

PMID- 29597302
TI  - Effects of Basal Defoliation on Wine Aromas: A Meta-Analysis.
AB  - Basal defoliation, as one of the most common viticulture management practices to
      modify fruit zone microclimates, has been widely applied aiming at improving wine
      quality. Wine aroma contributes greatly to wine quality, yet the effects of basal
      defoliation on wine aromas show discrepancies according to previous studies. This
      study is a meta-analysis performed to dissect the factors related to the
      influence of basal defoliation on volatile compounds in wine. Timing of basal
      defoliation plays an important role in the concentration of varietal aromas in
      wine. Pre-veraison defoliation induces an increase in beta-damascenone and
      linalool as well as a reduction in 3-isobutyl-2-methoxypyrazine (IBMP). The
      effects of basal defoliation on certain volatile compounds relative to
      fermentation aromas in wine (1-hexanol, beta-phenylethanol, 2-phenylethyl
      acetate, decanoic acid, and ethyl octanoate) depend on grape maturity. There are
      also other factors, such as cultivar and climate conditions, that might be
      responsible for the effect of basal defoliation on wine aromas. The
      concentrations of isobutanol, isoamyl alcohol, hexanoic acid, and octanoic acid
      as well as ethyl isobutyrate, ethyl hexanoate, ethyl isovalerate, and ethyl
      decanoate in wine are not markedly affected by basal defoliation. Due to limited
      studies included in this meta-analysis, more trials are needed to confirm the
      current findings.

PMID- 29597303
TI  - Sensory Characteristics of Various Concentrations of Phenolic Compounds
      Potentially Associated with Smoked Aroma in Foods.
AB  - This research describes the sensory odor characteristics of 19 phenolic compounds
      (11 phenol derivatives, six guaiacol derivatives, and two syringol derivatives)
      that have been associated with smoked aroma in previous literature. Seven
      concentrations varying from 1 to 100,000 ppm of each chemical were examined. A
      highly trained descriptive panel used a recently published lexicon for smoky
      aroma and flavor and found that smoked aroma compounds have many different
      attributes that make up smokiness. Musty/dusty, musty/earthy, pungent, acid,
      smoky, woody, burnt, ashy, cedar, creosote or petroleum-like collectively
      imparted smoked aroma. Most of the phenolic compounds were described as having
      smoky characteristics at low concentrations, generally at 1 and 10 ppm, except
      3,4-dimethylphenol at 5000 ppm. 2,6-Dimethylphenol was not associated with smoky
      characteristics. This research is the first to evaluate a set of phenolic
      compounds for their sensory characteristics using a professionally developed set
      of sensory attributes.

PMID- 29597300
TI  - Polymer-Mediated Delivery of siRNAs to Hepatocellular Carcinoma: Variables
      Affecting Specificity and Effectiveness.
AB  - Despite the advances in anticancer therapies, their effectiveness for many human
      tumors is still far from being optimal. Significant improvements in treatment
      efficacy can come from the enhancement of drug specificity. This goal may be
      achieved by combining the use of therapeutic molecules with tumor specific
      effects and delivery carriers with tumor targeting ability. In this regard,
      nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs),
      are attractive molecules due to the possibility to be engineered to target
      specific tumor genes. On the other hand, polymeric-based delivery systems are
      emerging as versatile carriers to generate tumor-targeted delivery systems. Here
      we will focus on the most recent findings in the selection of siRNA/polymeric
      targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for
      which currently available therapeutic approaches are poorly effective. In
      addition, we will discuss the most attracting and, in our opinion, promising
      siRNA-polymer combinations for HCC in relation to the biological features of HCC
      tissue. Attention will be also put on the mathematical description of the
      mechanisms ruling siRNA-carrier delivery, this being an important aspect to
      improve effectiveness reducing the experimental work.

PMID- 29597304
TI  - New Eudesmane-Type Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus
      Penicillium sp. J-54.
AB  - Four new eudesmane-type sesquiterpenoids, penicieudesmol A-D (1-4), were isolated
      from the fermentation broth of the mangrove-derived endophytic fungus Penicillium
      sp. J-54. Their structures were determined by spectroscopic methods, the in situ
      dimolybdenum CD method, and modified Mosher's method. The bioassays results
      showed that 2 exhibited weak cytotoxicity against K-562 cells.

PMID- 29597305
TI  - Effects of Consuming a Low Dose of Alcohol with Mixers Containing Carbohydrate or
      Artificial Sweetener on Simulated Driving Performance.
AB  - The Australian National Drug and Alcohol Research Centre (NDARC) devised gender
      based drinking recommendations to ensure blood or equivalized breath alcohol
      concentrations (BrAC) remain <0.050%. However, these may be inappropriate for
      individuals consuming alcohol without carbohydrate (CHO), which results in higher
      BrACs. This study investigated the effects of ingesting alcohol with and without
      CHO on BrACs and simulated driving performance. Thirty-two participants (16
      males; age: 23 +/- 6 years) completed two randomized single-blinded trials.
      Participants performed a baseline drive (Drive 1), then an experimental drive
      (Drive 2), following alcohol consumption (males: 20 g; females: 10 g). Alcoholic
      beverages contained either 25 g sucrose or aspartame (AS). Driving performance
      was assessed using lateral control (standard deviation of lane position [SDLP]
      and number of lane departures) and risk-taking (number of overtaking maneuvers
      and maximum overtaking speed). BrAC and subjective ratings (e.g., intoxication)
      were also assessed. BrAC was significantly lower as Drive 2 commenced with CHO
      compared to AS (0.022 +/- 0.008% vs. 0.030 +/- 0.011%). Two males provided BrACs
      >0.050% with AS. Neither beverage influenced changes to simulated driving
      performance. Ingesting alcohol in quantities advised by the NDARC results in no
      detectable simulated driving impairment. However, the likelihood of exceeding the
      legal drink-driving BrAC is increased when alcohol is consumed with artificially
      sweetened mixers.

PMID- 29597307
TI  - Factors Associated with High Live Release for Dogs at a Large, Open-Admission,
      Municipal Shelter.
AB  - Better understanding of factors contributing to live release (rehoming) may help
      shelters improve outcomes. In this cross-sectional, exploratory, non
      interventional study, data for all intakes (n = 21,409) for dogs eligible for
      rehoming from 1 January 2015 to 31 December 2016 are analyzed to identify such
      factors. Live release was >88%. A total of 1510 (7.1%) dogs interacted with the
      foster care system, 98.9% of whom had live release. Foster care increased the
      odds of live release by about five-fold for all dogs (odds ratio (OR) 5.30 (95%
      confidence interval (CI): 3.13; 8.97), p < 0.001) and by >20-fold for adult dogs
      (OR 22.2 (95% CI: 5.48; 90.2), p < 0.001) compared to first-time owner
      surrendered dogs. Dogs returned from foster care had a 70% reduction in health
      concerns, as judged by intake staff, compared with dogs sent to foster. In
      addition to saving 2882 lives, the rescue network utilized by this shelter was
      estimated as having reduced in-shelter care needs by 13,409 animal care-days over
      two years. Dogs returned from adoption also had increased odds of live release
      (OR 4.74 (95% CI: 3.02; 7.44), p < 0.0001). Nearly a third (29.6%) of dogs
      originally brought in by owners for euthanasia were determined to be potentially
      savable, and a fifth of the original group (21.1%) were ultimately placed. Less
      than 4% of dogs presented with behavioral concerns at intake. It remains to be
      determined whether other large, open intake shelters performing animal control
      can replicate these results.

PMID- 29597306
TI  - Biocompatibility of Gd-Loaded Chitosan-Hyaluronic Acid Nanogels as Contrast
      Agents for Magnetic Resonance Cancer Imaging.
AB  - Although the research on nanogels incorporating Gd chelates for theranostic
      applications has grown exponentially in recent years, knowledge about their
      biocompatibility is limited. We compared the biocompatibility of Gd-loaded
      hyaluronic acid-chitosan-based nanogels (GdCA?CS-TPP/HA) with two chitosan
      concentrations (2.5 and 1.5 mg.mL-1 respectively) using SVEC4-10 murine lymph
      node endothelial cells. The sulforhodamine B method and released lactate
      dehydrogenase (LDH) activity were used as cell viability tests. Reactive oxygen
      species (ROS), reduced glutathione (GSH) and malondialdehyde (MDA) were measured
      by spectrophotometric and fluorimetric methods. Nrf-2 protein expression was
      evaluated by Western blot analysis and genotoxicity by alkaline comet assay.
      After 24 h, the cells viability was not affected by all types and doses of
      nanogels. The increase of ROS induced a low decrease of GSH concentration and a
      time-dependent raise of MDA one was produced by citric GdDOTA?CS-TPP/HA with a
      chitosan concentration of 1.5 mg.mL-1, at the highest dose applied. None of the
      tested nanogels induced changes in Nrf-2 protein expression. A slight but
      significant genotoxic effect was caused only by citric GdDOTA?CS-TPP/HA where CS
      concentration was 1.5 mg.mL-1. Our results showed a better biocompatibility with
      lymph node endothelial cells for Gd-loaded hyaluronic acid-chitosan based
      nanogels with a concentration in chitosan of 2.5 mg.mL-1.

PMID- 29597308
TI  - 'Obesogenic' School Food Environments? An Urban Case Study in The Netherlands.
AB  - (1) Background: This study aimed to explore and define socio-economic (SES)
      differences in urban school food environments in The Netherlands. (2) Methods:
      Retail food outlets, ready-to-eat products, in-store food promotions and food
      advertisements in public space were determined within 400 m walking distance of
      all secondary schools in the 4th largest city of The Netherlands. Fisher's exact
      tests were conducted. (3) Results: In total, 115 retail outlets sold ready-to-eat
      food and drink products during school hours. Fast food outlets were more often in
      the vicinity of schools in lower SES (28.6%) than in higher SES areas (11.5%). In
      general, unhealthy options (e.g., fried snacks, sugar-sweetened beverages (SSB))
      were more often for sale, in-store promoted or advertised in comparison with
      healthy options (e.g., fruit, vegetables, bottled water). Sport/energy drinks
      were more often for sale, and fried snacks/fries, hamburgers/kebab and SSB were
      more often promoted or advertised in lower SES areas than in higher SES-areas.
      (4) Conclusion: In general, unhealthy food options were more often presented than
      the healthy options, but only a few SES differences were observed. The results,
      however, imply that efforts in all school areas are needed to make the healthy
      option the default option during school time.

PMID- 29597309
TI  - Emerging Non-Canonical Functions and Regulation of p53.
AB  - The tumor suppressor p53 induces cell cycle arrest and/or apoptosis by
      transactivating numerous downstream target genes and also translocating to the
      mitochondrial outer membrane.

PMID- 29597310
TI  - Optimization and Characterization of Preceramic Inks for Direct Ink Writing of
      Ceramic Matrix Composite Structures.
AB  - In a previous work, an ink based on a preceramic polymer, SiC fillers, and
      chopped carbon fibers was proposed for the production of Ceramic Matrix Composite
      (CMC) structures by Direct Ink Writing (DIW) and subsequent pyrolysis. Thanks to
      the shear stresses generated at the nozzle tip during extrusion, carbon fibers
      can be aligned along the printing direction. Fumed silica was added to the ink in
      order to enhance its rheological properties; however, the printed structures
      still showed some deformation in the Z direction. In this work, a second ink was
      successfully developed to limit deformation and at the same time avoid the
      addition of fumed silica, which limited the potential temperature of application
      of the composites. Instead, the positive role of the preceramic polymer on the
      ink rheology was exploited by increasing its concentration in the ink.
      Rheological characterization carried out on both inks confirmed that they
      possessed Bingham shear thinning behavior and fast viscosity recovery. Single
      filaments with different diameters (~310 um and ~460 um) were produced with the
      latter ink by DIW and subsequent pyrolysis. Tested under a four-point flexural
      test, the filaments showed a mean flexural strength above 30 MPa, graceful
      failure, and fiber pull-out. The results of this work suggest that CMC components
      can effectively be fabricated via DIW of a preceramic ink with embedded short
      fibers; the preceramic polymer is able to provide the desired rheology for the
      process and to develop a dense matrix capable of incorporating both fibers and
      ceramic particles, whereas the fibers addition contributes to an increase of the
      fracture toughness of the material and to the development of a graceful failure
      mode.

PMID- 29597311
TI  - Synthesis and Characterization of Sulfonated Graphene Oxide Reinforced Sulfonated
      Poly (Ether Ether Ketone) (SPEEK) Composites for Proton Exchange Membrane
      Materials.
AB  - As a clean energy utilization device, full cell is gaining more and more
      attention. Proton exchange membrane (PEM) is a key component of the full cell.
      The commercial-sulfonated, tetrafluoroethylene-based fluoropolymer-copolymer
      (Nafion) membrane exhibits excellent proton conductivity under a fully humidified
      environment. However, it also has some disadvantages in practice, such as high
      fuel permeability, a complex synthesis process, and high cost. To overcome these
      disadvantages, a low-cost and novel membrane was developed. The sulfonated poly
      (ether ether ketone) (SPEEK) was selected as the base material of the proton
      exchange membrane. Sulfonated graphene (SG) was cross-linked with SPEEK through
      the elimination reaction of hydrogen bonds. It was found that the sulfonic acid
      groups and hydrophilic oxygen groups increased obviously in the resultant
      membrane. Compared with the pure SPEEK membrane, the SG-reinforced membrane
      exhibited better proton conductivity and methanol permeability prevention. The
      results indicate that the SG/SPEEK could be applied as a new proton exchange
      membrane in fuel cells.

PMID- 29597312
TI  - Characterization of Wood Derived Hierarchical Cellulose Scaffolds for
      Multifunctional Applications.
AB  - Functional materials of high porosity and hierarchical structure, based on
      renewable building blocks, are highly demanded for material applications. In this
      regard, substantial progress has been made by functionalizing micro- and nano
      sized cellulose followed by its reassembly via bottom-up approaches. However,
      bottom-up assembly processes are still limited in terms of upscaling and the
      utilization of these building blocks presupposes the disassembly of the plant
      feedstock inherit hierarchical cellulose scaffold. To maintain the three
      dimensional structure, delignification processes from pulp and paper production
      were recently adapted for the treatment of bulk wood. Yet, a detailed chemical
      analysis and the determination of macroscopic swelling/shrinkage parameters for
      the scaffolds, necessary for a systematic design of cellulose scaffold based
      materials, are still missing. Here, acidic bleaching and soda pulping were used
      for producing cellulose scaffolds, for functional materials under retention of
      their inherent hierarchical structure. Spatially resolved chemical investigations
      on thin sections by Raman microscopy provided detailed information on the induced
      alterations at the cell wall level, revealing significant differences in
      dependence of the chemistry of the pre-treatment. An adaption to bulk wood
      samples proved the applicability of these treatments at larger scales and
      volumetric alterations at different atmospheric conditions indicated the effect
      of the altered porosity of the scaffolds on their hygroscopic behaviour.

PMID- 29597313
TI  - Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced
      MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity.
AB  - A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited
      photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) identified in the
      hydrolysate had a high hydroxyl radical scavenging activity. In this study,
      activities of LSGYGP were further evaluated using ultraviolet B (UVB)-induced
      mouse embryonic fibroblasts (MEFs). UVB irradiation significantly increased the
      intercellular reactive oxygen species (ROS) production and matrix
      metalloproteinases (MMPs) activities and decreased the content of collagen in
      MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs.
      Meanwhile, the decrease of superoxide dismutase (SOD) activity and the increase
      of malondiaidehyde (MDA) content were inhibited by LSGYGP. LSGYGP reduced MMP-1
      and MMP-9 activities in a dose-dependent manner. Molecular docking simulation
      indicated that LSGYGP inhibited MMPs activities by docking the active sites of
      MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular
      phosphorylation of UVB-induced the mitogen-activated protein kinase pathway.
      LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by
      inhibiting oxidative stress and regulating MMPs activities.

PMID- 29597314
TI  - Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical
      Approach.
AB  - Swelling of mitochondria plays an important role in the pathogenesis of human
      diseases by stimulating mitochondria-mediated cell death through apoptosis,
      necrosis, and autophagy. Changes in the permeability of the inner mitochondrial
      membrane (IMM) of ions and other substances induce an increase in the colloid
      osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling
      is important for simulation and prediction of in vivo events in the cell during
      oxidative and energy stress. In the present study, we developed a computational
      model that describes the mechanism of mitochondrial swelling based on osmosis,
      the rigidity of the IMM, and dynamics of ionic/neutral species. The model
      describes a new biophysical approach to swelling dynamics, where osmotic pressure
      created in the matrix is compensated for by the rigidity of the IMM, i.e.,
      osmotic pressure induces membrane deformation, which compensates for the osmotic
      pressure effect. Thus, the effect is linear and reversible at small membrane
      deformations, allowing the membrane to restore its normal form. On the other
      hand, the membrane rigidity drops to zero at large deformations, and the swelling
      becomes irreversible. As a result, an increased number of dysfunctional
      mitochondria can activate mitophagy and initiate cell death. Numerical modeling
      analysis produced results that reasonably describe the experimental data reported
      earlier.

PMID- 29597315
TI  - Strategies on Nanodiagnostics and Nanotherapies of the Three Common Cancers.
AB  - The emergence of nanomedicine has enriched the knowledge and strategies of
      treating diseases, and especially some incurable diseases, such as cancers,
      acquired immune deficiency syndrome (AIDS), and neurodegenerative diseases. The
      application of nanoparticles in medicine is in the core of nanomedicine.
      Nanoparticles can be used in drug delivery for improving the uptake of poorly
      soluble drugs, targeted delivery to a specific site, and drug bioavailability.
      Early diagnosis of and targeted therapies for cancers can significantly improve
      patients' quality of life and extend patients' lives. The advantages of
      nanoparticles have given them a progressively important role in the nanodiagnosis
      and nanotherapy of common cancers. To provide a reference for the further
      application of nanoparticles, this review focuses on the recent development and
      application of nanoparticles in the early diagnosis and treatment of the three
      common cancers (lung cancer, liver cancer, and breast cancer) by using quantum
      dots, magnetic nanoparticles, and gold nanoparticles.

PMID- 29597316
TI  - Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System.
AB  - In the synthesis of five-membered heterocycles by the annulation of epoxides with
      heterocumulenes such as carbon dioxide and isocyanates, we developed the indium
      tin catalytic system and synthesized various cyclic adducts including novel types
      products under mild reaction conditions.

PMID- 29597317
TI  - Contributions of Bioactive Molecules in Stem Cell-Based Periodontal Regeneration.
AB  - Periodontal disease is a widespread disease, which without proper treatment, may
      lead to tooth loss in adults. Because stem cells from the inflammatory
      microenvironment created by periodontal disease exhibit impaired regeneration
      potential even under favorable conditions, it is difficult to obtain satisfactory
      therapeutic outcomes using traditional treatments, which only focus on the
      control of inflammation. Therefore, a new stem cell-based therapy known as cell
      aggregates/cell sheets technology has emerged. This approach provides sufficient
      numbers of stem cells with high viability for treating the defective site and
      offers new hope in the field of periodontal regeneration. However, it is not
      sufficient for regenerating periodontal tissues by delivering cell
      aggregates/cell sheets to the impaired microenvironment in order to suppress the
      function of resident cells. In the present review, we summarize some promising
      bioactive molecules that act as cellular signals, which recreate a favorable
      microenvironment for tissue regeneration, recruit endogenous cells into the
      defective site and enhance the viability of exogenous cells.

PMID- 29597319
TI  - Beliefs about Vaccinations: Comparing a Sample from a Medical School to That from
      the General Population.
AB  - The current study compares health care professionals' beliefs about vaccination
      statements with the beliefs of a sample of individuals from the general
      population. Students and faculty within a medical school (n = 58) and a sample
      from the general population in the United States (n = 177) were surveyed
      regarding their beliefs about vaccinations. Participants evaluated statements
      about vaccinations (both supporting and opposing), and indicated whether they
      thought the general population would agree with them. Overall, it was found that
      subjects in both populations agreed with statements supporting vaccination over
      opposing statements, but the general population was more likely to categorize the
      supporting statements as beliefs rather than facts. Additionally, there was
      little consensus within each population as to which statements were considered
      facts versus beliefs. Both groups underestimated the number of people that would
      agree with them; however, the medical affiliates showed the effect significantly
      more. Implications for medical education and health communication are discussed.

PMID- 29597318
TI  - Can a Red Wood-Ant Nest Be Associated with Fault-Related CH4 Micro-Seepage? A
      Case Study from Continuous Short-Term In-Situ Sampling.
AB  - We measured methane (CH4) and stable carbon isotope of methane (delta13C-CH4)
      concentrations in ambient air and within a red wood-ant (RWA; Formica polyctena)
      nest in the Neuwied Basin (Germany) using high-resolution in-situ sampling to
      detect microbial, thermogenic, and abiotic fault-related micro-seepage of CH4.
      Methane degassing from RWA nests was not synchronized with earth tides, nor was
      it influenced by micro-earthquake degassing or concomitantly measured RWA
      activity. Two delta13C-CH4 signatures were identified in nest gas: -690/00 and 
      370/00. The lower peak was attributed to microbial decomposition of organic
      matter within the RWA nest, in line with previous observations that RWA nests are
      hot-spots of microbial CH4. The higher peak has not been reported in previous
      studies. We attribute this peak to fault-related CH4 emissions moving via fault
      networks into the RWA nest, which could originate either from thermogenic or
      abiotic CH4 formation. Sources of these micro-seepages could be Devonian schists,
      iron-bearing "Klerf Schichten", or overlapping micro-seepage of magmatic CH4 from
      the Eifel plume. Given the abundance of RWA nests on the landscape, their role as
      sources of microbial CH4 and biological indicators for abiotically-derived CH4
      should be included in estimation of methane emissions that are contributing to
      climatic change.

PMID- 29597320
TI  - Water Quality in Surface Water: A Preliminary Assessment of Heavy Metal
      Contamination of the Mashavera River, Georgia.
AB  - Water quality contamination by heavy metal pollution has severe effects on public
      health. In the Mashavera River Basin, an important agricultural area for the
      national food system in Georgia (e.g., vegetable, dairy and wine production),
      water contamination has multiple influences on the regional and country-wide
      health. With new industrial activities in the region, sediment extraction, and
      discharge of untreated wastewater into the river, its tributaries and irrigation
      canals, a comprehensive study of water quality was greatly needed. This study
      examined sediment and water samples from 17 sampling sites in the Mashavera River
      Basin during the high and low precipitation seasons. The results were
      characterized utilizing the Geo-accumulation Index (Igeo), Enrichment Factor
      (EF), Pollution Load index (PLI), Contamination Factor (CF) and Metal Index (MI).
      According to the CFs, Cu > Cd > Zn > Pb > Fe > Mn > Ni > Cr > Hg is the
      descending order for the content of all observed heavy metals in sediments
      collected in both seasons. Fe and As were additionally examined in water samples.
      Overall, As, Cd and Pb, all highly toxic elements, were found in high
      concentrations in downstream sample sites. According to these results,
      comprehensive monitoring with narrow intervals between sampling dates, more
      sample sites along all waterways, and proximate observation of multiple trace
      metal elements are highly recommended. Moreover, as the part of the water quality
      governance system, an immediate and sustainable collective action by all
      stakeholders to control the pollution level is highly recommended, as this issue
      is linked to the security of the national food system and poses a local public
      health risk.

PMID- 29597321
TI  - Ectopic Overexpression of a Novel R2R3-MYB, NtMYB2 from Chinese Narcissus
      Represses Anthocyanin Biosynthesis in Tobacco.
AB  - R2R3 MYB transcription factors play key functions in the regulation of secondary
      metabolites. In the present study, a R2R3 MYB transcriptional factor NtMYB2 was
      identified from Chinese narcissus (Narcissus tazetta L. var. Chinensis Roem) and
      functionally characterized. NtMYB2 belongs to subgroup 4 of the R2R3 MYB
      transcription factor family that are related to repressor MYBs involved in the
      regulation of anthocyanin and flavonoids. Transient expression confirmed that
      NtMYB2 strongly reduced the red pigmentation induced by MYB- anthocyanin
      activators in agro-infiltrated tobacco leaves. Ectopic expression of NtMYB2 in
      tobacco significantly reduced the pigmentation and altered the floral phenotypes
      in transgenic tobacco flowers. Gene expression analysis suggested that NtMYB2
      repressed the transcript levels of structural genes involved in anthocyanin
      biosynthesis pathway, especially the UFGT gene. NtMYB2 gene is expressed in all
      examined narcissus tissues; the levels of transcription in petals and corona is
      higher than other tissues and the transcription level at the bud stage was
      highest. These results show that NtMYB2 is involved in the regulation of
      anthocyanin biosynthesis pathway and may act as a repressor by down regulating
      the transcripts of key enzyme genes in Chinese narcissus.

PMID- 29597323
TI  - Sparse Unorganized Point Cloud Based Relative Pose Estimation for Uncooperative
      Space Target.
AB  - This paper proposes an autonomous algorithm to determine the relative pose
      between the chaser spacecraft and the uncooperative space target, which is
      essential in advanced space applications, e.g., on-orbit serving missions. The
      proposed method, named Congruent Tetrahedron Align (CTA) algorithm, uses the very
      sparse unorganized 3D point cloud acquired by a LIDAR sensor, and does not
      require any prior pose information. The core of the method is to determine the
      relative pose by looking for the congruent tetrahedron in scanning point cloud
      and model point cloud on the basis of its known model. The two-level index hash
      table is built for speeding up the search speed. In addition, the Iterative
      Closest Point (ICP) algorithm is used for pose tracking after CTA. In order to
      evaluate the method in arbitrary initial attitude, a simulated system is
      presented. Specifically, the performance of the proposed method to provide the
      initial pose needed for the tracking algorithm is demonstrated, as well as their
      robustness against noise. Finally, a field experiment is conducted and the
      results demonstrated the effectiveness of the proposed method.

PMID- 29597322
TI  - Aged (Black) versus Raw Garlic against Ischemia/Reperfusion-Induced Cardiac
      Complications.
AB  - Recent evidence from studies suggests that aged black garlic also has an effect
      on health. The major aim of the present study is to compare the effect of raw and
      aged black garlic on postischemic cardiac recovery. Male Sprague Dawley rats were
      randomly divided into three groups. Animals of the first group were fed with raw
      garlic, animals of the second group received aged black garlic, while the third
      group served as vehicle-treated controls. Upon conclusion of the treatment,
      isolated hearts were undertaken to ischemia/reperfusion. Heart function and
      infarct size were measured and the level of HO-1 and iNOS were studied. Superior
      postischemic cardiac function and reduced infarct size in both garlic treated
      groups compared to the drug-free control group, indicated cardioprotective
      effects. However, no significant differences between the garlic treated groups
      were observed. Western blot analysis revealed that raw garlic enhanced the level
      of HO-1 before ischemia, while in ischemic samples, we found elevated HO-1
      expression in both garlic treated groups. The level of iNOS was the same before
      ischemia in all groups, however, a markedly reduced iNOS level in
      ischemic/reperfused hearts originating from control and raw garlic treated
      animals was observed. Samples from aged black garlic treated animals demonstrated
      that the level of iNOS was not significantly reduced after ischemia/reperfusion.
      Taken together these results indicate that not only raw but also aged black
      garlic possess a cardioprotective effect.

PMID- 29597324
TI  - Single-Kernel FT-NIR Spectroscopy for Detecting Supersweet Corn (Zea mays L.
      Saccharata Sturt) Seed Viability with Multivariate Data Analysis.
AB  - The viability and vigor of crop seeds are crucial indicators for evaluating seed
      quality, and high-quality seeds can increase agricultural yield. The conventional
      methods for assessing seed viability are time consuming, destructive, and labor
      intensive. Therefore, a rapid and nondestructive technique for testing seed
      viability has great potential benefits for agriculture. In this study, single
      kernel Fourier transform near-infrared (FT-NIR) spectroscopy with a wavelength
      range of 1000-2500 nm was used to distinguish viable and nonviable supersweet
      corn seeds. Various preprocessing algorithms coupled with partial least squares
      discriminant analysis (PLS-DA) were implemented to test the performance of
      classification models. The FT-NIR spectroscopy technique successfully
      differentiated viable seeds from seeds that were nonviable due to overheating or
      artificial aging. Correct classification rates for both heat-damaged kernels and
      artificially aged kernels reached 98.0%. The comprehensive model could also
      attain an accuracy of 98.7% when combining heat-damaged samples and artificially
      aged samples into one category. Overall, the FT-NIR technique with multivariate
      data analysis methods showed great potential capacity in rapidly and
      nondestructively detecting seed viability in supersweet corn.

PMID- 29597325
TI  - Diaphragm-Free Fiber-Optic Fabry-Perot Interferometric Gas Pressure Sensor for
      High Temperature Application.
AB  - A diaphragm-free fiber-optic Fabry-Perot (FP) interferometric gas pressure sensor
      is designed and experimentally verified in this paper. The FP cavity was
      fabricated by inserting a well-cut fiber Bragg grating (FBG) and hollow silica
      tube (HST) from both sides into a silica casing. The FP cavity length between the
      ends of the SMF and HST changes with the gas density. Using temperature
      decoupling method to improve the accuracy of the pressure sensor in high
      temperature environments. An experimental system for measuring the pressure under
      different temperatures was established to verify the performance of the sensor.
      The pressure sensitivity of the FP gas pressure sensor is 4.28 nm/MPa with a high
      linear pressure response over the range of 0.1-0.7 MPa, and the temperature
      sensitivity is 14.8 pm/ degrees C under the range of 20-800  degrees C. The
      sensor has less than 1.5% non-linearity at different temperatures by using
      temperature decoupling method. The simple fabrication and low-cost will help
      sensor to maintain the excellent features required by pressure measurement in
      high temperature applications.

PMID- 29597326
TI  - Experimental Study of the Oriented Immobilization of Antibodies on Photonic
      Sensing Structures by Using Protein A as an Intermediate Layer.
AB  - A proper antibody immobilization on a biosensor is a crucial step in order to
      obtain a high sensitivity to be able to detect low target analyte concentrations.
      In this paper, we present an experimental study of the immobilization process of
      antibodies as bioreceptors on a photonic ring resonator sensor. A protein A
      intermediate layer was created on the sensor surface in order to obtain an
      oriented immobilization of the antibodies, which enhances the interaction with
      the target antigens to be detected. The anti-bovine serum albumin (antiBSA)
      bovine serum albumin (BSA) pair was used as a model for our study. An opto
      fluidic setup was developed in order to flow the different reagents and,
      simultaneously, to monitor in real-time the spectral response of the photonic
      sensing structure. The antiBSA immobilization and the BSA detection, their
      repeatability, and specificity were studied in different conditions of the sensor
      surface. Finally, an experimental limit of detection for BSA recognition of only
      1 ng/mL was obtained.

PMID- 29597327
TI  - A Simultaneous and Continuous Excitation Method for High-Speed Electrical
      Impedance Tomography with Reduced Transients and Noise Sensitivity.
AB  - This paper presents a concept for soft field tomographic scan of all the
      projections of electromagnetic waves emanating from an array of electrodes.
      Instead of the sequential excitation of all pairs of electrodes in the list of
      all projections, the new method present here consists of a single and continuous
      excitation. This excitation signal is the linear combination of the excitation
      signals in the projection set at different AC frequencies. The response to a
      given projection is discriminated by selecting the corresponding AC frequency
      component in the signal spectra of the digitally demodulated signals. The main
      advantage of this method is the suppression of transients after each projection,
      which is particularly problematic in electrical impedance tomography due to
      contact impedance phenomena and skin effect. The second benefit over the
      sequential scan method is the increased number of samples for each measurement
      for reduced noise sensitivity with digital demodulation. The third benefit is the
      increased temporal resolution in high-speed applications. The main drawback is
      the increased number of signal sources required (one per electrode). This paper
      focuses on electrical impedance tomography, based on earlier work by the authors.
      An experimental proof-of-concept using a simple 4-electrodes electrical impedance
      tomographic system is presented using simulations and laboratory data. The method
      presented here may be extended to other modalities (ultrasonic, microwave,
      optical, etc.).

PMID- 29597328
TI  - Assembly of the Boechera retrofracta Genome and Evolutionary Analysis of Apomixis
      Associated Genes.
AB  - Closely related to the model plant Arabidopsis thaliana, the genus Boechera is
      known to contain both sexual and apomictic species or accessions. Boechera
      retrofracta is a diploid sexually reproducing species and is thought to be an
      ancestral parent species of apomictic species. Here we report the de novo
      assembly of the B. retrofracta genome using short Illumina and Roche reads from 1
      paired-end and 3 mate pair libraries. The distribution of 23-mers from the paired
      end library has indicated a low level of heterozygosity and the presence of
      detectable duplications and triplications. The genome size was estimated to be
      equal 227 Mb. N50 of the assembled scaffolds was 2.3 Mb. Using a hybrid approach
      that combines homology-based and de novo methods 27,048 protein-coding genes were
      predicted. Also repeats, transfer RNA (tRNA) and ribosomal RNA (rRNA) genes were
      annotated. Finally, genes of B. retrofracta and 6 other Brassicaceae species were
      used for phylogenetic tree reconstruction. In addition, we explored the histidine
      exonuclease APOLLO locus, related to apomixis in Boechera, and proposed model of
      its evolution through the series of duplications. An assembled genome of B.
      retrofracta will help in the challenging assembly of the highly heterozygous
      genomes of hybrid apomictic species.

PMID- 29597329
TI  - The Human Tyrosyl-DNA Phosphodiesterase 1 (hTdp1) Inhibitor NSC120686 as an
      Exploratory Tool to Investigate Plant Tdp1 Genes.
AB  - The hTdp1 (human tyrosyl-DNA phosphodiesterase 1) inhibitor NSC120686 has been
      used, along with topoisomerase inhibitors, as a pharmacophoric model to restrain
      the Tdp1 activity as part of a synergistic treatment for cancer. While this
      compound has an end-point application in medical research, in plants, its
      application has not been considered so far. The originality of our study consists
      in the use of hTdp1 inhibitor in Medicago truncatula cells, which, unlike human
      cells, contain two Tdp1 genes. Hence, the purpose of this study was to test the
      hTdp1 inhibitor NSC120686 as an exploratory tool to investigate the plant Tdp1
      genes, since their characterization is still in incipient phases. To do so, M.
      truncatula calli were exposed to increasing (75, 150, 300 MUM) concentrations of
      NSC120686. The levels of cell mortality and DNA damage, measured via diffusion
      assay and comet assay, respectively, were significantly increased when the
      highest doses were used, indicative of a cytotoxic and genotoxic threshold. In
      addition, the NSC120686-treated calli and untreated MtTdp1alpha-depleted calli
      shared a similar response in terms of programmed cell death (PCD)/necrosis and
      DNA damage. Interestingly, the expression profiles of MtTdp1alpha and MtTdp1beta
      genes were differently affected by the NSC120686 treatment, as MtTdp1alpha was
      upregulated while MtTdp1beta was downregulated. The NSC120686 treatment affected
      not only the MtTdp1 genes but also other genes with roles in alternative DNA
      repair pathways. Since the expression patterns of these genes were different than
      what was observed in the MtTdp1alpha-depleted plants, it could be hypothesized
      that the NSC120686 treatment exerts a different influence compared to that
      resulting from the lack of the MtTdp1alpha gene function.

PMID- 29597330
TI  - Investigation of Absorption Routes of Meloxicam and Its Salt Form from Intranasal
      Delivery Systems.
AB  - The aim of this article was to study the trans-epithelial absorption to reach the
      blood and to target the brain by axonal transport using nasal formulations with
      nanonized meloxicam (nano MEL spray) and its salt form known as meloxicam
      potassium monohydrate (MELP spray). The physicochemical properties and the
      mucoadhesivity of nasal formulations were controlled. In vitro and in vivo
      studies were carried out. These forms were first investigated in "nose-to-brain"
      relation. It was found that the in vitro study and in vivo study did not show any
      significant correlation. In vitro experiments demonstrated faster dissolution
      rate and higher diffusion of MELP from the spray compared with the nano MEL
      spray. The administration of the nano MEL spray resulted in faster absorption and
      constant plasma concentration of the drug after five minutes of administration as
      compared to MELP. The axonal transport of the drug was justified. MEL appeared in
      the brain tissues after the first five minutes of administration in the case of
      both spray forms, but its amount was too small in comparison with the total
      plasma concentration. The application of the nano MEL spray resulted in the same
      AUC in the brain as the intravenous injection. The "nose-to-blood" results
      predicted the nasal applicability of MEL and MELP in pain management. The "nose
      to-brain" pathway requires further study.

PMID- 29597331
TI  - A New FPGA Architecture of FAST and BRIEF Algorithm for On-Board Corner Detection
      and Matching.
AB  - Although some researchers have proposed the Field Programmable Gate Array (FPGA)
      architectures of Feature From Accelerated Segment Test (FAST) and Binary Robust
      Independent Elementary Features (BRIEF) algorithm, there is no consideration of
      image data storage in these traditional architectures that will result in no
      image data that can be reused by the follow-up algorithms. This paper proposes a
      new FPGA architecture that considers the reuse of sub-image data. In the proposed
      architecture, a remainder-based method is firstly designed for reading the sub
      image, a FAST detector and a BRIEF descriptor are combined for corner detection
      and matching. Six pairs of satellite images with different textures, which are
      located in the Mentougou district, Beijing, China, are used to evaluate the
      performance of the proposed architecture. The Modelsim simulation results found
      that: (i) the proposed architecture is effective for sub-image reading from DDR3
      at a minimum cost; (ii) the FPGA implementation is corrected and efficient for
      corner detection and matching, such as the average value of matching rate of
      natural areas and artificial areas are approximately 67% and 83%, respectively,
      which are close to PC's and the processing speed by FPGA is approximately 31 and
      2.5 times faster than those by PC processing and by GPU processing, respectively.

PMID- 29597332
TI  - Makaluvamine G from the Marine Sponge Zyzzia fuliginosa Inhibits Muscle nAChR by
      Binding at the Orthosteric and Allosteric Sites.
AB  - Diverse ligands of the muscle nicotinic acetylcholine receptor (nAChR) are used
      as muscle relaxants during surgery. Although a plethora of such molecules exists
      in the market, there is still a need for new drugs with rapid on/off-set,
      increased selectivity, and so forth. We found that pyrroloiminoquinone alkaloid
      Makaluvamine G (MG) inhibits several subtypes of nicotinic receptors and
      ionotropic gamma-aminobutiric acid receptors, showing a higher affinity and
      moderate selectivity toward muscle nAChR. The action of MG on the latter was
      studied by a combination of electrophysiology, radioligand assay, fluorescent
      microscopy, and computer modeling. MG reveals a combination of competitive and un
      competitive inhibition and caused an increase in the apparent desensitization
      rate of the murine muscle nAChR. Modeling ion channel kinetics provided evidence
      for MG binding in both orthosteric and allosteric sites. We also demonstrated
      that thealpha1 (G153S) mutant of the receptor, associated with the myasthenic
      syndrome, is more prone to inhibition by MG. Thus, MG appears to be a perspective
      hit molecule for the design of allosteric drugs targeting muscle nAChR,
      especially for treating slow-channel congenital myasthenic syndromes.

PMID- 29597333
TI  - From the Child's Word to Clinical Intervention: Novel, New, and Innovative
      Approaches to Symptoms in Pediatric Palliative Care.
AB  - Despite vast improvements in disease-based treatments, many children live with
      life-threatening disorders that cause distressing symptoms. These symptoms can be
      difficult to comprehensively assess and manage. Yet, frequent and accurate
      symptom reporting and expert treatment is critical to preserving a patient's
      physical, psychological, emotional, social, and existential heath. We describe
      emerging methods of symptom and health-related quality-of-life (HRQOL) assessment
      through patient-reported outcomes (PROs) tools now used in clinical practice and
      novel research studies. Computer-based and mobile apps can facilitate assessment
      of symptoms and HRQOL. These technologies can be used alone or combined with
      therapeutic strategies to improve symptoms and coping skills. We review
      technological advancements, including mobile apps and toys, that allow improved
      symptom reporting and management. Lastly, we explore the value of a pediatric
      palliative care interdisciplinary team and their role in assessing and managing
      distressing symptoms and minimizing suffering in both the child and family. These
      methods and tools highlight the way that novel, new, and innovative approaches to
      symptom assessment and management are changing the way that pediatrics and
      pediatric palliative care will be practiced in the future.

PMID- 29597334
TI  - Microglia after Seizures and in Epilepsy.
AB  - Microglia are the resident immune cells in the brain that constitute the brain's
      innate immune system. Recent studies have revealed various functions of microglia
      in the development and maintenance of the central nervous system (CNS) in both
      health and disease. However, the role of microglia in epilepsy remains largely
      undiscovered, partly because of the complex phenotypes of activated microglia.
      Activated microglia likely exert different effects on brain function depending on
      the phase of epileptogenesis. In this review, we mainly focus on the animal
      models of temporal lobe epilepsy (TLE) and discuss the proepileptic and
      antiepileptic roles of activated microglia in the epileptic brain. Specifically,
      we focus on the roles of microglia in the production of inflammatory cytokines,
      regulation of neurogenesis, and surveillance of the surrounding environment in
      epilepsy.

PMID- 29597335
TI  - Simian Varicella Virus Infects Enteric Neurons and alpha4beta7 Integrin
      Expressing Gut-Tropic T-Cells in Nonhuman Primates.
AB  - The pathogenesis of enteric zoster, a rare debilitating complication of
      reactivation of latent varicella-zoster virus (VZV) in the enteric nervous system
      (ENS), is largely unknown. Infection of monkeys with the closely related
      Varicellovirus simian varicella virus (SVV) mimics VZV disease in humans. In this
      study, we determined the applicability of the SVV nonhuman primate model to study
      Varicellovirus infection of the ENS. We confirmed VZV infection of the gut in
      latently infected adults and demonstrated that SVV DNA was similarly present in
      gut of monkeys latently infected with SVV using quantitative real-time PCR. In
      situ analyses showed that enteric neurons expressed SVV open reading frame (ORF)
      63 RNA, but not viral nucleocapsid proteins, suggestive of latent ENS infection.
      During primary infection, SVV-infected T-cells were detected in gut-draining
      mesenteric lymph nodes and located in close vicinity to enteric nerves in the
      gut. Furthermore, flow cytometric analysis of blood from acutely SVV-infected
      monkeys demonstrated that virus-infected T-cells expressed the gut-homing
      receptor alpha4beta7 integrin. Collectively, the data demonstrate that SVV
      infects ENS neurons during primary infection and supports the role of T-cells in
      virus dissemination to the gut. Because SVV reactivation can be experimentally
      induced, the SVV nonhuman primate model holds great potential to study the
      pathogenesis of enteric zoster.

PMID- 29597337
TI  - Behavioral Intervention in Adolescents Improves Bone Mass, Yet Lactose
      Maldigestion Is a Barrier.
AB  - Calcium intake during adolescence is important for attainment of peak bone mass.
      Lactose maldigestion is an autosomal recessive trait, leading to lower calcium
      intake. The Adequate Calcium Today study aimed to determine if a school-based
      targeted behavioral intervention over one year could improve calcium intake and
      bone mass in early adolescent girls. The school-randomized intervention was
      conducted at middle schools in six states over one school year. A total of 473
      girls aged 10-13 years were recruited for outcome assessments. Bone mineral
      content (BMC) was determined by dual energy X-ray absorptiometry. Dietary calcium
      intake was assessed with a semi-quantitative food frequency questionnaire.
      Baseline calcium intake and BMC were not significantly different between groups.
      After the intervention period, there were no differences in changes in calcium
      intake and BMC at any site between groups. An unanticipated outcome was a greater
      increase in spinal BMC among lactose digesters than lactose maldigesters in the
      intervention schools only (12 months) (6.9 +/- 0.3 g vs. 6.0 +/- 0.4 g, p = 0.03)
      and considering the entire study period (18 months) (9.9 +/- 0.4 vs. 8.7 +/- 0.5
      g, p < 0.01). Overall, no significant differences between the intervention and
      control schools were observed. However, lactose digesters who received the
      intervention program increased bone mass to a greater extent than lactose
      maldigesters.

PMID- 29597336
TI  - Comparative Evaluation of the Antioxidant and Anti-Alzheimer's Disease Potential
      of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling
      Studies.
AB  - The current study assesses the antioxidant effects of two similar isoflavonoids
      isolated from Pueraria lobata, coumestrol and puerarol, along with the
      cholinergic and amyloid-cascade pathways to mitigate Alzheimer's disease (AD).
      Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and
      peroxynitrite (ONOO-) scavenging ability further screened via ONOO--mediated
      nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and beta
      site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities
      were assessed together with docking and kinetic studies. Considering DPPH and
      ONOO- scavenging activity, coumestrol (EC50 values of 53.98 and 1.17 uM) was
      found to be more potent than puerarol (EC50 values of 82.55 and 6.99 uM) followed
      by dose dependent inhibition of ONOO--mediated nitrotyrosine. Coumestrol showed
      pronounced AChE and BChE activity with IC50 values of 42.33 and 24.64 uM,
      respectively, acting as a dual cholinesterase (ChE) inhibitor. Despite having
      weak ChE inhibitory activity, puerarol showed potent BACE1 inhibition (28.17 uM).
      Kinetic studies of coumestrol showed AChE and BChE inhibition in a competitive
      and mixed fashion, whereas puerarol showed mixed inhibition for BACE1. In
      addition, docking simulations demonstrated high affinity and tight binding
      capacity towards the active site of the enzymes. In summary, we undertook a
      comparative study of two similar isoflavonoids differing only by a single
      aliphatic side chain and demonstrated that antioxidant agents coumestrol and
      puerarol are promising, potentially complementary therapeutics for AD.

PMID- 29597338
TI  - Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans.
AB  - Paralytic shellfish poisoning (PSP) is caused by a group of marine toxins with
      saxitoxin (STX) as the reference compound. Symptoms in humans after consumption
      of contaminated shellfish vary from slight neurological and gastrointestinal
      effects to fatal respiratory paralysis. A systematic review was conducted to
      identify reported cases of human poisoning associated with the ingestion of
      shellfish contaminated with paralytic shellfish toxins (PSTs). Raw data were
      collected from 143 exposed individuals (113 with symptoms, 30 without symptoms)
      from 13 studies. Exposure estimates were based on mouse bioassays except in one
      study. A significant relationship between exposure to PSTs and severity of
      symptoms was established by ordinal modelling. The critical minimal dose with a
      probability higher than 10% of showing symptoms is 0.37 ug STX eq./kg b.w. This
      means that 10% of the individuals exposed to this dose would have symptoms
      (without considering the severity of the symptoms). This dose is four-fold lower
      than the lowest-observed-adverse-effect-level (LOAEL) established by the European
      Food Safety Authority (EFSA, 2009) in the region of 1.5 MUg STX eq./kg b.w. This
      work provides critical doses that could be used as point of departure to update
      the acute reference dose for STX. This is the first time a dose-symptoms model
      could be built for marine toxins using epidemiological data.

PMID- 29597339
TI  - omega-Methylsulfanylalkyl Glucosinolates: A General Synthetic Pathway.
AB  - A general pathway was devised to synthesize omega-methylsulfanylalkyl
      glucosinolates, which represent an important class of structurally homogeneous
      plant secondary metabolites. The required thiofunctionalized hydroximoyl
      chlorides were obtained from the corresponding alpha,omega-nitroalkyl
      methylsulfide precursors, involving as the key-step, a nitronate chlorination
      strategy. A coupling reaction with 1-thio-beta-d-glucopyranose, followed by O
      sulfation of the intermediate thiohydroximate and final deprotection of the sugar
      moiety afforded the target compounds.

PMID- 29597340
TI  - Alpha Particle Detection Using Alpha-Induced Air Radioluminescence: A Review and
      Future Prospects for Preliminary Radiological Characterisation for Nuclear
      Facilities Decommissioning.
AB  - The United Kingdom (UK) has a significant legacy of nuclear installations to be
      decommissioned over the next 100 years and a thorough characterisation is
      required prior to the development of a detailed decommissioning plan. Alpha
      radiation detection is notoriously time consuming and difficult to carry out due
      to the short range of alpha particles in air. Long-range detection of alpha
      particles is therefore highly desirable and this has been attempted through the
      detection of secondary effects from alpha radiation, most notably the air
      radioluminescence caused by ionisation. This paper evaluates alpha induced air
      radioluminescence detectors developed to date and looks at their potential to
      develop a stand-off, alpha radiation detector which can be used in the nuclear
      decommissioning field in daylight conditions to detect alpha contaminated
      materials.

PMID- 29597341
TI  - Parents' Experience and Views of Vaccinating Their Child against Influenza at
      Primary School and at the General Practice.
AB  - The purpose of this study was to gain an in-depth understanding of parents'
      experience and views of vaccinating their four to six-year-old child against
      influenza at school and at the general practice (GP). A cross-sectional
      qualitative study was conducted between March-June 2016 with parents of children
      in Reception and Year 1 in four randomly selected schools in Bury,
      Leicestershire, and Surrey, England. Twenty-five outreach forms were completed
      and returned, and seven interviews were conducted. Interview transcripts were
      coded by theme in NVivo (version 11, QSR International Pty Ltd., Melbourne,
      Australia). The primary reason parents gave for vaccinating their child was to
      prevent their child from contracting influenza. Parents' perceived benefits of
      vaccinating in schools were to avoid the inconvenience of having to take their
      child to the GP, and that their child would behave better at school. Parents
      viewed that accompanying their child for the vaccination at school would
      undermine the convenience and peer-pressure advantages of the school as a venue.
      No parents expressed concern about their child being too young to be vaccinated
      in school. This research suggests that the school is a desirable venue for
      childhood influenza vaccination, both from the parents' view and given that
      influenza vaccination coverage is higher when delivered through schools than GPs.

PMID- 29597342
TI  - Study on Betalains in Celosia cristata Linn. Callus Culture and Identification of
      New Malonylated Amaranthins.
AB  - Betacyanins and betaxanthins were characterized and determined in an intensely
      pigmented red-colored callus culture of Celosia cristata L. (Amaranthaceae). A
      new malonyl derivative, 6'- O-malonyl-amaranthin (celoscristatin) was isolated
      and identified by spectroscopic and mass spectrometric techniques. Its
      stereoisomer, 4'- O-malonyl-amaranthin (celoscristatin acyl-migrated), as well as
      its 15 R diastereomer were also detected in the callus as a result of the malonyl
      group migration in celoscristatin/isoceloscristatin, respectively. Amaranthin
      occurs in the callus as the major betacyanin, followed by celoscristatin,
      betanin, phyllocactin, and other minor betacyanins. The effect of different
      carbon sources on the growth rates of the Celosia callus as well as on betalains
      profiles in the callus cultures was studied. High dopamine content in the callus
      culture was determined and compared with the content in C. cristata
      inflorescences. The dopamine-based betalain (miraxanthin V) was detected as the
      main betaxanthin in the callus, however, at a concentration level much lower than
      that of the identified betacyanins. The studied callus culture of C. cristata can
      accumulate betalains in amounts which approach the quantities produced by most
      known high-yielding plant species.

PMID- 29597344
TI  - Rhabdopeptides from Xenorhabdus budapestensis SN84 and Their Nematicidal
      Activities against Meloidogyne incognita.
AB  - For decades, plant parasitic nematodes have caused serious damage to crop
      production. Most nematicides are banned because of their negative impacts on the
      environment and public health. The repeated application of the few commercially
      available nematicides has caused more incidences of nematicide resistance. To
      seek novel nematicides, seven linear peptides named rhabdopeptides I-O, 1-7, were
      isolated from culture broth of Xenorhabdus budapestensis SN84. The structures of
      the peptides were elucidated on the basis of extensive mass spectrometry (MS),
      and nuclear magnetic resonance analyses. 3, 4, and 7 were novel compounds. 1, 2,
      5, and 6 were isolated and purified for the first time, despite being previously
      elucidated from an extract mixture based on labeling and MS experiments. All
      seven compounds were tested for their nematicidal activities against the second
      stage juveniles (J2) of Meloidogyne incognita using 24-microwell plates.
      Rhabdopeptide J, 2, demonstrated strong inhibitory activity with an LC50 value of
      27.8 MUg/mL. Rhabdopeptide K, 3, and M, 5, showed moderate inhibitory activity
      with LC50 values of 46.3 and 42.4 MUg/mL, respectively.

PMID- 29597343
TI  - Dopamine D1-Like Receptor Agonist and D2-Like Receptor Antagonist (-)
      Stepholidine Reduces Reinstatement of Drug-Seeking Behavior for 3,4
      Methylenedioxypyrovalerone (MDPV) in Rats.
AB  - Psychostimulant reinforcement is mediated by stimulation of both dopamine (DA) D1
      like and D2-like receptors, suggesting that pharmacotherapy agents with a dual DA
      receptor mechanism may be useful for managing psychostimulant abuse. (-)
      Stepholidine (L-SPD) is a Chinese herbal extract that functions as a D1-like
      receptor agonist and D2-like receptor antagonist. L-SPD has been shown to
      attenuate the reinforcing effects of heroin; however, its effects on the
      synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined.
      The current study determined the effects of L-SPD on reinstatement of MDPV
      seeking behavior in the drug intravenous self-administration (IVSA) and
      conditioned place preference (CPP) paradigms. To determine whether the effects of
      L-SPD were specific to psychostimulant reinforcement, we also examined its
      effects on sucrose-seeking behavior. Using a locomotor activity assay, we tested
      the locomotor effects of L-SPD, as well as its effects on MDPV-induced
      hyperactivity. The results of a battery of in vitro binding and functional assays
      confirmed that L-SPD functioned as a D1-like receptor agonist and D2-like
      receptor antagonist. In behavioral experiments, L-SPD dose-dependently attenuated
      cue plus MDPV-primed reinstatement of MDPV-seeking behavior in the IVSA model.
      The highest dose of L-SPD also attenuated MDPV-primed reinstatement of MDPV CPP,
      as well as cue-induced reinstatement of sucrose-seeking. L-SPD had no significant
      locomotor effects, and did not modulate the robust hyperactivity induced by MDPV.
      The current findings show for the first time a robust reinstatement effect with
      MDPV, which can be reduced by L-SPD. These results establish a role for DA
      receptors in drug-seeking behavior for MDPV.

PMID- 29597346
TI  - Porosity Prediction through Hydrogen Bonding in Covalent Organic Frameworks.
AB  - Easy and bulk-scale syntheses of two-dimensional (2D) covalent organic frameworks
      (COFs) represent an enduring challenge in material science. Concomitantly, the
      most critical aspect is to precisely control the porosity and crystallinity of
      these robust structures. Disparate complementary approaches such as solvothermal
      synthesis have emerged recently and are fueled in part by the usage of different
      modulators and acids that have enriched the COF library. Yet, the fundamental
      understanding of the integral processes of 2D COF assembly, including their
      growth from nucleating sites and the origin of periodicity, is an intriguing
      chemical question that needs to be answered. To address these cardinal questions,
      a green and easy-to-perform approach of COF formation has been delineated
      involving acid-diamine salt precursors. The role of hydrogen bonding [ dav(Namine
      H...Oacid); dav signifies the average Namine-H...Oacid distances, i.e., the
      average distance from the H atom of the amine to the O atom of the acid] present
      in the acid-diamine salts in improving the COFs' crystallinity and porosity has
      further been decoded by thorough crystallographic analyses of the salt molecules.
      What is particularly noteworthy is that we have established the hydrogen-bonding
      distances dav(Namine-H...Oacid) in the acid-diamine salts that are pivotal in
      maintaining the reversibility of the reaction, which mainly facilitates highly
      crystalline and porous COF formation. Moreover, this reactant-structure to the
      product-quality relationship has further been utilized for the synthesis of
      highly crystalline and porous COFs that are unattainable by other synthetic
      means.

PMID- 29597345
TI  - DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in
      Early Life.
AB  - Maternal exposure to airborne particulate matter (PM) has been associated with
      restricted fetal growth and reduced birthweight. Here, we performed methylome
      wide analyses of cord and children's blood DNA in relation to residential
      exposure to PM smaller than 10 MUm (PM10). This study included participants of
      the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n =
      780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth
      cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n =
      84), Piccolipiu ( n = 99) and Rhea ( n = 75). We could not identify significant
      CpG sites, by meta-analyzing associations between maternal PM10 exposure during
      pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and
      concordant annual exposure at 7 and 15-17 years. The CpG cg21785536 was inversely
      associated with PM10 exposure using a longitudinal model integrating the three
      studied age groups (-1.2% per 10 MUg/m3; raw p-value = 3.82 * 10-8). Pathway
      analyses on the corresponding genes of the 100 strongest associated CpG sites of
      the longitudinal model revealed enriched pathways relating to the GABAergic
      synapse, p53 signaling and NOTCH1. We provided evidence that residential PM10
      exposure in early life affects methylation of the CpG cg21785536 located on the
      EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.

PMID- 29597347
TI  - Enzymatic Preparation of a Homologous Series of Long-Chain 6- O-Acylglucose
      Esters and Their Evaluation as Emulsifiers.
AB  - Sugar fatty acid esters are nonionic surfactants that are widely exploited in the
      food and cosmetics industries, as well as in the oral care and medical supply
      fields. Accordingly, new methods for their selective synthesis and the "tuning"
      of their emulsifying properties are of considerable interest. Herein we report
      simple and irreversible enzymatic esterifications of d-glucose with seven fatty
      acid vinyl esters. The foaming and emulsifying effects of the resulting 6- O
      acylglucose esters were then evaluated. In accord with expectations, when the
      length of the alkyl side chain associated with the 6- O-acylglucose esters
      increases, then their hydrophilic-lipophilic balance (HLB) values decrease, while
      the stabilities of the derived emulsions improve. In order to maintain good
      foaming properties, alkyl side chains of at least 9 to 11 carbons in length are
      required. In the first such assays on 6- O-acylglucose esters, most of those
      described herein are shown to be nontoxic to the HepG2, MCF-7, LNacp, SW549, and
      LO-2 cell lines.

PMID- 29597348
TI  - Infrared Photodissociation Spectra of [Sn(CO2) n]- Cluster Ions.
AB  - We present infrared spectra and density functional theory calculations of mass
      selected [Sn(CO2) n]- cluster anions ( n = 2-6). The spectra and structures of
      these clusters exhibit less structural diversity than those of analogous clusters
      with first-row transition metals, but are more complex than those for the heavy
      coinage metals or for the related [Bi(CO2) n]- clusters. The most favorable core
      ion structure for all cluster sizes can be characterized as a Sn-oxalate complex,
      Sn[C2O4]-. Higher energy isomers based on a bidentate eta2-(C,O) CO2 ligand
      tightly bound to the metal atom in SnCO2- complexes are also observed, even for
      the largest cluster sizes studied here. For n = 2, another high energy isomer is
      found, featuring a CO2 ligand weakly bound to the metal atom in a SnCO2- ion.

PMID- 29597349
TI  - Numerical Study of Surfactant Dynamics during Emulsification in a T-Junction
      Microchannel.
AB  - Microchannel emulsification requires large amounts of surfactant to prevent
      coalescence and improve emulsions lifetime. However, most numerical studies have
      considered surfactant-free mixtures as models for droplet formation in
      microchannels, without taking into account the distribution of surfactant on the
      droplet surface. In this paper, we investigate the effects of nonuniform
      surfactant coverage on the microfluidic flow pattern using an extended lattice
      Boltzmann model. This numerical study, supported by micro-particle image
      velocimetry experiments, reveals the likelihood of uneven distribution of
      surfactant during the droplet formation and the appearance of a stagnant cap. The
      Marangoni effect affects the droplet breakup by increasing the shear rate.
      According to our results, surfactant-free and surfactant-rich droplet formation
      processes are qualitatively different, such that both the capillary number and
      the Damkohler number should be considered when modeling the droplet generation in
      microfluidic devices. The limitations of traditional volume and pressure
      estimation methods for determining the dynamic interfacial tension are also
      discussed on the basis of the simulation results.

PMID- 29597350
TI  - Atomic Force Microscopy and Angular-Dependent X-ray Photoelectron Spectroscopy
      Studies of Anchored Quaternary Ammonium Salt Biocides on Quartz Surfaces.
AB  - A siloxane surface-anchored quaternary ammonium salt (AQAS: BIOSAFE HM4100 in
      this study) has been chemisorbed onto a quartz substrate. The aim of this study
      is to elucidate, using atomic force microscopy (AFM) and X-ray photoelectron
      spectroscopy (XPS), the structure of the chemisorbed AQAS layers. The AQAS
      biocide includes a C18 alkyl chain previously invoked in lysis potency. The AQAS
      coverage appears in zones on the surface, which include a first layer (2.6 +/-
      0.1 nm) and multilayering that were explored using AFM. The XPS data exhibited
      two N 1s signals at about 402 and 399 eV, with only the former exhibiting angular
      dependence. This signal at 402 eV was assigned to the first anchored layer with
      perpendicular orientation determined by the AQAS anchoring to the surface. In
      preliminary AFM studies of bacteria on these AQAS surfaces, perturbations on the
      Staphylococcus aureus cells and the degradation of Escherichia coli cells suggest
      lysis potency.

PMID- 29597351
TI  - Fluorescent Supracolloidal Chains of Patchy Micelles of Diblock Copolymers
      Functionalized with Fluorophores.
AB  - By selective attachment of fluorescent dyes to the core-forming block, we
      produced patchy micelles of diblock copolymers with fluorophores localized in the
      micellar cores. From these patchy micelles functionalized with dyes, fluorescent
      supracolloidal chains in a few micrometers were polymerized by combining the
      patches in neighboring micelles, indicating that selective modification of the
      core-forming block delivered the functionality into the supracolloidal chain
      without altering the polymerization of patchy micelles. Thus, with the same
      polymerization condition, we were able to produce red-, green-, and blue-emitting
      supracolloidal chains by varying the fluorescent dyes attached to the core
      forming block. In addition, we directly visualized individual supracolloidal
      chains by fluorescence confocal microscopy as well as by transmission electron
      microscopy.

PMID- 29597352
TI  - Clostridium difficile toxins A and B decrease intestinal SLC26A3 protein
      expression.
AB  - Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhea
      in the United States. Although C. difficile toxins A and B are the primary
      mediators of CDI, the overall pathophysiology underlying C. difficile-associated
      diarrhea remains poorly understood. Studies have shown that a decrease in both
      NHE3 (Na+/H+ exchanger) and DRA (downregulated in adenoma, Cl-/[Formula: see
      text] exchanger), resulting in decreased electrolyte absorption, is implicated in
      infectious and inflammatory diarrhea. Furthermore, studies have shown that NHE3
      is depleted at the apical surface of intestinal epithelial cells and
      downregulated in patients with CDI, but the role of DRA in CDI remains unknown.
      In the current studies, we examined the effects of C. difficile toxins TcdA and
      TcdB on DRA protein and mRNA levels in intestinal epithelial cells (IECs). Our
      data demonstrated that DRA protein levels were significantly reduced in response
      to TcdA and TcdB in IECs in culture. This effect was also specific to DRA, as
      NHE3 and PAT-1 (putative anion transporter 1) protein levels were unaffected by
      TcdA and TcdB. Additionally, purified TcdA and TcdA + TcdB, but not TcdB,
      resulted in a decrease in colonic DRA protein levels in a toxigenic mouse model
      of CDI. Finally, patients with recurrent CDI also exhibited significantly reduced
      expression of colonic DRA protein. Together, these findings indicate that C.
      difficile toxins markedly downregulate intestinal expression of DRA which may
      contribute to the diarrheal phenotype of CDI. NEW & NOTEWORTHY Our studies
      demonstrate, for the first time, that C. difficile toxins reduce DRA protein, but
      not mRNA, levels in intestinal epithelial cells. These findings suggest that a
      downregulation of DRA may be a critical factor in C. difficile infection
      associated diarrhea.

PMID- 29597353
TI  - Extracellular adenosine: a critical signal in liver fibrosis.
AB  - Extracellular adenosine nucleoside is a potent, endogenous mediator that signals
      through specific G protein-coupled receptors, and exerts pleiotropic effects on
      liver physiology, in health and disease. Particularly, adenosinergic or adenosine
      mediated signaling pathways impact the progression of hepatic fibrosis, a common
      feature of chronic liver diseases, through regulation of matrix deposition by
      liver myofibroblasts. This review examines the current lines of evidence on
      adenosinergic regulation of liver fibrosis and myofibroblasts, identifies
      unanswered research questions, and proposes important future areas of
      investigation.

PMID- 29597354
TI  - Protein fermentation in the gut; implications for intestinal dysfunction in
      humans, pigs, and poultry.
AB  - The amount of dietary protein is associated with intestinal disease in different
      vertebrate species. In humans, this is exemplified by the association between
      high-protein intake and fermentation metabolite concentrations in patients with
      inflammatory bowel disease. In production animals, dietary protein intake is
      associated with postweaning diarrhea in piglets and with the occurrence of wet
      litter in poultry. The underlying mechanisms by which dietary protein contributes
      to intestinal problems remain largely unknown. Fermentation of undigested protein
      in the hindgut results in formation of fermentation products including short
      chain fatty acids, branched-chain fatty acids, ammonia, phenolic and indolic
      compounds, biogenic amines, hydrogen sulfide, and nitric oxide. Here, we review
      the mechanisms by which these metabolites may cause intestinal disease. Studies
      addressing how different metabolites induce epithelial damage rely mainly on cell
      culture studies and occasionally on mice or rat models. Often, contrasting
      results were reported. The direct relevance of such studies for human, pig, and
      poultry gut health is therefore questionable and does not suffice for the
      development of interventions to improve gut health. We discuss a roadmap to
      improve our understanding of gut metabolites and microbial species associated
      with intestinal health in humans and production animals and to determine whether
      these metabolite/bacterial networks cause epithelial damage. The outcomes of
      these studies will dictate proof-of-principle studies to eliminate specific
      metabolites and or bacterial strains and will provide the basis for interventions
      aiming to improve gut health.

PMID- 29597355
TI  - Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch.
AB  - The last few decades have seen a major increase in the number of
      neurotransmitters and neuropeptides recognized as playing a role in brain stem
      neurocircuits, including those involved in homeostatic functions such as stress
      responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness.
      This minireview will focus on the known physiological role of three of these
      novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special
      emphasis on their hypothetical roles in vagal signaling related to
      gastrointestinal motor functions.

PMID- 29597831
TI  - Developmental differences in focal adhesion kinase expression modulate pulmonary
      endothelial barrier function in response to inflammation.
AB  - Compromised pulmonary endothelial cell (PEC) barrier function characterizes acute
      respiratory distress syndrome (ARDS), a cause of substantial morbidity and
      mortality. Survival from ARDS is greater in children compared with adults.
      Whether developmental differences intrinsic to PEC barrier function contribute to
      this survival advantage remains unknown. To test the hypothesis that PEC barrier
      function is more well-preserved in neonatal lungs compared with adult lungs in
      response to inflammation, we induced lung injury in neonatal and adult mice with
      systemic lipopolysaccharide (LPS). We assessed PEC barrier function in vivo and
      in vitro, evaluated changes in the expression of focal adhesion kinase 1 (FAK1)
      and phosphorylation in response to LPS, and determined the effect of FAK
      silencing and overexpression on PEC barrier function. We found that LPS induced a
      greater increase in lung permeability and PEC barrier disruption in the adult
      mice, despite similar degrees of inflammation and apoptosis. Although baseline
      expression was similar, LPS increased FAK1 expression in neonatal PEC but
      increased FAK1 phosphorylation and decreased FAK1 expression in adult PEC.
      Pharmacologic inhibition of FAK1 accentuated LPS-induced barrier disruption most
      in adult PEC. Finally, in response to LPS, FAK silencing markedly impaired
      neonatal PEC barrier function, whereas FAK overexpression preserved adult PEC
      barrier function. Thus, developmental differences in FAK expression during
      inflammatory injury serve to preserve neonatal pulmonary endothelial barrier
      function compared with that of adults and suggest that intrinsic differences in
      the immature versus pulmonary endothelium, especially relative to FAK1
      phosphorylation, may contribute to the improved outcomes of children with ARDS.

PMID- 29597356
TI  - Complement Factor D protects mice from ethanol-induced inflammation and liver
      injury.
AB  - Complement plays a crucial role in microbial defense and clearance of apoptotic
      cells. Emerging evidence suggests complement is an important contributor to
      alcoholic liver disease. While complement component 1, Q subcomponent (C1q)
      dependent complement activation contributes to ethanol-induced liver injury, the
      role of the alternative pathway in ethanol-induced injury is unknown. Activation
      of complement via the classical and alternative pathways was detected in
      alcoholic hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient (
      C1qa-/-, lacking classical pathway activation), complement protein 4-deficient (
      C4-/-, lacking classical and lectin pathway activation), complement factor D
      deficient ( FD-/-, lacking alternative pathway activation), and C1qa/FD-/-
      (lacking classical and alternative pathway activation) mice were fed an ethanol
      containing liquid diet or pair-fed control diet for 4 or 25 days. Following
      chronic ethanol exposure, liver injury, steatosis, and proinflammatory cytokine
      expression were increased in WT but not C1qa-/-, C4-/-, or C1qa/FD-/- mice. In
      contrast, liver injury, steatosis, and proinflammatory mediators were robustly
      increased in ethanol-fed FD-/- mice compared with WT mice. Complement activation,
      assessed by hepatic accumulation of C1q and complement protein 3 (C3) cleavage
      products (C3b/iC3b/C3c), was evident in livers of WT mice in response to both
      short-term and chronic ethanol. While C1q accumulated in ethanol-fed FD-/- mice
      (short term and chronic), C3 cleavage products were detected after short-term but
      not chronic ethanol. Consistent with impaired complement activation, chronic
      ethanol induced the accumulation of apoptotic cells and fibrogenic responses in
      the liver of FD-/- mice. These data highlight the protective role of complement
      factor D (FD) and suggest that FD-dependent amplification of complement is an
      adaptive response that promotes hepatic healing and recovery in response to
      chronic ethanol. NEW & NOTEWORTHY Complement, a component of the innate immune
      system, is an important pathophysiological contributor to ethanol-induced liver
      injury. We have identified a novel role for factor D, a component of the
      alternative pathway, in protecting the liver from ethanol-induced inflammation,
      accumulation of apoptotic hepatocytes, and profibrotic responses. These data
      indicate a dual role of complement with regard to inflammatory and protective
      responses and suggest that accumulation of apoptotic cells impairs hepatic
      healing/recovery during alcoholic liver disease.

PMID- 29597832
TI  - Maternal omega-3 PUFA supplementation prevents hyperoxia-induced pulmonary
      hypertension in the offspring.
AB  - Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 16-25%
      of premature infants with bronchopulmonary dysplasia (BPD), contributing
      significantly to perinatal morbidity and mortality. Omega-3 polyunsaturated fatty
      acids (PUFA omega-3) can improve vascular remodeling, angiogenesis, and
      inflammation under pathophysiological conditions. However, the effects of PUFA
      omega-3 supplementation in BPD-associated PH are unknown. The present study aimed
      to evaluate the effects of PUFA omega-3 on pulmonary vascular remodeling,
      angiogenesis, and inflammatory response in a hyperoxia-induced rat model of PH.
      From embryonic day 15, pregnant Sprague-Dawley rats were supplemented daily with
      PUFA omega-3, PUFA omega-6, or normal saline (0.2 ml/day). After birth, pups were
      pooled, assigned as 12 per litter, randomly assigned to either air or continuous
      oxygen exposure (fraction of inspired oxygen = 85%) for 20 days, and then
      euthanized for pulmonary hemodynamic and morphometric analysis. We found that
      PUFA omega-3 supplementation improved survival, decreased right ventricular
      systolic pressure and RVH caused by hyperoxia, and significantly improved
      alveolarization, vascular remodeling, and vascular density. PUFA omega-3
      supplementation produced a higher level of total omega-3 in lung tissue and
      breast milk and was found to reverse the reduced levels of VEGFA, VEGF receptor
      2, angiopoietin-1 (ANGPT1), endothelial TEK tyrosine kinase, endothelial nitric
      oxide synthase, and nitric oxide concentrations in lung tissue and the increased
      ANGPT2 levels in hyperoxia-exposed rats. The beneficial effects of PUFA omega-3
      in improving lung injuries were also associated with an inhibition of leukocyte
      infiltration and reduced expression of the proinflammatory cytokines IL-1beta, IL
      6, and TNF-alpha. These data indicate that maternal PUFA omega-3 supplementation
      strategies could effectively protect against infant PH induced by hyperoxia.

PMID- 29597833
TI  - Editorial Comment on: Externalized Ureteral Catheter Versus Double-J Stent in
      Tubeless Percutaneous Nephrolithotomy for Upper Urinary Stones: A Systematic
      Review and Meta-Analysis by Chen et al.

PMID- 29597834
TI  - New dianthramide and cinnamic ester glucosides from the roots of Aconitum
      carmichaelii.
AB  - Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'
      dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-beta-D
      allopyranosyl-ferulate (3), and methyl-4-beta-D-gulopyranosyl-cinnamate (4),
      along with six known compounds (5-10), were isolated from the roots of Aconitum
      carmichelii Debx. Their structures were elucidated on the basis of spectral data
      analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the
      inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94
      MUM, respectively.

PMID- 29597835
TI  - Editorial Comment on: The Impact of Thiazides and Potassium Citrate on Bone
      Mineral Density Evaluated by CT Scan in Stone Formers by Alshara et al.

PMID- 29597836
TI  - Validation of a Novel Cost Effective Easy to Produce and Durable In Vitro Model
      for Kidney-Puncture and Percutaneous Nephrolitholapaxy-Simulation.
AB  - INTRODUCTION: Nephrolithiasis is one of the most common diseases in urology.
      According to the EAU Guidelines, a percutaneous nephrolitholapaxy (PNL) is
      recommended when treating a kidney stone >2 cm. Nowadays, PNL is performed even
      for smaller stones (<1 cm) using miniaturized instruments. The most challenging
      part of any PNL is the puncture of the planned site. PNL-novice surgeons need to
      practice this step in a safe environment with an ideal training model. We
      developed and evaluated a new, easy to produce, in vitro model for the training
      of the freehand puncture of the kidney. MATERIALS AND METHODS: Porcine kidneys
      with ureters were embedded in ballistic gel. Food coloring and preservative agent
      were added. We used the standard imaging modalities of X-ray and ultrasound to
      validate the training model. An additional new technique, the iPAD-guided
      puncture, was evaluated. Five novices and three experts conducted 12 punctures
      for each imaging technique. Puncture time, radiation dose, and number of attempts
      to a successful puncture were measured. Mann-Whitney-U, Kruskal-Wallis, and U
      Tests were used for statistical analyses. RESULTS: The sonography-guided puncture
      is slightly but not significantly faster than the fluoroscopy-guided puncture and
      the iPAD-assisted puncture. Similarly, the most experienced surgeon's time for a
      successful puncture was slightly less than that of the residents, and the
      experienced surgeons needed the least attempts to perform a successful puncture.
      In terms of radiation exposure, the residents had a significant reduction of
      radiation exposure compared to the experienced surgeons. CONCLUSION: The newly
      developed ballistic gel kidney-puncture model is a good training tool for a
      variety of kidney-puncture techniques, with good content, construct, and face
      validity.

PMID- 29597872
TI  - A Description and Evaluation of the Concussion Education Application HEADS UP
      Rocket Blades.
AB  - BACKGROUND: Concussions are responsible for numerous emergency department visits
      and hospitalizations among children annually. However, there remains a great deal
      of confusion about how to prevent and manage concussions in youth. To teach
      children aged 6 to 8 years about concussion safety, the Centers for Disease
      Control and Prevention (CDC) created a mobile gaming application called HEADS UP
      Rocket Blades. This report introduces the game and presents findings on its
      evaluation. METHODS: The aim of the game is to teach children what a concussion
      is, its commons signs and symptoms, how to prevent one, and what to do if one
      occurs. An early version of the game went through two rounds of usability testing
      with children and parents to obtain initial impressions and make improvements.
      RESULTS: The first round of usability testing focused on the mechanics of the
      game. Based on feedback from this session, CDC and the developers simplified the
      messaging and adjusted the game's level of difficulty. The second round focused
      on the gaming experience. The children indicated that they enjoyed playing, and
      nearly all were able to relay at least one learning objective. CONCLUSIONS:
      Parents and children rated Rocket Blades as a good learning tool and indicated
      that they would download it for personal use.

PMID- 29597873
TI  - HPV Knowledge and Vaccine Initiation Among Mexican-Born Farmworkers in North
      Carolina.
AB  - The human papilloma virus (HPV) vaccine is an effective but underused cancer
      prevention tool. This study assessed knowledge of HPV and HPV vaccine initiation
      among Mexican-born farmworkers in North Carolina. Interviewer-administered
      questionnaires were conducted with 100 Latino farmworkers and 100 nonfarmworker
      Latino North Carolina residents in 2015 as part of an ongoing community-based
      participatory research project. Farmworkers had low levels of knowledge about HPV
      and the HPV vaccine. They had a similar amount of HPV and HPV vaccine knowledge
      compared to nonfarmworkers. Farmworkers and nonfarmworkers learned about the HPV
      vaccine from different sources. Adolescent children of farmworkers and
      nonfarmworkers had low HPV vaccine initiation. However, for children living in
      the United States with farmworker parents, vaccine initiation was high. To
      prevent HPV-related cancers and improve health equity, interventions are needed
      in order to increase HPV education and vaccine initiation among children of
      Mexican-born farmworkers and nonfarmworkers. Public health programs should look
      for partners outside the traditional health care setting to reach underserved
      populations. Other key strategies include promoting catch-up vaccines, improving
      patient-provider communication, and providing case management services.

PMID- 29597874
TI  - The Role and Influence of Prostate Cancer Caregivers Across the Care Continuum.
AB  - BACKGROUND: Black men endure a disproportionate burden of morbidity and mortality
      related to prostate cancer (CaP). Increasingly family members are assuming the
      role of providing care and support to family members with chronic disease.
      Understanding the role and influence of the caregiver is a necessary part of
      developing resources to assist individuals learning to provide care. AIM: The
      analysis aimed to explore CaP survivors' perceptions of the role and influence of
      family caregivers to better understand existing opportunities for improving
      experiences and outcomes for both the caregiver and the care receiver. DESIGN:
      Secondary analysis of qualitative interview transcripts. Data were analyzed to
      explore new inquiries related to CaP survivors' perceptions of family caregivers'
      role and influence at each stage of care. Content analysis was used to group data
      into established categories. DATA SOURCE: Data included qualitative interview
      transcripts with 32 CaP survivors from the Florida Prostate Cancer Care and
      Survivorship Project. RESULTS: The role of the family caregiver is complex.
      Caregivers in this community seem to have a significant influence on behavior
      modification and cues to action for Black men with prostate cancer. According to
      the men in this group, caregivers functioned as normalizing agents, coordinating
      care and creating a new normal, throughout the various stages of care and
      survivorship. CONCLUSIONS: Findings inform areas for future research to develop
      culturally tailored health promotion programs designed to improve outcomes and
      address the needs of both the family caregiver and the care receiver across the
      care continuum.

PMID- 29597875
TI  - Aneurin Bevan's long shadow over 70 years of the British National Health Service.
AB  - The years approaching the 70th anniversary of the British National Health Service
      (NHS) have seen some re-assessment of the role of the Labour party in general,
      and Minister of Health, Aneurin Bevan in particular, in the creation of the NHS.
      It is clear that Bevan casts a long shadow over the NHS. In terms of 'history as
      invocation', Bevan can be invoked in different ways. Put another way, different
      Bevans cast a variety of shadows. This article explores: Bevan as the embodiment
      of the NHS; Bevan as rhetoric; Bevan as trust; and Bevan as reassurance. It
      concludes that Bevan has rightly cast his long shadow over the 70 years of the
      NHS. However, it is important to recognise the different Bevan reference points
      for their different reasons. However, there is one surprising omission. As a
      present to the NHS on its 70th birthday, perhaps it is time to rename this type
      as a 'Bevan' system?

PMID- 29597876
TI  - AMPKalpha2 deficiency enhanced susceptibility to ventricular arrhythmias in mice
      by the role of beta-adrenoceptor signaling.
AB  - AMP-activated protein kinase-alpha2 is the main catalytic subunit of the heart,
      which is mainly located in cardiac myocytes. The effect of AMP-activated protein
      kinase-alpha2 on the cardiac electrophysiology is barely studied. From the
      previous study, it is possible that AMP-activated protein kinase-alpha2 may have
      some effect on the electrophysiology of the heart. To prove the hypothesis, we
      used the AMP-activated protein kinase-alpha2 knockout (AMPKalpha2-/-) mice to
      estimate the electrophysiological characteristics of AMPKalpha2-/- mice and try
      to find the mechanism between them. We used AMP-activated protein kinase-alpha2
      gene knockout (AMPKalpha2-/-) mice and control wild-type mice as the experimental
      animals. In the experiment, we measured the monophasic action potential duration
      and test the inducibility to ventricular arrhythmia in isolated mice heart with
      and without beta-adrenoceptor antagonist metoprolol. Meanwhile, plasma
      concentration of catecholamine was collected. We found that AMPKalpha2-/-
      significantly shortened 90% repolarization of monophasic action potential (MAP)
      (MAPD90) than wild-type (47.4 +/- 2.6 ms vs. 55.5 +/- 2.4 ms, n = 10, P < 0.05)
      and were more vulnerable to be induced to ventricular arrhythmias (70% (7/10) vs.
      10% (1/10), P < 0.05), accompanied by the higher concentration of catecholamine
      (epinephrine: 1.75 +/- 0.18 nmol/L vs. 0.68 +/- 0.10 nmol/L n = 10, P < 0.05;
      norepinephrine: 9.56 +/- 0.71 nmol/L vs. 2.52 +/- 0.31 nmol/L n = 10, P < 0.05).
      The shortening of MAPD90 and increased inducibility to ventricular arrhythmias of
      AMPKalpha2-/- could almost be abolished when perfusion with beta-adrenoceptor
      antagonist metoprolol. It indicated that the beta-adrenoceptor activation
      resulting from catecholamine release was mainly responsible for the relating
      changes of electrophysiology of AMPKalpha2-/-. It had great clinical
      significance, as in patients who had problem with AMP-activated protein kinase
      alpha2 gene, we might use beta-adrenoceptor antagonists as the prevention of
      arrhythmias in future. Impact statement As far as we know, this is the first time
      the role of AMP-activated protein kinase-alpha2 (AMPKalpha2) on the cardiac
      electrophysiology is explored, and we found that the beta-adrenoceptor activation
      resulting from catecholamine release was mainly responsible for the changes of
      electrophysiology related to the absence of AMPKalpha2. This has great clinical
      significance, as in patients who have problems with AMPKalpha2 gene, we may use
      beta-adrenoceptor antagonists for the prevention of arrhythmias in future.

PMID- 29597877
TI  - EB 2017 Article: Interpretation of the lactulose:mannitol test in rural Malawian
      children at risk for perturbations in intestinal permeability.
AB  - The dual sugar absorption test, specifically the lactulose:mannitol test, is used
      to assess gut health. Lactulose absorption is said to represent gut damage and
      mannitol absorption is used as a measure of normal small bowel function and
      serves as normalizing factor for lactulose. A underappreciated limitation of this
      common understanding of the lactulose:mannitol test is that mannitol is not
      absorbed to any substantial extent by a transcellular process. Additionally, this
      interpretation of lactulose:mannitol is not consistent with current understanding
      of paracellular pathways, where three pathway types exist: pore, leak, and
      unrestricted. Pore and leak pathways are regulated biological constructions of
      the small bowel barrier, and unrestricted pathways represent micropathological
      damage. We analyzed 2334 lactulose:mannitol measurements rigorously collected
      from 622 young rural Malawian children at high risk for poor gut health in light
      of the pathway model. An alternative method of normalizing for gut length
      utilizing autopsy data is described. In our population, absorbed lactulose and
      mannitol are strongly correlated, r = 0.68 P <0.0001, suggesting lactulose and
      mannitol are traversing the gut barrier via the same pathways. Considering
      measurements where pore pathways predominate, mannitol flux is about 14 times
      that of lactulose. As more leak pathways are present, this differential flux
      mannitol:lactulose falls to 8:1 and when increased numbers of unrestricted
      pathways are present, the differential flux of mannitol:lactulose is 6:1. There
      was no substantial correlation between the lactulose:mannitol and linear growth.
      Given that mannitol will always pass through a given pathway at a rate at least
      equal to that of lactulose, and lactulose absorption is a composite measure of
      flux through both physiologic and pathologic pathways, we question the utility of
      the lactulose:mannitol test. We suggest using lactulose alone is as informative
      as lactulose:mannitol in a sugar absorption testing in subclinical gut
      inflammation. Impact statement Our work integrates the standard interpretation of
      the lactulose:mannitol test (L:M), with mechanistic insight of intestinal
      permeability. There are three paracellular pathways in the gut epithelium; pore,
      leak, and unrestricted. Using thousands of L:M measurements from rural Malawian
      children at risk for increased intestinal permeability, we predict the
      differential flux of L and M through the pathways. Our findings challenge the
      traditional notions that little L is absorbed through a normal epithelial barrier
      and that M is a normalizing factor for L. Our observations are consistent with
      pore pathways allowing only M to pass. And that substantial amounts of L and M
      pass through leak pathways which are normal, regulated, cell-junctional
      adaptations. So M is a composite measure of all pathways, and L is not a measure
      solely of pathologic gut damage. Using L alone as a probe will yield more
      information about gut health than L:M.

PMID- 29597895
TI  - In Vivo Genome Editing Partially Restores Alpha1-Antitrypsin in a Murine Model of
      AAT Deficiency.
AB  - CRISPR (clustered regularly interspaced short palindromic repeats) genome editing
      holds promise in the treatment of genetic diseases that currently lack effective
      long-term therapies. Patients with alpha-1 antitrypsin (AAT) deficiency develop
      progressive lung disease due to the loss of AAT's antiprotease function and liver
      disease due to a toxic gain of function of the common mutant allele. However, it
      remains unknown whether CRISPR-mediated AAT correction in the liver, where AAT is
      primarily expressed, can correct either or both defects. Here we show that AAV
      delivery of CRISPR can effectively correct Z-AAT mutation in the liver of a
      transgenic mouse model. Specifically, we co-injected two AAVs: one expressing
      Cas9 and another encoding an AAT guide RNA and homology-directed repair template.
      In both neonatal and adult mice, this treatment partially restored M-AAT in the
      serum. Furthermore, deep sequencing confirmed both indel mutations and precise
      gene correction in the liver, permitting careful analysis of gene editing events
      in vivo. This study demonstrates a proof of concept for the application of CRISPR
      Cas9 technology to correct AAT mutations in vivo and validates continued
      exploration of this approach for the treatment of patients with AAT deficiency.

PMID- 29597932
TI  - Synthesis and antitumor, antityrosinase, and antioxidant activities of xanthone.
AB  - Ten substituted 1,3-dihydroxyxanthones were synthesized in one step. The yields
      ranged from 40 to 76%. Compounds 8-10 were first reported. Next, the compounds'
      in vitro anti-proliferative activities against nine human cancer cell lines,
      antityrosinase, and antioxidant activities were evaluated. Compounds 1, 4, 6-7,
      and 9-10 exhibited enhanced cytotoxicity against certain cancer cells. Compounds
      2, 8, 9, and 10 inhibited tyrosinase activity to a certain extent. In addition,
      compound 4 exhibited the best antioxidant activity, which was consistent with
      theoretical calculations. These results demonstrated that compounds 1-2, 4, and 6
      10 were promising leads for further investigation.

PMID- 29597981
TI  - Editorial Comment on: "STONE TREES": Metabolic Evaluation and Medical Treatment
      of the Urolithiasis Patient Made Easy by Clayman et al.

PMID- 29597982
TI  - Fluoride removal from groundwater using chemically modified rice husk and corn
      cob activated carbon.
AB  - The fluoride adsorption potential of chemically modified rice husk and corn cob
      activated carbon was investigated in batch and column tests. The effect of pH,
      contact time, initial fluoride concentration and adsorbent dose on the adsorption
      capacity and efficiency was studied. Batch experimental results were analysed
      using analysis of variance. The maximum adsorption capacity of 7.9 and 5.8 mg/g
      and a removal efficiency of 91% and 89% were achieved in batch tests,
      respectively, for rice husk and corn cob activated carbon. The adsorption data
      and kinetic model fitted well to the Langmuir isotherm and pseudo-second-order
      kinetics, respectively. Fluoride adsorption was governed by both intraparticle
      diffusion and surface or film diffusion for both rice husk and corn cob activated
      carbon. Continuous tests were carried out using three columns packed with 100%
      rice husk activated carbon, 100% corn cob activated carbon and 50% rice husk +
      50% corn cob activated carbon. The breakthrough adsorption capacities were found
      to be 7.9, 5.0 and 5.2 mg/g, respectively. The results were analysed using the
      Thomas model, which yielded adsorption capacities of 11, 8.1 and 9.4 mg/g,
      respectively, for the three columns investigated.

PMID- 29598006
TI  - Editorial Comment on: Automated Computer Software Compared with Manual
      Measurements for CT-Based Urinary Stone Metrics: An Evaluation Study by Bell et
      al.

PMID- 29598007
TI  - AAV6-Mediated IL-10 Expression in the Lung Ameliorates Bleomycin-Induced
      Pulmonary Fibrosis in Mice.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder with limited
      therapeutic options. An aberrant wound healing process in response to repetitive
      lung injury has been suggested for its pathogenesis, and a number of cytokines
      including transforming growth factor beta1 play pivotal roles in the induction
      and progression of fibrosis. Thus, the regulation of these pro-inflammatory
      conditions may reduce the progression of IPF and ameliorate its symptoms in
      patients. Interleukin-10 (IL-10), a pleiotropic cytokine, exerts anti
      inflammatory and anti-fibrotic effects in numerous biological settings. In the
      present study, we investigated the preventive effects of IL-10 on bleomycin
      induced pulmonary fibrosis in mice with the continuous expression of this
      cytokine via an adeno-associated virus serotype 6 vector. Mice were administered
      the adeno-associated virus serotype 6 vector encoding mouse IL-10 by
      intratracheal injection, and osmotic minipumps containing bleomycin were
      subcutaneously implanted seven days later. Lung histology and the expression
      levels of pro-inflammatory cytokines and fibrogenic cytokines were then analyzed.
      In mice exhibiting persistent IL-10 expression on day 35, the number of
      infiltrated inflammatory cells and the development of fibrosis in lung tissues
      were significantly reduced. Increases in transforming growth factor beta1 and
      decreases in IFN-gamma were also suppressed in treated animals, with changes in
      these cytokines playing important roles in the pathogenesis of pulmonary
      fibrosis. Furthermore, IL-10 significantly improved survival in bleomycin-induced
      mice. Our results provide insights into the potential benefit of the anti
      fibrotic effects of IL-10 as a novel therapeutic approach for IPF.

PMID- 29598152
TI  - Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients
      with atrial fibrillation in Sweden and the Netherlands.
AB  - OBJECTIVE: There is limited evidence on patients' adherence and the impact of the
      prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed
      to assess secondary adherence to NOACs and to determine the impact of the dosing
      regimen in patients with atrial fibrillation. METHODS: Patients using a NOAC
      between 2009 and 2013 were identified from the nation-wide Swedish Prescribed
      Drug Register and the Dutch regional IADB.nl database. Patients using a
      consistent dosage for at least 180 consecutive days were included. Adherence was
      calculated using the medication possession ratio (MPR) and adjusted for
      overlapping dates. Adherence was defined as a MPR >=0.8. Sensitivity analyses
      were performed using a MPR >=0.9. Logistic regression was performed to compare
      secondary adherence and to explore the influence of the dosing regimen. RESULTS:
      A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was
      96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable
      logistic regression analysis showed that a twice daily regimen had a lower
      likelihood of being secondary adherent compared to a once daily regimen in Sweden
      (odds ratio [OR] 0.21 [95% CI 0.12-0.35]). LIMITATIONS: The influence of
      selection bias introduced by the inclusion criterion of >=2 dispensations
      covering at least 180 days could not be excluded. CONCLUSIONS: This study
      demonstrated that secondary adherence was high in this specific setting among
      patients with at least two initial dispensations of a NOAC covering a minimum of
      180 days. The use of NOACs in a once daily regimen showed higher adherence
      compared to a twice daily regimen.

PMID- 29598153
TI  - Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded
      Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced
      Pluripotent Stem Cells.
AB  - Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by
      progressive motor neuron loss in the spinal cord. It is caused by mutations in
      the survival motor neuron 1 (SMN1) gene. SMN1 has a paralogous gene, survival
      motor neuron 2 (SMN2), in humans that is present in almost all SMA patients. The
      generation and genetic correction of SMA patient-specific induced pluripotent
      stem cells (iPSCs) is a viable, autologous therapeutic strategy for the disease.
      Here, c-Myc-free and non-integrating iPSCs were generated from the urine cells of
      an SMA patient using an episomal iPSC reprogramming vector, and a unique crRNA
      was designed that does not have similar sequences (<=3 mismatches) anywhere in
      the human reference genome. In situ gene conversion of the SMN2 gene to an SMN1
      like gene in SMA-iPSCs was achieved using CRISPR/Cpf1 and single-stranded
      oligodeoxynucleotide with a high efficiency of 4/36. Seamlessly gene-converted
      iPSC lines contained no exogenous sequences and retained a normal karyotype.
      Significantly, the SMN expression and gems localization were rescued in the gene
      converted iPSCs and their derived motor neurons. This is the first report of an
      efficient gene conversion mediated by Cpf1 homology-directed repair in human
      cells and may provide a universal gene therapeutic approach for most SMA
      patients.

PMID- 29598154
TI  - Sorption of antibiotics onto montmorillonite and kaolinite: competition
      modelling.
AB  - Antibiotic contaminants, which are generally present in bi-solute systems, can be
      competitively adsorbed onto clays. Single- and bi-solute sorptions of
      sulfadiazine (SDZ) and ciprofloxacin (CIP) onto montmorillonite and kaolinite
      were investigated at pH values of 5 and 8. Freundlich and Langmuir models were
      used and fit the experimental data well for single-solute sorption. The sorption
      isotherms were nonlinear (NF = 0.265-0.730), and the maximum sorption capacities
      (qmL) of the SDZ and CIP onto montmorillonite were higher than those onto
      kaolinite. The octanol-water distribution ratio (Dow), cation exchange capacity
      (CEC), Brunauer-Emmett-Teller (BET) surface area (ABET), pore size, point of zero
      charge (pHPZC), and basal spacing predominantly affected the Freundlich constant
      (KF) and qmL of SDZ0 and CIP+ at pH 5 more than SDZ- and CIP+/- at pH 8. For bi
      solute sorption, the presence of CIP inhibited the SDZ sorption onto
      montmorillonite and kaolinite. Competitive sorption models such as Sheindorf
      Rebhun-Sheintuch (SRS), Murali-Aylmore (M-A) and the modified extended Langmuir
      model (MELM) were used; of these, the MELM provided the best prediction with SDZ
      sorption onto montmorillonite at pH 8 and CIP onto kaolinite at pH 5 and 8 in
      SDZ/CIP system occurring synergistically, whereas others occurred
      antagonistically. The distribution coefficient (Kd) of the bi-solute sorption
      decreased with increasing pH in the order cationic > neutral > anionic for SDZ
      and cationic > zwitterionic > anionic for CIP, which resembled the Kd of single
      solute sorption. Fourier transform infrared spectroscopy (FT-IR) spectra
      indicated that amine in SDZ and keto oxygen in CIP were responsible for the
      interactions with the montmorillonite and kaolinite.

PMID- 29598155
TI  - Two Are No Different Than One: Ureteral Duplication Appears to Have No Effect on
      Ureteroscopy Outcomes.
AB  - INTRODUCTION: Ureteral duplication is the most common ureteral anomaly, occurring
      in 0.6%-0.7% of the population. Our objective was to compare urolithiasis
      treatment outcomes in patients with and without ureteral duplication. METHODS:
      Patients with ureteral duplication who underwent ureteroscopy (URS) were
      identified in a stone registry at a high-volume, tertiary care center from 1998
      to 2015. Preoperative, intraoperative, and postoperative data were collected
      retrospectively. A 1:1 control cohort of patients without duplication was
      identified, matched by stone location and size, as well as age, body mass index
      (BMI), and gender. Clinical data and outcomes were compared between duplication
      and control groups, between partial and complete duplication groups, and between
      patients in whom duplication was identified intraoperatively vs known
      preoperatively. RESULTS: Fifty patients with ureteral duplication who underwent
      URS were identified and were matched to 50 control patients. Patients with
      ureteral duplication required longer operative time (55 minutes vs 38.5 minutes,
      p = 0.022). Ureteral duplication had no effect on stone-free rates or need for
      additional procedures. High-grade (Clavien 4-5) complications were similar in
      both groups (4% vs 4%). Location of ureteral duplication and preoperative
      knowledge of ureteral duplication did not affect operative time or stone-free
      rates. CONCLUSIONS: Patients with ureteral duplication undergoing URS for urinary
      stone disease have longer operative times. Preoperative knowledge of ureteral
      duplication appears to have no significant effect on URS's safety or efficacy. In
      patients without a prior diagnosis of ureteral duplication, our data suggest that
      intraoperative detection via endoscopy and fluoroscopy is sufficient to safely
      and completely treat stone disease.

PMID- 29598224
TI  - Integrating Spiritual Care During Interprofessional Simulation for Baccalaureate
      Nursing Students.
AB  - Interprofessional educational experiences for baccalaureate nursing students are
      essential to prepare them for interprofessional communication and collaborative
      interprofessional teamwork. The aim of this descriptive qualitative study was to
      understand the experience of baccalaureate nursing students utilizing the
      hospital chaplain while caring for a suicidal patient in the emergency department
      during simulation. The need for interprofessional education is documented in the
      literature, but there are very few comprehensive, successful projects integrating
      spiritual care for nurse educators to use as models. This project can serve as a
      model of a successful interprofessional education initiative involving
      preprofessional nursing students and chaplain services. Overall, nursing students
      found the learning experience to be beneficial in preparation for professional
      practice on a collaborative interprofessional health care team.

PMID- 29598225
TI  - A Qualitative Study of a Compassion, Presence, and Resilience Training for
      Oncology Interprofessional Teams.
AB  - The well-being of health care providers may be challenged by their work, with
      evidence that oncology health care providers are a high-risk group for burnout.
      The present qualitative pilot study evaluated a mindfulness-based group
      intervention, referred to as Compassion, Presence, and Resilience Training (CPR
      T), for oncology interprofessional teams. The purpose of this study was to
      elucidate the subjective experience of oncology health care providers receiving
      CPR-T and their perceptions of its benefits, risks, or challenges. The CPR-T was
      delivered to providers from two oncology teams in a large cancer center in
      Canada. Ten of these providers participated in semistructured interviews 1 to 5
      months after completing the CPR-T. The interview transcripts were coded using a
      thematic analysis strategy. Five benefits of the CPR-T were identified: learning
      to pause, acquiring a working definition of stress and self-care, becoming fully
      present, building self-compassion, and receiving organizational acknowledgment
      and recognition of stress. In addition, two participant-identified challenges
      were recognized: sharing vulnerability within interprofessional teams and
      committing to a sitting meditation practice. These findings demonstrate positive
      transformations as a result of the CPR-T, as well as important challenges, and
      have important implications for holistic health care practice in oncology.
      Further research is necessary to validate the findings of this explorative study.

PMID- 29598432
TI  - Childhood Trauma and Psychopathic Features Among Juvenile Offenders.
AB  - Despite growing interest in psychopathic personality features in juvenile
      offenders, few studies have examined the relationship between childhood trauma
      and psychopathy. The present study utilized two datasets: 253 adolescents in a
      residential facility for juvenile offenders in Pennsylvania and 723
      institutionalized delinquents in Missouri. Zero-order correlations and linear
      regression techniques were employed for boys and girls to examine the
      relationships between trauma, assessed using the Massachusetts Youth Screening
      Instrument Version 2 (MAYSI-2) Traumatic Experiences Scale and the Childhood
      Trauma Questionnaire (CTQ), and psychopathy as measured by the Youth Psychopathic
      Traits Inventory (YPI) and the Psychopathic Personality Inventory-Short Form (PPI
      SF). Results indicate that psychopathy is significantly correlated with childhood
      trauma. For the Missouri data, trauma significantly predicted psychopathy scores
      for both boys and girls. These results suggest that nuanced understanding of
      traumatic history of these adolescents may not only be a pathway to psychopathy
      but also a critical part of their overall assessment and treatment plan.

PMID- 29598451
TI  - Novel drug discovery strategies for atherosclerosis that target necrosis and
      necroptosis.
AB  - INTRODUCTION: Formation and enlargement of a necrotic core play a pivotal role in
      atherogenesis. Since the discovery of necroptosis, which is a regulated form of
      necrosis, prevention of necrotic cell death has become an attractive therapeutic
      goal to reduce plaque formation. Areas covered: This review highlights the
      triggers and consequences of (unregulated) necrosis and necroptosis in
      atherosclerosis. The authors discuss different pharmacological strategies to
      inhibit necrotic cell death in advanced atherosclerotic plaques. Expert opinion:
      Addition of a necrosis or necroptosis inhibitor to standard statin therapy could
      be a promising strategy for primary prevention of cardiovascular disease.
      However, a necrosis inhibitor cannot block all necrosis stimuli in
      atherosclerotic plaques. A necroptosis inhibitor could be more effective, because
      necroptosis is mediated by specific proteins, termed receptor-interacting
      serine/threonine-protein kinases (RIPK) and mixed lineage kinase domain-like
      pseudokinase (MLKL). Currently, only RIPK1 inhibitors have been successfully used
      in atherosclerotic mouse models to inhibit necroptosis. However, because RIPK1 is
      involved in both necroptosis and apoptosis, and also RIPK1-independent
      necroptosis can occur, we feel that targeting RIPK3 and MLKL could be a more
      attractive therapeutic approach to inhibit necroptosis. Therefore, future
      challenges will consist of developing RIPK3 and MLKL inhibitors applicable in
      both preclinical and clinical settings.

PMID- 29598751
TI  - Threat Bias and Emotion Recognition in Victims of IPV.
AB  - Although there is growing evidence of the association between threat bias and
      psychopathology in many trauma-exposed populations, there are few studies with
      intimate partner violence (IPV) victims. The present study assessed threat bias
      in IPV victims. It also examined potential differences in facial recognition
      ability between victims and nonvictims. Participants were 153 female college
      students currently in a dating relationship. Participants completed demographic
      and abuse severity measures. They then completed a dot-probe task to assess
      threat bias, and a facial expression recognition task to assess speed and
      accuracy of recognition. Approximately 32% of the students sampled were currently
      in a physically abusive relationship. Results indicated that IPV victims had a
      bias toward fearful faces, and showed worse recognition of happy faces than
      nonvictims. These data suggest that the psychological impact of threat bias might
      vary temporally. Vigilance during threat may serve as a protective mechanism,
      whereas postthreat vigilance might be associated with psychopathology.
      Researchers should carefully consider the presence of threat bias in victim
      samples and include other victim groups in future assessments of threat bias. It
      will be important to test these relationships in other IPV victim samples, such
      as help-seeking victims and other community living victims.

PMID- 29598452
TI  - Proteobacteria and Bacteroidetes are major phyla of filterable bacteria passing
      through 0.22 MUm pore size membrane filter, in Lake Sanaru, Hamamatsu, Japan.
AB  - 141 filterable bacteria that passed through a 0.22 MUm pore size filter were
      isolated from Lake Sanaru in Hamamatsu, Japan. These belonged to Proteobacteria,
      Bacteroidetes, Firmicutes, or Actinobacteria among which the first two phyla
      comprised the majority of the isolates. 48 isolates (12 taxa) are candidates
      assignable to new bacterial species or genera of Proteobacteria or Bacteroidetes.

PMID- 29598691
TI  - Intrauterine Hyperglycemia Is Associated with an Impaired Postnatal Response to
      Oxidative Damage.
AB  - Hyperglycemia and other adverse exposures early in life that reprogram stem cells
      may lead to long-lasting phenotypic influences over the lifetime of an
      individual. Hyperglycemia and oxidative stress cause DNA damage when they exceed
      the protective capabilities of the cell, in turn affecting cellular function. DNA
      damage in response to hyperglycemia and oxidative stress was studied in human
      umbilical cord mesenchymal stem cells (hUC-MSCs) from large-for-gestational-age
      (LGA) infants of mothers with gestational diabetes mellitus (LGA-GDM) and control
      subjects. We tested the response of these cells to hyperglycemia and oxidative
      stress, measuring reactive oxygen species (ROS) levels and antioxidant enzyme
      activities. We find that hUC-MSCs from LGA-GDM infants have increased DNA damage
      when exposed to oxidative stress. With the addition of hyperglycemic conditions,
      these cells have an increase in ROS and a decrease in antioxidant glutathione
      peroxidase (GPx) activity, indicating a mechanism for the increased ROS and DNA
      damage. This study demonstrates that a memory of in utero hyperglycemia, mediated
      through downregulation of GPx activity, leads to an increased susceptibility to
      oxidative stress. The alteration of GPx function in self-renewing stem cells, can
      mediate the effect of intrauterine hyperglycemia to be propagated into adulthood
      and contribute to disease susceptibility.

PMID- 29598752
TI  - A Neglected Population: Media Consumption, Perceived Risk, and Fear of Crime
      Among International Students.
AB  - The 4.5 million international students worldwide bring in multifold benefits to
      the advancement of culture, economy, and national security in education host
      countries. Surprisingly, few prior studies have explored international students'
      fear of crime, which may harm their mental and physical health and undermine
      their educational achievements. The current study aims to fill in this research
      void by investigating international students' fear of crime in line with the
      cultivation theoretical framework, which postulates that media consumption
      cultivates fear of crime. The analyses draw on a sample of 398 international
      students attending nine different public and private universities across the
      United States. Using structural equation modeling (SEM), I investigate the extent
      and correlates of students' fear of crime. The findings reveal that international
      students are more fearful in the United States than in their home countries. SEM
      results show that controlling for students' fear in their home countries,
      attention paid to crime news is positively related to fear in the United States,
      through perceived victimization risk. The SEM results also suggest that exposure
      to non-U.S. social media (e.g., WeChat and Weibo) is positively related to
      respondents' fear of crime, whereas exposure to U.S. social media (e.g., Facebook
      and Twitter) is not related to fear of crime. The current study highlights the
      importance of studying the impact of fear of crime and social media use on
      international students.

PMID- 29598769
TI  - Revisiting the Housing-Health Relationship for HIV-Positive Persons: Qualitative
      Evidence From the Lower Manya Krobo District, Ghana.
AB  - The relationship between housing and HIV infection is complex. On one hand, poor
      housing arrangements may affect the health of persons living with HIV/AIDS
      (PLWHAs). On the other hand, PLWHAs may be more likely to live in substandard
      homes because of their health. We used qualitative in-depth individual interviews
      of 38 PLWHAs attending voluntary counseling services at two government hospitals
      in the Lower Manya Krobo District (LMKD) in the Eastern region of Ghana to
      examine their housing and health outcomes. Results show that the majority of
      PLWHAs lived in homes that lacked basic amenities, were overcrowded, had
      structural deficiencies, and were noisy and dirty. They suffered from poor
      housing conditions mainly because of their HIV serostatus, as this affected their
      ability to finance adequate homes, while HIV-related stigmatization led to
      eviction from either family homes or rented facilities.

PMID- 29598770
TI  - Living a Life Full of Pain: Older Pain Clinic Patients' Experience of Living With
      Chronic Low Back Pain.
AB  - Chronic low back pain (CLBP) is older adults' most common pain complaint and is
      associated with many physical and psychosocial consequences, which have been
      quantitatively examined. However, little research has qualitatively examined the
      experience itself of CLBP in later life. Study objective was to understand older
      adults' lived CLBP experience. Guided by van Manen's phenomenological method, 21
      pain clinic patients aged 66 to 83 completed semistructured interviews. Under the
      main theme "living a life full of pain," results are reflected in four
      existential subthemes: (a) Corporeality: The pain is relentless and constantly
      monitored, (b) Temporality: To live with pain is to live by pacing day and night,
      (c) Relationality: Pain creates limits that can be tested or obeyed, and (d)
      Spatiality: Manipulating the space around me to accommodate the pain. Findings
      improve understanding of the patient experience of late life CLBP and highlights
      the importance of empathy and patient-centeredness when treating older adults.

PMID- 29598788
TI  - Gene silencing of heparanase results in suppression of invasion and migration of
      gallbladder carcinoma cells.
AB  - This study investigated the effect of transcriptional gene silencing of the
      heparanase gene on standard gallbladder carcinoma cells (GBC-SD). The miRNAs
      targeting the promoter region and coding region of the heparanase gene were
      designed and synthesized. We transfected four recombinant miRNA vectors into GBC
      SD. We performed the wound healing assays and invasion assays. The result shows
      that the heparanase expression was significantly decreased by recombinant vectors
      in transfected GBC-SD cells (p < 0.01), of which pmiR-Hpa-2 showed best
      interference effect (p < 0.05). The penetrated and migrating cells numbers and
      adherence rate of GBC-SD cells were significantly decreased by pmiR-Hpa-2 (p <
      0.05).

PMID- 29598807
TI  - The Affordable Care Act and the Faltering Revolution in Behavioral Health Care.
AB  - Often described in such terms as a "revolution" and a "game-changer" for the
      behavioral health sector in the United States, the Affordable Care Act has helped
      to enhance coverage for mental health and substance use disorders while
      encouraging service system innovations at the organizational level. However, tens
      of millions of Americans still lack health insurance, insurance companies are
      resisting the implementation of parity coverage rules, and inequalities in the
      financing and organization of care continue to worsen in key respects. This
      article examines these difficulties and their political-economic nature,
      highlighting the need for a single-payer framework if the task of reform is to be
      fulfilled.

PMID- 29598808
TI  - "With Great Power Comes Great Responsibility": Democracy, the Secretary of State
      for Health and Blame Shifting Within the English National Health Service.
AB  - The English National Health Service (NHS) has suffered from a democratic deficit
      since its inception. Democratic accountability was to be through ministers to
      Parliament, but ministerial control over and responsibility for the NHS were
      regarded as myths. Reorganizations and management and market reforms, in the
      neoliberal era, have centralized power within the NHS. However, successive
      governments have sought to reduce their responsibility for health care through
      institutional depoliticization, to shift blame, facilitated through legal
      changes. New Labour's creation of the National Institute for Clinical Excellence
      (NICE) and Monitor were somewhat successful in reducing ministerial culpability
      regarding health technology regulation and foundation trusts, respectively. The
      Conservative-Liberal Democrat coalition created NHS England to reduce ministerial
      culpability for health care more generally. This is pertinent as the NHS is
      currently being undermined by inadequate funding and privatization. However, the
      public has not shifted from blaming the government to blaming NHS England. This
      indicates limits to the capacity of law to legitimize changes to social
      relations. While market reforms were justified on the basis of empowering
      patients, I argue that addressing the democratic deficit is a preferable means of
      achieving this goal.

PMID- 29598809
TI  - The Price of Demanding Peace: The Case of Academics for Peace in Turkey.
AB  - Escalation of violence resulted with more violence in 2015 in Turkey. Two hundred
      and sixty-eight officially confirmed round-the-clock (all day long) and/or open
      ended curfews in 11 cities and at least 47 districts of Turkey have occurred.
      1,809,000 residents, and the fundamental rights of these people have been
      explicitly violated. On January 11, 2016, 1,128 academics signed a petition and
      made a declaration. Immediately after the declaration witch hunt started. This
      report aims to display the case of Academics for Peace Petition.

PMID- 29598810
TI  - Patterns of Health Care Utilization for Noncommunicable Diseases in a
      Transitional European Country: Results From the National Health Survey.
AB  - This study aimed to assess possible differences in health services utilization
      among people living with noncommunicable diseases (NCDs) in the Republic of
      Srpska (RS), Bosnia and Herzegovina, with special reference to NCD
      multimorbidity. In addition, the relationship between self-perceived health and
      health care utilization was assessed. Data were retrieved from the 2010 National
      Health Survey. A cross-sectional study design was used. A total of 4,673 persons
      aged 18 years and older were identified in the households, of which 4,128 were
      interviewed. Logistic regression analyses were used to estimate the effects of
      NCDs on health care utilization in RS. Respondents with NCD multimorbidity more
      frequently visited family physicians (odds ratio [OR], 2.74; 95% confidence
      interval [CI], 2.34 - 3.19), dentists (OR, 1.57; CI, 1.28 - 1.92), private
      doctors (OR, 2.14; CI, 1.74 - 2.64), and urgent care departments (OR, 2.30; CI,
      1.75 - 3.03) than their counterparts without NCDs. They also had more hospital
      admissions (OR, 2.03; CI, 1.56 - 2.64). This is the first study to address the
      relationship between health care utilization and NCDs in the population of RS.
      Further research is needed to explore how best to organize health care to meet
      the needs of people in RS with NCDs, especially with NCD multimorbidity.

PMID- 29598811
TI  - Physical characteristics and resistance parameters of typical urban cyclists.
AB  - This study investigates the rolling and drag resistance parameters and bicycle
      and cargo masses of typical urban cyclists. These factors are important for
      modelling of cyclist speed, power and energy expenditure, with applications
      including exercise performance, health and safety assessments and transportation
      network analysis. However, representative values for diverse urban travellers
      have not been established. Resistance parameters were measured utilizing a field
      coast-down test for 557 intercepted cyclists in Vancouver, Canada. Masses were
      also measured, along with other bicycle attributes such as tire pressure and
      size. The average (standard deviation) of coefficient of rolling resistance,
      effective frontal area, bicycle plus cargo mass, and bicycle-only mass were
      0.0077 (0.0036), 0.559 (0.170) m2, 18.3 (4.1) kg, and 13.7 (3.3) kg,
      respectively. The range of measured values is wider and higher than suggested in
      existing literature, which focusses on sport cyclists. Significant correlations
      are identified between resistance parameters and rider and bicycle attributes,
      indicating higher resistance parameters for less sport-oriented cyclists. The
      findings of this study are important for appropriately characterising the full
      range of urban cyclists, including commuters and casual riders.

PMID- 29598812
TI  - Preface.

PMID- 29598813
TI  - Editorial: The Need of Time: Development of New Antimicrobials.

PMID- 29598814
TI  - Editorial: Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis:
      An Epidemic that will Boost the Incidence of Cardiovascular Morbidity and
      Mortality.

PMID- 29598815
TI  - Determinants of childhood diarrhea in Medebay Zana District, Northwest Tigray,
      Ethiopia: a community based unmatched case-control study.
AB  - BACKGROUND: Globally, childhood diarrhea is amongst the most prevalent health
      problems and accounts for 9% of all deaths in children under-five. In Ethiopia,
      childhood diarrhea is a major public health problem in which the prevalence
      ranges from 13.5 to 30.5% and experienced by multiple factors. Although health
      extension program has been implementing for couples of years; diarrheal disease
      remains the second cause of morbidity and continues an important public health
      problem in the study district. Thus, this study assessed determinants of
      diarrheal disease among under-five children in the Medebay Zana district,
      northwest Tigray, Ethiopia, 2015. METHOD: A community based case-control study
      was used. A multistage sampling procedure was employed to enroll the study
      participants. Data were collected using face to face administered questionnaire.
      The collected data were entered into Epi Info version 3.5.4 and exported to SPSS
      Version 21 for analysis. Frequencies with percentages were computed using
      univariate analysis. Finally, logistic regression model was fitted to identify
      factors associated with childhood diarrhea where P-values of less than 0.05 were
      considered statistically significant. RESULTS: Socio-demographic factors such as
      low maternal educational level [AOR = 2.88, 95% CI (1.70, 4.88)], being index
      child of older age, households with >=3 number of children under-five [AOR =
      4.05, 95% CI (1.91, 8.60)] and maternal history of diarrhea [AOR = 2.10, 95% CI
      (1.09, 4.05)] were statistically associated with childhood diarrhea. This study
      also revealed that child feeding practice; not exclusively breastfed [AOR = 4.84,
      95% CI (2.21, 10.60)] and initiation of complementary feeding above 6 months [AOR
      = 1.78, 95% CI (1.09, 2.92)] were statistically associated with outcome variable.
      Environmental and behavioral practices such as unavailability toilet facility
      [AOR = 2.10, 95% CI (1.34, 3.30)], improper solid waste disposal [AOR = 2.29, 95%
      CI (1.53, 3.44)] and unprotected drinking water [AOR = 1.83, 95% CI (1.12, 2.98)]
      were also found significant factors of childhood diarrhea. CONCLUSION: Maternal
      educational status, age of index child, number of < 5 children, child feeding
      practices, maternal history of diarrhea, toilet facility, solid waste disposal
      and household drinking water were found determinants of childhood diarrhea. These
      findings have policy implications and insight the strengthening for health
      intervention programs.

PMID- 29598817
TI  - Hepatitis B in Moroccan-Dutch: a quantitative study into determinants of
      screening participation.
AB  - BACKGROUND: In November 2016, the Dutch Health Council recommended hepatitis B
      (HBV) screening for first-generation immigrants from HBV endemic countries.
      However, these communities show relatively low attendance rates for screening
      programmes, and our knowledge on their participation behaviour is limited. We
      identified determinants associated with the intention to request an HBV screening
      test in first-generation Moroccan-Dutch immigrants. We also investigated the
      influence of non-refundable costs for HBV screening on their intention. METHODS:
      Offline and online questionnaires were distributed among first- and second/third
      generation Moroccan-Dutch immigrants using respondent-driven sampling. Random
      forest analyses were conducted to determine which determinants had the greatest
      impact on (1) the intention to request an HBV screening test on one's own
      initiative, and (2) the intention to participate in non-refundable HBV screening
      at ?70,-. RESULTS: Of the 379 Moroccan-Dutch respondents, 49.3% intended to
      request a test on their own initiative, and 44.1% were willing to attend non
      refundable screening for ?70,-. Clarity regarding infection status, not having
      symptoms, fatalism, perceived self-efficacy, and perceived risk of having HBV
      were the strongest predictors to request a test. Shame and stigma, fatalism,
      perceived burden of screening participation, and social influence of Islamic
      religious leaders had the greatest predictive value for not intending to
      participate in screening at ?70,- non-refundable costs. Perceived severity and
      possible health benefit were facilitators for this intention measure. These
      predictions were satisfyingly accurate, as the random forest method retrieved
      area under the curve scores of 0.72 for intention to request a test and 0.67 for
      intention to participate in screening at ?70,- non-refundable costs. CONCLUSIONS:
      By the use of respondent-driven sampling, we succeeded in studying screening
      behaviour among a hard-to-reach minority population. Despite the limitations
      associated with correlated data and the sampling method, we recommend to (1)
      incorporate clarity regarding HBV status, (2) stress the risk of an asymptomatic
      infection, (3) emphasise mother-to-child transmission as the main transmission
      route, and (4) team up with Islamic religious leaders to help decrease elements
      of fatalism, shame, and stigma to enhance screening uptake of Moroccan immigrants
      in the Netherlands.

PMID- 29598816
TI  - Annexin A2-mediated cancer progression and therapeutic resistance in
      nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a head and neck cancer with poor clinical
      outcomes and insufficient treatments in Southeast Asian populations. Although
      concurrent chemoradiotherapy has improved recovery rates of patients, poor
      overall survival and low efficacy are still critical problems. To improve the
      therapeutic efficacy, we focused on a tumor-associated protein called Annexin A2
      (ANXA2). This review summarizes the mechanisms by which ANXA2 promotes cancer
      progression (e.g., proliferation, migration, the epithelial-mesenchymal
      transition, invasion, and cancer stem cell formation) and therapeutic resistance
      (e.g., radiotherapy, chemotherapy, and immunotherapy). These mechanisms gave us a
      deeper understanding of the molecular aspects of cancer progression, and further
      provided us with a great opportunity to overcome therapeutic resistance of NPC
      and other cancers with high ANXA2 expression by developing this prospective ANXA2
      targeted therapy.

PMID- 29598818
TI  - Signal peptides for recombinant protein secretion in bacterial expression
      systems.
AB  - The secretion of biotechnologically or pharmaceutically relevant recombinant
      proteins into the culture supernatant of a bacterial expression host greatly
      facilitates their downstream processing and significantly reduces the production
      costs. The first step during the secretion of a desired target protein into the
      growth medium is its transport across the cytoplasmic membrane. In bacteria, two
      major export pathways, the general secretion or Sec pathway and the twin-arginine
      translocation or Tat pathway, exist for the transport of proteins across the
      plasma membrane. The routing into one of these alternative protein export systems
      requires the fusion of a Sec- or Tat-specific signal peptide to the amino
      terminal end of the desired target protein. Since signal peptides, besides being
      required for the targeting to and membrane translocation by the respective
      protein translocases, also have additional influences on the biosynthesis, the
      folding kinetics, and the stability of the respective target proteins, it is not
      possible so far to predict in advance which signal peptide will perform best in
      the context of a given target protein and a given bacterial expression host. As
      outlined in this review, the most promising way to find the optimal signal
      peptide for a desired protein is to screen the largest possible diversity of
      signal peptides, either generated by signal peptide variation using large signal
      peptide libraries or, alternatively, by optimization of a given signal peptide
      using site-directed or random mutagenesis strategies.

PMID- 29598819
TI  - HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients.
AB  - BACKGROUND: Diabetic complications may be associated with impaired time-dependent
      glycemic control. Therefore, long-term glycemic variability, assessed by
      variations in haemoglobin A1c (HbA1c), may be a potential risk factor for
      microvascular complications, such as diabetic peripheral neuropathy (DPN). We
      investigated the association of HbA1c variability with DPN in patients with type
      2 diabetes. METHODS: In this cross-sectional study, 563 type 2 diabetic patients
      who had been screened for DPN and undergone quarterly HbA1c measurements during
      the year preceding enrolment were recruited. DPN was confirmed in patients
      displaying both clinical manifestations of neuropathy and abnormalities in a
      nerve conduction evaluation. HbA1c variability was assessed by the coefficient of
      variation of HbA1c (CV-HbA1c), and the mean of HbA1c (M-HbA1c) was calculated. In
      addition, medical history and clinical data were collected. RESULTS: Among the
      recruited patients, 18.1% (n = 102) were found to have DPN, and these patients
      also presented with a higher CV-HbA1c than the patients without DPN (p < 0.001).
      The proportion of patients with DPN increased significantly from 6.9% in the
      first to 19.1% in the second and 28.5% in the third tertile of CV-HbA1c (p for
      trend < 0.001). After adjusting for initial HbA1c, M-HbA1c and other clinical
      factors via multiple logistic regression analysis, the odds ratios (ORs) for DPN
      in the second and third versus those in the first CV-HbA1c tertile were 3.61 (95%
      CI 1.62-8.04) and 6.48 (2.86-14.72), respectively. The area under the receiver
      operating characteristic (ROC) curve of CV-HbA1c was larger than that of M-HbA1c,
      at 0.711 (95% CI 0.659-0.763) and 0.662 (0.604-0.721), respectively. ROC analysis
      also revealed that the optimal cutoff value of CV-HbA1c to indicate DPN was
      15.15%, and its corresponding sensitivity and specificity were 66.67% and 65.73%,
      respectively. CONCLUSIONS: Increased HbA1c variability is closely associated with
      DPN in type 2 diabetic patients and could be considered as a potent indicator for
      DPN in these patients.

PMID- 29598820
TI  - The role of obesity in carotid plaque instability: interaction with age, gender,
      and cardiovascular risk factors.
AB  - BACKGROUND: In the last decade, several studies have reported an unexpected and
      seemingly paradoxical inverse correlation between BMI and incidence of
      cardiovascular diseases. This so called "obesity paradox effect" has been mainly
      investigated through imaging methods instead of histologic evaluation, which is
      still the best method to study the instability of carotid plaque. Therefore, the
      purpose of our study was to evaluate by histology the role of obesity in
      destabilization of carotid plaques and the interaction with age, gender and other
      major cerebrovascular risk factors. METHODS: A total of 390 carotid plaques from
      symptomatic and asymptomatic patients submitted to endarterectomy, for whom
      complete clinical and laboratory assessment of major cardiovascular risk factors
      was available, were studied by histology. Patients with a BMI >= 30.0 kg/m2 were
      considered as obese. Data were analyzed by multivariate logistic regression and
      for each variable in the equation the estimated odds ratio (OR) was calculated.
      RESULTS: Unstable carotid plaque OR for obese patients with age < 70 years was
      5.91 (95% CI 1.17-29.80), thus being the highest OR compared to that of other
      risk factors. Unstable carotid plaque OR decreased to 4.61 (95% CI 0.54-39.19) in
      males >= 70 years, being only 0.93 (95% CI 0.25-3.52) among women. When obesity
      featured among metabolic syndrome risk factors, the OR for plaque destabilization
      was 3.97 (95% CI 1.81-6.22), a significantly higher value compared to OR in non
      obese individuals with metabolic syndrome (OR = 1.48; 95% CI 0.86-2.31). Similar
      results were obtained when assessing the occurrence of acute cerebrovascular
      symptoms. CONCLUSIONS: Results from our study appear to do not confirm any
      paradoxical effect of obesity on the carotid artery district. Conversely, obesity
      is confirmed to be an independent risk factor for carotid plaque destabilization,
      particularly in males aged < 70 years, significantly increasing such risk among
      patients with metabolic syndrome.

PMID- 29598821
TI  - Association between the DNA methylations of POMC, MC4R, and HNF4A and metabolic
      profiles in the blood of children aged 7-9 years.
AB  - BACKGROUND: Proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), and
      hepatocyte nuclear factor 4 alpha (HNF4A) are closely associated with weight gain
      and metabolic traits. In a previous study, we demonstrated associations between
      the methylations of POMC, MC4R, and HNF4A and metabolic profiles at birth.
      However, little is known about these associations in obese children. To evaluate
      the clinical utility of epigenetic biomarkers, we investigated to determine
      whether an association exists between the methylations of POMC, MC4R, and HNF4A
      and metabolic profiles in blood of normal weight and overweight and obese
      children. METHODS: We selected 79 normal weight children and 41 overweight and
      obese children aged 7-9 years in the Ewha Birth and Growth Cohort study. POMC
      methylation levels at exon 3, and MC4R and HNF4A methylation levels in promoter
      regions were measured by pyrosequencing. Serum glucose, total cholesterol (TC),
      triglyceride, high-density lipoprotein cholesterol (HDL-c), and insulin levels
      were analyzed using a biochemical analyzer and an immunoradiometric assay.
      Partial correlation and multiple regression analysis were used to assess
      relationships between POMC, MC4R, and HNF4A methylation levels and metabolic
      profiles. RESULTS: Significant correlations were found between POMC methylation
      and HDL-c levels, and between HNF4A methylation and both TC and HDL-c levels.
      Interestingly, associations were found between POMC methylation status and HDL-c
      levels, and between HNF4A methylation status and TC levels independent of body
      mass index. CONCLUSIONS: These findings show that POMC, MC4R, and HNF4A
      methylation status in the blood of children are associated with metabolic
      profiles. Therefore, we suggest that the DNA methylation status might serve as a
      potential epigenetic biomarkers of metabolic syndrome.

PMID- 29598822
TI  - Dimethyl fumarate attenuates reactive microglia and long-term memory deficits
      following systemic immune challenge.
AB  - BACKGROUND: Systemic inflammation is associated with increased cognitive decline
      and risk for Alzheimer's disease. Microglia (MG) activated during systemic
      inflammation can cause exaggerated neuroinflammatory responses and trigger
      progressive neurodegeneration. Dimethyl fumarate (DMF) is a FDA-approved therapy
      for multiple sclerosis. The immunomodulatory and anti-oxidant properties of DMF
      prompted us to investigate whether DMF has translational potential for the
      treatment of cognitive impairment associated with systemic inflammation. METHODS:
      Primary murine MG cultures were stimulated with lipopolysaccharide (LPS) in the
      absence or presence of DMF. MG cultured from nuclear factor (erythroid-derived 2)
      like 2-deficient (Nrf2 -/- ) mice were used to examine mechanisms of DMF actions.
      Conditioned media generated from LPS-primed MG were used to treat hippocampal
      neuron cultures. Adult C57BL/6 and Nrf2 -/- mice were subjected to peripheral LPS
      challenge. Acute neuroinflammation, long-term memory function, and reactive
      astrogliosis were examined to assess therapeutic effects of DMF. RESULTS: DMF
      suppressed inflammatory activation of MG induced by LPS. DMF suppressed NF-kappaB
      activity through Nrf2-depedent and Nrf2-independent mechanisms in MG. DMF
      treatment reduced MG-mediated toxicity towards neurons. DMF suppressed brain
      derived inflammatory cytokines in mice following peripheral LPS challenge. The
      suppressive effect of DMF on neuroinflammation was blunted in Nrf2 -/- mice.
      Importantly, DMF treatment alleviated long-term memory deficits and sustained
      reactive astrogliosis induced by peripheral LPS challenge. DMF might mitigate
      neurotoxic astrocytes associated with neuroinflammation. CONCLUSIONS: DMF
      treatment might protect neurons against toxic microenvironments produced by
      reactive MG and astrocytes associated with systemic inflammation.

PMID- 29598823
TI  - Full-length mRNA sequencing uncovers a widespread coupling between transcription
      initiation and mRNA processing.
AB  - BACKGROUND: The multifaceted control of gene expression requires tight
      coordination of regulatory mechanisms at transcriptional and post-transcriptional
      level. Here, we studied the interdependence of transcription initiation, splicing
      and polyadenylation events on single mRNA molecules by full-length mRNA
      sequencing. RESULTS: In MCF-7 breast cancer cells, we find 2700 genes with
      interdependent alternative transcription initiation, splicing and polyadenylation
      events, both in proximal and distant parts of mRNA molecules, including examples
      of coupling between transcription start sites and polyadenylation sites. The
      analysis of three human primary tissues (brain, heart and liver) reveals similar
      patterns of interdependency between transcription initiation and mRNA processing
      events. We predict thousands of novel open reading frames from full-length mRNA
      sequences and obtained evidence for their translation by shotgun proteomics. The
      mapping database rescues 358 previously unassigned peptides and improves the
      assignment of others. By recognizing sample-specific amino-acid changes and novel
      splicing patterns, full-length mRNA sequencing improves proteogenomics analysis
      of MCF-7 cells. CONCLUSIONS: Our findings demonstrate that our understanding of
      transcriptome complexity is far from complete and provides a basis to reveal
      largely unresolved mechanisms that coordinate transcription initiation and mRNA
      processing.

PMID- 29598824
TI  - An integrated community health worker intervention in rural Nepal: a type 2
      hybrid effectiveness-implementation study protocol.
AB  - BACKGROUND: Evidence-based medicines, technologies, and protocols exist to
      prevent many of the annual 300,000 maternal, 2.7 million neonatal, and 9 million
      child deaths, but they are not being effectively implemented and utilized in
      rural areas. Nepal, one of South Asia's poorest countries with over 80% of its
      population living in rural areas, exemplifies this challenge. Community health
      workers are an important cadre in low-income countries where human resources for
      health and health care infrastructure are limited. As local women, they are
      uniquely positioned to understand and successfully navigate barriers to health
      care access. Recent case studies of large community health worker programs have
      highlighted the importance of training, both initial and ongoing, and
      accountability through structured management, salaries, and ongoing monitoring
      and evaluation. A gap in the evidence regarding whether such community health
      worker systems can change health outcomes, as well as be sustainably adopted at
      scale, remains. In this study, we plan to evaluate a community health worker
      system delivering an evidence-based integrated reproductive, maternal, newborn,
      and child health intervention as it is scaled up in rural Nepal. METHODS: We will
      conduct a type 2 hybrid effectiveness-implementation study to test both the
      effect of an integrated reproductive, maternal, newborn, and child health
      intervention and the implementation process via a professional community health
      worker system. The intervention integrates five evidence-based approaches: (1)
      home-based antenatal care and post-natal care counseling and care coordination;
      (2) continuous surveillance of all reproductive age women, pregnancies, and
      children under age 2 years via a mobile application; (3) Community-Based
      Integrated Management of Newborn and Childhood Illness; (4) group antenatal and
      postnatal care; and 5) the Balanced Counseling Strategy to post-partum
      contraception. We will evaluate effectiveness using a pre-post quasi-experimental
      design with stepped implementation and implementation using the RE-AIM framework.
      DISCUSSION: This is the first hybrid effectiveness-implementation study of an
      integrated reproductive, maternal, newborn, and child health intervention in
      rural Nepal that we are aware of. As Nepal takes steps towards achieving the
      Sustainable Development Goals, the data from this three-year study will be useful
      in the detailed planning of a professionalized community health worker cadre
      delivering evidence-based reproductive, maternal, newborn, and child health
      interventions to the country's rural population. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT03371186 , registered 04 December 2017,
      retrospectively registered.

PMID- 29598825
TI  - Combined flow cytometry and high-throughput image analysis for the study of
      essential genes in Caenorhabditis elegans.
AB  - BACKGROUND: Advances in automated image-based microscopy platforms coupled with
      high-throughput liquid workflows have facilitated the design of large-scale
      screens utilising multicellular model organisms such as Caenorhabditis elegans to
      identify genetic interactions, therapeutic drugs or disease modifiers. However,
      the analysis of essential genes has lagged behind because lethal or sterile
      mutations pose a bottleneck for high-throughput approaches, and a systematic way
      to analyse genetic interactions of essential genes in multicellular organisms has
      been lacking. RESULTS: In C. elegans, non-conditional lethal mutations can be
      maintained in heterozygosity using chromosome balancers, commonly expressing
      green fluorescent protein (GFP) in the pharynx. However, gene expression or
      function is typically monitored by the use of fluorescent reporters marked with
      the same fluorophore, presenting a challenge to sort worm populations of
      interest, particularly at early larval stages. Here, we develop a sorting
      strategy capable of selecting homozygous mutants carrying a GFP stress reporter
      from GFP-balanced animals at the second larval stage. Because sorting is not
      completely error-free, we develop an automated high-throughput image analysis
      protocol that identifies and discards animals carrying the chromosome balancer.
      We demonstrate the experimental usefulness of combining sorting of homozygous
      lethal mutants and automated image analysis in a functional genomic RNA
      interference (RNAi) screen for genes that genetically interact with mitochondrial
      prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous
      PHB deletion mutants develop into sterile adults due to maternal contribution and
      strongly induce the mitochondrial unfolded protein response (UPRmt). In a
      chromosome-wide RNAi screen for C. elegans genes having human orthologues, we
      uncover both known and new PHB genetic interactors affecting the UPRmt and
      growth. CONCLUSIONS: The method presented here allows the study of balanced
      lethal mutations in a high-throughput manner. It can be easily adapted depending
      on the user's requirements and should serve as a useful resource for the C.
      elegans community for probing new biological aspects of essential nematode genes
      as well as the generation of more comprehensive genetic networks.

PMID- 29598826
TI  - The complexity of titin splicing pattern in human adult skeletal muscles.
AB  - BACKGROUND: Mutations in the titin gene (TTN) cause a large spectrum of diseases
      affecting skeletal and/or cardiac muscle. TTN includes 363 coding exons, a
      repeated region with a high degree of complexity, isoform-specific elements, and
      metatranscript-only exons thought to be expressed only during fetal development.
      Although three main classes of isoforms have been described so far, alternative
      splicing events (ASEs) in different tissues or in different developmental and
      physiological states have been reported. METHODS: To achieve a comprehensive view
      of titin ASEs in adult human skeletal muscles, we performed a RNA-Sequencing
      experiment on 42 human biopsies collected from 12 anatomically different skeletal
      muscles of 11 individuals without any skeletal-muscle disorders. RESULTS: We
      confirmed that the skeletal muscle N2A isoforms are highly prevalent, but we
      found an elevated number of alternative splicing events, some at a very high
      level. These include previously unknown exon skipping events and alternative 5'
      and 3' splice sites. Our data suggests the partial inclusion in the TTN
      transcript of some metatranscript-only exons and the partial exclusion of
      canonical N2A exons. CONCLUSIONS: This study provides an extensive picture of the
      complex TTN splicing pattern in human adult skeletal muscle, which is crucial for
      a proper clinical interpretation of TTN variants.

PMID- 29598828
TI  - The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA
      turnover globally.
AB  - BACKGROUND: Eukaryotic transcription is regulated through two complexes, the
      general transcription factor IID (TFIID) and the coactivator Spt-Ada-Gcn5
      acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA
      contribute to the synthesis of nearly all transcripts and are recruited genome
      wide in yeast. However, how this broad recruitment confers selectivity under
      specific conditions remains an open question. RESULTS: Here we find that the
      SAGA/TREX-2 subunit Sus1 associates with upstream regulatory regions of many
      yeast genes and that heat shock drastically changes Sus1 binding. While Sus1
      binding to TFIID-dominated genes is not affected by temperature, its recruitment
      to SAGA-dominated genes and RP genes is significantly disturbed under heat shock,
      with Sus1 relocated to environmental stress-responsive genes in these conditions.
      Moreover, in contrast to recent results showing that SAGA deubiquitinating enzyme
      Ubp8 is dispensable for RNA synthesis, genomic run-on experiments demonstrate
      that Sus1 contributes to synthesis and stability of a wide range of transcripts.
      CONCLUSIONS: Our study provides support for a model in which SAGA/TREX-2 factor
      Sus1 acts as a global transcriptional regulator in yeast but has differential
      activity at yeast genes as a function of their transcription rate or during
      stress conditions.

PMID- 29598827
TI  - Integrated biology approach reveals molecular and pathological interactions among
      Alzheimer's Abeta42, Tau, TREM2, and TYROBP in Drosophila models.
AB  - BACKGROUND: Cerebral amyloidosis, neuroinflammation, and tauopathy are key
      features of Alzheimer's disease (AD), but interactions among these features
      remain poorly understood. Our previous multiscale molecular network models of AD
      revealed TYROBP as a key driver of an immune- and microglia-specific network that
      was robustly associated with AD pathophysiology. Recent genetic studies of AD
      further identified pathogenic mutations in both TREM2 and TYROBP. METHODS: In
      this study, we systematically examined molecular and pathological interactions
      among Abeta, tau, TREM2, and TYROBP by integrating signatures from transgenic
      Drosophila models of AD and transcriptome-wide gene co-expression networks from
      two human AD cohorts. RESULTS: Glial expression of TREM2/TYROBP exacerbated tau
      mediated neurodegeneration and synergistically affected pathways underlying late
      onset AD pathology, while neuronal Abeta42 and glial TREM2/TYROBP synergistically
      altered expression of the genes in synaptic function and immune modules in AD.
      CONCLUSIONS: The comprehensive pathological and molecular data generated through
      this study strongly validate the causal role of TREM2/TYROBP in driving molecular
      networks in AD and AD-related phenotypes in flies.

PMID- 29598829
TI  - Depletion of DNMT1 in differentiated human cells highlights key classes of
      sensitive genes and an interplay with polycomb repression.
AB  - BACKGROUND: DNA methylation plays a vital role in the cell, but loss-of-function
      mutations of the maintenance methyltransferase DNMT1 in normal human cells are
      lethal, precluding target identification, and existing hypomorphic lines are
      tumour cells. We generated instead a hypomorphic series in normal hTERT
      immortalised fibroblasts using stably integrated short hairpin RNA. RESULTS:
      Approximately two-thirds of sites showed demethylation as expected, with one
      third showing hypermethylation, and targets were shared between the three
      independently derived lines. Enrichment analysis indicated significant losses at
      promoters and gene bodies with four gene classes most affected: (1)
      protocadherins, which are key to neural cell identity; (2) genes involved in fat
      homoeostasis/body mass determination; (3) olfactory receptors and (4)
      cancer/testis antigen (CTA) genes. Overall effects on transcription were
      relatively small in these fibroblasts, but CTA genes showed robust derepression.
      Comparison with siRNA-treated cells indicated that shRNA lines show substantial
      remethylation over time. Regions showing persistent hypomethylation in the shRNA
      lines were associated with polycomb repression and were derepressed on addition
      of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was, in
      contrast, associated with poised promoters. CONCLUSIONS: We have assessed for the
      first time the effects of chronic depletion of DNMT1 in an untransformed,
      differentiated human cell type. Our results suggest polycomb marking blocks
      remethylation and indicate the sensitivity of key neural, adipose and cancer
      associated genes to loss of maintenance methylation activity.

PMID- 29598830
TI  - The putative amino acid ABC transporter substrate-binding protein AapJ2 is
      necessary for Brucella virulence at the early stage of infection in a mouse
      model.
AB  - Brucellosis is a zoonotic bacterial disease caused by Brucella spp. The virulence
      of these bacteria is dependent on their ability to invade and replicate within
      host cells. In a previous study, a putative gene bab_RS27735 encoding an amino
      acid ABC transporter substrate-binding protein homologous to AapJ protein was
      found to be involved in Brucella abortus virulence. In this study, we
      successfully constructed a bab_RS27735 deletion mutant, Delta27735. Compared with
      the wild-type strain, the lipopolysaccharide pattern of the mutant was not
      changed, but the growth ability was slightly defected in the exponential phase.
      In tolerance tests, sensitivity of the Delta27735 mutant to oxidative stress,
      bactericidal peptides or low pH was not different from that of the wild-type
      strain. Cell infection assay showed that the mutant was reduced survival within
      macrophages but could efficiently escape lysosome degradation. The results of a
      virulence test showed that the Delta27735 mutant was attenuated in a mouse model
      at the early stage of infection but recovered its virulence at the late stage of
      infection. Meanwhile, the development of splenomegaly and histopathological
      lesions was observed in mice infected with either the wild-type strain or the
      mutant. These results are in line with the release of IL-12p40 and TNF-alpha into
      the peripheral blood of infected mice. Besides, expression of diverse genes was
      up-regulated in the Delta27735 mutant, which may contribute to the reduced
      virulence of the mutant. These data elucidated that the bab_RS27735 gene is
      necessary for B. abortus virulence at the early stage of infection in a mouse
      model.

PMID- 29598832
TI  - Guideline on cochlear implants.
AB  - INTRODUCTION: In the last decade numerous hospitals have started to work with
      patients who are candidates for a cochlear implant (CI) and there have been
      numerous and relevant advances in the treatment of sensorineural hearing loss
      that extended the indications for cochlear implants. OBJECTIVES: To provide a
      guideline on cochlear implants to specialists in otorhinolaryngology, other
      medical specialities, health authorities and society in general. METHODS: The
      Scientific Committees of Otology, Otoneurology and Audiology from the Spanish
      Society of Otolaryngology and Head and Neck Surgery (SEORL-CCC), in a coordinated
      and agreed way, performed a review of the current state of CI based on the
      existing regulations and in the scientific publications referenced in the
      bibliography of the document drafted. RESULTS: The clinical guideline on cochlear
      implants provides information on: a) Definition and description of Cochlear
      Implant; b) Indications for cochlear implants; c) Organizational requirements for
      a cochlear implant programme. CONCLUSIONS: A clinical guideline on cochlear
      implants has been developed by a Committee of Experts of the SEORL-CCC, to help
      and guide all the health professionals involved in this field of CI in decision
      making to treathearing impairment.

PMID- 29598833
TI  - It's time for a change of message, it's time for #GunSafetyNow.

PMID- 29598835
TI  - Why validation of prognostic models matters?
AB  - Prognostic models are powerful tools for treatment personalisation. However, not
      all proposed models work well when validated using new data, despite impressive
      results being reported initially. Here, we will use a hands-on approach to
      highlight important aspects of prognostic modelling, as well as to demonstrate
      methods to generate generalisable models.

PMID- 29598831
TI  - Smoking under hypoxic conditions: a potent environmental risk factor for
      inflammatory and autoimmune diseases.
AB  - Autoimmune disease management presents a significant challenge to medical
      science. Environmental factors potentially increase the risk of developing
      inflammatory and autoimmune diseases, such as multiple sclerosis, rheumatoid
      arthritis, and lupus. Among various environmental stresses, cigarette smoke and
      hypoxia have both been reported to lead to an enhanced risk of inflammatory and
      autoimmune diseases.In this review, we shed light on all reported mechanisms
      whereby cigarette smoke and a hypoxic environment can induce inflammatory and
      autoimmune diseases and discuss how hypoxic conditions influence the cigarette
      smoke-induced threat of inflammatory and autoimmune disease development.Cigarette
      smoke and hypoxia both lead to increased oxidative stress and production of
      reactive oxygen species and other free radicals, which have various effects
      including the generation of autoreactive pro-inflammatory T cells and
      autoantibodies, reductions in T regulatory (Treg) cell activity, and enhanced
      expression of pro-inflammatory mediators [e.g., interleukin-6 (IL-6), interleukin
      4 (IL-4) and interleukin-8 (IL-8)]. Accordingly, smoking and hypoxic environments
      may synergistically act as potent environmental risk factors for inflammatory and
      autoimmune diseases. To our knowledge, no studies have reported the direct
      association of cigarette smoke and hypoxic environments with the risk of
      developing inflammatory and autoimmune diseases.Future studies exploring the risk
      of autoimmune disease development in smokers at high altitudes, particularly
      military personnel and mountaineers who are not acclimatized to high-altitude
      regions, are required to obtain a better understanding of disease risk as well as
      its management.

PMID- 29598836
TI  - Effects of personality functioning on the global functioning of patients with
      bipolar disorder I.
AB  - Due to the comorbidity of personality traits or disorders and BD, the present
      study investigated the extent to which the global functioning of patients with BD
      would be affected by personality functioning. This study included 100 subsequent
      patients who had been diagnosed with BD-I, and were in the remission phase.
      Global functioning was assessed with the Bipolar Disorder Functioning
      Questionnaire (BDFQ) and the Level of Personality Functioning Scale (LPFS) was
      conducted following psychodynamic-oriented semi-structured interviews to assess
      the level of personality functioning. Hierarchical linear regression models were
      conducted. After controlling other variables, the predictability of LPFS
      components on global functionality was assessed. Global functioning was
      negatively correlated with subsyndromal depressive symptoms, the presence of a
      psychiatric comorbidity, alcohol/substance use disorders, the side effects of
      medication, poor social support, and an impaired level of personality
      functioning. Finally, a decrease in the level of personality functioning
      predicted impaired global functioning. The present study demonstrated that the
      level of personality functioning had a significant impact on global functioning
      during the euthymic period of BD. Therefore, the assessment of the level of
      personality functioning in patients with BD will aid in better understanding this
      population and in the design of long-term treatment plans.

PMID- 29598834
TI  - Clinical outcome after high-precision radiotherapy for skull base meningiomas:
      Pooled data from three large German centers for radiation oncology.
AB  - PURPOSE: To evaluate outcome in patients with base of skull meningiomas treated
      with modern high precision radiation therapy (RT) techniques. PATIENTS AND
      METHODS: 927 patients from three centers were treated with either radiosurgery or
      fractionated high-precision RT for meningiomas. Treatment planning was based on
      CT and MRI following institutional guidelines. For radiosurgery, a median dose of
      13 Gy was applied, for fractionated treatments, a median dose of 54 Gy in 1.8 Gy
      single fractions was prescribed. Follow-up included a clinical examination as
      well as contrast-enhanced imaging. All patients were followed up prospectively
      after radiotherapy in the three departments within a strict follow-up regimen.
      The median follow-up time was 81 months (range 1-348 months). RESULTS: Median
      local control was 79 months (range 1-348 months). Local control (LC) was 98% at 1
      year, 94% at 3 years, 92% at 5 years and 86% at 10 years. There was no difference
      between radiosurgery and fractionated RT. We analyzed the influence of higher
      doses on LC and could show that dose did not impact LC. Moreover, there was no
      difference between 54 Gy and 57.6 Gy in the fractionated group. Side effects were
      below 5% in both groups without any severe treatment-related complications.
      DISCUSSION: Based on the pooled data analysis this manuscript provides a large
      series of meningiomas of the skull base treated with modern high precision RT
      demonstrating excellent local control and low rates of side effects. Such data
      support the recommendation of RT for skull base meningiomas in the
      interdisciplinary tumor board discussions. The strong role of RT must influence
      treatment recommendations keeping in mind the individual risk-benefit profile of
      treatment alternatives.

PMID- 29598837
TI  - Effects of cochlear synaptopathy on middle-ear muscle reflexes in unanesthetized
      mice.
AB  - Cochlear synaptopathy, i.e. the loss of auditory-nerve connections with cochlear
      hair cells, is seen in aging, noise damage, and other types of acquired
      sensorineural hearing loss. Because the subset of auditory-nerve fibers with high
      thresholds and low spontaneous rates (SRs) is disproportionately affected,
      audiometric thresholds are relatively insensitive to this primary neural
      degeneration. Although suprathreshold amplitudes of wave I of the auditory
      brainstem response (ABR) are attenuated in synaptopathic mice, there is not yet a
      robust diagnostic in humans. The middle-ear muscle reflex (MEMR) might be a
      sensitive metric (Valero et al., 2016), because low-SR fibers may be important
      drivers of the MEMR (Liberman and Kiang, 1984; Kobler et al., 1992). Here, to
      test the hypothesis that narrowband reflex elicitors can identify synaptopathic
      cochlear regions, we measured reflex growth functions in unanesthetized mice with
      varying degrees of noise-induced synaptopathy and in unexposed controls. To
      separate effects of the MEMR from those of the medial olivocochlear reflex, the
      other sound-evoked cochlear feedback loop, we used a mutant mouse strain with
      deletion of the acetylcholine receptor required for olivocochlear function. We
      demonstrate that the MEMR is normal when activated from non-synaptopathic
      cochlear regions, is greatly weakened in synaptopathic regions, and is a more
      sensitive indicator of moderate synaptopathy than the suprathreshold amplitude of
      ABR wave I.

PMID- 29598838
TI  - Hidden hearing loss and endbulbs of Held: Evidence for central pathology before
      detection of ABR threshold increases.
AB  - Reductions in sound-evoked activity in the auditory nerve due to hearing loss
      have been shown to cause pathological changes in central auditory structures.
      Hearing loss due strictly to the aging process are less well documented. In this
      study of CBA/CaH mice, we provide evidence for age-related pathology in the
      endbulb of Held, a large axosomatic ending arising from myelinated auditory nerve
      fibers. Endbulbs are known to be involved in the processing of temporal cues used
      for sound localization and speech comprehension. Hearing thresholds as measured
      by auditory brainstem response (ABR) thresholds remained stable up to one year,
      whereas suprathreshold amplitudes of early ABR waves decreased by up to 50% in
      older mice, similar to that reported for age-related cochlear synaptopathy
      (Sergeyenko et al., 2013). The reduction of ABR response magnitude with age
      correlated closely in time with the gradual atrophy of endbulbs of Held, and is
      consistent with the hypothesis that endbulb integrity is dependent upon normal
      levels of spike activity in the auditory nerve. These results indicate that
      central auditory pathologies emerge as consequence of so-called "hidden" hearing
      loss and suggest that such brain changes require consideration when devising
      therapeutic interventions.

PMID- 29598839
TI  - Auditory and audio-vocal responses of single neurons in the monkey ventral
      premotor cortex.
AB  - Monkey vocalization is a complex behavioral pattern, which is flexibly used in
      audio-vocal communication. A recently proposed dual neural network model suggests
      that cognitive control might be involved in this behavior, originating from a
      frontal cortical network in the prefrontal cortex and mediated via projections
      from the rostral portion of the ventral premotor cortex (PMvr) and motor cortex
      to the primary vocal motor network in the brainstem. For the rapid adjustment of
      vocal output to external acoustic events, strong interconnections between vocal
      motor and auditory sites are needed, which are present at cortical and
      subcortical levels. However, the role of the PMvr in audio-vocal integration
      processes remains unclear. In the present study, single neurons in the PMvr were
      recorded in rhesus monkeys (Macaca mulatta) while volitionally producing
      vocalizations in a visual detection task or passively listening to monkey
      vocalizations. Ten percent of randomly selected neurons in the PMvr modulated
      their discharge rate in response to acoustic stimulation with species-specific
      calls. More than four-fifths of these auditory neurons showed an additional
      modulation of their discharge rates either before and/or during the monkeys'
      motor production of the vocalization. Based on these audio-vocal interactions,
      the PMvr might be well positioned to mediate higher order auditory processing
      with cognitive control of the vocal motor output to the primary vocal motor
      network. Such audio-vocal integration processes in the premotor cortex might
      constitute a precursor for the evolution of complex learned audio-vocal
      integration systems, ultimately giving rise to human speech.

PMID- 29598840
TI  - Emergency Tracheal Intubation in an Ankylosing Spondylitis Patient in a Sitting
      Position Using an Airway Scope Combined with Face-to-Face and Digital Intubation.
AB  - BACKGROUND: Emergency intubation in a patient with advanced ankylosing
      spondylitis (AS) who presents with severe thoracic kyphosis deformity, rigid
      cervical flexion deformity of the neck, and an inability to achieve the supine
      position is particularly challenging to emergency physicians. CASE REPORT: This
      study reports on an AS patient presenting with these difficult airway
      characteristics and acute respiratory failure who was successfully intubated
      using video laryngoscope-assisted inverse intubation (II) and blind digital
      intubation (BDI). By using Pentax AirwayScope-assisted inverse intubation, the
      tracheal tube tip was passed through the glottic opening, but an unexpected
      resistance occurred during tube advancement, which was overcome by subsequent
      BDI. By using laryngoscope-assisted II complemented by the BDI technique, the
      patient was successfully intubated without complications. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Our case demonstrated that these two emergency
      airway management techniques are valuable backup methods and complement each
      other when applied to certain unstable airways, especially when the traditional
      patient position is not easily accomplished. Unexpected difficulty is not rare
      during airway management; emergency physicians should always be well prepared
      both mentally and practically.

PMID- 29598841
TI  - Narrow width of muscle-preserving selective laminectomy demonstrated sufficient
      surgical outcomes and reduced surgical invasiveness.
AB  - Sufficient width of laminectomy or laminoplasty is considered a criterion for
      successful surgical outcomes following posterior cervical decompression. No
      previous study has focused on surgical outcomes achieved by wide versus narrow
      decompression. This study examined whether narrow laminectomy width (LW) affected
      surgical outcomes in cervical compressive myelopathy (CCM). Between 2005 and
      2010, we performed muscle-preserving selective laminectomy (SL) with
      decompression between the bilateral medial margin of the facet joints (wide SL).
      After 2010, we began to perform narrow SL, in which the LW was no more than 2-3
      mm wider than the spinal cord width (SW). Clinical features and radiological
      findings from 97 CCM patients in whom SL was performed at two consecutive levels,
      including the C4/5 level, were examined in this study. The relationship between
      LW and patients' functional outcomes was analyzed. Mean blood loss was lower in
      the narrow SL group than in the wide SL group. The length of hospital stay was
      also shorter in the narrow SL group. The wide SL group showed greater posterior
      spinal cord shift. The incidence of C5 palsy correlated with LW and LW minus SW
      (LW-SW). The recovery rate (RR) of Japanese Orthopaedic Association score was
      comparable between the two groups. The RR was not correlated with LW and LW-SW.
      Sufficient functional recovery can be achieved by narrow SL, and it offers
      advantages over wide posterior decompression, including reduced surgical
      invasiveness and complications. Wide decompression width is not always necessary
      for CCM patients.

PMID- 29598842
TI  - Comparison of tramadol/acetaminophen fixed-dose combination, tramadol, and
      acetaminophen in patients undergoing ambulatory arthroscopic meniscectomy.
AB  - OBJECTIVES: Preemptive analgesia is a technique in which analgesics are
      administered before a surgery to provide better postoperative pain relief with
      fewer side effects. In this study, we aimed to compare the preemptive efficacy of
      tramadol/acetaminophen fixed-dose combination, tramadol, and acetaminophen in
      patients undergoing ambulatory arthroscopic partial meniscectomy. METHODS: We
      evaluated the patient records of 75 patients who underwent ambulatory
      arthroscopic partial meniscectomy. We divided the patients into three groups
      consisting of 20 patients each to equalize the groups. Group A comprised patients
      who were administered 37.5 mg tramadol/325 mg acetaminophen fixed-dose
      combination, Group B comprised patients who were administered 50 mg tramadol, and
      Group C comprised patients who were administered 500 mg acetaminophen.
      Premedication was not used in any group. RESULTS: There were no significant
      differences between the groups in terms of age, sex, BMI, and duration of surgery
      and anesthesia. All patients in Group B and Group C and 17 patients in Group A
      required rescue analgesics in the first 6 h. Visual analog scale (VAS) was 4.75
      +/- 3.05 in Group B at time 0 and was 6.10 +/- 1.86 in Group C in the first hour
      and was higher than the other groups with a statistically significance (p = 0.030
      and 0.020, respectively). VAS at 24 h postoperatively was <=3 (1.60 +/- 1.63,
      1.55 +/- 1.84 and 1.70 +/- 0.65 respectively in each group), and none of the
      patients in any group required rescue analgesics. No major side effects, except
      for slight nausea in one patient requiring no medication, were noted in any
      group. CONCLUSION: The fixed-dose combination of tramadol/acetaminophen or
      tramadol alone is better than acetaminophen alone as a preemptive analgesic in
      patients undergoing ambulatory arthroscopic meniscectomy. LEVEL OF EVIDENCE:
      Level III, therapeutic study.

PMID- 29598843
TI  - Treatment outcome of dome osteotomy of the pelvis combined with trochanteric
      advancement for sequelae of Perthes' disease.
AB  - OBJECTIVE: Disparity in size between femoral head and acetabulum could promote
      premature degeneration of the hip joint. The purpose of this study was to report
      the results of Kawamura's dome osteotomy for acetabular dysplasia due to sequelae
      of Perthes' disease. PATIENTS AND METHODS: Fourteen patients (14 hips) operated
      between 1999 and 2012 were retrospectively reviewed. There were 9 males and 5
      females with a mean age of 29 years (range, 15-54 years). Functional and
      radiological results were reviewed at mean follow-up of 9 years (range, 4-12
      years). RESULTS: Pain relief was obtained in 13 of 14 (92.8%) patients
      postoperatively. Good to excellent functional outcome was obtained in 10 of 14
      (71.4%) patients. Mean Harris hip score was improved from 63 to 84 (p < 0.05) at
      the final follow-up. Improvement of limping gait was observed in 10 of 14 (71.4%)
      patients. Center edge angle improved from mean 24 degrees  (11-36 degrees )
      preoperatively to mean 35 degrees  (27-46 degrees ) postoperatively (p < 0.05),
      acetabular angle improved from mean 43 degrees  (36-49 degrees ) preoperatively
      to mean 37 degrees  (32-44 degrees ) postoperatively (p < 0.05), acetabular head
      index improved from mean 69% (50-83%) preoperatively to mean 85% (73-100%)
      postoperatively (p < 0.05). Progression of arthrosis stage occurred in 3 of 14
      (21%) patients. None of the hip with preoperative Stulberg III, 2 of 9 hips with
      Stulberg IV and 2 of 2 hips with Stulberg V needed conversion to total hip
      arthroplasty during the follow-up. CONCLUSION: Dome osteotomy of the pelvis
      combined with trochanteric advancement could give a reasonable treatment outcome
      for acetabular dysplasia due to Perthes' disease at mid to long-term follow-up.
      Advanced stage of arthrosis, preoperative Stulberg V and no improvement of
      limping gait after the surgery possibly associated with poor outcome. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 29598844
TI  - Effect of BMI on outcomes of surgical treatment for tibial plateau fractures: A
      comparative retrospective case series study.
AB  - PURPOSE: Tibia plateau fracture (TPF) treatment aims at achieving a stable,
      aligned, mobile, painless knee and preventing post-traumatic osteoarthritis. To
      achieve this goal, surgeons consider criteria such as patients' characteristics,
      severity, risk of complications, fracture displacement/depression, degree of soft
      tissue injury. However, body mass index (BMI) is not considered as a risk factor
      in literature. Our study was conducted to find out any possible correlation
      between BMI and functional scores or radiological score separately. METHODS:
      Retrospective analysis of case series between 2011 and 2014 was done on the
      database of a tertiary hospital in Istanbul. There were 67 TPF patients (54
      males, 13 females) in the study. Relationship between BMI and functional knee
      scores or radiological score was compared statistically. Closed fractures with
      both high-energy and low-energy injury were included in the study. Patients with
      open fracture, multi-trauma presence, meniscus and/or ligamentous injury,
      increased co-morbidity, inadequate records (25 cases in all) were excluded.
      Surgery type, Schatzker classification, injury side, trauma energy, and gender
      were considered as possible risk factors. Binary regression analysis was done for
      possible factors affecting functional knee scores and radiologic score. RESULTS:
      Model summary calculations were done as Nagelkerke R2 test for Knee Society
      score, Lysholm knee score, and Ahlback and Rydberg radiologic scores, which were
      0.648, 0.831, and 0.327 respectively. Homer-Lemeshow test values were 0.976,
      0.998, and 0.362, respectively. There is negative correlation between BMI and
      both knee function scores. There is no correlation between BMI and radiologic
      score. CONCLUSION: An increase in BMI has a negative effect on functional knee
      scores after surgical treatment of TPFs. Therefore, BMI should be considered as a
      risk factor for surgical treatment of TPFs.

PMID- 29598845
TI  - Urinary parabens and triclosan concentrations and associated exposure
      characteristics in a Korean population-A comparison between night-time and first
      morning urine.
AB  - Parabens and triclosan have been widely used in many personal care products and
      cosmetics. The endocrine disrupting potential of these compounds is of increasing
      public health concern. The aim of this study is to understand the current
      exposure profile of these chemicals in last void before bedtime (night-time) and
      first-morning void (first-morning) urines among a Korean population and to
      characterize their exposure sources and pathways. A total of 261 people,
      including infants (0-2 years), toddlers (3-6 years), children (7-12 years),
      adolescents (13-18 years), and adults (>=19 years), were recruited, and sampled
      for night-time urine and first-morning urine of the following day. Methyl (MeP),
      ethyl (EtP), propyl (PrP) and butyl paraben (BuP), and triclosan were measured in
      urine. The demographic characteristics, use of personal care products, and food
      consumption were obtained through a questionnaire. Among the target compounds,
      EtP and MeP were most frequently detected at the highest concentrations. The
      median concentration of EtP in night-time urine was 32.4 MUg/L (interquartile
      range: 8.37-82.8 MUg/L), which is higher than previously reported worldwide.
      Unlike other test compounds, compared to those measured from first-morning urine,
      the EtP concentrations were significantly higher in night-time urine, suggesting
      the presence of different exposure sources. Among adults, the MeP and PrP
      concentrations in night-time urine were associated with frequent use of skin care
      products, colored cosmetics, bath products, toothpaste, vinyl food packaging, or
      consumption of canned food. The MeP and PrP concentrations were higher in females
      than in males, especially in night-time urine. The results of this study also
      show that multiple urine samples are necessary to capture the diurnal variation
      of non-occupational exposure to environmental chemicals, such as parabens.

PMID- 29598846
TI  - The role of mitochondrial activity in female fertility and assisted reproductive
      technologies: overview and current insights.
AB  - Mitochondria have been implicated as key factors regulating female reproductive
      processes. Notable progress has been made in determining the role of mitochondria
      with respect to oocyte maturation, fertilization and early embryo development. In
      addition, mitochondrial function and dysfunction has been the subject of various
      studies in ovarian ageing and metabolic stress models. However, the overall
      mitochondrial impact on female fertility is yet to be uncovered. The
      mitochondrial DNA content of granulosa, cumulus and trophectoderm cells is being
      explored as a biomarker of oocyte quality and embryo viability. As growing
      evidence suggests that embryo potential could be related to the ability of oocyte
      mitochondria to generate energy, efforts have been made to investigate the
      possibility of improving mitochondrial capacity in women with poor outcomes after
      treatment with assistedreproductive technologies. Thus far, therapeutic attempts
      have focused mainly on using nutrients to restore mitochondrial function and
      transferring mitochondria from autologous germline precursor cells. Moreover, new
      perspectives on optimizing infertility treatments have arisen with modern
      mitochondrial replacement therapies, which are being applied in women with
      mitochondrial disease-causing mutations. This review explores aspects of the
      distinctive contribution of mitochondria to reproductive processes and discusses
      current and emerging clinical implications.

PMID- 29598847
TI  - Impact of androgen supplementation on the follicular endocrine milieu in women
      with hypoandrogenism.

PMID- 29598848
TI  - Dual Transforming Growth Factor-beta and Programmed Death-1 Blockade: A Strategy
      for Immune-Excluded Tumors?
AB  - Tumors that elude infiltration by CD8+ T lymphocytes are particularly resistant
      to multiple forms of treatment, including immune checkpoint blockade. Stromal
      transforming growth factor (TGF)-beta appears to play a key role in this process,
      potentially constituting a target for novel combinatorial regimens tackling
      immune-excluded neoplasms.

PMID- 29598849
TI  - Duodenal repair with a jejunal pedicle graft.

PMID- 29598852
TI  - Editorial overview: Preventive and therapeutic vaccines.

PMID- 29598850
TI  - Evaluation of risk factors for complications after bariatric surgery.
AB  - The decision to perform a bariatric surgical procedure, the conclusion of a
      clinical pathway in which management is individually adapted to each patient, is
      taken after multidisciplinary consultation. Paradoxically, the patients who would
      most benefit from surgery are also those who have the highest operative risk. In
      practice, predictive factors of mortality and severe postoperative complications
      (Clavien-Dindo>III) must be used to evaluate the benefit/risk ratio most
      objectively. The main risk factors are age, male gender, body mass index,
      obstructive sleep apnea syndrome, insulin resistance and diabetes, tobacco abuse,
      cardiovascular disease, ability to lose weight before surgery, hypoalbuminemia
      and functional disability. Routine preoperative evaluation of high perioperative
      risk patients provides the attending physician with information to: (1) correct
      several of these risk factors before surgery and thereby limit the operative
      risk; (2) orient the patient to a less risky surgical procedure and/or to a
      facility with a more adapted technical capacity, as necessary; (3) contra
      indicate the operation if the risks exceed the expected benefits. All in all,
      this preoperative evaluation combined with management of comorbidities
      contributes to decrease the risk of postoperative complications and to improve
      the overall management of obese patients.

PMID- 29598851
TI  - First Magnetic Resonance Managed by a Cardiology Department in the Spanish Public
      Healthcare System. Experience and Difficulties of an Innovative Model.
AB  - Magnetic resonance (MR) is considered the gold standard in the assessment of
      myocardial morphology, function, perfusion, and viability. However, its main
      limitation is its scarce availability. In 2014, we installed the first MR scanner
      exclusively managed by a cardiology department within the publicly-funded Spanish
      healthcare system with the aim of improving patient-care, training and research
      in the department. In the time interval analyzed, July 2014 to May 2017, 3422
      cardiac MR scans were performed (32minutes used per study; 96% with good quality;
      75% with contrast media administration). The most prevalent clinical indications
      were cardiomyopathy (29%) and ischemic heart disease (12%). Twenty-five percent
      of studies were conducted in the context of research protocols. Follow-up studies
      predominated among outpatients, while pretherapeutic assessment was more common
      in hospitalized patients. The presumptive diagnosis was changed by cardiac MR
      scanning in up to 20% of patients investigated for ischemic heart disease. The
      installation and operative management of an MR scanner in our cardiology
      department has allowed us to integrate this technique into daily clinical
      practice, modify our clinical protocols, optimize access to this technology among
      cardiac patients, improve training, and conduct clinical research.

PMID- 29598853
TI  - Simultaneous influence of indigenous microorganism along with abiotic factors
      controlling arsenic mobilization in Brahmaputra floodplain, India.
AB  - In the dynamic cycling of oxic and anoxic aqueous alluvial aquifer environments,
      varying Arsenic (As) concentrations are controlled by both abiotic and biotic
      factors. Studies have shown a significant form of toxic As (III) being released
      through the reductive dissolution of iron-oxy/hydroxide minerals and microbial
      reduction mechanisms, which leads to a serious health concern. The present study
      was performed in order to assess the abiotic and biotic factors influencing As
      release into the alluvial aquifer groundwater in Brahmaputra floodplain, India.
      The groundwater chemistry, characterization of the sediments, isolation,
      identification and characterization of prominent As releasing indigenous
      bacterium were conducted. The measured solid and liquid phases of total As
      concentration were ranged between 0.02 and 17.2 mg kg-1 and 8 to 353 MUg L-1,
      respectively. The morphology and mineralogy showed the presence of detrital and
      authigenic mineral assemblages whereas primary and secondary As bearing Realgar
      and Claudetite minerals were identified, respectively. Furthermore, significant
      non-labile As fraction was found associated with the amorphous oxides of Fe, Mn
      and Al. The observed groundwater chemistry and sediment color, deduced a sub-oxic
      reducing aquifer conditions in As-contaminated regions. In addition, 16S rDNA
      sequencing results of the isolated bacterium showed the prominent Pseudomonas
      aeruginosa responsible for the mobilization of As, reducing condition,
      biomineralization and causing grey color to the sediments at the shallower and
      deeper aquifers in the study area. These findings suggest that microbial
      metabolic activities are equally responsible in iron-oxy/hydroxide reductive
      dissolution, controlling As mobilization in dynamic fluvial flood plains.

PMID- 29598854
TI  - Utility of Invasive Electrophysiology Studies in Patients With Severe Aortic
      Stenosis Undergoing Transcatheter Aortic Valve Implantation.
AB  - Permanent pacemaker (PPM) implantation remains common after transcatheter aortic
      valve implantation (TAVI). Invasive electrophysiology studies (EPSs) may reduce
      PPM implantation rates by identifying patients who do not require long-term
      pacing. At our institution, a new strategy in which patients with equivocal
      indications for pacing underwent EPSs to determine the need for PPM implantation
      was adopted. We compared baseline demographics, TAVI procedural details, and
      outcomes in patients without any conduction disturbance after TAVI, patients with
      new PPM implantation, and patients with EPS +/- new PPM implantation. After
      exclusion for preexisting PPMs, of a total of 614 consecutive TAVI patients, 117
      (19.1%) required new PPM implantation for unequivocal pacing indications, and 95
      (15.5%) underwent EPSs. Of those patients who underwent EPSs, 28 (29.5%) required
      PPM implantation and 67 (70.5%) did not. The overall rate of new PPM implantation
      was higher for self-expanding versus balloon-expandable valves (34.0% vs 19.9%, p
      = 0.0011). PPM implantation increased intensive care and hospital length of stay
      compared with patients without any conduction disturbance (10.7 +/- 8.3 vs 8.5 +/
      6.4 days, p = 0.003). A negative EPS did not prolong length of stay. There were
      no significant differences in 30-day and 1-year mortality between groups. In
      conclusion, among TAVI patients with new-onset conduction disturbance, EPS is a
      safe strategy to identify those who require PPM implantation and those in whom
      PPMs can be avoided.

PMID- 29598855
TI  - Role of Percutaneous Coronary Intervention in the Treatment of Cardiac Allograft
      Vasculopathy.
AB  - We evaluated our quarter-century experience with percutaneous coronary
      intervention (PCI) in patients with cardiac allograft vasculopathy (CAV). CAV is
      a progressive form of atherosclerosis that is characterized by diffuse intimal
      thickening. It is a major cause of morbidity and mortality after orthotopic heart
      transplantation (OHT). Effective treatment options are limited. PCI has been used
      as a palliative treatment in selected patients. We retrospectively analyzed 140
      patients with CAV who underwent PCI from 1992 to 2017 at the University of
      California, Los Angeles (UCLA) Medical Center. The primary end point was freedom
      from death, myocardial infarction (MI), target vessel revascularization (TVR),
      and repeat OHT, at a follow-up of 10 years. PCI was unsuccessful in 3 patients
      (2%). Balloon angioplasty (n = 7), bare metal stents (n = 50), or drug-eluting
      stents (DES, n = 80) were used for PCI. Freedom from the primary end point was 17
      +/- 8%. The use of DES did not provide significant benefit for the primary end
      point (23 +/- 14% vs 10 +/- 9%, p = 0.16). Freedom from the individual end points
      was low: death was 43 +/- 10%, MI was 74 +/- 12%, TVR was 54 +/- 12%, and repeat
      OHT was 42 +/- 15%. Freedom from TVR was not significantly different from DES and
      bare metal stent (67 +/- 14% vs 52 +/- 20%, p = 0.46). In conclusion, among
      patients who underwent PCI for CAV, freedom from the composite of death, MI, TVR,
      and repeat OHT was low.

PMID- 29598856
TI  - Lyme Carditis and High-Degree Atrioventricular Block.
AB  - Canada has seen a sixfold increase in Lyme disease since being nationally
      notifiable in 2009. This is the first Canadian series on Lyme carditis manifested
      as high-degree atrioventricular block. We report 5 recent cases presented over a
      2-year period. The variation of nonspecific presentations requires a high index
      of suspicion for prompt diagnosis and correct management. Recognizing this early
      would curtail the progression of conduction disorders and potentially avoid
      permanent pacemaker implantation.

PMID- 29598857
TI  - The Impact of U.S. Free Trade Agreements on Calorie Availability and Obesity: A
      Natural Experiment in Canada.
AB  - INTRODUCTION: Globalization via free trade and investment agreements is often
      implicated in the obesity pandemic. Concerns center on how free trade and
      investment agreements increase population exposure to unhealthy, high-calorie
      diets, but existing studies preclude causal conclusions. Few studies of free
      trade and investment agreements and diets isolated their impact from confounding
      changes, and none examined any effect on caloric intake, despite its critical
      role in the etiology of obesity. This study addresses these limitations by
      analyzing a unique natural experiment arising from the exceptional circumstances
      surrounding the implementation of the 1989 Canada-U.S. Free Trade Agreement.
      METHODS: Data from the UN (2017) were analyzed using fixed-effects regression
      models and the synthetic control method to estimate the impact of the Canada-U.S.
      Free Trade Agreement on calorie availability in Canada, 1978-2006, and coinciding
      increases in U.S. exports and investment in Canada's food and beverage sector.
      The impact of changes to calorie availability on body weights was then modeled.
      RESULTS: Calorie availability increased by ?170 kilocalories per capita per day
      in Canada after the Canada-U.S. Free Trade Agreement. There was a coinciding rise
      in U.S. trade and investment in the Canadian food and beverage sector. This rise
      in calorie availability is estimated to account for an average weight gain of
      between 1.8 kg and 12.2 kg in the Canadian population, depending on sex and
      physical activity levels. CONCLUSIONS: The Canada-U.S. Free Trade Agreement was
      associated with a substantial rise in calorie availability in Canada. U.S. free
      trade and investment agreements can contribute to rising obesity and related
      diseases by pushing up caloric intake.

PMID- 29598858
TI  - Factors Associated With County-Level Differences in U.S. Drug-Related Mortality
      Rates.
AB  - INTRODUCTION: Over the past 2 decades, drug-related deaths have grown to be a
      major U.S. public health problem. County-level differences in drug-related
      mortality rates are large. The relative contributions of social determinants of
      health to this variation, including the economic, social, and healthcare
      environments, are unknown. METHODS: Using data from the U.S. Centers for Disease
      Control and Prevention Multiple-Cause of Death Files (2006-2015, analyzed in
      2017); U.S. Census Bureau; U.S. Department of Agriculture Economic Research
      Service; Agency for Healthcare Research and Quality; and Northeast Regional
      Center for Rural Development, this paper modeled associations between county
      level drug-related mortality rates and economic, social, and healthcare
      environments. Spatial autoregressive models controlled for state fixed effects
      and county demographic characteristics. RESULTS: The average county-level age
      adjusted drug-related mortality rate was 16.6 deaths per 100,000 population (2006
      2015), but there were substantial geographic disparities in rates. Controlling
      for county demographic characteristics, average mortality rates were
      significantly higher in counties with greater economic and family distress and in
      counties economically dependent on mining. Average mortality rates were
      significantly lower in counties with a larger presence of religious
      establishments, a greater percentage of recent in-migrants, and counties with
      economies reliant on public (government) sector employment. Healthcare supply
      factors did not contribute to between-county disparities in mortality rates.
      CONCLUSIONS: Drug-related mortality rates are not randomly distributed across the
      U.S. Future research should consider the specific pathways through which
      economic, social, and healthcare environments are associated with drug-related
      mortality.

PMID- 29598859
TI  - Long-Term Outcomes Following Surgical Aortic Bioprosthesis Implantation.
AB  - BACKGROUND: Few data exist on long-term outcomes and structural valve
      degeneration (SVD) in consecutive unselected patients undergoing surgical aortic
      valve replacement (SAVR). OBJECTIVES: The goal of this study was to determine the
      long-term outcomes of a contemporary cohort of consecutive unselected SAVR
      recipients with a focus on evaluating clinical outcomes and SVD based on
      echocardiographic criteria. METHODS: A total of 672 consecutive patients (mean
      age: 72 +/- 8 years; 61.5% male) undergoing SAVR with a bioprosthesis between
      2002 and 2004 were included. Baseline and follow-up data were prospectively
      collected in a dedicated database. Baseline post-operative echocardiographic data
      were obtained in the 624 patients alive at hospital discharge and in 209 patients
      at 10 years (87% of the patients at risk). SVD was defined as subclinical
      (increase >10 mm Hg in mean transvalvular gradient + decrease >0.3 cm2 in valve
      area and/or new-onset mild or moderate aortic regurgitation) and clinically
      relevant (increase >20 mm Hg in mean transvalvular gradient + decrease >0.6 cm2
      in valve area and/or new-onset moderate-to-severe aortic regurgitation). RESULTS:
      At a median follow-up of 10 years (interquartile range: 5 to 13 years), 432
      patients (64.3%) had died. Older age, left ventricular dysfunction, atrial
      fibrillation, chronic obstructive pulmonary disease, greater body mass index, and
      diabetes mellitus were associated with an increased mortality risk (p < 0.05 for
      all). Clinically relevant SVD occurred in 6.6% of patients; 30.1% of patients had
      subclinical SVD. A greater body mass index and the use of a specific aortic
      bioprosthesis were independently associated with clinically relevant SVD (p <
      0.05 for both), and 83% of these patients underwent aortic valve reintervention
      (valve-in-valve transcatheter aortic valve replacement in 44% of them).
      CONCLUSIONS: The 10-year mortality rate in elderly SAVR recipients of a
      bioprosthetic valve was considerable, chiefly determined by their older age and
      the presence of comorbidities. Clinically relevant SVD was infrequent, but close
      to one third of the population exhibited subclinical SVD. These results provide
      contemporary data on long-term clinical outcomes and SVD post-SAVR, and they
      should be taken into consideration when evaluating late clinical outcomes and
      valve durability after transcatheter aortic valve replacement.

PMID- 29598860
TI  - Aortic Valve Replacement in an Era of Rapid Innovation: Better the Devil You
      Know.

PMID- 29598861
TI  - Rapid Deployment Versus Conventional Bioprosthetic Valve Replacement for Aortic
      Stenosis.
AB  - BACKGROUND: Surgical aortic valve replacement using conventional biological
      valves (CBVs) is the standard of care for treatment of old patients with aortic
      valve disease. Recently, rapid deployment valves (RDVs) have been introduced.
      OBJECTIVES: The purpose of this study was to report the nationwide German
      experience concerning RDVs for treatment of aortic valve stenosis and provide a
      head-to-head comparison with CBVs. METHODS: A total of 22,062 patients who
      underwent isolated surgical aortic valve replacement using CBV or RDV between
      2011 and 2015 were enrolled into the German Aortic Valve Registry. Baseline,
      procedural, and in-hospital outcome parameters were analyzed for CBVs and RDVs
      using 1:1 propensity score matching. Furthermore, 3 RDVs were compared with each
      other. RESULTS: A total of 20,937 patients received a CBV, whereas 1,125 patients
      were treated with an RDV. Patients treated with an RDV presented with
      significantly reduced procedure (160 min [25th to 75th percentile: 135 to 195
      min] vs. 150 min [25th to 75th percentile: 127 to 179 min]; p < 0.001),
      cardiopulmonary bypass (83 min [25th to 75th percentile: 68 to 104 min] vs. 70
      min [25th to 75th percentile: 56 to 87 min]; p < 0.001), and aortic cross clamp
      times (60 min [25th to 75th percentile: 48 to 75 min] vs. 44 min [25th to 75th
      percentile: 35 to 57 min]; p < 0.001), but showed significantly elevated rates of
      pacemaker implantation (3.7% vs. 8.8%; p < 0.001) and disabling stroke (0.9% vs.
      2.2%; p < 0.001), whereas in-hospital mortality was similar (1.7% vs. 2.2%; p =
      0.22). These findings persisted after 1:1 propensity score matching. Comparison
      of the 3 RDVs revealed statistically nonsignificant different pacemaker rates and
      significantly different post-operative transvalvular gradients. CONCLUSIONS: In
      this large, all-comers database, the incidence of pacemaker implantation and
      disabling stroke was higher with RDVs, whereas no beneficial effect on in
      hospital mortality was seen. The 3 RDVs presented different complication profiles
      with regard to pacemaker implantation and transvalvular gradients. (German Aortic
      Valve Registry [GARY]; NCT01165827).

PMID- 29598862
TI  - Sutureless Prostheses for Aortic Valve Replacement: Quicker May Not Be Better.

PMID- 29598863
TI  - Presenting Systolic Blood Pressure and Outcomes in Patients With Acute Aortic
      Dissection.
AB  - BACKGROUND: Presenting systolic blood pressure (SBP) is a powerful predictor of
      mortality in many cardiovascular settings, including acute coronary syndromes,
      cardiogenic shock, and acute heart failure. OBJECTIVES: This study evaluated the
      association of presenting SBP with in-hospital outcomes, specifically all-cause
      mortality, in acute aortic dissection (AAD). METHODS: The study included 6,238
      consecutive patients (4,167 with type A and 2,071 with type B AAD) enrolled in
      the International Registry of Acute Aortic Dissection. Patients were stratified
      in 4 groups according to presenting SBP: SBP >150, SBP 101 to 150, SBP 81 to 100,
      or SBP <=80 mm Hg. RESULTS: The relationship between presenting SBP and in
      hospital mortality displayed a J-curve association, with significantly higher
      mortality rates in patients with very high SBP (26.3% for SBP >180 mm Hg in type
      A AAD, 13.3% for SBP >200 mm Hg in type B AAD; p = 0.005 and p = 0.018,
      respectively) as well as in those with SBP <=100 mm Hg (29.9% in type A, 22.4% in
      type B; p = 0.033 and p = 0.015, respectively). This relationship was mainly from
      increased rates of in-hospital complications (acute renal failure, coma, and
      mesenteric ischemia/infarction in patients with SBP >150 mm Hg; stroke, coma,
      cardiac tamponade, myocardial ischemia/infarction, and acute renal failure in
      patients with SBP <=80 mm Hg). Notably, presenting SBP <=80 mm Hg was
      independently associated with in-hospital mortality in both type A (p = 0.001)
      and type B AAD (p = 0.003). CONCLUSIONS: Presenting SBP showed a clear J-curve
      relationship with in-hospital mortality in patients with AAD. Although this
      association was related to increased rates of comorbid conditions at the edges of
      the curve, SBP <=80 mm Hg was an independent correlate of in-hospital mortality.

PMID- 29598864
TI  - Hypotensive Systolic Blood Pressure Predicts Severe Complications and In-Hospital
      Mortality in Acute Aortic Dissection.

PMID- 29598865
TI  - PET Assessment of Epicardial Intimal Disease and Microvascular Dysfunction in
      Cardiac Allograft Vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of graft
      failure and death after heart transplantation. Absolute myocardial blood flow
      (MBF) quantification using rubidium 82 (Rb-82) positron emission tomography (PET)
      could enable evaluation of diagnostically challenging diffuse epicardial and
      microvascular disease in CAV. OBJECTIVES: The authors aimed to evaluate Rb-82 PET
      detection of CAV. METHODS: Consecutive transplant recipients undergoing coronary
      angiography were prospectively evaluated with PET, multivessel intravascular
      ultrasound (IVUS), and intracoronary hemodynamics. CAV was defined as
      International Society of Heart and Lung Transplantation CAV1-3 on angiography and
      maximal intimal thickness >=0.5 mm on IVUS. RESULTS: Forty patients (mean age 56
      years, 4.8 years post-transplant) completed evaluation. CAV was detected in 32
      patients (80%) by IVUS and 14 (35%) by angiography. PET correlated significantly
      with invasive coronary flow indices: r = 0.29, rate-pressure product-adjusted
      myocardial flow reserve (cMFR) versus coronary flow reserve; r = 0.28, relative
      flow reserve versus fractional flow reserve; and r = 0.37, coronary vascular
      resistance (CVR) versus index of microcirculatory resistance. Patients with CAV
      or microvascular dysfunction had reduced cMFR and stress MBF and increased CVR.
      Receiver operator characteristic curves demonstrated good accuracy of PET for CAV
      on IVUS (area under the curve 0.77 to 0.81) and optimal diagnostic cutoffs of
      cMFR <2.9, stress MBF <2.3, and CVR >55. Combined PET assessment for CAV yielded
      excellent >93% sensitivity (>65% specificity) for 1 abnormal parameter and >96%
      specificity (>55% sensitivity) for 2 abnormal parameters. CONCLUSIONS: Rb-82 PET
      flow quantification has high diagnostic accuracy for CAV, with potential for
      noninvasive evaluation after heart transplantation.

PMID- 29598866
TI  - Functional and Structural Alterations in Cardiac Allograft Vasculopathy.

PMID- 29598868
TI  - Holiday Heart: Some Sobering Mechanistic Insights.

PMID- 29598867
TI  - Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia.
AB  - BACKGROUND: Excessive binge alcohol drinking has acute cardiac arrhythmogenic
      effects, including promotion of atrial fibrillation (AF), which underlies
      "Holiday Heart Syndrome." The mechanism that couples binge alcohol abuse with AF
      susceptibility remains unclear. We previously reported stress-activated c-Jun N
      terminal kinase (JNK) signaling contributes to AF development. This is
      interesting because JNK is implicated in alcohol-caused organ malfunction beyond
      the heart. OBJECTIVES: The purpose of this study was to detail how JNK promotes
      binge alcohol-evoked susceptibility to AF. METHODS: The authors found binge
      alcohol-exposure leads to activated JNK, specifically JNK2. Furthermore, binge
      alcohol induces AF (24- vs. 1.8-Hz burst pacing-induced episodes per attempt per
      animal), higher incidence of diastolic intracellular Ca2+ activity (Ca2+ waves,
      sarcoplasmic reticulum [SR] Ca2+ leakage), and membrane voltage (Vm) and systolic
      Ca2+ release spatiotemporal heterogeneity (DeltatVm-Ca). These changes were
      completely eliminated by JNK inhibition both in vivo and in vitro. calmodulin
      kinase II (CaMKII) is a proarrhythmic molecule known to drive SR Ca2+
      mishandling. RESULTS: The authors report for the first time that binge alcohol
      activates JNK2, which subsequently phosphorylates the CaMKII protein, enhancing
      CaMKII-driven SR Ca2+ mishandling. CaMKII inhibition eliminates binge alcohol
      evoked arrhythmic activities. CONCLUSIONS: Our studies demonstrate that binge
      alcohol exposure activates JNK2 in atria, which then drives CaMKII activation,
      prompting aberrant Ca2+ waves and, thus, enhanced susceptibility to atrial
      arrhythmia. Our results reveal a previously unrecognized form of alcohol-driven
      kinase-on-kinase proarrhythmic crosstalk. Atrial JNK2 function represents a
      potential novel therapeutic target to treat and/or prevent AF.

PMID- 29598869
TI  - Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?
AB  - Most guidelines for the management of patients with cardiovascular disease
      recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy,
      whereas angiotensin receptor blockers (ARBs) are merely considered an alternative
      for ACE inhibitor-intolerant patients. The aim of this review was to compare
      outcomes and adverse events between ACE inhibitors and ARBs in patients. In
      patients with hypertension and hypertension with compelling indications, we found
      no difference in efficacy between ARBs and ACE inhibitors with regard to the
      surrogate endpoint of blood pressure and outcomes of all-cause mortality,
      cardiovascular mortality, myocardial infarction, heart failure, stroke, and end
      stage renal disease. However, ACE inhibitors remain associated with cough and a
      very low risk of angioedema and fatalities. Overall withdrawal rates because of
      adverse events are lower with ARBs than with ACE inhibitors. Given the equal
      outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in
      aggregate indicates that at present there is little, if any, reason to use ACE
      inhibitors for the treatment of hypertension or its compelling indications.

PMID- 29598870
TI  - Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist
      Systems.
AB  - Recent progress and evolution in device engineering, surgical implantation
      practices, and periprocedural management have advanced the promise of durable
      support with left ventricular assist systems (LVAS) in patients with stage D
      heart failure. With greater uptake of LVAS globally, a growing population of LVAS
      recipients have pre-existing cardiac implantable electronic devices (CIEDs).
      Strategies for optimal clinical management of CIEDs in patients with durable LVAS
      are evolving, and clinicians will increasingly face complex decisions regarding
      implantation, programming, deactivation, and removal of CIEDs. Traditional
      decision-making pathways for CIEDs may not apply to LVAS-supported patients, as
      few patients die of arrhythmic causes and many arrhythmias may be well tolerated.
      Given limited data, treatment decisions must be individualized and made
      collaboratively among electrophysiologists, advanced heart failure specialists,
      and patients and their caregivers. Large, prospective, well-conducted studies are
      needed to better understand the contemporary utility of CIEDs in patients with
      newer-generation LVAS.

PMID- 29598871
TI  - Reply: When in Rome (Kentucky), Do (Not) What the Romans Do.

PMID- 29598872
TI  - When in Rome (Kentucky), Do (Not) What the Romans Do.

PMID- 29598873
TI  - Optogenetic Neuromodulation of Stellate Ganglia for Patients With Ventricular
      Arrhythmias, Atrial Fibrillation, Angina, and Takotsubo?

PMID- 29598875
TI  - Correction.

PMID- 29598874
TI  - Reply: Optogenetic Neuromodulation of Stellate Ganglia for Patients With
      Ventricular Arrhythmias, Atrial Fibrillation, Angina, and Takotsubo?

PMID- 29598876
TI  - Correction.

PMID- 29598877
TI  - Dash Cam videos on YouTubeTM offer insights into factors related to moose-vehicle
      collisions.
AB  - To gain a better understanding of the dynamics of moose-vehicle collisions, we
      analyzed 96 videos of moose-vehicle interactions recorded by vehicle dash-mounted
      cameras (Dash Cams) that had been posted to the video-sharing website YouTubeTM.
      Our objective was to determine the effects of road conditions, season and
      weather, moose behavior, and driver response to actual collisions compared to
      near misses when the collision was avoided. We identified 11 variables that were
      consistently observable in each video and that we hypothesized would help to
      explain a collision or near miss. The most parsimonious logistic regression model
      contained variables for number of moose, sight time, vehicle slows, and vehicle
      swerves (AICcw = 0.529). This model had good predictive accuracy (AUC = 0.860, SE
      = 0.041). The only statistically significant variable from this model that
      explained the difference between moose-vehicle collisions and near misses was
      'Vehicle slows'. Our results provide no evidence that road surface conditions
      (dry, wet, ice or snow), roadside habitat type (forested or cleared), the extent
      to which roadside vegetation was cleared, natural light conditions (overcast,
      clear, twilight, dark), season (winter, spring and summer, fall), the presence of
      oncoming traffic, or the direction from which the moose entered the roadway had
      any influence on whether a motorist collided with a moose. Dash Cam videos posted
      to YouTubeTM provide a unique source of data for road safety planners trying to
      understand what happens in the moments just before a moose-vehicle collision and
      how those factors may differ from moose-vehicle encounters that do not result in
      a collision.

PMID- 29598878
TI  - Design Engineering in Surgery. How to Design, Test and Market Surgical Devices
      Made With 3D Printing?
AB  - Industry 4.0 offers new development opportunities for surgeons. Computer-aided
      design and 3D printing allow for the creation of prototypes and functional end
      products. Until now, it was difficult for new devices to get to the manufacturing
      phase. Nowadays, the main limitations are our creativity, available spaces to
      test our creations and obtaining financing.

PMID- 29598879
TI  - Optimizing Lung Collapse With a Bronchial Blocker: It's Not What You Use, but How
      You Use It.

PMID- 29598880
TI  - Unusual Prebypass Echocardiographic Findings Before Bicuspid Aortic Valve
      Surgery.

PMID- 29598881
TI  - [Prevent bacteria from communicating: Divide to cure].
AB  - Quorum Sensing (QS) is a communication system used by numerous bacteria to
      synchronize their behavior according to the cell density. In this way, bacteria
      secrete and sense small mediating molecules, called autoinducers (AI), which
      concentration increases in the environment proportionally to bacterial cell
      number. QS induces major physiological and phenotypic changes such as virulence
      induction and biofilm formation. Biofilm represents a physical barrier which
      shelters bacteria poorly sensitive to antimicrobial treatments and favors the
      apparition of resistance mechanisms. Disturbing QS is referred to as quorum
      quenching (QQ). This strategy is used by microorganisms themselves to prevent the
      development of specific group behaviors. Two strategies are mainly employed: the
      use of quorum sensing inhibitors (QSI) and of quorum quenching enzymes (QQE) that
      degrades AI. Many studies have been dedicated to identifying QSI (natural or
      synthetic) as well as QQE and demonstrating their anti-virulence and anti-biofilm
      effects on numerous bacterial species. Synergistic effects between QQ and
      traditional treatments such as antibiotherapy or with reemerging phage therapy
      have been put forward. The efficiency of numerous QSI and QQE was thereby
      demonstrated either with in vitro or in vivo animal models leading to the
      development of medical devices containing QSI and QQE to improve already existing
      treatments.

PMID- 29598882
TI  - Aging resistance, mechanical properties and translucency of different yttria
      stabilized zirconia ceramics for monolithic dental crown applications.
AB  - OBJECTIVES: The dental market moves towards high-translucency monolithic zirconia
      dental crowns, which are usually placed either with - or without - a thin glaze
      layer. The microstructural features and the mechanical performances of these
      materials are still controversial, as well as their susceptibility to aging. This
      paper aims at studying these aspects in the current generation of zirconia dental
      crowns showing different degrees of translucency. METHODS: Four different
      commercial zirconia materials were investigated, including one standard 'full
      strength' 3Y-TZP and three grades with improved translucency. The microstructural
      features (phase composition and assemblage, grain size) were carefully studied,
      as well as mechanical properties (biaxial bending strength and indentation
      toughness), translucency and aging behavior (in autoclave at 134 degrees C).
      Aging was conducted on crowns with and without glaze to better represent clinical
      uses. RESULTS: Important differences are found in terms of microstructures among
      the materials in terms of cubic phase content and yttria in the tetragonal phase,
      leading to different optical, mechanical and aging resistance properties. We show
      that higher cubic phase content leads to better translucency and stability in
      water steam, but at the expense of strength and toughness. A compromise is always
      inevitable between translucency and aging resistance on one side and mechanical
      properties on the other side. SIGNIFICANCE: 

PMID- 29598883
TI  - Effect of vitamin D and omega-3 on nocturnal enuresis of 7-15-year-old children.
AB  - INTRODUCTION: Nocturnal enuresis is known to be a common urinary bladder
      complication in children. Recent studies have associated vitamin D and omega-3
      insufficiency with nocturnal enuresis. AIM: This was a 2-month randomized,
      placebo-controlled, double-blind trial to measure the effects of vitamin D, omega
      3 supplements, and their combination on nocturnal enuresis among 7-15-year-old
      children. MATERIALS AND METHODS: Participants (180 children with nocturnal
      enuresis) were selected from children referred to the Pediatric ward of Imam Reza
      Clinic in Shiraz, Iran. Demographic information and anthropometric measures were
      taken. Fasting blood and urine samples were also collected, and serum vitamin D
      and urine prostaglandin E2 were measured before and after intervention. Enuretic
      children were randomly assigned to four groups: Group A, vitamin D (1000 IU/day);
      Group B, omega-3 (1000 mg/day); Group C, both omega-3 (1000 mg/day) and vitamin D
      (1000 IU/day); and Group D, placebo. RESULTS: The results suggested that the
      study groups were not significantly different regarding demographic and
      anthropometric measures at baseline. Comparison of different groups revealed that
      44.4% of participants in Group A, 28.2% of Group B and 45% of Group C were cured
      from enuresis (P = 0.03). Serum 25(OH) D was significantly increased in Group A,
      but urine prostaglandin E2 was not significantly decreased in response to
      supplementation. Although supplementation with both Group A and Group B were
      found to be effective, the combined intervention did not increase the effect of
      each intervention solely. CONCLUSIONS: The results showed that supplementation
      with vitamin D and omega-3 could reduce the number of wet nights among 7-15-year
      old children with nocturnal enuresis.

PMID- 29598885
TI  - Equity in access to care in the era of health system reforms in Turkey.
AB  - OBJECTIVE: To evaluate access to healthcare from an equity perspective on the way
      toward Universal Health Coverage in Turkey. METHODS: The country representative
      data from 2006 to 2013 Turkey Income and Living Conditions Surveys were analyzed.
      Private household residents aged fifteen and older were asked for self-reported
      unmet need for medical care in the past twelve months. The dependent variable had
      three categories: no unmet need, unmet need due to cost, and unmet need due to
      availability (waiting list and distance problems). Predictors of unmet need were
      assessed by a multinomial logistic regression analysis. FINDINGS: The prevalence
      of unmet need declined between 2006 and 2013. While educational inequalities in
      declared unmet need also decreased, the income gradient becomes more important.
      In 2013, controlling for other factors, the propensity to report unmet need was
      10 times higher for those in the poorest-income quintile compared to the richest
      (versus 7 times in 2006). CONCLUSION: Overall access to healthcare has gradually
      improved in Turkey in the health reform process, but 9% of people still declared
      unmet need due to cost in 2013, after the implementation of Universal Health
      Insurance. This was nearly four times the EU average. Unfavourable economic and
      labour market conditions can be challenges for effective universal health
      coverage.

PMID- 29598884
TI  - Outcome of clinical management in relatives of sudden cardiac death victims.
AB  - BACKGROUND: International guidelines recommend clinical assessment of the
      surviving first-degree relatives of sudden cardiac death (SCD) victims to
      identify a probable cause of death and protect surviving relatives. Only few
      studies have reported the outcome of clinical management and follow-up of
      relatives to SCD victims. METHODS: We performed a retrospective cohort study of
      the clinical and genetic assessment of surviving relatives of SCD victims
      referred to the Clinic of Inherited Cardiac Diseases at Aarhus University
      Hospital, Denmark, between 1995 and 2016. We studied clinical and autopsy
      findings on all cases of SCD among children and adults. Relatives were followed
      for adverse cardiovascular events including cardiac hospitalization, new-onset
      heart failure, coronary heart disease, malignant syncope or documented malignant
      ventricular arrhythmias, and death. RESULTS: We included 292 relatives of 56 SCD
      victims. During a median (interquartile range) follow-up of 3.3 (1.6-4.7) years
      twelve relatives experienced an adverse cardiovascular event of which only five
      were related to the inherited cardiac disease in the family. One developed
      dilated cardiomyopathy and one tachycardia induced heart failure, five suffered
      from ventricular tachycardia or a malignant syncope and received a secondary
      prophylactic Implantable Cardioverter Defibrillator, three had a coronary heart
      disease event and two died from old age. CONCLUSION: Relatives of SCD victims
      have a low rate of adverse cardiac events when guideline-based assessment and
      care is applied.

PMID- 29598886
TI  - Mapping existing hip and knee replacement registries in Europe.
AB  - The general shortage of evidence regarding benefits and harms of medical devices
      has been highlighted following the serious safety concerns with metal-on-metal
      hip replacements and silicone breast implants and was again pointed out in a
      recent survey of European Health Technology Assessment institutions. In this
      context the new European medical device regulation will enforce post-marketing
      surveillance of existing and new implants. The usefulness of registry data as a
      source of information for medical device real-world clinical performance and
      safety has been demonstrated. However, these data might be under-used by
      researchers and policy makers. One reason for this is the insufficient awareness
      of their existence. The aim of this review is to provide information to relevant
      stakeholders on the extent and breadth of the data currently collected in
      European joint replacement registries. We identified 24 registries, most of them
      of national coverage. Total numbers of primary total hip and knee replacements
      included were over 3.1 and 2.5 million records, respectively. The current focus
      of these registries is on whole-lifespan implant surveillance via revision rate
      monitoring, quality assessment of surgical and perioperative care, and hospital
      performance assessment. More recently, national and international comparison and
      benchmarking have increasingly become part of their endeavors.

PMID- 29598888
TI  - Down syndrome people capable of learning and performing foreign body airway
      obstruction treatment algorithm.

PMID- 29598887
TI  - Expression of programmed cell death 1/programmed cell death ligand 1 in the tumor
      microenvironments of primary gastrointestinal diffuse large B cell lymphomas.
AB  - BACKGROUND: Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most
      common gastrointestinal lymphoma. However, there has not been a comprehensive
      investigation into the expression patterns of programmed cell death 1 (PD-1) and
      programmed cell death ligand 1(PD-L1) in GI DLBCL tissues. METHODS: PD-1 protein
      expression in tumor-infiltrating lymphocytes (TILs) was evaluated by
      immunohistochemical staining, and expression of PD-L1 was evaluated by using PD
      L1/PAX5 immunohistochemical double staining in 92 GI DLBCL specimens. RESULTS:
      The prevalence of positive PD-L1 expression (PD-L1 + ) in GI DLBCL cells and
      positive PD-L1 expression in non-cancer cells of the GI DLBCL microenvironment
      (microenvironmental PD-L1, mPD-L1) were 11.96% (11 of 92) and 41.98% (34 of 81),
      respectively. PD-L1 expression in GI DLBCL was significantly associated with
      involvement of extranodal sites >= 2 (P = 0.034) and mPD-L1 expression was
      significantly associated with ECOG performance status (score >= 2) (P = 0.041).
      PD-L1 expression and mPD-L1 expression had no prognostic significance (P > 0.05)
      on disease outcome. PD-1+ TILs were significantly lower in patients with
      extranodal site involvement (P = 0.011) and the quantity of PD-1 + TILs
      correlated positively with the level of PDL1 expression in non malignant
      microenvironment cells (P = 0.001). Patients with high levels of PD-1+ TILs had
      better prognosis (P = 0.0005). CONCLUSIONS: The expression patterns of PD-L1 in
      patients with GI DLBCL are different from patients with common DLBCL.
      Immunotherapies that target the PD-1/PD-L1 pathway may have therapeutic potential
      in GI DLBCL.

PMID- 29598889
TI  - Severe malaria presenting to the ED: A collaborative approach utilizing exchange
      transfusion and artesunate.
AB  - We describe the case of a previously healthy 33year-old male pilot recently
      arrived to the United States from Africa. The patient presented to our ED febrile
      and disoriented, with projectile coffee-ground emesis. He was later found to have
      severe malaria and cerebral parasitemia. Due to the severity of his illness, the
      patient received the anti-malarial medication Artesunate as well as several
      exchange transfusions. Within 48h his parasitic load was reduced from 42% to
      0.4%. The following is an account of a collaborative effort that spans the
      specialties of emergency medicine, infectious disease, and critical care
      medicine.

PMID- 29598890
TI  - Closed-loop intracranial stimulation alters movement timing in humans.
AB  - BACKGROUND: A prime objective driving the recent development of human neural
      prosthetics is to stimulate neural circuits in a manner time-locked to ongoing
      brain activity. The human supplementary motor area (SMA) is a particularly useful
      target for this objective because it displays characteristic neural activity just
      prior to voluntary movement. OBJECTIVE: Here, we tested a method that detected
      activity in the human SMA related to impending movement and then delivered
      cortical stimulation with intracranial electrodes to influence the timing of
      movement. METHODS: We conducted experiments in nine patients with electrodes
      implanted for epilepsy localization: five patients with SMA electrodes and four
      control patients with electrodes outside the SMA. In the first experiment,
      electrocorticographic (ECoG) recordings were used to localize the electrode of
      interest during a task involving bimanual finger movements. In the second
      experiment, a real-time sense-and-stimulate (SAS) system was implemented that
      delivered an electrical stimulus when pre-movement gamma power exceeded a
      threshold. RESULTS: Stimulation based on real-time detection of this supra
      threshold activity resulted in significant slowing of motor behavior in all of
      the cases where stimulation was carried out in the SMA patients but in none of
      the patients where stimulation was performed at the control site. CONCLUSIONS:
      The neurophysiological correlates of impending movement can be used to trigger a
      closed loop stimulation device and influence ongoing motor behavior in a manner
      imperceptible to the subject. This is the first report of a human closed loop
      system designed to alter movement using direct cortical recordings and direct
      stimulation.

PMID- 29598891
TI  - Outcomes of dialysis patients with critical limb ischemia after revascularization
      compared with patients with normal renal function.
AB  - OBJECTIVE: An analysis was conducted of intermediate outcomes and possible
      influencing factors in patients with end-stage renal disease (ESRD) and critical
      limb ischemia after lower limb revascularization compared with patients with
      regular renal function (non-ESRD). METHODS: Data collection was performed by
      inquiry of the German multicenter registry of First-Line Treatments in Patients
      with Critical Limb Ischemia (CRITISCH); 102 ESRD patients and 674 non-ESRD
      patients were included. Four different therapy modalities were analysed: bypass
      surgery, endovascular therapy (EVT), femoral artery endarterectomy, and no
      vascular intervention (conservative treatment or primary major amputation).
      Predefined end points were amputation-free survival (AFS), death, major
      amputation, and reintervention. Cox regression models were built to analyze
      independent risk factors for outcome parameters. RESULTS: ESRD patients showed
      inferior results at 2 years in the rate of AFS (ESRD, 35.4%; non-ESRD, 67.2%; P <
      .001). Similarly, death rate (ESRD, 55.0%; non-ESRD, 20.7%; P < .001) and major
      amputation rate (ESRD, 24.5%; non-ESRD, 15.8%; P = .029) were significantly
      elevated for ESRD patients. The choice of therapeutic approach in ESRD did not
      influence the incidence of the investigated end points (death or major
      amputation: EVT, 56.9% vs bypass, 76.9% [P = .225]; death: EVT, 46.2% vs bypass,
      61.5% [P = .372]; amputation: EVT, 15.4% vs bypass, 15.4% [P = 1.000];
      reintervention: EVT, 32.3% vs bypass, 15.4% [P = .324]). Cox regression analysis
      indicated that dialysis patients carry a twofold increased hazard of death or
      major amputation (hazard ratio, 2.27; 95% confidence interval, 1.67-3.10; P <
      .001), and open surgical treatment (all patients combined) was associated with
      reduced risk of death compared with EVT (hazard ratio, 0.58; 95% confidence
      interval, 0.37-0.91; P = .017). Comorbidities were not found to have a noticeable
      impact on AFS, survival, reintervention, or major amputation. CONCLUSIONS: Two
      year AFS, overall survival, and freedom from major amputation were decreased in
      ESRD patients compared with non-ESRD patients with critical limb ischemia.
      Cardiovascular comorbidities were without significant impact on outcome
      parameters, whereas choice of treatment modality within the ESRD group did not
      influence AFS. Decision-making in ESRD as to choice of therapeutic approach in
      dialysis patients should notably account for the individual's lesion
      characteristics and vascular disease; surgical revascularization and EVT may be
      used as complementary options.

PMID- 29598892
TI  - Editorial Comment.

PMID- 29598893
TI  - Editorial Comment.

PMID- 29598894
TI  - Author Reply.

PMID- 29598895
TI  - Triple innervation for re-animation of recent facial paralysis.
AB  - Recent facial palsies are those in which fibrillations of the mimetic musculature
      remain detectable by electromyography (EMG). Such fibrillations generally cease
      18-24 months after palsy onset. During this period, facial re-animation surgery
      seeks to supply new neural inputs to the facial nerve. Neural usable sources were
      divided into qualitative (contralateral facial nerve) and quantitative
      (hypoglossus and masseteric nerve), depending on the type of stimulus provided.
      To further improve the extent and quality of facial re-animation, we here
      describe a new surgical technique featuring triple neural inputs: the use of the
      masseteric nerve and 30% of the hypoglossus nerve fibres as quantitative sources
      was associated with the contralateral facial nerve (incorporated via two cross
      face nerve grafts) as a qualitative source in order to restore facial movements
      in 24 consecutive patients. The use of two quantitative motor nerve sources
      together with a qualitative neural source appears to improve re-animation after
      facial paralysis, despite earlier doubts as to whether patients could use
      different nerves to produce facial movements. In fact, movement was much
      improved. Smiling according to emotions and blinking seem to be better assured if
      cross-face nerve grafting is performed in two steps rather than one.

PMID- 29598896
TI  - Effects of hammock positioning in behavioral status, vital signs, and pain in
      preterms: a case series study.
AB  - BACKGROUND: The hammock positioning within the incubators simulates the
      intrauterine environment, however, there is little evidence of its benefits and
      possible risks. OBJECTIVES: The aim of this study was to assess the effects of
      hammock positioning on behavioral status, vital signs, and pain in very low birth
      weight preterm newborns. METHODS: This is a quasi-experimental/case series study
      in which premature infants (<1500g) were positioned in supine for one hour in a
      hammock. The preterm newborns were assessed 10min before, during (2, 20, 40, and
      60min), and 10min after hammock positioning with the Brazelton Neonatal
      Behavioral Assessment Scale, vital signs and pain by the Neonatal Facial Coding
      System. RESULTS: 28 preterm infants between 28 and 36 weeks of gestational age
      were evaluated. Regarding the behavioral state, the preterm newborns
      progressively evolved to light or deep sleep during hammock positioning. There
      was a statistically significant reduction of the heart and respiratory rate from
      2 to 60th minute in a hammock, which was maintained after the positioning. The
      oxygen saturation remained within normal values. No changes in pain scores were
      observed. CONCLUSION: The hammock positioning can be considered a safe method of
      positioning that can be used to reduce the stress levels in very low birth weight
      preterm newborns. We did not observe worsening in either pain or vital signs.

PMID- 29598897
TI  - Feasibility and safety of treating non-unions in tibia, femur and humerus with
      autologous, expanded, bone marrow-derived mesenchymal stromal cells associated
      with biphasic calcium phosphate biomaterials in a multicentric, non-comparative
      trial.
AB  - BACKGROUND: ORTHO-1 is a European, multicentric, first in human clinical trial to
      prove safety and feasibility after surgical implantation of commercially
      available biphasic calcium phosphate bioceramic granules associated during
      surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM
      hMSC) under good manufacturing practices, in patients with long bone
      pseudarthrosis. METHODS: Twenty-eight patients with femur, tibia or humerus
      diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically
      treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL
      associated with 5-10 cc of bioceramic granules. Patients were followed up during
      one year. The investigational advanced therapy medicinal product (ATMP) was
      expanded under the same protocol in all four countries, and approved by each
      National Competent Authority. FINDINGS: With safety as primary end-point, no
      severe adverse event was reported as related to the BM-hMSC. With feasibility as
      secondary end-point, the participating production centres manufactured the BM
      hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to
      the non-unions, and 26/28 treated patients were found radiologically healed at
      one year (3 out of 4 cortices with bone bridging). INTERPRETATION: Safety and
      feasibility were clinically proven for surgical implantation of expanded
      autologous BM-hMSC with bioceramic. FUNDING: EU-FP7-HEALTH-2009, REBORNE Project
      (GA: 241876).

PMID- 29598898
TI  - Notes on maternal behaviour in soft ticks: Specifically observed in Argas (Argas)
      striatus Bedford, 1932 and Argas (Secretargas) transgariepinus White, 1846.
AB  - Maternal behaviour (carrying of larvae on the opisthosoma) in ticks has thus far
      only been observed in Antricola (Parantricola) marginatus and was considered a
      unique derived adaptation of this genus. The authors extend this observation to
      two additional argasid species, namely Argas (Argas) striatus and Argas
      (Secretargas) transgariepinus. In addition, brooding behaviour over eggs were
      observed with A. (S.) transgariepinus. Maternal behaviour may be an evolutionary
      adaptation to ecological challenges in habitats unsuited for larval survival and
      may be related to the presence of pulvilli in larvae. This adaptation might have
      been present in the ancestral tick lineage since pulvilli occur in all tick
      families, and may have been derived from a more ancient adaptation in
      chelicerates where maternal behaviour was common. Female A. (S.) transgariepinus
      also possess a unique area on their ventral abdomen that is absent in males and
      may be a unique adaptation for maternal behaviour in this species. Phylogenetic
      analysis of the 16S rRNA genes for both species indicate that they are unique
      lineages that group basal to other members of the Argas genus, supporting the
      possibility that they harbour ancestral traits for this group.

PMID- 29598899
TI  - Anosmia and nasal obstruction.

PMID- 29598900
TI  - Small-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1
      interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance.
AB  - REV1 protein is a mutagenic DNA damage tolerance (DDT) mediator and encodes two
      ubiquitin-binding motifs (i.e., UBM1 and UBM2) that are essential for the DDT
      function. REV1 interacts with K164-monoubiquitinated PCNA (UbPCNA) in cells upon
      DNA-damaging stress. By using AlphaScreen assays to detect inhibition of REV1 and
      UbPCNA protein interactions along with an NMR-based strategy, we identified small
      molecule compounds that inhibit the REV1/UbPCNA interaction and that directly
      bind to REV1 UBM2. In cells, one of the compound prevented recruitment of REV1 to
      PCNA foci on chromatin upon cisplatin treatment, delayed removal of UV-induced
      cyclopyrimidine dimers from nuclei, prevented UV-induced mutation of HPRT gene,
      and diminished clonogenic survival of cells that were challenged by
      cyclophosphamide or cisplatin. This study demonstrates the potential utility of a
      small-molecule REV1 UBM2 inhibitor for preventing DDT.

PMID- 29598901
TI  - Macrocyclic alpha helical peptide therapeutic modality: A perspective of
      learnings and challenges.
AB  - Macrocyclic alpha-helical peptides have emerged as a compelling new therapeutic
      modality to tackle targets confined to the intracellular compartment. Within the
      scope of hydrocarbon-stapling there has been significant progress to date,
      including the first stapled alpha-helical peptide to enter into clinical trials.
      The principal design concept of stapled alpha-helical peptides is to mimic a
      cognate (protein) ligand relative to binding its target via an alpha-helical
      interface. However, it was the proclivity of such stapled alpha-helical peptides
      to exhibit cell permeability and proteolytic stability that underscored their
      promise as unique macrocyclic peptide drugs for intracellular targets. This
      perspective highlights key learnings as well as challenges in basic research with
      respect to structure-based design, innovative chemistry, cell permeability and
      proteolytic stability that are essential to fulfill the promise of stapled alpha
      helical peptide drug development.

PMID- 29598902
TI  - Retraction notice to "CD133+/CD44+/Oct4+/Nestin+ stem-like cells isolated from
      Panc-1 cell line may contribute to multi-resistance and metastasis of pancreatic
      cancer" [Acta Histochemica 115 (2013) 349-356].

PMID- 29598903
TI  - Regulatory perspective on in vitro potency assays for human T cells used in anti
      tumor immunotherapy.
AB  - The adaptive immune system is known to play an important role in anti-neoplastic
      responses via induction of several effector pathways, resulting in tumor cell
      death. Because of their ability to specifically recognize and kill tumor cells,
      the potential use of autologous tumor-derived and genetically engineered T cells
      as adoptive immunotherapy for cancer is currently being explored. Because of the
      variety of potential T cell-based medicinal products at the level of starting
      material and manufacturing process, product-specific functionality assays are
      needed to ensure quality for individual products. In this review, we provide an
      overview of in vitro potency assays suggested for characterization and release of
      different T cell-based anti-tumor products. We discuss functional assays, as
      presented in scientific advices and literature, highlighting specific advantages
      and limitations of the various assays. Because the anticipated in vivo mechanism
      of action for anti-tumor T cells involves tumor recognition and cell death, in
      vitro potency assays based on the cytotoxic potential of antigen-specific T cells
      are most evident. However, assays based on other T cell properties may be
      appropriate as surrogates for cytotoxicity. For all proposed assays, biological
      relevance of the tests and correlation of the read-outs with in vivo
      functionality need to be substantiated with sufficient product-specific (non
      )clinical data. Moreover, further unraveling the complex interaction of immune
      cells with and within the tumor environment is expected to lead to further
      improvement of the T cell-based products. Consequently, increased knowledge will
      allow further optimized guidance for potency assay development.

PMID- 29598904
TI  - Lipopolysaccharide Induces Subacute Cerebral Microhemorrhages with Involvement of
      Nitric Oxide Synthase in Rats.
AB  - BACKGROUND: Cerebral microhemorrhage (CMH) is a neuropathological term that could
      be easily found in cerebral amyloid angiopathy, intracerebral hemorrhages, etc.
      CMHs could be detected clearly in vivo by magnetic resonance imaging (MRI)
      susceptibility-weighted imaging or MRI T2* scan. This terminology is now accepted
      in the area of neuroimaging. CMHs are quite common in elderly patients and are
      associated with several other neuropsychiatric disorders. The causes of CMHs are
      complicated, and neuroinflammation is considered as one of the well-accepted
      mechanical factors. This study investigated whether lipopolysaccharide (LPS)
      induced CMHs occur through the regulation of nitric oxide synthase (NOS) isoforms
      and reveals the exact underlying mechanism of LPS-induced CMHs. METHODS: Our work
      successfully developed a subacute model of CMHs in rats. LPS was
      intraperitoneally injected into rats at 0, 6, and 24 hours, which induced typical
      CMH features 7 days after the injection. These could be detected on the brain
      surface or parenchyma by hematoxylin and eosin staining and MRI. RESULTS: LPS
      treated rats showed significant activation of astrocytes and microglia, as well
      as loss of pericytes and disruption of blood-brain barrier. Meanwhile, both
      astrocytes and microglia were positively correlated with CMH numbers.
      Furthermore, the expressions of NOS isoforms were also examined, and the levels
      of neuronal NOS and endothelial NOS were found to be elevated. CONCLUSIONS: These
      results implied that the NOS isoforms might be involved in the subacute model of
      CMHs in rats induced by LPS.

PMID- 29598905
TI  - The Accuracy of Serum Matrix Metalloproteinase-9 for Predicting Hemorrhagic
      Transformation After Acute Ischemic Stroke: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Hemorrhagic transformation is a serious complication of acute
      ischemic stroke, which may cause detrimental outcomes and the delayed use of
      anticoagulation therapy. Early predicting and identifying the patients at high
      risk of hemorrhagic transformation before clinical deterioration occurrence
      become a research priority. OBJECTIVE: To study the value of plasma matrix
      metalloproteinase-9 predicting hemorrhagic transformation after ischemic stroke.
      METHODS: We searched PubMed, Ovid, Cochrane Library, and other 2 Chinese
      databases to identify literatures published up to September 2017 and performed
      meta-analysis by STATA (version 12.0, StataCorp LP, College Station, TX).
      RESULTS: Twelve studies incorporating 1492 participants were included and 7
      studies were included in the quantitative statistical analysis. The pooled
      sensitivity was 85% (95% confidence interval [CI]: 75%, 91%) and the pooled
      specificity was 79% (95% CI: 67%, 87%). The area under the receiver operating
      characteristic curve was .89 (95% CI .86, .91). Significant heterogeneity for all
      estimates value existed (all the P value < .05 and I2 > 50%). There is no
      threshold effect with P value greater than .05 of the correlation coefficient.
      Meta-regression and subgroup analysis showed cut-off value and hemorrhagic
      subtype contributed to heterogeneity. Deeks' funnel plot indicated no significant
      publication bias for 7 quantitative analysis studies. CONCLUSIONS: Matrix
      metalloproteinase-9 has high predictive value for hemorrhagic transformation
      after acute ischemic stroke. It may be useful to test matrix metalloproteinase-9
      to exclude patients at low risk of hemorrhage for precise treatment in the future
      clinical work.

PMID- 29598906
TI  - Posterior Meningeal Artery Origin Patterns among 300 Cases and Their Clinical
      Importance.
AB  - BACKGROUND AND PURPOSE: The posterior meningeal artery (PMA) is known as a dura
      mater-nourishing vessel. We encountered a patient with Wallenberg syndrome during
      transarterial embolization of the PMA associated with the dural arteriovenous
      fistula (DAVF). METHODS: After development of Wallenberg syndrome in the patient,
      we assessed origins of the PMA patterns in 300 cases and divided them into 3
      types. CASE PRESENTATION: A 63-year-old man was incidentally diagnosed as having
      transverse-sigmoid sinus DAVF with a cortical venous reflux. During the
      transarterial embolization, the patient complained of vertigo and numbness of the
      right extremities. Postoperatively, the patient exhibited Wallenberg syndrome.
      Diffusion-weighted magnetic resonance imaging showed a high-intensity area on the
      lateral side of the right medulla. CONCLUSIONS: While performing arterial
      embolization of the PMA that directly originates from the intracranial vertebral
      artery, the possibility of deficient brainstem nourishment must be considered.

PMID- 29598907
TI  - Upstream Stimulating Factor 1 (USF-1) Gene Polymorphisms and the Risk, Symptoms,
      and Outcome of Pediatric Ischemic Stroke.
AB  - BACKGROUND: Pediatric ischemic stroke is an important cause of morbidity and
      mortality. As previous studies of children after stroke showed, dyslipidemias
      were very common in Polish and other European populations. Thus, looking for
      genetic factors predisposing to pediatric stroke, its symptoms, and outcome, we
      have analyzed 2 polymorphisms of the upstream stimulating factor 1 (USF-1) gene.
      MATERIALS AND METHODS: The study group consisted of 82 children with stroke, 156
      parents, and 146 controls. We used 2 alternative methods: the case-control model
      and the analysis of families using the transmission disequilibrium test. The 2
      polymorphisms, rs2516839 and rs3737787, were genotyped using the TaqMan Pre
      Designed SNP Genotyping Assay. The Statistica 10.0 software was used in all
      statistical analyses. RESULTS: We did not observe any statistical differences in
      genotype and allele frequencies between patients and controls. There were also no
      significant differences in the transmission of alleles from the parents to the
      affected children. However, we have observed that the TT genotype of the
      rs2516839 polymorphism was more common in patients with epilepsy and dysarthria,
      whereas the TT genotype of the rs3737787 polymorphism was more frequent in the
      group of patients with a decrease in intellectual functioning. CONCLUSIONS: Our
      study did not show any associations between the 2 analyzed polymorphisms of the
      USF-1 gene and pediatric ischemic stroke. However, we have observed an influence
      of specific genotypes on the outcome of stroke, including epilepsy, dysarthria,
      and a decrease in intellectual functioning.

PMID- 29598908
TI  - Effects of Posturographic Platform Biofeedback Training on the Static and Dynamic
      Balance of Older Stroke Patients.
AB  - BACKGROUND: The aim of the experiment was to analyze the influence of
      posturographic platform biofeedback training on the static and dynamic balance of
      patients who experienced ischemic stroke. MATERIALS AND METHODS: The study
      included 20 patients treated at the Rehabilitation Center of the District
      Hospital in Bialogard, in the Ward of Neurological Rehabilitation with the Stroke
      Division. The age of the patients (10 in the experimental group and 10 in the
      control group) ranged between 60 and 72 years. The level of balance was
      determined with one-leg standing test and timed up & go test. The experimental
      group was subjected to the biofeedback training, practicing maintenance of body
      balance ("forced sway training") on posturographic platform for 15 consecutive
      days. RESULTS: The static balance on right leg and dynamic balance in group E
      improved to a markedly greater extent (P < .05) compared with conventionally
      rehabilitated group C. CONCLUSIONS: The effects of feedback mechanisms during
      training on a posturographic platform can be reflected by enhanced stimulation
      and further improvement of the control of different, more complicated performed
      motor tasks.

PMID- 29598909
TI  - Dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2-aminothiazoles
      and their cinnamamides as potent inhibitors of Mycobacterium tuberculosis.
AB  - Herein described the design, synthesis and antitubercular evaluation of novel
      series of dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2
      aminothiazoles and their cinnamamide analogs. One pot condensation of N-methyl
      carbazole, dibenzofuran and dibenzothiophene methyl ketones with thiourea in the
      presence of Iodine and CuO gave respective 2-aminothiazoles 4-6 in very good
      yields. Aminothiazoles were further coupled with substituted cinnamic acids using
      acid-amine coupling conditions to give desired cinnamamide analogs 8a-e, 9a-e and
      10a-e. All the newly synthesized compounds were fully characterized by their NMR
      and mass spectral analysis. In vitro screening of new derivatives against
      Mycobacterium tuberculosis H37Rv (Mtb) resulted 8c, 10d and 10e (MIC: 0.78 ug/mL)
      and 2-aminothiazoles 5 and 6 (MIC: 1.56 ug/mL) as potent compounds with lower
      cytotoxicity profile.

PMID- 29598910
TI  - Site-specific effect of polar functional group-modification in lipids of TLR2
      ligands for modulating the ligand immunostimulatory activity.
AB  - Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family,
      recognizes lipoproteins from bacteria and modulates the immune response by
      inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket
      that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have
      focused on the property of the hydrophobic TLR2 pocket. Based on the X-ray
      crystal structure of TLR2, small polar regions were found in the hydrophobic TLR2
      pocket. Interactions between the polar residues and ligands were explored here by
      designing and synthesizing a Pam2CSK4 derivative of the TLR2 ligands, containing
      an amide group within the lipid moiety. We evaluated the binding affinities and
      immunomodulatory activities of these ligands. Results suggested that the amide
      groups in the lipid chain interacted with the polar residues in the hydrophobic
      lipid-binding pocket of TLR2.

PMID- 29598911
TI  - One-pot, multicomponent synthesis of 2,3-disubstituted quinazolin-ones with
      potent and selective activity against Toxoplasma gondii.
AB  - The discovery of two quinazolinones with selective, single-digit micromolar
      activity (IC50 = 6-7 uM) against the tachyzoites of the apicomplexan parasite
      Toxoplasma gondii is reported. These potent and selective third generation
      derivatives contain a benzyloxybenzyl substituent at C2 and a bulky aliphatic
      moiety at N3. Here we show that these quinazolinones inhibit T. gondii tachyzoite
      replication in an established infection, but do not significantly affect host
      cell invasion by the tachyzoites.

PMID- 29598912
TI  - Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation
      and targeting clinically resistant Staphylococcus aureus DNA groove.
AB  - A novel series of purine benzimidazole hybrids were designed and synthesized for
      the first time with the aim to circumvent the increasing antibiotic resistance.
      Hexyl appended hybrid 3c gave potent activities against most of the tested
      bacteria and fungi especially against multidrug-resistant strains Staphylococcus
      aureus (MIC = 4 ug/mL). Structure-activity relationships revealed that the
      benzimidazole fragment at the 9-position of purine played an important role in
      exerting potentially antibacterial activity. Both cell toxicity and ROS
      generation assays indicated that the purine derivative 3c showed low cytotoxicity
      and could be used as a safe agent. Molecular modeling suggested that hybrid 3c
      could bind with the residues of Topo IA through hydrogen bonds and electrostatic
      interactions. Quantum chemical studies were also performed on the target compound
      3c to understand the structural features essential for activity. The active
      molecule 3c could effectively interact with S. aureus DNA to form 3c-DNA complex
      through groove binding mode, which might block DNA replication to display their
      powerful antimicrobial activity.

PMID- 29598913
TI  - Geriatric radiotherapy in a war-torn country: Experience from Iraq.
AB  - INTRODUCTION: Cancer prevalence and geriatric patients (GP) are increasing and
      about half of the patients with cancer will be offered radiotherapy (RT).
      Addressing GP and their RT needs is an important issue in order to understand
      this heterogeneous group of patients. MATERIALS AND METHODS: A descriptive cross
      sectional study, using a convenience sample from Sulaimani city's inhabitants,
      aged 70-year and more, who were treated with RT at the only city's RT center,
      Zhianawa Cancer Center (ZCC), in 2015. RESULTS: 153 patients' charts were
      reviewed. GP represented 20% of the patients referred to ZCC. Male: Female ratio
      was 3:1. One third presented with distant metastases, and 46% were treated with
      curative intent versus 54% with palliative intent. 94% completed the planned
      sessions of the curative RT vs 90% of the palliative RT. 23% of GP who were
      referred for RT didn't receive it. 9% got interruptions during RT course. 10% of
      GP living >40 km away from the treatment center refused treatment. Mean time
      interval between the date of referral and the date of starting treatment in the
      palliative setting was 19 days. Only 41% of patients with curative setting had
      regular follow-up. CONCLUSIONS: Being the 1st study in this regard in a war-torn
      nation, Iraq, our results demonstrated that GP is a sizable group of ZCC patients
      and that RT is a valuable modality in GP cancer treatment. "Age per se" is not a
      factor to avoid this modality when there is an indication to use it. Longer
      distance to reach the center was a challenge in some of our GP. Due to inadequate
      number of RT machines, GP have to wait long time before getting their RT, even
      for palliative purposes. Further studies in this field are warranted.

PMID- 29598914
TI  - Limitation of therapeutic effort in emergency departments: A shared decision.

PMID- 29598915
TI  - [Where is the left main coronary artery?]

PMID- 29598916
TI  - [Surgical management of abdominal tumours with cavoatrial extension without
      circulatory arrest].

PMID- 29598917
TI  - Risk factors for three-vessel coronary artery disease in patients of Northwest
      Mexico.
AB  - INTRODUCTION: Three-vessel coronary artery disease is an advanced manifestation
      of atherosclerosis, with high prevalence in Mexico. OBJECTIVE: The aim of this
      study was to describe coronary risk factors in a group of patients with three
      vessel coronary artery disease in Northwest Mexico. METHODS: A cross sectional
      study was conducted on a population with three-vessel coronary artery disease
      from May 2015 to February 2016. The disease was defined when >=70% stenosis was
      present in each major epicardial coronary artery. Anthropometric and biochemical
      parameters were measured in each patient. Ankle-Brachial Index was measured with
      vascular ultrasound, and Syntax score calculation with an on-line application.
      Statistical analysis for qualitative differences was performed using Pearson X2
      test, with p<0.05 being considered as significant. RESULTS: The study included
      100 patients, of whom 75 were male (mean age 63+/-9 years) and 25 female (mean
      age 69+/-9 years). The coronary risk factors observed were diabetes (58%),
      hypertension (86%), smoking (68%), dyslipidaemia (100%), metabolic syndrome
      (71%), and obesity/overweight (75%). Diabetes and metabolic syndrome prevalence
      was higher in women (p=0.03), but smoking was higher in men (76%, p=0.003). Ankle
      Brachial Index was abnormal in 58% of patients, the mean Syntax score was in
      36.9+/-11.5, and the prevalence of left main coronary heart disease was 36%.
      CONCLUSIONS: This group of patients with complex coronary lesions has a high
      prevalence of coronary risk factors, which could represent a worse prognosis.

PMID- 29598918
TI  - [An atypical presentation of third nerve palsy secondary to tuberculous
      meningoencephalitis in an immunocompetent patient].

PMID- 29598919
TI  - How much is enough?

PMID- 29598920
TI  - Amphioxus neurocircuits, enhanced arousal, and the origin of vertebrate
      consciousness.
AB  - Gene expression studies have recently identified the amphioxus homolog of a
      domain comprising the combined caudal diencephalon plus midbrain, regions
      implicated in locomotory control and some forms of primary consciousness in
      vertebrates. The results of EM-level reconstructions of the larval brain of
      amphioxus, reviewed here, highlight the importance of inputs to this region for
      light and physical contact, both of which impinge on the same synaptic zone. The
      neural circuitry provides a starting point for understanding the organization and
      evolution of locomotory control and arousal in vertebrates, and implies that one
      of the tasks of midbrain-based consciousness, as it first emerged in vertebrates,
      would have been to distinguish between light and physical contact, probably sharp
      pain in the latter case, by assigning different qualia to each. If so,
      investigating midbrain circuitry more fully could lead to a better understanding
      of the neural basis of some forms of sensory experience.

PMID- 29598921
TI  - What if you knew the prognosis of your patients with ALS?

PMID- 29598922
TI  - Diagnosis and assessment of neuropathic pain through questionnaires.
AB  - Neuropathic pain-pain caused by a lesion or disease of the somatosensory nervous
      system-is underdiagnosed and difficult to treat. However, development of easy-to
      use questionnaires based mainly on self-reports of symptoms has improved
      diagnosis and management. Two types of questionnaires (screening and assessment)
      have been validated, and rapidly translated and revalidated in several languages,
      probably because of their simplicity. Screening questionnaires help clinicians to
      identify neuropathic pain easily, particularly in patients with complex medical
      conditions (eg, spinal cord injury). Their use in large-scale epidemiological
      studies has provided estimates of the prevalence of neuropathic pain and
      identified risk factors for neuropathic pain in the general population and in
      disorders such as diabetes. Assessment questionnaires measure neuropathic
      symptoms and have been used to create phenotypic profiles of patients in various
      neuropathic conditions. These profiles can predict treatment outcomes, and thus
      enable a personalised therapeutic approach. The dissemination of these
      questionnaires in different countries should further improve diagnosis and
      management worldwide and advance knowledge on the mechanisms of neuropathic pain.

PMID- 29598924
TI  - Oncentra brachytherapy planning system.
AB  - In modern cancer management, treatment planning has progressed as a contemporary
      tool with all the advances in computing power in recent years. One of the
      advanced planning tools uses 3-dimensional (3D) data sets for accurate dose
      distributions in patient prescription. Among these planning processes,
      brachytherapy has been a very important part of a successful cancer management
      program, offering clinical benefits with specific or combined treatments with
      external beam therapy. In this chapter, we mainly discussed the Elekta Oncentra
      planning system, which is the main treatment planning tool for high-dose rate
      (HDR) modality in our facility and in many other facilities in the United States.
      HDR is a technically advanced form of brachytherapy; a high-intensity radiation
      source (3.6 mm in length) is delivered with step motor in submillimeter precision
      under computer guidance directly into the tumor areas while minimizing injury to
      surrounding normal healthy tissue. Oncentra planning is the key component to
      generate a deliverable brachytherapy procedure, which is executed on the
      microSelectron V3 remote afterloader treatment system. Creating a highly
      conformal plan can be a time-consuming task. The development of Oncentra software
      (version 4.5.3) offers a variety of useful tools that facilitate many of the
      clinical challenging tasks for planning, such as contouring and image
      reconstruction, as well as rapid planning calculations with dose and dose volume
      histogram analysis. Oncentra Brachy module creates workflow and optimizes the
      planning accuracy for wide varieties of clinical HDR treatments, such as skin,
      gynecologic (GYN), breast, prostate, and many other applications. The treatment
      file can also be transferred to the afterloader control station for speedy
      delivery. The design concept, calculation algorithms, and optimization modules
      presented some key characteristics to plan and treat the patients effectively and
      accurately. The dose distribution and accuracy of several clinical sample cases
      were discussed to illustrate the effectiveness and clinical efficacy. The
      American Association of Physicists in Medicine brachytherapy reports of TG-43 and
      TG-186 were also described and compared in evaluations of fundamental calculation
      methodologies.

PMID- 29598923
TI  - Prognosis for patients with amyotrophic lateral sclerosis: development and
      validation of a personalised prediction model.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive,
      fatal motor neuron disease with a variable natural history. There are no accurate
      models that predict the disease course and outcomes, which complicates risk
      assessment and counselling for individual patients, stratification of patients
      for trials, and timing of interventions. We therefore aimed to develop and
      validate a model for predicting a composite survival endpoint for individual
      patients with ALS. METHODS: We obtained data for patients from 14 specialised ALS
      centres (each one designated as a cohort) in Belgium, France, the Netherlands,
      Germany, Ireland, Italy, Portugal, Switzerland, and the UK. All patients were
      diagnosed in the centres after excluding other diagnoses and classified according
      to revised El Escorial criteria. We assessed 16 patient characteristics as
      potential predictors of a composite survival outcome (time between onset of
      symptoms and non-invasive ventilation for more than 23 h per day, tracheostomy,
      or death) and applied backward elimination with bootstrapping in the largest
      population-based dataset for predictor selection. Data were gathered on the day
      of diagnosis or as soon as possible thereafter. Predictors that were selected in
      more than 70% of the bootstrap resamples were used to develop a multivariable
      Royston-Parmar model for predicting the composite survival outcome in individual
      patients. We assessed the generalisability of the model by estimating
      heterogeneity of predictive accuracy across external populations (ie, populations
      not used to develop the model) using internal-external cross-validation, and
      quantified the discrimination using the concordance (c) statistic (area under the
      receiver operator characteristic curve) and calibration using a calibration
      slope. FINDINGS: Data were collected between Jan 1, 1992, and Sept 22, 2016 (the
      largest data-set included data from 1936 patients). The median follow-up time was
      97.5 months (IQR 52.9-168.5). Eight candidate predictors entered the prediction
      model: bulbar versus non-bulbar onset (univariable hazard ratio [HR] 1.71, 95% CI
      1.63-1.79), age at onset (1.03, 1.03-1.03), definite versus probable or possible
      ALS (1.47, 1.39-1.55), diagnostic delay (0.52, 0.51-0.53), forced vital capacity
      (HR 0.99, 0.99-0.99), progression rate (6.33, 5.92-6.76), frontotemporal dementia
      (1.34, 1.20-1.50), and presence of a C9orf72 repeat expansion (1.45, 1.31-1.61),
      all p<0.0001. The c statistic for external predictive accuracy of the model was
      0.78 (95% CI 0.77-0.80; 95% prediction interval [PI] 0.74-0.82) and the
      calibration slope was 1.01 (95% CI 0.95-1.07; 95% PI 0.83-1.18). The model was
      used to define five groups with distinct median predicted (SE) and observed (SE)
      times in months from symptom onset to the composite survival outcome: very short
      17.7 (0.20), 16.5 (0.23); short 25.3 (0.06), 25.2 (0.35); intermediate 32.2
      (0.09), 32.8 (0.46); long 43.7 (0.21), 44.6 (0.74); and very long 91.0 (1.84),
      85.6 (1.96). INTERPRETATION: We have developed an externally validated model to
      predict survival without tracheostomy and non-invasive ventilation for more than
      23 h per day in European patients with ALS. This model could be applied to
      individualised patient management, counselling, and future trial design, but to
      maximise the benefit and prevent harm it is intended to be used by medical
      doctors only. FUNDING: Netherlands ALS Foundation.

PMID- 29598925
TI  - Thermoplastic wrapped lead sheet to reduce cardiac device cumulative dose.
AB  - The objective of this project is to evaluate the percentage dose reduction in
      cardiac implantable electronic devices (CIEDs) using a thermoplastic wrapped lead
      sheet. The dose to CIED is evaluated in various situations with and without a
      lead shield. The efficiency of this type of shielding is supported by
      measurements made with a commercial plastic scintillation detector (PSD).
      Percentage depth dose (PDD) curve and lateral dose measurements (LDMs) were made
      with and without shielding for photon and electron beams. Photon LDMs were made
      at a depth of 0.5 cm. PSD measurements were compared with dose calculation from
      the treatment planning system (TPS). The benefit of shielding is greater at 23 MV
      than at 6 MV, with an average reduction of 71% and 59% of dose, respectively, for
      out-of-field distance range between 3 and 15 cm. Measurement of posterior beams
      shows there is no significant increase in skin dose due to backscatter from the
      lead sheet even when the field intercepts it. Large deviations between TPS
      calculation and measurements have been observed. The use of lead shielding with
      an anterior field is advised and provides an easy way to decrease the cumulative
      dose to CIEDs. Interception of shielding by an electron beam would increase
      significantly the cumulative dose to CIED for high energies or decrease the
      quality of the treatment. For a posterior out-of-field, shielding does not have a
      significant impact on CIED dose.

PMID- 29598926
TI  - Effects of heterogeneities in dose distributions under nonreference conditions:
      Monte Carlo simulation vs dose calculation algorithms.
AB  - The purpose of this study is to evaluate the performance of dose calculation
      algorithms used in radiotherapy treatment planning systems (TPSs) in comparison
      with Monte Carlo (MC) simulations in nonelectronic equilibrium conditions. MC
      simulations with PENELOPE package were performed for comparison of doses
      calculated by pencil beam convolution (PBC), analytical anisotropy algorithm
      (AAA), and Acuros XB TPS algorithms. Relative depth dose curves were calculated
      in heterogeneous water phantoms with layers of bone (1.8 g/cm3) and lung (0.3
      g/cm3) equivalent materials for radiation fields between 1 * 1 cm2 and 10 * 10
      cm2. Analysis of relative depth dose curves at the water-bone interface shows
      that PBC and AAA algorithms present the largest differences to MC calculations
      (uMC = 0.5%), with maximum differences of up to 4.3% of maximum dose. For the
      lung-equivalent material and 1 * 1 cm2 field, differences can be up to 24.3% for
      PBC, 11.5% for AAA, and 7.5% for Acuros. Results show that Acurus presents the
      best agreement with MC simulation data with equivalent accuracy for modeling
      radiotherapy dose deposition especially in regions where electronic equilibrium
      does not hold. For typical (nonsmall) fields used in radiotherapy, AAA and PBC
      can exhibit reasonable agreement with MC results even in regions of
      heterogeneities.

PMID- 29598928
TI  - Reply: Leaflet thrombosis following transcatheter aortic valve implantation.

PMID- 29598927
TI  - Epidemiology of hip fracture in nursing home residents with multiple sclerosis.
AB  - BACKGROUND: Hip fracture risk is high in young people with multiple sclerosis
      (MS), but has not been examined in an institutionalized aging population with MS.
      OBJECTIVE: We aimed to compare the hip fracture risk in nursing home (NH)
      residents with and without MS; and (2) examine risk factors for hip fracture in
      those with MS. METHODS: We conducted a retrospective cohort study using national
      NH clinical assessment and Medicare claims data. Participants included age-, sex-
      and race-matched NH residents with/without MS (2007-2008). Multivariable
      competing risk regression was used to compare 2-year hip fracture risk, and to
      examine risk factors. RESULTS: A total of 5692 NH residents with MS were matched
      to 28,460 without MS. Approximately 80% of residents with MS vs. 50% of those
      without MS required extensive assistance in walking at NH admission. The adjusted
      incidence rate of hip fracture was 7.1 and 18.6 per 1000 person-years in those
      with or without MS, respectively. Wandering and anxiolytic exposure were the main
      hip fracture risk factors in transfer independent residents with MS; while
      pneumonia and antidepressant use were the main factors in dependent residents
      with MS. CONCLUSIONS: In contrast to prior comparisons from non-NH populations,
      the incidence of hip fracture was lower in NH residents with MS as compared with
      matched controls. Residents with MS were much more functionally dependent, which
      likely explains these findings. Fracture prevention strategies should focus on
      fall prevention in independent residents; and possibly improvement of health
      status and facility quality of care in dependent residents.

PMID- 29598929
TI  - Relationship of the Duke jeopardy score combined with minimal lumen diameter as
      assessed by computed tomography angiography to the hemodynamic relevance of
      coronary artery stenosis.
AB  - OBJECTIVES: To study the diagnostic performance of the ratio between the Duke
      jeopardy score (DJS) and the minimal lumen diameter (MLD) (DJS/MLDCT ratio) as
      assessed by coronary computed tomographic angiography (CTA) for differentiating
      functionally significant from non-significant coronary artery stenoses, with
      reference to invasive fractional flow reserve (FFR). METHODS: Patients who
      underwent both coronary CTA and FFR measurement during invasive coronary
      angiography (ICA) within 2 weeks were retrospectively included in the study.
      Invasive FFR measurement was performed in patients with intermediate to severe
      coronary stenoseis. DJS/MLDCT ratio and anatomical parameters were recorded.
      Lesions with FFR <=0.80 were considered to be functionally significant. RESULTS:
      One hundred and sixty-one patients with 175 lesions were included into the
      analysis. Diameter stenosis in CT, area stenosis, plaque burden, lesion length
      (LL), ICA-based stenosis degree, DJS, LL/MLD4 ratio, DJS/MLA ratio as well as
      DJS/MLD ratio were all significantly different between hemodynamically
      significant and non-significant lesions (p<0.05 for all). ROC curve analysis
      determined the optimal cut-off value for DJS/MLDCT ratio to be 1.96 (area under
      curve = 0.863, 95 % confidence interval = 0.803-0.910), yielding a high
      diagnostic accuracy (86.9%, 152/175). CONCLUSIONS: In coronary artery stenoses
      detected by coronary CTA, the DJS/MLD ratio is able to predict hemodynamic
      relevance.

PMID- 29598930
TI  - Coronary computed tomography-derived fractional flow reserve assessment - Finally
      ready for clinical use?

PMID- 29598931
TI  - TARC expression in the circulation and cutaneous granulomas correlates with
      disease severity and indicates Th2-mediated progression in patients with
      sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a systemic disorder characterized by the accumulation
      of lymphocytes and monocyte/macrophage lineage cells that results in the
      formation of non-caseating granulomas. Thymus- and activation-regulated chemokine
      (TARC)/CCL17 is an important chemokine in the amplification of Th2 responses,
      which are achieved by recruiting CCR4-expressing CD4+ T lymphocytes. TARC
      concentrations are known to increase in the serum of sarcoidosis patients;
      however, its role in the assessment of severity and prognosis of sarcoidosis
      remains unknown. The objective of this study is to elucidate the role of TARC in
      sarcoidosis by investigating its expression in peripheral blood and at
      inflammatory sites. We also examined its relationship with clinical features.
      METHODS: Serum levels of TARC, soluble interleukin 2 receptor, angiotensin
      converting enzyme, and lysozyme were measured in 82 sarcoidosis patients. The Th1
      and Th2 balance in circulating CD4+ T cells was evaluated by flow cytometry. The
      immunohistochemical staining of TARC and CCR4 was performed in order to identify
      the source of TARC in affected skin tissues. RESULTS: TARC serum levels were
      elevated in 78% of patients and correlated with disease severity. The percentage
      of CCR4+ cells and the CCR4+/CXCR3+ cell ratios were significantly higher in
      sarcoidosis patients than in normal subjects (P = 0.002 and P = 0.015,
      respectively). Moreover, TARC was expressed by monocyte/macrophage lineage cells
      within granulomas. The abundancy as well as distribution of TARC staining
      correlated with its serum levels. CONCLUSIONS: The present results suggest that
      elevations in TARC drive an imbalanced Th2- weighted immune reaction and might
      facilitate prolonged inflammatory reactions in sarcoidosis.

PMID- 29598932
TI  - Glucagon like peptide-1 (GLP-1) likes Alzheimer's disease.
AB  - Glucagon-like peptide-1 (GLP-1) is a 30 amino acid long peptide hormone derived
      from the proglucagon gene and secreted in the distal small intestine when food
      enters the duodenum. GLP-1 is also produced in the central nervous system (CNS),
      predominantly in the brainstem, and subsequently transported to a large number of
      regions in the CNS. Neuronal cells in nucleus tractus solitarius (NTS) can
      synthesize GLP-1 and extends to hypothalamus, some thalamic and cortical areas. A
      G protein coupled receptor (GPCR) provides the majority of GLP-1 actions. GLP-1
      receptor activation triggers some in vivo signaling pathways. GLP-1 receptor
      agonists (GLP-1 RA) are used in the treatment diabetes and obesity. GLP-1
      stimulates insulin secretion, inhibits glucagon secretion, decreases food intake,
      reduces appetite, delays gastric emptying, provides weight reduction, and
      protects beta cells from apoptosis. Alzheimer's disease (AD) is the most
      prevalent form of dementia. It is characterized by cognitive insufficiencies and
      behavioral changes that impact memory and learning abilities, daily functioning
      and quality of life. Hyperinsulinemia and insulin resistance, which are known as
      pathophysiological features of the T2DM, have also been demonstrated to have
      significant impact on cognitive impairment. It is thought that GLP-1 affects
      neurological and cognitive functions, as well as its regulatory effect on glucose
      metabolism. The pathophysiological relationship between GLP-1 and AD is discussed
      in this review.

PMID- 29598934
TI  - "Time Is Muscle" in Acute Heart Failure: Critical Concept or Fake News?

PMID- 29598935
TI  - Indications for Cardiac Resynchronization Therapy: A Comparison of the Major
      International Guidelines.
AB  - OBJECTIVES: This study compares and contrasts the recommended indications for
      cardiac resynchronization therapy (CRT) according to the most recent guidelines
      from international cardiology societies. BACKGROUND: CRT has been shown to reduce
      morbidity and mortality in selected patients with systolic heart failure.
      Cardiology societies provide guidelines regarding the indications for CRT. As
      evidence evolves, it is challenging for the guideline committees to review the
      impact of newer evidence in a timely fashion. METHODS: Six of the most recent
      international guidelines providing recommendation concerning CRT implantation
      ranging from 2011 to 2017 were reviewed. These included guidelines from 2
      European, 1 North American, 1 Canadian, and 1 Australian/New Zealand societies
      and the National Institute for Health and Care Excellence guidelines, specific to
      the United Kingdom. RESULTS: Although international societies provide consistent
      recommendations for most CRT indications, differences are found in
      recommendations for several important patient populations. Specifically,
      divergent recommendations exist regarding QRS duration, bundle branch morphology,
      patients in atrial fibrillation, choice of device type (CRT pacemakers vs. CRT
      defibrillators), and selected patients who are likely to be dependent on right
      ventricular pacing. The timing of publication of specific guidelines appears to
      play an essential role in explaining these disparities. CONCLUSIONS: Despite
      general consistency in international guideline recommendations, there remain
      certain patient populations for whom there are variations in recommendations
      concerning eligibility for CRT and selection of the most appropriate device in
      the individual patient.

PMID- 29598933
TI  - The Effect of Door-to-Diuretic Time on Clinical Outcomes in Patients With Acute
      Heart Failure.
AB  - OBJECTIVES: This study sought to examine the impact of door-to-diuretic (D2D)
      time on mortality in patients with acute heart failure (AHF) who were presenting
      to an emergency department (ED). BACKGROUND: Most patients with AHF present with
      congestion. Early decongestion with diuretic agents could improve their clinical
      outcomes. METHODS: The Korea Acute Heart Failure registry enrolled 5,625
      consecutive patients hospitalized for AHF. For this analysis, the study included
      patients who received intravenous diuretic agents within 24 h after ED arrival.
      Early and delayed groups were defined as D2D time <=60 min and D2D time >60 min,
      respectively. The primary outcomes were in-hospital death and post-discharge
      death at 1 month and 1 year on the basis of D2D time. RESULTS: A total of 2,761
      patients met the inclusion criteria. The median D2D time was 128 min
      (interquartile range: 63 to 243 min), and 663 (24%) patients belonged to the
      early group. The baseline characteristics were similar between the groups. The
      rate of in-hospital death did not differ between the groups (5.0% vs. 5.1%; p >
      0.999), nor did the post-discharge 1-month (4.0% vs. 3.0%; log-rank p = 0.246)
      and 1-year (20.6% vs. 19.3%; log-rank p = 0.458) mortality rates. Get With the
      Guidelines-Heart Failure risk score was calculated for each patient. In
      multivariate analyses with adjustment for Get With the Guidelines-Heart Failure
      risk score and other significant clinical covariates and propensity-matched
      analyses, D2D time was not associated with clinical outcomes. CONCLUSIONS: The
      D2D time was not associated with clinical outcomes in a large prospective cohort
      of patients with AHF who were presenting to an ED. (Registry [Prospective Cohort]
      for Heart Failure in Korea [KorAHF]; NCT01389843).

PMID- 29598936
TI  - My LVAD Gave Me a New Lease on Life.

PMID- 29598937
TI  - Changing the Research Culture in the United States.

PMID- 29598938
TI  - There Should Not Be Much Doubt That Neurogenic Stress Cardiomyopathy in Cardiac
      Donors Is a Phenotype of Takotsubo Syndrome.

PMID- 29598939
TI  - Takotsubo Common Pathways and SNRI Medications.

PMID- 29598940
TI  - Solid Organ Transplantation.

PMID- 29598941
TI  - Reply: There Should Not Be Much Doubt That Neurogenic Stress Cardiomyopathy in
      Cardiac Donors Is a Phenotype of Takotsubo Syndrome, and Takotsubo Common
      Pathways and SNRI Medications.

PMID- 29598942
TI  - Reply: Solid Organ Transplantation.

PMID- 29598943
TI  - Heart Rate in Heart Failure With Preserved Ejection Fraction: Another Example of
      the Heterogeneity of This Syndrome.

PMID- 29598945
TI  - Hyperglycemia and risk of adverse outcomes following microvascular reconstruction
      of oncologic head and neck defects.
AB  - INTRODUCTION: Our aim is to examine the correlation between perioperative
      hyperglycemia and post-operative outcomes following microvascular reconstruction
      of head and neck defects. PATIENTS AND METHODS: Retrospective review of a
      prospectively collected database of 350 consecutive patients who underwent
      microvascular reconstruction of malignant head and neck defects over a 2 year
      period. The relationship between perioperative hyperglycemia (>= 180 mg/dL) and
      the incidence of the following complications was evaluated: flap loss, flap
      related complications and surgical site infections (SSI). Sub-group analysis
      based on timing of hyperglycemia was also performed. RESULTS: We identified 313
      patients (89.4%) in the normoglycemic group and 37 patients (10.6%) in the
      hyperglycemic group. Baseline demographics, tumor stage, operative variable were
      comparable. There were no significant differences in flap-related complications
      and overall mortality. SSI were significantly higher in the hyperglycemic cohort
      (48% vs. 28%, p = 0.01). On multivariate analysis, hyperglycemia [OR 2.07; 95%
      CI, 1.87-4.89], perioperative insulin administration [OR 4.805; 95% CI, 2.18
      10.60], prolonged operative time [OR 1.003; 95% CI, 1.002-1.025] and higher
      Charlson co-morbidity indices [II: OR 2.286 & III: OR 2.284] were independent
      predictors of SSI. On sub-group analysis, only patients with early (POD 1) post
      operative hyperglycemia had a significant OR for SSI (OR 1.88; 95% CI, 1.07
      3.29). CONCLUSION: Our findings suggest that perioperative hyperglycemia,
      specifically during the first 24 h post-operatively, is associated with SSI in
      microvascular head and neck reconstruction. This association highlights the need
      for strict screening of head and neck patients for hyperglycemia especially in
      the immediate post-operative period.

PMID- 29598944
TI  - Three-dimensional imaging assessment of anatomic invasion and volumetric
      considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx
      cancer.
AB  - OBJECTIVES: To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and
      extent of involvement of primary tumor on treatment outcomes in a large uniform
      cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal
      preservation strategies. MATERIALS AND METHODS: The pretreatment contrast
      enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma
      were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the
      3D TV and define the extent of invasion. Cartilage and soft tissue involvement
      was coded. The extent of invasion was dichotomized into non/limited invasion
      versus multiple invasion extension (MIE), and was subsequently correlated with
      survival outcomes. RESULTS: The median TV was 6.6 cm3. Sixty-five patients had
      non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was
      52 months. The 5-year local control and overall survival rates for the whole
      cohort were 88% and 68%, respectively. There was no correlation between TV and
      survival outcomes. However, patients with non/limited invasion had better 5-year
      local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a
      significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In
      multivariate correlates of LC, MIE maintained statistical significance whereas
      baseline airway status showed a statistically significance trend with poor LC (p
      = .0087 and 0.06, respectively). Baseline good performance status was an
      independent predictor of improved OS (p = .03) in multivariate analysis.
      CONCLUSION: The extent of primary tumor invasion is an independent prognostic
      factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.

PMID- 29598946
TI  - Cause-specific mortality in patients with head and neck cancer: Long-term follow
      up of a population-based cohort from 1986 to 2012 accounting for competing risks.
AB  - OBJECTIVES: Recent recommendations for treating head and neck cancer (HNC)
      patients favor an individualized approach. Expected long-term survival - together
      with short-term survival - after diagnosis is the primary focus in assessing the
      treatment modality and follow-up scheme. "Disease-specific" survival up to five
      years is often used for measuring the prognosis and for assessing treatment
      methods. However, especially long-term survival is strongly affected by competing
      causes of death among HNC patients. MATERIALS AND METHODS: The long-term
      prognosis of patients with HNC in terms of mortality from both cancer and
      competing causes was analyzed according to recent methodological guidelines by
      examining cumulative incidence functions and models for cause-specific hazards
      and sub-distribution hazards in a population based cohort of 220 patients treated
      in a tertiary care center in Northern Finland. RESULTS: In addition to well-known
      tumor-related factors, mortality from HNC was associated with older age. The
      mortality from other causes of death was strongly dependent on age and Charlson's
      Comorbidity Index, but less on gender. When demonstrating the importance of
      individualized approach in simulated patients, the mortality was highly variable
      across patients with similar cancer status, but with different comorbidities or
      age. CONCLUSION: The overall survival pattern of HNC patients depends not only on
      their cancer characteristics, but also varies greatly according to their age and
      comorbidities. Our findings support the need for individualized treatment and
      follow-up protocols, and active management of comorbid diseases. Appropriate
      methods for analyzing competing risks should be used when presenting survival
      estimates of cancer patients.

PMID- 29598947
TI  - Locoregional extension and patterns of failure for nasopharyngeal carcinoma with
      intracranial extension.
AB  - OBJECTIVE: To evaluate the locoregional extension and patterns of failure for
      nasopharyngeal carcinoma (NPC) with intracranial extension to improve clinical
      target volume (CTV) delineation. PATIENTS AND METHODS: A total of 205 NPC
      patients with intracranial extension by magnetic resonance imaging (MRI) were
      retrospectively reviewed. RESULTS: According to the cumulative incidence rates of
      tumor invasion, we initially classified anatomic sites surrounding the
      nasopharynx into three risk grades: high risk (>=35%), medium risk (>=10-35%),
      and low risk (<10%). It was concluded that the anatomic sites at high risk of
      tumor invasion were the middle/posterior skull base and the anatomic sites
      adjacent to the nasopharynx. The rate of lymph node (LN) metastasis was 90.2%
      (185/205). Retropharyngeal region (RP) and level IIb were the most frequently
      involved regions. Skip metastasis occurred in only 1.6% (3/185). At their last
      follow-up visit, 53 patients (25.9%) had developed treatment failure. Of the 18
      local failures, 12 were considered in-field failure; the other 5 were marginal;
      one of the patients had outside-field failure. Among the 5 patients with marginal
      failures, 4 occurred mainly intracranially, and 1 occurred in the floor and the
      left lateral wall of the nasopharynx. Of the 11 regional failures, 10 were
      considered in-field failures and most of them (8/10) occurred in the unilateral
      upper neck. CONCLUSION: For NPC with intracranial extension, primary disease and
      regional LN spread follow an orderly pattern and LN skipping was unusual.
      Clinical target volume reduction may be feasible for selected patients.

PMID- 29598948
TI  - The impact of HPV status on weight loss and feeding tube use in oropharyngeal
      carcinoma.
AB  - OBJECTIVES: It has been well established that patients with oropharyngeal
      carcinoma are at high nutritional risk, with significant weight loss and tube
      feeding common. Human papillomavirus (HPV)-associated disease has led to a change
      in the "typical" presentation and nutritional profile of this population. The aim
      of our study was to determine whether the need for a feeding tube, and weight
      loss during radiotherapy (RT) in patients with oropharyngeal carcinoma differed
      with HPV status. MATERIALS AND METHODS: Patients who received curative RT +/-
      chemotherapy from January 2011 to January 2016 were included (n = 100). We
      retrospectively evaluated feeding tube use and timing of insertion (prophylactic
      vs reactive), percentage weight loss during RT and the prevalence of critical
      weight loss (CWL) >=5%. RESULTS: HPV-positive patients had significantly higher
      weight loss during RT compared to the rest of the cohort (8.4% vs 6.1%, 95%CI 0.8
      3.9, p = 0.003). CWL was observed in 86% and in a higher proportion with HPV
      positive disease (93%, p = 0.011). Conditional probability modelling analysis
      revealed, with 74% accuracy, concurrent chemoradiotherapy and HPV-positive status
      were predictors of CWL when comparing HPV-positive patients to HPV-negative (96%,
      p = 0.001 and 98%, p = 0.012 respectively). More HPV-positive patients required
      feeding tubes (n = 43, 63%, p = 0.05), most being reactive (n = 27, 63%). All
      patients with reactive tubes experienced CWL. CONCLUSION: The high incidence of
      CWL in patients with HPV-positive oropharyngeal carcinoma is of concern. Tube
      feeding continues to be a necessary nutritional intervention in this population
      and predicting who will require a tube is challenging. Larger, prospective cohort
      studies are required.

PMID- 29598949
TI  - Optimizing the induction chemotherapy regimen for patients with locoregionally
      advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based
      analysis.
AB  - OBJECTIVES: This study aimed at identifying the optimal induction chemotherapy
      regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC)
      treated by intensity-modulated radiotherapy. MATERIALS AND METHODS: We identified
      eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between
      September 2009 and May 2015. Survival outcomes and grade 3-4 toxicities were
      compared between different IC regimen groups. RESULTS: In total, 3738 patients
      were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%)
      receiving TPF, PF and TP, respectively. In the whole population, multivariate
      analysis found that TPF seems to be better than PF and TP. Howerver, subgroup
      analysis revealed TPF and TP had same effectiveness in patients receiving a
      cumulative cisplatin dose (CCD) >=200mg/m2 in concurrent chemotherapy, while TPF
      shows relatively better survival benefit in patients receiving CCD<200mg/m2.
      Grade 3-4 toxicities were similar between TPF and TP groups, but were relatively
      higher than that in PF group. CONCLUSIONS: Our study concluded that induction TP
      regimen may be enough for patients receiving a CCD>=200mg/m2, while TPF may be
      superior to TP and PF for patients receiving a CCD<200mg/m2, although grade 3-4
      toxic events were more common but tolerable. Further studies are needed to
      validate our findings.

PMID- 29598950
TI  - Tumor volume as a predictor of survival in T3 glottic carcinoma: A novel approach
      to patient selection.
AB  - BACKGROUND: The optimal treatment for T3 glottic cancers continues to be debated.
      Organ preservation has become the standard of care, but not all tumors respond
      equally. The purpose of this was to investigate the long-term survival outcomes
      of organ preservation protocols based on tumor volume. METHODS: A retrospective
      review of prospectively collected data from 1966 to 2016 was performed. Patients
      with T3 vocal cord cancer treated with radiation therapy (RT) at the University
      of Florida were included. Local control rates as well as survival rates were
      determined with a Kaplan Meier and Cox regression analysis. Survival was analyzed
      as a function of tumor volume and an optimal cut point was determined. RESULTS:
      107/234 patients were included. 79% received RT and 21% chemo-RT. 5-year local
      control was 61.5% and 5-year disease specific survival was 79.3%. Tumor volume
      was a significant predictor of survival (p = 0.007). An optimal cut point for
      tumor volume was 2.5 cc. Patients with tumor volumes >=2.5 cc had significantly
      worse (p < 0.05) tumor control rates (100% vs. 70.4%). CONCLUSION: Tumor volume
      is a significant predictor of survival outcomes in T3 vocal cord cancers, but
      will need external validation. Tumors <2.5 cc have favorable outcomes. Those with
      higher volume tumors should be counselled appropriately and be considered for
      primary surgical management.

PMID- 29598951
TI  - Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated
      with poor outcome and activation of the YAP pathway.
AB  - OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is
      commonly altered in many human tumors, leading to the activation of p110alpha
      enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA
      alterations such as mutation, gene amplification and overexpression are common in
      head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these
      alterations and clinical outcome are associated, as well as the molecular
      mechanisms involved. MATERIAL AND METHODS: Mutation and copy-number variation in
      PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC
      tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were
      validated in an independent cohort form the University Hospital of A Coruna
      (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110alpha)
      and nuclear YAP were assessed in tissue microarrays in a cohort from the
      University Hospital 12 de Octubre (UH12O, n = 91). RESULTS: Only high expression
      of the PIK3CA gene was associated with poor clinical outcome. The study of gene
      expression, transcription factor and protein signatures suggested that the
      activation of the Hippo-YAP pathway, involved in organ size, stem cell
      maintenance and tumorigenesis, could underlie tumor progression in PI3KCA
      overexpressing tumors. Tissue arrays showed that PI3K p110alpha levels correlated
      with YAP nuclear localization in HNSCC tumors. CONCLUSIONS: High expression of
      PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence.
      In these tumors, progression could rely on the Hippo-YAP pathway instead of the
      canonical Akt/mTOR pathway. This observation could have important implications in
      the therapeutic options for patients.

PMID- 29598952
TI  - Upfront surgery versus definitive chemoradiotherapy in patients with human
      Papillomavirus-associated oropharyngeal squamous cell cancer.
AB  - OBJECTIVES: Currently, human papillomavirus-associated oropharyngeal squamous
      cell carcinoma (HPV-A OPC) is managed with either primary surgery or definitive
      chemoradiotherapy (CRT), despite the lack of supporting randomized prospective
      data. We therefore assessed the outcomes of each treatment strategy using the
      National Cancer Database (NCDB). METHODS: The NCDB was used to identify patients
      diagnosed with cT1 N2a-2b or cT2 N1-2b HPV-A OPC from 2010 to 2013 who underwent
      treatment with primary surgery or CRT. Demographic and clinicopathologic
      predictors of treatment were analyzed by the chi-square test and logistic
      regression. Overall survival (OS) was evaluated using multivariable Cox
      proportional hazard regression, Kaplan-Meier, log-rank test, and propensity score
      matched analysis. RESULTS: We identified 3063 patients; 1576 (51.5%) received CRT
      and 1487 (48.5%) underwent primary surgery. Median follow up was 32 months. 972
      (65.4%) surgical patients received adjuvant CRT. On multivariable Cox regression,
      3-year OS was comparable between surgery and CRT (hazard ratio [HR] 1.08, 95%
      confidence interval [CI] 0.83-1.41, P = 0.58). Inferior OS was significantly
      associated with increasing clinical T and N stage, older age, and non-private
      insurance. Propensity score-matching yielded a 2526 patient cohort and
      redemonstrated similar OS (HR, 1.09; 95% CI 0.81-1.47; P = 0.55). Comparable
      outcomes persisted in a subset analysis of patients with margin-negative
      resection, with 3-year OS 90.8% in CRT patients vs. 93.6% in surgery patients
      (log-rank P = 0.27). CONCLUSIONS: Upfront surgery and CRT yielded comparable 3
      year OS outcomes in this cohort. In this national sample, 65.4% of surgical
      patients received trimodal therapy with adjuvant CRT, highlighting the need for
      improved patient selection for primary surgery.

PMID- 29598953
TI  - Chemoradiotherapy using retrograde superselective intra-arterial infusion for
      tongue cancer: Analysis of therapeutic results in 118 cases.
AB  - OBJECTIVES: To evaluate the therapeutic results and rate of organ preservation in
      patients with squamous cell carcinoma of the tongue treated with retrograde
      superselective intra-arterial chemoradiotherapy. MATERIALS AND METHODS: Between
      June 2006 and June 2015, 118 patients with tongue cancer were treated with intra
      arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50-70 Gy)
      and daily concurrent intra-arterial chemotherapy (docetaxel, total 50-70 mg/m2;
      cisplatin, total 125-175 mg/m2) for 5-7 weeks. Locoregional control and overall
      survival rates were calculated by the Kaplan-Meier method. Cox's proportional
      hazards model was used for both univariate and multivariate analyses. RESULTS:
      The median follow-up for all patients was 38.5 months (range, 3-129 months).
      After intra-arterial chemoradiotherapy, primary site complete response was
      achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall
      survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities
      included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included
      anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in
      45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity
      consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients.
      On univariate analysis, T stage and overall stage were significantly associated
      with locoregional control, and N stage and overall stage were significantly
      associated with overall survival. On multivariate analysis, the only significant
      predictor of overall survival was overall stage classification. CONCLUSION:
      Retrograde superselective intra-arterial chemoradiotherapy for tongue cancer
      provided good overall survival and locoregional control.

PMID- 29598954
TI  - Clinical outcomes and prognostic factors in cisplatin versus cetuximab
      chemoradiation for locally advanced p16 positive oropharyngeal carcinoma.
AB  - OBJECTIVES: Randomized trials evaluating cisplatin versus cetuximab
      chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report
      preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the
      off-trial use of cetuximab in p16+ patients is increasing, even in those who
      could potentially tolerate cisplatin. The purpose of this study was to compare
      the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and
      to identify prognostic factors and predictors of tumor response. MATERIALS AND
      METHODS: Cases of p16+ OPC treated with cisplatin or cetuximab CRT at our
      institution from 2010 to 2014 were identified. Recursive partitioning analysis
      (RPA) classification was used to determine low-risk (LR-RPA) and intermediate
      risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used
      to compare groups. RESULTS: We identified 205 patients who received cisplatin (n
      = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n
      = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year
      locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival
      (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and
      overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001].
      Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and
      IR-RPA (97.1 vs 80.3%, p < .001) groupings. CONCLUSION: When treating p16+ OPC
      with CRT, the threshold for substitution of cisplatin with cetuximab should be
      maintained appropriately high in order to prolong survival times and optimize
      locoregional and distant tumor control. When cetuximab is used in cisplatin
      ineligible patients, altered fractionation RT should be considered in an effort
      to improve LRC.

PMID- 29598955
TI  - Prognostic Impact of Weight Change During Adjuvant Chemotherapy in Patients With
      High-Risk Early Breast Cancer: Results From the ADEBAR Study.
AB  - BACKGROUND: In addition to established prognostic factors, individual lifestyle
      associated factors, such as obesity, physical activity, and diet, seem to
      modulate the course of breast cancer. The aim of this analysis was to evaluate
      the influence of weight changes during adjuvant chemotherapy on outcome in a
      large multicenter prospectively randomized trial. PATIENTS AND METHODS: The
      ADEBAR trial compares a sequential chemotherapy consisting of
      epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5
      fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early
      breast cancer. Body weight was measured before each cycle of chemotherapy.
      According to the relative weight change (>= 5%) between the first and the last
      cycle, patients were categorized into the weight gain, weight loss, or stable
      weight group. Overall survival (OS) and disease-free survival were assessed by
      univariate Kaplan-Meier and multivariate Cox regression analyses. RESULTS:
      Concise data from 1080 of 1493 participants who completed all cycles of
      chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight
      changed by >= 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight.
      Multivariate analysis showed a significant independent effect of weight change on
      OS (P = .039), but not on disease-free survival (P = .111). Both weight change
      groups had a worse OS compared to patients with stable weight (weight gain:
      hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss:
      hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067). CONCLUSION: Weight change of >
      5% during adjuvant chemotherapy in patients with high-risk early breast cancer is
      associated with poor OS.

PMID- 29598956
TI  - Model based PI power system stabilizer design for damping low frequency
      oscillations in power systems.
AB  - This paper explores a two-level control strategy by blending local controller
      with centralized controller for the low frequency oscillations in a power system.
      The proposed control scheme provides stabilization of local modes using a local
      controller and minimizes the effect of inter-connection of sub-systems
      performance through a centralized control. For designing the local controllers in
      the form of proportional-integral power system stabilizer (PI-PSS), a simple and
      straight forward frequency domain direct synthesis method is considered that
      works on use of a suitable reference model which is based on the desired
      requirements. Several examples both on one machine infinite bus and multi-machine
      systems taken from the literature are illustrated to show the efficacy of the
      proposed PI-PSS. The effective damping of the systems is found to be increased
      remarkably which is reflected in the time-responses; even unstable operation has
      been stabilized with improved damping after applying the proposed controller. The
      proposed controllers give remarkable improvement in damping the oscillations in
      all the illustrations considered here and as for example, the value of damping
      factor has been increased from 0.0217 to 0.666 in Example 1. The simulation
      results obtained by the proposed control strategy are favourably compared with
      some controllers prevalent in the literature.

PMID- 29598957
TI  - Pharmacovigilance in pediatrics.
AB  - The characteristics of pharmacology and drug evaluation in the pediatric age
      group highlight the necessity for the pharmacovigilance community to adjust to
      the specific features of children. At the time of marketing a medicinal product
      intended for children, the product's safety profile is sometimes less well known
      than for adults due to fewer or small sample clinical trials. Furthermore, the
      frequent off-labeled drug use, the use of unsuitable dosage forms and the need
      for continuous dose adjustments increase the risk of medication errors and thus
      lead to avoidable adverse drug reactions (ADRs). The occurrence of child-specific
      ADRs (such as growth disorders) or ADRs more commonly occurring in children than
      in adults make it necessary to monitor the safety of child-specific drugs.
      Pediatric pharmacovigilance includes also the consequences of in utero exposure,
      whether manifestations are present from birth or occur in early childhood (such
      as neurodevelopmental disorders). The incidence of ADRs varies with age, setting
      of medical care (in- or out-patients, pediatric specialties) and by country in
      which the study was carried out. The drugs most frequently reported with ADRs are
      those most commonly used in the pediatric age group, i.e. antibiotics and
      vaccines. The ADRs most often reported are skin, neurological and general
      disorders. As in adults, spontaneous notification is essential to generate alerts
      and child-specific pharmacoepidemiological studies are necessary and should be
      developed.

PMID- 29598958
TI  - Drug-induced chronic liver injury.

PMID- 29598959
TI  - Morbidity and mortality of acute renal failure in the Critical Care Unit of a
      regional hospital.
AB  - OBJECTIVES: The main objective of the study is to perform an analysis on the
      incidence, predictive variables, and severity of acute kidney injury (AKI) and
      its impact on the morbidity and mortality of patients in the Resuscitation and
      Special Care Unit (RSCU) of a regional hospital. METHODS: A retrospective
      observational study was conducted that included all patients admitted from 1
      January 2012 to 1 January 2015 (1,115 patients). The follow-up was until 15 July
      2015. A descriptive statistical analysis of clinical-epidemiological and
      analytical variables was carried out. An analysis was then performed AKI in RSCU
      and mortality, as well as the agreement between the RIFLE (Risk, Injury, Failure,
      Loss of Kidney Function, and End-stage Kidney Disease)/AKIN (Acute Kidney Injury
      Network)/KDIGO (Kidney Disease: Improving Global Outcomes) criteria (kappa
      index). A multivariate logistic regression analysis was performed to select the
      variables associated with the presentation of AKI in RSCU and a univariate
      (Kaplan-Meier) and multivariate survival analysis (Cox regression). The
      statistical analysis was carried out using the statistical package SPSS 21.
      RESULTS: During admission to RSCU, 486 patients presented with AKI (43.6%), of
      which 21% were in stage I, 13.8% in stage II, and in stage III 8.7%. A high level
      of agreement was observed between the RIFLE/AKIN/KDIGO criteria. The variables
      that were related to the presence of AKI, are male (OR: 1.37; 95% CI: 1.02-2.30),
      to high Charlson comorbidity index (OR: 1.17; 95% CI: 1.09-1.26), carriers of
      chronic kidney disease (OR: 5.99; 95% CI: 4.58-8.18), admission due to surgery
      (OR: 1.69; 95% CI: 1.24-2.30), and shock (OR: 4.70; 95% CI: 3.34-6.61). The
      probability of survival during admission in RSCU decreases in patients with AKI
      (HR: 5.44; 95% CI: 1.70-17.39), and as the individual severity index of Liano
      increases (HR: 10.29; 95% CI: 3.34-31.76). The probability of survival at the end
      of follow-up after hospital discharge decreases in patients with AKI (HR: 1.72;
      95% CI: 1.14-2.61), as the individual severity index of Liano increases (HR: 9,6;
      95% CI: 5.07-18.20), the Charlson comorbidity index>6 (HR: 1.09; 95% CI: 1.03
      1.15), low serum albumin<2.5mg/dL (HR: 1.69; 95% CI: 1.13-2.53), age by year>70
      years (HR: 1.03; 95% CI: 1.01-1.04), males (HR: 1.38; 95% CI: 1.06-1.79) and
      carriers of previous chronic kidney disease (HR: 1.56; 95% CI: 1.02-2.38).
      CONCLUSIONS: This study shows the presentation of an episode of AKI was an
      independent factor associated both with mortality during admission to RSCU, and
      later after hospital discharge. It is necessary to know the risk factors of this
      complication in order to adopt preventive measures.

PMID- 29598960
TI  - Older people living with chronic illness.
AB  - This study aimed to gain a better understanding of what it is like for older
      people to live with chronic illness. A Phenomenological method was used. A
      purposive sampling strategy was used to recruit older people with chronic illness
      from one community in Nakhonratchasima province, Thailand. Semi-structured
      interview guides were used to explore the participants' experiences and
      perceptions. Data saturation was reached after 30 interviews were completed. The
      data was analyzed using thematic analysis. Four themes emerged from the data: 1)
      living a restricted life, 2) feeling overwhelmed, 3) understanding and accepting
      loss, and 4) being kind to oneself and learning to live with the disease. The
      findings may increase understanding about what older people with chronic illness
      experience. Health care providers can use this understanding to relate health
      care and guidance to their patients by incorporating cultural influences and
      religious/spiritual beliefs into the standardized care for this population.

PMID- 29598961
TI  - 20-MHz Ultrasound for Measurements of Flow-Mediated Dilation and Shear Rate in
      the Radial Artery.
AB  - A high-frequency scanning system consisting of a 20-MHz linear array transducer
      combined with a 20-MHz pulsed Doppler probe was introduced to evaluate the degree
      of radial artery flow-mediated dilation (FMD [%]) in two groups of patients after
      5 min of controlled forearm ischemia followed by reactive hyperemia. In group I,
      comprising 27 healthy volunteers, FMD (mean +/- standard deviation) was 15.26 +/-
      4.90% (95% confidence interval [CI]: 13.32%-17.20%); in group II, comprising 17
      patients with chronic coronary artery disease, FMD was significantly less at 4.53
      +/- 4.11% (95% CI: 2.42%-6.64%). Specifically, the ratio FMD/SR (mean +/-
      standard deviation), was equal to 5.36 * 10-4 +/- 4.64 * 10-4 (95% CI: 3.54 * 10
      4 to 7.18 * 10-4) in group I and 1.38 * 10-4 +/- 0.89 * 10-4 (95% CI: 0.70 * 10-4
      to 2.06 * 10-4) in group II. Statistically significant differences between the
      two groups were confirmed by a Wilcoxon-Mann-Whitney test for both FMD and FMD/SR
      (p <0.01). Areas under receiver operating characteristic curves for FMD and
      FMD/SR were greater than 0.9. The results confirm the usefulness of the proposed
      measurements of radial artery FMD and SR in differentiation of normal patients
      from those with chronic coronary artery disease.

PMID- 29598963
TI  - Abstracts of the 2018 Pediatric Endocrinology Nursing Society Conference.

PMID- 29598962
TI  - Sources of Variability in the Detection of B-Lines, Using Lung Ultrasound.
AB  - Lung ultrasound (LUS) is a largely employed diagnostic tool but an operational
      protocol for implementation has never been proposed. The lack of standardization
      clearly introduces variability in LUS results. We enrolled adult patients
      presenting for acute dyspnea with a clinical suspect of etiology related to heart
      failure. We calculated agreement among four providers in assessing B-lines. We
      varied probes, depth, evaluation time and scanning areas and we estimated the
      importance of each factors on B-lines assessment. Overall agreement among raters
      varied from a kappa of 0.70 to 0.81. The mean number of B-lines was 5.44 (95%
      confidence interval, CI, 4.1-6.8). This estimate did not suffer variation by the
      depth used (0.03, 95% CI -0.2-0.2, more B-lines, using 19 cm versus 10 cm). The
      use of a convex probe and expertise in LUS reduced the number of artifacts by 1.7
      (95% CI 1.5-1.9) and 1.1 in comparison with a phased array probe and naive
      operators. Evaluation time increased estimates by 1.2 (95% CI 1-1.5) and 2.9 (95%
      CI 2.7-3.9) B-lines for 4" and 7" clips (reference was 2" clips). This study
      suggests that the probe, the evaluation time and the level of expertise might
      affect the results of quantitative assessment of B-lines.

PMID- 29598964
TI  - Patient feedback questionnaires to enhance consultation skills of healthcare
      professionals: A systematic review.
AB  - OBJECTIVE: To identify patient feedback questionnaires that assess the
      development of consultation skills (CSs) of practitioners. METHODS: We conducted
      a systematic search using seven databases from inception to January 2017 to
      identify self-completed patient feedback questionnaires assessing and enhancing
      the development of CSs of individual practitioners. Results were checked for
      eligibility by three authors, and disagreements were resolved by discussion.
      Reference lists of relevant studies and Open Grey were searched for additional
      studies. RESULTS: Of 16,312 studies retrieved, sixteen were included, describing
      twelve patient feedback questionnaires that were mostly designed for physicians
      in primary care settings. Most questionnaires had limited data regarding their
      psychometric properties, except for the Doctor Interpersonal Skills Questionnaire
      (DISQ). Most studies conducted follow-up, capturing positive views of
      practitioners regarding the process (n = 14). Feedback was repeated by only three
      studies, demonstrating different levels of improvement in practitioners'
      performance. CONCLUSION: Identified questionnaires were mainly focused on
      physicians, however, to support using patient feedback, questionnaires need to be
      validated with other practitioners. PRACTICE IMPLICATIONS: Several patient
      feedback questionnaires are available, showing potential for supporting
      practitioners' development. Valid questionnaires should be used with appropriate
      practitioners in developing more evidence for the impact they may have on actual
      consultations.

PMID- 29598965
TI  - Validation of the health literacy scale for diabetes as a criterion-referenced
      test with standard setting procedures.
AB  - OBJECTIVE: To develop and examine the psychometric properties of the Korean
      Health Literacy Scale for Diabetes Mellitus (KHLS-DM), and to establish
      reasonable cutoff scores. METHODS: Initially, 299 items were generated to measure
      diabetes-related words, numeracy, and information utilization. Content validity
      assessment and preliminary tests were conducted. After exploratory factor
      analysis (EFA) and Rasch analysis, the remaining 65 items were administered to a
      quota sample of 500 diabetic patients aged 40-74 years. The items were narrowed
      down to 58 items based on an item fit index. To obtain cutoff scores, Jaeger's
      method and the Bookmark method were employed. RESULTS: A confirmatory factor
      analysis (CFA) was performed, and a three-factor model was supported (chi2/df =
      3.891, CFI = 0.92, TLI = 0.91, RMSEA = 0.04). The overall scores ranged from 0 to
      58, and two cutoff points were established. The scale exhibited good internal
      consistency (Cronbach's alpha = 0.83). CONCLUSIONS: The KHLS-DM is a reliable and
      valid measure with cutoff points to classify individuals into three groups
      (adequate, marginal, and inadequate). PRACTICE IMPLICATIONS: The standard setting
      may be useful for researchers to validate health literacy measures in other
      countries and populations.

PMID- 29598966
TI  - Comments and question on "Selective inhibition of endothelial NF-kappaB signaling
      attenuates chronic intermittent hypoxia-induced atherosclerosis in mice".

PMID- 29598967
TI  - Surveillance of sexualised drug use - the challenges and the opportunities.
AB  - Sexualised drug use (SDU), the use of drugs in a sexual context, has emerged as a
      marker of high-risk sexual activity and poor sexual health among gay, bisexual
      and other men who have sex with men, however, there are no robust estimates of
      the prevalence of SDU. The primary sources of surveillance data on SDU should
      include both sexual health and drug treatment services. The challenges to
      achieving comprehensive, timely and valid SDU surveillance include establishing
      case definitions, selecting appropriate surveillance settings, and normalising
      the monitoring of SDU at clinical services. In this commentary we propose a means
      to address these challenges and discuss other sources of SDU data from ad hoc
      population surveys and sentinel systems. We also present case studies of SDU
      surveillance development in England and Switzerland. The patterns of SDU will be
      affected by a rapidly changing drug market and, as a result, surveillance systems
      must continuously adapt to ensure that they are fit for purpose and can provide
      data to guide policy.

PMID- 29598968
TI  - [Hospital medical doctors perception on palliative home care support team].

PMID- 29598969
TI  - [Changes in the perception of medical students towards Geriatrics after a
      clinical-teaching rotation].

PMID- 29598970
TI  - [Pharmacological prevention of delirium: A long way to go].

PMID- 29598971
TI  - [Gastrointestinal endoscopy in patients of advanced age].
AB  - The dramatic increase in life expectancy is leading to a significant increase in
      the use of gastrointestinal endoscopy in the elderly. Taking into account these
      demographic changes, the use of gastrointestinal endoscopy in this age group is
      of great importance. Although these procedures are generally safe and well
      tolerated even in very elderly patients, the onset of physiological changes
      associated with aging and the increased prevalence of cardiovascular and
      pulmonary comorbidities raise the risk of sedation related complications in these
      patients. Age alone is not a contraindication for performing any endoscopic
      procedure. However, elderly patients have their own peculiarities that require a
      detailed review of the characteristics, risks and benefits of endoscopic
      procedures in this specific context.

PMID- 29598972
TI  - [Digoxin in reduced heart failure and sinus rhythm. When should it be indicated
      in 2018?]

PMID- 29598973
TI  - How Patient-Centered Outcomes Research is Connected to HIV Nursing.

PMID- 29598974
TI  - beta-lapachone and alpha-nor-lapachone modulate Candida albicans viability and
      virulence factors.
AB  - BACKGROUND: Candida albicans is the most important fungal pathogen that causes
      infections in humans, and the search for new therapeutic strategies for its
      treatment is essential. OBJECTIVE: The aim of this study was to evaluate the
      activity of seven naphthoquinones (beta-lapachone, beta-nor-lapachone, bromide
      beta-lapachone, hydroxy-beta-lapachone, alpha-lapachone, alpha-nor-lapachone and
      alpha-xyloidone) on the growth of a fluconazole-resistant C. albicans oral
      clinical isolate and the effects of these compounds on the viability of mammalian
      cells, on yeast's morphogenesis, biofilm formation and cell wall mannoproteins
      availability. RESULTS: All the compounds were able to completely inhibit the
      yeast growth. beta-lapachone and alpha-nor-lapachone were the less cytotoxic
      compounds against L929 and RAW 264.7 cells. At IC50, beta-lapachone inhibited
      morphogenesis in 92%, while the treatment of yeast cells with alpha-nor-lapachone
      decreased yeast-to-hyphae transition in 42%. At 50MUg/ml, beta-lapachone
      inhibited biofilm formation by 84%, whereas alpha-nor-lapachone reduced biofilm
      formation by 64%. The treatment of yeast cells with beta-lapachone decreased cell
      wall mannoproteins availability in 28.5%, while alpha-nor-lapachone was not able
      to interfere on this virulence factor. Taken together, data show that beta
      lapachone and alpha-nor-lapachone exhibited in vitro cytotoxicity against a
      fluconazole-resistant C. albicans strain, thus demonstrating to be promising
      candidates to be used in the treatment of infections caused by this fungus.

PMID- 29598975
TI  - Use of modified Richards model to predict isothermal and non-isothermal microbial
      growth.
AB  - Mathematical models are often used to predict microbial growth in food products.
      An important class of these models involves the adaptation of classical sigmoid
      functions, such as the Gompertz and logistic functions. This study aimed to
      validate the use of the modified Richards model in various situations, which have
      not previously been tested. The model was obtained through solving a system of
      two differential equations and could be applied to both isothermal and non
      isothermal environments. To test and validate this model, we used published
      datasets containing data for the growth of Pseudomonas spp. in fish products. The
      results obtained after fitting the model showed that it could be effectively used
      to describe and predict the Pseudomonas growth curves under various temperature
      regimens. However, the influence of the shape parameter on the growth curve is an
      issue that needs further evaluation.

PMID- 29598976
TI  - Phylogenetic MLSA and phenotypic analysis identification of three probable novel
      Pseudomonas species isolated on King George Island, South Shetland, Antarctica.
AB  - Antarctica harbors a great diversity of microorganisms, including bacteria,
      archaea, microalgae and yeasts. The Pseudomonas genus is one of the most diverse
      and successful bacterial groups described to date, but only eight species
      isolated from Antarctica have been characterized. Here, we present three
      potentially novel species isolated on King George Island. The most abundant
      isolates from four different environments, were genotypically and phenotypically
      characterized. Multilocus sequence analysis and 16S rRNA gene analysis of a
      sequence concatenate for six genes (16S, aroE, glnS, gyrB, ileS and rpoD),
      determined one of the isolates to be a new Pseudomonas mandelii strain, while the
      other three are good candidates for new Pseudomonas species. Additionally,
      genotype analyses showed the three candidates to be part of a new subgroup within
      the Pseudomonas fluorescens complex, together with the Antarctic species
      Pseudomonas antarctica and Pseudomonas extremaustralis. We propose terming this
      new subgroup P. antarctica. Likewise, phenotypic analyses using API 20 NE and
      BIOLOG(r) corroborated the genotyping results, confirming that all presented
      isolates form part of the P. fluorescens complex. Pseudomonas genus research on
      the Antarctic continent is in its infancy. To understand these microorganisms'
      role in this extreme environment, the characterization and description of new
      species is vital.

PMID- 29598977
TI  - "You Aren't Going to Cut On Me!" Urgent Medical Decisions for Patients With
      Schizophrenia.

PMID- 29598978
TI  - Normal values of 3 methods to determine patellar height in children from 6 to 12
      years.
AB  - : The aim of the study was to compare three methods for high-score measurement in
      children, Caton-Deschamps, Blackburne-Peel and Koshino-Sugimoto, to determine the
      normal value of each method in a group of normal children. MATERIALS AND METHODS:
      A cross-sectional study on knee x-rays of normal children. Three orthopaedic
      surgeons measured the Caton-Deschamps, Blackburne-Peel and Koshino-Sugimoto
      indices. Concordance was assessed using the intraclass correlation coefficient.
      For interobserver variability, the measurements of each observer for each index
      were compared and for intraobserver variability, the coefficient between the 2
      measurements was calculated by the same observer at 2 different times. RESULTS:
      140 knee X-rays divided into 4 age groups were obtained. For the Blackburne-Peel
      index, an average median of the 3 observers was obtained of 1.07 and with P5-P95
      (0.76-1.60). For the Caton-Deschamps index, an average median of the three
      observers of 1.22 was obtained and with P5-P95 (0.91-1.70). For the Koshino
      Sugimoto index, we obtained an average median of the 3 observers of 1.16 and with
      P5-P95 (0.99-1.36). DISCUSSION: This study shows that the Koshino-Sugimoto index
      had the highest reliability, reproducibility and similarity in the population
      studied, both intra-observer and inter-observer. The other methods evaluated also
      had variability indices to be taken into account, but were inferior to the
      Koshino-Sugimoto index.

PMID- 29598979
TI  - Considering developing a specialized epilepsy employment program? The PEP Jobs
      Program paradigm.

PMID- 29598980
TI  - A Profile of Dennis Lo, DM, DPhil, FRCP, FRCPath, FRS.

PMID- 29598982
TI  - Re: Peter Strom, Tobias Nordstrom, Henrik Gronberg, Martin Eklund. The Stockholm
      3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution,
      and Reflex Test Potential. Eur Urol. In press.
      https://doi.org/10.1016/j.eururo.2017.12.028.

PMID- 29598983
TI  - The Androgen Signaling Axis and Risk Stratification for High-grade Prostate
      Cancer.

PMID- 29598981
TI  - Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low
      risk Prostate Cancer: A Mixed-method Systematic Review.
AB  - CONTEXT: Despite support for active surveillance (AS) as a first treatment choice
      for men with low-risk prostate cancer (PC), this strategy is largely
      underutilised. OBJECTIVE: To systematically review barriers and facilitators to
      selecting and adhering to AS for low-risk PC. EVIDENCE ACQUISITION: We searched
      PsychINFO, PubMed, Medline 2000-now, Embase, CINAHL, and Cochrane Central
      databases between 2002 and 2017 using the Preferred Reporting Items for
      Systematic Review and Meta-analysis (PRISMA) statement. The Purpose, Respondents,
      Explanation, Findings and Significance (PREFS) and Strengthening the Reporting of
      Observational Studies in Epidemiology (STROBE) quality criteria were applied.
      Forty-seven studies were identified. EVIDENCE SYNTHESIS: Key themes emerged as
      factors influencing both choice and adherence to AS: (1) patient and tumour
      factors (age, comorbidities, knowledge, education, socioeconomic status, family
      history, grade, tumour volume, and fear of progression/side effects); (2) family
      and social support; (3) provider (speciality, communication, and attitudes); (4)
      healthcare organisation (geography and type of practice); and (5) health policy
      (guidelines, year, and awareness). CONCLUSIONS: Many factors influence men's
      choice and adherence to AS on multiple levels. It is important to learn from the
      experience of other chronic health conditions as well as from
      institutions/countries that are making significant headway in appropriately
      recruiting men to AS protocols, through standardised patient information,
      clinician education, and nationally agreed guidelines, to ultimately decrease
      heterogeneity in AS practice. PATIENT SUMMARY: We reviewed the scientific
      literature for factors affecting men's choice and adherence to active
      surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use
      of AS could be increased by addressing a variety of factors such as information,
      psychosocial support, clinician education, and standardised guidelines.

PMID- 29598984
TI  - Reply to Ola Bratt and Anna Ofverholm's Letter to the Editor re: Peter Strom,
      Tobias Nordstrom, Henrik Gronberg, Martin Eklund. The Stockholm-3 Model for
      Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex
      Test Potential. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2017.12.028.

PMID- 29598985
TI  - Re: Jinjing Chen, Ilaria Guccini, Diletta Di Mitri, et al. Compartmentalized
      Activities of the Pyruvate Dehydrogenase Complex Sustain Lipogenesis in Prostate
      Cancer. Nat Genet 2018;50:219-28: Lipid Metabolism in Prostate Cancer: Expanding
      Patient Therapeutic Opportunities.

PMID- 29598986
TI  - Rhythmical massage improves autonomic nervous system function: a single-blind
      randomised controlled trial.
AB  - BACKGROUND: Rhythmical massage therapy (RMT) is a massage technique used in
      anthroposophic medicine. OBJECTIVE: The authors aimed to investigate the
      physiological action of RMT on the cardiovascular system by analysing heart rate
      variability (HRV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This study was
      a randomised, controlled and single-blinded trial, involving 44 healthy women
      (mean age: (26.20 +/- 4.71) years). The subjects were randomised to one of three
      arms: RMT with aromatic oil (RA), RMT without aromatic oil (RM) or standardised
      sham massage (SM). In the study the subjects were exposed to a standardised
      stress situation followed by one of the study techniques and Holter
      electrocardiograms (ECGs) were recorded for 24 h. MAIN OUTCOME MEASURES: HRV
      parameters were calculated from linear (time and frequency domain) and nonlinear
      dynamics (symbolic dynamics, Poincare plot analysis) of the 24-h Holter ECG
      records. RESULTS: Short- and long-term effects of massage on autonomic regulation
      differed significantly among the three groups. Immediately after an RMT session,
      stimulation of HRV was found in the groups RA and RM. The use of an aromatic oil
      produced greater short-term measurable changes in HRV compared with rhythmic
      massage alone, but after 24 h the effect was no longer distinguishable from the
      RM group. The lowest stimulation of HRV parameters was measured in the SM group.
      CONCLUSION: RMT causes specific and marked stimulation of the autonomic nervous
      system. Use of a medicinal aromatic oil had only a temporary effect on HRV,
      indicating that the RM causes the most relevant long-term effect. The effect is
      relatively specific, as the physiological effects seen in the group of subjects
      who received only SM were considerably less pronounced. TRIAL REGISTRATION:
      Registration trial DRKS00004164 on DRKS.

PMID- 29598987
TI  - Response to letter from Dr. Madias.

PMID- 29598988
TI  - "In this together": Social identification predicts health outcomes (via self
      efficacy) in a chronic disease self-management program.
AB  - RATIONALE: Self-management programs are an established approach to helping people
      cope with the challenges of chronic disease, but the psychological mechanisms
      underlying their effectiveness are not fully understood. A key assumption of self
      management interventions is that enhancing people's self-efficacy (e.g., via the
      development of relevant skills and behaviours) encourages adaptive health-related
      behaviors and improved health outcomes. However, the group-based nature of the
      programs allows for the possibility that identification with other program
      members is itself a social psychological platform for positive changes in illness
      related confidence (i.e., group-derived efficacy) and physical and mental health.
      METHOD: The researchers evaluated this hypothesis in a telehealth version of a
      chronic disease self-management program delivered in 13 rural and remote
      communities in northern Ontario, Canada (September 2007 to June 2008).
      Participants were 213 individuals with a self-reported physician diagnosis of
      chronic lung disease, heart disease, stroke, or arthritis. Measures of social
      identification, group-derived efficacy, and individual efficacy were administered
      seven weeks after baseline, and mental and physical health outcomes (health
      distress, psychological well-being, depression, vitality, pain, role limits, and
      disability) were assessed at four months. RESULTS: Structural equation modeling
      indicated that social identification was a positive predictor of group-derived
      efficacy and (in turn) individual self-efficacy (controlling for baseline), which
      was significantly associated with better physical and mental health outcomes.
      CONCLUSION: The results are consistent with growing evidence of the value of a
      social identity-based approach in various health and clinical settings. The
      success of chronic disease self-management programs could be enhanced by
      attending to and augmenting group identification during and after the program.

PMID- 29598989
TI  - Facial Calcinosis Cutis in a Woman with Paraneoplastic Dermatomyositis.

PMID- 29598990
TI  - Usefulness of 2% Topical Diltiazem in Chondrodermatitis Nodularis Helicis: A
      Report of 2 Cases.

PMID- 29598991
TI  - Erythematous Pedunculated Papule on the Knee.

PMID- 29598992
TI  - Urticarial Dermatitis. A Cutaneous Reaction Pattern.

PMID- 29598993
TI  - Nonvenereal Sclerosing Lymphangitis of the Penis: Importance of the Clinical
      Diagnosis.

PMID- 29598994
TI  - Allergic Contact Dermatitis Due to Methyl Glucose Dioleate in a Balm Cream.

PMID- 29598995
TI  - Reprint of "CON4EI: Bovine Corneal Opacity and Permeability (BCOP) test for
      hazard identification and labelling of eye irritating chemicals".
AB  - Assessment of ocular irritation potential is an international regulatory
      requirement in the safety evaluation of industrial and consumer products. None in
      vitro ocular irritation assays are capable of fully categorizing chemicals as
      stand-alone. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium assessed the
      reliability of eight in vitro test methods and computational models as well as
      established a tiered-testing strategy. One of the selected assays was Bovine
      Corneal Opacity and Permeability (BCOP). In this project, the same corneas were
      used for measurement of opacity using the OP-KIT, the Laser Light-Based
      Opacitometer (LLBO) and for histopathological analysis. The results show that the
      accuracy of the BCOP OP-KIT in identifying Cat 1 chemicals was 73.8% while the
      accuracy was 86.3% for No Cat chemicals. BCOP OP-KIT false negative results were
      often related to an in vivo classification driven by conjunctival effects only.
      For the BCOP LLBO, the accuracy in identifying Cat 1 chemicals was 74.4% versus
      88.8% for No Cat chemicals. The BCOP LLBO seems very promising for the
      identification of No Cat liquids but less so for the identification of solids.
      Histopathology as an additional endpoint to the BCOP test method does not reduce
      the false negative rate substantially for in vivo Cat 1 chemicals.

PMID- 29598996
TI  - Reprint of "CON4EI: Selection of the reference chemicals for hazard
      identification and labelling of eye irritating chemicals".
AB  - Assessment of the acute eye irritation potential is part of the international
      regulatory requirements for testing of chemicals. In the past, several
      prospective and retrospective validation studies have taken place in the area of
      serious eye damage/eye irritation testing. Success in terms of complete
      replacement of the regulatory in vivo Draize rabbit eye test has not yet been
      achieved. A very important aspect to ensure development of successful alternative
      test methods and/or strategies for serious eye damage/eye irritation testing is
      the selection of appropriate reference chemicals. A set of 80 reference chemicals
      was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye
      Irritation testing strategy) project, in collaboration with Cosmetics Europe,
      from the Draize Reference Database published by Cosmetics Europe based on key
      criteria that were set in their paper (e.g. balanced by important driver of
      classification and physical state). The most important goals of the CON4EI
      project were to identify the performance of eight in vitro alternative tests in
      terms of driver of classification and to identify similarities/differences
      between the methods in order the build a successful testing strategy that can
      discriminate between all UN GHS categories. This paper provides background on
      selection of the test chemicals.

PMID- 29598997
TI  - Unravelling the adaptation strategies employed by Glaciozyma antarctica PI12 on
      Antarctic sea ice.
AB  - Glaciozyma antarctica PI12, is a psychrophilic yeast isolated from Antarctic sea.
      In this work, Expressed Sequence Tags (EST) from cells exposed to three different
      temperatures; 15  degrees C, 0  degrees C and -12  degrees C were generated to
      identify genes associated with cold adaptation. A total of 5376 clones from each
      library were randomly picked and sequenced. Comparative analyses from the
      resulting ESTs in each condition identified several groups of genes required for
      cold adaptation. Additionally, 319 unique transcripts that encoded
      uncharacterised functions were identified in the -12  degrees C library and are
      currently unique to G. antarctica. Gene expression analysis using RT-qPCR
      revealed two of the unknown genes to be up-regulated at -12  degrees C compared
      to 0  degrees C and 15  degrees C. These findings further contribute to the
      collective knowledge into G. antarctica cold adaptation and as a resource for
      understanding the ecological and physiological tolerance of psychrophilic
      microbes in general.

PMID- 29598998
TI  - World Health Organisation Classification of Lymphoid Tumours in Veterinary and
      Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61
      Cats.
AB  - To diagnose and classify the various entities of lymphomas, the World Health
      Organisation (WHO) classification is applied in human as well as in veterinary
      medicine. We validated the concordance of these classification systems by having
      a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from
      61 cats. In 59% of all cases, there was a match between their respective
      diagnoses of the lymphoma subtype. A complete consensus between the two
      evaluators was obtained for all samples with a diagnosis of diffuse large B-cell
      lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone
      lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also
      made in the majority of samples with enteropathy associated T-cell lymphoma
      (EATL) type II, although this subtype in cats has similarities to the 'indolent T
      cell lymphoproliferative disorder of the gastrointestinal tract', a provisional
      entity newly added to the revised human WHO classification in 2016. Very little
      consensus has been found with cases of EATL type I due to the fact that most did
      not meet all of the criteria of human EATL I. Hence, the human pathologist
      assigned them to the heterogeneous group of peripheral T-cell lymphomas (not
      otherwise specified). Consequently, concrete guidelines and advanced
      immunophenotyping based on the model of human medicine are essential to
      differentiate these challenging entities in veterinary medicine.

PMID- 29598999
TI  - Pulmonary Basaloid Squamous Cell Carcinoma in a Dog.
AB  - A 9-year-old neutered male crossbred dog with a 4-week history of progressive
      vestibulocerebellar signs was presented for necropsy examination. Gross
      examination revealed neoplastic growth in the lungs, thoracic lymph nodes, left
      kidney and cerebellum. Microscopically, the tumour consisted of an infiltrative,
      densely cellular, basaloid epithelial neoplastic growth with extensive areas of
      abrupt keratinization. Immunohistochemically, neoplastic cells expressed p63 and
      partially expressed cytokeratins 5/6. Based on these findings, the tumour was
      diagnosed as a primary pulmonary basaloid squamous cell carcinoma (BSSC) with
      metastasis to regional lymph nodes, kidney and brain. As far as the authors are
      aware, this is the first description of BSCC in an animal species.

PMID- 29599000
TI  - Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis).
AB  - Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis),
      held in two different institutions, are described. A cerebral glioblastoma was
      diagnosed based on histological and immunohistochemical findings in one of the
      animals following initial presentation with bilateral mydriasis, absent pupillary
      reflex, head tilt and ataxia. A second animal was humanely destroyed due to
      impaired locomotion associated with spondylosis and a post-mortem diagnosis of
      cholangiocarcinoma was made based on histology with further confirmation with
      immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from
      dental disease was diagnosed with an oral squamous cell carcinoma following an
      excisional biopsy from a non-healing wound in the lip. Due to progression of the
      neoplasia the animal was humanely destroyed and post-mortem examination revealed
      the presence on an additional unilateral phaeochromocytoma.

PMID- 29599001
TI  - Parotid Salivary Gland Basal Cell Adenocarcinoma in a Big-eared Opossum
      (Didelphis aurita).
AB  - The opossum (family Didelphidae) is a marsupial endemic to the Americas. Apart
      from the South American short-tailed opossum (Monodelphis domestica) and the
      Virginia opossum (Didelphis virginiana), there is considerable lack of knowledge
      about the health and diseases of most opossum species. Among these, the big-eared
      opossum (Didelphis aurita) is found in Argentina, Brazil and Paraguay. Natural
      and experimental studies have shown this species to be susceptible to infectious
      agents with zoonotic potential and the animals may play a role in transmission of
      such agents. However, neoplasia appears to be uncommon in this species. We
      describe the gross, microscopical and immunohistochemical features of a parotid
      salivary gland basal cell adenocarcinoma in a free-living big-eared opossum. This
      case represents the first report of salivary gland neoplasia in opossums.

PMID- 29599002
TI  - Amyloid-producing Odontoameloblastoma in a Black-tailed Prairie Dog (Cynomys
      ludovicianus).
AB  - A 6-year-old female black-tailed prairie dog (Cynomys ludovicianus) was presented
      with a space-occupying lesion in the left submandibular region. On computed
      tomography, a low attenuating, poorly circumscribed mass infiltrated the left
      mandibular bone, with osteolytic change. Microscopically, the lesion was composed
      of odontogenic epithelium proliferating in nests and embedded in abundant dental
      papilla-like ectomesenchyme, including dentine and enamel. Multifocal amyloid
      deposition was observed. Immunohistochemically, the neoplastic epithelial cells
      were positive for cytokeratin (CK) AE1/AE3, CK14 and p63. Some epithelial cells
      were positive for amelogenin and some adjacent to the amyloid deposits co
      expressed S100. The ectomesenchymal cells expressed vimentin and strong S100
      immunoreactivity was observed in odontoblast-like cells. The amyloid was
      immunolabelled with amelogenin. The tumour was diagnosed as amyloid-producing
      odontoameloblastoma.

PMID- 29599003
TI  - Ovarian Teratocarcinoma in an Emu (Dromaius novaehollandiae): Histopathological
      and Immunohistochemical Characterization.
AB  - A 17-year-old female emu (Dromaius novaehollandiae) was presented for clinical
      evaluation due to a 3-week history of anorexia and progressive weight loss. The
      emu died after sedation. At necropsy examination, the ovary and the majority of
      the oviduct were effaced by a multinodular cystic mass and accompanied by 6 l of
      coelomic effusion. Histopathology revealed a neoplasm composed of well
      differentiated, poorly organized tissues derived from ectoderm, mesoderm and
      endoderm. Tissues within the neoplasm expressed glial fibrillary acidic protein,
      desmin and cytokeratins AE1/AE3, respectively, confirming the diagnosis of
      teratocarcinoma.

PMID- 29599004
TI  - Pathology and Distribution of Velogenic Viscerotropic Newcastle Disease Virus in
      the Reproductive System of Vaccinated and Unvaccinated Laying Hens (Gallus gallus
      domesticus) by Immunohistochemical Labelling.
AB  - This study investigated the pathological changes in the reproductive system of
      laying hens that lead to the poor egg production and quality in Newcastle disease
      (ND) and the distribution of the virus in the system. Two hundred and forty Isa
      Brown pullets were divided randomly into vaccinated and unvaccinated groups (n =
      120 each). The vaccinated group was given Hitchner B1 vaccine at 1 day of age, La
      Sota vaccine at 4 weeks of age and Komarov vaccine at 9 and 16 weeks of age. At
      the peak of egg production, the laying hens (32 weeks old) were assigned randomly
      into four groups (n = 60): VC, vaccinated with ND vaccines and inoculated
      intramuscularly with velogenic viscerotropic ND virus (vvNDV); VU, vaccinated
      unchallenged; UC, unvaccinated challenged; and UU, unvaccinated unchallenged. UC
      hens showed depression, diarrhoea and later torticollis. Mortality in UC hens was
      90%. VC hens showed mild anorexia. The body weights of the UC hens were
      significantly (P <0.05) lower than those of UU hens. VC and UC hens showed a
      significant (P <0.05) drop in egg production. Only UC hens produced abnormal eggs
      and initially had swollen, oedematous, hyperaemic oviducts followed by atrophy
      and shortening of the reproductive tract with atresia of the ovarian follicles.
      The histopathological changes were of necrosis of the epithelium and secretory
      glands. VC hens showed mild inflammatory changes in the oviduct.
      Immunohistochemical labelling showed extensive presence of the virus in the
      ovary, infundibulum, magnum, isthmus, uterus and vagina of UC hens and in the
      ovary of VC hens. These changes will be the cause of serious egg production
      problems, especially in vaccinated layers in countries where vvNDV is enzootic.

PMID- 29599005
TI  - Inflammatory Lesion Patterns in Target Organs of Visna/Maedi in Sheep and their
      Significance in the Pathogenesis and Diagnosis of the Infection.
AB  - Ovine visna/maedi (VM) infection is characterized by the development of chronic
      inflammatory lesions in different organs, mainly in the lung, mammary gland and
      central nervous system (CNS), with either histiocytic or lymphocytic pattern
      predominance being described in the CNS. To help to understand the role of host
      immune response in the development of these patterns, 50 naturally-infected sheep
      and eight non-infected sheep from intensive milk-producing flocks were studied.
      The histological lesion patterns in the three main target organs in each sheep
      were characterized. Lesion severity was determined, including minimal lesions. A
      histiocytic pattern was observed in 23 sheep (46%), a lymphocytic inflammatory
      pattern in 19 sheep (38%) and a mixed inflammatory pattern in eight sheep (16%).
      Forty animals showed moderate or severe lesions (80%), while 10 had minimal
      lesions (20%). Moderate or severe lesions affected only one target organ in 20
      sheep (50%), two organs in 14 sheep (35%) and all three target organs in six
      sheep (15%). Infection was confirmed by immunohistochemistry (IHC) using an
      antibody specific for p28 of VM virus/caprine arthritis and encephalitis virus
      and by polymerase chain reaction (PCR) in all sheep. Minimal inflammatory lesions
      associated with positive IHC and PCR were observed. The results suggest that the
      development of a predominant inflammatory pattern in different organs within the
      same animal may be related to the host immune response. Minimal and focal
      lesions, not considered previously, should be taken into account when formulating
      a differential diagnosis in affected sheep.

PMID- 29599006
TI  - [Association between burnout syndrome and anxiety in residents and
      anesthesiologists of the Federal District].
AB  - BACKGROUND AND OBJECTIVE: There is a shortage of studies addressing the
      association between burnout syndrome and anxiety among anesthesiologists.
      Identifying the relationship between these two conditions is of fundamental
      importance for the prevention, follow-up, and treatment of the professionals.
      Thus, we evaluated the association between burnout syndrome and anxiety in
      anesthesiologists and residents of anesthesiology in the Federal District.
      METHOD: A cross-sectional study using a convenience sample of residents and
      anesthesiologists from the Federal District. The correlation between State Trait
      Anxiety Inventory and Burnout Syndrome (Maslach Burnout Inventory) was tested
      using multiple linear regression analysis, considering a significance level of
      5%. RESULTS: Of the 78 completed forms, there were predominance of males
      (57.69%), mean age of 42 +/- 9.7 years for anesthesiologists and 30 +/- 2.9 years
      for residents. Burnout syndrome had a prevalence of 2.43% among anesthesiologists
      and 2.70% among resident physicians, while a high risk for its manifestation was
      21.95% in anesthesiologists and 29.72% in resident physicians. There was a
      correlation between state-anxiety and the variables burnout emotional exhaustion,
      burnout depersonalization, and trait-anxiety. Regarding trait-anxiety, there was
      no statistically significant correlation with other variables. CONCLUSIONS: There
      is association between state-anxiety and the emotional exhaustion dimensions of
      burnout, burnout depersonalization, and trait-anxiety. The occurrence of anxiety
      can negatively influence the way the individual faces daily stressors, which may
      be related to the use of ineffective strategies to cope with stress.

PMID- 29599007
TI  - Radiation Dose Reduction at Low Tube Voltage CCTA Based on the CNR Index.
AB  - RATIONALE AND OBJECTIVES: We compared the radiation dose and diagnostic accuracy
      on 120- and 100-kVp coronary computed tomography angiography (CCTA) scans whose
      contrast-to-noise ratio (CNR) was the same. MATERIALS AND METHODS: We studied
      1311 coronary artery segments from 100 patients. For 120-kVp scans, the targeted
      image level was set at 25 Hounsfield units (HU). For 100-kVp scans, the targeted
      noise level was set at 30 HU to obtain the same CNR as at 120 kVp. We compared
      the CNR and the radiation dose on scans acquired at 120 and 100 kVp. Invasive
      coronary angiography (ICA) images were evaluated by an interventional coronary
      angiography specialist, and CCTA images were evaluated by a radiologist. Coronary
      artery disease was defined as a luminal narrowing ?50% for ICA and CCTA. With ICA
      considered the gold standard, the diagnostic accuracy (sensitivity, specificity,
      positive predictive value, and negative predictive value) was analyzed on both
      120- and 100-kVp CCTA images. We also compared the diagnostic accuracy for area
      under the receiver operating characteristic curve of the ICA and CCTA performed
      at 120 and 100 kVp. Two blinded observers visually evaluated the septal branch.
      RESULTS: The mean dose-length product was 48% lower at 100 kVp than at 120 kVp (P
      < .01). Under the 120-kVp CCTA protocol, the area under the curve, 95% confidence
      interval, sensitivity, specificity, positive predictive value, and negative
      predictive value were 0.94%, 0.91%-0.96%, 94.0%, 93.0%, 82.3%, and 98.1%,
      respectively; at 100 kVp these values were 0.94%, 0.92%-0.97%, 96.1%, 92.0%,
      85.2%, and 98.0%, respectively. Area under the receiver operating characteristic
      curve analysis revealed no significant difference in diagnostic accuracy between
      the two protocols (P = .87). CONCLUSIONS: At the same CNR, the 100-kVp CCTA
      protocol may help to reduce the radiation dose by approximately 50% compared to
      the 120-kVp protocol without degradation of diagnostic accuracy.

PMID- 29599008
TI  - Subspecialist Reader Reinterpretation of Referred Imaging Studies: Added Value
      and Justification.

PMID- 29599009
TI  - Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis
      in Head and Neck Squamous Cell Carcinoma.
AB  - RATIONALE AND OBJECTIVES: We aimed to investigate the incremental prognostic
      value of apparent diffusion coefficient (ADC) histogram analysis in patients with
      head and neck squamous cell carcinoma (HNSCC) and integrate it into a
      multivariate prognostic model. MATERIALS AND METHODS: A retrospective review of
      magnetic resonance imaging findings was conducted in patients with pathologically
      confirmed HNSCC between June 2012 and December 2015. For each tumor, six
      histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC
      (ADC10, ADC50, and ADC90); mean ADC values (ADCmean); kurtosis; and skewness. The
      clinical variables included age, sex, smoking status, tumor volume, and tumor
      node metastasis stage. The association of these histogram and clinical variables
      with overall survival (OS) was determined. Further validation of the histogram
      parameters as independent biomarkers was performed using multivariate Cox
      proportional hazard models combined with clinical variables, which was compared
      to the clinical model. Models were assessed with C index and receiver operating
      characteristic curve analyses for the 12- and 36-month OS. RESULTS: Ninety-six
      patients were eligible for analysis. Median follow-up was 877 days (range, 54
      1516 days). A total of 29 patients died during follow-up (30%). Patients with
      higher ADC values (ADC10 > 0.958 * 10-3 mm2/s, ADC50 > 1.089 * 10-3 mm2/s, ADC90
      > 1.152 * 10-3 mm2/s, ADCmean > 1.047 * 10-3 mm2/s) and lower kurtosis (<=0.967)
      were significant predictors of poor OS (P < .100 for all). After adjusting for
      sex and tumor node metastasis stage, the ADC90 and kurtosis are both significant
      predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004)
      and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC
      parameters into the clinical model, the C index and diagnostic accuracies for the
      12- and 36-month OS showed significant improvement. CONCLUSIONS: ADC histogram
      analysis has incremental prognostic value in patients with HNSCC and increases
      the performance of a multivariable prognostic model in addition to clinical
      variables.

PMID- 29599010
TI  - Toward Augmented Radiologists: Changes in Radiology Education in the Era of
      Machine Learning and Artificial Intelligence.
AB  - Radiology practice will be altered by the coming of artificial intelligence, and
      the process of learning in radiology will be similarly affected. In the short
      term, radiologists will need to understand the first wave of artificially
      intelligent tools, how they can help them improve their practice, and be able to
      effectively supervise their use. Radiology training programs will need to develop
      curricula to help trainees acquire the knowledge to carry out this new
      supervisory duty of radiologists. In the longer term, artificially intelligent
      software assistants could have a transformative effect on the training of
      residents and fellows, and offer new opportunities to bring learning into the
      ongoing practice of attending radiologists.

PMID- 29599011
TI  - Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and
      experience in Hong Kong.
AB  - AIM: The study aims to analyze the incidence, clinical features, investigation
      findings and treatment outcomes of anti-N-methyl-d-aspartate receptor
      encephalitis in children from Hong Kong. METHOD: A retrospective study was
      carried out on paediatric patients diagnosed with anti-NMDAR encephalitis in Hong
      Kong from January 2009 to December 2015. RESULTS: Fifteen patients (67% female,
      93% Chinese) were identified over seven years and the estimated incidence in Hong
      Kong was 2.2/million children per year (95% CI 1.2-3.6). The median age of
      presentation was 12 years (range 1-17 years). The most common symptom groups
      observed were abnormal psychiatric behavior or cognitive dysfunction (14/15, 93%)
      and seizures (14/15, 93%), followed by speech dysfunction (13/15, 87%), movement
      disorders (12/15, 80%), decreased level of consciousness (10/15, 67%) and
      autonomic dysfunction or central hypoventilation (5/15, 33%). The median number
      of symptom groups developed in each patient was 5 (range 3-6). All patients were
      treated with intravenous immunoglobulin and/or steroids. Three patients (20%)
      with more severe presentation required additional plasmapheresis and rituximab.
      Outcome was assessable in 14 patients. Among those eleven patients who had only
      received intravenous immunoglobulin and/or steroids, nine patients (82%) achieved
      full recovery. One patient (9%) had residual behavioral problem, while another
      one (9%) who developed anti-NMDAR encephalitis after herpes simplex virus
      encephalitis was complicated with dyskinetic cerebral palsy and epilepsy. Among
      those three patients who required plasmapheresis and rituximab, one (33%) had
      full recovery and two (66%) had substantial recovery. The median duration of
      follow up was 20.5 months (range 3-84 months). CONCLUSION: Anti-NMDAR
      encephalitis is an acquired, severe, but potentially treatable disorder.
      Ethnicity may play a role in the incidence of anti-NMDAR encephalitis and we have
      provided a local incidence with the majority of patients being Chinese. The
      diagnosis of anti-NMDAR encephalitis should be considered in children presenting
      with a constellation of symptoms including psychiatric and neurological
      manifestations. Patients may respond to first line immunotherapy. For those who
      do not, second line therapy is indicated in order to achieve a better outcome.

PMID- 29599012
TI  - Metaorganisms in extreme environments: do microbes play a role in organismal
      adaptation?
AB  - From protists to humans, all animals and plants are inhabited by microbial
      organisms. There is an increasing appreciation that these resident microbes
      influence the fitness of their plant and animal hosts, ultimately forming a
      metaorganism consisting of a uni- or multicellular host and a community of
      associated microorganisms. Research on host-microbe interactions has become an
      emerging cross-disciplinary field. In both vertebrates and invertebrates a
      complex microbiome confers immunological, metabolic and behavioural benefits;
      conversely, its disturbance can contribute to the development of disease states.
      However, the molecular and cellular mechanisms controlling the interactions
      within a metaorganism are poorly understood and many key interactions between the
      associated organisms remain unknown. In this perspective article, we outline some
      of the issues in interspecies interactions and in particular address the question
      of how metaorganisms react and adapt to inputs from extreme environments such as
      deserts, the intertidal zone, oligothrophic seas, and hydrothermal vents.

PMID- 29599013
TI  - An allometric analysis of sexual dimorphism in Ctenomys australis: integrating
      classic morphometry and functional performance in vivo.
AB  - The South American rodents of the genus Ctenomys (Rodentia, Hystricognathi),
      which use both forelimbs and incisors to dig, show strong, specialized
      morphological adaptations to living in the underground niche. In these rodents,
      the effectiveness of a bite - in this case the potential to inflict physical
      damage - mostly depends on the strength of the incisors (e.g. bending and torsion
      stresses) and the power of the masseteric muscle of the jaw. Ctenomys australis
      (the sand dune tuco-tuco) is a highly territorial subterranean rodent that builds
      large and exclusive burrow systems in coastal sand dunes found continuously along
      the Atlantic coast of the Buenos Aires province, Argentina. Incisors in this
      species are used both in agonistic encounters among congeners (i.e. reproductive
      or territorial intentions) as well as to dig and increase the size of their
      burrows daily (e.g. acquisition of plant material as food resources). We first
      characterized sexual dimorphism in cranial traits involved in aggressive
      interactions between males, analyzing ontogenetic trajectories of both sexes. We
      also analyzed some remarkable attributes of sexual dimorphism in subadult and
      adult individuals, the bending and torsion stresses and the bite performance in
      vivo, hypothesizing that males are able to apply comparatively stronger bite
      forces at their incisor tips than females, concordant with a broader mandible for
      the insertion of a powerful adductor musculature. Bite forces were measured in
      vivo in wild animals of both sexes using a strain gauge load cell force
      transducer. These individuals were also used to estimate the incisor area (CA),
      the 2nd moment of inertia of the incisors (I, or the bending strength to external
      forces), and the torsional strength of the incisor (J), all traits involved in
      the production of the force that can be withstood at the incisor tips. Ontogeny
      explained some sexual differences in the cranial traits of adults, expressed as
      (i) morphological changes related to body size variation, and (ii) morphological
      changes associated with differences in the slope of ontogenetic trajectories
      (regardless of body size variation). Recordings of in vivo bite forces were
      significantly higher in adult males than in females. These differences in bite
      forces were not associated with the sex itself, but the sexual dimorphism in body
      size. Although males did not show significantly higher allometric coefficients
      for I, J and CA than females, males still showed a strong sexual dimorphism in
      these traits due to body size variation. On the other hand, measurements of
      mandibular width - an estimator of the relative size of masseteric muscles - in
      vivo showed strong differences between sexes, suggesting higher force performance
      at the incisor tips for males. Overall, we observed that many attributes related
      to bite performance might have been molded by sexual selection, which implies
      differences in allometric coefficients from some morphological traits throughout
      ontogeny.

PMID- 29599015
TI  - Letters.

PMID- 29599014
TI  - 2017 Hypertension guidelines: New opportunities and challenges.

PMID- 29599016
TI  - Authors' response.

PMID- 29599017
TI  - Opioid prescribing practices from 2010 through 2015 among dentists in the United
      States: What do claims data tell us?
AB  - BACKGROUND: Dentists wrote 6.4% of all opioid prescriptions in the United States
      in 2012. The purpose of this study was to examine opioid prescription rates,
      dosage of opioids prescribed, type of opioid drug prescribed, and type of dental
      visit at which dentists prescribe opioids. METHODS: The authors used the 2010
      through 2015 Truven Health Marketscan Research databases and the Prescription
      Drug Monitoring Program (PDMP) Training and Technical Assistance Center
      conversion data set. The authors conducted descriptive analyses for days' supply,
      quantity prescribed, and daily morphine milligram equivalent dose. RESULTS: The
      opioid prescription rate per 1,000 dental patients increased from 130.58 in 2010
      to 147.44 in 2015. Approximately 68.41% of all opioids prescribed were during
      surgical dental visits and approximately 31.10% during nonsurgical dental visits.
      During nonsurgical dental visits at which dentists prescribed an opioid, most of
      the procedures were restorative. CONCLUSIONS: Among a population of dental
      patients with private insurance, opioid prescribing rates in the United States
      increased slightly from 2010 to 2015. The largest increase was among 11- through
      18-year-olds. Almost one-third of opioid prescriptions written by dentists were
      associated with nonsurgical dental visits. PRACTICAL IMPLICATIONS: Use of PDMP
      resources and use of nonopioid analgesics could help reduce the number of opioid
      prescriptions in dentistry.

PMID- 29599018
TI  - Sex and race or ethnicity disparities in opioid prescriptions for dental
      diagnoses among patients receiving Medicaid.
AB  - BACKGROUND: The objective of this study was to identify specific factors (sex,
      race or ethnicity, and health care provider type) associated with patient receipt
      of an opioid prescription after a dental diagnosis. METHODS: The authors used
      Medicaid claims dated from January 1, 2013, through September 30, 2015, for 13 US
      states in this study. The authors identified oral health-related conditions by
      using International Classification of Diseases, Ninth Revision, Clinical
      Modification diagnosis codes 520.0 through 529.9. RESULTS: During the 2013-2015
      study period, among the more than 890,000 Medicaid patients with a dental
      diagnosis, 23% received an opioid within 14 days of diagnosis. Female patients
      were 50% more likely to receive an opioid for pain management of a dental
      condition than were men (odds ratio [OR], 1.53; 95% confidence interval [CI],
      1.52 to 1.55). Non-Hispanic whites and African Americans were approximately twice
      as likely to receive opioids than were Hispanics (OR, 2.11; 95% CI, 2.05 to 2.17
      and OR, 1.88; 95% CI, 1.83 to 1.93, respectively). Patients receiving oral health
      care in an emergency department were nearly 5 times more likely to receive an
      opioid prescription than were patients treated in a dental office (OR, 4.66; 95%
      CI, 4.59 to 4.74). Patients with a dental condition diagnosed were nearly 3 times
      as likely to receive an opioid from a nurse practitioner as from a dentist (OR,
      2.64; 95% CI, 2.57 to 2.70). Opioid use was substantially higher among African
      American female patients (OR, 3.29; 95% CI, 3.18 to 3.40) and non-Hispanic white
      female patients (OR, 3.24; 95% CI, 3.14 to 3.35) than among Hispanic female
      patients. CONCLUSIONS: Opioid prescribing patterns differ depending on patient
      race or ethnicity, sex, and health care provider source in patients with a dental
      diagnosis in the United States. PRACTICAL IMPLICATIONS: Dentists are providing
      substantially less opioid prescriptions compared to their medical colleagues for
      pain treatment following a dental diagnosis in the Medicaid population. When
      considering pain management for dental and related conditions, dentists should
      continue with conservative prescribing practices as recommended.

PMID- 29599019
TI  - Benefits and harms associated with analgesic medications used in the management
      of acute dental pain: An overview of systematic reviews.
AB  - BACKGROUND: Effective pain management is a priority in dental practice.
      Government and private agencies highlight the need to provide optimal pain
      relief, balancing potential benefits and harms of both opioid and nonopioid
      analgesic agents. The purpose of this study is to summarize the available
      evidence on the benefits and harms of analgesic agents, focusing on preexisting
      systematic reviews. TYPES OF STUDIES REVIEWED: An overview of systematic reviews
      was conducted to evaluate the efficacy or reported adverse events associated with
      orally administered medication or medication combinations for relief of acute
      pain. Reviews were inclusive of all age populations but were limited to those
      that evaluated medication and medication combinations marketed in the United
      States and had moderate or high methodological quality according to the A
      MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool. RESULTS: Five
      reviews were found eligible for inclusion. The data identified combinations of
      ibuprofen and acetaminophen as having the highest association with treatment
      benefit in adult patients and the highest proportion of adult patients who
      experienced maximum pain relief. Diflunisal, acetaminophen, and oxycodone were
      found to have the longest duration of action in adult patients. Medication and
      medication combinations that included opioids were among those associated most
      frequently with acute adverse events in both child and adult-aged patient
      populations. PRACTICAL IMPLICATIONS: The best available data suggested that the
      use of nonsteroidal medications, with or without acetaminophen, offered the most
      favorable balance between benefits and harms, optimizing efficacy while
      minimizing acute adverse events.

PMID- 29599020
TI  - The prescription monitoring program data: What it can tell you.

PMID- 29599021
TI  - Quality measures everywhere: The case for parsimony.

PMID- 29599022
TI  - A robust periodic capacitated arc routing problem for urban waste collection
      considering drivers and crew's working time.
AB  - In this paper, a novel mathematical model is developed for robust periodic
      capacitated arc routing problem (PCARP) considering multiple trips and drivers
      and crew's working time to study the uncertain nature of demand parameter. The
      objective function of the proposed model aims to minimize total traversed
      distance and total usage cost of vehicles over a planning period. To solve the
      problem, an improved hybrid simulated annealing algorithm (SA) is developed based
      on a heuristic algorithm and an efficient cooling equation. It has been proved
      that the performance of the proposed algorithm is acceptable in comparison with
      the exact solution method. Finally, the results have shown the effects of
      different uncertainty level of the demand parameter on the problem to be
      considered as a managerial overview in decision making process under uncertainty.

PMID- 29599023
TI  - Comparative environmental and human health evaluations of thermolysis and
      solvolysis recycling technologies of carbon fiber reinforced polymer waste.
AB  - This quantitative research aims to compare environmental and human health impacts
      associated with two recycling technologies of CFRP waste. The 'baseline'
      recycling technology is the conventional thermolysis process via pyrolysis and
      the 'alternative' recycling technology is an emerging chemical treatment via
      solvolysis using supercritical water (SCW) to digest the thermoset matrix. Two
      Gate-to-Gate recycling models are developed using GaBi LCA platform. The selected
      functional unit (FU) is 1 kg CFRP waste and the geographical boundary of this
      comparative LCIA is defined to be within the U.S. The results of this comparative
      assessment brought to light new insights about the environmental and human health
      impacts of CFRP waste recycling via solvolysis using SCW and, therefore, helped
      close a gap in the current state of knowledge about sustainability of SCW-based
      solvolysis as compared to pyrolysis. Two research questions are posed to identify
      whether solvolysis recycling offers more environmental and human health gains
      relative to the conventional pyrolysis recycling. These research questions lay
      the basis for formulating two null hypotheses (H0,1 and H0,2) and their
      associated research hypotheses (H1,1 and H1,2). LCIA results interpretation
      included 'base case' scenarios, 'sensitivity studies,' and 'scenarios analysis.'
      The results revealed that: (a) recycling via solvolysis using SCW exhibits no
      gains in environmental and human health impacts relative to those impacts
      associated with recycling via pyrolysis and (b) use of natural gas in lieu of
      electricity for pyrolyzer's heating reduces the environmental and human health
      impacts by 37% (lowest) and up to 95.7% (highest). It is recommended that on
      going experimental efforts that focus only on identifying the best solvent for
      solvolysis-based recycling should also consider quantification of the energy
      intensity as well as environmental and human health impacts of the proposed
      solvents.

PMID- 29599024
TI  - Plastic recycling in the Nordics: A value chain market analysis.
AB  - There is low utilisation of plastic waste in the Nordic region and only a
      fraction of plastic materials go back into production processes through reuse and
      recycling practices. This paper aims to increase knowledge concerning factors
      that inhibit demand for recycled plastics, and to identify critical barriers for
      plastic recycling across the regional plastics value chain. A literature review
      and targeted interviews with key actors across the plastics value chain enabled
      the mapping of interactions between the major actors and identified hotspots that
      act as barriers to the flow of plastic materials. Barriers identified include the
      lack of both supply and demand of recycled plastic and are mainly attributed to
      the fragmented market of secondary materials. The main hotspots identified are
      the low demand due to price considerations, insufficient traceability and
      transparency in value chain transactions, and general design deficiencies in the
      recyclability of products. Value chain coordination is considered as the most
      important intervention by the interviewees, followed by the need for increased
      investment in innovation and technology development. Complementary measures that
      could counteract the identified barriers include public procurement for resource
      efficiency, ban on the incineration of recyclable materials, and specifications
      on the design of plastic products for reducing the number of different polymers,
      and the number and usage of additives.

PMID- 29599025
TI  - The type of approach does not influence TKA component position in revision total
      knee arthroplasty - A clinical study using 3D-CT.
AB  - BACKGROUND: The influence of the surgical approach on the position of the
      prosthetic components in revision of total knee arthroplasties (rTKA) is still
      not clear. This study compared the medial parapatellar approach (MPA) and lateral
      parapatellar subvastus approach with tibial tubercle osteotomy (LPA). METHODS:
      Forty-two consecutive patients underwent rTKA from 2006 to 2016 with either MPA
      (n=21) or LPA (n=21) because of aseptic loosening, infection, malposition or
      instability (mean follow-up: 41.5months). Revision TKA component position and leg
      alignment were assessed on three-dimensional CT (3D-CT) images and compared
      between groups using a t-test (p<0.05). Rotation of rTKA components graded into
      internal, neutral or external rotation and rates of postoperative complications
      and revisions were compared between groups with a chi2-test (p<0.05). RESULTS:
      Group MPA and LPA showed no significant differences with respect to the femoral
      component (coronal: 0.6 degrees  vs 0.9 degrees ; sagittal: 7.5 degrees  vs 7.7
      degrees ; transversal: 0.4 degrees  vs -0.2 degrees ), tibial component (coronal:
      0.1 degrees  vs 0.3 degrees ; sagittal: 3.1 degrees  vs 1.6 degrees ;
      transversal: 6.9 degrees  vs 9.3 degrees ) and leg alignment (varus: 0.2 degrees 
      vs 1.1 degrees ) (p<0.05). Group LPA showed a non-significant (p=0.25) higher
      incidence of neutrally (28.6% vs 9.5%) and less internally (23.8% vs 38.1%)
      rotated tibial components. Rates of complication and revisions did not differ
      significantly. CONCLUSIONS: In contrast with primary TKA, the two approaches did
      not influence postoperative rTKA position. This can be explained with the more
      extensive approach at rTKA and means that no corrections of the orientation of
      the components are needed performing either MPA or LPA.

PMID- 29599027
TI  - Predictors of the effect of bariatric surgery on knee osteoarthritis pain.
AB  - INTRODUCTION: Bariatric surgery reduces obesity and knee osteoarthritis (OA)
      pain, but some patients improve more than others. We aimed to identify
      characteristics that predict this knee pain improvement. METHODS: We reviewed NYU
      Langone Health bariatrics records (2002-2015) and called eligible patients
      reporting pre-operative knee pain. Patients were asked to rate their pain on a 10
      point scale at three time points: before surgery, one year post-surgery, and time
      of survey administration. Subjects were asked about pre-operative knee injuries
      and surgeries, presence of OA in other joints, and OA family history. Data were
      analyzed using paired t-tests and ANOVA. RESULTS: Of 125 eligible patients
      reporting knee pain, we analyzed the 120 patients who had laparoscopic gastric
      band (LAGB) surgery. The cohort was 78.3% female, with an average age at surgery
      of 49.7 +/- 10.2 years. There was no correlation between pre-operative body mass
      index (BMI) and knee pain reduction at one year post-LAGB, but the subgroup with
      the most BMI improvement reported the most knee improvement (p = 0.043). We found
      significantly better pain reduction after one year in younger patients (p =
      0.009). Those with prior knee injuries improved less than those who were injury
      free (p = 0.044), but a history of prior knee surgery was not similarly
      significant. Patients with multifocal OA improved less (p = 0.001). CONCLUSION:
      Younger knee OA patients and those without prior knee injury or other OA
      involvement, experience more knee pain relief from LAGB weight loss surgery. LAGB
      may be a viable treatment option for knee OA pain, irrespective of the degree of
      obesity.

PMID- 29599029
TI  - Enhanced immune responses by co-adsorption of liposomal adjuvant formulations to
      the aluminum-antigen complex.

PMID- 29599028
TI  - Phenotypic characterization of patients with rheumatologic manifestations of
      common variable immunodeficiency.
AB  - : Patients with common variable immunodeficiency (CVID) have a higher incidence
      of rheumatologic disorders. To delineate this clinical association, we
      investigated the phenotypic features of patients with CVID affected by these
      conditions. METHODS: We conducted a retrospective analysis of 870 pediatric and
      adult patients with CVID included in the United States Immunodeficiency Network
      (USIDNET) registry. Outcomes included clinical characteristics (age, gender,
      ethnicity, rheumatologic diagnosis, and comorbidities), infectious history and
      basic immunophenotype (serum immunoglobulin levels, CD19+ B cells, and CD4/CD8
      ratio) in patients with CVID and rheumatologic disorders compared to those with
      non-inflammatory CVID. Demographic and clinical data were compared using chi
      square, Fisher's exact or Wilcoxon-Mann-Whitney tests. Non-parametric tests,
      single and multiple logistic regression models were used to evaluate the
      relationship between CVID-associated rheumatologic disorders and basic
      immunophenotypic parameters (IgA, IgM, CD19+ B-cell counts, and CD4/CD8 ratios).
      RESULTS: Physician-reported rheumatic diseases were present in 5.9% of patients
      with CVID (n = 51) included in the registry. Although CVID affects both sexes
      equally, and patients are of predominantly White-Caucasian ethnicity, there were
      more females (3.3:1 female to male ratio) and increased proportion of non-white
      patients in the rheumatologic disease group (p < 0.05). Specific disorders
      included: inflammatory arthritis (n = 18), Sjogren's syndrome (n = 11), SLE (n =
      8), Raynaud's syndrome (n = 8), vasculitis (n = 9), MCTD (n = 3), and other (n =
      5). In about one-third of patients, a rheumatologic condition was associated with
      an additional inflammatory complication or malignancy. In regards to the
      immunophenotype parameters compared (CD19+ B-cell counts, CD4/CD8 ratio, IgA, and
      IgM), no significant differences were demonstrated between the two groups.
      CONCLUSION: Our findings highlight the coexistence of primary antibody
      immunodeficiencies and systemic rheumatologic disorders, describe the spectrum of
      rheumatologic manifestations, and contrast differences in relevant demographic,
      clinical and immunophenotype parameters in the largest registry of CVID patients
      in the U.S. In spite of its limitations, our study details the intersection of
      systemic autoimmunity and CVID and provides valuable insights into these two
      groups of disorders. Further delineating the link between systemic autoimmunity
      and humoral immunodeficiencies can provide novel insights into the immune
      abnormalities underlying these related conditions.

PMID- 29599030
TI  - Pulmonary Hypertension in Central Australia: A Community-Based Cohort Study.
AB  - BACKGROUND: The burden of pulmonary hypertension (PHT) in Central Australia has
      not been previously studied. Our aim is to characterise the prevalence, clinical
      classification, and long-term survival of individuals with PHT in Central
      Australia. METHODS: A community-based cohort study of all individuals diagnosed
      with PHT in Central Australia between 2005 and 2016 was undertaken. We estimated
      PHT prevalence using population data, describe clinical PHT classification, and
      characterised long-term survival using Kaplan-Meier approaches. RESULTS: A total
      of 183 patients were identified (mean age 52+/-16years, 63% female). Of these
      individuals, 149 (81.4%) were of Aboriginal and Torres Strait Islander (ATSI)
      descent. The prevalence per 100,000 of any PHT was significantly higher In ATSI
      (723 [95% CI 608-839] compared to non-ATSI individuals (126 [95% CI 84-168],
      p<0.001). Furthermore, ATSI individuals were diagnosed at younger ages compared
      to non-ATSI individuals (49+/-15 vs 64+/-16years, p<0.001). Median estimated
      pulmonary artery systolic pressure (ePASP) was higher in patients with pulmonary
      arterial hypertension (PAH) compared to other causes (62 [IQR 54-69] vs 50 [IQR
      44-58] mmHg, p<0.01). The median survival rate from diagnosis was 9 years (IQR
      7.2-13.2). Age and ePASP were significant predictors of mortality (HR 1.05 [95%
      CI 1.02-1.07] and HR 1.56 [95% 1.00-2.42] respectively). CONCLUSIONS: In this
      community based study, we found a high burden of PHT in Central Australia. The
      prevalence of PHT is greater in ATSI individuals and is diagnosed at younger ages
      compared to non-ATSI individuals. Together with other cardiovascular diseases,
      PHT may be in-part contributing to the gap in life expectancy between ATSI and
      non-ATSI individuals.

PMID- 29599031
TI  - Response to Letter to the Editor on "Acetabular Revision Using Trabecular Metal
      Augments for Paprosky Type 3 Defects".

PMID- 29599032
TI  - Femoral Bone Restoration Patterns in Revision Total Hip Arthroplasty Using
      Distally Fixed Modular Tapered Titanium Stems and an Extended Trochanteric
      Osteotomy Approach.
AB  - BACKGROUND: Mechanical failure of modular revision stems is a serious
      complication in revision total hip arthroplasty. The lack of adequate osseous
      support to the proximal component, especially in cases of an extended
      trochanteric osteotomy approach, is considered a risk factor for stem failure. In
      this study, we analyze proximal bone regeneration patterns in patients undergoing
      revision total hip arthroplasty for aseptic stem loosening through an extended
      trochanteric osteotomy approach using an uncemented dual modular stem. METHODS:
      Fifty-four patients treated for aseptic stem loosening were radiologically
      reviewed. The femur was divided according to the Gruen zones. Preoperative bone
      loss, formation of new cancellous bone, and presence of direct osseous contact to
      the stem were noted right away for each Gruen zone. The presence of osseous
      support at the modular junction and the proximal component were examined.
      RESULTS: All patients showed restoration of proximal bone mass at final follow
      up. New bone formation was first seen in more distally located Gruen zones. Cases
      with longer proximal components had a trend toward earlier osseous support at the
      modular junction. Overall, 75% of patients showed osseous support at the modular
      junction 2 years after surgery. CONCLUSION: Restoration of proximal bone occurs
      in a distal to proximal direction. Shorter proximal components require more time
      until osseous support to the modular junction is achieved, which may result in a
      higher risk of mechanical failure. Based on this study, bony support at the
      modular junction should not be expected in 25% of cases 2 years after surgery.

PMID- 29599033
TI  - Periarticular Ropivacaine Cocktail Is Equivalent to Liposomal Bupivacaine
      Cocktail in Bilateral Total Knee Arthroplasty.
AB  - BACKGROUND: This study compares the effectiveness of 2 commonly used
      periarticular injection formulations: liposomal bupivacaine and bupivacaine (EXP)
      and ropivacaine, epinephrine, ketorolac, and clonidine (ROP) in patients
      undergoing bilateral total knee arthroplasty or unicompartmental knee
      arthroplasty. METHODS: Twenty-six total knee arthroplasty patients (52 knees) and
      3 unicompartmental knee arthroplasty patients (6 knees) undergoing simultaneous,
      bilateral arthroplasty were randomized to receive periarticular injections in a
      blinded fashion. Even birth year patients were selected for PAI of EXP in the
      right knee and ROP in the left knee. This was reversed for odd birth years.
      Visual analog scale pain scores for each knee and patient perceived difference in
      knee functional recovery were recorded during physical therapy, throughout the
      hospitalization. RESULTS: There was no difference in visual analog scale pain
      scores between the EXP and ROP injected knees at any time point during the first
      2 days after surgery. Postoperative pain scores averaged 41.9 mm (range 0-100 mm)
      for EXP and 43.1 mm (range 0-100 mm) for ROP. Patients were unable to detect a
      difference in the functional recovery between their knees on postoperative day 0,
      1, or 2. No complications as a result of either periarticular injection occurred.
      CONCLUSION: Periarticular injections of EXP and ROP are equally effective after
      knee arthroplasty and patients do not appreciate differences between knees as
      determined by pain score or perceived functional recovery during the first 2 days
      after bilateral knee arthroplasty. This study demonstrates that a liposomal
      bupivacaine injection does not add an incremental benefit for pain control
      compared to a less expensive injection formulation.

PMID- 29599034
TI  - Clinical Outcomes and Bearing-Specific Complications Following Fourth-Generation
      Alumina Ceramic-on-Ceramic Total Hip Arthroplasty: A Single-Surgeon Series of 749
      Hips at a Minimum of 5-Year Follow-Up.
AB  - BACKGROUND: The purpose of this study is to evaluate the minimum 5-year outcomes
      and bearing-specific complications in a single surgeon series of fourth
      generation alumina ceramic-on-ceramic total hip arthroplasties (THAs). METHODS:
      We retrospectively analyzed 667 patients (749 hips) who underwent primary THAs by
      a single surgeon using fourth-generation alumina ceramic bearings. There were 315
      men and 352 women with a mean age of 54.2 years. The surgeon used cementless
      prostheses with an identical design and BIOLOX Delta ceramics in all hips, using
      a 36-mm head in 472 hips (63%) and a 32-mm head in 227. The mean follow-up
      duration was 6.5 years (range, 5 to 8 years). RESULTS: The mean Harris hip score
      improved from 45.6 points preoperatively to 91.3 points at final follow-up. All
      but 1 acetabular cup and all femoral stems were well fixed. No radiographic
      evidence of osteolysis was identified at final follow-up. There were 2 (0.3%)
      ceramic liner fractures and no ceramic head fractures. A total of 48 hips (6.4%)
      exhibited audible noise (29 clickings and 19 squeakings), but no patient required
      revision. Other complications were 1 dislocation, 1 deep infection, 3 iliopsoas
      tendonitis, and 6 periprosthetic femoral fractures. Kaplan-Meier survivorship for
      revision for any reason was 98.6% (95% confidence interval, 97.7-99.5) at 6.5
      years. CONCLUSION: Delta ceramic-on-ceramic THAs had a high rate of survivorship
      without radiographic evidence of osteolysis at 6.5-year follow-up. However, we
      found 0.3% ceramic liner fractures and 6.4% audible noises associated with the
      use of Delta ceramics.

PMID- 29599035
TI  - What Is the Role of Diagnostic and Therapeutic Sonication in Periprosthetic Joint
      Infections?
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is one of the most dreaded
      complications in joint replacement surgery. Diagnosis and treatment can be
      difficult and biofilms are of major concern due to their low susceptibility
      toward antibiotics. METHODS: This review focuses on the use of sonication as an
      evolving diagnostic and adjunct treatment modality in the context of PJI.
      Therapeutic application of sonication is discussed separately for its (i) direct
      action on bacteria, (ii) synergistic effects with antibiotics, and (iii) effects
      on release of antibiotics from bone cement. RESULTS: Used as a diagnostic tool,
      sonication shows promising results with respect to sensitivity and specificity
      when compared to conventional methods, notably after previous administration of
      antibiotics. As an adjunct treatment modality, the chemical, physical, and
      mechanical effects of sonication are primarily driven by cavitation and
      recognized as the main cause for bactericidal effects but the exact underlying
      mechanisms have not been identified yet. Sonication alone does not have the
      ability to completely eradicate biofilms but synergistic effects when used in
      conjunction with antibiotics have been reported. There is also evidence for
      enhanced antibiotic release from bone cement. CONCLUSION: Sonication is as an
      evolving modality in the context of PJIs. As a diagnostic tool, it has not been
      introduced in routine clinical practice and sonication as a treatment modality in
      PJIs is still in an experimental stage. Factors such as frequency, pressure,
      chemical activity, intensity, and exposure time need to be evaluated for optimal
      application of sonication and may also improve study comparison.

PMID- 29599036
TI  - A Call to Upgrade Our Adult Reconstruction Fellowship Websites!

PMID- 29599037
TI  - Contact burns in the elderly: Do we need a campaign of prevention?

PMID- 29599038
TI  - Neer Award 2018: the effect of preoperative education on opioid consumption in
      patients undergoing arthroscopic rotator cuff repair: a prospective, randomized
      clinical trial.
AB  - BACKGROUND: Opioids are commonly administered for the treatment of acute and
      chronic pain symptoms. The current health care system is struggling to deal with
      increasing medication abuse and rising mortality rates from overdose.
      Preoperative patient-targeted education on opioid use is an avenue yet to be
      explored. The purpose of the study was to determine whether preoperative
      narcotics education reduces consumption after arthroscopic rotator cuff repair
      (ARCR). METHODS: Patients undergoing primary ARCR at our institution were
      randomized to receiving opioid-related preoperative education or not. Patients
      filled out preoperative questionnaires detailing complete medical history and
      visual analog scale (VAS) for pain. Patients completed questionnaires regarding
      their opioid consumption and pain at their 2-week, 6-week, and 3-month follow-up.
      RESULTS: The study enrolled 140 patients. Patients in the study group consumed
      significantly less narcotics than the control group at the 3-month follow-up.
      Patients in the education group were 2.2 times more likely to discontinue
      narcotic use by the end of follow-up (odds ratio, 2.19; P = .03). In addition,
      patients with a history of preoperative narcotic use that were in the education
      group were 6.8 times more likely to discontinue narcotics by the end of follow-up
      (odds ratio, 6.8; P = .008). DISCUSSION/CONCLUSIONS: The findings of this study
      determined that preoperative education intervention significantly decreased the
      number of narcotic pills consumed at 3 months after ARCR. In addition, education
      resulted in earlier cessation of opioids; therefore, directed patient education
      can help alleviate the current opioid epidemic.

PMID- 29599040
TI  - Volumetric locking free 3D finite element for modelling of anisotropic visco
      hyperelastic behaviour of anterior cruciate ligament.
AB  - Solids such as polymers, soft biological tissues display visco-hyperelastic,
      isochoric and finite deformation behaviour. The incompressibility constraint
      imposed severe restriction on the displacement field results in volumetric
      locking. Many techniques have been developed to address the issue such as reduced
      integration, mixed formulation, B-Bar and F-Bar methods, each of them with their
      own merits and demerits. In this work, we have developed a 3D finite element
      (hereby referred as J-Bar method) to counter volumetric locking in visco
      hyperelastic solids. To validate the proposed J-Bar method, rheological
      characteristics of the human anterior cruciate ligament (ACL) were predicted and
      compared with the experimental results.

PMID- 29599041
TI  - Between-day reliability of MyotonPRO for the non-invasive measurement of muscle
      material properties in the lower extremities of patients with a chronic spinal
      cord injury.
AB  - Measuring the muscle properties of patients with spinal cord injuries (SCIs) is
      important to better understand their biomechanical features. In this study, we
      sought to evaluate the between-day reliability of MyotonPRO, a handheld device
      that can measure muscle mechanical properties, and assess whether it is reliable
      to measure muscle properties over time in patients with SCI. Thirteen men with
      complete SCIs (age 53.9 +/- 6.3 years, height 171.0 +/- 5.2 cm, weight 66.1 +/-
      5.8 kg), and injury levels ranging from L1 to T12, were enrolled. Oscillation
      frequency; logarithmic decrement; dynamic stiffness; mechanical stress relaxation
      time; and creep of the biceps femoris, medial and lateral gastrocnemius, rectus
      femoris, tibialis anterior, and Achilles tendon were measured on consecutive days
      using MyotonPRO. The intraclass coefficient for most muscles and the Achilles
      tendon ranged from 0.53 to 0.99 for all parameters. The percentage standard error
      of the measurement for many parameters in most muscles and the Achilles tendon
      was less than 10%. Bland-Altman analysis showed a high agreement for all
      mechanical properties. No significant differences were observed in any muscle or
      Achilles tendon properties between days (all p > 0.05). These results indicate
      that the MyotonPRO is reliable for between-day measurements of the mechanical
      properties of lower limb muscles and Achilles tendon in patients with SCI.

PMID- 29599039
TI  - The relationship of whole human vertebral body creep to geometric,
      microstructural, and material properties.
AB  - Creep, the time dependent deformation of a structure under load, is an important
      viscoelastic property of bone and may play a role in the development of permanent
      deformity of the vertebrae in vivo leading to clinically observable spinal
      fractures. To date, creep properties and their relationship to geometric,
      microstructural, and material properties have not been described in isolated
      human vertebral bodies. In this study, a range of image-based measures of
      vertebral bone geometry, bone mass, microarchitecture and mineralization were
      examined in multiple regression models in an effort to understand their
      contribution to creep behavior. Several variables, such as measures of
      mineralization heterogeneity, average bone density, and connectivity density
      persistently appeared as significant effects in multiple regression models
      (adjusted r2: 0.17-0.56). Although further work is needed to identify additional
      tissue properties to fully describe the portion of variability not explained by
      these models, these data are expected to help understand mechanisms underlying
      creep and improve prediction of vertebral deformities that eventually progress to
      a clinically observable fracture.

PMID- 29599042
TI  - Assessing delay and lag in sagittal trunk control using a tracking task.
AB  - Slower trunk muscle responses are linked to back pain and injury. Unfortunately,
      clinical assessments of spine function do not objectively evaluate this important
      attribute, which reflects speed of trunk control. Speed of trunk control can be
      parsed into two components: (1) delay, the time it takes to initiate a movement,
      and (2) lag, the time it takes to execute a movement once initiated. The goal of
      this study is to demonstrate a new approach to assess delay and lag in trunk
      control using a simple tracking task. Ten healthy subjects performed four blocks
      of six trials of trunk tracking in the sagittal plane. Delay and lag were
      estimated by modeling trunk control for predictable and unpredictable (control
      mode) trunk movements in flexion and extension (control direction) at movement
      amplitudes of 2 degrees , 4 degrees , and 6 degrees  (control amplitude). The
      main effect of control mode, direction, and amplitude of movement were compared
      between trial blocks to assess secondary influencers (e.g., fatigue). Only
      control mode was consistent across trial blocks with predictable movements being
      faster than unpredictable for both delay and lag. Control direction and amplitude
      effects on delay and lag were consistent across the first two trial blocks and
      less consistent in later blocks. Given the heterogeneity in the presentation of
      back pain, clinical assessment of trunk control should include different control
      modes, directions, and amplitudes. To reduce testing time and the influence of
      fatigue, we recommend six trials to assess trunk control.

PMID- 29599043
TI  - Reprint of "In response to Tomas, D. et al. (2017). Validation of test portion
      pooling for Salmonella spp. detection in foods. International Journal of Food
      Microbiology, 245: 13-21".

PMID- 29599044
TI  - Response to the letter to Editor for "validation of test portion pooling for
      Salmonella spp. detection in foods".

PMID- 29599045
TI  - Sepsis is important, but there is more.

PMID- 29599047
TI  - Nurses play essential roles in reducing health problems due to climate change.

PMID- 29599046
TI  - Health Care Coverage and Access Among Children, Adolescents, and Young Adults,
      2010-2016: Implications for Future Health Reforms.
AB  - PURPOSE: We examine changes to health insurance coverage and access to health
      care among children, adolescents, and young adults since the implementation of
      the Affordable Care Act. METHODS: Using the National Health Interview Survey,
      bivariate and logistic regression analyses were conducted to compare coverage and
      access among children, young adolescents, older adolescents, and young adults
      between 2010 and 2016. RESULTS: We show significant improvements in coverage
      among children, adolescents, and young adults since 2010. We also find some gains
      in access during this time, particularly reductions in delayed care due to cost.
      While we observe few age-group differences in overall trends in coverage and
      access, our analysis reveals an age-gradient pattern, with incrementally worse
      coverage and access rates for young adolescents, older adolescents, and young
      adults. CONCLUSIONS: Prior analyses often group adolescents with younger
      children, masking important distinctions. Future reforms should consider the
      increased coverage and access risks of adolescents and young adults, recognizing
      that approximately 40% are low income, over a third live in the South, where many
      states have not expanded Medicaid, and over 15% have compromised health.

PMID- 29599048
TI  - IgA-dominant infection-related glomerulonephritis.

PMID- 29599049
TI  - Socioeconomic determinants as risk factors for squamous cell carcinoma of the
      head and neck: a case-control study in Iran.
AB  - Our aim was to assess the association between different components of
      sociodemographic status and the risk of developing squamous cell carcinoma (SCC)
      of the head and neck after we had adjusted for the influence of the known
      behavioural risk factors of smoking and drinking alcohol. We selected 146
      patients with histopathologically-confirmed SCC of the head and neck, and matched
      them for age and sex with 266 healthy controls for this case-control study.
      Personal details, occupation, socioeconomic status, smoking, and alcohol
      consumption were recorded. The association of sociodemographic variables with
      oral cancer was evaluated both separately and with a composite socioeconomic
      index. Chi squared tests, adjusted odds ratios (OR), and 95% CI were computed
      using logistic regression to estimate the effect. There was a significant
      difference between the two groups in the composite socioeconomic index (p<0.001).
      The group with "low" socioeconomic status had the highest risk of oral cancer
      (OR=3.89, 95% CI 1.28 to 11.82). Better-educated people with higher incomes had a
      lower risk of SCC of the head and neck after we had controlled for behavioural
      risk factors. However, marital and employment status and place of residence were
      not significantly associated with risk. Our findings confirm that some
      socioeconomic determinants were associated with the development of oral cancer in
      this study group.

PMID- 29599050
TI  - Unilateral necrosis of the tongue caused by embolisation of cholesterol crystals.
AB  - Cholesterol crystals embolise when an aortic atherosclerotic lesion ruptures and
      cholesterol crystals are scattered and obstruct small peripheral arterioles. Risk
      factors include both iatrogenic factors such as intravascular catheterisation,
      and spontaneous factors for atherosclerosis such as aging, hypertension,
      dyslipidaemia, and smoking. We describe the case of an 83-year-old Japanese man
      who developed unilateral, superficial necrosis of the tongue as a result of
      spontaneous embolisation of cholesterol crystals.

PMID- 29599051
TI  - The effect of diabetes on functional outcomes among individuals with distal
      radial fractures.
AB  - STUDY DESIGN: Prospective cohort study. INTRODUCTION: Diabetes is reported to
      adversely affect outcomes; however, its effect on distal radial fractures (DRF)
      is not well examined. PURPOSE OF THE STUDY: This study investigated the effect of
      diabetes on pain, hand function, physical health status, grip strength, and wrist
      and forearm range of motion among patients with DRF. METHODS: A total of 479
      patients with DRF were classified into patients with and without diabetes based
      on self-report. Patient-Rated Wrist Evaluation assessed pain and hand function.
      The Short Form-12 assessed physical health status. Both questionnaires examined
      DRF recovery at baseline, 3 month, and 1 year. RESULTS: There was a significant
      improvement in Patient-Rated Wrist Evaluation scores over time (69 [19] to 25
      [22]; 76 [15] to 20 [20] for patients with and without diabetes respectively, P <
      .01) with a significant interaction between time and diabetes (P < .01),
      indicating that patients with diabetes recovered more slowly than the rest of the
      cohort. There was an improvement over time on physical status (36 [12] to 45
      [12]; 39 [9] to 50 [9], P < .01), grip strength (16 [7] to 24 [10]; 15 [9] to 24
      [10], P < .01), and range of motion (flexion [42 {14} to 49 {15}; 43 {15} to 54
      {14}, P < .01], extension [45 {11} to 52 {11}; 46 {13} to 53 {12}, P < .01],
      pronation [73 {10} to 77 {9}; 73 {11} to 78 {9}, P < .01], and supination [58
      {17} to 65 {14}; 61 {17} to 70 {12}, P < .01]) for patients with and without
      diabetes, respectively. Patients with diabetes did not differ significantly in
      these secondary outcomes compared to the rest of the cohort. DISCUSSION AND
      CONCLUSION: Although individuals with diabetes had good outcomes, their recovery
      was slower than the rest of the cohort. This may be due to the adverse effect of
      hyperglycemia on bone tissues and small blood vessels. Future studies are
      required to assess how severity and duration of diabetes affect outcomes after
      DRF.

PMID- 29599052
TI  - Can Sepsis Be Detected in the Nursing Home Prior to the Need for Hospital
      Transfer?
AB  - OBJECTIVES: To determine whether and to what extent simple screening tools might
      identify nursing home (NH) residents who are at high risk of becoming septic.
      DESIGN: Retrospective chart audit of all residents who had been hospitalized and
      returned to participating NHs during the study period. SETTING AND PARTICIPANTS:
      A total of 236 NH residents, 59 of whom returned from hospitals with a diagnosis
      of sepsis and 177 who had nonsepsis discharge diagnoses, from 31 community NHs
      that are typical of US nursing homes overall. MEASURES: NH documentation of vital
      signs, mental status change, and medical provider visits 0-12 and 13-72 hours
      prior to the hospitalization. The specificity and sensitivity of 5 screening
      tools were evaluated for their ability to detect residents with incipient sepsis
      during 0-12 and 13-72 hours prior to hospitalization: The Systemic Inflammatory
      Response Syndrome criteria, the quick Sequential Organ Failure Assessment (SOFA),
      the 100-100-100 Early Detection Tool, and temperature thresholds of 99.0 degrees
      F and 100.2 degrees F. In addition, to validate the hospital diagnosis of sepsis,
      hospital discharge records in the NHs were audited to calculate SOFA scores.
      RESULTS: Documentation of 1 or more vital signs was absent in 26%-34% of cases.
      Among persons with complete vital sign documentation, during the 12 hours prior
      to hospitalization, the most sensitive screening tools were the 100-100-100
      Criteria (79%) and an oral temperature >99.0 degrees F (51%); and the most
      specific tools being a temperature >100.2 degrees F (93%), the quick SOFA (88%),
      the Systemic Inflammatory Response Syndrome criteria (86%), and a temperature
      >99.0 degrees F (85%). Many SOFA data points were missing from the record; in
      spite of this, 65% of cases met criteria for sepsis. CONCLUSIONS: NHs need better
      systems to monitor NH residents whose status is changing, and to present that
      information to medical providers in real time, either through rapid medical
      response programs or telemetry.

PMID- 29599053
TI  - The Omega-6:Omega-3 ratio: A critical appraisal and possible successor.
AB  - The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids
      (FAs) has led to a growing interest in the prognostic value that blood levels of
      these FAs might have vis-a-vis cardiovascular and neurocognitive diseases. The
      measurement and expression of n-3 FA levels is not straight-forward, however, and
      a wide variety of means of expression of n-3 FA status have been used in research
      and clinical medicine. This has led to considerable confusion as to what
      "optimal" n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread
      use, but this apparently simple metric has both theoretical and practical
      difficulties that have contributed to misunderstandings in this field. Just as
      the once-popular polyunsaturated:saturated FA ratio has largely disappeared from
      the nutritional and medical literature, it may be time to replace the n-6:n-3
      ratio with a newer metric that focuses on the primary deficiency in Western diets
      - the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega
      3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.

PMID- 29599054
TI  - Corrigendum to "Rheological properties of microalgae slurry for application in
      hydrothermal pretreatment systems" [Bioresour. Technol. 249 (2018) 599-604].

PMID- 29599055
TI  - Effect of participation in a park-based afterschool program on cardiovascular
      disease risk among severely obese youth.
AB  - OBJECTIVES: The prevalence of severe obesity in youth is rising, despite reports
      of obesity rates stabilizing overall. While reports on treatment outcomes for
      youth with severe obesity (bariatric surgery, behavioral and pharmacological
      treatments) exist, very few community-based programs have reported changes in
      health outcomes in this population. We assessed changes in cardiovascular health
      risk profiles among racial/ethnic minority youth with severe obesity who
      participated in Fit2PlayTM, a park-based afterschool health promotion program.
      STUDY DESIGN: A longitudinal cohort study. METHODS: Children aged 6-14 years (N =
      1546, 51% Hispanic, 44% non-Hispanic black) who participated in the Fit2PlayTM in
      one of 34 urban park sites for one school year over five separate school years
      (2010-2015) had height, weight, four-site skinfold thicknesses, systolic blood
      pressure (SBP)/diastolic blood pressure (DBP), fitness tests, and a
      health/wellness knowledge test collected at the beginning and end of the school
      year. Two-level repeated measures mixed models examined changes in cardiovascular
      health outcomes (body mass index [BMI], skinfold thickness, systolic/diastolic
      blood pressure percentile [SBPP/DBPP], cardiorespiratory fitness [PACER]) in
      youth with severe obesity over 1- and 2-year follow-up. RESULTS: Compared with
      baseline, BMI decreased 13% (incidence rate ratio [IRR] 95% confidence interval
      [CI]: 0.83-0.90), sumof skinfold thicknesses decreased 5% (IRR 95% CI: 0.91
      0.99), SBPP decreased 5% (IRR 95% CI: 0.90-0.99), DBPP decreased 19% (IRR 95% CI:
      0.77-0.86), and PACER scores increased 12% (IRR 95% CI: 1.0-1.27) after two years
      of participation in the Fit2PlayTM program. CONCLUSIONS: Findings here support
      community/park-based youth programs as effective and accessible treatment options
      for reducing cardiovascular disease risk among youth with severe obesity.

PMID- 29599056
TI  - Building evaluation capacity in Ontario's public health units: promising
      practices and strategies.
AB  - OBJECTIVES: This article presents the findings of a project focusing on building
      evaluation capacity in 10 Ontario public health units. The study sought to
      identify effective strategies that lead to increased evaluation capacity in the
      participating organizations. STUDY DESIGN: This study used a qualitative,
      multiple case research design. METHODS: An action research methodology was used
      to design customized evaluation capacity building (ECB) strategies for each
      participating organization, based on its specific context and needs. This
      methodological approach also enabled monitoring and assessment of each strategy,
      based on a common set of reporting templates. A multiple case study was used to
      analyze the findings from the 10 participating organizations and derive higher
      level findings. RESULTS: The main findings of the study show that most of the
      strategies used to increase evaluation capacity in public health units are
      promising, especially those focusing on developing the knowledge, skills, and
      attitudes of health unit staff and managers. Facilitators to ECB strategies were
      the engagement of all staff members, the support of leadership, and the existence
      of organizational tools and infrastructure to support evaluation. It is also
      essential to recognize that ECB takes time and resources to be successful.
      CONCLUSIONS: The design and implementation of ECB strategies should be based on
      organizational needs. These can be assessed using a standardized instrument, as
      well as interviews and staff surveys. The implementation of a multicomponent
      approach (i.e. several strategies implemented simultaneously) is also linked to
      better ECB outcomes in organizations.

PMID- 29599057
TI  - The challenging issue of postcolonoscopy colorectal carcinomas.

PMID- 29599058
TI  - Retinal vasculitis and Eales disease.

PMID- 29599059
TI  - Usefulness of brain magnetic resonance in the diagnosis of cerebrotendinous
      xanthomatosis.

PMID- 29599060
TI  - Seasonal variabilities in chemical compounds and acidity of aerosol particles at
      urban site in the west Pacific.
AB  - Mass concentrations of chemical compounds in both PM2.5 (particle aerodynamic
      diameter, Dp < 2.5 MUm) and PM2.5-10 (2.5 < Dp < 10 MUm), and acidity of aerosol
      particles were measured at an urban site in western Japan using a continuous
      dichotomous Aerosol Chemical Speciation Analyzer (ACSA-12) throughout 2014. Mass
      concentrations of both PM2.5 and sulfate had distinct seasonal variabilities with
      maxima in spring and winter, mostly due to long-range transport with the
      prevailing westerly wind. Mass concentration of nitrate in PM2.5 (fNO3) showed an
      obvious warm-season-low and cold-season-high pattern as a result of both gas
      aerosol phase equilibrium processes under high temperature conditions as well as
      transport. Nitrate in PM2.5-10 (cNO3) increased during long-range transport of
      dust, implying the great importance of heterogeneous processes at the surface of
      coarse mode particles. In this study, Delta[H+] (derived from the difference in
      pH of extract liquid with/without sampling) was used to indicate the acidity of
      particles. We found that acidity of particles in PM2.5 (fDeltaH) was mostly
      positive with a maximum in August because of the large fraction of nitrate and
      sulfate. Acidity of particles in PM2.5-10 (cDeltaH) was negative in winter and
      spring due to presence of alkaline matter from crustal sources. This study
      highlights the great importance of anthropogenic pollutants on the acidity of
      particles in the western Pacific Ocean and further impact on the marine
      environment and climate.

PMID- 29599061
TI  - Cholesteatoma labyrinthine fistula: prevalence and impact.
AB  - INTRODUCTION: Labyrinthine fistula is one of the most common complications
      associated with cholesteatoma. It represents an erosive loss of the endochondral
      bone overlying the labyrinth. Reasons for cholesteatoma-induced labyrinthine
      fistula are still poorly understood. OBJECTIVE: Evaluate patients with
      cholesteatoma, in order to identify possible risk factors or clinical findings
      associated with labyrinthine fistula. Secondary objectives were to determine the
      prevalence of labyrinthine fistula in the study cohort, to analyze the role of
      computed tomography and to describe the hearing results after surgery. METHODS:
      This retrospective cohort study included patients with an acquired middle ear
      cholesteatoma in at least one ear with no prior surgery, who underwent audiometry
      and tomographic examination of the ears or surgery at our institution. Hearing
      results after surgery were analyzed according to the labyrinthine fistula
      classification and the employed technique. RESULTS: We analyzed a total of 333
      patients, of which 9 (2.7%) had labyrinthine fistula in the lateral semicircular
      canal. In 8 patients, the fistula was first identified on image studies and
      confirmed at surgery. In patients with posterior epitympanic and two-route
      cholesteatomas, the prevalence was 5.0%; and in cases with remaining
      cholesteatoma growth patterns, the prevalence was 0.6% (p=0.16). In addition, the
      prevalence ratio for labyrinthine fistula between patients with and without
      vertigo was 2.1. Of patients without sensorineural hearing loss before surgery,
      80.0% remained with the same bone conduction thresholds, whereas 20.0% progressed
      to profound hearing loss. Of patients with sensorineural hearing loss before
      surgery, 33.33% remained with the same hearing impairment, whereas 33.33% showed
      improvement of the bone conduction thresholds' Pure Tone Average. CONCLUSION:
      Labyrinthine fistula must be ruled out prior to ear surgery, particularly in
      cases of posterior epitympanic or two-route cholesteatoma. Computed tomography is
      a good diagnostic modality for lateral semicircular canal fistula. Sensorineural
      hearing loss can occur post-surgically, even in previously unaffected patients
      despite the technique employed.

PMID- 29599062
TI  - [Harlequin syndrome: Two sides of the same disease].

PMID- 29599063
TI  - [Management of heart failure in cardiology and primary care (MICCAP) program:
      Improving the management of patients with heart failure].
AB  - Despite current treatments, morbidity and mortality of patients with heart
      failure remain high. The late diagnosis of heart failure, the insufficient heart
      failure treatment (i.e. not using the appropriate drugs, prescribing lower doses
      of drugs than recommended, etc.), and a poor coordination between different
      health care levels, may explain, at least in part, these figures. The Management
      of Heart Failure in Cardiology and Primary Care (MICCAP) program has been
      developed with the aim of optimising the integrated management of patients with
      heart failure between Primary Care and Cardiology, through the improvement of
      coordination between both health care levels. This includes continuous medical
      education to reinforce the diagnostic and therapeutic skills of general
      practitioners in the field of heart failure. The rationale and objectives of the
      MICCAP program are summarised in this article.

PMID- 29599064
TI  - Black Country Lungs: a moving exploration of COPD in a post-industrial community.

PMID- 29599066
TI  - Experimental and numerical study of platelets rolling on a von Willebrand factor
      coated surface.
AB  - Blood platelets circulate in the blood and adhere to wounded vessels to initiate
      coagulation and healing. The first step of this process is the capture of flowing
      platelets by adhesive molecules located at the wounded vessel wall. In this
      article, we study the transport of fixed blood platelets in a microfluidic
      channel coated with von Willebrand factor (vWF), a large multimeric protein
      expressed by endothelial cells in the vicinity of wounds. We measure the number
      of platelets adsorbed at the channel surface as a function of both time and
      space. Experimental results are compared with a new transport model. We show that
      transverse diffusion is an important feature of our model, while the rolling
      behaviour of the bounded platelets can be neglected.

PMID- 29599065
TI  - The retinoid X receptor agonist, 9-cis UAB30, inhibits cutaneous T-cell lymphoma
      proliferation through the SKP2-p27kip1 axis.
AB  - BACKGROUND: Bexarotene (Targretin(r)) is currently the only FDA approved retinoid
      X receptor (RXR) -selective agonist for the treatment of cutaneous T-cell
      lymphomas (CTCLs). The main side effects of bexarotene are hypothyroidism and
      elevation of serum triglycerides (TGs). The novel RXR ligand, 9-cis UAB30 (UAB30)
      does not elevate serum TGs or induce hypothyroidism in normal subjects.
      OBJECTIVES: To assess preclinical efficacy and mechanism of action of UAB30 in
      the treatment of CTCLs and compare its action with bexarotene. METHODS: With
      patient-derived CTCL cell lines, we evaluated UAB30 function in regulating
      growth, apoptosis, cell cycle check points, and cell cycle-related markers.
      RESULTS: Compared to bexarotene, UAB30 had lower half maximal inhibitory
      concentration (IC50) values and was more effective in inhibiting the G1 cell
      cycle checkpoint. Both rexinoids increased the stability of the cell cycle
      inhibitor, p27kip1 protein, in part, through targeting components involved in the
      ubiquitination-proteasome system: 1) decreasing SKP2, a F-box protein that binds
      and targets p27kip1 for degradation by 26S proteasome and 2) suppressing 20S
      proteasome activity (cell line-dependent) through downregulation of PSMA7, a
      component of the 20S proteolytic complex in 26S proteasome. CONCLUSIONS: UAB30
      and bexarotene induce both early cell apoptosis and suppress cell proliferation.
      Inhibition of the G1 to S cell cycle transition by rexinoids is mediated, in
      part, through downregulation of SKP2 and/or 20S proteasome activity, leading to
      increased p27kip1 protein stability. Because UAB30 has minimal effect in
      elevating serum TGs and inducing hypothyroidism, it is potentially a better
      alternative to bexarotene for the treatment of CTCLs.

PMID- 29599067
TI  - Editor's Choice - A Comparison of Clinical Outcomes Between Primary Bypass and
      Secondary Bypass After Failed Plain Balloon Angioplasty in the Bypass versus
      Angioplasty for Severe Ischaemia of the Limb (BASIL) Trial.
AB  - OBJECTIVE: Chronic limb threatening ischaemia (CLTI) is a growing global health
      problem. The UK NIHR HTA funded BASIL trial is still the only randomised
      controlled trial to have compared a "bypass surgery first" with a "plain balloon
      angioplasty (PBA) first" strategy for the management of CLTI. In patients who
      were likely to survive for 2 years and had a suitable vein, primary bypass (PB)
      was associated with better clinical outcomes. Furthermore, PBA was associated
      with a high technical and clinical failure rate and many went on to have
      secondary bypass (SB). This study aimed at comparing clinical outcomes following
      PB and SB in the BASIL trial. METHODS: Demographic, procedural, and outcome data
      were obtained from the BASIL case report forms. Outcomes were amputation free
      survival (AFS), limb salvage (LS), overall survival (OS), and freedom from
      revascularisation (FFR). The SB cohort comprises patients whose first trial
      intervention was PBA and who subsequently underwent bypass during follow up. The
      PB cohort comprises those patients whose first trial intervention was bypass.
      RESULTS: The 190 PB and 49 SB patients were well matched except that the SB
      patients were more likely to be current smokers. At a median of 7 years, PB was
      associated with better AFS (PB 60% vs. SB 40%; HR 1.58, p = .04), LS (PB 85% vs.
      SB 73%, p = .06), and OS (PB 68% vs. 51%, p = .06). FFR was equivalent (PB 53%
      vs. 53%, p = .3). CONCLUSION: In the BASIL trial, clinical outcomes following PB
      were significantly better than in patients undergoing SB after failed PBA. Prior
      to treating patients with CLTI with primary PBA, clinicians should consider that
      if this should fail, the outcome of attempted subsequent bypass is likely to be
      significantly worse than if PB were attempted.

PMID- 29599069
TI  - Blood Lead Levels of Children in Flint, Michigan: 2006-2016.
AB  - OBJECTIVE: We evaluated the increases in blood lead levels (BLLs) observed in
      young children in Flint, Michigan, during their exposure to corrosive Flint River
      water during the years 2014 and 2015 and compared their BLLs to those of Flint
      children measured during the years 2006-2013 and 2016. STUDY DESIGN: This was a
      retrospective study design using BLLs extracted from databases from 2006 to 2016.
      We analyzed a population sample of 15 817 BLLs from children aged <=5 years with
      potential exposure to contaminated Flint River water. Percentages of BLLs >=5.0
      ug/dL and geometric mean (GM) BLLs were analyzed over time. RESULTS: A
      significant decline in the percentages of BLLs >=5.0 ug/dL from 11.8% in 2006 to
      3.2% in 2016 was observed (P < .001). GM +/- SE BLLs decreased from 2.33 +/- 0.04
      ug/dL in 2006 to 1.15 +/- 0.02 ug/dL in 2016 (P < .001). GM BLLs increased twice:
      from 1.75 +/- 0.03 ug/dL to 1.87 +/- 0.03 ug/dL (2010-2011) and from 1.19 +/-
      0.02 ug/dL to 1.30 +/- 0.02 ug/dL (2014-2015). Overall, from 2006 to 2016, there
      was a 72.9% decrease in the percentage of children with BLLs >=5.0 ug/dL and a
      50.6% decrease in GM BLLs. CONCLUSION: These findings suggest that the 11 year
      trend of annual decreases in BLLs in children in Flint, Michigan, reversed to a
      degree consistent with random variation from 2010 to 2011, and again during the
      exposure to Flint River water in 2014-2015. Historically, public health efforts
      to reduce BLLs of young children in Flint have been effective over the 11-year
      period studied.

PMID- 29599071
TI  - Maintaining normothermia: Why and how?
AB  - A high incidence of postnatal hypothermia has been reported in high-as well low
      resource countries and it remains an independent predictor of neonatal morbidity
      and mortality, especially in very preterm infants in all settings. The
      temperature of newly born infants should be maintained between 36.5 and 37.5 
      degrees C after birth through admission and stabilization. Interventions to
      achieve this may include environmental temperature 23-25  degrees C, use of
      radiant warmers, exothermic mattresses, woollen or plastic caps, plastic wraps,
      humidified and heated gases. Skin-to-skin contact has been used, especially in
      low-resource settings. The combinations of these interventions applied to quality
      improvement initiatives, including staff training, use of checklists, and
      continuous feedback with the staff involved in the management of the neonate, are
      key factors to prevent heat loss from delivery room to admission to the neonatal
      intensive care unit. The admission temperature should be recorded as a predictor
      of outcomes as well as a quality indicator.

PMID- 29599068
TI  - Acute Responses to Diuretic Therapy in Extremely Low Gestational Age Newborns:
      Results from the Prematurity and Respiratory Outcomes Program Cohort Study.
AB  - OBJECTIVE: To determine if daily respiratory status improved more in extremely
      low gestational age (GA) premature infants after diuretic exposure compared with
      those not exposed in modern neonatal intensive care units. STUDY DESIGN: The
      Prematurity and Respiratory Outcomes Program (PROP) was a multicenter
      observational cohort study of 835 extremely premature infants, GAs of 230/7-286/7
      weeks, enrolled in the first week of life from 13 US tertiary neonatal intensive
      care units. We analyzed the PROP study daily medication and respiratory support
      records of infants <=34 weeks postmenstrual age. We determined whether there was
      a temporal association between the administration of diuretics and an acute
      change in respiratory status in premature infants in the neonatal intensive care
      unit, using an ordered categorical ranking of respiratory status. RESULTS:
      Infants in the diuretic exposed group of PROP were of lower mean GA and lower
      mean birth weight (P < .0001). Compared with infants unexposed to diuretics, the
      probability (adjusted for infant characteristics including GA, birth weight, sex,
      and respiratory status before receiving diuretics) that the exposed infants were
      on a higher level of respiratory support was significantly greater (OR, >1) for
      each day after the initial day of diuretic exposure. CONCLUSIONS: Our analysis
      did not support the ability of diuretics to substantially improve the extremely
      premature infant's respiratory status. Further study of both safety and efficacy
      of diuretics in this setting are warranted. TRIAL REGISTRATION:
      Clinicaltrials.gov: NCT01435187.

PMID- 29599070
TI  - Postoperative D-dimer predicts venous thromboembolism in patients undergoing
      urologic tumor surgery.
AB  - PURPOSE: We examined the incidence of pulmonary thromboembolism (PE) and deep
      venous thromboembolism (DVT) in patients who underwent urologic tumor surgery.
      The aim of this study was to investigate the postoperative D-dimer for prediction
      of venous thromboembolism events (VTE), as well as to identify other risk factors
      associated with the occurrence of thromboembolisms. PATIENTS AND METHODS: This
      was a prospective observational cohort study, which included 1,269 patients who
      underwent major urologic tumor surgery, from August 2015 to February 2017, at our
      center. Data comprising age, sex, body mass index, Charlson comorbidity index,
      type of surgery, Caprini score, postoperative D-dimer levels, and other
      laboratory tests were collected for analyses. Lower limb venous ultrasound was
      performed before surgery and the day before hospital discharge to measure DVT.
      Computerized tomography or ventilation/perfusion lung scan was applied to detect
      PE. RESULTS: The overall incidence of VTE was 2.4% (31 cases) in 1,269 patients,
      consisting of 23 PE events and 9 DVT events. Patients undergoing radical
      cystectomy were most likely to suffer VTE (4.3%). The optimal cutoff value for
      postoperative D-dimer was 0.98MUg/ml, according to the receiver operating
      characteristic curve analysis, with a sensitivity of 83.9%, and a specificity of
      80.0%. On multivariate analysis, hypertension (odds ratio, OR = 2.5, 95% CI: 1.1
      5.7; P = 0.026), Charlson comorbidity index >= 2 (OR = 5.6, 95% CI: 2.2-14.6;
      P<0.001), and D-dimer lever >= 1MUg/ml on postoperative day 1 (OR = 12.52, 95%
      CI: 4.6-35.2; P<0.001) were independently associated with VTE after urologic
      tumor surgery. CONCLUSIONS: The overall incidence of urologic-tumor-surgery
      associated VTE in an Asian population is similar to those reported in European
      and North American series. Elevated D-dimer early after operation is an
      independent predictor of VTE in patients undergoing urologic tumor surgery. In
      addition, hypertension and the Charlson comorbidity index are both important
      clinical risk factors. The Caprini score recommended by the guideline is
      inadequate in this study population. The postoperative D-dimer plasma level is a
      more reliable marker for identifying patients at high-risk of developing venous
      thromboembolisms.

PMID- 29599072
TI  - Preoperative immobility significantly impacts the risk of postoperative
      complications in bariatric surgery patients.
AB  - BACKGROUND: Preoperative immobility in general surgery patients has been
      associated with an increased risk of postoperative complications. It is unknown
      if immobility affects bariatric surgery outcomes. OBJECTIVES: The aim of this
      study was to determine the impact of immobility on 30-day postoperative bariatric
      surgery outcomes. SETTING: This study took place at a university hospital in the
      United States. METHODS: The Metabolic and Bariatric Surgery Accreditation and
      Quality Improvement Program 2015 data set was queried for primary minimally
      invasive bariatric procedures. Preoperative immobility was defined as limited
      ambulation most or all the time. Logistic regression analysis was performed to
      determine if immobile patients are at increased risk (odds ratio [OR]) for 30-day
      complications. RESULTS: There were 148,710 primary minimally invasive bariatric
      procedures in 2015. Immobile patients had an increased risk of mortality (OR
      4.59, P<.001) and greater operative times, length of stay, reoperation rates, and
      readmissions. Immobile patients had a greater risk of multiple complications,
      including acute renal failure (OR 6.42, P<.001), pulmonary embolism (OR 2.44, P =
      .01), cardiac arrest (OR 2.81, P = .05), and septic shock (OR 2.78, P = .02).
      Regardless of procedure type, immobile patients had a higher incidence of
      perioperative morbidity compared with ambulatory patients. CONCLUSIONS: This
      study is the first to specifically assess the impact of immobility on 30-day
      bariatric surgery outcomes. Immobile patients have a significantly increased risk
      of morbidity and mortality. This study provides an opportunity for the
      development of multiple quality initiatives to improve the safety and
      perioperative complication profile for immobile patients undergoing bariatric
      surgery.

PMID- 29599073
TI  - Adjustable gastric banded plication versus sleeve gastrectomy: the role of
      gastrectomy in weight loss.
AB  - BACKGROUND: Laparoscopic adjustable gastric banded plication (LAGBP) is a
      procedure that has a stomach volume similar to the sleeve gastrectomy (SG). It
      has shown promising results but has not been adopted widely. OBJECTIVE: To
      determine the difference gastrectomy has on weight loss and complications.
      SETTING: Private practice, United States. METHODS: A retrospective, matched
      cohort analysis of LAGBP and SG patients was found through matching body mass
      index and sex for each LAGBP to a SG patient. Body mass index, percentage excess
      weight loss, and total weight loss percentage were analyzed. Complication data
      were also collected on a short- (<30 d) and long- (>30 d) term basis.
      Complication rates were then compared. Data were analyzed through descriptive
      statistics. RESULTS: Patients who received SG lost more body mass index,
      percentage excess weight loss, and total weight loss percentage at 1 year and
      started to gain weight between 1 and 2 years. LAGBP patients weight loss also
      peaked at 1 year but maintained their weight loss to year 2. SG patients lost
      more weight at all time points, and the difference was statistically significant
      (P<.05). LAGBP and SG patients had statistically similar rates of short- and long
      term complication rates. In the LAGBP group (57 patients) 5, 9, 13, 14, 14, and
      17 patients were lost to follow-up at 3, 6, 9, 12, 18, and 24 months,
      respectively. In the SG group (57 patients) 11, 10, 11, 13, 20, and 29 patients
      were lost to follow-up at 3, 6, 9, 12, 18, and 24 months, respectively.
      CONCLUSION: Both procedures have peak weight loss at 1 year with acceptable
      complication rates. However, the SG starts to regain weight while the LAGBP shows
      weight stability. More time is needed to see if the weight loss curves will
      intersect or if the late band complications will also happen with the LAGBP as
      they have with band placement without plication.

PMID- 29599074
TI  - Radiographic evaluation of the normal ankle joint in children and adolescent.
AB  - BACKGROUND: The purpose of this study was to determine the reliability of
      numerous radiographic measurements of the skeletally immature ankle joint, timing
      of ossification of medial malleolus and appearance of tibial incisura and
      differences in the values of radiographic measurements based on age and sex.
      METHODS: This study included 590 subjects (0-15 years), who underwent ankle AP,
      lateral and mortise radiographs. Presence of the medial malleolus and incisura
      fibularis were recorded. Tibiofibular overlap, tibiofibular clear space, medial
      clear space, talar tilt, talocrural angle, relative fibular width and fibular
      position were measured. RESULTS: All radiographic measurements showed good to
      excellent intraobserver and interobserver reliability (ICCs, 0.603 to 0.949). The
      timing of ossification of medial malleolus and appearance of tibial incisura
      between boys and girls were not different. Tibiofibular clear space on mortise
      views, and medial clear space on AP and mortise view significantly decreased by
      age. Tibiofibular overlap on AP and mortise views, relative fibular width on AP
      view significantly increased by age. Talocrural angle, tibiofibular overlap on AP
      view, tibiofibular clear space on AP and mortise views, medial clear space on AP
      and mortise views and fibular position were significantly larger in boys than in
      girls. The difference in tibiofibular overlap, tibiofibular clear space and
      medial clear space on AP view of both sides was <50% in 97.1%, 93.1%, and 97.2%
      of patients, respectively. The difference in tibiofibular overlap, tibiofibular
      clear space and medial clear space on mortise view of both sides was <50% in
      98.0%, 96.5%, and 100% of patients, respectively. CONCLUSIONS: For skeletally
      immature patients, the criteria for absolute radiographic values used in adults
      to assess distal tibiofibular syndesmosis or deltoid ligament injury cannot be
      applied, but comparison of both sides of ankle joint could help physicians to
      predict the need for additional evaluations.

PMID- 29599075
TI  - Percutaneous endoscopic gastrostomy in patients with amyotrophic lateral
      sclerosis: Mortality and complications.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      that causes severe dysphagia and weight loss. Percutaneous endoscopic gastrostomy
      (PEG) is currently the technique of choice for the enteral nutrition of these
      patients. OBJECTIVES: To analyse mortality and complications in a series of
      patients diagnosed with ALS who underwent PEG, and to evaluate factors related to
      patient survival after the procedure. MATERIAL AND METHODS: We performed a
      prospective, observational study including all patients diagnosed with ALS and
      treated by our hospital's Gastroenterology Department in the period 1997-2013. We
      studied mortality, complications, and clinical and biochemical parameters, and
      correlated these with the survival rate. RESULTS: The study included a total of
      57 patients, of whom 49 were ultimately treated with PEG. ALS onset was bulbar in
      30 patients and spinal in 19. Mortality during the procedure and at 30 days was
      2% (n = 1). Six patients (12.2%) experienced major complications; 17 (34.7%)
      experienced less serious complications which were easily resolved with
      conservative treatment. No significant differences were observed in forced vital
      capacity, albumin level, or age between patients with (n = 6) and without (n =
      43) major complications. CONCLUSIONS: PEG is an effective, relatively safe
      procedure for the enteral nutrition of patients with ALS, although not without
      morbidity and mortality. Neither forced vital capacity nor the form of
      presentation of ALS were associated with morbidity in PEG.

PMID- 29599076
TI  - Characteristics of PPT1 and TPP1 enzymes in neuronal ceroid lipofuscinosis (NCL)
      1 and 2 by dried blood spots (DBS) and leukocytes and their application to
      newborn screening.
AB  - We first characterized PPT1 and TPP1 enzymes in dried blood spots (DBS),
      plasma/serum, and leukocytes/lymphocytes using neuronal ceroid lipofuscinosis
      (NCL) 1 and 2 patients and control subjects. PPT1 enzyme had only one acid form
      in control DBS, plasma/serum, and leukocytes/lymphocytes and showed deficient
      activities in these samples from NCL 1 patients. Conversely, TPP1 enzymes in
      control DBS and leukocytes/lymphocytes consisted of two forms, an acidic form and
      a neutral form, whereas serum TPP1 enzyme had only a neutral form. In control
      subjects, the optimal pH of PPT1 enzyme in DBS, plasma/serum, and
      leukocytes/lymphocytes was 4.5 to 5.0 in the acidic form, whereas TPP1 enzyme in
      control DBS and leukocytes/lymphocytes was pH 4.5 and 6.5, respectively. In NCL 1
      and 2, both PPT1 and TPP1 enzyme activities in DBS, plasma, and
      leukocytes/lymphocytes were markedly reduced in acidic pH, whereas heterozygotes
      of NCL 1 and 2 in the acidic form showed intermediate activities between patients
      and control subjects. In neutral conditions, pH 6.0, the PPT1 enzyme activities
      in NCL 1 patients showed rather higher residual activities and intermediate
      activities in heterozygotes in NCL 1, which was probably caused by mutated
      proteins in three cases with NCL 1 patients. TPP1 enzyme activities at neutral pH
      6.5 to 7.0 in DBS and leukocytes/lymphocytes showed higher enzyme activities in
      NCL 2 patients and heterozygotes. The reason for the increases of neutral TPP1
      enzyme activities at pH 6.5 to 7.0 in NCL 2 DBS and leukocytes/lymphocytes, is
      obscure, but possibly caused by secondary activation of neutral TPP1 enzyme due
      to the absence of the acidic form. Interestingly, TPP1 activity in serum only
      consisted of a neutral form, no acidic form, and was not deficient in any NCL 2
      patient. Therefore, we can diagnose NCL 1 patients by plasma/serum enzyme assay
      of PPT1, but not diagnose NCL 2 by serum TPP1 enzyme assay. A pilot study of
      newborn screening of NCL 1 and 2 has been established by more than 1000 newborn
      DBS assays. Using this assay system, we will be able to perform newborn screening
      of NCL 1 and 2 by DBS.

PMID- 29599077
TI  - Delineating the global challenges of hepatitis B virus infection.

PMID- 29599079
TI  - Efficient In Vivo Liver-Directed Gene Editing Using CRISPR/Cas9.
AB  - In vivo tissue-specific genome editing at the desired loci is still a challenge.
      Here, we report that AAV9-delivery of truncated guide RNAs (gRNAs) and Cas9 under
      the control of a computationally designed hepatocyte-specific promoter lead to
      liver-specific and sequence-specific targeting in the mouse factor IX (F9) gene.
      The efficiency of in vivo targeting was assessed by T7E1 assays, site-specific
      Sanger sequencing, and deep sequencing of on-target and putative off-target
      sites. Though AAV9 transduction was apparent in multiple tissues and organs, Cas9
      expression was restricted mainly to the liver, with only minimal or no expression
      in other non-hepatic tissues. Consequently, the insertions and deletion (indel)
      frequency was robust in the liver (up to 50%) in the desired target loci of the
      F9 gene, with no evidence of targeting in other organs or other putative off
      target sites. This resulted in a substantial loss of FIX activity and the
      emergence of a bleeding phenotype, consistent with hemophilia B. The in vivo
      efficacy of the truncated gRNA was as high as that of full-length gRNA. Cas9
      expression was transient in neonates, representing an attractive "hit-and-run"
      paradigm. Our findings have potentially broad implications for somatic gene
      targeting in the liver using the CRISPR/Cas9 platform.

PMID- 29599080
TI  - Exosomes from Endothelial Progenitor Cells Improve the Outcome of a Murine Model
      of Sepsis.
AB  - Microvascular dysfunction leads to multi-organ failure and mortality in sepsis.
      Our previous studies demonstrated that administration of exogenous endothelial
      progenitor cells (EPCs) confers protection in sepsis as evidenced by reduced
      vascular leakage, improved organ function, and increased survival. We hypothesize
      that EPCs protect the microvasculature through the exosomes-mediated transfer of
      microRNAs (miRNAs). Mice were rendered septic by cecal ligation and puncture
      (CLP), and EPC exosomes were administered intravenously at 4 hr after CLP. EPC
      exosomes treatment improved survival, suppressing lung and renal vascular
      leakage, and reducing liver and kidney dysfunction in septic mice. EPC exosomes
      attenuated sepsis-induced increases in plasma levels of cytokines and chemokine.
      Moreover, we determined miRNA contents of EPC exosomes with next-generation
      sequencing and found abundant miR-126-3p and 5p. We demonstrated that exosomal
      miR-126-5p and 3p suppressed LPS-induced high mobility group box 1 (HMGB1) and
      vascular cell adhesion molecule 1 (VCAM1) levels, respectively, in human
      microvascular endothelial cells (HMVECs). Inhibition of microRNA-126-5p and 3p
      through transfection with microRNA-126-5p and 3p inhibitors abrogated the
      beneficial effect of EPC exosomes. The inhibition of exosomal microRNA-126 failed
      to block LPS-induced increase in HMGB1 and VCAM1 protein levels in HMVECs and
      negated the protective effect of exosomes on sepsis survival. Thus, EPC exosomes
      prevent microvascular dysfunction and improve sepsis outcomes potentially through
      the delivery of miR-126.

PMID- 29599078
TI  - Global prevalence, treatment, and prevention of hepatitis B virus infection in
      2016: a modelling study.
AB  - BACKGROUND: The 69th World Health Assembly approved the Global Health Sector
      Strategy to eliminate viral hepatitis by 2030. Although no virological cure
      exists for hepatitis B virus (HBV) infection, existing therapies to control viral
      replication and prophylaxis to minimise mother-to-child transmission make
      elimination of HBV feasible. We aimed to estimate the national, regional, and
      global prevalence of HBsAg in the general population and in the population aged 5
      years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.
      METHODS: In this modelling study, we used a Delphi process that included a
      literature review in PubMed and Embase, followed by interviews with experts, to
      quantify the historical epidemiology of HBV infection. We then used a dynamic HBV
      transmission and progression model to estimate the country-level and regional
      level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on
      disease burden. FINDINGS: We developed models for 120 countries, 78 of which were
      populated with data approved by experts. Using these models, we estimated that
      the global prevalence of HBsAg in 2016 was 3.9% (95% uncertainty interval [UI]
      3.4-4.6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of
      these infections, around 29 million (10%) were diagnosed, and only 4.8 million
      (5%) of 94 million individuals eligible for treatment actually received antiviral
      therapy. Around 1.8 (1.6-2.2) million infections were in children aged 5 years,
      with a prevalence of 1.4% (1.2-1.6). We estimated that 87% of infants had
      received the three-dose HBV vaccination in the first year of life, 46% had
      received timely birth-dose vaccination, and 13% had received hepatitis B
      immunoglobulin along with the full vaccination regimen. Less than 1% of mothers
      with a high viral load had received antiviral therapy to reduce mother-to-child
      transmission. INTERPRETATION: Our estimate of HBV prevalence in 2016 differs from
      previous studies, potentially because we took into account the effect of infant
      prophylaxis and early childhood vaccination, as well as changing prevalence over
      time. Although some regions are well on their way to meeting prophylaxis and
      prevalence targets, all regions must substantially scale-up access to diagnosis
      and treatment to meet the global targets. FUNDING: John C Martin Foundation.

PMID- 29599081
TI  - Improvement of early detection of breast cancer through collaborative multi
      country efforts: Medical physics component.
AB  - PURPOSE: The International Atomic Energy Agency (IAEA) through a Coordinated
      Research Project on "Enhancing Capacity for Early Detection and Diagnosis of
      Breast Cancer through Imaging", brought together a group of mammography
      radiologists, medical physicists and radiographers; to investigate current
      practices and improve procedures for the early detection of breast cancer by
      strengthening both the clinical and medical physics components. This paper
      addresses the medical physics component. METHODS: The countries that participated
      in the CRP were Bosnia and Herzegovina, Costa Rica, Egypt, India, Kenya, the
      Frmr. Yug. Rep. of Macedonia, Mexico, Nigeria, Pakistan, Philippines, Slovenia,
      Turkey, Uganda, United Kingdom and Zambia. Ten institutions participated using
      IAEA quality control protocols in 9 digital and 3 analogue mammography equipment.
      A spreadsheet for data collection was generated and distributed. Evaluation of
      image quality was done using TOR MAX and DMAM2 Gold phantoms. RESULTS: QC results
      for analogue equipment showed satisfactory results. QC tests performed on digital
      systems showed that improvements needed to be implemented, especially in
      thickness accuracy, signal difference to noise ratio (SDNR) values for achievable
      levels, uniformity and modulation transfer function (MTF). Mean glandular dose
      (MGD) was below international recommended levels for patient radiation
      protection. Evaluation of image quality by phantoms also indicated the need for
      improvement. CONCLUSIONS: Common activities facilitated improvement in
      mammography practice, including training of medical physicists in QC programs and
      infrastructure was improved and strengthened; networking among medical physicists
      and radiologists took place and was maintained over time. IAEA QC protocols
      provided a uniformed approach to QC measurements.

PMID- 29599082
TI  - Appropriateness of tricyclic antidepressants in the geriatric population: A
      critical interpretation of existing literature.

PMID- 29599083
TI  - Corrigendum to 'The effect of perioperative glucose control on postoperative
      insulin resistance' [Clin Nutr 31 (5) (2012) 676-681].

PMID- 29599084
TI  - Red blood cells, compasses and snap shots.

PMID- 29599085
TI  - Fetal presentation of congenital dyserythropoietic anemia type 1 with novel
      compound heterozygous CDAN1 mutations.
AB  - The congenital dyserythropoietic anemias are a heterogeneous group of disorders
      characterized by anemia and ineffective erythropoiesis. Congenital
      dyserythropoietic anemia type I (CDA1) can present in utero with hydrops fetalis,
      but more often it presents in childhood or adulthood with moderate macrocytic
      anemia, jaundice, and progressive iron-overload. CDA1 is inherited in an
      autosomal recessive manner, with biallelic pathogenic variants in CDAN1 or
      C15orf41. This case report documents a severe fetal presentation of CDA1 where we
      identified two novel compound heterozygous mutations in CDAN1 and describes the
      associated pathologic findings and levels of iron-regulatory proteins hepcidin,
      erythroferrone, and GDF15.

PMID- 29599086
TI  - Evaluation of Mycoplasma gallisepticum (MG) ts-304 vaccine as a live attenuated
      vaccine in turkeys.
AB  - Mycoplasma gallisepticum (MG) is an important pathogen of poultry worldwide that
      causes chronic respiratory disease (CRD) in chickens and infectious sinusitis in
      turkeys. Vaxsafe MG (strain ts-11) is a live attenuated temperature sensitive
      vaccine that has been proven to be effective in controlling CRD in chickens, but
      it is not efficacious in turkeys. The gapA gene, which encodes a mature
      cytadhesin protein with a molecular weight of approximately 105 kDa, is not
      expressed in strain ts-11 because a 20 base pair reiterated sequence introduces a
      frame shift and causes premature truncation of the translated peptide. A GapA
      positive clone, MG ts-304, isolated from strain ts-11 has been shown to have
      enhanced efficacy in chickens. Here we describe studies we conducted to assess
      the safety and efficacy of the MG ts-304 vaccine candidate in turkeys. We found
      that MG ts-304 was able to colonise the trachea of 3-week-old turkeys and was
      safe, even at a tenfold overdose, inducing no adverse clinical signs of
      respiratory disease or significant gross lesions in the respiratory tract (air
      sacs or trachea), and was poorly transmissible to in-contact birds. We also
      showed that it was efficacious when administered to 3-week-old turkeys, inducing
      protective immunity against challenge with the M.gallisepticum wild-type strain
      Ap3AS. MG ts-304 is therefore a promising live attenuated vaccine candidate for
      use in turkeys.

PMID- 29599087
TI  - A novel method for strict intranasal delivery of non-replicating RSV vaccines in
      cotton rats and non-human primates.
AB  - Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis
      and pneumonia in children twelve months of age or younger and a significant cause
      of lower respiratory disease in older adults. As various clinical and preclinical
      candidates advance, cotton rats (Sigmodon hispidus) and non-human primates (NHP)
      continue to play a valuable role in RSV vaccine development, since both animals
      are semi-permissive to human RSV (HRSV). However, appropriate utilization of the
      models is critical to avoid mis-interpretation of the preclinical findings. Using
      a multimodality imaging approach; a fluorescence based optical imaging technique
      for the cotton rat and a nuclear medicine based positron emission tomography
      (PET) imaging technique for monkeys, we demonstrate that many common practices
      for intranasal immunization in both species result in inoculum delivery to the
      lower respiratory tract, which can result in poor translation of outcomes from
      the preclinical to the clinical setting. Using these technologies we define a
      method to limit the distribution of intranasally administered vaccines solely to
      the upper airway of each species, which includes volume restrictions in
      combination with injectable anesthesia. We show using our newly defined methods
      for strict intranasal immunization that these methods impact the immune responses
      and efficacy observed when compared to vaccination methods resulting in
      distribution to both the upper and lower respiratory tracts. These data emphasize
      the importance of well-characterized immunization methods in the preclinical
      assessment of intranasally delivered vaccine candidates.

PMID- 29599088
TI  - A single vaccination with non-replicating MVA at birth induces both immediate and
      long-term protective immune responses.
AB  - Newborns are considered difficult to protect against infections shortly after
      birth, due to their ineffective immune system that shows quantitative and
      qualitative differences compared to adults. However, here we show that a single
      vaccination of mice at birth with a replication-deficient live vaccine Modified
      Vaccinia Ankara [MVA] efficiently induces antigen-specific B- and T-cells that
      fully protect against a lethal Ectromelia virus challenge. Protection was induced
      within 2 weeks and using genetically modified mice we show that this protection
      was mainly T-cell dependent. Persisting immunological T-cell memory and
      neutralizing antibodies were obtained with the single vaccination. Thus, MVA
      administered as early as at birth induced immediate and long-term protection
      against an otherwise fatal disease and appears attractive as a new generation
      smallpox vaccine that is effective also in children. Moreover, it may have the
      potential to serve as platform for childhood vaccines as indicated by measles
      specific T- and B-cell responses induced in newborn mice vaccinated with
      recombinant MVA expressing measles antigens.

PMID- 29599089
TI  - Cancer-salient messaging for Human Papillomavirus vaccine uptake: A randomized
      controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Vaccination with Human Papillomavirus (HPV) vaccine is
      recommended for 11-12 years-old, but uptake is suboptimal. Current messaging
      focuses on HPV infection transmission and prevention. Parents and providers are
      often uncomfortable discussing sexual practices of adolescents, contributing to
      the delay/refusal of vaccine. We created a cervical cancer-salient message
      encouraging HPV vaccination, emphasizing disease salience and disease threat,
      while promoting self-efficacy. We hypothesized this message would have greater
      effects on vaccine confidence and intent to vaccinate compared to Centers for
      Disease Control and Prevention (CDC) and non-vaccine control messages. METHODS: A
      3-arm randomized trial was conducted. Parents of girls aged 9-17 were eligible
      for the study. We measured participants' vaccine confidence and intent to
      vaccinate at baseline and post intervention message. Recruitment and surveys were
      administered online through Amazon Mechanical Turk. RESULTS: 762 participants
      completed both surveys. We saw modest increases in vaccine confidence when
      comparing cervical cancer arm and control arm, and CDC arm and control arm;
      estimates were not statistically significant. The odds of reporting intent to
      vaccinate among the cervical cancer message arm were 1.13 times the odds of
      reporting intent to vaccinate in the control arm (95% CI: 0.30. 4.29). Intent to
      vaccinate was also not statistically significantly different between CDC message
      arm and control arm (OR = 1.25, 95%CI: 0.66, 2.37). CONCLUSION: Neither message
      had effect on intent to vaccinate, highlighting need for research to identify
      successful messaging strategies for HPV. Exploratory analyses suggest among
      parents with 'Low' vaccine confidence at baseline, the cervical cancer framed
      message may be more effective in changing intention than the CDC message or non
      vaccine control. Future work should target groups with 'Low' or 'Medium' vaccine
      confidence at baseline - they may be more amenable to change, and more receptive
      to disease-salient messaging. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov,
      Reference #: NCT03002324.

PMID- 29599090
TI  - Intranasal but not subcutaneous vaccination with LaAg allows rapid expansion of
      protective immunity against cutaneous leishmaniasis.
AB  - Mucosal but not parenteral vaccination with whole Leishmania amazonensis
      promastigotes antigens (LaAg) is known to increase host resistance to infection
      by an as yet unknown immune mechanism. Since early immune responses are critical
      for infection establishment, in the present study the differential responses
      elicited by subcutaneous (s.c.) and intranasal (i.n.) vaccination with LaAg were
      investigated during the initial stages of infection. For that, BALB/c mice were
      given two LaAg doses by i.n. or s.c. route prior to L. amazonensis infection in
      the footpad. It was found that mucosal vaccination prevented both T helper (Th) 2
      associated cutaneous hypersensitivity and local interleukin (IL)-4 production in
      the first days after parasite challenge in the footpad. That was accompanied by
      increased Th1 (T-bet and IL-12) and Treg (Foxp3 and IL-10) transcription factor
      and cytokine expression in the lesion draining lymph nodes. In contrast, s.c.
      LaAg predominantly led to higher Th2 (GATA3) and transforming growth factor (TGF)
      beta expression. Prior i.n. vaccination was able to prevent the disease
      exacerbating effect of s.c. vaccination. Although both CD4+ and CD8+ T cells were
      transiently increased in the cervical lymph nodes (cLN), the numbers of
      CD4+Foxp3+ regulatory T (Treg) cells decreased within 48 h of i.n. vaccination as
      compared to non-vaccinated mice. Adoptive transfer of such cLN cells conferred
      increased resistance to infected mice, mimicking the effect of i.n. vaccination.
      Altogether, these data indicate that i.n. vaccination with LaAg may prevent early
      peripheral expansion of detrimental cells normally elicited by active infection
      or s.c. vaccination, thus allowing full expansion of protective responses.

PMID- 29599091
TI  - Waist-height ratio in children of 7 to 11 years with high weight at birth and its
      relationship with gender, age and diet.
AB  - INTRODUCTION: Obesity (OB), considered as one of the Non-Transmissible Chronic
      Diseases, has as its fundamental characteristics that of being prevalent at a
      global level, increasing in number, affecting developed and developing countries,
      affecting both genders, and all ages and social groups. OBJECTIVE: To identify if
      high birth weight is a predictive factor (risk factor) for abdominal obesity in
      children 7 to 11 years old, and its relationship to gender, age and diet. METHOD:
      A case-control descriptive study was carried out with children born between
      January 1992 and December 1995, in order to identify early risk factors
      (atherosclerotic accelerators) such as abdominal obesity in children aged 7 to
      11, and who have a history of macrosomia or high birth weight, as well as their
      relationship with gender, age and diet. RESULTS: It was observed that the
      waist/height value was normal in 60.8% of the study group and in 64.00% in the
      control group. The difference between groups, gender, and age was not significant
      (P=.6859). As regards the diet in the study group (macrosomic), there was no
      significant association between the type of diet and waist circumference/height
      values, with an chi2=0.223 and P=.6373 (not significant). In the control group
      (with normal weight at birth), it was found that there is a significant
      statistical association between the type of diet and waist circumference/height
      values. This means that it can be stated, with 95% reliability, that the type of
      diet is associated with waist/height values. CONCLUSIONS: High birth weight is
      not a predictive factor (risk factor) for abdominal obesity (increased
      waist/height index). Gender and age are independent for abdominal obesity
      (macrosomic and normal weight at birth). The diet in high birth weight children
      is not related to the index waist-height index, which is not the case in those
      born with normal weight under the same conditions. The marked increase in
      abdominal obesity (Waist/height index) in children between 7 and 11 years old in
      both groups is worrying.

PMID- 29599092
TI  - Cardiorenal syndrome as predictor of in-hospital mortality in ST-segment
      elevation myocardial infarction.
AB  - INTRODUCTION: Cardiorenal syndrome includes numerous conditions affecting the
      heart and kidney, and is a strong predictor of cardiovascular mortality. METHOD:
      An analysis was performed on 157 consecutive patients admitted to the Coronary
      Care Unit of the Camilo Cienfuegos Hospital due to an ST-segment elevation
      myocardial infarction and heart failure, from January 2013 to December 2016. An
      analysis was made of the presence of cardiorenal syndrome and its relationship
      with epidemiological, clinical, and analytical variables, as well as
      complementary explorations. The relationship between cardiorenal syndrome and in
      hospital mortality was assessed using binary logistical regression. RESULTS: A
      total of 52 (33.1%) patients had a cardiorenal syndrome. The haemoglobin level
      was lower in the group of patients with cardiorenal syndrome (117.2 +/- 15.3 vs.
      123.3 +/- 15.1, P = .019), and in left ventricular ejection fraction (34.8 +/- 8
      vs. 43.2 +/- 10.8). A positive correlation was found between the Killip class and
      the increase in serum creatinine after 48 h. The serum creatinine was associated
      with left ventricular ejection fraction (r = 0.166; P = .038). The multivariate
      analysis showed that cardiorenal syndrome was an independent predictor of in
      hospital mortality when adjusted for a history of ischaemic heart disease,
      diabetes mellitus status, atrial fibrillation, ventricular arrhythmias, left
      ventricular ejection fraction, age and systolic blood pressure. CONCLUSIONS: The
      presence of cardiorenal syndrome has an influence on the prognosis of patients
      who suffer a cardiorenal syndrome. Its detection could be useful in the risk
      stratification.

PMID- 29599093
TI  - Aberrant within- and between-network connectivity of the mirror neuron system
      network and the mentalizing network in first episode psychosis.
AB  - INTRODUCTION: It has been suggested that the mentalizing network and the mirror
      neuron system network support important social cognitive processes that are
      impaired in schizophrenia. However, the integrity and interaction of these two
      networks have not been sufficiently studied, and their effects on social
      cognition in schizophrenia remain unclear. METHODS: Our study included 26 first
      episode psychosis (FEP) patients and 26 healthy controls. We utilized resting
      state functional connectivity to examine the a priori-defined mirror neuron
      system network and the mentalizing network and to assess the within- and between
      network connectivities of the networks in FEP patients. We also assessed the
      correlation between resting-state functional connectivity measures and theory of
      mind performance. RESULTS: FEP patients showed altered within-network
      connectivity of the mirror neuron system network, and aberrant between-network
      connectivity between the mirror neuron system network and the mentalizing
      network. The within-network connectivity of the mirror neuron system network was
      noticeably correlated with theory of mind task performance in FEP patients.
      CONCLUSION: The integrity and interaction of the mirror neuron system network and
      the mentalizing network may be altered during the early stages of psychosis.
      Additionally, this study suggests that alterations in the integrity of the mirror
      neuron system network are highly related to deficient theory of mind in
      schizophrenia, and this problem would be present from the early stage of
      psychosis.

PMID- 29599094
TI  - Replication of GWAS identified miR-137 and its target gene polymorphisms in
      Schizophrenia of South Indian population and meta-analysis with Psychiatric
      Genomics Consortium.
AB  - Schizophrenia is a complex psychiatric disorder involving multiple genes each
      contributing a small risk. Genome-wide association studies (GWASs) have
      identified hundreds of risk loci for schizophrenia including miR-137, a miRNA
      shown to be involved in neuronal development. Several genes regulated by miR-137
      were also reported as top risk genes associated with schizophrenia and has been
      hypothesised that the dysregulation of miR-137 and its target could be involved
      in the aetiology of schizophrenia. Here, we replicated the four European GWAS
      hits, miR-137-rs1625579 and three of its validated target gene loci SNPs (ZNF804a
      rs1344706, CACNA1C-rs4765905 and TCF4-rs9960767) by genotyping in 2074 samples
      (schizophrenia cases-1005; controls-1069) from South Indian Population. In this
      study, only the CACNA1C rs4765905 showed a significant association (OR=1.24,
      p=0.006). Three SNPs (rs1625579, rs1344706 and rs4765905) showed a consistent
      direction of effect with previous studies and the polygenic risk score
      constructed using the weighted sum of these three SNPs showed a significant
      association with Schizophrenia in this population (OR=3.78, p=0.005). Further, we
      carried out meta-analysis combining our results with the Psychiatric Genomics
      Consortium (PGC2) data and observed a considerable increase in GWAS significance.

PMID- 29599095
TI  - Reported Resuscitation of a Hypothermic Avalanche Victim With Assisted
      Ventilation in 1939.
AB  - We present a historical case of a 12-year-old boy who survived a reported
      avalanche burial in 1939 in the Upper Peninsula of Michigan. The boy was
      completely buried for at least 3 h, head down, at a depth of about 1 m. He was
      extricated without signs of life and likely hypothermic by his father, who took
      him to his home. There, the father performed assisted ventilation for 3 hours
      using the Schafer method, a historical method of artificial ventilation, without
      any specific rewarming efforts. The boy recovered neurologically intact. This
      case illustrates the importance of attempting resuscitation, possibly prolonged,
      of victims of hypothermia, even those who are apparently dead.

PMID- 29599096
TI  - 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.
AB  - BACKGROUND: Antithrombotic therapy with oral anticoagulants (OAC) in patients
      with atrial fibrillation (AF) after stent implantation, where dual antiplatelet
      therapy (DAPT) is also recommended, is not established. Antithrombotic therapies
      prescribed vary widely among cardiologists and may change year by year, according
      to the accumulation of new evidence. METHODS: A questionnaire-based survey
      concerning the antithrombotic therapy prescribed for OAC-treated AF patients who
      underwent stent implantation was conducted from 2014 to 2016. The survey was
      completed by the Fellows of the Japanese College of Cardiology (FJCC). RESULTS:
      The questionnaire was sent to 1023 fellows in 2014, a total of 1057 fellows in
      2015, and 1073 fellows in 2016; 268 (26%), 418 (40%), and 416 (39%) answers were
      obtained, respectively. The duration of DAPT did not change in patients with bare
      metal stents; however, it tended to become shorter with the use of the drug
      eluting stent (DES). Significant shortening of DAPT duration was observed with
      DES for stable coronary artery disease from 2015 to 2016. A similar tendency was
      observed for acute coronary syndrome (ACS); however, this was not significant
      between 2015 and 2016. A shorter duration of DAPT is preferred by
      electrophysiologists rather than by interventionalists and general cardiologists.
      OAC monotherapy is not popular one year after stent implantation, although the
      prevalence of its use increased year by year. Aspirin and thienopyridines are
      used equally as a single antiplatelet in DAPT, and clopidogrel is also a popular
      agent. The prevalence of direct OAC use increased year by year. CONCLUSIONS: The
      questionnaire showed variation in antithrombotic therapy used for OAC-treated AF
      patients after stenting, and how it changes year by year. Although the duration
      of DAPT tended to shorten, variations are still observed, i.e. the selection of a
      single antiplatelet or OAC.

PMID- 29599097
TI  - High-sensitivity cardiac troponin T and prognosis in patients with ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: Evidence on the use of high-sensitivity cardiac troponins (hs-cTn) to
      risk-stratify patients with ST-segment elevation myocardial infarction (STEMI) is
      limited. METHODS: We assessed the prognostic value of preprocedural (admission)
      and peak postprocedural hs-cTnT in 818 patients with STEMI treated with primary
      percutaneous coronary intervention (PPCI). Preprocedural and peak postprocedural
      hs-cTnT was measured. The primary outcome was 3-year all-cause mortality.
      RESULTS: The median values of preprocedural and peak postprocedural hs-cTnT were
      153ng/L and 1980ng/L. Overall, 134 patients died during the follow-up. There were
      85 deaths in patients with preprocedural hs-cTnT >median value and 49 deaths in
      patients with preprocedural hs-cTnT <=median value [Kaplan-Meier estimates of
      mortality, 22.2% and 13.5%; unadjusted hazard ratio (HR)=1.88, 95% confidence
      interval (CI) 1.32-2.67, p<0.001]. According to peak postprocedural hs-cTnT,
      there were 84 deaths in patients with postprocedural hs-cTnT >median value and 50
      deaths in patients with postprocedural hs-cTnT <=median value [Kaplan-Meier
      estimates of mortality, 22.3% and 13.4%; unadjusted HR=1.82 (1.28-2.59),
      p<0.001]. After adjustment, preprocedural [adjusted HR=1.08 (1.03-1.12), p<0.001]
      and peak postprocedural hs-cTnT value [adjusted HR=1.06 (1.04-1.08), p<0.001]
      were independently associated with 3-year mortality (with risk estimates
      calculated per 70*99th upper reference limit of hs-cTnT). The C statistic of
      multivariable model increased from 0.868 (0.841-0.895) to 0.872 (0.845-0.898)
      after incorporation of preprocedural hs-cTnT (p=0.050) and to 0.874 (0.846-0.899)
      after incorporation of the postprocedural hs-cTnT into the model (p=0.035).
      CONCLUSIONS: In conclusion, admission or peak postprocedural hs-cTnT is
      independently associated with the risk for 3-year mortality in patients with
      STEMI undergoing PPCI.

PMID- 29599098
TI  - The Selvester QRS score as a predictor of cardiac events in nonischemic dilated
      cardiomyopathy.

PMID- 29599099
TI  - Predictive value of acute kidney injury for major adverse cardiovascular events
      following tricuspid annuloplasty: A comparison of three consensus criteria.
AB  - BACKGROUND: Tricuspid annuloplasty (TA) is increasingly being performed, but the
      clinical outcome is unsatisfactory. Acute kidney injury (AKI) is a common
      complication following cardiac surgery and predicts outcome. Nonetheless the
      occurrence rate and prognostic value of AKI after TA are unclear. METHODS: This
      study reviewed 339 consecutive patients (age 65+/-11 years; male 42%) who
      underwent TA. The incidence of AKI was defined according to
      risk/injury/failure/loss/end stage (RIFLE), acute kidney injury network (AKIN),
      and kidney disease improving global outcomes (KDIGO) criteria, respectively.
      Major adverse cardiovascular events (MACE) was defined as death, heart failure,
      stroke, and myocardial infarction (MI). The influence of AKI on MACE was
      evaluated as a short-term outcome and outcome beyond 30 days. RESULTS: The
      incidence of AKI, defined according to RIFLE, AKIN, and KDIGO was 57%, 52%, and
      53%, respectively. MACE occurred in 94 cases (21 deaths, 63 heart failure
      requiring hospitalization, 7 stroke, and 3 MI). For short-term outcome, AKI
      defined by all three scoring systems was independently associated with MACE and
      death (p<0.01 for both), but not heart failure, stroke, or MI. For outcome beyond
      30 days, AKI by all three criteria was associated with MACE and heart failure.
      Only AKI by AKIN and KDIGO, but not RIFLE, was independently associated with
      death. CONCLUSION: Our data suggest AKI affects over half of all patients who
      undergo TA, and has a major and long-lasting impact on survival, MACE, and heart
      failure. Use of AKIN and KDIGO is more useful than the RIFLE criteria when
      determining the prognostic value of AKI for mortality beyond 30 days.

PMID- 29599100
TI  - Sadness and beauty in art-Do they really coincide in the brain?: Comment on "An
      integrative review of the enjoyment of sadness associated with music" by Eerola
      et al.

PMID- 29599101
TI  - Corrigendum to "Immune-enhancing effects of polysaccharides extracted from Lilium
      lancifolium Thunb" [Int. Immunopharmacol. 52 (2017) 119-126].

PMID- 29599102
TI  - Assessment of dietary intake in Spanish university students of health sciences.
AB  - INTRODUCTION: Nutritional intake during early ages has been associated to disease
      onset later in life. This study aimed to assess dietary intake in Spanish
      university students of health sciences as compared to national recommended
      dietary intakes (DRIs). METHODS: A cross-sectional study was conducted including
      585 university students of health sciences aged 18-25 years. Dietary intake was
      assessed using a 72-h diet recall. A control group was selected from Spanish
      National Dietary Intake Survey (ENIDE) data. RESULTS: Intake of energy, protein,
      fat, fatty acids, and cholesterol was significantly lower (p<0.001) in university
      students compared to controls, while fiber intake showed the opposite trend
      (p<0.001). Total fat and carbohydrate intake was consistent with recommendations,
      but protein intake was lower than recommended. Intake of saturated fatty acids
      (SFAs) was markedly higher than nutrition goals, while intake of monounsaturated
      fatty acids (MUFAs) was lower. Both students and the reference control group did
      not reach the optimal dietary intake of iodine and vitamins D and E, while sodium
      intake was excessive in both groups. CONCLUSIONS: Dietary habits of university
      students were mainly characterized by low intakes of energy, protein, fats, fatty
      acids, and cholesterol, and high intake of fiber as compared to the general
      population. Intake of iodine and vitamins D and E was low, while sodium intake
      was excessive in both university students and the general population. Dietary
      interventions should be considered to prevent nutritional deficiencies and to
      ensure a balanced diet.

PMID- 29599103
TI  - Assessment of structural valve deterioration of transcatheter aortic
      bioprosthetic balloon-expandable valves using the new European consensus
      definition.
AB  - AIMS: Durability of transcatheter aortic bioprosthetic valves remains a major
      issue. Standardised definitions of deterioration and failure of bioprosthetic
      valves have recently been proposed. The aim of this study was to assess
      structural transcatheter valve deterioration (SVD) and bioprosthetic valve
      failure (BVF) using these new definitions. METHODS AND RESULTS: All TAVI patients
      implanted up to September 2012 with a minimal theoretical five-year follow-up
      were included. Systematic clinical and echocardiographic follow-up was performed
      annually. New standardised definitions were used to assess durability of
      transcatheter aortic bioprosthetic valves. From 2002 to 2012, 378 patients were
      included. Mean age and logistic EuroSCORE were 83.3+/-6.8 years and 22.8+/-13.1%.
      Thirty-day mortality was 13.2%. Nine patients had SVD including two severe forms
      and two patients had definite late BVF. The incidence of SVD and BVF at eight
      years was 3.2% (95% CI: 1.45-6.11) and 0.58% (95% CI: 0.15-2.75), respectively.
      CONCLUSIONS: Even though limited by the poor survival of the very high
      risk/compassionate early population, our data do not demonstrate any alarm
      concerning transcatheter aortic valve durability. Careful prospective assessment
      in younger and lower-risk patients and comparison with surgical bioprosthetic
      valves are required for further assessment of the long-term durability of
      transcatheter valves.

PMID- 29599104
TI  - Physical Trauma Patients with Symptoms of an Acute and Posttraumatic Stress
      Disorder: Protocol for an Observational Prospective Cohort Study.
AB  - BACKGROUND: Injury, medical treatment, and rehabilitation can have major impacts
      on patients' wellbeing. About 25-33% of the patients experience an acute stress
      disorder (ASD) or a posttraumatic stress disorder (PTSD) after injury. ASD is a
      relatively new diagnosis. Therefore, knowledge about patients' experiences, the
      course of ASD and PTSD, and who is at risk for developing ASD or PTSD is lacking.
      OBJECTIVE: The aims of this multi-method study are to explore patients'
      experiences with injury (and their care) using a focus group study. Then, in the
      observational study, different courses of ASD, PTSD, and quality of life will be
      examined. In addition, this study will examine if these courses could be
      characterized by socio-demographic, clinical, and psychological variables.
      Consequently, a risk profile will be developed to determine which patients are at
      risk for developing ASD or PTSD during the 12 months after injury. METHODS:
      Trauma patients treated in the shock room (in 2015) of the Elisabeth-TweeSteden
      Hospital will share their experiences with injury in the focus group study. Open,
      axial, and selective coding will be used to analyze the data. Concerning the
      observational study, patients treated in the shock room (during 2016 and 2017,
      Elisabeth-TweeSteden Hospital and Erasmus Medical Centre) will be asked to
      participate. The inclusion period is 12 months. Participants will complete the
      Impact of Event Scale-Revised, MINI-plus, the Hospital Anxiety and Depression
      Scale, and the World Health Organization Quality of Life-BREF after inclusion and
      at 3, 6, 9, and 12 months after injury. The NEO-Five Factor Inventory and the
      State-Trait Anxiety Inventory-Trait are completed after inclusion only. Repeated
      measures of latent class analysis and linear mixed models will be used to examine
      the research aims. RESULTS: This project was funded in August 2015 by ZonMw. The
      results of the focus group study are expected in the first trimester of 2018.
      With regard to the observational study, recruitment is currently underway. Data
      collection will be completed in November 2018. The first results will be expected
      in the first trimester of 2019. CONCLUSIONS: This is the first multi-method study
      in trauma patients that examines patients' experiences (qualitative design) as
      well as psychological disorders (observational prospective). This study will
      contribute to necessary information on psychological consequences after injury.
      Moreover, it provides knowledge about which patients to include in future
      psychological intervention research. Finally, awareness in clinicians about the
      psychological consequences can be created, so they are able to act more
      effectively to provide patient-oriented care. TRIAL REGISTRATION: Netherlands
      Trial Registry NTR6258;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6258 (Archived by
      WebCite at http://www.webcitation.org/6xSCiO1bS).

PMID- 29599105
TI  - Participants' Perceptions on the Use of Wearable Devices to Reduce Sitting Time:
      Qualitative Analysis.
AB  - BACKGROUND: Recent epidemiological evidence indicates that, on average, people
      are sedentary for approximately 7.7 hours per day. There are deleterious effects
      of prolonged sedentary behavior that are separate from participation in physical
      activity and include increased risk of weight gain, cancer, metabolic syndrome,
      diabetes, and heart disease. Previous trials have used wearable devices to
      increase physical activity in studies; however, additional research is needed to
      fully understand how this technology can be used to reduce sitting time.
      OBJECTIVE: The purpose of this study was to explore the potential of wearable
      devices as an intervention tool in a larger sedentary behavior study through a
      general inductive and deductive analysis of focus group discussions. METHODS: We
      conducted four focus groups with 15 participants to discuss 7 different wearable
      devices with sedentary behavior capabilities. Participants recruited for the
      focus groups had previously participated in a pilot intervention targeting
      sedentary behavior over a 3-week period and were knowledgeable about the
      challenges of reducing sitting time. During the focus groups, participants
      commented on the wearability, functionality, and feedback mechanism of each
      device and then identified their two favorite and two least favorite devices.
      Finally, participants designed and described their ideal or dream wearable
      device. Two researchers, who have expertise analyzing qualitative data, coded and
      analyzed the data from the focus groups. A thematic analysis approach using
      Dedoose software (SocioCultural Research Consultants, LLC version 7.5.9) guided
      the organization of themes that reflected participants' perspectives. RESULTS:
      Analysis resulted in 14 codes that we grouped into themes. Three themes emerged
      from our data: (1) features of the device, (2) data the device collected, and (3)
      how data are displayed. CONCLUSIONS: Current wearable devices for increasing
      physical activity are insufficient to intervene on sitting time. This was
      especially evident when participants voted, as several participants reported
      using a "process of elimination" as opposed to choosing favorites because none of
      the devices were ideal for reducing sitting time. To overcome the limitations in
      current devices, future wearable devices designed to reduce sitting time should
      include the following features: waterproof, long battery life, accuracy in
      measuring sitting time, real time feedback on progress toward sitting reduction
      goals, and flexible options for prompts to take breaks from sitting.

PMID- 29599106
TI  - A Web- and Mobile-Based Map of Mental Health Resources for Postsecondary Students
      (Thought Spot): Protocol for an Economic Evaluation.
AB  - BACKGROUND: Youth demonstrate a low propensity to seek help for mental health
      issues and exhibit low use of health services despite the high prevalence of
      mental health challenges in this population. Research has found that delivering
      interventions via the internet and mobile devices is an effective way to reach
      youth. Thought Spot, a Web- and mobile-based map, was developed to help
      transition-aged youth in postsecondary settings overcome barriers to help
      seeking, thereby reducing the economic burden associated with untreated mental
      health issues. OBJECTIVE: This paper presents the protocol for an economic
      evaluation that will be conducted in conjunction with a randomized controlled
      trial (RCT) to evaluate the effectiveness and cost of Thought Spot compared with
      usual care in terms of self-efficacy for mental health help-seeking among
      postsecondary students. METHODS: A partially blinded RCT will be conducted to
      assess the impact of Thought Spot on the self-efficacy of students for mental
      health help-seeking. Students from 3 postsecondary institutions in Ontario,
      Canada will be randomly allocated to 1 of 2 intervention groups (resource
      pamphlet or Thought Spot) for 6 months. The economic evaluation will focus on the
      perspective of postsecondary institutions or other organizations interested in
      using Thought Spot. Costs and resources for operating and maintaining the
      platform will be reported and compared with the costs and resource needs
      associated with usual care. The primary outcome will be change in help-seeking
      intentions, measured using the General Help-Seeking Questionnaire. The cost
      effectiveness of the intervention will be determined by calculating the
      incremental cost-effectiveness ratio, which will then be compared with
      willingness to pay. RESULTS: The RCT is scheduled to begin in February 2018 and
      will run for 6 months, after which the economic evaluation will be completed.
      CONCLUSIONS: We expect to demonstrate that Thought Spot is a cost-effective way
      to improve help-seeking intentions and encourage help-seeking behavior among
      postsecondary students. The findings of this study will help inform postsecondary
      institutions when they are allocating resources for mental health initiatives.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT03412461;
      https://clinicaltrials.gov/ct2/show/NCT03412461 (Archived at WebCite at
      http://www.webcitation.org/6xy5lWpnZ).

PMID- 29599107
TI  - Growth Dynamics of Patient-Provider Internet Communication: Trend Analysis Using
      the Health Information National Trends Survey (2003 to 2013).
AB  - BACKGROUND: Communication is key in chronic disease management, and the internet
      has altered the manner in which patients and providers can exchange information.
      Adoption of secure messaging differs among patients due to the digital divide
      that keeps some populations from having effective access to online resources.
      OBJECTIVE: This study aimed to examine the current state of online patient
      provider communication, exploring trends over time in the use of online patient
      provider communication tools. METHODS: A 3-part analytic process was used to
      study the following: (1) reanalysis, (2) close replication across years, and (3)
      trend analysis extension. During the reanalysis stage, the publicly available
      Health Information National Trends Survey (HINTS) 1 and 2 data were used with the
      goal of identifying the precise analytic methodology used in a prior study,
      published in 2007. The original analysis was extended to add 3 additional data
      years (ie, 2008, 2011, and 2013) using the original analytical approach with the
      purpose of identifying trends over time. Multivariate logistic regression was
      used to analyze pooled data across all years, with year as an added predictor, in
      addition to a model for each individual data year. RESULTS: The odds of internet
      users to communicate online with health care providers was significantly and
      increasingly higher year-over-year, starting in 2003 (2005: odds ratio [OR] 1.31,
      95% CI 1.03-1.68; 2008: OR 2.14, 95% CI 1.76-2.59; 2011: OR 2.92, 95% CI 2.33
      3.66; and 2013: OR 5.77; 95% CI 4.62-7.20). Statistically significant socio
      economic factors found to be associated with internet users communicating online
      with providers included age, having health insurance, having a history of cancer,
      and living in an urban area of residence. CONCLUSIONS: The proportion of internet
      users communicating online with their health care providers has significantly
      increased since 2003. Although these trends are encouraging, access challenges
      still exist for some groups, potentially giving rise to a new set of health
      disparities related to communication.

PMID- 29599108
TI  - Lessons Learned From a Living Lab on the Broad Adoption of eHealth in Primary
      Health Care.
AB  - BACKGROUND: Electronic health (eHealth) solutions are considered to relieve
      current and future pressure on the sustainability of primary health care systems.
      However, evidence of the effectiveness of eHealth in daily practice is missing.
      Furthermore, eHealth solutions are often not implemented structurally after a
      pilot phase, even if successful during this phase. Although many studies on
      barriers and facilitators were published in recent years, eHealth implementation
      still progresses only slowly. To further unravel the slow implementation process
      in primary health care and accelerate the implementation of eHealth, a 3-year
      Living Lab project was set up. In the Living Lab, called eLabEL, patients, health
      care professionals, small- and medium-sized enterprises (SMEs), and research
      institutes collaborated to select and integrate fully mature eHealth technologies
      for implementation in primary health care. Seven primary health care centers, 10
      SMEs, and 4 research institutes participated. OBJECTIVE: This viewpoint paper
      aims to show the process of adoption of eHealth in primary care from the
      perspective of different stakeholders in a qualitative way. We provide a real
      world view on how such a process occurs, including successes and failures related
      to the different perspectives. METHODS: Reflective and process-based notes from
      all meetings of the project partners, interview data, and data of focus groups
      were analyzed systematically using four theoretical models to study the adoption
      of eHealth in primary care. RESULTS: The results showed that large-scale
      implementation of eHealth depends on the efforts of and interaction and
      collaboration among 4 groups of stakeholders: patients, health care
      professionals, SMEs, and those responsible for health care policy (health care
      insurers and policy makers). These stakeholders are all acting within their own
      contexts and with their own values and expectations. We experienced that patients
      reported expected benefits regarding the use of eHealth for self-management
      purposes, and health care professionals stressed the potential benefits of
      eHealth and were interested in using eHealth to distinguish themselves from other
      care organizations. In addition, eHealth entrepreneurs valued the collaboration
      among SMEs as they were not big enough to enter the health care market on their
      own and valued the collaboration with research institutes. Furthermore, health
      care insurers and policy makers shared the ambition and need for the development
      and implementation of an integrated eHealth infrastructure. CONCLUSIONS: For
      optimal and sustainable use of eHealth, patients should be actively involved,
      primary health care professionals need to be reinforced in their management,
      entrepreneurs should work closely with health care professionals and patients,
      and the government needs to focus on new health care models stimulating
      innovations. Only when all these parties act together, starting in local
      communities with a small range of eHealth tools, the potential of eHealth will be
      enforced.

PMID- 29599109
TI  - Does Eating Chicken Feet With Pickled Peppers Cause Avian Influenza?
      Observational Case Study on Chinese Social Media During the Avian Influenza A
      (H7N9) Outbreak.
AB  - BACKGROUND: A hot topic on the relationship between a popular avian-origin food
      and avian influenza occurred on social media during the outbreak of the emerging
      avian influenza A (H7N9). The misinformation generated from this topic had caused
      great confusion and public concern. OBJECTIVE: Our goals were to analyze the
      trend and contents of the relevant posts during the outbreak. We also aimed to
      understand the characteristics of the misinformation and to provide suggestions
      to reduce public misconception on social media during the emerging disease
      outbreak. METHODS: The original microblog posts were collected from China's Sina
      Weibo and Tencent Weibo using a combination of keywords between April 1, 2013 and
      June 2, 2013. We analyzed the weekly and daily trend of the relevant posts.
      Content analyses were applied to categorize the posts into 4 types with unified
      sorting criteria. The posts' characteristics and geographic locations were also
      analyzed in each category. We conducted further analysis on the top 5 most
      popular misleading posts. RESULTS: A total of 1680 original microblog posts on
      the topic were retrieved and 341 (20.30%) of these posts were categorized as
      misleading messages. The number of relevant posts had not increased much during
      the first 2 weeks but rose to a high level in the next 2 weeks after the sudden
      increase in number of reported cases at the beginning of week 3. The posts under
      "misleading messages" occurred and increased from the beginning of week 3, but
      their daily posting number decreased when the daily number of posts under
      "refuting messages" outnumbered them. The microbloggers of the misleading posts
      had the lowest mean rank of followers and previous posts, but their posts had a
      highest mean rank of posts. The proportion of "misleading messages" in places
      with no reported cases was significantly higher than that in the epidemic areas
      (23.6% vs 13.8%). The popular misleading posts appeared to be short and consisted
      of personal narratives, which were easily disseminated on social media.
      CONCLUSIONS: Our findings suggested the importance of responding to common
      questions and misconceptions on social media platforms from the beginning of
      disease outbreaks. Authorities need to release clear and reliable information
      related to the popular topics early on. The microbloggers posting correct
      information should be empowered and their posts could be promoted to clarify
      false information. Equal importance should be attached to clarify misinformation
      in both the outbreak and nonoutbreak areas.

PMID- 29599110
TI  - Long-term evaluation of physical improvement and survival of autologous stem cell
      transplantation in POEMS syndrome.

PMID- 29599111
TI  - Absence of a quick fix does not mean 'do nothing:' time to address drug use in
      the ED.

PMID- 29599112
TI  - Clinical Monitoring of Well-Appearing Infants Born to Mothers With
      Chorioamnionitis.
AB  - BACKGROUND: The risk of early-onset sepsis is low in well-appearing late-preterm
      and term infants even in the setting of chorioamnionitis. The empirical
      antibiotic strategies for chorioamnionitis-exposed infants that are recommended
      by national guidelines result in antibiotic exposure for numerous well-appearing,
      uninfected infants. We aimed to reduce unnecessary antibiotic use in
      chorioamnionitis-exposed infants through the implementation of a treatment
      approach that focused on clinical presentation to determine the need for
      antibiotics. METHODS: Within a quality-improvement framework, a new treatment
      approach was implemented in March 2015. Well-appearing late-preterm and term
      infants who were exposed to chorioamnionitis were clinically monitored for at
      least 24 hours in a level II nursery; those who remained well appearing received
      no laboratory testing or antibiotics and were transferred to the level I nursery
      or discharged from the hospital. Newborns who became symptomatic were further
      evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing,
      culture results, and clinical outcomes were collected. RESULTS: Among 277 well
      appearing, chorioamnionitis-exposed infants, 32 (11.6%) received antibiotics
      during the first 15 months of the quality-improvement initiative. No cases of
      culture result-positive early-onset sepsis occurred. No infant required
      intubation or inotropic support. Only 48 of 277 (17%) patients had sepsis
      laboratory testing. The implementation of the new approach was associated with a
      55% reduction (95% confidence interval 40%-65%) in antibiotic exposure across all
      infants >=34 weeks' gestation born at our hospital. CONCLUSIONS: A management
      approach using clinical presentation to determine the need for antibiotics in
      chorioamnionitis-exposed infants was successful in reducing antibiotic exposure
      and was not associated with any clinically relevant delays in care or adverse
      outcomes.

PMID- 29599114
TI  - We should embrace WhatsApp and try to mitigate concerns.

PMID- 29599113
TI  - Vomiting With Head Trauma and Risk of Traumatic Brain Injury.
AB  - OBJECTIVES: To determine the prevalence of traumatic brain injuries in children
      who vomit after head injury and identify variables from published clinical
      decision rules (CDRs) that predict increased risk. METHODS: Secondary analysis of
      the Australasian Paediatric Head Injury Rule Study. Vomiting characteristics were
      assessed and correlated with CDR predictors and the presence of clinically
      important traumatic brain injury (ciTBI) or traumatic brain injury on computed
      tomography (TBI-CT). Isolated vomiting was defined as vomiting without other CDR
      predictors. RESULTS: Of the 19 920 children enrolled, 3389 (17.0%) had any
      vomiting, with 2446 (72.2%) >2 years of age. In 172 patients with ciTBI, 76 had
      vomiting (44.2%; 95% confidence interval [CI] 36.9%-51.7%), and in 285 with TBI
      CT, 123 had vomiting (43.2%; 95% CI 37.5%-49.0%). With isolated vomiting, only 1
      (0.3%; 95% CI 0.0%-0.9%) had ciTBI and 2 (0.6%; 95% CI 0.0%-1.4%) had TBI-CT.
      Predictors of increased risk of ciTBI with vomiting by using multivariate
      regression were as follows: signs of skull fracture (odds ratio [OR] 80.1; 95% CI
      43.4-148.0), altered mental status (OR 2.4; 95% CI 1.0-5.5), headache (OR 2.3;
      95% CI 1.3-4.1), and acting abnormally (OR 1.86; 95% CI 1.0-3.4). Additional
      features predicting TBI-CT were as follows: skull fracture (OR 112.96; 95% CI
      66.76-191.14), nonaccidental injury concern (OR 6.75; 95% CI 1.54-29.69),
      headache (OR 2.55; 95% CI 1.52-4.27), and acting abnormally (OR 1.83; 95% CI 1.10
      3.06). CONCLUSIONS: TBI-CT and ciTBI are uncommon in children presenting with
      head injury with isolated vomiting, and a management strategy of observation
      without immediate computed tomography appears appropriate.

PMID- 29599116
TI  - Impact of processing technique on bronchoalveolar lavage cellular analysis.

PMID- 29599117
TI  - Risk assessment in pulmonary arterial hypertension.

PMID- 29599115
TI  - The UPRmt Protects Caenorhabditis elegans from Mitochondrial Dysfunction by
      Upregulating Specific Enzymes of the Mevalonate Pathway.
AB  - The mevalonate pathway is the primary target of the cholesterol-lowering drugs
      statins, some of the most widely prescribed medicines of all time. The pathway's
      enzymes not only catalyze the synthesis of cholesterol but also of diverse
      metabolites such as mitochondrial electron carriers and isoprenyls. Recently, it
      has been shown that one type of mitochondrial stress response, the UPRmt, can
      protect yeast, Caenorhabditis elegans, and cultured human cells from the
      deleterious effects of mevalonate pathway inhibition by statins. The mechanistic
      basis for this protection, however, remains unknown. Using C. elegans, we found
      that the UPRmt does not directly affect the levels of the statin target HMG-CoA
      reductase, the rate-controlling enzyme of the mevalonate pathway in mammals.
      Instead, in C. elegans the UPRmt upregulates the first dedicated enzyme of the
      pathway, HMG-CoA synthase (HMGS-1). A targeted RNA interference (RNAi) screen
      identified two UPRmt transcription factors, ATFS-1 and DVE-1, as regulators of
      HMGS-1 A comprehensive analysis of the pathway's enzymes found that, in addition
      to HMGS-1, the UPRmt upregulates enzymes involved with the biosynthesis of
      electron carriers and geranylgeranylation intermediates. Geranylgeranylation, in
      turn, is requisite for the full execution of the UPRmt 3response. Thus, the UPRmt
      acts in at least three coordinated, compensatory arms to upregulate specific
      branches of the mevalonate pathway, thereby alleviating mitochondrial stress. We
      propose that statin-mediated inhibition of the mevalonate pathway blocks this
      compensatory system of the UPRmt and consequentially impedes mitochondrial
      homeostasis. This effect is likely one of the principal bases for the adverse
      side effects of statins.

PMID- 29599118
TI  - Risk assessment in pulmonary arterial hypertension.

PMID- 29599119
TI  - The lower limit of normal versus a fixed ratio to assess airflow limitation: will
      the debate ever end?

PMID- 29599120
TI  - Tackling vehicle emissions and physical inactivity. Scottish Government doubles
      active travel budget.

PMID- 29599121
TI  - 'What's my risk of sustaining an ACL injury while playing football (soccer)?' A
      systematic review with meta-analysis.
AB  - OBJECTIVE: To estimate the incidence proportion (IP) and incidence rate (IR) of
      ACL injury in football players. DESIGN: Systematic review with meta-analysis.
      DATA SOURCES: PubMed, CINAHL and SPORTDiscus electronic databases were searched
      from inception to 20 January 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDY:
      Studies that reported the total number of participants/population by sex, total
      number of ACL injuries by sex and total person-time by sex were included.
      RESULTS: Twenty-eight studies were included. The IP and IR of ACL injury in
      female football players were 2.0% (95% CI 1.2% to 3.1%) and 2.0/10 000 athlete
      exposures (AEs) (95% CI 1.6 to 2.6; I2=91%) over a period of one season to 4
      years. The IP and IR of ACL injury in male players were 3.5% (95% CI 0.7% to
      8.2%) and 0.9/10 000 AEs (95% CI 0.7 to 1.1; I2=94%). Studies that evaluated
      matched cohorts of female and male players showed no difference in IP (relative
      risk=1.2; 95% CI 0.9 to 1.6; P=0.47) over a period of one season to 4 years.
      Women were at greater risk than men (incidence rate ratio (IRR)=2.2; 95% CI 1.6
      to 3.1; I2=83%; P<0.001). When accounting for participation level, the difference
      in IR between women and men was greatest for intermediate players (IRR=2.9; 95%
      CI 2.4 to 3.6) compared with amateur (IRR=2.6; 95% CI 1.4 to 4.8) and elite
      (IRR=2.0; 95% CI 1.1 to 3.4) players. SUMMARY/CONCLUSION: Overall, more men
      sustained ACL injury in football. There was no difference in the relative risk of
      ACL injury between female and male football players in a window that spanned one
      season to 4 years. The IR of ACL injury among women was 2.2 times higher than the
      IR of ACL injury among men. The reported sex disparity in ACL injury was
      independent of participation level.

PMID- 29599122
TI  - Intersectin goes nuclear: secret life of an endocytic protein.
AB  - Intersectin 1-short (ITSN1-s) is a 1220 amino acid ubiquitously expressed
      scaffold protein presenting a multidomain structure that allows to
      spatiotemporally regulate the functional interaction of a plethora of proteins.
      Besides its well-established role in endocytosis, ITSN1-s is involved in the
      regulation of cell signaling and is implicated in tumorigenesis processes,
      although the signaling pathways involved are still poorly understood. Here, we
      identify ITSN1-s as a nucleocytoplasmic trafficking protein. We show that, by
      binding to importin (IMP)alpha, a small fraction of ITSN1-s localizes in the cell
      nucleus at the steady state, where it preferentially associates with the nuclear
      envelope and interacts with lamin A/C. However, upon pharmacological ablation of
      chromosome region maintenance 1 (CRM-1)-dependent nuclear export pathway, the
      protein accumulates into the nucleus, thus revealing its moonlighting nature.
      Analysis of deletion mutants revealed that the coiled coil (CC) and Src homology
      (SH3) regions play the major role in its nucleocytoplasmic shuttling. While no
      evidence of nuclear localization signal (NLS) was detected in the CC region, a
      functional bipartite NLS was identified within the SH3D region of ITSN1-s
      (RKKNPGGWWEGELQARGKKRQIGW-1127), capable of conferring energy-dependent nuclear
      accumulation to reporter proteins and whose mutational ablation affects nuclear
      import of the whole SH3 region. Thus, ITSN1-s is an endocytic protein, which
      shuttles between the nucleus and the cytoplasm in a CRM-1- and IMPalpha-dependent
      fashion.

PMID- 29599123
TI  - Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in
      pancreatic NETs.
AB  - Pancreatic neuroendocrine tumors (PanNETs) have considerable malignant potential.
      Frequent somatic mutations and loss of DAXX protein expression have been found in
      PanNETs. DAXX is known as a transcriptional repressor; however, molecular
      functions underlying DAXX loss remain unclear in PanNETs. We evaluated DAXX
      expression by immunohistochemistry in 44 PanNETs. DAXX-knockdown (KD) and 
      knockout (KO) PanNET cells were analyzed for in vitro and vivo The target genes
      were screened by microarray and chromatin immunoprecipitation (ChIP) assays for
      DAXX, histone H3.3 and H3K9me3 complex. In clinicopathological features, low DAXX
      expression was significantly correlated with nonfunctional tumors, higher Ki-67
      index and WHO grade. Microarray and ChIP assays of DAXX-KD/KO identified 12 genes
      as the direct targets of DAXX transcriptional repressor. Among them, expression
      of five genes including STC2 was suppressed by DAXX/H3.3/H3K9me3 pathway. DAXX
      KD/KO cells enhanced sphere forming activity, but its effect was suppressed by
      knockdown of STC2 In xenograft models, tumorigenicity and tumor vessel density
      were significantly increased in DAXX-KO cells with high expression of STC2.
      Clinically, higher recurrence rate was recognized in PanNETs with low expression
      of DAXX and high expression of STC2 than others (P = 0.018). Our data suggest
      that DAXX plays as a tumor suppressor and DAXX/H3.3 complex suppresses target
      genes by promoting H3K9me3 in PanNETs. Combination of DAXX loss and its target
      gene STC2 overexpression might be effective biomarkers and therapeutic
      candidates.

PMID- 29599124
TI  - Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy.
AB  - ER-negative breast cancer includes most aggressive subtypes of breast cancer such
      as triple negative (TN) breast cancer. Excluded from hormonal and targeted
      therapies effectively used for other subtypes of breast cancer, standard
      chemotherapy is one of the primary treatment options for these patients. However,
      as ER- patients have shown highly heterogeneous responses to different
      chemotherapies, it has been difficult to select most beneficial chemotherapy
      treatments for them. In this study, we have simultaneously developed single drug
      biomarker models for four standard chemotherapy agents: paclitaxel (T), 5
      fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses
      and survival of ER- breast cancer patients treated with combination
      chemotherapies. We then flexibly combined these individual drug biomarkers for
      predicting patient outcomes of two independent cohorts of ER- breast cancer
      patients who were treated with different drug combinations of neoadjuvant
      chemotherapy. These individual and combined drug biomarker models significantly
      predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC =
      0.637, P = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P =
      0.056). The prediction was also significant for the TN subgroup of both cohorts
      (AUC = 0.60, 0.72, P = 0.043, 0.009). In survival analysis, our predicted
      responder patients showed significantly improved survival with a >17 months
      longer median PFS than the predicted non-responder patients for both ER- and TN
      subgroups (log-rank test P-value = 0.018 and 0.044). This flexible prediction
      capability based on single drug biomarkers may allow us to even select new drug
      combinations most beneficial to individual patients with ER- breast cancer.

PMID- 29599125
TI  - Establishment of human pluripotent stem cell-derived pancreatic beta-like cells
      in the mouse pancreas.
AB  - Type 1 diabetes is characterized by autoimmune destruction of beta cells located
      in pancreatic islets. However, tractable in vivo models of human pancreatic beta
      cells have been limited. Here, we generated xenogeneic human pancreatic beta-like
      cells in the mouse pancreas by orthotopic transplantation of stem cell-derived
      beta (SC-beta) cells into the pancreas of neonatal mice. The engrafted beta-like
      cells expressed beta cell transcription factors and markers associated with
      functional maturity. Engrafted human cells recruited mouse endothelial cells,
      suggesting functional integration. Human insulin was detected in the blood
      circulation of transplanted mice for months after transplantation and increased
      upon glucose stimulation. In addition to beta-like cells, human cells expressing
      markers for other endocrine pancreas cell types, acinar cells, and pancreatic
      ductal cells were identified in the pancreata of transplanted mice, indicating
      that this approach allows studying other human pancreatic cell types in the mouse
      pancreas. Our results demonstrate that orthotopic transplantation of human SC
      beta cells into neonatal mice is an experimental platform that allows the
      generation of mice with human pancreatic beta-like cells in the endogenous niche.

PMID- 29599127
TI  - Programmed cell death in yeast by thionin-like peptide from Capsicum annuum
      fruits involving activation of caspases and extracellular H+ flux.
AB  - CaThi is a thionin-like peptide isolated from fruits of Capsicum annuum, which
      has strong antimicrobial activity against bacteria, yeasts and filamentous fungi,
      and induced reactive oxygen species (ROS) in fungi. ROS are molecules that appear
      in the early stages of programmed cell death or apoptosis in fungi. Due to this
      fact, in this work we analyzed some events that may be related to process of
      apoptosis on yeast induced by CaThi. To investigate this possibility, we
      evaluated phosphatidylserine (PS) externalization, presence of active caspases
      and the ability of CaThi to bind to DNA in Candida tropicalis cells.
      Additionally, we investigated mitochondrial membrane potential, cell surface pH,
      and extracellular H+ fluxes in C. tropicalis cells after treatment with CaThi.
      Our results showed that CaThi induced PS externalization in the outer leaflet of
      the cell membrane, activation of caspases, and it had the ability for DNA binding
      and to dissipate mitochondrial membrane potential. In addition, the cell surface
      pH increased significantly when the C. tropicalis cells were exposed to CaThi
      which corroborates with ~96% inhibition on extracellular H+ efflux. Taking
      together, these data suggest that this peptide is capable of promoting an
      imbalance in pH homeostasis during yeast cell death playing a modulatory role in
      the H+ transport systems. In conclusion, our results strongly indicated that
      CaThi triggers apoptosis in C. tropicalis cells, involving a pH signaling
      mechanism.

PMID- 29599126
TI  - Interferon regulatory factor 1 inactivation in human cancer.
AB  - Interferon regulatory factors (IRFs) are a group of closely related proteins
      collectively referred to as the IRF family. Members of this family were
      originally recognized for their roles in inflammatory responses; however, recent
      research has suggested that they are also involved in tumor biology. This review
      focusses on current knowledge of the roles of IRF-1 and IRF-2 in human cancer,
      with particular attention paid to the impact of IRF-1 inactivation. The different
      mechanisms underlying IRF-1 inactivation and their implications for human cancers
      and the potential importance of IRF-1 in immunotherapy are also summarized.

PMID- 29599128
TI  - Internal biliary drainage superior to external biliary drainage in improving gut
      mucosa barrier because of goblet cells and mucin-2 up-regulation.
AB  - : Backgroud: Obstructive jaundice increases intestinal permeability, but the
      pathological mechanisms remain obscure, which results in debates about the
      necessity of performing preoperative biliary drainage in patients with
      obstructive jaundice. Mucin-2 (MUC2) and goblet cells regulated by bile acids
      play an important role in maintaining the function of intestinal mucosal barrier.
      The present study was to investigate the role of goblet cells and MUC2 in
      obstructive jaundice and evaluate the effect of biliary drainage on intestinal
      permeability. STUDY DESIGN: We enrolled patients with malignant biliary
      obstruction and controls. We also did animal studies with four groups of rats:
      sham operation, obstructive jaundice, internal biliary drainage, and external
      biliary drainage. Histopathological analysis, biochemical measurement, and
      electron microscopy examination were done on pertinent samples. RESULTS: Compared
      with the control group, the small intestinal mucosa was significantly damaged;
      goblet cells and MUC2 were significantly decreased and serum endotoxin level was
      significantly increased in patients and rats with obstructive jaundice. Biliary
      drainage, especially internal biliary drainage, significantly increased goblet
      cells and MUC2 and attenuated the damage of small intestinal mucosa. CONCLUSIONS:
      In obstructive jaundice condition, goblet cells and MUC2 were reduced which were
      involved in the damage of intestinal mucosa barrier; biliary drainage increased
      goblet cells and MUC2, repaired mucosa layer and restored the intestinal mucosa
      barrier function.

PMID- 29599130
TI  - Bring me a sunshine act: five minutes with . . . Peter Gordon.

PMID- 29599131
TI  - Hunger strike renews concerns over health in UK detention centres.

PMID- 29599129
TI  - 5-aminoisoquinoline improves renal function and fibrosis during recovery phase of
      cisplatin-induced acute kidney injury in rats.
AB  - The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5
      AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction
      and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney
      injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each
      group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a
      subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5
      AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before
      and 24 h after CisPt treatment. Thirteen days after the treatment, rats were
      housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt
      treated rats showed increased diuresis, N-acetyl-beta-d-glucosaminidase (NAG)
      excretion, glucosuria and sodium fractional excretion (NaFE), and decreased
      creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG
      excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and
      creatinine concentrations, while 5-AIQ treatment decreased these variables to the
      levels of control group. 5-AIQ completely prevented the body weight loss evoked
      by CisPt treatment. CisPt also induced an increased renal expression of PAR
      polymer, alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1
      (TGF-beta1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ
      group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment.
      We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term
      nephrotoxic effects associated with the CisPt treatment, preventing renal
      dysfunction and body weight decrease and ameliorating tubular lesions and
      collagen deposition.

PMID- 29599132
TI  - CaMKII (Ca2+/Calmodulin-Dependent Kinase II) in Mitochondria of Smooth Muscle
      Cells Controls Mitochondrial Mobility, Migration, and Neointima Formation.
AB  - OBJECTIVE: The main objective of this study is to define the mechanisms by which
      mitochondria control vascular smooth muscle cell (VSMC) migration and impact
      neointimal hyperplasia. APPROACH AND RESULTS: The multifunctional CaMKII
      (Ca2+/calmodulin-dependent kinase II) in the mitochondrial matrix of VSMC drove a
      feed-forward circuit with the mitochondrial Ca2+ uniporter (MCU) to promote
      matrix Ca2+ influx. MCU was necessary for the activation of mitochondrial CaMKII
      (mtCaMKII), whereas mtCaMKII phosphorylated MCU at the regulatory site S92 that
      promotes Ca2+ entry. mtCaMKII was necessary and sufficient for platelet-derived
      growth factor-induced mitochondrial Ca2+ uptake. This effect was dependent on
      MCU. mtCaMKII and MCU inhibition abrogated VSMC migration and mitochondrial
      translocation to the leading edge. Overexpression of wild-type MCU, but not MCU
      S92A, mutant in MCU-/- VSMC rescued migration and mitochondrial mobility.
      Inhibition of microtubule, but not of actin assembly, blocked mitochondrial
      mobility. The outer mitochondrial membrane GTPase Miro-1 promotes mitochondrial
      mobility via microtubule transport but arrests it in subcellular domains of high
      Ca2+ concentrations. In Miro-1-/- VSMC, mitochondrial mobility and VSMC migration
      were abolished, and overexpression of mtCaMKII or a CaMKII inhibitory peptide in
      mitochondria (mtCaMKIIN) had no effect. Consistently, inhibition of mtCaMKII
      increased and prolonged cytosolic Ca2+ transients. mtCaMKII inhibition diminished
      phosphorylation of focal adhesion kinase and myosin light chain, leading to
      reduced focal adhesion turnover and cytoskeletal remodeling. In a transgenic
      model of selective mitochondrial CaMKII inhibition in VSMC, neointimal
      hyperplasia was significantly reduced after vascular injury. CONCLUSIONS: These
      findings identify mitochondrial CaMKII as a key regulator of mitochondrial Ca2+
      uptake via MCU, thereby controlling mitochondrial translocation and VSMC
      migration after vascular injury.

PMID- 29599133
TI  - LAL (Lysosomal Acid Lipase) Promotes Reverse Cholesterol Transport In Vitro and
      In Vivo.
AB  - OBJECTIVE: To explore the role of LAL (lysosomal acid lipase) in macrophage
      cholesterol efflux and whole-body reverse cholesterol transport. APPROACH AND
      RESULTS: Immortalized peritoneal macrophages from lal-/- mice showed reduced
      expression of ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding
      cassette transporter G1), reduced production of the regulatory oxysterol 27
      hydroxycholesterol, and impaired suppression of cholesterol synthesis on exposure
      to acetylated low-density lipoprotein when compared with lal+/+ macrophages. LAL
      deficient mice also showed reduced hepatic ABCG5 (ATP-binding cassette
      transporter G5) and ABCG8 (ATP-binding cassette transporter G8) expression
      compared with lal+/+ mice. LAL-deficient macrophages loaded with [3H]-cholesteryl
      oleate-labeled acetylated low-density lipoprotein showed impaired efflux of
      released [3H]-cholesterol to apoA-I (apolipoprotein A-I), with normalization of
      [3H]-cholesteryl ester levels and partial correction of ABCA1 expression and
      cholesterol efflux to apoA-I when treated with exogenous rhLAL (recombinant human
      LAL protein). LAL-deficient mice injected intraperitoneally with lal-/-
      macrophages cholesterol loaded and labeled in the same way exhibited only 1.55+/
      0.35% total injected [3H]-cholesterol counts appearing in the feces for 48 h
      (n=30), compared with 5.38+/-0.92% in lal+/+ mice injected with labeled lal+/+
      macrophages (n=27), P<0.001. To mimic the therapeutic condition of delivery of
      supplemental LAL in vivo, injection of labeled lal-/- macrophages into lal+/+
      mice resulted in a significant increase in reverse cholesterol transport (2.60+/
      0.46% of 3H-cholesterol counts in feces at 48 hours [n=19]; P<0.001 when compared
      with injection into lal-/- mice). CONCLUSIONS: These results indicate a critical
      role for LAL in promoting both macrophage and whole-body reverse cholesterol
      transport and the ability of supplemental LAL to be taken up and correct reverse
      cholesterol transport in vivo.

PMID- 29599134
TI  - Extracellular and Intracellular Cyclophilin A, Native and Post-Translationally
      Modified, Show Diverse and Specific Pathological Roles in Diseases.
AB  - CypA (cyclophilin A) is a ubiquitous and highly conserved protein with peptidyl
      prolyl isomerase activity. Because of its highly abundant level in the cytoplasm,
      most studies have focused on the roles of CypA as an intracellular protein.
      However, emerging evidence suggests an important role for extracellular CypA in
      the pathogenesis of several diseases through receptor (CD147 or other)-mediated
      autocrine and paracrine signaling pathways. In this review, we will discuss the
      shared and unique pathological roles of extracellular and intracellular CypA in
      human cardiovascular diseases. In addition, the evolving role of post
      translational modifications of CypA in the pathogenesis of disease is discussed.
      Finally, recent studies with drugs specific for extracellular CypA show its
      importance in disease pathogenesis in several animal models and make
      extracellular CypA a new therapeutic target.

PMID- 29599135
TI  - PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in
      Mice.
AB  - OBJECTIVE: PAR2 (protease-activated receptor 2)-dependent signaling results in
      augmented inflammation and has been implicated in the pathogenesis of several
      autoimmune conditions. The objective of this study was to determine the effect of
      PAR2 deficiency on the development of atherosclerosis. APPROACH AND RESULTS: PAR2
      mRNA and protein expression is increased in human carotid artery and mouse aortic
      arch atheroma versus control carotid and aortic arch arteries, respectively. To
      determine the effect of PAR2 deficiency on atherosclerosis, male and female low
      density lipoprotein receptor-deficient (Ldlr-/-) mice (8-12 weeks old) that were
      Par2+/+ or Par2-/- were fed a fat- and cholesterol-enriched diet for 12 or 24
      weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic
      root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma
      cholesterol concentrations or lipoprotein distributions. Bone marrow
      transplantation showed that PAR2 on nonhematopoietic cells contributed to
      atherosclerosis. PAR2 deficiency significantly attenuated levels of the
      chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in
      atherosclerotic lesions. Mechanistic studies using isolated primary vascular
      smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2
      and Cxcl1 mRNA expression and protein release into the supernatant resulting in
      less monocyte migration. CONCLUSIONS: Our results indicate that PAR2 deficiency
      is associated with attenuation of atherosclerosis and may reduce lesion
      progression by blunting Ccl2- and Cxcl1-induced monocyte infiltration.

PMID- 29599136
TI  - Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation
      in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)
      Null Mice-Brief Report.
AB  - OBJECTIVE: Inflammatory macrophages promote the development of atherosclerosis.
      We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator
      of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells
      promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on
      atherosclerosis has not been shown. APPROACH AND RESULTS: To determine the role
      of myeloid Dab2 in atherosclerosis, Ldlr-/- mice were reconstituted with either
      Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent
      with our previous finding that Dab2 inhibits NFkappaB (nuclear factor kappa-light
      chain-enhancer of activated B cells) signaling in macrophages, Ldlr-/- mice
      reconstituted with Dab2-deficient bone marrow had increased systemic inflammation
      as evidenced by increased serum IL-6 (interleukin-6) levels and increased
      inflammatory cytokine expression levels in liver. Serum lipid levels were
      significantly lower in Ldlr-/- mice reconstituted with Dab2-deficient bone
      marrow, and further examination of livers from these mice revealed drastically
      increased inflammatory tissue damage and massive infiltration of immune cells.
      Surprisingly, the atherosclerotic lesion burden in Ldlr-/- mice reconstituted
      with Dab2-deficient bone marrow was decreased compared with Ldlr-/- mice
      reconstituted with wild-type bone marrow. Further analysis of aortic root
      sections revealed increased macrophage content and evidence of increased
      apoptosis in lesions from Ldlr-/- mice reconstituted with Dab2-deficient bone
      marrow but no difference in collagen or alpha-smooth muscle actin content.
      CONCLUSIONS: Dab2 deficiency in myeloid cells promotes inflammation in livers and
      atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless,
      decreased serum lipids as a result of massive inflammatory liver damage may
      preclude an appreciable increase in atherosclerotic lesion burden in mice
      reconstituted with Dab2-deficient bone marrow.

PMID- 29599137
TI  - Afadin Facilitates Vascular Endothelial Growth Factor-Induced Network Formation
      and Migration of Vascular Endothelial Cells by Inactivating Rho-Associated Kinase
      Through ArhGAP29.
AB  - OBJECTIVE: We previously reported that afadin, an actin filament-binding protein,
      regulated vascular endothelial growth factor-induced angiogenesis. However, the
      underlying molecular mechanisms are poorly understood. Here, we investigated the
      mechanisms of how Rho-associated kinase is activated in afadin-knockdown human
      umbilical vein endothelial cells (HUVECs) and how its activation is involved in
      defects of vascular endothelial growth factor-induced network formation and
      migration of the cells. APPROACH AND RESULTS: Knockdown of afadin or ArhGAP29, a
      GTPase-activating protein for RhoA, increased Rho-associated kinase activity and
      reduced the vascular endothelial growth factor-induced network formation and
      migration of cultured HUVECs, accompanied by the defective formation of membrane
      protrusions, such as lamellipodia and peripheral ruffles. Treatment of the afadin
      or ArhGAP29-knockdown HUVECs with Rho-associated kinase inhibitors, Y-27632 or
      fasudil, partially restored the reduced network formation and migration as well
      as the defective formation of membrane protrusions. ArhGAP29 bound to afadin and
      was colocalized with afadin at the leading edge of migrating HUVECs. The
      defective formation of membrane protrusions in ArhGAP29-knockdown HUVECs was
      restored by expression of mutant ArhGAP29 that bound to afadin and contained a
      RhoGAP domain but not mutant ArhGAP29 that could bind to afadin and lacked the
      RhoGAP domain or mutant ArhGAP29 that could not bind to afadin and contained the
      RhoGAP domain. This suggested the requirement of both the interaction of afadin
      with ArhGAP29 and RhoGAP activity of ArhGAP29 for migration of HUVECs.
      CONCLUSIONS: Our results highlight a critical role of the afadin-ArhGAP29 axis
      for the regulation of Rho-associated kinase activity during vascular endothelial
      growth factor-induced network formation and migration of HUVECs.

PMID- 29599138
TI  - Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis
      Suppressive Potential of Regulatory T-Cells.
AB  - OBJECTIVE: Atherosclerosis is an age-related disease characterized by systemic
      oxidative stress and low-grade inflammation. The role of telomerase and telomere
      length in atherogenesis remains contentious. Short telomeres of peripheral
      leukocytes are predictive for coronary artery disease. Conversely, attenuated
      telomerase has been demonstrated to be protective for atherosclerosis. Hence, a
      potential causative role of telomerase in atherogenesis is critically debated.
      APPROACH AND RESULTS: In this study, we used multiple mouse models to investigate
      the regulation of telomerase under oxidative stress as well as its impact on
      atherogenesis in vitro and in vivo. Using primary lymphocytes and myeloid cell
      cultures, we demonstrate that cultivation under hyperoxic conditions induced
      oxidative stress resulting in chronic activation of CD4+ cells and significantly
      reduced CD4+ T-cell proliferation. The latter was telomerase dependent because
      oxidative stress had no effect on the proliferation of primary lymphocytes
      isolated from telomerase knockout mice. In contrast, myeloid cell proliferation
      was unaffected by oxidative stress nor reliant on telomerase. Telomerase reverse
      transcriptase deficiency had no effect on regulatory T-cell (Treg) numbers in
      vivo or suppressive function ex vivo. Adoptive transfer of telomerase reverse
      transcriptase-/- Tregs into Rag2-/- ApoE-/- (recombination activating gene
      2/apolipoprotein E) double knockout mice demonstrated that telomerase function
      was not required for the ability of Tregs to protect against atherosclerosis.
      However, telomere length was critical for Treg function. CONCLUSIONS: Telomerase
      contributes to lymphocyte proliferation but plays no major role in Treg function,
      provided that telomere length is not critically short. We suggest that oxidative
      stress may contribute to atherosclerosis via suppression of telomerase and
      acceleration of telomere attrition in Tregs.

PMID- 29599139
TI  - Protective Role of mPGES-1 (Microsomal Prostaglandin E Synthase-1)-Derived PGE2
      (Prostaglandin E2) and the Endothelial EP4 (Prostaglandin E Receptor) in Vascular
      Responses to Injury.
AB  - OBJECTIVE: Deletion of mPGES-1 (microsomal prostaglandin E synthase-1)-an anti
      inflammatory target alternative to COX (cyclooxygenase)-2-attenuates injury
      induced neointima formation in mice. This is attributable to the augmented levels
      of PGI2 (prostacyclin)-a known restraint of the vascular response to injury,
      acting via IP (I prostanoid receptor). To examine the role of mPGES-1-derived
      PGE2 (prostaglandin E2) in vascular remodeling without the IP. APPROACH AND
      RESULTS: Mice deficient in both IP and mPGES-1 (DKO [double knockout] and
      littermate controls [IP KO (knockout)]) were subjected to angioplasty wire
      injury. Compared with the deletion of IP alone, coincident deletion of IP and
      mPGES-1 increased neointima formation, without affecting media area. Early
      pathological changes include impaired reendothelialization and increased
      leukocyte invasion in neointima. Endothelial cells (ECs), but not vascular smooth
      muscle cells, isolated from DKOs exhibited impaired cell proliferation.
      Activation of EP (E prostanoid receptor) 4 (and EP2, to a lesser extent), but not
      of EP1 or EP3, promoted EC proliferation. EP4 antagonism inhibited proliferation
      of mPGES-1-competent ECs, but not of mPGES-1-deficient ECs, which showed
      suppressed PGE2 production. EP4 activation inhibited leukocyte adhesion to ECs in
      vitro, promoted reendothelialization, and limited neointima formation post-injury
      in the mouse. Endothelium-restricted deletion of EP4 in mice suppressed
      reendothelialization, increased neointimal leukocytes, and exacerbated neointimal
      formation. CONCLUSIONS: Removal of the IP receptors unmasks a protective role of
      mPGES-1-derived PGE2 in limiting injury-induced vascular hyperplasia. EP4, in the
      endothelial compartment, is essential to promote reendothelialization and
      restrain neointimal formation after injury. Activating EP4 bears therapeutic
      potential to prevent restenosis after percutaneous coronary intervention.

PMID- 29599140
TI  - Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation
      Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.
AB  - OBJECTIVE: B cells promote or protect development of atherosclerosis. In this
      study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster
      of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein)
      expression by follicular B (FO B) cells in development of atherosclerosis
      together with the effects of IgG purified from atherosclerotic mice. APPROACH AND
      RESULTS: Using mixed chimeric Ldlr-/- mice whose B cells are deficient in MHCII
      or CD40, we demonstrate that these molecules are critical for the proatherogenic
      actions of FO B cells. During development of atherosclerosis, these deficiencies
      affected T-B cell interactions, germinal center B cells, plasma cells, and IgG.
      As FO B cells differentiating into plasma cells require Blimp-1, we also assessed
      its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly
      attenuated atherosclerosis and immunoglobulin-including IgG production,
      preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also
      attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic
      core. To determine the importance of IgG for atherosclerosis, we purified IgG
      from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic
      mice into Ldlr-/- mice whose B cells are Blimp-1-deficient increased
      atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic
      lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and
      necrotic core size. CONCLUSIONS: The mechanism by which FO B cells promote
      atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp
      1. FO B cell differentiation into IgG-producing plasma cells also is critical for
      their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG
      may provide novel therapeutic strategies to prevent atherosclerosis and its
      adverse cardiovascular complications.

PMID- 29599141
TI  - Switch in Laminin beta2 to Laminin beta1 Isoforms During Aging Controls
      Endothelial Cell Functions-Brief Report.
AB  - OBJECTIVE: Endothelial cells play important roles in tissue homeostasis and
      vascularization, a function that is impaired by aging. Here, we aim to decipher
      the role of the microenvironment underlying the impairment of endothelial cell
      functions by aging. APPROACH AND RESULTS: RNA sequencing of isolated cardiac
      endothelial cells derived from young and 18-month-old mouse hearts revealed that
      aging affects the endothelial expression of genes encoding extracellular matrix
      proteins, specifically the laminin beta1 (Lamb1) and laminin beta2 (Lamb2)
      chains. Whereas Lamb1 was upregulated, Lamb2 was decreased in endothelial cells
      in old mice compared with young controls. A similar change in expression patterns
      was observed after induction of acute myocardial infarction. Mimicking aging and
      injury conditions by plating endothelial cells on laminin beta1-containing
      laminin 411 matrix impaired endothelial cell adhesion, migration, and tube
      formation and augmented endothelial-to-mesenchymal transition and endothelial
      detachment compared with laminin 421, which contains the laminin beta2 chain.
      Because laminins can signal via integrin receptors, we determined the activation
      of ITGB1 (integrin beta1). Laminin 421 coating induced a higher activation of
      ITGB1 compared with laminin 411. siRNA-mediated silencing of ITGB1 reduced
      laminin beta2-dependent adhesion, suggesting that laminin beta2 more efficiently
      activates ITGB1. CONCLUSIONS: Mimicking age-related modulation of laminin beta1
      versus beta2 chain expression changes the functional properties and phenotype of
      endothelial cells. The dysregulation of the extracellular matrix during vascular
      aging may contribute to age-associated impairment of organ function and fibrosis.

PMID- 29599142
TI  - Pevonedistat, a new partner for 5-azacitidine.

PMID- 29599143
TI  - Fire behind the fury: IL-18 and MAS.

PMID- 29599144
TI  - ARF way to Ph+ ALL stratification?

PMID- 29599145
TI  - Treating chronic GVHD-induced fibrosis?

PMID- 29599146
TI  - A clandestine worm.

PMID- 29599147
TI  - Systemic mastocytosis with concurrent multiple myeloma.

PMID- 29599148
TI  - Magarotto V, Bringhen S, Offidani M, et al. Triplet vs doublet lenalidomide
      containing regimens for the treatment of elderly patients with newly diagnosed
      multiple myeloma. Blood. 2016;127(9):1102-1108.

PMID- 29599150
TI  - Genome Sequence of Coxiella-Like Endosymbiont Strain CLE-RmD, a Bacterial Agent
      in the Cattle Tick (Rhipicephalus microplus) Deutsch Strain.
AB  - We report a partial genome sequence for the Coxiella-like endosymbiont strain CLE
      RmD, assembled from metagenomics data obtained from the southern cattle tick
      (Rhipicephalus microplus) Deutsch strain.

PMID- 29599151
TI  - Draft Genome Sequences of Two Epidemic OXA-48-Producing Klebsiella pneumoniae
      Clinical Strains Isolated during a Large Outbreak in Spain.
AB  - We report here the draft genome sequences of Klebsiella pneumoniae strains Kp1803
      and Kp3380 isolated during a large outbreak at A Coruna Hospital in Spain. The
      final genome assemblies for Kp1803 and Kp3380 comprise approximately 6.6 and 6.1
      Mb, respectively, and both strains have G+C contents of 57.2%.

PMID- 29599149
TI  - Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium
      dysregulation.
AB  - Aggregation of alpha-synuclein is a hallmark of Parkinson's disease and dementia
      with Lewy bodies. We here investigate the relationship between cytosolic Ca2+ and
      alpha-synuclein aggregation. Analyses of cell lines and primary culture models of
      alpha-synuclein cytopathology reveal an early phase with reduced cytosolic Ca2+
      levels followed by a later Ca2+ increase. Aggregated but not monomeric alpha
      synuclein binds to and activates SERCA in vitro, and proximity ligation assays
      confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA)
      normalises both the initial reduction and the later increase in cytosolic Ca2+
      CPA protects the cells against alpha-synuclein-aggregate stress and improves
      viability in cell models and in Caenorhabditis elegans in vivo Proximity ligation
      assays also reveal an increased interaction between alpha-synuclein aggregates
      and SERCA in human brains affected by dementia with Lewy bodies. We conclude that
      alpha-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA
      activity is neuroprotective, indicating that SERCA and down-stream processes may
      be therapeutic targets for treating alpha-synucleinopathies.

PMID- 29599152
TI  - Draft Genome Sequence of a Mycobacterium heckeshornense Clinical Isolate.
AB  - We report here the draft genome sequence of Mycobacterium heckeshornense,
      isolated from the sputum of a patient admitted to a tuberculosis hospital with
      suspected pulmonary tuberculosis.

PMID- 29599153
TI  - Complete Genome Sequencing of Eight Brucella abortus Biovar 1 Strains Isolated
      from Water Buffalo.
AB  - Brucellosis is a zoonotic disease caused by bacteria of the genus Brucella The
      disease is endemic in many areas, causing chronic infections responsible for
      reproductive disorders in infected animals. Here, we present eight complete
      genome assemblies of eight Brucella abortus strains isolated from water buffaloes
      farmed in the Campania region.

PMID- 29599154
TI  - Draft Genome Sequences of Two Novel Salmonella enterica subsp. enterica Strains
      Isolated from Low-Moisture Foods with Applications in Food Safety Research.
AB  - The genomes of two strains of Salmonella enterica subsp. enterica serovar Cubana
      and serovar Muenchen, isolated from dry hazelnuts and chia seeds, respectively,
      were sequenced using the Illumina MiSeq platform, assembled de novo using the
      overlap-layout-consensus method, and aligned to their respective most identical
      sequence genome scaffolds using MUMMER and BLAST searches.

PMID- 29599155
TI  - Complete Genome Sequences of Six Measles Virus Strains.
AB  - Genetic characterization of wild-type measles virus (MV) strains is a critical
      component of measles surveillance and molecular epidemiology. We have obtained
      complete genome sequences of six MV strains belonging to different genotypes,
      using random-primed next generation sequencing.

PMID- 29599156
TI  - Draft Genome Sequence of Bacillus paralicheniformis F47, Isolated from an
      Algerian Salty Lake.
AB  - Bacillus paralicheniformis F47 was isolated from a salty lake in Ain Baida
      Ouargla, southern Algeria. The genome contains genes for the production of
      several bioactive secondary metabolites, including the siderophore bacillibactin,
      the lipopeptides fengycin, surfactin, and lichenysin, the antibiotics bacitracin
      and kanosamine, and a putative circular bacteriocin.

PMID- 29599157
TI  - Draft Genome Sequence of an NDM-1- and KPC-2-Coproducing Hypervirulent Carbapenem
      Resistant Klebsiella pneumoniae Strain Isolated from Burn Wound Infections.
AB  - We report here the draft genome sequence of an NDM-1- and KPC-2-coproducing
      hypervirulent carbapenem-resistant Klebsiella pneumoniae strain, isolated from a
      58-year-old male in the People's Republic of China with a burn injury.

PMID- 29599158
TI  - Draft Genome Sequence of Pseudomonas gingeri Strain LMG 5327, the Causative Agent
      of Ginger Blotch in Agaricus bisporus.
AB  - The draft genome sequence of Pseudomonas gingeri LMG 5327 (NCPPB 3146), the
      causative agent of ginger blotch in Agaricus bisporus, is reported. Together with
      another mushroom pathogen, Pseudomonas agarici, it belongs to a distinct
      phylogenomic group.

PMID- 29599159
TI  - Draft Genome Sequence of the First New Delhi Metallo-beta-Lactamase (NDM-1)
      Producing Escherichia coli Strain Isolated in Peru.
AB  - We present here the draft genome sequence of the first New Delhi metallo-beta
      lactamase (NDM-1)-producing Escherichia coli strain, belonging to sequence type
      155 (ST155), isolated in Peru. Assembly of this draft genome resulted in
      5,061,184 bp, revealing a clinically significant resistome for beta-lactams,
      aminoglycosides, tetracyclines, phenicols, sulfonamides, trimethoprim, and
      fluoroquinolones.

PMID- 29599160
TI  - Whole-Genome Sequence of Acetobacter orientalis Strain FAN1, Isolated from
      Caucasian Yogurt.
AB  - In traditional Caucasian yogurt, Acetobacter orientalis bacteria play important
      roles in the fermentation of milk in concert with Lactococcus bacteria. In this
      study, an A. orientalis strain, FAN1, was newly isolated from commercially
      available Caucasian yogurt, and its whole-genome sequence was determined,
      identifying two circular DNAs.

PMID- 29599161
TI  - Genome Sequence of the Amphotericin B-Resistant Candida duobushaemulonii Strain
      B09383.
AB  - Candida duobushaemulonii is a drug-resistant yeast that can cause invasive
      candidiasis. Here, we report the first genome sequence of C. duobushaemulonii,
      isolate B09383, generated using PacBio sequencing technology. The estimated
      genome size was 12.5 Mb with a GC content of 46.84%.

PMID- 29599162
TI  - Draft Genome Sequence of Escherichia coli KL53.
AB  - Here, we report the draft genome sequence of a clinical isolate of the
      uropathogenic strain Escherichia coli KL53. A total of 5,083,632 bp was de novo
      assembled into 170 contigs containing 89 RNAs and 5,034 protein-coding genes.
      Remarkable is the presence of the tellurite resistance (ter) operon on a plasmid.

PMID- 29599163
TI  - Correction for Tiba-Casas et al., "Draft Genome Sequence of a Pathogenic Vibrio
      vulnificus Strain Isolated in Brazil".

PMID- 29599165
TI  - Improving the quality of care delivered to adolescents in Europe: a time to
      invest.

PMID- 29599164
TI  - Incident CTS in a large pooled cohort study: associations obtained by a Job
      Exposure Matrix versus associations obtained from observed exposures.
AB  - BACKGROUND: There is growing use of a job exposure matrix (JEM) to provide
      exposure estimates in studies of work-related musculoskeletal disorders; few
      studies have examined the validity of such estimates, nor did compare
      associations obtained with a JEM with those obtained using other exposures.
      OBJECTIVE: This study estimated upper extremity exposures using a JEM derived
      from a publicly available data set (Occupational Network, O*NET), and compared
      exposure-disease associations for incident carpal tunnel syndrome (CTS) with
      those obtained using observed physical exposure measures in a large prospective
      study. METHODS: 2393 workers from several industries were followed for up to 2.8
      years (5.5 person-years). Standard Occupational Classification (SOC) codes were
      assigned to the job at enrolment. SOC codes linked to physical exposures for
      forceful hand exertion and repetitive activities were extracted from O*NET. We
      used multivariable Cox proportional hazards regression models to describe
      exposure-disease associations for incident CTS for individually observed physical
      exposures and JEM exposures from O*NET. RESULTS: Both exposure methods found
      associations between incident CTS and exposures of force and repetition, with
      evidence of dose-response. Observed associations were similar across the two
      methods, with somewhat wider CIs for HRs calculated using the JEM method.
      CONCLUSION: Exposures estimated using a JEM provided similar exposure-disease
      associations for CTS when compared with associations obtained using the 'gold
      standard' method of individual observation. While JEMs have a number of
      limitations, in some studies they can provide useful exposure estimates in the
      absence of individual-level observed exposures.

PMID- 29599166
TI  - Tramadol, breast feeding and safety in the newborn.

PMID- 29599168
TI  - Correction: The Little Prince: is not a glimpse into the world of autism.

PMID- 29599167
TI  - Quality of life in young people with congenital heart disease is better than
      expected.
AB  - OBJECTIVES: Improved treatments for patients with congenital heart disease (CHD)
      have led to a growing interest in long-term functional outcomes such as health
      related quality of life (HRQoL). Studies on HRQoL in children with CHD have
      contradicting results. Therefore, we compared HRQoL of children with CHD with
      that of current healthy peers and stratify CHD cases by severity and diagnostic
      subgroups. METHODS: We included 514 patients (191 girls) aged 7-17 (12.9+/-3.1)
      years who were recruited at our institution between July 2014 and May 2017. The
      self-reported and age-adapted KINDL questionnaire was used to assess HRQoL.
      Patient data were compared with that of a recent control group of 734 healthy
      children (346 girls, 13.4+/-2.1 years). RESULTS: Patients with CHD scored at
      least as high as healthy peers in HRQoL (CHD: 78.6+/-9.8; healthy: 75.6+/-10.1;
      P<0.001). After correction for sex and age, patients with CHD presented a 2.3
      point higher HRQoL (P<0.001). The sex-specific and age-specific analyses showed
      that there were no differences between boys with and without CHD in childhood
      (P=0.255), but in adolescence, boys with CHD had on average 3.9-point higher
      scores (P=0.001), whereas girls with CHD had statistically higher HRQoL
      perception than healthy girls in childhood (4.2 points; P=0.003) and adolescence
      (4.2 points; P=0.005). There were no differences between the severity classes or
      diagnostic subgroups in the total HRQoL score or in the six subdomains.
      CONCLUSION: The high HRQoL in young patients with CHD suggests that they can cope
      well with their disease burden. This holds true for all severity classes and
      diagnostic subgroups.

PMID- 29599169
TI  - Aneurysmal Parent Artery-Specific Inflow Conditions for Complete and Incomplete
      Circle of Willis Configurations.
AB  - BACKGROUND AND PURPOSE: Hemodynamics are thought to play a role in intracranial
      aneurysm growth and rupture. Computational fluid dynamics is frequently performed
      to assess intra-aneurysmal hemodynamics, using generalized flow waveforms of
      healthy volunteers as inflow boundary conditions. The purpose of this study was
      to assess differences in inflow conditions for different aneurysmal parent artery
      locations and variations of circle of Willis configurations. MATERIALS AND
      METHODS: In a series of 96 patients with 103 aneurysms, velocity measurements
      were acquired using 2D phase-contrast MR imaging perpendicular to the aneurysmal
      parent arteries in the circle of Willis. Circle of Willis configurations were
      inspected for variations using multiple overlapping thin-slab-acquisition MRAs.
      Flow rates, velocity magnitudes, and pulsatility indices were calculated for each
      parent artery location in subgroups of complete and incomplete circle of Willis
      configurations. RESULTS: Flow rates, velocity magnitudes, and pulsatility indices
      were significantly different among aneurysmal parent arteries. Incomplete circle
      of Willis configurations were observed in 24% of the cases. Significantly lower
      basilar artery flow rates were observed in configurations with hypoplastic P1
      segments. Significantly higher A1 flow rates were observed in configurations with
      a hypoplastic contralateral A1 segment. CONCLUSIONS: Inflow conditions vary
      substantially between aneurysmal parent arteries and circle of Willis
      configurations. We have created a collection of parent artery-specific inflow
      conditions tailored to the patient-specific circle of Willis configuration that
      can be used in future computational fluid dynamics studies analyzing intra
      aneurysmal hemodynamics.

PMID- 29599170
TI  - Blood Flow Mimicking Aneurysmal Wall Enhancement: A Diagnostic Pitfall of Vessel
      Wall MRI Using the Postcontrast 3D Turbo Spin-Echo MR Imaging Sequence.
AB  - Our aim was to compare the detectability of aneurysmal wall enhancement in
      unruptured intracranial aneurysms between conventional and motion-sensitized
      driven equilibrium-prepared postcontrast 3D T1-weighted TSE sequences (sampling
      perfection with applicationoptimized contrasts by using different flip angle
      evolution, SPACE). Twenty-two patients with 30 unruptured intracranial aneurysms
      were scanned at 3T. Aneurysmal wall enhancement was more significantly detected
      using conventional compared with motion-sensitized driven equilibrium-prepared
      SPACE sequences (10/30 versus 2/30, P < .0001). Contrast-to-noise ratio
      measurements did not differ between conventional and motion-sensitized driven
      equilibrium-prepared sequences (P = .51). Flowing blood can mimic aneurysmal wall
      enhancement using conventional SPACE sequences with potential implications for
      patient care.

PMID- 29599171
TI  - Signal Change of Acute Cortical and Juxtacortical Microinfarction on Follow-Up
      MRI.
AB  - BACKGROUND AND PURPOSE: Although the clinical importance of cortical
      microinfarcts has become well-recognized recently, the evolution of cortical
      microinfarcts on MR imaging is not fully understood. The aim of this study was to
      examine the temporal changes in acute cortical microinfarcts using susceptibility
      weighted imaging and conventional MR imaging. MATERIALS AND METHODS: Patients
      with acute infarcts located in the cortical and/or juxtacortical region measuring
      <=10 mm in axial diameter based on diffusion-weighted imaging who had a follow-up
      3T MR imaging were retrospectively included in the study. All lesions did not
      show hypointensity on initial T2*WI. For cortical and/or juxtacortical
      microinfarcts detected on initial DWI, 2 neuroradiologists evaluated the follow
      up MR imaging (T2WI, FLAIR, T2*WI, and SWI) and assessed lesion signal
      intensities and locations (cortical microinfarcts or microinfarcts with
      juxtacortical white matter involvement). RESULTS: On initial DWI, 2 radiologists
      observed 180 cortical and/or juxtacortical microinfarcts in 35 MR imaging
      examinations in 25 patients; on follow-up, the neuroradiologists identified 29
      cortical microinfarcts (16%) on T2WI, 9 (5%) on FLAIR, 4 (2%) on T2*, and 97
      (54%) on SWI. All cortical microinfarcts detected with any follow-up MR imaging
      showed hyperintensity on T2WI/FLAIR and/or hypointensity on T2*WI and SWI.
      CONCLUSIONS: SWI revealed conversion (paramagnetic susceptibility changes) of
      acute cortical microinfarcts, suggesting that a substantial number of cortical
      microinfarcts may contain hemorrhagic components.

PMID- 29599172
TI  - Submandibular Gland Transfer: A Potential Imaging Pitfall.
AB  - BACKGROUND AND PURPOSE: The Seikaly and Jha submandibular gland transfer surgery
      is performed to facilitate gland shielding during radiation therapy for head and
      neck tumors to circumvent radiation-induced xerostomia. It results in an
      asymmetric postsurgical appearance of the submandibular and submental spaces. Our
      purpose was to characterize the morphologic and enhancement characteristics of
      the transferred submandibular gland and identify potential pitfalls in
      postoperative radiologic interpretation. MATERIALS AND METHODS: This
      retrospective study identified patients with head and neck cancer who had
      undergone the submandibular gland transfer procedure at our institution. Chart
      reviews were performed to identify relevant oncologic histories and therapies. CT
      and MR neck imaging was reviewed to characterize morphologic and enhancement
      characteristics of the pre- and postoperative submandibular glands, as well as
      interpretive accuracy. RESULTS: Eleven patients with oropharyngeal and
      nasopharyngeal squamous cell carcinomas who underwent submandibular gland
      transfer were identified. The transferred glands were significantly lengthened in
      the anteroposterior dimension compared with contralateral glands (P < .001) and
      displaced anteriorly and inferiorly within the submandibular and submental
      spaces. Enhancement patterns of the transferred submandibular glands varied,
      depending on the time of imaging relative to the operation and radiation therapy.
      Submandibular gland transfer was acknowledged in the postoperative report in 7/11
      cases. Errors in interpretation were present in 2/11 reports. CONCLUSIONS: After
      the submandibular gland transfer procedure, the submandibular and submental
      spaces lose their symmetric appearances as the transferred submandibular glands
      become lengthened and located more anteriorly and inferiorly, with variable
      enhancement characteristics. Familiarity with the postsurgical appearance of the
      transferred submandibular glands is key to accurate imaging interpretation.

PMID- 29599173
TI  - Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the
      Tubridge Flow Diverter: A Multicenter, Randomized, Controlled Clinical Trial
      (PARAT).
AB  - BACKGROUND AND PURPOSE: Although flow diverters have been reported with favorable
      clinical and angiographic outcomes in various literatures, randomized trials
      determining their true effectiveness and safety are still in lack. The Parent
      Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge
      Flow Diverter (PARAT) trial was designed to evaluate the safety and efficacy of
      the Tubridge flow diverter in the treatment of large or giant aneurysms in
      comparison with Enterprise stent-assisted coiling. MATERIALS AND METHODS: This
      prospective, multicenter, randomized trial was conducted at 12 hospitals
      throughout China. Enrolled adults with unruptured large/giant intracranial
      aneurysms were randomly assigned (1:1) to receive either Enterprise stent
      assisted coiling or Tubridge flow diverter implantation. The primary end point
      was complete occlusion at 6-month follow-up, while secondary end points included
      technical success, mortality, target vessel-related stroke, aneurysm bleeding, in
      stent stenosis, parent artery occlusion, and the frequency of all adverse events.
      RESULTS: Among 185 enrolled subjects, 41 withdrew before procedure initiation.
      Overall, 82 subjects underwent Tubridge implantation, and 62 subjects were
      primarily treated with stent-assisted coiling. The results of 6-month follow-up
      imaging included complete occlusion rates of 75.34% versus 24.53% for the
      Tubridge and stent-assisted coiling groups, respectively, with a calculated
      common odds ratio of 9.4 (95% confidence interval, 4.14-21.38; P < .001). There
      was a higher, nonsignificant frequency of complications for Tubridge subjects.
      Multivariate analysis showed a decreased stroke rate at the primary
      investigational site, with a marginal P value (P = .051). CONCLUSIONS: This trial
      showed an obviously higher rate of large and giant aneurysm obliteration with the
      Tubridge FD over Enterprise stent-assisted coiling. However, this higher
      obliteration rate came at the cost of a nonsignificantly higher rate of
      complications. Investigational site comparisons suggested that a learning curve
      for flow-diverter implantation should be recognized and factored into trial
      designs.

PMID- 29599174
TI  - An Update on the Adjunctive Neurovascular Support of Wide-Neck Aneurysm
      Embolization and Reconstruction Trial: 1-Year Safety and Angiographic Results.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of the PulseRider for the
      treatment of wide-neck, bifurcation aneurysms at the basilar and carotid terminus
      locations were studied in a prospective trial, the Adjunctive Neurovascular
      Support of Wide-Neck Aneurysm Embolization and Reconstruction (ANSWER) trial,
      reporting on initial 6-month angiographic and clinical results. This report
      provides insight into the longer term durability and safety with 12-month data.
      MATERIALS AND METHODS: Aneurysms treated with the PulseRider among enrolled sites
      were prospectively studied. Updated 12-month data on clinical and imaging end
      points are included. RESULTS: Thirty-four patients were enrolled (29 women, 5
      men) with a mean age of 60.9 years. The mean aneurysm height ranged from 2.4 to
      15.9 mm with a mean neck size of 5.2 mm (range, 2.3-11.6 mm). At 1 year, there
      were no device migrations or symptomatic in-stent stenoses. Raymond-Roy I
      occlusion was achieved in 53% of cases at the time of treatment and progressed to
      61% and 67% at 6 and 12 months, respectively. Adequate occlusion (Raymond-Roy
      I/II) progressed from 88% at 6 months to 90% at 12 months. No recanalizations
      were observed. There was 1 delayed ischemic event. Good outcome (mRS 0-2) was
      achieved in 90% of patients. CONCLUSIONS: The updated 1-year results from the
      ANSWER trial demonstrate aneurysm stability and an acceptable safety profile for
      aneurysms treated at the basilar apex and carotid terminus. Prospective data from
      a larger set of aneurysms treated at other locations are required to assess how
      treatment with PulseRider compares with alternatives for treating wide-neck
      bifurcation aneurysms.

PMID- 29599175
TI  - Mild encephalitis with reversible splenial (MERS) lesion syndrome due to
      influenza B virus.
AB  - We describe a 16-year-old boy with mild encephalitis with reversible lesions in
      the white matter and splenium of corpus callosum as a complication of an
      influenza B virus infection. Although more common in Asiatic children, it can
      also occur in Caucasian children and adults. There are several possible causes,
      including metabolic disorders, hypertension and infection, and the prognosis is
      usually good, even without treatment.

PMID- 29599176
TI  - H3K4 Methylation Dependent and Independent Chromatin Regulation by JHD2 and SET1
      in Budding Yeast.
AB  - Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me)
      through their opposing methyltransferase and demethylase activities in the
      budding yeast Saccharomyces cerevisiae H3K4me associates with actively
      transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate
      gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act
      solely through H3K4me. Relevantly, Set1 methylates lysine residues in the
      kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog
      suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We
      interrogated genetic interactions of JHD2 and SET1 with essential genes involved
      in varied aspects of the transcription cycle. Our findings implicate JHD2 in
      genetic inhibition of the histone chaperone complexes Spt16-Pob3 (FACT) and Spt6
      Spn1 This targeted screen also revealed that JHD2 inhibits the Nrd1-Nab3-Sen1
      (NNS) transcription termination complex. We find that while Jhd2's impact on
      these transcription regulatory complexes likely acts via H3K4me, Set1 governs the
      roles of FACT and NNS through opposing H3K4-dependent and -independent functions.
      We also identify diametrically opposing consequences for mutation of H3K4 to
      alanine or arginine, illuminating that caution must be taken in interpreting
      histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest
      an H3K4me-centric mode of Spt6-Spn1 regulation by JHD2 and SET1 Chromatin
      immunoprecipitation and transcript quantification experiments show that Jhd2
      opposes the positioning of a Spt6-deposited nucleosome near the transcription
      start site of SER3, a Spt6-Spn1 regulated gene, leading to hyper-induction of
      SER3 In addition to confirming and extending an emerging role for Jhd2 in the
      control of nucleosome occupancy near transcription start sites, our findings
      suggest some of the chromatin regulatory functions of Set1 are independent of
      H3K4 methylation.

PMID- 29599179
TI  - Response to Brodersen et al' s 'Overdiagnosis: what it is and what it isn't'.

PMID- 29599177
TI  - Teleost Fish-Specific Preferential Retention of Pigmentation Gene-Containing
      Families After Whole Genome Duplications in Vertebrates.
AB  - Vertebrate pigmentation is a highly diverse trait mainly determined by neural
      crest cell derivatives. It has been suggested that two rounds (1R/2R) of whole
      genome duplications (WGDs) at the basis of vertebrates allowed changes in gene
      regulation associated with neural crest evolution. Subsequently, the teleost fish
      lineage experienced other WGDs, including the teleost-specific Ts3R before
      teleost radiation and the more recent Ss4R at the basis of salmonids. As the
      teleost lineage harbors the highest number of pigment cell types and pigmentation
      diversity in vertebrates, WGDs might have contributed to the evolution and
      diversification of the pigmentation gene repertoire in teleosts. We have compared
      the impact of the basal vertebrate 1R/2R duplications with that of the teleost
      specific Ts3R and salmonid-specific Ss4R WGDs on 181 gene families containing
      genes involved in pigmentation. We show that pigmentation genes (PGs) have been
      globally more frequently retained as duplicates than other genes after Ts3R and
      Ss4R but not after the early 1R/2R. This is also true for non-pigmentary paralogs
      of PGs, suggesting that the function in pigmentation is not the sole key driver
      of gene retention after WGDs. On the long-term, specific categories of PGs have
      been repeatedly preferentially retained after ancient 1R/2R and Ts3R WGDs,
      possibly linked to the molecular nature of their proteins (e.g., DNA binding
      transcriptional regulators) and their central position in protein-protein
      interaction networks. Taken together, our results support a major role of WGDs in
      the diversification of the pigmentation gene repertoire in the teleost lineage,
      with a possible link with the diversity of pigment cell lineages observed in
      these animals compared to other vertebrates.

PMID- 29599180
TI  - Expanding epidemiology and biostatistics curricula in undergraduate medical
      education to promote evidence-based practice.

PMID- 29599178
TI  - Phospholipid-flipping activity of P4-ATPase drives membrane curvature.
AB  - P4-ATPases are phospholipid flippases that translocate phospholipids from the
      exoplasmic/luminal to the cytoplasmic leaflet of biological membranes. All P4
      ATPases in yeast and some in other organisms are required for membrane
      trafficking; therefore, changes in the transbilayer lipid composition induced by
      flippases are thought to be crucial for membrane deformation. However, it is
      poorly understood whether the phospholipid-flipping activity of P4-ATPases can
      promote membrane deformation. In this study, we assessed membrane deformation
      induced by flippase activity via monitoring the extent of membrane tubulation
      using a system that allows inducible recruitment of Bin/amphiphysin/Rvs (BAR)
      domains to the plasma membrane (PM). Enhanced phosphatidylcholine-flippase
      activity at the PM due to expression of ATP10A, a member of the P4-ATPase family,
      promoted membrane tubulation upon recruitment of BAR domains to the PM This is
      the important evidence that changes in the transbilayer lipid composition induced
      by P4-ATPases can deform biological membranes.

PMID- 29599181
TI  - Proton pump inhibitor therapy after Helicobacter pylori eradication may increase
      the risk of gastric cancer.

PMID- 29599182
TI  - Short-term cancer risks associated with oral contraceptives are balanced by
      longer term benefits.

PMID- 29599183
TI  - Embolization through the thyrocervical trunk: vascular anatomy, variants, and a
      case series.
AB  - BACKGROUND AND PURPOSE: The thyrocervical trunk (TCT) is the second ascending
      branch of the subclavian artery. It is considered a 'border territory' between
      interventional vascular radiology and interventional neuroradiology because it
      gives rise to branches both cervical and to the upper limbs. We describe the TCT
      branches anatomy, the most frequent variants, and expose eight endovascular
      procedures performed through the thyrocervical trunk. METHODS: A retrospective
      review of all the interventional radiology procedures carried out through the TCT
      in our tertiary care center from August 2014 to January 2017 is presented.
      RESULTS: A total of eight endovascular procedures through the TCT including six
      preoperative embolizations: three paragangliomas, a cervical vertebral
      metastasis, a cervical vertebral aneurysmal bone cyst, and a very rare case of
      nerve root extradural cervical hemangioblastoma, as well as two emergency
      embolizations: a patient with a cervical traumatic active bleeding hematoma and a
      recurrent hemoptysis in a single ventricle patient. CONCLUSIONS: A correct
      knowledge of the vascular anatomy, anatomical variants, and anastomosis
      (especially with the anterior spinal artery) of the TCT is essential for a safe
      embolization, both preoperatively and on an emergency basis. In cases of
      recurrent hemoptysis and severe lower-neck injuries, the TCT should always be
      reviewed.

PMID- 29599184
TI  - Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological
      methods.
AB  - Diagnosing pulmonary tuberculosis (TB) may be delayed until culture results
      become available.We ascertained the accuracy of a stepwise diagnostic algorithm
      for the rapid diagnosis of pulmonary TB by GeneXpert from sputum and/or
      bronchoalveolar lavage (BAL) followed by a Mycobacterium tuberculosis-specific
      BAL ELISPOT assay in patients with a suspected diagnosis of pulmonary TB at a
      clinical referral centre in Germany.Among 166 patients with a presumptive
      diagnosis of pulmonary TB, 81 cases were confirmed by M. tuberculosis culture
      from sputum and/or BAL. In 66 out of 81 (81.5%) cases, patients initially had M.
      tuberculosis detected by GeneXpert from sputum; in addition, six out of 81 (7.4%)
      cases were diagnosed by GeneXpert on BAL fluid (together 72 out of 81 (88.9%)
      patients). Out of the remaining nine patients with negative GeneXpert results
      from sputum and BAL, BAL ELISPOT identified eight patients with culture-confirmed
      TB correctly (median time to culture positivity 26 days). At a cut-off of >4000
      early secretory antigenic target-6- or culture filtrate protein-10-specific
      interferon-gamma-producing lymphocytes per 1 000 0000 lymphocytes, the
      specificity of the BAL ELISPOT for active TB was 97%.In low TB incidence
      countries, nearly all patients with active pulmonary TB can be identified within
      the first few days of clinical presentation using a stepwise strategy with
      GeneXpert and BAL ELISPOT.

PMID- 29599185
TI  - Efficacy and costs of telehealth for the management of COPD: the PROMETE II
      trial.

PMID- 29599186
TI  - In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart
      disease.
AB  - The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD).
      The current classification system for definitions of PH-LHD is under review. We
      therefore performed prospective in-depth invasive haemodynamic phenotyping in
      order to assess the site of increased pulmonary vascular resistance (PVR) in PH
      LHD subsets.Based on pulmonary artery occlusion waveforms yielding an estimate of
      the effective capillary pressure, we partitioned PVR in larger arterial (Rup,
      upstream resistance) and small arterial plus venous components (Rds, downstream
      resistance). In the case of small vessel disease, Rup decreases and Rds
      increases. Inhaled nitric oxide (NO) testing was used to assess acute
      vasoreactivity.Right ventricular afterload (PVR, pulmonary arterial compliance
      and effective arterial elastance) was significantly higher in combined post- and
      pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH,
      n=20). Right ventricular afterload decreased during inhalation of NO in Cpc-PH
      and idiopathic pulmonary arterial hypertension (n=31), but remained unchanged in
      Ipc-PH. Rup was similar in Cpc-PH (66.8+/-10.8%) and idiopathic pulmonary
      arterial hypertension (65.0+/-12.2%; p=0.530) suggesting small vessel disease,
      but significantly higher in Ipc-PH (96.5+/-4.5%; p<0.001) suggesting upstream
      transmission of elevated left atrial pressure.Right ventricular afterload is
      driven by elevated left atrial pressure in Ipc-PH and is further increased by
      elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to inhaled NO.
      Our data support current definitions of PH-LHD subsets.

PMID- 29599187
TI  - The in vitro effect of nebulised hypertonic saline on human bronchial epithelium.
AB  - Inhaled hypertonic saline (HS) is an effective therapy for muco-obstructive lung
      diseases. However, the mechanism of action and principles pertinent to HS
      administration remain unclear.An in vitro system aerosolised HS to epithelial
      cells at rates comparable to in vivo conditions. Airway surface liquid (ASL)
      volume and cell height responses were measured by confocal microscopy under
      normal and hyperconcentrated mucus states.Aerosolised HS produced a rapid
      increase in ASL height and decrease in cell height. Added ASL volume was quickly
      reabsorbed following termination of nebulisation, although cell height did not
      recover within the same time frame. ASL volume responses to repeated HS
      administrations were blunted, but could be restored by a hypotonic saline bolus
      interposed between HS administrations. HS-induced ASL hydration was prolonged
      with hyperconcentrated mucus on the airway surface, with more modest reductions
      in cell volume.Aerosolised HS produced osmotically induced increases in ASL
      height that were limited by active sodium absorption and cell volume-induced
      reductions in cell water permeability. Mucus on airway surfaces prolonged the
      effect of HS via mucus-dependent osmotic forces, suggesting that the duration of
      action of HS is increased in patients with hyperconcentrated mucus.

PMID- 29599188
TI  - Prognostic impact of copeptin in pulmonary embolism: a multicentre validation
      study.
AB  - To externally validate the prognostic impact of copeptin, either alone or
      integrated in risk stratification models, in pulmonary embolism (PE), we
      performed a post hoc analysis of 843 normotensive PE patients prospectively
      included in three European cohorts.Within the first 30 days, 21 patients (2.5%,
      95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to
      PE. Patients with copeptin >=24 pmol.L-1 had a 6.3-fold increased risk for an
      adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE
      related death (95% CI 2.3-25.6, p=0.001). Risk classification according to the
      2014 European Society of Cardiology (ESC) guideline algorithm identified 248
      intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of
      adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on
      high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and
      copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95%
      CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at
      higher risk was even better when copeptin was measured on top of the 2014 ESC
      algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6
      27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest
      risk group versus all other risk groups). This identified 85 patients (10.1%)
      with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4
      16.2) at risk of PE-related deaths.Copeptin improves risk stratification of
      normotensive PE patients, especially when identifying patients with an increased
      risk of an adverse outcome.

PMID- 29599189
TI  - Pharmacokinetics of tuberculosis drugs in HIV-infected patients from Irkutsk,
      Russian Federation: redefining drug activity.

PMID- 29599190
TI  - A Structured Workflow for Mapping Human Sin3 Histone Deacetylase Complex
      Interactions Using Halo-MudPIT Affinity-Purification Mass Spectrometry.
AB  - Although a variety of affinity purification mass spectrometry (AP-MS) strategies
      have been used to investigate complex interactions, many of these are susceptible
      to artifacts because of substantial overexpression of the exogenously expressed
      bait protein. Here we present a logical and systematic workflow that uses the
      multifunctional Halo tag to assess the correct localization and behavior of
      tagged subunits of the Sin3 histone deacetylase complex prior to further AP-MS
      analysis. Using this workflow, we modified our tagging/expression strategy with
      21.7% of the tagged bait proteins that we constructed, allowing us to quickly
      develop validated reagents. Specifically, we apply the workflow to map
      interactions between stably expressed versions of the Sin3 subunits SUDS3, SAP30,
      or SAP30L and other cellular proteins. Here we show that the SAP30 and SAP30L
      paralogues strongly associate with the core Sin3 complex, but SAP30L has unique
      associations with the proteasome and the myelin sheath. Next, we demonstrate an
      advancement of the complex NSAF (cNSAF) approach, in which normalization to the
      scaffold protein SIN3A accounts for variations in the proportion of each bait
      capturing Sin3 complexes and allows a comparison among different baits capturing
      the same protein complex. This analysis reveals that although the Sin3 subunit
      SUDS3 appears to be used in both SIN3A and SIN3B based complexes, the SAP30
      subunit is not used in SIN3B based complexes. Intriguingly, we do not detect the
      Sin3 subunits SAP18 and SAP25 among the 128 high-confidence interactions
      identified, suggesting that these subunits may not be common to all versions of
      the Sin3 complex in human cells. This workflow provides the framework for
      building validated reagents to assemble quantitative interaction networks for
      chromatin remodeling complexes and provides novel insights into focused protein
      interaction networks.

PMID- 29599191
TI  - AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response
      Signaling Through Facilitating CReP/PPP1R15B Degradation.
AB  - The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or
      misfolded proteins in diverse cellular stress response pathways. Resolving the
      complexity of its interactions with partner and substrate proteins and
      understanding its links to stress signaling is therefore a major challenge. Here,
      we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify
      proteins that specifically interact with the substrate-trapping mutant, p97
      E578Q. AP-SWATH identified differential interactions over a large detection range
      from abundant p97 cofactors to pathway-specific partners and individual ligases
      such as RNF185 and MUL1 that were trapped in p97-E578Q complexes. In addition, we
      identified various substrate proteins and candidates including the PP1 regulator
      CReP/PPP1R15B that dephosphorylates eIF2alpha and thus counteracts attenuation of
      translation by stress-kinases. We provide evidence that p97 with its Ufd1-Npl4
      adapter ensures rapid constitutive turnover and balanced levels of CReP in
      unperturbed cells. Moreover, we show that p97-mediated degradation, together with
      a reduction in CReP synthesis, is essential for timely stress-induced reduction
      of CReP levels and, consequently, for robust eIF2alpha phosphorylation to enforce
      the stress response. Thus, our results demonstrate that p97 not only facilitates
      bulk degradation of misfolded proteins upon stress, but also directly modulates
      the integrated stress response at the level of signaling.

PMID- 29599192
TI  - Imaging of nonlocal hot-electron energy dissipation via shot noise.
AB  - In modern microelectronic devices, hot electrons accelerate, scatter, and
      dissipate energy in nanoscale dimensions. Despite recent progress in
      nanothermometry, direct real-space mapping of hot-electron energy dissipation is
      challenging because existing techniques are restricted to probing the lattice
      rather than the electrons. We realize electronic nanothermometry by measuring
      local current fluctuations, or shot noise, associated with ultrafast hot-electron
      kinetic processes (~21 terahertz). Exploiting a scanning and contact-free
      tungsten tip as a local noise probe, we directly visualize hot-electron
      distributions before their thermal equilibration with the host gallium
      arsenide/aluminium gallium arsenide crystal lattice. With nanoconstriction
      devices, we reveal unexpected nonlocal energy dissipation at room temperature,
      which is reminiscent of ballistic transport of low-temperature quantum
      conductors.

PMID- 29599193
TI  - Pulmonary neuroendocrine cells amplify allergic asthma responses.
AB  - Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose
      function is poorly understood. Here we show that Ascl1-mutant mice that have no
      PNECs exhibit severely blunted mucosal type 2 response in models of allergic
      asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s)
      near airway branch points. PNECs act through calcitonin gene-related peptide
      (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition,
      PNECs act through the neurotransmitter gamma-aminobutyric acid (GABA) to induce
      goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1
      mutant airways restores both immune and goblet cell responses. In accordance,
      lungs from human asthmatics show increased PNECs. These findings demonstrate that
      the PNEC-ILC2 neuroimmunological modules function at airway branch points to
      amplify allergic asthma responses.

PMID- 29599196
TI  - Bawa-Garba granted Court of Appeal challenge against erasure ruling.

PMID- 29599194
TI  - Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity.
AB  - Activated immune cells undergo a metabolic switch to aerobic glycolysis akin to
      the Warburg effect, thereby presenting a potential therapeutic target in
      autoimmune disease. Dimethyl fumarate (DMF), a derivative of the Krebs cycle
      intermediate fumarate, is an immunomodulatory drug used to treat multiple
      sclerosis and psoriasis. Although its therapeutic mechanism remains uncertain,
      DMF covalently modifies cysteine residues in a process termed succination. We
      found that DMF succinates and inactivates the catalytic cysteine of the
      glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in mice and
      humans, both in vitro and in vivo. It thereby down-regulates aerobic glycolysis
      in activated myeloid and lymphoid cells, which mediates its anti-inflammatory
      effects. Our results provide mechanistic insight into immune modulation by DMF
      and represent a proof of concept that aerobic glycolysis is a therapeutic target
      in autoimmunity.

PMID- 29599195
TI  - 2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced
      thrombocytopenia.
AB  - Thrombocytopenia is a significant complication of chemotherapy and radiation
      therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of
      megakaryopoiesis. We have shown that PF4 levels are inversely related to steady
      state platelet counts, and to the duration and severity of chemotherapy- and
      radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies
      suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir
      platelet counts and shortening the time to platelet count recovery. We examined
      the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little
      anticoagulant effects, to neutralize PF4's effects on megakaryopoiesis. Using
      megakaryocyte colony assays and liquid cultures, we show that ODSH restored
      megakaryocyte proliferation in PF4-treated Cxcl4-/- murine and human CD34+
      derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared
      with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was
      examined for the effect on hematopoietic recovery demonstrating higher platelet
      count nadirs (9% +/- 5% treated vs 4% +/- 4% control) and significantly improved
      survival in treated animals (73% treated vs 36% control survival). Treatment with
      ODSH was able to reduce intramedullary free PF4 concentrations by
      immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by
      neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical
      trials in humans as an adjuvant to chemotherapy, may be an important, clinically
      relevant therapeutic for CIT and RIT.

PMID- 29599197
TI  - Telephone consultations.

PMID- 29599199
TI  - A lung full of Cheerios.

PMID- 29599198
TI  - Acceptance of Routine HIV Testing by Hospitalized Adolescents and Young Adults.
AB  - BACKGROUND AND OBJECTIVES: Youth carry a disproportionate burden of new HIV
      infections. With our study, we aimed to characterize HIV testing experiences
      among adolescents and young adults admitted to a children's hospital that is
      located in a high HIV-prevalent community and implemented routine HIV testing for
      all patients >=13 years of age. METHODS: A total of 120 patients aged 13 to 24
      years old who were admitted to our hospital and had a documented offer of routine
      HIV testing on admission were invited to complete a self-administered survey that
      asked about sex, race and/or ethnicity, HIV risk behaviors, and attitudes toward
      routine HIV testing in the hospital. Date of birth, admission diagnosis, and
      verification of HIV testing and results were collected by chart review. RESULTS:
      Study participants (N = 99) were 17.4 +/- 2.3 years old, 52% female, 47%
      Hispanic, and 29% African American. Additional characteristics include the
      following: 65% had previous sexual activity, 11% had a history of sexually
      transmitted infections, and 12% were worried about their risk for HIV. Forty
      seven percent of participants accepted HIV testing, with older patients (P < .01)
      and those reporting previous sexual activity (P < .01) and a previous HIV test (P
      < .01) being more likely to accept testing. A total of 96% of participants agreed
      that the hospital is a good place to offer HIV testing. CONCLUSIONS: Our findings
      support offering routine HIV testing to youth admitted to children's hospital.
      Given the high incidence of new and undiagnosed HIV infections among youth,
      additional venues for HIV testing are essential.

PMID- 29599200
TI  - The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a
      report from the prospective, International T-Cell Project.
AB  - This analysis explored factors influencing survival of patients with primary
      refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective
      International T-cell Project. We analyzed data from 1020 patients with newly
      diagnosed disease, enrolled between September 2006 and December 2015. Out of 937
      patients who received first-line treatment, 436 (47%) were identified as
      refractory and 197 (21%) as relapsed. Median time from the end of treatment to
      relapse was 8 months (range 2-73). Overall, 75 patients (8%) were consolidated
      with bone marrow transplantation, including 12 refractory and 22 relapsed
      patients. After a median follow up of 38 months (range 1-96 months) from
      documentation of refractory/relapsed disease, 440 patients had died. The median
      overall survival (OS) was 5.8 months; 3-year overall survival rates were 21% and
      28% for refractory and relapsed patients, respectively (P<0.001). Patients
      receiving or not salvage bone marrow transplantation had a 3-year survival of 48%
      and 18%, respectively (P<0.001). In a univariate Cox regression analysis,
      refractory disease was associated with a higher risk of death (HR=1.43, P=0.001),
      whereas late relapse (>12 months, HR 0.57, P=0.001) and salvage therapy with
      transplantation (HR=0.36, P<0.001) were associated with a better OS. No
      difference was found in OS with respect to histology. This study accurately
      reflects outcomes for patients treated according to standards of care worldwide.
      Results confirm that peripheral T-cell lymphomas patients had dismal outcome
      after relapse or progression. Patients with chemotherapy sensitive disease who
      relapsed after more than 12 months might benefit from consolidation bone marrow
      transplantation.

PMID- 29599201
TI  - The chromatin-remodeling factor CHD4 is required for maintenance of childhood
      acute myeloid leukemia.
AB  - Epigenetic alterations contribute to leukemogenesis in childhood acute myeloid
      leukemia and therefore are of interest for potential therapeutic strategies.
      Herein, we performed large-scale ribonucleic acid interference screens using
      small hairpin ribonucleic acids in acute myeloid leukemia cells and non
      transformed bone marrow cells to identify leukemia-specific dependencies. One of
      the target genes displaying the strongest effects on acute myeloid leukemia cell
      growth and less pronounced effects on nontransformed bone marrow cells, was the
      chromatin remodeling factor CHD4 Using ribonucleic acid interference and CRISPR
      Cas9 approaches, we showed that CHD4 was essential for cell growth of leukemic
      cells in vitro and in vivo Loss of function of CHD4 in acute myeloid leukemia
      cells caused an arrest in the G0 phase of the cell cycle as well as
      downregulation of MYC and its target genes involved in cell cycle progression.
      Importantly, we found that inhibition of CHD4 conferred anti-leukemic effects on
      primary childhood acute myeloid leukemia cells and prevented disease progression
      in a patient-derived xenograft model. Conversely, CHD4 was not required for
      growth of normal hematopoietic cells. Taken together, our results identified CHD4
      as a potential therapeutic target in childhood acute myeloid leukemia.

PMID- 29599202
TI  - MYD88 mutated and wild-type Waldenstrom's Macroglobulinemia: characterization of
      chromosome 6q gene losses and their mutual exclusivity with mutations in CXCR4.

PMID- 29599203
TI  - Successful treatment of disseminated Rosai-Dorfman disease with siltuximab.

PMID- 29599204
TI  - Late effects after hematopoietic stem cell transplantation for beta-thalassemia
      major: the French national experience.
AB  - In this retrospective study, we evaluate long-term complications in nearly all
      beta-thalassemia-major patients who successfully received allogeneic
      hematopoietic stem cell transplantation in France. Ninety-nine patients were
      analyzed with a median age of 5.9 years at transplantation. The median duration
      of clinical follow up was 12 years. All conditioning regimens were myeloablative,
      most were based on busulfan combined with cyclophosphamide, and more than 90% of
      patients underwent a transplant from a matched sibling donor. After
      transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and
      2% heart failure. Hypogonadism was present in 56% of females and 14% of males.
      Female patients who went on to normal puberty after transplant were significantly
      younger at transplantation than those who experienced delayed puberty (median age
      2.5 vs 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or
      older and 2 other patients became pregnant following oocyte donation. In addition
      to patient's age and higher serum ferritin levels at transplantation, time
      elapsed since transplant was significantly associated with decreased height
      growth in multivariate analysis. Weight growth increased after transplantation
      particularly in females, 36% of adults being overweight at last evaluation. A
      comprehensive long-term monitoring, especially of endocrine late effects, is
      required after hematopoietic stem cell transplantation for thalassemia.

PMID- 29599207
TI  - Rise in GPs taking early retirement.

PMID- 29599205
TI  - Recurring mutations in RPL15 are linked to hydrops fetalis and treatment
      independence in Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure disorder
      linked predominantly to ribosomal protein gene mutations. Here the European DBA
      consortium reports novel mutations identified in the RPL15 gene in 6 unrelated
      individuals diagnosed with DBA. Although point mutations have not been previously
      reported for RPL15, we identified 4 individuals with truncating mutations
      p.Tyr81* (in 3 of 4) and p.Gln29*, and 2 with missense variants p.Leu10Pro and
      p.Lys153Thr. Notably, 75% (3 of 4) of truncating mutation carriers manifested
      with severe hydrops fetalis and required intrauterine transfusions. Even more
      remarkable is the observation that the 3 carriers of p.Tyr81* mutation became
      treatment-independent between four and 16 months of life and maintained normal
      blood counts until their last follow up. Genetic reversion at the DNA level as a
      potential mechanism of remission was not observed in our patients. In vitro
      studies revealed that cells carrying RPL15 mutations have pre-rRNA processing
      defects, reduced 60S ribosomal subunit formation, and severe proliferation
      defects. Red cell culture assays of RPL15-mutated primary erythroblast cells also
      showed a severe reduction in cell proliferation, delayed erythroid
      differentiation, elevated TP53 activity, and increased apoptosis. This study
      identifies a novel subgroup of DBA with mutations in the RPL15 gene with an
      unexpected high rate of hydrops fetalis and spontaneous, long-lasting remission.

PMID- 29599206
TI  - Impact of hydroxycarbamide and interferon-alpha on red cell adhesion and membrane
      protein expression in polycythemia vera.
AB  - Polycythemia vera is a chronic myeloproliferative neoplasm characterized by the
      JAK2V617F mutation, elevated blood cell counts and a high risk of thrombosis.
      Although the red cell lineage is primarily affected by JAK2V617F, the impact of
      mutated JAK2 on circulating red blood cells is poorly documented. Recently, we
      showed that in polycythemia vera, erythrocytes had abnormal expression of several
      proteins including Lu/BCAM adhesion molecule and proteins from the endoplasmic
      reticulum, mainly calreticulin and calnexin. Here we investigated the effects of
      hydroxycarbamide and interferon-alpha treatments on the expression of erythroid
      membrane proteins in a cohort of 53 patients. Surprisingly, while both drugs
      tended to normalize calreticulin expression, proteomics analysis showed that
      hydroxycarbamide deregulated the expression of 53 proteins in red cell ghosts,
      with overexpression and downregulation of 37 and 16 proteins, respectively.
      Within over-expressed proteins, hydroxycarbamide was found to enhance the
      expression of adhesion molecules such as Lu/BCAM and CD147, while interferon
      alpha did not. In addition, we found that hydroxycarbamide increased Lu/BCAM
      phosphorylation and exacerbated red cell adhesion to its ligand laminin. Our
      study reveals unexpected adverse effects of hydroxycarbamide on red cell
      physiology in polycythemia vera and provides new insights into the effects of
      this molecule on gene regulation and protein recycling or maturation during
      erythroid differentiation. Furthermore, our study shows deregulation of Lu/BCAM
      and CD147 that are two ubiquitously expressed proteins linked to progression of
      solid tumors, paving the way for future studies to address the role of
      hydroxycarbamide in tissues other than blood cells in myeloproliferative
      neoplasms.

PMID- 29599209
TI  - Optimal ventilator strategies for trauma-related ARDS.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) was first described in the
      1960s and has become a major area of research due to the mortality and morbidity
      associated with it. ARDS is currently defined using the Berlin Consensus;
      however, this is not wholly applicable for trauma-related ARDS. METHODS: A
      systematic review of the literature was undertaken using the Preferred Reporting
      for Systematic Reviews and Meta Analyses methodology. The Ovid Medline, Web of
      Science and PubMed online databases were interrogated for papers published
      between 1 January 1995 and 31 December 2017. RESULTS: The literature search
      yielded a total of 64 papers that fulfilled the search criteria. CONCLUSIONS:
      Despite decades of dedicated research into different treatment modalities, ARDS
      continues to carry a high burden of mortality. The ARDS definitions laid out in
      the Berlin consensus are not entirely suited to trauma. While trauma-related ARDS
      represents a small portion of the available research, the evidence continues to
      favour low tidal volume ventilation as the benchmark for current practice.
      Positive end expiratory ventilation and airway pressure release ventilation in
      trauma cohorts may be beneficial; however, the evidence to date does not show
      this.

PMID- 29599208
TI  - Lgr5+ intestinal stem cells reside in an unlicensed G1 phase.
AB  - During late mitosis and the early G1 phase, the origins of replication are
      licensed by binding to double hexamers of MCM2-7. In this study, we investigated
      how licensing and proliferative commitment are coupled in the epithelium of the
      small intestine. We developed a method for identifying cells in intact tissue
      containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying
      compartment had no DNA-bound MCM2-7, but still expressed the MCM2-7 protein,
      suggesting that licensing is inhibited immediately upon differentiation.
      Strikingly, we found most proliferative Lgr5+ stem cells are in an unlicensed
      state. This suggests that the elongated cell-cycle of intestinal stem cells is
      caused by an increased G1 length, characterized by dormant periods with
      unlicensed origins. Significantly, the unlicensed state is lost in Apc-mutant
      epithelium, which lacks a functional restriction point, causing licensing
      immediately upon G1 entry. We propose that the unlicensed G1 phase of intestinal
      stem cells creates a temporal window when proliferative fate decisions can be
      made.

PMID- 29599210
TI  - Safe burn excision prior to military repatriation: an achievable goal?
AB  - Burn excision is the gold standard treatment for full thickness and some deep
      partial thickness burns. Early burn excision (24-96 hours) has been shown to
      improve patient outcomes. However, in the military setting, transporting the
      patient to a centre which can provide this procedure can be delayed. Especially
      as control of airspace in the future may be hampered due to the political
      landscape. For this reason, focus on how to achieve safer burn excision prior to
      repatriation should be addressed. This paper considers the barriers to early burn
      excision in the military setting and offers potential solutions for the future.

PMID- 29599211
TI  - Experimental Right Ventricular Hypertension Induces Regional beta1-Integrin
      Mediated Transduction of Hypertrophic and Profibrotic Right and Left Ventricular
      Signaling.
AB  - BACKGROUND: Development of right ventricular (RV) hypertension eventually
      contributes to RV and left ventricular (LV) myocardial fibrosis and dysfunction.
      The molecular mechanisms are not fully elucidated. METHODS AND RESULTS: Pulmonary
      artery banding was used to induce RV hypertension in rats in vivo. Then, we
      evaluated cardiac function and regional remodeling 6 weeks after pulmonary artery
      banding. To further elucidate mechanisms responsible for regional cardiac
      remodeling, we also mimicked RV hypertensive stress by cyclic mechanical
      stretching applied to confluent cultures of cardiac fibroblasts, isolated from
      the RV free wall, septal hinge points, and LV free wall. Echocardiography and
      catheter evaluation demonstrated that rats in the pulmonary artery banding group
      developed RV hypertension with leftward septal displacement, LV compression, and
      increased LV end-diastolic pressures. Picrosirius red staining indicated that
      pulmonary artery banding induced marked RV fibrosis and dysfunction, with
      prominent fibrosis and elastin deposition at the septal hinge points but less LV
      fibrosis. These changes were associated with proportionally increased expressions
      of integrin-beta1 and profibrotic signaling proteins, including phosphorylated
      Smad2/3 and transforming growth factor-beta1. Moreover, mechanically stretched
      fibroblasts also expressed significantly increased levels of alpha-smooth muscle
      actin, integrin-beta1, transforming growth factor-beta1, collagen I deposition,
      and wrinkle formation on gel assays, consistent with myofibroblast
      transformation. These changes were not observed in parallel cultures of
      mechanically stretched fibroblasts, preincubated with the integrin inhibitor (BTT
      3033). CONCLUSIONS: Experimentally induced RV hypertension triggers regional RV,
      hinge-point, and LV integrin beta1-dependent mechanotransduction signaling
      pathways that eventually trigger myocardial fibrosis via transforming growth
      factor-beta1 signaling. Reduced LV fibrosis and preserved global function,
      despite geometrical and pressure aberrations, suggest a possible elastin-mediated
      protective mechanism at the septal hinge points.

PMID- 29599212
TI  - Is BMI the best measure of obesity?

PMID- 29599214
TI  - Response to Comment on "Enhanced water permeability and tunable ion selectivity
      in subnanometer carbon nanotube porins".
AB  - Horner and Pohl argue that high water transport rates reported for carbon
      nanotube porins (CNTPs) originate from leakage at the nanotube-bilayer interface.
      Our results and new experimental evidence are consistent with transport through
      the nanotube pores and rule out a defect-mediated transport mechanism.
      Mechanistic origins of the high Arrhenius factor that we reported for narrow
      CNTPs at pH 8 require further investigation.

PMID- 29599215
TI  - Comment on "Enhanced water permeability and tunable ion selectivity in
      subnanometer carbon nanotube porins".
AB  - Tunuguntla et al (Reports, 25 August 2017, p. 792) report that permeation of
      single-file water occurs faster through carbon nanotubes than through aquaporins.
      We show that this conclusion violates fundamental thermodynamic laws: Because of
      its much lower activation energy, aquaporin-mediated water transport must be
      orders of magnitude faster. Leakage at the nanotube-membrane interface may
      explain the discrepancy.

PMID- 29599213
TI  - Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory
      enhancing molecule.
AB  - Regulation by the integrated stress response (ISR) converges on the
      phosphorylation of translation initiation factor eIF2 in response to a variety of
      stresses. Phosphorylation converts eIF2 from a substrate to a competitive
      inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby
      inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects
      of eIF2 phosphorylation, and in rodents it enhances cognition and corrects
      cognitive deficits after brain injury. To determine its mechanism of action, we
      solved an atomic-resolution structure of ISRIB bound in a deep cleft within
      decameric human eIF2B by cryo-electron microscopy. Formation of fully active,
      decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric
      subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry
      interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B
      activity that tunes translation during the ISR and that can be further modulated
      by ISRIB.

PMID- 29599216
TI  - Keeping science honest.

PMID- 29599217
TI  - News at a glance.

PMID- 29599218
TI  - Congress gives science a record funding boost.

PMID- 29599219
TI  - U.K. trials of airway transplants are in limbo.

PMID- 29599220
TI  - U.S. blames 'massive' hack of research data on Iran.

PMID- 29599221
TI  - Meteorite divide points to solar system chaos.

PMID- 29599222
TI  - X-ray 'ghost images' could cut radiation doses.

PMID- 29599223
TI  - New missions aim to make a short list of exo-Earths.

PMID- 29599224
TI  - Putting immune cells on a diet.

PMID- 29599225
TI  - Change is key to frog survival.

PMID- 29599226
TI  - Natural killers join the fight against cancer.

PMID- 29599227
TI  - Making room for new memories.

PMID- 29599228
TI  - Li metal battery, heal thyself.

PMID- 29599229
TI  - Force matters in hospital-acquired infections.

PMID- 29599231
TI  - Mashing up metals with carbothermal shock.

PMID- 29599230
TI  - Neuronal-immune system cross-talk in homeostasis.

PMID- 29599232
TI  - Anatomy of STEM teaching in North American universities.

PMID- 29599233
TI  - Mining threatens Colombian ecosystems.

PMID- 29599234
TI  - Ocean deoxygenation: Time for action.

PMID- 29599235
TI  - A bound reaction intermediate sheds light on the mechanism of nitrogenase.
AB  - Reduction of N2 by nitrogenases occurs at an organometallic iron cofactor that
      commonly also contains either molybdenum or vanadium. The well-characterized
      resting state of the cofactor does not bind substrate, so its mode of action
      remains enigmatic. Carbon monoxide was recently found to replace a bridging
      sulfide, but the mechanistic relevance was unclear. Here we report the structural
      analysis of vanadium nitrogenase with a bound intermediate, interpreted as a MU2
      bridging, protonated nitrogen that implies the site and mode of substrate binding
      to the cofactor. Binding results in a flip of amino acid glutamine 176, which
      hydrogen-bonds the ligand and creates a holding position for the displaced
      sulfide. The intermediate likely represents state E6 or E7 of the Thorneley-Lowe
      model and provides clues to the remainder of the catalytic cycle.

PMID- 29599236
TI  - Carbothermal shock synthesis of high-entropy-alloy nanoparticles.
AB  - The controllable incorporation of multiple immiscible elements into a single
      nanoparticle merits untold scientific and technological potential, yet remains a
      challenge using conventional synthetic techniques. We present a general route for
      alloying up to eight dissimilar elements into single-phase solid-solution
      nanoparticles, referred to as high-entropy-alloy nanoparticles (HEA-NPs), by
      thermally shocking precursor metal salt mixtures loaded onto carbon supports
      [temperature ~2000 kelvin (K), 55-millisecond duration, rate of ~105 K per
      second]. We synthesized a wide range of multicomponent nanoparticles with a
      desired chemistry (composition), size, and phase (solid solution, phase
      separated) by controlling the carbothermal shock (CTS) parameters (substrate,
      temperature, shock duration, and heating/cooling rate). To prove utility, we
      synthesized quinary HEA-NPs as ammonia oxidation catalysts with ~100% conversion
      and >99% nitrogen oxide selectivity over prolonged operations.

PMID- 29599237
TI  - Adaptive infrared-reflecting systems inspired by cephalopods.
AB  - Materials and systems that statically reflect radiation in the infrared region of
      the electromagnetic spectrum underpin the performance of many entrenched
      technologies, including building insulation, energy-conserving windows,
      spacecraft components, electronics shielding, container packaging, protective
      clothing, and camouflage platforms. The development of their adaptive variants,
      in which the infrared-reflecting properties dynamically change in response to
      external stimuli, has emerged as an important unmet scientific challenge. By
      drawing inspiration from cephalopod skin, we developed adaptive infrared
      reflecting platforms that feature a simple actuation mechanism, low working
      temperature, tunable spectral range, weak angular dependence, fast response,
      stability to repeated cycling, amenability to patterning and multiplexing,
      autonomous operation, robust mechanical properties, and straightforward
      manufacturability. Our findings may open opportunities for infrared camouflage
      and other technologies that regulate infrared radiation.

PMID- 29599238
TI  - Activation of olefins via asymmetric Bronsted acid catalysis.
AB  - The activation of olefins for asymmetric chemical synthesis traditionally relies
      on transition metal catalysts. In contrast, biological enzymes with Bronsted
      acidic sites of appropriate strength can protonate olefins and thereby generate
      carbocations that ultimately react to form natural products. Although chemists
      have recently designed chiral Bronsted acid catalysts to activate imines and
      carbonyl compounds, mimicking these enzymes to protonate simple olefins that then
      engage in asymmetric catalytic reactions has remained a substantial synthetic
      challenge. Here, we show that a class of confined and strong chiral Bronsted
      acids enables the catalytic asymmetric intramolecular hydroalkoxylation of
      unbiased olefins. The methodology gives rapid access to biologically active 1,1
      disubstituted tetrahydrofurans, including (-)-Boivinianin A.

PMID- 29599239
TI  - Nanofluidic rocking Brownian motors.
AB  - Control and transport of nanoscale objects in fluids is challenging because of
      the unfavorable scaling of most interaction mechanisms to small length scales. We
      designed energy landscapes for nanoparticles by accurately shaping the geometry
      of a nanofluidic slit and exploiting the electrostatic interaction between like
      charged particles and walls. Directed transport was performed by combining
      asymmetric potentials with an oscillating electric field to achieve a rocking
      Brownian motor. Using gold spheres 60 nanometers in diameter, we investigated the
      physics of the motor with high spatiotemporal resolution, enabling a parameter
      free comparison with theory. We fabricated a sorting device that separates 60-
      and 100-nanometer particles in opposing directions within seconds. Modeling
      suggests that the device separates particles with a radial difference of 1
      nanometer.

PMID- 29599240
TI  - Chameleon-like elastomers with molecularly encoded strain-adaptive stiffening and
      coloration.
AB  - Active camouflage is widely recognized as a soft-tissue feature, and yet the
      ability to integrate adaptive coloration and tissuelike mechanical properties
      into synthetic materials remains elusive. We provide a solution to this problem
      by uniting these functions in moldable elastomers through the self-assembly of
      linear-bottlebrush-linear triblock copolymers. Microphase separation of the
      architecturally distinct blocks results in physically cross-linked networks that
      display vibrant color, extreme softness, and intense strain stiffening on par
      with that of skin tissue. Each of these functional properties is regulated by the
      structure of one macromolecule, without the need for chemical cross-linking or
      additives. These materials remain stable under conditions characteristic of
      internal bodily environments and under ambient conditions, neither swelling in
      bodily fluids nor drying when exposed to air.

PMID- 29599241
TI  - Self-heating-induced healing of lithium dendrites.
AB  - Lithium (Li) metal electrodes are not deployable in rechargeable batteries
      because electrochemical plating and stripping invariably leads to growth of
      dendrites that reduce coulombic efficiency and eventually short the battery. It
      is generally accepted that the dendrite problem is exacerbated at high current
      densities. Here, we report a regime for dendrite evolution in which the reverse
      is true. In our experiments, we found that when the plating and stripping current
      density is raised above ~9 milliamperes per square centimeter, there is
      substantial self-heating of the dendrites, which triggers extensive surface
      migration of Li. This surface diffusion heals the dendrites and smoothens the Li
      metal surface. We show that repeated doses of high-current-density healing
      treatment enables the safe cycling of Li-sulfur batteries with high coulombic
      efficiency.

PMID- 29599242
TI  - Shifts in disease dynamics in a tropical amphibian assemblage are not due to
      pathogen attenuation.
AB  - Infectious diseases rarely end in extinction. Yet the mechanisms that explain how
      epidemics subside are difficult to pinpoint. We investigated host-pathogen
      interactions after the emergence of a lethal fungal pathogen in a tropical
      amphibian assemblage. Some amphibian host species are recovering, but the
      pathogen is still present and is as pathogenic today as it was almost a decade
      ago. In addition, some species have defenses that are more effective now than
      they were before the epidemic. These results suggest that host recoveries are not
      caused by pathogen attenuation and may be due to shifts in host responses. Our
      findings provide insights into the mechanisms underlying disease transitions,
      which are increasingly important to understand in an era of emerging infectious
      diseases and unprecedented global pandemics.

PMID- 29599243
TI  - Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and
      malaria risk.
AB  - Malaria parasites invade red blood cells (RBCs), consume copious amounts of
      hemoglobin, and severely disrupt iron regulation in humans. Anemia often
      accompanies malaria disease; however, iron supplementation therapy inexplicably
      exacerbates malarial infections. Here we found that the iron exporter ferroportin
      (FPN) was highly abundant in RBCs, and iron supplementation suppressed its
      activity. Conditional deletion of the Fpn gene in erythroid cells resulted in
      accumulation of excess intracellular iron, cellular damage, hemolysis, and
      increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation,
      Q248H (glutamine to histidine at position 248), prevented hepcidin-induced
      degradation of FPN and protected against severe malaria disease. FPN Q248H
      appears to have been positively selected in African populations in response to
      the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress
      and malaria infection.

PMID- 29599244
TI  - Molecular mechanism of extreme mechanostability in a pathogen adhesin.
AB  - High resilience to mechanical stress is key when pathogens adhere to their target
      and initiate infection. Using atomic force microscopy-based single-molecule force
      spectroscopy, we explored the mechanical stability of the prototypical
      staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen
      beta. Steered molecular dynamics simulations revealed, and single-molecule force
      spectroscopy experiments confirmed, the mechanism by which this complex
      withstands forces of over 2 nanonewtons, a regime previously associated with the
      strength of a covalent bond. The target peptide, confined in a screwlike manner
      in the binding pocket of SdrG, distributes forces mainly toward the peptide
      backbone through an intricate hydrogen bond network. Thus, these adhesins can
      attach to their target with exceptionally resilient mechanostability, virtually
      independent of peptide side chains.

PMID- 29599245
TI  - Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor
      eIF2B.
AB  - The integrated stress response (ISR) is a conserved translational and
      transcriptional program affecting metabolism, memory, and immunity. The ISR is
      mediated by stress-induced phosphorylation of eukaryotic translation initiation
      factor 2alpha (eIF2alpha) that attenuates the guanine nucleotide exchange factor
      eIF2B. A chemical inhibitor of the ISR, ISRIB, reverses the attenuation of eIF2B
      by phosphorylated eIF2alpha, protecting mice from neurodegeneration and traumatic
      brain injury. We describe a 4.1-angstrom-resolution cryo-electron microscopy
      structure of human eIF2B with an ISRIB molecule bound at the interface between
      the beta and delta regulatory subunits. Mutagenesis of residues lining this
      pocket altered the hierarchical cellular response to ISRIB analogs in vivo and
      ISRIB binding in vitro. Our findings point to a site in eIF2B that can be
      exploited by ISRIB to regulate translation.

PMID- 29599248
TI  - Figuring out how I belong.

PMID- 29599246
TI  - Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven
      tumor immunity.
AB  - MICA and MICB are expressed by many human cancers as a result of cellular stress,
      and can tag cells for elimination by cytotoxic lymphocytes through natural killer
      group 2D (NKG2D) receptor activation. However, tumors evade this immune
      recognition pathway through proteolytic shedding of MICA and MICB proteins. We
      rationally designed antibodies targeting the MICA alpha3 domain, the site of
      proteolytic shedding, and found that these antibodies prevented loss of cell
      surface MICA and MICB by human cancer cells. These antibodies inhibited tumor
      growth in multiple fully immunocompetent mouse models and reduced human melanoma
      metastases in a humanized mouse model. Antitumor immunity was mediated mainly by
      natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This
      approach prevents the loss of important immunostimulatory ligands by human
      cancers and reactivates antitumor immunity.

PMID- 29599250
TI  - Treating those committed to your care.

PMID- 29599247
TI  - Destabilizing mutations encode nongenetic variation that drives evolutionary
      innovation.
AB  - Evolutionary innovations are often achieved by repurposing existing genes to
      perform new functions; however, the mechanisms enabling the transition from old
      to new remain controversial. We identified mutations in bacteriophage lambda's
      host-recognition gene J that confer enhanced adsorption to lambda's native
      receptor, LamB, and the ability to access a new receptor, OmpF. The mutations
      destabilize lambda particles and cause conformational bistability of J, which
      yields progeny of multiple phenotypic forms, each proficient at different
      receptors. This work provides an example of how nongenetic protein variation can
      catalyze an evolutionary innovation. We propose that cases where a single
      genotype can manifest as multiple phenotypes may be more common than previously
      expected and offer a general mechanism for evolutionary innovation.

PMID- 29599249
TI  - Acute retinal toxicity associated with a mixture of perfluorooctane and
      perfluorohexyloctane: failure of another indirect cytotoxicity analysis.
AB  - AIMS: To report new information related to acute retinal toxicity of Bio Octane
      Plus, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane.
      METHODS: This retrospective, descriptive case series reports the occurrence of
      acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus
      (batch number 1605148) was used as an endotamponade. Cytotoxicity
      biocompatibility tests and chemical analyses by Fourier-transformed infrared
      (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) of the
      presumed toxic product were performed. RESULTS: Four patients presented with
      acute severe visual loss after uneventful ocular surgery assisted by Bio Octane
      Plus (batch number 1605148) as endotamponade. Patients experienced extensive
      retinal vascular occlusion leading to retinal and optic nerve atrophy. The
      viability of ARPE-19 cells directly exposed to the suspect batch for 30 min was
      0%. The agarose overlay method used by the manufacturer according to European
      Union regulations and International Organization for Standardization (ISO)
      International Standards failed to detect toxicity. FTIR spectroscopy showed small
      differences between the non-toxic and toxic batches. GC-MS analysis showed the
      presence of bromotributyl stannane (whose toxicity was demonstrated in the dose
      response curve) only in the toxic batch of Bio Octane Plus. CONCLUSION: This is
      the third report of retinotoxicity due to PFO in 4 years. The clinical profiles
      may be missed as they resemble other postsurgical complications; therefore, more
      cases worldwide could have gone unreported. Protocols to determine cytotoxicity
      of intraocular medical devices and approved by the ISO International Standards
      based on indirect methods have failed and should be revised to ensure safety.

PMID- 29599251
TI  - RSPCA proposes two-tier farm subsidy system to support animal welfare.

PMID- 29599252
TI  - MPs call for action to safeguard science after Brexit.

PMID- 29599253
TI  - Grant aid for CCTV in Welsh abattoirs.

PMID- 29599255
TI  - Can IVF save the northern white rhino from extinction?
AB  - As the last male northern white rhino is euthanased, leaving just two females -
      his daughter and granddaughter - what is the future for this subspecies? Sophie
      Ingledew explains.

PMID- 29599257
TI  - Small animal disease surveillance: respiratory disease 2017.

PMID- 29599258
TI  - Brachycephalic obstructive airway syndrome.

PMID- 29599259
TI  - Practical guide to small animal theatre practice.

PMID- 29599262
TI  - Controlling TB versus wildlife conservation.

PMID- 29599263
TI  - RCVS and BVA are not to blame.

PMID- 29599264
TI  - Peter Stewart Hastie.
AB  - A veterinary surgeon who left a legacy of pursuing clinical excellence and never
      really retired.

PMID- 29599267
TI  - Maintain funding to cover GPs' indemnity costs, says BMA.

PMID- 29599269
TI  - Meet the First Authors.

PMID- 29599268
TI  - Temporal-Specific Interaction of NF-YC and CURLY LEAF during the Floral
      Transition Regulates Flowering.
AB  - The flowering time of higher plants is controlled by environmental cues and
      intrinsic signals. In Arabidopsis (Arabidopsis thaliana), flowering is
      accelerated by exposure to long-day conditions via the key photoperiod-induced
      factor FLOWERING LOCUS T (FT). Nuclear Factor-Y subunit C (NF-YC) proteins
      function as important mediators of epigenetic marks in different plant
      developmental stages and play an important role in the regulation of FT
      transcription, but the mechanistic details of this remain unknown. In this study,
      we show that Arabidopsis NF-YC homologs temporally interact with the histone
      methyltransferase CURLY LEAF (CLF) during the flowering transition. The binding
      of NF-YC antagonizes the association of CLF with chromatin and the CLF-dependent
      deposition of H3 lysine-27 trimethylation, thus relieving the repression of FT
      transcription and facilitating flowering under long-day conditions. Our findings
      reveal a novel mechanism of NF-YC/CLF-mediated epigenetic regulation of FT
      activation in photoperiod-induced flowering and, consequently, contribute to our
      understanding of how plants control developmental events in a temporal-specific
      regulatory manner.

PMID- 29599270
TI  - A Call to Make the Human Dimension of Science a Core Component of Scientific
      Journals.

PMID- 29599271
TI  - Complementing T Regulatory Cells to Combat Hypertension.

PMID- 29599272
TI  - Reprogramming the Endocardium: Trials and Tribulations.

PMID- 29599273
TI  - Cell-Based Therapy With Cardiosphere-Derived Cardiocytes: A New Hope for
      Pediatric Patients With Single Ventricle Congenital Heart Disease?

PMID- 29599274
TI  - My Life, My Heart, and My(osin) Binding Protein-C.

PMID- 29599275
TI  - Valentin Fuster: From Platelets to Preschoolers, Always With Scientific Rigor.

PMID- 29599276
TI  - Immune Modulation as a Treatment for Abdominal Aortic Aneurysms.

PMID- 29599277
TI  - Preclinical Studies of Stem Cell Therapy for Heart Disease.
AB  - As part of the TACTICS (Transnational Alliance for Regenerative Therapies in
      Cardiovascular Syndromes) series to enhance regenerative medicine, here, we
      discuss the role of preclinical studies designed to advance stem cell therapies
      for cardiovascular disease. The quality of this research has improved over the
      past 10 to 15 years and overall indicates that cell therapy promotes cardiac
      repair. However, many issues remain, including inability to provide complete
      cardiac recovery. Recent studies question the need for intact cells suggesting
      that harnessing what the cells release is the solution. Our contribution
      describes important breakthroughs and current directions in a cell-based approach
      to alleviating cardiovascular disease.

PMID- 29599278
TI  - Standards and Methodological Rigor in Pulmonary Arterial Hypertension Preclinical
      and Translational Research.
AB  - Despite advances in our understanding of the pathophysiology and the management
      of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for
      this devastating disease. Yet, few innovative therapies beyond the traditional
      pathways of endothelial dysfunction have reached clinical trial phases in PAH.
      Although there are inherent limitations of the currently available models of PAH,
      the leaky pipeline of innovative therapies relates, in part, to flawed
      preclinical research methodology, including lack of rigour in trial design,
      incomplete invasive hemodynamic assessment, and lack of careful translational
      studies that replicate randomized controlled trials in humans with attention to
      adverse effects and benefits. Rigorous methodology should include the use of
      prespecified eligibility criteria, sample sizes that permit valid statistical
      analysis, randomization, blinded assessment of standardized outcomes, and
      transparent reporting of results. Better design and implementation of preclinical
      studies can minimize inherent flaws in the models of PAH, reduce the risk of
      bias, and enhance external validity and our ability to distinguish truly
      promising therapies form many false-positive or overstated leads. Ideally,
      preclinical studies should use advanced imaging, study several preclinical
      pulmonary hypertension models, or correlate rodent and human findings and
      consider the fate of the right ventricle, which is the major determinant of
      prognosis in human PAH. Although these principles are widely endorsed, empirical
      evidence suggests that such rigor is often lacking in pulmonary hypertension
      preclinical research. The present article discusses the pitfalls in the design of
      preclinical pulmonary hypertension trials and discusses opportunities to create
      preclinical trials with improved predictive value in guiding early-phase drug
      development in patients with PAH, which will need support not only from
      researchers, peer reviewers, and editors but also from academic institutions,
      funding agencies, and animal ethics authorities.

PMID- 29599279
TI  - Letter by Lipshultz Regarding Article, "Anthracycline Cardiotoxicity: Worrisome
      Enough to Have You Quaking?"

PMID- 29599280
TI  - Response by Bernstein to Letter Regarding Article, "Anthracycline Cardiotoxicity:
      Worrisome Enough to Have You Quaking?"

PMID- 29599281
TI  - Correction to: Unspliced XBP1 Confers VSMC Homeostasis and Prevents Aortic
      Aneurysm Formation via FoxO4 Interaction.

PMID- 29599282
TI  - Seven days in medicine: 21-27 March 2018.

PMID- 29599283
TI  - A woman with a 10 year history of abdominal pain.

PMID- 29599284
TI  - Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral
      microbleeds in Chinese patients with atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are radiological markers
      which predict future intracerebral haemorrhage. Researchers are exploring how
      CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose
      of this study is to evaluate the correlation of non-vitamin K antagonist oral
      anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with
      AF. METHODS: We prospectively recruited Chinese patients with AF on NOAC therapy
      of >=30 days for 3T MRI brain for evaluation of CMBs and white matter
      hyperintensities. Patients with AF without prior exposure to oral anticoagulation
      were recruited as control group. RESULTS: A total of 282 patients were recruited,
      including 124 patients in NOAC group and 158 patients in control group. Mean
      duration of NOAC exposure was 723.8+/-500.3 days. CMBs were observed in 103
      (36.5%) patients. No significant correlation was observed between duration of
      NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie,
      age, hypertension, labile hypertension, stroke history and white matter scores),
      previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81
      to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white
      matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5),
      both exposure and duration of NOAC use were not predictive of presence of CMBs.
      CONCLUSIONS: In Chinese patients with AF, duration of NOAC exposure did not
      correlate with prevalence and burden of CMBs. Further studies with follow-up MRI
      are needed to determine if long-term NOAC therapy can lead to development of new
      CMBs.

PMID- 29599285
TI  - 2018 ACC/AHA Clinical Performance and Quality Measures for Cardiac
      Rehabilitation: A Report of the American College of Cardiology/American Heart
      Association Task Force on Performance Measures.

PMID- 29599286
TI  - Homologous recombination and the repair of DNA double-strand breaks.
AB  - Homologous recombination enables the cell to access and copy intact DNA sequence
      information in trans, particularly to repair DNA damage affecting both strands of
      the double helix. Here, we discuss the DNA transactions and enzymatic activities
      required for this elegantly orchestrated process in the context of the repair of
      DNA double-strand breaks in somatic cells. This includes homology search, DNA
      strand invasion, repair DNA synthesis, and restoration of intact chromosomes.
      Aspects of DNA topology affecting individual steps are highlighted. Overall,
      recombination is a dynamic pathway with multiple metastable and reversible
      intermediates designed to achieve DNA repair with high fidelity.

PMID- 29599287
TI  - The partial dissociation of MHC class I-bound peptides exposes their N terminus
      to trimming by endoplasmic reticulum aminopeptidase 1.
AB  - Endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 process N-terminally
      extended antigenic precursors for optimal loading onto major histocompatibility
      complex class I (MHC I) molecules. We and others have demonstrated that ERAP1
      processes peptides bound to MHC I, but the underlying mechanism is unknown. To
      this end, we utilized single-chain trimers (SCT) of the ovalbumin-derived epitope
      SIINFEKL (SL8) tethered to the H2-Kb MHC I determinant from mouse and introduced
      three substitutions, E63A, K66A, and W167A, at the A-pocket of the peptide
      binding groove in the MHC I heavy chain, which interact with the N termini of
      peptides. These variants significantly decreased SL8-presenting SCT at the cell
      surface in the presence of ERAP1, but did not affect overall SCT expression,
      indicating that ERAP1 trims the SL8 N terminus. Comparison of the X-ray crystal
      structures of WT and three variant SCTs revealed only minor perturbations of the
      peptide-binding domain in the variants. However, molecular dynamics simulations
      suggested that SL8 can dissociate partially within a sub-microsecond timescale,
      exposing its N terminus to the solvent. We also found that the C terminus of MHC
      I-bound SL8 remains deeply buried in the F-pocket of MHC I. Furthermore, free
      energy calculations revealed that the three SCT variants exhibit lower free
      energy barriers of N terminus dissociation than the WT Kb Taken together, our
      results are consistent with a previously observed model in which the partial
      dissociation of bound peptides from MHC I exposes their N terminus to trimming by
      ERAP1, whereas their C terminus is anchored at the F-pocket.

PMID- 29599288
TI  - Distinct domains in the matricellular protein Lonely heart are crucial for
      cardiac extracellular matrix formation and heart function in Drosophila.
AB  - The biomechanical properties of extracellular matrices (ECMs) are critical to
      many biological processes, including cell-cell communication and cell migration
      and function. The correct balance between stiffness and elasticity is essential
      to the function of numerous tissues, including blood vessels and the lymphatic
      system, and depends on ECM constituents (the "matrisome") and on their level of
      interconnection. However, despite its physiological relevance, the matrisome
      composition and organization remain poorly understood. Previously, we reported
      that the ADAMTS-like protein Lonely heart (Loh) is critical for recruiting the
      type IV collagen-like protein Pericardin to the cardiac ECM. Here, we utilized
      Drosophila as a simple and genetically amenable invertebrate model for studying
      Loh-mediated recruitment of tissue-specific ECM components such as Pericardin to
      the ECM. We focused on the functional relevance of distinct Loh domains to
      protein localization and Pericardin recruitment. Analysis of Loh deletion
      constructs revealed that one thrombospondin type 1 repeat (TSR1-1), which has an
      embedded WXXW motif, is critical for anchoring Loh to the ECM. Two other
      thrombospondin repeats, TSR1-2 and TSR1-4, the latter containing a CXXTCXXG
      motif, appeared to be dispensable for tethering Loh to the ECM but were crucial
      for proper interaction with and recruitment of Pericardin. Moreover, our results
      also suggested that Pericardin in the cardiac ECM primarily ensures the
      structural integrity of the heart, rather than increasing tissue flexibility. In
      conclusion, our work provides new insights into the roles of thrombospondin type
      1 repeats and advances our understanding of cardiac ECM assembly and function.

PMID- 29599289
TI  - Interaction between the AAA ATPase p97/VCP and a concealed UBX domain in the
      copper transporter ATP7A is associated with motor neuron degeneration.
AB  - The copper-transporting ATPase ATP7A contains eight transmembrane domains and is
      required for normal human copper homeostasis. Mutations in the ATP7A gene may
      lead to infantile-onset cerebral degeneration (Menkes disease); occipital horn
      syndrome (OHS), a related but much milder illness; or an adult-onset isolated
      distal motor neuropathy. The ATP7A missense mutation T994I is located in the
      sixth transmembrane domain of ATP7A, represents one of the variants associated
      with the latter phenotype, and is associated with an abnormal interaction with
      p97/valosin-containing protein (VCP), a hexameric AAA ATPase (ATPase associated
      with diverse cellular activities) with multiple biological functions. In this
      study, we further characterized this interaction and discovered a concealed UBX
      domain in the third lumenal loop of ATP7A, between its fifth and sixth
      transmembrane domains. We show that the T994I substitution results in
      conformational exposure of the UBX domain, which then binds the N-terminal domain
      of p97/VCP. We also show that this abnormal interaction occurs at or near the
      cell plasma membrane. The UBX domain has a conserved hydrophobic FP (Phe-Pro)
      motif, and substitution with di-alanine abrogated the interaction and restored
      the proper intracellular localization of ATP7A in the trans-Golgi network. Using
      protein MS, we identified potential coordinating components of the ATP7AT994I-p97
      complex, including NSFL1 cofactor (NSF1C or p47) that may be relevant to the
      pathophysiology and clinical effects associated with ATP7AT994I Our study
      represents the first report of p97/VCP binding to a UBX domain that is not
      normally exposed, resulting in an aberrant protein-protein interaction leading to
      motor neuron degeneration.

PMID- 29599290
TI  - TGFbeta and IGF1R signaling activates protein kinase A through differential
      regulation of ezrin phosphorylation in colon cancer cells.
AB  - Aberrant cell survival plays a critical role in cancer progression and
      metastasis. We have previously shown that ezrin, a cAMP-dependent protein kinase
      A-anchoring protein (AKAP), is up-regulated in colorectal cancer (CRC) liver
      metastasis. Phosphorylation of ezrin at Thr-567 activates ezrin and plays an
      important role in CRC cell survival associated with XIAP and survivin up
      regulation. In this study, we demonstrate that in FET and GEO colon cancer cells,
      knockdown of ezrin expression or inhibition of ezrin phosphorylation at Thr-567
      increases apoptosis through protein kinase A (PKA) activation in a cAMP
      independent manner. Transforming growth factor (TGF) beta signaling inhibits
      ezrin phosphorylation in a Smad3-dependent and Smad2-independent manner and
      regulates pro-apoptotic function through ezrin-mediated PKA activation. On the
      other hand, ezrin phosphorylation at Thr-567 by insulin-like growth factor 1
      receptor (IGF1R) signaling leads to cAMP-dependent PKA activation and enhances
      cell survival. Further studies indicate that phosphorylated ezrin forms a complex
      with PKA RII, and dephosphorylated ezrin dissociates from the complex and
      facilitates the association of PKA RII with AKAP149, both of which activate PKA
      yet lead to either cell survival or apoptosis. Thus, our studies reveal a novel
      mechanism of differential PKA activation mediated by TGFbeta and IGF1R signaling
      through regulation of ezrin phosphorylation in CRC, resulting in different cell
      fates. This is of significance because TGFbeta and IGF1R signaling pathways are
      well-characterized tumor suppressor and oncogenic pathways, respectively, with
      important roles in CRC tumorigenesis and metastasis. Our studies indicate that
      they cross-talk and antagonize each other's function through regulation of ezrin
      activation. Therefore, ezrin may be a potential therapeutic target in CRC.

PMID- 29599291
TI  - TREM2-activating antibodies abrogate the negative pleiotropic effects of the
      Alzheimer's disease variant Trem2R47H on murine myeloid cell function.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) is an orphan immune
      receptor expressed on cells of myeloid lineage such as macrophages and microglia.
      The rare variant R47H TREM2 is associated with an increased risk for Alzheimer's
      disease, supporting the hypothesis that TREM2 loss of function may exacerbate
      disease progression. However, a complete knockout of the TREM2 gene in different
      genetic models of neurodegenerative diseases has been reported to result in both
      protective and deleterious effects on disease-related end points and myeloid cell
      function. Here, we describe a Trem2R47H transgenic mouse model and report that
      even in the absence of additional genetic perturbations, this variant clearly
      confers a loss of function on myeloid cells. The Trem2R47H variant-containing
      myeloid cells exhibited subtle defects in survival and migration and displayed an
      unexpected dysregulation of cytokine responses in a lipopolysaccharide challenge
      environment. These subtle phenotypic defects with a gradation in severity across
      genotypes were confirmed in whole-genome RNA-Seq analyses of WT, Trem2-/-, and
      Trem2R47H myeloid cells under challenge conditions. Of note, TREM2-activating
      antibodies that boost proximal signaling abrogated survival defects conferred by
      the variant and also modulated migration and cytokine responses in an antibody-,
      ligand-, and challenge-dependent manner. In some instances, these antibodies also
      boosted WT myeloid cell function. Our studies provide a first glimpse into the
      boost in myeloid cell function that can be achieved by pharmacological modulation
      of TREM2 activity that can potentially be ameliorative in neurodegenerative
      diseases such as Alzheimer's disease.

PMID- 29599292
TI  - Mitochondrial oxidative stress causes insulin resistance without disrupting
      oxidative phosphorylation.
AB  - Mitochondrial oxidative stress, mitochondrial dysfunction, or both have been
      implicated in insulin resistance. However, disentangling the individual roles of
      these processes in insulin resistance has been difficult because they often occur
      in tandem, and tools that selectively increase oxidant production without
      impairing mitochondrial respiration have been lacking. Using the dimer/monomer
      status of peroxiredoxin isoforms as an indicator of compartmental hydrogen
      peroxide burden, we provide evidence that oxidative stress is localized to
      mitochondria in insulin-resistant 3T3-L1 adipocytes and adipose tissue from mice.
      To dissociate oxidative stress from impaired oxidative phosphorylation and study
      whether mitochondrial oxidative stress per se can cause insulin resistance, we
      used mitochondria-targeted paraquat (MitoPQ) to generate superoxide within
      mitochondria without directly disrupting the respiratory chain. At <=10 MUm,
      MitoPQ specifically increased mitochondrial superoxide and hydrogen peroxide
      without altering mitochondrial respiration in intact cells. Under these
      conditions, MitoPQ impaired insulin-stimulated glucose uptake and glucose
      transporter 4 (GLUT4) translocation to the plasma membrane in both adipocytes and
      myotubes. MitoPQ recapitulated many features of insulin resistance found in other
      experimental models, including increased oxidants in mitochondria but not
      cytosol; a more profound effect on glucose transport than on other insulin
      regulated processes, such as protein synthesis and lipolysis; an absence of overt
      defects in insulin signaling; and defective insulin- but not AMP-activated
      protein kinase (AMPK)-regulated GLUT4 translocation. We conclude that elevated
      mitochondrial oxidants rapidly impair insulin-regulated GLUT4 translocation and
      significantly contribute to insulin resistance and that MitoPQ is an ideal tool
      for studying the link between mitochondrial oxidative stress and regulated GLUT4
      trafficking.

PMID- 29599293
TI  - TagF-mediated repression of bacterial type VI secretion systems involves a direct
      interaction with the cytoplasmic protein Fha.
AB  - The bacterial type VI secretion system (T6SS) delivers effectors into eukaryotic
      host cells or toxins into bacterial competitor for survival and fitness. The T6SS
      is positively regulated by the threonine phosphorylation pathway (TPP) and
      negatively by the T6SS-accessory protein TagF. Here, we studied the mechanisms
      underlying TagF-mediated T6SS repression in two distinct bacterial pathogens,
      Agrobacterium tumefaciens and Pseudomonas aeruginosa. We found that in A.
      tumefaciens, T6SS toxin secretion and T6SS-dependent antibacterial activity are
      suppressed by a two-domain chimeric protein consisting of TagF and PppA, a
      putative phosphatase. Remarkably, this TagF domain is sufficient to post
      translationally repress the T6SS, and this inhibition is independent of TPP. This
      repression requires interaction with a cytoplasmic protein, Fha, critical for
      activating T6SS assembly. In P. aeruginosa, PppA and TagF are two distinct
      proteins that repress T6SS in TPP-dependent and -independent pathways,
      respectively. P. aeruginosa TagF interacts with Fha1, suggesting that formation
      of this complex represents a conserved TagF-mediated regulatory mechanism. Using
      TagF variants with substitutions of conserved amino acid residues at predicted
      protein-protein interaction interfaces, we uncovered evidence that the TagF-Fha
      interaction is critical for TagF-mediated T6SS repression in both bacteria. TagF
      inhibits T6SS without affecting T6SS protein abundance in A. tumefaciens, but
      TagF overexpression reduces the protein levels of all analyzed T6SS components in
      P. aeruginosa Our results indicate that TagF interacts with Fha, which in turn
      could impact different stages of T6SS assembly in different bacteria, possibly
      reflecting an evolutionary divergence in T6SS control.

PMID- 29599295
TI  - Diabetes Distress and Glycemic Control: The Buffering Effect of Autonomy Support
      From Important Family Members and Friends.
AB  - OBJECTIVE: To examine whether autonomy support (defined as social support for an
      individual's personal agency) for diabetes management from informal health
      supporters (family/friends) reduces the detrimental effects of diabetes distress
      on glycemic control. RESEARCH DESIGN AND METHODS: Three hundred eight veterans
      with type 2 diabetes and one or more risk factors for diabetes complications
      completed a survey that included measures of diabetes distress and perceived
      autonomy support from their main informal health supporter. Hemoglobin A1c
      (HbA1c) data from 12 months before and after the survey were extracted from
      electronic medical records. Linear mixed modeling examined the main effects and
      interaction of autonomy support and diabetes distress on repeated measures of
      HbA1c over the 12 months after the survey, controlling for mean prior 12-month
      HbA1c, time, insulin use, age, and race/ethnicity. RESULTS: Diabetes distress (B
      = 0.12 [SE 0.05]; P = 0.023) was associated with higher and autonomy support (B =
      -0.16 [SE 0.07]; P = 0.032) with lower subsequent HbA1c levels. Autonomy support
      moderated the relationship between diabetes distress and HbA1c (B = -0.13 [SE
      0.06]; P = 0.027). Greater diabetes distress was associated with higher HbA1c at
      low (B = 0.21 [SE 07]; P = 0.002) but not high (B = 0.01 [SE 0.07]; P = 0.890)
      levels of autonomy support. CONCLUSIONS: Autonomy support from main health
      supporters may contribute to better glycemic control by ameliorating the effects
      of diabetes distress. Interventions that reduce diabetes distress and enhance the
      autonomy supportiveness of informal supporters may be effective approaches to
      improving glycemic control.

PMID- 29599294
TI  - Munc18-2, but not Munc18-1 or Munc18-3, controls compound and single-vesicle
      regulated exocytosis in mast cells.
AB  - Mast cells (MCs) play pivotal roles in many inflammatory conditions including
      infections, anaphylaxis, and asthma. MCs store immunoregulatory compounds in
      their large cytoplasmic granules and, upon stimulation, secrete them via
      regulated exocytosis. Exocytosis in many cells requires the participation of
      Munc18 proteins (also known as syntaxin-binding proteins), and we found that
      mature MCs express all three mammalian isoforms: Munc18-1, -2, and -3. To study
      their functions in MC effector responses and test the role of MC degranulation in
      anaphylaxis, we used conditional knockout (cKO) mice in which each Munc18 protein
      was deleted exclusively in MCs. Using recordings of plasma membrane capacitance
      for high-resolution analysis of exocytosis in individual MCs, we observed an
      almost complete absence of exocytosis in Munc18-2-deficient MCs but intact
      exocytosis in MCs lacking Munc18-1 or Munc18-3. Stereological analysis of EM
      images of stimulated MCs revealed that the deletion of Munc18-2 also abolishes
      the homotypic membrane fusion required for compound exocytosis. We confirmed the
      severe defect in regulated exocytosis in the absence of Munc18-2 by measuring the
      secretion of mediators stored in MC granules. Munc18-2 cKO mice had normal
      morphology, development, and distribution of their MCs, indicating that Munc18-2
      is not essential for the migration, retention, and maturation of MC-committed
      progenitors. Despite that, we found that Munc18-2 cKO mice were significantly
      protected from anaphylaxis. In conclusion, MC-regulated exocytosis is required
      for the anaphylactic response, and Munc18-2 is the sole Munc18 isoform that
      mediates membrane fusion during MC degranulation.

PMID- 29599297
TI  - Immediate effects of an artificial change in hoof angulation on the dorsal
      metacarpophalangeal joint angle and cross-sectional areas of both flexor tendons.
AB  - Corrective shoeing is used to change hoof angulation with the intention to
      influence the angulation of the digital joints to reduce strain on associated
      tendons. The objective of this study is to examine how gradual changes in hoof
      angulation affect the dorsal metacarpophalangeal joint (DMPJ) angulation and
      cross-sectional areas (CSAs) of the deep digital flexor tendon (DDFT) and
      superficial digital flexor tendon (SDFT) concerning the individual toe
      conformation. Forelimbs of 30 horses were examined barefoot and equipped with 5
      degrees , 10 degrees  and 20 degrees  toe wedges (TWs) and heel wedges (HWs).
      Phalangeal angulation and lengths were measured in lateromedial radiographs of
      the digit. CSAs of both flexor tendons was calculated in sonographic images.
      Significant effects on the DMPJ and CSA of the DDFT/SDFT were measured with 10
      degrees  and 20 degrees  HWs or 20 degrees  TWs. Both flexor tendons showed
      increasing CSA after heel elevation. Significant interindividual variations
      occurred. Phalangeal angulation and length influenced the responsivity of the
      parameters to a changed hoof angulation. Significant impact of corrective shoeing
      on the DMPJ and flexor tendons is related to a distinct change in hoof
      orientation and varies with individual toe conformation. Similar response of the
      DDFT and SDFT to raised and lowered hoof orientation needs further investigation
      for a more specific application of therapeutic shoeing.

PMID- 29599296
TI  - Relationship Between Metabolic Syndrome, Alanine Aminotransferase Levels, and
      Liver Disease Severity in a Multiethnic North American Cohort With Chronic
      Hepatitis B.
AB  - OBJECTIVE: Metabolic syndrome (MS) is prevalent and is associated with adverse
      outcomes of liver disease. We evaluated the prevalence of MS and its influence on
      alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate
      aminotransferase-to-platelet ratio index (APRI), in a large, multiethnic North
      American cohort with chronic hepatitis B (HBV) infection. RESEARCH DESIGN AND
      METHODS: Adults with chronic HBV from 21 centers within the U.S. and Canada were
      evaluated at baseline and for up to 5 years (median 3.7 years) of follow-up. MS
      was defined as the presence of at least three of five criteria including waist
      circumference, blood pressure, glucose, triglyceride, and HDL levels. RESULTS:
      Analysis included 777 participants, of whom 171 (22%) had MS. Participants with
      MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more often
      male (61% vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago
      (60% vs. 43%). MS was not associated with ALT or APRI at baseline. Upon adjusted
      multivariable analysis of serial ALT values, ALT was significantly higher (mean
      12%; P = 0.02) among those with MS at baseline and even higher (mean 19%; P =
      0.003) among those with persistent MS compared with those with persistent absence
      of MS. MS was not associated with serial APRI on follow-up. CONCLUSIONS: MS was
      prevalent in this HBV cohort and was independently associated with higher ALT
      levels longitudinally. These findings highlight the importance of screening for
      MS and the potential for MS to influence ALT and its interpretation in the
      context of HBV treatment decisions.

PMID- 29599298
TI  - Autogenous vaccination reduces antimicrobial usage and mortality rates in a herd
      facing severe exudative epidermitis outbreaks in weaned pigs.
AB  - This study was conducted in a commercial 1000-sow herd facing recurrent exudative
      epidermitis (EE) outbreaks during the nursery period and assessed the efficacy of
      autogenous vaccination in controlling such outbreaks. The vaccine was produced
      using three Staphylococcus hyicus isolates recovered from affected pigs shortly
      before the onset of the study. All of those isolates were positive for the exhB
      gene, which encodes the exfoliative toxin type B (ExhB). From four consecutive
      farrowing batches of sows, two batches were vaccinated (V) against S hyicus at
      five and two weeks before farrowing, and two sow batches remained non-vaccinated
      (NV). Vaccination efficacy was primarily determined by the levels of
      metaphylactic antimicrobial usage, and the morbidity and mortality data for the
      pigs of the V and NV sows. The total amount of antimicrobials used
      metaphylactically against EE in pigs among the V and NV farrowing batches was
      39,600 and 88,550 mg, respectively. The used daily dose pig to animal daily dose
      pig ratio for the V and NV batches were 1.31 and 1.79, respectively (a ratio of
      0.8 to 1.2 is indicative of correct dosing). The morbidity and mortality rates
      were V=6.50 and NV=14.36 (P=0.008), and V=2.59 and NV=5.02 (P=0.000),
      respectively. To conclude, autogenous vaccination of the sows with a vaccine
      based on exhB-positive S hyicus isolates reduced metaphylactic treatment with
      antimicrobials as well as the morbidity and mortality rates in weaned pigs
      compared with pigs from NV sow batches.

PMID- 29599299
TI  - Identification of Patients Expected to Benefit from Electronic Alerts for Acute
      Kidney Injury.
AB  - BACKGROUND AND OBJECTIVES: Electronic alerts for heterogenous conditions such as
      AKI may not provide benefit for all eligible patients and can lead to alert
      fatigue, suggesting that personalized alert targeting may be useful. Uplift-based
      alert targeting may be superior to purely prognostic-targeting of interventions
      because uplift models assess marginal treatment effect rather than likelihood of
      outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a secondary
      analysis of a clinical trial of 2278 adult patients with AKI randomized to an
      automated, electronic alert system versus usual care. We used three uplift
      algorithms and one purely prognostic algorithm, trained in 70% of the data, and
      evaluated the effect of targeting alerts to patients with higher scores in the
      held-out 30% of the data. The performance of the targeting strategy was assessed
      as the interaction between the model prediction of likelihood to benefit from
      alerts and randomization status. The outcome of interest was maximum relative
      change in creatinine from the time of randomization to 3 days after
      randomization. RESULTS: The three uplift score algorithms all gave rise to a
      significant interaction term, suggesting that a strategy of targeting individuals
      with higher uplift scores would lead to a beneficial effect of AKI alerting, in
      contrast to the null effect seen in the overall study. The prognostic model did
      not successfully stratify patients with regards to benefit of the intervention.
      Among individuals in the high uplift group, alerting was associated with a median
      reduction in change in creatinine of -5.3% (P=0.03). In the low uplift group,
      alerting was associated with a median increase in change in creatinine of +5.3%
      (P=0.005). Older individuals, women, and those with a lower randomization
      creatinine were more likely to receive high uplift scores, suggesting that alerts
      may benefit those with more slowly developing AKI. CONCLUSIONS: Uplift modeling,
      which accounts for treatment effect, can successfully target electronic alerts
      for AKI to those most likely to benefit, whereas purely prognostic targeting
      cannot.

PMID- 29599300
TI  - Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis Patients:
      A Prospective Cohort Study.
AB  - BACKGROUND AND OBJECTIVES: Deficiency of essential trace elements and excess of
      potentially toxic trace elements are common in patients on hemodialysis. Whether
      these abnormalities are associated with poor outcomes is unknown but worth
      investigating, because they are potentially treatable. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We did a prospective longitudinal study of 1278
      patients on incident hemodialysis, assessing blood concentrations of 25 trace
      elements at baseline. We used adjusted logistic regression to evaluate the
      association between trace element status and four outcomes (death, cardiovascular
      events, systemic infection, and hospitalization). A priori hypotheses concerned
      (1) deficiency of zinc, selenium, and manganese and (2) excess of lead, arsenic,
      and mercury. Concentrations of the other 19 elements were tested in hypothesis
      generating analyses. RESULTS: Over 2 years of follow-up, 260 (20%) patients died,
      285 (24%) experienced a cardiovascular event, 117 (10%) were hospitalized for
      systemic infection, and 928 (77%) were hospitalized for any cause. Lower
      concentrations of zinc or manganese and higher concentrations of lead, arsenic,
      or mercury were not independently associated with higher risk of clinical
      outcomes. Lower concentrations of selenium were strongly and independently
      associated with death (odds ratio, 0.86 per decile; 99.2% confidence interval,
      0.80 to 0.93) and all-cause hospitalization (odds ratio, 0.92 per decile; 99.2%
      confidence interval, 0.86 to 0.98). In exploratory analyses, higher copper
      concentrations were significantly associated with higher risk of death (odds
      ratio, 1.07 per decile; 99.2% confidence interval, 1.00 to 1.15), and cadmium
      levels in the highest decile were associated with higher risk of death (odds
      ratio, 1.89; 99.2% confidence interval, 1.06 to 3.38). CONCLUSIONS: Lower levels
      of zinc or manganese and higher concentrations of lead, arsenic, or mercury were
      not associated with higher risk of clinical outcomes, but lower concentrations of
      selenium were strongly and independently associated with the risks of death and
      hospitalization.

PMID- 29599301
TI  - Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse
      Models of Cancer.
AB  - The tumor microenvironment (TME) contains stromal cells in a complex interaction
      with cancer cells. This relationship has become better understood with the use of
      fluorescent proteins for in vivo imaging, originally developed by our
      laboratories. Spectrally-distinct fluorescent proteins can used for color-coded
      imaging of the complex interaction of the tumor microenvironment in the living
      state using cancer cells expressing a fluorescent protein of one color and host
      mice expressing another-color fluorescent protein. Cancer cells engineered in
      vitro to express a fluorescent protein were orthotopically implanted into
      transgenic mice expressing a fluorescent protein of a different color. Confocal
      microscopy was then used for color-coded imaging of the TME. Color-coded imaging
      of the TME has enabled us to discover that stromal cells are necessary for
      metastasis. Patient-derived orthotopic xenograft (PDOX) tumors were labeled by
      first passaging them orthotopically through transgenic nude mice expressing
      either green, red, or cyan fluorescent protein in order to label the stromal
      cells of the tumor. The colored stromal cells become stably associated with the
      PDOX tumors through multiple passages in transgenic colored mice or non-colored
      mice. The fluorescent protein-expressing stromal cells included cancer-associated
      fibroblasts and tumor-associated macrophages. The cancer cells in PDOX models can
      also be labeled with a telomerase-dependent adenovirus containing the gene for
      green fluorescent protein. Using this model, specific cancer-cell or stromal-cell
      targeting by potential therapeutics can be visualized. Color-coded imaging
      enabled the visualization of apparent fusion of cancer and stromal cells. Color
      coded imaging is a powerful tool visualizing the interaction of cancer and
      stromal cells during cancer progression and treatment.

PMID- 29599302
TI  - Molecular Sequence of Events and Signaling Pathways in Cerebral Metastases.
AB  - Brain metastases are the leading cause of morbidity and mortality among cancer
      patients, and are reported to occur in about 40% of cancer patients with
      metastatic disease in the United States of America. Primary tumor cells appear to
      detach from the parent tumor site, migrate, survive and pass through the blood
      brain barrier in order to establish cerebral metastases. This complex process
      involves distinct molecular and genetic mechanisms that mediate metastasis from
      these primary organs to the brain. Furthermore, an interaction between the
      invading cells and cerebral milieu is shown to promote this process as well.
      Here, we review the mechanisms by which primary cancer cells metastasize to the
      brain via a mechanism called epithelial-to-mesenchymal transition, as well as the
      involvement of certain microRNA and genetic aberrations implicated in cerebral
      metastases from the lung, breast, skin, kidney and colon. While the mechanisms
      governing the development of brain metastases remain a major hindrance in
      treatment, understanding and identification of the aforementioned molecular
      pathways may allow for improved management and discovery of novel therapeutic
      targets.

PMID- 29599303
TI  - Radiotherapy May Offer a Recurrence and Survival Benefit in Rectal Cancers
      Treated Surgically with Transanal Endoscopic Microsurgery: A Systematic Review
      and Meta-analysis.
AB  - BACKGROUND/AIM: Several studies report outcomes of Transanal Endoscopic
      Microsurgery (TEMS) surgery in combination with radiotherapy, however the
      combination of those treatments is provided mostly on an adhoc individual basis
      and the role of radiotherapy remains unclear. The aim of this study was to
      identify the effect of neo-adjuvant or adjuvant radiotherapy in the oncological
      outcomes of rectal cancer treated surgically with TEMS. MATERIALS AND METHODS: We
      performed a systematic review of the literature on MEDLINE and Pubmed databases.
      Data were extracted by two independent reviewers and meta-analyzed using an
      inverse variance heterogeneity model to calculate overall (pooled) effect sizes
      for survival or recurrence of disease against neo+/-adjuvant treatment. RESULTS:
      A total of 48 studies were included in the qualitative meta-analysis which
      included 3,285 patients with rectal cancer. The overall survival odds ratio (OR),
      was 9.39 (95% CI=6.1-14.4) with a Cochran's Q variable of 151.7 on 47 degrees of
      freedom (d.f.) (p=0.000). Recurrence-free OR was 8.7 (95%CI=6.58-11.44) with a
      Cochran's Q variable of Q=145.2 on 44 d.f. (p=0.000). Studies which contained
      more than 10% of pT3 tumours, and provided neo+/-adjuvant treatment in more than
      35% of cases, were associated with survival benefit, as demonstrated by an
      overall odds of survival of 32.2 (95%CI=16.3-63.5, p=0.001, Q=8.4, p=0.21).
      Studies that contained more than 10% of pT3 tumours and provided neo+/-adjuvant
      treatment in more than 20% of the cases had an overall effect size of recurrence
      free odds of 20.23 (95%CI=13.84-29.57, p=0.000, Q=2.18, p=0.54). CONCLUSION:
      There seems to be a benefit from radiotherapy on overall survival and recurrence
      free odds, which is more apparent in cohorts with more than 10% of pT3 tumours.
      Our results suggest that neo-adjuvant or adjuvant radiotherapy should be
      considered for inclusion in formal treatment protocols for rectal cancers treated
      with TEMS as they offer a recurrence and survival benefit.

PMID- 29599304
TI  - Aspirin in the Management of Patients with Prostate Cancer Undergoing
      Radiotherapy: Friend or Foe?
AB  - Aspirin has cyclooxygenase-2 (COX2)-mediated anti-inflammatory and anti-coagulant
      properties that may confer a positive effect in preventing and limiting the
      progression of prostate cancer. Prostate cancer has been shown to have poor
      treatment outcomes due to therapeutic resistance; therefore, COX2 inhibition
      caused by aspirin could represent an opportunity to augment current therapies.
      This is particularly of interest to patients undergoing radiation therapy (RT)
      where inflammation is a common side-effect. This review discusses the evidence
      for the potential role of aspirin in the management of patients with prostate
      cancer undergoing RT.

PMID- 29599305
TI  - Clinicopathological and Molecular Factors, Risk Factors, Treatment Outcomes and
      Risk of Recurrence in Mesenteric and Retroperitoneal Extragastrointestinal
      Stromal Tumors.
AB  - BACKGROUND/AIM: The objective of the present study was to determine the
      clinicopathological factors and treatment outcomes of patients suffering from
      mesenteric or retroperitoneal extragastrointestinal stromal tumors (EGISTs).
      MATERIALS AND METHODS: A detailed search in PubMed, using the key words
      "extragastrointestinal stromal tumors" and "EGIST", found eight studies
      fulfilling the criteria of this study. RESULTS: Thirty-six patients with a
      mesenteric and 24 patients with a retroperitoneal EGIST were analyzed, with a
      follow-up period ranging from 2 to 192 months. Retroperitoneal tumors presented
      as larger tumors than mesenteric ones, with 95% and 93% immunohistochemical
      positivity for CD117 antigen, respectively. Surgical resection was performed in
      91% of cases, with 57% of patients with mesenteric and 70% of patients with
      retroperitoneal EGISTs being alive at the last follow-up. CONCLUSION: EGISTs most
      commonly are of considerable size and usually with a high mitotic count,
      rendering them high-risk tumors. Tumor necrosis, nuclear atypia, tumor histology,
      and mutations in the tyrosine kinase KIT or platelet-derived growth factor
      receptor A (PDGFRA) gene, seem to influence tumor behavior.

PMID- 29599306
TI  - Laparoscopic Intragastric Surgery for Treating Early Gastric Cancer.
AB  - BACKGROUND/AIM: Although there is an increasing number of studies on laparoscopic
      resection of early gastric cancer (EGC), as of 2018 no standardized strategy
      exists. We reviewed available literature dealing with laparoscopic intragastric
      (intraluminal) surgery (LIGS) conducted for patients with EGC to better define
      indications, benefits and limitations of this particular minimally invasive
      technique. MATERIALS AND METHODS: PubMed, MEDLINE, Science Direct, Scopus, Web of
      Science, Google Scholar and ResearchGate were the search engines investigated.
      Only LIGS for EGC was entertained; studies conducted for other gastric diseases
      were excluded. Suitable articles written in all languages were included in the
      review. RESULTS: As of 2018, we found 19 studies dealing with LIGS for EGC:
      studies on 72 humans and four pigs were identified. Among 72 human participants,
      there were 59 mucosal, five submucosal and one subserosal cancer. CONCLUSION:
      Based on our review, LIGS appears as a cogent option to endoscopic resection for
      treating superficial EGC.

PMID- 29599307
TI  - Ethanolic Extract of Traditional Chinese Medicine (TCM) Gamboge Inhibits Colon
      Cancer via the Wnt/Beta-Catenin Signaling Pathway in an Orthotopic Mouse Model.
AB  - BACKGROUND/AIM: The aim of the present study was to investigate the efficacy of
      an ethanolic extract of gamboge (EEG), a traditional Chinese medicine (TCM), both
      in vitro on colon cancer cells and in vivo in an orthotopic mouse model of human
      colon cancer. MATERIALS AND METHODS: The in vitro cytotoxicity of EEG on colon
      cancer cells was determined with the CCK8 proliferation assay and the Annexin V
      PE/7-AAD apoptosis assay. Efficacy of EEG in vivo was evaluated in an orthotopic
      mouse model of human colon cancer implated with the green fluorescent protein
      expressing human colon cancer cell line SW480-GFP. The tumor-bearing mice were
      treated with vehicle (0.2 ml/dose normal saline, po, daily), irinotecan (50
      mg/kg/dose, ip, twice a week), 5-FU (15 mg/kg/dose, ip, every other day) as
      positive controls or EEG at doses of 12.5, 25 and 50 mg/kg/dose, po, daily. Real
      time fluorescence imaging was performed to determine tumor inhibition in each
      treated group compared to the untreated controls. The protein expression of beta
      catenin, MMP-7, cyclin D1 and E-cadherin in the tumors was analyzed by
      immunohistochemistry. RESULTS: EEG significantly induced proliferation inhibition
      and apoptosis of SW480 colon cancer cells in vitro in a dose-dependent manner.
      Tumor growth in the colon-cancer orthotopic model was significantly inhibited by
      irinotecan, 5-FU and all three doses of EEG. The efficacy of EEG was comparable
      to irinotecan and 5-FU. Irinotecan, 5-FU and 50 mg/kg EEG significantly decreased
      the protein expression of beta-catenin and MMP-7. Cyclin D1 expression was
      decreased and E-cadherin expression was increased by irinotecan, 5-FU and all
      three doses of EEG. CONCLUSION: The present study demonstrates anti-tumor
      efficacy of EEG on colon cancer both in vitro and in vivo through inducing
      proliferation inhibition and apoptosis of SW480 colon cancer cells and inhibiting
      tumor growth, respectively. EEG exerts anti-tumor activity at least partly via
      down-regulation of the Wnt/beta-catenin signaling pathway.

PMID- 29599308
TI  - Differential Organ-targeting and Cellular Characteristics of Metastatic Human
      Pancreatic Cancer Cell Lines in Mouse Models.
AB  - BACKGROUND/AIM: The lethal characteristic of pancreatic cancer is metastasis
      which is recalcitrant to currently-used chemotherapy. Our aim was to understand
      metastasis at the cellular level. We previously reported that multi-nucleate
      cells or spindle cells were more prominent in pancreatic cancer metastasis than
      in the primary tumor. In the present report, we investigated four representative
      human pancreatic cell lines for differences in cell morphology between the
      primary tumor and various metastatic organ targets for each cell line. MATERIALS
      AND METHODS: Human pancreatic cancer cell lines AsPC-1, Panc-1, KP2 and KP3 were
      used. Pancreatic cancer cells were injected into spleen of nude mice resulting in
      experimental metastasis to various organs which were observed at the cellular
      level when the organs were placed into culture. RESULTS: AsPC-1 and KP2
      pancreatic cells formed many experimental liver metastases, in contrast to Panc-1
      and KP3. Lung metastasis was only observed for AsPC-1. In the cultures
      established from the primary and metastatic tumors, multi-nucleate cells were
      found to be more prominent in the metastasis of the pancreatic cell lines with
      frequent metastasis, AsPC-1 and KP2. Spindle-like cells were observed prominently
      in AsPC-1 lung metastasis. CONCLUSION: Human pancreatic cancer cell lines have
      differential metastatic characteristics with regard to target organs and cell
      morphology changes. Multi-nucleate and spindle cells may play an important role
      in pancreatic cancer metastasis to the liver and lung, respectively.

PMID- 29599309
TI  - MEKK3 Sustains EMT and Stemness in Pancreatic Cancer by Regulating YAP and TAZ
      Transcriptional Activity.
AB  - BACKGROUND/AIM: Pancreatic cancer is one of the most threatening and poorly
      understood human malignancies. MEKK3 (MAP3K3) is a serine/threonine kinase
      activated by different signaling pathways. YAP and TAZ are critical oncogenic
      effectors in pancreatic cancer. We hypothesized that MEKK3 could sustain
      pancreatic cancer by inducing YAP/TAZ oncogenic activities. MATERIALS AND
      METHODS: In Panc1 and AsPC1 pancreatic cancer cell lines MEKK3 was knocked-out
      (KO) by the CRISPR/Cas9 method. These cells were used to evaluate MEKK3
      contribution to the expression of YAP/TAZ and their target genes, cell migration,
      stemness, and in vivo tumor growth. RESULTS: MEKK3 KO reduced both EMT and cell
      migration, the size of 3D colonies and the percentage of CD44+/CD24+/EpCAM+ CSC,
      promoter recruitment of YAP/TAZ and the expression of their target genes. It
      reduced tumor growth and prolonged mice overall survival. CONCLUSION: Silencing
      of MEKK3 represents a valid approach to revert in vivo the aggressiveness of
      pancreatic cancer by modulating YAP/TAZ transcriptional activities.

PMID- 29599310
TI  - Antitumor Activity of Novel Bone-seeking, alpha-emitting 224Ra-solution in a
      Breast Cancer Skeletal Metastases Model.
AB  - BACKGROUND/AIM: Bone metastases are associated with increased morbidity and poor
      prognosis in a variety of cancers. The present study investigated the effects of
      targeted radionuclide therapy with alpha-emitting, bone-seeking radium-224
      (224Ra) on osteolytic bone metastasis of MDA-MB-231(SA)-GFP human breast cancer
      cells injected intracardially into nude mice. MATERIALS AND METHODS: Vehicle,
      ethylenediamine tetra (methylene phosphonic acid) (EDTMP) and 224Ra-solution (45,
      91 or 179 kBq/kg) with EDTMP were intravenously administered to mice two days
      after cell injection. The bone-seeking EDTMP was added to the 224Ra-solution to
      improve bone targeting of 212Pb, which is a progeny of 224Ra. RESULTS: Radium-224
      solution treatment decreased in a dose-dependent manner the areas of osteolytic
      lesions in the hind limbs and the number of tumor foci in the whole skeleton, and
      extended survival. Paraplegia was not observed in 179 kBq/kg 224Ra-solution
      group. CONCLUSION: Radium-224-solution containing chelated 212Pb is a promising
      candidate for the treatment of breast cancer patients with bone metastases.

PMID- 29599311
TI  - Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and
      Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.
AB  - We compared the status of stromal podoplanin-positive cancer-associated
      fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node
      metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in
      203 patients with human epidermal growth factor receptor 2-positive breast
      carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM,
      respectively. ppCAFs were most frequently found in tumors and corresponding LNM
      (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired
      tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were alpha-smooth
      muscle actin-positive and cluster of differentiation 21 protein-negative,
      suggesting them not to be resident lymph node cells. Moreover, in our series, the
      presence of ppCAFs in tumors was borderline related to poor disease-free survival
      (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs
      accompany metastatic cancer cells migrating from tumor to LNMs.

PMID- 29599312
TI  - In Vitro Elucidation of Drug Combination Synergy in Treatment of Pancreatic
      Ductal Adenocarcinoma.
AB  - BACKGROUND/AIM: Advances in therapies targeting proteins and pathways affected by
      genetic alterations has raised the possibility of personalized cancer treatments.
      MATERIALS AND METHODS: The efficacy of targeting molecular aberrations was
      determined in the pancreatic ductal adenocarcinoma (PDAC) cell line, CAPAN2. Two
      mutations were targeted, KRAS (p.G12V) and ABL1 (p.G1060D), and cells were
      treated with regorafenib and trametinib, individually and in combination.
      RESULTS: Exposure to either drug significantly increased cell death compared to
      the current standard of care, gemcitabine. Treatment with combinations of the
      drugs led to significant increases in cell death compared to either monotherapy.
      Strong additive/synergistic interactions were observed across a range of dosages
      and ratios, reducing dose requirements with potential clinical relevance.
      CONCLUSION: The data obtained in this PDAC cell model: i) support the use of
      matched monotherapies; ii) indicate the effectiveness of matched combination
      therapies; and iii) provide potential proof-of-concept for precision medicine
      approach to cancer treatment.

PMID- 29599313
TI  - The Novel Selective Pan-TRK Inhibitor ONO-7579 Exhibits Antitumor Efficacy
      Against Human Gallbladder Cancer In Vitro.
AB  - We previously reported that brain-derived neurotrophic factor (BDNF)/neurotrophic
      receptor tyrosine kinase 2 (NTRK2/TRKB) signaling contributes to induction of
      malignant phenotype of gallbladder cancer (GBC). Recently, pan-TRK inhibitors
      have been evaluated and their dramatic clinical activity is being shown for a
      variety of cancer types harboring an NTRK rearrangement in phase I trials. ONO
      7579 is an oral pan-TRK inhibitor currently under investigation in phase I/II
      clinical trial for TRK-rearranged solid tumors. In this study, we evaluated the
      anticancer effect of ONO-7579 using GBC cells with or without KRAS mutant, NOZ,
      TYGBK-1. Our study showed that ONO-7579 had a suppressive effect on GBC
      proliferation in TYGBK-1, and on invasive potential and vascular endothelial
      growth factor expression in TYGBK-1 and NOZ. Our data indicated that ONO-7579
      could be a promising treatment option for patients with GBC.

PMID- 29599314
TI  - Correlation of Expression of Tenascin C and Blood Vessel Density in Non-small
      Cell Lung Cancers.
AB  - BACKGROUND/AIM: Non-small cell lung cancers are cancer diseases that rank second
      in terms of incidence and first in terms of mortality, worldwide. Stromal cells
      of these cancers express tenascin C (TNC) - hexameric glycoprotein, which is also
      expressed during foetal life. TNC is also observed in stromal cells of most human
      cancers. In some cancers, TNC was shown to influence proliferation and migration
      of cancer cells and angiogenesis. The aim of this work was to analyze the
      correlation of expression of TNC with the markers of vascular endothelial cells,
      CD31 and CD34, and clinicopathological data in NSCLC. MATERIALS AND METHODS:
      Archival paraffin blocks from 101 cases of NSCLC were used for the studies.
      Immunohistochemical reactions were carried out on paraffin sections using mouse
      monoclonal antibodies anti-TNC, anti-CD31 and anti-CD34, with the use of
      Autosteiner Link-48. RESULTS: Statistical analysis of the results showed positive
      correlation between TNC expression and CD31(+) and CD34(+) microvessel density
      (MVD) (r=0.456, p<0.0001; r=0.296, p<0.01, respectively). CONCLUSION: Based on
      the obtained results it can be concluded, that TNC may be involved in
      angiogenesis in NSCLC.

PMID- 29599316
TI  - The Role of MTHFR Genotype in Colorectal Cancer Susceptibility in Taiwan.
AB  - AIM: To evaluate the contribution of methylenetetrahydrofolate reductase (MTHFR)
      genotype to the risk of colorectal cancer (CRC) in Taiwan. MATERIALS AND METHODS:
      In this hospital-based case-control study, the role of MTHFR C677T (rs1801133)
      and A1298C (rs1801131) genotypes in determining CRC risk were investigated among
      362 patients with CRC and an equal number of age- and gender-matched healthy
      individuals. RESULTS: The percentages of CC, CT and TT genotypes for MTHFR
      rs1801133 were 64.1%, 29.8% and 6.1% in the CRC group and 51.1%, 37.0% and 11.9%
      in the control group, respectively (p for trend=0.0006). Analysis of the allelic
      frequency distribution showed that the variant T allele of MTHFR rs1801133
      conferred a lower CRC susceptibility than did the wild-type C allele (odds
      ratio(OR)=0.66, 95% confidence interval(CI)=0.52-0.84, p=4.32*10-5). For the gene
      lifestyle interaction, there were obvious protective effects of MTHFR rs1801133 T
      allele on the risk of CRC among non-smokers, ever smokers and non-alcohol
      drinkers, but not drinkers. CONCLUSION: MTHFR rs1801133 T allele serves as a
      predictive marker for CRC risk and future studies with larger samples and
      functional evaluation are warranted to validate the current findings.

PMID- 29599315
TI  - Melatonin Promotes Apoptosis of Oxaliplatin-resistant Colorectal Cancer Cells
      Through Inhibition of Cellular Prion Protein.
AB  - BACKGROUND/AIM: Drug resistance restricts the efficacy of chemotherapy in
      colorectal cancer. However, the detailed molecular mechanism of drug resistance
      in colorectal cancer cells remains unclear. MATERIALS AND METHODS: The level of
      cellular prion protein (PrPC) in oxaliplatin-resistant colorectal cancer (SNU
      C5/Oxal-R) cells was assessed. RESULTS: PrPC level in SNU-C5/Oxal-R cells was
      significantly increased compared to that in wild-type (SNU-C5) cells. Superoxide
      dismutase and catalase activities were higher in SNU-C5/Oxal-R cells than in SNU
      C5 cells. Treatment of SNU-C5/Oxal-R cells with oxaliplatin and melatonin reduced
      PrPC expression, while suppressing antioxidant enzyme activity and increasing
      superoxide anion generation. In SNU-C5/Oxal-R cells, endoplasmic reticulum stress
      and apoptosis were significantly increased following co-treatment with
      oxaliplatin and melatonin compared to treatment with oxaliplatin alone.
      CONCLUSION: Co-treatment with oxaliplatin and melatonin increased endoplasmic
      reticulum stress in and apoptosis of SNU-C5/Oxal-R cells through inhibition of
      PrPC, suggesting that PrPC could be a key molecule in oxaliplatin resistance of
      colorectal cancer cells.

PMID- 29599317
TI  - Transforming Growth Factor-Beta Produced by Non-small Cell Lung Cancer Cells
      Contributes to Lung Fibroblast Contractile Phenotype.
AB  - BACKGROUND/AIM: Fibroblasts can alter the extracellular matrix (ECM),
      contributing to cancer progression by providing a scaffold for cancer cells. The
      influence of lung cancer cells (LCCs) on lung fibroblast-mediated ECM alteration
      is not well understood. MATERIALS AND METHODS: After incubation in serum-free
      medium, LCC- or fibroblast-conditioned media were collected. The ECM alteration
      was assessed by collagen gel contraction assay. RESULTS: Both LCC-conditioned
      medium and exogenous transforming growth factor (TGF)-beta1 increased collagen
      gel contraction by lung fibroblasts. TGF-beta1 was produced in LCC-conditioned
      media at approximately 2 ng/ml. SB431542, a specific TGF-beta receptor kinase
      inhibitor, partially inhibited the collagen gel contraction that had been
      increased by LCC-conditioned media. Lung fibroblast-conditioned medium stimulated
      TGF-beta1 production from LCCs, whereas LCC-conditioned medium decreased
      fibroblast survival and alpha-smooth muscle actin expression by fibroblasts.
      CONCLUSION: Interaction between LCCs and lung fibroblasts through TGF-beta
      signaling induces fibroblasts to assume the contractile phenotype and may
      contribute to cancer progression.

PMID- 29599318
TI  - Lentiviral Vector-mediated Gene Transfer in Human Bladder Cancer Cell Lines.
AB  - BACKGROUND/AIM: Currently, treatment of non-muscle invasive bladder cancer causes
      significant deterioration in a patient's quality of life (QOL). Therefore,
      development of novel therapeutic options without the deterioration of QOL is very
      important. In this study, we assessed the anti-tumor effect of lentivirus
      mediated gene transfection of tumor-suppressor genes in human bladder cancer
      cells. MATERIALS AND METHODS: Lentiviral vectors that contained the tumor
      suppressor genes, p53, p16, and PTEN, were transfected into human bladder cancer
      cell lines, 5637, T24, 253J, and UMUC3, and the normal human uroepithelial cell
      line, SV-HUC-1. RESULTS: Significant growth inhibition was observed in bladder
      cancer cells on transfection with the p16 and PTEN vectors. However, the effect
      of the p53 vector was limited. In normal cells, the lentiviral vectors did not
      exhibit a significant growth inhibitory effect. CONCLUSION: Lentiviral vector
      mediated gene transfection is useful for the application of gene therapy in
      bladder cancers.

PMID- 29599319
TI  - Aberrant Expression of PIWIL1 and PIWIL2 and Their Clinical Significance in
      Ductal Breast Carcinoma.
AB  - BACKGROUND/AIM: P-Element-induced wimpy testis (PIWI) proteins in complex with
      PIWI-interacting RNA (piRNA) are involved in epigenetic regulation of gene
      expression in germline cells. Aberrant expression of piRNA and PIWI proteins have
      been identified in various types of tumour cells. The aim of this study was to
      evaluate the expression profiles of PIWI-like protein-1, -2 (PIWIL1 and PIWIL2),
      their immunohistochemical (IHC) characteristics in ductal breast cancer, and
      determine their correlation with clinicopathological parameters of this type of
      cancer. MATERIALS AND METHODS: Material for IHC studies comprised of 101 invasive
      ductal carcinoma (IDC) cases and 31 mastopathy tissues. Frozen fragments of
      paired tissue specimens (tumour and adjacent non-malignant breast tissue) taken
      from 55 patients with IDC and 18 samples of mastopathy were used for molecular
      studies using real-time polymerase chain reaction (RT-PCR). RESULTS: A
      statistically significantly higher level of PIWIL1 and PIWIL2 was found in IDC
      compared to mastopathy samples (p<=0.0001). Increased expression of PIWIL1 was
      correlated with increased PIWIL2 expression in breast cancer tissue.
      Surprisingly, PIWIL1 mRNA was detected only in cancer and mastopathy, but was not
      found in most normal breast tissues, although it is noteworthy that the PIWIL2
      mRNA level was statistically significantly lower in mastopathy and IDC samples
      compared to normal breast tissues. CONCLUSION: Our results affirm the hypothesis
      that reactivation of PIWI expression in various caner types is crucial for cancer
      development.

PMID- 29599320
TI  - MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK.
AB  - BACKGROUND: miR-96 is reported to inhibit reversion cysteine-rich Kazal motif
      (RECK), which is associated with tumor invasion, in solid cancer types (e.g.
      breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of
      this study is to clarify whether miR-96 is similarly associated with tumor
      invasion in colorectal cancer. MATERIALS AND METHODS: We performed western
      blotting to investigate the expression of RECK when miR-96 mimics or inhibitors
      were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was
      assessed by a reverse transcription polymerase chain reaction. An invasion assay
      was used to evaluate tumor invasion. RESULTS: The expression of RECK was
      inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by
      miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96
      mimics were shown to promote tumor invasion. CONCLUSION: miR-96 may be associated
      with tumor invasion through inhibition of RECK expression in colorectal cancer.

PMID- 29599321
TI  - Induction of Mitotic Catastrophe in Human Cervical Cancer Cells After
      Administration of Aloe-emodin.
AB  - BACKGROUND: Aloe-emodin is an anthraquinone with potential pharmacological
      properties, including numerous antitumor properties. The purpose of the study was
      to determine whether aloe-emodin induces mitotic death in cervical cancer cells.
      MATERIALS AND METHODS: Analysis of morphological changes as surrogate mitotic
      death indicators in HeLa cells was carried out using optical, fluorescence and
      electron microscopy. Viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2-5
      diphenyltetrazolium bromide reduction assay. Cell-cycle analysis was performed
      using flow cytometry. RESULTS: Aloe-emodin increased the number of multinucleate
      cells, giant and micronuclear cells. There was a concentration-dependent decrease
      in the mitotic index with a predominance of cells in the metaphase of the mitotic
      process and inhibition of division in the G2/M phase of the cell cycle. The
      presence of cells with abnormal mitosis and cells with injury to the division
      spindle was also demonstrated. CONCLUSION: Aloe-emodin induces mitotic
      catastrophe in cervical cancer cells.

PMID- 29599322
TI  - Crosstalk Between Androgen-sensitive and Androgen-insensitive Prostate Cancer
      Cells.
AB  - AIM: To investigate how androgen-sensitive LNCaP cells crosstalk with androgen
      insensitive DU145 or PC-3 cells. MATERIALS AND METHODS: The numbers of LNCaP
      cells were counted when co-cultured with DU145 or PC-3 cells and vise versa.
      Androgen receptor (AR) activity in LNCaP cells was examined by luciferase
      reporter assay after transfection with a luciferase reporter driven by PSA
      promoter in the presence of DU145 or PC-3 cells. Concentration of androgens in
      the medium was measured by liquid chromatography-mass spectrometry (LC-MS/MS).
      The ability of migration and invasion of PC-3 and DU145 cells was investigated
      using a 2-layer chamber, in the presence of LNCaP cells. RESULTS: Co-culture of
      LNCaP cells with DU145 cells resulted in the conversion of dehydroepiandrosterone
      (DHEA) to dihydrotestosterone (DHT), which stimulated cell proliferation and PSA
      promoter activity in LNCaP cells. The increased cell proliferation rate and AR
      activity, induced in LNCaP cells after DHT treatment, was further enhanced by co
      culture with DU145 cells. LNCaP cells also stimulated the proliferation of DU145
      and PC-3 cells, via secreting soluble factors. Finally, LNCaP cells promoted
      migration and invasion of PC-3 cells, in a co-culture system; however inhibited
      migration and invasion of DU145 cells. CONCLUSION: Crosstalk between androgen
      sensitive PCa cells and androgen-insensitive PCa cells might develop the
      progression of PCa.

PMID- 29599323
TI  - Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.
AB  - BACKGROUND/AIM: Gastric cancer is one of the most common malignant cancers with a
      poor prognosis and high mortality rate worldwide. Current treatment of gastric
      cancer includes surgery and chemotherapy as the main modalities, but the
      potentially severe side-effects of chemotherapy present a considerable challenge.
      Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect
      against a variety of cancer cells. The purpose of this study was to determine the
      anti-cancer activity of Galla chinensis and its main component gallic acid on
      human gastric adenocarcinoma cells. MATERIALS AND METHODS: MTT assay and cell
      death ELISA were used to determine the apoptotic effect of Gallic Chinensis and
      gallic acid on human gastric adenocarcinoma cells. To determine the pathway and
      relevant components by which gallic acid-induced apoptosis is mediated through,
      cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000.
      Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric
      adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5
      expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA
      reduced gallic acid-induced cell death. In addition, p53 was shown to be involved
      in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis
      in AGS cells. CONCLUSION: These results suggest that gallic acid has a potential
      role in the treatment of gastric cancer.

PMID- 29599324
TI  - PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.
AB  - BACKGROUND/AIM: The programmed death 1 (PD-1) receptor and its ligand (PD-L1)
      play pivotal roles in regulating host immune responses. However, the inhibitory
      effects of this pathway on the function of tumor infiltrating T lymphocytes in
      gastric adenocarcinoma patients are not well-defined. MATERIALS AND METHODS: We
      characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor
      infiltrating cells and analyzed the association between PD-1/PD-L1 expression and
      disease progression in a cohort of 60 patients with Helicobacter pylori
      infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19
      asymptomatic controls. RESULTS: Relative to controls, the expression of PD-1 on
      peripheral blood and tumor infiltrating T cells increased with disease
      progression. In vitro, T cells induced PD-L1 expression on primary gastric
      adenocarcinoma epithelial cells in an IFN-gamma-dependent manner, which in turn
      promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. CONCLUSION:
      This study provides evidence for a new therapeutic target in gastric
      adenocarcinoma patients.

PMID- 29599325
TI  - Blocking the Cleavage of Filamin A by Calpain Inhibitor Decreases Tumor Cell
      Growth.
AB  - BACKGROUND/AIM: Filamin A (FLNA) is the most abundant and widely expressed
      isoform of filamin in human tissues. It is cleaved by calpain at the hinge 1 and
      2 domains, producing a 90-kDa carboxyl-terminal fragment (FLNACT). Recently, it
      has been shown that FLNACT mediates cell signaling and transports transcription
      factors into the cell nucleus. However, the significance of cleavage of FLNA by
      calpain has not been studied in cancer cell growth. Calpeptin is a chemical
      inhibitor of both calpain 1 and 2 that cleaves FLNA. In this study, we questioned
      if inhibiting calpain using calpeptin would decrease tumor cell proliferation,
      migration, invasion, and colony formation. MATERIALS AND METHODS: Human melanoma
      (A7), prostate cancer (PC3), mouse fibrosarcoma (T241) and endothelial (MS1)
      cells were assayed for proliferation, migration, invasion and colony formation
      after treatment with calpeptin. Cell lysates were immunoblotted for FLNA and
      FLNACT Results: Calpeptin treatment of these cells resulted in a decreased
      production of FLNACT Calpeptin-treated human and mouse tumor cells displayed
      impaired proliferation, migration, and colony formation. CONCLUSION: These data
      suggest that the cleavage of FLNA by calpain is an important cellular event in
      the regulation of tumor cell growth.

PMID- 29599326
TI  - Association of Matrix Metalloproteinase-7 Genotypes to the Risk of Oral Cancer in
      Taiwan.
AB  - BACKGROUND/AIM: Matrix metalloproteinases (MMPs) play a critical role in
      inflammation and carcinogenesis, and the expression of mRNA MMP7 in oral squamous
      cell carcinoma tissues was higher than in the oral lichen planus or normal oral
      mucosa. However, the genotypic role of MMP7 has never been examined in oral
      cancer. Therefore, in the current study we aimed to examine the contribution of
      genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to oral
      cancer risk in Taiwan. MATERIALS AND METHODS: In this hospital-based case-control
      study, 788 patients with oral cancer and 956 gender-and age-matched healthy
      controls were genotyped for MMP7 A-181G and C-153T via polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The
      distribution pattern of AA, AG and GG for MMP7 promoter A-181G genotype was 88.2,
      10.4 and 1.4% in the oral cancer patient group and 89.0, 9.3 and 1.7% in the
      healthy control group, respectively (p for trend=0.6779), non-significantly
      differentially distributed between the two groups. There is no polymorphic
      genotype for MMP7 C-153T among Taiwanese. The comparisons in allelic frequency
      distribution also support the findings that G allele may not be the risk
      determinant allele for oral cancer. There is no interaction between the genotypes
      of MMP7 with age, gender, smoking, alcohol or betel quid consumption on oral
      cancer risk. CONCLUSION: Our results indicate that the MMP7 promoter genotypes
      only play an indirect role in determining the personal susceptibility to oral
      cancer in Taiwan.

PMID- 29599327
TI  - Detection of EGFR Gene Mutation by Mutation-oriented LAMP Method.
AB  - BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) is a target of molecular
      therapeutics for non-small cell lung cancer. EGFR gene mutations at codons 746
      753 promote constitutive EGFR activation and result in worst prognosis. However,
      these mutations augment the therapeutic effect of EGFR-tyrosine kinase inhibitor.
      Therefore, the detection of EGFR gene mutations is important for determining
      treatment planning. The aim of the study was to establish a method to detect EGFR
      gene mutations at codons 746-753. MATERIALS AND METHODS: EGFR gene mutation at
      codons 746-753 in six cancer cell lines were investigated. A loop-mediated
      isothermal amplification (LAMP)-based procedure was developed, that employed
      peptide nucleic acid to suppress amplification of the wild-type allele. RESULTS:
      This mutation-oriented LAMP can amplify the DNA fragment of the EGFR gene with
      codons 746-753 mutations within 30 min. Moreover, boiled cells can work as
      template resources. CONCLUSION: Mutation oriented-LAMP assay for EGFR gene
      mutation is sensitive on extracted DNA. This procedure would be capable of
      detecting EGFR gene mutation in sputum, pleural effusion, broncho-alveolar lavage
      fluid or trans-bronchial lung biopsy by chair side.

PMID- 29599328
TI  - Chemo-sensitivity of Two-dimensional Monolayer and Three-dimensional Spheroid of
      Breast Cancer MCF-7 Cells to Daunorubicin, Docetaxel, and Arsenic Disulfide.
AB  - BACKGROUND/AIM: Chemo-sensitivity of two-dimensional (2D) monolayers and three
      dimensional (3D) spheroids of human breast cancer MCF-7 cells were investigated.
      MATERIALS AND METHODS: MCF-7 cells were cultured in monolayers or spheroids
      established using a thermo-reversible gelatin polymer, in the presence of
      daunorubicin, docetaxel, or As2S2 Cell proliferation was examined by a Cell
      Counting Kit-8 assay. RESULTS: Daunorubicin, docetaxel, and As2S2 dose
      dependently decreased the MCF-7 cell proliferation in both 2D- and 3D-culture
      systems. The 3D spheroids were less sensitive to these agents than the 2D
      cultured cells. Verapamil, an inhibitor of P-glycoprotein, partially enhanced the
      antiproliferative effects of the agents. DL-buthionine-(S, R)-sulfoximine
      significantly increased (p<0.05), while N-acetyl-L-cysteine significantly
      inhibited the antiproliferative effects of As2S2 (p<0.003). CONCLUSION: The 3D
      spheroids showed less sensitivity to the antiprolliferative efficacies of
      anticancer agents than the 2D cultured cells. P-Glycoprotein is suggested to be
      partially implicated in drug resistance. Reduction of cellular glutathione level
      enhanced the As2S2 cytotoxicity.

PMID- 29599329
TI  - Additional Nodal Disease Prediction in Breast Cancer with Sentinel Lymph Node
      Metastasis Based on Clinicopathological Features.
AB  - AIM: The standard-of-care in breast cancer (BC) with positive sentinel lymph node
      (SLN) metastasis includes complete axillary lymph node dissection (ALND);
      however, almost half of such cases have no further tumor burden. This study aimed
      to assess the clinicopathological factors that predict non-SLN metastasis to
      define subgroups of SLN-positive patients in whom the axilla may be staged by SLN
      biopsy alone, while avoiding unnecessary overtreatment. PATIENTS AND METHODS: The
      records of 191 patients with histologically-proven primary BC who underwent a
      positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least
      one tumor-involved SLN who underwent completion ALND were enrolled. Demographic
      and clinicopathological characteristics, including age, primary tumor size and
      histological grade, lymphovascular invasion, ratio of positive SLNs to the
      harvested SLNs, SLN metastasis size, and molecular subtype classification
      according to immunohistochemical biomarker status [estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)],
      were evaluated. Data were collected retrospectively and analyzed using the Mann
      Whitney and Chi-square tests (statistical significance: p<0.05). RESULTS: The
      incidence of non-SLN metastasis associated with positive SLN was 48.6% (93/191).
      The risk of additional nodal spread correlated with high sentinel nodal ratio
      >0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2
      overexpression (OR=0.4, p=0.016), and ER+PR-HER2- profile (OR=2.95, p=0.027).
      There was a tendency (statistically insignificant; p>0.05) toward higher
      incidence of non SLN metastasis with increasing age and histological grade, which
      could be attributed to the small sample size. CONCLUSION: According to this
      study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status
      significantly predicted the likelihood of additional lymphatic involvement.
      Validation of these parameters in prospective studies is indicated, and may help
      individualize treatment modalities.

PMID- 29599330
TI  - Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti
      apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In
      Vivo.
AB  - BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes
      sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro.
      However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC
      in vivo is unknown. The aim of the present study was to verify the anticancer
      effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND
      METHODS: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib,
      amentoflavone, or combination for 14 days, respectively. Effect of sorafenib,
      amentoflavone, or their combination on tumor growth, anti-apoptotic potential,
      apoptotic signaling and general toxicity were evaluated with digital caliper,
      immunohistochemistry staining and body weight. RESULTS: Our results demonstrated
      that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and
      expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to
      single-agent treatment. Additionally, amentoflavone also triggered sorafenib
      induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION:
      Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti
      apoptotic potential and induction of apoptosis in HCC in vivo.

PMID- 29599331
TI  - Isochlorogenic Acid C Reverses Epithelial-Mesenchymal Transition via Down
      regulation of EGFR Pathway in MDA-MB-231 cells.
AB  - BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) has been suggested to
      play an important role in survival, proliferation, migration, differentiation,
      and tumorigenesis of many cell types. Breast cancer patients with high EGFR
      expression have a poor prognosis. In this study, we investigated the molecular
      mechanism of the inhibitory effect of isochlorogenic acid c (ICAC) extracted from
      Lonicera japonica on elevated EGFR levels of the triple-negative breast cancer
      (TNBC) cell line, MDA-MB-231. MATERIALS AND METHODS: The cell viability and cell
      cycle analysis were evaluated using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl
      2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. The
      migration ability and invasiveness of ICAC-treated MDA-MB-231 were examined by
      migration and Matrigel invasion assay. The epithelial-mesenchymal-transition
      (EMT)-related protein expression was examined by western blotting and reverse
      transcriptase-polymerase chain reaction (RT-PCR). RESULTS: ICAC led to
      significant morphological changes and suppressed migration and invasion
      capacities of highly metastatic MDA-MB-231 cells. Western blot analysis for
      EGFR/EMT-associated proteins suggested that ICAC attenuated the mesenchymal
      traits as observed by up-regulation of epithelial markers and down-regulation of
      mesenchymal markers as well as decreased activities of matrix metalloproteinase-9
      (MMP-9). CONCLUSION: These results suggested that the inhibitory effects of ICAC
      against EGFR-induced EMT and MDA-MB-231 cell invasion were dependent on the EGFR/
      phospholipase Cgamma (PLCgamma)/extracellular regulated protein kinase 1/2
      (ERK1/2)/slug signaling pathway. Therefore, the obtained results could provide us
      clues for the next therapeutic strategy in the treatment of TNBC.

PMID- 29599332
TI  - Phenethyl Isothiocyanate Induces Apoptotic Cell Death Through the Mitochondria
      dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In
      Vitro.
AB  - BACKGROUND/AIM: Some lung cancer patients treated with gefitinib develop
      resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl
      isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits
      anticancer activities in many human cancer cell lines. Currently, there is no
      available information on the possible modification of gefitinib resistance of
      lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant
      lung cancer NCI-H460 cells were investigated in vitro. MATERIALS AND METHODS: The
      total cell viability, apoptotic cell death, production of reactive oxygen species
      (ROS) and Ca2+, levels of mitochondria membrane potential (DeltaPsim) and caspase
      3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced
      chromatin condensation was examined by DAPI staining. RESULTS: PEITC-induced cell
      morphological changes, decreased total viable cell number and induced apoptotic
      cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in
      NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased
      Ca2+ production, decreased the levels of DeltaPsim and increased caspase-3, -8
      and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was
      used to examine the effect of apoptotic cell death associated protein expression
      in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC
      increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro
      apoptotic protein Bax in NCI-H460/G cells. CONCLUSION: Based on these results, we
      suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria
      dependent pathway in NCI-H460/G cells.

PMID- 29599333
TI  - Frequency of the Loss of Heterozygosity of the NF2 Gene in Sporadic Spinal
      Schwannomas.
AB  - BACKGROUND/AIM: Individuals with type 2 Neurofibromatosis are predisposed for the
      appearance of schwannomas. In the present study we analyzed the loss of
      heterozygosity and mutations in the NF2 gene in patients with sporadic Schwannoma
      without Neurofibromatosis type 2. MATERIALS AND METHODS: We analyzed 39 patients
      with sporadic spinal schwannoma. We quantified the number of alleles by FISH and
      sequenced the NF2 gene. RESULTS: We identified 16/39 patients with point
      mutations and/or LOHs in the tumor samples analyzed. The LOHs were found in 7/39
      patients. Two homozygous mutations were detected in 4/39 tumors, and the presence
      of the mutation in heterozygosis was revealed in 3/39 patients. In two tumors, we
      detected the loss of one allele of the NF2 gene, with no mutation. CONCLUSION:
      The genetic alterations observed in the NF2 gene indicated that spinal
      schwannomas are associated with genetic alterations also found in other
      schwannomas and type 2 Neurofibromatosis, which reinforces the etiological role
      of this gene.

PMID- 29599334
TI  - Evaluation of Shape and Textural Features from CT as Prognostic Biomarkers in Non
      small Cell Lung Cancer.
AB  - BACKGROUND/AIM: We retrospectively investigated the prognostic potential
      (correlation with overall survival) of 9 shape and 21 textural features from non
      contrast-enhanced computed tomography (CT) in patients with non-small-cell lung
      cancer. MATERIALS AND METHODS: We considered a public dataset of 203 individuals
      with inoperable, histologically- or cytologically-confirmed NSCLC. Three
      dimensional shape and textural features from CT were computed using proprietary
      code and their prognostic potential evaluated through four different statistical
      protocols. RESULTS: Volume and grey-level run length matrix (GLRLM) run length
      non-uniformity were the only two features to pass all four protocols. Both
      features correlated negatively with overall survival. The results also showed a
      strong dependence on the evaluation protocol used. CONCLUSION: Tumour volume and
      GLRLM run-length non-uniformity from CT were the best predictor of survival in
      patients with non-small-cell lung cancer. We did not find enough evidence to
      claim a relationship with survival for the other features.

PMID- 29599335
TI  - Hyperforin Suppresses Tumor Growth and NF-kappaB-mediated Anti-apoptotic and
      Invasive Potential of Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: Previous studies have indicated that hyperforin inhibits tumor
      growth of hepatocellular carcinoma. However, the anticancer effects of hyperforin
      in non-small cell lung cancer (NSCLC) are ambiguous. The aim of the present study
      was to investigate the anticancer effect of hyperforin in NSCLC. NSCLC CL1-5-F4
      cells were treated with different concentrations of hyperforin or NF-kappaB
      inhibitor (QNZ) for different time periods. MATERIALS AND METHODS: Change of cell
      viability, NF-kappaB activation, apoptotic signaling pathways, expression of anti
      apoptotic proteins, and cell invasion were detected using the 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, NF-kappaB
      reporter gene assay, flow cytometry, western blotting, and cell invasion assay.
      RESULTS: The results demonstrated that hyperforin significantly promotes
      extrinsic and intrinsic apoptotic pathways, and inhibits cell viability and NF
      kappaB activation. In addition, results also indicated that blockage of NF-kappaB
      activation reduces the levels of anti-apoptotic proteins and cell invasion in CL1
      5-F4 cells. CONCLUSION: These results suggested hyperforin induces apoptosis and
      inhibits NF-kappaB-modulated anti-apoptotic and invasive potential in NSCLC.

PMID- 29599336
TI  - Glycine Is a Predictor for a Suppressive Effect of Fucoxanthinol on Colonosphere
      Formation Under Hypoxia.
AB  - BACKGROUND/AIM: Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to
      inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their
      sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are
      essential to maintain the stemness of CCSCs. We investigated effects of FxOH on
      sphere formation, intercellular energy metabolites in colonospheres formed from
      human colorectal HT-29 cells under hypoxic conditions. RESULTS: FxOH at 50 MUM
      suppressed HIF1alpha expression and activation of integrin, mitogen-activated
      protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and
      activator of transcription (STAT) signals. Moreover, expression of epithelial
      mesenchymal transition- and apoptosis-related proteins in the colonospheres was
      lowered by FxOH. The level of glycine was reduced in hypoxic colonospheres under
      FxOH treatment. CONCLUSION: FxOH attenuated the sphere formation of hypoxic
      colonospheres, in part, by suppressing HIF1alpha expression. Glycine could be a
      potential predictor for the activity of agents that inhibit sphere formation by
      hypoxic colonospheres.

PMID- 29599337
TI  - The Association of Matrix Metalloproteinase-8 Promoter Genotypes in Breast
      Cancer.
AB  - BACKGROUND/AIM: The family of matrix metalloproteinases (MMPs) controls
      homeostasis of the extracellular matrix and their genetic polymorphisms may be
      associated with personal cancer susceptibility. The serum levels of MMP8 was
      reported to be higher in patients with breast cancer than in healthy individuals.
      In this study, we aimed to investigate the contribution of a polymorphism in the
      promoter region of MMP8 (-799C/T) and two nonsynonymous polymorphisms (Val436Ala
      and Lys460Thr) to breast cancer. MATERIALS AND METHODS: MMP8 -799C/T, Val436Ala
      and Lys460Thr polymorphic genotypes were determined for 1,232 patients with
      breast cancer and 1,232 healthy controls by polymerase chain reaction-restriction
      fragment length polymorphism methodology. RESULTS: The odds ratios (ORs) after
      adjusting for age, gender, smoking and alcohol drinking status for those carrying
      CT and TT genotypes at the MMP8 promoter C-799T were 1.03 (95% CI=0.88-1.23,
      p=0.7475) and 1.08 (95% CI=0.91-1.53, p=0.3561), respectively, compared to those
      carrying the wild-type CC genotype. The OR for the combined T-bearing genotypes
      were of a similar non-significant level (OR=1.05, 95% CI=0.90-1.26, p=0.5176).
      Supporting this finding, the adjusted OR for those carrying the T allele at MMP8
      C-799T was 1.05 (95% CI=0.86-1.21, p=0.3797), compared to those carrying the wild
      type C allele. There was also no significant association of MMP8 Lys460Thr with
      breast cancer. There was no polymorphic genotype at MMP8 Val436Ala found among
      any of the investigated individuals. CONCLUSION: MMP8 -799C/T, Val436Ala and
      Lys460Thr polymorphisms may only play an indirect role in determining personal
      cancer susceptibility to breast cancer in Taiwan.

PMID- 29599338
TI  - TRAP1 Inhibition Increases Glutamine Synthetase Activity in Glutamine Auxotrophic
      Non-small Cell Lung Cancer Cells.
AB  - BACKGROUND/AIM: Cancer cells are distinct in terms of glutamine dependence. Here
      we investigated the different susceptibility of glutamine-independent and
      glutamine-dependent non-small cell lung cancer (NSCLC) to treatment with tumor
      necrosis factor receptor-associated protein 1 (TRAP1) inhibitor gamitrinib
      triphenylphosphonium (G-TPP). MATERIALS AND METHODS: Cell viability and
      proliferation under glutamine deprivation and G-TPP treatment were determined by
      the MTT and colony-formation assays. Protein and mRNA expression were determined
      by western blot and quantitative polymerase chain reaction. Colorimetric-based
      assay was performed to check for glutamine synthetase (GS) activity. RESULTS:
      NSCLC cells showed diverse adaptation under glutamine-depleted condition and were
      categorized into glutamine-independent and glutamine-dependent cells. Treatment
      with G-TPP particularly increased GS activity and induced cell death due to
      energy shortage indicated by phosphorylated AMP-activated protein kinase (AMPK)
      in glutamine-dependent cells. CONCLUSION: This finding provides better
      understanding of TRAP1-mediated glutamine metabolism through GS activity, and
      evidence that TRAP1 could be a promising therapeutic target for glutamine
      addicted cancer.

PMID- 29599339
TI  - Depth of Muscularis Propria Invasion Does Not Prognosticate Survival in T2
      Esophageal Adenocarcinoma.
AB  - AIM: Although tumor depth of invasion is strongly associated with risk of lymph
      node metastasis and long-term survival in patients with esophageal
      adenocarcinoma, the significance of differential T2 invasion (inner circular
      layer versus outer longitudinal layer) is unknown. The current study was
      undertaken to explore the hypothesis that greater T2-specific depth of invasion
      is associated with inferior long-term outcomes in patients with esophageal
      adenocarcinoma treated with esophagectomy. PATIENTS AND METHODS: Demographic,
      treatment, and outcome data were collected for patients with resected pT2N0-3M0
      esophageal adenocarcinoma treated between 2005 and 2015 pooled from four U.S.
      academic medical centers. Two blinded pathologists evaluated depth of muscularis
      propria tumor invasion. Univariate and Cox proportional hazard regression
      analyses were performed to identify prognostic factors for overall (OS) and
      disease-free (DFS) survival, and Kaplan-Meier analysis to compare survival
      differences specific to prognostic factors. RESULTS: A total of 84 patients were
      identified for analysis (53 with circular invasion; 31 with longitudinal
      invasion), with a median age of 66 years. Sixty percent of patients (50/84)
      received induction therapy prior to esophagectomy. The median OS and DFS was 58
      months (95% confidence interval(CI)=42 months-not reached) and 27 months (95%
      CI=13.7-66 months) respectively. Depth of muscularis propria invasion did not
      correlate with OS or DFS on univariate (p=0.42; and p=0.34, respectively) or
      multivariate (p=0.15 and p=0.21, respectively) analysis after adjustment for age,
      nodal status, perineural invasion, and tumor grade. These findings did not vary
      by induction therapy status. CONCLUSION: Depth of muscularis propria invasion
      does not appear to correlate with survival in patients with esophageal
      adenocarcinoma.

PMID- 29599340
TI  - Myelodysplastic Syndrome and Sweet's Syndrome Are Associated with a Mutation in
      Isocitrate Dehydrogenase 1.
AB  - BACKGROUND: Sweet's syndrome (SS) is a febrile neutrophilic dermatosis that has
      been clinically linked to hematological malignancies, particularly
      myelodysplastic syndrome (MDS), in a number of case series. Many epigenetic
      changes underlying MDS have been identified, such as a mutation in the isocitrate
      dehydrogenase 1 (IDH1) gene, which causes DNA hypermethylation and alteration of
      a number of genes that lead to leukemogenesis. However, the pathogenesis of
      malignancy-associated SS is unknown. CASE REPORT: We present two patients who
      were diagnosed with SS and concomitant IDH1-mutated MDS. Immunohistochemical
      staining of their skin lesions showed neutrophils diffusely positive for the IDH1
      mutation. CONCLUSION: These cases demonstrate that IDH1 mutation may be
      implicated in the pathogenesis of malignancy-associated SS. Future investigation
      to elucidate this pathway is warranted. Establishing this molecular link can
      provide an earlier identification of patients with SS who are also at increased
      risk for developing MDS.

PMID- 29599341
TI  - Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography
      in Patients with Early-stage Breast Cancer.
AB  - BACKGROUND: Early electrocardiogram (ECG) changes after breast cancer
      radiotherapy (RT) have been reported, but their characteristics and associated
      factors are largely unknown. This study aimed to explore early RT-induced ECG
      changes and to compare them with echocardiography changes. MATERIALS AND METHODS:
      Sixty eligible patients with chemotherapy-naive left-sided and 20 with right
      sided breast cancer were evaluated with echocardiography, blood samples and ECG
      before and after RT. RESULTS: RT-induced ECG changes in the anterior leads. T
      Wave changes were most frequent. T-Wave decline was associated independently with
      patient age (beta=-0.245, p=0.005), mean heart radiation dose (beta=1.252,
      p=0.001) and global systolic strain rate change (beta=7.943, p=0.002). T-Wave
      inversion was associated independently with mean heart radiation dose
      (beta=0.143, p<0.001), global longitudinal strain change (beta=0.053, p=0.017)
      and posterior calibrated integrated backscatter (beta=-0.022, p=0.049).
      CONCLUSION: RT-induced ECG changes were prevalent and associated with functional
      and structural changes in echocardiography. ECG could be used for post-RT cardiac
      screening.

PMID- 29599342
TI  - WT1-pulsed Dendritic Cell Vaccine Combined with Chemotherapy for Resected
      Pancreatic Cancer in a Phase I Study.
AB  - BACKGROUND/AIM: Wilms' tumor 1 (WT1) is a tumor-associated antigen highly
      expressed in cancer. We examined the safety of WT1-peptide pulsed dendritic cell
      (WT1-DC) vaccine in combination with chemotherapy in patients with surgically
      resected pancreatic cancer. PATIENTS AND METHODS: Eight patients with resectable
      pancreatic cancer undergoing surgery either combined with S-1 or S-1 plus
      gemcitabine therapy were enrolled. Immunohistochemical analysis of WT1 was
      performed in 34 cases of pancreatic cancer. RESULTS: No serious side-effects were
      observed, except grade I fever in five and grade I reactions at the injection
      site in all patients. WT1-specific cytotoxic T-lymphocytes were detected in seven
      patients, and WT1 and human leukocyte antigen class I antigens were positive in
      all 34 cases. CONCLUSION: Our study clarified the safety and potential
      acquisition of immunity after vaccination targeting WT1. Further efficacy of WT1
      DC vaccine to improve prognosis would be determined by a prospective clinical
      trial for resectable pancreatic cancer.

PMID- 29599343
TI  - Feasibility and Immune Response of WT1 Peptide Vaccination in Combination with OK
      432 for Paediatric Solid Tumors.
AB  - BACKGROUND/AIM: Wilms' tumor 1 (WT1) peptide-based vaccination has been reported
      for its potential usefulness in targeting several cancers. The adjuvant drug OK
      432 is known to have potent immunomodulation and therapeutic properties when
      applied in cancer treatment and may, thus, be important to trigger the
      appropriate immunological response in paediatric patients with a solid tumor that
      are vaccinated with a WT1 peptide. PATIENTS AND METHODS: Paediatric patients with
      a solid tumor were vaccinated with a WT1 peptide and OK-432 once every 2 weeks,
      for a total of seven times. RESULTS: Of the 24 patients, 18 completed the
      scheduled vaccinations. Sixteen patients had local skin symptoms and/or fever. In
      1 patient, anaphylactic symptoms emerged at the time of the final injection, but
      these quickly subsided after the treatment. WT1-specific immunological responses
      were observed in 4 patients (22.2%). WT1 and HLA class I expression were
      confirmed in 100% and 85% of primary tumors, respectively. CONCLUSION: WT1
      peptide vaccine therapy combined with OK-432 appears to be relatively safe for
      children. However further studies in a larger number of patients are necessary to
      confirm its safety and efficacy.

PMID- 29599344
TI  - Racial Disparities in the Molecular Landscape of Cancer.
AB  - BACKGROUND/AIM: African Americans (AA) have the highest incidence and mortality
      of any racial/ethnic group in the US for most cancer types. Heterogeneity in the
      molecular biology of cancer, as a contributing factor to this disparity, is
      poorly understood. To address this gap in knowledge, we explored the molecular
      landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high
      grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. MATERIALS AND
      METHODS: DNA from formalin-fixed paraffin-embedded tumors was sequenced using
      next-generation sequencing. Additionally, we evaluated protein expression using
      immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for
      known ethnicity associations. RESULTS: Considering only pathogenic or presumed
      pathogenic mutations, as determined by the American College of Medical Genetics
      and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections
      for multiple comparisons, we found that CRC tumors from AA patients harbored
      significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase,
      catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA
      patients also appeared to harbor more mutations of mitogen-activated protein
      kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin
      receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast,
      CRCs from AA patients were likely to carry fewer mutations of ataxia
      telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF),
      including the V600E variant, than those from CC patients. Rates of
      immunohistochemical positivity for epidermal growth factor receptor (EGFR) and
      DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients
      than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more
      frequent in the AA than in the CC cohort, whereas in squamous cell lung
      carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the
      AA than in CC group. Moreover, HGG tumors from AA patients showed a trend toward
      harboring more mutations of protein tyrosine phosphatase non-receptor 11
      (PTPN11), than HGG tumors from the CC cohort. In contrast, mutations of
      phosphatase and tensin homolog (PTEN) and tumor protein 53 (TP53) appeared to be
      higher in HGG tumors in CC patients than in their AA counterparts. CONCLUSION:
      Our data revealed significant differences and trends in molecular signatures of
      the three cancer types in AA and CC cohorts. These findings imply that there may
      be differences in carcinogenesis between AA and CC patients and that race may be
      a factor that should be considered regarding cancer incidence and outcome.

PMID- 29599345
TI  - Significance of Perioperative Chemotherapy in Squamous Cell Carcinoma of the
      Upper and Lower Urinary Tract.
AB  - BACKGROUND/AIM: To evaluate the clinicopathological characteristics and prognosis
      of squamous cell carcinoma (SCC) of the urinary tract (UT) urothelium, and
      investigate the utility of perioperative chemotherapy. PATIENTS AND METHODS:
      Thirty-three patients diagnosed with SCC in renal pelvis, ureter and bladder at
      the Kanazawa University between 2007 and 2017 were included in this retrospective
      study. Cancer-specific survival (CSS) rates according to cancer stage and
      neoadjuvant chemotherapy (NAC) were determined. RESULTS: Among the entire cohort,
      two-year CSS rates were 100%, 75%, 47% and 0% in stages I, II, III and IV,
      respectively, with a significant correlation between CSS and cancer stage
      (p=0.0063). Sixteen patients underwent radical surgery, and seven patients
      received NAC; however, there were no significant differences in CSS rates among
      patients stratified by NAC (p=0.7043). CONCLUSION: Worse cancer stage for SCC of
      UT urothelium was associated with worse prognosis. Given the poor efficacy of NAC
      in these patients, surgical treatment should be preferred.

PMID- 29599346
TI  - Bevacizumab Does Not Reduce the Lymphocele Rate in Advanced Ovarian Cancer After
      Complete Cytoreductive Surgery.
AB  - BACKGROUND/AIM: We aimed to evaluate the impact of bevacizumab on the lymphocele
      rate in patients after complete cytoreductive surgery for advanced ovarian
      cancer. PATIENTS AND METHODS: This retrospective study included patients with
      advanced ovarian cancer who had undergone complete cytoreductive surgery with
      pelvic and para-aortic lymphadenectomy at the Gustave Roussy Institute from 2005
      to 2014. The introduction of bevacizumab was discussed in a multidisciplinary
      meeting. RESULTS: During the study period, 247 patients were included; 24.6% of
      patients (61 patients) received adjuvant bevacizumab. The rate of symptomatic
      lymphocele was 34% (84 patients). In the lymphocele group, patients tended to
      receive adjuvant bevacizumab more often than did the control group (32% and 21%,
      respectively, p=0.05). In multivariate analysis, bevacizumab was not
      significantly associated with the risk of symptomatic lymphocele (hazard
      ratio(HR)=1.62, 95% confidence interval(CI)=0.87-3.01, p=0.12). CONCLUSION:
      Adjuvant bevacizumab has no impact on the formation or duration of symptomatic
      lymphocele in patients after complete cytoreductive surgery for advanced ovarian
      cancer.

PMID- 29599347
TI  - Morphological Classification of Corrupted Colonic Crypts in Ulcerative Colitis.
AB  - BACKGROUND/AIM: In ulcerative colitis (UC) the colonic mucosa shows, in addition
      to a high number of inflammatory cells, crypts with architectural distortions,
      called corrupted colonic crypts (CCC). Here we classify the histologic repertoire
      and assess the frequency of CCC in UC. PATIENTS AND METHODS: Five-hundred and
      sixteen histologic sections from 29 colectomy specimens with UC (24 having
      adenocarcinoma and five, high-grade dysplasia, HGD) were reviewed. RESULTS: The
      vast majority of the colonic mucosa portrayed countless crypts with normal shapes
      (CNS) lined with normal epithelium, except for 45 CNS: 28 showed inconclusive
      suspected cellular changes (ISCC), and 17, high-grade dysplasia (HGD). CCC were
      subdivided into four groups: i) Crypts with fission distortions, ii) Crypts with
      length distortions, iii) Crypts with outline distortions and iv) Crypts with
      axial polarity distortions. The most frequent CCC group had axial polarity
      distortions (33.4%), and the less frequent CCC group, outline distortions (21.1%)
      (p<0.05). No apparent differences in frequency between groups were found in
      colectomies with HGD/carcinoma, or in colectomies preformed for medically
      refractory UC without HGD/carcinoma. Out of the 902 CCC present in the specimens,
      343 (38.0%) displayed ISCC, 186 (20.6%) HGD, and the remaining 373 (41.4%) normal
      epithelium. Hence, of the 203 crypts exhibiting HGD, 186 (91.6%) were CCC and the
      remaining 17 (8.4%) CNS (p<0.05). CONCLUSION: Based on these findings it is
      suggested that the microscopic search for HGD in UC colectomy-specimens should
      preferentially be focused on mucosal areas exhibiting CCC. This view is validated
      by recent findings showing that p53 overexpression (a biomarker of epithelial
      carcinogenesis) significantly correlated with architectural distortions of the
      crypts in UC.

PMID- 29599348
TI  - Expression of Estrogen Receptor-alpha and Survival in Advanced-stage Non-small
      Cell Lung Cancer.
AB  - BACKGROUND/AIM: The favorable prognosis of women with non-small-cell lung cancer
      (NSCLC) compared to men might be explained by sex hormone-related mechanisms. We
      investigated whether this observation could be explained by the expression of
      estrogen receptor-alpha (ER-alpha) in tumor tissue. MATERIALS AND METHODS:
      Archived, formalin fixed, paraffin embedded tumor tissue samples were
      retrospectively analyzed for nuclear expression of ER-alpha with
      immunohistochemistry. RESULTS: Biopsies from 222 patients were analyzed. Twenty
      three percent were ER-alpha positive. Fifty-four percent of the patients were men
      and 46% of the tumors were adenocarcinomas. One hundred-nine (49%) patients
      received pemetrexed and carboplatin and 113 (51%) received gemcitabine and
      carboplatin. Females with ER-alpha positive tumors who received PC had a
      substantial survival benefit over all other groups (20 vs. 4.6 months; p=0.003).
      CONCLUSION: ER-alpha is an independent prognostic factor in advanced NSCLC and
      might also be a predictive factor for response to pemetrexed/carboplatin in
      women.

PMID- 29599349
TI  - Patient-reported Symptom Burden, Rate of Completion of Palliative Radiotherapy
      and 30-day Mortality in Two Groups of Cancer Patients Managed With or Without
      Additional Care by a Multidisciplinary Palliative Care Team.
AB  - BACKGROUND/AIM: The aim of this study was to analyze differences in symptom
      burden, baseline and outcome parameters, including completion of palliative
      radiotherapy and 30-day mortality, between patients treated with palliative
      radiotherapy (RT) who were managed exclusively by regular oncology staff or a
      multidisciplinary palliative care team (MPCT) in addition. PATIENTS AND METHODS:
      This was a retrospective single-institution analysis. Comparison of two groups of
      patients: MPCT versus none (n=36 and 65, respectively). All patients provided
      Edmonton symptom assessment system (ESAS) data before RT. RESULTS: The MPCT group
      included significantly more patients with reduced performance status.
      Furthermore, these patients had higher ESAS symptom scores, except for two items
      (dyspnea, sleep). The largest differences were observed for pain, fatigue,
      anxiety and depression. The significant difference in pain scores was also
      reflected in different opioid medication rates. Failure to complete radiotherapy
      was more common in the MPCT group (11 and 2%, respectively, p=0.05). Thirty-day
      mortality was different, too (28 and 2%, respectively, p=0.0001). The Kaplan
      Meier survival curves were not significantly different (1-year survival rates 21
      and 25%, respectively, p=0.27). CONCLUSION: The MPCT group was characterized by a
      higher symptom burden. Prognostic factors such as performance status were not
      balanced between the two groups. Despite this fact, actuarial overall survival
      was comparable. Given the high rate of 30-day mortality in the MPCT group,
      efforts to optimize criteria for initiation of radiotherapy are warranted.

PMID- 29599350
TI  - Periapical Cemento-osseous Dysplasia Is Rarely Diagnosed on Orthopantomograms of
      Patients with Neurofibromatosis Type 1 and Is Not a Gender-specific Feature of
      the Disease.
AB  - : Several skeletal aberrations of the skull have been described for the tumor
      predisposition syndrome neurofibromatosis type 1 (NF1). Recently, periapical
      cemental/cemento-osseous dysplasia (COD) has been described in females affected
      with NF1. This reactive lesion of the hard tissues in tooth-bearing areas of the
      jaw has been proposed to represent a gender-specific radiological feature of NF1.
      The aim of this study was to investigate the prevalence of COD in patients with
      NF1. PATIENTS AND METHODS: The orthopantomograms (OPGs) of 179 patients with a
      confirmed diagnosis of NF1 were analyzed for COD. The results were compared to
      radiographic findings obtained in OPGs of age- and sex-matched controls. The NF1
      patient group was further differentiated according to the evidence of facial
      plexiform neurofibroma. RESULTS: COD was a very rare finding in both groups. The
      extension of the diagnostic criteria including radiologically-healthy teeth and a
      widened periodontal gap in the periapical area only marginally increased the
      number of considered cases. Although there was a somewhat more common occurrence
      of such changes in the patient group compared to the control group and the number
      of affected women was greater than the number of men, none of these differences
      reached statistical significance. Furthermore, COD or widening of the
      periradicular periodontal space was not found to be associated with facial tumor
      type in NF1. CONCLUSION: The investigation revealed that COD is not a diagnostic
      feature of NF1. There is no clear association of the rare finding of COD with
      gender. These studies should be compared with patient groups of other ethnic
      backgrounds.

PMID- 29599351
TI  - Analysis of HER Family (HER1-4) Expression as a Biomarker in Combination Therapy
      with Pertuzumab, Trastuzumab and Docetaxel for Advanced HER2-positive Breast
      Cancer.
AB  - BACKGROUND: Chemotherapy with trastuzumab, pertuzumab and docetaxel (TPD regimen)
      is now strongly recommended as a treatment option for first-line therapy for
      advanced human epidermal growth factor receptor (HER)2-positive breast cancer. In
      this study, we analyzed the expression of HER 1-4 proteins, and investigated
      whether or not their expression was predictive of the response of advanced HER2
      positive breast cancer to chemotherapy with the TPD regimen. PATIENTS AND
      METHODS: The study consisted of 29 cases in which TPD regimen chemotherapy was
      carried out from September 2013 to November 2015. The expression levels of
      estrogen receptor (ER), progesterone receptor (PgR), Ki67, HER1, HER2, HER3 and
      HER4 were evaluated using immunostaining employing needle biopsy specimens.
      RESULTS: The overall response rate (ORR) was significantly higher in the HER3
      positive group than in the HER3-negative group (p=0.002). In prognostic analysis,
      the HER3-positive group showed a significant progression-free survival extension
      over the HER3-negative group (p=0.042, log-rank). In univariate analysis,
      objective response (p=0.004, hazard ratio(HR)=0.123) and positive HER3 expression
      (p=0.023, HR=0.279) significantly contributed to extension of progression-free
      survival interval. CONCLUSION: HER3 expression may be a useful factor for
      predicting the response of HER2-positive breast cancer to chemotherapy with the
      TPD regimen.

PMID- 29599352
TI  - KDM4D Predicts Recurrence in Exocrine Pancreatic Cells of Resection Margins from
      Patients with Pancreatic Adenocarcinoma.
AB  - BACKGROUND/AIM: The role of histone demethylators, such as Jumonji domain 2
      (JMJD2/KDM4) proteins, and histone deacetylases, such as sirtuins (SIRT) is
      poorly characterized in pancreatic carcinomas while they have a major role in the
      carcinogenesis of several other tumours. MATERIALS AND METHODS: We assessed
      retrospectively with immunohistochemistry the expressions of KDM4A, KDM4B and
      KDM4D in 81 and SIRT1-4 in 102 pancreatic adenocarcinomas. Immunostaining was
      evaluated separately in benign pancreatic tissues and in malignant cells.
      RESULTS: High nuclear KDM4D expression in benign pancreatic tissue from resection
      margins associated with dismal disease-free survival (DFS) (OR=8.00; 95%CI=1.87
      33.9; p=0.005), even more significantly than tumour size and lymph node
      involvement. High cytoplasmic SIRT2 expression in benign pancreatic tissues also
      associated with a shorter DFS, but only in univariate analysis (p=0.026).
      CONCLUSION: Nuclear KDM4D and SIRT2 expression deviated from that of benign
      pancreatic tissue thus putatively influencing gene expression of tumor cells.
      Regardless, none of the enzymes studied had a decisive role in the spread of
      pancreatic cancer. A high nuclear expression of KDM4D in samples of pancreatic
      resection margins significantly and independently predicted an earlier recurrence
      and could thus be used in the assessment of risk of relapse in clinical practice.

PMID- 29599353
TI  - Long-term Results of External Beam Radiotherapy for Prostate Cancer with Prostate
      specific Antigen of More Than 50 ng/ml and Without Evidence of Lymph Node or
      Distant Metastasis.
AB  - BACKGROUND/AIM: To evaluate long-term treatment outcomes of external beam
      radiotherapy for prostate cancer with a pretreatment prostate-specific antigen
      (PSA) level of more than 50 ng/ml and without evidence of lymph node or distant
      metastasis. PATIENTS AND METHODS: Definitive radiotherapy of 66 Gy or 72 Gy in
      combination with androgen deprivation therapy (ADT) was performed. PSA relapse
      free survival (PRFS), distant metastasis-free survival (DMFS), cause-specific
      survival (CSS), and overall survival (OS) were evaluated. The impact of
      prognostic factors on PRFS, DMFS, CSS, and OS was analyzed in univariate and
      multivariate analyses. RESULTS: One hundred twenty patients with a median follow
      up period of 92.6 months were analyzed in this study. The median duration of ADT
      was 11.0 months. The 5- and 8-year PRFS rates in all patients were 65.1% and
      48.5%, respectively. The 8-year DMFS, CSS, and OS rates in all patients were
      84.0%, 93.4%, and 81.6%, respectively. Both in univariate and multivariate
      analyses, Gleason score (GS) and radiotherapy dose were significant prognostic
      factors (p=0.015 and 0.001). There was no significant difference between each
      prognostic factor in DMFS, CSS, and OS. CONCLUSION: We might have indicated the
      significance of definitive radiotherapy even for prostate cancer with PSA of more
      than 50 ng/ml and without evidence of metastasis.

PMID- 29599354
TI  - Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer by
      Subtype Using Tumor-infiltrating Lymphocytes.
AB  - BACKGROUND/AIM: Recent interest has focused on the significance of tumor
      infiltrating lymphocytes (TILs) on the efficacies and outcomes of the treatment
      in breast cancer (BC). Based on the recent international recommendation to
      standardize the evaluation method, the clinical validity and utility of TILs in
      patients who underwent neoadjuvant chemotherapy (NAC) were investigated in the
      present study. PATIENTS AND METHODS: TILs were evaluated in 177 patients with BC
      treated with NAC and subsequent curative surgery. The correlation between TILs
      evaluated according to the standard method and prognosis, including the efficacy
      of NAC, was investigated retrospectively. RESULTS: In the high-TIL group (n=96)
      compared to the low-TIL group (n=81), triple-negative breast cancer (TNBC)
      (p<0.001) and human epidermal growth factor receptor 2-enriched breast cancer
      (HER2BC) (p=0.040) were significantly more frequent, and the pathological
      complete response (pCR) rate was significantly higher (p=0.003). Among patients
      with TNBC and those with HER2BC, the pCR rate was significantly higher in the
      high-TIL group than in the low-TIL group (p=0.013 and p=0.014, respectively).
      Multivariable analysis also showed that high-TIL status was an independent factor
      predicting favorable prognosis (hazard ratio(HR)=0.24, p=0.023 and HR=0.13,
      p=0.036). Biopsy specimens from local recurrence after successful NAC frequently
      showed TILs decreased. CONCLUSION: TILs may be a biomarker for predicting
      treatment response to NAC in patients with TNBC and HER2BC. A decrease in TILs
      may also be associated with tumor recurrence.

PMID- 29599355
TI  - Innovations for Cervical Esophagogastrostomy in Thoracic Esophageal Cancer
      Operations.
AB  - Three-field lymph node dissection is now performed in operations for advanced
      thoracic esophageal cancer, with an associated improvement in outcomes. However,
      reconstructive surgery following resection of the esophagus is frequently
      associated with the occurrence of anastomotic leakage. Once it occurs, major
      problems can arise such as decreased quality of life, protracted hospitalization,
      or even death. This is why there has been a large number of innovations in and
      modifications to reconstructive surgery. The standard procedures in our
      Department for advanced thoracic esophageal cancer are subtotal esophagectomy and
      three-field lymph node dissection. The thin gastric tube along the greater
      curvature is used as the reconstructed organ in reconstructive surgery,
      performing a cervical esophagogastrostomy. Innovations have been made to
      reconstructive surgery in order to prevent anastomotic leakage. This procedure
      markedly reduces anastomotic leakage, and also reduces anastomotic stricture,
      which likely makes it an extremely useful procedure that any surgeon can perform.

PMID- 29599356
TI  - Prognostic Value of Albumin/Globulin Ratio in Patients with Upper Tract
      Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy.
AB  - BACKGROUND/AIM: We investigated the prognostic role of the albumin/globulin ratio
      (AGR) in patients with upper tract urothelial carcinoma (UTUC) undergoing radical
      nephroureterectomy (RNU). PATIENTS AND METHODS: AGR was calculated as follows:
      AGR=serum albumin/(serum total protein-serum albumin). Associations of
      preoperative AGR with disease-free (DFS) and overall (OS) survival were assessed
      in 105 patients with UTUC undergoing RNU. RESULTS: Patients with preoperative AGR
      <1.24 and >=1.24 were classified into the low (n=46, 44%) and high (n=59, 56%)
      groups, respectively. The 5-year DFS and OS were 77% and 78%, respectively. On
      multivariate analysis, high preoperative AGR was an independent predictor for
      both better DFS (hazard ratio(HR)=0.34, p=0.038) and OS (HR=0.24, p=0.006). The 5
      year DFS and OS were significantly longer in the high-AGR group than in the low
      AGR group (90% vs. 60%; 89% vs. 65%, both p<0.001). CONCLUSION: The AGR has
      prognostic value in patients with UTUC undergoing RNU.

PMID- 29599357
TI  - Gastric Cancer of "Crawling Type" Detected by Additional Gastrectomy After
      Endoscopic Submucosal Resection.
AB  - "Crawling type" gastric cancer (GC) is known as a rare variant of early GCs,
      which is difficult to diagnose at an early stage because of low-grade nuclear
      atypia and a morphology mimicking intestinal metaplasia. This is a case report of
      a 69-year-old woman who was diagnosed with early-stage gastric cancer. She had
      endoscopic submucosal resection (ESD) and histologically, both horizontal and
      vertical margins were negative. Seven months after ESD, a new lesion of the
      stomach was detected by follow-up gastroscopy. Laparoscopic distal gastrectomy
      was performed and "crawling type" glands were observed throughout the whole area
      of the tumor. We should keep this variant in mind, especially when a tumor is
      superficial depressed or superficial flat type in the middle of the stomach.
      Careful observation with multiple biopsies of all mucosal layer and a re-biopsy
      is the key procedure for obtaining the right diagnosis. Endoscopic and
      histological characteristics should also be reviewed.

PMID- 29599358
TI  - Numerical Imbalances of Chromosome 7 in Oral Squamous Cell Carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is an aggressive neoplasm. Many
      chromosomal and gene alterations have been identified in OSCC, including
      structural and numerical changes. In this study, we implemented a molecular assay
      of chromosome 7 (Chr7) in order to investigate the level of its numerical
      instability in OSCC. MATERIALS AND METHODS: Using tissue microarray technology,
      30 primary OSCCs were cored and re-embedded into one recipient block. Chromogenic
      in situ hybridization assay was performed based on Chr7 centromeric
      probedetection. RESULTS: Chr 7 numerical analysis detected polysomy (trisomy/
      tetrasomy) in 4/30 (13.3%) of the examined tissue OSCC cores. Statistical
      significance was assessed correlating Chr7 numerical aberrations with stage
      (p=0.015), especially detected in cases not related to human papillomavirus (HPV)
      (p=0.01). CONCLUSION: Although Chr7 polysomy is a relatively rare gross genetic
      event in OSSC, it affects their biological behavior leading toa progressively
      aggressive phenotype (advanced stage). Furthermore, Chr7 polysomy is observed
      more frequently in non-viral (HPV) cases.

PMID- 29599359
TI  - Clinicopathological Aspects and Diagnostic Problems in Patients with Intraductal
      Papillary Neoplasm of the Bile Duct.
AB  - BACKGROUND/AIM: Intraductal papillary neoplasm of the bile duct (IPNB) is defined
      as a non-invasive malignancy and disparity of its histological diagnosis with
      related diseases remains. PATIENTS AND METHODS: Twenty-six cases of IPNB and 12
      of papillary adenocarcinomas (PAC) at two Institutes were investigated. RESULTS:
      The prevalence of biliary dilatation and mucin secretion in the group with IPNB
      was significantly higher compared to the group with PAC (p<0.01). IPNB was
      predominantly located in the proximal bile duct compared to the location of PAC
      (p<0.01). Mis-matching of a second histological diagnosis was observed in 27% of
      IPNB and 25% of PAC, respectively. The prevalence of tumor relapse was
      significantly higher in PAC than in IPNB (p<0.05), and the overall survival was
      significantly better in IPNB than in PAC (p<0.01). CONCLUSION: Although IPNB is
      currently defined under histological criteria, morphologies were various and
      disparity in histological diagnosis for IPNB remains problematic when the
      clinical strategy is contemplated.

PMID- 29599360
TI  - Transient Exocrine Pancreatic Insufficiency: First Report of an Unrecognized
      Complication of Cytoreductive Surgery and HIPEC.
AB  - BACKGROUND: As cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for
      peritoneal surface malignancies, familiarity with this procedure's adverse events
      is also growing. Herein, we describe an unreported adverse event of exocrine
      pancreatic insufficiency (EPI) following CRS and HIPEC. PATIENTS AND METHODS:
      Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively
      recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in
      all patients in the immediate postoperative period. Patients with diarrhea who
      had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and
      their symptomatic progression was followed. RESULTS: A total of 26 patients were
      included. Eleven patients (42.31%) developed postoperative refractory diarrhea,
      nine of whom had a low FE1 level. These patients were treated with PERT either
      directly or after completion of antibiotics course if C. difficile toxin was
      positive. Eight patients demonstrated symptomatic resolution of their diarrhea,
      and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea
      had lower FE1 levels, and were more likely to have had a terminal ileum resection
      and had a longer hospital stay. Regression analysis identified the rapid rise of
      a patient's core temperature by >1 degrees C within 15 minutes as the sole
      predictor of EPI occurrence. CONCLUSION: EPI is a potential adverse event
      following CRS and HIPEC and might be largely responsible for refractory diarrhea.
      In our patients with refractory diarrhea and low FE1, PERT provided immediate
      symptomatic relief. The biological basis of this phenomenon remains unclear and
      warrants further investigation.

PMID- 29599361
TI  - The Clinical Usefulness of the LigaSureTM Small Jaw in Axillary Lymph Node
      Dissection in Patients with Breast Cancer.
AB  - BACKGROUND: The LigaSureTM small jaw (LS-SJ) multifunctional tissue sealing
      system is mainly used in cervical operations. We aimed to evaluate the clinical
      efficacy of the LS-SJ in axillary lymph node dissection (ALND) in comparison to
      the conventional method. PATIENTS AND METHODS: Ninety-two patients with breast
      cancer who underwent total mastectomy and ALND were included in this study. The
      patients were divided into the LS-SJ group (n=43) and the conventional-ALND (c
      ALND) group (n=49). RESULTS: Patients with high body mass index values had a
      greater drainage volume and longer time to drain removal. The drainage volume was
      in the LS-SJ group was significantly lower than that in the c-ALND group. The
      time to drain removal and the hospitalization period were also significantly
      shorter in the LS-SJ group. The LS-SJ was more effective for ALND in obese
      patients. CONCLUSION: The results suggest the clinical usefulness of LS-SJ in
      ALND in patients with breast cancer, especially in obese patients.

PMID- 29599362
TI  - Curative Gastrectomy with Perioperative Chemotherapy Improves the Survival for
      Unresectable Gastric Cancer.
AB  - BACKGROUND/AIM: Although there are a few reports recommending gastrectomy for
      unresectable gastric cancer (UGC) to improve survival, the advantage of
      gastrectomy remains unclear. The objective of this study was to assess the
      meanings of the surgical intervention. PATIENTS AND METHODS: Therapeutic outcomes
      were retrospectively evaluated in 127 patients with UGC. All patients had
      chemotherapy and 47 patients underwent gastrectomy. Patients were classified to
      three groups according to the treatment. RESULTS: Multivariate analysis showed
      that gastrectomy was in independent favorable prognosis factor (p<0.001) as well
      as performance status 0/1, differentiated type, absence of distant organ
      metastasis, and second line chemotherapy for UGC. Among the patients with
      gastrectomy, R0 resection was an independent prognostic factor (p=0.011). R0
      resection was mainly achieved when there was a single non-curable factor and no
      distant organ metastasis (p=0.007 and p=0.024, respectively). CONCLUSION:
      Gastrectomy has an advantage in improving the survival in selected cases among
      UGC. If chemotherapy enables to control the non-curable factors, gastrectomy
      should be considered.

PMID- 29599363
TI  - Effects of omega-3 Fatty Acid Supplementation in Patients with Bile Duct or
      Pancreatic Cancer Undergoing Chemotherapy.
AB  - BACKGROUND/AIM: Omega-3 fatty acids may improve cancer cachexia, but only in
      patients with pancreatic and bile duct cancer. Patients with pancreatic cancer
      commonly suffer from exocrine pancreatic insufficiency, and the ingestion of
      digestive enzyme supplements may improve absorption. PATIENTS AND METHODS:
      Racol(r), an enteral nutrient formulated with omega-3 fatty acids, was
      administered to patients with unresectable pancreatic and bile duct cancer. The
      skeletal muscle mass and blood test data were taken pre-administration and at 4
      and 8 weeks after. Patients with pancreatic cancer were given the digestive
      enzyme supplement LipaCreon(r) from the fifth week after the start of
      administration. RESULTS: In all 27 patients, skeletal muscle mass was
      significantly increased at both 4 and 8 weeks after the start of administration
      versus pre-administration (p=0.006, p=0.002, respectively). CONCLUSION: Omega-3
      fatty acid supplementation in patients with unresectable pancreatic and bile duct
      cancer may improve cancer cachexia.

PMID- 29599364
TI  - Tumor Enhancement on Dynamic CT: A Predictive Factor for Recurrence After
      Nephrectomy in Localized T1 Clear Cell Renal Cell Carcinoma.
AB  - AIM: To investigate whether radiological parameters obtained on dynamic computed
      tomography (CT), especially those related to tumor enhancement, are predictive
      factors for recurrence after nephrectomy in localized stage T1 clear cell renal
      cell carcinoma (ccRCC). MATERIALS AND METHODS: We retrospectively studied 88
      patients with localized stage T1 ccRCC who underwent dynamic CT preoperatively.
      Seven patients had recurrent disease after surgery. Tumor attenuations were
      measured by placing a region of interest in the solid region. TApre and TAneph
      were defined as the tumor attenuation values of the pre-contrast and
      nephrographic phase, respectively. The correlations between disease-free survival
      and clinicopathological factors, including the radiological parameter TAneph -
      TApre (DeltaTAneph), were analyzed by Cox proportional hazards model or Kaplan
      Meier method with the log-rank test. RESULTS: Only DeltaTAneph was significantly
      and positively correlated with disease-free survival (p<0.05). Tumor size also
      tended to be negatively correlated with disease-free survival (p<0.1). The 5- and
      10-year disease-free survival rates of the group with high DeltaTAneph (>=86 HU)
      were 97.4% and 97.4%, while those of the group with low DeltaTAneph (<86 HU) were
      89.6% and 71.6%, respectively. CONCLUSION: Tumor enhancement in the nephrographic
      phase of CT was a predictive factor for recurrence after nephrectomy in patients
      with localized stage T1 ccRCC.

PMID- 29599365
TI  - Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for
      Patients with Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: The purpose of this trial was to evaluate the feasibility and
      efficacy of alternating platinum-based doublet chemotherapy with epidermal growth
      factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR
      mutant non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy
      naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All
      patients underwent induction chemotherapy by sequentially alternating
      pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy
      with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion
      rate of the induction therapy. RESULTS: Eighteen eligible patients were enrolled
      between May 2011 and March 2016. The completion rate of induction therapy was
      72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury,
      but no other serious complications concerning this protocol were observed.
      Furthermore, diarrhea, rashes, and hematological adverse effects were mild.
      CONCLUSION: The completion rate of induction therapy was promising. Alternating
      chemotherapy and EGFR-TKIs should be further investigated regarding feasibility
      and efficacy.

PMID- 29599366
TI  - Performance Status and Number of Metastatic Extra-cerebral Sites Predict Survival
      After Radiotherapy of Brain Metastases from Thyroid Cancer.
AB  - BACKGROUND/AIM: Patients with brain metastases from thyroid cancer are extremely
      rare. This study evaluated clinical factors for survival following whole-brain
      radiotherapy (WBRT) alone. PATIENTS AND METHODS: In six patients, the following
      factors were analyzed for survival: Regimen of WBRT (5*4 Gy vs. 10*3 Gy), gender,
      age (<=55 vs. >=56 years), Karnofsky performance score (KPS) (60% vs. 70-80%),
      number of brain lesions (2-3 vs. >=4) and number of extra-cranial metastatic
      sites (one vs. more than one). RESULTS: KPS 70-80% (p=0.036) and involvement of
      only one extra-cranial site (p=0.018) were associated with better survival on
      univariate analysis. On Cox regression analysis, KPS (p=0.14) and number of extra
      cranial sites (p=0.14) showed trends for association with survival. In patients
      with KPS 70-80% and only one extra-cranial site, 6-month survival was 100%, no
      patient with KPS 60% and more than one extra-cranial site survived to 6 months.
      CONCLUSION: KPS and number of involved extra-cranial metastatic sites were
      associated with survival and may be helpful for individualizing therapy in
      patients with brain metastases from thyroid cancer.

PMID- 29599367
TI  - Cost-effectiveness of Multiparametric MRI in 800 Men Submitted to Repeat Prostate
      Biopsy: Results of a Public Health Model.
AB  - BACKGROUND/AIM: To evaluate the cost-effectiveness of multiparametric magnetic
      imaging resonance (mpMRI) in men submitted to repeat saturation prostate biopsy
      (SPBx). MATERIALS AND METHODS: From January 2011 to June 2017, 800 men underwent
      repeat SPBx; the cost-effectiveness of mpMRI if used as a 'triage test' to avoid
      unnecessary repeat prostate biopsy was retrospectively calculated using the
      Italian Public National Health System Day Service. RESULTS: SPBx vs. MRI fusion
      targeted biopsy diagnosed 215 (89.5%) vs. 184 (76.6%) out of 240, respectively.
      The overall cost of the 800 prostate biopsies was 138,221 ?; the use of mpMRI as
      triage test would have spared 364/800 procedures, equivalent to 60,905 ? (44% of
      the entire cost), whilst missing 15/205 (7.3%) cases of clinically significant
      cancer. CONCLUSION: mpMRI used as a triage test could reduce the need for
      prostate biopsies by about 45%, thereby improving cost-effectiveness, however,
      patients should be informed of the false-negative rate associated with mpMRI.

PMID- 29599368
TI  - Metformin-associated Chemopreventive Effects on Recurrence After Hepatic
      Resection of Hepatocellular Carcinoma: From In Vitro to a Clinical Study.
AB  - BACKGROUND/AIM: We investigated metformin-induced cytotoxic effects in vitro and
      assessed the chemopreventive effects of metformin in patients undergoing hepatic
      resection (HR) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This
      study consisted of laboratory and clinical studies. RESULTS: In vitro study using
      HCC cell lines revealed noticeable cytotoxic effects of metformin, that were
      largely weaker than those of sorafenib. In the clinical study, no statistical
      differences were found in tumor recurrence or overall survival between metformin
      and control groups. In contrast, there was a non-significant difference in tumor
      recurrence between metformin and propensity score-matched control groups, but
      there was a significant difference in overall patient survival. Metformin
      administration was an independent risk factor for patient survival. CONCLUSION:
      In conclusion, our in vitro laboratory study demonstrated the presence of
      cytotoxic effects of metformin. Metformin administration was associated with
      reduced tumor recurrence and helped induce significant improvements in overall
      patient survival in patients who underwent HR for HCC.

PMID- 29599369
TI  - Phase I-II Study of Short-course Accelerated Radiotherapy (SHARON) for Palliation
      in Head and Neck Cancer.
AB  - AIM: To determine the maximum tolerated dose (MTD) of a short-course accelerated
      radiotherapy and its feasibility for symptomatic palliation of advanced head and
      neck cancer or head and neck metastases from any primary site. PATIENTS AND
      METHODS: A phase I trial in four dose-escalation steps was planned: total dose
      ranged between 14 and 20 Gy in a total of four fractions administered twice a
      day. The dose-limiting toxicity (DLT) was determined as grade 3 or more toxicity
      occurring during treatment. The MTD obtained was used to plan a phase II trial.
      RESULTS: A total of 48 patients were treated. In the phase I trial, the 20 Gy
      dose level was determined to be the MTD. In the phase II trial, the palliative
      response rate was 82.7%, with a median duration of palliation of 3 months.
      CONCLUSION: Short-course accelerated radiotherapy was well tolerated and
      effective for palliation. These findings may help design future prospective
      randomized studies.

PMID- 29599370
TI  - Predictive Factors for Local Control and Survival in Patients with Cancer of
      Unknown Primary (CUP) Irradiated for Cerebral Metastases.
AB  - BACKGROUND/AIM: To identify predictors of local control and survival after whole
      brain irradiation (WBI) for cerebral metastases from cancer of unknown primary
      (CUP). PATIENTS AND METHODS: In 140 patients receiving WBI alone or following
      resection, seven factors were investigated including treatment approach, WBI
      regimen, age, gender, Eastern Cooperative Oncology Group (ECOG) performance
      score, number of cerebral lesions and extra-cerebral metastases. RESULTS: On
      univariate analysis, resection plus WBI and boost (p=0.002), ECOG 0-1 (p<0.001)
      and a single lesion (p<0.001) were positively associated with local control. On
      Cox regression, ECOG-score remained significant (p=0.002). On univariate analysis
      of survival, surgery plus WBI and boost (p=0.009), ECOG 0-1 (p<0.001), a single
      lesion (p=0.024) and no extra-cerebral metastases (p<0.001) were associated with
      better outcomes. On Cox regression, ECOG-score (p<0.001) and extra-cerebral
      lesions (p<0.001) were significant. CONCLUSION: Significant predictors of local
      control and survival were identified that contribute to treatment personalization
      and design of prospective trials in patients with cerebral metastases from CUP.

PMID- 29599371
TI  - Usefulness of TAS-102 as Third-line Chemotherapy for Metastatic Colorectal
      Cancer.
AB  - BACKGROUND/AIM: The feasibility and oncological outcomes of treatment with TAS
      102, that is recommended as third-line chemotherapy for patients with metastatic
      colorectal cancer (mCRC), remain unknown. PATIENTS AND METHODS: Between 2013 and
      2015, seven patients (five males, two females) with mCRC who were administered
      TAS-102 as third-line chemotherapy at our Institution were retrospectively
      studied. During the same period, seven patients with mCRC with Kirsten rat
      sarcoma viral oncogene homolog (KRAS) wild-type primary lesions who were
      administered irinotecan with panitumumab comprised the control group. RESULTS:
      The duration of third-line chemotherapy in the TAS-102 group was 217.0 (range=136
      337) days compared to 226.9 (range=122-335) days in the control group, with no
      significant difference in the duration of administration between the two groups.
      No significant difference in overall survival was identified between the two
      groups No serious adverse effects were encountered in either group. CONCLUSION:
      TAS-102 may be suitable as third-line chemotherapy for patients with mCRC.

PMID- 29599372
TI  - Interventions to Reduce Neurological Symptoms in Patients with GBM Receiving
      Radiotherapy: From Theory to Clinical Practice.
AB  - BACKGROUND: Patients affected by glioblastoma often develop cerebral oedema as a
      life-threatening complication. Although there is no approved pharmacological
      intervention, such cerebral oedema is usually treated with dexamethasone.
      Dexamethasone has been shown in experimental studies to reduce cerebral oedema
      with only few mineralocorticoid side-effects. The goal of our study was to
      examine its efficacy in reducing the emergence of neurological deficits during
      the Stupp protocol. PATIENTS AND METHODS: We studied a retrospective cohort of
      459 patients, assigned in controlled groups: in group A, patients received
      radiochemotherapy followed by adjuvant chemotherapy; in group B, patients
      received an equivalent combined treatment with dexamethasone. RESULTS: The
      frequency of neurological symptoms was significantly lower in dexamethasone
      treated patients. CONCLUSION: Early diagnosis and prevention of cerebral oedema
      are important because functional consequences can be anticipated with an
      appropriate medical treatment. Thus, our study reveals that dexamethasone acts to
      prevent the appearance of neurological symptoms in patients with brain tumour.

PMID- 29599373
TI  - Clinicopathological Profiling of LC3B, an Autophagy Marker, and ESRRA (Estrogen
      related Receptor-alpha) in Muscle-invasive Bladder Cancer.
AB  - BACKGROUND/AIM: Microtubule-associated protein 1 light chain 3B (LC3B), an
      autophagy marker, has been used as a promising marker in various cancer types.
      However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its
      prognostic significance have not been investigated. Recent studies pointed to the
      involvement of ESRRA in regulating autophagy via both transcriptional and post
      translational control. In the current study, prognostic importance of LC3B and
      ESRRA in MIBC was investigated. PATIENTS AND METHODS: We immunohistochemically
      studied the expression of LC3B and ESRRA in 56 MIBC samples. RESULTS: LC3B was
      stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%).
      ESRRA expression was high for 20 patients (35.7%) and low for 36 patients
      (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated
      significantly with disease-free survival rates. Double-positive LC3B and ESRRA
      correlated with poor overall survival (p=0.007) and disease-free survival
      (p=0.001) in MIBC patients. CONCLUSION: LC3B and ESRRA might be a useful
      prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA
      might be a prognostic and therapeutic target for patients with bladder cancer.

PMID- 29599374
TI  - Natural History of Squamous Intraepithelial Lesions in Pregnancy and Mode of
      Delivery.
AB  - BACKGROUND: Numerous studies have addressed the impact of mode of delivery on the
      natural history of squamous intraepithelial lesions (SIL) in pregnant women.
      However, the literature is still contradictory. PATIENTS AND METHODS: In the
      course of a retrospective analysis, data of 63 pregnant women with abnormal
      cervical smears who were referred to our Outpatient Department for pre-invasive
      lesions of the cervix were analyzed. The study was conducted at the General
      Hospital in Vienna, Austria, between 2010 and 2015. Data collection included
      demographics, delivery route and diagnostic results of cervical lesions by
      cytology, colposcopy, human papilloma virus (HPV) testing, histological report of
      punch biopsy and, if applicable, cone biopsy. RESULTS: Among 63 women who met the
      inclusion criteria, 40 (63%) delivered vaginally and 23 (37%) underwent caesarean
      section. Postpartum regression of cervical dysplasia was documented in 15 women
      delivering vaginally and in 10 who had a caesarean section (p=0.641). Among those
      women who delivered vaginally, three had progression and in 22 women the lesions
      persisted postpartum. In the group of women with caesarean section, one had
      progression and the lesions of 12 women persisted after delivery. No woman had
      progression to invasive disease. CONCLUSION: The mode of delivery does not
      significantly influence the natural history of cervical dysplastic lesions in
      pregnant women. The numbers of spontaneous regressions to normal cervical
      cytology during pregnancy were similar in both groups.

PMID- 29599375
TI  - Enterocolitis in Patients with Cancer Treated with Docetaxel.
AB  - BACKGROUND: Enterocolitis is a rare, but serious gastrointestinal complication
      associated with docetaxel-based chemotherapy in patients with cancer. The
      incidence, clinical presentation and outcome of enterocolitis in patients with
      cancer treated with docetaxel-based chemotherapy was assessed in this study
      Patients and Methods: All patients treated with docetaxel for cancer between
      January 2010 and December 2014 at the University Hospital of Besancon were
      identified and their medical records reviewed. RESULTS: During this period, 1,227
      patients received docetaxel chemotherapy and gastrointestinal events occurred in
      381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal
      events was associated with a higher dose of docetaxel (>=75 mg/m2) (odds
      ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first
      cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients
      with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile
      neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65
      (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%)
      patients, respectively; 54 patients (14.2%) were hospitalized. Computed
      tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients
      presented radiological signs of enterocolitis. Three deaths (0.8%) related to
      enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and
      the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120
      patients (31.5%). CONCLUSION: Gastrointestinal events in patients treated with
      docetaxel may be a potential sign of fatal enterocolitis and require particular
      attention. Dose reduction at the first cycle may reduce the risk of such events.

PMID- 29599376
TI  - Effectiveness and Safety of Tissue Expander for Adjuvant Helical Tomotherapy in
      Curatively Resected Retroperitoneal Sarcoma.
AB  - BACKGROUND/AIM: We investigated the effectiveness and safety of using a tissue
      expander (TE) for adjuvant helical tomotherapy (HT) for curatively resected
      retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: This study was conducted
      with 60 RPS patients who underwent curative resection with or without TE
      insertion followed by HT from June 2009 to December 2016. Among the patients, TE
      was inserted in 37 (61.7%). The quality of TE insertion was evaluated. Median
      follow-up after surgery was 19.4 months (range=4.5-93.2 months). RESULTS: A
      higher biologically-equivalent dose (alpha/beta=10) was used with patients who
      had TE insertion (median, 72.0 gray [Gy] vs. 67.1 Gy, p=0.02). The quality of TE
      insertion was excellent in 18 patients (48.6%), good in 10 (27.0%), fair in seven
      (18.9%), and poor in two (5.4%). Toxicity was not significantly different
      according to TE insertion. Local recurrence-free survival (LRFS) was 78.2%, and
      overall survival was 95.6% at 3 years. TE insertion was not a significant factor
      for LRFS (91.1% in TE vs. 62.9% in non-TE group at 3 years, p=0.62). In the
      subgroup of patients with R1 or unknown tumor margin status, however, LRFS was
      marginally higher in the TE insertion group (100.0% in TE vs. 62.9% non-TE group
      at 3 years, p=0.05). CONCLUSION: HT with TE insertion as adjuvant RT for
      curatively resected RPS was feasible with acceptable toxicity. In the patients
      with R1 or unknown tumor margin status, LRFS was marginally higher in the TE
      insertion group after HT.

PMID- 29599377
TI  - Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy
      for the Diagnosis and Treatment of Breast Disease.
AB  - BACKGROUND/AIM: To evaluate the usefulness and safety of vacuum-assisted breast
      biopsy (VABB) for breast lesion diagnosis and treatment. PATIENTS AND METHODS:
      Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB
      procedures were analyzed. RESULTS: Most patients (58.2%) were <40 years old. Most
      lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were >=3.0 cm;
      fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical
      ductal hyperplasia were underestimated. The positive predictive values (PPVs) of
      breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%,
      3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions,
      respectively. The mean number of core specimens was 9.5+/-8.8; the mean procedure
      time was 3.4+/-2.7 min. No residual lesions were found in 94.4% of the 7,480
      patients. CONCLUSION: VABB could replace ultrasound-guided core biopsy and
      surgical excisional biopsy for the diagnosis of breast disease and the treatment
      of benign breast lesions.

PMID- 29599378
TI  - Effects of supplemental oxygen therapy in patients with suspected acute
      myocardial infarction: a meta-analysis of randomised clinical trials.
AB  - BACKGROUND: Although oxygen therapy has been used for over a century in the
      management of patients with suspected acute myocardial infarction (AMI), recent
      studies have raised concerns around the efficacy and safety of supplemental
      oxygen in normoxaemic patients. OBJECTIVE: To synthesise the evidence from
      randomised controlled trials (RCTs) that investigated the effects of supplemental
      oxygen therapy compared with room air in patients with suspected or confirmed
      AMI. METHODS: For this aggregate data meta-analysis, multiple databases were
      searched from inception to 30 September 2017. RCTs with any length of follow-up
      and any outcome measure were included if they studied the use of supplemental O2
      therapy administered by any device at normal pressure compared with room air.
      Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines, an investigator assessed all the included studies and extracted the
      data. Outcomes of interests included mortality, troponin levels, infarct size,
      pain and hypoxaemia. RESULTS: Eight RCTs with a total of 7998 participants (3982
      and 4002 patients in O2 and air groups, respectively) were identified and pooled.
      In-hospital and 30-day death occurred in 135 and 149 patients, respectively.
      Oxygen therapy did not reduce the risk of in-hospital (OR, 1.11 (95% CI 0.69 to
      1.77)) or 30-day mortality (OR, 1.09 (95% CI 0.80 to 1.50)) in patients with
      suspected AMI, and the results remained similar in the subgroup of patients with
      confirmed AMI. The infarct size (based on cardiac MRI) in a subgroup of patients
      was not different between groups with and without O2 therapy. O2 therapy reduced
      the risk of hypoxaemia (OR, 0.29 (95% CI 0.17 to 0.47)). CONCLUSION: Although
      supplemental O2 therapy is commonly used, it was not associated with important
      clinical benefits. These findings from eight RCTs support departing from the
      usual practice of administering oxygen in normoxaemic patients.

PMID- 29599380
TI  - Basilic vein haemangioma: an unusual differential diagnosis for cubital fossa
      mass.
AB  - Subcutaneous masses along the cubital fossa can be a diagnostic dilemma. Most
      patients are asymptomatic and usually present for a cosmetic reason. Diagnosis
      can be confirmed by radiological findings and histopathology. We present a case
      report of a similar mass that turned out to be a haemangioma arising from the
      basilic vein with brief review of literature.

PMID- 29599379
TI  - Comparison of general anaesthesia and non-general anaesthesia approach in
      transfemoral transcatheter aortic valve implantation.
AB  - OBJECTIVE: Performing transfemoral transcatheter aortic valve implantation (TAVI)
      without general anaesthesia (GA) has been increasingly adopted. We sought to
      study the impact of GA and non-GA approaches on procedural outcome and 30-day and
      1-year mortality in transfemoral TAVI. METHODS: The UK TAVI registry holds
      information for every TAVI procedure in the UK. We analysed the data for patients
      implanted during 2013-2014 using either an Edwards Sapien or a Medtronic
      CoreValve prosthesis. Propensity score-matching analysis was performed to adjust
      for confounding factors. RESULTS: 2243 patients were studied (aged 81.4+/-7.5
      years, 1195 males). 1816 (81%) underwent TAVI with GA and 427 (19%) without GA.
      Transoesophageal echocardiography (TOE) was used in 92.3% of GA and 12.4% of non
      GA cases (p<0.001). There was no significant difference in the rate of successful
      valve deployment (GA 97.2% vs non-GA 95.7%, p=0.104) and in the incidence of more
      than mild aortic regurgitation (AR) at the end of the procedure (GA 5.6% vs non
      GA 7.0%, p=0.295). However, procedure time was longer (131+/-60 vs 121+/-60mins,
      p=0.002) and length of stay was greater (8.0+/-13.5 vs 5.7+/-5.5 days, p<0.001)
      for GA cases. 30-day and 1-year mortality rates did not differ between the GA and
      non-GA cases. After propensity matching, these results remained unchanged. A
      second propensity analysis (adjusted for mode of anaesthesia) did not show an
      association between use of TOE and rate of successful valve deployment or
      frequency of significant AR. Neither was TOE associated with a longer procedural
      time or greater length of stay. CONCLUSION: Procedure outcome, and 30-day and 1
      year mortality are not influenced by mode of anaesthesia. However, GA is
      associated with longer procedure duration and greater length of stay.

PMID- 29599381
TI  - Secondary mania following cancer chemotherapy with capecitabine.
AB  - Mania-like states occurring due to neurological, metabolic or toxic conditions,
      without a primary mood disorder have been reported in scientific literature as
      secondary mania. A major clinical problem in such situations often stems from the
      difficulty to understand if the mood disturbance is indeed secondary to an
      organic cause or a coincidental primary mood disorder. Chemotherapy regimens have
      been associated with multiple psychiatric complications, including psychosis,
      mania and anxiety. Capecitabine is implicated to be associated with
      encephalopathy whose clinical presentation often mimics that of psychosis.
      However, presentations with mania have not been reported until with the
      capecitabine and oxaliplatin combination chemotherapy regimen. In this report, we
      describe a case of secondary mania in a patient suffering from carcinoma colon on
      treatment with chemotherapy regimen of capecitabine and oxaliplatin.

PMID- 29599382
TI  - Large intra-abdominal seminoma in a left undescended testicle complicated by
      torsion.
AB  - A 39-year-old man presented with a 2-day history of worsening constant, dull
      diffuse lower abdominal pain with associated constipation and known history of
      left undescended testicle. He was evaluated at an outside hospital where a non
      contrasted CT scan revealed a 20 cm well-circumscribed soft tissue mass within
      the pelvis.He was referred and further imaging revealed a 12 cm heterogeneous
      mass with foci of air that appeared to be contiguous with the left spermatic
      cord. This constellation of findings could represent torsion of undescended left
      testicle with infarction or underlying malignancy. Tumour markers were only
      significant for elevated lactate dehydrogenase of 1445. A subsequent ultrasound
      guided biopsy of the mass demonstrated seminoma.Surgical resection revealed a
      large intra-abdominal mass emanating from the left spermatic cord with 270
      degrees  of torsion. There appeared to be a left atrophic remnant testicle at the
      base of the mass with final pathology confirming the diagnosis of classic
      seminoma.

PMID- 29599383
TI  - Ethics of a therapeutic trial: addressing limitations of an active intervention
      in optic nerve lymphoma.
AB  - We report a unique case of optic nerve lymphoma after completion of chemotherapy
      for non-Hodgkin's lymphoma. The uncommon nature of presentation, our therapeutic
      dilemma and the further course of treatment are reported. In cases with extremely
      poor prognosis, unnecessary treatment puts additional strain both financially and
      psychologically on the patients and their family. Therapeutic focus should be on
      hospice care and family counselling. The decision to not treat is a crucial
      component of cancer management; however, the ethics of this decision are yet to
      be suitably addressed by the literature.

PMID- 29599384
TI  - Pneumatosis intestinalis in a preterm infant: should we treat all intestinal
      pneumatosis as necrotising enterocolitis?
AB  - Gastric pneumatosisis a very rare site of pneumatosis intestinalis (PI), and we
      report this finding in a preterm female infant with cyanotic congenital heart
      disease. The infant was stable initially on nasal intermittent mandatory
      ventilation; however, torrential pulmonary flow through a large patent ductus
      arteriosus prompted closure using oral ibuprofen. After an episode of
      haematochezia, she developed PI, affecting mainly the gastric wall and small
      intestine with portal venous gas. Her bowel movements were regular, with no
      abdominal distension or significant gastric aspirates. She was haemodynamically
      stable with negative infective markers. Management consisted of endotracheal
      intubation and ventilation, gastric decompression and broad-spectrum antibiotics.
      Both the gastric and intestinal pneumatosis resolved within 24 hours and she made
      an uneventful recovery. If PI is not due to necrotising enterocolitis, enteral
      nutrition can be initiated early and prolonged course of broad-spectrum
      antibiotics could have been avoided.

PMID- 29599385
TI  - Prevalence and sociodemographic determinants of adult obesity: a large
      representative household survey in a resource-constrained African setting with
      double burden of undernutrition and overnutrition.
AB  - BACKGROUND: The obesity epidemic has continued to spread across the globe
      involving even poor nations of the world. METHOD: Household population survey of
      adults aged 20-60 years. Multistage stratified cluster randomised sampling
      involving both urban and rural statewide representative population samples.
      Anthropometric measurements were taken using standard methods. Prevalences were
      weighted and multinomial regression analyses were done. RESULTS: A total of 6628
      individuals from 2843 households were surveyed. The weighted overall prevalence
      for underweight was 9.1% (95% CI 8.1 to 10.1), 65.1% (95% CI 63.6 to 66.6) for
      normal weight, 19.0% (95% CI 17.8 to 20.3) for overweight and 6.8% (95% CI 6.0 to
      7.5) for obese. Men were less likely to be overweight (adjusted OR (AOR) 0.79;
      95% CI 0.68 to 0.92) and obese (AOR 0.24; 95% CI 0.19 to 0.31) than women. Urban
      residents were more likely to be overweight (AOR 1.42; 95% CI 1.18 to 1.71) and
      obese (AOR 2.09; 95% CI 1.58 to 2.76) than rural residents. Each additional 1
      year increase in age increased the risk of overweight by 1.012 (AOR 1.012; 95% CI
      1.005 to 1.018) and that of obesity by 1.03 (AOR 1.03; 95% CI 1.02 to 1.04). The
      low-income class was less likely to be overweight (AOR 0.694; 95% CI 0.507 to
      0.951) and obese (AOR 0.44; 95% CI 0.28 to 0.67). CONCLUSION: The prevalence of
      obesity and overweight in Enugu Nigeria is high and fast approaching that of
      underweight. Women, urban dwellers, older adults and high-income earners are at
      higher risk for obesity and overweight. The study provides robust information for
      public health policies towards the prevention of obesity in Nigeria.

PMID- 29599386
TI  - Association between psychological distress and mortality: the case of Israel.
AB  - BACKGROUND: Previous studies have demonstrated the association between
      psychological distress (measured by the 12-item General Health Questionnaire, GHQ
      12) and risks of all-cause mortality and deaths from cardiovascular, cancer and
      other causes. We hypothesised that in the Israeli population permanently exposed
      to war/terror stressors, this relationship is absent. METHODS: We performed an
      analysis of data from participants in the Israel National Health Survey conducted
      in 2003-2004, who died during the follow-up decade. Subjects were assigned to
      groups based on GHQ-12 score: 0-10 (asymptomatic), 11-14 (subclinically
      symptomatic), 15-19 (symptomatic) and 20-36 (highly symptomatic). Data were
      weighted to the total population. RESULTS: We analysed data from 4843
      individuals, median age 40.5 (IQR 28-54); 473 participants died during the follow
      up. We found a significant increase in total mortality, cardiovascular and other
      causes of mortality (but not cancer deaths) with increase in GHQ-12 score (P for
      linear trend of ungrouped GHQ scores <0.0001, 0.0015 and <0.0001, respectively).
      The age-sex-adjusted HR for the highest GHQ-12 compared with the lowest
      asymptomatic category was 2.1 (95% CI 1.6 to 2.7) for all-cause deaths, 2.3 (95%
      CI 1.3 to 4.1) for cardiovascular disease deaths and 2.7 (95% CI 1.9 to 3.9) for
      other deaths. The HR remained significant after adjustment for education,
      smoking, alcohol consumption and diabetes. The HR even increased after excluding
      participants with baseline cardiovascular diseases and cancer. CONCLUSION:
      Contrary to our hypothesis, psychological distress was associated with all-cause
      and cardiovascular but not cancer mortality. The absence of reverse causality
      provides evidence for the direct deleterious effects of psychological distress on
      mortality outcomes.

PMID- 29599387
TI  - Clinical and sexual risk correlates of Mycoplasma genitalium in urban pregnant
      and non-pregnant young women: cross-sectional outcomes using the baseline data
      from the Women's BioHealth Study.
AB  - OBJECTIVE: Research exploring the clinical and sexual risk correlates is
      essential to define universal standards for screening and management for
      Mycoplasma genitalium (MG). The objective of this study is to determine the
      baseline prevalence of MG and associated clinical risks using cross-sectional
      data. METHODS: Adolescent and young adult women 13-29 years were recruited during
      clinical visits during which biological specimens were collected for
      Neisseriagonorrhoeae (NG) and Chlamydia trachomatis (CT) testing to provide
      vaginal specimens for MG and Trichomonasvaginalis (TV) testing. Demographic,
      clinical and sexual risk data were collected after obtaining written consent. MG
      was tested using the Hologic Gen-Probe transcription-mediated amplification-MG
      analyte-specific reagent assay and TV by the Aptima TV assay. Bivariate analyses
      were used to evaluate differences in MG prevalence based on pregnancy status,
      demographic factors, clinical symptoms, concurrent STI and sexual risk behaviour
      quiz score (maximum score=10). RESULTS: 483 patients with a mean age of 22.4
      years (SD 3.6) were enrolled. Most participants were not pregnant (66%) and
      asymptomatic (59%). MG was the most common STI (MG 16%, TV 9%, CT 8%, NG 1%).
      Neither pregnancy nor symptoms were predictive of STI positivity. Thirty-five
      percent of non-pregnant and 45% of pregnant adolescents <=19 years were positive
      for any STI. Participants with MG were 3.4 times more likely to be co-infected
      with other STIs compared with those with other STIs (OR 3.4, 95% CI 1.17 to 10.3,
      P=0.021). Mean risk quiz scores for STI positive women were six points higher
      than those who were STI negative (beta=0.63, 95% CI 0.36 to 0.90, P<0.001). There
      were no differences in risk scores for MG-positive participants compared with
      other STI positivity. CONCLUSION: MG infection was common, associated with STI co
      infection and often asymptomatic, and pregnancy status did not confer protection.

PMID- 29599388
TI  - Correction for Toyofuku et al., "Leucine-Rich Repeat Kinase 1 Regulates Autophagy
      through Turning On TBC1D2-Dependent Rab7 Inactivation".

PMID- 29599389
TI  - Dual Coding of Frequency Modulation in the Ventral Cochlear Nucleus.
AB  - Frequency modulation (FM) is a common acoustic feature of natural sounds and is
      known to play a role in robust sound source recognition. Auditory neurons show
      precise stimulus-synchronized discharge patterns that may be used for the
      representation of low-rate FM. However, it remains unclear whether this
      representation is based on synchronization to slow temporal envelope (ENV) cues
      resulting from cochlear filtering or phase locking to faster temporal fine
      structure (TFS) cues. To investigate the plausibility of those encoding schemes,
      single units of the ventral cochlear nucleus of guinea pigs of either sex were
      recorded in response to sine FM tones centered at the unit's best frequency (BF).
      The results show that, in contrast to high-BF units, for modulation depths within
      the receptive field, low-BF units (<4 kHz) demonstrate good phase locking to TFS.
      For modulation depths extending beyond the receptive field, the discharge
      patterns follow the ENV and fluctuate at the modulation rate. The receptive field
      proved to be a good predictor of the ENV responses for most primary-like and
      chopper units. The current in vivo data also reveal a high level of diversity in
      responses across unit types. TFS cues are mainly conveyed by low-frequency and
      primary-like units and ENV cues by chopper and onset units. The diversity of
      responses exhibited by cochlear nucleus neurons provides a neural basis for a
      dual-coding scheme of FM in the brainstem based on both ENV and TFS
      cues.SIGNIFICANCE STATEMENT Natural sounds, including speech, convey informative
      temporal modulations in frequency. Understanding how the auditory system
      represents those frequency modulations (FM) has important implications as robust
      sound source recognition depends crucially on the reception of low-rate FM cues.
      Here, we recorded 115 single-unit responses from the ventral cochlear nucleus in
      response to FM and provide the first physiological evidence of a dual-coding
      mechanism of FM via synchronization to temporal envelope cues and phase locking
      to temporal fine structure cues. We also demonstrate a diversity of neural
      responses with different coding specializations. These results support the dual
      coding scheme proposed by psychophysicists to account for FM sensitivity in
      humans and provide new insights on how this might be implemented in the early
      stages of the auditory pathway.

PMID- 29599390
TI  - Use of neuropsychological tests for the diagnosis of dementia: a survey of
      Italian memory clinics.
AB  - AIM: Providing an overview of the neuropsychological tests used in Italian memory
      clinics (defined as Centers for Cognitive Disorders and Dementias-CCDD in Italy)
      for the diagnosis of cognitive disorders and dementias. METHODS: A total of 501
      CCDD, out of all 536 active CCDD, were surveyed between February 2014 and August
      2015 to verify the characteristics of the centres who performed a comprehensive
      neuropsychological assessment (NPA), defined as the administration of at least
      one test for verbal and visual episodic memory, attention, constructional praxis,
      verbal fluency and executive functions (minimum core tests-MCTs), as part of the
      diagnostic process. RESULTS: A total of 45.7% of Italian CCDD performed a
      comprehensive MCT as part of the diagnostic process. The logistic regression
      model showed that the probability of including at least one psychologist in the
      team was higher in the CCDD that reported using a comprehensive NPA (OR 4.55; 95%
      CI 2.92 to 7.1), that CCDD in Southern Italy had a lower probability of using an
      MCT (OR 0.56; 95% CI 0.35 to 0.89) and that the use of an MCT was higher in
      university/Institute for Scientific Research and Healthcare CCDD (OR 10.97; 95%
      CI 3.85 to 31.25). CONCLUSION: Almost half of the CCDD administered a set of
      MCTs; while the remaining centres only performed few tests or screening
      procedures. The neuropsychological tests used in Italian CCDD were comparable
      with those used in other European countries. Performing a comprehensive NPA
      remains the best way to assess and monitor cognitive deficits over time, thus
      further debate on the current status of NPAs in clinical practice is needed.

PMID- 29599391
TI  - DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective,
      randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1,
      multicentre trial comparing the effectiveness and cost of collagenase clostridium
      histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short
      term and long-term treatment strategies in Dupuytren's contracture.
AB  - INTRODUCTION: Dupuytren's contracture (DC) is a chronic fibroproliferative
      disorder of the palmar fascia which leads to flexion contracture in one or more
      fingers. There is no definitive cure for DC, and treatment aims at relieving
      symptoms by releasing the contracture using percutaneous or operative techniques.
      METHODS AND ANALYSIS: We planned a prospective, randomised, controlled, outcome
      assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the
      effectiveness and cost of (1) collagenase clostridium histolyticum injection
      followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle
      fasciotomy followed by limited fasciectomy in non-responsive cases and (3)
      primary limited fasciectomy during short-term and long-term follow-up for Tubiana
      I-III stages DC. We will recruit participants from seven national centres in
      Finland. Primary outcome is the rate of success in the treatment arm at 5 years
      after recruitment. Success is a composite outcome comprising (1) at least 50%
      contracture release from the date of recruitment and (2) participants in a
      patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of
      contracture, (2) quick disabilities of the arm, a shoulder and hand outcome
      measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major
      adverse events, (6) patient's trust of the treatment, (7) global rating, (8) rate
      of PASS, (9) rate of minimal clinically important improvement, (10) expenses,
      (11) progression of disease, (12) progression-free survival, (13) favoured
      treatment modality, (14) patients achieving full contracture release and >50%
      improvement and (15) patient satisfaction with the treatment effect. Predictive
      factors for achieving the PASS will also be analysed. ETHICS AND DISSEMINATION:
      The protocol was approved by the Tampere University Hospital Institutional Review
      Board and Finnish Medicine Agency. The study will be performed according to the
      principles of good clinical practice. The results of the trial will be
      disseminated as published articles in peer-reviewed journals. TRIAL REGISTRATION
      NUMBER: NCT03192020; Pre-results.

PMID- 29599392
TI  - Prevalence and distribution of hypertension and related risk factors in Jilin
      Province, China 2015: a cross-sectional study.
AB  - OBJECTIVE: This study aimed to investigate the prevalence and distribution of
      hypertension and its related factors in Jilin province, China. DESIGN: A cross
      sectional study in four cities and four rural counties in Jilin as part of a
      national Chinese study. PARTICIPANTS AND SETTING: A total of 15 206 participants
      who were >=15 years old and were selected using a stratified multistage random
      sampling method. MAIN OUTCOME MEASURES: The prevalence of hypertension. RESULTS:
      The prevalence of hypertension in Jilin province was 24.7%. Moreover, the
      prevalence of hypertension increased with age in both sexes, and was higher in
      men than in women. The modifiable factors that were associated with hypertension
      were body mass index, smoking and alcohol drinking. The risk factors identified
      are similar to those in southern China, except smoking, which has no association
      with hypertension prevalence in the South. CONCLUSIONS: Age, sex, body mass
      index, smoking and alcohol drinking were risk factors of hypertension. Control of
      these related risk factors, especially smoking, may be helpful in the treatment
      and management of hypertension in Jilin province.

PMID- 29599393
TI  - Prevalence of stroke, risk factors, disability and care needs in older adults in
      Singapore: results from the WiSE study.
AB  - OBJECTIVES: The aims of the present study were to establish the prevalence of
      stroke, and to explore the association between stroke prevalence and
      sociodemographic and health factors, disability, cognitive functioning and care
      needs among older adult residents in Singapore. SETTING: Data were drawn from the
      Well-being of the Singapore Elderly study-a cross-sectional epidemiological
      survey conducted from 2012 to 2013 on older adults living in Singapore.
      PARTICIPANTS: Participants were Singapore residents (citizens and permanent
      residents) 60 years and above who were living in Singapore during the survey
      period . Older adult residents who were institutionalised were also included in
      this study. Those who were not living in Singapore or who were not contactable
      were excluded from the study. The response rate was 65.6 % (2565/3913). A total
      population sample of 2562 participants completed the survey. Participants
      comprised 43.6% males and 56.4% females. The sample comprised 39.4% Chinese,
      29.1% Malay, 30.1% Indian and 1.4% other ethnicities . PRIMARY AND SECONDARY
      OUTCOME MEASURES: History of stroke, along with other health and mental health
      conditions, disability and cognitive functioning, were determined by self-report.
      RESULTS: Weighted stroke prevalence was 7.6% among older adults aged 60 and
      above. At a multivariate level, Malay ethnicity (OR 0.41, p=0.012, 95% CI 0.20 to
      0.82), hypertension (OR 4.58, p=0.001, 95% CI 1.84 to 11.40), heart trouble (OR
      2.45, p=0.006, 95% CI 1.30 to 4.63), diabetes (OR 2.60, p=0.001, 95% CI 1.49 to
      4.53) and dementia (OR 3.57, p=0.002, 95% CI 1.57 to 8.12) were associated with
      stroke prevalence. CONCLUSIONS: Several findings of this study were consistent
      with previous reports. Given that Singapore's population is ageing rapidly, our
      findings may indicate the need to review existing support services for stroke
      survivors and their caregivers. Future research could investigate the association
      between various sociodemographic and health conditions and stroke prevalence to
      confirm some of the findings of this study.

PMID- 29599394
TI  - Improving quality and safety in nursing homes and home care: the study protocol
      of a mixed-methods research design to implement a leadership intervention.
AB  - INTRODUCTION: Nursing homes and home care face challenges across different
      countries as people are living longer, often with chronic conditions. There is a
      lack of knowledge regarding implementation and impact of quality and safety
      interventions as most research evidence so far is generated in hospitals.
      Additionally, there is a lack of effective leadership tools for quality and
      safety improvement work in this context. METHODS AND ANALYSIS: The aim of the
      'Improving Quality and Safety in Primary Care-Implementing a Leadership
      Intervention in Nursing Homes and Homecare' (SAFE-LEAD) study is to develop and
      evaluate a research-based leadership guide for managers to increase quality and
      safety competence. The project applies a mixed-methods design and explores the
      implications of the leadership guide on managers' and staffs' knowledge,
      attitudes and practices. Four nursing homes and four home care services from
      different Norwegian municipalities will participate in the intervention. Surveys,
      process evaluation (interviews, observations) and document analyses will be
      conducted to evaluate the implementation and impact of the leadership
      intervention. A comparative study of Norway and the Netherlands will establish
      knowledge of the context dependency of the intervention. ETHICS AND
      DISSEMINATION: The study is approved by the Norwegian Centre for Research Data
      (2017/52324 and 54855). The results will be disseminated through scientific
      articles, two PhD dissertations, an anthology, presentations at national and
      international conferences, and in social media, newsletters and in the press. The
      results will generate knowledge to inform leadership practices in nursing homes
      and home care. Moreover, the study will build new theory on leadership
      interventions and the role of contextual factors in nursing homes and home care.

PMID- 29599397
TI  - Pharmacology, Part 1: Introduction to Pharmacology and Pharmacodynamics.
AB  - There is an emerging need for greater understanding of pharmacology principles
      among technical staff. Indeed, the responsibility of dose preparation and
      administration, under any level of supervision, demands a foundational
      understanding of pharmacology. This is true for radiopharmaceuticals, contrast
      media, and pharmaceutical interventions or adjunctive medications. Regulation
      around the same might suggest a need to embed pharmacology theory in
      undergraduate education programs, and there is a need to disseminate that same
      foundational understanding to practicing clinicians. Moreover, pharmacology
      foundations can provide a key understanding of the principles that underpin
      quantitative techniques (e.g., pharmacokinetics). This article is the first in a
      series that aims to enhance the understanding of pharmacologic principles
      relevant to nuclear medicine. This article will deal with the introductory
      concepts, terminology, and principles that underpin the concepts to be discussed
      in the remainder of the series. The second article will build on the
      pharmacodynamic principles examined in this article with a treatment of
      pharmacokinetics. Article 3 will outline pharmacology relevant to pharmaceutical
      interventions and adjunctive medications used in general nuclear medicine,
      article 4 will cover pharmacology relevant to pharmaceutical interventions and
      adjunctive medications used in nuclear cardiology, and article 5 will discuss the
      pharmacology related to contrast media associated with CT and MRI. The final
      article (6) in the series will examine the pharmacology of drugs associated with
      the crash cart/emergency trolley.

PMID- 29599396
TI  - Diagnostic concordance of reporting lymphovascular invasion in breast cancer.
AB  - AIMS: This study aims to assess the diagnostic agreement of lymphovascular
      invasion (LVI) in invasive breast cancer (BC). METHODS: Data on LVI were
      collected from the UK National Health Service Breast Screening Programme
      pathology external quality assurance scheme database. 101 BCs assessed over a 10
      year period (2004-2014) were included. Cases were scored by an average of 600
      pathologists. Three H&E stained slides from each case were reviewed by three
      pathologists and additional variables were evaluated. RESULTS: In the whole
      series, the overall kappa value was 0.4 (range 0.26-0.53). On review, LVI was
      detected in all three slides in 20 cases (20%), in two slides in 12 cases and in
      one of the three slides in 9 cases and was not seen in 60 cases. For concordance
      analysis, the first and last groups were used to represent cases with definite
      (LVI+) and absent LVI (LVI-), respectively. In the LVI+group (n=20), the level of
      agreement ranged from 0.54 to 0.99 (median 0.86). In the LVI- group (n=60), the
      level of agreement ranged from 0.52 to 1.00 (median 0.93), with 44% of cases
      showing interobserver concordance of >95%. There was a correlation between
      increasing number of involved lymphovascular spaces in the section and higher LVI
      reporting concordance. Some degree of retraction/fixation artefacts was observed
      in 35% of cases; this was associated with a lower concordance rate. CONCLUSIONS:
      The concordance of reporting LVI is variable. Cases without LVI and those with
      multiple involved vessels are likely to have the highest concordance and the
      highest detection rates.

PMID- 29599395
TI  - Exploring factors impacting early childhood health among Aboriginal and Torres
      Strait Islander families and communities: protocol for a population-based cohort
      study using data linkage (the 'Defying the Odds' study).
AB  - INTRODUCTION: Empirical evidence on family and community risk and protective
      factors influencing the comparatively high rates of potentially preventable
      hospitalisations and deaths among Aboriginal and Torres Strait Islander infants
      and children is limited. As is evidence on geographical variation in these risks.
      The 'Defying the Odds' study aims to explore the impact of perinatal outcomes,
      maternal social and health outcomes and level of culturally secure service
      availability on the health outcomes of Western Australian (WA) Aboriginal infants
      and children aged 0-5 years. METHODS AND ANALYSIS: The study combines a
      retrospective cohort study that uses state-wide linked health and administrative
      data from 12 data sources for multiple generations within Aboriginal families in
      WA, with specifically collected survey data from health and social services
      supporting Aboriginal families in regions of WA. Data sources include
      perinatal/birth registration, hospital, emergency department, mental health
      services, drug and alcohol service use, mortality, infectious disease
      notifications, and child protection and family services. Multilevel regression
      models will be used to examine the intensity of admissions and presentations,
      mortality, intensity of long stays and morbidity-free survival (no admissions)
      for Aboriginal children born in WA in 2000-2013. Relationships between maternal
      (and grand-maternal) health and social factors and child health outcomes will be
      quantified. Community-level variation in outcomes for Aboriginal children and
      factors contributing to this variation will be examined, including the
      availability of culturally secure services. Online surveys were sent to staff
      members at relevant services to explore the scope, reach and cultural security of
      services available to support Aboriginal families across selected regions of WA.
      ETHICS AND DISSEMINATION: Ethics approvals have been granted for the study.
      Interpretation and dissemination are guided by the study team's Aboriginal
      leadership and reference groups. Dissemination will be through direct feedback
      and reports to health services in the study and via scientific publications and
      policy recommendations.

PMID- 29599398
TI  - Role of an Intensity-Transformation Function in Enhancement of Bone Scintigraphy
      Images.
AB  - Bone scintigraphy images might exceed the dynamic range (the ratio between the
      highest and the lowest displayable brightness) of the monitor. In such a case, a
      high-intensity area accompanied by loss of detail in other structures in the
      displayed image make the clinical interpretation challenging. We have
      investigated the role of an intensity-transformation (IT) function in enhancement
      of these types of images. Methods: Forty high-dynamic-range bone scintigraphy
      images were processed using an IT function. The IT function has 2 parameters:
      threshold and slope. With the threshold kept equal to the mean count of the
      image, the slope was varied from 1 to 20. A software program developed in-house
      was used to process the images. Twenty output images corresponding to one input
      image were visually inspected by 2 experienced nuclear medicine physicians to
      select images of diagnostic quality, and from their selection was determined the
      standardized slope that produced the maximum number of diagnostic images. The 2
      physicians also scored the quality of the input and output images (at the
      standardized slope) on a scale of 1-5. The Student t test was used to determine
      the significance of differences in mean score between the input and output images
      at an alpha significance level of 0.05. Results: Application of the IT function
      with standardized parameters significantly improved the quality of high-dynamic
      range bone scintigraphy images (P < 0.001, with alpha = 0.05). A slope of 8
      maximized the number of diagnostic images. Conclusion: The IT function has a
      significant role in enhancing high-dynamic-range bone scintigraphy images.

PMID- 29599399
TI  - Molecular Breast Imaging: Administered Activity Does Not Require Adjustment Based
      on Patient Size.
AB  - At our institution, molecular breast imaging (MBI) is performed with 300 MBq of
      99mTc-sestamibi for all patients. For some nuclear medicine procedures,
      administered activity or imaging time is increased for patients of larger size to
      obtain adequate counts. Our objective was to assess whether uptake of 99mTc
      sestamibi in the breast is influenced by patient size. Methods: Records from
      patients who underwent a clinical MBI examination between July and November 2016
      were reviewed. Those in whom our standard injection and preparation techniques
      were followed were included in the analysis. Patients were injected with
      approximately 300 MBq of 99mTc-sestamibi. Residual activity was measured to allow
      calculation of exact administered activity for each patient. Breast images were
      acquired at 10 min/view using a dual-head cadmium zinc telluride-based gamma
      camera. Breast thickness was measured as the distance between the 2 detectors.
      Patient height, weight, body surface area, and body mass index were obtained from
      records. Lean body mass with the James equation (LBMJames) and Janmahasatian
      correction (LBMJanma) was calculated. Count density in the breast tissue was
      measured by drawing a region of interest around the central breast tissue of the
      right breast mediolateral-oblique view of the lower detector. Count density was
      expressed as cts/cm2/MBq of administered activity. Spearman correlation
      coefficient (rs) was calculated. Results: A total of 200 patients were analyzed.
      No dose infiltration was suspected at any injection. Average administered
      activity was 292 MBq (SD, 13.8 MBq; range, 247-326 MBq). Average count density
      was 7.2 cts/cm2/MBq (SD, 2.7 cts/cm2/MBq; range, 3.1-17.8 cts/cm2/MBq). MBI count
      density was weakly negatively correlated with height (rs = -0.18; P = 0.01),
      weight (rs = -0.23; p = <0.001), body mass index (rs = -0.16; P = 0.02), body
      surface area (rs = -0.22; P = 0.002), LBMJames (rs = -0.23; P = 0.001), and
      LBMJanma (rs = -0.23; P = 0.001). No correlation was observed between count
      density and breast thickness (rs = 0.06; P = 0.37). Conclusion: Our results
      suggest a lack of relationship between uptake of 99mTc-sestamibi in breast tissue
      and body size or compressed breast thickness. Altering from the standard 300 MBq
      of administered activity for larger patients is likely unnecessary.

PMID- 29599400
TI  - Can 68Ga-DOTA Peptides Be Potential Radiotracers for PET Imaging of the Spleen?
AB  - On radionuclide somatostatin receptor imaging studies, the spleen shows high
      physiologic uptake. Reducing the intensity of the image settings helps to better
      assess the distribution of radiotracer in the spleen. In our routine studies, we
      incidentally recognized that 68Ga-DOTANOC PET provides higher-resolution splenic
      images than 111In-octreotide SPECT. Autoradiography and immunohistochemistry
      studies have shown that somatostatin receptors are located mainly in the red pulp
      of the spleen. The distribution of 68Ga-DOTANOC in the spleen appears to
      correlate with the distribution of red pulp. In this article, we present 68Ga
      DOTANOC PET/CT spleen images of our patients.

PMID- 29599401
TI  - The Effect of New Formulas for Lean Body Mass on Lean-Body-Mass-Normalized SUV in
      Oncologic 18F-FDG PET/CT.
AB  - Because of better precision and intercompatibility, the use of lean body mass
      (LBM) as a mass estimate in the calculation of SUV (SUL) has become more common
      in research and clinical studies today. Thus, the equations deciding this
      quantity must be those that best represent the actual body composition. Methods:
      LBM was calculated for 44 patients examined with 18F-FDG PET/CT scans by means of
      the sex-specific predictive equations of James and Janmahasatians, and the
      results were validated using a CT-based method that makes use of the eyes-to
      thighs CT component of the PET/CT aquisition and segments the voxels according to
      Hounsfield units. Intraclass correlation coefficients and Bland-Altman plots were
      used to assess agreement between the various methods. Results: A mean difference
      of 6.3 kg (limits of agreement, -15.1 to 2.5 kg) between [Formula: see text] and
      [Formula: see text] was found. This difference was higher than the 3.8-kg
      difference observed between [Formula: see text] and [Formula: see text] (limits
      of agreement, -12.5 to 4.9 kg). In addition, [Formula: see text] had a higher
      intraclass correlation coefficient with [Formula: see text] (0.87; 95% confidence
      interval, 0.60-0.94) than with [Formula: see text] (0.77; 95% confidence
      interval, 0.11-0.91). Thus, we obtained better agreement between [Formula: see
      text] and [Formula: see text] Although there were exceptions, the overall effect
      on SUL was that [Formula: see text] was greater than [Formula: see text]
      Conclusion: We have verified the reliability of the suggested [Formula: see text]
      formulas with a CT-derived reference standard. Compared with the more traditional
      and available set of [Formula: see text] equations, the [Formula: see text]
      formulas tend to yield better agreement.

PMID- 29599402
TI  - Workshop on Instructional Skills in the Clinical Setting.
AB  - This article describes a workshop offered annually by the radiation and imaging
      programs at Bellevue College, Bellevue, WA. The workshop provides an educator
      perspective to those who teach students in the college's clinical internships. An
      outline of the workshop is given in this article, as are the reasons for its
      ongoing success.

PMID- 29599403
TI  - 18F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for
      Lung Cancer.
AB  - Our primary purpose was to determine whether increased 18F-FDG uptake in the
      thyroid gland predicts development of thyroiditis with subsequent hypothyroidism
      in patients undergoing immunotherapy with nivolumab for lung cancer. Secondarily,
      we determined whether 18F-FDG uptake in the thyroid gland correlates with number
      of administered cycles of nivolumab. Methods: Retrospective chart review over 2 y
      found 18 lung cancer patients treated with nivolumab who underwent 18F-FDG PET/CT
      before and during therapy. SUVmean, SUVmax, and total lesion glycolysis of the
      thyroid gland were measured. SUVs were also measured for the pituitary gland,
      liver, and spleen. Patients underwent monthly thyroid testing. PET/CT parameters
      were analyzed by unpaired t testing for differences between 2 groups (patients
      who developed hypothyroidism and those who did not). Correlation between
      development of thyroiditis and number of cycles of nivolumab was also tested.
      Results: Six of 18 patients developed hypothyroidism. The t test comparing the 2
      groups demonstrated significant differences in SUVmean (P = 0.04), SUVmax (P =
      0.04), and total lesion glycolysis (P = 0.02) of the thyroid gland. Two of 4
      patients who developed thyroiditis and had increased 18F-FDG uptake in the
      thyroid gland had a normal TSH level at the time of follow-up 18F-FDG PET/CT.
      Patients who developed thyroiditis with subsequent hypothyroidism stayed longer
      on therapy (10.6 cycles) than patients without thyroiditis (7.6 cycles), but the
      trend was not statistically significant. No significant difference in PET/CT
      parameters was observed for pituitary gland, liver, or spleen. Conclusion:18F-FDG
      PET/CT can predict the development of thyroiditis with subsequent hypothyroidism
      before laboratory testing. Further study is required to confirm the positive
      trend between thyroiditis and duration of therapy.

PMID- 29599404
TI  - Time-of-Flight Information Improved the Detectability of Subcentimeter Spheres
      Using a Clinical PET/CT Scanner.
AB  - Recent advancements in clinical PET/CT scanners have improved the detectability
      of small lesions. However, the ideal reconstruction parameters for detecting
      small lesions have not yet been sufficiently clarified. The purpose of this study
      was to investigate the detectability of subcentimeter spheres using a clinical
      PET/CT scanner. Methods: We used a clinical PET/CT scanner to obtain the data of
      a National Electrical Manufacturers Association body phantom consisting of 6
      small spheres (inner diameters, 4.0, 5.0, 6.2, 7.9, 10, and 37 mm) containing 18F
      solution. The background activity was 2.65 kBq/mL, and the sphere-to-background
      ratio was 8. The PET data obtained for 2 and 120 min were reconstructed using
      ordered-subsets expectation maximization (OSEM), OSEM + point-spread function
      (PSF), and OSEM + time-of-flight (TOF) with voxel sizes of 2.04 * 2.04 * 2.00 mm
      (2-mm voxels) and 4.07 * 4.07 * 3.99 mm (4-mm voxels). A gaussian filter was not
      used. The image quality was evaluated by visual assessment, as well as by
      physical assessment of the detectability index and recovery coefficients.
      Results: According to the visual assessment, the detectability of the spheres
      improved using TOF and a longer acquisition. Using the OSEM+TOF model, the
      smallest visually detected spheres were 5 mm in diameter with a 120-min
      acquisition and 6 mm in diameter with a 2-min acquisition. According to physical
      assessment, the detectability of spheres 10 mm or smaller using the OSEM+TOF
      image was superior to that using the OSEM image. In addition, the detectability
      of each hot sphere and recovery coefficient with 2-mm voxels was superior to that
      with 4-mm voxels. Although OSEM+PSF images showed less background noise,
      detectability and the recovery coefficient were not improved for spheres 8 mm or
      smaller. Conclusion: The TOF model with 2-mm voxels improved the detectability of
      subcentimeter hot spheres on a clinical PET/CT scanner.

PMID- 29599405
TI  - Transketolase Regulates the Metabolic Switch to Control Breast Cancer Cell
      Metastasis via the alpha-Ketoglutarate Signaling Pathway.
AB  - Although metabolic reprogramming is recognized as a hallmark of tumorigenesis and
      progression, little is known about metabolic enzymes and oncometabolites that
      regulate breast cancer metastasis, and very few metabolic molecules have been
      identified as potential therapeutic targets. In this study, the transketolase
      (TKT) expression correlated with tumor size in the 4T1/BALB/c syngeneic model. In
      addition, TKT expression was higher in lymph node metastases compared with
      primary tumor or normal tissues of patients, and high TKT levels were associated
      with poor survival. Depletion of TKT or addition of alpha-ketoglutarate (alphaKG)
      enhanced the levels of tumor suppressors succinate dehydrogenase and fumarate
      hydratase (FH), decreasing oncometabolites succinate and fumarate, and further
      stabilizing HIF prolyl hydroxylase 2 (PHD2) and decreasing HIF1alpha, ultimately
      suppressing breast cancer metastasis. Reduced TKT or addition of alphaKG mediated
      a dynamic switch of glucose metabolism from glycolysis to oxidative
      phosphorylation. Various combinations of the TKT inhibitor oxythiamine,
      docetaxel, and doxorubicin enhanced cell death in triple-negative breast cancer
      (TNBC) cells. Furthermore, oxythiamine treatment led to increased levels of
      alphaKG in TNBC cells. Together, our study has identified a novel TKT-mediated
      alphaKG signaling pathway that regulates breast cancer oncogenesis and can be
      exploited as a modality for improving therapy.Significance: These findings
      uncover the clinical significance of TKT in breast cancer progression and
      metastasis and demonstrate effective therapy by inhibiting TKT or by adding
      alphaKG. Cancer Res; 78(11); 2799-812. (c)2018 AACR.

PMID- 29599406
TI  - Cost the Focus of Cancer Panel Report.
AB  - The President's Cancer Panel issued recommendations aimed at promoting value,
      affordability, and innovation in cancer drugs. The recommendations include
      increasing NIH funding, encouraging the development of generic and biosimilar
      drugs, and instituting value-based pricing policies to encourage the development
      of cost-effective drugs.

PMID- 29599408
TI  - Non-parathyroid hypercalcemia associated with paraffin oil injection in 12
      younger male bodybuilders: a case series.
AB  - INTRODUCTION: Injection of paraffin oil to augment muscles size is a troubling
      phenomenon known to cause a foreign body reaction with formation of granulomas.
      In a few case reports, long-term side effects have been reported in terms of
      hypercalcemia and renal failure. METHODS: We identified a case series of 12 male
      bodybuilders presenting with non-parathyroid hypercalcemia who previously had
      injected paraffin oil to increase muscles size. RESULTS: At admission, all
      patients had moderate-to-severe hypercalcemia with suppressed PTH levels and
      impaired renal function. Calcitriol levels were within the normal range or
      slightly elevated. Follow-up measurements showed marked hypercalciuria with
      nearly normal levels of bone turnover markers. A correlation was found between
      levels of peptidyl dipeptidase and calcitriol (R = 0.812, P = 0.050). Treatment
      with antiresorptive agents seemed less effective than glucocorticoids, which
      resulted in a significantly lowering of ionized calcium levels and improved renal
      function, although no patients were cured by this treatment. Immunosuppression
      with azathioprine or mycophenolate may have a glucocorticoid-saving effect. One
      patient had surgery with removal of affected muscle tissue, without any apparent
      effect on plasma calcium levels. CONCLUSION: The hypercalcemia and associated
      hypercalciuria seems to be due to an intestinal hyperabsorption of calcium. It
      remains to be elucidated, whether an increased calcitriol synthesis within
      granulomas is the only (main) mechanism by which intestinal calcium absorption is
      increased. Glucocorticoids seem most appropriate as the first choice for
      treatment. Bodybuilders should be warned against use of intramuscular oil
      injections (and other substances), as this may have severe adverse health
      consequences.

PMID- 29599407
TI  - Microstructural white matter alterations and hippocampal volumes are associated
      with cognitive deficits in craniopharyngioma.
AB  - CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have
      cognitive deficits. Which neural pathways are affected is unknown. OBJECTIVE: To
      determine whether there is a relationship between microstructural white matter
      (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in
      adults with childhood-onset CP. DESIGN: A cross-sectional study with a median
      follow-up time of 22 (6-49) years after operation. SETTING: The South Medical
      Region of Sweden (2.5 million inhabitants). PARTICIPANTS: Included were 41
      patients (24 women, >=17 years) surgically treated for childhood-onset CP between
      1958-2010 and 32 controls with similar age and gender distributions. HL was found
      in 23 patients. MAIN OUTCOME MEASURES: Subjects performed cognitive tests and
      magnetic resonance imaging, and images were analyzed using DTI of uncinate
      fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal
      volumetry. RESULTS: Right uncinate fasciculus was significantly altered (P <=
      0.01). Microstructural WM alterations in left ventral cingulum were significantly
      associated with worse performance in visual episodic memory, explaining
      approximately 50% of the variation. Alterations in dorsal cingulum were
      associated with worse performance in immediate, delayed recall and recognition,
      explaining 26-38% of the variation, and with visuospatial ability and executive
      function, explaining 19-29%. Patients who had smaller hippocampal volume had
      worse general knowledge (P = 0.028), and microstructural WM alterations in
      hippocampus were associated with a decline in general knowledge and episodic
      visual memory. CONCLUSIONS: A structure to function relationship is suggested
      between microstructural WM alterations in cingulum and in hippocampus with
      cognitive deficits in CP.

PMID- 29599409
TI  - Functional Precision Medicine Identifies Novel Druggable Targets and Therapeutic
      Options in Head and Neck Cancer.
AB  - Purpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common
      cancer worldwide, with high mortality and a lack of targeted therapies. To
      identify and prioritize druggable targets, we performed genome analysis together
      with genome-scale siRNA and oncology drug profiling using low-passage tumor cells
      derived from a patient with treatment-resistant HPV-negative HNSCC.Experimental
      Design: A tumor cell culture was established and subjected to whole-exome
      sequencing, RNA sequencing, comparative genome hybridization, and high-throughput
      phenotyping with a siRNA library covering the druggable genome and an oncology
      drug library. Secondary screens of candidate target genes were performed on the
      primary tumor cells and two nontumorigenic keratinocyte cell cultures for
      validation and to assess cancer specificity. siRNA screens of the kinome on two
      isogenic pairs of p53-mutated HNSCC cell lines were used to determine
      generalizability. Clinical utility was addressed by performing drug screens on
      two additional HNSCC cell cultures derived from patients enrolled in a clinical
      trial.Results: Many of the identified copy number aberrations and somatic
      mutations in the primary tumor were typical of HPV(-) HNSCC, but none pointed to
      obvious therapeutic choices. In contrast, siRNA profiling identified 391
      candidate target genes, 35 of which were preferentially lethal to cancer cells,
      most of which were not genomically altered. Chemotherapies and targeted agents
      with strong tumor-specific activities corroborated the siRNA profiling results
      and included drugs that targeted the mitotic spindle, the proteasome, and G2-M
      kinases WEE1 and CHK1 We also show the feasibility of ex vivo drug profiling for
      patients enrolled in a clinical trial.Conclusions: High-throughput phenotyping
      with siRNA and drug libraries using patient-derived tumor cells prioritizes
      mutated driver genes and identifies novel drug targets not revealed by genomic
      profiling. Functional profiling is a promising adjunct to DNA sequencing for
      precision oncology. Clin Cancer Res; 24(12); 2828-43. (c)2018 AACR.

PMID- 29599411
TI  - CD103+ Tumor-Resident CD8+ T Cells Are Associated with Improved Survival in
      Immunotherapy-Naive Melanoma Patients and Expand Significantly During Anti-PD-1
      Treatment.
AB  - Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer
      treatment. Durable responses, however, occur in less than half of those treated,
      and efforts to improve treatment efficacy are confounded by a lack of
      understanding of the characteristics of the cells that initiate antitumor immune
      response.Patients and Methods: We performed multiparameter flow cytometry and
      quantitative multiplex immunofluorescence staining on tumor specimens from
      immunotherapy-naive melanoma patients and longitudinal biopsy specimen obtained
      from patients undergoing anti-PD-1 therapy.Results: Increased numbers of
      CD69+CD103+ tumor-resident CD8+ T cells were associated with improved melanoma
      specific survival in immunotherapy-naive melanoma patients. Local IL15 expression
      levels strongly correlated with these tumor-resident T-cell numbers. The
      expression of several immune checkpoints including PD-1 and LAG3 was highly
      enriched in this subset, and these cells significantly expanded early during anti
      PD-1 immunotherapy.Conclusions: Tumor-resident CD8+ T-cell numbers are more
      prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are
      likely to initiate response to anti-PD-1 and anti-LAG-3 treatments. We propose
      that the immune profile of these cells prior to treatment could inform strategies
      for immune checkpoint blockade. Clin Cancer Res; 24(13); 3036-45. (c)2018 AACR.

PMID- 29599410
TI  - Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic
      Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer.
AB  - Purpose: Patients with advanced non-small cell lung cancer (NSCLC) whose tumors
      harbor anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with
      ALK inhibitors (ALKi). Analysis of cell-free circulating tumor DNA (cfDNA) may
      provide a noninvasive way to identify ALK fusions and actionable resistance
      mechanisms without an invasive biopsy.Patients and Methods: The Guardant360
      (G360; Guardant Health) deidentified database of NSCLC cases was queried to
      identify 88 consecutive patients with 96 plasma-detected ALK fusions. G360 is a
      clinical cfDNA next-generation sequencing (NGS) test that detects point
      mutations, select copy number gains, fusions, insertions, and deletions in
      plasma.Results: Identified fusion partners included EML4 (85.4%), STRN (6%), and
      KCNQ, KLC1, KIF5B, PPM1B, and TGF (totaling 8.3%). Forty-two ALK-positive
      patients had no history of targeted therapy (cohort 1), with tissue ALK molecular
      testing attempted in 21 (5 negative, 5 positive, and 11 tissue insufficient).
      Follow-up of 3 of the 5 tissue-negative patients showed responses to ALKi. Thirty
      one patients were tested at known or presumed ALKi progression (cohort 2); 16
      samples (53%) contained 1 to 3 ALK resistance mutations. In 13 patients, clinical
      status was unknown (cohort 3), and no resistance mutations or bypass pathways
      were identified. In 6 patients with known EGFR-activating mutations, an ALK
      fusion was identified on progression (cohort 4; 4 STRN, 1 EML4; one both STRN and
      EML4); five harbored EGFR T790M.Conclusions: In this cohort of cfDNA-detected ALK
      fusions, we demonstrate that comprehensive cfDNA NGS provides a noninvasive means
      of detecting targetable alterations and characterizing resistance mechanisms on
      progression. Clin Cancer Res; 24(12); 2758-70. (c)2018 AACR.

PMID- 29599412
TI  - Hyperpolarized [1-13C]-Pyruvate Magnetic Resonance Spectroscopic Imaging of
      Prostate Cancer In Vivo Predicts Efficacy of Targeting the Warburg Effect.
AB  - Purpose: To evaluate the potential of hyperpolarized [1-13C]-pyruvate magnetic
      resonance spectroscopic imaging (MRSI) of prostate cancer as a predictive
      biomarker for targeting the Warburg effect.Experimental Design: Two human
      prostate cancer cell lines (DU145 and PC3) were grown as xenografts. The
      conversion of pyruvate to lactate in xenografts was measured with hyperpolarized
      [1-13C]-pyruvate MRSI after systemic delivery of [1-13C] pyruvic acid. Steady
      state metabolomic analysis of xenograft tumors was performed with mass
      spectrometry and steady-state lactate concentrations were measured with proton
      (1H) MRS. Perfusion and oxygenation of xenografts were measured with electron
      paramagnetic resonance (EPR) imaging with OX063. Tumor growth was assessed after
      lactate dehydrogenase (LDH) inhibition with FX-11 (42 MUg/mouse/day for 5 days *
      2 weekly cycles). Lactate production, pyruvate uptake, extracellular
      acidification rates, and oxygen consumption of the prostate cancer cell lines
      were analyzed in vitro LDH activity was assessed in tumor homogenates.Results:
      DU145 tumors demonstrated an enhanced conversion of pyruvate to lactate with
      hyperpolarized [1-13C]-pyruvate MRSI compared with PC3 and a corresponding
      greater sensitivity to LDH inhibition. No difference was observed between PC3 and
      DU145 xenografts in steady-state measures of pyruvate fermentation, oxygenation,
      or perfusion. The two cell lines exhibited similar sensitivity to FX-11 in vitro
      LDH activity correlated to FX-11 sensitivity.Conclusions: Hyperpolarized [1-13C]
      pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg
      effect. Clin Cancer Res; 24(13); 3137-48. (c)2018 AACR.

PMID- 29599414
TI  - Insights into calcium-sensing receptor trafficking and biased signalling by
      studies of calcium homeostasis.
AB  - The calcium-sensing receptor (CASR) is a class C G-protein-coupled receptor
      (GPCR) that detects extracellular calcium concentrations, and modulates
      parathyroid hormone secretion and urinary calcium excretion to maintain calcium
      homeostasis. The CASR utilises multiple heterotrimeric G-proteins to mediate
      signalling effects including activation of intracellular calcium release; mitogen
      activated protein kinase (MAPK) pathways; membrane ruffling; and inhibition of
      cAMP production. By studying germline mutations in the CASR and proteins within
      its signalling pathway that cause hyper- and hypocalcaemic disorders, novel
      mechanisms governing GPCR signalling and trafficking have been elucidated. This
      review focusses on two recently described pathways that provide novel insights
      into CASR signalling and trafficking mechanisms. The first, identified by
      studying a CASR gain-of-function mutation that causes autosomal dominant
      hypocalcaemia (ADH), demonstrated a structural motif located between the third
      transmembrane domain and the second extracellular loop of the CASR that mediates
      biased signalling by activating a novel beta-arrestin-mediated G-protein
      independent pathway. The second, in which the mechanism by which adaptor protein
      2 sigma-subunit (AP2sigma) mutations cause familial hypocalciuric hypercalcaemia
      (FHH) was investigated, demonstrated that AP2sigma mutations impair CASR
      internalisation and reduce multiple CASR-mediated signalling pathways.
      Furthermore, these studies showed that the CASR can signal from the cell surface
      using multiple G-protein pathways, whilst sustained signalling is mediated only
      by the Gq/11 pathway. Thus, studies of FHH- and ADH-associated mutations have
      revealed novel steps by which CASR mediates signalling and compartmental bias,
      and these pathways could provide new targets for therapies for patients with
      calcaemic disorders.

PMID- 29599413
TI  - Combinatorial Effects of VEGFR Kinase Inhibitor Axitinib and Oncolytic
      Virotherapy in Mouse and Human Glioblastoma Stem-Like Cell Models.
AB  - Purpose: Glioblastoma (GBM), a fatal brain cancer, contains a subpopulation of
      GBM stem-like cells (GSCs) that contribute to resistance to current therapy.
      Angiogenesis also plays a key role in GBM progression. Therefore, we developed a
      strategy to target the complex GBM microenvironment, including GSCs and tumor
      vasculature.Experimental Design: We evaluated the cytotoxic effects of VEFGR
      tyrosine kinase inhibitor (TKI) axitinib in vitro and then tested antitumor
      efficacy of axitinib in combination with oncolytic herpes simplex virus (oHSV)
      expressing antiangiogenic cytokine murine IL12 (G47Delta-mIL12) in two orthotopic
      GSC-derived GBM models: patient-derived recurrent MGG123 GSCs, forming vascular
      xenografts in immunodeficient mice; and mouse 005 GSCs, forming syngeneic tumors
      in immunocompetent mice.Results: GSCs form endothelial-like tubes and were
      sensitive to axitinib. G47Delta-mIL12 significantly improved survival, as did
      axitinib, while dual combinations further extended survival significantly
      compared with single therapies alone in both models. In MGG123 tumors, axitinib
      was effective only at high doses (50 mg/kg), alone and in combination with
      G47Delta-mIL12, and this was associated with greatly decreased vascularity,
      increased macrophage infiltration, extensive tumor necrosis, and PDGFR/ERK
      pathway inhibition. In the mouse 005 model, antiglioma activity, after single and
      combination therapy, was only observed in immunocompetent mice and not the T-cell
      deficient athymic mice. Interestingly, immune checkpoint inhibition did not
      improve efficacy.Conclusions: Systemic TKI (axitinib) beneficially combines with
      G47Delta-mIL12 to enhance antitumor efficacy in both immunodeficient and
      immunocompetent orthotopic GBM models. Our results support further investigation
      of TKIs in combination with oHSV for GBM treatment. Clin Cancer Res; 24(14); 3409
      22. (c)2018 AACR.

PMID- 29599415
TI  - The 'ethics committee' job is administrative: a response to commentaries.

PMID- 29599416
TI  - Low-protein diet in puberty impairs testosterone output and energy metabolism in
      male rats.
AB  - We examined the long-term effects of protein restriction during puberty on the
      function of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary
      gonadal (HPG) axes in male rats. Male Wistar rats from the age of 30 to 60 days
      were fed a low-protein diet (4%, LP). A normal-protein diet (20.5%) was
      reintroduced to rats from the age of 60 to 120 days. Control rats were fed a
      normal-protein diet throughout life (NP). Rats of 60 or 120 days old were killed.
      Food consumption, body weight, visceral fat deposits, lipid profile, glycemia,
      insulinemia, corticosteronemia, adrenocorticotropic hormone (ACTH),
      testosteronemia and leptinemia were evaluated. Glucose-insulin homeostasis,
      pancreatic-islet insulinotropic response, testosterone production and
      hypothalamic protein expression of the androgen receptor (AR), glucocorticoid
      receptor (GR) and leptin signaling pathway were also determined. LP rats were
      hypophagic, leaner, hypoglycemic, hypoinsulinemic and hypoleptinemic at the age
      of 60 days (P < 0.05). These rats exhibited hyperactivity of the HPA axis,
      hypoactivity of the HPG axis and a weak insulinotropic response (P < 0.01). LP
      rats at the age of 120 days were hyperphagic and exhibited higher visceral fat
      accumulation, hyperleptinemia and dyslipidemia; lower blood ACTH, testosterone
      and testosterone release; and reduced hypothalamic expression of AR, GR and
      SOCS3, with a higher pSTAT3/STAT3 ratio (P < 0.05). Glucose-insulin homeostasis
      was disrupted and associated with hyperglycemia, hyperinsulinemia and increased
      insulinotropic response of the pancreatic islets. The cholinergic and glucose
      pancreatic-islet responses were small in 60-day-old LP rats but increased in 120
      day-old LP rats. The hyperactivity of the HPA axis and the suppression of the HPG
      axis caused by protein restriction at puberty contributed to energy and metabolic
      disorders as long-term consequences.

PMID- 29599417
TI  - Robotics-inspired biology.
AB  - For centuries, designers and engineers have looked to biology for inspiration.
      Biologically inspired robots are just one example of the application of knowledge
      of the natural world to engineering problems. However, recent work by biologists
      and interdisciplinary teams have flipped this approach, using robots and physical
      models to set the course for experiments on biological systems and to generate
      new hypotheses for biological research. We call this approach robotics-inspired
      biology; it involves performing experiments on robotic systems aimed at the
      discovery of new biological phenomena or generation of new hypotheses about how
      organisms function that can then be tested on living organisms. This new and
      exciting direction has emerged from the extensive use of physical models by
      biologists and is already making significant advances in the areas of
      biomechanics, locomotion, neuromechanics and sensorimotor control. Here, we
      provide an introduction and overview of robotics-inspired biology, describe two
      case studies and suggest several directions for the future of this exciting new
      research area.

PMID- 29599418
TI  - New workflow for classification of genetic variants' pathogenicity applied to
      hereditary recurrent fevers by the International Study Group for Systemic
      Autoinflammatory Diseases (INSAID).
AB  - BACKGROUND: Hereditary recurrent fevers (HRFs) are rare inflammatory diseases
      sharing similar clinical symptoms and effectively treated with anti-inflammatory
      biological drugs. Accurate diagnosis of HRF relies heavily on genetic testing.
      OBJECTIVES: This study aimed to obtain an experts' consensus on the clinical
      significance of gene variants in four well-known HRF genes: MEFV, TNFRSF1A, NLRP3
      and MVK. METHODS: We configured a MOLGENIS web platform to share and analyse
      pathogenicity classifications of the variants and to manage a consensus-based
      classification process. Four experts in HRF genetics submitted independent
      classifications of 858 variants. Classifications were driven to consensus by
      recruiting four more expert opinions and by targeting discordant classifications
      in five iterative rounds. RESULTS: Consensus classification was reached for
      804/858 variants (94%). None of the unsolved variants (6%) remained with opposite
      classifications (eg, pathogenic vs benign). New mutational hotspots were found in
      all genes. We noted a lower pathogenic variant load and a higher fraction of
      variants with unknown or unsolved clinical significance in the MEFV gene.
      CONCLUSION: Applying a consensus-driven process on the pathogenicity assessment
      of experts yielded rapid classification of almost all variants of four HRF genes.
      The high-throughput database will profoundly assist clinicians and geneticists in
      the diagnosis of HRFs. The configured MOLGENIS platform and consensus evolution
      protocol are usable for assembly of other variant pathogenicity databases. The
      MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis;
      the specific HRF configuration is available at http://molgenis.org/said/. The HRF
      pathogenicity classifications will be published on the INFEVERS database at
      https://fmf.igh.cnrs.fr/ISSAID/infevers/.

PMID- 29599419
TI  - Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the
      phenotype of MAGEL2-related disorders.
AB  - BACKGROUND: Chitayat-Hall syndrome, initially described in 1990, is a rare
      condition characterised by distal arthrogryposis, intellectual disability,
      dysmorphic features and hypopituitarism, in particular growth hormone deficiency.
      The genetic aetiology has not been identified. METHODS AND RESULTS: We identified
      three unrelated families with a total of six affected patients with the clinical
      manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome
      sequencing, pathogenic variants in the MAGEL2 gene were identified in all
      affected patients. All disease-causing sequence variants detected are predicted
      to result in a truncated protein, including one complex variant that comprised a
      deletion and inversion. CONCLUSIONS: Chitayat-Hall syndrome is caused by
      pathogenic variants in MAGEL2 and shares a common aetiology with the recently
      described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is
      expanded to include growth hormone deficiency as an important and treatable
      complication.

PMID- 29599420
TI  - Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue
      inflammation.
AB  - In mammals, white adipose tissue (WAT) stores and releases lipids, whereas brown
      adipose tissue (BAT) oxidizes lipids to fuel thermogenesis. In obese individuals,
      WAT undergoes profound changes; it expands, becomes dysfunctional, and develops a
      low-grade inflammatory state. Importantly, BAT content and activity decline in
      obese subjects, mainly as a result of the conversion of brown adipocytes to white
      like unilocular cells. Here, we show that BAT "whitening" is induced by multiple
      factors, including high ambient temperature, leptin receptor deficiency, beta
      adrenergic signaling impairment, and lipase deficiency, each of which is capable
      of inducing macrophage infiltration, brown adipocyte death, and crown-like
      structure (CLS) formation. Brown-to-white conversion and increased CLS formation
      were most marked in BAT from adipose triglyceride lipase (Atgl)-deficient mice,
      where, according to transmission electron microscopy, whitened brown adipocytes
      contained enlarged endoplasmic reticulum, cholesterol crystals, and some
      degenerating mitochondria, and were surrounded by an increased number of collagen
      fibrils. Gene expression analysis showed that BAT whitening in Atgl-deficient
      mice was associated to a strong inflammatory response and NLRP3 inflammasome
      activation. Altogether, the present findings suggest that converted enlarged
      brown adipocytes are highly prone to death, which, by promoting inflammation in
      whitened BAT, may contribute to the typical inflammatory state seen in obesity.

PMID- 29599421
TI  - Learning through a virtual patient vs. recorded lecture: a comparison of
      knowledge retention in a trauma case.
AB  - Objectives: To compare medical students' and residents' knowledge retention of
      assessment, diagnosis and treatment procedures, as well as a learning experience,
      of patients with spinal trauma after training with either a Virtual Patient case
      or a video-recorded traditional lecture. Methods: A total of 170 volunteers (85
      medical students and 85 residents in orthopedic surgery) were randomly allocated
      (stratified for student/resident and gender) to either a video-recorded standard
      lecture or a Virtual Patient-based training session where they interactively
      assessed a clinical case portraying a motorcycle accident. The knowledge
      retention was assessed by a test immediately following the educational
      intervention and repeated after a minimum of 2 months. Participants' learning
      experiences were evaluated with exit questionnaires. A repeated-measures analysis
      of variance was applied on knowledge scores. A total of 81% (n = 138) of the
      participants completed both tests. Results: There was a small but significant
      decline in first and second test results for both groups (F(1, 135) = 18.154, p =
      0.00). However, no significant differences in short-term and long-term knowledge
      retention were observed between the two teaching methods. The Virtual Patient
      group reported higher learning experience levels in engagement, stimulation,
      general perception, and expectations. Conclusions: Participants' levels
      engagement were reported in favor of the VP format. Similar knowledge retention
      was achieved through either a Virtual Patient or a recorded lecture.

PMID- 29599422
TI  - Fatal Acute Respiratory Distress Syndrome Due to Influenza A (H1N1) Infection in
      Patients After Kidney Transplantation: A Report of Five Cases.
AB  - BACKGROUND In the general population, swine influenza is a self-limited
      infection. Patients after kidney transplantation, however, are at increased risk
      for complications and mortality from influenza A (H1N1). Acute respiratory
      distress syndrome (ARDS) complicates up to 55% of influenza-related pneumonia in
      hospitalized patients and carries a mortality of 40-46%. We describe our
      experience in intensive care of kidney transplant patients with ARDS complicating
      influenza A (H1N1) pneumonia during a flu outbreak. CASE REPORT Five adult post
      kidney transplantation patients with progressive respiratory failure admitted to
      the ICU between February 2016 and April 2016 were included in this
      retrospectively analysis. All patients had influenza A (H1N1) viral pneumonia
      (confirmed with RT-PCR) complicated by ARDS and septic shock with multiple organ
      dysfunction syndrome. None of the patients received seasonal influenza vaccines.
      All patients had negative rapid influenza bedside tests, which resulted in delay
      of administration of antiviral therapy prior to admission to the ICU. All
      patients were managed with a lung protective ventilation strategy (average days
      of mechanical ventilation, 17.6+/-15.3). Three patients required additional
      therapies for refractory hypoxemia, including high positive end-expiratory
      pressure and prone positioning. Extracorporeal membrane oxygenation was not
      implemented. Treatment with oseltamivir was added to a broad-spectrum antibiotic
      on the first to the fifth day of intensive care. Despite these measures, all
      patients eventually died. CONCLUSIONS Despite great progress in the management of
      ARDS, based mostly on advanced mechanical ventilation, early antiviral treatment
      of pneumonia caused by influenza A (H1N1) and annual vaccinations seem essential
      in prevention and management of influenza A (H1N1) infection among kidney
      transplant recipients.

PMID- 29599423
TI  - Atypical Presentation of Gelsolin Amyloidosis in a Man of African Descent with a
      Novel Mutation in the Gelsolin Gene.
AB  - BACKGROUND Gelsolin amyloidosis is a very rare systemic disease presenting with a
      pathognomonic triad of corneal lattice dystrophy, cutis laxa, and polyneuropathy.
      The disease is mostly restricted to a Finnish population with known mutations
      (G654A, G654T) in exon 4 of the gelsolin gene. The mutations lead to errors in
      protein processing and folding, and ultimately leads to deposition of an
      amyloidogenic fragment in the extracellular space, causing the symptoms of
      disease. CASE REPORT We present a case of gelsolin amyloidosis in a male of
      African descent with an atypical clinical presentation including fevers, skin
      rash, polyneuropathy, and anemia. Gelsolin amyloidosis was diagnosed based on
      mass spectrometry of tissue samples. Importantly, a novel mutation in the
      gelsolin gene (C1375G) in exon 10 was found in this patient. His atypical
      presentation can possibly be attributed to the presence of a novel mutation in
      the gelsolin gene as the likely underlying cause of the syndrome. PCR primers
      were used to amplify the gelsolin gene from genomic DNA. Purified PCR products
      were then shipped to Eton Biosciences (San Diego, CA) for sequencing. CONCLUSIONS
      This study carries several important lessons relevant to the practice of
      medicine. First, the differential diagnosis for multisystem disease presentations
      should always include amyloidosis. Second, despite what has been uncovered about
      the molecular biology of disease, there is always more that can be discovered.
      Finally, further work to verify the link between this mutation and the clinical
      syndrome is still needed, as are effective treatments for this disease.

PMID- 29599424
TI  - Epidemiology and Seasonality of Respiratory Viruses Detected from Children with
      Respiratory Tract Infections in Wuxi, East China.
AB  - BACKGROUND Respiratory tract infections (RTIs) are the major causes of mortality
      and morbidity in children and lead to hospitalization in developing countries.
      However, little is known about the epidemiology and seasonality of respiratory
      viruses in the pediatric population in Wuxi, East China. MATERIAL AND METHODS We
      included all patients 14 years of age and below who presented with signs and
      symptoms of RTIs between January 2010 and December 2016. During this period, a
      total of 2160 children treated in Wuxi No. 2 People's Hospital were involved in
      our study. The clinical and sociodemographic data were recorded to describe the
      frequency and seasonality. Respiratory specimens were tested by multiplex real
      time PCR assays for virus identification. RESULTS More than 30% (35.19%, 760
      samples) of the specimens showed evidence of infection with viruses, including
      respiratory syncytial virus (368 samples), influenza virus A (114 samples),
      influenza virus B (115 samples), parainfluenza virus I (29 samples),
      parainfluenza virus II (39 samples), parainfluenza virus III (13 samples), and
      adenovirus (82 samples); 48.99% of the children infected with viruses were under
      12 months of age. Viruses were detected throughout all the year, with a peak in
      winter. CONCLUSIONS Our study found that RSV is the most important cause of RTIs
      in our region during winter. Our data provide a comprehensive understanding of
      the epidemiology and seasonality of virus, which may help to reduce the use of
      antibiotics and implement an effective approach for prevention, control, and
      treatment of RTIs, especially during its peak season.

PMID- 29599425
TI  - Two-component anomalous Hall effect in a magnetically doped topological
      insulator.
AB  - The anomalous Hall (AH) effect measurement has emerged as a powerful tool to gain
      deep insights into magnetic materials, such as ferromagnetic metals, magnetic
      semiconductors, and magnetic topological insulators (TIs). In Mn-doped Bi2Se3,
      however, the AH effect has never been reported despite a lot of previous studies.
      Here we report the observation of AH effect in (Bi,Mn)2Se3 thin films and show
      that the sign of AH resistances changes from positive to negative as the Mn
      concentration is increased. The positive and negative AH resistances are found to
      coexist in a crossover regime. Such a two-component AH effect and the sign
      reversal can also be obtained by electrical gating of lightly doped samples. Our
      results provide an important basis for understanding the puzzling interplay
      between the surface states, the bulk states, and various magnetic doping effects,
      as well as competing magnetic orders in magnetically doped TIs.

PMID- 29599426
TI  - Occupational and leisure time physical inactivity and the risk of type II
      diabetes and hypertension among Mexican adults: A prospective cohort study.
AB  - : There is a lack of longitudinal data linking physical inactivity and chronic
      diseases among Mexicans. OBJECTIVE: To examine the relationship between total,
      leisure and occupational moderate-to-vigorous physical activity (MVPA) and
      incidence of type II diabetes (T2D) and hypertension in the Mexico City Diabetes
      Study. Study design and population. A prospective cohort study was conducted from
      1989 to 2009 among 2282 men and non-pregnant women residing in six low-income
      neighborhoods in Mexico City. MAIN OUTCOME: Incidence of T2D and hypertension.
      RESULTS: After controlling for confounders, <1 MET/min/week of MVPA during
      leisure time was associated with higher risk of hypertension (HR 1.29, CI 95%
      1.01, 1.66) and T2D (HR 1.31 CI 95% 1.00, 1.74). In addition, accumulating <1
      MET/min/week of occupational MVPA was associated with higher risk of hypertension
      (HR 1.47, CI 95% 1.13, 1.90). CONCLUSION: The absence of leisure and occupational
      MVPA was associated with an increased risk of hypertension. However, no
      associations were found between occupational MVPA and T2D.

PMID- 29599427
TI  - A new artificial diet for western corn rootworm larvae is compatible with and
      detects resistance to all current Bt toxins.
AB  - Insect resistance to transgenic crops is a growing concern for farmers,
      regulatory agencies, the seed industry, and researchers. Since 2009, instances of
      field-evolved Bt resistance or cross resistance have been documented for each of
      the four Bt proteins available for western corn rootworm (WCR), a major insect
      pest. To characterize resistance, WCR populations causing unexpected damage to Bt
      maize are evaluated in plant and/or diet toxicity assays. Currently, it is not
      possible to make direct comparisons of data from different Bt proteins due to
      differing proprietary artificial diets. Our group has developed a new, publicly
      available diet (WCRMO-1) with improved nutrition for WCR larvae. For the current
      manuscript, we tested the compatibility of all Bt proteins currently marketed for
      WCR on the WCRMO-1 diet and specific proprietary diets corresponding to each
      toxin using a susceptible colony of WCR. We also tested WCR colonies selected for
      resistance to each protein to assess the ability of the diet toxicity assay to
      detect Bt resistance. The WCRMO-1 diet is compatible with each of the proteins
      and can differentiate resistant colonies from susceptible colonies for each
      protein. Our diet allows researchers to monitor resistance without the
      confounding nutritional differences present between diets.

PMID- 29599428
TI  - Temperature and Monsoon Tango in a Tropical Stalagmite: Last Glacial-Interglacial
      Climate Dynamics.
AB  - High-resolution paleoclimate data on stable isotopes in a stalagmite were coupled
      to glycerol dialkyl glycerol tetraethers (GDGTs). The Indian Summer Monsoon (ISM)
      transitioned from limited rainfall during the Last Glacial Maximum (LGM) to
      intense precipitation during early Holocene (22 to 6 ka). This was associated
      with changes in stalagmite growth, abundance of branched (br) and isoprenoid
      (iso) GDGTs, as well as delta18O, delta13C, Sr/Ca and GDGT-derived signals
      providing both temperature and moisture information. The reconstructed mean
      annual air temperature (MAAT) of the most modern stalagmite sample at ~19 
      degrees C, matches the surface and cave MAAT, but was ~4  degrees C lower during
      LGM. Warming at the end of LGM occurred before ISM strengthened and indicate 6 ka
      lag consistent with sea surface temperature records. The isotope records during
      the Younger Dryas show rapid progressions to dry conditions and weak monsoons,
      but these shifts are not coupled to TEX86. Moreover, change to wetter and
      stronger ISM, along with warmer Holocene conditions are not continuous indicating
      a decoupling of local temperatures from ISM.

PMID- 29599429
TI  - Temperature induced crossing in the optical bandgap of mono and bilayer MoS2 on
      SiO2.
AB  - Photoluminescence measurements in mono- and bilayer-MoS2 on SiO2 were undertaken
      to determine the thermal effect of the MoS2/SiO2 interface on the optical
      bandgap. The energy and intensity of the photoluminescence from monolayer MoS2
      were lower and weaker than those from bilayer MoS2 at low temperatures, whilst
      the opposite was true at high temperatures above 200 K. Density functional theory
      calculations suggest that the observed optical bandgap crossover is caused by a
      weaker substrate coupling to the bilayer than to the monolayer.

PMID- 29599430
TI  - Helraiser intermediates provide insight into the mechanism of eukaryotic
      replicative transposition.
AB  - Helitrons are eukaryotic DNA transposons that have profoundly affected genome
      variability via capture and mobilization of host genomic sequences. Defining
      their mode of action is therefore important for understanding how genome
      landscapes evolve. Sequence similarities with certain prokaryotic mobile elements
      suggest a "rolling circle" mode of transposition, involving only a single
      transposon strand. Using the reconstituted Helraiser transposon to study Helitron
      transposition in cells and in vitro, we show that the donor site must be double
      stranded and that single-stranded donors will not suffice. Nevertheless,
      replication and integration assays demonstrate the use of only one of the
      transposon donor strands. Furthermore, repeated reuse of Helraiser donor sites
      occurs following DNA synthesis. In cells, circular double-stranded intermediates
      that serve as transposon donors are generated and replicated by Helraiser
      transposase. Cell-free experiments demonstrate strand-specific cleavage and
      strand transfer, supporting observations made in cells.

PMID- 29599432
TI  - Information-to-work conversion by Maxwell's demon in a superconducting circuit
      quantum electrodynamical system.
AB  - Information thermodynamics bridges information theory and statistical physics by
      connecting information content and entropy production through measurement and
      feedback control. Maxwell's demon is a hypothetical character that uses
      information about a system to reduce its entropy. Here we realize a Maxwell's
      demon acting on a superconducting quantum circuit. We implement quantum non
      demolition projective measurement and feedback operation of a qubit and verify
      the generalized integral fluctuation theorem. We also evaluate the conversion
      efficiency from information gain to work in the feedback protocol. Our experiment
      constitutes a step toward experimental studies of quantum information
      thermodynamics in artificially made quantum machines.

PMID- 29599431
TI  - Two-dimensional analysis provides molecular insight into flower scent of Lilium
      'Siberia'.
AB  - Lily is a popular flower around the world not only because of its elegant
      appearance, but also due to its appealing scent. Little is known about the
      regulation of the volatile compound biosynthesis in lily flower scent. Here, we
      conducted an approach combining two-dimensional analysis and weighted gene co
      expression network analysis (WGCNA) to explore candidate genes regulating flower
      scent production. In the approach, changes of flower volatile emissions and
      corresponding gene expression profiles at four flower developmental stages and
      four circadian times were both captured by GC-MS and RNA-seq methods. By
      overlapping differentially-expressed genes (DEGs) that responded to flower scent
      changes in flower development and circadian rhythm, 3,426 DEGs were initially
      identified to be candidates for flower scent production, of which 1,270 were
      predicted as transcriptional factors (TFs). The DEGs were further correlated to
      individual flower volatiles by WGCNA. Finally, 37, 41 and 90 genes were
      identified as candidate TFs likely regulating terpenoids, phenylpropanoids and
      fatty acid derivatives productions, respectively. Moreover, by WGCNA several
      genes related to auxin, gibberellins and ABC transporter were revealed to be
      responsible for flower scent production. Thus, this strategy provides an
      important foundation for future studies on the molecular mechanisms involved in
      floral scent production.

PMID- 29599434
TI  - Coherent changes of wintertime surface air temperatures over North Asia and North
      America.
AB  - The surface temperature variance and its potential change with global warming are
      most prominent in winter over Northern Hemisphere mid-high latitudes. Consistent
      wintertime surface temperature variability has been observed over large areas in
      Eurasia and North America on a broad range of time scales. However, it remains a
      challenge to quantify where and how the coherent change of temperature anomalies
      occur over the two continents. Here we demonstrate the coherent change of
      wintertime surface temperature anomalies over North Asia and the central-eastern
      parts of North America for the period from 1951 to 2015. This is supported by the
      results from the empirical orthogonal function analysis of surface temperature
      and temperature trend anomalies over the Northern Hemisphere extratropical lands
      and the timeseries analysis of the regional averaged temperature anomalies over
      North Asia and the Great Plains and Great Lakes. The Asian-Bering-North American
      (ABNA) teleconnection provides a pathway to connect the regional temperature
      anomalies over the two continents. The ABNA is also responsible for the decadal
      variation of the temperature relationship between North Asia and North America.

PMID- 29599433
TI  - Chemical tunnel-splitting-engineering in a dysprosium-based molecular nanomagnet.
AB  - Total control over the electronic spin relaxation in molecular nanomagnets is the
      ultimate goal in the design of new molecules with evermore realizable
      applications in spin-based devices. For single-ion lanthanide systems, with
      strong spin-orbit coupling, the potential applications are linked to the
      energetic structure of the crystal field levels and quantum tunneling within the
      ground state. Structural engineering of the timescale of these tunneling events
      via appropriate design of crystal fields represents a fundamental challenge for
      the synthetic chemist, since tunnel splittings are expected to be suppressed by
      crystal field environments with sufficiently high-order symmetry. Here, we report
      the long missing study of the effect of a non-linear (C4) to pseudo-linear (D4d)
      change in crystal field symmetry in an otherwise chemically unaltered dysprosium
      complex. From a purely experimental study of crystal field levels and electronic
      spin dynamics at milliKelvin temperatures, we demonstrate the ensuing threefold
      reduction of the tunnel splitting.

PMID- 29599435
TI  - Improved efficiency of in situ protein analysis by proximity ligation using
      UnFold probes.
AB  - We have redesigned probes for in situ proximity ligation assay (PLA), resulting
      in more efficient localized detection of target proteins. In situ PLA depends on
      recognition of target proteins by pairs of antibody-oligonucleotide conjugates
      (PLA probes), which jointly give rise to DNA circles that template localized
      rolling circle amplification reactions. The requirement for dual recognition of
      the target proteins improves selectivity by ignoring any cross-reactivity not
      shared by the antibodies, and it allows detection of protein-protein interactions
      and post-translational modifications. We herein describe an improved design of
      the PLA probes -UnFold probes - where all elements required for formation of
      circular DNA strands are incorporated in the probes. Premature interactions
      between the UnFold probes are prevented by including an enzymatic "unfolding"
      step in the detection reactions. This allows DNA circles to form by pairs of
      reagents only after excess reagents have been removed. We demonstrate the
      performance of UnFold probes for detection of protein-protein interactions and
      post-translational modifications in fixed cells and tissues, revealing
      considerably more efficient signal generation. We also apply the UnFold probes to
      detect IL-6 in solution phase after capture on solid supports, demonstrating
      increased sensitivity over both normal sandwich enzyme-linked immunosorbent
      assays and conventional PLA assays.

PMID- 29599436
TI  - SIRT6 facilitates directional telomere movement upon oxidative damage.
AB  - Oxidative damage to telomeres leads to telomere attrition and genomic
      instability, resulting in poor cell viability. Telomere dynamics contribute to
      the maintenance of telomere integrity; however, whether oxidative damage induces
      telomere movement and how telomere mobility is regulated remain poorly
      understood. Here, we show that oxidative damage at telomeres triggers directional
      telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is
      required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO)
      cells show neither damage-induced telomere movement nor chromatin decondensation
      at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation
      mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as
      well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to
      damaged telomeres, which appears to promote chromatin decondensation independent
      of its deacetylase activity. Together, our results suggest that SIRT6 plays a
      role in the regulation of telomere movement upon oxidative damage, shedding new
      light onto the function of SIRT6 in telomere maintenance.

PMID- 29599437
TI  - Predicting affective valence using cortical hemodynamic signals.
AB  - Ascribing affective valence to stimuli or mental states is a fundamental property
      of human experiences. Recent neuroimaging meta-analyses favor the workspace
      hypothesis for the neural underpinning of valence, in which both positive and
      negative values are encoded by overlapping networks but are associated with
      different patterns of activity. In the present study, we further explored this
      framework using functional near-infrared spectroscopy (fNIRS) in conjunction with
      multivariate analyses. We monitored the fronto-temporal and occipital hemodynamic
      activity of 49 participants during the viewing of affective images (passive
      condition) and during the imagination of affectively loaded states (active
      condition). Multivariate decoding techniques were applied to determine whether
      affective valence is encoded in the cortical areas assessed. Prediction
      accuracies of 89.90 +/- 13.84% and 85.41 +/- 14.43% were observed for positive
      versus neutral comparisons, and of 91.53 +/- 13.04% and 81.54 +/- 16.05% for
      negative versus neutral comparisons (passive/active conditions, respectively).
      Our results are consistent with previous studies using other neuroimaging
      modalities that support the affective workspace hypothesis and the notion that
      valence is instantiated by the same network, regardless of whether the affective
      experience is passively or actively elicited.

PMID- 29599438
TI  - The secretome from bovine mammosphere-derived cells (MDC) promotes angiogenesis,
      epithelial cell migration, and contains factors associated with defense and
      immunity.
AB  - Treatment of bovine mastitis with intramammary antibiotics is common, yet several
      concerns exist including failed efficacy for individual hosts or pathogens and
      the inability of approved drugs to revert mastitis-induced tissue damage to
      healthy tissue capable of returning to full milk production. These issues, in
      addition to aspects of public health such as accidental antibiotic residues in
      saleable milk and the potential for antimicrobial resistance, support the need to
      find alternative therapies for this costly disease. This study shows that the
      secretome, or collective factors, produced by mammosphere-derived cells (MDC)
      promotes angiogenesis, epithelial cell migration, and contains proteins
      associated with immunity and defense; all of which are necessary for healing
      damaged mammary gland tissue. Furthermore, we found that the MDC secretome
      remains effective after freezing and thawing, enhancing its therapeutic
      potential. Our results provide a foundation for further characterization of the
      individual secreted factors and the rationale for using the MDC secretome as a
      complementary treatment for bovine mastitis.

PMID- 29599439
TI  - Fiber-optic implant for simultaneous fluorescence-based calcium recordings and
      BOLD fMRI in mice.
AB  - Despite the growing popularity of blood oxygen level-dependent (BOLD) functional
      MRI (fMRI), understanding of its underlying principles is still limited. This
      protocol describes a technique for simultaneous measurement of neural activity
      using fluorescent calcium indicators together with the corresponding hemodynamic
      BOLD fMRI response in the mouse brain. Our early work using small-molecule
      fluorophores in rats gave encouraging results but was limited to acute
      measurements using synthetic dyes. Our latest procedure combines fMRI with
      optical detection of cell-type-specific virally delivered GCaMP6, a genetically
      encoded calcium indicator (GECI). GCaMP6 fluorescence, which increases upon
      calcium binding, is collected by a chronically implanted optical fiber, allowing
      longitudinal studies in mice. The chronic implant, placed horizontally on the
      skull, has an angulated tip that reflects light into the brain and is connected
      via fiber optics to a remote optical setup. The technique allows access to the
      neocortex and does not require adaptations of commercial MRI hardware. The hybrid
      approach permits fiber-optic calcium recordings with simultaneous artifact-free
      BOLD fMRI with full brain coverage and 1-s temporal resolution using standard
      gradient-echo echo-planar imaging (GE-EPI) sequences. The method provides robust,
      cell-type-specific readouts to link neural activity to BOLD signals, as
      emonstrated for task-free ('resting-state') conditions and in response to hind
      paw stimulation. These results highlight the power of fiber photometry combined
      with fMRI, which we aim to further advance in this protocol. The approach can be
      easily adapted to study other molecular processes using suitable fluorescent
      indicators.

PMID- 29599440
TI  - Genome-wide analysis of replication timing by next-generation sequencing with E/L
      Repli-seq.
AB  - This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014);
      doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate
      their DNA content during S phase, following a defined program called replication
      timing (RT). Early- and late-replicating regions differ in terms of mutation
      rates, transcriptional activity, chromatin marks and subnuclear position.
      Moreover, RT is regulated during development and is altered in diseases. Here, we
      describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is
      a rapid, robust and relatively inexpensive protocol for analyzing RT by next
      generation sequencing (NGS), allowing genome-wide assessment of how cellular
      processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early
      and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is
      immunoprecipitated from both fractions and sequenced. Data processing leads to a
      single bedGraph file containing the ratio of nascent DNA from early versus late S
      phase fractions. The results are comparable to those of Repli-chip, with the
      additional benefits of genome-wide sequence information and an increased dynamic
      range. We also provide computational pipelines for downstream analyses, for
      parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT
      allelic asynchrony, and for direct comparison to Repli-chip data. This protocol
      can be performed in up to 3 d before sequencing, and requires basic cellular and
      molecular biology skills, as well as a basic understanding of Unix and R.

PMID- 29599441
TI  - The successes and future prospects of the linear antisense RNA amplification
      methodology.
AB  - It has been over a quarter of a century since the introduction of the linear RNA
      amplification methodology known as antisense RNA (aRNA) amplification. Whereas
      most molecular biology techniques are rapidly replaced owing to the fast-moving
      nature of development in the field, the aRNA procedure has become a base that can
      be built upon through varied uses of the technology. The technique was originally
      developed to assess RNA populations from small amounts of starting material,
      including single cells, but over time its use has evolved to include the
      detection of various cellular entities such as proteins, RNA-binding-protein
      associated cargoes, and genomic DNA. In this Perspective we detail the linear
      aRNA amplification procedure and its use in assessing various components of a
      cell's chemical phenotype. This procedure is particularly useful in efforts to
      multiplex the simultaneous detection of various cellular processes. These efforts
      are necessary to identify the quantitative chemical phenotype of cells that
      underlies cellular function.

PMID- 29599442
TI  - On-chip microfluidic production of cell-sized liposomes.
AB  - In this protocol, we describe a recently developed on-chip microfluidic method to
      form monodisperse, cell-sized, unilamellar, and biocompatible liposomes with
      excellent encapsulation efficiency. Termed octanol-assisted liposome assembly
      (OLA), it resembles bubble-blowing on a microscopic scale. Hydrodynamic flow
      focusing of two immiscible fluid streams (an aqueous phase and a lipid-containing
      1-octanol phase) by orthogonal outer aqueous streams gives rise to double
      emulsion droplets. As the lipid bilayer assembles along the interface, each
      emulsion droplet quickly evolves into a liposome and a 1-octanol droplet. OLA has
      several advantages as compared with other on-chip techniques, such as a very fast
      liposome maturation time (a few minutes), a relatively straightforward and
      completely on-chip setup, and a biologically relevant liposome size range (5-20
      MUm). Owing to the entire approach being on-chip, OLA enables high-throughput
      liposome production (typical rate of tens of Hz) using low sample volumes (~10
      MUl). For prolonged on-chip experimentation, liposomes are subsequently purified
      by removing the 1-octanol droplets. For device fabrication, a reusable silicon
      template is produced in a clean room facility using electron-beam lithography
      followed by dry reactive ion etching, which takes ~3 h. The patterned silicon
      template is used to prepare polydimethylsiloxane (PDMS)-based microfluidic
      devices in the wet lab, followed by a crucial surface treatment; the whole
      process takes ~2 d. Liposomes can be produced in ~1 h and further manipulated,
      depending on the experimental setup. OLA offers an ideal microfluidic platform
      for diverse bottom-up biotechnology studies by enabling creation of synthetic
      cells, microreactors and bioactive cargo delivery systems, and also has potential
      as an analytical tool.

PMID- 29599443
TI  - Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes.
AB  - RNAs are well-suited to act as cellular sensors that detect and respond to
      metabolite changes in the environment, due to their ability to fold into complex
      structures. Here, we introduce a genome-wide strategy called PARCEL that
      experimentally identifies RNA aptamers in vitro, in a high-throughput manner. By
      applying PARCEL to a collection of prokaryotic and eukaryotic organisms, we have
      revealed 58 new RNA aptamers to three key metabolites, greatly expanding the list
      of natural RNA aptamers. The newly identified RNA aptamers exhibit significant
      sequence conservation, are highly structured and show an unexpected prevalence in
      coding regions. We identified a prokaryotic precursor tmRNA that binds vitamin B2
      (FMN) to facilitate its maturation, as well as eukaryotic mRNAs that bind and
      respond to FMN, suggesting FMN as the second RNA-binding ligand to affect
      eukaryotic expression. PARCEL results show that RNA-based sensing and gene
      regulation is more widespread than previously appreciated in different organisms.

PMID- 29599444
TI  - Environmental complexity buffers against stress-induced negative judgement bias
      in female chickens.
AB  - Cognitive processes are often biased by emotions. In humans, affective disorders
      are accompanied by pessimistic judgement, while optimistic judgement is linked to
      emotional stability. Similar to humans, animals tend to interpret ambiguous
      stimuli negatively after experiencing stressful events, although the long-lasting
      impact on judgement bias has rarely been investigated. We measure judgement bias
      in female chicks (Gallus gallus domesticus) after exposure to cold stress, and
      before and after exposure to additional unpredictable stressors. Additionally, we
      explore if brain monoamines can explain differences in judgement bias. Chicks
      exposed to cold stress did not differ in judgement bias compared to controls, but
      showed sensitivity to additional stressors by having higher motivation for social
      reinstatement. Environmental complexity reduced stress-induced negative judgement
      bias, by maintaining an optimistic bias in individuals housed in complex
      conditions even after stress exposure. Moreover, judgement bias was related to
      dopamine turnover rate in mesencephalon, with higher activity in individuals that
      had a more optimistic response. These results demonstrate that environmental
      complexity can buffer against negative effects of additive stress and that
      dopamine relates to judgement bias in chicks. These results reveal that both
      internal and external factors can mediate emotionally biased judgement in
      animals, thus showing similarities to findings in humans.

PMID- 29599445
TI  - Recruitment kinetics of the homologous recombination pathway in procyclic forms
      of Trypanosoma brucei after ionizing radiation treatment.
AB  - One of the most important mechanisms for repairing double-strand breaks (DSBs) in
      model eukaryotes is homologous recombination (HR). Although the genes involved in
      HR have been found in Trypanosoma brucei and studies have identified some of the
      proteins that participate in this HR pathway, the recruitment kinetics of the HR
      machinery onto DNA during DSB repair have not been clearly elucidated in this
      organism. Using immunofluorescence, protein DNA-bound assays, and DNA content
      analysis, we established the recruitment kinetics of the HR pathway in response
      to the DSBs generated by ionizing radiation (IR) in procyclic forms of T. brucei.
      These kinetics involved the phosphorylation of histone H2A and the sequential
      recruitment of the essential HR players Exo1, RPA, and Rad51. The process of DSB
      repair took approximately 5.5 hours. We found that DSBs led to a decline in the
      G2/M phase after IR treatment, concomitant with cell cycle arrest in the G1/S
      phase. This finding suggests that HR repairs DSBs faster than the other possible
      DSB repair processes that act during the G1/S transition. Taken together, these
      data suggest that the interplay between DNA damage detection and HR machinery
      recruitment is finely coordinated, allowing these parasites to repair DNA rapidly
      after DSBs during the late S/G2 proficient phases.

PMID- 29599446
TI  - Valence and spin states of iron are invisible in Earth's lower mantle.
AB  - Heterogeneity in Earth's mantle is a record of chemical and dynamic processes
      over Earth's history. The geophysical signatures of heterogeneity can only be
      interpreted with quantitative constraints on effects of major elements such as
      iron on physical properties including density, compressibility, and electrical
      conductivity. However, deconvolution of the effects of multiple valence and spin
      states of iron in bridgmanite (Bdg), the most abundant mineral in the lower
      mantle, has been challenging. Here we show through a study of a ferric-iron-only
      (Mg0.46Fe3+0.53)(Si0.49Fe3+0.51)O3 Bdg that Fe3+ in the octahedral site undergoes
      a spin transition between 43 and 53 GPa at 300 K. The resolved effects of the
      spin transition on density, bulk sound velocity, and electrical conductivity are
      smaller than previous estimations, consistent with the smooth depth profiles from
      geophysical observations. For likely mantle compositions, the valence state of
      iron has minor effects on density and sound velocities relative to major cation
      composition.

PMID- 29599447
TI  - High-resolution GPS tracking reveals sex differences in migratory behaviour and
      stopover habitat use in the Lesser Black-backed Gull Larus fuscus.
AB  - Sex-, size- or age-dependent variation in migration strategies in birds is
      generally expected to reflect differences in competitive abilities. Theoretical
      and empirical studies thereby focus on differences in wintering areas, by which
      individuals may benefit from avoiding food competition during winter or ensuring
      an early return and access to prime nesting sites in spring. Here, we use GPS
      tracking to assess sex- and size-related variation in the spatial behaviour of
      adult Lesser Black-backed Gulls (Larus fuscus) throughout their annual cycle. We
      did not find sex- or size-dependent differences in wintering area or the timing
      of spring migration. Instead, sexual differences occurred prior to, and during,
      autumn migration, when females strongly focussed on agricultural areas. Females
      exhibited a more protracted autumn migration strategy, hence spent more time on
      stopover sites and arrived 15 days later at their wintering areas, than males.
      This shift in habitat use and protracted autumn migration coincided with the
      timing of moult, which overlaps with chick rearing and migration. Our results
      suggest that this overlap between energy-demanding activities may lead females to
      perform a more prolonged autumn migration, which results in spatiotemporal
      differences in foraging habitat use between the sexes.

PMID- 29599449
TI  - Implications of TERT promoter mutations and telomerase activity in urothelial
      carcinogenesis.
AB  - Telomerase activity imparts eukaryotic cells with unlimited proliferation
      capacity, one of the cancer hallmarks. Over 90% of human urothelial carcinoma of
      the bladder (UCB) tumours are positive for telomerase activity. Telomerase
      activation can occur through several mechanisms. Mutations in the core promoter
      region of the human telomerase reverse transcriptase gene (TERT) cause telomerase
      reactivation in 60-80% of UCBs, whereas the prevalence of these mutations is
      lower in urothelial cancers of other origins. TERT promoter mutations are the
      most frequent genetic alteration across all stages of UCB, indicating a strong
      selection pressure during neoplastic transformation. TERT promoter mutations
      could arise during regeneration of normal urothelium and, owing to consequential
      telomerase reactivation, might be the basis of UCB initiation, which represents a
      new model of urothelial cancer origination. In the future, TERT promoter
      mutations and telomerase activity might have diagnostic and therapeutic
      applications in UCB.

PMID- 29599448
TI  - RodZ modulates geometric localization of the bacterial actin MreB to regulate
      cell shape.
AB  - In the rod-shaped bacterium Escherichia coli, the actin-like protein MreB
      localizes in a curvature-dependent manner and spatially coordinates cell-wall
      insertion to maintain cell shape, although the molecular mechanism by which cell
      width is regulated remains unknown. Here we demonstrate that the membrane protein
      RodZ regulates the biophysical properties of MreB and alters the spatial
      organization of E. coli cell-wall growth. The relative expression levels of MreB
      and RodZ change in a manner commensurate with variations in growth rate and cell
      width, and RodZ systematically alters the curvature-based localization of MreB
      and cell width in a concentration-dependent manner. We identify MreB mutants that
      alter the bending properties of MreB filaments in molecular dynamics simulations
      similar to RodZ binding, and show that these mutants rescue rod-like shape in the
      absence of RodZ alone or in combination with wild-type MreB. Thus, E. coli can
      control its shape and dimensions by differentially regulating RodZ and MreB to
      alter the patterning of cell-wall insertion, highlighting the rich regulatory
      landscape of cytoskeletal molecular biophysics.

PMID- 29599450
TI  - Application of biosurfactant from Bacillus subtilis C9 for controlling cladoceran
      grazers in algal cultivation systems.
AB  - Open algal cultivation platforms often suffer crop losses to herbivorous grazers
      that have potential to devastate biomass production within a few days. While a
      number of studies suggest synthetic chemicals as control agents for voracious
      algal grazers, environmental and safety concerns associated with the use of these
      chemicals encourage the exploration of alternative biological control agents. We
      hereby propose the application of a biosurfactant produced by Bacillus subtilis
      C9 (referred to as C9-biosurfactant) for controlling cladoceran grazers commonly
      found in algal cultivation systems. The results indicated that C9-biosurfactant
      completely eradicated Daphnia pulex and Moina macrocopa within 24 hours when
      concentrations were equal to or exceeded 6 mg/L. Moreover, supplying C9
      biosurfactant into the cultures of selected algal species with and without
      cladoceran grazers indicated no adverse effect of C9-biosurfactant on the growth
      and lipid productivity of algal crops, while cladocerans were selectively
      controlled by C9-biosurfactant even under the presence of their prey. These
      results thus indicate that C9-biosurfactant could be an effective biocontrol
      agent for cladoceran grazers at industrial algal cultivation.

PMID- 29599451
TI  - Supervised Learning Classifiers for Electrical Impedance-based Bladder State
      Detection.
AB  - Urinary Incontinence affects over 200 million people worldwide, severely
      impacting the quality of life of individuals. Bladder state detection technology
      has the potential to improve the lives of people with urinary incontinence by
      alerting the user before voiding occurs. To this end, the objective of this study
      is to investigate the feasibility of using supervised machine learning
      classifiers to determine the bladder state of 'full' or 'not full' from
      electrical impedance measurements. Electrical impedance data was obtained from
      computational models and a realistic experimental pelvic phantom. Multiple
      datasets with increasing complexity were formed for varying noise levels in
      simulation. 10-Fold testing was performed on each dataset to classify 'full' and
      'not full' bladder states, including phantom measurement data. Support vector
      machines and k-Nearest-Neighbours classifiers were compared in terms of accuracy,
      sensitivity, and specificity. The minimum and maximum accuracies across all
      datasets were 73.16% and 100%, respectively. Factors that contributed most to
      misclassification were the noise level and bladder volumes near the threshold of
      'full' or 'not full'. This paper represents the first study to use machine
      learning for bladder state detection with electrical impedance measurements. The
      results show promise for impedance-based bladder state detection to support those
      living with urinary incontinence.

PMID- 29599452
TI  - Direct antiviral properties of TLR ligands against HBV replication in immune
      competent hepatocytes.
AB  - Current therapies for chronic hepatitis B virus (HBV) infections are effective at
      decreasing the viral load in serum, but do not lead to viral eradication. Recent
      studies highlighted the therapeutic or "adjuvant" potential of immune-modulators.
      Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR)
      agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or
      differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists.
      Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW)
      (TLR3/MDA5-ligand) were the best at reducing all HBV parameters. No or little
      viral rebound was observed after treatment arrest, implying a long-lasting effect
      on cccDNA. We also tested Riboxxol that features improved TLR3 specificity
      compared to poly(I:C)-(HMW). This agonist demonstrated a potent antiviral effect
      in HBV-infected PHH. Whereas, poly(I:C)-(HMW) and Pam3CSK4 mainly induced the
      expression of classical genes from the interferon or NF-kappaB pathway
      respectively, Riboxxol had a mixed phenotype. Moreover, TLR2 and TLR3 ligands can
      activate hepatocytes and immune cells, as demonstrated by antiviral cytokines
      produced by stimulated hepatocytes and peripheral blood mononuclear cells. In
      conclusion, our data highlight the potential of innate immunity activation in the
      direct control of HBV replication in hepatocytes, and support the development of
      TLR-based antiviral strategies.

PMID- 29599454
TI  - A neutrophil motility assay for early diagnosis of sepsis.

PMID- 29599453
TI  - Functional cyclophilin D moderates platelet adhesion, but enhances the lytic
      resistance of fibrin.
AB  - In the course of thrombosis, platelets are exposed to a variety of activating
      stimuli classified as 'strong' (e.g. thrombin and collagen) or 'mild' (e.g. ADP).
      In response, activated platelets adhere to injured vasculature, aggregate, and
      stabilise the three-dimensional fibrin scaffold of the expanding thrombus. Since
      'strong' stimuli also induce opening of the mitochondrial permeability transition
      pore (MPTP) in platelets, the MPTP-enhancer Cyclophilin D (CypD) has been
      suggested as a critical pharmacological target to influence thrombosis. However,
      it is poorly understood what role CypD plays in the platelet response to 'mild'
      stimuli which act independently of MPTP. Furthermore, it is unknown how CypD
      influences platelet-driven clot stabilisation against enzymatic breakdown
      (fibrinolysis). Here we show that treatment of human platelets with Cyclosporine
      A (a cyclophilin-inhibitor) boosts ADP-induced adhesion and aggregation, while
      genetic ablation of CypD in murine platelets enhances adhesion but not
      aggregation. We also report that platelets lacking CypD preserve their integrity
      in a fibrin environment, and lose their ability to render clots resistant against
      fibrinolysis. Our results indicate that CypD has opposing haemostatic roles
      depending on the stimulus and stage of platelet activation, warranting a careful
      design of any antithrombotic strategy targeting CypD.

PMID- 29599455
TI  - Comprehensive characterization of glutamine synthetase-mediated selection for the
      establishment of recombinant CHO cells producing monoclonal antibodies.
AB  - To characterize a glutamine synthetase (GS)-based selection system, monoclonal
      antibody (mAb) producing recombinant CHO cell clones were generated by a single
      round of selection at various methionine sulfoximine (MSX) concentrations (0, 25,
      and 50 MUM) using two different host cell lines (CHO-K1 and GS-knockout CHO).
      Regardless of the host cell lines used, the clones selected at 50 MUM MSX had the
      lowest average specific growth rate and the highest average specific production
      rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high
      producing clones could be generated in the absence of MSX using GS-knockout CHO
      with an improved selection stringency. Regardless of the host cell lines used,
      the clones selected at various MSX concentrations showed no significant
      difference in the GS, heavy chain, and light chain gene copies (P > 0.05).
      Furthermore, there was no correlation between the specific mAb productivity and
      these three gene copies (R2 <= 0.012). Taken together, GS-mediated gene
      amplification does not occur in a single round of selection at a MSX
      concentration up to 50 MUM. The use of the GS-knockout CHO host cell line
      facilitates the rapid generation of high producing clones with reduced production
      of lactate and ammonia in the absence of MSX.

PMID- 29599456
TI  - To grow, or not to grow.

PMID- 29599458
TI  - CRISPR-based genomic tools for the manipulation of genetically intractable
      microorganisms.
AB  - Genetic manipulation of microorganisms has been crucial in understanding their
      biology, yet for many microbial species, robust tools for comprehensive genetic
      analysis were lacking until the advent of CRISPR-Cas-based gene editing
      techniques. In this Progress article, we discuss advances in CRISPR-based
      techniques for the genetic analysis of genetically intractable microorganisms,
      with an emphasis on mycobacteria, fungi and parasites. We discuss how CRISPR
      based analyses in these organisms have enabled the discovery of novel gene
      functions, the investigation of genetic interaction networks and the
      identification of virulence factors.

PMID- 29599457
TI  - Streptococcus pneumoniae: transmission, colonization and invasion.
AB  - Streptococcus pneumoniae has a complex relationship with its obligate human host.
      On the one hand, the pneumococci are highly adapted commensals, and their main
      reservoir on the mucosal surface of the upper airways of carriers enables
      transmission. On the other hand, they can cause severe disease when bacterial and
      host factors allow them to invade essentially sterile sites, such as the middle
      ear spaces, lungs, bloodstream and meninges. Transmission, colonization and
      invasion depend on the remarkable ability of S. pneumoniae to evade or take
      advantage of the host inflammatory and immune responses. The different stages of
      pneumococcal carriage and disease have been investigated in detail in animal
      models and, more recently, in experimental human infection. Furthermore,
      widespread vaccination and the resulting immune pressure have shed light on
      pneumococcal population dynamics and pathogenesis. Here, we review the
      mechanistic insights provided by these studies on the multiple and varied
      interactions of the pneumococcus and its host.

PMID- 29599459
TI  - The social network of microorganisms - how auxotrophies shape complex
      communities.
AB  - Microorganisms engage in complex interactions with other organisms and their
      environment. Recent studies have shown that these interactions are not limited to
      the exchange of electron donors. Most microorganisms are auxotrophs, thus relying
      on external nutrients for growth, including the exchange of amino acids and
      vitamins. Currently, we lack a deeper understanding of auxotrophies in
      microorganisms and how nutrient requirements differ between different strains and
      different environments. In this Opinion article, we describe how the study of
      auxotrophies and nutrient requirements among members of complex communities will
      enable new insights into community composition and assembly. Understanding this
      complex network over space and time is crucial for developing strategies to
      interrogate and shape microbial communities.

PMID- 29599460
TI  - High-speed and on-chip graphene blackbody emitters for optical communications by
      remote heat transfer.
AB  - High-speed light emitters integrated on silicon chips can enable novel
      architectures for silicon-based optoelectronics, such as on-chip optical
      interconnects, and silicon photonics. However, conventional light sources based
      on compound semiconductors face major challenges for their integration with a
      silicon-based platform because of their difficulty of direct growth on a silicon
      substrate. Here we report ultra-high-speed (100-ps response time), highly
      integrated graphene-based on-silicon-chip blackbody emitters in the near-infrared
      region including telecommunication wavelength. Their emission responses are
      strongly affected by the graphene contact with the substrate depending on the
      number of graphene layers. The ultra-high-speed emission can be understood by
      remote quantum thermal transport via surface polar phonons of the substrates. We
      demonstrated real-time optical communications, integrated two-dimensional array
      emitters, capped emitters operable in air, and the direct coupling of optical
      fibers to the emitters. These emitters can open new routes to on-Si-chip, small
      footprint, and high-speed emitters for highly integrated optoelectronics and
      silicon photonics.

PMID- 29599461
TI  - Using human brain activity to guide machine learning.
AB  - Machine learning is a field of computer science that builds algorithms that
      learn. In many cases, machine learning algorithms are used to recreate a human
      ability like adding a caption to a photo, driving a car, or playing a game. While
      the human brain has long served as a source of inspiration for machine learning,
      little effort has been made to directly use data collected from working brains as
      a guide for machine learning algorithms. Here we demonstrate a new paradigm of
      "neurally-weighted" machine learning, which takes fMRI measurements of human
      brain activity from subjects viewing images, and infuses these data into the
      training process of an object recognition learning algorithm to make it more
      consistent with the human brain. After training, these neurally-weighted
      classifiers are able to classify images without requiring any additional neural
      data. We show that our neural-weighting approach can lead to large performance
      gains when used with traditional machine vision features, as well as to
      significant improvements with already high-performing convolutional neural
      network features. The effectiveness of this approach points to a path forward for
      a new class of hybrid machine learning algorithms which take both inspiration and
      direct constraints from neuronal data.

PMID- 29599462
TI  - Recurrence of task-related electroencephalographic activity during post-training
      quiet rest and sleep.
AB  - Offline reactivation of task-related neural activity has been demonstrated in
      animals but is difficult to directly observe in humans. We sought to identify
      potential electroencephalographic (EEG) markers of offline memory processing in
      human subjects by identifying a set of characteristic EEG topographies
      ("microstates") that occurred as subjects learned to navigate a virtual maze. We
      hypothesized that these task-related microstates would appear during post-task
      periods of rest and sleep. In agreement with this hypothesis, we found that one
      task-related microstate was increased in post-training rest and sleep compared to
      baseline rest, selectively for subjects who actively learned the maze, and not in
      subjects performing a non-learning control task. Source modeling showed that this
      microstate was produced by activity in temporal and parietal networks, which are
      known to be involved in spatial navigation. For subjects who napped after
      training, the increase in this task-related microstate predicted the magnitude of
      subsequent change in performance. Our findings demonstrate that task-related EEG
      patterns re-emerge during post-training rest and sleep.

PMID- 29599463
TI  - An explanation for the low proportion of tuberculosis that results from
      transmission between household and known social contacts.
AB  - We currently have little idea where Mycobacterium tuberculosis (Mtb) transmission
      occurs in high incidence settings. Molecular studies suggest that only around 8
      19% of transmission to adults occurs within-household, or between known social
      contacts. This contrasts with findings from social-contact studies, which show
      that substantial proportions of contact time occur in households, workplaces and
      schools. A mathematical model of social-contact behaviour and Mtb transmission
      was developed, incorporating variation in susceptibility and infectiousness.
      Three types of contact were simulated: household, repeated (individuals outside
      household contacted repeatedly with daily-monthly frequency) and non-repeated.
      The model was parameterised using data from Cape Town, South Africa, on mean and
      variance in contact numbers and contact durations, by contact type, and fitted to
      an estimate of overdispersion in numbers of secondary cases ('superspreading') in
      Cape Town. Household, repeated, and non-repeated contacts contributed 36%, 13%,
      and 51% of contact time, and 13%, 8%, and 79% of disease, respectively. Results
      suggest contact saturation, exacerbated by long disease durations and
      superspreading, cause the high proportion of transmission between non-repeated
      contacts. Household and social-contact tracing is therefore unlikely to reach
      most tuberculosis cases. A better understanding of transmission locations, and
      methods to identify superspreaders, are urgently required to improve tuberculosis
      prevention strategies.

PMID- 29599464
TI  - Real-time distribution of pelagic fish: combining hydroacoustics, GIS and spatial
      modelling at a fine spatial scale.
AB  - Understanding spatial distribution of organisms in heterogeneous environment
      remains one of the chief issues in ecology. Spatial organization of freshwater
      fish was investigated predominantly on large-scale, neglecting important local
      conditions and ecological processes. However, small-scale processes are of an
      essential importance for individual habitat preferences and hence structuring
      trophic cascades and species coexistence. In this work, we analysed the real-time
      spatial distribution of pelagic freshwater fish in the Rimov Reservoir (Czechia)
      observed by hydroacoustics in relation to important environmental predictors
      during 48 hours at 3-h interval. Effect of diurnal cycle was revealed of highest
      significance in all spatial models with inverse trends between fish distribution
      and predictors in day and night in general. Our findings highlighted daytime
      pelagic fish distribution as highly aggregated, with general fish preferences for
      central, deep and highly illuminated areas, whereas nighttime distribution was
      more disperse and fish preferred nearshore steep sloped areas with higher depth.
      This turnover suggests prominent movements of significant part of fish assemblage
      between pelagic and nearshore areas on a diel basis. In conclusion,
      hydroacoustics, GIS and spatial modelling proved as valuable tool for predicting
      local fish distribution and elucidate its drivers, which has far reaching
      implications for understanding freshwater ecosystem functioning.

PMID- 29599465
TI  - Evaluation of Screened Lignin-degrading Fungi for the Biological Pretreatment of
      Corn Stover.
AB  - The biological pretreatment of lignocellulosic biomass is a low-cost and eco
      friendly method for facilitating enzymatic hydrolysis. In this study, strains
      with lignin depletion capability were screened using a high-throughput screening
      method. Sixty-three strains were screened out and Myrothecium verrucaria secreted
      three lignin-degrading enzymes simultaneously during the bio-pretreatment
      process. The activity levels of laccase, lignin peroxidase and manganese
      peroxidase were 6.61, 0.78 and 1.31 U g-1 dry biomass. The content of lignin in
      corn stover decreased by 42.30% after bio-pretreatment, and the conversion rate
      increased by 123.84% during the subsequent saccharification process in comparison
      with the untreated corn stover. Furthermore, the effects of bio-pretreatment on
      the structure of corn stover were presented using a scanning electron microscope
      (SEM), Brunauer-Emmet-Teller (BET), X-ray diffractometer (XRD) and Fourier
      transform infrared spectroscopy (FTIR). The results showed that M.V. is a
      promising lignin-degrading fungus. This research demonstrated an efficient
      pretreatment approach for enhancing the enzymatic saccharification of corn
      stover.

PMID- 29599466
TI  - A high-brightness large-diameter graphene coated point cathode field emission
      electron source.
AB  - There have been several long-standing problems of cold field emission sources for
      electron microscopy and lithography that have prevented their widespread use,
      such as their inherent ultrahigh vacuum condition requirement (<10-9 torr),
      relatively poor current stability and rapid emission decay. This paper presents a
      cold field emission electron source which overcomes these problems based upon
      using a graphene-coated nickel point cathode. Preliminary experiments demonstrate
      that it provides stable emission for relatively large tip diameters (micron
      sizes), can operate in high vacuum conditions (>10-8 torr) and has an ultralow
      work function value of 1.10 +/- 0.07 eV. It has an estimated reduced brightness
      value of 1.46 * 109 A m-2 sr-1 V-1 for cathode tip-radius of 170 nm and the
      measured energy spread ranges from 0.246 eV to 0.420 eV for a tip radii range of
      260 nm to 500 nm, which is comparable to state-of-the-art conventional cold field
      emission sources.

PMID- 29599468
TI  - Enhanced Ti0.84Ta0.16N diffusion barriers, grown by a hybrid sputtering technique
      with no substrate heating, between Si(001) wafers and Cu overlayers.
AB  - We compare the performance of conventional DC magnetron sputter-deposited (DCMS)
      TiN diffusion barriers between Cu overlayers and Si(001) substrates with
      Ti0.84Ta0.16N barriers grown by hybrid DCMS/high-power impulse magnetron
      sputtering (HiPIMS) with substrate bias synchronized to the metal-rich portion of
      each pulse. DCMS power is applied to a Ti target, and HiPIMS applied to Ta. No
      external substrate heating is used in either the DCMS or hybrid DCMS/HiPIMS
      process in order to meet future industrial thermal-budget requirements. Barrier
      efficiency in inhibiting Cu diffusion into Si(001) while annealing for 1 hour at
      temperatures between 700 and 900  degrees C is investigated using scanning
      electron microscopy, X-ray diffraction, four-point-probe sheet resistance
      measurements, transmission electron microscopy, and energy-dispersive X-ray
      spectroscopy profiling. Ti0.84Ta0.16N barriers are shown to prevent large-scale
      Cu diffusion at temperatures up to 900  degrees C, while conventional TiN
      barriers fail at <=700  degrees C. The improved performance of the Ti0.84Ta0.16N
      barrier is due to film densification resulting from HiPIMS pulsed irradiation of
      the growing film with synchronized Ta ions. The heavy ion bombardment dynamically
      enhances near-surface atomic mixing during barrier-layer deposition.

PMID- 29599467
TI  - Relationship between the morphology of the foveal avascular zone, retinal
      structure, and macular circulation in patients with diabetes mellitus.
AB  - Diabetic Retinopathy (DR) is an extremely severe and common degenerative disease.
      The purpose of this study was to quantify the relationship between various
      parameters including the Foveal Avascular Zone (FAZ) morphology, retinal layer
      thickness, and retinal hemodynamic properties in healthy controls and patients
      with diabetes mellitus (DM) with and with no mild DR (MDR) using Spectral-Domain
      Optical Coherence Tomography (Spectralis SDOCT, Heidelberg Engineering GmbH,
      Germany) and the Retinal Function Imager (Optical Imaging, Ltd., Rehovot,
      Israel). Our results showed a higher FAZ area and diameter in MDR patients. Blood
      flow analysis also showed that there is a significantly smaller venous blood flow
      velocity in MDR patients. Also, a significant difference in roundness was
      observed between DM and MDR groups supporting the development of asymmetrical FAZ
      expansion with worsening DR. Our results suggest a potential anisotropy in the
      mechanical properties of the diabetic retina with no retinopathy that may trigger
      the FAZ elongation in a preferred direction resulting in either thinning or
      thickening of intraretinal layers in the inner and outer segments of the retina
      as a result of autoregulation. A detailed understanding of these relationships
      may facilitate earlier detection of DR, allowing for preservation of vision and
      better clinical outcomes.

PMID- 29599469
TI  - Scalable synthesis enabling multilevel bio-evaluations of natural products for
      discovery of lead compounds.
AB  - Challenges in the development of anti-cancer chemotherapeutics continue to exist,
      particularly with respect to adverse effects and development of resistance,
      underlining the need for novel drugs with good safety profiles. Natural products
      have proven to be a fertile ground for exploitation, and development of anti
      cancer drugs from structurally complex natural products holds promise.
      Unfortunately, this approach is often hindered by low isolation yields and
      limited information from preliminary cell-based assays. Here we report a concise
      and scalable synthesis of a series of low-abundance Isodon diterpenoids (a large
      class of natural products with over 1000 members isolated from the herbs of genus
      Isodon, which are well-known folk medicines for the treatment of inflammation and
      cancer), including eriocalyxin B, neolaxiflorin L and xerophilusin I. These
      scalable syntheses enable multilevel bio-evaluation of the natural products, in
      which we identify neolaxiflorin L as a promising anti-cancer drug candidate.

PMID- 29599470
TI  - An advanced human in vitro co-culture model for translocation studies across the
      placental barrier.
AB  - Although various drugs, environmental pollutants and nanoparticles (NP) can cross
      the human placental barrier and may harm the developing fetus, knowledge on
      predictive placental transfer rates and the underlying transport pathways is
      mostly lacking. Current available in vitro placental transfer models are often
      inappropriate for translocation studies of macromolecules or NPs and do not
      consider barrier function of placental endothelial cells (EC). Therefore, we
      developed a human placental in vitro co-culture transfer model with tight layers
      of trophoblasts (BeWo b30) and placental microvascular ECs (HPEC-A2) on a low
      absorbing, 3 um porous membrane. Translocation studies with four model substances
      and two polystyrene (PS) NPs across the individual and co-culture layers revealed
      that for most of these compounds, the trophoblast and the EC layer both
      demonstrate similar, but not additive, retention capacity. Only the paracellular
      marker Na-F was substantially more retained by the BeWo layer. Furthermore,
      simple shaking, which is often applied to mimic placental perfusion, did not
      alter translocation kinetics compared to static exposure. In conclusion, we
      developed a novel placental co-culture model, which provides predictive values
      for translocation of a broad variety of molecules and NPs and enables valuable
      mechanistic investigations on cell type-specific placental barrier function.

PMID- 29599471
TI  - Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an
      Ultrastructural Evaluation.
AB  - We recently identified mucosal mast cell and eosinophil hyperplasia in
      association with a duodenal impaired barrier function in functional dyspepsia
      (FD). We aimed to further describe the implication of these immune cells by
      assessing their activation state at the ultrastructural level and by evaluating
      the association between impaired epithelial integrity and immune activation.
      Duodenal biopsies were obtained from 24 FD patients and 37 healthy controls. The
      ultrastructure of mast cells and eosinophils was analyzed by transmission
      electron microscopy. Transepithelial electrical resistance and paracellular
      permeability were measured to evaluate epithelial barrier function. The type of
      degranulation in eosinophils and mast cells was piecemeal. Eosinophils displayed
      higher degree of degranulation in FD patients than in controls (p < 0.0001).
      Quantification revealed a decreased granular density in eosinophils of FD
      patients (p < 0.0001). The degree of degranulation in mast cells was similar in
      both groups. However, a more heterogeneous profile was found in the FD group (p <
      0.0001). No association between epithelial integrity and the number and
      activation state of mucosal eosinophils and mast cells was found. We demonstrated
      ultrastructural changes in degranulation state of eosinophils and mast cells,
      suggesting that eosinophil and mast cell activation play a role in the
      pathophysiology of FD.

PMID- 29599472
TI  - Examination of Csr regulatory circuitry using epistasis analysis with RNA-seq
      (Epi-seq) confirms that CsrD affects gene expression via CsrA, CsrB and CsrC.
AB  - The Csr global regulatory system coordinates gene expression in response to
      metabolic status. This system utilizes the RNA binding protein CsrA to regulate
      gene expression by binding to transcripts of structural and regulatory genes,
      thus affecting their structure, stability, translation, and/or transcription
      elongation. CsrA activity is controlled by sRNAs, CsrB and CsrC, which sequester
      CsrA away from other transcripts. CsrB/C levels are partly determined by their
      rates of turnover, which requires CsrD to render them susceptible to RNase E
      cleavage. Previous epistasis analysis suggested that CsrD affects gene expression
      through the other Csr components, CsrB/C and CsrA. However, those conclusions
      were based on a limited analysis of reporters. Here, we reassessed the global
      behavior of the Csr circuitry using epistasis analysis with RNA seq (Epi-seq).
      Because CsrD effects on mRNA levels were entirely lost in the csrA mutant and
      largely eliminated in a csrB/C mutant under our experimental conditions, while
      the majority of CsrA effects persisted in the absence of csrD, the original model
      accounts for the global behavior of the Csr system. Our present results also
      reflect a more nuanced role of CsrA as terminal regulator of the Csr system than
      has been recognized.

PMID- 29599473
TI  - Epigallocatechin-3-gallate alleviates bladder overactivity in a rat model with
      metabolic syndrome and ovarian hormone deficiency through mitochondria apoptosis
      pathways.
AB  - Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder
      storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound
      in green tea, has been shown to protect against ovarian hormone deficiency
      induced overactive bladder (OAB). The present study investigated oxidative stress
      induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism
      underlying the protective effect of EGCG (10 umol/kg/day) on bladder
      overactivity. Rats were fed with high fat high sugar (HFHS) diet to induce MetS
      and received ovariectomy surgery to deprive ovarian hormone. By dieting with HFHS
      for 6 months, rats developed MetS and OAB. MetS + OVX deteriorated bladder
      storage dysfunction more profound than MetS alone. MetS and MetS + OVX rats
      showed over-expression of inflammatory and fibrosis markers (1.7~3.8-fold of
      control). EGCG pretreatment alleviated storage dysfunction, and protected the
      bladders from MetS and OVX - induced interstitial fibrosis changes. Moreover, OVX
      exacerbated MetS related bladder apoptosis (2.3~4.5-fold of control; 1.8~2.6-fold
      of Mets group), enhances oxidative stress markers (3.6~4.3-fold of control;
      1.8~2.2-fold of Mets group) and mitochondrial enzyme complexes subunits (1.8~3.7
      fold of control; 1.5~3.4-fold of Mets group). EGCG pretreatment alleviated
      bladder apoptosis, attenuated oxidative stress, and reduced the mitochondrial and
      endoplasmic reticulum apoptotic signals. In conclusions, HFHS feeding and ovarian
      hormone deficiency enhances the generation of oxidative stress mediated through
      mitochondrial pathway. EGCG reduced the generation of oxidative stress and
      lessened bladder overactivity.

PMID- 29599475
TI  - Precision oncology in non-small-cell lung cancer: opportunities and challenges.

PMID- 29599474
TI  - Outer membrane vesicles from beta-lactam-resistant Escherichia coli enable the
      survival of beta-lactam-susceptible E. coli in the presence of beta-lactam
      antibiotics.
AB  - Outer membrane vesicles (OMVs) containing various bacterial compounds are
      released from mainly gram-negative bacteria. Secreted OMVs play important roles
      in the ability of a bacterium to defend itself, and thus contribute to the
      survival of bacteria in a community. In this study, we collected OMVs from beta
      lactam antibiotic-resistant Escherichia coli established by conjugation assay and
      the parental beta-lactam antibiotic-susceptible strain, and performed comparative
      proteomic analysis to examine whether these OMVs carried beta-lactam-resistant
      compounds. We also investigated whether both types of OMVs could protect
      susceptible cells from beta-lactam-induced death and/or directly degrade beta
      lactam antibiotics. Several proteins that can be involved in degrading beta
      lactam antibiotics were more abundant in OMVs from beta-lactam-resistant E. coli,
      and thus OMVs from beta-lactam resistant E. coli could directly and dose
      dependently degrade beta-lactam antibiotics and fully rescue beta-lactam
      susceptible E. coli and other bacterial species from beta-lactam antibiotic
      induced growth inhibition. Taken together, present study demonstrate that OMVs
      from beta-lactam-resistant E. coli play important roles in survival of antibiotic
      susceptible bacteria against beta-lactam antibiotics. This finding may pave the
      way for new efforts to combat the current global spread of antibiotic
      resistances, which is considered to be a significant public health threat.

PMID- 29599476
TI  - The emerging clinical relevance of genomics in cancer medicine.
AB  - The combination of next-generation sequencing and advanced computational data
      analysis approaches has revolutionized our understanding of the genomic
      underpinnings of cancer development and progression. The coincident development
      of targeted small molecule and antibody-based therapies that target a cancer's
      genomic dependencies has fuelled the transition of genomic assays into clinical
      use in patients with cancer. Beyond the identification of individual targetable
      alterations, genomic methods can gauge mutational load, which might predict a
      therapeutic response to immune-checkpoint inhibitors or identify cancer-specific
      proteins that inform the design of personalized anticancer vaccines. Emerging
      clinical applications of cancer genomics include monitoring treatment responses
      and characterizing mechanisms of resistance. The increasing relevance of genomics
      to clinical cancer care also highlights several considerable challenges,
      including the need to promote equal access to genomic testing.

PMID- 29599477
TI  - The world's largest High Arctic lake responds rapidly to climate warming.
AB  - Using a whole-watershed approach and a combination of historical, contemporary,
      modeled and paleolimnological datasets, we show that the High Arctic's largest
      lake by volume (Lake Hazen) has succumbed to climate warming with only a ~1 
      degrees C relative increase in summer air temperatures. This warming deepened the
      soil active layer and triggered large mass losses from the watershed's glaciers,
      resulting in a ~10 times increase in delivery of glacial meltwaters, sediment,
      organic carbon and legacy contaminants to Lake Hazen, a >70% decrease in lake
      water residence time, and near certainty of summer ice-free conditions.
      Concomitantly, the community assemblage of diatom primary producers in the lake
      shifted dramatically with declining ice cover, from shoreline benthic to open
      water planktonic species, and the physiological condition of the only fish
      species in the lake, Arctic Char, declined significantly. Collectively, these
      changes place Lake Hazen in a biogeochemical, limnological and ecological regime
      unprecedented within the past ~300 years.

PMID- 29599479
TI  - Boson peak, heterogeneity and intermediate-range order in binary SiO2-Al2O3
      glasses.
AB  - In binary aluminosilicate liquids and glasses, heterogeneity on intermediate
      length scale is a crucial factor for optical fiber performance, determining the
      lower limit of optical attenuation and Rayleigh scattering, but also clustering
      and precipitation of optically active dopants, for example, in the fabrication of
      high-power laser gain media. Here, we consider the low-frequency vibrational
      modes of such materials for assessing structural heterogeneity on molecular
      scale. We determine the vibrational density of states VDoS g(omega) using low
      temperature heat capacity data. From correlation with low-frequency Raman
      spectroscopy, we obtain the Raman coupling coefficient. Both experiments allow
      for the extraction of the average dynamic correlation length as a function of
      alumina content. We find that this value decreases from about 3.9 nm to 3.3 nm
      when mildly increasing the alumina content from zero (vitreous silica) to 7 mol%.
      At the same time, the average inter-particle distance increases slightly due to
      the presence of oxygen tricluster species. In accordance with Loewensteinian
      dynamics, this proves that mild alumina doping increases structural homogeneity
      on molecular scale.

PMID- 29599478
TI  - Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+
      in healthy middle-aged and older adults.
AB  - Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate
      for enzymes involved in the beneficial effects of regular calorie restriction on
      healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability
      has been proposed as a strategy for improving cardiovascular and other
      physiological functions with aging in humans. Here we provide the evidence in a 2
      * 6-week randomized, double-blind, placebo-controlled, crossover clinical trial
      that chronic supplementation with the NAD+ precursor vitamin, nicotinamide
      riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in
      healthy middle-aged and older adults. Our results also provide initial insight
      into the effects of chronic NR supplementation on physiological function in
      humans, and suggest that, in particular, future clinical trials should further
      assess the potential benefits of NR for reducing blood pressure and arterial
      stiffness in this group.

PMID- 29599480
TI  - Fungal spore diversity reflects substrate-specific deposition challenges.
AB  - Sexual spores are important for the dispersal and population dynamics of fungi.
      They show remarkable morphological diversity, but the underlying forces driving
      spore evolution are poorly known. We investigated whether trophic status and
      substrate associations are associated with morphology in 787 macrofungal genera.
      We show that both spore size and ornamentation are associated with trophic
      specialization, so that large and ornamented spores are more probable in
      ectomycorrhizal than in saprotrophic genera. This suggests that spore
      ornamentation facilitates attachment to arthropod vectors, which ectomycorrhizal
      species may need to reach lower soil layers. Elongated spore shapes are more
      common in saprotrophic taxa, and genera associated with above ground substrates
      are more likely to have allantoid (curved elongated) spores, probably to lower
      the risk of wash out by precipitation. Overall, our results suggest that safe
      arrival on specific substrates is a more important driver of evolution in spore
      morphology than dispersal per se.

PMID- 29599481
TI  - Developing transmission line equations of oxygen transport for predicting oxygen
      distribution in the arterial system.
AB  - The oxygen content in the arterial system plays a significant role in determining
      the physiological status of a human body. Understanding the oxygen concentration
      distribution in the arterial system is beneficial for the prevention and
      intervention of vascular disease. However, the oxygen concentration in the
      arteries could not be noninvasively monitored in clinical research. Although the
      oxygen concentration distribution in a vessel could be obtained from a three
      dimensional (3D) numerical simulation of blood flow coupled with oxygen
      transport, a 3D numerical simulation of the systemic arterial tree is complicated
      and requires considerable computational resources and time. However, the lumped
      parameter model of oxygen transport derived from transmission line equations of
      oxygen transport requires fewer computational resources and less time to
      numerically predict the oxygen concentration distribution in the systemic
      arterial tree. In this study, transmission line equations of oxygen transport are
      developed according to the theory of oxygen transport in the vessel, and fluid
      transmission line equations are used as the theoretical reference for the
      development. The transmission line equations of oxygen transport could also be
      regarded as the theoretical basis for developing lumped parameter models of other
      substances in blood.

PMID- 29599482
TI  - The Notch inhibitor cowanin accelerates nicastrin degradation.
AB  - Aberrant activation of Notch signaling contributes to the pathogenesis of several
      different types of cancer, and Notch pathway inhibitors may have significant
      therapeutic potential. Using a unique cell-based assay system, we isolated twelve
      compounds, including one new natural product from Garcinia speciosa, that inhibit
      the Notch signaling pathway. HES1 and HES5 are target genes of the Notch cascade,
      and compound 2, referred to as cowanin, decreased the protein levels of HES1 and
      HES5 in assay cells. Furthermore, cowanin (2) showed potent cytotoxicity against
      human leukemic HPB-ALL cells. The Notch signaling inhibitory activity of cowanin
      (2) is linked to the increased degradation of nicastrin, which is one of the
      components of the gamma-secretase complex. To the best of our knowledge, this is
      the first example of a compound with Notch pathway inhibitory activity mediated
      by nicastrin degradation.

PMID- 29599483
TI  - Identification of The Aberrantly Expressed LncRNAs in Hepatocellular Carcinoma: A
      Bioinformatics Analysis Based on RNA-sequencing.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent subtypes of liver
      cancer worldwide. LncRNAs have been demonstrated to be associated with the
      progression of HCC, but a systematic identification and characterization of their
      clinical roles and molecular mechanisms in HCC has not been conducted. In this
      study, the aberrantly expressed lncRNAs in HCC tissues were analyzed based on
      TCGA RNA-seq data. 1162 lncRNAs were found to be aberrantly expressed in HCC
      tissues, including 232 down-regulated lncRNAs and 930 up-regulated lncRNAs. The
      top 5 lncRNAs with the highest diagnostic accuracy were further analyzed to
      evaluate their clinical value and potential mechanism in HCC. Kaplan-Meier curves
      showed that higher expressions of DDX11-AS1 and AC092171.4 were in correlation
      with poorer survival in HCC patients. Significant difference was also observed
      when comparing the expression levels of DDX11-AS1 and SFTA1P in different
      clinical parameters (p < 0.05). GO analysis showed that genes regulated by the 5
      lncRNAs were enriched in certain pathways, such as PI3K pathway. Moreover, GSEA
      analysis on the expression of DDX11-AS1 showed that DDX11-AS1 affected the gene
      expressions involved in HCC proliferation, differentiation and cell cycle,
      indicating an essential role of DDX11-AS1 in hepatocarcinogenesis.

PMID- 29599484
TI  - Prophylactic ketamine alters nucleotide and neurotransmitter metabolism in brain
      and plasma following stress.
AB  - Recently, we have shown that ketamine given prior to stress exposure protects
      against the development of depressive-like behavior in mice. These data suggest
      that it may be possible to prevent the induction of affective disorders before
      they develop by administering prophylactic pharmaceuticals, a relatively nascent
      and unexplored strategy for psychiatry. Here, we performed metabolomics analysis
      of brain and plasma following prophylactic ketamine treatment in order to
      identify markers of stress resilience enhancement. We administered prophylactic
      ketamine in mice to buffer against fear expression. Following behavioral
      analyses, untargeted metabolomic profiling was performed on both hemispheres of
      the prefrontal cortex (PFC) and the hippocampus (HPC), and plasma. We found that
      prophylactic ketamine attenuated learned fear. Eight metabolites were changed in
      the PFC and HPC upon ketamine treatment. Purine and pyrimidine metabolism were
      most significantly changed in the HPC, PFC, and, interestingly, plasma of mice
      two weeks after prophylactic administration. Moreover, most precursors to
      inhibitory neurotransmitters were increased whereas precursors to excitatory
      neurotransmitters were decreased. Strikingly, these long-term metabolomic changes
      were not observed when no stressor was administered. Our results suggest that
      prophylactic treatment differentially affects purine and pyrimidine metabolism
      and neurotransmission in brain and plasma following stress, which may underlie
      the long-lasting resilience to stress induced by a single injection of ketamine.
      These data may provide novel targets for prophylactic development, and indicate
      an interaction effect of prophylactic ketamine and stress. To our knowledge, this
      is the first study that identifies metabolomic alterations and biomarker
      candidates for prophylactic ketamine efficacy in mice.

PMID- 29599485
TI  - Neurocognitive effects of umami: association with eating behavior and food
      choice.
AB  - Free glutamate, a key substance underlying the umami taste of foods, fulfills a
      number of physiological functions related to energy balance. Previous
      experimental studies have shown that intake of a broth or soup supplemented with
      monosodium glutamate (MSG) prior to a meal can decrease appetite and food intake,
      particularly in women with propensity to overeat and gain weight. In this study,
      we examined potential neurocognitive mechanisms underlying this effect. We
      evaluated changes after intake of a chicken broth with or without MSG added
      (MSG+/MSG-) in a sample of healthy young women. Subjects were assessed with a
      food-modified computerized inhibitory control task, a buffet meal test with eye
      tracking, and brain responses during a food choice paradigm evaluated with
      functional neuroimaging. We found evidence for improvement in key parameters
      related to inhibitory control following intake of the MSG+ broth, particularly in
      subjects with high levels of eating disinhibition, who also showed lower intake
      of saturated fat during the meal. Additionally, consumption of the MSG+ broth led
      to a reduction of the rate of fixation switches between plates at the meal, and
      increased engagement of a brain region in the left dorsolateral prefrontal cortex
      previously associated with successful self-control during dietary decisions.
      Altogether, these results, while preliminary, suggest potential facilitating
      effects of glutamate (MSG) on cognitive executive processes that are relevant for
      the support of healthy eating behaviors and food choice.

PMID- 29599487
TI  - Baclofen and gastroesophageal reflux disease: seeing the forest through the
      trees.
AB  - Baclofen has been shown to decrease reflux events and increase lower esophageal
      sphincter pressure, yet has never established a clear role in the treatment of
      gastroesophageal reflux disease (GERD). Lei and colleagues have shown in a recent
      elegant study that baclofen reduces the frequency and initiation of secondary
      peristalsis and heightens esophageal sensitivity to capsaicin-mediated
      stimulation. These findings may help explain both the benefit of baclofen in
      conditions such as rumination and supragastric belching, as well as the apparent
      lack of benefit of baclofen and other GABAB agonists in long-term treatment of
      GERD.

PMID- 29599486
TI  - USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A
      stabilization.
AB  - Histone chaperone ASF1A has been reported to be dysregulated in multiple tumors;
      however, the underlying molecular mechanism that how the abundance and function
      of ASF1A are regulated remains unclear. Here we report that ASF1A is physically
      associated with USP52, which is previously identified as a pseudo-deubiquitinase.
      Interestingly, we demonstrate that USP52 is a bona fide ubiquitin-specific
      protease, and USP52 promotes ASF1A deubiquitination and stabilization. USP52
      promoted ASF1A stabilization facilitates chromatin assembly and favors cell cycle
      progression. Additionally, we find that USP52 is overexpressed in breast
      carcinomas, and its level of expression correlates with that of ASF1A. Moreover,
      we reveal that impairment of USP52-promoted ASF1A stabilization results in growth
      arrest of breast cancer cells and sensitizes these cells to DNA damage. Our
      experiments identify USP52 as a truly protein deubiquitinase, uncover a molecular
      mechanism of USP52 in chromatin assembly, and reveal a potential role of USP52 in
      breast carcinogenesis.

PMID- 29599488
TI  - Author Correction: Prevalence and characteristics of hypoxic hepatitis in the
      largest single-centre cohort of avian influenza A(H7N9) virus-infected patients
      with severe liver impairment in the intensive care unit.
AB  - Correction to: Emerging Microbes & Infections (2016) 5:e1;
      https://doi.org/10.1038/emi.2016.1 ; Article published online 6 January 2016.

PMID- 29599489
TI  - Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent
      Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal
      Women.
AB  - Acute myocardial infarction (AMI) is often underdiagnosed in women. It is
      therefore of interest to identify biomarkers that indicate increased risk of AMI
      and thereby help clinicians to have additional focus on the difficult AMI
      diagnosis. Type I Collagen, a component of the cardiac extracellular matrix, is
      cleaved by matrix metalloproteinases (MMPs) generating the neo-epitope C1M. We
      investigated the association between serum-C1M and AMI and evaluated whether C1M
      is a prognostic marker for outcome following AMI. This study is based on The
      Prospective Epidemiological Risk Factor (PERF) Study including postmenopausal
      women. 316 out of 5,450 women developed AMI within the follow-up period (14
      years, median). A multivariate Cox analysis assessed association between serum
      C1M and AMI, and re-infaction or death subsequent to AMI. The risk of AMI
      increased by 18% (p = 0.03) when serum-C1M was doubled and women in the highest
      quartile had a 33% increased risk compared to those in the low quartiles (p =
      0.025). Serum-C1M was, however not related to reinfarction or death subsequent to
      AMI. In this study C1M was be an independent risk factor for AMI. Measuring MMP
      degraded type I collagen could be useful for prediction of increased risk of AMI
      if replicated in other cohorts.

PMID- 29599490
TI  - Interaction of Glycolipids with the Macrophage Surface Receptor Mincle - a
      Systematic Molecular Dynamics Study.
AB  - Synthetic analogues of mycobacterial trehalose-dimycolate such as trehalose acyl
      esters have been proposed as novel adjuvants for vaccination. They induce an
      immune response by binding to the macrophage C-type lectin receptor Mincle. The
      binding site of trehalose is known, but there is yet only very limited structural
      information about the binding mode of the acyl esters. Here, we performed a
      systematic molecular dynamics study of trehalose mono-and diesters with different
      chain lengths. All acyl chains investigated exhibited a high flexibility and
      interacted almost exclusively with a hydrophobic groove on Mincle. Despite the
      limited length of this hydrophobic groove, the distal parts of the longer
      monoesters can still form additional interactions with this surface region due to
      their conformational flexibility. In diesters, a certain length of the second
      acyl chain is required to contact the hydrophobic groove. However, a stable
      concomitant accommodation of both acyl chains in the groove is hampered by the
      conformational rigidity of Mincle. Instead, multiple dynamic interaction modes
      are observed, in which the second acyl chain contributes to binding. This
      detailed structural information is considered helpful for the future design of
      more affine ligands that may foster the development of novel adjuvants.

PMID- 29599491
TI  - The immune contexture of hepatocellular carcinoma predicts clinical outcome.
AB  - The general relevance of the immune system for cancer development and therapy is
      increasingly recognized. However and although the immune contexture of most human
      cancer types has been determined, a global characterisation of the immune tumour
      microenvironment in hepatocellular carcinoma (HCC) is lacking. Equally,
      differences in the immune contexture of HCC between different patient subgroups
      and its effect on survival remain to be established. Here we report an in silico
      analysis of the immune contexture of human HCC. Using large deep sequencing HCC
      tumour, adjacent non-tumour and healthy liver high-dimensional data sets, we were
      able to reveal previously unrecognized differences in the immune contexture of
      HCC. Strikingly, we found that different etiologies and HCC stages were not
      associated with major changes in the immune contexture. In contrast, the presence
      of T cells and cytotoxic cells as well as the absence of macrophages and Th2
      cells positively correlated with patient survival. Based on these novel findings,
      we developed a prognostic score that accurately distinguishes between patients
      with good and poor survival. Our study provides the first global characterisation
      of the immune contexture of HCC and will have direct implications for future HCC
      therapies.

PMID- 29599492
TI  - No perceptual prioritization of non-nociceptive vibrotactile and visual stimuli
      presented on a sensitized body part.
AB  - High frequency electrical conditioning stimulation (HFS) is an experimental
      method to induce increased mechanical pinprick sensitivity in the unconditioned
      surrounding skin (secondary hyperalgesia). Secondary hyperalgesia is thought to
      be the result of central sensitization, i.e. increased responsiveness of
      nociceptive neurons in the central nervous system. Vibrotactile and visual
      stimuli presented in the area of secondary hyperalgesia also elicit enhanced
      brain responses, a finding that cannot be explained by central sensitization as
      it is currently defined. HFS may recruit attentional processes, which in turn
      affect the processing of all stimuli. In this study we have investigated whether
      HFS induces perceptual biases towards stimuli presented onto the sensitized arm
      by using Temporal Order Judgment (TOJ) tasks. In TOJ tasks, stimuli are presented
      in rapid succession on either arm, and participants have to indicate their
      perceived order. In case of a perceptual bias, the stimuli presented on the
      attended side are systematically reported as occurring first. Participants
      performed a tactile and a visual TOJ task before and after HFS. Analyses of
      participants' performance did not reveal any prioritization of the visual and
      tactile stimuli presented onto the sensitized arm. Our results provide therefore
      no evidence for a perceptual bias towards tactile and visual stimuli presented
      onto the sensitized arm.

PMID- 29599493
TI  - RING tetramerization is required for nuclear body biogenesis and PML sumoylation.
AB  - ProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains
      directly implicated in acute promyelocytic leukemia eradication. Most TRIM family
      members bind ubiquitin E2s and many acquire ligase activity upon RING
      dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray
      crystallography and SAXS characterization, we demonstrate that PML RING
      tetramerizes through highly conserved PML-specific sequences, which are required
      for NB assembly and PML sumoylation. Conserved residues implicated in RING
      dimerization of other TRIMs also contribute to PML tetramer stability. Wild-type
      PML rescues the ability of some RING mutants to form NBs as well as their
      sumoylation. Impaired RING tetramerization abolishes PML/RARA-driven
      leukemogenesis in vivo and arsenic-induced differentiation ex vivo. Our studies
      thus identify RING tetramerization as a key step in the NB macro-molecular
      scaffolding. They suggest that higher order RING interactions allow efficient
      UBC9 recruitment and thus change the biochemical nature of TRIM-facilitated post
      translational modifications.

PMID- 29599494
TI  - Response analysis of host Spodoptera exigua larvae to infection by Heliothis
      virescens ascovirus 3h (HvAV-3h) via transcriptome.
AB  - Heliothis virescens ascovirus 3 h (HvAV-3h), a dsDNA insect virus, belonging to
      the family Ascoviridae, can infect caterpillars of several Noctuidae species by
      ovipositing parasitoid wasps. In order to provide a comprehensive overview of the
      interactive responses of host larvae after infection by the ascovirus, a
      transcriptome analysis of Spodoptera exigua to HvAV-3h was conducted from 6 to
      168 hours post infection (hpi). Approximately 101.64 Gb of RNA sequencing (RNA
      seq) data obtained from infected and uninfected S. exigua larvae were used to
      perform a de novo transcriptome assembly, which generated approximately 62,258 S.
      exigua unigenes. Using differential gene expression analysis, it was determined
      that the majority of host transcripts were down-regulated beginning at 6 hpi and
      continuing throughout the infection period, although there was an increase in up
      regulated unigene number during the 12 to 72 hpi stage. It is noteworthy that the
      most abundantly enriched pathways in KEGG annotation were Metabolism terms,
      indicating that the host larval metabolic mechanisms were highly influenced post
      HvAV-3h infection. In addition, the host cuticle protein encoding unigenes were
      highly down-regulated in most of the situations, suggesting that the host larval
      cuticle synthesis were inhibited by the viral infection.

PMID- 29599495
TI  - Multilocus genetic profile in dopaminergic pathway modulates the striatum and
      working memory.
AB  - Dopamine is critical in pathophysiology and therapy of schizophrenia. Many
      studies have reported altered dopaminergic activity in the dorsal but not ventral
      striatum in schizophrenia. Based on the largest genome-wide association study of
      schizophrenia to date, we calculated the polygenic risk score (PGRS) of each
      subject in a healthy general group, including all variations in the set of
      functionally related genes involved in dopamine neurotransmitter system. We aimed
      to test whether the genetic variations in the dopaminergic pathway that have been
      identified as associated with schizophrenia are related to the function of the
      striatum and to working memory. We found that a higher PGRS was significantly
      associated with impairment in working memory. Moreover, resting-state functional
      connectivity analysis revealed that as the polygenic risk score increased, the
      connections between left putamen and caudate and the default mode network grew
      stronger, while the connections with the fronto-parietal network grew weaker. Our
      findings may shed light on the biological mechanism underlying the "dopamine
      hypothesis" of schizophrenia and provide some implications regarding the
      polygenic effects on the dopaminergic activity in the risk for schizophrenia.

PMID- 29599496
TI  - High fat diet alters Drosophila melanogaster sexual behavior and traits:
      decreased attractiveness and changes in pheromone profiles.
AB  - Sexual traits convey information about individual quality to potential mates.
      Environmental and genetic factors affect sexual trait expression and perception
      via effects on animal condition and health. High fat diet (HFD) is one
      environmental factor that adversely affects Drosophila melanogaster health, and
      its effects on animal health are mediated through conserved metabolic signaling
      pathways. HFD decreases female attractiveness, resulting in reduced male mating
      behaviors toward HFD females. HFD also affects the ability of males to judge mate
      attractiveness and likely alters fly condition and sexual traits to impact mating
      behavior. Here we show that HFD affects both visual (body size) and non-visual
      (pheromone profiles) sexual traits, which likely contribute to decreased fly
      attractiveness. We also demonstrate that adult-specific HFD effects on male mate
      preference can be rescued by changing metabolic signaling. These results
      demonstrate that HFD alters Drosophila sexual cues to reflect concurrent effects
      on condition and that less severe behavioral defects can be reversed by genetic
      manipulations that rescue fly health. This work expands on current knowledge of
      the role that metabolic signaling pathways play in linking animal health, sexual
      traits, and mating behavior, and provides a robust assay in a genetically
      tractable system to continue examining these processes.

PMID- 29599498
TI  - Polarized electron beams elastically scattered by atoms as a tool for testing
      fundamental predictions of quantum mechanics.
AB  - Quantum information theory deals with quantum noise in order to protect physical
      quantum bits (qubits) from its effects. A single electron is an emblematic
      example of a qubit, and today it is possible to experimentally produce polarized
      ensembles of electrons. In this paper, the theory of the polarization of electron
      beams elastically scattered by atoms is briefly summarized. Then the POLARe
      program suite, a set of computer programs aimed at the calculation of the spin
      polarization parameters of electron beams elastically interacting with atomic
      targets, is described. Selected results of the program concerning Ar, Kr, and Xe
      atoms are presented together with the comparison with experimental data about the
      Sherman function for low kinetic energy of the incident electrons (1.5eV-350eV).
      It is demonstrated that the quantum-relativistic theory of the polarization of
      electron beams elastically scattered by atoms is in good agreement with
      experimental data down to energies smaller than a few eV.

PMID- 29599497
TI  - Evaluation of a dimeric-cRGD peptide for targeted PET-CT imaging of peripheral
      angiogenesis in diabetic mice.
AB  - The alpha V  beta3 integrin plays an important role in many physiological
      functions and pathological disorders. alpha V  beta3 is minimally expressed in
      normal quiescent endothelial cells, but significantly upregulated during
      neovascularization. In this study, we evaluated a 64Cu-labeled dimeric cRGD
      tracer targeted at alpha V  beta3 integrin and report its applicability to assess
      peripheral angiogenesis in diabetes mellitus (DM). We established a murine model
      of type-1 DM characterized by elevated glucose, glycated serum protein (GSP), and
      glycated hemoglobin A1c (HbA1c). We demonstrated that our imaging probe is
      specific to alpha V  beta3 integrin under both normo- and hyperglycemic
      conditions. We found that the analysis of in vivo PET-CT images correlated well
      with gamma well counting (GWC). Both GWC and PET-CT imaging demonstrated
      increased uptake of 64Cu-NOTA-PEG4-cRGD2 in the ischemic hindlimb in contrast to
      non-ischemic control. GWC of the distal ischemic tissue from DM mice showed
      significantly lower probe accumulation than in non-DM mice. The
      immunofluorescence staining of the ischemic tissues showed a 3-fold reduction in
      CD31 and 4-fold reduction in the alpha V  beta3 expression in DM vs. non-DM
      animals. In conclusion, we successfully demonstrated that diabetes-associated
      reductions in peripheral angiogenesis can be non-invasively detected with PET-CT
      imaging using targeted dimeric-cRGD probe.

PMID- 29599499
TI  - Neurons in the Pigeon Nidopallium Caudolaterale Display Value-Related Activity.
AB  - We recorded from neurons in the nidopallium caudolaterale, the avian equivalent
      of the mammalian prefrontal cortex, in four birds. The birds were required to
      peck a stimulus that indicated the amount of reward they would receive (small or
      large) after a certain delay (short or long). We found that the activity of
      neurons in the nidopallium caudolaterale was modulated by the value of the reward
      that would be received based on the reward amount and the delay to reward. We
      found that value coding was most prominent during the presentation of the sample
      period, and less so during the delay period and during the presentation of the
      reward itself. Our findings support the view that activity in nidopallium
      caudolaterale reflects the encoding of the value of reward based on a combination
      of reward amount and delay to a reward.

PMID- 29599500
TI  - Association of induced abortion with preterm birth risk in first-time mothers.
AB  - Women who have previously had an induced abortion (IA) before their first birth
      have been associated with preterm birth (PTB). However, previous studies on the
      PTB are inconsistent. Therefore, the aim of this study was to clarify the
      association between IA and PTB and low birth weight (LBW) for first-time mothers.
      A total of 3,684 Southern Chinese women who gave birth for the first time to a
      live singleton infants were recruited between January 2015 and December 2015 in
      the province of Guangdong, China. Univariable and multivariable analyses were
      conducted to determine whether IA was associated with PTB and LBW. Previous IA
      was not associated with increased risks of PTB or LBW, adjusted odds ratios were
      0.80 (95% CI = 0.53 to 1.20) and 0.86 (95% CI = 0.57 to 1.31), respectively.
      Additionally, no significant associations were observed for infants born at
      before 37, before 32, and before 28 gestational weeks. And no significant
      associations were also observed for LBW measuring lower than 2500 grams and also
      measuring lower than 1500 grams. Our study suggested that a previous IA, as
      compared with women who reported no previous IA, does not increase the risk of
      PTB or LBW in subsequent pregnancy for the first-time mothers among Southern
      Chinese women.

PMID- 29599501
TI  - Piercing the dark matter: bioinformatics of long-range sequencing and mapping.
AB  - Several new genomics technologies have become available that offer long-read
      sequencing or long-range mapping with higher throughput and higher resolution
      analysis than ever before. These long-range technologies are rapidly advancing
      the field with improved reference genomes, more comprehensive variant
      identification and more complete views of transcriptomes and epigenomes. However,
      they also require new bioinformatics approaches to take full advantage of their
      unique characteristics while overcoming their complex errors and modalities.
      Here, we discuss several of the most important applications of the new
      technologies, focusing on both the currently available bioinformatics tools and
      opportunities for future research.

PMID- 29599502
TI  - Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia
      Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase.
AB  - Influenza subtypes such as H7 have pandemic potential since they are able to
      infect humans with severe consequences, as evidenced by the ongoing H7N9
      infections in China that began in 2013. The diversity of H7 viruses calls for a
      broadly cross-protective vaccine for protection. We describe the construction of
      recombinant modified vaccinia virus Ankara (MVA) vectors expressing the
      hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both
      Eurasian and North American H7 lineages - A/mallard/Netherlands/12/2000 (H7N3),
      A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). These vectors were
      evaluated for immunogenicity and protective efficacy against H7N3 virus in a
      murine model of intranasal challenge. High levels of H7-, N3-, and N9-specific
      antibodies, including neutralizing antibodies, were induced by the MVA-HA and MVA
      NA vectors. Mice vaccinated with MVA vectors expressing any of the H7 antigens
      were protected, suggesting cross-protection among H7 viruses. In addition, MVA
      vectors expressing N3 but not N9 elicited protection against H7N3 virus
      challenge. Similar outcomes were obtained when immune sera from MVA vector
      immunized mice were passively transferred to naive mice prior to challenge with
      the H7N3 virus. The results support the further development of an MVA vector
      platform as a candidate vaccine for influenza strains with pandemic potential.

PMID- 29599504
TI  - Left main coronary artery disease: pathophysiology, diagnosis, and treatment.
AB  - The advent of coronary angiography in the 1960s allowed for the risk
      stratification of patients with stable angina. Patients with unprotected left
      main coronary artery disease have an increased risk of death related to the large
      amount of myocardium supplied by this vessel. Although coronary angiography
      remains the preferred imaging modality for the evaluation of left main coronary
      artery stenosis, this technique has important limitations. Angiograms of the left
      main coronary artery segment can be difficult to interpret, and almost one-third
      of patients can be misclassified when fractional flow reserve is used as the
      reference. In patients with clinically significant unprotected left main coronary
      artery disease, surgical revascularization was shown to improve survival compared
      with medical therapy and has been regarded as the treatment of choice for
      unprotected left main coronary artery disease. Two large-scale clinical trials
      published in 2016 support the usefulness of catheter-based revascularization in
      selected patients with unprotected left main coronary artery disease. In this
      Review, we describe the pathophysiology of unprotected left main coronary artery
      disease, discuss diagnostic approaches in light of new noninvasive and invasive
      imaging techniques, and detail risk stratification models to aid the Heart Team
      in the decision-making process for determining the best revascularization
      strategy for these patients.

PMID- 29599503
TI  - Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive
      mouse embryonic stem cells.
AB  - Nitric oxide (NO) synthesis is a late event during differentiation of mouse
      embryonic stem cells (mESC) and occurs after release from serum and leukemia
      inhibitory factor (LIF). Here we show that after release from pluripotency, a
      subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial
      nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO
      positive subpopulation (ESNO+) expresses mesendodermal markers and is more
      efficient in the generation of cardiovascular precursors than eNOS/NO-negative
      cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S
      nitrosylation, which reduces association of Hdac2 with the transcriptional
      repression factor Zeb1, allowing mesendodermal gene expression. In conclusion,
      our results suggest that the interaction between Zeb1, Hdac2, and eNOS is
      required for early mesendodermal differentiation of naive mESC.

PMID- 29599505
TI  - Ocean convection linked to the recent ice edge retreat along east Greenland.
AB  - Warm subtropical-origin Atlantic water flows northward across the Greenland
      Scotland Ridge into the Nordic Seas, where it relinquishes heat to the atmosphere
      and gradually transforms into dense Atlantic-origin water. Returning southward
      along east Greenland, this water mass is situated beneath a layer of cold, fresh
      surface water and sea ice. Here we show, using measurements from autonomous ocean
      gliders, that the Atlantic-origin water was re-ventilated while transiting the
      western Iceland Sea during winter. This re-ventilation is a recent phenomenon
      made possible by the retreat of the ice edge toward Greenland. The fresh surface
      layer that characterises this region in summer is diverted onto the Greenland
      shelf by enhanced onshore Ekman transport induced by stronger northerly winds in
      fall and winter. Severe heat loss from the ocean offshore of the ice edge
      subsequently triggers convection, which further transforms the Atlantic-origin
      water. This re-ventilation is a counterintuitive occurrence in a warming climate,
      and highlights the difficulties inherent in predicting the behaviour of the
      complex coupled climate system.

PMID- 29599506
TI  - 3.4 million real-world learning management system logins reveal the majority of
      students experience social jet lag correlated with decreased performance.
AB  - Misalignments between endogenous circadian rhythms and the built environment
      (i.e., social jet lag, SJL) result in learning and attention deficits. Currently,
      there is no way to assess the impact of SJL on learning outcomes of large
      populations as a response to schedule choices, let alone to assess which
      individuals are most negatively impacted by these choices. We analyzed two years
      of learning management system login events for 14,894 Northeastern Illinois
      University (NEIU) students to investigate the capacity of such systems as tools
      for mapping the impact of SJL over large populations while maintaining the
      ability to generate insights about individuals. Personal daily activity profiles
      were validated against known biological timing effects, and revealed a majority
      of students experience more than 30 minutes of SJL on average, with greater
      amplitude correlating strongly with a significant decrease in academic
      performance, especially in people with later apparent chronotypes. Our findings
      demonstrate that online records can be used to map individual- and population
      level SJL, allow deep mining for patterns across demographics, and could guide
      schedule choices in an effort to minimize SJL's negative impact on learning
      outcomes.

PMID- 29599507
TI  - Head tracking extends local active control of broadband sound to higher
      frequencies.
AB  - Local active sound control systems provide useful reductions in noise within a
      zone of quiet which only extends to about one tenth of an acoustic wavelength. If
      active control is required above a few hundred hertz, this generally limits the
      movement of a listener to unrealistically small changes in head position. We
      describe a local active sound control system using a fixed array of monitoring
      microphones, in which the pressures at the ear positions are estimated from these
      microphone signals using head position information from an optical head tracker.
      These signals are then actively controlled to give robust attenuation at the ear
      positions, even as the listener moves their head. Feedforward control provides
      selective attenuation of noise and broadband attenuation of around 20 dB is
      measured up to excitation frequencies of 1 kHz under favourable conditions, with
      head tracking achieved in a few seconds. The active control performance is thus
      comparable with that achieved with active headphones, but without the listener
      having anything attached to their head.

PMID- 29599508
TI  - The association between red blood cell transfusion and outcomes in patients with
      upper gastrointestinal bleeding.
AB  - BACKGROUND: The benefits of transfusion for acute upper gastrointestinal bleeding
      (UGIB) have not been well established; however, previous studies suggest that
      transfusion is associated with adverse outcomes. We performed an observational
      study using a 10-year database to analyze the association between red blood cell
      (RBC) transfusion and outcomes in patients with UGIB in the emergency department
      (ED). METHOD AND FINDINGS: All adult patients with UGIB were identified through
      diagnostic codes. Hospital mortality was the primary outcome; further bleeding
      was the secondary outcome. Logistic regression, propensity analyses, and
      conditional logistic regression were performed to determine factors associated
      with outcomes. Of 59,188 enrolled patients, 31.6% (n = 18,705) received RBC
      transfusions within 24 h following presentation to the ED. Hospital mortality was
      noted in 3.9 and 10.6% of the patients in the non-RBC transfusion and RBC
      transfusion groups, respectively (P < 0.001). RBC transfusion was associated with
      increased mortality risk (unadjusted odds ratio (OR) 2.95, 95% confidence
      interval (CI) 2.75-3.16; P < 0.001) among all patients and in the propensity
      matched cohort (unadjusted OR 1.55, 95% CI 1.39-1.72; P < 0.001). Further
      bleeding was noted in 5.6 and 33.8% of the patients in the non-RBC transfusion
      and RBC transfusion groups, respectively (P < 0.001). RBC transfusion was
      associated with increased risk of further bleeding (unadjusted OR 8.60, 95% CI
      8.16-9.06; P < 0.001) among all patients and in the propensity-matched cohort
      (unadjusted OR 2.58, 95% CI 2.37-2.79; P < 0.001). CONCLUSION: RBC transfusion
      was significantly associated with increased rates of hospital mortality and
      further bleeding in patients with UGIB. Although our findings have strengths,
      these results are not generalizable to all patients presenting with UGIB,
      especially patients presenting with exsanguinating bleeding. Additional
      prospective trials to guide optimal transfusion strategies in UGIB patients are
      needed.

PMID- 29599509
TI  - Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic
      stem cell transplantation.
AB  - Matching classical HLA alleles between donor and recipient is an important factor
      in avoiding adverse immunological effects in HSCT. Siblings with no differences
      in HLA alleles, either due to identical-by-state or identical-by-descent status,
      are considered to be optimal donors. We carried out a retrospective genomic
      sequence and SNP analysis of 336 fully HLA-A, -B, -DRB1 matched and 14 partially
      HLA-matched sibling HSCT pairs to determine the level of undetected mismatching
      within the MHC segment as well as to map their recombination sites. The genomic
      sequence of 34 genes locating in the MHC region revealed allelic mismatching at 1
      to 8 additional genes in partially HLA-matched pairs. Also, fully matched pairs
      were found to have mismatching either at HLA-DPB1 or at non-HLA region within the
      MHC segment. Altogether, 3.9% of fully HLA-matched HSCT pairs had large genomic
      mismatching in the MHC segment. Recombination sites mapped to certain restricted
      locations. The number of mismatched nucleotides correlated with the risk of GvHD
      supporting the central role of full HLA matching in HSCT. High-density genome
      analysis revealed that fully HLA-matched siblings may not have identical MHC
      segments and even single allelic mismatching at any classical HLA gene often
      implies larger genomic differences along MHC.

PMID- 29599510
TI  - Nitrogen uptake kinetics and saltmarsh plant responses to global change.
AB  - Coastal wetlands are important carbon sinks globally, but their ability to store
      carbon hinges on their nitrogen (N) supply and N uptake dynamics of dominant
      plant species. In terrestrial ecosystems, uptake of nitrate (NO3-) and ammonium
      (NH4+) through roots can strongly influence N acquisition rates and their
      responses to environmental factors such as rising atmospheric CO2 and
      eutrophication. We examined the 15N uptake kinetics of three dominant plant
      species in North American coastal wetlands (Spartina patens, C4 grass; Phragmites
      australis, C3 grass; Schoenoplectus americanus, C3 sedge) under ambient and
      elevated CO2 conditions. We further related our results to the productivity
      response of these species in two long-term field experiments. S. patens had the
      greatest uptake rates for NO3- and NH4+ under ambient conditions, suggesting that
      N uptake kinetics may underlie its strong productivity response to N in the
      field. Elevated CO2 increased NH4+ and NO3- uptake rates for S. patens, but had
      negative effects on NO3- uptake rates in P. australis and no effects on S.
      americanus. We suggest that N uptake kinetics may explain differences in plant
      community composition in coastal wetlands and that CO2-induced shifts, in
      combination with N proliferation, could alter ecosystem-scale productivity
      patterns of saltmarshes globally.

PMID- 29599511
TI  - A Mathematical Model for the Sounds Produced by Knuckle Cracking.
AB  - The articular release of the metacarpophalangeal joint produces a typical
      cracking sound, resulting in what is commonly referred to as the cracking of
      knuckles. Despite over sixty years of research, the source of the knuckle
      cracking sound continues to be debated due to inconclusive experimental evidence
      as a result of limitations in the temporal resolution of non-invasive
      physiological imaging techniques. To support the available experimental data and
      shed light onto the source of the cracking sound, we have developed a
      mathematical model of the events leading to the generation of the sound. The
      model resolves the dynamics of a collapsing cavitation bubble in the synovial
      fluid inside a metacarpophalangeal joint during an articular release. The
      acoustic signature from the resulting bubble dynamics is shown to be consistent
      in both magnitude and dominant frequency with experimental measurements in the
      literature and with our own experiments, thus lending support for cavitation
      bubble collapse as the source of the cracking sound. Finally, the model also
      shows that only a partial collapse of the bubble is needed to replicate the
      experimentally observed acoustic spectra, thus allowing for bubbles to persist
      following the generation of sound as has been reported in recent experiments.

PMID- 29599512
TI  - Population genetic evidence for positive and purifying selection acting at the
      human IFN-gamma locus in Africa.
AB  - Despite its critical role in the defense against microbial infection and tumor
      development, little is known about the range of nucleotide and haplotype
      variation at IFN-gamma, or the evolutionary forces that have shaped patterns of
      diversity at this locus. To address this gap in knowledge, we examined sequence
      data from the IFN-gamma gene in 1461 individuals from 15 worldwide populations.
      Our analyses uncovered novel patterns of variation in distinct African
      populations, including an excess of high frequency-derived alleles, unusually
      long haplotype structure surrounding the IFN-gamma gene, and a "star-like"
      genealogy of African-specific haplotypes carrying variants previously associated
      with infectious disease. We also inferred a deep time to coalescence of variation
      at IFN-gamma (~ 0.8 million years ago) and ancient ages for common polymorphisms
      predating the evolution of modern humans. Taken together, these results are
      congruent with a model of positive selection on standing variation in African
      populations. Furthermore, we inferred that common variants in intron 3 of IFN
      gamma are the likely targets of selection. In addition, we observed a paucity of
      non-synonymous substitutions relative to synonymous changes in the exons of IFN
      gamma in African and non-African populations, suggestive of strong purifying
      selection. Therefore, we contend that positive and purifying selection have
      influenced levels of diversity in different regions of IFN-gamma, implying that
      these distinct genic regions are, or have been, functionally important. Overall,
      this study provides additional insights into the evolutionary events that have
      contributed to the frequency and distribution of alleles having a role in human
      health and disease.

PMID- 29599513
TI  - Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of
      arthritis.
AB  - Studies have identified abnormalities in the microbiota of patients with
      arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal
      microbial transplantation from children with spondyloarthritis and controls to
      germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received
      patient vs. control microbiota. Principal coordinates analysis revealed
      incomplete uptake of the human microbiota with over-representation of two genera
      (Bacteroides and Akkermansia) among the transplanted mice. The microbiota
      predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of
      Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p =
      0.078) directly correlated with ankle swelling. Addition of Akkermansia
      muciniphila to Altered Schaedler's Flora (ASF) resulted in small but
      statistically significant increased ankle swelling as compared to mice that
      received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did
      addition of A. muciniphila cultures to transplanted human microbiota as compared
      to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5
      vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an
      association between A. muciniphila and arthritis.

PMID- 29599514
TI  - Human IL12RB1 expression is allele-biased and produces a novel IL12 response
      regulator.
AB  - Human IL12RB1 is an autosomal gene that is essential for mycobacterial disease
      resistance and T cell differentiation. Using primary human tissue and PBMCs, we
      demonstrate that lung and T cell IL12RB1 expression is allele-biased, and the
      extent to which cells express one IL12RB1 allele is unaffected by activation.
      Furthermore following its expression the IL12RB1 pre-mRNA is processed into
      either IL12RB1 Isoform 1 (IL12Rbeta1, a positive regulator of IL12
      responsiveness) or IL12RB1 Isoform 2 (a protein of heretofore unknown function).
      T cells choice to process pre-mRNA into Isoform 1 or Isoform 2 is controlled by
      intragenic competition of IL12RB1 exon 9-10 splicing with IL12RB1 exon 9b
      splicing, as well as an IL12RB1 exon 9b-associated polyadenylation site.
      Heterogeneous nuclear ribonucleoprotein H (hnRNP H) binds near the regulated
      polyadenylation site, but is not required for exon 9b polyadenylation. Finally,
      microRNA-mediated knockdown experiments demonstrated that IL12RB1 Isoform 2
      promotes T cell IL12 responses. Collectively, our data support a model wherein
      tissue expression of human IL12RB1 is allele-biased and produces an hnRNP H-bound
      pre-mRNA, the processing of which generates a novel IL12 response regulator.

PMID- 29599515
TI  - Src signaling in a low-complexity unicellular kinome.
AB  - Creolimax fragrantissima is a member of the ichthyosporean clade, the earliest
      branching holozoan lineage. The kinome of Creolimax is markedly reduced as
      compared to those of metazoans. In particular, Creolimax possesses a single non
      receptor tyrosine kinase: CfrSrc, the homolog of c-Src kinase. CfrSrc is an
      active tyrosine kinase, and it is expressed throughout the lifecycle of
      Creolimax. In animal cells, the regulatory mechanism for Src involves tyrosine
      phosphorylation at a C-terminal site by Csk kinase. The lack of Csk in Creolimax
      suggests that a different mode of negative regulation must exist for CfrSrc. We
      demonstrate that CfrPTP-3, one of the 7 tyrosine-specific phosphatases (PTPs) in
      Creolimax, suppresses CfrSrc activity in vitro and in vivo. Transcript levels of
      CfrPTP-3 and two other PTPs are significantly higher than that of CfrSrc in the
      motile amoeboid and sessile multinucleate stages of the Creolimax life cycle.
      Thus, in the context of a highly reduced kinome, a pre-existing PTP may have been
      co-opted for the role of Src regulation. Creolimax represents a unique model
      system to study the adaptation of tyrosine kinase signaling and regulatory
      mechanisms.

PMID- 29599516
TI  - Enterobacter bugandensis: a novel enterobacterial species associated with severe
      clinical infection.
AB  - Nosocomial pathogens can cause life-threatening infections in neonates and
      immunocompromised patients. E. bugandensis (EB-247) is a recently described
      species of Enterobacter, associated with neonatal sepsis. Here we demonstrate
      that the extended spectrum beta-lactam (ESBL) producing isolate EB-247 is highly
      virulent in both Galleria mellonella and mouse models of infection. Infection
      studies in a streptomycin-treated mouse model showed that EB-247 is as efficient
      as Salmonella Typhimurium in inducing systemic infection and release of
      proinflammatory cytokines. Sequencing and analysis of the complete genome and
      plasmid revealed that virulence properties are associated with the chromosome,
      while antibiotic-resistance genes are exclusively present on a 299 kb IncHI
      plasmid. EB-247 grew in high concentrations of human serum indicating septicemic
      potential. Using whole genome-based transcriptome analysis we found 7% of the
      genome was mobilized for growth in serum. Upregulated genes include those
      involved in the iron uptake and storage as well as metabolism. The lasso peptide
      microcin J25 (MccJ25), an inhibitor of iron-uptake and RNA polymerase activity,
      inhibited EB-247 growth. Our studies indicate that Enterobacter bugandensis is a
      highly pathogenic species of the genus Enterobacter. Further studies on the
      colonization and virulence potential of E. bugandensis and its association with
      septicemic infection is now warranted.

PMID- 29599517
TI  - Increasing prosthetic foot energy return affects whole-body mechanics during
      walking on level ground and slopes.
AB  - Prosthetic feet are designed to store energy during early stance and then release
      a portion of that energy during late stance. The usefulness of providing more
      energy return depends on whether or not that energy transfers up the lower limb
      to aid in whole body propulsion. This research examined how increasing prosthetic
      foot energy return affected walking mechanics across various slopes. Five people
      with a uni-lateral transtibial amputation walked on an instrumented treadmill at
      1.1 m/s for three conditions (level ground, +7.5 degrees , -7.5 degrees ) while
      wearing a prosthetic foot with a novel linkage system and a traditional energy
      storage and return foot. The novel foot demonstrated greater range of motion (p =
      0.0012), and returned more energy (p = 0.023) compared to the traditional foot.
      The increased energy correlated with an increase in center of mass (CoM) energy
      change during propulsion from the prosthetic limb (p = 0.012), and the increased
      prosthetic limb propulsion correlated to a decrease in CoM energy change (i.e.,
      collision) on the sound limb (p < 0.001). These data indicate that this novel
      foot was able to return more energy than a traditional prosthetic foot and that
      this additional energy was used to increase whole body propulsion.

PMID- 29599518
TI  - Psychological outcomes and surgical decisions after genetic testing in women
      newly diagnosed with breast cancer with and without a family history.
AB  - In patients with early breast cancer, personal and tumour characteristics other
      than family history are increasingly used to prompt genetic testing to guide
      women's cancer management (treatment-focused genetic testing, 'TFGT'). Women
      without a known strong family history of breast and/or ovarian may be more
      vulnerable to psychological sequelae arising from TFGT. We compared the impact of
      TFGT in women with (FH+) and without (FH-) a strong family history on
      psychological adjustment and surgical decisions. Women aged <50 years with high
      risk features were offered TFGT before definitive breast cancer surgery and
      completed self-report questionnaires at four time points over 12 months. All 128
      women opted for TFGT. TFGT identified 18 carriers of a disease-causing variant
      (50.0% FH+) and 110 non-carriers (59.1% FH+). There were no differences based on
      family history in bilateral mastectomy (BM) uptake, p = .190, or uptake of risk
      reducing bilateral salpingo-oophorectomy (RRBSO), p = .093. FH- women had lower
      decreases in anxiety a year after diagnosis, p = .011, and regret regarding their
      decision whether to undergo BM, p = .022, or RRBSO, p = .016 than FH + women. FH-
      carriers reported significantly higher regret regarding their TFGT choice (p =
      .024) and test-related distress (p = .012) than FH + carriers, but this
      regret/distress could not be attributed to a concern regarding a possible worse
      prognosis. These findings indicate that FH- women may require additional
      counselling to facilitate informed decisions. Carriers without a family history
      may require additional follow-up counselling to facilitate psychological
      adjustment to their positive variant results, extra support in making surgical
      decisions, and counselling about how best to communicate results to family
      members.

PMID- 29599519
TI  - Cultivation and genomics of the first freshwater SAR11 (LD12) isolate.
AB  - Evolutionary transitions between fresh and salt water happen infrequently among
      bacterioplankton. Within the ubiquitous and highly abundant heterotrophic
      Alphaproteobacteria order Pelagibacterales (SAR11), most members live in marine
      habitats, but the LD12 subclade has evolved as a unique freshwater lineage. LD12
      cells occur as some of the most dominant freshwater bacterioplankton, yet this
      group has remained elusive to cultivation, hampering a more thorough
      understanding of its biology. Here, we report the first successful isolation of
      an LD12 representative, strain LSUCC0530, using high-throughput dilution-to
      extinction cultivation methods, and its complete genome sequence. Growth
      experiments corroborate ecological data suggesting active populations of LD12 in
      brackish water up to salinities of ~5. LSUCC0530 has the smallest closed genome
      thus far reported for a SAR11 strain (1.16 Mbp). The genome affirms many previous
      metabolic predictions from cultivation-independent analyses, like a complete
      Embden-Meyerhof-Parnas glycolysis pathway, but also provides novel insights, such
      as the first isocitrate dehydrogenase in LD12, a likely homologous recombination
      of malate synthase from outside of the SAR11 clade, and analogous substitutions
      of ion transporters with others that occur throughout the rest of the SAR11
      clade. Growth data support metagenomic recruitment results suggesting temperature
      based ecotype diversification within LD12. Key gene losses for osmolyte uptake
      provide a succinct hypothesis for the evolutionary transition of LD12 from salt
      to freshwater. For strain LSUCC0530, we propose the provisional nomenclature
      Candidatus fonsibacter ubiquis.

PMID- 29599520
TI  - Short-term dynamics and interactions of marine protist communities during the
      spring-summer transition.
AB  - We examined the short-term variability, by daily to weekly sampling, of protist
      assemblages from March to July in surface water of the San Pedro Ocean Time
      series station (eastern North Pacific), by V4 Illumina sequencing of the 18S rRNA
      gene. The sampling period encompassed a spring bloom followed by progression to
      summer conditions. Several protistan taxa displayed sharp increases and declines,
      with whole community Bray-Curtis dissimilarities of adjacent days being 66% in
      March and 40% in May. High initial abundance of parasitic Cercozoa Cryothecomonas
      longipes and Protaspis grandis coincided with a precipitous decline of blooming
      Pseudo-nitzschia diatoms, possibly suggesting their massive infection by these
      parasites; these cercozoans were hardly detectable afterwards. Canonical
      correspondence analysis indicated a limited predictability of community
      variability from environmental factors. This indicates that other factors are
      relevant in explaining changes in protist community composition at short temporal
      scales, such as interspecific relationships, stochastic processes, mixing with
      adjacent water, or advection of patches with different protist communities.
      Association network analysis revealed that interactions between the many
      parasitic OTUs and other taxa were overwhelmingly positive and suggest that
      although sometimes parasites may cause a crash of host populations, they may
      often follow their hosts and do not regularly cause enough mortality to
      potentially create negative correlations at the daily to weekly time scales we
      studied.

PMID- 29599521
TI  - Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus
      aureus lineages: potential role of flimsy antibiotic exposure.
AB  - Community-acquired (CA)- as opposed to hospital acquired- methicillin-resistant
      Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To
      determine which factors, including selective antibiotic pressure, govern the
      expansion of two major lineages of CA-MRSA, namely "USA300" in Northern America
      and "European ST80" in North Africa, Europe and Middle-East, we explored
      virulence factor expression, and fitness levels with or without antibiotics. The
      sampled strains were collected in a temporal window representing various steps of
      the epidemics, reflecting predicted changes in effective population size as
      inferred from whole-genome analysis. In addition to slight variations in
      virulence factor expression and biofilm production that might influence the
      ecological niches of theses lineages, competitive fitness experiments revealed
      that the biological cost of resistance to methicillin, fusidic acid and
      fluoroquinolones is totally reversed in the presence of trace amount of
      antibiotics. Our results suggest that low-level antibiotics exposure in human and
      animal environments contributed to the expansion of both European ST80 and USA300
      lineages in community settings. This surge was likely driven by antibiotic
      (ab)use promoting the accumulation of antibiotics as environmental pollutants.
      The current results provide a novel link between effective population size
      increase of a pathogen and a selective advantage conferred by antibiotic
      resistance.

PMID- 29599522
TI  - Syntrophic pathways for microbial mercury methylation.
AB  - Exposure to dietary sources of methylmercury (MeHg) is the focus of public health
      concerns with environmental mercury (Hg) contamination. MeHg is formed in anoxic
      environments by anaerobic microorganisms. This process has been studied mostly
      with single-species culture incubations, although the relevance of such studies
      to Hg(II)-methylation in situ is limited because microbial activities in the
      environment are critically modulated by interactions among microbial functional
      groups. Here we describe experiments in which Hg(II)-methylation was examined
      within the context of various microbial syntrophies. We show enhanced Hg(II)
      methylation under conditions that established syntrophy by interspecies hydrogen
      and acetate transfer. Relative to activity of monocultures, interactions of
      Hg(II) methylating sulfate-reducing bacteria with a methanogen stimulated
      potential Hg(II)-methylation rates 2-fold to 9-fold, and with Syntrophobacter sp.
      1.7-fold to 1.8-fold; those of a Hg(II) methylating Syntrophobacter sp. with a
      methanogen increased Hg(II)-methylation 2-fold. Under sulfate-depleted
      conditions, higher Hg(II)-methylation rates in the syntrophic incubations
      corresponded to higher free energy yields (DeltaG degrees ') than in the
      monocultures. Based on energetic considerations, we therefore propose that
      syntrophic microbial interactions are likely a major source of MeHg in sulfate-
      and iron-limited anoxic environments while in sulfate-replete environments, MeHg
      formation via sulfate reduction dominates.

PMID- 29599523
TI  - Grazer-induced transcriptomic and metabolomic response of the chain-forming
      diatom Skeletonema marinoi.
AB  - Diatoms and copepods are main actors in marine food webs. The prey-predator
      interactions between them affect bloom dynamics, shape marine ecosystems and
      impact the energy transfer to higher trophic levels. Recently it has been
      demonstrated that the presence of grazers may affect the diatom prey beyond the
      direct effect of grazing. Here, we investigated the response of the chain-forming
      centric diatom Skeletonema marinoi to grazer cues, including changes in
      morphology, gene expression and metabolic profile. S. marinoi cells were
      incubated with Calanus finmarchicus or with Centropages typicus and in both cases
      responded by reducing the chain length, whereas changes in gene expression
      indicated an activation of stress response, changes in the lipid and nitrogen
      metabolism, in cell cycle regulation and in frustule formation. Transcripts
      linked to G protein-coupled receptors and to nitric oxide synthesis were
      differentially expressed suggesting involvement of these signalling transduction
      pathways in the response. Downregulation of a lipoxygenase in the transcriptomic
      data and of its products in the metabolomic data also indicate an involvement of
      oxylipins. Our data contribute to a better understanding of the gene function in
      diatoms, providing information on the nature of genes implicated in the
      interaction with grazers, a crucial process in marine ecosystems.

PMID- 29599524
TI  - Thermophilic endospores associated with migrated thermogenic hydrocarbons in deep
      Gulf of Mexico marine sediments.
AB  - Dormant endospores of thermophilic bacteria (thermospores) can be detected in
      cold marine sediments following high-temperature incubation. Thermospores in the
      cold seabed may be explained by a dispersal history originating in deep biosphere
      oil reservoir habitats where upward migration of petroleum fluids at hydrocarbon
      seeps transports viable cells into the overlying ocean. We assessed this deep-to
      shallow dispersal hypothesis through geochemical and microbiological analyses of
      111 marine sediments from the deep water Eastern Gulf of Mexico. GC-MS and
      fluorescence confirmed the unambiguous presence of thermogenic hydrocarbons in 71
      of these locations, indicating seepage from deeply sourced petroleum in the
      subsurface. Heating each sediment to 50  degrees C followed by 16S rRNA gene
      sequencing revealed several thermospores with a cosmopolitan distribution
      throughout the study area, as well as thermospores that were more geographically
      restricted. Among the thermospores having a more limited distribution, 12 OTUs
      from eight different lineages were repeatedly detected in sediments containing
      thermogenic hydrocarbons. A subset of these were significantly correlated with
      hydrocarbons (p < 0.05) and most closely related to Clostridiales previously
      detected in oil reservoirs from around the world. This provides evidence of
      bacteria in the ocean being dispersed out of oil reservoirs, and suggests that
      specific thermospores may be used as model organisms for studying warm-to-cold
      transmigration in the deep sea.

PMID- 29599525
TI  - A role for the gibberellin pathway in biochar-mediated growth promotion.
AB  - Biochar is a carbon negative soil amendment that can promote crop growth.
      However, the effects of biochar on different plant species and cultivars within a
      species are not well understood, nor is the underlying basis of biochar-mediated
      plant growth promotion. This knowledge is critical for optimal use of biochar and
      for breeding biochar-responsive plants. Here, we investigated the genotype
      specific effects of biochar on two cultivars of Solanum lycopersicum (tomato),
      and two wild relatives of tomato, Solanum pimpinellifolium, and Solanum pennelli,
      in two types of biochar. Biochar promoted shoot growth in all genotypes
      independent of biochar type but had genotype-dependent effects on other plant
      traits. Germination tests, exogenous GA4 application and mutant analysis
      indicated a role for GA in biochar-mediated plant growth promotion. Together, our
      results suggest that biochar promotes growth partially through stimulation of the
      GA pathway.

PMID- 29599526
TI  - (More) women in science.

PMID- 29599527
TI  - The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its
      direct role in nuclear DNA repair.
AB  - EXD2 is a recently identified exonuclease that has been implicated in nuclear
      double-strand break repair. Given our long standing interest in mitochondrial DNA
      maintenance and indications that EXD2 could also be a mitochondrial protein we
      sought to determine its cellular localization and possible mitochondrial
      associated functions. Our results show that EXD2 indeed shows mitochondrial
      localization, but, surprisingly, is found predominantly associated with the
      mitochondrial outer-membrane. Gradient purified nuclei show only the faintest
      hint of EXD2 presence while overexpression of the predicted full-length protein
      shows exclusive mitochondrial localization. Importantly, induction of double
      strand DNA breaks via X-irradiation or Zeocin treatment does not support the
      notion that EXD2 re-locates to the nucleus following double-strand breaks and
      thus is unlikely to have a direct role in nuclear DNA repair. Knockdown or
      overexpression of EXD2 affects the cellular distribution of mitochondria. These
      results suggest that the reported defects in nuclear DNA repair following EXD2
      depletion are likely an indirect consequence of altered mitochondrial dynamics
      and/or function.

PMID- 29599528
TI  - Hematopoietic stem cell transplantation using non-cryopreserved peripheral blood
      stem cells graft is effective in multiple myeloma and lymphoma.

PMID- 29599529
TI  - Interbrain cortical synchronization encodes multiple aspects of social
      interactions in monkey pairs.
AB  - While it is well known that the primate brain evolved to cope with complex social
      contingencies, the neurophysiological manifestation of social interactions in
      primates is not well understood. Here, concurrent wireless neuronal ensemble
      recordings from pairs of monkeys were conducted to measure interbrain cortical
      synchronization (ICS) during a whole-body navigation task that involved
      continuous social interaction of two monkeys. One monkey, the passenger, was
      carried in a robotic wheelchair to a food dispenser, while a second monkey, the
      observer, remained stationary, watching the passenger. The two monkeys alternated
      the passenger and the observer roles. Concurrent neuronal ensemble recordings
      from the monkeys' motor cortex and the premotor dorsal area revealed episodic
      occurrence of ICS with probability that depended on the wheelchair kinematics,
      the passenger-observer distance, and the passenger-food distance - the social
      interaction factors previously described in behavioral studies. These results
      suggest that ICS represents specific aspects of primate social interactions.

PMID- 29599530
TI  - Excessive activated T-cell proliferation after anti-CD19 CAR T-cell therapy.
AB  - Excessive activated T-cell proliferation was observed in vivo in one patient
      after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient,
      who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL),
      received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy
      (fludarabine/cyclophosphamide). The lymphocyte count in the peripheral blood (PB)
      increased to 77 * 109/L on day 13 post infusion, and the proportion of CD8+
      actived T cells was 93.06% of the lymphocytes. Then, the patient suffered from
      fever and hypoxaemia. Significant increases in serum cytokine, lactate
      dehydrogenase, aspartate aminotransferase (AST), alanine transaminase (ALT), and
      glutamic-oxalacetic transaminase (gamma-GT) levels were observed. A high
      throughput sequencing analysis for T-cell receptors (TCRs) and whole-genome
      sequencing were used to explore the mechanisms underlying this excessive T-cell
      proliferation. TCR diversity was demonstrated, but no special gene mutation was
      found. The patient was found to be infected with the John Cunningham polyomavirus
      (JCV). It cannot be ruled out the bystander activation pathway induced by JCV
      infections related the excessive activated T-cell proliferation. Although the
      clinical and laboratory data do not fully explain the reason for excessive T-cell
      proliferation after the anti-CD19 CAR T-cell infusion, the risk of this type of
      toxicity should be emphasized. This study was registered at
      www.clinicaltrials.gov as NCT01864889.

PMID- 29599531
TI  - Collaborative hierarchy maintains cooperation in asymmetric games.
AB  - The interplay of social structure and cooperative behavior is under much scrutiny
      lately as behavior in social contexts becomes increasingly relevant for everyday
      life. Earlier experimental work showed that the existence of a social hierarchy,
      earned through competition, was detrimental for the evolution of cooperative
      behaviors. Here, we study the case in which individuals are ranked in a
      hierarchical structure based on their performance in a collective effort by
      having them play a Public Goods Game. In the first treatment, participants are
      ranked according to group earnings while, in the second treatment, their rankings
      are based on individual earnings. Subsequently, participants play asymmetric
      Prisoner's Dilemma games where higher-ranked players gain more than lower ones.
      Our experiments show that there are no detrimental effects of the hierarchy
      formed based on group performance, yet when ranking is assigned individually we
      observe a decrease in cooperation. Our results show that different levels of
      cooperation arise from the fact that subjects are interpreting rankings as a
      reputation which carries information about which subjects were cooperators in the
      previous phase. Our results demonstrate that noting the manner in which a
      hierarchy is established is essential for understanding its effects on
      cooperation.

PMID- 29599532
TI  - [Job satisfaction vs. occupational stress - Quantitative analysis of 3
      organizational units of a public sector institution].
AB  - BACKGROUND: The influence of subjective perception of occupational stress and its
      individual factors on the overall level of job satisfaction was analyzed. The
      respondents were also asked to answer the question of the potential differences
      in terms of variables in managers and non-managers, and in various demographic
      factors. MATERIAL AND METHODS: This article presents the results of a study
      conducted among 5930 people employed in 3 units of the examined public sector
      institution. The research was conducted using computer-assisted web interview
      method. The parameters of the polynomial model of ordered categories were
      estimated. RESULTS: The results showed a statistically significant effect between
      the variables and the differences between the groups of subjects. Analyzes showed
      slight differences between men and women. Employees with a low level of stress
      and high job satisfaction were noted in the oldest group, aged over 55 years, and
      in managers. Low levels of stress and job satisfaction were observed in young
      employees with the shortest period of employment. Among those least satisfied
      with the work and experiencing high levels of stress there were respondents with
      6-15 years of employment in non-managerial positions. While the highest levels of
      stress and high satisfaction were found in people aged 46-55 years, with more
      than 20 years of work experience. CONCLUSIONS: The results of the estimation of
      the polynomial model parameters of ordered categories indicate that the level of
      perceived stress is related to the level of job satisfaction. The lower the level
      of stress and stressors in the workplace, the greater the job satisfaction in the
      surveyed unit. Med Pr 2018;69(3):301-315.

PMID- 29599533
TI  - Conceptions of Good Science in Our Data-Rich World.
AB  - Scientists have been debating for centuries the nature of proper scientific
      methods. Currently, criticisms being thrown at data-intensive science are
      reinvigorating these debates. However, many of these criticisms represent long
      standing conflicts over the role of hypothesis testing in science and not just a
      dispute about the amount of data used. Here, we show that an iterative account of
      scientific methods developed by historians and philosophers of science can help
      make sense of data-intensive scientific practices and suggest more effective ways
      to evaluate this research. We use case studies of Darwin's research on evolution
      by natural selection and modern-day research on macrosystems ecology to
      illustrate this account of scientific methods and the innovative approaches to
      scientific evaluation that it encourages. We point out recent changes in the
      spheres of science funding, publishing, and education that reflect this richer
      account of scientific practice, and we propose additional reforms.

PMID- 29599534
TI  - Harmonizing Biodiversity Conservation and Productivity in the Context of
      Increasing Demands on Landscapes.
AB  - Biodiversity conservation and agricultural production are often seen as mutually
      exclusive objectives. Strategies for reconciling them are intensely debated. We
      argue that harmonization between biodiversity conservation and crop production
      can be improved by increasing our understanding of the underlying relationships
      between them. We provide a general conceptual framework that links biodiversity
      and agricultural production through the separate relationships between land use
      and biodiversity and between land use and production. Hypothesized relationships
      are derived by synthesizing existing empirical and theoretical ecological
      knowledge. The framework suggests nonlinear relationships caused by the
      multifaceted impacts of land use (composition, configuration, and intensity). We
      propose solutions for overcoming the apparently dichotomous aims of maximizing
      either biodiversity conservation or agricultural production and suggest new
      hypotheses that emerge from our proposed framework.

PMID- 29599535
TI  - Prospects for Increasing Sugarcane and Bioethanol Production on Existing Crop
      Area in Brazil.
AB  - This article assesses sugarcane yield gaps (YG) in Brazil to determine the degree
      to which production can be increased without land expansion. In our scenario
      assessments, we evaluated how much of the projected sugarcane demand to 2024 (for
      both sugar and bioethanol) can be satisfied through YG closure. The current
      national average yield is 62% of yield potential estimated for rainfed conditions
      (i.e., a YG of 38%). Continuing the historical rate of yield gain is not
      sufficient to meet the projected demand without an area expansion by 5% and 45%
      for low- and high-demand scenarios, respectively. Closing the exploitable YG to
      80% of potential yield would meet future sugarcane demand, with an 18% reduction
      in sugarcane area for the low-demand scenario or a 13% expansion for the high
      demand scenario. A focus on accelerating yield gains to close current exploitable
      YG is a high priority for meeting future demand while minimizing pressure on
      additional land requirements.

PMID- 29599536
TI  - Critical Uncertainties and Gaps in the Environmental- and Social-Impact
      Assessment of the Proposed Interoceanic Canal through Nicaragua.
AB  - The proposed interoceanic canal will connect the Caribbean Sea with the Pacific
      Ocean, traversing Lake Nicaragua, the major freshwater reservoir in Central
      America. If completed, the canal would be the largest infrastructure-related
      excavation project on Earth. In November 2015, the Nicaraguan government approved
      an environmental and social impact assessment (ESIA) for the canal. A group of
      international experts participated in a workshop organized by the Academy of
      Sciences of Nicaragua to review this ESIA. The group concluded that the ESIA does
      not meet international standards; essential information is lacking regarding the
      potential impacts on the lake, freshwater and marine environments, and
      biodiversity. The ESIA presents an inadequate assessment of natural hazards and
      socioeconomic disruptions. The panel recommends that work on the canal project be
      suspended until an appropriate ESIA is completed. The project should be resumed
      only if it is demonstrated to be economically feasible, environmentally
      acceptable, and socially beneficial.

PMID- 29599537
TI  - The Multitrophic Effects of Climate Change and Glacier Retreat in Mountain
      Rivers.
AB  - Climate change is driving the thinning and retreat of many glaciers globally.
      Reductions of ice-melt inputs to mountain rivers are changing their
      physicochemical characteristics and, in turn, aquatic communities. Glacier-fed
      rivers can serve as model systems for investigations of climate-change effects on
      ecosystems because of their strong atmospheric-cryospheric links, high
      biodiversity of multiple taxonomic groups, and significant conservation interest
      concerning endemic species. From a synthesis of existing knowledge, we develop a
      new conceptual understanding of how reducing glacier cover affects organisms
      spanning multiple trophic groups. Although the response of macroinvertebrates to
      glacier retreat has been well described, we show that there remains a relative
      paucity of information for biofilm, microinvertebrate, and vertebrate taxa.
      Enhanced understanding of whole river food webs will improve the prediction of
      river-ecosystem responses to deglaciation while offering the potential to
      identify and protect a wider range of sensitive and threatened species.

PMID- 29599538
TI  - From Agricultural Benefits to Aviation Safety: Realizing the Potential of
      Continent-Wide Radar Networks.
AB  - Migratory animals provide a multitude of services and disservices-with benefits
      or costs in the order of billions of dollars annually. Monitoring, quantifying,
      and forecasting migrations across continents could assist diverse stakeholders in
      utilizing migrant services, reducing disservices, or mitigating human-wildlife
      conflicts. Radars are powerful tools for such monitoring as they can assess
      directional intensities, such as migration traffic rates, and biomass
      transported. Currently, however, most radar applications are local or small scale
      and therefore substantially limited in their ability to address large-scale
      phenomena. As weather radars are organized into continent-wide networks and also
      detect "biological targets," they could routinely monitor aerial migrations over
      the relevant spatial scales and over the timescales required for detecting
      responses to environmental perturbations. To tap these unexploited resources, a
      concerted effort is needed among diverse fields of expertise and among
      stakeholders to recognize the value of the existing infrastructure and data
      beyond weather forecasting.

PMID- 29599539
TI  - Freshwater Megafauna: Flagships for Freshwater Biodiversity under Threat.
AB  - Freshwater biodiversity is highly threatened and is decreasing more rapidly than
      its terrestrial or marine counterparts; however, freshwaters receive less
      attention and conservation investment than other ecosystems do. The diverse group
      of freshwater megafauna, including iconic species such as sturgeons, river
      dolphins, and turtles, could, if promoted, provide a valuable tool to raise
      awareness and funding for conservation. We found that freshwater megafauna
      inhabit every continent except Antarctica, with South America, Central Africa,
      and South and Southeast Asia being particularly species rich. Freshwater
      megafauna co-occur with up to 93% of mapped overall freshwater biodiversity.
      Fifty-eight percent of the 132 megafauna species included in the study are
      threatened, with 84% of their collective range falling outside of protected
      areas. Of all threatened freshwater species, 83% are found within the megafauna
      range, revealing the megafauna's capacity as flagship and umbrella species for
      fostering freshwater conservation.

PMID- 29599540
TI  - Society Is Ready for a New Kind of Science-Is Academia?

PMID- 29599541
TI  - Grant-Writing Bootcamp: An Intervention to Enhance the Research Capacity of
      Academic Women in STEM.
AB  - Broadening the participation of women in science, technology, engineering, and
      mathematical (STEM) fields is more than a social-justice issue; diversity is
      paramount to a thriving national research agenda. However, women face several
      obstacles to fully actualizing their research potential. Enhancing the research
      capacity and opportunity of women faculty requires purposeful changes in
      university practice. Therefore, we designed an intervention, a grant-writing
      bootcamp informed by self-determination theory (Deci and Ryan 2012), to support
      the participants' feelings of relatedness, autonomy, and competence. Three grant
      writing bootcamps were run over an 18-month period. Using a pre- and post-test
      design over the span of 1 year (and contrasting results with a comparison sample
      who were not part of the intervention) showed that the women participating in the
      grant-writing bootcamp significantly increased the number of external grants
      submitted, the number of proposals led as principal investigator, the number of
      external grants awarded, and the amount of external funding dollars awarded.

PMID- 29599542
TI  - Google Haul Out: Earth Observation Imagery and Digital Aerial Surveys in Coastal
      Wildlife Management and Abundance Estimation.
AB  - As the sampling frequency and resolution of Earth observation imagery increase,
      there are growing opportunities for novel applications in population monitoring.
      New methods are required to apply established analytical approaches to data
      collected from new observation platforms (e.g., satellites and unmanned aerial
      vehicles). Here, we present a method that estimates regional seasonal abundances
      for an understudied and growing population of gray seals (Halichoerus grypus) in
      southeastern Massachusetts, using opportunistic observations in Google Earth
      imagery. Abundance estimates are derived from digital aerial survey counts by
      adapting established correction-based analyses with telemetry behavioral
      observation to quantify survey biases. The result is a first regional
      understanding of gray seal abundance in the northeast US through opportunistic
      Earth observation imagery and repurposed animal telemetry data. As species
      observation data from Earth observation imagery become more ubiquitous, such
      methods provide a robust, adaptable, and cost-effective solution to monitoring
      animal colonies and understanding species abundances.

PMID- 29599543
TI  - Corrigendum: Assessing National Biodiversity Trends for Rocky and Coral Reefs
      through the Integration of Citizen Science and Scientific Monitoring Programs.
AB  - [This corrects the article DOI: 10.1093/biosci/biw180.].

PMID- 29599544
TI  - International Wildlife Law: Understanding and Enhancing Its Role in Conservation.

PMID- 29599545
TI  - Shipbuilding Docks as Experimental Systems for Realistic Assessments of
      Anthropogenic Stressors on Marine Organisms.
AB  - Empirical investigations of the impacts of anthropogenic stressors on marine
      organisms are typically performed under controlled laboratory conditions, onshore
      mesocosms, or via offshore experiments with realistic (but uncontrolled)
      environmental variation. These approaches have merits, but onshore setups are
      generally small sized and fail to recreate natural stressor fields, whereas
      offshore studies are often compromised by confounding factors. We suggest the use
      of flooded shipbuilding docks to allow studying realistic exposure to stressors
      and their impacts on the intra- and interspecific responses of animals.
      Shipbuilding docks permit the careful study of groups of known animals, including
      the evaluation of their behavioral interactions, while enabling full control of
      the stressor and many environmental conditions. We propose that this approach
      could be used for assessing the impacts of prominent anthropogenic stressors,
      including chemicals, ocean warming, and sound. Results from shipbuilding-dock
      studies could allow improved parameterization of predictive models relating to
      the environmental risks and population consequences of anthropogenic stressors.

PMID- 29599546
TI  - Global Biodiversity Threatened by Science Budget Cuts in Brazil.

PMID- 29599547
TI  - The Future of Landscape Conservation.

PMID- 29599550
TI  - Transportation of horses to Japan for slaughter - A reply.

PMID- 29599548
TI  - Worldwide Engagement for Digitizing Biocollections (WeDigBio): The Biocollections
      Community's Citizen-Science Space on the Calendar.
AB  - The digitization of biocollections is a critical task with direct implications
      for the global community who use the data for research and education. Recent
      innovations to involve citizen scientists in digitization increase awareness of
      the value of biodiversity specimens; advance science, technology, engineering,
      and math literacy; and build sustainability for digitization. In support of these
      activities, we launched the first global citizen-science event focused on the
      digitization of biodiversity specimens: Worldwide Engagement for Digitizing
      Biocollections (WeDigBio). During the inaugural 2015 event, 21 sites hosted
      events where citizen scientists transcribed specimen labels via online platforms
      (DigiVol, Les Herbonautes, Notes from Nature, the Smithsonian Institution's
      Transcription Center, and Symbiota). Many citizen scientists also contributed off
      site. In total, thousands of citizen scientists around the world completed over
      50,000 transcription tasks. Here, we present the process of organizing an
      international citizen-science event, an analysis of the event's effectiveness,
      and future directions-content now foundational to the growing WeDigBio event.

PMID- 29599549
TI  - Urban Mind: Using Smartphone Technologies to Investigate the Impact of Nature on
      Mental Well-Being in Real Time.
AB  - Existing evidence on the beneficial effects of nature on mental health comes from
      studies using cross-sectional designs. We developed a smartphone-based tool
      (Urban Mind; www.urbanmind.info) to examine how exposure to natural features
      within the built environment affects mental well-being in real time. The tool was
      used to monitor 108 individuals who completed 3013 assessments over a 1-week
      period. Significant immediate and lagged associations with mental well-being were
      found for several natural features. These associations were stronger in people
      with higher trait impulsivity, a psychological measure of one's tendency to
      behave with little forethought or consideration of the consequences, which is
      indicative of a higher risk of developing mental-health issues. Our investigation
      suggests that the benefits of nature on mental well-being are time-lasting and
      interact with an individual's vulnerability to mental illness. These findings
      have potential implications from the perspectives of global mental health as well
      as urban planning and design.

PMID- 29599551
TI  - CVMA: 70 and going strong.

PMID- 29599552
TI  - Veterinary Medical Ethics.

PMID- 29599553
TI  - Suspected congenital urethral diverticulum in a dog.
AB  - A 2-year-old neutered male dog with a history of urinary incontinence, recurrent
      urinary tract infections, and unilateral cryptorchidism was presented with an
      acute onset of perineal swelling. Urinary contrast studies revealed a urothelial
      lined structure in the perineum. Surgical resection of 80% to 90% of this
      structure, suspected to be a congenital urethral diverticulum, was successful.

PMID- 29599554
TI  - Catastrophic gastric rupture in a horse secondary to psyllium pharmacobezoars.
AB  - A mare was euthanized because of gastric rupture secondary to complete duodenal
      obstruction by 2 bezoars located in the pylorus and proximal duodenum. Infrared
      spectroscopy showed that the bezoars were composed of psyllium. The mare had been
      receiving treatment with a pelleted psyllium product at 4 times the recommended
      dosage. Veterinarians should be aware that treatment of colic in horses with
      pelleted psyllium products could be associated with gastric impaction.

PMID- 29599555
TI  - Case-control study of mineral concentrations of hoof horn tissue derived from
      feedlot cattle with toe tip necrosis syndrome (toe necrosis).
AB  - This study determined whether mineral concentrations in the hooves of cattle with
      toe tip necrosis syndrome (cases) differed from those of cattle dying of all
      other causes (controls). Samples were collected over a 2-year period from 16
      different feedlots and analyzed for 8 minerals [cobalt (Co), copper (Cu), iron
      (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc
      (Zn)]. Mineral concentrations in the hoof wall and solar horn of the same hoof
      were poorly correlated; Se was the most correlated (rho = 0.865; P < 0.001),
      while Mg (rho = 0.465; P < 0.001) and Zn (rho = 0.157; P = 0.053) were the least
      correlated. The cases had significantly lower Mg concentrations in both the hoof
      wall and solar horn tissue compared to the control subjects. For every 10 ppm
      decrease in Mg, the odds of a diagnosis of toe tip necrosis syndrome (TTNS)
      increased by 1.13 times for the hoof wall (P = 0.002) and 1.21 times for solar
      horn (P < 0.001).

PMID- 29599556
TI  - Evaluation of post-operative pain after active desufflation at completion of
      laparoscopy in mares undergoing ovariectomy.
AB  - The cause of transient post-operative pain in a subset of horses undergoing
      laparoscopy is unclear. The objective of this study was to evaluate if residual
      pneumoperitoneum is associated with transient post-operative pain in mares
      undergoing ovariectomy. Thirty-eight mares undergoing routine standing
      laparoscopic ovariectomy were randomly allocated into 2 groups. At the completion
      of laparoscopy, either the abdominal cavity was actively desufflated or the
      cannulas were opened to achieve ambient pressure before incisional closure.
      Assessments were performed for 18 hours after surgery using a validated
      visceral/somatic pain scale for horses. Overall, pain was minimal in both groups
      (median score 2/39) post-surgery. Active desufflation of the pneumoperitoneum at
      the completion of laparoscopy approached statistical significance (P = 0.07) in
      decreasing pain at 12 hours after laparoscopy. However, effects of active
      desuffation were not significant throughout the monitored 18-hour post-surgery
      period. We conclude that the decision to actively desufflate at the completion of
      laparoscopy should be based on surgeon's preference.

PMID- 29599557
TI  - The distribution of animal antimicrobials in British Columbia for over-the
      counter and veterinary sales, 2012 to 2014.
AB  - Canadian Animal Health Institute (CAHI) data are used for provincial, national,
      and international comparisons of Canadian animal antimicrobial use. The
      objectives of this paper were to: i) use CAHI and British Columbia (BC)
      antimicrobial distribution data to group BC antimicrobial sales into the
      following BC retail distribution channels: over-the-counter retail outlets,
      livestock and poultry feed mills, aquaculture feed mills, livestock and poultry
      veterinarians, and companion animal veterinarians; and ii) to validate the CAHI
      BC distribution data and BC's antimicrobial distribution data from 2012 to 2014.
      Annual total antimicrobial distribution and distribution by antimicrobial class
      were presented for each distribution channel. The distribution of medically
      important antimicrobials for production animals was validated, the distribution
      of ionophores was not. A lack of data precluded any attempt to validate the
      distribution of antimicrobials for companion animals. Each distribution channel
      typically experienced substantial fluctuations in total antimicrobial use and use
      by antibiotic class at least once over the 3-year period. The validated data are
      useful for evidence-based analysis of a proposed Canadian policy requiring a
      veterinary prescription for all medically important antimicrobials.

PMID- 29599558
TI  - Short- and long-term outcomes after shoulder excision arthroplasty in 7 small
      breed dogs.
AB  - This study reports short- and long-term clinical outcomes following excision
      arthroplasty in 7 small breed dogs with shoulder pathology. Lameness and pain
      were scored before surgery, and reassessed at short- and long-term follow-ups
      with measurements of range of motion (ROM), scapulo-humeral angles of extension
      (EA) and flexion (FA), and muscle girth (MG) of the operated and contralateral
      limbs. All dogs improved clinically for lameness and pain. Range of motion, EA,
      and FA of the operated limb were not significantly different compared with the
      contralateral limb at short-term follow-up, but ROM and EA were significantly
      decreased at long-term examination. Muscle girth was not significantly different
      than the contralateral limb. Radiographic re-evaluations showed bony
      proliferation around osteotomies without interosseous union in most dogs and all
      owners were satisfied with the surgery outcome. Excision arthroplasty seems to be
      an effective treatment for chronic shoulder pathologies in small dogs. Range of
      motion and EA were decreased and a mild lameness remained present at long-term
      follow-up.

PMID- 29599560
TI  - Veterinary care across Canada: Average provincial fees in 2017.

PMID- 29599559
TI  - Characteristics of parasitic egg shedding over a 1-year period in foals and their
      dams in 2 farms in central Saskatchewan.
AB  - The goals of this study were to report the seasonal shedding patterns of
      strongyle and Parascaris spp. eggs in repeated fecal samples for mares (n = 38)
      and foals (n = 39), and to evaluate the efficacy of ivermectin treatment in mares
      from 2 selected horse breeding farms in central Saskatchewan. Median strongyle
      fecal egg counts (FEC) peaked in July and August in adult horses. The farms
      differed significantly (P = 0.0005) in regard to strongyle shedding categories (<
      200; 200 to 500; and > 500 eggs/g) over time, but for each individual horse (both
      farms combined) these categories did not differ over time (P = 0.13) on samples
      collected in grazing season. When evaluating 3 samples collected fall, summer and
      fall in 2 consecutive grazing seasons, 94% of horses that shed < 200 eggs/g on 2
      initial samples, remained in the same category on the third sample. Mares on each
      farm didn't differ statistically in shedding categories when comparing September
      samples from 2 consecutive years (Farm A: P = 0.56, Farm B: P = 0.06). Peak
      strongyle shedding occurred late fall in the first year of life for foals on Farm
      A, and in July in the second year of life for foals on Farm B. Parascaris spp.
      FEC were greatest in foals <= 6 months of age, with peak observed when foals were
      5 to 6 months old. Ivermectin was 100% effective at reducing strongyle FEC 2
      weeks after treatment in adult horses. Horses in Saskatchewan had relatively high
      strongyle shedding levels, which were significantly different between the farms,
      and high prevalence of Oxyuris equi. Strongyle shedding consistency was observed
      for FECs collected from mares in grazing season (July to September).

PMID- 29599561
TI  - Concomitant feline immunodeficiency virus (FIV) and Mycoplasma haemofelis in a
      barn cat.
AB  - A 5-year-old male barn cat was presented with lethargy and excessive bleeding
      following castration. The patient developed hemolytic anemia and diagnostic tests
      revealed infection with feline immunodeficiency virus and Mycoplasma haemofelis.
      This case serves as a reminder of the importance of testing for infectious
      diseases and educating owners on feline infectious disease prevention and
      management.

PMID- 29599562
TI  - Atopic dermatitis in cats.

PMID- 29599563
TI  - Change is needed to correct the lack of veterinary dental education at the
      undergraduate level.

PMID- 29599564
TI  - Diagnostic Ophthalmology.

PMID- 29599565
TI  - Some relevant parameters for assessing fire hazards of combustible mine materials
      using laboratory scale experiments.
AB  - When combustible materials ignite and burn, the potential for fire growth and
      flame spread represents an obvious hazard, but during these processes of ignition
      and flaming, other life hazards present themselves and should be included to
      ensure an effective overall analysis of the relevant fire hazards. In particular,
      the gases and smoke produced both during the smoldering stages of fires leading
      to ignition and during the advanced flaming stages of a developing fire serve to
      contaminate the surrounding atmosphere, potentially producing elevated levels of
      toxicity and high levels of smoke obscuration that render the environment
      untenable. In underground mines, these hazards may be exacerbated by the existing
      forced ventilation that can carry the gases and smoke to locations far-removed
      from the fire location. Clearly, materials that require high temperatures (above
      1400 K) and that exhibit low mass loss during thermal decomposition, or that
      require high heat fluxes or heat transfer rates to ignite represent less of a
      hazard than materials that decompose at low temperatures or ignite at low levels
      of heat flux. In order to define and quantify some possible parameters that can
      be used to assess these hazards, small-scale laboratory experiments were
      conducted in a number of configurations to measure: 1) the toxic gases and smoke
      produced both during non-flaming and flaming combustion; 2) mass loss rates as a
      function of temperature to determine ease of thermal decomposition; and 3) mass
      loss rates and times to ignition as a function of incident heat flux. This paper
      describes the experiments that were conducted, their results, and the development
      of a set of parameters that could possibly be used to assess the overall fire
      hazard of combustible materials using small scale laboratory experiments.

PMID- 29599566
TI  - Show Yourself, Asparaginase: An Enzymatic Reaction Explained through a Hands-On
      Interactive Activity.
AB  - Determining the catalytic activity of an enzyme can be the perfect method for its
      identification, for example during purification procedures or for isolation
      purposes. Herein, we used a pharmaceutically relevant protein to bring the
      concept of enzymatic activity to the classroom. We designed a hands-on
      interactive activity in which a medically relevant enzyme, asparaginase, was
      distinguished from a nonenzymatic protein based on its specific enzymatic
      activity. The experiment was carried out in the classroom, designed to impact
      different educational levels from elementary to high school. Our main purposes
      were to promote the emerging field of protein-based drugs as a source of
      scientific careers in bionanotechnology and to show the students an image of a
      "scientist" as that of a common and educated person working in an exciting
      profession. In addition of being inexpensive, this activity proved to be
      adaptable for various educational levels and can be easily implemented in
      different scenarios, for example, scientific fairs, some schools, and so forth.

PMID- 29599567
TI  - Evaluation of Blob Theory for the Diffusion of DNA in Nanochannels.
AB  - We have measured the diffusivity of lambda-DNA molecules in approximately square
      nanochannels with effective sizes ranging from 117 nm to 260 nm at moderate ionic
      strength. The experimental results do not agree with the non-draining scaling
      predicted by blob theory. Rather, the data are consistent with the predictions of
      previous simulations of the Kirkwood diffusivity of a discrete wormlike chain
      model, without the need for any fitting parameters.

PMID- 29599568
TI  - Assessing the Accuracy of Multi-Temporal Built-Up Land Layers across Rural-Urban
      Trajectories in the United States.
AB  - Global data on settlements, built-up land and population distributions are
      becoming increasingly available and represent important inputs to a better
      understanding of key demographic processes such as urbanization and interactions
      between human and natural systems over time. One persistent drawback that
      prevents user communities from effectively and objectively using these data
      products more broadly, is the absence of thorough and transparent validation
      studies. This study develops a validation framework for accuracy assessment of
      multi-temporal built-up land layers using integrated public parcel and building
      records as validation data. The framework is based on measures derived from
      confusion matrices and incorporates a sensitivity analysis for potential spatial
      offsets between validation and test data as well as tests for the effects of
      varying criteria of the abstract term built-up land on accuracy measures.
      Furthermore, the framework allows for accuracy assessments by strata of built-up
      density, which provides important insights on the relationship between
      classification accuracy and development intensity to better instruct and educate
      user communities on quality aspects that might be relevant to different purposes.
      We use data from the newly-released Global Human Settlement Layer (GHSL), for
      four epochs since 1975 and at fine spatial resolution (38m), in the United States
      for a demonstration of the framework. The results show very encouraging accuracy
      measures that vary across study areas, generally improve over time but show very
      distinct patterns across the rural-urban trajectories. Areas of higher
      development intensity are very accurately classified and highly reliable. Rural
      areas show low degrees of accuracy, which could be affected by misalignment
      between the reference data and the data under test in areas where built-up land
      is scattered and rare. However, a regression analysis, which examines how well
      GHSL can estimate built-up land using spatially aggregated analytical units,
      indicates that classification error is mainly of thematic nature. Thus, caution
      should be taken in using the data product in rural regions. The results can be
      useful in further improving classification procedures to create measures of the
      built environment. The validation framework can be extended to data-poor regions
      of the world using map data and Volunteered Geographic Information.

PMID- 29599569
TI  - Hispanic Concentrated Poverty in Traditional and New Destinations, 2010-2014.
AB  - This paper examines patterns of Hispanic concentrated poverty in traditional,
      new, and minor destinations. Using data from 2010 to 2014 from the American
      Community Survey, we find that without controlling for group characteristics,
      Hispanics experience a lower level of concentrated poverty in new destinations
      compared to traditional gateways. Metropolitan level factors explain this
      difference, including ethnic residential segregation, the Hispanic poverty rate,
      and the percentage of Hispanics who are foreign born. Overall, this study sheds
      new light on the Hispanic geographic dispersal in the United States and offers
      support for the argument that the Hispanic settlement into new destinations is
      associated with lower levels of concentrated poverty.

PMID- 29599570
TI  - Landsat-7 ETM+ Radiometric Calibration Status.
AB  - Now in its 17th year of operation, the Enhanced Thematic Mapper + (ETM+), on
      board the Landsat-7 satellite, continues to systematically acquire imagery of the
      Earth to add to the 40+ year archive of Landsat data. Characterization of the
      ETM+ on-orbit radiometric performance has been on-going since its launch in 1999.
      The radiometric calibration of the reflective bands is still monitored using on
      board calibration devices, though the Pseudo-Invariant Calibration Sites (PICS)
      method has proven to be an effect tool as well. The calibration gains were
      updated in April 2013 based primarily on PICS results, which corrected for a
      change of as much as -0.2%/year degradation in the worst case bands. A new
      comparison with the SADE database of PICS results indicates no additional
      degradation in the updated calibration. PICS data are still being tracked though
      the recent trends are not well understood. The thermal band calibration was
      updated last in October 2013 based on a continued calibration effort by NASA/Jet
      Propulsion Lab and Rochester Institute of Technology. The update accounted for a
      0.31 W/m2 sr MUm bias error. The updated lifetime trend is now stable to within
      +/- 0.4K.

PMID- 29599571
TI  - Gender Inequity Associated with Increased Child Physical Abuse and Neglect: a
      Cross-Country Analysis of Population-Based Surveys and Country-Level Statistics.
AB  - Gender inequity is proposed as a societal-level risk factor for child
      maltreatment. However, most cross-national research examining this association is
      limited to developing countries and has used limited measures of gender inequity
      and child homicides as a proxy for child maltreatment. To examine the
      relationship between gender inequity and child maltreatment, we used caregivers'
      reported use of severe physical punishment (proxy for physical abuse) and
      children under 5 left alone or under the care of another child younger than 10
      years of age (supervisory neglect) and three indices of gender inequity (the
      Social and Institutional Gender Index, the Gender Inequality Index, and the
      Gender Gap Index) from 57 countries, over half of which were developing
      countries. We found all three gender inequity indices to be significantly
      associated with physical abuse and two of the three to be significantly
      associated with neglect, after controlling for country-level development. Based
      on these findings, efforts to prevent child abuse and neglect might benefit from
      reducing gender inequity.

PMID- 29599573
TI  - Health Consequences of Poor Oral Health?

PMID- 29599572
TI  - Polymeric dental composites based on remineralizing amorphous calcium phosphate
      fillers.
AB  - For over two decades we have systematically explored structure-composition
      property relationships of amorphous calcium phosphate (ACP)-based polymeric
      dental composites. The appeal of these bioactive materials stems from their
      intrinsic ability to prevent demineralization and/or restore defective tooth
      structures via sustained release of remineralizing calcium and phosphate ions.
      Due to the compositional similarity of the ACP to biological tooth mineral, ACP
      based composites should exhibit excellent biocompatibility. Research described in
      this article has already yielded remineralizing sealants and orthodontic
      adhesives as well as a prototype root canal sealer. Our work has also contributed
      to a better understanding on how polymer matrix structure and filler/matrix
      interactions affect the critical properties of these polymeric composites and
      their overall performance. The addition of antimicrobial compounds to the
      formulation of ACP composites could increase their medical and dental
      regenerative treatment applications, thereby benefiting an even greater number of
      patients.

PMID- 29599574
TI  - Adult Rhabdomyoma of the Tongue in a Child: Report of a Case and a Literature
      Appraisal.
AB  - Rhabdomyoma, by definition is a benign muscle tumour.. Rhabdomyomas constitute 2%
      of all myogenous neoplasms. This tumour is in incongruence with other benign soft
      tissue tumours, in that it is rarer than its malignant counterpart. They are
      broadly categorised as cardiac and extra-cardiac. Three different subtypes exists
      as 1) the adult type, 2) the fetal type and 3) the genital type, the adult type
      being the most common.[1] AR (Adult Rhabdomyoma) generally occurs in the 4th and
      5th decade with a male predilection.[2] There have been very few presentations of
      this lesion in the paediatric age group. Here we present a case of lingual adult
      rhabdomyoma in an 11 year old girl.

PMID- 29599575
TI  - Detection of Hepatitis C Virus RNA in Blood and Saliva of Transfusion-Dependent
      Thalassemia Patients Diagnosed with Hepatitis C.
AB  - Background: The aim of the current study was to detect hepatitis C virus (HCV)
      RNA in blood and saliva of a population of patients with thalassemia who have HCV
      antibody in their serum. Materials and Methods: In this cross-sectional study,
      blood and saliva samples were collected and were analyzed with quantitative
      reverse transcription polymerase chain reaction (RT-PCR) for the detection of HCV
      RNA. In addition, liver-related blood tests were performed, and patients' medical
      history was recorded. Data were analyzed by independent samples t-test and Chi
      square with a significant level of 0.05. Results: Overall, 62 adult patients (29
      males and 33 females) were included. Most (87%) of the patients had major
      thalassemia and genotype 1a was the most common (42%) type. HCV RNA was detected
      in 71 and 16% of blood and saliva samples, respectively. HCV RNA was detected
      more in female patients (31%) (P = 0.003) and in intermediate thalassemia (50%)
      (P < 0.005). The mean age of the patients with positive saliva was almost 10
      years older (P < 0.001), and the mean number of blood transfusion was fewer in
      positive saliva group (P = 0.037). The sensitivity, specificity, and positive and
      negative predictive values of saliva PCR was calculated to be 18%, 88%, 80%, and
      69%, respectively. Conclusion: Saliva contained HCV RNA in 16% of the assessed
      population. The probability of detection of HCV RNA in saliva increased in older
      patients, less number of blood transfusions, females and intermediate
      thalassemia. Saliva RT-PCR demonstrated low sensitivity and high specificity with
      high positive predictive value in the assessed population.

PMID- 29599576
TI  - Evaluation of Bond Strength and Load Deflection Rate of Multi-stranded Fixed
      Retainer Wires: An In-Vitro Study.
AB  - Background: Fixed orthodontic retainers must be well retained on the tooth
      surfaces, allow physiologic movement of teeth and exert minimal forces on the
      teeth to be retained. Previous studies analyzed the bond strength and amount of
      deflection caused due to the debonding force but not the magnitude of force
      needed for unit deformation. Aims: This study aims to evaluate and compare the
      bond strength and load deflection rate (LDR) of three different fixed retainer
      wires. Materials and Methods: The wires were divided into three Groups: A - three
      stranded twisted ligature wire, B - Bond-A-Braid (Reliance Orthodontics), and C -
      three-stranded twisted lingual retainer wire (3M Unitek). Twenty models were
      prepared for each group with a passive 15 mm long lingual retainer wire bonded to
      two lower incisors. An occlusogingival force was applied to the wire until it
      debonded. For LDR, three-point bending test was done at 0.5 mm deflection. These
      forces were measured using a Universal Instron Testing Machine. Statistical
      Analysis: Mean bond strength/LDR and pairwise comparisons were analyzed with one
      way ANOVA and Tukey's honest significant difference post hoc test, respectively.
      Results: Group C exhibited the highest mean bond strength and LDR of 101.17N and
      1.84N, respectively. The intergroup comparisons were all statistically
      significant. Conclusion: Compared to the other two wire types, Group C might be
      better retained on the teeth due to its higher bond strength. With its relatively
      higher LDR value, it may resist deformation from occlusal forces, thereby
      reducing inadvertent tooth movement and yet remain flexible enough to allow
      physiologic tooth movements.

PMID- 29599577
TI  - Microphotographic Assessment of Enamel Surface using Self-Etching Primer and
      Conventional Phosphoric Acid: An In vitro Study.
AB  - Introduction: Conventional acid-etching method irreversibly removes several
      microns of enamel surface and also involves many steps. Hence, a simplified
      technique that minimizes enamel loss, improves adhesion procedures, prevents
      saliva contamination, and saves chair time, thereby producing clinically useful
      bond strength, would be valuable. Aim: To assess and compare the bonding
      mechanism of a self-etching primer (SEP) to that of phosphoric acid on enamel of
      the human permanent teeth by a scanning electron microscope (SEM). Materials and
      Methods: Thirty freshly extracted premolars were randomly divided into two groups
      of fifteen teeth each - the control group I (phosphoric acid) and experimental
      group II (self-etching primer). Brackets were bonded using Transbond XT adhesive
      on the buccal surfaces of the teeth after etching and priming according to their
      respective protocols. The teeth were then sectioned and the samples were
      subjected to a protocol of demineralization cycles. After complete dissolution of
      dental tissues, the specimens were gold sputter coated and evaluated under SEM.
      Results: A characteristically uniform etch pattern was seen in the resin samples
      of the phosphoric acid/Transbond XT primer group, which revealed increased
      roughness and resin tags penetrating the demineralized enamel surface, whereas
      with Transbond Plus SEP, a regular resin tag distribution was observed which
      showed less magnitude when compared with the control group. Conclusion: From the
      study, it was concluded that Transbond Plus SEP produced an etch pattern which
      was more conservative than conventional phosphoric acid system.

PMID- 29599578
TI  - Surface Detail Reproduction and Dimensional Stability of Contemporary
      Irreversible Hydrocolloid Alternatives after Immediate and Delayed Pouring.
AB  - Purpose: To overcome the poor dimensional stability of irreversible
      hydrocolloids, alternative materials were introduced. The dimensional changes of
      these alternatives after delayed pouring are not well studied and documented in
      the literature. The purpose of the study is to evaluate and compare the surface
      detail reproduction and dimensional stability of two irreversible hydrocolloid
      alternatives with an extended-pour irreversible hydrocolloid at different time
      intervals. Materials and Methods: All testing were performed according to the
      ANSI/ADA specification number 18 for surface detail reproduction and
      specification number 19 for dimensional change. The test materials used in this
      study were newer irreversible hydrocolloid alternatives such as AlgiNot FS, Algin
      X Ultra FS, and Kromopan 100 which is an extended pour irreversible hydrocolloid
      as control. The surface detail reproduction was evaluated using stereomicroscope.
      The dimensional change after storage period of 1 h, 24 h, and 120 h was assessed
      and compared between the test materials and control. The data were analyzed using
      one-way ANOVA and post hoc Bonferroni test. Results: Statistically significant
      results (P < 0.001) were seen when mean scores of the tested materials were
      compared with respect to reproduction of 22 MUm line from the metal block.
      Kromopan 100 showed statistically significant differences between different time
      intervals (P < 0.001) and exhibited more dimensional change. Algin-X Ultra FS
      proved to be more accurate and dimensionally stable. Conclusions: Newer
      irreversible hydrocolloid alternative impression materials were more accurate in
      surface detail reproduction and exhibited minimal dimensional change after
      storage period of 1 h, 24 h, and 120 h than extended-pour irreversible
      hydrocolloid impression material.

PMID- 29599580
TI  - Prevalence and Severity of Temporomandibular Disorders among the Orthodontic
      Patients Using Fonseca's Questionnaire.
AB  - Objective: The purpose of the study is to determine the prevalence of TMDs among
      the 12-18 years and 19-30 years patient age group requiring orthodontic treatment
      by using the Fonseca's questionnaire. Material and Methods: A total of 390
      patients who visited the orthodontic department for treatment were asked to fill
      Fonseca's questionnaire. The results were analyzed for both the age groups and
      the percentage values were compared between males and females, different types of
      malocclusion and presence of TMDs. Results: In the 12-18 years age group, around
      18.75% of the males and 12.28% of the females were having some degree of TMJ
      dysfunction. In the 19-30 years age group, around 30.32% of the females were
      found to have some severity of TMJ dysfunction as opposed to 19.23% of males. In
      the 12-18 years age group, around 11% of Class I, 16% of Class II and 50% of
      class III patients were having some degree of temporomandibular dysfunction. In
      the 19-30 years age group, the results showed that around 24% of Class I and
      class II patients and 50% of Class III patients presented with some degree of
      TMD. In the 12-18 years age group around 15% and in the 19-30 years age group,
      around 25% of the patients presented with some degree of TMD ranging from mild,
      moderate to severe. Conclusion: The study concludes that significantly more
      number of females presented with TMDs as compared to males in the 19-30 years age
      group. As the age increases the presence of TMDs also increases because of the
      significant presence of TMDs in the 19-30 years age group as compared to 12-18
      years age group.

PMID- 29599579
TI  - Influence of Infected Root Dentin on the Bond Strength of a Self-adhesive Resin
      Cement.
AB  - Aim: The aim of this study was to determine the bond strength (BS) of a self
      adhesive resin cement to the contaminated root dentin. Materials and Methods: The
      crown and apical third of twenty single-rooted teeth were removed. The root
      canals were flared and 1-mm-thick root sections were obtained. The sections were
      rinsed, dried, and sterilized. The control group (n=20) was composed of one
      section of each third, which remained immersed in sterile trypticase soy broth
      (TSB) for 2 months. The other sections comprised the experimental group (n = 40)
      and were immersed in a suspension of Enterococcus faecalis. The culture medium
      was changed at every 4 days for 2 months. The sections were rinsed with distilled
      water, dried, and the root canal space was filled with the self-adhesive resin
      cement RelyXTM U200. After 24 h, the push-out test was performed and the types of
      interface failure were observed on a stereo microscope. Statistical Analysis:
      Data were statistically analyzed by the nonparametric Mann-Whitney test
      (alpha=5%). Results: A significant reduction was observed in the BS of resin
      cement to the contaminated dentin compared to the healthy dentin, for both thirds
      analyzed (P < 0.05). The BS was significantly greater at the cervical third
      compared to the middle third for specimens in the experimental group (P < 0.05).
      Adhesive and mixed failures were observed more frequently in specimens
      contaminated with E. faecalis. Conclusion: Bacterial contamination negatively
      infl uenced the BS of the self-adhesive resin cement to the root dentin, and
      there was a predominance of adhesive and mixed failures.

PMID- 29599581
TI  - Osteonecrosis of the Jaw among Patients Receiving Antiresorptive Medication: A 4
      year Retrospective Study at a Tertiary Cancer Center, Kerala, India.
AB  - Purpose: Osteonecrosis of the jaw (ONJ) is a rare but complicated side effect of
      antiresorptive medications. The aim of the study is to evaluate the dental and
      drug-related factors related to ONJ among patients on these drugs at a tertiary
      cancer center, India. Methodology: A retrospective record review of patients who
      received antiresorptive medication at our center from 2011 to 2014 was done. The
      demographic factors, type, dosage, and duration of the medication and dental
      history were collected, and the data were entered an analyzed using Epidata
      software. Results: A higher incidence of ONJ (8.1%) was noted in our sample (n =
      183). Dental intervention after zoledronic acid (ZA) administration showed a
      statistical significance (P < 0.001). No significance (P value) was noted with
      respect to sex (0.78), age (0.28), median duration (0.9), and median dosage (0.9)
      of ZA. Conclusion: Oro-dental screening and dental monitoring shall reduce the
      incidence of ONJ. Within the limitations of our study, no significant relation
      could be pointed toward the dosage and duration of the drug and development of
      ONJ.

PMID- 29599582
TI  - Clinical Evaluation of Role of Dual Antiplatelet Therapy on Bleeding after Dental
      Extraction.
AB  - Aims and Objectives: Altered platelet function and increased bleeding time (BT)
      can occur with antiplatelet therapy. This study was conducted to evaluate the
      need for stoppage of dual antiplatelet therapy in patients undergoing dental
      extractions. Materials and Methods: One hundred and fifty patients indicated for
      dental extraction were grouped as Group I: Consisted of 75 patients on dual
      antiplatelet therapy and Group II: Consisted of 75 patients who have discontinued
      antiplatelet therapy 1 week before dental extraction. BT of all the participants
      was recorded before extraction procedures. Under local anesthesia, single molar
      tooth indicated for simple extraction was done in both the groups. Suturing along
      with pressure pack was done after extraction. BT after extraction was
      statistically checked between the groups after 1 h and 24 h using Chi-square test
      with P < 0.05. Results: Postoperatively, none of the patients in both the groups
      showed active bleeding 1 h and 24 h. No bleeding was seen in 73 patients in Group
      I and 78 patients in Group II after 24 h. Conclusion: This study concluded that
      there is no significant difference in BT in both the groups. Antiplatelet
      monotherapy or even antiplatelet dual therapy needs no alteration or stopped
      before minor oral surgical procedures. Most of the postoperative bleeding can be
      easily controlled by local hemostatic measures.

PMID- 29599583
TI  - Evaluation of Antibacterial Efficacy of Fungal-Derived Silver Nanoparticles
      against Enterococcus faecalis.
AB  - Background: The main objective of endodontic therapy is complete elimination and
      prevention of bacteria from the root canal system; however, it is difficult due
      to anatomical ramifications of root canal system and growing resistant microbes
      to available disinfectants. Therefore, to overcome this problem, newer
      antimicrobial agents have to be developed. Aims: The aim of the study was to
      evaluate the antibacterial efficacy of fungal-derived biosynthesized silver
      nanoparticles (AgNPs) against Enterococcus faecalis. Materials and Methods:
      Freshly prepared silver nanoparticles using the endophytic fungi Fusarium
      semitectum, characterized by different techniques were used to evaluate the
      antibacterial efficacy against E. faecalis by agar well diffusion method
      measuring the zone of inhibition using different concentrations of nanoparticles
      (AgNPs) (A [20 MUl], B [40 MUl], C [60 MUl], D [80 MUl], and E [100 MUl]), F
      (0.2% chlorhexidine [CHX]), G (2% CHX), H (ampicillin), and I (distilled water)
      were used as control groups. Statistical Analysis Used: One-way ANOVA followed by
      post hoc Tukey multiple comparison test was done. Results: AgNPs (100 ml) showed
      highest zone of inhibition 19.5 mm against E. faecalis. CHX (0.2%) 14.52 mm, CHX
      (2%) 20.02 mm, and ampicillin showed highest mean zone of inhibition 20.5 mm and
      distilled water showed no zone of inhibition. Results indicate no significant
      difference between E (100 MUl), G (2% CHX), and H (ampicillin) (P < 0.0001).
      Conclusions: Biosynthesized AgNPs exhibit efficient antibacterial activity
      against E. faecalis and therefore can be used as root canal irrigant or
      intracanal medicament for root canal disinfection.

PMID- 29599584
TI  - Assessment of Effect of Age, Gender, and Dentoalveolar Changes on Mandibular
      Morphology: A Digital Panoramic Study.
AB  - Introduction: With progressive development in the growth and function of the
      jaws, changes are observed in size as well as shape of the mandible, which vary
      on the basis of age, gender, and dental status. The objective of this study was
      to evaluate and assess the morphological changes of the mandible, with varying
      age, gender, and dental status, using panoramic radiographs. Materials and
      Methods: A retrospective study was conducted using digital panoramic radiographs
      taken by Kodak 8000c digital panoramic and cephalometric system on 150 patients,
      comprising fifty edentulous individuals (above 50 years of age), fifty old
      dentate individuals (above 50 years of age), and fifty young dentate individuals
      (below 25 years of age). All the mandibular measurements (gonial angle, ramus
      length, condylar length (CL), ramus notch depth, and cortical bone thickness)
      were carried out using RadiAnt DICOM VIEWER 2.2.9 (32-bit) software. The
      measurements were then subjected to paired t-test, Tukey's multiple post hoc
      procedures, and multiple linear regression analysis. Results: Descriptive
      statistics for all the parameters on the right and left sides of the mandible in
      both males and females were analyzed. A statistical significance of P < 0.05 was
      observed for all the variables except one variable (CL). Conclusion: In the
      present study, all the variables showed increased measurements in males except
      gonial angle, which was found to be wider in females, indicating that women tend
      to get affected by varying dental statuses than men. Hence, the parameters used
      in this study may act as good indicators for the assessment of the effect of age,
      gender, and dental status on mandibular morphology.

PMID- 29599585
TI  - Simvastatin Effects on Dental Socket Quality: A Comparative Study.
AB  - Background: The shrinkage of the alveolar ridge might be minimized by the ridge
      preservation stages and applied alloplasts, after tooth extraction. According to
      studies on statins, angiogenesis and osteogenesis are observed as a topical
      application of these drugs. Objectives: The aim of this study is to the
      application of simvastatin in terms of bone regeneration of the alveolar ridge
      after tooth extraction. Materials and Methods: This study assessed this issue
      through the split-mouth method which assessed 10 dental sockets filled with
      simvastatin and collagen and 10 others filled just by collagen postextraction.
      The histological process of bone samples was observed under light microscope
      after 2 months at the time of fixture insertion to evaluate live and dead bone,
      trabecular, amorphous, and nonosteoblastic. The statistical analysis was assessed
      using Mann-Whitney U-test and level of significance was considered <0.05.
      Results: Normal bone was detected in both groups. In simvastatin group, the
      percentages of vital bone, amorphous, and trabecular bone were more than the
      other group and the percentages of dead bone and nonosteoblastic were lower,
      although there was no significant difference in the results. Conclusion: Based on
      study results, simvastatin possibly can improve the quality of osteogenesis in
      the jaw bone; however, further studies are necessary to definitively result.

PMID- 29599586
TI  - Evaluation of Surface Quality of Silicone Impression Materials after Disinfection
      with Ozone Water: An In vitro Study.
AB  - Purpose: To compare and evaluate the surface quality of silicone impression
      materials after ozone water disinfection. Materials and Methods: A total of 60
      samples were prepared on a stainless steel die (American Dental Association
      specification no. 19 and International Standard of Organization - 4823). The
      samples were divided into four groups; each group contains 15 samples. Group A as
      control, Group B, C, and D disinfected with 2% glutaraldehyde, 5.25% sodium
      hypochlorite, and ozone water, respectively. The samples were made according to
      the manufacturer's instructions, and the samples were allowed to set in a
      thermostatically controlled water bath at 35 degrees C +/- 1 degrees C and
      retrieved after 10 min. The surface qualities of the samples were measured in
      stereomicroscope with *20 magnification. Results: The data obtained were analyzed
      using Chi-square test, and the "P" value was calculated. The results showed that
      there were no differences in the surface quality among the Groups A, C, and D for
      addition silicone putty and light body and medium body impression materials than
      the Group B. Conclusion: This study concluded that ozone water disinfection
      showed least changes when compared to 5.25%sodium hypochloride and 2%
      glutaraldehyde disinfection for addition silicone putty , light body and medium
      body impression materials.

PMID- 29599587
TI  - To Evaluate the Efficacy of Topical Propolis in the Management of Symptomatic
      Oral Lichen Planus: A Randomized Controlled Trial.
AB  - Introduction: Lichen planus (LP) is a chronic inflammatory, autoimmune,
      mucocutaneous disease of unknown etiology. The first line of treatment for oral
      LP (OLP) has been corticosteroids, but because of their adverse effects,
      alternative therapeutic approaches are being carried out, of which the recent
      natural alternative is propolis. Aim: This study aims to evaluate the efficacy of
      topical propolis in the management of OLP. Materials and Methods: The research
      group consisted of 27 patients diagnosed with symptomatic OLP, among which 15
      patients were in the control group and the rest 12 were in the study group. The
      patients in the control group received triamcinolone acetonide 0.1% (topical
      application) while the patients in the study group received propolis gel. Both
      the groups were evaluated for pain and erythema at baseline (1st visit), first
      follow-up (7th day), and second follow-up (14th day) using numerical rating scale
      and modified oral mucositis index. Results: The patients in both the study and
      control groups showed a statistically significant reduction (P = 0.000 for the
      study group and P = 0.000 for the control group) in pain and erythema scores from
      baseline to second follow-up visit. However, on comparison of the reduction in
      pain and erythema scores between the two groups, the difference was found to be
      statistically insignificant (P = 0.255). Statistical Analysis Used: Chi-square
      and Cramer's V test were used. Conclusion: The topical propolis was found to be
      of comparative effectiveness with respect to triamcinolone acetonide 0.1% in the
      management of OLP.

PMID- 29599588
TI  - Antimicrobial Efficacy of Octenidine Hydrochloride and Calcium Hydroxide with and
      Without a Carrier: A Broth Dilution Analysis.
AB  - Background: An efficient antimicrobial agent action is required for a
      predetermined time period for absolute elimination of root canal microbes. Till
      date, there is limited or no data on the antimicrobial effect of octenidine as an
      intracanal medicament with chitosan (CTS) as a carrier against Candida albicans
      and Enterococcus faecalis. Aim: The aim of this microbiological study was to
      compare the antimicrobial efficacy of octenidine hydrochloride (OHC) and calcium
      hydroxide (Ca[OH]2) as intracanal medicaments, both independently and along with
      CTS as a carrier molecule against the common resistant endodontic pathogens.
      Materials and Methods: A total of 160 single-rooted anterior teeth were selected,
      root canal preparation was done, and teeth were divided into two groups and
      contaminated with C. albicans and E. faecalis, which were further divided into
      four test groups each according to intracanal medicaments used. CTS was used as a
      vehicle for OHC and Ca(OH)2 and antimicrobial assessment was performed on day 2
      and day 7 following broth dilution method. Dentine samples were collected after
      each time interval, and the number of colony-forming units was determined.
      Results: All four medicaments used in this study showed antifungal and
      antibacterial activity that diminished from day 2 to day 7. Group I (OHC alone)
      and Group IV (Ca[OH]2 alone) showed significant antimicrobial activity against C.
      albicans and E. faecalis, respectively, than the other groups. Conclusion: A
      combination of OHC + CTS and Ca(OH)2+ CTS produced inferior results than that of
      the medicaments used alone.

PMID- 29599589
TI  - Direct Linear Measurement of Root Dentin Thickness and Dentin Volume Changes with
      Post Space Preparation: A Cone-Beam Computed Tomography Study.
AB  - Aim: The purpose of the present study was direct linear measurement of dentin
      thickness and dentin volume changes for post space preparation with cone-beam
      computed tomography (CBCT). Materials and Methods: Ten maxillary central incisors
      were scanned, before and after root canal and post space preparation, with
      Orthophos XG three-dimensional hybrid unit. Thirteen axial section scans of each
      tooth from orifice to apex and dentin thickness for buccal, lingual, mesial, and
      distal were measured using proprietary measuring tool and thereafter subjected to
      statistical analysis. Furthermore, dentin volume was evaluated using ITK-SNAP
      software. Results: There was statistically significant difference between the
      dentin thickness in pre- and postinstrumentation (paired t-test) and also between
      different groups (one-way ANOVA). In the shortest post length of 4.5mm the post
      space preparation resulted in 2.17% loss of hard tissue volume, where as 11mm
      longest post length post space preparation resulted in >40% loss of hard tissue
      volume. Conclusion: CBCT axial section scan for direct measurements of root
      dentin thickness can be guideline before and after post space preparation for
      selection of drill length and diameter.

PMID- 29599590
TI  - Correlation between Dentofacial Esthetics and Mental Temperament: A Clinical
      Photographic Analysis Using Visagism.
AB  - Background: "Visagism," a proposed novel concept, makes it possible for the
      patients to express the desirable emotions and personality traits, through their
      smile. According to this concept, clinicians can design a smile that blends with
      the patient's physical appearance, personality, and desires. Aim: To establish a
      relation, if any, between the smile pattern (dentofacial esthetics determined by
      three parameters, i.e., tooth form, long axes of maxillary anterior teeth, and
      connection line between embrasure) and the personality traits (four mental
      temperaments) through the concept of visagism. Settings and Design: A total of
      190 participants aged between 20 and 38 years from a dental college were selected
      for the study. Materials and Methods: The temperaments of the participants were
      identified using a self-reporting questionnaire. The photographs of frontal view
      of teeth in centric occlusion of the participants were captured, and their tooth
      forms, long axes, and embrasure lines were drawn using photograph editing
      software. The type of temperament obtained from the questionnaire for each
      participant was compared with that obtained from photographic evaluation.
      Statistical Analysis Used: The obtained data were statistically analyzed by
      applying Kappa statistics for kappa measure of agreement. Results: There was no
      agreement between temperaments derived through questionnaire and those
      temperaments obtained from the photographic analysis. Conclusion: Although the
      concept of combining the principles of smile design and mental temperaments
      through visagism is an appreciable idea, it lacks a practical approach to create
      a personalized smile for each patient by including mental temperaments at present
      stage.

PMID- 29599591
TI  - Comparison of Tentative Radiographic Working Length with and without grid Versus
      Electronic Apex Locator.
AB  - : The apical termination of obturation is the most important factor influencing
      the success of root canal treatment (RCT). Working length (WL) is the key element
      in achieving this. Aim: The aim of this study is to compare and evaluate the
      preoperative estimated WL with conventional radiograph and with grid radiograph,
      with reference to electronic apex locator (EAL) in single-rooted teeth. Settings
      and Design: Thirty permanent anterior teeth with complete root formation
      indicated for RCT were included in this study. Materials and Methods:
      Conventional radiograph (Group 1) and conventional radiograph with external grid
      (Group 2) were made before access opening. WL with EAL (Group 3) was determined
      after access opening. Statistical Analysis: The statistical package for the
      social sciences (SPSS) version 16.0 (SPSS Inc., Chicago, IL, USA) was used to
      compare the WLs of three groups, and the statistical significance was considered
      to be P <= 0.05. ANOVA, post hoc test were made to measure the intergroup
      comparison, and Pearson correlation values were obtained. Results and Conclusion:
      The results of the study showed a higher correlation between grid WL and apex
      locator WL than conventional WL and apex locator WL. Preoperative metrics with
      radiographic grid along with the apex locator is a better measuring tool compared
      to the conventional radiographic WL in a single-rooted tooth.

PMID- 29599592
TI  - Comparison of Tumor Necrosis Factor-alpha Concentrations in Gingival Crevicular
      Fluid between Self-Ligating and Preadjusted Edgewise Appliances in the Early
      Leveling Stage of Orthodontic Treatment.
AB  - Introduction: Tumor necrosis factor-alpha (TNF-alpha) is an important
      proinflammatory cytokine that regulates the early phase of inflammation reaction
      during orthodontic tooth movement. The aim of the present study was to compare
      TNF-alpha concentrations in the gingival crevicular fluid (GCF) between
      preadjusted edgewise appliance (PEA) and self-ligating (SL) systems during the
      early leveling stage of orthodontic treatment. Materials and Methods: Eighteen
      patients (aged 15-35 years) who participated in this study were divided into two
      experimental groups (PEA and SL) and control group (without orthodontic
      treatment). The GCF was taken at five sites in the maxilla anterior teeth from
      each participant just before bracket bonding and at 1, 24, and 168 h after the
      initiation of tooth movement. Cytokine levels were determined through ELISA.
      Results: The concentration of TNF-alpha was significantly higher in the
      experimental groups than in the control group at 24 h after force application.
      TNF-alpha levels were significantly decreased at 168 h after force application in
      the PEA group. Meanwhile, in the SL group, the level of TNF-alpha at 168 h was
      still increased, although there was no statistically significant difference.
      Conclusion: TNF-alpha concentration was increased at 1 h and 24 h after
      orthodontic force application in both the PEA and SL groups. In the PEA group,
      TNF-alpha concentration was significantly decreased at 168 h, meanwhile in the SL
      group, this value remained increased at this time point. The differences in TNF
      alpha concentration between the PEA and SL groups may be caused by their
      different types of brackets, wires, and ligation methods.

PMID- 29599593
TI  - The Top 10 Ethical Challenges in Dental Practice in Indian Scenario: Dentist
      Perspective.
AB  - Aim: This exploratory qualitative research is an attempt to assess the health
      care ethical challenges in dental practice in an Indian scenario. Methodology:
      Qualitative indepth interview was conducted on 20 dental professionals to assess
      the ethical challenges prevailing in dental practice in Indian scenario. After
      obtaining the responses the verbatims were categorized into categories and
      finally 36 themes emerged. Later from two group of 6 panellists each after
      conducting focus group discussion the themes of ethical issues occurring in
      dental practice were ranked based on order of significance impact on the
      practice, patient and society using Delphi method. Result: The top ten ethical
      challenges listed by the panellists are inadequate sterilization and waste
      management in dental clinics, poor knowledge and attitude towards ethics among
      our dental practitioners, in competence among dental professional, increase in
      cost of oral health service, poor informed consent process, requirement of
      consensus about the treatment procedures among dentists, Conflict in Advertising,
      clustering of dental clinics in urban areas, disagreement with treatment
      modalities among dentist and patient, poor medical record maintenance among our
      dental practitioners. Conclusion: The study attempts to bring the prevailing
      ethical challenges in oral health care practice in Indian scenario.

PMID- 29599594
TI  - Evaluation of Low-Level Laser Therapy on Orthodontic Tooth Movement: A Randomized
      Control Study.
AB  - Background: Fixed orthodontic treatment is time-consuming procedure. Pain is
      usually associated with orthodontic treatment. The aim of the present study was
      to evaluate the role of low-level laser therapy (LLLT) on orthodontic tooth
      movement (OTM) duration and pain perception. Materials and Methods: This
      randomized double-blind splint-mouth controlled clinical study includes 20 (8
      males and 12 females) orthodontic patients requiring bilateral canine retraction.
      Time taken for canine retraction with LLLT (Group A) over control (Group B)
      quadrant on the same patient was assessed along with pain experience using facial
      pain scale. The data were tabulated and statistically evaluated using SPSS 20 for
      windows (Microsoft, Chicago, IL, USA) and t-test with P < 0.05. The difference in
      pain was evaluated with Wilcoxon signed-rank test. Results: There was no
      difference in values for age and sex of patient for tooth movement and pain (P >
      0.05). There was statistically significant decrease in rate of canine retraction
      in Group A compared to Group B. There was statistically significant difference
      for maxillary and mandibular arches in Group A whereas it was not significant in
      Group B. Pain experience was statistically significant till 2nd day, and after
      3rd day, it was not significant between the groups. Conclusion: LLLT can reduce
      the fixed OTM timing and pain experience.

PMID- 29599595
TI  - Non-Hodgkin's Lymphoma of the mandible in HIV patient - A Rare Case Report.
AB  - Non-Hodgkin's lymphoma (NHL) is a lymphatic system tumor originating from either
      B or T lymphocytes and shows a high malignant potential. In HIV-seropositive
      patients, NHL of head and neck is mainly found in Waldeyer's ring, oral mucosa,
      salivary glands, paranasal sinuses, and laryngeal tissue. Primary NHL rarely
      affects the bone. When the lesion affects the bones of the jaws, it is rare in
      the mandible when compared to the maxilla. In the reported cases, only 0.6% are
      found in the mandible. NHL of the mandible can be difficult to diagnose, and so
      the prime aim of the present case report is to establish appropriate diagnosis of
      one of such kinds. Clinically, they may imitate a dental infection with symptoms
      of pain and discomfort. A delay in diagnosis may lead to a poor prognosis.
      Herewith, we present a case of NHL on the lower-right mandible in a 40-year-old
      male. A correlation of clinical findings, radiological examination, and
      histopathological examination enabled us in early diagnosis and differentiating
      it from other similar conditions, thus aiding in initiation of prompt treatment.

PMID- 29599596
TI  - Diode Laser and Periodontal Regeneration-Assisted Management of Implant
      Complications in Anterior Maxilla.
AB  - Dental implant is being considered successful if the patient is pleased with both
      of its functional and esthetic outcome. As implant complications (such as peri
      implantitis, inappropriate implant position, wrong angulation, and implant
      location too close to anatomical structures) have been frequently encountered in
      dental practice, therefore, thorough knowledge to manage such complications is
      the key prerequisite to prevent the failure of implant. The present case report
      discussed the etiology, diagnosis of early peri-implantitis, and periodontal
      abscess with their successful management through periodontal regeneration and
      diode laser-assisted therapy.

PMID- 29599597
TI  - Prosthetic Rehabilitation of Hemimandibulectomy Defect with Removable Partial
      Denture Prosthesis Using an Attachment-Retained Guiding Flange.
AB  - The restoration of normal function and esthetics is often challenging in the
      prosthetic rehabilitation of patients with hemimandibulectomy defects due to
      unstable occlusion and mandibular deviation. The extensive period of time for
      completion of healing of the reconstructed mandible through reconstructive
      plastic surgery and/or implant-assisted prosthesis may compromise the masticatory
      function by causing delay in the fabrication of definitive prosthesis. This case
      report describes a novel technique for the construction of customized attachment
      retained mandibular guiding flange prosthesis for immediate rectification of the
      frontal plane rotation occurring after hemimandibulectomy.

PMID- 29599598
TI  - Gingival Veneer Used as Prosthetic Solution for Esthetic-Compromised
      Malpositioned Dental Implant.
AB  - Implant therapy has become a common practice and esthetic demands have
      tremendously increased, especially in the replacement of anterior teeth in
      patients with a high lip line. This report presents a gingival veneer as a viable
      treatment modality to mask peri-implant marginal gingival defects. An impression
      of the upper arch was made and the gingival veneer was waxed, and clinical
      confirmation was obtained, followed by laboratory processing, finishing, and
      polishing. After installing, it adapted to the proximal niches and exhibited good
      stability. A gingival veneer can be a feasible alternative with excellent
      esthetic results, when indicated and correctly executed to mask possible defects
      in the peri-implant marginal gingiva associated with a malpositioned single
      dental implant.

PMID- 29599599
TI  - Diagnosis, Treatment Planning, and Full-mouth Rehabilitation in a Case of
      Amelogenesis Imperfecta.
AB  - Amelogenesis imperfecta is a genetic condition affecting the teeth resulting in
      aberrations of the structure and clinical appearance of enamel. The treatment of
      amelogenesis imperfecta involves a multidisciplinary treatment approach requiring
      a comprehensive examination, diagnosis, and effective treatment planning strategy
      along with satisfaction of patient-related factors. The clinical case described
      here involves judicious involvement of different disciplines to formulate a
      treatment plan best suitable to confirm with the patient's needs and
      expectations, at the same time maintaining the integrity and harmony of
      associated hard and soft tissues.

PMID- 29599600
TI  - An Enigmatic Clinical Presentation of Plasma Cell Granuloma of the Oral Cavity.
AB  - Plasma cell granuloma is a rare benign lesion characterized by the infiltration
      of plasma cells; primarily occurring in the lungs. It is also seen to occur in
      the brain, kidney stomach, heart, and so on but its intraoral occurrence is a
      rarity. This case report represents one of the uncommon locations in the oral
      cavity affected by plasma cell granuloma, its clinical and histological features,
      and establishes the differential diagnosis with other malignant or benign disease
      entities and planning the treatment accordingly. This report discusses the
      diagnostic enigma and the associated terminology of plasma cell granulomas and
      reinforces the need for performing biopsy and a histopathological or immune
      histochemical study, irrespective of the clinical features and clinical diagnosis
      of the lesion. In this case a 52-year-old female, presented with gingival
      enlargement in the mandibular anterior region, treated by excisional biopsy.
      Histological evaluation revealed plasma cell infiltrates in the connective
      tissue. The immune-histochemistry revealed kappa and lambda light chains with a
      polyclonal staining pattern, which confirmed the diagnosis of plasma cell
      granuloma.

PMID- 29599601
TI  - Endodontic Management of Radix Entomolaris in Second Molar.
AB  - The presence of radix entomolaris (RE) in a mandibular first molar is a common
      occurrence, which accounts for 0.2%-32% of the population, but the presence of RE
      in a mandibular second molar is a rare occurrence in our ethnic group. This
      presence of additional root can lead to difficulties during endodontic treatment.
      A thorough knowledge of anatomy is necessary for the success of endodontic
      treatment. This article presents a review on clinical approach and a case series
      on the detection and management of RE on mandibular second molar. RE was
      identified using Same lingual opposite buccal (SLOB) technique with preoperative
      radiograph, modifying the access cavity preparation, locating the canals followed
      by cleaning, and shaping of canals with nickel-titanium instruments. Obturation
      was done with respective master cones and AH + resin sealer.

PMID- 29599602
TI  - PGI Bracket Positioner: A Novel Combination of Reverse Bracket Tweezer and
      Positioning Gauze.
AB  - The accurate bracket positioning is essential for the expression of the bracket
      system that affects the treatment outcome considerably and is also essential for
      good functional occlusion as well as facial esthetics. The proper alignment
      cannot be achieved without proper bracket positioning. Thus, the brackets
      positioning devices are an integral part of orthodontic armamentarium. Here, we
      present a new innovation that provides a unique combination of reverse bracket
      tweezer and positioner and hence is very helpful in precise vertical positioning
      of brackets with increased efficiency.

PMID- 29599603
TI  - Sleeve Push Technique: A Novel Method of Space Gaining.
AB  - Space gaining is frequently required in orthodontics. Multiple loops were
      initially used for space gaining and alignment. The most common used mechanics
      for space gaining is the use of nickel-titanium open coil springs. The
      disadvantage of nickel-titanium coil spring is that they cannot be used until the
      arches are well aligned to receive the stiffer stainless steel wires. Therefore,
      a new method of gaining space during initial alignment and leveling has been
      developed and named as sleeve push technique (SPT). The nickel-titanium wires,
      i.e. 0.012 inches and 0.014 inches along with archwire sleeve (protective tubing)
      can be used in a modified way to gain space along with alignment. This method
      helps in gaining space right from day 1 of treatment. The archwire sleeve and
      nickel-titanium wire in this new SPT act as a mutually synergistic combination
      and provide the orthodontist with a completely new technique for space opening.

PMID- 29599605
TI  - Cell culture-adaptive mutations in hepatitis C virus promote viral production by
      enhancing viral replication and release.
AB  - AIM: To explore hepatitis C virus (HCV) adaptive mutations or combinations
      thereof responsible for enhanced viral production and investigate the underlying
      mechanisms. METHODS: A series of plasmids with adaptive mutations were
      constructed. After the plasmids were transfected into Huh7.5 cells, we determined
      the infectious HCV particle titers by NS5A immunofluorescence assays, and
      detected HCV RNA replication by real-time PCR and protein expression by Western
      blot. Then we carried out immunoblotting of supernatants and cell lysates with
      anti-NS3 to analyze the virus release level. In addition, co-localization of
      lipid droplets (LDs) with NS5A was measured using confocal laser scanning
      microscopy. The ratio between the p56 and p58 phosphoforms of NS5A was analyzed
      further. RESULTS: The plasmids named JFH1-mE2, JFH1-mp7, JFH1-mNS4B, JFH1-mNS5A,
      JFH1-mE2/NS5A, JFH1-mp7/NS5A, JFH1-mNS4B/NS5A, JFH1-mE2/p7/NS5A, and mJFH1 were
      constructed successfully. This study generated infectious HCV particles with a
      robust titer of 1.61 * 106 focus-forming units (FFUs)/mL. All of the six adaptive
      mutations increased the HCV particle production at varying levels. The NS5A
      (C2274R, I2340T, and V2440L) and p7 (H781Y) were critical adaptive mutations. The
      effect of NS5A (C2274R, I2340T, and V2440L), p7 (H781Y), and NS4B (N1931S) on
      infectious HCV titers was investigated by measuring the HCV RNA replication,
      protein expression, and virion release. However, the six adaptive mutations were
      not required for the LD localization of NS5A proteins or the phosphorylation of
      NS5A. CONCLUSION: In this study, we generated infectious HCV particles with a
      robust titer of 1.61 * 106 FFUs/mL, and found that the viral replication and
      release levels could be enhanced by some of the adaptive mutations.

PMID- 29599604
TI  - Review article: Update on current and emergent data on hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage
      liver disease, characterized by impaired arterial oxygenation induced by
      intrapulmonary vascular dilatation. Its prevalence ranges from 4% to 47% in
      patients with cirrhosis due to the different diagnostic criteria applied among
      different studies. Nitric oxide overproduction and angiogenesis seem to be the
      hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary
      shunting and ventilation-perfusion mismatch. A classification of HPS according to
      the severity of hypoxemia has been suggested. Contrast-enhanced echocardiography
      represents the gold standard method for the detection of intrapulmonary vascular
      dilatations which is required, in combination with an elevated alveolar arterial
      gradient to set the diagnosis. The only effective treatment which can modify the
      syndrome's natural history is liver transplantation. Although it is usually
      asymptomatic, HPS imparts a high risk of pretransplantation mortality,
      independently of the severity of liver disease, while there is variable data
      concerning survival rates after liver transplantation. The potential of
      myocardial involvement in the setting of HPS has also gained increasing interest
      in recent research. The aim of this review is to critically approach the existing
      literature of HPS and emphasize unclear points that remain to be unraveled by
      future research.

PMID- 29599606
TI  - Serum interleukin-34 level can be an indicator of liver fibrosis in patients with
      chronic hepatitis B virus infection.
AB  - AIM: To investigate whether serum interleukin (IL)-34 levels are correlated with
      hepatic inflammation and fibrosis in patients with chronic hepatitis B virus
      (HBV) infection. METHODS: In this study, serum IL-34 levels were assessed by
      enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with
      chronic HBV infection undergoing biopsy. The frequently used serological markers
      of liver fibrosis were based on laboratory indexes measured at the Clinical
      Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver
      stiffness was detected by transient elastography with FibroTouch. The
      relationships of non-invasive makers of liver fibrosis and IL-34 levels with
      inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other
      liver fibrosis makers were evaluated using areas under the receiver operating
      characteristic curves, sensitivity and specificity. RESULTS: Serum IL-34 levels
      were associated with inflammatory activity in the liver, and IL-34 levels
      differed among phases of chronic HBV infection (P = 0.001). By comparing serum IL
      34 levels among patients with various stages of liver fibrosis determined by
      liver biopsy, we found that IL-34 levels >= 15.83 pg/mL had a high sensitivity of
      86.6% and a specificity of 78.7% for identifying severe fibrosis (S3-S4).
      Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the
      serum makers of liver fibrosis, in identifying severe liver fibrosis and early
      cirrhosis in patients with HBV-related liver fibrosis in China. CONCLUSION: Our
      results indicate that IL-34, a cytokine involved in the induction of activation
      of profibrogenic macrophages, can be an indicator of liver inflammation and
      fibrosis in patients with chronic HBV infection.

PMID- 29599607
TI  - Model combining pre-transplant tumor biomarkers and tumor size shows more utility
      in predicting hepatocellular carcinoma recurrence and survival than the BALAD
      models.
AB  - AIM: To assess the performance of BALAD, BALAD-2 and their component biomarkers
      in predicting outcome of hepatocellular carcinoma (HCC) patients after liver
      transplant. METHODS: BALAD score and BALAD-2 class are derived from bilirubin,
      albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP
      L3), and des-gamma-carboxyprothrombin (DCP). Pre-transplant AFP, AFP-L3 and DCP
      were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard
      ratios (HR) for recurrence and death were calculated. Univariate and multivariate
      regression analyses were conducted. C-statistics were used to compare biomarker
      based to predictive models. RESULTS: During a median follow-up of 12.2 years, 38
      patients recurred and 87 died. The HRs for recurrence in patients with elevated
      AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42 (1.18-5.00), 1.86
      (0.98-3.52), and 2.83 (1.42-5.61), respectively. For BALAD, the HRs for
      recurrence and death per unit increased score were 1.48 (1.15-1.91) and 1.59
      (1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased
      class were 1.45 (1.06-1.98) and 1.38 (1.09-1.76). For recurrence prediction, the
      combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64,
      0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively.
      Similarly, for death prediction, the combination of three biomarkers had the
      highest c-statistic of 0.66 vs 0.65, 0.61, 0.52, and 0.50 for BALAD, BALAD-2,
      Milan, and UCSF. A new model combining biomarkers with tumor size at the time of
      transplant (S-LAD) demonstrated the highest predictive capability with c
      statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION: BALAD and BALAD
      2 are valid in transplant HCC patients, but less predictive than the three
      biomarkers in combination or the three biomarkers in combination with maximal
      tumor diameter (S-LAD).

PMID- 29599608
TI  - Intraoperative frozen section diagnosis of bile duct margin for extrahepatic
      cholangiocarcinoma.
AB  - AIM: To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct
      margins during surgery for extrahepatic cholangiocarcinoma (CCA). METHODS: We
      retrospectively analyzed 74 consecutive patients who underwent surgery for
      extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was
      performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile
      duct margins, respectively). The diagnosis was classified into three categories:
      negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite
      for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer,
      and total layer was compared with corresponding permanent section diagnosis (PSD)
      postoperatively. Then, association between FSD and local recurrence was analyzed
      with special reference to borderline. RESULTS: Analysis of 100 duct margins
      revealed that concordance rate between FSD and PSD was 68.0% in the total layer,
      69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent
      of remaining biliary epithelium was comparable between FSD and PSD, and more than
      half of the margins lost > 50% of the entire epithelium, suggesting low quality
      of the samples. In FSD, the rate of negative margins decreased and that of
      borderline and positive margins increased according to the extent of the
      remaining epithelium. Diagnostic discordance between FSD and PSD was observed in
      31 epithelial layers and two subepithelial layers. Alteration from borderline to
      negative was the most frequent (20 of the 31 epithelial layers). Patients with
      positive margin in the total and epithelial layers by FSD demonstrated a
      significantly worse local recurrence-free survival (RFS) compared with patients
      with borderline and negative margins, which revealed comparable local RFS.
      Patients with borderline and negative margins in the epithelial layer by PSD also
      revealed comparable local RFS. These results suggested that epithelial borderline
      might be regarded substantially as negative. When classifying the status of the
      epithelial layer either as negative or positive, concordance rates between FSD
      and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and
      98.0%, respectively. CONCLUSION: During intraoperative assessment of bile duct
      margin, borderline in the epithelial layer can be substantially regarded as
      negative, under which condition FSD is comparable to PSD.

PMID- 29599609
TI  - Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic
      gastritis.
AB  - AIM: To explore the correlation between serum vitamin B12 level and peripheral
      neuropathy in patients with chronic atrophic gastritis (CAG). METHODS: A total of
      593 patients diagnosed with chronic gastritis by gastroscopy and pathological
      examination from September 2013 to September 2016 were selected for this study.
      The age of these patients ranged within 18- to 75-years-old. Blood pressure,
      height and weight were measured in each patient, and the body mass index value
      was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum
      creatinine tests were performed, and peripheral nerve conduction velocity and
      Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis
      was determined by gastroscopy. The above factors were used as independent
      variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12
      deficiency risk factors, and to analyze the relationship between vitamin B12
      levels and peripheral nerve conduction velocity. In addition, in the treatment of
      CAG on the basis of vitamin B12, patients with peripheral neuropathy were
      observed. RESULTS: Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were
      risk factors for the occurrence of peripheral nerve degeneration. Furthermore,
      CAG and H. pylori infection were risk factors for chronic gastritis associated
      with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated
      with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After
      vitamin B12 supplementation, patients with peripheral neuropathy improved.
      CONCLUSION: Serum vitamin B12 levels in patients with chronic gastritis
      significantly decreased, and the occurrence of peripheral neuropathy had a
      certain correlation. CAG and H. pylori infection are risk factors for vitamin B12
      deficiency and peripheral neuropathy. When treating CAG, vitamin B12
      supplementation can significantly reduce peripheral nervous system lesions.
      Therefore, the occurrence of peripheral neuropathy associated with vitamin B12
      deficiency may be considered in patients with CAG. Furthermore, the timely
      supplementation of vitamin B12 during the clinical treatment of CAG can reduce or
      prevent peripheral nervous system lesions.

PMID- 29599610
TI  - Successful combination of direct antiviral agents in liver-transplanted patients
      with recurrent hepatitis C virus.
AB  - AIM: To analyze the safety and efficiency of direct-acting antiviral (DAA)
      regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection.
      METHODS: Between January 2014 and December 2016, 39 patients with HCV reinfection
      after liver transplantation were treated at our tertiary referral center with
      sofosbuvir (SOF)-based regimens, including various combinations with interferon
      (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen
      patients were treated with SOF + IFN +/- RBV. Ten patients were treated with SOF
      + DAC +/- RBV. Fiveteen patients were treated with fixed-dose combination of SOF
      + LDV +/- RBV. One patient was treated with SOF + SIM + RBV. Three patients with
      relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk
      in all cases. The decision about the HCV treatment was made by specialists at our
      transplant center, according to current available or recommended medications.
      RESULTS: The majority of patients were IFN-experienced (29/39, 74.4%) and had a
      history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation.
      Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of
      patients treated with SOF + IFN +/- RBV. All patients with relapse were treated
      with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC +
      RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment
      with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were
      significantly higher, as compared to all other therapy regimens (P = 0.007).
      Liver function was stable or even improved in the majority of patients during
      treatment. All antiviral therapies were safe and well-tolerated, without need of
      discontinuation of treatment or dose adjustment of immunosuppression. No serious
      adverse events or any harm to the liver graft became overt. No patient
      experienced acute cellular rejection during the study period. CONCLUSION: Our
      cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk
      course of treatment, especially with combination of NS5A and NS5B inhibitors.

PMID- 29599612
TI  - Fourier phase retrieval with a single mask by Douglas-Rachford algorithms.
AB  - The Fourier-domain Douglas-Rachford (FDR) algorithm is analyzed for phase
      retrieval with a single random mask. Since the uniqueness of phase retrieval
      solution requires more than a single oversampled coded diffraction pattern, the
      extra information is imposed in either of the following forms: 1) the sector
      condition on the object; 2) another oversampled diffraction pattern, coded or
      uncoded. For both settings, the uniqueness of projected fixed point is proved and
      for setting 2) the local, geometric convergence is derived with a rate given by a
      spectral gap condition. Numerical experiments demonstrate global, power-law
      convergence of FDR from arbitrary initialization for both settings as well as for
      3 or more coded diffraction patterns without oversampling. In practice, the
      geometric convergence can be recovered from the power-law regime by a simple
      projection trick, resulting in highly accurate reconstruction from generic
      initialization.

PMID- 29599611
TI  - Daclatasvir plus asunaprevir in treatment-naive patients with hepatitis C virus
      genotype 1b infection.
AB  - AIM: To assess daclatasvir plus asunaprevir (DUAL) in treatment-naive patients
      from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype
      1b infection. METHODS: Patients were randomly assigned (3:1) to receive 24 wk of
      treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice
      daily) beginning on day 1 of the treatment period (immediate treatment arm) or
      following 12 wk of matching placebo (placebo-deferred treatment arm). The primary
      endpoint was a comparison of sustained virologic response at posttreatment week
      12 (SVR12) compared with the historical SVR rate for peg-interferon plus
      ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of
      the study were blinded. Safety was assessed in DUAL-treated patients compared
      with placebo patients during the first 12 wk (double-blind phase), and during 24
      wk of DUAL in both arms combined. RESULTS: In total, 207 patients were randomly
      assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most
      patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them,
      13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA
      levels of >= 6 million IU/mL. Among patients in the immediate treatment arm,
      SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was
      significantly higher than the historical comparator rate (70%). SVR12 was largely
      unaffected by cirrhosis (89%), age >= 65 years (92%), male sex (90%), baseline
      HCV RNA >= 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was
      higher among patients without (96%) than among those with (53%) baseline NS5A
      resistance-associated polymorphisms (at L31 or Y93H). During the double-blind
      phase, aminotransferase elevations were more common among placebo recipients than
      among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the
      most common adverse events (>= 10%) were elevated alanine aminotransferase and
      upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities
      were infrequently observed, and all grade 3-4 aminotransferase abnormalities
      (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within
      8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase
      elevations, nausea, and jaundice and the other due to a fatal adverse event
      unrelated to treatment. There were no treatment-related deaths. CONCLUSION: DUAL
      was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%)
      exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

PMID- 29599613
TI  - Dexibuprofen nanocrystals with improved therapeutic performance: fabrication,
      characterization, in silico modeling, and in vivo evaluation.
AB  - Background: The aim of this study was to prepare and evaluate the impact of
      polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced
      therapeutic potential, using a low energy, anti-solvent precipitation method
      coupled with molecular modelling approach. Methods: Dexi nanocrystals were
      prepared using antisolvent precipitation with syringe pump. Crystallinity of the
      processed Dexi particles was confirmed using differential scanning calorimetry
      and powdered X-ray diffraction and transmission electron microscopy. Dissolution
      of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular
      modelling study was coupled with experimental studies to rationalise the
      appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was
      carried out using balb mice. Results: Combinations of hydroxypropyl
      methylcellulose (HPMC)-polyvinyl pyrrolidone (PVP) and HPMC-Eudragit (EUD) were
      shown to be very effective in producing stable Dexi nanocrystals with particle
      sizes of 85.0+/-2.5 nm and 90+/-3.0 nm, and polydispersity of 0.179+/-0.01,
      0.182+/-0.02, respectively. The stability studies conducted for 90 days
      demonstrated that nanocrystals stored at 2 degrees C-8 degrees C and 25 degrees C
      were more stable than those at 40 degrees C. The maximum recovery of Dexi
      nanocrystals was observed from the formulations using the combination of HPMC-PVP
      and HPMC-EUD, which equated to 98% and 94% of the nominal active drug content
      respectively. The saturation solubility of the Dexi nanocrystals was
      substantially increased to 270.0+/-3.5 MUg/mL compared to the raw Dexi in water
      (51.0+/-2.0 MUg/mL) and stabilizer solution (92.0+/-3.0 MUg/mL). Enhanced
      dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the
      unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the
      analgesic effect at much lower doses (5 mg/kg) than that of control standard,
      diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg). Conclusion: HPMC
      PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi
      nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility
      and analgesic effect compared to the raw Dexi and the control standard diclofenac
      sodium.

PMID- 29599614
TI  - Interaction of poly-l-lysine coating and heparan sulfate proteoglycan on magnetic
      nanoparticle uptake by tumor cells.
AB  - Background: Poly-l-lysine (PLL) enhances nanoparticle (NP) uptake, but the
      molecular mechanism remains unresolved. We asked whether PLL may interact with
      negatively charged glycoconjugates on the cell surface and facilitate uptake of
      magnetic NPs (MNPs) by tumor cells. Methods: PLL-coated MNPs (PLL-MNPs) with
      positive and negative zeta-potential were prepared and characterized. Confocal
      and transmission electron microscopy was used to analyze cellular internalization
      of MNPs. A colorimetric iron assay was used to quantitate cell-associated MNPs
      (MNPcell). Results: Coadministration of PLL and dextran-coated MNPs in culture
      enhanced cellular internalization of MNPs, with increased vesicle size and
      numbers/cell. MNPcell was increased by eight- to 12-fold in response to PLL in a
      concentration-dependent manner in human glioma and HeLa cells. However, the
      application of a magnetic field attenuated PLL-induced increase in MNPcell. PLL
      coating increased MNPcell regardless of zeta-potential of PLL-MNPs, whereas
      magnetic force did not enhance MNPcell. In contrast, epigallocatechin gallate and
      magnetic force synergistically enhanced PLL-MNP uptake. In addition, heparin, but
      not sialic acid, greatly reduced the enhancement effects of PLL; however, removal
      of heparan sulfate from heparan sulfate proteoglycans of the cell surface by
      heparinase III significantly reduced MNPcell. Conclusion: Our results suggest
      that PLL-heparan sulfate proteoglycan interaction may be the first step mediating
      PLL-MNP internalization by tumor cells. Given these results, PLL may facilitate
      NP interaction with tumor cells via a molecular mechanism shared by infection
      machinery of certain viruses.

PMID- 29599616
TI  - Nursing Competency: Definition, Structure and Development.
AB  - Nursing competency includes core abilities that are required for fulfilling one's
      role as a nurse. Therefore, it is important to clearly define nursing competency
      to establish a foundation for nursing education curriculum. However, while the
      concepts surrounding nursing competency are important for improving nursing
      quality, they are still not yet completely developed. Thus, challenges remain in
      establishing definitions and structures for nursing competency, competency levels
      necessary for nursing professionals, training methods and so on. In the present
      study, we reviewed the research on definitions and attributes of nursing
      competency in Japan as well as competency structure, its elements and evaluation.
      Furthermore, we investigated training methods to teach nursing competency.

PMID- 29599615
TI  - Biomimetic mineralized strontium-doped hydroxyapatite on porous poly(l-lactic
      acid) scaffolds for bone defect repair.
AB  - Introduction: poly(l-lactic acid) (PLLA) has been approved for clinical use by
      the US Food and Drug Administration (FDA); however, their stronger hydrophobicity
      and relatively fast degradation rate restricted their widespread application. In
      consideration of the composition of bone, the inorganic-organic composite has a
      great application prospect in bone tissue engineering. Many inorganic-organic
      composite scaffolds were prepared by directly mixing the active ingredient, but
      this method is uncontrolled and will lead to lack of homogeneity in the polymer
      matrix. Strontium (Sr) is an admirable addition to improve the bioactivity and
      bone induction of hydroxyapatite (HA). To our knowledge, the application of
      biomimetic mineralized strontium-doped hydroxyapatite on porous poly(l-lactic
      acid) (Sr-HA/PLLA) scaffolds for bone defect repair has never been reported till
      date. Biomimetic mineralized Sr-HA/PLLA porous scaffold was developed in this
      study. The results indicated that the Sr-HA/PLLA porous scaffold could improve
      the surface hydrophobicity, reduce the acidic environment of the degradation, and
      enhance the osteoinductivity; moreover, the ability of protein adsorption and the
      modulus of compression were increased. The results also clearly showed the
      effectiveness of the Sr-HA/PLLA porous scaffold in promoting cell adhesion,
      proliferation, and alkaline phosphatase (ALP) activity. The micro computed
      tomography (micro-CT) results showed that more new bones were formed by Sr
      HA/PLLA porous scaffold treatment. The histological results confirmed the
      osteoinductivity of the Sr-HA/PLLA porous scaffold. The results suggested that
      the Sr-HA/PLLA porous scaffold has a good application prospect in bone tissue
      engineering in the future. Purpose: The purpose of this study was to promote the
      bone repair. Materials and methods: Surgical operation of rabbits was carried out
      in this study. Results: The results showed that formation of a large number of
      new bones by the Sr-HA/PLLA porous scaffold treatment is possible. Conclusion:
      Biomimetic mineralized Sr-HA/PLLA porous scaffold could effectively promote the
      restoration of bone defects in vivo.

PMID- 29599618
TI  - A Survey of Epilepsy-related Knowledge, Attitudes and Practices of Home
      Healthcare Nurses in the San-in Region of Japan.
AB  - Background: Comprehensive care is necessary for people with epilepsy (PWE) to
      lead a fulfilling life at home and in the community. The purpose of this study
      was to determine the epilepsy-related knowledge, attitudes and practices of home
      healthcare nurses (HHNs) in the San-in region of Japan. Methods: A questionnaire
      survey was conducted by mail of 546 HHNs working in Tottori and Shimane
      Prefectures. The questionnaire assessed the epilepsy-related knowledge, attitudes
      and practices of HHNs. For the analysis, simple and cross tabulation of
      questionnaire responses were conducted, and the chi-squared test was used for
      statistical testing. Results: A total of 285 HHNs participated in the study. Of
      the respondents, 43.9% had experience taking care of PWE in a home healthcare
      nursing setting. Regarding the cause of epilepsy, in descending order the
      percentage of correct responses were 86.7% for stroke, 85.3% for head injury, and
      only 13.3% for dementia. Concerning how to respond to an epileptic seizure,
      almost all respondents answered correctly, but 29.8% gave the incorrect answer of
      "place something inside the mouth." Regarding the practices of HHNs in relation
      to caring for PWE, nurses scored 52.0% for collaborating with the attending
      physician, indicating the need for improvement. The score for "provide
      information about social resources" was low at 18.4%. Of the respondents, 95.8%
      answered that epilepsy-related knowledge and technical skills were necessary for
      home healthcare nursing practice, and 87.7% were interested in participating in a
      workshop on epilepsy. Conclusion: The study revealed an inadequate level of
      knowledge of epilepsy with dementia and corresponding epileptic seizures, a low
      awareness of nursing care in collaboration with physicians, and the importance of
      providing information about social resources. There is a need to offer
      information and education on the latest knowledge about epilepsy to HHNs.

PMID- 29599617
TI  - Resolvin E1 Inhibits Osteoclastogenesis and Bone Resorption by Suppressing IL-17
      induced RANKL Expression in Osteoblasts and RANKL-induced Osteoclast
      Differentiation.
AB  - Background: Resolvin E1 (RvE1) derived from the omega-3 polyunsaturated fatty
      acid eicosapentaenoic acid is known to be a potent pro-resolving lipid mediator
      that prevents chronic inflammation and osteoclastogenesis. We investigated the
      inhibitory effects of RvE1 on osteoclastogenesis and bone resorption to clarify
      its therapeutic potential for rheumatoid arthritis (RA). Methods: Receptor
      activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast
      differentiation was assessed with tartrate-resistant acid phosphatase staining.
      RANKL-induced bone resorption was assessed by the measurement of pit formation
      using calcium phosphate-labeled fluorescent polyanionic molecules in RAW264.7
      cells as osteoclast precursors. The effects of RvE1 on the RANKL-induced mRNA
      expression of osteoclast-specific genes and transcriptional factors such as c-fos
      and nuclear factor of activated T cells c1 (NFATc1) in RAW264.7 cells were
      measured by quantitative real-time PCR. The distribution of NFATc1 induced by
      RANKL was evaluated by immunofluorescence staining in RAW264.7 cells. To analyze
      the mechanism of the inhibitory effect of RvE1 on osteoclastogenesis, we measured
      IL-17-induced RANKL mRNA expression in MC3T3-E1 osteoblast cells treated with
      RvE1 using quantitative real-time PCR and determined the level of prostaglandin
      E2 (PGE2) production by enzyme-linked immunosorbent assay. Results: RvE1
      significantly suppressed RANKL-induced osteoclast differentiation and bone
      resorption. RvE1 inhibited the RANKL-induced mRNA expression of osteoclast
      specific genes along with the transcription factors NFATc1 and c-fos. Moreover,
      NFATc1 translocation from the cytoplasm to the nucleus of RAW264.7 cells was
      suppressed following RvE1 treatment. RvE1 also inhibited IL-17-induced RANKL mRNA
      expression and PGE2 production in MC3T3-E1 cells. Conclusion: RvE1 inhibited
      osteoclastogenesis and bone resorption by suppressing RANKL-induced NFATc1 and c
      fos expression in osteoclasts and IL-17-induced RANKL expression through the
      autocrine action of PGE2 in osteoblasts. Our data suggest RvE1 as a new
      therapeutic target of RA.

PMID- 29599619
TI  - Association of Clinical Features with Human Leukocyte Antigen in Japanese
      Patients with Ulcerative Colitis.
AB  - Background: The human leukocyte antigen (HLA) region has been found to be
      involved in the pathogenesis of inflammatory bowel disease (IBD), which is
      classified into ulcerative colitis (UC) and Crohn's disease (CD), by genome-wide
      association studies. The aim of this study was to confirm whether HLA-alleles
      confer susceptibility to UC and to determine whether HLA-allel1es are associated
      with the clinical phenotypes in Japanese patients with UC. Methods: In this
      study, HLA typing was performed by PCR-sequence-specific oligonucleotides (PCR
      SSO) to confirm the correlation between UC and HLA alleles (for HLA-A, B, DRB1)
      in 45 Japanese UC patients. In addition, whether the HLA alleles are related to
      patient and clinical background characteristics was examined. Results: Overall,
      62.2%, and 66.7% of the 45 UC patients had HLA-B*52 and HLA-DRB1*15,
      respectively. These allele frequencies were significantly higher than in
      previously reported Japanese control persons (P < 0.0001). The frequencies of
      extraintestinal manifestations [odds ratio (OR) = 0.12, P = 0.039] and a history
      of colectomy (OR = 0.18, P = 0.046) were lower in HLA-B*52-positive UC patients
      than in HLA-B*52 negative UC patients. The white blood cell (WBC) count was
      significantly higher in HLA-DRB1*15-positive patients (9430 +/- 4592/MUL) than in
      HLA-DRB1*15-negative patients (6729 +/- 2160/MUL). Thus, HLA-B*52 and DRB1*15
      appear to be associated with disease features and severity in Japanese UC
      patients. Conclusion: These results indicate that HLA-B*52 and DRB1*15 are not
      only associated with overall UC susceptibility, but also with the clinical
      phenotypes in Japanese patients.

PMID- 29599620
TI  - Vanishing Parotid Tumors on MR Imaging.
AB  - Background: Of all parotid gland tumors, only oncocytoma has been reported to
      appear isointense to the parotid gland, namely vanishing, on fat-saturated T2 and
      T1 postcontrast gadolinium-enhanced magnetic resonance imaging (MRI). The purpose
      of this study was to evaluate vanishing of parotid tumors on conventional MRI
      with and/or without postcontrast gadolinium-enhancement and on diffusion weighted
      imaging (DWI). Methods: In 8 of 51 patients, ten parotid gland tumors had
      homogeneously enhanced lesions and were retrospectively analysed. Comparisons of
      signal intensity between those parotid tumors and parotid glands and evaluations
      of vanishing were performed on T1-weighted imaging (T1WI), T2-weighted imaging
      (T2WI), fat-suppressed T2WI (FS-T2WI), postcontrast gadolinium-enhanced T1WI (CE
      T1WI) and fat-suppressed CE-T1WI (FS-CE-T1WI), DWI as well as apparent diffusion
      coefficient (ADC). Results: Ten parotid gland tumors consisted of five Warthin
      tumors, two pleomorphic adenomas, two parotid carcinomas (small cell carcinoma
      and adenoid cystic carcinoma) and one oncocytoma. All tumors showed hypointensity
      on T1WI and hyperintensity on DWI. Nine of ten tumors showed vanishing on the
      other MR sequences. All Warthin tumors showed vanishing on FS-T2WI, FS-CE-T1WI
      and the ADC map. One oncocytoma showed vanishing on FS-T2WI and the ADC map and
      hyperintensity on FS-CE-T1WI. All pleomorphic adenomas showed vanishing on T2WI
      and CE-T1WI. One adenoid cystic carcinoma showed vanishing only on CE-T1WI.
      Conclusion: Vanishing of parotid tumors can be observed not only on FS-T2WI and
      FS-CE-T1WI but also on T2WI, CE-T1WI and ADC mapping.

PMID- 29599621
TI  - Core Values in Nursing Care Based on the Experiences of Nurses Engaged in
      Neonatal Nursing: A Text-mining Approach for Analyzing Reflection Records.
AB  - Background: Strong feelings about and enthusiasm for nursing care are reflected
      in nurses' thoughts and behaviors in clinical practice and affect their
      profession. This study was conducted to identify the characteristics of core
      values in nursing care based on the experiences of nurses engaged in neonatal
      nursing through a process for recognizing the conceptualization of nursing.
      Methods: We conceptualized nursing care in 43 nurses who were involved in
      neonatal nursing using a reflection sheet. We classified descriptions on a sheet
      based on the Three-Staged Recognition scheme and analyzed them using a text
      mining approach. Results: Nurses involved in neonatal nursing recognized that
      they must take care of the "child," "mother," and "family." Important elements of
      nursing in nurses with less than 5 years versus 5 or more years of neonatal
      nursing experience were classified into seven clusters, respectively. These
      elements were mainly related to family members in both groups. In nurses with
      less than 5 years of experience, four clusters of one-way communication by nurses
      were observed in the analysis of the key elements in nursing. On the other hand,
      five clusters of mutual relationships between patients, their family members, and
      nurses were observed in nurses with 5 or more years of experience. Conclusion: In
      conclusion, the core value of nurses engaged in neonatal nursing is family
      oriented nursing. Nurses with 5 or more years of neonatal nursing experience
      understand patients and their family members well through establishing
      relationships and providing comfort and safety while taking care of them.

PMID- 29599622
TI  - Sample Entropy in Electrocardiogram During Atrial Fibrillation.
AB  - Background: Atrial fibrillation (AF) is an arrhythmia commonly encountered in
      clinical practice. There is a high risk of thromboembolism in patients with AF.
      Nonlinear analyses such as electroencephalogram (EEG), electrocardiogram (ECG),
      and respiratory movement have been used to quantify biological signals, and
      sample entropy (SampEn) has been employed as a statistical measure to evaluate
      complex systems. In this study, we examined the values of SampEn in ECG signals
      for patients with and without AF to measure the regularity and complexity.
      Methods: ECG signals of lead II were recorded from 34 subjects without arrhythmia
      and 15 patients with chronic AF in a supine position. The ECG signals were
      converted into time-series data and SampEn was calculated. Results: The SampEn
      values for the group without arrhythmia were 0.252 +/- 0.114 [time lag (tau) = 1]
      and 0.533 +/- 0.163 (tau = 5), and those for the chronic AF group were 0.392 +/-
      0.158 (tau = 1) and 0.759 +/- 0.246 (tau = 5). The values of SampEn were
      significantly higher in the group with chronic AF than in the group without
      arrhythmia (P < 0.01 for tau = 1, P < 0.004 for tau = 5). The constructed three
      dimensional vectors were plotted in time-delayed three-dimensional space. We used
      time lags of tau = 5 and tau = 1. The shape of the loops of the three-dimensional
      space was better for tau = 5. Conclusion: The values of SampEn from ECG for
      chronic AF patients were higher than for subjects without arrhythmia, suggesting
      greater complexity for the time-series from chronic AF patients. SampEn is
      considered a new index for evaluating complex systems in ECG.

PMID- 29599623
TI  - Comparison of Prognostic Indices in Japanese Patients with Diffuse Large B-cell
      Lymphoma in the Yonago Area.
AB  - Background: Several prognostic indices for diffuse large B-cell lymphoma (DLBCL)
      have been developed. Which index is appropriate for Japanese patients with DLBCL
      treated in real-world practice is unknown. Methods: The prognostic performances
      of the original international prognostic index (IPI), age-adjusted IPI, National
      Comprehensive Cancer Network-IPI, elderly IPI and revised IPI were compared using
      patients with DLBCL treated in a single institute in the Yonago area in Japan.
      Results: From 2005 through 2015, 182 patients with de novo DLBCL were treated
      with chemotherapy in Tottori University Hospital; 154 (85%) patients received R
      CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone)
      although full dose was administered in 63 (35%) patients. The median age of the
      patients was 71 years (range 18 to 91). Three-year overall survival rate was
      71.8% (95% CI, 64.1% to 78.2%). All indices significantly discriminate risk
      groups for overall survival of the patients (P < 0.001). Although no statistical
      difference of performance was found among these indices, the best scores of model
      fit/discrimination measures were beaten out by age-adjusted IPI, the simplest and
      three-factor model. Conclusion: Age-adjusted IPI is still usable in real-world
      practice while a better predictive model is desired for Japanese patients with
      DLBCL.

PMID- 29599624
TI  - Histological Evaluation of Lumbar Spine Changes in Rats with Collagen-induced
      Arthritis.
AB  - Background: To histologically evaluate lumbar involvement in rheumatoid arthritis
      (RA) by investigating rats with collagen-induced arthritis (CIA) and to assess
      the potential effects of RA on the discovertebral joints and facet joints.
      Methods: Seven-month-old female Sprague-Dawley rats were divided into groups with
      CIA and without CIA (control). All rats were sacrificed at 8 weeks after initial
      sensitization and the lumbar spine (L5/6) was harvested. Then the lumbar spine
      block specimens were stained with Villaneuva bone stain and sectioned in the
      midsagittal plane. The left facet joints were also sectioned in the midaxial
      plane. Specimens were studied under a microscope and infiltration of inflammatory
      cells was investigated. Results: In the CIA group, lumbar lesions were observed
      in 13/18 rats (76%). Lymphocytes infiltrated into the anterior rim of the
      vertebral bodies only in 2 rats, while lymphocytes infiltrated the facet joints
      only in 4 rats. Both sites were involved in 7 rats. In addition, osteoclasts
      invaded the anterior rim of the vertebral bodies and formed cavities that also
      contained lymphocytes. Formation of pannus was seen in the facet joints in 11/18
      rats. Conclusion: In CIA rats, infiltration of inflammatory cells into the
      anterior rim of the vertebral bodies alone or into the facet joints alone was
      demonstrated in 2 rats and 4 rats, respectively, while both sites were involved
      in 7 rats. Therefore, lesions at the anterior rim of the vertebral body did not
      arise secondary to facet joint involvement, but were caused by CIA along with
      synovial lesions of the facet joints.

PMID- 29599625
TI  - Postoperative Serum Albumin is a Potential Prognostic Factor for Older Patients
      with Gastric Cancer.
AB  - Background: The incidence of gastric cancer (GC) among older adults is
      increasing. Therefore, determining postoperative age-associated prognostic
      factors is clinically important. This study retrospectively investigated the
      prognostic significance of serum albumin level in older GC patients. Methods: We
      enrolled 135 patients aged >= 75 years, who underwent gastrectomies with
      histopathological diagnoses of gastric adenocarcinoma. Results: Preoperative
      albumin (pre-Alb) levels in patients with advanced GC and stage III/IV GC were
      significantly lower than those in patients with early GC (P = 0.0032) and stage
      I/II GC (P = 0.006), respectively. Postoperative albumin (post-Alb) levels
      (measured 1 month after surgery) in male patients and in patients with advanced
      GC were significantly lower than those in female patients (P = 0.024) and those
      with early GC (P = 0.044), respectively. Post-Alb levels of patients who died of
      other diseases were significantly lower than those who were still living (P =
      0.0004). Prognosis of patients with high post-Alb levels (>= 4g/dL) was
      significantly better than that of patients with low post-Alb levels (< 4g/dL; P =
      0.045); and in multivariate analysis, post-Alb level was an independent
      prognostic indicator. Conclusion: Post-Alb level is a useful predictive factor
      for the prognosis of older GC patients. Postoperative nutritional support might
      help improve the prognosis of older GC patients.

PMID- 29599626
TI  - Benign Sebaceous Epithelioma with Carcinoid-like Trabecular Cell Arrangement.
AB  - A case of 75-year-old woman with sebaceous epithelioma was reported. The
      histological features were distinct in that it had a sinusoidal and carcinoid
      like growth pattern, which has been reported in its malignant counterpart.
      Immunostaining for adipophilin was positive in the area with lipid-laden
      vacuolated cells, but the rest of tumor, which had cord-like nests, was negative.
      MIB index was 2%. CK5/6 and p40 were positive in the cord-like nesting areas.
      CK7, CK20, alpha SMA, and epithelial membrane antigen were negative in both the
      cord-like nesting areas and the adipose-like areas. The tumor was diagnosed as
      sebaceous epithelioma with a trabecular pattern. Dermatopathologists should be
      aware of this atypical histological pattern of benign sebaceous epithelioma.

PMID- 29599627
TI  - Small Bowel Obstruction Due to Mochi (Rice Cake): A Case Report and Review of the
      Literature.
AB  - A 66-year-old man presented at our emergency department with severe intermittent
      abdominal pain. His history revealed that he had eaten several mochi (rice cakes)
      without sufficiently chewing them before swallowing. Following computed
      tomography that showed a high value, he was diagnosed with an obstruction caused
      by mochi. Although mochi obstruction can sometimes improve with conservative
      treatment, this case required laparotomy. Medical literature in English on small
      bowel obstruction due to mochi is rare, but fortunately in this case we were able
      to collect complete laboratory and imaging data. Furthermore, due to the surgical
      findings, we could clearly diagnose the pathophysiology of mochi obstruction.
      Here we describe a case of small bowel obstruction due to mochi, and review the
      literature to determine the characteristics of intestinal obstruction caused by
      it.

PMID- 29599628
TI  - Analysis of Acute Transfusion Reactions and Their Occurrence Times.
AB  - Acute transfusion reactions (ATRs) are significantly relevant to the morbidity
      and mortality of patients. ATRs are mostly not severe and rarely cause severe
      conditions, including anaphylactic shock. The aim of this study was to clarify
      the frequency of ATRs and the time of event occurrence. A total of 18,745
      transfusions were administered to 11,718 patients during a 3-year period. Adverse
      reactions including at least one sign or symptom were collected through a report
      system in 143 of 2,478 (5.7%) platelet concentrate transfusions, 105 of 6,629
      (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen
      plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse
      events. Severe signs and symptoms were observed in 7.1% of patients. These events
      appeared significantly earlier than those of non-severe signs and symptoms
      (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive
      transfusion-associated adverse events, preventive treatments for adverse events
      should be proactively promoted.

PMID- 29599629
TI  - The First Awake Clipping of a Brain Aneurysm in Malaysia and in ASEAN: Achieving
      International Standards.
AB  - World-renowned neurosurgeon, Professor Saleem Abdulrauf, has been featured in
      several medical journals for his successful "Awake Brain Aneurysm Surgery".
      Regarded as a "world first", this surgery, involves clipping un-ruptured brain
      aneurysms while patients are awake. Only one or two neurosurgery centres
      worldwide are capable of this. Performing the surgery while the patient is awake
      lowers risks of brain ischemia with neurological deficits and ventilator
      associated morbidities. The technique has been viewed as the start of a new era
      in brain surgery. Physicians from the Universiti Sains Malaysia (USM) School of
      Medical Sciences, at the Health Campus in Kelantan, headed by Professor Dr
      Zamzuri Idris (neurosurgeon) and Dr Wan Mohd Nazaruddin Wan Hassan
      (neuroanaesthetist), recently performed a similar procedure, the first such
      surgery in Malaysia and Southeast Asia. The USM team can therefore be considered
      to be among the first few to have done this brain surgery and achieved successful
      patient outcomes.

PMID- 29599630
TI  - Potential Benefits of Annona muricata in Combating Cancer: A Review.
AB  - The incidence of cancer is increasing each year, which generates concerns
      regarding the efficacy of the current treatment options. This has caused patients
      to seek alternatives to complement or to replace surgery, chemotherapy and
      radiotherapy. Annona muricata and other plants have been shown to have promising
      compounds that can be utilised in the treatment of cancer. Native to the tropical
      and subtropical parts of the world, A. muricata plant extracts contain compounds
      that are particularly effective against cancer cells. In light of increasing
      concerns regarding the limitations of cancer treatment in hospitals, this review
      attempts to highlight the benefits of A. muricata and its potential to be
      integrated as one of the treatment options against cancer.

PMID- 29599631
TI  - The Effect of Amygdalin on Endoplasmic Reticulum (ER) Stress Induced Hepatic
      Steatosis in Mice.
AB  - Background: Endoplasmic reticulum (ER) stress creates abnormalities in the
      insulin action, inflammatory responses, lipoprotein B100 degradation, and hepatic
      lipogenesis. Hepatic steatosis leads to a broad spectrum of hepatic disorders
      such as nonalcoholic fatty liver disease (NAFLD) and NASH. Amygdalin has
      beneficial effects on asthma, bronchitis, diabetes, and atherosclerosis. We
      designed this study to evaluate the effect of amygdalin on the ER stress induced
      hepatic steatosis. Methods: Inbred mice received saline, DMSO and amygdalin, as
      control groups. ER stress was induced by tunicamycin (TM) injection. Amygdalin
      was administered 1 h before the TM challenge (Amy + TM group). Mice body and
      liver weights were measured. Hematoxylin and eosin (H&E) and oil red O staining
      from liver tissue, were performed. Alanin aminotransferase (ALT), aspartate
      aminotransferase (AST), triglyceride and cholesterol levels were measured.
      Results: Histological evaluation revealed that amygdalin was unable to decrease
      the TM induced liver steatosis; however, ALT and AST levels decreased [ALT:
      35.33(2.15) U/L versus 92.33(6.66) U/L; (57.000, (50.63, 63.36), P < 0.001) and
      AST: 93(5.09) U/L versus 345(97.3) U/L, (252, (163.37, 340.62), P < 0.001)].
      Amygdalin also decreased triglyceride and cholesterol plasma levels in the Amy +
      TM group [TG: 42.66(2.15) versus 53.33(7.24) mg/dL; (10.67, (3.80, 17.54), P =
      0.006) and TC: 9.33(3.55) versus 112.66(4.31) mg/dL, (103.33, (98.25, 108.40) P <
      0.001)]. Conclusion: Amygdalin improved the ALT, AST, and lipid serum levels
      after the TM challenge; however, it could not attenuate hepatic steatosis.

PMID- 29599632
TI  - Comparison of the Effects of Dexmedetomidine on the Induction of Anaesthesia
      Using Marsh and Schnider Pharmacokinetic Models of Propofol Target-Controlled
      Infusion.
AB  - Background: The study aimed to determine the effects of dexmedetomidine on the
      induction of anaesthesia using different models (Marsh and Schnider) of propofol
      target-controlled infusion (TCI). Methods: Sixty-four patients aged 18-60 years,
      American Society of Anaesthesiologists (ASA) class I-II who underwent elective
      surgery were randomised to a Marsh group (n = 32) or Schnider group (n = 32). All
      the patients received a 1 MUg/kg loading dose of dexmedetomidine, followed by TCI
      anaesthesia with remifentanil at 2 ng/mL. After the effect-site concentration
      (Ce) of remifentanil reached 2 ng/mL, propofol TCI induction was started.
      Anaesthesia induction commenced in the Marsh group at a target plasma
      concentration (Cpt) of 2 MUg/mL, whereas it started in the Schnider group at a
      target effect-site concentration (Cet) of 2 MUg/mL. If induction was delayed
      after 3 min, the target concentration (Ct) was gradually increased to 0.5 MUg/mL
      every 30 sec until successful induction. The Ct at successful induction,
      induction time, Ce at successful induction and haemodynamic parameters were
      recorded. Results: The Ct for successful induction in the Schnider group was
      significantly lower than in the Marsh group (3.48 [0.90] versus 4.02 [0.67]
      MUg/mL; P = 0.01). The induction time was also shorter in the Schnider group as
      compared with the Marsh group (134.96 [50.91] versus 161.59 [39.64]) sec; P =
      0.02). There were no significant differences in haemodynamic parameters and Ce at
      successful induction. Conclusion: In the between-group comparison,
      dexmedetomidine reduced the Ct requirement for induction and shortened the
      induction time in the Schnider group. The inclusion of baseline groups without
      dexmedetomidine in a four-arm comparison of the two models would enhance the
      validity of the findings.

PMID- 29599633
TI  - The Factors Associated with Outcomes in Surgically Managed Ruptured Cerebral
      Aneurysm.
AB  - Background: Ruptured cerebral aneurysm is a life-threatening condition that
      requires urgent medical attention. In Malaysia, a prospective study by the Umum
      Sarawak Hospital, Neurosurgical Center, in the year 2000-2002 revealed an average
      of two cases of intracranial aneurysms per month with an operative mortality of
      20% and management mortality of 25%. Failure to diagnose, delay in admission to a
      neurosurgical centre, and lack of facilities could have led to the poor surgical
      outcome in these patients. The purpose of this study is to identify the factors
      that significantly predict the outcome of patients undergoing a surgical clipping
      of ruptured aneurysm in the local population. Material and Method: A single
      center retrospective study with a review of medical records was performed
      involving 105 patients, who were surgically treated for ruptured intracranial
      aneurysms in the Sultanah Aminah Hospital, in Johor Bahru, from July 2011 to
      January 2016. Information collected was the patient demographic data, Glasgow
      Coma Scale (GCS) prior to surgery, World Federation of Neurosurgical Societies
      Scale (WFNS), subarachnoid hemorrhage (SAH) grading system, and timing between
      SAH ictus and surgery. A good clinical grade was defined as WFNS grade I-III,
      whereas, WFNS grades IV and V were considered to be poor grades. The outcomes at
      discharge and six months post surgery were assessed using the modified Rankin's
      Scale (mRS). The mRS scores of 0 to 2 were grouped into the "favourable" category
      and mRS scores of 3 to 6 were grouped into the "unfavourable" category. Only
      cases of proven ruptured aneurysmal SAH involving anterior circulation that
      underwent surgical clipping were included in the study. The data collected was
      analysed using the Statistical Package for Social Sciences (SPSS). Univariate and
      multivariate analyses were performed and a P-value of < 0.05 was considered to be
      statistically significant. Result: A total of 105 patients were included. The
      group was comprised of 42.9% male and 57.1% female patients. The mean GCS of the
      patients subjected to surgical clipping was 13, with the majority falling into
      the good clinical grade (78.1%). The mean timing of the surgery after SAH was 5.3
      days and this was further categorised into early (day one to day three, 45.3%),
      intermediate (day four to day ten, 56.2%), and late (after day ten, 9.5%). The
      total favourable outcome achieved at discharge was 59.0% as compared to 41.0% of
      the unfavourable outcome, with an overall mortality rate of 10.5%. At the six
      month post surgery review (n = 94), the patients with a favourable outcome
      constituted 71.3% as compared to 28.7% with an unfavourable outcome. The
      mortality, six months post surgery was 3.2%. On a univariate analysis of early
      surgical clipping, patients with a better GCS and good clinical grade had a
      significantly better outcome at discharge. Based on the univariate study, six
      months post surgery, the timing of the surgery and the clinical grade remained
      significant predictors of the outcome. On the basis of the multivariate analysis,
      male patients of younger age, with a good clinical grade, were associated with
      favourable outcomes, both at discharge and six months post surgery. Conclusion:
      In this study, we concluded that younger male patients with a good clinical grade
      were associated with a favourable outcome both at discharge and six months post
      surgery. We did not find the timing of the surgery, size of the aneurysm or
      duration of surgery to be associated with a patient's surgical outcome.
      Increasing age was not associated with the surgical outcome in a longer term of
      patient's follow up.

PMID- 29599634
TI  - Association of Co-Morbidity and Treatment with the Complications of Acute
      Coronary Syndrome in Young Patients Less Than 45 Years.
AB  - Background: Approximately 5%-10% of acute coronary syndrome (ACS) cases occur in
      people younger than 45 years of age. This study aimed to identify complications
      of ACS and the associated factors in young patients. Methods: In this cross
      sectional study, data from 147 ACS patients aged less than 45 years were
      analysed. Results: The mean age was 39.1 (4.9) years, the male to female ratio
      was 3:1; 21.2% of patients presented with unstable angina, 58.5% had non-ST
      elevation myocardial infarction and 20.4% had ST elevation myocardial infarction.
      The most frequent risk factor of ACS was dyslipidaemia (65.3%), followed by
      hypertension (43.5%). In total, 49.7% of patients had inpatient complication(s),
      with the most common being heart failure (35.4%), followed by arrhythmia (20.4%).
      The significant factors associated with ACS complications were current smoking
      [adjusted odds ratio (AOR) 4.03; 95% confidence interval (CI): 1.33, 12.23; P
      value = 0.014], diabetic mellitus [AOR 3.03; 95% CI: 1.19, 7.71; P-value =
      0.020], treatments of fondaparinux [AOR 0.18; 95% CI: 0.08, 0.39; P-value <
      0.001] and oral nitrates [AOR 0.18; 95% CI: 0.08, 0.42; P-value < 0.001].
      Conclusions: Smoking status and diabetes mellitus were modifiable risk factors
      while pharmacological treatment was an important protective factor for ACS
      complications in young patients.

PMID- 29599635
TI  - The Effectiveness of Breastfeeding Intervention on Breastfeeding Exclusivity and
      Duration among Primiparous Mothers in Hospital Universiti Sains Malaysia.
AB  - Background: In Malaysia, the rates of mothers practising breastfeeding
      exclusively among babies at six months of age still do not achieve the Global
      Nutritional Targets 2025 which is 50%. Objective: To determine the effectiveness
      of breastfeeding intervention in improving breastfeeding outcomes. Method: A
      quasi-experimental design was used involving a purposive sample of 96
      primigravidas (intervention group (IG) = 48, control group (CG) = 48) recruited
      at Hospital USM. Data were collected using the Breastfeeding Assessment
      Questionnaire. Mothers in IG received the current usual care and two hours of an
      additional education programme on breastfeeding, breastfeeding booklet, notes
      from the module, and postnatal breastfeeding support in the first week of
      postpartum. Mothers in CG received the current usual care only. The mothers were
      assessed on the first and sixth week and then the fourth and sixth month of
      postpartum. Results: The results indicated that there was a statistically
      significant difference between the groups on the fourth month postpartum (X2 =
      5.671, P = 0.017) in practicing full breastfeeding. The breastfeeding duration
      rates of the IG were longer than those of the CG. However, the results showed
      only two follow-up weeks that were significant (week 6, X2 = 5.414, P = 0.020,
      month 4, X2 = 7.515, P = 0.006). There was a statistically significant difference
      between IG and CG as determined by one-way ANCOVA on the breastfeeding duration
      after controlling age and occupation, F (3, 82) = 6.7, P = 0.011. The test
      revealed that the breastfeeding duration among IG was significantly higher (20.80
      +/- 6.31) compared to CG (16.98 +/- 8.97). Conclusions: Breastfeeding
      intervention can effectively increase breastfeeding duration and exclusivity
      outcomes among primiparous mothers.

PMID- 29599636
TI  - The Influence of Audio-Visual Cueing (Traffic Light) on Dual Task Walking in
      Healthy Older Adults and Older Adults with Balance Impairments.
AB  - Background: The walking gait of older adults with balance impairment is affected
      by dual tasking. Several studies have shown that external cues can stimulate
      improvement in older adults' performance. There is, however, no current evidence
      to support the usefulness of external cues, such as audio-visual cueing, in dual
      task walking in older adults. Thus, the aim of this study was to investigate the
      influence of an audio-visual cue (simulated traffic light) on dual task walking
      in healthy older adults and in older adults with balance impairments. Methods: A
      two-way repeated measures study was conducted on 14 healthy older adults and 14
      older adults with balance impairment, who were recruited from the community in
      Chiang Rai, Thailand. Their walking performance was assessed using a four-metre
      walking test at their preferred gait speed and while walking under two further
      gait conditions, in randomised order: dual task walking and dual task walking
      with a simulated traffic light. Each participant was tested individually, with
      the testing taking between 15 and 20 minutes to perform, including two-minute
      rest periods between walking conditions. Two Kinect cameras recorded the spatio
      temporal parameters using MFU gait analysis software. Each participant was tested
      for each condition twice. The mean parameters for each condition were analysed
      using a two-way repeated measures analysis of variance (ANOVA) with participant
      group and gait condition as factors. Result: There was no significant between
      group effect for walking speed, stride length and cadence. There were also no
      significant effects between gait condition and stride length or cadence. However,
      the effect between gait condition and walking speed was found to be significant
      [F(1.557, 40.485) = 4.568, P = 0.024, [Formula: see text]]. Conclusion: An audio
      visual cue (simulated traffic light) was found to influence walking speed in both
      healthy older adults and in older adults with balance impairment. The results
      suggest that audio-visual cues could be incorporated into healthy lifestyle
      promotion in older adults with balance impairment.

PMID- 29599637
TI  - Undergraduate Medical Students' Perceptions on Feedback-Seeking Behaviour.
AB  - Background: The concept of feedback-seeking behaviour has been widely studied,
      but there is still a lack of understanding of this phenomenon, specifically in an
      Indonesian medical education setting. The aim of this research was to investigate
      medical students' feedback-seeking behaviour in depth in one Indonesian medical
      school. Methods: A qualitative method was employed to explore the feedback
      seeking behaviour of undergraduate medical students in the Faculty of Medicine at
      Universitas Lampung. Focus group discussions (FGDs) were conducted with four
      student groups and each group consisted of 7-10 students from the years 2012,
      2013 and 2014. Data triangulation was carried out through FGDs with teaching
      staff, and an interview with the Head of the Medical Education Unit. Results:
      Study findings indicated that the motivation of students to seek feedback was
      underlain by the desire to obtain useful information and to control the
      impressions of others. Students will tend to seek feedback from someone to whom
      they have either a close relationship or whose credibility they value. The most
      common obstacle for students to seek feedback is the reluctance and fearfulness
      of receiving negative comments. Conclusions: Through the identification of
      factors promoting and inhibiting feedback-seeking behaviour, medical education
      institutions are enabled to implement the appropriate and necessary measures to
      create a supportive feedback atmosphere in the learning process.

PMID- 29599638
TI  - Clinical and Sociodemographic Predictors of the Quality of Life among Patients
      with Type 2 Diabetes Mellitus on the East Coast of Peninsular Malaysia.
AB  - Background: The quality of life (QoL) describes the multidimensional self
      perceived well-being of a person, which is an important diabetes outcome. This
      study aimed to measure the QoL scores among patients with type 2 diabetes
      mellitus (T2DM), as well as their clinical and sociodemographic predictors.
      Methods: This cross-sectional study involved 180 randomly sampled patients at a
      primary care clinic on the East Coast of Peninsular Malaysia. A self-administered
      questionnaire containing the Audit of Diabetes Dependent Quality of Life-18
      (ADDQoL-18) was used. Results: Most of the respondents (96.7%) were Malay, with a
      median (interquartile range, IQR) age of 54.0 (14.0) years old. The majority of
      them were females (60.0%), married (81.1%) and from low-income families (63.3%),
      who attained a secondary education or lower (75.6%). Only 49.4% of them were
      employed. The mean (standard deviation, SD) ADDQoL-18 average weighted impact
      score was -4.58 (2.21) and all 18 domains were negatively affected, particularly
      the living condition, family life and working life. The multiple linear
      regression analysis showed that the age (adjusted B = 0.05, P = 0.004) and
      insulin use (adjusted B = -0.84, P = 0.011) were QoL predictors. Conclusion: T2DM
      negatively impacts the patient's QoL in all aspects of their life. The QoL
      improvement with age suggests that the older patients had accepted and adapted to
      their illness. The need to improve the QoL among insulin users was also
      highlighted.

PMID- 29599639
TI  - Association of Well-Being Index and Cognitive Impairment with Primary Open Angle
      Glaucoma Patients of Malaysia: A Case-Control Study.
AB  - The purpose of this study was to determine the association of well-being and
      cognitive impairment with primary open angle glaucoma (POAG) patients attending a
      tertiary care hospital in Malaysia. Fifty-four individuals were recruited for
      study as cases were matched with 60 individuals as the control subjects, and data
      were collected using the WHO well-being index and the validated 6-item cognitive
      impairment test dementia test. The results showed that there was no significant
      association between gender, ethnicity, socioeconomic status and POAG. Patients
      with POAG had significantly lower well-being index scores (mean 67.93) than the
      control group (mean 81.60) with P-value < 0.001. Similarly, patients with POAG
      had a significantly higher score of cognitive impairment (CIT test) (mean 6.15)
      compared to the control group (mean 0.40) with P-value < 0.001. Consequently,
      POAG is likely to be associated with higher cognitive impairment and lower well
      being index.

PMID- 29599641
TI  - Large Solitary Pulmonary Cryptococcoma Mimicking Lung Carcinoma in an
      Immunocompetent Patient.
AB  - Cryptococcosis is a life-threatening mycosis typically seen in immunocompromised
      patients. Pulmonary cryptococcosis generally presents as multiple or solitary
      nodular opacities. Cryptococcal infection presenting as a destructing cavernoma
      (cryptococcoma) without diffuse infiltration of the lung is an extremely rare
      presentation, even in immunocompromised patients. This report presents a healthy,
      HIV negative, immunocompetent patient who presented with a large solitary lung
      mass provisionally diagnosed as a lung malignancy on radiological imaging that
      proved to be a large cryptococcoma after biopsy. The patient was treated with
      liposomal Amphotericin B and fluconazole, and the lesion showed regression on
      serial imaging. This case report thus highlights an unconventional presentation
      of pulmonary cryptococcosis in an immunocompetent individual.

PMID- 29599642
TI  - Let's Say Good-Bye to Obesity: More the Chicken (Antibiotic-Treated) in Kitchen,
      More the Obesity Risk.

PMID- 29599640
TI  - The Effects of 4-Hydroxybenzoic Acid Identified from Bamboo (Dendrocalamus asper)
      Shoots on Kv1.4 Channel.
AB  - Background: Bamboo shoot has been used as a treatment for epilepsy in traditional
      Chinese medicine for generations to treat neuronal disorders such as convulsive,
      dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol
      found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and
      apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the
      voltage-gated potassium channels with two inactivation mechanisms; the fast N
      type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation
      and signaling the restoration of resting membrane potential through the
      regulation of the movement of K+ across the cellular membrane. Methods: Chemical
      compounds from Dendrocalamus asper bamboo shoots were purified and identified as
      major palmitic acids mixed with other minor fatty acids, palmitic acid, 4
      hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one.
      The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium
      channel which was injected into viable oocytes that was extracted from Xenopus
      laevis. The current were detected by the two-microelectrode voltage clamp,
      holding potential starting from -80 mV with 20 mV step-up until +80 mV. Readings
      of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were
      taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of
      the Kv1.4 channels with n >= 6 (number of oocytes tested). The decreases of the
      ratios of five different concentrations (1 MUM, 10 MUM, 100 MUM, 1 mM and 2.5 mM)
      were compared with 0.1% DMSO as the control. Results: All concentration showed
      statistically significant results with P < 0.05 except for 100 MUM. The
      normalised current of the 4-hba concentrations were compared with potassium
      channel blockers (TEA and 4-AP) and all groups showed statistically significant
      results. This study also showed that time taken for each concentration to affect
      Kv1.4 does not play any significant roles. Conclusion: 4-hydroxybenzoic acid was
      found to be able to enhance the inactivation of Kv1.4 by lowering the membrane
      potential so that the abnormal neuronal firing can be inhibited. With IC50
      slightly higher than 10 MUM, increasing concentrations (100 MUM, 1 mM and 2.5 mM)
      had shown to exhibit toxicity effects. The best concentration from this study is
      10 MUM with Hill slope of 0.1799.

PMID- 29599643
TI  - LAMP Method as One of the Best Candidates for Replacing with PCR Method.

PMID- 29599644
TI  - Does space-time torsion determine the minimum mass of gravitating particles?
AB  - We derive upper and lower limits for the mass-radius ratio of spin-fluid spheres
      in Einstein-Cartan theory, with matter satisfying a linear barotropic equation of
      state, and in the presence of a cosmological constant. Adopting a spherically
      symmetric interior geometry, we obtain the generalized continuity and Tolman
      Oppenheimer-Volkoff equations for a Weyssenhoff spin fluid in hydrostatic
      equilibrium, expressed in terms of the effective mass, density and pressure, all
      of which contain additional contributions from the spin. The generalized Buchdahl
      inequality, which remains valid at any point in the interior, is obtained, and
      general theoretical limits for the maximum and minimum mass-radius ratios are
      derived. As an application of our results we obtain gravitational red shift
      bounds for compact spin-fluid objects, which may (in principle) be used for
      observational tests of Einstein-Cartan theory in an astrophysical context. We
      also briefly consider applications of the torsion-induced minimum mass to the
      spin-generalized strong gravity model for baryons/mesons, and show that the
      existence of quantum spin imposes a lower bound for spinning particles, which
      almost exactly reproduces the electron mass.

PMID- 29599645
TI  - What if gravity becomes really repulsive in the future?
AB  - The current acceleration of the Universe is one of the most puzzling issues in
      theoretical physics nowadays. We are far from giving an answer in this letter to
      the question of its nature. Yet, with the observations we have at hand, we
      analyse the different patterns that the gravitational potential can show in the
      future. Surprisingly, gravity not only can get weaker in the near future, it can
      even become repulsive; or equivalently, the gravitational potential may become
      negative. We show this remark by using one of the simplest phenomenological model
      we can imagine for dark energy. We have also reviewed the statefinder approach of
      these models. For completeness, we have also showed the behaviour of the density
      contrast of dark matter and dark energy for these simple (yet illustrative
      models). Our results are displayed and we see how they shall evolve in the
      future.

PMID- 29599646
TI  - lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage
      Polarization.
AB  - The innate immune system is the first line of defense against microbial
      pathogens. The activated innate immune system plays important roles in eliciting
      antimicrobial defenses. Despite the benefits of innate immune responses,
      excessive inflammation will cause host damage. Thus, tight regulation of these
      processes is required for the maintenance of immune homeostasis. Recently, a new
      class of long noncoding RNAs (lncRNAs) has emerged as important regulators in
      many physiological and pathological processes. Dysregulated lncRNAs have been
      found to be associated with excessive or uncontrolled inflammation. In this brief
      review, we summarize the roles of functional lncRNAs in regulating innate immune
      responses. We also discuss the roles of lncRNAs in macrophage polarization, an
      important molecular event in the innate immune responses.

PMID- 29599647
TI  - Prognostic value of long non-coding RNA BLACAT1 in patients with papillary
      thyroid carcinoma.
AB  - Background: Long noncoding RNAs (lncRNAs) have been reported to have potential
      diagnostic and prognostic values for numerous cancers. However, the plasma
      expression of lncRNA BLACAT1 and its clinical value in patients with papillary
      thyroid cancer (PTC) remain unknown. Methods: The expression profile of BLACAT1
      in 87 PTC patients (case group) and 36 patients with nodular goiter (control
      group) were investigated by qRT-PCR. The Kaplan-Meier method was used for RFS
      curves, and the univariate survival differences were analyzed by the log-rank
      test. Results: BLACAT1 expression was downregulated in the plasma of case group
      compared with control group (P = 0.003). We also found that low plasma BLACAT1
      expression was correlated with lymph node metastasis (LNM) (P < 0.001).
      Multivariate analysis showed that BLACAT1 was an independent risk factor for
      lymph node metastasis and gender (P < 0.05). The area under the ROC curve for
      BLACAT1 was 0.825 in LNM prediction (P < 0.001). Conclusion: The present study
      demonstrated that BLACAT1 could act as a possible suppressor gene in PTC and may
      serve as a potential biomarker for prognosis prediction of PTC.

PMID- 29599648
TI  - Masculine Discrepancy Stress and Psychosocial Maladjustment: Implications for
      Behavioral and Mental Health of Adolescent Boys.
AB  - Gender role discrepancy (GRD), or nonconformity to socially prescribed gender
      roles, has been linked to a multitude of adverse mental and behavioral health
      outcomes. Masculine discrepancy stress (MDS), stress about being perceived not to
      conform to one's gender role, may explain the relationship between GRD and
      deleterious health outcomes. However, research on MDS has primarily been
      restricted to adult males. This leaves a critical gap pertaining to the potential
      effect of MDS on adolescent boys, who may be more malleable and susceptible to
      the influence and pressures of gender socialization. In the current study, data
      are drawn from a sample of adolescent male students (N = 592) who completed self
      report questionnaires. We employed structural equation modeling to test the
      effects of GRD and MDS on psychosocial maladjustment measured via sexual
      behavior, substance use, violence, mood disorder symptoms, and hopelessness. In
      addition, we controlled for critical risk factors including sociodemographic
      characteristics, adverse childhood experiences, trauma symptoms, and neighborhood
      disorganization. Findings indicate significant potentiating effects of MDS on
      maladjustment while there were direct protective effects of GRD. These data
      suggest that developing prevention strategies that incorporate social norms
      pertaining to gender socialization may have an impact on multiple behavioral and
      mental health problems.

PMID- 29599649
TI  - SnapVX: A Network-Based Convex Optimization Solver.
AB  - SnapVX is a high-performance solver for convex optimization problems defined on
      networks. For problems of this form, SnapVX provides a fast and scalable solution
      with guaranteed global convergence. It combines the capabilities of two open
      source software packages: Snap.py and CVXPY. Snap.py is a large scale graph
      processing library, and CVXPY provides a general modeling framework for small
      scale subproblems. SnapVX offers a customizable yet easy-to-use Python interface
      with "out-of-the-box" functionality. Based on the Alternating Direction Method of
      Multipliers (ADMM), it is able to efficiently store, analyze, parallelize, and
      solve large optimization problems from a variety of different applications.
      Documentation, examples, and more can be found on the SnapVX website at
      http://snap.stanford.edu/snapvx.

PMID- 29599650
TI  - No Relation between Psoriasis and Renal Abnormalities: A Case-Control Study.
AB  - Multiple observational studies have demonstrated that psoriasis is associated
      with nephropathy; however, the renal involvement in psoriasis remains largely a
      matter of debate. The current study was designed to investigate if psoriatic
      patients are at increased risk of renal abnormalities, in absence of any other
      comorbidities. Forty patients (11 women, 29 men, mean age 44.9 +/- 15.45 years)
      with moderate to severe chronic plaque type psoriasis who were not under systemic
      therapy and 40 age- and gender-matched control subjects were enrolled in the
      study. Patients and controls with history of diabetes, hypertension, and chronic
      renal disease were excluded. Urinalysis by dipstick and microscopic evaluation
      and 24 h proteinuria and albuminuria were measured in all patients and controls.
      Patients with psoriasis and controls were not significantly different with
      respect to the prevalence of abnormal urinalysis (7.5% versus 5%, P = 1.0), mean
      24 h proteinuria (70.40 +/- 24.38 mg/24 h versus 89.40 +/- 26.78 mg/24 h, P =
      0.30), and albuminuria (14.15 +/- 8.12 mg/24 h versus 16.62 +/- 8.21 mg/24 h, P =
      0.18). The presence of abnormal urinalysis was not more common in patients with
      psoriasis than in controls. Our study demonstrated that psoriatic patients
      without any other comorbidities are not at increased risk of kidney disease.

PMID- 29599651
TI  - Mindfulness-Based Interventions in Psychiatry.
AB  - Mindfulness meditation has a longstanding history in eastern practices that has
      received considerable public interest in recent decades. Indeed, the science,
      practice, and implementation of Mindfulness Based Interventions (MBIs) have
      dramatically increased in recent years. At its base, mindfulness is a natural
      human state in which an individual experiences and attends to the present moment.
      Interventions have been developed to train individuals how to incorporate this
      practice into daily life. The current article will discuss the concept of
      mindfulness and describe its implementation in the treatment of psychiatric
      disorders. We further identify for whom MBIs have been shown to be efficacious
      and provide an up-to-date summary of how these interventions work. This includes
      research support for the cognitive, psychological, and neural mechanisms that
      lead to psychiatric improvements. This review provides a basis for incorporating
      these interventions into treatment.

PMID- 29599652
TI  - The Utility of Lumbar Puncture After a Negative Head CT in the Emergency
      Department Evaluation of Subarachnoid Hemorrhage.
AB  - Background: American College of Emergency Physicians (ACEP) [1] recommends that
      patients presenting with acute non-traumatic headache concerning for subarachnoid
      hemorrhage (SAH) undergo lumbar puncture (LP) when non-contrast head computed
      tomography (CT) is negative. The diagnostic yield of this approach is unknown.
      Objective: Evaluate the diagnostic yield, lengths of stay and complication rates
      of LPs in patients undergoing Emergency Department (ED) evaluation for aneurysmal
      SAH. Methods: Multi-center, retrospective, hypothesis-blinded, explicit chart
      review of patients undergoing ED-based lumbar puncture between 2007 and 2012.
      Charts of neurologically intact patients presenting with headache that had a
      negative head CT and underwent LP primarily to rule out SAH were reviewed.
      Trained data abstractors blinded to study hypothesis used standardized data forms
      with predefined terms for chart abstraction. We re-abstracted and assessed inter
      rater agreement for 20 percent of charts with a 100 percent inter-rater
      agreement. Data were descriptive, using 95 percent confidence intervals. Results:
      1,282 LPs were performed, and 342 patients met inclusion criteria but only 1
      percent were deemed positive for SAH in the chart. No aneurysm or vascular
      malformation was identified in those with positive LPs for SAH. Complications
      were in 4 percent and xanthochromia was found in 13 percent. Total length of stay
      was 7.8 hours (0.95 CI; 7.5 - 8.2). No patient discharged from the ED after a
      negative workup for SAH was re-admitted for SAH or underwent a neurosurgical
      procedure during a three-month follow-up period. Conclusions: LP in our cohort of
      neurologically intact CT-negative ED headache patients did not identify any cases
      of aneurysmal SAH but was associated with serious complications, a significant
      false positive rate, and extended ED length of stay.

PMID- 29599653
TI  - Corneal Innervation and Sensation: The Eye and Beyond.
AB  - The cornea is one of the most densely innervated and sensitive tissues in the
      body. In addition to their important sensory functions, corneal nerves induce
      reflex tear production, blinking, and the release of trophic factors - all of
      which combined help to maintain the structural and functional integrity of the
      surface of the eye. Consequently, damage to corneal nerves as a result of
      disease, surgery, or trauma can lead to diminished corneal sensitivity,
      epithelial defects, and possible blindness. In this review, we describe commonly
      used tools that have provided considerable new information on corneal
      architecture and sensation in healthy and diseased corneas, with special emphasis
      on changes seen in herpes zoster ophthalmicus, corneal and other therapeutic
      ocular procedures, antiglaucoma medical therapy, aging, and diabetes. With its
      potential applications ranging from managing ocular-specific to systemic
      diseases, the study of corneal innervation has implications for future therapies
      extending beyond just the eye itself.

PMID- 29599654
TI  - Serotonergic Modulation of Olfaction in Rodents and Insects.
AB  - Recent advances in genetic tools and optical imaging technology have allowed
      rodent and Drosophila researchers to explore the relationship between
      serotonergic modulation and olfactory processing at a mechanistic level
      previously unfeasible. Here, I review the basic organization of olfactory and
      serotonergic systems in both rodents and Drosophila and draw comparisons where
      similarities exist. I discuss circuit level models that explain many of
      serotonin's effects on olfactory responses in the olfactory system's inputs and
      outputs. Finally, I discuss models of integration within wide-field centrifugal
      neurons to emphasize the importance of studying serotonergic neurons directly to
      build more realistic models of olfactory and modulatory interactions.

PMID- 29599655
TI  - Dark Matters: Challenges of Nocturnal Communication Between Plants and Animals in
      Delivery of Pollination Services.
AB  - The night is a special niche characterized by dim light, lower temperatures, and
      higher humidity compared to the day. Several animals have made the transition
      from the day into the night and have acquired unique adaptations to cope with the
      challenges of performing nocturnal activities. Several plant species have opted
      to bloom at night, possibly as a response to aridity to prevent excessive water
      loss through evapotranspiration since flowering is often a water-demanding
      process, or to protect pollen from heat stress. Nocturnal pollinators have visual
      adaptations to function under dim light conditions but may also trade off vision
      against olfaction when they are dependent on nectar-rewarding and scented
      flowers. Nocturnal pollinators may use CO2 and humidity cues emanating from
      freshly-opened flowers as indicators of nectar-rich resources. Some endothermic
      nocturnal insect pollinators are attracted to thermogenic flowers within which
      they remain to obtain heat as a reward to increase their energy budget. This
      review focuses on mechanisms that pollinators use to find flowers at night, and
      the signals that nocturnally blooming flowers may employ to attract pollinators
      under dim light conditions. It also indicates gaps in our knowledge. While
      millions of years of evolutionary time have given pollinators and plants
      solutions to the delivery of pollination services and to the offering of
      appropriate rewards, this history of successful evolution is being threatened by
      artificial light at night. Excessive and inappropriate illumination associated
      with anthropogenic activities has resulted in significant light pollution which
      serves to undermine life processes governed by dim light.

PMID- 29599656
TI  - Degenerative Cervical Myelopathy: A Clinical Review.
AB  - Degenerative Cervical Myelopathy (DCM) is the most common form of spinal cord
      impairment in adults and results in disability and reduced quality of life. DCM
      can present with a wide set of clinical and imaging findings, including: 1) pain
      and reduced range of motion of the neck, and motor and sensory deficits on
      clinical exam, and 2) cord compression due to static and dynamic injury
      mechanisms resulting from degenerative changes of the bone, ligaments, and
      intervertebral discs on MRI. The incidence and prevalence of DCM has been
      estimated at a minimum of 4.1 and 60.5 per 100,000, respectively, but surgical
      trends and an aging population suggest these numbers will rise in the future. The
      diagnosis of DCM is based on clinical examination, with a positive Hoffmann's
      sign and hand numbness typically appearing in the upper limbs, and gait
      abnormalities such as difficulty with tandem gait serving as sensitive diagnostic
      findings. Loss of bladder function may also occur in patients with severe DCM.
      The degree of neurological impairment can be measured using the modified Japanese
      Association Scale (mJOA) or Nurick grade. Non-operative management has a limited
      role in the treatment, while surgical management has been shown to both be safe
      and effective for halting disease progression and improving neurological
      function. Predictors of surgical outcome include age and baseline severity,
      indicating that early recognition of DCM is important for ensuring an optimal
      surgical outcome.

PMID- 29599657
TI  - Phototransduction in Retinal Ganglion Cells.
AB  - The mammalian retina contains a small number of retinal ganglion cells that
      express melanopsin, a retinal based visual pigment, and generate a depolarizing
      response to light in the absence of rod and cone driven synaptic input; hence
      they are referred to as intrinsically photosensitive retinal ganglion cells
      (ipRGCs). They have been shown to be comprised of a number of sub-types and to
      provide luminance information that participates primarily in a variety of non
      imaging forming visual functions. Here I review what is currently known about the
      cascade of events that couple the photoisomerization of melanopsin to the opening
      of a non-selective cation channel. While these events conform in a general sense
      to the prevailing model for invertebrate phototransduction, in which visual
      pigment signals through a G protein of the Gq class and a phospholipase C cascade
      to open a TRPC type ion channel, none of the molecular elements in the melanopsin
      transduction process have been unequivocally identified. This has given rise to
      the possibility that the underlying mechanism responsible for intrinsic
      photosensitivity is not same in all ipRGC sub-types and to the recognition that
      signal transduction in ipRGCs is more complex than originally thought.

PMID- 29599659
TI  - Beyond Sensation: Exploring the Molecular and Genetic Basis for Pain: An
      Interview with Stephen Waxman, MD, PhD.

PMID- 29599658
TI  - Sensory Disruption in Modern Living and the Emergence of Sensory Inequities.
AB  - Modern lifestyles are disrupting the human senses-primarily sight, sound, and
      smell. Noise-induced hearing loss has been noted for centuries and increasing
      over time following the industrial era. From the mid-20th century, the numbers of
      individuals with myopia (the leading visual impairment) have been increasing
      globally. Historical evidence for olfactory dysfunction is not known but its
      etiological links to pollution suggest it increased following industrialization.
      Clinical interventions for sight and sound loss include preventative and
      corrective measures but none exist for olfactory dysfunction. Further, olfactory
      loss is linked to multiple negative health outcomes across physical, mental, and
      social domains. Due to the global rates of exposure to pollution, olfaction is a
      global health concern. The environmental injustice inherent in human society
      (locally and globally) results in inequitable risk for sensory loss by the most
      vulnerable populations and creates an even deeper gradient in health disparity.
      Situated within the environmental justice and health disparity literature, this
      paper introduces the term sensory inequity to describe variation in sensory
      environments based on socio-economic status (which is often entwined with race
      and education). A key challenge to risk management is awareness of sensory
      inequity experienced by vulnerable populations and incorporating that awareness
      into basic research and policy.

PMID- 29599660
TI  - A Career in Addiction Medicine: An Interview with Patrick G. O'Connor, MD, MPH,
      FACP.

PMID- 29599661
TI  - On the Opioid Crisis and the Future of Pain Treatment: An Interview with Bertha
      K. Madras, PhD.

PMID- 29599662
TI  - Automating data citation: the eagle-i experience.
AB  - Data citation is of growing concern for owners of curated databases, who wish to
      give credit to the contributors and curators responsible for portions of the
      dataset and enable the data retrieved by a query to be later examined. While
      several databases specify how data should be cited, they leave it to users to
      manually construct the citations and do not generate them automatically. We
      report our experiences in automating data citation for an RDF dataset called
      eagle-i, and discuss how to generalize this to a citation framework that can work
      across a variety of different types of databases (e.g. relational, XML, and RDF).
      We also describe how a database administrator would use this framework to
      automate citation for a particular dataset.

PMID- 29599663
TI  - Interactive effects of work psychosocial factors on participation in workplace
      wellness programs.
AB  - This study explored concurrent effects of six work psychosocial factors on
      current participation and the self-reported likelihood of future participation in
      workplace wellness programs using a cross-sectional survey, an ad hoc focus
      group, and structured interviews. Classification and regression tree analysis was
      used to analyze survey responses from 343 employees (194 nonparticipants, 95
      participants, and 54 engaged participants). A thematic analysis of focus group (n
      = 7) and interview (n = 5) narratives was also undertaken. In combination with
      high work control, high superior support was associated with an engaged
      participant profile. Job demand was the third important variable with low and
      very high levels associated with participation. With regard to high likelihood of
      future participation, among respondents with age older than 50, high
      predictability of occupational activities and control were identified as a
      significant factor, and among others, high superior support and control. The
      analysis of narratives revealed peer relations and flexible working hours to be
      positively linked to participation and general job stress was identified as
      having a bidirectional relationship. Employees stated that stress led them to
      take advantage of these programs as a source of relief and that their
      availability/participation has contributed to lowering their stress. These
      findings inform practitioners about the importance of addressing poor
      psychosocial factors as a participation barrier and having a holistic approach to
      employee well-being.

PMID- 29599664
TI  - Evaluating ESA CCI soil moisture in East Africa.
AB  - To assess growing season conditions where ground based observations are limited
      or unavailable, food security and agricultural drought monitoring analysts rely
      on publicly available remotely sensed rainfall and vegetation greenness. There
      are also remotely sensed soil moisture observations from missions like the
      European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) and NASA's
      Soil Moisture Active Passive (SMAP), however these time series are still too
      short to conduct studies that demonstrate the utility of these data for
      operational applications, or to provide historical context for extreme wet or dry
      events. To promote the use of remotely sensed soil moisture in agricultural
      drought and food security monitoring, we use East Africa as a case study to
      evaluate the quality of a 30+ year time series of merged active-passive microwave
      soil moisture from the ESA Climate Change Initiative (CCI-SM). Compared to the
      Normalized Difference Vegetation index (NDVI) and modeled soil moisture products,
      we found substantial spatial and temporal gaps in the early part of the CCI-SM
      record, with adequate data coverage beginning in 1992. From this point forward,
      growing season CCI-SM anomalies were well correlated (R>0.5) with modeled,
      seasonal soil moisture, and in some regions, NDVI. We use correlation analysis
      and qualitative comparisons at seasonal time scales to show that remotely sensed
      soil moisture can add information to a convergence of evidence framework that
      traditionally relies on rainfall and NDVI in moderately vegetated regions.

PMID- 29599665
TI  - Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in 2017.

PMID- 29599666
TI  - Structure and function of the epidermal barrier in patients with atopic
      dermatitis - treatment options. Part one.
AB  - Atopic dermatitis is a chronic, recurrent inflammatory skin disease, which is
      frequently familial. The main cause of the disease seems to be a defect of the
      epidermal barrier resulting from a genetic predisposition concerning the
      epidermis, functioning of the immune system as well as environmental factors
      (which are not related to the immune system). Genes responsible for encoding
      protein S100, filaggrin, proteases and their inhibitors are the main genes
      related to the problem of epidermal barrier dysfunction. There is a close
      connection between structural and immunological processes. Increased expression
      of cytokine Th2 profile belongs to the latter category. The objective of the
      present paper is to describe the influence of aforementioned factors on epidermis
      structure and dysfunction which leads to clinical symptoms of atopic dermatitis.

PMID- 29599668
TI  - Selected presentations of lip enlargement: clinical manifestation and
      differentiation.
AB  - Lip enlargement may be an important symptom of either systemic or local diseases.
      On the basis of selected age-matched clinical cases we present the possible
      causes of lip swelling. We describe the most representative symptoms and
      recommend treatment of these pathologies. We differentiate lip swelling in
      Miescher syndrome, monosymptomatic form of Melkersson-Rosenthal syndrome, lip
      swelling in erythema multiforme and Stevens-Johnson syndrome and lip hemangioma
      and mucous extravasation cyst. We compare different causes of lip edema and
      indicate the most helpful diagnostic and treatment methods.

PMID- 29599667
TI  - Langerhans cell histiocytosis in children - a disease with many faces. Recent
      advances in pathogenesis, diagnostic examinations and treatment.
AB  - Langerhans cell histiocytosis is a rare clonal disease characterized by the
      proliferation of CD1a-positive immature dendritic cells. The purpose of this
      article was to present an updated review of recent advances in the pathogenesis,
      clinical features, imaging and treatment of this disease. The discovery of
      oncogenic BRAF mutations and the presence of proinflammatory cytokines and
      chemokines confirmed the unusual characteristics of this disease. Currently,
      children with organ involvement who do not have a good response to chemotherapy
      and have neurodegeneration or diabetes insipidus are the most problematic
      patients. Further research is needed to improve the results of treatment.

PMID- 29599669
TI  - X-linked TLR7 gene polymorphisms are associated with diverse immunological
      conditions but not with discoid lupus erythematosus in Polish patients.
AB  - Introduction: Toll-like receptor 7 (TLR7) is an important molecule involved in
      the development of autoimmunity and the response to different pathogens. Several
      polymorphisms within the TLR7 gene were previously found to be associated with
      systemic lupus erythematosus (SLE). However, none of those studies investigated
      the TLR7 promoter flanking variants rs1634318 and rs1616583. TLR7 gene diversity
      has not been analyzed with respect to discoid lupus erythematosus (DLE)
      development, while its role in the human immunological response to fungal
      infection is not fully known. Aim: To clarify the potential involvement of two
      novel single-nucleotide polymorphisms (SNPs) located in the TLR7 gene (rs1634318
      and rs1616583) in a variety of immune-related conditions, we studied the
      variability of these loci in patients from a Polish population with SLE and DLE,
      as well as in immunocompromised patients who were affected by invasive
      aspergillosis (IA) and those who were not affected. Material and methods: Real
      time polymerase chain reaction was used to genotype SNPs. Statistically
      significant differences between case and control groups for both allele and
      genotype frequencies were assessed using the chi2 test with Yates' correction or
      two-tailed Fisher's exact test. The results were Bonferroni-corrected for
      multiple comparisons and odds ratios were calculated. Results: Two polymorphisms
      located in TLR7 might be associated with the development of SLE but not DLE
      within the Polish population. Moreover, variation of the two investigated SNPs
      was found to be associated with IA in immunocompromised Polish patients.
      Conclusions: In Polish patients, TLR7 promoter flanking gene polymorphisms might
      be associated with IA and SLE but not DLE.

PMID- 29599670
TI  - Dermoscopic assessment of skin toxicities in patients with melanoma during
      treatment with vemurafenib.
AB  - Introduction: The use of vemurafenib in melanoma has improved the survival of
      patients; however, it is associated with skin toxicities. Aim: To assess skin
      toxicities by dermoscopy in patients treated with vemurafenib. Material and
      methods: Eight patients with BRAF V600 mutation positive metastatic melanoma were
      examined dermoscopically during vemurafenib treatment. All skin lesions occurring
      during therapy were assessed clinically and dermoscopically using a hand-held
      dermoscope with polarised and non-polarised light. Skin lesions suspected for
      malignancy appearing during therapy were totally surgically excised with
      consecutive histopathological examination. Results: All 8 examined patients
      developed skin toxicity. The majority of patients (7/8) presented G1 skin
      toxicity according to CTCAE version 4.3. Only 1 of them had G2 skin toxicity. The
      most common dermoscopy findings in our study were hyperkeratotic verrucas in 5
      patients (5/8) with structureless pattern. In some of them we also observed
      central dots, exophytic proliferation, hairpin vessels and homogeneous
      haemorrhage. Other findings were hyperkeratosis of the nipples (5/8) with
      brownish to yellowish, angular clods with a tendency to be more confluent in
      dermoscopy. Palmar plantar erythrodysaesthesia (3/8) showed dermoscopically a
      yellowish, homogeneous pattern. Four melanocytic skin lesions in 2 patients were
      surgically excised due to suspected malignant transformation. In most of them we
      observed an atypical pigmented network (abrupt cut-off, big holes), atypical
      globules and a homogeneous blue pattern; however, histopathological diagnosis
      excluded any malignancy. Conclusions: Dermoscopy seems to be an easily performed
      and valuable method for assessment of skin toxicities during oncological therapy,
      at any time of the treatment.

PMID- 29599671
TI  - Trends in basal cell carcinoma incidence rates: a 16-year retrospective study of
      a population in central Poland.
AB  - Introduction: Basal cell carcinoma (BCC) is the most commonly occurring cancer
      worldwide, and the overall incidence is still rising. Unfortunately, the cancer
      registry in Poland does not record BCC individually. Thus, the incidence of BCC
      in a defined population is unknown. Aim: Analysis of incidence rates of primary
      BCC in central Poland during 16 years considering sex, site distribution and age
      to determine trends. Material and methods: We retrospectively included all cases
      of BCC which were diagnosed and treated in the Department of Dermatology and
      Venereology, Medical University of Lodz, during the 16-year period from 1999 to
      2015. Results: We recorded 945 BCCs occurring in 890 patients (504 females - 57%,
      386 males - 43%). Patient's age was between 21 and 94. A distinct increase in BCC
      was observed after 1999, while after 2010 during the next 2-year period a slight
      decrease was noted. A statistically significant correlation was observed between
      histopathological types of BCC and the location of the lesions. The superficial
      type predominates on photoprotected areas, especially on the trunk, while the
      nodular type occurs mainly in facial areas. No statistically significant
      correlation was observed between histopathological types of BCC and sex. We found
      a significant increase in incidence for superficial BCC among middle-age
      patients, while the nodular type was observed more frequently among elderly
      subjects. Conclusions: Basal cell carcinoma is quite common in Poland and
      predominantly develops in the facial area. In middle-age patients the most common
      is superficial BCC, while in elderly people the nodular type is most common.
      Based on our results we assume that there is a strong need to educate general
      physicians to enable them to diagnose BCC in the early stages.

PMID- 29599672
TI  - The effect of subcutaneous methotrexate on markers of metabolic syndrome in
      psoriatic patients - preliminary report.
AB  - Introduction: Methotrexate (MTX) has anti-proliferative and anti-inflammatory
      effects in psoriasis. Moreover, low doses can reduce the risk of developing
      cardiovascular diseases. It turns out that psoriasis and atherosclerosis have a
      similar pathogenetic mechanism: the same pro-inflammatory cytokines, Th1 and
      Th17, are involved in both diseases. Aim: To evaluate the effects of metabolic
      markers, protective cytokines (interleukin 10 (IL-10), transforming growth factor
      beta (TGF-beta)) and a marker of endothelial damage (endocan) in patients with
      plaque psoriasis. Material and methods: The study included 24 patients aged 27-69
      years (9 female, 15 male) with plaque psoriasis. The metabolic syndrome according
      to the International Diabetes Federation (IDF) was evaluated. The laboratory
      tests were performed under fasting conditions: C-reactive protein (CRP), glucose,
      total cholesterol, triglycerides, high-density lipoprotein (HDL), uric acid,
      endocan, IL-10, and TGF-beta. After 12 weeks of treatment with MTX injections 15
      mg/week, every patient was assessed with the same laboratory tests. Results:
      After treatment we observed a statistically significant increase of endocan and
      IL-10, but no significant differences in the titer of TGF-beta. C-reactive
      protein was reduced by approximately 54.7%. No improvement of lipid profile was
      observed, and even a significant increase in triglycerides was noted. Similarly,
      no significant difference was seen in the case of glucose and uric acid prior to
      and after treatment. Conclusions: Methotrexate in low doses in short-term
      treatment decreases CRP (anti-inflammatory effect) and increases endocan and IL
      10 (potential protective role). Methotrexate is characterized by good efficacy
      and tolerability in therapy of patients with psoriasis.

PMID- 29599673
TI  - Associations between site of skin lesions and depression, social anxiety, body
      related emotions and feelings of stigmatization in psoriasis patients.
AB  - Introduction: Research has demonstrated a link between psoriasis and a multitude
      of psychological impairments; however, relatively few studies have examined the
      importance of site of skin lesions for negative psychological outcomes in
      psoriasis patients. Aim: To investigate relationships between anatomical location
      of psoriatic lesions and experiences of stigmatization, negative emotional
      attitude towards the body, depression and social anxiety. Material and methods:
      Adult psoriasis patients (N = 193) completed the Stigmatization Scale, the Body
      Emotions Scale, the Beck Depression Inventory and the Social Anxiety
      Questionnaire. The body surface area index was used to assess the location and
      extent of psoriasis. Results: Feelings of stigmatization were found to be most
      closely related to the presence of psoriatic lesions on the chest, and the arms
      and hands. Higher levels of social anxiety were found to be most closely related
      to the location of psoriatic lesions on the head and neck. Negative emotional
      attitude towards the body was found to be most closely related to the location of
      psoriatic lesions on the arms and hands, and on the head and neck. Higher levels
      of depressive symptoms were most closely related to the presence of psoriatic
      lesions on the head and neck, the arms and hands, and the genital area.
      Conclusions: The presence of psoriatic lesions on the head, neck, and chest, and
      also on the arms and hands and the genital area, should alert clinicians to a
      higher risk of psychological impairments. This may help to better recognize and
      prevent cumulative life course impairment.

PMID- 29599674
TI  - Epidemiology of urticaria in Poland - nationally representative survey results.
AB  - Introduction: The prevalence of urticaria is 15-20%. Women are twice as likely to
      be affected. Aim: To present the epidemiology of urticaria and angioedema in
      Poland. Material and methods: A questionnaire-based survey was conducted on a
      representative group of 4,897 individuals, aged 15-74 years. Results: A total of
      11.2% of respondents reported at least one episode of urticaria symptoms in their
      life, and the frequency was higher in females (OR = 1.46; p < 0.001). Single
      episodes accounted for 34.8%, while repeated episodes accounted for 65.2%. Acute
      urticaria was observed in 10.6% (more frequent in females; OR = 1.41; p < 0.001),
      chronic in 0.6%. Median age of the first episode was 15 years. Angioedema was
      observed in 3.2%. The last episode of urticaria symptoms and/or angioedema
      occurred within the previous week in 0.7% of subjects, the last month in 1%, and
      the last year in 2.2%. 8.8% had experienced urticaria symptoms or angioedema over
      1 year prior to the survey. The impact of urticaria symptoms on patients' daily
      activities was rated with 3.8 points on a scale of 0-10. In addition, chronic
      urticaria was rated 6.5, and acute urticaria 3.6. Angioedema and urticaria had a
      negative impact of 5.7 points. Conclusions: Urticaria and angioedema are serious
      health problems in Poland, although their prevalence is below the mean rate for
      the global population. Females are more likely to suffer from these diseases.
      People affected by urticaria most frequently report contact with plants and
      substances, insect bites/stings, and food as the provoking factors.

PMID- 29599675
TI  - Activity of antimicrobial peptides and conventional antibiotics against
      superantigen positive Staphylococcus aureus isolated from patients with atopic
      dermatitis.
AB  - Introduction: Staphylococcus aureus causes a diverse array of diseases, ranging
      from relatively harmless localized skin infections to life-threatening systemic
      conditions. It secretes toxins directly associated with particular disease
      symptoms. Aim: To determine the prevalence of methicillin-resistant S. aureus
      (MRSA) and methicillin-susceptible S. aureus (MSSA) colonization among patients
      with atopic dermatitis and to assess the antimicrobial susceptibility to
      conventional antibiotics and selected antimicrobial peptides among toxin
      producing strains and nonproducing strains. Material and methods: One hundred
      patients with atopic dermatitis and 50 healthy people were microbiologically
      assessed for the carriage of S. aureus. Antimicrobial susceptibility tests were
      performed using the broth microdilution method for conventional antibiotics and
      antimicrobial peptides (CAMEL, Citropin 1.1, LL-37, Temporin A). Detection of
      genes lukS/lukF-PV, tst, sea-sed, eta and etb by multiplex PCR was performed.
      Results: Staphylococcus aureus strains were isolated from the majority of
      patients, from either the skin (75%) or the anterior nares (73%). Among the
      conventional antibiotics tested, the highest rates of resistance were observed
      for ampicillin, daptomycin, lincomycin and erythromycin. Antimicrobial peptides
      did not show significant diversity in activity. Among MSSA strains greater
      differentiation of secreted toxins was observed (sec, eta, pvl, tsst, etb, seb),
      while in the group of MRSA strains secretion of 3 toxins (pvl, eta, seb) was
      noted. Conclusions: Antimicrobial resistance continues to evolve. It is important
      to monitor S. aureus infections. The profile of toxins produced by S. aureus
      strains is an important consideration in the selection of an antimicrobial agent
      to treat infections.

PMID- 29599676
TI  - Cross-sensitization to Artemisia and Ambrosia pollen allergens in an area located
      outside of the current distribution range of Ambrosia.
AB  - Introduction: The role of long-distance transported (LDT) Ambrosia pollen in
      inducing new sensitization and affecting sensitization rates in Artemisia
      sensitized patients is unclear. Aim: The aim of this study was to estimate the
      degree of cross-sensitization to Ambrosia/Artemisia allergens in citizens of
      Poznan (Western Poland). This area is covered by extensive Artemisia populations
      but does not currently have local Ambrosia populations. Material and methods:
      Sera of 119 patients were tested by fluoroenzyme immunoassay (CAP-FEIA system)
      against pollen allergen extracts of Artemisia vulgaris and Ambrosia
      artemisiifolia, an allergenic component of A. vulgaris (nArt v 1), and an
      allergenic component of A. artemisiifolia (nAmb a 1). Skin prick tests (SPTs, n =
      86) were performed with pollen allergen extracts of A. vulgaris and A.
      artemisiifolia. Artemisia and Ambrosia pollen in ambient air was collected (1996
      2013) by a Hirst type volumetric trap sited at roof level (33 m). Results: The
      SPT showed that the prevalence of sensitization to Ambrosia and Artemisia pollen
      exceeded 3.5%, and 10.5%, respectively. The measurements of IgE in blood serum
      (CAP-FEIA) revealed that among Ambrosia-sensitized patients 90.1% (20/22
      patients) were concomitantly sensitized to Artemisia. 59.1% (13/22) of these
      patients reacted to nArt v 1, suggesting primary sensitization to Artemisia
      pollen. Only 2 (9.1%) patients were mono-sensitized to Ambrosia pollen extract,
      but surprisingly not to nAmb a 1. Conclusions: The LDT Ambrosia pollen had a
      negligible effect on the rate of sensitization to Ambrosia allergens in Poznan
      and did not increase the prevalence of sensitization to Artemisia pollen in this
      region. However, the majority of patients showing hypersensitization to Artemisia
      pollen might also present symptoms during elevated episodes of LDT of Ambrosia
      pollen.

PMID- 29599677
TI  - Venom immunotherapy and pregnancy.
AB  - Introductions: The efficiency of venom immunotherapy (VIT) has been well
      documented by many studies. However, the most important for VIT is safety,
      particularly for a pregnant woman and a fetus. Aim: To establish the influence of
      continuation of VIT on pregnant women and offspring. Material and methods: The 6
      women became pregnant during a specific immunotherapy. We retrospectively
      analyzed the influence of the immunotherapy on any complications for the pregnant
      women and their infants. Results: Of the 6 patients who participated in this
      study, four had hyperemesis gravidarum, nausea, and heartburn, and two of them
      had gestational diabetes mellitus symptoms, typical of pregnancy. The observation
      indicated that VIT was safe for the pregnant women and their offspring.
      Conclusions: The VIT is an appropriate therapeutic method for most patients with
      severe anaphylactic reactions after a hymenoptera sting. The observation
      indicated that VIT is safe for pregnant women and for their infants.

PMID- 29599678
TI  - The usefulness of the basophil activation test in monitoring specific
      immunotherapy with house dust mite allergens.
AB  - Introduction: In clinical practice, reliable tools for monitoring specific
      immunotherapy (SIT) are of utmost importance. Aim: To assess the usefulness of
      the basophil activation test (BAT) in monitoring SIT in paediatric patients with
      allergy to house dust mites (HDM). Material and methods: Thirty-one children
      qualified for SIT with HDM, of whom 21 completed the SIT during the observation
      period. The BAT was carried out prior to commencing the SIT (time point BAT1) and
      upon finishing the initial pack of allergy vaccine (cumulative dose of allergen
      12487.5 PNU; BAT2), as well as after the second vaccine pack (cumulative dose of
      allergen 23750.0 PNU; BAT3). Peripheral blood of the patients was stimulated with
      allergen solutions in five concentrations from 0.00225 ng/ml to 22.5 ng/ml.
      Basophil activation was measured by CD63 expression in flow cytometry. Results:
      For the allergen concentration of 0.225 ng/ml, a statistically significant
      decrease in median basophil activation was observed, from 51.29% at BAT1 to 8.48%
      at BAT2 (p = 0.004) and 4.21% at BAT3 (p < 0.001). For the allergen concentration
      of 0.0225 ng/ml, a statistically significant decrease was seen between BAT1
      (1.72%) and BAT3 (0.21%, p = 0.01). Median CD-sens index decreased significantly
      from 1099.02 at BAT1 to 179.31 at BAT2 (p < 0.002) and 168.04 at BAT3 (p <
      0.001). Conclusions: There is a significant decrease in BAT results in the course
      of specific immunotherapy with HDM allergens in children, with the optimum
      allergen concentration for monitoring basophil response at 0.225 ng/ml. The CD
      sens index seems to be a better monitoring parameter than the plain percentage of
      CD63-expressing basophils.

PMID- 29599679
TI  - Seasonal variation of asthma control, lung function tests and allergic
      inflammation in relation to vitamin D levels: a prospective annual study.
AB  - Introduction: There are scarce data about the role of vitamin D (vitD) in asthma
      control related to seasons and other confounders. Aim: To investigate the
      seasonal relationship between vitD levels and asthma control, lung function tests
      (LFTs) and cytokines during a 1-year period, among 7-17-year-old asthmatic
      children. Material and methods: Thirty patients with asthma with house dust mite
      monosensitization were evaluated 3 monthly about the previous month's health and
      vitD related lifestyle factors and asthma control test (ACT), spirometry and
      bronchial provocation test for a year. Serum vitD, vitD binding protein (VDBP),
      total IgE levels, absolute eosinophil and Treg counts and cytokine levels were
      simultaneously measured. The seasonal changes of vitD and other parameters and
      the relationship between 120 pooled data sets of vitD and major outcomes were
      evaluated. Results: Mean vitD levels, forced expiratory volume in 1 s (FEV1%) and
      ACT score were lowest in winter and highest in summer. Pooled vitD levels were
      positively correlated with pooled ACT scores, Treg counts, FEV1% values and VDBP
      levels and negatively with total immunoglobulin E (IgE) and interleukin-4 (IL-4)
      levels and bronchodilator response. VitD levels were positively associated with
      ACT score, and FEV1% value and negatively with serum IgE level and bronchodilator
      response after adjusting for confounders. Conclusions: This study revealed that
      asthma control measures, LFTs and IgE levels were significantly related to serum
      vitD levels, independent from age, body mass index, inhaled corticosteroid use,
      sun exposure and season among asthmatic children. Vitamin D levels showed a
      positive correlation with Treg counts and a negative correlation with Th2 type
      cytokines.

PMID- 29599680
TI  - The first case of drug-induced pseudoscleroderma and eczema craquele related to
      nab-paclitaxel pancreatic adenocarcinoma treatment.

PMID- 29599681
TI  - A case of granuloma faciale successfully treated with oral prednisone, tranilast
      and thalidomide.

PMID- 29599682
TI  - Paraneoplastic pemphigus with anti-desmocollin 3 autoantibodies and chronic
      lymphocytic leukemia.

PMID- 29599683
TI  - Pityriasis rosea in a patient with retrovirus infection: a reply.

PMID- 29599684
TI  - Occupational exposure as a presumable cause of subcutaneous sarcoidosis in a
      tannery worker - case report and review of the literature.

PMID- 29599685
TI  - Household decision-making around food in rural Tajikistan: a cross-sectional
      study to help extension workers in the field.
AB  - This study was conducted to research and develop recommendations for gender
      transformative approaches that will address misconceptions around food and
      nutrition, and reducing barriers around dietary diversity within rural Khatlon
      Province, Tajikistan. Most of the population in Tajikistan live in rural areas
      and spend a large part of their income on food. While stunting in children under
      5 years has decreased, acute malnutrition and the number of underweight children
      has increased. This is a qualitative, cross-sectional study that involved
      secondary data analysis, key informant interviews (KIIs), and focus group
      discussions (FGDs) to gauge appropriate interventions for agricultural extension
      agents seeking to improve the nutritional outcomes of their communities. In
      February of 2017, data were collected from 4 KIIs and 15 FGDs that were
      stratified as mothers with young children, mothers-in-law, and husbands, across
      12 different villages. Analysis of the KIIs and FGDs included NVivo software for
      coding and to uncover the most salient themes and characteristics from each. The
      participants of this study reported several misconceptions and taboos surrounding
      certain foods, especially during pregnancy, and food practices for children under
      the age of 5 years. Results also indicated a household hierarchy of decision
      making surrounding food that included who buys, cooks, and decides what to buy.
      The findings of this study will be used as a springboard to launch gender
      responsive and nutrition-sensitive interventions through the local agricultural
      extension agents.

PMID- 29599686
TI  - Alignments of endocrine, anthropometric, and metabolic parameters in type 2
      diabetes after intervention with an Okinawa-based Nordic diet.
AB  - Background: An Okinawa-based Nordic diet with moderately low carbohydrate content
      and high fat and protein content has been shown to improve anthropometry and
      metabolism in type 2 diabetes. Objective: The objectives of this study were to
      measure plasma or serum levels of hormones regulating energy metabolism and
      metabolic control, that is, cholecystokinin (CCK), Cortisol, C-peptide, ghrelin,
      glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic
      polypeptide (GIP), insulin, leptin, plasminogen activator inhibitor-1 (PAI-1),
      polypeptide YY (PYY), resistin, and visfatin after this diet intervention, and to
      determine partial correlations between hormonal levels and anthropometric and
      metabolic responses. Design: A total of 30 patients (17 women) with type 2
      diabetes, mean age 57.5 +/- 8.2 years, and body mass index (BMI) 29.9 +/- 4.1
      kg/m2 were served the diet for 12 weeks. Fasting hormones were measured by
      Luminex and enzyme-linked immunosorbent assay (ELISA) before study start and
      after 12 and 28 weeks, along with anthropometric and metabolic parameters.
      Result: The levels of CCK (P = 0.005), cortisol (P = 0.015), C-peptide (P =
      0.022), glucagon (P = 0.003), GLP-1 (P = 0.013), GIP (P < 0.001), insulin (P =
      0.004), leptin (P < 0.001), and PYY (P < 0.001) were lowered after dietary
      intervention. These reduced levels only remained for PYY at week 28 (P = 0.002),
      when also ghrelin (P = 0.012) and visfatin (P = 0.021) levels were reduced.
      Changes of glucose values correlated with changed levels of C-peptide and PYY (P
      < 0.001), insulin (P = 0.002), and PAI-1 (P = 0.009); changes of triglyceride
      values with changed levels of C-peptide, insulin, and PYY (P < 0.001) and PAI-1
      (P = 0.005); changes of insulin resistance with changes of leptin levels (P =
      0.003); and changes of BMI values with changed levels of C-peptide, insulin, and
      leptin (P < 0.001). Conclusions: Okinawa-based Nordic diet in type 2 diabetes has
      significant impact on the endocrine profile, which correlates with anthropometric
      and metabolic improvements.

PMID- 29599687
TI  - Knowledge, attitudes, and practices of health-care workers regarding hand hygiene
      guidelines in Al-Qassim, Saudi Arabia: A multicenter study.
AB  - Introduction: Hand hygiene is one of the most important ways to reduce the
      prevalence of nosocomial infections, morbidity, mortality, and health-care costs
      among hospitalized patients worldwide. Objectives: We addressed this study to
      assess knowledge, attitudes, and practices regarding hand hygiene guidelines
      among health-care workers. Methods: A multicenter cross-sectional study conducted
      from October to December 2015 including three hospitals in Al-Qassim, Saudi
      Arabia. A total of 354 participants completed a self-administered survey on
      knowledge, attitudes, and practices of hand hygiene. Analysis of variance was
      used to compare knowledge level across age, gender, profession, and hospitals.
      All analyses were performed with SPSS, version 21. Results: Overall, the average
      knowledge score was 63%. There were significant differences in knowledge level
      across groups. Health-care workers over the age of 30 had higher scores than
      those younger than 30. Health-care workers at the tertiary hospital had higher
      scores than those at the secondary hospitals. Nearly, all reported positive
      attitudes toward hand hygiene as well as adhering to the guidelines regularly.
      Further, they reported that soap and water were the most common agents for
      cleaning hands. Conclusion: The study findings indicate that there are gaps in
      the knowledge, which could be addressed with brief and more frequent training
      sessions, particularly in the secondary hospitals. However, the hand hygiene
      guidelines are well-known by the staff and well promoted in the hospitals
      reflected by the positive attitudes. Further improvements in adherence to the
      hand hygiene guidelines will continue to decrease the likelihood of nosocomial
      infections.

PMID- 29599688
TI  - Knowledge, attitude, and practice toward evidence-based medicine among hospital
      physicians in Qassim Region, Saudi Arabia.
AB  - Objectives: To determine the knowledge, attitude, and practice regarding evidence
      based medicine (EBM) among hospital physicians in Qassim region of Saudi Arabia.
      Methods: It is a cross-sectional study. A self-administered questionnaire survey
      was done among 288 physicians working in secondary and tertiary care centers. The
      study was conducted between June and September 2015. Results: The overall
      response rate for the survey was 72%. Majority of the respondents had a positive
      attitude toward EBM and welcomed the concept. A total of 83% respondents stated
      that they used EBM in their daily practice and 93.5% agreed that practicing EBM
      improves patient care. There was a moderate level of awareness regarding
      extracting information from journals and clinical evidence databases. Although
      the respondents were aware and demonstrated familiarity with the process of
      knowledge extraction procedures to determine the best care, as many as 40% did
      not use them. The respondents had a poor overall understanding of the technical
      terms used in EBM. Among the respondents, 38.5% thought that the best way to move
      from opinion-based medicine to EBM was through learning the skills of EBM. The
      factors that positively affected physician awareness included: Academic
      qualification and professional title. Knowledge and attitude were affected by
      qualification, professional title and specialty. Conclusion: The attitude of most
      physician practitioners in this study is favorable toward EBM, but this was not
      correlated with knowledge and awareness. The inclusion of physician training
      courses in EBM concepts, technical terms and applied practice is highly
      recommended.

PMID- 29599689
TI  - Validity and reliability of the Arabic version of the the EuroQOL (EQ-5D). A
      study from Saudi Arabia.
AB  - Objectives: The EuroQOL five-dimension questionnaire (EQ-5D) is one of the most
      widely used tools to evaluate health-related quality of life (HRQOL). Studies on
      the psychometric features of the EQ-5D in the Gulf region of the Middle East are
      lacking. This study is aimed at evaluating the validity and reliability of the
      Arabic version of the EQ-5D in Saudi Arabia. Methods: The study was done
      utilizing a convenience sample of Arabic-speaking adult patients or visitors at
      the outpatient clinic at King Abdulaziz Medical City (KAMC) in Riyadh during
      October-December 2015. Participants were interviewed using translated into Arabic
      versions of the EQ-5D and the Short Form Health Survey (SF-36). Known-group
      construct validity of the EQ-5D and visual analog scale (EQ-VAS) was assessed
      through testing a number of hypotheses comparing responses to EQ-5D dimensions or
      EQ-VAS to SF-36 scores by dimension and external variables. Test-retest
      reliability was also assessed. Results: Eighty subjects were included in the
      study. Mean +/- standard deviartion age was 33.0 +/- 11.6 years, with 51% of
      females. Responses to EQ-5D dimensions revealed that the proportion of
      respondents reporting problems ranged from 6% for problems with self-care to 48%
      for pain/discomfort. All of the five hypotheses linking EQ-5D responses to
      external variables were satisfied. Test-retest reliability was evaluated using
      Cohen's kappa, which ranged from 0.53 to 1.00. Conclusion: Validity and
      reliability of the Arabic EQ-5D were established for evaluating HRQOL in Saudi
      Arabia. Further studies are warranted to evaluate the validity and reliability of
      this standard tool in other Arabic-speaking countries with varying cultures.

PMID- 29599691
TI  - An in vitro comparison of the fracture resistance of standard and modified mesio
      occluso-distal cavity designs restored with resin composite restoration.
AB  - Objectives: The main goal of this study was to evaluate the fracture resistance
      of maxillary second premolar teeth with standard and conservative mesio-occluso
      distal (MOD) cavity designs. Methods: Sixty maxillary second premolars were
      randomly divided into 6 Groups of 10 teeth. G1 consisted of intact teeth. G2 was
      prepared with separated proximal boxes that were designed to be 1 mm
      approximately above the cement-enamel junction for the cervical margins. The
      occlusal outline of the proximal was performed as approximately half of the
      intercuspal distance buccolingually and one-third of the mesiodistal dimension.
      The proximal preparation was standardized in all tested groups. G3 was prepared
      with an occlusal extension that extended approximately one-third of buccolingual
      width and 2 mm in depth. G4 was prepared with the occlusal extension of 1mm in
      depth and width. G5: The occlusal extension was 1mm in depth and 2 mm in width.
      G6: The occlusal extension was 2 mm in depth and 1 mm in width. Samples were
      restored with composite resin and subjected to load to failure test to evaluate
      the fracture resistance. Results: G1 showed the highest fracture resistance value
      (1737.1 N) while G3 had the lowest mean value (522.9 N). Furthermore, the
      fracture resistance of G4 and G5 was significantly higher than G3 and G6 (P <
      0.05), where in both groups, the preparation of the occlusal extension mostly
      remained in the enamel layer. Conclusion: Modified MOD cavity designs with 1 mm
      depth in the enamel layer have significantly higher fracture resistance than the
      standard MOD cavity.

PMID- 29599690
TI  - The expression of leptin in oral wound healing in diabetes mellitus: An
      experimental study.
AB  - Objective: The present work evaluated histologically and immunohistochemically
      the expression of leptin during healing of the incisional oral mucosal wound in
      diabetic rats as compared to healthy rats. Methods: Twenty-four adult male
      Sprague-Dawley rats weighing on average 150-200 g were allocated equally into two
      groups: Group I (control) and Group II (diabetic). Diabetes was induced by a
      single intraperitoneal injection of streptozotocin dissolved in distilled water.
      Each animal received experimental incision in buccal mucosa and sutured, and the
      specimens were collected from the buccal mucosa of each animal at intervals of 7,
      14, and 21 days and routinely processed for H and E and immunohistochemical
      staining for leptin. All measurement data were calculated as a mean +/- standard
      deviation. Results: Leptin expression was observed in the epithelium and the
      vascular endothelial cells in both groups. In both the control and diabetic
      groups, the expression of leptin was significantly increased with time, and there
      was an extreme highly significant increase in the control group than in diabetic
      group after 7, 14, and 21 days (P = 0.000). Conclusion: The results of the
      present study suggested that leptin may promote wound healing in rat's normal
      oral mucosa more than in diabetic. Further studies are needed to clarify the
      exact molecular mechanisms of leptin's effects on wound healing and to determine
      the usefulness of leptin as a treatment to promote wound healing in the oral
      mucosa in diabetic and non-diabetic patients.

PMID- 29599692
TI  - Barriers to effective feedback in undergraduate medical education: Case study
      from Saudi Arabia.
AB  - Objectives: Students' feedback is an essential source of data for evaluation and
      improvement of the quality of education. Nonetheless, feedback may be routinely
      practised for accreditation purposes, and it is considered as a ritual employed
      by students, which makes its effectiveness questionable. The aim of this study is
      to explore and analyze the students' perceptions about the importance of feedback
      and the barriers for effective feedback and suggest proper ways to overcome these
      barriers. Methods: This cross-sectional, anonymous, questionnaire-based study was
      conducted in the College of Medicine, Qassim University. A total of 299 medical
      students, composed of 185 male and 114 female, from different levels during
      December 2015 participated. Mean value, standard deviation, and proportion were
      used to quantify the quantitative and categorical study and outcome variables.
      Results: 47% of students responded to the questionnaire with more participation
      of juniors and females. Half of the students believed that feedback is not
      important and agreed for the presence of barriers for effective feedback. 5th
      level students exhibited higher resistance for participation in feedback, and
      there was a significant difference between male and female students. Promisingly,
      most of the participant did not believe the presence cultural barrier for
      feedback. Conclusion: Saudi medical students are willing to involve in effective
      feedback. Some barriers that make feedback practised as tokenistic is present.
      They can be overcome through proper orientation and appropriate closing the loop
      with response to the feedback declared to students. Further investigation is
      needed to explore barriers to feedback in higher education settings and help
      designing an approach to enhance the effectiveness of feedback on a national
      level.

PMID- 29599693
TI  - Functional analysis of lower limbs in individuals infected with the human
      immunodeficiency virus.
AB  - Objectives: The objective of this research was to analyze the functional changes
      of lower limbs by means of surface electromyography in patients with acquired
      immunodeficiency syndrome. Methods: A total of 60 men and women (age mean of
      36.77 +/- 9.33 years) were divided into two groups: 30 individuals with human
      immunodeficiency virus group (HIVG) Subtype 1 and 30 healthy individuals control
      group. Muscle activity was evaluated using surface electromyography (sEMG). sEMG
      measurements were made while the subjects assumed the static positions: Rest in
      orthostatism (RS), squat "normalization factor," right and left single leg
      support (RSLS, LSLS) and during functional activities: Right and left single leg
      step rise (RSLSR, LSLSR), right and left single leg step down (RSLSD, LSLSD),
      rising and seating on a chair (RC, SC). Results: To sEMG results revealed
      statistically significant values in the conditions of RSLS to left semitendinosus
      muscle, for LSLS to right and left semitendinosus, right rectus femoris and right
      gluteus medius muscles, for LSLSR to right rectus femoris and right tensor
      fasciae latae muscles, for RSLSD to right and left semitendinosus and right
      rectus femoris muscles, for RC to right rectus femoris and left gluteus medius
      muscles and for SC to right semitendinosus, right rectus femoris and right and
      left gluteus medius muscles. Conclusion: It can be concluded that individuals
      with acquired immunodeficiency syndrome presented changes in lower limb muscle
      activity.

PMID- 29599694
TI  - Utilization of clinical pathway on open appendectomy: A quality improvement
      initiative in a private hospital in the Philippines.
AB  - Objective: This study was done to evaluate the utilization of clinical pathway
      (CP) on open appendectomy as a quality improvement (QI) initiative. Methods: The
      CP document was developed from the clinical practice guideline created by the
      Philippine College of Surgeons using an event-timeline tabular checklist format.
      After a hospital-wide education, the CP was implemented on January 1, 2010, as
      the QI intervention. Appendectomies done 4 years before the intervention were
      assigned to the pre-pathway group while those done 5 years after were assigned to
      the post-pathway group. Demographic data were collected including the different
      clinical outcomes such as the average length of stay (ALOS), comorbidity,
      diagnostic modality used, hospital cost, and variance rate. Data were presented
      as mean +/- standard deviation and percentage which ever were applicable.
      Statistical analysis was done using Student t-test for numerical data and Chi
      square for dichotomous data. Significance was set at P < 0.05. Results: Two
      hundred ninety-five patients were included in the study. Separate analysis was
      done for uncomplicated (Pre-pathway Group, n = 49 and Post-pathway group, n =
      139) and complicated (pre-pathway Group, n = 38 and Post-pathway Group, n = 69)
      open appendectomies. Results showed that diagnosis was achieved through history
      and physical examination. Ultrasound use did not significantly differ between
      groups and types of open appendectomy. Major findings showed a significant
      decrease in ALOS, hospitalization cost, and variance in the post-pathway group
      compared with the pre-pathway group (P < 0.05). Conclusion: These findings
      supported the use of CP in QI of health care in commonly done surgeries like
      appendectomy.

PMID- 29599695
TI  - Persistent anxiety and in-hospital complications after acute coronary syndrome.
AB  - Objectives: To investigate the effects of pre-event persistent anxiety on in
      hospital complications and length of stay (LOS) in patients who experienced acute
      coronary syndrome (ACS). Methods: This was a prospective study with patients
      seeking treatment for ACS events. Anxiety was measured 2 times before the event
      in 600 patients with pre-existing coronary heart disease (CHD). Patients were
      followed for 2 years or until they developed an ACS event. 120 patients developed
      ACS events (rate 20%). Complications and LOS were abstracted from medical
      records. Results: Persistently non-anxious patients have lower anxiety scores at
      3 months follow-up than baseline (mean [standard deviation (SD)], 6.1 [0.24] vs.
      3.9 [0.95], P <0.01). Patients with persistent anxiety had significantly higher
      complication rates than non-anxious patients (mean [SD], 0.71 [0.12] vs. 0.15
      [0.11], P <0.05). In a multiple logistic regression, persistent anxiety was an
      independent predictor of complications. Patients who were persistently anxious
      were at 5 times higher risk for developing complications (odds ratio = 5.0, 95%
      confidence interval: 1.27-38.8, P < 0.05). Conclusion: Anxiety measured up to 2
      years before an ACS event was predictive of in-hospital complications. Clinicians
      caring for patients with CHD need to be as equally aware of the importance of
      assessing and treating persistent anxiety as clinicians caring for patients
      hospitalized for an ACS.

PMID- 29599696
TI  - Merits of trabeculectomy in advanced and end-stage glaucoma.
AB  - Objectives: The aim of the study was to evaluate intraocular pressure (IOP)
      control, potential benefits, and associated complications in advanced cases of
      glaucoma (visual acuity of <6/60) after trabeculectomy. Although many studies of
      trabeculectomy in glaucoma patients have been done, very few in such advanced
      cases. Methods: The study was done on 60 cases of advanced primary open-angle
      glaucoma (POAG). Trabeculectomy was done and IOP control was assessed. Pre
      operative workup included a detailed history, slit lamp biomicroscopy, Goldmann
      applanation tonometry, gonioscopy using Goldmann 2 mirror lens, and detailed
      fundus examination with the 78D lens. All the patients were to undergo optical
      coherence tomography and Humphrey automated perimetry. Results: Out of 60
      patients with POAG, 48 were males and 12 were females with a ratio of 4:1. Of all
      the 60 cases, 36 had a visual acuity of 20/200, 16 had a visual acuity of hand
      movements, and eight patients had a visual acuity of perception of light. The
      mean pre-operative IOP was measured as 37.01 mmHg with standard deviation (SD)+/-
      8.82. The mean post-operative IOP was found 17.92 mmHg with SD +/- 3.17. There
      was a mean drop of 19 mmHg of IOP postoperatively. P value was highly significant
      (P < 0.000). Conclusion: Trabeculectomy is a successful method of controlling IOP
      in patients with advanced glaucoma. Trabeculectomy is the method of reducing IOP
      in medically uncontrolled patients. A pain-free eye was associated with better
      quality of life in patients. A successful trabeculectomy helps to preserve the
      residual vision in such patients.

PMID- 29599697
TI  - Links between the Prophet Muhammad (PBUH) recommended foods and disease
      management: A review in the light of modern superfoods.
AB  - Nutrition and other bioactive natural products present in specific foods within a
      balanced diet play an indispensable role in maintaining and promoting human
      health. Plants are rich sources of a balanced nutrition because of high content
      of bioactive products; hence, most of them recently have acquired the status of
      superfoods. It has been used since ancient times for the treatment of various
      ailments, and these traditional medicines still remain as one of the most
      affordable and easily accessible sources of treatment in the primary health-care
      system. The scientifically based use of these superfoods date back to the era of
      Prophet Muhammad along with other historical uses of plant products. Prescription
      of a large number of herbal foods such as dates, pomegranate, olives, figs,
      grapes, and black seeds was successfully proposed by him. These recently have
      become superfoods with their powerful healing properties and act as favorable
      dietary interventions for disease prevention as well as for the good maintenance
      of health. The use of these foods as ingredients of natural origin with fewer
      side effects seems to be more favorable than the chemical treatment, which is
      often complicated. The present review is an attempt to provide a brief survey of
      the literature on scientifically based significance of these superfoods carried
      out by various researchers and exploration of a wide spectrum of their
      pharmacological actions which include antidiabetic, anticancer, immune modulator,
      analgesic, anti-inflammatory, and hepatoprotective properties.

PMID- 29599699
TI  - A literature review of empirical research on learning analytics in medical
      education.
AB  - The number of publications in the field of medical education is still markedly
      low, despite recognition of the value of the discipline in the medical education
      literature, and exponential growth of publications in other fields. This
      necessitates raising awareness of the research methods and potential benefits of
      learning analytics (LA). The aim of this paper was to offer a methodological
      systemic review of empirical LA research in the field of medical education and a
      general overview of the common methods used in the field in general. Search was
      done in Medline database using the term "LA." Inclusion criteria included
      empirical original research articles investigating LA using qualitative,
      quantitative, or mixed methodologies. Articles were also required to be written
      in English, published in a scholarly peer-reviewed journal and have a dedicated
      section for methods and results. A Medline search resulted in only six articles
      fulfilling the inclusion criteria for this review. Most of the studies collected
      data about learners from learning management systems or online learning
      resources. Analysis used mostly quantitative methods including descriptive
      statistics, correlation tests, and regression models in two studies. Patterns of
      online behavior and usage of the digital resources as well as predicting
      achievement was the outcome most studies investigated. Research about LA in the
      field of medical education is still in infancy, with more questions than answers.
      The early studies are encouraging and showed that patterns of online learning can
      be easily revealed as well as predicting students' performance.

PMID- 29599698
TI  - The effectiveness of alitretinoin for the treatment of chronic hand eczema: A
      meta-analysis.
AB  - Alitretinoin is a new oral retinoid authorized for use in grownups that have
      severe chronic hand eczema (CHE). A comprehensive search to solicit all studies
      of alitretinoin for the treatment of CHE. A comprehensive search to solicit all
      studies of alitretinoin for the treatment of CHE including randomized controlled
      trials (RCTs) or uncontrolled trials, re-treatment studies, open-label studies,
      or observational studies, along with case series of 10 or more participants.
      Physician global assessment (PGA), patient global assessment (PaGA) and modified
      total lesion symptom score (mTLSS) are the methods and outcomes criteria.
      Generated effect size and 95% confidence intervals were calculated for the
      outcomes. Heterogeneity and publication bias were also tested for all selected
      trials. When a noteworthy Q statistic (P < 0.1) demonstrates the heterogeneity
      crosswise over studies, an arbitrary impact model is used. On the other hand, a
      settled effect model is when heterogeneity is not shown. The initial search
      yielded 408 records of which 15 articles were selected. The 15 clinical trials
      included 3734 patients with CHE. Among alitretinoin-treated patients, the PGA
      effect size was directly proportional to the drug dosage, ranging from 40% to
      69%, while the PaGA score ranged from 28.8% to 62.4%, and mTLSS ranged from 60.4%
      to 76.9%, much higher than placebo. A higher drug dose was about twice as
      effective as lower dose. The odds ratio for a better outcome with drug treatment
      taking duration into account was about 3-4 times that versus placebo. In
      conclusions, alitretinoin cleared lesions in about 50% of cases, particularly
      using a higher dose for a longer duration.

PMID- 29599700
TI  - Effect of testosterone boosters on body functions: Case report.
AB  - Testosterone boosters are supplementary substances that can be used for the
      purpose of increasing testosterone levels in the blood. This study aimed to
      evaluate the side effects and health risks of testosterone boosters among
      athletes. A sportsman came to the King Saud Hospital, Unaizah, Qassim, Saudi
      Arabia, suffering from abdominal pain. The attending doctor requested general
      laboratory tests. He admitted to having consumed two courses of a testosterone
      booster over a period of 42 days following the instructions of the manufacturer.
      In total, the athlete in question consumed several courses, twice before the
      abdominal pain started and twice after it subsided. The blood tests and reports
      suggested that the commercial product consumed might negatively affect several
      hepatic functions and resulted in slightly increased testosterone concentrations
      after the fourth course. In conclusion, administration of testosterone booster
      products, although obtained from trusted sources, may still present some health
      risks. Further studies with large sample size and for a long period need to be
      done to confirm the current findings.

PMID- 29599701
TI  - Rare case of a mandibular first molar with seven canals confirmed by cone beam
      computed tomography and its endodontic management.
AB  - The endodontic treatment of a mandibular molar with aberrant canal configuration
      can be diagnostically and clinically challenging. This case report presents the
      treatment of a mandibular first molar with seven root canals, of which four
      canals were located in the mesial root and three in distal root. This case
      presents a rare anatomic configuration and points to the importance of expecting
      and searching for additional canals.

PMID- 29599702
TI  - Age-Related Changes in Neuromodulatory Control of Bladder Micturition
      Contractions Originating in the Skin.
AB  - The brainstem is essential for producing micturition contractions of the urinary
      bladder. Afferent input from perineal skin evoked by gentle mechanical
      stimulation inhibits micturition contractions by decreasing both ascending and
      descending transmissions between the brainstem and spinal cord. Dysfunction of
      this inhibitory mechanism may be one cause of the increase in the prevalence of
      overactive bladder in old age. The aim of this study was to examine effect of
      aging on function of skin afferent fibers that inhibit bladder micturition
      contractions in rats. We used anesthetized male rats in three different age
      groups: young adult (4-5 months old), middle aged (6-9 months old), and aged (27
      30 months old). The bladder was expanded to produce isovolumetric rhythmic
      micturition contractions. Skin afferent fibers were activated for 1 min either by
      electrical stimulation (0.5 ms, 0.2-10 V, 0.1-10 Hz) of the cutaneous branch of
      the pudendal nerve (CBPN) or by gentle mechanical skin stimulation with an
      elastomer roller. When skin afferent nerves were activated electrically,
      micturition contractions were inhibited in a similar manner in all age groups,
      with long latency inhibition induced by excitation of Abeta fibers and short
      latency inhibition by additional Adelta and C fiber excitation (at 1-10 Hz). On
      the contrary, when skin afferent nerves were activated mechanically by rolling,
      latency of inhibition following rolling stimulation was prolonged in aged rats.
      Single unitary afferent nerve activity of low-threshold mechanoreceptors (LTMs)
      from the cutaneous nerve was recorded. The discharge rate during rolling was not
      significantly reduced in Abeta units but was much lower in Adelta and C units in
      aged rats (0.4 and 0.5 Hz, respectively) than in young adult rats (3 and 7 Hz).
      These results suggest that the neural mechanism that inhibits bladder micturition
      contractions by skin afferent input is well maintained in old age, but the early
      inhibition by gentle skin stimulation is decreased because of reduced responses
      of Adelta- and C-LTMs.

PMID- 29599703
TI  - SP8 Transcriptional Regulation of Cyclin D1 During Mouse Early Corticogenesis.
AB  - Multiple signals control the balance between proliferation and differentiation of
      neural progenitor cells during corticogenesis. A key point of this regulation is
      the control of G1 phase length, which is regulated by the Cyclin/Cdks complexes.
      Using genome-wide chromatin immunoprecipitation assay and mouse genetics, we have
      explored the transcriptional regulation of Cyclin D1 (Ccnd1) during the early
      developmental stages of the mouse cerebral cortex. We found evidence that SP8
      binds to the Ccnd1 locus on exon regions. In vitro experiments show SP8 binding
      activity on Ccnd1 gene 3'-end, and point to a putative role for SP8 in modulating
      PAX6-mediated repression of Ccnd1 along the dorso-ventral axis of the developing
      pallium, creating a medialLow-lateralHigh gradient of neuronal differentiation.
      Activation of Ccnd1 through the promoter/5'-end of the gene does not depend on
      SP8, but on betacatenin (CTNNB1). Importantly, alteration of the Sp8 level of
      expression in vivo affects Ccnd1 expression during early corticogenesis. Our
      results indicate that Ccnd1 regulation is the result of multiple signals and that
      SP8 is a player in this regulation, revealing an unexpected and potentially novel
      mechanism of transcriptional activation.

PMID- 29599704
TI  - Pacing Hippocampal Sharp-Wave Ripples With Weak Electric Stimulation.
AB  - Sharp-wave ripples (SWRs) are spontaneous neuronal population events that occur
      in the hippocampus during sleep and quiet restfulness, and are thought to play a
      critical role in the consolidation of episodic memory. SWRs occur at a rate of 30
      200 events per minute. Their overall abundance may, however, be reduced with
      aging and neurodegenerative disease. Here we report that the abundance of SWR
      within murine hippocampal slices can be increased by paced administration of a
      weak electrical stimulus, especially when the spontaneously occurring rate is low
      or compromised. Resultant SWRs have large variations in amplitude and ripple
      patterns, which are morphologically indistinguishable from those of spontaneous
      SWRs, despite identical stimulus parameters which presumably activate the same
      CA3 neurons surrounding the electrode. The stimulus intensity for reliably pacing
      SWRs is weaker than that required for inducing detectable evoked field potentials
      in CA1. Moreover, repetitive ~1 Hz stimuli with low intensity can reliably evoke
      thousands of SWRs without detectable LTD or "habituation." Our results suggest
      that weak stimuli may facilitate the spontaneous emergence of SWRs without
      significantly altering their characteristics. Pacing SWRs with weak electric
      stimuli could potentially be useful for restoring their abundance in the damaged
      hippocampus.

PMID- 29599706
TI  - Lipoprotein Lipase Is a Feature of Alternatively-Activated Microglia and May
      Facilitate Lipid Uptake in the CNS During Demyelination.
AB  - Severe demyelinating disorders of the central nervous system (CNS) such as
      multiple sclerosis (MS), can be devastating for many young lives. To date, the
      factors resulting in poor remyelination and repair are not well understood, and
      reparative therapies that benefit MS patients have yet to be developed. We have
      previously shown that the activity and abundance of Lipoprotein Lipase (LPL)-the
      rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoproteins-is
      increased in Schwann cells and macrophages following nerve crush injury in the
      peripheral nervous system (PNS), suggesting that LPL may help scavenge myelin
      derived lipids. We hypothesized that LPL may play a similar role in the CNS. To
      test this, mice were immunized with MOG35-55 peptide to induce experimental
      allergic encephalomyelitis (EAE). LPL activity was increased (p < 0.05) in the
      brain at 30 days post-injection, coinciding with partial remission of clinical
      symptoms. Furthermore, LPL abundance and activity was up-regulated (p < 0.05) at
      the transition between de- and re-myelination in lysolecithin-treated ex vivo
      cerebellar slices. Since microglia are the key immune effector cells of the CNS
      we determined the role of LPL in microglia. Lipid uptake was decreased (p <
      0.001) in LPL-deficient BV-2 microglial cells compared to WT. In addition, LPL
      deficient cells showed dramatically reduced expression of anti-inflammatory
      markers, YM1 (-22 fold, p < 0.001), and arginase 1 (Arg1; -265 fold, p < 0.001)
      and increased expression of pro-inflammatory markers, such as iNOS compared to WT
      cells (+53 fold, p < 0.001). This suggests that LPL is a feature of reparative
      microglia, further supported by the metabolic and inflammatory profile of LPL
      deficient microglia. Taken together, our data strongly suggest that LPL
      expression is a novel feature of a microglial phenotype that supports
      remyelination and repair through the clearance of lipid debris. This mechanism
      may be exploited to develop future reparative therapies for MS and primary
      neurodegenerative disorders (Alzheimer's disease (AD) and Parkinson's disease).

PMID- 29599707
TI  - Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4
      (ATF4) in Neurons and Promotes ATF4-Dependent Induction of Sesn2.
AB  - Activating transcription factor 4 (ATF4) plays important physiologic roles in the
      brain including regulation of learning and memory as well as neuronal survival
      and death. Yet, outside of translational regulation by the eIF2alpha-dependent
      stress response pathway, there is little information about how its levels are
      controlled in neurons. Here, we show that brain-derived neurotrophic factor
      (BDNF) promotes a rapid and sustained increase in neuronal ATF4 transcripts and
      protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB)
      signaling, but independent of levels of phosphorylated eIF2alpha. The elevation
      in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis
      revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes
      Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex
      1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a
      number of other known ATF4 targets including several with pro-apoptotic activity.
      The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to
      maintain this transcription factor at levels that provide neuroprotection and
      optimal brain function without risk of triggering neurodegeneration.

PMID- 29599708
TI  - Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality
      Control.
AB  - The deglycase and chaperone protein DJ-1 is pivotal for cellular oxidative stress
      responses and mitochondrial quality control. Mutations in PARK7, encoding DJ-1,
      are associated with early-onset familial Parkinson's disease and lead to
      pathological oxidative stress and/or disrupted protein degradation by the
      proteasome. The aim of this study was to gain insights into the pathogenic
      mechanisms of selected DJ-1 missense mutations, by characterizing protein-protein
      interactions, core parameters of mitochondrial function, quality control
      regulation via autophagy, and cellular death following dopamine accumulation. We
      report that the DJ-1M26I mutant influences DJ-1 interactions with SUMO-1, in turn
      enhancing removal of mitochondria and conferring increased cellular
      susceptibility to dopamine toxicity. By contrast, the DJ-1D149A mutant does not
      influence mitophagy, but instead impairs Ca2+ dynamics and free radical
      homeostasis by disrupting DJ-1 interactions with a mitochondrial accessory
      protein known as DJ-1-binding protein (DJBP/EFCAB6). Thus, individual DJ-1
      mutations have different effects on mitochondrial function and quality control,
      implying mutation-specific pathomechanisms converging on impaired mitochondrial
      homeostasis.

PMID- 29599709
TI  - Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in
      Rats during Sleep Deprivation by Inhibiting the Microglia Activation.
AB  - Background: Sleep deprivation (SD) plagues modern society due to the professional
      demands. It prevails in patients with mood and neuroinflammatory disorders.
      Although growing evidence suggests the improvement in the cognitive performance
      by psychostimulants during sleep-deprived conditions, the impending involved
      mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory
      changes might be due to the glial cells activation induced modulation of the
      inflammatory cytokines during SD, which could be improved by administering
      psychostimulants. The present study evaluated the role of caffeine/modafinil on
      SD-induced behavioral and inflammatory consequences. Methods: Adult male Sprague
      Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine
      (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once
      every day during SD. Rats were subjected to anxious and depressive behavioral
      evaluation after SD. Subsequently, blood and brain were collected for
      biochemical, immunohistochemical and molecular studies. Results: Sleep deprived
      rats presented an increased number of entries and time spent in closed arms in
      elevated plus maze test and decreased total distance traveled in the open field
      (OF) test. Caffeine/modafinil treatment significantly improved these anxious
      consequences. However, we did not observe substantial changes in immobility and
      anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated
      the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein
      expression in the hippocampus during SD. Similar outcomes were observed in blood
      plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the
      microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during
      SD, however, no significant increase in immunoreactivity of astrocytes was
      observed. Sholl analysis signified the improvement in the morphological
      alterations of astrocytes and microglia after caffeine/modafinil administration
      during SD. Stereological analysis demonstrated a significant improvement in the
      number of ionized calcium binding adapter molecule I (Iba-1) positive cells
      (different states) in different regions of the hippocampus after caffeine or
      modafinil treatment during SD without showing any significant change in total
      microglial cell number. Eventually, the correlation analysis displayed a positive
      relationship between anxiety, pro-inflammatory cytokines and activated microglial
      cell count during SD. Conclusion: The present study suggests the role of caffeine
      or modafinil in the amelioration of SD-induced inflammatory response and anxious
      behavior in rats. Highlights - SD induced mood alterations in rats. - Glial cells
      activated in association with the changes in the inflammatory cytokines. -
      Caffeine or modafinil improved the mood and restored inflammatory changes during
      SD. - SD-induced anxious behavior correlated with the inflammatory consequences.

PMID- 29599710
TI  - Topographic Organization of Inferior Olive Projections to the Zebrin II Stripes
      in the Pigeon Cerebellar Uvula.
AB  - This study was aimed at mapping the organization of the projections from the
      inferior olive (IO) to the ventral uvula in pigeons. The uvula is part of the
      vestibulocerebellum (VbC), which is involved in the processing of optic flow
      resulting from self-motion. As in other areas of the cerebellum, the uvula is
      organized into sagittal zones, which is apparent with respect to afferent inputs,
      the projection patterns of Purkinje cell (PC) efferents, the response properties
      of PCs and the expression of molecular markers such as zebrin II (ZII). ZII is
      heterogeneously expressed such that there are sagittal stripes of PCs with high
      ZII expression (ZII+), alternating with sagittal stripes of PCs with little to no
      ZII expression (ZII-). We have previously demonstrated that a ZII+/- stripe pair
      in the uvula constitutes a functional unit, insofar as the complex spike activity
      (CSA) of all PCs within a ZII+/- stripe pair respond to the same type of optic
      flow stimuli. In the present study we sought to map the climbing fiber (CF)
      inputs from the IO to the ZII+ and ZII- stripes in the uvula. We injected
      fluorescent Cholera Toxin B (CTB) of different colors (red and green) into ZII+
      and ZII- bands of functional stripe pair. Injections in the ZII+ and ZII- bands
      resulted in retrograde labeling of spatially separate, but adjacent regions in
      the IO. Thus, although a ZII+/- stripe pair represents a functional unit in the
      pigeon uvula, CF inputs to the ZII+ and ZII- stripes of a unit arise from
      separate regions of the IO.

PMID- 29599711
TI  - Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long
      Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female
      Offspring Prenatally Exposed to a High-Fat Diet.
AB  - A growing body of evidence suggests the consumption of high-fat diet (HFD) during
      pregnancy to model maternal obesity and the associated increase in oxidative
      stress (OS), might act as powerful prenatal stressors, leading to adult stress
      related metabolic or behavioral disorders. We hypothesized that administration of
      antioxidants throughout gestation might counteract the negative effects of
      prenatal exposure to metabolic challenges (maternal HFD feeding during pregnancy)
      on the developing fetus. In this study, female C57BL/6J mice were fed HFD for 13
      weeks (from 5-weeks of age until delivery) and were exposed to the N-acetyl
      cysteine (NAC) antioxidant from 10-weeks of age until right before delivery. Body
      weight of the offspring was assessed following birth, up to weaning and at
      adulthood. The metabolic, neuroendocrine and emotional profile of the adult
      offspring was tested at 3-months of age. Prenatal HFD increased mother's body
      weight and offspring's weight at the time of weaning, when administered in
      conjunction with NAC. In females, NAC administration reduced high levels of
      leptin resulting from prenatal HFD. Prenatal NAC administration also resulted in
      greater glucose tolerance and insulin sensitivity while increasing adiponectin
      levels, as well as increasing exploratory behavior, an effect accompanied by
      reduced plasma corticosterone levels in response to restraint stress. Analysis of
      glutathione levels in the hypothalamus and in brown adipose tissue indicates
      that, while HFD administration to pregnant dams led to reduced levels of
      glutathione in the offspring, as in the male hypothalamus, NAC was able to revert
      this effect and to increase glutathione levels both in the periphery (Brown
      Adipose Tissue, both males and females) and in the central nervous system
      (males). Overall, results from this study indicate that the body redox milieu
      should be tightly regulated during fetal life and that buffering OS during
      pregnancy can have important long-term consequences on metabolic and behavioral
      endpoints.

PMID- 29599712
TI  - Environmental Enrichment Expedites Acquisition and Improves Flexibility on a
      Temporal Sequencing Task in Mice.
AB  - Environmental enrichment (EE) via increased opportunities for voluntary exercise,
      sensory stimulation and social interaction, can enhance the function of and
      behaviours regulated by cognitive circuits. Little is known, however, as to how
      this intervention affects performance on complex tasks that engage multiple,
      definable learning and memory systems. Accordingly, we utilised the Olfactory
      Temporal Order Discrimination (OTOD) task which requires animals to recall and
      report sequence information about a series of recently encountered olfactory
      stimuli. This approach allowed us to compare animals raised in either enriched or
      standard laboratory housing conditions on a number of measures, including the
      acquisition of a complex discrimination task, temporal sequence recall accuracy
      (i.e., the ability to accurately recall a sequences of events) and acuity (i.e.,
      the ability to resolve past events that occurred in close temporal proximity), as
      well as cognitive flexibility tested in the style of a rule reversal and an Intra
      Dimensional Shift (IDS). We found that enrichment accelerated the acquisition of
      the temporal order discrimination task, although neither accuracy nor acuity was
      affected at asymptotic performance levels. Further, while a subtle enhancement of
      overall performance was detected for both rule reversal and IDS versions of the
      task, accelerated performance recovery could only be attributed to the shift-like
      contingency change. These findings suggest that EE can affect specific elements
      of complex, multi-faceted cognitive processes.

PMID- 29599713
TI  - Commentary: Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role
      for Ipsilateral Hemisphere in Motor Learning.

PMID- 29599714
TI  - Clustering Coefficients for Correlation Networks.
AB  - Graph theory is a useful tool for deciphering structural and functional networks
      of the brain on various spatial and temporal scales. The clustering coefficient
      quantifies the abundance of connected triangles in a network and is a major
      descriptive statistics of networks. For example, it finds an application in the
      assessment of small-worldness of brain networks, which is affected by attentional
      and cognitive conditions, age, psychiatric disorders and so forth. However, it
      remains unclear how the clustering coefficient should be measured in a
      correlation-based network, which is among major representations of brain
      networks. In the present article, we propose clustering coefficients tailored to
      correlation matrices. The key idea is to use three-way partial correlation or
      partial mutual information to measure the strength of the association between the
      two neighboring nodes of a focal node relative to the amount of pseudo
      correlation expected from indirect paths between the nodes. Our method avoids the
      difficulties of previous applications of clustering coefficient (and other)
      measures in defining correlational networks, i.e., thresholding on the
      correlation value, discarding of negative correlation values, the pseudo
      correlation problem and full partial correlation matrices whose estimation is
      computationally difficult. For proof of concept, we apply the proposed clustering
      coefficient measures to functional magnetic resonance imaging data obtained from
      healthy participants of various ages and compare them with conventional
      clustering coefficients. We show that the clustering coefficients decline with
      the age. The proposed clustering coefficients are more strongly correlated with
      age than the conventional ones are. We also show that the local variants of the
      proposed clustering coefficients (i.e., abundance of triangles around a focal
      node) are useful in characterizing individual nodes. In contrast, the
      conventional local clustering coefficients were strongly correlated with and
      therefore may be confounded by the node's connectivity. The proposed methods are
      expected to help us to understand clustering and lack thereof in correlational
      brain networks, such as those derived from functional time series and across
      participant correlation in neuroanatomical properties.

PMID- 29599715
TI  - DynaSim: A MATLAB Toolbox for Neural Modeling and Simulation.
AB  - DynaSim is an open-source MATLAB/GNU Octave toolbox for rapid prototyping of
      neural models and batch simulation management. It is designed to speed up and
      simplify the process of generating, sharing, and exploring network models of
      neurons with one or more compartments. Models can be specified by equations
      directly (similar to XPP or the Brian simulator) or by lists of predefined or
      custom model components. The higher-level specification supports arbitrarily
      complex population models and networks of interconnected populations. DynaSim
      also includes a large set of features that simplify exploring model dynamics over
      parameter spaces, running simulations in parallel using both multicore processors
      and high-performance computer clusters, and analyzing and plotting large numbers
      of simulated data sets in parallel. It also includes a graphical user interface
      (DynaSim GUI) that supports full functionality without requiring user
      programming. The software has been implemented in MATLAB to enable advanced
      neural modeling using MATLAB, given its popularity and a growing interest in
      modeling neural systems. The design of DynaSim incorporates a novel schema for
      model specification to facilitate future interoperability with other
      specifications (e.g., NeuroML, SBML), simulators (e.g., NEURON, Brian, NEST), and
      web-based applications (e.g., Geppetto) outside MATLAB. DynaSim is freely
      available at http://dynasimtoolbox.org. This tool promises to reduce barriers for
      investigating dynamics in large neural models, facilitate collaborative modeling,
      and complement other tools being developed in the neuroinformatics community.

PMID- 29599717
TI  - Gray Matter Network Disruptions and Regional Amyloid Beta in Cognitively Normal
      Adults.
AB  - The accumulation of amyloid plaques is one of the earliest pathological changes
      in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms.
      Examining associations between amyloid pathology and other early brain changes is
      critical for understanding the pathophysiological underpinnings of AD.
      Alterations in gray matter networks might already start at early preclinical
      stages of AD. In this study, we examined the regional relationship between
      amyloid aggregation measured with positron emission tomography (PET) and gray
      matter network measures in elderly subjects with subjective memory complaints.
      Single-subject gray matter networks were extracted from T1-weigthed structural
      MRI in cognitively normal subjects (n = 318, mean age 76.1 +/- 3.5, 64% female,
      28% amyloid positive). Degree, clustering, path length and small world properties
      were computed. Global and regional amyloid load was determined using [18F]
      Florbetapir PET. Associations between standardized uptake value ratio (SUVr)
      values and network measures were examined using linear regression models. We
      found that higher global SUVr was associated with lower clustering (beta = -0.12,
      p < 0.05), and small world values (beta = -0.16, p < 0.01). Associations were
      most prominent in orbito- and dorsolateral frontal and parieto-occipital regions.
      Local SUVr values showed less anatomical variability and did not convey
      additional information beyond global amyloid burden. In conclusion, we found that
      in cognitively normal elderly subjects, increased global amyloid pathology is
      associated with alterations in gray matter networks that are indicative of
      incipient network breakdown towards AD dementia.

PMID- 29599718
TI  - Re-evaluation of Adrenocorticotropic Hormone and Melanocyte Stimulating Hormone
      Activation of GPR139 in Vitro.
AB  - It is now well established that GPR139, a G-protein coupled receptor exclusively
      expressed in the brain and pituitary, is activated by the essential amino acids L
      tryptophan (L-Trp) and L-phenylalanine (L-Phe) via Galphaq-coupling. The in vitro
      affinity and potency values of L-Trp and L-Phe are within the physiological
      concentration ranges of L-Trp and L-Phe. A recent paper suggests that
      adrenocorticotropic hormone (ACTH), alpha and beta melanocyte stimulating
      hormones (alpha-MSH and beta-MSH) and derivatives alpha-MSH1-9/alpha-MSH1-10 can
      also activate GPR139 in vitro. We tested this hypothesis using guanosine 5'-O-(3
      [35S]thio)-triphosphate binding (GTPgammaS), calcium mobilization and [3H]JNJ
      63533054 radioligand binding assays. In the GTPgammaS binding assay, alpha-MSH,
      alpha-MSH1-9/alpha-MSH1-10, and beta-MSH had no effect on [35S]GTPgammaS
      incorporation in cell membranes expressing GPR139 up to 30 MUM in contrast to the
      concentration dependent activation produced by L-Trp, JNJ-63533054, and TC-09311
      (two small molecule GPR139 agonists). ACTH slightly decreased the basal level of
      [35S]GTPgammaS incorporation at 30 MUM. In the GPR139 radioligand binding assay,
      a moderate displacement of [3H]JNJ-63533054 binding by ACTH and beta-MSH was
      observed at 30 MUM (40 and 30%, respectively); alpha-MSH, alpha-MSH1-9/alpha-MSH1
      10 did not displace any specific binding at 30 MUM. In three different host cell
      lines stably expressing GPR139, alpha-MSH, and beta-MSH did not stimulate calcium
      mobilization in contrast to L-Trp, JNJ-63533054, and TC-09311. ACTH, alpha-MSH1
      9/alpha-MSH1-10 only weakly stimulated calcium mobilization at 30 MUM (<50% of
      EC100). We then co-transfected GPR139 with the three melanocortin (MC) receptors
      (MC3R, MC4R, and MC5R) to test the hypothesis that ACTH, alpha-MSH, and beta-MSH
      might stimulate calcium mobilization through a MCR/GPR139 interaction. All three
      MC peptides stimulated calcium response in cells co-transfected with GPR139 and
      MC3R, MC4R, or MC5R. The MC peptides did not stimulate calcium response in cells
      expressing MC3R or MC5R alone consistent with the Gs signaling transduction
      pathway of these receptors. In agreement with the previously reported multiple
      signaling pathways of MC4R, including Gq transduction pathway, the MC peptides
      produced a calcium response in cells expressing MC4R alone. Together, our
      findings do not support that GPR139 is activated by ACTH, alpha-MSH, and beta-MSH
      at physiologically relevant concentration but we did unravel an in vitro
      interaction between GPR139 and the MCRs.

PMID- 29599716
TI  - Atrophy in the Thalamus But Not Cerebellum Is Specific for C9orf72 FTD and ALS
      Patients - An Atlas-Based Volumetric MRI Study.
AB  - Background: The neuropathology of patients with frontotemporal dementia (FTD) or
      amyotrophic lateral sclerosis (ALS) due to a C9orf72 mutation is characterized by
      two distinct types of characteristic protein depositions containing either TDP-43
      or so-called dipeptide repeat proteins that extend beyond frontal and temporal
      regions. Thalamus and cerebellum seem to be preferentially affected by the
      dipeptide repeat pathology unique to C9orf72 mutation carriers. Objective: This
      study aimed to determine if mutation carriers showed an enhanced degree of
      thalamic and cerebellar atrophy compared to sporadic patients or healthy
      controls. Methods: Atlas-based volumetry was performed in 13 affected C9orf72
      FTD, ALS and FTD/ALS patients, 45 sporadic FTD and FTD/ALS patients and 19
      healthy controls. Volumes and laterality indices showing significant differences
      between mutation carriers and sporadic patients were subjected to binary logistic
      regression to determine the best predictor of mutation carrier status. Results:
      Compared to sporadic patients, mutation carriers showed a significant volume
      reduction of the thalamus, which was most striking in the occipital, temporal and
      prefrontal subregion of the thalamus. Disease severity measured by mini mental
      status examination (MMSE) and FTD modified Clinical Dementia Rating Scale Sum of
      Boxes (FTD-CDR-SOB) significantly correlated with volume reduction in the
      aforementioned thalamic subregions. No significant atrophy of cerebellar regions
      could be detected. A logistic regression model using the volume of the prefrontal
      and the laterality index of the occipital subregion of the thalamus as predictor
      variables resulted in an area under the curve (AUC) of 0.88 while a model using
      overall thalamic volume still resulted in an AUC of 0.82. Conclusion: Our data
      show that thalamic atrophy in C9orf72 mutation carriers goes beyond the expected
      atrophy in the prefrontal and temporal subregion and is in good agreement with
      the cortical atrophy pattern described in C9orf72 mutation carriers, indicating a
      retrograde degeneration of functionally connected regions. Clinical relevance of
      the detected thalamic atrophy is illustrated by a correlation with disease
      severity. Furthermore, the findings suggest MRI volumetry of the thalamus to be
      of high predictive value in differentiating C9orf72 mutation carriers from
      patients with sporadic FTD.

PMID- 29599720
TI  - Ethnopharmacology-A Bibliometric Analysis of a Field of Research Meandering
      Between Medicine and Food Science?
AB  - Background: The research into bioactive natural products of medicinal plants has
      a long tradition, but ethnopharmacology as a well-defined field of research has a
      relatively short history, only dating back 50 years. Aims: With the fast
      development of this field and its global importance especially in the fast
      developing economies of Asia it is timely to assess the most influential articles
      (as measured by citations) and to identify important drivers and research trends
      in this field. Methods: Scopus was searched to identify relevant articles which
      were assessed by all three authors. The 100 most cited articles were identified
      and analyzed. Bibliometric software (VOSviewer) was utilized to supplement the
      analysis and to generate a term map that visualized the citation patterns of the
      100 articles containing different terms. Results: Forty-four of the 100 articles
      are reviews. On average, each of the 100 articles had 632 citations and since
      publication was cited 43 times annually. The four core journals were Journal of
      Ethnopharmacology (n = 17), Food Chemistry (n = 7), Life Sciences (n = 5), and
      Journal of Agricultural and Food Chemistry (n = 4). Anti-oxidant effects appeared
      to be a recurring and highly cited topic, whereas the links into drug discovery
      and neuropharmacology seemed to be less strong. Numerous medicinal plants and
      functional foods were the foci of research, and the foci shifted when comparing
      pre-2000 and post-2000 publications (with the later involving a broader spectrum
      of plants and foods and a wider range of biological effects). Contributions
      largely came from Asia, and also from the Americas, Africa, and Oceania, besides
      Europe. Conclusion: We have identified and analyzed the 100 most-cited articles
      in ethnopharmacology. Within 50 years the field has gained a profile and while
      conventionally often linked to "traditional knowledge," drug discovery and some
      areas of pharmacology, this analysis highlights its emerging importance in the
      context of disease prevention (food science), but also the development of
      research driven by the needs and interests of the fast developing economies most
      notably of Asia.

PMID- 29599705
TI  - Of Men and Mice: Modeling the Fragile X Syndrome.
AB  - The Fragile X Syndrome (FXS) is one of the most common forms of inherited
      intellectual disability in all human societies. Caused by the transcriptional
      silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is
      characterized by a variety of symptoms, which range from mental disabilities to
      autism and epilepsy. More than 20 years ago, a first animal model was described,
      the Fmr1 knock-out mouse. Several other models have been developed since then,
      including conditional knock-out mice, knock-out rats, a zebrafish and a
      drosophila model. Using these model systems, various targets for potential
      pharmaceutical treatments have been identified and many treatments have been
      shown to be efficient in preclinical studies. However, all attempts to turn these
      findings into a therapy for patients have failed thus far. In this review, I will
      discuss underlying difficulties and address potential alternatives for our future
      research.

PMID- 29599719
TI  - Metabotropic Glutamate2 Receptors Play a Key Role in Modulating Head Twitches
      Induced by a Serotonergic Hallucinogen in Mice.
AB  - There is substantial evidence that glutamate can modulate the effects of 5
      hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of
      metabotropic glutamate2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we
      show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect
      of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2
      and mGlu3 receptor knockout (KO) as well as age-matched ICR (CD-1) wild type (WT)
      mice were administered (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)
      and observed for head twitch activity. DOI failed to produce significant head
      twitches in mGlu2 receptor KO mice at a dose 10-fold higher than the peak
      effective dose in WT or mGlu3 receptor KO mice. In addition, the mGlu2/3 receptor
      agonist LY379268, and the mGlu2 receptor positive allosteric modulator (PAM)
      CBiPES, potently blocked the HTR to DOI in WT and mGlu3 receptor KO mice.
      Conversely, the mGlu2/3 receptor antagonist LY341495 (10 mg/kg) increased the HTR
      produced by DOI (3 mg/kg) in mGlu3 receptor KO mice. Finally, the mGlu2 receptor
      potentiator CBiPES was able to attenuate the increase in the HTR produced by
      LY341495 in mGlu3 receptor KO mice. Taken together, all of these results are
      consistent with the hypothesis that that DOI-induced head twitches are modulated
      by mGlu2 receptor activation. These results also are in keeping with a critical
      autoreceptor function for mGlu2 receptors in the prefrontal cortex with
      differential effects of acute vs. chronic perturbation (e.g., constitutive mGlu2
      receptor KO mice). The robust attenuation of DOI-induced head twitches in the
      mGlu2 receptor KO mice appears to reflect the critical role of glutamate in
      ongoing regulation of 5-HT2A receptors in the prefrontal cortex. Future
      experiments with inducible knockouts for the mGlu2 receptor and/or selective
      mGlu3 receptor agonists/PAMs/antagonists could provide an important tools in
      understanding glutamatergic modulation of prefrontal cortical 5-HT2A receptor
      function.

PMID- 29599721
TI  - The Effect of a Competitive Futsal Match on T Lymphocyte Surface Receptor
      Signaling and Functions.
AB  - In this study, the lymphocyte activation status (surface expression of CD95,
      CD28, CD25, and CTLA-4), lymphocyte number, lymphocyte subpopulations, lymphocyte
      necrosis and/or apoptosis, and lymphocyte release of reactive oxygen species
      (ROS) were investigated in blood samples from 16 futsal athletes before and
      immediately following a competitive match. Lymphocytes were isolated from the
      blood samples, and the cellular parameters were assessed by flow cytometry. The
      futsal match induced lymphocytosis and lymphocyte apoptosis, as indicated by
      phosphatidylserine externalization, CD95 expression, and DNA fragmentation.
      Additionally, the competitive match induced the necrotic death of lymphocytes. No
      differences in the percentage of CD4+ and CD8+ T cells or in the T
      helper/suppressor profile between before and immediately after the match were
      observed. Additionally, after the futsal match, the CD95 and CD28 expression
      levels were decreased, and the lymphocytes spontaneously released higher levels
      of ROS. Regardless of the origin, the situation-specific knowledge of lymphocyte
      behavior obtained herein may facilitate the design of strategies to control the
      processes that result in infection and tissue injury and that subsequently
      decrease athletic performance.

PMID- 29599722
TI  - Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of
      Cardiorespiratory Fitness.
AB  - Markers of chronic inflammation increase with aging, and are associated with
      cardiovascular disease prevalence and mortality. Increases in fitness with
      exercise training have been associated with lower circulating concentrations of
      cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6])
      and higher circulating concentrations of anti-inflammatory cytokines (interleukin
      10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine
      responses to a single bout of exercise in healthy older individuals is unknown.
      We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha
      (TNF-alpha) and IL-10 to a bout of moderate-intensity continuous and higher
      intensity interval exercise between older individuals with higher and lower
      levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6+/-2.8 mL.kg
      1.min-1) and fourteen higher-fit participants (VO2peak: 37.4+/-5.9 mL.kg-1.min-1)
      completed three 24 min experimental protocols in a randomized order: (1) moderate
      intensity continuous exercise (40% of peak power output [PPO]); (2) higher
      intensity interval exercise (12 * 1 min intervals at 70% PPO separated by 1 min
      periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured
      at rest, immediately after, and during 90 min of recovery following exercise or
      control. Plasma IL-6 concentrations at baseline were greater in the higher-fit
      compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or
      TNF-alpha concentrations at baseline between groups. Plasma IL-6 and IL-10
      concentrations in both groups increased immediately after all protocols (IL-6: P
      = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10
      response between the exercise and non-exercise (control) protocols. After all
      protocols, no changes in plasma TNF-alpha concentrations were observed in either
      the higher- or lower-fit groups. In this study, basal concentrations of
      circulating IL-6 were elevated in older individuals with higher levels of
      cardiorespiratory fitness. However, changes in plasma cytokine concentrations
      after exercise were not different to changes after non-exercise control in both
      the lower- and higher-fit groups.

PMID- 29599723
TI  - Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus)
      Under Long-Term Hypersaline Stress.
AB  - The fish brain plays an important role in controlling growth, development,
      reproduction, and adaptation to environmental change. However, few studies stem
      from the perspective of whole transcriptome change in a fish brain and its
      response to long-term hypersaline stress. This study compares the differential
      transcriptomic responses of juvenile Nile tilapia (Oreochromis niloticus)
      maintained for 8 weeks in brackish water (16 practical salinity units, psu) and
      in freshwater. Fish brains from each treatment were collected for RNA-seq
      analysis to identify potential genes and pathways responding to hypersaline
      stress. A total of 27,089 genes were annotated, and 391 genes were expressed
      differently in the salinity treatment. Ten pathways containing 40 differentially
      expressed genes were identified in the tilapia brain. Antigen processing and
      presentation and phagosome were the two principally affected pathways in the
      immune system. Thirty-one of 40 genes were involved in various expressions
      associated with environmental information processing pathways such as neuroactive
      ligand-receptor interaction, cytokine-cytokine receptor interaction, the Jak-STAT
      signaling pathway, cell adhesion molecules (CAMs), and the PI3K-Akt signaling
      pathway, which are the upstream pathways for modulation of immunity and
      osmoregulation. The most-changed genes (>5-fold) were all down-regulated,
      including four growth hormone/prolactin gene families, i.e., prolactin precursor
      (-10.62), prolactin-1 (-11), somatotropin (-10.15), somatolactin-like (-6.18),
      and two other genes [thyrotropin subunit beta (-7.73) and gonadotropin subunit
      beta-2 (-5.06)] that stimulated prolactin release in tilapia. The downregulation
      pattern of these genes corroborates the decrease in tilapia immunity with
      increasing salinity and reveals an adaptive mechanism of tilapia to long-term
      hypersaline stress. Ovarian steroidogenesis, isoquinoline alkaloid biosynthesis,
      and phenylalanine metabolism are the three important pathways in the response of
      the fish to long-term hypersaline stress. This study has identified several
      pathways and relevant genes that are involved in salinity regulation in a
      euryhaline fish and provides insight into understanding regulatory mechanisms of
      fish to salinity change.

PMID- 29599724
TI  - Age-Predicted Maximal Heart Rate in Recreational Marathon Runners: A Cross
      Sectional Study on Fox's and Tanaka's Equations.
AB  - Age-based prediction equations of maximal heart rate (HRmax), such as the popular
      formulas Fox's 220-age, or Tanaka's 208-0.7 * age, have been widely used in
      various populations. Surprisingly, so far these equations have not been validated
      in marathon runners, despite the importance of the role of HRmax for training
      purposes in endurance running. The aim of the present study was to examine the
      validity of Fox and Tanaka equations in a large sample of women and men
      recreational marathon runners. Participants (n = 180, age 43.2 +/- 8.5 years,
      VO2max 46.8 mL/min/kg, finishers in at least one marathon during the last year)
      performed a graded exercise test on a treadmill, where HRmax was measured.
      Measured HRmax correlated largely with age in the total sample (r = -0.50, p <
      0.001), women (r = -0.60, p < 0.001) and men (r = -0.53, p < 0.001). In women, a
      large main effect of method on HRmax (p = 0.001, eta2 = 0.294) was shown with
      measured HRmax lower than Fox-HRmax (-4.8 bpm; -8.4, -1.3) and Tanaka-HRmax (-4.9
      bpm; -8.1, -1.8). In men, a moderate effect of assessment method on HRmax was
      found (p = 0.001, eta2 = 0.066) with measured HRmax higher than Fox-HRmax (+2.8;
      1.0, 4.6), Tanaka-HRmax higher than Fox-HRmax (+1.2; 0.7, 1.7). Based on these
      findings, it was concluded that Fox and Tanaka' formulas overestimated HRmax by
      ~5 bpm in women, whereas Fox underestimated HRmax in men by ~3 bpm. Thus, we
      recommend the further use of Tanaka's formula in men marathon runners. In
      addition, exercise physiologists and sport scientists should consider the
      observed differences among various assessment methods when performing exercise
      testing or prescribing training program relying on HR.

PMID- 29599725
TI  - Validity and Reliability of 10-Hz Global Positioning System to Assess In-line
      Movement and Change of Direction.
AB  - The objectives of the present study were to examine the validity and reliability
      of the 10 Hz Johan GPS unit in assessing in-line movement and change of
      direction. The validity was tested against the criterion measure of 200 m track
      and-field (track-and-field athletes, n = 8) and 20 m shuttle run endurance test
      (female soccer players, n = 20). Intra-unit and inter-unit reliability was tested
      by intra-class correlation coefficient (ICC) and coefficient of variation (CV),
      respectively. An analysis of variance examined differences between the GPS
      measurement and five laps of 200 m at 15 km/h, and t-test examined differences
      between the GPS measurement and 20 m shuttle run endurance test. The difference
      between the GPS measurement and 200 m distance ranged from -0.13 +/- 3.94 m (95%
      CI -3.42; 3.17) in the first lap to 2.13 +/- 2.64 m (95% CI -0.08; 4.33) in the
      fifth lap. A good intra-unit reliability was observed in 200 m (ICC = 0.833, 95%
      CI 0.535; 0.962). Inter-unit CV ranged from 1.31% (fifth lap) to 2.20% (third
      lap). The difference between the GPS measurement and 20 m shuttle run endurance
      test ranged from 0.33 +/- 4.16 m (95% CI -10.01; 10.68) in 11.5 km/h to 9.00 +/-
      5.30 m (95% CI 6.44; 11.56) in 8.0 km/h. A moderate intra-unit reliability was
      shown in the second and third stage of the 20 m shuttle run endurance test (ICC =
      0.718, 95% CI 0.222;0.898) and good reliability in the fifth, sixth, seventh and
      eighth (ICC = 0.831, 95% CI -0.229;0.996). Inter-unit CV ranged from 2.08% (11.5
      km/h) to 3.92% (8.5 km/h). Based on these findings, it was concluded that the 10
      Hz Johan system offers an affordable valid and reliable tool for coaches and
      fitness trainers to monitor training and performance.

PMID- 29599726
TI  - The Neural Correlates of Probabilistic Classification Learning in Obsessive
      Compulsive Disorder: A Pilot Study.
AB  - Individuals suffering from obsessive-compulsive disorder (OCD) have been found to
      show deficits in implicitly learning probabilistic associations between events.
      Neuroimaging studies have associated these implicit learning deficits in OCD
      individuals with aberrant activation of the striatal system. Recent behavioral
      studies have highlighted that probabilistic classification learning (PCL)
      deficits in OCD individuals only occur in a disorder-specific context, while PCL
      remains intact in a neutral context. The neural correlates of implicit learning
      in an OCD-specific context, however, have not yet been investigated. Using
      functional magnetic resonance imaging during a neutral (prediction of weather)
      and an OCD-specific variant (prediction of a virus epidemic) of a PCL paradigm,
      we assessed brain activity associated with implicit learning processes in 10
      participants with OCD and 10 matched healthy controls. Regions of interest (ROIs)
      were the striatum and the medial temporal lobe. ROI analyses revealed a
      significantly higher activity in the bilateral putamen and the left hippocampus
      of OCD participants as compared to healthy controls during both PCL tasks. The
      group differences could partly be subsumed under a group * task interaction
      effect with OCD participants showing a significantly higher activity than healthy
      controls in the left putamen and the left hippocampus in the OCD-specific task
      variant only. These results suggest a compensation of aberrant striatal activity
      by an augmented engagement of the explicit memory system particularly in a
      disorder-relevant context in OCD participants.

PMID- 29599727
TI  - Brain GABA and Glutamate Concentrations Following Chronic Gabapentin
      Administration: A Convenience Sample Studied During Early Abstinence From
      Alcohol.
AB  - Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production,
      can normalize GABA and Glu tone during early abstinence from alcohol, effectively
      treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic
      resonance spectroscopy, we tested the degree to which daily GBP alters regional
      brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals.
      Regional metabolite levels were compared between 13 recently abstinent alcohol
      dependent individuals who had received daily GBP for at least 1 week (GBP+) and
      25 matched alcohol-dependent individuals who had not received GBP (GBP-).
      Magnetic resonance spectra from up to five different brain regions were analyzed
      to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the
      parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in
      anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did
      not differ between GBP- and GBP+. However, in a subgroup of individuals matched
      on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal
      white matter (WM) than GBP-, comparable to concentrations found in light/non
      drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a
      higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at
      least 1 week was not associated with altered cortical GABA and Glu concentrations
      during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP
      for the treatment of alcohol dependence may work through reducing Glu in WM
      rather than increasing cortical GABA.

PMID- 29599728
TI  - Altered Resting State Effective Connectivity of Anterior Insula in Depression.
AB  - Depression has been associated with changes in both functional and effective
      connectivity of large scale brain networks, including the default mode network,
      executive network, and salience network. However, studies of effective
      connectivity by means of spectral dynamic causal modeling (spDCM) are still rare
      and the interaction between the different resting state networks has not been
      investigated in detail. Thus, we aimed at exploring differences in effective
      connectivity among eight right hemisphere brain areas-anterior insula, inferior
      frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate
      cortex, superior parietal lobe, amygdala, and hippocampus, between a group of
      healthy controls (N = 20) and medicated depressed patients (N = 20). We found
      that patients not only had significantly reduced strength of the connection from
      the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a
      significant connection between the amygdala and the anterior insula. Moreover,
      depression severity correlated with connectivity of the hippocampal node. In
      conclusion, the results from this resting state spDCM study support and enrich
      previous data on the role of the right anterior insula in the pathophysiology of
      depression. Furthermore, our findings add to the growing evidence of an
      association between depression severity and disturbances of the hippocampal
      function in terms of impaired connectivity with other brain regions.

PMID- 29599729
TI  - Efficacy of the Aussie Optimism Program: Promoting Pro-social Behavior and
      Preventing Suicidality in Primary School Students. A Randomised-Controlled Trial.
AB  - The efficacy of an enhanced version of the Aussie Optimism Program (AOP) was
      investigated in a cluster randomized controlled trial. Grade 6 students aged 10
      11 years of age (N = 2288) from 63 government primary schools in Perth, Western
      Australia, participated in the pre, post, and follow-up study. Schools were
      randomly assigned to one of three conditions: Aussie Optimism with teacher
      training, Aussie Optimism with teacher training plus coaching, or a usual care
      condition that received the regular Western Australian Health Education
      Curriculum. Students in the Aussie Optimism conditions received 20, 1-h lessons
      relating to social and interpersonal skills and optimistic thinking skills over
      the last 2 years of primary school. Parents in the active conditions received a
      parent information booklet each year, plus a self-directed program in Grade 7.
      Students and parents completed the Extended Strengths and Difficulties
      Questionnaire. Students who scored in the clinical range on the Emotional
      Symptoms Scale were given The Diagnostic Interview for Children and Adolescents
      IV, to assess suicidal ideation and behavior, and depressive and anxiety
      disorders. Results indicated that Aussie Optimism with teacher training plus
      coaching was associated with the best outcomes: a significant increase in student
      reported pro-social behavior from pre-test to post-test 1 (maintained at post
      test 2) and significantly lower incidence rates from suicidal ideation at post
      test 2 and follow-up. No significant intervention effects on anxiety and
      depressive disorders, and total difficulties were reported. These findings
      suggest that the AOP with teacher training along with coaching may have the
      potential to positively impact on suicidality and pro-social behavior in the pre
      adolescent years.

PMID- 29599730
TI  - Monolingual and Bilingual Infants' Ability to Use Non-native Tone for Word
      Learning Deteriorates by the Second Year After Birth.
AB  - Previous studies reported a non-native word learning advantage for bilingual
      infants at around 18 months. We investigated developmental changes in infant
      interpretation of sounds that aid in object mapping. Dutch monolingual and
      bilingual (exposed to Dutch and a second non-tone-language) infants' word
      learning ability was examined on two novel label-object pairings using syllables
      differing in Mandarin tones as labels (flat vs. falling). Infants aged 14-15
      months, regardless of language backgrounds, were sensitive to violations in the
      label-objects pairings when lexical tones were switched compared to when they
      were the same as habituated. Conversely at 17-18 months, neither monolingual nor
      bilingual infants demonstrated learning. Linking with existing literature,
      infants' ability to associate non-native tones with meanings may be related to
      tonal acoustic properties and/or perceptual assimilation to native prosodic
      categories. These findings provide new insights into the relation between infant
      tone perception, learning, and interpretative narrowing from a developmental
      perspective.

PMID- 29599731
TI  - Top-Down Prioritization of Salient Items May Produce the So-Called Stimulus
      Driven Capture.
AB  - The current study proposes that top-down attentional prioritization of salient
      items may produce the so-called stimulus-driven capture. To test this proposal,
      the "expectation-based paradigm" was designed on the basis of a visual search
      task. In Experiment 1, a task-irrelevant singleton frame was presented at the
      same location in 70% of the trials. The target was either presented at chance
      level within the singleton location, or away from it. In line with the singleton
      capture phenomenon, participants were faster in identifying the target when it
      appeared in the singleton location compared to non-singleton locations. However,
      leaving out the singleton frame in 30% of the trials led to a similar effect;
      participants were faster in identifying the target when it appeared in the
      expected singleton location compared to expected non-singletons locations (a
      "quasi-capture" effect). These results suggest that the participants allocated
      their attention to the expected singleton location, rather than that the
      singleton itself captured attention. In Experiment 2, the same task-irrelevant
      color singleton was presented in a random position in 70% of the trials. This
      color frame was shown as a non-singleton in all of the 30% singleton-absent
      multicolored trials. A similar facilitation effect was obtained when the target
      appeared in the expected singleton color frame compared to other frames, in
      singleton-absent trials as in singleton-present trials. These results further
      support the idea that instances of singleton capture can be explained by top-down
      attentional shifts toward singleton items. Theoretical implications of these
      results are discussed. Mostly, the study calls to consider the possibility that
      all sources of attentional control may be represented by a continuous variable of
      top-down control, including the category of "physical salience."

PMID- 29599732
TI  - Functions of Autobiographical Memory in Younger and Older Adults.
AB  - Functional approach to autobiographical memory (AM) posits its three broad
      functions: directive, self, and social. Although these functions are probably
      universal, life stage and gender variations are expected. This research builds on
      previous studies investigating the validity of Thinking About Life Experiences
      Questionnaire (TALE; Bluck and Alea, 2011). A sample of 365 adults (56% female,
      mean age 43.3 years), divided in 2 age cohorts (young: 18-45 years, old: 46-90
      years), used TALE, to rate their tendency of using AM for three different
      purposes, and measures of self-concept clarity, attachment in close relationships
      and time perspective. Confirmatory factor analysis of TALE confirmed the
      tripartite model of AM functions and further analysis showed partial factorial
      equivalence across age and gender groups. Young tend to use AM more for directing
      future behavior and social-bonding, while no age differences were found in the
      use of AM to serve self-function. As for gender variations, women tend to use AM
      more for directing their behavior, while no other gender differences in the use
      of AM were found. TALE showed good internal consistency and convergent validity
      of the three subscales. The theory-driven hypotheses that individuals with low
      self-concept clarity would use AM more often to serve a self-function, those with
      higher levels of attachment anxiety would use AM more often to serve a social
      function, and those past-oriented would use memory more often for directive
      purpose, were all confirmed. Also confirmed was the notion of Past Negative
      Orientation to be more related to the directive use of AM than Past Positive Time
      Orientation. Limitations and future directions are discussed.

PMID- 29599733
TI  - L2-L1 Translation Priming Effects in a Lexical Decision Task: Evidence From Low
      Proficient Korean-English Bilinguals.
AB  - One of the key issues in bilingual lexical representation is whether L1
      processing is facilitated by L2 words. In this study, we conducted two
      experiments using the masked priming paradigm to examine how L2-L1 translation
      priming effects emerge when unbalanced, low proficiency, Korean-English
      bilinguals performed a lexical decision task. In Experiment 1, we used a 150 ms
      SOA (50 ms prime duration followed by a blank interval of 100 ms) and found a
      significant L2-L1 translation priming effect. In contrast, in Experiment 2, we
      used a 60 ms SOA (50 ms prime duration followed by a blank interval of 10 ms) and
      found a null effect of L2-L1 translation priming. This finding is the first
      demonstration of a significant L2-L1 translation priming effect with unbalanced
      Korean-English bilinguals. Implications of this work are discussed with regard to
      bilingual word recognition models.

PMID- 29599734
TI  - Using Shakespeare's Sotto Voce to Determine True Identity From Text.
AB  - Little is known of the private life of William Shakespeare, but he is famous for
      his collection of plays and poems, even though many of the works attributed to
      him were published anonymously. Determining the identity of Shakespeare has
      fascinated scholars for 400 years, and four significant figures in English
      literary history have been suggested as likely alternatives to Shakespeare for
      some disputed works: Bacon, de Vere, Stanley, and Marlowe. A myriad of
      computational and statistical tools and techniques have been used to determine
      the true authorship of his works. Many of these techniques rely on basic
      statistical correlations, word counts, collocated word groups, or keyword
      density, but no one method has been decided on. We suggest that an alternative
      technique that uses word semantics to draw on personality can provide an accurate
      profile of a person. To test this claim, we analyse the works of Shakespeare,
      Christopher Marlowe, and Elizabeth Cary. We use Word Accumulation Curves,
      Hierarchical Clustering overlays, Principal Component Analysis, and Linear
      Discriminant Analysis techniques in combination with RPAS, a multi-faceted text
      analysis approach that draws on a writer's personality, or self to identify
      subtle characteristics within a person's writing style. Here we find that RPAS
      can separate the known authored works of Shakespeare from Marlowe and Cary.
      Further, it separates their contested works, works suspected of being written by
      others. While few authorship identification techniques identify self from the way
      a person writes, we demonstrate that these stylistic characteristics are as
      applicable 400 years ago as they are today and have the potential to be used
      within cyberspace for law enforcement purposes.

PMID- 29599735
TI  - On the Determinants and Outcomes of Passion for Playing Pokemon Go.
AB  - In 2016, Pokemon Go became the most popular smartphone game. Despite the
      increasing popularity of this augmented reality game, to date, no studies have
      investigated passion for playing Pokemon Go. On the theoretical basis of the
      Dualistic Model of Passion (DMP), our goal was to investigate the associations
      between Pokemon Go playing motives, passion, and impulsivity. A total of 621
      Pokemon Go players participated in the study (54.9% female; Mage = 22.6 years,
      SDage = 4.4). It was found that impulsivity was more strongly associated with
      obsessive passion (OP) than with harmonious passion (HP). HP was associated with
      adaptive motives (i.e., outdoor activity, social, recreation, and nostalgia),
      while OP was associated with less adaptive motives (i.e., fantasy, escape,
      boredom, competition, and coping). Therefore, in line with the DMP, HP and OP for
      playing Pokemon Go can predict an almost perfectly distinguished set of adaptive
      or maladaptive playing motives, and OP has a noteworthy relationship with
      impulsivity as a determinant.

PMID- 29599736
TI  - TIMSS 2011 Student and Teacher Predictors for Mathematics Achievement Explored
      and Identified via Elastic Net.
AB  - A substantial body of research has been conducted on variables relating to
      students' mathematics achievement with TIMSS. However, most studies have employed
      conventional statistical methods, and have focused on selected few indicators
      instead of utilizing hundreds of variables TIMSS provides. This study aimed to
      find a prediction model for students' mathematics achievement using as many TIMSS
      student and teacher variables as possible. Elastic net, the selected machine
      learning technique in this study, takes advantage of both LASSO and ridge in
      terms of variable selection and multicollinearity, respectively. A logistic
      regression model was also employed to predict TIMSS 2011 Korean 4th graders'
      mathematics achievement. Ten-fold cross-validation with mean squared error was
      employed to determine the elastic net regularization parameter. Among 162 TIMSS
      variables explored, 12 student and 5 teacher variables were selected in the
      elastic net model, and the prediction accuracy, sensitivity, and specificity were
      76.06, 70.23, and 80.34%, respectively. This study showed that the elastic net
      method can be successfully applied to educational large-scale data by selecting a
      subset of variables with reasonable prediction accuracy and finding new variables
      to predict students' mathematics achievement. Newly found variables via machine
      learning can shed light on the existing theories from a totally different
      perspective, which in turn propagates creation of a new theory or complement of
      existing ones. This study also examined the current scale development convention
      from a machine learning perspective.

PMID- 29599737
TI  - Development of the Sexual Minority Adolescent Stress Inventory.
AB  - Although construct measurement is critical to explanatory research and
      intervention efforts, rigorous measure development remains a notable challenge.
      For example, though the primary theoretical model for understanding health
      disparities among sexual minority (e.g., lesbian, gay, bisexual) adolescents is
      minority stress theory, nearly all published studies of this population rely on
      minority stress measures with poor psychometric properties and development
      procedures. In response, we developed the Sexual Minority Adolescent Stress
      Inventory (SMASI) with N = 346 diverse adolescents ages 14-17, using a
      comprehensive approach to de novo measure development designed to produce a
      measure with desirable psychometric properties. After exploratory factor analysis
      on 102 candidate items informed by a modified Delphi process, we applied item
      response theory techniques to the remaining 72 items. Discrimination and
      difficulty parameters and item characteristic curves were estimated overall,
      within each of 12 initially derived factors, and across demographic subgroups.
      Two items were removed for excessive discrimination and three were removed
      following reliability analysis. The measure demonstrated configural and scalar
      invariance for gender and age; a three-item factor was excluded for demonstrating
      substantial differences by sexual identity and race/ethnicity. The final 64-item
      measure comprised 11 subscales and demonstrated excellent overall (alpha = 0.98),
      subscale (alpha range 0.75-0.96), and test-retest (scale r > 0.99; subscale r
      range 0.89-0.99) reliabilities. Subscales represented a mix of proximal and
      distal stressors, including domains of internalized homonegativity, identity
      management, intersectionality, and negative expectancies (proximal) and social
      marginalization, family rejection, homonegative climate, homonegative
      communication, negative disclosure experiences, religion, and work domains
      (distal). Thus, the SMASI development process illustrates a method to incorporate
      information from multiple sources, including item response theory models, to
      guide item selection in building a psychometrically sound measure. We posit that
      similar methods can be used to improve construct measurement across all areas of
      psychological research, particularly in areas where a strong theoretical
      framework exists but existing measures are limited.

PMID- 29599738
TI  - Peer Learning in Instrumental Practicing.
AB  - In higher music education (HME), the notion of "private teaching, private
      learning" has a long tradition, where the learning part rests on the student's
      individual practicing between instrumental lessons. However, recent research
      suggests that collaborative learning among peers is beneficial in several
      aspects, such as sense of belonging, motivation and self-efficacy. This is
      consistent with the concept of vicarious learning. In this study, we conducted a
      survey among bachelor music students in church music, performance or music
      education programs enrolled in a music academy (N = 96), where parts of the
      questionnaire addressed peer learning and peer's influence on the students's
      instrumental practicing, and the degree of satisfaction with their practicing.
      These issues were seen in relation to gender, musical genre and study program.
      Overall, the students reported engaging in peer learning related to their
      instrumental practicing, to various degrees. This involved discussing practicing
      matters with peers, and practicing together with peers. However, student's
      reports of their views on peer learning, show that they perceive it more
      beneficial than the amount of time reported doing it would indicate. No
      significant gender differences were found, but students within improvised
      music/jazz engaged the most in peer learning, and church music students the
      least. Neither the degree of engaging in peer learning nor reported influence
      from peers correlated significantly with the degree of satisfaction. We discuss
      whether a general dissatisfaction is caused by being in a competitive learning
      environment combined with a privatized culture for learning. Finally, we suggest
      that collaborative forums for instrumental practicing within HME institutions can
      function as constructive and supportive arenas to enhance students learning and
      inner motivation.

PMID- 29599739
TI  - Illusory Motion Reproduced by Deep Neural Networks Trained for Prediction.
AB  - The cerebral cortex predicts visual motion to adapt human behavior to surrounding
      objects moving in real time. Although the underlying mechanisms are still
      unknown, predictive coding is one of the leading theories. Predictive coding
      assumes that the brain's internal models (which are acquired through learning)
      predict the visual world at all times and that errors between the prediction and
      the actual sensory input further refine the internal models. In the past year,
      deep neural networks based on predictive coding were reported for a video
      prediction machine called PredNet. If the theory substantially reproduces the
      visual information processing of the cerebral cortex, then PredNet can be
      expected to represent the human visual perception of motion. In this study,
      PredNet was trained with natural scene videos of the self-motion of the viewer,
      and the motion prediction ability of the obtained computer model was verified
      using unlearned videos. We found that the computer model accurately predicted the
      magnitude and direction of motion of a rotating propeller in unlearned videos.
      Surprisingly, it also represented the rotational motion for illusion images that
      were not moving physically, much like human visual perception. While the trained
      network accurately reproduced the direction of illusory rotation, it did not
      detect motion components in negative control pictures wherein people do not
      perceive illusory motion. This research supports the exciting idea that the
      mechanism assumed by the predictive coding theory is one of basis of motion
      illusion generation. Using sensory illusions as indicators of human perception,
      deep neural networks are expected to contribute significantly to the development
      of brain research.

PMID- 29599740
TI  - The Role of Emotion Regulation in Reducing Emotional Distortions of Duration
      Perception.
AB  - Emotional events, especially negative ones, are consistently reported to last
      longer than neutral events. Previous studies suggested that this distortion of
      duration perception is linked to arousal and attention bias in response to
      emotional events. Reappraisal and suppression, arguably the most effective
      strategies for emotion regulation, have been demonstrated to decrease such
      arousal and attention bias. The present study investigated whether reappraisal
      and suppression can reduce emotional distortions of duration perception. Seventy
      eight Chinese undergraduates were recruited as paid participants and randomly
      assigned to nonregulation, reappraisal, and suppression groups. Before they
      performed a temporal bisection task involving presentation of emotional pictures
      for different durations, the groups were each given one of three different sets
      of instructions requiring them to passively perceive, reappraise, or suppress the
      emotions of the pictures. The results indicated that the distortion of duration
      perception occurred only in the nonregulation group, suggesting that it can be
      effectively reduced by reappraisal and suppression.

PMID- 29599741
TI  - The Quest for an Alzheimer Therapy.
AB  - This mini-review considers three different approaches to the therapy and
      prevention of Alzheimer's disease (AD): replacement therapy, disease
      modification, and multi-level interventions. Each of these research frameworks
      has direct implications at the clinical level, leading to an emphasis on
      different time points of the AD continuum. While all perspectives continue to
      play an important role in current efforts to reach the ambitious target of an
      effective therapy or prevention of AD by 2025, it is clear that novel paradigms
      are needed, including new models of clinical trial design. This goal can only be
      accomplished by a concerted effort of academia, governmental agencies, and
      industry.

PMID- 29599742
TI  - The Video Head Impulse Test and the Influence of Daily Use of Spectacles to
      Correct a Refractive Error.
AB  - Objective: To determine the influence of daily use of spectacles to correct a
      refractive error, on the vestibulo-ocular reflex (VOR) gain measured with the
      video head impulse test (vHIT). Study design: This prospective study enrolled
      subjects between 18 and 80 years old with and without a refractive error.
      Subjects were classified into three groups: (1) contact lenses, (2) spectacles,
      and (3) control group without visual impairment. Exclusion criteria comprised
      ophthalmic pathology, history of vestibular disorders, and alternated use of
      spectacles and contact lenses in daily life. Corrective spectacles were removed
      seconds before testing. One examiner performed all vHIT's under standardized
      circumstances using the EyeSeeCam system. This system calculated the horizontal
      VOR gain for rightward and leftward head rotations separately. Results: No
      statistically significant difference was found in VOR gain between the control
      group (n = 16), spectacles group (n = 48), and contact lenses group (n = 15) (p =
      0.111). Both the spectacles group and contact lenses group showed no
      statistically significant correlation between VOR gain and amount of refractive
      error, for rightwards (p = 0.071) and leftwards (p = 0.716) head rotations. There
      was no statistical significant difference in VOR gain between testing monocularly
      or binocularly (p = 0.132) and between testing with or without wearing contact
      lenses (p = 0.800). Conclusion: In this study, VOR gain was not influenced by
      wearing corrective spectacles or contact lenses on a daily basis. Based on this
      study, no corrective measures are necessary when performing the vHIT on subjects
      with a refractive error, regardless of the way of correction.

PMID- 29599743
TI  - A Tool to Quantify the Functional Impact of Oscillopsia.
AB  - Background: Individuals with bilateral vestibular hypofunction (BVH) often report
      symptoms of oscillopsia during walking. Existing assessments of oscillopsia are
      limited to descriptions of severity and symptom frequency, neither of which
      provides a description of functional limitations attributed to oscillopsia. A
      novel questionnaire, the Oscillopsia Functional Impact scale (OFI) was developed
      to describe the impact of oscillopsia on daily life activities. Questions on the
      OFI ask how often individuals are able to execute specific activities considered
      to depend on gaze stability in an effort to link functional mobility impairments
      to oscillopsia for individuals with vestibular loss. Methods: Subjective reports
      of oscillopsia and balance confidence were recorded for 21 individuals with BVH
      and 48 healthy controls. Spearman correlation coefficients were calculated to
      determine the relationship between the OFI and oscillopsia visual analog scale
      (OS VAS), oscillopsia severity questionnaire (OSQ), and Activities-Specific
      Balance Confidence scale to demonstrate face validity. Chronbach's alpha was
      calculated to determine internal validity for the items of the OFI. A one-way
      MANOVA was conducted with planned post hoc paired t-tests for group differences
      on all oscillopsia questionnaires using a corrected alpha = 0.0125. Results: The
      OFI was highly correlated with measures of oscillopsia severity (OS VAS; r =
      0.69, p < 0.001) and frequency (OSQ; r = 0.84, p < 0.001) and also with the
      Activities-Specific Balance Confidence scale (r = -0.84, p < 0.001). Cronbach's
      alpha for the OFI was 0.97. Individuals with BVH scored worse on all measures of
      oscillopsia and balance confidence compared to healthy individuals (p's < 0.001).
      Conclusion: The OFI appears to capture the construct of oscillopsia in the
      context of functional mobility. Combining with oscillopsia metrics that quantify
      severity and frequency allows for a more complete characterization of the impact
      of oscillopsia on an individual's daily behavior. The OFI discriminated
      individuals with BVH from healthy individuals.

PMID- 29599744
TI  - Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.
AB  - Objective: The aim of this study is to identify the molecular defect of three
      unrelated individuals with late-onset predominant distal myopathy; to describe
      the spectrum of phenotype resulting from the contributing role of two variants in
      genes located on two different chromosomes; and to highlight the underappreciated
      complex forms of genetic myopathies. Patients and methods: Clinical and
      laboratory data of three unrelated probands with predominantly distal weakness
      manifesting in the sixth-seventh decade of life, and available affected and
      unaffected family members were reviewed. Next-generation sequencing panel, whole
      exome sequencing, and targeted analyses of family members were performed to
      elucidate the genetic etiology of the myopathy. Results: Genetic analyses
      detected two contributing variants located on different chromosomes in three
      unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T,
      p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The
      affected fraternal twin of one proband also carries both variants, while the
      unaffected family members harbor one or none. Two unrelated probands (family 1,
      II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that
      manifested with index extensor weakness; the other proband (family 2, I.1) has
      myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and
      distal weakness. Conclusion: The findings indicate that all the affected
      individuals have a myopathy associated with both variants in SQSTM1 and TIA1,
      respectively, suggesting that the two variants determine the phenotype and likely
      functionally interact. We speculate that the TIA1 variant is a modifier of the
      SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a
      novel genetic defect associated with myofibrillar myopathy and suggest to
      consider sequencing both genes in the molecular investigation of myopathy with
      rimmed vacuoles and myofibrillar myopathy although additional studies are needed
      to investigate the digenic nature of the disease.

PMID- 29599745
TI  - Treatment Modality and Quality Benchmarks of Aneurysmal Subarachnoid Hemorrhage
      at a Comprehensive Stroke Center.
AB  - Background: Aneurysmal subarachnoid hemorrhage (aSAH) is the most severe type of
      stroke. In 2012, the Joint Commission, in collaboration with the American Heart
      Association/American Stroke Association (AHA/ASA), launched the Advanced
      Certification for Comprehensive Stroke Centers (CSCs). This new level of
      certification was designed to promote higher standard of care for patients with
      complex stroke. Objective: The goal of this study was to examine the treatment
      modality and quality benchmarks of aSAH at one of the first five certified CSCs
      in the United States. Methods: Consecutive patients with aSAH at Cedars-Sinai
      Medical Center between April 1, 2012 and May 30, 2014 were included for this
      retrospective study. The ruptured aneurysm was treated with coiling or clipping
      within 24 h. All patients were managed per AHA guidelines. Discharge outcomes
      were assessed using modified Rankin Scale (mRS). The rate of aneurysm treatment,
      door-to-treatment time, rate of posttreatment rebleed, hospital length of stay
      (LOS), discharge outcome, and mortality rates were evaluated as quality
      indicators. Results: The median age (interquartile range) of the 118 patients
      with aSAH was 55 (19). Among them, 84 (71.2%) were females, 94 (79.7%) were
      transfers from outside hospitals, and 74 (62.7%) had Hunt and Hess grades 1-3.
      Sixty patients (50.8%) were treated with coiling, 52 (44.1%) with clipping, and 6
      (5.1%) untreated due to ictal cardiac arrest or severe comorbidities. The rate of
      aneurysm treatment was 95% (112/118) with median door-to-treatment time at 12.5
      (8.5) h and 0.9% (1/112) posttreatment rebleed. The median ICU and hospital LOS
      were 12.5 (7) and 17.0 (14.5) days, respectively. Coiling was associated with
      significantly shorter LOS than clipping. There were 59 patients (50%) with
      favorable outcome and 19 deaths (16.1%) at hospital discharge. There was no
      significant difference in discharge outcome between coiling and clipping.
      Conclusion: Care of aSAH at one of the early CSCs in the United States was
      associated with high rate of aneurysm treatment, fast door-to-treatment time, low
      posttreatment rebleed, excellent outcome, and low mortality rate. Coiling was
      associated with significant shorter LOS than clipping. There was no significant
      difference in discharge outcomes between treatment modalities.

PMID- 29599746
TI  - Peripheral Dopamine in Restless Legs Syndrome.
AB  - Objective/Background: Restless Legs Syndrome (RLS) is a dopamine-dependent
      disorder characterized by a strong urge to move. The objective of this study was
      to evalulate blood levels of dopamine and other catecholamines and blood D2
      subtype dopamine receptors (D2Rs) in RLS. Patients/Methods: Dopamine levels in
      blood samples from age-matched unmedicated RLS subjects, medicated RLS subjects
      and Controls were evaluated with high performance liquid chromatography and
      dopamine D2R white blood cell (WBC) expression levels were determined with
      fluorescence-activated cell sorting and immunocytochemistry. Results: Blood
      plasma dopamine levels, but not norepinepherine or epinephrine levels, were
      significantly increased in medicated RLS subjects vs unmedicated RLS subjects and
      Controls. The percentage of lymphocytes and monocytes expressing D2Rs differed
      between Control, RLS medicated and RLS unmedicated subjects. Total D2R expression
      in lymphocytes, but not monocytes, differed between Control, RLS medicated and
      RLS unmedicated subjects. D2Rs in lymphocytes, but not monocytes, were sensitive
      to dopamine in Controls only. Conclusion: Downregulation of WBCs D2Rs occurs in
      RLS. This downregulation is not reversed by medication, although commonly used
      RLS medications increase plasma dopamine levels. The insensitivity of monocytes
      to dopamine levels, but their downregulation in RLS, may reflect their utility as
      a biomarker for RLS and perhaps brain dopamine homeostasis.

PMID- 29599747
TI  - Circadian and Metabolic Perspectives in the Role Played by NADPH in Cancer.
AB  - Physiological activity in healthy conditions requires a coordinated interaction
      between the molecular circadian clock and the network of biochemical pathways. An
      important metabolic parameter in the interface between these two entities is the
      redox state. Among the redox coenzymes that regulate the fluxes of enzymatic
      reactions is the NADP+/NADPH pair. Indeed, the main biosynthetic pathways need
      NADPH to serve as an electron donor for cellular anabolic transformations. The
      existence of a metabolic circadian clock is well established, and it was first
      identified in mammalian red blood cells. The metabolic circadian clock is
      independent of transcriptional activity and is sustained by the enzymatic complex
      peroxiredoxin/thioredoxin/NADPH. This complex shows 24-h redox fluctuations
      metabolizing H2O2 in various tissues and species (fungi, insects, and mammals).
      Although this NADPH-sensitive metabolic clock is autonomous in erythrocytes that
      lack a nucleus, it functions in concert with the transcriptional circadian clock
      in other cell types to accomplish the task of timing cellular physiology. During
      carcinogenesis, circadian alterations influence cell cycle onset and promote
      tumoral growth. These alterations also deregulate cellular energetics through a
      process known as aerobic glycolysis, or the Warburg effect. The Warburg effect is
      a typical response of cancer cells in which the metabolism turns into glycolysis
      even in the presence of functional mitochondria. This alteration has been
      interpreted as a cellular strategy to increase biomass during cancer, and one of
      its main factors is the availability of NADPH. This minireview explores the
      potential role of NADPH as a circadian and cancer-promoting metabolite.

PMID- 29599748
TI  - Polyostotic Fibrous Dysplasia With and Without McCune-Albright Syndrome-Clinical
      Features in a Nordic Pediatric Cohort.
AB  - Objective: Fibrous dysplasia (FD) presents as skeletal lesions in which normal
      bone is replaced by abnormal fibrous tissue due to mosaic GNAS mutation. McCune
      Albright syndrome (MAS) refers to FD combined with skin (cafe-au-lait) and
      endocrine manifestations. This study describes the clinical childhood
      manifestations of polyostotic FD and MAS in a Nordic cohort. Patients and design:
      We retrospectively reviewed a cohort of pediatric patients (n = 16) with
      polyostotic FD with or without MAS diagnosed and followed in two Nordic Pediatric
      tertiary clinics between 1996 and 2017. Results: Half of the 16 patients with
      polyostotic FD presented with MAS. All patients with MAS (n = 8) had cafe-au-lait
      spots, and either gonadotropin-independent precocious puberty (PP) (girls; n = 5)
      or abnormal testicle structure (boys, n = 3). None manifested hyperthyroidism or
      growth hormone excess. Mild hypophosphatemia was common (11/16), but none had
      signs of hypophosphatemic rickets. Craniofacial bone involvement was found in 12
      patients (75%); in 5 of these, skeletal lesions were limited to craniofacial
      area. One child with craniofacial disease had lost vision due to optic nerve
      damage. Eleven (69%) patients had sustained a fracture at FD lesion, over half of
      them requiring surgical fixation of the fracture, most commonly in the proximal
      femur. The first symptoms leading to FD/MAS diagnosis included skull/facial
      asymmetry (n = 4), PP (n = 3), abnormal gait (n = 3), pathologic fracture (n =
      3), wide-spread cafe-au-lait spots (n = 1), headache (n = 1), and vision loss (n
      = 1). Conclusion: Polyostotic FD and MAS remain diagnostic and therapeutic
      challenges because of the broad clinical spectrum. Recurrent fractures, pain, and
      even vision loss may impair the quality of life in children with FD.

PMID- 29599749
TI  - miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b
      and Activating Ras-MAPK Signal.
AB  - Preeclampsia is a pregnancy-specific complication defined as newly onset
      gestational hypertension and proteinuria. Deficiency in placental development is
      considered as the predominant cause of preeclampsia. Our previous study found
      that the expression of miR-518b increased significantly in the preeclamptic
      placentas, indicating the potential participation of this small RNA in the
      occurrence of preeclampsia. In this study, data analysis using multiple databases
      predicted Rap1b as a candidate target of miR-518b. An evident decrease in Rap1b
      expression was observed in preeclamptic placentas when compared with the control
      placentas, which was negatively correlated with the level of miR-518b. Based on
      the data of in situ hybridization and immunohistochemistry showing that Rap1b
      exhibited similar localization with miR-518b in villous cytotrophoblast cells and
      column trophoblasts, we further explored their function in regulating trophoblast
      cell proliferation. In HTR8/SVneo cells, exogenous transfection of miR-518b
      reduced the expression of Rap1b, and dual-luciferase reporter assay validated
      Rap1b as the direct target of miR-518b. The small RNA could increase the BrdU
      incorporation and the ratio of cells at S phase, and enhance the phosphorylation
      of Raf-1 and ERK1/2. Such growth-promoting effect could be efficiently reversed
      by Rap1b overexpression. The data indicate that miR-518b can promote trophoblast
      cell proliferation via Rap1b-Ras-MAPK pathway, and the aberrant upregulation of
      miR-518b in preeclamptic placenta may contribute to the excessive trophoblast
      proliferation. The study provides new evidence to further understand the etiology
      of preeclampsia.

PMID- 29599750
TI  - Postoperative Neck Ultrasonography Surveillance After Thyroidectomy in Patients
      With Medullary Thyroid Carcinoma: A Multicenter Study.
AB  - Background: For detecting tumor recurrence of medullary thyroid carcinoma (MTC)
      in the neck, an appropriate frequency and interval of postoperative
      ultrasonography (US) surveillance remains unclear. This study aimed to assess an
      appropriate interval and frequency of postoperative neck US surveillance for
      detecting tumor recurrence in patients who had undergone thyroid surgery due to
      MTC. Methods: A total of 86 patients who had undergone thyroid surgery for the
      treatment of MTC and had at least one postoperative US follow-up examination at
      any of nine affiliated hospitals were included. Postoperative follow-up US,
      clinical, and histopathological results of patients were reviewed. The tumor
      recurrence/persistence rate of MTC was investigated, and the interval and session
      number of postoperative follow-up US and clinicopathologic factors were compared
      between tumor recurrence/persistence and non-recurrence groups. Results: Of the
      86 patients, 22 (25.6%) showed tumor recurrence/persistence. Of the 22 patients
      with tumor recurrence/persistence, 11 (50%) showed structural
      recurrence/persistence in the neck on follow-up US. In these 11 patients, the
      mean interval and session number of postoperative follow-up US between initial
      surgery and the first US detection of recurrence/persistence was 41.3 +/- 39.3
      months (range, 6-128 months) and 2.6 +/- 2.3 (range, 1-8), respectively. On
      follow-up US, 6 (54.5%, 6/11) were diagnosed with tumor recurrence/persistence
      within 3 years of the initial surgery. Tumor recurrence/persistence was
      significantly correlated with TNM stage (p < 0.001) and multiplicity/bilaterality
      (p = 0.013). Conclusion: For detecting MTC recurrence/persistence, postoperative
      US surveillance at 1-year intervals may be sufficient within the first 3 years
      after thyroid surgery, but depending on the presence of relevant risk factors,
      annual or biannual US surveillance may be recommendable for 4-10 years after
      thyroid surgery.

PMID- 29599751
TI  - Circadian Rhythms and Clock Genes in Reproduction: Insights From Behavior and the
      Female Rabbit's Brain.
AB  - Clock gene oscillations are necessary for a successful pregnancy and parturition,
      but little is known about their function during lactation, a period demanding
      from the mother multiple physiological and behavioral adaptations to fulfill the
      requirements of the offspring. First, we will focus on circadian rhythms and
      clock genes in reproductive tissues mainly in rodents. Disruption of circadian
      rhythms or proper rhythmic oscillations of clock genes provoke reproductive
      problems, as found in clock gene knockout mice. Then, we will focus mainly on the
      rabbit doe as this mammal nurses the young just once a day with circadian
      periodicity. This daily event synchronizes the behavior and the activity of
      specific brain regions critical for reproductive neuroendocrinology and maternal
      behavior, like the preoptic area. This region shows strong rhythms of the PER1
      protein (product of the Per1 clock gene) associated with circadian nursing.
      Additionally, neuroendocrine cells related to milk production and ejections are
      also synchronized to daily nursing. A threshold of suckling is necessary to
      entrain once a day nursing; this process is independent of milk output as even
      virgin does (behaving maternally following anosmia) can display circadian nursing
      behavior. A timing motivational mechanism may regulate such behavior as
      mesolimbic dopaminergic cells are entrained by daily nursing. Finally, we will
      explore about the clinical importance of circadian rhythms. Indeed, women in
      chronic shift-work schedules show problems in their menstrual cycles and
      pregnancies and also have a high risk of preterm delivery, making this an
      important field of translational research.

PMID- 29599752
TI  - Transcriptional Response of Staphylococcus aureus to Sunlight in Oxic and Anoxic
      Conditions.
AB  - The transcriptional response of Staphylococcus aureus strain Newman to sunlight
      exposure was investigated under both oxic and anoxic conditions using RNA
      sequencing to gain insight into potential mechanisms of inactivation. S. aureus
      is a pathogenic bacterium detected at recreational beaches which can cause
      gastrointestinal illness and skin infections, and is of increasing public health
      concern. To investigate the S. aureus photostress response in oligotrophic
      seawater, S. aureus cultures were suspended in seawater and exposed to full
      spectrum simulated sunlight. Experiments were performed under oxic or anoxic
      conditions to gain insight into the effects of oxygen-mediated and non-oxygen
      mediated inactivation mechanisms. Transcript abundance was measured after 6 h of
      sunlight exposure using RNA sequencing and was compared to transcript abundance
      in paired dark control experiments. Culturable S. aureus decayed following
      biphasic inactivation kinetics with initial decay rate constants of 0.1 and 0.03
      m2 kJ-1 in oxic and anoxic conditions, respectively. RNA sequencing revealed that
      71 genes had different transcript abundance in the oxic sunlit experiments
      compared to dark controls, and 18 genes had different transcript abundance in the
      anoxic sunlit experiments compared to dark controls. The majority of genes showed
      reduced transcript abundance in the sunlit experiments under both conditions.
      Three genes (ebpS, NWMN_0867, and NWMN_1608) were found to have the same
      transcriptional response to sunlight between both oxic and anoxic conditions. In
      the oxic condition, transcripts associated with porphyrin metabolism, nitrate
      metabolism, and membrane transport functions were increased in abundance during
      sunlight exposure. Results suggest that S. aureus responds differently to oxygen
      dependent and oxygen-independent photostress, and that endogenous
      photosensitizers play an important role during oxygen-dependent indirect
      photoinactivation.

PMID- 29599753
TI  - Multiple Modes of Nematode Control by Volatiles of Pseudomonas putida 1A00316
      from Antarctic Soil against Meloidogyne incognita.
AB  - Pseudomonas putida 1A00316 isolated from Antarctic soil showed nematicidal
      potential for biological control of Meloidogyne incognita; however, little was
      known about whether strain 1A00316 could produce volatile organic compounds
      (VOCs), and if they had potential for use in biological control against M.
      incognita. In this study, VOCs produced by a culture filtrate of P. putida
      1A00316 were evaluated by in vitro experiments in three-compartment Petri dishes
      and 96-well culture plates. Our results showed that M. incognita juveniles
      gradually reduced their movement within 24-48 h of incubation with mortality
      ranging from 6.49 to 86.19%, and mostly stopped action after 72 h. Moreover, egg
      hatching in culture filtrates of strain 1A00316 was much reduced compared to that
      in sterile distilled water or culture medium. Volatiles from P. putida 1A00316
      analysis carried out by solid-phase micro-extraction gas chromatography-mass
      spectrometry (SPME-GC/MS) included dimethyl-disulfide, 1-undecene, 2-nonanone, 2
      octanone, (Z)-hexen-1-ol acetate, 2-undecanone, and 1-(ethenyloxy)-octadecane. Of
      these, dimethyl-disulfide, 2-nonanone, 2-octanone, (Z)-hexen-1-ol acetate, and 2
      undecanone had strong nematicidal activity against M. incognita J2 larvae by
      direct-contact in 96-well culture plates, and only 2-undecanone acted as a
      fumigant. In addition, the seven VOCs inhibited egg hatching of M. incognita both
      by direct-contact and by fumigation. All of the seven VOCs repelled M. incognita
      J2 juveniles in 2% water agar Petri plates. These results show that VOCs from
      strain 1A00316 act on different stages in the development of M. incognita via
      nematicidal, fumigant, and repellent activities and have potential for
      development as agents with multiple modes of control of root-knot nematodes.

PMID- 29599754
TI  - Generalized Growth of Estuarine, Household and Clinical Isolates of Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen of particular concern to
      immune-compromised people, such as cystic fibrosis patients and burn victims.
      These bacteria grow in built environments including hospitals and households, and
      in natural environments such as rivers and estuaries. However, there is
      conflicting evidence whether recent environments like the human lung and open
      ocean affect P. aeruginosa growth performance in alternate environments. We
      hypothesized that bacteria recently isolated from dissimilar habitats should grow
      differently in media containing artificial versus natural resources. To test this
      idea, we examined growth of P. aeruginosa isolates from three environments
      (estuary, household, and clinic) in three media types: minimal-glucose lab
      medium, and media prepared from sugar maple leaves or big bluestem grass. We used
      automated spectrophotometry to measure high-resolution growth curves for all
      isolate by media combinations, and studied two fitness parameters: growth rate
      and maximum population density. Results showed high variability in growth rate
      among isolates, both overall and in its dependence on assay media, but this
      variability was not associated with habitat of isolation. In contrast, total
      growth (change in absorbance over the experiment) differed overall among habitats
      of isolation, and there were media-specific differences in mean total growth
      among habitats of isolation, and in among-habitat variability in the media
      specific response. This was driven primarily by greater total growth of estuary
      isolates when compared with those from other habitats of origin, and greater
      media-specific variability among household isolates than those from other
      habitats of origin. Taken together, these results suggest that for growth rate P.
      aeruginosa bacteria appear to be broad generalists without regard to current or
      recent habitat, whereas for total growth a signature of recent ecological history
      can be detected.

PMID- 29599755
TI  - Analyzing AbrB-Knockout Effects through Genome and Transcriptome Sequencing of
      Bacillus licheniformis DW2.
AB  - As an industrial bacterium, Bacillus licheniformis DW2 produces bacitracin which
      is an important antibiotic for many pathogenic microorganisms. Our previous study
      showed AbrB-knockout could significantly increase the production of bacitracin.
      Accordingly, it was meaningful to understand its genome features, expression
      differences between wild and AbrB-knockout (DeltaAbrB) strains, and the
      regulation of bacitracin biosynthesis. Here, we sequenced, de novo assembled and
      annotated its genome, and also sequenced the transcriptomes in three growth
      phases. The genome of DW2 contained a DNA molecule of 4,468,952 bp with 45.93% GC
      content and 4,717 protein coding genes. The transcriptome reads were mapped to
      the assembled genome, and obtained 4,102~4,536 expressed genes from different
      samples. We investigated transcription changes in B. licheniformis DW2 and showed
      that DeltaAbrB caused hundreds of genes up-regulation and down-regulation in
      different growth phases. We identified a complete bacitracin synthetase gene
      cluster, including the location and length of bacABC, bcrABC, and bacT, as well
      as their arrangement. The gene cluster bcrABC were significantly up-regulated in
      DeltaAbrB strain, which supported the hypothesis in previous study of bcrABC
      transporting bacitracin out of the cell to avoid self-intoxication, and was
      consistent with the previous experimental result that DeltaAbrB could yield more
      bacitracin. This study provided a high quality reference genome for B.
      licheniformis DW2, and the transcriptome data depicted global alterations across
      two strains and three phases offered an understanding of AbrB regulation and
      bacitracin biosynthesis through gene expression.

PMID- 29599756
TI  - Mesobuthus Venom-Derived Antimicrobial Peptides Possess Intrinsic
      Multifunctionality and Differential Potential as Drugs.
AB  - Animal venoms are a mixture of peptides and proteins that serve two basic
      biological functions: predation and defense against both predators and microbes.
      Antimicrobial peptides (AMPs) are a common component extensively present in
      various scorpion venoms (herein abbreviated as svAMPs). However, their roles in
      predation and defense against predators and potential as drugs are poorly
      understood. Here, we report five new venom peptides with antimicrobial activity
      from two Mesobuthus scorpion species. These alpha-helical linear peptides
      displayed highly bactericidal activity toward all the Gram-positive bacteria used
      here but differential activity against Gram-negative bacteria and fungi. In
      addition to the antibiotic activity, these AMPs displayed lethality to houseflies
      and hemotoxin-like toxicity on mice by causing hemolysis, tissue damage and
      inducing inflammatory pain. Unlike AMPs from other origins, these venom-derived
      AMPs seem to be unsuitable as anti-infective drugs due to their high hemolysis
      and low serum stability. However, MeuTXKbeta1, a known two-domain Mesobuthus AMP,
      is an exception since it exhibits high activity toward antibiotic resistant
      Staphylococci clinical isolates with low hemolysis and high serum stability. The
      findings that the classical AMPs play predatory and defensive roles indicate that
      the multifunctionality of scorpion venom components is an intrinsic feature
      likely evolved by natural selection from microbes, prey and predators of
      scorpions. This definitely provides an excellent system in which one can study
      how a protein adaptively evolves novel functions in a new environment. Meantimes,
      new strategies are needed to remove the toxicity of svAMPs on eukaryotic cells
      when they are used as leads for anti-infective drugs.

PMID- 29599757
TI  - Interplay Between Capsule Expression and Uracil Metabolism in Streptococcus
      pneumoniae D39.
AB  - Pyrimidine nucleotides play an important role in the biosynthesis of activated
      nucleotide sugars (NDP-sugars). NDP-sugars are the precursors of structural
      polysaccharides in bacteria, including capsule, which is a major virulence factor
      of the human pathogen S. pneumoniae. In this work, we identified a spontaneous
      non-reversible mutant of strain D39 that displayed a non-producing capsule
      phenotype. Whole-genome sequencing analysis of this mutant revealed several non
      synonymous single base modifications, including in genes of the de novo synthesis
      of pyrimidines and in the -10 box of capsule operon promoter (Pcps). By directed
      mutagenesis we showed that the point mutation in Pcps was solely responsible for
      the drastic decrease in capsule expression. We also demonstrated that D39
      subjected to uracil deprivation shows increased biomass and decreased Pcps
      activity and capsule amounts. Importantly, Pcps expression is further decreased
      by mutating the first gene of the de novo synthesis of pyrimidines, carA. In
      contrast, the absence of uracil from the culture medium showed no effect on the
      spontaneous mutant strain. Co-cultivation of the wild-type and the mutant strain
      indicated a competitive advantage of the spontaneous mutant (non-producing
      capsule) in medium devoid of uracil. We propose a model in that uracil may act as
      a signal for the production of different capsule amounts in S. pneumoniae.

PMID- 29599758
TI  - Metatranscriptomics and Amplicon Sequencing Reveal Mutualisms in Seagrass
      Microbiomes.
AB  - Terrestrial plants benefit from many well-understood mutualistic relationships
      with root- and leaf-associated microbiomes, but relatively little is known about
      these relationships for seagrass and other aquatic plants. We used 16S rRNA gene
      amplicon sequencing and metatranscriptomics to assess potential mutualisms
      between microorganisms and the seagrasses Zostera marina and Zostera japonica
      collected from mixed beds in Netarts Bay, OR, United States. The phylogenetic
      composition of leaf-, root-, and water column-associated bacterial communities
      were strikingly different, but these communities were not significantly different
      between plant species. Many taxa present on leaves were related to organisms
      capable of consuming the common plant metabolic waste product methanol, and of
      producing agarases, which can limit the growth of epiphytic algae. Taxa present
      on roots were related to organisms capable of oxidizing toxic sulfur compounds
      and of fixing nitrogen. Metatranscriptomic sequencing identified expression of
      genes involved in all of these microbial metabolic processes at levels greater
      than typical water column bacterioplankton, and also identified expression of
      genes involved in denitrification and in bacterial synthesis of the plant growth
      hormone indole-3-acetate. These results provide the first evidence using
      metatranscriptomics that seagrass microbiomes carry out a broad range of
      functions that may benefit their hosts, and imply that microbe-plant mutualisms
      support the health and growth of aquatic plants.

PMID- 29599759
TI  - Emergence of CD4+ and CD8+ Polyfunctional T Cell Responses Against Immunodominant
      Lytic and Latent EBV Antigens in Children With Primary EBV Infection.
AB  - Long term carriers were shown to generate robust polyfunctional T cell (PFC)
      responses against lytic and latent antigens of Epstein-Barr virus (EBV). However,
      the time of emergence of PFC responses against EBV antigens, pattern of
      immunodominance and difference between CD4+ and CD8+ T cell responses during
      various stages of EBV infection are not clearly understood. A longitudinal study
      was performed to assess the development of antigen-specific PFC responses in
      children diagnosed to have primary symptomatic (infectious mononucleosis [IM])
      and asymptomatic (AS) EBV infection. Evaluation of IFN-gamma secreting CD8+ T
      cell responses upon stimulation by HLA class I-specific peptides of EBV lytic and
      latent proteins by ELISPOT assay followed by assessment of CD4+ and CD8+ PFC
      responses upon stimulation by a panel of overlapping EBV peptides for co
      expression of IFN-gamma, TNF-alpha, IL-2, perforin and CD107a by flow cytometry
      were performed. Cytotoxicity of T cells against autologous lymphoblastoid cell
      lines (LCLs) as well as EBV loads in PBMC and plasma were also determined. Both
      IM and AS patients had elevated PBMC and plasma viral loads which declined
      steadily during a 12-month period from the time of diagnosis whilst decrease in
      the magnitude of CD8+ T cell responses toward EBV lytic peptides in contrast to
      increase toward latent peptides was shown with no significant difference between
      those of IM and AS patients. Both lytic and latent antigen-specific CD4+ and CD8+
      T cells demonstrated polyfunctionality (defined as greater or equal to three
      functions) concurrent with enhanced cytotoxicity against autologous LCLs and
      steady decrease in plasma and PBMC viral loads over time. Immunodominant peptides
      derived from BZLF1, BRLF1, BMLF1 and EBNA3A-C proteins induced the highest
      proportion of CD8+ as well as CD4+ PFC responses. Diverse functional subtypes of
      both CD4+ and CD8+ PFCs were shown to emerge at 6-12 months. In conclusion, EBV
      antigen-specific CD4+ and CD8+ PFC responses emerge during the first year of
      primary EBV infection, with greatest responses toward immunodominant epitopes in
      both lytic and latent proteins, correlating to steady decline in PBMC and plasma
      viral loads.

PMID- 29599760
TI  - Characterization of Tail Sheath Protein of N4-Like Phage phiAxp-3.
AB  - Achromobacter phage phiAxp-3, an N4-like bacteriophage, specifically recognize
      Achromobacter xylosoxidans lipopolysaccharide (LPS) as its receptor. PhiAxp-3
      tail sheath protein (TSP, ORF69) shares 54% amino acid sequence identity with the
      TSP of phage N4 (gp65); the latter functions as a receptor binding protein and
      interacts with the outer membrane receptor NfrA of its host bacterium. Thus, we
      hypothesized that ORF69 is the receptor-binding protein of phiAxp-3. In the
      present study, a series of ORF69 truncation variants was constructed to identify
      the part(s) of this protein essential for binding to A. xylosoxidans LPS. Phage
      adsorption and enzyme-linked immunosorbent assay showed that amino acids 795-1195
      of the TSP, i.e., ORF69(795-1195), are sufficient and essential for receptor and
      binding. The optimum temperature and pH for the functions of ORF69 and ORF69(795
      1195) are 4/25 degrees C and 7, respectively. In vitro cytotoxicity assays showed
      that ORF69 and ORF69(795-1195) were respectively toxic and non-toxic to a human
      immortalized normal hepatocyte cell line (LO2; doses: 0.375-12 MUg). The
      potential of this non-toxic truncated version of phiASP-3 TSP for clinical
      applications is discussed.

PMID- 29599761
TI  - Evaluation of the Efficacy and Cross-Protective Immunity of Live-Attenuated
      Chimeric PCV1-2b Vaccine Against PCV2b and PCV2d Subtype Challenge in Pigs.
AB  - Porcine circovirus type 2 (PCV2) commercial vaccines are either inactivated PCV2
      isolates or subunit vaccine based on the Cap protein of PCV2. Currently, no live
      attenuated vaccines are yet available. Although the predominant circulating
      subtype worldwide is PCV2b, the emerging PCV2d subtype is also increasingly
      associated with PCV disease. In this study, piglets were inoculated with a live
      attenuated chimeric PCV1-2b vaccine before challenged with PCV2b and PCV2d
      isolates. Thirty-two piglets were randomly divided into seven groups: negative
      (sham-vaccinated, sham-challenged), VAC+PCV2b (PCV1-2b vaccinated, PCV2b
      challenged), VAC+PCV2d (PCV1-2b vaccinated, PCV2d-challenged), CHAL+PCV2b (sham
      vaccinated, PCV2b-challenged), CHAL+PCV2d (sham-vaccinated, PCV2d-challenged),
      CV+PCV2b (commercial-vaccinated, PCV2b-challenged), and CV+PCV2d (commercial
      vaccinated, PCV2d-challenged). The results showed that vaccinated challenged
      groups demonstrated high levels of anti-PCV2 antibody and reduced PCV2b and PCV2d
      loads both in serum and nasal swabs compared with the challenge-only groups. PCV2
      DNA was detected in the superficial inguinal lymph nodes of only one pig in each
      of the VAC+PCV2b and VAC+PCV2d groups (group mean values, 101.81 and 101.77
      genomic copies/g, respectively), which was significantly lower than those in
      CHAL+PCV2b and CHAL+PCV2d animals (group mean values, 1011.65 and 1010.60 genomic
      copies/g, respectively; P < 0.01). In addition, PCV2 DNA in each of the VAC+PCV2b
      and VAC+PCV2d groups was significantly lower than those in CV+PCV2b and CV+PCV2d
      animals (group mean values, 108.47 and 108.34 genomic copies/g, respectively; P <
      0.01), indicating that the live-attenuated PCV1-2b vaccine was more effective
      than commercial vaccine. The live-attenuated PCV1-2b vaccine was effective in
      reducing PCV2b/PCV2d viremia, shedding, and tissue viral loads in vaccinated
      challenged pigs compared with challenge-only piglets, indicating that the PCV1-2b
      prototype vaccine is a good candidate for a live-attenuated vaccine against both
      PCV2b and PCV2d subtypes. And we first revealed that the live-attenuated PCV1-2b
      vaccine could protect piglets from challenge with either PCV2b or PCV2d
      equivalently.

PMID- 29599762
TI  - PHB Biosynthesis Counteracts Redox Stress in Herbaspirillum seropedicae.
AB  - The ability of bacteria to produce polyhydroxyalkanoates such as poly(3
      hydroxybutyrate) (PHB) enables provision of a carbon storage molecule that can be
      mobilized under demanding physiological conditions. However, the precise function
      of PHB in cellular metabolism has not been clearly defined. In order to determine
      the impact of PHB production on global physiology, we have characterized the
      properties of a DeltaphaC1 mutant strain of the diazotrophic bacterium
      Herbaspirillum seropedicae. The absence of PHB in the mutant strain not only
      perturbs redox balance and increases oxidative stress, but also influences the
      activity of the redox-sensing Fnr transcription regulators, resulting in
      significant changes in expression of the cytochrome c-branch of the electron
      transport chain. The synthesis of PHB is itself dependent on the Fnr1 and Fnr3
      proteins resulting in a cyclic dependency that couples synthesis of PHB with
      redox regulation. Transcriptional profiling of the DeltaphaC1 mutant reveals that
      the loss of PHB synthesis affects the expression of many genes, including
      approximately 30% of the Fnr regulon.

PMID- 29599763
TI  - Streptococcus suis - The "Two Faces" of a Pathobiont in the Porcine Respiratory
      Tract.
AB  - Streptococcus (S.) suis is a frequent early colonizer of the upper respiratory
      tract of pigs. In fact, it is difficult to find S. suis-free animals under
      natural conditions, showing the successful adaptation of this pathogen to its
      porcine reservoir host. On the other hand, S. suis can cause life-threatening
      diseases and represents the most important bacterial cause of meningitis in pigs
      worldwide. Notably, S. suis can also cause zoonotic infections, such as
      meningitis, septicemia, endocarditis, and other diseases in humans. In Asia, it
      is classified as an emerging zoonotic pathogen and currently considered as one of
      the most important causes of bacterial meningitis in adults. The "two faces" of
      S. suis, one of a colonizing microbe and the other of a highly invasive pathogen,
      have raised many questions concerning the interpretation of diagnostic detection
      and the definition of virulence. Thus, one major research challenge is the
      identification of virulence-markers which allow differentiation of commensal and
      virulent strains. This is complicated by the high phenotypic and genotypic
      diversity of S. suis, as reflected by the occurrence of (at least) 33 capsular
      serotypes. In this review, we present current knowledge in the context of S. suis
      as a highly diverse pathobiont in the porcine respiratory tract that can exploit
      disrupted host homeostasis to flourish and promote inflammatory processes and
      invasive diseases in pigs and humans.

PMID- 29599764
TI  - A Dual Role for the Bacillus anthracis Master Virulence Regulator AtxA: Control
      of Sporulation and Anthrax Toxin Production.
AB  - Bacillus anthracis is an endemic soil bacterium that exhibits two different
      lifestyles. In the soil environment, B. anthracis undergoes a cycle of
      saprophytic growth, sporulation, and germination. In mammalian hosts, the
      pathogenic lifestyle of B. anthracis is spore germination followed by vegetative
      cell replication, but cells do not sporulate. During infection, and in specific
      culture conditions, transcription of the structural genes for the anthrax toxin
      proteins and the biosynthetic operon for capsule synthesis is positively
      controlled by the regulatory protein AtxA. A critical role for the atxA gene in
      B. anthracis virulence has been established. Here we report an inverse
      relationship between toxin production and sporulation that is linked to AtxA
      levels. During culture in conditions favoring sporulation, B. anthracis produces
      little to no AtxA. When B. anthracis is cultured in conditions favoring toxin
      gene expression, AtxA is expressed at relatively high levels and sporulation rate
      and efficiency are reduced. We found that a mutation within the atxA promoter
      region resulting in AtxA over-expression leads to a marked sporulation defect.
      The sporulation phenotype of the mutant is dependent upon pXO2-0075, an atxA
      regulated open reading frame located on virulence plasmid pXO2. The predicted
      amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain
      of sporulation sensor histidine kinases. It was shown previously that pXO2-0075
      overexpression suppresses sporulation. We have designated pXO2-0075 "skiA" for
      "sporulation kinase inhibitor." Our results indicate that in addition to serving
      as a positive regulator of virulence gene expression, AtxA modulates B. anthracis
      development.

PMID- 29599765
TI  - Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-delta Syndrome.
AB  - The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is important for multiple
      stages of herpesvirus replication including virus entry, replication, latency,
      and reactivation. Recently, patients with gain-of-function mutations in the
      p110delta-catalytic subunit of PI3K or in the p85-regulatory subunit of PI3K have
      been reported. These patients have constitutively active PI3K with
      hyperactivation of Akt. They present with lymphoproliferation and often have
      infections, particularly recurrent respiratory infections and/or severe virus
      infections. The most frequent virus infections are due to Epstein-Barr virus
      (EBV) and cytomegalovirus (CMV); patients often present with persistent EBV
      and/or CMV viremia, EBV lymphoproliferative disease, or CMV lymphadenitis. No
      patients have been reported with CMV pneumonia, colitis, or retinitis. Other
      herpesvirus infections have included herpes simplex pneumonia, recurrent zoster,
      and varicella after vaccination with the varicella vaccine. Additional viral
      infections have included adenovirus viremia, severe warts, and extensive
      Molluscum contagiosum virus infection. The increased susceptibility to virus
      infections in these patients is likely due to a reduced number of long-lived
      memory CD8 T cells and an increased number of terminally differentiated effector
      CD8 T cells.

PMID- 29599766
TI  - Room Temperature Stable PspA-Based Nanovaccine Induces Protective Immunity.
AB  - Streptococcus pneumoniae is a major causative agent of pneumonia, a debilitating
      disease particularly in young and elderly populations, and is the leading
      worldwide cause of death in children under the age of five. While there are
      existing vaccines against S. pneumoniae, none are protective across all
      serotypes. Pneumococcal surface protein A (PspA), a key virulence factor of S.
      pneumoniae, is an antigen that may be incorporated into future vaccines to
      address the immunological challenges presented by the diversity of capsular
      antigens. PspA has been shown to be immunogenic and capable of initiating a
      humoral immune response that is reactive across approximately 94% of pneumococcal
      strains. Biodegradable polyanhydrides have been studied as a nanoparticle-based
      vaccine (i.e., nanovaccine) platform to stabilize labile proteins, to provide
      adjuvanticity, and enhance patient compliance by providing protective immunity in
      a single dose. In this study, we designed a room temperature stable PspA-based
      polyanhydride nanovaccine that eliminated the need for a free protein component
      (i.e., 100% encapsulated within the nanoparticles). Mice were immunized once with
      the lead nanovaccine and upon challenge, presented significantly higher survival
      rates than animals immunized with soluble protein alone, even with a 25-fold
      reduction in protein dose. This lead nanovaccine formulation performed similarly
      to protein adjuvanted with Alum, however, with much less tissue reactogenicity at
      the site of immunization. By eliminating the free PspA from the nanovaccine
      formulation, the lead nanovaccine was efficacious after being stored dry for 60
      days at room temperature, breaking the need for maintaining the cold chain.
      Altogether, this study demonstrated that a single dose PspA-based nanovaccine
      against S. pneumoniae induced protective immunity and provided thermal stability
      when stored at room temperature for at least 60 days.

PMID- 29599767
TI  - Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial
      Cells and Their Effect on Antiviral Immunity.
AB  - The scientific community has reported several cases of microbes that exhibit
      elevated rates of antibiotic resistance in different regions of the planet. Due
      to this emergence of antimicrobial resistant microorganisms, the use of
      antibiotics as promoters of livestock animals' growth is being banned in most
      countries around the world. One of the challenges of agricultural immunology
      therefore is to find alternatives by modulating the immune system of animals in
      drug-independent safe food production systems. In this regard, in an effort to
      supplant antibiotics from bovine feeds, several alternatives were proposed
      including the use of immunomodulatory probiotics (immunobiotics). The purpose of
      this review is to provide an update of the status of the modulation of intestinal
      antiviral innate immunity of the bovine host by immunobiotics, and the beneficial
      impact of immunobiotics on viral infections, focused on intestinal epithelial
      cells (IECs). The results of our group, which demonstrate the capacity of
      immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered
      immune responses in bovine IECs and improve the resistance to viral infections,
      are highlighted. This review provides comprehensive information on the innate
      immune response of bovine IECs against virus, which can be further investigated
      for the development of strategies aimed to improve defenses in the bovine host.

PMID- 29599768
TI  - Mother's Milk: A Purposeful Contribution to the Development of the Infant
      Microbiota and Immunity.
AB  - Breast milk is the perfect nutrition for infants, a result of millions of years
      of evolution. In addition to providing a source of nutrition, breast milk
      contains a diverse array of microbiota and myriad biologically active components
      that are thought to guide the infant's developing mucosal immune system. It is
      believed that bacteria from the mother's intestine may translocate to breast milk
      and dynamically transfer to the infant. Such interplay between mother and her
      infant is a key to establishing a healthy infant intestinal microbiome. These
      intestinal bacteria protect against many respiratory and diarrheal illnesses, but
      are subject to environmental stresses such as antibiotic use. Orchestrating the
      development of the microbiota are the human milk oligosaccharides (HMOs), the
      synthesis of which are partially determined by the maternal genotype. HMOs are
      thought to play a role in preventing pathogenic bacterial adhesion though
      multiple mechanisms, while also providing nutrition for the microbiome.
      Extracellular vesicles (EVs), including exosomes, carry a diverse cargo,
      including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily
      detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs
      could therefore may play a further role in the development of the infant
      microbiome. This review considers the emerging role of breast milk microbiota,
      bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the
      consequent potential for modulation of neonatal immune system development.

PMID- 29599769
TI  - Trib1 Is Overexpressed in Systemic Lupus Erythematosus, While It Regulates
      Immunoglobulin Production in Murine B Cells.
AB  - Systemic lupus erythematosus (SLE) is a severe and heterogeneous autoimmune
      disease with a complex genetic etiology, characterized by the production of
      various pathogenic autoantibodies, which participate in end-organ damages. The
      majority of human SLE occurs in adults as a polygenic disease, and clinical
      flares interspersed with silent phases of various lengths characterize the usual
      evolution of the disease in time. Trying to understand the mechanism of the
      different phenotypic traits of the disease, and considering the central role of B
      cells in SLE, we previously performed a detailed wide analysis of gene expression
      variation in B cells from quiescent SLE patients. This analysis pointed out an
      overexpression of TRIB1. TRIB1 is a pseudokinase that has been implicated in the
      development of leukemia and also metabolic disorders. It is hypothesized that
      Trib1 plays an adapter or scaffold function in signaling pathways, notably in
      MAPK pathways. Therefore, we planned to understand the functional significance of
      TRIB1 overexpression in B cells in SLE. We produced a new knock-in model with B
      cell-specific overexpression of Trib1. We showed that overexpression of Trib1
      specifically in B cells does not impact B cell development nor induce any
      development of SLE symptoms in the mice. By contrast, Trib1 has a negative
      regulatory function on the production of immunoglobulins, notably IgG1, but also
      on the production of autoantibodies in an induced model. We observed a decrease
      of Erk activation in BCR-stimulated Trib1 overexpressing B cells. Finally, we
      searched for Trib1 partners in B cells by proteomic analysis in order to explore
      the regulatory function of Trib1 in B cells. Interestingly, we find an
      interaction between Trib1 and CD72, a negative regulator of B cells whose
      deficiency in mice leads to the development of autoimmunity. In conclusion, the
      overexpression of Trib1 could be one of the molecular pathways implicated in the
      negative regulation of B cells during SLE.

PMID- 29599771
TI  - Fresh Evidence for Platelets as Neuronal and Innate Immune Cells: Their Role in
      the Activation, Differentiation, and Deactivation of Th1, Th17, and Tregs during
      Tissue Inflammation.
AB  - Recent studies suggest that in addition to their common function in the
      regulation of thrombosis and hemostasis, platelets also contribute to tissue
      inflammation affecting adaptive immunity. Platelets have a number of pro
      inflammatory and regulatory mediators stored in their alpha-granules and dense
      granules, which are promptly released at sites of inflammation or tissue injury.
      Platelet-derived mediators include cytokines (IL-1alpha, IL-1beta, and TGFbeta1),
      chemokines (CXCL4 and CCL3), immunomodulatory neurotransmitters (serotonin,
      dopamine, epinephrine, histamine, and GABA), and other low-molecular-weight
      mediators. In addition, activated platelets synthesize a number of lipid pro
      inflammatory mediators such as platelet-activating factor and
      prostaglandins/thromboxanes. Notably, platelets express multiple toll-like
      receptors and MHC class I on their surface and store IgG in their alpha-granules.
      Platelet-derived factors are highly effective in directly or indirectly
      modulating the priming and effector function of various subsets of T cells.
      Besides secreting soluble factors, activated platelets upregulate a number of
      integrins, adhesion molecules, and lectins, leading to the formation of platelet
      T cells aggregates. Activated platelets are able to instantly release
      neurotransmitters acting similar to neuronal presynaptic terminals, affecting CD4
      T cells and other cells in close contact with them. The formation of platelet-T
      cell aggregates modulates the functions of T cells via direct cell-cell contact
      interactions and the local release of soluble factors including
      neurotransmitters. New data suggest an important role for platelets as neuronal
      and innate-like cells that directly recognize damage- or pathogen- associated
      molecular patterns and instantly communicate with T cells.

PMID- 29599772
TI  - The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast
      Growth Factor 23.
AB  - To determine the effect of the microbiota on vitamin D metabolism, serum 25
      hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25
      dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after
      conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D and
      were hypocalcemic. CN of the GF mice with microbiota, for 2 weeks recovered 25D,
      24,25D, and 1,25D levels. Females had more 25D and 24,25D than males both as GF
      mice and after CN. Introducing a limited number of commensals (eight commensals)
      increased 25D and 24,25D to the same extent as CN. Monocolonization with the
      enteric pathogen Citrobacter rodentium increased 25D and 24,25D, but the values
      only increased after 4 weeks of C. rodentium colonization when inflammation
      resolved. Fibroblast growth factor (FGF) 23 was extremely high in GF mice. CN
      resulted in an increase in TNF-alpha expression in the colon 2 days after CN that
      coincided with a reduction in FGF23 by 3 days that eventually normalized 25D,
      24,25D, 1,25D at 1-week post-CN and reinstated calcium homeostasis.
      Neutralization of FGF23 in GF mice raised 1,25D, without CN, demonstrating that
      the high FGF23 levels were responsible for the low calcium and 1,25D in GF mice.
      The microbiota induce inflammation in the GF mice that inhibits FGF23 to
      eventually reinstate homeostasis that includes increased 25D, 24,25D, and 1,25D
      levels. The microbiota through FGF23 regulates vitamin D metabolism.

PMID- 29599770
TI  - Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat
      Cancer.
AB  - Two decades of clinical cancer research with dendritic cell (DC)-based
      vaccination have proved that this type of personalized medicine is safe and has
      the capacity to improve survival, but monotherapy is unlikely to cure the cancer.
      Designed to empower the patient's antitumor immunity, huge research efforts are
      set to improve the efficacy of next-generation DC vaccines and to find
      synergistic combinations with existing cancer therapies. Immune checkpoint
      approaches, aiming to breach immune suppression and evasion to reinforce
      antitumor immunity, have been a revelation in the immunotherapy field. Early
      success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway
      has sparked the development of novel inhibitors and combination therapies. Hence,
      merging immunoregulatory tumor-specific DC strategies with PD-1-targeted
      approaches is a promising path to explore. In this review, we focus on the role
      of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting
      the full potential of DC therapy, different strategies to leverage DC
      immunopotency by impeding PD-1-mediated immune regulation are discussed,
      including the most advanced research on targeted therapeutic antibodies, lessons
      learned from chemotherapy-induced immune activation, and more recent developments
      with soluble molecules and gene-silencing techniques. An overview of DC/PD-1
      immunotherapy combinations that are currently under preclinical and clinical
      investigation substantiates the clinical potential of such combination
      strategies.

PMID- 29599773
TI  - Negative Regulation of Interferon-beta Production by Alternative Splicing of
      Tumor Necrosis Factor Receptor-Associated Factor 3 in Ducks.
AB  - Tumor necrosis factor receptor-associated factor 3 (TRAF3), an intracellular
      signal transducer, is identified as an important component of Toll-like receptors
      and RIG-I-like receptors induced type I interferon (IFN) signaling pathways.
      Previous studies have clarified TRAF3 function in mammals, but little is known
      about the role of TRAF3 in ducks. Here, we cloned and characterized the full
      length duck TRAF3 (duTRAF3) gene and an alternatively spliced isoform of duTRAF3
      (duTRAF3-S) lacking the fragment encoding amino acids 217-319, from duck embryo
      fibroblasts (DEFs). We found that duTRAF3 and duTRAF3-S played different roles in
      regulating IFN-beta production in DEFs. duTRAF3 through its TRAF domain
      interacted with duMAVS or duTRIF, leading to the production of IFN-beta. However,
      duTRAF3-S, containing the TRAF domain, was unable to bind duMAVS or duTRIF due to
      the intramolecular binding between the N- and C-terminal of duTRAF3-S that
      blocked the function of its TRAF domain. Further analysis identified that duTRAF3
      S competed with duTRAF3 itself for binding to duTRAF3, perturbing duTRAF3 self
      association, which impaired the assembly of duTRAF3-duMAVS/duTRIF complex,
      ultimately resulted in a reduced production of IFN-beta. These findings suggest
      that duTRAF3 is an important regulator of duck innate immune signaling and reveal
      a novel mechanism for the negative regulation of IFN-beta production via changing
      the formation of the homo-oligomerization of wild molecules, implying a novel
      regulatory role of truncated proteins.

PMID- 29599774
TI  - Chemokine CCL4 Induces Vascular Endothelial Growth Factor C Expression and
      Lymphangiogenesis by miR-195-3p in Oral Squamous Cell Carcinoma.
AB  - The inflammatory chemokine (C-C motif) ligand 4 (CCL4) plays an important role in
      the pathogenesis and progression of cancer. In particular, higher serum CCL4
      levels in patients with oral squamous cell carcinoma (OSCC) are associated with a
      more advanced stage of disease. OSCC accounts for approximately 95% of oral
      cancer in Taiwan and has a poor prognosis, due to aggressive local invasion and
      metastasis, leading to recurrence. OSCC spreads preferentially through lymphatic
      vessels and has the propensity to metastasize to the cervical lymph nodes even in
      the early stage of disease. Vascular endothelial growth factor C (VEGF-C) is an
      essential regulator of lymphangiogenesis. In particular, VEGF-C is specific to
      lymphatic vessel development, and VEGF-C expression levels have been found to
      directly correlate with lymph node metastasis in OSCC. However, it is unclear as
      to whether CCL4 correlates with VEGF-C expression and lymphangiogenesis in OSCC.
      We found that CCL4 increased VEGF-C expression and promoted lymphangiogenesis in
      oral cancer cells in vitro and in vivo. miR-195-3p mimic reversed CCL4-enhanced
      VEGF-C expression. CCL4 stimulation of oral cancer cells augmented JAK2 and STAT3
      phosphorylation. Thus, CCL4 may be a new molecular therapeutic target for
      inhibition of lymphangiogenesis and metastasis in OSCC.

PMID- 29599775
TI  - CD86 Expression by Monocytes Influences an Immunomodulatory Profile in
      Asymptomatic Patients with Chronic Chagas Disease.
AB  - In the chronic phase of Chagas disease, 60% of the patients develop the
      asymptomatic form known as indeterminate (IND). The remaining 30% of the patients
      develop a life-threatening form in which digestive and/or cardiac (CARD)
      alterations take place. The mechanisms underlying the development of severe forms
      of Chagas disease remain poorly understood. It is well known that interactions
      between immune cells such as monocytes and lymphocytes drive immune responses.
      Further, the co-stimulatory molecules CD80 and CD86 expressed by monocytes and
      subsets induce lymphocyte activation, thereby triggering cellular immune
      response. Here, we revealed, for the first time, the functional-phenotypic
      profile of monocytes subsets in Chagas disease. Using flow cytometry, we
      evaluated the effect of in vitro stimulation with Trypanosoma cruzi antigens on
      the expression of the co-stimulatory molecules CD80 and CD86 in different
      monocyte subsets of patients with IND and CARD clinical forms of Chagas disease.
      We also assessed the expression of toll-like receptor (TLR)-2, TLR-4, TLR-9, HLA
      DR, IL-10, and IL-12 in the monocyte subsets and of CTLA-4 and CD28, ligands of
      CD80 and CD86, in T lymphocytes. CD86 expression in all monocyte subsets was
      higher in IND patients when compared with non-infected (NI) individuals. After
      stimulation with T. cruzi, these patients also showed a higher frequency of
      CD4+CTLA-4+ T lymphocytes than NI individuals. We found an association between
      CD80 and CD28, and between CD86 and CTLA-4 expression, with a high frequency of
      regulatory T (Treg) cells in IND patients. We proposed that CD86 may be involved
      in immunoregulation by its association with CTLA-4 in asymptomatic patients. CD86
      and CTLA-4 interaction may influence Treg activation, and this could represent a
      new strategy to control inflammation and tissue damage.

PMID- 29599776
TI  - New Vaccine Formulations Containing a Modified Version of the Amastigote 2
      Antigen and the Non-Virulent Trypanosoma cruzi CL-14 Strain Are Highly Antigenic
      and Protective against Leishmania infantum Challenge.
AB  - Visceral leishmaniasis (VL) is a major public health issue reported as the second
      illness in mortality among all tropical diseases. Clinical trials have shown that
      protection against VL is associated with robust T cell responses, especially
      those producing IFN-gamma. The Leishmania amastigote 2 (A2) protein has been
      repeatedly described as immunogenic and protective against VL in different animal
      models; it is recognized by human T cells, and it is also commercially available
      in a vaccine formulation containing saponin against canine VL. Moving toward a
      more appropriate formulation for human vaccination, here, we tested a new
      optimized version of the recombinant protein (rA2), designed for Escherichia coli
      expression, in combination with adjuvants that have been approved for human use.
      Moreover, aiming at improving the cellular immune response triggered by rA2, we
      generated a recombinant live vaccine vector using Trypanosoma cruzi CL-14 non
      virulent strain, named CL-14 A2. Mice immunized with respective rA2, adsorbed in
      Alum/CpG B297, a TLR9 agonist recognized by mice and human homologs, or with the
      recombinant CL-14 A2 parasites through homologous prime-boost protocol, were
      evaluated for antigen-specific immune responses and protection against Leishmania
      infantum promastigote challenge. Immunization with the new rA2/Alum/CpG
      formulations and CL-14 A2 transgenic vectors elicited stronger cellular immune
      responses than control groups, as shown by increased levels of IFN-gamma,
      conferring protection against L. infantum challenge. Interestingly, the use of
      the wild-type CL-14 alone was enough to boost immunity and confer protection,
      confirming the previously reported immunogenic potential of this strain.
      Together, these results support the success of both the newly designed rA2
      antigen and the ability of T. cruzi CL-14 to induce strong T cell-mediated immune
      responses against VL in animal models when used as a live vaccine vector. In
      conclusion, the vaccination strategies explored here reveal promising
      alternatives for the development of new rA2 vaccine formulations to be translated
      human clinical trials.

PMID- 29599777
TI  - Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be
      Mitigated by C5aR2.
AB  - Bullous pemphigoid (BP), the most frequent autoimmune bullous disorder, is a
      paradigmatic autoantibody-mediated disease associated with autoantibodies against
      BP180 (type XVII collagen, Col17). Several animal models have been developed that
      reflect important clinical and immunological features of human BP. Complement
      activation has been described as a prerequisite for blister formation, however,
      the recent finding that skin lesions can be induced by anti-Col17 F(ab')2
      fragments indicates complement-independent mechanisms to contribute to blister
      formation in BP. Here, C5-/- mice injected with anti-Col17 IgG showed a reduction
      of skin lesions by about 50% associated with significantly less skin-infiltrating
      neutrophils compared to wild-type mice. Reduction of skin lesions and neutrophil
      infiltration was seen independently of the employed anti-Col17 IgG dose. Further,
      C5ar1-/- mice were protected from disease development, whereas the extent of skin
      lesions was increased in C5ar2-/- animals. Pharmacological inhibition of C5a
      receptor 1 (C5aR1) by PMX53 led to reduced disease activity when applied in a
      prophylactic setting. In contrast, PMX-53 treatment had no effect when first skin
      lesions had already developed. While C5aR1 was critically involved in neutrophil
      migration in vitro, its role for Col17-anti-Col17 IgG immune complex-mediated
      release of reactive oxygen species from neutrophils was less pronounced. Our data
      demonstrate that complement-dependent and -independent mechanisms coexist in anti
      Col17-autoantibody-mediated tissue destruction. C5aR1 and C5aR2 seem to play
      opposing roles in this process with C5aR1 exerting its primary effect in
      recruiting inflammatory cells to the skin during the early phase of the disease.
      Further studies are required to fully understand the role of C5aR2 in
      autoantibody-mediated skin inflammation.

PMID- 29599779
TI  - miR-301, Pleiotropic MicroRNA in Regulation of Inflammatory Bowel Disease and
      Colitis-Associated Cancer.

PMID- 29599780
TI  - Bi-Allelic Mutations in STXBP2 Reveal a Complementary Role for STXBP1 in
      Cytotoxic Lymphocyte Killing.
AB  - The ability of cytotoxic lymphocytes (CL) to eliminate virus-infected or
      cancerous target cells through the granule exocytosis death pathway is critical
      to immune homeostasis. Congenital loss of CL function due to bi-allelic mutations
      in PRF1, UNC13D, STX11, or STXBP2 leads to a potentially fatal immune
      dysregulation, familial haemophagocytic lymphohistiocytosis (FHL). This occurs
      due to the failure of CLs to release functional pore-forming protein perforin
      and, therefore, inability to kill the target cell. Bi-allelic mutations in
      partner proteins STXBP2 or STX11 impair CL cytotoxicity due to failed
      docking/fusion of cytotoxic secretory granules with the plasma membrane. One
      unique feature of STXBP2- and STX11-deficient patient CLs is that their short
      term in vitro treatment with a low concentration of IL-2 partially or completely
      restores natural killer (NK) cell degranulation and cytotoxicity, suggesting the
      existence of a secondary, yet unknown, pathway for secretory granule exocytosis.
      In the current report, we studied NK and T-cell function in an individual with
      late presentation of FHL due to hypomorphic bi-allelic mutations in STXBP2.
      Intriguingly, in addition to the expected alterations in the STXBP2 and STX11
      proteins, we also observed a concomitant significant reduction in the expression
      of homologous STXBP1 protein and its partner STX1, which had never been
      implicated in CL function. Further analysis of human NK and T cells demonstrated
      a functional role for the STXBP1/STX1 axis in NK and CD8+ T-cell cytotoxicity,
      where it appears to be responsible for as much as 50% of their cytotoxic
      activity. This discovery suggests a unique and previously unappreciated interplay
      between STXBP/Munc proteins regulating the same essential granule exocytosis
      pathway.

PMID- 29599778
TI  - Discovering Macrophage Functions Using In Vivo Optical Imaging Techniques.
AB  - Macrophages are an important component of host defense and inflammation and play
      a pivotal role in immune regulation, tissue remodeling, and metabolic regulation.
      Since macrophages are ubiquitous in human bodies and have versatile physiological
      functions, they are involved in virtually every disease, including cancer,
      diabetes, multiple sclerosis, and atherosclerosis. Molecular biological and
      histological methods have provided critical information on macrophage biology.
      However, many in vivo dynamic behaviors of macrophages are poorly understood and
      yet to be discovered. A better understanding of macrophage functions and dynamics
      in pathogenesis will open new opportunities for better diagnosis, prognostic
      assessment, and therapeutic intervention. In this article, we will review the
      advances in macrophage tracking and analysis with in vivo optical imaging in the
      context of different diseases. Moreover, this review will cover the challenges
      and solutions for optical imaging techniques during macrophage intravital
      imaging.

PMID- 29599781
TI  - Extracellular Vesicle Subtypes Released From Activated or Apoptotic T-Lymphocytes
      Carry a Specific and Stimulus-Dependent Protein Cargo.
AB  - Extracellular vesicles (EVs) are released from nearly all mammalian cells and
      different EV populations have been described. Microvesicles represent large EVs
      (LEVs) released from the cellular surface, while exosomes are small EVs (SEVs)
      released from an intracellular compartment. As it is likely that different
      stimuli promote the release of distinct EV populations, we analyzed EVs from
      human lymphocytes considering the respective release stimuli (activation Vs.
      apoptosis induction). We could clearly separate two EV populations, namely SEVs
      (average diameter <200 nm) and LEVs (diameter range between 200 and 1000 nm).
      Morphology and size were analyzed by electron microscopy and nanoparticle
      tracking analysis. Apoptosis induction caused a massive release of LEVs, while
      activated T-cells released SEVs and LEVs in considerably lower amounts. The
      release of SEVs from apoptotic T-cells was comparable with LEV release from
      activated ones. LEVs contained signaling proteins and proteins of the actin
      myosin cytoskeleton. SEVs carried cytoplasmic/endosomal proteins like the 70-kDa
      heat shock protein 70 (HSP70) or tumor susceptibility 101 (TSG101), microtubule
      associated proteins, and ubiquitinated proteins. The protein expression profile
      of SEVs and LEVs changed substantially after the induction of apoptosis. After
      apoptosis induction, HSP70 and TSG101 (often used as exosome markers) were highly
      expressed within LEVs. Interestingly, in contrast to HSP70 and TSG101, gelsolin
      and eps15 homology domain-containing protein 3 (EHD3) turned out to be specific
      for SEVs irrespective of the stimulus causing the EV release. Finally, we
      detected several subunits of the proteasome (PSMB9, PSMB10) as well as the danger
      signal HMGB1 exclusively within apoptotic cell-released LEVs. Thus, we were able
      to identify new marker proteins that can be useful to discriminate between
      distinct LEV subpopulations. The mass spectrometry proteomics data are available
      via ProteomeXchange with identifier PXD009074.

PMID- 29599782
TI  - C-Reactive Protein As a Mediator of Complement Activation and Inflammatory
      Signaling in Age-Related Macular Degeneration.
AB  - Age-related macular degeneration (AMD) is a devastating neurodegenerative disease
      affecting millions worldwide. Complement activation, inflammation, and the loss
      of choroidal endothelial cells have been established as key factors in both
      normal aging and AMD; however, the exact mechanisms for these events have yet to
      be fully uncovered. Herein, we provide evidence that the prototypic acute phase
      reactant, C-reactive protein (CRP), contributes to AMD pathogenesis. We discuss
      serum CRP levels as a risk factor for disease, immunolocalization of distinct
      forms of CRP in the at-risk and diseased retina, and direct effects of CRP on
      ocular tissue. Furthermore, we discuss the complement system as it relates to AMD
      pathophysiology, provide a model for the role of CRP in this disease, and outline
      current therapies being developed and tested to treat AMD patients.

PMID- 29599786
TI  - Coverage of Native Plants Is Key Factor Influencing the Invasibility of
      Freshwater Ecosystems by Exotic Plants in China.
AB  - Understanding the biotic and abiotic factors that influence the susceptibility of
      a community to invasion is beneficial for the prediction and management of
      invasive species and the conservation of native biodiversity. However, the
      relationships between factors and invasibility of a community have not been fully
      confirmed, and the factors most associated with the susceptibility of a community
      to invasion have rarely been identified. In this study, we investigated the
      species richness patterns in aquatic exotic and native plants and the
      relationships of exotic species richness with habitat and water environment
      factors in 262 aquatic plant communities in China. A total of 11 exotic plant
      species were recorded in our field survey, and we found neither a negative nor a
      positive relationship between aquatic exotic and native plant species richness.
      The aquatic exotic plant species richness is negatively correlated with the
      relative coverage and biomass of native plants but positively correlated with the
      total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD)
      concentrations in the water. The native plant species richness, native species'
      relative coverage, and native species' biomass were positively related to each
      other, whereas the TP, TN, and COD were also positively related to each other.
      The native plant species richness, native species' relative coverage, and native
      species biomass were each negatively correlated with the TP, TN, and COD. In
      addition, biotic rather than abiotic predictors accounted for most of the
      variation in exotic plant richness. Our results suggest that improving the
      vegetation coverage and the biodiversity of native plants is the most effective
      approach for preventing alien plant invasions and minimizing their impacts on
      freshwater ecosystems.

PMID- 29599784
TI  - Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3
      Kinase delta Syndrome: The European Society for Immunodeficiencies-Activated
      Phosphoinositide 3-Kinase delta Syndrome Registry.
AB  - Activated phosphoinositide 3-kinase (PI3K) delta Syndrome (APDS), caused by
      autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a
      heterogeneous primary immunodeficiency. While initial cohort-descriptions
      summarized the spectrum of clinical and immunological manifestations, questions
      about long-term disease evolution and response to therapy remain. The prospective
      European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize
      the disease course, identify outcome predictors, and evaluate treatment
      responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis
      of disease evolution in the first 68 patients pinpoints the early occurrence of
      recurrent respiratory infections followed by chronic lymphoproliferation,
      gastrointestinal manifestations, and cytopenias. Although most manifestations
      occur by age 15, adult-onset and asymptomatic courses were documented.
      Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan
      compared with 4/15 APDS2 patients. By age 20, half of the patients had received
      at least one immunosuppressant, but 2-3 lines of immunosuppressive therapy were
      not unusual before age 10. Response to rapamycin was rated by physician visual
      analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation
      showed the best response (8 complete, 11 partial, 6 no remission), while bowel
      inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2
      partial, 9 no remission) responded less well. Hence, non-lymphoproliferative
      manifestations should be a key target for novel therapies. This report from the
      ESID-APDS registry provides comprehensive baseline documentation for a growing
      cohort that will be followed prospectively to establish prognostic factors and
      identify patients for treatment studies.

PMID- 29599785
TI  - CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides.
AB  - NKT cells belong to a distinct subset of T cells that recognize hydrophobic
      antigens presented by major histocompatibility complex class I-like molecules,
      such as CD1d. Because NKT cells stimulated by antigens can activate or suppress
      other immunocompetent cells through an immediate production of a large amount of
      cytokines, they are regarded as immunological modulators. CD1d-restricted NKT
      cells are classified into two subsets, namely, type I and type II. CD1d
      restricted type I NKT cells express invariant T cell receptors (TCRs) and react
      with lipid antigens, including the marine sponge-derived glycolipid alpha
      galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize
      a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic
      peptides, by their diverse TCRs. In this review, we focus particularly on CD1d
      restricted type II NKT cells that recognize endogenous hydrophobic peptides
      presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I
      NKT cells usually act as pro-inflammatory cells but sometimes behave as anti
      inflammatory cells. It has been also demonstrated that CD1d-restricted type II
      NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they
      function as anti-inflammatory or pro-inflammatory cells depending on the
      situation. In line with this, CD1d-restricted type II NKT cells that recognize
      type II collagen peptide have been demonstrated to act as anti-inflammatory cells
      in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d
      restricted type II NKT cells reactive with sterol carrier protein 2 peptide have
      been demonstrated to be involved in the development of small vessel vasculitis in
      rats.

PMID- 29599787
TI  - Yield Potential of Sugar Beet - Have We Hit the Ceiling?
AB  - The yield of sugar beet has continuously increased in the past decades. The
      question arises, whether this progress will continue in the future. A key factor
      for increasing yield potential of the crop is breeding progress. It was related
      to a shift in assimilate partitioning in the plant toward more storage
      carbohydrates (sucrose), whereas structural carbohydrates (leaves, cell wall
      compounds) unintendedly declined. The yield potential of sugar beet was estimated
      at 24 t sugar ha-1. For maximum yield, sufficient growth factors have to be
      available and the crop has to be able to fully utilize them. In sugar beet,
      limitations result from the lacking coincidence of maximum irradiation rates and
      full canopy cover, sink strength for carbon assimilation and high water demand,
      which cannot be met by rainfall alone. After harvest, sugar losses during storage
      occur. The paper discusses options for a further increase in yield potential,
      like autumn sowing of sugar beet, increasing sink strength and related
      constraints. It is prospected that yield increase by further widening the ratio
      of storage and structural carbohydrates will come to its natural limit as a
      certain cell wall stability is necessary. New challenges caused by climate change
      and by prolonged processing campaigns will occur. Thus breeding for improved
      pathogen resistance and storage properties will be even more important for
      successful sugar beet production than a further increase in yield potential
      itself.

PMID- 29599783
TI  - Metabolic Adaptations of CD4+ T Cells in Inflammatory Disease.
AB  - A controlled and self-limiting inflammatory reaction generally results in removal
      of the injurious agent and repair of the damaged tissue. However, in chronic
      inflammation, immune responses become dysregulated and prolonged, leading to
      tissue destruction. The role of metabolic reprogramming in orchestrating
      appropriate immune responses has gained increasing attention in recent years.
      Proliferation and differentiation of the T cell subsets that are needed to
      address homeostatic imbalance is accompanied by a series of metabolic
      adaptations, as T cells traveling from nutrient-rich secondary lymphoid tissues
      to sites of inflammation experience a dramatic shift in microenvironment
      conditions. How T cells integrate information about the local environment, such
      as nutrient availability or oxygen levels, and transfer these signals to
      functional pathways remains to be fully understood. In this review, we discuss
      how distinct subsets of CD4+ T cells metabolically adapt to the conditions of
      inflammation and whether these insights may pave the way to new treatments for
      human inflammatory diseases.

PMID- 29599788
TI  - Viruses and Phytoparasitic Nematodes of Cicer arietinum L.: Biotechnological
      Approaches in Interaction Studies and for Sustainable Control.
AB  - Cicer arietinum L. (chickpea) is the world's fourth most widely grown pulse.
      Chickpea seeds are a primary source of dietary protein for humans, and chickpea
      cultivation contributes to biological nitrogen fixation in the soil, given its
      symbiotic relationship with rhizobia. Therefore, chickpea cultivation plays a
      pivotal role in innovative sustainable models of agro-ecosystems inserted in crop
      rotation in arid and semi-arid environments for soil improvement and the
      reduction of chemical inputs. Indeed, the arid and semi-arid tropical zones of
      Africa and Asia have been primary areas of cultivation and diversification. Yet,
      nowadays, chickpea is gaining prominence in Canada, Australia, and South America
      where it constitutes a main ingredient in vegetarian and vegan diets. Viruses and
      plant parasitic nematodes (PPNs) have been considered to be of minor and local
      impact in primary areas of cultivation. However, the introduction of chickpea in
      new environments exposes the crop to these biotic stresses, compromising its
      yields. The adoption of high-throughput genomic technologies, including genome
      and transcriptome sequencing projects by the chickpea research community, has
      provided major insights into genome evolution as well as genomic architecture and
      domestication. This review summarizes the major viruses and PPNs that affect
      chickpea cultivation worldwide. We also present an overview of the current state
      of chickpea genomics. Accordingly, we explore the opportunities that genomics,
      post-genomics and novel editing biotechnologies are offering in order to
      understand chickpea diseases and stress tolerance and to design innovative
      control strategies.

PMID- 29599789
TI  - Simultaneous Improvement and Genetic Dissection of Drought Tolerance Using
      Selected Breeding Populations of Rice.
AB  - Drought is the most important factor limiting rice yield in most rainfed areas of
      Asia and Africa. Four large BC2F2 populations consisted of 3,200 individuals,
      which were derived from crosses between an elite Geng variety, Jigeng88, and four
      donors from three different countries, were screened and progeny tested under
      severe drought stress, resulting in the development of 72 introgression lines
      (ILs) with significantly improved yield compared to the recurrent parent
      Jigeng88. These DT ILs plus four random populations (without drought selection
      population) from the same crosses were evaluated in replicated trials under both
      drought stress and non-stress conditions in two environments, and characterized
      with simple sequence repeat (SSR) markers to understand how directional selection
      was operating on the genetic variation of DT of rice. Thirteen DT QTLs of large
      effect were identified based on the significant allelic and genotypic frequency
      shits in the DT ILs by using the joint segregation distortion method. The 13 QTLs
      were validated by the genotypic differences at individual QTL in the random
      populations. Putative genetic networks consisting of 30 loci in 29 functional
      genetic units underlying DT were detected by X2 tests and non-random associations
      between or among DT loci in DT ILs from the four populations. Most large-effect
      DT QTLs were previously reported and located in the upstream of the genetic
      networks as putative regulators, and were either mapped to important regulatory
      genes for DT or drought responsiveness reported previously. In our study, five
      promising ILs with significantly improved yield were selected under both drought
      and normal irrigated conditions. The QTLs and their genetic networks underlying
      DT detected provided useful genetic information for further improving DT and
      yield using designed QTL pyramiding.

PMID- 29599790
TI  - An Updated Functional Annotation of Protein-Coding Genes in the Cucumber Genome.
AB  - Background: Although the cucumber reference genome and its annotation were
      published several years ago, the functional annotation of predicted genes,
      particularly protein-coding genes, still requires further improvement. In
      general, accurately determining orthologous relationships between genes allows
      for better and more robust functional assignments of predicted genes. As one of
      the most reliable strategies, the determination of collinearity information may
      facilitate reliable orthology inferences among genes from multiple related
      genomes. Currently, the identification of collinear segments has mainly been
      based on conservation of gene order and orientation. Over the course of plant
      genome evolution, various evolutionary events have disrupted or distorted the
      order of genes along chromosomes, making it difficult to use those genes as
      genome-wide markers for plant genome comparisons. Results: Using the localized
      LASTZ/MULTIZ analysis pipeline, we aligned 15 genomes, including cucumber and
      other related angiosperm plants, and identified a set of genomic segments that
      are short in length, stable in structure, uniform in distribution and highly
      conserved across all 15 plants. Compared with protein-coding genes, these
      conserved segments were more suitable for use as genomic markers for detecting
      collinear segments among distantly divergent plants. Guided by this set of
      identified collinear genomic segments, we inferred 94,486 orthologous protein
      coding gene pairs (OPPs) between cucumber and 14 other angiosperm species, which
      were used as proxies for transferring functional terms to cucumber genes from the
      annotations of the other 14 genomes. In total, 10,885 protein-coding genes were
      assigned Gene Ontology (GO) terms which was nearly 1,300 more than results
      collected in Uniprot-proteomic database. Our results showed that annotation
      accuracy would been improved compared with other existing approaches.
      Conclusions: In this study, we provided an alternative resource for the
      functional annotation of predicted cucumber protein-coding genes, which we expect
      will be beneficial for the cucumber's biological study, accessible from
      http://cmb.bnu.edu.cn/functional_annotation. Meanwhile, using the cucumber
      reference genome as a case study, we presented an efficient strategy for
      transferring gene functional information from previously well-characterized
      protein-coding genes in model species to newly sequenced or "non-model" plant
      species.

PMID- 29599792
TI  - Plant and Floret Growth at Distinct Developmental Stages During the Stem
      Elongation Phase in Wheat.
AB  - Floret development is critical for grain setting in wheat (Triticum aestivum),
      but more than 50% of grain yield potential (based on the maximum number of floret
      primordia) is lost during the stem elongation phase (SEP, from the terminal
      spikelet stage to anthesis). Dynamic plant (e.g., leaf area, plant height) and
      floret (e.g., anther and ovary size) growth and its connection with grain yield
      traits (e.g., grain number and width) are not clearly understood. In this study,
      for the first time, we dissected the SEP into seven stages to investigate plant
      (first experiment) and floret (second experiment) growth in greenhouse- and field
      grown wheat. In the first experiment, the values of various plant growth trait
      indices at different stages were generally consistent between field and
      greenhouse and were independent of the environment. However, at specific stages,
      some traits significantly differed between the two environments. In the second
      experiment, phenotypic and genotypic similarity analysis revealed that grain
      number and size corresponded closely to ovary size at anthesis, suggesting that
      ovary size is strongly associated with grain number and size. Moreover, principal
      component analysis (PCA) showed that the top six principal components PCs
      explained 99.13, 98.61, 98.41, 98.35, and 97.93% of the total phenotypic
      variation at the green anther, yellow anther, tipping, heading, and anthesis
      stages, respectively. The cumulative variance explained by the first PC decreased
      with floret growth, with the highest value detected at the green anther stage
      (88.8%) and the lowest at the anthesis (50.09%). Finally, ovary size at anthesis
      was greater in wheat accessions with early release years than in accessions with
      late release years, and anther/ovary size shared closer connections with grain
      number/size traits at the late vs. early stages of floral development. Our
      findings shed light on the dynamic changes in plant and floret growth-related
      traits in wheat and the effects of the environment on these traits.

PMID- 29599791
TI  - Prospecting for Microelement Function and Biosafety Assessment of Transgenic
      Cereal Plants.
AB  - Microelement contents and metabolism are vitally important for cereal plant
      growth and development as well as end-use properties. While minerals
      phytotoxicity harms plants, microelement deficiency also affects human health.
      Genetic engineering provides a promising way to solve these problems. As plants
      vary in abilities to uptake, transport, and accumulate minerals, and the key
      enzymes acting on that process is primarily presented in this review.
      Subsequently, microelement function and biosafety assessment of transgenic cereal
      plants have become a key issue to be addressed. Progress in genetic engineering
      of cereal plants has been made with the introduction of quality, high-yield, and
      resistant genes since the first transgenic rice, corn, and wheat were born in
      1988, 1990, and 1992, respectively. As the biosafety issue of transgenic cereal
      plants has now risen to be a top concern, many studies on transgenic biosafety
      have been carried out. Transgenic cereal biosafety issues mainly include two
      subjects, environmental friendliness and end-use safety. Different levels of gene
      confirmation, genomics, proteomics, metabolomics and nutritiomics, absorption,
      metabolism, and function have been investigated. Also, the different levels of
      microelement contents have been measured in transgenic plants. Based on the
      motivation of the requested biosafety, systematic designs, and analysis of
      transgenic cereal are also presented in this review paper.

PMID- 29599793
TI  - Utilization of a Wheat55K SNP Array for Mapping of Major QTL for Temporal
      Expression of the Tiller Number.
AB  - Maximum tiller number and productive tiller number are important traits for wheat
      grain yield, but research involving the temporal expression of tiller number at
      different quantitative trait loci (QTL) levels is limited. In the present study,
      a population set of 371 recombined inbred lines derived from a cross between
      Chuan-Nong18 and T1208 was used to construct a high-density genetic map using a
      Wheat55K SNP Array and to perform dynamic QTL analysis of the tiller number at
      four growth stages. A high-density genetic map containing 11,583 SNP markers and
      59 SSR markers that spanned 4,513.95 cM and was distributed across 21 wheat
      chromosomes was constructed. A total of 28 single environmental QTL were
      identified in the recombined inbred lines population, and among these, seven QTL
      were stable and used for multi-environmental and dynamic analysis. These QTL were
      mapped to chromosomes 2D, 4A, 4D, 5A, 5D, and 7D, respectively. Each QTL
      explained 1.63-21.22% of the observed phenotypic variation, with an additive
      effect from -20.51 to 11.59. Dynamic analysis showed that cqTN-2D.2 can be
      detected at four growth stages of tillering, explaining 4.92-17.16% of the
      observed phenotypic variations and spanning 13.71 Mb (AX-109283238-AX-110544009:
      82189047-95895626) according to the physical location of the flanking markers.
      The effects of the stable QTL were validated in the recombined inbred lines
      population, and the beneficial alleles could be utilized in future marker
      assisted selection. Several candidate genes for MTN and PTN were predicted. The
      results provide a better understanding of the QTL selectively expressing the
      control of tiller number and will facilitate future map-based cloning. 9.17% SNP
      markers showed best hits to the Chinese Spring contigs. It was indicated that
      Wheat55K Array was efficient and valid to construct a high-density wheat genetic
      map.

PMID- 29599794
TI  - Groundwater Depth Affects Phosphorus But Not Carbon and Nitrogen Concentrations
      of a Desert Phreatophyte in Northwest China.
AB  - Ecological stoichiometry is an important aspect in the analysis of the changes in
      ecological system composition, structure, and function and understanding of plant
      adaptation in habitats. Leaf carbon (C), nitrogen (N), and phosphorus (P)
      concentrations in desert phreatophytes can be affected by different depths of
      groundwater through its effect on the adsorption and utilization of nutrient and
      plant biomass. We examined the biomass, soil organic C, available (mineral) N,
      and available P, and leaf C, N, and P concentrations of Alhagi sparsifolia grown
      at varying groundwater depths of 2.5, 4.5, and 11.0 m in 2015 and 2016 growing
      seasons in a desert-oasis ecotone in northwest China. The biomass of A.
      sparsifolia and the C, N, and P concentrations in soil and A. sparsifolia showed
      different responses to various groundwater depths. The leaf P concentration of A.
      sparsifolia was lower at 4.5 m than at 2.5 and 11.0 m likely because of a biomass
      dilution effect. By contrast, leaf C and N concentrations were generally
      unaffected by groundwater depth, thereby confirming that C and N accumulations in
      A. sparsifolia were predominantly determined by C fixation through the
      photosynthesis and biological fixation of atmospheric N2, respectively. Soil C,
      N, and P concentrations at 4.5 m were significantly lower than those at 11.0 m.
      Leaf P concentration was significantly and positively correlated with soil N
      concentration at all of the groundwater depths. The C:N and C:P mass ratios of A.
      sparsifolia at 4.5 m were higher than those at the other groundwater depths,
      suggesting a defensive life history strategy. Conversely, A. sparsifolia likely
      adopted a competitive strategy at 2.5 and 11.0 m as indicated by the low C:N and
      C:P mass ratios. To our knowledge, this study is the first to elucidate the
      variation in the C, N, and P stoichiometry of a desert phreatophyte at different
      groundwater depths in an arid ecosystem.

PMID- 29599795
TI  - Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall
      Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana.
AB  - Transfer cells (TCs) play important roles in facilitating enhanced rates of
      nutrient transport at key apoplasmic/symplasmic junctions along the nutrient
      acquisition and transport pathways in plants. TCs achieve this capacity by
      developing elaborate wall ingrowth networks which serve to increase plasma
      membrane surface area thus increasing the cell's surface area-to-volume ratio to
      achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma
      (PP) cells of Arabidopsis leaf veins trans-differentiate to become PP TCs which
      likely function in a two-step phloem loading mechanism by facilitating unloading
      of photoassimilates into the apoplasm for subsequent energy-dependent uptake into
      the sieve element/companion cell (SE/CC) complex. We are using PP TCs in
      Arabidopsis as a genetic model to identify transcription factors involved in
      coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo
      Schiff propidium iodide-stained tissue revealed different profiles of temporal
      development of wall ingrowth deposition across maturing cotyledons and juvenile
      leaves, and a basipetal gradient of deposition across mature adult leaves. RNA
      Seq analysis was undertaken to identify differentially expressed genes common to
      these three different profiles of wall ingrowth deposition. This analysis
      identified 68 transcription factors up-regulated two-fold or more in at least two
      of the three experimental comparisons, with six of these transcription factors
      belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC
      genes using insertional mutants revealed significant reductions in levels of wall
      ingrowth deposition, particularly in a double mutant of NAC056 and NAC018, as
      well as compromised sucrose-dependent root growth, indicating impaired capacity
      for phloem loading. Collectively, these results support the proposition that
      Clade III members of the NAC-domain family in Arabidopsis play important roles in
      regulating wall ingrowth deposition in PP TCs.

PMID- 29599796
TI  - Altered Tuber Yield in Genetically Modified High-Amylose and Oil Potato Lines Is
      Associated With Changed Whole-Plant Nitrogen Economy.
AB  - Breeding for improved crop quality traits can affect non-target traits related to
      growth and resource use, and these effects may vary in different cultivation
      conditions (e. g., greenhouse vs. field). The objectives of this study are to
      investigate the growth and whole-plant nitrogen (N) economy of two genetically
      modified (GM) potato lines compared to their non-GM parental varieties and when
      grown in different cultivation conditions. A high-amylose GM potato line and its
      parent were grown under field and greenhouse conditions for one growing season in
      Sweden; and a GM oil potato line and its parent were grown in greenhouse
      conditions only. Tuber yield, above ground biomass, N uptake efficiency and other
      plant N economy traits were assessed. In both cultivation conditions, the GM
      lines produced between 1.5 and two times more tubers as compared with their
      parents. In the greenhouse, fresh tuber yield and N uptake efficiency were
      unaffected by the genetic modifications, but the GM-lines produced less tuber
      biomass per plant-internal N compared to their parents. In the field, the fresh
      tuber yield was 40% greater in the high-amylose line as compared with its parent;
      the greater fresh tuber yield in the high-amylose GM line was accomplished by
      higher water allocation to the harvested tubers, and associated with increased N
      recovery from soil (+20%), N uptake efficiency (+53%), tuber N content (+20%),
      and N accumulation (+120%) compared with the non-GM parent. The cultivation
      conditions influenced the yield and N economy. For example, the final fresh above
      ground plant biomass and N pool were considerably higher in the greenhouse
      conditions, whilst the tuber yield was higher in the field conditions. In
      conclusion, the genetic modification inducing high accumulation of amylose in
      potato tubers affected several non-target traits related to plant N economy, and
      increased the plant N uptake and accumulation efficiency of the field-grown
      plants. Due to strongly increased plant N accumulation compared to the parental
      variety, the cultivation of the high-amylose line is expected to require higher N
      fertilization rates. However, starch productivity per unit land area or soil N
      still is expected to be higher in the high-amylose line.

PMID- 29599797
TI  - Activation of ROP6 GTPase by Phosphatidylglycerol in Arabidopsis.
AB  - Plant Rho-like GTPases (ROPs) are switch-like proteins which play essential roles
      in controlling cell polarity development and cellular activities. ROPs are
      regulated by many factors, such as auxin, light, and RopGEFs and RopGAPs
      proteins. However, it has not been reported yet whether small molecules play a
      role in the regulation of ROP activity. Here, we showed that AtROP6 specially
      bound to a phospholipid, phosphatidylglycerol (PG), by the protein-lipid overlay
      and liposome sedimentation assays, and further MST assay gave a dissociation
      constant (Kd) of 4.8 +/- 0.4 MUM for binding of PG to His-AtROP6. PG profile
      analysis in Arabidopsis revealed that PG existed both in leaves and roots but
      with distinctive fatty acyl chain patterns. By evaluating AtROP6 activity using
      RIC1 effector binding-based assay, we found that PG stimulated AtROP6 activity.
      In the FM4-64 uptake experiment, PG inhibited AtROP6-mediated endocytosis
      process. By evaluating internalization of PIN2, PG was shown to regulate
      endocytosis process coordinately with NAA. Further root gravitropism experiment
      revealed that PG enhanced the AtROP6-mediated root gravity response. These
      results suggest that the phospholipid PG physically binds AtROP6, stimulates its
      activity and influences AtROP6-mediated root gravity response in Arabidopsis.

PMID- 29599798
TI  - SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly
      Accurate SNP Based Parentage Verification and Identification.
AB  - A major use of genetic data is parentage verification and identification as
      inaccurate pedigrees negatively affect genetic gain. Since 2012 the international
      standard for single nucleotide polymorphism (SNP) verification in Bos taurus
      cattle has been the ISAG SNP panels. While these ISAG panels provide an increased
      level of parentage accuracy over microsatellite markers (MS), they can validate
      the wrong parent at <=1% misconcordance rate levels, indicating that more SNP are
      needed if a more accurate pedigree is required. With rapidly increasing numbers
      of cattle being genotyped in Ireland that represent 61 B. taurus breeds from a
      wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred,
      and large to small herd size the Irish Cattle Breeding Federation (ICBF) analyzed
      different SNP densities to determine that at a minimum >=500 SNP are needed to
      consistently predict only one set of parents at a <=1% misconcordance rate. For
      parentage validation and prediction ICBF uses 800 SNP (ICBF800) selected based on
      SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele
      frequency (MAF) in the Irish cattle population. Large datasets require sample and
      SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF,
      parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We
      report here parentage, SNP QC, and a genomic sample QC pipelines to deal with the
      unique challenges of >1 million genotypes from a national herd such as SNP
      genotype errors from mis-tagging of animals, lab errors, farm errors, and
      multiple other issues that can arise. We divide the pipeline into two parts: a
      Genotype QC and an Animal QC pipeline. The Genotype QC identifies samples with
      low call rate, missing or mixed genotype classes (no BB genotype or ABTG alleles
      present), and low genotype frequencies. The Animal QC handles situations where
      the genotype might not belong to the listed individual by identifying: >1 non
      matching genotypes per animal, SNP duplicates, sex and breed prediction
      mismatches, parentage and progeny validation results, and other situations. The
      Animal QC pipeline make use of ICBF800 SNP set where appropriate to identify
      errors in a computationally efficient yet still highly accurate method.

PMID- 29599800
TI  - Application of Synthetic Polymeric Scaffolds in Breast Cancer 3D Tissue Cultures
      and Animal Tumor Models.
AB  - Preparation of three-dimensional (3D) porous scaffolds from synthetic polymers is
      a challenge to most laboratories conducting biomedical research. Here, we present
      a handy and cost-effective method to fabricate polymeric hydrogel and porous
      scaffolds using poly(lactic-co-glycolic) acid (PLGA) or polycaprolactone (PCL).
      Breast cancer cells grown on 3D polymeric scaffolds exhibited distinct survival,
      morphology, and proliferation compared to those on 2D polymeric surfaces. Mammary
      epithelial cells cultured on PLGA- or PCL-coated slides expressed extracellular
      matrix (ECM) proteins and their receptors. Estrogen receptor- (ER-) positive T47D
      breast cancer cells are less sensitive to 4-hydroxytamoxifen (4-HT) treatment
      when cultured on the 3D porous scaffolds than in 2D cultures. Finally, cancer
      cell-laden polymeric scaffolds support consistent tumor formation in animals and
      biomarker expression as seen in human native tumors. Our data suggest that the
      porous synthetic polymer scaffolds satisfy the basic requirements for 3D tissue
      cultures both in vitro and in vivo. The scaffolding technology has appealing
      potentials to be applied in anticancer drug screening for a better control of the
      progression of human cancers.

PMID- 29599799
TI  - Peroxisome Proliferator-Activated Receptor gamma and PGC-1alpha in Cancer: Dual
      Actions as Tumor Promoter and Suppressor.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is part of a nuclear
      receptor superfamily that regulates gene expression involved in cell
      differentiation, proliferation, immune/inflammation response, and lipid
      metabolism. PPARgamma coactivator-1alpha (PGC-1alpha), initially identified as a
      PPARgamma-interacting protein, is an important regulator of diverse metabolic
      pathways, such as oxidative metabolism and energy homeostasis. The role of PGC
      1alpha in diabetes, neurodegeneration, and cardiovascular disease is particularly
      well known. PGC-1alpha is also now known to play important roles in cancer,
      independent of the role of PPARgamma in cancer. Though many researchers have
      studied the expression and clinical implications of PPARgamma and PGC-1alpha in
      cancer, there are still many controversies about the role of PPARgamma and PGC
      1alpha in cancer. This review examines and summarizes some recent data on the
      role and action mechanisms of PPARgamma and PGC-1alpha in cancer, respectively,
      particularly the recent progress in understanding the role of PPARgamma in
      several cancers since our review was published in 2012.

PMID- 29599801
TI  - Continuous Flash Glucose Monitoring in children with Congenital Hyperinsulinism;
      first report on accuracy and patient experience.
AB  - Background: The factory calibrated FreeStyle Libre (FSL) flash glucose monitoring
      system has been recently introduced for use in patients with diabetes mellitus.
      There are no reports available regarding its use in patients with congenital
      hyperinsulinism (CHI). We have assessed the accuracy of FSL compared to the
      finger prick capillary blood glucose (CBG) over 2 weeks period in patients with
      CHI and evaluated the parents' experience of using FSL. Methods: Four hundred
      sixty-seven episodes of CBG along with corresponding swipe FSL readings were
      available from 11 children with CHI (0.5-5 years). A detailed questionnaire was
      completed by the parents. Results: The mean variation between the two methods was
      0.29 mmol/l (SD +/-1.07), higher readings by FSL compared to CBG. The FSL sensors
      stayed in-situ for an average period of 11.5 days. There was a positive
      correlation between the two methods (r = 0.7). The FSL tended to overestimate
      compared to CBG (bias = 0.29 mmol/l; 95% CI: 0.19 to 0.38). Only 70% of values
      were within the reference standard (+/-0.83 mmol/l) at glucose concentrations
      less than 5.6 mmol/l. The overall Mean Absolute Relative Difference (MARD) was
      17.9%. Forty two episodes of hypoglycaemia (CBG < 3.5 mmol/l) were noted but FSL
      identified only 52% of these episodes. The Bland Altman analysis showed the 95%
      limits of agreement between the two methods ranging from - 1.8 (95% CI: -1.97 to 
      1.64) to 2.37 (95% CI: 2.21 to 2.54). Majority of the parents found the glucose
      trend on FSL to be useful to detect and prevent hypoglycaemic episodes. All
      parents felt that FSL is a very easy and convenient method to measure the glucose
      especially during sleep. A significant proportion of parents felt that FSL
      readings were not accurate and 56% of parents expressed interest to continue
      using FSL after the trial period. Conclusion: Noticeable variability between the
      two methods of measuring the glucose was noted. Despite the ease of using the FSL
      system, concerns related to accuracy, especially at low glucose values do remain
      although parents find the glucose trend to be very useful. Further larger trials
      are needed in CHI patients before FSL is recommended as a routine alternative
      method for measuring glucose levels.

PMID- 29599802
TI  - Tuberculosis induced autoimmune haemolytic anaemia: a systematic review to find
      out common clinical presentations, investigation findings and the treatment
      options.
AB  - Background: Tuberculosis induced autoimmune haemolytic anaemia is a rare entity.
      The aim of this study was to explore its common presentations, investigation
      findings and treatment options through a systematic review of published reports.
      Methods: PubMed, Trip, Google Scholar, Science Direct, Cochrane Library, Open
      Grey, Grey literature report and the reference lists of the selected articles
      were searched for case reports in English on tuberculosis induced auto-immune
      haemolytic anaemia. PRISMA statement was used for systematic review. Quality
      assessment of the selected reports was done using the CARE guidelines. Results:
      Twenty-one articles out of 135 search results were included. Thirty-three percent
      of patients were reported from India. More than half had fever and pallor. The
      mean haemoglobin was 5.77 g/dl (SD 2.2). Positive direct coombs test was seen in
      all patients. Pulmonary tuberculosis (43%) was most prevalent. Twenty-nine
      percent of patients needed a combination of anti-tuberculosis medicines, blood
      transfusion and steroids. Higher percentage of disseminated TB induced AIHA (67%)
      needed steroids in comparison to the other types of TB induced AIHA (13%).
      Conclusions: Rarer complications of tuberculosis such as auto-immune haemolytic
      anaemia should be looked for especially in disease-endemic areas. Blood
      transfusion and steroids are additional treatment options along with the anti
      tuberculosis medicines.

PMID- 29599803
TI  - Neuroprotective Effects and Mechanism of beta-Asarone against Abeta1-42-Induced
      Injury in Astrocytes.
AB  - Emerging evidence suggests that activated astrocytes play important roles in AD,
      and beta-asarone, a major component of Acorus tatarinowii Schott, was shown to be
      a potential therapeutic candidate for AD. While our previous study found that
      beta-asarone could improve the cognitive function of rats hippocampally injected
      with Abeta, the effects of beta-asarone on astrocytes remain unclear, and this
      study aimed to investigate these effects. A rat model of Abeta1-42 (10 MUg) was
      established, and the rats were intragastrically treated with beta-asarone at
      doses of 10, 20, and 30 mg/kg or donepezil at a dose of 0.75 mg/kg. The sham and
      model groups were intragastrically injected with an equal volume of saline.
      Animals were sacrificed on the 28th day after administration of the drugs. In
      addition, a cellular model of Abeta1-42 (1.1 MUM, 6 h) was established, and cells
      were treated with beta-asarone at doses of 0, 2.06, 6.17, 18.5, 55.6, and 166.7
      MUg/mL. beta-Asarone improved cognitive impairment, alleviated Abeta deposition
      and hippocampal damage, and inhibited GFAP, AQP4, IL-1beta, and TNF-alpha
      expression. These results suggested that beta-asarone could alleviate the
      symptoms of AD by protecting astrocytes, possibly by inhibiting TNF-alpha and IL
      1beta secretion and then downregulating AQP4 expression.

PMID- 29599804
TI  - Metabolic Profiling Analysis of the Alleviation Effect of the Fractions of
      Niuhuang Jiedu Tablet on Realgar Induced Toxicity in Rats.
AB  - Niuhuang Jiedu Tablet (NJT) is a classical formula in treating acute tonsillitis,
      pharyngitis, and so on. In the formula, significant level of Realgar as a
      potentially toxic element is contained. Our previous experiments revealed that it
      was less toxic for combined Realgar in NJT. However, the active fraction of this
      prescription with toxicity alleviation effect on Realgar was still obscure. NJT
      was divided into five different polar fractions (NJT-PET, NJT-25, NJT-50, NJT-75,
      and NJT-95), and we explored the toxicity alleviation effect on Realgar. Based on
      1H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to
      identify different metabolic profiles. Liver and kidney histopathology
      examinations and serum clinical chemistry analysis were also performed. With
      pattern recognition analysis of metabolites in urine and serum, Realgar group
      showed a clear separation from control group, while the metabolic profiles of NJT
      PET, NJT-25, NJT-50, and NJT-95 groups were similar to Realgar group, and the
      metabolic profiles of NJT and NJT-75 groups were very close to control group.
      Statistics results were confirmed by the histopathological examination and
      biochemical assay. The present work indicated that 75% EtOH fraction of NJT was
      the most valid fraction with the toxicity alleviation effect on Realgar.

PMID- 29599805
TI  - Qi-Dong-Huo-Xue-Yin Inhibits Inflammation in Acute Lung Injury in Mice via Toll
      Like Receptor 4/Caveolin-1 Signaling.
AB  - Acute lung injury (ALI) is a critical illness with no current effective
      treatment. Caveolin-1 indirectly activates inflammation-associated signaling
      pathways by inhibiting endothelial nitric oxide synthase (eNOS). This induces an
      imbalance between pro- and anti-inflammatory cytokine levels, which are involved
      in the pathogenesis of ALI. The compound Chinese prescription Qi-Dong-Huo-Xue-Yin
      (QDHXY) is efficacious for ALI treatment via an anti-inflammatory effect;
      however, the exact underlying mechanism is unknown. Therefore, we explored the
      protective effect of QDHXY against lipopolysaccharide- (LPS-) induced ALI in
      mice. Histopathological changes in mouse lung tissues were studied. Furthermore,
      alterations in the serum levels of pro- and anti-inflammatory cytokines were
      investigated. The levels of tumor necrosis factor- (TNF-)alpha, interleukin- (IL
      ) 6, IL-1beta, and interferon-gamma-induced protein 10 in bronchoalveolar lavage
      fluid were measured. Additionally, the expression levels of myeloid
      differentiation factor 88 (MyD88), caveolin-1, and eNOS were assessed. QDHXY
      significantly reduced lung infiltration with inflammatory cells and the
      production of serum pro- and anti-inflammatory cytokines and inhibited the
      expression of TNF-alpha, IL-1beta, caveolin-1, and MyD88 but not eNOS. These
      indicate that QDHXY significantly improved the balance between pro- and anti
      inflammatory cytokine levels, possibly by inhibiting the caveolin-1 signaling
      pathway. Therefore, QDHXY may be a potential treatment for ALI.

PMID- 29599806
TI  - WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC
      beta3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral
      Neuropathy.
AB  - WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate
      clinical symptoms of diabetic peripheral neuropathy (DPN). This study
      investigated the gene and protein expression of the pain-related molecule PLC
      beta3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free
      male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78
      rats) groups, and the 78 model rats were used to establish the DPN model by
      intraperitoneal injection of streptozotocin and were then fed a high-fat diet for
      8 weeks. These rats were randomly divided into the model group, the high-, medium
      , and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin
      cream group, and the capsaicin cream + metformin group. After 4 weeks of
      continuous drug administration, the blood glucose, body weight, behavioral
      indexes, and sciatic nerve conduction velocity were measured. The pathological
      structure of the DRG and the sciatic nerve were observed. PLC-beta3 mRNA and
      protein levels in the DRG of rats were measured. Compared with the model group,
      the high-dose WTHX-Cream group showed increased sciatic nerve conduction
      velocity, improved sciatic nerve morphological changes, and increased expression
      of PLC-beta3 mRNA and protein in the DRG. This study showed that WTHX-Cream
      improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-beta3
      mRNA and protein expression in the diabetic DRG of DPN rats.

PMID- 29599807
TI  - Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract
      of Polyalthia suberosa Leaves.
AB  - In folk medicine, Polyalthia suberosa is used as abortifacient, laxative,
      febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for
      rheumatism and various skin infections. The present study was directed to
      evaluate the analgesic and anti-inflammatory activities of diethyl ether and n
      hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests
      including formalin-induced paw licking test, acetic acid induced writhing test,
      and tail immersion test were used to assess the analgesic activity. In addition,
      xylene-induced ear edema test was used to evaluate anti-inflammatory activity of
      PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as
      well as anti-inflammatory activities in mice. In formalin-induced paw licking
      test, acetic acid induced writhing test, and xylene-induced ear edema test, the
      extracts exhibited significant inhibition (*P < 0.05 versus control) of pain and
      inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed
      significant (*P < 0.05 versus control) latency at 30 min but another tested
      sample had no significant latency. From this study, it could be shown that
      Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents
      which support its use in traditional medicine.

PMID- 29599808
TI  - Evidence-Based Study to Compare Daodi Traditional Chinese Medicinal Material and
      Non-Daodi Traditional Chinese Medicinal Material.
AB  - Background: Daodi medicinal material is widely used in Chinese herb medication.
      However, there is a lack of systematic methodology for identifying
      characteristics associated with good quality and reliable efficacy of Daodi med
      material. Purpose: The purpose of this study is to provide some evidence to
      further substantiate the use of Daodi medicinal materials. Methods: Seven
      relevant databases were searched before July 2014. Two evaluators were
      responsible for screening and categorizing the results. The data was analyzed
      with Microsoft Excel 2007 and SPSS 21.0 statistical software. Results: Overall,
      107 articles were systematically analyzed. Of these studies, 55.1% (59/107)
      focused on the methodology to assess Daodi med-material, and 38.3% (41/107) were
      interested in med-material ingredients, soil physical and chemical properties,
      and the geological background system (GBS). Only 6.5% (7/107) of studies were
      mainly conducted as clinical trials and animal experiments. Conclusion:
      Comparisons between Daodi and non-Daodi materials have been studied mainly in
      terms of the ingredients or composition of medical materials, soil physics and
      chemistry, and the GBS, and some identifying methodologies have been created to
      identify Daodi attributes. Until now, there is still no consensus of comparison
      criteria between Daodi and non-Daodi medicinal material. Only a few studies were
      conducted through animal experiments and clinical trials to determine Daodi
      superiority.

PMID- 29599809
TI  - Electroacupuncture at ST36 Increases Bone Marrow-Derived Interstitial Cells of
      Cajal via the SDF-1/CXCR4 and mSCF/Kit-ETV1 Pathways in the Stomach of Diabetic
      Mice.
AB  - Background: The loss of interstitial cells of Cajal (ICC) is observed in diabetic
      gastroparesis. Electroacupuncture (EA) maintains ICC networks, but the effects
      and mechanisms of EA on ICC of bone marrow derivation in the stomach have not
      been investigated. Methods: C57BL/6 mice were randomized into six groups:
      control, diabetic (DM), bone marrow transplantation (BMT) + DM, BMT + DM + sham
      EA (SEA), BMT + DM + low-frequency EA (LEA), and BMT + DM + high-frequency (HEA).
      c-Kit+GFP+ cells in the stomach were detected by immunofluorescence staining.
      Western blotting and qRT-PCR were employed to determine c-Kit, GFP, SDF-1, CXCR4,
      mSCF, pERK, and ETV1 expression. Results: (1) c-Kit+GFP+ cells were elevated in
      the BMT + DM + LEA and HEA groups. (2) The mRNA and protein levels of GFP, SDF-1,
      and CXCR4 were increased in the BMT + DM + LEA and BMT + DM + HEA groups. (3) The
      mRNA and protein levels of mSCF, c-Kit, pERK, and ETV1 were significantly reduced
      in the DM group but markedly elevated in the BMT + DM + LEA and HEA groups.
      Conclusion: EA at ST36 increases bone marrow-derived ICC in the stomach of
      diabetic mice via the SDF-1/CXCR4 and mSCF/c-Kit-ETV1 pathways.

PMID- 29599810
TI  - The Aqueous Extract of Gynura divaricata (L.) DC. Improves Glucose and Lipid
      Metabolism and Ameliorates Type 2 Diabetes Mellitus.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by
      hyperglycemia and dyslipidemia caused by impaired insulin secretion and
      resistance of the peripheral tissues. A major pathogenesis of T2DM is obesity
      associated insulin resistance. Gynura divaricata (L.) DC. (GD) is a natural plant
      and has been reported to have numerous health-promoting effects on both animals
      and humans. In this study, we aimed to elucidate the regulatory mechanism of GD
      improving glucose and lipid metabolism in an obesity animal model induced by high
      fat and high-sugar diet in combination with low dose of streptozocin and an
      insulin-resistant HepG2 cell model induced by dexamethasone. The study showed
      that the water extract of GD (GD extract A) could significantly reduce fasting
      serum glucose, reverse dyslipidemia and pancreatic damage, and regulate the body
      weight of mice. We also found that GD extract A had low toxicity in vivo and in
      vitro. Furthermore, GD extract A may increase glucose consumption in insulin
      resistant HepG2 cells, markedly inhibit NF-kappaB activation, and decrease the
      impairment in signaling molecules of insulin pathway, such as IRS-1, AKT, and
      GLUT1. Overall, the results indicate that GD extract A is a promising candidate
      for the prevention and treatment of T2DM.

PMID- 29599811
TI  - The Pilot Survey of the Perception on the Practice Pattern, Diagnosis, and
      Treatment on Korean Medicine Insomnia: Focusing on the Difference between Korean
      Medical Neuropsychiatry Specialists and Korean Medical General Practitioners.
AB  - Introduction: This study aims to investigate the clinical practice states on the
      diagnosis and treatment for insomnia between Korean medical general practitioners
      (KMGPs) and Korean medical neuropsychiatry specialists (KMNPSs). Methods: We
      distributed questionnaires via email or in person to 1,017 KMGPs and via email to
      165 KMNPSs. We collected and analyzed responses from 305 (30.00%) KMGPs and 53
      (32.12%) KMNPSs. Results: Most KMGPs and KMNPSs responded that the number of new
      patients visiting the clinic for treatment of insomnia was less than 10 per month
      (78.2%). Frequently utilized therapies for insomnia are acupuncture and herbal
      decoctions. Particularly acupoint GV20 and Guipi decoction were chosen with the
      highest response rate. There was no difference between KMNPSs and KMGPs in the
      traditional Korean medical diagnosis methods. However, KMNPSs utilized more
      various methods to diagnose, treat, and evaluate insomnia and educated more
      actively sleep hygiene compared to KMGPs. Conclusions: This survey showed how
      insomnia is currently diagnosed and treated in Korean medical care settings.
      Moreover, we identified some differences between KMNPSs and KMGPs. Further
      research is required to explore the underlying reasons for these discrepancies
      among KMDs and to improve the quality of Korean medical clinical practice in
      treating insomnia.

PMID- 29599812
TI  - Study of Pharmacodynamic and Pharmacokinetic Interaction of Bojungikki-Tang with
      Aspirin in Healthy Subjects and Ischemic Stroke Patients.
AB  - Background: Bojungikki-tang (BJIKT) is a widely used traditional herbal formula
      in China, Japan, and Korea. There have been reports that several herbs among
      BJIKT have interactions with antiplatelet drugs, such as aspirin. This study
      aimed to assess whether BJIKT interacts with aspirin in terms of pharmacokinetics
      (PK) and pharmacodynamics (PD) in healthy subjects and ischemic stroke patients.
      Methods: The phase I interaction trial was a randomized, open-label, crossover
      study of 10 healthy male subjects, and the phase III interaction trial was a
      randomized, placebo-controlled, parallel study of 43 ischemic stroke patients.
      Each participant randomly received aspirin + BJIKT or aspirin + placebo. For PK
      analysis, plasma acetyl salicylic acid (ASA) and salicylic acid (SA) were
      evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2
      (TxB2) were measured. Results: In the PK parameters, mean area under curve,
      maximum concertation, and peak concentration time of ASA and SA were not
      different between two groups in healthy subjects and ischemic stroke patients. In
      the PD profiles, TxB2 concentrations and platelet aggregation were not affected
      by coadministration of BJIKT in healthy subjects and ischemic stroke patients.
      Conclusions: These results suggest that coadministration of BJIKT with aspirin
      may not result in herb-drug interaction.

PMID- 29599813
TI  - Cytopathologist-performed and ultrasound-guided fine needle aspiration cytology
      enhances diagnostic accuracy and avoids pitfalls: An overview of 20 years of
      personal experience with a selection of didactic cases.
AB  - Over the last few decades, fine needle aspiration cytology (FNA) has emerged as a
      SAFE (Simple, Accurate, Fast, Economical) diagnostic tool based on the
      morphologic evaluation of cells. The first and most important step in obtaining
      accurate results from FNA is to procure sufficient and representative material
      from the lesion and to appropriately transfer this material to the laboratory.
      Unfortunately, the most important aspect of this task occurs beyond the control
      of the cytopathologist, a key reason for obtaining unsatisfactory results with
      FNA. There is growing interest in the field of cytology in "cytopathologist
      performed ultrasound (US)-guided FNA," which has been reported to yield accurate
      results. The first author has been applying FNA in his own private cytopathology
      practice with a radiologist and under the guidance of US for more than 20 years.
      This study retrospectively reviews the utility of this practice. We present a
      selection of didactic examples under different headings that highlight the
      application of FNA by a cytopathologist, accompanied by US, under the guidance of
      a radiologist, in the form of an "outpatient FNA clinic." The use of this
      technique enhances diagnostic accuracy and prevents pitfalls. The highlights of
      each case are also outlined as "take-home messages."

PMID- 29599814
TI  - A mass protruding from the pancreas featuring extensive myxoid change.

PMID- 29599815
TI  - MowJoe: a method for automated-high throughput dissected leaf phenotyping.
AB  - Background: Accurate and automated phenotyping of leaf images is necessary for
      high throughput studies of leaf form like genome-wide association analysis and
      other forms of quantitative trait locus mapping. Dissected leaves (also referred
      to as compound) that are subdivided into individual units are an attractive
      system to study diversification of form. However, there are only few software
      tools for their automated analysis. Thus, high-throughput image processing
      algorithms are needed that can partition these leaves in their phenotypically
      relevant units and calculate morphological features based on these units.
      Results: We have developed MowJoe, an image processing algorithm that dissects a
      dissected leaf into leaflets, petiolule, rachis and petioles. It employs image
      skeletonization to convert leaves into graphs, and thereafter applies algorithms
      operating on graph structures. This partitioning of a leaf allows the derivation
      of morphological features such as leaf size, or eccentricity of leaflets.
      Furthermore, MowJoe automatically places landmarks onto the terminal leaflet that
      can be used for further leaf shape analysis. It generates specific output files
      that can directly be imported into downstream shape analysis tools. We applied
      the algorithm to two accessions of Cardamine hirsuta and show that our features
      are able to robustly discriminate between these accessions. Conclusion: MowJoe is
      a tool for the semi-automated, quantitative high throughput shape analysis of
      dissected leaf images. It provides the statistical power for the detection of the
      genetic basis of quantitative morphological variations.

PMID- 29599816
TI  - Treating patients in a trauma room equipped with computed tomography and
      patients' mortality: a non-controlled comparison study.
AB  - Background: To improve acute trauma care workflow, the number of trauma centers
      equipped with a computed tomography (CT) machine in the trauma resuscitation room
      has increased. The effect of the presence of a CT machine in the trauma room on a
      patient's outcome is still unclear. This study evaluated the association between
      a CT machine in the trauma room and a patient's outcome. Methods: Our study
      included all trauma patients admitted to a trauma center in Yokohama, Japan,
      between April 2014 and March 2016. We compared 140 patients treated using a
      conventional resuscitation room with 106 patients treated in new trauma rooms
      equipped with a CT machine. Results: For the group treated in a trauma room with
      a CT machine, the Injury Severity Score (13.0 vs. 9.0; p = 0.002), CT scans of
      the head (78.3 vs. 66.4%; p = 0.046), CT scans of the body trunk (75.5 vs. 58.6%;
      p = 0.007), intubation in the emergency department (48.1 vs. 30.7%; p = 0.008),
      and multiple trauma patients (47.2 vs. 30.0%; p = 0.008) were significantly
      higher and Trauma and Injury Severity Score probability of survival (96.75 vs.
      97.80; p = 0.009) was significantly lower than the group treated in a
      conventional resuscitation room. In multivariate analysis and propensity score
      matched analysis, being treated in a trauma room with a CT machine was an
      independent predictor for fewer hospital deaths (odds ratio 0.002; 95% CI 0.00
      0.75; p = 0.04, and 0.07; 0.00-0.98, respectively). Conclusions: Equipping a
      trauma room with a CT machine reduced the time in decision-making for treating a
      trauma patient and subsequently lowered the mortality of trauma patients.

PMID- 29599817
TI  - Wenyang Huazhuo Tongluo formula inhibits fibrosis via suppressing Wnt/beta
      catenin signaling pathway in a Bleomycin-induced systemic sclerosis mouse model.
AB  - Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by
      fibrosis of the skin and internal organs. So far, no Western medicine treatment
      can completely inhibit or reverse the progress of SSc, while at the same time,
      our previous series of studies have shown that the treatment of SSc by the
      Wenyang Huazhuo Tongluo formula (WYHZTL), a Chinese herbal decoction, shows a
      delightful prospect. The aim of this study is to further investigate the
      mechanism of anti-fibrosis of WYHZTL formula in SSc mouse model. Methods: The
      Bleomycin-induced SSc mouse model was treated with saline (BLM), high-dosage of
      WYHZTL formula (WYHZTL-H), medium-dosage of WYHZTL formula (WYHZTL-M), low-dosage
      of WYHZTL formula (WYHZTL-L) and XAV-939, a small molecule inhibitor of Wnt/beta
      catenin signaling pathway, by the intragastric administration and intraperitoneal
      injection, respectively. The mRNA and protein levels of Wnt/beta-catenin
      signaling pathway associated genes, fibrosis markers and histopathology were
      detected by reverse transcription-quantitative polymerase chain reaction, Western
      blotting and hematoxylin/eosin-staining. The levels of Wnt1, CTGF and DKK1
      protein in serum were detected by enzyme-linked immunosorbent assay. Results:
      Compared with BLM group, the WYHZTL formula and XAV-939 could significantly
      inhibit the thickness of the skin tissue of the SSc mouse model. The mRNA
      expression levels of GSK3beta and DKK1 in the WYHZTL formula and XAV-939-treated
      group were significantly higher than those in the BLM group, while Wnt1, beta
      catenin, TCF4, cyclin D1, survivin, VEGF, CTGF, FN1, collagen I/III were
      decreased. Compared with BLM group, the protein expression levels of GSK3beta and
      DKK1 in the WYHZTL formula and XAV-939-treated group were upregulated, while
      Wnt1, beta-catenin, cyclin D1, survivin, CTGF, FN1, collagen I/III were
      downregulated. WYHZTL formula and XAV-939 could inhibit expression of Wnt1 and
      CTGF, but promoted DKK1 in serum. Furthermore, WYHZTL-H seemed more effective
      than WYHZTL-M and/or XAV-939 on regulating Wnt1, beta-catenin, TCF4, GSK3beta,
      DKK1, cyclin D1, survivin, VEGF, CTGF, FN1 and collagen I/III. Conclusion: This
      present study demonstrates that WYHZTL formula has anti-fibrosis effect in
      Bleomycin-induced SSc mouse model in a dosage-dependent manner, and the molecular
      mechanism may be related to the inhibition of Wnt/beta-catenin signaling pathway.

PMID- 29599818
TI  - Cellular prognostic markers in hepatitis-related hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and
      accounts for about 6% of all new cancers diagnosed worldwide. Moreover, it is the
      third and the fifth leading cause of death from cancer in men and women,
      respectively. HBV and HCV chronic infection is the main risk factor for HCC. A
      range of therapies are used in the management of HCC according to the extent and
      severity of liver disease. In this perspective, evaluation of prognosis
      represents a crucial step for proper management of HCC patients. However, the
      clinical outcome can be significantly different in HCC patients within the same
      stage of disease. Therefore, many efforts have been made to define new parameters
      with more precise prognostic value, and the search for HCC prognostic markers is
      gaining momentum. The present review aims at providing an update on cellular
      prognostic markers for HCC.

PMID- 29599819
TI  - The new WHO decision-making framework on vaccine use in acute humanitarian
      emergencies: MSF experience in Minkaman, South Sudan.
AB  - Introduction: The main causes of death during population movements can be
      prevented by addressing the population's basic needs. In 2013, the World Health
      Organization (WHO) issued a framework for decision making to help prioritize
      vaccinations in acute humanitarian emergencies. This article describes MSF's
      experience of applying this framework in addition to addressing key population
      needs in a displacement setting in Minkaman, South Sudan. Case description:
      Military clashes broke out in South Sudan in December 2013. By May 2014,
      Minkaman, a village in the Lakes State, hosted some 85,000 displaced people. MSF
      arrived in Minkaman on 28 December 2013 and immediately provided interventions to
      address the key humanitarian needs (health care, access to drinking water,
      measles vaccination). The WHO framework was used to identify priority vaccines:
      those preventing outbreaks (measles, polio, oral cholera vaccine, and vaccine
      against meningococcal meningitis A (MenAfrivac(r))) and those reducing childhood
      morbidity and mortality (pentavalent vaccine that combines diphtheria, tetanus,
      whooping cough, hepatitis B, and Haemophilus influenzae type B; pneumococcal
      vaccine; and rotavirus vaccine). By mid-March, access to primary and secondary
      health care was ensured, including community health activities and the provision
      of safe water. Mass vaccination campaigns against measles, polio, cholera, and
      meningitis had been organized. Vaccination campaigns against the main deadly
      childhood diseases, however, were not in place owing to lack of authorization by
      the Ministry of Health (MoH). Conclusions: The first field use of the new WHO
      framework for prioritizing vaccines in acute emergencies is described. Although
      MSF was unable to implement the full package of priority vaccines because
      authorization could not be obtained from the MoH, a series of mass vaccination
      campaigns against key epidemic-prone diseases was successfully implemented within
      a complex emergency context. Together with covering the population's basic needs,
      this might have contributed to reducing mortality levels below the emergency
      threshold and to the absence of epidemics. For the WHO framework to be used to
      its full potential it must not only be adapted for field use but, most
      importantly, national decision makers should be briefed on the framework and its
      practical implementation.

PMID- 29599820
TI  - A structured approach to integrating mental health services into primary care:
      development of the Mental Health Scale Up Nigeria intervention (mhSUN).
AB  - Background: The treatment gap for mental illness in Nigeria, as in other sub
      Saharan countries, is estimated to be around 85%. There is need to prioritise
      mental health care in low and middle income countries by providing a strong body
      of evidence for effective services, particularly with a view to increasing
      international and government confidence in investment in scaling up appropriate
      services. This paper lays out the processes by which a programme to integrate
      evidence-based mental health care into primary care services in Nigeria was
      designed, including a research framework to provide evidence from a robust
      evaluation. Methods: This paper forms the first step in the overall process
      evaluation of the mhSUN intervention, where standard research practice indicates
      that the intervention, and its development, is clearly documented prior to
      subsequent evaluation. The report covers the period of programme development and
      evaluation design, and study site and design was chosen to allow generalisability
      and practical conclusions to be drawn for service development in Nigeria. In
      order to design an intervention that was informed by evidence and took into
      account local context and input of stakeholders, a structured process was
      followed, including: (1) Engagement of relevant stakeholders for information
      gathering and buy-in; (2) Literature review and gathering of pertinent evidence;
      (3) Situation analysis at a national and local level; (4) Model development
      (using Theory of Change); (5) Ongoing consultation, recognising the iterative
      nature of Theory of Change, and need for ongoing refinement of complex
      interventions. Results: The different sections of the structured approach
      resulted in outputs that built the necessary components (literature review,
      situation analysis) for informing the Theory of Change. A Theory of Change map is
      presented, which includes transparent documentation of the assumptions and logic
      behind the activities to drive the desired change. In addition, it documents the
      indicators necessary to measure fidelity and draw conclusions as to hypothesised
      effects of different mechanisms of action in subsequent evaluation. Conclusion:
      In addition to the details of ensuring robust evaluation design, there are a
      number of considerations that are particular to the context that must be taken
      into account in programme development, including the relationships between
      ultimate beneficiaries, implementers, host government and institutions, donors,
      and programme evaluators. Structured methods from existing frameworks can be
      drawn upon to use and collate relevant information to maximise the local
      applicability of a generic evidence base. Theory of Change, with its documented
      assumptions can form the basis of subsequent evaluation and iterative programme
      refinement, contributing to a more scientifically valid means of developing
      mental health programmes for scale up.

PMID- 29599821
TI  - Disposable microfluidic micromixers for effective capture of Cryptosporidium
      parvum oocysts from water samples.
AB  - Background: Protecting drinking water supplies from pathogens such as
      Cryptosporidium parvum is a major concern for water utilities worldwide. The
      sensitivity and specificity of current detection methods are largely determined
      by the effectiveness of the concentration and separation methods used. The
      purpose of this study is to develop micromixers able to specifically isolate and
      concentrate Cryptosporidium, while allowing in situ analysis. Results: In this
      study, disposable microfluidic micromixers were fabricated to effectively isolate
      Cryptosporidium parvum oocysts from water samples, while allowing direct
      observation and enabling quantification of oocysts captured in the device using
      high quality immunofluorescence microscopy. In parallel, quantitative analysis of
      the capture yield was carried out by analyzing the waste from the microfluidics
      outlet with an Imaging Flow Cytometer. At the optimal flow rate, capture
      efficiencies up to 96% were achieved in spiked samples. Conclusions: Scaled
      microfluidic isolation and detection of Cryptosporidium parvum will provide a
      faster and more efficient detection method for Cryptosporidium compared to other
      available laboratory-scale technologies.

PMID- 29599822
TI  - Novel phenotype of 5p13.3-q11.2 duplication resulting from supernumerary marker
      chromosome 5: implications for management and genetic counseling.
AB  - Background: Supernumerary marker chromosomes derived from chromosome 5 (SMC5) and
      5p13 duplication syndrome are rare disorders, and phenotypic descriptions of
      patients are necessary to better define genotype-phenotype correlations for
      accurate, comprehensive genetic counseling. The purpose of this study is to
      highlight the unique findings of a patient with a 5p13.3-q11.2 duplication
      arising from a SMC5 and compare and contrast the phenotype with cases in the
      literature. Case presentation: We report on an adult male with a 22 Mb
      duplication of chromosome 5p13.3-q11.2 resulting from a small SMC5. The patient
      has a history of prenatal polyhydramnios, dysmorphic features, respiratory
      issues, talipes equinovarus, hypotonia, developmental delay, and autistic
      features. The patient also has novel features of aortic dilation, pectus
      excavatum, kyphoscoliosis, and skin striae, suggestive of a connective tissue
      disorder. Despite these features he did not meet clinical diagnostic criteria for
      a well-characterized connective tissue disorder. Additional molecular genetic
      testing for syndromic and non-syndromic aortic aneurysms was negative.
      Conclusions: Many of the patient's features are consistent with individuals
      reported with 5p13 duplication syndrome and similar cases of SMC5, including
      polyhydramnios, macrocephaly, dolichocephaly, pre-auricular pits, arachnodactyly,
      respiratory problems, and developmental delays. It is unclear if the patient's
      unique features of aortic dilation, pectus excavatum, kyphoscoliosis, and skin
      striae could be novel features of the SMC5 given its rarity and the few well
      phenotyped adults in the literature. This report reviews the literature and
      provides additional phenotypic information to define the genotype-phenotype
      correlation of SMC5 and 5p13 duplication syndrome.

PMID- 29599824
TI  - Climate research must sharpen its view.
AB  - Human activity is changing Earth's climate. Now that this has been acknowledged
      and accepted in international negotiations, climate research needs to define its
      next frontiers.

PMID- 29599823
TI  - Regional differences in the prevalence of diabetic retinopathy: a multi center
      study in Brazil.
AB  - Background: Diabetic retinopathy has a significant impact in every healthcare
      system. Despite that fact, there are few accurate estimates in the prevalence of
      DR in Brazil's different geographic regions, particularly proliferative DR and
      diabetic macular edema. This study aims to determine the prevalence of diabetic
      retinopathy in Brazil's five continental regions and its determinant factors.
      Methods: This multi center, cross-sectional, observational study, conducted
      between August 2011 and December 2014, included patients with type 1 diabetes
      from the 5 Brazilian geographic regions (South, Southeast, North, Northeast and
      Midwest). During a clinical visit, a structured questionnaire was applied, blood
      sampling was collected and each patient underwent mydriatic binocular indirect
      ophthalmoscopy evaluation. Results: Data was obtained from 1644 patients, aged
      30.2 +/- 12 years (56.1% female, 54.4% Caucasian), with a diabetes duration of
      15.5 +/- 9.3 years. The prevalence of diabetic retinopathy was 242 (36.1%) in the
      Southeast, 102 (42.9%) in the South, 183 (29.9%) in the North and Northeast and
      54 (41.7%) in the Midwest. Multinomial regression showed no difference in the
      prevalence of non-proliferative diabetic retinopathy in each geographic region,
      although, prevalence of proliferative diabetic retinopathy (p = 0.022), and
      diabetic macular edema (p = 0.003) was higher in the Midwest. Stepwise analyses
      reviled duration of diabetes, level of HbA1c and hypertension as independent
      variables. Conclusions: The prevalence of non proliferative diabetic retinopathy
      in patients with type 1 diabetes was no different between each geographic region
      of Brazil. The Midwest presented higher prevalence of proliferative diabetic
      retinopathy and diabetic macular edema. Duration of DM and glycemic control is of
      central importance to all. Hypertension is another fundamental factor to every
      region, at special in the South and Southeast. Glycemic control and patients in
      social and economic vulnerability deserves special attention in the North and
      Northeast of Brazil.

PMID- 29599825
TI  - Case-control study on individual risk factors of carpal tunnel syndrome.
AB  - This study was conducted to observe the characteristics of the risk factors of
      carpal tunnel syndrome (CTS) in Chinese population. CTS of 1,512 outpatients aged
      41-70 years were without any other diseases which could cause numbness as a case
      group, and 4,536 non-CTS outpatients as a control group were involved in the
      study in 2013-2014. Both groups received a questionnaire and the case group
      received another electrical physiological examination. The results showed the
      odds ratio (OR) of age is 0.990 (95% CI, 0.984-0.996). The OR of BMI is 1.096
      (95% CI, 1.077-1.115). The OR of smoking is 4.862 (95% CI, 3.991-5.925). The OR
      of wrist injury is 1.313 (95% CI, 1.019-1.691). The OR of diabetes mellitus is
      1.837 (95% CI, 1.557-2.168). The OR of hypertension is 0.805 (95% CI, 0.688
      0.942). The OR of hypothyroidism is 1.385 (95% CI, 1.119-1.715). The OR of
      rheumatic disease is 4.450 (95% CI, 3.712-5.215). The results showed that sex,
      age, smoking, wrist injury, diabetes mellitus, hypothyroidism and wrist working
      are all risk factors of CTS. Hypertension could be a protection factor of CTS in
      early phase but will increase the risk in a long-term high blood pressure.
      Smoking, alcohol and diabetes mellitus can be predictors of moderate and severe
      CTS.

PMID- 29599826
TI  - Gas chromatography-time of flight/mass spectrometry-based metabonomics of changes
      in the urinary metabolic profile in osteoarthritic rats.
AB  - The aim of the present study was to explore changes in the urinary metabolic
      spectrum in rats with knee osteoarthritis, using gas chromatography-time of
      flight/mass spectrometry (GC-TOF/MS) to determine the metabonomic disease
      pathogenesis. Sprague-Dawley rats were randomly divided into the control and
      model groups (n=8/group), and 20 ul of 4% papain and 0.03 M L-cysteine was
      injected into the right knee on days 1, 3 and 7 to establish the knee
      osteoarthritis model. Following 14 days, urine was collected over 12 h and
      cartilage ultrastructural damage was assessed by hematoxylin-eosin staining. GC
      TOF/MS, combined with principal component analysis, partial least squares
      discriminant modeling and orthogonal partial least squares discriminant modeling,
      was used to analyze the changes in the metabolic spectrum trajectory and to
      identify potential biomarkers and their related metabolic pathways. Compared with
      the control group, the synovial cell lining of the knee joint exhibited
      proliferation, inflammatory cell infiltration and collagen fiber hyperplasia in
      the knee osteoarthritis group. A total of 23 potential biomarkers were
      identified, including alanine, alpha-ketoglutarate, asparagine, maltose and
      glutamine. Furthermore, metabolomic pathogenesis of osteoarthritis may be related
      to disorders of amino acid metabolism, energy metabolism, fatty acid metabolism,
      vitamin B6 metabolism and nucleic acid metabolism.

PMID- 29599827
TI  - Effects of sevoflurane pretreatment on the apoptosis of rat H9c2 cardiomyocytes
      and the expression of GRP78.
AB  - The protective effect of sevoflurane on apoptosis of rat H9c2 cardiomyocytes
      induced by H2O2 and the effect on the expression of glucose-regulated protein 78
      (GRP78) were investigated. H9c2 cells were routinely cultured and divided into
      the control, model and sevoflurane groups. Cells in the model group were treated
      with 400 uM H2O2, and cells in the sevoflurane group were pretreated with
      sevoflurane prior to treatment with 400 uM H2O2. MTT assay was used to assess
      cell viability. Annexin V-propidium iodide (AV-PI) double staining flow cytometry
      was used to detect apoptosis. The intracellular free Ca2+ concentration was
      measured by the fluorescence-based assay using Fluo-3 AM as a calcium ion
      fluorescence probe. The mRNA expression level of GRP78 and protein expression
      levels of GRP78, CHOP and caspase-12 were measured using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and western blot analysis,
      respectively. The assays showed that after sevoflurane pretreatment the H9c2 cell
      viability was significantly increased, whereas the H2O2-induced apoptosis,
      intracellular Ca2+ concentration, mRNA expression of GRP78, and the protein
      expression of GRP78, CHOP and caspase-12 were all reduced. The results show that
      pretreatment with sevoflurane inhibited H2O2-induced apoptosis in H9c2 cells. The
      mechanism may be related to inhibition of the stress-related protein GRP78
      expression in endoplasmic reticulum, resulting in decreased intracellular Ca2+
      concentration and the downregulation of CHOP and caspase-12 expression levels.

PMID- 29599828
TI  - Age-related changes of the spinal cord: A biomechanical study.
AB  - Although it is known that aging plays an important role in the incidence and
      progression of cervical spondylotic myelopathy (CSM), the underlying mechanism is
      unclear. Studies that used fresh bovine cervical spinal cord report the gray
      matter of the cervical spinal cord as being more rigid and fragile than the white
      matter. However, there are no reports regarding the association between aging an
      tensile and Finite Element Method (FEM). Therefore, FEM was used based on the
      data pertaining to the mechanical features of older bovine cervical spinal cord
      to explain the pathogenesis of CSM in elderly patients. Tensile tests were
      conducted for white and gray matter separately in young and old bovine cervical
      spinal cords, and compared with their respective mechanical features. Based on
      the data obtained, FEM analysis was further performed, which included static and
      dynamic factors to describe the internal stress distribution changes of the
      spinal cord. These results demonstrated that the mechanical strength of young
      bovine spinal cords is different from that of old bovine spinal cords. The gray
      matter of the older spinal cord was significantly softer and more resistant to
      rupture compared with that of younger spinal cords (P<0.05). Among the old,
      although the gray matter was more fragile than the white matter, it was similar
      to the white matter in terms of its rigidity (P<0.05). The in vitro data were
      subjected to three compression patterns. The FEM analysis demonstrated that the
      stress level rises higher in the old spinal cords in response to similar
      compression, when compared with young spinal cords. These results demonstrate
      that in analyzing the response of the spinal cord to compression, the age of
      patients is an important factor to be considered, in addition to the degree of
      compression, compression speed and parts of the spinal cord compression factor.

PMID- 29599830
TI  - beta-inducible gene-h3 promotes human breast carcinoma cell metastasis by
      activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.
AB  - Metastatic breast cancer is one of the most common metastatic tumors. Although
      studies have validated the role of beta-inducible gene-h3 (betaig-h3) in human
      biology and disease, the detailed mechanisms mediated by betaig-h3 in breast
      carcinoma metastasis remain unclear. Thus, the present study investigated the
      role and potential mechanism of betaig-h3 during breast carcinoma cell
      metastasis. The results indicated that the upregulation of betaig-h3
      significantly promotes the growth and inhibits the cisplatin-induced apoptosis of
      breast carcinoma cells. It was also demonstrated that betaig-h3 promoted the
      migration and invasion of human breast carcinoma cells in vitro and in vivo.
      Furthermore, the results demonstrated that betaig-h3 upregulated the overall
      expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and
      protein kinase B (Akt) in human breast carcinoma cells. By contrast, betaig-h3
      knockdown reversed the betaig-h3-mediated characteristics of breast carcinoma
      cells. Thus, the current study demonstrated that the PI3K/Akt signaling pathway
      serves a role in betaig-h3-induced human breast cancer cell metastasis and that
      betaig-h3 transfection enhances the metastatic potential of human breast
      carcinoma cells via the PI3K/Akt signaling pathway. These observations contribute
      to the understanding of the potential mechanism of human breast carcinoma cell
      growth and metastasis and suggest that betaig-h3 may be a promising therapeutic
      target for the treatment of human breast carcinoma.

PMID- 29599829
TI  - microRNA-10b expression and its correlation with molecular subtypes of early
      invasive ductal carcinoma.
AB  - The present study aimed to determine whether the expression of microRNA (miR)-10b
      was correlated with the molecular subtypes of early invasive ductal carcinoma of
      the breast. In situ hybridization was used to detect the expression of miR-10b in
      193 patients diagnosed with early invasive ductal carcinoma. Immunohistochemistry
      was performed to evaluate the expression of estrogen receptor (ER)-alpha,
      progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2).
      The positive expression rate of miR-10b in patients with early invasive ductal
      carcinoma with ER-alpha (+) or PR (+) was decreased compared with ER-alpha (-) or
      PR (-) patients (P<0.05). Furthermore, the positive expression rate of miR-10b in
      patients with Her-2 (-) was significantly increased compared with patients that
      were Her-2 (+) (P=0.031). The positive expression rate of miR-10b in the luminal
      B subtype was significantly decreased compared with that in the luminal A, Her-2
      and basal-like subtypes (P=0.037). In patients that were identified as miR-10b
      (+), the median disease-free survival time was significantly increased in
      patients that were ER-alpha (+)/PR (+)/Her-2 (-) compared with patients that were
      ER-alpha (-)/PR (-)/Her-2 (+) (P<0.05). In addition, the median disease-free
      survival time was significantly decreased in Her-2 overexpression and basal-like
      subtypes when compared with luminal A and B subtypes (P<0.05). The molecular
      subtype was an independent prognostic factor for early invasive ductal carcinoma
      (odds ratios for luminal B, Basal-like, and Her-2 overexpression were 2.900,
      5.232 and 4.214, respectively; all P<0.05). Positive expression of miR-10b may
      also be a prognostic risk factor (odds ratio >1), though this was not
      statistically significant (P>0.05). The present findings indicated that miR-10b
      positive expression was correlated with the expression of ER-alpha, Her-2 and the
      molecular subtypes of early invasive ductal carcinoma of the breast.

PMID- 29599831
TI  - Effect of curcumin on vascular endothelial growth factor in hypoxic HepG2 cells
      via the insulin-like growth factor 1 receptor signaling pathway.
AB  - To investigate the anti-angiogenic effect and underlying molecular mechanisms of
      curcumin on HepG2 cells under hypoxic conditions, insulin-like growth factor 1
      receptor (IGF-1R) knockout HepG2 cells were constructed using a clustered
      regularly interspaced short palindromic repeats/Cas9 genome-editing system.
      Hypoxic conditions were generated using cobalt chloride (CoCl2). An MTT assay was
      performed to measure the effects of curcumin on cell viability in hypoxia-induced
      IGF-1R knockout HepG2 cells, while western blot analysis was used to detect the
      expression of IGF-1R, phosphorylated (p)-protein kinase B (Akt), p-extracellular
      signal-regulated kinases (Erk)1/2, hypoxia-inducible factor-1alpha (HIF-1alpha)
      and vascular endothelial growth factor (VEGF). The results revealed that CoCl2 at
      low concentrations (50 and 100 uM) had no significant inhibitory effects on IGF
      1R knockout HepG2 cells. However, with increasing concentrations of CoCl2 and
      treatment time, cell viability decreased and was significantly reduced at 150,
      200 and 400 uM compared with the control group (P<0.05). The expression of HIF
      1alpha and VEGF were significantly increased when the cells were treated with 150
      or 200 uM CoCl2 compared with the control (P<0.05). With the increase of CoCl2
      concentration or the treatment time, the expression of HIF-1alpha and VEGF were
      upregulated gradually. Additionally, curcumin significantly inhibited the
      expression of p-Akt, p-Erk1/2, HIF-1alpha and VEGF in hypoxia-induced IGF-1R
      knockout HepG2 cells. In conclusion, the findings of the present study suggest
      that curcumin may serve a pivotal role in tumor suppression via the inhibition of
      IGF-1R-mediated angiogenesis under hypoxic conditions.

PMID- 29599832
TI  - Recombinant PEP-1-SOD1 improves functional recovery after neural stem cell
      transplantation in rats with traumatic brain injury.
AB  - The transplantation of neural stem cells (NSCs) has been demonstrated as a
      potential treatment strategy for traumatic brain injury (TBI). Cu, Zn-superoxide
      dismutase (SOD1) is an important antioxidant enzyme that detoxifies intracellular
      reactive oxygen species, thereby protecting cells from oxidative damage. PEP-1, a
      peptide carrier, is able to deliver full-length native peptides or proteins into
      cells. Therefore, the current study investigated the effect of the
      transplantation of NSCs in combination with PEP-1-SOD1 for the treatment of
      experimental TBI in rats. Initially, the effect of PEP-1-SOD1 on the
      proliferation of NSCs was evaluated by MTT assay. PEP-1-SOD1 (0.5, 2.5 and 4.5
      uM) significantly increased the proliferation rates of NSCs at 24, 48 and 72 h in
      a dose-dependent manner. PEP-1-SOD1 also promoted the differentiation of NSCs in
      vitro. The in vivo experiment showed that PEP-1-SOD1 in combination with NSC
      transplantation significantly improved the functional recovery of rats following
      TBI compared with NSC transplantation alone. A significant increase in brain
      aquaporin-4 (AQP4) mRNA and protein expression levels was observed 4 days post
      TBI in PEP-1-SOD1, NSCs and PEP-1-SOD1 + NSCs groups compared with the saline
      group. The PEP-1-SOD1 + NSCs group showed a further increase of AQP4 mRNA and
      protein expression levels compared with the NSCs and PEP-1-SOD1 groups. In
      conclusion, the current data suggests that PEP-1-SOD1 may promote the
      proliferation and differentiation of NSCs, and thereby improve the functional
      recovery of TBI model rats following NSCs transplantation through upregulating
      the expression of AQP4.

PMID- 29599833
TI  - Systemic tracking of diagnostic function modules for post-menopausal osteoporosis
      in a differential co-expression network view.
AB  - Post-menopausal osteoporosis is one of the most common bone diseases in women.
      The aim of the present study was to predict the diagnostic function modules from
      a differential co-expression gene network in order to enhance the current
      understanding of the biological processes and to promote the early prevention and
      intervention of post-menopausal osteoporosis. The diagnostic function modules
      were extracted from a differential co-expression network by the established
      protein-protein interaction (PPI) network analysis. First, significant genes were
      identified from the differential co-expression network, which were regarded as
      seed genes. Starting from the seed genes, the sub-networks in this disease,
      referred to as diagnostic function modules, were exhaustively searched and
      prioritized through a snowball sampling strategy to identify genes to accurately
      predict clinical outcomes. In addition, crucial function inference was performed
      for each diagnostic function module. Based on the microarray and PPI data, the
      differential co-expression network was constructed, which contained 1,607 genes
      and 4,197 interactions. A total of 110 seed genes were identified, and nine
      diagnostic modules that accurately distinguished post-menopausal osteoporosis
      from healthy controls were screened out from these seed genes. The diagnostic
      modules may be associated with five functional pathways with emphasis on
      metabolism. A total of nine diagnostic functional modules screened in the present
      study may be considered as potential targets for predicting the clinical outcomes
      of post-menopausal osteoporosis, and may contribute to the early diagnosis and
      therapy of osteoporosis.

PMID- 29599834
TI  - Improvement of postoperative cognitive dysfunction and attention network function
      of patients with ischemic cerebrovascular disease via dexmedetomidine.
AB  - The protective effect of dexmedetomidine on cognitive dysfunction and decreased
      attention network function of patients with ischemic cerebrovascular disease
      after stenting was investigated. Fifty-eight patients with ischemic
      cerebrovascular disease undergoing stenting in Guizhou Provincial People's
      Hospital were selected and randomly divided into control group (n=29) and
      dexmedetomidine group (n=29). The dexmedetomidine group was treated with
      dexmedetomidine before induced anesthesia, while the control group was given the
      same dose of normal saline; and the normal volunteers of the same age were
      selected as the normal group (n=29). At 3 days after operation, the levels of
      serum S100B and nerve growth factor (NGF) in each group were detected using the
      enzyme-linked immunosorbent assay, and the level of brain-derived neurotrophic
      factor (BDNF) was detected via western blotting. Montreal cognitive assessment
      (MoCA) and attention network test (ANT) were performed. Moreover, the cognitive
      function and attention network function, and the effects of dexmedetomidine on
      cognitive function and attention network function were evaluated. The
      concentrations of serum S100B and NGF in dexmedetomidine group was lower than
      those in control group (P<0.01). The results of western blotting showed that the
      levels of serum BDNF in control group and dexmedetomidine group were
      significantly lower than that in normal group (P<0.01), and it was higher in
      dexmedetomidine group than that in control group (P<0.01). Besides, both MoCA and
      ANT results revealed that the visual space and executive function scores,
      attention scores, delayed memory scores, targeted network efficiency and
      executive control network efficiency in dexmedetomidine group were obviously
      higher than those in control group (P<0.01). The cognitive function and attention
      network function of patients with ischemic cerebrovascular disease have a certain
      degree of damage, and the preoperative administration of dexmedetomidine can
      effectively improve the patient's cognitive dysfunction and attention network
      function after operation.

PMID- 29599835
TI  - Antibacterial effects of bacteriocins isolated from Lactobacillus rhamnosus (ATCC
      53103) in a rabbit model of knee implant infection.
AB  - Infection following orthopedic surgery is a major complication that can have
      serious implications on patient health. The present study aimed to investigate
      the antibacterial effects of bacteriocins obtained from Lactobacillus rhamnosus
      on a rabbit model of Staphylococcus aureus infection following knee replacement
      surgery. Blood samples were collected 1, 2, 3, 4 and 5 days after bacteriocin
      injection, and C-reactive protein (CRP) and interleukin (IL)-6 levels were
      measured using commercial ELISA kits. In addition, biofilm formation was
      evaluated by fluorescence microscopy. Bacteriocins were identified to exhibit
      significant inhibitory effects on Staphylococcus aureus biofilm formation, and on
      CRP and IL-6 levels in the serum, following surgery and infection (all P<0.05 vs.
      the control group). The results of the present study indicate that bacteriocins
      are a potential agent for the prevention of orthopedic postoperative infections.

PMID- 29599836
TI  - Acute kidney injury following the first stage of the ALPPS procedure: A case
      report.
AB  - Associating liver partition and portal vein ligation for staged hepatectomy
      (ALPPS) is a novel approach for performing liver resection, and the number of
      clinical applications of this technique has rapidly increased within recent
      years. ALPPS is important in patients who have insufficient residual liver volume
      and cannot undergo radical hepatic resection. The most common postoperative
      complications of ALPPS include biliary fistula and infection. To date,
      postoperative acute kidney injury following ALPPS has not been reported. The
      current study reports the case of a 63-year-old patient with hepatitis B-induced
      cirrhosis who underwent the first stage of ALPPS without completion of the second
      step. The patient developed postoperative acute kidney injury following ALPPS.
      The present case study suggests that the use of ALPPS in patients at risk of
      chronic renal damage should be approached with caution in order to avoid
      postoperative acute kidney injury. Furthermore, improvements in surgical
      techniques and skills of the surgeons performing the procedure are required to
      reduce the surgery duration and improve patient outcomes.

PMID- 29599837
TI  - Inhibition of prostate cancer DU145 cell growth with small interfering RNA
      targeting the SATB1 gene.
AB  - Prostate cancer is a common visceral cancer of men worldwide. It is important to
      develop a more effective treatment for prostate cancer to overcome the treatment
      resistance that occurs with recurrence. RNA interference has been demonstrated to
      be a powerful tool for gene knockdown and has potential as a cancer treatment. It
      has been previously demonstrated that staining of special AT-rich sequence
      binding protein 1 (SATB1) was stronger in prostatic carcinoma with metastasis
      compared with prostatic carcinoma without metastasis. In the present study, SATB1
      small interfering (si)RNA was transfected into prostate cancer DU145 cells and
      normal human lung fibroblast cells, and cell proliferation was investigated using
      a Cell Counting kit-8. Three siRNA were transfected into cells using siPORT Lipid
      Transfection agent, and blank control and negative control groups were
      established. The cells were harvested and SATB1 mRNA and protein expression was
      determined by reverse transcription-quantitative polymerase chain reaction and
      western blotting, respectively. DU145 cell adhesion, migration and invasion
      capabilities were determined using cell adhesion, Transwell and Transwell with
      Matrigel assays, respectively. Silencing SATB1 significantly inhibited DU145 cell
      growth, adhesion, migration and invasive capability in vitro, indicating that a
      SATB1-targeting siRNA was successfully engineered. The results of the present
      study suggest that SATB1 siRNA may be a potential agent for treating human
      prostate cancer.

PMID- 29599838
TI  - Assessment of recombinant plasmid expressing fusion antigen Ag85B-Rv3425 in
      management of acute tuberculosis infection in mice.
AB  - The emergence of drug-resistant tuberculosis (TB) and HIV-TB co-infection fuels
      an urgent need to develop novel therapeutic approaches, including therapeutic
      vaccines. Therapeutic vaccines have been proven to be a good strategy by inducing
      antigen specific immune responses against TB infection. In the present study, a
      recombinant plasmid based on lentiviral vector expressing fusion antigen Ag85B
      Rv3425 (A3), and was constructed the immunogenicity and treatment effects in TB
      mice were assessed. The results showed that A3 delivered by the plasmid could be
      expressed appropriately in vivo and induced higher production of tumor necrosis
      factor-alpha and interleukin-2 compared with A3 recombinant protein in mice.
      Moreover, the recombinant plasmid expressing A3 confered resistance to acute TB
      infection in mice, characterized by a reduction in the bacterial load in the
      lungs and spleen, as well as attenuated TB lesions in lung tissues. These results
      implicated that the recombinant plasmid based on lentiviral vector expressing A3
      is a potent and promising therapeutic agent to treat acute TB infection.

PMID- 29599839
TI  - Rapamycin protects against paraquat-induced pulmonary epithelial-mesenchymal
      transition via the Wnt/beta-catenin signaling pathway.
AB  - Paraquat (PQ) is a herbicide that is widely used in developing countries, and
      pulmonary fibrosisis one of the most typical features of PQ poisoning. The
      molecular mechanism underlying PQ toxicity is largely unknown, which makes it
      difficult to treat. In the present study, western blot analysis, reverse
      transcription-quantitative polymerase chain reaction and fluorescent
      immunostaining were used to analyze the effects of rapamycin on PQ-induced
      epithelial-mesenchymal transition (EMT) in A549 and MRC-5 cells. It was revealed
      that rapamycin significantly downregulated the mesenchymal cell marker, alpha
      smooth muscle actin, and significantly upregulated the epithelial cell marker, E
      cadherin, at mRNA and protein expression levels compared with the PQ group.
      Treatment with PQ significantly increased Wnt1, low-density lipoprotein receptor
      related protein (LRP)5, LRP6 and beta-catenin expression levels in A549 cells,
      while rapamycin significantly inhibited these effects of PQ. Activation of the
      Wnt signaling pathway using lithium chloride attenuated the inhibitory effects of
      rapamycin on PQ-induced EMT. In conclusion, rapamycin protects against PQ-induced
      pulmonary EMT via the Wnt/beta-catenin signaling pathway.

PMID- 29599840
TI  - Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc
      signaling in T-cell lymphoma cells.
AB  - The effectiveness of therapy combining dihydroartemisinin (DHA) and small
      interfering RNA targeting Notch1 (siNotch1) in T-cell lymphoma remains unknown.
      The present study explored the potential and possible mechanisms of combined
      dihydroarteminin, and siNotch1 therapy for T-cell lymphoma. It was demonstrated
      that the viability rates of siRNA-DHA-treated cells was significantly suppressed
      in comparison with those in control cells, control siRNA cells, siRNA-treated
      cells and DHA-treated cells (P<0.01). Additionally, there was a significant
      increase in cell apoptosis of siRNA-DHA-treated cells in comparison with those of
      control cells, control siRNA cells, siRNA-treated cells, DHA-treated cells
      (P<0.05). Furthermore, Notch1 and c-Myc mRNA and protein expression were
      decreased in siRNA-DHA-treated cells (P<0.05). The present study demonstrated
      that DHA combined with siNotch1 is able to suppress proliferation and promote
      apoptosis, and downregulate the expression of Notch1 and c-Myc mRNA and protein
      in T-cell lymphoma cells. Targeting Notch1/c-Myc signaling with siRNA and DHA may
      represent a novel strategy for treating human T-cell lymphoma.

PMID- 29599841
TI  - The anti-fatigue activities of Tuber melanosporum in a mouse model.
AB  - Tuber melanosporum (TM) is an edible fungus that exhibits antioxidant and anti
      tumor activity via its unique bioactive metabolites. The present study analyzed
      the anti-fatigue effects of TM using a BALB/c mouse model. The anti-fatigue
      properties of TM were evaluated by assessing the endurance of mice by performing
      forced swimming, rotary rod and running tests. Following 2 weeks TM treatment,
      hepatic and muscular ATP, and glycogen levels were increased in mice subjected to
      30 min swimming, compared with controls. Similarly, levels of serum lactic acid
      and lactic dehydrogenase were decreased in the same group, compared with the
      control. Additionally, TM treatment reduced reactive oxygen species and
      malondialdehyde levels, and increased superoxide dismutase and glutathione
      peroxidase levels in the muscle, liver and/or serum. The effect of TM on hormone
      levels was also investigated in the present study, as different efficacies of TM
      were observed in male and female mice. TM treatment increased serum levels of
      progesterone, estradiol and testosterone in female and male mice, whereas a
      decrease in serum luteinizing hormone levels was only observed in females. A
      decrease in serum follicle-stimulating hormone levels was identified in females,
      whereas an increase was observed in males. The current study demonstrated that
      the anti-fatigue effects of TM occur via the regulation of oxidative stress,
      energy metabolism and hormone levels.

PMID- 29599842
TI  - Therapeutic effects of simvastatin combined with kallistatin treatment for
      pediatric burn patients with sepsis.
AB  - The aim of the present study was to examine the combined efficacy of simvastatin
      and kallistatin treatment for pediatric burn sepsis. A total of 72 pediatric
      patients with burn sepsis were recruited and randomly divided into 3 groups,
      receiving simvastatin (40 mg/day), kallistatin (20 mg/day) or combined treatment.
      ELISA, reverse transcription-quantitative polymerase chain reaction, western
      blotting and flow cytometry were used to analyze the therapeutic effects of
      simvastatin and kallistatin. The results revealed that combined treatment in
      pediatric burn sepsis patients decreased the inflammatory cytokine tumor necrosis
      factor alpha and interleukin (IL)-1beta serum levels, whereas it increased IL-10
      and human leukocyte antigen-D related levels. In addition, administration of
      combined simvastatin and kallistatin decreased the blood urea nitrogen and serum
      creatinine levels in the patients. It was also demonstrated that Toll-like
      receptor 4 expression on the surface of monocytes was markedly decreased, while
      suppressor of cytokine signaling-3 expression was increased in the combined
      treatment group as compared with the kallistatin or simvastatin treatment alone.
      Combined treatment also promoted human endothelial cell (HEC) growth compared
      with the single treatment groups and inhibited the high mobility group box-1
      (HMGB1) levels, HMGB1-induced nuclear factor-kappaB activation and inflammatory
      gene expression levels in these cells. The study further demonstrated that
      combined treatment significantly decreased HEC apoptosis through the upregulation
      of B-cell lymphoma 2 (Bcl-2) and P53 expression levels, as well as downregulation
      of Bcl-2-associated X protein and caspase-3 levels. In conclusion, these
      observations indicated that combined treatment with simvastatin and kallistatin
      inhibited HEC apoptosis, which may be a potential therapeutic strategy for the
      treatment of pediatric burn sepsis patients.

PMID- 29599843
TI  - Platelet-rich plasma shows beneficial effects for patients with knee
      osteoarthritis by suppressing inflammatory factors.
AB  - Knee osteoarthritis is a degenerative disease that may develop due ageing,
      obesity, strain, congenital abnormal joints, joint deformity or trauma. It is
      caused by many factors, such as degradation of articular cartilage injury, joint
      edge and subchondral bone hyperplasia of reactivity. Platelet-rich plasma (PRP)
      is an autologous blood sample that contains highly concentrated platelets and
      multiple cell growth factors. PRP promotes synovial cell proliferation and
      differentiation and may recover cartilage morphology. In the present study, the
      clinical efficacy of PRP was investigated in patients with knee osteoarthritis
      aged between 18 and 30 years in a phase-III clinical study. Following an 8-week
      baseline, patients with knee osteoarthritis were randomized into once-weekly,
      double-blind treatment with PRP (2-14 ml) or placebo groups. The results
      indicated that patients with osteoarthritis treated with PRP had modulated plasma
      concentrations of inflammatory factors and pro-angiogenic factors compared with
      the placebo group. Treatment responses were assessed by median percent reduction
      in inflammatory and pro-angiogenic factors and these improved with PRP treatment
      compared with the placebo. Clinical data indicated that PRP alleviated knee
      osteoarthritis and reduced humoral and cellular immune responses that led to
      beneficial effects on histological parameters. Inflammation was significantly
      alleviated in patients receiving PRP compared with the placebo group. The most
      common treatment-emergent adverse events in the presence of PRP were hypertension
      and proteinuria. In conclusion, treatment with PRP for patients with knee
      osteoarthritis presented beneficial effects in alleviating joint inflammation,
      cartilage destruction and bone damage, and repairing joint tissue. These results
      suggested that PRP may be a potential therapeutic agent for knee osteoarthritis.

PMID- 29599844
TI  - Effect of the polyphenol composition BP-C3 on haematological and intestinal
      indicators of 5-fluorouracil toxicity in mice.
AB  - BP-C3 is a formulation, which comprises lignin-derived polyphenolic composition
      of benzenepolycarboxylic acids (BP-Cx-1) with iron complex, selenium, ascorbic
      acid and retinol, and possesses geroprotective activity. The present study
      examined the effect of BP-C3 (80 mg/kg, administered 18 times in total by gavage)
      on the development of haematological and intestinal manifestations of toxicity
      following 5-fluorouracil (5-FU; 150 mg/kg, administered once via intravenous
      injection) administration in outbred male Swiss-H Rappolovo (SHR) mice. The use
      of BP-C3 on therapeutic and preventative/therapeutic schedules demonstrated that
      it was protective against the toxic effect of 5-FU exerted on the lymphopoietic
      organs. Administering VR-S3 24 h after 5-FU (therapeutic schedule) had an effect
      on the recovery of leukopoiesis and prevented anaemia in the mice. In the mice
      that received 5-FU and 5-FU with BP-C3 prior to and following administration of
      the chemotherapeutic agent (preventative/therapeutic schedule), mild anaemia
      developed by day 7. Administration of BP-C3 without 5-FU did not affect blood
      cell differentiation in the mice. Thus, BP-C3, depending on the administration
      schedule, had different effects on the haematological parameters of
      haematopoietic organs and peripheral blood in mice exposed to 5-FU. BP-C3
      promoted intestinal crypt survival when administered on the
      preventative/therapeutic and therapeutic schedules, suggesting that the
      formulation protects the epithelium of the small intestine against damage by 5
      FU.

PMID- 29599845
TI  - Blood supply characteristics of pedunculated hepatocellular carcinoma prior to
      and following transcatheter arterial chemoembolization treatment: An angiographic
      demonstration.
AB  - Pedunculated hepatocellular carcinoma (P-HCC) is a rare type of HCC, defined as a
      carcinoma protruding from the liver with or without a pedicle with a low degree
      of liver invasion. The present study aimed to evaluate the characteristics of
      blood supply of P-HCC prior to and following transcatheter arterial
      chemoembolization (TACE) treatment. Angiographic findings prior to and following
      TACE treatment in 39 patients with P-HCC were analyzed retrospectively.
      Angiography performed at the first TACE session revealed 70 tumor-feeding
      arteries collectively in all patients, including 31/70 (44.0%) extrahepatic
      parasitic arteries in 23/39 patients (59.0%). The intrahepatic arteries served as
      the main blood supply to P-HCC in all patients. Extrahepatic collateral blood
      supplies to P-HCCs were significantly associated with larger tumor diameter
      (chi2=164.000, P<0.001), but not tumor location (chi2=7.358, P=0.061). Following
      repeated TACE treatment, all angiographies revealed a total of 131 tumor feeding
      arteries collectively in all patients, including intrahepatic arteries (54/131)
      and extrahepatic collateral arteries (78/131) in 31 patients (79.5%). Compared
      with angiographies performed at the initial TACE treatment, these results also
      demonstrated an increase in the number of extrahepatic collateral arteries, which
      produced 47 new blood vessels (chi2=4.278, P=0.039). P-HCC tumor lesions readily
      acquired a parasitic blood supply from adjacent vessels following repeated TACE.
      Intrahepatic arteries functioned as the main blood supply for P-HCC, whereas
      extrahepatic collateral arteries were complementary to P-HCC, regardless of
      whether the patient was pre- or post-TACE. Extrahepatic collateral supplies to P
      HCCs that originated from adjacent vessels were rich, were closely associated
      with tumor size, and were prone to be newly established following repeated TACE.

PMID- 29599846
TI  - Reference values for fatigued versus non-fatigued limb symmetry index measured by
      a newly designed single-leg hop test battery in healthy subjects: a pilot study.
AB  - Purpose: There is sparse evidence for return to sport criteria after knee injury.
      Functional performance deficits, particularly in fatigued muscular condition,
      should be verified prior to the attempt to return to high-risk pivoting sports.
      The purpose of this study was to generate reference values for the limb symmetry
      index (LSI) of healthy subjects in fatigued and non-fatigued muscular condition
      in a newly designed test battery. Methods: Forty-two healthy subjects [22
      females, 20 males; mean (SD) age 30.4 (6.6) years] were evaluated using a test
      battery consisting of an isometric strength test, a series of five single-leg hop
      tests and an integrated fatigue protocol. Subjective physical activity was
      assessed with the Tegner Activity Scale (TAS). The cut-off values for healthy
      subjects were calculated considering the fifth percentile as the minimum
      reference value for the LSI and single-leg hop distance. Results: The mean (SD)
      overall LSI was 98.8% (4.6). No significant gender or age specific differences in
      limb symmetry were observed. The comparison of the non-fatigued LSI with the
      overall LSI revealed no clinically relevant change due to muscular fatigue.
      Repeated measures ANOVA revealed a significant within effect on fatigue/non
      fatigue condition (F(1,38) = 18.000; p < 0.001, eta2 = 0.321) on absolute single
      leg hop distance. Moreover, a significant between effect on the TAS-parameter
      (F(1,38) = 5.928; p = 0.020, eta2 = 0.135 between: TAS <= 5/TAS > 5) and on
      gender (F(1,38) = 23.956; p < 0.001, eta2 = 0.387) could be detected.
      Conclusions: The absolute jumping distance in the single-leg hop for distance was
      significantly reduced due to fatigue. No clinically relevant effect of muscular
      fatigue was observed on limb symmetry in our study sample. Gender and physical
      activity are important factors to be considered when interpreting reference
      values.

PMID- 29599848
TI  - The Co-creation and Feasibility of a Compassion Training as a Follow-up to
      Mindfulness-Based Cognitive Therapy in Patients with Recurrent Depression.
AB  - The aim of this study was to assess the feasibility, acceptability and
      preliminary effectiveness of Mindfulness - Based Compassionate Living (MBCL) as a
      follow-up intervention to Mindfulness Based Cognitive Therapy in adults with
      recurrent depression. We conducted an uncontrolled study in 17 patients with
      recurrent depression, in two successive groups. The first group contained novices
      to compassion training (N = 14); in the second group, ten of these participated
      again, in addition to three new participants (N = 13). The overall group
      contained 15 females and 2 males, aged between 37 and 71. The MBCL program was
      qualitatively evaluated using post-intervention focus group interviews in both
      groups. In addition, self-report questionnaires assessing depressive symptoms,
      worry and both self-compassion and mindfulness skills were administered before
      and after MBCL. No patients dropped out of the intervention. Average attendance
      was 7.52 (SD 0.73) out of eight sessions. Helpful elements were theory on the
      emotion regulation systems, practicing self-compassion explicitly and embodiment
      of a compassionate attitude by the teachers. Unhelpful elements were the lack of
      a clear structure, lack of time to practice compassion for self and the
      occurrence of the so-called back draft effect. We adapted the program in
      accordance with the feedback of the participants. Preliminary results showed a
      reduction in depressive symptoms in the second group, but not in the first group,
      and an increase in self-compassion in both groups. Worry and overall mindfulness
      did not change. MBCL appears to be feasible and acceptable for patients suffering
      from recurrent depressive symptoms who previously participated in MBCT. Selection
      bias may have been a factor as only experienced and motivated participants were
      used; this, however, suited our intention to co-create MBCL in close
      collaboration with knowledgeable users. Examination of the effectiveness of MBCL
      in a sufficiently powered randomised controlled trial is needed.

PMID- 29599847
TI  - A multiplatform approach identifies miR-152-3p as a common epigenetically
      regulated onco-suppressor in prostate cancer targeting TMEM97.
AB  - Background: Prostate cancer (PCa) is a major cause of morbidity and mortality in
      men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly
      differentiated tumors. Nonetheless, the underlying mechanisms are still elusive.
      Herein, using combined analysis of microRNAs expression and genomewide DNA
      methylation, we aimed to identify epigenetically downregulated microRNAs in PCa.
      Results: We found that miR-152-3p was underexpressed in PCa and that lower
      expression levels were associated with promoter hypermethylation in accordance
      with TCGA dataset analysis. Functional in vitro assays suggest that miR-152-3p
      suppresses cell viability and invasion potential, whereas it promotes cell cycle
      arrest at S and G2/M phases. Additionally, miR-152-3p expression was associated
      with longer disease-free survival in PCa patients from TCGA. Finally, TMEM97,
      which is overexpressed in PCa, was identified as a novel miR-152-3p target gene.
      Conclusions: Our findings demonstrate the advantages of using a combinatory
      approach to identify microRNAs downregulated due to aberrant promoter
      methylation. MiR-152-3p downregulation and promoter methylation was found to be
      prevalent in primary PCa, which impairs its role in control of cell viability,
      cell cycle regulation and invasion.

PMID- 29599849
TI  - The Integration of the Workable Range Model into a Mindfulness-Based Stress
      Reduction Course: a Practice-Based Case Study.
AB  - Didactic teaching about stress is part of the Mindfulness-Based Stress Reduction
      (MBSR) curriculum. The content and methods of integrating conceptual teaching
      within the experiential pedagogy are rarely explored. Workable range is a model
      of stress and emotion regulation that illustrates patterns of physical, emotional
      and cognitive reactivity in relation to mindful presence. This is a qualitative
      case study of the inclusion of the workable range model into an MBSR course as a
      refinement of the didactic teaching about stress. The focus is to illuminate how
      the inclusion worked in practice. Ten staff, on a MBSR course in a higher
      educational setting, were recruited as participant researchers with an overlap
      between their own first-person investigation during the course and the research
      data. Adapted diagrams and written answers to two question schedules, completed
      as reflective exercises within the course, were analysed thematically using
      template analysis. This revealed how participant researchers engaged with and
      intuitively used the model to notice and describe their own patterns of feeling
      balanced or stressed and explore how they related to those experiences. How
      learning the model integrated with MBSR and the applicability of workable ranges
      as a teaching resource in MBSR is discussed. The study highlights questions about
      how conceptual and experiential teaching and learning interrelate in mindfulness
      based interventions. There is scope for further research using mindfulness
      practice as a first-person methodology to investigate the processes within
      mindfulness-based programs.

PMID- 29599850
TI  - How Is Stress Reduced by a Workplace Mindfulness Intervention? A Qualitative
      Study Conceptualising Experiences of Change.
AB  - Mindfulness-based interventions are effective as curative and preventative
      approaches to psychological health. However, the mechanisms by which outcomes are
      secured from such interventions when delivered in the workplace, and to a
      stressed workforce, are not well understood. The aim of the present study was to
      elicit and analyse accounts from past participants of a workplace mindfulness
      intervention in order to generate a preliminary model of how positive benefits
      appear to be secured. In-depth, semi-structured interviews were completed with 21
      employees of a higher education institution who had completed an eight-week
      intervention based on Mindfulness-Based Stress Reduction, adapted for the
      workplace. Interviews invited participants to recount their experiences of the
      intervention and its impact, if any, on their work life. Aspects of the interview
      data that pertained to intervention experience and positive benefits were
      analysed using a version of grounded theory, leading to the generation of a
      provisional model of how positive change occurred. The model suggests that
      discrete, temporal experiences build on each other to generate multiple, positive
      benefits. As anticipated in mindfulness-based interventions, enhanced attentional
      capacity was important, but our provisional model also suggests that resonance,
      self-care, detection of stress markers, perceiving choice, recovering self-agency
      and upward spiralling may be central mechanisms that lead to positive outcomes.
      Understanding mechanisms of change may help support participant engagement and
      trust in work-based mindfulness programmes, and enhance participants' ability to
      apply mindfulness in their work life.

PMID- 29599851
TI  - Potential Mechanisms of Mindfulness in Improving Sleep and Distress.
AB  - The mechanisms of mindfulness-improved sleep quality are not extensively studied.
      Recently, attention monitoring/awareness and acceptance in mindfulness have been
      proposed to be the underlying mechanisms that tackle distress and related
      disorders. The current study tested if acceptance moderated the relationship of
      awareness with psychological distress and sleep quality, and verified that
      psychological distress mediated the relationship between mindfulness and sleep
      quality in a group of community-dwelling healthy adults. Three hundred and sixty
      four healthy Chinese non-meditators (age 18-65, 59% female) completed a set of
      online self-reported questionnaires in Chinese via SurveyMonkey. Awareness and
      acceptance were measured by Observe and Nonreact facets in the Five Facet
      Mindfulness Questionnaire (FFMQ), respectively. General psychological distress
      levels and sleep quality were reflected in the global score of the Depression
      Anxiety and Stress Scales (DASS) and the Pittsburgh Sleep Quality Index (PSQI),
      respectively. Model 1 and model 8 in the PROCESS macro for SPSS were used to
      assess the moderation and moderated mediation effects. Increased level of
      acceptance (Nonreact) weakened the positive relationship between awareness
      (Observe) and poor sleep quality (beta = -0.0154, p = 0.0123), which was
      partially mediated through perceived psychological distress (beta = -0.0065, 95%
      bias-corrected bootstrap CI = -0.0128, -0.0004) in a group of community-dwelling
      healthy adults. Our findings suggested that awareness and acceptance could be the
      mechanisms of mindfulness interventions in improving sleep quality, partly via
      reducing psychological stress.

PMID- 29599852
TI  - Mindfulness Dampens Cardiac Responses to Motion Scenes of Violence.
AB  - Mindfulness is linked with improved regulatory processes of attention and
      emotion. The potential benefits of mindfulness are vast, including more positive
      emotional states and diminished arousal in response to emotional stimuli. This
      study aims to expand of the current knowledge of the mechanisms of mindfulness by
      relating the latter to cardiovascular processes. The paper describes two studies
      which investigated the relationship of trait mindfulness to self-report measures
      of emotions elicited during a violent video clip and cardiovascular responses to
      the clip. Both studies recruited male and female participants, mainly university
      undergraduate students. The clip was 5-min-long and evoked mainly feelings of
      tension and disgust. In study 1, we found that higher scores for trait
      mindfulness were associated with increased scores for valence (r = .370, p =
      .009), indicating a more positive interpretation of the clip. In study 2, the
      average heart rate during the clip was lower than during the preceding (p < .05)
      and following (p < .01) non-exposure conditions. Higher trait mindfulness was
      related to diminished heart rate reactivity (r = -.364, p = .044) and recovery (r
      = -.415, p = .020). This latter effect was obtained only when trait anxiety was
      used as a statistical covariate. Additionally, increased trait mindfulness was
      accompanied by higher resting heart rate (r = .390, p = .027). These outcomes
      suggest that mindfulness is linked with reductions in negative feelings evoked by
      violent motion stimuli.

PMID- 29599853
TI  - An Investigation of the Factor Structure of the Self-Compassion Scale.
AB  - The Self-Compassion Scale (SCS) is the most widely used measure of self
      compassion. The scale is constructed of six factors measuring positive and
      negative components of compassion. Support for this factor structure has been
      subject to debate and alternative factor structures have been proposed. We tested
      the proposed factor structures against existing models of the SCS including one
      derived from an exploratory factor analysis of our data. Respondents (n = 526)
      completed the original version of the SCS online at two time points, at baseline
      (time 1) and 2.5 months later (n = 332, time 2). Exploratory factor analysis
      (EFA) was carried out on time 1 data and confirmatory factor analyses (CFA) were
      conducted on time 2 data and retested using time 1 data. The EFA yielded a five
      factor model. CFA was used to compare the following models: Neff's original six
      factor correlated and higher-order models; a single-factor, two-factor, five
      factor model (as suggested by the EFA) and a bi-factorial model. The bi-factorial
      model was the best fit to the data followed by the six-factor correlated model.
      Omega indices were calculated and yielded support for the bi-factorial model of
      SCS. In conclusion, this study supports the use of the six-factor scoring method
      of the SCS and the use of an overarching self-compassion score.

PMID- 29599855
TI  - Muscle Activity in Upper-Body Single-Joint Resistance Exercises with Elastic
      Resistance Bands vs. Free Weights.
AB  - Elastic resistance bands require little space, are light and portable, but their
      efficacy has not yet been established for several resistance exercises. The main
      objective of this study was to compare the muscle activation levels induced by
      elastic resistance bands versus conventional resistance training equipment
      (dumbbells) in the upper-body resistance exercises flyes and reverse flyes. The
      level of muscle activation was measured with surface electromyography in 29 men
      and women in a cross-over design where resistance loadings with elastic
      resistance bands and dumbbells were matched using 10-repetition maximum loadings.
      Elastic resistance bands induced slightly lower muscle activity in the muscles
      most people aim to activate during flyes and reverse flies, namely pectoralis
      major and deltoideus posterior, respectively. However, elastic resistance bands
      increased the muscle activation level substantially in perceived ancillary
      muscles, that is deltoideus anterior in flyes, and deltoideus medius and
      trapezius descendens in reverse flyes, possibly due to elastic bands being a more
      unstable resistance modality. Overall, the results show that elastic resistance
      bands can be considered a feasible alternative to dumbbells in flyes and reverse
      flyes.

PMID- 29599854
TI  - The Role of Parathyroid Hormone and Vitamin D Serum Concentrations in Patients
      with Cardiovascular Diseases.
AB  - 25-hydroxyvitamin D (25(OH)D) plays a crucial role in human homeostasis. Its
      deficiency (vitamin D deficiency-VDD), being common in European population,
      combined with elevated concentration of parathyroid hormone (PTH), represents a
      vicious cycle of mechanisms leading to heart failure (HF). Despite several papers
      published in that field, the effect of VDD and PTH concentration on
      cardiovascular system remains unequivocal; thus, the aim of the study was to
      compare these data among HF and non-HF patients being prospectively enrolled into
      the study during hospital stay in the cardiology ward. Patients with HF had
      higher PTH concentration (85.0 +/- 52.6 versus 64.5 +/- 31.7, p <= 0.02) compared
      to non-HF patients. Mean PTH values were associated with the clinical status
      expressed by the New York Heart Association class (NYHA class) ("0"-66.04, "I"
      56.57, "II"-72.30, "III"-85.59, and "IV"-144.37 pg/ml, p <= 0.00004).
      Interestingly, neither 25(OH)D (31.5 versus 29.7 ng/ml, p <= ns) nor phosphorus
      (P) (1.23 versus 1.18 mmol/l, p <= ns) nor total calcium (Ca2+) concentration
      (2.33 versus 2.37 mmol/l, p <= ns) differed among the groups. Reassuming PTH
      serum concentration in contrary to 25(OH)D, P and Ca2+ are significantly raised
      among the patients with HF and shows significant relationship with the clinical
      status expressed by the NYHA class.

PMID- 29599856
TI  - Influence of Dynamic Neuromuscular Stabilization Approach on Maximum Kayak
      Paddling Force.
AB  - The purpose of this study was to examine the effect of Dynamic Neuromuscular
      Stabilization (DNS) exercise on maximum paddling force (PF) and self-reported
      pain perception in the shoulder girdle area in flatwater kayakers. Twenty male
      flatwater kayakers from a local club (age = 21.9 +/- 2.4 years, body height =
      185.1 +/- 7.9 cm, body mass = 83.9 +/- 9.1 kg) were randomly assigned to the
      intervention or control groups. During the 6-week study, subjects from both
      groups performed standard off-season training. Additionally, the intervention
      group engaged in a DNS-based core stabilization exercise program (quadruped
      exercise, side sitting exercise, sitting exercise and squat exercise) after each
      standard training session. Using a kayak ergometer, the maximum PF stroke was
      measured four times during the six weeks. All subjects completed the Disabilities
      of the Arm, Shoulder and Hand (DASH) questionnaire before and after the 6-week
      interval to evaluate subjective pain perception in the shoulder girdle area.
      Initially, no significant differences in maximum PF and the DASH questionnaire
      were identified between the two groups. Repeated measures analysis of variance
      indicated that the experimental group improved significantly compared to the
      control group on maximum PF (p = .004; Cohen's d = .85), but not on the DASH
      questionnaire score (p = .731) during the study. Integration of DNS with
      traditional flatwater kayak training may significantly increase maximum PF, but
      may not affect pain perception to the same extent.

PMID- 29599857
TI  - Modelling and Predicting Backstroke Start Performance Using Non-Linear and Linear
      Models.
AB  - Our aim was to compare non-linear and linear mathematical model responses for
      backstroke start performance prediction. Ten swimmers randomly completed eight 15
      m backstroke starts with feet over the wedge, four with hands on the highest
      horizontal and four on the vertical handgrip. Swimmers were videotaped using a
      dual media camera set-up, with the starts being performed over an instrumented
      block with four force plates. Artificial neural networks were applied to predict
      5 m start time using kinematic and kinetic variables and to determine the
      accuracy of the mean absolute percentage error. Artificial neural networks
      predicted start time more robustly than the linear model with respect to changing
      training to the validation dataset for the vertical handgrip (3.95 +/- 1.67 vs.
      5.92 +/- 3.27%). Artificial neural networks obtained a smaller mean absolute
      percentage error than the linear model in the horizontal (0.43 +/- 0.19 vs. 0.98
      +/- 0.19%) and vertical handgrip (0.45 +/- 0.19 vs. 1.38 +/- 0.30%) using all
      input data. The best artificial neural network validation revealed a smaller mean
      absolute error than the linear model for the horizontal (0.007 vs. 0.04 s) and
      vertical handgrip (0.01 vs. 0.03 s). Artificial neural networks should be used
      for backstroke 5 m start time prediction due to the quite small differences among
      the elite level performances.

PMID- 29599858
TI  - The Effects of Cryotherapy on Knee Joint Position Sense and Force Production
      Sense in Healthy Individuals.
AB  - The proprioceptive information received from mechanoreceptors is potentially
      responsible for controlling the joint position and force differentiation.
      However, it is unknown whether cryotherapy influences this complex mechanism.
      Previously reported results are not universally conclusive and sometimes even
      contradictory. The main objective of this study was to investigate the impact of
      local cryotherapy on knee joint position sense (JPS) and force production sense
      (FPS). The study group consisted of 55 healthy participants (age: 21 +/- 2 years,
      body height: 171.2 +/- 9 cm, body mass: 63.3 +/- 12 kg, BMI: 21.5 +/- 2.6). Local
      cooling was achieved with the use of gel-packs cooled to -2 +/- 2.5 degrees C and
      applied simultaneously over the knee joint and the quadriceps femoris muscle for
      20 minutes. JPS and FPS were evaluated using the Biodex System 4 Pro apparatus.
      Repeated measures analysis of variance (ANOVA) did not show any statistically
      significant changes of the JPS and FPS under application of cryotherapy for all
      analyzed variables: the JPS's absolute error (p = 0.976), its relative error (p =
      0.295), and its variable error (p = 0.489); the FPS's absolute error (p = 0.688),
      its relative error (p = 0.193), and its variable error (p = 0.123). The results
      indicate that local cooling does not affect proprioceptive acuity of the healthy
      knee joint. They also suggest that local limited cooling before physical activity
      at low velocity did not present health or injury risk in this particular study
      group.

PMID- 29599859
TI  - Functional Movements in Japanese Mini-Basketball Players.
AB  - Functional movement screen (FMS) has been used to establish normative data and
      determine potential injury risk for young adults and athletes, but there are few
      data in elementary school-age children. The purpose of this study was to
      establish fundamental values for the FMS in elementary school-age mini-basketball
      players. Secondary purposes were to examine relationships between functional
      movement patterns and age, peak height velocity (PHV), and body mass index (BMI),
      and to compare functional movement patterns between boys and girls and between
      individuals with and without a history of injury. The mean composite FMS score
      was 16.5 +/- 2.2 (16.5 +/- 2.4 for boys, 16.5 +/- 1.7 for girls). The composite
      FMS score was positively correlated with age (r = .312) and negatively correlated
      with the BMI (r = - .371). However, the FMS score was not correlated with PHV or
      with PHV age. The FMS score was not different between boys and girls or between
      individuals who reported a previous injury and those who did not. However, boys
      in the mini-basketball teams performed better than girls on the trunk stability
      push-up and rotary stability tests. Age and the body mass index were
      significantly associated with better and poorer functional movement,
      respectively.

PMID- 29599860
TI  - Can Supplementation of Vitamin D Improve Aerobic Capacity in Well Trained Youth
      Soccer Players?
AB  - There is no clear evidence that vitamin D effectively improves physical capacity
      in high-level athletes. The aim of this study was to confirm that vitamin D
      supplementation of soccer players during eight-week high-intensity training would
      have a significant effect on their aerobic capacity. The subjects were divided
      into two groups: the experimental one that was supplemented with vitamin D (SG, n
      = 20), and the placebo group (PG, n = 16), not supplemented with vitamin D. All
      the players were subjected to the same soccer training described as High
      Intensity Interval Training (HIIT). The data of the vitamin D level, PWC170,
      lactate threshold (LT) were collected just before and after the intervention. A
      significant increase in vitamin D concentration (119%) was observed in the
      supplemented group, while the non-supplemented group showed a decrease of 8.4%.
      The studied subjects improved VO2max results by 20% in the SG, and by 13% in the
      PG. The improvement in velocity at the LT was similar in both groups. Results of
      this study show that vitamin D can have a positive, though moderate, effect on
      aerobic performance in players subjected to high-intensity training in the form
      of small-sided games for 8 weeks.

PMID- 29599861
TI  - The Effects of Aerobic Exercise and Gaming on Cognitive Performance.
AB  - The purpose of our study was to investigate the effects of video gaming, aerobic
      exercise (biking), and the combination of these two activities on the domains of
      cognitive performance: selective attention, processing speed, and executive
      functioning. The study was a randomized clinical trial with 40 subjects (mean age
      23.7 +/- 1.8 years) randomized to one of four thirty-minute conditions: video
      gaming, biking, simultaneous gaming and biking, and a control condition.
      Cognitive performance was measured pre and post condition using the Stroop test
      and Trails B test. A mixed design was utilized. While video gaming, biking,
      simultaneous gaming and biking conditions improved selective attention and
      processing speed (p < 0.05), only the bike condition improved the highest order
      of cognitive performance, executive function (p < 0.01). There were no changes in
      cognitive performance for the control condition. Previous studies have shown that
      if tasks approach the limits of attentional capacity there is an increase in the
      overall chance for errors, known as the dual-task deficit. Simultaneous biking
      and gaming may have surpassed attentional capacity limits, ultimately increasing
      errors during the executive function tests of our cognitive performance battery.
      The results suggest that the fatiguing effects of a combined physically and
      mentally challenging task that extends after the exercise cessation may overcome
      the eventual beneficial cognitive effects derived from the physical exercise.

PMID- 29599862
TI  - Fatigue Responses in Various Muscle Groups in Well-Trained Competitive Male
      Players after a Simulated Soccer Game.
AB  - We examined the degree of post-game fatigue and the recovery pattern in various
      leg and upper-body muscle groups after a simulated soccer game. Well-trained
      competitive male soccer players (n = 12) participated in the study. The players
      completed the Copenhagen Soccer Test, a 2 x 45 min simulated soccer protocol,
      following baseline measures of maximal voluntary contractions of multiple muscle
      groups and systemic markers of muscle damage and inflammation at 0, 24 and 48 h
      into recovery. All muscle groups had a strength decrement (p <= 0.05) at 0 h post
      match with knee flexors (14 +/- 3%) and hip abductors (6 +/- 1%) demonstrating
      the largest and smallest impairment. However, 24 h into recovery all individual
      muscles had recovered. When pooled in specific muscle groups, the trunk muscles
      and knee joint muscles presented the largest decline 0 h post-match, 11 +/- 2%
      for both, with the performance decrement still persistent (4 +/- 1%, p <= 0.05)
      for trunk muscles 24 h into recovery. Large inter-player variations were observed
      in game-induced fatigue and recovery patterns in the various muscle groups.
      Markers of muscle damage and inflammation peaked 0 h post-match (myoglobin) and
      24 h into recovery (creatine kinase), respectively, but thereafter returned to
      baseline. Intermittent test performance correlated with creatine kinase activity
      24 h after the Copenhagen Soccer Test (r = -0.70; p = 0.02). In conclusion, post
      game fatigue is evident in multiple muscle groups with knee flexors showing the
      greatest performance decrement. Fatigue and recovery patterns vary markedly
      between muscle groups and players, yet trunk muscles display the slowest
      recovery.

PMID- 29599863
TI  - Aerobic Fitness of Starter and Non-Starter Soccer Players in the Champion's
      League.
AB  - To identify individual response patterns in selected aerobic fitness variables of
      regular starters (ST; N = 7) and non-starters (Non-ST; N = 10), top level
      professional soccer players were tested for maximal oxygen uptake (VO2max),
      velocity at 4 mM of lactate (V4), velocity at maximal oxygen uptake (nuVO2max)
      and oxygen pulse (O2-pulse) in July and December following consecutive periods of
      fixture congestion. V4 was the only variable that increased significantly in
      December compared to July (15.1 +/- 0.5 vs. 14.6 +/- 0.5, p = 0.001). There was
      an almost certain beneficial large mean team change for V4 (ES = 1.2 (0.67;
      1.57), 100/0/0), while beneficial mean team changes were less likely for nuVO2max
      and O2-pulse [ES = 0.31 (-0.08; 0.70), 68/30/2 and ES = 0.24 (0.01; 0.49),
      64/36/0, respectively] and unclear for VO2max (ES = 0.02 (-0.31; 0.70),
      18/69/13). With the exception of V4 where 10 out of 17 players (7 ST and 3 Non
      ST) showed positive changes higher than the biological variability, all other
      variables were characterized by a substantial proportion of changes lower than
      the biological variability. The present study demonstrated that aerobic fitness
      variables that require maximal effort may be characterized by greater variability
      of the individual response pattern compared to that of submaximal aerobic fitness
      variables irrespective of the accumulated game time. Submaximal aerobic fitness
      variables appear to be more informative in the physiological evaluation of top
      level soccer players and this may be an advantage during exposure to periods of
      consecutive games.

PMID- 29599864
TI  - Urinary Steroid Profile in Ironman Triathletes.
AB  - The aim of this study was to determine variations in the urinary steroid profile
      of triathletes following an Ironman event. A total of 10 male participants (age =
      36.0 +/- 1.27 years; body height = 179.29 +/- 10.77 cm; body mass = 74.50 +/-
      1.04 kg) completed an Ironman Championship. Urine samples were collected before,
      immediately after, and 24 hours following the race. Gas chromatography-mass
      spectrometry (GC/MS) was used to detect and quantify catabolic and anabolic
      hormones: Androsterone, Dehydroepiandrosteone (DHEA), Androstenedione and
      Testosterone (T), Betaestradiol, Estrone, Progesterone, Cortisol (C), Cortisone,
      Tetrahydrocortisol (THE) and Tetrahydrocortisone (THF). These were measured in
      their glucuroconjugated and free forms. Androsterone (3297.80 +/- 756.83 vs.
      2154.26 +/- 1375.38), DHEA (47.80 +/- 19.21 vs. 32.62 +/- 15.96) and Beta
      estradiol (59.36 +/- 11.7 vs. 41.67 +/- 10.59) levels decreased after the event.
      The significant decrease of DHEA (47.80 +/- 19.21 vs. 32.11 +/- 14.03) remained
      at 24 hours. Cortisol (200.38 +/- 56.60 vs. 257.10 +/- 74.00) and THE (238.65 +/-
      81.55 vs. 289.62 +/- 77.13) increased after exercise and remained elevated 24
      hours later (200.38 +/- 56.60 vs. 252.48 +/- 62.09; 238.65 +/- 81.55 vs. 284.20
      +/- 66.66). The following anabolic/catabolic ratios fell after exercise: T/C
      (0.85 +/- 0.54 vs. 0.54 +/- 0.29), T/THE (0.66 +/- 0.29 vs. 0.40 +/- 0.08),
      T/THE+THF (0.38 +/- 0.17 vs. 0.24 +/- 0.06), DHEA/THE (0.22 +/- 0.05 vs. 0.12 +/-
      0.05), DHEA/THF (0.34 +/- 0.02 vs. 0.21 +/- 0.01) and DHEA/THE+THF (0.12 +/- 0.02
      vs. 0.08 +/- 0.03). The steroid profile showed that athletes were fatigued after
      finishing the competition and a catabolic state remained 24 hours later.

PMID- 29599865
TI  - Effect of Compression Garments on Physiological Responses After Uphill Running.
AB  - Limited practical recommendations related to wearing compression garments for
      athletes can be drawn from the literature at the present time. We aimed to
      identify the effects of compression garments on physiological and perceptual
      measures of performance and recovery after uphill running with different pressure
      and distributions of applied compression. In a random, double blinded study, 10
      trained male runners undertook three 8 km treadmill runs at a 6% elevation rate,
      with the intensity of 75% VO2max while wearing low, medium grade compression
      garments and high reverse grade compression. In all the trials, compression
      garments were worn during 4 hours post run. Creatine kinase, measurements of
      muscle soreness, ankle strength of plantar/dorsal flexors and mean performance
      time were then measured. The best mean performance time was observed in the
      medium grade compression garments with the time difference being: medium grade
      compression garments vs. high reverse grade compression garments. A positive
      trend in increasing peak torque of plantar flexion (60o.s-1, 120o.s-1) was found
      in the medium grade compression garments: a difference between 24 and 48 hours
      post run. The highest pain tolerance shift in the gastrocnemius muscle was the
      medium grade compression garments, 24 hour post run, with the shift being +11.37%
      for the lateral head and 6.63% for the medial head. In conclusion, a beneficial
      trend in the promotion of running performance and decreasing muscle soreness
      within 24 hour post exercise was apparent in medium grade compression garments.

PMID- 29599866
TI  - Impact of Official Matches on Soccer Referees' Power Performance.
AB  - The evaluation of match officials' neuromuscular performance is now an important
      consideration and the vertical jump test is considered suitable for assessing
      lower limb power, partly because it is directly related to refereeing. The aim of
      this study, therefore, was to determine the effect of soccer matches on match
      officials' vertical jump performance by assessing various biomechanical
      variables. Eighteen field referees (FRs) and 36 assistant referees (ARs) who
      officiated in 18 official matches participated in this study. Before the match,
      at half time and immediately after the match, officials performed two
      countermovement jumps. Flight phase time (FT), maximum force production
      (MFpropulsion), time to production of maximum force (TMFpropulsion), production
      of maximum power (MP), maximum landing force (MFlanding) and time to
      stabilization (TTS) were calculated for all jumps. There was a tendency for match
      officials' jumping performance to improve after matches than beforehand (FR:
      effect size (ES) = 0.19 +/- 0.36, possibly trivial; AR: ES = 0.07 +/- 0.17,
      likely trivial). There were also likely small and very likely moderate
      differences between FRs' MP in pre-match and half-time jumps (ES = 0.46 +/- 0.47)
      and in their pre- and post-match jumps (ES = 0.71 +/- 0.48). These results
      indicate that refereeing soccer matches does not reduce vertical jump
      performance; the subsequent neuromuscular fatigue is not sufficient to affect
      landing technique.

PMID- 29599867
TI  - Variance in Prominence Levels and in Patterns of Passing Sequences in Elite and
      Youth Soccer Players: A Network Approach.
AB  - The aim of this study was to quantify the prominence levels of elite and highly
      competitive young soccer players. This study also analyzed the variation in
      general network properties at different competitive levels and periods of the
      season. A total of 132 matches, played by 28 teams during the 2015/2016 season,
      were analyzed. The results revealed significant differences in the composition of
      general network measures considering the competitive level (p = 0.002; ES =
      0.077) and according to the location of the match (p = 0.001; ES = 0.147). There
      were positive correlations between network density and the final score (rho =
      0.172) and negative correlations between network density and goals conceded (rho
      = - 0.300). Significant differences in the composite of centralities were found
      between positions (p = 0.001; ES = 0.293; moderate effect) and the location of
      the match (p = 0.001; ES = 0.013; no effect). This revealed that the general
      properties of cooperation increased with the competitive level, improved during
      the middle of the season and were better in home matches. Midfielders were most
      prominent players in elite and U19 teams in the mid-season and central defenders
      had the most prominent centralities in U17 and U15 during the early and late
      periods of the season.

PMID- 29599868
TI  - Strength and Conditioning Coaches' Application of the Session Rating of Perceived
      Exertion Method of Monitoring within Professional Rugby Union.
AB  - Session rating of perceived exertion (session-RPE) is a method of monitoring and
      managing training loads. The purpose of this study was to research how and for
      what purpose strength and conditioning (S&C) coaches implement this monitoring
      method within professional rugby union. The study also aimed to assess if S&C
      coaches found this monitoring method to be valid and effective. An online survey
      containing 24 fixed response questions was used to assess how S&C coaches applied
      the session-RPE method. The survey was piloted with expert researchers and
      practitioners in the area of session-RPE prior to distribution and alterations
      were made to the survey based on the experts' feedback. Twenty S&C coaches
      working with professional rugby union clubs in Ireland, England, Scotland and
      Wales completed the survey. The coaches' responses indicated that the majority
      found the session-RPE to be a valid and effective monitoring method. While some
      good implementation practices were identified, not all of the coaches adhered to
      these guidelines which may impact on the accuracy of the collected data. For
      example, 30% of coaches do not collect the RPE for every session that a player
      does per week limiting the use of the session-RPE variables cumulative training
      load, training monotony, training strain and acute:chronic load ratio. S&C
      coaches within rugby should consider using session-RPE as a method of monitoring
      and implement the method in a manner reflective of research findings to enhance
      the potential applications of this system in maximising adaptations and
      minimising the risk of injury.

PMID- 29599869
TI  - Variables that Predict Serve Efficacy in Elite Men's Volleyball with Different
      Quality of Opposition Sets.
AB  - The objective of this study was to determine the variables that predicted serve
      efficacy in elite men's volleyball, in sets with different quality of opposition.
      3292 serve actions were analysed, of which 2254 were carried out in high quality
      of opposition sets and 1038 actions were in low quality of opposition sets,
      corresponding to a total of 24 matches played during the Men's European
      Volleyball Championships held in 2011. The independent variables considered in
      this study were the serve zone, serve type, serving player, serve direction,
      reception zone, receiving player and reception type; the dependent variable was
      serve efficacy and the situational variable was quality of opposition sets. The
      variables that acted as predictors in both high and low quality of opposition
      sets were the serving player, reception zone and reception type. The serve type
      variable only acted as a predictor in high quality of opposition sets, while the
      serve zone variable only acted as a predictor in low quality of opposition sets.
      These results may provide important guidance in men's volleyball training
      processes.

PMID- 29599870
TI  - Effect of Two Different Types of Olympic Rotation Order on Cardiovascular and
      Metabolic Variables in Men's Artistic Gymnastics.
AB  - The rotation sequence-order differs from a gymnast to another according to the
      draw at the time of the qualifying competitions in men's artistic gymnastics.
      Only the six best gymnasts start on the floor exercises, the others could start
      on any of the other five apparatuses. It has been demonstrated that some
      gymnastics events are physiologically less taxing than others; hence some
      gymnasts could experience lower and/or higher levels of cardiovascular and
      metabolic stress compared to others, depending on the apparatus they start with.
      In this regard, the objective of this investigation was to compare cardiovascular
      and metabolic variables between two different types of Olympic rotation-order;
      one began with the floor exercises and the other began with the pommel horse. Six
      elite male gymnasts took part in this investigation. Heart rates, synchronized
      with real-time video acquisition, as well as capillary lactate concentration
      following each apparatus routine were monitored. Cardiovascular and metabolic
      stresses were significantly higher when gymnasts started their rotation with the
      pommel horse in all apparatuses except the pommel horse. The floor exercises'
      score was significantly affected when gymnasts ended up their competition on this
      apparatus. As a conclusion, starting gymnastics' competition on the floor
      exercises implicates less cardiovascular and metabolic stress associated with
      better performance compared with the other rotation order. As a matter of fact,
      best gymnasts who start on this apparatus could have a slight advantage compared
      with the other athletes.

PMID- 29599871
TI  - Effects of Different Post-Activation Potentiation Warm-Ups on Repeated Sprint
      Ability in Soccer Players from Different Competitive Levels.
AB  - This study aimed to compare the effects of a traditional warm-up with two post
      activation potentiation (PAP) warm-up strategies on the repeated sprint ability
      (RSA) of soccer players from national (NL) and regional (RL) competitive levels.
      Sixteen young players (NL, n = 8, age = 20.7 +/- 1.4 y, body mass = 68.5 +/- 7.0
      kg, body height = 177.4 +/- 5.2 cm; RL, n = 8, age = 20.8 +/- 1.0 y, body mass =
      68.7 +/- 4.0 kg, body height = 176.6 +/- 5.6 cm) were recruited to complete a
      traditional warm-up (CONTROL), a PAP warm-up incorporating squats with a load
      (~60% 1RM) that allowed a high speed (1 m/s) of movement and a high number of
      repetitions (PAP-1), and a PAP warm-up with a load (~90% 1RM) that allowed a
      moderate speed (0.5 m/s) of movement and a reduced number of repetitions (PAP
      0.5). A RSA test (six 20-m sprints with 20 s of recovery) was performed 5 min
      after the PAP warm-up to assess the effects of the different protocols on the
      fastest sprint (RSAb) and the mean time of all sprints (RSAm). A meaningful
      improvement of RSA performance was observed with PAP-0.5, attaining a large
      effect on NL (RSAb, ES = -1.5; RSAm, ES = -1.3) and only a small effect on RL
      athletes (RSAb and RSAm, ES = -0.2). Moreover, when each RSA sprint performance
      was compared between NL and RL players, after PAP-0.5 greater performance for all
      sprints was observed in the NL players. Therefore, adding a heavy strength-based
      conditioning exercise during the warm-up prior to a RSA test may induce
      significant performance improvements in NL, but only small effects in RL players.

PMID- 29599872
TI  - Responsiveness of the Countermovement Jump and Handgrip Strength to an
      Incremental Running Test in Endurance Athletes: Influence of Sex.
AB  - The present study analyzed the acute effects of an incremental running test on
      countermovement jump (CMJ) and handgrip strength performance in endurance
      athletes, considering the effect of post-exercise recovery time and sex. Thirty
      three recreationally trained long-distance runners, 20 men and 13 women,
      participated voluntarily in this study. The participants performed the Leger
      test, moreover, the CMJ and handgrip strength tests were carried out before and
      after the running test and during different stages of recovery (at the 1st min of
      recovery (posttest1), 5th min of recovery (posttest2), and 10th min of recovery
      (posttest3)). Two-way analysis of variance revealed a significant improvement in
      the CMJ (pre-posttest1, p = 0.001) and handgrip strength (pre-posttest2, p =
      0.017) during recovery time. The Pearson's Chi-2 test showed no significant
      relationship (p >= 0.05) between sex and post-activation potentiation (PAP). A
      linear regression analysis pointed to heart rate recovery as a predictive factor
      of CMJ improvement (PAP). In conclusion, despite significant fatigue reached
      during the Leger test, the long-distance runners did not experience an impaired
      CMJ and handgrip strength performance, either men or women, achieving an
      improvement (PAP) in posttest conditions. The results obtained showed no
      significant relationship between sex and PAP. Moreover, significant effect of
      recovery after running at high intensity on CMJ performance and handgrip strength
      was found. Finally, the data suggest that PAP condition can be predicted by heart
      rate recovery in endurance runners.

PMID- 29599873
TI  - Physical Performance Comparison between Under 15 Elite and Sub-Elite Soccer
      Players.
AB  - The aim of this study was to compare the physical performance profile among young
      soccer players of different competitive levels. Two teams of elite (n = 22) and
      sub-elite (n = 22) soccer players at national (highly skilled) and regional
      (moderately skilled) level were recruited in the study. All participants were
      tested using a modified Illinois change of direction speed test, a T-drill with
      and without a ball, a countermovement jump, and a 10-m sprint. The analysis
      revealed significant differences in favor of elite players in sprint (d = 1.54,
      large) and vertical jump (d = 2.03, very large) outcomes, while no differences
      were observed in both modified Illinois change of direction speed (d = 0.16,
      trivial) and T-drill (d = 0.20, small) tests between the groups. The ability to
      change direction and speed with and without a ball was found not to be suitable
      enough to highlight the difference among youth players with moderate-to-high
      level of play. In conclusion, multi-testing approach based on task-related power
      should include vertical jump and sprint performance to delineate players of a
      higher level.

PMID- 29599874
TI  - Validation and Reliability of the Korean Version of the Sport Anxiety Scale-2.
AB  - The main purpose of the present study was to examine the validation and
      reliability of the Korean version of the Sport Anxiety Scale (SAS-2Kr) by
      evaluating its factorial invariance across gender. A total of 303 Korean
      collegiate athletes (198 males and 105 females) from 9 sports participated in the
      study, and they completed the demographic questionnaire and the SAS-2Kr
      containing 15 items to measure multidimensional trait anxiety and individual
      differences in the cognitive and somatic anxiety experienced by athletes. The
      results of this study indicated that the construct validity in the SAS-2Kr was
      well established in that the values of the standardized factor loadings,
      composite reliability, and average variance extracted values were above the
      recommended cutoff points. The multiple-sample confirmatory factor analyses
      showed the SAS-2Kr could be generalizable across gender in college samples. The
      results also indicated that the SAS-2Kr supported the original 3-factor model of
      SAS-2 in English consisting of somatic anxiety, worry, and concentration
      disruption, and thus this study provides useful information for researchers to
      understand the athletes' tendency to experience anxiety reactions in sport
      situations. Suggestions for future research on competitive trait anxiety are
      provided in the discussion section.

PMID- 29599875
TI  - Analysis of Tactical, Decisional and Executional Behaviour according to the Level
      of Expertise in Squash.
AB  - The objective of this study was to analyse the differences in tactical
      principles, decision-making and execution of the return shot and drop shot of
      squash players at different levels of proficiency. The sample was composed of 80
      players, divided into four levels of expertise (first national category, second
      national category, autonomous regional level and provincial level). The Squash
      Performance Evaluation Tool was used for recording the level of decision-making
      and execution. The results revealed that reading of the context of the game
      improved as the level of the player's expertise of both the return shot and the
      drop shot increased. The correlation between correct decision-making and better
      quality execution for both the return shot and the drop shot in squash also
      improved with the player's level of expertise. According to these results,
      improvements in situational tactical principles and the application of tactical
      principles, correct decision-making and high-quality execution are essential to
      develop the athletic performance level among squash players.

PMID- 29599876
TI  - Competition Field Perceptions of Table-tennis Athletes and their Performance.
AB  - The distinction between positive and negative perceptions is fundamental in
      perception models. The purpose of this study was to investigate the correlation
      between field perceptions of table tennis players and the outcome (net result)
      during the matches in a competition. Experimental data were collected from 10
      elite table tennis players and analysed. The results addressed the following
      three competition field perceptions: (1) before the service, the player's
      positive perceptions had significant effect on the positive outcome (winning
      rate) of that service; (2) the perception after the net result of the previous
      service increased the positive outcome of the next service, and (3) the player's
      positive/negative perception during the matches affected the win/loss outcome of
      that competition. In conclusion, the player's positive perceptions enhanced their
      winning rate during table tennis competitions. Therefore, during the training
      program, coaches need to develop positive perceptions and strengthen the
      psychological quality of table tennis players.

PMID- 29599877
TI  - Motivational Climate Sport Youth Scale: Measurement Invariance Across Gender and
      Five Different Sports.
AB  - The aim of this study was to analyze the psychometric properties of the
      Portuguese version of the Motivational Climate Sport Youth Scale (MCSYSp) and
      invariance across gender and different sports (swimming, soccer, handball,
      basketball, futsal). A total of 4,569 athletes (3,053 males, 1,516 females) from
      soccer (1,098), swimming (1,049), basketball (1,754), futsal (340), and handball
      (328) participated in this study, with ages between 10 and 20 years (M = 15.13;
      SD = 1.95). The results show that the original model (two factors/12 items) did
      not adjust to the data in a satisfactory way; therefore, it was necessary to
      change the model by removing four items (two from each factor). Subsequently, the
      model adjusted to the data in a satisfactory way (chi2 = 499.84; df = 19; chi2/df
      = 26.30; p < .001; SRMR = .037; TLI = .923; CFI = .948; RMSEA = .074; IC90% .069
      .080) and was invariant by gender and team sports (soccer, handball, basketball,
      futsal) (DeltaCFK<=.01); however, it was not invariant between swimming and team
      sports (soccer, handball, basketball, futsal) (DeltaCFI >= .01). In conclusion,
      the MCSYSp (two factors/eight items) is a valid and reliable choice that is
      transversal not only to gender, but also to the different studied team sports to
      measure the perception of the motivational climate in athletes. Future studies
      can research more deeply the invariance analysis between individual sports to
      better understand the invariance of the model between individual and team sports.

PMID- 29599878
TI  - Understanding Trail Runners' Activity on Online Community Forums: An Inductive
      Analysis of Discussion Topics.
AB  - Recreational trail runners often participate in online community forums where
      they can freely read posted messages, join discussions and/or introduce new
      discussion topics. This tool can enhance learning as runners connect with other
      trail runners and reflect on how they can better organize their own practice.
      Studying forum activity would provide greater insight into the relationship
      between field practice and dedicated forums. The aim of this study was therefore
      to detect the topics discussed online by trail runners in order to understand how
      they collectively look for solutions that help them adapt to issues that emerge
      during actual practice. The discussion topics (n = 171) on the forum hosted by
      the Raidlight brand were examined using inductive content analysis, which
      distinguished two general dimensions. The first dimension was training and had
      four first-order themes (i.e., "specific trail running sessions", "complementary
      trail running sessions". "training plans" and "specific questions about races")
      grouped into two second-order themes (i.e., "training session contents" and
      "structure and schedule"). The second dimension was health and had seven first
      order themes (i.e., "tendinitis", "muscle issues", "foot issues", "sprains and
      fractures", "pain", "physiology" and "substances and practitioners") grouped into
      two second-order themes (i.e., "pain and injury" and "prevention"). The results
      indicate that the issues that trail runners discuss on forums are significant and
      that the successions of questions and solutions are a fruitful means for
      building, enriching and adjusting their activity as they cope with constraints.
      As a practical consequence, suggestions for improving such online platforms are
      made.

PMID- 29599879
TI  - A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an
      African oral pathology research consortium initiative.
AB  - Introduction: Oral cancer is a leading cause of cancer deaths among African
      populations. Lack of standard cancer registries and under-reporting has
      inaccurately depicted its magnitude in Nigeria. Development of multi-centre
      collaborative oral pathology networks such as the African Oral Pathology Research
      Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust
      and systematic investigation of oral diseases across Africa. Methods: In this
      descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to
      examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data
      from 4 major tertiary health institutions in Western and Southern Nigeria was
      generated using a standardized data extraction format and analysed using the SPSS
      data analysis software (version 20.0; SPSS Inc. Chicago, IL). Results: Of the 162
      cases examined across the 4 centres, we observed that oral squamous cell
      carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and
      maxillary were more frequent than mandibular OSCC lesions. Regional variations
      were observed both for location, age group and gender distribution. Significant
      regional differences was found between poorly, moderately and well differentiated
      OSCC (p value = 0.0071). Conclusion: A multi-centre collaborative oral pathology
      research approach is an effective way to achieve better insight into the patterns
      and distribution of various oral diseases in men of African descent. The wider
      outlook for AOPRC is to employ similar approaches to drive intensive oral
      pathology research targeted at addressing the current morbidity and mortality of
      various oral diseases across Africa.

PMID- 29599880
TI  - ?
AB  - Neonatal thrombopenia is the most common hemostatic abnormality in newborns. It
      is defined as a platelet count below 150.000/mm3. 40% of newborns to mothers with
      a history of autoimmune thrombopenia are at risk of developing neonatal
      thrombopenia while 10-15% of them are at risk of developing severe thrombopenia.
      We here report the case of a 20 days old newborn to mother splenectomized for
      idiopathic thrombopenic purpura in order to highlight the relationship between
      the severity of maternal disease and the severity of the neonatal thrombopenia
      and thereby to avoid the risk of intracranial hemorrhage resulting in death or
      neurological sequelae.

PMID- 29599881
TI  - [Breast tuberculosis: about a case].
AB  - Breast tuberculosis is rare. It poses a problem of differential diagnosis because
      it may be mistaken for breast cancer as clinical examination and diagnostic
      imaging are not specific. Breast tuberculosis should be suspected especially in
      endemic countries or in immunosuppressed individuals. We report the case of a
      menopausal woman with breast tuberculosis in order to raise concern for
      diagnosis.

PMID- 29599882
TI  - Unusual cause of abdominal pain: the disconnected tube after laparoscopic
      adjustable gastric banding.

PMID- 29599883
TI  - [Overview of X-linked adrenoleukodystrophy in Morocco: results of the
      implementation of the program of clinical and biological diagnosis].
AB  - Introduction: X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative
      disease, due to mutations in the ABCD1 gene. It manifests as a damage to the
      central and peripheral nervous system, adrenal insufficiency and testicular
      damage in children. Diagnosis is based on the determination of long-chain
      saturated fatty acids. Early diagnosis is essential because it defines treatment
      accessibility according to disease stage. Methods: We implemented a X-ALD
      diagnostic test program in Morocco at the Children's Hospital and at the Central
      Laboratory for inherited and metabolic diseases in Rabat. The program was based
      around three priorities, namely: the recruitment of patients, diagnosis and
      awareness. Diagnosis is based on three protocols: a protocol for symptomatic
      cases, a protocol for asymptomatic cases and a protocol for heterozygous women.
      Results: During the first three years after implementation of our X-ALD
      diagnostic test program, we diagnosed the disease in seven families, with nine
      boys and three heterozygous women. All children were diagnosed with demyelinating
      brain. All heterozygous women were asymptomatic. Different symptom-based
      therapies were established. Conclusion: X-ALD is a rare disease. Our diagnostic
      program has helped to diagnose a significant number of cases, hence its
      importance. Campaigns focused on raising awareness among health care
      professionals will enable a better understanding of the disease and a more
      accurate diagnosis as well as to improve access to health care for a higher
      number of patients.

PMID- 29599884
TI  - Prevalence of chronic viral hepatitis infections in Karaj, Iran.
AB  - Introduction: Viral hepatitis is challenging for health and blood safety. Studies
      carried out on blood donors can help find the frequency and trending of hepatitis
      B and C infections in a community and also safety of donation. The study aim is
      to determine the prevalence of HBV and HCV in Karaj blood donors over a four year
      period between 2010 to 2013. Methods: This study reports the results of a cross
      sectional seroepidemiological study of hepatitis B and C in blood donors. Data on
      hepatitis infection and demographic characteristics of donors were gathered from
      blood donor registries. Frequency of hepatitis infections were described with 95%
      confidence interval. Chi square and logistic regression were used for analysis.
      Results: The frequency of HBV and HCV infection in Karaj blood donors was 0.40%
      and 0.18% respectively. In first time donors, HBV and HCV positivity risk was
      respectively 3.59 and 4.8 fold in people with primary education (OR=3.59; 95% CI
      between 2.68-4.80) comparing to academic level. Frequency of hepatitis B has
      decreased significantly (P<0.001) during study period but frequency of Hepatitis
      C has not changed significantly. Conclusion: The frequencies of HBV and HCV
      infection in Karaj blood donor population is low. There are equal infection rates
      within both genders. This must be considered in controlling transmission of
      infection in this area.

PMID- 29599885
TI  - [Narrow lumbar channel due to epidural lipomatosis: case report and literature
      review].
AB  - Epidural lipomatosis is characterized by the abnormal accumulation of non
      encapsulated grease in the epidural space. Although rare, it is a possible cause
      of lombosciatica or narrow lumbar channel. It is often associated with
      contributing factors such as prolonged corticosteroid therapy or obesity. We
      report the case of a patient presenting with disabling lombosciatalgias.
      Radiological evaluation confirmed the diagnosis of compressive epidural
      lipomatosis. Patient's evolution was favorable after surgical decompression.

PMID- 29599886
TI  - [Malignant transformation of chronic osteomyelitis: a case report].
AB  - Malignant transformation of chronic osteomyelitis is a rare and late complication
      which mainly occurs at the level of the edges of a fistulous tract with extension
      and infiltration to the surrounding soft tissues and more rarely to bones. We
      here report the case of Mr N.J. aged 67 years, followed up for chronic
      osteomyelitis of the right femur fistulized to the skin and evolving since the
      age of 16 years. He presented with secerning fistulas. Imaging examination showed
      pathologic fracture due to osteolytic lesion of the lower extremity of the right
      femur associated with poorly defined intra-medullary collection of fluid
      measuring 8 cm along its longer axis. The patient underwent surgical resection of
      the fistulas with complete evacuation and curettage of the bone cavity.
      Pathological examination showed differentiated keratinising squamous cell
      carcinoma, infiltrating the fistulous tract and extending to the soft parts and
      to the lower extremity of the right femur. Staging was negative. Disarticulation
      of the HIP was performed. At two-years follow-up the patient was doing well
      without local recurrence or distant metastasis. Initial treatment of chronic
      osteomyelitis is essential to prevent alarming complications. Amputation is the
      treatment of choice in patients with malignant transformation of chronic
      osteomyelitis in particular to squamous cell carcinoma, as in the case of our
      patient, in order to to prevent secondary involvement.

PMID- 29599887
TI  - [Pepper's syndrome: report of two cases at the Charles de Gaulle University
      Pediatric Hospital Center, Ouagadougou (Burkina Faso)].
AB  - Pepper's syndrome is a neuroblastoma that metastasizes to the liver. It affects
      infants younger than six months of age. It can regress spontaneously and is
      associated with a favorable prognosis in 80% of cases. Given its rarity, we here
      report two cases of Pepper's syndrome observed at the Charles de Gaulle
      university pediatric hospital center, Ouagadougou (Burkina Faso). Our study
      involved two female infants in whom the disease manifested as an increase in
      abdominal volume, hepatomegaly and signs of respiratory distress. Ultrasound
      enabled diagnosis, which was based on the nodular appearance of the liver in both
      cases and determination of the primary tumor in one case. Urinary catecholamine
      test confirmed the diagnosis in one case. Both patients died from complications
      related to liver compression, chemotherapy (in one of the cases) and lack of
      treatment (in the other case).

PMID- 29599888
TI  - [Aggressive renal angiomyolipoma extending to the renal vein: about a case and
      literature review].
AB  - Renal angiomyolipoma is a benign tumor. It is characterized of three different
      components: muscular, vascular and greasy. Their distribution is variable.
      Diagnosis is based on the identification of the intratumoral greasy component on
      CT scan and MRI. In exceptional circumstances, this tumor may be aggressive with
      locoregional and venous extension (renal vein and inferior vena cava). We here
      report the case of a 37-year old patient with voluminous renal angiomyolipoma
      extending to the renal vein.

PMID- 29599889
TI  - Evolution of HIV prevalence and behavioral factors among MSM in Togo between 2011
      and 2015.
AB  - Introduction: The aim of this study was to assess sexual behavior and measure HIV
      prevalence among MSM in 2015, in Togo. Methods: We conducted a cross-sectional
      study from February to March 2015 in nine major cities of Togo. The respondent
      driven sampling method was used to recruit MSM. Behavioral data were collected by
      interviewer-administered questionnaires. The blood tests were then carried out
      among MSM to assess their HIV status. Data were inputted into an Epidata database
      and exported to STATA(r) 9.0 for analysis. Qualitative variables were compared
      using the chi-2. Results: A total of 496 MSM were involved in this study, with
      43.35% in the capital, Lome. Over the past 12 months, 88.9% of MSM had had sexual
      intercourse with men and 24.1% of them had had sex with women. The last sexual
      intercourse was with a casual partner among 52.9% of MSM. During the last 30 days
      preceding the survey, 68.5% of MSM had regularly used a condom during active anal
      intercourse and 71.9% had used it during passive anal intercourse. The national
      prevalence rate of HIV among MSM was 13.0%. The factors associated with HIV
      infection were age of MSM OR = 5.30 [1.85-15.1], HIV testing history OR = 2.63
      [1.18-5.87] and the city of residence of MSM OR = 5.56 [2.90-10.64]. Conclusion:
      This study confirms that HIV prevalence among MSM is five times higher than in
      the general population (13% vs 2.5%). Thus, the need to rethink HIV sensitization
      and prevention strategies targeting hidden and stigmatized populations such as
      MSM.

PMID- 29599890
TI  - [Moya moya disease: a rare cause of ischemic stroke in children: about a case].
AB  - Moya moya disease is an angiogenic disease characterized by the narrowing of the
      distal internal carotid artery extending to the proximal segments of the middle
      and anterior cerebral arteries, inducing collateral vessels formation. These
      vessels come from the collateral parenchymal vessels, the perforating vessels,
      leptomeningeal vessels and other transdural anastomoses. These collateral vessels
      have a characteristic appearance on angiography, forming a cloud of smoke: net
      like moyamoya. Its etiology is still poorly understood. Moyamoya disease accounts
      for 10-15% of the causes of stroke, with 2 age peaks at which its occurrence is
      more frequent: children around 5 years old and adults around 40 years old. Its
      evolution can be slow with intermittent symptoms or fulminant with fast
      neurological deterioration. The current data show the role of surgery as the gold
      standard for the treatment of moyamoya syndrome, in particular in patients with
      progressive and recurrent symptoms.

PMID- 29599891
TI  - [Alobar holoprosencephaly associated with diabetes insipidus and hypothyroidism
      in a 10-month old infant].
AB  - Holoprosencephaly (HPE) is a serious brain malformation due to a failure of
      medial forebrain cleavage. This is an abnormality which is more often associated
      with craniofacial malformations, psychomotor development delay, diabetes
      insipidus and variable endocrine disorders. It is due to different causes
      including chromosomal abnormalities (trisomy 13, 18)and polymalformative
      syndromes (CHARGE Syndrome). Diagnosis is based on brain imaging. A few rare
      cases have been described in the literature. We here report the case of alobar
      HPE in a 10-month old infant. Diagnosis was based on cerebral CT scan performed
      due to delayed psychomotor development and in the absence of visible
      malformations. Endocrine assessment allowed to detect central diabetes insipidus
      and central hypothyroidism, probably of hypothalamic origin.

PMID- 29599892
TI  - Thioredoxin-1 Protects Bone Marrow-Derived Mesenchymal Stromal Cells from
      Hyperoxia-Induced Injury In Vitro.
AB  - Background: The poor survival rate of mesenchymal stromal cells (MSC)
      transplanted into recipient lungs greatly limits their therapeutic efficacy for
      diseases like bronchopulmonary dysplasia (BPD). The aim of this study is to
      evaluate the effect of thioredoxin-1 (Trx-1) overexpression on improving the
      potential for bone marrow-derived mesenchymal stromal cells (BMSCs) to confer
      resistance against hyperoxia-induced cell injury. Methods: 80% O2 was used to
      imitate the microenvironment surrounding-transplanted cells in the hyperoxia
      induced lung injury in vitro. BMSC proliferation and apoptotic rates and the
      levels of reactive oxygen species (ROS) were measured. The effects of Trx-1
      overexpression on the level of antioxidants and growth factors were investigated.
      We also investigated the activation of apoptosis-regulating kinase-1 (ASK1) and
      p38 mitogen-activated protein kinases (MAPK). Result: Trx-1 overexpression
      significantly reduced hyperoxia-induced BMSC apoptosis and increased cell
      proliferation. We demonstrated that Trx-1 overexpression upregulated the levels
      of superoxide dismutase and glutathione peroxidase as well as downregulated the
      production of ROS. Furthermore, we illustrated that Trx-1 protected BMSCs against
      hyperoxic injury via decreasing the ASK1/P38 MAPK activation rate. Conclusion:
      These results demonstrate that Trx-1 overexpression improved the ability of BMSCs
      to counteract hyperoxia-induced injury, thus increasing their potential to treat
      hyperoxia-induced lung diseases such as BPD.

PMID- 29599893
TI  - Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and
      Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui
      Bogam.
AB  - Aim: Although stroke is among the leading causes of death and long-term
      disability, there are few effective treatments for limiting the severity of
      neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in
      the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke
      symptoms in a mouse model of cerebral ischemia. Methods: Focal cerebral ischemia
      was induced via photothrombosis. Infarct volume, brain edema, and neurological
      deficits were evaluated. Immunofluorescence staining for tight junction proteins
      and aquaporin 4 (AQP4) was performed following ischemic injury. Results: Based on
      our initial findings, we examined the effects of two prescriptions in which the
      candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and
      Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct
      volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and
      improved neurological and motor functions in a dose-dependent manner (30, 100,
      and 300 mg/kg), while no such effects were observed in mice pretreated with
      Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in
      ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang
      pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions: These
      results indicate that Shuanghe-tang may protect against brain injury and promote
      recovery of neurological function following ischemia.

PMID- 29599895
TI  - Corrigendum to "Cytoprotective and Cytotoxic Effects of Rice Bran Extracts in Rat
      H9c2(2-1) Cardiomyocytes".
AB  - [This corrects the article DOI: 10.1155/2016/6943053.].

PMID- 29599896
TI  - Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in
      the Mouse Air Pouch.
AB  - Heme oxygenase-1 (HO-1) is induced by many stimuli to modulate the activation and
      function of different cell types during innate immune responses. Although HO-1
      has shown anti-inflammatory effects in different systems, there are few data on
      the contribution of myeloid HO-1 and its role in inflammatory processes is not
      well understood. To address this point, we have used HO-1M-KO mice with myeloid
      restricted deletion of HO-1 to specifically investigate its influence on the
      acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we
      have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil
      infiltration accompanied by high levels of inflammatory mediators such as
      interleukin-1beta, tumor necrosis factor-alpha, and prostaglandin E2. The
      expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3) was also
      enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice
      compared with control mice, suggesting the presence of systemic inflammation.
      Altogether, these findings demonstrate that myeloid HO-1 plays an anti
      inflammatory role in the acute response to zymosan in vivo and suggest the
      interest of this target to regulate inflammatory processes.

PMID- 29599894
TI  - Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest,
      Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis.
AB  - The prevalence of Osteoarthritis (OA) is increasing because of the progressive
      aging and unhealthy lifestyle. These risk factors trigger OA by removing
      constraints that keep the tightly regulated low turnover of the extracellular
      matrix (ECM) of articular cartilage, the correct chondrocyte phenotype, and the
      functionality of major homeostatic mechanisms, such as mitophagy, that allows for
      the clearance of dysfunctional mitochondria, preventing increased production of
      reactive oxygen species, oxidative stress, and senescence. After OA onset, the
      presence of ECM degradation products is perceived as a "danger" signal by the
      chondrocytes and the synovial macrophages that release alarmins with
      autocrine/paracrine effects on the same cells. Alarmins trigger innate immunity
      in the joint, with important systemic crosstalks that explain the beneficial
      effects of dietary interventions and improved lifestyle. Alarmins also boost low
      grade inflammation: the release of inflammatory molecules and chemokines
      sustained by continuous triggering of NF-kappaB within an altered cellular
      setting that allows its higher transcriptional activity. Chemokines exert
      pleiotropic functions in OA, including the recruitment of inflammatory cells and
      the induction of ECM remodeling. Some chemokines have been successfully targeted
      to attenuate structural damage or pain in OA animal models. This represents a
      promising strategy for the future management of human OA.

PMID- 29599897
TI  - Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease.
AB  - Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and
      emphysema. Environmental exposure, primarily cigarette smoking, can cause high
      oxidative stress and is the main factor of COPD development. Cigarette smoke also
      contributes to the imbalance of oxidant/antioxidant due to exogenous reactive
      oxygen species (ROS). Moreover, endogenously released ROS during the inflammatory
      process and mitochondrial dysfunction may contribute to this disease progression.
      ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such
      as DNA, proteins, and lipids leading to epithelial cell injury and death. Various
      detoxifying enzymes and antioxidant defense systems can be involved in ROS
      removal. In this review, we summarize the main findings regarding the biological
      role of ROS, which may contribute to COPD development, and cytoprotective
      mechanisms against this disease progression.

PMID- 29599898
TI  - The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the
      Activity of Antioxidant Enzymes.
AB  - Ibogaine is an indole alkaloid originally extracted from the root bark of the
      African rainforest shrub Tabernanthe iboga. It has been explored as a treatment
      for substance abuse because it interrupts drug addiction and relieves withdrawal
      symptoms. However, it has been shown that ibogaine treatment leads to a sharp and
      transient fall in cellular ATP level followed by an increase of cellular
      respiration and ROS production. Since contractile tissues are sensitive to
      changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated
      link between altered redox homeostasis and uterine contractile activity. We found
      that low concentrations of ibogaine stimulated contractile activity in
      spontaneously active uteri, but incremental increase of doses inhibited it.
      Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px
      activity, but doses that completely inhibited contractions increased CAT
      activity. Western blot analyses showed that changes in enzyme activities were not
      due to elevated enzyme protein concentrations but posttranslational
      modifications. Changes in antioxidant enzyme activities point to a vast
      concentration-dependent increase in H2O2 level. Knowing that extracellular ATP
      stimulates isolated uterus contractility, while H2O2 has an inhibitory effect,
      this concentration-dependent stimulation/inhibition could be linked to ibogaine
      related alterations in ATP level and redox homeostasis.

PMID- 29599900
TI  - Metabolomics: From liver chiromancy to personalized precision medicine in
      advanced chronic liver disease.
AB  - Currently there is a lack of accurate biomarkers for diagnosis and prognosis in
      advanced liver diseases. Either the occurrence of first decompensation, or
      diagnosis of acute on chronic liver failure, severe alcoholic hepatitis, or
      hepatocellular carcinoma (HCC), none of the available biomarkers are
      satisfactory. Metabolomics is the newest of omics, being much closer than the
      others to the actual phenotype and pathologic changes that characterizes a
      certain condition. It deals with a much wider spectrum of low molecular weight
      bio-compounds providing a powerful platform for discovering novel biomarkers and
      biochemical pathways to improve diagnostic, prognostication and therapy. Until
      now metabolomics was applied in a wide spectrum of liver conditions, but the
      findings were contradictory. This review proposes a synthesis of the existing
      evidences of metabolomics use in advanced chronic liver diseases, decompensated
      liver cirrhosis, severe alcoholic hepatitis and HCC.

PMID- 29599899
TI  - Reactivation of hepatitis B after liver transplantation: Current knowledge,
      molecular mechanisms and implications in management.
AB  - Chronic hepatitis B (CHB) is a major global health problem affecting an estimated
      350 million people with more than 786000 individuals dying annually due to
      complications, such as cirrhosis, liver failure and hepatocellular carcinoma
      (HCC). Liver transplantation (LT) is considered gold standard for treatment of
      hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant
      viral reactivation can be detrimental to allograft function, leading to poor
      survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti
      viral drugs have achieved remarkable progress in LT by suppressing viral
      replication and improving long-term survival. The combination of lamivudine (LAM)
      plus HBIG has been for many years the most widely used. However, life-long HBIG
      use is both cumbersome and costly, whereas long-term use of LAM results in
      resistant virus. Recently, in an effort to develop HBIG-free protocols, high
      potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried
      either as monotherapy or in combination with low-dose HBIG with excellent
      results. Current focus is on novel antiviral targets, especially for covalently
      closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of
      viral suppression. However, there are several other molecular mechanisms through
      which HBV may reactivate and need equal attention. The purpose of this review is
      to address post-LT HBV reactivation, its risk factors, underlying molecular
      mechanisms, and recent advancements and future of anti-viral therapy.

PMID- 29599901
TI  - Management of restless legs syndrome in chronic liver disease: A challenge for
      the correct diagnosis and therapy.
AB  - AIM: To investigate the association between restless legs syndrome (RLS) and well
      defined chronic liver disease, and the possible therapeutic options. METHODS: Two
      hundred and eleven patients with chronic liver disease, complaining of sleep
      disturbances, painful leg sensation and daily sleepiness, were included. Patients
      with persistent alcohol intake, recent worsening of clinical conditions, or
      hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns
      Hopkins questionnaire and verified by fulfilling the diagnostic criteria by
      Allen. All patients were tested, both at baseline and during follow-up, with the
      Hamilton rating scale for depression, sleep quality assessment (PSQI), Epworth
      sleepiness scale (ESS), International Restless Legs Syndrome Study Group
      evaluation, and international RLS severity (IRLS) scoring system. Iron-free
      level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological
      examinations and blood test occurred at the beginning of the therapy, after 2 wk,
      and at the 28th, 75th, 105th, 135th, 165th and 205th day. Regarding therapy,
      pramipexole or gabapentin were used. RESULTS: Patients were moderately depressed,
      with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep
      problems and involuntary leg movements had been underestimated, and RLS syndrome
      had not been considered before the neurological visit. All (211/211) patients
      fulfilled the RLS diagnostic criteria. Twenty-two patients considered their
      symptoms as mild, according to IRSL, but 189 found them moderate to very severe.
      No correlation was found between ammonium level and ESS or PSQI. Augmentation was
      rather precocious in our patients (135th day), and more frequent (35%) than
      previous data (8.3%-9.1%). The dosage of dopamine agonists was found to be
      associated with augmentation and appears in range with the literature. Previous
      intake of alcohol and lower levels of vitamins have been related to the
      phenomenon in our study. CONCLUSION: RLS is a common disorder, requiring rapid
      diagnosis and treatment. Further research is therefore fundamental.

PMID- 29599902
TI  - Clostridium paraputrificum septicemia and liver abscess.
AB  - We report the first case of a healthy 23-year-old female who underwent an
      interventional radiology-guided embolization of a hepatic adenoma, which resulted
      in a gas forming hepatic liver abscess and septicemia by Clostridium
      paraputrificum. A retrospective review of Clostridial liver abscesses was
      performed using a PubMed literature search, and we found 57 clostridial hepatic
      abscess cases. The two most commonly reported clostridial species are C.
      perfringens and C. septicum (64.9% and 17.5% respectively). C. perfringens cases
      carried a mortality of 67.6% with median survival of 11 h, and 70.2% of the C.
      perfringens cases experienced hemolysis. All C. septicum cases were found to have
      underlying liver malignancy at the time of the presentation with a mortality of
      only 30%. The remaining cases were caused by various Clostridium species, and
      this cohort's clinical course was significantly milder when compared to the above
      C. perfringens and C. septicum cohorts.

PMID- 29599903
TI  - Liver failure caused by prolonged state of malnutrition following bariatric
      surgery.
AB  - Bariatric surgery is an effective tool in the treatment of patients with morbid
      obesity. In these case reports we describe 2 patients who developed liver failure
      after currently-practiced types of bariatric surgery, caused by a prolonged state
      of malnutrition provoked by psychiatric problems. Despite intensive guidance of a
      psychologist and dieticians after surgery, our patients deteriorated
      psychologically, resulting in a prolonged state of severe malnutrition and
      anorexia. Finally, a state of starvation was reached, passing a critical level of
      the liver capacity. Patients who present with signs of severe protein
      malnutrition after bariatric surgery should be closely monitored and checked for
      nutritional status. Specific attention should be given to patients who develop
      psychiatric problems post-bariatric surgery. If refeeding does not result in
      clinical improvement, reversal surgery should be considered in a timely manner.

PMID- 29599904
TI  - Targeting multidrug-resistant ovarian cancer through estrogen receptor alpha
      dependent ATP depletion caused by hyperactivation of the unfolded protein
      response.
AB  - Ovarian cancers often recur and tumors acquire resistance to chemotherapy due to
      overexpression of the ATP-dependent efflux pump, multidrug resistance protein 1
      (MDR1/P-glycoprotein/ABCB1). Nontoxic small molecule inhibitors targeting MDR1
      have remained largely elusive. Instead, in a novel application of our recently
      described estrogen receptor alpha (ERalpha) biomodulator, BHPI, we targeted
      MDR1's substrate, ATP. BHPI depletes intracellular ATP and nearly blocks MDR1
      mediated drug efflux in ovarian cancer cells by inducing toxic hyperactivation of
      the endoplasmic reticulum stress sensor, the unfolded protein response (UPR).
      BHPI increased sensitivity of MDR1 overexpressing multidrug resistant OVCAR-3
      ovarian cancer cells to killing by paclitaxel by >1,000 fold. BHPI also restored
      doxorubicin sensitivity in OVCAR-3 cells and in MDR1 overexpressing breast cancer
      cells. In an orthotopic OVCAR-3 xenograft model, paclitaxel was ineffective and
      the paclitaxel-treated group was uniquely prone to form large secondary tumors in
      adjacent tissue. BHPI alone strongly reduced tumor growth. Notably, tumors were
      undetectable in mice treated with BHPI plus paclitaxel. Compared to control
      ovarian tumors, after the combination therapy, levels of the plasma ovarian
      cancer biomarker CA125 were at least several hundred folds lower; moreover, CA125
      levels progressively declined to undetectable. Targeting MDR1 through UPR
      dependent ATP depletion represents a promising therapeutic strategy.

PMID- 29599905
TI  - Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian
      neoplasms in Japanese patients.
AB  - Aim: Endometriosis-related ovarian neoplasms (ERONs) have recently attracted
      considerable attention; however, the prevalence and patterns of ARID1A and POLE
      mutations in ERONs have not been studied in detail. The aim of this study was to
      investigate not only the carcinogenesis of ERONs, but also the prognostic
      significance of several gene mutations in this cohort. We used DNA purified from
      only tumor epithelial cells, from which fibroblasts were removed, using a
      specific method we called "liquid microdissection". Methods: Tissue samples from
      22 ovarian carcinomas (13 endometrioid, and nine clear cell) were used. Tumor
      cells were isolated using a cell sorting system and DNA was purified from tumor
      epithelial cells. Nucleotide sequencing was conducted to analyze the mutational
      status of ARID1A, p53, PTEN, POLE, PIK3CA, and KRAS. Results: In ERONs, the
      frequencies of somatic mutations in ARID1A, p53, POLE, PTEN, PIK3CA, and KRAS
      were 19/20 (95.0%), 7/19 (36.8%), 9/22 (40.9%), 13/19 (68.4%), 3/19 (15.8%), and
      1/9 (11.1%). The frequency of ARID1A mutations was significantly higher than that
      reported previously. Kaplan-Meier survival analysis revealed that mutations in
      all genes, including POLE, were not associated with patient prognosis in our
      Japanese cohort. Conclusions: Our results suggest that the frequency of ARID1A
      mutations in ERONs may be higher than that previously reported. In addition, the
      "liquid microdissection" method that we chose for DNA purification could be used
      to obtain high-quality sequencing results. The findings suggest that ARID1A
      mutations represent the basis of ERON carcinogenesis; other subsequent gene
      mutations may result in the progression of carcinogenesis.

PMID- 29599906
TI  - Dynamic changes during the treatment of pancreatic cancer.
AB  - This manuscript follows a single patient with pancreatic adenocarcinoma for a
      five year period, detailing the clinical record, pathology, the dynamic evolution
      of molecular and cellular alterations as well as the responses to treatments with
      chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from
      biopsies and blood identified a dynamic set of changes in allelic imbalances and
      copy number variations in response to therapies. Organoid cultures established
      from biopsies over time were employed for extensive drug testing to determine if
      this approach was feasible for treatments. When an unusual drug response was
      detected, an extensive RNA sequencing analysis was employed to establish novel
      mechanisms of action of this drug. Organoid cell cultures were employed to
      identify possible antigens associated with the tumor and the patient's T-cells
      were expanded against one of these antigens. Similar and identical T-cell
      receptor sequences were observed in the initial biopsy and the expanded T-cell
      population. Immunotherapy treatment failed to shrink the tumor, which had
      undergone an epithelial to mesenchymal transition prior to therapy. A warm
      autopsy of the metastatic lung tumor permitted an extensive analysis of tumor
      heterogeneity over five years of treatment and surgery. This detailed analysis of
      the clinical descriptions, imaging, pathology, molecular and cellular evolution
      of the tumors, treatments, and responses to chemotherapy, targeted therapies, and
      immunotherapies, as well as attempts at the development of personalized medical
      treatments for a single patient should provide a valuable guide to future
      directions in cancer treatment.

PMID- 29599907
TI  - Epidrug-induced upregulation of functional somatostatin type 2 receptors in human
      pancreatic neuroendocrine tumor cells.
AB  - Somatostatin receptors are a pivotal target for treatment of pancreatic
      neuroendocrine tumors (pNET), either with somatostatin analogues (SSA) or
      radiolabeled SSA. The highest affinity target for the most commonly used SSA is
      the somatostatin receptor type 2 (sst2 ). An important factor that may complicate
      treatment efficacy, is the variable number of receptors expressed on pNETs. Gene
      expression is subject to complex regulation, in which epigenetics has a central
      role. In this study we explored the possible role of epigenetic modifications in
      the variations in sst2 expression levels in two human pNET cell lines, BON-1 and
      QGP-1. We found upregulation of sst2 mRNA after treatment with the epidrugs 5-aza
      2'-deoxycytidine (5-aza-dC) and valproic acid (VPA), an increased uptake of
      radiolabeled octreotide, as well as increased sensitivity to the SSA octreotide
      in functional cAMP inhibition. At epigenetic level we observed low methylation
      levels of the sst2 gene promoter region irrespective of expression. Activating
      histone mark H3K9Ac can be regulated with epidrug treatment, with an angle of
      effect corresponding to the effect on mRNA expression. Repressive histone mark
      H3K27me3 is not regulated by either 5-aza-dC or VPA. We conclude that epidrug
      treatment, in particular with combined 5-aza-dC and VPA treatment, might hold
      promise for improving and adding to current SSA treatment strategies of patients
      with pNETs.

PMID- 29599908
TI  - Regulatory B cells induced by pancreatic cancer cell-derived interleukin-18
      promote immune tolerance via the PD-1/PD-L1 pathway.
AB  - Dysregulation of regulatory B cells (Bregs), a type of immunosuppressive
      lymphocyte, are associated with development of autoimmune diseases and cancers.
      Bregs produce immune tolerance-inducing cell surface molecules and tolerogenic
      cytokines (interleukin [IL]-10 and transforming growth factor-beta). We
      previously showed that levels of the inflammatory cytokine IL-18 were increased
      in patients with pancreatic cancer. In the present study study, we found that
      pancreatic cancer cell-derived IL-18 increases Breg-induced immunosuppression. IL
      18 also promoted B-cell proliferation and IL-10 expression in vivo and in vitro.
      In addition, IL-18 upregulated membrane PD-1 in B cells and inhibited the
      antibody-dependent cellular cytotoxicity of Tc cells and natural killer cells.
      Finally, the combination of a natural IL-18 inhibitor (IL-18BP) and a PD-1/PD-L1
      inhibitor suppressed tumor growth and metastasis in a murine pancreatic cancer
      model. Our results show that IL-18 and PD-1/PD-L1 could be therapeutic targets in
      pancreatic cancer.

PMID- 29599909
TI  - RNA-binding protein AUF1 suppresses miR-122 biogenesis by down-regulating Dicer1
      in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the common cancers worldwide, especially
      in developing countries. Although the chronic infections of hepatitis B and C
      viruses have been established as the etiological factors of HCC, the mechanism
      for the tumorigenesis and development of HCC is still unclear. The liver-specific
      microRNA-122 (miR-122), an established tumor-suppressor miRNA, is often down
      regulated in HCC, while the underlying mechanism is not well understood. Here we
      report that the AU-rich element-binding factor AUF1 suppresses the expression of
      Dicer1, the type III RNase that is required for microRNA maturation, leading to
      the inhibited biogenesis of miR-122. Overexpression of AUF1 led to the decreased
      expression of Dicer1 and miR-122, while the level of the miR-122 precursor (pre
      miR-122) was increased. On the other hand, siRNA of AUF1 (siAUF1) increased the
      levels of Dicer1 mRNA and miR-122, but it reduced the abundance of pre-miR-122.
      Consistent with the reported data, this study demonstrated that AUF1 and Dicer1
      showed opposite expression pattern in both human HCC tissues and cell lines. In
      addition, AUF1 inhibited the expression of Dicer1 by interacting with the 3'
      untranslated region (3'UTR) and coding region of DICER1 mRNA. Moreover, the
      knockdown of AUF1 by siRNA altered the expression of other miRNAs and promoted
      HCC cell death. In conclusion, AUF1 down-regulates the expression miR-122 by
      interacting with the 3'UTR and coding region of DICER1 mRNA and suppressing
      Dicer1 expression. The AUF1/Dicer1/miR-122 pathway might play a critical role in
      the development of HCC.

PMID- 29599910
TI  - Developing a genetic signature to predict drug response in ovarian cancer.
AB  - There is a lack of personalized treatment options for women with recurrent
      platinum-resistant ovarian cancer. Outside of bevacizumab and a group of poly ADP
      ribose polymerase inhibitors, few options are available to women that relapse. We
      propose that efficacious drug combinations can be determined via molecular
      characterization of ovarian tumors along with pre-established pharmacogenomic
      profiles of repurposed compounds. To that end, we selectively performed multiple
      two-drug combination treatments in ovarian cancer cell lines that included
      reactive oxygen species inducers and HSP90 inhibitors. This allowed us to select
      cell lines that exhibit disparate phenotypes of proliferative inhibition to a
      specific drug combination of auranofin and AUY922. We profiled altered
      mechanistic responses from these agents in both reactive oxygen species and HSP90
      pathways, as well as investigated PRKCI and lncRNA expression in ovarian cancer
      cell line models. Generation of dual multi-gene panels implicated in resistance
      or sensitivity to this drug combination was produced using RNA sequencing data
      and the validity of the resistant signature was examined using high-density RT
      qPCR. Finally, data mining for the prevalence of these signatures in a large
      scale clinical study alluded to the prevalence of resistant genes in ovarian
      tumor biology. Our results demonstrate that high-throughput viability screens
      paired with reliable in silico data can promote the discovery of effective,
      personalized therapeutic options for a currently untreatable disease.

PMID- 29599911
TI  - Effects of carbon ion beam alone or in combination with cisplatin on malignant
      mesothelioma cells in vitro.
AB  - Malignant mesothelioma (MM) is extremely aggressive and a typical refractory
      cancer. In this study we investigated how effective on killing MM cells by carbon
      ion beam alone or in combination with cisplatin (CDDP) in vitro. Carbon ion beam
      (at the center of SOBP with 50 keV/um of average LET) dose-independently
      suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP
      (25 MUM) significantly enhanced its action. Relative biological effectiveness
      (RBE) values at 73 keV/MUm and 13 keV/MUm portion of carbon ion beam was
      estimated as 2.82-2.93 and 1.19-1.22 at D10 level relative to X-ray, respectively
      by using colony formation assay. Quantitative real time PCR analysis showed that
      expression of apoptosis-related BAX and autophagy-related Beclin1 and ATG7 was
      significantly enhanced by carbon ion beam alone or in combination with CDDP.
      Apoptosis analysis showed that caspase 3/7 activity and the percentage of
      apoptotic cells was dose-dependently increased after carbon ion beam and it was
      further increased when combined with CDDP. Spheroid formation ability of cancer
      stem like CD44+/CD26+ cells was significantly inhibited by carbon ion beam
      combined with CDDP. Besides, carbon ion beam combined with cisplatin
      significantly inhibited cell cycle progression (sub-G1 arrest) and induced more
      large number of gammaH2AX foci. In conclusion, carbon ion beam combined with CDDP
      has superior potential to kill MM cells including CSCs with enhanced apoptosis.

PMID- 29599912
TI  - Coagulation cascade and complement system in systemic lupus erythematosus.
AB  - This study was conducted to (1) characterize coagulation cascade and complement
      system in systemic lupus erythematosus (SLE); (2) evaluate the associations
      between coagulation cascade, complement system, inflammatory response and SLE
      disease severity; (3) test the diagnostic value of a combination of D-dimer and
      C4 for lupus activity. Transcriptomics, proteomics and metabolomics were
      performed in 24 SLE patients and 24 healthy controls. The levels of ten
      coagulations, seven complements and three cytokines were measured in 112 SLE
      patients. Clinical data were collected from 2025 SLE patients. The analysis of
      multi-omics data revealed the common links for the components of coagulation
      cascade and complement system. The results of ELISA showed coagulation cascade
      and complement system had an interaction effect on SLE disease severity, this
      effect was pronounced among patients with excess inflammation. The analysis of
      clinical data revealed a combination of D-dimer and C4 provided good diagnostic
      performance for lupus activity. This study suggested that coagulation cascade and
      complement system become 'partners in crime', contributing to SLE disease
      severity and identified the diagnostic value of D-dimer combined with C4for lupus
      activity.

PMID- 29599913
TI  - Time-dependent effects of late-onset dietary intake of salidroside on lifespan
      and age-related biomarkers of the annual fish Nothobranchius guentheri.
AB  - One of the most studied and widely accepted conjectures of aging process is the
      oxidative stress theory. Previous studies have shown that salidroside can protect
      D-galactose-induced mouse model against aging and a formulation of Rhodiola rosea
      extracts (SHR-5) containing salidroside increases lifespan of fruit fly. However,
      direct evidence linking salidroside itself with the observed anti-aging effect in
      vivo and relevant molecular mechanisms are poorly defined. In this study, we
      first demonstrated that salidroside exhibited a time-dependent effect, and late
      onset long-term salidroside dietary intake extended the lifespan in the annual
      fish Nothobranchius guentheri. We then showed that salidroside reduced the
      accumulation of lipofuscin in the gills as well as the levels of protein
      oxidation, lipid peroxidation and reactive oxygen species in the muscles;
      enhanced the activities of catalase, glutathione peroxidase, and superoxide
      dismutase in the fish; and decelerated the increase of P66shc, a critical factor
      for regulation of intracellular reactive oxygen species contents. Collectively,
      these data indicate that salidroside can prolong the lifespan and retard the
      onset of age-related biomarkers via the antioxidant system in aging fish. It also
      suggests that salidroside may have a potential usefulness in prolonging the
      lifespan of the elderly.

PMID- 29599914
TI  - Serum microRNAs as predictors of risk for non-muscle invasive bladder cancer.
AB  - MicroRNAs (miRNAs) are implicated in the development of nearly all cancers and
      may function as promising biomarkers for early detection, diagnosis and
      prognosis. We sought to investigate the role of serum miRNAs as potential
      diagnostic biomarkers or biomarkers of risk for early-stage bladder cancer.
      First, we profiled global serum miRNAs in a pilot set of 10 non-muscle invasive
      bladder cancer (NMIBC) cases and 10 healthy controls matched on age, gender and
      smoking status. Eighty nine stably detectable miRNAs were selected for further
      testing and quantification by high-throughput Taqman analysis using the Fluidigm
      BioMark HD System to assess their association with NMIBC risk in both discovery
      and validation sets totaling 280 cases and 278 controls. We found miR-409-3p and
      six miRNAs expression ratios were significantly associated with risk of bladder
      cancer in both discovery and validation sets. Interestingly, we identified
      expression of miR-409-3p and miR-342-3p inversely correlated with age and age of
      onset of NMIBC. A risk score was generated based on the combination of three
      miRNA ratios (miR-29a-3p/miR-222-3p, miR-150-5p/miR-331-3p, miR-409-3p/miR-423
      5p). In dichotomized analysis, we found individuals with high risk score showed
      increased risk of bladder cancer in the discovery, validation, and combined sets.
      Pathway enrichment analyses suggested altered miRNAs and cognate target genes are
      linked to the retinoid acid receptor (RAR) signaling pathway. Overall, these
      results suggested specific serum miRNA signatures may serve as noninvasive
      predictors of NMIBC risk. Biological insights underlying bladder cancer
      development based on the pathway enrichment analysis may reveal novel therapeutic
      targets for personalized medicine.

PMID- 29599915
TI  - Pertuzumab, trastuzumab and eribulin mesylate therapy for previously treated
      advanced HER2-positive breast cancer: a feasibility study with analysis of
      biomarkers.
AB  - The standard treatment for advanced human epidermal growth factor receptor 2
      (HER2)-positive breast cancer is the triple combination of pertuzumab,
      trastuzumab and docetaxel, but some patients cannot tolerate taxane. To explore a
      non-taxane triple therapy, we conducted a feasibility study of pertuzumab,
      trastuzumab and eribulin mesylate (PTE) therapy for previously treated advanced
      HER2-positive breast cancer with analyses of quality of life and biomarkers. Ten
      patients were enrolled, two of whom had a history of docetaxel allergy. The
      median number of prior regimens was 3. The most common Grade 3 toxicities were
      leukopenia (70%) and neutropenia (70%). Grade 4 or 5 adverse events were not
      observed. An improving trend for the Functional Assessment of Cancer Therapy
      Breast (FACT-B) score at 3 months was observed. Eight cases were included in the
      biomarker analysis. The peripheral CD8+ T cell/ CD4+Foxp3+ regulatory T cells
      (Tregs) ratio was significantly increased (p = 0.039). The frequency of
      peripheral Tregs was associated with the trastuzumab trough concentration (p =
      0.019). In a non-clinical analysis, Eribulin mesylate significantly inhibited
      Ser473 Akt phosphorylation in PIK3CA wild-type cells and mutated cells. These
      results suggest that PTE therapy is a feasible and promising option for advanced
      HER2-positive breast cancer. Further investigation is warranted.

PMID- 29599916
TI  - PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours.
AB  - Background: The extent of resistance to immune surveillance in patients with well
      differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs)
      is unknown. Methods: Patients diagnosed with Wd Si-NETs (excluding appendix,
      which are considered to have a different biology to other midgut NETs) were
      eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and
      tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in
      archival tissue by immunohistochemistry (IHC); reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results.
      Results: Of 109 patients screened, 62 were eligible: 54.8% were male; median age
      was 63.7 years (95%-CI 59.7-67.2); disease stage II: 4.8%, III: 40.3% and IV:
      54.8%; 41.9% were functional. Analysed samples (67.1% from primary tumours, 32.9%
      from metastases) were of grade 1 (67.1%) or 2 (32.86%) with a median Ki-67 of 2%.
      From the total of 62 eligible patients, 70 and 63 samples were suitable for IHC
      and RT-qPCR analysis, respectively. PD-L1 expression within tumour cells and TILs
      were identified in 12.8% and 24.3% of samples respectively; 30% of samples showed
      PD-L1 expression within tumour cells and/or TILs. PD-1 was present in TILs in
      22.8% of samples. Majority of samples showed significant presence of CD4+ (focal
      42.86%; moderate 2.86%) and CD8+ (focal 92.86%; moderate 4.29%) TILs. IHC
      findings were confirmed with RT-qPCR; which showed higher expression levels of PD
      L1 (p-value 0.007) and PD-1 (p-value 0.001) in samples positive for IHC compared
      to negative-IHC. Conclusions: Thirty-percent of patients express PD-L1 within
      tumour cells and/or TILs. Identification of presence of TILs was also significant
      and warrant the investigation of immunotherapy in this setting.

PMID- 29599917
TI  - PGE2 mediates EGFR internalization and nuclear translocation via caveolin
      endocytosis promoting its transcriptional activity and proliferation in human
      NSCLC cells.
AB  - Prostaglandin E2 (PGE2) contributes to tumor progression by promoting cancer cell
      growth, invasion and by creating a favorable pro-tumor microenvironment. PGE2 has
      been reported to transactivate and internalize into the nucleus receptor tyrosine
      kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor
      progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC)
      cells, PGE2 induces EGFR nuclear translocation via different dynamin-dependent
      endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects
      nuclear EGFR target gene expression and mediates tumor cell proliferation.
      Indeed, we find that PGE2 induces EGFR internalization and consequent nuclear
      import through Clathrin- and Caveolin-mediated endocytosis and through the
      interaction of EGFR with Importin beta1. Within the nucleus, EGFR forms a complex
      with STAT3, an event blocked by ablation of Clathrin Heavy Chain or Caveolin-1.
      The combination of EGF and PGE2 prolongs nuclear EGFR transcriptional activity
      manifested by the upregulation of CCND1, PTGS2, MYC and NOS2 mRNA levels and
      potentiates nuclear EGFR-induced NSCLC cell proliferation. Additionally, NSCLC
      patients with high expression of a nuclear EGFR gene signature display shorter
      survival times than those with low expression, thus showing a putative
      correlation between nuclear EGFR and poor prognosis in NSCLC. Together, our
      findings indicate a complex mechanism underlying PGE2-induced EGF/EGFR signaling
      and transcriptional control, which plays a key role in cancer progression.

PMID- 29599918
TI  - FC-99 ameliorates sepsis-induced liver dysfunction by modulating
      monocyte/macrophage differentiation via Let-7a related monocytes apoptosis.
AB  - Background: The liver is a vital target for sepsis-related injury, leading to
      inflammatory pathogenesis, multiple organ dysfunction and high mortality rates.
      Monocyte-derived macrophage transformations are key events in hepatic
      inflammation. N1-[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine (FC-99)
      previously displayed therapeutic potential on experimental sepsis. However, the
      underlying mechanism of this protective effect is still not clear. Results: FC-99
      treatment attenuated the liver dysfunction in septic mice that was accompanied
      with reduced numbers of pro-inflammatory Ly6Chi monocytes in the peripheral blood
      and CD11b+F4/80lo monocyte-derived macrophages in the liver. These effects were
      attributed to the FC-99-induced apoptosis of CD11b+ cells. In PMA-differentiated
      THP-1 cells, FC-99 repressed the expression of CD11b, CD14 and caspase3 and
      resulted in a high proportion of Annexin V+ cells. Moreover, let-7a-5p expression
      was abrogated upon CLP stimulation in vivo, whereas it was restored by FC-99
      treatment. TargetScan analysis and luciferase assays indicated that the anti
      apoptotic protein BCL-XL was targeted by let-7a-5p. BCL-XL was inhibited by FC-99
      in order to induce monocyte apoptosis, leading to the impaired monocyte-to
      macrophage differentiation. Materials and Methods: Murine acute liver failure was
      generated by caecal ligation puncture surgery after FC-99 administration; Blood
      samples and liver tissues were collected to determine the monocyte/macrophage
      subsets and the induction of apoptosis. Human acute monocytic leukemia cell line
      (THP-1) cells were pretreated with FC-99 followed by phorbol-12-myristate-13
      acetate (PMA) stimulation, in order to induce monocyte-to-macrophage
      differentiation. The target of FC-99 and the mechanistic analyses were conducted
      by microarrays, qRT-PCR validation, TargetScan algorithms and a luciferase report
      assay. Conclusions: FC-99 exhibits potential therapeutic effects on CLP-induced
      liver dysfunction by restoring let-7a-5p levels.

PMID- 29599919
TI  - Trib2 expression in granulocyte-monocyte progenitors drives a highly drug
      resistant acute myeloid leukaemia linked to elevated Bcl2.
AB  - Trib2 pseudokinase has oncogenic and tumour suppressive functions depending on
      the cellular context. We investigated the ability of Trib2 to transform different
      haemopoietic stem and progenitor cells (HSPCs). Our study identified the
      granulocyte-macrophage progenitor (GMP) subpopulation as a potent leukaemia
      initiating cell of Trib2-driven AML in vivo. Trib2 transformed GMPs generated a
      fully penetrant and short latency AML. AML cells expressing elevated Trib2 led to
      a chemoresistant phenotype following chemotherapy treatment. We show that Trib2
      overexpression results in an increase in BCL2 expression, and high Trib2
      expressing cells are highly sensitive to cell killing by BCL2 inhibition
      (ABT199). Combined treatment with chemotherapeutic agents and BCL2 inhibition
      resulted in synergistic killing of Trib2+ AML cells. Trib2 transformed GMP AML
      cells showed more chemoresistance compared with HSPC derived Trib2 AML cells
      associated with higher Bcl2 expression. There is significant correlation of high
      TRIB2 and BCL2 expression in patient derived human AML cells. These data
      demonstrate that the cell of origin influences the leukaemic profile and
      chemotherapeutic response of Trib2+ AML. Combined TRIB2 and BCL2 expression in
      AML cells may have clinical utility relevant for monitoring drug resistance and
      disease relapse.

PMID- 29599920
TI  - Molecular dissection of engraftment in a xenograft model of myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) are oligoclonal disorders of the hematopoietic
      stem cells (HSC). Recurrent gene mutations are involved in the MDS
      physiopathology along with the medullar microenvironment. To better study the
      heterogeneity of MDS, it is necessary to create patient derived xenograft (PDX).
      We have reproduced a PDX model by xenografting HSC (CD34+) and mesenchymal
      stromal cells (MSC) in NOD/SCID/IL2rgamma-/- mice with primary samples from one
      RAEB2, two RAEB1 and one RARS patients harboring karyotype abnormalities and gene
      mutations. The average human chimerisms ranged from 59.7% to 0.0175% for the 4
      patients. Secondary grafts (G2) were only performed for mice derived from the
      RAEB2 patient and the average human chimerism was 53.33%. G1 mice 1 and 2, and
      their derived G2 mice showed less than 20% of medullar blasts whereas mouse 3 and
      the resulting G2 mice transformed to AML. Clonal architecture was dissected in
      the different hematopoietic progenitors (HP) harvested from G1 and G2 mice. By
      direct Sanger sequencing, we found the 4 initial mutations in each HP
      subpopulation and those mutations had the same variant allele frequency in the
      CD34+ CD38- HSC from G1 and G2 mice by next generation sequencing (NGS). Targeted
      NGS analysis done in HSC of mouse 3 did not show any additional driver gene
      mutations explaining the transformation to AML. To conclude, we have generated a
      PDX mouse model that perfectly reproduces the MDS founder clone which is stable
      over time, allowing us to consider this system as a powerful tool to test
      therapeutic approaches.

PMID- 29599921
TI  - A multicenter round robin test of PD-L1 expression assessment in urothelial
      bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis
      prediction after radical cystectomy.
AB  - Background: Immunohistochemical PD-L1 assessment is currently used to identify
      responders towards checkpoint inhibitors although it is limited by inter-observer
      effects. Here, we conducted a multi-center round robin test to prove the
      possibility of assessing the PD-L1 status by gene expression to avoid inter
      observer effects. Patients and methods: Gene expression of PD-L1 was analyzed in
      a total of 294 samples (14 cases non-muscle invasive and muscle-invasive bladder
      cancer; MIBC) in seven centers by a RT-qPCR kit and compared with
      immunohistochemical scoring of three pathologists (DAKO, 22c3). Both assays were
      compared towards prognosis prediction in a cohort of 88 patients with MIBC.
      Results: PD-L1 gene expression revealed very high inter center correlation
      (centrally extracted RNA: r = 0.68-0.98, p <= 0.0076; locally extracted RNA: r =
      0.81-0.98, p <= 0.0014). IHC Inter-observer concordance was moderate to
      substantial for immune cells (IC), fair for combined IC/ tumor cell (TC) (IC:
      kappa = 0.50-0.61; IC + TC: kappa = 0.50), and fair for TC scoring (kappa = 0.26
      0.35). Gene expression assessment resulted in more positive cases (9/14 cases
      positive vs. 6/14 cases [IHC]) which could be validated in the independent
      cohort. Positive mRNA status was associated with significantly better overall and
      disease-specific survival (5-year OS: 50% vs. 26%, p = 0.0042, HR = 0.48; 5 year
      DSS: 65% vs. 40%, p = 0.012, HR = 0.49). The 1% IHC IC cut-off also revealed
      significant better OS (5 year OS: 58% vs. 31%, p = 0.036, HR = 0.62). Conclusion:
      Gene expression showed very high inter-center agreement. Gene expression
      assessment also resulted in more positive cases and revealed better prognosis
      prediction. PD-L1 mRNA expression seems to be a reproducible and robust tool for
      PD-L1 assessment.

PMID- 29599922
TI  - Modularity of the metabolic gene network as a prognostic biomarker for
      hepatocellular carcinoma.
AB  - Abnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both
      aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production
      and biomass synthesis. Understanding the metabolic reprogramming in cancer can
      help design therapies to target metabolism and thereby to improve prognosis. We
      have previously argued that more malignant tumors are usually characterized by a
      more modular expression pattern of cancer-associated genes. In this work, we
      analyzed the expression patterns of metabolism genes in terms of modularity for
      371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA).
      We found that higher modularity significantly correlated with glycolytic
      phenotype, later tumor stages, higher metastatic potential, and cancer
      recurrence, all of which contributed to poorer prognosis. Among patients with
      recurred tumors, we found the correlation of higher modularity with worse
      prognosis during early to mid-progression. Furthermore, we developed metrics to
      calculate individual modularity, which was shown to be predictive of cancer
      recurrence and patients' survival and therefore may serve as a prognostic
      biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged
      by decreased host survival probability, had more modular expression patterns of
      metabolic genes. These results may be used to identify cancer driver genes and
      for drug design.

PMID- 29599923
TI  - Umbilical cord blood mononuclear cell therapy induces clinical remission of
      steroid-dependent or -resistant ulcerative colitis patients.
AB  - To compare the efficacy and safety of umbilical cord blood mononuclear cells
      (CBMNC) and azathioprine (AZA) in the treatment of patients with steroid
      dependent or -resistant ulcerative colitis. One hundred and six patients
      diagnosed with steroid-dependent or -resistant ulcerative colitis were studied
      retrospectively, including 36 patients treated with CBMNC and 70 treated with
      AZA. To reduce confounding bias due to retrospective nature of this study, the
      propensity score matching system was applied to equipoise the pretreatment data
      of two groups. After matching, 35 matched pairs (1:1) were created. The ratios of
      clinical remission, clinical response and endoscopic mucosal healing, Mayo score,
      and major complications were compared between two groups at weeks 8, 16, and 36
      after treatment. The results demonstrated that the ratios of clinical remission
      (80% vs. 57%, P < 0.05) and mucosal healing (74% vs. 51%, P < 0.05) were
      significantly higher in CBMNC-treated patients compared with those in AZA-treated
      patients at week 8. The erythrocyte sedimentation rate was significantly
      decreased in CBMNC group compared with that in AZA-treated group (14.5 +/- 3.9
      mm/h vs. 18.0 +/- 5.7 mm/h, P < 0.01) at week 8. In AZA group, 2 patients had
      neutropenia and 3 patients had elevated alanine aminotransferase levels, whereas
      no obvious side-effects were observed in CBMNC-treated group. Our results reveal
      that CBMNC therapy appears to be an effective and safe strategy for patients with
      steroid-dependent or -resistant ulcerative colitis. Further prospective studies
      are needed to define the potential roles and mechanisms of CBMNC in the treatment
      of refractory ulcerative colitis.

PMID- 29599924
TI  - Asiatic acid attenuates lipopolysaccharide-induced injury by suppressing
      activation of the Notch signaling pathway.
AB  - Sepsis is a severe multisystem disease with high mortality rates and limited
      treatment options. However, advances during the last decade have opened
      opportunities to develop novel therapeutic strategies. The Notch signaling
      pathway plays a critical role in inflammation, and its inhibition offers an
      avenue to treat inflammatory diseases, such as sepsis. Asiatic acid (AA), a
      triterpenoid isolated from Centella asiatica, reportedly exerts anti-oxidant,
      anti-tumor, and anti-inflammatory effects, but its mechanisms remain unclear. In
      our study, we found that AA decreased levels of interleukin-1beta (IL-1beta), IL
      6, alanine aminotransferase and blood urea nitrogen in serum; attenuated liver,
      lung and kidney damage; and improved the survival among mice with experimental
      sepsis. AA also reduced lipopolysaccharide-stimulated expression of
      proinflammatory mediators, including nitric oxide, IL-1beta and IL-6 in RAW 264.7
      macrophages. Notably, we demonstrated for the first time that AA is a novel small
      molecule inhibitor of the Notch signaling pathway. Its effects include
      upregulation of Notch receptor (Notch3) and delta-like ligand (DLL4), inhibition
      of Notch3 binding to the IL-6 promoter and regulation of mitochondrial function.
      These novel effects of AA may provide new approaches and strategies for the
      treatment of inflammatory disorders.

PMID- 29599925
TI  - A porcine placental extract prevents steatohepatitis by suppressing activation of
      macrophages and stellate cells in mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in
      the liver. NAFLD is associated with hepatic inflammation and oxidative stress,
      resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis.
      Placental extracts have been used to treat various chronic diseases due to their
      antioxidative effect. However, the effects of the extracts on the development of
      NASH have yet to be elucidated. Here, we demonstrated that supplementation with
      an oral porcine placental extract (PPE) attenuated lipid accumulation and
      peroxidation, insulin resistance, inflammatory and stress signaling, and
      fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat
      diet. The PPE reduced the number of M1-like liver macrophages, but increased the
      number of anti-inflammatory M2-like macrophages, resulting in a predominance of
      M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE
      suppressed lipopolysaccharide-induced M1 polarization in isolated murine
      peritoneal macrophages, whereas it facilitated interleukin 4-induced M2
      polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC)
      activation associated with the attenuated transforming growth factor-beta/Smad3
      signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE
      may be a potential approach to prevent NASH by limiting lipid peroxidation,
      promoting M2 macrophage polarization, and attenuating HSC activation.

PMID- 29599926
TI  - Role of cooperative groups and funding source in clinical trials supporting
      guidelines for systemic therapy of breast cancer.
AB  - Introduction: Clinical research is conducted by academia, cooperative groups
      (CGs) or pharmaceutical industry. Here, we evaluate the role of CGs and funding
      sources in the development of guidelines for breast cancer therapies. Results: We
      identified 94 studies. CGs were involved in 28 (30%) studies while industry
      either partially or fully sponsored 64 (68%) studies. The number of industry
      funded studies increased over time (from 0% in 1976 to 100% in 2014; p for trend
      = 0.048). Only 10 (11%) government or academic studies were identified. Studies
      conducted by GCs included a greater number of subjects (median 448 vs. 284; p =
      0.015), were more common in the neo/adjuvant setting (p < 0.0001), and were more
      often randomized (p = 0.018) phase III (p < 0.0001) trials. Phase III trial
      remained significant predictor for CG-sponsored trials (OR 7.1 p = 0.004) in a
      multivariable analysis. Industry funding was associated with higher likelihood of
      positive outcomes favoring the sponsored experimental arm (p = 0.013) but this
      relationship was not seen for CG-sponsored trials (p = 0.53). Materials and
      Methods: ASCO, ESMO, and NCCN guidelines were searched to identify systemic anti
      cancer therapies for early-stage and metastatic breast cancer. Trial
      characteristics and outcomes were collected. We identified sponsors and/or the
      funding source(s) and determined whether CGs, industry, or government or academic
      institutions were involved. Chi-square tests were used for comparison between
      studies. Conclusions: Industry funding is present in the majority of studies
      providing the basis for which recommendations about treatment of breast cancer
      are made. Industry funding, but not CG-based funding, was associated with higher
      likelihood of positive outcomes in clinical studies supporting guidelines for
      systemic therapy.

PMID- 29599927
TI  - The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta
      analysis.
AB  - Background & Aims: Quite a few studies had investigated the correlation between
      CXC chemokine receptor 2 (CXCR2) and cancer. This meta-analysis was aimed to
      comprehensively summarize the previous studies and to explore the prognostic
      value of CXCR2 in patients with cancer. Materials and Methods: An adequate
      literature search in EMBASE and PubMed was conducted. Articles in English which
      have reported CXCR2 expression in patients and enough data to calculate hazard
      ratio (HR) were included. Effect estimates were analyzed with Review Manager 5.2.
      The endpoint was overall survival (OS) and recurrence-free survival (RFS).
      Result: Twelve studies from 10 publications with a total of 2,461 patients were
      identified. It was shown that high level of CXCR2 was significantly associated
      with poorer overall survival (OS) (HR = 1.69, 95% CI = 1.46-1.96, p < 0.0001, I2
      = 45%) and RFS (HR = 1.50, 95% CI = 1.25-1.80, p < 0.0001, I2 = 6%). The analyses
      of different analysis models (univariate or multivariate models), sample size (<
      300 or >= 300) and ethnicity (Asian and Caucasian) have indicated the negative
      impact of CXCR2 over-expression on survival of patients with cancer. Stratified
      by cancer type, high-expression of CXCR2 was associated with unfavorable OS in
      laryngeal squamous cell carcinoma, lung cancer, pancreatic ductal carcinoma,
      clear-cell renal cell carcinoma and hepatocellular carcinoma; however, there was
      significant difference between high- and low-expression of CXCR2 in digestive
      tract cancer (esophageal adenocarcinoma and squamous cell carcinoma procession,
      resected esophageal carcinoma, esophageal cancer and gastric cancer).
      Conclusions: CXCR2 is an unfavorable predictor in terms of OS and RFS in patients
      with cancer except for digestive tract cancer and is related with poorer
      prognostic.

PMID- 29599928
TI  - The association of 5HT2A and 5HTTLPR polymorphisms with Alzheimer's disease
      susceptibility: a meta-analysis with 6945 subjects.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease.
      Relationships of 5HT2A and 5HTTLPR polymorphisms and AD risk have been widely
      investigated previously, whereas results derived from these studies were
      inconclusive and controversial. The aim of this study was to investigate the
      association of the 5-HT2A and 5HTTLPR polymorphisms and AD using a meta-analysis
      of existing literatures. Studies were collected using PubMed, Web of Science, the
      Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI) and
      Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      assess associations. As a result, a total of 7 publications for 5-HT2A T102C and
      16 publications for 5HTTLPR (L/S) comprised 3255 cases and 3690 controls
      fulfilled the inclusion criteria. Significant association was covered between
      allelic and recessive models of 5-HT2A T102C and AD (allelic model: p = 0.003, OR
      [95% CI] = 1.23 [1.07, 1.40]; recessive model: p = 0.03, OR [95% CI] = 1.28
      [1.02, 1.59]). Subsequently, we conducted subgroup analysis for 5-HT2A T102C
      polymorphism based on ethnicities and APOE epsilon4, and identified a
      significantly increased risk for the allelic and dominant models of 5-HT2A T102C
      and AD in Asian subgroup (allelic model: p = 0.002, OR [95% CI] = 1.42 [1.14,
      1.78]; dominant model: p = 0.02, OR [95% CI] = 1.60 [1.09, 2.35]) and subgroup
      without APOE epsilon4 (allelic model: p = 0.02, OR [95% CI] = 1.44 [1.05, 1.99];
      dominant model: p = 0.0008, OR [95% CI] = 2.49 [1.46, 4.25]). Nevertheless, the
      pooled analyses suggested no significant association between allelic, dominant,
      and recessive models of 5HTTLPR (L/S) and AD (p > 0.05). In conclusion, our meta
      analysis demonstrates that 5HT2A C10T, but not 5HTTLPR (L/S), might increase risk
      for AD.

PMID- 29599929
TI  - Tooth loss and cancer risk: a dose-response meta analysis of prospective cohort
      studies.
AB  - Conflicting results to identify the relationship between tooth loss and cancer
      risk. Therefore, a dose-response meta-analysis was performed to clarify and
      quantitative assessed the correlation between tooth loss and cancer risk. Up to
      March 2017, 25 observational epidemiological studies were included in current
      meta-analysis. Tooth loss was significantly associated with a higher risk of
      cancer. Additionally, tooth loss was associated with significantly a higher risk
      of esophageal cancer, gastric cancer, head and neck cancer, colorectal cancer,
      pancreas cancer, lung cancer, prostate cancer, bladder cancer and hematopoietic
      cancer. Subgroup analysis showed consistent findings. Furthermore, a significant
      dose-response relationship was observed between tooth loss and cancer risk.
      Increasing per 10 of tooth loss was associated with a 9% increment of cancer
      risk, 14% increment of esophageal cancer risk, 9% increment of gastric cancer
      risk, 31% increment of head and neck cancer risk, 4% increment of colorectal
      cancer risk, 7% increment of pancreas cancer risk, 19% increment of lung cancer
      risk, 2% increment of bladder cancer risk and 3% increment of hematopoietic
      cancer risk. Considering these promising results, tooth loss might be harmful for
      health. Large sample size, different ethnic population and different cancer type
      are warranted to validate this association.

PMID- 29599930
TI  - Does antipsychotic drug use increase the risk of long term mortality? A
      systematic review and meta-analysis of observational studies.
AB  - Antipsychotics (AP) are widely used to treat schizophrenia and other psychiatric
      disorders. However, the association between the AP use and mortality risk is
      controversial. We searched PubMed, EMBASE, MEDLINE, PsycINFO, CINAHL, the
      Cochrane Library and four Chinese databases from inception to June 2016. All
      observational cohort or case-control studies reporting data on mortality outcomes
      in individuals exposed to AP drugs were included. This systematic review included
      68 studies involving 4,812,370 participants. Sixty-seven studies reported
      confounding factors, the most common being age, sex, race, concomitant
      medications, and comorbidities. For all-cause mortality, current users of AP and
      conventional antipsychotics (CAP) had higher mortality risk than did non-AP users
      [AP users: RR, 1.50; 95% CI, 1.12 to 1.99; CAP users: RR, 1.53; 95% CI, 1.16 to
      2.04]. However, the association between the current use of atypical
      antipsychotics (AAP) and the mortality was of borderline significance, and there
      was no significant difference for past users of AP. Mortality was higher in
      current CAP users than in current AAP users. For cardiac death and sudden death,
      current AP and CAP users also had higher mortality risk than non-AP users. A
      subgroup analysis showed a possible increased risk in patients with Parkinson's,
      but not in those with dementia, Alzheimer's disease, schizophrenia, delirium or
      stroke. An increased risk of all-cause mortality for patients ?65 years may also
      exist. AP exposure is associated with an approximately 1.5-fold increased
      mortality risk. This increased risk may be particularly prominent in patients
      with Parkinson's and those over 65 years old. Further studies are required to
      evaluate the mortality risk for individual AP drugs and diseases.

PMID- 29599931
TI  - Association between the Glutathione-S-transferase T1 null genotype and esophageal
      cancer susceptibility: a meta-analysis involving 11,163 subjects.
AB  - Background: Glutathione-S-Transferase T1 (GSTT1) null genotype has been shown to
      be associated with the risk of esophageal cancer. However, the results remain
      inconsistent. Thus a comprehensive meta-analysis was conducted to assess the
      strength of association between GSTT1 null genotype and the risk of esophageal
      cancer. Materials and Methods: A literature search of PubMed, Embase, China
      National Knowledge Infrastructure (CNKI) and Wanfang databases up to March 31,
      2017 was conducted and 30 eligible articles with 4482 cases and 6681 controls
      were finally recruited. The strength of correlation between GSTT1 polymorphism
      and the susceptibility of esophageal cancer was assessed by the crude odds ratios
      (ORs) with 95% confidence intervals (CIs). Subgroup analyses and sensitivity
      analyses were performed to further identify the association. Results: GSTT1 null
      genotype significantly increased the risk of esophageal cancer (OR = 1.20; 95% CI
      1.04-1.40; P < 0.05). In a subgroup analysis by ethnicity, GSTT1 null genotype
      was correlated with a significantly increased risk of esophageal cancer among
      Asians (OR = 1.33; 95% CI 1.12-1.58; P < 0.05), instead of Caucasians or Africans
      (OR = 0.91; 95% CI 0.65-1.26; P > 0.05 for Caucasians and OR = 1.32; 95% CI 0.98
      1.77; P > 0.05 for Africans). In the analysis by histological type, GSTT1 null
      genotype was correlated with a significantly increased risk of esophageal
      squamous cell carcinoma (OR = 1.34; 95% CI 1.12-1.61; P < 0.05), particularly
      among Asians (OR = 1.54; 95% CI 1.30-1.82; P < 0.05), but not among Caucasians or
      Africans (OR = 0.87; 95% CI 0.48-1.57; P > 0.05 for Caucasians and OR = 1.32; 95%
      CI 0.98-1.77; P > 0.05 for Africans). In addition, there is no significant
      correlation between GSTT1 null genotype and the risk of esophageal adenocarcinoma
      (OR = 0.98; 95% CI 0.71-1.35; P > 0.05). Conclusions: Our findings demonstrate
      that GSTT1 null genotype significantly increases esophageal cancer risk,
      particularly in Asians.

PMID- 29599932
TI  - Radial EBUS versus CT-guided needle biopsy for evaluation of solitary pulmonary
      nodules.
AB  - Objective: This study is aimed to compare the diagnostic yield, complications and
      influencing factors between Radial endobroncheal ultrasonography guided
      bronchoscopy(R-EBUS) and CT-guided needle biopsy (CT-PNB), for evaluation of
      solitary pulmonary nodules(SPNs). Matrials and Methods: 160 cases of consecutive
      patients with SPNs were enrolled and divided into R-EBUS and CT-PNB groups
      randomly. The diagnostic yield, complications and influencing factors between the
      two groups were evaluated. Results: Sensitivity of R-EBUS for malignancy was
      73.7% (42/57) and for benign, was 43.5% (10/23), overall diagnostic accuracy was
      65% (52/80). In CT-PNB group, overall diagnostic accuracy was 85% (68/80),
      sensitivity for malignancy was 87.9% (51/58), and for benign was 81.0% (17/21),
      respectively. Both overall diagnostic yield and incidence of complications in CT
      PNB group were higher than those in R-EBUS group (P = 0.006, P = 0.002). In R
      EBUS group, the factors affecting diagnostic yield were size (P = 0.027), the
      distance between SPNs and pleura (P = 0.031) and the location of the probe to
      lesions (P = 0.009). In CT-PNB group, the distance from the lesions to pleura was
      correlated with the incidence of pneumothorax (P = 0.001) and pulmonary
      haemorrhage (P = 0.042). The location of SPNs were adjacent to great vessels was
      another influencing factor for pulmonary haemorrhage (P = 0.042). Conclusions:
      Both R-EBUS and CT-PNB are valuable tools for diagnosis. SPNs located in medial
      1/2 of lung field, or were adjacent to great vessels may be fit for R-EBUS. Those
      SPNs located in lateral 1/2 of lung field, near to pleura or with less vessels
      around may be more suitable for CT-PNB.

PMID- 29599933
TI  - The genes associated with early-onset Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
      accounts for the most cases of dementia, which is characterized by the deposition
      of dense plaques of amyloid beta (Abeta) plaques and neurofibrillary tangles
      consisting of hyperphosphorylated tau. The two main types of AD can be classified
      as early-onset AD (EOAD, onset < 65 years) and late-onset AD (LOAD, onset >= 65
      years). Evidence from family and twin studies indicate that genetic factors are
      estimated to play a role in at least 80% of AD cases. The first milestone with
      linkage analysis revealed the mutations in APP, PSEN1, and PSEN2 genes that cause
      EOAD. But pathogenic mutations in these three genes can only explain a small
      fraction of EOAD families. The additional disease-causing genes have not yet been
      identified. This review provides an overview of the genetic basis of EOAD and the
      relationship between the functions of these risk genes and the neuropathologic
      features of AD. A better understanding of genetic mechanisms underlying EOAD
      pathogenesis and the potentially molecular mechanisms of neurodegeneration will
      lead to the development of effective diagnosis and treatment strategies for this
      devastating disease.

PMID- 29599935
TI  - BK virus-associated collecting duct carcinoma of the renal allograft in a kidney
      pancreas allograft recipient.
AB  - BK polyomavirus (BKV) nephropathy is a major concern in renal transplantation.
      Its main consequence is graft loss, which occurs in more than 50% of the cases.
      De novo renal cell carcinoma in renal allograft is a very rare event. Most of
      these tumors are papillary or clear cell carcinomas. We report herein the first
      case of collecting duct carcinoma of the renal allograft in a kidney-pancreas
      allograft adult recipient. Collecting duct carcinoma occurs long after the cure
      of a BKV nephropathy. At this time, BKV viremia and viruria were negative as well
      as the immunostaining for SV40 in the non-tumor kidney. The viral oncoprotein Tag
      persists only in the tumor cells. To preserve pancreas graft function, we
      maintained immunosuppression levels. After a 9-months follow-up, the evolution
      was free from clinical and radiological progression. The oncogenic role of BKV
      remains controversial in human cancers. However, strong experimental data have
      shown an association between BKV infection and urologic neoplasms. Further works
      might precise the exact role of polyomaviruses in renal carcinogenesis. In the
      meantime, clinical vigilance for early diagnostic of these tumors is mandatory
      after BKV nephropathy.

PMID- 29599934
TI  - Liquid biopsy provides new insights into gastric cancer.
AB  - Liquid biopsies have great promise for precision medicine as they provide
      information about primary and metastatic tumors via a minimally invasive method.
      In gastric cancer patients, a large number of blood-based biomarkers have been
      reported for their potential role in clinical practice for screening, early
      diagnosis, prognostic evaluation, recurrence monitoring and therapeutic
      efficiency follow-up. This current review focuses on blood liquid biopsies' role
      and their clinical implications in gastric cancer patients, with an emphasis on
      circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating non
      coding RNAs (ncRNAs). We also provide a brief discussion of the potential and
      limitations of liquid biopsies use and their future use in the routine clinical
      care of gastric cancer.

PMID- 29599936
TI  - Effect of varying computed tomography acquisition and reconstruction parameters
      on semi-automated clot volume quantification.
AB  - AIM: To examine effects of computed tomography (CT) image
      acquisition/reconstruction parameters on clot volume quantification in vitro for
      research method validation purposes. METHODS: This study was performed in
      conformance with HIPAA and IRB Regulations (March 2015-November 2016). A ten
      blood clot phantom was designed and scanned on a dual-energy CT scanner (SOMATOM
      Force, Siemens Healthcare GmBH, Erlangen, Germany) with varying pitch, iterative
      reconstruction, energy level and slice thickness. A range of clot and tube sizes
      were used in an attempt to replicate in vivo emboli found within central and
      segmental branches of the pulmonary arteries in patients with pulmonary emboli.
      Clot volume was the measured parameter and was analyzed by a single image analyst
      using a semi-automated region growing algorithm implemented in the FDA-approved
      Siemens syngo.via image analysis platform. Mixed model analysis was performed on
      the data. RESULTS: On the acquisition side, the continuous factor of energy
      showed no statistically significant effect on absolute clot volume quantification
      (P = 0.9898). On the other hand, when considering the fixed factor of pitch,
      there were statistically significant differences in clot volume quantification (P
      < 0.0001). On the reconstruction side, with the continuous factor of
      reconstruction slice thickness no statistically significant effect on absolute
      clot volume quantification was demonstrated (P = 0.4500). Also on the
      reconstruction side, with the fixed factor of using iterative reconstructions
      there was also no statistically significant effect on absolute clot volume
      quantification (P = 0.3011). In addition, there was excellent R2 correlation
      between the scale-measured mass of the clots both with respect to the CT measured
      volumes and with respect to volumes measure by the water displacement method.
      CONCLUSION: Aside from varying pitch, changing CT acquisition parameters and
      using iterative reconstructions had no significant impact on clot volume
      quantification with a semi-automated region growing algorithm.

PMID- 29599937
TI  - A Novel Interpretation for Arterial Pulse Pressure Amplification in Health and
      Disease.
AB  - Arterial pressure waves have been described in one dimension using several
      approaches, such as lumped (Windkessel) or distributed (using Navier-Stokes
      equations) models. An alternative approach consists of modeling blood pressure
      waves using a Korteweg-de Vries (KdV) equation and representing pressure waves as
      combinations of solitons. This model captures many key features of wave
      propagation in the systemic network and, in particular, pulse pressure
      amplification (PPA), which is a mechanical biomarker of cardiovascular risk. The
      main objective of this work is to compare the propagation dynamics described by a
      KdV equation in a human-like arterial tree using acquired pressure waves.
      Furthermore, we analyzed the ability of our model to reproduce induced elastic
      changes in PPA due to different pathological conditions. To this end, numerical
      simulations were performed using acquired central pressure signals from different
      subject groups (young, adults, and hypertensive) as input and then comparing the
      output of the model with measured radial artery pressure waveforms. Pathological
      conditions were modeled as changes in arterial elasticity (E). Numerical results
      showed that the model was able to propagate acquired pressure waveforms and to
      reproduce PPA variations as a consequence of elastic changes. Calculated
      elasticity for each group was in accordance with the existing literature.

PMID- 29599938
TI  - Accurate Rapid Lifetime Determination on Time-Gated FLIM Microscopy with Optical
      Sectioning.
AB  - Time-gated fluorescence lifetime imaging microscopy (FLIM) is a powerful
      technique to assess the biochemistry of cells and tissues. When applied to living
      thick samples, it is hampered by the lack of optical sectioning and the need of
      acquiring many images for an accurate measurement of fluorescence lifetimes.
      Here, we report on the use of processing techniques to overcome these
      limitations, minimizing the acquisition time, while providing optical sectioning.
      We evaluated the application of the HiLo and the rapid lifetime determination
      (RLD) techniques for accurate measurement of fluorescence lifetimes with optical
      sectioning. HiLo provides optical sectioning by combining the high-frequency
      content from a standard image, obtained with uniform illumination, with the low
      frequency content of a second image, acquired using structured illumination. Our
      results show that HiLo produces optical sectioning on thick samples without
      degrading the accuracy of the measured lifetimes. We also show that instrument
      response function (IRF) deconvolution can be applied with the RLD technique on
      HiLo images, improving greatly the accuracy of the measured lifetimes. These
      results open the possibility of using the RLD technique with pulsed diode laser
      sources to determine accurately fluorescence lifetimes in the subnanosecond range
      on thick multilayer samples, providing that offline processing is allowed.

PMID- 29599939
TI  - The Influence of Accreditation on the Sustainability of Organizations with the
      Brazilian Accreditation Methodology.
AB  - This research evaluates the influence of the Brazilian accreditation methodology
      on the sustainability of the organizations. Critical factors for implementing
      accreditation were also examined, including measuring the relationships
      established between these factors in the organization sustainability. The present
      study was developed based on the survey methodology applied in the organizations
      accredited by ONA (National Accreditation Organization); 288 responses were
      received from the top level managers. The analysis of quantitative data of the
      measurement models was made with factorial analysis from principal components.
      The final model was evaluated from the confirmatory factorial analysis and
      structural equation modeling techniques. The results from the research are vital
      for the definition of factors that interfere in the accreditation processes,
      providing a better understanding for accredited organizations and for Brazilian
      accreditation.

PMID- 29599940
TI  - A New Intelligent Medical Decision Support System Based on Enhanced Hierarchical
      Clustering and Random Decision Forest for the Classification of Alcoholic Liver
      Damage, Primary Hepatoma, Liver Cirrhosis, and Cholelithiasis.
AB  - Diagnosis of liver disease principally depends on physician's subjective
      knowledge. Automatic prediction of the disease is a critical real-world medical
      problem. This work presents an EHC-ERF-based intelligence-integrated model
      purposive to predict different types of liver disease including alcoholic liver
      damage, primary hepatoma, liver cirrhosis, and cholelithiasis. These diseases
      cause many clinical complications, and their accurate assessment is the only way
      for providing efficient treatment facilities to patients. EHC is deployed to
      divide the data into a hierarchy structure that is more informative for the
      disease predictions carried out by ERF. The occurrence of ERF error rate was
      dependent on correlation and strength of each individual tree where correlation
      is directly proportional to forest error rate and strength is inversely
      proportional to the forest rate. In total, two individual and three integrated
      classification models are developed to achieve enhanced predictions for the liver
      disease types. Analysis of results showed that the proposed framework achieved
      better outcomes in terms of accuracy, true positive rate, precision, F-measure,
      kappa statistic, mean absolute error, and root mean squared error. Furthermore,
      it achieved the highest accuracy rates when compared with the state-of-the-art
      techniques. Results also indicated that the weighted distance function employed
      in EHC has improved the efficiency of proposed system and has shown the
      capability to be used by physicians for diagnostic advice.

PMID- 29599941
TI  - Systems and WBANs for Controlling Obesity.
AB  - According to World Health Organization (WHO) estimations, one out of five adults
      worldwide will be obese by 2025. Worldwide obesity has doubled since 1980. In
      fact, more than 1.9 billion adults (39%) of 18 years and older were overweight
      and over 600 million (13%) of these were obese in 2014. 42 million children under
      the age of five were overweight or obese in 2014. Obesity is a top public health
      problem due to its associated morbidity and mortality. This paper reviews the
      main techniques to measure the level of obesity and body fat percentage, and
      explains the complications that can carry to the individual's quality of life,
      longevity and the significant cost of healthcare systems. Researchers and
      developers are adapting the existing technology, as intelligent phones or some
      wearable gadgets to be used for controlling obesity. They include the promoting
      of healthy eating culture and adopting the physical activity lifestyle. The paper
      also shows a comprehensive study of the most used mobile applications and
      Wireless Body Area Networks focused on controlling the obesity and overweight.
      Finally, this paper proposes an intelligent architecture that takes into account
      both, physiological and cognitive aspects to reduce the degree of obesity and
      overweight.

PMID- 29599942
TI  - Impact of Fitness Status on the Optically Measured Hemodynamic Indexes.
AB  - The physiological characteristics of skin blood flow can be described in terms of
      the hemodynamic indices (HI). The HI is derived from the laser speckle
      characteristics, which are governed by the cutaneous blood flow. A miniaturized
      dynamic light-scattering sensor was used to measure the speckle pattern from the
      finger root. Three groups of subjects from 15 to 25 years of age were tested. The
      first group included subjects who are actively engaged in sport activities; the
      second group included subjects with low level of physical activity; and the third
      group included healthy controls with moderate physical activity. The HI
      parameters were measured prior to and after the performance of a determined
      physical load. As a marker of cardiovascular fitness (CVF), we used the postload
      decay rate of HI. We found that the hemodynamic response to the physical load
      provides a statistically significant correlation with the postload heart rate
      decay. It was also found that postocclusion increase of the arterial HI is more
      prominent in the group with higher physical activity. These results indicate that
      hemodynamic indices can be used as an additional marker for cardiovascular
      fitness level.

PMID- 29599943
TI  - Outlier Removal in Model-Based Missing Value Imputation for Medical Datasets.
AB  - Many real-world medical datasets contain some proportion of missing (attribute)
      values. In general, missing value imputation can be performed to solve this
      problem, which is to provide estimations for the missing values by a reasoning
      process based on the (complete) observed data. However, if the observed data
      contain some noisy information or outliers, the estimations of the missing values
      may not be reliable or may even be quite different from the real values. The aim
      of this paper is to examine whether a combination of instance selection from the
      observed data and missing value imputation offers better performance than
      performing missing value imputation alone. In particular, three instance
      selection algorithms, DROP3, GA, and IB3, and three imputation algorithms, KNNI,
      MLP, and SVM, are used in order to find out the best combination. The
      experimental results show that that performing instance selection can have a
      positive impact on missing value imputation over the numerical data type of
      medical datasets, and specific combinations of instance selection and imputation
      methods can improve the imputation results over the mixed data type of medical
      datasets. However, instance selection does not have a definitely positive impact
      on the imputation result for categorical medical datasets.

PMID- 29599944
TI  - A Novel Sleep Respiratory Rate Detection Method for Obstructive Sleep Apnea Based
      on Characteristic Moment Waveform.
AB  - Obstructive sleep apnea (OSA) affecting human's health is a kind of major
      breathing-related sleep disorders and sometimes leads to nocturnal death.
      Respiratory rate (RR) of a sleep breathing sound signal is an important human
      vital sign for OSA monitoring during whole-night sleeping. A novel sleep
      respiratory rate detection with high computational speed based on characteristic
      moment waveform (CMW) method is proposed in this paper. A portable and wearable
      sound device is used to acquire the breathing sound signal. And the amplitude
      contrast decreasing has been done first. Then, the CMW is extracted with suitable
      time scale parameters, and the sleep RR value is calculated by the extreme points
      of CMW. Experiments of one OSA case and five healthy cases are tested to validate
      the efficiency of the proposed sleep RR detection method. According to manual
      counting, sleep RR can be detected accurately by the proposed method. In
      addition, the apnea sections can be detected by the sleep RR values with a given
      threshold, and the time duration of the segmentation of the breath can be
      calculated for detailed evaluation of the state of OSA. The proposed method is
      meaningful for continued research on the sleep breathing sound signal.

PMID- 29599945
TI  - A Digital Compressed Sensing-Based Energy-Efficient Single-Spot Bluetooth ECG
      Node.
AB  - Energy efficiency is still the obstacle for long-term real-time wireless ECG
      monitoring. In this paper, a digital compressed sensing- (CS-) based single-spot
      Bluetooth ECG node is proposed to deal with the challenge in wireless ECG
      application. A periodic sleep/wake-up scheme and a CS-based compression algorithm
      are implemented in a node, which consists of ultra-low-power analog front-end,
      microcontroller, Bluetooth 4.0 communication module, and so forth. The efficiency
      improvement and the node's specifics are evidenced by the experiments using the
      ECG signals sampled by the proposed node under daily activities of lay, sit,
      stand, walk, and run. Under using sparse binary matrix (SBM), block sparse
      Bayesian learning (BSBL) method, and discrete cosine transform (DCT) basis, all
      ECG signals were essentially undistorted recovered with root-mean-square
      differences (PRDs) which are less than 6%. The proposed sleep/wake-up scheme and
      data compression can reduce the airtime over energy-hungry wireless links, the
      energy consumption of proposed node is 6.53 mJ, and the energy consumption of
      radio decreases 77.37%. Moreover, the energy consumption increase caused by CS
      code execution is negligible, which is 1.3% of the total energy consumption.

PMID- 29599946
TI  - Organic Boundary Location Based on Color-Texture of Visual Perception in Wireless
      Capsule Endoscopy Video.
AB  - This paper addresses the problem of automatically locating the boundary between
      the stomach and the small intestine (the pylorus) in wireless capsule endoscopy
      (WCE) video. For efficient image segmentation, the color-saliency region
      detection (CSD) method is developed for obtaining the potentially valid region of
      the frame (VROF). To improve the accuracy of locating the pylorus, we design the
      Monitor-Judge model. On the one hand, the color-texture fusion feature of visual
      perception (CTVP) is constructed by grey level cooccurrence matrix (GLCM) feature
      from the maximum moments of the phase congruency covariance and hue-saturation
      histogram feature in HSI color space. On the other hand, support vector machine
      (SVM) classifier with the CTVP feature is utilized to locate the pylorus. The
      experimental results on 30 real WCE videos demonstrate that the proposed location
      method outperforms the related valuable techniques.

PMID- 29599947
TI  - An Elderly Care System Based on Multiple Information Fusion.
AB  - With the development of social economy in the 21st century, and the rising of
      medical level, the aging of population have become a global trend. However lots
      of elderly people are in "empty nest" state. In order to solve the problem of
      high risk of daily life in this group, this paper proposed a method to integrate
      the information of video images, sound, infrared, pulse, and other information
      into the elderly care system. The whole system consists of four major components,
      that is, the main control board, the information acquisition boards, the server,
      and the client. The control board receives, processes and analyzes the data
      collected by the information acquisition boards, and uploads necessary
      information to the server, which are to be saved to the database. When something
      unexpected occurs to the elderly, the system will notify the relatives through
      the GPRS (general packet radio service) module. The system also provides an
      interface for the relatives to inquire the living status of the elderly through
      an app. The system can monitor the living status for the elderly with the
      characteristics of quick response, high accuracy, and low cost and can be widely
      applied to the elderly care at home.

PMID- 29599948
TI  - Modelling and Experiment Based on a Navigation System for a Cranio-Maxillofacial
      Surgical Robot.
AB  - In view of the characteristics of high risk and high accuracy in cranio
      maxillofacial surgery, we present a novel surgical robot system that can be used
      in a variety of surgeries. The surgical robot system can assist surgeons in
      completing biopsy of skull base lesions, radiofrequency thermocoagulation of the
      trigeminal ganglion, and radioactive particle implantation of skull base
      malignant tumors. This paper focuses on modelling and experimental analyses of
      the robot system based on navigation technology. Firstly, the transformation
      relationship between the subsystems is realized based on the quaternion and the
      iterative closest point registration algorithm. The hand-eye coordination model
      based on optical navigation is established to control the end effector of the
      robot moving to the target position along the planning path. The closed-loop
      control method, "kinematics + optics" hybrid motion control method, is presented
      to improve the positioning accuracy of the system. Secondly, the accuracy of the
      system model was tested by model experiments. And the feasibility of the closed
      loop control method was verified by comparing the positioning accuracy before and
      after the application of the method. Finally, the skull model experiments were
      performed to evaluate the function of the surgical robot system. The results
      validate its feasibility and are consistent with the preoperative surgical
      planning.

PMID- 29599949
TI  - A New Remote Health-Care System Based on Moving Robot Intended for the Elderly at
      Home.
AB  - Nowadays, due to the growing need for remote care and the constantly increasing
      popularity of mobile devices, a large amount of mobile applications for remote
      care support has been developed. Although mobile phones are very suitable for
      young people, there are still many problems related to remote health care of the
      elderly. Due to hearing loss or limited movements, it is difficult for the
      elderly to contact their families or doctors via real-time video call. In this
      paper, we introduce a new remote health-care system based on moving robots
      intended for the elderly at home. Since the proposed system is an online system,
      the elderly can contact their families and doctors quickly anytime and anywhere.
      Besides call, our system involves the accurate indoor object detection algorithms
      and automatic health data collection, which are not included in existing remote
      care systems. Therefore, the proposed system solves some challenging problems
      related to the elderly care. The experiment has shown that the proposed care
      system achieves excellent performance and provides good user experience.

PMID- 29599950
TI  - Real-Time EEG Signal Enhancement Using Canonical Correlation Analysis and
      Gaussian Mixture Clustering.
AB  - Electroencephalogram (EEG) signals are usually contaminated with various
      artifacts, such as signal associated with muscle activity, eye movement, and body
      motion, which have a noncerebral origin. The amplitude of such artifacts is
      larger than that of the electrical activity of the brain, so they mask the
      cortical signals of interest, resulting in biased analysis and interpretation.
      Several blind source separation methods have been developed to remove artifacts
      from the EEG recordings. However, the iterative process for measuring separation
      within multichannel recordings is computationally intractable. Moreover, manually
      excluding the artifact components requires a time-consuming offline process. This
      work proposes a real-time artifact removal algorithm that is based on canonical
      correlation analysis (CCA), feature extraction, and the Gaussian mixture model
      (GMM) to improve the quality of EEG signals. The CCA was used to decompose EEG
      signals into components followed by feature extraction to extract representative
      features and GMM to cluster these features into groups to recognize and remove
      artifacts. The feasibility of the proposed algorithm was demonstrated by
      effectively removing artifacts caused by blinks, head/body movement, and chewing
      from EEG recordings while preserving the temporal and spectral characteristics of
      the signals that are important to cognitive research.

PMID- 29599951
TI  - Leukocyte Image Segmentation Using Novel Saliency Detection Based on Positive
      Feedback of Visual Perception.
AB  - This paper presents a novel method for salient object detection in nature image
      by simulating microsaccades in fixational eye movements. Due to a nucleated cell
      usually stained that is salient obviously, the proposed method is suitable to
      segment nucleated cell. Firstly, the existing fixation prediction method is
      utilized to produce an initial fixation area. Followed EPELM (ensemble of
      polyharmonic extreme learning machine) is trained on-line by the pixels sampling
      from the fixation and nonfixation area. Then the model of EPELM could be used to
      classify image pixels to form new binary fixation area. Depending upon the
      updated fixation area, the procedure of "pixel sampling-learning-classification"
      could be performed iteratively. If the previous binary fixation area and the
      latter one were similar enough in iteration, it indicates that the perception is
      saturated and the loop should be terminated. The binary output in iteration could
      be regarded as a kind of visual stimulation. So the multiple outputs of visual
      stimuli can be accumulated to form a new saliency map. Experiments on three image
      databases show the validity of our method. It can segment nucleated cells
      successfully in different imaging conditions.

PMID- 29599952
TI  - Optical Design with Narrow-Band Imaging for a Capsule Endoscope.
AB  - The study proposes narrow-band imaging (NBI) lens design of 415 nm and 540 nm of
      a capsule endoscope (CE). The researches show that in terms of the rate of
      accuracy in detecting and screening neoplastic and nonneoplastic intestinal
      lesions, the NBI system outperformed that of traditional endoscopes and rivaled
      that of chromoendoscopes. In the proposed NBI CE optical system, the simulation
      result shows the field of view (FOV) was 109.8 degrees ; the modulation transfer
      function (MTF) could achieve 12.5% at 285 lp/mm and 34.1% at 144 lp/mm. The
      relative illumination reaches more than 60%, and the system total length was less
      than 4 mm. Finally, this design provides high-quality images for a 300-megapixel
      1/4" CMOS image sensor with a pixel size of 1.75 MUm.

PMID- 29599953
TI  - Intelligent Control Wheelchair Using a New Visual Joystick.
AB  - A new control system of a hand gesture-controlled wheelchair (EWC) is proposed.
      This smart control device is suitable for a large number of patients who cannot
      manipulate a standard joystick wheelchair. The movement control system uses a
      camera fixed on the wheelchair. The patient's hand movements are recognized using
      a visual recognition algorithm and artificial intelligence software; the derived
      corresponding signals are thus used to control the EWC in real time. One of the
      main features of this control technique is that it allows the patient to drive
      the wheelchair with a variable speed similar to that of a standard joystick. The
      designed device "hand gesture-controlled wheelchair" is performed at low cost and
      has been tested on real patients and exhibits good results. Before testing the
      proposed control device, we have created a three-dimensional environment
      simulator to test its performances with extreme security. These tests were
      performed on real patients with diverse hand pathologies in Mohamed Kassab
      National Institute of Orthopedics, Physical and Functional Rehabilitation
      Hospital of Tunis, and the validity of this intelligent control system had been
      proved.

PMID- 29599954
TI  - Efficient OCT Image Enhancement Based on Collaborative Shock Filtering.
AB  - Efficient enhancement of noisy optical coherence tomography (OCT) images is a key
      task for interpreting them correctly. In this paper, to better enhance details
      and layered structures of a human retina image, we propose a collaborative shock
      filtering for OCT image denoising and enhancement. Noisy OCT image is first
      denoised by a collaborative filtering method with new similarity measure, and
      then the denoised image is sharpened by a shock-type filtering for edge and
      detail enhancement. For dim OCT images, in order to improve image contrast for
      the detection of tiny lesions, a gamma transformation is first used to enhance
      the images within proper gray levels. The proposed method integrating image
      smoothing and sharpening simultaneously obtains better visual results in
      experiments.

PMID- 29599955
TI  - Enhancement of the Comb Filtering Selectivity Using Iterative Moving Average for
      Periodic Waveform and Harmonic Elimination.
AB  - A recurring problem regarding the use of conventional comb filter approaches for
      elimination of periodic waveforms is the degree of selectivity achieved by the
      filtering process. Some applications, such as the gradient artefact correction in
      EEG recordings during coregistered EEG-fMRI, require a highly selective comb
      filtering that provides effective attenuation in the stopbands and gain close to
      unity in the pass-bands. In this paper, we present a novel comb filtering
      implementation whereby the iterative filtering application of FIR moving average
      based approaches is exploited in order to enhance the comb filtering selectivity.
      Our results indicate that the proposed approach can be used to effectively
      approximate the FIR moving average filter characteristics to those of an ideal
      filter. A cascaded implementation using the proposed approach shows to further
      increase the attenuation in the filter stopbands. Moreover, broadening of the
      bandwidth of the comb filtering stopbands around -3 dB according to the
      fundamental frequency of the stopband can be achieved by the novel method, which
      constitutes an important characteristic to account for broadening of the harmonic
      gradient artefact spectral lines. In parallel, the proposed filtering
      implementation can also be used to design a novel notch filtering approach with
      enhanced selectivity as well.

PMID- 29599956
TI  - Advancements of Image Processing and Vision in Healthcare.

PMID- 29599957
TI  - A Comprehensive Method for Accurate Strain Distribution Measurement of Cell
      Substrate Subjected to Large Deformation.
AB  - Cell mechanical stretching in vitro is a fundamental technique commonly used in
      cardiovascular mechanobiology research. Accordingly, it is crucial to measure the
      accurate strain field of cell substrate under different strains. Digital image
      correlation (DIC) is a widely used measurement technique, which is able to obtain
      the accurate displacement and strain distribution. However, the traditional DIC
      algorithm used in digital image correlation engine (DICe) cannot obtain accurate
      result when utilized in large strain measurement. In this paper, an improved
      method aiming to acquire accurate strain distribution of substrate in large
      deformation was proposed, to evaluate the effect and accuracy, based on numerical
      experiments. The results showed that this method was effective and highly
      accurate. Then, we carried out uniaxial substrate stretching experiments and
      applied our method to measure strain distribution of the substrate. The proposed
      method could obtain accurate strain distribution of substrate film during large
      stretching, which would allow researchers to adequately describe the response of
      cells to different strains of substrate.

PMID- 29599958
TI  - Vision Diagnostics and Treatment System for Children with Disabilities.
AB  - Vision plays a crucial role in children's mental development. Therefore, early
      diagnosis of any vision disparities and implementation of a correct therapy is
      very important. However, carrying out such a procedure in case of young children
      and especially children with brain dysfunctions poses some limitations due to
      cooperation problems. The vision diagnostics and treatment (VisDaT) system
      presented in this paper is meant to help therapists in proper diagnosis and
      treatment involving such children. It utilizes a computer connected to two
      monitors and equipped with a specialized software. The main system components are
      as follows: an eye tracker recording child's eye movements and a digital camera
      monitoring online child's reactions. The system is equipped with a specialized
      software, which creates the opportunity to stimulate children's vision with a
      dedicated stimulus and post hoc analyses of recorded sessions, which enable
      making decision as to the future treatment.

PMID- 29599959
TI  - Assisted Protection Headphone Proposal to Prevent Chronic Exposure to Percussion
      Instruments on Musicians.
AB  - The effects of chronic exposure to high sound pressure levels (SPLs) are widely
      studied in the industry environment. However, the way that SPLs affect music
      students has not been thoroughly examined. In this paper, we study the SPL
      exposure of batucada students and we propose an assisted protection headphone as
      a part of e-health system. We measured the SPL reached during a regular
      percussion class. Pure-tone audiometries were performed to a set of percussion
      students. The gathered data were statistically analyzed. The assisted protection
      headphones and their operation are detailed and tested during a regular class.
      Our results show that 35% of the musicians present with a noise-induced hearing
      loss, considered as two frequencies with hearing loss of 25 dB or more or one
      frequency with a hearing loss of 30 dB or more. Our data also shows that those
      students that do not use any protection have a greater hearing loss. However, the
      students that use protection headphones are also suffering hearing loss. There
      might be a problem in the way that musicians are using the protection headphones.
      Our assisted protection headphones as a part of e-health measures can diminish
      the negative effects of percussion instruments for musicians.

PMID- 29599960
TI  - Association between maternal antidepressant use during pregnancy and autism
      spectrum disorder: an updated meta-analysis.
AB  - Studies have investigated the risk of autism spectrum disorder (ASD) in children
      exposed in utero to antidepressant, with inconsistent results. Given the
      substantial public health implications on this topic, here, we presented an
      updated meta-analysis of the association between maternal antidepressant use
      during pregnancy and ASD. Cochrane Library, EMBASE, PsycINFO, and PubMed
      databases were systematically searched. A random effects model was used to pool
      the adjusted relative risk (RR) for cohort studies and the adjusted odds ratio
      (OR) for case-control studies as well as their corresponding 95% confidence
      intervals (CIs). Meta-analysis restricted to sibling studies was also conducted.
      Publication bias was systematically assessed. Fourteen studies were identified
      (eight cohort studies and six case-control studies). Pooled adjusted RR for
      cohort studies (n = 2,839,980) was 1.13 (0.93-1.39) showed a non-significant
      association; while two studies were potentially missing from the test of
      publication bias, filled estimates also showed a non-significant association
      (filled RR 0.97, 95% CI 0.79-1.19). Pooled OR was 1.51 (1.15-1.99) for case
      control studies (n = 117,737) showed a significant association; two studies were
      potentially missing; however, the filled estimates suggested a non-significant
      association (filled OR 1.26, 95% CI 0.98-1.62). Analyses restricted to sibling
      studies also showed a non-significant association (RR 0.99, 95% CI 0.81-1.22). In
      summary, we did not evidence a significant association between maternal
      antidepressant use during pregnancy and ASD.

PMID- 29599961
TI  - Idiopathic omental infarction: One for conservative or surgical management?
AB  - Idiopathic omental infarction (IOI) is a rare cause of right-sided abdominal
      pain, mimicking serious surgical pathology. It occurs in <4 in 1000 cases of
      appendicitis. IOI can be a challenge to diagnose, as features may mimic
      appendicitis, and therefore in young patients, may only be discovered on
      laparoscopy. CT features can be diagnostic, but due to its rarity the diagnosis
      may be unclear. The literature supports both conservative management and surgical
      management (to expedite symptom resolution). We present a case of IOI and discuss
      our management and learning from the case. We discuss the utility of CT
      radiology, conservative management and the benefits of non-resection management,
      even at laparoscopy.

PMID- 29599962
TI  - Brown bowel syndrome, an unusual cause of sigmoid volvulus.
AB  - We report a case of a 79-year-old gentleman who presented to the emergency
      department with a 5-day history of abdominal pain, constipation, a progressively
      distending abdomen and new onset feculent vomiting on a background of a recent
      endoscopic decompression of a sigmoid volvulus. Investigations confirmed the
      presence of a recurrent sigmoid volvulus. Attempts to reduce this endoscopically
      failed and laparotomy with sub-total colectomy and ileostomy formation was
      performed. Histology from the resected specimen identified a distinct pathology,
      namely intestinal lipofuscinosis also known as brown bowel syndrome. Brown bowel
      syndrome is a recognized but rare complication of chronic long term malnutrition.
      It may present in a myriad of ways including atonia and, rarely, massive colonic
      dilatation, as in our case.

PMID- 29599963
TI  - Laparoscopic resection of a giant retroperitoneal melanotic schwannoma.
AB  - Background: Retroperitoneal schwannomas are extremely rare, as they account for
      only 3% of retroperitoneal tumors. Clinical symptoms are nonspecific and of late
      onset, meaning that these tumors are diagnosed at an advanced stage. Surgical
      resection is required for histological diagnosis and to prevent possible
      malignant transformation. Celioscopy offers numerous benefits, reducing
      postoperative pain and speeding up the patient's return to autonomy, but it can
      pose a real challenge due to the size of these lesions. Case presentation: We
      report a case of laparoscopic resection of a very large right-sided
      retroperitoneal schwannoma, with a particular histological form. Conclusion:
      Surgical resection in a single unit remains the golden rule, and a laparoscopy
      can be proposed when the diagnosis is beyond doubt. The large size of the
      retroperitoneal melanotic schwannomas, a common feature, increases surgical
      difficulties but is not a contraindication to this approach.

PMID- 29599965
TI  - Airborne protein concentration: a key metric for type 1 allergy risk assessment
      in home measurement challenges and considerations.
AB  - Background: Exposure to airborne proteins can be associated with the development
      of immediate, IgE-mediated respiratory allergies, with genetic, epigenetic and
      environmental factors also playing a role in determining the likelihood that
      sensitisation will be induced. The main objective of this study was to determine
      whether airborne concentrations of selected common aeroallergens could be
      quantified in the air of homes using easily deployable, commercially available
      equipment and analytical methods, at low levels relevant to risk assessment of
      the potential to develop respiratory allergies. Additionally, air and dust
      sampling were compared and the influence of factors such as different filter
      types on allergen quantification explored. Methods: Low volume air sampling pumps
      and DUSTREAM(r) dust samplers were used to sample 20 homes and allergen levels
      were quantified using a MARIA(r) immunoassay. Results: It proved possible to
      detect a range of common aeroallergens in the home with sufficient sensitivity to
      quantify airborne concentrations in ranges relevant to risk assessment (Limits of
      Detection of 0.005-0.03 ng/m3). The methodology discriminates between homes
      related to pet ownership and there were clear advantages to sampling air over
      dust which are described in this paper. Furthermore, in an adsorption-extraction
      study, PTFE (polytetrafluoroethylene) filters gave higher and more consistent
      recovery values than glass fibre (grade A) filters for the range of aeroallergens
      studied. Conclusions: Very low airborne concentrations of allergenic proteins in
      home settings can be successfully quantified using commercially available pumps
      and immunoassays. Considering the greater relevance of air sampling to human
      exposure of the respiratory tract and its other advantages, wider use of
      standardised, sensitive techniques to measure low airborne protein concentrations
      and how they influence development of allergic sensitisation and symptoms could
      accelerate our understanding of human dose-response relationships and refine our
      knowledge of thresholds of allergic sensitisation and elicitation via the
      respiratory tract.

PMID- 29599964
TI  - Syncytium calcium signaling and macrophage function in the heart.
AB  - Macrophages are traditionally viewed as a key component of the immunity defense
      system. Recent studies have identified resident macrophages in multiple organs
      including the heart, in which the cells perform their crucial role on tissue
      repair after myocardial infarction (MI). The cardiac-specific macrophages
      interdigitate with cardiomyocytes particularly at the atrioventricular node
      region. The integrative communication between macrophage and cardiomyocytes can
      modulate the contractile function of the heart. Coordinated control of
      intracellular calcium signaling and intercellular electrical conduction via the
      syncytium network underlie the synchronized beating of the heart. In this review
      article, we introduce the concept the syncytium calcium signaling in the
      cardiomyocytes can modulate gene expression in the resident macrophages and their
      integration with the cardiomyocytes. The cardiac macrophages originate from bone
      marrow stem cells, migrate to local via vessel, and settle down as a
      naturalization process in heart. As the macrophages perform on regulating
      electrical conduction, and accomplish post MI non-scared completed regeneration
      or partial regeneration with fibrotic scar at different stage of postnatal
      development, we understand that multiple functions of cardiac macrophage should
      carry on with diverse linages. The naturalization process in heart of macrophages
      to the cardiomyocytes serves important roles to control of electrical signaling
      and calcium-dependent contractile function of the heart.

PMID- 29599967
TI  - Prevalence of welfare outcomes in the weaner and finisher stages of the
      production cycle on 31 Irish pig farms.
AB  - Background: Knowledge on the most prevalent welfare problems for pigs in
      different production stages is required to improve herd management plans. Thirty
      one farrow-to-finish pig farms were visited between July and November 2015 to
      assess the welfare of pigs using the multicriteria approach of the Welfare
      Quality(r) protocol. On each farm, 6 pens were selected using proportionate
      stratified sampling in the first weaner (S1, 4 to 8 wks), second weaner (S2, 8 to
      13 wks) and finisher stage (S3, 13 to 23 wks), excluding hospital pens. Each pen
      was observed for 10 min and the number of pigs affected by different welfare
      outcomes was recorded. The percentage of pigs affected was calculated and ranked
      to identify the most prevalent outcomes within each production stage. Differences
      between production stages were analysed using generalised linear mixed models for
      binomial data with pen within stage and farm as a random effect. Results: Tail
      and ear lesions showed the highest prevalence; however, large variation was
      observed between farms. In S1 the most prevalent welfare outcomes (presented as
      median prevalence) were poor body condition (4.4%), lethargic pigs (1.5%),
      scouring (20.3% of pens) and huddling (3.7%). In S2 and S3 outcomes related to
      injurious behaviour (tail lesions: 5.9% [S2] and 10.5% [S3], ear lesions: 9.1%
      [S2] and 3.3% [S3], and flank lesions: 0.4% [S2] and 1.3% [S3]), lameness (0.8%
      [S2] and 1.1% [S3]), bursitis (3.9% [S2] and 7.5% [S3]) and hernias (1.6% [S2]
      and 1.8% [S3]) were more prevalent. Conclusions: A large variation was observed
      for the recorded welfare outcomes corresponding to the different challenges pigs
      experience during the different stages of production on commercial pig farms. The
      prevalence of pigs affected by lesions caused by injurious behavior is a cause
      for concern and requires a collaborative approach to identify appropriate
      intervention strategies. This information could be used to further investigate
      appropriate benchmark values for different welfare outcomes that would assist the
      pig industry to develop appropriate health and welfare management plans to
      minimise welfare problems. At herd level such plans should include information on
      aspects of intervention, treatment, and the management of hospital pens as well
      as euthanasia.

PMID- 29599966
TI  - Effectiveness of icatibant for treatment of hereditary angioedema attacks is not
      affected by body weight: findings from the Icatibant Outcome Survey, a cohort
      observational study.
AB  - Background: Icatibant is a bradykinin B2-receptor antagonist used for the
      treatment of hereditary angioedema attacks resulting from C1-inhibitor
      deficiency. Treatment is not adjusted by body weight however the impact of body
      mass index (BMI) on the effectiveness of icatibant is not documented in the
      literature. We examined disease characteristics and icatibant treatment
      effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an
      ongoing, international, observational study monitoring the real-world safety and
      effectiveness of icatibant. Methods: Attack and treatment characteristics as well
      as outcomes following treatment with icatibant were compared among patients with
      underweight, normal, overweight, and obese BMI. Results: Data from 2697 icatibant
      treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of
      underweight, normal, overweight, and obese BMI, respectively) were analyzed.
      There was no significant difference in the frequency and severity of attacks
      across BMI groups, although obese patients tended to have more attacks of high
      severity. There was no impact of BMI on the frequency of laryngeal attacks, but
      patients with normal BMI had fewer cutaneous attacks and more abdominal attacks.
      Most attacks (71.9-83.8%) were treated with a single icatibant injection without
      the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of
      BMI. Patients with obese BMI used pdC1-INH as rescue treatment more often (P <
      0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than
      patients with normal BMI (P = 0.007). Furthermore, time to resolution and
      duration of attack were shorter for patients with high BMI (P < 0.001 for
      overweight and P < 0.05 for obese versus normal). Conclusion: Overall, icatibant
      was comparatively effective in treating attacks in patients across all BMI
      groups.Trial registration NCT01034969.

PMID- 29599968
TI  - Partial avulsion of the ulnaris lateralis and enthesiopathy of the lateral
      epicondyle of the humerus in a thoroughbred race horse.
AB  - Background: There is relatively little literature on elbow disease in the horse.
      The only published reports on soft tissue conditions describe collateral ligament
      and biceps brachii injuries. Case presentation: A three-year old Thoroughbred
      gelding presented with a history of acute onset right forelimb lameness of less
      than one week duration, one month after commencing training in a National Hunt
      racing yard. Physical examination and peri-neural anaesthesia failed to localise
      the lesion. Lameness was localised to the distal humerus by nuclear scintigraphy
      and intra-articular anaesthesia. A partial avulsion of the tendinous origin of
      the ulnaris lateralis and enthesiopathy of the lateral humeral epicondyle was
      diagnosed on ultrasonography. Ultrasonographic findings were loss of longitudinal
      fibre pattern, a discrete hypo-echoic region within the ulnaris lateralis tendon
      of origin, and remodelling of the lateral epicondyle of the right humerus at the
      site of the origin of the ulnaris lateralis. No abnormalities were identified on
      radiography. The lameness did not resolve with rest, but was successfully treated
      with extra corporal shockwave therapy (ECSWT) and intra-lesional corticosteroid
      injections. Conclusion: This is the first report of partial avulsion of the
      ulnaris lateralis and enthesiopathy of the lateral humeral epicondyle in the
      horse. In contrast to other reported soft tissue conditions of the elbow, this
      horse had a successful return to work. This case highlights the value of
      ultrasonography in assessing peri-articular soft tissues, and the importance of
      pain relief as treatment in some soft tissue injuries.

PMID- 29599969
TI  - Healthcare-associated fungal outbreaks: New and uncommon species, New molecular
      tools for investigation and prevention.
AB  - Outbreaks of healthcare-associated fungal infections have repeatedly been
      described over recent years, often caused by new or uncommon species. Candida
      auris, a recently described multidrug-resistant yeast species, is certainly the
      most worrisome species having caused several severe healthcare outbreaks of
      invasive infections, on four continents. Also, large nosocomial outbreaks due to
      uncommon fungal species such as Exserohilum rostratum and Sarocladium kiliense,
      were both linked to contamination of medical products, however the source of
      another outbreak, caused by Saprochaete clavata, remains unresolved. Furthermore,
      these outbreaks identified new populations under threat in addition to those
      commonly at risk for invasive fungal infections, such as immunosuppressed and
      intensive care unit patients. All of these outbreaks have highlighted the
      usefulness of a high level of awareness, rapid diagnostic methods, and new
      molecular typing tools such as Whole Genome Sequencing (WGS), prompt
      investigation and aggressive interventions, including notification of public
      health agencies. This review summarizes the epidemiological and clinical data of
      the majority of healthcare-associated outbreaks reported over the last 6 years
      caused by uncommon or new fungal pathogens, as well as the contribution of WGS as
      support to investigate the source of infection and the most frequent control
      measures used.

PMID- 29599970
TI  - Medication practice in hospitals: are nanosimilars evaluated and substituted
      correctly?
AB  - Introduction: This study investigates the drug selection and dispensing behaviour
      of hospital pharmacists of intravenous iron products including iron sucrose and
      iron sucrose similar, with special emphasis on substitution and
      interchangeability in France and Spain. Iron-carbohydrate complex drugs represent
      different available intravenous iron drugs and are part of the non-biological
      complex drug (NBCD) class, an expanding drug class with up to 30 brands available
      in intravenous pharmacotherapy and over 50 in clinical development. Follow-on
      versions of iron sucrose have appeared in some markets such as France and Spain,
      which were authorised by the generic approval pathway. However, differences in
      clinical efficacy and safety of iron sucrose similars compared with the reference
      originator drug Venofer have been observed, putting a question mark on their
      equivalence as assessed for authorisation and consequently their substitutability
      and interchangeability. Method: 70 French and 70 Spanish hospital pharmacists
      were surveyed via an online questionnaire on their formulary selection and
      dispensing behaviour of intravenous iron medicines. Results: There is little
      awareness about the characteristics of this class of drugs and the reported
      differences in safety and efficacy between iron sucrose and iron sucrose
      similars. In approximately 85% of cases the intravenous iron is chosen according
      to the hospital formulary. In 30% (France) and 34% (Spain) of cases an iron
      sucrose similar was dispensed because the formulary requires dispensing an
      alternative lower cost drug when available. In 26% (France) and 52% (Spain) of
      cases the physician is not informed on such a medication change using a similar
      product. Conclusions: Evaluation of NBCD similars for substitution and
      interchange by hospital pharmacists is rarely based on scientific and clinical
      criteria but rather on cost aspects only, which does not ensure safe, efficacious
      and cost-effective use of such drugs.

PMID- 29599971
TI  - Time and age trends in morning and evening protein intakes of German children and
      adolescents.
AB  - The present study describes time and age trends in morning and evening protein
      intakes and sources among German children and adolescents from 1985 to 2014. A
      total of 9757 three-day weighed dietary records of 1246 3- to 18-year-old
      participants of the Dortmund Nutritional and Anthropometric Longitudinally
      Designed (DONALD) study were analysed using polynomial mixed-effects regression
      models. Morning protein intake increased over the study period by approximately 1
      % of morning energy intake (linear trend P < 0.0001), with the youngest and the
      oldest children having the highest protein intake (linear, quadratic trend P <
      0.0001). Evening protein intake increased over time by approximately 2 % of
      evening energy intake in girls (linear trend P < 0.0001) and 1 % of evening
      energy intake in boys (quadratic trend P = 0.0313), with decreasing intake with
      age (girls: linear trend P < 0.0001; boys: linear trend P = 0.0963). Time trends
      were largely due to increases in protein from 'starchy foods'. In conclusion,
      morning and evening protein intakes increased modestly between 1985 and 2014;
      these increases were, however, not accompanied by increases in traditional
      protein sources (i.e. meat or dairy products).

PMID- 29599972
TI  - Effects of fish and krill oil on gene expression in peripheral blood mononuclear
      cells and circulating markers of inflammation: a randomised controlled trial.
AB  - Marine n-3 (omega-3) fatty acids alter gene expression by regulating the activity
      of transcription factors. Krill oil is a source of marine n-3 fatty acids that
      has been shown to modulate gene expression in animal studies; however, the effect
      in humans is not known. Hence, we aimed to compare the effect of intake of krill
      oil, lean and fatty fish with a similar content of n-3 fatty acids, and high
      oleic sunflower oil (HOSO) with added astaxanthin on the expression of genes
      involved in glucose and lipid metabolism and inflammation in peripheral blood
      mononuclear cells (PBMC) as well as circulating inflammatory markers. In an 8
      week trial, healthy men and women aged 18-70 years with fasting TAG of 1.3-4.0
      mmol/l were randomised to receive krill oil capsules (n 12), HOSO capsules (n 12)
      or lean and fatty fish (n 12). The weekly intakes of marine n-3 fatty acids from
      the interventions were 4654, 0 and 4103 mg, respectively. The mRNA expression of
      four genes, PPAR gamma coactivator 1A (PPARGC1A), steaoryl-CoA desaturase (SCD),
      ATP binding cassette A1 (ABCA1) and cluster of differentiation 40 (CD40), were
      differently altered by the interventions. Furthermore, within-group analyses
      revealed that krill oil down-regulated the mRNA expression of thirteen genes,
      including genes involved in glucose and cholesterol metabolism and beta
      oxidation. Fish altered the mRNA expression of four genes and HOSO down-regulated
      sixteen genes, including several inflammation-related genes. There were no
      differences between the groups in circulating inflammatory markers after the
      intervention. In conclusion, the intake of krill oil and HOSO with added
      astaxanthin alter the PBMC mRNA expression of more genes than the intake of fish.

PMID- 29599973
TI  - Effects of Lactobacillus acidophilus on the growth performance and intestinal
      health of broilers challenged with Clostridium perfringens.
AB  - Background: Clostridium perfringens is the main etiological agent of necrotic
      enteritis. Lactobacilli show beneficial effects on intestinal health in
      infectious disease, but the protective functions of lactobacilli in C.
      perfringens-infected chickens are scarcely described. This study examined the
      effects of Lactobacillus acidophilus (L. acidophilus) on the growth performance
      and intestinal health of broiler chickens challenged with Clostridium perfringens
      (C. perfringens) over a 28-day period. Using a 2 * 2 factorial arrangement of
      treatments, a total of 308 1-day-old male Arbor Acres broiler chicks were
      included to investigate the effects of Lactobacillus acidophilus (L. acidophilus)
      on the growth performance and intestinal health of broiler chickens challenged
      with Clostridium perfringens (C. perfringens) during a 28-day trial. Results:
      During infection (d 14-21), C. perfringens challenge decreased the average daily
      gain (P <  0.05), and increased feed conversion ratio and the mortality rate (P <
      0.05). However, dietary supplementation with L. acidophilus increased the body
      weight of C. perfringens-infected broilers on d 21 (P <  0.05), and tended to
      decrease the mortality (P = 0.061). C. perfringens challenge decreased the villus
      height (P <  0.05), the ratio of villus height to crypt depth (P <  0.05) and
      OCLN (occludin) mRNA expression (P <  0.05), and increased the pro-inflammatory
      cytokine expression in the spleen and jejunum, the intestinal populations of C.
      perfringens and Escherichia (P < 0.05), and the serum content of endotoxin (P <
      0.05), regardless of L. acidophilus supplementation. In contrast, dietary L.
      acidophilus reducedthe intestinal lesion score of challenged broilers (P < 0.05),
      the mRNA expression of pro-inflammatory cytokines, ileal populations of
      Escherichia and serum endotoxin content (P < 0.05), but increased the intestinal
      Lactobacillus populations (P < 0.05), irrespective of C. perfringens challenge.
      Conclusion: Dietary addition of L. acidophilus could improve the intestinal
      health and reduce the mortality of broilers suffering from necrotic enteritis.

PMID- 29599974
TI  - Tuberculosis in South Asia: a tide in the affairs of men.
AB  - Background: Tuberculosis (TB) remains the most common cause of infectious disease
      deaths worldwide. What is perhaps less appreciated is that the caseload of
      tuberculosis patients in South Asia is staggering.South Asia has almost 40% of
      the global TB burden with 4,028,165 cases in 2015. This region also has a
      disproportionate share of TB deaths (681,975 deaths, 38% of the global burden).
      Worldwide just 12.5% of TB cases are in HIV positive individuals, but much
      research and investment has focused on HIV-associated TB. Only 3.5% of patients
      with tuberculosis in South Asia have HIV co-infection. Not surprisingly with such
      a huge burden of disease, this region has an estimated 184,336 multi drug
      resistant (MDR) cases among notified TB cases which accounts for a third of
      global MDR burden. Crucially, at least 70% of the estimated MDR cases remain
      untreated in this region and MDR treatment success ranged from only 46% for India
      to 88% for Sri Lanka in the 2012 cohort that received treatment. This region
      represents many of the drivers of the modern TB epidemic: rapid urbanization and
      high density populations with dramatically rising incidence of diabetes, a
      burgeoning and largely unregulated private sector with escalating drug resistance
      and high air pollution both outdoor and household. Conclusion: From bacterial
      biochemistry to policy implementation, we suggest ways in which South Asia can
      seize the opportunity lead global TB elimination by demonstrating feasibility in
      some of the world's most densely populated cities and remotest reaches of the
      Himalayas. Clearly political will is essential, but we cannot defeat TB without
      understanding how to eliminate it in South Asia.

PMID- 29599975
TI  - Exosomes as a novel pathway for regulating development and diseases of the skin.
AB  - Exosomes are one of the most potent intercellular communicators, which are able
      to communicate with adjacent or distant cells. Exosomes deliver various bioactive
      molecules, including membrane receptors, proteins, mRNA and microRNA, to target
      cells and serve roles. Recent studies have demonstrated that exosomes may
      regulate the functions and diseases of the skin, which is the largest organ of
      the human body. The abnormal functions of the skin lead to the progression of
      scleroderma, melanoma, baldness and other diseases. A previous study has
      demonstrated that epithelial progenitor cells are rich in several subunits of
      exosomes that may maintain the proliferative capacity of these epithelial
      progenitor cells, which is essential for the development of the epidermis.
      Exosomes derived from human adipose mesenchymal stem cells accelerate skin wound
      healing by optimizing fibroblast properties; this is beneficial for the recovery
      of postoperative and other wounds. Exosomes derived from adipocytes promote
      melanoma migration and invasion through fatty acid oxidation; therefore, in the
      clinic, it may be possible to improve the prognosis of patients with melanoma by
      reducing their body fat content. Exosomes derived from keratinocytes modulate
      melanocyte pigmentation, which has been utilized as a novel mechanism for the
      regulation of pigmentation in conditions including Moynahan syndrome and
      albinism. Meanwhile, scleroderma patients with vascular abnormalities may
      experience decreased serum exosome levels; it may therefore be possible to detect
      the exosome content in sera in order to diagnose and treat scleroderma. In
      addition, the use of exosomes has been suggested to promote or enhance hair
      growth, which has been demonstrated to be highly effective. These studies have
      provided new opportunities and therapeutic strategies for understanding how
      exosomes regulate intercellular communication in pathological processes of the
      skin.

PMID- 29599976
TI  - High sensitivity 8-color flow cytometry assay for paroxysmal nocturnal
      hemoglobinuria granulocyte and monocyte detections.
AB  - Flow cytometry is the gold standard in diagnosis of paroxysmal nocturnal
      hemoglobinuria (PNH) by detecting the absence of glycol-phosphatidyl inositol
      (GPI)-linked protein expression on granulocyte and monocyte surfaces. However,
      the current assays are not optimized and require improvement, particularly in
      reducing background fluorescence and optimizing sensitivity and specificity. With
      more fluorochromes available and with advances in instrument engineering, rare
      populations may be identified with high sensitivity. The present study assessed
      an 8-color combination of comprehensive GPI-linked markers, namely fluorescein
      labeled proaerolysin (FLAER), cluster of differentiation 157 (CD157), CD24 and
      CD14, and the lineage markers for granulocyte (CD15) and monocyte (CD64) cells to
      detect PNH clones. Additionally, to optimize the PNH flow assay, a 'dump' channel
      was used, comprised of CD5 and CD19, to exclude non-specific binding in order to
      reduce background. This method aimed to improve sensitivity and reduce the
      background to create an optimized PNH flow cocktail. The results demonstrated
      that the current 4-color PNH combination identifies a CD55- and FLAER+ population
      that is not PNH clones. By contrast, the 8-color panel delineated PNH clones from
      both monocyte and granulocytes by using granulocyte antigen (CD15) and monocyte
      antigen (CD64) as a gating strategy. The sensitivity was 0.01% for granulocytes
      and 0.05% for monocytes with an acquisition of 100,000 monocyte and granulocyte
      events. The background on a normal whole blood sample was 0.00076% on monocytes
      and 0.00277% on granulocytes. Thus, overall, the 8-color PNH assay exhibited high
      levels of specificity and sensitivity. The 8-color combination facilitated the
      improvement and enhancement of sensitivity in PNH clone identification, and may
      provide a useful tool for pathologists in PNH diagnosis and for monitoring
      patients at risk of developing classical/hemolytic PNH, to enable treatment to be
      delivered promptly.

PMID- 29599977
TI  - Computer-aided design of temozolomide derivatives based on alkylglycerone
      phosphate synthase structure with isothiocyanate and their
      pharmacokinetic/toxicity prediction and anti-tumor activity in vitro.
AB  - Despite the development of temozolomide (TMZ), a novel type of glioma therapeutic
      drug, malignant glioma remains to cause severe damage to human health. The
      present study aimed to utilize the molecular biological differences between tumor
      and normal cells to design TMZ derivatives with improved selectivity and
      targeting using computer-aided drug design (CADD). Taking alkylglycerone
      phosphate synthase (AGPS) as a target, a 3D structure-activity relationship model
      was built using CADD technology; molecular docking of isothiocyanate (ITC) and
      TMZ compounds was conducted; ITC-TMZ derivatives were designed; and predictions
      on the absorption, distribution, metabolism and excretion (ADME) processes and
      toxicity of the ITC-TMZ derivatives were established in order to obtain improved
      understanding of the structure-activity relationship of the candidate compounds.
      Using these techniques, it was identified that the docking scores of the
      structural derivatives S1-9 were higher than that of TMZ. Additionally, S3, -6, 
      7, -8, -9 and -10 exhibited enhanced ADME and similar toxicity to that of TMZ.
      The half maximal inhibitory concentrations of the CADD derivatives were also
      assessed in the glioma U87MG and U251 cell lines, and the activities of S1, -3, 
      8 and -10 were determined to be greater than that of TMZ, suggesting their
      potential as anti-cancer drugs with adequate AGPS targeting, ADME/toxicity and
      anti-tumor activity.

PMID- 29599979
TI  - The phenotype, psychotype and genotype of bruxism.
AB  - Bruxism is a jaw muscle activity that involves physio-pathological, psycho
      social, hereditary and genetic factors. The purpose of this study was to
      determine the associations between self-reported bruxism, anxiety, and
      neuroticism personality trait with the rs6313 polymorphism in the gene HTR2A. A
      sample of 171 subjects of both sexes (14-53 years of age) was included. The
      control group (group 1, n=60) exhibited no signs or symptoms of bruxism. The case
      group had signs and symptoms of bruxism (n=112) and was subdivided into group 2,
      bruxism during sleep (n=22); group 3, awake bruxism (n=44); and group 4 combined
      bruxism (n=46). As diagnostic tools, the Self-Reported Bruxism Questionnaire
      (SBQ), the Beck Anxiety Inventory (BAI) and the Eysenck Personality Questionnaire
      Revised-Abbreviated (EPQR-A) were used. HTR2A (rs6313) SNPs were determined by
      qPCR for all the participants. The packages SPSS, maxLik and EPI-INFO were used
      for data analysis. The combined bruxism group reported higher scores in bruxism
      symptoms, mean = 32.21; anxiety symptoms, mean = 14.80; and neuroticism, mean =
      3.26. Combined bruxism was associated with a higher degree of neuroticism
      (OR=15.0; CI 1.52-148.32) and anxiety in grade 3-moderate (OR=3.56; CI 1.27
      10.03), and grade 4-severe (OR=8.40; CI 1.45-48.61), as determined using EPISODE
      computer software. Genotypic homogeneity analysis revealed no significant
      differences in allele frequency (P=0.612) among the four groups. The population
      was in Hardy-Weinberg equilibrium (maxLik package). In conclusion, the three
      instruments confirm traits of bruxism, anxiety and neuroticism in individuals
      with bruxism. These data were ratified when the sample was divided by genotypic
      homogeneity. On the other hand, there was no significant difference between the
      groups in the SNPs rs6313 from the HTR2A gene.

PMID- 29599978
TI  - Association between heme oxygenase-1 gene promoter polymorphisms and cancer
      susceptibility: A meta-analysis.
AB  - Numerous studies have focused on the association between heme oxygenase-1 (HO-1)
      gene promoter polymorphisms and susceptibility to cancer; however, results remain
      ambiguous. The present systematic Human Genome Epidemiology review and meta
      analysis aimed to clarify this association. A systematic search was used to
      assess the association of HO-1 gene polymorphisms with cancer susceptibility in
      the PubMed, Web of Science, Cochrane Library, Wanfang Data and China National
      Knowledge Infrastructure databases, with all reviewed studies published before
      April 10, 2017. Review Manager 5.3 and Stata 12.0 software were used to perform
      the meta-analysis. A total of 14 studies were included in the analysis. Overall,
      no significant associations of the HO-1 (GT)n and T(-413)A polymorphisms with
      cancer susceptibility were identified. However, subgroup analyses by ethnicity
      and cancer type indicated that the LL and L-allele (LL+LS) genotypes of HO-1
      (GT)n were associated with increased susceptibility to cancer compared with the
      SS+SL and SS genotypes in the following subgroups: East Asian [LL+LS vs. SS: odds
      ratio (OR)=1.51, 95% confidence interval (CI)=1.11-2.05, P=0.0003; LL vs. SS+SL:
      OR=1.44, 95% CI=1.04-2.01, P=0.03; LL vs. SS: OR=1.64, 95% CI=1.07-2.52, P=0.02];
      squamous cell carcinoma (LL+LS vs. SS: OR=1.78, 95% CI=1.35-2.34, P<0.05; LL vs.
      SS+SL: OR=1.71, 95% CI=1.34-2.18, P<0.05; LL vs. SS: OR=2.26, 95% CI =1.62-3.14,
      P<0.05); and digestive tract cancer + East Asian (LL+LS vs. SS: OR=1.56, 95%
      CI=1.22-1.98, P<0.05; LL vs. SS: OR=1.80, 95% CI=1.06-3.05, P<0.05). These
      findings indicated that there was no association of the HO-1 (GT)n and T(-413)A
      polymorphisms with cancer susceptibility, while the L-allele genotypes (LL and
      LS) of HO-1 (GT)n may be susceptibility factors for cancer in East Asian,
      digestive tract cancer in East Asian and squamous cell carcinoma populations. Due
      to limitations of the reviewed studies, additional large-scale and refined
      studies are now required to confirm the present findings.

PMID- 29599980
TI  - Gender differences in the regulation of MLC20 phosphorylation and smooth muscle
      contraction in rat stomach.
AB  - Evidence of sex-related differences in gastrointestinal (GI) functions has been
      reported in the literature. In addition, various GI disorders have
      disproportionate prevalence between the sexes. An essential step in the
      initiation of smooth muscle contraction is the phosphorylation of the 20-kDa
      regulatory myosin light chain (MLC20) by the Ca2+/calmodulin-dependent myosin
      light chain kinase (MLCK). However, whether male stomach smooth muscle inherits
      different contractile signaling mechanisms for the regulation of MLC20
      phosphorylation from that in females has not been established. The present study
      was designed to investigate sex-associated differences in the regulation of MLC20
      phosphorylation and thus muscle contraction in gastric smooth muscle cells
      (GSMCs). Experiments were performed on GSMCs freshly isolated from male and
      female rats. Contraction of the GSMCs in response to acetylcholine (ACh), a
      muscarinic agonist, was measured via scanning micrometry in the presence or
      absence of the MLCK inhibitor, ML-7. Additionally, the protein levels of MLC20,
      MLCK and phosphorylated MLC20 were measured by ELISA. The protein levels of MLC20
      and MLCK were indifferent between the sexes. ACh induced greater contraction
      (P<0.05) as well as greater MLC20 phosphorylation (P<0.05) in male GSMCs compared
      with female. Pretreatment of GSMCs with ML-7 significantly reduced the ACh
      induced contraction (P<0.05) and MLC20 phosphorylation (P<0.05) in the male and
      female cells, and notably, abolished the contractile differences between the
      sexes. In conclusion, MLC20 phosphorylation and thus muscle contraction may be
      activated to a greater extent in male rat stomach compared with that in females.

PMID- 29599982
TI  - Solitary primary intracranial leptomeningeal glioblastoma invading the normal
      cortex: Case report.
AB  - Solitary primary intracranial leptomeningeal glioma (PLG) is a rare entity of
      glioma. PLG arises from the heterotopic glial tissue in the subarachnoid space
      and usually grows there without parenchymal invasion. The present study reported
      a case of solitary PLG, pathologically diagnosed as glioblastoma, that invaded
      the temporal cortex and finally disseminated to the spinal cord. A 55-year-old
      woman had headaches and visited Nihon University, Itabashi Hospital. Head
      magnetic resonance imaging showed a solid mass mainly located in the right middle
      fossa extending to the frontal base with strong enhancement effect after contrast
      medium injection. A conventional angiogram showed a tumor arising from the middle
      meningeal artery. Fronto-temporal craniotomy was performed to remove the tumor.
      During reflection of the dura matter, there were numerous small vessels
      connecting the dura matter and the cortical surface. The tumor was located in the
      Sylvian fissure and extended around the middle cerebral artery. The border
      between the tumor and the normal temporal lobe was unclear. Temporal lobectomy
      was done, but the tumor was left around the perforators of the middle cerebral
      artery. Hematoxylin and eosin staining showed typical glioblastoma with high
      cellularity, mitosis, pseudopallisading and vascular proliferation. The tumor
      cells were immunohistochemically negative for isocitrate dehydrogenase (IDH)1
      R132H indicating glioblastoma, IDH-wild type. The patient received chemotherapy
      and radiation therapy, and was discharged from the hospital. Six months later,
      local regrowth and spinal dissemination were found. Despite additional
      chemotherapy and radiation therapy, the tumor became uncontrollable and the
      patient succumbed. Only 15 cases of solitary PLGs have been reported previously.
      The IDH status of these tumors have not been investigated in most cases; however,
      pathological grading varies from lower to higher grade glioma. Together with the
      pathological difference of astrocytic or oligodendrocytic tumors, solitary PLGs
      may develop due to various gene alterations similar to intra-axial gliomas.

PMID- 29599981
TI  - Oxidative stress response induced by chemotherapy in leukemia treatment.
AB  - Oxidative stress (OS) has been linked to the etiology and development of leukemia
      as reactive oxygen species (ROS) and free radicals have been implicated in
      leukemogenesis. OS has beneficial and deleterious effects in the pathogenesis and
      progression of leukemia. High-dose chemotherapy, which is frequently used in
      leukemia treatment, is often accompanied by ROS-induced cytotoxicity. Thus, the
      utilization of chemotherapy in combination with antioxidants may attenuate
      leukemia progression, particularly for cases of refractory or relapsed neoplasms.
      The present review focuses on exploring the roles of OS in leukemogenesis and
      characterizing the associations between ROS and chemotherapy. Certain examples of
      treatment regimens wherein antioxidants are combined with chemotherapy are
      presented, in order to highlight the importance of antioxidant application in
      leukemia treatment, as well as the conflicting opinions regarding this method of
      therapy. Understanding the underlying mechanisms of OS generation will facilitate
      the elucidation of novel approaches to leukemia treatment.

PMID- 29599983
TI  - Patterning and fluorescence tuning of quantum dots with haptic-interfaced bubble
      printing.
AB  - Semiconductor quantum dots (QDs) are attractive for a wide range of applications
      such as displays, light-emitting devices, and sensors due to their properties
      such as tunable fluorescence wavelength, high brightness, and narrow bandwidth.
      Most of the applications require precise patterning of QDs with targeted
      properties on solid-state substrates. Herein, we have developed a haptic
      interfaced bubble printing (HIBP) technique to enable high-resolution (510 nm)
      high-throughput (>104 MUm s-1) patterning of QDs with strong emission tunability
      and to significantly enhance the accessibility of the technique via a smartphone
      device. The scalability and versatility of the HIBP are demonstrated in our
      arbitrary patterning of QDs on plasmonic substrates. A detailed study of
      plasmonic and photothermal interactions is performed via programmed stage
      movements to realize tunability of the emission wavelength and lifetime. Finally,
      the influence of the hand movement on the properties of the printed QDs in terms
      of emission wavelength tuning from yellow to blue is established. This work
      provides a single-step macroscale platform to manipulate nanoscale properties at
      high resolution and high throughput.

PMID- 29599985
TI  - Reluctant reviewers? Publons may help.

PMID- 29599984
TI  - A bibliometric analysis of the global research on biosimilars.
AB  - Background: Biosimilars could be a promising option to help decrease healthcare
      costs and expand access to treatment. There is no previous evidence of a global
      bibliometric analysis on biosimilars. Therefore, we aimed to assess the quantity
      and quality of worldwide biosimilars research. Methods: We performed a
      bibliometric analysis using documents about biosimilars published until December
      2016 in journals indexed in Scopus. We extracted the annual research, languages,
      countries, journals, authors, institutions, citation frequency, and the metrics
      of journals. The data were quantitatively and qualitatively analyzed using
      Microsoft Excel 2013. Additional information about authors' participation was
      obtained using the R-package Bibliometrix. Publication activity was adjusted for
      the countries by population size. Also, author co-citation analysis and a term co
      occurrence analysis with the terms included in the title and abstract of
      publications was presented as network visualization maps using VOSviewer.
      Results: A total of 2330 biosimilar-related documents identified in the Scopus
      database, most of them were articles (1452; 62.32%). The number of documents
      published had an exponential increased between 2004 and 2016 (p < 0.001). The
      United States was the country with the highest production with 685 (29.40%)
      documents followed by Germany and UK with 293 (12.58%) and 248 (10.64%),
      respectively. Switzerland (11.05), Netherlands (5.85) and UK (3.83) showed the
      highest per capita ratio. The highest citation/article ratio were for the
      Netherlands (28.06), Spain (24.23), and France (20.11). Gabi Journal published 73
      (3.13%) documents; both Biopharm International and Pharmaceutical Technology and
      Mabs, 41 (1.76%). Three out of top ten journals were Trade publications. Amgen
      Incorporated from the USA was the most prolific institution with 51 documents
      followed by Pfizer Inc. with 48. Terms about specific diseases and drugs were
      found in recent years, compared with terms such as legislation, structure,
      protein, dose and generic in the early years. Conclusions: Research production
      and publication of documents on biosimilars are increasing. The majority of
      publications came from high-income countries. The trends in terminology use are
      according to state of the art in the topic, and reflects the interest in the
      utilization of biosimilars in diseases who are expected to obtain benefits of its
      use.

PMID- 29599986
TI  - A discussion paper on stigmatizing features of diabetes.
AB  - Aim: This manuscript aims to describe stigmatizing features of diabetes. Design:
      This article presents a narrative review of literature pertaining to stigma
      surrounding diabetes in different contexts. Methods: A literature search was
      conducted in CINAHL, PubMed and Web of Science for qualitative studies published
      between 2007-2017. The search was completed using various combinations of
      diabetes, T1DM, T2DM, stigma, social/public stigma, internalized/self-stigma,
      stigmatization and diabetes-related stigma in English. The reviewers then
      independently reviewed the eligible studies (N = 18) to extract data. Results:
      From the 18 studies included in this narrative review, seven features related to
      stigma in diabetes were identified. People with diabetes were most notably
      considered and stigmatized as being "sick," "death reminder," "rejected marriage
      candidate," "self-inflicting," "contagiousness," "requiring a dietary
      modification" and "drunk or drug abuser."

PMID- 29599987
TI  - The care-planning conference: Exploring aspects of person-centred interactions.
AB  - Aim: The aim of this study was to describe the care-planning conference from the
      participants' and researchers' perspectives, focusing on exploring aspects of
      person-centred interactions. Design: A single-instrumental, qualitative case
      study design was used describing a care-planning conference taking place in the
      home of an older woman and her daughter. Methods: Data collection consisted of
      observation and digital recording of the care-planning conference and individual
      interviews with all the participants before and after the conference. Data were
      analysed in several phases: first, a narrative description followed by a general
      description and, thereafter, qualitative content analysis. Results: The findings
      revealed that the care-planning conference conducted had no clear purpose and did
      not fulfil all parts of the planning process. Three themes emerged related to
      aspects of person-centred interactions. The theme "expectations meet reality"
      showed different expectations, and participants could not really connect during
      the conference. The theme "navigate without a map" revealed health professionals'
      lack of knowledge about the care-planning process. The theme "lose the forest for
      the trees" described that the conference was conducted only as part of the health
      professionals' duties. Management and healthcare professionals cannot
      automatically assume that they are delivering person-centred care. Healthcare
      professionals need to be sensitive to the context, use the knowledge and tools
      available and continuously evaluate and reassess the work carried out.

PMID- 29599988
TI  - Contraceptives as possible risk factors for postpartum depression: A
      retrospective study of the food and drug administration adverse event reporting
      system, 2004-2015.
AB  - Aim: Postpartum depression is a mood disorder that commonly affects women during
      the early postpartum period. The objective of this study was to analyse the
      association of postpartum depression with drugs (including contraceptive devices
      and implants) with spontaneously reported adverse events reported in the US Food
      and Drug Administration Adverse Event Reporting System database. Design:
      Retrospective study. Method: Reports of postpartum depression events between 2004
      2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical
      Dictionary for Regulatory Activities was used to identify postpartum depression.
      Results: The reporting odds ratios (95% confidence intervals, CI) of
      levonorgestrel (an intrauterine device with progestogen), etonogestrel (a
      hormonal contraceptive implant), sertraline and drospirenone (an oral
      contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4
      (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration
      Adverse Event Reporting System database, the use of contraceptives or an
      intrauterine device with progestogen might convey risk for postpartum depression.

PMID- 29599989
TI  - What is desirable care in the opinion of formal and informal caregivers in
      nursing-home care for patients with dementia?
AB  - Aim: To examine care characteristics related to desirable care as reported by
      formal and informal caregivers in Dutch Psycho-geriatric nursing homes for
      patients with dementia. Design: Qualitative exploratory study. Methods: The
      sample consisted of four nursing homes. In each home, semi-structured interviews
      were conducted with a manager, a quality advisor or head nurse, a daily care
      supervisor and an informal caregiver. The findings were analysed by labelling and
      coding the text fragments. Results: The 16 semi-structured interviews contained
      60 discussion items. The 16 items that were shared by the four interviewee
      categories were clustered into the following six major themes: good quality of
      care; poor quality of care; elements of a vision; extra hands; bureaucracy; and
      formal caregivers.

PMID- 29599990
TI  - Patients' experiences of the transcatheter aortic valve implantation trajectory:
      A grounded theory study.
AB  - Aim: The aim of this study was to explore how patients experienced the recovery
      process from transcatheter aortic valve implantation. Design: A qualitative
      approach where in-depth interviews were used. Method: Eleven men and eight women
      undergoing transcatheter aortic valve implantation were individually interviewed
      6 months after transcatheter aortic valve implantation. Grounded theory was used
      for the analysis. Results: The analysis generated the core concept "A journey of
      balancing between life-struggle and hope" connected to descriptive, bipolar
      categories. Before transcatheter aortic valve implantation patients not only felt
      threatened but also experienced hope. The rehabilitation phase was described as
      demanding or surprisingly simple. At the 6 months follow-up patients were pleased
      to return to life, however, still struggling with limitations. To feel hope is
      essential for transcatheter aortic valve implantation patients' well-being, both
      before and during the recovery process. It is important that healthcare
      professionals not only support hopeful thinking but also take time to discuss and
      prepare patients, talk about concerns and build confidence. Individual plans for
      rehabilitation should be designed.

PMID- 29599991
TI  - Older people and their families' perceptions about their experiences with
      interprofessional teams.
AB  - Aim: To examine older people and their families' perceptions about their
      experiences with interprofessional teams. Design: Naturalistic inquiry using
      qualitative descriptive methods to provide a comprehensive summary of older
      people and their families' experiences with interprofessional teams. Methods:
      Interviews were conducted with 22 people from 11 families. The families had
      experiences with teams in a variety of settings, such as community, residential
      care and hospital. Data were analysed using inductive content analysis. NiVivo
      was used to record preliminary codes. Analysis included comparing and contrasting
      families' experiences. Results: Older people and their families wanted
      communication about what was going on, regardless of whether the news was good,
      bad or unknown. They also wanted care that took the concerns of the older person
      into consideration. Communication was a necessary ingredient to ensuring that the
      older person's unique concerns were known to the interprofessional team. These
      percepectives were discussed in the themes of communication and patient-centred
      care.

PMID- 29599992
TI  - Using a new interrater reliability method to test the modified Oulu Patient
      Classification instrument in home health care.
AB  - Aim: To test the interrater reliability of the modified Oulu Patient
      Classification instrument, using a multiple parallel classification method based
      on oral case presentations in home health care in Norway. Design: Reliability
      study. Methods: Data were collected at two municipal home healthcare units during
      2013-2014. The reliability of the modified OPCq instrument was tested using a new
      multiple parallel classification method. The data material consisted of 2 010
      parallel classifications, analysed using consensus in per cent and Cohen's kappa.
      Cronbach's alpha was used to measure internal consistency. Results: For parallel
      classifications, consensus varied between 64.78-77.61%. Interrater reliability
      varied between 0.49-0.69 (Cohen's kappa), the internal consistency between 0.81
      0.94 (Cronbach's alpha). Analysis of the raw scores showed 27.2% classifications
      had the same points, 39.1% differed one point, 17.9% differed two points and
      16.5% differed >=3 points.

PMID- 29599993
TI  - A mixed methods study of Tai Chi exercise for patients with chronic heart failure
      aged 70 years and older.
AB  - Aims and objectives: This study aimed to evaluate Tai Chi group training among
      patients with chronic heart failure (CHF) aged 70 years and older. Background:
      Physical activity is recommended for CHF treatment. Tai Chi is found to be
      beneficial to different patient groups, although few studies focus on older
      patients with CHF. Design: A mixed methods study. Participants were randomly
      assigned to Tai Chi training twice a week for 16 weeks (N = 25) or control (N =
      20). Quantitative data were collected at baseline, at the end of the training
      period and 6 months after training, assessing self-rated fatigue and quality of
      life, natriuretic peptides and physical performance. Individual qualitative
      interviews were conducted with participants (N = 10) in the Tai Chi training
      group. Results: No statistical differences between the Tai Chi training group and
      the control group in quality of life or natriuretic peptides was found. After 16
      weeks, the training group tended to rate more reduced activity and the control
      group rated more mental fatigue. Participants in the training group rated
      increased general fatigue at follow-up compared with baseline. Qualitative
      interviews showed that Tai Chi training was experienced as a new, feasible and
      meaningful activity. The importance of the leader and the group was emphasized.
      Improvements in balance were mentioned and there was no physical discomfort.
      Conclusion: Tai Chi was experienced as a feasible and meaningful form of physical
      exercise for patients with CHF aged over 70 years despite lack of achieved health
      improvement. Further investigations, using feasibility and meaningfulness as
      outcome variables seems to be useful.

PMID- 29599994
TI  - Course of maternal fatigue and its associated factors during the first 6 months
      postpartum: a prospective cohort study.
AB  - Aims: To identify the course of maternal fatigue during the first 6 months
      postpartum and to determine factors associated with it. Design: A prospective
      cohort study. Methods: Women (N = 2,697) in 13 Japanese hospitals provided
      longitudinal data using self-report questionnaires at five time points. Maternal
      fatigue was assessed using the Postnatal Accumulated Fatigue Scale. We focused on
      the effect of maternal age and parity on the course of maternal fatigue and used
      a mixed between/within-subjects analysis of variance. Factors associated with
      maternal fatigue were analysed using stepwise multiple regression. Results: In
      the 6-month postpartum period, the level of fatigue was highest at 1 month and
      significantly decreased from 1-4 months postpartum. Primiparas showed a
      significantly higher level of fatigue than multiparas during hospital stay and
      their levels of fatigue more closely approximated the 1-month peak. Multiparas
      showed significantly higher levels of fatigue than younger primiparas at 6-month
      postpartum. Factors associated with maternal fatigue included satisfaction with
      sleep, concerns about child-rearing, satisfaction with social support, financial
      burden and meal times per day.

PMID- 29599995
TI  - Surgery nurses' telephone communication: a mixed methods study with a special
      focus on newcomers' calls.
AB  - Aims: The aim of this study was (i) to document the main features of surgery
      nurses' telephone calls, with a special focus on newcomers' calls; and (ii) to
      identify the main activities accomplished during the newcomers' calls. Design:
      Mixed methods study. Methods: We audio recorded telephone calls internal to the
      hospital in two surgery nursing stations. We performed statistical descriptive
      analysis of the total collection of calls and of those specifically involving the
      newcomers and compared both sets. We also performed conversation analysis-based
      coding of the main activities accomplished during newcomers' calls. Results:
      Surgery nurses' telephone calls are extremely brief, predominantly nurse
      initiated and take place with a wide range of interlocutors who, for the most
      part, use mobile phones. The newcomers' calls are only slightly longer, take
      place with a more limited, but still wide, range of interlocutors and are even
      more often nurse initiated. The main activities of newcomers' calls are requests
      and activities related to connecting relevant interlocutors.

PMID- 29599996
TI  - Establishing a culturally specific nursing home for Finnish-speaking older
      persons in Sweden: A case study.
AB  - Aim: The study aims to describe the establishment of a culturally specific
      nursing home for Finnish-speaking older persons in Sweden. Design: A descriptive
      qualitative study. Methods: A descriptive case study based on a review of 14
      public documents and individual interviews with two experts in the area, analysed
      with qualitative content analysis. Results: This study found that shared
      language, preservation of customs and habits and collaboration between the
      representatives of the municipality, Finnish-speaking migrant associations and
      staff at the nursing home influenced the development of the culturally specific
      nursing home for older Finnish-speaking people intended to avoid loneliness,
      isolation and misunderstandings among older Finnish-speaking. Collaboration
      between healthcare service for older persons and minority people resulted in an
      optimal culturally specific nursing home, simultaneously encountering the
      majority culture. Nursing and healthcare services need to be aware of positive
      effects of collaboration with stakeholders to achieve optimal culturally specific
      nursing homes.

PMID- 29599997
TI  - First-line nurse managers' perceptions of the challenges involved in decision
      making when older patients' wish to die.
AB  - Aim: The aim of this study was to explore first-line nurse managers' perceptions
      of the challenges involved in decision-making concerning older patients who wish
      to die. Design: A descriptive qualitative design in three communities in Norway
      between January 2016 and June 2016. Methods: Qualitative focus group interviews
      with eight first-line nurse managers. Results: One main theme and two themes were
      identified: Struggling to make the right decision, The challenge of social
      isolation and loneliness and When life becomes too painful and problematic. The
      sub-themes revealed that: Arranging social meeting places where the older
      patients can talk to other older people is crucial. The participants explained
      that it was not an easy task to gain an overview of the older patients situation.
      The right decision could be encouraging the patients to talk about their problems
      by giving them more time, thereby showing that somebody cares about them.

PMID- 29599998
TI  - Patients' complaints regarding healthcare encounters and communication.
AB  - Aim: To explore patient-reported complaints regarding communication and
      healthcare encounters and how these were responded to by healthcare
      professionals. Design: A retrospective and descriptive design was used in a
      County Council in northern part of Sweden. Both quantitative and qualitative
      methods were used. Methods: The content of 587 patient-reported complaints was
      included in the study. Descriptive statistical analysis and a deductive content
      analysis were used to investigate the content in the patient-reported complaints.
      Results: The results show that patients' dissatisfaction with encounters and
      communication concerned all departments in the healthcare organization. Patients
      were most dissatisfied when they were not met in a professional manner. There
      were differences between genders, where women reported more complaints regarding
      their dissatisfaction with encounters and communication compared with men. Many
      of the answers on the patient-reported complaints lack a personal apology and
      some of the patients failed to receive an answer to their complaints.

PMID- 29599999
TI  - Innovation for the future of Irish MedTech industry: retrospective qualitative
      review of impact of BioInnovate Ireland's clinical fellows.
AB  - Clinicians have historically been integral in innovating and developing
      technology in medicine and surgery. In recent years, however, in an increasingly
      complex healthcare system, a doctor with innovative ideas is often left behind.
      Transition from idea to bedside now entails significant hurdles, which often go
      unrecognised at the outset, particularly for first-time innovators. The
      BioInnnovate Ireland process, based on the Stanford Biodesign Programme
      (Identify, Invent and Implement), aims to streamline the process of innovation
      within the MedTech sector. These programmes focus on needs-based innovation and
      enable multidisciplinary teams to innovate and collaborate more succinctly. In
      this preliminary study, the authors aimed to examine the impact of BioInnovate
      Ireland has had on the clinicians involved and validate the collaborative
      process. To date, 13 fellows with backgrounds in clinical medicine have
      participated in the BioInnovate programme. Ten of these clinicians remain
      involved in clinical innovation projects with four of these working on Enterprise
      Ireland funded commercialisation grants and one working as chief executive
      officer of a service-led start-up, Strive. Of these, five also remain engaged in
      clinical practice on a full or part-time basis. The clinicians who have returned
      to full-time clinical practice have used the process and learning of the
      programme to influence their individual clinical areas and actively seek
      innovative solutions to meet clinical challenges. Clinicians, in particular,
      describe gaining value from the BioInnovate programme in areas of 'Understanding
      Entrepreneurship' and 'Business Strategy'. Further study is needed into the
      quantitative impact on the ecosystem and impact to other stakeholders.

PMID- 29600000
TI  - Service user reflections on the impact of involvement in research.
AB  - Plain English summary: Public involvement can impact on research, on the public
      who give advice, on the researchers and the research participants. Evaluating
      impact is an important part of the research process. Two members of a hospital
      based patient research panel and our coordinator have written this paper. Our
      panel covers a range of rehabilitation and palliative services. These services
      form the "Therapeutics and Palliative Care Directorate". We describe how we
      worked collaboratively with hospital staff and co-produced questionnaires to
      evaluate the impact of our involvement. We compared the different perspectives of
      the researchers and panel members on our contribution to the research. We present
      evidence from these different standpoints, including how our panel made a
      difference. We found we needed to adapt how we collected the views of the
      researchers and our members to ensure it was meaningful to our group whilst
      delivering the wider objective of the hospital. A key finding has been how our
      involvement has extended into other groups, which has identified opportunities
      for sharing resources and experience, including areas such as cost effectiveness.
      Our two-person membership of a high level Board of Academics and Senior
      Clinicians, which oversees the research we contribute to, has resulted in our
      opinions influencing the heart of the Directorate's research strategy. We have
      learned the importance of a flexible approach as the Directorate changes, and the
      demands on us grow. This will continue to help us share our own development,
      successes and experience and extend the benefits from working this way. Abstract:
      Background Reports about the impact of patient and public involvement in research
      can be improved by involving patients and research staff more collaboratively to
      co-produce instruments to measure their involvement. This commentary, written by
      two members of a hospital-based patient panel and their coordinator for its work,
      describes how we co-produced instruments to evaluate the impact and effectiveness
      of our involvement. We present here the results, including our quantitative and
      qualitative findings, of this patient led evaluation and reflect on how our
      involvement has made a difference to the research projects and research
      infrastructure within the hospital in which we operate and on us as a panel.
      Methods Existing impact frameworks and guidelines were reviewed. Members co
      produced and piloted qualitative questionnaires to identify values associated
      with patient and public involvement (PPI) from both a researcher and panel member
      perspective, and collected quantitative metrics to provide descriptive statistics
      on the type of involvement and activities. Members also produced a comments slip
      to provide contemporaneous feedback after each meeting. Results The panel has
      reviewed 36 research projects for the Therapeutics and Palliative Care
      Directorate drawn from speech and language therapy, physiotherapy, occupational
      therapy, dietetics, podiatry, palliative care services and chaplaincy. Some of
      the main results of our involvement have been the development of grant
      applications and making written information more understandable for research
      participants. Examples of how the Panel made a difference included providing an
      effective forum for debate by providing practical suggestions to improve research
      design and identifying potential issues that may not have occurred to the
      researcher. The panel has had an impact outside of meetings both within the
      context in which it operates and on the individuals involved. Examples included:
      influencing the Directorate research agenda, sharing resources with other groups,
      developing research relationships, and enabling member participation in different
      roles and settings. Discussion Embedding ourselves within the Directorate
      research infrastructure has enabled us to adapt to organisational change and
      actively contribute to the research strategy. There is greater scope for
      involvement in areas of cost effectiveness and economic evaluation. Increasing
      member contributions and networking with other groups provides added value as
      well as cross fertilisation of ideas as part of our widening impact. Conclusion
      Evaluating the impact of our involvement has improved our understanding of what
      aspects of involvement work best for the panel and the researchers who attend our
      meetings, and in the different settings that we work in. It has helped us to
      focus on how we need to develop to maximise our resources going forward.

PMID- 29600001
TI  - BICAO-induced ischaemia caused depressive-like behaviours and caspase-8/-9
      dependent brain regional neural cell apoptosis in mice.
AB  - Introduction: Cerebral ischaemia-induced depression is among the most frequent
      neuropsychiatric consequences and adversely impact the prognosis and recovery of
      patients. Although several brain regions have been implied in the development of
      ischaemia-induced depression, the brain region-specific neural cell apoptosis
      pathways have not been clarified yet. Methods: In this study, bilateral internal
      carotid artery occlusion (BICAO) mouse model was established to induce cerebral
      ischaemia. Sucrose preference, tail suspension and forced swim tests were
      conducted on mice at 7, 21 and 30 days after BICAO treatment. In addition, brain
      regional ischaemic neuron loss was investigated by using immunofluorescent
      staining of neuronal nuclei (NeuN) and caspase-8/-9-dependent cell apoptosis was
      also examined by western blot analysis. Results: BICAO-induced cerebral ischaemia
      resulted in decreased sucrose preference and increased immobility times, which
      were representative depressive-like behaviours of mice until 30 days after BICAO
      treatment compared with Sham-operated mice. This outcome was associated with
      significant neuron loss by using immunofluorescent staining and increased
      cleavage levels of pro-caspase-3/-8/-9, but not pro-caspase-12, by western blot
      analysis in hypothalamus, midbrain, prefrontal cortex and hippocampus of mice.
      Conclusions: This study showed that BICAO-induced ischaemia caused depressive
      like behaviours and caspase-8/-9-dependent neural cell apoptosis in several brain
      regions, including hypothalamus and midbrain of mice.

PMID- 29600002
TI  - Prestroke selective serotonin reuptake inhibitor use and functional outcomes
      after ischaemic stroke.
AB  - Background: Selective serotonin reuptake inhibitors (SSRIs) have been implicated
      in contributing to recovery after acute ischaemic stroke. In particular,
      poststroke initiation of an SSRI has been demonstrated to improve motor recovery.
      The role of prestroke SSRI use on functional outcomes and stroke recovery is less
      clear. We aimed to examine the effect of prestroke SSRI use on metrics of
      hospitalisation and functional recovery. Methods: We included 4968 consecutive
      patients from January 2006 to June 2015 in our local Get With The Guidelines
      Stroke registry in whom a preadmission drug list could be extracted from an
      administrative research data registry. Univariate and multivariate analyses were
      performed to identify predictors of functional outcomes. Results: On univariate
      analysis, among 4698 ischaemic strokes (740 SSRI users and 3948 non-users), SSRI
      use before acute ischaemic stroke did not impact the National Institutes of
      Health Stroke Scale (NIHSS) admission score, length of stay or rate of
      symptomatic haemorrhage. Patients using SSRIs prior to their stroke were more
      likely to present with weakness (57% vs 47.3%; P<0.001) and have hospitalisations
      complicated by pneumonia (7.6% vs 5.7%; P<0.001). Moreover, prestroke SSRI use
      was associated with a negative impact on ambulatory status at discharge and
      discharge to home. On multivariate regression analysis, SSRI use was associated
      with lower likelihood of discharge to home (adjusted OR 0.79, 95% CI 0.62 to
      0.997, P<0.05). Conclusions: SSRI use preceding an acute ischaemic stroke is
      associated with lower rates of discharge to home despite no significant increase
      in length of stay or NIHSS score.

PMID- 29600003
TI  - Endovascular revascularisation of acute tandem vertebrobasilar artery occlusion:
      seven case series with literature reviews.
AB  - Background: The outcome of acute ischaemic stroke due to tandem vertebrobasilar
      artery occlusion was poor. Endovascular revascularisation may be a positive
      approach for acute basilar artery occlusion combined with vertebral ostium
      stenosis or occlusion. We reported seven patients with acute vertebrobasilar
      tandem occlusion by using angioplasty or stenting for proximal lesion and
      thrombectomy for distal occlusion. Materials and methods: Consecutive patients
      with acute tandem vertebrobasilar artery occlusion at two centres were included
      in this study. We retrospectively analysed the clinical, technical and functional
      outcomes of the patients. Results: From March 2016 to March 2017, seven patients
      were included. The mean age and National Institute of Health Stroke Scale score
      at admission was 57 years and 22, respectively. A reverse approach was used in
      five patients. The Thrombolysis in Cerebral Infarction score 2b-3 was acquired in
      all patients. There were no procedural complications. The modified Rankin Scale
      score was 1-2 for three patients and 4 for one patient at 3 months. Three
      patients died at 3 months of follow-up. Conclusions: Endovascular
      revascularisation may be feasible for acute tandem vertebrobasilar artery
      occlusion, and more researches are needed.

PMID- 29600004
TI  - Efficacy and safety of intravenous recombinant tissue plasminogen activator in
      mild ischaemic stroke: a meta-analysis.
AB  - The benefits and safety of intravenous recombinant tissue plasminogen activator
      (IV-tPA) for patients with mild ischaemic stroke (MIS) are still unclear. The
      objective of this meta-analysis was to evaluate the efficacy and safety of IV-tPA
      as treatment for patients with MIS. We performed a systematic literature search
      across MEDLINE, Embase, Central, Global Health and Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), from inception to 10 November 2016, to
      identify all related studies. Where possible, data were pooled for meta-analysis
      with odds ratio (OR) and corresponding 95% confidence interval (CI) using the
      fixed-effects model. MIS was defined as having National Institutes of Health
      Stroke Scale score of <=6. We included seven studies with a total of 1591
      patients based on the prespecified inclusion and exclusion criteria. The meta
      analysis indicated a high odds of excellent functional outcome based on the
      modified Rankin Scale or Oxfordshire Handicap Score 0-1 (OR=1.43; 95% CI 1.14 to
      1.79; P=0.002, I2=35%) in patients treated with IV-tPA compared with those not
      treated with IV-tPA (74.8% vs 67.6%). There was a high risk of symptomatic
      intracranial haemorrhage (sICH) with IV-tPA treatment (OR=10.13; 95% CI 1.93 to
      53.02; P=0.006, I2=0%) (1.9% vs 0.0%) but not mortality (OR=0.78; 95% CI 0.43 to
      1.43; P=0.43, I2=0%) (2.4% vs 2.9%). Treatment with IV-tPA was associated with
      better functional outcome but not mortality among patients with MIS, although
      there was an increased risk of sICH. Randomised trials are warranted to confirm
      these findings.

PMID- 29600005
TI  - Current status of intravenous tissue plasminogen activator dosage for acute
      ischaemic stroke: an updated systematic review.
AB  - The optimal dose of recombinant tissue plasminogen activator (rtPA) for acute
      ischaemic stroke (AIS) remains controversial, especially in Asian countries. We
      aimed to update the evidence regarding the use of low-dose versus standard-dose
      rtPA. We performed a systematic literature search across MEDLINE, Embase,
      Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO and Cumulative
      Index to Nursing and Allied Health Literature (CINAHL) from inception to 22
      August 2016 to identify all related studies. The outcomes were death or
      disability (defined by modified Rankin Scale 2-6), death, and symptomatic
      intracerebral haemorrhage (sICH). Where possible, data were pooled for meta
      analysis with ORs and corresponding 95% CIs by means of random-effects or fixed
      effects meta-analysis. We included 26 observational studies and 1 randomised
      controlled trial with a total of 23 210 patients. Variable doses of rtPA were
      used for thrombolysis of AIS in Asia. Meta-analysis shows that low-dose rtPA was
      not associated with increased risk of death or disability (OR 1.13, 95% CI 0.95
      to 1.33), or death (OR 0.86, 95% CI 0.74 to 1.01), or decreased risk of sICH (OR
      1.06, 95% CI 0.65 to 1.72). The results remained consistent when sensitivity
      analyses were performed including only low-dose and standard-dose rtPA or only
      Asian studies. Our review shows small difference between the outcomes or the risk
      profile in the studies using low-dose and/or standard-dose rtPA for AIS. Low-dose
      rtPA was not associated with lower risk of death or disability, death alone, or
      sICH.

PMID- 29600007
TI  - Not so FAST-let's not abandon the pediatric focused assessment with sonography in
      trauma yet.

PMID- 29600006
TI  - Stroke-induced immunosuppression and poststroke infection.
AB  - Infections occur commonly after stroke and are strongly associated with an
      unfavourable functional outcome of these patients. Approaches for effective
      management of poststroke infection remain scarce, presenting an urgent need for
      preventive anti-infection strategies for patients who have suffered a stroke.
      Emerging evidence indicates that stroke impairs systemic immune responses and
      increases the susceptibility to infections, suggesting that the modification of
      impaired immune defence could be beneficial. In this review, we summarised
      previous attempts to prevent poststroke infections using prophylactic antibiotics
      and the current understanding of stroke-induced immunosuppression. Further
      elucidation of the immune mechanisms of stroke will pave the way to tailored
      design of new treatment to combat poststroke infection via modifying the immune
      system.

PMID- 29600008
TI  - Lung cancer recurrence epigenetic liquid biopsy.

PMID- 29600009
TI  - Editorial for economic impact of an enhanced recovery pathway for lung resection.

PMID- 29600010
TI  - Temperature and duration targets during post-arrest care: choosing the right
      prescription for the right patient.

PMID- 29600011
TI  - Lymph node assessment and survival: we still have work to do.

PMID- 29600012
TI  - Prime time for the sweet spot in timing of coronary invasive approach in patients
      with non-ST elevation myocardial infarction.

PMID- 29600013
TI  - Stereotactic ablative radiotherapy for oligometastatic non-small cell lung
      cancer.

PMID- 29600014
TI  - Square peg, round hole? Programmed death-1 inhibitors in epidermal growth factor
      receptor-mutant non-small cell lung cancer.

PMID- 29600015
TI  - Heart-breaking aspirin interruption.

PMID- 29600016
TI  - Why did VALIDATE-SWEDEHEART not validate the results of HORIZONS?

PMID- 29600017
TI  - Lobar or sublobar resection for stage I lung cancer: that is (still) the
      question!

PMID- 29600018
TI  - Obstructive sleep apnea and chronic kidney disease: open questions on a potential
      public health problem.

PMID- 29600019
TI  - Targeted temperature management after cardiac arrest: the longer, the better?

PMID- 29600020
TI  - Personalized surgery for the management of pulmonary metastasis.

PMID- 29600021
TI  - Higher vs. lower PEEP in ARDS: just one part of the whole.

PMID- 29600022
TI  - Expanding role for radiotherapy in metastatic non-small cell lung cancer in the
      era of targeted therapy and immuno-oncology.

PMID- 29600023
TI  - The quest for immunotherapy in atherosclerosis: CANTOS study, interleukin-1beta
      and vascular inflammation.

PMID- 29600024
TI  - Does VALIDATE-SWEDEHEART invalidate the use of bivalirudin in myocardial
      infarction?

PMID- 29600025
TI  - Cardiovascular events after discontinuation of low-dose aspirin.

PMID- 29600026
TI  - The significance of pathological extracapsular vs. intracapsular lymph node
      involvement in patients with resectable esophageal cancer after neoadjuvant
      therapy.

PMID- 29600027
TI  - New individualized strategy instructs cryoballoon energy ablation.

PMID- 29600028
TI  - Is there still a role for alveolar recruitment maneuvers in acute respiratory
      distress syndrome?

PMID- 29600029
TI  - Lung protection in patients undergoing pulmonary lobectomy: a new perspective for
      remote ischemic conditioning in surgery?

PMID- 29600030
TI  - A perspective on the Society of Thoracic Surgeons Composite Score for evaluating
      esophagectomy for esophageal cancer.

PMID- 29600031
TI  - Remote ischaemic preconditioning of the lung: from bench to bedside-are we there
      yet?

PMID- 29600032
TI  - The enigma of the weekend effect.

PMID- 29600033
TI  - J-ALEX trial will crown alectinib as the standard choice for anaplastic lymphoma
      kinase positive untreated non-small cell lung cancer patients?

PMID- 29600034
TI  - Examining the paradox of high high-density lipoprotein and elevated
      cardiovascular risk.

PMID- 29600035
TI  - Perspectives on oligometastasis: challenges and opportunities.

PMID- 29600036
TI  - Ridinilazole-a novel antibiotic for treatment of Clostridium difficile infection.

PMID- 29600037
TI  - Editorial on "Growth patterns of pulmonary metastases: should we adjust resection
      techniques to primary histology and size?"

PMID- 29600038
TI  - The role of loop gain in predicting upper airway surgical outcomes-what do we
      know?

PMID- 29600039
TI  - Breaking the dose ceiling: proton therapy for locally advanced non-small cell
      lung cancer.

PMID- 29600040
TI  - The 25th birthday and premature death of the open lung approach?-from science,
      through art, towards precision medicine.

PMID- 29600041
TI  - Ablative therapy in oligometastatic non-small cell lung cancer-an editorial on
      recent evidence.

PMID- 29600042
TI  - Malapposed, uncovered, underexpanded-intravascular imaging lessons on coronary
      stent thrombosis.

PMID- 29600043
TI  - Non-intubated uniportal video-assisted thoracoscopic surgery for carinal sleeve
      resection-is surgical process almost completed?

PMID- 29600044
TI  - Identification of the key transcription factors in esophageal squamous cell
      carcinoma.
AB  - Background: Esophageal cancer (EC) is a common human malignancy worldwide.
      Esophageal squamous cell carcinoma (ESCC) is the predominant subtype in China.
      The tumorigenesis mechanism in ESCC is unclear. The aim of this study was to
      identify key transcription factors (TFs) in ESCC and elucidate the mechanism of
      it. Methods: A total of ten published microarray datasets of ESCC was downloaded
      from the Gene Expression Omnibus (GEO). Then, bioinformatics analyses including
      differentially expressed genes (DEGs) analysis, gene ontology (GO) annotation,
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, TFs-genes
      regulatory network construction was performed. Quantitative real-time polymerase
      chain reactions (qRT-PCR) were used to detect the expression levels of TFs and
      DEGs in ESCC. The association between stage and TFs and the association between
      survival and TFs were evaluated based on The Cancer Genome Atlas (TCGA),
      respectively. Results: A total of 1,248 dysregulated genes were selected as DEGs
      in ESCC. A total of 26 TFs and corresponding target-genes were identified. The
      ESCC-specific transcriptional regulatory network was constructed. The network was
      consisted of 882 edges and 631 nodes. BRCA1, SOX10, ARID3A, ZNF354C and NFIC had
      the highest connectivity with DEGs, and regulated 92, 89, 82, 79 and 78 DEGs in
      the network, respectively. All these 1,248 DEGs were significantly enriched in
      cell cycle, DNA replication and oocyte meiosis pathways. The qRT-PCR results were
      consistent with our microarray analysis. High expression of SREBF1 and TFAP2A
      were significantly correlated with the longer overall survival time of patients
      with ESCC. Conclusions: BRCA1, SOX10, ARID3A, ZNF354C and NFIC might be the key
      TFs in carcinogenesis and development of ESCC by regulating their corresponding
      target-genes involved in cell cycle, DNA replication and oocyte meiosis pathways.
      SREBF1 and TFAP2A may be two potential prognostic biomarkers of ESCC.

PMID- 29600045
TI  - Validation of the T descriptor in the new 8th TNM classification for non-small
      cell lung cancer.
AB  - Background: To validate new proposals for the revision of T descriptors and to
      compare the prognostic value of the seventh and forthcoming eighth edition of the
      tumor, node and metastasis (TNM) classification for lung cancer. Methods: A
      retrospective analysis was conducted of 1,316 patients with non-small lung cancer
      who underwent pulmonary resection between 1999 and 2012. Patients who had a
      positive nodal status or distant metastasis were excluded. We classified these
      patients according to the seventh and eighth edition of the TNM system, and
      analyzed differences in stage specific survival. Harrell's concordance (C)-index
      and Heagerty's integrated area under the curve (iAUC) were used to assess the
      overall predictive ability of the different TNM versions. Results: There were no
      significant survival differences between each stage based on the T stage criteria
      of the eighth edition, most notably between T1a and T1b (P=0.752), and T1c, T2a,
      and T2b (P=0.832). The C-indices of the classification based on the seventh and
      eighth edition were 0.681 and 0.675, respectively. There was no significant
      difference in the C-indices between the seventh and eighth edition. The iAUC
      value for overall survival of the seventh and eighth staging editions was 0.637
      and 0.631, respectively. The differences in iAUC between the seventh and eighth
      editions were also not statistically significant. Conclusions: The newly proposed
      T descriptors in the eighth TNM classification system did not allow a more
      accurate prediction of prognosis compared with the current seventh edition in our
      population.

PMID- 29600046
TI  - Bronchoalveolar lavage fluid microbiota dysbiosis in infants with protracted
      bacterial bronchitis.
AB  - Background: Protracted bacterial bronchitis (PBB) is a chronic purulent
      bronchitis which could cause recurrent coughing and wheezing in infants. Based on
      previous reports, main pathogens which caused PBB were identified in the
      patients, but their impacts on lung microbiota dysbiosis remain unclear. Methods:
      In this study, bronchoalveolar lavage fluid (BALF) was collected from PBB infants
      and tracheomalacia (TM) infants younger than 3 years old under the instruction of
      Shenzhen Children's Hospital, and 12 samples were randomly selected for 16S rDNA
      analysis in each group. Based on the results of bacterial composition, the
      microbiota diversity and co-occurrence network in PBB and TM group were detected
      and compared. Results: Microbiota diversity was significantly lower in PBB group
      than it in TM group (P<0.001 for the comparison of Shannon and Simpson indexes).
      The PBB group was found to harbor 25 accumulated bacterial agents by comparison
      with TM group, including Haemophilus (P<0.001) and Bacteroides (P<0.001). Whilst,
      the populations of Lactococcus (P<0.001) and Lactobacillus (P<0.001) were
      dramatically smaller in PBB group. The co-occurrence network in PBB group also
      differed from that of TM group. It contained four core nodes in PBB patients,
      including Haemophilus, Parabacteroides, Porphyromonas, and Cronobacter.
      Haemophilus was found to be negatively associated with most counterparts,
      including Clostridium and Bacillus. Conclusions: PBB infants contained discrepant
      lung genera and co-occurrence network when compared with TM infants. This
      retrospective study may deepen our understanding of PBB pathogenesis, and it also
      provided a foundation for bacterial adjunctive therapy of infantile PBB in
      accordance with clinical treatment.

PMID- 29600047
TI  - Evaluation of the 95% limits of agreement of the volumes of 5-year clinically
      stable solid nodules for the development of a follow-up system for indeterminate
      solid nodules in CT lung cancer screening.
AB  - Background: This study sought to evaluate the 95% limits of agreement of the
      volumes of 5-year clinically stable solid nodules for the development of a follow
      up system for indeterminate solid nodules. Methods: The volumes of 226 solid
      nodules that had been clinically stable for 5 years were measured in 186 patients
      (53 female never-smokers, 36 male never-smokers, 51 males with <30 pack-years,
      and 46 males with >=30 pack-years) using a three-dimensional semiautomated
      method. Volume changes were evaluated using three methods: percent change,
      proportional change and growth rate. The 95% limits of agreement were evaluated
      using the Bland-Altman method. Results: The 95% limits of agreement were as
      follows: range of percent change, from +/-34.5% to +/-37.8%; range of
      proportional change, from +/-34.1% to +/-36.8%; and range of growth rate, from +/
      39.2% to +/-47.4%. Percent change-based, proportional change-based, and growth
      rate-based diagnoses of an increase or decrease in ten solid nodules were made at
      a mean of 302+/-402, 367+/-455, and 329+/-496 days, respectively, compared with a
      clinical diagnosis made at 809+/-616 days (P<0.05). Conclusions: The 95% limits
      of agreement for volume change in 5-year stable solid nodules may enable the
      detection of an increase or decrease in the solid nodule at an earlier stage than
      that enabled by a clinical diagnosis, possibly contributing to the development of
      a follow-up system for reducing the number of additional Computed tomography (CT)
      scans performed during the follow-up period.

PMID- 29600048
TI  - Correlation of bispectral index and Richmond agitation sedation scale for
      evaluating sedation depth: a retrospective study.
AB  - Background: This study aims to verify the correlation of bispectral index (BIS)
      and Richmond agitation sedation scale (RASS) for evaluating these and explore
      possibility of replacing RASS with BIS. Methods: This retrospective cohort study
      consisted of 74 patients who were collected from the third Intensive Care Unit
      (ICU) ward of XXX Hospital between May 2012 and June 2015 in this retrospective
      study. Sedation levels were evaluated using the 10-grade RASS and were
      continuously monitored with a BIS monitor during the procedure every 5 minutes.
      BIS values and RASS scores were recorded. Results: Patients were divided into
      dexmedetomidine (n=31) and midazolam (n=43) groups, and 342 paired data were
      collected. A statistically significant correlation existed between BIS values and
      RASS scores either in all patients undergoing flexible fiberoptic bronchoscopy
      (FFB) or in dexmedetomidine and midazolam groups at different time points.
      Correlation coefficient was higher in midazolam group compared with
      dexmedetomidine group at different time points (P<0.05). Conclusions: A
      correlation was observed between BIS and RASS for evaluating depth of sedation in
      ICU patients undergoing FFB (P<0.05). Study results indicated that BIS monitoring
      is a meaningful tool, which can be applied as an adjunctive and alternative
      method to assess sedation, especially for high-risk patients who are prone to be
      under- or over-sedation.

PMID- 29600049
TI  - Three-dimensional computed tomography reconstruction for operative planning in
      robotic segmentectomy: a pilot study.
AB  - Background: The objective of our pilot study was to assess if three-dimensional
      (3D) reconstruction performed by Visible PatientTM could be helpful for the
      operative planning, efficiency and safety of robot-assisted segmentectomy.
      Methods: Between 2014 and 2015, 3D reconstructions were provided by the Visible
      PatientTM online service and used for the operative planning of robotic
      segmentectomy. To obtain 3D reconstruction, the surgeon uploaded the anonymized
      computed tomography (CT) image of the patient to the secured Visible PatientTM
      server and then downloaded the model after completion. Results: Nine
      segmentectomies were performed between 2014 and 2015 using a pre-operative 3D
      model. All 3D reconstructions met our expectations: anatomical accuracy (bronchi,
      arteries, veins, tumor, and the thoracic wall with intercostal spaces), accurate
      delimitation of each segment in the lobe of interest, margin resection, free
      space rotation, portability (smartphone, tablet) and time saving technique.
      Conclusions: We have shown that operative planning by 3D CT using Visible
      PatientTM reconstruction is useful in our practice of robot-assisted
      segmentectomy. The main disadvantage is the high cost. Its impact on reducing
      complications and improving surgical efficiency is the object of an ongoing
      study.

PMID- 29600050
TI  - PTEN gene silencing contributes to airway remodeling and induces airway smooth
      muscle cell proliferation in mice with allergic asthma.
AB  - Background: Allergic asthma is a complex genetic disorder that involves
      interactions between genetic and environmental factors. Usage of PTEN may be a
      good therapeutic strategy for the management of allergic inflammation. Thus, the
      present study aims to explore the effects of phosphatase and tensin homolog
      (PTEN) gene silencing on airway remodeling and proliferation of airway smooth
      muscle cells (ASMCs) in a mouse model of allergic asthma. Methods: A total of 56
      healthy female BABL/c mice (weighing between 16 to 22 grams) were selected and
      were assigned on random into ovalbumin (OVA; mice were stimulated with OVA to
      induce allergic asthma), OVA + si-PTEN, normal saline (NS; mice were treated with
      normal saline) and NS + si-PTEN groups. Masson staining was employed in order to
      observe lung tissue sections. Immunohistochemical staining was used to detect the
      expression of alpha-SMA+. Gene silencing was conducted in the NS + si-PTEN and
      OVA + si-PTEN groups. Quantitative reverse transcription polymerase chain
      reaction (qRT-PCR) and western blotting were used to detect the mRNA and protein
      expressions of PTEN in ASMCs of each group. CCK-8 assay and flow cytometry were
      performed to determine the cell proliferation rate and cell cycle. Results:
      Airway remodeling and changes of smooth muscle layer were found in allergic
      asthmatic mice with thick airway walls. The expression of alpha smooth muscle
      actin (alpha-SMA+) was significantly higher in ASMCs of the OVA, OVA + si-PTEN
      and NS + si-PTEN groups compared with ASMCs of the NS group. The mRNA and protein
      expressions of PTEN reduced in the OVA, OVA + si-PTEN and NS + si-PTEN groups.
      The rate of ASMCs proliferation in OVA, OVA + si-PTEN and NS + si-PTEN groups
      were significantly higher than the NS group. The proportion of ASMCs in S and G2
      stages increased, while the number of cells in the G1 stage decreased after PTEN
      gene silencing. Conclusions: These results demonstrated that PTEN gene silencing
      might promote proliferation of ASMCs and airway remodeling in a mouse model of
      allergic asthma.

PMID- 29600051
TI  - In vitro effects of N-acetylcysteine alone and combined with tigecycline on
      planktonic cells and biofilms of Acinetobacter baumannii.
AB  - Background: Acinetobacter baumannii (A. baumannii), as a common opportunistic
      pathogen, has strong ability to form biofilms, which has led to drug resistance
      and chronic infections. The combination of N-acetylcysteine (NAC) and tigecycline
      (TGC) was demonstrated to synergistically inhibit biofilm-associated bacterial
      infections, including methicillin-resistant Staphylococcus aureus and
      Staphylococcus epidermidis. The purpose of this study is to investigate the
      effect of NAC and TGC on planktonic cells and biofilms of A. baumannii. Methods:
      Minimum inhibitory concentrations (MICs) of NAC were determined by broth
      microdilution method. Biofilm susceptibility was assessed by crystal violet
      stain. Interactive effects of NAC and TGC on planktonic cells were determined by
      checkerboard MIC assay. Viable cell count was used to evaluate the combined
      effect of NAC and TGC on biofilm-embedded bacteria. Results: MICs of NAC against
      25 A. baumannii isolates ranged from 16 to 128 mg/mL. NAC alone (0.5-128 mg/mL)
      significantly inhibited biofilm formation and disrupted preformed biofilms. The
      combination of NAC and TGC induced a partial synergistic effect (60%) and
      additive effect (28%) on planktonic bacteria. For biofilm-embedded bacteria,
      treatment with 16 mg/mL NAC alone or 2 ug/mL TGC alone resulted in significant
      bactericidal effects (P<0.01 and P<0.05, respectively); synergistic bactericidal
      effect was found at 4 mg/mL NAC combined with 0.5 ug/mL TGC (P<0.01).
      Conclusions: NAC alone significantly inhibited biofilm formation of A. baumannii.
      The combination of NAC and TGC induced partial synergistic effect against
      planktonic cells and synergistic effect against biofilm-embedded A. baumannii,
      which might be a therapeutic option for biofilm-related infections of A.
      baumannii.

PMID- 29600052
TI  - A pooled analysis of advanced nonsquamous non-small cell lung cancer patients
      with stable treated brain metastases in two phase II trials receiving bevacizumab
      and pemetrexed as second-line therapy.
AB  - Background: Brain metastases are a common complication of advanced non-small cell
      lung cancer (NSCLC). Patients with brain metastases were excluded from the
      registration trials of bevacizumab that showed a survival benefit with the use of
      angiogenesis inhibition. Methods: In this study, we pooled data from two separate
      trials designed to evaluate the risk of central nervous system (CNS) hemorrhage
      in patients with stable treated brain metastases to look specifically at both the
      safety and efficacy of bevacizumab and pemetrexed when used as second-line
      treatment in NSCLC patients with stable treated brain metastases. Results: We
      report acceptable safety and promising efficacy from our analysis. Conclusions:
      Our study adds further evidence of safety of administering pemetrexed and
      bevacizumab to patients with stable brain metastases. There is increasing roles
      for systemic therapies to treat stable brain metastases for patients with
      advanced NSCLC.

PMID- 29600053
TI  - Long-term quality of life after endovac-therapy in anastomotic leakages after
      esophagectomy.
AB  - Background: Endoluminal vacuum therapy (EVT) has been successfully established
      with promising survival rates in the treatment of anastomotic leakages after
      esophagectomy. It is still unclear how this therapy affects health related
      quality of life (HRQOL). Methods: HRQOL was prospectively assessed using the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire-C30 (EORTC QLQ-C30) questionnaire. Assessment was carried out prior
      to surgery, after discharge, 6 months and 12 months after surgery. We compared
      HRQOL after EVT (n=23) to patients without anastomotic leakages as a control
      group (n=50). Investigated parameters included age, sex, and localization of
      anastomosis, number of EVT sessions, length of ICU and hospital stay, therapy
      failure, anastomotic stricture, tumour stage, neoadjuvant and adjuvant treatment,
      sepsis. Results: After esophagectomy HRQOL increased within 12 months. Compared
      to patients without leakages the EVT-group showed significantly better HRQOL
      scores for pain, social and emotional functioning after discharge and 6 months
      after surgery. In the long-term follow up HRQOL was comparable between the
      groups. After EVT age, advanced tumour stage, tumour recurrence, anastomotic
      strictures, length of ICU and hospital stay and length of EVT had a significant
      influence on HRQOL. Conclusions: EVT is a promising therapeutic option in
      leakages after esophagectomy. In the long-term, HRQOL of EVT-treated patients is
      comparable to patients, who did not suffer from postsurgical leakages.

PMID- 29600054
TI  - Manual aspiration in the biopsy-side down position to deal with delayed
      pneumothorax after lung biopsy.
AB  - Background: To assess the effect of aspiration in the biopsy-side down position
      to deal with delayed pneumothorax after computed tomography (CT)-guided lung
      biopsy. Methods: A retrospective review was performed of the 236 delayed
      pneumothorax patients who underwent CT-guided transthoracic needle biopsies
      (TTNBs). Asymptomatic minimal pneumothorax patients were managed conservatively.
      Manual aspirations were applied for symptomatic cases with minimal pneumothorax
      and all cases with moderate to large pneumothorax. Patients were included into
      two groups: in group A (35 patients), aspiration was performed in the same
      position as the biopsy, while in group B (54 patients), patients were turned to
      the biopsy-side down position (from supine to prone or vice versa), and
      aspiration was conducted. The efficacy of two approaches was evaluated. Results:
      One hundred forty-seven (62.3%) asymptomatic cases resolved without treatment.
      Distance between parietal and visceral pleura before and after aspiration were
      4.24+/-1.87 and 1.93+/-2.33 cm for group A, 3.92+/-1.31 and 0.98+/-1.50 cm for
      group B, respectively. Volume of aspirated air in group A and group B were
      735.4+/-231.8 and 434.8+/-320.3 mL, respectively. Complete lung expansion was
      detected in 28.6% (10/35) and 38.9% (21/54) for group A and group B,
      respectively. The overall effective rate and failure rate were 74.3% (26/35) and
      25.7%(9/35) for group A, 92.6% (50/54) and 7.4%((4/54))for group B, respectively,
      which have significant statistic difference (P<0.05). Conclusions: Manual
      aspiration in biopsy-side down position demonstrates the safety and efficacy in
      treating delayed pneumothorax after CT-guided TTNBs. Thus reduce the rate of
      pneumothorax requiring drainage catheter placement.

PMID- 29600055
TI  - Clarithromycin mitigates radiation pneumonitis in patients with lung cancer
      treated with stereotactic body radiotherapy.
AB  - Background: Radiation pneumonitis is a critical pulmonary toxicity after
      irradiation of the lung. Macrolides including clarithromycin (CAM) are
      antibiotics. They also have immunomodulatory properties and are used to treat
      respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to
      them. Adverse reactions to macrolides are few and self-limited. We thus
      administered CAM to patients with high-risk factors for radiation pneumonitis,
      and retrospectively investigated whether CAM mitigated radiation pneumonitis
      following stereotactic body radiotherapy (SBRT). Methods: Among consecutive
      patients treated with SBRT, we retrospectively examined lung cancer patients
      treated with a total dose of 40-60 Gy in 5-10 fractions and followed >=6 months.
      Since January 2014, CAM has been administered in patients with pretreatment
      predictable radiation pneumonitis high-risk factors, including idiopathic
      interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or
      surfactant protein D (SP-D), and in patients developing early onset radiation
      pneumonitis. Results: Five hundred and eighty eligible patients were identified
      and divided into 445 patients during the non-CAM-administration era (non-CAM-era)
      (before December 2013) and 136 patients during the CAM-administration era (CAM
      era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months,
      respectively. The rates of radiation pneumonitis >= grade 2 and >= grade 3 were
      significantly lower in CAM-era (grade >=2, 16% vs. 9.6%, P=0.047; grade >=3, 3.8%
      vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk
      factors, the rate of radiation pneumonitis >= grade 3 was significantly lower,
      and that of grade >=2 had a lower tendency (grade >=3, 7.2% vs. 0%, P=0.011;
      grade >=2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation
      pneumonitis, the rate of radiation pneumonitis >= grade 3 was also significantly
      lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric
      factor, the pretreatment predictable high-risk factors and non-CAM-administration
      era were significantly associated with or trended toward radiation pneumonitis >=
      grade 2 and >= grade 3. Conclusions: CAM mitigated radiation pneumonitis
      following SBRT. The efficacy of CAM should be confirmed in prospective studies.

PMID- 29600056
TI  - Pulmonary embolism concurrent with lung cancer and central emboli predict
      mortality in patients with lung cancer and pulmonary embolism.
AB  - Background: Patients with lung cancer commonly experience pulmonary embolism
      (PE). The aim of the present study was to examine the clinical features of
      patients with lung cancer and PE and to investigate prognostic factors in these
      patients. Methods: This retrospective study divided patients with lung cancer and
      PE into a group of patients with PE diagnosed concomitantly with lung cancer
      (concurrent group) and a group with PE detected after lung cancer (sequential
      group), compared the clinical characteristics of patients in the two groups, and
      investigated prognostic factors in these patients. Results: The study population
      consisted of the concurrent group [27 patients (10.1%)] and the sequential group
      [240 patients (89.9%)]. The concurrent group exhibited higher percentages of
      stage I cancer at the diagnosis of PE [6 (22.2%) vs. 8 (3.3%), P<0.001] and right
      ventricular (RV) dilation on computed tomography (CT) [14 (51.9%) vs. 41 (17.1%),
      P<0.001], as well as lower rate of small cell carcinoma [1 (3.7%) vs. 49 (20.4%),
      P=0.036] than the sequential group. PE concurrent with lung cancer [hazard ratio
      (HR) =2.64, 95% confidence interval (CI): 1.57-4.43, P<0.001] and central PE (HR
      =1.46, 95% CI: 1.02-2.10, P=0.04) were independent predictors of mortality in
      patients with lung cancer and PE. Conclusions: PE concurrent with lung cancer is
      characterized by more severe PE and infrequent small cell carcinoma. PE
      concurrent with lung cancer and central emboli may be independent prognostic
      factors in patients with lung cancer and PE.

PMID- 29600057
TI  - Neutrophil-to-lymphocyte ratio as a prognostic marker in acute respiratory
      distress syndrome patients: a retrospective study.
AB  - Background: Acute respiratory distress syndrome (ARDS) is the leading cause of
      high mortality in intensive care units (ICUs) worldwide. An effective marker for
      prognosis in ARDS is particularly important given the absence of effective
      treatment strategies aside from small tidal volume ventilation. Previous studies
      identified an association between the neutrophil-to-lymphocyte ratio (NLR) and
      prognosis in critical patients. In this study, we explored the prognostic and
      predictive value of the NLR in ARDS patients. Methods: We retrospectively
      included 275 ARDS patients treated at a single institute from 2008 to 2015. After
      excluding patients with chronic lung disease, acute myocardial infarction and
      missing data, 247 patients were ultimately included in the analysis. Clinical
      characteristics and experimental test data, including the NLR, were collected
      from medical records at 24 hours after the ARDS diagnosis. Independent prognostic
      factors were determined by multivariate Cox regression analysis. Subgroup
      stratification was performed according to different factors, and the continuous
      factors were divided according to the median values. Results: The NLR in
      survivors was significantly lower than that in non-survivors (P<0.001). We took
      the median NLR value as the cut-off point and further divided all patients into a
      high NLR group (NLR >14) and a low NLR group (NLR <=14). We found that an NLR >14
      was associated with a shorter overall survival (OS) (P=0.005). In the
      multivariate Cox regression model, we further identified an NLR >14 as an
      independent prognostic factor for OS [hazard ratio (HR) 1.532, (95% CI, 1.095
      2.143), P=0.013]. Subgroup analysis showed that the prognostic value of the NLR
      was higher in hypertensive patients (P=0.009) and in patients with low red blood
      cell specific volume (P=0.013), high sodium (P=0.002) and high creatinine levels
      (P=0.017). Conclusions: The NLR is potentially a predictive prognostic biomarker
      in ARDS patients.

PMID- 29600058
TI  - Assessment of the mitral valve coaptation zone with 2D and 3D transesophageal
      echocardiography before and after mitral valve repair.
AB  - Background: Mitral valve (MV) coaptation is very important in MV repair patients.
      But accurate quantitation of the degree of MV coaptation remains challenging.
      This study aimed to evaluate the utility of two-dimensional (2D) and three
      dimensional (3D) transesophageal echocardiography (TEE) to assess MV coaptation
      before and after MV repair. Methods: Forty-eight patients [(age: 52.23+/-13.31
      years; 26 men (54.17%)] undergoing MV repair for mitral regurgitation (MR) were
      studied. We assessed the utility of 2D and 3D TEE to assess MV coaptation before
      and after MV repair. Complete conventional 2D and 3D TEE studies were performed,
      and the degree of the MV coaptation defect before and after surgery was assessed
      by measuring the MV coaptation length (CL) and length index (CLI) with 2D TEE,
      and the coaptation area (CA) and coaptation area index (CAI) with 3D TEE.
      Results: CL and CLI were measured successfully in 46 (95.83%) patients and CA and
      CAI in 39 (81.25%). Compared with preoperatively, postoperative CL, CLI, CA, and
      CAI were significantly increased (CL: 4.99+/-0.79 to 9.66+/-1.09 mm, P<0.05; CLI:
      9.30%+/-2.66% to 38.24%+/-3.82%, P<0.05; CA: 158.49+/-64.17 to 371.33+/-143.57
      mm2, P<0.05; CAI: 9.71%+/-2.76% to 36.24%+/-7.26%, P<0.05). Spearman's rank
      correlation analysis revealed that the CLI and CAI had a significant negative
      correlation with the degree of MR (r=-0.97, P<0.01; r=-0.92, P<0.01,
      respectively). Furthermore, Pearson's correlation analysis revealed that the CLI
      was significantly correlated with the CAI both preoperatively (r=-0.66, P<0.01)
      and postoperatively (r=-0.67, P<0.01). Conclusions: The coaptation variables
      increased significantly in patients undergoing MV repair. The CLI and CAI
      significantly correlated with MR severity. The CL and CLI determined with 2D TEE
      are more feasible than the CA and CAI determined with 3D TEE. Both 2D and 3D
      variables may complement each other for aiding MV repair. 2D CLI is an
      alternative to 3D CAI due to its simplicity.

PMID- 29600059
TI  - Video-assisted thoracic surgery for thymoma: long-term follow-up results and
      prognostic factors-single-center experience of 150 cases.
AB  - Background: The use of video-assisted thoracic surgery (VATS) in the treatment of
      thymoma is becoming more and more common. The aim of this study was to evaluate
      safety and effectiveness of thoracoscopic treatment of thymoma and, more
      importantly, to report long-term follow-up results of a large single-center
      cohort. Methods: A retrospective review of a prospective database was performed.
      In total, 150 patients who underwent VATS resection for thymoma at Peking
      University People's Hospital from April 2001 to November 2014 were
      retrospectively reviewed. Results: Average operation time was 140.1+/-54.2 min,
      median blood loss was 50 mL (range, 10-700 mL), median post-operative drainage
      time was 3 days (range, 1-11 days), and median length of post-op stay was 5 days
      (range, 2-20 days); 134 patients (89.3%) were followed up successfully. Median
      follow-up was 59.5 months (range, 2-187 months). Five- and 10-year recurrence
      free survival (RFS) rates of entire group were 96.5% and 94.4%, respectively; 5-
      and 10-year RFS rates for Masaoka stages I + II were 98.1% and 98.1%,
      respectively; 5- and 6-year RFS rates for Masaoka stage III were 90% and 60%,
      respectively. One case of recurrence in five Masaoka stage IV patients was
      observed, and 4-year RFS was 80%. Multivariable analysis indicated that
      recurrence tended to occur in Masaoka stages III + IV patients (P=0.037, HR
      =12.69, 95% CI: 1.17-138.22) and older patients had a lower risk of recurrence
      (P=0.029, HR =0.87, 95% CI: 0.77-0.99). Myasthenia gravis (MG) presented in 44
      patients (29.3%), of which 36 patients (81.8%) were followed up. Nine patients
      achieved complete remission, and 19 patients had symptom improvement after
      surgery. Overall response rate of MG was 77.8% (28/36). Conclusions: VATS was a
      safe and effective procedure for treatment of thymomas with satisfactory
      prognosis. MG with thymoma treated by VATS had comparable neurological outcome to
      that associated with the trans-sternal approach.

PMID- 29600060
TI  - Positive correlation between postoperative tumor recurrence and changes in
      circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical
      manipulation in non-small cell lung cancer.
AB  - Background: In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC)
      are shed and circulate to the peripheral blood through the pulmonary vein.
      Previously, CTC count in pulmonary venous blood (pvCTC) was shown to
      significantly increase after surgical manipulation. Therefore, we assessed the
      correlation between the changes in the pvCTC count (DeltapvCTC) and clinical
      outcomes. Methods: Consecutive patients with peripheral-type, NSCLC, who
      underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled
      prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the
      associated lobar pulmonary vein (PV), and was served for the quantitative
      evaluation of CTC using the CellSearch(r) system. The cut-off point of DeltapvCTC
      was determined according to clinical outcomes and DeltapvCTC using receiver
      operation characteristic (ROC) curve. Then the correlation between DeltapvCTC and
      clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In
      addition, the correlation between DeltapvCTC and perioperative variables was
      assessed. Results: A total of 30 patients were enrolled, tumor recurrence
      occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7
      patients had distant metastasis and 4 had local recurrence. The median DeltapvCTC
      was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation
      in 24 patients (80%). We divided patients into two groups based on DeltapvCTC
      with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant
      shorter time to distant metastasis (TDM) (P=0.0123) was observed in high
      DeltapvCTC group (DeltapvCTC >=119 cells/2.5 mL) than low DeltapvCTC group
      (DeltapvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall
      survival (OS) was significantly correlated with DeltapvCTC. Conclusions:
      Increasing pvCTC count during surgical manipulation was significantly correlated
      with postoperative distant metastasis in completely resected NSCLC patients.
      Significant shorter TDM was observed in patient with high DeltapvCTC group.

PMID- 29600061
TI  - Clinical applications of virtual navigation bronchial intervention.
AB  - Background: In patients with bronchial tumors, we frequently consider endoscopic
      treatment as the first treatment of choice. All computed tomography (CT) must
      satisfy several conditions necessary to analyze images by Synapse Vincent. To
      select safer and more precise approaches for patients with bronchial tumors, we
      determined the indications and efficacy of virtual navigation intervention for
      the treatment of bronchial tumors. Methods: We examined the efficacy of virtual
      navigation bronchial intervention for the treatment of bronchial tumors located
      at a variety of sites in the tracheobronchial tree using a high-speed 3
      dimensional (3D) image analysis system, Synapse Vincent. Constructed images can
      be utilized to decide on the simulation and interventional strategy as well as
      for navigation during interventional manipulation in two cases. Results: Synapse
      Vincent was used to determine the optimal planning of virtual navigation
      bronchial intervention. Moreover, this system can detect tumor location and
      alsodepict surrounding tissues, quickly, accurately, and safely. The feasibility
      and safety of Synapse Vincent in performing useful preoperative simulation and
      navigation of surgical procedures can lead to safer, more precise, and less
      invasion for the patient, and makes it easy to construct an image, depending on
      the purpose, in 5-10 minutes using Synapse Vincent. Moreover, if the lesion is in
      the parenchyma or sub-bronchial lumen, it helps to perform simulation with
      virtual skeletal subtraction to estimate potential lesion movement. By using
      virtual navigation system for simulation, bronchial intervention was performed
      with no complications safely and precisely. Conclusions: Preoperative simulation
      using virtual navigation bronchial intervention reduces the surgeon's stress
      levels, particularly when highly skilled techniques are needed to operate on
      lesions. This task, including both preoperative simulation and intraoperative
      navigation, leads to greater safety and precision. These technological
      instruments are helpful for bronchial intervention procedures, and are also
      excellent devices for educational training.

PMID- 29600062
TI  - Pulmonary metastasectomy in sarcoma-experiences with laser-assisted resection.
AB  - Background: Previous data suggest a survival benefit in well selected patients
      with extrathoracic sarcoma after pulmonary metastasectomy. Different techniques
      have been described for pulmonary metastasectomy; however laser-assisted surgery
      (LAS) was suggested to provide the best outcome in patients with higher numbers
      of metastases. Methods: Data were extracted from a prospectively maintained
      institutional database and a total of 83 patients who underwent pulmonary
      metastasectomy at our clinic in the last 11 years were identified. Results: We
      analyzed a total of 106 operations of which LAS was performed in 46 and
      conventional resection in 60 cases. Significantly more metastases were resected
      in the LAS group compared to the conventional group [median, interquartile range
      (IQR): 6.5 (2.0-11.0) vs. 1.0 (1.0-3.5); P<0.0001]. Despite this difference the
      number of tumor recurrences was similar in both groups [64% tumor recurrences in
      the LAS group and 58% in the conventional group, odds ratio (OR) =1.3, P=0.6].
      Furthermore, overall survival (OS) was comparable with a median survival of 77.6
      and 29.0 months and 2- and 5-year survival rates of 71% and 63% as well as 53%
      and 36% in the respective cohorts [hazard ratio (HR) =0.74, P=0.43]. Conclusions:
      Using LAS a significantly higher number of metastases were removed while
      producing similar long-term results as compared to patients treated by other
      techniques. Expectably, recurrence rates in metastasized sarcoma patients remain
      high with either surgical method. Future studies will have to evaluate possible
      advantages provided by LAS in a prospective manner.

PMID- 29600063
TI  - Independent long-term result of robotic thymectomy for myasthenia gravis, a
      single center experience.
AB  - Background: Robotic thymectomy has been suggested a feasible and safe approach
      for myasthenia gravis (MG). Few investigations have revealed the independent
      effect of robotic thymectomy without the confounding impact of immunosuppressive
      (IM) therapy. Methods: Between May 2009 and December 2012, robotic extended
      thymectomy was carried out for patients with diagnosis of MG. The clinical data,
      subsequent neurological therapy and postintervention status were collected.
      Results: Data of 37 cases was available for analysis. The mean follow-up was
      70.0+/-13.3 months. The median age was 40 years. Twelve (32.4%) patients kept
      free of IM therapy, and 25 (67.6%) patients accepted postoperatively. The overall
      5-year complete stable remission (CSR) rate was 40.6% and improvement rate was
      81.6%. The young (age <=40) displayed a significant better CSR rate (P=0.015) and
      a trend of better improvement rate (P=0.050) compared to the old (age >40).
      Patients without usage of IM therapy showed significant higher CSR rate (P=0.014)
      and improvement rate (P=0.024) compared to those with usage of IM therapy.
      Patients with Myasthenia Gravis Foundation of America (MGFA) classes I showed a
      trend of higher remission rate by multivariate analysis. No significant
      differences were found for the remission rate according to gender, pathology, and
      the duration of symptoms. Conclusions: The mono-therapy of robotic thymectomy may
      bring with a satisfactory long-term result for part of MG patients. Precision
      selection and individualized therapy are of the most importance.

PMID- 29600064
TI  - National adoption of video-assisted thoracoscopic surgery (VATS) lobectomy: the
      Italian VATS register evaluation.
AB  - Background: The expertise curve of video-assisted thoracoscopic surgery (VATS)
      lobectomies still stirs debate and controversy both because of the number of
      procedures to carry out and of the evaluation of the learning threshold. The
      purpose of our study was the examination of the variables related to the learning
      curve of the video-assisted approach, to establish what may be an expression of
      the technical maturity of the surgeon. Methods: The National Register for VATS
      lobectomy built in 2013 was used to collect data from 65 Thoracic Surgery Units.
      Out of more than 3,700 patients enrolled, only information from Units with >=100
      VATS lobectomies were retrospectively analysed. Unpaired Student's t-tests,
      Fisher's exact tests, Pearson's chi2 were applied as needed. Cumulative summative
      analysis and one-way ANOVA were used to identify the expertise curve of VATS
      lobectomy. Results: Ten institutions contributed a total of 1,679 patients, who
      were divided into three uniform groups according to the chronological sequence of
      surgery. The length of utility incision, the number of dissected lymph nodes and
      the operative time were not statistically significant (P=0.999, P=0.972 and
      P=0.307, respectively) among groups. Conversion to thoracotomy and postoperative
      air leaks occurred in 125 (7.44%) and 109 (6.49%) patients, gradually declined in
      Group 3 with statistical significance (P=0.048 and P=0.00086). Conclusions: The
      conversion rate and the percentage of air leaks seem to define the expertise of
      VATS lobectomy, being linked to the ability to manage more complicated surgical
      cases or intraoperative adverse events.

PMID- 29600065
TI  - High blood neutrophil-lymphocyte ratio associated with poor outcomes in miliary
      tuberculosis.
AB  - Background: It is difficult to predict the prognosis of miliary tuberculosis
      (TB). We hypothesized that blood neutrophil-lymphocyte ratio (NLR) is an
      indicator of inflammatory status to reflect independent prognostic significance
      in patients with miliary TB. The aim of this study is to investigate the
      relationship between NLR and outcome in miliary TB. Methods: We retrospectively
      collected data from patients diagnosed with miliary TB in a tertiary referral
      hospital between January 1995 and January 2016. Results: A total of 96 patients
      were enrolled. Seventeen patients (18%) died during hospitalization due to
      miliary TB, and 9 (9%) died additionally during the 1-year follow-up period.
      Eighteen patients (19%) were diagnosed with acute respiratory distress syndrome
      (ARDS). In multiple logistic regression analyses, increased NLR was associated
      with ARDS [adjusted odds ratio, 1.15; 95% confidence interval (CI), 1.03-1.28].
      By multivariate Cox regression analysis with adjustment of known prognostic
      factors including age, sex, body mass index, serum aspartate aminotransferase
      (AST), and hemoglobin, NLR was an independent predictor of in-hospital mortality
      [adjusted hazard ratio (aHR), 1.08; 95% CI, 1.03-1.13] and 1-year mortality (aHR,
      1.08; 95% CI, 1.05-1.12). Conclusions: Pre-treatment NLR at admission may be a
      useful biomarker for mortality and development of ARDS in patients with miliary
      TB.

PMID- 29600066
TI  - Comparison of closed-chest drainage with rib resection closed drainage for
      treatment of chronic tuberculous empyema.
AB  - Background: This study aimed to compare the efficacy of closed-chest drainage
      with rib resection closed drainage of chronic tuberculous empyema. Methods: This
      retrospective study reviewed 86 patients with tuberculous empyema in Shanghai
      Pulmonary Hospital from August 2010 to November 2015. Among these included
      patients, 22 patients received closed-chest drainage, and 64 patients received
      rib resection closed drainage. Results: The results showed that after intercostal
      chest closed drain treatment, 2 (9.09%) patients were recovery, 13 (59.09%)
      patients had significantly curative effect, 6 (27.27%) patients had partly
      curative effect, and 1 (4.55%) patient had negative effect. After treatment of
      rib resection closed drainage, 9 (14.06%) patients were successfully recovery, 31
      (48.44%) patients had significantly curative effect, 19 (29.69%) patients had
      partly curative effect, and 5 (7.81%) patients had negative effect. There was no
      significant difference in the curative effect (P>0.05), while the average
      catheterization time of rib resection closed drainage (130.05+/-13.12 days) was
      significant longer than that (126.14+/-36.84 days) in course of intercostal chest
      closed drain (P<0.05). Conclusions: This study had demonstrated that closed-chest
      drainage was an effective procedure for treating empyema in young patients. It
      was less invasive than rib resection closed drainage and was associated with less
      severe pain. We advocated closed-chest drainage for the majority of young
      patients with empyema, except for those with other diseases.

PMID- 29600068
TI  - Superior vena cava replacement combined with venovenous shunt for lung cancer and
      thymoma: a case series.
AB  - Background: Superior vena cava (SVC) replacement is infrequently performed and
      technically challenging in low-volume centers. Venovenous shunt (VVS) technique
      is used to reduce SVC pressure during SVC replacement and has not been well
      reported. This study aimed to add information on this subject and evaluate the
      surgical outcomes of patients who underwent SVC replacement combined with VVS in
      our center. Methods: A retrospective analysis of six patients who underwent SVC
      replacement combined with VVS from September 2011 to February 2017 was performed.
      Clinical characteristics, pathological features, operative characteristics,
      postoperative outcomes, and the survival of the six patients were reviewed.
      Results: There were four males and two females with a median age of 44 years
      (range, 35-69 years). There were three lung cancer patients and three thymoma
      patients at a stage from IIIA to IVA. Five patients underwent induction therapy.
      Complete resection was performed on five patients. One patient underwent internal
      VVS, and the other five patients underwent external VVS. Prosthesis grafts were
      employed in five cases and autologous pericardium in one case. Three patients
      underwent single-vein reconstruction, and the other three patients underwent
      double-vein reconstruction. The median SVC clamping time was 75 minutes. There
      were no postoperative deaths or major complications. All patients were alive at
      follow-up, and no thrombosis was found in any of the grafts. Conclusions: SVC
      replacement combined with VVS is technically feasible and safe. Although VVS
      technique is not a must, it may make SVC replacement safer in inexperienced
      centers. Surgery-based multidisciplinary treatment for selected patients with
      type T4 lung cancer and SVC involvement or thymoma and SVC involvement may
      achieve a favorable long-term outcome.

PMID- 29600067
TI  - Effect of chest tube size on pleurodesis efficacy in malignant pleural effusion:
      a meta-analysis of randomized controlled trials.
AB  - Background: Malignant pleural effusion (MPE) develops in approximately 50% of all
      patients with metastatic cancer. The efficacy of small- vs. large-bore chest tube
      for pleurodesis in patients with MPE is still not clear. Methods: We performed a
      meta-analysis to evaluate the efficacy and safety of chest tube size in the
      management of MPE. A systematic search of Medline (Ovid) and Embase (from 1980 to
      March 2016) was performed. Randomized clinical trials (RCTs) evaluating the
      effect of small (<=14 French) vs. large (>14 French) chest tube size on
      successful pleurodesis for patients with MPE. Of 708 potentially relevant
      publications, four matched the selection criteria and were included in the meta
      analysis. Results: Overall relative risk (RR) with 95% confidence intervals (CI)
      was pooled using a random-effects model. Heterogeneity was assessed using Q
      statistic (significant at P<0.1). In the 231 patients, the success proportion of
      pleurodesis as well as complication proportion were comparable between large and
      small chest tube groups with a pooled RR of 0.90 (95% CI, 0.77-1.05; P=0.19; I2
      =17.4%) and 0.95 (95% CI, 0.42-2.15; P=0.90; I2 =0.9%) respectively. Successful
      pleurodesis and complication proportion for small vs. large chest tubes were
      73.8% vs. 82.0% and 13.0% vs. 10.5%, respectively. Conclusions: This meta
      analysis suggests that small and large chest tubes are both effective treatment
      for MPE with similar successful pleurodesis and complication proportion. Further
      RCTs are needed to more clearly determine which size tube is superior.

PMID- 29600069
TI  - The management of chemical pleurodesis with viscum album in patients with
      persistent air leakage.
AB  - Background: Persistent air leak (PAL) after major pulmonary resection or involved
      with secondary lung disease is prevalent and associated with significant
      morbidity. Chemical pleurodesis is a practical therapeutic tool to manage the
      patients with PAL. Among various sclerosing substances, viscum album (fraxini) is
      considered effective and safe. The aim of this study was to evaluate the efficacy
      and safety of viscum album pleurodesis in patients with intractable prolonged air
      leakage. Methods: Between February 2013 and February 2015, 73 consecutive
      patients who underwent pleurodesis due to PAL were enrolled in this study.
      Pleurodesis was performed using 100 mg of viscum album (fraxini) at 1 time
      through the indwelling chest tube. Main studied outcomes were focused on success
      rate of pleurodesis assessed on chest radiography and cessation of the air leak
      after procedure. Results: The study population was predominantly male (n=64,
      87.7%). The overall success rate was 90.4%. One patient died of pneumonia not
      related to the viscum album pleurodesis. The mean length of stoppage to air
      leakage was 28.00+/-22.19 hours. The mean duration of chest tube drainage after
      pleurodesis was 2.78+/-1.35 days. The mean number of pleurodesis was 1.38+/-0.75.
      Thirty-six patients (49.3%) complained of chest pain requiring a prescription for
      pain control. There were no major relevant complications or mortalities.
      Conclusions: Air leaks remain an important cause of morbidity. This viscum album
      pleurodesis could be considered as an option for the treatment of prolonged air
      leak patients, associated with acceptable side effects.

PMID- 29600070
TI  - Deep sternal wound infection after cardiac surgery: a comparison of three
      different wound infection types and an analysis of antibiotic resistance.
AB  - Background: Deep sternal wound infection (DSWI) is a severe complication
      following cardiac surgery. We compared epidemiology, clinical features, and
      microbiology of three types of DSWI and examined the antibiotic resistance in
      DSWI patients. Methods: From 2011 to 2015, 170 adult post-cardiac surgery DSWI
      patients were recruited for this study and underwent the pectoralis major muscle
      flap transposition in our department. Results: Of 170 adult patients with DSWI
      (mean age of 54 years), the majority (99 patients, 58.2%) had type II DSWI. The
      three types of DSWI patients showed significant differences in terms of gender,
      smoking history, chronic obstructive pulmonary disease (COPD), length of
      intensive care unit (ICU) stay, and hospitalization cost (P<0.05). The most
      common symptoms of DSWI patients were fever and wound dehiscence accompanied by
      purulent secretions. Types I and II DSWI were more frequently associated with
      hypoproteinemia and high leucocyte count (P<0.05). Microbiological diagnosis was
      available for 77 of 170 patients (45.3%). Of 157 pathogens detected, 87 (55.4%)
      species of gram negative bacilli were identified and most commonly were
      Pseudomonas aeruginosa (25.5%) and methicillin-susceptible Staphylococcus aureus
      (20.4%). However, no statistically significant microbiological differences among
      the three DSWI types were observed (P>0.05). Notably, P. aeruginosa isolates
      showed 100% resistance to cefazolin and cefuroxime. Meanwhile, the resistance
      rate of Acinetobacter baumannii isolates to commonly used antibiotics was greater
      than 70%, while resistance rates of staphylococcus to penicillin-G were 100% and
      to clindamycin were over 70%. No isolates were resistant to vancomycin,
      linezolid, and tigecycline. Conclusions: Three types of DSWI exhibit differences
      in epidemiology and clinical features. P. aeruginosa and S. aureus are the most
      common pathogens in DSWI patients and antibiotic resistance is a serious concern
      in these patients. Therefore, prevention and treatment of DSWI should be closely
      tailored to clinical features, local microbiological characteristics, and
      resistance patterns of commonly encountered pathogens.

PMID- 29600071
TI  - Prognostic significance of histologic classification and tumor disappearance rate
      by computed tomography in lung cancer.
AB  - Background: We investigated the prognostic value of the International Association
      for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European
      Respiratory Society (ERS) classification and assessed the relationship between
      pathologic invasiveness and tumor disappearance rate (TDR) in lung adenocarcinoma
      with ground-glass opacity (GGO). Methods: We reviewed data from 202 consecutive
      patients operated on between 2000 and 2009 for clinical T1-2N0 lung
      adenocarcinoma with GGO and reclassified their histologic subtypes according to
      the IASLC/ATS/ERS classification. Thirty-nine patients had adenocarcinoma in situ
      (AIS), 29 minimally invasive adenocarcinoma (MIA), 75 lepidic predominant
      invasive adenocarcinoma (LPA), and 59 non-lepidic predominant invasive
      adenocarcinoma (NLPA). Survival outcomes were compared according to histologic
      subtype and TDR. Results: The mean age was 58 years and 101 patients (50%) were
      male. Lobectomy was performed in 161 patients (79.7%), wedge resection in 34
      (16.8%), and segmentectomy in 7 (3.5%). Patients with AIS, MIA, and LPA had
      significantly smaller tumor sizes, earlier pathologic T stages, and lower
      incidences of lymphatic/pleural invasion than those with NLPA. The 5-year
      recurrence-free survival (RFS) rates were 95.1%, 94.5%, and 87.6% in the AIS +
      MIA, LPA, and NLPA groups, respectively (P=0.029). Tumors with a TDR>75% were
      associated with lepidic predominant histologic subtype and less pathologic
      invasiveness. The 5-year RFS rates were 97.4% in tumors with a TDR >75% and 87.8%
      in tumors with a TDR <=75% (P=0.0009). Conclusions: Histologic subtype according
      to the IASLC/ATS/ERS classification and TDR both correlated with pathologic
      invasiveness and predicted survival in patients with lung adenocarcinoma with
      GGO.

PMID- 29600072
TI  - Aberrant status and clinicopathologic characteristic associations of 11 target
      genes in 1,321 Chinese patients with lung adenocarcinoma.
AB  - Background: The aberrant status of target genes and their associations with
      clinicopathologic characteristics are still unclear in primary lung
      adenocarcinoma. Methods: The common mutations and translocations of nine target
      genes were evaluated in 1,247 specimens of surgically-resected primary lung
      adenocarcinoma. Immunohistochemistry was used to analyze the expressions of
      programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in 731 specimens. The
      frequency of the aberrations and their associations with clinicopathologic
      characteristics were analyzed. Results: Overall, 952 (76.3%) of 1,247 patients
      harbored at least one target mutation or translocation: epidermal growth factor
      receptor (EGFR) (729, 58.5%), v-Ki-ras2 Kirsten rat sarcoma viral oncogene
      homolog (KRAS) (83, 6.7%), human epidermal growth factor receptor 2 (HER2) (82,
      6.6%), anaplastic lymphoma kinase (ALK) (23, 1.8%), phosphoinositide-3-kinase
      catalytic alpha polypeptide (PIK3CA) (20, 1.6%), Ret proto-oncogene RET (15,
      1.2%), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) (12, 1.0%), B-raf
      proto-oncogene (BRAF) (9, 0.7%), neuroblastoma RAS viral (v-ras) oncogene homolog
      (NRAS) (3, 0.2%). Fourteen (1.9%) of 731 patients were PD-1 positive and 95
      (13.0%) were PD-L1 positive in tumor cells. In men and smokers, there were more
      frequent KRAS mutations (both P<0.001) and PD-L1 positive tumors (P<0.001,
      P=0.005, respectively), and less frequent EGFR mutations (P=0.049, <0.001,
      respectively). In ground-glass opacity (GGO) or ground-glass nodules (GGN), there
      were more HER2 (P=0.033) but less EGFR (P=0.025) and PIK3CA mutations (P=0.012),
      and ALK translocations (P=0.014). EGFR (P<0.001), KRAS mutations (P=0.004) and PD
      L1 positive tumors (P=0.046) were more frequent in older patients, while HER2
      (P<0.001), ALK (P=0.005) and ROS1 aberrations (P=0.044) were less frequent.
      Invasive mucinous adenocarcinoma was significantly associated with KRAS and ALK
      aberrations (both P<0.001), while solid predominant adenocarcinoma was associated
      with ROS1 translocations (P=0.036) and PD-L1 expression (P<0.001). KRAS, HER2,
      and ALK aberrations were scarce in patients with EGFR mutations (all P<0.001),
      while PD-L1 positive tumors positively correlated with ALK translocations
      (P=0.031) and negatively correlated with HER2 mutations (P=0.019). Conclusions:
      Most patients with primary lung adenocarcinoma harbored target gene aberrations.
      The frequency of each alteration differed in patients depending on
      clinicopathologic characteristics.

PMID- 29600073
TI  - MicroRNA expression profile in primary lung cancer cells lines obtained by
      endobronchial ultrasound transbronchial needle aspiration.
AB  - Background: Novel cancer biomarkers like microRNA (miRNA) are promising tools to
      gain a better understanding of lung cancer pathology and yield important
      information to guide therapy. In recent years, new less invasive methods for the
      diagnosis and staging of NSCLC have become key tools in thoracic oncology and the
      worldwide spread of endobronchial ultrasound transbronchial needle aspiration
      (EBUS-TBNA). However, appropriate specimen handling is mandatory to achieve
      adequate results and reproducibility. The aim of this single centre prospective
      study was to evaluate the feasibility of a complete miRNA expression profile in
      fresh NSCLC cell lines obtained by EBUS-TBNA. Methods: Patients with proven NSCLC
      underwent EBUS-TBNA for the diagnosis of suspect lymph node metastasis, and
      cytological specimens were collected for epithelial cell culture and miRNA
      expression analysis. To validate the miRNA expression profile, we compared the
      results from EBUS-TBNA NSCLC specimens with those obtained from formalin-fixed
      paraffin-embedded (FFPE) mediastinoscopy specimens. Results: Analysis of the
      miRNA expression profiles of three independent EBUS-TBNA-derived primary cell
      lines allowed the screening of 377 different human miRNAs. One hundred and fifty
      miRNAs were detected in all cell lines. Analysis of the miRNA expression profile
      in mediastinoscopy specimens showed a strong similarity in the clusters analysed.
      Conclusions: The miRNA expression profile is feasible and reliable in EBUS-TBNA
      specimens. Validation of this protocol in fresh cytological specimens represents
      an effective and reproducible method to correlate translational and clinical
      research.

PMID- 29600074
TI  - Presence of pleural adhesions can predict conversion to thoracotomy and
      postoperative surgical complications in patients undergoing video-assisted
      thoracoscopic lung cancer lobectomy.
AB  - Background: The purpose of our cohort study was to investigate the effects of
      pleural adhesions on perioperative outcomes in patients undergoing video-assisted
      thoracoscopic surgery (VATS) lobectomy for non-small-cell lung cancer (NSCLC).
      Methods: We performed a single-center retrospective analysis on the prospectively
      maintained dataset at our unit from February 2014 to November 2015. Patients were
      divided into two groups (Group A: presence of pleural adhesions; Group B: absence
      of pleural adhesions) according to our grading system of pleural adhesions when
      entering the chest cavity. Demographic differences in perioperative outcomes
      between these two groups were initially estimated. A multivariate logistic
      regression analysis was then performed to confirm the predictive value of the
      presence of pleural adhesions. Results: A total of 593 NSCLC patients undergoing
      VATS lobectomy were enrolled. The conversion and postoperative morbidity rates
      were 3.2% and 29.2%, respectively. There were 154 patients with pleural adhesions
      (Group A) and 439 patients without pleural adhesions (Group B). Group A patients
      had significantly higher rates of conversion to thoracotomy (9.1% vs. 1.1%;
      P<0.001) and surgical complications (24.0% vs. 14.4%; P=0.006) than those of
      Group B patients. No significant difference was found in the overall morbidity
      and cardiopulmonary complication rates between these two groups. The presence of
      pleural adhesions was also significantly associated with the prolonged length of
      chest tube drainage (log-rank P<0.001) and length of stay (log-rank P=0.032).
      Finally, the presence of pleural adhesions was identified as an independent risk
      factor for conversion to thoracotomy [odds ratio (OR) =5.49; P=0.003] and
      surgical complications (OR =1.94; P=0.033) by multivariate logistic-regression
      analyses. Conclusions: Presence of pleural adhesions can predict conversion to
      thoracotomy and postoperative surgical complications in patients undergoing VATS
      lobectomy for NSCLC. Our study calls for an internationally accepted grading
      system for the presence of pleural adhesions to stratify the surgical risk.

PMID- 29600075
TI  - Sarcopenia is a predictor of outcomes after lobectomy.
AB  - Background: As screening for lung cancer rises, an increase in the diagnosis of
      early stage lung cancers is expected. Lobectomy remains the standard treatment,
      but there are alternatives, consideration of which requires an estimation of the
      risk of surgery. Sarcopenia, irrespective of body mass index, confers a worse
      prognosis in many groups of patients including those undergoing surgery. Here we
      examine the association of muscle mass with outcomes for patients undergoing
      lobectomy. Methods: Consecutive patients undergoing lobectomy were
      retrospectively reviewed. Preoperative computed tomography scans were reviewed,
      and cross-sectional area of the erector spinae muscles and pectoralis muscles was
      determined and normalized for height. Univariate and multivariate analyses were
      then done to examine for an association of muscle mass with morbidity and short-
      and long-term mortality. Results: During the study period, there were 299
      lobectomies, 278 of which were done by video assisted thoracoscopic surgery. The
      average age of the patients was 67.5+/-10.6 years. Overall complication rate was
      52.2%, pneumonia rate was 8.7%, and the 30-day mortality rate was 1.3%. Mean
      height adjusted-erector spinae muscle cross-sectional area was 10.6+/-2.6 cm2/m2,
      and mean height adjusted-pectoralis muscle cross sectional area was 13.3+/-3.8
      cm2/m2. The height adjusted cross sectional areas of the erector spinae and
      pectoralis muscles were not associated with overall complication rate, rate of
      pneumonia, readmission, or intensive care unit length of stay. The height
      adjusted-erector spinae muscle cross sectional area was inversely correlated with
      30-day mortality risk, odds ratio 0.77 (95% CI, 0.60-0.98, P=0.036). Mean length
      of stay was 7.0 days (95% CI, 5.5-8.4 days). Multivariate analysis demonstrated a
      significant inverse association of the height adjusted-erector spinae muscle
      cross sectional area with length of stay (P=0.019). Conclusions: The height
      adjusted-erector spinae muscle cross sectional area was significantly associated
      with 30-day mortality and length of stay in the hospital. Measurement of muscle
      mass on preoperative computed tomography imaging may have a role to help predict
      risk of morbidity and mortality prior to lobectomy.

PMID- 29600076
TI  - Risk factors and methylenetetrahydrofolate reductase gene in congenital heart
      disease.
AB  - Background: Congenital heart disease (CHD), which involve congenital
      cardiovascular malformations that occur during an embryo stage, may be the result
      of a complex interaction between genetic factors and environmental factors. The
      homozygous 677 T/T MTHFR gene and potential factors have been associated with
      CHD. Our objective was to study associations between potential environmental risk
      factors and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in
      CHD. Methods: A total of 346 children with CHD and 237 healthy children were
      recruited. Their parents were also enlisted in the study and interviewed face-to
      face to identify potential environmental risk factors. The MTHFR genotype was
      analyzed by restriction fragment length polymorphism (RFLP). Interactions between
      environmental risk factors and MTHFR gene polymorphisms were evaluated by the
      relative excess risk due to interaction (RERI), the attributable proportion due
      to interaction (AP), and the synergy index (S). Results: There were significant
      differences in the occupational statuses of the mothers and their levels of drug
      exposure during gestation between the controls and the cases (P<0.05). These
      differences significantly increased offspring CHD risk (occupation: OR =5.45, 95%
      CI: 3.46-8.58; drug exposure: OR =4.91, 95% CI: 2.18-11.09). The frequency of the
      MTHFR gene 677 TT polymorphism in the mothers who had offspring with CHD was
      significantly different from that in the non-CHD controls (P<0.05). The frequency
      of this polymorphism also significantly differed between the children with CHD
      and the control group (P<0.05). An interaction was identified between the
      presence of the homozygous 677 TT genotype in the children and the mothers'
      occupational statuses (RERI =9.43, CI: 0.06-18.91). Conclusions: A significant
      interaction was found between the homozygous 677 T/T MTHFR gene in children and
      the maternal occupational status and level of drug exposure during gestation.
      Avoiding or reducing the exposure of the risk factors mentioned above,
      strengthening pre-pregnancy checkups and guidance might help to reduce the risk
      of CHD.

PMID- 29600077
TI  - Esophageal cancer in elderly patients: a population-based study.
AB  - Background: As the aging issue and increased elderly esophageal cancer (EC)
      patients, we sought to study the clinical characteristics, treatment modality and
      outcomes of EC patients 70 years or older compared with those younger than 70
      years old. Methods: The national surveillance, epidemiology, and end results
      (SEER) database for the period from 1973 to 2013 was analyzed. The patient and
      treatment characteristics were compared between the age groups. Multivariate Cox
      proportional hazard regression analyses were also performed to identify
      independent prognostic factors. Propensity-score matching analyses (PSA)
      regarding survival after different treatments were also performed in locoregional
      EC. Results: Compared with the younger group, patients 70 years or older were
      characterized by having a higher proportion of patients with female gender, white
      race, localized disease, non-adenocarcinoma and without any treatment, as well as
      inferior overall survival (OS) [hazard ratio (HR), 1.324] and EC-specific
      survival (HR, 1.270). In addition, older patients shared same independent
      prognostic factors with younger patients, including age, histology and race.
      Specifically, compared with those receiving no intensive treatments, surgery
      alone (HR, 0.342), both surgery and RT (HR, 0.323) and RT only (HR, 0.525) were
      favorable among elderly patients, as confirmed by both multivariate adjustment
      and PSA. Conclusions: Compared to younger EC patients, those 70 years or older
      showed distinctive clinical characteristics and inferior survival. Despite
      showing a higher proportion of localized disease, patients 70 years or older were
      less likely to be subjected to surgery or/and RT. Thus, the role of intensive
      treatments, which were identified as favorable factors among elderly patients in
      this study, warrants further investigation.

PMID- 29600078
TI  - Predicting malignancy of pulmonary ground-glass nodules and their invasiveness by
      random forest.
AB  - Background: The purpose of this study was to develop a predictive model that
      could accurately predict the malignancy of the pulmonary ground-glass nodules
      (GGNs) and the invasiveness of the malignant GGNs. Methods: The authors built two
      binary classification models that could predict the malignancy of the pulmonary
      GGNs and the invasiveness of the malignant GGNs. Results: Results of our
      developed model showed random forest could achieve 95.1% accuracy to predict the
      malignancy of GGNs and 83.0% accuracy to predict the invasiveness of the
      malignant GGNs. Conclusions: The malignancy and invasiveness of pulmonary GGNs
      could be predicted by random forest.

PMID- 29600079
TI  - A technique of minimally invasive aortic valve replacement: an alternative to
      transcatheter aortic valve replacement (TAVR).
AB  - Minimally invasive aortic valve replacement (AVR) is increasingly being adopted
      worldwide, in which a right mini-thoracotomy (RT) approach plays an important
      role. Here we reported a novel technique of AVR via RT using sutureless
      prosthesis, without rib division or groin incision. Surgical access was performed
      through an anterior right thoracotomy with 5-cm skin incision placed in the third
      intercostal space. Percutaneous femoral-femoral cardio-pulmonary bypass (CPB) was
      applied under fluoroscopy guidance to avoid groin incision. A 5-mm stab incision
      was made in the right chest wall for aortic cross-clamping. A sutureless
      bioprosthetic valve was utilized in the limited operative field, which reduced
      the cross-clamp and CPB time. The patient was discharged on post-operative day 2,
      without obvious cross-valvar gradient, and with no pain or other complication.
      This report offers a more minimally invasive approach to AVR with proven durable
      valves, which can benefit high-risk patients.

PMID- 29600080
TI  - Emergency drain for post pneumonectomy bronchopleural fistula: a drain placement
      technique based on the siphon principle.
AB  - Post pneumonectomy bronchopleural fistula (BPF) is a life-threatening
      complication requiring pleural cavity drainage to avoid acute mediastinal shift
      and contralateral aspiration pneumonia. Chest drain insertion in this situation
      may be technically difficult because of drastic anatomical changes such as
      mediastinal dislocation, diaphragm elevation and, sometimes, massive subcutaneous
      emphysema. In addition, the most important part of the pleural cavity to be
      drained is the costophrenic recess that is scarcely drained by a standard chest
      tube with its tip aiming high and upwards. We propose a safe, simple and
      effective technique based on the siphon principle to drain the lowest part of the
      pleural cavity.

PMID- 29600081
TI  - Intramedullary reinforcement of sternal fixation with autologous xiphoid tenon.
AB  - Minimally invasive cardiac surgery through a partial sternotomy or a
      ministernotomy is popular. However, the transverse nonunion of the sternum will
      be a potential complication. Valid and valuable techniques have been introduced
      for securing the sternotomy fixation. Most of them are focused on the materials
      or methods for extrinsic reinforcement. A new concept, focused on the
      intramedullary reinforcement of the sternal fixation, was designed by
      incarcerating a cancellous portion of the autologous xiphoid in the marrow space
      of the inter-segmental junction of the partial sternotomy. This autologous
      xiphoid tenon method is simple, reliable, and reproducible without additional
      requirement of device implantation or an iliac incision for the bone grafting.

PMID- 29600082
TI  - Four arms robotic-assisted pulmonary resection-right lower/middle lobectomy: how
      to do it.
AB  - In the last few years, robotic approach for anatomic lung resection has brought
      an innovative development in minimally invasive thoracic surgery. This study
      analyzes the technical aspects of performing the hilar dissection for a lobectomy
      via robotic approach. With a detailed step-by-step description and essential tips
      and videos, in this paper, we report the procedure to carry out a four-arm
      robotic middle and lower lobectomy.

PMID- 29600084
TI  - Surgical approaches in patients with oligometastatic non-small cell lung cancer.
AB  - In recent years, retrospective analyses have suggested that an oligometastatic
      state could exist, but the best evidence to date that a temporary oligometastatic
      disease exists for lung cancer mainly derives from the survival data on
      retrospective patients underwent surgical resection of a single M1 site and all
      intrathoracic disease. The critical determinates of long-term survival include
      definitive treatment of the primary non-small cell lung cancer (NSCLC), a single
      organ site of synchronous or metachronous disease, a long disease-free interval
      between treatment of the primary NSCLC and development of metastases, and the
      absence of intrathoracic lymph node (N0) disease. The ongoing development of
      innovative approaches to local therapy and treatment directed to the
      oligometastatic sites should be defined in future studies.

PMID- 29600083
TI  - Influence of estrogen in non-small cell lung cancer and its clinical
      implications.
AB  - Lung cancer (LC) is the leading cause of cancer death in men worldwide and has
      significantly increased in women. Differences in non-small cell lung cancer
      (NSCLC) behavior, prognosis, and response to treatment have been reported by sex
      and hormonal status, with premenopausal women presenting the worst prognosis
      compared to postmenopausal women and men. Additionally, the use of hormonal
      replacement therapy significantly increases NSCLC mortality; supporting the role
      of estrogen signaling in the pathogenesis of LC. The mechanisms by which estrogen
      promotes lung carcinogenesis have not been fully elucidated. Estrogen, through
      its receptor, can stimulate LC cell proliferation, death resistance,
      angiogenesis, migration and metastasis. Estrogen also induces expression of pro
      inflammatory proteins and ligands that promote tumor evasion, suggesting that
      estrogen might modify the microenvironment and anti-tumor immune response. Recent
      reports have shown an interaction between the epidermal growth factor receptor
      (EGFR) pathway and estrogen signaling in lung adenocarcinoma, whence, combined
      treatment based on tyrosine kinase inhibitors (TKIs) and antiestrogen therapy is
      beginning to be evaluated. This review focuses on the differences in NSCLC
      behavior by sex and hormonal status, highlighting the role of estrogen and its
      receptors in lung carcinogenesis and LC prognosis. Due to the importance of
      estrogen in NSCLC development and progression we finally discuss the potential of
      antiestrogen therapy in LC treatment and show the results from preclinical and
      clinical trials.

PMID- 29600085
TI  - Current role of standardized uptake valuemax-derived ratios in N2 fluorine-18
      fluorodeoxyglucose positron-emission tomography non-small cell lung cancer.
AB  - Mediastinal staging is a crucial moment in management of non-small cell lung
      cancer (NSCLC) patients. In integrated pathways, 18-fluorine fluorodeoxyglucose
      positron-emission tomography (18F-FDG-PET/CT) is an indispensable imaging
      resource with its peculiarities and its limitations. A critical review of work up
      protocols would certainly help to standardize procedures with important
      reflections also on the diagnostic value of this examination. In this regard, new
      semi-quantitative and semi-qualitative indexes have been proposed with the aim of
      increasing the accuracy of 18F-FDG-PET/CT in mediastinal lymph node staging.
      These latter, such as SUVn/t and SUV indexes, seem to overcome the problem of
      spatial resolution and discrimination of malignancy by endorsing a new predictive
      and prognostic role.

PMID- 29600087
TI  - Diagnostic and therapeutic challenges in managing persistent air leaks.
AB  - Persistent air leak (PAL) is a common and challenging condition associated with
      increased morbidity and mortality, intensive care unit admission, and prolonged
      hospital stay. Multiple medical and surgical approaches have been developed to
      manage PAL. Depending on the etiology of PAL, surgical management may be
      effective and usually performed using video-assisted thoracoscopic surgery
      (VATS). Medical management is less invasive and consists of pleural or
      bronchoscopic methods. The non-surgical techniques for the management of PAL have
      not been investigated in large prospective studies, and so their use is mostly
      guided by observational data. Specifically, the role of intrabronchial valve
      (IBV) placement for PAL has been the subject of an ever-increasing number of case
      reports and series documenting successful deployment of IBVs for both surgical
      and medical PAL. In this case-based discussion, we describe three patients with
      non-surgical PAL who were managed using multiple modalities, including both
      surgical and medical approaches. These cases illustrate the challenges in
      identifying the location of the air leak and in the application of various
      therapeutic options.

PMID- 29600088
TI  - The J-waves of hypothermia.
AB  - Prominent J-waves are observed in several clinical conditions many of which are
      highly arrhythmogenic and may lead to ventricular fibrillation (VF) and/or sudden
      cardiac death. We present the case of a 34-year-old male patient with
      hypothermia. Prominent J-waves (Osborn waves) and prolonged QT interval was
      evident in nearly every lead. Early recognition of these arrhythmogenic
      electrocardiogram (ECG) findings and treatment of hypothermia is important to
      minimize the risk of arrhythmic events.

PMID- 29600086
TI  - Exercise training in pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is characterized by a continuous increase
      in pre-capillary pulmonary vascular resistance (PVR) with a progressive reduction
      of cardiac output (CO). Similar to what occurs in left heart failure (HF), this
      represents the initial phase of a syndrome characterized by the progressive
      development of dyspnea and fatigue with increasing deterioration of exercise
      tolerance. Although the therapies introduced in the last two decades have
      determined a significant improvement of the clinical conditions of PAH patients,
      they have a little impact on exercise capacity and prognosis. However, as
      previously demonstrated for HF, recent pilot studies have reported that physical
      and respiratory rehabilitation may have a specific role in the management of PAH.
      Despite potential risks, so far all studies agree that exercise training (ET)
      improves exercise capacity, quality of life (QoL), muscle function and pulmonary
      circulation. We will review the pathophysiological mechanisms underlying the
      functional incompetence of PAH patients, the effects of ET on clinical and
      functional parameters, the selection criteria for inclusion of patients in a
      training program, the suggested monitoring of beneficial effects or possible side
      effects induced by ET. Finally, we discuss of the possible exercise induced
      amelioration of prognosis in PAH.

PMID- 29600089
TI  - Diagnostic criteria for obstructive sleep apnea: time for reappraisal.

PMID- 29600090
TI  - Global Alliance against Chronic Respiratory Diseases (GARD) Brazil success case:
      overcoming barriers.

PMID- 29600091
TI  - Prof. Yih-Sharng Chen: a new era-to breakthrough the old times.

PMID- 29600092
TI  - Prof. Jang-Ming Lee: single-incision minimally invasive esophagectomy (MIE),
      better recovery for patients.

PMID- 29600093
TI  - Prof. Miguel A. Cuesta: my experience to being a surgeon on gastrointestinal
      surgery (specially in esophageal cancer).

PMID- 29600094
TI  - Prof. Pierluigi Stefano: new options for the surgical treatment of aortic valve.

PMID- 29600095
TI  - Prof. Kenji Suzuki: craziness on the road to success.

PMID- 29600096
TI  - An adult case of plastic bronchitis: a rare and multifactorial disease.
AB  - Plastic bronchitis is a rare and potentially fatal disease. Mainly a disease of
      the pediatric age, a few adult cases occurring after cardiac surgery have been
      described. We describe a case of a 41-year-old man suffering from several
      episodes of acute dyspnea and cough with expectoration of mucous plugs in the
      context of chronic allergic airway inflammation. We believe that the occurrence
      of plastic bronchitis in adulthood should not be overlooked particularly in
      patients with chronic inflammatory lung disease.

PMID- 29600097
TI  - Concurrent thymic carcinoma and middle lobe syndrome.
AB  - Surgery is one of the first-line treatments for thymic carcinoma. Middle lobe
      syndrome which is irresponsive to conservative therapies also calls for surgical
      intervention. We reported the case of a 65-year-old male who was diagnosed with
      coexistent thymic carcinoma and non-obstructive middle lobe syndrome. Before the
      operation, we took measures including repeated sputum examination, physical
      therapy, postural sputum drainage and bronchodilator inhalation. After removal of
      the mediastinal neoplasm, venous antibiotics were used to prevent pneumonia. The
      preexistent cough with purulent expectoration still lasted, but no pulmonary
      infection occurred. Our report indicates that middle lobe syndrome may not
      increase respiratory complications after midline sternotomy if it receives proper
      treatments before the operation. For patients with concurrent thymic carcinoma
      and persistent middle lobe atelectasis, the thymic tumor might be treated with
      priority to increase the chance of complete resection.

PMID- 29600098
TI  - Interrupted right-sided aortic arch: performance of umbilical xenograft after
      primary neonatal corrective surgery.
AB  - Interrupted aortic arch (IAA) associated with right-sided aorta descendens is a
      rare congenital malformation. We present a case of a female patient who was
      diagnosed with type B IAA and received primary corrective surgery as a neonate. A
      bovine umbilical vascular graft was used to establish aortic arch continuity.
      Thirty-nine years later the same patient presents with graft-dilatation and a
      distal aneurysm requiring a surgery. This case shows a late complication of a
      biological xenograft in term of long-term material performance. Moreover, it
      highlights the necessity for regular follow-ups in order to detect and treat late
      onset complications respectively.

PMID- 29600099
TI  - Massive pericardial effusion after Nuss procedure: to drain or not to drain?
AB  - A 11-year-old boy presented with refractory fever and dyspnoea after Nuss
      procedure. Massive pericardial effusion was detected on computer tomography scan
      performed under corticosteroid cover for his asthmatic history. With rapid
      clinical improvement following corticosteroids, a clinical diagnosis of post
      pericardiotomy syndrome (PPS) was made. Following a course of oral prednisolone,
      serial blood test and echocardiogram showed gradual resolution of inflammation
      and pericardial effusion. This rarely-reported case serves as a poignant reminder
      to PPS after Nuss procedure as a cause of febrile massive pericardial effusion.
      Early therapeutic trial of corticosteroids may prevent clinical deterioration,
      and have invasive pericardial drainage avoided.

PMID- 29600100
TI  - Unusual cardiac paraganglioma mimicking an atypical carcinoid tumor of the lung.
AB  - We present a case of unusual cardiac paraganglioma (PG) initially misdiagnosed as
      atypical carcinoid tumor of the lung and discuss key clinical and pathologic
      characteristics that guide surgical management of these rare chromaffin cell
      tumors. A 64-year-old female with persistent cough and back pain was found to
      have a 4 cm * 3 cm mass abutting multiple cardiopulmonary structures. A biopsy
      was performed at an outside institution and pathology reported "atypical
      neuroendocrine carcinoma, consistent with carcinoid". The patient was transferred
      to our institution and pericardial resection with right pneumonectomy was
      performed to excise the tumor. Histology of the mass was that of PG with multiple
      ethanol embolizations. Immunohistochemical examination revealed that type I
      (chief) cells were positive for neuroendocrine markers (chromogranin A and
      synaptophysin), while type II (sustentacular) cells were positive for S100. There
      was no evidence of atypical carcinoid tumor in the lung. PG is an entity of
      chromaffin cell tumors that often affects the adrenal glands and carotid body. PG
      rarely occurs in the thoracic region, accounting for just 1-2% of all PG. Proper
      diagnosis of cardiac PG is challenging owing to its rare prevalence, subtle
      symptoms of presentation, and the neuroendocrine histopathological features it
      shares with atypical carcinoids. These tumors are typically benign and are best
      treated by surgical resection. Our report examines the approach to appropriate
      diagnosis of cardiac PG vs. atypical carcinoid, preoperative management, and
      surgical treatment by describing successful resection through thoracotomy without
      the use of cardiopulmonary bypass.

PMID- 29600101
TI  - Approach to resection of sternoclavicular tumor abutting the common carotid
      artery in irradiated field.
AB  - Head and neck cancer recurrence at the sternoclavicular junction (SCJ) in
      irradiated field poses a special challenge in terms of surgical planning. We
      herein present a case of tonsillar squamous cell cancer recurrence at the SCJ in
      a patient with history of tracheostomy and head and neck radiation. We describe
      our preoperative planning for vascular control and possible reconstruction as
      well as our approach for safe resection.

PMID- 29600102
TI  - Pneumatosis intestinalis after lung transplantation for pulmonary graft-versus
      host disease.
AB  - Pneumatosis intestinalis, which could complicate a spectrum of clinical
      conditions ranging from benign to life-threatening, is a rarely encountered
      complication after lung transplantation (LT). We describe two cases in which PI
      developed as a complication following LT for pulmonary graft-versus-host disease
      (GVHD) after hematopoietic stem cell transplantation (HSCT). In addition to the
      long-term immunosuppression administered for pulmonary GVHD, the intense
      immunosuppression needed after LT might increase the risk of PI in lung
      transplant recipients after HSCT. Conservative therapy should be considered for
      the treatment of PI developing after LT.

PMID- 29600103
TI  - Report of a lung carcinoma extended to the left atrium through pulmonary vein.
AB  - Lung cancers may extend along or grow through the pulmonary veins to invade or
      lie within the left atrium (LA). A 62-year-old man, previously healthy, presented
      with 1-month ventilatory-independent right hemithorax back pain, dry cough and
      large effort dyspnea. He also referred weight loss of 12 kg in 10 months and
      denied hemoptysis. As antecedents, he smoked for 40 years and moderate daily
      alcoholism. On physical examination, the patient was in good general condition,
      hydrated and regular respiration at rest [blood pressure (BP) =120/80 mmHg; heart
      rate (HR) =90 bpm; respiratory rate (RR) =16 rpm]. Cardiac auscultation revealed
      two standard rhythmic sounds without murmurs. Pulmonary auscultation revealed a
      slightly diminished vesicular murmur in the lower 1/3 of the right hemithorax
      without adventitious noises. Chest radiography showed a mass over the right lower
      lung. A CT scan confirmed the radiography image with the mass extending along the
      right inferior pulmonary vein and a tumor in the LA. Transthoracic and
      transesophageal echocardiography revealed large mass within the LA (occupying
      almost the entire cavity), measuring about 10 cm * 3 cm at its largest diameter,
      prolapsing into the left ventricle. Bronchoscopy, head CT scan, and whole-body
      bone scintigraphy investigation did not show any distant metastasis. The patient
      was successfully operated removing the intracardiac and inferior pulmonary vein
      tumor with the aid of cardiopulmonary bypass, followed by a right inferior
      lobectomy carried out after 25 days. After 30 days from surgery presented
      seizures associated a brain metastasis evidenced by CT when adjuvant radio and
      chemotherapy was started. During the next 90 days, the clinical conditions
      worsened, and the patient died 4 months after the surgical treatment. The case
      report has two primary justifications, even considering the poor outcome: (I)
      rarity and (II) the possibility of the surgical treatment.

PMID- 29600104
TI  - Identifying interlobar fissure in a Craig grade 4 fissureless patient by near
      infrared thoracoscopy.
AB  - Traditionally, surgeons can only count on their naked eyes to identify the
      fissure in patients with incomplete fissures, which often cause surgical approach
      into the fissural parenchyma and may lead to postoperative prolonged air leak
      (PAL). We describe a novel technique using near-infrared (NIR) thoracoscopy with
      indocyanine green (ICG) to identify the fissure accurately and real-timely for
      the first time in a patient with totally fused oblique fissure (Craig grade 4).

PMID- 29600105
TI  - Fan-shaped ground-glass opacity (GGO) as a premonitory sign of pulmonary
      infarction: a case report.
AB  - Radiological findings of pulmonary infarction have been well characterized mainly
      in established infarction. However, the early course CT appearance of patients
      who develop pulmonary infarction has not yet been fully elucidated. A 50-year-old
      female with a history of postmenopausal hormone replacement therapy (HRT)
      presented with dry cough and high-resolution computed tomography (HRCT) findings
      of fan-shaped segmental ground-glass opacity (GGO) in the right lower lobe. As
      the parenchymal density in the GGO gradually enlarged over a period of 4 weeks in
      spite of antibiotic treatment, the patient was referred to our hospital on
      clinical suspicion of bronchioloalveolar cell carcinoma. However, the
      pathological findings of a transbronchial biopsy of the lesion were compatible
      with pulmonary infarction. After an endoscopic examination, the typical CT
      appearance of established pulmonary infarction was observed. Moreover, enhanced
      CT detected an intraluminal filling defect in the right lower lobe artery
      suggesting peripheral pulmonary emboli. Our case was a peripheral pulmonary
      infarction probably induced by HRT, and suggested that fan-shaped GGO may be a
      premonitory sign of pulmonary infarction.

PMID- 29600106
TI  - Systemic air embolism after computed tomography-guided hook wire localization:
      two case reports and literature review.
AB  - Computed tomography (CT)-guided hook wire localization is often used to identify
      small nodules prior to video-assisted thoracoscopic surgery (VATS). Pneumothorax,
      intrapulmonary hemorrhage, and wire dislodgement are well-known complications
      associated with the former procedure, but systemic air embolism (SAE) is an
      extremely rare and potentially fatal complication. We encountered two cases of
      SAE; one patient showed neurologic symptoms, whereas the other did not. With the
      patient in the supine position, 100% oxygen was inhaled via a face mask.
      Subsequently, symptoms were resolved, and we performed planned surgeries on that
      day. Operative and postoperative courses were uneventful, and both patients were
      discharged without any sequelae. In this case report, we describe our experience
      with the two patients and review related literature.

PMID- 29600107
TI  - Missed diagnosis of esophageal leiomyoma leading to esophagectomy: a case report
      and review of literatures.
AB  - Leiomyomas are the most common benign esophageal neoplasm. About half of them
      were smaller than 5 cm and asymptomatic with a stable size for many years.
      Esophageal leiomyomas that excess than 5 cm in size may develop as a consequence
      of giant one at rapid growth rate. This case report specifically describes a mid
      aged woman who experienced a missed diagnosis of an esophageal leiomyoma over
      three years, which was covered by mediastinal thymolipoma and it subsequently
      developed as a giant tumor occupying the entire esophagus that makes the simple
      enucleation impossible. A surgical intervention of esophagectomy had to be
      performed to manage this entity.

PMID- 29600108
TI  - Hydroxychloroquine-induced cardiomyopathy and heart failure in twins.
AB  - Hydroxychloroquine (HCQ)-induced cardiomyopathy is one of the rare but severe
      complications following prolonged HCQ use. However, the exact mechanism of HCQ
      cardiotoxicity remains unclear and it is difficult to identify risk factors. We
      present a case of twin sisters who both suffered from systemic lupus
      erythematosus (SLE) and HCQ-induced cardiomyopathy presenting with decompensated
      heart failure (HF), suggesting that genetic predisposition might be a factor in
      HCQ-induced cardiomyopathy.

PMID- 29600109
TI  - Two cases of "stone heart" with fatal outcome.
AB  - The "stone heart" syndrome is a rare but often fatal complication of cardiac
      surgery associated with hypertrophy of the myocardium. The mechanisms behind the
      syndrome are not fully understood. In this case report, we describe two cases of
      stone heart in newborn girls. Both girls were born with congenital heart
      abnormalities including ventricular septum defects (VSD), hypertrophy of the
      myocardium and patent arterial duct (PDA), which was prenatally diagnosed. In
      each of the two cases, the stone heart became evident immediately after
      initiating cardiopulmonary bypass, and ended fatally.

PMID- 29600110
TI  - CT angiography for coronary graft assessment.

PMID- 29600112
TI  - Determination of Phenolic Acids in Sugarcane Vinasse by HPLC with Pulse
      Amperometry.
AB  - A reversed-phase liquid chromatographic separation with pulsed amperometric
      detection of phenolic acids at a glassy carbon electrode is described.
      Chromatographic separation was carried out in isocratic conditions using 0.20
      mol.L-1 acetic acid (pH 5.0)/water (80 : 20, v/v) as mobile phase under constant
      working potential mode of 0.80 V. Chromatographic peaks presented high resolution
      and separation. Calibration curves exhibited excellent correlation coefficients,
      above 0.995. Linear ranges of the analytes, in mg L-1, were of 0.018-18 (gallic
      acid), 0.146-19 (vanillic acid), 0.13-17 (caffeic acid), 0.016-16 (ferulic acid),
      and 0.008-17 (p-coumaric acid), respectively. Limits of detection ranged from 1.6
      to 97 MUg.L-1 and precision varied in 1.73-3.78% interval. Concentrations of 19
      +/- 0.51 mg.L-1 and 7.8 +/- 2.5 mg.L-1 were found for vanillic and caffeic acids,
      respectively, in a sugarcane vinasse sample. Gallic, ferulic, and p-coumaric
      acids were not detected. Recovery results demonstrated that the proposed method
      is accurate, and it can be used to detect and quantify phenolic acids in
      sugarcane vinasse without any influence of interferents.

PMID- 29600113
TI  - Relationships between Translation and Transcription Processes during fMRI
      Connectivity Scanning and Coded Translation and Transcription in Writing Products
      after Scanning in Children with and without Transcription Disabilities.
AB  - Students with transcription disabilities (dysgraphia/impaired handwriting, n = 13
      or dyslexia/impaired word spelling, n = 16) or without transcription disabilities
      (controls) completed transcription and translation (idea generating, planning,
      and creating) writing tasks during fMRI connectivity scanning and compositions
      after scanning, which were coded for transcription and translation variables.
      Compositions in both groups showed diversity in genre beyond usual narrative
      expository distinction; groups differed in coded transcription but not
      translation variables. For the control group specific transcription or
      translation tasks during scanning correlated with corresponding coded
      transcription or translation skills in composition, but connectivity during
      scanning was not correlated with coded handwriting during composing in dysgraphia
      group and connectivity during translating was not correlated with any coded
      variable during composing in dyslexia group. Results are discussed in reference
      to the trend in neuroscience to use connectivity from relevant seed points while
      performing tasks and trends in education to recognize the generativity
      (creativity) of composing at both the genre and syntax levels.

PMID- 29600114
TI  - Participatory group prenatal education using photonovels: Evaluation of a lay
      health educator model with low-income Latinas.
AB  - Objective: The objective of this research was to examine the effectiveness of a
      participatory prenatal education program for low-income Latinas. Lay health
      educators facilitated groups using photonovels and experiential learning
      activities. Methods: We used a community-based participatory research approach
      with a mixed method evaluation. Data included participant pre- and post-test
      surveys, focus groups, and a medical record review of participant outcomes and a
      control-match group who received usual care. Results: Participants (n=43) showed
      a significant increase in their knowledge of pregnancy, childbirth, and
      breastfeeding (P < .001) and a significant increase in confidence at being able
      to navigate their pregnancies, care for themselves and their babies, and interact
      with health professionals (P <= .05). They reported an increase in social
      support, a deeper understanding of information from medical providers, greater
      engagement, and behavior changes. There were no statistically significant
      differences in health outcomes between the participants and the control group.
      Conclusions: This study demonstrated that 1) a participatory prenatal education
      program can be an effective way to foster health literacy and empowerment among
      low-income Latinas; and 2) trained lay educators can be effective group
      facilitators. The intervention's tripartite approach offers a vehicle for health
      professionals to partner with Latino communities to promote active participation
      and capacity building for health and change. This strategy could be adapted and
      tested with other topics and communities.

PMID- 29600115
TI  - The Elusive Nature of Truth in Scientific Studies and the Importance of Peer
      Review.

PMID- 29600116
TI  - Reducing Spatial Uncertainty Through Attentional Cueing Improves Contrast
      Sensitivity in Regions of the Visual Field With Glaucomatous Defects.
AB  - Purpose: Current clinical perimetric test paradigms present stimuli randomly to
      various locations across the visual field (VF), inherently introducing spatial
      uncertainty, which reduces contrast sensitivity. In the present study, we
      determined the extent to which spatial uncertainty affects contrast sensitivity
      in glaucoma patients by minimizing spatial uncertainty through attentional
      cueing. Methods: Six patients with open-angle glaucoma and six healthy subjects
      underwent laboratory-based psychophysical testing to measure contrast sensitivity
      at preselected locations at two eccentricities (9.5 degrees  and 17.5 degrees )
      with two stimulus sizes (Goldmann sizes III and V) under different cueing
      conditions: 1, 2, 4, or 8 points verbally cued. Method of Constant Stimuli and a
      single-interval forced-choice procedure were used to generate frequency of seeing
      (FOS) curves at locations with and without VF defects. Results: At locations with
      VF defects, cueing minimizes spatial uncertainty and improves sensitivity under
      all conditions. The effect of cueing was maximal when one point was cued, and
      rapidly diminished when more points were cued (no change to baseline with 8
      points cued). The slope of the FOS curve steepened with reduced spatial
      uncertainty. Locations with normal sensitivity in glaucomatous eyes had similar
      performance to that of healthy subjects. There was a systematic increase in
      uncertainty with the depth of VF loss. Conclusions: Sensitivity measurements
      across the VF are negatively affected by spatial uncertainty, which increases
      with greater VF loss. Minimizing uncertainty can improve sensitivity at locations
      of deficit. Translational Relevance: Current perimetric techniques introduce
      spatial uncertainty and may therefore underestimate sensitivity in regions of VF
      loss.

PMID- 29600117
TI  - Objective Evaluation of Visual Fatigue Using Binocular Fusion Maintenance.
AB  - Purpose: In this study, we investigated whether an individual's visual fatigue
      can be evaluated objectively and quantitatively from their ability to maintain
      binocular fusion. Methods: Binocular fusion maintenance (BFM) was measured using
      a custom-made binocular open-view Shack-Hartmann wavefront aberrometer equipped
      with liquid crystal shutters, wherein eye movements and wavefront aberrations
      were measured simultaneously. Transmittance in the liquid crystal shutter in
      front of the subject's nondominant eye was reduced linearly, and BFM was
      determined from the transmittance at the point when binocular fusion was broken
      and vergence eye movement was induced. In total, 40 healthy subjects underwent
      the BFM test and completed a questionnaire regarding subjective symptoms before
      and after a visual task lasting 30 minutes. Results: BFM was significantly
      reduced after the visual task (P < 0.001) and was negatively correlated with the
      total subjective eye symptom score (adjusted R2 = 0.752, P < 0.001). Furthermore,
      the diagnostic accuracy for visual fatigue was significantly higher in BFM than
      in the conventional test results (aggregated fusional vergence range, near point
      of convergence, and the high-frequency component of accommodative
      microfluctuations; P = 0.007). Conclusions: These results suggest that BFM can be
      used as an indicator for evaluating visual fatigue. Translational Relevance: BFM
      can be used to evaluate the visual fatigue caused by the new visual devices, such
      as head-mount display, objectively.

PMID- 29600118
TI  - Automated Method of Grading Vitreous Haze in Patients With Uveitis for Clinical
      Trials.
AB  - Purpose: Uveitis is associated with accumulation of exudate in the vitreous,
      which reduces fundus visibility. The condition is assessed in patients by
      subjectively matching fundus photographs to a six-level (NIH) or nine-level
      (Miami) haze scale. This study aimed to develop an objective method of assessing
      vitreous haze. Methods: An image-processing algorithm was designed that
      quantifies vitreous haze via high-pass filtering, entropy analysis, and power
      spectrum integration. The algorithm was refined using nine published photographs
      that represent incremental levels of fundus blur and applied without further
      refinement to 120 random fundus photographs from a uveitis image library.
      Computed scores were compared against the grades of two trained readers of
      vitreous haze and against acutance, a generic measure of image clarity, using
      Cohen's kappa and Gwet's AC statistics. Results: Exact agreement between
      algorithm scores and reader grades was substantial for both NIH and Miami scales
      (kappa = 0.61 and 0.67, AC = 0.82 and 0.92). Within-one (kappa = 0.78 and 0.82)
      and within-two (kappa = 0.80 and 0.84) levels of agreement were almost perfect.
      The correspondence was comparable to that between readers. Whereas, exact (kappa
      = 0.45 and 0.44, AC = 0.73 and 0.75), within-one (kappa = 0.69 and 0.68), and
      within-two (kappa = 0.73 and 0.72) levels of agreement for the two scales were
      moderate to substantial for acutance calculations. Conclusions: The computer
      algorithm produces a quantitative measure of vitreous haze that correlates
      strongly with the perception of expert graders. Translational Relevance: The work
      offers a rapid, unbiased, standardized means of assessing vitreous haze for
      clinical and telemedical monitoring of uveitis patients.

PMID- 29600119
TI  - A Rapid Extraction Method to Quantify Drug Uptake in Contact Lenses.
AB  - Purpose: To develop a simple extraction procedure to quantify the uptake of four
      topical ocular pharmaceutical drugs into contact lenses (CLs). Methods: Four
      silicone hydrogel (SH) CLs (balafilcon A, senofilcon A, lotrafilcon B, comfilcon
      B) and four conventional hydrogel (CH) CLs (nesofilcon A, hilafilcon B, nelfilcon
      A, etafilcon A) were evaluated. The drugs studied were natamycin, moxifloxacin,
      timolol maleate, and ketotifen fumarate. For drug incubation, three CLs of each
      type were placed in 1 mL of 1 mg/mL drug-loading solution for 24 hours. The
      lenses were then extracted in 2 mL methanol for 2 hours. This process was
      repeated to obtain a total of three extraction cycles. Detection of natamycin,
      moxifloxacin, ketotifen fumarate, and timolol maleate were measured by absorbance
      at 305, 287, 297, and 295 nm, respectively. Results: The majority of the drugs
      were extracted after the first extraction cycle (P < 0.001). For moxifloxacin and
      timolol, CH CLs had higher drug uptake than SH CLs (P < 0.05). There were no
      differences in drug uptake between CH CLs and SH CLs for natamycin and ketotifen
      (P > 0.05). Conclusions: This study provides a simple approach to determine drug
      uptake into CLs. This method can also be modified, such as changing the
      extraction time, extraction cycles, or extraction solvent to better suit other
      drugs and CL combinations. Translational Relevance: There is considerable
      interest in using CLs for ocular drug delivery. Accurately quantifying drug
      uptake on CLs has been a challenge. Hence, this study provides a simple method to
      quantify drug uptake in CLs.

PMID- 29600121
TI  - Reviewers.

PMID- 29600120
TI  - Towards Standardization of Quantitative Retinal Vascular Parameters: Comparison
      of SIVA and VAMPIRE Measurements in the Lothian Birth Cohort 1936.
AB  - Purpose: Semiautomated software applications derive quantitative retinal vascular
      parameters from fundus camera images. However, the extent of agreement between
      measurements from different applications is unclear. We evaluate the agreement
      between retinal measures from two software applications, the Singapore "I" Vessel
      Assessment (SIVA) and the Vessel Assessment and Measurement Platform for Images
      of the Retina (VAMPIRE), and examine respective associations between retinal and
      systemic outcomes. Method: Fundus camera images from 665 Lothian Birth Cohort
      1936 participants were analyzed with SIVA and VAMPIRE. Intraclass correlation
      coefficients (ICC) and Bland-Altman plots assessed agreement between retinal
      parameters: measurements of vessel width, fractal dimension, and tortuosity.
      Retinal-systemic variable associations were assessed with Pearson's correlation,
      and intersoftware correlation magnitude differences were examined with Williams's
      test. Results: ICC values indicated poor to limited agreement for all retinal
      parameters (0.159-0.410). Bland-Altman plots revealed proportional bias in the
      majority, and systematic bias in all measurements. SIVA and VAMPIRE measurements
      were associated most consistently with systemic variables relating to blood
      pressure (SIVA r's from -0.122 to -0.183; VAMPIRE r's from -0.078 to -0.177).
      Williams's tests indicated significant differences in the magnitude of
      association between retinal and systemic variables for 7 of 77 comparisons (P <
      0.05). Conclusions: Agreement between two common software applications was poor.
      Further studies are required to determine whether associations with systemic
      variables are software-dependent. Translational Relevance: Standardization of the
      measurement of retinal vascular parameters is warranted to ensure that they are
      reliable and application-independent. This would be an important step towards
      realizing the potential of the retina as a source of imaging-derived biomarkers
      that are clinically useful.

PMID- 29600122
TI  - Addition of a Short Course of Prednisolone to a Gluten-Free Diet vs. Gluten-Free
      Diet Alone in Recovery of Celiac Disease: A Pilot Randomized Controlled Trial.
AB  - Background A gluten-free diet (GFD) is the standard of care in the management of
      patients with celiac disease, but clinical and histological recovery are often
      delayed. In newly diagnosed patients, strict compliance to GFD is difficult to
      achieve; this is especially true in developing countries where gluten-free food
      is often difficult to obtain. Steroids, when used alone, can be effective in
      inducing recovery in patients with celiac disease. We performed a randomized
      controlled trial to study the effect of a short course of prednisolone combined
      with a GFD on the recovery of celiac disease. Materials and methods This study
      was a single-center, randomised, open-label trial. This investigation was done in
      a pediatric gastroenterology unit of a tertiary teaching hospital in north
      India.Twenty-eight newly diagnosed celiac disease patients were enrolled in the
      study. Prednisolone was given at 1 mg/kg for four weeks; duodenal biopsies and
      IgA anti-tissue transglutaminase (tTg) levels were assessed at eight weeks, six
      months, and 12 months from the start of the study. Outcome measures The primary
      outcome measures used to indicate clinical, histological, and immunological
      recovery of celiac disease were clinical improvement at eight weeks and the
      proportion of patients with improved histology by at least one grade and who were
      tissue transglutaminase (tTg) seronegative at eight weeks. The secondary measures
      were the proportion of patients showing normalization of histological features
      and the proportions of patients becoming seronegative at six months and one year
      of GFD. Results Patients were randomized into the GFD only (n = 14) or GFD with
      prednisolone (GFD+P) (n = 14) groups. No significant differences were detected in
      clinical recovery at eight weeks; none of the patients became seronegative at
      eight weeks, six months, or 12 months. The proportion of patients with
      improvement in histology by at least one grade was higher in the GFD+P group at
      eight weeks, and there was no difference in overall histological improvement at
      12 months after starting treatment. Conclusion The addition of a short course of
      prednisolone to a GFD does not affect clinical and serological recovery but might
      result in rapid histological recovery compared to a GFD alone in patients newly
      diagnosed with celiac disease.

PMID- 29600123
TI  - Association Between Baseline Blood Pressures, Heart Rates, and Vasovagal Syncope
      in Children and Adolescents.
AB  - BACKGROUND: Vasovagal syncope is the most common cause of syncope in children and
      adults, accounting for 50-66% of unexplained syncope. There are no studies
      establishing the relationship between syncope, baseline heart rate, and blood
      pressure. OBJECTIVE: To identify a possible association between baseline blood
      pressure and heart rate with syncope. DESIGN/METHODS: We conducted a
      questionnaire-based chart review study. A questionnaire was distributed to the
      guardian of children between eight and 18 years of age who attended the Pediatric
      Ambulatory Care Clinic at Flushing Hospital Medical Center. Based on the
      responses in the questionnaire, subjects were classified either as cases
      (positive for syncope) or controls (negative for syncope). Children and
      adolescents with neurological, cardiac, or any medical condition that can cause
      syncopal episodes were excluded from the study. Data collected from the
      questionnaire included age, gender, ethnicity, medical history, family history of
      syncope, and the amount of salt used in food. Anthropometric and vital signs for
      the current visit (height, weight, BMI, blood pressure, and heart rate) and vital
      signs from two previous visits were collected from electronic medical records.
      The data was analyzed using t-test and chi-square test with Microsoft Excel
      software (Microsoft Office Standard, v. 14, Microsoft; 2010); p<0.05 was
      considered significant. RESULTS: A total of 197 subjects were included in this
      study. There were 18 cases and 179 controls. Of the cases, (4/18) 22.2% were more
      likely to have a systolic blood pressure lower than the 10th percentile for their
      gender, age, and height as compared with controls (7/179) 3.9%, p = 0.003. The
      subjects with a history of syncope were more likely to add salt to their food (p
      = 0.004). There were no significant differences between cases and controls for
      age, gender, ethnicity between cases and controls for systolic blood pressure. No
      significant difference was observed between the heart rates of cases and
      controls. CONCLUSIONS: Children and adolescents with syncope were more likely to
      have a systolic blood pressure lower than the 10th percentile, and there was no
      difference in the baseline heart rate. In addition, children with syncope were
      more likely to add salt to their food.

PMID- 29600124
TI  - Palatal Injection does not Block the Superior Alveolar Nerve Trunks: Correcting
      an Error Regarding the Innervation of the Maxillary Teeth.
AB  - The superior alveolar nerves course lateral to the maxillary sinus and the
      greater palatine nerve travels through the hard palate. This difficult three
      dimensional anatomy has led some dentists and oral surgeons to a critical
      misunderstanding in developing the anterior and middle superior alveolar (AMSA)
      nerve block and the palatal approach anterior superior alveolar (P-ASA) nerve
      block. In this review, the anatomy of the posterior, middle and anterior superior
      alveolar nerves, greater palatine nerve, and nasopalatine nerve are revisited in
      order to clarify the anatomy of these blocks so that the perpetuated anatomical
      misunderstanding is rectified. We conclude that the AMSA and P-ASA nerve
      blockades, as currently described, are not based on accurate anatomy.

PMID- 29600125
TI  - Overtesting in Japan.

PMID- 29600126
TI  - Rehabilitation pharmacotherapy: A combination of rehabilitation and
      pharmacotherapy.
AB  - Sarcopenia, malnutrition, and polypharmacy are major causes of frailty in older
      people. Some frail older people become disabled through stroke, pneumonia, hip
      fracture, and other diseases. Sarcopenia, malnutrition, and polypharmacy tend to
      worsen disability in older people. Rehabilitation pharmacotherapy and
      rehabilitation nutrition are important to improve frailty and disability in older
      people under these circumstances.

PMID- 29600127
TI  - The diagnostic accuracy of the mediastinal width on supine anteroposterior chest
      radiographs with nontraumatic Stanford type A acute aortic dissection.
AB  - Background: Nontraumatic Stanford type A acute aortic dissection is a life
      threatening condition; thus, the ability to make a precise diagnosis of
      nontraumatic Stanford type A acute aortic dissection is essential for the
      emergency physician. Several reports have shown that the mediastinal widening on
      a chest radiograph is useful for the diagnosis of nontraumatic Stanford type A
      acute aortic dissection; however, the exact cutoff value of the mediastinal width
      on plain radiographs is rarely defined. Methods: A single-center retrospective
      case-control study was conducted between October 1, 2013, and March 31, 2015. We
      evaluated the maximal mediastinal width of the anteroposterior chest X-ray at the
      level of the aortic knob in the supine position between patient groups with and
      without nontraumatic Stanford type A acute aortic dissection. Results: We
      enrolled 72 patients (36 patients with nontraumatic Stanford type A acute aortic
      dissection and 36 patients without nontraumatic Stanford type A acute aortic
      dissection). The median mediastinal width of patients with nontraumatic Stanford
      type A acute aortic dissection was significantly larger than that of patients
      without nontraumatic Stanford type A acute aortic dissection (100.7 mm vs 77.7
      mm, P < .01). The optimal cutoff level was 87 mm (sensitivity, 81%; specificity,
      89%). Using multivariable logistic regression, the odds ratio of a mediastinal
      width of >87 mm for a diagnosis nontraumatic Stanford type A acute aortic
      dissection was 57.1 (95% confidence interval, 11.2-290.2). Conclusion: A
      mediastinal width of >87 mm showed high sensitivity in the diagnosis of probable
      nontraumatic Stanford type A acute aortic dissection.

PMID- 29600128
TI  - Fatal necrotizing myositis from fulminant Streptococcus dysgalactiae subspecies
      equisimilis (SDSE) infection: A case report of autopsy images.
AB  - Over the past few decades, Streptococcus dysgalactiae subspecies equisimilis
      (SDSE) have been considered as weak pathogenicity compared with S. pyogenes
      (GAS). Some recent reports argue that SDSE may bring severe soft tissue infection
      as same as GAS. No reports have been tried to reveal the clinical characteristics
      and autopsy images of fulminant SDSE infection. In this case report, we aimed to
      present a case of fatal necrotizing myositis from fulminant SDSE infection at
      iliopsoas, including autopsy appearance.

PMID- 29600129
TI  - Severe pleuritis and pericarditis associated with very-late-onset systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disorder, which occurs mostly
      in young women. However, late-onset SLE does exist and sometimes presents with an
      atypical, diversified course. We describe an 85-year-old woman who was admitted
      to our hospital for lower extremity edema and hand grip weakness. Chest computed
      tomography scan 4 days after admission demonstrated rapid accumulation of pleural
      and pericardial effusions, which did not exist on admission. She was diagnosed
      with pleuritis and pericarditis associated with very-late-onset SLE.
      Methylprednisolone pulse therapy resulted in a drastic improvement in serositis.
      Our case exemplifies the fact that patients with late-onset SLE sometimes follow
      an atypical course, which makes the clinical diagnosis difficult.

PMID- 29600130
TI  - Diagnosis of cystic fibrosis in an adult Japanese male.
AB  - Chest computed tomography image of a 23-year-old man. Image shows right-sided
      middle and lower lobe consolidation and multiple cystic bronchiectasis.

PMID- 29600131
TI  - Tick bite-Erythema migrans.
AB  - This manuscript describes the typical presentation of erythema migrans caused by
      tick bite. The purposes of this article are (i) to encourage physicians to
      observe patients with tick bite carefully since it may cause fatal encephalitis,
      and (ii) to facilitate physicians, especially in endemic areas, to consider tick
      borne encephalitis virus as one of the causes of encephalitis.

PMID- 29600132
TI  - Tetanus without apparent history of trauma.
AB  - A-68-year-old male was admitted due to tetanus without apparent history of
      trauma. Trismus was observed on admission and was improved after treatment.

PMID- 29600133
TI  - Anterior spinal cord syndrome-"owl's eye sign".
AB  - Magnetic resonance imaging revealing abnormally high signal intensity in the
      thoracic cord, extending from T5 to T10 on a sagittal T2-weighted image (Figure
      1A). An axial T2-weighted image showing "owl's eye sign" involving central
      anterior cord (Figure 1B), which was consistent with anterior spinal cord
      syndrome.

PMID- 29600134
TI  - Achenbach's syndrome in an elderly woman.
AB  - Achenbach's syndrome is a rare condition, but may be encountered in the primary
      care setting. The symptoms may be surprising to the patient and cause anxiety.

PMID- 29600135
TI  - Synthesis and characterization of two new TiO2-containing benzothiazole-based
      imine composites for organic device applications.
AB  - The effect of the presence of titanium dioxide in two new imines, (E,E)-(butane
      1,4-diyl)bis(oxybutane-4,1-diyl) bis(4-{[(benzo[d][1,3]thiazol-2
      yl)methylidene]amino}benzoate) (SP1) and (E)-N-[(benzo[d][1,3]thiazol-2
      yl)methylidene]-4-dodecylaniline (SP2), on the properties and stability of
      imine:TiO2 composites for organic device applications were examined. The
      investigated titanium dioxide (in anatase form, obtained via the sol-gel method)
      exhibited a surface area of 59.5 m2/g according to Brunauer-Emmett-Teller theory,
      and its structure is a combination of both meso- and microporous. The average
      pore diameter calculated by the Barrett-Joyner-Halenda method was 6.2 nm and the
      cumulative volume of pores was 0.117 m3/g. The imine SP1 exhibited columnar
      organization (Col), while SP2 revealed a hexagonal columnar crystalline phase
      (Colhk). The imine:TiO2 mixtures in various weight ratio (3:0, 3:1, 3:2, 3:3)
      showed a lower energy gap and HOMO-LUMO energy levels compared to pure TiO2. This
      implies that TiO2 provides not only a larger surface area for sensitizer
      adsorption and good electron collection, but also causes a shift of the imine
      energy levels resulting from intermolecular interaction. Also the temperature of
      the phase transition was slightly affected with the increase of TiO2
      concentration in imine-based composites. The changes observed in the Fourier
      transform middle-infrared absorption (FT-MIR) spectra confirmed the significant
      influence of TiO2 on structural properties of both investigated imines. Similar
      interactions of oxygen vacancies existing on the TiO2 surface with SP1 and SP2
      were observed. The imine:TiO2 mixtures showed good air stability and reusability,
      which demonstrates its potential for organic device applications.

PMID- 29600136
TI  - A review of carbon-based and non-carbon-based catalyst supports for the selective
      catalytic reduction of nitric oxide.
AB  - Various types of carbon-based and non-carbon-based catalyst supports for nitric
      oxide (NO) removal through selective catalytic reduction (SCR) with ammonia are
      examined in this review. A number of carbon-based materials, such as carbon
      nanotubes (CNTs), activated carbon (AC), and graphene (GR) and non-carbon-based
      materials, such as Zeolite Socony Mobil-5 (ZSM-5), TiO2, and Al2O3 supported
      materials, were identified as the most up-to-date and recently used catalysts for
      the removal of NO gas. The main focus of this review is the study of catalyst
      preparation methods, as this is highly correlated to the behaviour of NO removal.
      The general mechanisms involved in the system, the Langmuir-Hinshelwood or Eley
      Riedeal mechanism, are also discussed. Characterisation analysis affecting the
      surface and chemical structure of the catalyst is also detailed in this work.
      Finally, a few major conclusions are drawn and future directions for work on the
      advancement of the SCR-NH3 catalyst are suggested.

PMID- 29600137
TI  - Heavy-metal detectors based on modified ferrite nanoparticles.
AB  - In this work, we analyze artificial heavy-metal solutions with ferrite
      nanoparticles. Measurements of adsorption effectiveness of different kinds of
      particles, pure magnetite or magnetite doped with calcium, cobalt, manganese, or
      nickel ions, were carried out. A dependence of the adsorption efficiency on the
      composition of the inorganic core has been observed. Ferrites surfaces were
      modified by phthalic anhydride (PA), succinic anhydride (SA), acetic anhydride
      (AA), 3-phosphonopropionic acid (3-PPA), or 16-phosphohexadecanoic acid (16-PHDA)
      to compare the adsorption capability of the heavy metals Cd, Cu and Pb. The
      obtained nanoparticles were structurally characterized by transmission electron
      microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR) and Mossbauer spectroscopy. The amounts of Cd, Cu and Pb were
      measured out by atomic absorption spectroscopy (AAS) and energy dispersive X-ray
      (EDX) as comparative techniques. The performed study shows that SA linker appears
      to be the most effective in the adsorption of heavy metals. Moreover, regarding
      the influence of the composition of the inorganic core on the detection ability,
      the most effective ferrite Mn0.5Fe2.5O4 was selected for discussion. The highest
      heavy-metal adsorption capability and universality was observed for SA as a
      surface modifier.

PMID- 29600138
TI  - Surface-plasmon-enhanced ultraviolet emission of Au-decorated ZnO structures for
      gas sensing and photocatalytic devices.
AB  - Pure and Au-decorated sub-micrometer ZnO spheres were successfully grown on glass
      substrates by simple chemical bath deposition and photoreduction methods. The
      analysis of scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) images, energy-dispersive X-ray spectroscopy (EDS), UV-vis
      absorption, and photoluminescence (PL) spectra results were used to verify the
      incorporation of plasmonic Au nanoparticles (NPs) on the ZnO film. Time-resolved
      photoluminescence (TRPL) spectra indicated that a surface plasmonic effect exists
      with a fast rate of charge transfer from Au nanoparticles to the sub-micrometer
      ZnO sphere, which suggested the strong possibility of the use of the material for
      the design of efficient catalytic devices. The NO2 sensing ability of as
      deposited ZnO films was investigated with different gas concentrations at an
      optimized sensing temperature of 120  degrees C. Surface decoration of plasmonic
      Au nanoparticles provided an enhanced sensitivity (141 times) with improved
      response (tauRes = 9 s) and recovery time (tauRec = 39 s). The enhanced gas
      sensing performance and photocatalytic degradation processes are suggested to be
      attributed to not only the surface plasmon resonance effect, but also due to a
      Schottky barrier between plasmonic Au and ZnO structures.

PMID- 29600139
TI  - Valley-selective directional emission from a transition-metal dichalcogenide
      monolayer mediated by a plasmonic nanoantenna.
AB  - Background: Two-dimensional (2D) transition-metal dichalcogenides (TMDCs) with
      intrinsically crystal inversion-symmetry breaking have shown many advanced
      optical properties. In particular, the valley polarization in 2D TMDCs that can
      be addressed optically has inspired new physical phenomena and great potential
      applications in valleytronics. Results: Here, we propose a TMDC-nanoantenna
      system that could effectively enhance and direct emission from the two valleys in
      TMDCs into diametrically opposite directions. By mimicking the emission from each
      valley of the monolayer of WSe2 as a chiral point-dipole emitter, we demonstrate
      numerically that the emission from different valleys is directed into opposite
      directions when coupling to a double-bar plasmonic nanoantenna. The
      directionality derives from the interference between the dipole and quadrupole
      modes excited in the two bars, respectively. Thus, we could tune the emission
      direction from the proposed TMDC-nanoantenna system by tuning the pumping without
      changing the antenna structure. Furthermore, we discuss the general principles
      and the opportunities to improve the average performance of the nanoantenna
      structure. Conclusion: The scheme we propose here can potentially serve as an
      important component for valley-based applications, such as non-volatile
      information storage and processing.

PMID- 29600140
TI  - Facile synthesis of a ZnO-BiOI p-n nano-heterojunction with excellent visible
      light photocatalytic activity.
AB  - In this paper, an efficient method to produce a ZnO/BiOI nano-heterojunction is
      developed by a facile solution method followed by calcination. By tuning the
      ratio of Zn/Bi, the morphology varies from nanoplates, flowers to nanoparticles.
      The heterojunction formed between ZnO and BiOI decreases the recombination rate
      of photogenerated carriers and enhances the photocatalytic activity of ZnO/BiOI
      composites. The obtained ZnO/BiOI heterostructured nanocomposites exhibit a
      significant improvement in the photodegradation of rhodamine B under visible
      light (lambda >= 420 nm) irradiation as compared to single-phase ZnO and BiOI. A
      sample with a Zn/Bi ratio of 3:1 showed the highest photocatalytic activity
      (~99.3% after 100 min irradiation). The photodegradation tests indicated that the
      ZnO/BiOI heterostructured nanocomposites not only exhibit remarkably enhanced and
      sustainable photocatalytic activity, but also show good recyclability. The
      excellent photocatalytic activity could be attributed to the high separation
      efficiency of the photoinduced electron-hole pairs as well as the high specific
      area.

PMID- 29600141
TI  - Graphene composites with dental and biomedical applicability.
AB  - Pure graphene in the form of few-layer graphene (FLG) - 1 to 6 layers - is
      biocompatible and non-cytotoxic. This makes FLG an ideal material to incorporate
      into dental polymers to increase their strength and durability. It is well known
      that graphene has high mechanical strength and has been shown to enhance the
      mechanical, physical and chemical properties of biomaterials. However, for
      commercial applicability, methods to produce larger than lab-scale quantities of
      graphene are required. Here, we present a simple method to make large quantities
      of FLG starting with commercially available multi-layer graphene (MLG). This FLG
      material was then used to fabricate graphene dental-polymer composites. The
      resultant graphene-modified composites show that low concentrations of graphene
      (ca. 0.2 wt %) lead to enhanced performance improvement in physio-mechanical
      properties - the mean compressive strength increased by 27% and the mean
      compressive modulus increased by 22%. Herein we report a new, cheap and simple
      method to make large quantities of few-layer graphene which was then incorporated
      into a common dental polymer to fabricate graphene-composites which shows very
      promising mechanical properties.

PMID- 29600142
TI  - Effect of microtrichia on the interlocking mechanism in the Asian ladybeetle,
      Harmonia axyridis (Coleoptera: Coccinellidae).
AB  - The hindwings of beetles are folded under the elytra when they are at rest but
      are extended during flight, which can provide bioinspiration for the design of
      deployable micro air vehicles (MAVs). Beetle hindwings must be able to be both
      securely locked under the elytra and freely extended for flight, depending on the
      required action. To investigate the locking mechanism, this study used
      environmental scanning electron microscopy (ESEM) to examine the microstructures
      of the elytra, hindwings and abdomen of the Asian ladybeetle, Harmonia axyridis
      (Pallas, 1773). On the ventral side (VS) of the elytra, the microtrichia show a
      transitional structure from the lateral edge to the medial edge. On the hindwing
      surface, the folded regions were observed on both the dorsal side (DS) and the
      VS. On the abdomen, the microtrichia between the abdominal segments show a
      cyclical change from sparse to dense in each segment in the middle of the
      abdomen. Furthermore, the different directions of microtrichia that lead to self
      locking friction on the surfaces of the hindwing, elytron and abdomen appear to
      facilitate interlocking. A model for the interlocking of the hindwings of the H.
      axyridis was established, and its underlying mechanism is discussed.

PMID- 29600143
TI  - Effect of ferroelectric BaTiO3 particles on the threshold voltage of a smectic A
      liquid crystal.
AB  - The influence of small ferroelectric BaTiO3 particles on the planar-homeotropic
      transition threshold voltage in smectic A liquid crystals consisting of p
      nitrophenyl p-decyloxybenzoate and 4-cyano-4'-pentylbiphenyl were studied by
      using capacitance-voltage (C-V) measurements. It was shown that the BaTiO3
      particles significantly reduce the threshold voltage. The obtained result is
      explained by two factors: an increase of dielectric anisotropy of the liquid
      crystals and the formation of a strong electric field near polarized particles of
      BaTiO3. It was shown that the role of the second factor is dominant. The
      explanations of some features observed in the C-V characteristics are given.

PMID- 29600144
TI  - Noble metal-modified titania with visible-light activity for the decomposition of
      microorganisms.
AB  - Commercial titania photocatalysts were modified with silver and gold by
      photodeposition, and characterized by diffuse reflectance spectroscopy (DRS), X
      ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning
      transmission electron microscopy (STEM). It was found that silver co-existed in
      zero valent (core) and oxidized (shell) forms, whereas gold was mainly zero
      valent. The obtained noble metal-modified samples were examined with regard to
      antibacterial (Escherichia coli (E. coli)) and antifungal (Aspergillus niger (A.
      niger), Aspergillus melleus (A. melleus), Penicillium chrysogenum (P.
      chrysogenum), Candida albicans (C. albicans)) activity under visible-light
      irradiation and in the dark using disk diffusion, suspension, colony growth
      ("poisoned food") and sporulation methods. It was found that silver-modified
      titania, besides remarkably high antibacterial activity (inhibition of bacterial
      proliferation), could also decompose bacterial cells under visible-light
      irradiation, possibly due to an enhanced generation of reactive oxygen species
      and the intrinsic properties of silver. Gold-modified samples were almost
      inactive against bacteria in the dark, whereas significant bactericidal effect
      under visible-light irradiation suggested that the mechanism of bacteria
      inactivation was initiated by plasmonic excitation of titania by localized
      surface plasmon resonance of gold. The antifungal activity tests showed efficient
      suppression of mycelium growth by bare titania, and suppression of mycotoxin
      generation and sporulation by gold-modified titania. Although, the growth of
      fungi was hardly inhibited through disc diffusion (inhibition zones around
      discs), it indicates that gold does not penetrate into the media, and thus, a
      good stability of plasmonic photocatalysts has been confirmed. In summary, it was
      found that silver-modified titania showed superior antibacterial activity,
      whereas gold-modified samples were very active against fungi, suggesting that
      bimetallic photocatalysts containing both gold and silver should exhibit
      excellent antimicrobial properties.

PMID- 29600145
TI  - Towards the third dimension in direct electron beam writing of silver.
AB  - Carboxylates constitute an extremely promising class of precursor compounds for
      the electron beam induced deposition of silver. In this work both silver 2,2
      dimethylbutyrate and silver pentafluoropropionate were investigated with respect
      to their dwell-time-dependent deposition behavior and growth characteristics.
      While silver 2,2-dimethylbutyrate showed a strong depletion in the center of the
      impinging electron beam profile hindering any vertical growth, silver
      pentafluoropropionate indicated a pronounced dependency of the deposit height on
      the dwell time. Truly three-dimensional silver structures could be realized with
      silver pentafluoropropionate. The pillars were polycrystalline with silver
      contents of more than 50 atom % and exhibit strong Raman enhancement. This
      constitutes a promising route towards the direct electron beam writing of three
      dimensional plasmonic device parts from the gas phase.

PMID- 29600146
TI  - Perfusion double-channel micropipette probes for oxygen flux mapping with single
      cell resolution.
AB  - Measuring cellular respiration with single-cell spatial resolution is a
      significant challenge, even with modern tools and techniques. Here, a double
      channel micropipette is proposed and investigated as a probe to achieve this goal
      by sampling fluid near the point of interest. A finite element model (FEM) of
      this perfusion probe is validated by comparing simulation results with
      experimental results of hydrodynamically confined fluorescent molecule diffusion.
      The FEM is then used to investigate the dependence of the oxygen concentration
      variation and the measurement signal on system parameters, including the
      pipette's shape, perfusion velocity, position of the oxygen sensors within the
      pipette, and proximity of the pipette to the substrate. The work demonstrates
      that the use of perfusion double-barrel micropipette probes enables the detection
      of oxygen consumption signals with micrometer spatial resolution, while
      amplifying the signal, as compared to sensors without the perfusion system. In
      certain flow velocity ranges (depending on pipette geometry and configuration),
      the perfusion flow increases oxygen concentration gradients formed due to
      cellular oxygen consumption. An optimal perfusion velocity for respiratory
      measurements on single cells can be determined for different system parameters
      (e.g., proximity of the pipette to the substrate). The optimum perfusion
      velocities calculated in this paper range from 1.9 to 12.5 MUm/s. Finally, the
      FEM model is used to show that the spatial resolution of the probe may be varied
      by adjusting the pipette tip diameter, which may allow oxygen consumption mapping
      of cells within tissue, as well as individual cells at subcellular resolution.

PMID- 29600147
TI  - Comparative study of antibacterial properties of polystyrene films with TiO x and
      Cu nanoparticles fabricated using cluster beam technique.
AB  - Background: Antibacterial materials are of high importance for medicine, and for
      the production and conservation of food. Among these materials, polymer films
      with metal nanoparticles (NPs) are of considerable interest for many practical
      applications. Results: The paper describes a novel approach for the formation of
      bactericidal polymer thin films (polystyrene in this case), produced by spin
      coating, with Ti and Cu NPs deposited from cluster beams. Ti NPs are treated in
      three different ways in order to study different approaches for oxidation and,
      thus, efficiency in formation of the particles with semiconducting properties
      required for the catalytic formation of reactive oxygen species. Cu NPs are used
      as deposited. Partial NP embedding into polystyrene is realised in a controllable
      manner using thermal annealing in order to improve surface adhesion and make the
      particles resistant against wash-out. The formed composite films with TiO x and
      Cu species are tested as bactericidal media using E.coli bacteria as model
      microorganisms. Conclusion: The obtained results show considerable efficiency in
      destroying the bacteria and a good possibility of multiple re-use of the same
      composite films making the suggested approach attractive for the cases requiring
      reusable polymer-based antibacterial media.

PMID- 29600148
TI  - Optical orientation of nematic liquid crystal droplets via photoisomerization of
      an azodendrimer dopant.
AB  - Two sequential transformations of the orientational structure in nematic liquid
      crystal droplets containing a dendrimer additive (nanosized macromolecules with
      light-absorbing azobenzene terminal moieties) under light irradiation in the UV
      blue spectral range were investigated. The origin of these transitions is in the
      change of the boundary conditions due to photoisomerization of the dendrimer
      adsorbed onto the liquid crystal-glycerol interface. It was shown that the
      photoisomerization processes of dendrimer molecules in a liquid crystal are
      accompanied by a spatial rearrangement of their azobenzene moieties, which is the
      key point in the explanation of the observed effects.

PMID- 29600149
TI  - Facile chemical routes to mesoporous silver substrates for SERS analysis.
AB  - Mesoporous silver nanoparticles were easily synthesized through the bulk
      reduction of crystalline silver(I) oxide and used for the preparation of highly
      porous surface-enhanced Raman scattering (SERS)-active substrates. An analogous
      procedure was successfully performed for the production of mesoporous silver
      films by chemical reduction of oxidized silver films. The sponge-like silver
      blocks with high surface area and the in-situ-prepared mesoporous silver films
      are efficient as both analyte adsorbents and Raman signal enhancement mediators.
      The efficiency of silver reduction was characterized by X-ray diffraction and X
      ray photoelectron spectroscopy. The developed substrates were applied for SERS
      detection of rhodamine 6G (enhancement factor of about 1-5 * 105) and an anti
      ischemic mildronate drug (meldonium; enhancement factor of ~102) that is known
      for its ability to increase the endurance performance of athletes.

PMID- 29600150
TI  - Effect of annealing treatments on CeO2 grown on TiN and Si substrates by atomic
      layer deposition.
AB  - In this work, we investigate the effect of thermal treatment on CeO2 films
      fabricated by using atomic layer deposition (ALD) on titanium nitride (TiN) or on
      silicon (Si) substrates. In particular, we report on the structural, chemical and
      morphological properties of 25 nm thick ceria oxide with particular attention to
      the interface with the substrate. The annealing treatments have been performed in
      situ during the acquisition of X-Ray diffraction patterns to monitor the
      structural changes in the film. We find that ceria film is thermally stable up to
      annealing temperatures of 900  degrees C required for the complete
      crystallization. When ceria is deposited on TiN, the temperature has to be
      limited to 600  degrees C due to the thermal instability of the underlying TiN
      substrate with a broadening of the interface, while there are no changes detected
      inside the CeO2 films. As-deposited CeO2 films show a cubic fluorite
      polycrystalline structure with texturing. Further, after annealing at 900 
      degrees C an increase of grain dimensions and an enhanced preferential (200)
      orientation are evidenced. These findings are a strong indication that the
      texturing is an intrinsic property of the system more than a metastable condition
      due to the ALD deposition process. This result is interpreted in the light of the
      contributions of different energy components (surface energy and elastic modulus)
      which act dependently on the substrate properties, such as its nature and
      structure.

PMID- 29600151
TI  - Nanoscale mapping of dielectric properties based on surface adhesion force
      measurements.
AB  - The detection of local dielectric properties is of great importance in a wide
      variety of scientific studies and applications. Here, we report a novel method
      for the characterization of local dielectric distributions based on surface
      adhesion mapping by atomic force microscopy (AFM). The two-dimensional (2D)
      materials graphene oxide (GO), and partially reduced graphene oxide (RGO), which
      have similar thicknesses but large differences in their dielectric properties,
      were studied as model systems. Through direct imaging of the samples with a
      biased AFM tip in PeakForce Quantitative Nano-Mechanics (PF-QNM) mode, the local
      dielectric properties of GO and RGO were revealed by mapping their surface
      adhesion forces. Thus, GO and RGO could be conveniently differentiated. This
      method provides a simple and general approach for the fast characterization of
      the local dielectric properties of graphene-based materials and will further
      facilitate their applications in energy generation and storage devices.

PMID- 29600152
TI  - Bioinspired self-healing materials: lessons from nature.
AB  - Healing is an intrinsic ability in the incredibly biodiverse populations of the
      plant and animal kingdoms created through evolution. Plants and animals approach
      healing in similar ways but with unique pathways, such as damage containment in
      plants or clotting in animals. After analyzing the examples of healing and
      defense mechanisms found in living nature, eight prevalent mechanisms were
      identified: reversible muscle control, clotting, cellular response, layering,
      protective surfaces, vascular networks or capsules, exposure, and replenishable
      functional coatings. Then the relationship between these mechanisms, nature's
      best (evolutionary) methods of mitigating and healing damage, and existing
      technology in self-healing materials are described. The goals of this top-level
      overview are to provide a framework for relating the behavior seen in living
      nature to bioinspired materials, act as a resource to addressing the
      limitations/problems with existing materials, and open up new avenues of insight
      and research into self-healing materials.

PMID- 29600153
TI  - Cyclodextrin inhibits zinc corrosion by destabilizing point defect formation in
      the oxide layer.
AB  - Corrosion inhibitors are added in low concentrations to corrosive solutions for
      reducing the corrosion rate of a metallic material. Their mechanism of action is
      typically the blocking of free metal surface by adsorption, thus slowing down
      dissolution. This work uses electrochemical impedance spectroscopy to show the
      cyclic oligosaccharide beta-cyclodextrin (beta-CD) to inhibit corrosion of zinc
      in 0.1M chloride with an inhibition efficiency of up to 85%. Only a monomolecular
      adsorption layer of beta-CD is present on the surface of the oxide covered metal,
      with Raman spectra of the interface proving the adsorption of the intact beta-CD.
      Angular dependent X-ray photoelectron spectroscopy (ADXPS) and ultraviolet
      photoelectron spectroscopy (UPS) were used to extract a band-like diagram of the
      beta-CD/ZnO interface, showing a large energy level shift at the interface,
      closely resembling the energy level alignment in an n-p junction. The energy
      level shift is too large to permit further electron transfer through the layer,
      inhibiting corrosion. Adsorption hence changes the defect density in the
      protecting ZnO layer. This mechanism of corrosion inhibition shows that affecting
      the defect chemistry of passivating films by molecular inhibitors maybe a viable
      strategy to control corrosion of metals.

PMID- 29600154
TI  - Scanning speed phenomenon in contact-resonance atomic force microscopy.
AB  - This work presents data confirming the existence of a scan speed related
      phenomenon in contact-mode atomic force microscopy (AFM). Specifically, contact
      resonance spectroscopy is used to interrogate this phenomenon. Above a critical
      scan speed, a monotonic decrease in the recorded contact-resonance frequency is
      observed with increasing scan speed. Proper characterization and understanding of
      this phenomenon is necessary to conduct accurate quantitative imaging using
      contact-resonance AFM, and other contact-mode AFM techniques, at higher scan
      speeds. A squeeze film hydrodynamic theory is proposed to explain this
      phenomenon, and model predictions are compared against the experimental data.

PMID- 29600155
TI  - Correction: Computing the T-matrix of a scattering object with multiple plane
      wave illuminations.
AB  - [This corrects the article DOI: 10.3762/bjnano.8.66.].

PMID- 29600156
TI  - Comparative study of sculptured metallic thin films deposited by oblique angle
      deposition at different temperatures.
AB  - Metals with a wide range of melting points are deposited by electron beam
      evaporation under oblique deposition geometry on thermally oxidized Si
      substrates. During deposition the sample holder is cooled down to 77 K. It is
      observed that all obliquely deposited metals grow as tilted, high aspect ratio
      columns and hence with a similar morphology. A comparison of such columns with
      those deposited at room temperature (300 K) reveals that shadowing dominates the
      growth process for columns deposited at 77 K, while the impact of surface
      diffusion is significantly increased at elevated substrate temperatures.
      Furthermore, it is discussed how the incidence angle of the incoming particle
      flux and the substrate temperature affect the columnar tilt angles and the
      porosity of the sculptured thin films. Exemplarily for tilted Al columns
      deposited at 77 K and at 300 K, in-plane pole figure measurements are carried
      out. A tendency to form a biaxial texture as well as a change in the crystalline
      structure depending on the substrate temperature is found for those films.

PMID- 29600157
TI  - Electro-optical interfacial effects on a graphene/pi-conjugated organic
      semiconductor hybrid system.
AB  - The influence of graphene and retinoic acid (RA) - a pi-conjugated organic
      semiconductor - interface on their hybrid system is investigated. The physical
      properties of the interface are assessed via scanning probe microscopy, optical
      spectroscopy (photoluminescence and Raman) and ab initio calculations. The
      graphene/RA interaction induces the formation of a well-organized pi-conjugated
      self-assembled monolayer (SAM) at the interface. Such structural organization
      leads to the high optical emission efficiency of the RA SAM, even at room
      temperature. Additionally, photo-assisted electrical force microscopy, photo
      assisted scanning Kelvin probe microscopy and Raman spectroscopy indicate a RA
      induced graphene doping and photo-charge generation. Finally, the optical
      excitation of the RA monolayer generates surface potential changes on the hybrid
      system. In summary, interface-induced organized structures atop 2D materials may
      have an important impact on both design and operation of pi-conjugated
      nanomaterial-based hybrid systems.

PMID- 29600158
TI  - Toxicity and Applications of Internalised Magnetite Nanoparticles Within Live
      Paramecium caudatum Cells.
AB  - The nanotechnology revolution has allowed us to speculate on the possibility of
      hybridising nanoscale materials with live substrates, yet significant doubt still
      remains pertaining to the effects of nanomaterials on biological matter. In this
      investigation, we cultivate the ciliated protistic pond-dwelling microorganism
      Paramecium caudatum in the presence of excessive quantities of magnetite
      nanoparticles in order to deduce potential beneficial applications for this
      technique, as well as observe any deleterious effects on the organisms' health.
      Our findings indicate that this variety of nanoparticle is well-tolerated by P.
      caudatum cells, who were observed to consume them in quantities exceeding 5-12%
      of their body volume: cultivation in the presence of magnetite nanoparticles does
      not alter P. caudatum cell volume, swimming speed, growth rate or peak colony
      density and cultures may persist in nanoparticle-contaminated media for many
      weeks. We demonstrate that P. caudatum cells ingest starch-coated magnetite
      nanoparticles which facilitates their being magnetically immobilised whilst
      maintaining apparently normal ciliary dynamics, thus demonstrating that
      nanoparticle biohybridisation is a viable alternative to conventional forms of
      ciliate quieting. Ingested magnetite nanoparticle deposits appear to aggregate,
      suggesting that (a) the process of being internalised concentrates and may
      therefore detoxify (i.e. render less reactive) nanomaterial suspensions in
      aquatic environments, and (b) P. caudatum is a candidate organism for
      programmable nanomaterial manipulation and delivery.

PMID- 29600159
TI  - Immunosuppressant Peptide Abu-TGIRIS-Abu-NH2 and its Application for Treatment of
      Multiple Sclerosis.
AB  - Immunosuppressant peptide immunocortin for the first time was described in 1993.
      It corresponds to residues 11-20 of human Ig heavy chain (conserved motif of VH
      domain). There are no data about production of immunocortin by proteolysis of Ig
      in vivo. Synthetic immunocortin in concentration ~ 10-9 M suppresses phagocytosis
      in peritoneal macrophages, ConA-dependent blast transformation of rat
      lymphocytes, exhibits ACTH-like neurotropic activity and was suggested as a
      potential drug for treatment of a multiple sclerosis (MS). Here, we report a
      sequence and method of synthesis of Abu-TGIRIS-Abu-NH2 (Abu, alpha-aminobutyric
      acid), an artificial analogue of immunocortin. Biological trials of peritoneally
      injected Abu-TGIRIS-Abu-NH2 gave an evidence of its better efficacy versus
      immunocortin in a test for suppression of the experimental autoimmune
      encephalomyelitis (EAE) in Dark Agouti (DA) rats.

PMID- 29600161
TI  - Optimizing T Cell Expansion in a Hollow-Fiber Bioreactor.
AB  - Purpose of Review: Recent developments in regenerative medicine have precipitated
      the need to expand gene-modified human T cells to numbers that exceed the
      capacity of well-plate-based, and flask-based processes. This review discusses
      the changes in process development that are needed to meet the cell expansion
      requirements by utilizing hollow-fiber bioreactors. Maintenance of cell
      proliferation over long periods can become limited by unfilled demands for
      nutrients and oxygen and by the accumulation of waste products in the local
      environment. Recent Findings: Perfusion feeding, improved gas exchange, and the
      efficient removal of lactate can increase the yield of T cells from an average of
      10.8E +09 to more than 28E +09 in only 10 days. Summary: Aggressively feeding
      cells and actively keeping cells in the bioreactor improves gas exchange and
      metabolite management over semi-static methods. The ability to remove the
      environmental constraints that can limit cell expansion by using a two-chamber
      hollow-fiber bioreactor will be discussed.

PMID- 29600160
TI  - Multifaceted Roles of Connexin 43 in Stem Cell Niches.
AB  - Purpose of Review: Considerable progress has been made in the field of stem cell
      research; nonetheless, the use of stem cells for regenerative medicine therapies,
      for either endogenous tissue repair or cellular grafts post injury, remains a
      challenge. To better understand how to maintain stem cell potential in vivo and
      promote differentiation ex vivo, it is fundamentally important to elucidate the
      interactions between stem cells and their surrounding partners within their
      distinct niches. Recent Findings: Among the vast array of proteins depicted as
      mediators for cell-to-cell interactions, connexin-comprised gap junctions play
      pivotal roles in the regulation of stem cell fate both in vivo and in vitro.
      Summary: This review summarizes and illustrates the current knowledge regarding
      the multifaceted roles of Cx43, specifically, in various stem cell niches.

PMID- 29600162
TI  - Fetal Mesenchymal Stromal Cells: an Opportunity for Prenatal Cellular Therapy.
AB  - Purpose of Review: The aim of the study is to provide an overview on the
      possibility of treating congenital disorders prenatally with mesenchymal stromal
      cells (MSCs). Recent Findings: MSCs have multilineage potential and a low
      immunogenic profile and are immunomodulatory and more easy to expand in culture.
      Their ability to migrate, engraft and differentiate, or act via a paracrine
      effect on target tissues makes MSCs candidates for clinical therapies. Fetal and
      extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from
      adult sources. Summary: MSCs may be safely transplanted prenatally via ultrasound
      guided injection into the umbilical cord. Due to these characteristics, fetal
      MSCs are of great interest in the field of in utero stem cell transplantation for
      treatment of congenital disease.

PMID- 29600164
TI  - From discourse to practice: the circulation of norms, ideas and practices of
      migration management through the implementation of the mobility partnerships in
      Moldova and Georgia.
AB  - This research wishes to contribute to the understanding of the migration policy
      regime of the European Union (EU), by considering an analytical perspective that
      privileges the standpoint of the countries of its neighbourhood. As an entry
      point, we have focused our analysis on the Mobility Partnership, a policy
      instrument of soft power, representative of the emblematic network governance
      privileged by the EU in its current political framework, the Global Approach to
      Migration and Mobility (GAMM). Applying an "instrument approach", our research
      raises the question of the role played by the Mobility Partnership in the
      circulation of norms, ideas and practices related to the "good governance" of
      international migration, and whether these are internalized by the partner third
      countries. We present the results of a comparative analysis of two study-cases,
      Moldova and Georgia, countries considered by the European Commission as the "best
      pupils" in the implementation of their Mobility Partnerships, with the ambition
      to interrogate whether this instrument leads to a "common understanding" between
      the EU and the national actors that may lead to a translation of the European
      objectives in the field of migration into the registries of practices in the
      countries of the Eastern neighbourhood. Lastly, we will discuss the strategic
      "usage" of this instrument from the partner third countries, that can lead to
      different results, from complete absorption of the objectives, to resistance in
      their implementation.

PMID- 29600163
TI  - The Role of Steroid Hormones in Breast and Effects on Cancer Stem Cells.
AB  - Purpose of Review: This review will discuss how the steroid hormones, estrogen
      and progesterone, as well as treatments that target steroid receptors, can
      regulate cancer stem cell (CSC) activity. The CSC theory proposes a hierarchical
      organization in tumors where at its apex lies a subpopulation of cancer cells
      endowed with self-renewal and differentiation capacity. Recent Findings: In
      breast cancer (BC), CSCs have been suggested to play a key role in tumor
      maintenance, disease progression, and the formation of metastases. In preclinical
      models of BC, only a few CSCs are required sustain tumor re-growth, especially
      after conventional anti-endocrine treatments. CSCs include therapy-resistant
      clones that survive standard of care treatments like chemotherapy, irradiation,
      and hormonal therapy. Summary: The relevance of hormones for both normal mammary
      gland and BC development is well described, but it was only recently that the
      activities of hormones on CSCs have been investigated, opening new directions for
      future BC treatments and CSCs.

PMID- 29600165
TI  - miR-211 regulates the antioxidant function of lens epithelial cells affected by
      age-related cataracts.
AB  - AIM: To investigate the effects and mechanism of miR-211 in mediating the
      antioxidant function of lens epithelial cells affected by age-related cataracts.
      METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to
      detect miR-211 expression in the anterior lens capsules of healthy people, the
      anterior lens capsules of patients with age-related cataracts, and human
      epithelial cell line (SRA01/04) cells exposed to oxidative stress. A 2', 7'
      dichloro-fluorescein diacetate (DCFH-DA) probe was used to measure the levels of
      endogenous reactive oxygen species (ROS) in human lens epithelial cells (hLECs)
      exposed to 400 umol/L H2O2 for 1h. SRA01/04 cells were transfected with either
      miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls. After
      72h, these cells were exposed to 400 umol/L H2O2 for 1h, then p53 and Bax mRNA
      expression were measured using RT-qPCR. p53 and Bax protein expression were also
      measured by Western blotting analysis. Finally, cell viability was assessed using
      an MTS assay. RESULTS: Compared to the control group, expression of miR-211 in
      the anterior lens capsules of age-related cataract patients and in SRA01/04 cells
      exposed to oxidative stress was significantly increased (P<0.001). Levels of
      endogenous ROS were significantly elevated in hLECs exposed to oxidative stress
      (P<0.001). Compared to the mimic control group, the hLECs in the miR-211 mimic
      group expressed significantly higher levels of p53 and Bax mRNA and protein while
      cell viability was significantly reduced (P<0.001). Conversely, p53 and Bax mRNA
      and protein expression were significantly reduced in the miR-211 inhibitor group
      as compared to the control group, while the cells in this group had much higher
      levels of cell viability (P<0.001). CONCLUSION: miR-211 is upregulated in the
      anterior lens capsules of age-related cataract patients. miR-211 decreased the
      antioxidative stress capacity of lens epithelial cells by upregulating p53 and
      Bax, while inhibiting cell proliferation and repair. This finding suggests that
      miR-211 may play a key role in the development of age-related cataracts.

PMID- 29600166
TI  - Scleral ultrastructure and biomechanical changes in rabbits after negative lens
      application.
AB  - AIM: To address the microstructure and biomechanical changes of the sclera of
      rabbits after negative lens application by spectacle frame apparatus. METHODS:
      Five New Zealand rabbits of seven weeks post-natal were treated with -8 D lens
      monocularly over the course of two weeks. Refractive errors and axial length
      (AXL) were measured at the 1st, 7th and 14th days of the induction period.
      Ultrastructure of sclera was determined with electron microscopy. Biomechanical
      properties were tested by an Instron 5565 universal testing machine. RESULTS:
      Lens-induced (LI) eyes elongated more rapidly compared with fellow eyes with AXL
      values of 15.56+/-0.14 and 15.21+/-0.14 mm (P<0.01). Fibril diameter was
      significantly smaller in the LI eyes compared with control ones in the inner,
      middle, and outer layers (inner layer, 63.533 vs 76.467 nm; middle layer, 92.647
      vs 123.984 nm; outer layer, 86.999 vs 134.257 nm, P<0.01, respectively). In
      comparison with control eyes, macrophage-like cells that engulfed fibroblasts,
      dilated endoplasmic reticulum, and vacuoles in fibroblasts were observed in the
      inner and middle stroma in the LI eyes. Ultimate stress and Young's modulus were
      lower in the LI eyes compared with those in the control eyes. CONCLUSION:
      Negative lens application alters eye growth, and results in axial elongation with
      changes in scleral ultrastructural and mechanical properties.

PMID- 29600167
TI  - Protective effects of a composition of Chinese herbs-Gurigumu-13 on retinal
      ganglion cell apoptosis in DBA/2J glaucoma mouse model.
AB  - AIM: To explore the concrete mechanism of a Mongolian compound medicine-Gurigumu
      13 (GRGM) for glaucoma treatment. METHODS: DBA/2J mice, as glaucoma models, were
      intragastric administrated with GRGM to study the effect of GRGM on retinal
      ganglion cells (RGCs). The loss of RGCs was evaluated with the number of RGCs and
      axons. The expression of the target protein of RGCs or mouse retinas was
      determined by Western blot. The relative content of malondialdehyde (MDA) was
      examined by ELISA assay. RESULTS: GRGM distinctly improved retina damage via
      increasing the number of neurons, RGCs and axons in a concentration dependent
      manner. Meanwhile, GRGM obviously decreased the high level of MDA and the
      expression of oxidative stress-related proteins in retinas of DBA/2J mice, but
      promoted the expression of antioxidant proteins. Additionally, GRGM also
      significantly inhibited the protein expression of Bip and Chop, which were
      markers of endoplasmic reticulum stress-induced apoptosis. CONCLUSION: GRGM have
      obvious protective effects on RGCs in DBA/2J mice, and increase the number of
      RGCs and axons via inhibiting oxidative stress and endoplasmic reticulum stress.

PMID- 29600168
TI  - A recurrent G367R mutation in MYOC associated with juvenile open angle glaucoma
      in a large Chinese family.
AB  - AIM: To identify the mutations of MYOC, OPTN, CYP1B1 and WDR36 in a large Chinese
      family affected by juvenile open angle glaucoma (JOAG). METHODS: Of 114 members
      of one family were recruited in this study. Blood samples from twelve members of
      this pedigree were collected for further research. As a control, 100 unrelated
      subjects were recruited from the same hospital. The exon and flanking intron
      sequences of candidate genes were amplified using the polymerase chain reaction
      and direct DNA sequencing. RESULTS: The proband (III:10) was a seventy-three
      years old woman with binocular JOAG at the age of 31. A recurrent heterozygous
      mutation (c.1099G>A) of MYOC was identified in the three JOAG patients and
      another suspect. This transition was located in the first base pair of codon 367
      (GGA>AGA) in exon 3 of MYOC and was predicted to be a missense substitution of
      glycine to arginine (p.G367R) in myocilin. Mutations in OPTN, CYP1B1 or WDR36
      were not detected in this study. The G367R mutation was not present in unaffected
      family members or in 100 ethnically matched controls. Other variants of the
      coding regions of candidate genes were not detected in all participants. To date,
      this family was the largest to have been identified as carrying a certain MYOC
      mutation in China, further evidence of a founder effect for the G367R MYOC mutant
      was provided by our data. CONCLUSION: A MYOC c.1099G>A mutation in an autosomal
      dominant JOAG family is identified and the characteristic phenotypes among the
      patients are summarized. Genetic testing could be utilized in high-risk
      populations and be helpful not only for genetic counseling, but also for early
      diagnosis and treatment of affected patients or carriers of inherited JOAG.

PMID- 29600169
TI  - Mechanism of retinal pericyte migration through Angiopoietin/Tie-2 signaling
      pathway on diabetic rats.
AB  - AIM: To investigate the mechanism of pericyte migration through Angiopoietin-2
      (Ang-2)/Tie-2 signaling pathway. METHODS: We divided the rats into 5 groups. Each
      diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor,
      Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to
      examine the retinal vasculature including pericyte: endothelial ratio, and
      morphology of pericyte migration. Tie-2, ERK1/2 and Akt/PKB phosporylation were
      analyzed by confocal laser scanning microscopy. RESULTS: There was a correlation
      between pericyte migration with increasing Ang-2 (P<0.05). Pericyte number
      reduced by 40% (1:2.4) after 5wk diabetes on diabetic rats. The pericyte:
      endothelial ratio on group with Tie-2 inhibitor were 1:1.8. The same result shows
      on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results
      of pericyte: endothelial ratio (1:1.7). Inhibition on Tie-2 receptor decreased
      the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2
      inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on
      Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the
      same. CONCLUSION: Ang-2 has a role for pericyte migration on diabetic rats
      through Tie-2 receptor, ERK1/2 and Akt/PKB pathways. ERK1/2 is a dominant pathway
      based on the ability to supress another pathway activity and decreasing pericyte
      migration on diabetic rats.

PMID- 29600170
TI  - Is Marcus Gunn jaw winking a primitive reflex? Rat neuroanatomy.
AB  - AIM: To investigate a possible trigeminal proprioceptive-oculomotor neural
      pathway and explore possible synaptic connections between neurons in this
      pathway. Attempt to bring a new insight to mechanism of Marcus Gunn syndrome
      (MGS). METHODS: Anterograde and retrograde tract tracing was applied and combined
      with immunofluorescent stain in rats. After electrophysiological identifying
      mesencephalic trigeminal nucleus (Vme) neurons, intracellular injection of tracer
      was performed to trace axon trajectory. RESULTS: Following injections of
      anterograde tracers into the Vme, labeled terminals were observed ipsilateral in
      oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in
      interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with
      choline acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme
      projecting terminals contact upon ChAT positive III/IV motoneurons under confocal
      microscope. By retrograde labeling premotor neurons of the III, it showed that
      Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons
      in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to
      electric stimuli of the masseter nerve traveled into the ipsilateral III.
      CONCLUSION: There may exist a trigeminal proprioceptive-oculomotor system neural
      circuit in the rat, which is probably related to vertical-torsional eye
      movements. Possible association of this pathway with MGS etiology was discussed.

PMID- 29600171
TI  - Low concentration of sodium hyaluronate temporarily elevates the tear film lipid
      layer thickness in dry eye patients with lipid deficiency.
AB  - AIM: To investigate the effects of different concentrations of artificial tears
      on lipid layer thickness (LLT) and blink rate (BR) in dry eye patients. METHODS:
      This study included 106 eyes of 58 patients with dry eye. The lipid deficiency
      type was defined as the LLT baseline <75 nm. The LLT and BR were measured at
      baseline and 1, 5 and 15min after the instillation of 0.1% or 0.3% sodium
      hyaluronate (SH) eye drops by using the LipiView ocular surface interferometer.
      RESULTS: In the lipid deficiency group, the LLT increased from baseline at 1min
      post instillation. The LLT after the instillation of 0.1% SH was significantly
      higher than that after the instillation of 0.3% SH (P<0.001). The LLT returned to
      baseline at 15min post instillation of 0.1% SH and at 5min post instillation of
      0.3% SH. In the non-lipid deficiency group, the LLT decreased from baseline at
      1min and returned to baseline at 5min for both treatments. The BRs were not
      significantly different at different time points for both treatments. CONCLUSION:
      SH eye drops induce a short-term increase in LLT of patients with lipid
      deficiency. A low concentration of artificial tears have a stronger effect than a
      high concentration of artificial tears on the increase in LLT. In comparison, SH
      eye drops induce a transient and slight decrease in LLT of patients without lipid
      deficiency. A low concentration of artificial tears might be better for patients
      with lipid deficiency.

PMID- 29600172
TI  - Clinical outcome of combined conjunctival autograft transplantation and amniotic
      membrane transplantation in pterygium surgery.
AB  - AIM: To compare long-term outcome of primary and recurrent pterygium surgery with
      three different techniques: combined conjunctival autograft and overlay amniotic
      membrane transplantation (CAT with AMT), conjunctival autograft transplantation
      (CAT) alone and amniotic membrane transplantation (AMT) alone. METHODS: In this
      retrospective study, 142 eyes of 142 pterygium patients (104 primary, 38
      recurrent) who underwent CAT (group A), AMT (group B) or CAT with AMT (group C)
      respectively following surgical excision were reviewed and compared based on the
      recurrences and post-operative complications. RESULTS: The number of recurrence
      post-surgery were 17 (9 from primary, 8 from recurrent; the same description
      below), 18 (10, 8) and 2 (1, 1) in groups A, B, and C respectively; dry eyes were
      22 (16, 6), 27 (18, 9) and 7 (3, 4); conjunctival inflammations were 30 (17, 13),
      27 (16, 11) and 11 (6, 5). Patients in group C (either primary or recurrent or
      both) mainly showed significantly better results than those in group A or B
      (P<0.05) regarding above-mentioned clinical effects. CONCLUSION: Combined CAT and
      overly AMT have significantly lower rates of recurrence and postoperative
      complications for primary and recurrent pterygium surgery than CAT or AMT alone.

PMID- 29600173
TI  - Human lens epithelial cell apoptosis and epithelial to mesenchymal transition in
      femtosecond laser-assisted cataract surgery.
AB  - AIM: To evaluate human lens epithelium cell apoptosis and epithelial to
      mesenchymal transition (EMT) induced by femtosecond laser in femtosecond laser
      assisted cataract surgery (FLACS). METHODS: Sixty cataract patients with N2 to N3
      stage according to the LOCS III were enrolled in this study and divided into
      three groups randomly: FLACS1 group (cataract surgery by FLACS with LenSx),
      FLACS2 group (cataract surgery by FLACS with LensAR) and manual group (cataract
      surgery by phacoemulsification). Patients in two FLACS groups performed anterior
      capsulotomy by LenSx or LensAR laser system. Patients in the manual group were
      performed continuous curvilinear capsulorrhexis (CCC) manually. The anterior
      capsules were fixed right after moved out of eye. Hematoxylin-eosine staining,
      immunofluorescence staining and real-time PCR were performed in order to observe
      human lens epithelium cells changes after cataract surgery. RESULTS: The capsule
      cutting edge was shown irregularity and roughness in two FLACS groups and smooth
      edge in manual capsulotomy by pathologic staining. Irregularities of the cell
      configuration with partly swollen and destroyed nuclei were observed in two FLACS
      groups. Femtosecond laser could induce a significantly higher cell apoptosis in
      human lens epithelium cell than manually performed CCC (P<0.05). Lens epithelium
      cells apoptosis were correlated with femtosecond laser duration according to
      Pearson correlation analysis. Decreased N-cadherin expression, alpha-SMA and FSP
      1 level in two FLACS groups showed the inhibition of cell EMT. CONCLUSION:
      Femtosecond laser may affect the apoptosis and EMT of lens epithelium cells which
      are under the peeled central lens capsule.

PMID- 29600174
TI  - Outcomes of transconjunctival sutureless 27-gauge vitrectomy for vitreoretinal
      diseases.
AB  - AIM: To evaluate the safety and efficacy profile of 27-gauge (27G) pars plana
      vitrectomy (PPV) for the treatment of various vitreoretinal diseases. METHODS:
      The clinical outcomes of 61 eyes (58 patients) with various vitreoretinal
      diseases following 27G PPV were retrospectively reviewed. RESULTS: Surgical
      indications included rhegmatogenous retinal detachment (n=24), full-thickness
      macular hole (n=12), diabetic retinopathy (n=11), vitreous hemorrhage (n=6),
      Eales disease (n=4), pathological myopia-related vitreous floater (n=2), and
      macular epiretinal membrane (n=2). The mean follow-up was 166.4+/-61.3d (range 98
      339d). The mean logMAR best-corrected visual acuity (BCVA) improved from 1.7+/
      1.1 [0.02 decimal visual acuity (VA) equivalent] preoperatively to 1.2+/-1.0
      (0.06 decimal VA equivalent) at the last postoperative visit (P<0.001). The mean
      operative time was 49.9min. With the exception of complicated cataract in one
      eye, no intraoperative complications were encountered. No case required
      conversion to conventional 20-, 23- or 25G instrumentation in all surgical
      maneuvers except for silicone oil infusion, which required a 25G oil injection
      syringe. Postoperative complications included transient ocular hypertension,
      vitreous hemorrhage, persistent intraocular pressure elevation, subconjunctival
      oil leakage, and recurrent retinal detachment. No cases of hypotony,
      endophthalmitis, and sclerotomy-related tears were observed. CONCLUSION: The
      current results suggest that 27G PPV system is a safe and effective treatment for
      various vitreoretinal diseases. When learning to perform 27G PPV, surgeons may
      encounter a learning curve and should gradually expand surgical indications from
      easy to pathologically complicated cases.

PMID- 29600175
TI  - Long-term results of Ahmed glaucoma valve implantation in Egyptian population.
AB  - AIM: To evaluate the long-term results and complications of Ahmed glaucoma valve
      (AGV) implantation in a cohort of Egyptian patients. METHODS: A retrospective
      study of 124 eyes of 99 patients with refractory glaucoma who underwent AGV
      implantation and had a minimum follow-up of 5y was performed. All patients
      underwent complete ophthalmic examination and intraocular pressure (IOP)
      measurement before surgery and at 1d, weekly for the 1st month, 3, 6mo, and 1y
      after surgery and yearly afterward for 5y. IOP was measured by Goldmann
      applanation tonometry and/or Tono-Pen. Complications and the number of anti
      glaucoma medications needed were recorded. Success was defined as IOP less than
      21 mm Hg with or without anti-glaucoma medication and without additional glaucoma
      surgery. RESULTS: Mean age was 23.1+/-19.9y. All eyes had at least one prior
      glaucoma surgery. IOP was reduced from a mean of 37.2+/-6.8 to 19.2+/-5.2 mm Hg
      after 5y follow-up with a reduced number of medications from 2.64+/-0.59 to
      1.81+/-0.4. Complete and qualified success rates were 31.5% and 46.0%
      respectively at the end of follow-up. The most common complications were
      encapsulated cyst formation in 51 eyes (41.1%), complicated cataract in 9 eyes
      (7.25%), recessed tube in 8 eyes (6.45%), tube exposure in 6 eyes (4.8%) and
      corneal touch in 6 eyes (4.8%). Other complications included extruded AGV,
      endophthalmitis and persistent hypotony. Each of them was recorded in only 2 eyes
      (1.6%). CONCLUSION: Although refractory glaucoma is a difficult problem to
      manage, AGV is effective and relatively safe procedure in treating refractory
      glaucoma in Egyptian patients with long-term follow-up. Encapsulated cyst
      formation was the most common complication, which limits successful IOP control
      after AGV implantation. However, effective complications management can improve
      the rate of success.

PMID- 29600176
TI  - Automatic localization of macular area based on structure label transfer.
AB  - AIM: To explore feasibility and practicability of macula localization independent
      of macular morphological features. METHODS: A novel method was proposed to
      identify macula in fundus images by using structure label transfer. Its main idea
      was to match a processed image with the candidate images with known structures,
      and then transfer the structure label representing the macular to the processed
      image as a result of macula localization. In this way, macula localization
      couldn't be influenced by lesion or other interference any more. RESULTS: The
      average success rate in four datasets was 98.18%. For accuracy, the average error
      distance in four datasets was 0.151 optic disc diameter (ODD). Even for severe
      lesion images, the proposed method can still maintain high success rate and high
      accuracy, e.g., 95.65% and 0.124 ODD in the case of STARE dataset, respectively,
      which indicated that the proposed method was highly robust and stable in the
      complicated situations. CONCLUSION: The proposed method can avoid the
      interference of lesion to macular morphological features in macula localization,
      and can locate macula with high accuracy and robustness, verifying its
      feasibility.

PMID- 29600177
TI  - Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation
      combination therapy for macular edema secondary to retinal vein occlusion:
      preliminary report.
AB  - AIM: To evaluate the efficacy and safety of combined anti-vascular endothelial
      growth factor (VEGF) agents, oral glucocorticoid, and laser photocoagulation
      therapy for macular edema (ME) secondary to retinal vein occlusion (RVO).
      METHODS: This study included 16 eyes of 16 patients with RVO-associated ME.
      Patients were initially treated with oral prednisone and an intravitreal anti
      VEGF agent. Two weeks later, patients underwent standard laser photocoagulation.
      Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and retinal
      vessel oxygenation were examined over 12mo. RESULTS: Patients received 1.43+/
      0.81 anti-VEGF injections. Mean baseline and 12-month logMAR BCVA were 0.96+/
      0.51 (20/178) and 0.31+/-0.88 (20/40), respectively, in eyes with central retinal
      vein occlusion (CRVO) (P<0.00), and 1.02+/-0.45 (20/209) and 0.60+/-0.49 (20/80),
      respectively, in eyes with branch retinal vein occlusion (BRVO) (P<0.00). At
      12mo, CRT had significantly decreased in eyes with CRVO (P<0.00) and BRVO
      (P<0.00). Venous oxygen saturation had significantly increased in eyes with CRVO
      (P<0.00) and BRVO (P<0.00). No examined parameters were significantly different
      between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION: Anti
      VEGF, glucocorticoid, and photocoagulation combination therapy improves visual
      outcome, prolongs therapeutic effect, and reduces the number of intravitreal
      injections in eyes with RVO-associated ME.

PMID- 29600178
TI  - The optic nerve head perfusion and its correlation with the macular blood
      perfusion in unilateral idiopathic macular hole: an optical coherence tomography
      angiography study.
AB  - AIM: To compare the optic nerve head (ONH) perfusion in both eyes of unilateral
      idiopathic macular hole (IMH) with normal control group by using optical
      coherence tomography angiography (OCTA) and investigate its correlationship with
      the macular blood perfusion. METHODS: We performed a prospective and cross
      sectional study that included 19 patients with full-thickness unilateral IMH and
      24 age- and sex-matched controls. All participants received OCTA test. The ONH
      perfusion was evaluated by the regions of peripapillary and whole en face (the
      sum of peripapillary and optic disc). The potential correlationship between ONH
      and parafovea were implied. All the data were performed using the nonparametric
      test. RESULTS: The mean values of ONH presented that normal control >IMH
      >unaffected eyes. A statistical variation was found between three groups in the
      region of temporal (P=0.007). Vessel density notablely decreased on the layers of
      superficial, deep and choroid of parafovea region in IMH group. The correlative
      coefficients showed that respectively whole en face and deep retina: r=0.528,
      peripapillary and deep retina: r=0.525, whole en face and choriocapillaries:
      r=0.569, peripapillary and choriocapillaries: r=0.504. CONCLUSION: Our study
      demonstrate a reduced ONH vessel density in both eyes of IMH patients and the
      vessel density of ONH in IMH eyes are positively correlated with both the retina
      capillary and choriocapillary in parafoveal. The reduction of vessel densities
      may indicate the hypoperfusion in IMH eyes.

PMID- 29600179
TI  - Safety and efficacy of posterior sub-Tenon's carboplatin injection versus
      intravitreal melphalan therapy in the management of retinoblastoma with secondary
      vitreous seeds.
AB  - AIM: To evaluate the safety and efficacy of posterior sub-Tenon's carboplatin
      injection compared to intravitreal melphalan injection in the management of
      retinoblastoma (RB) with secondary vitreous seeds. The outcome measures were
      vitreous seeds regression, need for other treatment modalities to achieve ocular
      salvage and treatment side effects. METHODS: A prospective interventional
      comparative nonrandomized study included RB eyes developed secondary vitreous
      seeds during the period of follow up. They subdivided into two groups: study
      group I where posterior sub-Tenon's carboplatin (20 mg/2 mL) was injected and
      study group II where intravitreal melphalan (20 ug /0.1 mL) was injected. The
      injections repeated every 2-4wk. RESULTS: Thirty-three eyes were included in the
      study. Seventeen eyes (16 patients) in study group I and 16 eyes (16 patients) in
      study group II. Ten eyes (30.3%) were completely salvaged following local
      chemotherapies. Ocular salvage was 23.5% following posterior sub-Tenon's
      carboplatin injection versus 37.5% following intravitreal melphalan raised to
      47.1% and 75% with addition of external beam radiotherapy (EBR) with no
      statistically significant difference between the study groups (P=0.16). A
      statistically significant correlation was found between ocular salvage rate and
      type of vitreous seeds either dust, spheres and clouds (r=0.42, P=0.015) and eyes
      harbor new solid tumor growth (r=0.35, P=0.045). The mean and median follow up
      periods following local chemotherapy injections were 2.0y in the study group I
      and 2.37y in the study group II. Few complications were reported: periorbital
      edema in all eyes and ocular motility disturbances in 13 eyes (76.5%) following
      posterior sub-Tenon's carboplatin injection. Vitreous hemorrhage developed in 2
      eyes (12.5%) and localized retinopathy in 5 eyes (31.25%) following intravitreal
      melphalan. CONCLUSION: Local chemotherapy for treatment of RB with secondary
      vitreous seeds is safe and can salvage 30.3% of eyes without EBR. There is a
      superiority of intravitreal melphalan in ocular salvage however, no statistically
      significant difference between both groups.

PMID- 29600180
TI  - Cap morphology after small-incision lenticule extraction and its effects on
      intraocular scattering.
AB  - AIM: To investigate cap morphology after small-incision lenticule extraction
      (SMILE) and its effects on intraocular scattering. METHODS: Sixty-five eyes of 33
      patients undergoing SMILE were enrolled. In addition to regular evaluation,
      Fourier-domain optical coherence tomography was used to investigate cap thickness
      at 1d, 1wk, 1 and 3mo postoperatively. The optical quality including modulation
      transfer function cutoff frequency, Strehl ratio, Optical Quality Analysis System
      (OQAS) values, and objective scattering index (OSI), were evaluated using OQASTM.
      RESULTS: Cap thickness decreased from 1d to 1wk (P<0.001), but remained higher
      than intended thickness of 120 um after 3mo (P<0.001). Cap thickness in central
      area was thinner than that of in the paracentral and peripheral areas (P<0.0001).
      Total number of microdistortions decreased from 1d to 3mo (P<0.0001). Pearson
      analysis revealed a weak correlation between OSI and standard deviation of cap
      thickness at 1d and 1mo, as well as between range of cap thickness and OSI at
      1mo. No correlation was found between microdistortion and OSI, but a negative
      correlation existed between microdistortion and range at 1d and 1moafter surgery.
      CONCLUSION: The corneal cap tends to be more accurate and regular with time
      lapse. Better cap morphology tends to contribute less intraocular scattering in
      the eyes undergoing SMILE.

PMID- 29600181
TI  - Visual quality assessment after presbyopic laser in-situ keratomileusis.
AB  - AIM: To assess visual quality after presbyopia correction using an aspheric
      ablation profile and a micro-monovision protocol. METHODS: This is a
      retrospective interventional study. Fifty-four eyes of 27 patients (mean age,
      50.2+/-7.5y) who underwent presbyopia correction with an aspheric micro
      monovision protocol were enrolled. The values of modulation transfer function
      (MTF) cutoff frequency, Strehl ratio, objective scattering index (OSI) and
      accommodation range were quantitatively assessed using the HD analyzer.
      Preoperative and postoperative contrast sensitivity (CS) at far (2.5 m) and near
      (40 cm) distance and higher-order aberrations (HOAs) were analyzed. Subjective
      visual satisfaction was evaluated by self-reported questionnaire regarding
      optical visual symptoms. RESULTS: One year after presbyopia correction, no
      significant differences were found in the MTF cutoff frequency, Strehl ratio and
      OSI, however, the HD analyzer accommodation range significantly differed
      postoperatively (P=0.004). Postoperative CS at 12 and 18 cpd at near showed
      statistically significant improvement (P=0.020 and 0.008, respectively). Visual
      performance by self-reported questionnaire revealed satisfactory results in terms
      of subjective visual quality improvement. CONCLUSION: Objective optical quality
      parameters show good visual outcomes. Subjective visual quality assessed by self
      reported questionnaire in the presbyopia correction group show satisfactory
      results.

PMID- 29600182
TI  - Three-year results of small incision lenticule extraction and wavefront-guided
      femtosecond laser-assisted laser in situ keratomileusis for correction of high
      myopia and myopic astigmatism.
AB  - AIM: To compare and calculate the 3-year refractive results, higher-order
      aberrations (HOAs), contrast sensitivity (CS) and dry eye parameters after small
      incision lenticule extraction (SMILE) and wavefront-guided femtosecond laser
      assisted laser in situ keratomileusis (FS-LASIK) for correction of high myopia
      and myopic astigmatism. METHODS: In this prospective, non-randomized comparative
      study, 78 eyes with spherical equivalent (SE) of -8.11+/-1.09 diopters (D)
      received a SMILE surgery, and 65 eyes with SE of -8.05+/-1.12 D received a
      wavefront-guided FS-LASIK surgery with the VisuMax femtosecond laser (Carl Zeiss
      Meditec, Jena, Germany) for flap cutting. Visual acuity, manifest refraction, CS,
      HOAs, ocular surface disease index (OSDI) and tear break-up time (TBUT) were
      evaluated during a 3-year follow-up. RESULTS: The difference of uncorrected
      distance visual acuity (UDVA) postoperatively was achieved at 1mo and at 3mo,
      whereas the difference of the mean UDVA between two groups at 3y were not
      statistically significant (t=-1.59, P=0.13). The postoperative change of SE was
      0.89 D in the FS-LASIK group (t=5.76, P=0.00), and 0.14 D in the SMILE group
      (t=0.54, P=0.59) from 1mo to 3y after surgery. At 3-year postoperatively, both
      HOAs and spherical aberrations in the SMILE group were obviously less than those
      in the FS-LASIK group (P=0.00), but the coma root mean square (RMS) was higher in
      the SMILE group (0.59+/-0.26) than in the FS-LASIK group (0.29+/-0.14, P=0.00).
      The mesopic CS values between two groups were not statistically significant at 3y
      postoperatively. Compared with the FS-LASIK group, lower OSDI scores and longer
      TBUT values were found in the SMILE group at 1mo and 3mo postoperatively. With
      regard to safety, no eye lost any line of CDVA in both groups at 3y after
      surgery. CONCLUSION: Both SMILE and wavefront-guided FS-LASIK procedures provide
      good visual outcomes. Both procedures are effective and safe, but SMILE surgery
      achieve more stable long-term refractive outcome and better control of early
      postoperative dry eye as compared to FS-LASIK.

PMID- 29600183
TI  - The relationship between abduction deficit and reoperation among patients with
      infantile esotropia.
AB  - AIM: To determine the relationship between abduction deficit and reoperation
      among patients with infantile esotropia (IET). METHODS: The records of 216
      patients (432 eyes) with IET who underwent surgery, from 2010 to 2015 were
      studied. Patients with IET whose deviation appeared before 6mo of age and had
      stable preoperative deviation in two examinations with at least 2wk apart and a
      minimum 3mo postoperative follow up were included. Cases with early onset
      accommodative esotropia, congenital cataract, retinopathy of prematurity (ROP),
      manifest nystagmus, fundus lesions, neurologic and ophthalmic anomalies, 6th
      nerve palsy and Duane's syndrome were excluded. Preoperative abduction deficit
      was considered from -1 to -3 grading scale. Three months after surgery, children
      were classified into no-need reoperation [deviation<=15 prism diopters (PD)], and
      need-reoperation groups (deviation>15 PD). RESULTS: In this retrospective study,
      117 female and 99 male patients with the mean surgical age of 4.7+/-6.4y were
      included. Reoperation rate was 33.3% and 16.0% in IET patients with and without
      abduction deficit, respectively in patients who had a history of late surgery.
      Abduction deficit increased the odds of reoperation by 82% [OR=1.82, 95%
      confidence interval (CI) =1.05 to 3.19, P=0.003] in patients who had a history of
      late surgery (>2 years old, P=0.021). Abduction deficit was improved
      significantly after operation (P<0.001). CONCLUSION: Based on our results,
      abduction deficit can be considered as a risk factor of reoperation in IET
      patients who are operated at the age of more than 2y.

PMID- 29600184
TI  - Comparison of visual outcomes with implantation of trifocal versus bifocal
      intraocular lens after phacoemulsification: a Meta-analysis.
AB  - AIM: To compare a trifocal intraocular lens (IOL) and a bifocal IOL implantation
      in improving visual function after cataract surgery. METHODS: Eligible
      literatures were systematically searched through EMBASE and PubMed databases. The
      inclusion criteria were prospective comparative clinical trials on cataract
      surgery comparing trifocal IOL with bifocal IOL implantation that assessed visual
      acuity, contrast sensitivity and subjective vision quality. The effects were
      computed as standardized mean differences and pooled using fixed-effect or random
      effect models. RESULTS: Four prospective randomized controlled trials (RCTs) and
      five cohorts provided data were included by a systematic review, comprising 265
      eyes implanted with trifocal IOLs and 264 eyes implanted with bifocal IOLs.
      Monocular distance visual acuity (VA) showed a statistically significant but
      small difference that favored trifocal IOLs (MD=-0.06; 95%CI, -0.10 to -0.02;
      Z=2.90, P=0.004 for uncorrected distance VA, and MD= -0.02; 95%CI, -0.03 to 
      0.00; Z=2.02, P=0.04 for corrected distance VA), but the data did not suggest
      that the effect of trifocal IOL implantation would clinically outperform bifocal
      IOL implantation. There was no significant difference in monocular near VA (MD=
      0.01; 95%CI, -0.07 to 0.04; Z=0.42, P=0.68 for distance-corrected near VA, and
      MD=-0.01; 95%CI, -0.06 to 0.03; Z=0.55, P=0.58 for corrected near VA) or
      refraction between two groups. Contrast sensitivity and subjective visual quality
      had no conclusive results. CONCLUSION: All results indicate that trifocal IOL and
      bifocal IOL had similar levels of monocular distance and near VA.

PMID- 29600185
TI  - The relationship between insulin resistance/beta-cell dysfunction and diabetic
      retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng
      Diabetic Eye Study.
AB  - AIM: To investigate the relationship between insulin resistance (IR)/beta-cell
      dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2
      diabetes mellitus (T2DM), and to explore further whether there were differences
      in the relationship among diabetic patients with higher and lower body mass index
      (BMI). METHODS: Cross-sectional study. A total of 1466 subjects with T2DM were
      recruited in a local Desheng Community of urban Beijing from November 2009 to
      June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized
      evaluation was carried out for each participant, including questionnaire, ocular
      and anthropometric examinations, and laboratory tests. Seven fields 30 degrees 
      color fundus photographs were used for DR grading according to the Early
      Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment
      (HOMA) method was employed for IR and beta-cell function assessment. RESULTS:
      After excluding those participants who were treated with insulin (n=352) or had
      missing data of fasting insulin (n=96), and further excluding those with poor
      quality of retinal photographs (n=10), a total of 1008 subjects were included for
      the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging
      from 34 to 86 (64.87+/-8.28)y. Any DR (levels 14 and above) was present in 278
      (27.6%) subjects. After adjusting for possible covariates, the presence of any DR
      did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval
      (CI) 0.87-2.61, P=0.14] or HOMA beta-cell (OR 0.71, 95%CI 0.40-1.26, P=0.25).
      After stratification by BMI, the presence of any DR was associated positively
      with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P=0.016), and negatively with HOMA beta
      cell (OR 0.40, 95%CI: 0.19-0.87, P=0.021) in the group of patients with higher
      BMI (>=25 kg/m2). In the group of patients with lower BMI (<25 kg/m2), the
      presence of any DR was not associated with HOMA IR (OR 1.00, 95%CI: 0.43-2.33,
      P=1.00) or HOMA beta-cell (OR 1.41, 95%CI: 0.60-3.32, P=0.43). CONCLUSION: The
      data suggest that higher IR and lower beta-cell function are associated with the
      presence of DR in the subgroup of diabetic patients with higher BMI. However,
      this association is not statistically significant in diabetic patients with lower
      BMI.

PMID- 29600186
TI  - Symptomatic accommodative and binocular dysfunctions from the use of flat-panel
      displays.
AB  - AIM: To determine the presence of symptomatic accommodative and non-strabismic
      binocular dysfunctions (ANSBD) in a non-presbyopic population of video display
      unit (VDU) users with flat-panel displays. METHODS: One hundred and one VDU
      users, aged between 20 to 34y, initially participated in the study. This study
      excluded contact-lens wearers and subjects who had undergone refractive surgery
      or had any systemic or ocular disease. First, subjects were asked about the type
      and nature of eye symptoms they experienced during VDU use. Then, a thorough eye
      examination excluded those subjects with a significant uncorrected refractive
      error or other problem, such as ocular motility disorders, vertical deviation,
      strabismus and eye diseases. Finally, the remaining participants underwent an
      exhaustive assessment of their accommodative and binocular vision status.
      RESULTS: Eighty-nine VDU users (46 females and 43 males) were included in this
      study. They used flat-panel displays for an average of 5+/-1.9h a day. Twenty
      subjects presented ANSBD (22.5%). Convergence excess was the most frequent non
      strabismic binocular dysfunction (9 subjects), followed by fusional vergence
      dysfunction (3 subjects) and convergence insufficiency (2 subjects). Within the
      accommodative dysfunctions, accommodative excess was the most common (4
      subjects), followed by accommodative insufficiency (2 subjects). Moderate to
      severe eye symptoms were found in 13 subjects with ANSBD. CONCLUSION: Significant
      eye symptoms in VDU users with accommodative and/or non-strabismic binocular
      dysfunctions often occur and should not be underestimated; therefore, an
      appropriate evaluation of accommodative and binocular vision status is more
      important for this population.

PMID- 29600187
TI  - Endoscopy-assisted vitrectomy in the anterior vitreous.
AB  - Endoscopy-assisted ocular surgery is a relatively old technique that is
      increasingly being recognized for its application in cases of vitreoretinal
      disease. This technique is especially useful when both the vitreous and retina
      are difficult to access because of media opacity, a small pupil, or a
      microcornea. In this context, the anterior vitreous is often difficult to dissect
      because of its complex pathological changes. This article reviews the common
      anatomical features and pathologies that are observed in the anterior vitreous,
      as well as the applications and indications of endoscopy-assisted vitrectomy in
      the anterior vitreous.

PMID- 29600188
TI  - Lamellar keratoplasty with corneoscleral graft for limbal dermoids.
AB  - To assess the postoperative outcomes of limbal dermoid excision with
      corneoscleral graft transplantation. The charts of 8 consecutive patients (mean
      age: 13.0y) who had undergone limbal dermoid excision with lamellar corneoscleral
      graft transplantation by a single surgeon were retrospectively reviewed. Mean
      dermoid size was 7.75 mm (6.0-12.0 mm). Mean visual acuities (in logMAR units)
      before and after surgery were 1.8 and 1.7, respectively (P=0.29). Spherical
      equivalents were 1.3 diopter (D) before surgery and 0.7 D after surgery (P=0.40).
      The mean astigmatism measurements before and after surgery were 2.4 D and 1.5 D,
      respectively (P=0.17). Vector analysis revealed a mild change in astigmatism with
      a mean "d" of 3.2 (0.56-6.89). No intra- or post-operative complications
      occurred. Lamellar keratoplasty for limbal dermoids is safe and offers good
      cosmesis and tectonic stability. A significant decrease in the amount of
      astigmatism is not expected following surgery.

PMID- 29600189
TI  - A comparison of surgical efficacy between a 1.8-mm microincision and 3.2-mm and
      5.5-mm incisions for phacoemulsification.
AB  - Phacoemulsification is a commonly used surgical method in cataract surgery. This
      paper observes and compares the surgical efficacy of three incisions of different
      length for phacoemulsification to identify the optimal method for cataract
      surgery. Ninety patients were enrolled in the present study and divided into
      three groups. The 1.8-mm group received Bausch & Lomb MI60 foldable intraocular
      lens (IOL) implantation (n=30), 3.2-mm group received Bausch & Lomb Akreos AO
      foldable lens implantation (n=30), and 5.5-mm group received Alcon TYPE 05 rigid
      IOL implantation (n=30). Visual acuity, Oculyzer-based anterior segment analysis,
      and corneal endothelial cell count before surgery, and 3, 7, 30, and 90d after
      surgery were recorded and compared. Pseudophakic accommodation three days, one
      week, one month, and three months after surgery was determined. Intraoperative
      ultrasound time and ultrasonic energy were recorded. It was finally concluded
      that for phacoemulsification with the same phaco tip, a 1.8-mm microincision can
      lead to quicker recovery of visual acuity, more stable astigmatism, and higher
      pseudophakic accommodation than conventional incision.

PMID- 29600190
TI  - Toxocara optic neuropathy: clinical features and ocular findings.
AB  - We evaluated thirteen eyes of twelve patients diagnosed clinically and
      serologically with Toxocara optic neuropathy. Eleven patients had unilateral
      involvement and one patient had bilateral optic neuropathy. Eight patients
      (66.7%) had a possible infection source to Toxocara. Six patients (50%) had
      painless acute optic neuropathy. Ten eyes had asymmetric, sectorial optic disc
      edema with peripapillary infiltration and three eyes had diffuse optic disc
      edema. Eosinophilia was noted in five patients (41.7%) and optic nerve
      enhancement was observed in eight of eleven eyes (72.7%) with available orbit
      magnetic resonance imaging (MRI). Mean visual acuity significantly improved
      following treatment [mean logarithmic of the minimum angle of resolution (logMAR)
      0.94+/-0.56 at baseline and 0.47+/-0.59 at the final (P=0.02)]. Asymmetric optic
      disc edema with a peripapillary lesion and a history of raw meat ingestion were
      important clues for diagnosing Toxocara optic neuropathy. Additionally, Toxocara
      IgG enzyme-linked immunosorbent assay (ELISA) test and evaluating eosinophil may
      be helpful for diagnosis.

PMID- 29600191
TI  - Late onset acute Vogt-Koyanagi-Harada syndrome-challenges on the way.

PMID- 29600192
TI  - Choroidal vascular occlusion in a young male patient with sickle cell trait.

PMID- 29600193
TI  - Extracting intraocular foreign body at or near the ciliary body with scleral
      indentation in direct visualization.

PMID- 29600194
TI  - Function of Tumor Suppressors in Resistance to Antiandrogen Therapy and Luminal
      Epithelial Plasticity of Aggressive Variant Neuroendocrine Prostate Cancers.
AB  - Combined loss of tumor suppressors (TSPs), PTEN, TP53, and RB1, is highly
      associated with small cell carcinoma of prostate phenotype. Recent genomic
      studies of human tumors as well as analyses in mouse genetic models have revealed
      a unique role for these TSPs in dictating epithelial lineage plasticity-a
      phenomenon that plays a critical role in the development of aggressive variant
      prostate cancer (PCa) and associated androgen therapy resistance. Here, we
      summarize recently published key observations on this topic and hypothesize a
      possible mechanism by which concurrent loss of TSPs could potentially regulate
      the PCa disease phenotype.

PMID- 29600195
TI  - Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in
      Pathogenic Leptospira.
AB  - Leptospirosis is an emerging zoonotic disease with more than 1 million cases
      annually. Currently there is lack of evidence for signaling pathways involved
      during the infection process of Leptospira. In our comprehensive genomic analysis
      of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System
      (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain
      resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding
      genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon
      and are predicted to encode a hybrid histidine kinase and a hybrid response
      regulator, respectively. Transcriptome analysis of lvr mutant strains with
      disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional
      regulation of 850 differentially expressed genes. Phosphotransfer assays
      demonstrated that LvrA phosphorylates LvrB and predicted further signaling
      downstream to one or more DNA-binding response regulators, suggesting that it is
      a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved
      independently within different ecological lineages in Leptospira via gene
      duplication. This study uncovers a novel-signaling pathway that regulates
      virulence in pathogenic Leptospira (Lvr), providing a framework to understand the
      molecular bases of regulation in this life-threatening bacterium.

PMID- 29600196
TI  - Vibrio vulnificus RtxA1 Toxin Expression Upon Contact With Host Cells Is RpoS
      Dependent.
AB  - The expression of virulence genes in bacteria is known to be regulated by various
      environmental and host factors. Vibrio vulnificus, an estuarine bacterium,
      experiences a dramatic environmental change during its infection process. We
      reported that V. vulnificus RtxA1 toxin caused acute cell death only when close
      contact to host cells was allowed. A sigma factor RpoS is a very important
      regulator for the maximal survival of pathogens under stress conditions. Here, we
      studied the role of RpoS in V. vulnificus cytotoxicity and mouse lethality. The
      growth of rpoS mutant strain was comparable to that of wild-type in heart
      infusion (HI) media and DMEM with HeLa cell lysate. An rpoS mutation resulted in
      decreased cytotoxicity, which was restored by in trans complementation.
      Interestingly, host contact increased the expression and secretion of V.
      vulnificus RtxA1 toxin, which was decreased and delayed by the rpoS mutation.
      Transcription of the cytotoxic gene rtxA1 and its transporter rtxB1 was
      significantly increased after host factor contact, whereas the activity was
      decreased by the rpoS mutation. In contrast, the rpoS mutation showed no effect
      on the transcriptional activity of a cytolytic heamolysin gene (vvhA).
      Additionally, the LD50 of the rpoS mutant was 15-fold higher than that of the
      wild-type in specific pathogen-free CD-1 female mice. Taken together, these
      results show that RpoS regulates the expression of V. vulnificus RtxA1 toxin and
      its transporter upon host contact.

PMID- 29600198
TI  - Evidence-based medicine: why there is a low acceptance in countries like India?

PMID- 29600199
TI  - Radial Artery Pseudoaneurysm in a Post-operative Case of Midshaft Radius
      Fracture.
AB  - Introduction: Pseudoaneurysms of arteries are not uncommon complications of
      vessel handling during surgery. Early identification and management is important
      to prevent disastrous complications such as rupture and thrombosis. Case Report:
      We describe a case of a 28-year-old male who developed a pseudoaneurysm of the
      radial artery after being operated by plating for a mid-shaft radius fracture. He
      presented 2 weeks after surgery with swelling over the forearm which was
      confirmed to be a pseudoaneurysm after computed tomography angiography. It was
      treated with surgical excision and end-to-end anastomosis. Conclusion: A high
      index of suspicion must be maintained about the occurrence of this complication
      secondary to both trauma and surgery.

PMID- 29600197
TI  - Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction
      via Macrophage Recruitment.
AB  - Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human
      population, infects the enteric nervous system (ENS) in humans and rodents and
      causes intestinal neuromuscular dysfunction in rats. Although infiltration of
      inflammatory cells in the myenteric plexus and neurodegeneration of enteric
      nerves are common features of patients suffering from functional intestinal
      disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly
      because the underlying mechanisms are largely unknown. In this study we
      demonstrated that following intragastrical administration HSV-1 infects neurons
      within the myenteric plexus resulting in functional and structural alterations of
      the ENS. By infecting mice with HSV-1 replication-defective strain we revealed
      that gastrointestinal neuromuscular anomalies were however independent of viral
      replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced
      monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages
      in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced
      reactive oxygen and nitrogen species and directly harmed enteric neurons
      resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal
      neuromuscular dysfunctions were ameliorated by in vivo administration of (i)
      liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete
      tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the
      CCL2/CCR2 pathway, (iii) Nomega-Nitro-L-arginine methyl ester hydrochloride (L
      NAME) and AR-C 102222 to quench production of nitrogen reactive species produced
      via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric
      neurons recruit macrophages via production of a specific chemoattractant factor.
      The resulting inflammatory reaction is mandatory for intestinal dysmotility.
      These findings provide insights into the neuro-immune communication that occurs
      in the ENS following HSV-1 infection and allow recognition of an original
      pathophysiologic mechanism underlying gastrointestinal diseases as well as
      identification of novel therapeutic targets.

PMID- 29600200
TI  - Primary Lymphoma of the Pelvis: A Case Report.
AB  - Introduction: Primary lymphoma of the bone (PLB) is uncommon clinical entity with
      the vast majority of the cases are non-Hodgkin's lymphoma. Diffuse large B-cell
      lymphoma (DLBCL) is the most common subtype of PLB. Case Report: We report a case
      of 60-year-old female presented with pain in the right hip that persisted for 2
      months. Plain X-ray, computed tomography, and magnetic resonance imaging of the
      right hip showed a lytic lesion involving the right acetabulum and adjoining
      iliac bone with extraosseous mass. The histopathological and immunohistochemical
      examination confirmed a diagnosis of DLBCL. Treatment with cyclophosphamide,
      epirubicin, vincristine, and prednisone plus rituximabestablished a complete
      response (CR) with remodeling of the acetabulum. At the last follow-up, the
      patient had the ability to walk without any support which obviates the need of
      primary surgical interference for the tumor. Conclusion: The PLB must be
      considered in the differential diagnosis of lytic lesions involving the pelvic
      bones in older adults, especially when accompanied by extraosseous soft tissue
      mass. Our patient of PLB showed goodremodeling of the acetabular area after CR to
      chemotherapy without primary surgical interference for the tumor with the
      limitation of weight-bearing during chemotherapy treatment to prevent fracture.

PMID- 29600201
TI  - Femoral Head Stress Fracture in Children: A Case Report.
AB  - Introduction: The stress fracture of the femoral head rarely occurs; but, it is
      generally encountered in case of bone insufficiency, and it is exceptional in
      younger individuals. The main differential diagnosis may include several
      diseases, namely, slipped upper femoral epiphysis, septic arthritis,
      osteomyelitis, and Perthes' disease. Bone scintigraphy is very sensitive but
      lacks specificity. Nowadays, the magnetic resonance imaging (MRI) is the gold
      standard for an accurate diagnosis. Case Report: We present the first description
      of this pathology in the pediatric population with the particularity of its
      atypical aspect on MRI through a case of stress fracture of femoral head in 12
      year-old female. Conclusion: Stress fractures may sometimes mimic malignant or
      infectious lesions and are easily misdiagnosed. MRI is the gold standard which
      may be the only modality to identify the fracture.

PMID- 29600202
TI  - Late and Vague Presentation of Septic Arthritis of Hip in a IVDrug Abuser.
AB  - Introduction: Septic arthritis of the hip is a rare entity in acute presentation
      of hip pain in adults. Even though hip is the second most commonly affected
      joint, adult patients with septic arthritis not related to a surgical procedure
      represent <0.00001% of total acute admissions. Case Report: We present a 32-year
      old female intravenous drug abuser, positive for Hepatitis B and C who had
      started to inject her femoral veins 2 years ago. She presented with a 10 weeks
      history of radiating pain in the leg which was full, constant and diffuse in
      nature with hip stiffness. She was treated for sciatica by her GP. She had later
      visited A and E twice (5 and 8 weeks) and was again treated symptomatically. She
      started to have increasing pain, hip stiffness, reduced mobility, and developed
      swelling of both legs extending upto groin medially. The patient was apyrexial
      throughout these visits. She did not have back/buttock pain. X-ray showed loss of
      joint space with evidence of articular surface destruction. Ultrasound showed no
      fluid collection inside the joint and deep vein thrombosis was ruled out. Hip
      joint was aspirated, and cultures grew Staphylococcus aureus from the aspirate.
      Flucloxacillin and fucidin were started as per hospital protocol. Skin traction
      was applied for pain relief with active hip movements as possible. Magnetic
      resonance imaging demonstrated complete joint destruction post- infective septic
      arthritis. After 8 weeks of antibiotics, inflammatory markers improved. Follow up
      X-ray showed complete ankylosis of hip joint, severe restriction ofhip movements
      and was allowed weight bearing as possible. Conclusion: Risk of septic arthritis
      should always be considered in mind when dealing with these cohorts of patients.
      Threshold for septic arthritis should be much lower especially in patients with
      complicated history, current or ex-drug abuser and presenting with vague
      symptoms. Early diagnosis, detection of organisms, specific targeted antibiotics,
      and joint wash out with a future consideration of total hip arthroplasty when the
      infection has settled will help patients resume their normal function.

PMID- 29600203
TI  - Isolated Spontaneous Atraumatic Avulsion of Lesser Trochanter of Femur-A
      Pathognomonic Sign of Malignancy in Adults? A Case Report and Review of
      Literature.
AB  - Introduction: Avulsion fractures of lesser trochanter (LT) of femur are generally
      seen following trauma with intertrochanteric or sub trochanteric fractures. Non
      traumatic fractures of LT could oc-cur due to sudden violent contraction of the
      iliopsoas muscle that inserts on the LT; during vigorous exercise, or sudden pull
      involving flexion of hip. These are seen commonly in adolescents where the physis
      has not fused yet. Such a scenario in an adult patient most often or not leads to
      a diagnosis of an underlying malignancy or metastatic lesion. Case Report: A 60
      year-old female patient, presented to the outpatient department of our institute
      with pain on walking, with no history of trauma. X-ray showed an incidental
      finding of avulsion of LT of femur. Magnetic resonance imaging showed a large
      intramedullary tumour in the metaphysis though she had no symptoms or signs of
      malignancy. On further evaluation, she was diagnosed with primary lung carcinoma
      with widespread metastasis. Biopsy from the proximal femur also revealed a
      metastatic lesion. She was given palliative treatment in the form of a proximal
      femoral nail after which she was started on chemoradiation. Conclusion: A high
      index of suspicion of malignancy should be maintained in atraumatic fracture of
      LT in adults until proved otherwise. Lesser trochanter fracture.

PMID- 29600204
TI  - Acetabular Fracture after Hip Hemiarthroplasty: One Stage Procedure to a Total
      Hip Arthroplasty after Stabilization of the Fracture by Means of Cerclage Wires.
AB  - Introduction: Hip fractures in the elderly pose an increasing problem in society.
      In the elderly, a bipolar hemiarthroplasty (HA) remains the treatment of choice
      in case of hip fractures related to osteoporosis. However, due to an ongoing
      osteoporosis in this age group, a periprosthetic femoral fracture and a fracture
      of the unresurfaced acetabulum are increasingly noticed.In the literature, no
      information can be found regarding the treatment options for this kind of
      periprosthetic acetabular fracture. Case Report: We present a case report of a
      patient suffering an acetabular fracture 6 years after a HA. A one stage surgical
      procedure was the treatment of choice, consisting of a stabilization the
      acetabulum fracture by means of cerclage wires and a conversion of the HA to a
      total hip arthroplasty (THA). 4 months after surgery, she regained her pre
      operative functional status, and a radiographic evaluation of the right
      hemipelvis showed good signs ofthe fracture healing without migration ofthe
      acetabular component. Conclusion: This case shows a "one stage" surgery solution
      for an acetabular fracture after HA. Stabilization of the acetabulum fracture by
      means of cerclage wires and a conversion ofthe HA to a THAis a viable solution
      for this rare and challenging problem.

PMID- 29600205
TI  - Open Reduction and Internal Fixation of Posterior Fracture Dislocation of the
      Shoulder Made Easy!
AB  - Introduction: Posteriorly dislocated humeral head fracture has a great
      implication, as it is associated with high risk of avascular necrosis, limited
      access through the deltopectoral approach, and posterior approach to the
      posteriorly dislocated humeral fracture increases the risk to the remaining blood
      supply. Technical Tip: Posteriorly dislocated humeral fracture is approached
      through deltopectoral approach. Schanz pin is inserted into the humeral head to
      achieve purchase in the humeral head. Applying laterally directed force the
      humeral head is disengaged from the lateral margin of glenoid. A rotatory force
      then repositions the humeral head into a congruous position. Open reduction
      internal fixation is then carried out in a standard fashion. Conclusion:
      Retrieving the humeral head from the posteriorly dislocated position in patients
      with posterior fracture dislocation of the shoulder can be challenge to a trauma
      surgeon. With this novel technique, humeral head is reduced through deltopectoral
      approach without increasing the risk to the remaining blood supply.

PMID- 29600206
TI  - A Unique Case of Cervical Myelopathy in an Adult Patient with Scheie Syndrome.
AB  - Introduction: Scheie syndrome is an extremely rare systematic disease that
      represents the most attenuated form of mucopolysaccharidosis Type I disorder.
      Although associated with a variety of manifestations, Scheie syndrome leading to
      the development of cervical myelopathyis yet to be reported. Our purpose was to
      present a unique case of a Scheie syndrome patient, who underwent surgery due to
      cervical myelopathy, and to discuss the clinical and imaging findings, as well as
      the challenges and outcomes of surgical treatment. Case Report: A 33-year-old man
      with Scheie syndrome presented with neck and radicular pain, upper extremity
      weakness, and insecure gait. The workup studies revealedcervical spine stenosis
      at multiple levels, caused by accumulation of soft tissue, within the cervical
      spinal canal. D espite the high risks of anesthesia, and the patient's inherent
      poor bone quality that could lead to failure of spinal fusion, we decided to
      proceed with surgery; indeed, decompressive laminectomies combined with C1-7
      posterior stabilization led to immediate pain relief. Despite counter advised,
      the patient returned to sports rather early, and 6months after index procedure
      neck pain relapsed, while screw breakage and cutout occurred at the level of C7.
      Consequently, the initial instrumentation was revised and extended at T2 level.
      At 2years follow-up, the patient remained continuously pain-free and ambulatory.
      Conclusion: Although cervical myelopathy in Scheie syndrome represents an
      extremely rare entity, it can make a severe impact on patients' quality of life.
      If timely managed though, these patients can be offered a significant relief from
      symptoms. Surgery is rather challenging and treating physicians should be aware
      of the high risks of anesthesia. Especially spine surgeons should be aware of the
      nature of the disease, since it may not allow for fusion, causing instrumentation
      to fail.

PMID- 29600207
TI  - Treating a Recalcitrant Non-union of the Radius Using Autogenous Bone, Equine
      Bone Paste, Equine Demineralized Bone Matrix, Platelet Rich Plasma, and Bone
      Marrow Aspirate. A Case Report.
AB  - Introduction: Non-unions at forearms are usually challenging and difficult to
      treat. If additionally, an infection is present, reconstructive surgery should be
      planned only after full debridement, antibiotic treatment, and confirmation,
      based on clinical observation and laboratory tests that the infection has
      subsided. Bone grafting may be required for reconstruction. The use of autogenous
      bone calls for a second surgical site with an increased risk of morbidity. Using
      bone substitutes may reduce the need for autogenous bone. Stimulating factors,
      such as bone marrow concentrate (BMC) and demineralized bone matrix (DBM), may be
      used concomitantly with bone substitutes to facilitate bone regeneration. Case
      Report: The present report describes the case of a 38-year-old patient whose
      radius was fractured in a car accident. A first surgery involved stabilizing the
      reduced fracture with a plate, but an infection developed, and the bone did not
      heal. 3 months later, a second surgery followed, involving placing an antibiotic
      filled spacer. This did not cure the infection, so the spacer was replaced 3
      months later, and a second antibiotic was added. The patient also began taking
      oral antibiotics. 6 months later, the patient underwent vascularized fibular
      grafting. However, the graft did not integrate, and a non-union developed. A year
      later, the non-union was treated by grafting autogenous bone from the iliac
      crest, equine bone substitute, and equine DBM, in conjunction with autologous BMC
      and platelet-rich plasma. At the 6-month follow-up, the bone structure appeared
      to be successfully reconstructed. Conclusion: A graft made of a combination of
      materials with both biological and physical properties can be used to foster bone
      regeneration for the treatment ofparticularly challenging cases ofnon-unions.

PMID- 29600208
TI  - Intra-articular Osteoid Osteoma of Femoral Neck Region: A Simplified Treatment
      Strategy and Review of Literature.
AB  - Introduction: Proximal femur is the common site for localization of benign bone
      lesions, and the diagnosis is often delayed and potentially challenging due to
      their atypical presentations. Early diagnosis is difficult as intra-articular
      lesions often present with clinical and radiological features of inflammatory
      synovitis in the joint. Case Report: Two patients of intra-articular osteoid
      osteoma in proximal femoral presented with atypical features limb lengthening,
      minimal reactive bone sclerosis, and multifocal nidus. They were managed with
      anterior open approach, en bloc resection of the lesion, placement of autologous
      cortical graft, and prophylactic fixation with dynamic hip screw. Conclusion:
      Intra-articular osteoid osteomas in proximal femoral neck present differently,
      making the diagnosis and treatment challenging. Anterior open approach, en bloc
      resection of the lesion, reinforcement, and prophylactic fixation with dynamic
      hip screw is a reasonable option for managing these lesions which can be easily
      done in an average clinical setup.

PMID- 29600209
TI  - Multiple Recurrent Cyst Formation after Anterior Cruciate Ligament Reconstruction
      - A Case Report.
AB  - Introduction: Anterior cruciate ligament (ACL) reconstruction is a "daily"
      surgery. Nevertheless, pretibial cyst formation is a very rare complication and
      may appear years after the reconstruction. Even more infrequent is the recurrence
      of this complication. Case Report: We present a patient who developed a pretibial
      cyst 44 months after an ACL reconstruction and who underwent three open surgeries
      due to recurrence. Up to date, there are no symptoms or signals of cyst
      recurrence after 18 months of follow-up. Conclusion: Initial surgical resection
      might have failed due to insufficient surgical treatment. In case of suspicion of
      articular communication, we consider that the correct treatment is the resection
      of the cyst, proper curettage of the tunnel walls and a thorough filling of the
      space with bone graft. This course oftreatment may avoid a recurrence.

PMID- 29600210
TI  - Endoscopic Calcaneoplasty for Haglunds Excision Using Two Lateral Portals.
AB  - Introduction: The main objective of this case report is to demonstrate endoscopic
      calcaneoplasty (ECP) using two lateral portals. Case Report: The patient is
      middle-aged male aged 40 years, with higher basal metabolic index (BMI) and was
      diagnosed having a Haglund's bump and was on conservative treatment for a period
      of over 6 months, with minimal relief. We did ECP with the patient in lateral
      decubitus position using two lateral portals instead of using one medial and one
      lateral portal, his American Orthopaedic Foot and Ankle Society score has
      improved from 64 to 98, and his Fowler-Philip angle is reduced from 71 degrees 
      to 45 degrees . Conclusion: ECP using two lateral portals with patient in lateral
      position is comfortable for the patients with higher BMI and the surgical time
      can also be reduced. However, we need to perform more number of cases through
      this technique to conclude to the results. Endoscopic calcaneoplasty, two lateral
      portals, Haglund's bump.

PMID- 29600211
TI  - Unusual Presentation of Spinal Gout: 2 Cases Report and Literature Review.
AB  - Introduction: Gouty spondyloarthropathy is generally believed to be uncommon.
      Together with the fact that it can mimic a variety of disease entities, it
      imposes significant diagnostic challenge in our clinical practice. In this
      article, we report two patients diagnosed with spinal gout, and both were
      initially suspected to have a pyogenic infection. Case Reports: The first
      patient, a 66-year-old man, was admitted for fever and a short history of
      bilateral upper limb weakness. Clinical, biochemical, and radiological
      investigation results were suggestive of C5/6 infective spondylodiscitis with
      resultant cervical myelopathy. The second patient, a 68-year-old man, was
      admitted for fever and bilateral lower limb weakness and numbness compatible with
      cauda equina syndrome. Imaging showed L4/5 lytic spondylolisthesis with suspected
      abscesses formation around the pars defects. Both underwent emergency operations.
      Histological examinations of intraoperative specimens in both cases revealed
      tophaceous gout and microbiological studies were all negative. Urate-lowering
      agent was started for hyperuricemia. They both had partial neurological recovery.
      Conclusion: These two cases highlight how axial gout can mimic infective
      spondyloarthropathy clinically. In patients with multiple risk factors for gout
      presenting with back conditions, spinal gout should be considered as one ofthe
      differential diagnosis. With the availability of advanced imaging modality, dual
      energy computed tomography scan, pre-operative diagnosis of axial gout is now
      possible which may have implications on subsequent surgical approaches and
      medical treatment. Collaboration with the medical team to achieve good serum
      urate control is important to prevent disease recurrence.

PMID- 29600212
TI  - Upper Limb Phlegmasia Cerulea Dolens Secondary to Heparin-induced
      Thrombocytopenia: A Case Study.
AB  - Introduction: Phlegmasia cerulea dolens (PCD) is a rare pathology with a very
      high morbidity and mortality rate, which usually occurs in the lower limb. There
      is very little literature available to aid management. Case Report: We present a
      case of upper limb PCD in a 67-year-old female secondary to heparin-induced
      thrombocytopenia caused by warfarin bridging. She presented to the orthopedic
      team with upper limb compartment syndrome from a bleed around a peripherally
      inserted central catheter, for which she was urgently taken to the theater for
      fasciotomies. Postoperatively, the patient's platelets dropped and the upper limb
      pain and swelling continued; after conservative management and anticoagulation
      failed the patient had an upper limb amputation of her right arm. Conclusion:
      With limited guidelines and management options restricted by the large fasciotomy
      wounds, we believe amputation was the patients' best option.

PMID- 29600213
TI  - Rotatory Subluxation and Facet Deformity in the Atlanto-occipital Joint in
      Patients with Chronic Atlantoaxial Rotatory Fixation: Two Case Reports.
AB  - Introduction: The relationship between the morphometry of atlantoaxial joint and
      chronic atlantoaxial rotatory fixation (AARF) is well known, but disorders in the
      atlanto-occipital joint in chronic AARF are not fully elucidated. The authors
      report two rare cases of secondary deformities in the atlanto-occipital joint in
      chronic AARF. Case Reports: Two patients with chronic AARF were treated with
      closed manipulation, skull traction and halo-vest immobilization. Clinical
      outcomes and radiographs were reviewed retrospectively, focusing on pathological
      changes in the atlanto-occipital joint using multiplanar reconstruction computed
      tomography and three-dimensional computed tomography images. Case 1 (12-year-old
      girl) had rotatory subluxation with a superior facet deformity of the atlas in
      the atlanto-occipital joint before the initiation of treatment. After a series of
      conservative treatments, both atlantoaxial and atlanto-occipital rotatory
      fixation could not be reduced, and both the superior facet deformity of the atlas
      and osteoarthritic changes in the atlanto-occipital developed. She was monitored
      without surgery because the disorder progressed to the spontaneous fusion of the
      occipital bone to the axis. Case 2 (13-year-old boy) had rotatory subluxation
      without facet deformity of the atlas in the atlanto-occipital joint before the
      initiation of treatment. However, both the superior facet deformity of the atlas
      and osteoarthritic changes in the atlanto-occipital developed over time, and both
      atlantoaxial and atlanto-occipital rotatory fixation could not be reduced after a
      series of conservative treatments. He still had severe neck pain and severely
      restricted neck mobility and underwent spinal fusion. Conclusion: Atlanto
      occipital rotatory subluxation and facet deformity in the atlanto-occipital joint
      may occur after prolonged AARF. It is necessary to pay attention to pathological
      changes not only in the atlantoaxial joint but also in the atlanto-occipital
      joint, when orthopedic surgeons treat patients with AARF.

PMID- 29600214
TI  - An Intramuscular Chondrolipoma of the Scapula: A Case Report of a Rare Tumor in
      an Unusual Location.
AB  - Introduction: Chondrolipomas are rare benign mesenchymal tumors primarily
      occurring in the shoulder region. To the best of our knowledge, only one case of
      chondrolipoma arising from the shoulder has been reported. We herein report an
      intramuscular chondrolipoma located in an unusual area of the scapula. Our case
      is interesting because magnetic resonance imaging (MRI) that shows lipomatous
      tumor masses with cartilaginous nodules may mislead surgeons into not considering
      the possibility of chondrolipomas. Case Report: A 62-year-old female, without any
      systemic disease, trauma, or history of surgery, presented with a unique case of
      a large intramuscular chondrolipoma ofthe scapula. This protruding lump over the
      right shoulder was present for 3 months in the patient without pain or limited
      range of motion. A sonographic evaluation revealed a homogeneous hypoechoic
      lesion in the posterior right shoulder. MRI showed that the chondrolipoma
      measured 7.5 x 4.6 x 3.9 cm, without remarkable bony invasion, with high signal
      intensity over the mass in T1- weighted images, indicating cystic changes, and
      mild signal enhancement within the cyst in T2-weighted images. Surgical marginal
      excision was performed. We identified yellowish, greasy, and firm soft tissue and
      two cartilaginous nodules inside the lipomatous tissue. Pathological findings
      revealed mature adipose tissue with a fibrous capsule and true cartilage inside.
      Post-operative outpatient follow-up found no recurrence after 2 years.
      Conclusion: Intramuscular chondrolipoma arising from the shoulder has been rarely
      reported. MRI and sonography are helpful in the diagnosis.

PMID- 29600215
TI  - Tuberculous Tenosynovitis of the Wrist and the Hand: The 3 Anatomo- Clinical
      Forms Described by Kanavel (About 4 Cases).
AB  - Introduction: Tuberculous tenosynovitis localization is rare. This unusual
      presentation, often misunderstood, results in frequent misdiagnosis. We report 4
      cases of patients which represent the 3 anatomo-clinical forms described by
      Kanavel. The knowledge of its different manifestations will make it possible to
      recognize and to suspect the tuberculous origin. Case Report: This was a
      retrospective study from January 2006 to May 2017 which involved all patients
      received and treated with tuberculous tenosynovitis. Of the 4 case studies
      presented here, there were 3 men and 1 woman, aged, respectively, 23, 30, 40, and
      30 years of age. They were all immunocompetent. The onset was, respectively,
      about 12, 6, 4, and 8 months. The localization was on the wrist for 3 cases (2 on
      the right and 1 on the left) and one on the palmar face of the second ray on the
      right hand. Signs of median nerve compression were found in 2 cases. Surgery was
      extensive, with a complete debridement in 3 patients. For the last one, a simple
      recess was made associated with a bacteriological sampling. Biopsy was performed
      for all patients. In the anatomo-clinical study, we observed 1 case of
      serofibrinous synovitis, 2 cases of rice-like synovitis, and 1 case of caseous
      synovitis. A rupture of the tendon ofthe flexor carpi radialis was observed in 1
      case. All cases were confirmed histologically with the presence of granuloma
      gigantocellular with caseous necrosis. We have recorded 1 case ofbacteriological
      positivity in 3 cases requested. Patients had antituberculous chemotherapy after
      surgery for, respectively, 6, 8, 6, and 8 months. The progression was favorable
      with a regression of the signs of nerve compression. Revisited at, respectively,
      4, 3, 5 years, and 34 months, we did not record any recurrence. The mobility of
      the wrist was complete and partial for the finger. Conclusion: Tenosynovitis
      tuberculous treatment is mostly medical. Early diagnosis enables the treatment to
      be started as soon as possible to avoid extensive surgery. For this reason, it is
      currently essential to use high sensitivity diagnostic methods of such as the
      polymerase chain reaction method and the Genexpert in any suspicion of the
      disease.

PMID- 29600216
TI  - A Rare Case of Intraneural Neurothekeoma of Median Nerve Mimicking Carpal Tunnel
      Syndrome.
AB  - Introduction: Neurothekeomas are uncommon benign soft tissue tumors of the
      peripheral nerves. It is commonly found in the upper extremities and in the head
      and the neck region as a small, asymptomatic, and superficial nodule. Case
      Report: We report a rare case of intraneural neurothekeoma (2.8 chi 2.4 x 1.8 cm)
      of the median nerve at the wrist in a 56-year-old female, which presented with
      clinical features of carpal tunnel syndrome. Conclusion: Carpal tunnel syndrome
      caused by intraneural neurothekeoma has been rarely reported. Clinicians should
      be aware of this rare cause of carpal tunnel syndrome.

PMID- 29600217
TI  - Double Posterior Cruciate Ligament Sign on Magnetic Resonance Imaging: Imaging
      Variants, Mimics, and Clinical Implications.
AB  - Introduction: Double posterior cruciate ligament (PCL) sign is a sign on magnetic
      resonance imaging (MRI) which is suggestive of a bucket- handle tear (BHT) of the
      meniscus. We undertook this study to assess the presence of a double PCL sign and
      its correlation with arthroscopic findings. We also discussed the various mimics
      and variants of the double PCL sign. Case Report: All the patients with a double
      PCL sign on the MRI and who underwent knee arthroscopy between January 2012 and
      December 2016 (total of 5 cases, 4 males and one female) were included in the
      study. A correlation between the imaging findings and the MRI findings was done.
      All these young patients were aged between 22 and 41 years. Two patients
      underwent arthroscopic partial meniscectomy, and three patients underwent
      arthroscopic meniscal repair using all inside technique. Conclusion: It is
      necessary for the sports physician to understand and recognize this important and
      subtle sign on MRI which is suggestive of a BHT of the meniscus. It is also
      important to identify the mimics of this sign and its variants for better
      management planning and patient prognostication.

PMID- 29600218
TI  - Arthroscopic Fixation of Tibial Spine Avulsion in Skeletally Immature: The
      Technique.
AB  - Introduction: Tibial spine avulsion fracture is more frequent in children than
      adults. Various methods of fixation have been mentioned, but concern remains
      about crossing the tibial physis. We present a technique of arthroscopic fixation
      with non-absorbable suture. Case Report: A total of 10 skeletally immature
      patients with tibial spine avulsion of Meyers and McKeever Type 2 and 3 were
      included in the study. The knee was arthroscopically cleared of hematoma. The
      avulsed tibial insertion of anterior cruciate ligament was reduced and held in
      place with tibial guide. By drilling guide wire through the tibia, reduced
      fragment, a fiber wire was passed. The avulsed fragment was tied on a suture post
      on tibia. Outcome was evaluated radiologically and clinically (Lysholm score,
      pivot shift, and KT 1000) at 12 months after surgery. All cases attained full
      range of motion, stable knee and could return to previous level of activity. The
      mean pre-operative Lysholm score of 50.8 +/- 1.4 (35-59) improved to 96.3 +/- 2.9
      (92-100). The mean pre-operative anterior translation of tibia (measured by KT
      1000) of 7.6 +/- 1.26 improved significantly to mean of 3.3 +/- 0.82 mm after
      surgery. Conclusion: The presented technique of arthroscopic fixation of avulsed
      tibial spine is a simple technique that provides reproducible results. It also
      offers cost-effective secure fixation.

PMID- 29600219
TI  - Femoral Osteomyelitis Presenting as a Pathologic Fracture in a 53 Year Old Male:
      A Rare Case Report.
AB  - Introduction: Hematogenous osteomyelitis of long bones in immunocompetent adults
      is extremely rare and uncommonly presents as a pathological fracture. Case
      Report: A 53-year-old Caucasian male presented with an atraumatic mid-shaft femur
      fracture secondary to hematogenous osteomyelitis. The organism was found to be
      Streptococcus anginosus. The patient required multiple surgical debridements and
      was treated with an antibiotic-impregnated cement rod and external fixator along
      with IV Rocephin. Furthermore, the patient was on chronic Carbamazepine therapy
      for the refractory bipolar disorder. We discuss the effect cytochrome p450
      inducing medications have on bone health and how this may have contributed to
      this rare presentation of pathologic fracture. Conclusion: We report a rare case
      of femoral osteomyelitis presenting as a pathologic fracture. Treatment involves
      multiple surgeries and an extended recovery.

PMID- 29600220
TI  - Mycobacteria Intracellulare Spondylodiscitis Presenting as Progressive
      Consecutive Vertebral Sclerosis: A Case Report.
AB  - Introduction: Non-tuberculous mycobacteria (NTM) are slow-growing organisms
      affecting both immunocompromised and immunocompetent patients. As compared to
      tuberculosis, they pose formidable challenge in successful management beginning
      with diagnosis extending through its treatment. Case Report: Our case highlights
      unusual spinal presentation of NTM, intricacies in diagnosis, and successful
      management. Conclusion: As the prevalence of NTM is rising, it is important as
      clinicians to understand unique aspects which differ from tuberculosis for
      appropriate and successful treatment.

PMID- 29600222
TI  - A large cystic gastrointestinal stromal tumor within lesser sac: A diagnostic
      dilemma.

PMID- 29600221
TI  - Prognostic factors and outcomes in anaplastic gliomas: An institutional
      experience.
AB  - Background: There is lack of clear evidence and treatment guidelines for
      anaplastic gliomas (AGs) with very few studies focusing exclusively on these
      patients. The aim of the study was to analyze the clinical profile and survival
      in these patients. Materials and Methods: Patients of AGs treated with radiation
      and concurrent +/- adjuvant chemotherapy from January 2010 to December 2015 were
      analyzed. Statistical analysis was done using SPSS version 20 software. Results:
      A total of 100 patients were included in the study. The median age was 35 years
      (range 6-68 years). Eighty-four patients had follow-up details and were included
      for survival analysis. The 5-year overall survival (OS) was 58%. Age,
      presentation with seizures, and focal neurological deficit were not found to
      significantly influence survival. The 5-year survival for oligodendroglioma and
      astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance
      Score (KPS) of >=70 had a significantly better 5-year OS (65%) as compared to
      those with KPS <70 (33%) (P = 0.000). The use of adjuvant temozolomide (TMZ)
      showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive
      adjuvant chemotherapy (P = 0.018). Patients receiving both concurrent and
      adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two
      patients had recurrence with average time to recurrence being 37 months. Fourteen
      patients underwent salvage surgery and two patients received reirradiation.
      Conclusions: OS significantly correlated with KPS and receipt of concurrent and
      adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and
      adjuvant TMZ should be the standard of care for AGs.

PMID- 29600223
TI  - Estrogen receptor and progesterone receptor status of breast cancer patients of
      eastern India: A multi-institutional study.
AB  - Context: There is a paucity of any significant data on the estrogen receptor (ER)
      and progesterone receptor (PR) status of breast cancer patients from the eastern
      part of India. Aims: This study aims to document the ER and PR status of breast
      cancer patients in the eastern Indian population, as catered by two premier
      tertiary care hospitals in Kolkata. Subjects and Methods: All breast cancer
      patients registered between January 1, 2013 and December 31, 2015, in the
      Departments of Oncology, of IPGMER and SSKM Hospitals and R. G. Kar Medical
      College and Hospital, Kolkata, who had at least undergone a core biopsy or
      surgery, were analyzed retrospectively for documentation of their ER and PR
      status, using the 2010 American Society of Clinical Oncology/College of American
      Pathologists (ASCO/CAP) interpretation guidelines. Results: Over a period of 3
      years, a total of 927 patients were included for the study. A total of 825 (89%)
      patients had their ER and PR data available for evaluation. ER and PR positive
      was seen in 312 (37.82%) patients, ER and PR negative in 399 (48.36%) patients,
      ER positive and PR negative in 71 (8.6%) patients, and ER negative and PR
      positive results was found in 43 (5.21%) patients. Conclusions: This is the first
      multi-institutional documentation of ER and PR status from eastern India, having
      a modest number of patients and one of the earliest documentations using the
      latest ASCO/CAP interpretation guidelines. These findings resemble the data from
      the south and also reiterate the fact that majority of the Indian breast cancer
      patients are still ER and PR negative in spite of the changes in the
      interpretation guidelines.

PMID- 29600224
TI  - Estrogen receptor, Progesterone receptor, and human epidermal growth factor
      receptor-2 status in breast cancer: A retrospective study of 5436 women from a
      regional cancer center in South India.
AB  - Aim: The aim of the study was to analyze the estrogen receptor (ER), progesterone
      receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7
      years in South Indian women with breast cancer. Further analysis of a subgroup
      was done to study clinically defined subtypes and the role of preanalytical
      factors in needle core biopsies (NCBs) and excised specimens. Materials and
      Methods: This was a retrospective study from January 2010 to December 2016.
      Patients diagnosed with invasive breast cancer and available immunohistochemistry
      (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year
      2016 were analyzed further to observe the impact of preanalytical factors on the
      IHC staining patterns and surrogate status. Results: A total of 5436 patients
      were included with a median age of 48 years. Among these, 65% were <= 55 years.
      The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2
      positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR
      positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in
      patients <56 years and over 55 years, respectively (P < 0.001). There was an
      increase in HR positivity and decrease in TNBCs over time. There was no
      significant difference in the staining patterns in NCBs and excised specimens.
      Conclusion: With time, there is an increase in hormone-positive tumors which may
      be attributed to better IHC techniques and tissue handling. There was no
      statistical difference in the patterns of ER, PR, and HER2 immunostaining in core
      biopsy and excised specimens.

PMID- 29600225
TI  - Comparison of health-related quality of life with epirubicin, cisplatin plus 5
      fluorouracil and docetaxel, cisplatin plus 5-fluorouracil chemotherapy regimens
      as first-line systemic therapy in locally advanced inoperable or metastatic
      gastric or gastro-esophageal junction adenocarcinoma: A prospective study from
      South India.
AB  - Background: Health-related quality of life (HRQOL) is an important oncologic end
      point for upper gastrointestinal malignancies. Unfortunately, till date, there is
      no published prospective data from India, comparing the HRQOL parameters between
      first-line chemotherapy regimens in advanced/metastatic gastric cancer. Materials
      and Methods: The present study aimed to compare the HRQOL of first-line systemic
      chemotherapy with epirubicin, cisplatin plus 5-FU (ECF) and docetaxel, cisplatin
      plus 5-FU (DCF) regimens in patients with locally advanced inoperable or
      metastatic gastric or gastro-esophageal junction adenocarcinoma. The secondary
      end points were overall response rate, progression-free survival (PFS), overall
      survival (OS), and toxicity profile. Results: Between December 2014 and December
      2016, 65 patients were treated with ECF (n = 34) or DCF (n = 31) regimen. The
      baseline HRQOL scores were comparable between the two study groups, with the
      exception of significantly poor pain and sleep difficulties symptom score in the
      DCF group. After three cycles of treatment, both the groups showed improvements
      in most of the quality of life (QOL) parameters including global QOL score,
      compared with their baseline status. After six cycles of chemotherapy, the ECF
      group showed nonsignificant deterioration for most of the QOL parameters; but on
      the contrary, the DCF group maintained improved scores for most of the QOL
      parameters. The median survival until a definitive deterioration of global QOL
      score was significantly better in the DCF arm in comparison to the ECF arm (7.1
      vs. 5.6 months, respectively, P = 0.000). The median OS was 9.2 months with ECF
      and 12.5 months with DCF regimen (P = 0.000), while median PFS was 5.7 and 7.4
      months with ECF and DCF regimens, respectively (P = 0.002). Conclusions: This
      prospective study highlighted a better impact of DCF chemotherapy on the HRQOL of
      patients with advanced/metastatic gastric cancer and showed the importance of QOL
      assessments in clinical trials to complement the risk-benefit judgment.

PMID- 29600226
TI  - Assessment of quality of life in resectable gastric cancer patients undergoing
      chemoradiotherapy as adjuvant treatment.
AB  - Introduction: Quality of life (QOL) is increasingly recognized as an important
      endpoint in cancer therapies. However, few data are available on QOL in patients
      who have received radiotherapy as adjuvant treatment for cancer stomach. Methods:
      Thirty patients who underwent curative resection were enrolled and received
      chemoradiotherapy (45 Gy in 25 fractions using three-dimensional conformal
      radiotherapy technique), together with 5-fluorouracil and leucovorin. The
      European Organization for Research and Treatment of Cancer QOL questionnaire C30
      and STO Q22 was assessed at four time points: pre- and postchemoradiotherapy and
      at 1-month and 6-month follow-up. Results: Mean age of the patients was 54 years.
      Male:female ratio was 4:1. Stage II and Stage III disease was present in 60% and
      30% of patients, respectively. All patients were able to complete the
      chemoradiotherapy protocol. Our study found out significant impairment in QOL for
      emotional functioning, fatigue, nausea and vomiting and dyspnea. Results showed
      that QOL levels decrease postchemoradiotherapy; however, QOL levels returned to
      baseline at 1-month and 6-month follow-up period. Conclusion: Chemoradiotherapy
      as adjuvant treatment for cancer stomach patients who have undergone resection
      with curative intent is a safe and well-tolerated regimen with respect to QOL.

PMID- 29600227
TI  - Pulmonary artery pseudoaneurysm secondary to metastatic breast cancer.

PMID- 29600228
TI  - Incidental gallbladder carcinoma: Utility of histopathological evaluation of
      routine cholecystectomy specimens.
AB  - Background: Incidental gallbladder carcinoma (IGBC) is rare cancer diagnosed
      during or after cholecystectomy done for benign gallbladder disease. The concern
      whether routine histopathological examination is needed for all cholecystectomy
      specimens still remains debatable. Materials and Methods: Twenty patients
      diagnosed with IGBC over a period of 2 years were retrospectively reviewed.
      Clinical details including clinical presentation, preoperative ultrasound (USG)
      findings, and macroscopic features were retrieved. Diagnosis of IGBC was
      confirmed on microscopic examination, and staging was done using the tumor node
      metastasis staging system. Results: Of the 4800 cholecystectomy specimens
      retrieved, diagnosis of IGBC was rendered in twenty cases (0.41%). Mean patient
      age was 50.65 years with a female preponderance. Preoperative USG detected an
      increase in wall thickness in six cases (30%) in contrast to gross examination
      which revealed the same in 55% (11/20) cases. Mucosal ulceration was observed in
      two cases (10%) of IGBC and seven cases (35%) did not reveal any preoperative or
      macroscopic findings suggestive of malignancy. Associated cholelithiasis was
      observed in 14 cases. Final diagnosis of IGBC was made on histomorphological
      assessment with tumor cells infiltrating the lamina propria in three cases
      (pT1b), muscularis propria in 15 cases (pT1b), and serosa in the remaining 2
      cases (pT2). Conclusion: IGBC is a clinical masquerader which often evades the
      eye of a radiologist and comes as pathological surprise. Histopathological
      examination of cholecystectomy specimens remains the gold standard for the
      detection of this occult, yet notorious malignancy and assessment of the depth of
      invasion in IGBC guide further management.

PMID- 29600229
TI  - Epidemiology of liver cancer in Nile delta over a decade: A single-center study.
AB  - Background: In Egypt, there has been a remarkable increase in the proportion of
      hepatocellular carcinoma (HCC) among chronic liver diseases patients. This rising
      proportion may be explained by the increasing risk factors as hepatitis C virus
      (HCV) infection, hepatitis B virus (HBV) infection, improvement of the diagnostic
      tools of HCC as well as the extended survival among patients with cirrhosis to
      allow time for some of them to develop HCC. The aim of this study was to study
      the epidemiology of HCC in Nile delta over the last decade. Methods: The study
      was carried out on patients diagnosed as HCC in liver cancer clinic in Tanta
      University Hospital, Egypt, from January 2005 to January 2015. This retrospective
      study reviewed the files of HCC patients with special stress on age, sex,
      residence, occupation, smoking, and viral markers. Results: Over the last decade,
      1440 HCC patients were diagnosed or referred to liver cancer clinic in Tropical
      Medicine Department in Tanta University Hospital from January 2005 to January
      2015. The mean age of HCC patients was 56.13 +/- 9.53 years. Nearly, half of the
      patients with HCC were smokers and quarter of HCC patients were diabetics. HBV
      surface antigen-positive patients were only 3.26%, and the majority of patients
      were HCV-Ab positive (94.86% of patients). Conclusions: In Nile delta, hepatitis
      C rather than hepatitis B was linked to the development of HCC in our region
      which may be related to the high prevalence of HCV in this area.

PMID- 29600230
TI  - Standard-dose versus high-dose radiotherapy with concurrent chemotherapy in
      esophageal cancer: A prospective randomized study.
AB  - Objective: The objective of this study is comparision of local and distant
      control rates with high-dose versus standard-dose radiotherapy along with
      concurrent chemotherapy in esophageal cancer - a prospective randomized study.
      Materials and Methods: Histologically proven Stage I-III patients with carcinoma
      esophagus were randomized into two groups. One group has been treated with
      standard-dose radiotherapy, i.e., a total dose of 50.4 Gy (1.8 Gy/day, 28#, 5
      days/week). The other group (study arm) has received high-dose radiotherapy, i.e.
      a total dose of 64.8 Gy (1.8 Gy/day, 36#, 5 days/week). Both groups have received
      2 cycles of 3 weekly concurrent chemotherapy (cisplatin 75 mg/m[2] on day 1 and 5
      fluorouracil 750 mg/m[2] continuous intravenous infusion over 24 h on day 1-4).
      Follow-up response evaluation was done by both endoscopy and computed tomography
      scan after 6-8 weeks and after 2 months thereafter. Results: Out of a total of 28
      patients, 68% showed a complete response, 14% showed partial response, and 18%
      patients developed progressive disease at first and subsequent follow up (median
      follow-up of 21 months). Among the complete response patients, rates were higher
      in high-dose group compared to standard-dose radiotherapy group (71% vs. 64%, P =
      0.38). Treatment-related toxicities were acceptable in both groups. Conclusion:
      High-dose radiotherapy with concurrent chemotherapy seems to be more effective
      with acceptable toxicity in our study. However, further follow-up and large
      sample size may be required to validate the current study conclusion.

PMID- 29600231
TI  - Outcomes of carcinosarcoma in a tertiary care institution in India.
AB  - Background: Carcinosarcoma is a rare malignancy, and reports are often mixed
      along with other sarcomas. The literature on uterine carcinosarcoma per se is
      sparse. Aims: This study aims to evaluate the demography, survival, and optimal
      treatment strategy of uterine carcinosarcoma. Settings and Design: A tertiary
      care center in India. The study design was descriptive with survival analysis.
      Materials and Methods: The medical records of all 18 patients admitted with
      uterine carcinosarcoma between January 2011 and December 2015 were reviewed.
      Baseline characteristics and outcomes were studied. Survival analysis was done
      using the Kaplan-Meier method and compared between treatment groups using the Log
      rank test. Results: The total number of uterine malignancies operated in our
      center over this time period was 311 of which 18 were carcinosarcomas (5.7%).
      Median age of presentation was 61 years (36-77 years). Most women (94%) were
      postmenopausal and 67% of them presented with postmenopausal bleeding. Over half
      of the patients (56%) presented late (Stage III or IV). Only 11 (61%) had
      adjuvant treatment and 7 patients had expired at the time of follow-up. The
      median survival was 284 days (95% confidence interval 107-461). Patients who
      received adjuvant therapy did better compared to those who did not (P = 0.036).
      Conclusions: Carcinosarcomas are aggressive tumors of postmenopausal women who
      present with bleeding or discharge per vaginum. In spite of adequate surgical
      staging followed by adjuvant therapy, survival remains poor. Improvements in
      early detection and optimal therapy need to be made.

PMID- 29600232
TI  - Geographical distribution of cervical cancer in Odisha: A 5-year retrospective
      study at a regional cancer center.
AB  - Background: Cancer cervix and breast are the two major female health problems in
      India. A hospital-based, 5-year (2010-2014) retrospective study was conducted at
      a regional cancer center of Odisha to analyze the present burden of cancer cervix
      in this state, which has a population of more than 45.5 million at present.
      Materials and Methods: All the patients suffering from cancer cervix that was
      treated by radiotherapy during 2010-2014 at this center were analyzed year wise
      for age, stage of disease, and native area. Results: Based on the Census 2011
      data, it was calculated and found that from the low-literacy area on an average
      of 4.62 cervical cancer patients per million, from the medium-literacy area 6.56
      patients per million, and from high-literacy area 19.11 patients per million of
      population have received radiotherapy in this hospital. More than 60% of patients
      with cervical cancer were from stage IIIB and in the age group of 50-55 years.
      Discussion: Odisha has 83.7% female population in rural areas with literacy rate
      below 50%. Due to lack of awareness and unavailability of cancer care facilities
      at their reach, they mainly depend on various alternative medicines in
      unscientific manner for their health care. Conclusion: Strengthening of existing
      regional cancer center, development of oncology wings in all medical college
      hospitals by providing basic radiotherapy facilities, emphasizing more on
      district cancer control programs, decentralizing of NGO schemes, and facilitating
      with more cancer screening and awareness programs may help better registration,
      prevention, and treatment of cancer in Odisha.

PMID- 29600233
TI  - Translation and validation of European Organization for Research and Treatment
      for Cancer quality of life questionnaire-OV-28 module into Indian languages
      (Hindi and Marathi) to study quality of life of ovarian cancer patients from a
      tertiary care cancer center.
AB  - Aim: The aim is to translate and validate the European Organization for Research
      and Treatment for Cancer (EORTC) ovarian cancer (OC) module (OV-28) into Hindi
      and Marathi to use for patients and scientific community. Methods and Results:
      The EORTC OV-28 was translated into Hindi and Marathi languages using prescribed
      guidelines by the EORTC. The process included forward translation by four
      translators (2 each for Hindi and Marathi). The questionnaires obtained were then
      given to independent backward-translators who then translated them back into
      English. These 2 questionnaires were then compared with the original EORTC
      questionnaire and the second intermediate questionnaires were formed. The second
      intermediate questionnaire was subsequently administered in twenty patients (10
      each for Hindi and Marathi) diagnosed with OC who had never seen the
      questionnaire before, for pilot testing. Each of these ten patients after filling
      up the questionnaire themselves was then interviewed for any difficulty
      encountered during the filling up of the questionnaires. These were in the form
      of specific modules including difficulty in answering, confusion while answering,
      and difficulty to understand, whether the questions were upsetting and if
      patients would have asked the question in any different way. The suggestions were
      incorporated into the second intermediate questionnaires to form the final Hindi
      and Marathi ON-28 questionnaires. These questionnaires were then sent to the
      EORTC for the final approval to be used in clinical studies. Conclusion: We have
      successfully translated EORTC OV-28 module into Hindi and Marathi languages, and
      EORTC approved them to be used in clinical practice and studies for OC patients.

PMID- 29600234
TI  - Prophylactic salpingectomy and ovarian cancer: An evidence-based analysis.
AB  - Introduction: One of the ovarian carcinogenesis theories was the presence of
      premalignant cells in the epithelium of the fallopian tube. Therefore, the
      prophylactic salpingectomy during benign gynecological surgery is now expected as
      the attempt to reduce the ovarian cancer incidence. We studied the effect of
      prophylactic bilateral salpingectomy (PBS) in reducing the ovarian cancer
      incidence. Methods: This evidence-based report resulted from critical appraisal
      of 5 articles. It is aimed to answer our clinical question, can bilateral
      prophylactic salpingectomy reduce the incidence of ovarian cancer among women
      underwent hysterectomy for benign condition or permanent contraception surgery?
      The search was conducted on the Cochrane Library(r), PubMed(r), and Embase(r)
      using keywords of "prophylactic salpingectomy," and "ovarian cancer incidence."
      Reference lists of relevant articles were searched for other possibly relevant
      articles. Results: Five studies were included in our appraisal. The incidence of
      ovarian cancer among women underwent prophylactic salpingectomy is lower compared
      to women who were not underwent any intervention (2.2% to 13% and 4.75% to
      24.4%). The salpingectomy may reduce 29.2% to 64% of ovarian cancer incidence. No
      significant effect of PBS to ovarian function, quality of life, sexuality,
      surgery duration, and its cost-effective profile were also found throughout our
      literature study. Conclusion: PBS is suggested to be performed for women during
      benign gynecological surgery as a primary preventive strategy of ovarian cancer.
      PBS is a cost-effective procedure, risk-reducing for ovarian cancer and has no
      significant effect to the ovarian function.

PMID- 29600235
TI  - Assessment of oral mucositis during concurrent chemoradiation of head and neck
      cancers using patient-reported measurement scale.
AB  - Introduction: Oral mucositis (OM) is a major challenge encountered in concurrent
      radiochemotherapy for the treatment of head and neck cancers. The patient
      reported OM symptoms scale (PROMS) was administered on these patients. The
      objective was to develop the similar scale in an Indian language and prescribe it
      population undergoing cancer treatment. Materials and Methods: PROMS scale was
      converted to Telugu language. Fifty-one patients took part in the study. All of
      them answered the 10-point questions marked their responses on 100 mm visual
      analog scale after thorough oral examination using WHO grading by the same
      examiner. Results: Internal consistency of Cronbach's alpha on PROMS scale was
      0.81-0.97. The questionnaire study was administered on 35 males and 16 females
      with the mean age of 54.9 +/- 11.8. The decrease in the total PROMS score was
      marked on day 35 in almost all patients, with a mean value of 34.04 +/- 30.2
      followed by a further significant decrease on day 60 (follow-up) with a mean of
      3.71 +/- 7.8. The PROMS scores correlated strongly with the clinician-rated OM
      scores during the first 35 weeks from the baseline at 0.84 with P < 0.01 and poor
      correlation was at day 60, i.e. 0.32 with P < 0.05 using Spearman's Rho
      correlation. Conclusion: The study showed a good correlation between patient
      reported items and clinical score by standard grading scale. This questionnaire
      may not be a sole guide in assessing the severity of OM but could be definitely
      used as an adjunct to clinical oral examination at assessment levels.

PMID- 29600236
TI  - Squamous cell carcinoma of buccal mucosa: An analysis of prognostic factors.
AB  - Introduction: Carcinoma of the buccal mucosa is the most common oral cavity
      cancer in the Indian subcontinent. The aim of this study was to analyze the
      outcome and evaluate prognostic factors in surgically treated buccal mucosa
      squamous cell carcinoma (BMSCC) patients. Materials and Methods: A retrospective
      study was performed by reviewing the medical records of 409 pathologically proven
      buccal mucosa cancer patients, who were diagnosed and surgically treated in Tata
      Memorial Hospital between January 1, 2006, and December 31, 2008. Results: The
      overall 5-year survival of the cohort was found to be 54.1%. The stage-wise
      survival rate for tumor, node, metastasis (TNM) Stage I, II, III, and IV patients
      was found to be 85.2%, 82.9%, 56.3%, and 42.6% (P < 0.00), respectively. On
      multivariate Cox proportional hazard analysis, the presence of comorbidity,
      histological tumor size, pathological lymph node status, tumor differentiation,
      perineural invasion, and extracapsular spread were found to be independently
      associated with overall survival. Conclusion: BMSCC is an aggressive malignant
      tumor. In addition to TNM classification, other clinical and pathological factors
      also have a significant role in BMSCC prognostication. Hence, there is a need to
      move beyond TNM and develop a more inclusive, flexible, and easy to use
      prognostic system.

PMID- 29600237
TI  - Prospective study of sequential volumetric changes of parotid gland in early
      oropharyngeal carcinoma patients treated by intensity-modulated radiation
      therapy: An institutional experience.
AB  - Aims and Objectives: During course of radiation therapy, anatomical variations
      occur risking overdose of parotid gland. We tried to quantify volume of parotid
      gland and mean dose to parotid gland after every 10 fractions (#). Materials and
      Methods: We conducted the prospective study from July 2016 to May 2017 in 25
      patients of early-stage oropharyngeal carcinoma. Patients had Karnofsy
      Performance Score of 80-100, median age was 54 years, and 18 patients were males.
      Patients were planned with intensity-modulated radiation therapy planning with
      dose as 66 Gy/30# to planning target volume (PTV) including primary and 54 Gy/30#
      to PTV-nodal including elective neck irradiation. After each 10#, replanning was
      done, and variations in parotid volume were studied including Dmean (mean dose to
      parotids) and D50 (the dose delivered to 50% of volume). Other tumor
      characteristic like PTV of primary was also assessed and minimum PTV volume
      covered by 95% isodose line was kept as 95%. Results: Average parotid volumes
      decreased by the mean value of 10% and 6% for the left and right parotids,
      respectively, and PTV of primary target decreased by mean of 13%. The difference
      in Dmean doses to parotid glands was 32% and 42% and difference in D50 dose was
      30% and 35% on the left and right side, respectively. Conclusions: The parotid
      volumes differ considerably during adaptive planning done after every ten
      fractions. These differences in parotid volumes and doses received to parotid
      glands play a significant role in the risk of xerostomia observed during later
      follow-up.

PMID- 29600238
TI  - Efficacy and tolerability of bortezomib and dexamethasone in newly diagnosed
      multiple myeloma.
AB  - Background: Outcome in multiple myeloma (MM) has improved substantially over
      recent years as a result of the availability of multiple novel agents with
      acceptable safety profile. Study Design: Prospective observational study at a
      tertiary care institute. Methods: Twenty-five newly diagnosed patients of MM were
      treated with bortezomib and dexamethasone induction with monitoring for response
      and safety, followed by peripheral blood autologous stem cell transplant (PBASCT)
      in eligible patients or maintenance. Results: Out of 25 patients, 32% attained
      complete response (CR), 56% very good partial response (VGPR), 4% PR, and 8%
      showed no response. The overall response rate was 92%. In our study, 56% of
      patients showed hematological side effects, out of which thrombocytopenia was
      seen in 32%, anemia in 16%, and leukopenia in 8%. Six patients developed
      bortezomib-induced peripheral neuropathy, out of which four had grade 1 (66.66%),
      one had grade 2 (16.66%), and 1 (16.66%) had grade 3 toxicity. Sixteen patients
      were eligible for PBASCT, out of which eight patients received this therapy while
      as remaining eight patients opted for two more cycles of induction therapy
      followed by maintenance. After completing 18 months of maintenance, all the eight
      patients who underwent PBASCT were in CR. Out of the 15 patients who did not
      receive PBASCT five attained CR, eight VGPR while as two patients relapsed.
      Conclusion: Bortezomib plus dexamethasone is highly effective and well-tolerated
      regimen for frontline treatment of MM with a higher quality of response in an
      advanced stage and renal failure patients.

PMID- 29600239
TI  - Clinical outcome study of crizotinib in immunohistochemistry-proven echinoderm
      microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene
      among Indian patients with adenocarcinoma lung.
AB  - Aims: The anaplastic lymphoma kinase (ALK) Break Apart FISH Probe Kit and Ventana
      anti-ALK (D5F3) CDx immunohistochemistry (IHC) assay are the Food and Drug
      Administration-approved companion diagnostic for targeted therapy with the ALK
      inhibitor crizotinib in lung cancers. The aim of this study was to assess the
      efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven
      echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among
      Indian patients with adenocarcinoma lung in the routine clinical practice.
      Subjects and Methods: Patients with nonsmall cell lung cancer (NSCLC),
      adenocarcinoma histology, whose tumors were found to be positive for EML4-ALK
      fusion gene using IHC, were considered for this study. IHC analysis was performed
      using a Ventana automated immunostainer (Benchmark XT). Detection was performed
      using Optiview DAB detection and amplification kit. Results: A total of 25 NSCLC
      adenocarcinoma patients were included in the study. There were 14 (56%) women and
      10 (44%) men with a median age of 53 years. All patients had Stage IV disease at
      the time of initiation of crizotinib therapy. One patient achieved complete
      response and 20 achieved response rate (PR) for an overall PR of 84%. The median
      progression-free survival (PFS) was 11.8 months and median overall survival (OS)
      was 20.6 months. Two (8%) patients experienced severe hepatotoxicity requiring
      permanent discontinuation of crizotinib therapy. Conclusions: A very high PR,
      PFS, and OS achieved in our study population indicates that IHC can accurately
      identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are
      responsive to ALK inhibitors such as crizotinib. IHC should be considered as a
      cost-effective alternative to FISH, especially in low-resource countries.

PMID- 29600240
TI  - Neoadjuvant chemotherapy in locally advanced invasive lobular carcinoma: A
      limited institutional experience.

PMID- 29600241
TI  - A Standardized Needs Assessment Tool to Inform the Curriculum Development Process
      for Pediatric Resuscitation Simulation-Based Education in Resource-Limited
      Settings.
AB  - Introduction: Under five mortality rates (UFMR) remain high for children in low-
      and middle-income countries (LMICs) in the developing world. Education for
      practitioners in these environments is a key factor to improve outcomes that will
      address United Nations Sustainable Development Goals 3 and 10 (good health and
      well being and reduced inequalities). In order to appropriately contextualize a
      curriculum using simulation, it is necessary to first conduct a needs assessment
      of the target learner population. The World Health Organization (WHO) has
      published a tool to assess capacity for emergency and surgical care in LMICs that
      is adaptable to this goal. Materials and methods: The WHO Tool for Situational
      Analysis to Assess Emergency and Essential Surgical Care was modified to assess
      pediatric resuscitation capacity in clinical settings in two LMICs: Uganda and
      Myanmar. Modifications included assessment of self-identified learning needs,
      current practices, and perceived epidemiology of disease burden in each clinical
      setting, in addition to assessment of pediatric resuscitation capacity in regard
      to infrastructure, procedures, equipment, and supplies. The modified tool was
      administered to 94 respondents from the two settings who were target learners of
      a proposed simulation-based curriculum in pediatric and neonatal resuscitation.
      Results: Infectious diseases (respiratory illnesses and diarrheal disease) were
      cited as the most common causes of pediatric deaths in both countries. Self
      identified learning needs included knowledge and skill development in pediatric
      airway/breathing topics, as well as general resuscitation topics such as CPR and
      fluid resuscitation in shock. Equipment and supply availability varied
      substantially between settings, and critical shortages were identified in each
      setting. Current practices and procedures were often limited by equipment
      availability or infrastructural considerations. Discussion and conclusion:
      Epidemiology of disease burden reported by respondents was relatively consistent
      with WHO country-specific UFMR statistics in each setting. Results of the needs
      assessment survey were subsequently used to refine goals and objectives for the
      simulation curriculum and to ensure delivery of pragmatic educational content
      with recommendations that were contextualized for local capacity and resource
      availability. Effective use of the tool in two different settings increases its
      potential generalizability.

PMID- 29600242
TI  - Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in
      Neonates.
AB  - The biological role of the ductus arteriosus (DA) in neonates varies from an
      innocent bystander role during normal postnatal transition, to a supportive role
      when there is compromise to either systemic or pulmonary blood flow, to a
      pathological state in the presence of hemodynamically significant systemic to
      pulmonary shunts, as occurs in low birth weight infants. Among a wide array of
      clinical manifestations arising due to the ductal entity, systemic circulatory
      insufficiency and hypotension are of significant concern as they are particularly
      challenging to manage. An understanding of the physiologic interplay between the
      DA and the circulatory system is the key to developing appropriate targeted
      therapeutic strategies. In this review, we discuss the relationship of systemic
      hypotension to the DA, emphasizing the importance of critical thinking and a
      precise individual approach to intensive care support. We particularly focus on
      the variable states of hypotension arising directly due to a hemodynamically
      significant DA or seen in the period following successful surgical ligation. In
      addition, we explore the mechanistic contributions of the ductus to circulatory
      insufficiency that may manifest during the transitional period, states of
      maladapted transition (such as acute pulmonary hypertension of the newborn), and
      congenital heart disease (both ductal dependent and non-ductal dependent
      lesions). Understanding the dynamic modulator role of the ductus according to the
      ambient physiology enables a more precise approach to management. We review the
      pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic
      intervention for the spectrum of DA-related circulatory compromise.

PMID- 29600243
TI  - Reflections of Homeless Women and Women with Mental Health Challenges on Breast
      and Cervical Cancer Screening Decisions: Power, Trust, and Communication with
      Care Providers.
AB  - This study conducted in Toronto, Canada, explored the perceptions of women living
      in homeless shelters and women with severe mental health challenges about the
      factors influencing their decision-making processes regarding breast and cervical
      cancer screening. Twenty-six in-depth qualitative interviews were conducted. The
      objectives of this research were (i) to provide new insights about women's
      decision-making processes, (ii) to describe the barriers to and facilitators for
      breast and cervical cancer screening, and (iii) to offer recommendations for
      future outreach, education, and screening initiatives developed specifically for
      under/never-screened marginalized women living in urban centers. This exploratory
      study utilized thematic analysis to broaden our understanding about women's
      decision-making processes. A constructed ontology was used in an attempt to
      understand and describe participants' constructed realities. The epistemological
      framework was subjective and reflected co-created knowledge. The approach was
      hegemonic, values-based, and context-specific. The aim of the analysis was to
      focus on meanings and actions with a broader view to identify the interplay
      between participants' narratives and social structures, medical praxis, and
      policy implications. Results from 26 qualitative interviews conducted in 2013
      2014 provided insights on both positive and negative prior cancer screening
      experiences, the role of power and trust in women's decision-making, and areas
      for improvement in health care provider/patient interactions. Outcomes of this
      investigation contribute to the future development of appropriately designed
      intervention programs for marginalized women, as well as for sensitivity training
      for health care providers. Tailored and effective health promotion strategies
      leading to life-long cancer screening behaviors among marginalized women may
      improve clinical outcomes, decrease treatment costs, and save lives.

PMID- 29600244
TI  - Extending beyond Policy: Reaching UNAIDS' Three "90"s in Malawi.
AB  - Malawi, like other countries with a generalized HIV epidemic, is striving to
      reach the ambitious targets set by UNAIDS known as the three 90's for testing,
      provision of antiretroviral therapy and viral suppression. Assisted by Malawi's
      progressive policies on HIV/AIDS, it appears possible that Malawi will attain
      these targets, but only by employing innovative program approaches to service
      delivery which help fill policy gaps. This article describes how a dedicated
      cadre of layperson testers and HIV-positive peers appears to have helped attain
      increases in HIV and viral load testing and retention in care in four districts
      in Malawi, and situates these innovations in a policy framework analysis.

PMID- 29600245
TI  - Viscosity, Conductivity, and Electrochemical Property of Dicyanamide Ionic
      Liquids.
AB  - The instructive structure-property relationships of ionic liquids (ILs) can be
      put to task-specific design of new functionalized ILs. The dicyanamide (DCA) ILs
      are typical CHN type ILs which are halogen free, chemical stable, low-viscous,
      and fuel-rich. The transport properties of DCA ionic liquids are significant for
      their applications as solvents, electrolytes, and hypergolic propellants. This
      work systematically investigates several important transport properties of four
      DCA ILs ([C4mim][N(CN)2], [C4m2im][N(CN)2], N4442[N(CN)2], and N8444[N(CN)2])
      including viscosity, conductivity, and electrochemical property at different
      temperatures. The melting points, temperature-dependent viscosities and
      conductivities reveal the structure-activity relationship of four DCA ILs. From
      the Walden plots, the imidazolium cations exhibit stronger cation-anion
      attraction than the ammonium cations. DCA ILs have relatively high values of
      electrochemical windows (EWs), which indicates that the DCA ILs are potential
      candidates for electrolytes in electrochemical applications. The cyclic
      voltammograms of Eu(III) in these DCA ILs at GC working electrode at various
      temperatures 303-333 K consists of quasi-reversible waves. The electrochemical
      properties of the DCA ILs are also dominated by the cationic structures. The
      current intensity (ip), the diffusion coefficients (Do), the charge transfer rate
      constants (ks) of Eu(III) in DCA ILs all increased with the molar conductivities
      increased. The cationic structure-transport property relationships of DCA ILs
      were constructed for designing novel functionalized ILs to fulfill specific
      demands.

PMID- 29600246
TI  - Evolution of Sangiovese Wines With Varied Tannin and Anthocyanin Ratios During
      Oxidative Aging.
AB  - Changes in phenolic compounds, chromatic characteristics, acetaldehyde, and
      protein-reactive tannins associated with oxidative aging were studied in
      Sangiovese wines with varied tannin T/anthocyanin A ratios. For this purpose,
      three Sangiovese vineyards located in Tuscany were considered in the 2016
      vintage. To obtain wines with different T/A ratios, two red wines were produced
      from each vinification batch: a free run juice with a lower T/A ratio and a marc
      pressed wine with a higher T/A ratio. An overall of six wines with T/A ratios
      ranging between 5 and 23 were produced. An oxidation treatment (four saturation
      cycles) was applied to each wine. Average and initial oxygen consumption rates
      (OCR) were positively correlated to VRF/mA (vanilline reactive flavans/monomeric
      anthocyanins) and T/A ratios while OCRs were negatively related to the wine
      content in monomeric and total anthocyanins. The higher the A content was, the
      greater the loss of total and free anthocyanins. A significant lower production
      of polymeric pigments was detected in all pressed wines with respect to the
      correspondant free run one. A gradual decrease of tannin reactivity toward saliva
      proteins after the application of oxygen saturation cycles was detected. The
      results obtained in this experiment indicate that VRF/mA and T/A ratios are among
      the fundamental parameters to evaluate before choosing the antioxidant protection
      to be used and the right oxidation level to apply for a longer shelf-life of red
      wine.

PMID- 29600247
TI  - The Effects of Combinations of Cognitive Impairment and Pre-frailty on Adverse
      Outcomes from a Prospective Community-Based Cohort Study of Older Chinese People.
AB  - Objectives: To examine how various combinations of cognitive impairment (overall
      performance and specific domains) and pre-frailty predict risks of adverse
      outcomes; and to determine whether cognitive frailty may be defined as the
      combination of cognitive impairment and the presence of pre-frailty. Design:
      Community-based cohort study. Participants: Chinese men and women (n = 3,491)
      aged 65+ without dementia, Parkinson's disease and/or frailty at baseline.
      Measurements: Frailty was characterized using the Cardiovascular Health Study
      criteria. Overall cognitive impairment was defined by a Cantonese Mini-Mental
      Status Examination (CMMSE) total score (<21/24/27, depending on participants'
      educational levels); delayed recall impairment by a CMMSE delayed recall score
      (<3); and language and praxis impairment by a CMMSE language and praxis score
      (<9). Adverse outcomes included poor quality of life, physical limitation,
      increased cumulative hospital stay, and mortality. Results: Compared to those who
      were robust and cognitively intact at baseline, those who were robust but
      cognitively impaired were more likely to develop pre-frailty/frailty after 4
      years (P < 0.01). Compared to participants who were robust and cognitively intact
      at baseline, those who were pre-frail and with overall cognitive impairment had
      lower grip strength (P < 0.05), lower gait speed (P < 0.01), poorer lower limb
      strength (P < 0.01), and poorer delayed recall at year 4 [OR, 1.6; 95% confidence
      interval (CI), 1.2-2.3]. They were also associated with increased risks of poor
      quality of life (OR, 1.5; 95% CI, 1.1-2.2) and incident physical limitation at
      year 4 (OR, 1.8; 95% CI, 1.3-2.5), increased cumulative hospital stay at year 7
      (OR, 1.5; 95% CI, 1.1-2.1), and mortality over an average of 12 years (OR, 1.5;
      95% CI, 1.0-2.1) after adjustment for covariates. There was no significant
      difference in risks of adverse outcomes between participants who were pre-frail,
      with/without cognitive impairment at baseline. Similar results were obtained with
      delayed recall and language and praxis impairments. Conclusion: Robust and
      cognitively impaired participants had higher risks of becoming pre-frail/frail
      over 4 years compared with those with normal cognition. Cognitive impairment
      characterized by the CMMSE overall score or its individual domain score improved
      the predictive power of pre-frailty for poor quality of life, incident physical
      limitation, increased cumulative hospital stay, and mortality. Our findings
      support to the concept that cognitive frailty may be defined as the occurrence of
      both cognitive impairment and pre-frailty, not necessarily progressing to
      dementia.

PMID- 29600248
TI  - CD11b Activity Modulates Pathogenesis of Lupus Nephritis.
AB  - Lupus nephritis (LN) is a common complication of systemic lupus erythematosus
      (SLE) with unclear etiology and limited treatment options. Immune cell
      infiltration into the kidneys, a hallmark of LN, triggers tissue damage and
      proteinuria. CD11b, the alpha-chain of integrin receptor CD11b/CD18 (also known
      as alphaMbeta2, Mac-1, and CR3), is highly expressed on the surface of innate
      immune cells, including macrophages and neutrophils. Genetic variants in the
      human ITGAM gene, which encodes for CD11b, are strongly associated with
      susceptibility to SLE, LN, and other complications of SLE. CD11b modulates
      several key biological functions in innate immune cells, including cell adhesion,
      migration, and phagocytosis. CD11b also modulates other signaling pathways in
      these cells, such as the Toll-like receptor signaling pathways, that mediate
      generation of type I interferons, a key proinflammatory cytokine and circulating
      biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute
      to disease pathogenesis has not been completely established. Here, we provide an
      overview of CD11b modulated mechanisms and the functional consequences of the
      genetic variants that can drive disease pathogenesis. We also present recent
      insights from studies after pharmacological activation of CD11b. These studies
      offer novel mechanisms for development of therapeutics for LN, SLE and other
      autoimmune diseases.

PMID- 29600249
TI  - Human-Induced Pluripotent Stem Cells Manufactured Using a Current Good
      Manufacturing Practice-Compliant Process Differentiate Into Clinically Relevant
      Cells From Three Germ Layers.
AB  - The discovery of reprogramming and generation of human-induced pluripotent stem
      cells (iPSCs) has revolutionized the field of regenerative medicine and opened
      new opportunities in cell replacement therapies. While generation of iPSCs
      represents a significant breakthrough, the clinical relevance of iPSCs for cell
      based therapies requires generation of high-quality specialized cells through
      robust and reproducible directed differentiation protocols. We have recently
      reported manufacturing of human iPSC master cell banks (MCB) under current good
      manufacturing practices (cGMPs). Here, we describe the clinical potential of
      human iPSCs generated using this cGMP-compliant process by differentiating them
      into the cells from all three embryonic germ layers including ectoderm, endoderm,
      and mesoderm. Most importantly, we have shown that our iPSC manufacturing process
      and cell culture system is not biased toward a specific lineage. Following
      controlled induction into a specific differentiation lineage, specialized cells
      with morphological and cellular characteristics of neural stem cells, definitive
      endoderm, and cardiomyocytes were developed. We believe that these cGMP-compliant
      iPSCs have the potential to make various clinically relevant products suitable
      for cell therapy applications.

PMID- 29600250
TI  - Relaxase MobM Induces a Molecular Switch at Its Cognate Origin of Transfer.
AB  - The MOBV1 family of relaxases is broadly distributed in plasmids and other mobile
      genetic elements isolated from staphylococci, enterococci, and streptococci. The
      prototype of this family is protein MobM encoded by the streptococcal promiscuous
      plasmid pMV158. MobM cleaves the phosphodiester bond of a specific dinucleotide
      within the origin of transfer (oriT) to initiate conjugative transfer.
      Differently from other relaxases, MobM and probably other members of the family,
      cleaves its target single-stranded DNA through a histidine residue rather than
      the commonly used tyrosine. The oriT of the MOBV1 family differs from other well
      known conjugative systems since it has sequences with three inverted repeats,
      which were predicted to generate three mutually-exclusive hairpins on supercoiled
      DNA. In this work, such hypothesis was evaluated through footprinting experiments
      on supercoiled plasmid DNA. We have found a change in hairpin extrusion mediated
      by protein MobM. This conformational change involves a shift from the main
      hairpin generated on "naked" DNA to a different hairpin in which the nick site is
      positioned in a single-stranded configuration. Our results indicate that the
      oriTpMV158 acts as a molecular switch in which, depending on the inverted repeat
      recognized by MobM, pMV158 mobilization could be turned "on" or "off."

PMID- 29600252
TI  - Is a Single Fecal Microbiota Transplant a Promising Treatment for Recurrent
      Clostridium difficile Infection?
AB  - Clostridium difficile infection, a common hospital-associated infection, is a
      gastrointestinal illness that becomes recurrent in about 25% of infected
      patients. Fecal microbiota transplantation (FMT) is increasingly supported by
      clinical trials as an effective treatment for recurrent Clostridium difficile
      infection, but a number of questions remain about how it can be optimally
      performed. In this Perspective, we discuss controversies in FMT methodologies and
      reporting within randomized controlled trials, all of which may influence
      clinical outcomes in treated patients. Finally, we focus on the question of
      whether single vs multiple FMTs are necessary to achieve favorable outcomes for
      the treatment of recurrent Clostridium difficile infection, postulating on why
      there may be an association between number of FMTs and clinical effectiveness.

PMID- 29600251
TI  - General cognitive impairment as a risk factor for motor vehicle collision
      involvement: a prospective population-based study.
AB  - This study examined whether cognitive impairment and decline as assessed by a
      brief mental status screening test is associated with future crash risk in a
      cohort of older drivers. A three-year prospective study was conducted in a
      population-based sample of 2000 licensed drivers aged 70 years and older. At the
      baseline visit, cognitive impairment was defined as <24 on the Mini Mental State
      Exam (MMSE). Decline was defined as those with a 1-year change in MMSE scores in
      the lowest quartile (largest decrease). Motor vehicle collision involvement was
      obtained from the Alabama Department of Public Safety. Poisson regression was
      used to calculate crude and adjusted rate ratios (RR). There were 278 crashes
      during the follow-up period. Rates of crash involvement were higher for those
      with cognitive impairment (crude RR=2.33) compared to those without impairment at
      baseline; adjustment for potential confounders namely age and visual processing
      speed attenuated this relationship (adjusted RR=1.26, 95% CI 0.65-2.44). Drivers
      who experienced a pronounced decline in estimated MMSE scores in one year were
      1.64 (95% CI 1.04-2.57) times more likely to have a future at-fault crash
      compared to those whose scores did not decline. Evaluation of MMSE over time may
      provide important insight in an older driver's future risk of at-fault crash
      involvement.

PMID- 29600253
TI  - A Small RNA Isolation and Sequencing Protocol and Its Application to Assay CRISPR
      RNA Biogenesis in Bacteria.
AB  - Next generation high-throughput sequencing has enabled sensitive and unambiguous
      analysis of RNA populations in cells. Here, we describe a method for isolation
      and strand-specific sequencing of small RNA pools from bacteria that can be
      multiplexed to accommodate multiple biological samples in a single experiment.
      Small RNAs are isolated by polyacrylamide gel electrophoresis and treated with T4
      polynucleotide kinase. This allows for 3' adapter ligation to CRISPR RNAs, which
      don't have pre-existing 3'-OH ends. Pre-adenylated adapters are then ligated
      using T4 RNA ligase 1 in the absence of ATP and with a high concentration of
      polyethylene glycol (PEG). The 3' capture step enables precise determination of
      the 3' ends of diverse RNA molecules. Additionally, a random hexamer in the
      ligated adapter helps control for potential downstream amplification bias.
      Following reverse-transcription, the cDNA product is circularized and libraries
      are prepared by PCR. We show that the amplified library need not be visible by
      gel electrophoresis for efficient sequencing of the desired product. Using this
      method, we routinely prepare RNA sequencing libraries from minute amounts of
      purified small RNA. This protocol is tailored to assay for CRISPR RNA biogenesis
      in bacteria through sequencing of mature CRISPR RNAs, but can be used to sequence
      diverse classes of small RNAs. We also provide a fully worked example of our data
      processing pipeline, with instructions for running the provided scripts.

PMID- 29600254
TI  - Anesthesiology Residency Curriculum and Implementation of a Perioperative
      Surgical Home Curriculum: A Survey Study.
AB  - Background: The perioperative surgical home (PSH) is a physician-led,
      interdisciplinary, and patient-centered model of perioperative care that focuses
      on patient outcomes and comprehensive care management. Many studies to date have
      looked at the clinical implementation of varied PSH models with promising results
      discussed. There are no studies directly examining concrete plans for the various
      Accreditation Council for Graduate Medical Education (ACGME) anesthesiology
      residency programs to implement augmented PSH training into curricula. The aim of
      this survey study was to better assess current residency training in PSH.
      Methods: An 18-question survey developed by a team of research personnel familiar
      with the PSH was sent to all ACGME accredited anesthesiology training programs in
      the United States. Responses were quantified, and construct and external validity
      of the survey tool examined. Results: 41% of the programs responded. 89% (95% CI
      78-96%) of programs reported moderate or better understanding of the PSH. 34% (21
      47%) had incorporated additional PSH training in the previous three years, and
      32% (with no significant correlation to the previous group) had plans to
      integrate more training in the next 3 years. Conclusions: Overall, the surveyed
      program directors voiced understanding of the value of the PSH model in patient
      care but remained hesitant to incorporate training specific to PSH into the
      anesthesiology residency curricula.

PMID- 29600255
TI  - Emergency Manuals Improved Novice Physician Performance During Simulated ICU
      Emergencies.
AB  - Background: Emergency manuals, which are safety essentials in non-medical high
      reliability organizations (e.g., aviation), have recently gained acceptance in
      critical medical environments. Of the existing emergency manuals in
      anesthesiology, most are geared towards intraoperative settings. Additionally,
      most evidence supporting their efficacy focuses on the study of physicians with
      at least some meaningful experience as a physician. Our aim was to evaluate
      whether an emergency manual would improve the performance of novice physicians
      (post-graduate year [PGY] 1 or first year resident) in managing a critical event
      in the intensive care unit (ICU). Methods: PGY1 interns (n=41) were assessed on
      the management of a simulated critical event (unstable bradycardia) in the ICU.
      Participants underwent a group allocation process to either a control group
      (n=18) or an intervention group (emergency manual provided, n=23). The number of
      successfully executed treatment and diagnostic interventions completed was
      evaluated over a ten minute (600 seconds) simulation for each participant.
      Results: The participants using the emergency manual averaged 9.9/12 (83%)
      interventions, compared to an average of 7.1/12 (59%) interventions (p < 0.01) in
      the control group. Conclusions: The use of an emergency manual was associated
      with a significant improvement in critical event management by individual novice
      physicians in a simulated ICU patient (23% average increase).

PMID- 29600256
TI  - Fellowships Represent a Logical Target for Cultivating Research in Academic
      Anesthesiology.
AB  - Background: The need for greater emphasis on research contributions in academic
      anesthesiology has been widely recognized in recent years. Some propose
      increasing integration of research, including dedicated research time, into ACGME
      requirements for residency and fellowship training experiences. The h-index, an
      effective measure of research productivity that takes into account relevance and
      impact of an author's contributions on discourse within a field, was used to
      examine whether there are differences in research productivity between non
      fellowship and fellowship-trained faculty in academic anesthesiology departments.
      This bibliometric was further used to examine differences in subspecialties, and
      other specialties of medicine. Methods: Research productivity, as measured by the
      h-index, was examined using the Scopus database for 508 academic
      Anesthesiologists practicing in the various subspecialties. Results: There was no
      statistical difference in research productivity, as measured by the h-index,
      between non-fellowship and fellowship-trained academic anesthesiologists (2.98+
      0.32 vs. 2.88+-0.31). Critical care anesthesiologists had the highest h-indices
      (5.78+-1.11), while regional anesthesia and pain medicine practitioners had the
      lowest values (1.18+-0.32). Unlike in anesthesiology, a sample of physicians from
      other specialties revealed a statistical difference in h-index between non
      fellowship and fellowship-trained physicians. Conclusions: Scholarly
      productivity, as measured by the h-index was similar for fellowship and non
      fellowship trained anesthesiologists.

PMID- 29600257
TI  - Developing a Comprehensive Perioperative Education Curriculum for Internal
      Medicine Residency Training.
AB  - Background: Patients undergoing surgery are becoming increasingly complex and
      internists are becoming more involved in their perioperative care. Therefore, new
      requirements from the ACGME/ABIM necessitate education in this area. We aim to
      discuss how our institution adapted a perioperative curriculum to fill this need.
      Methods: Perioperative education is primarily given to the residents during their
      one month rotation through the General Internal Medicine Consult Service
      rotation. This is an inpatient rotation that provides perioperative expertise to
      surgical teams, medicine consultation to medical subspecialty teams, and
      outpatient preoperative evaluations. Results: Our implementation complies with
      ACGME/ABIM requirements and ensures that the educational and clinical needs of
      our institution are met. Conclusions: Developing a new curriculum can be
      daunting. We hope that this explanation of our approach will aid others who are
      working to develop an effective perioperative curriculum at their institutions.

PMID- 29600258
TI  - Nicotine and Anatabine Exposure from Very Low Nicotine Content Cigarettes.
AB  - Objectives: Research using very low nicotine content (VLNC) cigarettes has shown
      that participants underreport use of non-study cigarettes. Biomarkers of nicotine
      exposure could be used to verify compliance with VLNC cigarettes. This study
      aimed to characterize biomarkers of exposure when participants exclusively use
      VLNC cigarettes. Methods: 23 participants stayed in a hotel that permitted
      smoking for 5 days and 4 nights. They were provided 2 packs of VLNC cigarettes
      each day (0.4 mg of nicotine/g of tobacco; Spectrum cigarettes) and did not have
      access to other tobacco products. 24-hour urine samples were collected to assess
      exposure to nicotine and anatabine. Results: After 4 days of exclusive use, the
      geometric means for urinary total cotinine, total nicotine equivalents (TNE), and
      anatabine were 1.13 nmol/ml (92% reduction), 3.17 nmol/ml (94% reduction) and
      0.0031 nmol/ml (93% reduction). The population estimates of the 95th percentile
      of cotinine, TNE, and anatabine levels were 2.69, 6.41, and 0.0099 nmol/ml,
      respectively. Conclusions: Study participants exclusively smoking 0.4 mg/g
      Spectrum cigarettes are unlikely to have biomarker values above these levels. The
      data presented here will be valuable to researchers conducting research on use of
      VLNC cigarettes.

PMID- 29600259
TI  - The Most Appropriate Reconstruction Method Following Giant Cell Tumor Curettage:
      A Biomechanical Approach.

PMID- 29600261
TI  - Total Knee Replacement Sizing: Shoe Size Is a Better Predictor for Implant Size
      than Body Height.
AB  - Background: Various sizes of implants need to be available during surgery. The
      purpose of this paper is to compare body height and shoe size with implant sizes
      in patients who underwent total knee replacement surgery to see which biomarker
      is a better predictor for preoperative planning to determine implant size.
      Methods: A total of 100 knees, belonging to 50 females and 50 males, were
      observed. Participants' body height and shoe size were collected and correlated
      to implant sizes of a current, frequently used, standard total knee replacement
      (TKR) implant. The femoral anteroposterior and mediolateral width and the tibial
      anteroposterior and mediolateral width were correlated with height and shoe size.
      Results: The correlation between shoe size and the four knee implant dimensions,
      femoral AP, ML, and tibial AP and ML were higher than the correlations between
      height and the same four dimensions. Conclusion: The results indicated that shoe
      size is a better predictor of component dimensions than is body height.Level of
      evidence: III.

PMID- 29600262
TI  - The Stabilising Effect of the Anterior Oblique Ligament to Prevent Directional
      Subluxation at the Trapeziometacarpal Joint of the Thumb: A Biomechanical
      Cadaveric Study.
AB  - Background: The trapeziometacarpal joint (TMCJ) is inherently unstable, relying
      on ligament restraint to prevent subluxation. Subluxation of the thumb in a
      dorsoradial direction is often observed in clinical practice, either after acute
      ligament injury or more commonly with osteoarthritis (OA). This subluxation
      follows loss of function of trapeziometacarpal ligaments that stabilise this
      joint, resisting the deforming force of abductor pollicis longus (APL). The exact
      ligaments that stabilise and prevent the thumb from the pull of APL causing
      dorsoradial subluxation remain unknown, although the anterior oblique ligament
      (AOL) has been implicated. The aim of this study was to measure the direction of
      subluxation resisted by the AOL. Methods: In this study we used cadaveric limbs
      and custom made biomechanical testing to measure the influence AOL has in
      stabilising the thumb against subluxation in three planes: radial, dorsal and
      dorsoradial. Three fresh frozen hands were dissected to expose the TMCJ, leaving
      all ligaments, capsule and APL attachment in place. The force required to create
      a displacement of 5mm between the first metacarpal and the trapezium in these
      three planes was measured before and after AOL division. Results: The average
      force to displace in the dorsoradial plane prior to division was 6.68N, and a
      statistically significant reduction to 1.15N (P<0.001) was found after division
      of the AOL. A statistically significant increase in force (P<0.001) from 2.89N to
      4.04N was seen in the radial plane, while no change was seen dorsally (P=0.98),
      with average forces of 2.74N and 2.62N found pre and post division. Conclusion:
      There is clinical significance in reporting quantifiable data in this field, as
      subluxation of the thumb is often seen with OA. The results of our study provide
      support for surgical reconstruction of the AOL as the primary surgical stabilizer
      against dorsoradial subluxation of the thumb.Level of evidence: III.

PMID- 29600260
TI  - Current Concepts in Scaffolding for Bone Tissue Engineering.
AB  - Bone disorders are of significant worry due to their increased prevalence in the
      median age. Scaffold-based bone tissue engineering holds great promise for the
      future of osseous defects therapies. Porous composite materials and functional
      coatings for metallic implants have been introduced in next generation of
      orthopedic medicine for tissue engineering. While osteoconductive materials such
      as hydroxyapatite and tricalcium phosphate ceramics as well as some biodegradable
      polymers are suggested, much interest has recently focused on the use of
      osteoinductive materials like demineralized bone matrix or bone derivatives.
      However, physiochemical modifications in terms of porosity, mechanical strength,
      cell adhesion, biocompatibility, cell proliferation, mineralization and
      osteogenic differentiation are required. This paper reviews studies on bone
      tissue engineering from the biomaterial point of view in scaffolding. Level of
      evidence: I.

PMID- 29600263
TI  - Combination of High Tibial Osteotomy and Autologous Bone Marrow Derived Cell
      Implantation in Early Osteoarthritis of Knee: A Preliminary Study.
AB  - Background: High tibial osteotomy (HTO) is a recommended treatment for medial
      compartment knee osteoarthritis. Newer cartilage regenerative procedures may add
      benefits to the results of HTO. In this prospective study we have investigated
      the safety and also results of HTO associated with autologous bone marrow derived
      cells (BMDC) implantation in relatively young and middle aged active individuals
      with early osteoarthritis of the knee. Methods: A total of 24 patients (mean age
      of 47.9 years) with varus knee and symptomatic medial compartment osteoarthritis
      were treated with medial opening-wedge high tibial osteotomy in conjunction with
      implantation of bone marrow derived cells into the chondral lesions. The clinical
      outcomes were assessed by IKDC, KOOS, VAS, and Tegner scores. The radiographic
      studies were performed preoperatively and at follow-ups. Results: No major
      complications were seen during the operations and postoperative follow-ups. All
      clinical scores were significantly improved for the IKDC score (from 32.7+/-15 to
      64+/-21) (P<0.005), KOOS score (from30+/-11 to 68+/-19) (P<0.005), VAS (from 7.5
      to 3) and Tegner score (from 1.2 to 2.1) (P<0.004). Conclusion: HTO in
      conjunction with BMDC implantation is a safe and feasible treatment and is
      associated with good results in short term follow up for early medial compartment
      osteoarthritis in varus knees.Level of evidence: IV.

PMID- 29600264
TI  - Reliability and Validity of the Swiss Spinal Stenosis Questionnaire for Iranian
      Patients with Lumbar Spinal Stenosis.
AB  - Background: The purpose of this study was validation of the Persian translation
      of the Swiss Spinal Stenosis Questionnaire in order to be used by Iranian
      researchers. Methods: A total of 104 patients with spinal stenosis diagnosis, who
      were candidates for operative treatment were entered into the study. The patients
      completed the translated questionnaire in the 1st and the 7th days of admission
      and 6 months after surgery. Visual analogue scale was used to determine the
      severity of the pain in the1st day and the 6th month. Discriminant validity,
      convergent validity, test-retest reliability, internal consistency, ability to
      detect changes and sensitivity to clinical changes were assessed for the
      statistical purposes. Results: Cronbach's alpha was more than 0.9 for all the
      items. ICC was about 0.9 for all the items. For symptoms, physical and total
      items, Cronbach's alpha was 0.942, 0.957, 0.926 and Intraclass correlation were
      0.891, 0.918, 0.862, respectively. Paired t-test was significantly different
      between the 1st day and the 6th month questionnaire. There was a positive
      correlation either between the first VAS and the 1st day questionnaire (1st day
      Q) (r=0.892, P=0.000) or between the 6th month VAS and 6th month Q (r=0.940,
      P=0.000). The Pearson's correlation between the difference of the total scores of
      the 1st day and the 6th month and satisfaction score after surgery showed
      negative correlation (r= -0.746, P=0.000). The effect size was 2.55. Conclusion:
      The Iranian version of the Swiss Spinal Stenosis has excellent internal
      consistency, excellent reliability, good ability to alter with changes,
      especially parallel with clinical improvement, excellent ability to detect
      changes, and well either convergent or discriminant validity.Level of evidence:
      II.

PMID- 29600265
TI  - Comparison of Clinical Results between Patellar Resurfacing and Non-resurfacing
      in Total Knee Arthroplasty: A Short Term Evaluation.
AB  - Background: There is no difference in the functional outcomes 6 months after
      total knee arthroplasty (TKA) for knee osteoarthritis between patellar
      resurfacing and non-resurfacing. Thus, we have performed this study to compare
      the short-term clinical outcomes of TKA performed with and without the patella
      resurfacing. Methods: A total of 50 patients with osteoarthritis of the knee
      (OAK) were randomized to receive patellar resurfacing (n=24; resurfaced group) or
      to retain their native patella (n=26; non-resurfaced group) based on envelope
      selection and provided informed consent. Disease specific outcomes including Knee
      Society Score (KSS), Knee Society Function Score (KSKS-F), Kujala Anterior Knee
      Pain Scale (AKPS), Western Ontario and McMaster Universities Arthritis Index
      (WOMAC), Short Form 36 (SF-36), and functional patella-related activities were
      measured within six months of follow-up. Results: There was no significant
      difference between the resurfaced and non-resurfaced groups in pre and post
      operative improvement of range of motion (ROM) (P=0.421), KSS (P=0.782, P=0.553),
      KSKS-F (P=0.241, P=0.293), AKPS (P=0.128, P=0.443), WOMAC (P=0.700, P=0.282), and
      pain scores (P=0.120, P=0.508). There was no difference in ROM between resurfaced
      and non-resurfaced group pre (15.24 degrees  and 15.45 degrees ) and post
      operative (18.48 degrees  and 18.74). No side effects related to patella was
      observed in any of the groups. Revision was required in none of the participants.
      Conclusion: The results showed no significant difference between patellar
      resurfacing and non-resurfacing in TKA for all outcome measures in a short
      term.Level of evidence: I.

PMID- 29600266
TI  - Clinical Outcome of Anatomical Transportal Arthroscopic Anterior Cruciate
      Ligament Reconstruction with Hamstring Tendon Autograft.
AB  - Background: Good clinical outcome and return to sport and daily functions after
      anatomical arthroscopic anterior cruciate ligament (ACL) reconstruction is goal
      standard in this surgery. but to date, there are different challenging issues
      between orthopedic surgeons regarding graft selection and surgical techniques.
      Methods: We retrospectively reviewed the patients who underwent anatomical
      arthroscopic one bundle ACL reconstruction with quadruple hamstring tendon
      autograft from 2010 to 2016 in our orthopedic sport medicine center. Eighty-two
      eligible patients (82 knees) who had met our inclusion criteria were examined in
      terms of knee stability by clinical examinations and KT 2000 arthrometer and -
      also were evaluated regarding variables related to their health and knee status
      with a mean 48months follow-up. Results: Seventy-seven patients (93.9%) were male
      and the other 5 cases (6.1%) were female. The mean age was 33 +/- 8.06 years old
      at the time of surgery and mean BMI amount was 26.81 +/- 3.72. 78 patients (95%)
      returned to pre-injury sport activity level after ACL reconstruction and two
      patients (2.4%) had re-rupture. 63 patients (76.8%) had negative anterior drawer
      and 67patients (81.8%) negative lachman tests respectively. 10 patients (13%)
      were found to have positive pivot shift tests which was correlated with pain and
      a less KOOS scores with a significant difference (P= 0.03). 72 patients (87%) had
      negative tests in active and 70 (85.4%) had less than 3 mm side to side
      difference in manual testing by KT2000. Final KOOS score was 70.87 +/- 19.76.
      Mean Lysholm score was 90 +/- 4.77. Mean International Knee Documentation
      Committee (IKDC) score of this study was 85 +/- 14.11.Patients who had
      concomitant partial meniscectomy had significantly lower IKDC scores
      (P<0.01).Mean kujala score was 79 +/- 3.07. Conclusion: The use of quadrupled
      hamstring tendon autograft besides the most important part of the treatment which
      is the surgical technique would yield to excellent results in ACL reconstruction
      both subjectively and objectively. In addition, patient selection and surgeon's
      experience should be considered in determining the treatment plan for the
      patients.Level of evidence: IV.

PMID- 29600267
TI  - Epineural Sleeve Reconstruction Technique for Median Nerve Complete Transection.
AB  - In microsurgical nerve repair, the epineural sleeve technique can be used to
      bridge short nerve defects and to cover the coaptation site with the epineurium
      of the nerve stump. The epineurium serves as a mechanical aid to reduce gap size,
      and increase repair strength, effectively assisting nerve regeneration. This
      article presents a 32-year-old patient who experienced complete transection of
      the median nerve at the distal forearm, which was treated with the epineural
      sleeve graft reconstruction technique. Nerve regeneration was followed-up for 18
      months and evaluated with the Rosen and Lundborg scoring system. The final
      outcome was excellent; at the last follow-up, the patient experienced complete
      sensory and motor function of the median nerve. Level of evidence: V.

PMID- 29600268
TI  - Healing of Complete Tear of the Anterior Talofibular Ligament and Early Ankle
      Stabilization after Autologous Platelet Rich Plasma: a Case Report and Literature
      Review.
AB  - Lateral Ankle sprain (LAS) is a common sports injury associated with recurrent
      ankle sprain, chronic ankle instability (CAI) and post-traumatic ankle
      osteoarthritis (PTOA). Platelet Rich Plasma (PRP) has been increasingly used for
      herapeutic applications in sports-related injuries, and is thought to stimulate
      tissue healing. We reported a case of LAS with complete tear of anterior
      talofibular ligament, which showed complete healing of ligament and early ankle
      stabilization after PRP. The healing is supported by dynamic ultrasound images
      and magnetic resonance imaging. We therefore proposed that PRP may serve as an
      alternative non-surgical treatment option in LAS in future research, with the
      potential to prevent the development of CAI and PTOA. Level of evidence: IV.

PMID- 29600269
TI  - Acute Combined Median and Radial Nerve Palsies after Distal Humeral Shaft
      Fracture.
AB  - We report a case of a 29-year-old man who presented with a distal humeral shaft
      fracture sustained by blunt trauma. Physical examination and nerve conduction
      study were consistent with injury to the median and radial nerves proximal to the
      elbow. The patient underwent open reduction and internal fixation of the humeral
      shaft fracture with neurolysis of the median and radial nerves. Repeat
      electromyography at 6 months postoperatively showed recruitment of motor units in
      all muscles sampled, in keeping with clinical improvement. At 16 months follow
      up, the patient was full strength in all muscle groups, was back to all
      activities with no restrictions, and was discharged from follow-up. Our case
      describes clinical improvement after surgical intervention in a patient with
      combined median and radial nerve palsies following distal humeral shaft fracture.
      Level of evidence: V.

PMID- 29600270
TI  - Intrapelvic Protrusion of a Broken Guide Wire Fragment during Fixation of a
      Femoral Neck Fracture.

PMID- 29600271
TI  - Oxygen isotopic evidence for accretion of Earth's water before a high-energy Moon
      forming giant impact.
AB  - The Earth-Moon system likely formed as a result of a collision between two large
      planetary objects. Debate about their relative masses, the impact energy
      involved, and the extent of isotopic homogenization continues. We present the
      results of a high-precision oxygen isotope study of an extensive suite of lunar
      and terrestrial samples. We demonstrate that lunar rocks and terrestrial basalts
      show a 3 to 4 ppm (parts per million), statistically resolvable, difference in
      Delta17O. Taking aubrite meteorites as a candidate impactor material, we show
      that the giant impact scenario involved nearly complete mixing between the target
      and impactor. Alternatively, the degree of similarity between the Delta17O values
      of the impactor and the proto-Earth must have been significantly closer than that
      between Earth and aubrites. If the Earth-Moon system evolved from an initially
      highly vaporized and isotopically homogenized state, as indicated by recent
      dynamical models, then the terrestrial basalt-lunar oxygen isotope difference
      detected by our study may be a reflection of post-giant impact additions to
      Earth. On the basis of this assumption, our data indicate that post-giant impact
      additions to Earth could have contributed between 5 and 30% of Earth's water,
      depending on global water estimates. Consequently, our data indicate that the
      bulk of Earth's water was accreted before the giant impact and not later, as
      often proposed.

PMID- 29600272
TI  - A climate-associated multispecies cryptic cline in the northwest Atlantic.
AB  - The spatial genetic structure of most species in the open marine environment
      remains largely unresolved. This information gap creates uncertainty in the
      sustainable management, recovery, and associated resilience of marine communities
      and our capacity to extrapolate beyond the few species for which such information
      exists. We document a previously unidentified multispecies biogeographic break
      aligned with a steep climatic gradient and driven by seasonal temperature minima
      in the northwest Atlantic. The coherence of this genetic break across our five
      study species with contrasting life histories suggests a pervasive
      macroecological phenomenon. The integration of this genetic structure with
      habitat suitability models and climate forecasts predicts significant variation
      in northward distributional shifts among populations and availability of suitable
      habitat in future oceans. The results of our integrated approach provide new
      perspective on how cryptic intraspecific diversity associated with climatic
      variation influences species and community response to climate change beyond
      simple poleward shifts.

PMID- 29600273
TI  - The photoreactive free radical in eumelanin.
AB  - Melanin is the primary photoprotecting pigment in humans as well as being
      implicated in the development of deadly melanoma. The material also conducts
      electricity and has thus become a bioelectronic model for proton-to-electron
      transduction. Central to these phenomena are its spin properties-notably two
      linked species derived from carbon-centered and semiquinone radicals. Using a
      novel in situ photoinduced electron paramagnetic resonance technique with
      simultaneous electrical measurements, we have elucidated for the first time the
      distinct photoreactivity of the two different radical species. We find that the
      production of the semiquinone is light- and water-driven, explaining the
      electrical properties and revealing biologically relevant photoreactivity.

PMID- 29600274
TI  - WDR45 mutations may cause a MECP2 mutation-negative Rett syndrome phenotype.

PMID- 29600275
TI  - Ataxia-telangiectasia: A new remitting form with a peculiar transcriptome
      signature.
AB  - Objective: Ataxia-telangiectasia (AT) is a rare, severe, and ineluctably
      progressive multisystemic neurodegenerative disease. Variant AT phenotypes have
      been described in patients with mild- and late-onset neurologic deterioration and
      atypical features (dystonia and myoclonus). We report on the clinical
      characteristics and transcriptome profile of patients with a typical AT
      presentation and genotype who experienced an unexpected favorable course.
      Methods: A 24-year-old woman developed, by the age of 3 years, all the classic
      symptoms of AT associated with increased alpha-fetoprotein levels, a compound AT
      mutated (ATM) genotype with an inframe deletion c.2250G>A (p.Glu709_Lys750del42)
      and a missense mutation c.8122G>A (p.Asp2708Gln), and no residual ATM protein
      expression. By the age of 12 years, ataxia slowly disappeared, and a very mild
      choreic disorder was the only neurologic feature in adulthood. Brain MRI was
      normal. The blood transcriptome profile was assessed and compared with that of
      healthy controls and patients with the classic AT phenotype. Results: The
      atypical clinical course of the patient was associated with a transitional
      transcriptome profile: while 90% of transcripts were expressed as in patients
      with the classic AT presentation, 10% of transcripts were expressed as in healthy
      controls. Conclusions: The unexpected mild clinical outcome and transcriptome
      profile of this patient with AT suggest the existence of individual resilience to
      the altered ATM synthesis. Because of their possible prognostic and therapeutic
      implications, the identification of modifier factors affecting the phenotype
      would deserve further studies.

PMID- 29600276
TI  - Diagnostic odyssey of patients with mitochondrial disease: Results of a survey.
AB  - Objective: To document the complex "diagnostic odyssey" of patients with
      mitochondrial disease. Methods: We analyzed data from 210 Rare Diseases Clinical
      Research Network Contact Registry participants who were patients with a
      biochemical deficiency or self-reported diagnosis of mitochondrial disease, or
      their caregivers. Results: Participants saw an average of 8.19 clinicians (SD
      8.0, median 5). The first clinician consulted about symptoms was typically a
      primary care physician (56.7%), although 35.2% of participants initially sought a
      specialist. Of note, 55.2% of participants received their diagnosis from a
      neurologist, 18.2% from a clinical geneticist, and 11.8% from a metabolic disease
      specialist. A majority of the participants (54.6%) received 1 or more
      nonmitochondrial diagnoses before their final mitochondrial diagnosis. In their
      pursuit of a diagnosis, 84.8% of participants received blood tests, 71% a muscle
      biopsy, 60.5% MRI, and 38.6% urine organic acids. In addition, 39.5% of the
      participants underwent mitochondrial DNA sequencing, 19% sequencing of nuclear
      gene(s), and 11.4% whole-exome sequencing. Conclusions: The diagnostic odyssey of
      patients with mitochondrial disease is complex and burdensome. It features
      multiple consultations and tests, and, often, conflicting diagnoses. These
      reflect disease variety, diagnostic uncertainty, and clinician unfamiliarity. The
      current survey provides an important benchmark. Its replication at appropriate
      intervals will assist in tracking changes that may accompany increased popularity
      of exome testing, more rigorous diagnostic criteria, increased patient reported
      outcome activity, and trials for promising therapies.

PMID- 29600277
TI  - Malign Differentiation of a Large Buschke Loewenstein Tumor in Penis.
AB  - Buschke-Loewenstein tumor (BLT) is a giant condyloma acuminatum which is very
      rare and commonly affects the anogenital region. The malignant transformation and
      localization in penis is very rare. This article aims to present a case with BLT
      with malignant transformation in penis. A 59-year-old male patient was referred,
      who has have been suffering from a cauliflower-like lesion in the penis for 8
      years. Biopsies revealed a BLT with malignant transformation. The lesion was
      excised largely and reconstructed with local flaps and skin grafts. Defined by
      Buschke and Loewenstein in 1925, giant condyloma acuminatum is a rare and
      important disorder because of the sexually transmitting capability.

PMID- 29600278
TI  - Shifts in the Gut Metabolome and Clostridium difficile Transcriptome throughout
      Colonization and Infection in a Mouse Model.
AB  - Antibiotics alter the gut microbiota and decrease resistance to Clostridium
      difficile colonization; however, the mechanisms driving colonization resistance
      are not well understood. Loss of resistance to C. difficile colonization due to
      antibiotic treatment is associated with alterations in the gut metabolome,
      specifically, with increases in levels of nutrients that C. difficile can utilize
      for growth in vitro. To define the nutrients that C. difficile requires for
      colonization and pathogenesis in vivo, we used a combination of mass spectrometry
      and RNA sequencing (RNA Seq) to model the gut metabolome and C. difficile
      transcriptome throughout an acute infection in a mouse model at the following
      time points: 0, 12, 24, and 30 h. We also performed multivariate-based
      integration of the omics data to define the signatures that were most important
      throughout colonization and infection. Here we show that amino acids, in
      particular, proline and branched-chain amino acids, and carbohydrates decrease in
      abundance over time in the mouse cecum and that C. difficile gene expression is
      consistent with their utilization in vivo. This was also reinforced by the
      multivariate-based integration of the omics data where we were able to
      discriminate the metabolites and transcripts that support C. difficile physiology
      between the different time points throughout colonization and infection. This
      report illustrates how important the availability of amino acids and other
      nutrients is for the initial stages of C. difficile colonization and progression
      of disease. Future studies identifying the source of the nutrients and
      engineering bacteria capable of outcompeting C. difficile in the gut will be
      important for developing new targeted bacterial therapeutics. IMPORTANCE
      Clostridium difficile is a bacterial pathogen of global significance that is a
      major cause of antibiotic-associated diarrhea. Antibiotics deplete the indigenous
      gut microbiota and change the metabolic environment in the gut to one favoring C.
      difficile growth. Here we used metabolomics and transcriptomics to define the gut
      environment after antibiotics and during the initial stages of C. difficile
      colonization and infection. We show that amino acids, in particular, proline and
      branched-chain amino acids, and carbohydrates decrease in abundance over time and
      that C. difficile gene expression is consistent with their utilization by the
      bacterium in vivo. We employed an integrated approach to analyze the metabolome
      and transcriptome to identify associations between metabolites and transcripts.
      This highlighted the importance of key nutrients in the early stages of
      colonization, and the data provide a rationale for the development of therapies
      based on the use of bacteria that specifically compete for nutrients that are
      essential for C. difficile colonization and disease.

PMID- 29600279
TI  - Intracellular Trafficking and Persistence of Acinetobacter baumannii Requires
      Transcription Factor EB.
AB  - Acinetobacter baumannii is a significant human pathogen associated with hospital
      acquired infections. While adhesion, an initial and important step in A.
      baumannii infection, is well characterized, the intracellular trafficking of this
      pathogen inside host cells remains poorly studied. Here, we demonstrate that
      transcription factor EB (TFEB) is activated after A. baumannii infection of human
      lung epithelial cells (A549). We also show that TFEB is required for the invasion
      and persistence inside A549 cells. Consequently, lysosomal biogenesis and
      autophagy activation were observed after TFEB activation which could increase the
      death of A549 cells. In addition, using the Caenorhabditis elegans infection
      model by A. baumannii, the TFEB orthologue HLH-30 was required for survival of
      the nematode to infection, although nuclear translocation of HLH-30 was not
      required. These results identify TFEB as a conserved key factor in the
      pathogenesis of A. baumannii. IMPORTANCE Adhesion is an initial and important
      step in Acinetobacter baumannii infections. However, the mechanism of entrance
      and persistence inside host cells is unclear and remains to be understood. In
      this study, we report that, in addition to its known role in host defense against
      Gram-positive bacterial infection, TFEB also plays an important role in the
      intracellular trafficking of A. baumannii in host cells. TFEB was activated
      shortly after A. baumannii infection and is required for its persistence within
      host cells. Additionally, using the C. elegans infection model by A. baumannii,
      the TFEB orthologue HLH-30 was required for survival of the nematode to
      infection, although nuclear translocation of HLH-30 was not required.

PMID- 29600280
TI  - Reproductive System Symbiotic Bacteria Are Conserved between Two Distinct
      Populations of Euprymna scolopes from Oahu, Hawaii.
AB  - Female Hawaiian bobtail squid, Euprymna scolopes, harbor a symbiotic bacterial
      community in a reproductive organ, the accessory nidamental gland (ANG). This
      community is known to be stable over several generations of wild-caught bobtail
      squid but has, to date, been examined for only one population in Maunalua Bay,
      Oahu, HI. This study assessed the ANG and corresponding egg jelly coat (JC)
      bacterial communities for another genetically isolated host population from
      Kaneohe Bay, Oahu, HI, using 16S amplicon sequencing. The bacterial communities
      from the ANGs and JCs of the two populations were found to be similar in
      richness, evenness, phylogenetic diversity, and overall community composition.
      However, the Kaneohe Bay samples formed their own subset within the Maunalua Bay
      ANG/JC community. An Alteromonadaceae genus, BD2-13, was significantly higher in
      relative abundance in the Kaneohe Bay population, and several Alphaproteobacteria
      taxa also shifted in relative abundance between the two groups. This variation
      could be due to local adaptation to differing environmental challenges, to
      localized variability, or to functional redundancy among the ANG taxa. The
      overall stability of the community between the populations further supports a
      crucial functional role that has been hypothesized for this symbiosis. IMPORTANCE
      In this study, we examined the reproductive ANG symbiosis found in two
      genetically isolated populations of the Hawaiian bobtail squid, Euprymna
      scolopes. The stability of the community reported here provides support for the
      hypothesis that this symbiosis is under strong selective pressure, while the
      observed differences suggest that some level of local adaptation may have
      occurred. These two host populations are frequently used interchangeably as
      source populations for research. Euprymna scolopes is an important model organism
      and offers the opportunity to examine the interplay between a binary and a
      consortial symbiosis in a single model host. Understanding the inherent natural
      variability of this association will aid in our understanding of the
      conservation, function, transmission, and development of the ANG symbiosis.

PMID- 29600281
TI  - Construction and Use of a Recyclable Marker To Examine the Role of Major
      Facilitator Superfamily Protein Members in Candida glabrata Drug Resistance
      Phenotypes.
AB  - Candida glabrata is the second most common species causing candidiasis. C.
      glabrata can also readily acquire resistance to azole drugs, complicating its
      treatment. Here we add to the collection of disruption markers to aid in genetic
      analysis of this yeast. This new construct is marked with a nourseothricin
      resistance cassette that produces an estrogen-activated form of Cre recombinase
      in a methionine-regulated manner. This allows eviction and reuse of this cassette
      in a facile manner. Using this new disruption marker, we have constructed a
      series of strains lacking different members of the major facilitator superfamily
      (MFS) of membrane transporter proteins. The presence of 15 MFS proteins that may
      contribute to drug resistance in C. glabrata placed a premium on development of a
      marker that could easily be reused to construct multiple gene-disrupted strains.
      Employing this recyclable marker, we found that loss of the MFS transporter
      encoding gene FLR1 caused a dramatic increase in diamide resistance (as seen
      before), and deletion of two other MFS-encoding genes did not influence this
      phenotype. Interestingly, loss of FLR1 led to an increase in levels of oxidized
      glutathione, suggesting a possible molecular explanation for this enhanced
      oxidant sensitivity. We also found that while overproduction of the transcription
      factor Yap1 could suppress the fluconazole sensitivity caused by loss of the
      important ATP-binding cassette transporter protein Cdr1, this required the
      presence of FLR1. IMPORTANCE Export of drugs is a problem for chemotherapy of
      infectious organisms. A class of membrane proteins called the major facilitator
      superfamily contains a large number of proteins that often elevate drug
      resistance when overproduced but do not impact this phenotype when the gene is
      removed. We wondered if this absence of a phenotype for a disruption allele might
      be due to the redundancy of this group of membrane proteins. We describe the
      production of an easy-to-use recyclable marker cassette that will allow
      construction of strains lacking multiple members of the MFS family of transporter
      proteins.

PMID- 29600282
TI  - Investigating Colonization of the Healthy Adult Gastrointestinal Tract by Fungi.
AB  - A wide diversity of fungi have been detected in the human gastrointestinal (GI)
      tract with the potential to provide or influence important functions. However,
      many of the fungi most commonly detected in stool samples are also present in
      food or the oral cavity. Therefore, to recognize which gut fungi are likely to
      have a sustained influence on human health, there is a need to separate transient
      members of the GI tract from true colonizers. To identify colonizing fungi, the
      eukaryotic rRNA operon's second internal transcribed spacer (ITS2) was sequenced
      from the stool, saliva, and food of healthy adults following consumption of
      different controlled diets. Unlike most bacterial 16S rRNA genes, the only fungal
      ITS2 operational taxonomic units (OTUs) detected in stool DNA across multiple
      diets were also present in saliva and/or food. Additional analyses, including
      culture-based approaches and sequencing of the 18S rRNA gene, ITS2 cDNA, and DNA
      extracted using alternative methods, failed to detect additional fungi. Two
      abundant fungi, Saccharomyces cerevisiae and Candida albicans, were examined
      further in healthy volunteers. Saccharomyces became undetectable in stool when a
      S. cerevisiae-free diet was consumed, and the levels of C. albicans in stool were
      dramatically reduced by more frequent cleaning of teeth. Extremely low fungal
      abundance, the inability of fungi to grow under conditions mimicking the distal
      gut, and evidence from analysis of other public datasets further support the
      hypothesis that fungi do not routinely colonize the GI tracts of healthy adults.
      IMPORTANCE We sought to identify the fungi that colonize healthy GI tracts and
      that have a sustained influence on the diverse functions of the gut microbiome.
      Instead, we found that all fungi in the stool of healthy volunteers could be
      explained by their presence in oral and dietary sources and that our results,
      together with those from other analyses, support the model that there is little
      or no gastrointestinal colonization by fungi. This may be due to Westernization,
      primate evolution, fungal ecology, and/or the strong defenses of a healthy immune
      system. Importantly, fungal colonization of the GI tract may often be indicative
      of disease. As fungi can cause serious infections in immunocompromised
      individuals and are found at increased abundance in multiple disorders of the GI
      tract, understanding normal fungal colonization is essential for proper treatment
      and prevention of fungal pathogenesis.

PMID- 29600284
TI  - Assembly, Biochemical Characterization, Immunogenicity, Adjuvanticity, and
      Efficacy of Shigella Artificial Invaplex.
AB  - The native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange
      purified product derived from the water extract of virulent Shigella species. The
      key component of InvaplexNAT is a high-molecular-mass complex (HMMC) consisting
      of the Shigella lipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC.
      To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR)
      was developed using recombinant IpaB and IpaC proteins and purified Shigella LPS
      to assemble an HMMC consisting of all three components. Characterization of
      InvaplexAR by various methods demonstrated similar characteristics as the
      previously reported HMMC in InvaplexNAT. The well-defined InvaplexAR vaccine
      consistently contained greater quantities of IpaB, IpaC, and LPS than
      InvaplexNAT. InvaplexAR and InvaplexNAT immunogenicities were compared in mouse
      and guinea pig dose escalation studies. In both models, immunization induced
      antibody responses specific for InvaplexNAT and LPS while InvaplexAR induced
      markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the
      murine model, homologous protection was achieved with 10-fold less InvaplexAR
      than InvaplexNAT and mice receiving InvaplexAR lost significantly less weight
      than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with
      InvaplexAR were protected from challenge with both homologous and heterologous
      Shigella serotypes. Guinea pigs receiving approximately 5-fold less InvaplexAR
      compared to cohorts immunized with InvaplexNAT were protected from ocular
      challenge. Furthermore, adjuvanticity previously attributed to InvaplexNAT was
      retained with InvaplexAR. The second-generation Shigella Invaplex vaccine,
      InvaplexAR, offers significant advantages over InvaplexNAT in reproducibility,
      flexible yet defined composition, immunogenicity, and protective efficacy.
      IMPORTANCEShigella species are bacteria that cause severe diarrheal disease
      worldwide, primarily in young children. Treatment of shigellosis includes oral
      fluids and antibiotics, but the high burden of disease, increasing prevalence of
      antibiotic resistance, and long-term health consequences clearly warrant the
      development of an effective vaccine. One Shigella vaccine under development is
      termed the invasin complex or Invaplex and is designed to drive an immune
      response to specific antigens of the bacteria in an effort to protect an
      individual from infection. The work presented here describes the production and
      evaluation of a new generation of Invaplex. The improved vaccine stimulates the
      production of antibodies in immunized mice and guinea pigs and protects these
      animals from Shigella infection. The next step in the product's development will
      be to test the safety and immune response induced in humans immunized with
      Invaplex.

PMID- 29600283
TI  - Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte
      and/or NK Cell Activity.
AB  - Zika virus (ZIKV) has reemerged in the population and caused unprecedented global
      outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied
      systematically first in human peripheral blood CD14+ monocytes and monocyte
      derived macrophages with high-density RNA sequencing. Analyses of the ZIKV genome
      revealed that the virus underwent genetic diversification, and differential mRNA
      abundance was found in host cells during infection. Notably, there was a
      significant change in the cellular response, with cross talk between monocytes
      and natural killer (NK) cells as one of the highly identified pathways.
      Immunophenotyping of peripheral blood from ZIKV-infected patients further
      confirmed the activation of NK cells during acute infection. ZIKV infection in
      peripheral blood cells isolated from healthy donors led to the induction of gamma
      interferon (IFN-gamma) and CD107a-two key markers of NK cell function. Depletion
      of CD14+ monocytes from peripheral blood resulted in a reduction of these markers
      and reduced priming of NK cells during infection. This was complemented by the
      immunoproteomic changes observed. Mechanistically, ZIKV infection preferentially
      counterbalances monocyte and/or NK cell activity, with implications for targeted
      cytokine immunotherapies. IMPORTANCE ZIKV reemerged in recent years, causing
      outbreaks in many parts of the world. Alarmingly, ZIKV infection has been
      associated with neurological complications such as Guillain-Barre syndrome (GBS)
      in adults and congenital fetal growth-associated anomalies in newborns. Host
      peripheral immune cells are one of the first to interact with the virus upon
      successful transmission from an infected female Aedes mosquito. However, little
      is known about the role of these immune cells during infection. In this work, the
      immune responses of monocytes, known target cells of ZIKV infection, were
      investigated by high-density transcriptomics. The analysis saw a robust immune
      response being elicited. Importantly, it also divulged that monocytes prime NK
      cell activities during virus infection. Removal of monocytes during the infection
      changed the immune milieu, which in turn reduced NK cell stimulation. This study
      provides valuable insights into the pathobiology of the virus and allows for the
      possibility of designing novel targeted therapeutics.

PMID- 29600285
TI  - Developing a Bacteroides System for Function-Based Screening of DNA from the
      Human Gut Microbiome.
AB  - Functional metagenomics is a powerful method that allows the isolation of genes
      whose role may not have been predicted from DNA sequence. In this approach,
      first, environmental DNA is cloned to generate metagenomic libraries that are
      maintained in Escherichia coli, and second, the cloned DNA is screened for
      activities of interest. Typically, functional screens are carried out using E.
      coli as a surrogate host, although there likely exist barriers to gene
      expression, such as lack of recognition of native promoters. Here, we describe
      efforts to develop Bacteroides thetaiotaomicron as a surrogate host for screening
      metagenomic DNA from the human gut. We construct a B. thetaiotaomicron-compatible
      fosmid cloning vector, generate a fosmid clone library using DNA from the human
      gut, and show successful functional complementation of a B. thetaiotaomicron
      glycan utilization mutant. Though we were unable to retrieve the physical fosmid
      after complementation, we used genome sequencing to identify the complementing
      genes derived from the human gut microbiome. Our results demonstrate that the use
      of B. thetaiotaomicron to express metagenomic DNA is promising, but they also
      exemplify the challenges that can be encountered in the development of new
      surrogate hosts for functional screening. IMPORTANCE Human gut microbiome
      research has been supported by advances in DNA sequencing that make it possible
      to obtain gigabases of sequence data from metagenomes but is limited by a lack of
      knowledge of gene function that leads to incomplete annotation of these data
      sets. There is a need for the development of methods that can provide
      experimental data regarding microbial gene function. Functional metagenomics is
      one such method, but functional screens are often carried out using hosts that
      may not be able to express the bulk of the environmental DNA being screened. We
      expand the range of current screening hosts and demonstrate that human gut
      derived metagenomic libraries can be introduced into the gut microbe Bacteroides
      thetaiotaomicron to identify genes based on activity screening. Our results
      support the continuing development of genetically tractable systems to obtain
      information about gene function.

PMID- 29600286
TI  - From Network Analysis to Functional Metabolic Modeling of the Human Gut
      Microbiota.
AB  - An important hallmark of the human gut microbiota is its species diversity and
      complexity. Various diseases have been associated with a decreased diversity
      leading to reduced metabolic functionalities. Common approaches to investigate
      the human microbiota include high-throughput sequencing with subsequent
      correlative analyses. However, to understand the ecology of the human gut
      microbiota and consequently design novel treatments for diseases, it is important
      to represent the different interactions between microbes with their associated
      metabolites. Computational systems biology approaches can give further
      mechanistic insights by constructing data- or knowledge-driven networks that
      represent microbe interactions. In this minireview, we will discuss current
      approaches in systems biology to analyze the human gut microbiota, with a
      particular focus on constraint-based modeling. We will discuss various community
      modeling techniques with their advantages and differences, as well as their
      application to predict the metabolic mechanisms of intestinal microbial
      communities. Finally, we will discuss future perspectives and current challenges
      of simulating realistic and comprehensive models of the human gut microbiota.

PMID- 29600287
TI  - luxR Homolog-Linked Biosynthetic Gene Clusters in Proteobacteria.
AB  - Microbes are a major source of antibiotics, pharmaceuticals, and other bioactive
      compounds. The production of many specialized microbial metabolites is encoded in
      biosynthetic gene clusters (BGCs). A challenge associated with natural product
      discovery is that many BGCs are not expressed under laboratory growth conditions.
      Here we report a genome-mining approach to discover BGCs with luxR-type quorum
      sensing (QS) genes, which code for regulatory proteins that control gene
      expression. Our results show that BGCs linked to genes coding for LuxR-like
      proteins are widespread in Proteobacteria. In addition, we show that associations
      between luxR homolog genes and BGCs have evolved independently many times, with
      functionally diverse gene clusters. Overall, these clusters may provide a source
      of new natural products for which there is some understanding about how to elicit
      production. IMPORTANCE Bacteria biosynthesize specialized metabolites with a
      variety of ecological functions, including defense against other microbes. Genes
      that code for specialized metabolite biosynthetic enzymes are frequently
      clustered together. These BGCs are often regulated by a transcription factor
      encoded within the cluster itself. These pathway-specific regulators respond to a
      signal or indirectly through other means of environmental sensing. Many
      specialized metabolites are not produced under laboratory growth conditions, and
      one reason for this issue is that laboratory growth media lack environmental cues
      necessary for BGC expression. Here, we report a bioinformatics study that reveals
      that BGCs are frequently linked to genes coding for LuxR family QS-responsive
      transcription factors in the phylum Proteobacteria. The products of these luxR
      homolog-associated gene clusters may serve as a practical source of bioactive
      metabolites.

PMID- 29600288
TI  - Diffusion Tensor Cardiac Magnetic Resonance Reveals Exosomes From Cardiosphere
      Derived Cells Preserve Myocardial Fiber Architecture After Myocardial Infarction.
AB  - The object of the study was to reveal the fiber microstructural response with
      diffusion tensor cardiac magnetic resonance after intramyocardial exosomes
      secreted by cardiosphere-derived cells (CDCEXO) in chronic porcine myocardial
      infarction. Porcine with myocardial infarction underwent intramyocardial delivery
      of human CDCEXO and placebo in a randomized placebo-controlled study. Four weeks
      after injection, viability improved in the CDCEXO group, whereas myocardial fiber
      architecture and cardiac function were preserved. In the placebo group, fiber
      architecture and cardiac function declined. Myocardial regeneration by CDCEXO is
      not tumor-like; instead, details of tissue architecture are faithfully preserved,
      which may foster physiological excitation and contraction.

PMID- 29600289
TI  - Advancing research in regeneration and repair of the motor circuitry: non-human
      primate models and imaging scales as the missing links for successfully
      translating injectable therapeutics to the clinic.
AB  - Regeneration and repair is the ultimate goal of therapeutics in trauma of the
      central nervous system (CNS). Stroke and spinal cord injury (SCI) are two highly
      prevalent CNS disorders that remain incurable, despite numerous research studies
      and the clinical need for effective treatments. Neural engineering is a diverse
      biomedical field, that addresses these diseases using new approaches. Research in
      the field involves principally rodent models and biologically active,
      biodegradable hydrogels. Promising results have been reported in preclinical
      studies of CNS repair, demonstrating the great potential for the development of
      new treatments for the brain, spinal cord and peripheral nerve injury. Several
      obstacles stand in the way of clinical translation of neuroregeneration research.
      There seems to be a key gap in the translation of research from rodent models to
      human applications, namely non-human primate models, which constitute a critical
      bridging step. Applying injectable therapeutics and multimodal neuroimaging in
      stroke lesions using experimental rhesus monkey models is an avenue that a few
      research groups have begun to embark on. Understanding and assessing the changes
      that the injured brain or spinal cord undergoes after an intervention with
      biodegradable hydrogels in non-human primates seem to represent critical
      preclinical research steps. Existing innovative models in non-human primates
      allow us to evaluate the potential of neural engineering and injectable
      hydrogels. The results of these preliminary studies will pave the way for
      translating this research into much needed clinical therapeutic approaches.
      Cutting edge imaging technology using Connectome scanners represents a tremendous
      advancement, enabling the in vivo, detailed, high-resolution evaluation of these
      therapeutic interventions in experimental animals. Most importantly, they also
      allow quantifiable and clinically meaningful correlations with humans, increasing
      the translatability of these innovations to the bedside.

PMID- 29600290
TI  - Reorientation of the Methyl Group in MAs(III) is the Rate-Limiting Step in the
      ArsM As(III) S-Adenosylmethionine Methyltransferase Reaction.
AB  - The most common biotransformation of trivalent inorganic arsenic (As(III)) is
      methylation to mono-, di-, and trimethylated species. Methylation is catalyzed by
      As(III) S-adenosylmethionine (SAM) methyltransferase (termed ArsM in microbes and
      AS3MT in animals). Methylarsenite (MAs(III)) is both the product of the first
      methylation step and the substrate of the second methylation step. When the rate
      of the overall methylation reaction was determined with As(III) as the substrate,
      the first methylation step was rapid, whereas the second methylation step was
      slow. In contrast, when MAs(III) was used as the substrate, the rate of
      methylation was as fast as the first methylation step when As(III) was used as
      the substrate. These results indicate that there is a slow conformational change
      between the first and second methylation steps. The structure of CmArsM from the
      thermophilic alga Cyanidioschyzon merolae sp. 5508 was determined with bound
      MAs(III) at 2.27 A resolution. The methyl group is facing the solvent, as would
      be expected when MAs(III) is bound as the substrate rather than facing the SAM
      binding site, as would be expected for MAs(III) as a product. We propose that the
      rate-limiting step in arsenic methylation is slow reorientation of the methyl
      group from the SAM-binding site to the solvent, which is linked to the
      conformation of the side chain of a conserved residue Tyr70.

PMID- 29600291
TI  - Multi-state models and missing covariate data: Expectation-Maximization algorithm
      for likelihood estimation.
AB  - Multi-state models have been widely used to analyze longitudinal event history
      data obtained in medical and epidemiological studies. The tools and methods
      developed recently in this area require completely observed data. However,
      missing data within variables of interest is very common in practice, and it has
      been an issue in applications. We propose a type of EM algorithm, which handles
      missingness within multiple binary covariates efficiently, for multi-state model
      applications. Simulation studies show that the EM algorithm performs well for
      both missing completely at random (MCAR) and missing at random (MAR) covariate
      data. We apply the method to a longitudinal aging and cognition study dataset,
      the Klamath Exceptional Aging Project (KEAP), whose data were collected at Oregon
      Health & Science University and integrated into the Statistical Models of Aging
      and Risk of Transition (SMART) database at the University of Kentucky.

PMID- 29600292
TI  - Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis
      by Nivolumab: A Prospective Study.
AB  - Context: Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD
      1) antibodies, have become promising treatments for a variety of advanced
      malignancies. However, these medicines can cause immune-related adverse events
      (irAEs), including endocrinopathies. Objective: This study examined the incidence
      of endocrine irAEs induced by nivolumab. Patients and Main Outcome Measured:
      Sixty-six patients treated with nivolumab at Nagoya University Hospital were
      prospectively evaluated for pituitary hormones, thyroid function, antithyroid
      antibodies (Abs), and glucose levels every 6 weeks after the initiation of
      nivolumab for 24 weeks. Results: Four out of 66 patients developed destructive
      thyroiditis, and three patients developed hypothyroidism requiring levothyroxine
      replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or
      anti-thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the
      group that developed destructive thyroiditis (3/4) compared with the group that
      did not develop thyroiditis (3/62; P = 0.002). There were no significant
      differences in other clinical variables between the groups. There were no
      endocrine irAEs other than destructive thyroiditis during the 24 weeks. The
      prevalence of TgAbs and/or TPOAbs at baseline was not associated with the
      development of other irAEs, including pneumonitis, colitis, or skin reactions.
      Conclusions: Our real-world data showed that destructive thyroiditis was an
      endocrine irAE that was frequently induced by nivolumab and was significantly
      associated with positive TgAbs and/or TPOAbs before treatment. Our findings
      indicate that evaluating these Abs before treatment may help identify patients
      with a high risk of thyroidal irAEs and may have important clinical benefit.

PMID- 29600293
TI  - USP8 Mutations in Pituitary Cushing Adenomas-Targeted Analysis by Next-Generation
      Sequencing.
AB  - Gain-of-function somatic mutations in the ubiquitin specific protease 8 (USP8)
      gene have recently been reported as a cause of pituitary adenomas in Cushing
      disease. Molecular diagnostic testing of tumor tissue may aid in the diagnosis of
      specimens obtained through therapeutic transsphenoidal surgery; however, for
      small tumors, availability of fresh tissue is limited, and contamination with
      normal tissue is frequent. We performed molecular testing of DNA isolated from
      single formalin-fixed and paraffin-embedded (FFPE) tissue sections of 42
      pituitary adenomas from patients with Cushing disease (27 female patients and 15
      male patients; mean age at surgery, 42.5 years; mean tumor size, 12.2 mm). By
      Sanger sequencing, we identified previously reported USP8 missense mutations in
      six tumors. Targeted next-generation sequencing (NGS) revealed known or
      previously undescribed missense mutations in three additional tumors (two with
      two different mutations each), with mutant allele frequencies as low as 3%. Of
      the nine tumors with USP8 mutations (mutation frequency, 21.4%), seven were from
      female patients (mutation frequency, 25.9%), and two were from male patients
      (mutation frequency, 13.3%). Mutant tumors were on average 11.4 mm in size, and
      patients with mutations were on average 43.9 years of age. The overall USP8
      mutation frequency in our cohort was lower than in previously described cohorts,
      and we did not observe USP8 deletions that were frequent in other cohorts. We
      demonstrate that testing for USP8 variants can be performed from small amounts of
      FFPE tissue. NGS showed higher sensitivity for USP8 mutation detection than did
      Sanger sequencing. Assessment for USP8 mutations may complement histopathological
      diagnosis.

PMID- 29600294
TI  - Characteristics of Glucose Metabolism in Underweight Japanese Women.
AB  - Context: Japanese women have substantially lower body mass index (BMI) than women
      in other developed countries. The BMI of Japanese women has steadily decreased
      over time. However, glucose metabolism in underweight Japanese women has not been
      fully characterized. Objective: The aim of this study was to investigate glucose
      metabolism and the physical characteristics of underweight Japanese women. Design
      and Participants: We recruited 31 young (20 to 29 years of age) and 30
      postmenopausal (50 to 65 years of age) underweight women. We also recruited young
      normal-weight women (n = 13) and postmenopausal normal-weight women (n = 10) to
      serve as references. We administered an oral glucose tolerance test (OGTT) and
      evaluated intramyocellular lipid (IMCL) levels and body composition using 1H
      magnetic resonance spectroscopy and dual-energy X-ray absorptiometry,
      respectively. Results: Young underweight women had similar glucose tolerance as
      young normal-weight women. However, postmenopausal underweight women had a higher
      area under the curve (AUC) for glucose during OGTT than postmenopausal normal
      weight women. In postmenopausal underweight women, 2-hour glucose levels during
      OGTT were negatively correlated with lean body mass (r = -0.55, P < 0.01) and
      insulinogenic index (r = -0.42, P = 0.02) and were positively correlated with
      IMCL levels (r = 0.40, P = 0.03). Compared with young underweight women,
      postmenopausal underweight women had a higher AUC for glucose during OGTT and a
      lower insulinogenic index and AUC for insulin during OGTT. Conclusions:
      Postmenopausal underweight women had more impaired glucose tolerance than young
      underweight women. In postmenopausal underweight women, the degree of glucose
      tolerance impairment was associated with decreased lean body mass, increased IMCL
      accumulation, and impaired insulin secretion.

PMID- 29600295
TI  - A 78-Year-Old Man With Historical Goiter.
AB  - The purpose of this paper is to provide description of the natural evolution of
      an initially operable goitre into unmesurable form in a context of deeply unknown
      psychiatric disorders initially unknown.

PMID- 29600296
TI  - Assessing the Effects of Software Platforms on Volumetric Segmentation of
      Glioblastoma.
AB  - Background: Radiological assessments of biologically relevant regions in
      glioblastoma have been associated with genotypic characteristics, implying a
      potential role in personalized medicine. Here, we assess the reproducibility and
      association with survival of two volumetric segmentation platforms and explore
      how methodology could impact subsequent interpretation and analysis. Methods:
      Post-contrast T1- and T2-weighted FLAIR MR images of 67 TCGA patients were
      segmented into five distinct compartments (necrosis, contrast-enhancement, FLAIR,
      post contrast abnormal, and total abnormal tumor volumes) by two quantitative
      image segmentation platforms - 3D Slicer and a method based on Velocity AI and
      FSL. We investigated the internal consistency of each platform by correlation
      statistics, association with survival, and concordance with consensus
      neuroradiologist ratings using ordinal logistic regression. Results: We found
      high correlations between the two platforms for FLAIR, post contrast abnormal,
      and total abnormal tumor volumes (spearman's r(67) = 0.952, 0.959, and 0.969
      respectively). Only modest agreement was observed for necrosis and contrast
      enhancement volumes (r(67) = 0.693 and 0.773 respectively), likely arising from
      differences in manual and automated segmentation methods of these regions by 3D
      Slicer and Velocity AI/FSL, respectively. Survival analysis based on AUC revealed
      significant predictive power of both platforms for the following volumes:
      contrast-enhancement, post contrast abnormal, and total abnormal tumor volumes.
      Finally, ordinal logistic regression demonstrated correspondence to manual
      ratings for several features. Conclusion: Tumor volume measurements from both
      volumetric platforms produced highly concordant and reproducible estimates across
      platforms for general features. As automated or semi-automated volumetric
      measurements replace manual linear or area measurements, it will become
      increasingly important to keep in mind that measurement differences between
      segmentation platforms for more detailed features could influence downstream
      survival or radio genomic analyses.

PMID- 29600302
TI  - Prevalence of Orofacial Changes in Wind Instrumentalists: A Cross-Sectional Pilot
      Study in Brazil.
AB  - OBJECTIVE: The aim of the present study was to identify the prevalence of
      orofacial changes and factors associated with the frequent playing of wind
      instruments by musicians in Diamantina, Minas Gerais, Brazil. METHODS: A cross
      sectional study was conducted with 40 professional musicians who played wind
      instruments. The musicians filled out questionnaires about their habits and
      musical career. The Research Diagnostic Criteria were applied to investigate
      temporomandibular disorders. Other oral parameters examined included periodontal
      status, plaque index, and decayed, missing, and filled teeth (DMF) index. A
      significance level of p<0.05 was adopted for statistical analysis. RESULTS: The
      population included 22 (55%) men and 18 (45%) women, with a mean age of 25.88
      yrs. The most common instruments played were the saxophone (n=12, 30%), clarinet
      (n=9, 22.5%), and flute (n=6, 15%). The most frequent pain complaint after
      playing was numbness in the upper lip or no sensation (25% of musicians), and the
      most frequent dental change observed was inclination of the upper teeth (15% of
      musicians). There was no significant association between dental changes, pain,
      and classification of instrument type. CONCLUSION: The main oral change that
      affected musicians who played wind instruments was the inclination of anterior
      teeth.

PMID- 29600303
TI  - Impact of Changes in Playing Time on Playing-Related Musculoskeletal Pain in
      String Music Students.
AB  - BACKGROUND: During their training, musicians must develop good work habits that
      they will carry on throughout their professional career in order to avoid
      potential chronic health problems, such as musculoskeletal pain. The effect of
      sudden changes in instrument playing-time on the development of playing-related
      musculoskeletal pain (PRMP) has not been thoroughly investigated in music
      students playing bowed string instruments (BSI), even though they are regularly
      exposed to such changes to perfect their playing skills. OBJECTIVE: To explore
      the association between sudden changes in instrument playing-time and changes in
      PRMP in BSI players. METHODS: A prospective cohort study was completed with BSI
      students attending a summer music camp offering high-level training. Participants
      completed a self-administered 23-item questionnaire designed for the study upon
      arrival at camp (T1) and then 7 days later (T2). RESULTS: Ninety-three BSI
      students (16+/-4 yrs old) completed the questionnaires, for a 23% response rate.
      Their playing-time increased by 23+/-14 hrs between T1 and T2. Complaints in pain
      frequency (e.g., from never to most of the time) and intensity (19+/-24 mm on
      VAS) significantly increased between T1 and T2 and were correlated with an
      increase in playing-time. CONCLUSION: A sudden increase in playing-time, such as
      that experienced by elite BSI students attending an intensive music camp, was
      related to an increase in PRMP. However, in this study, changes in pain
      characteristics were only partly explained by the change in playing-time.

PMID- 29600304
TI  - Health-Related Quality of Life in University Dance Students.
AB  - Injuries are common among dancers and may negatively affect health-related
      quality of life (HRQL). The modified Disablement in the Physically Active Scale
      (mDPA) is a generic patient-reported outcome instrument that could be used when
      providing care to patients participating in performing arts. The objective of
      this pilot study was to examine the internal consistency of the mDPA and assess
      overall HRQL using the mDPA in university dance students. Thirty-one female
      university dance students completed the mDPA during one data collection session.
      Higher scores on the Physical Summary Component (mDPA-PSC), the Mental Summary
      Component (mDPAMSC), and mDPA-Total indicated increased disablement. The internal
      consistency was determined using Cronbachs alpha. The mDPA-Total, mDPA-PSC, and
      mDPAMSC scores were examined descriptively using mean and standard deviations.
      Individual item responses were also examined. The proportion of university dance
      students with clinically relevant levels of disablement on the mDPA-Total was
      examined using a previously established minimally clinically important difference
      value. The internal consistency for the mDPA-MSC (a=0.91) and mDPATotal (a=0.90)
      was excellent and good for the mDPA-PSC (a=0.88). A large proportion (71%) of
      university dance students demonstrated clinically relevant levels of disablement
      despite fully participating in dance-related activities. Pain, impaired motion,
      and stress were the greatest contributors to increased disablement in these
      individuals. The mDPA scores observed in this pilot study indicate that many
      dance students experience levels of disablement and decreased HRQL which may
      warrant physical and mental intervention. Clinicians providing healthcare
      services to performing artists should consider using the mDPA to provide patient
      centered care.

PMID- 29600305
TI  - Comparison of Lower Extremity Muscle Flexibility in Amateur and Trained
      Bharatanatyam Dancers and Nondancers.
AB  - OBJECTIVE: This study compared lower limb muscle flexibility between amateur and
      trained female Bharatanatyam dancers and nondancers. METHODS: Subjects consisted
      of 105 healthy female volunteers, with 70 female Bharatanatyam dancers (35
      trained, 35 amateurs) and 35 controls, with a mean (+/-SD) age of 16.2+/-1.04
      yrs, height 155.05+/-4.30 cm, and weight 54.54+/-2.77 kg. Participants were
      assessed for range of motion (ROM) in hip flexion, hip extension, hip abduction
      and adduction, hip external rotation, hip internal rotation, knee flexion, knee
      extension, ankle dorsiflexion (DF), and ankle plantar flexion (PF) by using a
      standardized goniometer. To assess for significant difference between groups, one
      way ANOVA was applied, and multiple comparisons were made using Bonferroni
      correction. RESULTS: Trained dancers had a significantly greater hip flexion,
      extension, abduction, and external rotation ROM than amateurs and nondancers
      (p<0.05). Also, internal rotation and adduction were markedly less in trained
      dancers (p<0.05). Knee flexion, extension, and ankle DF were higher and ankle PF
      ROM was lesser in trained dancers. However, not much variation was found in ankle
      DF and PF between amateur dancers and nondancers (p>0.05). CONCLUSION: Results
      showed that there are significant differences in lower limb muscle flexibility
      between trained and amateur Bharatanatyam dancers and nondancers. These
      differences may be due to individual dance postures such as araimandi and
      muzhumandi.

PMID- 29600306
TI  - Epidemiology, Treatment Efficacy, and Anxiety Aspects of Music Students Affected
      by Playing-Related Pain: A Retrospective Evaluation with Follow-up.
AB  - OBJECTIVES: Playing-related pain (PRP) is a common problem among music students.
      We retrospectively assessed epidemiological factors that contributed to the
      manifestation of PRP and evaluated the efficacy of treatment methods used by
      affected music students. The long-term course of PRP symptoms was also examined,
      along with current (today) levels of trait anxieties. METHODS: Demographic and
      epidemiological data of 186 music students who visited the musicians' outpatient
      clinic over a 5-year period were retrieved. Of these students, 122 had been
      diagnosed with PRP and were invited to participate (response rate 61.5%) in a
      follow-up online survey to: a) estimate the long-term course of their PRP
      symptoms, b) assess the efficacy of treatment methods they used, and c) assess
      their current trait anxiety (general and performance-related) using two
      standardized psychodiagnostic questionnaires. RESULTS: Two-thirds of music
      students who sought medical care were affected by PRP, with most being affected
      during their first year of studies, and with 69% having acute rather than chronic
      pain. The sudden increase in practice time was the main triggering factor for PRP
      (but not for non-PRP-related problems). Concerning the course of PRP, almost all
      students recovered or improved significantly. Students reported that "active"
      treatment methods (e.g., physical activities) were more effective than "passive"
      methods (e.g., oral medications). Psychodiagnostic questionnaires indicated that
      about 40% of PRP-affected students currently had increased levels of trait
      anxieties (music and non-music related), possibly warranting further medical
      assistance. CONCLUSIONS: PRP in music students occurs mainly at the beginning of
      their studies and has a good prognosis, although recovery may be lengthy. It is
      necessary to provide students with early information about PRP and about the
      multidimensional treatment framework that allows for individualized care of PRP
      in affected music students.

PMID- 29600307
TI  - Effects of Aging on Musical Performance in Professional Orchestral Musicians.
AB  - BACKGROUND: The physical and psychological demands of playing a musical
      instrument are likely to be affected by age-related decline in function,
      including physical, cognitive, psychological, and organ-related changes. However,
      the complex neurophysiological demands of playing a musical instrument may delay
      many normal aging-related changes. AIM: This study compared professional
      classical musicians of different ages, using a range of physical and
      psychological measures, to discover how increasing age might affect work
      performance and to identify possible risk and protective factors for physical and
      psychological health as the musicians age. SUBJECTS: 377 professional orchestral
      musicians from eight Australian orchestras (70% response rate), ages 18 to 68 yrs
      (mean 42.1). Multiple standardized physical and psychological tools were used to
      evaluate the impact of age on a range of physical and mental health variables.
      RESULTS: Age was not statistically associated with frequency or severity of
      performance-related musculoskeletal disorders, ratings of perceived exertion,
      QuickDASH scores, use of beta-blockers, workplace satisfaction, and most
      psychological tests. Differences were observed on SPIN (social anxiety) scores,
      with lowest scores in the oldest age group (10.66 in 55+ yrs vs 17.83 in 18-30
      yrs, p=0.016). Older musicians had higher BMIs and fewer practice sessions per
      day than younger musicians and also were more likely to consume alcohol on 5+
      days/wk (44% vs 9%, p=0.003). CONCLUSION: Advancing age does not appear to exert
      undue negative impacts on physical and psychological health or performance
      capacity of professional orchestral musicians. However, dwindling numbers in the
      older age groups may suggest a "survivor" effect, whereby those who develop
      significant age-related decrements may cease professional performance at earlier
      ages. Longitudinal studies on the professional trajectories of professional
      orchestral musicians are needed to explore this question further.

PMID- 29600308
TI  - Extent of Playing-Related Musculoskeletal Problems in the Irish Traditional Music
      Community: A Survey.
AB  - BACKGROUND: The literature related to playing-related musculoskeletal disorders
      (PRMDs) primarily includes classical musicians and instrument-specific studies.
      Previous work by our team identified that PRMDs are an issue for Irish
      traditional fiddle players; however, the extent of the problem was not known.
      OBJECTIVE: To identify the type and extent of PRMDs in the Irish traditional
      music population, specifically fiddle players. METHODS: A questionnaire was
      developed and administered to faculty and students related to all Irish
      traditional music courses in all higher education institutions in Ireland.
      RESULTS: Seven institutions were included. The response rate was 77.5% (n=79 of
      102 possible respondents). A fifth of respondents never had a PRMD, 36.7% (n=29)
      currently had a PRMD, and 34.2% (n=27) had a previous experience of a PRMD. The
      main symptoms were pain (62%, n=49), stiffness (41.8%, n=33), and tingling
      (35.4%, n=28). There was a positive association between the development of PRMDs
      and increased hours of play (p=0.017). CONCLUSIONS: PRMDs are a problem for Irish
      traditional fiddle players, especially during times of intense playing such as
      festivals.

PMID- 29600309
TI  - Musculoskeletal Assessments Used in Quantitatively Based Studies About Posture
      and Movement in High String Players: A Systematic Review.
AB  - OBJECTIVE: The aim of the study was to identify and systematically categorize
      musculoskeletal assessments used in quantitatively based studies about posture
      and movement in musicians playing high string instruments (violin, viola) in
      order to inform further research and help to identify gaps in knowledge. METHODS:
      A systematic literature search was conducted in the databases Cochrane, CINAHL,
      and PubMed as well as the journal Medical Problems of Performing Artists.
      Additional studies were searched within the reference lists of relevant articles.
      Sixty-four studies conducted since 1999 until May 2017 were included according to
      predefined inclusion criteria. RESULTS: Various biomechanical measurement
      instruments were used in 24 of the selected studies in order to collect two- and
      three-dimensional kinematic data: optoelectronic systems with active and passive
      markers, electromagnetic systems, ultrasonic motion analysis systems, and image
      based analysis of posture. In 11 studies, kinetics were measured by
      optoelectronic systems, force sensors, and a posturographic device. Further
      studies used electromyography to evaluate muscle activity (19 studies) as well as
      instruments to measure range of motion (2 studies). Additionally, a broad range
      of clinical examination techniques (35 studies) and self-reports (36 studies)
      were used to assess the musculoskeletal system of high string players.
      CONCLUSION: The identified assessments could be used both in further research and
      in practical work in order to evaluate posture and movement in high string
      players. For future research, qualitatively based studies as well as
      psychometrically tested quantitatively based self-report assessments are
      required.

PMID- 29600310
TI  - Pain Across Artists' Lifespan.
AB  - Having a lifelong career as a professional performing artist carries both
      challenges and benefits across different body systems. Pushing one's body to the
      limits results in a higher risk of suffering from some kind of episode of
      overload, whether it be physical or psychological. Indeed, a sudden increase in
      playing load (overtraining) is linked with increased frequency and intensity of
      pain or performance-related musculoskeletal disorders in both dance and music
      student populations. In this issue, research highlights this across the lifespan
      and in different genres of performing arts, including Irish fiddlers.

PMID- 29600311
TI  - Comparison of the diagnostic values of vascular adhesion protein-1 and intestinal
      fatty acid-binding protein in the diagnosis of acute mesenteric ischemia.
AB  - OBJECTIVES: The aim of this study is to compare the diagnostic values of plasma
      levels of vascular adhesion protein-1 (VAP-1) and intestinal fatty acid-binding
      protein (I-FABP) for diagnosing acute mesenteric ischemia (AMI). METHODS: The
      study used a randomized, controlled experimental design. Forty-two female Sprague
      Dawley rats were divided into three control groups and three ischemia groups.
      Plasma VAP-1 and I-FABP levels were measured, and the extent of ischemic damage
      was determined using a histopathological damage score in terminal ileum tissue
      samples. RESULTS: In the early phase of AMI (i.e. at the 30-min time point), VAP
      1 levels did not differ between the control and ischemia groups (p > 0.05), but I
      FABP levels were significantly higher in the ischaemia groups (p = 0.017).
      Although both VAP-1 and I-FABP levels increased in the ischaemia groups, only VAP
      1 levels showed a significant increase compared to the control group at the 2-h
      time point (p = 0.011). Ischemic damages associated with AMI became the most
      prominent at the 6-h time point. During this phase, both VAP-1 and I-FABP levels
      were significantly higher in the ischemia groups than in the control groups (p =
      0.007 and p = 0.002, respectively). Both VAP-1 and I-FABP levels showed a
      significant correlation with ischemic changes, but a higher correlation was
      observed for VAP-1 levels (r = 0.771). CONCLUSIONS: Both I-FABP and VAP-1 levels
      were useful for diagnosing AMI, but VAP-1 levels correlated better with the
      extent of ischaemic damage.

PMID- 29600312
TI  - Development of eco-friendly process for the production of bioethanol from banana
      peel using inhouse developed cocktail of thermo-alkali-stable depolymerizing
      enzymes.
AB  - Conversion of agro-industrial wastes to energy is an innovative approach for
      waste valorization and management which also mitigates environmental pollution.
      In this view, present study investigated the feasibility of producing bioethanol
      from banana peels using cocktail of depolymerizing enzyme/s. We isolated
      Geobacillus stearothermophilus HPA19 from natural resource which produces
      cocktail of thermo-alkali-stable xylano-pectino-cellulolytic enzyme/s using wheat
      bran within 24 h. The optimal temperature and pH for xylanase, filter paper
      cellulase and pectinase were 80, 70 and 80  degrees C, and 9.0, 8.0 and 9.0,
      respectively. Cocktail enzymes showed stability at high temperature (80  degrees
      C) and pH (10.0). Ni2+ and Zn2+ promoted the relative activity of xylanase and
      FPase, whereas Na+, Ca2+ and K+ promoted pectinase activity. Cocktail was
      assessed in saccharification of banana peel. Reducing sugar obtained (37.06 mg ml
      1) after one variable at a time (OVAT) method is greatly influenced by enzyme
      dose. Further, response surface methodology was used to optimize saccharification
      leading to twofold increase in reducing sugar. Maximum ethanol production (21.1
      gl-1) was achieved through fermentation giving the efficiency of 76.5% within 30
      h. Hence utilization of waste biomass for production of value-added products
      through biotechnological intervention not only helps to combat environmental
      pollution but also contributes significantly to the economy.

PMID- 29600313
TI  - Comparison of 1p and 19q status of glioblastoma by whole exome sequencing, array
      comparative genomic hybridization, and fluorescence in situ hybridization.
AB  - According to the 2016 World Health Organization classification of tumors of the
      central nervous system, detecting 1p/19q co-deletion became essential in clinical
      neuropathology for gliomas with oligodendroglioma-like morphology. Here, we
      assessed genomic profiles of glioblastoma in 80 cases including 1p/19q status
      using fluorescent in situ hybridization (FISH), array-comparative genomic
      hybridization (aCGH), and/or whole exome sequencing (WES). Paraffin-embedded
      tumor tissues were subjected to FISH analysis, and the corresponding frozen
      tissues from the same tumors were evaluated for aCGH and/or WES for 1p/19q co
      deletion and other genetic parameters, which included IDH1-R132H, ATRX, TP53,
      CIC, and NOTCH1 mutations and MGMT methylation status. We also evaluated
      correlations between 1p/19q co-deletion status and molecular markers or clinical
      outcomes. The FISH analyses revealed 1p/19q co-deletion in two cases, isolated
      deletion of 1p in six cases, and 19q in two cases, whereas the aCGH and WES
      results showed isolated deletion of 19q in four cases and 19 monosomy in only one
      case. Eleven cases showed discordant 1p/19q results between aCGH/WES and FISH
      analysis, and in most of them, 1p and/or 19q deletion on FISH analysis
      corresponded to the partial deletions at 1p36 and/or 19q13 on aCGH/WES. Our
      cohort exhibited IDH1-R132H mutations (5.4%), MGMT promotor methylation (34.6%),
      and mutations in ATRX (9.5%), TP53 (33.3%), and NOTCH1 (3.8%) but not in CIC
      (0%). In addition, MGMT methylation and ATRX mutation were significantly
      associated with clinical prognosis. In glioblastomas, partial deletions of 1p36
      and/or 19q13 were uncommon, some of which appeared as 1p and/or 19q deletions on
      FISH analysis.

PMID- 29600314
TI  - Leaf area and photosynthesis of newly emerged trifoliolate leaves are regulated
      by mature leaves in soybean.
AB  - Leaf anatomy and the stomatal development of developing leaves of plants have
      been shown to be regulated by the same light environment as that of mature
      leaves, but no report has yet been written on whether such a long-distance signal
      from mature leaves regulates the total leaf area of newly emerged leaves. To
      explore this question, we created an investigation in which we collected data on
      the leaf area, leaf mass per area (LMA), leaf anatomy, cell size, cell number,
      gas exchange and soluble sugar content of leaves from three soybean varieties
      grown under full sunlight (NS), shaded mature leaves (MS) or whole plants grown
      in shade (WS). Our results show that MS or WS cause a marked decline both in leaf
      area and LMA in newly developing leaves. Leaf anatomy also showed characteristics
      of shade leaves with decreased leaf thickness, palisade tissue thickness, sponge
      tissue thickness, cell size and cell numbers. In addition, in the MS and WS
      treatments, newly developed leaves exhibited lower net photosynthetic rate (Pn),
      stomatal conductance (Gs) and transpiration rate (E), but higher carbon dioxide
      (CO 2 ) concentration in the intercellular space (Ci) than plants grown in full
      sunlight. Moreover, soluble sugar content was significantly decreased in newly
      developed leaves in MS and WS treatments. These results clearly indicate that (1)
      leaf area, leaf anatomical structure, and photosynthetic function of newly
      developing leaves are regulated by a systemic irradiance signal from mature
      leaves; (2) decreased cell size and cell number are the major cause of smaller
      and thinner leaves in shade; and (3) sugars could possibly act as candidate
      signal substances to regulate leaf area systemically.

PMID- 29600315
TI  - Integrated taxonomy of the Asplenium normale complex (Aspleniaceae) in China and
      adjacent areas.
AB  - The Asplenium normale D. Don complex comprises several taxa that are either
      diploid or tetraploid. The tetraploids are assumed to have originated from
      diploid ancestors by relatively recent autopolyploidization or
      allopolyploidization. Some of the diploids are readily recognized morphologically
      but most of the taxa have until now been placed into a single species. However,
      phylogenetic studies have challenged this treatment and emphasized the notion
      that the taxonomic treatment of this complex needs to be revised. An integrative
      taxonomic approach was employed to delimit species in the complex using
      cytological, morphological, and DNA sequence data. Initially, we employed a
      diploid first approach to establish a robust taxonomic framework. Special efforts
      were made to collect and identify the diploid progenitors of each polyploid
      lineage identified in the plastid DNA based phylogenetic hypothesis. A total of
      six distinct diploid species were identified. The distinctive nature of the six
      diploids is strongly supported by sequence differences in plastid DNA and nuclear
      loci, as well as by the results of morphometric analysis. Diagnostic
      morphological characters were identified to distinguish the six diploid species,
      resulting in their revised taxonomy, which includes two novel species, namely,
      Asplenium normaloides and A. guangdongense. Further studies to strengthen the
      taxonomic classification of all of the tetraploid taxa are warranted.

PMID- 29600316
TI  - Optimization of a Bioluminescence Resonance Energy Transfer-Based Assay for
      Screening of Trypanosoma cruzi Protein/Protein Interaction Inhibitors.
AB  - Chagas disease, a parasitic disease caused by Trypanosoma cruzi, is a major
      public health burden in poor rural populations of Central and South America and a
      serious emerging threat outside the endemic region, since the number of
      infections in non-endemic countries continues to rise. In order to develop more
      efficient anti-trypanosomal treatments to replace the outdated therapies, new
      molecular targets need to be explored and new drugs discovered. Trypanosoma cruzi
      has distinctive structural and functional characteristics with respect to the
      human host. These exclusive features could emerge as interesting drug targets. In
      this work, essential and differential protein-protein interactions for the
      parasite, including the ribosomal P proteins and proteins involved in mRNA
      processing, were evaluated in a bioluminescence resonance energy transfer-based
      assay as a starting point for drug screening. Suitable conditions to consider
      using this simple and robust methodology to screening compounds and natural
      extracts able to inhibit protein-protein interactions were set in living cells
      and lysates.

PMID- 29600317
TI  - Septal branches of the anterior ethmoidal artery: anatomical considerations and
      clinical implications in the management of refractory epistaxis.
AB  - PURPOSE: Epistaxis is a commonly presenting complaint. In severe cases,
      nosebleeds may occur despite antero-posterior nasal packing and often in the
      absence of identifiable sources of bleeding. In such cases, epistaxis may occur
      from septal branches of the anterior ethmoidal artery (sbAEA). The purposes of
      this study are to highlight the clinical role of the sbAEA in different fields of
      endoscopic endonasal surgery and to evaluate the efficacy and safety of their
      selective endoscopic endonasal ligation in the management of refractory
      epistaxis. METHODS: A retrospective review was performed of all patients
      presenting with epistaxis who underwent endoscopic endonasal coagulation of sbAEA
      in three Italian tertiary-care referral centers between October 2010 and October
      2017. RESULTS: A total of 30 patients met the inclusion criteria. Sixteen
      patients had never experienced nosebleeds before, while 14 patients recalled
      previous epistaxes. Seventeen patients were treated under local anesthetic, while
      13 required general anesthesia. No intra- or post-operative complications were
      observed and none of the patients received nasal packing after the procedure. In
      all cases the coagulation was effective in controlling the bleeding, with only
      two relapses in the series (2/30, 6.7%). CONCLUSIONS: The sbAEA are of great
      interest in endoscopic endonasal surgery, both as surgical landmarks and as
      feeding vessels for a variety of pedicled nasal flaps. What is more, they can be
      crucial for the management of refractory epistaxis. Their selective endoscopic
      coagulation represents an effective and safe procedure in cases of difficult-to
      control epistaxis from the upper nasal fossa, with several advantages over nasal
      packing.

PMID- 29600318
TI  - Do turbinate reduction procedures restore epithelial integrity in patients with
      turbinate hypertrophy secondary to allergic rhinitis? A histopathological study.
AB  - PURPOSE: Consensus has not been reached regarding the optimal reduction procedure
      for inferior turbinate hypertrophy in allergic rhinitis and whether such
      procedures result in improvement in mucosal architecture. METHODS: Twenty-nine
      patients aged 18-45 years (mean 26.8 years), with allergic rhinitis and inferior
      turbinate hypertrophy not responsive to medical therapy who underwent endoscopic
      submucosal diathermy (ESMD) (14 patients) or endoscopic submucosal resection
      (ESMR) (15 patients) with intraoperative and 3-6 months postoperative inferior
      turbinate biopsies, were included in the study. Epithelial and mucosal
      architecture was compared between the two groups. RESULTS: Both groups showed a
      significant decrease in epithelial denudation (p < 0.001), reversal of basement
      membrane thickening (p < 0.001) and increase in density of cilia (p < 0.001). The
      degree of improvement in histological characteristics between ESMD and ESMR
      groups was not significant. CONCLUSIONS: Surgical intervention for inferior
      turbinate hypertrophy by both ESMD and ESMR results in significant restoration of
      nasal mucosal epithelium in patients with allergic rhinitis as early as 3-month
      postoperatively. There was, however, no significant difference in the
      histological changes between those who underwent ESMD and ESMR. CLINICAL TRIALS
      OF INDIA, REGISTRY NUMBER: CTRI/2015/01/005373.

PMID- 29600319
TI  - Patients with unilateral squamous cell carcinoma of the tongue and ipsilateral
      lymph node metastasis do not profit from bilateral neck dissection.
AB  - OBJECTIVES: The purpose of this study was to evaluate the necessity of elective
      bilateral neck dissection for treating strict unilateral squamous cell carcinoma
      (SCC) of the tongue. METHODS: A cohort of 169 patients with unilateral non
      midline crossing SCCs of the tongue treated by local resection and neck
      dissection was investigated. Study endpoints were nodal relapse and overall
      survival. The mean follow-up was 7.4 years. RESULTS: A total of 146 (88.1%)
      patients were treated by neck dissection. Lymph node metastases were diagnosed in
      50 (34.2%) patients. Only two (1.1%) had contralateral lymph node metastases.
      Risk factors for developing a primary lymph node metastasis were size of tumor
      (T2/T3, p = 0.03; OR = 2.2), lymphangiosis (p = 0.003; OR = 4.7), and higher
      grade differentiation (p = 0.051; OR = 2.43). Metachronous lymph node metastases
      were detected in 23 (13.6%) patients (19 ipsilateral, one contralateral and three
      bilateral). The main risk factor for developing a metachronous lymph node
      metastasis was the presence of a primary lymph node metastasis (p = 0.004; HR =
      4.65). Patients with initial neck dissection came up with lower 5-year recurrence
      rates (13.6%) compared to patients without neck dissection (27.3%; p = 0.014).
      Bilateral neck dissection showed no advantage regarding nodal relapse free and
      overall survival (p = 0.606) compared to unilateral neck dissection irrespective
      of initial N or T stage. CONCLUSION: Patients with unilateral SCC of the tongue
      benefit from an ipsilateral neck dissection regarding nodal relapse. The value of
      elective bilateral neck dissection as standard treatment seems questionable even
      if positive lymph nodes were diagnosed ipsilateral at primary therapy.

PMID- 29600320
TI  - Early results of total arch replacement under partial sternotomy.
AB  - OBJECTIVE: Partial sternotomy with limited skin incision has been utilized for
      cardiac surgery. We, therefore, started to apply the partial sternotomy for total
      arch replacement since 2013 in selected cases. The aim of this study reported the
      results of our early experiences. METHODS: Between July 2013 and December 2015,
      we retrospectively reviewed 15 cases (median age 72, range 67-84, 15 male) who
      underwent total arch replacement thorough partial sternotomy. All procedures were
      performed under hypothermic circulatory arrest with selective cerebral perfusion.
      RESULTS: Median skin incision was 9 cm (range 7-15 cm, 5.3% of height) and
      partial sternotomy consisted of 14 upper and 1 lower partial sternotomy (L shape
      8 and T shape 7 cases). Median operation time, cardiopulmonary bypass time,
      ischemic heart time, selective cerebral perfusion time and hypothermic
      circulatory arrest time were 485 [360-770], 223 [1174-270], 146 [100-163], 154
      [116-189], and 69 [45-90] minutes, respectively. Median duration of mechanical
      ventilator dependent time was 12 h [5-38]. Median length of ICU stay and hospital
      stay were 3 [1-7], and 18 [13-76] days, respectively. Thirty days and in-hospital
      mortality were 0% without any neurological complications. There are two aorta
      related reoperation due to graft inducing hemolytic anemia and no aorta-related
      death during follow-up (median 954, range 702-1462 days). CONCLUSION: The early
      results of total arch replacement through partial sternotomy were satisfactory.
      The partial sternotomy could be a good option for total arch replacement in
      selected patients.

PMID- 29600321
TI  - Can ebselen prevent cisplatin-induced ovarian damage?
AB  - PURPOSE: The occurrence of ovarian damage is a major shortcoming in treating
      tumors with cisplatin (CP). The present study investigates the beneficial effects
      of ebselen-a seleno-organic compound with antioxidant and antiinflammatory
      properties-vis-a-vis CP-induced ovarian damage. METHODS: Twenty-eight adult
      female rats were divided into four study groups. Group 1 received no treatment.
      The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2
      mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline
      (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in
      Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline
      intraperitoneally 60 min before each CP treatment. The rats in Group 4 were
      pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min
      before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric
      oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and
      catalase levels, as well as histopathological damage scores (HDSs) and serum
      antimullerian hormone (AMH) levels, were assessed. RESULTS: Cu/Zn-SOD and GSH
      levels were significantly higher, and MDA and NOx levels significantly lower, in
      Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved
      serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were
      significantly lower in Group 4 than in Groups 2 and 3. CONCLUSIONS: Our results
      from using an experimental rat model of CP chemotherapy suggest that ebselen use
      may ameliorate ovarian damage by preventing oxidative injury.

PMID- 29600322
TI  - Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for
      IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta
      analysis.
AB  - PURPOSE: To summarize available evidence from randomized-controlled trials which
      have evaluated triggering of final oocyte maturation with concomitant GnRH
      agonists and hCG in patients undergoing IVF, and to analyze whether dual
      triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy
      outcomes. METHODS: A comprehensive literature search was performed to identify
      randomized-controlled trials comparing IVF outcomes between women receiving
      combined administration of hCG with GnRH agonists and those receiving hCG alone
      for triggering of final oocyte maturation. RESULTS: Four studies including 527
      patients eligible for inclusion in meta-analysis were identified. No significant
      difference in the number of mature oocytes or fertilized oocytes retrieved was
      found between groups. Clinical pregnancy rate with dual triggering was
      significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95%
      CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing
      pregnancy rate between groups. CONCLUSION: Results of meta-analysis indicate
      comparable or significantly improved outcomes with the use of GnRH agonists plus
      hCG as compared with hCG alone for triggering of final oocyte maturation.

PMID- 29600323
TI  - Assessment of polyurethane spheres as surrogates for military ballistic head
      injury.
AB  - SYNBONE(r) spheres were impacted with 7.62 * 39 mm mild steel core ammunition at
      a mean impact velocity of 654 m/s, SD 7 m/s, to simulate engagement distances of
      around 50-100 m. The wounds and fracture patterns were assessed by two forensic
      pathologists familiar with military cranial injury. The overall fracture pattern
      was assessed as being too comminuted when compared with actual injury. This
      suggests the SYNBONE(r) spheres have less utility for simulating military injury
      than other purposes described in the literature.

PMID- 29600324
TI  - A toolkit for the management of infection or colonization by extended-spectrum
      beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome
      of a European project.
AB  - Among European countries, prevalence rates of extended-spectrum beta-lactamase
      producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering
      the Mediterranean. This is the case for Italy, with 26% of Escherichia coli
      displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E
      toolkit designed to assist clinicians in managing patients harboring ESBL-E was
      favorably implemented in Southern France. In a context of lack of specific
      Italian recommendations, its extension to an adjacent region of Italy was made
      possible through a cross-border EU cooperation program. Italian infectious
      disease (ID) specialists, microbiologists, and community-based general
      practitioners from three districts in Liguria were offered a toolkit consisting
      in a warning system and detailed procedures for the management of patients
      harboring ESBL-E, including seeking advice from an ID specialist, and were
      trained during 52 video conferences by an experienced French team. Indications
      and trends in antimicrobial prescription were studied following implementation of
      the toolkit. Between November 2013 and November 2014, 476 patients were
      identified as harboring ESBL-E and expert advice was sought for 364 of these; all
      patients and/or their caregivers were advised on appropriate hygiene measures and
      209/341 with documented management received antimicrobial treatment, while
      asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit
      was well received by the healthcare staff. A specific, simple tool consisting in
      a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial
      prescription to symptomatic patients while raising awareness among caregivers of
      the importance of seeking expert advice and implementing appropriate hygiene
      measures.

PMID- 29600325
TI  - Associations between biomarkers at discharge and co-morbidities and risk of
      readmission after community-acquired pneumonia: a retrospective cohort study.
AB  - To investigate whether hemoglobin, white blood cell count (WBC), urea, sodium,
      albumin, and C-reactive protein at discharge in patients hospitalized for
      community-acquired pneumonia (CAP) are associated with 30-day readmission. This
      study is a retrospective cohort study, which included all adult patients
      discharged after hospitalization for CAP from three Danish hospitals between
      January 2011 and July 2012. The outcome was all-cause, unplanned, 30-day
      readmission. Biomarker concentrations at discharge were transformed into binary
      variables by using either upper or lower quartiles as cut-off; the upper quartile
      was used for WBC, urea, and C-reactive protein, and the lower quartile was used
      for hemoglobin, sodium, and albumin. The study population consisted of 1149
      patients. One hundred eighty-four (16.0%) patients were readmitted. Independent
      risk factors of readmission were WBC >= 10.6 cells * 109/L (hazard ratio 1.50;
      95% CI, 1.07-2.11) and albumin <32 g/L (hazard ratio 1.78; 95% CI, 1.24-2.54) at
      discharge and the presence of >= 2 co-morbidities (hazard ratio 1.74; 95% CI,
      1.15-2.64). When WBC, albumin, and co-morbidities were combined into a risk
      stratification tool, there was a step-wise increase in risk of readmission for
      patients with 1, 2, or 3 risk factors with hazard ratios of 1.76 (95% CI, 1.25
      2.49), 2.59 (95% CI, 1.71-3.93), and 6.15 (95% CI 3.33-11.38), respectively. WBC
      >= 10.6 cells * 109/L and albumin < 32 g/L at discharge and the presence of >= 2
      co-morbidities were independently associated with increased risk of 30-day
      readmission.

PMID- 29600326
TI  - Right trisegmentectomy after portal vein embolization in a high-risk toddler with
      hepatoblastoma.
AB  - Portal vein embolization (PVE) is a pre-operative treatment modality in adults
      undergoing hepatectomy with concerns of post-operative liver failure from
      insufficient future liver remnant (FLR). PVE induces growth in the FLR. The
      success of this technique is well described in adults, but not in young children
      with hepatoblastoma.

PMID- 29600328
TI  - Cross-sectional association of dietary water intakes and sources, and adiposity:
      National Adult Nutrition Survey, the Republic of Ireland.
AB  - PURPOSE: Drinking (plain) water intake has been associated with weight loss and
      reducing energy intake in intervention trials. In free-living populations,
      replacing other beverages with drinking water is associated with reduced obesity
      risk. However, the association of total water intake and its sources, and body
      fat distribution remain unevaluated. Thus, the aim of this study was to
      investigate total water intake and its sources and the association with
      anthropometric measures. METHODS: Cross-sectional study of 1500 adults aged 18-90
      years (Irish National Adult Nutrition Survey, 2008-2010). Total water intake and
      its sources were estimated using food records. Associations of total water,
      drinking water, beverage moisture and food moisture intakes split by tertile, and
      BMI (kg/m2), waist circumference (cm), and bio-impedance derived body fat (%)
      were evaluated using covariate-adjusted linear regression analyses including
      adjustment for energy intake and energy expenditure. RESULTS: Higher consumption
      of total water was associated with lower waist circumference [beta-coefficient
      (95% CI), p trend, tertile 3 versus tertile 1: - 2.19 (- 4.06, - 0.32), 0.036],
      but not BMI [- 0.44 (- 1.16, 0.28), 0.336] or body fat [- 0.87 (- 1.91, 0.17),
      0.146]. Higher consumption of drinking water and food moisture were associated
      with lower BMI [- 0.65 (- 1.30, - 0.01), 0.027; - 0.64 (- 1.41, - 0.13), 0.014,
      respectively], body fat [- 1.51 (- 2.43, - 0.59), 0.001; - 1.00 (- 2.12, - 0.12),
      0.001], and waist circumference [- 2.83 (- 4.51, - 1.16), < 0.001; - 1.84 (-
      3.86, - 0.19), 0.082]. Beverage moisture was not associated with any of the
      anthropometric measurements. CONCLUSIONS: Consumption of drinking water and food
      moisture and not total water or beverage moisture were inversely associated with
      adiposity, independent of energy intake and expenditure. Advice encouraging
      drinking water and food moisture intake may be beneficial in addition to energy
      balance advice, in combating obesity.

PMID- 29600327
TI  - The histamine H4 receptor modulates the differentiation process of human monocyte
      derived M1 macrophages and the release of CCL4/MIP-1beta from fully
      differentiated M1 macrophages.
AB  - OBJECTIVE: Histamine is an important mediator of biological functions and present
      in high amounts in inflammatory skin lesions which are characterised by a marked
      infiltration of myeloid derived cell populations. The aim of the study was to
      investigate the expression and function of histamine receptors, with a focus on
      the histamine H4 receptor (H4R) in detail during the differentiation process from
      monocytes to macrophages and on fully differentiated M1 macrophages. METHODS:
      Quantitative PCR, ELISA technique, and flow cytometry were applied to analyze
      expression levels of histamine receptors, of CXCL10, CCL4, CCL3, or IL-23 and of
      the macrophage differentiation marker CD68, respectively. RESULTS: We
      demonstrated that monocytes and fully differentiated M1 macrophages express H1R-,
      H2R-, and H4R mRNA which were differentially regulated during the differentiation
      process and in IFN-Y and LPS classically activated M1 macrophages. The H3R mRNA
      was not expressed. During in vitro differentiation from monocytes to macrophages,
      the H4R agonist ST-1006 modified the M1 phenotype by up-regulating the macrophage
      differentiation marker CD68, by down-regulating the production of CXCL10, and by
      changing the morphology. In fully differentiated M1 macrophages, histamine or ST
      1006 decreased the IFN-Y- and LPS-induced CCL4 mRNA expression and protein
      production, whereas CCL3 or IL-23 production was not regulated via H4R.
      CONCLUSIONS: We describe novel immunomodulatory functions of the H4R during the
      differentiation process of human monocyte-derived macrophages and in fully
      differentiated M1 macrophages. The down-regulation of Th1-related chemokines
      during the differentiation process or in classically activated macrophages via
      H4R may contribute to decreased migration of immune cells to the site of
      inflammation. This may have implications for the treatment of allergic diseases
      with H4R ligands regulating the dysbalance of Th2/Th1 polarizations in these
      disorders.

PMID- 29600329
TI  - Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway
      inflammation.
AB  - BACKGROUND: Wheat amylase trypsin inhibitors (ATI) are dietary non-gluten
      proteins that activate the toll-like receptor 4 on myeloid cells, promoting
      intestinal inflammation. AIM OF THE STUDY: We investigated the effects of dietary
      ATI on experimental allergic airway inflammation. METHODS: Mice on a gluten and
      ATI-free diet (GAFD), sensitized with PBS or ovalbumin (OVA) and challenged with
      OVA, were compared to mice on a commercial standard chow, a gluten diet naturally
      containing ~ 0.75% of protein as ATI (G+AD), a gluten diet containing ~ 0.19% of
      protein as ATI (G-AD) and a GAFD with 1% of protein as ATI (AD). Airway
      hyperreactivity (AHR), inflammation in bronchoalveolar lavage (BAL) and pulmonary
      tissue sections were analyzed. Allergic sensitization was assessed ex vivo via
      proliferation of OVA-stimulated splenocytes. RESULTS: Mice on a GAFD sensitized
      with PBS did not develop AHR after local provocation with methacholine. Mice on a
      GAFD or on a G-AD and sensitized with OVA developed milder AHR compared to mice
      fed a G+AD or an AD. The increased AHR was paralleled by increased BAL
      eosinophils, IL-5 and IL-13 production, and an enhanced ex vivo splenocyte
      activation in the ATI-fed groups. CONCLUSIONS: Dietary ATI enhance allergic
      airway inflammation in OVA-challenged mice, while an ATI-free or ATI-reduced diet
      has a protective effect on AHR. Nutritional wheat ATI, activators of intestinal
      myeloid cells, may be clinically relevant adjuvants to allergic airway
      inflammation.

PMID- 29600332
TI  - Standards, innovations, and controversies in urologic imaging.

PMID- 29600331
TI  - Influence of fascicle length on twitch potentiation of the medial gastrocnemius
      across three ankle angles.
AB  - PURPOSE: Length dependence of post-activation potentiation (PAP) is a well
      established phenomenon in animal models but less certain in intact whole human
      muscles. Recent advances in B-mode ultrasonography provide real-time imaging and
      evaluation of human muscle fascicles in vivo, thus removing the assumption that
      joint positioning alters fascicle length and influences the extent of PAP. The
      purpose of this study was to determine whether a conditioning maximal voluntary
      contraction (MVC) would influence the return of medial gastrocnemius (MG)
      fascicles to baseline length and alter the extent of twitch potentiation between
      three ankle positions. METHODS: Ultrasonography was used to measure MG fascicle
      length for baseline and potentiated twitches at angles of 10 degrees 
      dorsiflexion (DF), 0 degrees  neutral (NEU-tibia perpendicular to the sole of the
      foot), and 20 degrees  plantar flexion (PF). A MVC was used as a conditioning
      contraction and PAP determined for each ankle angle. RESULTS: PAP of the plantar
      flexors was greater in PF (28.8 +/- 2.6%) compared to NEU (19.8 +/- 1.8%; p <
      0.05) and DF (9.3 +/- 2.8%; p < 0.0001). In PF, fascicle lengths (4.64 +/- 0.17
      cm) were shorter than both NEU (5.78 +/- 0.15 cm; p < 0.0001) and DF (6.09 +/-
      0.15 cm; p < 0.0001). Fascicle lengths for the baseline twitches were longer
      (5.92 +/- 0.11 cm) than the potentiated twitches (5.83 +/- 0.10 cm; p < 0.01) at
      all joint angles. CONCLUSION: Although PAP is greatest in PF compared to NEU and
      DF, the higher PAP in the PF joint angle cannot be attributed to fascicles
      remaining shortened following the MVC because across all joint positions,
      fascicles are similarly shortened following the MVC.

PMID- 29600330
TI  - Measuring the Impact of Gastrointestinal Variables on the Systemic Outcome of Two
      Suspensions of Posaconazole by a PBPK Model.
AB  - For the last two decades, the application of physiologically based
      pharmacokinetic (PBPK) models has grown exponentially in the field of oral
      absorption and in a regulatory context. Although these models are widely used,
      their predictive power should be validated and optimized in order to rely on
      these models and to know exactly what is going on "under the hood". In this
      study, an automated sensitivity analysis (ASA) was performed for 11
      gastrointestinal (GI) variables that are integrated into the PBPK software
      program Simcyp(r). The model of interest was a previously validated workspace
      that was able to predict the intraluminal and systemic behavior of two different
      suspensions of posaconazole in the Simcyp(r) Simulator. The sensitivity of the
      following GI parameters was evaluated in this model: gastric and duodenal pH,
      gastric and duodenal bicarbonate concentrations (reflecting buffer capacity),
      duodenal bile salts concentration, gastric emptying, the interdigestive migrating
      motor complex (IMMC), small intestinal transit time (SITT), gastric and jejunal
      volumes, and permeability. The most sensitive parameters were gastric/duodenal pH
      and gastric emptying, for both suspensions. The outcome of the sensitivity
      analyses highlights the important GI variables that must be integrated into an in
      vivo predictive dissolution test to help and create a rational and scientific
      framework/design for product development of novel and generic drug products.

PMID- 29600333
TI  - Predictors of surgical intervention following initial surveillance for acute
      ureteric colic.
AB  - PURPOSE: To identify clinical and stone-related factors predicting the need for
      surgical intervention in patients who were clinically considered appropriate for
      non-surgical intervention. PATIENTS AND METHODS: We conducted a retrospective
      review of a contemporary cohort of patients who were selected for surveillance
      following presentation with acute ureteric colic. Data on patient demographic and
      stone variables, inpatient management and long-term outcomes were evaluated.
      Multivariate logistic regression was used to generate a nomogram predicting need
      for surgical intervention. The accuracy of the nomogram was subsequently
      validated with an independent cohort of patients presenting with ureteric colic.
      RESULTS: Of 870 study eligible patients presenting with acute ureteric colic, 527
      were initially treated non-surgically and included in the analysis. 113 of these
      eventually required surgical intervention. Median time from first presentation to
      acute surgery was 11 (IQR 4-82) days. In our final MVA analysis, duration of
      symptoms more than 3 days, not receiving alpha-blockers, positive history of
      previous renal calculi and stone location, burden and density were independent
      predictors of need for surgical intervention. Patients who required opioid
      analgesia were more likely to have surgical intervention; however, this did not
      reach statistical significance. The area under the curve (AUC) of the final model
      was 0.802. The nomogram was validated with a cohort of 210 consecutive colic
      patients with AUC of 0.833 (SE 0.041, p < 0.001). CONCLUSIONS: We have identified
      independent predictors of the need for surgical intervention during an episode of
      renal colic and formulated a nomogram. Combined with the diligent use of acute
      ureteroscopy at our centre, this nomogram may have clinical utility when making
      decisions regarding treatment options with potential healthcare cost savings.

PMID- 29600334
TI  - Supra-pubic versus urethral catheter after robot-assisted radical prostatectomy:
      systematic review of current evidence.
AB  - PURPOSE: To provide latest evidence on the use of suprapubic catheter (SPC)
      versus urethral catheter (UC) after robot-assisted laparoscopic radical
      prostatectomy (RARP). MATERIALS AND METHODS: A systematic revision of literature
      was performed up to September 2017 using different search engines (Pubmed, Ovid,
      Scopus) to identified studies comparing the use of SPC versus standard UC after
      RARP. Identification and selection of the studies were conducted according to the
      preferred reporting items for systematic reviews and meta-analysis criteria. For
      continuous outcomes, the weighted mean difference (WMD) was used as a summary
      measure, whereas the odds ratio (OR) or risk ratio (RR) with 95% confidence
      interval (CI) was calculated for binary variables. RR was preferred in cases of a
      high number of events to avoid overestimation. Pooled estimates were calculated
      using the random-effect model to account for clinical heterogeneity. All
      statistical analyses were performed using Review manager 5 (Cochrane
      Collaboration, Oxford, UK). RESULTS: Eight studies were identified and included
      in this systematic review, namely 3 RCTs, 4 non-randomized prospective studies,
      and one retrospective study. A total of 966 RARP cases were collected for the
      cumulative analysis. Among them, 492 patients received standard UC and 474 SPC
      placement after RARP. UC patients had higher baseline PSA (WMD 0.44 ng/ml; p =
      0.02). Visual Analog Scale (VAS) score was found to be significantly lower in
      patients with SPC at postoperative day 7 (WMD 0.53; 95% CI 0.13-0.93; p = 0.009).
      Regarding penile pain, a significant difference in favor of the SPC group was
      found at postoperative day 7 assessment (WMD 1.2; 95% CI 0.82-1.6; p < 0.001).
      More patients in the SPC group reported "not at all" or "minimal pain" at this
      time point (OR 0.17, 95% CI 0.06, 0.44; p < 0.001). No significant differences
      were found in terms of continence recovery rate at 6-12 weeks between the groups
      (UC 78.7%, 88.2%; RR 0.92, 95% CI 0.84, 1.01; p = 0.09). Similarly, no
      differences were found in terms of catheter-related issues (p = 0.17). However,
      UC patients had lower likelihood of overall complications (OR 0.44, 95% CI 0.21
      0.89, p = 0.02). CONCLUSIONS: Available evidence suggests that the use of SPC can
      be a viable option for postoperative urine drainage after RARP, as it can
      translate into decreased postoperative pain without carrying a significant higher
      risk of catheter-related complications. Further investigation seems to be
      warranted, ideally within the framework of a multicentre randomized study with
      standardized analysis of outcomes.

PMID- 29600335
TI  - Radiation exposure for intraoperative 3D scans in a hybrid operating room: how to
      reduce radiation exposure for the surgical team.
AB  - BACKGROUND: Hybrid operating rooms are used in different fields of surgery. In
      orthopedic surgery, the possibility of a 3D scan of difficult anatomical regions
      (spine, pelvis) showed promising results not only in navigated screw placement.
      The associated exposure to radiation raises questions regarding potential risks
      for the operating room personal and the patient. The present study focuses on
      scatter radiation during 3D scans in a hybrid operating room, the adjacent rooms,
      and methods to reduce radiation exposure. MATERIAL AND METHODS: [Formula: see
      text] i2 dosimeters were used to measure scatter radiation during 3D scans of
      different anatomical regions in different distances and heights in a hybrid
      operating room. The 3D scans were performed with a floor-based flat-panel robotic
      C-arm with 3D scan capability (Artis Zeego, Siemens; Germany). The 3D scans were
      performed using a human cadaver. The 3D scans were performed using a standard and
      a dose reduction protocol (DRP). RESULTS: The highest scatter radiation was
      measured during 3D scans of the pelvis on the side of the surgical assistant
      (39.5 uSv in height of 1 m) compared to the side of the main surgeon (23 uSv in
      height of 1 m). Scatter radiation was less on the position of the scrub nurse
      (6.8 uSv in height of 1 m) and during 3D scans of the other anatomical regions.
      The radiation dosage was about 66% less with the DRP. Low values of scatter
      radiation were measured behind a radiation protection wall and with open doors in
      the adjacent rooms. CONCLUSION: While performing a scan scatter radiation was
      measured everywhere in the operating room especially during 3D scans of the
      pelvic girdle. Therefore, settings with lower dosage should be used whenever
      possible. Personnel should stand behind a radiation safety wall or leave the
      operating room and close the doors. For this study, six behavioral rules to avoid
      radiation in a hybrid operating room were established.

PMID- 29600336
TI  - [Atrial fibrillation as a comorbidity of heart failure].
AB  - Atrial fibrillation and heart failure are diseases that frequently occur together
      in patients, and the prevalence of the two diseases will continue to increase in
      the future. Unfortunately, they exacerbate each other: the prognosis of patients
      with atrial fibrillation is poorer if there is heart failure, and the prognosis
      of heart failure patients with atrial fibrillation is poorer than the prognosis
      of heart failure patients without atrial fibrillation. In the past, studies on
      drug stabilization of sinus rhythm with antiarrhythmic drugs were not able to
      show any influence on the prognosis of patients. In these patients, it seems to
      be better to treat the atrial fibrillation interventionally. The CASTLE-AF study
      has just shown for the first time that isolation of the pulmonary vein to treat
      atrial fibrillation in heart failure patients has positive effects: hospital
      admissions for heart failure decreased and the overall survival improved. Further
      studies have shown that quality of life improves and performance is increased.

PMID- 29600337
TI  - Mutations in Smad-interacting protein 1 gene are responsible for absence of its
      expression in Hirschsprung's disease.
AB  - Hirschsprung's disease (HSCR) is a common congenital malformation of the enteric
      nervous system. The pathophysiological basis remains unclear. Recently, the SIP1
      gene has been recognized as being involved in the pathogenesis of symptomatic
      HSCR patients with 2q22 chromosomal rearrangement. In this study, mutations in
      SIP1 were analyzed to explore the relationship between SIP1 and HSCR. All exons
      of SIP1 were amplified and then analyzed by PCR-restriction fragment length
      polymorphism (PCR-RFLP) and DNA sequencing. SIP1 expression was determined by
      immunohistochemistry, Western blot and real-time quantitative PCR. By PCR-RFLP,
      three different electrophoretic bands of 536, 428 and 257 bp representing
      different genotypes were demonstrated accordingly. DNA sequencing revealed a
      heterozygous absence of codon 157 GTG -> GTA exchange at exon 7. Simultaneously,
      exchanges of GCC -> ACC at codon 351 and ACC -> GCC at codon 395 were also
      observed in exon 8. All the exchanges caused a missense mutation. By
      immunohistochemistry, SIP1 was ectopically expressed in the aganglionic segment
      of HSCR without mutation. For comparison, in HSCR with mutation either in exon 7
      or exon 8, SIP1 immunoreactivity disappeared in all structures. The protein and
      mRNA levels determined by Western blot and real-time quantitative PCR were
      consistent with that of immunohistochemistry. In summary, mutations of the SIP1
      gene were detected in HSCR. These mutations in SIP1 were responsible for the
      absence of its expression in HSCR and contributed to the pathogenesis of this
      disease.

PMID- 29600338
TI  - Reply to "Pain Control After Bariatric Surgery: We Still Need More Answers".

PMID- 29600339
TI  - Mini Gastric Bypass-One Anastomosis Gastric Bypass (MGB-OAGB)-IFSO Position
      Statement.
AB  - PREAMBLE: The International Federation for the Surgery of Obesity and Metabolic
      Disorders (IFSO) has played an integral role in educating both the metabolic
      surgical and the medical community at large about the role of innovative and new
      surgical and/or endoscopic interventions in treating adiposity-based chronic
      diseases.The mini gastric bypass is also known as the one anastomosis gastric
      bypass. The IFSO has agreed that the standard nomenclature should be the mini
      gastric bypass-one anastomosis gastric bypass (MGB-OAGB). The IFSO commissioned a
      task force (Appendix 1) to determine if MGB-OAGB is an effective and safe
      procedure and if it should be considered a surgical option for the treatment of
      obesity and metabolic diseases.The following position statement is issued by the
      IFSO MGB-OAGB task force and approved by the IFSO Scientific Committee and
      Executive Board. This statement is based on current clinical knowledge, expert
      opinion, and published peer-reviewed scientific evidence. It will be reviewed in
      2 years.

PMID- 29600341
TI  - Fever Burden and Health-Related Quality of Life After Intracerebral Hemorrhage.
AB  - BACKGROUND: Fever is associated with worse functional outcomes after
      intracerebral hemorrhage (ICH); however, there are few prospective data to
      quantify the relationship with health-related quality of life (HRQoL). We tested
      the hypothesis that increased burden of fever is independently associated with
      decreased HRQoL at follow-up. METHODS: In this prospective observational cohort
      study of 106 ICH patients admitted to a tertiary care hospital between 2011 and
      2015, we recorded the highest core temperature each calendar day for 14 days
      after ICH onset. Fever burden was defined as the number of days with a fever >=
      100.4  degrees F (38  degrees C). HRQoL outcomes were measured with Neuro-QoL
      domains of Cognitive Function and Mobility at 28 days, 3 months, and 1 year.
      Results were analyzed using mixed effects regression analysis. RESULTS: Each
      additional day with a fever was independently associated with lower Mobility
      HRQoL (T-score - 0.9, [- 1.6 to - 0.2]; p = 0.01) and Cognitive Function HRQoL (T
      score - 1.3 [- 2.0 to - 0.6]; p = 0.001) after correction for National Institutes
      of Health Stroke Scale score on admission, age, and time to follow-up.
      CONCLUSIONS: Each additional day with a fever was predictive of worse HRQoL
      domains of Cognitive Function and Mobility after ICH up to 1 year. These data
      extend previous evidence on the negative association of fever and functional
      outcomes to the domains of Cognitive Function and Mobility HRQoL. HRQoL outcomes
      may be a sensitive and powerful way to measure the efficacy of fever control in
      future research.

PMID- 29600340
TI  - The effect of hot days on occupational heat stress in the manufacturing industry:
      implications for workers' well-being and productivity.
AB  - Climate change is expected to exacerbate heat stress at the workplace in
      temperate regions, such as Slovenia. It is therefore of paramount importance to
      study present and future summer heat conditions and analyze the impact of heat on
      workers. A set of climate indices based on summer mean (Tmean) and maximum (Tmax)
      air temperatures, such as the number of hot days (HD: Tmax above 30  degrees C),
      and Wet Bulb Globe Temperature (WBGT) were used to account for heat conditions in
      Slovenia at six locations in the period 1981-2010. Observed trends (1961-2011) of
      Tmean and Tmax in July were positive, being larger in the eastern part of the
      country. Climate change projections showed an increase up to 4.5  degrees C for
      mean temperature and 35 days for HD by the end of the twenty-first century under
      the high emission scenario. The increase in WBGT was smaller, although
      sufficiently high to increase the frequency of days with a high risk of heat
      stress up to an average of a third of the summer days. A case study performed at
      a Slovenian automobile parts manufacturing plant revealed non-optimal working
      conditions during summer 2016 (WBGT mainly between 20 and 25  degrees C). A
      survey conducted on 400 workers revealed that 96% perceived the temperature
      conditions as unsuitable, and 56% experienced headaches and fatigue. Given these
      conditions and climate change projections, the escalating problem of heat is
      worrisome. The European Commission initiated a program of research within the
      Horizon 2020 program to develop a heat warning system for European workers and
      employers, which will incorporate case-specific solutions to mitigate heat
      stress.

PMID- 29600342
TI  - Hemodynamic Therapy for Delayed Cerebral Ischemia in SAH.

PMID- 29600343
TI  - Medulla Oblongata Hemorrhage and Takotsubo Syndrome: Any Advantages from
      Monitoring Cardiac Autonomic Adrenergic Surges?

PMID- 29600344
TI  - Size Matters: Metastatic Cluster Size and Stromal Recruitment in the
      Establishment of Successful Prostate Cancer to Bone Metastases.
AB  - Prostate cancer (PCa) impacts over 180,000 men every year in the USA alone, with
      26,000 patients expected to succumb to the disease ( cancer.gov ). The primary
      cause of death is metastasis, with secondary lesions most commonly occurring in
      the skeleton. Prostate cancer to bone metastasis is an important, yet poorly
      understood, process that is difficult to explore with experimental techniques
      alone. To this end we have utilized a hybrid (discrete-continuum) cellular
      automaton model of normal bone matrix homeostasis that allowed us to investigate
      how metastatic PCa can disrupt the bone microenvironment. Our previously
      published results showed that PCa cells can recruit mesenchymal stem cells (MSCs)
      that give rise to bone-building osteoblasts. MSCs are also thought to be
      complicit in the establishment of successful bone metastases (Lu, in Mol Cancer
      Res 4(4):221-233, 2006). Here we have explored the aspects of early metastatic
      colonization and shown that the size of PCa clusters needs to be within a
      specific range to become successfully established: sufficiently large to maximize
      success, but not too large to risk failure through competition among cancer and
      stromal cells for scarce resources. Furthermore, we show that MSC recruitment can
      promote the establishment of a metastasis and compensate for relatively low
      numbers of PCa cells seeding the bone microenvironment. Combined, our results
      highlight the utility of biologically driven computational models that capture
      the complex and dynamic dialogue between cells during the initiation of active
      metastases.

PMID- 29600345
TI  - Tips and Tricks for a Laparoscopic Approach to Paracaval Liver Segments.
AB  - BACKGROUND: A dramatic spread of laparoscopic liver surgery has been experienced
      over the last years. The approach to paracaval liver segments 1 and 9 is still
      poorly described in literature, mainly due to its technical demands. OBJECTIVE:
      The aim of this article was to introduce a safe and effective approach to
      paracaval liver segments through laparoscopy. METHODS: A minimally invasive
      approach to resection of Segments 1 and 9 is presented, and an operative set-up
      is depicted. A step-by-step technique describing the inferior vena cava (IVC)
      with left and right hepatic venous junction exposure, segmental pedicle
      isolation, and parenchymal transection is shown through a video document.
      RESULTS: Postoperative courses were uneventful, and patients were discharged on
      postoperative day 3. DISCUSSION: The approach to paracaval liver segments
      requires accurate preoperative case selection, technical, surgical, and
      anesthesiological expertise in laparoscopic liver surgery, and adequate
      instrumentary. CONCLUSION: Paracaval segments of the liver can be approached
      safely through laparoscopy by teams with extensive expertise in the field of
      laparoscopic liver surgery; however, suspected malignant infiltration of the IVC
      or unclear preoperative anatomy still contraindicate this approach.

PMID- 29600346
TI  - Delays in Adjuvant Chemotherapy Among Breast Cancer Patients: An Unintended
      Consequence of Breast Surgery?

PMID- 29600347
TI  - Academic Surgical Oncologists' Productivity Correlates with Gender, Grant
      Funding, and Institutional NCI Comprehensive Cancer Center Affiliation.
AB  - BACKGROUND: A scholar's h-index is defined as the number of h papers published,
      each of which has been cited at least h times. We hypothesized that the h-index
      strongly correlates with the academic rank of surgical oncologists. METHODS: We
      utilized the National Cancer Institute (NCI) website to identify NCI-designated
      Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked
      general surgery residency programs with surgical oncology divisions. Demographic
      data of respective academic surgical oncologists were collected from departmental
      websites and Grantome. Bibliometric data were obtained from Web of Science.
      RESULTS: We identified 544 surgical oncologists from 64 programs. Increased h
      index was associated with academic rank (p < 0.001), male gender (p < 0.001),
      number of National Institutes of Health (NIH) grants (p < 0.001), and affiliation
      with an NCI CCC (p = 0.018) but not number of additional degrees (p = 0.661) or
      Doximity ranking (p = 0.102). H-index was a stronger predictor of academic rank
      (r = 0.648) than total publications (r = 0.585) or citations (r = 0.450).
      CONCLUSIONS: This is the first report to assess the h-index within academic
      surgical oncology. H-index is a bibliometric predictor of academic rank that
      correlates with NIH grant funding and NCI CCC affiliation. We also highlight a
      previously unexpected and unappreciated gender disparity in the academic
      productivity of US surgical oncologists. When academic rank was accounted for,
      female surgical oncologists had lower h-indices compared with their male
      colleagues. Evaluation of the etiologies of this gender disparity is needed to
      address barriers to academic productivity faced by female surgical oncologists as
      they progress through their careers.

PMID- 29600348
TI  - Analysis of symmetry between lower limbs during gait of older women with
      bilateral knee osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a common condition in older adults, with high
      epidemiological, clinical, and economic burden worldwide. In clinical practice,
      patients with knee OA often walk with abnormal gait patterns because of pain,
      stiffness and/or mobility dysfunctions. Therefore, assessing the symmetry of the
      lower limbs might improve the rehabilitation treatment and prescription of
      walking devices. AIMS: To compare the symmetry of step length and single support
      phase between lower limbs during gait of older women with bilateral knee OA and
      asymptomatic controls, and to verify if there is difference between these two
      groups in relation to velocity, cadence, step length and single support phase.
      METHODS: This cross-sectional study included a convenience sample of 66 community
      dwelling older women aged >= 65 years with a medical diagnosis of symptomatic
      bilateral knee OA (n = 33) and asymptomatic controls (n = 33), matched by age and
      body mass index. All gait parameters were obtained using the GAITRite(r) system.
      RESULTS: Mean age of the sample was 72.6 +/- 4.0 years. Participants with OA
      walked with lower velocity (p = 0.001), cadence (p = 0.009) and step length
      bilaterally (both p = 0.001). No significant difference was found between groups
      in the symmetry of step length between lower limbs, single support phase and
      symmetry of single support phase between lower limbs. CONCLUSION: Older women
      with bilateral knee OA walk with lower velocity, cadence and step length, but
      have the same symmetry in the step length and single support phase between lower
      limbs as asymptomatic older women.

PMID- 29600349
TI  - Delivery of Brain-Derived Neurotrophic Factor by 3D Biocompatible Polymeric
      Scaffolds for Neural Tissue Engineering and Neuronal Regeneration.
AB  - Biopolymers are increasingly employed for neuroscience applications as scaffolds
      to drive and promote neural regrowth, thanks to their ability to mediate the
      upload and subsequent release of active molecules and drugs. Synthetic degradable
      polymers are characterized by different responses ranging from tunable distension
      or shrinkage to total dissolution, depending on the function they are designed
      for. In this paper we present a biocompatible microfabricated poly-epsilon
      caprolactone (PCL) scaffold for primary neuron growth and maturation that has
      been optimized for the in vitro controlled release of brain-derived neurotrophic
      factor (BDNF). We demonstrate that the designed morphology confers to these
      devices an enhanced drug delivery capability with respect to monolithic
      unstructured supports. After incubation with BDNF, micropillared PCL devices
      progressively release the neurotrophin over 21 days in vitro. Moreover, the
      bioactivity of released BDNF is confirmed using primary neuronal cultures, where
      it mediates a consistent activation of BDNF signaling cascades, increased
      synaptic density, and neuronal survival. These results provide the proof-of
      principle on the fabrication process of micropatterned PCL devices, which
      represent a promising therapeutic option to enhance neuronal regeneration after
      lesion and for neural tissue engineering and prosthetics.

PMID- 29600351
TI  - A Digital Language Divide? The Relationship between Internet Medication Refills
      and Medication Adherence among Limited English Proficient (LEP) Patients.
AB  - BACKGROUND: Use of an Internet portal to refill medicines positively affects
      medication adherence among English-speakers. No prior studies, however, have
      specifically examined the relationship between Internet refills and medication
      adherence among patients who are limited English proficient (LEP). OBJECTIVES:
      (1) Examine the relationship between Internet medication refill system use and
      medication adherence among linguistically diverse patients with chronic
      conditions and (2) compare this relationship between LEP and English-proficient
      (EP) patients. DESIGN, PARTICIPANTS, MEASURES: We analyzed 2013-2014 cross
      sectional data from 509 surveyed adults in the Group Health Cooperative. Surveys
      were merged with plan enrollment, claims data, and electronic medical records.
      Medication adherence was calculated by the "Continuous Measure of Medication
      Gaps" (CMG) method. For Internet refill system use, patients were asked, "Have
      you used the health systems Internet site to refill any medications in the last
      12 months?" LEP status was captured in the electronic medical record by a non
      English primary language and a claims record of interpreter use in at least one
      clinical encounter between 2005 and 2012. We used multivariate linear regression
      models to examine Internet refill system use and medication adherence and
      compared the association between LEP and EP patients. RESULTS: Three hundred
      eighty-four patients (75%) had a calculable CMG: 134 EP and 250 LEP in the
      adherence analyses. In unadjusted analyses, LEP patients had lower use of the
      Internet refill system (p < .001) and lower adherence versus the EP group (p <
      .001). In multivariate analyses, LEP status (beta = - 0.022, p = .047) was
      negatively associated with adherence, while use of the Internet refill system
      (beta = 0.030, p = .002) was positively associated. In stratified models, use of
      Internet refills was positively associated with adherence, even when examining
      LEP (beta = 0.029, p = .003) and EP patients (beta = 0.027, p = .049) separately.
      CONCLUSIONS: These findings suggest that LEP patients may be under-utilizing a
      beneficial Internet tool. Should our healthcare systems fail to ensure that LEP
      patients have full and meaningful access to Internet patient portals, we risk
      worsening healthcare disparities.

PMID- 29600352
TI  - Ethnic Disparity in Annual Healthcare Expenditures for Type 2 Diabetes Mellitus
      in Ningxia, China.
AB  - BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) and its
      complications has been increasing worldwide with an increasing provision of long
      term medications and health services. This study aimed to assess the healthcare
      costs for T2DM patients for vulnerable ethnic minority. METHODS: A cross
      sectional study was conducted from October 13, 2016, to June 19, 2017, in two
      public hospitals in Ningxia, China. Eligible Hui and Han inpatients were
      recruited and interviewed. Ethnic disparities in annual healthcare expenditures
      for T2DM measured from a societal perspective and its associations of
      expenditures with other factors were analyzed by linear and quantile regressions.
      RESULTS: Ethnic disparities in annual healthcare expenditures for T2DM were
      demonstrated, mainly reflecting differences in the cost of productivity loss. The
      quantile of annual healthcare expenditure showed significant ethnic disparities
      in T2DM patients with complications. At the 10th to 50th quantiles of healthcare
      expenditures, Hui patients had significantly lower expenditures than Han patients
      in both unadjusted and adjusted models. Non-significant difference in
      expenditures between Hui and Han patients was found at the 90th quantile of
      expenditure in the unadjusted model, but significantly higher expenditures for
      Hui patients were shown when adjusted for socioeconomic and clinical factors.
      CONCLUSION: T2DM Hui patients faced significantly higher expenditures than Han
      patients when the costs of healthcare were high. Appropriate national policy
      considering the issue of ethnic minority should be further explored to improve
      health and subsidize economic burden for T2DM patients.

PMID- 29600353
TI  - The Variants in the 3' Untranslated Region of the Matrix Metalloproteinase 9 Gene
      as Modulators of Treatment Outcome in Children with Asthma.
AB  - PURPOSE: The maintaining of asthma control is difficult due to high variability
      in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is
      implicated in inflammation and remodeling of asthmatic airways, it could be
      associated with adequate response to asthma therapy. The aim of this study was to
      investigate whether variants in 3' end of the MMP9 gene are associated with
      clinical phenotype and responsiveness to treatment in children with asthma.
      METHODS: The study included 127 asthmatic children from Slovenia. Variants in the
      3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained
      results were correlated with clinical parameters. RESULTS: Two variants were
      detected, rs13925 and rs20544. For the variant rs20544, statistically significant
      difference in airway hyperresponsiveness (p = 0.011) and asthma control (p =
      0.049) between genotypes was found. Patients with TT genotype had lower airway
      sensitivity, and after 12 months of treatment showed significant improvement in
      Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant
      rs13925, the association with lung function was observed. The carriers of A
      allele showed noticeable improvement of lung function after the first 6 months of
      treatment in comparison to the carriers of G allele (p = 0.046). CONCLUSION: The
      main finding of our study is the association of MMP9 genotypes rs20544 TT and
      rs13925 AA and AG with better asthma control, and indirectly better response to
      treatment. Based on these results, MMP9 deserves further research as a potential
      predictive biomarker for asthma.

PMID- 29600350
TI  - Adrenomedullin, a Novel Target for Neurodegenerative Diseases.
AB  - Neurodegenerative diseases represent a heterogeneous group of disorders whose
      common characteristic is the progressive degeneration of neuronal structure and
      function. Although much knowledge has been accumulated on the pathophysiology of
      neurodegenerative diseases over the years, more efforts are needed to understand
      the processes that underlie these diseases and hence to propose new treatments.
      Adrenomedullin (AM) is a multifunctional peptide involved in vasodilation,
      hormone secretion, antimicrobial defense, cellular growth, and angiogenesis. In
      neurons, AM and related peptides are associated with some structural and
      functional cytoskeletal proteins that interfere with microtubule dynamics.
      Furthermore, AM may intervene in neuronal dysfunction through other mechanisms
      such as immune and inflammatory response, apoptosis, or calcium dyshomeostasis.
      Alterations in AM expression have been described in neurodegenerative processes
      such as Alzheimer's disease or vascular dementia. This review addresses the
      current state of knowledge on AM and its possible implication in
      neurodegenerative diseases.

PMID- 29600354
TI  - Nutritional profile of patients with chronic inflammatory diseases in the age of
      biologicals.
AB  - Tumor necrosis factor alpha (TNFalpha) has an important role in the body
      composition of patients with rheumatoid arthritis (RA), Crohn's disease (CD), and
      spondyloarthritis (SpA). We aimed to assess the nutritional profile of patients
      with RA, CD, and SpA undergoing remission with multiple therapies comparing to
      controls and to analyze the effect of anti-TNFalpha medications in the
      nutritional parameters of these patients. One hundred thirty-one patients were
      included: 44 with RA, 43 with CD, and 44 with SpA. Patients receiving anti
      TNFalpha were compared with those receiving non-biological treatment as well as
      to controls. Nutritional profile included body mass index (BMI), waist
      circumference (WC), mid-upper arm circumference, and triceps skinfold
      measurement. Overweight and obesity were highly prevalent on three assessed
      groups. In patients with RA, BMI was > 25 kg/m2 in 74.9% patients and 49.2%
      controls (p < 0.0005); in CD, in 55.7% patients and 41.2% controls (p < 0.0001);
      and in SpA, in 68.1% patients and 43.5% controls (p < 0.0001). Central obesity
      was higher in all three disease groups when compared to healthy controls. There
      was no significant difference on nutritional parameters in patients using or not
      using anti-TNFalpha medications, except in patients with SpA, in which biologic
      therapy was significantly associated with lower BMI and WC, when compared to
      other therapies. Overweight, obesity, and elevated WC were more prevalent in
      patients with RA, CD, and SpA undergoing remission when compared to controls
      despite of used therapy. The use of biologic drugs in patients with SpA was
      associated with a lower BMI and lower WC.

PMID- 29600355
TI  - Introduction: Esophageal Adenocarcinoma: Updates of Current Status.
AB  - Esophageal and esophagogastric adenocarcinoma is highly prevalent in the Western
      populations and is a major cause of cancer-related morbidity and mortality
      worldwide. The incidence of esophageal adenocarcinoma is rapidly rising in the
      Western populations. The major predisposing diseases and pathogenesis (gastro
      esophageal reflux disease, Barrett esophagus, and dysplasia) of the cancer are
      well known. There is an urgent need for works of the multidisciplinary teams
      (clinical, pathological, the molecular biology and translational research) for
      improved outcomes of patients with this cancer.

PMID- 29600356
TI  - Radiotherapy for Esophageal Adenocarcinoma.
AB  - Adenocarcinomas occur in distal esophagus and often involve esophagogastric
      junction. Radiotherapy plays a key role in treatment, often in combination with
      chemotherapy and surgery in multi-modalities management. For resectable
      esophageal primaries, neoadjuvant chemoradiotherapy plus surgery can downstage
      disease and improve outcome over surgery alone. For patients with unresectable
      primaries or medically unfit for surgery, definitive chemoradiotherapy was found
      to improve survival over radiotherapy alone. For patients who had residual
      disease or involved margins after primary surgery, adjuvant chemoradiotherapy in
      postoperative setting was shown to improve local control and survival. Palliative
      radiotherapy can also be used to relieve local symptoms like dysphagia or
      bleeding. Careful radiotherapy planning is required to ensure adequate dose to
      target volumes without overdose to normal organs.

PMID- 29600357
TI  - Chemotherapy for Esophageal Adenocarcinoma.
AB  - Esophageal and esophagogastric junction adenocarcinoma is a distinct entity from
      esophageal squamous cell carcinoma with respect to etiology and biology despite
      sharing the same anatomical location. While most international treatment
      guidelines recommend a similar management strategy for both esophageal squamous
      and adenocarcinoma histologies, the evidence for treating adenocarcinoma are
      indeed more often extrapolated from that of gastric carcinoma. In this chapter,
      the best evidences for the management of this distinct disease with chemotherapy
      in both curative and palliative clinical settings are presented.

PMID- 29600358
TI  - Surgical Protocol for Esophageal Adenocarcinoma.
AB  - Esophagogastrectomy for esophageal adenocarcinoma remains a procedure of
      significant morbidity and mortality rates. Management should be within the
      context of a multidisciplinary team. Appropriate patient selection, careful
      preoperative preparation, meticulous application of surgical technique and
      perioperative care are essential for success. Enhanced recovery after surgery
      (ERAS) protocols are evidence based and improve outcome. Standard protocol for
      open transthoracic esophagectomy is described.

PMID- 29600359
TI  - Target Therapy for Esophageal Adenocarcinoma.
AB  - Adenocarcinoma of the esophagus is a deadly disease and median survival of
      patients with metastatic disease is around 1 year only. There is an unmet need to
      personalize treatment by identifying molecular targets and respective target
      therapy in esophageal adenocarcinoma. There has been success in targeting the
      human epidermal growth factor receptor 2 (HER2) and vasoendothelial growth factor
      (VEGF) pathway while more failures were encountered in the clinical studies
      targeting epidermal growth factor (EGFR), mammalian target of rapamycin (mTOR),
      and mesenchymal-epithelial transition (MET). Studies using immune-checkpoint
      inhibitors have shown early success, and we await mature data for clinical
      application. In the chapter, the target therapy and novel treatment strategy will
      be reviewed. In the future, it is hoped that advances in translational research
      in targeted therapy against esophageal adenocarcinoma will bring about new
      progress in clinical practice.

PMID- 29600360
TI  - Histopathological Assessment for Esophageal Adenocarcinoma.
AB  - In the World Health Organization (WHO) classification, adenocarcinoma of
      esophagus comprises preinvasive type (dysplasia), adenocarcinoma, adenoid cystic
      carcinoma, adenosquamous carcinoma, and mucoepidermoid carcinoma. For
      adenocarcinoma, it is important to determine the grading of the cancer and
      histological variants such as signet ring adenocarcinoma. In the current day
      management of esophageal adenocarcinoma by neoadjuvant therapy, the histology of
      the cancer and the lymph nodal status may change after the therapy. Tumor
      regression grading systems could be used to assess the response to the
      neoadjuvant therapy in esophageal adenocarcinoma.

PMID- 29600361
TI  - Macroscopic Assessment and Cut Up of Endoscopic Resection Specimens for Early
      Esophageal Glandular Malignancies.
AB  - Pathological assessment of tissue is the gold standard for diagnosis and staging
      of neoplasia and provides key prognostic information for clinical management.
      Proper macroscopic assessment and cut-up technique is essential to ensure that
      the overall assessment is correct and reproducible. Endoscopic mucosal resection
      is a technique used for removing early neoplastic glandular lesions of the
      esophagus at the level of submucosa. Here, we describe the macroscopic assessment
      and dissection techniques used for the routine handling of endoscopic mucosal
      resection specimens in the clinical laboratory.

PMID- 29600362
TI  - Processing of Surgical Specimen (Esophagogastrectomy) for Esophageal
      Adenocarcinoma.
AB  - An esophagogastrectomy is a surgical procedure that is performed for treatment of
      confirmed localized esophageal and esophagogastric junction adenocarcinoma.
      Proper macroscopic assessment and cut-up technique is essential to ensure that
      the overall assessment is correct and reproducible. Here, we describe a standard
      for macroscopic assessment and dissection to be used for routine handling of
      esophagogastrectomy specimens in the clinical laboratory.

PMID- 29600363
TI  - Application of Pathological Staging in Esophageal Adenocarcinoma.
AB  - Staging is one of the most important factors that determine the prognosis of the
      patients with esophageal adenocarcinoma. The current staging protocol includes
      parameters-extent of tumor (T), lymph node status (N), presence of distant
      metastasis (M), and grade of the adenocarcinoma (G). In addition, different
      criteria are used in patients with and without neoadjuvant therapy. The silent
      aspects of the use of new staging protocol are discussed.

PMID- 29600364
TI  - Application of Tissue Microarray in Esophageal Adenocarcinoma.
AB  - Tissue microarray technology could allow immunohistochemical staining or in situ
      hybridization on hundreds of different tissue samples simultaneously. It allows
      faster analysis and considerably reducing costs incurred in staining. The
      technique also provides a high-throughput analysis of multiple tissues for the
      different types of research. In the literature, many researches of esophageal
      adenocarcinoma use tissue microarray to enhance the output. In this chapter, we
      have a brief overview of tissue microarray technologies, the advantages and
      disadvantages of tissue microarray, and related troubleshootings.

PMID- 29600365
TI  - Predictive Marker: HER2 in Esophageal Adenocarcinoma.
AB  - HER2 positivity is based on the fundamental principle of amplification of the
      human epidermal growth factor receptor 2 (HER2) gene resulting in overexpression
      of the protein products . Arising from that a "HER2-positive cancer" is one that
      shows HER2 gene amplification and resultant protein expression as demonstrated by
      in situ hybridization and immunohistochemistry, respectively. Testing of the HER2
      status is crucial to ensure selection of the correct patient who may benefit from
      target therapy for esophageal adenocarcinoma. Accurate testing is dependent on
      several pre-analytical and analytical factors including sample selection,
      laboratory techniques, and accurate interpretation of HER2 test results.

PMID- 29600366
TI  - Whole-Slide Imaging for Esophageal Adenocarcinoma.
AB  - Whole-slide imaging revolutionizes the field of pathology especially in the areas
      of facilitation of research, long-term storages, exchange of information, and
      image analysis. In this process, a scanning equipment (scanner) scans the whole
      glass slide into a digital file. In research in esophageal adenocarcinoma or
      other cancers, whole-slide imaging could help in production of high-resolution
      images for studying and sharing of research information, assessment of tissue
      microarray slides as well as allowing digital image analysis of the tissue
      information such as level of staining (e.g., HER2) in a more efficient and
      objective manner. In this chapter, we will elaborate the concepts, advantages,
      barriers, and the operations of whole-slide imaging scanning.

PMID- 29600367
TI  - Animal Model: Reflux Models in Esophageal Adenocarcinoma.
AB  - Many mouse models have been developed to mimic the inflammation-metaplasia
      dysplasia-carcinoma sequence seen in the gastroesophageal reflux disease (GERD)
      Barrett's esophagus-esophageal adenocarcinoma progression. Surgical reflux models
      in mice are technically challenging due to the small size and intolerance to
      surgical stress of mice. Herein, we detail three representative surgical
      procedures that allow for creation of an esophageal adenocarcinoma model in mice,
      either with or without the use of carcinogens. Additionally, we describe a
      genetic model that shows spontaneous development of esophageal adenocarcinoma.

PMID- 29600368
TI  - Animal Model: Xenograft Mouse Models in Esophageal Adenocarcinoma.
AB  - Researchers often use murine models of esophageal cancer to evaluate novel
      therapies prior to clinical protocol treatment. Subcutaneous xenograft models are
      often used for testing the efficacy of anticancer agents in many cancers
      including esophageal adenocarcinoma. However, mice subcutaneous esophageal
      adenocarcinoma models only represent local tumor growth and do not provide any
      information about a survival benefit for a particular anticancer regimen, which
      is very crucial for experimental treatment efficacy. In addition, anticancer
      agents may well inhibit subcutaneous tumor growth without effecting overall
      animal survival. Herein, we describe a peritoneal dissemination mouse xenograft
      model for survival outcome analysis with intraperitoneal injection of human
      esophageal adenocarcinoma cell lines.

PMID- 29600369
TI  - Identification of Cancer Stem Cells in Esophageal Adenocarcinoma.
AB  - Cancer stem cells (CSCs) are a subpopulation of cancer cells that have the
      ability to self-renew and to generate differentiated cells of various lineages.
      Due to their specific morphological and biological features, they are often
      resistant to therapy and in turn lead to metastasis and cancer recurrence.
      Because of their crucial roles in carcinogenesis and patient prognosis,
      identification and isolation of CSCs have become an important part of improved
      cancer management regime. Isolation, characterization, and development of
      targeted therapy against CSCs have potential efficacy in treating esophageal
      cancer. In addition, CSCs can act as a predictive tool for chemoradiotherapy
      response in esophageal adenocarcinoma. Different methods including functional
      assays, cell sorting using various intracellular, and cell surface markers and
      xenotransplantation techniques are used for the identification and separation of
      CSCs in different cancers. None of these methods solely can guarantee complete
      isolation of CSC population, thus a combination of methods could be used for
      reliable detection and isolation of CSCs. Here, we describe the identification
      and isolation of CSCs from esophageal adenocarcinoma cells by cell sorting after
      Hoechst 33342 staining followed by in vitro functional assays, and in vivo
      xenograft techniques.

PMID- 29600370
TI  - Circulatory Tumor Cells in Esophageal Adenocarcinoma.
AB  - While circulating tumor cells (CTCs) within peripheral blood of cancer patients
      are no new phenomenon in many carcinomas, there is a lack of information on the
      biological and clinical implications of CTCs in esophageal adenocarcinomas.
      Limited evidence suggests that the CTCs are frequently detected in esophageal
      adenocarcinomas when compared to esophageal squamous cell carcinoma suggesting
      the potential difference in the pathogenesis between these two carcinomas. In
      addition, the varied CTC levels between adenocarcinoma and squamous cell
      carcinomas of the esophagus could be attributed to the varied expression pattern
      of epithelial markers such as epithelial cell adhesion molecule (EpCAM) and
      cytokeratin (CK). In esophageal adenocarcinomas, CTC levels correlated with
      pathological T stages, lymph node metastasis, and patient survival. Thus,
      detection of CTCs potentially acts as a noninvasive and real-time biomarker for
      predicting patient prognosis in esophageal adenocarcinomas. Although the CTC
      detection is currently performed using various methods, the only Food and Drug
      Administration (FDA) of USA approved CTC detection method in clinics is the
      CELLSEARCH(r) system. This chapter will discuss various biological
      characteristics of CTC and its potential implications in esophageal
      adenocarcinomas. In addition, a quick overview of CTC detection methodology is
      outlined.

PMID- 29600371
TI  - Liquid Biopsy for Investigation of Cancer DNA in Esophageal Adenocarcinoma: Cell
      Free Plasma DNA and Exosome-Associated DNA.
AB  - Liquid biopsy of cancers is an area of increasing interest in medical practice
      for the surveillance, management, and potential detection of malignant cells,
      using minimally invasive collection of body fluids. A liquid biopsy is
      particularly useful for metastatic cancers, which may be difficult to be sampled
      by core biopsy, due to difficulty of access or an occult location. Access to DNA
      shed from esophageal adenocarcinoma can enable the detection of mutations
      confirming the presence of malignant cells or the evolution of clonal lines with
      altered treatment response profiles. In this chapter, we detail a method for the
      isolation of cell-free DNA from blood plasma and DNA associated with exosomes in
      blood from patients with esophageal adenocarcinoma.

PMID- 29600372
TI  - Somatic DNA Copy-Number Alterations Detection for Esophageal Adenocarcinoma Using
      Digital Polymerase Chain Reaction.
AB  - Somatic copy-number alterations are commonly found in cancer and play key roles
      in activating oncogenes and deactivating tumor suppressor genes. Digital
      polymerase chain reaction is an effective way to detect the changes in copy
      number. In esophageal adenocarcinoma, detection of somatic copy-number
      alterations could predict the prognosis of patients as well as the response to
      therapy. This chapter will review the methods involved in digital polymerase
      chain reaction for the research or potential clinical applications in esophageal
      adenocarcinoma.

PMID- 29600374
TI  - DNA Genome Sequencing in Esophageal Adenocarcinoma.
AB  - Next-generation sequencing refers to the high-throughput DNA sequencing
      technologies, which are capable of sequencing large numbers of different DNA
      sequences in a single/parallel reaction. It is a powerful tool to identify
      inherited and acquired genetic alterations associated with the development of
      esophageal adenocarcinoma. Whole-genome sequencing is the most comprehensive but
      expensive, whereas whole-exome sequencing is cost-effective but it only works for
      the known genes. Thus, second-generation sequencing methods can provide a
      complete picture of the esophageal adenocarcinoma genome by detecting and
      discovering different type of alterations in the cancer. This would help in
      diagnostics and will further help in developing personalized medicine in
      esophageal adenocarcinoma.

PMID- 29600373
TI  - Targeted Single Gene Mutation in Esophageal Adenocarcinoma.
AB  - Esophageal adenocarcinoma is heterogeneous and studies have reviewed many
      important mutations that contribute to the pathogenesis of the cancer. These
      discoveries have helped paved the way into identifying new gene markers or gene
      targets to develop novel molecular directed therapy for better patient outcomes
      in esophageal adenocarcinoma. Despite the recent bloom in next-generation
      sequencing, Sanger sequencing still represents the gold standard method for the
      study of the driver genes in esophageal adenocarcinoma. This chapter focuses on
      the sequencing techniques in identification of single gene mutations.

PMID- 29600375
TI  - Epigenetics: DNA Methylation Analysis in Esophageal Adenocarcinoma.
AB  - The aberrant DNA methylation has been noted to occur at promoter of tumor
      suppressor, cell adhesion, DNA repair, and other growth regulating genes during
      the progression of nonneoplastic esophageal mucosa to Barrett esophagus to
      esophageal adenocarcinoma. Methylation-mediated silencing of individual gene or
      concurrent loss of a number of genes plays crucial roles in dysplasia-metaplasia
      neoplasia sequence of esophageal adenocarcinoma. In addition, promoter
      methylation of genes had shown significant prognostic potential in patients with
      esophageal adenocarcinoma. Thus, determination of methylation status of genes of
      interest can be used as a molecular marker for risk stratification and/or better
      prognosis of patients with esophageal adenocarcinoma. There are a number of
      methods including bead array, PCR and sequencing, pyrosequencing, methylation
      specific PCR, and PCR with high-resolution melt curve available to determine the
      methylation status of particular gene of interest. Herein, we describe the
      polymerase chain reaction followed by sequencing-based protocol for identifying
      DNA methylation status in esophageal adenocarcinoma.

PMID- 29600376
TI  - Detection and Quantification of MicroRNAs in Esophageal Adenocarcinoma.
AB  - MicroRNAs (miRNAs) are a class of small, noncoding RNAs that have been emerging
      as novel regulators in esophageal adenocarcinoma. Their role has been established
      in various aspects of esophageal adenocarcinoma including carcinogenesis,
      progression, treatment, and prognosis. Therefore, miRNA detection, profiling, and
      quantification have become extremely important for scientists and clinicians. As
      miRNAs are small, their detection can be challenging. There have been various
      methods developed to detect and/or quantify miRNAs. This chapter aims to
      introduce the fundamentals and methods of the most commonly used approaches
      including miRNA microarrays and quantitative real-time polymerase chain reaction
      (RT-qPCR) to detect and quantify miRNAs in esophageal adenocarcinoma.

PMID- 29600377
TI  - RNA Interference-Mediated Gene Silencing in Esophageal Adenocarcinoma.
AB  - RNA interference (RNAi) is a normal physiological mechanism in which a short
      effector antisense RNA molecule regulates target gene expression. It is a
      powerful tool to silence a particular gene of interest in a sequence-specific
      manner and can be used to target against various molecular pathways in esophageal
      adenocarcinoma by designing RNAi targeting key pathogenic genes. RNAi-based
      therapeutics against esophageal adenocarcinoma can be developed using different
      strategies including inhibition of overexpressed oncogenes, blocking cell
      division by interfering cyclins and related genes or enhancing apoptosis by
      suppressing anti-apoptotic genes. In addition, RNAi against multidrug resistance
      genes or chemo-resistance targets may provide promising cancer therapeutic
      options. Here, we describe RNAi technology using MET, a proto-oncogene in
      esophageal adenocarcinoma cells, as a model target. Lentiviral particles
      expressing MET shRNA was used to silence MET genes. Then, Western blot analysis
      was performed to confirm MET knockdown.

PMID- 29600378
TI  - Proteomic Protocol in Esophageal Adenocarcinoma.
AB  - The technique of surface-enhanced laser desorption/ionization time-of-flight
      SELDI-TOF mass spectrometry could be used to establish serum or plasma proteomic
      profiles in esophageal adenocarcinoma. The protein profiles in patients may be
      used to predict survival and monitor response to chemotherapy in patients with
      esophageal adenocarcinoma. Here, a protocol for sample preparation from
      esophageal adenocarcinoma, analysis of proteomic profiles, and collection of
      protein fractions for identification of significant peaks is presented.

PMID- 29600379
TI  - A new approach to the renewable energy-growth nexus: evidence from the USA.
AB  - The climate change is one of the leading problems in the today's world. The rise
      of the renewable energy meets the sustainable growth objectives since it can
      decelerate the climate change. For this purpose, this paper investigates the
      relationship between the renewable energy consumption and the economic growth in
      the United States (USA). Theoretically, the paper constructs the growth model
      that captures the effects of the economic complexity indicator as a measure of
      capabilities and productivity for exporting the "complex" (high value-added)
      products. Empirically, the paper uses the Autoregressive Distributed Lag (ARDL)
      estimations and observes that both the economic complexity and the renewable
      energy consumption lead to a higher rate of economic growth in the USA for the
      period from 1965 to 2016. The paper also discusses the potential policy
      implications of the results for achieving the sustainable growth objectives.

PMID- 29600380
TI  - Increasing water productivity, nitrogen economy, and grain yield of rice by water
      saving irrigation and fertilizer-N management.
AB  - The looming water resources worldwide necessitate the development of water-saving
      technologies in rice production. An open greenhouse experiment was conducted on
      rice during the summer season of 2016 at Huazhong Agricultural University, Wuhan,
      China, in order to study the influence of irrigation methods and nitrogen (N)
      inputs on water productivity, N economy, and grain yield of rice. Two irrigation
      methods, viz. conventional irrigation (CI) and "thin-shallow-moist-dry"
      irrigation (TSMDI), and three levels of nitrogen, viz. 0 kg N ha-1 (N0), 90 kg N
      ha-1 (N1), and 180 kg N ha-1 (N2), were examined with three replications. Study
      data indicated that no significant water by nitrogen interaction on grain yield,
      biomass, water productivity, N uptake, NUE, and fertilizer N balance was
      observed. Results revealed that TSMDI method showed significantly higher water
      productivity and irrigation water applications were reduced by 17.49% in TSMDI
      compared to CI. Thus, TSMDI enhanced root growth and offered significantly
      greater water saving along with getting more grain yield compared to CI. Nitrogen
      tracer (15N) technique accurately assessed the absorption and distribution of
      added N in the soil crop environment and divulge higher nitrogen use efficiency
      (NUE) influenced by TSMDI. At the same N inputs, the TSMDI was the optimal method
      to minimize nitrogen leaching loss by decreasing water leakage about 18.63%,
      which are beneficial for the ecological environment.

PMID- 29600381
TI  - Spectral fitting approach for the determination of enrichment and contamination
      factors in mining sediments using laser-induced breakdown spectroscopy.
AB  - Monitoring of pollution index values in sediments is crucial in assessing the
      environmental impacts of toxic metals in a given location. These indices are
      typically acquired using elaborate and tedious calibration curve-dependent
      techniques such as (inductively coupled plasma - optical emission spectroscopy)
      ICP-OES and (atomic absorption spectroscopy) AAS. In this study, laser-induced
      breakdown spectroscopy (LIBS) was used as a simple and fast alternative method
      for estimating enrichment factor (EF) and contamination factor (CF) of the
      sediment samples obtained from selected mining sites. Quantitative analyses of
      three metal targets (Cd, Pb, and Zn) were done using a calibration-free LIBS
      method based on the Boltzmann population distribution. Both the EF and CF values
      calculated from classical ICP-OES method provided significantly high
      correspondence with the respective EF (R2 = 0.8862-0.9770, p < 0.01-0.05) and CF
      (R2 = 0.9454-0.9714, p < 0.01) obtained from the developed LIBS method. The
      intensity-based LIBS approach identified samples AC2 and CCC as the ones with the
      highest and lowest pollution index values, respectively. The same observation was
      seen using the concentration-based ICP-OES technique which showed good
      correlation between the two methods. The correlation results showed the potential
      of the curve-fitting LIBS analysis in evaluating the level of metal contamination
      in an area without the preparation of matrix-matched calibration curves.

PMID- 29600382
TI  - Optimization of photo-Fenton process for the treatment of prednisolone.
AB  - Prednisolone is a widely prescribed synthetic glucocorticoid and stated to be
      toxic to a number of non-target aquatic organisms. Its extensive consumption
      generates environmental concern due to its detection in wastewater samples at
      concentrations ranged from ng/L to MUg/L that requests the application of
      suitable degradation processes. Regarding the actual treatment options, advanced
      oxidation processes (AOPs) are presented as a viable alternative. In this work,
      the comparison in terms of pollutant removal and energetic efficiencies, between
      different AOPs such as Fenton (F), photo-Fenton (UV/F), photolysis (UV), and
      hydrogen peroxide/photolysis (UV/H2O2), was carried out. Light diode emission
      (LED) was the selected source to provide the UV radiation. The UV/F process
      revealed the best performance, reaching high levels of both degradation and
      mineralization with low energy consumption. Its optimization was conducted and
      the operational parameters were iron and H2O2 concentrations and the working
      volume. Using the response surface methodology with the Box-Behnken design, the
      effect of independent variables and their interactions on the process response
      were effectively evaluated. Different responses were analyzed taking into account
      the prednisolone removal (TOC and drug abatements) and the energy consumptions
      associated. The obtained model showed an improvement of the UV/F process when
      treating smaller volumes and when adding high concentrations of H2O2 and Fe2+.
      The validation of this model was successfully carried out, having only 5% of
      discrepancy between the model and the experimental results. Finally, the
      performance of the process when having a real wastewater matrix was also tested,
      achieving complete mineralization and detoxification after 8 h. In addition,
      prednisolone degradation products were identified. Finally, the obtained low
      energy permitted to confirm the viability of the process.

PMID- 29600383
TI  - Particulate matter on two Prunus spp. decreases survival and performance of the
      folivorous beetle Gonioctena quinquepunctata.
AB  - Woody plants growing along streets and construction sites play an important role
      in removing harmful particulate matter (PM). Researchers rarely consider the
      impact of different types and size fractions of PM deposited on the leaves on
      insect folivores. We determined differences in the accumulation of cement and
      roadside PM on the leaves of two Prunus species (P. padus and P. serotina) with
      different leaf surface structures. We also determined the effect of PM on the
      beetle Gonioctena quinquepunctata, the main pest of these plants. Saplings were
      artificially dusted in greenhouses and leaves were utilised for larval and adult
      insect stages feeding in laboratory conditions. Road PM accumulated in greater
      amounts than did cement PM, regardless of plant species. For both PM sources, P.
      padus accumulated twofold more than did P. serotina. Insect survival was
      negatively affected by PM pollution; however, neither Prunus species nor PM
      source variant significantly affected masses of larvae and pupae, duration of
      larval and pupal development or relative growth rates. The experiment showed
      strong negative influences of PM were noted only for adult insects, due to the
      grazing period being longer than that in larvae. The mass of adult insects and
      the efficiency of conversion of ingested food (ECI) were lower for insects
      exposed to PM than those for control insects. Insects compensated for lower ECI
      by eating a greater total amount of food (TFE). Adult insects gained
      significantly higher mass when fed with P. serotina than with P. padus. The
      effect of PM on analysed plant metabolites was insignificant. Only Prunus sp. and
      date of collection affected the level of condensed tannins and total phenols. Our
      results indicate that, when investigating the effect of the host plant on
      folivore performance, the accumulation of PM, as well as its type and quantity,
      should be taken into account.

PMID- 29600384
TI  - Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated
      Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE
      Single Technology Appraisal.
AB  - As part of the single technology appraisal (STA) process, the National Institute
      for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and
      cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab
      Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated
      metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance
      (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated
      metastatic pancreatic cancer. The review was prompted by a proposed Patient
      Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might
      lead to a change in the guidance. The Liverpool Reviews and Implementation Group
      at the University of Liverpool was the Evidence Review Group (ERG). This article
      summarises the ERG's review of the company's evidence submission for Nab-Pac +
      Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE
      listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in
      combination with capecitabine (Gem + Cap), and a combination of oxaliplatin,
      irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the
      comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized
      controlled trial. Analysis of progression-free survival (PFS) and overall
      survival (OS) showed statistically significant improvement for patients treated
      with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac +
      Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta
      analysis (NMA). Results of the NMA did not indicate a statistically significant
      difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem +
      Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness
      evidence were difficulties in identifying the patient population for whom
      treatment with Nab-Pac + Gem is most appropriate, and violation of the
      proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted
      methodological issues in the cost-effectiveness analysis pertaining to the
      modelling of survival outcomes, estimation of drug costs and double counting of
      adverse-event disutilities. The AC accepted all the ERG's amendments to the
      company's cost-effectiveness model; however, these did not make important
      differences to the incremental cost-effectiveness ratios (ICERs). The company's
      base-case ICER was L46,932 per quality-adjusted life-year (QALY) gained for the
      comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was
      dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's
      base case. The AC concluded that the most plausible ICER for treatment with Nab
      Pac + Gem versus Gem was in the range of L41,000-L46,000 per QALY gained. The AC
      concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or
      FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life
      criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life
      criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that
      although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem +
      Cap were difficult to distinguish, they were identifiable in clinical practice.
      The AC recommended treatment with Nab-Pac + Gem for patients with untreated
      metastatic pancreatic cancer for whom other combination chemotherapies were
      unsuitable and who would otherwise receive Gem.

PMID- 29600385
TI  - Long-term results of a modified Spitzy shelf operation for developmental
      dysplasia of the hip in adults and adolescents.
AB  - The purpose of the current study was to retrospectively evaluate the long-term
      outcome of our shelf operation for acetabular dysplasia in adults and
      adolescents. We evaluated the outcome of shelf operation performed in 35 hips of
      32 patients with acetabular dysplasia between 1978 and 1996. The mean age at the
      time of surgery was 30.6 years, and the mean follow-up period was 25.9 years. The
      pre-operative stage of osteoarthritis was Tonnis grade 0 in 12 hips and grade 1
      in 23 hips. Clinical evaluation using the JOA hip score showed more than 85 of
      100 points over 25 years. Radiologically, acetabular index was significantly
      improved after operation. Osteoarthritis deteriorated to grade 3 in 8 of 35 hips
      (23%) at an average 17.1 years, and accordingly 3 of those 8 hips were converted
      to THA. The shelf height was significantly higher in those which advanced to
      grade 3 than in those which did not. There were no significant differences in
      mean sharp angle, CE angle, AHI, and roundness index. Mean survival was 74% with
      grade 3 as the endpoint and 72% with THA conversion as the endpoint. Shelf
      operation provides satisfactory long-term outcome in adults and adolescents with
      acetabular dysplasia. Higher location of the shelf is a risk factor for
      advancement of osteoarthritis, whereas sphericity of the femoral head does not
      affect the long-term results. Further studies are needed to clarify the risk
      factors about OA progression among the patients with acetabular dysplasia, like
      as the assessment of three-dimensional morphology of hip joints.

PMID- 29600386
TI  - Survival impact of post-progression chemotherapy in advanced gastric cancer:
      systematic review and meta-analysis.
AB  - PURPOSE: We conducted a systematic review and meta-analysis on survival impact of
      post-progression chemotherapy (post-Cx) after first-line chemotherapy (1st-Cx)
      and after second-line chemotherapy (2nd-Cx), and survival benefit of third-line
      chemotherapy (3rd-Cx) for advanced gastric cancer (AGC). METHODS: Phase III
      trials of systemic chemotherapy for AGC published in English between 2005 and
      2015 or presented at annual meetings of ASCO or ESMO between 2013 and 2015 were
      searched. Numbers of patients, types of chemotherapy, patient baseline,
      proportion of patients receiving post-Cx (post-Cx%), median progression-free
      survival (mPFS), and median overall survival (mOS) of each treatment arm were
      surveyed; trials not reporting these parameters were excluded. Median post
      progression survival (mPPS) was calculated as the difference between mOS and
      mPFS. Weighted Spearman's correlation coefficients between post-Cx% and survival
      outcomes (mOS and mPPS) were calculated. The effect of post-Cx% on survival
      outcomes adjusted for the types of chemotherapy and patient characteristics was
      evaluated by meta-regression. RESULTS: Overall, 25 phase III trials of AGC were
      selected: 15 trials with 31 arms for 1st-Cx, and 10 trials with 16 arms for 2nd
      Cx. Weighted Spearman's correlation coefficients for post-Cx% and mOS/mPPS were
      0.520/0.739 for 1st-Cx, and 0.767/0.823 for 2nd-Cx. Meta-regression analyses
      adjusting for types of chemotherapy, age, and PS showed that a 10% increase in
      post-Cx% was associated with prolongation of mOS by 1.033 months for 1st-Cx and
      0.344 months for 2nd-Cx. CONCLUSIONS: Post-Cx% both after 1st-Cx and 2nd-Cx were
      correlated with mOS/mPPS, suggesting a survival benefit of 3rd-Cx in addition to
      that of 2nd-Cx for AGC.

PMID- 29600387
TI  - The responses of cucumber plants subjected to different salinity or fertilizer
      concentrations and reproductive success of Tetranychus urticae mites on these
      plants.
AB  - The plant stress hypothesis posits that a herbivore's reproductive success
      increases when it feeds on stressed plants, while the plant vigor hypothesis
      predicts that a herbivore preferentially feeds on more vigorous plants. We
      examined these opposing hypotheses by growing spider mites (Tetranychus urticae)
      on the leaves of stressed and healthy (vigorous) cucumber plants. Host plants
      were grown under controlled conditions at low, moderate, and high concentrations
      of NaCl (to induce salinity stress), at low, moderate, and high fertilizer
      concentrations (to support growth), and without these additions (control). The
      effects of these treatments were evaluated by measuring fresh and dry plant
      biomass, carotenoid and chlorophyll content, antioxidant enzyme activity, and
      concentrations of PO43-, K+, and Na+ in plant tissues. The addition of low
      concentrations of fertilizer increased dry mass, protein, and carotenoid content
      relative to controls, suggesting a beneficial effect on plants. The highest NaCl
      treatment (2560 mg L-1) resulted in increased Na+ and protein content relative to
      control plants, as well as reduced PO43-, K+, and chlorophyll levels and reduced
      catalase and ascorbate peroxidase enzyme activity levels. Analysis of life table
      data of T. urticae mites raised on leaves from the aforementioned plant groups
      showed the intrinsic rate of increase (r) for mites was 0.167 day-1 in control
      specimens, 0.125 day-1 for mites reared on plants treated with a moderate
      concentration of fertilizer (10 mL L-1), and was highest (0.241 day-1) on plants
      grown under moderate salinity conditions (1920 mg L-1 NaCl). Reproductive success
      of T. urticae did not differ on plants watered with a moderate concentration of
      NaCl or a high concentration of fertilizer. The moderately-stressed plants formed
      a favorable environment for the development and reproduction of spider mites,
      supporting the plant stress hypothesis.

PMID- 29600388
TI  - Alpha-synuclein is present in dental calculus but not altered in Parkinson's
      disease patients in comparison to controls.
AB  - INTRODUCTION: In autopsy cases staged for sporadic Parkinson's disease (PD), the
      neuropathology is characterized by a preclinical phase that targets the enteric
      nervous system of the gastrointestinal tract (GIT). Therefore, the ENS might be a
      source of potential (presymptomatic) PD biomarkers. METHODS: In this clinically
      based study, we examined the alpha-synuclein (alphaSyn) concentration in an
      easily accessible protein storage medium of the GIT, dental calculus, in 21/50
      patients with PD and 28/50 age- and gender-matched controls using ELISA. RESULTS:
      alphaSyn was detectable in dental calculus and the median concentration in the
      control patients was 8.6 pg/mg calculus (interquartile range 2.6-13.1 pg/mg).
      alphaSyn concentrations were significantly influenced by blood contamination and
      samples with a hemoglobin concentration of > 4000 ng/mL were excluded. There was
      no significant difference of alphaSyn concentrations in the dental calculus of PD
      patients (5.76 pg/mg, interquartile range 2.91-9.74 pg/mg) compared to those in
      controls (p = 0.40). CONCLUSION: The total alphaSyn concentration in dental
      calculus is not a suitable biomarker for sporadic PD. Disease-related variants
      such as oligomeric or phosphorylated alphaSyn in calculus might prove to be more
      specific.

PMID- 29600389
TI  - A novel frameshift variant in the CADASIL gene NOTCH3: pathogenic or not?
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) represents the most common monogenic cause of adult
      onset ischemic stroke and vascular dementia. It is caused by heterozygous
      missense mutations in the NOTCH3 gene, encoding a transmembrane receptor protein
      on vascular smooth muscle cells. Classical CADASIL mutations affect conserved
      cysteine residues of the Notch3 protein. By contrast, the role of non-canonical
      genetic variation in NOTCH3, in particular of variants causing a hypomorphic
      Notch3 protein, is subject to an ongoing scientific debate. In this context, we
      here report a novel NOTCH3 frameshift variant in exon 18 (NM_000435.2:
      c.2853_2857delTCCCG), causing a frameshift and introducing a premature stop
      codon, which was detected in a 43-year-old woman and her father. Both carriers of
      the variant were carefully evaluated, including serial follow-up in the index.
      Neither clinical nor imaging features provided convincing evidence for a
      classical CADASIL phenotype, thus reinforcing the concept of hypomorphic NOTCH3
      variants most likely not being causative for CADASIL. Our finding, which is
      discussed in the light of the published literature, has practical implications
      for interpreting results of NOTCH3 molecular genetic testing as well as patient
      counseling.

PMID- 29600391
TI  - Safety and Antioxidant Efficacy Profiles of Rutin-Loaded Ethosomes for Topical
      Application.
AB  - Topical application of dermocosmetics containing antioxidant and/or the intake of
      antioxidants through diet or supplementation are remarkable tools in an attempt
      to slow down some of the harmful effects of free radicals. Rutin is a strong
      antioxidant compound used in food and pharmaceutical industries. It was
      established that rutin presents a low skin permeation rate, a property that could
      be considered an inconvenience to the satisfactory action for a dermocosmetic
      formulation to perform its antioxidant activity onto the skin. Therefore, it is
      indispensable to improve its delivery, aiming at increasing its antioxidant
      capacity in deeper layers of the epidermis, being a possibility to associate the
      rutin to liposomal vesicles, such as ethosomes. Thus, in this work, the pre
      clinical safety of rutin-loaded ethosomes was investigated employing an in vitro
      method, and the clinical safety and efficacy were also assessed. Rutin-loaded
      ethosomes were efficaciously obtained in a nanoscale dimension with a relevant
      bioactive compound loading (80.2%) and provided antioxidant in vitro activity in
      comparison with the blank sample. Pre-clinical and clinical safety assays assured
      the innocuous profile of the rutin-loaded ethosomes. The ethosomes containing the
      bioactive compound accomplished a more functional delivery system profile, since
      in the tape stripping assay, the deeper layers presented higher rutin amounts
      than the active delivered in its free state. However, the ex vivo antioxidant
      efficacy test detected no positive antioxidant activity from the rutin-loaded
      ethosomes, even though the in vitro assay demonstrated an affirmative antioxidant
      action.

PMID- 29600392
TI  - [Augmented reality-technological progress in imaging procedures].

PMID- 29600390
TI  - Supervised versus unsupervised technology-based levodopa monitoring in
      Parkinson's disease: an intrasubject comparison.
AB  - We aimed to assess the intrasubject reproducibility of a technology-based
      levodopa (LD) therapeutic monitoring protocol administered in supervised versus
      unsupervised conditions in patients with Parkinson's disease (PD). The study
      design was pilot, intrasubject, single center, open and prospective. Twenty
      patients were recruited. Patients performed a standardized monitoring protocol
      instrumented by an ad hoc embedded platform after their usual first morning LD
      dose in two different randomized ambulatory sessions: one under a physician's
      supervision, the other self-administered. The protocol is made up of serial motor
      and non-motor tests, including alternate finger tapping, Timed Up and Go test,
      and measurement of blood pressure. Primary motor outcomes included comparisons of
      intrasubject LD subacute motor response patterns over the 3-h test in the two
      experimental conditions. Secondary outcomes were the number of intrasession
      serial test repetitions due to technical or handling errors and patients'
      satisfaction with the unsupervised LD monitoring protocol. Intrasubject LD motor
      response patterns were concordant between the two study sessions in all patients
      but one. Platform handling problems averaged 4% of total planned serial tests for
      both sessions. Ninety-five percent of patients were satisfied with the self
      administered LD monitoring protocol. To our knowledge, this study is the first to
      explore the potential of unsupervised technology-based objective motor and non
      motor tasks to monitor subacute LD dosing effects in PD patients. The results are
      promising for future telemedicine applications.

PMID- 29600393
TI  - Chlorhexidine use in adult patients on ICU.

PMID- 29600394
TI  - Correction to: Efficacy and Safety of Switching to Ixekizumab in Etanercept Non
      Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in
      Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).
AB  - The article Efficacy and Safety of Switching to Ixekizumab in Etanercept Non
      Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in
      Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3) written by Andrew
      Blauvelt.

PMID- 29600395
TI  - Deep brain stimulation of the thalamic ventral intermediate nucleus for
      Benedikt's syndrome mainly present as tremor: a long-term case observation.
AB  - Benedikt's syndrome (BS) is caused by the lesion in the midbrain and specifically
      manifests a series of symptoms, including ipsilateral third nerve palsy,
      contralateral tremor, hemiataxia, and hyperactive tendon reflexes. Deep brain
      stimulation (DBS) for BS emerges as a new approach and achieves successfully
      results. We report a successful case report of thalamic ventral intermediate
      (VIM) nucleus DBS for a patient with BS. During follow-up of 3 years, DBS
      successfully control the tremor and greatly improve his living and working
      quality. We consider that VIM DBS may have sustained benefit for refractory BS
      that mainly presents as tremor.

PMID- 29600396
TI  - "You Worry, 'cause You Want to Give a Reasonable Account of Yourself": Gender,
      Identity Management, and the Discursive Positioning of "Risk" in Men's and
      Women's Talk About Heterosexual Casual Sex.
AB  - Heterosexual casual sex is routinely depicted as a physically, socially, and
      psychologically "risky" practice. This is the case in media accounts,
      psychological research, and other academic work. In this article, we examine 15
      men's and 15 women's talk about casual sex from a discursive psychological stance
      to achieve two objectives. Firstly, we confirm the categories of risk typically
      associated with casual sex but expand these to include a domain of risks related
      to (gendered) identities and representation. Men's talk of risk centered on
      concerns about sexual performance, whereas women's talk centered on keeping safe
      from violence and sexual coercion. The notion of a sexual reputation was also
      identified as a risk and again manifested differently for men and women. While
      women were concerned about being deemed promiscuous, men displayed concern about
      the quality of their sexual performance. Secondly, within this talk about risks
      of casual sex, the participants' identities were identified as "at risk" and
      requiring careful management within the interview context. This was demonstrated
      by instances of: keeping masculinity intact in accounts of no erection,
      negotiating a responsible subject position, and crafting agency in accounts of
      sexual coercion-in the participants' talk. We argue that casual sex, as situated
      within dominant discourses of gendered heterosexuality, is a fraught practice for
      both men and women and subject to the demands of identity representation within
      co-present interactions.

PMID- 29600397
TI  - Sex/Gender/Sexual Science Research 24/7.

PMID- 29600398
TI  - Mutations in LRRK2 amplify cell-to-cell protein aggregate propagation: a
      hypothesis.

PMID- 29600399
TI  - Bladder wall injection of mesenchymal stem cells ameliorates bladder
      inflammation, overactivity and nociception in a chemically induced interstitial
      cystitis-like rat model.

PMID- 29600400
TI  - Do patient characteristics predict which patients with overactive bladder benefit
      from a higher fesoterodine dose?
AB  - INTRODUCTION AND HYPOTHESIS: We sought to determine whether baseline
      characteristics predict which overactive bladder (OAB) patients benefit from
      fesoterodine 8 mg versus 4 mg. METHODS: In double-blind, placebo-controlled,
      flexible-dose trials, baseline characteristics of OAB patients with >= 1 urgency
      urinary incontinence (UUI) episodes/24 h who escalated from fesoterodine 4 mg to
      8 mg were evaluated. Possible dose-escalation predictors (age; sex; previous
      antimuscarinic use; UUI, micturitions, and urgency episodes/24 h; race; body mass
      index; time to dose escalation; OAB duration) were compared in escalators versus
      non-escalators. Patients from fixed-dose trials with dose-escalator
      characteristics were identified (matched dose-escalator sample) to assess changes
      from baseline with fesoterodine 4 mg, 8 mg, and placebo. RESULTS: In flexible
      dose trials, significant predictors of fesoterodine dose escalation were younger
      age (<= 65.8 years), greater number of baseline micturitions (>= 13.1) and
      urgency episodes/24 h (>= 10.9), greater OAB duration (>= 9.1 years), and more
      frequent previous antimuscarinic use (58.3%), but not baseline UUI episodes/24 h.
      In the matched dose-escalator sample (fesoterodine 4 mg: n = 215; 8 mg: n = 198;
      placebo: n = 217), change from baseline in UUI episodes significantly improved
      with fesoterodine 8 mg versus 4 mg (P = 0.043) and with both doses versus placebo
      (P < 0.001). Dry mouth and constipation rates were higher with fesoterodine 8 mg.
      CONCLUSIONS: Dose-escalator patients had a significantly greater UUI response
      with fesoterodine 8 mg versus 4 mg. Given the potential for adverse events,
      fesoterodine 4 mg is recommended to start; however, patients with UUI and
      identified predictors may benefit from initial treatment with fesoterodine 8 mg
      or rapid dose escalation.

PMID- 29600401
TI  - Early catheter removal after pelvic floor reconstructive surgery: a randomized
      trial.
AB  - INTRODUCTION AND HYPOTHESIS: Studies have yet to examine the impact of day-of
      surgery voiding trials on post-operative urinary retention in women undergoing
      obliterative and apical suspension procedures for pelvic organ prolapse. Our
      objective was to evaluate if time to spontaneous void after these procedures is
      shorter when a voiding trial is performed on the day of surgery compared with our
      standard practice of post-operative day 1. METHODS: We conducted a randomized,
      parallel-arm trial in patients undergoing major pelvic floor reconstructive
      surgery. Women were randomized 1:1 to an early (4 h post-operatively on the day
      of surgery) or a standard (6 am on post-operative day 1) retrograde voiding
      trial. RESULTS: A total of 57 women consented. Mean age and BMI were 65 +/- 11
      and 27.9 +/- 4.4. Most women had stage III pelvic organ prolapse (77.2%). Groups
      had similar baseline characteristics. In the intention-to-treat analysis (n =
      57), there was no difference in time to spontaneous void in the early versus
      standard voiding trial groups (15.9 +/- 3.8 vs 28.4 +/- 3.1 hours, p = 0.081). In
      the adjusted analysis using mutlivariable linear regression, an early voiding
      trial decreased the time to spontaneous void (abeta -2.00 h, p = 0.031) when
      controlling for vaginal packing and stage IV prolapse. In the per-protocol
      analysis, which excluded 4 patients for crossover, spontaneous void occurred 17
      hours faster in the early voiding trial group (14.6 +/- 3.7 vs 31.8 +/- 2.9
      hours; p = 0.022). Early voiding trial patients experienced ambulation sooner and
      more often than the standard group (p = 0.02). CONCLUSIONS: A day-of-surgery
      voiding trial did not prolong catheter use after obliterative and apical
      suspension procedures.

PMID- 29600402
TI  - Bladder management during pregnancy in women with spinal-cord injury: an
      observational, multicenter study.
AB  - INTRODUCTION AND HYPOTHESIS: Pregnancy in women with spinal-cord injury (SCI)
      poses a clinical challenge. We hypothesized that changes in the management of
      neurogenic bladder during pregnancy are commonly required and should receive more
      attention. METHODS: Data were collected by retrospective analysis of medical
      records and via cross-sectional survey of 52 women with SCI, representing 67
      pregnancies, at ten Italian neurourological clinics. All participants provided
      informed consent. RESULTS: Between 1976 and 2013, 39 participants had one child,
      11 had two children, and two had three children. Mean age at the time of SCI was
      18 years and at the time of first pregnancy was 30 years. Delivery occurred from
      weeks 32 to 40 in 98% of first and second pregnancies, and 94% of neonates were
      healthy. Oxybutynin was used by four women during five pregnancies, which
      resulted in delivery of healthy babies. Intermittent catheterization was used
      before 54% of first pregnancies and 39% of second pregnancies. Bladder management
      was altered during 45% of these pregnancies, and the most common changes were
      increased use or frequency of intermittent catheterization or use of an
      indwelling catheter. Urinary tract infections occurred in 48% of pregnancies, and
      an irregular course was reported in 13% of pregnancies mainly related to
      tetraplegia and urological complications. CONCLUSIONS: Pregnancy in women with
      SCI generally has good outcomes and limited risks but frequently necessitates
      changes in the management of neurogenic bladder. High levels of awareness and
      focused monitoring of bladder issues are recommended.

PMID- 29600403
TI  - Effect of subsequent vaginal delivery on bowel symptoms and anorectal function in
      women who sustained a previous obstetric anal sphincter injury.
AB  - INTRODUCTION AND HYPOTHESIS: Our primary objective was to prospectively evaluate
      anorectal symptoms, anal manometry and endoanal ultrasound (EAUS) in women who
      followed the recommended mode of subsequent delivery following index obstetric
      anal sphincter injuries (OASIs) using our unit's standardised protocol. Our
      secondary objectives were to evaluate the role of internal anal sphincter defects
      and also to compare outcomes in a subgroup of symptomatic women with normal
      anorectal physiology. METHODS: This is a prospective follow-up study of pregnant
      women with previous OASIs who were counselled regarding subsequent mode of
      delivery between January 2003 and December 2014. Assessment involved the St
      Mark's Incontinence Score (SMIS), anal manometry and EAUS at both antepartum and
      3-month postpartum visits. Data were analysed using Wilcoxon and Mann-Whitney U
      tests. RESULTS: Three hundred and fifty women attended the perineal clinic over
      the study period, of whom 122 met the inclusion criteria (99 vaginal delivery
      [VD], 23 caesarean section). No significant worsening of anorectal symptoms was
      observed following subsequent delivery in the VD group (p = 0.896), although a
      reduced squeeze pressure was observed at 3 months postpartum (p < 0.001). There
      were no new defects on EAUS in either group. CONCLUSIONS: This study showed no
      significant worsening of bowel symptoms and sphincter integrity apart from lower
      squeeze pressures at 3 months postpartum in the VD group when our standardised
      protocol was used to recommend subsequent mode of delivery. In the absence of a
      randomised study, use of this protocol can aid clinicians in their decision
      making.

PMID- 29600404
TI  - Differential gene expression of extracellular-matrix-related proteins in the
      vaginal apical compartment of women with pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a multifactorial
      disorder that impairs the quality of life (QoL) of older women in particular. The
      purpose of this study was to elucidate the pathogenesis of POP by focusing on the
      extracellular matrix (ECM). METHODS: Patients were classified into two groups
      with or without cervical elongation-using the POP quantification system.
      Specimens were obtained from 29 women with POP during hysterectomy. The
      expression of fibulin-5, elastin, integrin beta1 (ITGbeta1), lysyl oxidase-like
      protein-1 (LOXL1) and collagen in the vagina, uterosacral ligament, and uterine
      cervix was investigated by quantitative real-time polymerase chain reaction (RT
      PCR) and correlation between gene levels and severity of POP examined. The
      location of proteins was analyzed using immunohistochemical staining and
      expression of fibulin-5 protein analyzed by Western blotting. RESULTS: Fibulin-5
      and elastin were mainly expressed in lamina propria and fibromuscular layers of
      the vagina and uterosacral ligament. Gene levels of fibulin-5 and ITGbeta1 in
      uterosacral ligaments increased with severity of POP in women with cervical
      elongation, while no correlation was observed in women with a normal cervix. In
      women with uterine cervical elongation, each ECM-related gene significantly
      increased with POP staging. Furthermore, fibulin-5 protein also increased in the
      uterosacral ligament and uterine cervix. CONCLUSIONS: The severity of POP and
      gene expression of ECM-related proteins were inversely correlated in vaginal
      tissue in a normal and elongated cervix. These results suggested that the
      differing progression of the two types of POP have a relationship with ECM
      related protein.

PMID- 29600405
TI  - Comparing postoperative voiding dysfunction after mid-urethral sling using either
      a Babcock or Kelly clamp tensioning technique.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to compare postoperative urinary
      retention using the Babcock and Kelly clamps for retropubic midurethral sling
      (RPS) tensioning. METHODS: This was a retrospective cohort of isolated RPS
      procedures from December 2010 through April 2016 by five fellowship-trained
      surgeons at two institutions. Slings were tensioned with a Babcock clamp by
      grasping a 3-mm midline fold of mesh (RPS-B) or a Kelly clamp as a spacer between
      the sling and suburethral tissue (RPS-K). Assessment of urinary retention
      included the primary outcome of postoperative catheterization and several
      secondary outcomes, including discharge home with a catheter, within 1 year of
      surgery. Analysis of covariance was used to compute the mean difference in
      duration of catheterization and log-binomial regression was used to calculate
      risk ratios (RR) and 95% confidence intervals (CI). RESULTS: We included 240
      patients. The RPS-B group had a lower body mass index and was more likely to be
      menopausal, have had pelvic organ prolapse surgery, and have a lower maximum
      urethral closure pressure than the RPS-K group. The mean duration of
      catheterization was similar, as demonstrated by the crude (0.21 days [-0.30
      0.71]) and BMI-adjusted (0.07 days [-0.41-0.55]) mean difference in duration of
      catheterization. The incidence of postoperative OAB symptoms was comparable
      between the groups (BMI-adjusted RR: 0.95 (0.80-1.1)), and the incidence of
      revision did not differ (p = 0.7). CONCLUSIONS: The Babcock and Kelly clamp
      tensioning techniques appear comparable, with a low incidence of prolonged
      postoperative catheterization. Most catheters were removed on the day of the
      surgery. It is reasonable to tension retropubic midurethral slings with either
      method.

PMID- 29600406
TI  - [Selective mutism].
AB  - Selective mutism was first described in the medical literature 140 years ago. The
      diagnosis came into the focus of adult psychiatry with the appearance of DSM-5.
      Henceforth, selective mutism during infancy, adolescence and also adulthood is
      specified as an independent anxiety disorder. It often begins in early childhood
      with a kind of speechlessness in certain situations. A diagnostic clarification
      often only takes place after school enrolment. Very often comorbid anxiety
      disorders, especially social phobia and depression also occur. The course is very
      variable and with some affected persons regression of the pathology occurs
      suddenly and completely and with others there is a slow regression of the
      symptoms. Equally the disorder can persist until adulthood. Whilst formerly a
      traumatic genesis was assumed, a multifactorial etiology with genetic,
      psychological and language-associated effects is nowadays presumed. The therapy
      is supported through psychotherapy, speech therapy and psychopharmacology.

PMID- 29600407
TI  - What is this image? 2018: image 6 result : Cardiac FDG uptake predominantly
      affecting the atria.

PMID- 29600408
TI  - Independent regulation of renin-angiotensin-aldosterone system in the kidney.
AB  - Renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating
      renal hemodynamics and functions, as well as in the pathophysiology of
      hypertension and renal disease. In the kidney, angiotensin II (Ang II) production
      is controlled by independent multiple mechanisms. Ang II is compartmentalized in
      the renal interstitial fluid with much higher concentrations than those existing
      in the circulation. Inappropriate activation of the intrarenal RAAS is an
      important contributor to the pathogenesis of hypertension and renal injury. It
      has been revealed that intrarenal Ang II levels are predominantly regulated by
      angiotensinogen and therefore, urinary angiotensinogen could be a biomarker for
      intrarenal Ang II generation. In addition, recent studies have demonstrated that
      aldosterone contributes to the progression of renal injury via direct actions on
      glomerular podocytes, mesangial cells, proximal tubular cells and tubulo
      interstitial fibroblasts through the activation of locally expressed
      mineralocorticoid receptor. Thus, it now appears that intrarenal RAAS is
      independently regulated and its inappropriate activation contributes to the
      pathogenesis of the development of hypertension and renal disease. This short
      review article will focus on the independent regulation of the intrarenal RAAS
      with an emphasis on the specific role of angiotensinogen.

PMID- 29600409
TI  - Alcohol consumption and incidence of proteinuria: a retrospective cohort study.
AB  - BACKGROUND: Previous studies report conflicting results of a dose-dependent
      association between alcohol consumption and incidence of chronic kidney disease.
      Only a few studies have assessed the clinical impact of > 45-65 g/day of
      critically high alcohol consumption. METHODS: This retrospective cohort study
      included 88,647 males and 88,925 females with dipstick urinary protein <= +/- and
      estimated glomerular filtration rate >= 60 mL/min/1.73 m2 at their first annual
      health examinations between April 2008 and March 2010 in Japan. The exposure was
      the self-reported alcohol consumption. The outcome was proteinuria defined as
      dipstick urinary protein >= 1 + or >= 2 +. RESULTS: During median 1.8 years
      (interquartile range 1.0-2.1) of the observational period, 5416 (6.1%) males and
      3262 (3.7%) females developed proteinuria defined as dipstick urinary protein >=
      1 +. In males, a U-shape association between alcohol consumption and proteinuria
      was observed in a multivariable-adjusted Poisson regression model [incidence rate
      ratio (95% confidence interval) of rare, occasional, and daily drinkers with <=
      19, 20-39, 40-59, and >= 60 g/day: 1.00 (reference), 0.86 (0.79-0.94), 0.70 (0.64
      0.78), 0.82 (0.75-0.90), 1.00 (0.90-1.11), and 1.00 (0.85-1.17), respectively],
      whereas a J-shape association was observed in females [1.00 (reference), 0.81
      (0.75-0.87), 0.74 (0.64-0.85), 0.93 (0.78-1.11), 1.09 (0.83-1.44), and 1.45 (1.02
      2.08), respectively]. Similar associations with dipstick urinary protein >= 2 +
      were shown in males and females. CONCLUSIONS: Moderate alcohol consumption was
      associated with lower risk of proteinuria in both males and females. Females with
      >= 60 g/day of high alcohol consumption were at higher risk of proteinuria,
      whereas males were not. Females were more vulnerable to high alcohol consumption,
      than males.

PMID- 29600410
TI  - Butyrylcholinesterase level as an independent factor of erythropoiesis
      stimulating agent resistance in patients on maintenance hemodialysis: a single
      center cross-sectional study.
AB  - BACKGROUND: Erythropoiesis-stimulating agent (ESA) responsiveness is related to
      the nutritional status of patients on hemodialysis (HD). Serum
      butyrylcholinesterase (BChE), an alpha-glycoprotein, may decrease in case of
      malnutrition. We investigated whether BChE was independently related to ESA
      resistance in patients on HD. METHODS: The laboratory data and ESA resistance
      index (ERI), defined as ESA dosage per week divided by dry weight and hemoglobin,
      were investigated in 215 patients on HD between July and September 2017.
      Malnutrition was defined as Geriatric Nutritional Risk Index (GNRI) of < 91.2.
      The patients were stratified into two groups: ERI-high (ERI >= 9.44) and ERI-low
      (ERI < 9.44) groups. Variables such as patient's background, medication, and
      laboratory data were compared between the two groups. The optimal cutoff value of
      BChE for higher ERI was determined using receiver operating characteristic
      analysis. Factors independently associated with higher ERI were determined using
      multivariate logistic regression analysis. RESULTS: The median and optimal cutoff
      values of ERI and BChE were 6.51 and 200 IU/L, respectively. The study included
      71 (33%) and 144 (67%) patients in the ERI-high and ERI-low groups, respectively.
      Significant between-group differences were observed concerning age, hemoglobin,
      ESA dose, lipid profiles, serum albumin, body mass index, GNRI, iron metabolism
      markers, ferric medicines, and BChE. Multivariate analysis showed that BChE < 200
      IU/L (odds ratio 3.67; 95% confidence interval 1.73-7.77) continued to be an
      independent factor associated with higher ERI after adjusting for potential
      confounders, which was a similar odds ratio as GNRI < 91.2. CONCLUSION: BChE may
      be an independent indicator of ESA resistance.

PMID- 29600411
TI  - Differential Modulation of Endophytic Microbiome of Ginger in the Presence of
      Beneficial Organisms, Pathogens and Both as Identified by DGGE Analysis.
AB  - Endophytic microorganisms play a significant role in plants response to
      beneficial organisms and pathogens. In the current study, endophytic
      microorganisms from Zingiber officinale were screened for in vitro inhibition
      against Pythium myriotylum. From this, Burkholderia vietnamiensis ZoB74 was
      selected as an organism with remarkable antifungal effect. Further, the study
      focussed on analysis of in vivo changes in endophytic bacterial community of Z.
      officinale in presence of selected organisms and the pathogen P. myriotylum by
      PCR-DGGE. 16S rDNA sequencing of bacterial community after DGGE has resulted in
      the identification of a group of uncultured bacteria as the predominant microbial
      community of rhizome under various conditions of treatment. High frequency
      dominance of these endophytic bacteria suggests their role in disease resistance
      to soft rot in ginger. This also revealed the variation of endophytic microbiome
      of Z. officinale under biotic stress. Hence the study provides molecular insight
      into uncultured microbiome and its stress-inducible variation in ginger rhizome.

PMID- 29600412
TI  - Associations of monoamine oxidase A gene first exon methylation with sexual abuse
      and current depression in women.
AB  - Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine
      oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In
      addition, PA and SA may alter gene activity through epigenetic mechanisms such as
      DNA methylation, thereby further modifying risk for disorders. We investigated
      whether methylation in a region spanning the MAOA first exon and part of the
      first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence,
      drug dependence, depression disorders, anxiety disorders, and conduct disorder.
      114 Swedish women completed standardized diagnostic interviews and questionnaires
      to report PA and SA, and provided saliva samples for DNA extraction. DNA was
      genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of
      interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated
      with hypermethylation of the MAOA first exon relative to no-abuse, and the
      association was robust to adjustment for psychoactive medication, alcohol and
      drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not
      their interaction, was associated with MAOA methylation. SA associated with all
      measured mental disorders. Hypermethylation of MAOA first exon mediated the
      association of SA with current depression, and both methylation levels and SA
      independently predicted lifetime depression. Much remains to be learned about the
      independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA
      first exon.

PMID- 29600413
TI  - Palliative sedation in advanced cancer patients hospitalized in a specialized
      palliative care unit.
AB  - PURPOSE: To describe the practice of palliative sedation (PS) in patients with
      advanced cancer in a specialized palliative care (PC) unit in Colombia. METHODS:
      Descriptive prospective study including all adults with cancer hospitalized under
      PS in a cancer institute between January and July 2015 in Colombia. Variables
      examined were diagnosis, physical functioning, symptoms at the start of sedation,
      medications and dosages used, and type, level, and time of sedation. Descriptive
      and correlational statistics were obtained. RESULTS: Sixty-six patients were
      included, 70% of which were women. The patients had an average age of 61 years
      (range 24-87), and 74% had a Karnofsky Index (KI) of 50% or less. The most
      frequent diagnosis was breast cancer (22%), and 82% had metastatic cancer. The
      prevalence of palliative sedation was 2% and the most common symptoms indicating
      it were dyspnea (59%), delirium (45%), and pain (32%). All patients received
      midazolam as a sedative. The average time between the interval start and
      culmination of sedation was 44 h. There was a significant and inverse
      relationship between functionality and time under sedation. CONCLUSIONS:
      Palliative sedation is a valid therapeutic option for refractory symptoms causing
      suffering. The results correspond to international reports and guidelines, which
      suggests that PS is tailored to the needs of the individual patient while
      maintaining a high scientific standard, even in a context where PC is under
      development. However, further development of strategies and clear indications
      towards the use of PS in Colombia are needed, given its still scarce use.

PMID- 29600415
TI  - The cultural expression of spiritual distress in Israel.
AB  - BACKGROUND: Although spiritual distress is present across cultures, the ways in
      which patients experience it vary between cultures. Our goal was to examine the
      cultural expression and key indicators of spiritual distress in Israel. METHODS:
      We conducted a structured interview of 202 oncology outpatients in a cross
      sectional study. Self-diagnosis of spiritual distress, which is a demonstrated
      gold standard for identifying its presence, was compared with the Facit-Sp-12 and
      a number of other items (from the Spiritual Injury Scale and newly developed
      Israeli items) hypothesized as Israeli cultural expressions of spiritual
      distress, demographic and medical data, and patient desire to receive spiritual
      care. RESULTS: Significant variation was found between Israeli cultural
      expression of spiritual distress and that found in studies from other countries.
      Key expressions of spiritual distress in this study included lack of inner peace,
      grief, and an inability to accept what is happening. Items related to faith were
      not significant, and loss of meaning showed mixed results. Patients requesting
      spiritual care were more likely to be in spiritual distress. No demographic or
      medical data correlated with spiritual distress. CONCLUSIONS: Specially designed
      interventions to reduce spiritual distress should address the expressions of the
      distress specific to that culture. Studies of the efficacy of spiritual care can
      examine the extent of spiritual distress in general or of its specific cultural
      expressions.

PMID- 29600416
TI  - Gastric cancer prevention and Helicobacter pylori.

PMID- 29600414
TI  - Metastatic epidural spinal cord compression: does timing of surgery influence the
      chance of neurological recovery? An observational case-control study.
AB  - PURPOSE: Metastatic epidural spinal cord compression (MESCC) is radiologically
      defined as an epidural metastatic lesion causing the displacement of the spinal
      cord from its normal position in the vertebral canal. The purpose of this paper
      is the evaluation of the influence of timing of surgery on the chance of
      neurological recovery. METHODS: This is a retrospective observational case
      control study performed on patients with MESCC from solid tumors surgically
      treated at our institute from January 2010 to December 2016. Patients included
      were divided in two groups depending on surgery that was performed within or
      after 24 h the admission to the hospital. Neurological status was assessed with
      American Spine Injury Association (ASIA) Impairment Scale. RESULTS: No
      statistically significant difference was observed in the variation of ASIA if
      surgery is performed within or after 24 h from the admission to the hospital. A
      statistically significant difference was observed after surgery in each group in
      the improvement of neurological status. A statistically significant difference
      was reported in the early post-operative complications in patients surgically
      treated within 24 h. CONCLUSION: MESCC management is challenge for spine surgeons
      and may represent an oncologic emergency and if not promptly diagnosed can lead
      to a permanent neurological damage. According to this study, there is no
      difference in the chance of neurological recovery if surgery is performed within
      or after 24 h the admission to hospital, but there is a greater rate of early
      post-operative complications when surgery is performed within 24 h from the
      admission to the hospital.

PMID- 29600417
TI  - Reply to the letter to the editor: H. pylori test-and-treat should not be put off
      for gastric cancer prevention in East Asia any longer.

PMID- 29600418
TI  - Comparison of Model Averaging and Model Selection in Dose Finding Trials Analyzed
      by Nonlinear Mixed Effect Models.
AB  - In drug development, pharmacometric approaches consist in identifying via a model
      selection (MS) process the model structure that best describes the data. However,
      making predictions using a selected model ignores model structure uncertainty,
      which could impair predictive performance. To overcome this drawback, model
      averaging (MA) takes into account the uncertainty across a set of candidate
      models by weighting them as a function of an information criterion. Our primary
      objective was to use clinical trial simulations (CTSs) to compare model selection
      (MS) with model averaging (MA) in dose finding clinical trials, based on the AIC
      information criterion. A secondary aim of this analysis was to challenge the use
      of AIC by comparing MA and MS using five different information criteria. CTSs
      were based on a nonlinear mixed effect model characterizing the time course of
      visual acuity in wet age-related macular degeneration patients. Predictive
      performances of the modeling approaches were evaluated using three performance
      criteria focused on the main objectives of a phase II clinical trial. In this
      framework, MA adequately described the data and showed better predictive
      performance than MS, increasing the likelihood of accurately characterizing the
      dose-response relationship and defining the minimum effective dose. Moreover,
      regardless of the modeling approach, AIC was associated with the best predictive
      performances.

PMID- 29600419
TI  - Heavy Metal (Cd and Pb) and Aflatoxin Contamination in Tissues and Eggs from Free
      Grazing Ducks and Their Environment in Central Thailand.
AB  - The cross-sectional study of heavy metals and aflatoxins was conducted by
      studying duck egg, blood, liver, feed, and water samples from 11 free grazing
      farms. The duck feed, soil, and rice samples were lower than the standard limit
      for aflatoxins at 20 ng g-1. The highest levels of aflatoxin were detected in the
      liver, intestine, and egg yolk; these were 3.04, 1.73, and 4.56 ng g-1
      respectively, while the average levels were 1.6 +/- 0.73, 1.31 +/- 0.23, and 1.87
      +/- 0.99 ng g-1, respectively. Interestingly, aflatoxin was not detected in any
      of the egg white albumin samples (90/90 samples), whereas aflatoxin contamination
      was predominantly found in the yolk. Additionally, the means and standard
      deviations of Pb and Cd found in the duck eggs were 118.61 +/- 22.25 and 13.84 +/
      9.06 ng g-1 respectively. The maximum levels of Pb and Cd in eggs were 134.34
      and 29.72 ng g-1, respectively. Moreover, Pb contamination occurred in the duck
      liver tissue in 93.61% (88/94) of the samples, whereas Cd contamination was found
      in 100% (100/100). The maximum levels of Pb and Cd in the duck liver tissues were
      606.16 and 22,946.20 ng g-1, which was higher than those in the eggs. Pb
      contamination in the water from rice paddy fields after grazing was significantly
      higher than that in water samples taken before grazing. This is the first report
      of Pb and Cd contamination in blood, egg, and liver samples of free grazing ducks
      in Thailand.

PMID- 29600420
TI  - Efficacy and safety of decitabine against cutaneous granuloblastic sarcoma: a
      case report.

PMID- 29600421
TI  - Combined robot assisted right partial nephrectomy and cholecystectomy with single
      docking.
AB  - AlphaBSTRACT: We report the first case of robot-assisted partial nephrectomy
      (RARN) and Robot assisted cholecystectomy in a 66 years old female overweight
      patient with organ-confined right kidney tumor identified on the investigation of
      gastrointestinal symptoms with a single docking. A modified position of the
      patient and a slight altered placement of the trocars made feasible the
      concomitant performance of the two operations. Total blood loss was 80 ml,
      operation time was 253 min and console time 187 min. The drain was removed on
      second post-operative day and the patient was discharged at the 3rd post
      operative day. Using a single docking of the da Vinci S system, intraoperative
      time and cost are minimized in patients with both organ-confined kidney tumors
      and gall bladder stones.

PMID- 29600422
TI  - Balloon and Coil Occlusion of a Superior Sagittal Sinus Cortical Vein Facilitates
      Percutaneous Supraorbital Venous Malformation Sclerotherapy.
AB  - Venous malformations are the most common of all vascular anomalies. Venous
      malformations are treated using a multidisciplinary approach with sclerotherapy
      representing the primary treatment modality. While rare, sclerotherapy in the
      central nervous system carries the risk of venous thrombosis, non-target
      embolization, and venous infarction and hemorrhage. Options for controlling
      venous outflow when treating venous malformations in the head and neck are
      limited. This report details the use of balloon and coil occlusion of a superior
      sagittal sinus cortical vein to facilitate percutaneous sclerotherapy of a
      supraorbital venous malformation.

PMID- 29600423
TI  - Travel Time to Clinic but not Neighborhood Crime Rate is Associated with
      Retention in Care Among HIV-Positive Patients.
AB  - Using geospatial analysis, we examined the relationship of distance between a
      patient's residence and clinic, travel time to clinic, and neighborhood violent
      crime rates with retention in care or viral suppression among people living with
      HIV (PLWH). For HIV-positive patients at a large urban clinic, we measured
      distance and travel time between home and clinic and violent crime rate within a
      two block radius of the travel route. Kruskal-Wallis rank sum was used to compare
      outcomes between groups. Over the observation period, 2008-2016, 219/602 (36%)
      patients were retained in care. Median distance from clinic was 3.6 (IQR 2.1-5.6)
      miles versus 3.9 (IQR 2.7-6.1) miles among those retained versus not retained in
      care, p = 0.06. Median travel time by car was 15.9 (IQR 9.6-22.9) versus 17.1
      (IQR 12.0-24.6) minutes for those retained versus not retained, p = 0.04. Violent
      crime rate along travel route was not associated with retention. There was no
      significant association between travel time or distance and viral suppression.

PMID- 29600424
TI  - Comparison of Ice Hockey Goaltender Helmets for Concussion Type Impacts.
AB  - Concussions are among the most common injuries sustained by ice hockey
      goaltenders and can result from collisions, falls and puck impacts. However, ice
      hockey goaltender helmet certification standards solely involve drop tests to a
      rigid surface. This study examined how the design characteristics of different
      ice hockey goaltender helmets affect head kinematics and brain strain for the
      three most common impact events associated with concussion for goaltenders. A
      NOCSAE headform was impacted under conditions representing falls, puck impacts
      and shoulder collisions while wearing three different types of ice hockey
      goaltender helmet models. Resulting linear and rotational acceleration as well as
      maximum principal strain were measured for each impact condition. The results
      indicate that a thick liner and stiff shell material are desirable design
      characteristics for falls and puck impacts to reduce head kinematic and brain
      tissue responses. However for collisions, the shoulder being more compliant than
      the materials of the helmet causes insufficient compression of the helmet
      materials and minimizing any potential performance differences. This suggests
      that current ice hockey goaltender helmets can be optimized for protection
      against falls and puck impacts. However, given collisions are the leading cause
      of concussion for ice hockey goaltenders and the tested helmets provided little
      to no protection, a clear opportunity exists to design new goaltender helmets
      which can better protect ice hockey goaltenders from collisions.

PMID- 29600425
TI  - A novel bispecific antibody fusion protein co-targeting EGFR and CD47 with
      enhanced therapeutic index.
AB  - OBJECTIVE: To promote targeting specificity of anti-CD47 agents, we have
      constructed a novel bispecific antibody fusion protein against EGFR and CD47,
      which may minimize the "off-target" effects caused by CD47 expression on red
      blood cells. RESULTS: The novel bispecific antibody fusion protein, denoted as Bi
      SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis
      stimulation effects in vitro. Bi-SP treatment with a low dose more effectively
      inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRPalpha
      variant-Fc (SIRPalphaV-Fc) in the A431 xenograft tumor model. In addition, the
      treatment with Bi-SP produced less red blood cell (RBC) losses than the
      SIRPalphaV-Fc treatment, suggesting its potential use for minimizing RBC toxicity
      in therapy. CONCLUSIONS: Bi-SP with improved therapeutic index has the potential
      to treat CD47+ and EGFR+ cancers in clinics.

PMID- 29600426
TI  - Antibiotic-induced fever in orthopaedic patients-a diagnostic challenge.
AB  - INTRODUCTION: Antibiotic-induced fever is a probably underestimated complication,
      which may be misdiagnosed as new infection. In this study, characteristics,
      diagnostic approach, and outcome of antibiotic-induced fever in patients treated
      for musculoskeletal infections are described. METHODS: We retrospectively
      reviewed all patients with antibiotic-induced fever after surgery treated at our
      institution from 2014 to 2017. Antibiotic-induced fever was diagnosed, if the
      following criteria were fulfilled: (i) central (ear) body temperature > 38.0 
      degrees C; (ii) intravenous antibiotics for > three days; (iii) exclusion of
      infectious or other non-infectious causes of fever; and (iv) defervescence after
      discontinuation of antibiotics. RESULTS: We included 11 patients (median age 51
      years) treated for infection after fracture fixation (n = 5), periprosthetic
      joint infections (n = 3), infection after spinal instrumentation (n = 1), and
      soft tissue infection (n = 2). The suspected antibiotics inducing fever were beta
      lactam antibiotics (n = 9), vancomycin (n = 3), daptomycin (n = 2), clindamycin,
      and meropenem (n = 1 each). Additional clinical findings were reduced general
      condition, generalized exanthema, and rigors, whereas five patients were
      asymptomatic apart from a fever. Leukopenia was observed in nine patients and
      increase of C-reactive protein value in ten patients. Fever occurred after a
      median of 20 days of antibiotic treatment and resolved after a median of one day
      after discontinuation of the suspected antibiotic. CONCLUSIONS: Antibiotics
      should be considered as the possible cause of fever in orthopaedic patients
      receiving antimicrobial treament whenever clinical signs of new or persisting
      infection are lacking. Important hints suggestive for antibiotic-induced fever
      are good general condition despite high temperature and progressive leukopenia.
      Discontinuation or change to another substance leads to prompt defervescence,
      preventing unnecessary diagnostic procedures and antibiotic treatment.

PMID- 29600427
TI  - PAS positivity of erythroid precursor cells is associated with a poor prognosis
      in newly diagnosed myelodysplastic syndrome patients.
AB  - Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders
      characterized by hematopoietic insufficiency. The accurate risk stratification of
      patients with MDS is essential for selection of appropriate therapies. We herein
      conducted a retrospective cohort study to examine the prognostic value of
      periodic acid-Schiff (PAS) reaction-positive erythroblasts in MDS patients. We
      examined the PAS positivity of the bone marrow erythroblasts of 144 patients
      newly diagnosed with MDS; 26 (18.1%) of them had PAS-positive erythroblasts,
      whereas 118 (81.9%) did not. The PAS-positive group showed significantly poorer
      karyotypes as defined in the revised International Prognostic Scoring System
      (IPSS-R) and higher scores in age-adjusted IPSS-R (IPSS-RA) than the PAS-negative
      group. Overall survival (OS) and leukemia-free survival (LFS) were also
      significantly shorter in the PAS-positive group than in the PAS-negative group.
      Similar results were obtained when only high- and very high risk groups were
      analyzed using IPSS-RA. This retrospective study suggested that the PAS
      positivity of erythroblasts is an additional prognostic factor combined with
      other risk scores for OS and LFS in MDS, and our results may contribute to
      improved clinical decision-making and rapid risk stratification.

PMID- 29600428
TI  - CBL mutation and MEFV single-nucleotide variant are important genetic predictors
      of tumor reduction in glucocorticoid-treated patients with chronic myelomonocytic
      leukemia.
AB  - Glucocorticoid (GC) therapy occasionally relieves tumor-related fever and
      promotes tumor reduction in patients with chronic myelomonocytic leukemia (CMML).
      A mutation analysis of 24 patients with CMML revealed the relationship of GC
      effectiveness, defined as a monocyte reduction of > 50% within 3 days of
      methylprednisolone administration, with the MEFV single-nucleotide variant (SNV)
      and CBL mutation. Lipopolysaccharide-stimulated monocytes harboring MEFV E148Q
      produced greater amounts of IL-1beta and TNF-alpha than did wild-type monocytes;
      this was effectively suppressed by GC. Primary CMML cells harboring the MEFV SNV
      and CBL mutation, and the myelomonocytic leukemia cell line GDM-1, harboring the
      CBL mutation, were both more significantly suppressed than non-mutated cells
      following GC treatment in the presence of GM-CSF. A loss-of-function CBL mutation
      prolonged STAT5 phosphorylation after GM-CSF stimulation, which was rapidly
      terminated in both patient samples and GDM-1 cells. In conclusion, GC therapy
      effectively treats CMML cells harboring the MEFV SNV and CBL mutation by reducing
      inflammatory cytokine production and terminating prolonged STAT5 phosphorylation
      in the GM-CSF signaling pathway.

PMID- 29600429
TI  - Efficacy and safety of ledipasvir/sofosbuvir for genotype 1b chronic hepatitis C
      patients with moderate renal impairment.
AB  - BACKGROUND/AIM: To evaluate the efficacy and safety of ledipasvir and sofosbuvir
      therapy for genotype 1b in chronic hepatitis C patients with chronic kidney
      disease (CKD) stage 3. METHODS: In a multicenter collaborative retrospective
      study, 706 patients who have received ledipasvir which is NS5A inhibitor, and
      sofosbuvir 400 mg which is NS5B nucleoside polymerase inhibitor daily for 12
      weeks between September 2015 and January 2017 were subjected to this analysis.
      Virologic response and adverse events in patients with CKD stage 3 were compared
      with those in patients with CKD stages 1 and 2. RESULTS: The rates of sustained
      virologic response (SVR) were 97.0% in patients with CKD stage 1, 97.1% in
      patients with CKD stage 2, and 94.7% in patients with CKD stage 3, respectively.
      There were no significant differences in the SVR rates between CKD stages 1 and
      2, and CKD stage 1 and stage 3. The incidence of adverse events over than grade 2
      was 0% in patients with CKD stage 1, 0.5% in patients with CKD stage 2, and 3.0%
      in patients with CKD stage 3, respectively. For treatment and follow-up period,
      eGFR levels in the patients with CKD stage 3 were not worsened compared to those
      at baseline. CONCLUSION: This study suggested that the virologic response of
      ledipasvir and sofosbuvir in patients with CKD stage 3 was not inferior to those
      with CKD stages 1 and 2. In addition, administration of ledipasvir and sofosbuvir
      did not affect eGFR levels in the patients with CKD stage 3.

PMID- 29600430
TI  - Targeting incretin hormones and the ASK-1 pathway as therapeutic options in the
      treatment of non-alcoholic steatohepatitis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms
      of chronic liver disease, and its rising frequency worldwide has reached epidemic
      proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic
      steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The
      pathophysiologic mechanisms that contribute to the development and progression of
      NAFLD and NASH are complex, and as such myriad therapies are under investigation
      targeting different pathophysiological mechanisms. Incretin-based therapies,
      including GLP-1RAs and DPP-4 inhibitors and the inhibition of ASK1 pathway have
      provided two such novel mechanisms in the management of this disease, and will
      remain focus of this review.

PMID- 29600432
TI  - Catheter probe extraductal ultrasound (EDUS) exploration of the common bile duct
      is safe in elderly patients with suspicion of choledocholithiasis after distal
      gastrectomy.
AB  - PURPOSE: Post-surgical upper gastrointestinal anatomy may hamper a complete bilio
      pancreatic evaluation with a standard echoendoscope. The aim of this study was to
      assess the role of catheter probe extraductal ultrasound (EDUS) for the
      evaluation of the common bile duct (CBD) in patients who are status post-gastric
      surgery and who are suspected of having choledocholithiasis. METHODS: We
      retrospectively analyzed patients with a prior history of gastric surgery, who
      underwent EDUS for a suspicion of CBD obstruction. For each patient, technical
      success, accuracy, and safety were recorded. In case of a positive finding of CBD
      stones, endoscopic retrograde cholangiopancreatography (ERCP) was performed. In
      case of other findings or a negative EDUS, computed tomography or magnetic
      resonance cholangiopancreatography (MRCP) was performed as appropriate. RESULTS:
      EDUS was technically successful in all the 11 patients with a Billroth II
      gastrectomy, while it failed in all the 5 patients with Roux-en-Y gastric
      surgery. EDUS accuracy was 100% (3 true-positive and 8 true-negative cases). CBD
      stones, confirmed and successfully extracted at ERCP, were found in two patients,
      while in one patient EDUS showed a CBD stenosis that was treated with a plastic
      stent during ERCP; computed tomography at follow-up was negative for cancer. EDUS
      was correctly negative in 8 patients, as confirmed by MRCP. CONCLUSIONS: EDUS may
      represent an accurate and safe alternative to standard endoscopic ultrasonography
      and MRCP for the detection of CBD stones in elderly patients who are status post
      Billroth II gastric surgery.

PMID- 29600431
TI  - Effectiveness of arginase inhibitors against experimentally induced stroke.
AB  - Stroke is a lethal disease, but it disables more than it kills. Stroke is the
      second leading cause of death and the most frequent cause of permanent disability
      in adults worldwide, with 90% of survivors having residual deficits. The
      pathophysiology of stroke is complex and involves a strong inflammatory response
      associated with oxidative stress and activation of several proteolytic enzymes.
      The current study was designed to investigate the effect of arginase inhibitors
      (L-citruline and L-ornithine) against ischemic stroke induced in rats by middle
      cerebral artery occlusion (MCAO). MCAO resulted in alteration in rat behavior,
      brain infarct, and edema associated with disruption of the blood-brain barrier
      (BBB). This was mediated through overexpression of arginase I and II, inducible
      NOS (iNOS), malondialdehyde (MDA), advanced glycation end products (AGEs), TNF
      alpha, and IL-1beta and downregulation of endothelial nitric oxide synthase
      (eNOS). Treatment with L-citruline and L-ornithine and the standard
      neuroprotective drug cerebrolysin ameliorated all the deleterious effects of
      stroke. These results indicate the possible use of arginase inhibitors in the
      treatment of stroke after suitable clinical trials are done.

PMID- 29600434
TI  - Environmental Behavior Among Russian Youth: The Role of Self-direction and
      Environmental Concern.
AB  - Previous research that has tried to identify the personal values that best
      explain variance in pro-environmental attitudes tended to focus on biospheric and
      universalism values. This paper examines the importance of self-direction as a
      value underlying young people's inclination to adopt pro-environmental behaviors
      and environmental activism. We expect that individuals who emphasize a self
      direction value, which fosters creativity, motivates innovation, and promotes
      coping with challenges, are likely to respond in more self-directed and
      autonomous ways to emerging environmental practices. We analyze a sample of 600
      university students surveyed in Moscow and find that biospheric and self
      direction values are associated with environmental behavior and activism. Beyond
      the direct effect of self-direction value on pro-environmental behaviors and
      environmental activism we also observe a moderation effect of self-direction on
      the association between concern and environmental behavior. We discuss the
      implications of our findings for encouraging environmental action in specific
      contexts, similar to the one depicted in our sample.

PMID- 29600433
TI  - Estrogen therapy in patients with prostate cancer: a contemporary systematic
      review.
AB  - PURPOSE: To evaluate the effectiveness and harms of DES in treating prostate
      cancer compared to other forms of androgen deprivation therapy (orchiectomy, LHRH
      agonists, and anti-androgens). METHODS: We included clinical trials comparing DES
      with other forms of ADT (bicalutamide, flutamide, LHRH agonists, or orchiectomy)
      in PCa treatment. The primary outcomes were overall survival, cancer-specific
      survival, and progression-free survival, and secondary outcomes were
      cardiovascular effects. We searched in MEDLINE, EMBASE, Central, and Lilacs from
      inception to nowadays and saturated information for unpublished data in other
      sources. We performed a qualitative analysis of all included studies. It was not
      possible to perform meta-analysis due to low-quality trials and high
      heterogeneity. RESULTS: Overall, 1700 references were scanned and 14 prospective
      randomized trials with a total of 3986 patients were included in the final
      analysis. Although trials showed DES as similarly effective to another forms of
      ADT, evidences about cardiovascular toxicity in out of date high doses have
      discouraged its use. In doses of 1 mg, DES has been used as secondary line PCa
      treatment with safety. CONCLUSIONS: DES might be similarly effective to other
      forms of ADT on advanced PCa patients, with potential important roles.
      Intriguingly, the burden of severe cardiovascular toxicity is mainly related to
      old-fashioned doses of 5.0 and 3.0 mg. Modern PCa hormonal knowledge warrants
      stout high-quality prospective randomized trials in the low-dose 1 mg DES
      scenario.

PMID- 29600435
TI  - Putting Climate Adaptation on the Map: Developing Spatial Management Strategies
      for Whitebark Pine in the Greater Yellowstone Ecosystem.
AB  - Natural resource managers face the need to develop strategies to adapt to
      projected future climates. Few existing climate adaptation frameworks prescribe
      where to place management actions to be most effective under anticipated future
      climate conditions. We developed an approach to spatially allocate climate
      adaptation actions and applied the method to whitebark pine (WBP; Pinus
      albicaulis) in the Greater Yellowstone Ecosystem (GYE). WBP is expected to be
      vulnerable to climate-mediated shifts in suitable habitat, pests, pathogens, and
      fire. We spatially prioritized management actions aimed at mitigating climate
      impacts to WBP under two management strategies: (1) current management and (2)
      climate-informed management. The current strategy reflected management actions
      permissible under existing policy and access constraints. Our goal was to
      understand how consideration of climate might alter the placement of management
      actions, so the climate-informed strategies did not include these constraints.
      The spatial distribution of actions differed among the current and climate
      informed management strategies, with 33-60% more wilderness area prioritized for
      action under climate-informed management. High priority areas for implementing
      management actions include the 1-8% of the GYE where current and climate-informed
      management agreed, since this is where actions are most likely to be successful
      in the long-term and where current management permits implementation. Areas where
      climate-informed strategies agreed with one another but not with current
      management (6-22% of the GYE) are potential locations for experimental testing of
      management actions. Our method for spatial climate adaptation planning is
      applicable to any species for which information regarding climate vulnerability
      and climate-mediated risk factors is available.

PMID- 29600436
TI  - Amino acid adsorption on anatase (101) surface at vacuum and aqueous solution: a
      density functional study.
AB  - The adsorption of 20 amino acids (AAs) on the (101) surface of anatase titanium
      dioxide (TiO2) has been investigated under the scheme of density functional
      theory. Through the analysis of adsorption geometries, amino group and side
      chains of AAs have been identified as the major side to adsorb on TiO2, while the
      carboxyl group prefers to stay outside to avoid the repulsion between negatively
      charged oxygen from TiO2 and AAs. On the surface, two-coordinated oxygen is the
      major site to stabilize AAs through O-H interactions. The above conclusion does
      not change when it is in the aqueous solution based on the calculations with AAs
      surrounded by explicit water molecules. The above knowledge is helpful in
      predicting how AAs and even peptides adsorb on inorganic materials. Graphical
      abstract The adsorption of 20 amino acids (AAs) on the (101) surface of anatase
      titanium dioxide (TiO2) has been investigated under the scheme of density
      functional theory.

PMID- 29600437
TI  - CBS mutations and MTFHR SNPs causative of hyperhomocysteinemia in Pakistani
      children.
AB  - Three index patients with hyperhomocysteinemia and ocular anomalies were screened
      for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase
      (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR
      polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR
      restriction fragment length polymorphism. Sanger sequencing was performed for CBS
      exonic sequences along with consensus splice sites. In the case of MTHFR
      polymorphisms, all the patients were heterozygous CT for the single nucleotide
      polymorphism (SNP) C677T and were therefore carriers of the risk allele (T),
      while the patients were homozygous CC for the risk genotype of the SNP A1298C.
      CBS sequencing resulted in the identification of two novel mutations, a missense
      change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del;
      p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T;
      p.Thr257Met) in exon 10 of the gene was also identified. The mutations were
      present homozygously in the patients and were inherited from the carrier parents.
      This is the first report from Pakistan where novel as well as recurrent CBS
      mutations causing hyperhomocysteinemia and lens dislocation in three patients
      from different families are being reported with the predicted effect of the risk
      allele of the MTHFR SNP in causing hyperhomocysteinemia.

PMID- 29600438
TI  - Functionalization of PLGA Nanoparticles with 1,3-beta-glucan Enhances the
      Intracellular Pharmacokinetics of Rifampicin in Macrophages.
AB  - PURPOSE: Mycobacterium tuberculosis which causes tuberculosis, is primarily
      resident within macrophages. 1,3-beta-glucan has been proposed as a ligand to
      target drug loaded nanoparticles (NPs) to macrophages. In this study we
      characterized the intracellular pharmacokinetics of the anti-tubercular drug
      rifampicin delivered by 1,3-beta-glucan functionalized PLGA NPs (Glu-PLGA). We
      hypothesized that Glu-PLGA NPs would be taken up at a faster rate than PLGA NPs,
      and consequently deliver higher amounts of rifampicin into the macrophages.
      METHODS: Carbodiimide chemistry was employed to conjugate 1,3-beta-glucan and
      rhodamine to PLGA. Rifampicin loaded PLGA and Glu-PLGA NPs as well as rhodamine
      functionalized PLGA and Glu-PLGA NPs were synthesized using an emulsion solvent
      evaporation technique. Intracellular pharmacokinetics of rifampicin and NPs were
      evaluated in THP-1 derived macrophages. A pharmacokinetic model was developed to
      describe uptake, and modelling was performed using ADAPT 5 software. RESULTS: The
      NPs increased the rate of uptake of rifampicin by a factor of 17 and 62 in case
      of PLGA and Glu-PLGA, respectively. Expulsion of NPs from the macrophages was
      also observed, which was 3 fold greater for Glu-PLGA NPs than for PLGA NPs.
      However, the ratio of uptake to expulsion was similar for both NPs. After 24 h,
      the amount of rifampicin delivered by the PLGA and Glu-PLGA NPs was similar. The
      NPs resulted in at least a 10-fold increase in the uptake of rifampicin.
      CONCLUSIONS: Functionalization of PLGA NPs with 1,3-beta-glucan resulted in
      faster uptake of rifampicin into macrophages. These NPs may be useful to achieve
      rapid intracellular eradication of Mycobacterium tuberculosis.

PMID- 29600439
TI  - Assessment of dietary calcium intake of university students: a pilot study in
      Turkey.
AB  - : The aim of this study was to adapt the rapid assessment method (RAM) and
      International Osteoporosis Foundation Food Frequency Questionnaire (IOF FFQ)
      tools, used for the assessment of daily calcium intake in university students,
      and to compare the data obtained using 24-h recall (24-HR) data. There was a
      moderate positive correlation between the RAM and IOF. PURPOSE/INTRODUCTION:
      Calcium is an essential mineral that plays vital roles in metabolism and it is
      very important to accurately assess the amount of calcium intake on the diet. It
      was aimed to assess the daily calcium intake of university students by two
      different food frequency questionnaires (FFQs) developed specifically for
      evaluating calcium intake, and 24-h recall method. METHOD: The study was
      conducted with a total of 183 female university students aged 18-31. In the
      study, a questionnaire including sociodemographic information, a calcium
      calculator, IOF FFQ, prepared in seven different languages, and RAM was applied.
      In addition, 1-day food consumption records were obtained using 24-HR method.
      RESULTS: The daily average calcium intakes of individuals according to two
      different food frequency questionnaires (RAM FFQ and IOF FFQ) and 24-h food
      consumption records are respectively 1594.2 +/- 810.9, 897.9 +/- 368.4, and 605.6
      +/- 278.3 mg. When the daily average calcium intake was compared with the other
      two methods, RAM was found to be statistically higher (p < 0.001). There was a
      moderate positive correlation between the RAM and IOF FFQ methods (Pearson r =
      0.528, p < 0.01) and the intra-class correlation coefficient between these two
      methods was found to be significant and moderate (ICC r = 0.452, p < 0.01).
      CONCLUSION: In terms of protecting and improving health, it is important to make
      suggestions using fast and short tools to ensure adequate calcium intake from
      young age. It is thought that FFQs are the most appropriate methods in assessing
      daily calcium intake for this study group because it is observed that the list of
      foods and the amount of portions in FFQs reduce the problem of remembering at 24
      h method to a great extent.

PMID- 29600440
TI  - Identifying key areas of ecosystem services potential to improve ecological
      management in Chongqing City, southwest China.
AB  - Because natural ecosystems and ecosystem services (ES) are both critical to the
      well-being of humankind, it is important to understand their relationships and
      congruence for conservation planning. Spatial conservation planning is required
      to set focused preservation priorities and to assess future ecological
      implications. This study uses the combined measures of ES models and ES potential
      to estimate and analyze all four groups of ecosystem services to generate
      opportunities to maximize ecosystem services. Subsequently, we identify the key
      areas of conservation priorities as future forestation and conservation hotspot
      zones to improve the ecological management in Chongqing City, located in the
      upper reaches of the Three Gorges Reservoir Area, China. Results show that
      ecosystem services potential is extremely obvious. Compared to ecosystem services
      from 2000, we determined that soil conservation could be increased by 59.11%,
      carbon sequestration by 129.51%, water flow regulation by 83.42%, and water
      purification by 84.42%. According to our prioritization results, approximately
      48% of area converted to forests exhibited high improvements in all ecosystem
      services (categorized as hotspot-1, hotspot-2, and hotspot-3). The hotspots
      identified in this study can be used as an excellent surrogate for evaluation
      ecological engineering benefits and can be effectively applied in improving
      ecological management planning.

PMID- 29600441
TI  - Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010.
AB  - Multiple sclerosis treatment faces tremendous changes as a result of the approval
      of new medications. The new medications have differing safety considerations and
      risks after long-term treatment, which are important for treating physicians to
      optimize and individualize multiple sclerosis care. Since the approval of the
      first multiple sclerosis capsule, fingolimod, the armamentarium of multiple
      sclerosis therapy has grown with the orally available medications dimethyl
      fumarate and teriflunomide. Fingolimod is mainly associated with cardiac side
      effects, dimethyl fumarate with bowel symptoms. Several reports about progressive
      multifocal leukoencephalopathy as a result of dimethyl fumarate or fingolimod
      therapy raised the awareness of fatal opportunistic infections. Alemtuzumab, a
      CD52-depleting antibody, is highly effective in reducing relapses but leads to
      secondary immunity with mainly thyroid disorders in about 30% of patients.
      Development of secondary B-cell-mediated disease might also be a risk of this
      antibody. The follow-up drug of the B-cell-depleting antibody rituximab,
      ocrelizumab, is mainly associated with infusion-related reactions; long-term data
      are scarce. The medication daclizumab high yield process, acting via the
      activation of CD56bright natural killer cells, can induce the elevation of liver
      function enzymes, but also fulminant liver failure has been reported. Therefore,
      daclizumab has been retracted from the market. Long-term data on the purine
      nucleoside cladribine in MS therapy, recently authorized in the European Union,
      have been acquired during the long-term follow-up of the cladribine studies. The
      small molecule laquinimod is currently under development. We review data of
      clinical trials and their extensions regarding long-term efficacy and side
      effects, which might be associated with long-term treatment.

PMID- 29600442
TI  - Spectrally decomposed dark-to-light transitions in Synechocystis sp. PCC 6803.
AB  - Photosynthetic activity and respiration share the thylakoid membrane in
      cyanobacteria. We present a series of spectrally resolved fluorescence
      experiments where whole cells of the cyanobacterium Synechocystis sp. PCC 6803
      and mutants thereof underwent a dark-to-light transition after different dark
      adaptation (DA) periods. Two mutants were used: (i) a PSI-lacking mutant
      (DeltaPSI) and (ii) M55, a mutant without NAD(P)H dehydrogenase type-1 (NDH-1).
      For comparison, measurements of the wild-type were also carried out. We recorded
      spectrally resolved fluorescence traces over several minutes with 100 ms time
      resolution. The excitation light was at 590 nm so as to specifically excite the
      phycobilisomes. In DeltaPSI, DA time has no influence, and in dichlorophenyl
      dimethylurea (DCMU)-treated samples we identify three main fluorescent
      components: PB-PSII complexes with closed (saturated) RCs, a quenched or open PB
      PSII complex, and a PB-PSII 'not fully closed.' For the PSI-containing organisms
      without DCMU, we conclude that mainly three species contribute to the signal: a
      PB-PSII-PSI megacomplex with closed PSII RCs and (i) slow PB -> PSI energy
      transfer, or (ii) fast PB -> PSI energy transfer and (iii) complexes with open
      (photochemically quenched) PSII RCs. Furthermore, their time profiles reveal an
      adaptive response that we identify as a state transition. Our results suggest
      that deceleration of the PB -> PSI energy transfer rate is the molecular
      mechanism underlying a state 2 to state 1 transition.

PMID- 29600443
TI  - Immuno-receptors: from recognition to signaling and function.
AB  - The vertebrate adaptive immune response is initiated by specific recognition of
      antigens. This is carried out by molecules, soluble or cell surface receptors
      that are members of the Multichain Immune Recognition Receptors (MIRR) group of
      proteins. The soluble arm of the response is based on antibodies. Kinetic
      analysis of antibody-antigenic epitope interactions pioneered insights into the
      complexity underlying the capacity of relatively limited repertoires of
      antibodies to recognize an essentially unlimited range of epitopes by employing
      conformational diversity of a given single sequence. The arm responsible for
      recognition of cellular targets involves a considerably more elaborate process,
      predominantly of antigen-derived peptides presented bound to molecules encoded by
      the major histocompatibility complex (MHC). This remarkable cellular recognition
      process performed by T-cell receptors requires earlier steps of peptide
      presentation and involves interactions of the receptor sites with the array of
      its MHC-peptide composite ligand. In both cases, antigen recognition needs to be
      followed by its coupling, by biochemical cascades, to different specific
      responses, namely activation of effector functions. The parameters required for
      coupling to functional responses are still a focus of intense research. In
      solution, antigen-antibody aggregation is one established activation process.
      Those required for coupling antigen recognition to cell activation, whether by Fc
      receptor bound antibodies or by the B-cell antigen receptor, are also still
      subject to active research efforts. Though activation by immune-receptors
      requires antigen recognition, considerable differences could exist among the
      requirements set by distinct cell types. Moreover, antigen binding requiring
      intercellular interactions introduces additional complexity.

PMID- 29600446
TI  - A Simple and Useful Method to Apply Exogenous NO Gas to Plant Systems: Bell
      Pepper Fruits as a Model.
AB  - Nitric oxide (NO) is involved many physiological plant processes, including
      germination, growth and development of roots, flower setting and development,
      senescence, and fruit ripening. In the latter physiological process, NO has been
      reported to play an opposite role to ethylene. Thus, treatment of fruits with NO
      may lead to delay ripening independently of whether they are climacteric or
      nonclimacteric. In many cases different methods have been reported to apply NO to
      plant systems involving sodium nitroprusside, NONOates, DETANO, or GSNO to
      investigate physiological and molecular consequences. In this chapter a method to
      treat plant materials with NO is provided using bell pepper fruits as a model.
      This method is cheap, free of side effects, and easy to apply since it only
      requires common chemicals and tools available in any biology laboratory.

PMID- 29600444
TI  - Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients
      with normal and mildly elevated ALT.
AB  - PURPOSE: YKL-40 is a chitinase-like protein expressed in multiple tissues
      including liver and is reported as a fibrosis marker. This study aimed to
      determine whether YKL-40 could serve as a diagnostic marker for the assessment of
      liver fibrosis in chronic hepatitis B patients with normal and mildly elevated
      ALT. METHODS: Six hundred and eighty-five patients with chronic hepatitis B
      infection were enrolled in this study from October 2013 to March 2016. All
      patients underwent liver biopsy and then staged based on Ishak histological
      system. Serum YKL-40 levels were measured by Human Magnetic Luminex Assays.
      RESULTS: Among chronic hepatitis B patients with normal and mildly elevated ALT,
      almost more than 30% of patients have significant liver fibrosis. Serum YKL-40
      levels increased significantly in parallel with the progression of fibrosis in
      patients with ALT less than two times the upper limit of normal range (P <
      0.0001). Multivariate analysis revealed that serum YKL-40, hyaluronic acid, PLT,
      and AST were independently associated with significant fibrosis. We established a
      novel YKL-40-based fibrosis model for patients with ALT less than two times the
      upper limit of normal range (ULN). YKL-40 model was superior to APRI, FIB-4,
      Forns' index, and Hui model for diagnosis of significant fibrosis in patients
      with ALT < 2ULN, with AUROCs of 0.786 [95% confidence interval (CI) 0.726-0.846]
      in the training group, 0.831 (95%CI 0.752-0.910) in the validation group and
      0.801 (95%CI 0.753-0.849) in the entire cohort. CONCLUSION: Serum YKL-40 is a
      feasible biomarker of liver fibrosis in chronic hepatitis B patients. YKL-40
      model was superior to APRI, FIB-4, Forns' index and Hui model for diagnosis of
      significant fibrosis in patients with normal and mildly elevated ALT.

PMID- 29600447
TI  - Measurements of Intra-oocyte Nitric Oxide Concentration Using Nitric Oxide
      Selective Electrode.
AB  - Precise information about the intracell nitric oxide (NO) concentration [NO] of a
      single cell are necessary in designing accurate experiments to further knowledge
      and develop treatment plans in certain disorders. The direct quantitative
      measurement of [NO] in situ in an intact cellular complex should be useful in
      tracking real-time and rapid changes at nanomolar levels. In this work, we
      describe the direct, real-time, and quantitative intracellular [NO] measurement
      utilizing an L-shaped amperometric integrated NO-selective electrode. This method
      not only provides an elegant and convenient approach to real-time the measurement
      of NO in physiological environments but also mimics the loss of NO caused by
      rapid NO diffusion combined with its reactivity in the biological milieu.

PMID- 29600445
TI  - Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.
AB  - Immunotherapy based on checkpoint blockers has proven survival benefits in
      patients with melanoma and other malignancies. Nevertheless, a significant
      proportion of treated patients remains refractory, suggesting that in combination
      with active immunizations, such as cancer vaccines, they could be helpful to
      improve response rates. During the last decade, we have used dendritic cell (DC)
      based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell
      lysate were tested in a series of clinical trials. In these studies, 60% of stage
      IV melanoma DC-treated patients showed immunological responses correlating with
      improved survival. Further studies showed that an essential part of the clinical
      efficacy was associated with the use of conditioned lysates. Gallbladder cancer
      (GBC) is a high-incidence malignancy in South America. Here, we evaluated the
      feasibility of producing effective DCs using heat-conditioned cell lysates
      derived from gallbladder cancer cell lines (GBCCL). By characterizing nine
      different GBCCLs and several fresh tumor tissues, we found that they expressed
      some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and
      several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs
      induced calreticulin translocation and release of HMGB1 and ATP, both known to
      act as danger signals. Monocytes stimulated with combinations of conditioned
      lysates exhibited a potent increase of DC-maturation markers. Furthermore,
      conditioned lysate-matured DCs were capable of strongly inducing CD4+ and CD8+ T
      cell activation, in both allogeneic and autologous cell co-cultures. Finally, in
      vitro stimulated CD8+ T cells recognize HLA-matched GBCCLs. In summary, GBC cell
      lysate-loaded DCs may be considered for future immunotherapy approaches.

PMID- 29600448
TI  - Real-Time Imaging of Nitric Oxide Signals in Individual Cells Using geNOps.
AB  - Nitric oxide (NO*) is a versatile signaling molecule which regulates fundamental
      cellular processes in all domains of life. However, due to the radical nature of
      NO* it has a very short half-life that makes it challenging to trace its
      formation, diffusion, and degradation on the level of individual cells. Very
      recently, we expanded the family of genetically encoded sensors by introducing a
      novel class of single fluorescent protein-based NO* probes-the geNOps. Once
      expressed in cells of interest, geNOps selectively respond to NO* by fluorescence
      quench, which enables real-time monitoring of cellular NO* signals. Here, we
      describe detailed methods suitable for imaging of NO* signals in mammalian cells.
      This novel approach may facilitate a broad range of studies to (re)investigate
      the complex NO* biochemistry in living cells.

PMID- 29600449
TI  - Detection of Nitric Oxide by Membrane Inlet Mass Spectrometry.
AB  - Membrane inlet mass spectrometry (MIMS) is a reproducible and reliable method for
      the measurement of nitric oxide in aqueous solution with a lower limit of
      detection of 10 nM and a linear response to 50 MUM. MIMS utilizes a semipermeable
      membrane to partition analytes based on physicochemical properties from the bulk
      sample into the mass spectrometer. Silastic tubing allows the introduction of
      small gaseous molecules including nitric oxide (NO) into the high vacuum of a
      mass spectrometer. We describe the measurement of NO generated chemically from
      nitrite and MAHMA NONOate as well as enzymatically by nitric oxide synthase
      (NOS).

PMID- 29600450
TI  - Quantum Cascade Lasers-Based Detection of Nitric Oxide.
AB  - Despite the established importance of nitric oxide (NO) in many physiological and
      molecular processes in plants, most methods for quantifying NO are open to
      criticism This reflects the differing methods either lacking specificity or
      sensitivity, or even from an undue dependence of results on experimental
      conditions (i.e., chemical concentrations, pH, etc.). In this chapter we describe
      a protocol to measure gaseous NO produced by a biological sample using quantum
      cascade laser (QCL)-based spectroscopy. This technique is based on absorption of
      the laser light by the NO molecules which have been passed from a biological
      sample into an optical s cell that is equipped with two mirrors placed at both
      ends. This design greatly increases the interaction path length with the NO
      molecules due to multiple reflections of the light coupled inside the cell. Thus,
      the method is able to provide online, in planta measurements of the dynamics of
      NO production, being highly selective and sensitive (down to ppbv levels;1 ppbv =
      part per billion by volume mixing ratio = 1:10-9).

PMID- 29600451
TI  - Detection of Nitric Oxide via Electronic Paramagnetic Resonance in Mollusks.
AB  - Electronic paramagnetic resonance (EPR) is an appropriate tool to identify free
      radicals formed in tissues under normal as well as stressful conditions. Since
      nitric oxide (NO) as a free radical has paramagnetic properties it can be
      detected by EPR. The use of spin traps highly improves the sensitivity allowing
      NO identification, detection and quantification at room temperature in vitro and
      in vivo conditions. NO production in animals is almost exclusively associated to
      an enzyme family known as Nitric Oxide Synthases (NOSs). The digestive glands of
      mollusks are a major target for oxidative disruption related to environmental
      stress. A simple EPR-methodology to asses both, the presence of NO and its rate
      of generation in tissues from different mollusk species, is reported here.

PMID- 29600452
TI  - Identification of S-Nitrosylated and Reversibly Oxidized Proteins by Fluorescence
      Switch and Complementary Techniques.
AB  - S-nitrosylation and other reversible oxidative posttranslational modifications of
      proteins are part of the nonclassical mechanisms of nitric oxide signaling. The
      biotin switch technique for specifically labeling S-nitrosylated proteins opened
      the way to proteomic identification of these modifications. Since then, several
      variations and adaptations of the original method have been applied.We describe
      here the protocols of several techniques that can be used for the proteomic
      identification of these modifications, as well as for the detailed
      characterization of the modification of individual proteins. The fluorescence
      switch technique allows the proteomic identification of S-nitrosylated proteins
      based on their fluorescent labeling coupled to electrophoretic separation, as
      well as the comparison of the overall modification in different samples. The
      redox fluorescence switch is an adaptation to detect all the proteins reversibly
      oxidized in cysteine residues. We also describe the protocols of complementary
      techniques that allow comparing the extent of modification of individual proteins
      in several conditions by biotin switch, and the identification of modified
      residues by differential labeling adapted for mass spectrometry identification.

PMID- 29600453
TI  - A Proteomics Workflow for Dual Labeling Biotin Switch Assay to Detect and
      Quantify Protein S-Nitroylation.
AB  - S-nitrosylation (or S-nitrosation, SNO) is an oxidative posttranslational
      modification to the thiol group of a cysteine amino acid residue. There are
      several methods to detect SNO modifications, mostly based on the classic biotin
      switch assay, where the labile SNO sites are replaced with a stable biotin moiety
      to facilitate enrichment of the modified proteins. As the technique has evolved,
      new and more advanced thiol-reactive reagents have been introduced in the
      protocol to improve the identification of modified peptides or to quantify the
      level of modification at individual cysteine residues. However, the growing
      diversity of thiol-reactive affinity tags has not produced a consistent set of
      protein modifications, suggesting incomplete coverage using a single tag. Here,
      we present a parallel dual labeling strategy followed by an optimized proteomics
      workflow, which maximizes the overall detection of SNO by reducing the labeling
      bias derived from the use of a single tag-capture approach.

PMID- 29600454
TI  - Surface Plasmon Resonance Spectroscopy for Detection of S-Nitrosylated Proteins.
AB  - Protein S-nitrosylation, the NO-dependent regulatory mechanism, is a
      posttranslational modification of reactive cysteine thiols to form S
      nitrosothiols. The biotin-switch technique (BST) has become a mainstay method for
      detection of S-nitrosylated proteins in biological samples. On the basis of BST,
      we describe a surface plasmon resonance (SPR) spectroscopy method for detecting S
      nitrosylated proteins. This method can be applied for the indirect determination
      of S-nitrosylated proteins in biological samples.

PMID- 29600455
TI  - Measurement of S -Nitrosoglutathione in Plasma by Liquid Chromatography-Tandem
      Mass Spectrometry.
AB  - This chapter describes an ultraperformance liquid chromatographic-tandem mass
      spectrometric (UPLC-MS/MS) method for the quantitative determination of S
      nitrosoglutathione (GSNO) in human plasma. S-[15N]Nitrosoglutathione (GS15NO)
      serves as the internal standard. The protocol involves inactivation of plasma
      gamma-glutamyltransferase activity by serine-borate, stabilization of GSNO with
      EDTA, and avoidance of S-transnitrosylation reactions by blocking SH groups with
      N-ethylmaleimidide (NEM). Fresh blood is treated with NEM/serine-borate/EDTA,
      plasma is spiked with GS15NO (50 nM), ultrafiltered (cutoff 10 kDa) and 10-MUL
      aliquots of ultrafiltrate are analyzed by UPLC-MS/MS in the positive electrospray
      ionization (ESI+) mode. LC is performed on a Nucleoshell column using isocratic
      (0.5 mL/min) elution with acetonitrile-20 mM ammonium formate (70:30, v/v), pH 7.
      Quantification is performed by selected-reaction monitoring the mass transition
      m/z 337 ([M+H]+) -> m/z 307 ([M+H-14NO]+?) for GSNO and m/z 338 ([M+H]+) -> m/z
      307 ([M+H-15NO]+?) for GS15NO. Matrix effects are outweighed by the internal
      standard GS15NO. The lower limit of quantitation (LOQ) is 2.8 nM.

PMID- 29600456
TI  - Analysis of Recombinant Protein S-Nitrosylation Using the Biotin-Switch
      Technique.
AB  - Nitric oxide is regarded as a key signaling messenger in several organisms. Its
      physiological relevance is partly due to its capacity to induce posttranslational
      modifications of proteins through its direct or indirect reaction with specific
      amino acid residues. Among them, S-nitrosylation has been shown to be involved in
      a broad range of cellular signaling pathways both in animals and plants. The
      identification of S-nitrosylated proteins has been made possible by the
      development of the Biotin-Switch Technique (BST) in the early 2000s. Here, we
      describe the BST protocol we routinely use to check in vitro S-nitrosylation of
      recombinant proteins induced by NO donors.

PMID- 29600457
TI  - Direct Measurement of S-Nitrosothiols with an Orbitrap Fusion Mass Spectrometer:
      S-Nitrosoglutathione Reductase as a Model Protein.
AB  - Recent studies suggest cysteine S-nitrosation of S-nitrosoglutathione reductase
      (GSNOR) could regulate protein redox homeostasis. "Switch" assays enable
      discovery of putatively S-nitrosated proteins. However, with few exceptions,
      researchers have not examined the kinetics and biophysical consequences of S
      nitrosation. Methods to quantify protein S-nitrosothiol (SNO) abundance and
      formation kinetics would bridge this mechanistic gap and allow interpretation of
      the consequences of specific modifications, as well as facilitate development of
      specific S-nitrosation inhibitors. Here, we describe a rapid assay to estimate
      protein SNO abundance with intact protein electrospray ionization mass
      spectrometry. Originally designed using recombinant GSNOR, these methods are
      applicable to any purified protein to test for or further study nitrosatable
      cysteines.

PMID- 29600458
TI  - Identification of Tyrosine and Nitrotyrosine with a Mixed-Mode Solid-Phase
      Extraction Cleanup Followed by Liquid Chromatography-Electrospray Time-of-Flight
      Mass Spectrometry in Plants.
AB  - In higher plants, there is a growing interest in the study of protein tyrosine
      nitration (NO2Tyr) as well as the identification of in vivo nitrated proteins.
      Different methods have been developed for identifying nitrotyrosine in biological
      samples. However, these analyses are difficult because tyrosine nitration is a
      very low-abundance posttranslational protein modification (PTM) and the lack of
      efficient enrichment methods for detection. The identification and quantification
      of NO2Tyr in proteins has represented a challenge for researchers.In this chapter
      a new method for determining NO2Tyr and tyrosine (Tyr) in Arabidopsis thaliana
      cell-suspension culture extracts is proposed. The quantification was performed
      using a simple, sensitive, and specific sample preparation assay based on mixed
      mode solid-phase extraction (SPE) which was developed for the quantification of
      trace NO2Tyr in Arabidopsis extracts by liquid chromatography-electrospray time
      of-flight mass spectrometry (LC-TOFMS).

PMID- 29600459
TI  - Electrophoretic Detection and Confocal Microscopic Imaging of Tyrosine Nitrated
      Proteins in Plant Tissue.
AB  - Tyrosine nitrated proteins can be detected in plant cells electrophoretically and
      their distribution can be monitored by confocal laser scanning microscopy (CLSM)
      imaging. One-dimensional polyacrylamide gel electrophoresis (1D PAGE) followed by
      Western blotting using polyclonal antibody against 3-nitrotyrosine residues
      enables detection of tyrosine nitrated proteins in plant cells. Here we describe
      detection of tyrosine nitrated proteins in the homogenates derived from sunflower
      (Helianthus annuus L.) seedling cotyledons. Total soluble proteins obtained from
      tissue homogenates are resolved using vertical gel electrophoresis followed by
      their electrophoretic transfer on to a microporous membrane support for
      immunodetection. Spatial distribution of tyrosine nitrated proteins can be
      visualized using an antibody against 3-nitrotyrosine residues. Immunofluorescent
      localization is performed by cutting 7 MUm thick wax sections of tissue followed
      by incubation in primary anti-nitrotyrosine antibody (dilution 1:200) and
      secondary Cy-3 labeled anti-rabbit IgG antibody (dilution 1:1500). Confocal laser
      scanning microscopy analysis is undertaken using argon lasers (ex: 530-550 nm and
      em: 570 nm) at pinhole 1. Modulation in the abundance and spatial localization of
      tyrosine nitrated proteins in plant tissues can be monitored using these
      techniques.

PMID- 29600460
TI  - Identification of NO-Sensitive Cysteine Residues Using Cysteine Mutants of
      Recombinant Proteins.
AB  - Nitric oxide (NO) is a free radical gas regulating a wide range of biological
      processes in plants. Proteins are the main reaction target of NO inside the
      cells. The relevance of S-nitrosation as one of the NO-mediated protein
      posttranslational modifications has been studied in detail. S-nitrosylation
      causes alterations of the activity/function, sub-cellular localization or
      interaction partners of proteins. Up to present, a large number of S-nitrosation
      candidates have been detected in plants. Recombinant proteins are widely used to
      show or confirm the protein posttranslational modifications. Here, using
      recombinant proteins subjected to biotin switch assay, the S-nitrosation of some
      nuclear candidates of Arabidopsis is verified. Proteins usually contain several
      cysteine residues which each might involve in structure of protein active sites.
      So, an important question is: which cysteine residue is the target of S
      nitrosation and does it belong to an active site? Here, using the approach of
      substitution of cysteines by serines on recombinant proteins, the NO-sensitive
      cysteine residue of an Arabidopsis nuclear protein is identified. The next step
      could be to investigate the effect of S-nitrosation on protein activity/function
      and further to test the role of target cysteines and S-nitrosation of them in
      protein activity/function.

PMID- 29600461
TI  - Detection of S-Nitrosated Nuclear Proteins in Pathogen-Treated Arabidopsis Cell
      Cultures Using Biotin Switch Technique.
AB  - Nitric oxide (NO) is an important signaling molecule involved in various plant
      physiological processes. The main effect of NO arises from its reaction with
      proteins. S-Nitrosation is the most studied NO-mediated protein posttranslational
      modification in plants. Via S-nitrosation, NO derivatives react with thiol groups
      (SHs) of protein cysteine residues and produce nitrosothiol groups (SNOs). From
      the time of discovering the biological function of NO in plants, an interesting
      case of study has been the detection of the endogenous S-nitrosated proteins in
      different plants, tissues, organelles, and various conditions. Maps of S
      nitrosated proteins provide hints for deeper studies on the function of this
      modification in specific proteins, biochemical pathways, and physiological
      processes. Many functions of NO have been found to be related to plant defense;
      on the other hand the involvement of nuclear proteins in regulation of plant
      defense reactions is well studied. Here, an approach is described in which the
      Arabidopsis cell cultures first are treated with P. syringae, afterward their
      bioactive nuclear proteins are extracted, then the nuclear proteins are subjected
      to biotin switch assay in which S-nitrosated proteins are specifically converted
      to S-biotinylated proteins. The biotin switch technique (BST) which was
      introduced by Jaffrey et al. (Nat Cell Biol 3:193-197, 2001) solves the
      instability issue of SNOs. Additionally, it provides detection and purification
      of biotinylated proteins by anti-biotin antibody and affinity chromatography,
      respectively.

PMID- 29600462
TI  - Nitric Oxide Analyzer Quantification of Plant S-Nitrosothiols.
AB  - Nitric oxide (NO) is a small diatomic molecule that regulates multiple
      physiological processes in animals, plants, and microorganisms. In animals, it is
      involved in vasodilation and neurotransmission and is present in exhaled breath.
      In plants, it regulates both plant immune function and numerous developmental
      programs. The high reactivity and short half-life of NO and cross-reactivity of
      its various derivatives make its quantification difficult. Different methods
      based on calorimetric, fluorometric, and chemiluminescent detection of NO and its
      derivatives are available, but all of them have significant limitations. Here we
      describe a method for the chemiluminescence-based quantification of NO using
      ozone-chemiluminescence technology in plants. This approach provides a sensitive,
      robust, and flexible approach for determining the levels of NO and its signaling
      products, protein S-nitrosothiols.

PMID- 29600463
TI  - Nitro-Fatty Acid Detection in Plants by High-Pressure Liquid Chromatography
      Coupled to Triple Quadrupole Mass Spectrometry.
AB  - In the last few years, the role of nitric oxide (NO) and NO-related molecules has
      attracted attention in the field of plant systems. In this sense, the ability of
      NO to mediate several posttranslational modifications (NO-PTM) in different
      biomolecules, such as protein tyrosine nitration or S-nitrosylation, has shown
      the involvement of these reactive nitrogen species in a wide range of functions
      in plant physiology such as the antioxidant response or the involvement in
      processes such as germination, growth, development, or senescence. However,
      growing interest has focused on the interaction of these NO-derived molecules
      with unsaturated fatty acids, yielding nitro-fatty acids (NO2-FAs). It has
      recently been shown that these molecules are involved in key signaling pathways
      in animal systems through the implementation of antioxidant and anti-inflammatory
      responses. Nevertheless, this interaction has been poorly studied in plant
      systems. Very recently, the endogenous presence of NO2-FAs in the model plant
      Arabidopsis thaliana has been demonstrated as well as the significant involvement
      of nitro-linolenic acid (NO2-Ln) in the defence response against several abiotic
      and oxidative stress conditions. In this respect, the detection of NO2-FAs in
      plant systems can be a useful tool to determine the importance of these molecules
      in the regulation of different biochemical pathways. Using high-pressure liquid
      chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS), the
      methods described in this chapter enable the determination of the NO2-FA content
      in a pM range as well as the characterization of these nitrated derivatives of
      unsaturated fatty acids in plant tissues.

PMID- 29600464
TI  - Bioinformatic Prediction of S-Nitrosylation Sites in Large Protein Datasets.
AB  - S-nitrosylation is an essential and reversible posttranslational modification of
      proteins involved in numerous biological processes. The experimental
      determination of S-nitrosylation sites is laborious and time-consuming.
      Therefore, the use of computational prediction tools of this modification
      represents a convenient first approach to generate useful information for
      subsequent experimental verification. Here we describe an in silico analysis
      pipeline to integrate the use of several bionformatic tools while dealing with
      big query protein sets.

PMID- 29600465
TI  - Biotin Switch Processing and Mass Spectrometry Analysis of S-Nitrosated
      Thioredoxin and Its Transnitrosation Targets.
AB  - S-Nitrosation is a key posttranslational modification in regulating proteins in
      both normal physiology and diverse human diseases. To identify novel therapies
      for human diseases linked to oxidative and nitrosative stress, understanding how
      cells control S-nitrosation specificity could be critical. Among the enzymes
      known to control S-nitrosation of proteins, thioredoxin 1 (Trx1), a conserved
      disulfide reductase, transnitrosates and denitrosates distinct sets of target
      proteins. To recognize the function of Trx1 in both normal and dysfunctional
      cells, S-nitrosation targets of Trx1 in different cells need to be identified.
      However, S-nitrosation is usually too labile to be detected directly by mass
      spectrometry (MS). Here we present two optimized MS techniques to identify S
      nitrosated Trx1 and its transnitrosation targets, using both direct and indirect
      MS methods.

PMID- 29600466
TI  - Immunodetection of S-Nitrosoglutathione Reductase Protein in Plant Samples.
AB  - S-nitrosation, the attachment of a nitroso group to cysteine thiols, has been
      recognized as an important posttranslational modification of proteins by nitric
      oxide and related reactive nitrogen species. Mechanisms and significance of S
      nitrosation in the regulation of the structure and activity of proteins have been
      extensively studied in animal and plant systems. In plants, protein S-nitrosation
      is involved in signaling pathways of plant hormones and regulators during plant
      growth and development and in responses to abiotic and biotic stress stimuli. S
      nitrosoglutathione reductase (GSNOR) has been identified as a key enzyme
      controlling the intracellular level of S-nitrosothiols. GSNOR irreversibly
      degrades S-nitrosoglutathione (GSNO), the major low molecular weight S
      nitrosothiol involved in the formation of protein S-nitrosothiols through
      transnitrosylation. GSNOR level and activity in plant cells are modulated during
      plant development and in response to external stimuli such as pathogen infection.
      In this chapter, we give a detailed description of the immunochemical detection
      of the GSNOR protein in plant samples.

PMID- 29600467
TI  - Thioredoxin-Dependent Decomposition of Protein S-Nitrosothiols.
AB  - The addition of nitric oxide to cysteine moieties of proteins results in the
      formation of S-nitrosothiols (SNO) that have emerged as important
      posttranslational signaling cues in a wide variety of eukaryotic processes. While
      formation of protein-SNO is largely nonenzymatic, the conserved family of
      Thioredoxin (TRX) enzymes are capable of selectively reducing protein-SNO.
      Consequently, TRX enzymes are thought to provide reversibility and specificity to
      protein-SNO signaling networks. Here, we describe an in vitro methodology based
      on enzymatic oxidoreductase and biotin-switch techniques, allowing for the
      detection of protein-SNO targets of TRX enzymes. We show that this methodology
      identifies both global and specific protein-SNO targets of TRX in plant cell
      extracts.

PMID- 29600468
TI  - Multivariate analysis for source identification of pollution in sediment of
      Linggi River, Malaysia.
AB  - Rapid socioeconomic development in the Linggi River Basin has contributed to the
      significant increase of pollution discharge into the Linggi River and its
      adjacent coastal areas. The toxic element contents and distributions in the
      sediment samples collected along the Linggi River were determined using neutron
      activation analysis (NAA) and inductively coupled plasma-mass spectrometry (ICP
      MS) techniques. The measured mean concentration of As, Cd, Pb, Sb, U, Th and Zn
      is relatively higher compared to the continental crust value of the respective
      element. Most of the elements (As, Cr, Fe, Pb, Sb and Zn) exceeded the freshwater
      sediment quality guideline-threshold effect concentration (FSQG-TEC) value.
      Downstream stations of the Linggi River showed that As concentrations in sediment
      exceeded the freshwater sediment quality guideline-probable effect concentration
      (FSQG-PEC) value. This indicates that the concentration of As will give an
      adverse effect to the growth of sediment-dwelling organisms. Generally, the
      Linggi River sediment can be categorised as unpolluted to strongly polluted and
      unpolluted to strongly to extremely polluted. The correlation matrix of metal
      metal relationship, principle component analysis (PCA) and cluster analysis (CA)
      indicates that the pollution sources of Cu, Ni, Zn, Cd and Pb in sediments of the
      Linggi River originated from the industry of electronics and electroplating.
      Elements of As, Cr, Sb and Fe mainly originated from motor-vehicle workshops and
      metal work, whilst U and Th originated from natural processes such as terrestrial
      runoff and land erosion.

PMID- 29600469
TI  - Correction to: The use of Data Envelopment Analysis (DEA) in healthcare with a
      focus on hospitals.
AB  - The original version of this article unfortunately contained errors. The first
      column of Tables 5 and 6 in the Appendix section should contain the year of
      publication instead of the reference number in brackets. The reference citations
      were then placed in the second column.

PMID- 29600470
TI  - Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of
      Bevacizumab, Ranibizumab and Aflibercept through Human Sclera.
AB  - PURPOSE: Permeation studies, with near infrared (NIR) light and anti-aggregation
      antibody formulation, were used to investigate the in vitro permeation of
      bevacizumab, ranibizumab and aflibercept through human sclera. METHODS: A
      vertical, spherical Franz cell diffusion apparatus was used for this scleral
      tissue permeation model. A photokinetic ocular drug delivery (PODD) testing
      device accommodated the placement of NIR LEDs above the donor chambers. An
      adjustable LED driver/square wave generator provided electrical energy with a
      variable pulse rate and pulse width modulation (duty cycle). RESULTS: Exposure to
      non-thermal NIR light had no effect on mAbs with regard to monomer concentration
      or antibody binding potential, as determined by SE-HPLC and ELISA. The optimal
      LED wavelength was found to be 950 nm. Duty cycle power of 5% vs 20% showed no
      difference in permeation. When compared to controls, the combination of non
      aggregating antibody formulation and NIR illumination provided an average
      transscleral drug flux enhancement factor of 3X. CONCLUSION: Narrow wavelength
      incoherent (non-laser) light from an NIR LED source is not harmful to mAbs and
      can be used to enhance drug permeation through scleral tissue. The topical
      formulation, combined with pulsed NIR light irradiation, significantly improved
      scleral permeation of three anti-VEGF antibody drugs.

PMID- 29600471
TI  - Migration Background Influences Consumption Patterns Based on Dietary
      Recommendations of Food Bank Users in Germany.
AB  - People with low income tend to eat less balanced than people with higher income.
      This seems to be particularly the case for people with migration background. This
      cross-sectional study examined the relation of consumption patterns of 597 food
      bank users with different migration background in Germany. Questionnaires were
      distributed assessing sociodemographic information and consumption patterns.
      Analyses were conducted using binary logistic regressions. Models were controlled
      for age, gender, type of household and education. The group of German food bank
      users consumed fewer fruits and vegetables and less fish compared to all other
      groups with migration background (former USSR, Balkan region, Middle East). A
      significant predictor for fruit and vegetable consumption was migration status.
      Participants from the former USSR consumed less often SSBs compared to the other
      groups. Dietary recommendations for low income populations should take into
      consideration other aspects besides income such as migration status.

PMID- 29600472
TI  - Maternal consumption of coffee and tea during pregnancy and risk of childhood
      ALL: a pooled analysis from the childhood Leukemia International Consortium.
AB  - PURPOSE: The early onset of childhood acute lymphoblastic leukemia (ALL) suggests
      that critical exposures occurring during pregnancy may increase risk. We
      investigated the effects of maternal coffee and tea consumption during pregnancy
      on ALL risk by pooling data from eight case-control studies participating in the
      Childhood Leukemia International Consortium. METHOD: Data on maternal coffee
      intake were available for 2,552 cases and 4,876 controls, and data on tea intake
      were available for 2,982 cases and 5,367 controls. Coffee and tea intake was
      categorized into 0, > 0-1, > 1-2, and > 2 cups/day, and covariates were combined
      and harmonized. Data on genetic variants in NAT2, CYP1A1, and NQO1 were also
      available in a subset. Pooled odds ratios (ORs) and 95% confidence intervals
      (CIs) were estimated using unconditional logistic regression, and linear trends
      across categories were assessed. RESULTS: No association was seen with 'any'
      maternal coffee consumption during pregnancy, but there was evidence of a
      positive exposure-response; the pooled OR for > 2 cups/day versus none was 1.27
      (95% CI 1.09-1.43), p trend = 0.005. No associations were observed with tea
      consumption. No interactions were seen between coffee or tea intake and age,
      maternal smoking or genotype, and there was little or no evidence that
      associations with coffee or tea differed among cases with and without chromosomal
      translocations. CONCLUSIONS: Despite some limitations, our findings suggest that
      high coffee intake during pregnancy may increase risk of childhood ALL. Thus,
      current advice to limit caffeine intake during pregnancy to reduce risk of
      preterm birth may have additional benefits.

PMID- 29600473
TI  - Psychosocial Stress and Preterm Birth: The Impact of Parity and Race.
AB  - Objectives Studies examining risk factors for preterm birth (PTB) such as
      psychosocial stress are often focused on women with a history of PTB; however,
      most preterm babies are born to women with no history of preterm birth. Our
      objective was to determine if the relationship between psychosocial stress and
      PTB is altered by parity. Non-Hispanic black (NHB) women have increased
      psychosocial stress and PTB; therefore, we further aimed to determine if race
      alters the relationship between psychosocial stress, parity, and PTB. Methods We
      performed a secondary analysis of the Healthy Pregnancy, Healthy Baby Study
      comparing pregnant women who were primiparous (first pregnancy), multiparous with
      history of preterm birth, or multiparous with history of term birth. Perceived
      stress, perceived racism, interpersonal support, John Henryism and self-efficacy
      were measured using validated instruments. Logistic regression was used to model
      the effect of psychosocial stress on PTB stratified by parity and race. Results
      The analysis entire cohort included 1606 subjects, 426 were primiparous, 268 had
      a history of presterm birth, and 912 had a history of term birth. In women with a
      history of term birth, higher self-efficacy was associated with lower odds of
      spontaneous PTB, and this association was amplified in NHB women. In women with a
      history of spontaneous PTB, John Henryism Active Coping was associated with lower
      odds of spontaneous PTB in the index pregnancy. Conclusions for Practice The
      relationship between psychosocial stress and PTB may be mediated by parity and
      race.

PMID- 29600474
TI  - Combined percutaneous radiofrequency ablation and ethanol injection versus
      hepatic resection for 2.1-5.0 cm solitary hepatocellular carcinoma: a
      retrospective comparative multicentre study.
AB  - OBJECTIVES: To compare combined percutaneous radiofrequency ablation and ethanol
      injection (RFA-PEI) with hepatic resection (HR) in the treatment of resectable
      solitary hepatocellular carcinoma (HCC) with 2.1-5.0 cm diameter. METHODS: From
      June 2009 to December 2015, 271 patients whom underwent RFA-PEI (n = 141) or HR
      (n = 130) in three centres were enrolled. The overall survival (OS) and
      recurrence-free survival (RFS) between groups were compared with Kaplan-Meier
      method and log-rank tests. Complications, hospital stay and cost were assessed.
      RESULTS: The OS rates at 1, 3 and 5 years were 93.5%, 72.7%, 58.6% in RFA-PEI
      group and 82.3%, 57.5%, 51.8% in HR group (p = 0.021). The corresponding 1-, 3-
      and 5-year RFS rates were 65.8%, 41.3%, 34.3% in RFA-PEI group and 50.5%, 33.8%,
      28.4% in HR group (p = 0.038). For patients with 2.1-3.0 cm tumours, the 1-, 3-
      and 5-year OS after RFA-PEI and HR were 98.0%, 82.3%, 74.2% and 89.4%, 65.1%,
      61.9%, respectively (p = 0.024). The corresponding RFS were 79.6%, 54.7%, 45.1%
      in RFA-PEI group, and 57.6%, 43.9%, 31.7% in HR group, respectively (p = 0.020).
      RFA-PEI was superior to HR in major complication rates, length of hospital stay
      and cost (all p < 0.001). CONCLUSION: RFA-PEI had a survival benefit over HR in
      the treatment of solitary HCCs, especially for those with 2.1-3.0 cm in diameter.
      KEY POINTS: * RFA-PEI provided superior survival to HR in solitary HCC with 2.1
      5.0 cm in diameter. * RFA-PEI is superior to HR in complications, length of
      hospital stay and cost. * RFA-PEI might be an alternative treatment for solitary
      HCC within 5.0 cm in diameter.

PMID- 29600475
TI  - Structured reporting adds clinical value in primary CT staging of diffuse large B
      cell lymphoma.
AB  - OBJECTIVES: To evaluate whether template-based structured reports (SRs) add
      clinical value to primary CT staging in patients with diffuse large B-cell
      lymphoma (DLBCL) compared to free-text reports (FTRs). METHODS: In this two
      centre study SRs and FTRs were acquired for 16 CT examinations. Thirty-two
      reports were independently scored by four haematologists using a questionnaire
      addressing completeness of information, structure, guidance for patient
      management and overall quality. The questionnaire included yes-no, 10-point
      Likert scale and 5-point scale questions. Altogether 128 completed questionnaires
      were evaluated. Non-parametric Wilcoxon signed-rank test and McNemar's test were
      used for statistical analysis. RESULTS: SRs contained information on affected
      organs more often than FTRs (95 % vs. 66 %). More SRs commented on extranodal
      involvement (91 % vs. 62 %). Sufficient information for Ann-Arbor classification
      was included in more SRs (89 % vs. 64 %). Information extraction was quicker from
      SRs (median rating on 10-point Likert scale=9 vs. 6; 7-10 vs. 4-8 interquartile
      range). SRs had better comprehensibility (9 vs. 7; 8-10 vs. 5-8). Contribution of
      SRs to clinical decision-making was higher (9 vs. 6; 6-10 vs. 3-8). SRs were of
      higher quality (p < 0.001). All haematologists preferred SRs over FTRs.
      CONCLUSIONS: Structured reporting of CT examinations for primary staging in
      patients with DLBCL adds clinical value compared to FTRs by increasing
      completeness of reports, facilitating information extraction and improving
      patient management. KEY POINTS: * Structured reporting in CT helps clinicians to
      assess patients with lymphoma. * This two-centre study showed that structured
      reporting improves information content and extraction. * Patient management may
      be improved by structured reporting. * Clinicians preferred structured reports
      over free-text reports.

PMID- 29600476
TI  - Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding
      with chronic portal vein occlusion after splenectomy.
AB  - OBJECTIVES: The purpose of this study was to introduce a modified transjugular
      intrahepatic portosystemic shunt (TIPS), a percutaneous transhepatic intrahepatic
      portosystemic shunt (PTIPS), and to evaluate its feasibility and efficacy in
      patients with variceal bleeding with chronic portal vein occlusion (CPVO) after
      splenectomy. METHODS: Twenty-four cirrhotic patients with CPVO after splenectomy
      who received PTIPS between 2010 and 2015 were included in this retrospective
      study. The indication was elective control of variceal bleeding. Success rates,
      effectiveness and complications were evaluated, with comparison of the pre- and
      post-portosystemic pressure gradient (PPG). Patients' clinical outcomes and shunt
      patency were followed periodically. RESULTS: PTIPS was successfully placed in 22
      patients (91.7%) and failed in two. The mean PPG fell from 22.0 +/- 4.9 mmHg to
      10.6 +/- 1.6 mmHg after successful PTIPS (p < 0.05). No fatal procedural
      complications occurred. During the median follow-up of 29 months, shunt
      dysfunction occurred in five cases and hepatic encephalopathy in four cases.
      Three patients died because of rebleeding, hepatic failure and pulmonary disease,
      respectively. The other patients remained asymptomatic and the shunts patent.
      CONCLUSIONS: We conclude that PTIPS, as a modified TIPS procedure with a high
      success rate, is safe and effective for variceal bleeding with CPVO after
      splenectomy. KEY POINTS: * Portal vein occlusion used to be contraindication to
      transjugular intrahepatic portosystemic shunt. * Portal vein thrombosis is common
      in patients with previous splenectomy. * We developed a new method, percutaneous
      transhepatic intrahepatic portosystemic shunt (PTIPS). * PTIPS is feasible in
      patients with portal vein thrombosis and splenectomy. * PTIPS is effective and
      safe for these kind of complicated portal hypertension.

PMID- 29600477
TI  - In vivo study of enhanced chemotherapy combined with ultrasound image-guided
      focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse
      model.
AB  - OBJECTIVES: This study was designed to investigate whether focused ultrasound
      (FUS) treatment with a higher mechanical index (MI) can enhance the effects of
      combined chemotherapy more than with a lower MI, and to evaluate the feasibility
      of the chemotherapy combined with FUS at a higher MI as an alternative treatment
      protocol. METHODS: Mice in the first study were divided into six groups: control,
      chemotherapy only (GEM), two groups treated with FUS only at two different MIs,
      and two groups treated with chemotherapy and FUS (GEM + FUS). Mice were treated
      with a single-session treatment; one session consisted of three weekly treatments
      and 1 week of follow-up monitoring. In the second study, mice were assigned to
      two groups (GEM, GEM + FUS) and treated with four treatment sessions. RESULTS: In
      the single-session treatment, tumor growth was most effectively suppressed in GEM
      + FUS group with a higher MI. Tumor growth rate was significantly lower in GEM +
      FUS group than in GEM group for multiple-session treatment. Specifically, three
      of ten mice in GEM + FUS group showed complete remission. CONCLUSIONS: This study
      demonstrated that FUS at a higher MI can enhance chemotherapy outcomes more than
      at a lower MI and demonstrated the potential of FUS in combination with
      chemotherapy as a new cancer treatment protocol. KEY POINTS: * Combined treatment
      of chemotherapy and focused ultrasound can effectively suppress tumor growth. *
      For the focused ultrasound treatment conditions used in this study, focused
      ultrasound with relatively higher mechanical index shows more enhanced
      therapeutic outcomes than with the lower mechanical index. * Combination therapy
      shows the possibility as a new cancer treatment protocol.

PMID- 29600478
TI  - Abnormal brain structure as a potential biomarker for venous erectile
      dysfunction: evidence from multimodal MRI and machine learning.
AB  - OBJECTIVES: To investigate the cerebral structural changes related to venous
      erectile dysfunction (VED) and the relationship of these changes to clinical
      symptoms and disorder duration and distinguish patients with VED from healthy
      controls using a machine learning classification. METHODS: 45 VED patients and 50
      healthy controls were included. Voxel-based morphometry (VBM), tract-based
      spatial statistics (TBSS) and correlation analyses of VED patients and clinical
      variables were performed. The machine learning classification method was adopted
      to confirm its effectiveness in distinguishing VED patients from healthy
      controls. RESULTS: Compared to healthy control subjects, VED patients showed
      significantly decreased cortical volumes in the left postcentral gyrus and
      precentral gyrus, while only the right middle temporal gyrus showed a significant
      increase in cortical volume. Increased axial diffusivity (AD), radial diffusivity
      (RD) and mean diffusivity (MD) values were observed in widespread brain regions.
      Certain regions of these alterations related to VED patients showed significant
      correlations with clinical symptoms and disorder durations. Machine learning
      analyses discriminated patients from controls with overall accuracy 96.7%,
      sensitivity 93.3% and specificity 99.0%. CONCLUSIONS: Cortical volume and white
      matter (WM) microstructural changes were observed in VED patients, and showed
      significant correlations with clinical symptoms and dysfunction durations.
      Various DTI-derived indices of some brain regions could be regarded as reliable
      discriminating features between VED patients and healthy control subjects, as
      shown by machine learning analyses. KEY POINTS: * Multimodal magnetic resonance
      imaging helps clinicians to assess patients with VED. * VED patients show
      cerebral structural alterations related to their clinical symptoms. * Machine
      learning analyses discriminated VED patients from controls with an excellent
      performance. * Machine learning classification provided a preliminary
      demonstration of DTI's clinical use.

PMID- 29600479
TI  - CT analysis of the aorta in giant-cell arteritis: a case-control study.
AB  - OBJECTIVES: Giant cell arteritis (GCA) is a large-vessel vasculitis whose
      diagnosis is confirmed by temporal artery biopsy. However, involvement of large
      vessels, especially the aorta, can be shown by imaging, which plays an increasing
      role in GCA diagnosis. The threshold above which aortic wall thickening, as
      measured by computed tomography (CT), is considered pathological is
      controversial, with values ranging from 2 to 3 mm. This study assessed aortic
      morphology by CT scan and its diagnostic value in GCA. METHODS: Altogether, 174
      patients were included (64 with GCA, 43 with polymyalgia rheumatica and 67
      controls). All patients had a CT scan at diagnosis or at inclusion for controls.
      Aortic wall thickness, aortic diameter and scores for atheroma were measured.
      Assessor was blinded to each patient's group. RESULTS: Aortic diameters and
      atheroma scores were similar between groups. Aortic wall thickness was greater in
      the GCA group, even after the exclusion of GCA patients with aortic wall
      thickness >=3 mm. The receiver operating characteristic (ROC) curve showed that a
      wall thickness of 2.2 mm was the optimal threshold to diagnose GCA (sensitivity,
      67%; specificity, 98%). CONCLUSIONS: Measuring aortic wall thickness by CT scan
      is effective to diagnose GCA. The optimal threshold to regard aortic wall
      thickening as pathological was >=2.2 mm. KEY POINTS: * Imaging, including CT
      scan, plays an increasing role in GCA diagnosis * CT measurement of aortic wall
      thickness is useful to diagnose GCA * A 2.2-mm threshold allows the diagnosis of
      thickened aortic wall in GCA.

PMID- 29600481
TI  - Similarities between the irrelevant sound effect and the suffix effect.
AB  - Although articulatory suppression abolishes the effect of irrelevant sound (ISE)
      on serial recall when sequences are presented visually, the effect persists with
      auditory presentation of list items. Two experiments were designed to test the
      claim that, when articulation is suppressed, the effect of irrelevant sound on
      the retention of auditory lists resembles a suffix effect. A suffix is a spoken
      word that immediately follows the final item in a list. Even though participants
      are told to ignore it, the suffix impairs serial recall of auditory lists. In
      Experiment 1, the irrelevant sound consisted of instrumental music. The music
      generated a significant ISE that was abolished by articulatory suppression. It
      therefore appears that, when articulation is suppressed, irrelevant sound must
      contain speech for it to have any effect on recall. This is consistent with what
      is known about the suffix effect. In Experiment 2, the effect of irrelevant sound
      under articulatory suppression was greater when the irrelevant sound was spoken
      by the same voice that presented the list items. This outcome is again consistent
      with the known characteristics of the suffix effect. It therefore appears that,
      when rehearsal is suppressed, irrelevant sound disrupts the acoustic-perceptual
      encoding of auditorily presented list items. There is no evidence that the
      persistence of the ISE under suppression is a result of interference to the
      representation of list items in a postcategorical phonological store.

PMID- 29600480
TI  - Fragmented particles containing octreotide acetate prepared by spray drying
      technique for dry powder inhalation.
AB  - Dry powder inhalers (DPIs) have been proposed as an alternative administration
      route for protein and peptide drugs. However, DPI particles are easy to aggregate
      due to the strong interactions between the particles, leading to poor
      aerosolization performance. In this study, fragmented particles containing
      octreotide acetate (OA) were prepared by spray drying technique for dry powder
      inhalation, which were expected to decrease the particle-particle interaction by
      reducing the contact sites. Mannitol and ammonium carbonate were used as protein
      stabilizer and fragment-forming agent, respectively. The obtained fragmented
      particles presented larger particle size, lower density, better dispersibility,
      and well in vitro aerodynamic behavior (emitted dose > 97%, fine particle
      fraction ~ 40%). The circular dichroism spectrum results indicated that OA
      maintained the stability throughout the spray drying process. The relative
      bioavailability of dry powder inhalation (DPI) compared with subcutaneous
      injection of commercial product was up to 88.0%, demonstrating the feasibility of
      DPI for OA delivery. These results confirmed that the proposed fragmented
      particles had great potential for pulmonary delivery of protein and peptide drugs
      in a painless, rapid, and convenient manner.

PMID- 29600482
TI  - Pectoral nerves I block is associated with a significant motor blockade with no
      dermatomal sensory changes: a prospective volunteer randomized-controlled double
      blind study.
AB  - PURPOSE: The pectoral nerves (PECS) I block, first described in 2011 for surgery
      involving the pectoralis muscle, has principally been used for breast cancer
      surgery. No formal evaluation of its differential motor- and sensory-blocking
      abilities has been reported. We hypothesize that the PECS I block will produce a
      motor block of the pectoralis muscles with diminished upper limb adduction
      strength as measured with a handheld dynamometer. METHODS: We conducted a PECS I
      block in a randomized placebo-controlled trial in six healthy subjects who
      received 0.4 mL.kg-1 of 0.9% saline (placebo) on one side and bupivacaine (0.25%
      with 1:400 000 epinephrine) on the other. We measured both upper limb adduction
      strength with a dynamometer and sensory skin levels over the thorax. RESULTS: The
      mean (standard deviation [SD]) adductor strength evaluated before the block was
      119.4 (20.7) Newtons (N). After the PECS I block with bupivacaine, the mean (SD)
      strength of 54.2 (16.3) N was compared with 116.0 (30.4) N in the placebo group
      (difference in means 61.8 N; 95% confidence interval [CI], 27.8 to 95.8 N; P =
      0.005), showing a 54.6% (95% CI, 43.6 to 65.6%) reduction in adductor strength.
      There was no difference in dermatomal skin sensory testing between the placebo
      and bupivacaine sides. CONCLUSIONS: This study shows that a PECS I block produces
      motor blockade as shown by reduced upper limb adductor strength without any
      overlying dermatomal sensory loss. TRIAL REGISTRATION: www.clinicaltrials.gov
      (NCT03040167) 2 February 2017.

PMID- 29600483
TI  - Updated guide for the management of malignant hyperthermia.
AB  - PURPOSE: This continuing professional development module aims to prepare
      anesthesiologists for the timely recognition and management of a malignant
      hyperthermia (MH) reaction, which is crucial for averting its life-threatening
      complications and ultimately for the patient's survival. PRINCIPAL FINDINGS:
      Malignant hyperthermia is a genetic disorder of skeletal muscle cells affecting
      myoplasmic calcium homeostasis. It can present with nonspecific signs of a
      hypermetabolic reaction, which can be fatal if treatment, including
      administration of dantrolene sodium, is not implemented promptly. Rapid
      evaluation and rejection of alternative diagnoses can lead to a prompt diagnosis
      and treatment and therefore will significantly reduce the complications,
      including renal failure, cardiac dysfunction, disseminated intravascular
      coagulation, and death. After the reaction, patients should be observed for a
      minimum of 24 hr because of the possibility of recrudescence. As it is a genetic
      condition, survivors and their family members should be referred to a specialized
      MH centre for further testing and counselling. CONCLUSIONS: The risk of dying
      from MH has increased over the past few years. A knowledgeable anesthesiologist
      who is diligent and attentive can recognize signs of an impending MH reaction and
      treat promptly to avoid complications of this deadly condition.

PMID- 29600484
TI  - Morphometrics of the Southern Green Stink Bug [Nezara viridula (L.) (Hemiptera:
      Pentatomidae)] Stylet Bundle.
AB  - The southern green stink bug, Nezara viridula (L.) (Hemiptera: Pentatomidae), is
      a cosmopolitan pest of high-value cash crops, including cotton (Gossypium
      hirsutum L.; Malvales: Malvaceae). The pest can ingest and transmit disease
      causing bacterial and fungal pathogens of cotton. We hypothesized that the size
      of the food canal may contribute to selective transmission, as observed in
      previous reports. The objective of this study was to examine food canal size and
      other morphometric parameters of the southern green stink bug stylet bundle at
      two locations (labium and head) to improve our understanding of factors that may
      contribute to pathogen transmission. For the food canal, females possessed
      significantly larger canals than males, major axes were significantly longer than
      minor axes, and canal sizes were numerically higher at the labium compared with
      the head. For salivary canal, mean axes lengths were similar between sexes and
      the head and labium. For both food and salivary canals, axes lengths were longer
      and area was larger at the labium compared with the head. These findings indicate
      the presence of a "funnel effect" with canals becoming narrower proximally. Sex
      and location significantly affected the size of the intact stylet bundle. Results
      indicate the food canal size was not a factor affecting previously observed
      selective passive transmission. Major and minor axes measurements, coupled with
      morphological observations of canal shapes and observed "funnel effect" in the
      food and salivary canals, improve our understanding of the hemipteran stylet
      bundle and its relationship with the insect's internal morphology.

PMID- 29600485
TI  - Diffuse fibrosis is common in the left, but not in the right ventricle in
      patients with transposition of the great arteries late after atrial switch
      operation.
AB  - In adult patients with transposition of the great arteries (TGA) late after
      atrial switch operation (AtSO), each of the ventricles is faced with a profoundly
      different pressure regimen from the one they are meant to support in normal
      conditions. The extent of diffuse fibrosis of the right ventricle (RV) and left
      ventricle (LV) in these patients remains incompletely investigated. Aim of this
      study was to quantify the degree of fibrosis of the unloaded LV and of the
      overloaded RV by determining the myocardial extracellular volume (ECV) with non
      invasive techniques as T1 mapping. We determined ECV by cardiac magnetic
      resonance (CMR) in 10 patients (36.8 +/- 5.3 years old) with TGA late after AtSO,
      without relevant pulmonary stenosis, by acquiring T1-maps of the myocardium
      before and 10 min after injection of Gadolinium-based contrast agent. ECV of the
      inferior wall (36% (33-41%)) and of the lateral wall (37% (35-39%)) of the LV was
      significantly increased compared to the ECV of the RV (27% (25-29%)), in both
      comparisons P < 0.0001. Long-time LV unloading following atrial switch procedures
      leads to severe myocardial fibrosis of the subpulmonary LV. T1 mapping CMR might
      be useful for selection of patients with atrial switch operation, in whom
      reestablishment of the LV as a systemic ventricle by staged arterial switch
      operation is planned. However larger studies and newer higher resolution methods
      for T1-mapping are needed to determine the role of ECV in the decision of a
      surgical intervention in this kind of population.

PMID- 29600488
TI  - Origin and location of new Arctic islands and straits due to glacial recession.
AB  - A total of 34 new islands (each 0.5 km2 or above) have appeared due to recession
      of Arctic glaciers under climate warming since the 1960s. Analysis of maps and
      satellite images of the Arctic coasts has been a basic method of recognizing
      these islands. Their origin is the final stage of a process which began in the
      twentieth century. They appear only on the coasts where bedrock elevations above
      sea level are surrounded by depressions below this level, filled (at least from
      the landside) with glaciers. Their recession leads to flooding of the depressions
      by sea water, thus creating straits which separate the new islands from the
      mainland. Hence, such new islands appear only in Greenland and the European
      Arctic. Their ecosystems accommodate to new environmental conditions. In the near
      future, this process will be intensified in a situation of further warming.

PMID- 29600486
TI  - Influence of corticosteroid therapy on IL-18 and nitric oxide production during
      Behcet's disease.
AB  - BACKGROUND AND AIMS: Behcet's disease (BD) is a chronic multisystemic
      inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines
      seem to be involved in its pathogenesis. Our current study aims to evaluate
      interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of
      different clinical manifestations of BD as well as to investigate the
      corticosteroid therapy effect on this production in Algerian patients. METHODS:
      For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-gamma (IFN
      gamma) levels using ELISA and NO production by the Griess' method in naive-active
      and corticosteroid-treated BD patients with different clinical manifestations.
      Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in
      these groups of patients. RESULTS AND DISCUSSION: Our results indicate that IL-18
      and nitrite levels were higher in naive-active BD patients. Interestingly, this
      high production differed according to the clinical manifestations and was
      associated with an increased risk of mucocutaneous and vascular involvement.
      Concerning corticosteroid treated-active BD patients, no difference was observed
      in this production between each clinical subgroup. However, IFN-gamma levels
      increased in all categories of active patients. Interestingly, corticosteroid
      therapy reduced significantly these inflammatory mediators regardless of the
      clinical manifestations studied. In addition, the CD40/CD40L expression differed
      according to the clinical presentations. CONCLUSION: Collectively, our results
      suggest that concomitant high production of IL-18 and NO in naive-active BD
      patients is related to an increased risk of mucocutaneous lesions and vascular
      involvement. Moreover, the relationship between these two inflammatory markers
      could constitute a predictable tool of BD clinical presentations and an early
      factor of therapy efficiency.

PMID- 29600487
TI  - Lead poisoning and other human-related factors cause significant mortality in
      white-tailed eagles.
AB  - The white-tailed eagle (Haliaeetus albicilla) suffered a severe population
      decline due to environmental pollutants in the Baltic Sea area ca. 50 years ago
      but has since been recovering. The main threats for the white-tailed eagle in
      Finland are now often related to human activities. We examined the human impact
      on the white-tailed eagle by determining mortality factors of 123 carcasses
      collected during 2000-2014. Routine necropsy with chemical analyses for lead and
      mercury were done on all carcasses. We found human-related factors accounting for
      60% of the causes of death. The most important of these was lead poisoning (31%
      of all cases) followed by human-related accidents (e.g. electric power lines and
      traffic) (24%). The temporal and regional patterns of occurrence of lead
      poisonings suggested spent lead ammunition as the source. Lead shot was found in
      the gizzards of some lead-poisoned birds. Scavenging behaviour exposes the white
      tailed eagle to lead from spent ammunition.

PMID- 29600489
TI  - Predictive visual search: Role of environmental regularities in the learning of
      context cues.
AB  - Repeatedly searching through invariant spatial arrangements in visual search
      displays leads to the buildup of memory about these displays (contextual-cueing
      effect). In the present study, we investigate (1) whether contextual cueing is
      influenced by global statistical properties of the task and, if so, (2) whether
      these properties increase the overall strength (asymptotic level) or the temporal
      development (speed) of learning. Experiment 1a served as baseline against which
      we tested the effects of increased or decreased proportions of repeated relative
      to nonrepeated displays (Experiments 1b and 1c, respectively), thus manipulating
      the global statistical properties of search environments. Importantly,
      probability variations were achieved by manipulating the number of nonrepeated
      (baseline) displays so as to equate the total number of repeated displays across
      experiments. In Experiment 1d, repeated and nonrepeated displays were presented
      in longer streaks of trials, thus establishing a stable environment of sequences
      of repeated displays. Our results showed that the buildup of contextual cueing
      was expedited in the statistically rich Experiments 1b and 1d, relative to the
      baseline Experiment 1a. Further, contextual cueing was entirely absent when
      repeated displays occurred in the minority of trials (Experiment 1c). Together,
      these findings suggest that contextual cueing is modulated by observers'
      assumptions about the reliability of search environments.

PMID- 29600490
TI  - Development and Psychometric Testing of the Transition Service Provider
      Competency Scale.

PMID- 29600491
TI  - Telepsychiatry: an Innovative Approach to Addressing the Opioid Crisis.
AB  - The opioid epidemic faced by the USA is a complex public health crisis, with
      staggering loss of life and overwhelming social, health, and economic costs.
      Despite the rising need for medication-assisted treatment, individuals struggling
      with opioid use continue to face multiple barriers hindering their access to
      care, particularly in rural areas. Innovative approaches to enhance access to
      treatment are needed. Telepsychiatry has proven to be effective and economical
      across multiple settings and psychiatric diagnoses, including opioid use
      disorder. As the implementation of telepsychiatry continues to expand, this
      method of healthcare delivery offers significant opportunities to overcome
      several barriers to access patients with opioid use disorder face. While
      addressing the opioid crisis will require multifaceted efforts involving multiple
      stakeholders and different approaches, a comprehensive strategy must incorporate
      the adoption of telepsychiatry as an innovative approach to overcoming barriers
      to treatment and enhancing access to care.

PMID- 29600492
TI  - The effects of gene disruption of Kre6-like proteins on the phenotype of beta
      glucan-producing Aureobasidium pullulans.
AB  - Killer toxin resistant 6 (Kre6) and its paralog, suppressor of Kre null 1 (Skn1),
      are thought to be involved in the biosynthesis of cell wall beta-(1 -> 6)-D
      glucan in baker's yeast, Saccharomyces cerevisiae. The Deltakre6Deltaskn1 mutant
      of S. cerevisiae and other fungi shows severe growth defects due to the failure
      to synthesize normal cell walls. In this study, two homologs of Kre6, namely,
      K6LP1 (Kre6-like protein 1) and K6LP2 (Kre6-like protein 2), were identified in
      Aureobasidium pullulans M-2 by draft genome analysis. The Deltak6lp1, Deltak6lp2,
      and Deltak6lp1Deltak6lp2 mutants were generated in order to confirm the functions
      of the Kre6-like proteins in A. pullulans M-2. The cell morphologies of
      Deltak6lp1 and Deltak6lp1Deltak6lp2 appeared to be different from those of wild
      type and Deltak6lp2 in both their yeast and hyphal forms. The productivity of the
      extracellular polysaccharides, mainly composed of beta-(1 -> 3),(1 -> 6)-D-glucan
      (beta-glucan), of the mutants was 5.1-17.3% less than that of wild type, and the
      degree of branching in the extracellular beta-glucan of mutants was 14.5-16.8%
      lower than that of wild type. This study showed that the gene disruption of Kre6
      like proteins affected the cell morphology, the productivity of extracellular
      polysaccharides, and the structure of extracellular beta-glucan, but it did not
      have a definite effect on the cell viability even in Deltak6lp1Deltak6lp2, unlike
      in the Deltakre6Deltaskn1 of S. cerevisiae.

PMID- 29600493
TI  - Drivers of microbial community structure in forest soils.
AB  - Forests are essential biomes for global biogeochemical cycles, and belowground
      microorganisms have a key role in providing relevant ecosystem services. To
      predict the effects of environmental changes on these ecosystem services requires
      a comprehensive understanding of how biotic and abiotic factors drive the
      composition of microbial communities in soil. However, microorganisms are not
      homogeneously distributed in complex environments such as soil, with different
      features affecting microbes at different extent depending on the niche they
      occupy. Indeed, this spatial heterogeneity hampers the extrapolation of microbial
      diversity study results from particular habitats to the ecosystem level, even if
      the resolution of the more recent studies has increased significantly after the
      standardization of high-throughput sequencing techniques. The present work
      intends to give a comprehensive view of the knowledge accumulated until date
      defining the more important drivers determining the structure of forest soil
      microbial communities from fine to continental scales.

PMID- 29600494
TI  - Duox2-induced innate immune responses in the respiratory epithelium and
      intranasal delivery of Duox2 DNA using polymer that mediates immunization.
AB  - Respiratory mucosa especially nasal epithelium is well known as the first-line
      barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are
      detected in in vitro cultured human epithelial cells and in vivo lung. With
      identification of NADPH oxidase (Nox) system of respiratory epithelium, the
      antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox
      isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2
      derived ROS are involved in antiviral innate immune responses but more studies
      are needed to verify the mechanism. In respiratory epithelium, Duox2-derived ROS
      is critical for recognition of virus through families retinoic acid-inducible
      gene-I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) at the
      early stage of antiviral innate immune responses. Various secreted interferons
      (IFNs) play essential roles for antiviral host defense by downstream cell
      signaling, and transcription of IFN-stimulated genes is started to suppress viral
      replication. Type I and type III IFNs are verified more responsible for influenza
      A virus (IAV) infection in respiratory epithelium and Duox2 is required to
      regulate IFN-related immune responses. Transient overexpression of Duox2 using
      cationic polymer polyethylenimine (PEI) induces secretion of type I and type III
      IFNs and significantly attenuated IAV replication in respiratory epithelium.
      Here, we discuss Duox2-mediated antiviral innate immune responses and the role of
      Duox2 as a mucosal vaccine to resist respiratory viral infection.

PMID- 29600495
TI  - A preliminary study of telemedicine for patients with hepatic glycogen storage
      disease and their healthcare providers: from bedside to home site monitoring.
AB  - BACKGROUND: The purpose of this project was to develop a telemedicine platform
      that supports home site monitoring and integrates biochemical, physiological, and
      dietary parameters for individual patients with hepatic glycogen storage disease
      (GSD). METHODS AND RESULTS: The GSD communication platform (GCP) was designed
      with input from software developers, GSD patients, researchers, and healthcare
      providers. In phase 1, prototyping and software design of the GCP has occurred.
      The GCP was composed of a GSD App for patients and a GSD clinical dashboard for
      healthcare providers. In phase 2, the GCP was tested by retrospective patient
      data entry. The following software functionalities were included (a) dietary
      registration and prescription module, (b) emergency protocol module, and (c) data
      import functions for continuous glucose monitor devices and activity wearables.
      In phase 3, the GSD App was implemented in a pilot study of eight patients with
      GSD Ia (n = 3), GSD IIIa (n = 1), and GSD IX (n = 4). Usability was measured by
      the system usability scale (SUS). The mean SUS score was 64/100 [range: 38-93].
      CONCLUSIONS: This report describes the design, development, and validation
      process of a telemedicine platform for patients with hepatic GSD. The GCP can
      facilitate home site monitoring and data exchange between patients with hepatic
      GSD and healthcare providers under varying circumstances. In the future, the GCP
      may support cross-border healthcare, second opinion processes and clinical
      trials, and could possibly also be adapted for other diseases for which a medical
      diet is the cornerstone.

PMID- 29600496
TI  - Allogeneic hematopoietic cell transplantation in Farber disease.
AB  - BACKGROUND: Farber disease (FD) is a rare, lysosomal storage disorder caused by
      deficient acid ceramidase activity. FD has long been considered a fatal disorder
      with death in the first three decades of life resulting either from respiratory
      insufficiency as a consequence of airway involvement or from progressive
      neurodegeneration because of nervous system involvement. Peripheral symptoms
      associated with FD, including inflammatory joint disease, have been described to
      improve relatively rapidly after hematopoietic cell transplantation (HCT). AIMS:
      To evaluate the disease-specific status and limitations in the long-term follow
      up after HCT, investigate genotype/phenotype correlations and the benefit of
      allogeneic HCT in FD patients with nervous system involvement. PATIENTS AND
      METHODS: Transplant- and disease-related information of ten FD patients was
      obtained by using a questionnaire, physicians' letters and additional telephone
      surveys. ASAH1 gene mutations were identified to search for genotype/phenotype
      correlations. RESULTS: After mainly busulfan-based preparative regimens, all
      patients engrafted with one late graft loss. The inflammatory symptoms resolved
      completely in all patients. Abnormal neurologic findings were present pre
      transplant in 4/10 patients, post-transplant in 6/10 patients. Mutational
      analyses revealed new mutations in the ASAH1 gene and a broad diversity of
      phenotypes without a genotype/phenotype correlation. With a median follow-up of
      10.4 years, overall survival was 80% with two transplant-related deaths.
      CONCLUSION: Allogeneic HCT leads to complete and persistent resolution of the
      inflammatory aspects in FD patients. It appears to have no beneficial effect on
      progression of nervous system involvement. New mutations in the acid ceramidase
      gene were identified. A genotype/phenotype correlation could not be established.

PMID- 29600497
TI  - The rendering of human phenotype and rare diseases in ICD-11.
AB  - ICD-11 (International Classification of Diseases, 11th Revision) is the next
      major revision of the ICD by the World Health Organization (WHO). ICD-11 differs
      dramatically from historical versions, as it is based on an underlying semantic
      network of terms and meaning, called the Foundation. To function as a mutually
      exclusive and exhaustive statistical classification, ICD-11 creates derivative
      linearizations from the network that is a monohierarchy with residual categories
      such as Not Elsewhere Classified. ICD-11 also introduces the widespread post
      coordination of terms, which allows for highly expressive representation of
      detailed patient descriptions. Phenotyping features are included in many
      subchapters or the signs and symptoms chapter. Composite phenotype descriptions
      of specific presentations or syndromes can be represented though post
      coordination. Rare diseases are well represented in the Foundation, though not
      all appear in the relatively shallow linearization hierarchies.

PMID- 29600498
TI  - Assessment of water quality monitoring for the optimal sensor placement in lake
      Yahuarcocha using pattern recognition techniques and geographical information
      systems.
AB  - Pollution and the eutrophication process are increasing in lake Yahuarcocha and
      constant water quality monitoring is essential for a better understanding of the
      patterns occurring in this ecosystem. In this study, key sensor locations were
      determined using spatial and temporal analyses combined with geographical
      information systems (GIS) to assess the influence of weather features,
      anthropogenic activities, and other non-point pollution sources. A water quality
      monitoring network was established to obtain data on 14 physicochemical and
      microbiological parameters at each of seven sample sites over a period of 13
      months. A spatial and temporal statistical approach using pattern recognition
      techniques, such as cluster analysis (CA) and discriminant analysis (DA), was
      employed to classify and identify the most important water quality parameters in
      the lake. The original monitoring network was reduced to four optimal sensor
      locations based on a fuzzy overlay of the interpolations of concentration
      variations of the most important parameters.

PMID- 29600499
TI  - Isoflurane anesthesia does not affect spinal cord neurovascular coupling:
      evidence from decerebrated rats.
AB  - Neurological examination remains the primary clinical investigation in patients
      with spinal cord injury. However, neuroimaging methods such as functional
      magnetic resonance imaging (fMRI) are promising tools for following functional
      changes in the course of injury, disease and rehabilitation. However, the
      relationship between neuronal activity and blood flow in the spinal cord on which
      fMRI relies has been largely overlooked. The objective of this study was to
      examine neurovascular coupling in the spinal cord of decerebrated rats during
      electrical stimulation of the sciatic nerve with and without isoflurane
      anesthesia (1.2%). Local field potentials (LFP) and spinal cord blood flow (SCBF)
      were recorded simultaneously in the lumbosacral enlargement. Isoflurane did not
      significantly alter LFP (p = 0.53) and SCBF (p = 0.57) amplitude. Accordingly,
      neurovascular coupling remained comparable with or without isoflurane anesthesia
      (p = 0.39). These results support the use of isoflurane in rodents to investigate
      nociceptive functions of the spinal cord using fMRI.

PMID- 29600500
TI  - Incidence of dental traumatic injuries in children 0-4 years of age: a
      prospective study based on parental reporting.
AB  - AIM: To collect prospective information reported by parents regarding dental
      traumas occurring in children 6 months to 4 years of age, furthermore, to collect
      data on complications from the dental records. METHODS: The staff from the child
      health services distributed a questionnaire at the regular health check-up
      reviews for a number of age groups, i.e., 6, 12, 18, 24, 30, 36, and 42 months of
      age. The parents were to observe and register factors around dental trauma for
      the following 6-month period. The questionnaires (138) were returned,
      irrespective of any trauma having occurred or not. If a child was seeing a
      dentist (emergency visit), the diagnosis of trauma and later complications were
      collected from the dental records. RESULTS: There were 35 of 138 children
      experienced trauma (6-47 months of age). The half-year incidence of trauma in
      children 6 months to 4.0 years of age was between 12 and 48%. A total of 41
      traumatic dental injuries (TDIs) were reported. Of these 24 occurred indoors. The
      most common reason for trauma was falling accidents. In 24 out of the 41 reported
      TDIs the children were not seen by a dentist in connection with the trauma. The
      reason was that the parents thought the trauma did not matter. CONCLUSIONS: The
      high incidence of TDIs reported in toddlers in this study indicates that there is
      an under-reporting of TDIs in previously reported studies. The research design
      used in the present study has an advantage and should be tested in further
      studies.

PMID- 29600501
TI  - Antibiotic distribution, risk assessment, and microbial diversity in river water
      and sediment in Hong Kong.
AB  - For the past fewer years, environment antibiotic residues have got more and more
      attention. The occurrence and distribution of eight common antibiotics, belonging
      to five classes, were determined in both water and sediment of eleven rivers of
      Hong Kong. The target antibiotics were found to be widely distributed.
      Sulfamethoxazole (n.d.-79.9 ng/L), sulfadimidine (n.d.-29.9 ng/L), and ofloxacin
      (n.d.-75.5 ng/L) were the dominant antibiotics in river water, with detection
      rates of 84.6, 76.9, and 69.2%, respectively. Tetracycline (n.d.-9.8 ng/g) was
      the dominant antibiotic in sediment, with a detection rate of 60%. The
      concentrations of all antibiotics in river water of Hong Kong were lower than
      which in various rivers of Europe, North America and Australia, as well as the
      Pearl River Basin of China. All sediment sites exhibited significant bacterial
      diversity. Gammaproteobacteria (0.08-12.7%) and Flavobacteria (0.14-14.1%) were
      the dominant bacterial classes in all sediments. The bacterial compositions
      varied between sites; areas polluted with high levels of antibiotics had rich and
      highly diverse bacterial communities. The environmental risk assessment
      determined that the antibiotics in 73.1% of the samples posed ecological risks to
      algae, and two samples posed low risks to invertebrates. Ofloxacin was the main
      contributor of risk to aquatic organisms, while the antibiotics in 11.5% of the
      samples posed resistance selection risks. The occurrence and distribution of
      eight common antibiotics, belonging to five classes, were widely distributed in
      Hong Kong. Sulfamethoxazole, sulfadimidine, and ofloxacin were the dominant
      antibiotics in river waters, Tetracycline was the dominant antibiotic in
      sediment. Areas polluted with high levels of antibiotics had rich and highly
      diverse bacterial communities. Antibiotics in 73.1% of the samples posed
      ecological risks, while the antibiotics in 11.5% of the samples posed resistance
      selection risks.

PMID- 29600502
TI  - Tracking the elusive 5' exonuclease activity of Chlamydomonas reinhardtii RNase
      J.
AB  - KEY MESSAGE: Chlamydomonas RNase J is the first member of this enzyme family that
      has endo- but no intrinsic 5' exoribonucleolytic activity. This questions its
      proposed role in chloroplast mRNA maturation. RNA maturation and stability in the
      chloroplast are controlled by nuclear-encoded ribonucleases and RNA binding
      proteins. Notably, mRNA 5' end maturation is thought to be achieved by the
      combined action of a 5' exoribonuclease and specific pentatricopeptide repeat
      proteins (PPR) that block the progression of the nuclease. In Arabidopsis the 5'
      exo- and endoribonuclease RNase J has been implicated in this process. Here, we
      verified the chloroplast localization of the orthologous Chlamydomonas (Cr) RNase
      J and studied its activity, both in vitro and in vivo in a heterologous B.
      subtilis system. Our data show that Cr RNase J has endo- but no significant
      intrinsic 5' exonuclease activity that would be compatible with its proposed role
      in mRNA maturation. This is the first example of an RNase J ortholog that does
      not possess a 5' exonuclease activity. A yeast two-hybrid screen revealed a
      number of potential interaction partners but three of the most promising
      candidates tested, failed to induce the latent exonuclease activity of Cr RNase
      J. We still favor the hypothesis that Cr RNase J plays an important role in RNA
      metabolism, but our findings suggest that it rather acts as an endoribonuclease
      in the chloroplast.

PMID- 29600503
TI  - Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on
      Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ).
AB  - INTRODUCTION: To measure the burden of pharmacotherapy on patients with type 2
      diabetes mellitus (T2DM), we developed the Diabetes Treatment Burden
      Questionnaire (DTBQ), a patient-administered questionnaire composed of 18
      questions, and evaluated its reproducibility and validity. METHODS: We enrolled
      240 patients with T2DM under pharmacotherapy over 20 years of age at seven
      institutes in Japan. Their physicians filled out report forms on patient
      backgrounds, and the patients answered both the DTBQ and the Diabetes Treatment
      Satisfaction Questionnaire (DTSQ). For evaluation of reproducibility, 48 of the
      enrolled subjects completed a 2nd DTBQ at home after leaving the medical
      institutes. RESULTS: Statistical analyses were performed for two sets of
      subjects, the validity analysis set (N = 236) and the reproducibility analysis
      set (N = 47). Factor analysis found a simple structure in the DTBQ item scores
      using a three-factor model with varimax rotation; the three subscales were
      designated as "implementation burden", "flexibility burden", and "blood glucose
      control burden". All intraclass correlation coefficients for the subscale scores
      were 0.8 or higher, indicating high reproducibility. Negative correlations were
      observed between the DTSQ satisfaction score and the DTBQ subscale scores.
      Moreover, as the dosing frequency of diabetic medicines increased, the DTBQ total
      score (total burden score) also became higher. Likewise, expected associations
      were observed between patient backgrounds and DTSQ scores. CONCLUSION: The DTBQ
      has adequate reproducibility and validity as a measurement scale for treatment
      burden on T2DM patients. TRIAL REGISTRATION: University Hospital Medical
      Information Network (UMIN) 000026382. FUNDING: Eli Lilly Japan.

PMID- 29600505
TI  - The Economic Burden of Insulin-Related Hypoglycemia in Adults with Diabetes: An
      Analysis from the Perspective of the Italian Healthcare System.
AB  - INTRODUCTION: The aim of this analysis was to estimate the cost of insulin
      related hypoglycemia in adult patients with diabetes in Italy using the Local
      Impact of Hypoglycemia Tool (LIHT), and to explore the effect of different
      hypoglycemia rates on budget impact. METHODS: Direct costs and healthcare
      resource utilization were estimated for severe and non-severe hypoglycemic
      episodes in Italy and applied to the population of adults with type 1 diabetes
      (T1DM) and type 2 diabetes (T2DM) and their corresponding hypoglycemia episode
      rates (0.49 severe and 53.3 non-severe episodes per year for T1DM, and 0.09
      severe and 9.3 non-severe episodes per year for T2DM). Uncertainty around model
      inputs was explored through sensitivity and scenario analyses. RESULTS: The
      direct cost of insulin-related hypoglycemia in Italy is estimated at ?144.7
      million per year, with ?65 million attributable to severe episodes and ?79.6
      million due to non-severe episodes. The total cost of hypoglycemia is
      approximately 1.7-fold higher for T2DM (?91.7 million) than for T1DM (?53
      million). The cost of a hypoglycemic episode ranges from ?4.59 for a non-severe
      event where additional self-monitoring of blood glucose (SMBG) testing is the
      only cost incurred, to ?5790.59 for a severe event that also requires an
      ambulance, A&E, hospitalization, and a visit to a diabetes specialist. A
      reduction in hypoglycemia event rates could result in substantial cost savings;
      for example, a 20% reduction in severe and non-severe hypoglycemia rates could
      result in a saving of ?47,769 per general population of 100,000 people.
      CONCLUSIONS: The LIHT highlights the substantial economic burden of insulin
      related hypoglycemia in Italy, particularly with regards to non-severe
      hypoglycemia, an aspect of hypoglycemia that is often overlooked. This analysis
      may aid healthcare decision-making by allowing the costs of insulin therapies or
      diabetes self-management programs to be balanced with the savings provided by
      reductions in hypoglycemia. FUNDING: Novo Nordisk, UK.

PMID- 29600504
TI  - Clinical Trajectories, Healthcare Resource Use, and Costs of Diabetic Nephropathy
      Among Patients with Type 2 Diabetes: A Latent Class Analysis.
AB  - INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are clinically
      heterogeneous in terms of disease severity, treatment, and comorbidities,
      potentially resulting in differential diabetic nephropathy (DN) progression
      courses. In this exploratory study we used latent class analysis (LCA) to
      identify patient groups with distinct clinical profiles of T2DM severity and
      explored the association between disease severity, DN progression or reversal,
      and healthcare resource use (HRU) and costs. METHODS: Latent class analysis was
      used to group adults with >=  2 medical claims with a diagnosis of T2DM and >= 2
      urine albumin tests within the Truven MarketScan database (2004-2014), based on
      T2DM-related complications, comorbidities, and therapies. DN severity categories
      (normoalbuminuria, moderately increased albuminuria, and severely increased
      albuminuria) were determined based on urine albumin measure. The risks of DN
      progression and reversal (change to a more/less severe DN category) were compared
      among all identified latent classes using Kaplan-Meier analyses and log-rank
      tests. All-cause and DN-related costs and HRU were assessed and compared during
      the study period among the identified latent classes. RESULTS: Four clinically
      distinct profiles were identified among the 23,235 eligible patients: low
      comorbidity/low treatment (46.5%), low comorbidity/high treatment (29.0%),
      moderate comorbidity/high insulin use (9.7%), and high comorbidity/moderate
      treatment (14.8%). The 5-year DN progression rates for these clinically distinct
      profiles were 11.8, 18, 16.5, and 27.7%, respectively. Compared with the low
      comorbidity/low treatment group, all other groups were associated with an
      increased risk of DN progression (all p < 0.001). Increasing comorbidity was
      significantly associated with higher all-cause and DN-related HRU and costs,
      primarily driven by higher pharmacy and inpatient costs. CONCLUSION: Patients
      with T2DM who have more comorbidities experienced higher rates of DN progression
      and HRU and incurred higher healthcare costs compared with patients with low
      comorbidity profiles. Future prospective studies are needed to confirm the
      significance of these groups on DN progression, HRU, and costs. FUNDING: Takeda
      Development Center Americas, Inc.

PMID- 29600506
TI  - Prediabetes Directly Deteriorates into Diabetic Ketoacidosis and Hyperosmolar
      Hyperglycemic Syndrome Triggered by Acute Pancreatitis: A Case Report
      Illustrating a "Chicken and Egg" Paradigm in Ketosis-Prone Diabetes.
AB  - INTRODUCTION: Diabetic crises occur most often in patients with type 1 diabetes
      and occasionally in type 2 diabetes, especially under stressful conditions.
      However, a diabetic crisis occurring directly from prediabetes is an unusual
      phenomenon. CASE REPORT: A 45-year-old woman presented with postprandial left
      upper quadrant abdominal pain, nausea, and vomiting. She had a past medical
      history of prediabetes with impaired fasting glucose and HbA1c 6.4%. On
      admission, routine laboratory tests showed high anion gap metabolic acidosis (pH
      6.92), anion gap 41 mmol/L, blood glucose 931 mg/dL, beta-hydroxybutyrate 28
      mmol/L, and calculated effective osmolarity 322 mOsm/kg; she was diagnosed with
      diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS), and
      DKA-related abdominal pain. Later, the patient was found to have elevated lipase
      and amylase, and diagnosed with acute pancreatitis. Since DKA can induce
      abdominal pain and nonspecific lipase elevation, both of which are
      characteristics of acute pancreatitis, while acute pancreatitis can conversely
      trigger DKA, there exists a "chicken and egg" paradigm. Therefore, the
      differential diagnosis is discussed. CONCLUSION: It is important to differentiate
      DKA from concomitant causes of abdominal pain to avoid missing the underlying
      etiology, which can be the trigger for DKA. During diabetic crises, treating the
      underlying trigger is just as important as managing metabolic derangements in
      order to achieve favorable outcomes; meanwhile, managing acute pancreatitis
      associated hyperglycemia can promote recovery. Additionally, diabetic crisis that
      directly evolves from prediabetes illustrates an atypical form of diabetes called
      ketosis-prone diabetes; we briefly discuss its clinical characteristics,
      classification, and follow-up.

PMID- 29600507
TI  - Probability of Achieving Glycemic Control with Basal Insulin in Patients with
      Type 2 Diabetes in Real-World Practice in the USA.
AB  - INTRODUCTION: Basal insulin (BI) plays an important role in treating type 2
      diabetes (T2D), especially when oral antidiabetic (OAD) medications are
      insufficient for glycemic control. We conducted a retrospective, observational
      study using electronic medical records (EMR) data from the IBM(r) Explorys
      database to evaluate the probability of achieving glycemic control over 24 months
      after BI initiation in patients with T2D in the USA. METHODS: A cohort of 6597
      patients with T2D who started BI following OAD(s) and had at least one valid
      glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720
      days after BI initiation were selected. We estimated the changes from baseline in
      HbA1c every 6 months, the quarterly conditional probabilities of reaching HbA1c <
      7% if a patient had not achieved glycemic control prior to each quarter (Q), and
      the cumulative probability of reaching glycemic control over 24 months. RESULTS:
      Our cohort was representative of patients with T2D who initiated BI from OADs in
      the USA. The average HbA1c was 9.1% at BI initiation, and decreased robustly
      (1.5%) in the first 6 months after initiation with no further reductions
      thereafter. The conditional probability of reaching glycemic control decreased
      rapidly in the first year (26.6% in Q2; 17.6% in Q3; 8.6% in Q4), and then
      remained low (<= 6.1%) for each quarter in the second year. Cumulatively, about
      38% of patients reached HbA1c < 7% in the first year; only approximately 8% more
      did so in the second year. CONCLUSION: Our study of real-world data from a large
      US EMR database suggested that among patients with T2D who initiated BI after
      OADs, the likelihood of reaching glycemic control diminished over time, and
      remained low from 12 months onwards. Additional treatment options should be
      considered if patients do not reach glycemic control within 12 months of BI
      initiation. FUNDING: Sanofi Corporation.

PMID- 29600508
TI  - Correction to: Molecular Characterization of Pneumococcal Surface Protein A
      (PspA), Serotype Distribution and Antibiotic Susceptibility of Streptococcus
      pneumoniae Strains Isolated from Pakistan.
AB  - In the original publication, one of the author names was missed in the author
      group.

PMID- 29600509
TI  - Integrated, Family-based, Partial Hospital Treatment for Complex Pediatric
      Illness.
AB  - This paper describes a unique treatment program for complex pediatric illness.
      The Hasbro Children's Partial Hospital Program uses a family systems orientation,
      integrated care, and a partial hospital setting to treat children with a wide
      range of pediatric illnesses that have failed outpatient and inpatient
      treatments. We have treated more than 2000 children with at least 80 different
      ICD-9 diagnoses. The multidisciplinary treatment team functions as a meta-family
      for children and their families who present with illness and family beliefs that
      impede successful outcomes with standard care. The three features: family systems
      orientation, integrated care, and partial hospital setting, hopefully interact to
      create an environment that helps families expand and modify their explanatory
      models regarding participating in effective medical care. The goal of treatment
      is for both children and their parents to feel empowered to take control of the
      illness. Parents completing standardized measures at intake describe their
      children and families as experiencing significant emotional distress, low levels
      of general family functioning, and poor quality of life. Although the children
      are described as having distinct behavioral differences, the families are
      described as responding to the experience of a seriously ill child in similar
      ways. A treatment program that addresses the noncategorical aspects of how
      families respond to illness while addressing the specific diseases of the
      children can allow children and their families to respond favorably to treatment.

PMID- 29600510
TI  - Gait research in cerebral palsy: should we zoom in or zoom out?

PMID- 29600511
TI  - Increased cerebral blood flow on arterial spin labeling magnetic resonance
      imaging can localize to seizure focus in newborns: A report of 3 cases.
AB  - Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can assess cerebral
      blood flow (CBF) without using radiolabeled tracers. It is unknown whether
      regional increases in CBF on ASL MRI correlate with seizure location in newborns.
      We report 3 newborns with focal seizures localized on continuous video
      electroencephalogram (cEEG), anatomical brain MRI, and ASL MRI. Each patient
      underwent pseudocontinuous ASL with segmented 3-dimensional fast spin echo
      readout as part of standard care. Case 1 is a term male infant presenting with
      left temporal status epilepticus and recurrent cEEG seizures from an idiopathic
      large left intraventricular hemorrhage. ASL images demonstrated left mesial
      temporal lobe increased CBF. Case 2 is a late preterm male infant presenting with
      recurrent cEEG seizures due to focal right megalencephaly. Ictal EEG and ASL
      images coincided with the focal dysplasia. Case 3 is a dysmorphic term female
      infant with nonconvulsive partial status epilepticus identified by focal
      increased CBF of the left temporal lobe on ASL images. The area of increased CBF
      was within an area of extensive left hemisphere dysplasia. To our knowledge, this
      is the first report of regional increases in CBF on ASL MRI correlating with
      ictal cEEG in newborns.

PMID- 29600512
TI  - Prevalence of spinal abnormalities in Chinook salmon smolt and influence of early
      rearing temperature and growth rates.
AB  - Spinal abnormalities can be detected at harvest in around 40% of farmed Chinook
      salmon in New Zealand. However, whether these abnormalities are present in smolt
      is unknown. Radiographs of 3,736 smolt were taken immediately prior to transfer
      to sea water and evaluated for fusions, compressions, vertical shifts, and
      lordosis, kyphosis and/or scoliosis (LKS). The survey included smolt from two
      different chilling strategies that had been graded into slow- or fast-growing
      fish. Overall, 4.34% of Chinook salmon smolt had at least one spinal abnormality,
      similar to the rates of reported in Atlantic salmon smolt. The rate of
      abnormality was significantly higher in faster-growing fish. Fusions were most
      common with 2.68% of smolt affected. Smolt subjected to longer chilling times had
      lower rates of fusions. Compressions and vertical shifts were both observed in
      1.31% of smolt. Although LKS is the most common abnormality of harvested fish,
      LKS was detected in just five smolt. The results suggest that some fusions in
      harvest fish have developed at the time of seawater transfer while LKS develops
      late in the production cycle. Overall, spinal abnormalities are uncommon in
      Chinook salmon smolt and may be influenced by chilling times and growth rates.

PMID- 29600513
TI  - Alcohol hangover impacts learning and reward processing within the medial-frontal
      cortex.
AB  - It is common knowledge that alcohol intoxication impairs motor coordination,
      judgment, and decision making. Indeed, an abundance of literature links
      intoxication to impaired cognitive control that leads to accidents and injury. A
      broadening body of research, however, suggests that the impact of alcohol may
      continue beyond the point of intoxication and into the period of alcohol
      hangover. Here, we examined differences in the amplitude of reward positivity-a
      component of the human ERP associated with learning-between control and hangover
      participants. During performance of a learnable gambling task, we found a
      reduction in the reward positivity during alcohol hangover. Additionally,
      participants experiencing alcohol hangover demonstrated reduced performance in
      the experimental task in comparison to their nonhangover counterparts. Our
      results suggest that the neural systems that underlie performance monitoring and
      reward-based learning are impaired during alcohol hangover.

PMID- 29600514
TI  - Ambient aerosol increases minimum leaf conductance and alters the aperture-flux
      relationship as stomata respond to vapor pressure deficit (VPD).
AB  - Aerosols are important components of the global plant environment, with
      beneficial and deleterious impacts. The direct effects of aerosol deposition on
      plant-water relationships remain poorly characterized but potentially important.
      Vicia faba was grown in ambient urban air and in the same air with aerosol
      excluded, in a moderately polluted environment using two exposure protocols.
      Simultaneous measurement of gas exchange and stomatal pore aperture was combined
      with leaf dehydration kinetics and microscopic evaluation of leaf wetness
      formation and aerosol deposition patterns. The ambient aerosol was shown to be
      hygroscopic. Aerosol exposure increased minimum leaf conductance, shown by
      dehydration kinetics, and nocturnal water vapor flux, shown by dark-adapted gas
      exchange. Aerosol exposure decreased stomatal apertures at each level of vapor
      pressure deficit (VPD) and increased stomatal conductance at comparable levels of
      aperture. Overall, these effects were modest, and largest when stomata were wide
      open. The uncoupling of conductance (flux-based) from aperture (directly measured
      microscopically) implies that aerosol-induced water loss is not fully under
      stomatal control. This reduces drought tolerance and may provide a mechanism by
      which deposited aerosol plays a direct role in stomatal response to VPD.

PMID- 29600516
TI  - Obliquely-arranged double skin paddles: A novel design to reconstruct extensive
      head and neck defects with a single fibula or peroneal flap.
AB  - OBJECTIVE: To reconstruct extensive head and neck defects usually necessitates
      double free flaps, which require a time-and-manpower-consuming surgical
      procedure. We present using a single fibula or peroneal flap with the novel
      design of obliquely-arranged double skin paddles to reconstruct an extensive head
      and neck defect. METHODS: From 1998 to 2016, eight patients with the age of 52.25
      (35-71) years old had extensive head and neck defects after oral cancer ablation.
      All of the defects were through and through with the size of 16.25 (12-24) cm *
      8.8 (4.5-11) cm. Six of the defects were due to buccal cancer. One was due to
      tongue cancer, and another one was due to gingiva cancer. All the defects were
      reconstructed with obliquely-arranged double-paddle free fibula or peroneal
      flaps. The long axis of the skin paddles was arranged at certain angle (30-45
      degrees) to the long axis of lower leg, and the two separate skin paddles were
      used as the form of island flaps by isolating the cutaneous perforators to create
      a true chimeric flap. RESULTS: The skin paddle sizes were 14 cm * 3 cm-24 cm * 11
      cm and 9.5 cm * 4.5 cm-13 cm * 8 cm. The average length of harvested fibula was
      19 (10-30) cm. All of the eight flaps survived without obvious donor site
      morbidity. One patient had partial skin necrosis over recipient site, requiring
      surgical debridements and closure. One patient had superficial necrosis over the
      edge of outer skin paddle, which healed spontaneously. After the follow-up
      periods of 1 month to 3 year and 8 months, two patients died of sepsis. Six of
      them could resume soft diet and had no saliva drooling. The remaining two
      remained nasogastric diet and had saliva drooling. CONCLUSION: With the design of
      obliquely-arranged double paddles, we may maximize the harvested skin area of
      lateral lower leg to reconstruct an extensive head and neck defect with a single
      free flap.

PMID- 29600515
TI  - Developing drugs for treatment of atopic dermatitis in children (>=3 months to
      <18 years of age): Draft guidance for industry.
AB  - Atopic dermatitis is the most common chronic skin disease, and it primarily
      affects children. Although atopic dermatitis (AD) has the highest effect on
      burden of skin disease, no high-level studies have defined optimal therapy for
      severe disease. Corticosteroids have been used to treat AD since the 1950s and
      remain the only systemic medication with Food and Drug Administration approval
      for this indication in children, despite published guidelines of care that
      recommend against this option. Several clinical trials with level 1 evidence have
      supported the use of topical treatments for mild to moderate atopic dermatitis in
      adults and children, but these trials have had little consistency in protocol
      design. Consensus recommendations will help standardize clinical development and
      trial design for children. The Food and Drug Administration issues guidance
      documents for industry as a source for "the Agency's current thinking on a
      particular subject." Although they are nonbinding, industry considers these
      documents to be the standard for clinical development and trial design. Our
      consensus group is the first to specifically address clinical trial design in
      this population. We developed a draft guidance document for industry, Developing
      Drugs for Treatment of Atopic Dermatitis in Children (>=3 months to <18 years of
      age). This draft guidance has been submitted to the Food and Drug Administration
      based on a provision in the Federal Register (Good Guidance Practices).

PMID- 29600517
TI  - The impact of length of stay on recovery measures in faith-based addiction
      treatment.
AB  - OBJECTIVE: To determine the impact of length of stay among homeless men in faith
      based residential addictions recovery on physical activity, depression, self
      esteem, and nicotine dependence. DESIGN AND SAMPLE: A time series design was
      utilized to measure changes in the four quality measures at program entry and at
      3, 6, and 9 months following admission. The sample consisted of 175 homeless
      residents enrolled in a faith-based residential recovery program. MEASURES:
      Paired t tests were used to determine the change in average instrument response
      from admission to each follow-up period. Analysis of variance (ANOVA) and Tukey
      posthoc tests were used to assess for differences in length of stay between
      demographic variables. RESULTS: Statistically significant improvements were noted
      in self-esteem and depressive symptomatology at 3 and 6 months following
      admission and in physical activity levels at 3 months following admission.
      Nicotine dependence scores declined at 3 and 6 months but were not statistically
      significant. CONCLUSION: Time spent in this faith-based spiritual recovery
      program had a significant impact on depression, self-esteem, and physical
      activity. Recommendations for future study include conducting research to analyze
      the relationship between distinct program elements and quality indicators and
      comparing faith-based programs to other similar programs and to publicly funded
      secular recovery programs.

PMID- 29600518
TI  - Dynamics of arbuscular mycorrhizal fungal community structure and functioning
      along a nitrogen enrichment gradient in an alpine meadow ecosystem.
AB  - Nitrogen (N) availability is increasing dramatically in many ecosystems, but the
      influence of elevated N on the functioning of arbuscular mycorrhizal (AM) fungi
      in natural ecosystems is not well understood. We measured AM fungal community
      structure and mycorrhizal function simultaneously across an experimental N
      addition gradient in an alpine meadow that is limited by N but not by phosphorus
      (P). AM fungal communities at both whole-plant-community (mixed roots) and single
      plant-species (Elymus nutans roots) scales were described using pyro-sequencing,
      and the mycorrhizal functioning was quantified using a mycorrhizal-suppression
      treatment in the field (whole-plant-community scale) and a glasshouse inoculation
      experiment (single-plant-species scale). Nitrogen enrichment progressively
      reduced AM fungal abundance, changed AM fungal community composition, and shifted
      mycorrhizal functioning towards parasitism at both whole-plant-community and E.
      nutans scales. N-induced shifts in AM fungal community composition were tightly
      linked to soil N availability and/or plant species richness, whereas the shifts
      in mycorrhizal function were associated with the communities of specific AM
      fungal lineages. The observed changes in both AM fungal community structure and
      functioning across an N enrichment gradient highlight that N enrichment of
      ecosystems that are not P-limited can induce parasitic mycorrhizal functioning
      and influence plant community structure and ecosystem sustainability.

PMID- 29600519
TI  - Transgenic soybean plants expressing Spb18S dsRNA exhibit enhanced resistance to
      the soybean pod borer Leguminivora glycinivorella (Lepidoptera: Olethreutidae).
AB  - The soybean pod borer [SPB; Leguminivora glycinivorella (Mats.) Obraztsov] is a
      major soybean pest in northeastern Asia. A useful method for addressing this
      problem is the generation of transgenic plants producing double-stranded RNA
      (dsRNA) that target essential insect genes. In this study, we confirmed that 18S
      ribosomal RNA is critical for SPB development. Downregulated Spb18S expression
      induced by dsRNA injection increased larval mortality rates and resulted in early
      pupation. We also assessed whether Spb18S is silenced in SPB larvae fed on
      transgenic soybean expressing Spb18S dsRNA. Transgenic plants downregulated
      Spb18S expression levels and second-instar larval survival rates. Moreover, such
      plants were less damaged by SPB larvae than control plants under field
      conditions.

PMID- 29600520
TI  - Identification of differentially regulated deceitful proteins in SH-SY5Y cells
      engineered with Tet-regulated protein expression system.
AB  - Tetracycline regulated protein expression in mammalian cells is a powerful tool
      to predict the physiological function, cellular localization, and stability of a
      protein. In addition, to predict metabolic networks affected by the expression of
      wild-type or mutant forms of proteins, researchers generally produce a single
      mammalian cell clone that can express the protein of interest under tetracycline
      control and study the changes occurring in overall proteome before and after
      expression of a protein of interest. One limitation of tetracycline regulated
      clonal cell creation, however, is that it sometimes creates clones with changed
      protein levels even without the expression of the protein of interest due to the
      nonspecific insertion of the gene encoding the protein of interest into the
      genome or disruption of a metabolic pathway due to insertional silencing or
      activation. The aim of this study was to demonstrate the limitation of
      tetracycline regulated gene expression by creating clonal cell lines expressing
      the wild-type or the mutant forms of Fat mass and obesity-associated protein.
      Comparative proteome analysis of the protein extracts by two-dimensional gel
      electrophoresis coupled to MALDI-TOF/TOF revealed the presence of eight proteins
      subjected to differential regulation even in the absence of induction. The
      identified proteins were 14-3-3 protein Epsilon, Vimentin, Heterogeneous nuclear
      ribonucleoprotein K, Tubulin beta-2C chain, Heat shock protein HSP 90-alpha, Heat
      shock protein HSP 90-beta, Alpha-enolase, TATA-binding protein-associated factor
      2N. An ultimate care should be taken to prevent reporting of deceitful proteins
      generated from studies utilizing tetracycline regulated gene expression systems.

PMID- 29600521
TI  - Phytosomal-curcumin antagonizes cell growth and migration, induced by thrombin
      through AMP-Kinase in breast cancer.
AB  - Here we explored the antitumor-activity of novel-formulated-form of curcumin
      (phytosomal-encapsulated-curcumin) or in combination with 5-FU in breast cancer.
      The antiproliferative activity was assessed in 2D and 3-dimensional cell-culture
      model. The migratory-behaviors of the cells were determined by migration assay.
      The expression levels of CyclinD1,GSK3a/b, P-AMPK, MMP9, and E-cadherin were
      studied by qRT-PCR and/or Western blotting. The anti-inflammatory of nano
      curcumin was assessed, while antioxidant activity was evaluated by
      malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total
      thiols (T-SH). To understand dynamic behavior of genes, we reconstructed a
      Boolean network, while the robustness of this model was evaluated by Hamming
      distance. phytosomal-curcumin suppressed cell-growth followed by tumor-shrinkage
      in 3D model through perturbation of AMP-activated protein kinase. Curcumin
      reduced the invasiveness of MCF-7 through perturbation of E-cadherin. Moreover,
      phytosomal-curcumin inhibited the tumor growth in xerograph model. Histological
      staining of tumor tissues revealed vascular disruption and RBC extravasation,
      necrosis, tumor stroma, and inflammation. Co-treatment of curcumin and 5-FU
      reduced the lipid-peroxidation and increased MDA/SOD level. Of note, curcumin
      reduced cyclinD-expression in breast cancer cell treated with thrombin, and
      activates AMPK in a time-dependent manner. Also suppression of AMPK abrogated
      inhibitory effect of phytosomal-curcumin on thrombin-induced cyclin D1 over
      expression, suggesting that AMPK is essential for anti-proliferative effect of
      this agent in breast cancer. Our finding demonstrated that phytosomal-curcumin
      antagonizes cell growth and migration, induced by thrombin through AMP-Kinase in
      breast cancer, supporting further-investigations on the therapeutic potential of
      this novel anticancer agent in treatment of breast cancer.

PMID- 29600522
TI  - Studies on the effects of LPS, beta-glucan and metabolic inhibitors on the
      respiratory burst and gene expression in Atlantic salmon macrophages.
AB  - Reactive oxygen species (ROS) production in macrophage-like cells is induced as
      an antimicrobial defence against invading pathogens. In this study, we have
      explored how different stimuli and metabolic inhibitors affect the level of
      respiratory burst in Atlantic salmon (Salmo salar L.) head kidney macrophage-like
      cells. Cells stimulated in vitro by bacterial lipopolysaccharide (LPS) and beta
      glucan showed increased production of ROS compared to unstimulated cells. Both
      stimulation and costimulation by curdlan (beta-glucan) induced a higher
      production of ROS compared to stimulation and costimulation by LPS. Metabolic
      inhibitors co-incubated with the stimulants did not, in most cases, perturb the
      level of ROS generation in the salmon macrophage-like cells. The NAD+ content as
      well as the NAD+ /NADH ratio increased in curdlan and LPS + curdlan-stimulated
      cells compared to control cells, which indicated increased metabolic activity in
      the stimulated cells. Supporting these findings, gene analysis using real-time
      quantitative PCR showed that arginase-1 and IL-1beta genes were highly expressed
      in the stimulated cells.

PMID- 29600523
TI  - Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the
      prognostic value of the Marseille Grading System in a cohort of 132 patients.
AB  - The finding that meningeal solitary fibrous tumors (SFTs) and meningeal
      hemangiopericytomas (HPCs) are both characterized by NAB2-STAT6 gene fusion has
      pushed their inclusion in the WHO 2016 Classification of tumors of the central
      nervous system (CNS) as different manifestations of the same entity. Given that
      the clinical behavior of the CNS SFT/HPC spectrum ranges from benign to
      malignant, it is presently unclear whether the grading criteria are still
      adequate. Here, we present the results of a study that analyzed the prognostic
      value of an updated version of the Marseille Grading System (MGS) in a
      retrospectively assembled cohort of 132 primary meningeal SFTs/HPCs with nuclear
      overexpression of STAT6. The median patient follow-up was 64 months (range 4-274
      months); 73 cases (55%) were MGS I, 50 cases (38%) MGS II and 9 cases (7%) were
      MGS III. Progression-free survival (PFS) and disease-specific survival (DSS) were
      investigated using univariate analysis: the prognostic factors for PFS included
      MGS, extent of surgery, radiotherapy, chemotherapy and mitotic activity >=5/10
      high-power field (HPF). Moreover, MGS, radiotherapy, mitotic activity >=5/10 HPF,
      and necrosis were the prognostic factors measured for DSS. In multivariate
      analysis, extent of surgery, mitotic activity >=5/10 HPF, MGS I and MGS III were
      the independent prognostic factors measured for PFS while necrosis, MGS III and
      radiotherapy were the independent prognostic factors for DSS. In conclusion, our
      results show that assessing the malignancy risk of SFT/HPC should not rely on one
      single criterion like mitotic activity. Therefore, MGS is useful as it combines
      the value of different criteria. In particular, the combination of a high mitotic
      activity and necrosis (MGS III) indicates a particularly poor prognosis.

PMID- 29600524
TI  - Symptom experiences in patients with advanced pancreatic cancer as reported
      during healthcare encounters.
AB  - Symptom management is one of the primary goals of care for advanced pancreatic
      cancer (APC) patients. The purpose of this study was to examine recorded
      healthcare encounters to better understand the symptom experiences of APC
      patients as told to healthcare providers (HCP). In this qualitative descriptive
      study, content analysis was used to analyze 37 transcripts of audio-recorded,
      naturally occurring encounters among APC patients, caregivers, and HCP.
      Transcripts were drawn from a larger randomized controlled study, which recruited
      advanced cancer patients and caregivers across the United States. Findings
      revealed that APC patients and caregivers experienced multiple troubling
      symptoms. Thirty-seven APC patients and 34 caregivers discussed 10 types of
      symptoms: pain, fatigue, abnormal bowel movements, decreased appetite, nausea and
      vomiting, sleeping problems, neurological problems, skin problems, psychological
      distress, and taste changes. The patients and caregivers discussed various
      aspects of the symptoms, including the nature of the symptoms, how the symptoms
      affected their lives, and the way they managed symptoms. Some symptoms were
      described as severe, life-changing, and highly distressing. HCP should be attuned
      to the wide variety of ways in which APC patients experience, manage, and live
      with symptoms. A systematic approach to address symptoms during encounters may
      improve care and efficiency.

PMID- 29600525
TI  - Thiacloprid-induced toxicity influenced by nutrients: Evidence from in situ
      bioassays in experimental ditches.
AB  - Many studies show that neonicotinoid insecticides cause toxicity to aquatic
      invertebrates. Some studies report that insecticide toxicity may differ in
      combination with other agrochemicals under realistic field conditions. To explore
      such altered toxicity further, we aimed to determine the single and combined
      effects of environmentally relevant levels of the neonicotinoid thiacloprid and
      nutrients on different endpoints of 4 aquatic invertebrate species. Animals were
      exposed to these agrochemicals using a caged experiment within experimental
      ditches. We observed thiacloprid-induced toxicity for 2 crustaceans, Daphnia
      magna and Asellus aquaticus, and for 1 out of 2 tested insect species, Cloeon
      dipterum. We observed no toxic effects for Chironomus riparius at the time
      weighted average test concentration of 0.51 MUg thiacloprid/L. For D. magna, the
      observed toxicity, expressed as the lowest-observed-effect concentration (LOEC),
      on growth and reproduction was present at thiacloprid concentrations that were
      2456-fold lower than laboratory-derived LOEC values. This shows that these
      species, when exposed under natural conditions, may exhibit neonicotinoid-induced
      toxic stress. Contrary to the low nutrient treatment, such toxicity was often not
      observed under nutrient-enriched conditions. This was likely attributable to the
      increased primary production that allowed for compensatory feeding. These
      findings warrant the inclusion of different feeding regimes in laboratory
      experiments to retrieve the best estimates of neonicotinoid-induced toxicity in
      the natural environment. Environ Toxicol Chem 2018;37:1907-1915. (c) 2018 SETAC.

PMID- 29600526
TI  - First characterization of fucosidases in spiders.
AB  - l-fucose is a constituent of glycoconjugates in different organisms. Fucosidases
      catalyze the removal of fucose residues, and have been correlated to different
      physiological and pathological processes, such as fertilization, cancer,
      fucosidosis, and digestion in molluscs and ticks. An alpha-l-fucosidase sequence
      was identified from the transcriptome and proteome from the midgut diverticula of
      the synanthropic spider Nephilingis cruentata. In this article, we describe the
      isolation of this alpha-l-fucosidase and the characterization of its activity
      using substrates and inhibitors demonstrating different specificities among
      fucosidases. The enzyme had a Km of 32 and 400 MUM for 4-methylumbelliferyl alpha
      l-fucopyranoside and 4-nitrophenyl alpha-l-fucopyranoside, respectively; and was
      unable to hydrolyze fucoidan. Nephilingis cruentata alpha-l-fucosidase was
      inhibited competitively by fucose and fuconojyrimycin. The fucosidase had two
      distinct pH optima even in the isolated form, due to oligomerization dependent on
      pH, as previously described to other fucosidases. Alignment and molecular
      homology modeling of the protein sequence with other fucosidases indicated that
      the active sites and catalytic residues were different, including residues
      involved in acid/base catalysis. Phylogenetic analysis showed, for the first
      time, gene-duplication events for fucosidases in Arachnida species. All these
      data reveal that studies on fucosidases in organisms distinct from bacteria,
      fungi, and humans are important.

PMID- 29600527
TI  - In response to: Heise T, Norskov M, Nosek L, Kaplan K, Famulla S and Haahr H. L.
      (2017) Insulin degludec: Lower day-to-day and within-day variability in
      pharmacodynamic response compared to insulin glargine U300 in type 1 diabetes.
      Diabetes Obes Metab. 2017;19:1032-1039.

PMID- 29600528
TI  - "Bottom-Up" Fabrication of BODIPY-Functionalized Fluorescent Hyperbranched
      Glycopolymers for Hepatoma-Targeted Imaging.
AB  - A novel type of multivalent and highly specific fluorescent hyperbranched
      glycopolymers h-P(GalEA-co-VBPT-co-BYMA) (hPGVB) is designed and prepared
      successfully via a facile "bottom-up" strategy. The acetylated hPGVB is prepared
      by one-pot reversible addition-fragmentation chain transfer (RAFT)
      copolymerization of acrylate-type galactose monomers AcGalEA and methacrylate
      type fluorescent monomers BYMA in presence of an inimer-type RAFT chain transfer
      agent. After deacetylation, the resulting amphiphilic hPGVB can self-assemble
      into stable nanoparticles in aqueous media, showing strong green fluorescence
      with relative high quantum yields and good photostability. The cell viability
      study indicates the excellent biocompatibility of the hPGVB fluorescent
      nanoparticles (FNPs) against HepG2 and NIH3T3 cells. More importantly, comparing
      with the galactose-free fluorescent hyperbranched polymers h-P(OEGMA-co-VBPT-co
      BYMA), hPEVB FNPs can be selectively internalized by asialoglycoprotein (ASGP)
      receptor-rich HepG2 cells, indicating their potential application in the
      bioimaging fields.

PMID- 29600529
TI  - Catalytic Reduction of Molecular Dinitrogen to Ammonia and Hydrazine Using
      Vanadium Complexes.
AB  - Newly designed and prepared vanadium complexes bearing anionic pyrrole-based PNP
      type pincer and aryloxy ligands were found to work as effective catalysts for the
      direct conversion of molecular dinitrogen into ammonia and hydrazine under mild
      reaction conditions. This is the first successful example of vanadium-catalyzed
      dinitrogen reduction under mild reaction conditions.

PMID- 29600530
TI  - Does a blended learning environment suit advanced practice training for
      pharmacists in a Middle East setting?
AB  - OBJECTIVES: The transfer of pedagogies and instructional techniques outside their
      contexts of origin may not be always be suitable for intended learners. The aim
      of this study was to explore the experiences of Middle East pharmacists enrolled
      in advanced pharmacy practice courses delivered through a blended learning
      environment (BLE). METHODS: Seventeen students and graduates from a BLE in Qatar
      participated in focus group interviews. A topic guide was developed to elicit
      these pharmacists' perspectives on perceived barriers to completing the courses
      and facilitating factors for content engagement and overall satisfaction.
      Discussions were recorded, transcribed verbatim and text analysed using thematic
      content analysis. KEY FINDINGS: We identified three predominant themes in our
      analysis of these discussions: (1) relevance, (2) motivation and (3)
      communication. Participants favourably endorsed any programme aspect that linked
      with their workplace care responsibilities, but found it challenging to adapt to
      high-fidelity testing environments. The on-campus sessions were key for
      sustaining motivation and recommitting to time management and organisation with
      the distance-based content. Although these students expressed difficulty in
      understanding posted assignment instructions and feedback and occasionally faced
      technological issues, they were overwhelmingly satisfied with how the programme
      contributed to advancing their practice capabilities. CONCLUSIONS: Pharmacists
      enrolled in BLE advanced pharmacy practice courses in Qatar identified barriers
      and facilitators like those experienced by professional learners elsewhere.
      However, we found that instructional design and communication approaches merit
      some special consideration for Arab students for optimal engagement in BLE.

PMID- 29600531
TI  - From S,N-Heteroacene to Large Discotic Polycyclic Aromatic Hydrocarbons (PAHs):
      Liquid Crystal versus Plastic Crystalline Materials with Tunable Mechanochromic
      Fluorescence.
AB  - A novel type of discotic polycyclic aromatic hydrocarbon (PAH) based on an
      enlarged dibenzo[a,c]phenazine core has been developed. The large conjugated
      mesogenic core with increased dipole moment derived from S,N heteroatoms
      facilitates the formation of highly ordered columnar superstructures both in
      solution and bulk. Columnar mesophases, including liquid crystal (LC) and plastic
      crystal (PC) assemblies could form unprecedentedly based on the same PAH core.
      The cores are delicately modulated by the peripherical alkoxy chains. Both
      mesogens have mechanochromic fluorescent (MCF) character, which is also structure
      dependent and correlated with the different mesophase formation. For the first
      time, MCF properties can be realized in such a large conjugated mesogenic system.

PMID- 29600532
TI  - Sertoli cells for cell transplantation: pre-clinical studies and future
      perspectives.
AB  - Sertoli cells are located in the testes where they control several key functions
      in spermatogenesis. Over the past 30 years, Sertoli cells have been upgraded from
      a simple scaffold-like structural system to a dynamic functional system of
      intercellular support that delivers potent immunomodulatory and trophic factors.
      Since the discovery of new Sertoli cell secretory products, these cells have been
      utilized in experimental cell transplantation and co-transplantation protocols
      aimed at treating both chronic inflammatory and degenerative disorders. For these
      reasons, this work reviews the application of both naked and microencapsulated
      Sertoli cells used in cell transplantation studies of several chronic or
      autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne
      muscular dystrophy and in studies aimed at the prevention of skin allograft
      rejection.

PMID- 29600533
TI  - Peptide-Based Scaffold for Nitric Oxide Induced Differentiation of Neuroblastoma
      Cells.
AB  - Nitric oxide is a gaseous messenger involved in neuronal differentiation,
      development and synaptogenesis, in addition to many other physiological
      functions. Therefore, it is imperative to maintain an optimal nitric oxide
      concentration to ensure its biochemical function. A sustained nitric oxide
      releasing scaffold, which supports neuronal cell differentiation, as determined
      by morphometric analysis of neurite outgrowth, is described. Moreover, the effect
      of nitric oxide on the neuroblastoma cell line was also confirmed by
      immunofluorescent analysis of neuronal nuclear protein (NeuN), specific neuronal
      marker and neurofilament (NF) protein, which revealed a significant increase in
      their expression levels, in comparison with undifferentiated cells.

PMID- 29600534
TI  - Effect of Mitomycin C on recurrence of plantar fibromas.
AB  - Although certainly not the first line treatment for plantar fibromas, surgical
      resection is a treatment option for some patients with have failed exhaustive non
      surgical treatment. The use of topical Mitomycin C has been recently shown to
      reduce the recurrence rate of other fibrous lesions. The purpose of this study
      was to determine the impact of topical application of Mitomycin C on recurrence
      rate of plantar fibromas. A retrospective analysis was done from a prospectively
      gathered database with a total 50 consecutive patients over a 16-month study
      period. The control group (n = 29) consisted of patients who underwent only
      surgical resection, while the study group (n = 21) consisted of patients who
      underwent surgical resection with adjuvant therapy using Mitomycin C. The primary
      endpoint was local recurrence after the procedure. Secondary end points included
      complications and toxicity associated with this medication. No patients were lost
      to follow up. Of the 29 patients in the control group, there were 17 patients
      (17/29, 58.6%) had recurrence of the plantar fibroma at a mean follow-up of 9.1
      months. In contrast, in the experimental study group, all patients were free from
      local recurrence. No complications or side effects were associated with Mitomycin
      C use. The results demonstrate that the topical application of Mitomycin C to the
      tumor bed after surgical resection of plantar fibromas reduced the recurrence
      rate. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
      J Orthop Res 36:2554-2561, 2018.

PMID- 29600535
TI  - Nematode-associated microbial taxa do not correlate with host phylogeny,
      geographic region or feeding morphology in marine sediment habitats.
AB  - Studies of host-associated microbes are critical for advancing our understanding
      of ecology and evolution across diverse taxa and ecosystems. Nematode worms are
      ubiquitous across most habitats on earth, yet little is known about host
      associated microbial assemblages within the phylum. Free-living nematodes are
      globally abundant and diverse in marine sediments, with species exhibiting
      distinct buccal cavity (mouth) morphologies that are thought to play an important
      role in feeding ecology and life history strategies. Here, we investigated
      patterns in marine nematode microbiomes, by characterizing host-associated
      microbial taxa in 281 worms isolated from a range of habitat types (deep-sea,
      shallow water, methane seeps, Lophelia coral mounds, kelp holdfasts) across three
      distinct geographic regions (Arctic, Southern California and Gulf of Mexico).
      Microbiome profiles were generated from single worms spanning 33 distinct
      morphological genera, using a two-gene metabarcoding approach to amplify the V4
      region of the 16S ribosomal RNA (rRNA) gene targeting bacteria/archaea and the V1
      V2 region of the 18S rRNA gene targeting microbial eukaryotes. Contrary to our
      expectations, nematode microbiome profiles demonstrated no distinct patterns
      either globally (across depths and ocean basins) or locally (within site);
      prokaryotic and eukaryotic microbial assemblages did not correlate with nematode
      feeding morphology, host phylogeny or morphological identity, ocean region or
      marine habitat type. However, fine-scale analysis of nematode microbiomes
      revealed a variety of novel ecological interactions, including putative parasites
      and symbionts, and potential associations with bacterial/archaeal taxa involved
      in nitrogen and methane cycling. Our results suggest that in marine habitats,
      free-living nematodes may utilize diverse and generalist foraging strategies that
      are not correlated with host genotype or feeding morphology. Furthermore, some
      abiotic factors such as geographic region and habitat type do not appear to play
      an obvious role in structuring host-microbe associations or feeding preferences.

PMID- 29600536
TI  - Copaiba oil enhances in vitro/in vivo cutaneous permeability and in vivo anti
      inflammatory effect of celecoxib.
AB  - OBJECTIVES: The aim of this article was to use copaiba oil (C.O) to improve skin
      permeability and topical anti-inflammatory activity of celecoxib (Cxb). METHODS:
      Formulations containing C.O (1-50%) were associated with Cxb (2%). In vitro skin
      permeability studies were conducted using porcine ear skin. Histological analysis
      of the hairless mice skin samples after application of formulations was achieved
      with the routine haematoxylin/eosin technique. The anti-inflammatory activity was
      assessed using the AA-induced ear oedema mice model. KEY FINDINGS: The
      formulation containing 25% C.O promoted the highest levels of in vitro Cxb
      permeation through pig ear skin, retention in the stratum corneum (SC) and
      epidermis/dermis of pig ear skin in vitro (~5-fold) and hairless mice skin in
      vivo (~2.0-fold), as compared with the control formulation. At 25%, C.O caused SC
      disorganization and increased cell infiltration and induced angiogenesis without
      clear signs of skin irritation. The formulation added to 25% C.O as adjuvant
      inhibited ear oedema and protein extravasation by 77.51 and 89.7%, respectively,
      and that it was, respectively, 2.0- and 3.4-fold more efficient than the
      commercial diethylammonium diclofenac cream gel to suppress these inflammatory
      parameters. CONCLUSIONS: 25% C.O is a potential penetration enhancer for
      lipophilic drugs like Cxb that can improve cutaneous drug penetration and its
      anti-inflammatory activity.

PMID- 29600537
TI  - Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant.
AB  - Hyper-immunoglobulin D syndrome is a rare autosomal-recessive autoinflammatory
      syndrome in which a mevalonate kinase deficiency results due to mutations of the
      mevalonate kinase gene. We report a case of an Asian male infant who was found to
      have hyper-immunoglobulin D syndrome in the absence of fever. His skin
      manifestations included cephalic pustulosis as well recurrent transient and fixed
      pink plaques and nodules on the face and extremities. Subsequent examination
      revealed hyper-immunoglobulin D syndrome with two novel allelic mutations in the
      mevalonate kinase gene: c.895G > A (p.D299N) and c.1168C > T (p.Q390). It is
      important for dermatologists to recognize the varied cutaneous presentations of
      hyper-immunoglobulin D syndrome because rapid diagnosis and treatment can
      significantly affect outcomes.

PMID- 29600538
TI  - SB-216763, a GSK-3beta inhibitor, protects against aldosterone-induced cardiac,
      and renal injury by activating autophagy.
AB  - Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays a
      pivotal role in the pathogenesis of hypertension and renal fibrosis. GSK-3beta
      contributes to inflammatory cardiovascular and renal diseases, but its role in
      Aldo-induced hypertension, and renal damage is not clear. In the present study,
      rats were treated with Aldo combined with SB-216763 (a GSK-3beta inhibitor) for 4
      weeks. Hemodynamic, cardiac, and renal parameters were assayed at the indicated
      time. Here we found that rats treated with Aldo presented cardiac and renal
      hypertrophy and dysfunction. Cardiac and renal expression levels of molecular
      markers attesting inflammation and fibrosis were increased by Aldo infusion,
      whereas the treatment of SB-216763 reversed these alterations. SB-216763
      suppressed cardiac and renal inflammatory cytokines levels (TNF-a, IL-1beta, and
      MCP-1). Meanwhile, SB-216763 increased the protein levels of LC3-II in the
      cardiorenal tissues as well as p62 degradation, indicating that SB-216763 induced
      autophagy activation in cardiac, and renal tissues. Importantly, inhibition of
      autophagy by 3-MA attenuated the role of SB-216763 in inhibiting perivascular
      fibrosis, and tubulointerstitial injury. These data suggest that SB-216763
      protected against Aldo-induced cardiac and renal injury by activating autophagy,
      and might be a therapeutic option for salt-sensitive hypertension and renal
      fibrosis.

PMID- 29600539
TI  - Solvent composition dependent signal reduction of molecular ions generated from
      aromatic compounds in (+) atmospheric pressure photoionization mass spectrometry.
AB  - RATIONALE: The ionization process is essential for successful mass spectrometric
      (MS) analysis because of its influence on selectivity and sensitivity. In
      particular, certain solvents reduce the ionization of the analyte, thereby
      reducing the overall sensitivity in atmospheric pressure photoionization (APPI).
      Since the sensitivity varies greatly depending on the solvents, a fundamental
      understanding of the mechanism is required. METHODS: Standard solutions were
      analyzed using a (+)-APPI Q Exactive ion trap mass spectrometer (Thermo
      Scientific). Each solution was infused directly into the APPI source at a flow
      rate of 100 MUL/min and the APPI source temperature was 300 degrees C. Other
      operating mass spectrometric parameters were maintained under the same
      conditions. Quantum mechanical calculations were carried out using the Gaussian
      09 suite program. RESULTS: Density functional theory was used to calculate the
      reaction enthalpies (?H) of the reactions between toluene and other solvents. The
      experimental and theoretical results showed good agreement. The abundances of
      analyte ions were well correlated with the calculated ?H values. Therefore, the
      results strongly support the suggested signal reduction mechanism. In addition,
      linear correlations between the abundance of toluene and analyte molecular ions
      were observed, which also supports the suggested mechanism. CONCLUSIONS: A
      solvent composition dependent signal reduction mechanism was suggested and
      evaluated for the (+)-APPI-MS analysis of polyaromatic hydrocarbons (PAHs)
      generating mainly molecular ions. Overall, the evidence provided in this work
      suggests that reactions between solvent cluster(s) and toluene molecular ions are
      responsible for the observed reductions in signal.

PMID- 29600541
TI  - Human Enzymes for Organic Synthesis.
AB  - Human enzymes have been widely studied in various disciplines. The number of
      reactions taking place in the human body is vast, and so is the number of
      potential catalysts for synthesis. Herein, we focus on the application of human
      enzymes that catalyze chemical reactions in course of the metabolism of drugs and
      xenobiotics. Some of these reactions have been explored on the preparative scale.
      The major field of application of human enzymes is currently drug development,
      where they are applied for the synthesis of drug metabolites.

PMID- 29600542
TI  - A new 2% testosterone gel formulation: a comparison with currently available
      topical preparations.
AB  - Testosterone gel formulations have become a popular testosterone replacement
      therapy in patients with hypogonadism since their advent in the year 2000. The
      gel formulations restore testosterone levels to mid-normal physiological levels
      (14-17.5 nmol/L) as early as within 24 h, and help alleviate the signs and
      symptoms of testosterone deficiency, thereby leading to an improved quality of
      life. Although testosterone gels have a favourable efficacy and safety profile as
      compared to injectable and patch formulations, risk of secondary exposure poses a
      challenge. Approved testosterone topical formulations include Tostrex(r)
      (Tostran(r) , Fortesta(r) ), Androgel(r) (Testogel(r) ), Testim(r) and Axiron(r)
      (solution), which have a favourable efficacy profile and positively impacted
      patient-reported outcome(s). Besides, Testavan, which is a 2% testosterone gel,
      is under registration in Europe and already approved in Australia in May 2017.
      Testavan uses a novel hydroalcoholic and highly viscous topical formulation. This
      product comes with a metered dose dispenser and a cap applicator that allows a
      hands-free application for precise dispensing and application. The present
      article provides a comprehensive review of pharmacokinetic, tolerability and
      safety profile of the testosterone gels available in the market along with the
      new 2% testosterone gel, Testavan.

PMID- 29600543
TI  - Speckle tracking analysis in intensive care unit: A toy or a tool?
AB  - The use of conventional echocardiography in the intensive care unit (ICU) is
      today established to assess left and right ventricular systolic function, for
      preload determination and procedural guidance. Next step in ICU echocardiography
      could be the use of novel ultrasound techniques such as strain echocardiography
      to assist in the management of patients with acute coronary syndrome, heart
      failure, or pulmonary embolism. This review has gathered the available evidence
      supporting the incremental value of strain in the diagnostic workup of cardiac
      diseases treated in ICU.

PMID- 29600545
TI  - Strategies to support pressure injury best practices by the inter-professional
      team: A systematic review.
AB  - Optimal pressure injury (ulcer) management by the inter-professional team
      requires appropriate health care system and organisational resources,
      infrastructure, and policies. A systematic review was conducted on pressure
      injury care-related education and health care system-/organisation-level
      strategies. A search for relevant articles published between January 2006 and
      October 2014 was applied to 8 databases. Ultimately, 22 articles pertaining to
      education and training and 12 articles pertaining to health care system and
      organisation supports for pressure injury care were included in the systematic
      review. A lack of pressure injury assessment and management knowledge by health
      care professionals was an overriding theme in the education literature. Some of
      the methods preferred for pressure injury education among nurses and physicians
      included information technology (eg, e-learning) with technology support and the
      use of high-quality wound pictures. Although the evidence is scarce, the
      literature did highlight specific system- and organisation-level barriers and
      enablers that influence practice change, including inter-professional
      communication and human resource investments. In conclusion, (1) the current
      evidence on the education and system-level enablers, barriers, and strategies to
      optimise pressure injury best practices requires further investigation, and (2)
      multi-faceted, up-stream, evidence-based approaches for pressure injury care are
      essential to improve health care and patient-related outcomes.

PMID- 29600544
TI  - Down-regulated long non-coding RNA ANRIL restores the learning and memory
      abilities and rescues hippocampal pyramidal neurons from apoptosis in
      streptozotocin-induced diabetic rats via the NF-kappaB signaling pathway.
AB  - Diabetes often causes learning and memory deficits, which leads to unfavorable
      behavioral performance. In this study, we investigated the effects of long non
      coding RNA (lncRNA) ANRIL on learning, memory abilities, and hippocampal neuronal
      apoptosis via the NF-kappaB signaling pathway in streptozotocin (STZ)-induced
      diabetic rats. After successful establishment of diabetic rat models, the
      subjects were then assigned into the DM, DM + si-ANRIL, DM + si-negative control
      (si-NC) groups, as well as an additional normal group. Morris water maze test was
      employed to assess behavioral performance of rats, followed by the recording of
      body weight and blood glucose levels. Expressions of ANRIL, NF-kappaB signaling
      pathway-related, and apoptosis-related genes were examined by qRT-PCR and western
      blotting. Rat hippocampus expression levels of cleaved-caspase-3 were determined
      by immunofluorescence. Cell apoptosis was examined by TUNEL assay. Versus to the
      normal group, revealed there to be activation of the NF-kappaB signaling pathway,
      decreased weight, increased blood glucose, increased escape latency, reduced
      residence time, memory impairment, increased cleaved-caspase-3 expression, and
      increased apoptosis were detected in the DM and DM + si-NC groups. The DM + si
      ANRIL group exhibited inhibited NF-kappaB signaling pathway, weight loss,
      decreased blood glucose, recovered memory, decreased cleaved-caspase-3 expression
      and reduced apoptosis compared to the DM group, with higher weight of rats, lower
      blood glucose levels, and stronger memory abilities in the DM + si-ANRIL group.
      Taken together, these findings indicate that silencing lncRNA ANRIL promotes
      memory recovery and decreases hippocampal neurons apoptosis in diabetic rats
      through the inhibition of the NF-kappaB signaling pathway.

PMID- 29600547
TI  - The CANMAT guidelines for bipolar disorder.

PMID- 29600540
TI  - Mechanisms of Wnt signaling and control.
AB  - The Wnt signaling pathway is a highly conserved system that regulates complex
      biological processes across all metazoan species. At the cellular level, secreted
      Wnt proteins serve to break symmetry and provide cells with positional
      information that is critical to the patterning of the entire body plan. At the
      organismal level, Wnt signals are employed to orchestrate fundamental
      developmental processes, including the specification of the anterior-posterior
      body axis, induction of the primitive streak and ensuing gastrulation movements,
      and the generation of cell and tissue diversity. Wnt functions extend into
      adulthood where they regulate stem cell behavior, tissue homeostasis, and damage
      repair. Disruption of Wnt signaling activity during embryonic development or in
      adults results in a spectrum of abnormalities and diseases, including cancer. The
      molecular mechanisms that underlie the myriad of Wnt-regulated biological effects
      have been the subject of intense research for over three decades. This review is
      intended to summarize our current understanding of how Wnt signals are generated
      and interpreted. This article is categorized under: Biological Mechanisms > Cell
      Signaling Developmental Biology > Stem Cell Biology and Regeneration.

PMID- 29600546
TI  - Cooperative Catalysis with Coupled Chiral Induction in 1,3-Dipolar Cycloadditions
      of Azomethine Ylides.
AB  - 1,3-Dipolar cycloadditions (1,3-DC) between imino esters (as precursors of N
      metallated azomethine ylides) and pi-deficient alkenes are promoted by
      cooperative asymmetric Lewis acid/Bronsted base catalysis. The components of
      these catalytic pairs are silver salts derived from enantiopure commercially
      available BINOL-based phosphoric acids and Cinchona alkaloids. Chiral phosphoric
      silver(I) salts promote HOMO raising of in situ formed 1,3-dipoles, whereas
      protonated cinchona alkaloids generate a LUMO lowering for the dipolarophiles
      resulting in a global acceleration of the 1,3-DC. The best results were obtained
      with BINOL-derived silver phosphate and hydrocinchonine. Matching between both
      cooperative metallo- and organocatalyst results in an enhanced enantiomeric
      excess, superior to that reached by both separate components. NOESY experiments
      and DFT calculations are compatible with a non-covalent interaction (hydrogen
      bond) between both catalysts, which results in close contacts and mutually
      coupled chiral environments.

PMID- 29600548
TI  - Acute invasive fungal rhinosinusitis in twenty-one diabetic patients.

PMID- 29600549
TI  - Phenotypes, genotypes, and the management of paroxysmal movement disorders.
AB  - : As a consequence of the genomic revolution, a large number of publications
      describing paroxysmal movement disorders have been published in the last few
      years, shedding light on their molecular pathology. Routine gene testing is not
      necessary to guide treatment for typical forms of paroxysmal kinesigenic
      dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and episodic
      ataxia type 1 or 2. It can, however, be helpful in the management of atypical or
      complex cases, especially for genetic counselling, treatment strategies, and the
      offer of preimplantation genetic diagnosis. Antiepileptic drugs remain the
      treatment of choice for PKD and episodic ataxia type 1, benzodiazepines are often
      useful for PNKD, and episodic ataxia type 2 benefits from acetazolamide
      regardless of the genetic etiology. WHAT THE PAPER ADDS: A growing number of
      genes have been associated with classic and newly described paroxysmal movement
      disorders. Paroxysmal movement disorders share common mechanisms and clinical
      features with other neurological paroxysmal phenomena including epilepsy and
      migraine.

PMID- 29600550
TI  - Assessment of multidirectional movements of the common carotid artery in
      atherothrombotic stroke using dimensional speckle tracking carotid
      ultrasonography: A prospective, controlled cohort study.
AB  - AIM: We aimed to explore the relevance of multidirectional movements of the
      common carotid artery in atherothrombotic stroke. METHODS AND RESULTS: We
      prospectively enrolled 69 patients with atherothrombotic stroke (stroke group)
      and 69 age-matched and sex-matched controls (control group) who underwent carotid
      ultrasonography. Based on the speckle tracking technique, circumferential and
      radial movements of the common carotid artery were analyzed from transverse and
      longitudinal B-mode images of the common carotid artery. Peak longitudinal and
      radial displacements, strain, and strain rate were measured. Mean age of the
      overall population was 64 +/- 11 years, and 57% (78 patients) were men. In the
      transverse image, circumferential strain was significantly lower in the stroke
      group than in the control group (5.6 +/- 1.6 vs 4.2 +/- 1.7, P < .001). In
      multivariate logistic regression analysis, circumferential strain was
      independently associated with stroke (odds ratio: 0.60, P = .001). Compared with
      conventional risk factors, as well as carotid intima-media thickness and carotid
      plaque, the addition of a strain parameter appeared to improve discrimination of
      a stroke event (area under the receiver operating characteristic curve: 0.65 and
      0.75 vs 0.84, respectively; P < .05 for both). CONCLUSIONS: Circumferential
      strain of the common carotid artery might serve as a novel surrogate marker of
      atherothrombotic stroke. Multidirectional strain imaging of the common carotid
      artery may provide more information than conventional carotid ultrasonography and
      identify clinical risk factors for risk stratification of an acute stroke event.

PMID- 29600551
TI  - Hand distance modulates the electrophysiological correlates of target selection
      during a tactile search task.
AB  - This study investigated whether the N140cc ERP component, described as a possible
      electrophysiological marker of target selection in touch, was modulated by body
      posture. Participants performed a tactile search task in which they had to
      localize a tactile target, presented to the left or right hand, while a
      simultaneous distractor was delivered to the opposite hand. Importantly, the
      distance between target and distractor (hands separation) was manipulated in
      different experimental conditions (near vs. far hands). Results showed reduced
      errors and enhanced amplitudes of the late N140cc when the hands were far apart
      than in close proximity. This suggests that the competition between target and
      distractor is stronger when the hands are close together in the near condition,
      resulting in a degraded selection process. These findings confirm that the N140cc
      reflects target selection during the simultaneous presentation of competing
      stimuli and demonstrate for the first time that the attentional mechanisms
      indexed by this ERP component are based at least in part on postural
      representations of the body.

PMID- 29600552
TI  - Health-seeking experience of North Korean women defectors in South Korea.
AB  - OBJECTIVE(S): The objective of the study was to explore and describe the health
      seeking experience of North Korean women defectors settled in South Korea. DESIGN
      AND SAMPLE: A qualitative study was conducted using Colaizzi's phenomenological
      method. Participants were 10 North Korean women defectors. MEASURES: Data were
      collected through in-depth, unstructured interviews with individual participants.
      RESULTS: A total of 24 themes, eight theme clusters, and four categories emerged.
      The structure of the health-seeking experience for them was identified as 'having
      new opportunities to better understand my own body and protecting my own health
      while adapting to the health care system of the South'. The four categories were:
      finding out about my own body, confusion regarding the medical treatment,
      enjoying the health care benefits, and protecting my own health. CONCLUSIONS: The
      findings of this study will help improve the understanding of the health-seeking
      experience of North Korean women defectors and provide valuable resources to
      assist in caring for their health needs. This will contribute to preparing the
      groundwork to enhance the quality of their remaining life in South Korea.

PMID- 29600553
TI  - A multiple mediator analysis approach to quantify the effects of the ADH1B and
      ALDH2 genes on hepatocellular carcinoma risk.
AB  - Previous work suggested a genetic component affecting the risk of hepatocellular
      carcinoma (HCC) and mediation analyses have elucidated potential indirect
      pathways of these genetic effects. Specifically, the effects of alcohol
      dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes on HCC risk vary
      based on alcohol consumption habits. However, alcohol consumption may not be the
      only mediator in the identified pathway: factors related to alcohol consumption
      may contribute to the same indirect pathway. Thus, we developed a multimediator
      model to quantify the genetic effects on HCC risk through sequential dichotomous
      mediators under the counterfactual framework. Our method provided a closed form
      formula for the mediation effects through different indirect paths, which
      requires no assumption for the rarity of outcome. In simulation studies of a
      finite sample, we presented the utility of the method with the variance of the
      effects estimated using the delta method and bootstrapping. We applied our method
      to data from participants in Taiwan (580 cases and 3,207 controls) and quantified
      the mediation effects of single nucleotide polymorphisms (SNPs) in the ADH1B and
      ALDH2 genes on HCC through alcohol consumption (yes/no) and high alanine
      transaminase (ALT) levels (greater than or equal to 45 U/L or below 45 U/L).
      Assuming a dominant risk model, we identified that the SNPs' effects through
      alcohol consumption is more significant than through ALT levels on HCC risk. This
      new method provides insight to the magnitude of various casual mechanisms as a
      closed form solution and can be readily applied in other genomic studies.

PMID- 29600554
TI  - Preparation and evaluation of open-tubular capillary column combining a metal
      organic framework and a brush-shaped polymer for liquid chromatography.
AB  - In this work, an open-tubular capillary liquid-phase column was prepared by
      modifying chain polymer on the inner surface of capillary and chemical bonding of
      metal organic frameworks, NH2 -UiO-66, to the brushes of chain polymer
      (poly(glycidyl methacrylate)). Besides advantages of facial preparation and good
      permeability, the chain polymer effectively increases the modification amount of
      NH2 -UiO-66 nanoparticles to increase the phase ratio of open-tubular capillary
      column and enhance the interactions with analytes. The results of scanning
      electron microscope energy-dispersive X-ray spectra indicated that NH2 -UiO-66
      nanoparticles were successfully bonded to the chain polymer. Because of the
      hydrophobic interaction and hydrogen bonding interaction between the analytes and
      the ligand of NH2 -UiO-66, different analytes were well separated on the NH2 -UiO
      66-modified poly(glycidyl methacrylate) capillary (1.12 m * 25 MUm id * 365 MUm
      od) with the high absolute column efficiency reaching 121 477 plates, benefiting
      from an open-tubular column and low mass transfer resistance provided by polymer
      brush and metal-organic framework crystal. The relative standard deviations of
      the retention time for run-to-run, day-to-day, and column-to-column (n = 3) runs
      are below 4.28%, exhibiting good repeatability. Finally, the column was
      successfully applied to separation of flavonoids in licorice.

PMID- 29600555
TI  - Right atrial structure and function in patients with hypertension and with
      chronic heart failure.
AB  - BACKGROUND: Prior studies have shown that both heart failure (HF) and atrial
      fibrillation (AF) are factors that impact left atrial function and structure.
      However, right atrial (RA) function measured as RA emptying fraction (RAEF) on
      echocardiography has not been analyzed systematically in a chronic HF population.
      The aim of this study was to assess RA volume index (RAVI) and RAEF in patients
      with chronic HF and patients with hypertension (HTN) and to relate these findings
      to other cardiopulmonary ultrasound parameters and 12-month outcomes. METHODS AND
      RESULTS: In this prospective observational study, we identified 119 patients with
      chronic HF (64 patients without a history of AF [HF without AF], 55 with AF [HF
      with AF]), and 127 patients with HTN but without important cardiac disease who
      underwent routine outpatient transthoracic echocardiography. We found that RAEF
      was impaired in patients with HF without AF compared to patients with HTN (35% +/
      2 vs 50% +/-1, P < .001), whereas RAVI did not differ between these two groups.
      Lower RAEF was associated with larger RAVI and higher estimated RA pressures but
      not with a higher degree of pulmonary congestion by lung ultrasound. Both lower
      RAEF and higher RAVI were associated with an increased risk of 12-month HF
      hospitalizations or all-cause death (age, sex, and AF adjusted HR: 4.07, 95% CI:
      1.69-9.79; P = .002, vs 2.74, 95% CI: 1.15-6.54, P = .023). CONCLUSIONS: In an
      outpatient HF cohort, both lower RAEF and increased RAVI were associated with
      other markers of impaired cardiac function and 12-month adverse events.

PMID- 29600557
TI  - Corrigendum.

PMID- 29600556
TI  - 3D bone models to study the complex physical and cellular interactions between
      tumor and the bone microenvironment.
AB  - As the complexity of interactions between tumor and its microenvironment has
      become more evident, a critical need to engineer in vitro models that veritably
      recapitulate the 3D microenvironment and relevant cell populations has arisen.
      This need has caused many groups to move away from the traditional 2D, tissue
      culture plastic paradigms in favor of 3D models with materials that more closely
      replicate the in vivo milieu. Creating these 3D models remains a difficult
      endeavor for hard and soft tissues alike as the selection of materials,
      fabrication processes, and optimal conditions for supporting multiple cell
      populations makes model development a nontrivial task. Bone tissue in particular
      is uniquely difficult to model in part because of the limited availability of
      materials that can accurately capture bone rigidity and architecture, and also
      due to the dependence of both bone and tumor cell behavior on mechanical
      signaling. Additionally, the bone is a complex cellular microenvironment with
      multiple cell types present, including relatively immature, pluripotent cells in
      the bone marrow. This prospect will focus on the current 3D models in development
      to more accurately replicate the bone microenvironment, which will help
      facilitate improved understanding of bone turnover, tumor-bone interactions, and
      drug response. These studies have demonstrated the importance of accurately
      modelling the bone microenvironment in order to fully understand signaling and
      drug response, and the significant effects that model properties such as
      architecture, rigidity, and dynamic mechanical factors have on tumor and bone
      cell response.

PMID- 29600558
TI  - When elephants fall asleep: A literature review on elephant rest with case
      studies on elephant falling bouts, and practical solutions for zoo elephants.
AB  - Little attention has been paid to the resting and sleeping behavior of zoo
      elephants so far. An important concern is when elephants avoid lying down, due to
      degenerative joint and foot disease, social structure, or stressful environmental
      changes. Inability or unwillingness to lie down for resting is an important
      welfare issue, as it may impair sleep. We emphasize the importance of satisfying
      rest in elephants by reviewing the literature on resting behavior in elephants
      (Loxodonta africana and Elephas maximus) as well as the documentation of four
      cases from European zoos and our own direct observations in a zoo group of four
      female African elephants during 12 entire days. The common denominator in the
      case reports is the occurrence of a falling bout out of a standing position
      subsequently to a cessation of lying rest for different periods of time. Although
      well-known in horses as "episodic collapse" or "excessive drowsiness," this
      syndrome has not been described in elephants before. To enable its detection, we
      recommend nocturnal video monitoring for elephant-keeping institutions. The
      literature evaluation as well as own observational data suggest an inverse
      relationship between lying rest and standing rest. Preventative measures consist
      of enclosure modifications that facilitate lying rest (e.g., sand hills) or
      standing rest in a leaning position as a substitute. Anecdotal observations
      suggest that the provision of appropriate horizontal environmental structures may
      encourage safe, sleep-conducive standing rest. We provide drawings on how to
      install such structures. Effects of providing such structures should be evaluated
      in the future.

PMID- 29600559
TI  - Altering Neurospora crassa MOB2A exposes its functions in development and affects
      its interaction with the NDR kinase COT1.
AB  - The Neurospora crassa Mps One Binder (MOB) proteins MOB2A and MOB2B physically
      interact with the Nuclear Dbf2 Related (NDR) kinase COT1 and have been shown to
      have overlapping functions in various aspects of asexual development. Here, we
      identified two N. crassa MOB2A residues, Tyr117 and Tyr119, which are potentially
      phosphorylated. Using phosphomimetic mob-2a mutants we have been able to
      establish that apart from their previously described roles, MOB2A/B are involved
      in additional developmental processes. Enhanced conidial germination, accompanied
      by conidial agglutination, in the phosphomimetic mutants indicated that MOB2A is
      a negative regulator of germination. Thick-section imaging of perithecia revealed
      slow maturation and a lack of asci alignment in the mutant strains demonstrating
      a role for MOB2A in sexual development. We demonstrate that even though MOB2A and
      MOB2B have some overlapping functions, MOB2B cannot compensate for the roles
      MOB2A has in conidiation and germination. Altering Tyr residues 117 and 119
      impaired the physical interactions between MOB2A and COT1, most likely
      contributing to some of the observed effects. As cot-1 and the phosphomimetic
      mutants share an extragenic suppressor (gul-1), we concluded that at least some
      of the effects imposed by altering Tyr117 and Tyr119 are mediated by the NDR
      kinase.

PMID- 29600560
TI  - Contact sensitivity in patients with venous leg ulcer: A multi-centric Indian
      study.
AB  - Venous leg ulcers are the most common form of non-healing leg ulcers. They are
      subjected to treatments such as topical medications, dressings, and compression
      therapies. This can lead to exposure to a number of allergens with subsequent
      sensitisation and contact dermatitis of the regional skin. This may contribute to
      the poor ulcer healing. To detect the various contact sensitisers in patients
      with venous leg ulcers through patch testing, patients from 6 centres across
      India with venous leg ulcers of longer than 6 weeks duration were enrolled for
      the study. They were patch tested using a special parch test kit with 27
      antigens. A total of 172 patients were included in the study; 82 (48.2%) tested
      positive for at least 1 antigen. Among them, polyvalent sensitisation was noted
      in 71% of patients. Wood tar mix (10.4%) and the framycetin (8.7%) were the most
      common allergens. There is a high frequency of allergic sensitisation to various
      ingredients of topical therapies used in the venous ulcer management, which may
      interfere with wound healing. Avoiding them can help obtain a better therapeutic
      outcome.

PMID- 29600561
TI  - Relationships between vital rates and ecological traits in an avian community.
AB  - Comparative studies about the relationships between vital rates and ecological
      traits at the community level are conspicuously lacking for most taxa because
      estimating vital rates requires detailed demographic data. Identifying
      relationships between vital rates and ecological traits could help to better
      understand ecological and evolutionary demographic mechanisms that lead to
      interspecific differences in vital rates. We use novel dynamic N-mixture models
      for counts to achieve this for a whole avian community comprising 53 passerine
      species, while simultaneously accounting for density dependence and environmental
      stochasticity in recruitment and survival and, importantly, correcting our
      inferences for imperfect detection. Demographic stochasticity is taken into
      account in the form of the binomial and Poisson distributions describing survival
      events and number of recruits. We then explore relationships between estimated
      demographic parameters (i.e., vital rates) and ecological traits related to
      migration patterns, diet, habitat and nesting location of each species. The
      relative importance of recruitment and adult survival as contributors to
      population growth varied greatly among species, and interspecific differences in
      vital rates partly reflected differences in ecological traits. Migratory mode was
      associated with interspecific differences in population growth and density
      dependence. Resident species had higher population growth rates than long- and
      short-distance migrants. We found no relationships between diet and population
      growth rate. Habitat differences were associated with different growth rates:
      alpine, wetland and farmland species had lower population growth rates than
      forest species. Differences in population growth rates among nesting locations
      showed that breeding habitat is essential for population dynamics. Our study
      reveals relationships between ecological traits and contributions of vital rates
      to population growth and suggests ways in which patterns of population growth
      fluctuations in a community might be determined by life history.

PMID- 29600562
TI  - Serum level of endostatin and digital ulcers in systemic sclerosis patients.
AB  - Patients with systemic sclerosis (SSc) are at a high risk of the development of
      ischaemic digital ulcers (DUs) that can be complicated with infections, gangrene,
      and osteomyelitis. The aim of this study is to evaluate the role of endostatin in
      scleroderma DUs.In total, 90 SSc patients were enrolled in this study. Serum
      endostatin levels and DU assessment were determined in all SSc patients. The
      serum levels of endostatin significantly increased with progression of
      capillaroscopic damage (P < .01). The serum levels of endostatin are
      significantly (P < .05) higher in SSc patients with new DUs than in SSc patients
      without new DUs (127 +/- 31.1 ng/mL vs 116.3 +/- 39.7 ng/mL). The Receiver
      Operating Characteristic (ROC) curves demonstrated good accuracy of new DU
      prediction for the serum level of endostatin (0.70, P < .01 [95% confidence
      interval (CI) 0.59-0.81]). Using a cut-off value of 116 ng/mL, the odds ratio was
      2.609 (CI 1.075-6.330, P < .05). The serum levels of endostatin are significantly
      (P < .01) higher in SSc patients with infected DUs than in SSc patients without
      infected DUs (139.2 [114.6-340.91] ng/mL vs 117.5 [64.3-163.9] ng/mL). Serum
      levels of endostatin are higher in patients with DUs, especially in those with
      infected DUs.

PMID- 29600563
TI  - Alendronate induces osteoclast precursor apoptosis via peroxisomal dysfunction
      mediated ER stress.
AB  - Nitrogen-containing bisphosphonates including alendronate (ALN) are the current
      first line antiresorptive drug in treating osteoporosis. In our study, we found
      that ALN administration impaired the secretion of platelet derived growth factor
      BB (PDGF-BB), the most important angiogenic cytokines produced by preosteoclast
      (POC), in both sham and ovariectomized (OVX) mice. To further understand this
      phenomenon, we induced bone marrow macrophages (BMMs) to POCs in vitro and
      detected the effects of ALN particularly in POCs. The proapoptotic effect of ALN
      in POCs was confirmed by flow cytometry. On the molecular level, we found that
      farnesyl diphosphate synthase (FDPS) inhibition of ALN led to peroxisomal
      dysfunction and up regulation of cytoprotective protein glucose-regulated protein
      (GRP) 78. Peroxisomal dysfunction further induced endoplasmic reticulum (ER)
      stress in POCs and finally resulted in cell apoptosis marked by reduced
      expression of B-cell lymphoma 2 (Bcl-2) and increased expressions of
      CCAAT/enhancer binding protein homologous protein (CHOP), Bcl2 associated X
      (Bax), and cleaved caspase-3. We concluded that ALN has no selectivity in
      inhibiting POC and mature osteoclast. For POCs, ALN inhibition of FDPS leads to
      peroxisomal dysfunction, which further mediates ER stress and finally causes cell
      apoptosis. Considering that decreased angiogenesis is also an important issue in
      treating osteoporosis, how to preserve pro-angiogenic POCs while depleting mature
      osteoclasts is a problem worthy to be solved.

PMID- 29600564
TI  - Statistical analysis of factors affecting re-operative times in paediatric
      patients with scar deformity after deep second-degree burn injury.
AB  - Deep second-degree burn injuries pose a challenge for treating scar deformity in
      developing paediatric patients. Some patients underwent several re-operations
      during their development. There was no literature reporting which factors affect
      re-operative times. In this article, we intend to analyse possible influential
      factors that are responsible for re-operative times in paediatric patients with
      scar deformity after deep second-degree burn injuries. From 2010 to 2016, 177
      paediatric cases with a history of deep second-degree burn injury who underwent
      re-operation once, twice, and equal to or more than thrice were recruited to this
      study, with age ranging from 0 to 18 years. The following factors were analysed:
      age, gender, size of scar, method for reconstruction, location, postoperative
      anti-scar treatment, preschool group, school group, combined deformity, and
      combined method for reconstruction. One-way ANOVA and multi-way ANOVA analysis
      were used as statistical tools to analyse the above factors and re-operative
      times. There were 83 male cases and 94 female cases, with an average age of 7.47
      years. Statistical significance was achieved for the size of scar (P = 0.000),
      operation method (P = 0.001), and combined deformity (P = 0.026) under 1-way
      ANOVA in different re-operative times. The operation methods for the head and
      neck area (P < 0.05) and the lower extremities (P < 0.05) are critical factors
      for multi-factor variance analysis in different re-operative times. Multivariate
      logistic regression analysis also demonstrated that the size of scar was an
      independent risk factor for the number of operations. Combined operative method
      was a protective risk factor for the number of operations. There was no
      statistical significance obtained for other factors. Size of scar, operation
      method, and combined operation method are the risk factors for re-operative
      times, while operation methods for the head and neck area and lower extremities
      are the critical factors for re-operative times. We can use the combined method
      to resolve scar-related problems in order to reduce re-operative times.

PMID- 29600565
TI  - Recent research on stimulated emission depletion microscopy for reducing
      photobleaching.
AB  - Stimulated emission depletion (STED) microscopy is a useful tool in investigation
      for super-resolution realm. By silencing the peripheral fluorophores of the
      excited spot, leaving only the very centre zone vigorous for fluorescence, the
      effective point spread function (PSF) could be immensely squeezed and subcellular
      structures, such as organelles, become discernable. Nevertheless, because of the
      low cross-section of stimulated emission and the short fluorescence lifetime, the
      depletion power density has to be extremely higher than the excitation power
      density and molecules are exposed in high risk of photobleaching. The existence
      of photobleaching greatly limits the research of STED in achieving higher
      resolution and more delicate imaging quality, as well as long-term and dynamic
      observation. Since the first experimental implementation of STED microscopy,
      researchers have lift out variety of methods and techniques to alleviate the
      problem. This paper would present some researches via conventional methods which
      have been explored and utilised relatively thoroughly, such as fast scanning,
      time-gating, two-photon excitation (TPE), triplet relaxation (T-Rex) and
      background suppression. Alternatively, several up-to-date techniques, especially
      adaptive illumination, would also be unveiled for discussion in this paper. The
      contrast and discussion of these modalities would play an important role in
      ameliorating the research of STED microscopy.

PMID- 29600566
TI  - Endothelial committed oral stem cells as modelling in the relationship between
      periodontal and cardiovascular disease.
AB  - In the present study we have mimicked, in vitro, an inflammatory process using
      Lipopolysaccharide derived from Porphyromonas Gingivalis (LPS-G) and human
      Periodontal Ligament Stem Cells induced to endothelial differentiation (e
      hPDLSCs). The research project has been organized into the three following steps:
      i) induction of hPDLSCs toward endothelial differentiation; ii) evaluation of the
      molecular signaling pathway involved in the response to the LPS-G, and iii)
      functional response evaluation of the living construct constituted by porcine
      decellularized valve/e-hPDLSCs treated with LPS-G. Obtained results showed that 5
      MUg/ml LPS-G stimulus provokes: a slowdown of cell growth starting from 24 hr and
      the release of IL6, IL8, and MCP1 molecules. Signaling network analyzed showed
      the activation of TLR4/ NFkB/ERK1/2/p-ERK1/2 signaling mediated by MyD88 in LPS-G
      stimulated e-hPDLSCs, moreover a time course put in evidence a nuclear
      traslocation of ERK1/2 and p-ERK1/2 in differentiated samples. Following, the
      ability of e-hPDLSCs to expand and colonize the decellularized porcine heart
      valves was appraised at ultrastructural level. Considering that, the Reactive
      Oxygen Species (ROS) play an important role in the progression and development of
      cardiovascular disease (CVD), in LPS-G living construct model e
      hPDLSCs/decellularized porcine heart valves (dPHV), ROS production was assessed.
      Time lapse experiments evidenced that LPS-G provokes in e-hPDLSCs a rapid and
      sustained increase in ROS generation, negligible on undifferentiated cells. From
      obtained data, by multiparametric analyses, a reasonable conclusion may be that
      the inflammation process activated by LPS-G can affect endothelial cells and
      could represent in vivo a possible pathological and predictor state of CVD.

PMID- 29600567
TI  - Cultural Heritage Studies with Mobile NMR.
AB  - Nuclear magnetic resonance (NMR) provides in situ information about selected
      isotope densities in samples and objects, while also providing contrast through
      rotational and translational molecular dynamics. These parameters are probed not
      only in NMR spectroscopy and imaging but also in nondestructive materials testing
      by mobile stray-field NMR, the unique properties of which are valuable in
      cultural heritage studies. We present recent progress in the analysis of cultural
      heritage with mobile 1 H NMR stray-field sensors, for which the detection zone is
      outside of the NMR magnet. Prominent applications include the analysis of
      stratigraphies in paintings and frescoes, and the assessment of material states
      changing under the impact of aging, conservation, and restoration.

PMID- 29600568
TI  - 'Look mommy, I'm eating the plate model!' Biopedagogies and coping with obesity
      through objectification.
AB  - Childhood obesity is increasing in many parts of the world. For the child,
      obesity often involves major social challenges. Within the framework of social
      studies of children and childhood and employing the concept of biopedagogies, I
      explore how children with severe obesity who participate in a long-term
      rehabilitation programme changed the perception of their bodies from 'being fat'
      to 'suffering from obesity' by embracing the biopedagogies involved. Due to this
      transformation, 'obesity' was made into an entity - 'a thing' that the children
      could work on -, which was used for coping and change. The article is based on an
      ethnographic field study of a Norwegian randomized medical intervention trial for
      children with obesity. A virtual abstract of this paper can be viewed at:
      https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA.

PMID- 29600569
TI  - Characterization of the Actinonin Biosynthetic Gene Cluster.
AB  - The hydroxamate moiety of the natural product actinonin mediates inhibition of
      metalloproteinases because of its chelating properties towards divalent cations
      in the active site of those enzymes. Owing to its antimicrobial activity,
      actinonin has served as a lead compound for the development of new antibiotic
      drug candidates. Recently, we identified a putative gene cluster for the
      biosynthesis of actinonin. Here, we confirm and characterize this cluster by
      heterologous pathway expression and gene-deletion experiments. We assigned the
      biosynthetic gene cluster to actinonin production and determine the cluster
      boundaries. Furthermore, we establish that ActI, an AurF-like oxygenase, is
      responsible for the N-hydroxylation reaction that forms the hydroxamate warhead.
      Our findings provide the basis for more detailed investigations of actinonin
      biosynthesis.

PMID- 29600570
TI  - Medical communication: the views of simulated patients.
AB  - CONTEXT: Simulated patients (SPs) are extensively used in the teaching of medical
      communication, both for students and doctors. They occupy a unique middle ground
      between patients and physicians: although free from the prejudices that medical
      training brings, they work closely with clinical tutors to promote the principles
      of patient-centred consulting. Despite this, there is relatively little research
      around their views on what makes for good communication practice. This study aims
      to address this gap in the literature through a qualitative analysis of SPs'
      opinions, especially in the context of medical student communication. METHODS:
      Eighteen SPs from two medical schools, Hull York Medical School and Durham, were
      interviewed, using an in-depth, one-to-one, semi-structured approach. Data,
      transcribed verbatim, were thematically analysed. RESULTS: Three global themes
      were identified: (i) listening and empathy and showing it, (ii) continual human
      connection and (iii) information flow from the patient. These three themes,
      termed the communication triad, form a type of virtuous circle, each facilitating
      the other. Listening and empathy were facilitated through attributes, including
      attentive non-verbal communication, and through responding to cues, including
      making effective empathetic statements. Continual human connection was
      facilitated through successful beginnings, including preferring open questions to
      'robotic' tick-list questions and allowing patients time to have their say.
      Mirroring, professional appearance, appropriate physical contact and a human
      approach were amongst other factors facilitating connection with patients.
      Information flow was encouraged by factors including showing an interest in the
      patient and use of silence; flow was curtailed by undesirable attributes,
      including interrupting, dismissive communication and making assumptions about
      aspects such as sexuality. CONCLUSION: This first in-depth study of SPs' views on
      medical consulting identifies a communication triad that both affirms and builds
      on the current literature base. Five novel teaching points emerge, with clear
      relevance for best practice communication teaching and curricula design.

PMID- 29600571
TI  - Acute aortic regurgitation following fibrous strand rupture of aortic valve
      successfully diagnosed by transesophageal echocardiography.
AB  - Fibrous strand rupture is a rare cause of acute aortic regurgitation, but is a
      serious condition because of acute massive regurgitation. Therefore, prompt and
      accurate diagnosis is required. We saw a 53-year-old man who presented with acute
      dyspnea without evidence of infection. Transesophageal echocardiography revealed
      severe aortic regurgitation because of fibrous strand rupture. We performed
      surgery and found that the fibrous strand of the right coronary leaflet was
      ruptured. In cases of acute aortic regurgitation, the rupture of fibrous strand
      should be considered and transesophageal echocardiography would be very useful to
      diagnose it.

PMID- 29600572
TI  - Adenine alleviates iron overload by cAMP/PKA mediated hepatic hepcidin in mice.
AB  - Hemochromatosis is prevalent and often associated with high rates of morbidity
      and mortality worldwide. The safe alternative iron-reducing approaches are
      urgently needed in order to better control iron overload. Our unbiased vitamin
      screen for modulators of hepcidin, a master iron regulatory hormone, identifies
      adenine (vitamin B4) as a potent hepcidin agonist. Adenine significantly induced
      hepcidin mRNA level and promoter activity activation in human cell lines,
      possibly through BMP/SMAD pathway. Further studies in mice validated the effect
      of adenine on hepcidin upregulation. Consistently, adenine dietary supplement in
      mice led to an increase of hepatic hepcidin expression compared with normal diet
      fed mice via BMP/SMAD pathway. Notably, adenine-rich diet significantly
      ameliorated iron overload accompanied by the enhanced hepcidin expression in both
      high iron-fed mice and in Hfe-/- mice, a murine model of hereditary
      hemochromatosis. To further validate this finding, we selected pharmacological
      inhibitors against BMP (LDN193189). We found LDN193189 strongly blocked the
      hepcidin induction by adenine. Moreover, we uncovered an essential role of
      cAMP/PKA-dependent axis in triggering adenine-induced hepcidin expression in
      primary hepatocytes by using 8 br cAMP, a cAMP analog, and H89, a potent
      inhibitor for PKA signaling. These findings suggest a potential therapeutic role
      of adenine for hereditary hemochromatosis.

PMID- 29600573
TI  - The association between Helicobacter pylori infection and the risk of advanced
      colorectal neoplasia may differ according to age and cigarette smoking.
AB  - BACKGROUND: The association between Helicobacter pylori infection and advanced
      colorectal neoplasia (ACN) remains controversial. This study aimed to clarify the
      association between H. pylori infection and ACN according to age groups. METHODS:
      We retrospectively analyzed the association between H. pylori infection and ACN
      in patients aged <50 and >=50 years receiving a health checkup that included
      colonoscopy. Helicobacter pylori positivity was determined by the results of
      serum anti-H. pylori immunoglobulin G or rapid urease test, if the anti-H. pylori
      immunoglobulin G was in the borderline range. RESULTS: Among the 19 337 patients
      who were included, 56.2% and 3.4% were positive for H. pylori and ACN,
      respectively. Helicobacter pylori infection independently increased the risk of
      ACN in patients aged <50 years (odds ratio [OR], 1.602; 95% confidence intervals
      [CI], 1.194-2.150) but not in patients aged >=50 years (OR, 1.046; 95% CI, 0.863
      1.268). The positive association between H. pylori infection and ACN was affected
      by smoking history. When stratified by age and smoking history, H. pylori
      infection conferred an increased risk of ACN in patients aged <50 years with a
      history of smoking (OR, 1.926; 95% CI, 1.336-2.775) but not in the other 3 groups
      (3-way interaction test P = .023). Among patients aged <50 years with ACN, ACN in
      the left colon was found more frequently in patients with H. pylori infection and
      a history of smoking than in those without (69.3% vs 54.4%, respectively; P =
      .031). CONCLUSIONS: Helicobacter pylori infection confers an increased risk of
      ACN, but the association may differ according to age and smoking history.

PMID- 29600574
TI  - Quantitative assessment of mAb Fc glycosylation of CQA importance by capillary
      electrophoresis.
AB  - The attached carbohydrates at the highly conserved asparagine-linked
      glycosylation site in the CH 2 domain of the fragment crystallizable (Fc) region
      of monoclonal antibody therapeutics can play an essential role in their mechanism
      of action, including ADCC, CDC, anti-inflammatory functions, and serum half-life.
      Thus, this particular glycosylation represents one of the important critical
      quality attributes (CQA) of therapeutic monoclonal antibodies, which should be
      closely monitored and controlled during all stages of biopharmaceutical
      manufacturing. To study Fc glycosylation related quantitative critical quality
      attributes, the N-glycan pool of adalimumab (Humira(r) ) was spiked with
      increasing amounts of mannose-5 oligosaccharide, a glycan with high CQA
      importance. The method enabled precise quantitative CQA assessment with high
      detection sensitivity.

PMID- 29600575
TI  - Matrix metalloproteinase-9 expression of GCTSC in peripheral tissue and central
      tissue of GCTB.
AB  - Giant cell tumor stromal cell (GCTSC) is the tumor cell of giant cell tumor of
      bone (GCTB). The biomarkers characterization of GCTSC is critical for the
      selection of GCTB targeting drugs. We believe the main functions of GCTSC in
      different part of tumor should be different for different environment. Then the
      biological behavior and molecular biomarkers of GCTSC should be different as
      well. Based on this idea, we focused on GCTSC which located in central tissue,
      peripheral tissue and took MMP-9 as the breakthrough point to carry out research.
      The results showed MMP-9 staining grade of GCTSC which located in central tissue
      was slight, whereas multinucleated giant cell staining grade was high. The
      peripheral tissue was consisted by almost GCTSC with high MMP-9 staining degree
      and mRNA expression. This study also provided clues and inspiration for reducing
      GCTB recurrence rate after intralesional curettage with MMP-9 targeted therapy
      which were aimed at the residual peripheral tissue.

PMID- 29600576
TI  - Meta-analysis of trials comparing cefazolin to antistaphylococcal penicillins in
      the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia.
AB  - AIMS: The objective of this study was to determine the effectiveness and safety
      of cefazolin vs. antistaphylococcal penicillin (ASP) in the treatment of
      methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. METHODS: The
      databases of PubMed, Embase and Cochrane Central were used to identify
      comparative trials of cefazolin vs. ASP in MSSA bacteraemia. Meta-analysis of
      included trials was performed to assess any differences regarding mortality,
      clinical cure, recurrence and withdrawal from adverse effects between groups.
      Data were analysed using fixed effect model. Studies were weighted using Mantel
      Haenszel methodology. Heterogeneity was calculated using the I2 statistic.
      RESULTS: Nine retrospective and one prospective trials were identified involving
      4728 patients, 2954 with ASP and 1774 with cefazolin. Meta-analysis showed a
      lower mortality rate with cefazolin vs. ASP using fixed effect model [risk ratio
      (RR) 0.78, 95% confidence interval (CI) 0.69-0.88, P < 0.0001] with borderline
      high heterogeneity (I2  = 51%). Clinical cure was noted more often with cefazolin
      (RR 1.09, 95% CI 1.02-1.17, P = 0.02), although no difference was noted with
      relapse (RR 1.29, 95% CI 0.96-1.74 P = 0.09). Analysis also showed more
      withdrawals from adverse events with ASP vs. cefazolin (RR 0.27, 95% CI 0.16
      0.47, P < 0.00001). A minority of patients enrolled in these trials were admitted
      to the intensive care unit or had endocarditis (11.4% with ASP and 9% with
      cefazolin). CONCLUSION: Our meta-analysis of retrospective data demonstrate that
      cefazolin is more effective and safer ASP in patients with MSSA bacteraemia from
      various causes. Low quality of trials, borderline high heterogeneity, and
      possible publication bias may limit the validity of our findings. Randomized
      trials are needed to confirm these findings.

PMID- 29600577
TI  - Assessment of passive musculoarticular ankle stiffness in children, adolescents
      and young adults with haemophilic ankle arthropathy.
AB  - OBJECTIVES: To measure passive musculoarticular ankle stiffness (PMAAS) and its
      intra- and interday reliability in adult control subjects without ankle
      disorders. We also sought to quantify PMAAS in children, adolescents and young
      adults with haemophilia (CAAwH) taking into account the accurate tibiotalar and
      subtalar joints structural status obtained by magnetic resonance imaging (MRI).
      METHODS: We included 23 CAAwH and 23 typically developing boys (TDB) matched by
      age, weight and height, along with 25 healthy volunteers for reliability
      assessment. All CAAwH underwent bilateral ankle MRI, with anatomical status
      assessed using the International Prophylaxis Study Group MRI scale. All CAAwH
      underwent PMAAS testing for both sides randomly vs the dominant side (DS) in
      TDBs. For assessing viscous stiffness (VS) and elastic stiffness (ES), eight
      different oscillation frequencies were randomly repeated three times for each
      subject. RESULTS: Good-to-excellent intra- and interday reliability was observed
      for ES and VS variables. No relevant differences were observed between the ankle
      viscoelastic properties in CAAwH without joint damage and matched TDBs, whereas
      the study revealed significantly increased ES in the affected ankles of CAAwH
      with severe unilateral joint involvement compared to the non-affected joint.
      CONCLUSION: This study confirmed increased ES in the severely affected ankles of
      CAAwH compared to non-affected sides. No differences in the ankle viscoelastic
      properties of CAAwH with or without joint damage were observed, however, compared
      to matched TDB.

PMID- 29600578
TI  - Successful treatment of enteroatmospheric fistulas in combination with negative
      pressure wound therapy: Experience on 3 cases and literature review.
AB  - Enteroatmospheric fistulas (EAF) are rare but challenging and morbid
      complications of abdominal surgery and require time- as well as resource
      consuming management. Furthermore, they severely affect patients' quality of
      life. Several treatment modalities for EAF management are described in the
      literature. We describe 3 consecutive cases of EAF treatment by employing
      negative pressure wound therapy (NPWT) along with either a special silicone
      fistula adapter or a Silo-Vac-like system in another case to isolate the fistula
      from the remaining abdominal wound. Spontaneous fistula closure was achieved in 2
      of the 3 cases, and surgical resection of the small bowel segment harbouring EAF
      opening was possible in a third case after wound conditioning. The rate of
      fistula closure was 100% (n = 3/3). Compartmentalisation of the contaminated area
      using NPWT accelerated healing of the open abdominal wound remarkably. In
      summary, we present a useful tool for the challenging management of EAF and
      review the literature on different treatment options of EAF available today.

PMID- 29600579
TI  - Synthesis and Bioactivity of Polymer-Based Synthetic Mimics of Antimicrobial
      Peptides (SMAMPs) Made from Asymmetrically Disubstituted Itaconates.
AB  - A series of asymmetrically disubstituted diitaconate monomers is presented.
      Starting from itaconic anhydride, functional groups could be placed selectively
      at the two nonequivalent carbonyl groups. By using 2D NMR spectroscopy, it was
      shown that the first functionalization step occurred at the carbonyl group in the
      beta position to the double bond. These monomers were copolymerized with N,N
      dimethylacrylamide (DMAA) to yield polymer-based synthetic mimics of
      antimicrobial peptides (SMAMPs). They were obtained by free radical
      polymerization, a metal-free process, and still maintained facial amphiphilicity
      at the repeat unit level. This eliminates the need for laborious metal removal
      and is advantageous from a regulatory and product safety perspective. The
      poly(diitaconate-co-DMAA) copolymers obtained were statistical to alternating,
      and the monomer feed ratio roughly matched that of the repeat unit content of the
      copolymers. Investigations of varied R group hydrophobicity, repeat unit ratio,
      and molecular mass on antimicrobial activity against Escherichia coli and on
      compatibility with human keratinocytes showed that the polymers with the longest
      R groups and lowest DMAA content were the most antimicrobial and hemolytic. This
      is in agreement with the biological activity of previously reported SMAMPs. Thus,
      the design concept of facial amphiphilicity has successfully been transferred,
      but the selectivity of these polymers for bacteria over mammalian cells still
      needs to be optimized.

PMID- 29600581
TI  - An Alkylated Indacenodithieno[3,2-b]thiophene-Based Nonfullerene Acceptor with
      High Crystallinity Exhibiting Single Junction Solar Cell Efficiencies Greater
      than 13% with Low Voltage Losses.

PMID- 29600580
TI  - Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in
      moderate-to-severe psoriasis patients and control serum cholesterol levels.
AB  - OBJECTIVES: In this study, nanoparticles of curcumin were developed and orally
      administered to moderate-to-severe psoriasis (Psoriasis Area Severity Index
      values, PASI > 10) patients, in a placebo controlled, double blind, randomised
      clinical trial to evaluate the effectiveness. METHODS: Diverse binary systems of
      curcumin and hydrophilic polymers were investigated to optimise solubility and
      stability in terms of curcumin residual content and size of the crystals.
      Nanocrystals of curcumin stabilised with PVP (1 : 0.5, w/w), were characterised
      using X-ray diffraction, differential scanning calorimetry, TEM analyses and
      stability studies. The formulation was evaluated with a parallel artificial
      membrane permeability assay to predict the passive intestinal absorption. The
      first group of patients was treated orally with acitretin (0.4 mg/kg per day)
      plus nanocurcumin (3 g/day), the second group with acitretin, for 12 weeks. KEY
      FINDINGS: Curcumin nanoparticles were homogeneous and stable systems. Curcumin
      permeability was significantly enhanced when compared with aqueous saturated
      solution of curcumin. The reduction in PASI was significantly higher in patients
      treated with curcumin (P < 0.0001) and cholesterol serum levels remained
      unchanged in patients treated with acitretin plus nanocurcumin. CONCLUSIONS:
      Curcumin nanoparticles represent an effective adjuvant therapy in moderate-to
      severe psoriasis patients treated with oral acitretin, improving their lipid
      serum profile.

PMID- 29600582
TI  - Promoting interdisciplinary shared mental models.
AB  - BACKGROUND: Emergency Medicine (EM) and Hospital Medicine (HM) providers
      frequently interact when transitioning patients from the emergency department
      (ED) to the inpatient unit; however, there is infrequent collaboration between
      these subspecialties, and effective communication in EM-HM provider handover is
      an area for improvement. Shared mental models can enhance communication and
      safety. The purpose of this article is to describe the implementation of an
      interdisciplinary conference to allow providers to create shared mental models,
      and to assess the impact on attitudes and behaviours towards communication and
      collaboration outside the competing attentions of patient care environments.
      METHODS: The authors instituted a quarterly interactive case-based conference at
      an academic tertiary care children's hospital in which EM and HM subspecialty
      trainees co-facilitate evidence-based interactive presentations of clinical,
      diagnostic or management dilemmas. The conferences were evaluated via repeated
      cross-sectional surveys of EM and HM providers, as well as session evaluations.
      Surveys included multiple-choice, Likert-scale and free-text responses to assess
      the degree of interaction and collaboration between the divisions and provider
      attitudes toward changes in clinical practice. RESULTS: Assessment of the EM-HM
      collaborative conferences demonstrated trends towards increased interaction
      between divisions and increased discussion about management decisions among
      colleagues. Two-thirds of individuals who attended at least one conference felt
      that having attended an interdisciplinary conference influenced future management
      decisions. Effective communication in EM-HM provider handover is an area for
      improvement CONCLUSIONS: Interdisciplinary conferences provide a forum for cross
      specialty communication to discuss management differences in a low-stress
      educational environment, and allow providers to develop shared mental models for
      effective, safe patient care.

PMID- 29600583
TI  - Compositional Analysis of Coronary Artery Calcification in Dialysis Patients in
      vivo by Dual-Energy Computed Tomography Angiography.
AB  - While vascular calcification is an important factor regulating prognosis in
      dialysis patients, its components have not been adequately studied. We analyzed
      in vivo components of calcification in the coronary arteries of dialysis patients
      using the effective atomic number from dual-energy computed tomography. In
      dialysis patients (hemodialysis, N = 10; peritoneal dialysis, N = 12), average of
      median effective atomic number was 13.8 in the hemodialysis group, and 13.7 in
      the peritoneal dialysis group. No significant differences were seen between
      groups, with calcium oxalate monohydrate identified as the most common component
      in each. To confirm the accuracy of this method, we investigated the composition
      of surgically removed calcified tissues using already established methods.
      Comparison with the effective atomic number from dual-energy computed tomography
      showed that the results of calcification analysis were the same. We concluded
      that calcium oxalate monohydrate might be one of the major components of coronary
      artery calcification in dialysis patients.

PMID- 29600584
TI  - Plasma glutathione suggests oxidative stress is equally present in early- and
      late-onset bipolar disorder.
AB  - OBJECTIVES: We previously demonstrated oxidative stress in bipolar patients and a
      relationship between the age of illness onset and total glutathione, a principal
      antioxidant. In this study, we sought to replicate these findings in a new cohort
      of patients. METHODS: We recruited bipolar patients from Warneford Hospital,
      Oxford, UK, of similar age and grouped them according to age of onset of illness.
      The early-onset group comprised patients with onset at <23 years, and the late
      group comprised patients with onset at >30 years. A third group, comprising age
      matched healthy volunteers, was also included. Reduced and oxidized glutathione,
      cysteine, and cystine were determined in plasma, using high-performance liquid
      chromatography. Mitochondrial DNA copy number, measured in whole blood, was also
      compared between patients and healthy controls. RESULTS: Significant increases in
      oxidative stress were observed in the patient groups, compared with the control
      group; however, no differences in glutathione-related oxidative stress measures
      were detected between the early- and late-onset bipolar patient groups. No
      differences were observed in the amount of mitochondrial DNA, and there was no
      correlation with mood state. CONCLUSION: Using a more accurate method to quantify
      oxidative stress than in our previous study, we show that oxidative stress is a
      consistent feature of bipolar disorder. Although we did not reproduce our finding
      correlating age of onset of illness to oxidative stress, we have shown, once
      again, that oxidative stress is a consistent feature of bipolar disorder.

PMID- 29600585
TI  - Endoscopic treatment of post-supraglottoplasty stenosis.

PMID- 29600586
TI  - Early versus late readmission during the vulnerable phase following
      hospitalization for heart failure.

PMID- 29600587
TI  - TMEM16A inhibition impedes capacitation and acquisition of hyperactivated
      motility in guinea pig sperm.
AB  - Ca2+ -activated Cl- channels (CaCCs) are anionic channels that regulate many
      important physiological functions associated with chloride and calcium flux in
      some somatic cells. The molecular identity of CaCCs was revealed to be TMEM16A
      and TMEM16B (also known as Anoctamin or ANO1 and ANO2, respectively) in all
      eukaryotes. A recent study suggests the presence of TMEM16A in human sperm and a
      relationship with the rhZP-induced acrosome reaction. However, to the best of our
      knowledge, little is known about the role of TMEM16A in other spermatic processes
      such as capacitation or motility. In this study, we evaluated the effects of two
      TMEM16A antagonists on capacitation, acrosome reaction, and motility in guinea
      pig sperm; these antagonists were T16Ainh-A01, belonging to a second generation
      of potent antagonists of TMEM16A, and niflumic acid (NFA), a well-known
      antagonist of TMEM16A (CaCCs). First of all, we confirmed that the absence of Cl-
      in the capacitation medium changes motility parameters, capacitation, and the
      progesterone-induced acrosome reaction. Using a specific antibody, TMEM16A was
      found as a protein band of ~120 kDa, which localization was in the apical crest
      of the acrosome and the middle piece of the flagellum. Inhibition of TMEM16A by
      T16Ainh-A01 affected sperm physiology by reducing capacitation, blocking the
      progesterone-induced acrosome reaction under optimal capacitation conditions,
      inhibiting progressive motility, and the acquisition of hyperactivated motility,
      diminishing [Ca2+ ]i, and increasing [Cl- ]i. These changes in sperm kinematic
      parameters provide new evidence of the important role played by TMEM16A in the
      production of sperm capable of fertilizing oocytes.

PMID- 29600588
TI  - Cost-utility of a six-month programmed sports therapy (PST) in patients with
      haemophilia.
AB  - INTRODUCTION: Recurrent musculoskeletal haemorrhages in people with haemophilia
      (PwH) lead to restrictions in the locomotor system and, as a result, in physical
      performance, too. Due to its physical and psychological benefits, sport is
      increasingly re-commended for haemophilic patients. Evidence on the cost
      effectiveness of sports therapy is still lacking. AIM: The aim of this study was
      to determine the cost-effectiveness of a 6-month programmed sports therapy (PST).
      METHODS: The cost-effectiveness of the 6-month PST was assessed from a societal
      perspective alongside a RCT using cost-utility analysis. The analysis included 50
      PwH with moderate-to-severe haemophilia A and B and a training period over 6
      months. The health-related quality of life was measured with the EuroQoL-domain
      questionnaire. Resource utilization was assessed by questionnaire before and
      after the intervention. A cost-effectiveness acceptability curve was constructed,
      and sensitivity analyses were performed. RESULTS: During the 6-month study
      period, mean adjusted total healthcare costs were lower (mean difference: -22 805
      EUR; 95%-CI: -73 944-48 463; P = .59) and the number of QALYs was higher in the
      intervention group (mean difference: 0.3733; 95%-CI: 0.0014-0.0573; P = .04). The
      probability of an incremental cost-effectiveness ratio <50 000 EUR per QALY was
      71%. The performed sensitivity analysis confirmed these results. CONCLUSION:
      Results showed that the PST is effective in terms of a significant gain of QALYs.
      Furthermore, results weakly indicate the potential of the PST to reduce
      healthcare costs. Future studies should expand the observation period to have a
      closer look at the influence of PST on lifetime costs.

PMID- 29600589
TI  - Associations of Peritoneal Glucose Load With Male Sexual Dysfunction and
      Depression in Peritoneal Dialysis Patients.
AB  - This cross-sectional study examined possible associations of peritoneal glucose
      load with male sexual dysfunction and depression in peritoneal dialysis patients.
      Compared to patients with peritoneal glucose load <=3 g/kg per day, those with
      load >3 g/kg per day had higher Beck Depression Inventory scores, (18.9 +/- 5.4
      vs. 11.4 +/- 5.8, P = 0.002) and lower International Index of Erectile Function
      scores, serum total testosterone and DHEA [(15.4 +/- 6.4 vs. 45.1 +/- 20.7, P <
      0.001), (8.5 +/- 3.0 vs. 13.9 +/- 3.2, P < 0.001), (113.9 +/- 58.8 vs. 280.2 +/-
      128.3, P < 0.001); respectively)]. Of participants with peritoneal glucose load
      >3 g/kg per day, 84.6% had mild to moderate erectile dysfunction and 92.3% had
      abnormal Beck Depression Inventory scores. Peritoneal glucose load inversely
      correlated with International Index of Erectile Function scores (P < 0.001),
      total serum testosterone (P = 0.002) and serum DHEA (P = 0.001); and directly
      with Beck Depression Inventory scores (P < 0.001) and serum estradiol (P <
      0.001). This study demonstrated higher prevalence of sexual dysfunction,
      depression and sex hormone disturbances in male peritoneal dialysis patients
      receiving higher peritoneal glucose load.

PMID- 29600590
TI  - Molecular interactions of thymol with bovine serum albumin: Spectroscopic and
      molecular docking studies.
AB  - Thymol is the main monoterpene phenol present in the essential oils which is used
      in the food industry as flavoring and preservative agent. In this study, the
      interaction of thymol with the concentration range of 1 to 6 MUM and bovine serum
      albumin (BSA) at fixed concentration of 1 MUM was investigated by fluorescence,
      UV-vis, and molecular docking methods under physiological-like condition.
      Fluorescence experiments were performed at 5 different temperatures, and the
      results showed that the fluorescence quenching of BSA by thymol was because of a
      static quenching mechanism. The obtained binding parameters, K, were in the order
      of 104  M-1 , and the binding number, n, was approximately equal to unity
      indicating that there is 1 binding site for thymol on BSA. Calculated
      thermodynamic parameters for enthalpy (DeltaH), entropy (DeltaS), and Gibb's free
      energy (DeltaG) showed that the reaction was spontaneous and hydrophobic
      interactions were the main forces in the binding of thymol to BSA. The results of
      UV-vis spectroscopy and Arrhenius' theory showed the complex formation in the
      interaction of thymol and BSA. Negligible conformational changes in BSA by thymol
      were observed in fluorescence experiments, and the same results were also
      obtained from UV-vis studies. Results of molecular docking indicated that the
      subdomain IA of BSA was the binding site for thymol.

PMID- 29600591
TI  - Veteran-centred content in medical education.
AB  - BACKGROUND: Veterans have unique experiences that warrant special consideration
      in health care. Unfortunately, training in veteran-centred care has not been a
      clear focus of medical education, and only a very small proportion of medical
      schools include military cultural competency in their curricula. METHODS: We
      conducted an 80-minute focus group with six US veterans. Open-ended questions
      were used to elicit their perceptions of the health care that they receive, and
      how it can be improved. The audio-recording was transcribed verbatim and coded
      for thematic content. A phenomenological analytic approach was used to analyse
      the 31-page transcript and arrive at the final themes. RESULTS: Former service
      members from various periods of conflict (e.g. World War II, Vietnam, Persian
      Gulf) offered key insights about how to improve veterans' health care
      experiences. Veterans suggested that consideration of their previous military
      service would improve care. They lamented that the lack of military consciousness
      is a barrier to care. Finally, they suggested that clinicians pay close attention
      to the transition from service member to civilian, as reintegration to civilian
      life is a critical life experience. Training in veteran-centred care has not been
      a clear focus of medical education DISCUSSION: Veteran-centred care ensures
      optimal health care through ease of access to services, and through positive
      patient-provider interactions. Being aware of military culture can help providers
      to contextualise veterans' experiences and beliefs about health care seeking and
      illness management, particularly for invisible wounds of war, including traumatic
      brain injury (TBI) and post-traumatic stress disorder (PTSD).

PMID- 29600592
TI  - Successful multi-modal immune tolerance induction for factor IX deficiency with
      inhibitors and allergic reactions.

PMID- 29600593
TI  - Heteroannulation of Arynes with alpha-Amino Imides: Synthesis of 2,2
      Disubstituted Indolin-3-ones and Application to the Enantioselective Total
      Synthesis of (+)-Hinckdentine A.
AB  - A novel heteroannulation reaction between alpha-amino imides and in situ
      generated arynes has been developed for the synthesis of 2,2-disubstituted
      indolin-3-ones. An enantioselective total synthesis of the marine alkaloid (+)
      hinckdentine A was subsequently accomplished using this reaction as a key step. A
      catalytic enantioselective Michael addition of an alpha-aryl-alpha
      isocyanoacetate to phenyl vinyl selenone was employed for the construction of the
      enantioenriched alpha-quaternary alpha-amino ester.

PMID- 29600594
TI  - HBX protein promotes LASP-1 expression through activation of c-Jun in human
      hepatoma cells.
AB  - LIM and SH3 domain protein 1 (LASP-1) is known to participate in the progression
      of hepatocellular carcinoma (HCC). We previously showed that ectopic expression
      of hepatitis B virus (HBV) X protein (HBX) enhanced the expression of LASP-1,
      which promoted proliferation and migration of HCC cells. Here, we further
      demonstrated the molecular mechanism underlying upregulation of LASP-1, mediated
      by HBX, in HBV-infected HCC cells. Through a luciferase activity assay, we
      discovered that the LASP-1 promoter region regulated by HBX contained an AP-1
      binding element in human hepatoma cells. Interestingly, c-Jun, one subunit of AP
      1, was mainly responsible for activation, mediated by HBX, of the LASP-1
      promoter. Furthermore, HBX was shown not only to interact with phosphorylated c
      Jun in HCC cells but also to activate c-Jun by increasing the activation of PI3
      K/JNK signaling. Chromatin immunoprecipitation (ChIP) assay demonstrated that HBX
      was capable of binding to the LASP-1 promoter with c-Jun. Further, the expression
      levels of HBX were shown to be significantly positively correlated with that of
      LASP-1 and phosphorylatedc-Jun in HBV-related HCC tissues by immunohistochemistry
      analysis. In addition, the N-terminus of HBX was found to be responsible for the
      activation of c-Jun, as well as the expression of LASP-1. Taken together, these
      results suggest that HBX contributes to LASP-1 expression via the activation of c
      Jun to increase the promoter activity of LASP-1 in HBV-related HCC cells.

PMID- 29600595
TI  - The Tablets, Ring, Injections as Options (TRIO) study: what young African women
      chose and used for future HIV and pregnancy prevention.
AB  - INTRODUCTION: Preventing HIV and unintended pregnancies are key global health
      priorities. To inform product rollout and to understand attributes of future
      multipurpose prevention technologies (MPT) associated with preference and use, we
      evaluated three placebo delivery forms: daily oral tablets, a monthly vaginal
      ring, and two monthly intramuscular injections in TRIO, a five-month study among
      young Kenyan and South African women. METHODS: HIV-negative, sexually active, non
      pregnant women aged 18 to 30 were enrolled and randomized to use each placebo
      delivery form for one month (stage 1). Then, participants chose one product to
      use for two additional months (stage 2). We assessed safety, product ranking,
      choice, and use. We examined demographic and behavioural correlates of choice
      and, reciprocally, unwillingness to use in the future with logistic regression
      models. RESULTS: 277 women enrolled, 249 completed stage 1 and 246 completed
      stage 2. Median age was 23 years, 49% were Kenyan and 51% were South African.
      Three participants became pregnant during the study and one participant HIV
      seroconverted. There were 18 product-related adverse events, six tablets-related,
      11 ring-related, and one injection-related. After trying each product, 85%
      preferred a TRIO product over condoms. Injections were chosen most (64%, 95%
      confidence interval (CI) 58%, 70%; p < 0.001), and by more South Africans than
      Kenyans (odds ratio (OR) 2.01, 95% CI: 1.17, 3.43; p = 0.01). There was no
      significant difference in choosing tablets versus ring (21%, 95% CI: 16%, 26% vs.
      15%, 95% CI: 11%, 20%; p = 0.11). Tablet and ring adherence, based on direct
      observations and self-reports, improved over time. However, participants' self
      reported use of tablets did not match objective data from the electronic dose
      monitoring device. Participants were fully compliant with injections. CONCLUSION:
      In this population at risk for HIV and pregnancy, all participants agreed to
      choose and use a placebo MPT delivery form. A majority of participants preferred
      TRIO products to male condoms, an existing MPT. Injections were most liked and
      best used, however, they are years away from reaching the clinics. In the
      meantime, expanding the availability of tablets and giving access to rings can
      begin to fulfill the promise of choice for HIV prevention technologies and inform
      the development of suitable delivery forms as MPT.

PMID- 29600596
TI  - Quality by design-assisted development of a capillary electrophoresis method for
      the chiral purity determination of dexmedetomidine.
AB  - Dexmedetomidine is a selective alpha2 -adrenergic agonist used for patient
      sedation, while its enantiomer levomedetomidine has no sedative effects. As CE
      has been shown to be a powerful technique for enantiomer analysis, the aim of the
      study was the quality by design-based development of a CE-based limit test for
      the enantiomeric impurity levomedetomidine. The analytical target profile was
      defined that the method should be able to determine levomedetomidine with
      acceptable precision and accuracy at the 0.1% level. From initial scouting
      experiments, sulfated beta-cyclodextrin was selected as chiral selector. The
      critical process parameters were identified in a fractional factorial resolution
      V+ design, while a central composite face centered design and Monte Carlo
      simulations were used for defining the design space of the method. The selected
      working conditions were a 21.3/31.5 cm, 50 MUm id fused-silica capillary, a 50 mM
      sodium phosphate buffer, pH 6.5, containing 40 mg/mL sulfated beta-cyclodextrin,
      a capillary temperature of 17 degrees C and an applied voltage of 10 kV.
      Validation according to the ICH guideline Q2(R1) demonstrated repeatability and
      intermediate precision of content and migration time between 9.3 and 4.2% with
      accuracy in the range of 92.0 and 98.9%.

PMID- 29600597
TI  - MMP7 cleaves remyelination-impairing fibronectin aggregates and its expression is
      reduced in chronic multiple sclerosis lesions.
AB  - Upon demyelination, transient expression of fibronectin precedes successful
      remyelination. However, in chronic demyelination observed in multiple sclerosis
      (MS), aggregates of fibronectin persist and contribute to remyelination failure.
      Accordingly, removing fibronectin (aggregates) would constitute an effective
      strategy for promoting remyelination. Matrix metalloproteinases (MMPs) are
      enzymes known to remodel extracellular matrix components, including fibronectin.
      Here, we examined the ability of MMPs to degrade fibronectin aggregates. Our
      findings reveal that MMP7 cleaved fibronectin aggregates resulting into a
      prominent 13 kDa EIIIA (16 kDa EDA)-containing fragment. MMP7 was upregulated
      during lysolecithin-induced demyelination, indicating its potential for
      endogenous fibronectin clearance. In contrast, the expression of proMMP7 was
      substantially decreased in chronic active and inactive MS lesions compared with
      control white matter and remyelinated MS lesions. Microglia and macrophages were
      major cellular sources of proMMP7 and IL-4-activated, but not IFNgamma+LPS
      activated, microglia and macrophages secreted significant levels of proMMP7.
      Also, conditioned medium of IL-4-activated macrophages most efficiently cleaved
      fibronectin aggregates upon MMP-activating conditions. Yet, coatings of MMP7
      cleaved fibronectin aggregate fragments inhibited oligodendrocyte maturation,
      indicating that further degradation and/or clearance by phagocytosis is
      essential. These findings suggest that MMP7 cleaves fibronectin aggregates, while
      reduced (pro)MMP7 levels in MS lesions contribute to their persistent presence.
      Therefore, upregulating MMP7 levels may be key to remove remyelination-impairing
      fibronectin aggregates in MS lesions.

PMID- 29600598
TI  - Diagnosis of Meckel diverticulum on endoscopic retrograde ileography in a child.

PMID- 29600599
TI  - A Systematic Protocol for Benchmarking Guest-Host Interactions by First
      Principles Computations: Capturing CO2 in Clathrate Hydrates.
AB  - Clathrate hydrates of CO2 have been proposed as potential molecular materials in
      tackling important environmental problems related to greenhouse gases capture and
      storage. Despite the increasing interest in such hydrates and their technological
      applications, a molecular-level understanding of their formation and properties
      is still far from complete. Modeling interactions is a challenging and
      computationally demanding task, essential to reliably determine molecular
      properties. First-principles calculations for the CO2 guest in all sI, sII, and
      sH clathrate cages were performed, and the nature of the guest-host interactions,
      dominated by both hydrogen-bond and van der Waals forces, was systematically
      investigated. Different families of density functionals, as well as pairwise CO2
      @H2 O model potentials versus wavefunction-based quantum approaches were studied
      for CO2 clathrate-like systems. Benchmark energies for new distance-dependent
      datasets, consisting of potential energy curves sampling representative
      configurations of the systems at the repulsive, near-equilibrium, and
      asymptotic/long-range regions of the full-dimensional surface, were generated,
      and a general protocol was proposed to assess the accuracy of such conventional
      and modern approaches at minimum and non-minimum orientations. Our results show
      that dispersion interactions are important in the guest-host stabilization
      energies of such clathrate cages, and the encapsulation of the CO2 into guest
      free clathrate cages is always energetically favorable. In addition, the
      orientation of CO2 inside each cage was explored, and the ability of current
      promising approaches to accurately describe non-covalent CO2 @H2 O guest-host
      interactions in sI, sII, and sH clathrates was discussed, providing information
      for their applicability to future multiscale computer simulations.

PMID- 29600600
TI  - Early versus late readmission during the vulnerable phase following
      hospitalization for heart failure: reply.

PMID- 29600601
TI  - Pelvic Artery Calcification Score Is a Marker of Vascular Calcification in Male
      Hemodialysis Patients.
AB  - Patients who undergo hemodialysis often suffer from cardiovascular disease (CVD),
      and evaluation of coronary artery calcification is extremely important. These
      evaluations are typically conducted using a noninvasive method including electron
      beam computed tomography (CT) or multi-detector CT, and the Agatston method to
      calculate the coronary artery calcification score (CACS). However, it is
      difficult to use for patients undergoing dialysis. Because patients undergoing
      dialysis is too strong in coronary artery calcification, and results become
      incorrect. Therefore, we were looking for a calcified evaluation place peculiar
      to a patients undergoing dialysis. We obtained pelvic artery calcification scores
      (PACS) using a 64-row multi-slice CT to assess the presence of calcification
      within a triangular space bordered by bordered by osseous structure. We used the
      Agatston method to calculate PACS. We compared male patients undergoing dialysis
      with male patients with normal renal function. Patients undergoing hemodialysis
      had a significantly higher incidence of pelvic artery calcification than normal
      controls (79.7% vs. 5.5%). In the dialysis group, CACS was 1660.2 (0-9056.1), and
      PACS was 48.8 (0-2943.1). We found a correlation between PACS and CACS and
      between PACS and dialysis period. We found penile artery calcification in male
      patients undergoing hemodialysis was more than normal controls, and it was
      possible to quantify PACS using the Agatston method. This study suggested the
      possibility that PACS became the vascular calcification evaluation method of the
      hemodialysis patient.

PMID- 29600602
TI  - Performance evaluation of extended depth of field microscopy in the presence of
      spherical aberration and noise.
AB  - Effectiveness of extended depth of field microscopy (EDFM) implementation with
      wavefront encoding methods is reduced by depth-induced spherical aberration (SA)
      due to reliance of this approach on a defined point spread function (PSF).
      Evaluation of the engineered PSF's robustness to SA, when a specific phase mask
      design is used, is presented in terms of the final restored image quality.
      Synthetic intermediate images were generated using selected generalized cubic and
      cubic phase mask designs. Experimental intermediate images were acquired using
      the same phase mask designs projected from a liquid crystal spatial light
      modulator. Intermediate images were restored using the penalized space-invariant
      expectation maximization and the regularized linear least squares algorithms. In
      the presence of depth-induced SA, systems characterized by radially symmetric
      PSFs, coupled with model-based computational methods, achieve microscope imaging
      performance with fewer deviations in structural fidelity (e.g., artifacts) in
      simulation and experiment and 50% more accurate positioning of 1-MUm beads at 10
      MUm depth in simulation than those with radially asymmetric PSFs. Despite a drop
      in the signal-to-noise ratio after processing, EDFM is shown to achieve the
      conventional resolution limit when a model-based reconstruction algorithm with
      appropriate regularization is used. These trends are also found in images of
      fixed fluorescently labeled brine shrimp, not adjacent to the coverslip, and
      fluorescently labeled mitochondria in live cells.

PMID- 29600603
TI  - [Current research situation of nephrotoxicity of Chinese herbal medicine].
AB  - To provide the basis for the future research on the nephrotoxicity of Chinese
      herbal medicine through systematic and comprehensive summary of all the Chinese
      herbal medicines which may lead to nephrotoxicity. Foreign resources included
      PubMed and Cochrane library, and domestic research resources was China Food and
      Drug Administration(CDFA) Adverse Drug Reaction Monitoring Center database. The
      databases were searched from establishment to January 1, 2017. There was no
      limitation on research type. 28 English studies were found, including 97 Chinese
      herbs or prescriptions with the risk of nephrotoxicity. The following six Chinese
      herbal medicines with the risk of nephrotoxicity had a large number of studies:
      aristolochic acid(5 studies), Tripterygium wilfordii(4 studies), Erycibe
      obtusifolia(2 studies), Rheum palmatum(2 studies), Ephedra sinica(2 studies), and
      Atractylodes lances(2 studies). The remaining 91 Chinese medicines were reported
      with risk of nephrotoxicity in only 1 study respectively. CDFA reported 16
      Chinese herbal medicines with the risk of nephrotoxicity, including Ganmaoqing
      Pian(capsule), Zhenju Jiangya Pian, T. wilfordii preparation, Vc-Yinqiao Pian,
      Chuanhuning injection, Shuanghuanglian injection, Qingkailing injection,
      Lianbizhi injection, herbal decoction containing Aristolochiae Radix, Guanxin
      Suhe Wan, Shugan Liqi Wan, Ershiwuwei Songshi Wan, herbal decoction containing
      Aristolochia Fangchi, herbal granules containing root of Kaempfer Dutchmanspipe,
      Ganmaotong(tablets), and Longdan Xiegan Wan. Currently, in addition to
      aristolochic acids, the most reported Chinese herbal medicine with the risk of
      nephrotoxicity is T. wilfordii preparation.

PMID- 29600604
TI  - [Evidence-based evaluation on safety of Tripterygium wilfordii preparations].
AB  - The study was aimed to conduct an evidence-based evaluation on the safety of
      Tripterygium wilfordii(TW) preparations through a method combined bibliometrics
      research with evidence-based evaluation research, to provide evidence-based
      safety information of the TW preparations(nephrotoxicity) for the government
      decision-making and clinical application, and to provides methods and suggestions
      for evaluating nephrotoxicity of Chinese herbal medicine(CHM) in the future. We
      searched relevant databases at home and abroad systematically, and six Chinese
      and English databases including CNKI, SinoMed, VIP, WanFang, PubMed, and Cochrane
      library were comprehensively searched. All types of research documents about the
      safety of TW preparations. Literature were screened and extracted based on
      inclusion and exclusion criteria. The methodology quality of all included studies
      were assessed by internationally recognized evaluation tools or standards. The
      incidence rate was analyzed by using R software. Subgroup analysis were conducted
      according to the type of disease treated, drug delivery way, medication time, and
      study types.

PMID- 29600605
TI  - [Evaluation of reporting quality of RCT on nephrotoxicity of Tripterygium
      wilfordii preparations according to CONSORT HARMs statement].
AB  - To evaluate the quality of randomized controlled trials(RCT) on nephrotoxicity of
      Tripterygium wilfordii preparations according to the CONSORT HARMs statement. The
      report quality of each included study was evaluated according to the CONSORT
      HARMs statement, and the number of entries that comply with CONSORT HARMs
      statement was calculated in each study to evaluate the report quality on
      nephrotoxicity-related adverse reactions of T. wilfordii preparations and
      summarize the problems in domestic studies on nephrotoxicity-related adverse
      reactions. A total of 16 RCTs were included, with an average of 7 entries
      complying with CONSORT HARMs statement per study. The report of the nephrotoxic
      associated RCT of T. wilfordii preparations was of poor quality and the most non
      repeating entries included the following ones: using validated tools to report
      adverse effects, standards for coding of the adverse reactions, describing how
      and when to collect data on adverse reactions in Method, describing how adverse
      reactions are attributed to T. wilfordii, clearly stating who has reported the
      adverse reactions, describing the analysis method of adverse reactions,
      describing the method of collecting recurrent adverse reaction data, describing
      any subgroup analysis and exploratory analysis associated with the hazard. We
      suggest that the studies on adverse reactions of traditional Chinese medicine
      should strictly report the entries according to the CONSORT HARMs statement, and
      take the characteristics of traditional Chinese medicine into account to report
      the details of the Chinese medicine like compositions, dose, taking time,
      combined medication and the dialectical typology of research objects.

PMID- 29600606
TI  - [Application of evidence-based rapid review in studying nephrotoxicity of
      Tripterygium wilfordii preparation].
AB  - To investigate the feasibility of applying the evidence-based rapid review in
      studying the nephrotoxicity of Tripterygium wilfordii preparation. We used four
      methods in relevant studies on the nephrotoxicity of T. wilfordii preparation.
      The first method had no limitation on any search terms, which was a traditional
      approach to retrieve systematic reviews. The second method limited the relevant
      search terms of T. wilfordii preparation to "all of CHMs containing T. wilfordii
      preparation approved by CFDA". The third method was to limit the relevant
      retrieval terms of nephrotoxicity as the "most frequently reported terms related
      to nephrotoxicity found in the study literature screening process in the early
      stage of systematic review". The fourth method was to limit the search terms
      relating to both T. wilfordii preparation and nephrotoxicity. Finally, the
      results of the last three search methods were compared with those of the first
      search method, and the feasibility of the rapid review method in the study for
      the nephrotoxicity of CHM was discussed. For the total number of literatures
      searched, the fourth method had the smallest number of literatures. For the
      number of articles in line with the inclusion criteria, the second method had the
      largest number of eligible literatures. For the type of literatures included, the
      forth method had a higher coincidence degree. The forth method was the best one,
      because it was not only consistent with the results, but also could minimize the
      workload. Rapid review is feasible in the study of nephrotoxicity of T.
      wilfordii.

PMID- 29600607
TI  - [Development of bioassay method in quality control of traditional Chinese
      medicine].
AB  - On the basis of chemical content determination, the bioassay methods can be used
      to comprehensively evaluate and control the Chinese medicine compound. This paper
      analyzed the newly published literature on traditional Chinese medicine(TCM)
      bioassay. The selection of standard control substances and the establishment of
      experimental system are the main difficulties in bioassay. At present, the
      standard control substances mainly include: different sources of products with
      basically similar components, certified medicinal materials, genuine medicinal
      materials, commonly used chemical drugs or biological products with similar
      pharmacological functions, as well as Chinese medicine potency conversed by
      activity of biological products. In this paper, the common bioassays would be
      summarized from the clinical efficacy of activating blood circulation and
      removing stasis and clearing heat and detoxification. It is one of the important
      contents in the industrial production of traditional Chinese medicine to
      gradually establish the bioassay platform of Chinese medicine from the
      enterprise's internal control to the industry. recognition.

PMID- 29600608
TI  - [CircRNA as a new field in human disease research].
AB  - For the characteristics of high stability, high conservation between species, and
      tissue specificity, circular RNA(circRNA) has been expected to become a new
      molecular biomarker for the clinical diagnosis, treatment and prognosis, and the
      potential target for targeted therapy. Study on the traditional Chinese
      medicine(TCM) syndrome includes not only the macro indexes collected by using
      four traditional methods of diagnosis, but also contains some micro information
      that can not be achieved by using the four traditional diagnosis methods. The
      questions such as how to deal with the relationship between the holistic concept
      of TCM and micro research, and how to solve the contradiction between the
      fuzziness of syndrome description and the accuracy of microscopic research, need
      to be considered before the micro research in TCM syndrome. circRNA as a new
      field of understanding human disease, may provide some ideas for the TCM syndrome
      research due to its characteristics. Overall, it is necessary to pay attention to
      explore the molecular level with same syndrome in different diseases and reveal
      the connotation and essence of syndromes by understanding of circRNA.

PMID- 29600609
TI  - [Comparison and review on specifications of fermented Cordyceps sinensis
      products].
AB  - There are five kinds of fermented Cordyceps crude drug and their preparations
      that have been approved as medicine on the market. Since the initial strains of
      the crude drug were all isolated from natural Cordyceps sinensis, they have
      similar names, chemical components and even clinical applications. However,
      because of the different strain species and fermentation processes, there was
      significant difference in quality. As a result, they should be clearly
      distinguished in clinical use. Most of the products were researched and developed
      during the 1980s and 1990s, so there was difference in quality standards for
      different products, and their quality control levels of some products were not
      perfect. At present, some of the products are approved as Chinese medicine,
      others are approved as chemical drugs, with a confusion in products name,
      management and clinical application. In this paper, the approval numbers, quality
      standards and clinical applications, and current problems of these products were
      summarized and compared; some suggestions were put forward, such as standardizing
      the product name, unifying the management of approval number category, and
      increasing the specific quality control attributes, in order to provide reference
      for standard implementation, quality control and drug regulation for fermented
      Cordyceps crude drugs and their preparations.

PMID- 29600610
TI  - [Influence of light on gene expression of key synthesis enzyme genes FtANR and
      FtLAR about proanthocyanidin in seeds of homologous plant of food and medicine
      Fagopyrum tataricum].
AB  - Tartary buckwheat Fagopyrum tataricum is an important medicinal and functional
      herb due to its rich content of flavonoids in the seeds. F.tataricum exhibited
      good functions for free radicals scavenging, anti-oxidation, anti-aging
      activities. Although much genetic knowledge of the synthesis, regulation,
      accumulation of rutin, the genetic basis of proanthocyanidins(PAs) in tartary
      buckwheat and their related gene expression changes under different lights(blue,
      red, far red, ultraviolet light) remain largely unexplored. In this study, we
      cloned one anthocyanidin reductase gene(ANR) and two leucocyanidin reductase
      gene(LAR) named FtANR,FtLAR1,FtLAR3 involved in formation of(+)-catechin and(-)
      epicatechin precusor proanthocyanidin by digging out F. tataricum seed
      transcriptome data. The expression data showed that the opposite influence of red
      light on these gene transcript level compared to others lights. The expression
      levels of FtANR and FtLAR1 decreased and FtLAR3 appeared increment after exposed
      in the red light, while the expression levels of those genes appeared opposite
      result after exposed in the blue and far red light.

PMID- 29600611
TI  - [Identification of endophytic bacteria BZJN1 and research on biological control
      of root rot of Atractylodes macrocephala].
AB  - In this study, an endophytic bacteria strain BZJN1 was isolated from Atractylodes
      macrocephala, and identified as Bacillus subtilis by physiological and
      biochemical tests and molecular identification. Strain BZJN1 could inhibit the
      growth of mycelia of Ceratobasidium sp. significantly, and the inhibition rate
      was more than 70%. The mycelium growth deformity with bulge as spherical and
      partially exhaustible in apex or central with microscopic observation. The
      inhibitory rates under 3% and 6% concentrations of the cell free fermentation
      were 22.7% and 38.7% expectively. The field test proved that the control efficacy
      of treatment of 1*108 cfu.mL-1 is 75.27% and 72.37% after 10 and 20 days. All the
      treatments of strain BZJN1 was able to promote the growth of A. macrocephala, the
      treatment of 1*108 cfu.mL-1 could able to increase the yield to 14.1%.

PMID- 29600612
TI  - [Construction of yeast two-hybrid library of Salvia miltiorrhiza and screening of
      SmJAZ8 interaction protein].
AB  - The study is aimed to construct high quality Salvia miltiorrhiza cDNA library and
      obtain the SmJAZ8 gene of S. miltiorrhiza by yeast two-hybrid system. In this
      study, full-length cDNA was synthesized from roots, stems, leaves, flowers and
      hairy roots of S. miltiorrhiza. The full-length cDNA library was synthesized by
      SMART method and constructed with DSN homogenization technique. The results
      showed that the library capacity was 1.45*106, the recombination rate was 100%,
      and the average size of the insert was 500-2 000 bp. The recombinant vector of
      pDEST-pGADT7-SmJAZ8 was constructed and transformed into Y2HGold strain. The
      interaction protein was screened by yeast two-hybrid system. The DnaJ protein and
      UBQ protein were screened by yeast two-hybrid system. This study has successfully
      constructed a full-length cDNA library of S. miltiorrhiza, and laid the
      foundation for the follow-up study on functional gene screening and gene function
      of S. miltiorrhiza.

PMID- 29600613
TI  - [Identification and analysis of NAC family in ginger(Zingiber officinale) based
      on RNA-seq data].
AB  - The NAC family is an important transcription factor which regulate plant growth
      and development, signal transduction, and stress response.In this study, the
      protein identification, subfamily classification, the determination of physical
      and chemical properties, protein structure, and expression pattern of NAC family
      were performed using bioinformatic methods based on the RNA-seq data of ginger.
      The results showed that a total of 72 NAC transcription factors were identified
      in 271.1 Mb total nucleotides, and they could be clustered into 13 subfamilies
      according to the phylogenetic tree.The physical and chemical properties,
      structure analysis revealed that the amino acid number and isoelectric point were
      different among 13 NAC subfamilies; the secondary structure of NACs transcription
      factors mainly consist of random coil, and the tertiary structure is similar.In
      addition,the expression patterns of genes under different soil moisture and
      Ralstonia solanacearum infection showed that 23 NACs were differentially
      expressed, which were mainly distributed in VIII,VII, and XV subfamilies related
      to plant senescence, hormone metabolism and cell wall metabolism.The results
      provide some valuable information for the research and development of NAC
      transcription factors in ginger.

PMID- 29600614
TI  - [Comparison of saponins from Gynostemma pentaphyllum leaves prepared by different
      processing methods].
AB  - To investigate the differences of chemical compositions in Gynostemma
      pentaphyllum leaves prepared by different processing methods. Ultra performance
      liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)
      was used to compare the chemical compositions between shade-dried processing and
      drum-dried processing. Forty six gypenosides were identified by control
      comparison, liquid chromatography-mass spectrometry(LC-MSn) fragmentation
      information, and literature data. The mass spectral peak area statistics was
      combined with principal component analysis(PCA), and the results showed that
      eight batches of Gynostemma pentaphyllum leaves samples were divided into two
      groups according to the two different processing methods; ten chemical
      compositions with significant differences were screened according to mass
      spectrum information combined with partial least-squares discriminant
      analysis(PLS-DA). The result showed that most parent nucleus of the gypenosides
      contained three to four glycosides in drum-dried samples, and one to two
      glycosides in the shade-dried samples. It was inferred from further MS analysis
      that desugarization of gypenosides was present to produce secondary glycosides
      with the effect of glucosidase in the shade-drying, thus resulting in difference
      in compositions. This study provided data support for harvesting, processing and
      quality control of Gynostemma pentaphyllum leaves.

PMID- 29600615
TI  - [Biopharmaceuticals classification system(BCS) of nuciferin in Nelumbinis
      Folium].
AB  - Nuciferin is the main active ingredients in Nelumbinis Folium, which was proved
      to have good hypolipidemic, antioxidative and anti-inflammatory bioactivities.
      Currently, in vivo pharmacokinetic studies of nuciferin showed different results
      based on different animal models. In vitro evaluation experiments were low-cost,
      stable and controllable. Biopharmaceutical classification system(BCS) was an
      effective and reliable in vitro simulation method to evaluate the bioavailability
      of oral drugs. It was a scientific framework for classifying drugs or active
      pharmaceutical ingredients(API) according to their solubility and impermeability
      in vitro. In the study, BCS was applied in an active ingredient in traditional
      Chinese medicine(TCM), which was consisted of numerous chemical components. To
      study the equilibrium solubility of nuciferine, ideal solution model, Ape blat
      model and polynomial model were adopted. The permeability was measured based on
      partition coefficient(logP) and distribution coefficient(logD). Besides, in vitro
      apparent permeabilities of Caco-2 cells and murine intestine tissues were
      evaluated. Nuciferine was classified as BCSI, since it had a good solubility and
      permeability in all methods under acidic conditions. However, in neutral and
      alkaline environments, nuciferine was classified as BCSIV by using everted
      intestinal sac. It indicated that the species of experimental animals has a
      significant influence on the absorption of nuciferine. This experiment can
      provide data support to the prediction in a complex environment(medicinal
      materials and absorbed parts). The application of BCS on TCM ingredients provided
      a new in vitro method to evaluate and screen out the druggability of TCM
      ingredients.

PMID- 29600616
TI  - [Freeze drying process optimization of ginger juice-adjuvant for Chinese materia
      medica processing and stability of freeze-dried ginger juice powder].
AB  - Ginger juice, a commonly used adjuvant for Chinese materia medica, is applied in
      processing of multiple Chinese herbal decoction pieces. Because of the raw
      materials and preparation process of ginger juice, it is difficult to be
      preserved for a long time, and the dosage of ginger juice in the processing can
      not be determined base on its content of main compositions. Ginger juice from
      different sources is hard to achieve consistent effect during the processing of
      traditional Chinese herbal decoction pieces. Based on the previous studies, the
      freeze drying of ginger juice under different shelf temperatures and vacuum
      degrees were studied, and the optimized freeze drying condition of ginger juice
      was determined. The content determination method for 6-gingerol, 8-gingerol, 10
      gingerol and 6-shagaol in ginger juice and redissolved ginger juice was
      established. The content changes of 6-gingerol, 8-gingerol, 10-gingerol, 6
      gingerol, 6-shagaol, volatile oil and total phenol were studied through the
      drying process and 30 days preservation period. The results showed that the
      freeze drying time of ginger juice was shortened after process optimization; the
      compositions basically remained unchanged after freeze drying, and there was no
      significant changes in the total phenol content and gingerol content, but the
      volatile oil content was significantly decreased(P<0.05). Within 30 days, the
      contents of gingerol, total phenol, and volatile oil were on the decline as a
      whole. This study has preliminarily proved the feasibility of freeze-drying
      process of ginger juice as an adjuvant for Chinese medicine processing.

PMID- 29600617
TI  - [Identification of metabolites of Chenxiang Huaqi pill in rats based on UPLC-Q
      TOF-MS].
AB  - To analyze the metabolites of Chenxiang Huaqi pill in rats by using ultra
      performance liquid chromatography-quadrupole-time of flight-mass spectrometry
      (UPLC-Q-TOF-MS). The separation was performed on Phenomenex Kinetex C18 column,
      with the acetonitrile -0.1% formic acid as the mobile phase for gradient elution
      at a flow rate of 0.8 mL.min-1. The data were collected by the positive ion mode
      of ESI source. The plasma and urine total ion chromatograms of the rats in blank
      group and treatment group were used to analyze the targeted ion chromatograms.
      The results showed that 24 compounds were detected in the plasma and urine,
      including 5 prototype components and 19 metabolites. The major metabolic pathways
      included hydration, glucuronidation, demethylation, hydrolysis, hydroxylation and
      sulfation. The method was rapid, simple and sensitive, and can be used to rapidly
      identify the metabolites of Chenxiang Huaqi pill that can be absorbed in rats,
      providing a reference for the study of the absorption and metabolism mechanism of
      Chenxiang Huaqi pill in vitro.

PMID- 29600618
TI  - [A new dimeric xanthanolide from fruits of Xanthium chinense].
AB  - Through the methods of polyamide resin, Sephadex LH-20, ODS column chromatography
      and preparative HPLC etc., 7 compounds were isolated from the 70% ethanol extract
      of the fruits of Xanthium chinense. Based on ESI-MS and NMR data, the structures
      of these compounds were identified as pungiolide O(1), grasshopper ketone(2),
      icariside F2(3), 7-[(beta-D-apiofuranosyl-(1->6)-beta-D-glucopyranosyl)oxymethy]
      8,8-dimethyl-4,8-dihydrobenzo[1,4]thiazine-3,5-dione(4),(6R,9S)-3-oxo-alpha-ionol
      beta-D-glucopyranoside(5), cryptochlorogenic acid methyl ester(6), and
      chlorogenic acid methyl ester(7). Among them, compound 1 is a new compound.

PMID- 29600619
TI  - [Limonoids from seeds of Azadirachta indica and their cytotoxic activity].
AB  - Eight limonoids were isolated from 95% ethanol extracts of neem(Azadirachta
      indica) seeds by various chromatographic methods. By comparison of their
      spectroscopic data with those reported in the literatures, these limonoids were
      determined as salannin(1), 1-detigloyl-1-isobutylsalannin(2), salannol-3
      acetate(3), salannol(4), spirosendan(5), 1-detigloyloxy-3-deacetylsalannin-1-en-3
      one(6), nimbin(7) and 6-deacetylnimbin(8). Compounds 2 and 5 were firstly
      isolated from this genus and 5 represented the only example of its type. And 6 is
      a new natural product. 6 showed inhibitory activity against HeLa and HL-60 cells,
      with IC50 of(21.61+/-4.37) and(27.33+/-5.74) MUmol.L-1, respectively. Both 7 and
      8 mildly inhibited the growth of HeLa cells, with IC50 of (33.15+/-5.24) and
      (38.56+/-6.41) MUmol.L-1, respectively.

PMID- 29600620
TI  - [Study on difference of flavonoids content in stems and leaves of Mentha
      Haplocalycis Herba in different harvest periods].
AB  - The dynamic changes of active components in stems and leaves of Mentha
      Haplocalycis Herba(mint) at different harvest periods were investigated, and the
      optimum harvest time of mint was explored. In this study, hesperidin, diosmin,
      didymin and buddleoside were selected as flavonoids index components of mint, and
      the QAMS method was established to measure the contents of these flavonoids in
      mint. The contents of 4 flavonoid glycosides in the mint stems and leaves from
      three habitats harvested in different time were studied and evaluated
      comprehensively using statistical analysis and principal component analysis
      (PCA). The results showed that the contents of 4 components in the leaves are
      higher than that in the stems despite of habitats and harvest time, and they all
      exhibited dynamic changes along with the harvest periods within the same habitat.
      Three harvest periods in mid April, mid September and late October scored higher
      in comprehensive evaluation in Jiangsu region, the genuine producing area of
      Mentha Haplocalycis Herba. Combined with the yield and contents of active
      compounds, the optimum harvest time of mint in Jiangsu region was mid September
      and late October, which is basically consistent with the traditional harvesting
      periods.

PMID- 29600621
TI  - [Feasibility study of QAMS for quantitative analysis of multiple structural types
      of ingredients in Atractylodis Rhizome by GC].
AB  - In this study, quantitative analysis of multi-components with single marker(QAMS)
      was established and validated to simultaneously determine four
      sesquiterpenoids(beta-eudesmol, atractylon, atractylolideI, atractylolide II) in
      Atractylodis Rhizome based on the gas chromatographic method(GC). Using beta
      eudesmol as the contrast, the relative correctionfactors(RCF) of the other three
      sesquiterpenoids were determined by GC. Within the line arranges,the values of
      RCF of beta-eudesmol to atractylon, atractylolideIand atractylolide II were
      0.823, 0.690 and 0.766, respectively. The RCF had a good reproducibility in
      various instruments, chromatographic columns. According to their RCF, we
      simultaneously determined four sesquiterpenoids in Atractylodis Rhizome only
      using one marker. The results of QAMS method were validated by comparing with
      that of internal standard method, and no obvious significant difference was
      found.

PMID- 29600622
TI  - [Analysis of chondroitin sulfate content of Cervi Cornu Pantotrichum with
      different processing methods and different parts].
AB  - The differences and the variations of chondroitin sulfate content in different
      parts of Cervi Cornu Pantotrichum(CCP) with different processing methods were
      investigated. The chondroitin sulfate from velvet was extracted by dilute alkali
      concentrated salt method. Next, the chondroitin sulfate was digested by
      chondroitinase ABC.The contents of total chondroitin sulfate and chondroitin
      sulfate A, B and C in the samples were determined by high performance liquid
      chromatography(HPLC).The content of chondroitin sulfate in wax,powder,gauze,bone
      slices of CCP with freeze-drying processing is 14.13,11.99,1.74,0.32 g.kg-1,
      respectively. The content of chondroitin sulfate in wax,powder,gauze,bone slices
      of CCP with boiling processing is 10.71,8.97,2.21,1.40 g.kg-1, respectively. The
      content of chondroitin sulfate in wax,powder,gauze,bone slices of CCP without
      blood is 12.47,9.47,2.64,0.07 g.kg-1, respectively. And the content of
      chondroitin sulfate in wax,powder,gauze,bone slices of CCP with blood is
      8.22,4.39,0.87,0.28 g.kg-1 respectively. The results indicated that the
      chondroitin sulfate content in different processing methods was significantly
      different.The content of chondroitin sulfate in CCP with freeze-drying is higher
      than that in CCP with boiling processing.The content of chondroitin sulfate in
      CCP without blood is higher than that in CCP with blood. The chondroitin sulfate
      content in differerent paris of the velvet with the same processing methods was
      arranged from high to low as: wax slices, powder, gauze slices, bone slices.

PMID- 29600623
TI  - [Effect and mechanism of Mahuang Tang against influenza A/H1N1 virus in vitro].
AB  - To study the effect and underlying mechanism of Mahuang Tang against influenza A
      virus in vitro, the influenza virus-infected Madin-Darby canine kidney(MDCK)
      cells were used as the carrier in this study to detect the median tissue culture
      infective dose(TCID50) of influenza A virus strains(A/PR8/34) on MDCK cells with
      cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and
      anti-influenza virus biosynthesis were used as two different administration
      methods, and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to
      determine the antiviral effective rate(ER), median efficacious
      concentration(EC50) and therapeutic index(TI) of Mahuang Tang. The quantitative
      Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and
      the mRNA expression levels of TLR4, TLR7, MyD88 and TRAF6 in MDCK cells at 24, 48
      h after the treatment. The experiment results indicated that TCID50 of A/PR8/34
      for MDCK cells was 1*10-4.32/mL. The EC50 values of two different treatment
      methods were 4.92,1.59 g.L-1 respectively, the TI values were 12.53, 38.78
      respectively, and when the concentration of Mahuang Tang was 5.00 g.L-1, ER
      values were 50.21%, 98.41% respectively, showing that Mahuang Tang can block
      influenza virus into the host cells and significantly inhibit their biosynthesis.
      Meanwhile, as compared with the virus group, the virus load was significantly
      inhibited in Mahuang Tang groups, and Mahuang Tang high and middle doses had the
      significant effect on decreasing the mRNA expression of TLR4, TLR7,MyD88 and
      TRAF6 at 24, 48 h after the treatment. It can be demonstrated that the mechanisms
      of Mahuang Tang against influenza A virus are related to the inhibition of
      influenza virus replication and the mRNA expression of correlative genes in TLR4
      and TLR7 signaling pathways.

PMID- 29600624
TI  - [Protective effects of genistein on Abeta25-35-induced PC12 cell injury via
      regulating CaM-CaMKIV signaling pathway].
AB  - Genistein is a kind of isoflavone compounds, also called phytoestrogens, with
      clinical effects on cardiovascular disease, cancer and postmenopausal-related
      gynecological diseases, and also has the potentiality in the prevention and
      treatment of Alzheimer's disease(AD). In this study, the protective effect of
      genistein on Abeta25-35-induced PC12 cell injury and effect on CaM-CaMKIV
      signaling pathway were observed to investigate its mechanism for AD. PC12 cells
      were cultured in vitro and then the safe concentration of genistein and the
      modeling concentration and optimal time point of administration of Abeta25-35
      were screened by MTT assay. After being pretreated with different concentrations
      of genistein(25, 50, 100 MUmol.L-1) on PC12 cells, the AD model of PC12 cells was
      induced by Abeta25-35. Then the survival rate of cells was detected by MTT assay;
      morphological change of cells was observed under the inverted microscope, and
      apoptosis of cells was assessed by AO/EB fluorescence staining; the
      neuroprotective effects of genistein on AD cell model were observed and the
      optimal concentration of genistein was determined. Expressions of mRNA and
      protein levels of CaM, CaMKK, CaMKIV and tau were detected by qRT-PCR and Western
      blot assay, respectively. The results showed that as compared with the blank
      group, the cell survival rate was decreased; the cell damage and apoptosis were
      increased; and the expressions of mRNA and protein levels of CaM, CaMKK, CaMKIV
      and tau were increased in AD model group. Genistein could significantly improve
      the cell survival rate, reduce the cell damage and apoptosis of AD cell model,
      and significantly down-regulate the expressions of mRNA and protein levels of
      CaM, CaMKK, CaMKIV and tau of AD cell model. These results indicated that
      genistein has obviously neuroprotective effect on the AD cell model induced by
      Abeta25-35, and the mechanism may be related to the down-regulation of CaM-CaMKIV
      signaling pathway and Tau protein expression.

PMID- 29600625
TI  - [Effect of microRNA-34a/SIRT1/p53 signal pathway on notoginsenoside R1 delaying
      vascular endothelial cell senescence].
AB  - This study aimed to investigate the effect of notoginsenoside R1 in delaying H2O2
      induced vascular endothelial cell senescence through microRNA-34a/SIRT1/p53
      signal pathway. In this study, human umbilical vein endothelial cells(HUVECs)
      were selected as the study object; the aging model induced by hydrogen
      peroxide(H2O2) was established, with resveratrol as the positive drug. HUVECs
      were randomly divided into four groups, youth group, senescence model group,
      notoginsenoside R1 group and resveratrol group. Notoginsenoside R1 group and
      resveratrol group were modeled with 100 MUmoL.L-1 H2O2 for 4 h after 24 h
      treatment with notoginsenoside R1(30 MUmoL.L-1) and resveratrol(10 MUmoL.L-1)
      respectively. At the end, each group was cultured with complete medium for 24 h.
      The degree of cellular senescence was detected by senescence-associated beta
      galactosidase(SA-beta-Gal) staining kit, the cell viability was detected by cell
      counting kit-8, the cell cycle distribution was analyzed by flow cytometry, and
      the cellular SOD activity was detected by WST-1 method in each group. The
      expressions of SIRT1, p53, p21 and p16 proteins in HUVECs were detected by
      Western blot. In addition, the mRNA expressions of miRNA-34a, SIRT1 and p53 in
      HUVECs were assayed by Real-time PCR. These results indicated that
      notoginsenoside R1 significantly reduced the positive staining rate of senescent
      cells, enhanced the cell proliferation capacity and intracellular SOD activity,
      decreased the proportion of cells in G0/G1 phase, and increased the percentage of
      cells in S phase simultaneously compared with the senescence model group.
      Moreover, notoginsenoside R1 decreased the mRNA expressions of miRNA-34a and p53
      and the protein expression of p53, p21 and p16.At the same time, notoginsenoside
      R1 increased the protein and mRNA expressions of SIRT1. The differences in these
      results between the senescence model group and the notoginsenoside R1 group were
      statistically significant(P<0.05). However, there was not statistically
      significant difference in these results between the notoginsenoside R1 group and
      the resveratrol group. In conclusion, the senescence of endothelial cells induced
      by H2O2 can be used as a model for studying aging. Notoginsenoside R1 has an
      obvious anti-aging effect on vascular endothelial cells in this study. The
      possible mechanism is that notoginsenoside R1 can delay the senescence process of
      vascular endothelial cells induced by H2O2 by regulating microRNA-34a/SIRT1/p53
      signal pathway.

PMID- 29600626
TI  - [Effects of Jinwu Jiangu recipe on IL-17/STAT3 signals in rheumatoid arthritis
      synoviocytes].
AB  - This paper aimed to investigate the effects of Jinwu Jiangu recipe total extract
      on the IL-17/STAT3 signals in rheumatoid arthritis synovial fibroblasts(RASF).
      The primary RASFs were cultured by tissue piece method in vitro, and divided into
      blank control group, Jinwu Jiangu recipe low dose group, Jinwu Jiangu recipe
      middle dose group, Jinwu Jiangu recipe high dose group, and tripterygium
      glycosides control group. They were then treated with corresponding serum free
      medium, different doses of Jinwu Jiangu recipe total extract(0.06, 0.6, 6.0 g.L
      1), and tripterygium glycosides(0.03 g.L-1) respectively for 24 hours. The gene
      expression levels of RORalpha, RORgammat, and STAT3 mRNA were detected by
      polymerase chain reaction(PCR), and the protein activity of IL-17R and pSTAT3
      were measured by Western blot assay. The results showed that as compared with
      blank control group, the expression levels of RORalpha, RORgammat, IL-17R and
      STAT3 mRNA in RASF were significantly declined(P<0.01). As compared with
      tripterygium glycosides control group, Jinwu Jiangu recipe total extract middle
      dose group and high dose group can down-regulate the expression levels of
      RORalpha, RORgammat, IL-17R and STAT3 mRNA(P<0.05), and the effect was more
      obvious in high dose group(P<0.01). As compared with blank control group, the
      protein expression levels of IL-17R and pSTAT3 in each treatment group were
      obviously decreased(P<0.01). As compared with tripterygium glycosides control
      group, Jinwu Jiangu recipe high dose group had more obvious effect in down
      regulating the protein expression of pSTAT3(P<0.01). Therefore, Miao medicine
      Jinwu Jiangu recipe total extract can down-regulate the expressions of RORalpha,
      RORgammat, and STAT3 mRNA, and inhibit the protein activity of IL-17R and pSTAT3
      in RASF.

PMID- 29600627
TI  - [Huaier aqueous extract inhibits proliferation of human hepatoma SK-HEP-1 cells
      through up-regulation of autophagy].
AB  - The purpose of this study was to investigate the effect of Huaier on autophagy of
      human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of
      SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the
      proliferation of SK-HEP-1 cells under different concentrations and different
      times. Acridine orange staining was used to measure the effect of Huaier on the
      autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to
      examine the effect of Huaier on the expression and distribution of autophagy
      marker LC3 in SK-HEP-1 cells. In addition, LC3 expression was also checked by
      immunoblot analysis in the presence of Huaier. At last, the effects of Huaier in
      combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK
      HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous
      extract significantly inhibited the proliferation of human hepatoma SK-HEP-1
      cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically
      promoted the formation of autolysosome in SK-HEP-1 cells. Moreover, Huaier
      markedly increased the number and intensity of intracellular LC3 fluorescent
      puncta and up-regulated LC3-II expression. These data indicated that Huaier
      evidently activated autophagy of SK-HEP-1 cells. Additionally, autophagy
      inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier
      treatment. Therefore, autophagy activation is involved in the inhibitory effects
      of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.

PMID- 29600628
TI  - [Effect of naringin on oxidative stress and endoplasmic reticulum stress in
      diabetic cardiomyopathy].
AB  - To explore the protective effect of naringin(Nar) on the injury of myocardium
      tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with
      oxidative stress and endoplasmic reticulum stress(ERS), the male SD rats were
      intraperitoneally injected with streptozotocin(STZ, 60 mg.kg-1) to establish the
      diabetic rat model and then randomly divided into the type 1 diabetic rat
      group(T1DR), the low-dose Nar group(Nar25), the middle-dose Nar group(Nar50) and
      the high-dose Nar group(Nar100). The normal rats were designed as control
      group(Con). Nar25, Nar50, Nar100 groups were orally administered with Nar at the
      doses of 25.0, 50.0, 100.0 mg.kg-1 per day, respectively, while the normal group
      and the T1DR group were orally administered with saline. At the 8th week after
      treatment, fasting plasma glucose and heart mass index were measured. The
      pathological changes in myocardial tissues were observed by microscope. The
      cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were
      measured. The gene and protein expressions of glucose-regulated protein
      78(GRP78), C/EBP homologous protein(CHOP), cysteinyl aspartate-specific
      proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to
      the results, compared with control group, the myocardial structure was damaged,
      the content of MDA was increased, while the activities of SOD were
      decreased(P<0.05) in T1DR group. GRP78, CHOP and caspase 12 mRNA and protein
      expressions were increased significantly in T1DR group(P<0.05, P<0.01). Compared
      with T1DR group, myocardial structure damage was alleviated in Nar treatment
      group. The content of MDA was decreased, while the activities of SOD were
      increased significantly. The mRNA and protein expressions of GRP78, CHOP and
      caspase 12 were increased, especially in middle and high-dose groups(P<0.05,
      P<0.01). After treatment with Nar for 8 weeks, myocardial structure damage was
      obviously alleviated in Nar treatment groups. The content of MDA was decreased,
      while the activities of SOD were increased significantly in myocardial tissues.
      The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased,
      especially in middle and high-dose groups(P<0.05, P<0.01). The findings suggest
      that Nar may protect myocardium in diabetic rats by reducing mitochondrial
      oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.

PMID- 29600629
TI  - [Effect of Zhenwu Tang on regulating of "AVP-V2R-AQP2" pathway in NRK-52E cells].
AB  - This study was aimed to investigate the effect and mechanism of Zhenwu Tang on
      AVP-V2R-AQP2 pathway in NRK-52E cells in vitro. Forty eight male SD rats were
      randomly divided into eight groups with 6 animals in each group. Distilled water
      or 22.68 g.kg-1.d-1 Zhenwu Tang(calculated by raw drug dosage meter) was given by
      gavage. Blood samples were collected by cardiac puncture, and the medicated serum
      was centrifuged from the blood by 3 000 r.min-1. NRK-52E cells were treated with
      different medicated serum or dDAVP. The condition of cell proliferation was
      detected by RTCA. The distribution of V2R and AQP2 in cells were detected by
      immunofluorescence. The expression of V2R, PKA and AQP2 were detected by Western
      blot and AQP2 mRNA level was detected by real-time PCR. Results showed that the
      level of AQP2 mRNA(P<0.01) and protein expression of V2R, PKA and AQP2(P<0.05,
      P<0.01, P<0.05) of Z7d group which was treated with Zhenwu Tang medicated serum
      for 24 h were significantly higher than that of normal rat serum group. And the
      expression level of V2R, p-AQP2 and AQP2(P<0.01, P<0.05, P<0.01) of Z7d+dDAVP
      group were significantly increased comparing to normal rat serum group. The
      results indicate that the applying of Zhenwu Tang medicated serum could increase
      the expression level of V2R, PKA and AQP2 which exist in AVP-V2R-AQP2 pathway in
      NRK-52E, and there is synergistic effect between Zhenwu Tang medicated serum and
      dDAVP. So the pathway of AVP-V2R-AQP2 may be one of the mechanism for which
      Zhenwu Tang regulate balance of water transportation.

PMID- 29600630
TI  - [Absorption of Inula cappa extract based on everted intestinal sac method].
AB  - To investigate the absorptive characteristics of Inula cappa extract based on the
      rat everted intestinal sac method in vitro. Nine representative ingredients in I.
      cappa extract were selected as the study objects. An UPLC-MS/MS method was
      established to determine and detect their cumulative absorption amount for
      expounding the absorptive characteristics of ingredients in different intestinal
      sections. According to the results, the transport mechanism of 8 compounds showed
      passive diffusion by the reverted gut sac method. And scopolin was actively
      transported in the intestine. The best absorption site of chlorogenic acid was
      duodenum. The best absorption site of cryptochlorogenic acid, 1,3-O
      dicaffeoylquinic acid, luteolin-7-glucoside and 3,4-O-dicaffeoylquinic acid were
      jejunum. The best absorption site of neochlorogenic acid, scopolin, 4,5-O
      dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid was ileum. The absorption
      of all the compounds was affected by pH and bile. All of the nine ingredients in
      I. cappa extract could be absorbed in intestines, but with differences in the
      absorption rate, the best absorptive site and mechanism, indicating that the
      intestinal absorption of I. cappa extract was selective.

PMID- 29600631
TI  - [Exploring Chinese medicine and Western medicine group modules in acute phase of
      ischemic stroke disease].
AB  - Under the theoretical guidance of "combination of disease and syndrome,
      correspondence between syndrome and prescription, and dynamic space-time", 11 135
      acute ischemic stroke patients were collected from hospital information
      system(HIS) of many 3A grade hospitals of traditional Chinese medicine. Complex
      network analysis was adopted to obtain the core syndrome elements in different
      periods of acute ischemic stroke patients, and it was found that the core
      syndrome elements were blood stasis syndrome, phlegm, endogenous wind, Yin
      deficiency, Qi deficiency, heat, hyperactivity of liver Yang, liver, and kidney
      of patients in hospital for the first day, and during 8-14 d in hospitalization,
      the core syndrome elements were blood stasis, phlegm, Yin deficiency, Qi
      deficiency, endogenous wind, hyperactivity of liver Yang, liver, and kidney. The
      data with "improved" and "cured" treatment outcomes were adopted for complex
      network analysis and correlation analysis to identify the Chinese and Western
      medicine group modules in patients with different disease conditions in different
      phases after hospitalization. It was found that the Chinese and Western medicine
      modules within 14 d after hospitalization mainly included "blood-activating and
      stasis-dissolving module "consisted by "anti-platelet drug + circulation
      improving medicine(or anticoagulant drug and anti-fibrinogen drug, et al) + blood
      activating and stasis-dissolving drugs", as well as "stasis-dissolving and phlegm
      reducing module" consisted by "anti-platelet drugs + circulation-improving
      medicine(or anticoagulant drug and anti-fibrinogen drug, et al) + phlegm
      refreshing drug". The core Chinese and Western medicine modules in patients with
      urgent and general conditions within 7 d after hospitalization mainly used "blood
      activating and stasis-dissolving module" and "stasis-dissolving and phlegm
      reducing module". Three or more Chinese medicine and Western medicines module
      with more than 1% utilization rate was not found in the patients with critical
      disease condition in admission. The urgent, general and critically ill patients
      in admission mainly used "blood-activating and stasis-dissolving module" in 8-14
      d. From the real world medical big data research, it was found that the combined
      use of Chinese and Western medicines were consistent with "combination of disease
      and syndrome, correspondence between syndrome and prescription, and dynamic space
      time" theory, and multiple multidimensional dynamic Chinese medicine and Western
      medicine group modules of "patient-syndrome-drug-time-effective" at the acute
      ischemic stroke stage were dug out, forming the method of Chinese and Western
      medicine combination research based on electrical medical big data.

PMID- 29600632
TI  - [Response to US review rules on patent subject matter of traditional Chinese
      medicine compositions].
AB  - The United States Patent and Trademark Office(USPTO) issued Interim Guidance on
      Patent Subject Matter Eligibility on December 16, 2014, bringing certain effects
      to the review rules on patent application of Chinese medicine compositions. Based
      on the Interim Guidance, cases analysis was used in this paper to analyze the
      patent subject matter issues of traditional Chinese medicine compositions in the
      United States. The researches have shown that the application documents should be
      properly written in the United States when the patent for Chinese medicine
      compositions is applied, which can improve the probability of authorization.

PMID- 29600633
TI  - [Herbal textual research on Chinese medicine "Huangjing" (Polygonati Rhizoma)and
      some enlightenments].
AB  - To clarify the change and development of the original plants, medicinal organs,
      traditional functions, resource distribution of "Huangjing"(Polygonati Rhizome),
      a traditional Chinese medicine, we investigated Polygonatum species on the
      ancient Chinese herbal texts. The name of "Nuwei" was first carried out in the
      book of Sheng Nong's Herbal Classic. Its effects included two aspects: one was
      similar to "Weirui"(Polygonati Odorati Rhizome, "Yuzhu"), that was tonifying,
      nourishing one's vitality, removing wind and dampness, settling five organs,
      making body lightness, keeping longevity and not being hungry; the second was
      alike to "Huangjing" recorded in the book of Ming Yi Bie Lu(Appendant Records of
      Famous Physicians). Specifically, "Weirui" possesses the therapeutic effect of
      "Nuwei", while "Huangjing" possesses the tonic effect of " Nuwei". Thereafter,
      the following ancient Chinese herbal texts kept those two names and function
      records. Accordingly, we hold the point of view that "Huangjing" was first
      carried out in the book of Sheng Nong's Herbal Classic in the synonym of "Nuwei".
      "Yuzhu" included the "Huangjing" in ancient herbal text before Qing Dynasty, that
      was further confirmed by the research on change and development of the original
      plants. The identification between "Yuzhu" and "Huangjing" was based on the shape
      of rhizome and size before early Tang Dynasty. The shape was a key character and
      used up to now, but size was not reasonable. The opposite phyllotaxy was an
      important character of authentic "Huangjing" from Tang to Qing Dynasty. The
      seedling of Polygonatum sibiricum and P. kingianum, the adult plant of P.
      cyrtonema with alternate leaves were misused as "Yuzhu"("Nuwei" and "Weirui") at
      that time. Therefore, both "Yuzhu" and "Huangjing" should be used as key words
      during the search of ancient prescriptions and development of new drugs and
      health foods. The leaves, flowers, fruits and seedlings could be used as food or
      medicine other than the rhizomes in ancient China, but they haven't been
      developed in modern times. The culture of "Huangjing" had a long history starting
      with Tang Dynasty, which was recorded in Tang poetry. Then in Ming Dynasty, the
      culture method was described in Compendium of Materia Medica, that was cutting
      the rhizomes into 2 feet, planting sparsely(they would be grown densely in the
      next year), or sowing the seeds. The harvesting and processing were first
      recorded in Ming Yi Bie Lu: "harvest the roots in February, dry in the shade".
      Then the processing method was changed to "steaming and drying in the sun,
      repeatedly for nine times" in Shi Liao Ben Cao(Dietetic Materia Medica) and
      "harvesting in August as well" in Ben Cao Tu Jing(Commentaries on the
      Illustrations). No breakthrough has been taken in the breeding of cultivars and
      key cultivation technologies yet. As to the geo-authentic habitats, Mount
      Songshan and Maoshan were firstly recorded as the best producing areas of
      "Huangjing" in Ben Cao Tu Jing. But Maoshan, Jiangsu province and Mount Songshan,
      Henan province, are not main producing areas in modern China. Consequently, the
      plantation plan of Polygonati Rhizome needs further study.

PMID- 29600634
TI  - [Medicinal research progress on pig bile and overview of its quality control].
AB  - In this paper, herbal records and studies on pharmacological activity and
      chemical component of pig bile were reviewed for a systematic and comprehensive
      summary about this traditional Chinese medicinal material. Beyond that, not only
      national standards but also local standards for the quality control of pig bile
      were analyzed and summarized. It is indicated that this traditional Chinese
      medicinal material has a broad medicinal prospect, and the standards for quality
      control should be revised and improved.

PMID- 29600635
TI  - [Identification of bear bile powder and its adulterants by using DNA barcoding
      technology].
AB  - To identify the precious bile powder and its adulterants by DNA barcoding, and
      establish its standard experimental process to ensure the safe and effective
      utilization. Total twelve sequences from samples of bear bile powder which come
      from Ursus thibetanus for DNA extraction, PCR(polymerase chain reaction) and
      sequence, then using CodonCode Aligner V 7.0.1 shear primer region to obtain COI
      sequence. The COI sequences of U. arctos and their adulterants were obtained from
      GenBank. MEGA7.0 software was applied for analyzing mutation, calculating
      intraspecific and interspecific K2P(Kimura 2-Parameter) genetic distance and
      constructing the Neighbor-joining tree(NJ). The results showed that the maximum
      K2P genetic distance of bear bile powder of U. thibetanus and U. arctos are far
      less than minimum K2P genetic distance within its adulterants species, and the
      results of NJ tree demonstrated that each species could be distinguished from the
      counterfeits obviously. DNA barcoding is a safe, convenient and reliable
      technique for species identification, and it is important to establish the
      standard sequence of COI sequences for animal medicines.

PMID- 29600636
TI  - [Study of characteristic ions in frequently-used traditional Chinese medicinal
      materials derived from animal bile and its application].
AB  - A LC-MS method was established for study of characteristic ions in frequently
      used traditional Chinese medicinal materials derived from animal bile. UPLC-Q-TOF
      was used in the data acquisition work, then, the software of MarkerLynxTM v.4.1
      was performed in the chemometric analysis of data. Besides, selected ion
      chromatograms of these bile acid ions were comparative studied. Better results
      were gained in the specificity identification of pig bile, bear bile, cultivated
      cow-bezoar in vitro, artificial cow-bezoar and some compound preparations(Hugan
      tablet and Rengongniuhuang Jiaxiaozuo capsule) by this method. The method is
      suitable for the specificity identification of pig bile, bear bile, cultivated
      cow-bezoar in vitro, artificial cow-bezoar and compound preparations containing
      these medicinal materials.

PMID- 29600637
TI  - [Multi-component quantitation of artificial cow-bezoar and study on its markers
      of quality difference].
AB  - An HPLC-ELSD method for quantitation of GCANa, CA, HDCA, CDCA and DCA in
      artificial cow-bezoar was developed in this study. The chromatographic separation
      was performed using a Wondasil CC18(4.6 mmchi250 mm,5 MUm) column at a column
      temperature of 25  degrees C and liquid flow-rate of 1.0 mL.min-1. Acetonitrile
      and 0.2% formic acid solution were used as mobile phase with a linear gradient
      and injection volume was 10 MUL. An ELSD was used with a nitrogen flow-rate of
      2.3 L.h-1at a drift tube temperature of 110  degrees C. Some chemometric methods
      were applied in data procession and analysis for exploration of the markers of
      quality difference. The accurate and simple method is suitable for the quality
      evaluation and the quality control of artificial cow-bezoar.

PMID- 29600638
TI  - [Contamination distribution and control measures of aflatoxins in Chinese herbal
      pieces].
AB  - As an important part of traditional medicine in China, traditional Chinese
      medicine(TCM) plays a significant role because of its unique medical efficiency,
      less adverse reactions and extensive resources. However, in recent years, the
      aflatoxins in medicinal herbs have been detected excessive both at home and
      abroad, seriously affecting the reputation and credibility of traditional Chinese
      medicine. In this paper, the current status of aflatoxins contamination in
      medicinal herbs was analyzed, and the internal and external factors of aflatoxins
      contamination in traditional Chinese medicine were also summarized. In view of
      the high toxicity of aflatoxins, it is proposed to strengthen the mildew
      prevention and control from the early planting to storage stage, and the
      reasonable detoxification mode should also be considered. This review aims to
      provide a reference in guaranteeing the clinical safe administration of medicinal
      herbs and reducing the risk of being poisoned by aflatoxins.

PMID- 29600639
TI  - [Application of DNA molecular marker technologies in study of medicinal Physalis
      species].
AB  - As traditional Chinese medicinal herbs, Physalis plants have a variety of
      pharmacological activities, such as anti-inflammatory, anti-oxidant, and anti
      cancer effects, and have been used for the treatment of malaria, rheumatism,
      hepatitis, asthma, and cancer. In addition to the medicinal value, many Physalis
      species are also the high-grade nutrition health care fruits, can be made canned
      and candied etc. In the study, the application progress of DNA molecular marker
      technologies in medicinal Physalis plants in recent years was reviewed, in order
      to provide an important molecular technical basis for the identification,
      classification and rational development and protection of medicinal Physalis
      resources.

PMID- 29600640
TI  - [Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of
      compatibility].
AB  - ABC efflux proteins are a kind of transporters mediating diversified endogenous
      and exogenous efflux protein substrates across the plasma membrane by depending
      on the chemical energy released by ATP hydrolysis. As a vitally important
      functional membrane, it is widely found in various tissues and organs. The drug
      changes the expressions and/or functions of the transport proteins, which will
      affect the disposal process of substrate drugs corresponding to transporters in
      vivo, and finally lead to the pharmacokinetic interactions. The efflux proteins
      take part in the absorption, distribution, metabolism and excretion of drugs, and
      mainly consist of P-glycoprotein(P-gp), multidrug resistance associated
      protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or
      inhibition effect of drugs on efflux protein plays a greatly significant role in
      the drug interaction produced by the compatibility of traditional Chinese
      medicine, which may be one of the important mechanisms of the theory of seven
      features of compatibility. In this article, the effects of seven features of
      compatibility on the ABC efflux transporters were reviewed, in order to reveal
      the roles of efflux protein in the herb-pairs compatibility, and provide new
      ideas for the mechanism and rationality of herb compatibility.

PMID- 29600641
TI  - [Advance in studies on pharmacokinetics of baicalin].
AB  - Scutellariae baicalensis is one of the most important traditional Chinese
      medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has
      significant pharmacological effects such as antimicrobial activity, anti
      inflammatory and antioxidation. Baicalin is one of its main effective components.
      However, baicalin's low bioavailability has restricted its clinical application.
      In recent decades, extensive studies have been carried out on the metabolism of
      baicalin in vivo at home and abroad. In order to provide scientific references
      for baicalin's further studies, this paper would not only review the advances in
      pharmacokinetics research of baicalin and Chinese herbal preparations containing
      baicalin, but also make a summary on research status of baicalin.

PMID- 29600642
TI  - [Development and research advance of pharmacognosy field based on CNKI].
AB  - Based on the literature data in CNKI, data mining and analysis technologies were
      used in this paper to describe the scientific research and development direction
      of Pharmacognosy in the last decade from the perspective of bibliometrics. The
      analysis of measured data revealed the core research institutions, excellent
      research teams, leading scholars, major research aspects and research progress in
      the field. Results showed that most of the scholars in the field were from
      colleges and institutions, accounting for 74.6% of the total research findings
      and forming a group of core scholars. In terms of frequency and timeliness of
      citation, pharmacognosy is a discipline in sustained growth and development since
      it mainly cites the literature in the other disciplines, absorbs and utilizes
      knowledge of the other disciplines. Over the last few years, molecular
      identification and genetic diversity have become the research hotspots in
      pharmacognosy, and the techniques and methods such as ISSR, RAPD, DNA barcoding
      and DNA molecular marker have been widely used.

PMID- 29600643
TI  - [Study on original investigation, macroscopic and microscopic identification of
      pharmacopoeia contained species of Epmedii Folium].
AB  - Epimedii Folium is a commonly used traditional Chinese drug, and now still
      depends on the wild resource. In recent years, with the surge in consumption, the
      resources are declining, the use of market varieties are constantly changing. In
      this paper, Production and sales situation of the five species contained in
      pharmacopoeia(Epimedium brevicornu, E. sagittatum, E. pubescens, E. koreanum and
      E. wushanense) have been studied on the basis of the existing researches, in
      depth investigation and collection of accurate plant specimens and samples. And
      the origins of Epimedii Folium regulated by the pharmacopoeia have been
      discussed. At the same time, more exclusive and practical features have been
      summarized on the basis of observation and comparison with the stereo, optical
      and stereo-fluorescence microscopy technologies, and refering the related
      literatures on leaf structure and anatomy.The results of this study will provide
      a useful reference for the clinical medication, supervision, inspection, and
      standard drafting and so on.

PMID- 29600644
TI  - [Gene cloning and prokaryotic expression of glycosyltransferase from Ligustrum
      quihoui].
AB  - According to the previous results from transcriptome analysis of Ligustrum
      quihoui, a glycosyltransferase gene(xynzUGT) was cloned by rapid amplification of
      cDNA ends(RACE). The full length cDNA of xynzUGT was 1 598 bp, consisting of 66
      bp 5'-UTR, 1 440 bp ORF and 92 bp 3'-UTR. The ORF encoded a 480 amino-acid
      protein(xynzUGT) with a molecular weight of 54 826.67 Da and isoelectric point of
      5.82. The structure of enzyme was analyzed by using bioinformatics method, the
      results showed that the primary structure contained a highly conserved PSPG box
      of glycosyltransferase, the secondary structure included alpha helix(38%), beta
      sheet(12.1%) and random coil(49.9%), and tertiary structure was constructed by
      peptide chain folding to form two face-to-face alpha/beta/alpha domains(often
      referred to as a Rossmann domains), between which a substrate binding pocket is
      sandwiched. The phylogenetic tree analysis indicated that xynzUGT might catalyze
      glycosylation of phenylpropanoids, such as tyrosol. Further simulation experiment
      of molecular docking between enzyme and tyrosol showed that Gly138 and Ser285
      located in the binding pocket interacted with tyrosol by hydrogen bonding. SDS
      PAGE analysis exhibited that the prokaryotic expression system successfully
      expressed recombinant xynzUGT with molecular weight of 58 370.57 Da, but it
      exists in the form of non-soluble inclusion bodies. Using the molecular chaperone
      and enzyme co-expression method, the soluble expression was promoted to some
      extent. The above works laid the foundation for further studying on enzymatic
      reaction in vitro and clarifying the functional mechanism of enzyme.

PMID- 29600645
TI  - [Clone and expression of CpGAPDH gene in Codonopsis pilosula].
AB  - GAPDH(glyceraldehyde-3-phosphate dehydrogenase) gene is a key enzyme gene in
      carbohydrate metabolism and always used as reference gene. To clarify and
      complete the biosynthetic pathway of polysaccharide, the GAPDH gene in Codonopsis
      pilosula, named CpGAPDH, was cloned according to the transcriptome of pilosula,
      using the GAPDH gene in potato as query. The CpGAPDH contained a 1 014 bp open
      reading frame(ORF) and encoded a protein with 337 amino acids. Bioinformatic
      analysis clearly suggested that CpGAPDH shared high similarity with GAPDH among
      other plants, and had the closest relatives to potato and danshen. The predicted
      protein did not have signal peptide, which indicated that it might be located in
      the cytoplasm. According to the existing of several phosphorylation sites and the
      conserved domains analysis, we predicted that it belonged to Gp_dh_N superfamily.
      Prokaryotic expression showed that the recombinant expressed a 44.3 kDa protein,
      which was corresponding to the theoretical relative molecular mass. However, the
      relative transcript level of the CpGAPDH did not have significant differences in
      different tissues and roots at different developmental stages of pilosula.
      Moreover, the stability of the CpGAPDH was analyzed by BestKeeper, geNorm, and
      NormFinder and RefFinder software, which showed that the CpGAPDH was more stable
      and could be used as a new reference gene. All these lay a foundation for the
      expression analysis of the gene relative to the polysaccharide synthesis.

PMID- 29600646
TI  - [Bioinformation analysis of chorismate synthase in Baphicacantus cusia and other
      78 species of plants].
AB  - Chorismate synthase(CS, EC:4.2.3.5) catalyses 5-enolpyruvy-shikimate-3-phosphate
      to form chorismate, which is the essential enzyme for chorismate biosynthesis in
      organisms. The amino acid sequences of CS from 79 species of higher plants were
      reported in GenBank at present. 125 amino acid sequences of CS from
      Baphicacanthus cusia and other 78 species of plants were predicted and analyzed
      by using various bioinformatics software, including the composition of amino acid
      sequences, signal peptide, leader peptide, hydrophobic/hydrophilic, transmembrane
      structure, coiled-coil domain, protein secondary structure, tertiary structure
      and functional domains. The phylogenetic tree of CS protein family was
      constructed and divided into eight groups by phylogenetic analysis. The homology
      comparison indicated that B. cusia shared a high homology with several plants
      such as Sesamum indicum, Nicotiana tabacum, Solanum tuberosum and so on. The open
      reading frame(ORF) of all samples is about 1 300 bp, the molecular weight is
      about 50 kDa, the isoelectric point(pI) is 5.0-8.0 which illustrated that CS
      protein is slightly basic. The ORF of CS we cloned in B. cusia is 1 326 bp, the
      amino acid residues are 442, the molecular weight is 47 kDa and pI is 8.11. The
      CS in B.cusia showed obvious hydrophobicity area and hydrophilicity area, no
      signal peptide, and may exists transmembrane structure areas. The main secondary
      structures of CS protein are random coil and Alpha helix, also contain three main
      structural domains which are an active structural domain, a PLN02754 conserved
      domain and a FMN binding site. The acquired information in this study would
      provide certain scientific basis for further study on structure-activity
      relationship and structure modification of CS in plants in the future.

PMID- 29600648
TI  - [Identification and preparation of a glycol-protein fraction AN from tea extracts
      and its in vivo and in vitro anti-hyperglycosemia activity].
AB  - The present study compared active ingredients of tea from different sources to
      select tea type and the fraction of tea extracts for the highest anti
      hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected
      tea extract. Tea extracts were separated and enriched by molecular weight using
      ultra-filtration technology. The extracts were first screened by alpha
      glucosidase inhibition assay, followed by using a rat inverted intestine sac
      system to measure the effect on glucose transport. Both alloxan-induced diabetic
      rat model and high-fat diet combined with streptozotocin-induced rat diabetes
      mellitus model were used to study the effects of active components on blood
      glucose, body weight, insulin resistance. The experimental results showed that
      the different kinds of tea extracts had different inhibitory effects on alpha
      glucosidase, and the inhibitory effect of tea extract E on alpha-glucosidase was
      stronger. The effects of different components of tea extract E also varied
      greatly, of which Fraction AN protein had stronger inhibitory effect on alpha
      glucosidase than other fragments, and Fraction AN protein had a strong inhibitory
      effect on glucose transport, reduced blood sugar and normalized insulin secretion
      in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the
      extracts might be responsible for the anti-hyperglycemic activity of tea
      polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on
      both alpha-glucosidase activity and glucose transport by the small intestine. It
      also reduced blood glucose level and normalized insulin secretion in diabetic
      rats, and has a protective effect on diabetic rats.

PMID- 29600647
TI  - [Effect of paeoniflorin and menthol on membrane fluidity, Na+-K+-ATPase activity
      and Ca2+-ATPase activity during transport of puerarin in Calu-3 cell].
AB  - The aim of this research is to investigate the effects of paeoniflorin and
      menthol on the physiological function of Calu-3 cell membrane during the
      transport of puerarin. Calu-3 cell was used as the in vitro cell model to
      simulate nasal mucosa tissues, and the cell membrane fluidity, Na+-K+-ATPase
      activity and Ca2+-ATPase activity were detected by fluorescence recovery after
      photobleaching(FRAP) and ultramicro enzyme activity testing, in order to explore
      the mechanism of compatible drugs on promoting puerarin transport. The results
      showed that when puerarin associated with low, middle and high concentration of
      menthol or both paeoniflorin and menthol, the fluorescence recovery rate was
      increased significantly, while Na+-K+-ATPase activity had no significant change
      and Ca2+-ATPase activity was enhanced significantly as compared with puerarin
      alone. Therefore, it was concluded that menthol had the abilit? of promoting the
      transport and the mechanism might be related to increasing membrane fluidity and
      activating Ca2+-ATPase.

PMID- 29600649
TI  - [Quantitative determination method and application of pharmaceutical adjuvant
      tween 80].
AB  - Based on the fact that chromogenic reaction of blue complex, a reaction product
      which can be dissolved in organic solvents, can be realized by polyethoxy and
      ammonium thiocyanate in tween 80, a rapid and accurate way for the determination
      for tween 80 in pharmaceutical adjuvant was established in this study, providing
      reliable technical means for quality control of traditional Chinese medicine
      injections. Based on the study of reaction kinetics, chromogenic reaction
      temperature and time, as well as extraction of organic solvents and other key
      conditions were optimized, and Kumu injection was used as the test material for
      method validation and applicability investigation. It was finally determined that
      3 mL ammonium thiocyanate solution was added in the sample solution, and the
      reaction was carried out in a boiling water bath for 2 h. After cooling to room
      temperature, 5 mL of dichloromethane was added to extract the chromogenic
      product. The absorbance value was measured at the wavelength of 623 nm to
      calculate the tween 80 content in the sample. Under optimized conditions, tween
      80 solution showed a good linear relationship with the absorbance in the range
      from 0.8 mg to 3.0 mg. The linear regression equation was y=0.258x-0.047. The
      correlation coefficient r was 0.999 6. Under the experimental conditions, the
      average recovery was 99.66%, and the precision RSD was less than 2.0%. The
      results showed that this method can quickly and accurately determine the content
      of tween 80 in Kumu injection, and it could be applicable to the quality control
      of traditional Chinese medicine injections.

PMID- 29600650
TI  - [Efficient discovery and capturing of nNOS-PSD-95 uncouplers from Trifolium
      pratense].
AB  - Magnetic molecularly imprinted polymers(MMIPs) were prepared with ZL006 as
      template, acrylamide(AA) as the functional monomer, and acetonitrile as pore
      forming agent; then Fourier transform infrared spectroscopy(FT-IR) and scanning
      electron microscopy(SEM) were used to characterize their forms and structures.
      Simultaneously, the MMIPs prepared previously were used as sorbents for
      dispersive magnetic solid phase extraction(DSPE) to capture and identify
      potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the
      activities of the screened compounds were evaluated by the neuroprotective effect
      and co-immunoprecipitation test. The experiment revealed that the successfully
      synthesized MMIPs showed good dispersiveness, suitable particle size and good
      adsorption properties. Formononetin, prunetin and biochanin A were separated and
      enriched from Trifolium pratense by using the MMIPs as artificial antibodies and
      finally biochanin A was found to have higher cytoprotective action and uncoupling
      action according to the neuroprotective effect and co-immunoprecipitation test.

PMID- 29600651
TI  - [Trace phenolic compounds from Red Yeast Rice].
AB  - Trace chemical constituents from the ethyl acetate extract of Red Yeast Rice were
      investigated. Four phenolic compounds were isolated by various column
      chromatographies, and their structures were identified on the basis of
      spectroscopic analysis including UV, MS, IR and NMR. The four compounds were
      identified as 2-methyl-5-(2'R-methyl-4'-hydroxy-butyl)-cinnamic acid(1), 5-(2'
      hydroxy-6'-methyl phenyl)-3-methylfuran-2-carboxylic acid(2), daidzein(3), and
      genistein(4). Compound 1 was new and 2 was firstly discovered from the genus
      Monascus, while 3-4 were obtained from Red Yeast Rice for the first time.

PMID- 29600652
TI  - [Study on antioxidant activity of flavonoids from leaves of Psidium guajava].
AB  - The present study is to study the chemical constituents from ethanol extract of
      Psidium guajava leaves. The constituents were separated and purified by silica
      gel column chromaiographios over, macroporous resin D-101, Sephadex LH-20, and
      ODS. Six flavonoids compounds were isolated and identified as quercetin(1),
      quercetin-3-O-alpha-D-arabinopyranoside(2), quercetin-3-O-alpha-D
      ribopyranoside(3), quercetin-3-O-beta-D-galactopyranoside(4), quercetin-3-O-alpha
      D-glucopyranoside(5), and quercetin-3-O-alpha-D-xylpyranoside(6). The antioxidant
      effects of six flavonoids was evaluated by scavenging ability of DPPH, superoxide
      anion, ABTS.+, and reducing effect of Fe3+ as well as total antioxidant
      capacity(FRAP). Vitamin C was used as positive control. The results indicated
      that six flavonoids exhibited significant antioxidant effects.

PMID- 29600653
TI  - [Content determination of four diester diterpenoid alkaloids in leaves of
      Aconitum kusnezoffii by HPLC].
AB  - This present study is to develop an HPLC method for simultaneous determination of
      four diester diterpenoid alkaloids, beiwutine, mesaconitine, hypaconitine and
      aconitine in the leaves of Aconitum kusnezoffii, so as to provide evidence of the
      quality control of this herb. The four constituents were measured on a Waters
      XBridge CC18 column(4.6 mmchi250 mm, 5 MUm). The mobile phase was acetonitrile-40
      mmol.L-1 ammonium acetate solution(adjusted pH to 10.5 with ammonia
      solution)(33:67) with isocratic elution at a flow rate of 1.0 mL.min-1; the
      detection wavelength was 235 nm; the column temperature was 30  degrees C, and
      the injection volume was 10 MUL. Next, this contents of the four diester
      diterpenoid alkaloids in 12 samples were 0.025 5-0.088 5, 0.039 1-0.071 5, 0.026
      6-0.081 0 and 0.008 12-0.031 2 mg.g-1, respectively. Next, this method has been
      successfully applied to the analysis of A. kusnezoffii folium in different
      harvest periods. The contents of the four alkaloids decreased primarily, and then
      increased with the postponing of harvest. The established method is proved to be
      accurate and sensitive for the determination of alkaloids in A. kusnezoffii
      folium, and may be useful for the quality improvement of this herbal medicine.
      Moreover, these results indicated the scientific significance for the toxicity
      and the suitable harvest time of this herb.

PMID- 29600654
TI  - [Artesunate inhibits proliferation of glioblastoma cells by arresting cell
      cycle].
AB  - Glioblastoma is a common brain tumor and the overall survival rate of the
      patients is very low, so it is an effective way to develop the potential
      chemotherapy or adjuvant chemotherapy drugs in glioblastoma treatment. As a well
      known antimalarial drug, artesunate(ARTs) has clear side effects, and recently it
      has been reported to have antitumor effects, but rarely reported in glioblastoma.
      Different concentrations of ARTs were used to treat the glioblastoma cells, and
      then the inhibitory effect of ARTs on glioblastoma proliferation was detected by
      MTT assay; Ki67 immunofluorescence assay was used to detect the proliferation of
      cells; Soft agar experiment was used to explain the clonal formation abilities in
      vitro; Flow Cytometry was used to detect the cell cycle; and Western blot assay
      was used to determine the expression of key cell cycle protein. MTT assay results
      indicated that ARTs-treated glioblastoma cell A172, U251, U87 were significantly
      inhibited in a time-and-dose dependent manner as compared to the control
      group(DMSO treatment group). Soft agar experiment showed that ARTs could
      significantly reduce the clonal formation ability of glioblastoma. Furthermore,
      Flow cytometry analysis showed that ARTs could obviously increase the cell
      proportion in G0/G1 phase and reduce the cell proportion in S phase. Western blot
      results showed that the expressions of cell cycle-related proteins CDK2, CDK4,
      cyclin D1 and cyclin B1 were all obviously down-regulated. Above all, ARTs may
      inhibit the proliferation of glioblastoma cells by arresting cell cycle in G0/G1
      phase through down-regulating the expression of CDK2, CDK4, cyclin D1, cyclin B1.
      These results may not only provide a novel method for rediscovering and reusing
      ARTs but also provide a new potential drug for treating glioblastoma.

PMID- 29600655
TI  - [Exploration on antibacterial activity and mechanism of flowers and leaves from
      Paeonia rockii based on network pharmacology].
AB  - This paper aimed to investigate the antibacterial activity of flowers and leaves
      from Paeonia rockii, screen antibacterial compounds and predict targets of
      antibacterial to explore its multi-component, multi-target antibacterial
      mechanism. In this study, minimal inhibitory concentration(MIC) of seven strains
      of Staphylococcus aureus, S. epidermidis, Bacillus subtilis, B. cereus,
      Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were
      determined by microdilution method. Uniprot databases was used to find the
      antibacterial targets, and RCSB was used to identify targets associated with
      antimicrobial activity as docked receptor proteins. The candidate active
      ingredients from flowers and leaves of P. rockii were identified by database such
      as PubChem. The ligands were constructed by ChemDraw, Avogadro and Discovery
      Studio Visualizer. QuickVina 2.0 software was used to molecular docking. Besides,
      the Cytoscape 3.5.1 software was used to construct activity compounds of flowers
      and leaves from P. rockii ingredients-targets network, and Uniprot software was
      used to analyze gene ontology and KEGG pathway. In vitro antibacterial
      experiments found antibacterial effect of the flowers and leaves from P. rockii,
      especially methanol extraction of flowers has the strongest antibacterial effect.
      The network pharmacology indicated that total 29 activity ingredients and their
      18 targets were screened in flowers and leaves from P. rockii. Comparison of the
      active ingredients and the number of antimicrobial target networks, it is
      predicted that the antibacterial components are mainly flavonoids and phenolic
      acids and main mechanism of antibacterial is to inhibit the synthesis of
      bacterial proteins. In this study, potential antibacterial activity of flowers
      and leaves from P. rockii has be found by antibacterial experiments in vitro and
      network pharmacology screening. And this study provides new clues for further
      basic study on the antibacterial agents of flowers and leaves from P. rockii.

PMID- 29600656
TI  - [Characterization and pathophysiological changes of cerebral infarction rat model
      with qi-deficiency and blood-stasis Syndrome].
AB  - This study aimed to observe the general state and changes in pathophysiological
      indexes of multiple cerebral infarction rat model with Qi-deficienty and Blood
      stasis syndrome. Rats were randomly divided into 4 groups(with 30 in each group):
      the normal group, the sham group, the model group and the Yiqi Huoxue recipe
      group. Rats in the model group and Yiqi Huoxue group were provided with
      interruptable sleep deprivation for 7 days before the multiple cerebral
      infarction operation, and followed by another 4 weeks of sleep deprivation; rats
      in the Yiqi Huoxue group were intragastrically administrated with drug at a dose
      of 26 g.kg-1, once a day for 4 weeks. The general state was observed, and the
      pathophysiological indexes were measured at 48 h, 2 weeks and 4 weeks after
      administration. The results showed that rats in the normal group and the sham
      group represented a good general state and behaviors, with a normal morphological
      structure of brain tissues; rats in the model group featured yellow fur,
      depression, accidie, loose stools and movement disorder, with obvious brain
      histomorphological damage, which became aggravated with the increase of modeling
      time; rats in the Yiqi Huoxue group showed release in the general state and above
      indexes. Compared with the sham group at three time points, rats in the model
      group showed decrease in body weight, exhaustive swimming time and RGB value of
      tongue surface image, and increase in whole blood viscosity of the shear rate
      under 5, 60 and 150 S-1, reduction in cerebral cortex Na+-K+-ATPase, Ca2+-ATPase
      activity and contents of 5-HT, rise in TXB2 levels and decline in 6-keto-PGF1a in
      serum(P<0.05, P<0.01). Compared with the model group, rats in the Yiqi Huoxue
      group showed alleviations in the above indexes at 2 w and 4 w(P<0.05, P<0.01).
      The results showed that the characterization and pathophysiological indexes in
      the multiple cerebral infarction rat model with Qi-deficiency and blood-stasis
      syndrome were deteriorated; Yiqi Huoxue recipe could significantly alliviate the
      abnormal conditions, which suggested of the model was stable and reliable and the
      pathophysiologic evolutionary mechanism might be related to energy metabolism
      dysfunction, vasoactive substance abnormality and changes in neurotransmitters.

PMID- 29600657
TI  - [Effect of leech on lipid metabolism and liver in hyperlipidemia rats].
AB  - To explore the effect of leech on lipid metabolism and liver function in
      hyperlipidemia rats and the possible mechanism, biochemical analyzer was used to
      examine the regulation of leech on levels of serum triglycerides(TG), total
      cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and high-density
      lipoprotein cholesterol(HDL-C). The levels of ALT and AST in serum were detected
      by ELISA. The proteins expression of ACAT-2, Fas and HMGCR in liver tissue was
      detected by Western blot. The weight of body and liver were weighed, and liver
      index was calculated. Oil red O staining was used to observe the lipid
      accumulation in liver tissue of rats by light Microscope. The results showed that
      leech could decrease the levels of TC, LDL-C obviously, and increase HDL-C,
      decrease the levels of ALT, AST and the liver index, down-regulate the proteins
      expression of ACAT-2, Fas and HMGCR. And oil red O staining indicated that the
      lipid accumulation was less in the liver tissue of the rats intervented by leech.
      These data indicated that leech may affect the expression of ACAT-2, Fas and
      HMGCR in liver tissue to reduce the synthesis of cholesterol and fatty acid, and
      promote the cholesterol transforming, then regulate lipid metabolism to decrease
      the levels of serum lipid, and reduce lipid accumulation in liver tissue and ease
      liver injury of rats, then slowing down the process of nonalcoholic fatty liver
      disease(NAFLD) in hyperlipidemia rats.

PMID- 29600658
TI  - [Protective effect of Dendrobium candidum on isoproterenol induced cardiac
      hypertrophy in rats].
AB  - To study the effect and mechanism of Dendrobium candidum on isoproterenol-induced
      myocardial hypertrophy in rats, 60 healthy SD rats(30 males and 30 females) were
      randomly divided into 5 groups(12 in each group): normal group, model group,
      three D. candidum preventive administration groups(0.09, 0.18, 1.1 g.kg-1).
      Except for the normal group, rats of other groups were injected back
      subcutaneously with ISO(5 mg.kg-1) for 10 consecutive days. At the same time,
      preventive administration groups began to give different doses of the sample for
      30 days and model group began to give normal saline. Left ventricular systolic
      pressure(LVSP) was measured in each group by common carotid artery cannulation,
      and the left ventricle(LW)/tibia length, heart weight index(HWI) and myocardial
      hydroxyproline(Hydro) content were calculated. Myocardial tissue HE staining and
      Masson staining were used to observe the myocardial structure and the degree of
      myocardial fibrosis respectively. Atrial natriuretic peptide(ANP), brain
      natriuretic peptide(BNP), and cardiac troponin I(cTN-I) concentration were
      measured by enzyme-linked immunosorbent assay(ELISA). The results showed that as
      compared with the normal group, the levels of ANP, BNP and cTN-I in plasma were
      significantly increased in ISO-induced hypertrophic rats; as compared with the
      model group, D. candidumcan inhibit ISO-induced ventricular pressure and
      ventricular hypertrophy, reduce myocardial collagen synthesis, improve myocardial
      fibrosis and ventricular remodeling, and significantly down-regulate ANP, BNP and
      cTN-I levels in plasma. This study shows that D. candidum has a protective effect
      on isoproterenol-induced cardiac hypertrophy.

PMID- 29600659
TI  - [Astragalus polysaccharide may increase sensitivity of cervical cancer HeLa cells
      to cisplatin by regulating cell autophagy].
AB  - This study aimed to investigate the possible sensitivity of Astragalus
      polysaccharides, in order to improve the chemosensitivity of cervical cancer HeLa
      cells to cisplatin by regulating the cell autophagy, and explore its possible
      mechanism. In this study, HeLa cells were divided into control group, cisplatin
      group, Astragalus polysaccharide group, and Astragalus polysaccharide combined
      with cisplatin group. MTT assay was used to detect the proliferation of cervical
      cancer HeLa cells. Flow cytometry was used to detect the apoptosis and cycle of
      HeLa cells in each experimental group. RT-PCR was used to detect the mRNA
      expression of autophagy-related proteins beclin1, LC3II and p62. The expression
      levels of autophagy-related proteins beclin1, LC3II, LC3I and p62 were detected
      by WB method. MTT results showed that compared with the control group, the
      proliferation of HeLa cells was significantly inhibited in each administration
      group(P<0.05), and the inhibitory effect of the combination group was more
      significant(P<0.01). The apoptotic rate of HeLa cells was significantly
      increased(P<0.05), and the apoptotic rate of the combination group was
      significantly increased(P<0.01) compared with the control group(P<0.05).In
      conclusion, G0/G1 phase showed the most significant differences between the two
      groups. RT-PCR and WB results showed that the gene and protein expressions of
      beclin1 and LC3II were up-regulated, while the gene and protein expressions of
      p62 were down-regulated compared with the control group. The above-mentioned
      changes in the combination group were more significant. Through the analysis of
      the above experimental results, it is speculated that Astragalus polysaccharides
      may increase the sensitivity of cervical cancer HeLa cells to cisplatin by
      regulating the cell autophagy. Its possible mechanism of action is correlated
      with the up-regulation of autophagy-related proteins beclin1, the promote the
      conversion from LC3I to LC3II, the down-regulation of labeled protein p62, and
      the enhancement of HeLa cell autophagic activity, thereby increasing the
      sensitivity of HeLa cells to cisplatin chemotherapy.

PMID- 29600660
TI  - [Subchondral drilling method combined with gum-bletilla complex to repair
      articular cartilage defects].
AB  - Two types(A model and B model) of articular cartilage defect models were prepared
      by using adult New Zealand white rabbits. A model group was applied by drilling
      without through subchondral bone, whose right joint was repaired by composite
      scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left
      side was blank control. B model group was applied by subchondral drilling method,
      whose right joint was repaired by using composite scaffolds made by gum-bletilla
      and Pluronic F-127 without seed cells, and left side was blank control.
      Autogenous contrast was used in both model types. In addition, another group was
      applied with B model type rabbits, which was repaired with artificial complex
      material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after
      operation, the animals were sacrificed and the samples were collected from
      repaired area for staining with HE, typeIIcollagen immunohistochemical method,
      Alcian blue, and toluidine blue, and then were observed with optical microscope.
      Semi-quantitative scores were graded by referring to Wakitanis histological
      scoring standard to investigate the histomorphology of repaired tissue. Hyaline
      cartilage repairing was achieved in both Group A and Group B, with satisfactory
      results. There were no significant differences on repairing effects for articular
      cartilage defects between composite scaffolds made by seed cell, gum-bletilla and
      Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F
      127 without seed cell. Better repairing effects for articular cartilage defects
      were observed in groups with use of gum-bletilla, indicating that gum-bletilla is
      a vital part in composite scaffolds material.

PMID- 29600661
TI  - [Post-marketing surveillance on Guizhi Fuling Jiaonang based on literature
      review].
AB  - To systemically evaluate the post-marketing safety of Guizhi Fuling Jiaonang.
      Computer retrieval was conducted in Medline, EMbase, the Web of Science, Clinical
      Trials. Gov, the Cochrane Library, CNKI, VIP, WanFang Data and CBM to collect
      relevant information. The papers were then screened according to inclusion and
      exclusion criteria. A total of 234 papers were included in this study, including
      164 randomized controlled trials, 7 quasi-randomized controlled trials, 8 non
      randomized controls, 56 case series, and 1 cohort study. The patients were only
      treated with Guizhi Fuling Jiaonang in 56 studies, and Guizhi Fuling Jiaonang was
      combined with other drugs in 178 studies. The total ADRs/AEs incidence was 1.99%
      in single use of Guizhi Fuling Jiaonang, and 8.21% in combined use, but showing
      no severe adverse reactions. Gastrointestinal system damage was most common in
      mild ADRs. In this study, it was found that the overall safety of Guizhi Fuling
      Jiaonang was acceptable. The direct evidences of the drug's safety case reports
      were systematically analyzed in this study, but the mechanism study on the safety
      of the drug after marketing or the prospective long-term clinical observation
      study was not sufficient, so the further studies on the safety of drug use should
      be conducted in order to provide better guidance for clinical medication.

PMID- 29600662
TI  - [Methodological quality and reporting quality evaluation of randomized controlled
      trials published in China Journal of Chinese Materia Medica].
AB  - To evaluate the methodological quality and reporting quality of randomized
      controlled trials(RCTs) published in China Journal of Chinese Materia Medica, we
      searched CNKI and China Journal of Chinese Materia webpage to collect RCTs since
      the establishment of the magazine. The Cochrane risk of bias assessment tool was
      used to evaluate the methodological quality of RCTs. The CONSORT 2010 list was
      adopted as reporting quality evaluating tool. Finally, 184 RCTs were included and
      evaluated methodologically, of which 97 RCTs were evaluated with reporting
      quality. For the methodological evaluating, 62 trials(33.70%) reported the random
      sequence generation; 9(4.89%) trials reported the allocation concealment;
      25(13.59%) trials adopted the method of blinding; 30(16.30%) trials reported the
      number of patients withdrawing, dropping out and those lost to follow-up;2 trials
      (1.09%) reported trial registration and none of the trial reported the trial
      protocol; only 8(4.35%) trials reported the sample size estimation in details.
      For reporting quality appraising, 3 reporting items of 25 items were evaluated
      with high-quality,including: abstract, participants qualified criteria, and
      statistical methods; 4 reporting items with medium-quality, including purpose,
      intervention, random sequence method, and data collection of sites and locations;
      9 items with low-quality reporting items including title, backgrounds, random
      sequence types, allocation concealment, blindness, recruitment of subjects,
      baseline data, harms, and funding;the rest of items were of extremely low
      quality(the compliance rate of reporting item<10%). On the whole, the
      methodological and reporting quality of RCTs published in the magazine are
      generally low. Further improvement in both methodological and reporting quality
      for RCTs of traditional Chinese medicine are warranted. It is recommended that
      the international standards and procedures for RCT design should be strictly
      followed to conduct high-quality trials. At the same time, in order to improve
      the reporting quality of randomized controlled trials, CONSORT standards should
      be adopted in the preparation of research reports and submissions.

PMID- 29600663
TI  - [Traditional Chinese Medicine data management policy in big data environment].
AB  - As traditional data management model cannot effectively manage the massive data
      in traditional Chinese medicine(TCM) due to the uncertainty of data object
      attributes as well as the diversity and abstraction of data representation, a
      management strategy for TCM data based on big data technology is proposed. Based
      on true characteristics of TCM data, this strategy could solve the problems of
      the uncertainty of data object attributes in TCM information and the non
      uniformity of the data representation by using modeless properties of stored
      objects in big data technology. Hybrid indexing mode was also used to solve the
      conflicts brought by different storage modes in indexing process, with powerful
      capabilities in query processing of massive data through efficient parallel
      MapReduce process. The theoretical analysis provided the management framework and
      its key technology, while its performance was tested on Hadoop by using several
      common traditional Chinese medicines and prescriptions from practical TCM data
      source. Result showed that this strategy can effectively solve the storage
      problem of TCM information, with good performance in query efficiency,
      completeness and robustness.

PMID- 29600664
TI  - [Assessment of soil fertility for cultivation of Chinese herbal medicines].
AB  - The soil fertility has great impacts on the yielding of Chinese medicinal
      materials, as well as the generation of major components. The practices showed
      that soil fertility has been decayed with the growth of cultivation years,which
      is leading to adverse effect on quality and quantity of Chinese medicinal
      materials. However, there was a lack of domestic unified standard for assessment
      of soil fertility of Chinese medicinal material cultivation, which has seriously
      limited the soil management and quality control. In this text, we reviewed the
      progress on research of soil fertility evaluation, built the soil fertility
      evaluation index including soil texture,soil bulk density,soil organic
      matter,soil acidity and alkalinity,soil available nitrogen,soil available
      phosphorus, soil available potassium,soil animals and soil microorganisms. It
      would provide the direction and thought for standard-settin on soil fertility
      evaluation of Chinese medicinal material cultivation.

PMID- 29600665
TI  - [Analysis of eczema animal model based on clinical characteristics].
AB  - The coincidence of the existing eczema animal model and the clinical
      characteristics of eczema, and the application characteristics of eczema animal
      model were analyzed, and the evaluation method and improvement method of
      corresponding eczema animal model was put forward. Based on the clinical
      diagnostic criteria of eczema of traditional Chinese medicine and western
      medicine, the characteristics of current eczema model and the modeling method
      were summarized, and the anastomosis situations between the existing animal model
      and the eczema clinical characteristics were analyzed. At present, the back
      eczema models of mice have been usually used, which reflected the
      pathophysiological characteristics of clinical eczema to a certain degree.
      However, the existing animal models fail to reflect the clinical characteristics
      of traditional Chinese medicine. Future studies focused on establishing animal
      models that better reflect the clinical characteristics of eczema and the index
      system of eczema model.

PMID- 29600666
TI  - [Explore of choice for diagnosis and treatment method for hallux valgus].

PMID- 29600667
TI  - [Application of three-dimensional printing technology to design individual angle
      section on Chevron of hallux valgus osteotomy].
AB  - OBJECTIVE: To explore clinical application of three-dimensional printing
      technology to design individual angle section on Chevron of hallux valgus
      osteotomy. METHODS: From May 2013 to May 2016, 47 patients(66 feet) with mild to
      moderate hallux valgus treated by Chevron osteotomy according to different
      preoperative design were divided into computer osteotomy group(group A) and
      traditional osteotomy group(group B). In group A, there were 25 patients (33
      feet), including 4 males(5 feet) and 21 females(28 feet) with an average age of
      (47.88+/-6.08) years old, average weight IMA was (13.58+/-1.15) degree, AOFAS
      score was 59.00+/-5.86, and treated individual 3D printing technology to design
      operation scheme. While in group B, there were 22 patients (33 feet), including 3
      males (3 feet) and 19 females (28 feet) with an average age of (48.16+/-6.16)
      years old, average weight IMA was(13.51+/-1.14) degree, AOFAS score was 60.67+/
      5.85, and treated with osteotomy according to surgical experience. Operation
      time, blood loss, hospital stays, VAS score at 1 week after operation, wound
      healing and improvement of postoperative weight-bearing intermetatarsal
      angle(IMA) were compared between two groups, AOFAS score system was used to
      evaluate ankle function after surgery. RESULTS: There was no significant
      difference in following-up between group A 12.41+/-2.32 and group B 11.73+/-2.76.
      There was 1 patient in group B were excluded. Others perform good wounds healing
      on the first stage after operation. There were no significant differences in
      operation time, blood loss, hospital stays and VAS score at 1 week after
      operation(P<0.05); IMA in group A was (5.21+/-0.88) degrees , (6.42+/-0.85)
      degrees  in group B, and had significant differences between two groups (t=5.68,
      P<0.05). There was obvious meaning in AOFAS score between group A 88.15+/-5.19
      and group B 82.90+/-5.01(t=4.14, P<0.05). Fourteen feet in group A obtained
      excellent results and 19 feet good, while 5 feet in group B obtained excellent
      results and 27 feet good. CONCLUSIONS: Compared with traditional osteotomy group,
      three-dimensional printing technology to design individual angle section on
      Chevron of hallux valgus osteotomy could better correct IMA, improve
      postoperative foot function, and it is a kind of individualized and digital
      method to design operation.

PMID- 29600668
TI  - [Minimally invasive therapy for hallux valgus with deformity of little toe
      varus].
AB  - OBJECTIVE: To explore clinical effect of minimally corrective osteotomy for the
      treatment of hallux valgus with deformity of little toe varus through small
      incision. METHODS: From January 2013 to June 2016, 168 hallux valgus patients
      with deformity of little toe varus were treated by minimally corrective osteotomy
      through small incision. Among them, 7 males and 161 females were aged from 22 to
      75 years old with an average of(59.3+/-3.5) years old. Preoperative clinical
      manifestation mainly focus on red and swollen of bunion, pain around with
      metatarsal bones, and diagnosed as hallux valgus with deformity of little toe
      varus through small incision. Operative time, postoperative complications, pre
      and post-operative IMA(angle between the first and the second metatarsal bones),
      HVA (hallux valgus angle), LDA(valgus angle of the fifth metatarsal bones),
      MPA(valgus angle of little toe), IM4-5 (angle between the forth and the fifth
      metatarsal bones) and PASA(fixed angle of proximal joint), postoperative AOFAS
      score were used to evaluate foot function. RESULTS: One hundred and sixty-eight
      patients were followed up for 6 to 48 months with an average of (28.6+/-3.2)
      months. All wounds were healed well without infection, sinus tract and other
      complications. Operative time ranged from 16 to 28 min with an average of (18.3+/
      2.1) min. IMA, HVA, LDA, MPA and IM A 4-5 were (10.1+/-2.1) degrees , (32.6+/
      4.2) degrees , (6.9+/-2.3) degrees , (18.5+/-5.2) degrees , (15.1+/-2.9) degrees
      preoperatively, improved to (8.3+/-2.2) degrees , (10.9+/-2.9) degrees , (2.7+/
      0.4) degrees , (6.5+/-1.6) degrees , (8.9+/-1.8) degrees  postoperatively, and
      had significant differences before and after operation. While there was no
      difference in PASA before (9.1+/-2.1) degrees and after operation(8.7+/-1.9)
      degrees . AOFAS score were improved from (31.6+/-3.9) before operation to(83.7+/
      5.2) after operation, but no significant difference(P>0.05). According to AOFAS
      score, 147 patients obtained excellent results, 13 good, 6 moderate and 2 poor.
      CONCLUSIONS: Minimally corrective osteotomy for the treatment of hallux valgus
      with deformity of little toe varus through small incision could obtain satisfied
      clinical effect, and has advantages of small incision, no stitches, beautiful
      appearance, shorter operation time, and rapid recovery. It is worth
      popularization in clinical practise.

PMID- 29600669
TI  - [Clinical effect modified Chevron osteotomy combined with lateral tissue
      loosening in treating mild-moderate hallux valgus through internal signal
      approach].
AB  - OBJECTIVE: To explore clinical effect of modified Chevron osteotomy combined with
      lateral tissue loosening for the treatment of mild-moderate hallux valgus through
      internal signal approach. METHODS: From July 2015 to June 2016, 26 patients with
      mild-moderate hallux valgus treated with modified Chevron osteotomy combined with
      lateral tissue loosening through internal signal approach, including 2 males and
      24 females aged from 45 to 65 years old with an average of(54.6+/-4.8) years
      old;the courses of diseases ranged from 1 to 5 months with an average of (7.5+/
      3.3) months. Hallux valgus angle(HVA), inter metatarsal angle(IMA) were measured
      at 12 months after operation, and AOFAS score was applied to evaluate clinical
      effect before and after operation. RESULTS: All incisions were healed at stage I.
      No incision occurred infection, metatarsal necrosis and recurrence of hallux
      valgus deformity. Two patients occurred skin numbness caused by musculocutaneous
      nerve injury. Twenty-six patients were followed up from 6 to 12 months with an
      average of(9.12+/-2.06) months. HVA, IMA were(30.01+/-3.71) degrees , (14.00+/
      1.50) degrees  before operation and(9.41+/-4.16) degrees , (7.00+/-0.60) degrees 
      after operation, which had significant difference. There was statistical
      significance in AOFAS score before operation 54.77+/-9.59 and after operation
      92.73+/-5.47, and 19 cases obtained excellent results and 7 moderate.
      CONCLUSIONS: Modified Chevron osteotomy combined with full thread headless
      pressure screw fixation and lateral tissue loosening for the treatment of mild
      moderate hallux valgus has advantages of excellent exposure, simple operation,
      stable fixation, rapid recovery. Akin osteotomy with internal capsulorrhaphy were
      used with lateral loosening and could recover soft tissue balance between lateral
      and internal, and could receive satisfied clinical effects.

PMID- 29600670
TI  - [Prospective cases-control study on arthroscopic for the treatment of ischial
      tuberosity cyst].
AB  - OBJECTIVE: To compare technique and clinical effect of arthroscopic and
      conventional sectional therapy for the treatment of ischial tuberosity cyst.
      METHODS: From May 2014 and September 2016, 49 patients with symptomatic ischial
      tuberosity cyst were randomized divided into arthroscopic group and conventional
      section group by envelope method. There were 24 patients in arthroscopic group,
      including 16 males and 8 females aged from 42 to 81years old with an average age
      of (64.1+/-9.3) years old;the courses of disease ranged from 2 to 36 months with
      an average of (17.0+/-9.1) months;treated with removing cyst wall under
      arthroscopic and build artificial lacuna around cyst. There were 25 patients in
      conventional section group, including 11 males and 14 females aged from 47 to 79
      years old with an average of (61.2+/-10.6) years old; the courses of disease
      ranged from 4 to 36 months with an average of (17.5+/-8.5) months;treated with
      cutting off lump with transverse incision. Operative time, blood loss, fluid
      volume, hospital stays and postoperative complication were observed and compared,
      VAS score were applied to evaluate pain degree. RESULTS: Forty-nine patients were
      followed up from 6 to 18 months with an average of (11.3+/-3.3) months. In
      conventional group, 2 patients occurred incision infection, 1 case reoccurred.
      All patients in arthroscopic group were healed at stage I. Operative time, blood
      loss, fluid volume, and hospital stays in arthroscopic group were (54.7+/-7.7)
      min, (20.8+/-3.5) ml, (20.3+/-5.6) ml, (2.8+/-0.6) d respectively and better than
      that of conventional group(71.8+/-8.8) min, (67.3+/-12.0) ml, (103.6+/-20.3) ml,
      (7.8+/-2.9) d. Postoperative VAS score in arthroscopic group on the first day,
      seventh days and first month were 2.6+/-0.7, 0.5+/-0.6, 0.3+/-0.5, and
      significantly lower than that of conventional group 6.0+/-0.7, 3.0+/-1.0, 1.1+/
      1.0 respectively(P<0.05). There were no statistical difference in postoperative
      complications between two groups(P>0.05). CONCLUSIONS: Compared with conventional
      group, arthroscopic for ischial tuberosity cyst has advantages of minimal
      invasive, less blood loss during perioperative period, less pain degree after
      surgery, safety and rapid recovery. But arthroscopic skills are needed for
      surgeons. It should be recommended in clinical practice.

PMID- 29600671
TI  - [Clinical observation of osteotomy and fusion for the treatment of severe rigid
      equinus deformity].
AB  - OBJECTIVE: To explore clinical efficacy of osteotomy and fusion in treating
      severe rigid equinus deformity. METHODS: From April 2010 to October 2015, 13
      patients(16 feet) with severe rigid equinus deformity were treated with osteotomy
      and fusion by hollow screw, including 6 males and 7 females aged from 39 to 62
      years old with an average of(49.6+/-5.3) years old;the courses of diseases ranged
      from 5 to 27 years with an average of (9.0+/-4.8) years. Six patients (9 feet)
      were treated with osteotomy and fusion for three joints, 4 patients(4 feet) were
      treated with osteotomy and fusion for four joints, and 3 patients (3 feet) were
      treated with osteotomy and fusion for tibiotalar and calcaneal-talar joints. All
      patients manifested as foot pain, heel could not touch floor and walking before
      operation. Postoperative complications were observed, AOFAS score were applied to
      evaluate clinical effect. RESULTS: Thirteen patients were followed up from 18 to
      24 months with an average of 20 months. Only one patient occurred local skin
      necrosis after operation and healed by dressing change and anti-infective
      therapy. All feet obtained fracture healing, the time ranged from 12 to 16 weeks
      with an average of 13.2 weeks. AOFAS score were improved from 11.85+/-10.66
      before operation to 81.38+/-3.69 after operation, and had significant
      difference(t=-25.67, P<0.05);15 feet good and 1 foot moderate. CONCLUSIONS:
      Tibiotalar and calcaneal-talar joint fusion, osteotomy and fusion for three and
      four joints could treat severe rigid equinus deformity according to patients'
      individual and could obtain satisfied clinical effects.

PMID- 29600672
TI  - [Case-control study on polymer polylactic acid absorbable medical film for
      preventing acromion adhesion after arthroscopic rotator cuff repair].
AB  - OBJECTIVE: To study effect of shoulder joint function after rotator cuff repair
      of polylactic acid absorbable membrane. METHODS: From September 2015 to December
      2016, 50 patients diagnosed with rotator cuff tear were selected and divided into
      treatment group and control group. There were 25 patients in control group,
      including 12 males and 13 females, with an average age of (48.7+/-3.5) years old,
      who received simple arthroscopic rotator cuff repair. There were 25 patients in
      treatment group, including 11 males and 14 females, with an average age of(49.2+/
      4.1) years old, who performed arthroscopic rotator cuff repair with implanting
      polylactic acid absorbable membraneon shoulder of rotator cuff. Preoperative and
      postoperative VAS score, ASES score and UCLA score were recorded and compared
      between two groups. RESULTS: At 6 months after operation, preoperative VAS score
      in control group was 5.48+/-1.12, and decreased as 1.28+/-0.84 after operation;
      ASES score before operation was 52.24+/-4.64, and improved to 86.92+/-3.20 after
      operation;preoperative UCLA score improved from 14.36+/-1.89 before operation to
      30.72+/-1.28 after operation. In treatment group, VAS score decreased from 5.36+/
      1.32 before operation to 1.40+/-0.71 after operation;preoperative ASES score was
      51.04+/-4.09, and improved to 88.96+/-2.79 after operation; UCLA score improved
      from 15.12+/-1.81 before operation to 32.12+/-1.33 after operation. There was no
      significant difference in VAS score between two groups, and ASES score, UCLA
      score in treatment group was obviously better than control group. CONCLUSIONS:
      Application of polylactic acid absorbable medical membrane could obviously
      improve shoulder function, and effectively prevent acromion adhesion after
      arthroscopic rotator cuff repair.

PMID- 29600673
TI  - [Clinical efficacy analysis of transverse tibial bone transport combined with
      vacuum drainage for the treatment of diabetic foot ulcer].
AB  - OBJECTIVE: To investigate clinical effect of transverse tibial bone transport
      micro vessels regeneration technology combined with vacuum drainage in treating
      diabetic foot ulcer. METHODS: From November 2015 and December 2016, clinical data
      of 19 diabetic foot ulcer patients treated with transverse tibial bone transport
      micro vessels regeneration technology combined with vacuum drainage were
      retrospective analyzed, including 15 males and 4 females aged from 42 to 82 years
      old with an average of (64.57+/-7.14) years old;the courses of diabetic ranged
      was (14.62+/-6.19) years;12 cases on the left side and 7 cases on the right
      side;the area of ulcer ranged from 2 cm*3 cm to 8 cm*6 cm. All patients were
      stage D according to Texas classification, 3 cases were grade 2, 10 cases were
      grade 3 and 6 cases were grade 4. Ankle-brachial index and Michigan Neuropathy
      Screening Instrument (MNSI) were used to evaluate recovery of peripheral vessel
      and nerve before and after operation, the result of angiography and vascular
      ultrasound were also compared after operation. RESULTS: Seventeen of 19 patients
      were followed up from 3 to 13 months with an average of 6.9 months. Seventeen
      patients' surface wound were healed. Ankle-brachial index was increased from
      (0.51+/-0.20) before operation to (0.93+/-0.18) at 3 months after operation, and
      had significant difference(t=13.63, P=0.000);MNSI was increased from (4.06+/
      1.36) before operation to(5.76+/-1.44) at 3 months after operation, and
      differences were statistically significant (t=7.31, P=0.000). Postoperative
      angiography and vascular ultrasound showed satisfied regeneration of micro-vessel
      and affected foot achieved normal movement and daily life. CONCLUSIONS:
      Transverse tibial bone transport micro vessels regeneration technology could
      reconstruct micro-vessel under lower affected limb, promote recovery of
      peripheral vessel and nerve, while with vacuum drainage could promote wound
      healing, has advantages of simple operation, obvious clinical effect, and high
      success rate of limb-salvage, and is one of ideal treatment for diabetic foot
      ulcer.

PMID- 29600674
TI  - [Clinical efficacy of locked fibular nail for the treatment of lateral malleolus
      fractures in elderly patients with diabetes].
AB  - OBJECTIVE: To explore clinical outcome of locked fibular nail in treating lateral
      malleolus fractures in elderly patients with diabetes. METHODS: From July 2012 to
      July 2014, clinical data of 22 diabetic patients with lateral malleolus fractures
      were respectively analyzed, including 15 females and 7 males, aged from 62 to 84
      years old with an average of (69.3+/-13.7) years old. According to Danis-Weber
      classification, 2 cases were type A, 13 cases were type B, 5 cases were type C,
      and 2 cases were other type. All patients were reduced and fixed with Acumed
      locked fibular nail through a minimally invasive approach. Complication and
      fracture healing was recorded after operation. Clinical function was evaluated
      according to AOFAS. RESULTS: All patients were followed up from 12 to 24 months
      with an average of (17.3+/-5.9) months. All incisions were healed at stage I. No
      wound complication, neurovascular or tendon injuries occurred. No fixation loss
      or discomfort of nail was reported. All patients achieved primary bone union, and
      healing time ranged from 8 to 14 weeks with an average of (10.3+/-3.9) weeks.
      AOFAS score was 87.4+/-5.2 at 1 year after operation 9 cases got excellent
      results and 12 cases good. CONCLUSIONS: For elderly diabetic patients with
      lateral malleolus fractures, locked fibular nail has advantages of effective and
      stable fixation, high rate of bone healing, short healing time, less
      complication, and could obtain satisfied clinical effect.

PMID- 29600675
TI  - [Establish mouse osteoblast -osteoclast cell co-culture system in a Transwell
      chamber].
AB  - OBJECTIVE: To establish osteoblast-osteoclast cell co-culture system in a
      Transwell chamber, and detect cell viability of osteoblasts and osteoclasts in
      system. METHODS: Osteoblast MC3T3-E1 and mouse monocytes RAW264.7 were cultivated
      in vitro. RANKL-induced mouse RAW264.7 monocytes differentiated into mature
      osteoclasts, osteoblast-osteoclast cell co-culture system was established in
      Transwell chamber. Cell activity of osteoblasts and osteoclasts were detected by
      CCK-8 experimenting, Alizarin Red staining, TRAP staining. The expression of OPG,
      ALP, RANKL, TGF-b1 gene and RANKL protein in osteoblast MC3T3-E1 were detected by
      PCR, Western-Blot methods. Also, the expression of RANK, NF-kappaB in gene and
      protein level in osteoclast were measured through the same method respectively.
      RESULTS: The co-culture system of Mouse MC3T3-E1 cells and RAW264.7 cell were
      established in Transwell chamber. Co-culture system affected cell division
      activities of osteoblasts and osteoclasts. Differentiation of osteoblasts were
      increased, while differentiation of osteoclast division were slight decreased
      under microscope observation. OPG (0.65+/-0.08) and ALP (0.16+/-0.01) gene
      expression of co-culture system were less than single culture OPG(1.00+/-0.08)
      and ALP (1.01+/-0.16); TGF-b1(4.42+/-0.21) and RANKL(4.12+/-1.04) of osteoblasts
      in co-culture system were higher than TGF-b1(1.00+/-0.10) and RANKL(1.00+/-0.09)
      under single culture. However, gene expression of RANK(0.63+/-0.06) and NF
      kappaB(0.64+/-0.08) in co-culture system were decreased than RANK(1.00+/-0.08)
      and NF-kappaB(1.00+/-0.09), in single culture, and had significant differences.
      Similarly, protein expression of OPG(0.43+/-0.05) and NF-kappaB(0.59+/-0.05) of
      co-culture system were less than OPG(0.84+/-0.06) and NF-kappaB(1.13+/-0.03) of
      single culture. While RANKL protein expression (0.54+/-0.03)of co-culture system
      was more than single culture RANKL(0.31+/-0.03), and had statistically
      differences, which was in agreement of the trend of gene expression change.
      CONCLUSIONS: Co-culture system of mouse MC3T3-E1 cells and RAW264.7 cell was
      viable in Transwell chamber, and the activity of osteoblasts is higher than
      osteoclasts in co-culture system.

PMID- 29600676
TI  - [Osteopractic total flavone promoting rat extra-articular tendon-bone healing
      through mTOR pathway].
AB  - OBJECTIVE: To explore function and related molecular mechanism of osteopractic
      total flavone (OTF) on tendon healing in rats. METHODS: Ten male rats aged for 8
      weeks were collected and weighted from 180 to 220 g. Tendon stem cells were
      cultivated, the third tendon stem cells were used for experiment. OTP treated
      with 0, 0.1, 1, 10 ng/ml were added into tendon stem cells, and expression change
      of ALP, Runx2, OCN, VEGF, P-S6, P-4E/BP1 were detected after 14 days. Forty male
      rats aged for 8 weeks (weighted 180 to 220 g) were established extra-articular
      tendon-bone transplanting healing model, and divided into experimental group and
      control group. Experimental group were treated with OTF(100 mg.kg-1.d-1), while
      control group was treated by normal saline with the same volume. Tendon-bone
      healing degree were detected by biomechanical testing at 3 and 6 weeks after
      surgery, histological detection were applied to detect tendon-bone healing and
      number of new vessles. RESULTS: After treated by OTP, ALP staining and active
      index detection showed there were statistical differences among 0, 0.1, 1, 10
      ng/ml group. After 14 days' cultivation, western blotting results showed mTOR
      downstream marker protein P-S6 protein expression were gradually increased with
      increase of density of OTP, expression of P-4E/BP1 was reduced, while expression
      of Runx2, OCN, VEGF were increased. Biological detection results showed that
      there was no significant difference in mechanical strength between experimental
      group(0.78+/-0.05) N/mm and control group (0.51+/-0.02) N/mm at 3 weeks after
      surgery, while mechanical strength in experimental group (1.36+/-0.09) N/mm was
      higher than control group (1.01+/-0.08) N/mm at 6 weeks after surgery.
      Histological results showed maturity of tendon-bone surface cell were higher at 3
      and 6 weeks in experimental group, sharpey fiber growth more density,
      calcification extent of mesenchyme was high, and new bone, vessels were
      increased. CONCLUSIONS: OTF could promote osteogenic differentiation of tendon
      stem cells through mTOR signaling in vitro, and stimulate tendon-bone healing in
      bone tunnel and enhance connection quality between tendon and bone.

PMID- 29600677
TI  - [Manual reduction and traction fixation for the treatment of metacarpal neck
      fractures under ultrasound-guided].
AB  - OBJECTIVE: To study clinical efficacy of manual reduction and traction fixation
      for the treatment of metacarpal neck fracture under ultrasound-guided. METHODS:
      From April 2013 to August 2016, 30 patients with metacarpal neck fractures were
      treated with manual reduction and traction fixation under ultrasound-guided,
      including 26 males and 4 females aged from 14 to 56 years old with an average of
      (25.6+/-1.6) years old, the courses of diseases ranged from 7 h to 5 d with an
      average of (2.7+/-0.6) d. Twenty patients were the fifth metacarpal neck
      fracture, 7 patients were the 4th and 5th metacarpal neck fractures, 3 patients
      were the second metacarpal neck fracture. Fracture healing, angle of bilateral
      head shaft angle and active range of metacarpophalangeal joints was measured, and
      DASH score was applied to evaluate function. RESULTS: Twenty-seven patients were
      followed up from 6 to 11 months with an average of(7.2+/-0.8) months. Fracture
      were healed from 5 to 8 weeks with an average of (5.6+/-0.4) weeks. The affected
      shaft angle was (15.1+/-1.8) degrees , and health head shaft angle was (13.5+/
      2.8) degrees , while there was no significant difference (t=1.54, P>0.05). The
      affected range motion of metacarpophalangealjoint was(86.3+/-2.6) degrees ,
      health active range motion of metacarpophalangeal joint was(91.8+/-1.6) degrees ,
      and no significant difference between both side (t=1.16, P>0.05). DASH score was
      4.3+/-1.5 at 7 months after operation. CONCLUSIONS: Manual reduction and traction
      fixation for the treatment of metacarpal neck fracture under ultrasound-guided
      could dynamic observe fracture position in time, high patients' acceptability and
      is a feasible method for the treatment of metacarpal neck fracture.

PMID- 29600678
TI  - [Mid-term follow-up and clinical efficacy of total knee arthroplasty for
      osteoarthritis patients with Parkinson's disease].
AB  - OBJECTIVE: To investigate clinical efficacy and experience of total knee
      arthroplasty in treating knee osteoarthritis patients with Parkinson's disease.
      METHODS: From January 2011 to January 2014, 19 knee osteoarthritis patients with
      Parkinson's disease treated with total knee arthroplasty were collected. Among
      them, including 9 males and 10 females aged from 61 to 83 years old with an
      average of 71.3 years old. Radiology results were checked before and after
      operation. VAS score and KSS score were applied to evaluate clinical effects.
      Patients were classified according to HoehnYahr grade, 3 cases in grade 1, 4
      cases in grade 1.5, 2 cases in grade 2, 4 cases in grade 2.5, 2 cases in grade 3
      and 1 case in grade 4. RESULTS: Nineteen patients were followed up from 3 to 7
      years with an average of 4.3 years. The pain of patients was significantly
      reduced or disappeared. All incisions were healed at stage I. At the latest
      follow-up, 3 patients had knee pain, and mild pain in 1 patient, moderate in 1
      patient without severe pain. VAS score was reduced from preoperative 8.4+/-1.3 to
      the latest follow-up 3.1+/-1.2, the difference was statistically significant
      (P<0.05). KSS score improved from 43.6+/-7.3 before operation to 91.8+/-10.6
      after operation. The condition of Parkinson's were controlled by medicine. No
      loosening and subsidence of prosthesis by X-ray examination. CONCLUSIONS: Total
      knee arthroplasty is a safe and effective method for the treatment of Parkinson's
      disease and has satisfactory mid-term clinical effect.

PMID- 29600679
TI  - [Diagnostic value of MRI for posterior root tear of medial and lateral meniscus].
AB  - OBJECTIVE: To explore diagnostic value of MRI on posterior root tear of medial
      and lateral meniscus. METHODS: From January 2012 to January 2016, clinical data
      of 43 patients with meniscal posterior root tear confirmed by arthroscopy were
      retrospective analyzed, including 25 males and 18 females, aged from 27 to 69
      years old with an average age of(42.5+/-8.3)years old;27 cases on the right side
      and 16 cases on the left side. MRI examinations of 43 patients with tear of
      posterior meniscus root confirmed by knee arthroscopies were retrospectively
      reviewed. MRI images were double-blinded, independently, retrospectively scored
      by two imaging physicians. Sensitivity, specificity and accuracy of MRI diagnosis
      of lateral and medial meniscus posterior root tear were calculated, and knee
      ligament injury and meniscal dislocation were calculated. RESULTS: Forty-three of
      143 patients were diagnosed with meniscus posterior root tears by arthroscopy,
      including 19 patients with lateral tears and 24 patients with medial tears. The
      sensitivity, specificity and accuracy in diagnosis of posterior medial meniscus
      root tears for doctor A were 91.67%, 86.6% and 83.9% respectively, and for doctor
      B were 87.5%, 87.4% and 87.4%, 19 patients with medial meniscal protrusion and 2
      patients with anterior cruciate ligament tear. The sensitivity, specificity and
      accuracy in diagnosis of posterior lateral meniscus root tears for doctor A were
      73.7%, 79.9% and 79% respectively, and for doctor B were 78.9%, 82.3% and 82.5%,
      4 patients with lateral meniscus herniation and 16 patients with cruciate
      ligament tear. Kappa statistics for posterior medial meniscus root tears and
      posterior lateral meniscus root tears were 0.84 and 0.72. CONCLUSIONS: MRI could
      effectively demonstrate imaging features of medial and lateral meniscal root tear
      and its accompanying signs. It could provide the basis for preoperative diagnosis
      of clinicians, and be worthy to be popularized.

PMID- 29600680
TI  - [Meta plate and cannulated screw fixation for treatment of type Letenneur III
      lateral Hoffa fracture through posterolateral approach].
AB  - OBJECTIVE: To explore clinical effect of meta plate with cannulated screw
      fixation in treating Letenneur III lateral Hoffa fracture through posterolateral
      approach. METHODS: From June 2012 to June 2016, 12 patients with Letenneur III
      lateral Hoffa fracture were treated with meta plate and cannulated screw fixation
      through posterolateral approach, including 8 males and 4 females;aged from 22 to
      66 years with an average of 42 years old;and 5 cases on left side, 7 cases on
      right side. Preoperative and postoperative X-ray and CT were taken before and
      after operation to assess location of fracture and fracture healing. Letenneur
      scoring standard was used to evaluate clinical effects. All patients were treated
      with meta plate combined with cannulated screws. RESULTS: All incisions healed at
      stage I. The fractures were healed from 11 to 32 weeks with an average of 17.2
      weeks. No internal fixation loosening, displacement and necrosis of femoral
      condyle and deep vein thrombosis of lower extremity occurred. All patients were
      followed up from 8 to 24 months with an average of 12.8 months. At the latest
      follow-up, 7 cases got excellent results, 4 good and 1 moderate according to
      Letenneur scoring standard. CONCLUSIONS: Posterlateral approach is easy to
      expose, meta plate fixation with cannulated screws has advantages of strong
      internal fixation, high fracture healing rate, early knee joint function exercise
      and good recovery of joint function.

PMID- 29600681
TI  - [Imaging findings of bone infarction in children with systemic lupus
      erythematosus].
AB  - OBJECTIVE: To investigate diagnostic value of MRI, X ray and CT for bone
      infarction in children with systemic lupus erythematosus. METHODS: Eleven
      systemic lupus erythematosus children with bone infarction were retrospectively
      analyzed from January 2015 to January 2017 , and tested by MRI, X-ray and CT.
      Among them, including 1 male and 10 females aged from 6 to 16 years old with an
      average of 13 years old. All patients were detected by MRI, 9 patients were
      detected by X-ray and 3 patients were detected by CT, imaging findings were
      analyzed. RESULTS: The location of bone infarction involved 60 sits, 30 sites
      located on metaphyseal-diaphyseal region, 8 located on patella, 21 located on
      epiphysis, and 1 located on talus. Focus of 11 patients were detected by MRI, the
      main manifestation showed geographic change, long T1 and T2 signal could seen
      around focus, and showed double ring sign and three ring sign; 5 of 9 patients by
      X-ray examination detected focus;2 of 3 patients by CT examination detected
      focus. No abnormity seen at early stage by X-ray and CT examination, and low
      density focus around harden edge at chronic stage. CONCLUSIONS: MRI could display
      bone fracture at early stage, X-ray and CT could only display lesion at chronic
      stage, MRI is the most effective method in diagnosing bone infarction.

PMID- 29600682
TI  - [A case report of tranexamic acid associated epilepsy in spine surgery].

PMID- 29600683
TI  - [Spinal cord compression caused by tophus in epidural lipoma:a case report].

PMID- 29600684
TI  - [Current advances on surgical treatment for knee articular cartilage injuries].
AB  - Chondral injuries are short of self-healing ability and need to surgical repair
      after articular cartilage injury. Conventional treatment includes debridement and
      drainage under arthroscope, micro-fracture, osteochondral autograft
      transplantation (OATS), mosaiplasty and osteochondral allografts (OCA),
      autologous chondrocyte implantation (ACI). Debridement and drainage could remove
      pain factor, and has advantages of simple operation, wide clinical application
      and early clinical effect. Micro-fracture and osteochondral autograft
      transplantation is suitable for small area of cartilage repair, while the further
      effect showed that fibrous cartilage permeated by drill could decrease
      postoperative clinical effect. Osteochondral autograft transplantation has better
      advantages for reconstruction complete of wear-bearing joint. Autologous
      chondrocyte implantation and allogeneic cartilage transplantation are suitable
      for large area of cartilage defect, postoperative survival of allogeneic
      cartilage transplantation is effected by local rejection reaction and decrease
      further clinical effect. Cartilage tissue engineering technology could improve
      repair quality of autologous chondrocyte implantation, and make repair tissue
      close to transparent cartilage, but has limit to combined subchondral bone plate,
      reactive bone edema, bone loss and bad axis of lower limb. New technology is
      applied to cartilage injury, and has advantages of less trauma, simple operation,
      rapid recover, good clinical effect and less cost;and could be main method for
      treat cartilage injury with surgical repair technology. How to improve repair
      quality with compression resistance and abrasive resistance are expected to be
      solved.

PMID- 29600685
TI  - [Long non-coding RNA for metabolism of bone tissue].
AB  - The mechanism of metabolism of bone and cartilage are one of focus of orthopedic
      knowledge, and its clinical and basic study plays an important role in preventing
      and treating osteoporosis, degeneration of bone and joint, bone tumor. At
      present, the mechanism of metabolism of bone and cartilage studied from protein,
      signal pathway to mRNA transcription factor regulation. As a new regulatory
      factor for non-coding proteins, long non-coding RNA(LncRNA) participates in
      physiological and pathological process. In recent years, a large number of
      researche showed that LncRNA plays an important role in metabolism of bone and
      cartilage, and proved LncRNA participates in development and conversion of bone
      metabolism. With the exposure of function chennel and target of LncRNA, the key
      role of LncRNA in bone metabolism were proved constantly. The paper concluded
      biological characteristics of LncRNA, function and target spot of LncRNA in bone
      and cratilage metabolism, and in further state gene regulatory mechanism of bone
      and cartilage metabolism, explore diagnosis and treatment, provide new thought
      and treatment target for bone metabolism.

PMID- 29600686
TI  - [Treatment progress on giant cell tumors of bone].
AB  - Giant cell tumors(GCT) of bone is benign bone tumors with aggressive and
      osteolytic activity. As traditional treatment of GCT, removal of bone graft is
      disease with high local recurrence rate, and could reduce local recurrence by
      auxiliary means. Different surgical methods such as prosthesis replacement, wide
      resection and En-bloc resection could be selected for different parts of giant
      cell tumor of bone, based on the lesion location, size, extent of invasion,
      recurrence rate. For patients with special region of GCT of bone with removed
      incompletely and high surgical risk expected, arterial embolism could be
      performed. The application of bisphosphonates and denosumab are mainly used in
      treating recurrent, refractory, special parts, metastatic giant cell tumor of
      bone will bring new hope of treatment for giant cell tumor of bone, due to lower
      the recurrence rate. Chemotherapy is mainly used in the treatment of metastasis
      and malignant bone tumor. Radiotherapy for recurrent or unresectable bone giant
      cell tumor can control tumor progression, but there is the possibility of
      malignancy. While long-term follow-up studies and long-term results of
      applications of bisphosphonates and denosumab are lacking, new methods and
      development of new drugs are still be needed to treat patients with giant cell
      tumor of bone and also bring about more hope.

PMID- 29600688
TI  - Early robot-assisted gait retraining in non-ambulatory patients with stroke: a
      single blind randomized controlled trial.
AB  - BACKGROUND: Restoration of walking function is a primary concern of
      neurorehabilitation with respect to the aspired social and vocational
      reintegration. To date, the best practice for improving gait early after stroke
      is still object of debate. On one hand, repetitive task-specific approaches with
      higher intensities of walking have been observed to result in greater
      improvements of gait after stroke. Conversely there is some evidence that
      conventional gait training would be more effective for facilitating walking
      ability after stroke. AIM: To compare the effects of an early treatment protocol
      of add-on robot-assisted gait training with add-on conventional overground
      physiotherapy for improving locomotion in non-ambulatory adult stroke patients.
      DESIGN: Single-blind randomized controlled trial. SETTING: Neurorehabilitation
      hospital. POPULATION: Seventy-four subacute patients with first-ever ischemic
      stroke. METHODS: The patients were randomized into two groups. The training
      program consisted of forty, 2-hour sessions (including 45 minutes basic training,
      45 minutes add-on training plus rest periods), five days a week, for eight
      consecutive weeks. Patients allocated to the add-on robot-assisted gait training
      were treated by means of the Lokomat. Patients allocated to the add-on
      conventional overground gait training aimed at improving postural control during
      gait, body weight transfer, stability during the stance phase, free swing phase,
      adequate heel contact and gait pattern. Primary outcome was the modified Emory
      Functional Ambulation Profile. Secondary outcomes were the Rivermead Motor Index,
      the Mobility Milestones and the Hochzirl Walking Aids Profile. RESULTS: No
      significant difference was observed between groups with regards to age (P=0.661),
      time from stroke onset (P=0.413) and the primary outcome (P=0.854) at baseline
      evaluation. As to the primary outcome, no significant differences were found
      between groups at the end of the study. As During the 8-week training, within
      group comparisons showed significant improvements of mean modified Emory
      Functional Ambulation Profile in both groups (P<0.001). CONCLUSIONS: Our results
      support the hypothesis that an early treatment protocol of robot-assisted gait
      retraining is not superior to add-on conventional gait training intervention for
      improving locomotion in non- ambulatory stroke patients. CLINICAL REHABILITATION
      IMPACT: This study might help to better understand the role of robot-assisted
      gait training in early phase stroke rehabilitation.

PMID- 29600687
TI  - Psychometric properties of the Cumulated Ambulation Score: a systematic review.
AB  - INTRODUCTION: In the geriatric population, independent mobility is a key factor
      in determining readiness for discharge following acute hospitalization. The
      Cumulated Ambulation Score (CAS) is a potentially valuable score that allows day
      to-day measurements of basic mobility. The CAS was developed and validated in
      older patients with hip fracture as an early postoperative predictor of short
      term outcome, but it is also used to assess geriatric in-patients with acute
      medical illness. Despite the fast-accumulating literature on the CAS, to date no
      systematic review synthesizing its psychometric properties has been published.
      Therefore, we aimed to provide a comprehensive review of the psychometric
      properties of the CAS, summarizing the present evidence on this measure as a
      basis for further research to investigate its applicability across a wider range
      of functional abilities and care settings. EVIDENCE ACQUISITION: A literature
      search was conducted on research articles published between 2006 and June 2016 in
      journals indexed by MEDLINE and Scopus databases using as a search item
      "Cumulated Ambulation Score"[All Fields], and selecting studies that presented a
      psychometric analysis of the scale. Of 49 studies identified, 17 examined the
      psychometric properties of the CAS. EVIDENCE SYNTHESIS: Most papers dealt with
      patients after hip fracture surgery, and only 4 studies assessed the CAS
      psychometric characteristics also in geriatric in-patients with acute medical
      illness. Two versions of CAS (CAS1 and the more detailed CAS2 version) and two
      different methods to calculate the total score (1-day and 3-day CAS) were used in
      the selected papers. Most of the papers assessed reliability and validity, using
      different statistics, and only one showed evidence of sensitivity to change of
      the score. CONCLUSIONS: This systematic review shows international interest of
      researchers in the CAS, despite the short time frame since its first publication
      in 2006. The results support the reliability, validity, and sensitivity to change
      of the tool. Since different versions of CAS are available and two scores are
      commonly used, we suggest that clinicians and researchers in the future choose
      the more detailed CAS2 version, already used by the large majority of studies,
      and report whether they used the 1- or 3-day score.

PMID- 29600689
TI  - Cancer rehabilitation: closing the gap in low- and middle-income countries.

PMID- 29600690
TI  - Occurrence of Lyme disease infection in a non endemic area in Northern Italy.
AB  - BACKGROUND: In Italy, the incidence of human tick borne disease has increased
      over the last decades. Since 2015 a multidisciplinary group has been established
      in Sacco Hospital for the management of the patients affected by Lyme Disease
      (LD). A retrospective evaluation (2015-2017) was performed for LD in non-endemic
      areas. METHODS: Retrospective analysis of all 1000 samples for 800 patients
      screened for LD antibodies at the Sacco Hospital in 3 years (2015-2017). Revision
      of clinical et epidemiological patients data available and correlation with the
      serological results. RESULTS: Among the 800 patients screened only 134 of them
      were diagnosed with borreliosis: 37 cases during 2015, 31 during 2016 and 66
      during 2017. Localized Lyme disease was diagnosed of 134 cases (69%): in most of
      them (N=63) erythema migrans (EM) has been documented; in 37 out of 100 it was
      not possible to detect it. In only three cases, patients complained of different
      clinicali symptoms such as headache, arm and facial pain respectively. 23 out of
      144 cases (16%) showed a persistence of serological positivity and symptoms with
      osteomuscular involvement and fatigue, despite the therapy (Late Lyme disease).
      In that same study 11 out of 144 patients (7%) received a diagnosis of
      neuroborreliosis. CONCLUSIONS: Our data reported an high percentage of Lyme
      Disease infection (19%) in non endemic area. The definition of a
      multidisciplinary working group and a clinical care pathway allowed a better
      clinical management of Lyme disease cases treated in Sacco Hospital, Milan.

PMID- 29600691
TI  - A giant annular rash in a tuscanian woodman: the many faces of erythema chronicum
      migrans.

PMID- 29600692
TI  - The window of opportunities for targeted therapy in BRAFwt/NRASwt/KITwt melanoma:
      biology and clinical implications of fusion proteins and other mutations.
AB  - Treatment options in advanced melanoma have been subject to a major change over
      the last years. The discovery of the oncogenic point mutation BRAFV600E and
      subsequently developed BRAF inhibitors had a major impact on patient's survival.
      Further important mutations have been found in the NRAS gene, although not yet
      druggable, and others involve c-kit in acral and mucosal melanoma. Imatinib was
      shown to achieve high response rates in c-kit mutated melanoma. Despite good
      response rates in these targeted therapies and introduction of immunotherapy,
      there are still patients left, who develop resistance upon therapy or patients
      without the option of targeted therapy. Therefore it is necessary to identify
      further therapeutic options for this subset of patients. Several new mutations
      have been described so far that might be suitable for targeted therapy or useful
      as clinical biomarkers. Alterations in various receptor tyrosine kinases lead to
      constitutively activated downstream signaling and might be responsible for non
      response to common therapies. In contrast, tyrosine kinase inhibitors such as
      sunitinib or nilotinib could be suitable for patients harboring those
      alterations. Additionally, chromosomal rearrangements have been described in many
      different cancer types, resulting in oncogenic fusion proteins that involve BRAF,
      ROS1, NTRK, ALK and others. These are an emerging therapeutic field, especially
      in spitzoid melanomas. Further mutations have been detected in the neurofibromin
      1 and RAC1 gene, although the clinical relevance is still not fully revealed.
      Within this review we will summarize the current evidence and focus on possible
      further upcoming targets and therapeutic opportunities in BRAFwt/NRASwt/KITwt
      melanoma.

PMID- 29600693
TI  - Photodynamic therapy for aesthetic-cosmetic indications.
AB  - Photodynamic therapy (PDT) is a well-established, non-invasive treatment for a
      variety of dermatologic disorders, including actinic keratosis. Furthermore, PDT
      results in marked improvements in the signs of skin aging, although currently
      there are no standardized guidelines for PDT in skin rejuvenation. Two types of
      PDT are available: conventional-PDT (c-PDT) and the newly introduced daylight-PDT
      (DL-PDT). Both require a topical photosensitizer, a light source and oxygen, and
      both are comparable regarding safety and efficacy for treatment of photo-induced
      skin aging. Treatment is particularly effective for improvement of fine wrinkles,
      skin roughness, actinic elastosis and mottled hyperpigmentation. The most widely
      studied topical sensitizers used in PDT are 5-aminolevulinic acid (ALA) and
      methyl aminolevulinate (MAL). A range of pre-treatment procedures help improve
      skin absorption of the photosensitizer and lead to significantly improved
      efficacy. A variety of activating light sources can be used for c-PDT, while DL
      PDT uses natural daylight, making it easier to treat larger areas of photodamaged
      skin. A major limitation of c-PDT is significant treatment-related pain, but DL
      PDT has proved to be an almost pain-free procedure. Treatment duration is based
      on individual patient need but most patients receive 2 to 3 treatment cycles,
      with results fully evident 3-6 months post-treatment. PDT for aesthetic-cosmetic
      treatments has established its value in modern procedural dermatology as mono- or
      combination therapy. A major, unique advantage of PDT is that it is a non
      invasive treatment that effectively rejuvenates photodamaged skin, while
      successfully treating a range of dermatologic conditions, including prevention
      and therapy of pre-cancerous actinic keratosis.

PMID- 29600694
TI  - Juvenile myelomonocytic leukemia in a patient with neurofibromatosis type 1 and
      xanthogranulomas.

PMID- 29600695
TI  - May syphilis protect against human papillomavirus infection? An example of
      heterologous immunity.

PMID- 29600696
TI  - Helicobacter pylori in metabolic related diseases.
AB  - Helicobacter pylori is one of the most common gastrointestinal infection
      affecting humans worldwide. Hp colonizes the stomach with preferential trophism
      for the antrum. Hp infection is associated with the development of a chronic
      gastritis and subsequently with several gastric diseases such as peptic disease,
      gastric carcinoma and MALT lymphoma. Moreover, Helicobacter pylori infection has
      also been reported in literature to be associated with many other extra-gastric
      conditions including sideropenic anemia, thrombocytopenia, neurological, liver
      and cardiovascular diseases. For some conditions the association is supported by
      solid literature data and also by the identification of the possible
      physiopathogenetic mechanism involved. In other cases, the link is only reported
      by association studies often with conflicting results. In this context, diabetes
      mellitus, cardiovascular disorders and liver steatosis have all been reported to
      be associated with Helicobacter pylori infection. Interestingly, these conditions
      share many characteristics and they often overlap as they represent the
      expression of the so called metabolic syndrome. Aim of the review was to
      summarize the available data regarding the association between Helicobacter
      Pylori infection and diabetes mellitus, cardiovascular disorders and liver
      steatosis.

PMID- 29600697
TI  - Pharmacological considerations and step-by-step proposal for the treatment of
      Helicobacter pylori infection in the year 2018.
AB  - Over the past 30 years, multidrug regimens consisting of a proton pump inhibitor
      (PPI) and two or three antibiotics have been used in treating Helicobacter pylori
      (H. pylori) infection. In clinical practice, the optimal regimen to cure H.
      pylori infection should be decided regionally. Considering the first treatment,
      the Maastricht V/Florence Consensus Report and the American College of
      Gastroenterology Clinical Management Guideline highlight that in countries with
      low clarithromycin resistance rates (<15%), an empiric clarithromycin-based
      regimen can be used. In countries with high clarithromycin resistance rates or,
      in the American Guideline, with a previous exposure to clarithromycin, a bismuth
      containing quadruple therapy (with metronidazole and tetracycline) is the first
      choice. In case of persistent infection, after a previous clarithromycin
      containing regimen, this drug should be avoided in second line therapy. Options
      after initial eradication failure include tailored therapy (choosing antibiotic
      combinations based on antibiotic susceptibility testing), empiric bismuth
      containing quadruple therapy or triple levofloxacin-based therapy. Encouraging
      data are reported, both for the first-line and for rescue treatments, with the
      use of a formulation of bismuth subcitrate potassium, metronidazole, and
      tetracycline contained in a single capsule, together with a PPI. Rifabutin- and
      furazolidone-based regimens should also be considered in rescue regimens.
      Vonoprazan, a new type of potassium-competitive acid blocker that produces more
      potent acid inhibition than PPIs, provides improved H. pylori eradication rates
      in combination with antibiotics. In this review, the authors provide an overview
      on the current knowledge on the treatment of H. pylori infection, with focus on
      therapeutic challenges in this field.

PMID- 29600698
TI  - The role of microbiota in autism spectrum disorders.
AB  - Autism spectrum disorder (ASD) defines a set of neurodevelopmental disorders
      characterized by persistent deficits in social communication and interaction,
      along with repetitive patterns of behavior. Symptoms generally appear in the
      early developmental period and cause significant impairment in individual and
      social functioning. In recent years the increased prevalence of ASD, along with
      the evidence of a significant link between autism and gastrointestinal (GI)
      disturbances, raised a special interest in exploring the reciprocal influences
      between gut and brain. Investigators highlighted the existence of a so-called
      "gut-brain axis," empowering the hypothesis that GI abnormalities could trigger
      neuropsychiatric symptoms in ASD. Intestinal microbiota is thought to play a
      pivotal role in gut and systemic homeostasis, in central nervous system
      development, as well as in behavioral modulation and recurrent microbial
      imbalances have been shown in gut microbiota of autistic people. In this review
      we analyze current knowledge about intestinal microbiota and the relevance and
      role of dysbiosis in ASD. The most accredited theories about gut-brain
      interaction will be reviewed, along with current scientific evidence supporting
      the relationship between microbial imbalances and impairment of neurodevelopment.
      Finally, we will focus on the results of different therapeutic approaches in this
      context: administration of pre- and probiotics, antibiotics, fecal microbiota
      transplantation and special diets and dietary supplements.

PMID- 29600699
TI  - Cyanopyrimidine-Carbazole Hybrid Host Materials for High-Efficiency and Low
      Efficiency Roll-Off TADF OLEDs.
AB  - Two isomeric host materials (Sy and Asy) comprising carbazole (donor) and CN
      substituted pyrimidine (acceptor) were synthesized, characterized, and utilized
      as host materials for green and blue thermally activated delayed fluorescence
      (TADF) organic light emitting diodes (OLEDs). Both molecules have high triplet
      energy and small energy difference between singlet and triplet states, leading to
      feasible TADF. The different linking topologies of carbazole and CN groups on the
      pyrimidine core provide distinct photophysical properties and molecular packing
      manners, which further influence the efficiency as they served as hosts in TADF
      OLEDs. As compared to Asy-based cases, the Sy-hosted TADF OLED device gave higher
      maximum external quantum efficiencies (EQE) of 24.0% (vs 22.5%) for green (4CzIPN
      as a dopant) and 20.4% (vs 15.0%) for blue (2CzTPN as a dopant) and low
      efficiency roll-off. The high horizontal dipole ratio (Theta ~ 88%) for both
      emitters dispersed in Sy and Asy hosts accounts for the high device efficiency. A
      clear molecular structure-physical property-device performance relationship has
      been established to highlight the importance of symmetrical structure in TADF
      host material design.

PMID- 29600700
TI  - Separation of Branched Poly(bisphenol A carbonate) Structures by Solvent Gradient
      at Near-Critical Conditions and Two-Dimensional Liquid Chromatography.
AB  - Branching is a molecular metric that strongly influences the application
      properties of polymers. Consequently, detailed information on the microstructure
      is required to gain a deeper understanding of structure-property relationships.
      In the present case, we employ high-performance liquid chromatography to
      characterize the branching in a poly(bisphenol A carbonate) (PC). To this end, a
      method was developed based on a mobile phase gradient in a very narrow range (+/
      1.4 vol %) around the point of adsorption (98.9/1.1 vol % chloroform/methyl tert
      butyl ether), which we refer to as solvent gradient at near-critical conditions.
      Application of such gentle gradient enabled separation of PC according to end
      groups. The separation mechanism was confirmed by collecting fractions of a
      separated sample and subsequently analyzing these by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Hyphenating the developed
      gradient method with size-exclusion chromatography as the second dimension (2D
      LC) enabled separation of linear and branched PC chains and determination of the
      molar mass distribution of the fractions. A reversed elution order was observed
      for branched species in 2D-LC, meaning that low molar mass chains exhibited
      higher elution volumes in the first dimension than higher molar masses. This
      finding was explained by influences of end-groups as well as the architecture of
      the branched polymer chains.

PMID- 29600701
TI  - Flexible Multifunctional Aromatic Polyimide Film: Highly Efficient
      Photoluminescence, Resistive Switching Characteristic, and Electroluminescence.
AB  - We report a flexible multifunctional aromatic polyimide (BTDBPI) that shows
      yellow-green fluorescence with high photoluminescence quantum yield (PLQY) of 30%
      in the film state. The nonvolatile "write once-read many" (WORM) characteristic
      in a memory device with the configuration of ITO/BTDBPI/Au indicates that BTDBPI
      possesses organic semiconductor behavior. Moreover, polymer light-emitting diodes
      (PLEDs) with the structure of ITO/PEDOT:PSS/BTDBPI/TPBI/Mg-Ag exhibits an
      interesting dual-emission phenomenon that originates from the electroluminescence
      (EL) of the BTDBPI nanometer film (yellow-green, 525 nm) and TPBI (deep blue, 380
      nm), demonstrating that BTDBPI shows both the charge-transporting and EL
      properties.

PMID- 29600702
TI  - Bronsted-Acid-Promoted Rh-Catalyzed Asymmetric Hydrogenation of N-Unprotected
      Indoles: A Cocatalysis of Transition Metal and Anion Binding.
AB  - The incorporation of Bronsted acid, thiourea anion binding, and transition metal
      catalysis enables an efficient method to synthesize chiral indolines via
      hydrogenation of indoles. Catalyzed by a rhodium/ZhaoPhos complex, asymmetric
      hydrogenation of unprotected indoles is performed smoothly with excellent
      enantioselectivities (up to 99% ee, up to 400 TON). Bronsted acid HCl activates
      indoles to form iminium ion intermediates. Mechanistic studies support the
      assumption that anion binding plays a crucial role as a secondary interaction.
      DFT calculations reveal an outer-sphere mechanism in this chemical
      transformation.

PMID- 29600703
TI  - BODIPY-Based Two-Photon Fluorescent Probe for Real-Time Monitoring of Lysosomal
      Viscosity with Fluorescence Lifetime Imaging Microscopy.
AB  - The viscosity of lysosome is reported to be a key indicator of lysosomal
      functionality. However, the existing mechanical methods of viscosity measurement
      can hardly be applied at the cellular or subcellular level. Herein, a BODIPY
      based two-photon fluorescent probe was presented for monitoring lysosomal
      viscosity with high spatial and temporal resolution. By installing two morpholine
      moieties to the fluorophore as target and rotational groups, the TICT effect
      between the two morpholine rings and the main fluorophore scaffold endowed the
      probe with excellent viscosity sensitivity. Moreover, Lyso-B succeeded in showing
      the impact of dexamethasone on lysosomal viscosity in real time.

PMID- 29600704
TI  - Formation of Strong Basicity on Covalent Triazine Frameworks as Catalysts for the
      Oxidation of Methylene Compounds.
AB  - Porous solid bases are increasingly attractive for applications in green
      chemistry and heterogeneous catalysis under relatively mild conditions. Here,
      covalent triazine frameworks (CTFs) were first applied as a support for the
      porous solid strong bases through a redox process between the base precursor KNO3
      and CTFs, leading to a relatively low calcination temperature (400  degrees C).
      As a result, porous organic frameworks possessing ordered microstructures as well
      as strong basic sites were successfully synthesized. The materials were
      characterized by X-ray diffraction, Fourier transform infrared, high-resolution
      transmission electron microscopy, temperature programmed desorption of CO2, and
      so forth. The obtained solid bases displayed remarkable catalytic activity in the
      aerobic oxidation of methylene compounds, and the yield of fluorenones could
      reach 93.6% at 120  degrees C, which was nearly 3 times higher than that of the
      control catalyst. The current research may present a new idea for the
      construction of porous organic polymers with strong basicity.

PMID- 29600705
TI  - Transforming Monolayer Transition-Metal Dichalcogenide Nanosheets into One
      Dimensional Nanoscrolls with High Photosensitivity.
AB  - One-dimensional (1D) nanoscrolls derived from two-dimensional (2D) nanosheets own
      unusual physical and chemical properties that arise from the spiraled 1D
      morphology and the atomic thin 2D building blocks. Unfortunately, preparation of
      large-sized nanoscrolls of transition-metal dichalcogenides (TMDCs) remains a big
      challenge, which greatly restricts the fabrication of single-scroll devices for
      their fundamental studies and further applications. In this work, we report a
      universal and facile method, by making use of the evaporation process of volatile
      organic solvent, to prepare TMDC (e.g., MoS2 and WS2) nanoscrolls with lengths of
      several tens to one hundred micrometers from their 2D precursors presynthesized
      by chemical vapor deposition on Si/SiO2. Both atomic force microscopy and
      electron microscopy characterizations confirmed the spirally rolledup structure
      in the resulting nanoscrolls. An interlayer spacing of as small as ~0.65 nm was
      observed, suggesting the strong coupling between adjacent layers, which was
      further evidenced by the emergence of new breathing mode peaks in the ultralow
      frequency Raman spectrum. Importantly, compared with the photodetector fabricated
      from a monolayer MoS2 or WS2 nanosheet, the device based on an MoS2 or WS2
      nanoscroll showed the much enhanced performance, respectively, with the
      photosensitivity greatly increased up to 2 orders of magnitude. Our work suggests
      that turning 2D TMDCs into 1D scrolls is promising in achieving high performances
      in various electronic/optoelectronic applications, and our general method can be
      extended to the preparation of large-sized nanoscrolls of other kinds of 2D
      materials that may bring about new properties and phenomena.

PMID- 29600706
TI  - Accelerating the Pace of Chemical Risk Assessment.
AB  - Changes in chemical regulations worldwide have increased the demand for new data
      on chemical safety. New approach methodologies (NAMs) are defined broadly here as
      including in silico approaches and in chemico and in vitro assays, as well as the
      inclusion of information from the exposure of chemicals in the context of hazard
      [European Chemicals Agency, " New Approach Methodologies in Regulatory Science ",
      2016]. NAMs for toxicity testing, including alternatives to animal testing
      approaches, have shown promise to provide a large amount of data to fill
      information gaps in both hazard and exposure. In order to increase experience
      with the new data and to advance the applications of NAM data to evaluate the
      safety of data-poor chemicals, demonstration case studies have to be developed to
      build confidence in their usability. Case studies can be used to explore the
      domains of applicability of the NAM data and identify areas that would benefit
      from further research, development, and application. To ensure that this science
      evolves with direct input from and engagement by risk managers and regulatory
      decision makers, a workshop was convened among senior leaders from international
      regulatory agencies to identify common barriers for using NAMs and to propose
      next steps to address them. Central to the workshop were a series of
      collaborative case studies designed to explore areas where the benefits of NAM
      data could be demonstrated. These included use of in vitro bioassays data in
      combination with exposure estimates to derive a quantitative assessment of risk,
      use of NAMs for updating chemical categorizations, and use of NAMs to increase
      understanding of exposure and human health toxicity of various chemicals. The
      case study approach proved effective in building collaborations and engagement
      with regulatory decision makers and to promote the importance of data and
      knowledge sharing among international regulatory agencies. The case studies will
      be continued to explore new ways of describing hazard (i.e., pathway
      perturbations as a measure of adversity) and new ways of describing risk (i.e.,
      using NAMs to identify protective levels without necessarily being predictive of
      a specific hazard). Importantly, the case studies also highlighted the need for
      increased training and communication across the various communities including the
      risk assessors, regulators, stakeholders (e.g., industry, non-governmental
      organizations), and the general public. The development and application of NAMs
      will play an increasing role in filling important data gaps on the safety of
      chemicals, but confidence in NAMs will only come with learning by doing and
      sharing in the experience.

PMID- 29600707
TI  - Characteristics of Polybrominated Diphenyl Ethers Released from Thermal Treatment
      and Open Burning of E-Waste.
AB  - Primitive processing of e-waste potentially releases abundant organic
      contaminants to the environment, but the magnitudes and mechanisms remain to be
      adequately addressed. We conducted thermal treatment and open burning of typical
      e-wastes, that is, plastics and printed circuit boards. Emission factors of the
      sum of 39 polybrominated diphenyl ethers (?39PBDE) were 817-1.60 * 105 ng g-1 in
      thermal treatment and nondetected-9.14 * 104 ng g-1, in open burning. Airborne
      particles (87%) were the main carriers of PBDEs, followed by residual ashes (13%)
      and gaseous constituents (0.3%), in thermal treatment, while they were 30%, 43%
      and 27% in open burning. The output-input mass ratios of ?39PBDE were 0.12-3.76
      in thermal treatment and 0-0.16 in open burning. All PBDEs were largely
      affiliated with fine particles, with geometric mean diameters at 0.61-0.83 MUm in
      thermal degradation and 0.57-1.16 MUm in open burning from plastic casings, and
      0.44-0.56 and nondetected- 0.55 MUm, from printed circuit boards. Evaporation and
      reabsorption may be the main emission mechanisms for lightly brominated BDEs, but
      heavily brominated BDEs tend to affiliate with particles from heating or
      combustion. The different size distributions of particulate PBDEs in emission
      sources and adjacent air implicated a noteworthy redisposition process during
      atmospheric dispersal.

PMID- 29600708
TI  - Umpolung Reaction of alpha-Imino Thioesters and the Subsequent C-C Bond Formation
      with the Unexpected Alkylthio Rearrangement.
AB  - An umpolung reaction of the alpha-imino thioester was examined, and we found that
      alpha-imino thioesters were more effective substrates for the umpolung N
      alkylation than conventional alpha-imino esters and they gave N-alkylated amino
      thioesters in high yields under mild reaction conditions in a short time. A new
      type of C-C bond formation followed by an unexpected rearrangement of the
      alkylthio group took place with the unsaturated ketones to afford the beta
      alkylthio-alpha-amino thioesters in high yields with good diastereoselectivity.

PMID- 29600709
TI  - Development of a Synthetic Method for Multifunctionalized Pyrroles Using
      Isocyanide Dichloride as a Key Intermediate.
AB  - Multifunctionalized pyrrole derivatives were synthesized using a highly efficient
      method based on the Michael addition of carbanions generated in situ from
      isocyanide dichloride to alpha,beta-unsaturated carbonyl compounds. The reactions
      proceeded smoothly to afford the pyrrole derivatives in good to high yields. A
      wide range of Michael acceptors, such as alpha,beta-unsaturated carbonyl
      compounds and nitroolefin, were successfully applied to this reaction.

PMID- 29600710
TI  - Synthesis of alpha-Methylene-beta-lactams Enabled by Base-Promoted Intramolecular
      1,2-Addition of N-Propiolamide and C-C Bond Migrating Cleavage of Aziridine.
AB  - A formal alpha-addition of N-propiolamide and 2-bromoacetate is reported for the
      synthesis of alpha-methylene-beta-lactam in good yields. The transformation
      proceeds smoothly in the presence of K2CO3 as a base and KI as an additive. An
      excellent reaction scope is observed. A 2 mmol scaled synthesis of alpha
      methylene-beta-lactams and synthetic applications of alpha-methylene-beta-lactams
      are also reached. In the process, it is believed that an intramolecular 1,2
      addition of N-propiolamide and sequential C-C bond migrating cleavage are
      involved.

PMID- 29600711
TI  - JQ-1 Inhibits Colon Cancer Proliferation via Suppressing Wnt/beta-Catenin
      Signaling and miR-21.
AB  - Bromodoamin and extraterminal (BET) protein inhibitors are a novel class of
      cancer therapeutics. Here we aim to investigate the efficacy and mechanism of JQ
      1, a potent BET inhibitor, in colon cancer therapy. JQ-1 was used to treat SW480
      colon cancer mouse xenografts. The tumor size and mouse survival were recorded.
      Cell apoptosis was evaluated by Annex V-FIC/PI flow cytometry. ChIP-q-PCR
      analysis was used to assess the H3K27 trimethylation (H3K27m3) of the p16
      promoter. Wnt signaling was evaluated by Nkd2 and beta-catenin levels. RT-PCR was
      used to evaluate the level of miR-21. MiR-21 was overexpressed with a lentiviral
      system and was used to evaluate the relationship between miR-21 and JQ-1. JQ-1
      significantly reduced tumor growth, improved mouse survival, and induced
      apoptosis. JQ-1 epigenetically inhibited the H3K27me3 promoter activity,
      promoting p16 expression. Nkd2 and beta-catenin were upregulated and
      downregulated by JQ-1, respectively. MiR-21 was downregulated by JQ-1. MiR-21
      overexpression compensated for proliferation inhibition by JQ-1. Nkd2 levels were
      also downregulated by miR-21 overexpression. JQ-1 is effective in inhibiting
      colon cancer. We revealed that the mechanism of JQ-1 action is associated with
      its regulation of Wnt/beta-catenin signaling and miR-21 levels.

PMID- 29600712
TI  - Molecular Dynamics Simulations of Orai Reveal How the Third Transmembrane Segment
      Contributes to Hydration and Ca2+ Selectivity in Calcium Release-Activated
      Calcium Channels.
AB  - Calcium release-activated calcium (CRAC) channels open upon depletion of Ca2+
      from the endoplasmic reticulum, and when open, they are permeable to a selective
      flux of calcium ions. The atomic structure of Orai, the pore domain of CRAC
      channels, from Drosophila melanogaster has revealed many details about conduction
      and selectivity in this family of ion channels. However, it is still unclear how
      residues on the third transmembrane helix can affect the conduction properties of
      the channel. Here, molecular dynamics and Brownian dynamics simulations were
      employed to analyze how a conserved glutamate residue on the third transmembrane
      helix (E262) contributes to selectivity. The comparison between the wild-type and
      mutated channels revealed a severe impact of the mutation on the hydration
      pattern of the pore domain and on the dynamics of residues K270, and Brownian
      dynamics simulations proved that the altered configuration of residues K270 in
      the mutated channel impairs selectivity to Ca2+ over Na+. The crevices of water
      molecules, revealed by molecular dynamics simulations, are perfectly located to
      contribute to the dynamics of the hydrophobic gate and the basic gate, suggesting
      a possible role in channel opening and in selectivity function.

PMID- 29600713
TI  - Template Synthesis of an Ultrathin beta-Graphdiyne-Like Film Using the Eglinton
      Coupling Reaction.
AB  - beta-Graphdiyne (beta-GDY) is a two-dimensional carbon material with zero band
      gap and highly intrinsic carrier mobility and a promising material with potential
      applications in electronic devices. However, the synthesis of continuous single
      or ultrathin beta-GDY has not been realized yet. Here, we proposed an approach
      for ultrathin beta-GDY-like film synthesis using graphene as a template because
      of the strong pi-pi interaction between beta-GDY and graphene. The as-synthesized
      film presents smooth and continuous morphology and has good crystallinity.
      Electrical measurement reveals that the film presented a conductivity of 1.30 *
      10-2 S.m-1 by fabricating electronic devices on beta-GDY grown on a dielectric
      hexagonal boron nitride template.

PMID- 29600714
TI  - Regio- and Stereoselective Copper-Catalyzed Allylation of 1,3-Dicarbonyl
      Compounds with Terminal Allenes.
AB  - Simple ligand-free copper systems were found as efficient catalysts for the
      addition of 1,3-dicarbonyl compounds to N-allenyl derivatives. This highly regio-
      and stereoselective reaction has been accomplished in the presence of malonates,
      1,3-ketoesters, and 1,3-diketones with good to excellent yields under mild
      conditions. This methodology represents the first allylation of 1,3-dicarbonyl
      compounds with allenes catalyzed by copper.

PMID- 29600715
TI  - Olanzapine-induced photo-allergic reaction.

PMID- 29600716
TI  - A contribution to the elemental profile of the leaf samples of newly developed
      Cabernet Franc varieties.
AB  - The elemental profile of the leaf samples of three Cabernet Franc clone
      candidates recently developed in Serbia (Nos. 02, 010 and 012) obtained in the
      last phase of clonal selection was examined within this study by ICP-OES. Optimal
      content of Al, Fe, Cu and Zn, the metals well known for their links with a number
      of neurodegenerative disorders including Alzheimer's disease, has actually
      highlighted the potential of the leaf sample No. 10 to afford a novel food
      supplement of natural origin possessing well balanced metal ingredients.
      Furthermore, lower content of some other elements (Cr, Mn, Ni and Pb) thoroughly
      supports such a claiming. Finally, the most favourable K/Na ratio observed for
      the aforementioned sample points out its likely cardioprotectivity. However, two
      other Cabernet Franc clone candidates might also be recommended for breeding in
      the same or similar viticultural conditions, since all obtained values were below
      toxic ones for human consumption.

PMID- 29600717
TI  - Secondary metabolites from Antarctic marine-derived fungus Penicillium crustosum
      HDN153086.
AB  - A new polyene compound (1) and a new diketopiperazine (2), as well as three known
      compounds (3-5), were isolated from the Antarctic marine-derived fungus
      Penicillium crustosum HDN153086. The structures of 1-5 were deduced based on MS,
      NMR and TD-DFT calculations of specific ECD spectra. These compounds were
      evaluated for their cytotoxic activities against K562 cell line and only compound
      2 exhibited cytotoxicity against K562 cell, with IC50 value of 12.7 MUM.

PMID- 29600718
TI  - Synthesis, characterization, and biological evaluations of some steryl 2
      methoxybenzoates as anticancer agents.
AB  - Using cholesterol, stigmasterol and sitosterol as starting materials, a series of
      7-subsitituted-ster-3-yl 2-methoxybenzoate analogs were prepared through reacting
      with 2-methoxybenzoyl chloride and introducing some function groups, such as
      carbonyl, hydroxyl and various thiosemicarbazones, at 7-position of steroidal
      nucleus. The structures of these new compounds were characterized by IR, NMR and
      HRMS. Their antiproliferative activities were evaluated by using several types of
      cancer cells. Interestingly, the compounds displayed potent antiproliferative
      activity against CNE-2 (nasopharyngeal carcinoma cell lines), BEL-7402 (human
      liver cancer cell lines) and HepG2 (human liver cancer cell lines), suggesting
      that they have potential to be drug candidates for cancer treatment.

PMID- 29600719
TI  - Comparison of Plantar Fasciitis Injected With Platelet-Rich Plasma vs
      Corticosteroids.
AB  - BACKGROUND: Plantar fasciitis is one of the most common causes of heel pain. This
      prospective study compared the efficacy of local injection of corticosteroids vs
      platelet-rich plasma (PRP) in the treatment of plantar fasciitis. METHODS:
      Patients were randomly allocated into 2 groups of 40 each (group A and group B).
      Patients were treated with local corticosteroid injection in group A and
      autologous PRP injection in group B. Clinical assessment was done prior to the
      injection and at 1 month, 3 months, and 6 months following the injection, which
      included visual analog pain scale, subjective rating using the modified Roles and
      Maudsley score, functional outcome score by the Foot and Ankle Outcome Instrument
      (FAI) core scale, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle
      hindfoot scale. Radiological assessment was done by measuring the thickness of
      the plantar fascia using ultrasonography. The mean age, sex, and body mass index
      of both groups were comparable. RESULTS: Postinjection, there was significant
      improvement of visual analog score, modified Roles and Maudsley score, FAI core
      scale, AOFAS ankle-hindfoot score, and plantar fascia thickness in both the
      groups. However, with the numbers available, no significant difference in
      improvement could be detected between the above-mentioned variables in the 2
      groups. CONCLUSION: We found that the treatment of plantar fasciitis with steroid
      or PRP injection was equally effective. LEVEL OF EVIDENCE: Level II, prospective
      randomized comparative series.

PMID- 29600720
TI  - Effect of Ankle Position on Tibiotalar Motion With Screw Fixation of the Distal
      Tibiofibular Syndesmosis in a Fracture Model.
AB  - BACKGROUND: Anatomic reduction and fixation of the syndesmosis in traumatic
      injuries is paramount in restoring function of the tibiotalar joint. While
      overcompression is a potential error, recent work has called into question
      whether ankle position during fixation really matters in this regard. Our study
      aimed to corroborate more recent findings using a fracture model that, to our
      knowledge, has not been previously tested. METHODS: Twenty cadaver leg specimens
      were obtained and prepared. Each was tested for tibiotalar motion under various
      conditions: intact syndesmosis, intact syndesmosis with lag screw compression,
      pronation external rotation type 4 (PER-4) ankle fracture with syndesmotic
      disruption, and single-screw syndesmotic fixation followed by plate and screw
      fracture and syndesmotic screw fixation. In each situation, the ankle was held in
      alternating plantarflexion and dorsiflexion when inserting the syndesmotic screw
      with the subsequent amount of maximal dorsiflexion being recorded following hand
      tight lag screw fixation. RESULTS: While ankle range of motion increased
      significantly with creation of the PER-4 injury, under no condition was there a
      statistically significant change in maximal dorsiflexion angle. CONCLUSION: Ankle
      position during distal tibiofibular syndesmosis fixation did not limit
      dorsiflexion of the ankle joint. CLINICAL RELEVANCE: Our findings suggest that
      maximal dorsiflexion during syndesmotic screw fixation may not be necessary.

PMID- 29600721
TI  - Optimized protocol for multigram preparation of emodin anthrone, a precursor in
      the hypericin synthesis.
AB  - Emodin reduction to emodin anthrone comprise one of three process steps involved
      in the hypericin synthesis, a powerful natural photosensitiser found in plants of
      the genus Hypericum. In this communication, an optimized protocol was established
      for emodin reduction enabling an efficient multigram preparation of emodin
      anthrone. A screening of reducing agent (SnCl2.2H2O and HClconc) under different
      reaction times was employed in micro-scale and monitored by electronic absorption
      spectroscopy technique. Data showed lower yields of emodin anthrone when some
      experimental conditions previously described in the literature were reproduce.
      However, using the optimized protocol for the emodin reduction these yields were
      overcoming, and a gram-scale supply experiment was reproducible for the
      preparation of 10 grams of emodin anthrone with excellent yield.

PMID- 29600722
TI  - The current illusion of educational inclusion.

PMID- 29600723
TI  - 'Civil skepticism' and the social construction of knowledge: A case in
      dendroclimatology.
AB  - Early Science and Technology Studies (STS) scholars recognized that the social
      construction of knowledge depends on skepticism's parasitic relationship to
      background expectations and trust. Subsequent generations have paid less
      empirical attention to skepticism in science and its relationship with trust. I
      seek to rehabilitate skepticism in STS - particularly, Merton's view of
      skepticism as a scientific norm sustained by trust among status peers - with a
      study of what I call 'civil skepticism'. The empirical grounding is a case in
      contemporary dendroclimatology and the development of a method ('Blue Intensity')
      for generating knowledge about climate change from trees. I present a sequence of
      four instances of civil skepticism involved in making Blue Intensity more
      resistant to critique, and hence credible (in laboratory experiments, workshops,
      conferences, and peer-review of articles). These skeptical interactions depended
      upon maintaining communal notions of civility among an increasingly extended
      network of mutually trusted peers through a variety of means: by making Blue
      Intensity complementary to existing methods used to study a diverse natural world
      (tree-ring patterns) and by contributing to a shared professional goal (the study
      of global climate change). I conclude with a sociological theory about the role
      of civil skepticism in constituting knowledge-claims of greater generality and
      relevance.

PMID- 29600724
TI  - Localization of Intracranial Lesions Using Superficial Stereotaxic Cranial Lesion
      Locator Based on Magnetic Resonance Images.
AB  - BACKGROUND: Detection of a deep-seated lesion located in the brain parenchyma and
      major neuroanatomical sites is a critical issue in neurosurgery. Some
      neurosurgical cranial navigation systems have been developed that are available;
      however, some preparation is necessary, including the installation of complex
      computer software programs and obtaining specific neuroradiological images.
      OBJECTIVE: The purpose of this experimental study was to design and evaluate a
      superficial stereotaxic frameless lesion locator in order to localize mass
      lesions within the brain. METHODS: A superficial stereotaxic frameless lesion
      locator system was designed using cardboard and the Cartesian coordinate system
      as a reference framework. This material was used in a model creating printed
      magnetic resonance images in the superficially marking of the lesion. This
      material easily located the lesion placement and superficially projected the
      lesion location. RESULTS: The results of this study revealed that the superficial
      stereotaxic frameless lesion location procedure using a coordinate cardboard
      locator is a safe, fast, and simple procedure. This procedure provides an
      accurate means of locating the target lesion seated within the brain parenchyma.
      When compared with other models, we found that this device is reliable and has a
      high rate of superficial lesion detection. CONCLUSION: A superficial lesion
      locator may be used in clinical practice. This experimental study demonstrated
      the usability and reliability of the procedure. Additional detailed
      investigations are necessary to improve the procedure.

PMID- 29600725
TI  - Overview of Impella and mechanical devices in cardiogenic shock.
AB  - INTRODUCTION: Cardiogenic shock (CS) is a life-threatening condition associated
      with significant morbidity and mortality. The Impella (Abiomed Inc.) is an axial
      flow pump on a pigtail catheter that is placed across the aortic valve to unload
      the left ventricle by delivering non-pulsatile blood flow to the ascending aorta.
      It is used for high-risk percutaneous coronary intervention and CS. Areas
      covered: Percutaneous mechanical support devices are placed in a minimally
      invasive manner and provide life-saving assistance. We review Impella and other
      percutaneous devices such as intra-aortic balloon pump, TandemHeart, and
      extracorporeal membrane oxygenation (ECMO) and the evidence supporting their use
      in the setting of CS. Expert commentary: Impella has been proven to be safe and
      may be superior to other mechanical support devices in CS.

PMID- 29600726
TI  - Aerobic With Resistance Training or Aerobic Training Alone Poststroke: A
      Secondary Analysis From a Randomized Clinical Trial.
AB  - BACKGROUND: Stroke is associated with muscle atrophy and weakness, mobility
      deficits, and cardiorespiratory deconditioning. Aerobic and resistance training
      (AT and RT) each have the potential to improve deficits, yet there is limited
      evidence on the utility of combined training. OBJECTIVE: To examine the effects
      of AT+RT versus AT on physiological outcomes in chronic stroke with motor
      impairments. METHODS: Participants (n = 73) were randomized to 6 months of AT (5
      d/wk) or AT+RT (3 and 2 d/wk, respectively). Outcomes included those related to
      body composition by dual-energy X-ray absorptiometry, mobility (6-minute walk
      distance [6MWD], sit-to-stand, and stair climb performance), cardiorespiratory
      fitness (VO2peak, oxygen uptake at the ventilatory threshold [VO2VT]), and
      muscular strength. RESULTS: A total of 68 (93.2%) participants (age, mean +/- SD
      = 63.7 +/- 11.9) completed the study. AT+RT and AT yielded similar and
      significant improvements in 6MWD (39.9 +/- 55.6 vs 36.5 +/- 63.7 m, P = .8),
      VO2peak (16.4% +/- 43.8% vs 15.2% +/- 24.7%, P = .9), sit-to-stand time (-2.3 +/-
      5.1 vs 1.02 +/- 9.5 s, P = .05), and stair climb performance (8.2% +/- 19.6% vs
      7.5% +/- 23%, P = .97), respectively. AT+RT produced greater improvements than AT
      alone for total body lean mass (1.23 +/- 2.3 vs 0.27 +/- 1.6 kg, P = .039),
      predominantly trunk ( P = .02) and affected-side limbs ( P = .04), VO2VT (19.1%
      +/- 26.8% vs 10.5% +/- 28.9%, P = .046), and upper- and lower-limb muscular
      strength ( P < .03, all except affected-side leg). CONCLUSION: Despite being
      prescribed 40% less AT, AT+RT resulted in similar and significant improvement in
      mobility and VO2peak, superior improvements in VO2VT and muscular strength, and
      an almost 5-fold greater increase in lean mass compared with AT. RT is the most
      neglected exercise component following stroke but should be prescribed with AT
      for metabolic, cardiorespiratory, and strength recovery.

PMID- 29600727
TI  - Clinical and neonatal outcomes of intrauterine insemination with frozen donor
      sperm.
AB  - : This retrospective study evaluated the association between frozen donor sperm
      used for intrauterine insemination and clinical and neonatal outcomes, including
      304 singleton pregnancies resulting from artificial insemination by the husband
      (AIH) and 173 singleton pregnancies resulting from artificial insemination by a
      donor (AID). The clinical outcomes for AID showed no increased risk of abortion,
      ectopic pregnancy or pregnancy complications compared to those for AIH. There
      were no differences in gender, gestational age or prematurity of live births
      between the two groups. However, the birthweight of live births from AID was
      significantly higher than that from AIH. Moreover, the AID group exhibited no
      increased risk of stillbirths or fetal defects compared to the AIH group. These
      results indicate that frozen donor sperm did not increase the occurrence of
      adverse clinical and neonatal outcomes when compared to sperm from the husband.
      ABBREVIATIONS: AID: artificial insemination by a donor; AIH: artificial
      insemination by the husband; ART: assisted reproduction technology; FET: frozen
      embryo transfer; IVF: in vitro fertilization; ICSI: intracytoplasmic sperm
      injection; IUI: intrauterine insemination; LBW: low birth weight.

PMID- 29600728
TI  - Cardiotrophin-1 as a new metabolic biomarker in women with PCOS.
AB  - The objective of this study was to investigate cardiotrophin-1 (CT-1) levels as a
      new metabolic biomarker in women with polycystic ovary syndrome (PCOS). One
      hundred consecutive women with PCOS were divided into two groups according to
      presence of metabolic syndrome as MetS+ and MetS-. Clinical, hormonal and
      metabolic parameters in addition to CT-1 levels were compared between the groups.
      Correlation analyses were performed between CT-1 and clinical and metabolic
      parameters in women with PCOS. One hundred PCOS subjects were enrolled in the
      study, of which 29 subjects were diagnosed with metabolic syndrome. WHR, systolic
      and diastolic blood pressures, triglyceride, total cholesterol, HOMA-IR, FAI, FGS
      and CT-1 levels were significantly higher in the MetS+ group compared with the
      MetS- group. HDL cholesterol was significantly higher in the MetS- group than the
      MetS+ one. CT-1 levels were found to be positively correlated with diastolic
      blood pressure, TG levels and FGS. Cardiotrophin-1 may be a promising new
      metabolic biomarker in women with PCOS. CT-1 may be beneficial for estimating the
      risk of long-term adverse health consequences and establishing early intervention
      and preventation strategies.

PMID- 29600729
TI  - Astroglial 5-HT2B receptor in mood disorders.
AB  - INTRODUCTION: Astroglia represent the main cellular homeostatic system of the
      central nervous system (CNS). Astrocytes are intimately involved in regulation
      and maintenance of neurotransmission by regulating neurotransmitters removal and
      turnover and by supplying neurons with neurotransmitters precursors. Astroglial
      cells are fundamental elements of monoaminergic transmission in the brain and in
      the spinal cord. Astrocytes receive monoaminergic inputs and control catabolism
      of monoamines through dedicated transporters and intracellular enzymatic
      pathways. Areas covered: Astroglial cells express serotonergic receptors; in this
      review, we provide an in-depth characterization of 5-HT2B receptors. Activation
      of these receptors triggers numerous intracellular signaling cascades that
      regulate expression of multiple genes. Astroglial 5-HT2B receptors are activated
      by serotonin-specific reuptake inhibitors, such as major anti-depressant
      fluoxetine. Expression of astroglial serotonin receptors undergoes remarkable
      changes in depression disorders, and these changes can be corrected by chronic
      treatment with anti-depressant drugs. Expert commentary: Depressive behaviors,
      which occur in rodents following chronic stress or in neurotoxic models of
      Parkinson disease, are associated with significant changes in the expression of
      astroglial, but not neuronal 5-HT2B receptors; while therapy with anti
      depressants normalizes both receptors expression and depressive behavioral
      phenotype. In summary, astroglial serotonin receptors are linked to mood
      disorders and may represent a novel target for cell- and molecule-specific
      therapies of depression and mood disorders.

PMID- 29600730
TI  - Memory bias toward emotional information in burnout and depression.
AB  - A sample of 1015 educational staff members, exhibiting various levels of burnout
      and depressive symptoms, underwent a memory test involving incident encoding of
      positive and negative words and a free recall task. Burnout and depression were
      each found to be associated with increased recall of negative items and decreased
      recall of positive items. Results remained statistically significant when
      controlling for history of depressive disorders. Burnout and depression were not
      related to mistakes in the reported words, or to the overall number of recalled
      words. This study suggests that burnout and depression overlap in terms of memory
      biases toward emotional information.

PMID- 29600731
TI  - The diagnosis is correct, but National Institute of Health and Care Excellence
      guidelines are part of the problem not the solution.
AB  - Mike Scott's study provides data demonstrating that the national Improving Access
      to Psychological Therapies project is not leading to improved outcomes or value
      for money. I present further data from both the adult and children and young
      people's versions of Improving Access to Psychological Therapies that lends
      supports to this conclusion. However, while Scott argues in favour of better
      compliance with National Institute of Health and Care Excellence guidelines and
      greater model expertise, I argue that it is this 'technical' focus that is part
      of the problem not the solution.

PMID- 29600732
TI  - Five macrocyclic glycosides from Schoenoplectus tabernaemontani.
AB  - Macrocyclic glycosides with unique 22-membered dimeric lactone skeleton, are rare
      occurring natural products. There are only ten compounds reported so far. Herein
      we reported the isolation and characterisation of five macrocyclic glycosides
      from Schoenoplectus tabernaemontani, including three new compounds (Schoenopolide
      A-C, 1-3) and two known ones, Berchemolide (4) and Clemoarmanoside B (5). Their
      structures were established on the basis of extensive analysis of spectroscopic
      data. In addition, the anti-oxidative activity of Berchemolide (4) against H2O2
      induced of renal tubular epithelial (HK-2) cells was also evaluated.

PMID- 29600733
TI  - Society and 'good woman': A critical review of gender difference in depression.
AB  - BACKGROUND: Worldwide, women are found to suffer from depression significantly
      more than men. This has puzzled the scientists since no biological explanation
      can completely resolve the matter. METHOD: Extant empirical work has been
      conducted to solve the mystery of the issue. However, most of the research has
      pivoted their attention to biology. Therefore, based on the previous literature
      from the disciplines of medicine, psychology and sociology, the author aimed at
      looking and reviewing the matter critically. Specifically, the present critical
      review aims at conceptualising the psychological, social and cultural factors in
      the context of gender difference in depression. DISCUSSION: The work reveals that
      psychological variables such as women's unique attachment patterns, relational
      self-construal, as well as a macro-level issue like power dynamics based on
      gender, and the skewed division of labour play an important role in gender
      difference in depression. The work also suggests that focusing solely on
      biological underpinnings may result in losing the entire scenario; therefore,
      social and cultural issues that place women in a socially disadvantaged position
      are equally important.

PMID- 29600734
TI  - Inhalation therapy for repairing damaged elastin fibers and decelerating
      elastinolysis in chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Current pharmacologic therapy of chronic obstructive pulmonary
      disease (COPD) can reduce respiratory symptoms and exacerbation frequency.
      However, no single COPD intervention except for lung transplantation has proven
      effective in recovering lung function. Lung elasticity is reduced in COPD lungs,
      which is for a large part due to chronically enhanced elastin degradation.
      Elastin calcification and formation of advanced glycation end products (AGEs) may
      also contribute to this. Areas covered: We propose inhalation therapy to induce
      repair of damaged pulmonary elastin fibers by stimulating tropoelastin synthesis,
      assembly and crosslinking in order to improve lung function in patients with
      COPD. Decelerating elastinolysis is another treatment objective, as well as
      decalcification and deglycation of the extracellular matrix. Expert commentary:
      Studies should be conducted to test whether it is feasible to restore pulmonary
      elastin fibers with inhalation therapy. We expect that the optimal formulation
      will turn out to be a combination of copper, epigallocatechin-(3-)gallate or
      pentagalloyl glucose, vitamin A/D/K, magnesium, heparin or heparan sulfate,
      minoxidil and one or more AGEs inhibitors. Establishing a treatment that has the
      proven ability to facilitate regain of lost lung function in COPD patients would
      cause a major paradigm shift in this debilitating disease.

PMID- 29600735
TI  - Wastewater treatment for nutrient removal with Ecuadorian native microalgae.
AB  - The aim of this project was to study the feasibility of utilizing native
      microalgae for the removal of nitrogen and phosphorus, as a potential secondary
      wastewater treatment process in Ecuador. Agitation and aeration batch experiments
      were conducted using synthetic secondary wastewater effluent, to determine
      nitrogen and phosphorus removal efficiencies by a native Ecuadorian microalgal
      strain. Experimental results indicated that microalgal cultures could
      successfully remove nitrogen and phosphorus. [Formula: see text] and [Formula:
      see text] removal efficiencies of 52.6 and 55.6%, and 67.0 and 20.4%, as well as
      [Formula: see text] production efficiencies of 87.0 and 93.1% were reported in
      agitation and aeration photobioreactors, respectively. Aeration was not found to
      increase the nutrient removal efficiency of [Formula: see text]. Moreover, in the
      case of [Formula: see text], a negative impact was observed, where removal
      efficiencies decreased by a factor of 3.3 at higher aeration rates. To the best
      of our knowledge, this is the first report of the removal of nutrients by native
      Ecuadorian Chlorella sp., hence the results of this study would indicate that
      this native microalgal strain could be successfully incorporated in a potential
      treatment process for nutrient removal in Ecuador.

PMID- 29600736
TI  - Nutrient characterisation and bioenergy potential of common Nigerian food wastes.
AB  - Nigeria is the world's largest producer of yam, cassava, cocoyam/taro,
      beans/cowpea, egusi/melon seeds and among the largest producers of
      groundnut/peanut, plantain, corn/maize and ugwu/pumpkin leaves. These food crops
      generate unavoidable food wastes that can contribute to environmental degradation
      through unsanctioned waste disposal methods. Such food wastes can be utilised as
      feedstock for the anaerobic digestion (AD) process to produce renewable energy.
      In order to determine the suitability of the food wastes as biofuel feedstock,
      they were experimentally analysed. Their waste content was determined,
      characterised and used to evaluate their bio-methane potential. The tests were
      performed using standard proximate analytical methods while the bioenergy
      potential of the samples was determined using the Baserga model. Results
      indicated a specific waste index range of 0.2-1.5, with corn having the highest
      waste proportion. The proximate analysis results of the wastes were within the
      range of common AD feedstocks such as energy crops and plant by-products. The bio
      methane potentials of the samples varied widely with results ranging from 35-460
      m3 tonne-1 on fresh weight and (5.4-6.2) * 105 m3 kg-1 on volatile solid basis.
      The methane potential varied between 51% and 58% of produced biogas. The energy
      potential of the food wastes was 31 TWh yr-1 which can make a substantial
      contribution to the bioenergy production of the country and meet up to the energy
      demand of 4.7 * 107 Nigerian households. Further studies would be required to
      determine the actual biogas yields of the food wastes.

PMID- 29600737
TI  - Statin prescription rates and their facility-level variation in patients with
      peripheral artery disease and ischemic cerebrovascular disease: Insights from the
      Department of Veterans Affairs.
AB  - The 2013 American College of Cardiology/American Heart Association cholesterol
      guideline recommends moderate to high-intensity statin therapy in patients with
      peripheral artery disease (PAD) and ischemic cerebrovascular disease (ICVD). We
      examined frequency and facility-level variation in any statin prescription and in
      guideline-concordant statin prescriptions in patients with PAD and ICVD receiving
      primary care in 130 facilities across the Veterans Affairs (VA) health care
      system between October 2013 and September 2014. Guideline-concordant statin
      intensity was defined as the prescription of high-intensity statins in patients
      with PAD or ICVD <=75 years and at least moderate-intensity statins in those >75
      years. We calculated median rate ratios (MRR) after adjusting for patient
      demographic factors to assess the magnitude of facility-level variation in statin
      prescribing patterns independent of patient characteristics. Among 194,151 PAD
      patients, 153,438 patients (79.0%) were prescribed any statin and 79,435 (40.9%)
      were prescribed a guideline-concordant intensity of statin. PAD patients without
      ischemic heart disease were prescribed any statin and a guideline-concordant
      intensity of statin therapy less frequently (69.1% and 28.9%, respectively).
      Among 339,771 ICVD patients, 265,491 (78.1%) were prescribed any statin and
      136,430 (40.2%) were prescribed a guideline-concordant intensity of statin. ICVD
      patients without ischemic heart disease were prescribed any statin and a
      guideline-concordant intensity of statin less frequently (70.9% and 30.5%,
      respectively). MRRs for both PAD and ICVD patients demonstrated a 20% and 28%
      variation among two facilities in treating two identical patients with statin
      therapy and guideline-concordant intensity of statin therapy, respectively. The
      prescription of statins, especially guideline-recommended intensity of statin
      therapy, is suboptimal in PAD and ICVD patients, with significant facility-level
      variation not explained by patient-level factors.

PMID- 29600738
TI  - Under-utilization of statin medications in patients with peripheral artery
      disease or cerebrovascular disease.

PMID- 29600739
TI  - Images in Vascular Medicine: 'Popcorn in the heart': Thromboemboli in transit
      during acute pulmonary embolism.

PMID- 29600740
TI  - Sensitivity and Specificity Analysis: Use of Emoticon for Screening of Depression
      in Elderly in Singapore.
AB  - BACKGROUND: The current screening tools for depression can be tedious to
      administer, especially in the elderly population with hearing impairment and/or
      limited proficiency in English language. OBJECTIVES: To look at the feasibility
      of using emoticon as a screening and assessment tool for depression in the
      elderly. DESIGN: Cross-sectional study. METHOD: A total of 77 elderly patients
      completed the study from June 2014 to August 2015 in a general geriatric
      outpatient clinic of an acute care hospital in Singapore. Patients rated their
      mood using an emoticon scale, which ranges from 1 ( most happy face) to 7 ( most
      sad face). Depression was assessed using the Diagnostic and Statistical Manual of
      Mental Disorders (4th ed.; DSM-IV) criteria as the gold standard. Sensitivity and
      specificity for depression were calculated for the cutoff scores from 1 to 7 on
      the emoticon scale. RESULTS: The sensitivity percentages were low across all
      cutoff scores. The specificity was more than 90% for the cutoff score of 5 and
      above on the emoticon scale. However, all the patients who had depression
      diagnosed using the DSM-IV criteria did not have emoticon scores of 5 and above.
      CONCLUSIONS: The emoticon scale was easy to use, but its effectiveness in the
      screening of depression in the elderly needs to be explored further. The
      inability to use the emoticon scale as a tool may be the lack of measurements in
      the other domains of the DSM-IV criteria (sleep, energy, appetite, etc.), rather
      than failure of the emoticon scale to assess mood.

PMID- 29600741
TI  - Photocatalytic degradation of phenazopyridine contaminant in soil with direct
      solar light.
AB  - Photocatalytic degradation of waste pharmaceutics, with solar radiation, is
      described here as a feasible method to purify pre-contaminated soils.
      Phenazopyridine has been used as a model soil contaminant. Two different nano
      size powders have been first examined as catalysts, namely commercial TiO2
      (anatase) and commercial ZnO. As the ZnO showed higher catalytic efficiency, the
      study was then focused on it. The commercial ZnO powder was then compared with
      lab-prepared ZnO powder, and the latter shows relatively higher efficiency. The
      ZnO was used in two different ways. In one way, dry ZnO catalyst powder was
      spread onto the soil, while in the other way the ZnO was sprayed onto the soil
      surface by a wet spray method. The spray technique shows slightly higher
      efficiency, in addition to being easier to apply at future large scale. Depending
      on conditions and type of photocatalyst used, up to 90% contaminant removal can
      be achieved in 30 min. In case of photocatalysis experiments, the reacted
      contaminant molecules undergo complete degradation with no detectable side
      reaction organic products. Possible evaporation or escape of organic contaminant,
      or other possibly resulting organics, is ruled out by a series of control
      experiments. Photodegradation process takes place only at the catalytic sites on
      the soil surface, where contaminant molecules that diffuse from the soil bulk are
      completely degraded. Other useful organisms inside the soil are not affected as
      they are kept away from catalyst sites. A plausible mechanism is proposed for the
      degradation process.

PMID- 29600742
TI  - A new flavonoid from the leaves of Atalantia monophylla (L.) DC.
AB  - A new flavonoid, atalantraflavone (1) as well as eight known compounds including
      atalantoflavone (2), racemoflavone (3), 5,4'-dihydroxy-(3",4"-dihydro-3",4"
      dihydroxy)-2",2"-dimethylpyrano-(5",6":7,8)-flavone (4), lupalbigenin (5),
      anabellamide (6), citrusinine I (7), p-hydroxybenzaldehyde (8), and frideline
      (9), were isolated from the leaves of Atalantia monophylla (L.) DC. Focusing on
      Alzheimer's disease, acetylcholine esterase (AChE) inhibition and antioxidant
      activity were evaluated using the modified Ellman's method and the ABTS
      scavenging assay, respectively. It was found that isoflavonoid 5, lupalbigenin,
      showed 79% inhibition to AChE and was 1.4-fold stronger than the tacrine
      standard. In addition, acridone 7, citrusinine I, displayed 90.68% antioxidant
      activity.

PMID- 29600743
TI  - What types of recommendations are we giving patients? A survey of clinical
      neuropsychologists.
AB  - OBJECTIVE: To identify types of recommendations that neuropsychologists most
      frequently give to patients, and determine which specific recommendations are
      most and least consistently given to patients across and within different
      diagnostic populations. METHOD: A total of 309 clinical neuropsychologists
      completed a survey evaluating the frequency with which they made particular types
      of recommendations (e.g. driving, employment and education, health and
      rehabilitation referrals) to patients with various disorders (e.g. traumatic
      brain injury, dementia). RESULTS: Recommendations in some categories were common
      across diagnoses (e.g. recommendations related to health). Neuropsychologists
      reported being more likely to give patients with dementia (relative to other
      clinical populations) recommendations related to educational resources,
      supervision and independence, and driving. Patients with a TBI diagnosis were
      more likely to be given recommendations related to employment and education,
      health and rehabilitation referrals, and mental health and substance use.
      Patients with a psychiatric diagnosis were more likely to be given
      recommendations related to mental health and substance use. Irrespective of
      diagnosis, neuropsychologists reported being most likely to give recommendations
      that could be implemented by the patient or caregiver without assistance from
      outside sources. Neuropsychologists varied in their use of recommendations to
      seek evaluations and treatment from health and rehabilitation referrals and in
      providing recommendations related to driving. CONCLUSIONS: Recommendations
      provided within diagnostic groups are consistent with the etiology and prognosis
      of those conditions. Recommendations for the use of compensatory strategies to
      address cognitive deficits and recommendations to improve health were endorsed by
      the vast majority of neuropsychologists across diagnoses.

PMID- 29600744
TI  - Icelandic inclusion, German hesitation and American fear: A cross-cultural
      comparison of mental-health stigma and the media.
AB  - AIMS: Quantitative survey research findings reveal that Western countries have
      lower rates of public stigma surrounding mental illness than other nations.
      However, qualitative media research across selected Western countries reports
      differences in stigmatising messages. Here, we take an in-depth look at country
      level data exploring both similarities and differences in this stigma across
      three countries. Specifically, we use previous findings on global differences in
      public stigma and media to examine whether there is a correspondence between
      themes in newspaper reporting and variations in attitudes across seven stigma
      dimensions. METHODS: The Stigma in Global Context - Mental Health Study provides
      nationally representative data from Iceland ( N=1033; response rate=71%), Germany
      ( N=1255; response rate=63.16%) and the USA ( N=1425; response rate=67.31%). We
      limit analyses to respondents who received a vignette describing an individual
      meeting clinical criterion for schizophrenia or depression. Exploratory data
      analyses are used to examine overall patterns and cross-national differences.
      RESULTS: Graphical analyses show patterned similarities, especially for more
      individuals endorsing social distance as contact becomes more intimate. However,
      results also corroborate cross-national differences documented in media research.
      More Americans endorse evaluations of dangerousness, to both self and others.
      Fewer Icelanders report exclusionary tendencies, whilst Germans report the most
      consistently moderate levels of stigma. CONCLUSIONS: While Western nations tend
      to report similar, lower levels of stigma globally, they each have unique areas
      of concern. Anti-stigma programs must take note of both similarities and
      differences to tailor their efforts to the local context.

PMID- 29600745
TI  - Consult, Negotiate, and Involve: Evaluation of an Advanced Communication Skills
      Program for Health Care Professionals.
AB  - Effective communication is central to children, young people, and their families'
      experiences of health care. Most patient complaints in developed health care
      systems result from ineffective communication, including inadequate information
      provision, not feeling listened to, failure to value patients concerns, and
      patients not feeling involved in care decisions. Advanced communication skills
      training is now embedded within cancer care policy in the United Kingdom and now
      features prominently within cancer education in many countries. Here, we share
      findings from a research evaluation of an advanced communication skills training
      program dedicated to health professionals caring for children and young people
      with cancer. We evaluated participants' (n = 59) perceptions of the program,
      impact on their skills, knowledge, competence, and confidence. An appreciative
      inquiry design was adopted; data included interviews, precourse-postcourse
      evaluations, e-mail blog survey, and 360-degree reflective work records. The
      framework approach underpinned data analysis and triangulation of data sets. Key
      findings highlighted good and poor practice in health professionals' engagement
      with children, young people, and their families; the purpose of communicating
      effectively was not always consistent with collaborative working. Attending a
      program helped participants expand their knowledge of communication theories and
      strategies. Participants valued using simulated scenarios to develop their skills
      and were keen to use their new skills to enhance care delivery. Our emphasis
      within this evaluation, however, remained on what was communicated, when and how,
      rather than to what effect. The impact of programs such as these must now be
      evaluated in terms of patient benefit.

PMID- 29600746
TI  - "Hopefully This Will All Make Sense at Some Point": Meaning and Performance in
      Illness Blogs.
AB  - AIMS: To analyze the narratives of illness blogs created by parents of children
      with cancer. BACKGROUND: The profound effects of the childhood cancer experience
      on family members and the turn to the Internet by parents for help in the process
      are gaining research attention. DESIGN: The qualitative study design involved
      secondary narrative analysis of 14 illness blogs: 9 by the parents of children
      with neuroblastoma and 5 by the parents of children with leukemia. Daily blog
      entries were analyzed as individual units of illness experience expression and in
      relation to one another to identify thematic and linguistic similarities.
      METHODS: The initial analysis of these illness blogs resulted in identification
      of the quest for balance as a primary theme. Narratives in parents' childhood
      cancer illness blogs illustrated themes of performance. During this initial
      analysis, however, the author repeatedly asked, "Why are they writing this? And
      why publish this?" A second analysis of the data answered these questions of why
      parents blog about the experience. RESULTS: Narrative analysis resulted in the
      discovery of 6 main reasons that parents wrote and published the childhood cancer
      experience online: to report, explain, express, reflect, archive, and advocate.
      CONCLUSION: The analysis suggests that incorporation of parent writing may
      improve family--provider communication, enhance the family-health care
      professional relationship, enhance safety by preventing medical errors, improve
      reporting of clinical trial data such as adverse events, and improve
      satisfaction.

PMID- 29600747
TI  - The Effectiveness of a Hospital-Based School Liaison Program: A Comparative Study
      of Parental Perception of School Supports for Children With Pediatric Cancer and
      Neurofibromatosis Type 1.
AB  - Childhood survivors of central nervous system (CNS) cancers (defined as cancers
      whose diagnosis or treatment affect the CNS) are at increased risk for
      educational related difficulties, as are children affected by neurofibromatosis
      type 1. This study evaluated the effectiveness of and satisfaction with a model
      of psychoeducation, consultation, and advocacy provided by a School Liaison
      Program (SLP) for families and schools of children with CNS-involved cancers
      compared with a control group of parents of children with a diagnosis of
      neurofibromatosis type 1 who did not receive school-based services. Results
      indicated significant between-group differences in parents' belief that their
      child is meeting academic potential, with parents who received SLP services
      reporting greater satisfaction with their child's progress, better understanding
      of their child's learning needs, and an increased ability to access school
      supports. The strong, positive impact associated with the consultation,
      psychoeducation, and parental advocacy training provided by the SLP suggests that
      a similar model of care would potentially benefit other groups of children whose
      neurocognitive functioning is compromised by chronic medical conditions.

PMID- 29600749
TI  - Pigments from Filamentous Ascomycetes for Combination Therapy.
AB  - Filamentous ascomycetes (Neurospora and Monascus) have been studied for a long
      time because of their production of secondary metabolites such as microbial
      pigments. The ascomycetes represent an interesting group of compounds with high
      potential for medicinal applications. Many recent studies have shown their
      efficacy in the treatment of serious pathological states such as oncological
      diseases, neurodegenerative diseases and hyperlipidaemia. Nevertheless, the
      clinical usability of ascomycetes is still limited. However, this problem can be
      solved by use of these compounds with combinations of other therapeutic agents.
      This strategy can supress their side effects and improve their therapeutic
      efficiency. Moreover, their co-application can significantly enhance conventional
      therapies that are used. This review summarizes and discusses the general
      principles of this approach, introduced and supported by numerous examples. In
      addition, the prediction of the future potential application of this methodology
      is included.

PMID- 29600750
TI  - Terpenes, Phenylpropanoids, Sulfur and Other Essential Oil Constituents as
      Inhibitors of Cholinesterases.
AB  - Essential oils constituents are a diverse family of low molecular weight organic
      compounds with comprehensive biological activity. According to their chemical
      structure these active compounds can be divided into four major groups: terpenes,
      terpenoids, phenylpropenes, and "others". In addition, they may contain diverse
      functional groups according to which they can be classified as hydrocarbons
      (monoterpenes, sesquiterpenes, and aliphatic hydrocarbons); oxygenated compounds
      (monoterpene and sesquiterpene alcohols, aldehydes, ketones, esters, and other
      oxygenated compounds); and sulfur and/or nitrogen sulfur-containing compounds
      (thioesters, sulfides, isothiocyantes, nitriles, and others). Compounds that act
      as cholinesterase inhibitors still represent the only pharmacological treatment
      of Alzheimer's disease. Numerous in vitro studies showed that some compounds,
      found in essential oils, have a promising cholinesterase inhibitory activity,
      such as alpha-pinene, delta-3-carene, 1,8-cineole, carvacrol, thymohydroquinone,
      alpha- and beta-asarone, anethole, etc. This review summarizes the most relevant
      research published to date on essential oil constituents and their
      acetylcholinesterase/butyrylcholinesterase inhibitory potential as well as their
      structure related activity, synergistic and antagonistic effects.

PMID- 29600751
TI  - Electronegative LDL: an Active Player in Atherogenesis or a By-Product of
      Atherosclerosis?
AB  - Low-density lipoproteins (LDLs) are the major plasma carriers of cholesterol.
      However, LDL particles must undergo various molecular modifications to promote
      the development of atherosclerotic lesions. Modified LDL can be generated by
      different mechanisms, but as a common trait, show an increased electronegative
      charge of the LDL particle. A subfraction of LDL with increased electronegative
      charge (LDL(-)), which can be isolated from blood, exhibits several pro
      atherogenic characteristics. LDL(-) is heterogeneous, due to its multiple origins
      but is strongly related to the development of atherosclerosis. Nevertheless, the
      implication of LDL(-) in a broad array of pathologic conditions is complex and in
      some cases anti-atherogenic LDL(-) properties have been reported. In fact,
      several molecular modifications generating LDL(-) have been widely studied, but
      it remains unknown as to whether these different mechanisms are specific or
      common to different pathological disorders. In this review, we attempt to address
      these issues examining the most recent findings on the biology of LDL(-) and
      discussing the relationship between this LDL subfraction and the development of
      different diseases with increased cardiovascular risk. Finally, the review
      highlights the importance of minor apolipoproteins associated with LDL(-) which
      would play a crucial role in the different properties displayed by these modified
      LDL particles.

PMID- 29600752
TI  - Recent advances of mTOR inhibitors use in autosomal dominant polycystic kidney
      disease: is the road still open?
AB  - Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic
      kidney disease, is caused by mutations in the PKD1, PKD2 or, in a very limited
      number of families, GANAB genes. Although cellular and molecular mechanisms of
      this disease have been understood in the past 20 years, specific therapy
      approaches remain very little. Both experimental and clinical studies show that
      the mammalian or mechanistic target of rapamycin (mTOR) pathway plays an
      important role during cyst formation and enlargement in ADPKD. Studies in rodent
      models of ADPKD showed that mTOR inhibitors had a significant and long-lasting
      decrease in kidney volume and amelioration in kidney function. In the past over
      ten years, researchers have been devoting continuously to test mTOR inhibitors
      efficacy and safety in both preclinical studies and clinical trials in patients
      with ADPKD. In this review, we will discuss the mTOR pathway thoroughly, mainly
      focus on current advances in understanding its role in ADPKD, especially the
      recent progress of mTOR inhibitors use in preclinical studies and clinical
      trials.

PMID- 29600753
TI  - Bacterial Transferase MraY, a Source of Inspiration towards New Antibiotics.
AB  - The bacterial resistance to antibiotics constitutes more than ever a severe
      public health problem. The enzymes involved in bacterial peptidoglycan
      biosynthesis are pertinent targets for developing new antibiotics, notably the
      MraY transferase that is not targeted by any marketed drug. Many research groups
      are currently working on the study or the inhibition of this enzyme. After a
      concise overview of the role, mechanism and inhibition of MraY, the structure
      activity relationships of 5'-triazole-containing aminoribosyluridine inhibitors
      we previously synthetized will be presented. The recently published MraY X-ray
      structures allowed us to achieve a molecular virtual high-throughput screening of
      commercial data bases and our in-house library resulting in the identification of
      promising compounds for the further development of new antibiotics.

PMID- 29600754
TI  - In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using
      SOS/umu Tests and High-content In vitro Micronucleus Tests.
AB  - BACKGROUND: More than 2,000 chemicals have been used in the tannery industry.
      Although some tannery chemicals have been reported to have harmful effects on
      both human health and the environment, only a few have been subjected to
      genotoxicity and cytotoxicity evaluations. OBJECTIVE: This study focused on
      cytotoxicity and genotoxicity of ten tannery chemicals widely used in China.
      MATERIALS AND METHODS: DNA-damaging effects were measured using the SOS/umu test
      with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic
      effects were determined with the high-content in vitro Micronucleus test (MN
      test) using the human-derived cell lines MGC-803 and A549. CONCLUSION: The
      cytotoxicity of the ten tannery chemicals differed somewhat between the two cell
      assays, with A549 cells being more sensitive than MGC-803 cells. None of the
      chemicals induced DNA damage before metabolism, but one was found to have DNA
      damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120,
      were found to have chromosome-damaging effects. A Quantitative Structure-Activity
      Relationship (QSAR) analysis indicated that one structural feature favouring
      chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the
      chromosome-damaging effects of the four MN-test-positive chemicals.

PMID- 29600755
TI  - Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors.
AB  - BACKGROUND: Infections caused by microorganisms are the major cause of death
      today. The tremendous and improper use of antimicrobial agents leads to
      antimicrobial resistance. AIM AND OBJECTIVE: Various currently available
      antimicrobial drugs are inadequate to control the infections and lead to various
      adverse drug reactions. Efforts based on computer-aided drug design (CADD) can
      excavate a large number of databases to generate new, potent hits and minimize
      the requirement of time as well as money for the discovery of newer
      antimicrobials. Pharmaceutical sciences also have made development with advances
      in drug designing concepts. The current research article focuses on the study of
      various G-6-P synthase inhibitors from literature cited molecular database.
      Docking analysis was conducted and ADMET data of various molecules was evaluated
      by Schrodinger Glide and PreADMET software, respectively. Here, the results
      presented efficacy of various inhibitors towards enzyme G-6-P synthase. Docking
      scores, binding energy and ADMET data of various molecules showed good inhibitory
      potential toward G-6-P synthase as compared to standard antibiotics. This novel
      antimicrobial drug target G-6-P synthase has not so extensively been explored for
      its application in antimicrobial therapy, so the work done so far proved highly
      essential. This article has helped the drug researchers and scientists to
      intensively explore about this wonderful antimicrobial drug target. MATERIALS AND
      METHODS: The Schrodinger, Inc. (New York, USA) software was utilized to carry out
      the computational calculations and docking studies. The hardware configuration
      was Intel(r) core (TM) i5-4210U CPU @ 2.40GHz, RAM memory 4.0 GB under 64-bit
      window operating system. The ADMET data was calculated by using the PreADMET tool
      (PreADMET ver. 2.0). All the computational work was completed in the Laboratory
      for Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D.
      University, Rohtak, INDIA. RESULTS: Molecular docking studies were carried out to
      identify the binding affinities and interaction between the inhibitors and the
      target proteins (G-6-P synthase) by using Glide software (Schrodinger Inc. U.S.A.
      Maestro version 10.2). Grid-based Ligand Docking with Energetic (Glide) is one of
      the most accurate docking softwares available for ligand-protein, protein-protein
      binding studies. A library of hundreds of available ligands was docked against
      targeted proteins G-6-P synthase having PDB ID 1moq. Results of docking are shown
      in Table 1 and Table 2. Results of G-6-P synthase docking showed that some
      compounds were found to have comparable docking score and binding energy (kj/mol)
      as compared to standard antibiotics. Many of the ligands showed hydrogen bond
      interaction, hydrophobic interactions, electrostatic interactions, ionic
      interactions and pi- pi stacking with the various amino acid residues in the
      binding pockets of G-6-P synthase. CONCLUSION: The docking study estimated free
      energy of binding, binding pose andglide score and all these parameters provide a
      promising tool for the discovery of new potent natural inhibitors of G-6-P
      synthase. These G-6-P synthase inhibitors could further be used as
      antimicrobials. Here, a detailed binding analysis and new insights of inhibitors
      from various classes of molecules were docked in binding cavity of G-6-P
      synthase. ADME and toxicity prediction of these compounds will further accentuate
      us to study these compounds in vivo. This information will possibly present
      further expansion of effective antimicrobials against several microbial
      infections.

PMID- 29600756
TI  - Potential pharmacokinetic herb-drug interactions: have we overlooked the
      importance of human carboxylesterases 1 and 2?
AB  - Herbal products have grown steadily across the globe over the past 10 years and
      have increasingly been incorporated into western medicine for healthcare aims,
      thereby causing potential pharmacokinetic herb-drug interactions (HDI) through
      the inhibition or induction of drug-metabolizing enzymes and transporters. Human
      carboxylesterases 1 (CES1) and 2 (CES2) are versatile enzymes involvement in the
      metabolism of endogenous and exogenous compounds including many important
      therapeutic medications. Moreover, the growing number of CES substrate drugs also
      underscores the importance of CES1 and CES2. Here, we summarized those potential
      inhibitors and inducers coming from herbal constituents towards CES1 and CES2. We
      also reviewed those published HDI studies focusing on herbal products and
      therapeutic agents metabolized by CES1 or CES2. Our results showed that more than
      50 natural inhibitors of CES1 or CES2 including phenolic chemicals,
      triterpenoids, and tanshinones were found from herbs, whereas inducers for both
      CES1 and CES2 are scarce. Systemic exposure to some commonly used drugs including
      oseltamivir, irinotecan, and clopidogrel were found to altered in animals when
      they were co-administered with herb products such as goldenseal, black cohosh,
      ginger, St John's Wort, curcumin, and Chinese compound formula. However, the HDI
      risk is likely to be low according to the very limited published data.
      Preclinical experimentation and clinical trials are warranted in the future to
      provide relevant safety data for the public especially for consumers and
      healthcare providers toward better clinical outcomes for herbal products and
      conventional drugs.

PMID- 29600757
TI  - Preclinical Hepatoprotective Effect of Herbalism Against Ethanol Induced
      Hepatotoxicity: A Review.
AB  - BACKGROUND: Liver ailments including alcoholic liver disease (ALD), still remain
      the main reason for morbidity & mortality worldwide. In fact, ALD is a
      multifactorial disease with complex pathophysiology which is linked to several
      types of liver damages including steatohepatitis, fibrosis and cirrhosis.
      METHODS: This review emphasizes on 30 herbal medicinal plants with their extracts
      studied for protective effect against ALD and current scientific evidence of ALD
      cure by thirty Indian Materia Medica including Tilia Platyphyllos, Amomum
      subulatum, Carica papaya, Pogostemon patchouli, Commelina benghalensis,
      Bacopamonnieri, Pecan nut, Allium cepa, Beta Vulgaris, Adina cordifolia, Ocimum
      gratissimum, Vernonia amygdalina, Sida veronicaefolia, Chenopodium album, Korean
      red ginseng, Elephantopus scaber, Tecomella undulata, Prunus armeniaca, Sea
      tangle (Laminaria japonica), Emblica officinalis, Saccharum officinarum, Cocculus
      hirsutus, Cassia roxburghii, Zhi-Zi-Da- Huang, Phyllanthus amarus, Aegle
      marmelos, Agrimonia eupatoria, Flaveria trinervia, Curcuma longa and Garcinia
      indica. RESULTS: Reduction in oxidative stress, improvement in inflammation,
      reduction in degeneration of fat and necrosis are some of the mechanisms of
      action of these medicinal plants observed in alcohol induced in-vivo and in-vitro
      liver injury models. CONCLUSION: Accordingly, this review provides several
      evidences which show that these medicinal plants could be used for the treatment
      and prevention of ALD.

PMID- 29600758
TI  - Indomethacin Analogs: Synthesis, Anti-inflammatory and Analgesic Activities of
      Indoline Derivatives.
AB  - BACKGROUND: Microwave assisted reactions offer a considerable advantages over
      conventional method reactions because the former results in substantial rate
      enhancement in a wide range of organic reactions. OBJECTIVE: we interested herein
      to prepare new anti-inflammatory and analgesic agents analogues to Indomethacin
      in short reaction time by using microwaves irradiation. METHOD: Synthesis of new
      hydrazonoindolines having thiazole moiety under microwave irradiation were
      achieved via the reaction of hydrazonoyl chlorides or halogenated active
      methylene derivatives with thiosemicarbazone derivatives. Also, the utility of
      the versatile indoline-2,3-dione derivatives in the design of new multifunctional
      building blocks using condensation with hydrazine derivatives was demonstrated.
      RESULTS: All products were formed in short reaction time and high yield. The
      information derived from the spectral data of the formed compounds was confirmed
      their structures. Also, the analgesic and antiinflammatory activities of the
      designed derivatives were screened and the results obtained indicated that six
      derivatives 4g, 9b, 4c, 10b, 4d and 11a revealed the highest anti-inflammatory
      and analgesic effects. CONCLUSION: we succeeded in this context to design and
      synthesis of new anti-inflammatory and analgesic agents analogues to Indomethacin
      in short reaction time and with high yield.

PMID- 29600759
TI  - Indandione and Its Derivatives - Chemical Compounds with High Biological
      Potential.
AB  - Indandione is a hydrocarbon classified as bicyclic aromatic beta-diketone. It can
      be applied in many fields of science and industry. It is successfully used as a
      substrate in organic synthesis, pharmaceutical sciences and as a substrate for
      the production of dyes. Indandione derivatives and analogs are useful in
      medicine, chemistry and the judiciary. Among the indandione derivatives can find
      compounds that have interesting properties and many of them have biological
      activity (incl. anticancer, anticoagulation, anti-inflamatory, antimicrobial
      activities). Based on the indan-1,3-dione structure created acetylcholinesterase
      inhibitors. Indan-1,3-dione derivatives are also used as a derivating agent for
      the analysis of fatty aldehydes and a substance that is an element of dye
      sensitized solar cells. This work presents a brief overview of construction,
      properties and activities of indandione and its derivatives. This work describes
      selected indandione derivatives that have properties useful in medicine and
      industry with particular regard to the anticoagulants and neuroprotective
      activities in AD.

PMID- 29600760
TI  - Ultrasound Assisted Cu-catalyzed Synthesis of 1,2-Disubstituted Benzimidazoles as
      Potential Antibacterial Agents.
AB  - BACKGROUND: The ultrasound assisted synthesis and anti-bacterial evaluation of a
      series of compounds based on 1,2-disubstituted benzimidazole framework is
      reported here. The approach leading to the synthesis of these compounds involved
      the Cu-catalyzed coupling-cyclization of N-substituted 2-iodoanilines with
      benzamide derivatives in the presence of 2-aminoethanol as a ligand. CONCLUSION:
      A number of compounds were prepared using this methodology in acceptable yield.
      Two of these compounds showed promising antibacterial activities when tested
      against both Gram-positive and Gram-negative bacterial strains.

PMID- 29600761
TI  - Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial
      Agents: Synthesis and QSAR Analysis.
AB  - New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in
      vitro evaluated for their antiproliferative activity against three human cancer
      cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate
      adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency
      was elicited by the target candidates against the viability of HCT116 cell lines,
      higher than the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 uM, IC50,
      5-FU; 1.10 uM). Cell cycle analysis and apoptosis activation revealed that
      compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition,
      20 activates the caspases-9 and -3, a process which might mediate the apoptosis
      of HCT116 cells. Quantitative structure activity relationship study was done and
      revealed a high predictive power R2 suggesting goodness of the models.
      Furthermore, there is a good agreement between the observed pIC50 and the
      predicted pIC50 values, in addition, the low RMSD and standard error values
      indicate the accuracy of the model. Antimicrobial evaluation revealed that some
      of these compounds exhibited significant activities against the tested pathogenic
      bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent
      and broad spectrum antibacterial and antifungal potency equivalent to that
      revealed by Vibramycin and Ketoconazole (MIC; 125 MUg/mL). Moreover, compounds
      15a, 21c, investigated dual potent antimicrobial and anticancer activity.

PMID- 29600762
TI  - Prodrugs of Non-steroidal Anti-inflammatory Drugs (NSAIDs): A Long March Towards
      Synthesis of Safer NSAIDs.
AB  - As a therapeutic group, non-steroidal anti-inflammatory drugs (NSAIDs) are among
      the most widely used, prescribed and over the counter (OTC) medications for the
      treatment of inflammatory diseases, but suffering from several undesired side
      effects, the most important being ulcerogenicity, mucosal hemorrhage and
      gastritis. Most of the NSAID moieties are chemically composed of carboxylic
      functional groups and this could be one of the reasons for the damage to the
      mucosal lining. The prodrug designing is one of the several strategies used to
      overcome this drawback. Hence, in the last decade, the design and the synthesis
      of prodrugs of NSAIDs have been explored and given much attention by medicinal
      chemists. The rationale behind the prodrug concept is to achieve temporary
      blockade of the free carboxylic group present in the NSAIDs till their systemic
      absorption. This review is aimed to highlight and provide important information
      on NSAID prodrugs that have been designed and reported to be safe and more
      effective. This review will also focus on NSAID prodrugs that have been designed
      for improving therapeutic i.e. anti-inflammatory action as well as improving drug
      delivery at the target site. The most common derivatives of carboxylic NSAIDs
      that are discussed here belong to the chemical classes of esters, amides,
      anhydrides, acetals and the other derivatives with completely masked carboxylic
      groups. The successful prodrugs were listed and their molecular structures were
      also demonstrated here. The present review covers the recent updates present in
      literature and will surely provide a greater insight into the designing of safer
      NSAIDs in the future.

PMID- 29600763
TI  - Ryanodine Receptors for Drugs and Insecticides: An Overview.
AB  - Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic
      reticulum of muscle cells and neurons. They regulate release of stored
      intracellular calcium and play a critical role in muscle contraction. The N
      terminal part of these receptors accounts for roughly 80% and contains the
      binding sites for diverse RyRs modulators. The C-terminal domain contains the
      transmembrane region. Ryanodine, a plant alkaloid, has been investigated
      extensively as a potential pest control agent but no selectivity between
      mammalians and insect pests. The diamides (e.g., flubendiamide, cyantraniliprole
      and chlorantraniliprole) are the main commercial insecticides targeting insect
      RyRs. Due to the excessive application, amino acid mutations led to insect
      resistance to diamides. Furthermore, microRNA (miR-7a and miR-8519) could
      regulate overexpression of RyRs involved in chlorantraniliprole resistance, and
      lncRNAs are also associated with chlorantraniliprole resistance in Plutella
      xylostella. This review summarizes the current knowledge about the insect RyRs,
      their antagonists and activators, and the resistance mechanisms (including amino
      acid mutations, metabolic, genetic and fitness costs resistances, and miRNA and
      lncRNA in diamides resistances). This may lay the foundation for effective
      management of diamides resistances.

PMID- 29600764
TI  - Probing Gallic Acid for Its Broad Spectrum Applications.
AB  - Gallic acid and its derivatives not only exhibit excellent antioxidant,
      anticarcinogenic, antimutagenic, antimicrobial properties but also provide
      protection to the cells against oxidative stress. Gallic acid (3, 4, 5
      trihydroxybenzoic acid), a low molecular triphenolic compound emerged as an
      efficient apoptosis inducing agent. The antimicrobial and other biological
      properties of gallic acid and its derivatives seemed to be linked with the
      hydrolysis of ester linkage between gallic acid and polyols like tannins
      hydrolyzed after ripening of many edible fruits. Gallic acid serves a natural
      defense mechanism against microbial infections and modulation of immune
      responses. The current review updates us with the diverse roles played by gallic
      acid, its antioxidant potential, action mechanism and more importantly the
      diverse array of applications in therapeutic and pharmaceutical areas.

PMID- 29600765
TI  - Network Pharmacology: Exploring the Resources and Methodologies.
AB  - Multi-target and combinatorial therapies have been focused for the past several
      decades. These approaches achieved considerable therapeutic efficacy by
      modulating the activities of the targets in complex diseases such as HIV-1
      infection, cancer and diabetes disease. Most of the diseases cannot be treated
      efficiently in terms of single gene target, because it involves the cessation of
      the coordinated function of distinct gene groups. Most of the cellular components
      work efficiently by interacting with other cellular components and all these
      interactions together represent interactome. This interconnectivity shows that a
      defect in a single gene may not be restricted to the gene product itself, but may
      spread along the network. So, drug development must be based on the network-based
      perspective of disease mechanisms. Many systematic diseases like
      neurodegenerative disorders, cancer and cardiovascular cannot be treated
      efficiently by the single gene target strategy because these diseases involve the
      complex biological machinery. In clinical trials, many mono-therapies have been
      found to be less effective. In mono-therapies, the long term treatment, for the
      systematic diseases make the diseases able to acquired resistance because of the
      disease nature of the natural evolution of feedback loop and pathway redundancy.
      Multi-target drugs might be more efficient. Multi-target therapeutics might be
      less vulnerable because of the inability of the biological system to resist
      multiple actions. In this study, we will overview the recent advances in the
      development of methodologies for the identification of drug target interaction
      and its application in the poly-pharmacology profile of the drug.

PMID- 29600766
TI  - Discovering Synergistic Drug Combination from a Computational Perspective.
AB  - Synergistic drug combinations play an important role in the treatment of complex
      diseases. The identification of effective drug combination is vital to further
      reduce the side effects and improve therapeutic efficiency. In previous years, in
      vitro method has been the main route to discover synergistic drug combinations.
      However, many limitations of time and resource consumption lie within the in
      vitro method. Therefore, with the rapid development of computational models and
      the explosive growth of large and phenotypic data, computational methods for
      discovering synergistic drug combinations are an efficient and promising tool and
      contribute to precision medicine. It is the key of computational methods how to
      construct the computational model. Different computational strategies generate
      different performance. In this review, the recent advancements in computational
      methods for predicting effective drug combination are concluded from multiple
      aspects. First, various datasets utilized to discover synergistic drug
      combinations are summarized. Second, we discussed feature-based approaches and
      partitioned these methods into two classes including feature-based methods in
      terms of similarity measure, and feature-based methods in terms of machine
      learning. Third, we discussed network-based approaches for uncovering synergistic
      drug combinations. Finally, we analyzed and prospected computational methods for
      predicting effective drug combinations.

PMID- 29600767
TI  - Identification and Characterization of Positively Selected Mutations in Nef of
      Four HIV-1 Major Subtypes from Los Alamos National Laboratory.
AB  - BACKGROUND: Human immunodeficiency virus-1 (HIV-1) mutates rapidly to escape host
      immune pressure. This results in the generation of positively selected mutations
      (PSM) throughout the viral genome. Escape mutations in Nef, one of the accessory
      proteins of HIV-1, which plays an important role in viral pathogenicity have
      previously been identified in several large cohort studies, but the evolution of
      PSMs overtime in various HIV-1 subtypes remains unknown. METHODS: 161 clade A1,
      3093 clade B, 647 clade C and 115 clade D HIV-1 nef sequences were obtained from
      the HIV Database of Los Alamos National Laboratory and aligned using MEGA 6.0.
      The sequences from each clade were grouped based on the year of collection. Quasi
      analysis was used to identify PSMs and the number and locations of PSMs were
      compared among different subtypes. RESULTS: PSMs for all four subtypes were
      distributed across the sequence of Nef, and conserved residues F90, W113, PxxPxR
      (a.a 72-77) remain unaltered overtime. The frequency of PSMs was stable among
      subtype B sequences but increased overtime for other subtypes. Phylogenetic
      analysis shows that sequences containing PSMs tend to cluster together at both
      inter and intra- subtype levels. CONCLUSION: Identification of PSMs and their
      changes overtime within various subtypes of HIV-1 is important in defining global
      viral evolutionary patterns that can provide insights for designing therapeutic
      strategies.

PMID- 29600768
TI  - The hepato-protective effects of Portulaca oleracea L. extract: review.
AB  - Portulaca oleracea L. (Purslane) has been used in traditional medicine against
      hepatic injury, alt-hough its actual efficacy has not been fully understood. In
      addition, few studies have indicated that Portulaca oleracea L. possess
      protective effects against hepatotoxic agents. However, due to lack of
      information in human, more studies are needed to confirm the efficacy of
      Portulaca oleracea L. as a hepato-protective agent. The present study aimed to
      critically review the recent literature data from 1990 to 2017 regarding the
      hepato-protective effects of Portulaca oleracea L. and its underlying mechanisms.

PMID- 29600770
TI  - Antimicrobial Resistance: a One Health Perspective.
AB  - One Health is the collaborative effort of multiple health science professions to
      attain optimal health for people, domestic animals, wildlife, plants, and our
      environment. The drivers of antimicrobial resistance include antimicrobial use
      and abuse in human, animal, and environmental sectors and the spread of resistant
      bacteria and resistance determinants within and between these sectors and around
      the globe. Most of the classes of antimicrobials used to treat bacterial
      infections in humans are also used in animals. Given the important and
      interdependent human, animal, and environmental dimensions of antimicrobial
      resistance, it is logical to take a One Health approach when addressing this
      problem. This includes taking steps to preserve the continued effectiveness of
      existing antimicrobials by eliminating their inappropriate use and by limiting
      the spread of infection. Major concerns in the animal health and agriculture
      sectors are mass medication of animals with antimicrobials that are critically
      important for humans, such as third-generation cephalosporins and
      fluoroquinolones, and the long-term, in-feed use of medically important
      antimicrobials, such as colistin, tetracyclines, and macrolides, for growth
      promotion. In the human sector it is essential to prevent infections, reduce over
      prescribing of antimicrobials, improve sanitation, and improve hygiene and
      infection control. Pollution from inadequate treatment of industrial,
      residential, and farm waste is expanding the resistome in the environment.
      Numerous countries and several international agencies have included a One Health
      approach within their action plans to address antimicrobial resistance. Necessary
      actions include improvements in antimicrobial use regulation and policy,
      surveillance, stewardship, infection control, sanitation, animal husbandry, and
      alternatives to antimicrobials. WHO recently has launched new guidelines on the
      use of medically important antimicrobials in food-producing animals, recommending
      that farmers and the food industry stop using antimicrobials routinely to promote
      growth and prevent disease in healthy animals. These guidelines aim to help
      preserve the effectiveness of antimicrobials that are important for human
      medicine by reducing their use in animals.

PMID- 29600769
TI  - Anti-Cancer Effect of alpha-Solanine by Down-Regulating S100P Expression in
      Colorectal Cancer Cells.
AB  - BACKGROUND: alpha-Solanine, the most important and active component of Solanum
      nigrum, was found to have anti-cancer activity on multiple cancer cells. However,
      its effects on colorectal cancer (CRC) and associated molecular mechanisms remain
      to be further elucidated. OBJECTIVE: In this study, we investigated the anti
      cancer effects of alpha-solanine against CRC cells in vitro and in vivo.
      MATERIALS & METHODS: Cell viability was measured using Cell Counting Kit-8 (CCK
      8) assay; cell cycle was analyzed with a Cycletest Plus DNA Reagent Kit; cell
      apoptosis was detected by flow cytometer; cell migration and invasive ability was
      determined by Transwell assays; S100P protein expression was also analyzed by
      western blotting; lentiviral vectors expressing shRNA targeting the S100P gene.
      RESULTS: We demonstrated that alpha-solanine inhibited CRC cell (SW480, SW620 and
      HT-29) growth as well as migration and invasion, induced cell cycle arrest and
      apoptosis in vitro, and suppressed tumor growth in vivo. Moreover, we observed
      that S100P expression was downregulated by alpha-solanine. Overexpression of
      S100P partially reversed the alpha-solanine-induced growth inhibition of CRC
      cells. Conversely, knockdown of S100P by lentiviral-mediated RNAi resulted in
      significantly promoting the alpha-solanine-induced growth inhibition. CONCLUSION:
      These findings suggest that alpha-solanine is a potential agent for the treatment
      of CRC, and the anti-tumor effect of alpha-solanine in the CRC cells may be
      mediated at least partly by the downregulation of S100P.

PMID- 29600771
TI  - Antimicrobial Susceptibility Testing of Bacteria of Veterinary Origin.
AB  - Antimicrobial susceptibility testing is an essential tool to the veterinarian for
      selecting the most appropriate agent for treatment of bacterial diseases of
      animals. The availability of well-defined methods that incorporate the necessary
      quality controls coupled to clinical outcome data is foundational in providing
      relevant test results for clinical decisions. Since 1993, the Clinical Laboratory
      and Standards Institute (CLSI) Subcommittee on Veterinary Antimicrobial
      Susceptibility Testing (VAST) has developed specific test methods and
      interpretive criteria for veterinary pathogens. This information has allowed for
      veterinarians to more effectively treat animal diseases thereby protecting both
      animal welfare and human food security. Moreover, the availability of
      standardized test methods for veterinary pathogens has allowed for the
      development of antimicrobial surveillance programs to detect the emergence of
      resistance among veterinary pathogens. Future work by the VAST and other groups
      will be critical to expanding the current test methods and interpretive criteria
      to more pathogen-antibacterial combinations, as well as, the incorporation of
      genomic information for routine antimicrobial susceptibility testing in the
      veterinary diagnostic laboratory.

PMID- 29600772
TI  - Antimicrobial Resistance in Streptococcus spp.
AB  - The genus Streptococcus includes Gram-positive organisms shaped in cocci and
      organized in chains. They are commensals, pathogens, and opportunistic pathogens
      for humans and animals. Most Streptococcus species of veterinary relevance have a
      specific ecological niche, such as S. uberis, which is almost exclusively an
      environmental pathogen causing bovine mastitis. In contrast, S. suis can be
      considered as a true zoonotic pathogen, causing specific diseases in humans after
      contact with infected animals or derived food products. Finally, Streptococcus
      species such as S. agalactiae can be sporadically zoonotic, even though they are
      pathogens of both humans and animals independently. For clarification, a short
      taxonomical overview will be given here to highlight the diversity of
      streptococci that infect animals. Several families of antibiotics are used to
      treat animals for streptococcal infections. First-line treatments are penicillins
      (alone or in combination with aminoglycosides), macrolides and lincosamides,
      fluoroquinolones, and tetracyclines. Because of the selecting role of
      antibiotics, resistance phenotypes have been reported in streptococci isolated
      from animals worldwide. Globally, the dynamic of resistance acquisition in
      streptococci is slower than what is experienced in Enterobacteriaceae, probably
      due to the much more limited horizontal spread of resistance genes. Nonetheless,
      transposons or integrative and conjugative elements can disseminate resistance
      determinants among streptococci. Besides providing key elements on the prevalence
      of resistance in streptococci from animals, this article will also largely
      consider the mechanisms and molecular epidemiology of the major types of
      resistance to antimicrobials encountered in the most important streptococcal
      species in veterinary medicine.

PMID- 29600774
TI  - Atrial Fibrillation Ablation: Simplicity Is the Answer.

PMID- 29600773
TI  - Source-Sink Mismatch Causing Functional Conduction Block in Re-Entrant
      Ventricular Tachycardia.
AB  - Ventricular tachycardia (VT) caused by a re-entrant circuit is a life-threatening
      arrhythmia that at present cannot always be treated adequately. A realistic model
      of re-entry would be helpful to accurately guide catheter ablation for
      interruption of the circuit. In this review, models of electrical activation
      wavefront propagation during onset and maintenance of re-entrant VT are
      discussed. In particular, the relationship between activation mapping and maps of
      transition in infarct border zone thickness, which results in source-sink
      mismatch, is considered in detail and supplemented with additional data. Based on
      source-sink mismatch, the re-entry isthmus can be modeled from its boundary
      properties. Isthmus boundary segments with large transitions in infarct border
      zone thickness have large source-sink mismatch, and functional block forms there
      during VT. These alternate with segments having lesser thickness change and
      therefore lesser source-sink mismatch, which act as gaps, or entrance and exit
      points, to the isthmus during VT. Besides post-infarction substrates, the source
      sink model is likely applicable to other types of volumetric changes in the
      myocardial conducting medium, such as when there is presence of fibrosis or
      dissociation of muscle fibers.

PMID- 29600775
TI  - Left Atrial Appendage Electrical Isolation for Treatment of Recurrent Atrial
      Fibrillation: A Meta-Analysis.
AB  - OBJECTIVES: In this study, the authors sought to perform a meta-analysis of
      controlled studies assessing the relationship between left atrial appendage (LAA)
      electrical isolation (EI) and recurrent atrial fibrillation (AF). BACKGROUND: LAA
      triggers could play an important role in AF and can be treated with complete EI
      of the LAA via surgical or percutaneous approaches. METHODS: We conducted a meta
      analysis of all controlled studies published as of November 21, 2016, assessing
      the relationship between left atrial appendage electrical isolation (LAAEI) and
      recurrent AF. The primary endpoint was atrial tachycardia (AT) or AF recurrence
      after the post-procedure blanking period. The association between LAAEI and AT/AF
      was estimated using random-effects modeling. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated using the DerSimonian and Laird
      method. RESULTS: We identified 7 studies including 1,037 patients; LAAEI was
      performed in 566 patients (55%). LAAEI was associated with a significantly lower
      rate of AT/AF recurrence in the primary analysis (OR: 0.38; 95% CI: 0.16 to 0.90;
      p = 0.02). The association between LAAEI and recurrent AT/AF was strongest in a
      sensitivity analysis restricted to studies of percutaneous LAAEI (OR: 0.22; 95%
      CI: 0.11 to 0.46; p < 0.001; 5 studies, n = 623). LAAEI was not associated with
      thromboembolism (OR: 0.50; 95% CI: 0.18 to 1.39; p = 0.18; 5 studies, n = 767),
      although these studies either incorporated LAA occlusion (3 studies, n = 552
      patients) or follow-up echocardiography to assess LAA function (2 studies, n =
      215 patients) to inform antithrombotic strategies. CONCLUSIONS: LAAEI is
      associated with a significant reduction in recurrent AT/AF. Randomized trials are
      required to confirm the efficacy and long-term safety of LAAEI and to determine
      the optimal concomitant antithrombotic strategy.

PMID- 29600776
TI  - Left Atrial Appendage Electric Isolation for Treatment of Atrial Fibrillation:
      Experimental Approach or Standard of Care?

PMID- 29600777
TI  - Rotor Mapping in Atrial Fibrillation: Driven to Distraction?

PMID- 29600778
TI  - Integrated Assessment of Left Ventricular Electrical Activation and Myocardial
      Strain Mapping in Heart Failure Patients: A Holistic Diagnostic Approach for
      Endocardial Cardiac Resynchronization Therapy, Ablation of Ventricular
      Tachycardia, and Biological Therapy.
AB  - OBJECTIVES: This study sought to test the accuracy of strain measurements based
      on anatomo-electromechanical mapping (AEMM) measurements compared with magnetic
      resonance imaging (MRI) tagging, to evaluate the diagnostic value of AEMM-based
      strain measurements in the assessment of myocardial viability, and the additional
      value of AEMM over peak-to-peak local voltages. BACKGROUND: The in vivo
      identification of viable tissue, evaluation of mechanical contraction, and
      simultaneous left ventricular activation is currently achieved using multiple
      complementary techniques. METHODS: In 33 patients, AEMM maps (NOGA XP, Biologic
      Delivery Systems, Division of Biosense Webster, a Johnson & Johnson Company,
      Irwindale, California) and MRI images (Siemens 3T, Siemens Healthcare, Erlangen,
      Germany) were obtained within 1 month. MRI tagging was used to determine
      circumferential strain (Ecc) and delayed enhancement to obtain local scar extent
      (%). Custom software was used to measure Ecc and local area strain (LAS) from the
      motion field of the AEMM catheter tip. RESULTS: Intertechnique agreement for Ecc
      was good (R2 = 0.80), with nonsignificant bias (0.01 strain units) and narrow
      limits of agreement (-0.03 to 0.06). Scar segments showed lower absolute strain
      amplitudes compared with nonscar segments: Ecc (median [first to third quartile]:
      nonscar -0.10 [-0.15 to -0.06] vs. scar -0.04 [-0.06 to -0.02]) and LAS (-0.20 [
      0.27 to -0.14] vs. -0.09 [-0.14 to -0.06]). AEMM strains accurately discriminated
      between scar and nonscar segments, in particular LAS (area under the curve: 0.84,
      accuracy = 0.76), which was superior to peak-to-peak voltages (nonscar 9.5 [6.5
      to 13.3] mV vs. scar 5.6 [3.4 to 8.3] mV; area under the curve: 0.75).
      Combination of LAS and peak-to-peak voltages resulted in 86% accuracy.
      CONCLUSIONS: An integrated AEMM approach can accurately determine local
      deformation and correlates with the scar extent. This approach has potential
      immediate application in the diagnosis, delivery of intracardiac therapies, and
      their intraprocedural evaluation.

PMID- 29600779
TI  - Internal Jugular Venous Approach to Percutaneous Vacuum-Assisted Debulking of
      Large Lead Vegetations Prior to Lead Extraction.

PMID- 29600780
TI  - Cardiovascular Magnetic Resonance Imaging in a Patient With Implanted Leadless
      Pacemaker.

PMID- 29600781
TI  - Escape Mapping: Rapid Identification of Pulmonary Vein Isolation Gaps Utilizing
      an Ablation Catheter.

PMID- 29600782
TI  - Impact of Atrial Fibrillation on Natriuretic Peptides: An Invasive Atrial
      Hemodynamic Study.

PMID- 29600783
TI  - A Secret Marriage Between Fibrosis and Atrial Fibrillation Drivers.

PMID- 29600784
TI  - Useful Electrocardiographic Features to Help Identify the Mechanism of Atrial
      Tachycardia Occurring After Persistent Atrial Fibrillation Ablation.
AB  - OBJECTIVES: The purpose of this study was to describe and identify useful
      electrocardiographic characteristics to help identify the mechanism of atrial
      tachycardia (AT) occurring after persistent atrial fibrillation (PsAF) ablation.
      BACKGROUND: Electrocardiographic analysis to help identify the mechanism of AT
      after PsAF ablation is much limited by the fact that remodeling and ablation
      alter the normal activation pattern. METHODS: All consecutive patients who
      underwent mapping and ablation of AT after PsAF ablation were included. Surface P
      waves were analyzed during higher (>2:1) grades of atrioventricular block.
      RESULTS: One hundred ninety-six ATs with visible P waves were identified in 127
      patients (macro-re-entry in 57%, centrifugal AT in 43%). One-third displayed low
      voltage P waves (<=0.1 mV). An isoelectric line >80 ms was more common in
      centrifugal compared with macro-re-entrant AT (47% vs. 24%; p < 0.001), but its
      positive predictive value was limited (60%). A minority of peritricuspid ATs
      displayed the classic saw-tooth pattern (27% [n = 22]). However, the "precordial
      transition" (a gradual transition from an upright component in lead V1 to a
      negative component with progression across the precordium) remained often
      observed and specifically identified peritricuspid AT (specificity, 98%;
      sensitivity, 59%). Only 2 unique features could help identify perimitral AT (n =
      60). First, the presence of a negative or negative-positive P-wave in any of
      leads V2 to V6 identified perimitral AT with 97% specificity and 30% sensitivity.
      Second, a "notched" negative component at the beginning of a positive P-wave in
      the inferior leads specifically identified clockwise perimitral AT (specificity,
      98%; sensitivity, 25%). CONCLUSIONS: Only few unique electrocardiographic
      characteristics help identify the mechanism of AT after PsAF ablation. Knowledge
      of these characteristics may aid in planning and performing ablation.

PMID- 29600785
TI  - Utility of the Electrocardiogram in Mapping of Atrial Tachycardia Post-Atrial
      Fibrillation Ablation: Back to the Basics.

PMID- 29600786
TI  - The Spatial Distribution of Late Gadolinium Enhancement of Left Atrial Magnetic
      Resonance Imaging in Patients With Atrial Fibrillation.
AB  - OBJECTIVES: The purpose of this study is to evaluate the spatial distribution of
      late gadolinium enhancement (LGE) of the left atrium (LA) by LGE-magnetic
      resonance imaging in an atrial fibrillation (AF) population. BACKGROUND: LGE of
      the LA can be a surrogate of pre-existing structural remodeling of LA. METHODS:
      LGE-magnetic resonance imaging scans were used for 160 patients with AF (mean age
      66 +/- 11 years) before AF ablation. To know the spatial distribution of LGE, the
      extent of LGE in 6 LA subregions was examined. Overall LGE distribution was also
      summarized as a spatial frequency histogram using an atlas of LA shape. These
      data were also compared between paroxysmal AF (87 patients) and persistent AF (73
      patients). RESULTS: LGE coverage (%) in each subregion was as follows: 41.8 +/-
      18.9% in the left pulmonary vein (PV) antrum, 27.1 +/- 16.7% in the left lateral
      wall, 25.8 +/- 15.3% in the posterior wall, 19.7 +/- 15.3% in the anterior wall,
      17.1 +/- 15.0% in the right PV antrum, and 12.0 +/- 13.2% in the septum wall. LGE
      was heterogeneously distributed in the LA and was found with the highest
      frequency in the posterior wall near the inferior left PV antrum by the LGE
      histogram. A comparison of paroxysmal AF with persistent AF suggests that LGE was
      more expected in persistent AF compared with paroxysmal AF, particularly with a
      spread on the posterior and the anterior wall. CONCLUSIONS: LGE in the LA was
      heterogeneously distributed. LGE was highly distributed in the inferior left PV
      antrum near the posterior wall side, and spread on the posterior and anterior
      wall with AF progression.

PMID- 29600787
TI  - Measure What Can Be Measured: Multimodal Examination of the Atrial Fibrillation
      Substrate.

PMID- 29600788
TI  - Transient Rotor Activity During Prolonged 3-Dimensional Phase Mapping in Human
      Persistent Atrial Fibrillation.
AB  - OBJECTIVES: This study sought to validate a 3-dimensional (3D) phase mapping
      system and determine the distribution of dominant propagation patterns in
      persistent atrial fibrillation (AF). BACKGROUND: Currently available systems
      display phase as simplified 2-dimensional maps. We developed a novel 3D phase
      mapping system that uses the 3D location of basket catheter electrodes and the
      patient's 3D left atrial surface geometry to interpolate phase and create a 3D
      representation of phase progression. METHODS: Six-min AF recordings from the left
      atrium were obtained in 14 patients using the Constellation basket catheter and
      analyzed offline. Exported signals underwent both phase and traditional
      activation analysis and were then visualized using a novel 3D mapping system.
      Analysis involved: 1) validation of phase analysis by comparing beat-to-beat AF
      cycle length calculated using phase inversion with that determined from
      activation timing in the same 20-s segment; 2) validation of 3D phase by
      comparing propagation patterns observed using 3D phase with 3D activation in the
      same 1-min segment; and 3) determining the distribution of dominant propagation
      patterns in 6-min recordings using 3D phase. RESULTS: There was strong agreement
      of beat-to-beat AF cycle length between activation analysis and phase inversion
      (R2 = 0.91). There was no significant difference between 3D activation and 3D
      phase in mean percentage of propagation patterns classified as single wavefronts
      (p = 0.99), focal activations (p = 0.26), disorganized activity (p = 0.76), or
      multiple wavefronts (p = 0.70). During prolonged 3D phase, single wavefronts were
      the most common propagation pattern (50.2%). A total of 34 rotors were seen in 9
      of 14 patients. All rotors were transient with mean duration of 1.0 +/- 0.6 s.
      Rotors were only observed in areas of high electrode density where the
      interelectrode distance was significantly shorter than nonrotor sites (7.4
      [interquartile range: 6.3 to 14.6] vs. 15.3 mm [interquartile range: 10.1 to
      22.2]; p < 0.001). CONCLUSIONS: During prolonged 3D phase mapping, transient
      rotors were observed in 64% of patients and reformed at the same anatomic
      location in 44% of patients. The electrode density of the basket catheter may
      limit the detection of rotors.

PMID- 29600789
TI  - Now You See a Rotor, Now You Don't.

PMID- 29600790
TI  - Biatrial Electrical and Structural Atrial Changes in Heart Failure:
      Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans.
AB  - OBJECTIVES: This study sought to characterize the biatrial substrate in heart
      failure (HF) and persistent atrial fibrillation (PeAF). BACKGROUND: Atrial
      fibrillation (AF) and HF frequently coexist; however, the contribution of HF to
      the biatrial substrate in PeAF is unclear. METHODS: Consecutive patients with
      PeAF and normal left ventricular (NLV) systolic function (left ventricular
      ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF <=45%)
      undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length
      (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial
      appendage for 100 consecutive cycles. After electrical cardioversion, biatrial
      electroanatomic mapping was performed. Complex electrograms, voltage, scarring,
      and conduction velocity were assessed. RESULTS: Forty patients, 20 patients with
      HF (mean age: 62 +/- 8.9 years; AF duration: 15 +/- 11 months; LVEF: 33 +/- 8.4%)
      and 20 with NLV (mean age: 59 +/- 6.7 years; AF duration: 14 +/- 9.1 months; p =
      0.69; mean LVEF: 61 +/- 3.6%; p < 0.001), were enrolled. HF reduced biatrial
      tissue voltage (p < 0.001) with greater voltage heterogeneity (p < 0.001). HF was
      associated with significantly more biatrial fractionation (left atrium [LA]: 30%
      vs. 9%; p < 0.001; right atrium [RA]: 28% vs. 11%; p < 0.001), low voltage (<0.5
      mV) (LA: 23% vs. 6%; p = 0.002; RA: 20% vs 11%; p = 0.006), and scarring (<0.05
      mV) in the LA (p = 0.005). HF was associated with a slower average PVCL (185 vs.
      164 ms; p = 0.016), which correlated significantly with PV antral bipolar voltage
      (R = -0.62; p < 0.001) and fractionation (R = 0.46; p = 0.001). CONCLUSIONS: HF
      is associated with significantly reduced biatrial tissue voltage, fractionation,
      and prolongation of PVCL. Advanced biatrial remodeling may have implications for
      invasive and noninvasive rhythm control strategies in patients with AF and HF.

PMID- 29600791
TI  - Arrhythmogenic Atrial Substrate in Persistent Atrial Fibrillation: Relationship
      to Heart Failure.

PMID- 29600792
TI  - Evaluation of a Strategy Aiming to Enclose the Pulmonary Veins With Contiguous
      and Optimized Radiofrequency Lesions in Paroxysmal Atrial Fibrillation: A Pilot
      Study.
AB  - OBJECTIVES: This study sought to evaluate the safety and the acute and 1 year
      outcomes of an ablation protocol aiming to enclose the PV with a contiguous and
      optimized RF circle by targeting region-specific criteria for lesion depth
      assessed by ablation index and interlesion distance. BACKGROUND: Reconnections
      after pulmonary vein (PV) isolation are explained by insufficient lesion depth
      and/or discontiguity of radiofrequency (RF) lesions. METHODS: A total of 130
      consecutive patients with paroxysmal atrial fibrillation (AF) underwent PV
      encircling using a contact force-sensing catheter. RF was delivered targeting
      interlesion distance <=6 mm and ablation index >=400 at posterior wall and >=550
      at anterior wall. Recurrence was defined as any AF, atrial tachycardia (AT), or
      atrial flutter (AFL) (AF/AT/AFL >30 s) on Holter electrocardiographs at 3, 6, and
      12 months. RESULTS: Procedure and RF time per circle were 155 +/- 28 min and 17
      +/- 5 min, respectively. Incidence of first-pass and adenosine-proof isolation
      were 98% and 98%, respectively. One short-lived transient ischemic attack was
      observed. At 12 months, single-procedure freedom from AF/AT/AFL was 91.3% in
      those 104 patients off antiarrhythmic drug therapy and 96.2% in those 26 patients
      on antiarrhythmic drug therapy. Single-procedure freedom from both AF/AT/AFL and
      antiarrhythmic drug therapy was 73.1%. CONCLUSIONS: This study suggests that an
      ablation protocol respecting strict criteria for lesion depth and contiguity
      results in acute durable PV isolation followed by a high single-procedure
      arrhythmia-free survival at 1 year. A prospective, multicenter trial is ongoing.

PMID- 29600794
TI  - Fluid collection after partial pancreatectomy: EUS drainage and long-term follow
      up.
AB  - Background and Objectives: Postoperative fluid collection due to pancreatic leak
      is the most frequent complication after pancreatic surgery. Endoscopic ultrasound
      (EUS)-guided drainage of post-pancreatic surgery fluid collection is the gold
      standard procedure; however, data on outcomes of this procedure are limited. The
      primary endpoint of our study was relapse over longterm followup, and the
      secondary endpoint was the efficiency and safety of EUS-guided drainage of post
      pancreatic surgery fluid collection. Patients and Methods: This retrospective
      study was conducted at a single center from December 2008 to April 2016. Global
      morbidity was defined as the occurrence of an event involving additional
      endoscopic procedures, hospitalization, or interventional radiologic or surgical
      procedures. EUS-guided drainage was considered a clinical failure if surgery was
      required to treat a relapse after stent removal. Results: Fortyone patients were
      included. The technical success rate was 100%. Drainage was considered a clinical
      success in 93% (39/41) of cases. Additionally, 19 (46%) complications were
      identified as global morbidity. The duration between surgery and EUS-guided
      drainage was not a significantly related factor for morbidity rate (P = 0.8);
      however, bleeding due to arterial injuries (splenic artery and gastroduodenal
      artery) from salvage drainage procedures occurred within 25 days following the
      initial surgery. There was no difference in survival between patients with and
      without complications. No relapse was reported during the followup (median: 44.75
      months; range: 29.24 to 65.74 months). Conclusion: EUSguided drainage for post
      pancreatic surgery fluid collection was efficient with no relapse during longterm
      followup. Morbidity rate was independent of the duration between the initial
      surgery and EUS-guided drainage; however, bleeding risk was likely more important
      in cases of early drainage.

PMID- 29600795
TI  - No effect of abstinence time on nerve electrophysiological test in premature
      ejaculation patients.
AB  - The nerve electrophysiological tests may differentiate the treatment of primary
      premature ejaculation (PPE) in our previous studies. However, no study verifies
      if the results will be affected by abstinence time. From January to December in
      2016, fifty PPE patients ejaculated within 2 min and 28 control subjects were
      enrolled. The nerve electrophysiological tests, including dorsal nerve
      somatosensory evoked potential (DNSEP), glans penis somatosensory evoked
      potential (GPSEP), and penile sympathetic skin response (PSSR), were recorded
      before and immediately after ejaculation. The abstinence day was not correlated
      with the latencies of SEPs or PSSR neither in PE group (P = 0.170, 0.064, and
      0.122, respectively) nor in control group (P = 0.996, 0.475, and 0.904,
      respectively). No statistically differences were found in the latencies of SEPs
      and PSSR before and after ejaculation in PE patients (P = 0.439, 0.537, and
      0.576, respectively) or control subjects (P = 0.102, 0.198, and 0.363,
      respectively). Thus, abstinence time does not interfere with the nerve
      electrophysiological test, which is stable in determining the nerve function of
      PPE patients.

PMID- 29600796
TI  - Rapid screening for Klinefelter syndrome with a simple high-resolution melting
      assay: a multicenter study.
AB  - Klinefelter syndrome (KS) is the set of symptoms that result from the presence of
      an extra X chromosome in males. Postnatal population-based KS screening will
      enable timely diagnosis of this common chromosomal disease, providing the
      opportunity for early intervention and therapy at the time point when they are
      most effective and may prevent later symptoms or complications. Therefore,
      through this study, we introduced a simple high-resolution melting (HRM) assay
      for KS screening and evaluated its clinical sensitivity and specificity in three
      medical centers using 1373 clinical blood samples. The HRM assay utilized a
      single primer pair to simultaneously amplify specific regions in zinc finger
      protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS,
      the ratios of ZFX/ZFY are altered compared to those in normal males. As a result,
      the specific melting profiles differ and can be differentiated during data
      analysis. This HRM assay displayed high analytical specificity over a wide range
      of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for
      detecting KS mosaicism, and high clinical sensitivity (100%) and specificity
      (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD
      per sample), easy to perform and automatic, and compatible with both whole blood
      samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal
      population-based KS screening tool that can be used for different age groups.

PMID- 29600797
TI  - Authors' reply.

PMID- 29600798
TI  - A review of pulse therapy in 74 patients with pemphigus.

PMID- 29600799
TI  - Whole exome sequencing in a multi-generation family from India reveals a genetic
      variation c.10C>T (p.Gln4Ter) in keratin 5 gene associated with Dowling-Degos
      disease.

PMID- 29600800
TI  - Hypertonic Saline Alleviates Brain Edema After Traumatic Brain Injury via
      Downregulation of Aquaporin 4 in Rats.
AB  - BACKGROUND Hypertonic saline (HS) has been successfully used for treatment of
      various forms of brain edema. Decreased expression of aquaporin (AQP)4 and pro
      inflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)
      1b have been linked to edema pathogenesis. This study examined the effect of 3%
      HS on brain edema in a rat model of traumatic brain injury (TBI). MATERIAL AND
      METHODS Sprague-Dawley rats were subjected to TBI induced by a controlled
      cortical impactor. The HS group was injected with 3% NaCl until the end of the
      study period. AQP4, TNF-alpha, IL-1beta, and caspase-3 levels were measured by
      Western blotting, immunohistochemistry, enzyme-linked immunosorbent assay, and
      quantitative real-time PCR. Brain water content was also measured. Apoptotic
      cells in brain tissue were detected with terminal deoxynucleotidyl transferase
      dUTP nick-end labeling. Brain water content decreased following treatment with 3%
      HS relative to the TBI group. RESULTS This was accompanied by decreases in AQP4,
      TNF-alpha, and IL-1beta mRNA and protein levels. TBI resulted in increases in
      caspase-3 mRNA expression and the number of apoptotic cells; treatment with 3% HS
      suppressed apoptosis as compared to the TBI group. CONCLUSIONS Treatment with 3%
      HS ameliorated TBI-induced brain edema, possibly by suppressing brain edema, pro
      inflammatory cytokine expression, and apoptosis.

PMID- 29600801
TI  - Author Correction: The scaffold protein p140Cap limits ERBB2-mediated breast
      cancer progression interfering with Rac GTPase-controlled circuitries.
AB  - This corrects the article DOI: 10.1038/ncomms14797.

PMID- 29600802
TI  - Publisher Correction: Hysteresis of ligand binding in CNGA2 ion channels.
AB  - This corrects the article DOI: 10.1038/ncomms3866.

PMID- 29600803
TI  - Publisher Correction: Simultaneous overactivation of Wnt/beta-catenin and TGFbeta
      signalling by miR-128-3p confers chemoresistance-associated metastasis in NSCLC.
AB  - This corrects the article DOI: 10.1038/ncomms15870.

PMID- 29600804
TI  - Author Correction: Attenuation of RNA polymerase II pausing mitigates BRCA1
      associated R-loop accumulation and tumorigenesis.
AB  - This corrects the article DOI: 10.1038/ncomms15908.

PMID- 29600805
TI  - Author Correction: Menin enhances c-Myc-mediated transcription to promote cancer
      progression.
AB  - This corrects the article DOI: 10.1038/ncomms15278.

PMID- 29600806
TI  - Introduction: Impacting the Social Determinants of Health through a Regional
      Academic-Community Partnership: The Experience of the Mid-South Transdisciplinary
      Collaborative Center for Health Disparities Research.
AB  - Objective: The purpose of this article is to describe the background and
      experience of the Academic-Community Engagement (ACE) Core of the Mid-South
      Transdisciplinary Collaborative Center for Health Disparities Research (Mid-South
      TCC) in impacting the social determinants of health through the establishment and
      implementation of a regional academic-community partnership. Conceptual
      Framework: The Mid-South TCC is informed by three strands of research: the social
      determinants of health, the socioecological model, and community-based
      participatory research (CBPR). Combined, these elements represent a science of
      engagement that has allowed us to use CBPR principles at a regional level to
      address the social determinants of health disparities. Results: The ACE Core
      established state coalitions in each of our founding states-Alabama, Louisiana,
      and Mississippi-and an Expansion Coalition in Arkansas, Tennessee, and Kentucky.
      The ACE Core funded and supported a diversity of 15 community engaged projects at
      each level of the socioecological model in our six partner states through our
      community coalitions. Conclusion: Through our cross-discipline, cross-regional
      infrastructure developed strategically over time, and led by the ACE Core, the
      Mid-South TCC has established an extensive infrastructure for accomplishing our
      overarching goal of investigating the social, economic, cultural, and
      environmental factors driving and sustaining health disparities in obesity and
      chronic illnesses, and developing and implementing interventions to ameliorate
      such disparities.

PMID- 29600807
TI  - Identifying the best methods to assess adiposity and metabolic risk in children.

PMID- 29600808
TI  - Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive
      Impairment in Older Adults in Primary Care.
AB  - STUDY OBJECTIVE: To determine the influence of anticholinergic medications on
      transitions in cognitive diagnosis of older adults in primary care. DESIGN: This
      observational cohort study was conducted over a mean follow-up of 3.2 years.
      Anticholinergic exposure was defined by pharmacy dispensing and claims records.
      Cognitive diagnosis was performed by an expert panel at baseline and annually up
      to 4 years. DATA SOURCE: Medication exposure and other clinical data were
      extracted from the Indiana Network for Patient Care (INPC). The cognitive
      diagnosis was derived from a cognitive screening and diagnosis study.
      PARTICIPANTS: A total of 350 adults 65 years and older without dementia and
      receiving primary care in a safety net health care system. MEASUREMENT AND MAIN
      RESULTS: Cognitive diagnosis followed a two-phase screening and consensus-based
      neuropsychiatric examination to determine a baseline diagnosis as normal
      cognition, mild cognitive impairment (MCI), or dementia, with a follow-up
      neuropsychiatric examination and consensus-based diagnosis repeated annually. The
      Anticholinergic Cognitive Burden scale was used to identify anticholinergics
      dispensed up to 10 years before enrollment and annually throughout the study. A
      total standard daily dose of anticholinergics was calculated by using pharmacy
      dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic
      assessments were completed over a mean follow-up of 3.2 years. Compared with
      stable cognition, increasing use of strong anticholinergics calculated by total
      standard daily dose increased the odds of transition from normal cognition to MCI
      (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, p = 0.0342).
      Compared with stable MCI, strong anticholinergics did not influence the reversion
      of MCI to normal cognition (OR 0.95, 95% CI 0.86-1.05, p = 0.3266). CONCLUSION:
      De-prescribing interventions in older adults with normal cognition should test
      anticholinergics as potentially modifiable risk factors for cognitive impairment.

PMID- 29600809
TI  - Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The
      randomized, controlled ROSE trial.
AB  - OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal
      lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal
      lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial
      recruited adults eligible for open surgery among 14 centers in the USA, UK, and
      India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial
      structures, or standardized ATL. Outcomes were seizure remission (absence of
      disabling seizures between 25 and 36 months), verbal memory (VM), and quality of
      life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27
      in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved
      seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95%
      confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean
      VM changes from baseline for 21 English-speaking, dominant-hemisphere patients
      did not differ between groups; consistent worsening occurred in 36% of SRS and
      57% of ATL patients. QOL improved with seizure remission. Adverse events were
      anticipated cerebral edema and related symptoms for some SRS patients, and
      cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These
      data suggest that ATL has an advantage over SRS in terms of proportion of seizure
      remission, and both SRS and ATL appear to have effectiveness and reasonable
      safety as treatments for MTLE. SRS is an alternative to ATL for patients with
      contraindications for or with reluctance to undergo open surgery.

PMID- 29600810
TI  - Tinea pedis acquired in mosques?
AB  - We present four cases of interdigital tinea pedis in Italian tourists which was
      probably acquired in Turkish mosques and holy Muslim places. In all patients
      mycological examinations were positive for Trichophyton rubrum. All patients were
      successfully treated with bifonazole cream (one application/day for three weeks).
      It is advisable for tourists to wear socks when visiting mosques and holy Muslim
      places.

PMID- 29600811
TI  - Outcome prediction in patients with acute repetitive seizures: Application of the
      Status Epilepticus Severity Score.
AB  - Acute repetitive seizures (ARS) pose a risk of hospital admission with status
      epilepticus and a mortality threat, which underscores the need for the early
      prediction of a clinical course. Unfortunately, little attention has been given
      to ARS in this context, even though we possess the appropriate predictive tools
      for the stages of status epilepticus. Therefore, the main aim of this study was
      to assess the prognostic value of the Status Epilepticus Severity Score (STESS)
      in the population of patients with ARS. The study included a population of 200
      patients. Almost half of the patients had achieved seizure cessations after
      diazepam administration, whereas 19.5% progressed to status epilepticus despite
      antiepileptic drug treatment. Mortality reached 10.5% of the total population.
      The receiver operating characteristic (ROC) curve for prediction of death by the
      STESS had an area under the curve (AUC) of 0.901, with an optimal cutoff point
      for discrimination >=2 (sensitivity 0.95, specificity 0.71, and Youden index
      0.66). Hosmer-Lemeshow indicated good calibration of the STESS (chi-square
      goodness-of-fit test = 3.24; P = .919). The study shows excellent effectiveness
      of the STESS in the prognosis of the clinical course in patients with ARS. STESS
      may be a valuable tool for the proper planning of diagnostic and therapeutic
      activities in this population.

PMID- 29600812
TI  - Ion trajectory simulations of a conical octopole ion guide and its comparison
      with a parallel one in chemical ionization mass spectrometric applications.
AB  - RATIONALE: Focusing and transmission are important characteristics of ion
      transportation in mass spectrometric applications. An ion guide device is an
      essential component in a mass spectrometer, especially when chemical ionization
      is employed. We present a conical octopole ion guide and its comparison with a
      parallel counterpart for simulating the ion trajectories through the ion guide
      and the quadrupole mass analyzer. METHODS: Ion trajectory simulations using
      SIMION 8.0 were performed to evaluate the performance of both conical and
      parallel octopole ion guides and the overall ion transmission through combining
      the octopole ion guide and the quadrupole mass analyzer in the mass spectrometer.
      Through the simulations, parameters that control the ion guide were optimized for
      the focus and transport of weakly bonded cluster ions, including the DC bias
      voltage, the frequency and the amplitude of the sine wave applied to the guide.
      RESULTS: The results from ion trajectory simulations showed that the ion beam can
      be highly focused from initially 10 mm down to 2 mm in diameter for the conical
      octopole ion guide. The transmission efficiencies are dependent on the mass of
      the ion, the frequency and amplitude of the radiofrequency waveform applied to
      the octopoles. The simulated overall transmission efficiencies of the conical ion
      guide are consistent with the observed sensitivities from the previously reported
      calibration experiments in the low-mass region but are much higher than those in
      the high-mass region (i.e., masses greater than 400 amu). CONCLUSIONS: The
      simulations showed that the conical octopole ion guide can efficiently transport
      ions with high focusing through differentially pumped vacuum chambers. However,
      the overall transmission efficiencies of the conical octopole ion guide are in
      general lower than the parallel one when combined with the quadrupole mass
      analyzer based on the assumed exponential pressure gradient along the axial of
      the octopole ion guide.

PMID- 29600816
TI  - Comparison of chlorhexidine-isopropanol with isopropanol skin antisepsis for
      prevention of surgical-site infection after abdominal surgery.
AB  - BACKGROUND: Prevention of surgical-site infection (SSI) has received increasing
      attention. Clinical trials have focused on the role of skin antisepsis in
      preventing SSI. The benefit of combining antiseptic chlorhexidine with alcohol
      has not been compared with alcohol-based skin preparation alone in a prospective
      controlled clinical trial. METHODS: Between August and October 2014, patients
      undergoing abdominal surgery received preoperative skin antisepsis with 70 per
      cent isopropanol (PA). Those treated between November 2014 and January 2015
      received 2 per cent chlorhexidine with 70 per cent isopropanol (CA). The primary
      endpoint was SSI on postoperative day (POD) 10, which was evaluated using
      univariable analysis, and a multivariable logistic regression model correcting
      for known independent risk factors for SSI. The study protocol was published in
      the German Registry of Clinical Studies (DRKS00011174). RESULTS: In total, 500
      patients undergoing elective midline laparotomy were included (CA 221, PA 279).
      The incidence of superficial and deep SSIs was significantly different on POD 10:
      14 of 212 (6.6 per cent) among those treated with CA and 32 of 260 (12.3 per
      cent) in those who received PA (P = 0.038). In the multivariable analysis, skin
      antisepsis with CA was an independent factor for reduced incidence of SSI on POD
      10 (P = 0.034). CONCLUSION: This study showed a benefit of adding chlorhexidine
      to alcohol for skin antisepsis in reducing early SSI compared with alcohol alone.

PMID- 29600817
TI  - Nurses' perception of how an e-message system influences cross-sectoral
      communication: A qualitative study.
AB  - AIM: To investigate hospital and home care nurses' experiences on how an e
      message system influences cross-sectoral communication 2 years after
      introduction. BACKGROUND: Cross-sectoral communication is identified as the main
      barrier for high quality in transitional care. An e-message system was introduced
      to ensure dialogue and precise and useful information exchange. METHODS: Nurses
      from one hospital and six collaborating municipalities were included. Semi
      structured focus group interviews and participation observation was conducted and
      data were analysed using content analysis. RESULTS: The e-message system was used
      in both sectors but did not promote cross-sectoral dialogue. The home care nurses
      expressed distrust in the information from the hospital. The hospital nurses'
      intention was to provide relevant and accurate information but their main focus
      was to fulfil the standards within the system rather than the quality of the
      information exchanged. CONCLUSIONS: The e-message system supports a one-way
      information flow, rather than the intended loop of information exchange and
      dialogue. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should recognise
      that although an e-message system is being used in a clinical setting, it may not
      support exchange of high-quality information and dialogue. Focus must be on both
      standards as well as quality when new systems are introduced.

PMID- 29600818
TI  - Emergence of Uranium as a Distinct Metal Center for Building Intrinsic X-ray
      Scintillators.
AB  - The combination of high atomic number and high oxidation state in UVI materials
      gives rise to both high X-ray attenuation efficiency and intense green
      luminescence originating from ligand-to-metal charge transfer. These two features
      suggest that UVI materials might act as superior X-ray scintillators, but this
      postulate has remained substantially untested. Now the first observation of
      intense X-ray scintillation in a uranyl-organic framework (SCU-9) that is
      observable by the naked eye is reported. Combining the advantage in minimizing
      the non-radiative relaxation during the X-ray excitation process over those of
      inorganic salts of uranium, SCU-9 exhibits a very efficient X-ray to green light
      luminescence conversion. The luminescence intensity shows an essentially linear
      correlation with the received X-ray intensity, and is comparable with that of
      commercially available CsI:Tl. SCU-9 possesses an improved X-ray attenuation
      efficiency (E>20 keV) as well as enhanced radiation resistance and decreased
      hygroscopy compared to CsI:Tl.

PMID- 29600819
TI  - Association Between Medication Adherence and the Outcomes of Heart Failure.
AB  - BACKGROUND: Previous studies of heart failure patients demonstrated an
      association between cardiovascular medication adherence and hospitalizations or a
      composite end point of hospitalization and death. Few studies have assessed the
      impact of treatment adherence within large general medical populations that
      distinguish the health outcomes of emergency department visits, hospitalization,
      and death. OBJECTIVE: To determine the association of incremental cardiovascular
      medication adherence on emergency department visits, hospitalization, and death
      in adult heart failure patients in Indiana. DESIGN: Retrospective cohort study
      conducted using electronic health record data from the statewide Indiana Network
      for Patient Care between 2004 and 2009. METHODS: Patients were at least 18 years
      of age with a diagnosis of heart failure and prescribed at least one
      cardiovascular medication for heart failure. Adherence was measured as the
      proportion of days covered (PDC) using pharmacy transaction data. Clinical end
      points included emergency department visits, hospital admissions, length of
      hospital stay, and mortality. Generalized linear models were used to determine
      the effect of a 10% increase in PDC on clinical end points adjusting for age,
      sex, race, Charlson Comorbidity Index, and medications. RESULTS: Electronic
      health records were available for 55,312 patients (mean age +/- standard
      deviation 68 +/- 16 yrs; 54% women; 65% white). Mean PDC for all heart failure
      medications was 63% +/- 23%. For every 10% increase in PDC, emergency department
      visits decreased 11% (rate ratio [RR] 0.89, 95% confidence interval [CI] 0.89
      0.89), hospital admissions decreased 6% (RR 0.94, 95% CI 0.94-0.94), total length
      of hospital stay decreased 1% (RR 0.99, 95% CI 0.99-1.00), and all-cause
      mortality decreased 9% (odds ratio 0.91; 95% CI 0.90-0.92). CONCLUSION:
      Incremental medication adherence was associated with reductions in emergency
      department visits, hospital admissions, length of hospital stay, and all-cause
      mortality.

PMID- 29600820
TI  - Connection-based and object-based grouping in multiple-object tracking: A
      developmental study.
AB  - Developmental research on Gestalt laws has previously revealed that, even as
      young as infancy, we are bound to group visual elements into unitary structures
      in accordance with a variety of organizational principles. Here, we focus on the
      developmental trajectory of both connection-based and object-based grouping, and
      investigate their impact on object formation in participants, aged 9-21 years old
      (N = 113), using a multiple-object tracking paradigm. Results reveal a main
      effect of both age and grouping type, indicating that 9- to 21-year-olds are
      sensitive to both connection-based and object-based grouping interference, and
      tracking ability increases with age. In addition to its importance for typical
      development, these results provide an informative baseline to understand clinical
      aberrations in this regard. Statement of contribution What is already known on
      this subject? The origin of the Gestalt principles is still an ongoing debate:
      Are they innate, learned over time, or both? Developmental research has revealed
      how each Gestalt principle has its own trajectory and unique relationship to
      visual experience. Both connectedness and object-based grouping play an important
      role in object formation during childhood. What does this study add? The study
      identifies how sensitivity to connectedness and object-based grouping evolves in
      individuals, aged 9-21 years old. Using multiple-object tracking, results reveal
      that the ability to track multiple objects increases with age. These results
      provide an informative baseline to understand clinical aberrations in different
      types of grouping.

PMID- 29600821
TI  - An unusual presentation of a common condition: Allergic contact dermatitis.
AB  - Allergic contact dermatitis commonly affects patients with chronic venous leg
      ulcers and can contribute to impaired wound healing. Many allergens have been
      identified, and despite the use of advanced dressings, the incidence of allergy
      has remained high. We discuss an unusual presentation of allergic contact
      dermatitis in a patient with a chronic wound. The patient's history was
      consistent with a recurrent venous leg ulcer, but on this occasion, the wound
      continued to deteriorate despite optimal treatment. This prompted further
      investigation, which included patch testing. Although the clinical features were
      not suggestive of allergy, the patch test was positive for several allergens,
      including Atrauman(r) dressings, which the patient was using at the time. This
      case highlights the importance of regular reassessment and accurate diagnosis for
      the management of chronic wounds. It also demonstrates that allergic contact
      dermatitis can contribute to delayed wound healing without causing the classical
      clinical features of inflammation of the surrounding skin, and even
      hypoallergenic, non-adherent dressings can be sensitising.

PMID- 29600822
TI  - Effect of an experiential learning-based programme to foster competence among
      nurse managers.
AB  - AIM: The present study aimed to examine the effect of providing an experiential
      learning-based programme to foster competence among nurse managers in the early
      years of their supervisory roles. BACKGROUND: Nurse managers take supervisory
      positions without being sufficiently prepared for the task and therefore often
      experience difficultly in the early years of managerial roles. They need support
      from their supervisor and require opportunities for development. METHODS: We
      developed an experiential learning-based programme for nurse managers in the
      first 3 years of a supervisory role. Sixty-three nurse managers and their
      supervisors were enrolled. The programme was evaluated using a one-group pretest
      posttest design. The outcome measures were experiential learning, knowledge,
      social support, competency as a nurse manager, and sense of coherence. Outcomes
      were compared using paired t tests. RESULTS: Nurse managers showed significantly
      improved experiential learning (p = .001), knowledge (p < .001) and competence as
      a nurse manager (p = .002) after participating in this programme. CONCLUSION:
      This programme increased knowledge, promoted experiential learning, and improved
      competence among nurse managers. IMPLICATIONS FOR NURSING MANAGEMENT: This
      experiential learning-based programme for nurse managers in the early years of a
      supervisory role fostered competence among nurse managers.

PMID- 29600823
TI  - Realization of Walnut-Shaped Particles with Macro-/Mesoporous Open Channels
      through Pore Architecture Manipulation and Their Use in Electrocatalytic Oxygen
      Reduction.
AB  - Herein we report a simple dual-soft-template approach to prepare walnut-shaped
      macro-/mesoporous polydopamine particles with diameter of ca. 270 nm, highly
      accessible bicontinuous channels and wide pore size distribution from ca. 20 nm
      to ca. 95 nm. This approach provides great opportunities to tailor the soft
      template-directed assembly processes and generate various polydopamine particles
      with controllable mesophase curvature. Walnut-shaped mesoporous carbon particles
      with large open mesochannels in the range of ca. 13 nm to ca. 50 nm can be
      fabricated by subsequent thermal treatment under nitrogen atmosphere. Lastly, we
      demonstrate that the as-derived walnut-shaped carbon particles manifest enhanced
      electrocatalytic performance for oxygen reduction reaction in alkaline
      electrolyte.

PMID- 29600824
TI  - Prospective Open-label Trial of Early Concomitant Vasopressin and Norepinephrine
      Therapy versus Initial Norepinephrine Monotherapy in Septic Shock.
AB  - PURPOSE: Delays in achieving target mean arterial pressure (MAP) are associated
      with increased morbidity and mortality in patients with septic shock. This trial
      was conducted to test the hypothesis that early concomitant treatment with
      vasopressin and norepinephrine reduces the time to achieve and maintain target
      MAP compared with initial norepinephrine monotherapy. METHODS: A single-center
      prospective open-label trial was conducted in patients with septic shock between
      November 2015 and June 2016 at a medical intensive care unit in an academic
      medical center. Initial norepinephrine monotherapy was initiated between November
      2015 and February 2016. Between March and June 2016, vasopressin was initiated
      within 4 hours of norepinephrine. The primary outcome was time to achieving and
      maintaining MAP of 65 mm Hg for at least 4 hours that was compared between groups
      using the Student t test and examined using the Kaplan-Meier curve (Clinical
      Trials registration: NCT02454348). RESULTS: Eighty-two patients were included (41
      in each group). Patients treated with early concomitant vasopressin and
      norepinephrine more frequently had a positive culture (59% vs 37%, p=0.05) and
      grew nonlactose fermenting gram-negative bacilli (34% vs 10%, p=0.01) compared
      with patients treated with norepinephrine monotherapy, respectively. The median
      time to achieve and maintain MAP occurred faster in the early concomitant
      vasopressin and norepinephrine group, at 5.7 hours (interquartile range [IQR] 1.7
      10.3 hrs), compared with 7.6 hours (IQR 3.6-16.7 hrs, p=0.058) in the
      norepinephrine group. Durations of therapy for norepinephrine or vasopressin,
      amount of norepinephrine received in the first 24 hours, norepinephrine dosage
      when MAP was achieved and maintained, maximum norepinephrine dosage, and
      mortality were similar between groups. CONCLUSION: Patients treated with early
      concomitant vasopressin and norepinephrine achieved and maintained MAP of 65 mm
      Hg faster than those receiving initial norepinephrine monotherapy, suggesting
      that overcoming vasopressin deficiency sooner may reduce the time patients spend
      in the early phase of septic shock.

PMID- 29600825
TI  - Depression comorbidity in epileptic rats is related to brain glucose
      hypometabolism and hypersynchronicity in the metabolic network architecture.
AB  - OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common types of
      epilepsy syndromes in the world. Depression is an important comorbidity of
      epilepsy, which has been reported in patients with TLE and in different
      experimental models of epilepsy. However, there is no established consensus on
      which brain regions are associated with the manifestation of depression in
      epilepsy. Here, we investigated the alterations in cerebral glucose metabolism
      and the metabolic network in the pilocarpine-induced rat model of epilepsy and
      correlated it with depressive behavior during the chronic phase of epilepsy.
      METHODS: Fluorodeoxyglucose (18 F-FDG) was used to investigate the cerebral
      metabolism, and a cross-correlation matrix was used to examine the metabolic
      network in chronically epileptic rats using micro-positron emission tomography
      (microPET) imaging. An experimental model of epilepsy was induced by pilocarpine
      injection (320 mg/kg, ip). Forced swim test (FST), sucrose preference test (SPT),
      and eating-related depression test (ERDT) were used to evaluate depression-like
      behavior. RESULTS: Our results show an association between epilepsy and
      depression comorbidity based on changes in both cerebral glucose metabolism and
      the functional metabolic network. In addition, we have identified a significant
      correlation between brain glucose hypometabolism and depressive-like behavior in
      chronically epileptic rats. Furthermore, we found that the epileptic depressed
      group presents a hypersynchronous brain metabolic network in relation to the
      epileptic nondepressed group. SIGNIFICANCE: This study revealed relevant
      alterations in glucose metabolism and the metabolic network among the brain
      regions of interest for both epilepsy and depression pathologies. Thus it seems
      that depression in epileptic animals is associated with a more diffuse
      hypometabolism and altered metabolic network architecture and plays an important
      role in chronic epilepsy.

PMID- 29600826
TI  - "Leading Better Care": An evaluation of an accelerated coaching intervention for
      clinical nursing leadership development.
AB  - AIM: Outcomes of an accelerated co-active coaching intervention for senior
      clinical nursing leadership development. BACKGROUND: Co-active coaching is
      characterized by a whole person approach, commitment to deep learning and
      conscious action through supportive compassionate and courageous coach-coachee
      partnership. The national leadership capabilities framework, "Step into
      Leadership", was used for development and evaluation. METHODS: 116 senior
      clinical nurse leaders attended one face-to-face induction day and received a
      total of 3 hours of one-to-one telephone coaching and two virtual peer group
      facilitated sessions. Evaluation used primarily qualitative descriptive methods
      with iterative review of emerging themes. RESULTS: Capability mapping indicated
      self-leadership development as the most frequently cited need. Improvements in
      self-confidence, capacity for reflection and bringing whole self into the work
      were reported to deliver enhancement in team and service performance.
      CONCLUSIONS: Co-active coaching supported deep analysis by individuals. Focus on
      self, rather than behaviours provoked reflection on perspectives, mindsets,
      beliefs and approaches which can lead to more sustainable behaviour and support
      service change. IMPLICATIONS FOR NURSING MANAGEMENT: Investment in a co-active
      coaching approach offers bespoke support for clinical leaders to develop self
      leadership capability, a precursor to delivering positive impacts on care.

PMID- 29600827
TI  - Special Issue on Chiral Separations Dedicated to Prof. Benedetto Natalini on the
      Occasion of His 70th Birthday.

PMID- 29600828
TI  - An electrical plasma dissection tool for surgical treatment of chronic ulcers:
      Results of a prospective randomised trial.
AB  - Cutaneous ulceration is a difficult medical problem and a major source of
      morbidity for patients. In the surgical treatment of ulcers, debridement is the
      first step, and it can be carried out using several surgical tools. Recently, new
      surgical devices have emerged using plasma-mediated electrical discharges with a
      lower peak temperature. A prospective single-blind trial was conducted on chronic
      ulcers not responsive to common non-surgical management. Patients were randomly
      separated into 2 groups: Group A received surgical debridement with conventional
      electrocautery, and Group B received surgical debridement using the plasma
      mediated device. Histological samples were collected intraoperatively to evaluate
      the thermal damage during the surgical procedure and 2 weeks after surgery to
      evaluate the inflammatory response and collagen deposition. The width of
      coagulation necrosis at the incision margins in Group B was significantly shorter
      compared with Group A (P = .001). The inflammatory cell infiltration showed a
      cellular distribution percentage that was quite equal between the 2 groups. The
      granulation tissue showed an abundant deposition of dense and mature collagen in
      Group B, compared with Group A, where the mature collagen appeared in small
      quantities (P < .001). Microbial culture showed a lower incidence of
      postoperative infections in Group B compared with the control group (P < .05).
      The study demonstrated, based on the results, that the new technology with the
      use of a lower temperature electrosurgical device represents an effective
      therapeutic weapon for the surgical treatment of skin ulcers, both vascular and
      extravascular types.

PMID- 29600829
TI  - Our experience of the necessity of adenoidectomy or adenotonsillectomy at the
      time of ventilation tube insertion in 11 941 children with middle ear effusion.

PMID- 29600830
TI  - Evaluation of Kinase Inhibitor Selectivity Using Cell-based Profiling Data.
AB  - Kinases are among the most heavily investigated drug targets and inhibition of
      kinases and kinase-dependent signaling has become a paradigm for therapeutic
      intervention. Kinase inhibitors and associated activity data have increasing 'big
      data' character, which presents challenges for computational analysis, but also
      unprecedented opportunities for learning from compound data and for data-driven
      medicinal chemistry. Herein, publicly available kinase inhibitor data are
      evaluated and a number of characteristics are discussed. In addition, selectivity
      of clinical kinase inhibitors is explored computationally on the basis of
      recently reported cell-based profiling data. For inhibitors shared by pairs of
      kinases, selectivity profiles were generated and a variety of selective
      inhibitors were identified. Uni-directional selectivity profiles revealed
      inhibitors that were selective for one kinase over the other, while bi
      directional profiles uncovered compounds with inverted selectivity for paired
      kinases.

PMID- 29600831
TI  - Synthesis of Densely Packaged, Ultrasmall Pt02 Clusters within a Thioether
      Functionalized MOF: Catalytic Activity in Industrial Reactions at Low
      Temperature.
AB  - The gram-scale synthesis, stabilization, and characterization of well-defined
      ultrasmall subnanometric catalytic clusters on solids is a challenge. The
      chemical synthesis and X-ray snapshots of Pt02 clusters, homogenously distributed
      and densely packaged within the channels of a metal-organic framework, is
      presented. This hybrid material catalyzes efficiently, and even more importantly
      from an economic and environmental viewpoint, at low temperature (25 to 140 
      degrees C), energetically costly industrial reactions in the gas phase such as
      HCN production, CO2 methanation, and alkene hydrogenations. These results open
      the way for the design of precisely defined catalytically active ultrasmall metal
      clusters in solids for technically easier, cheaper, and dramatically less
      dangerous industrial reactions.

PMID- 29600833
TI  - Sigmoid diverticulitis in elderly patients: a rare cause of right iliac fossa
      pain.

PMID- 29600834
TI  - Colovesical fistula complicating diverticular disease: diagnosis and surgical
      management in elderly.

PMID- 29600832
TI  - Bullous pemphigoid: Italian guidelines adapted from the EDF/EADV guidelines.
AB  - Bullous pemphigoid is the most common autoimmune subepidermal blistering disease
      of the skin and mucous membranes. This disease typically affects the elderly and
      presents with itch and localized or generalized bullous lesions. In up to 20% of
      affected patients blister may be completely absent, and only excoriations,
      prurigo-like lesions, eczematous lesions, urticated lesions, and/or infiltrated
      plaques are observed. The disease is significantly associated with neurological
      disorders. The morbidity of bullous pemphigoid and its impact on the quality of
      life are significant. So far, a limited number of national treatment guidelines
      have been proposed, but no common European consensus has emerged. This guideline
      for the treatment of bullous pemphigoid has been developed by an Italian group of
      experts taking in account the Italian legislation and local pharmacological
      governance. Guidelines are adapted from the original article under the guidance
      of the European Dermatology Forum (EDF) in collaboration with the European
      Academy of Dermatology and Venereology (EADV). It summarizes evidence-based and
      expert-based recommendations (S2 level).

PMID- 29600835
TI  - Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant
      chemotherapy and radical surgery.
AB  - BACKGROUND: The aim of this study was to estimate the rate of ovarian metastases
      and recurrences among patients affected by locally advanced stage cancer patients
      (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with
      conservation of ovaries. METHODS: Retrospective evaluation of consecutive
      patients affected by LACC (stage IB2-IIB), treated by NACT followed by radical
      surgery at National Cancer Institute, Milan, Italy, between 1990-2015. RESULTS:
      Overall, 331 patients were included. Stage at presentation included stage IB2,
      IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main
      histotype was squamous cell carcinoma (N.=265, 80.1%) followed by
      adenocarcinoma/adenosquamous (N.=51, 15.4%), and more than half of patients had a
      grade 3 carcinoma. Overall, 102 (30.8%) women had at least one ovary preserved
      during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing
      patients who had ovarian preservation with patients who had not, we observed that
      the two groups were comparable in terms of baseline characteristics. Survival
      outcomes were not influenced by ovarian preservation (disease-free [P=0.93] and
      overall [P=0.65] survivals). One (1%) woman had a localized ovarian recurrence.
      CONCLUSIONS: Our data suggest that ovarian preservation at the time of surgery is
      a safe option among women with LACC after NACT with no detrimental impact on
      oncologic outcome. Further prospective studies are warranted.

PMID- 29600836
TI  - Anorexia nervosa and alcohol use disorders: a change is necessary.

PMID- 29600837
TI  - The effects of functional and traditional strength training on different
      parameters of strength elderly women: a trial randomized and controlled.
AB  - BACKGROUND: Physical exercise is the main strategy for improving physical fitness
      in elderly population. However, it is not clear which training method lead to
      greater adaptations on maximal dynamic strength, muscle power, muscle endurance
      and isometric strength in this population. Thus, our aim was to compare the
      effects of functional and traditional training on these variables in the elderly.
      METHODS: This study lasted twelve weeks, where forty-four elderly women were
      randomly divided into three groups: Functional (FT; n = 18); Traditional (TT; n =
      15); and Control (CG; n = 11). Maximal dynamic strength (Strength) and muscle
      power (Power) tests were performed in pushing (Push), pulling (Pull) and
      squatting (Squat) actions. In addition, isometric strength (ISO) with Hand Grip
      Test (HG) and Isometric Dead Lift Test (ID) and muscle endurance (Endurance) with
      30 s chair stand (CS) and 30 s arm curl (AC) tests were used. RESULTS: Both
      experimental groups improved significantly in Strength (FT: Push 24.9%; Squat
      38.4%; Pull 21.6% / TT: Push 18.2%; Squat 9.8%; Pull 19.2%), Power (FT: Push
      13.6%; Squat 11.6%; Pull 13.6% / TT: Push 18.2%; Squat 9.8%; Pull 19.2%) ISO (FT:
      HG 14,7%; ID 13,6% / TT: HG 19,1%) and Endurance (TF: CS 19.6%; AC 23.8% / TT: CS
      15.5%) with p <= 0,05, except TT in ID (4.4%) and SL (4.6%). There was no
      difference between experimental groups; however, both experimental groups were
      statistically superior to CG. CONCLUSIONS: Both training protocols were equally
      effective in improving different strength manifestations in the elderly.

PMID- 29600838
TI  - Assessing a Medley of Metals: Combined Exposures and Incident Coronary Heart
      Disease.

PMID- 29600839
TI  - Erratum: "A Case-Control Study of Maternal Polybrominated Diphenyl Ether (PBDE)
      Exposure and Cryptorchidism in Canadian Populations".
AB  - [This corrects the article DOI: 10.1289/EHP522.].

PMID- 29600840
TI  - Vesicles Functionalized with a CO-Releasing Molecule for Light-Induced CO
      Delivery.
AB  - In this paper, a new type of methodology to deliver carbon monoxide (CO) for
      biological applications has been introduced. An amphiphilic manganese carbonyl
      complex (1.Mn) incorporated into the 1,2-distearoyl-sn-glycero-3-phosphocholine
      lipid vesicles has been reported first time for the photoinduced release of CO.
      The liposomes (Ves-1.Mn) gradually released CO under light at 365 nm over a
      period of 50 min with a half-time of 26.5 min. The CO-releasing ability of
      vesicles appended with 1.Mn complexes has been confirmed by myoglobin assay and
      infrared study. The vesicles appended with 1.Mn have the advantages of
      biocompatibility, water solubility, and steady and slow CO release. This approach
      could be a rational approach for applying various water-insoluble photoinduced CO
      donors in aqueous media by using vesicles as a nanocarrier for CO release.

PMID- 29600841
TI  - Hierarchically Bicontinuous Porous Copper as Advanced 3D Skeleton for Stable
      Lithium Storage.
AB  - Rechargeable lithium metal anodes (LMAs) with long cycling life have been
      regarded as the "Holy Grail" for high-energy-density lithium metal secondary
      batteries. The skeleton plays an important role in determining the performance of
      LMAs. Commercially available copper foam (CF) is not normally regarded as a
      suitable skeleton for stable lithium storage owing to its relatively
      inappropriate large pore size and relatively low specific surface area. Herein,
      for the first time, we revisit CF and address these issues by rationally
      designing a highly porous copper (HPC) architecture grown on CF substrates
      (HPC/CF) as a three-dimensional (3D) hierarchically bicontinuous porous skeleton
      through a novel approach combining the self-assembly of polystyrene microspheres,
      electrodeposition of copper, and a thermal annealing treatment. Compared to the
      CF skeleton, the HPC/CF skeleton exhibits a significantly improved Li
      plating/stripping behavior with high Coulombic efficiency (CE) and superior Li
      dendrite growth suppression. The 3D HPC/CF-based LMAs can run for 620 h without
      short-circuiting in a symmetric Li/Li@Cu cell at 0.5 mA cm-2, and the
      Li@Cu/LiFePO4 full cell exhibits a high reversible capacity of 115 mAh g-1 with a
      high CE of 99.7% at 2 C for 500 cycles. These results demonstrate the
      effectiveness of the design strategy of 3D hierarchically bicontinuous porous
      skeletons for developing stable and safe LMAs.

PMID- 29600842
TI  - Hexamerization of Geranylgeranylglyceryl Phosphate Synthase Ensures Structural
      Integrity and Catalytic Activity at High Temperatures.
AB  - The cell membranes of all archaea contain ether lipids, and a number of archaea
      are hyperthermophilic. Consequently, the enzymes that catalyze the synthesis of
      membrane ether lipids had to adopt to these rough conditions. Interestingly, the
      enzyme that establishes the first ether bond in these lipids, the
      geranylgeranylglyceryl phosphate synthase (GGGPS), forms hexamers in many
      hyperthermophilic archaea, while also dimeric variants of this enzyme exist in
      other species. We used Methanothermobacter thermautotrophicus GGGPS (mtGGGPS) as
      a model to elucidate the benefit of hexamerization. We studied the
      oligomerization interfaces in detail by introducing disturbing mutations and
      subsequently compared the stability and activity of generated dimeric and
      monomeric variants with the wild-type enzyme. Differential scanning calorimetry
      revealed a biphasic denaturation of mtGGGPS. The temperature of the first
      transition varies and rises with increasing oligomerization state. This first
      phase of denaturation leads to catalytic inactivation, but CD spectroscopy
      indicated only minor changes on the secondary structure level. The residual part
      of the fold is extremely thermostable and denatures in a second phase at
      temperatures >120  degrees C. The analysis of another distant native GGGPS enzyme
      affirms these observations. Molecular dynamics simulations revealed three
      structural elements close to the substrate binding sites with elevated
      flexibility. We assume that hexamerization might stabilize these structures, and
      kinetic studies support this hypothesis for the binding pocket of the substrate
      glycerol 1-phosphate. Oligomerization might thus positively affect the
      thermostability-flexibility trade-off in GGGPS by allowing a higher intrinsic
      flexibility of the individual protomers.

PMID- 29600843
TI  - Entanglement-Based Thermoplastic Shape Memory Polymeric Particles with
      Photothermal Actuation for Biomedical Applications.
AB  - Triggering shape-memory functionality under clinical hyperthermia temperatures
      could enable the control and actuation of shape-memory systems in clinical
      practice. For this purpose, we developed light-inducible shape-memory
      microparticles composed of a poly(d,l-lactic acid) (PDLLA) matrix encapsulating
      gold nanoparticles (Au@PDLLA hybrid microparticles). This shape-memory polymeric
      system for the first time demonstrates the capability of maintaining an
      anisotropic shape at body temperature with triggered shape-memory effect back to
      a spherical shape at a narrow temperature range above body temperature with a
      proper shape recovery speed (37 < T < 45  degrees C). We applied a modified film
      stretching processing method with carefully controlled stretching temperature to
      enable shape memory and anisotropy in these micron-sized particles. Accordingly,
      we achieved purely entanglement-based shape-memory response without chemical
      cross-links in the miniaturized shape-memory system. Furthermore, these shape
      memory microparticles exhibited light-induced spatiotemporal control of their
      shape recovery using a laser to trigger the photothermal heating of doped gold
      nanoparticles. This shape-memory system is composed of biocompatible components
      and exhibits spatiotemporal controllability of its properties, demonstrating a
      potential for various biomedical applications, such as tuning macrophage
      phagocytosis as demonstrated in this study.

PMID- 29600844
TI  - Click Chemical Ligation-Initiated On-Bead DNA Polymerization for the Sensitive
      Flow Cytometric Detection of 3'-Terminal 2'-O-Methylated Plant MicroRNA.
AB  - A versatile flow cytometric strategy is developed for the sensitive detection of
      plant microRNA (miRNA) by coupling the target-templated click nucleic acid
      ligation (CNAL) with on-bead terminal enzymatic DNA polymerization (TEP). Unlike
      ligase-catalyzed ligation reaction, the plant miRNA-templated enzyme-free CNAL
      between two single-stranded DNA (ssDNA) probes, respectively modified with Aza
      dibenzocyclooctyne (Aza-DBCO) and N3, can not only simplify the operation, but
      also achieve a much higher ligation efficiency. More importantly, the undesirable
      nonspecific ligation between the Aza-DBCO- and N3-modified ssDNA, can be
      effectively eliminated by adding Tween-20, which allows the use of cycling CNAL
      (CCNAL) in a background-free manner. So each plant miRNA can template many rounds
      of CNAL reaction to produce numerous ligation products, forming efficient signal
      amplification. The ligated ssDNA can be anchored on the magnetic beads (MBs) with
      the 3'-OH termini exposed outside. Then terminal deoxynucleotidyl transferase
      (TdT), a sequence-independent and template-free polymerase, would specifically
      catalyze the DNA polymerization along these 3'-OH termini on the MBs, forming
      poly(T) tails up to thousands of nucleotides long. Each poly(T) tail allows
      specific binding of numerous 6-carboxyfluorescein (FAM)-labeled poly(A)25
      oligonucleotides to accumulate a lot of fluorophores on the MBs, leading to the
      second step of signal amplification. By integrating the advantages of CCNAL-TEP
      for highly efficient signal amplification and robust MBs signal readout with
      powerful flow cytometer, high sensitivity is achieved and the detection limit of
      plant miRNA has been pushed down to a low level of 5 fM with high specificity to
      well discriminate even single-base difference between miRNA targets.

PMID- 29600845
TI  - Moderate Bacterial Etching Allows Scalable and Clean Delamination of g-C3N4 with
      Enriched Unpaired Electrons for Highly Improved Photocatalytic Water
      Disinfection.
AB  - Delamination treatment is crucial in promoting the activity of bulk graphitic
      carbon nitride (g-C3N4). However, most of the currently used methods of
      exfoliating bulk g-C3N4 to achieve g-C3N4 thin layers suffer from low yield and
      environmental pollution. Herein, we developed a facile bacterial etching approach
      for the preparation of high-quality g-C3N4 nanosheets by exfoliating bulk g-C3N4
      under room temperature. Morphology and physicochemical characterizations show
      that the bacteria-treated g-C3N4 (BT-CN) samples, especially BT-CN-2d, have a
      lamina-like two-dimensional (2D) in-plane porous structure, a significantly
      enlarged specific surface area (82.61 m2 g-1), and a remarkable narrow band gap
      (2.11 eV). X-ray photoelectron spectroscopy and electron paramagnetic resonance
      spectra confirm the dramatic enrichment of unpaired electron in the BT-CN-2d g
      C3N4 nanosheets. EIS spectra and photocurrent tests indicate the fast electron
      transportation. As a result, the representative BT-CN-2d g-C3N4 photocatalyst
      shows an optimal visible light-driven photocatalytic performance in water
      disinfection (fourfold higher than bulk g-C3N4), as well as good cycle stability.
      This moderate and clean bacterial etching process can be realized in tens of gram
      scale in the laboratory and should be readily extended to kilogram scale. The
      present work provides fundamental knowledge about the scalable production of high
      quality g-C3N4 by bioengineering method, offering extendable availability for
      designing and fabricating other functional 2D materials.

PMID- 29600846
TI  - Encapsulation of CH3NH3PbBr3 Perovskite Quantum Dots in MOF-5 Microcrystals as a
      Stable Platform for Temperature and Aqueous Heavy Metal Ion Detection.
AB  - The stability issue of organometallic halide perovskites remains a great
      challenge for future research as to their applicability in different functional
      material fields. Herein, a novel and facile two-step synthesis procedure is
      reported for encapsulation of CH3NH3PbBr3 perovskite quantum dots (QDs) in MOF-5
      microcrystals, where PbBr2 and CH3NH3Br precursors are added stepwise to
      fabricate stable CH3NH3PbBr3@MOF-5 composites. In comparison to CH3NH3PbBr3 QDs,
      CH3NH3PbBr3@MOF-5 composites exhibited highly improved water resistance and
      thermal stability, as well as better pH adaptability over a wide range.
      Luminescent investigations demonstrate that CH3NH3PbBr3@MOF-5 composites not only
      featured excellent sensing properties with respect to temperature changes from 30
      to 230  degrees C but also exhibited significant selective luminescent response
      to several different metal ions in aqueous solution. These outstanding
      characteristics indicate that the stable CH3NH3PbBr3@MOF-5 composites are
      potentially interesting for application in fluorescence sensors or detectors.

PMID- 29600847
TI  - Total Synthesis of (+/-)-Minfiensine via a Formal [3+2] Cycloaddition.
AB  - (+/-)-Minfiensine (1) was synthesized in 10 steps in 26% overall yield with the
      1,2,3,4-tetrahydro-9a,4a-iminoethanocarbazole core constructed through a [3+2]
      cycloaddition reaction between indole and an azaoxyallylic cation.

PMID- 29600848
TI  - Trichorenins A-C, Algicidal Tetracyclic Metabolites from the Marine-Alga
      Epiphytic Fungus Trichoderma virens Y13-3.
AB  - Three novel polyketide-like metabolites, trichorenins A-C (1-3), with a unique
      tetracyclic carbon skeleton were obtained from the culture of Trichoderma virens
      Y13-3, an epiphyte of the marine red alga Gracilaria vermiculophylla. Their
      structures and relative configurations were established by analysis of 1D/2D NMR
      and MS data, and their absolute configurations were unequivocally assigned by X
      ray diffraction and ECD spectra aided by quantum chemical calculations. Compounds
      1-3 exhibited potent inhibition against two marine phytoplankton species,
      Chattonella marina and Karlodinium veneficum.

PMID- 29600849
TI  - Isomerization Reaction of mer- to fac-Tris(2-phenylpyridinato-N,C2')Iridium(III)
      Monitored by Using Surface-Enhanced Raman Spectroscopy.
AB  - We developed a new method by enclosing the complex tris(2-phenylpyridinato
      N,C2')Iridium(III), Ir(ppy)3 with surfactant cetyltrimethylammonium bromide
      (CATB), coated with a thin layer of silica then bonded to the surface of silver
      nanoparticle. These samples were used to acquire surface-enhanced Raman
      scattering (SERS) spectra. The thickness of silica layer was controlled to have
      efficient phosphorescence quenching and Raman enhancement by metal nanoparticle.
      The SERS spectra of fac- and mer-Ir(ppy)3, recorded at 633 nm excitation, display
      distinct ring breathing mode features because the total symmetric vibrational
      bands were enhanced. This provides a convenient means to differentiate these
      isomers with great sensitivity and to study their isomerization process. A direct
      conversion reaction of mer- to fac- isomerization is identified with time
      constant 3.1 min when mer was irradiated with Xe light. Via thermal activation,
      under moderate conditions (pH 5.5 and 343 K), we observed an intermediate
      particularly with new bands 320/662 cm-1 after heating for 17.5 h, and then those
      bands disappeared to form fac-Ir(ppy)3. On the basis of DFT calculations, the
      intermediate is proposed to contain octahedral N-N Ir(ppy)3-HO-silica structure;
      band at 320 cm-1 is assigned to iridium oxygen stretching mode nuIr-O of this
      intermediate. Under acidic conditions, pH 1-2 catalyzed by silanol in silica,
      byproduct with band at 353 cm-1 was observed. According to the SERS bands and the
      calculation, this byproduct is assigned to be iridium(III) siloxide, and the new
      band is assigned to nuIr-O.

PMID- 29600850
TI  - ReFlex3D: Refined Flexible Alignment of Molecules Using Shape and Electrostatics.
AB  - We present an algorithm, ReFlex3D, for the refinement of flexible molecular
      alignments based on their three-dimensional shape and electrostatic properties.
      The algorithm is designed to be used with fast conformer generators to refine an
      initial overlay between two molecules and thus to obtain improved overlaps as
      judged by an increase in calculated similarity values. ReFlex3D is open-source
      and built as a python package working in combination with the OEChem Toolkit. As
      such it can readily be implemented in existing workflows ranging from the
      selection of compounds from a virtual screening campaign to the construction of
      similarity based prediction models to estimate binding affinities. We evaluate
      ReFlex3D against the AstraZeneca Validation Test Set and illustrate its potential
      within a predictive model compared to an established method (Posit).

PMID- 29600851
TI  - Octahedral-Tetrahedral Systems [Co( dppm O, O)3]2+[CoX4]2- Showing Slow Magnetic
      Relaxation with Two Relaxation Modes.
AB  - Three compounds with octahedral-tetrahedral Co(II) moieties of [Co( dppm O,
      O)3][CoX4] type, where X = SCN (1), Cl (2), or I (4) have been synthesized and
      characterized by the X-ray structure analysis (1 and 4), and spectroscopic
      methods. The dc magnetic measurements show high magnetic anisotropy for
      octahedral centers whereas tetrahedral sites possess moderate D values. These
      results are confirmed by the ab initio calculations. The ac susceptibility data
      reveals a slow magnetic relaxation for 2 and 4, similar to that of the X = Br
      analogue (3), whereas 1 displays no ac-absorption signal. There are two
      relaxation channels; the slower for 2 (4) possesses a relaxation time as long as
      tauLF= 178 (588) ms at T = 1.9 K and Bdc = 0.7 T. Also, the half-Zn analogue,
      [Co( dppm O, O)3][ZnI4], shows slow magnetic relaxation with two relaxation
      channels conditioned by the cationic unit [Co( dppm O, O)3]2+.

PMID- 29600853
TI  - Synthesis of Trifluoroethyl Pyrazolines via Trichloroisocyanuric Acid Promoted
      Cascade Cyclization/Trifluoromethylation of beta,gamma-Unsaturated Hydrazones.
AB  - A novel and efficient protocol for the construction of trifluoroethyl pyrazolines
      has been developed by cascade cyclization/trifluoromethylation reaction of
      beta,gamma-unsaturated hydrazones. This strategy uses cheap and commercially
      available trichloroisocyanuric acid as promoter and TMSCF3 as the
      trifluoromethylating reagent, which make the trifluoromethylating process much
      cheaper. A wide range of substrates can be applied in this process to afford the
      trifluoroethyl pyrazolines in good yield.

PMID- 29600854
TI  - Ammonium Iron(II,III) Phosphate:  Hydrothermal Synthesis and Characterization of
      NH4Fe2(PO4)2.
AB  - The mixed-valence iron phosphate NH4Fe2(PO4)2, which was synthesized by the high
      temperature, high-pressure hydrothermal method, crystallizes in the monoclinic
      space group C2/c with a = 20.0066(1) A, b = 14.8319(2) A, c = 9.9899(1) A, beta =
      119.278(1) degrees , and Z = 16. Its compact structure consists of chains of edge
      sharing FeIIO6 octahedra and chains of corner-sharing FeIIIO6 octahedra and PO4
      tetrahedra. These chains are connected to each other and delimit tunnels in the
      [221], [221], and [001] directions, in which NH4+ cations are located. Mossbauer
      spectroscopy confirms the presence of FeII and FeIII. The title compound is the
      first example of a mixed-valence ammonium iron phosphate.

PMID- 29600855
TI  - Rational Engineering of Multiple Active Sites in an Ester Hydrolase.
AB  - Effects of altering the properties of an active site in an enzymatic homogeneous
      catalyst have been extensively reported. However, the possibility of increasing
      the number of such sites, as commonly done in heterogeneous catalytic materials,
      remains unexplored, particularly because those have to accommodate appropriate
      residues in specific configurations. This possibility was investigated by using a
      serine ester hydrolase as the target enzyme. By using the Protein Energy
      Landscape Exploration software, which maps ligand diffusion and binding, we found
      a potential binding pocket capable of holding an extra catalytic triad and
      oxyanion hole contacts. By introducing two mutations, this binding pocket became
      a catalytic site. Its substrate specificity, substrate preference, and catalytic
      activity were different from those of the native site of the wild type ester
      hydrolase and other hydrolases, due to the differences in the active site
      architecture. Converting the binding pocket into an extra catalytic active site
      was proven to be a successful approach to create a serine ester hydrolase with
      two functional reactive groups. Our results illustrate the accuracy and
      predictive nature of modern modeling techniques, opening novel catalytic
      opportunities coming from the presence of different catalytic environments in
      single enzymes.

PMID- 29600856
TI  - Mechanism of Water Oxidation Catalyzed by a Mononuclear Iron Complex with a
      Square Polypyridine Ligand: A DFT Study.
AB  - The mononuclear [Cl-FeIII(dpa)-Cl]+ (1Cl) complex containing a square planar
      tetradentate polypyridine ligand has been reported to catalyze water oxidation in
      pH = 1 aqueous medium with ceric ammonium nitrate (CAN) as a chemical oxidant.
      The reaction mechanism of the oxygen evolution driven by this catalyst was
      investigated by means of density functional calculations. The results showed that
      one chloride ligand of 1Cl has to exchange with a water molecule to generate 1,
      [Cl-FeIII(dpa)-OH2]2+, as the starting species of the catalytic cycle. The
      initial one-electron oxidation of 1 is coupled with the release of two protons,
      generating [Cl-FeIV(dpa)?O]+ (2). Another one-electron transfer from 2 leads to
      the formation of an FeV?O complex [Cl-FeV(dpa)?O]2+ (3), which triggers the
      critical O-O bond formation. The electronic structure of 3 was found to be very
      similar to that of the high-valent heme-iron center of P450 enzymes, termed
      Compound I, in which a pi-cation radical ligand is believed to support a formal
      iron(IV)-oxo core. More importantly, 3 and Compound I share the same tendency
      toward electrophilic reactions. Two competing pathways were suggested for the O-O
      bond formation based on the present calculations. One is the nitrate nucleophilic
      attack on the iron(V)-oxo moiety with a total barrier of 12.3 kcal mol-1. In this
      case, nitrate functions as a co-catalyst for the dioxygen formation. The other is
      the water nucleophilic attack on iron(V)-oxo with a greater barrier of 16.5 kcal
      mol-1. In addition, ligand degradation via methyl hydrogen abstraction was found
      to have a barrier similar to that of the O-O bond formation, while the aromatic
      carbon hydroxylation has a higher barrier.

PMID- 29600857
TI  - From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and
      Beyond.
AB  - Coding for proteins has been considered the main function of RNA since the
      "central dogma" of biology was proposed. The discovery of noncoding transcripts
      shed light on additional roles of RNA, ranging from the support of polypeptide
      synthesis, to the assembly of subnuclear structures, to gene expression
      modulation. Cellular RNA has therefore been recognized as a central player in
      often unanticipated biological processes, including genomic stability. This ever
      expanding list of functions inspired us to think of RNA as a "smart" phone, which
      has replaced the older obsolete "cellular" phone. In this review, we summarize
      the last two decades of advances in research on the interface between RNA biology
      and genome stability. We start with an account of the emergence of noncoding RNA,
      and then we discuss the involvement of RNA in DNA damage signaling and repair,
      telomere maintenance, and genomic rearrangements. We continue with the depiction
      of single-molecule RNA detection techniques, and we conclude by illustrating the
      possibilities of RNA modulation in hopes of creating or improving new therapies.
      The widespread biological functions of RNA have made this molecule a reoccurring
      theme in basic and translational research, warranting it the transcendence from
      classically studied "cellular" RNA to "smart" RNA.

PMID- 29600858
TI  - Imaging the Dynamics of CH2BrI Photodissociation in the Near Ultraviolet Region.
AB  - The photodissociation dynamics of jet-cooled CH2BrI were investigated in the near
      ultraviolet (UV) region from 280-310 nm using velocity map imaging. We report the
      translational and internal energy distributions of the CH2Br radical and ground
      state I (2 P3/2) or spin-orbit excited I (2 P1/2) fragments determined by
      velocity map imaging of the ionized iodine fragments following 2 + 1 resonance
      enhanced multiphoton ionization of the nascent neutral iodine products. The
      velocity distributions indicate that most of the available energy is partitioned
      into the internal energy of the CH2Br radical with only modest translational
      excitation imparted to the cofragments, which is consistent with a simple
      impulsive model. Furthermore, from extrapolation of the velocity distribution
      results, the first determination of the C-I bond dissociation energy of CH2BrI is
      presented in this work to be D0 = 16 790 +/- 590 cm-1. The ion images appear
      anisotropic, indicative of a prompt dissociation, and the derived anisotropy
      parameters are consistently positive. Additionally, the angular distributions
      report on the electronic excited state dynamics, which validate recent works
      characterizing the electronic states responsible for the first absorption band of
      CH2BrI. In the current work, photolysis of CH2BrI on the red edge of the
      absorption spectrum reveals an additional channel producing I (2 P3/2) fragments.

PMID- 29600859
TI  - Copper(I)-Catalyzed Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from
      Azidoformates and Aryl Terminal Alkynes.
AB  - The copper(I)-catalyzed azide-alkyne cycloaddition reaction has been extensively
      studied and widely applied in organic synthesis. However, the formation of 1,2,3
      triazoles with electron-deficient azide has been a challenging problem. In this
      report, we have demonstrated the formation of regioselective 1,4-disubstituted
      1,2,3-triazoles from various types of aryl terminal alkynes and azidoformates,
      which are electron-deficient azides, using a commercialized [Cu(CH3CN)4]PF6
      copper(I) catalyst under mild conditions.

PMID- 29600860
TI  - Visible-Light-Promoted Oxidative Amidation of Bromoalkynes with Anilines: An
      Approach to alpha-Ketoamides.
AB  - A convenient and practical synthetic route to alpha-ketoamides from bromoalkynes
      and anilines through phototriggered organic transformations via a C-N cross
      coupling and an oxidation of C=C was developed. The reaction could be furnished
      without an external photocatalyst at ambient conditions, and a wide range of
      alpha-ketoamides were obtained in good yields.

PMID- 29600861
TI  - Transition-Metal-Free Cleavage of C-C Triple Bonds in Aromatic Alkynes with S8
      and Amides Leading to Aryl Thioamides.
AB  - A novel transition-metal-free cleavage reaction of C-C triple bonds in aromatic
      alkynes with S8 and amides furnishes aryl thioamides in moderate to excellent
      yields. The remarkable features of this thioamidation include the metal-free
      cleavage of C-C triple bond, mild reaction conditions, as well as wide substrate
      scope that is particularly compatible with some internal aromatic alkynes and
      acetamides.

PMID- 29600862
TI  - From Saddle-Shaped to Planar Cyclic Oligothienoacenes: Stepped-Cyclization and
      Their Applications in OFETs.
AB  - A series of cyclic oligothienoacenes (1, 3, and 4) have been successfully
      synthesized through a stepped-cyclization synthetic strategy from tetra[3,4
      thienylene] (2). Single-crystal X-ray diffraction analysis combined with
      theoretical calculations elucidated that the molecular configuration transforms
      from the saddle shape of 2 to the quasi-saddle shape (3b, 3c), then to the quasi
      helical shape (4b), and at last to the quasi-plane shape (1, 3a, 4a). Organic
      field-effect transistors (OFETs) based on 1, 3a, and 4a were fabricated. The
      field-effect mobilities of 7.5 * 10-4, 2.6 * 10-3, and 6.8 * 10-4 cm2 V-1 s-1
      were obtained for 1, 3a, and 4a, respectively. Compounds 3a and 4a can act as air
      stable p-type organic semiconductors, while 1 is sensitive to the air.

PMID- 29600863
TI  - Palladium-Catalyzed Hydrocarbonylative C-N Coupling of Alkenes with Amides.
AB  - An efficient palladium-catalyzed hydrocarbonylative C-N coupling of alkenes with
      amides has been developed. The reaction was performed via hydrocarbonylation of
      alkenes, followed by acyl metathesis with amides. Both intermolecular and
      intramolecular reactions proceed smoothly to give either branched or linear
      amides in high turnover number (3500) with NH4Cl or NMP.HCl as a proton source
      under the palladium catalysis. This reaction offers a catalytic convenient
      approach to deuterated amides when inexpensive NMP.DCl served as a deuterium
      source.

PMID- 29600864
TI  - Carbocation Lewis Acid Catalyzed Diels-Alder Reactions of Anthracene Derivatives.
AB  - The carbocation salt [Ph3C][BArF] has been identified as a viable Lewis acid
      catalyst for the Diels-Alder reactions between anthracene derivatives and
      unsaturated carbonyl compounds with good selectivity and high efficiency.

PMID- 29600865
TI  - Tailoring Polyethers for Post-polymerization Functionalization by Cross
      Metathesis.
AB  - Olefin cross metathesis is reported for the first time to attach small molecules
      to a range of novel polyethers with a poly(ethylene glycol) backbone and pendent
      alkene groups, allowing for a loading of up to one compound per monomer unit.
      These polymers are tailored to prevent the occurrence of self metathesis
      (reaction of the polymer with itself) by varying the substitution on the pendent
      alkenes, thus steering their reactivity toward olefin cross metathesis. Efficient
      functionalization has been observed for a range of coupling partners as a proof
      of concept for the use of olefin metathesis to graft small and larger molecules
      to polyethers for drug delivery. This approach also paves the way for the use of
      olefin cross metathesis as an efficient method to functionalize a wide variety of
      polymers with pendent olefin groups.

PMID- 29600866
TI  - Management of Technical Complications During Full-Mouth Implant Rehabilitation
      With Hybrid Prostheses Over a 7-Year Period.
AB  - Monolithic ceramics have been introduced in dentistry to help reduce technical
      complications reported with implant-supported metal-resin hybrid prostheses. This
      clinical report describes the maintenance and technical complications that
      occurred during a full-mouth implant rehabilitation using different prosthetic
      materials over a 7-year period. During the course of 4 of those years, multiple
      technical complications were encountered with the metal-resin hybrid prostheses,
      prompting the need for increased maintenance.New prostheses were inserted with
      screw-retained titanium frameworks and individually cemented single crowns, and
      subsequently no technical complications were encountered after 2 years of follow
      up.

PMID- 29600867
TI  - Minimally Invasive Ceramic Restorations: A Step-by-Step Clinical Approach.
AB  - Minimally invasive treatments are a dominant trend in dentistry. Due to the
      evolution of adhesive materials and ceramics, minimalistic ceramic restorations
      have been proposed as alternative treatment options to avoid unnecessary tooth
      reduction. The aim of this article is to show a clinical protocol for the correct
      diagnosis, treatment planning, and execution of minimally invasive ceramic
      veneers. Requiring only slight tooth preparation, this conservative technique is
      well-suited for restoration of teeth that need color and shape modification. The
      present clinical case demonstrates immediate success in restoring patient
      esthetics, function, and, in turn, self-esteem. After 2.5 years all veneers were
      still in exceptional condition and periodontal tissue was healthy. Minimally
      invasive ceramic restoration is shown to be an excellent option for conservative
      restorative treatment.

PMID- 29600868
TI  - Smear Layer Removal Efficacy Using EndoActivator and EndoUltra Activation
      Systems: An Ex Vivo SEM Analysis.
AB  - OBJECTIVE: This study evaluated intracanal smear layer removal using syringe and
      needle irrigation (ie, conventional irrigation [CI]) with and without adjunctive
      activation using EndoActivator(r) or EndoUltra(r). MATERIALS AND METHODS: Thirty
      five premolars were divided into three experimental groups (n = 10) and a control
      (n = 5): (1) CI, (2) CI plus sonic activation (EndoActivator), (3) CI plus
      ultrasonic activation (EndoUltra), or (4) CI using saline. All teeth were
      prepared to a size #40 K file. Following irrigation, the teeth were split and
      imaged using scanning electron microscopy (SEM). SEM images were evaluated by:
      (1) blinded researchers who provided a smear layer score (1-5), and (2) a custom
      software algorithm that automatically and independently quantified the number of
      open tubules. RESULTS: Use of both the EndoActivator and EndoUltra resulted in
      significantly cleaner smear layer scores at all canal thirds compared to CI (P <
      .001). The EndoUltra yielded significantly cleaner scores than the EndoActivator
      at the apical third (P < .001); however, no significant difference was evident in
      the middle and coronal thirds. The software analysis yielded the same conclusions
      as the smear layer scores except statistical significance was seen between the
      EndoUltra and EndoActivator at all canal thirds (P < .02). Of the adjunctive
      irrigant activators, the EndoUltra opened 94%, 117%, and 26% more tubules in the
      apex, middle, and coronal thirds, respectively, than the EndoActivator.
      CONCLUSIONS: The EndoUltra cleaned canals more effectively than the EndoActivator
      and CI.

PMID- 29600869
TI  - Periodontal Tissue Bioengineering: Is the Future Now?
AB  - Periodontitis affects nearly half of the adult population in the United States
      and leads to periodontium destruction, tooth loss, and tooth mobility. Novel
      bioengineering has become an area of interest in dentistry, as various approaches
      aim to regenerate attachment apparatus around diseased teeth with the use of
      barriers, scaffolds, bone grafts, or biologics. This article emphasizes recent
      findings in the fields of stem cell/gene therapy, 3-dimensional printing, and
      innovative scaffold designs for future applications in clinical care.

PMID- 29600870
TI  - Integrating Caries Management by Risk Assessment (CAMBRA) and Prevention
      Strategies Into the Contemporary Dental Practice.
AB  - In the past, the dental profession has adhered to a rigid tenet: remove decay
      from a tooth and then restore, a mindset that has been proverbially dubbed as
      "drill and fill." Today, dental caries is recognized as an infectious disease
      that affects children and adults throughout life. The philosophy of CAries
      Management By Risk Assessment, or CAMBRA(r), represents a paradigm shift. The
      CAMBRA concept provides the dentist with scientific, evidence-based solutions
      with which to approach treatment of dental caries disease. This article reviews
      the current understanding of the caries balance, the process of demineralization
      and remineralization of tooth structure, caries risk assessment, and the
      different levels of caries risk. Adequate treatment protocols specifically
      related to the remineralization of non-cavitated lesions and CAMBRA validation
      studies are discussed.

PMID- 29600871
TI  - Treatment of a Gingival Injury From a Cosmetic Laser Burn: A Case Report.
AB  - Gingival depigmentation is a periodontal plastic surgery procedure for the
      removal of pigmented gingiva. A gingival depigmentation procedure can be
      accomplished with the use of a laser; however, as described in this case report,
      laser burns can be associated with such a procedure, and if one occurs it must be
      subsequently managed. In this case, the patient presented with a large elliptical
      ulceration at the right maxillary premolar region. The underlying alveolar bone
      was exposed and the surrounding gingival margins were inflamed. After debridement
      of the area and removal of sequestrated bone, a bone graft and subepithelial
      connective tissue graft were placed using a microsurgery technique to correct the
      defect. This case report is intended to raise awareness regarding the potential
      complications of laser gingival depigmentation and present a possible treatment
      approach for such complications.

PMID- 29600872
TI  - Treatment of Oral Mucosal Lesions Associated With Overlapping Psychodermatologic
      Disorders.
AB  - Delusional infestations are psychodermatologic disorders in which those affected
      have a false belief they are infested by parasites and/or "growing" inanimate
      objects from cutaneous surfaces. Individuals with delusional parasitosis (DP)
      believe parasites, bacteria, worms, mites, or other living organisms are the
      source of cutaneous symptoms, while those with Morgellons disease (MD) attribute
      their symptoms to growth of small fibers or inorganic material. In both DP and
      MD, self-inflicted, non-healing cutaneous lesions caused by scratching at the
      affected areas to alleviate symptoms are commonly observed. This report describes
      a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of
      DP and MD. It is important for oral healthcare providers to recognize oral signs
      and symptoms that may be associated with psychodermatologic disorders.

PMID- 29600873
TI  - Long-Term Esthetic and Functional Success Following an Initial Treatment
      Complication.
AB  - This case describes the successful long-term outcome of a patient's treatment
      after a restorative failure occurred soon after delivery. The esthetic and
      restorative treatment has been successful for nearly a decade due largely to a
      careful, objective evaluation of all possible causes of the restorative failure.
      The treatment plan for the patient, who was assessed as high risk biomechanically
      and functionally, was carried out in the following phases: (1) an implant
      placement that required an osteotome sinus lift; (2) placement of feldspathic
      bonded veneers for the maxillary anterior teeth to minimize removal of tooth
      structure; (3) numerous core-supported restorations, with fixed partial dentures
      placed for teeth Nos. 19 through 21 and 28 through 30; and (4) the use of a Kois
      deprogrammerTM to determine condylar position/centric relation reference.
      Finally, the maxillary teeth were lengthened to create a pleasing smile and the
      vertical dimension increased and restored in centric relation.

PMID- 29600874
TI  - Innovations in Local Anesthesia are Easing the Pain of Dentistry.

PMID- 29600876
TI  - Swimming for dementia: An exploratory qualitative study (innovative practice).
AB  - Swimming is a non-weight bearing form of exercise that can be enjoyable and
      promote physical fitness. This qualitative study investigated a local group
      established as part of a national dementia swimming initiative. Semi-structured
      interviews with people with dementia (N = 4), carers or companions (N = 4) and
      the organisers and facilitators of the group (N = 6) were analysed using thematic
      analysis. This revealed four main themes: (1) the pleasure of swimming and its
      benefits as a form of exercise and for building confidence and empowering
      participants, (2) the importance of insight and empathy in creating a safe and
      secure experience, (3) the impact of dementia and (4) how participants valued
      being part of a group 'all in the same boat'. 'Dementia friendly swimming'
      appears to be a valuable form of exercise, but it requires considerable
      preparation and support to make it happen.

PMID- 29600875
TI  - Venus' Spectral Signatures and the Potential for Life in the Clouds.
AB  - The lower cloud layer of Venus (47.5-50.5 km) is an exceptional target for
      exploration due to the favorable conditions for microbial life, including
      moderate temperatures and pressures (~60 degrees C and 1 atm), and the presence
      of micron-sized sulfuric acid aerosols. Nearly a century after the ultraviolet
      (UV) contrasts of Venus' cloud layer were discovered with Earth-based
      photographs, the substances and mechanisms responsible for the changes in Venus'
      contrasts and albedo are still unknown. While current models include sulfur
      dioxide and iron chloride as the UV absorbers, the temporal and spatial changes
      in contrasts, and albedo, between 330 and 500 nm, remain to be fully explained.
      Within this context, we present a discussion regarding the potential for
      microorganisms to survive in Venus' lower clouds and contribute to the observed
      bulk spectra. In this article, we provide an overview of relevant Venus
      observations, compare the spectral and physical properties of Venus' clouds to
      terrestrial biological materials, review the potential for an iron- and sulfur
      centered metabolism in the clouds, discuss conceivable mechanisms of transport
      from the surface toward a more habitable zone in the clouds, and identify
      spectral and biological experiments that could measure the habitability of Venus'
      clouds and terrestrial analogues. Together, our lines of reasoning suggest that
      particles in Venus' lower clouds contain sufficient mass balance to harbor
      microorganisms, water, and solutes, and potentially sufficient biomass to be
      detected by optical methods. As such, the comparisons presented in this article
      warrant further investigations into the prospect of biosignatures in Venus'
      clouds.

PMID- 29600878
TI  - Quality improvement of spreadable processed cheese made from ultrafiltered milk
      retentates using commercial starter cultures.
AB  - This study was undertaken to evaluate the feasibility of using commercial starter
      cultures for quality improvement of spreadable processed cheese manufactured from
      ultrafiltered milk retentates. Compared to control, six samples of ultrafiltered
      milk retentate were incubated at 25 C with starter cultures CHN-22, FRC-60, and
      ABT-8. Three samples were incubated for 24 h and the others were incubated for 72
      h. Physicochemical, microbiological, and organoleptic characteristics in all
      treatments during the 90-day cold storage (6 +/- 2 C) period were determined. The
      results showed that protein content of all treatments was significantly lower
      than the control. Utilization of starter cultures in ultrafiltered processed
      cheese production increased titratable acidity, where titratable acidity of the
      treatments (PC22-3, PC60-3, and PC8-3) was significantly higher than the other
      treatments and the control. PC8-1, PC60-1, and PC22-1 treatments were the highest
      penetrometer readings and with low firmness. All treatments had higher water
      soluble nitrogen/total nitrogen%, total bacterial viable and lactic acid
      bacterial counts especially PC22-3, PC60-3, and PC8-3 compared to the control.
      The results revealed that PC60-1 and PC22-3 treatments gained the highest
      acceptability scores than PC60-3, PC22-1, and the control.

PMID- 29600877
TI  - Interference Assessment of Various Endogenous and Exogenous Substances on the
      Performance of the Eversense Long-Term Implantable Continuous Glucose Monitoring
      System.
AB  - BACKGROUND: A variety of prescriptions and over-the-counter medications interfere
      with transcutaneous continuous glucose monitoring (CGM) sensors. This study
      characterized the interference profile of the Eversense(r) CGM System
      (Senseonics, Inc., Germantown, MD), which has a different mechanism of glucose
      detection than other CGM systems. MATERIALS AND METHODS: Sensor bias (sensor
      glucose concentration measurement - plasma glucose concentration measured by a
      reference test) was measured in vitro against 41 different substances at
      supratherapeutic/supraphysiologic plasma concentrations. Testing was performed
      using a paired-sample method adapted from the Clinical and Laboratory Standards
      Institute guidance document EP7-A2. Any substance producing sensor bias that
      exceeded the International Organization for Standardization (ISO) document
      15197:2013 limits was then tested using an in vitro dose-response method to
      determine whether the concentration producing a significant sensor bias was
      within physiologic/therapeutic concentration ranges. RESULTS: Eight of 41
      substances produced a sensor bias that exceeded ISO 15197:2013 limits when tested
      in vitro at supratherapeutic/supraphysiologic plasma concentrations. Only two of
      these substances (tetracycline and mannitol) exceeded bias limits within
      therapeutic concentration ranges. Notably, neither acetaminophen nor ascorbic
      acid, which are substances reported to interfere with other CGM systems, produced
      sensor bias that exceeded ISO limits when used at physiologic concentrations.
      CONCLUSIONS: Although tetracycline and mannitol interfered with the Eversense
      sensor, substances frequently reported to interfere with enzymatic,
      electrochemical-based transcutaneous CGM systems, such as acetaminophen and
      ascorbic acid, did not affect Eversense readings.

PMID- 29600879
TI  - Textural and physical properties of retort processed rice noodles: Influence of
      chilling and partial substitution of rice flour with pregelatinized high-amylose
      maize starch.
AB  - This study investigated the influence of pregelatinized high-amylose maize starch
      and chilling treatment on the physical and textural properties of canned rice
      noodles thermally processed in a retort. Rice noodles were prepared from rice
      flour partially substituted with pregelatinized high-amylose maize starch (Hylon
      VIITM) in the ratios 0, 5, 10, and 15% (wt/wt). High-amylose maize starch
      improved the texture and brightness of fresh (not retorted) noodles. Chilling
      treatment led to significant (P <= 0.05) improvement in the texture of fresh
      noodles at all levels of substitution with high-amylose starch. The highest
      hardness was recorded at 15% amylose level in chilled nonretorted noodles. Retort
      processing induced a major loss of quality through water absorption, retort
      cooking loss, decreased noodle hardness, and lightness. However, the results
      showed that amylose and chilling treatment positively reduced the impact of
      retorting. For each level of amylose substitution, a low retort cooking loss and
      increased noodle hardness were associated with a chilling treatment. For both
      chilled and nonchilled noodles, retort cooking loss and hardness increased with
      increasing levels of amylose substitution.

PMID- 29600880
TI  - Pharmacotherapeutic strategies for treating hypertension in patients with
      obesity.
AB  - INTRODUCTION: Hypertension and obesity are important health challenges that
      independently increase cardiovascular morbidity and mortality. There is a lack of
      randomized controlled trials to clearly inform on preferred drug choices to be
      adopted in clinical practice for the treatment of obesity-related hypertension
      (OHT). Adequate differentiation of drug classes for preferential use in obesity
      or the metabolic syndrome aimed at avoiding adverse effects on body weight and
      the metabolic profile is neglected in this population, at least in part due to
      the lack of specific pharmacologic recommendations in hypertension guidelines.
      Areas covered: The authors summarize and suggest pharmacotherapeutic strategies
      based on pathophysiologic rationale to achieve blood pressure (BP) control and
      avoid adverse metabolic consequences in OHT. Expert opinion: Combinations of
      various pharmacologic antihypertensive approaches are required in the management
      of OHT. It is recommended that targeting sympathetic overactivity with a
      centrally acting sympatholytic agent such as moxonidine should be considered as a
      preferred second line treatment choice in combination with renin angiotensin
      system (RAS) blockade, the current first line choice. Though not all obese
      subjects have sympathetic overdrive, this approach is likely to provide effective
      control of blood pressure and improve the metabolic profile of patients with OHT
      along with positive implications for cardiovascular risk reduction.

PMID- 29600881
TI  - Mental health consequences of weight cycling in the first-year post-treatment for
      breast cancer.
AB  - OBJECTIVES: Weight cycling is linked with advanced breast cancer diagnosis,
      increased risk of cancer reoccurrence and cancer-related mortality. While women
      treated for breast cancer report challenges with navigating their post-treatment
      body shape and weight, the effects of weight cycling on body image and mental
      health have not been elucidated. This study examined associations between weight
      changes and weight cycling on psychological health (i.e. weight-related guilt,
      shame and depressive symptoms) among women in the first-year post-treatment.
      DESIGN AND OUTCOME MEASURES: Self-reported assessments of pre-cancer weight
      cycling, post-treatment weight-related guilt, shame and depressive symptoms, and
      objective assessments of weight were assessed in a longitudinal sample of 173
      women treated for breast cancer (Mage = 55.01 +/- 10.96 years). RESULTS: Based on
      findings from multilevel models, women experienced the most weight-related shame
      when their weight was heavier than their personal average. Additionally, heavier
      weight was associated with worse psychological health, particularly for women
      with a history of stable (vs. cycling) weight pre-cancer. CONCLUSIONS: Weight
      cycling pre-cancer and post-treatment weight change have important implications
      for psychological well-being. Due to the potential psychological consequences
      associated with a history of weight cycling, targeted strategies are needed to
      improve overall health outcomes for women's survivorship after breast cancer.

PMID- 29600882
TI  - Time to diagnosis in esophageal cancer: a cohort study.
AB  - BACKGROUND: The association between shorter time to diagnosis and favorable
      outcome is still unproven in esophageal cancer. This study aims to evaluate the
      effect of time to diagnosis on patient prognosis. MATERIAL AND METHODS:
      Retrospective cohort study of all 3613 symptomatic patients referred for
      esophageal cancer to our center from 1980 to 2011. Time to diagnosis was
      calculated as the number of days from first symptom onset to the diagnosis of
      esophageal cancer. The main outcome measures were: resectability and severe
      malnutrition at diagnosis; postoperative morbidity, mortality and survival.
      RESULTS: Longer time to diagnosis was significantly associated with severe
      malnutrition at diagnosis (odds ratio (OR): 1.003, 95% confidence interval
      (C.I.).: 1.001-1.006) but not with resectability (OR: 0.997, 95% C.I.: 0.994
      1.001). Longer time to diagnosis was not associated with postoperative morbidity
      (OR: 1.000, 95% C.I.: 0.998-1.003), postoperative mortality (OR: 1.002, 95% C.I.:
      0.998-1.006), five-year overall survival (hazard ratio (HR): 0.999, 95% C.I.:
      0.997-1.001) or five-year disease free survival (HR: 0.999, 95% C.I.: 0.998
      1.001). CONCLUSION: Longer time to diagnosis did not affect resectability,
      postoperative morbidity or survival. Further campaigns to raise awareness of
      cancer among population and primary health care providers may have limited effect
      on clinical outcome.

PMID- 29600883
TI  - Investigational drugs for vasospasm after subarachnoid hemorrhage.
AB  - INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) represents 3% of all
      strokes in the US. When the patient survives it can lead to permanent incapacity
      especially if the patient develops vasospasm. The vasospasm is a multifactorial
      disorder and can lead to delayed cerebral ischemia (DCI). Most of the drugs
      tested to treat vasospasm failed to improve outcome and the only exception is
      nimodipine. Areas covered: In this review, the authors describe the
      multifactorial process of vasospasm leading DCI after aSAH, discussing the
      treatments available based on the past and latest researches. Expert opinion:
      Nimodipine is the only FDA-approved medication with neuroprotective effect and
      able to improve outcomes after aSAH. Understanding nimodipine trials is mandatory
      to understand and criticize all the drug trials published until now. The
      mechanism to vasospasm is multifactorial and not completely understood and all
      the other attempts to find a better medication could not prove superior results.
      Newton and PEGylated Carboxyhemoglobin Bovine can be potentially effective to
      prevent vasospasm but we still need more data and large studies. Future research
      should investigate newer drugs, as well as the combination of multiple drugs
      therapy and the association with blood evacuation techniques.

PMID- 29600884
TI  - Surgical decompression for recurrent cord compression in cancer: a case series
      and review of the literature.
AB  - Spine metastases affect a significant number of cancer patients each year, with
      the spine being the third most common location for cancer spread. As patients
      live longer with improved treatments, the opportunity for recurrence at
      previously treated sites increases. Here, we describe seven patients with
      recurrent, compressive, metastatic spine tumors at previously surgically treated
      sites that required additional surgical intervention with manipulation of at
      least one rod. Five of the patients had recurrence including adjacent levels
      while two had recurrence solely at the previously decompressed level. The
      patients remained ambulatory for an average of 31.2 months after the initial
      surgery. We also discuss the role of adjuvant treatment in these patients and
      review the literature.

PMID- 29600885
TI  - Titanium dioxide nanoparticle exposure alters metabolic homeostasis in a cell
      culture model of the intestinal epithelium and Drosophila melanogaster.
AB  - Nanosized titanium dioxide (TiO2) is a common additive in food and cosmetic
      products. The goal of this study was to investigate if TiO2 nanoparticles affect
      intestinal epithelial tissues, normal intestinal function, or metabolic
      homeostasis using in vitro and in vivo methods. An in vitro model of intestinal
      epithelial tissue was created by seeding co-cultures of Caco-2 and HT29-MTX cells
      on a Transwell permeable support. These experiments were repeated with monolayers
      that had been cultured with the beneficial commensal bacteria Lactobacillus
      rhamnosus GG (L. rhamnosus). Glucose uptake and transport in the presence of TiO2
      nanoparticles was assessed using fluorescent glucose analog 2-(N-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG). When the cell monolayers were
      exposed to physiologically relevant doses of TiO2, a statistically significant
      reduction in glucose transport was observed. These differences in glucose
      absorption were eliminated in the presence of beneficial bacteria. The decrease
      in glucose absorption was caused by damage to intestinal microvilli, which
      decreased the surface area available for absorption. Damage to microvilli was
      ameliorated in the presence of L. rhamnosus. Complimentary studies in Drosophila
      melanogaster showed that TiO2 ingestion resulted in decreased body size and
      glucose content. The results suggest that TiO2 nanoparticles alter glucose
      transport across the intestinal epithelium, and that TiO2 nanoparticle ingestion
      may have physiological consequences.

PMID- 29600886
TI  - Updated incidence trends in cardia and non-cardia gastric adenocarcinoma in
      Sweden.
AB  - BACKGROUND: The aim of this study was to provide an update of the recent
      incidence trends of cardia and non-cardia gastric adenocarcinoma in Sweden.
      METHODS: Temporal trends in the age-standardised incidence were assessed
      separately for cardia and non-cardia gastric adenocarcinoma in 1970-2014 among
      all people in Sweden aged >=50 years. Data were retrieved from the Swedish Cancer
      Registry. The log-linear joinpoint regression method was used to identify change
      points in the incidence trends. The annual percent changes with 95% confidence
      intervals (CI) were calculated for each segment before and after change points.
      RESULTS: The overall incidence of cardia adenocarcinoma increased during the
      earlier period of 1970-1988, but was stable during the later period of 1989-2014
      (annual percent change: -0.3%, 95% CI: -0.7 to 0.2%). In contrast, in women aged
      50-69 years the incidence of cardia adenocarcinoma increased by 6.6% annually
      (95% CI: 1.9 to 11.5%) during the period 2005 to 2014. The incidence of non
      cardia gastric adenocarcinoma decreased by 4.4% per year (95% CI: -4.6 to -4.2%)
      in 1984-2014 and the decrease was stronger in men aged 70 years or older compared
      to other groups. CONCLUSION: The incidence of cardia adenocarcinoma is seemingly
      rapidly increasing in younger women, while it has been stable in other groups
      during recent years in Sweden. The incidence of non-cardia gastric adenocarcinoma
      continues to decrease, particularly in older men.

PMID- 29600887
TI  - Prognosis of dolichoectasia in non-cardioembolic transient ischemic attack and
      minor stroke.
AB  - Objectives This study aimed to estimate the prognosis of dolichoectasia in non
      cardioembolic transient ischemic attack (TIA) and minor stroke patients. Methods
      Data were derived from the imaging subgroup of patients in the Clopidogrel in
      High-risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial.
      Dolichoectasia was defined as ectasia (basilar artery diameter >4.5 mm) and
      dolichosis (either basilar artery bifurcation above the suprasellar cistern or
      lateral to the margin of the clivus or dorsum sellae). The prognosis included
      ischemic stroke recurrence and poor functional outcome (modified Rankin scale 2
      6) at 12-month follow-up. The association of dolichoectasia with risk factors and
      prognosis of patients were assessed using multivariable Cox regression models.
      Results Overall, 1089 patients with magnetic resonance images in the CHANCE trial
      were included in this subanalysis. A total of 98 (9.0%) patients were detected
      with dolichoectasia, and 106 (9.7%) patients had a recurrent ischemic stroke at
      12 months. Small artery occlusion (SAO) was more prevalent in patients with
      dolichoectasia compared with those without dolichoectasia (29.6% vs. 22.7%,
      hazard ratio [HR] 2.87, 95% confidence interval [CI] 1.59-5.17, p < 0.001).
      However, multivariate analysis showed no association of dolichoectasia with 12
      month recurrent stroke (9.2% vs. 9.8%, HR, 1.15; 95%CI, 0.32-4.12; p = 0.83) and
      poor functional outcome (7.6% vs. 8.4%, odds ratio, 1.22; 95%CI, 0.24-6.08; p =
      0.81) in the current subgroup analysis. Conclusions Dolichoectasia was
      significantly associated with SAO. There was no relationship between
      dolichoectasia and 12-month prognosis of patients with non-cardioembolic TIA or
      minor stroke.

PMID- 29600888
TI  - Genetic Variation of 'Candidatus Liberibacter solanacearum' Haplotype C and
      Identification of a Novel Haplotype from Trioza urticae and Stinging Nettle.
AB  - 'Candidatus Liberibacter solanacearum' (CLso) haplotype C is associated with
      disease in carrots and transmitted by the carrot psyllid Trioza apicalis. To
      identify possible other sources and vectors of this pathogen in Finland, samples
      were taken of wild plants within and near the carrot fields, the psyllids feeding
      on these plants, parsnips growing next to carrots, and carrot seeds. For
      analyzing the genotype of the CLso-positive samples, a multilocus sequence typing
      (MLST) scheme was developed. CLso haplotype C was detected in 11% of the T.
      anthrisci samples, in 35% of the Anthriscus sylvestris plants with discoloration,
      and in parsnips showing leaf discoloration. MLST revealed that the CLso in T.
      anthrisci and most A. sylvestris plants represent different strains than the
      bacteria found in T. apicalis and the cultivated plants. CLso haplotype D was
      detected in 2 of the 34 carrot seed lots tested, but was not detected in the
      plants grown from these seeds. Phylogenetic analysis by unweighted-pair group
      method with arithmetic means clustering suggested that haplotype D is more
      closely related to haplotype A than to C. A novel, sixth haplotype of CLso, most
      closely related to A and D, was found in the psyllid T. urticae and stinging
      nettle (Urtica dioica, Urticaceae), and named haplotype U.

PMID- 29600889
TI  - Transcranial direct current stimulation in the modulation of neuropathic pain: a
      systematic review.
AB  - Objective To investigate the neuromodulating effect of Transcranial Direct
      Current Stimulation (tDCS) on Neuropathic Pain (NP). Method A systematic review
      of articles published in the past five years in MEDLINE, LILACS, Cochrane,
      Scopus, ScienceDirect, and PEDro. The search was carried out from February to May
      2017 using the keywords: neuropathic pain, neuralgia, nerve pain, central pain,
      peripheral nerve pain, tDCS. The selected studies were full articles written in
      Portuguese, English, or Spanish with at least one control group, and no less than
      one pre- or post-intervention variable, with the exclusion of case studies or
      case series, animal model studies, and studies with combined therapy. The quality
      of the selected articles was evaluated through PEDro scale, whereas the level of
      agreement among reviewers was measured with the Cohen's kappa test, considering P
      < 0.05 to be significant. Results Eight articles were selected (PEDro: 8.5 +/-
      0.6; Cohen's kappa test: 0.703, P < 0.01), six of which were randomized
      controlled trials and two were controlled clinical trials. The following causes
      of NP were observed: spinal cord injury (SCI), amputation, stroke, multiple
      sclerosis (MS), and radiculopathy. All of the studies showed significant effects
      of tDCS on NP when compared to the control group, except for one with SCI and
      another related to radiculopathy. Discussion The shortage of good quality
      articles, the varying of ramp-on and ramp-off durations, and number of sessions,
      as well as the diversity of results found did not allow any definite conclusion
      on the efficacy of the neuromodulating effect of tDCS on NP.

PMID- 29600890
TI  - Preoperative brain temperature imaging on proton magnetic resonance spectroscopy
      predicts hemispheric ischemia during carotid endarterectomy for unilateral
      carotid stenosis with inadequate collateral blood flow.
AB  - Objective Preoperative magnetic resonance (MR) angiography sometimes shows the
      absence of collateral flow via the circle of Willis. This study examined whether
      brain temperature (BT) imaging on multi-voxel proton MR spectroscopy after this
      finding increases the accuracy of predicting hemispheric ischemia during internal
      carotid artery (ICA) clamping during endarterectomy for patients with symptomatic
      unilateral carotid stenosis. Methods In 52 patients with ICA stenosis (>=70%) and
      absence of collateral blood flow via the circle of Willis on preoperative MR
      angiography, BT imaging was displayed using proton multi-voxel MR spectroscopy.
      The difference between BTs in the affected and contralateral hemispheres
      (BTaffected hemisphere - BTcontralateral hemisphere) in the deep white matter of
      the centrum semiovale was calculated and defined as hemispheric DeltaBT.
      Development of cerebral hemispheric ischemia during ICA clamping was determined
      from intraoperative electroencephalography (EEG). Results Multivariate analysis
      revealed that high preoperative hemispheric DeltaBT was significantly associated
      with development of EEG-defined hemispheric ischemia (95% confidence intervals
      [CIs], 5.376-15.452; p = 0.006). The positive-predictive value for development of
      EEG-defined hemispheric ischemia was significantly greater for preoperative
      hemispheric DeltaBT following preoperative MR angiography (95%CI, 42-87%) than
      for preoperative MR angiography alone (95%CI, 13-37%). Conclusions For patients
      without collateral flow via the circle of Willis, BT imaging increases the
      predictive accuracy for development of hemispheric ischemia during ICA clamping
      during CEA.

PMID- 29600891
TI  - The effect of normobaric oxygen in patients with acute stroke: a systematic
      review and meta-analysis.
AB  - Background Normobaric oxygen (NBO) has received considerable attention due to
      controversial data in brain protection in patients with acute stroke. This study
      aims to analyze current data of NBO on brain protection as used in the clinic.
      Methods We searched for and reviewed relevant articles and references from
      Pubmed, Medline, Embase, Cochrane, and Clincialtrials.gov that were published
      prior to October 2017. Data from prospective studies were processed using
      RevMan5.0 software, provided by Cochrane collaboration and transformed using
      relevant formulas. Results A total of 11 prospective RCT studies including 6366
      patients with acute stroke (NBO group, 3207; control group, 3159) were enrolled
      in this analysis. ?NIHSS represented the values of NIHSS at 4, 24 h, or 7 days
      post-stroke minus baseline NIHSS. Compared to controls, there was a minor trend
      toward NBO benefits in short-term prognostic indices, as indicated by decreased
      DeltaNIHSS at our defined time points. By contrast, NBO decreased Barthel Index
      scores between 3 and 7 months, and increased death rates at 3, 6 months, and 1
      year, whereas, modified Rankin Scale scores between 3 and 6 months were
      unchanged. Conclusions The existing trends toward benefits revealed in this meta
      analysis help us appreciate the promising value of NBO, although current evidence
      of NBO on improving clinical outcomes of stroke is insufficient. Well-designed
      multi-center clinical trials are encouraged and urgently needed to further
      explore the efficacy of NBO on brain protection.

PMID- 29600892
TI  - The Long and the Short of It in Cystic Fibrosis Clinical Research Outcomes.

PMID- 29600893
TI  - Ambient Pollution Contributes Not Only to Pneumonia Cases but Also to Disease
      Severity.

PMID- 29600894
TI  - John C. Longhurst, MD, PhD (1947-2018): a pioneer in acupuncture hypertension
      research.

PMID- 29600895
TI  - Myocardial infarction remodeling that progresses to heart failure: a signaling
      misunderstanding.
AB  - After myocardial infarction, remodeling of the left ventricle involves a wound
      healing orchestra involving a variety of cell types. In order for wound healing
      to be optimal, appropriate communication must occur; these cells all need to come
      in at the right time, be activated at the right time in the right amount, and
      know when to exit at the right time. When this occurs, a new homeostasis is
      obtained within the infarct, such that infarct scar size and quality are
      sufficient to maintain left ventricular size and shape. The ideal scenario does
      not always occur in reality. Often, miscommunication can occur between infarct
      and remote spaces, across the temporal wound-healing spectrum, and across organs.
      When miscommunication occurs, adverse remodeling can progress to heart failure.
      This review discusses current knowledge gaps and recent development of the roles
      of inflammation and the extracellular matrix in myocardial infarction remodeling.
      In particular, the macrophage is one cell type that provides direct and indirect
      regulation of both the inflammatory and scar-forming responses. We summarize
      current research efforts focused on identifying biomarker indicators that reflect
      the status of each component of the wound-healing process to better predict
      outcomes.

PMID- 29600896
TI  - Wavelet decomposition analysis is a clinically relevant strategy to evaluate
      cerebrovascular buffering of blood pressure after spinal cord injury.
AB  - The capacity of the cerebrovasculature to buffer changes in blood pressure (BP)
      is crucial to prevent stroke, the incidence of which is three- to fourfold
      elevated after spinal cord injury (SCI). Disruption of descending sympathetic
      pathways within the spinal cord due to cervical SCI may result in impaired
      cerebrovascular buffering. Only linear analyses of cerebrovascular buffering of
      BP, such as transfer function, have been used in SCI research. This approach does
      not account for inherent nonlinearity and nonstationarity components of
      cerebrovascular regulation, often depends on perturbations of BP to increase the
      statistical power, and does not account for the influence of arterial CO2
      tension. Here, we used a nonlinear and nonstationary analysis approach termed
      wavelet decomposition analysis (WDA), which recently identified novel sympathetic
      influences on cerebrovascular buffering of BP occurring in the ultra-low
      frequency range (ULF; 0.02-0.03Hz). WDA does not require BP perturbations and can
      account for influences of CO2 tension. Supine resting beat-by-beat BP
      (Finometer), middle cerebral artery blood velocity (transcranial Doppler), and
      end-tidal CO2 tension were recorded in cervical SCI ( n = 14) and uninjured ( n =
      16) individuals. WDA revealed that cerebral blood flow more closely follows
      changes in BP in the ULF range ( P = 0.0021, Cohen's d = 0.89), which may be
      interpreted as an impairment in cerebrovascular buffering of BP. This persisted
      after accounting for CO2. Transfer function metrics were not different in the ULF
      range, but phase was reduced at 0.07-0.2 Hz ( P = 0.03, Cohen's d = 0.31).
      Sympathetically mediated cerebrovascular buffering of BP is impaired after SCI,
      and WDA is a powerful strategy for evaluating cerebrovascular buffering in
      clinical populations.

PMID- 29600897
TI  - Influence of myocardial oxygen demand on the coronary vascular response to
      arterial blood gas changes in humans.
AB  - It remains unclear if the human coronary vasculature is inherently sensitive to
      changes in arterial Po2 and Pco2 or if coronary vascular responses are the result
      of concomitant increases in myocardial O2 consumption/demand ([Formula: see
      text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would
      be attenuated in healthy men when [Formula: see text] was attenuated with beta1
      adrenergic receptor blockade. Healthy men (age: 25 +/- 1 yr, n = 11) received
      intravenous esmolol (beta1-adrenergic receptor antagonist) or volume-matched
      saline in a double-blind, randomized crossover study and were exposed to
      poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements
      made at baseline and after 5 min of steady state at each gas manipulation
      included left anterior descending coronary blood velocity (LADV; Doppler
      echocardiography), heart rate, and arterial blood pressure. LADV values at the
      end of each hypoxic condition were compared between esmolol and placebo. The rate
      pressure product (RPP) and left ventricular mechanical energy (MELV) were
      calculated as indexes of [Formula: see text]. All gas manipulations augmented
      RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after beta1
      adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV
      responses, beta1-adrenergic receptor blockade did not attenuate the mean LADV
      vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 +/
      2.2 vs. 27.3 +/- 1.6 cm/s) and isocapnic hypoxia (29.5 +/- 1.5 vs. 30.3 +/- 2.2
      cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was
      blocked by beta1-adrenergic receptor blockade. These results indicate a direct
      influence of arterial Po2 on coronary vascular regulation that is independent of
      [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an
      increase in epicardial coronary artery blood velocity. beta1-Adrenergic receptor
      blockade did not diminish the hypoxemic coronary response despite reduced
      myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood
      flow independent of myocardial O2 consumption. A plateau in the mean left
      anterior descending coronary artery blood velocity-rate-pressure product
      relationship suggested beta1-adrenergic receptor-mediated, feedforward epicardial
      coronary artery dilation. In addition, we observed a synergistic effect of Po2
      and Pco2 during hypercapnic hypoxia.

PMID- 29600898
TI  - Specific circulating microRNAs display dose-dependent responses to variable
      intensity and duration of endurance exercise.
AB  - Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control
      posttranscriptional gene expression, mediate processes that underlie phenotypical
      plasticity to exercise. The relationship and biological relevance between c-miRNA
      expression and variable dose exercise exposure remains uncertain. We hypothesized
      that certain c-miRNAs respond to changes in exercise intensity and/or duration in
      a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete
      intracellular stores, thus facilitating gene reprogramming and exercise
      adaptation. To address these hypotheses, healthy men participated in variable
      intensity ( n = 12, 30 * 1 min at 6, 7, and 8 miles/h, order randomized) and
      variable duration ( n = 14, 7 * 1 mile/h for 30, 60, and 90 min, order
      randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1
      and miRNA-133a) and others with known relevance to exercise were measured before
      and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive
      (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without
      dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with
      dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and
      miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low
      intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over
      4 wk. In high- but not low-intensity-trained mice, we found increased plasma c
      miR-133a along with decreased intracellular miRNA-133a and increased serum
      response factor, a known miR-133a target gene, in muscle. Characterization of c
      miRNAs that are dose responsive to exercise in humans and mice supports the
      notion that they directly mediate physiological adaptation to exercise,
      potentially through depletion of intracellular stores of muscle-specific miRNAs.
      NEW & NOTEWORTHY In this study of humans and mice, we define circulating
      microRNAs in plasma that are dose responsive to exercise. Our data support the
      notion that these microRNAs mediate physiological adaptation to exercise
      potentially through depletion of intracellular stores of muscle-specific
      microRNAs and releasing their inhibitory effects on target gene expression.

PMID- 29600900
TI  - Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than
      just a radical idea.
AB  - Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary
      insufficiency, exhibits potent cardiac and vascular protective properties.
      Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in
      response to stressors including reduced hepatic bilirubin excretion/increased red
      blood cell breakdown, with individuals usually informed by their clinician that
      their condition is of little consequence. However, GS appears to protect from all
      cause mortality, with progressively elevated total bilirubin associated with
      protection from ischemic heart and chronic obstructive pulmonary diseases.
      Bilirubin may protect against these diseases and associated mortality by reducing
      circulating cholesterol, oxidative lipid/protein modifications, and blood
      pressure. In addition, bilirubin inhibits platelet activation and protects the
      heart from ischemia-reperfusion injury. These effects attenuate multiple stages
      of the atherosclerotic process in addition to protecting the heart during
      resultant ischemic stress, likely underpinning the profound reduction in
      cardiovascular mortality in hyperbilirubinemic GS. This review outlines our
      current knowledge of and uses for bilirubin in clinical medicine and summarizes
      recent progress in revealing the physiological importance of this poorly
      understood molecule. We believe that this review will be of significant interest
      to clinicians, medical researchers, and individuals who have GS.

PMID- 29600899
TI  - Human muscle-specific A-kinase anchoring protein polymorphisms modulate the
      susceptibility to cardiovascular diseases by altering cAMP/PKA signaling.
AB  - One of the crucial cardiac signaling pathways is cAMP-mediated PKA signal
      transduction, which is regulated by a family of scaffolding proteins, i.e., A
      kinase anchoring proteins (AKAPs). Muscle-specific AKAP (mAKAP) partly regulates
      cardiac cAMP/PKA signaling by binding to PKA and phosphodiesterase 4D3 (PDE4D3),
      among other proteins, and plays a central role in modulating cardiac remodeling.
      Moreover, genetics plays an incomparable role in modifying the risk of
      cardiovascular diseases (CVDs). Single-nucleotide polymorphisms (SNPs) in various
      proteins have especially been shown to predispose individuals to CVDs. Hence, we
      hypothesized that human mAKAP polymorphisms found in humans with CVDs alter the
      cAMP/PKA pathway, influencing the susceptibility of individuals to CVDs. Our
      computational analyses revealed two mAKAP SNPs found in cardiac disease-related
      patients with the highest predicted deleterious effects, Ser 1653 Arg (S1653R)
      and Glu 2124 Gly (E2124G). Coimmunoprecipitation data in human embryonic kidney
      293T cells showed that the S1653R SNP, present in the PDE4D3-binding domain of
      mAKAP, changed the binding of PDE4D3 to mAKAP and that the E2124G SNP, flanking
      the 3'-PKA binding domain, changed the binding of PKA before and after
      stimulation with isoproterenol. These SNPs significantly altered intracellular
      cAMP levels, global PKA activity, and cytosolic PDE activity compared with the
      wild type before and after isoproterenol stimulation. PKA-mediated
      phosphorylation of pathological markers was found to be upregulated after cell
      stimulation in both mutants. In conclusion, human mAKAP polymorphisms may
      influence the propensity of developing CVDs by affecting cAMP/PKA signaling,
      supporting the clinical significance of PKA-mAKAP-PDE4D3 interactions. NEW &
      NOTEWORTHY We found that single-nucleotide polymorphisms in muscle-specific A
      kinase anchoring protein found in human patients with cardiovascular diseases
      significantly affect the cAMP/PKA signaling pathway. Our results showed, for the
      first time, that human muscle-specific A-kinase anchoring protein polymorphisms
      might alter the susceptibility of individuals to develop cardiovascular diseases
      with known underlying molecular mechanisms.

PMID- 29600902
TI  - April Highlights/Papers by Junior Investigators/NIH News.

PMID- 29600901
TI  - PDE8: A Novel Target in Airway Smooth Muscle.

PMID- 29600903
TI  - Editorial. Endoscopic endonasal surgery for pediatric craniopharyngiomas.

PMID- 29600904
TI  - A case of junctional neural tube defect associated with a lipoma of the filum
      terminale: a new subtype of junctional neural tube defect?
AB  - The embryological development of the central nervous system takes place during
      the neurulation process, which includes primary and secondary neurulation. A new
      form of dysraphism, named junctional neural tube defect (JNTD), was recently
      reported, with only 4 cases described in the literature. The authors report a
      fifth case of JNTD. This 5-year-old boy, who had been operated on during his 1st
      month of life for a uretero-rectal fistula, was referred for evaluation of
      possible spinal dysraphism. He had urinary incontinence, clubfeet, and a history
      of delayed walking ability. MRI showed a spinal cord divided in two, with an
      upper segment ending at the T-11 level and a lower segment at the L5-S1 level,
      with a thickened filum terminale. The JNTDs represent a recently classified
      dysraphism caused by an error during junctional neurulation. The authors suggest
      that their patient should be included in this category as the fifth case reported
      in the literature and note that this would be the first reported case of JNTD in
      association with a lipomatous filum terminale.

PMID- 29600905
TI  - Therapeutic outcomes of transsphenoidal surgery in pediatric patients with
      craniopharyngiomas: a single-center study.
AB  - OBJECTIVE The aim of this study was to analyze the outcomes of transsphenoidal
      surgery (TSS) in a single-center clinical series of pediatric craniopharyngioma
      patients treated with gross-total resection (GTR). METHODS The authors
      retrospectively reviewed the surgical outcomes for 65 consecutive patients with
      childhood craniopharyngiomas (28 girls and 37 boys, mean age 9.6 years) treated
      with TSS (45 primary and 20 repeat surgeries) between 1990 and 2015. Tumors were
      classified as subdiaphragmatic or supradiaphragmatic. Demographic and clinical
      characteristics, including extent of resection, complications, incidence of
      recurrence, pre- and postoperative visual disturbance, pituitary function, and
      incidence of diabetes insipidus (DI), as well as new-onset obesity, were analyzed
      and compared between the primary surgery and repeat surgery groups. RESULTS Of
      the 45 patients in the primary surgery group, 26 (58%) had subdiaphragmatic
      tumors and 19 had supradiaphragmatic tumors. Of the 20 patients in the repeat
      surgery group, 9 (45%) had subdiaphragmatic tumors and 11 had supradiaphragmatic
      tumors. The only statistically significant difference between the 2 surgical
      groups was in tumor size; tumors were larger (mean maximum diameter 30 mm) in the
      primary surgery group than in the repeat surgery group (25 mm) (p = 0.008). GTR
      was accomplished in 59 (91%) of the 65 cases; the GTR rate was higher in the
      primary surgery group than in the repeat surgery group (98% vs 75%, p = 0.009).
      Among the patients who underwent GTR, 12% experienced tumor recurrence, with a
      median follow-up of 7.8 years, and recurrence tended to occur less frequently in
      primary than in repeat surgery patients (7% vs 27%, p = 0.06). Of the 45 primary
      surgery patients, 80% had deteriorated pituitary function and 83% developed DI,
      whereas 100% of the repeat surgery patients developed these conditions. Among
      patients with preoperative visual disturbance, vision improved in 62% but
      worsened in 11%. Visual improvement was more frequent in primary than in repeat
      surgery patients (71% vs 47%, p < 0.001), whereas visual deterioration was less
      frequent following primary surgery than repeat surgery (4% vs 24%, p = 0.04).
      Among the 57 patients without preoperative obesity, new-onset postoperative
      obesity was found in 9% of primary surgery patients and 21% of repeat surgery
      patients (p = 0.34) despite aggressive resection, suggesting that hypothalamic
      dysfunction was rarely associated with GTR by TSS in this series. However,
      obesity was found in 25% of the repeat surgery patients preoperatively due to
      prior transcranial surgery. Although there were no perioperative deaths, there
      were complications in 12 cases (18%) (6 cases of CSF leaks, 3 cases of
      meningitis, 2 cases of transient memory disturbance, and 1 case of
      hydrocephalus). Postoperative CSF leakage appeared to be more common in repeat
      than in primary surgery patients (20% vs 4.4%, p = 0.2). CONCLUSIONS The results
      of TSS for pediatric craniopharyngioma in this case series suggest that GTR
      should be the goal for the first surgical attempt. GTR should be achievable
      without serious complications, although most patients require postoperative
      hormonal replacement. When GTR is not possible or tumor recurrence occurs after
      GTR, radiosurgery is recommended to prevent tumor regrowth or progression.

PMID- 29600906
TI  - Letter to the Editor. Can the ETVSS adequately predict success of repeat ETV?

PMID- 29600907
TI  - Posterior-approach single-level apical spinal osteotomy in pediatric patients for
      severe rigid kyphoscoliosis: long-term clinical and radiological outcomes.
AB  - OBJECTIVE Spinal osteotomy in pediatric patients is challenging due to various
      factors. For correction of severe rigid kyphoscoliosis in children, numerous
      techniques with anterior or posterior or combined approaches, as well as
      multilevel osteotomies, have been described. These techniques are associated with
      prolonged operative times and large amounts of blood loss. The purpose of this
      study was to evaluate the clinical and radiologically confirmed efficacy of a
      modification of the apical spinal osteotomy (ASO) technique-posterior-only single
      level asymmetric closing osteotomy-in pediatric patients with severe rigid
      kyphoscoliosis. METHODS The authors performed a retrospective study of a case
      series involving pediatric patients with severe spinal deformity operated on by a
      single surgeon at a single institution over a period of approximately 5 years.
      The inclusion criteria were age < 14 years, rigid thoracic/thoracolumbar/lumbar
      kyphosis (> 70 degrees ) with or without neurological deficit and with or without
      scoliosis, and a minimum of 2 years of follow-up. Patients with cervical or
      lumbosacral kyphoscoliosis were excluded from the study. Demographic and clinical
      parameters, including age, sex, etiology of kyphoscoliosis, neurological
      examination status (Frankel grade), and visual analog scale (VAS) and Oswestry
      Disability Index (ODI) scores, were noted. Operative parameters (level of
      osteotomy, number of levels fused, duration of surgery, blood loss, and
      complications) were also recorded. Radiological assessment was done for
      preoperative and postoperative kyphosis and scoliosis as well as the final Cobb
      angle. Similarly, sagittal vertical axis (SVA) correction was calculated. Fusion
      was assessed in all patients at the final follow-up evaluation. RESULTS A total
      of 26 pediatric patients (18 male and 8 female) with a mean age of 9 years met
      the inclusion criteria and had data available for analysis, and all of these
      patients had severe scoliosis as well as kyphosis. Comparison of preoperative and
      postoperative values showed a significant improvement (p < 0.05) in radiological,
      clinical, and functional parameters (Cobb angle for scoliosis and kyphosis, SVA,
      VAS, and ODI). With respect to kyphosis, the mean preoperative Cobb angle was
      96.54 degrees , the mean postoperative angle was 30.77 degrees , and the mean
      angle at final follow-up was 34.81 degrees  (average loss of correction of 4.23
      degrees ), for a final average correction of 64.15%. With respect to scoliosis,
      the mean preoperative angle was 52.54 degrees , the mean postoperative angle was
      15.77 degrees , and the mean angle at final follow-up was 19.42 degrees  (average
      loss of correction of 3.66 degrees ), for a final average correction of 60.95%.
      The preoperative SVA averaged 7.6 cm; the mean SVA improved to 3.94 cm at the end
      of 2 years. Bony fusion was achieved in all patients. The mean number of levels
      fused was 5.69. The mean operative time was 243.46 minutes, with an average
      intraoperative blood loss of 336.92 ml. Nonneurological complications occurred in
      15.39% of patients (2 dural tears, 1 superficial infection, 1 implant failure).
      At the 2-year follow-up, 25 of the 26 patients had maintained or improved their
      neurological status. One patient developed paraplegia immediately after the
      operation and recovered only partially. CONCLUSIONS Analysis of data from this
      series of 26 cases indicates that this posterior-approach single-level technique
      is effective for the correction of severe rigid kyphoscoliosis in pediatric
      patients, providing good clinical and radiological results in most cases.

PMID- 29600908
TI  - Pedicle screws with a thin hydroxyapatite coating for improving fixation at the
      bone-implant interface in the osteoporotic spine: experimental study in a porcine
      model.
AB  - OBJECTIVE Instrumentation failure caused by the loosening of pedicle screws (PSs)
      in patients with osteoporosis is a serious problem after spinal surgery. The
      addition of a thin hydroxyapatite (HA) surface coating applied by using a
      sputtering process was reported recently to be a promising method for providing
      bone conduction around an implant without a significant risk of coating-layer
      breakage. In this study, the authors evaluated the biomechanical and histological
      features of the bone-implant interface (BII) of PSs with a thin HA coating in an
      in vivo porcine osteoporotic spine model. METHODS Three types of PSs
      (untreated/standard [STPS], sandblasted [BLPS], and HA-coated [HAPS] PSs) were
      implanted into the thoracic and lumbar spine (T9-L6) of 8 mature Clawn miniature
      pigs (6 ovariectomized [osteoporosis group] and 2 sham-operated [control group]
      pigs). The spines were harvested from the osteoporosis group at 0, 2, 4, 8, 12,
      or 24 weeks after PS placement and from the control group at 0 or 24 weeks. Their
      bone mineral density (BMD) was measured by peripheral quantitative CT.
      Histological evaluation of the BIIs was conducted by performing bone
      volume/tissue volume and bone surface/implant surface measurements. The strength
      of the BII was evaluated with extraction torque testing. RESULTS The BMD
      decreased significantly in the osteoporosis group (p < 0.01). HAPSs exhibited the
      greatest mean extraction peak torque at 8 weeks, and HAPSs and BLPSs exhibited
      significantly greater mean torque than the STPSs at 12 weeks (p < 0.05). The bone
      surface/implant surface ratio was significantly higher for HAPSs than for STPSs
      after 2 weeks (p < 0.05), and bonding between bone and the implant surface was
      maintained until 24 weeks with no detachment of the coating layer. In contrast,
      the bone volume/tissue volume ratio was significantly higher for HAPSs than for
      BLPSs or STPSs only at 4 weeks. CONCLUSIONS Using PSs with a thin HA coating
      applied using a sputtering process strengthens bonding at the BII, which might
      improve early implant fixation after spinal surgery for osteoporosis. However,
      the absence of increased bone mass around the screw remains a concern;
      prescribing osteoporosis treatment to improve bone quality might be necessary to
      prevent fractures around the screws.

PMID- 29600909
TI  - Spontaneous occult intracranial hypotension precipitating life-threatening
      cerebral venous thrombosis: case report.
AB  - Spontaneous intracranial hypotension (SIH) is an uncommon headache etiology,
      typically attributable to an unprovoked occult spinal CSF leak. Although
      frequently benign, serious complications may occur, including cerebral venous
      thrombosis (CVT). The objective of this study was to examine a highly complicated
      case of CVT attributable to SIH as a lens for understanding the heterogeneous
      literature on this rare complication, and to provide useful, evidence-based,
      preliminary clinical recommendations. A 43-year-old man presented with 1 week of
      headache, dizziness, and nausea, which precipitously evolved to hemiplegia. CT
      venography confirmed CVT, and therapeutic heparin was initiated. He suffered a
      generalized seizure due to left parietal hemorrhage, which subsequently expanded.
      He developed signs of mass effect and herniation, heparin was discontinued, and
      he was taken to the operating room for clot evacuation and external ventricular
      drain placement. Intraoperatively, the dura was deflated, suggesting underlying
      SIH. Ventral T-1 CSF leak was identified, which failed multiple epidural blood
      patches and required primary repair. The patient ultimately made a complete
      recovery. Systematic review identified 29 publications describing 36 cases of SIH
      associated CVT. Among 31 patients for whom long-term neurological outcome was
      reported, 25 (81%) recovered completely. Underlying coagulopathy/risk factors
      were identified in 11 patients (31%). CVT is a rare and potentially lethal
      sequela occurring in 2% of SIH cases. Awareness of the condition is poor, risking
      morbid complications. Evaluation and treatment should be directed toward
      identification and treatment of occult CSF leaks. Encouragingly, good
      neurological outcomes can be achieved through vigilant multidisciplinary
      neurosurgical and neurocritical care.

PMID- 29600910
TI  - Retrospective single-surgeon study of 1123 consecutive cases of anterior cervical
      discectomy and fusion: a comparison of clinical outcome parameters, complication
      rates, and costs between outpatient and inpatient surgery groups, with a
      literature review.
AB  - OBJECTIVE Outpatient anterior cervical discectomy and fusion (ACDF) is becoming
      more common and has been reported to offer advantages over inpatient procedures,
      including reducing nosocomial infections and costs, as well as improving patient
      satisfaction. The goal of this retrospective study was to evaluate and compare
      outcome parameters, complication rates, and costs between inpatient and
      outpatient ACDF cases performed by 1 surgeon at a single institution. METHODS In
      a retrospective study, the records of all patients who had undergone first-time
      ACDF performed by a single surgeon in the period from June 1, 2003, to January
      31, 2016, were reviewed. Patients were categorized into 2 groups: those who had
      undergone ACDF as outpatients in a same-day surgical center and those who had
      undergone surgery in the hospital with a minimum 1-night stay. Outcomes for all
      patients were evaluated with respect to the following parameters: age, sex,
      length of stay, preoperative and postoperative pain (self-reported
      questionnaires), number of levels fused, fusion, and complications, as well as
      the presence of risk factors, such as an increased body mass index, smoking, and
      diabetes mellitus. RESULTS In total, 1123 patients were operated on, 485 (43%)
      men and 638 (57%) women, whose mean age was 50 years. The mean follow-up time was
      25 months. Overall, 40.5% underwent 1-level surgery, 34.3% 2-level, 21.9% 3
      level, and 3.2% 4-level. Only 5 patients had nonunion of vertebrae; thus, the
      fusion rate was 99.6%. Complications occurred in 40 patients (3.6%), with 9
      having significant complications (0.8%). Five hundred sixty patients (49.9%) had
      same-day surgery, and 563 patients (50.1%) stayed overnight in the hospital. The
      inpatients were older, were more commonly male, and had a higher rate of
      diabetes. Smoking status did not influence the length of stay. Both groups had a
      statistically significant reduction in pain (expressed as a visual analog scale
      score) postoperatively with no significant difference between the groups. One-
      and 2-level surgeries were done significantly more often in the outpatient
      setting (p < 0.001). The complication rate was 4.1% in the outpatient group and
      3.0% in the inpatient group; there was no statistically significant difference
      between the 2 groups (p = 0.339). Significantly more complications occurred with
      3- and 4-level surgeries than with 1- and 2-level procedures (p < 0.001, chi
      square test). The overall average inpatient cost for commercial insurance
      carriers was 26% higher than those for outpatient surgery. CONCLUSIONS Anterior
      cervical discectomy and fusion is safe for patients undergoing 1- or 2-level
      surgery, with a very significant rate of pain reduction and fusion and a low
      complication rate in both clinical settings. Outpatient and inpatient groups
      undergoing 3- or 4-level surgery had an increased risk of complications (compared
      with those undergoing 1- or 2-level surgery), with a negligible difference
      between the 2 groups. This finding suggests that these procedures can also be
      included as standard outpatient surgery. Comparable outcome parameters and the
      same complication rates between inpatient and outpatient groups support both
      operative environments.

PMID- 29600911
TI  - Intraoperative monitoring with visual evoked potentials for brain surgeries.
AB  - OBJECTIVE The goal of this study was to determine the performance of
      intraoperative visual evoked potentials (VEPs) in detecting visual field changes.
      METHODS Assessments of VEPs were performed with simultaneous retinal responses by
      using white light-emitting diodes protected from scialytic microscope lights. The
      alarm criterion was a reproducible decrease in amplitude of the VEP P100 wave of
      20% or more. Visual fields were assessed preoperatively and 1 month postsurgery
      (Goldmann perimetry). RESULTS The VEPs were analyzed for 29 patients undergoing
      resection of a brain lesion. In 89.7% of patients, steady VEP and retinal
      responses were obtained for monitoring. The absence of alarm was associated in
      94.4% of cases with the absence of postoperative visual changes (specificity).
      The alarms correctly identified 66.7% of cases with any postoperative changes and
      100% of cases with changes more severe than just a discrete quadrantanopia or
      deterioration of an existing quadrantanopia (sensitivity, new diffuse
      deterioration < 2 dB). In 11.5% of patients, a transitory VEP decrease with
      subsequent recovery was observed without postoperative defects. CONCLUSIONS
      Intraoperative VEPs were performed with simultaneous recording of
      electroretinograms, with protection from lights of the operating room and with
      white light-emitting diodes. Intraoperative VEPs were shown to be reliable in
      predicting postoperative visual field changes. In this series of intraaxial brain
      procedures, reliable intraoperative VEP monitoring was achieved, allowing at
      minimum the detection of new quadrantanopia. The standardization of this
      technique appears to be a valuable effort in regard to the functional risks of
      homonymous hemianopia.

PMID- 29600912
TI  - Reduced risk of venous thromboembolism with the use of intermittent pneumatic
      compression after craniotomy: a randomized controlled prospective study.
AB  - OBJECTIVE The term "venous thromboembolism" (VTE) subsumes deep venous thrombosis
      (DVT) and pulmonary embolism. The incidence of DVT after craniotomy was reported
      to be as high as 50%. Even clinically silent DVT may lead to potentially fatal
      pulmonary embolism. The risk of VTE is correlated with duration of surgery, and
      it appears likely that it develops during surgery. The present study aimed to
      evaluate intraoperative use of intermittent pneumatic compression (IPC) of the
      lower extremity for prevention of VTE in patients undergoing craniotomy. METHODS
      A total of 108 patients undergoing elective craniotomy for intracranial pathology
      were included in a single-center controlled randomized prospective study. In the
      control group, conventional compression stockings were worn during surgery. In
      the treatment group, IPC of the calves was used in addition. The presence of DVT
      was evaluated by Doppler sonography pre- and postoperatively. RESULTS
      Intraoperative use of IPC led to a significant reduction of VTE (p = 0.029). In
      logistic regression analysis, the risk of VTE was approximately quartered by the
      use of IPC. Duration of surgery was confirmed to be correlated with VTE incidence
      (p < 0.01); every hour of surgery increased the risk by a factor of 1.56.
      CONCLUSIONS Intraoperative use of IPC significantly lowers the incidence of
      potentially fatal VTE in patients undergoing craniotomy. The method is easy to
      use and carries no additional risks. ? CLASSIFICATION OF EVIDENCE Type of
      question: therapeutic; study design: randomized controlled trial; evidence: class
      I. Clinical trial registration no.: DRKS00011783 ( https://www.drks.de ).

PMID- 29600913
TI  - Natural history of cavernous sinus meningiomas.
AB  - OBJECTIVE Meningiomas confined to the cavernous sinus (MCSs) are benign tumors.
      Due to the high risk of severe complications, the intracavernous surgical
      procedure was abandoned in favor of radiotherapy. However, the choice of
      treatment remains complicated due to the fact that the natural history of this
      lesion has not yet been described. METHODS The authors studied the natural
      history of this lesion using a prospective series of 53 consecutive patients
      suffering from MCSs. The median follow-up duration was 10.2 years (range 2-25
      years), from 1990 to 2016. RESULTS Patients ranged in age from 30 to 72 years
      (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly
      oculomotor palsy and neuralgia experienced in 28 patients), minor symptoms
      (headache, intermittent diplopia in 15 patients), or incidental findings (10
      patients). Simple symptomatic treatment (short courses of corticosteroids and
      carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases
      experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor
      symptoms (p < 0.0001). All patients with incidental findings remained
      asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and
      42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001).
      The radiographic progression-free survival rates (+/- SD) at 5, 10, and 20 years
      were 90% +/- 4.2%, 82% +/- 5.7%, and 70% +/- 10.2%, respectively. Five patients
      (9.4%) with no evidence of any effect of the initial medical treatment desired
      additional conventional radiation therapy. CONCLUSIONS Because of the capricious,
      unpredictable, and slow growth of MCSs, together with high growth variability
      from one patient to the next, the symptomatic medical treatment of these tumors
      is a highly effective method. This series shows that these lesions are naturally,
      clinically, and radiologically indolent.

PMID- 29600914
TI  - Editorial. Indication and technique for using the Pipeline embolization device to
      treat intracranial aneurysms.

PMID- 29600915
TI  - Predictors of cerebral aneurysm persistence and occlusion after flow diversion: a
      single-institution series of 445 cases with angiographic follow-up.
AB  - OBJECTIVE Flow diversion requires neointimal stent overgrowth to deliver aneurysm
      occlusion. The existing literature on aneurysm occlusion is limited by
      heterogeneous follow-up, variable antiplatelet regimens, noninvasive imaging
      modalities, and nonstandard occlusion assessment. Using a large, single-center
      cohort with low attrition and standardized antiplatelet tapering, the authors
      evaluated outcomes after flow diversion of anterior circulation aneurysms to
      identify predictors of occlusion and aneurysm persistence. METHODS Data from a
      prospective, IRB-approved database was analyzed for all patients with anterior
      circulation aneurysms treated by flow diversion with the Pipeline embolization
      device (PED) at the authors' institution. Follow-up consisted of catheter
      cerebral angiography at 6 and 12 months postembolization. Clopidogrel was
      discontinued at 6 months and aspirin was reduced to 81 mg daily at 12 months.
      Occlusion was graded as complete, trace filling, entry remnant, or aneurysm
      filling. Multivariate logistic regression was performed to identify predictors of
      aneurysm persistence. RESULTS Follow-up catheter angiography studies were
      available for 445 (91%) of 491 PED procedures performed for anterior circulation
      aneurysms between August 2011 and August 2016. Three hundred eighty-seven
      patients accounted for these 445 lesions with follow-up angiography. The
      population was 84% female; mean age was 56 years and mean aneurysm size was 6.6
      mm. Aneurysms arose from the internal carotid artery (83%), anterior cerebral
      artery (13%), and middle cerebral artery (4%). Morphology was saccular in 90% of
      the lesions, and 18% of the aneurysms has been previously treated. Overall,
      complete occlusion was achieved in 82% of cases at a mean follow-up of 14 months.
      Complete occlusion was achieved in 72%, 78%, and 87% at 6, 12, and 24 months,
      respectively. At 12 months, adjunctive coiling predicted occlusion (OR 0.260, p =
      0.036), while male sex (OR 2.923, p = 0.032), aneurysm size (OR 3.584, p =
      0.011), and incorporation of a branch vessel (OR 2.206, p = 0.035) predicted
      persistence. Notable variables that did not predict aneurysm occlusion were prior
      treatments, vessel of origin, fusiform morphology, and number of devices used.
      CONCLUSIONS This is the largest single-institution study showing high rates of
      anterior circulation aneurysm occlusion after Pipeline embolization. Predictors
      of persistence after flow diversion included increasing aneurysm size and
      incorporated branch vessel, whereas adjunctive coiling predicted occlusion.

PMID- 29600916
TI  - Risk factors for and outcomes of postoperative complications in adult patients
      with moyamoya disease.
AB  - OBJECTIVE The risk factors and clinical significance of postoperative
      complications in moyamoya disease are still unclear. The aim of this study was to
      investigate the predictors of postoperative complications in moyamoya disease and
      examine the impact of complications on outcomes. METHODS The authors reviewed
      consecutive cases involving adult moyamoya disease patients who underwent
      indirect, direct, or combined bypass surgery in their hospital between 2009 and
      2015. Preoperative clinical characteristics and radiographic features were
      recorded. Postoperative complications within 14 days after surgery were examined.
      Multivariate logistic regression analyses were performed to identify the risk
      factors for either postoperative ischemia or postoperative cerebral
      hyperperfusion. Outcome data, including recurrent strokes and neurological status
      (modified Rankin Scale [mRS]) during follow-up, were collected. Outcomes were
      compared between patients who had complications with those without complications,
      using propensity-score analysis to account for between-group differences in
      baseline characteristics. RESULTS A total of 500 patients (610 hemispheres) were
      included in this study. Postoperative complications were observed in 74
      operations (12.1%), including new postoperative ischemia in 30 cases (4.9%),
      hyperperfusion in 27 (4.4%), impaired wound healing in 12 (2.0%), and subdural
      effusion in 6 (1.0%). The complication rates for different surgery types were as
      follows: 12.6% (n = 25) for indirect bypass, 12.7% (n = 37) for direct bypass,
      and 10.0% (n = 12) for combined bypass (p = 0.726). Postoperative ischemic
      complications occurred in 30 hemispheres (4.9%) in 30 different patients, and
      postoperative symptomatic hyperperfusion occurred after 27 procedures (4.4%).
      Advanced Suzuki stage (OR 1.669, 95% CI 1.059-2.632, p = 0.027) and preoperative
      ischemic presentation (OR 5.845, 95% CI 1.654-20.653, p = 0.006) were
      significantly associated with postoperative ischemia. Preoperative ischemic
      presentation (OR 5.73, 95% CI 1.27-25.88, p = 0.023) and admission modified
      Rankin Scale (mRS) score (OR 1.81, 95% CI 1.06-3.10, p = 0.031) were
      significantly associated with symptomatic postoperative cerebral hyperperfusion
      syndrome (CHS). Compared with patients without postoperative complications,
      patients who experienced any postoperative complications had longer hospital
      stays and worse mRS scores at discharge (both p < 0.0001). At the final follow
      up, no significant differences in functional disability (mRS score 3-6, 11.9% vs
      4.5%, p = 0.116) and future stroke events (p = 0.513) between the 2 groups were
      detected. CONCLUSIONS Advanced Suzuki stage and preoperative ischemic
      presentation were independent risk factors for postoperative ischemia; the mRS
      score on admission and preoperative ischemic presentation were independently
      associated with postoperative CHS. Although patients with postoperative
      complications had worse neurological status at discharge, postoperative
      complications had no associations with future stroke events or functional
      disability during follow-up.

PMID- 29600917
TI  - Letter to the Editor. Prior ablative procedure: a prognostic factor for poor
      outcome of microvascular decompression?

PMID- 29600918
TI  - Preface.

PMID- 29600919
TI  - [Motion sickness in motion: from carsickness to cybersickness].
AB  - - Motion sickness is not a disorder, but a normal response to a non-normal
      situation in which movement plays a central role, such as car travel, sailing,
      flying, or virtual reality.- Almost anyone can suffer from motion sickness, as
      long as at least one of the organs of balance functions. If neither of the organs
      of balance functions the individual will not suffer from carsickness,
      seasickness, airsickness, nor from cybersickness. - 'Cybersickness' is a form of
      motion sickness that is stimulated by artificial moving images such as in
      videogames. Because we are now exposed more often and for longer periods of time
      to increasingly realistic artificial images, doctors will also encounter cases of
      motion sickness more often. - The basis for motion sickness is the vestibular
      system, which can be modulated by visual-vestibular conflicts, i.e. when the
      movements seen by the eyes are not the same as those experienced by the organs of
      balance.- Antihistamines can be effective against motion sickness in everyday
      situations such as car travel if taken before departure, but the effectiveness of
      medication for motion sickness is limited.

PMID- 29600920
TI  - [Death after a fall in patients with advanced dementia: cause of death natural or
      unnatural?]
AB  - OBJECTIVE: This article describes and discusses the viewpoints of elderly care
      physicians and municipal coroners regarding the qualification of natural or
      unnatural deaths of nursing home residents with advanced dementia who fall.
      DESIGN: A digital questionnaire was sent to all elderly care physicians-in
      training and their trainers in the Netherlands, and to all 23 municipal coroners
      in the Mid-Holland region. METHOD: As well as questions on knowledge of the Dutch
      law and prognostic figures concerning dementia-related death, the questionnaire
      described two cases with minimal differences. The respondents were asked if they
      would issue a certificate of natural death in each case, and if not, would they
      have preferred to do so. They were also asked to explain their answers. RESULTS:
      Of the 405 elderly care physicians who responded, 68% and 49%, respectively,
      would have issued a certificate stating the cause to be natural death in each
      case, or if they did not they would have preferred to do so. All 15 coroners who
      filled in the questionnaire came to the conclusion of unnatural death.
      CONCLUSION: The majority of the elderly care physicians feel that a certificate
      of natural death can be issued if a fall in a nursing home results in a fracture,
      as this can be considered as part of the disease process of dementia.

PMID- 29600921
TI  - [Hospital of diagnosis influences the probability of receiving curative treatment
      for oesophageal and gastric cancer].
AB  - OBJECTIVE: The aim of these studies was to examine the influence of hospital of
      diagnosis on the probability of receiving curative treatment and its impact on
      survival among oesophageal and gastric cancer. DESIGN: Although oesophageal and
      gastric cancer surgery is centralised in the Netherlands, the disease is often
      diagnosed in hospitals that do not perform this procedure. METHOD: Patients with
      potentially curable oesophageal or gastric cancer tumours diagnosed between 2005
      and 2013 were selected from the Netherlands Cancer Registry. The probability to
      undergo curative treatment was examined for each hospital of diagnosis after
      adjustment for case-mix. Effects of variation in probability of undergoing
      curative treatment among these hospitals on survival were investigated Cox
      regression. RESULTS: All 13,017 patients with potentially curable oesophageal and
      5,620 patients with potentially curable gastric cancer, diagnosed in 91
      hospitals, were included. After adjustment, the proportion of oesophageal cancer
      patients receiving curative treatment ranged from 50% to 82% and from 48% to 78%
      for patients with gastric cancer in 2010-2013, depending on hospital of diagnosis
      (both P < 0.001). Furthermore, patients diagnosed in hospitals with a low
      probability of undergoing curative treatment had a worse overall survival in the
      period 2010-2013 (oesophageal cancer hazard ratio (HR): 1,15; 95%-CI: 1,07-1,24;
      gastric cancer HR: 1,21; 95%-CI: 1,04-1,41). CONCLUSION: The variation in
      probability of undergoing potentially curative treatment for oesophageal and
      gastric cancer between hospitals of diagnosis and its impact on survival
      indicates that treatment decision-making for these patients may be improved.
      Regional expert multidisciplinary team meetings in this field may improve the
      selection of patients for curative treatment.

PMID- 29600922
TI  - [Trimethylaminuria: 'Help, my child smells of fish!']
AB  - BACKGROUND: Trimethylaminuria is caused by a functional enzyme defect and is
      usually congenital. This metabolic disease is characterised by body odour
      resembling fish. CASE DESCRIPTION: A 7-year-old boy was referred with abnormal
      body odour, which his mother described as resembling fish. This odour caused
      mainly social problems. Because of the characteristic odour trimethylaminuria was
      considered. Further metabolic investigations showed a high concentration of
      trimethylamine in the urine, consistent with this diagnosis. CONCLUSION:
      Trimethylaminuria is rare, but due to its psychological and social impact it is
      important that it is recognised. Although bad body odour is seldom a
      manifestation of a metabolic disease, it should always be included in the
      differential diagnosis.

PMID- 29600923
TI  - [Value-based healthcare: opportunities for better healthcare quality at a lower
      cost].
AB  - The introduction of 'value' as a goal in healthcare requires a change of
      thinking. Quality becomes a leading principle. Transparency will lead to better
      care in hospitals that compare their results with each other. Making quality
      visible together creates the group pressure this requires. Professional and
      patient organisations cannot stay behind when reducing costs. Physicians and
      patients should contribute to providing cheaper care. Concentrating care also
      helps to reduce costs. Hospital data will have to be processed to help patients
      select a treatment. This requires substantial investments in ICT. More attention
      should be given to the entire care chain. In science, the focus should shift from
      evidence-based to quality-based medicine. 'Value-based healthcare' turns the
      medical world on its head and requires time, patience and adjustment. This will
      repay itself in better quality, lower costs, higher satisfaction and more control
      for patients when making decisions about their treatment.

PMID- 29600924
TI  - [Power, you can never have enough of it].
AB  - - In randomised trials on the effects of a medical treatment, the power of the
      trial corresponds to the conditional probability that the conclusion of the trial
      will be that the treatment is effective, given a certain treatment effect.- The
      time to consider the power of a trial is before conducting the study, to ensure
      that the design of the trial is such that there is a reasonable chance of
      demonstrating a clinically relevant effect.

PMID- 29600925
TI  - ?
AB  - A 7-year-old boy was referred to the paediatric clinic with a swollen cheek since
      one day. Intraoral examination revealed erythematous and swollen gingivae in the
      right upper quadrant. The consulted maxillofacial surgeon diagnosed him with a
      canine fossa abscess. The patient recovered quickly after incision and drainage,
      followed by antibiotic therapy.

PMID- 29600926
TI  - [Challenges in the diagnostic management of fat embolism syndrome - from
      divergence in clinical presentation to diagnosis].
AB  - This article discusses the diagnosis and management of two patients with cerebral
      fat embolism syndrome after traumatic femoral fractures. Fat embolism syndrome is
      a condition which is caused by fat globules in the systemic circulation; it most
      often occurs in patients with femoral fractures. Patients develop systemic
      dysfunction, particularly a triad of a petechial rash, respiratory and
      neurological dysfunction. The syndrome is characterized by a diverse clinical
      presentation which often necessitates a wide differential diagnosis. The
      pathogenesis of fat embolism syndrome has not yet been fully elucidated. Although
      it has been a formally recognised clinical diagnosis for years, new diagnostic
      imaging capabilities have provided a shift towards a visualisable disorder.
      Presently, there is no clear evidence and indication for dedicated treatment and
      therefore supportive measures remain the only treatment modality.

PMID- 29600927
TI  - [A child with abdominal pain and fever: consider acute lobar nephritis -
      diagnostic considerations when the appendix is invisible on ultrasound].
AB  - Acute lobar nephritis (ALN) is a focal interstitial bacterial infection of the
      renal parenchyma. ALN is described as a midpoint between an acute pyelonephritis
      and renal abscess. ALN is underdiagnosed in children due to both non-specific
      symptoms and negative urinalysis/bacteriuria laboratory findings. The gold
      standard for diagnosis of ALN is CT scanning, however MRI can be considered to
      avoid radiation exposure. Diagnosing ALN is relevant, because it requires
      prolonged antibiotic treatment. Insufficient antibiotic treatment could cause
      renal scarring and subsequent hypertension or renal failure. Outpatient follow-up
      is indicated to exclude congenital urogenital abnormalities. We describe two
      paediatric patients with acute abdominal pain and fever who were suspected to
      have appendicitis (appendix not visualised by ultrasonography), but eventually
      were diagnosed with ALN and a renal abscess (despite absence of pyuria). These
      reports serve to highlight the issues around the recognition and diagnosis of ALN
      in children, and the need for clinicians to be mindful of this condition.

PMID- 29600928
TI  - [Bacteriophages in the battle against multidrug resistant bacteria].
AB  - Bacteriophages are viruses that infect bacteria. They are highly specific for a
      bacterial species. The so-called 'lytic phages' can lyse bacteria when they
      infect them; these phages can be used to treat bacterial infections. Despite a
      century of experience with phage therapy, the evidence for clinical efficacy is
      limited. Side effects are generally considered to be mild. The selection,
      preparation and administration of phages for therapy is laborious, and
      investigations into the clinical benefits are not easy. More research is needed,
      also in the face of the increasing antimicrobial resistance.

PMID- 29600929
TI  - [Paediatric epilepsy surgery; the earlier, the better].
AB  - The first randomised trial of paediatric epilepsy surgery demonstrated what was
      already known for decades among physicians of children with refractory epilepsy:
      surgical treatment is a highly successful treatment option with superior efficacy
      compared to ongoing drug treatment in well-selected surgical candidates. The lack
      of equipoise and the design of the trial - in which half of the children had to
      wait for one year before being offered surgery - raises questions about its
      ethical justification. A shorter duration of epilepsy predicts better cognitive
      and seizure outcomes after surgery. Surgical risks are low, seizure-freedom rates
      are high for specific pathologies, and the chance of spontaneous permanent
      remission is low in children with focal lesional epilepsy. These children should
      be referred for presurgical evaluation early after diagnosis. Benefits of surgery
      may outweigh the limited surgical risks when the lesion is located outside
      eloquent brain areas, even when seizures are well controlled with antiepileptic
      drugs.

PMID- 29600930
TI  - [Report of the Dutch National Health Council on chronic fatigue syndrome].
AB  - In our opinion, the recent report of the Dutch National Health Council on myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS) lacks balance: it is very
      critical on the quality of evidence regarding behavioural interventions, but
      lacks a critical attitude regarding the presumed somatic components of the
      disorder. Without solid evidence, the report coins ME/CFS as a severe multisystem
      disease, and it embraces the diagnostic criteria of the American Institute of
      Medicine. We underscore the remarks in the report that physicians should not be
      reluctant to make diagnosis in patients with the disorder, and that these
      patients should be approached with empathy and respect. Regarding a future
      research programme, there is need for a well-designed research agenda.

PMID- 29600931
TI  - Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic
      progression of rheumatoid arthritis: a systematic literature review.
AB  - OBJECTIVES: To evaluate the effect of biologic disease-modifying anti-rheumatic
      drugs (bDMARDs) on radiographic progression in patients with rheumatoid arthritis
      (RA). METHODS: A systematic review of electronic databases and conference
      proceedings was conducted through January 2015, to identify randomised controlled
      trials (RCTs) and observational studies that assessed the impact of bDMARDs [+/-
      conventional synthetic DMARDs (csDMARDs), mainly methotrexate (MTX)], versus
      csDMARDs alone, on radiographic progression in patients with RA. RESULTS:
      Following screening of >5000 records, 104 publications covering 63 studies were
      included. Of 34 RCTs in patients with early, active (n=13) or established RA
      (n=21) [abatacept (1, 2); adalimumab (4, 2); certolizumab pegol (1, 4);
      etanercept (3, 3); golimumab (1, 4); infliximab (1, 1); rituximab (1, 1);
      tocilizumab (1, 5)], combination therapy with a bDMARD and MTX had a
      significantly greater effect than placebo or MTX alone, in inhibiting
      radiographic progression. This included patients previously unresponsive, or who
      responded incompletely, to MTX treatment alone, and was supported by data from
      observational studies. Findings from a smaller subset of these and other RCTs
      supported superiority of combination therapy over bDMARD monotherapy, and bDMARD
      monotherapy over MTX, in slowing radiographic progression. CONCLUSIONS: There is
      evidence from RCTs with a range of bDMARDs that improvement in radiographic
      outcomes for patients with early or established RA, when used in combination with
      MTX and to a lesser extent as monotherapy, are significantly greater than MTX
      alone. There was no evidence of a difference between bDMARDs on inhibition of
      radiographic progression.

PMID- 29600932
TI  - Dermoscopy as a supportive tool in differential diagnosis of psoriatic arthritis:
      another reason to include such a technique in rheumatology fellow curriculum.

PMID- 29600933
TI  - Retention and clinical response to abatacept in patients with rheumatoid
      arthritis: an Italian perspective.

PMID- 29600934
TI  - Autoimmune or infectious disease? That is the question.

PMID- 29600935
TI  - Rheumatoid arthritis patients achieved better quality of life than systemic lupus
      erythematosus patients at sustained remission.
AB  - OBJECTIVES: In 2004 and 1999, respectively, recent-onset rheumatoid arthritis
      (RA) and systemic lupus erythematous (SLE) cohorts were initiated; the 36 item
      Medical Outcome Study Short-Form survey (SF-36) was applied beginning from
      enrolment. The objectives were to compare the SF-36v2 scores between patients
      from both cohorts who achieved sustained remission and to define the role of
      disease diagnosis as associated to SF-36v2 normative data in remission patients.
      METHODS: Sustained remission was considered when RA and SLE patients achieved at
      least 12 months of continuous follow-up with either SLE disease activity index
      2000 update =0 or Disease Activity Score (28 joints) <=2.4, respectively. Up to
      December 2015, data from 172 RA patients and 211 SLE patients were reviewed. SF
      36v2 scores were available for the totality of remission assessments. Logistic
      regression models were used to investigate factors associated with normative SF
      36v2. Written informed consent was obtained from all patients. RESULTS: A higher
      proportion of patients achieved sustained remission sooner in the RA cohort than
      in the SLE cohort, 58% vs. 30.6% of the patients, after 30.8+/-23.9 vs. 59.4+/
      37.5 months, respectively, p<=0.001. At sustained remission, RA patients scored
      better than SLE patients in 6 out of 8 domains of the SF-36v2 and the physical
      health component summary (PHCS); the opposite figure was true for the mental
      component. Age (beta: 1.06, 95% CI: 1.02-1.1, p=0.03) and SLE diagnosis (beta:
      9.64, 95% CI: 3.61-25.75, p<=0.001) were predictors of not achieving normative
      PHCS. CONCLUSIONS: RA patients in sustained remission achieved better quality of
      life than SLE patients.

PMID- 29600937
TI  - Low dose of simvastatin reduces disease activity and improves endothelial
      function in patients with SLE.

PMID- 29600936
TI  - Association between primary Sjogren's syndrome, cardiovascular and
      cerebrovascular disease: a systematic review and meta-analysis.
AB  - OBJECTIVES: Acute systemic inflammation and chronic systemic vasculitis are
      associated with endothelial dysfunction and atherosclerotic plaque formation.
      Studies on cardiovascular or cerebrovascular events in primary Sjogren's syndrome
      (pSS) are limited, with conflicting results. This meta-analysis aimed to explore
      the risk of cardiovascular and cerebrovascular disease in pSS. METHODS: A
      comprehensive search of the MEDLINE and EMBASE databases was performed from date
      of inception through August 2017. The inclusion criterion was observational
      studies evaluating the association between pSS and cardiovascular disease or
      cerebrovascular event. Outcomes are diagnosis of ischaemic heart disease,
      myocardial infarction, ischaemic stroke or haemorrhagic stroke. The pooled odds
      ratio (OR) of the cerebrovascular event or cardiovascular disease and their 95%
      confidence interval (CI) were calculated using a random-effect meta-analysis to
      compare risk between patients with pSS and controls. The between-study
      heterogeneity of effect-size was quantified using the Q statistic and I2.
      RESULTS: Data were extracted from 10 observational studies involving 165,291
      subjects. Pooled result demonstrated a significant increase in risk of having
      cardiovascular disease or cerebrovascular event in pSS patients compared with
      controls (OR=1.28; 95% CI: 0.11-1.46, p value<0.01, I2=68%). Subgroup analyses
      showed no difference in risk for cerebrovascular event (OR=1.31; 95% CI: 0.96
      1.79, p value=0.09, I2=71%), but an increased risk of cardiovascular disease
      (OR=1.30; 95% CI: 1.09-1.55, p value=0.003, I2=74%). CONCLUSIONS: Our study has
      shown an increased risk of cardiovascular or cerebrovascular disease in patients
      with pSS. These results support multiple studies' finding of increased arterial
      stiffness in patients with pSS.

PMID- 29600938
TI  - Detection of human T lymphotropic virus type-I bZIP factor and tax in the
      salivary glands of Sjogren's syndrome patients.
AB  - OBJECTIVES: To detect HTLV-I bZIP factor (HBZ), tax and relevant molecules in
      labial salivary glands (LSGs) from patients with Sjogren's syndrome (SS).
      METHODS: The expressions of HBZ and tax in T cell lines and LSGs were analysed by
      in situ hybridization (ISH) or real time PCR. The expressions of forkhead box P3
      (Foxp3) and p65 in immunohistochemistry were quantified. RESULTS: After
      specificity of ISH probes was determined in 5 T cell lines, in LSGs from an adult
      T-cell leukemia (ATL) patient and 3 HTLV-I-associated myelopathy (HAM)-SS
      patients, both HBZ and tax signals were detected in infiltrating mononuclear
      cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of ATL
      and HAM-SS, respectively. HBZ was dominantly observed in LSGs from 8 HTLV-I
      asymptomatic carrier (AC)-SS patients; faint expression of HBZ was observed in
      LSGs from 5 HTLV-I-seronegative SS patients. No cell adhesion molecule 1(CADM1)
      expressed in LSGs from the ATL patient. Although Foxp3 expression was observed in
      LSG MNCs of all of the SS patients, the ATL patient's expression was
      significantly greater than that of the AC-SS (p<0.01) and HTLV-I-seronegative SS
      (p<0.01) patients. The Foxp3 expression was similar in ATL and HAMSS, but
      significantly higher in HAM-SS than AC-SS (p<0.05). p65 was expressed in LSG MNC
      nuclei from all SS patients and co-expressed with Foxp3. The expressions of Foxp3
      in ducts differed according to HTLV-I infection. CONCLUSIONS: These results
      suggest that HBZ-mediated Foxp3 expression is partly associated with the
      pathogenesis of HTLV-I-seropositive SS.

PMID- 29600939
TI  - Chinese registry of rheumatoid arthritis (CREDIT): I. Introduction and prevalence
      of remission in Chinese patients with rheumatoid arthritis.
AB  - OBJECTIVES: To introduce the Chinese Registry of rhEumatoiD arthrITis (CREDIT),
      which is the first nationwide, multicentre, online rheumatoid arthritis (RA)
      registry in China, and to depict major cross-sectional data and treatment
      strategies of Chinese RA patients. METHODS: RA patients who fulfilled the 2010
      ACR/EULAR classification criteria for rheumatoid arthritis were recruited into
      the registry by their rheumatologists from 144 clinical centres in China. Data,
      including demographics, disease characteristics, co-morbidities, treatment, and
      adverse reactions, were collected and documented through the predefined protocol.
      RESULTS: 8071 registered patients (F:M = 4.03:1) were registered up to May 2017.
      Mean age at symptom onset and at diagnosis was 46.15+/-14.72y and 48.68+/-14.54y,
      respectively. Point prevalence of remission (95% CIs) was 14.88% (14.10-15.66%),
      4.23% (3.79-4.66%), 4.25% (3.81-4.69%), and 4.27% (3.83-4.72%) according to DAS28
      CRP, CDAI, SDAI, and the 2011 ACR/EULAR remission criteria, respectively. 38.84%
      and 38.11% of treatment-naive patients (n=3262) were in moderate (3.2<DAS28
      CRP<=5.1) and high (DAS28-CRP>5.1) disease activity, respectively. Among
      treatment-naive patients, those who were initiated on treatment with bDMARDs had
      higher disease activity than those who were treated with csDMARDs (p<0.05). Three
      months after initiating bDMARDs, 19.29% (n=38) of patients achieved remission
      (DAS28-CRP<2.6). CONCLUSIONS: The CREDIT registry is an effective tool for real
      world study of RA patients in China. By providing information for diagnosis and
      treatment regimen, the CREDIT registry can enhance the application of treat-to
      target (T2T) strategy and improve patient outcomes in China.

PMID- 29600940
TI  - The burden of systemic juvenile idiopathic arthritis for patients and caregivers:
      an international survey and retrospective chart review.
AB  - OBJECTIVES: To investigate the burden of systemic juvenile idiopathic arthritis
      (SJIA) on health-related quality of life (HRQOL) and resource use of patients and
      caregivers (families) on biologic therapy. METHODS: This international study
      assessed SJIA burden in patients on biologics, using a caregiver questionnaire
      and retrospective chart review. Validated measures included: Child Health
      Questionnaire Parent-Form 50 (CHQ-PF50), 36-Item Short-Form Health Survey (SF
      36v2) and Work Productivity and Activity Impairment questionnaire: Specific
      Health Problem (WPAI:SHP). Caregivers completed function, treatment satisfaction
      and resource utilisation questions. RESULTS: Sixty-one biologic treated patients
      participated (12 anakinra, 25 canakinumab, 24 tocilizumab). Mean age at diagnosis
      and survey completion was 6.4 and 11.3 years, respectively. Mean (+/-SD: standard
      deviation) CHQ-PF50 physical (PhS) and psychosocial (PsS) summary scores were
      significantly lower in SJIA patients than a normative population (PhS: 40.0+/
      18.2 vs. 53.0+/-8.8; PsS: 46.6+/-11.3 vs. 51.2+/-9.1) as was caregivers' mean SF
      36v2 mental component score (MCS; 46.2+/-10.7 vs. 50.0+/-10). Assistive devices
      were required by 54%; 20% required home/car alterations. According to caregivers,
      biologic treatment completely improved SJIA symptoms in 48% on canakinumab or
      tocilizumab and 32% on anakinra. Over 2 months, patients missed 2.9 school days
      due to SJIA (10% yearly loss). Caregivers lost 25 work days annually and 27.5
      days of productivity (WPAI-SHP: mean absenteeism 10%; presenteeism 11%). Yearly
      SJIA travel/treatment costs averaged $1,130. CONCLUSIONS: SJIA patients on
      biologic therapy experience HRQOL impairment, caregivers' mental well-being
      suffers and productivity losses and expenses are incurred. Therapeutic
      interventions that reduce the burden of SJIA are required.

PMID- 29600941
TI  - Adalimumab biosimilar in rheumatoid arthritis: a total-evidence assessment to
      evaluate equivalence with the originator based on network meta-analysis.

PMID- 29600942
TI  - Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with
      disease activity in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To study the prevalence of asymptomatic activation of Epstein-Barr
      virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the
      correlation of serum EBV DNA with the disease activity. METHODS: The level of EBV
      DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive
      early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples
      from 31 ERA and 16 CRA patients were obtained after starting or modifying the
      anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and
      9 patients with adult onset Still's disease (AOSD). Disease activity was assessed
      by the disease activity score (DAS28). RESULTS: At baseline, EBV DNA was detected
      in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease
      activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At
      baseline EBV positive patients had significantly higher disease activity
      (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28
      (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset
      and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had
      significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated
      significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls
      and none of the AOSD patients were positive for EBV DNA. CONCLUSIONS: Active RA
      is associated with a lytic EBV infection which may have a role in the
      pathogenesis of RA.

PMID- 29600943
TI  - Silent arterial inflammation during the apparent remission state of Takayasu's
      arteritis. What do cytokines tell us?
AB  - OBJECTIVES: To evaluate serum cytokines as biomarkers of smoldering disease
      activity in patients with Takayasu's arteritis (TAK) in remission. METHODS:
      Thirty-four TAK patients with stable disease during the last 6 months and 22
      healthy controls (HC) were included in a cross-sectional study. Serum levels of
      pro-inflammatory, anti-inflammatory, Th1, Th2, Th9, Th17 and Th22 cytokines were
      measured by the multiplex technique. RESULTS: No significant differences
      regarding serum cytokine levels were found between TAK patients and HC. Serum TNF
      alpha, IL-17F, IL-21 and IL-23 were higher in patients presenting angiographic
      type V than in those presenting other angiographic types. Serum IL-17E, IL-17F,
      IL-22 and IL-23 were higher in TAK patients with previous ischaemic events
      compared with those without previous ischaemia. No differences in serum cytokines
      were observed between TAK patients with and without aneurysmal disease in the
      aorta or among TAK patients without therapy, those under immunosuppressive agents
      and patients on biological therapy. Independent associations were found regarding
      angiographic type V and higher serum levels of IL-4, IL-6, IL17A, IL-17E, IL-17F,
      IL-21, IL-22 and IL-23. Previous ischaemic events were independently associated
      with higher serum IL-4, IL-17E, IL-22 and IL-23. Daily prednisone dose had an
      inverse association with lower serum IL-4, IL6, IL-17A, IL-17E, IL-22 and IL-23.
      The simultaneous use of immunosuppressive and biological agents led to lower
      serum IL-4, IL-17E and IL-23 levels. CONCLUSIONS: A smoldering inflammatory
      response with predominantly cytokines involved in Th17 response seems to be
      ongoing in TAK patients in remission with extensive disease or with previous
      ischaemic events.

PMID- 29600944
TI  - Investigation of serum biomarkers in primary gout patients using iTRAQ-based
      screening.
AB  - OBJECTIVES: Primary gout is a major disease that affects human health; however,
      its pathogenesis is not well known. The purpose of this study was to identify
      biomarkers to explore the underlying mechanisms of primary gout. METHODS: We used
      the isobaric tags for relative and absolute quantitation (iTRAQ) technique
      combined with liquid chromatography-tandem mass spectrometry to screen
      differentially expressed proteins between gout patients and controls. We also
      identified proteins potentially involved in gout pathogenesis by analysing
      biological processes, cellular components, molecular functions, Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein
      interactions. We further verified some samples using enzyme-linked immunosorbent
      assay (ELISA). Statistical analyses were carried out using SPSS v. 20.0 and ROC
      (receiver operating characterstic) curve analyses were carried out using Medcalc
      software. Two-sided p-values <0.05 were deemed to be statistically significant
      for all analyses. RESULTS: We identified 95 differentially expressed proteins (50
      up-regulated and 45 down-regulated), and selected nine proteins (alpha-enolase
      (ENOA), glyceraldehyde-3-phosphate dehydrogenase (G3P), complement component C9
      (CO9), profilin-1 (PROF1), lipopolysaccharide-binding protein (LBP), tubulin beta
      4A chain (TBB4A), phosphoglycerate kinase (PGK1), glucose-6-phosphate isomerase
      (G6PI), and transketolase (TKT)) for verification. This showed that the level of
      TBB4A was significantly higher in primary gout than in controls (p=0.023).
      CONCLUSIONS: iTRAQ technology was useful in the selection of differentially
      expressed proteins from proteomes, and provides a strong theoretical basis for
      the study of biomarkers and mechanisms in primary gout. In addition, TBB4A
      protein may be associated with primary gout.

PMID- 29600945
TI  - Lofgren syndrome as secondary autoimmune disease in a patient with B-cell
      depletion following rituximab treatment.

PMID- 29600946
TI  - Diagnosis of deficiency of adenosine deaminase 2 with early onset polyarteritis
      nodosa in an adult patient with a novel compound heterozygous CECR1 mutation.

PMID- 29600947
TI  - Disease activity, overweight, physical activity and screen time in a cohort of
      patients with juvenile idiopathic arthritis.
AB  - OBJECTIVES: Physical activity is an important part of children's health and
      social development. Juvenile idiopathic arthritis (JIA) can lead to decreased
      physical activity and quality of life. This study characterised clinical aspects,
      physical activity rates, obesity, and screen time in a group of JIA patients.
      METHODS: Ninety-seven JIA patients in the Paediatric Rheumatology Clinic at Meir
      Medical Center were evaluated over a 6-month period and compared by statistical
      methods to 98 age-matched healthy controls. Information on disease activity, type
      and amount of physical activity (using the Modified Godin Leisure-Time Exercise
      Questionnaire), and daily screen time hours were collected. RESULTS: Among the
      JIA patients, 56% had oligoarthritis, 22% polyarthritis and 17% systemic disease.
      Disease activity among all JIA sub-groups was low (average of 1.7/10), two-thirds
      of patients had disease activity lower than 3, only 4% over 5, and 56% were in
      clinical remission. Obesity rates in the patient and control groups were 21.5%
      and 19.4%, respectively. Physical activity levels were similar in both groups.
      Age at onset of disease and physical activity rate were negatively correlated (r=
      0.288, p=0.004). Total weekly leisure activity of the control group was higher
      (46.9 vs. 38.4 hours, respectively), while daily screen time was similar (3.2 vs.
      2.9 hours, respectively). CONCLUSIONS: Physical activity, obesity rates and
      screen time hours were similar between JIA patients and controls. This lack of
      difference could be attributed to clinical remission following early, aggressive,
      treat-to-target therapy.

PMID- 29600948
TI  - Intraarticular infliximab therapy in patients with juvenile idiopathic arthritis:
      the role of musculoskeletal ultrasound and disease activity scores in monitoring
      therapy response.
AB  - OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common chronic
      rheumatic disease in children, with heterogeneous clinical features. Although
      therapeutic options are wide and in the majority of children symptoms improve
      with the combination of non-steroidal anti-inflammatory and disease-modifying
      drugs, there are a number of patients who do not respond to conventional therapy
      and who do not meet the criteria for systemic biologics, namely anti TNF-alpha.
      Those patients are potential candidates for intraarticular therapy with biologics
      and in this report we present the results of intra-articular infliximab treatment
      in a series of patients diagnosed with oligoarticular subtype of JIA. METHODS:
      Twenty patients (30 joints) were treated with intraarticular infliximab and
      monitored by power Doppler musculoskeletal ultrasound according to the OMERACT
      and Juvenile Arthritis Disease Activity Score (JADAS 10) before intraarticular
      application and during the follow-up period of 18 months (0, 1, 12, 18 months).
      RESULTS: The results showed statistically significant improvement in PD-MSUS
      measures and JADAS in both B mode and power Doppler mode scores (p<0.001,
      p<0.001, respectively) in patients treated with i.a. infliximab with persistent
      response in fifteen patients. The JADAS score, as well as the ultrasound scores,
      were significantly reduced during the follow-up period. CONCLUSIONS: This study
      showed promising results, good safety and potential for the clinical benefit of
      intraarticular infliximab treatment in a selected group of patients with
      oligoarticular subtype of JIA.

PMID- 29600949
TI  - Clinical remission in rheumatoid arthritis and psoriatic arthritis.
AB  - It is currently recognised that remission can be an achievable target for several
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients by a treat-to
      target approach. For RA different remission criteria have been proposed,
      depending on the disease activity scores used, on the importance given to the
      inclusion of patients' perspective into the definition of remission, and on their
      applicability in clinical practice, that generate highly different remission
      rates. Conversely, for PsA, remission is still insufficiently defined and
      represents a partially unmet need. For both conditions, several first- and second
      line treatment strategies are now available - disease-modifying anti-rheumatic
      drugs (DMARDs) of synthetic and biologic origin - that make the achievement of
      remission or at least low/minimal disease activity a realistic goal. This paper
      is a narrative review of the different criteria of remission, in the light of the
      available treatment strategies for RA and PsA, and in the attempt to provide
      rheumatologists an opportunity to improve the outcome to the greatest extent
      possible in their clinical practice.

PMID- 29600950
TI  - Diagnostic and predictive evaluation using salivary gland ultrasonography in
      primary Sjogren's syndrome.
AB  - OBJECTIVES: We aimed to assess the diagnostic accuracy of salivary gland
      ultrasonography (SGUS) as a single test for the detection of primary Sjogren's
      syndrome (pSS) and examine the prognostic factors for severe structural damage of
      the salivary glands based on SGUS score. METHODS: Patients with pSS (n=94) and
      idiopathic sicca syndrome (n=44) were evaluated using the SGUS 0-48 scoring
      system, which comprises five parameters: parenchymal echogenicity, homogeneity,
      hypoechoic areas, hyperechogenic reflections, and clearness of posterior borders.
      The salivary gland volume and intraglandular power Doppler signal (PDS) were also
      assessed. A multivariate linear regression analysis was performed to determine
      the factors associated with SGUS score. RESULTS: Patients with pSS showed a
      significantly higher SGUS score than controls [median (IQR): 24.5 (13.0) vs 6
      (3.75), p<0.001]. An SGUS cut-off of >=14 had a sensitivity of 80.9% and a
      specificity of 95.5% for the diagnosis of pSS. There were no significant
      differences in the measured volumes and PDS between pSS patients and controls.
      The SGUS score correlated with unstimulated salivary flow rate (USFR), serum
      rheumatoid factor and IgG. Double seropositivity with anti-Ro/SS-A and anti-La/SS
      B (beta=6.060, p=0.001) and USFR (beta=-1.913, p<0.001) were independently
      associated with the SGUS score. CONCLUSIONS: The SGUS scoring system is a
      valuable diagnostic method for pSS. Double seropositivity of anti-Ro/SS-A and
      La/SS-B along with USFR were independent predictive factors for structural damage
      of the salivary glands.

PMID- 29600951
TI  - Linear and Nonlinear Dynamics of Heart Rate Variability are Correlated with
      Purpose in Life and Degree of Optimism in Anxiety Disorder Patients.
AB  - Although heart rate variability (HRV) may be a crucial marker of mental health,
      how it is related to positive psychological factors (i.e. attitude to life and
      positive thinking) is largely unknown. Here we investigated the correlation of
      HRV linear and nonlinear dynamics with psychological scales that measured degree
      of optimism and happiness in patients with anxiety disorders. Results showed that
      low- to high-frequency HRV ratio (LF/HF) was increased and the HRV HF parameter
      was decreased in subjects who were more optimistic and who felt happier in daily
      living. Nonlinear analysis also showed that HRV dispersion and regulation were
      significantly correlated with the subjects' optimism and purpose in life. Our
      findings showed that HRV properties might be related to degree of optimistic
      perspectives on life and suggests that HRV markers of autonomic nervous system
      function could reflect positive human mind states.

PMID- 29600952
TI  - Generalized Multiplicative Model for Assessing Outcome in Psychotherapy:
      Subjective Well-Being.
AB  - The study presents the performance of generalized multiplicative model (GMultM)
      for assessing outcome in psychotherapy. GMultM is a flexible nonlinear regression
      method which is able to predict the impact of subjects' psychological variables
      (common factors such as inner directedness, time competence, sociotropy, and
      perfectionism, locus of control, body dissatisfaction, neuroticism, and
      alexithymia) as well as their changes on the outcome of psychotherapy. This
      nonlinear regression model including interaction effects among predictors has a
      higher explanatory power to predict treatment outcome, compared to any linear
      model. Also, GMultMs are accurate and easily interpretable models, compared to
      complex models such as, for example, based on nonlinear dynamics, complexity,
      stochastic optimization control theories, etc. A case study of rhythmic movement
      therapy (RMT) for increasing the level of subjective well-being (SWB) is
      presented. Results revealed that: (a) the GMultM not only predicts the current
      levels of SWB satisfactorily but also allows obtaining the partial response
      functions of psychological predictors of SWB directly as a result of estimation
      of model's parameters; (b) GMultM predicts the changes in SWB after RMT
      intervention in each participant satisfactorily and thus can be applied as the
      individualized assessment tool for psychotherapy's outcome.

PMID- 29600953
TI  - Multi-day Patterns around Taking Action in Intimate Partner Violence.
AB  - This study was to determine the multi-day relationships among stressors, need and
      taking action (seeking counseling, taking legal action, leaving) by women in
      violent relationships. Women with recent husband-to-wife abuse but not at high
      risk for life-threatening violence were recruited from six primary care clinics
      and asked to complete a daily description of the previous day's violence, need
      for-action, and stressors using Interactive Voice Response via telephone for 8
      weeks. Taking action (seeking counseling, taking legal action, leaving) was
      determined via weekly telephone contacts. To identify day-to-day recurrent
      strings, we used orbital decomposition, limiting time series to 29 women who took
      action during the study. Multi-day patterns were not common in taking action and
      are unrelated to violence. Only one 5-day string involving seeking counseling was
      identified in which women felt a lack of control. While taking legal action was
      part of five 5-days strings, each string consisted of one day of taking legal
      action within four days of no need-for-action, violence or stalking. Finally, one
      4-day string that began with leaving coupled with spouse's excessive alcohol
      intake but no violence was noted. Hence, decisions to take action in violent
      relationships are not typically multi-day decisions linked to violence, but
      rather sudden events triggered by loss of control, his alcohol intake or unique
      situational factors.

PMID- 29600954
TI  - On the Pervasiveness of Long Range Memory Processes in Daily High School
      Attendance Rates.
AB  - Few educational researchers or practitioners would question that high school
      attendance is an important mediator in the causal network that is used to explain
      academic achievement, yet attendance remains under-researched. The New York City
      Department of Education (NYCDOE) has created an opportunity to examine the
      longitudinal trends and dependencies in daily attendance rates as it created a
      repository of daily attendance rates for all its schools, starting in 2004. The
      present analysis examines the dynamical patterns in daily attendance rates over a
      ten-year period (Sept. 2004 - June 2014) in six small high schools and ten large
      ones. As was done in previous work, this analysis systematically distinguishes
      short range, seasonal and long range dependencies in the data using time series
      analysis. Seasonal cycles are predictable (here, fluctuation by days of the
      week), the long range dependencies indicate cycles that are unpredictable,
      suggestive of more complex dynamical processes, such as self-similarity, self
      organized criticality and scale invariance, features that are difficult to detect
      by school building personnel, but are important aspects of the systems' behavior.
      Seasonal cycles were found in three of the nine large schools and in all six
      small ones. Significant long range dependencies (Hurst exponent) were found in
      all large schools and all but one of the small ones. The pervasiveness of the
      long range processes over and above the seasonal cycles is striking, and may
      suggest an adaptability of these systems to fluctuations in the exogenous
      processes that find their expression in daily attendance behavior (e.g., parental
      involvement). However, this latter interpretation is in need of further empirical
      support.

PMID- 29600955
TI  - Finding Fractal Networks in Literature.
AB  - This paper is about how fractal connections between words can be identified and
      hidden fractal word-networks uncovered in corpus texts. The basis for this
      'search-and-find' procedure is the hypothesis Complexity Connections in Corpuses
      (CCIC) consisting of four separate sub-hypotheses, each the basis of a procedure
      for uncovering a special part of such networks. The validity and applicability of
      CCIC are demonstrated by showing that each sub-hypothesis holds good for twenty
      four masterpieces, selected from the world's great library of novels and
      treatises. And the hidden structure is 'developed' by means of our computer
      program ZIPPF. It turns out that this hidden structure is similar for all
      investigated corpus texts, a fact which, in our thinking, supports the idea that
      the hidden word-network renders us a glimpse of working processes used by the
      brain machinery to produce text. The conclusion is that CCIC provides tools for
      linguistic research, is a supplement to linguistic networks theory, and opens up
      for, inter alia fractal-mathematical, studies of high-level brain/mind activity
      because it follows from CCIC that human verbal thinking is fractal.

PMID- 29600956
TI  - An Eye for Nature.
AB  - Artists have a long tradition of capturing the essence of Nature in their
      creative works. This year's cover artist, Tallmadge Doyle, uses copper plates to
      create prints of the complex visual textures found in Nature's scenery.
      Originating from careful observation, her images then undergo a stylistic
      evolution toward a personalized artistic vision of Nature's textures.

PMID- 29600957
TI  - [Letter to the Editor: Still About Delirium].

PMID- 29600958
TI  - Letter to the Editor re: "Medicine and its Preventive Excesses".

PMID- 29600959
TI  - Letter to the Editor re: "The Role of Medical Students in Short-Term Experiences
      In Global Health: A Perspective From Sao Tome Island".

PMID- 29600960
TI  - Erratum to "Factors Influencing the Implementation of Screening and Brief
      Interventions for Alcohol Use in Primary Care Practices: A Systematic Review
      Protocol".

PMID- 29600962
TI  - Targeting the accomplice to thwart the culprit: a new target for the prevention
      of amyloid deposition.
AB  - Inheritance of the E4 allele of the apolipoprotein E gene (APOE4) substantially
      increases the risk of developing late-onset Alzheimer disease (AD). A large body
      of evidence has firmly established a role for apoE in modulating the risk of
      developing the amyloid plaque pathology that is pathognomonic for AD. In this
      issue of the JCI, Liao and colleagues discovered that antibodies against a
      nonlipidated form of apoE4 are highly effective in delaying the deposition of
      amyloid beta (Abeta) peptides in mouse models of AD pathology. Using a
      combination of passive immunization and viral-mediated expression of recombinant
      antibodies, the authors show that Fc receptor-mediated clearance of the
      nonlipidated apoE4 was critical in delaying Abeta deposition. Collectively, this
      study identifies a new therapeutic target that could be exploited to prevent, or
      possibly reverse, the Abeta pathology of AD.

PMID- 29600961
TI  - Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid
      accumulation.
AB  - The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor
      for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE
      influences Alzheimer disease (AD) in large part by affecting amyloid beta (Abeta)
      aggregation and clearance; however, the molecular mechanism underlying these
      findings remains largely unknown. Herein, we tested whether anti-human apoE
      antibodies can decrease Abeta pathology in mice producing both human Abeta and
      apoE4, and investigated the mechanism underlying these effects. We utilized
      APPPS1-21 mice crossed to apoE4-knockin mice expressing human apoE4 (APPPS1
      21/APOE4). We discovered an anti-human apoE antibody, anti-human apoE 4 (HAE-4),
      that specifically recognizes human apoE4 and apoE3 and preferentially binds
      nonlipidated, aggregated apoE over the lipidated apoE found in circulation. HAE-4
      also binds to apoE in amyloid plaques in unfixed brain sections and in living
      APPPS1-21/APOE4 mice. When delivered centrally or by peripheral injection, HAE-4
      reduced Abeta deposition in APPPS1-21/APOE4 mice. Using adeno-associated virus to
      express 2 different full-length anti-apoE antibodies in the brain, we found that
      HAE antibodies decreased amyloid accumulation, which was dependent on Fcgamma
      receptor function. These data support the hypothesis that a primary mechanism for
      apoE-mediated plaque formation may be a result of apoE aggregation, as
      preferentially targeting apoE aggregates with therapeutic antibodies reduces
      Abeta pathology and may represent a selective approach to treat AD.

PMID- 29600963
TI  - Potential role of hematological parameters in patients with chronic obstructive
      pulmonary disease: current point of view.

PMID- 29600964
TI  - Endothelium, asymmetric dimethylarginine, and atherosclerosis in chronic kidney
      disease.

PMID- 29600965
TI  - Considerations in designing and interpreting prevalence studies for Behcet
      syndrome.

PMID- 29600966
TI  - Asymmetric dimethylarginine as a useful risk marker of radial artery
      calcification in patients with advanced kidney disease.
AB  - INTRODUCTION    Medial arterial calcification is common in patients with chronic
      kidney disease (CKD) and is considered a risk factor for morbidity and mortality.
      OBJECTIVES    We aimed to evaluate the correlation between asymmetric
      dimethylarginine (ADMA) levels, radial artery calcification, and common carotid
      artery intima-media thickness (CCA-IMT). PATIENTS AND METHODS    The study
      included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis
      access was created to collect radial artery samples for a histological
      examination, and 33 healthy volunteers, in whom the reference concentrations of
      ADMA were assessed. The concentrations of creatinine, albumin, calcium,
      phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN),
      osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6,
      interleukin 18, pentraxin 3, stromal cell-derived factor 1alpha (SDF1alpha),
      thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix
      metalloproteinase 2 (MMP-2) were determined. Radial artery fragments were stained
      for calcifications using alizarin red. The CCA-IMT was assessed by
      ultrasonography. RESULTS    Patients with CKD had higher ADMA levels than
      controls. Patients with ADMA levels above the median were older, had higher
      levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP-2,
      thrombomodulin, and they had more atherosclerotic plaques in the carotid artery.
      In multiple regression, log-transformed (log)sTNFRII, MMP-2, and SDF1alpha levels
      were independent predictors of log(ADMA). Patients with calcifications had higher
      ADMA levels. A similar correlation was observed between SDF1alpha and alizarin
      red staining grades 1 to 3. In logistic regression, ADMA levels positively
      predicted the presence of calcifications independently of age, hemodialysis
      status, Framingham risk score, and PTX3. CONCLUSIONS    Circulating ADMA levels
      indicate medial arterial calcification in patients with CKD.

PMID- 29600967
TI  - Ventricular fibrillation induced by radiofrequency energy delivery for premature
      ventricular contractions arising from the right ventricular outflow tract: is
      implantablecardioverterdefibrillator indicated?
AB  - INTRODUCTION    Inadvertently induced ventricular fibrillation (VF) by
      radiofrequency (RF) energy delivery for premature ventricular complexes (PVCs) is
      a rare phenomenon; nevertheless, it is crucial to assess long-term risk of sudden
      cardiac death in these patients. OBJECTIVES    The aim of our study was to define
      the long-term prognosis in patients with normal ejection fraction (EF), in whom
      VF was inadvertently induced by RF energy application during ablation of
      symptomatic idiopathic PVCs originating from the right ventricular outflow tract
      (RVOT). PATIENTS AND METHODS    Among over 20 000 RF catheter ablations performed
      at 5 tertiary centers (2008-2016), 6 patients (5 men) had VF induced by RF
      application to the RVOT. The mean (SD) age of patients was 35.2 (16.8) years. All
      patients had normal EF (>=60%). We analyzed the risk of malignant ventricular
      arrhythmias and assessed heart function during follow-up. RESULTS    After
      ablation, baseline contrast-enhanced magnetic resonance imaging was performed in
      4 of the 6 patients; no area of late gadolinium enhancement was observed. One
      patient received an implantable cardioverter-defibrillator (ICD). Exercise tests
      revealed only rare PVCs. All patients completedthe follow-up (mean [SD] duration
      of follow-up, 64.0 [34.9] months). All patients were alive, with no cases of
      syncope, documented ventricular tachycardia, or VF. The patient with an ICD
      received 2 inappropriate high-voltage therapies. CONCLUSIONS    Patients with
      inadvertently induced VF via RF energy application during ablation of PVCs from
      the RVOT, who have normal left ventricular function and no electrocardiography
      abnormalities have good prognosis and low VF risk during long-term follow-up.
      Therefore, ICD placement seems to be not indicated for these patients.

PMID- 29600968
TI  - Tumor-induced hypophosphatemic osteomalacia as a rare cause of bone pain.

PMID- 29600969
TI  - Undercarboxylated osteocalcin in patients with newly diagnosed type 2 diabetes
      after blood glucose regulation.

PMID- 29600970
TI  - Chronic obstructive pulmonary disease affects angiographic presentation and
      outcomes. Authors' reply.

PMID- 29600971
TI  - Chronic obstructive pulmonary disease affects angiographic presentation and
      outcomes.

PMID- 29600972
TI  - Notes from the Field: Nontuberculous Mycobacteria Infections in U.S. Medical
      Tourists Associated with Plastic Surgery - Dominican Republic, 2017.

PMID- 29600973
TI  - Signatures of anti-Thomsen - Friedenreich antigen antibody diversity in colon
      cancer patients.
AB  - AIM: To determine whether the structural and functional diversities of naturally
      occurring antibodies to the Thomsen - Friedenreich (TF) antigen may be of
      diagnostic and prognostic value in colon cancer. MATERIALS AND METHODS: Serum
      samples were taken from patients with colon cancer (n = 94) and healthy controls
      (n = 64). The level of TF-specific antibody isotypes and their sialylation were
      determined using ELISA and lectin-ELISA with synthetic TF-polyacrylamide
      conjugate as an antigen and a sialic acid-specific Sambucus nigra agglutinin
      (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. The
      accuracy of diagnostics was evaluated using the receiver operator characteristic
      curve analysis and the survival analysis employing the Kaplan - Meier method.
      RESULTS: Compared to healthy controls, patients with colon cancer exhibited a
      lower level of anti-TF IgG antibodies, significantly lower ratios of TF-specific
      IgG/IgM and IgG/IgA, an increased SNA reactivity of anti-TF antibodies, mostly on
      account of IgG, and a lower avidity of TF-specific antibodies, especially their
      SNA-reactive subset. An increased SNA reactivity of anti-TF IgG was observed
      already at the early stages of cancer (p = 0.0004). The decrease of the ratio of
      IgG/IgM and IgG/IgA showed a good accuracy of diagnostics with about 60%
      sensitivity at 90% specificity. A similar potential was found for the SNA
      binding/IgG level index. The high level of TF-specific IgA antibodies was
      associated with a lower survival rate (hazard ratio = 0.34). CONCLUSION: This is
      the first report ever on the colon cancer-related signatures of anti-TF antibody
      diversity which show diagnostic potential, including in early cancer, and
      prognostic value. The hypersialylation of TF-specific antibodies appeared to be a
      common phenomenon in cancer. The signatures may be used as non-invasive antibody
      based markers for colon cancer.

PMID- 29600974
TI  - Morphological features of doxorubicin-resistant Walker 256 carcinosarcoma and
      response of mast cells.
AB  - BACKGROUND: The mechanisms of drug resistance of cancer have not been yet
      elucidated in details. Recently, the role of mast cells (MCs) in the development
      of drug resistance has been brought in the limelight. The aim of the study was to
      examine the morphological features of doxorubicin (DOX)-resistant Walker 256
      carcinosarcoma and to assess the response of MCs and histamine content in these
      cells in relation to the development of resistance to DOX as well as in DOX
      resistant tumors. MATERIALS AND METHODS: The DOX resistance was induced by serial
      passages of Walker 256 carcinosarcoma in rats in the setting of DOX treatment in
      vivo. MCs in tumors were detected in the sections by staining with Toluidine Blue
      O. Histamine content in MCs stained with solution of Water Blue-Orcein was
      assessed by Astaldi semiquantitative method taking into account different
      staining intensity. RESULTS: Formation of DOX resistance in the course of serial
      passages of Walker 256 carcinosarcoma was accompanied by the increase in the
      number of MCs in tumors and histamine content. Nevertheless, in tumors with
      phenotype of complete DOX resistance the number of histamine-containing MCs
      decreased to the same level as in tumors of the original strain that are DOX
      sensitive. CONCLUSION: MCs are involved in formation of DOX resistance in Walker
      256 carcinosarcoma.

PMID- 29600975
TI  - Highly activated carbon enterosorbent mediates the suppression of paraneoplastic
      syndrome associated with Lewis lung carcinoma in mice.
AB  - AIM: To investigate the effect of enterosorption on the development of
      paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). MATERIALS AND
      METHODS: The study was performed on male S57/VL6 mice with transplanted LLC. As
      an enterosorbent, highly activated powder fraction of HSGD was administered per
      os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after
      tumor cell transplantation. Analysis of hemo- and myelograms, morphological
      alterations in vital organs, the activities of catalase and superoxide dismutase,
      biochemical analysis of blood and quantitative analysis of hydroperoxides,
      malonic dialdehyde, advanced oxidation protein products was carried out by
      standard methods after completing the course of enterosorption. Ligand loading of
      blood plasma proteins was estimated by the method of differential scanning
      microcalorimetry. RESULTS: Administration of enterosorbent resulted in inhibition
      of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05).
      Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement
      of mitotic activity took place after enterosorbent administration. Red cell
      lineage indices and bone marrow cellularity remained unaltered. After
      enterosorption session, the studied biochemical indices of peripheral blood
      evidenced on decreasing the endogenous intoxication and oxidative stress levels,
      improving the functional state of kidneys, increasing the resistance of
      erythrocyte membranes and lowering the ligand loading of blood plasma transport
      proteins. Morphological structure of kidneys and liver confirmed significant
      positive effect of enterosorption. The data of morphologic examination of gastric
      fundus, small intestine, and large bowel slides after 2-week administration of
      enterosorbent showed its high safety and proper evacuation from intestine.
      CONCLUSION: The two-week long enterosorption session in mice with LLC caused the
      suppression of tumor growth and metastasis, normalization of bone marrow
      hemopoiesis. Enterosorption exerted a positive influence on the structural
      morphologic indexes and regenerative potential of kidneys and liver, mitigated
      manifestations of oxidative stress, decreased the level of endogenous
      intoxication, promoted deliganding of albumin molecule and deloading of
      erythrocyte membranes.

PMID- 29600976
TI  - Impact of endostatin gene therapy on myeloid-derived suppressor cells from a
      metastatic renal cell carcinoma.
AB  - AIM: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived
      suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC).
      MATERIALS AND METHODS: Balb/C mice bearing orthotopic Renca tumors were treated
      with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in
      vivo experiment, plasma and tissue lung samples were collected. Plasma ES and
      granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and
      Milliplex, respectively. Quantification of CD11b+Gr-1+ cells and their subsets
      was performed by flow cytometry. Reactive oxygen species (ROS) production was
      measured in CD11b+Gr-1+ MDSC using the DCFDA marker by flow cytometry. RESULTS:
      Metastatic RCC (mRCC) induced expansions of CD11b+Gr-1+ MDSC and promoted
      accumulation of these cells and their subtypes in lymphoid organ and metastases.
      ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor
      microenvironment, reflecting the reduced metastatic accumulation of CD11b+Gr-1+
      MDSC in the lungs. However, the therapy was selective for granulocytic cells,
      thus reducing the production of ROS. CONCLUSION: These findings confirm the
      expansion of MDSC during metastatic progression of RCC and indicate the important
      role of ES in reducing MDSC and possible use of ES therapy in combined anticancer
      treatment.

PMID- 29600978
TI  - Symposium and Summer School "Fundamental principles of cancer biotherapy".

PMID- 29600977
TI  - Characterization of the cytotoxic effects of the combination of cisplatin and
      flavanol (-)-epicatechin on human lung cancer cell line A549. An isobolographic
      approach.
AB  - BACKGROUND: Among malignancies, lung cancer is a leading cause of death. Platinum
      based therapeutic compounds used to treat lung cancer have not been able to
      increase the survival of patients and such compounds have a high incidence of
      adverse and toxic effects. It has been proposed that flavonoids such as catechins
      may significantly reduce the risk of developing cancer, alongside with other
      health benefits. The aim of this work was to determine the effect of (-)
      epicatechin, the main flavanol found in cocoa, on the proliferation of the lung
      non-small cell adenocarcinoma cancer cell line A549, and to determine its effects
      when added simultaneously with cisplatin. MATERIALS AND METHODS: Concentration
      response curves for cisplatin and epicatechin were obtained, inhibitory
      concentrations calculated and an isobolographic analysis was then performed.
      RESULTS: We found that epicatechin has a concentration-dependent inhibitory
      effect on proliferation of tumor cells and the isobolographic analysis reveals
      that the effect of its combination with cisplatin is synergistic. It was also
      observed that epicatechin promotes cell death by apoptosis. CONCLUSIONS:
      Epicatechin might be considered for future studies to explore its possible use as
      coadjuvant in cisplatin-based treatments.

PMID- 29600979
TI  - A long survival of a patient with brain metastasis of unknown site of the primary
      tumor.
AB  - Eighty percent of brain metastases (BM) are diagnosed in patients with known
      primary site of cancer. BM of unknown primary represents a difficult diagnosis.
      In up to 15% of patients with BM, the site of the primary tumor will not be
      detected despite investigations. The prognosis of this entity is very poor. We
      report here a case of a long survival of a patient with brain metastasis of
      unknown primary. The conclusion that can be drawn is that within BM of unknown
      primary exist patients with a very good prognosis that must be collected and
      published in order to base recommendations.

PMID- 29600980
TI  - Mediastinal yolk sac tumor infiltrating the heart.
AB  - BACKGROUND: As a rare tumor, yolk sac tumor is a type of neoplasm that appears
      like the yolk sac, extraembryonic mesenchyme, and allantois. The mediastinum is
      the second most frequent area after the gonadal area. CASE REPORT: We present an
      extremely rare case of 15 years old boy with mediastinal yolk sac tumor. The boy
      came with the chief complaint of swelling of the neck and face. Computed
      tomography scan of the chest revealed bulky mass with a cystic component that
      infiltrated the heart. The diagnosis of mediastinal yolk sac tumor was made after
      core needle biopsy. Histopathologic analysis revealed tumor mass with solid and
      microcystic structure and pleomorphic nucleus within the tumor cells. Laboratory
      finding showed elevated serum alpha-fetoprotein level reaching more than 8000
      ng/ml. Echocardiography revealed a mass in the right atrium. The patient
      condition was rapidly deteriorated due to his vena cava superior syndrome.
      Unfortunately, the patient died two days after diagnosis and we did not have the
      chance to do the therapy. CONCLUSION: Mediastinal yolk sac tumor is a rare
      malignancy that requires comprehensive management. The diagnosis should be made
      based on histopathological findings with the addition of thoracic computer
      tomography scan to assess the degree of infiltration to surrounding organ. A life
      threatening condition such as vena cava superior syndrome should be assessed
      promptly to allow for immediate treatment.

PMID- 29600981
TI  - Effect of cytostatic agents on expression levels of human beta-defensins-1-4 in
      A431 and MCF-7 cell lines.
AB  - : The aim of the study was to analyze an effect of cytostatic agents of different
      mechanism of action on expression levels of human beta-defensins-1-4 (hBD-1-4) in
      cultured human cancer cell lines. MATERIALS AND METHODS: Expression levels of hBD
      1-4 mRNA were assessed using qPCR in human epidermoid carcinoma A431 cells and
      human breast adenocarcinoma MCF7 cells treated with cisplatin, methotrexate,
      doxorubicin or vincristine at the IC20 concentrations. RESULTS: The cytostatic
      agents with different mechanisms of action affected differently expression of
      hBDs, dependent on the cell line. Mostly, cytostatic agents suppressed
      significantly expression of hBDs. In contrast, vincristine caused significant up
      regulation of hBD-1 (12 fold, p < 0.05) and hBD-4 (2 fold, p < 0.05) in MCF7, and
      doxorubicin significantly enhanced expression of hBD-3 (2 fold, p < 0.05) and hBD
      4 (> 10 fold, p < 0.05) in A431 cells. CONCLUSION: The results of this pilot
      study show that expression levels of hBD-1-4 may be altered upon treatment with
      cytostatic agents depending on nature of cells.

PMID- 29600982
TI  - Variant of rare Hermansky - Pudlak syndrome associated with granulomatous
      colitis: diagnostics, clinical course and treatment.
AB  - AIM: To study the relationship between the genotype and the phenotype in the
      patients with Hermansky - Pudlak syndrome (HPS) associated with granulomatous
      colitis; to monitor clinical course of the disease for adequate treatment, cancer
      surveillance and genetic counseling. MATERIALS AND METHODS: The diagnosis of HPS
      is established by physical examination, chest X-ray, computed tomography,
      endoscopic examination with biopsy, and laboratory tests, including histology,
      baseline laboratory blood, urine and feces tests, determination of ASCA-C and
      ANCA antibodies using an ELISA. Molecular genetic testing for HPS gene mutations,
      R702W, G908R, L1007fs and P268S mutations in NOD2 gene, and TaqI variant of the
      VDR gene were carried out. RESULTS: We report 2 cases of HPS from unrelated
      families. Both were complicated by inflammatory bowel disease with pathologic
      features of Crohn's disease refractory to antibiotics and corticosteroids. One
      patient (family 1) with Ashkenazi Jewish ancestry had pathogenic variant of the
      HPS-4 gene in exon 8, mutation P268S of NOD2 genes and "Tt" genotype of TaqI
      variant of the VDR gene. Another patient (family 2) carried two mutations P268S
      and G908R of NOD2 gene, and had a large paraovarian cyst diagnosed. No consistent
      success with the standard medical therapy, used for treating granulomatous
      colitis, associated with HPS, in presented cases was achieved. Patients needed
      surgical interventions at a young age and a long-term surveillance of the
      probable development of tumors and other complications. Azathioprine at 2
      mg/kg/day and mesalazine 3 g/day were used with some positive effect for
      prevention of Crohn's disease postoperative recurrence. CONCLUSION: The
      occurrence of perianal lesions, the histopathological findings and the results of
      the molecular genetic analysis confirmed the mutations P268S and G908R of NOD2
      gene in these cases suggest that HPS was truly associated with Crohn's disease
      variant with early onset and severe course. The search for the molecular causes
      of the disease in some individuals may help in the development of new therapeutic
      and surgical approaches, as well in the improvement of understanding of
      premalignant inflammatory conditions in a large bowel.

PMID- 29600983
TI  - Sensitivity to 4-hydroxyestradiol and DNA repair efficiency in peripheral blood
      lymphocytes of endometrial cancer patients.
AB  - BACKGROUND: The development of hormone-dependent cancers, including endometrial
      carcinomas, in great part may be mediated by the genotoxic effects of estrogen
      metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most
      prominent DNA-damaging properties. It is assumed that the individual sensitivity
      to the 4OHE2 may determine the predisposition to endometrial cancer (ES). AIM: To
      analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to
      the 4OHE2 and to evaluate the repair efficiency of 4OHE2-induced DNA damage.
      MATERIALS AND METHODS: The study was performed on the PBLs of 53 EC patients and
      20 healthy women. The level of DNA damage was measured using the comet assay and
      was expressed as % tail DNA. The DNA repair efficiency (%) was evaluated by
      determining the ratio between the amount of repaired DNA damage and the level of
      4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2. RESULTS:
      In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 +/- 2.2%
      tail DNA) and lower DNA repair efficiency (34.0 +/- 4.5%) was observed compared
      to PBLs of healthy women (22.3 +/- 2.3% tail DNA and 48.8 +/- 4.5%,
      respectively). PBLs of EC patients with deep tumor invasion of myometrium were
      characterized by more prominent decrease of DNA repair than those with less
      invasive tumor (< 1/2 of myometrium) (20.9 +/- 7.8 and 43.7 +/- 6.7%,
      respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs
      of EC patients with a family history of cancer compared to this parameter in
      patients with sporadic tumors (20.9+/-7.8 and 47.1 +/- 5.5%, respectively).
      CONCLUSION: The PBLs of EC patients are characterized by increased sensitivity to
      the genotoxic effect of 4OHE2 and reduced repair efficiency regarding 4OHE2
      induced DNA damage. A lower level of DNA repair is observed in EC patients with
      deep tumor myometrial invasion and a family history of cancer.

PMID- 29600984
TI  - Clinical implications of p53 alterations in oral cancer progression: a review
      from India.
AB  - p53 plays a central role in prevention of normal cell from the development of the
      malignant phenotype. Somatic alterations (mutations, loss of heterozygosity,
      deletions) in p53 are a hallmark of most human cancers and cause defects in
      normal p53 function. However, in the tumors harboring wild-type p53, there are
      alterations in the regulation of the p53. Thus, understanding why p53 is unable
      to perform its role as a tumor suppressor in these wild-type tumors is very
      crucial. Germ-line polymorphisms in p53 are also anticipated to cause measurable
      disturbance in p53 function. Over-expression as well as polymorphic variants of
      MDM2 might have effects on cancer development. In addition, degradation of p53 by
      E6 protein of high risk human papillomavirus is also suggested as one of the
      mechanisms which attenuate p53 responses in oral carcinogenesis. p53 has also
      been demonstrated to mediate cellular responses upon various DNA damaging cancer
      therapies, importantly, apoptosis. These responses have been implicated in an
      individual's ability to respond to these cancer therapies. Thus, exploring
      mechanisms by which normal function of p53 is affected in the comprehensive way
      in oral cancer might aid in the identification of tumor characteristics,
      prognosis and thus in the development of a new approach to treat the oral cancer.

PMID- 29600985
TI  - Role of components of microRNA machinery in carcinogenesis.
AB  - MicroRNAs (miRNAs) are a broad class of non-coding RNAs nearly 21 nucleotides
      length, which play crucial functions in post-transcriptional gene regulation.
      These molecules are associated with many developmental and cellular processes in
      eukaryotic organisms. Current investigation has reported major factors
      contributing to miRNA biogenesis and has constituted basic principles of miRNA
      function. More recently, it was confirmed that various miRNAs are clearly
      implicated in human malignancies, such as lung, breast, ovarian, bladder, colon
      cancer and other kinds of carcinoma. In addition, dysregulation in the miRNA
      machinery elements such as Dicer, Drosha, DGCR8, Argonaut, and TRBP could be
      involved in the progress of many tumor types. The purpose of the current review
      was to compile growing information besides how miRNA biogenesis and gene
      silencing are modified to develop cancer.

PMID- 29600986
TI  - Molecular-genetic models for prognosis of development of tumors of reproductive
      system in women with family history of cancer.
AB  - AIM: To develop a prognostic molecular genetic model for assessing the risk of
      development of benign and malignant tumors of female reproductive organs (FRO) in
      patients from cancer-affected families. PATIENTS AND METHODS: The work presents
      the data on a comprehensive clinical examination of 210 women (90 patients with
      FRO cancer with aggregation of tumor pathology in families, 65 patients with
      benign pathology of FRO from cancer-affected families, 55 women - control group
      of healthy women without family history of cancer). Clinical genealogical
      analysis, morphological examination of tumors and molecular genetic studies of
      genomic DNA from peripheral blood and tumors were carried out. RESULTS: It was
      established that in the families of patients with benign and malignant pathology
      of FRO, malignant tumors associated with Lynch II syndrome are observed. Based on
      the analysis of detected ESR-1, CYP 2D6*4 and mutations in BRCA1/2 genes in
      cancer patients and in patients with benign pathology, molecular genetic models
      have been developed to assess the individual risk of development of benign and
      malignant tumors of FRO. It has been established that these molecular genetic
      models and combinations of gene mutations and gene polymorphisms (SNP) by the
      intergene interaction that was analyzed, were found to be reliable in assessing
      the risk of benign and malignant pathology of the mammary gland and ovary.
      CONCLUSIONS: The model, which included the polymorphic variants of the
      T397C(ESR1)/CYP 2D6*4 genes was of the best predictive accuracy for the
      evaluation of the risk of benign tumors of the FRO (71.68%) and the highest
      reliability (p < 0.001). At the same time, all identified models of intergene
      interaction in the development of malignant pathology of FRO were reliable,
      prognostically significant with high reproduction and almost identical accuracy
      (65.00-68.23%). The obtained results indicate a high informativeness of such
      molecular genetic indices as the polymorphism of ESR1 and CYP 2D6*4 genes and
      mutations in BRCA1/2 genes to assess the risk of benign or malignant tumors of
      FRO in families of patients with family history of cancer.

PMID- 29600987
TI  - The use of optical coherence tomography angiography for detecting choroidal
      neovascularization, compared to standard multimodal imaging.
AB  - PurposeTo assess OCT angiography (OCTA) effectiveness at detecting choroidal
      neovascularization (CNV) in cases of suspected neovascular age related macular
      degeneration (nAMD), chronic central serous retinopathy (cCSR) and pathological
      myopia compared to FFA and how it compares to a multimodal approach (OCT, FFA and
      ICGA) for detecting the vascular network.MethodsThis was a retrospective
      observational cohort study of patients who had clinical and/or OCT findings
      suggestive of CNV, having further investigation with FFA, with or without ICG,
      and had same day OCTA using the Heidelberg Spectralis OCT2 beta angiography
      module. Multimodal imaging interpretation was compared to OCTA images. OCTA
      images were also analysed for inter-rater reliability (using kappa statistic).
      The diagnostic accuracy of OCTA was compared to FFA (using Cochran's Q, p<0.05).
      OCTA was also compared to a multimodal approach in defining a vascular
      network.ResultsOverall sensitivity of OCTA compared to FFA was 71% and
      specificity of 81% (p=0.108). Subgroup analysis for OCTA vs FFA for detecting
      classic nAMD/type II CNV sensitivity was 100% and specificity of 76% (p<0.05).
      OCTA vs FFA for detecting occult nAMD/type-I CNV sensitivity was 47% and
      specificity of 76%, (p=0.248). OCTA was better than FFA at defining a vascular
      network overall, when OCT was suspicious (59% vs 49%).ConclusionsOCTA was better
      at detecting classic nAMD/type II CNV compared to FFA and for defining a vascular
      network in nAMD compared to FFA and ICGA. It was able to aid in making the
      diagnosis in cases where evidence of CNV was uncertain following FFA/ICGA.

PMID- 29600988
TI  - Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".

PMID- 29600989
TI  - Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".

PMID- 29600990
TI  - Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".

PMID- 29600991
TI  - Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".

PMID- 29600992
TI  - Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".

PMID- 29600993
TI  - Ultra-sensitive lithium niobate thermometer based on a dual-resonant whispering
      gallery-mode cavity.
AB  - We exploit the strong polarization dependence of the thermooptic coefficients in
      a lithium niobate whispering-gallery-mode resonator to create a self-referenced
      thermometer. An unprecedented temperature sensitivity of 3.0 GHz/K in the
      frequency difference between modes of orthogonal polarizations is demonstrated.
      In order to lock the lasers to the mode resonances, we use a simple intracavity
      phase modulation approach that provides for superbly low frequency instability.
      We demonstrate a record room-temperature thermometer detectivity of 40 nK with 1
      s of averaging time. Simulations based on the fluctuation-dissipation theorem are
      performed to calculate the fundamental thermorefractive noise, showing that the
      detectivity could be improved with reduced laser-locking instabilities.

PMID- 29600994
TI  - Anomalous refraction of a low divergence monochromatic light beam in a
      transparent slab.
AB  - An exact formulation for the propagation of a monochromatic wave packet impinging
      on a transparent, homogeneous, isotropic, and parallel slab at oblique incidence
      is given. Approximate formulas are derived for low divergence light beams. These
      formulas show the presence of anomalous refraction phenomena at any slab
      thickness, including negative refraction and flat lensing effects, induced by
      reflection at the rear face.

PMID- 29600995
TI  - Three-dimensional super-resolved live cell imaging through polarized multi-angle
      TIRF.
AB  - Measuring three-dimensional nanoscale cellular structures is challenging,
      especially when the structure is dynamic. Owing to the informative total internal
      reflection fluorescence (TIRF) imaging under varied illumination angles, multi
      angle (MA) TIRF has been examined to offer a nanoscale axial and a subsecond
      temporal resolution. However, conventional MA-TIRF still performs badly in
      lateral resolution and fails to characterize the depth image in densely
      distributed regions. Here, we emphasize the lateral super-resolution in the MA
      TIRF, exampled by simply introducing polarization modulation into the
      illumination procedure. Equipped with a sparsity and accelerated proximal
      algorithm, we examine a more precise 3D sample structure compared with previous
      methods, enabling live cell imaging with a temporal resolution of 2 s and
      recovering high-resolution mitochondria fission and fusion processes. We also
      shared the recovery program, which is the first open-source recovery code for MA
      TIRF, to the best of our knowledge.

PMID- 29600996
TI  - Tunable light absorbance by exciting the plasmonic gap mode for refractive index
      sensing.
AB  - The tunable and narrowband optical response from the surface plasmon resonances
      usually requires periodic metal nanostructures; however, it is usually expensive
      and challenging to construct such macroscale and defect-free devices. Herein, we
      make it possible to obtain a characteristic and sharp absorbance via exciting the
      plasmonic gap mode, which can be obtained in a large-area sample prepared with
      relatively low cost. The resonant wavelength can be tuned via changing the bottom
      facet area of the top structured metal or the spacer thickness. Furthermore, we
      design the hexagonal arrangement gold microholes atop the gold continuous film
      with a spacer, which possesses a sharp reflectance dip from the intense plasmonic
      gap mode. Numerical calculations show that the resonant wavelength is linearly
      changed with the varying environmental refractive index (RI). The sensitivity is
      up to ~1287  nm per RI unit, and the figure of merit for an RI sensor is over
      300.

PMID- 29600997
TI  - High-efficiency ultrafast Tm-doped fiber amplifier based on resonant pumping.
AB  - We demonstrated a high-efficiency ultrafast Tm-doped fiber amplifier based on a
      resonant pumping technique. A continuous-wave fiber laser at 1940 nm was employed
      as the pump laser. The slope efficiency of the resonantly pumped pulsed Tm-doped
      fiber amplifier reached 87% with respect to the launched pump power. The maximum
      average output power reached 40 W when the launched pump power was 53 W. The
      repetition rate and the pulse duration of the output pulses from a fiber
      amplifier were 248 MHz and 129 ps, respectively. The corresponding peak power was
      1.25 kW, and the pulse energy was 161.3 nJ. To the best of our knowledge, this is
      the first demonstration of a resonant pumping enabled high-power high-efficiency
      ultrafast fiber laser operating at a 2 MUm band.

PMID- 29600998
TI  - Mode measurement of few-mode fibers by mode-frequency mapping.
AB  - Since few-mode fibers (FMFs) have great potential as the new transmission media
      for optical communications, the ability to distinguish different fiber modes is
      essential. Most of the traditional schemes do not yield phase information, or are
      limited by beam size and mechanical requirements. Here, a method is presented to
      analyze the mode distribution of FMFs. The fiber modes are mapped to different
      frequencies by using dynamic spatial phase masks. The complex amplitudes at these
      frequencies indicate the amplitudes and phases of the fiber modes. The method can
      extract not only the amplitude distribution, but also the phase distribution of
      the fiber modes, and no other assisted light is needed.

PMID- 29600999
TI  - Polarization-controlled orbital angular momentum switching in nonlinear wave
      mixing.
AB  - We demonstrate polarization-controlled switching of the orbital angular momentum
      (OAM) transfer in nonlinear wave mixing. By adjusting the input beam geometry, we
      are able to produce a three-channel orbital OAM, with arbitrary topological
      charges simultaneously generated and spatially resolved in the second-harmonic
      wavelength. The use of path and polarization degrees of freedom allows nearly
      perfect optical switching between different OAM operations. These results are
      supported by a theoretical model showing very good agreement with the
      experiments.

PMID- 29601000
TI  - Fiber fuse in chalcogenide photonic crystal fibers.
AB  - We observe fiber fuse in tapered GeAsSe photonic crystal fibers (PCF) at around 7
      MW/cm2 of intra-core intensity. Vertically cleaved facets from the un-tapered
      regions and the tapered regions were imaged. The images show shallow voids of
      different shapes confined to the fiber core. After longitudinally polishing a
      segment of the PCF, we imaged the PCF internal structure's top view, revealing
      the fuse voids' geometries and periodicity. In addition, fiber fuse was
      terminated in one PCF sample by a fast laser shutdown, hence saving a small
      segment from catastrophic damage. Four-wave-mixing was performed on this
      transmissive segment to estimate the dispersion. The results yielded an evident
      hole-pitch ratio change after fiber fuse. To our knowledge, this is the first
      report of fiber fuse on non-silica glass fibers and the first study of its
      aftermath on this un-destroyed segment of PCFs.

PMID- 29601001
TI  - Time-of-flight detection of femtosecond laser pulses for precise measurement of
      large microelectronic step height.
AB  - We propose and demonstrate a new method which employs time-of-flight detection of
      femtosecond laser pulses for precise height measurement of large steps. By using
      time-of-flight detection with fiber-loop optical-microwave phase detectors,
      precise measurement of large step height is realized. The proposed method shows
      uncertainties of 15 nm and 6.5 nm at sampling periods of 40 ms and 800 ms,
      respectively. This method employs only one free-running femtosecond mode-locked
      laser and requires no scanning of laser repetition rate, making it easier to
      operate. Precise measurements of 6 MUm and 0.5 mm step heights have been
      demonstrated, which show good functionality of this method for measurement of
      step heights.

PMID- 29601002
TI  - Influence of the shielding effect on the formation of a micro-texture on the
      cermet with nanosecond pulsed laser ablation.
AB  - The degree of laser pulse overlapping in a laser scanning path has a significant
      impact on the ablation regime in the laser machining of a micro-texture. In this
      Letter, a nanosecond pulsed laser is used to prepare the micro-scaled groove on
      WC-8Co cermet under different scanning speeds. It is observed that as the
      scanning speed increases, the ablated trace morphology in the first scanning pass
      transits from a succession of intermittent deep dimples to the consecutive
      overlapped shallow pits. The test result also indicates that ablated trace
      morphology with respect to the low scanning speed stems from a plume shielding
      effect. Moreover, the ablation regime considering the shielding effect in micro
      groove formation process is clarified. The critical scanning speed that can
      circumvent the shielding effect is also summarized with respect to different
      laser powers.

PMID- 29601003
TI  - Mechanism of large optical nonlinearity in gold nanoparticle films.
AB  - The Z-scan technique, using femtosecond (fs) laser pulses at 1480 nm laser
      pulses, was used to measure the nonlinear optical properties of gold (Au)
      nanoparticle (NP) films made by both nanosecond (ns) and fs pulsed laser
      deposition (PLD) in vacuum. At irradiance levels of 1*1012  Wm-2, the ns-PLD
      films displayed induced absorption with beta=4*10-5  mW-1, and a negative lensing
      effect with n2=-4.7*10-11  m2 W-1 with somewhat smaller values for the fs-PLD
      films. These values of n2 imply an unphysically large change in the real part of
      the refractive index, demonstrating the need to take account of nonlinear changes
      of the Fresnel coefficients and multiple beam interference in Z-scan measurements
      on nanoscale films. Following this approach, the Z-scan observations were
      analyzed to determine the effective complex refractive index of the NP film at
      high irradiance. It appears that at high irradiance the NP film behaves as a
      metal, while at low irradiance it behaves as a low-loss dielectric. Thus, it is
      conjectured that, for high irradiance near the waist of the Z-scan laser beam,
      laser driven electron tunneling between NPs gives rise to metal-like optical
      behavior.

PMID- 29601004
TI  - Curving h-BN thin films can create extra phonon polariton modes.
AB  - Hexagonal boron nitride (h-BN) thin films support volume-confined phonon
      polariton modes within the bulk material as well as surface-confined modes at the
      edges of thin films. In this Letter, we theoretically investigate the phonon
      polaritons in curved h-BN thin films. One-dimensional guided phonon polariton
      modes are found, which are caused by the curved geometry and do not exist in
      extended flat films. These modes are guided along a specific direction with
      relatively low propagation losses. So far, one-dimensional guided phonon
      polariton modes have only been proposed in nanowire and nanoribbon structures.
      Our study offers another way with the advantage of keeping the h-BN film intact,
      which can avoid huge scattering losses due to the structural defects. These
      investigations may offer an easy and robust approach toward phonon-polariton
      based nanophotonic circuitry.

PMID- 29601005
TI  - Resource-theoretic approach to vectorial coherence.
AB  - We propose a formal resource-theoretic approach to assess the coherence between
      partially polarized electromagnetic fields. From this framework, we identify two
      resource theories for the vectorial coherence: polarization-sensitive coherence
      and polarization-insensitive coherence. For each theory, we find the set of
      incoherent states and a class of operations that preserve this set (i.e., the
      incoherent operations). Both resource theories are endowed with a certain
      preorder relation that provides a hierarchy among the coherence-polarization
      states; thus, a necessary condition to consider in deciding whether a quantity is
      proper to measure the vectorial coherence is that it respects such a hierarchy.
      Finally, we examine most previously introduced coherence measures from this
      perspective.

PMID- 29601006
TI  - Spectral interpretation of Talbot self-healing effect and application to optical
      arbitrary waveform generation.
AB  - The Talbot effect has the intrinsic capability of mitigating the effects of
      grating imperfections. Here we investigate, in the frequency domain, the
      influence of an imperfect grating on the Talbot images. In particular, we show
      that for specific propagation distances, the spectra of the individual Talbot
      images are directly related to the envelope of the grating transmission function,
      mapped in the spectral domain. This novel space-to-frequency mapping property
      enables us to describe the capability of image restoration (or self-healing) of
      the Talbot effect, in terms of spectral filtering. The transposition of this
      effect from the spatial to the temporal domain offers promising possibilities for
      the spectral shaping of optical waveforms.

PMID- 29601007
TI  - Watt-level dysprosium fiber laser at 3.15  MUm with 73% slope efficiency.
AB  - Rare-earth-doped fiber lasers are emerging as promising high-power mid-infrared
      sources for the 2.6-3.0 MUm and 3.3-3.8 MUm regions based on erbium and holmium
      ions. The intermediate wavelength range, however, remains vastly underserved,
      despite prospects for important manufacturing and defense applications. Here, we
      demonstrate the potential of dysprosium-doped fiber to solve this problem, with a
      simple in-band pumped grating-stabilized linear cavity generating up to 1.06 W at
      3.15 MUm. A slope efficiency of 73% with respect to launched power (77% relative
      to absorbed power) is achieved-the highest value for any mid-infrared fiber laser
      to date, to the best of our knowledge. Opportunities for further power and
      efficiency scaling are also discussed.

PMID- 29601008
TI  - Laser stabilization with a frequency-to-voltage chip for narrow-line laser
      cooling.
AB  - We use integrated circuit-based frequency-to-voltage conversion of a frequency
      comb beat signal as the means for laser frequency stabilization that is suitable
      for narrow-line laser cooling. The method is compared to an atomic beam lock
      where the laser frequency instability for the new scheme shows an improvement of
      2 orders of magnitude at sub-1 s and grants a lock-capture range that is
      approximately 30 times greater. We employ the locking method on a 1111.6 nm laser
      that is frequency doubled and used in a dual-wavelength magneto-optical trap for
      Yb171 atoms, producing atomic cloud temperatures of ~20  MUK.

PMID- 29601009
TI  - Polarization-insensitive four-channel coarse wavelength-division (de)multiplexer
      based on Mach-Zehnder interferometers with bent directional couplers and
      polarization rotators.
AB  - A polarization-insensitive four-channel coarse wavelength-division multiplexing
      (CWDM) (de)multiplexer based on Mach-Zehnder interferometers is proposed and
      demonstrated. By utilizing the bent directional couplers and the polarization
      rotators, the CWDM (de)multiplexer could work for both transverse electric and
      transverse magnetic polarizations. The measurement results of the fabricated
      devices show that the 1-dB bandwidth is ~15  nm for dual polarizations, and the
      polarization dependent losses are <~0.5  dB for all four channels.

PMID- 29601010
TI  - Flying particle microlaser and temperature sensor in hollow-core photonic crystal
      fiber.
AB  - Whispering-gallery mode (WGM) resonators combine small optical mode volumes with
      narrow resonance linewidths, making them exciting platforms for a variety of
      applications. Here we report a flying WGM microlaser, realized by optically
      trapping a dye-doped microparticle within a liquid-filled hollow-core photonic
      crystal fiber (HC-PCF) using a CW laser and then pumping it with a pulsed
      excitation laser whose wavelength matches the absorption band of the dye. The
      laser emits into core-guided modes that can be detected at the endfaces of the HC
      PCF. Using radiation forces, the microlaser can be freely propelled along the HC
      PCF over multi-centimeter distances-orders of magnitude farther than in previous
      experiments where tweezers and fiber traps were used. The system can be used to
      measure temperature with high spatial resolution, by exploiting the temperature
      dependent frequency shift of the lasing modes, and may also permit precise
      delivery of light to remote locations.

PMID- 29601011
TI  - Local activation of surface and hybrid acoustic waves in optical microwires.
AB  - Elastic vibrations in subwavelength structures have gained importance recently in
      fundamental light-matter studies and various optoacoustic applications. Existing
      techniques have revealed the presence of distinct acoustic resonances inside
      silica microwires yet remain unable to individually localize them. Here, we
      locally activate distinct classes of acoustic resonances inside a tapered fiber
      using a phase-correlation distributed Brillouin method. Experimental results
      verify the presence of surface and hybrid acoustic waves at distinct fiber
      locations and demonstrate, to the best of our knowledge, the first distributed
      surface acoustic wave measurement. This technique is important for understanding
      properties of optoacoustic interactions and enabling designs of novel
      optomechanical devices.

PMID- 29601012
TI  - Photonics-enabled wideband microwave burst detection.
AB  - In this Letter, to the best of our knowledge, a novel wideband microwave burst
      detection system is realized by utilizing photonics-assisted wavelength and time
      division multiplexing, in conjunction with optical storage. Deploying a coherent
      electro-optical dual comb and a recirculating optical frequency shifter with
      ~1.28  MUs round-rip delay, the proof-of-concept experimental system demonstrates
      the interrogation of ~1  MUs radio frequency (RF) bursts with up to an 8 GHz
      bandwidth and arbitrary hopping pattern at 1 MHz resolution and a refresh rate of
      ~60  kHz using an 80 MHz RF detection unit. The proposed system can be easily
      upgraded to higher bandwidths and longer burst time apertures with suitable
      hardware.

PMID- 29601013
TI  - Digital chromatic dispersion pre-management enabled single-lane 112  Gb/s PAM-4
      signal transmission over 80  km SSMF.
AB  - We experimentally demonstrate single-lane 112 Gb/s four-level pulse-amplitude
      modulation signal transmission over 80 km standard single-mode fiber (SSMF) by
      digital chromatic dispersion (CD) pre-management. By theoretically investigating
      the interplay between CD and self-phase modulation (SPM) during the SSMF
      transmission, we identify that the SPM induced impairment can be optically
      mitigated by the residual positive CD of the SSMF link. Thanks to the digital CD
      pre-management for the purpose of both CD compensation and nonlinear impairment
      mitigation, a simplified Volterra filter equalizer is good enough to achieve bit
      error rate below the 7% hard-decision forward error correcting threshold.

PMID- 29601014
TI  - Sidelobe apodization in optical pulse compression reflectometry for fiber optic
      distributed acoustic sensing.
AB  - We demonstrate a technique to reduce the sidelobes in optical pulse compression
      reflectometry for distributed acoustic sensing. The technique is based on using a
      Gaussian probe pulse with linear frequency modulation. This is shown to improve
      the sidelobe suppression by 13 dB compared to the use of square pulses without
      any significant penalty in terms of spatial resolution. In addition, a 2.25 dB
      enhancement in signal-to-noise ratio is calculated compared to the use of
      receiver-side windowing. The method is tested by measuring 700 Hz vibrations with
      a 140  nepsilon amplitude at the end of a 50 km fiber sensing link with 34 cm
      spatial resolution, giving a record 147,058 spatially resolved points.

PMID- 29601015
TI  - Three-dimensional Dirac semimetal thin-film absorber for broadband pulse
      generation in the near-infrared.
AB  - In this Letter, the transient nonlinear absorption of three-dimensional (3D)
      topological Dirac semimetal Cd3As2 thin film was characterized in the near
      infrared band. By performing broadband pump-probe measurements, we experimentally
      proved that molecular beam epitaxy (MBE) grown Cd3As2 exhibits strong and tunable
      saturable absorption effects across 1-2 MUm. By further inserting the Cd3As2 film
      into the cavities of Tm- and Er-doped fiber lasers, we obtained stable mode
      locked operations at 1.96 and 1.56 MUm. Our results experimentally establish that
      Cd3As2 is a promising broadband saturable absorber (SA) for pulsed lasers in the
      infrared range.

PMID- 29601016
TI  - Critically phase-matched Ti:sapphire-laser-pumped deep-infrared femtosecond
      optical parametric oscillator based on CdSiP2.
AB  - We report a high-repetition-rate femtosecond optical parametric oscillator (OPO)
      for the deep-infrared (deep-IR) based on type-I critical phase-matching in CdSiP2
      (CSP), pumped directly by a Ti:sapphire laser. Using angle-tuning in the CSP
      crystal, the OPO can be continuously tuned across 7306-8329 nm (1201-1369  cm-1)
      in the deep-IR. It delivers up to 18 mW of idler average power at 7306 nm and >7 
      mW beyond 8000 nm at 80.5 MHz repetition rate, with the spectra exhibiting
      bandwidths of >150  nm across the tuning range. Moreover, the signal is tunable
      across 1128-1150 nm in the near-infrared, providing up to 35 mW of average power
      in ~266  fs pulses at 1150 nm. Both beams exhibit single-peak Gaussian
      distribution in TEM00 spatial profile. With an equivalent spectral brightness of
      ~5.6*1020photons s-1 mm-2 sr-10.1% BW-1, this OPO represents a viable alternative
      to synchrotron and supercontinuum sources for deep-IR applications in
      spectroscopy, metrology, and medical diagnostics.

PMID- 29601017
TI  - Grayness-dependent emission of dispersive waves from dark solitons in optical
      fibers.
AB  - We report the experimental observation of dispersive wave emission from gray
      solitons propagating in the normal dispersion region of an optical fiber. Besides
      observing for the first time, to the best of our knowledge, the emission of a
      dispersive wave from an isolated dark soliton, we show that the dispersive wave
      frequency and amplitude strongly depend on soliton grayness. This process can be
      explained by the higher-order dispersion contribution into the phase-matching
      condition and the grayness of the soliton. Numerical simulations and theoretical
      predictions are in good agreement with the experiments.

PMID- 29601018
TI  - Extreme electro-optic tuning of Bragg mirrors integrated in lithium niobate
      nanowaveguides.
AB  - Bragg reflectors (BRFs) are essential elements in optical telecommunication and
      sensing applications. Their miniaturization down to the sub-micron scale has been
      achieved in silicon-on-insulator chips. However, their tunability is limited only
      to thermal tuning. In order to achieve a faster and more practical tunability
      operation, here we report on electro-optically tunable BRFs with ~14  dB signal
      filtering on a lithium-niobate-on-insulator platform, while keeping sub-micron
      cross-sections. Due to the lithium niobate electro-optic properties and the
      chosen electrodes configuration, a Bragg tunability coefficient of 23.37+/-0.55 
      pm/V is achieved, which enhances ~33 times the tunability performance of state-of
      the-art BRFs.

PMID- 29601019
TI  - Coherently combined 16-channel multicore fiber laser system.
AB  - We present a coherently combined laser amplifier with 16 channels from a
      multicore fiber in a proof-of-principle demonstration. Filled-aperture beam
      splitting and combination, together with temporal phasing, is realized in a
      compact and low-component-count setup. Combined average power of up to 70 W with
      40 ps pulses is achieved with combination efficiencies around 80%.

PMID- 29601020
TI  - Approach for temperature-insensitive strain measurement using a dual-core As2Se3
      PMMA taper.
AB  - A temperature-insensitive strain sensor is proposed and demonstrated based on a
      dual-core As2Se3-polymethyl methacrylate (PMMA) taper. Longitudinal and
      transverse forces on the As2Se3 cores are induced by thermal
      expansion/contraction of the PMMA cladding due to an order of magnitude
      difference between the thermal expansion coefficients of As2Se3 and PMMA. At an
      optimal PMMA layer thickness, the wavelength shift caused by the thermally
      induced forces on the refractive index of the dual-core fiber cores
      counterbalances that caused by the thermally induced fiber length variation
      leading to temperature-insensitive transmission. Temperature-insensitive strain
      measurement over a temperature range from 30 degrees C to 40 degrees C is
      demonstrated in a dual-core As2Se3-PMMA fiber with an As2Se3 core diameter of
      0.61 MUm and a PMMA cladding diameter of 34.4 MUm. Thermally induced forces in
      hybrid fibers open the path towards the realization of novel sensors and devices
      that are immune to temperature fluctuations.

PMID- 29601021
TI  - Deuterated silicon nitride photonic devices for broadband optical frequency comb
      generation.
AB  - We report and characterize low-temperature, plasma-deposited deuterated silicon
      nitride films for nonlinear integrated photonics. With a peak processing
      temperature less than 300 degrees C, it is back-end compatible with complementary
      metal-oxide semiconductor substrates. We achieve microresonators with a quality
      factor of up to 1.6*106 at 1552 nm and >1.2*106 throughout lambda=1510-1600  nm,
      without annealing or stress management (film thickness of 920 nm). We then
      demonstrate the immediate utility of this platform in nonlinear photonics by
      generating a 1 THz free-spectral-range, 900 nm bandwidth modulation-instability
      microresonator Kerr comb and octave-spanning, supercontinuum-broadened spectra.

PMID- 29601022
TI  - Measurement of rotation speed based on double-beam self-mixing speckle
      interference.
AB  - A rotation speed measurement based on double-beam self-mixing speckle
      interference is presented. The self-mixing speckle signal is analyzed by a cross
      correlation algorithm. The experimental results show that, compared with the
      Doppler frequency shift method, the proposed method can measure high speed at a
      low sampling rate.

PMID- 29601023
TI  - Spin-optomechanical coupling between light and a nanofiber torsional mode.
AB  - Light that carries linear or angular momentum can interact with a mechanical
      object, giving rise to optomechanical effects. In particular, a photon can
      transfer its intrinsic angular momentum to an object when the object either
      absorbs the photon or changes the photon polarization, as in an action/reaction
      force pair. Here, we demonstrate resonant driving of torsional mechanical modes
      of a single-mode tapered optical nanofiber using spin angular momentum. The
      nanofiber torsional mode spectrum is characterized by polarimetry, showing narrow
      natural resonances (Q~2,000). By sending amplitude-modulated light through the
      nanofiber, we resonantly drive individual torsional modes as a function of the
      light polarization. By varying the input polarization to the fiber, we find the
      largest amplification of a mechanical oscillation (>35  dB) is observed when
      driving the system with light containing longitudinal spin on the nanofiber
      waist. These results present optical nanofibers as a platform suitable for
      quantum spin-optomechanics experiments.

PMID- 29601024
TI  - Broadband and high-efficiency vortex beam generator based on a hybrid helix
      array.
AB  - The vortex beam which carries the orbital angular momentum has versatile
      applications, such as high-resolution imaging, optical communications, and
      particle manipulation. Generating vortex beams with the Pancharatnam-Berry (PB)
      phase has drawn considerable attention for its unique spin-to-orbital conversion
      features. Despite the PB phase being frequency independent, an optical element
      with broadband high-efficiency circular polarization conversion feature is still
      needed for the broadband high-efficiency vortex beam generation. In this work, a
      broadband and high-efficiency vortex beam generator based on the PB phase is
      built with a hybrid helix array. Such devices can generate vortex beams with
      arbitrary topological charge. Moreover, vortex beams with opposite topological
      charge can be generated with an opposite handedness incident beam that propagates
      backward. The measured efficiency of our device is above 65% for a wide frequency
      range, with the relative bandwidth of 46.5%.

PMID- 29601025
TI  - Micro-hole drilling by tightly focused vector beams.
AB  - We demonstrated that azimuthally polarized beams offer high-speed laser micro
      hole drilling compared with radially and linearly polarized beams under a tight
      focusing condition. The speed was evaluated by piercing time by vector beams for
      several objective lenses with different numerical apertures (NAs). As a result,
      in the case of NA=0.63, the piercing time of an azimuthally polarized beam was
      2.4 to 3.2 times shorter than that of a linearly polarized beam for all materials
      tested. Surprisingly, for NA=0.85, the difference is expanded to about 7.7 times
      for copper. This indicates that the number of reflections on the side wall of the
      hole played a significant role to give rise to the difference in the piercing
      time, depending on the polarization of the light beam.

PMID- 29601026
TI  - Spectrally efficient digitized radio-over-fiber system with k-means clustering
      based multidimensional quantization.
AB  - We propose a spectrally efficient digitized radio-over-fiber (D-RoF) system by
      grouping highly correlated neighboring samples of the analog signals into
      multidimensional vectors, where the k-means clustering algorithm is adopted for
      adaptive quantization. A 30  Gbit/s D-RoF system is experimentally demonstrated
      to validate the proposed scheme, reporting a carrier aggregation of up to 40 100
      MHz orthogonal frequency division multiplexing (OFDM) channels with quadrate
      amplitude modulation (QAM) order of 4 and an aggregation of 10 100 MHz OFDM
      channels with a QAM order of 16384. The equivalent common public radio interface
      rates from 37 to 150  Gbit/s are supported. Besides, the error vector magnitude
      (EVM) of 8% is achieved with the number of quantization bits of 4, and the EVM
      can be further reduced to 1% by increasing the number of quantization bits to 7.
      Compared with conventional pulse coding modulation-based D-RoF systems, the
      proposed D-RoF system improves the signal-to-noise-ratio up to ~9  dB and greatly
      reduces the EVM, given the same number of quantization bits.

PMID- 29601027
TI  - 21 spatial mode erbium-doped fiber amplifier for mode division multiplexing
      transmission.
AB  - We experimentally demonstrate a 12-mode group (21 spatial mode) cladding-pumped
      few-mode erbium-doped fiber amplifier. The differential modal gain (DMG) is
      dramatically reduced by using the double cladding erbium-doped fiber (DC-EDF)
      with a refractive index trench structure, which helps to tightly confine all 21
      spatial modes in the core and to mitigate the bending loss. Our experimental
      results show that the DMG gain is about 3 dB when the average signal modal gain
      for all 12 mode groups is up to 15 dB across the C-band. Our method of using a DC
      EDF with a properly designed trench structure can be used to develop gain
      equalized few-mode amplifiers supporting more spatial modes.

PMID- 29601028
TI  - Integrated flexible-grid WDM transmitter using an optical frequency comb in
      microring modulators.
AB  - Advanced optical interconnects require high-speed links, which can be achieved by
      combining high channel rates with wavelength-division multiplexing (WDM). We
      report a multi-channel transmitter using cascaded microring modulators (MRMs) in
      silicon photonics. One MRM works as a flexible-grid optical comb generator, while
      the others work as channel modulators. With a single-wavelength laser input, we
      achieve flexible channel spacing (up to 25 GHz) with a tone-to-noise ratio above
      54 dB at low power consumption of less than 4.6 mW. We examine experimentally
      multi-channel transmission modulating data onto adjacent comb lines without
      significant signal crosstalk. This single-laser, flexible-grid WDM transmitter is
      a scalable solution: more comb lines can be obtained using uncoupled MRMs in a
      series. To the best of our knowledge, this is the first demonstration of
      monolithic integration of a comb generator and multi-channel modulators for ultra
      compact, power-efficient WDM photonic interconnects.

PMID- 29601029
TI  - Michelson mode selector for spectral range stabilization in a self-sweeping fiber
      laser.
AB  - We report on spectral range stabilization in a self-sweeping laser by adding a
      narrowband fiber Bragg grating (FBG) to the output mirror in the Michelson
      configuration. The effects of FBG reflectivity and optical path difference in the
      Michelson interferometer on the laser spectral dynamics are investigated.
      Optimization of the interferometer allows us to demonstrate broadband (over 16
      nm) self-sweeping operation and reduction of the start and stop wavelength
      fluctuations by two orders and one order of magnitude (~100 and 15 times) for
      start and stop bounds, respectively (down to several picometers). The proposed
      approaches significantly improve quality of the spectral dynamics and facilitate
      application of the self-sweeping lasers.

PMID- 29601030
TI  - High-efficiency 1064  nm nonplanar ring oscillator Nd:YAG laser with diode
      pumping at 885  nm.
AB  - We experimentally demonstrate a monolithic single-frequency nonplanar ring
      oscillator (NPRO) laser pumped by diode lasers from a thermally excited ground
      level directly into a metastable level of Nd3+:YAG gain medium. Continuous-wave
      output power of 4.54 W is obtained at 1064 nm with 7.6 W input at 885 nm, and the
      slope efficiency is 76.9% at incident power above 2 W. Compared with the 50.7%
      slope efficiency obtained using 808 nm pumping for the same NPRO, this direct
      pumping shows a potential advantage in improving the energy efficiency. The
      observation is consistent with an analysis of the heat generation in both direct
      and traditional pumping schemes. The power fluctuation is measured to be within
      0.8% at 3 W output during a 10 h period.

PMID- 29601031
TI  - All-fiber gas sensor with intracavity photothermal spectroscopy.
AB  - We present an all-fiber intracavity photothermal (IC-PT) spectroscopic gas sensor
      with a hollow-core photonic bandgap fiber (HC-PBF) gas cell. The gas cell is
      placed inside a fiber-ring laser cavity to achieve higher laser light intensity
      in the hollow core and hence higher PT modulation signal. An experiment with a
      0.62-m-long HC-PBF gas cell demonstrated a noise equivalent concentration of 176
      ppb acetylene. Theoretical modeling shows that the IC-PT sensor has the potential
      of achieving sub-ppb (parts-per-billion) acetylene detection sensitivity.

PMID- 29601032
TI  - Spectral shifts of stimulated Rayleigh-Mie scattering in Ag nanoparticle
      colloids.
AB  - Stimulated Rayleigh-Mie scattering (SRMS) in two-photon absorption liquids is
      realized by a Fourier-transform-limited pulsed Nd-glass laser. For the first
      time, to the best of our knowledge, we have measured anti-Stokes spectral shifts
      of SRMS in toluene and hexane colloids of Ag nanoparticles, as well as in pure
      toluene. These values appreciably exceed the Rayleigh line width in those
      liquids. The four-wave mixing method is applied both experimentally and
      theoretically to display the process as Rayleigh-induced parametric generation.
      We show that the amplification effect is provided predominantly by thermally
      induced coherent polarization oscillations, while an interference-assisted
      thermal grating provides formation of a self-induced optical cavity inside the
      interaction region.

PMID- 29601033
TI  - High-power, fixed, and tunable wavelength, grating-free cascaded Raman fiber
      lasers.
AB  - Cascaded Raman lasers enable high powers at various wavelength bands inaccessible
      with conventional rare-earth-doped lasers. The input and output wavelengths of
      conventional implementations are fixed by the constituent fiber gratings
      necessary for cascaded Raman conversion. We demonstrate here a simple
      architecture for high-power, fixed, and wavelength tunable, grating-free,
      cascaded Raman conversion between different wavelength bands. The architecture is
      based on the recently proposed distributed feedback Raman lasers. Here, we
      implement a module which converts the ytterbium band to the eye-safe 1.5 MUm
      region. We demonstrate pump-limited output powers of over 30 W in fixed and
      continuously wavelength tunable configurations.

PMID- 29601034
TI  - AlGaAs-based vertical-external-cavity surface-emitting laser exceeding 4  W of
      direct emission power in the 740-790  nm spectral range.
AB  - An optically pumped vertical-external-cavity surface-emitting laser (VECSEL) for
      direct emission in the 740-790 nm wavelength region is reported. The gain
      structure is based on 12 AlGaAs quantum wells. We demonstrate wavelength tuning
      between 747 nm and 788 nm and free-running operation with a maximum power of 4.24
      W (pump power limited) for a heat sink temperature of 14 degrees C. This laser
      system addresses a spectral gap not currently covered by VECSEL technology and
      represents the most powerful VECSEL reported within the 7XX-nm wavelength region.

PMID- 29601035
TI  - Simultaneous viscosity and elasticity measurement using laser speckle contrast
      imaging.
AB  - Viscosity and elasticity are closely related to the physiological characteristics
      of biological tissues. This Letter reports a simultaneous quantitative
      measurement of these parameters realized with the laser speckle contrast imaging
      method. The propagation of a Rayleigh wave induced by an acoustic speaker is
      traced, and the frequency-dependent velocity dispersion is extracted with the
      frequency-wavenumber spectrum analysis method. The viscosity and elasticity
      moduli of oil-in-gelatin tissue-mimicking phantoms are calculated by fitting the
      dispersion curves to the Voigt model. The method is validated by comparing it
      with the results obtained by using a conventional mechanical rheometer.

PMID- 29601036
TI  - Design and demonstration of ultra-high-Q silicon microring resonator based on a
      multi-mode ridge waveguide.
AB  - We present the design and experimental demonstration of the ultra-high-Q-factor
      silicon microring resonator based on a multi-mode ridge waveguide. The multi-mode
      ridge waveguide is designed to decrease the propagation loss and to improve the Q
      factor. The ultra-high Q factor of 1.1*106 is experimentally demonstrated, with
      the free spectrum range of 0.208 nm. The single-mode ridge waveguide is used in
      the coupling region to reduce the dimension of the microring resonator, and the
      bend radius is only 20 MUm. To precisely control the resonance wavelength, a
      small heater is implemented on the silicon microring resonator with the tuning
      efficiency of 7.1  pm/mW. The degenerate four-wave mixing of the silicon
      microring resonator is investigated, and the conversion efficiency is measured to
      be -15.5  dB without optimizing the dispersion of the microring resonator and
      carriers extraction.

PMID- 29601037
TI  - All-fiber radially/azimuthally polarized lasers based on mode coupling of tapered
      fibers.
AB  - We demonstrate a mode converter with an insertion loss of 0.36 dB based on mode
      coupling of tapered single-mode and two-mode fibers, and realize all-fiber
      flexible cylindrical vector lasers at 1550 nm. Attributing to the continuous
      distribution of a tangential electric field at taper boundaries, the laser is
      switchable between the radially and azimuthally polarized states by adjusting the
      input polarization. In the temporal domain, the operation is controllable among
      continuous-wave, Q-switched, and mode-locked statuses by changing the saturable
      absorber or pump strength. The duration of Q-switched radially/azimuthally
      polarized laser spans from 10.4/10.8 to 6/6.4 MUs at the pump range of 38 to 58
      mW, while that of the mode-locked pulse varies from 39.2/31.9 to 5.6/5.2 ps by
      controlling the laser bandwidth. The proposed laser combines the features of a
      cylindrical vector beam, a fiber laser, and an ultrafast pulse, providing a
      special and cost-effective source for practical applications.

PMID- 29601038
TI  - Terahertz adaptive optics with a deformable mirror.
AB  - We report on the wavefront correction of a terahertz (THz) beam using adaptive
      optics, which requires both a wavefront sensor that is able to sense the optical
      aberrations, as well as a wavefront corrector. The wavefront sensor relies on a
      direct 2D electro-optic imaging system composed of a ZnTe crystal and a CMOS
      camera. By measuring the phase variation of the THz electric field in the
      crystal, we were able to minimize the geometrical aberrations of the beam, thanks
      to the action of a deformable mirror. This phase control will open the route to
      THz adaptive optics in order to optimize the THz beam quality for both practical
      and fundamental applications.

PMID- 29601039
TI  - Optimized inhibited-coupling Kagome fibers at Yb-Nd:Yag (8.5  dB/km) and Ti:Sa
      (30 dB/km) ranges.
AB  - We report on the development of hypocycloid core-contour inhibited-coupling (IC)
      Kagome hollow-core photonic crystal fibers (HC-PCFs) with record transmission
      loss and spectral coverage that include the common industrial laser wavelengths.
      Using the scaling of the confinement loss with the core-contour negative
      curvature and the silica strut thickness, we fabricated an IC Kagome HC-PCF for
      Yb and Nd:Yag laser guidance with record loss level of 8.5 dB/km associated with
      a 225-nm-wide 3-dB bandwidth. A second HC-PCF is fabricated with reduced silica
      strut thickness while keeping the hypocycloid core contour. It exhibits a
      fundamental transmission window spanning down to the Ti:Sa spectral range and a
      loss figure of 30 dB/km at 750 nm. The fibers' modal properties and bending
      sensitivity show these HC-PCFs to be ideal for ultralow-loss, flexible, and
      robust laser beam delivery.

PMID- 29601040
TI  - Two-dimensional arbitrary nano-manipulation on a plasmonic metasurface.
AB  - In this Letter, we report on a plasmonic nano-ellipse metasurface with the
      purpose of trapping and two-dimensional (2D) arbitrary transport of nanoparticles
      by means of rotating the polarization of an excitation beam. The locations of hot
      spots within a metasurface are polarization dependent, thus making it possible to
      turn on/off the adjacent hot spots and then convey the trapped target by rotating
      the incident polarization state. For the case of a metasurface with a unit cell
      of perpendicularly orientated nano-ellipses, the hot spots with higher
      intensities are located at both apexes of the nano-ellipse whose major axis is
      parallel to the direction of polarization. When the polarization gradually
      rotates to its counterpart direction, the trapped particle may move around the
      ellipse and transfer to the most adjacent ellipse, due to the unbalanced trap
      potentials around the nano-ellipse. Clockwise and counterclockwise rotation would
      guide the particle in a different direction, which makes it possible to convey
      the particle arbitrarily within the plasmonic metasurface by setting a time
      sequence of polarization rotation. As confirmed by the three-dimensional finite
      difference time-domain analysis, our design offers a novel scheme of 2D arbitrary
      transport with nanometer accuracy, which could be used in many on-chip
      optofluidic applications.

PMID- 29601041
TI  - Line-scan spectrum-encoded imaging by dual-comb interferometry.
AB  - Herein, the method of spectrum-encoded dual-comb interferometry is introduced to
      measure a three-dimensional (3-D) profile with absolute distance information. By
      combining spectral encoding for wavelength-to-space mapping, dual-comb
      interferometry for decoding and optical reference for calibration, this system
      can obtain a 3-D profile of an object at a stand-off distance of 114 mm with a
      depth precision of 12 MUm. With the help of the reference arm, the absolute
      distance, reflectivity distribution, and depth information are simultaneously
      measured at a 5 kHz line-scan rate with free-running carrier-envelope offset
      frequencies. To verify the concept, experiments are conducted with multiple
      objects, including a resolution test chart, a three-stair structure, and a
      designed "ECNU" letter chain. The results show a horizontal resolution of ~22 
      MUm and a measurement range of 1.93 mm.

PMID- 29601042
TI  - MeV electron acceleration at 1  kHz with <10  mJ laser pulses: erratum.
AB  - In this erratum the funding section of Opt. Lett.42, 215 (2017)OPLEDP0146
      959210.1364/OL.42.000215 has been updated.

PMID- 29601043
TI  - All-fiber all-normal-dispersion femtosecond laser with a nonlinear multimodal
      interference-based saturable absorber.
AB  - In this Letter, we demonstrate, to the best of our knowledge, the first all-fiber
      all-normal-dispersion ytterbium-doped oscillator with a nonlinear multimodal
      interference-based saturable absorber capable of generating ultrashort
      dissipative soliton pulses. Additional to functioning as a saturable absorber,
      the use of multimode fiber segments between single-mode fibers also ensures the
      bandpass filtering via multimode interference reimaging necessary to obtain
      dissipative soliton mode locking. The oscillator generates dissipative soliton
      pulses at 1030 nm with 5.8 mW average power, 5 ps duration, and 44.25 MHz
      repetition rate. Pulses are dechirped to 276 fs via an external grating
      compressor. All-fiber cavity design ensures high stability, and ~70  dB sideband
      suppression is measured in the radio frequency spectrum. Numerical simulations
      are performed to investigate cavity dynamics, and obtained results are well
      matched with experimental observations. The proposed cavity presents an
      alternative approach to achieve all-fiber dissipative soliton mode locking with a
      simple and low-cost design.

PMID- 29601044
TI  - Ultracompact high-resolution photoacoustic microscopy.
AB  - Optical resolution photoacoustic microscopy (ORPAM), benefiting from rich optical
      contrast, scalable acoustic resolution, and deep penetration depth, is of great
      importance for the fields of biology and medicine. However, limited by the size
      and performance of reported optical/acoustic scanners, existing portable/handheld
      ORPAMs are bulky and heavy, and suffer from low imaging quality/speed. Here, we
      present an ultracompact ORPAM probe, which is miniature and light, and has high
      imaging quality. The probe only weighs 20 grams and has an outer size of 22 
      mm*30  mm*13  mm, a high lateral resolution of 3.8 MUm, and an effective imaging
      domain of 2  mm*2  mm. To show its advantages over existing ORPAMs, we apply this
      probe to image vasculatures of internal organs in a rat abdominal cavity and
      inspect the entire human oral cavity.

PMID- 29601045
TI  - Formulating the design of two freeform lens surfaces for point-like light
      sources.
AB  - Two freeform surfaces provide more degrees of freedom in designing illumination
      optics and can yield a better solution. The existing methods for point-like
      sources are mostly valid in designing one freeform surface. Designing two
      freeform surfaces for point-like sources still remains a challenging issue. In
      this Letter, we develop a general formulation of designing two freeform lens
      surfaces for point-like sources. The proposed method is very robust in designing
      freeform lenses with two elaborately designed surfaces. The examples clearly show
      that using two freeform surfaces yields better solutions to challenging
      illumination problems with ultra-high energy efficiency.

PMID- 29601046
TI  - Observation of subfemtosecond fluctuations of the pulse separation in a soliton
      molecule.
AB  - In this work, we study the timing instability of a scalar twin-pulse soliton
      molecule generated by a passively mode-locked Er-fiber laser. Subfemtosecond
      precision relative timing jitter characterization between the two solitons
      composing the molecule is enabled by the balanced optical cross-correlation (BOC)
      method. Jitter spectral density reveals a short-term (on the microsecond to
      millisecond timescale) random fluctuation of the pulse separation even in the
      robust stationary soliton molecules. The root-mean-square (rms) timing jitter is
      on the order of femtoseconds depending on the pulse separation and the mode
      locking regime. The lowest rms timing jitter is 0.83 fs, which is observed in the
      dispersion managed mode-locking regime. Moreover, the BOC method has proved to be
      capable of resolving the soliton interaction dynamics in various vibrating
      soliton molecules.

PMID- 29601047
TI  - Estimating Dynamic Signals From Trial Data With Censored Values.
AB  - Censored data occur commonly in trial-structured behavioral experiments and many
      other forms of longitudinal data. They can lead to severe bias and reduction of
      statistical power in subsequent analyses. Principled approaches for dealing with
      censored data, such as data imputation and methods based on the complete data's
      likelihood, work well for estimating fixed features of statistical models but
      have not been extended to dynamic measures, such as serial estimates of an
      underlying latent variable over time. Here we propose an approach to the censored
      data problem for dynamic behavioral signals. We developed a state-space modeling
      framework with a censored observation process at the trial timescale. We then
      developed a filter algorithm to compute the posterior distribution of the state
      process using the available data. We showed that special cases of this framework
      can incorporate the three most common approaches to censored observations:
      ignoring trials with censored data, imputing the censored data values, or using
      the full information available in the data likelihood. Finally, we derived a
      computationally efficient approximate Gaussian filter that is similar in
      structure to a Kalman filter, but that efficiently accounts for censored data. We
      compared the performances of these methods in a simulation study and provide
      recommendations of approaches to use, based on the expected amount of censored
      data in an experiment. These new techniques can broadly be applied in many
      research domains in which censored data interfere with estimation, including
      survival analysis and other clinical trial applications.

PMID- 29601048
TI  - Consensus clustering approach to group brain connectivity matrices.
AB  - A novel approach rooted on the notion of consensus clustering, a strategy
      developed for community detection in complex networks, is proposed to cope with
      the heterogeneity that characterizes connectivity matrices in health and disease.
      The method can be summarized as follows: (a) define, for each node, a distance
      matrix for the set of subjects by comparing the connectivity pattern of that node
      in all pairs of subjects; (b) cluster the distance matrix for each node; (c)
      build the consensus network from the corresponding partitions; and (d) extract
      groups of subjects by finding the communities of the consensus network thus
      obtained. Different from the previous implementations of consensus clustering, we
      thus propose to use the consensus strategy to combine the information arising
      from the connectivity patterns of each node. The proposed approach may be seen
      either as an exploratory technique or as an unsupervised pretraining step to help
      the subsequent construction of a supervised classifier. Applications on a toy
      model and two real datasets show the effectiveness of the proposed methodology,
      which represents heterogeneity of a set of subjects in terms of a weighted
      network, the consensus matrix.

PMID- 29601050
TI  - Editorial.

PMID- 29601049
TI  - Cognitive genomics: Linking genes to behavior in the human brain.
AB  - Correlations of genetic variation in DNA with functional brain activity have
      already provided a starting point for delving into human cognitive mechanisms.
      However, these analyses do not provide the specific genes driving the
      associations, which are complicated by intergenic localization as well as tissue
      specific epigenetics and expression. The use of brain-derived expression datasets
      could build upon the foundation of these initial genetic insights and yield genes
      and molecular pathways for testing new hypotheses regarding the molecular bases
      of human brain development, cognition, and disease. Thus, coupling these human
      brain gene expression data with measurements of brain activity may provide genes
      with critical roles in brain function. However, these brain gene expression
      datasets have their own set of caveats, most notably a reliance on postmortem
      tissue. In this perspective, I summarize and examine the progress that has been
      made in this realm to date, and discuss the various frontiers remaining, such as
      the inclusion of cell-type-specific information, additional physiological
      measurements, and genomic data from patient cohorts.

PMID- 29601051
TI  - The future of network neuroscience.
AB  - Understanding the brain represents one of the most profound and pressing
      scientific challenges of the 21st century. As brain data have increased in volume
      and complexity, the tools and methods of network science have become
      indispensable for mapping and modeling brain structure and function, for bridging
      scales of organization, and for integrating across empirical and computational
      methodologies. The creation of a new journal, Network Neuroscience, will
      contribute to guiding this emerging and interdisciplinary field in new
      directions.

PMID- 29601052
TI  - The role of neoadjuvant chemoradiotherapy in multimodality treatment of
      esophageal or gastroesophageal junction cancer.

PMID- 29601054
TI  - Corrigendum to "The Effect of Arch Height and Material Hardness of Personalized
      Insole on Correction and Tissues of Flatfoot".
AB  - [This corrects the article DOI: 10.1155/2017/8614341.].

PMID- 29601053
TI  - Implications of Information Theory for Computational Modeling of Schizophrenia.
AB  - Information theory provides a formal framework within which information
      processing and its disorders can be described. However, information theory has
      rarely been applied to modeling aspects of the cognitive neuroscience of
      schizophrenia. The goal of this article is to highlight the benefits of an
      approach based on information theory, including its recent extensions, for
      understanding several disrupted neural goal functions as well as related
      cognitive and symptomatic phenomena in schizophrenia. We begin by demonstrating
      that foundational concepts from information theory-such as Shannon information,
      entropy, data compression, block coding, and strategies to increase the signal-to
      noise ratio-can be used to provide novel understandings of cognitive impairments
      in schizophrenia and metrics to evaluate their integrity. We then describe more
      recent developments in information theory, including the concepts of infomax,
      coherent infomax, and coding with synergy, to demonstrate how these can be used
      to develop computational models of schizophrenia-related failures in the tuning
      of sensory neurons, gain control, perceptual organization, thought organization,
      selective attention, context processing, predictive coding, and cognitive
      control. Throughout, we demonstrate how disordered mechanisms may explain both
      perceptual/cognitive changes and symptom emergence in schizophrenia. Finally, we
      demonstrate that there is consistency between some information-theoretic concepts
      and recent discoveries in neurobiology, especially involving the existence of
      distinct sites for the accumulation of driving input and contextual information
      prior to their interaction. This convergence can be used to guide future theory,
      experiment, and treatment development.

PMID- 29601055
TI  - Correction: Assessing tumor molecular profiling to guide treatments for patients
      with advanced female genital tract malignancy.
AB  - [This corrects the article DOI: 10.18632/oncotarget.23675.].

PMID- 29601056
TI  - Screening for disruptive behaviour problems in preschool children in primary
      health care settings.
AB  - Disruptive behaviour problems in preschool children are significant risk factors
      for, and potential components of, neurodevelopmental and mental health disorders.
      Some noncompliance, temper tantrums and aggression between 2 and 5 years of age
      are normal and transient. However, problematic levels of disruptive behaviour,
      specifically when accompanied by functional impairment and/or significant
      distress, should be identified because early intervention can improve outcome
      trajectories. This position statement provides an approach to early
      identification using clinical screening at periodic health examinations, followed
      by a systematic mental health examination that includes standardized measures.
      The practitioner should consider a range of environmental, developmental, family
      and parent-child relationship factors to evaluate the clinical significance of
      disruptive behaviours. Options within a management plan include regular
      monitoring, accompanied by health guidance and parenting advice, referral to
      parent behaviour training as a core evidence-based intervention, and referral to
      specialty care for preschool children with significant disruptive behaviours,
      developmental or mental health comorbidities, or who are not responding to first
      line interventions.

PMID- 29601057
TI  - CORRIGENDUM FOR "F2-Isoprostanes Reflect Oxidative Stress Correlated With Lean
      Mass and Bone Density but Not Insulin Resistance".
AB  - [This corrects the article DOI: 10.1210/js.2017-00006.][This corrects the article
      DOI: 10.1210/js.2017-00006.].

PMID- 29601058
TI  - Hybrid procedures for persistent atrial fibrillation: necessity and timing of the
      catheter ablation stage.

PMID- 29601059
TI  - Feeding route or learning route for nutrition in critically ill.

PMID- 29601060
TI  - Revealing Neurocomputational Mechanisms of Reinforcement Learning and Decision
      Making With the hBayesDM Package.
AB  - Reinforcement learning and decision-making (RLDM) provide a quantitative
      framework and computational theories with which we can disentangle psychiatric
      conditions into the basic dimensions of neurocognitive functioning. RLDM offer a
      novel approach to assessing and potentially diagnosing psychiatric patients, and
      there is growing enthusiasm for both RLDM and computational psychiatry among
      clinical researchers. Such a framework can also provide insights into the brain
      substrates of particular RLDM processes, as exemplified by model-based analysis
      of data from functional magnetic resonance imaging (fMRI) or
      electroencephalography (EEG). However, researchers often find the approach too
      technical and have difficulty adopting it for their research. Thus, a critical
      need remains to develop a user-friendly tool for the wide dissemination of
      computational psychiatric methods. We introduce an R package called hBayesDM
      (hierarchical Bayesian modeling of Decision-Making tasks), which offers
      computational modeling of an array of RLDM tasks and social exchange games. The
      hBayesDM package offers state-of-the-art hierarchical Bayesian modeling, in which
      both individual and group parameters (i.e., posterior distributions) are
      estimated simultaneously in a mutually constraining fashion. At the same time,
      the package is extremely user-friendly: users can perform computational modeling,
      output visualization, and Bayesian model comparisons, each with a single line of
      coding. Users can also extract the trial-by-trial latent variables (e.g.,
      prediction errors) required for model-based fMRI/EEG. With the hBayesDM package,
      we anticipate that anyone with minimal knowledge of programming can take
      advantage of cutting-edge computational-modeling approaches to investigate the
      underlying processes of and interactions between multiple decision-making (e.g.,
      goal-directed, habitual, and Pavlovian) systems. In this way, we expect that the
      hBayesDM package will contribute to the dissemination of advanced modeling
      approaches and enable a wide range of researchers to easily perform computational
      psychiatric research within different populations.

PMID- 29601061
TI  - Revascularizing coronary artery disease in patients undergoing transcatheter
      aortic valve implantation.

PMID- 29601062
TI  - Transportation of horses to Japan for slaughter - A comment.

PMID- 29601063
TI  - Correction: Photobleaching of YOYO-1 in super-resolution single DNA fluorescence
      imaging.
AB  - [This corrects the article DOI: 10.3762/bjnano.8.229.].

PMID- 29601064
TI  - Screen time and young children: Promoting health and development in a digital
      world.
AB  - The digital landscape is evolving more quickly than research on the effects of
      screen media on the development, learning and family life of young children. This
      statement examines the potential benefits and risks of screen media in children
      younger than 5 years, focusing on developmental, psychosocial and physical
      health. Evidence-based guidance to optimize and support children's early media
      experiences involves four principles: minimizing, mitigating, mindfully using and
      modelling healthy use of screens. Knowing how young children learn and develop
      informs best practice strategies for health care providers.

PMID- 29601065
TI  - DeepScope: Nonintrusive Whole Slide Saliency Annotation and Prediction from
      Pathologists at the Microscope.
AB  - Modern digital pathology departments have grown to produce whole-slide image data
      at petabyte scale, an unprecedented treasure chest for medical machine learning
      tasks. Unfortunately, most digital slides are not annotated at the image level,
      hindering large-scale application of supervised learning. Manual labeling is
      prohibitive, requiring pathologists with decades of training and outstanding
      clinical service responsibilities. This problem is further aggravated by the
      United States Food and Drug Administration's ruling that primary diagnosis must
      come from a glass slide rather than a digital image. We present the first end-to
      end framework to overcome this problem, gathering annotations in a nonintrusive
      manner during a pathologist's routine clinical work: (i) microscope-specific 3D
      printed commodity camera mounts are used to video record the glass-slide-based
      clinical diagnosis process; (ii) after routine scanning of the whole slide, the
      video frames are registered to the digital slide; (iii) motion and observation
      time are estimated to generate a spatial and temporal saliency map of the whole
      slide. Demonstrating the utility of these annotations, we train a convolutional
      neural network that detects diagnosis-relevant salient regions, then report
      accuracy of 85.15% in bladder and 91.40% in prostate, with 75.00% accuracy when
      training on prostate but predicting in bladder, despite different pathologists
      examining the different tissues. When training on one patient but testing on
      another, AUROC in bladder is 0.79+/-0.11 and in prostate is 0.96+/-0.04. Our tool
      is available at https://bitbucket.org/aschaumberg/deepscope.

PMID- 29601066
TI  - Nonrandom network connectivity comes in pairs.
AB  - Overrepresentation of bidirectional connections in local cortical networks has
      been repeatedly reported and is a focus of the ongoing discussion of nonrandom
      connectivity. Here we show in a brief mathematical analysis that in a network in
      which connection probabilities are symmetric in pairs, Pij = Pji , the
      occurrences of bidirectional connections and nonrandom structures are inherently
      linked; an overabundance of reciprocally connected pairs emerges necessarily when
      some pairs of neurons are more likely to be connected than others. Our numerical
      results imply that such overrepresentation can also be sustained when connection
      probabilities are only approximately symmetric.

PMID- 29601067
TI  - Veterinary School Admission - A comment.

PMID- 29601068
TI  - Possible refinement of the standard treatment of esophageal cancer.

PMID- 29601069
TI  - Correction: The benefit of tumor molecular profiling on predicting treatments for
      colorectal adenocarcinomas.
AB  - [This corrects the article DOI: 10.18632/oncotarget.24257.].

PMID- 29601070
TI  - Correction: Does molecular profiling of tumors using the Caris molecular
      intelligence platform improve outcomes for cancer patients?
AB  - [This corrects the article DOI: 10.18632/oncotarget.24258.].

PMID- 29601071
TI  - Erratum: Detection of Replication Competent Lentivirus Using a qPCR Assay for VSV
      G.
AB  - [This corrects the article DOI: 10.1016/j.omtm.2017.09.001.].

PMID- 29601072
TI  - Correction: Librarians against scientists: Oncotarget's lesson.
AB  - [This corrects the article DOI: 10.18632/oncotarget.24272.].

PMID- 29601073
TI  - Do Ayurveda drugs induce liver injury?
AB  - Drugs fulfilling the criterion of a standard drug will always become panacea
      provided, if they are used properly. On the other hand, a poorly manufactured
      drug however used skillfully, will prove to be a poison. Texts of Ayurveda, do
      mention hazards of drugs, which are not properly manufactured or administered.
      Art of drug administration is unique in this ancient medical science that
      cautions towards concentrating on dose, indications, contra-indications, suitable
      vehicle, specific diet, certain restrictions etc., while administering medicines
      in suitable individuals. Though a huge amount of information is available and
      evidences are being generated on the usefulness of traditional practices in
      global healthcare; there is a need of generating awareness on Promoting rational
      use of traditional medicines in particular to Ayurvedic drugs. Conventional
      researchers wish to work on traditional formulations have to understand
      traditional principles and involve traditional physicians in their researches in
      the benefit of mankind.

PMID- 29601074
TI  - Assessing Progression of Resident Proficiency during Ophthalmology Residency
      Training: Utility of Serial Clinical Skill Evaluations.
AB  - Objective: The Accreditation Council for Graduate Medical Education (ACGME) has
      mandated that residency programs document progression of competency-based
      outcomes. The Ophthalmic Clinical Evaluation Exercise (OCEX) assesses clinical
      skills in ophthalmology residents during patient encounters. Although OCEX has
      been validated for assessing several of the ACGME-mandated competencies, it was
      unclear whether OCEX can measure the development of proficiency during residency.
      This study evaluated whether OCEX can discriminate skill levels across years in
      training. Methods: In 2017, the authors performed a retrospective analysis on
      modified OCEX evaluations collected for 22 residents over 3 years at 2 residency
      programs. OCEX subcomponent scores were averaged to generate a mean score for
      each evaluation, followed by linear regression analysis for mean scores over time
      for individual residents. One-way ANOVA with repeated measures was used to
      compare scores aggregated over an academic year between resident classes. The
      authors also surveyed internal faculty evaluators and nationwide ophthalmology
      residency program directors on their use of OCEX. Results: Mean OCEX scores for
      individual residents and resident class averages showed variable trajectories
      over the course of residency. There was no consistent effect of increasing level
      of training on scores. Surveys of evaluators and program directors indicated
      different interpretations of the grading scale anchors and irregular
      participation by faculty. Conclusion: This dataset suggests that, despite clear
      behavioral anchors and faculty development on the use of the tool, evaluators
      still apply inconsistent grading standards that limit the OCEX from accurately
      monitoring longitudinal development of resident clinical performance in real
      world practice.

PMID- 29601075
TI  - The Night That Was Not Still.

PMID- 29601076
TI  - Syncope, Hypotension, and Falls in the Treatment of Hypertension: Results from
      the Randomized Clinical Systolic Blood Pressure Intervention Trial.
AB  - OBJECTIVE: To determine predictors of serious adverse events (SAEs) involving
      syncope, hypotension, and falls, with particular attention to age, in the
      Systolic Blood Pressure Intervention Trial. DESIGN: Randomized clinical trial.
      SETTING: Academic and private practices across the United States (N = 102).
      PARTICIPANTS: Adults aged 50 and older with a systolic blood pressure (SBP) of
      130 to 180 mmHg at high risk of cardiovascular disease events, but without
      diabetes, history of stroke, symptomatic heart failure or ejection fraction less
      than 35%, dementia, or standing SBP less than 110 mmHg (N = 9,361). INTERVENTION:
      Treatment of SBP to a goal of less than 120 mmHg or 140 mmHg. MEASUREMENTS:
      Outcomes were SAEs involving syncope, hypotension, and falls. Predictors were
      treatment assignment, demographic characteristics, comorbidities, baseline
      measurements, and baseline use of cardiovascular medications. RESULTS: One
      hundred seventy-two (1.8%) participants had SAEs involving syncope, 155 (1.6%)
      hypotension, and 203 (2.2%) falls. Randomization to intensive SBP control was
      associated with greater risk of an SAE involving hypotension (hazard ratio (HR) =
      1.67, 95% confidence interval (CI) = 1.21-2.32, P = .002), and possibly syncope
      (HR = 1.32, 95% CI = 0.98-1.79, P = .07), but not falls (HR = 0.98, 95% CI = 0.75
      1.29, P = .90). Risk of all three outcomes was higher for participants with
      chronic kidney disease or frailty. Older age was also associated with greater
      risk of syncope, hypotension, and falls, but there was no age-by-treatment
      interaction for any of the SAE outcomes. CONCLUSIONS: Participants randomized to
      intensive SBP control had greater risk of hypotension and possibly syncope, but
      not falls. The greater risk of developing these events associated with intensive
      treatment did not vary according to age.

PMID- 29601078
TI  - Hypertension in Older Adults in the Wake of the Systolic Blood Pressure
      Intervention Trial.

PMID- 29601077
TI  - Investigation of factors influencing the immunogenicity of hCG as a potential
      cancer vaccine.
AB  - Human chorionic gonadotrophin (hCG) and its beta-subunit (hCGbeta) are tumour
      autocrine growth factors whose presence in the serum of cancer patients has been
      linked to poorer prognosis. Previous studies have shown that vaccines which
      target these molecules and/or the 37 amino acid C-terminal hCGbeta peptide
      (hCGbetaCTP) induce antibody responses in a majority of human recipients. Here we
      explored whether the immunogenicity of vaccines containing an hCGbeta mutant
      (hCGbetaR68E, designed to eliminate cross-reactivity with luteinizing hormone) or
      hCGbetaCTP could be enhanced by coupling the immunogen to different carriers
      [keyhole limpet haemocyanin (KLH) or heat shock protein 70 (Hsp70)] using
      different cross-linkers [1-ethyl-3(3-dimethylaminopropyl)carboiimide (EDC) or
      glutaraldehyde (GAD)] and formulated with different adjuvants (RIBI or Montanide
      ISA720). While there was little to choose between KLH and Hsp70 as carriers,
      their influence on the effectiveness of a vaccine containing the BAChCGbetaR68E
      mutant was less marked, presumably because, being a foreign species, this mutant
      protein itself might provide T helper epitopes. The mutant provided a
      significantly better vaccine than the hCGbetaCTP peptide irrespective of the
      carrier used, how it was cross-linked to the carrier or which adjuvant was used
      when hCG was the target. Nonetheless, for use in humans where hCG is a tolerated
      self-protein, the need for a carrier is of fundamental importance. Highest
      antibody titres were obtained by linking the BAChCGbetaR68E to Hsp70 as a carrier
      by GAD and using RIBI as the adjuvant, which also resulted in antibodies with
      significantly higher affinity than those elicited by hCGbetaCTP peptide vaccine.
      This makes this mutant vaccine a promising candidate for therapeutic studies in
      hCGbeta-positive cancer patients.

PMID- 29601079
TI  - Relationship between intraoperative non-technical performance and technical
      events in bariatric surgery.
AB  - BACKGROUND: The operating theatre is a unique environment with complex team
      interactions, where technical and non-technical performance affect patient
      outcomes. The correlation between technical and non-technical performance,
      however, remains underinvestigated. The purpose of this study was to explore
      these interactions in the operating theatre. METHODS: A prospective single-centre
      observational study was conducted at a tertiary academic medical centre. One
      surgeon and three fellows participated as main operators. All patients who
      underwent a laparoscopic Roux-en-Y gastric bypass and had the procedures captured
      using the Operating Room Black Box(r) platform were included. Technical
      assessment was performed using the Objective Structured Assessment of Technical
      Skills and Generic Error Rating Tool instruments. For non-technical assessment,
      the Non-Technical Skills for Surgeons (NOTSS) and Scrub Practitioners' List of
      Intraoperative Non-Technical Skills (SPLINTS) tools were used. Spearman rank
      order correlation and N-gram statistics were conducted. RESULTS: Fifty-six
      patients were included in the study and 90 procedural steps (gastrojejunostomy
      and jejunojejunostomy) were analysed. There was a moderate to strong correlation
      between technical adverse events (rs  = 0.417-0.687), rectifications (rs  = 0.380
      0.768) and non-technical performance of the surgical and nursing teams (NOTSS and
      SPLINTS). N-gram statistics showed that after technical errors, events and prior
      rectifications, the staff surgeon and the scrub nurse exhibited the most positive
      non-technical behaviours, irrespective of operator (staff surgeon or fellow).
      CONCLUSION: This study demonstrated that technical and non-technical performances
      are related, on both an individual and a team level. Valuable data can be
      obtained around intraoperative errors, events and rectifications.

PMID- 29601080
TI  - Comparison of smartphone addiction and loneliness in high school and university
      students.
AB  - PURPOSE: This study was conducted to compare the relationship between the
      smartphone addiction and loneliness in high school and university students.
      DESIGN AND METHODS: A correlation and descriptive study from a convenience sample
      of 1156 high school and university students. Questionnaire, Smartphone Addiction
      scale, and Short Loneliness scale were used to collect the data of the study.
      FINDINGS: No relationship was found between the smartphone addiction and
      loneliness in high school and university students. PRACTICE IMPLACITIONS: It is
      recommended to organize comprehensive training programs for the students and
      their families in the school health services.

PMID- 29601081
TI  - Outcome of open abdominal management following military trauma.
AB  - BACKGROUND: Temporary abdominal closure (TAC) is increasingly common after
      military and civilian major trauma. Primary fascial closure cannot be achieved
      after TAC in 30 per cent of civilian patients; subsequent abdominal wall
      reconstruction carries significant morbidity. This retrospective review aimed to
      determine this morbidity in a UK military cohort. METHODS: A prospectively
      maintained database of all injured personnel from the Iraq and Afghanistan
      conflicts was searched from 1 January 2003 to 31 December 2014 for all patients
      who had undergone laparotomy in a deployed military medical treatment facility.
      This database, the patients' hospital notes and their primary care records were
      searched. RESULTS: Laparotomy was performed in a total of 155 patients who
      survived to be repatriated to the UK; records were available for 150 of these
      patients. Seventy-seven patients (51.3 per cent) had fascial closure at first
      laparotomy, and 73 (48.7 per cent) had a period of TAC. Of the 73 who had TAC,
      two died before closure and two had significant abdominal wall loss from blast
      injury and were excluded from analysis. Of the 69 remaining patients, 65 (94 per
      cent) were able to undergo delayed primary fascial closure. The median duration
      of follow-up from injury was 1257 (range 1-4677) days for the whole cohort. Nine
      (12 per cent) of the 73 patients who underwent TAC subsequently developed an
      incisional hernia, compared with ten (13 per cent) of the 77 patients whose
      abdomen was closed at the primary laparotomy (P = 1.000). CONCLUSION: Rates of
      delayed primary closure of abdominal fascia after temporary abdominal closure
      appear high. Subsequent rates of incisional hernia formation were similar in
      patients undergoing delayed primary closure and those who had closure at the
      primary laparotomy.

PMID- 29601082
TI  - Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients
      with oesophagogastric cancer.
AB  - BACKGROUND: Neoadjuvant chemotherapy may have a detrimental impact on
      cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic
      threshold by cardiopulmonary exercise testing (CPET) provides an objective
      measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict
      perioperative risk. A low anaerobic threshold is associated with increased
      morbidity after oesophagogastrectomy. The aim of this study was to establish
      whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether
      there is recovery of fitness before surgery for oesophageal and gastric
      adenocarcinoma. METHODS: CPET was completed before, immediately after (week 0),
      and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic
      threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible
      measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were
      compared before and after neoadjuvant chemotherapy, and at the three time
      intervals. RESULTS: Some 31 patients were recruited. The mean anaerobic threshold
      was lower following neoadjuvant treatment: 15.3 ml per kg per min before
      chemotherapy versus 11.8, 12.1 and 12.6 ml per kg per min at week 0, 2 and 4
      respectively (P < 0.010). Measurements were also significantly different at each
      time point (P < 0.010). The same pattern was noted for Vo2 peak between values
      before chemotherapy (21.7 ml per kg per min) and at weeks 0, 2 and 4 (17.5, 18.6
      and 19.3 ml per kg per min respectively) (P < 0.010). The reduction in anaerobic
      threshold and Vo2 peak did not improve during the time between completion of
      neoadjuvant chemotherapy and surgery. CONCLUSION: There was a decrease in
      cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was
      sustained up to the point of surgery at 4 weeks after chemotherapy.

PMID- 29601083
TI  - Analysis of Episodes of Care in Medicare Beneficiaries Newly Diagnosed with
      Alzheimer's Disease.
AB  - OBJECTIVES: To study transitions between healthcare settings and quantify the
      cost burdens associated with different combinations of transitions during a 6
      month period before initial Alzheimer's disease (AD) diagnosis so as to
      investigate how using an episode-of-care approach to payment for specific disease
      states might apply in AD. DESIGN: A retrospective observational cohort study.
      SETTING: United States. PARTICIPANTS: A random sample of 8,995 individuals aged
      65 to 100 with a diagnosis of AD (International Classification of Diseases, Ninth
      Revision, Clinical Modification code 331.0) were identified from the Medicare
      database between January 1, 2011, and June 30, 2014. This analysis identified
      individuals with AD diagnosed in inpatient (18%), skilled nursing facility (SNF)
      (1%), hospice (4%), and home and outpatient (77%) settings and analyzed episodes
      that began in the index setting (defined as the care setting in which the
      individual was first diagnosed with AD). MEASUREMENTS: Study outcomes included
      number of transitions between settings, primary discharge diagnoses, and total
      all-cause healthcare costs during the 6 months after the AD diagnosis. RESULTS:
      The average numbers of transitions between care settings were 2.8 originating
      from an inpatient setting, 2.4 from a SNF, 0.3 from a hospice setting and 0.7
      from a home or outpatient setting during 6 months post-AD diagnosis. The overall
      cost burden during the 6 months after AD diagnosis (including costs incurred at
      the index setting) was high for individuals diagnosed in a nonambulatory setting
      (mean $41,468). Individuals diagnosed in an ambulatory setting incurred only
      $12,597 in costs during the same period. CONCLUSION: Episodes of care can be
      defined and studied in individuals with AD. An episode-of-care approach to
      payment could encourage providers to use the continuum of care needed for quality
      medical management in AD more efficiently.

PMID- 29601085
TI  - The Gift.

PMID- 29601084
TI  - Elder Abuse and Chronic Pain: Cross-Sectional and Longitudinal Results from the
      Preventing Elder Abuse and Neglect Initiative.
AB  - OBJECTIVES: To examine the cross-sectional and longitudinal relationships between
      elder abuse and neglect (EAN) and chronic pain in rural older Malaysians. DESIGN:
      Two-year prospective cohort study. SETTING: Kuala Pilah, a district in Negeri
      Sembilan approximately 100 km from the capital city, Kuala Lumpur. PARTICIPANTS:
      Community-dwelling older adults aged 60 and older. Using a multistage cluster
      sampling strategy, 1,927 respondents were recruited and assessed at baseline, of
      whom 1,189 were re-assessed 2 years later. MEASURES: EAN was determined using the
      modified Conflict Tactic Scale, and chronic pain was assessed through self-report
      using validated questions. RESULTS: The prevalence of chronic pain was 20.4%.
      Cross-sectional results revealed 8 variables significantly associated with
      chronic pain-age, education, income, comorbidities, self-rated health,
      depression, gait speed, and EAN. Abused elderly adults were 1.52 times as likely
      to have chronic pain (odds ratio=1.52, 95% confidence interval (CI)=1.03-2.27),
      although longitudinal analyses showed no relationship between EAN and risk of
      chronic pain (risk ratio=1.14, 95% CI=0.81-1.60). This lack of causal link was
      consistent when comparing analysis with complete cases with that of imputed data.
      CONCLUSION: Our findings indicate no temporal relationship between EAN and
      chronic pain but indicated cross-sectional associations between the two. This
      might indicate that, although EAN does not lead to chronic pain, individuals with
      greater physical limitations are more vulnerable to abuse. Our study also shows
      the importance of cohort design in determining causal relationships between EAN
      and potentially linked health outcomes.

PMID- 29601086
TI  - SCN1A variants associated with sudden infant death syndrome.
AB  - We identified SCN1A variants in 2 infants who died of sudden infant death
      syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of
      10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the
      other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously
      associated with epilepsy. Functional evaluation in a heterologous expression
      system demonstrated partial loss of function for both G682V and the compound
      variant L1296M/E1308D. Our cases represent a novel association between SCN1A and
      SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide
      insights into SIDS and support genetic evaluation focused on epilepsy genes in
      SIDS.

PMID- 29601087
TI  - Construct and criterion validity testing of the Non-Technical Skills for Surgeons
      (NOTSS) behaviour assessment tool using videos of simulated operations.
AB  - BACKGROUND: Surgeons' non-technical skills are an important part of surgical
      performance and surgical education. The most widely adopted assessment tool is
      the Non-Technical Skills for Surgeons (NOTSS) behaviour rating system.
      Psychometric analysis of this tool to date has focused on inter-rater reliability
      and feasibility rather than validation. METHODS: NOTSS assessments were collected
      from two groups of consultant/attending surgeons in the UK and USA, who rated
      behaviours of the lead surgeon during a video-based simulated crisis scenario
      after either online or classroom instruction. The process of validation consisted
      of assessing construct validity, scale reliability and concurrent criterion
      validity, and undertaking a sensitivity analysis. Central to this was
      confirmatory factor analysis to evaluate the structure of the NOTSS taxonomy.
      RESULTS: Some 255 consultant surgeons participated in the study. The four
      category NOTSS model was found to have robust construct validity evidence, and a
      superior fit compared with alternative models. Logistic regression and
      sensitivity analysis revealed that, after adjusting for technical skills, for
      every 1-point increase in NOTSS score of the lead surgeon, the odds of having a
      higher versus lower patient safety score was 2.29 times. The same pattern of
      results was obtained for a broad mix of surgical specialties (UK) as well as a
      single discipline (cardiothoracic, USA). CONCLUSION: The NOTSS tool can be
      applied in research and education settings to measure non-technical skills in a
      valid and efficient manner.

PMID- 29601089
TI  - Reply.

PMID- 29601088
TI  - Blocking H1/H2 histamine receptors inhibits damage/fibrosis in Mdr2-/- mice and
      human cholangiocarcinoma tumorigenesis.
AB  - : Primary sclerosing cholangitis (PSC) patients are at risk of developing
      cholangiocarcinoma (CCA). We have shown that (1) histamine increases biliary
      hyperplasia through H1/H2 histamine receptors (HRs) and (2) histamine levels
      increase and mast cells (MCs) infiltrate during PSC and CCA. We examined the
      effects of chronic treatment with H1/H2HR antagonists on PSC and CCA. Wild-type
      and multidrug-resistant knockout (Mdr2-/- ) mice were treated by osmotic
      minipumps with saline, mepyramine, or ranitidine (10 mg/kg body weight/day) or a
      combination of mepyramine/ranitidine for 4 weeks. Liver damage was assessed by
      hematoxylin and eosin. We evaluated (1) H1/H2HR expression, (2) MC presence, (3)
      L-histidine decarboxylase/histamine axis, (4) cholangiocyte proliferation/bile
      duct mass, and (5) fibrosis/hepatic stellate cell activation. Nu/nu mice were
      implanted with Mz-ChA-1 cells into the hind flanks and treated with saline,
      mepyramine, or ranitidine. Tumor growth was measured, and (1) H1/H2HR expression,
      (2) proliferation, (3) MC activation, (4) angiogenesis, and (5) epithelial
      mesenchymal transition (EMT) were evaluated. In vitro, human hepatic stellate
      cells were evaluated for H1HR and H2HR expression. Cultured cholangiocytes and
      CCA lines were treated with saline, mepyramine, or ranitidine (25 MUM) before
      evaluating proliferation, angiogenesis, EMT, and potential signaling mechanisms.
      H1/H2HR and MC presence increased in human PSC and CCA. In H1/H2HR antagonist
      (alone or in combination)-treated Mdr2-/- mice, liver and biliary damage and
      fibrosis decreased compared to saline treatment. H1/H2HR antagonists decreased
      tumor growth, serum histamine, angiogenesis, and EMT. In vitro, H1/H2HR blockers
      reduced biliary proliferation, and CCA cells had decreased proliferation,
      angiogenesis, EMT, and migration. CONCLUSION: Inhibition of H1/H2HR reverses PSC
      associated damage and decreases CCA growth, angiogenesis, and EMT; because PSC
      patients are at risk of developing CCA, using HR blockers may be therapeutic for
      these diseases. (Hepatology 2018).

PMID- 29601090
TI  - Nonalcoholic fatty liver disease: Is it time for combination treatment and a
      diabetes-like approach?

PMID- 29601091
TI  - "To screen or not to screen": Comparing the health and economic benefits of early
      peanut introduction strategies in five countries.
AB  - BACKGROUND: Early peanut introduction (EPI) in the first year of life is
      associated with reduced risk of developing peanut allergy in children with either
      severe eczema and/or egg allergy. However, EPI recommendations differ among
      countries with formal guidelines. METHODS: Using simulation and Markov modeling
      over a 20-year horizon to attempt to explore optimal EPI strategies applied to
      the US population, we compared high-risk infant-specific IgE peanut screening
      (US/Canadian) with the Australiasian Society for Clinical Immunology and Allergy
      (Australia/New Zealand) (ASCIA) and the United Kingdom Department of Health
      (UKDOH)-published EPI approaches. RESULTS: Screening peanut skin testing of all
      children with early-onset eczema and/or egg allergy before in-office peanut
      introduction was dominated by a no screening approach, in terms of number of
      cases of peanut allergy prevented, quality-adjusted life years (QALY), and
      healthcare costs, although screening resulted in a slightly lower rate of
      allergic reactions to peanut per patient in high-risk children. Considering costs
      of peanut allergy in high-risk children, the per-patient cost of early
      introduction without screening over the model horizon was $6556.69 (95%CI,
      $6512.76-$6600.62), compared with a cost of $7576.32 (95%CI, $7531.38-$7621.26)
      for skin test screening prior to introduction. From a US societal perspective,
      screening prior to introduction cost $654 115 322 and resulted in 3208 additional
      peanut allergy diagnoses. Both screening and nonscreening approaches dominated
      deliberately delayed peanut introduction. CONCLUSIONS: A no-screening approach
      for EPI has superior health and economic benefits in terms of number of peanut
      allergy cases prevented, QALY, and total healthcare costs compared to screening
      and in-office peanut introduction.

PMID- 29601092
TI  - Different visual development: norms for visual acuity in children with Down's
      syndrome.
AB  - BACKGROUND: Visual acuity is known to be poorer in children with Down's syndrome
      than in age-matched controls. However, to date, clinicians do not have access to
      norms for children with Down's syndrome that allow differential discrimination of
      healthy from anomalous visual development in this population. METHODS: The Down's
      Syndrome Vision Research Unit at Cardiff University has been monitoring visual
      development in a large cohort of children since 1992. Cross-sectional data on
      binocular visual acuity were retrospectively analysed for 159 children up to 12
      years of age in order to establish binocular acuity norms. Longitudinal binocular
      acuity data were available for nine children who were seen regularly over the 12
      years age-range. Monocular acuity was successfully recorded less often in the
      cohort, but analysis of scores for 69 children allowed assessment of inter-ocular
      acuity differences and binocular summation. RESULTS: In comparison with published
      norms for the various acuity tests used, binocular acuity was consistently poorer
      in children with Down's syndrome from the age of three years and stabilised at
      around 0.25 logMAR from the age of four years. Inter-ocular acuity difference and
      binocular summation were both 0.06 logMAR, which is similar to the reported
      values in children without Down's syndrome. CONCLUSIONS: The study provides eye
      care practitioners with the expected values for binocular acuity in children with
      Down's syndrome and demonstrates the visual disadvantage that children with
      Down's syndrome have when compared with their typically developing peers. The
      results emphasise the responsibility that practitioners have to notify parents
      and educators of the relatively poor vision of children with Down's syndrome, and
      the need for classroom modifications.

PMID- 29601093
TI  - Cost-Effectiveness Analysis of Sacubitril/Valsartan for the Treatment of Heart
      Failure with Reduced Ejection Fraction in the United States.
AB  - OBJECTIVE: Sacubitril/valsartan (SAC/VAL) has been shown to reduce mortality and
      hospitalization in patients with heart failure with reduced ejection fraction
      (HFrEF) compared with enalapril but at a substantially higher cost. This study
      evaluates the cost-effectiveness of SAC/VAL versus enalapril in patients with
      HFrEF over a 5-year time horizon from the U.S. payer perspective. METHODS: A
      cohort-based Markov model was developed to compare costs and quality-adjusted
      life years (QALYs) between SAC/VAL and enalapril in patients with HFrEF over a 5
      year time horizon. Markov states included New York Heart Association (NYHA) class
      (II-IV) and death. Treatment discontinuation, HF-related hospitalizations, and
      NYHA class progression were modeled as transition states based on data from the
      PARADIGM trial. Other probabilities, costs, and utilities were obtained from
      published literature and public databases. RESULTS: In the base case analysis,
      SAC/VAL cost more than enalapril ($81,943 vs $67,287) and was more effective
      (2.647 QALYs vs 2.546 QALYs), resulting in an incremental cost-effectiveness
      ratio of $143,891/QALY gained. At a willingness to pay (WTP) of $100,000/QALY,
      SAC/VAL was cost-effective up to a cost of $298/month. Results were most
      sensitive to SAC/VAL cost, SAC/VAL mortality benefit, and NYHA progression
      probability. SAC/VAL had a 10% and 52% probability of being cost-effective at WTP
      thresholds of $100,000/QALY and $150,000/QALY, respectively. CONCLUSIONS: SAC/VAL
      is associated with clinical benefit and may be cost-effective compared with the
      current standard of care over realistic treatment durations from the payer
      perspective. Results of this analysis can inform discussions on the value and
      position of SAC/VAL in the current market.

PMID- 29601094
TI  - IL17A gene polymorphisms rs4711998 and rs8193036 are not associated with
      postbronchiolitis asthma in Finnish children.

PMID- 29601095
TI  - What's cold got to do with it? Cold-induced thermogenesis and microbiome
      modification may be regulated by bile acid physiology.

PMID- 29601096
TI  - Frontline Science: Elevated nuclear lamin A is permissive for granulocyte
      transendothelial migration but not for motility through collagen I barriers.
AB  - Transendothelial migration (TEM) of lymphocytes and neutrophils is associated
      with the ability of their deformable nuclei to displace endothelial cytoskeletal
      barriers. Lamin A is a key intermediate filament component of the nuclear lamina
      that is downregulated during granulopoiesis. When elevated, lamin A restricts
      nuclear squeezing through rigid confinements. To determine if the low lamin A
      expression by leukocyte nuclei is critical for their exceptional squeezing
      ability through endothelial barriers, we overexpressed this protein in
      granulocyte-like differentiated HL-60 cells. A 10-fold higher lamin A expression
      did not interfere with chemokinetic motility of these granulocytes on immobilized
      CXCL1. Furthermore, these lamin A high leukocytes exhibited normal chemotaxis
      toward CXCL1 determined in large pore transwell barriers, but poorly squeezed
      through 3 MUm pores toward identical CXCL1 gradients. Strikingly, however, these
      leukocytes successfully completed paracellular TEM across inflamed endothelial
      monolayers under shear flow, albeit with a small delay in nuclear squeezing into
      their sub-endothelial pseudopodia. In contrast, CXCR2 mediated granulocyte
      motility through collagen I barriers was dramatically delayed by lamin A
      overexpression due to a failure of lamin A high nuclei to translocate into the
      pseudopodia of the granulocytes. Collectively, our data predict that leukocytes
      maintain a low lamin A content in their nuclear lamina in order to optimize
      squeezing through extracellular collagen barriers but can tolerate high lamin A
      content when crossing the highly adaptable barriers presented by the endothelial
      cytoskeleton.

PMID- 29601097
TI  - pTRAPs: Transmembrane adaptors in innate immune signaling.
AB  - Transmembrane adaptor proteins (TRAPs) are protein scaffolds and signaling
      regulators with established roles in signal-induced activation of lymphocytes. A
      subset of the TRAP family, the palmitoylated TRAPs (pTRAPs), are increasingly
      emerging with additional roles in innate immune cells. Targeted to lipid rafts,
      tetraspannin-enriched microdomains, and protein microclusters in membranes, pTRAP
      scaffolds exert spatiotemporal regulation by recruiting signaling kinases,
      particularly Src and Syk family members, as well as Csk, and other effectors. In
      this way, pTRAPs modulate signaling and influence resulting cell responses,
      including the selective output of inflammatory cytokines and other mediators.
      Here, we review studies revealing that different pTRAPs work together, often with
      overlapping or redundant roles, for positive and negative regulation of key
      innate immune pathways, including Fc receptor and pattern recognition receptor
      signaling. Recent findings show that pTRAPs can bind directly to innate immune
      receptors, in addition to other transmembrane binding partners. Thus, pTRAPs are
      important, multifunctional scaffolds in pathways that are fundamental to diverse
      innate immune responses.

PMID- 29601098
TI  - Arylazopyrazole Photoswitches in Aqueous Solution: Substituent Effects,
      Photophysical Properties, and Host-Guest Chemistry.
AB  - Getting the green light! Substituted arylazopyrazoles (AAPs) have been
      investigated as supramolecular photoswitches in aqueous solution. Selective
      photostationary states (PSSs) and improved binding affinities to beta
      cyclodextrin have been determined. The experimental findings are supported by
      results from DFT calculations.

PMID- 29601099
TI  - Analytical validation of a flow cytometric protocol for quantification of
      platelet microparticles in dogs.
AB  - BACKGROUND: Platelet microparticles (PMPs) are subcellular procoagulant vesicles
      released upon platelet activation. In people with clinical diseases, alterations
      in PMP concentrations have been extensively investigated, but few canine studies
      exist. OBJECTIVES: This study aims to validate a canine flow cytometric protocol
      for PMP quantification and to assess the influence of calcium on PMP
      concentrations. METHODS: Microparticles (MP) were quantified in citrated whole
      blood (WB) and platelet-poor plasma (PPP) using flow cytometry. Anti-CD61
      antibody and Annexin V (AnV) were used to detect platelets and
      phosphatidylserine, respectively. In 13 healthy dogs, CD61+ /AnV- concentrations
      were analyzed with/without a calcium buffer. CD61+ /AnV- , CD61+ /AnV+ , and CD61
      /AnV+ MP quantification were validated in 10 healthy dogs. The coefficient of
      variation (CV) for duplicate (intra-assay) and parallel (inter-assay) analyses
      and detection limits (DLs) were calculated. RESULTS: CD61+ /AnV- concentrations
      were higher in calcium buffer; 841,800 MP/MUL (526,000-1,666,200) vs without;
      474,200 MP/MUL (278,800-997,500), P < .05. In WB, PMP were above DLs and
      demonstrated acceptable (<20%) intra-assay and inter-assay CVs in 9/10 dogs: 1.7%
      (0.5-8.9) and 9.0% (0.9-11.9), respectively, for CD61+ /AnV- and 2.4% (0.2-8.7)
      and 7.8% (0.0-12.8), respectively, for CD61+ /AnV+ . Acceptable CVs were not seen
      for the CD61- /AnV+ MP. In PPP, quantifications were challenged by high inter
      assay CV, overlapping DLs and hemolysis and lipemia interfered with
      quantification in 5/10 dogs. CONCLUSIONS: Calcium induced higher in vitro PMP
      concentrations, likely due to platelet activation. PMP concentrations were
      reliably quantified in WB, indicating the potential for clinical applications.
      PPP analyses were unreliable due to high inter-CV and DL overlap, and not
      obtainable due to hemolysis and lipemia interference.

PMID- 29601100
TI  - Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic
      Mechanism for GalNAc-Ts.
AB  - The family of polypeptide N-acetylgalactosamine (GalNAc) transferases (GalNAc-Ts)
      orchestrates the initiating step of mucin-type protein O-glycosylation by
      transfer of GalNAc moieties to serine and threonine residues in proteins.
      Deficiencies and dysregulation of GalNAc-T isoenzymes are related to different
      diseases. Recently, it has been demonstrated that an inactive GalNAc-T2 mutant
      (F104S), which is not located at the active site, induces low levels of high
      density lipoprotein cholesterol (HDL-C) in humans. Herein, the molecular basis
      for F104S mutant inactivation has been deciphered. Saturation transfer difference
      NMR spectroscopy experiments demonstrate that the mutation induces loss of
      binding to peptide substrates. Analysis of the crystal structure of the F104S
      mutant bound to UDP-GalNAc (UDP=uridine diphosphate), combined with molecular
      dynamics (MD) simulations, has revealed that the flexible loop is disordered and
      displays larger conformational changes in the mutant enzyme than that in the wild
      type (WT) enzyme. 19 F NMR spectroscopy experiments reveal that the WT enzyme
      only reaches the active state in the presence of UDP-GalNAc, which provides
      compelling evidence that GalNAc-T2 adopts a UDP-GalNAc-dependent induced-fit
      mechanism. The F104S mutation precludes the enzyme from achieving the active
      conformation and concomitantly binding peptide substrates. This study provides
      new insights into the catalytic mechanism of the large family of GalNAc-Ts and
      how these enzymes orchestrate protein O-glycosylation.

PMID- 29601102
TI  - Frontline Science: Specialized proresolving lipid mediators inhibit the priming
      and activation of the macrophage NLRP3 inflammasome.
AB  - The prototypic proinflammatory cytokine IL-1beta plays a central role in innate
      immunity and inflammatory disorders. The formation of mature IL-1beta from an
      inactive pro-IL-1beta precursor is produced via nonconventional multiprotein
      complexes called the inflammasomes, of which the most common is the nucleotide
      binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome
      composed by NLRP3, (ASC) apoptosis-associated speck-like protein containing a
      caspase activation and recruitment domain (CARD), and caspase-1. Specialized
      proresolving mediators (SPMs) promote resolution of inflammation, which is an
      essential process to maintain host health. SPMs prevent excessive inflammation by
      terminating the inflammatory response and returning to tissue homeostasis without
      immunosupression. This study tested the hypothesis that modulation of the NLRP3
      inflammasome in macrophages is one mechanism involved in the SPM-regulated
      processes during resolution. Our findings demonstrate that the SPM resolvin D2
      (RvD2) suppressed the expression of pro-IL-1beta and reduced the secretion of
      mature IL-1beta in bone marrow-derived macrophages challenged with LPS+ATP
      (classical NLRP3 inflammasome model) or LPS+palmitate (lipotoxic model). Similar
      findings were observed in thioglycolate-elicited peritoneal macrophages, in which
      RvD2 remarkably reduced ASC oligomerization, inflammasome assembly, and caspase-1
      activity. In vivo, in a self-resolving zymosan A-induced peritonitis model, RvD2
      blocked the NLRP3 inflammasome leading to reduced release of IL-1beta into the
      exudates, repression of osteopontin, and MCP-1 expression and induction of M2
      markers of resolution (i.e., CD206 and arginase-1) in peritoneal macrophages.
      RvD2 inhibitory actions were receptor mediated and were abrogated by a selective
      GPR18 antagonist. Together, these findings support the hypothesis that SPMs have
      the ability to inhibit the priming and to expedite the deactivation of the NLRP3
      inflammasome in macrophages during the resolution process.

PMID- 29601101
TI  - Regulation of immune cell signaling by activated protein C.
AB  - Innate immune cells are an essential part of the host defense response, promoting
      inflammation through release of proinflammatory cytokines or formation of
      neutrophil extracellular traps. While these processes are important for defense
      against infectious agents or injury, aberrant activation potentiates pathologic
      inflammatory disease. Thus, understanding regulatory mechanisms that limit
      neutrophil extracellular traps formation and cytokine release is of therapeutic
      interest for targeting pathologic diseases. Activated protein C is an endogenous
      serine protease with anticoagulant activity as well as anti-inflammatory and
      cytoprotective functions, the latter of which are mediated through binding cell
      surface receptors and inducing intracellular signaling. In this review, we
      discuss certain leukocyte functions, namely neutrophil extracellular traps
      formation and cytokine release, and the inhibition of these processes by
      activated protein C.

PMID- 29601103
TI  - Frontline Science: Characterization of a novel mouse strain expressing human
      Siglec-8 only on eosinophils.
AB  - Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a human cell surface
      protein expressed exclusively on eosinophils, mast cells, and basophils that,
      when engaged, induces eosinophil apoptosis and inhibits mast cell mediator
      release. This makes Siglec-8 a promising therapeutic target to treat diseases
      involving these cell types. However, preclinical studies of Siglec-8 targeting in
      vivo are lacking because this protein is only found in humans, apes, and some
      monkeys. Therefore, we have developed a mouse strain in which SIGLEC8
      transcription is activated by Cre recombinase and have crossed this mouse with
      the eoCre mouse to achieve eosinophil-specific expression. We confirmed that
      Siglec-8 is expressed exclusively on the surface of mature eosinophils in
      multiple tissues at levels comparable to those on human blood eosinophils.
      Following ovalbumin sensitization and airway challenge, Siglec-8 knock-in mice
      generated a pattern of allergic lung inflammation indistinguishable from that of
      littermate controls, suggesting that Siglec-8 expression within the eosinophil
      compartment does not alter allergic eosinophilic inflammation. Using bone marrow
      from these mice, we demonstrated that, during maturation, Siglec-8 expression
      occurs well before the late eosinophil developmental marker C-C motif chemokine
      receptor 3, consistent with eoCre expression. Antibody ligation of the receptor
      induces Siglec-8 endocytosis and alters the phosphotyrosine profile of these
      cells, indicative of productive signaling. Finally, we demonstrated that mouse
      eosinophils expressing Siglec-8 undergo cell death when the receptor is engaged,
      further evidence that Siglec-8 is functional on these cells. These mice should
      prove useful to investigate Siglec-8 biology and targeting in vivo in a variety
      of eosinophilic disease models.

PMID- 29601104
TI  - The impact of weight suppression and weight loss speed on baseline clinical
      characteristics and response to treatment.
AB  - OBJECTIVE: Growing evidence suggests an impact of weight suppression (WS) on
      severity and course of symptoms in patients with eating disorders (ED), but no
      study explored also the role of the weight loss speed (WLS) together with WS on
      the same clinical variables, which is the aim of the present work. METHOD: A
      mixed cross-sectional and longitudinal cohort study was employed. Four hundred
      and fourteen patients with anorexia nervosa (AN = 208) or bulimia nervosa (BN =
      206) according to DSM-5 criteria were recruited and assessed at referral by means
      of clinical interviews and self-reported questionnaires. Body mass index and
      diagnostic status were re-evaluated at the end of treatment. RESULTS: WS was
      positively correlated with body dissatisfaction in patients with AN (p = .005),
      but negatively correlated in BN (p = .022). In contrast, WLS was significantly
      inversely correlated with age and duration of illness in all ED (p < .001), and
      positively correlated with drive for thinness in BN (p = .007). After treatment,
      WS at intake predicted higher BMI increase in both AN and BN (p < .03), while
      higher WLS was significantly associated with a lower drop-out rate in patients
      with BN (p = .02), and predicted BMI increase only in restricting AN patients (p
      = .02). In the whole group, WLS significantly predicted remission status (p =
      .039). DISCUSSION: In our study, both WS and WLS were associated with baseline
      "core" clinical variables and provided complementary abilities to predict weight
      gain and remission at the end of treatment. If replicated, our data suggest the
      importance of considering both WS and WLS as useful clinical variables in the
      baseline assessment of ED.

PMID- 29601105
TI  - Efficacy and Safety of Rituximab for the Treatment of Graves' Orbitopathy: A Meta
      analysis of Randomized Controlled Trials.
AB  - STUDY OBJECTIVE: To investigate the efficacy and safety of rituximab in patients
      with Graves' orbitopathy (GO). DESIGN: Systematic review and meta-analysis of
      four randomized controlled trials. PATIENTS: A total of 293 patients with GO who
      received rituximab or control (either glucocorticoids, the established first-line
      therapy [three trials], or saline [one trial]). MEASUREMENTS AND RESULTS:
      Relevant studies published before February 2018 were identified from the PubMed,
      EMBASE, Cochrane Library, and Scopus databases and the ClinicalTrials.gov
      registry. Individual effect sizes were standardized, and a meta-analysis was
      conducted to calculate the pooled effect size by using a random-effects model.
      Treatment efficacy was assessed by measuring the following outcomes: clinical
      activity score (CAS), sight visual acuity reduction (NOSPECS) score, proptosis,
      diplopia, changes in eye volume, quality of life, and adverse events. In the four
      included trials, 113 patients in the rituximab group and 108 patients in the
      control group were evaluated. Compared with the control group, CAS (weighted mean
      difference 0.57, 95% confidence interval 0.25-0.89) was significantly reduced at
      24 weeks in the rituximab group. Compared with the control group, considerable
      proptosis reduction was also observed in the rituximab group; however, the
      difference was not significant. The proportion of adverse events in the rituximab
      group was not significantly higher than that in the glucocorticoid control group,
      but one of the included trials indicated that the rituximab group had more
      serious adverse events than the saline control group. CONCLUSION: Rituximab is a
      relatively safe and viable treatment that is superior to glucocorticoids or
      saline for patients with moderate to severe GO. However, the incidence of serious
      adverse events was disparate among the included trials. Additional studies
      involving a larger sample size and investigating the optimal rituximab dosage,
      frequency, and method of administration are warranted.

PMID- 29601106
TI  - Skin temperature in youth soccer players with functional equinus and non-equinus
      condition after running.
AB  - OBJECTIVES: To check how a thermal IR camera can check skin temperature in
      gastrocnemius-soleus equinus condition and non-gastrocnemius-soleus condition in
      youth soccer players and thus detect association between the extensibility of the
      triceps surae (with gastrocnemius-soleus equinus and non-gastrocnemius-soleus
      equinus) and the muscle temperature pattern. DESIGN: A cross-sectional study
      secondary level of care. METHODS: Sample from an elite soccer academy in Madrid
      (Spain) 35 healthy male subjects (youth soccer players) age 12.82 +/- 1.07 years,
      height 158.68 +/- 10.79 cm, weight 49.19 +/- 9.45 kg, body mass index 19.41 +/-
      2.25. The exclusion criteria were the presence of musculoskeletal and joint
      injuries, pelvic pain, ankle sprains, low back pain and use of drugs in the
      previous week, and scoliosis. RESULTS: Temperature value for gastrocnemius
      muscles and Achilles tendon were assessed in 35 youth soccer players from an
      academia before and after training in both 12 gastrocnemius-soleus equinus and 23
      non-gastrocnemius-soleus equinus soccer players conditions. State absolute for
      gastrocnemius soleus condition obtained a 0.34 value (0.19-0.5); we found a
      significant increase in temperature among these conditions for the gastrocnemius
      (P = 0.028) and the Achilles tendon (P = 0.007) (confidence interval 95%). The
      temperature of gastrocnemius-soleus equinus for gastrocnemius and Achilles tendon
      was increased more than non-gastrocnemius-soleus equinus in youth soccer players.
      CONCLUSIONS: IR imaging captured temperature is associated with muscle pattern
      activation for lower limb. Based on our findings, we propose that infrared
      thermography evaluation of the gastrocnemius and Achilles tendon is suitable to
      differ gastrocnemius-soleus equinus and non-gastrocnemius-soleus equinus
      conditions in youth soccer players.

PMID- 29601107
TI  - Characterization of a chimeric chemokine as a specific ligand for ACKR3.
AB  - Chemokines, small chemotactic cytokines, orchestrate cell migration by binding to
      their cognate chemokine receptors. While chemokine-mediated stimulation of
      typical G-protein-coupled chemokine receptors leads to cell migration, binding of
      chemokines to atypical chemokine receptors (ACKRs) does not induce canonical
      signaling. ACKRs are considered important chemokine scavengers, that can create
      gradients which help direct cells to sites of inflammation or to their
      immunological niches. Synthetic chemokines have been used in the past to study
      and decode chemokine-receptor interactions. Characterizing specific chemokine
      ACKRs interactions is challenging because the chemokines bind multiple receptors;
      for example, the ACKR3 ligands CXCL12 and CXCL11 bind to the canonical receptors
      CXCR4 and CXCR3, respectively. Here, we present the engineering of a chemokine
      like chimera, which selectively binds to ACKR3. The addition of a ybbR13 tag at
      the C-terminus allows site specific enzymatic labeling with a plethora of
      fluorescent dyes. The chimera is composed of the N-terminus of CXCL11 and the
      main body and C-terminus of CXCL12 and selectively interacts with ACKR3 with high
      affinity, while not interfering with binding of CXCL11 and CXCL12 to their
      cognate receptors. We further provide evidence that the chimera can be used to
      study ACKR3 function in vivo.

PMID- 29601108
TI  - Synthesis of Avibactam Derivatives and Activity on beta-Lactamases and
      Peptidoglycan Biosynthesis Enzymes of Mycobacteria.
AB  - There is a renewed interest for beta-lactams for treating infections due to
      Mycobacterium tuberculosis and M. abscessus because their beta-lactamases are
      inhibited by classical (clavulanate) or new generation (avibactam) inhibitors,
      respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO)
      scaffold of avibactam for functionalization by the Huisgen-Sharpless
      cycloaddition reaction is reported. The amoxicillin-DBO combinations were active,
      indicating that the triazole ring is compatible with drug penetration (minimal
      inhibitory concentration of 16 MUg mL-1 for both species). Mechanistically, beta
      lactamase inhibition was not sufficient to account for the potentiation of
      amoxicillin by DBOs. Thus, the latter compounds were investigated as inhibitors
      of l,d-transpeptidases (Ldts), which are the main peptidoglycan polymerases in
      mycobacteria. The DBOs acted as slow-binding inhibitors of Ldts by S
      carbamoylation indicating that optimization of DBOs for Ldt inhibition is an
      attractive strategy to obtain drugs selectively active on mycobacteria.

PMID- 29601109
TI  - Fungal diseases in children and adolescents in a referral centre in Bogota,
      Colombia.
AB  - A cross-sectional descriptive study was conducted at a dermatology referral
      centre in Bogota, to estimate the frequencies and aetiologies of mycoses in the
      population under 18 years of age attending the medical mycology laboratory over a
      13-year period (2000-2012). A total of 1337 samples from 1221 patients were
      evaluated, involving direct examination and culture for 1279 samples, direct
      examination alone for 50 and culture alone for 8. During the study period,
      dermatophytosis was diagnosed via culture in 537 cases (40.1%). The most common
      aetiological agents were Trichophyton rubrum (235 cases), Microsporum canis
      (177), Trichophyton mentagrophytes (74) and Microsporum gypseum (22). Pityriasis
      versicolor was found in 31 cases (5.1%), Candida spp. were found in 17 cases, and
      non-dermatophyte moulds were confirmed by a second sample in 6 cases (3 cases
      involving Fusarium spp., 2 Neoscytalidium dimidiatum and 1 Acremonium spp.). In
      addition, white piedra was diagnosed in 4 cases (0.7%), and tinea nigra in 2
      cases (0.3%). Regarding subcutaneous mycoses, 14 cases of sporotrichosis were
      identified. The results from this study confirm the predominance of
      dermatophytosis in the paediatric population. T. rubrum and M. canis were the
      main aetiological agents. We found a few cases of onychomycosis by non
      dermatophyte moulds. Sporotrichosis was the only subcutaneous mycosis diagnosed
      during the study period.

PMID- 29601112
TI  - Cerebral perfusion characteristics show differences in younger versus older
      children with sickle cell anaemia: Results from a multiple-inflow-time arterial
      spin labelling study.
AB  - Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen
      desaturation, which elevate cerebral blood flow (CBF) and increase the risk of
      neurocognitive complications. Arterial spin labelling (ASL) provides a
      methodology for measuring CBF non-invasively; however, ASL techniques using only
      a single inflow time are not sufficient to fully characterize abnormal
      haemodynamic behaviour in SCA. This study investigated haemodynamic parameters
      from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18
      years) children with SCA with and without silent cerebral infarction (SCI+/-) (n
      = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9
      and 7 respectively). Compared with controls, CBF was elevated globally in both
      groups of patients. In the younger SCA patients, blood oxygen content was
      negatively correlated with CBF in the middle and posterior cerebral artery
      territories and significantly positively correlated with bolus arrival time (BAT)
      in the anterior and middle cerebral artery territories. In older children, SCA
      patients had significantly shorter BAT than healthy controls and there was a
      significant negative correlation between CBF and oxygen content only in the
      territory of the posterior cerebral artery, with a trend for a correlation in the
      anterior cerebral artery but no relationship for the middle cerebral artery
      territory. In the younger group, SCI+ patients had significantly higher CBF in
      the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI-
      mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached
      significance when two children with abnormal transcranial Doppler and one with
      haemoglobin SC disease were excluded, and there were no significant differences
      between patients with and without SCI in the older children. With age, there
      appears to be increasing disparity between patients and controls in terms of the
      relationship between CBF and oxygen content in the anterior circulation,
      potentially predicting the risk of acute and chronic compromise of brain tissue.

PMID- 29601110
TI  - Expression of novel "LOCGEF" isoforms of ARHGEF18 in eosinophils.
AB  - Genomic, transcriptomic and proteomic databases indicate that the N-terminal 322
      residues encoded by the presumptive LOC100996504 gene, which is adjacent to the
      ARHGEF18 guanine nucleotide exchange factor gene on chromosome 19, constitute the
      N-terminal portion of a 1361-residue isoform of ARHGEF18, dubbed LOCGEF-X3.
      LOCGEF-X3 arises from the use of a leukocyte-specific alternative transcriptional
      start site and splicing that bypasses the initial noncoding exon of the canonical
      1015-residue ARHGEF18 isoform, p114. Eosinophil LOCGEF-X3 was amplified and
      cloned, recombinant LOCGEF-X3 was expressed, and anti-ARHGEF18 antibody was found
      to recognize a band in immunoblots of eosinophil lysates that co-migrates with
      recombinant LOCGEF-X3. PCR of eosinophils revealed minor amounts of transcripts
      for X4 and X5 isoforms of LOCGEF that arise from differential splicing and differ
      from the X3 isoform at their extreme N-termini. No p114 transcript or protein
      band was detected in eosinophils. Immunostaining with anti-ARHGEF18 antibody
      revealed relocalization of LOCGEF and RHOA from the periphery of round
      unstimulated eosinophils to the 2 poles of eosinophils polarized by treatment
      with IL5, CCL11, or IL33 in suspension. Canonical p114 ARHGEF18 has been
      implicated in maintenance of epithelial cell polarity. We suggest that the "LOC"
      portion of LOCGEF, which is unlike any other protein domain, has unique functions
      in control of polarity in activated eosinophils and other leukocytes.

PMID- 29601111
TI  - Oscillating gradient diffusion kurtosis imaging of normal and injured mouse
      brains.
AB  - Recent advances in diffusion MRI employ multiple diffusion encoding schemes with
      varying diffusion direction, weighting, and diffusion time to investigate
      specific microstructural properties in biological tissues. In this study, we
      examined time-dependent diffusion kurtosis contrast in adult mouse brains and in
      neonatal mouse brains after hypoxic-ischemic (HI) injury. In vivo diffusion
      kurtosis maps were acquired with a short diffusion time using an oscillating
      gradient spin echo (OGSE) sequence at 100 Hz and with a relatively long diffusion
      time (20 ms) using a pulsed gradient spin echo (PGSE) sequence. In the adult
      mouse brain, we found that the cortex and hippocampus showed larger differences
      between OGSE kurtosis and PGSE kurtosis than major white matter tracts. In
      neonatal mouse brains with unilateral HI injury, the OGSE kurtosis map overall
      provided stronger edema contrast than the PGSE kurtosis map, and the differences
      between OGSE and PGSE kurtosis measurements in the edema region reflected
      heterogeneity of injury. This is the first in vivo study that has demonstrated
      multi-direction OGSE kurtosis contrasts in the mouse brain. Comparing PGSE and
      OGSE kurtosis measures may provide additional information on microstructural
      changes after ischemic stroke.

PMID- 29601113
TI  - Directional Self-Sorting with Cucurbit[8]uril Controlled by Allosteric pi-pi and
      Metal-Metal Interactions.
AB  - To maximize Coulombic interactions, cucurbit[8]uril (CB[8]) typically forms
      ternary complexes that distribute the positive charges of the pair of guests (if
      any) over both carbonylated portals of the macrocycle. We present here the first
      exception to this recognition pattern. Platinum(II) acetylides flanked by 4'
      substituted terpyridyl ligands (tpy) form 2:1 complexes with CB[8] in an
      exclusively stacked head-to-head orientation in a water/acetonitrile mixture. The
      host encapsulates the pair of tpy substituents, and both positive Pt centers sit
      on top of each other at the same CB[8] rim, leaving the other rim free of any
      interaction with the guests. This dramatic charge imbalance between the CB[8]
      rims would be electrostatically penalizing, were it not for allosteric pi-pi
      interactions between the stacked tpy ligands, and possible metal-metal
      interactions between both Pt centers. When both tpy and acetylides are
      substituted with aryl units, the metal-ligand complexes form 2:2 assemblies with
      CB[8] in aqueous medium, and the directionality of the assembly (head-to-head or
      head-to-tail) can be controlled, both kinetically and thermodynamically.

PMID- 29601114
TI  - Analysis and improvement of motion encoding in magnetic resonance elastography.
AB  - Magnetic resonance elastography (MRE) utilizes phase contrast magnetic resonance
      imaging (MRI), which is phase locked to externally generated mechanical
      vibrations, to measure the three-dimensional wave displacement field. At least
      four measurements with linear-independent encoding directions are necessary to
      correct for spurious phase contributions if effects from imaging gradients are
      non-negligible. In MRE, three encoding schemes have been used: unbalanced four-
      and six-point and balanced four-point ('tetrahedral') encoding. The first two
      sensitize to motion with orthogonal gradients, with the four-point method
      acquiring a single reference scan without motion sensitization, whereas three
      additional scans with inverted gradients are used with six-point encoding,
      leading to two-fold higher displacement-to-noise ratio (DNR) and 50% longer scan
      duration. Balanced four-point (tetrahedral) encoding encodes along the four
      diagonals of a cube, with one direction serving as a reference for the other
      three encoding directions, similar to four-point encoding. The objective of this
      work is to introduce a theoretical framework to compare different motion
      sensitization strategies with respect to their motion encoding efficiency in two
      fundamental encoding limits, the gradient strength limit and the dynamic range
      limit, which are both placed in relation to conventional gradient recalled echo
      (GRE)- and spin echo (SE)-based MRE sequences. We apply the framework to the
      three aforementioned schemes and show that the motion encoding efficiency of
      unbalanced four- and six-point encoding schemes in the gradient-limited regime
      can be increased by a factor of 1.5 when using all physical gradient channels
      concurrently. Furthermore, it is demonstrated that reversing the direction of the
      reference in balanced four-point (tetrahedral) encoding results in the Hadamard
      encoding scheme, which leads to increased DNR by 2 compared with balanced four
      point encoding and 2.8 compared with unbalanced four-point encoding. As an
      example, we show that optimal encoding can be utilized to reduce the acquisition
      time of standard liver MRE in vivo from four to two breath holds.

PMID- 29601116
TI  - Spotlights are papers selected by editors published in peer-reviewed journals
      that may be more regionally specific or appearing in languages other than
      English.

PMID- 29601115
TI  - Long-Term Beta-Blocker Therapy after Myocardial Infarction in the Reperfusion
      Era: A Systematic Review.
AB  - Beta-blockers are recommended as standard of care for patients who experience a
      myocardial infarction (MI). However, evidence to support this recommendation is
      primarily derived from the pre-reperfusion era. In the reperfusion era, short
      term (<= 30 days) beta-blocker therapy has been demonstrated to reduce recurrent
      MI and angina, but not mortality. The objective of this review was to evaluate
      the evidence for long-term (>= 1 yr) beta-blocker therapy in patients post-MI
      without left ventricular dysfunction in the reperfusion era. A systematic search
      of MEDLINE, EMBASE, CENTRAL, and Google from inception to September 2017 was
      performed. Included were randomized controlled trials and observational
      propensity score cohort studies published within the past 10 years that compared
      beta-blockers to placebo/no beta-blockers at discharge in patients with an acute
      MI but without left ventricular dysfunction or heart failure. Outcomes of
      interest included all-cause and cardiovascular mortality, nonfatal MI, and
      nonfatal stroke. Eight cohort studies were included. Follow-up ranged from 1 to 5
      years. Two smaller studies demonstrated a reduction in all-cause mortality with
      beta-blockers, whereas there was no difference observed in six studies. One study
      showed reduced cardiovascular mortality at 1 year, but no difference in sudden
      cardiac death. One study demonstrated a reduction in cardiac mortality at 3
      years, but no difference in MI or stroke. None of the four studies that reported
      adverse cardiovascular events demonstrated a benefit with beta-blocker therapy.
      Though these data are limited by observational methodology, the majority of the
      included studies failed to demonstrate a benefit in survival or cardiovascular
      events with long-term beta-blockers in post-MI patients with normal left
      ventricular function. In the absence of a contemporary randomized controlled
      trial, this evidence imparts uncertainty regarding the current standard of care
      and suggests that it may be reasonable to discontinue beta-blockers in patients
      without impaired left ventricular function at 1-year post-MI who do not have
      another indication for use.

PMID- 29601117
TI  - The legacy of Adam Johnson.

PMID- 29601118
TI  - Side Methyl Groups Control the Conformation and Contribute to Symmetry Breaking
      of Isoprenoid Chromophores.
AB  - Ab initio DFT computations reveal that the essential structural and photophysical
      features of the conjugated pi-electron system of retinal and carotenoids are
      dictated by "innocent" methyl substituents. These methyl groups shape the
      conformation and symmetry of the isoprenoid chromophores by causing a sigmoidal
      distortion of the polyene skeleton and increasing its flexibility, which
      facilitates fitting to their binding pockets in proteins. Comparison of in vacuo
      conformations of the chromophores with their native (protein-bound) conformations
      showed, surprisingly, that the peripheral groups and interactions with the
      protein environment are much less significant than the methyl side groups in
      tuning their structural features. The methyl side groups also contribute to a
      loss of symmetry elements specific to linear polyenes. In effect, the symmetry
      imposed restrictions on the chromophore electronic properties are disabled, which
      is of tremendous relevance to their photophysics. This is evidenced by their non
      negligible permanent dipole moments and by the simulated and experimentally
      measured circular dichroism spectra, which necessarily reflect the chirality of
      the conjugated pi-electron system.

PMID- 29601119
TI  - Employing an Unsaturated Th4+ Site in a Porous Thorium-Organic Framework for
      Kr/Xe Uptake and Separation.
AB  - Actinide based metal-organic frameworks (MOFs) are unique not only because
      compared to the transition-metal and lanthanide systems they are substantially
      less explored, but also owing to the uniqueness of actinide ions in bonding and
      coordination. Now a 3D thorium-organic framework (SCU-11) contains a series of
      cages with an effective size of ca. 21*24 A. Th4+ in SCU-11 is 10-coordinate with
      a bicapped square prism coordination geometry, which has never been documented
      for any metal cation complexes. The bicapped position is occupied by two
      coordinated water molecules that can be removed to afford a very unique open Th4+
      site, confirmed by X-ray diffraction, color change, thermogravimetry, and
      spectroscopy. The degassed phase (SCU-11-A) exhibits a Brunauer-Emmett-Teller
      surface area of 1272 m2  g-1 , one of the highest values among reported actinide
      materials, enabling it to sufficiently retain water vapor, Kr, and Xe with uptake
      capacities of 234 cm3  g-1 , 0.77 mmol g-1 , 3.17 mmol g-1 , respectively, and a
      Xe/Kr selectivity of 5.7.

PMID- 29601120
TI  - Increased centrosome number in BRCA-related breast cancer specimens determined by
      immunofluorescence analysis.
AB  - BRCA-related breast carcinoma can be prevented through prophylactic surgery and
      an intensive follow-up regimen. However, BRCA genetic tests cannot be routinely
      performed, and some BRCA mutations could not be defined as deleterious mutations
      or normal variants. Therefore, an easy functional assay of BRCA will be useful to
      evaluate BRCA status. As it has been reported that BRCA functions in the
      regulation of centrosome number, we focused on centrosome number in cancer
      tissues. Here, 70 breast cancer specimens with known BRCA status were analyzed
      using immunofluorescence of gamma-tubulin (a marker of centrosome) foci. The
      number of foci per cell was higher in cases with BRCA mutation compared to wild
      type cases, that is, 1.9 (95% confidence interval [CI], 1.5-2.3) vs 0.5 (95% CI,
      0.2-0.8) (P < .001). Specifically, foci numbers per cell in BRCA1 and BRCA2
      mutation cases were 1.2 (95% CI, 0.6-1.8) and 2.2 (95% CI, 1.7-2.6),
      respectively, both higher than those in wild-type cases (P = .042 and P < .0001,
      respectively). The predictive value of gamma-tubulin foci as determined by area
      under the curve (AUC = 0.86) for BRCA status was superior to BRCAPRO (AUC =
      0.69), Myriad Table (AUC = 0.61), and KOHBRA BRCA risk calculator (AUC = 0.65)
      pretest values. The use of gamma-tubulin foci to predict BRCA status had
      sensitivity = 83% (19/23), specificity = 89% (42/47), and positive predictive
      value = 77% (20/26). Thus, gamma-tubulin immunofluorescence, a functional
      assessment of BRCA, can be used as a new prospective test of BRCA status.

PMID- 29601121
TI  - PAI-1 induces Src inhibitor resistance via CCL5 in HER2-positive breast cancer
      cells.
AB  - Tyrosine kinase Src is overexpressed and activated in various tumors, including
      breast cancer, and is supposed to promote cancer formation and development. Src
      inhibitors have been developed recently and have shown efficacy in breast cancer
      as a single agent or in combination with anti-HER2 antibodies or chemotherapy.
      Unfortunately, the potency of Src inhibitor is limited by the development of drug
      resistance. In our study, we established an Src inhibitor saracatinib-resistant
      breast cancer cell line (SKBR-3/SI) for the first time and by evaluating mRNA
      expression profile, we found that plasminogen activator inhibitor-1 (PAI-1) was
      upregulated in saracatinib-resistant cells compared to the parent cells. Further
      study demonstrated that PAI-1 might induce saracatinib resistance in breast
      cancer cells by increasing the secretion of chemokine (C-C motif) ligand 5
      (CCL5). Functional assays showed that PAI-1 and CCL5 overexpression promoted cell
      proliferation and migration in breast cancer cells, while inhibition of PAI-1 and
      CCL5 decreased cell proliferation and migration in saracatinib-resistant cells.
      We also showed that targeting PAI-1 or CCL5 could reverse saracatinib resistance,
      which deserves more attention in clinical settings.

PMID- 29601122
TI  - Oncologic outcomes of surgical treatment for T3 glottic laryngeal squamous cell
      carcinoma.
AB  - BACKGROUND: The purpose of this study was to assess the clinical results of
      patients with T3 glottic laryngeal carcinoma treated with total laryngectomy or
      partial laryngectomy. METHODS: We conducted a retrospectively review of 307
      patients with T3 glottic laryngeal squamous cell carcinoma (SCC). RESULTS: The 5
      year cancer-specific survival (CSS) rate was 71.5% and the overall survival (OS)
      rate was 70.6%. For patients who underwent total laryngectomy, the 5-year disease
      free survival (DFS) rate was 59.8%, and the CSS rate was 67.9%. For partial
      laryngectomy, the 5-year DFS rate was 64.8%, and the CSS rate was 78.0%. High
      lymph node and stage status are predictors of mortality for these patients. No
      difference was found in DFS and CSS rates between patients with negative margins
      and those with positive margins after postoperative radiotherapy and
      chemotherapy. CONCLUSION: Postoperative radiotherapy and chemotherapy are
      effective treatments for patients with T3 glottic laryngeal carcinoma, especially
      with a positive margin. For selected patients with T3 glottic laryngeal
      carcinoma, partial laryngectomy is a good choice because it can achieve
      satisfactory oncologic results while preserving laryngeal function.

PMID- 29601124
TI  - Monitoring of the ADP/ATP Ratio by Induced Circularly Polarised Europium
      Luminescence.
AB  - A series of three europium complexes bearing picolyl amine moieties was found to
      possess differing binding affinities towards Zn2+ and three nucleotides: AMP,
      ADP, and ATP. A large increase in the total emission intensity was observed upon
      binding Zn2+ , followed by signal amplification upon the addition of nucleotides.
      The resulting adducts possessed strong induced circularly polarised emission,
      with ADP and ATP signals of opposite sign. Model DFT geometries of the adducts
      suggest the Delta diastereoisomer is preferred for ATP and the Lambda isomer for
      ADP/AMP. This change in sign allows the ADP/ATP (or AMP/ATP) ratio to be assessed
      by monitoring changes in the emission dissymmetry factor, gem .

PMID- 29601125
TI  - Modified High-Nickel Cathodes with Stable Surface Chemistry Against Ambient Air
      for Lithium-Ion Batteries.
AB  - High-Ni layered oxides are promising next-generation cathodes for lithium-ion
      batteries owing to their high capacity and lower cost. However, as the Ni content
      increases over 70 %, they have a high dynamic affinity towards moisture and CO2
      in ambient air, primarily reacting to form LiOH, Li2 CO3 , and LiHCO3 on the
      surface, which is commonly termed "residual lithium". Air exposure occurs after
      synthesis as it is common practice to handle and store them under ambient
      conditions. The air exposure leads to significant performance losses, and hampers
      the electrode fabrication, impeding their practical viability. Herein, we show
      that substituting a small amount of Al for Ni in the crystal lattice notably
      improves the chemical stability against air by limiting the formation of LiOH,
      Li2 CO3 , LiHCO3 , and NiO in the near-surface region. The Al-doped high-Ni
      oxides display a high capacity retention with excellent rate capability and
      cycling stability after being exposed to air for 30 days.

PMID- 29601123
TI  - Hydrogen sulfide in physiology and pathogenesis of bacteria and viruses.
AB  - An increasing number of studies have established hydrogen sulfide (H2 S) gas as a
      major cytoprotectant and redox modulator. Following its discovery, H2 S has been
      found to have pleiotropic effects on physiology and human health. H2 S acts as a
      gasotransmitter and exerts its influence on gastrointestinal, neuronal,
      cardiovascular, respiratory, renal, and hepatic systems. Recent discoveries have
      clearly indicated the importance of H2 S in regulating vasorelaxation,
      angiogenesis, apoptosis, ageing, and metabolism. Contrary to studies in higher
      organisms, the role of H2 S in the pathophysiology of infectious agents such as
      bacteria and viruses has been less studied. Bacterial and viral infections are
      often accompanied by changes in the redox physiology of both the host and the
      pathogen. Emerging studies indicate that bacterial-derived H2 S constitutes a
      defense system against antibiotics and oxidative stress. The H2 S signaling
      pathway also seems to interfere with redox-based events affected on infection
      with viruses. This review aims to summarize recent advances on the emerging role
      of H2 S gas in the bacterial physiology and viral infections. Such studies have
      opened up new research avenues exploiting H2 S as a potential therapeutic
      intervention. (c) 2018 The Authors IUBMB Life published by Wiley Periodicals,
      Inc. on behalf of International Union of Biochemistry and Molecular Biology,
      70(5):393-410, 2018.

PMID- 29601126
TI  - Expression of cytosolic malic enzyme (ME1) is associated with disease progression
      in human oral squamous cell carcinoma.
AB  - Malic enzyme 1 (ME1) is a multifunctional protein involved in glycolysis, the
      citric acid cycle, NADPH production, glutamine metabolism, and lipogenesis. It is
      overexpressed in various cancers. We examined the expression of ME1 in 119 oral
      squamous cell carcinomas (OSCCs) using immunohistochemistry. Malic enzyme 1
      expression was moderate to strong in 57 (48%) OSCCs and correlated with pT, pN,
      clinical stage, and histological grade. In 37 cases with prognostic evaluation,
      moderate to strong ME1 expression indicated a worse prognosis than did weak ME1
      expression. Malic enzyme 1 knockdown or inactivation by lanthanide inhibited cell
      proliferation and motility and suppressed the epithelial-mesenchymal transition
      in HSC3 human OSCC cells. Knockdown of ME1 also shifted energy metabolism from
      aerobic glycolysis and lactate fermentation to mitochondrial oxidative
      phosphorylation, and the redox status from reductive to oxidative. In a mouse
      tumor model, lanthanide suppressed tumor growth and increased survival time.
      These findings reveal that ME1 is a valid target for molecular therapy in OSCC.

PMID- 29601128
TI  - Medical student enquiries on the art of clinical inertia.

PMID- 29601129
TI  - Effect of histone deacetylase inhibitor on epithelial-mesenchymal transition of
      liver fibrosis.
AB  - Liver fibrosis is an excessively reversible wound healing process and the
      fibrotic disorder is the activation of hepatic stellate cell that requires
      extensive alterations in gene expression. As reversible deacetylation of histone
      proteins modulate gene expression, we examined the effect of valproic acid (VPA)
      as selective histone deacetylase inhibitor on CCl-4 induced liver fibrosis.
      Thirty rats were divided into three equal groups; control group, fibrotic group
      and VPA-treated group. The rats were sacrificed after 6 weeks of liver fibrosis
      induction. The histopathological effect on liver tissue was examined. The
      expression of alpha-SMA and Smad-4 mRNA and serum levels of TGF-beta1, alanine
      aminotransferase, and aspartate aminotransferase were determined. Treatment of
      rats with VPA attenuated carbon tetrachloride-induced liver fibrosis. Moreover,
      alpha-SMA and Smad-4 expression was repressed under VPA treatment and both serum
      TGF-beta1 and liver enzymes were significantly decreased. The histone deacetylase
      inhibitor-1 VPA inhibits the epithelial-mesenchymal transition and affects
      hepatic stellate cell activation during liver fibrosis through downregulation of
      Smad4 and alpha-SMA expression which may serve as a promising agent in liver
      fibrosis treatment. (c) 2018 IUBMB Life, 70(6):511-518, 2018.

PMID- 29601127
TI  - LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in
      response to metformin treatment.
AB  - Metastasis to distant organs is a particularly ominous feature of malignant
      cancer. LKB1 (also known as STK11) has been identified as a tumor suppressor in
      several types of cancers. Here, we show that LKB1 is at low levels and is
      negatively associated with poor clinical outcomes in pancreatic cancer (PC). LKB1
      is inversely correlated with Snail protein in PC, in which the loss of LKB1
      facilitates metastasis through elevating Snail protein level. Furthermore, LKB1
      boosts Snail's interaction with E3 ligase FBXL14, leading to increasing ubiquitin
      mediated Snail degradation. Notably, metformin could increase Snail protein
      ubiquitination via augmenting the location of LKB1 at cytoplasm as well as
      increasing LKB1 expression. Altogether, our data established that LKB1 impedes
      invasion and metastasis by decreasing the Snail protein level in PC. Targeting
      the LKB1/FBXL14/Snail axis may represent a promising therapeutic strategy and
      metformin might be beneficial for PC therapy through activating the LKB1-mediated
      Snail ubiquitination pathway.

PMID- 29601130
TI  - Halogen-Aromatic pi Interactions Modulate Inhibitor Residence Times.
AB  - Prolonged drug residence times may result in longer-lasting drug efficacy,
      improved pharmacodynamic properties, and "kinetic selectivity" over off-targets
      with high drug dissociation rates. However, few strategies have been elaborated
      to rationally modulate drug residence time and thereby to integrate this key
      property into the drug development process. Herein, we show that the interaction
      between a halogen moiety on an inhibitor and an aromatic residue in the target
      protein can significantly increase inhibitor residence time. By using the
      interaction of the serine/threonine kinase haspin with 5-iodotubercidin (5-iTU)
      derivatives as a model for an archetypal active-state (type I) kinase-inhibitor
      binding mode, we demonstrate that inhibitor residence times markedly increase
      with the size and polarizability of the halogen atom. The halogen-aromatic pi
      interactions in the haspin-inhibitor complexes were characterized by means of
      kinetic, thermodynamic, and structural measurements along with binding-energy
      calculations.

PMID- 29601131
TI  - Pathological tumor regression grade of metastatic tumors in lymph node predicts
      prognosis in esophageal cancer patients.
AB  - Tumor regression grade of the primary tumor (TRG-PT) and residual lymph node
      metastasis have been pathologically determined in esophageal squamous cell
      carcinoma (ESCC) patients who had received neoadjuvant chemotherapy (nCT)
      followed by surgery; however, TRG of the metastatic tumor involving lymph nodes
      (LN) has not yet been determined. The aim of the present study was to clarify the
      impact of TRG on the prognosis of ESCC patients. ESCC patients (n = 110) who had
      received nCT followed by surgery were enrolled. Dissected LN were classified into
      2 categories: plausible positive metastatic LN (pp-MLN) where viable and/or
      degenerated ESCC cells and/or tissue modifications were observed, and non
      metastatic LN (non-MLN) where neither of them was observed. We defined nCT
      effective rate (CER) as the ratio of the number of pp-MLN that showed tumor
      regression to the total number of pp-MLN, and divided CER into low-CER (LCER;
      >=0% and <50%) and high-CER (HCER; >=50% and <=100%). Relationships between CER
      and clinicopathological factors including prognosis were then examined.
      Multivariate analyses of 110 patients indicated that ypT3-4 (P = .023, HR;
      2.551), positive venous infiltration (P = .006, HR; 3.526), and LCER (P = .033,
      HR; 1.922) were independently associated with shorter recurrence-free survival
      (RFS). Multivariate analyses of 43 patients with grade 0 TRG-PT showed that ypT3
      4 (P = .033, HR; 3.397) and LCER (P = .008, HR; 3.543) were independently
      associated with shorter RFS. This study showed that CER was one of the prognostic
      factors for ESCC patients who had received nCT followed by surgery.

PMID- 29601132
TI  - Full Conformational Landscape of 3-Methoxyphenol Revealed by Room Temperature mm
      wave Rotational Spectroscopy Supported by Quantum Chemical Calculations.
AB  - Room temperature millimeter-wave rotational spectroscopy supported by high level
      of theory calculations have been employed to fully characterise the
      conformational landscape of 3-Methoxyphenol, a semi-volatile polar oxygenated
      aromatic compound precursor of secondary organic aerosols in the atmosphere
      arising from biomass combustion. While previous rotationally-resolved
      spectroscopic studies in the microwave and in the UV domains failed to observe
      the complete conformational landscape, the 70-330 GHz rotational spectrum
      measured in this study reveals the ground state rotational signatures of the four
      stable conformations theoretically predicted. Moreover, rotational transitions in
      the lowest energy vibrationally excited states were assigned for two conformers.
      While the inertial defect of methoxyphenol does not significantly change between
      conformers and isomers, the excitation of the methoxy out-of-plane bending is the
      main contribution to the non-planarity of the molecule.

PMID- 29601133
TI  - All-Optical Switching and Two-States Light-Controlled Coherent-Incoherent Random
      Lasing in a Thiophene-Based Donor-Acceptor System.
AB  - We describe herein the synthesis and characterization of a thiophene-based donor
      acceptor system, namely (E)-2-(4-nitrostyryl)-5-phenylthiophene (Th-pNO2 ), which
      was prepared under Horner-Wadsworth-Emmons conditions. The UV/Vis absorption
      bands, including the intramolecular charge transfer (ICT) band, were fully
      assigned using DFT and TD-DFT computations. The results of both efficient third
      order nonlinear optical properties and light-amplification phenomena are
      presented. Investigations of photoinduced birefringence (PIB) in optical Kerr
      effect (OKE) experiments showed a great potential for this particular compound as
      an efficient, fully reversible, and fast optical switch. Time constants for the
      observed trans-cis-trans molecular transitions are in the range of microseconds
      and give a competitive experimental result for the well-known and exploited
      azobenzene derivatives. Random lasing (RL) investigations confirmed that this
      organic system is potentially useful to achieve strong light enhancement,
      observed as a multimode lasing action. Both RL and OKE measurements indicate that
      this material is a representative of thiophene derivatives, which can be utilized
      to fabricate fast all-optical switches or random lasers (light amplifiers).

PMID- 29601134
TI  - Adsorption of 4,4'-Dithiodipyridine Axially Coordinated to Iron(II)
      Phthalocyanine on Au(111) as a New Strategy for Oxygen Reduction
      Electrocatalysis.
AB  - The coordination of PySSPy to FePc was monitored by UV/Vis spectroscopy while the
      adsobed FePc, anchored by PyS-Au(111), was examined by in situ STM in 0.1 M HClO4
      and X-ray photoelectron spectroscopy (XPS). Rotating-disc-electrode (RDE) and
      linear-sweep-voltammetry (LSV) studies on the resulting FePc-modified Au(111)
      electrodes in an oxygen-saturated 0.1 M NaOH electrolyte exhibit excellent
      electrocatalytic properties for the oxygen reduction reaction (ORR), with a
      smaller overpotential than that observed for Au(111) with FePc deposited by
      direct adsorption from a benzene solution.

PMID- 29601135
TI  - Effects of knee loading on obesity-related non-alcoholic fatty liver disease in
      an ovariectomized mouse model with high-fat diet.
AB  - AIM: Hormonal and nutritional disorders are the main causes of obesity and non
      alcoholic fatty liver disease, especially in the elderly and in postmenopausal
      women. Although physical activity might alleviate these disorders, the elderly
      may often have difficulty in carrying out physical exercise. The purpose of this
      study was to investigate the therapeutic effect of knee loading, a new form of
      physical stimulation, on the symptoms of obesity and fatty liver. METHODS: Using
      ovariectomized mice fed a high-fat diet, we evaluated the effect of knee loading
      that applies gentle cyclic loads to the knee. Female C57BL/6 mice were divided
      into five groups: control (SCD), high-fat diet (HF), HF with loading (HF + L), HF
      with ovariectomy (HF + OVX), and HF + OVX with loading (HF + OVX + L). Except for
      SCD, mice underwent sham operation or ovariectomy and were maintained on HF diet.
      After 6 weeks, the mice in the HF + L and HF + OVX + L groups were treated with
      knee loading for 6 weeks. RESULTS: Compared to the obesity groups (HF and HF +
      OVX), knee loading significantly decreased a gain in body weight, liver weight,
      and white adipose tissue (all P < 0.01). It also reduced the lipid level in the
      serum (P < 0.01) and histological severity of hepatic steatosis (P < 0.01).
      Furthermore, knee loading downregulated biomarkers related to endoplasmic
      reticulum (ER) stress (GRP78, p-eIF2alpha, and ATF4) and altered biomarkers in
      autophagy (LC3 and p62). CONCLUSIONS: Knee loading suppressed obesity-associated
      metabolic alterations and hepatic steatosis. These effects with knee loading
      might be associated with suppression of ER stress and promotion of autophagy.

PMID- 29601136
TI  - The advantage of calling things by the same name.

PMID- 29601138
TI  - Reaction Mechanism of Prephenate Dehydrogenase from the Alternative Tyrosine
      Biosynthesis Pathway in Plants.
AB  - Unlike metazoans, plants, bacteria, and fungi retain the enzymatic machinery
      necessary to synthesize the three aromatic amino acids l-phenylalanine, l
      tyrosine, and l-tryptophan de novo. In legumes, such as soybean, alfalfa, and
      common bean, prephenate dehydrogenase (PDH) catalyzes the tyrosine-insensitive
      biosynthesis of 4-hydroxyphenylpyruvate, a precursor to tyrosine. The three
      dimensional structure of soybean PDH1 was recently solved in complex with the
      NADP+ cofactor. This structure allowed for the identification of both the
      cofactor- and ligand-binding sites. Here, we present steady-state kinetic
      analysis of twenty site-directed active-site mutants of soybean (Glycine max) PDH
      compared to wild-type. Molecular docking of the substrate, prephenate, into the
      active site of the enzyme revealed its potential interactions with the active
      site residues and made a case for the importance of each residue in substrate
      recognition and/or catalysis, most likely through transition state stabilization.
      Overall, these results suggested that the active site of the enzyme is highly
      sensitive to any changes, as even subtle alterations substantially reduced the
      catalytic efficiency of the enzyme.

PMID- 29601137
TI  - Early disease progression in patients with localized natural killer/T-cell
      lymphoma treated with concurrent chemoradiotherapy.
AB  - Prognosis of patients with localized nasal extranodal natural killer/T-cell
      lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing
      treatments such as concurrent chemoradiotherapy (CCRT). However, some patients
      experience early disease progression. To clarify the clinical features and
      outcomes of these patients, data from 165 patients with localized nasal ENKL who
      were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received
      radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT
      DeVIC) were retrospectively analyzed. Progression of disease within 2 years after
      diagnosis (POD24) was used as the definition of early progression. An independent
      dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung
      Medical Center was used in the validation analysis. POD24 was documented in 23%
      of patients who received RT-DeVIC and in 25% of patients in the validation
      cohort. Overall survival (OS) from risk-defining events of the POD24 group was
      inferior to that of the reference group in both cohorts (P < .00001). In the RT
      DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2
      receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable
      Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the
      validation cohort, no pretreatment clinical factor associated with POD24 was
      identified. Our study indicates that POD24 is a strong indicator of survival in
      localized ENKL, despite the different CCRT regimens adopted. In the treatment of
      localized nasal ENKL, POD24 is useful for identifying patients who have unmet
      medical needs.

PMID- 29601139
TI  - Myocardial fibrosis evaluated by diffusion-weighted imaging and its relationship
      to 3D contractile function in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Previous studies have shown that diffusion-weighted imaging (DWI) is
      sensitive to myocardial fibrosis in ischemic and nonischemic cardiomyopathy.
      PURPOSE: To explore the prognostic value of apparent diffusion coefficient (ADC)
      for detecting myocardial fibrosis and its relationship to the contractile
      function in hypertrophic cardiomyopathy (HCM). STUDY TYPE: Prospective.
      POPULATION: A total of 45 HCM patients and 20 controls. FIELD STRENGTH/SEQUENCE:
      3.0T cardiac MRI. The cardiac MR sequences included cine, T1 mapping, and DWI.
      ASSESSMENT: According to the presence of late gadolinium enhancement (LGE) and
      the extracellular volume (ECV) values (+2 SD of control subjects), respectively,
      reader W and reader J assessed the value of ADC of each segment for detecting
      myocardial fibrosis and its relationship to impaired contractile function in HCM
      patients. STATISTICAL TESTS: Independent sample t-test, Pearson analysis, and
      intraclass correlation (ICC). RESULTS: The value of ECV was 23.6 +/- 3.0% for
      control. ECV >= 29.6% and ECV < 29.6% groups were classified. ADC values in the
      ECV >= 29.6% group were significantly increased compared to the ECV < 29.6%
      group, (2.41 +/- 0.23 MUm2 /ms vs. 2.03 +/- 0.16 MUm2 /ms, P < 0.005). Compared
      to the LGE - group, ECV (32.1 +/- 2.3% vs. 29.0 +/- 2.8%, P < 0.005) and ADC
      (2.60 +/- 0.18 MUm2 /ms vs. 2.10 +/- 0.07 MUm2 /ms, P < 0.005) values were
      significantly increased in the LGE + group. ADC values were linearly associated
      with ECV values (R2  = 0.65) in HCM patients. ADC values were linearly associated
      with circumferential and longitudinal strain (R2  = 0.60, R2  = 0.46), as well as
      circumferential, longitudinal, and radial strain rate (R2  = 0.13, R2  = 0.25, R2
      = 0.17, respectively). DATA CONCLUSION: Contractile dysfunction in HCM is
      predominantly associated with ADC, which is a feasible alternative to ECV and LGE
      for detecting myocardial fibrosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage
      2 J. Magn. Reson. Imaging 2018;48:1139-1146.

PMID- 29601140
TI  - Human serum and milk albumins are metal-dependent DNases.
AB  - It is known that that human serum albumin (HSA) and alpha-lactalbumin (LA)
      possess DNA-binding sites. Electrophoretically homogeneous HSA and LA containing
      no canonical enzymes were isolated from human sera and milk. Here we have
      analyzed for the first time the possibility of DNA hydrolysis by these proteins.
      It was shown that HSA possesses metal-dependent DNase activity, while LA cannot
      hydrolyze DNA. Several rigid criteria have been applied to show that DNase
      activity is an intrinsic property of HSA from human sera and milk. HSA
      preparations were inactive after their dialysis against EDTA or in the presence
      of EDTA, but were activated after addition of several external metal ions: Mn2+ 
      > Mg2+  > Ca2+ . The best activation of HSA preparations was observed in the
      presence of two metal ions: Mg2+ +Ca2+  > Mn2+  + Ca2+  >= Mn2+  + Mg2+ . In
      contrast to DNases having only one pH optimum, HSA preparations demonstrated two
      well-pronounced optima at pH 5.7-5.9 and 6.9-7.1 as well as a weak optimum at pH
      8.4-8.6. These results demonstrate the diversity of HSA in the DNA hydrolysis at
      various pHs and in activation by various metal cofactors. Possible reasons for
      the diversity of HSA preparations are discussed. (c) 2018 IUBMB Life, 70(6):501
      510, 2018.

PMID- 29601141
TI  - Recurrence rates of pruritus after the stop of nalfurafine hydrochloride in
      chronic liver disease: Preliminary prospective confirmatory trial.
AB  - AIM: The recurrence rates of pruritus after stopping nalfurafine hydrochloride
      are unknown in chronic liver disease. METHODS: A prospective confirmatory trial
      was carried out to determine the recurrence rates of pruritus after cessation of
      nalfurafine hydrochloride in chronic liver disease. After pretreatment with
      nalfurafine hydrochloride for 4 weeks or more, 15 consecutive Japanese patients,
      who confirmed the improvement of pruritus (decrease in the visual analogue scale
      (VAS) of >=50 mm), were enrolled in the present study. Patients were classified
      to the continuous group (continuation of nalfurafine hydrochloride for 4 weeks)
      or the discontinuous group (cessation of nalfurafine hydrochloride) at the time
      of consent to study protocol, by self-determination. RESULTS: The recurrence
      rates (increase in VAS of >=25 mm after stopping nalfurafine hydrochloride) were
      100% (5 of 5 patients) and 0% (0 of 10) in the discontinuous and continuous
      groups, respectively. In the discontinuous group, 3 patients selected retreatment
      with nalfurafine hydrochloride as salvage therapy, and they generally recovered
      to the levels of VAS at the discontinuation of treatment. CONCLUSION: The present
      prospective trial showed the high recurrence rates of pruritus after the stop of
      nalfurafine hydrochloride in chronic liver disease.

PMID- 29601142
TI  - Relocating cued goals induces population remapping in CA1 related to memory
      performance in a two-platform water task in rats.
AB  - The activity of CA1 neurons in the rodent hippocampus represents multiple aspects
      of learning episodes, including cue and place information. Previous reports on
      cue and place representation in CA1 have examined activity in single neurons and
      population recordings during free exploration of an environment or when actions
      are directed to either cue or place aspects of memory tasks. To better understand
      cue and place memory representation in CA1, and how these interact during goal
      directed navigation, we investigated population activity in CA1 during memory
      encoding and retrieval in a novel water task with two visibly distinct platforms,
      using mRNA for immediate early genes Arc and Homer1a as markers of neural
      activity. After training, relocating cues to new places induces an extensive,
      perhaps global, remapping of the memory code that is accompanied by altered
      navigation and rapid learning of new cue-place information. In addition, we have
      found a significant relationship between the extent of reactivation and overall
      cue choice accuracy. These findings demonstrate an important relationship between
      population remapping in CA1 and memory-guided behavior.

PMID- 29601144
TI  - oneED: Embedding a mindfulness-based wellness programme into an emergency
      department.
AB  - OBJECTIVE: ED staff are subject to many stressors, but there are few descriptions
      of collective approaches to enhancing wellness in this setting. We aim to
      describe a programme developed to address these issues at department level, to
      report the feasibility and sustainability of the programme, and its impact on
      staff. METHODS: The oneED programme was developed and delivered in a tertiary ED.
      The programme included a 1 day mindfulness workshop, followed by ongoing
      mindfulness activities embedded in clinical areas over the subsequent 12 months.
      A mixed-methods evaluation of the programme was conducted, which included
      quantitative validated psychological tools to measure anxiety, depression and
      emotional exhaustion, and pragmatic evaluation using surveys of participants and
      iterative appreciative inquiry. RESULTS: Eighty staff members attended the
      mindfulness workshop; 66 from ED. Following the workshop, understanding and
      frequency of mindfulness practice increased significantly in 47% of participants.
      Free-text survey results demonstrated that staff found the programme to be
      acceptable (80% survey participants) and of perceived value to themselves (50%)
      and the ED (60%). Appreciative inquiry led to modification of the programme: the
      4 min pause is now conducted weekly rather than daily, the pause consists of a
      variety of activities, and group activities are made more overtly optional.
      CONCLUSION: A departmental wellness programme embedding mindfulness practice is
      feasible and sustainable. Potential for success is enhanced by an approach that
      is open to modification according to each institution's culture.

PMID- 29601143
TI  - Synthetic alpha-mangostin dilaurate strongly suppresses wide-spectrum organ
      metastasis in a mouse model of mammary cancer.
AB  - We previously reported that, in a mouse model of mammary cancer, alpha-mangostin
      alone exhibits anti-metastatic properties. To enhance this anti-metastatic
      effect, we examined the efficacy of synthetic alpha-mangostin dilaurate (MGD),
      prepared by adding lauric acid to alpha-mangostin, in the same experimental
      system wherein mice bearing mammary tumors are exposed to dietary MGD at 0, 2000
      and 4000 ppm. Lauric acid has a high propensity for lymphatic absorption, which
      is the most common pathway of initial dissemination of many solid malignancies.
      Both mammary tumor volumes and wide-spectrum organ metastasis were markedly
      reduced at 2000 and 4000 ppm: furthermore, survival in the 4000-ppm group was
      significantly greater than in control mice. Apoptosis in mammary carcinomas was
      also significantly increased in the 4000-ppm group, whereas blood microvessel
      density and lymphatic vessel invasion were markedly reduced. In real-time PCR
      analyses of tumor samples, increased p21 and decreased Pcna expression were
      observed with 4000 ppm but values were not statistically significant when
      compared to expression in control tumors. However, exposure to 4000 ppm
      significantly decreased expression of phospho-Akt (Ser473/Thr308) as compared to
      the control, indicating a role in the anti-tumorigenic effects of MGD. These
      findings suggest that MGD may be useful for adjuvant therapy and chemoprevention
      and that conjugated medium-chain fatty acids may enhance the efficacy of certain
      chemotherapeutic agents.

PMID- 29601145
TI  - Comparative efficacy and safety of low-intensity warfarin therapy in preventing
      unprovoked recurrent venous thromboembolism: A systematic review and meta
      analysis.
AB  - BACKGROUND: Although there exists potential risk of bleeding, extended 'lifelong'
      conventional-intensity [international normalized ratio (INR): 2.0-3.0] warfarin
      anticoagulation is recommended for unprovoked venous thromboembolism (VTE)
      patients because of risk of recurrent VTE. Whether long-term low-intensity (INR:
      1.5-2.0) warfarin therapy reduced the risk of major bleeding without
      substantially lowered antithrombotic efficacy is not well understood. The aim of
      this study was to perform a systematic review and meta-analysis to evaluate the
      risk-benefits of low-intensity warfarin therapy. METHODS: We conducted a
      comprehensive search of electronic databases and included randomized control
      trials (RCTs) that reported efficacy (recurrent VTE) and safety (bleeding
      episodes) of low-intensity warfarin therapy compared with conventional-intensity
      warfarin or placebo from inception through Jun 2016. RESULTS: Four RCTs reporting
      high GRADE quality evidence were included. Although the relative risk of
      recurrent VTE with low-intensity therapy was significantly increased [2.96 (95%
      CI: 1.40 to 6.24), P < .004] compared to conventional-intensity warfarin, there
      was significant decrease of relative risk when compared with placebo [0.37 (95%
      CI: 0.24 to 0.56), P < .00001]. As per included publications, no significant
      major bleeding episodes were observed in low-intensity warfarin group.
      CONCLUSIONS: Although less effective than conventional-intensity warfarin therapy
      this meta-analysis indicates that long-term low-intensity warfarin therapy is
      highly effective for preventing recurrent VTE than placebo, along with reduced
      risks of major bleeding and minimizing potential complications.

PMID- 29601147
TI  - Supervised physical exercise improves clinical, anthropometric and biochemical
      parameters in adult cystic fibrosis patients: A 2-year evaluation.
AB  - OBJECTIVE: Cystic fibrosis (CF) is the most common inherited, life limiting
      condition among Caucasians. No healing therapy is currently available for
      patients with CF. The aim of the study was to define clinical, anthropometric and
      biochemical effects of regular, supervised physical exercise in a large cohort of
      patients with CF. MATERIALS AND METHODS: Fifty-nine adult patients with CF that
      performed regularly supervised physical exercise in the last 3 years in
      comparison to 59 sex and age matched sedentary patients with CF were included in
      the study. RESULTS: Physical exercise had significantly beneficial effects on:
      (a) FEV1% decline; (b) anthropometric parameters (lower number of cases with
      altered BMI, waist and arm circumferences); (c) lipid and glucose metabolism; (d)
      vitamin D serum levels. Of course, some of this improvement may be because of the
      better adherence to therapy typical of patients with CF that perform physical
      activity. CONCLUSIONS: Such clinical and metabolic effects make supervised
      physical activity one of the hubs in managing patients with CF.

PMID- 29601148
TI  - Maintenance of Continuity in Older Adulthood: Concept Analysis.
AB  - PURPOSE: This article aims to define the concept of maintenance of continuity in
      older adulthood (MCOA) and assist nurses to better understand the concept of
      MCOA. METHODS: The method by Walker and Avant was used for this concept analysis.
      FINDINGS: In the literature, MCOA is defined as a psychosocial adaptation
      strategy by searching for preference and familiarity, making a sense of
      connection, and creating coherence. CONCLUSIONS: MCOA has potential to improve
      psychosocial adjustment to difficult life transitions as a coping mechanism.
      IMPLICATION FOR NURSING PRACTICE: Insights about MCOA in nursing may contribute
      to improved patient care outcomes by assisting nurses to understand the elderly's
      experience during age-related challenges from a life course perspective.

PMID- 29601146
TI  - Quantification of near-wall hemodynamic risk factors in large-scale cerebral
      arterial trees.
AB  - Detailed hemodynamic analysis of blood flow in pathological segments close to
      aneurysm and stenosis has provided physicians with invaluable information about
      the local flow patterns leading to vascular disease. However, these diseases have
      both local and global effects on the circulation of the blood within the cerebral
      tree. The aim of this paper is to demonstrate the importance of extending subject
      specific hemodynamic simulations to the entire cerebral arterial tree with
      hundreds of bifurcations and vessels, as well as evaluate hemodynamic risk
      factors and waveform shape characteristics throughout the cerebral arterial
      trees. Angioarchitecture and in vivo blood flow measurement were acquired from
      healthy subjects and in cases with symptomatic intracranial aneurysm and
      stenosis. A global map of cerebral arterial blood flow distribution revealed
      regions of low to high hemodynamic risk that may significantly contribute to the
      development of intracranial aneurysms or atherosclerosis. Comparison of pre
      intervention and post-intervention of pathological cases further shows large
      angular phase shift (~33.8 degrees ), and an augmentation of the peak-diastolic
      velocity. Hemodynamic indexes of waveform analysis revealed on average a 16.35%
      reduction in the pulsatility index after treatment from lesion site to downstream
      distal vessels. The lesion regions not only affect blood flow streamlines of the
      proximal sites but also generate pulse wave shift and disturbed flow in
      downstream vessels. This network effect necessitates the use of large-scale
      simulation to visualize both local and global effects of pathological lesions.

PMID- 29601149
TI  - Colorectal carcinoma: Ex vivo evaluation using q-space imaging; Correlation with
      histopathologic findings.
AB  - BACKGROUND: Although the prognosis of colorectal carcinoma (CRC) patients depends
      on the histologic grade (HG) and lymph node metastasis (LNM), accurate
      preoperative assessment of these prognostic factors is often difficult. PURPOSE:
      To assess the HG and extent of LNM by q-space imaging (QSI) for preoperative
      diagnosis of CRC. STUDY TYPE: Prospective. SPECIMEN: A total of 20 colorectal
      tissue samples containing adenocarcinomas and resected lymph nodes (LNs). FIELD
      STRENGTH/SEQUENCE: QSI was performed with a 3T MRI system using a diffusion
      weighted echo-planar imaging sequence: repetition time, 10,000 msec; echo time,
      216 or 210 msec; field of view, 113 * 73.45 mm; matrix, 120 * 78; section
      thickness, 4 mm; and 11 b values ranging from 0 to 9000 s/mm2 . ASSESSMENT: The
      mean displacement (MDP; MUm), zero-displacement probability (ZDP; arbitrary unit
      [a.u.]), kurtosis (K; a.u.), and apparent diffusion coefficient (ADC) were
      analyzed by two observers and compared with histopathologic findings. STATISTICAL
      TESTS: Spearman's rank correlation coefficient, Mann-Whitney U-test, and ROC
      curve analyses. RESULTS: For all 20 carcinomas, the MDP, ZDP, K, and ADC were
      8.87 +/- 0.37 MUm, 82.0 +/- 6.2 a.u., 74.3 +/- 3.0 a.u., and 0.219 +/- 0.040 * 10
      3 mm2 /s, respectively. The MDP (r = -0.768; P < 0.001), ZDP (r = 0.768; P <
      0.001), and K (r = 0.785; P < 0.001) were significantly correlated with the HG of
      CRC, but not the ADC (r = 0.088; P = 0.712). There were also significant
      differences in the MDP, ZDP, and K between metastatic and nonmetastatic LNs (all,
      P < 0.001), but not the ADC (P = 0.082). In the HG of CRC and LNM, the area under
      the curve was significantly greater for MDP, ZDP, and K than for ADC. DATA
      CONCLUSION: QSI provides useful diagnostic information to assess the HG and
      extent of LNM in CRC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn.
      Reson. Imaging 2018;48:1059-1068.

PMID- 29601151
TI  - Combined DFT and Differential Electrochemical Mass Spectrometry Investigation of
      the Effect of Dopants in Secondary Zinc-Air Batteries.
AB  - Zinc-air batteries offer the potential of low-cost energy storage with high
      specific energy, but at present secondary Zn-air batteries suffer from poor
      cyclability. To develop economically viable secondary Zn-air batteries, several
      properties need to be improved: choking of the cathode, catalyzing the oxygen
      evolution and reduction reactions, limiting dendrite formation and suppressing
      the hydrogen evolution reaction (HER). Understanding and alleviating HER at the
      negative electrode in a secondary Zn-air battery is a substantial challenge, for
      which it is necessary to combine computational and experimental research. Here,
      we combine differential electrochemical mass spectrometry (DEMS) and density
      functional theory (DFT) calculations to investigate the fundamental role and
      stability when cycling in the presence of selected beneficial additives, that is,
      In and Bi, and Ag as a potentially unfavorable additive. We show that both In and
      Bi have the desired property for a secondary battery, that is, upon recharging
      they will remain on the surface, thereby retaining the beneficial effects on Zn
      dissolution and suppression of HER. This is confirmed by DEMS, where it is
      observed that In reduces HER and Bi affects the discharge potential beneficially
      compared to a battery without additives. Using a simple procedure based on
      adsorption energies calculated with DFT, it is found that Ag suppresses OH
      adsorption, but, unlike In and Bi, it does not hinder HER. Finally, it is shown
      that mixing In and Bi is beneficial compared to the additives by themselves as it
      improves the electrochemical performance and cyclic stability of the secondary Zn
      air battery.

PMID- 29601150
TI  - Comparing the efficacy of Silastic and gloved-Merocel middle meatal spacers for
      functional endoscopic sinus surgery: a randomized controlled trial.
AB  - BACKGROUND: Spacers are inserted into the middle meatal space (MMS) following
      functional endoscopic sinus surgery (FESS) to prevent lateralization of the
      middle turbinate, scarring, and synechiae. Our objective was to determine if the
      incidence of postoperative synechiae, facial pain/discomfort, pain during spacer
      removal, scarring, and discharge differed between nasal cavities receiving
      Silastic or gloved-Merocel (GM) spacers following FESS. METHODS: A double-blind,
      randomized controlled trial (RCT) was conducted in adults requiring bilateral
      FESS for chronic rhinosinusitis (CRS) +/- nasal polyposis. Participants served as
      their own controls, with each subject receiving both a Silastic and GM spacer.
      Spacers were inserted into the MMS during FESS and left in situ for 6 days.
      Participants were reviewed at 6 days, 5 weeks, and 12 weeks postoperatively. The
      presence of synechiae and scarring were evaluated endoscopically. Inflammation,
      discharge, and pain during spacer removal were assessed using a visual analogue
      scale (VAS). RESULTS: Forty-eight participants (96 nasal cavities) were
      recruited. Preoperatively, Lund-Mackay computed tomography (CT) scores were
      similar between Silastic-treated and GM-treated cavities (6.38 +/- 2.35 vs 6.18
      +/- 2.17). The incidence of synechiae and scarring did not differ significantly
      between spacers up to 12 weeks postoperatively. Pain during spacer removal was
      significantly greater for Silastic than GM spacers (2.13 +/- 1.34 vs 1.51 +/-
      1.23, p = 0.020). Facial pain prior to removal and extent of discharge did not
      differ significantly between spacers. CONCLUSION: Following FESS, patients report
      less pain during removal of GM than Silastic spacers. However, the likelihood of
      synechiae and scarring did not differ between either of the spacers.

PMID- 29601152
TI  - Combat zone exposure and respiratory tract disease.
AB  - BACKGROUND: The impact of deployment to combat zones on the respiratory and
      sinonasal health of U.S. soldiers is an emerging public health concern.
      Retrospective studies have shown a correlation between deployment and development
      of post-deployment pathology, particularly of the aerodigestive system.
      Respiratory disease, including sinusitis, allergic rhinitis, and asthma, are
      commonly reported in soldiers deployed to the Middle East and Southwest Asia.
      METHODS: Current literature pertaining to combat zone exposure and development of
      respiratory disease was retrieved using PubMed, Embase, Web of Science, and
      Google Scholar. RESULTS: Several types of combat zone exposures exist that may
      play an influential role in the development of upper and lower respiratory tract
      diseases. Exposures including foreign dusts, harsh environments, particulate
      size, and close living quarters may play a causative role. The effect of combat
      zone exposures has been better examined for lower respiratory tract diseases;
      however, with the theory of the unified airway, the upper respiratory tract may
      also be involved. There is evidence that the upper respiratory tract is
      susceptible, with an increased risk for development of sinusitis and sinonasal
      disease; however, the quality of evidence of the present literature is generally
      low. CONCLUSION: More research is necessary to determine a pathophysiologic
      mechanism between combat zone exposure and the development of sinonasal disease.
      Practicing otolaryngologists should be aware of the possibility of combat zone
      exposures that could contribute to rhinologic symptomatology.

PMID- 29601153
TI  - Lacrimal sac exposure and a superior lateral anterior pedicle flap to improve
      outcomes of Draf type II and III procedures.
AB  - BACKGROUND: Although the efficacy of Draf type II and III procedures for frontal
      sinus diseases is well recognized, a certain amount of postoperative stenosis of
      the frontal neo-ostium occurs. Exposed bone induces inflammation and leads to
      osteoneogenesis. To prevent stenosis, we developed a surgical technique designed
      to minimize bone exposure while maximizing the frontal neo-ostium area created
      with Draf type II and III procedures. We fully exposed the lacrimal sac and used
      a superior lateral anterior pedicle flap to cover the exposed bone during the
      Draf procedure. We aimed to describe our technique. METHODS: We reviewed 19
      patients who underwent a Draf type II or III procedure with our technique.
      Endoscopic views from the follow-ups and complications were evaluated. RESULTS:
      Overall, the neo-ostium remained patent in all patients. No complications, such
      as synechiae or orbital injury, were seen in any of the patients. CONCLUSION:
      Draf type II and III procedures with lacrimal sac exposure and a superior lateral
      anterior pedicle flap are convenient and seem to be effective. However, further
      studies with larger numbers of patients are needed to verify our technique.

PMID- 29601154
TI  - Intentional Inconsistency as Gender-Neutral Language Evolves.

PMID- 29601156
TI  - An Update on Menopause Management (2018/016).

PMID- 29601155
TI  - Sexual Health and Sexual Problems.

PMID- 29601157
TI  - Measure First, then Manage.
AB  - The transition into the new health care environment born of value-based
      purchasing and managed care  may be stormy, but proactive providers that can
      produce data proving their quality will emerge leaner and more efficient.

PMID- 29601158
TI  - What Caregivers Need To Know About Aging Eyes.
AB  - Exams for early detection of diseases afflicting the eyes are imperative to
      reducing unnecessary vision loss.

PMID- 29601159
TI  - Practical Vision: Telescope Implants Score Large.
AB  - Some assisted living or skilled nursing residents with macular degeneration may
      be eligible for a surgical procedure that could turn their lives around.

PMID- 29601160
TI  - Leveraging Data Can Help Accelerate Change.
AB  - Waiting for CMS to report and rate a Center based on its MDS submissions
      eliminates the opportunity to make point-of-care changes.

PMID- 29601161
TI  - From Tundra To Table.

PMID- 29601162
TI  - Poised to Take the New Payment Leap.
AB  - While some providers are collaborating with hospitals to join networks, others
      have been hesitant.

PMID- 29601163
TI  - Medication Reconciliation Makes Transitions Safer.
AB  - A thoughtfully designed and strictly followed review process can spare patients
      avoidable hospital readmissions.

PMID- 29601164
TI  - Electronic Coordination Key To Better Care.
AB  - Unlike hospitals, LTPAC is delivered in widely scattered settings, which makes
      coordinating caregiver efforts extremely challenging.

PMID- 29601165
TI  - Policies Should Reflect The Changing Law Landscape.
AB  - EEOC has Ruled that discrimination based on sexual orientation is simply another
      form of sex discrimination.

PMID- 29601166
TI  - Advance Directives: Making The Tough Choices.
AB  - It's hard for patients, family members, and clinicians to talk about a possible
      catastrophic event, but it could forestall added anxiety down the road.

PMID- 29601167
TI  - Banks Cater To Long Term Care.
AB  - Providers are looking for money to invest in their businesses both for the short
      and long term.

PMID- 29601168
TI  - More Than Just Pretty Pictures.
AB  - Data visualization can help staff members, from certified nurse assistants to
      executives, comprehend the data they need to do their jobs.

PMID- 29601169
TI  - Investment Capital Needed For Skilled Nursing Operations.
AB  - Providers may attract more investors for their operations if they pool and
      aggregate their current data to show current trends.

PMID- 29601170
TI  - Web Strategies Can Bring In Customers.
AB  - Providers can flip their websites from liabilities into assets and capture and
      close their own referrals.

PMID- 29601171
TI  - The Accelerated Pace Of The Short-Stay Patient.
AB  - Everything moves faster in the rehab arena, from the time it takes to get to know
      patients, to the time it takes to get them ready to go home.

PMID- 29601172
TI  - Online Courses Open Learning Opportunities.
AB  - Training programs on the internet have become a convenient and popular resource
      for providers and their staff members.

PMID- 29601173
TI  - Langmuir-Blodgett Thin Films of Diketopyrrolopyrrole-Based Amphiphiles.
AB  - We report on two pi-conjugated donor-acceptor-donor (D-A-D) molecules of
      amphiphilic nature, aiming to promote intermolecular ordering and carrier
      mobility in organic electronic devices. Diketopyrrolopyrrole was selected as the
      acceptor moiety that was disubstituted with nonpolar and polar functional groups,
      thereby providing the amphiphilic structures. This structural design resulted in
      materials with a strong intermolecular order in the solid state, which was
      confirmed by differential scanning calorimetry and polarized optical microscopy.
      Langmuir-Blodgett (LB) films of ordered mono- and multilayers were transferred
      onto glass and silicon substrates, with layer quality, coverage, and
      intermolecular order controlled by layer compression pressure on the LB trough.
      Organic field-effect transistors and organic photovoltaics devices with active
      layers consisting of the amphiphilic conjugated D-A-D-type molecules were
      constructed to demonstrate that the LB technique is an effective layer-by-layer
      deposition approach to fabricate self-assembled, ordered thin films.

PMID- 29601174
TI  - Correction to One-Pot Synthesis of Superfine Core-Shell Cu@metal Nanowires for
      Highly Tenacious Transparent LED Dimmer.

PMID- 29601175
TI  - Interfacial Energy-Level Alignment for High-Performance All-Inorganic Perovskite
      CsPbBr3 Quantum Dot-Based Inverted Light-Emitting Diodes.
AB  - All-inorganic perovskite light-emitting diode (PeLED) has a high stability in
      ambient atmosphere, but it is a big challenge to achieve high performance of the
      device. Basically, device design, control of energy-level alignment, and reducing
      the energy barrier between adjacent layers in the architecture of PeLED are
      important factors to achieve high efficiency. In this study, we report a CsPbBr3
      based PeLED with an inverted architecture using lithium-doped TiO2 nanoparticles
      as the electron transport layer (ETL). The optimal lithium doping balances the
      charge carrier injection between the hole transport layer and ETL, leading to
      superior device performance. The device exhibits a current efficiency of 3 cd A
      1, a luminance efficiency of 2210 cd m-2, and a low turn-on voltage of 2.3 V. The
      turn-on voltage is one of the lowest values among reported CsPbBr3-based PeLEDs.
      A 7-fold increase in device efficiencies has been obtained for lithium-doped TiO2
      compared to that for undoped TiO2-based devices.

PMID- 29601176
TI  - Potent 1,2,4-Triazino[5,6 b]indole-3-thioether Inhibitors of the Kanamycin
      Resistance Enzyme Eis from Mycobacterium tuberculosis.
AB  - A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression
      of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase
      that multiacetylates KAN and other aminoglycosides, rendering them unable to bind
      the bacterial ribosome. By high-throughput screening, a series of substituted
      1,2,4-triazino[5,6 b]indole-3-thioether molecules were identified as effective
      Eis inhibitors. Herein, we purchased 17 and synthesized 22 new compounds,
      evaluated their potency, and characterized their steady-state kinetics. Four
      inhibitors were found not only to inhibit Eis in vitro, but also to act as
      adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium
      tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal
      structure of Eis in complex with a potent inhibitor and CoA shows that the
      inhibitors bind in the aminoglycoside binding site snugly inserted into a
      hydrophobic cavity. These inhibitors will undergo preclinical development as
      novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.

PMID- 29601177
TI  - Pulsed Hydrogen-Deuterium Exchange Illuminates the Aggregation Kinetics of alpha
      Synuclein, the Causative Agent for Parkinson's Disease.
AB  - alpha-Synuclein (aS) forms toxic intermediates ranging from small oligomers and
      protofibrils to large amyloid fibrils. Understanding the time course of aS fibril
      formation and the role played by its regions is critical for therapeutic
      intervention. Here, we used pulsed hydrogen-deuterium exchange and mass
      spectrometry (HDX-MS) for the first time to probe kinetic intermediates of the
      full aS aggregation in vitro, achieving kinetic snapshots containing spatially
      resolved protein information about critical stages. Monitoring the resultant mass
      shifts shows distinct binomial abundances for two main exchange profiles: one
      that represents a fast-exchanging, solvent-accessible species and another with a
      more protected nature. We show using a series of proteolytic peptides from the
      full protein that self-association is most pronounced in the non-amyloid-beta
      component region and less so for either terminus. The N-terminus, however, shows
      a minor protected population at mid- and late times, whereas the C-terminus shows
      predominantly unimodal HDX, indicating that these regions are devoid of any large
      conformational rearrangements. Focusing on the hydrophobic core, we confirmed and
      modeled the different isotopic distributions and calculated their relative
      fractions to discern their individual contributions. The data fitting reports
      respective t1/2 values, which are nearly identical and do not depend on location.
      We followed the aggregation by complementary transmission electron microscopy to
      observe the morphology of aggregates and circular dichroism to assess changes in
      secondary structure. Our results provide a detailed picture of aS aggregation in
      vitro and demonstrate that HDX-MS offers unique spatially resolved, coexisting
      kinetic intermediates in solution. This new platform is suitable for testing
      promising inhibitors of aS aggregation.

PMID- 29601178
TI  - Enhanced Osteogenic Differentiation of Stem Cells on Phase-Engineered Graphene
      Oxide.
AB  - Graphene oxide (GO) has attracted significant interest as a template material for
      multiple applications due to its two-dimensional nature and established
      functionalization chemistries. However, for applications toward stem cell culture
      and differentiation, GO is often reduced to form reduced graphene oxide,
      resulting in a loss of oxygen content. Here, we induce a phase transformation in
      GO and demonstrate its benefits for enhanced stem cell culture and
      differentiation while conserving the oxygen content. The transformation results
      in the clustering of oxygen atoms on the GO surface, which greatly improves its
      ability toward substance adherence and results in enhanced differentiation of
      human mesenchymal stem cells toward the osteogenic lineage. Moreover, the
      conjugating ability of modified GO strengthened, which was examined by auxiliary
      osteogenic growth peptide conjugation. Overall, our work demonstrates GO's
      potential for stem cell applications while maintaining its oxygen content, which
      could enable further functionalization and fabrication of novel nano
      biointerfaces.

PMID- 29601179
TI  - Enhancing Electrochemical Performance of Graphene Fiber-Based Supercapacitors by
      Plasma Treatment.
AB  - Graphene fiber-based supercapacitors (GFSCs) hold high power density, fast charge
      discharge rate, ultralong cycling life, exceptional mechanical/electrical
      properties, and safe operation conditions, making them very promising to power
      small wearable electronics. However, the electrochemical performance is still
      limited by the severe stacking of graphene sheets, hydrophobicity of graphene
      fibers, and complex preparation process. In this work, we develop a facile but
      robust strategy to easily enhance electrochemical properties of all-solid-state
      GFSCs by simple plasma treatment. We find that 1 min plasma treatment under an
      ambient condition results in 33.1% enhancement of areal specific capacitance
      (36.25 mF/cm2) in comparison to the as-prepared GFSC. The energy density reaches
      0.80 MUW h/cm2 in polyvinyl alcohol/H2SO4 gel electrolyte and 18.12 MUW h/cm2 in
      poly(vinylidene difluoride)/ethyl-3-methylimidazolium tetrafluoroborate
      electrolyte, which are 22 times of that of as-prepared ones. The plasma-treated
      GFSCs also exhibit ultrahigh rate capability (69.13% for 40 s plasma-treated
      ones) and superior cycle stability (96.14% capacitance retention after 20 000
      cycles for 1 min plasma-treated ones). This plasma strategy can be extended to
      mass-manufacture high-performance carbonaceous fiber-based supercapacitors, such
      as graphene and carbon nanotube-based ones.

PMID- 29601180
TI  - Filament Growth and Resistive Switching in Hafnium Oxide Memristive Devices.
AB  - We report on the resistive switching in TiN/Ti/HfO2/TiN memristive devices. A
      resistive switching model for the device is proposed, taking into account
      important experimental and theoretical findings. The proposed switching model is
      validated using 2D and 3D kinetic Monte Carlo simulation models. The models are
      consistently coupled to the electric field and different current transport
      mechanisms such as direct tunneling, trap-assisted tunneling, ohmic transport,
      and transport through a quantum point contact have been considered. We find that
      the numerical results are in excellent agreement with experimentally obtained
      data. Important device parameters, which are difficult or impossible to measure
      in experiments, are calculated. This includes the shape of the conductive
      filament, width of filament constriction, current density, and temperature
      distribution. To obtain insights in the operation of the device, consecutive
      cycles have been simulated. Furthermore, the switching kinetics for the forming
      and set process for different applied voltages is investigated. Finally, the
      influence of an annealing process on the filament growth, especially on the
      filament growth direction, is discussed.

PMID- 29601181
TI  - Innovative Ti1- xNb xN-Ag Films Inducing Bacterial Disinfection by Visible
      Light/Thermal Treatment.
AB  - This study presents innovative Ti1- xNb xN-Ag films obtained by a suitable
      combination of low-energy and high-energy sputtering leading to bacterial
      inactivation. The bacterial inactivation kinetics by the TiNbN layers was
      drastically enhanced by the addition of 6-7% Ag and proceeded to completion
      within 3 h after the film autoclaving. By X-ray photoelectron spectroscopy (XPS),
      the samples after autoclaving presented in their upper layers TiO2, Nb2O5 and
      Ag2O with a surface composition of Ti0.81Nb0.19N0.99Ag0.068. Surface potential/pH
      changes in the Ti1- xNb xN-Ag films were monitored during bacterial inactivation.
      Surface redox processes during the bacterial inactivation were detected by XPS.
      The diffusion of Ag in the Ti1- xNb xN-Ag films was followed at 50 and 70 
      degrees C pointing. The beneficial thermal treatment points out to the
      bifunctional bacterial inactivation properties of these films and their potential
      application in healthcare facilities. Interfacial charge transfer (IFCT) under
      light irradiation between Ag2O, Nb2O5 and TiO2 is suggested consistent with the
      data found during the course of this study. The TiO2/Nb2O5 lattice mechanism is
      discussed in the framework of the Verwey's controlled valence model. The surface
      properties of the Ti1- xNb xN-Ag films were investigated by X-ray diffraction,
      atomic force microscopy, and scanning electron microscopy.

PMID- 29601182
TI  - Sniffing Entrapped Humans with Sensor Arrays.
AB  - Earthquakes are lethal natural disasters frequently burying people alive under
      collapsed buildings. Tracking entrapped humans from their unique volatile
      chemical signature with hand-held devices would accelerate urban search and
      rescue (USaR) efforts. Here, a pilot study is presented with compact and
      orthogonal sensor arrays to detect the breath- and skin-emitted metabolic tracers
      acetone, ammonia, isoprene, CO2, and relative humidity (RH), all together serving
      as sign of life. It consists of three nanostructured metal-oxide sensors (Si
      doped WO3, Si-doped MoO3, and Ti-doped ZnO), each specifically tailored at the
      nanoscale for highly sensitive and selective tracer detection along with
      commercial CO2 and humidity sensors. When tested on humans enclosed in
      plethysmography chambers to simulate entrapment, this sensor array rapidly
      detected sub-ppm acetone, ammonia, and isoprene concentrations with high
      accuracies (19, 21, and 3 ppb, respectively) and precision, unprecedented by
      portable sensors but required for USaR. These results were in good agreement
      (Pearson's correlation coefficients >=0.9) with benchtop selective reagent
      ionization time-of-flight mass spectrometry (SRI-TOF-MS). As a result, an
      inexpensive sensor array is presented that can be integrated readily into hand
      held or even drone-carried detectors for first responders to rapidly screen
      affected terrain.

PMID- 29601183
TI  - Specifically and Visually Detect Methyl-Mercury and Ethyl-Mercury in Fish Sample
      Based on DNA-Templated Alloy Ag-Au Nanoparticles.
AB  - Methyl-mercury (CH3Hg+) and ethyl-mercury (C2H5Hg+) have much higher toxicity
      than Hg2+ and can be more easily accumulated by organisms to form severe
      bioamplification. Hence, the specific and on-site detection of CH3Hg+ and C2H5Hg+
      in seafood is of great significance and a hard challenge. We herein designed two
      T-rich aptamers (HT5 and HT7) for specifically recognizing CH3Hg+ and the total
      of CH3Hg+ and C2H5Hg+, respectively. In the presence of all Au3+, Ag+, and T-rich
      aptamer, CH3Hg+ and C2H5Hg+ specifically and preferentially bind with aptamer and
      thus induced the formation of alloy Ag-Au nanoparticles after reduction, which
      led to the color change in solution. This provided a sensing platform for the
      instrument-free visual discrimination and detection of CH3Hg+ and C2H5Hg+. By
      using HT5 as probe, the method can be used to detect as low as 5.0 MUM
      (equivalent to 1.0 MUg Hg/g) of CH3Hg+ by bare eye observation and 0.5 MUM
      (equivalent to 100 ng Hg/g) of CH3Hg+ by UV-visible spectrometry. By using HT7 as
      probe, the method can be used to detect the total concentration of CH3Hg+ and
      C2H5Hg+ with a visual detection limit of 5.0 MUM (equivalent to 1.0 MUg Hg/g) and
      a UV-visible spectrometry detection limit of 0.6 MUM (equivalent to 120 ng Hg/g).
      The proposed method has been successfully used to detect CH3Hg+ and C2H5Hg+ in
      fish muscle samples with a recovery of 101-109% and a RSD ( n = 6) < 8%. The
      success of this study provided a potential method for the specific and on-site
      detection of CH3Hg+ and C2H5Hg+ in seafood by only bare eye observation.

PMID- 29601184
TI  - Exploring Conditions for Ultrafine Particle Formation from Oxidation of Cigarette
      Smoke in Indoor Environments.
AB  - Cigarette smoke is an important source of particles and gases in the indoor
      environment. In this work, aging of side-stream cigarette smoke was studied in an
      environmental chamber via exposure to ozone (O3), hydroxyl radicals (OH) and
      indoor fluorescent lights. Aerosol mass concentrations increased by 13-18% upon
      exposure to 15 ppb O3 and by 8-42% upon exposure to 0.45 ppt OH. Ultrafine
      particle (UFP) formation was observed during all ozone experiments, regardless of
      the primary smoke aerosol concentration (185-1950 MUg m-3). During OH oxidation,
      however, UFP formed only when the primary particle concentration was relatively
      low (<130 MUg m-3) and the OH concentration was high (~1.1 * 107 molecules cm-3).
      Online aerosol composition measurements show that oxygen- and nitrogen-
      containing species were formed during oxidation. Gas phase oxidation of NO to NO2
      occurred during fluorescent light exposure, but neither primary particle growth
      nor UFP formation were observed. Overall, exposure of cigarette smoke to ozone
      will likely lead to UFP formation in indoor environments. On the other hand, UPF
      formation via OH oxidation will only occur when OH concentrations are high (~107
      molecules cm-3), and is therefore less likely to have an impact on indoor aerosol
      associated with cigarette smoke.

PMID- 29601185
TI  - Lead Diversification at the Nanomole Scale Using Liver Microsomes and
      Quantitative Nuclear Magnetic Resonance Spectroscopy: Application to
      Phosphodiesterase 2 Inhibitors.
AB  - In this report, we describe a method whereby lead molecules can be converted into
      several new analogues each using liver microsomes. Less than one micromole of
      substrate is incubated with liver microsomes (mouse, rat, hamster, guinea pig,
      rabbit, dog, monkey, or human) to produce multiple products which are isolated
      and analyzed by quantitative cryomicroprobe NMR (qNMR) spectroscopy. The
      solutions from qNMR analysis were then used as stocks that were diluted into
      biochemical assays. Nine human phosphodiesterase-2 (PDE2) inhibitors yielded 36
      new analogues. Products were tested for PDE2 inhibition, intrinsic clearance in
      human hepatocytes, and membrane permeability. Two of the products (2c and 4b)
      were 3-10* more potent than their respective parent compounds and also had
      improved metabolic stability. Others offered insights into structure-activity
      relationships. Overall, this process of using liver microsomes at a submicromole
      scale of substrate is a useful approach to rapid and cost-effective late-stage
      lead diversification.

PMID- 29601186
TI  - Periodic Density Functional Theory Study of the Structure, Raman Spectrum, and
      Mechanical Properties of Schoepite Mineral.
AB  - The structure and Raman spectrum of schoepite mineral, [(UO2)8O2(OH)12].12H2O,
      was studied by means of theoretical calculations. The computations were carried
      out by using density functional theory with plane waves and pseudopotentials. A
      norm-conserving pseudopotential specific for the U atom developed in a previous
      work was employed. Because it was not possible to locate H atoms directly from X
      ray diffraction (XRD) data by structure refinement in previous experimental
      studies, all of the positions of the H atoms in the full unit cell were
      determined theoretically. The structural results, including the lattice
      parameters, bond lengths, bond angles, and powder XRD pattern, were found to be
      in good agreement with their experimental counterparts. However, the calculations
      performed using the unit cell designed by Ostanin and Zeller in 2007, involving
      half of the atoms of the full unit cell, led to significant errors in the
      computed powder XRD pattern. Furthermore, Ostanin and Zeller's unit cell contains
      hydronium ions, H3O+, which are incompatible with the experimental information.
      Therefore, while the use of this schoepite model may be a very useful
      approximation requiring a much smaller amount of computational effort, the full
      unit cell should be used to study this mineral accurately. The Raman spectrum was
      also computed by means of density functional perturbation theory and compared
      with the experimental spectrum. The results were also in agreement with the
      experimental data. A normal-mode analysis of the theoretical spectra was
      performed to assign the main bands of the Raman spectrum. This assignment
      significantly improved the current empirical assignment of the bands of the Raman
      spectrum of schoepite mineral. In addition, the equation of state and elastic
      properties of this mineral were determined. The crystal structure of schoepite
      was found to be stable mechanically and dynamically. Schoepite can be described
      as a brittle material exhibiting small anisotropy and large compressibility in
      the direction perpendicular to the layers, which characterize its structure. The
      calculated bulk modulus, B, was ~35 GPa.

PMID- 29601188
TI  - Exploiting Ancillary Ligation To Enable Nickel-Catalyzed C-O Cross-Couplings of
      Aryl Electrophiles with Aliphatic Alcohols.
AB  - The use of (L)Ni( o-tolyl)Cl precatalysts (L = PAd-DalPhos or CyPAd-DalPhos)
      enables the C( sp2)-O cross-coupling of primary, secondary, or tertiary aliphatic
      alcohols with (hetero)aryl electrophiles, including unprecedented examples of
      such nickel-catalyzed transformations employing (hetero)aryl chlorides,
      sulfonates, and pivalates. In addition to offering a competitive alternative to
      palladium catalysis, this work establishes the feasibility of utilizing ancillary
      ligation as a complementary means of promoting challenging nickel-catalyzed C(
      sp2)-O cross-couplings, without recourse to precious-metal photoredox catalytic
      methods.

PMID- 29601187
TI  - Characterization of Tetrahydrolipstatin and Stereoderivatives on the Inhibition
      of Essential Mycobacterium tuberculosis Lipid Esterases.
AB  - Tetrahydrolipstatin (THL) is a covalent inhibitor of many serine esterases. In
      mycobacteria, THL has been found to covalently react with 261 lipid esterases
      upon treatment of Mycobacterium bovis cell lysate. However, the covalent adduct
      is considered unstable in some cases because of the hydrolysis of the enzyme
      linked THL adduct resulting in catalytic turnover. In this study, a library of
      THL stereoderivatives was tested against three essential Mycobacterium
      tuberculosis lipid esterases of interest for drug development to assess how the
      stereochemistry of THL affects respective enzyme inhibition and allows for cross
      enzyme inhibition. The mycolyltransferase Antigen 85C (Ag85C) was found to be
      stereospecific with regard to THL; covalent inhibition occurs within minutes and
      was previously shown to be irreversible. Conversely, the Rv3802 phospholipase
      A/thioesterase was more accepting of a variety of THL configurations and uses
      these compounds as alternative substrates. The reaction of the THL
      stereoderivatives with the thioesterase domain of polyketide synthase 13 (Pks13
      TE) also leads to hydrolytic turnover and is nonstereospecific but occurs on a
      slower, multihour time scale. Our findings suggest the stereochemistry of the
      beta-lactone ring of THL is important for cross enzyme reactivity, while the two
      stereocenters of the peptidyl arm can affect enzyme specificity and the catalytic
      hydrolysis of the beta-lactone ring. The observed kinetic data for all three
      target enzymes are supported by recently published X-ray crystal structures of
      Ag85C, Rv3802, and Pks13-TE. Insights from this study provide a molecular basis
      for the kinetic modulation of three essential M. tuberculosis lipid esterases by
      THL and can be applied to increase potency and enzyme residence times and enhance
      the specificity of the THL scaffold.

PMID- 29601189
TI  - The True Catalyst Revealed: The Intervention of Chiral Ca and Mg Phosphates in
      Bronsted Acid Promoted Asymmetric Mannich Reactions.
AB  - The acetylacetone-benzaldimine Mannich reaction catalyzed by Mg(II) and Ca(II)
      salts of chiral phosphoric acids (CPA) has been investigated computationally by
      QM/MM methods. Enantioselectivity in this reaction is both larger than and in the
      opposite sense to that observed for the same reaction catalyzed by the protic CPA
      catalyst alone. We present a mechanistic model from which the characteristic
      differences between these metal and metal-free catalysts, which can coexist in
      the same reaction mixture, can be understood. Alkaline earth salts with chiral
      phosphate counterions are found to be more catalytically active than the protic
      form, and the Ca(II) and Mg(II) CPA salts react via different mechanisms, with a
      higher coordination number favored by calcium over magnesium. In the well-ordered
      chiral cavities around these metal centers, asymmetric induction arises from the
      steric interaction with the imine protecting group in the unfavorable pathway,
      with both substrates adopting well-defined conformations. These mechanistic
      models have allowed us to rationalize the stereochemical outcome across a range
      of bimolecular reactions promoted by divalent metal phosphates formed with
      different CPAs.

PMID- 29601190
TI  - Access to Wieland-Miescher Diketone-Derived Building Blocks by Stereoselective
      Construction of the C-9 Quaternary Carbon Center Using the Mukaiyama Aldol
      Reaction.
AB  - The Mukaiyama aldol reaction has been used to efficiently install a lateral chain
      at the C-9 position of the Wieland-Miescher ketone derivative 3 within two steps,
      representing a shortcut compared to that of the classical sequences. The
      treatment of the silylated enol ether 8 with a wide range of acetals in the
      presence of tin tetrachloride led to a the diastereoselective construction of the
      C-9 quaternary center of 33 new building blocks derived from the Wieland-Miescher
      ketone derivative 3.

PMID- 29601191
TI  - Selective Gene Delivery for Integrating Exogenous DNA into Plastid and
      Mitochondrial Genomes Using Peptide-DNA Complexes.
AB  - Selective gene delivery into organellar genomes (mitochondrial and plastid
      genomes) has been limited because of a lack of appropriate platform technology,
      even though these organelles are essential for metabolite and energy production.
      Techniques for selective organellar modification are needed to functionally
      improve organelles and produce transplastomic/transmitochondrial plants. However,
      no method for mitochondrial genome modification has yet been established for
      multicellular organisms including plants. Likewise, modification of plastid
      genomes has been limited to a few plant species and algae. In the present study,
      we developed ionic complexes of fusion peptides containing organellar targeting
      signal and plasmid DNA for selective delivery of exogenous DNA into the plastid
      and mitochondrial genomes of intact plants. This is the first report of exogenous
      DNA being integrated into the mitochondrial genomes of not only plants, but also
      multicellular organisms in general. This fusion peptide-mediated gene delivery
      system is a breakthrough platform for both plant organellar biotechnology and
      gene therapy for mitochondrial diseases in animals.

PMID- 29601192
TI  - Cs2Ge3In6Se14: A Structure Transformation Driven by the Size Preference and Its
      Properties.
AB  - The new selenide Cs2Ge3In6Se14, featuring its own structure type with germanium
      in mixed-valence states, is discovered via a solid-state reaction at 1173 K. The
      compound crystallizes in the R3 m space group with a = 7.9951(6) A and c =
      41.726(4) A. Two adjacent condensed layers of InSe4 tetrahedra are linked by a
      [Ge2+Se6] octahedron into a double slice that is further stacked along the c
      direction with a packing sequence of ... abca... through the [Ge3+2Se6] dimer via
      its Ge-Ge metallic bond. The coexistence of Ge2+/Ge3+ and Ge-Ge metallic bonding
      has been confirmed by XPS and ELF analyses, respectively. More interestingly,
      although sharing many structure similarities, Cs2Ge3In6Se14 and our previously
      reported Cs2Ge3In6Te14 reveal a R3 m to P3 m1 structure transformation with a
      tripled c parameter. Single-crystal diffraction data and a thorough structure
      survey of related compounds point out that such a transformation is driven by the
      size preference of the [Ge2Q6] dimer. The title compound possesses a band gap of
      2.08 eV and shows photodegradation of RhB under visible light that is more
      efficient than that for the commercial P25.

PMID- 29601193
TI  - Mechanism and Origins of Stereoinduction in an Asymmetric Friedel-Crafts
      Alkylation Reaction of Chalcone Catalyzed by Chiral N, N'-Dioxide-Sc(III)
      Complex.
AB  - The mechanism and selectivity of the asymmetric Friedel-Crafts (F-C) alkylation
      reaction between indole and chalcone catalyzed by chiral N, N'-dioxide-Sc(III)
      complexes were investigated at the M06/6-311+G(d,p)//M06/[LANL2DZ,6
      31G(d)](SMD,CH2Cl2) level. The reaction occurred via a three-step mechanism: (i)
      the C3-Cbeta bond formation by interacting the most mucleophilic C3 center of
      indole with the most electrophilic Cbeta center of chalcone; (ii) the abstraction
      of the proton at the C3 atom of indole by counterion OTf-; (iii) proton transfer
      from HOTf to the Calpha atom of chalcone, generating the F-C alkylation product.
      The reaction preferred to occur along the favorable re-face attack pathway,
      producing the dominant R-product. The turnover frequency (TOF) of catalysis was
      predicted to be 1.59 * 10-7 s-1, with a rate constant of K( T) = 1.58 * 10-7 exp(
      29057/ RT) dm6.mol-2.s-1 over the temperature range of 248-368 K. Activation
      strain model (ASM) and energy decomposition analysis (EDA), as well as
      noncovalent interaction (NCI) analysis, for the stereocontrolling transition
      state revealed that the substituent attached to the N atom of the amide subunits
      as well as the amino acid backbone of ligand played important roles in chiral
      inductivity. The benzyl group with structural flexibility tended to form strong
      pi-pi stacking with substrate as well as the terminal phenyl group of chalcone,
      stabilizing re-face attack transition state.

PMID- 29601194
TI  - Electronic Properties of N-Heterocyclic Carbenes and Their Experimental
      Determination.
AB  - N-Heterocyclic carbenes (NHCs) have become without doubt one of the most exciting
      and popular species in chemical science due to the ease of their preparation and
      modularity in stereoelectronic properties. Numerous types of NHCs have been
      prepared, and various experimental methodologies have been proposed for the study
      of their electronic properties in order to rationalize reactivities observed. The
      objective of this article is to provide a comprehensive overview of the most
      common and popular ones among them. In particular, these include the nickel(0)
      based TEP, its rhodium(I) and iridium(I) variants, LEP and related
      electrochemical methods, the palladium(II)-based HEP, phosphinidene- and
      selenourea-based methods, as well as the use of direct 1 J(C-H) coupling
      constants of the precarbene carbon in azolium salts. Each individual method and
      the underlying principle of detection it utilizes will be critically discussed in
      terms of strength and weakness. In addition, comprehensive amounts of data from
      various NHCs are compiled for the purpose of comparison. These are also meant to
      help the scientist in better understanding their own research data and possibly
      providing directions for their future research, which rely on the unique
      electronic properties of NHCs.

PMID- 29601195
TI  - Biosynthesis of Translation Inhibitor Klebsazolicin Proceeds through
      Heterocyclization and N-Terminal Amidine Formation Catalyzed by a Single YcaO
      Enzyme.
AB  - Klebsazolicin (KLB) is a recently discovered Klebsiella pneumonia peptide
      antibiotic targeting the exit tunnel of bacterial ribosome. KLB contains an N
      terminal amidine ring and four azole heterocycles installed into a ribosomally
      synthesized precursor by dedicated maturation machinery. Using an in vitro system
      for KLB production, we show that the YcaO-domain KlpD maturation enzyme is a
      bifunctional cyclodehydratase required for the formation of both the core
      heterocycles and the N-terminal amidine ring. We further demonstrate that the
      amidine ring is formed concomitantly with proteolytic cleavage of azole
      containing pro-KLB by a cellular protease TldD/E. Members of the YcaO family are
      diverse enzymes known to activate peptide carbonyls during natural product
      biosynthesis leading to the formation of azoline, macroamidine, and thioamide
      moieties. The ability of KlpD to simultaneously perform two distinct types of
      modifications is unprecedented for known YcaO proteins. The versatility of KlpD
      opens up possibilities for rational introduction of modifications into various
      peptide backbones.

PMID- 29601196
TI  - Selective Photo-Induced Oxidation with O2 of a Non-Heme Iron(III) Complex to a
      Bis(imine-pyridyl)iron(II) Complex.
AB  - Non-heme iron(II) complexes of pentadentate N4Py ( N,N-bis(2-pyridylmethyl)- N
      bis(2-pyridyl)methylamine) type ligands undergo visible light-driven oxidation to
      their iron(III) state in the presence of O2 without ligand degradation. Under
      mildly basic conditions, however, highly selective base catalyzed ligand
      degradation with O2, to form a well-defined pyridyl-imine iron(II) complex and an
      iron(III) picolinate complex, is accelerated photochemically. Specifically, a
      pyridyl-CH2 moiety is lost from the ligand, yielding a potentially N4
      coordinating ligand containing an imine motif. The involvement of reactive oxygen
      species other than O2 is excluded; instead, deprotonation at the benzylic
      positions to generate an amine radical is proposed as the rate determining step.
      The selective nature of the transformation holds implications for efforts to
      increase catalyst robustness through ligand design.

PMID- 29601197
TI  - Estimating Missing Unit Process Data in Life Cycle Assessment Using a Similarity
      Based Approach.
AB  - In life cycle assessment (LCA), collecting unit process data from the empirical
      sources (i.e., meter readings, operation logs/journals) is often costly and time
      consuming. We propose a new computational approach to estimate missing unit
      process data solely relying on limited known data based on a similarity-based
      link prediction method. The intuition is that similar processes in a unit process
      network tend to have similar material/energy inputs and waste/emission outputs.
      We use the ecoinvent 3.1 unit process data sets to test our method in four steps:
      (1) dividing the data sets into a training set and a test set; (2) randomly
      removing certain numbers of data in the test set indicated as missing; (3) using
      similarity-weighted means of various numbers of most similar processes in the
      training set to estimate the missing data in the test set; and (4) comparing
      estimated data with the original values to determine the performance of the
      estimation. The results show that missing data can be accurately estimated when
      less than 5% data are missing in one process. The estimation performance
      decreases as the percentage of missing data increases. This study provides a new
      approach to compile unit process data and demonstrates a promising potential of
      using computational approaches for LCA data compilation.

PMID- 29601198
TI  - A Generalized-Rate Model for Describing and Scaling Redox Kinetics in Sediments
      Containing Variable Redox-Reactive Materials.
AB  - This study developed a generalized modeling approach for describing and scaling
      redox reactions from reactive components to the sediments and their assemblages,
      using Cr(VI) reduction as an example. Batch experiments were performed to
      characterize the rates of Cr(VI) reduction in four Fe(II)-containing sediments
      and their assemblages. The experimental data were first used to calibrate a
      generalized-rate model of Cr(VI) reduction with generic rate parameters. The
      generalized-rate model was then used to describe the kinetics of Cr(VI) reduction
      in the sediment assemblages by linearly scaling the rate parameters from the
      individual sediments. Via comparison with the experimental results, this study
      found that the generalized-rate model with generic rate parameters can describe
      Cr(VI) reduction in individual sediments and their assemblages with different
      redox reactivity toward Cr(VI) reduction. The sediment-associated Fe(II) and its
      reactivity were found to be the key variables in the generalized model for
      describing the Cr(VI) reduction in the studied sediments. A three-step extraction
      method was subsequently developed to estimate the rate-specific Fe(II) pools that
      can facilitate the application of the scaling approach in field systems.

PMID- 29601199
TI  - Genetically Encoding Fluorosulfate-l-tyrosine To React with Lysine, Histidine,
      and Tyrosine via SuFEx in Proteins in Vivo.
AB  - Introducing new chemical reactivity into proteins in living cells would endow
      innovative covalent bonding ability to proteins for research and engineering in
      vivo. Latent bioreactive unnatural amino acids (Uaas) can be incorporated into
      proteins to react with target natural amino acid residues via proximity-enabled
      reactivity. To expand the diversity of proteins amenable to such reactivity in
      vivo, a chemical functionality that is biocompatible and able to react with
      multiple natural residues under physiological conditions is highly desirable.
      Here we report the genetic encoding of fluorosulfate-l-tyrosine (FSY), the first
      latent bioreactive Uaa that undergoes sulfur-fluoride exchange (SuFEx) on
      proteins in vivo. FSY was found nontoxic to Escherichia coli and mammalian cells;
      after being incorporated into proteins, it selectively reacted with proximal
      lysine, histidine, and tyrosine via SuFEx, generating covalent intraprotein
      bridge and interprotein cross-link of interacting proteins directly in living
      cells. The proximity-activatable reactivity, multitargeting ability, and
      excellent biocompatibility of FSY will be invaluable for covalent manipulation of
      proteins in vivo. Moreover, genetically encoded FSY hereby empowers general
      proteins with the next generation of click chemistry, SuFEx, which will afford
      broad utilities in chemical biology, drug discovery, and biotherapeutics.

PMID- 29601200
TI  - Gluco-1 H-imidazole: A New Class of Azole-Type beta-Glucosidase Inhibitor.
AB  - Gluco-azoles competitively inhibit glucosidases by transition-state mimicry and
      their ability to interact with catalytic acid residues in glucosidase active
      sites. We noted that no azole-type inhibitors described, to date, possess a
      protic nitrogen characteristic for 1 H-imidazoles. Here, we present gluco-1 H
      imidazole, a gluco-azole bearing a 1 H-imidazole fused to a glucopyranose
      configured cyclitol core, and three close analogues as new glucosidase
      inhibitors. All compounds inhibit human retaining beta-glucosidase, GBA1, with
      the most potent ones inhibiting this enzyme (deficient in Gaucher disease) on a
      par with glucoimidazole. None inhibit glucosylceramide synthase, cytosolic beta
      glucosidase GBA2 or alpha-glucosidase GAA. Structural, physical and computational
      studies provide first insights into the binding mode of this conceptually new
      class of retaining beta-glucosidase inhibitors.

PMID- 29601201
TI  - The Pentagonal Nature of Self-Assembled Silicon Chains and Magic Clusters on
      Ag(110).
AB  - The atomic structures of self-assembled silicon nanoribbons and magic clusters on
      Ag(110) substrate have been studied by high-resolution noncontact atomic force
      microscopy (nc-AFM) and tip-enhanced Raman spectroscopy (TERS). Pentagon-ring
      structures in Si nanoribbons and clusters have been directly visualized.
      Moreover, the vibrational fingerprints of individual Si nanoribbon and cluster
      retrieved by subnanometer resolution TERS confirm the pentagonal nature of both
      Si nanoribbons and clusters. This work demonstrates that Si pentagon can be an
      important element in building silicon nanostructures, which may find important
      applications for future nanoelectronic devices based on silicon.

PMID- 29601202
TI  - Benchmarking the Effective Fragment Potential Dispersion Correction on the S22
      Test Set.
AB  - The usual modeling of dispersion interactions in density functional theory (DFT)
      is often limited by the use of empirically fitted parameters. In this study, the
      accuracies of the popular empirical dispersion corrections and the first
      principles derived effective fragment potential (EFP) dispersion correction are
      compared by computing the DFT-D and HF-D equilibria interaction energies and
      intermolecular distances of the S22 test set dimers. Functionals based on the
      local density approximation (LDA) and generalized gradient approximation (GGA),
      as well as hybrid functionals, are compared for the DFT-D calculations using
      coupled cluster CCSD(T) at the complete basis set (CBS) limit as the reference
      method. In general, the HF-D(EFP) method provides accurate equilibrium
      dimerization energies and intermolecular distances for hydrogen-bonded systems
      compared to the CCSD(T)/CBS reference data without using any empirical
      parameters. For dispersion-dominant and mixed systems, the structures and
      interaction energies obtained with the B3LYP-D(EFP) method are similar to or
      better than those obtained with the other DFT-D and HF-D methods. Overall, the
      first-principles derived -D(EFP) correction presents a robust alternative to the
      empirical -D corrections when used with the B3LYP functional for dispersion
      dominant and mixed systems or with Hartree-Fock for hydrogen-bonded systems.

PMID- 29601203
TI  - Crystallography and Molecular Arrangement of Polymorphic Monolayer J-Aggregates
      of a Cyanine Dye: Multiangle Polarized Light Fluorescence Optical Microscopy
      Study.
AB  - The molecular orientation in monolayer J-aggregates of 3,3-di(gamma-sulfopropyl)
      5,5-dichlorotiamonomethinecyanine dye has been precisely estimated using improved
      linear polarization measurements in the fluorescence microscope in which a
      multiangle set of polarization data is obtained using sample rotation. The
      estimated molecular orientation supplemented with the previously established
      crystallographic constraints based on the analysis of the well-developed two
      dimensional J-aggregate shapes unambiguously indicate the staircase type of
      molecular arrangement for striplike J-aggregates with the staircases oriented
      along strips. The molecular transition dipoles are inclined at an angle of ~25
      degrees  to the strip direction, whereas the characteristic strip vertex angle
      ~45 degrees  is formed by the [100] and [1-10] directions of the monoclinic unit
      cell. Measurements of the geometry of partially unwound tubes and their
      polarization properties support the model of tube formation by close-packed
      helical winding of flexible monolayer strips. In the tubes, the long molecular
      axes are oriented at a small angle in the range of 5-15 degrees  to the normal to
      the tube axis providing low bending energy. At a nanoscale, high-resolution
      atomic force microscopy imaging of J-aggregate monolayers reveals a complex quasi
      one-dimensional organization.

PMID- 29601204
TI  - pH-Dependence of Binding Constants and Desorption Rates of Phosphonate- and
      Hydroxamate-Anchored [Ru(bpy)3]2+ on TiO2 and WO3.
AB  - The binding constants and rate constants for desorption of the modified molecular
      dye [Ru(bpy)3]2+ anchored by either phosphonate or hydroxamate on the bipyridine
      ligand to anatase TiO2 and WO3 have been measured. In aqueous media at pH 1-10,
      repulsive electrostatic interactions between the negatively charged anchor and
      the negatively charged surface govern phosphonate desorption under neutral and
      basic conditions for TiO2 anatase due to the high acidity of phosphonic acid (p
      Ka,4 = 5.1). In contrast, the lower acidity of hydroxamate (p Ka,1 = 6.5, p Ka,2
      = 9.1) leads to little change in adsorption/desorption properties as a function
      of pH from 1 to 7. The binding constant for hydroxamate is 103 in water,
      independent of pH in this range. These results are true for WO3 as well, but are
      not reported at pH > 4 due to its Arrhenius acidity. Kinetics for desorption as a
      function of pH are reported, with a proposed mechanism for phosphonate desorption
      at high pH being the electrostatic repulsion of negative charges between the
      surface and the anionic anchor. Further, the hydroxamic acid anchor itself is
      likely the site of quasi-reversible redox activity in [Ru(bpy)2(2,2'-bpy-4,4'
      (C(O)N(OH))2)]2+, which does not lead to any measurable deterioration of the
      complex within 2 h of dark cyclic voltammogram scans in aqueous media. These
      results posit phosphonate as the preferred anchoring group under acidic
      conditions and hydroxamate for neutral/basic conditions.

PMID- 29601205
TI  - Efficient Extraction of Light from a Nitrogen-Vacancy Center in a Diamond
      Parabolic Reflector.
AB  - Quantum emitters in solids are being developed for a range of quantum
      technologies, including quantum networks, computing, and sensing. However, a
      remaining challenge is the poor photon collection due to the high refractive
      index of most host materials. Here we overcome this limitation by introducing
      monolithic parabolic reflectors as an efficient geometry for broadband photon
      extraction from quantum emitter and experimentally demonstrate this device for
      the nitrogen-vacancy (NV) center in diamond. Simulations indicate a photon
      collection efficiency exceeding 75% across the visible spectrum and experimental
      devices, fabricated using a high-throughput gray scale lithography process,
      demonstrating a photon extraction efficiency of (41 +/- 5)%. This device enables
      a raw experimental detection efficiency of (12 +/- 1)% with fluorescence
      detection rates as high as (4.114 +/- 0.003) * 106 counts per second (cps) from a
      single NV center. Enabled by our deterministic emitter localization and
      fabrication process, we find a high number of exceptional devices with an average
      count rate of (3.1 +/- 0.9) * 106 cps.

PMID- 29601206
TI  - Non-Plasmonic SERS with Silicon: Is It Really Safe? New Insights into the
      Optothermal Properties of Core/Shell Microbeads.
AB  - Silicon is one of the most interesting candidates for plasmon-free surface
      enhaced Raman scattering (SERS), because of its high-refractive index and thermal
      stability. However, here we demonstrate that the alleged thermal stability of
      silicon nanoshells irradiated by conventional Raman laser cannot be taken for
      granted. We investigated the opto-thermal behavior of SiO2/Si core/shell
      microbeads (Si-rex) irradiated with three common Raman laser sources (lambda =
      532, 633, 785 nm) under real working conditions. We obtained an experimental
      proof of the critical role played by bead size and aggregation in heat and light
      management, demonstrating that, in the case of strong opto-thermal coupling, the
      temperature can exceed that of the melting points of both core and shell
      components. In addition, we also show that weakly coupled beads can be utilized
      as stable substrates for plasmon-free SERS experiments.

PMID- 29601207
TI  - Nonsurgical Treatments of Patellar Tendinopathy: Multiple Injections of Platelet
      Rich Plasma Are a Suitable Option: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Patellar tendinopathy is a condition characterized by anterior knee
      activity-related pain. It has a high incidence among athletes engaged in jumping
      sports and may become a chronic condition. Nonoperative management is the first
      choice in these patients, and several nonsurgical treatment options have been
      proposed. Nonetheless, clear indications on the most effective approach to
      address patellar tendinopathy are still lacking. PURPOSE: To analyze the evidence
      on nonoperative options to treat chronic patellar tendinopathy through a
      systematic review of the literature and to perform a meta-analysis to identify
      the most effective nonsurgical option. STUDY DESIGN: Systematic review and meta
      analysis. METHODS: The search was conducted with the PubMed and Cochrane
      databases on January 4, 2017. All clinical English-language reports of any level
      of evidence on nonsurgical treatment of patellar tendinopathy were included. The
      quality of each article was assessed by use of the Coleman score. A meta-analysis
      was performed on all articles reporting the Victorian Institute of Sport
      Assessment scale for patellar tendinopathy to evaluate the results of the most
      described treatments. RESULTS: A total of 70 studies involving 2530 patients were
      included in the qualitative data synthesis. The Coleman score showed an overall
      poor study quality. The most described treatment groups that could be included in
      the meta-analysis were reported in 22 studies on eccentric exercise,
      extracorporeal shockwave therapy (ESWT), and platelet-rich plasma (PRP). Single
      and multiple PRP injections were evaluated separately. Eccentric exercise
      therapies obtained the best results ( P < .05) at short-term (<6 months, mean 2.7
      +/- 0.7 months). However, multiple injections of PRP obtained the best results (
      P < .05), followed by ESWT and eccentric exercise, at long-term follow-up (>=6
      months, mean 15.1 +/- 11.3 months). CONCLUSION: The literature documents several
      nonsurgical approaches for the treatment of chronic patellar tendinopathy with
      important limitations in terms of study quality. The available evidence showed an
      overall positive outcome, but some differences have been highlighted. Eccentric
      exercises may seem the strategy of choice in the short-term, but multiple PRP
      injections may offer more satisfactory results at long-term follow-up and can be
      therefore considered a suitable option for the treatment of patellar
      tendinopathy.

PMID- 29601208
TI  - Performance and Return to Sport After Tommy John Surgery Among Major League
      Baseball Position Players.
AB  - BACKGROUND: The anterior bundle of the medial ulnar collateral ligament (UCL) is
      the primary restraint to valgus stress at the elbow and is often injured among
      overhead throwing athletes. Despite prevention strategies, injuries to the elbow
      UCL are on the rise. PURPOSE: To determine (1) the return-to-sport (RTS) rate of
      Major League Baseball (MLB) position players after elbow medial UCL
      reconstruction, (2) postoperative career length and games per season, (3) pre-
      and postoperative performance, (4) postoperative performance versus matched
      control players, and (5) whether position players changed positions after UCL
      reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: MLB
      players who underwent elbow UCL reconstruction were identified (cases).
      Demographic and performance data were collected for each player. Matched controls
      were identified. RTS in MLB was defined as playing in at least 1 MLB game after
      UCL reconstruction. Comparisons between case and control groups and pre- and
      postoperative time points were made via paired samples Student t tests. RESULTS:
      Thirty-three players (34 surgical procedures) were identified with a mean +/- SD
      age of 30.2 +/- 4.2 years and a mean experience in the MLB of 6.3 +/- 3.9 years
      at the time of surgery. Twenty-eight players (84.8%) were able to RTS in MLB at a
      mean 336.9 +/- 121.8 days. However, players >=30 years old demonstrated a
      significantly lower RTS rate (53.3%) than players <30 years old (89.4%; P < .05).
      Catchers had a significantly shorter postoperative career length (2.8 +/- 1.8
      years) versus matched controls (6.1 +/- 1.9 years; P < .05). Outfielders had a
      significantly lower wins above replacement postoperatively (0.8 +/- 0.7) versus
      preoperatively (1.5 +/- 1.1; P < .05). There were no performance differences
      between cases and matched controls. Twelve players (48%) returned to a different
      position postoperatively. CONCLUSION: The RTS rate for MLB position players after
      elbow UCL reconstruction is similar to that of pitchers. Catchers had a
      significantly shorter career length than that of matched controls. Outfielders
      performed worse postoperatively versus preoperatively. There is a high rate of
      position change after Tommy John surgery for infielders and outfielders.

PMID- 29601209
TI  - Changes in mood after screening for antenatal anxiety and depression.
AB  - BACKGROUND: Screening programmes with referral are a valuable strategy for
      mitigating consequences of perinatal depression on mothers and their families.
      The effectiveness of these screening programmes needs to be measured. One
      potential problem in assessing outcomes is measurement reactivity where the
      actual measure results in changes in the people being measured. AIM: The aim of
      this article is to explain the mechanisms and circumstances by which measurement
      reactivity occurred in a sample of antenatal women who participated in a
      screening interview. METHODS: Fifty-five women who participated in an antenatal
      screening interview in their second trimester were re-interviewed in their third
      trimester. These qualitative interviews were conducted between September 2015 and
      April 2016. RESULTS: The qualitative data suggested that measurement reactivity
      occurred through mechanisms such as the disclosure, gaining self-knowledge,
      validation of experiences, and personal agency which resulted in them seeking out
      support from others. CONCLUSION: Although the screening interview appeared to
      improve women's outcomes, this may have occurred through measurement reactivity.
      This needs to be considered when designing studies that aim to assess the
      effectiveness of screening with intervention for antenatal depression.

PMID- 29601210
TI  - Applications of UV/Vis Spectroscopy in Characterization and Catalytic Activity of
      Noble Metal Nanoparticles Fabricated in Responsive Polymer Microgels: A Review.
AB  - Noble metal nanoparticles loaded smart polymer microgels have gained much
      attention due to fascinating combination of their properties in a single system.
      These hybrid systems have been extensively used in biomedicines, photonics, and
      catalysis. Hybrid microgels are characterized by using various techniques but
      UV/Vis spectroscopy is an easily available technique for characterization of
      noble metal nanoparticles loaded microgels. This technique is widely used for
      determination of size and shape of metal nanoparticles. The tuning of optical
      properties of noble metal nanoparticles under various stimuli can be studied
      using UV/Vis spectroscopic method. Time course UV/Vis spectroscopy can also be
      used to monitor the kinetics of swelling and deswelling of microgels and hybrid
      microgels. Growth of metal nanoparticles in polymeric network or growth of
      polymeric network around metal nanoparticle core can be studied by using UV/Vis
      spectroscopy. This technique can also be used for investigation of various
      applications of hybrid materials in catalysis, photonics, and sensing. This
      tutorial review describes the uses of UV/Vis spectroscopy in characterization and
      catalytic applications of responsive hybrid microgels with respect to recent
      research progress in this area.

PMID- 29601211
TI  - Food insecurity and coping strategies in a marine protected area in southeastern
      Tanzania.
AB  - This article examines the perceived food security and coping strategies in
      coastal communities located in a marine protected area (MPA) in southeastern
      Tanzania. Drawing on fieldwork concentrated in a representative coastal village,
      the article illustrates how women in particular understand their food security
      situation in relation to the MPA. Data from interviews with 120 women suggest
      that the majority of the households in the study area were food insecure. Only
      few respondents, however, specifically attributed their food insecurity to the
      MPA's presence in their village, suggesting that food security is
      multidimensional and is undergirded by several interrelated factors that vary
      over time. The findings query the assertion that MPAs can and do contribute to
      improved food security in coastal populations through increased fish biomass or
      ecotourism projects.

PMID- 29601213
TI  - It's Time to Develop a New "Draft Test Protocol" for a Mars Sample Return Mission
      (or Two...).
AB  - The last time NASA envisioned a sample return mission from Mars, the development
      of a protocol to support the analysis of the samples in a containment facility
      resulted in a "Draft Test Protocol" that outlined required preparations "for the
      safe receiving, handling, testing, distributing, and archiving of martian
      materials here on Earth" (Rummel et al., 2002 ). This document comprised a
      specific protocol to be used to conduct a biohazard test for a returned martian
      sample, following the recommendations of the Space Studies Board of the US
      National Academy of Sciences. Given the planned launch of a sample-collecting and
      sample-caching rover (Mars 2020) in 2 years' time, and with a sample return
      planned for the end of the next decade, it is time to revisit the Draft Test
      Protocol to develop a sample analysis and biohazard test plan to meet the needs
      of these future missions. Key Words: Biohazard detection-Mars sample analysis
      Sample receiving facility-Protocol-New analytical techniques-Robotic sample
      handling. Astrobiology 18, 377-380.

PMID- 29601212
TI  - Measurable Residual Disease at Induction Redefines Partial Response in Acute
      Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without
      NPM1 Mutations.
AB  - Purpose We investigated the effect on outcome of measurable or minimal residual
      disease (MRD) status after each induction course to evaluate the extent of its
      predictive value for acute myeloid leukemia (AML) risk groups, including NPM1
      wild-type (wt) standard risk, when incorporated with other induction response
      criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients
      with AML or high-risk myelodysplastic syndrome had prospective multiparameter
      flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were
      categorized as resistant disease (RD), partial remission (PR), and complete
      remission (CR) or complete remission with absolute neutrophil count < 1,000/uL or
      thrombocytopenia < 100,000/MUL (CRi) by clinicians, with CR/CRi subdivided by MFC
      MRD assay into MRD+ and MRD-. Patients without high-risk factors, including Flt3
      internal tandem duplication wt/- NPM1-wt subgroup, received a second
      daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for
      patients with high-risk factors. Results Survival outcomes from PR and MRD+
      responses after C1 were similar, particularly for good- to standard-risk
      subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD-; P
      < .001). Adjusted analyses confirmed significant OS differences between C1 RD
      versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v
      45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect
      of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P
      < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant
      when adjusting for C1 response. MRD positivity appeared less discriminatory in
      poor-risk patients by stratified analyses. For the NPM1-wt standard-risk
      subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v
      63% MRD-, P = .003; relapse incidence, 89% when MRD+ >= 0.1%); transplant benefit
      was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than
      those with MRD- (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction).
      Conclusion MFC-MRD can improve outcome stratification by extending the definition
      of partial response after first induction and may help predict NPM1-wt standard
      risk patients with poor outcome who benefit from transplant in the first CR.

PMID- 29601214
TI  - A novel clinical test for assessing patellar cartilage changes and its
      correlation with magnetic resonance imaging and arthroscopy.
AB  - Controversy still exists regarding the best clinical assessment test for
      chondromalacia patellae (CMP). Our study aims to evaluate the specificity and
      sensitivity of a novel clinical test for CMP, the "Patella Slide Test" (PST)
      against the findings of magnetic resonance imaging (MRI) and arthroscopy. We
      included 221 consecutive patients planned for elective knee arthroscopic surgery.
      An MRI scan of the symptomatic knee was performed prior to surgery. On the day of
      surgery, each patient was examined using the PST followed by a knee arthroscopy
      to assess the quality of the chondral surfaces of the patellofemoral joint. The
      MRI and PST results were compared against the arthroscopic findings that served
      as the gold standard. The PST (0.89) was statistically more sensitive than MRI
      (0.67) in diagnosing CMP. The PST (0.89) also had a greater negative predictive
      value (NPV) than MRI (0.74). However, MRI (0.94) was more specific than the PST
      (0.85). The differences in accuracy and positive predictive value of the PST
      versus MRI were not statically significant. In conclusion, the PST shows high
      sensitivity and has a greater NPV than MRI as a clinical test for diagnosing CMP.

PMID- 29601215
TI  - Prevalence of Cleft Lip/Palate in the Fangshan District of Beijing, 2006-2012.
AB  - OBJECTIVE: To estimate the cleft lip with or without cleft palate (CL/P)
      prevalence among births between 2006 and 2012 in Fangshan district of Beijing,
      China. DESIGN: Surveillance data analysis. SETTING: All hospitals that provide
      obstetric services in the district. PATIENTS: The CL/P cases presented for this
      report were from 13 weeks' gestation to 7 days postpartum. MAIN OUTCOME MEASURES:
      The CL/P prevalence was defined as the number of cases per 10 000 births,
      including live births and stillbirths at 28 weeks' gestation or beyond. RESULTS:
      The overall CL/P prevalence was 18.9 (95% confidence interval [CI]: 15.1-22.7)
      per 10 000 births. From 2006 to 2012, the CL/P prevalence was 19.3, 20.2, 10.9,
      16.1, 17.5, 25.4, and 22.3 per 10 000 births; annually, no significant change was
      noted ( Pfor trend = .311). The prevalence of cleft palate, cleft lip, and cleft
      lip and palate were 3.4 (95% CI: 2.0-5.4), 6.2 (95% CI: 4.2-8.8), and 9.4 (95%
      CI: 6.9-12.4) per 10 000 births, respectively. The CL/P prevalence among the
      nonpermanent residents (31.4 per 10 000 births) was 2.31 times that of permanent
      residents (13.6 per 10 000 births). Among nonpermanent residents, the CL/P
      prevalence showed an upward trend over the study period ( Pfor trend = .036),
      that increased from 38.8 (95% CI: 16.5-76.6) per 10 000 births in 2006 to 54.6
      (95% CI: 25.7-100.4) per 10 000 births in 2012. CONCLUSIONS: The overall CL/P
      prevalence was stable in the Fangshan district. However, the CL/P prevalence of
      the nonpermanent residents increased significantly.

PMID- 29601216
TI  - Sex/Gender Differences in Screening for Autism Spectrum Disorder: Implications
      for Evidence-Based Assessment.
AB  - Autism spectrum disorder (ASD) is diagnosed more often in boys than in girls;
      however, little is known about the nature of this sex/gender discrepancy or how
      it relates to diagnostic assessment practices. This study examined the
      performance of the Social Communication Questionnaire (SCQ) in screening for ASD
      among boys and girls. Data were drawn from the South Carolina Children's
      Educational Surveillance Study, a population-based study of ASD prevalence among
      children 8-10 years of age. Analyses were conducted using SCQ data from 3,520
      children, with direct assessment data from 272 with elevated SCQ scores. A
      bifactor model based on the Diagnostic and Statistical Manual of Mental
      Disorders's (5th ed.) two ASD symptom domains fit the data well and performed
      slightly better for girls. In the general population sample, girls exhibited
      fewer social communication/interaction and restricted-repetitive behavior
      symptoms than boys. In the direct assessment sample, however, girls with ASD
      showed greater impairment in social communication/interaction than boys with ASD.
      Items pertaining to social communication/interaction problems at ages 4-5 were
      among the most diagnostically efficient overall and particularly for girls.
      Similarly, receiver operating characteristic analyses suggested that the SCQ
      performs adequately among boys and well among girls. Results support the use of
      the SCQ in screening for ASD but do not indicate sex/gender-specific cutoffs.
      Girls with ASD may exhibit pronounced intraindividual deficits in social
      communication/interaction compared to male peers with ASD and female peers
      without ASD. Although more research is needed, careful attention to social
      communication/interaction deficits around 4-5 years of age may be especially
      useful for assessing ASD in girls.

PMID- 29601217
TI  - The effect of patellar taping on lower extremity running kinematics in
      individuals with patellofemoral pain syndrome.
AB  - PURPOSE: To investigate the effects of patellar taping (Leukotape(r) (LT),
      Pinetown, South Africa, Kinesio Tape (KT), Dortmund, Germany, or no tape) on
      lower extremity kinematics in runners with and without patellofemoral pain
      syndrome (PFPS). METHODS: In total, 20 healthy individuals and 12 with PFPS ran
      on a treadmill under different taping conditions and lower extremity kinematics
      and stride characteristics were obtained using Peak Motus Software, Colorado,
      USA. Data were analyzed using descriptive statistics and mixed factorial analysis
      of variance (p < 0.05). RESULTS: Significant taping effects were found for hip
      (F(2,60) = 16.79, p = 0.0001) and knee (F(2,60) = 17.27, p = 0.0001) flexion
      angles at initial contact, and peak hip flexion angles during swing (F(2,60) =
      6.55, p = 0.003). Increased flexion was noted with LT more than KT and no tape
      conditions. Similarly, peak knee flexion angles during stance (F(2,60) = 3.51, p
      = 0.03) and flight time (F(2,60) = 5.01, p = 0.01) revealed significant taping
      effects, with LT resulting in more flexion (p = 0.04) and shorter flight times (p
      = 0.01) than the no tape condition. Furthermore, a significant taping effect was
      seen for peak knee flexion angle during swing (F(2,60) = 4.96, p = 0.01), with
      the KT resulting in less flexion than LT (p = 0.04) and no tape conditions (p =
      0.04). CONCLUSION: The application of tape during running may impact on hip and
      knee flexion angles at initial contact, as well as flight time.

PMID- 29601218
TI  - Treadmill associated head injuries on the rise: an 18 year review of U.S.
      emergency room visits.
AB  - OBJECTIVE: The treadmill is the most commonly used aerobic exercise equipment
      with studies showing many gym-related injuries are attributed to treadmills. The
      purpose of this study is to examine the incidence of treadmill-associated head
      injuries within the US. METHODS: Retrospective data from 1997 to 2014 was
      collected via the National Electronic Injury Surveillance System, which provides
      annual es7timates of injuries associated with consumer products. Patients over 18
      years who sustained treadmill-associated head injuries were included, and the
      estimated annual incidence was determined. RESULTS: An estimated 4929 patients
      presented to US emergency departments with a head injury while exercising on a
      treadmill between 1997 and 2014. A >1000% increase in the number of head injuries
      was observed over the study period (p-value <0.001). Patients over 50 had a 14
      times greater risk of admission than younger patients (p-value <0.001). Injuries
      were greater in women than men. CONCLUSION: Our study demonstrates a significant
      increase treadmill-associated head injuries from 1997 to 2014. This phenomenon is
      most pronounced in older and female populations. The exact etiology of this large
      increase remains unclear. Education on the proper use of treadmills as well as
      further investigation into the cause of the increase are warranted.

PMID- 29601219
TI  - An examination of the perceived impact of a continuing interprofessional
      education experience on opiate prescribing practices.
AB  - Chronic pain is increasingly recognized as a public health problem. We assessed
      the effectiveness of a multi-modal, interprofessional educational approach aimed
      at empowering healthcare professionals to make deliberative changes, especially
      in opiate prescribing practices. Education activities included enduring webcasts,
      regional interprofessional roundtable events, and state-level conference
      presentations within targeted Kentucky and West Virginia regions of the United
      States. Over 1,000 participants accessed the various activities. For the live
      events, the largest groups reached included nurses (38.1%), nurse practitioners
      (31.2%), and physicians (22.1%). In addition to our reach, higher levels of
      educational effectiveness were measured, specifically, learner's intentions to
      change practice patterns, confidence in meeting patient's needs, and knowledge of
      pain management guidelines. The majority of the conference (58%) and roundtable
      (69%) participants stated they intend to make a practice change in one or more
      areas of chronic pain patient management in post-event evaluation. Differences in
      pre- and post-activity responses on the measures of confidence and knowledge,
      with additional comparison to a control population who were not in attendance,
      were analyzed using non-parametric tests of significance. While neither activity
      produced significant changes in confidence from pre-activity, participants were
      more confident post-activity than their control group peers. There were
      significant changes in knowledge for both live event and webcast participants.
      Impactful chronic pain continuing the education that emphasizes collaborative
      care is greatly needed; these results show that the approaches taken here can
      impact learner's knowledge and confidence, and hold potential for creating change
      in how opioid prescribing is managed.

PMID- 29601220
TI  - Is perceived force an accurate method of regulating exercise load for the neck?
AB  - OBJECTIVE: Patient perceived level of force is commonly used to regulate exercise
      load. This study determined the accuracy of perceived force as a method of
      regulating exercise load for the cervical flexors and extensors. METHODS: Thirty
      healthy individuals performed submaximal isometric cervical flexion and extension
      exercise at perceived intensities (25%, 50%, and 75%) of their maximal voluntary
      contraction (MVC) with no feedback in a neck dynamometer. Measurements of
      "actual" versus "perceived" force levels were compared before and after the
      performance of an MVC. Data were analyzed descriptively and the relationship
      between performance error, test, and participant factors examined. RESULTS: With
      the exception of the 25% MVC extension trials post-MVC, an underestimation of
      force was observed over all conditions that worsened as the target force
      increased (50% and 75%) with only some improvement following the experience of an
      MVC (p < 0.001). Linear mixed modeling indicated participants familiar with
      exercise may have better accuracy (p = 0.07). CONCLUSION: Regulating isometric
      resistance exercise load of the neck based on a perceived proportion of MVC force
      may only be accurate at low intensities (25% MVC) but not for moderate to high
      (50-75%) intensities.

PMID- 29601221
TI  - Comparison of hip extensor muscle activity including the adductor magnus during
      three prone hip extension exercises.
AB  - OBJECTIVES: This study compared the role of the adductor magnus muscle (Amag) as
      a hip extensor while performing active prone hip extension (PHE), PHE with hip
      adduction (PHE-ADD), and PHE with hip abduction (PHE-ABD) with the gluteus
      maximus (Gmax) and hamstrings. METHODS: The study recruited 22 healthy
      participants. Electromyography data were recorded from the Amag, Gmax, and medial
      and lateral hamstrings during PHE, PHE-ADD, and PHE-ABD. Normalized
      electromyographic data were examined using one-way, repeated-measures analyses of
      variance. RESULTS: The magnitude of the Amag, Gmax, and hamstring activations did
      not differ significantly while performing PHE (p = 0.41). Furthermore, the Amag
      and hamstring activations were significantly greater than the Gmax activation
      when performing PHE-ADD (p < 0.05). The Gmax showed significantly greater
      activation during PHE-ABD than the Amag and medial and lateral hamstrings (p <
      0.05). CONCLUSIONS: Based on these results, we advocate including the Amag as a
      hip extensor during the PHE test or exercise. Our preliminary results have the
      potential to be applied directly to the PHE test, for investigating the muscle
      activation pattern of the Amag with the Gmax and hamstrings in patients with hip
      or lower back pain.

PMID- 29601222
TI  - Effects of dance-based movement therapy on balance, gait, and psychological
      functions in severe cerebellar ataxia: A case study.
AB  - PURPOSE: Individuals in the later stages of cerebellar ataxia usually experience
      serious balance and immobility problems. Currently, there is a lack of adequate
      rehabilitative programs for individuals with severe cerebellar ataxia that can
      help improve ataxia-related motor impairment. The purpose of the present study
      was to explore the potential physiotherapeutic benefits of partnered dance on
      balance, motor functions, and psychological well-being in an individual
      demonstrating severe cerebellar ataxia symptoms. METHODS: The individual was a 39
      year-old male diagnosed with cerebellar atrophy. He had the disease for more than
      15 years prior to the study. The individual attended 24 intervention sessions
      over an 8-week period of dance-based movement training that aimed to improve his
      balance and postural stability by facilitating the perception and control of
      static and dynamic balance movements and body alignment. RESULTS: The individual
      demonstrated improvements in independent standing balance, gait characteristics,
      and functional mobility. In addition, improvements in self-reported depression
      and quality of life scores were observed after completion of the intervention.
      CONCLUSION: Although interpreting the findings of this study is limited to a
      single participant, partnered dance could be a suitable alternative
      physiotherapeutic intervention method for people with severely impaired mobility
      due to cerebellar dysfunction.

PMID- 29601223
TI  - Providing no-cost transport to patients in an underserved area: Impact on access
      to physical therapy.
AB  - BACKGROUND: Barriers to accessing outpatient health care services are common and
      contribute to poor health outcomes. We describe the efforts of a private practice
      physical therapy (PT) clinic to reduce these barriers by offering a door-to-door
      van service at no cost to patients. METHODS: Clinic records and national census
      databases were retrospectively reviewed to explore the impact of offering no-cost
      van rides to patients attending outpatient PT appointments. We used descriptive
      statistics and linear regression to describe volume of utilization of the van
      service over a 40-month period. Paired t-tests compared PT clinic attendance
      rates (percentage of scheduled visits that were attended) before and after
      implementation of the van service. RESULTS: Use of the van service increased
      significantly over time, from a mean of 83 riders per month in 2010 to 205 riders
      per month in 2013 (p < 0.001). Overall clinic attendance rate increased from
      80.1% to 84.1% after implementation of the service (p = 0.002). Following
      introduction of the van service, 48% of patients using the van, compared to 25%
      of clinic patients overall, were uninsured or insured by Medicaid. CONCLUSION:
      Use of the van service increased over time, and availability of no-cost van
      transportation was associated with increased visit attendance for patients at an
      outpatient PT clinic.

PMID- 29601224
TI  - Physical therapists' perception of workplace ethics in an evolving health-care
      delivery environment: a cross-sectional survey.
AB  - Physical therapists are trained and obligated to deliver optimal health care and
      put patients first above all else. In the changing health-care environment,
      health-care organizations are grappling with controlling cost and increasing
      revenues. Moral distress may be created when physical therapists' desire to
      provide optimal care conflicts with their organization's goals to remain
      financially viable or profitable. Moral distress has been associated with low
      perception of ethical environment, professional burnout, and high turnover in
      organizations. This study identified groups who may be vulnerable to low
      perception of organizational ethical environment and identified self-reported
      strategies to remedy these perceptions. An ethics environment questionnaire was
      mailed to a random sample of 1200 physical therapists in Georgia. Respondents (n
      = 340) were analyzed by age, workplace setting, and position in organization.
      Therapists working in skilled nursing/assisted living environments scored the
      lowest on the questionnaire and voiced concerns regarding their ethical work
      environments. Owners and executives perceived their organizations to be more
      ethical than front-line clinicians. Respondent concerns included high
      productivity standards, aggressive coding/billing policies, decreased
      reimbursement, and increased insurance regulation. Possible solutions included
      more frequent communication between management and clinicians about ethics,
      greater professional autonomy, and increased training in business ethics and
      finance.

PMID- 29601225
TI  - Functional basic reading skills in Williams syndrome.
AB  - This study investigated whether individuals with Williams syndrome (WS) can
      attain a functional level of basic reading skills. The Study also investigated
      broader cognitive factors associated with reading ability in individuals with WS.
      Thirty individuals with WS participated in this study (mean chronological age 21
      years and mean mental age 7 years 7 months). The results supported our hypotheses
      that: firstly, reading abilities would be heterogeneous in WS; secondly, at least
      some WS individuals are capable of achieving a functional basic reading level;
      and thirdly, on average, WS individuals would find reading of nonwords more
      difficult than reading of regular and irregular words. Moreover, higher reading
      ability was found to be associated with increased outcomes in adaptive
      functioning, in particular, Written and Expressive Communication skills and
      Community Living skills, highlighting the potential benefits of developing
      reading abilities in WS. Although Intelligence Quotient (IQ) was related to
      overall basic reading ability generally, it was not found to be a determining
      factor in reading subtypes. Several cognitive skills known to be related to
      reading ability in typically developing individuals were found to be associated
      with reading performance and reading subtypes. Implications for appropriate
      reading instruction are discussed.

PMID- 29601226
TI  - Persons' various experiences of learning processes in patient education for
      osteoarthritis, a qualitative phenomenographic approach.
AB  - BACKGROUND: Patient education (PE) is a core treatment of osteoarthritis (OA)
      with the aim to increase persons' knowledge, self-efficacy, and empowerment.
      OBJECTIVE: To describe person's various experiences of learning processes in PE
      for OA. DESIGN: Phenomenography. METHOD: Semi-structured interviews were
      performed with the same persons, pre- (11) and post- (9) education. RESULTS:
      Various experiences on learning processes were found and were described in an
      outcome space. Achieving knowledge describes self-regulated learning and strongly
      relates to Control, which describes a high order cognitive learning skill, and
      minor to Confirm, which describes a cognitive learning skill based on recognition
      and application. Receiving knowledge describes the expectancy of learning
      regulated from the educator and strongly relates to Comply, which describes a low
      order cognitive learning skill, and minor to Confirm. CONCLUSION: Different
      experiences of motivation and learning impact on persons' learning processes
      which, in turn, influence the persons' capability to accomplish self-efficacy and
      empowerment. The outcome space may serve as a basis for discussions between
      healthcare educators involved in PE to better understand what learning implies
      and to develop PE further.

PMID- 29601227
TI  - The use of pain neuroscience education in older adults with chronic back and/or
      lower extremity pain.
AB  - INTRODUCTION: Chronic pain due to musculoskeletal disorders is the leading cause
      of disability among older adults and is associated with a lower quality of life,
      reduced function, and increased risk of institutionalization. Pain Neuroscience
      Education (PNE) has demonstrated effectiveness in reducing pain and improving
      pain self-efficacy in individuals under 60 years of age, but there is a paucity
      of research examining its use with older adults. If PNE has similar effects in
      older adults, it has the potential to be a useful non-pharmacological
      intervention for this population. METHODS: This quasi-experimental feasibility
      study included 25 subjects over the age of 65 with a 3 month or greater history
      of lower back and/or lower extremity pain. Subjects participated in two semi
      standardized one-on-one PNE sessions and were asked to read a booklet (Why Do I
      Hurt, Louw, International Spine and Pain Institute, USA) in between sessions.
      Subjects' perception of PNE was measured after the second session and gait speed,
      pain disability, and fear of movement were measured pre- and post-PNE. RESULTS:
      Subjects consistently reported a positive experience with PNE. There were
      statically significant positive improvements in gait speed, pain disability, and
      fear of movement after the intervention. CONCLUSION: PNE is a feasible and
      potentially efficacious treatment for older adults with chronic pain.

PMID- 29601228
TI  - Evaluation of three measures of cardiorespiratory fitness in independently
      ambulant stroke survivors.
AB  - Measuring cardiorespiratory fitness (CRF) in the stroke population is
      challenging. Currently, the recommended method is a graded exercise test (GXT) on
      an ergometer such as a treadmill or cycle, which may not always be possible. We
      investigated whether walking tests such as the six-minute walk test (6MWT) and
      the shuttle walk test (SWT) may be appropriate indicators of CRF in the stroke
      population. Twenty-three independently ambulant stroke survivors (11 men, age
      61.5 +/- 18.4 years) within one-year post stroke performed the 6MWT, SWT, and
      cycle GXT, during which peak oxygen consumption (VO2peak) and heart rate (HRpeak)
      were recorded. There were no differences (p > 0.05) in mean VO2peak among the
      three tests (min-max: 17.08-18.09 mL kg-1 min-1). For individuals, small
      discrepancies in VO2peak between the 6MWT and other tests were greater with
      higher fitness levels. HRpeak was significantly (p = 0.005) lower during the
      6MWT. Correlations between VO2peak and performance measures within each test were
      high (6MWT VO2peak and distance: r = 0.78, SWT VO2peak and shuttles: r = 0.73,
      cycle GXT VO2peak and workload: r = 0.77) suggesting the performance measures may
      be clinically useful as proxy measures of CRF. Common comorbidities, such as
      lower-limb joint pain and poor balance, and participant's fastest walking speed,
      should inform the choice of CRF test.

PMID- 29601229
TI  - Immunolocalization of Surfactant Proteins SP-A, SP-B, SP-C, and SP-D in Infantile
      Labial Glands and Mucosa.
AB  - Surfactant proteins in different glandular structures of the oral cavity display
      antimicrobial activity for protection of invading microorganisms. Moreover, they
      are involved in lowering liquid tension in fluids and facilitate secretion flows.
      Numerous investigations for studying the occurrence of surfactant proteins in
      glandular tissues were performed using different methods. In the oral cavity,
      minor salivary glands secrete saliva continuously for the maintenance of a
      healthy oral environment. For the first time, we could show that infantile labial
      glands show expression of the surfactant proteins (SP) SP-A, SP-B, SP-C, and SP-D
      in acinar cells and the duct system in different intensities. The stratified
      squamous epithelium of the oral mucosa revealed positive staining for SPs in
      various cell layers.

PMID- 29601230
TI  - Test-retest reliability, validation, and "minimal detectable change" scores for
      frequently reported tests of objective physical function in patients with non
      dialysis chronic kidney disease.
AB  - Physical function is an important outcome in chronic kidney disease (CKD). We
      aimed to establish the reliability, validity, and the "minimal detectable change"
      (MDC) of several common tests used in renal rehabilitation and research. In a
      repeated measures design, 41 patients with CKD not requiring dialysis (stage 3b
      to 5) were assessed at an interval of 6 weeks. The tests were the incremental
      shuttle walk test (ISWT), "sit-to-stand" (STS) test, estimated 1 repetition
      maximum for quadriceps strength (e1RM), and VO2peak by cardiopulmonary exercise
      testing (CPET). Reliability was assessed using intraclass correlation coefficient
      and Bland-Altman analysis, and absolute reliability by standard error of
      measurement and MDC. The ISWT, STS-60, e1RM, and CPET had "good" to "excellent"
      reliability (0.973, 0.927, 0.927, and 0.866), respectively. STS-5 reliability was
      poor (0.676). The MDC is ISWT, 20 m; STS-5, 7.5 s; STS-60, 4 reps; e1RM, 6.4 kg;
      VO2peak, 2.8 ml/kg/min. There was strong correlation between the ISWT and VO2peak
      (r = 0.73 and 0.74). While there was poor correlation between the STS-5 and e1RM
      (r = 0.14 and 0.47), better correlation was seen between STS-5 and ISWT (r = 0.55
      and 0.74). In conclusion, the ISWT, STS-60, e1RM, and CPET are reliable tests of
      function in CKD. The ISWT is a valid means of exercise capacity. The MDC can help
      researchers and rehabilitation professionals interpret changes following an
      intervention.

PMID- 29601231
TI  - Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by
      Regulating Cell Junctions and ROS Generation in Rats.
AB  - PURPOSE: Choroidal neovascularization (CNV) is a common vision-threatening
      complication associated with many  fundus diseases. The retinal pigment
      epithelial (RPE) cell junction barrier has critical functions in preventing CNV,
      and oxidative stress can cause compromise of barrier integrity and induce
      angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in
      regulating endothelial and epithelial cell junctions. In this work, we explored
      the function and mechanism of Rap1 in CNV in vivo. METHODS: A laser-induced rat
      CNV model was developed. Rap1 was activated through intravitreal injection of the
      Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV
      size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate
      dextran staining. Expression of vascular endothelial growth factor (VEGF) and
      cell junction proteins in RPE/choroid tissues were analyzed by western blots and
      quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells
      were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant
      apocynin was intraperitoneally injected into rats. RESULTS: Activating Rap1 by
      8CPT significantly reduced CNV size and VEGF expression in the rat CNV model.
      Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight
      junction proteins in the RPE barrier. In addition, reducing ROS generation by
      injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1
      activation reduced ROS generation and expression of NADPH oxidase 4. CONCLUSIONS:
      Rap1 activation inhibits CNV through regulating barrier integrity and ROS
      generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce
      vision loss from CNV.

PMID- 29601232
TI  - Aging and exercise: Perceptions of the active lived-body.
AB  - Exploring older people's evocation of their positive experiences of aging has
      been proposed as a counterweight to the Western stereotype of aging as a process
      of decline. The aim of this article is to explore how aging women, who
      participate regularly in group exercise classes, perceive their own bodies and
      the bodies of others. This article reports on the findings from interviews with
      16 women between the age of 70 and 85. We analyzed the data using qualitative
      content analysis. Two overarching and interrelated themes concerning body
      perception emerged from the interviews: "The aging body and appearance" and "The
      body as subject and object." The binary discourse of old age, as either a decline
      or a success appears in our findings. The training contributes to a sense of well
      being experienced through perceived increased physical abilities, self- image and
      self-esteem. Physical ability was perceived as being more important than
      appearance by the participants in this study, considering their preconception of
      an association between declining health, abilities, and older age. Involvement in
      physical activity appears to play a significant role in the perception of the
      women's own aging. Although physical attractiveness is a desirable outcome, the
      most important positive impact of the group exercise was related to increased
      social belonging and well-being, physical abilities, and capabilities. Thus
      implications for practice suggests that an intensive group training contributes
      to the opinion that an aging body is not necessarily a barrier to positive and
      successful aging.

PMID- 29601233
TI  - Comparison of Concussion Rates Between NCAA Division I and Division III Men's and
      Women's Ice Hockey Players: Letter to the Editor.

PMID- 29601234
TI  - Is Treatment of Segond Fracture Necessary With Combined Anterior Cruciate
      Ligament Reconstruction? Response.

PMID- 29601235
TI  - Is Treatment of Segond Fracture Necessary With Combined Anterior Cruciate
      Ligament Reconstruction? Response.

PMID- 29601236
TI  - Comparison of Concussion Rates Between NCAA Division I and Division III Men's and
      Women's Ice Hockey Players: Response.

PMID- 29601237
TI  - Segond Fractures Are Not a Risk Factor for Anterior Cruciate Ligament
      Reconstruction Failure: Response.

PMID- 29601238
TI  - Arthroscopic Versus Open Latarjet in the Treatment of Recurrent Anterior Shoulder
      Dislocation With Marked Glenoid Bone Loss: A Prospective Comparative Study:
      Letter to the Editor.

PMID- 29601240
TI  - Meta-analysis of the Risk of Infections After Anterior Cruciate Ligament
      Reconstruction by Graft Type: Letter to Editor.

PMID- 29601241
TI  - Meta-analysis of the Risk of Infections After Anterior Cruciate Ligament
      Reconstruction by Graft Type: Response.

PMID- 29601242
TI  - The Non-Latarjet.

PMID- 29601243
TI  - Arthroscopic Versus Open Latarjet in the Treatment of Recurrent Anterior Shoulder
      Dislocation With Marked Glenoid Bone Loss: A Prospective Comparative Study:
      Response.

PMID- 29601244
TI  - Segond Fractures Are Not a Risk Factor for Anterior Cruciate Ligament
      Reconstruction Failure: Letter to the Editor.

PMID- 29601245
TI  - Is Treatment of Segond Fracture Necessary With Combined Anterior Cruciate
      Ligament Reconstruction? Letter to the Editor.

PMID- 29601246
TI  - Is Treatment of Segond Fracture Necessary With Combined Anterior Cruciate
      Ligament Reconstruction? Letter to the Editor.

PMID- 29601247
TI  - An update on treatment for post-menopausal metastatic breast cancer in elderly
      patients.
AB  - INTRODUCTION: Elderly patients make up a significant proportion of patients with
      metastatic breast cancer. With several options available in the metastatic
      setting for hormone positive breast cancer, these patients require an
      individualized approach to decision-making that considers multiple factors beyond
      performance status and chronologic age. Areas covered: The authors review the
      literature on endocrine monotherapy and combinations for hormone positive
      metastatic breast cancer, with specific commentary on the efficacy and toxicity
      for elderly patients. The authors describe the role of comprehensive geriatric
      assessment (CGA) and highlight the considerations for the use of bone modifying
      agents, and HER2-targeted therapy for hormone positive/HER2+ patients. Expert
      opinion: Evidence for elderly patients is largely based on subgroup analyses,
      which should be interpreted with caution. Nonetheless, elderly patients with
      metastatic hormone receptor positive breast cancer appear to derive similar
      benefit from treatments as younger patients. Similarly, for most drugs, these
      patients have no significant worsening of toxicity compared to younger patients.
      In addition to tumor biology, patient values and information from the CGA should
      be used to guide treatment decisions.

PMID- 29601248
TI  - Commentary on "Vitamin D and the Breastfeeding Infant: Family Medicine
      Clinicians' Knowledge, Attitudes, and Practices" by Oberhelman et al.

PMID- 29601249
TI  - Breastfeeding in the Community: Sharing Stories on Implementations That Work.

PMID- 29601250
TI  - Examining Trends in Cost and Clinical Benefit of Novel Anticancer Drugs Over
      Time.
AB  - PURPOSE: The purpose of this study was to determine if clinical benefits of novel
      anticancer drugs, measured by the ASCO Value Framework and European Society of
      Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale, have increased over
      time in parallel with increasing costs. METHODS: Anticancer drugs from phase III
      randomized controlled trials cited for clinical efficacy evidence in drug
      approvals between January 2006 to December 2015 were identified and scored using
      both frameworks. For each drug, the monthly price and incremental anticancer drug
      costs were calculated. Relationships between cost and year of approval were
      examined using generalized linear regressions models. Ordinary least square
      models were used to evaluate relationships between ASCO and ESMO scores and year
      of approval. Spearman correlation coefficients between costs and clinical benefit
      scores were calculated. RESULTS: In total, 42 randomized controlled trials were
      included. Both monthly prices and incremental anticancer drug costs were
      significantly associated with year of approval and showed an average annual
      increase of 9% and 21%, respectively. The predicted mean incremental anticancer
      drug cost increased from $30,447 in 2006 to $161,141 in 2015 (greater than five
      fold increase). Both ASCO and ESMO scores were not statistically associated with
      year of approval or correlated with monthly prices or incremental anticancer drug
      costs. CONCLUSION: Over the past decade, costs of novel oncology drugs have
      increased, while clinical benefits of these medications have not experienced a
      proportional positive change. The incremental anticancer drug costs have
      increased at a much greater rate than monthly prices, indicating that the
      increase in anticancer drug costs may be higher than commonly reported.

PMID- 29601251
TI  - The effect of a wearable soft-robotic glove on motor function and functional
      performance of older adults.
AB  - Reduced grip strength, resulting in difficulties in performing daily activities,
      is a common problem in the population of older adults. Newly developed soft
      robotic devices have the potential to support older adults with reduced grip in
      daily activities. The objective of this study was to evaluate the direct,
      assistive effect of grip support from the wearable, soft-robotic ironHand glove.
      In total, 65 older adults with self-reported decline of hand function resulting
      from various disorders participated in this cross-sectional study. They performed
      various hand function tests with and without the glove during a single session.
      At the end, usability was scored. Participants were able to produce more pinch
      strength with the glove compared to without glove (p <= 0.001) and usability was
      rated very positively. However, this was not reflected in improved functional
      performance with the glove, as measured with timed tasks (p < 0.001).
      Furthermore, no correlation was found between baseline handgrip strength and
      changes in performance (between without and with glove) of all assessments (rho
      <= 0.137, p >= 0.288). Further design adaptations are desired and more research
      is needed to investigate if performance with the glove can improve, when taking
      quality of task performance into account, or when applying a longer acquaintance
      period with the glove.

PMID- 29601252
TI  - Chemical Contaminants in Raw and Pasteurized Human Milk.
AB  - BACKGROUND: Environmental contaminants ranging from legacy chemicals like p,p'
      dichlorodiphenyltrichloroethane (DDT) to emerging chemicals like phthalates are
      ubiquitous. Research aims/questions: This research aims to examine the presence
      and co-occurrence of contaminants in human milk and effects of pasteurization on
      human milk chemical contaminants. METHODS: We analyzed human milk donated by 21
      women to a milk bank for 23 chemicals, including the persistent organic
      pollutants (POPs) polychlorinated biphenyls (PCBs), polybrominated diphenyl
      ethers (PBDEs), dichlorodiphenyltrichloroethane (DDT), and
      dichlorodiphenyldichloroethylene (DDE) isomers that are known to sequester in
      adipose tissue, along with the current-use and nonpersistent pesticides
      chlorpyrifos and permethrin, phthalates, and bisphenol A (BPA). Human milk was
      analyzed raw and pasteurized for these chemicals using gas chromatography-tandem
      mass spectrometry for the POPs and high-performance liquid chromatography-tandem
      mass spectrometry for non-POPs. RESULTS: Within the different chemical classes,
      PBDE47, PCB153, ppDDE, and MEHHP (phthalate metabolite) had the highest median
      concentrations and were observed in all samples. We also observed chlorpyrifos
      and BPA in all samples and permethrin in 90% of the samples tested. Only two
      chemicals, chlorpyrifos and permethrin, were susceptible to substantial
      degradation from pasteurization, a standard method for processing donated human
      milk. CONCLUSION: We detected 19 of 23 chemicals in all of our prepasteurized
      milk and 18 of 23 chemicals in all of our pasteurized milk. Pasteurization did
      not affect the presence of most of the chemicals. Future research should continue
      to explore human milk for potential chemical contamination and as a means to
      surveil exposures among women and children.

PMID- 29601254
TI  - Identification of a new type tadalafil analogue in a supplement product.
AB  - A novel compound structurally similar to tadalafil was found in a dietary
      supplement by adulterants screening test and isolated by column chromatography.
      After analysis by accurate mass, nuclear magnetic resonance (NMR) and X-ray, the
      structure of this novel tadalafil analogue was determined as (5R, 16R)-5-(1,3
      benzodioxol-5-yl)-2- (3-ethypentan-3-yl)-15,16-dihydro(1H-imidazo[1,5
      a]pyrido)[3,4-b]indol-1,3-dion.

PMID- 29601255
TI  - Tinnitus.

PMID- 29601256
TI  - Four-year antibody persistence and response to a booster dose of a pentavalent
      MenABCWY vaccine administered to healthy adolescents and young adults.
AB  - This open-label, multicenter extension study (NCT02451514) assessed persistence
      of Neisseria meningitidis serogroups ABCWY antibodies 4 years after primary
      vaccination. Adolescents and young adults who previously received 2 doses of
      MenABCWY+OMV (Group III), 1 dose of MenACWY-CRM (Group VI), or newly-recruited
      vaccine-naive participants (Group VII) were administered 1 (Group III) or 2 doses
      (Groups VI and VII) of MenABCWY+OMV, 1 month apart. Immunogenicity was assessed
      by human serum bactericidal assay (hSBA). Safety and reactogenicity were also
      evaluated. Percentages of participants with hSBA titers >=8 (serogroups ACWY),
      >=5 (serogroup B) and hSBA geometric mean titers (GMTs) were evaluated in all 129
      enrolled participants (Group III: 33; Group VI: 46; Group VII: 50). Anti-ACWY
      antibody concentrations waned over 4 years post-vaccination, but remained above
      pre-vaccination concentrations. Similarly, levels of antibodies against serogroup
      B test strains also waned over 4 years post-vaccination, but remained above pre
      vaccination concentrations for some strains. MenABCWY+OMV booster induced a
      robust anamnestic anti-ACWY response in Group III and VI and a good response
      against serogroup B test strains (>=82%) in Group III. In serogroup B-naive
      participants (Groups VI and VII), anti-B responses to 2 doses of MenABCWY+OMV
      were less homogenous and lower than in Group III. MenABCWY+OMV was reactogenic,
      but well-tolerated. No safety concerns were identified. These findings indicate
      that although antibodies against N. meningitidis serogroups ABCWY waned over 4
      years post-vaccination, exposure to a MenABCWY+OMV booster dose elicits an
      anamnestic response in adolescents previously exposed to the same or another
      multivalent meningococcal vaccine.

PMID- 29601253
TI  - The current status, challenges, and future developments of new tuberculosis
      vaccines.
AB  - Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10
      causes of death worldwide. TB results in more fatalities than multi-drug
      resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the
      prevention and control of infectious diseases. Unfortunately, the only licensed
      preventive vaccine against TB, bacilli Calmette-Guerin (BCG), is ineffective for
      prevention of pulmonary TB in adults. Therefore, it is very important to develop
      novel vaccines for TB prevention and control. This literature review provides an
      overview of the innate and adaptive immune response during M. tuberculosis
      infection, and presents current developments and challenges to novel TB vaccines.
      A comprehensive understanding of vaccines in preclinical and clinical studies
      provides extensive insight for the development of safer and more efficient
      vaccines, and may inspire new ideas for TB prevention and treatment.

PMID- 29601257
TI  - A CRISPR Way to Restore Hearing.

PMID- 29601258
TI  - Fast simultaneous determination of capsaicin, dihydrocapsaicin and nonivamide for
      detecting adulteration in edible and crude vegetable oils by UPLC-MS/MS.
AB  - Capsaicinoids are pungent components in hot peppers, which have been detected in
      waste cooking oil. However, trace analysis of capsaicinoids in edible and crude
      vegetable oils is a challenging task due to the complex matrix. In this study, a
      simple liquid-liquid extraction and solid phase extraction (SPE) coupled with RP
      UPLC-ESI-MS/MS method was developed for the quantification of capsaicinoids in
      edible and crude vegetable oils to screen the adulteration with waste cooking
      oil. This method was used to simultaneously determine 3 capsaicinoids (capsaicin,
      dihydrocapsaicin, and nordihydrocapsaicin) with capsaicin-d3, and
      dihydrocapsaicin-d3 as internal standards. This method allows the complete
      analysis of a sample in only an hour, even including sample preparation and
      chromatographic separation. The linear range of 3 capsaicinoids ranged between
      0.5 and 40 ug/kg. The limit of detection (LOD) and limit of quantification (LOQ)
      for capsaicinoids were calculated as 0.15 and 0.5 ug/kg, respectively.
      Quantitative recoveries ranging from 92.9% to 105% were obtained by the analysis
      of spiked oil. The relative standard deviations were less than 5% (n = 6). The
      established method can potentially overcome the interference of triacylglycerols
      and fatty acids in edible and crude vegetable oils, and have been successfully
      applied to analyse real oil samples. This method provided a rapid and reliable
      method for the detection of adulteration of vegetable oils with waste cooking
      oils.

PMID- 29601259
TI  - Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus
      vaccine (sIPV).
AB  - Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live
      attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV)
      has played a vital role in reducing economic burden of poliomyelitis and
      maintaining appropriate antibody levels in the population. However, due to its
      high cost and limited manufacturing capacity, sIPV cannot reach its full
      potential for global poliovirus eradication in developing countries. Therefore,
      to address this situation, we designed this study to evaluate the dose-sparing
      effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and
      polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results
      showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with
      BW006 provides a seroconversion rate similar to that of full-dose sIPV without
      adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without
      adjuvant after the first immunization. The combination of AS03 or AS03 with BW006
      as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both
      humoral and cellular immune responses. Therefore, our study revealed that the
      combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV
      development.

PMID- 29601260
TI  - Sensitive enzyme immunoassay for screening methandienone in dietary supplements.
AB  - Methandienone is a synthetic exogenous steroid which, like other anabolic
      steroids, is strictly regulated in many countries. In recent years, increasing
      numbers have been detected of illegal additions into dietary supplements of
      methandienone and other anabolic androgenic steroids (AAS). In this work, a
      competitive indirect enzyme-linked immunosorbent assay (ELISA) has been
      constructed for the detection of methandienone using an antiserum against
      methandienone. Under optimal experimental conditions, the ELISA achieved a limit
      of detection of 0.04 +/- 0.01 ug.g-1. The obtained intra- and inter-day
      coefficients of variation were less than 8%. The developed ELISA was applied in
      the analysis of real dietary supplement samples. To minimise the effect of the
      sample matrix, the sample extracts were simply diluted before addition into the
      immunoassay. The achieved recovery values were around 100%. Results obtained from
      the ELISA correlated well, both in terms of accuracy and precision, with those
      obtained by UHPLC-MS/MS (reference method). The presented ELISA could be
      successfully applied for the simple screening of dietary supplements.

PMID- 29601262
TI  - Appendiceal Pinworms.

PMID- 29601261
TI  - EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease.

PMID- 29601263
TI  - Hepatitis C in Injection-Drug Users - A Hidden Danger of the Opioid Epidemic.

PMID- 29601264
TI  - Associations Between Nonnutritive Sweetener Intake and Metabolic Syndrome in
      Adults.
AB  - OBJECTIVE: Individuals looking to improve their health or weight status often use
      nonnutritive sweeteners (NNS), yet NNS consumption has been associated with
      increased risk factors for metabolic syndrome (MetS). Most studies examining NNS
      only assess total intake using diet soda as a proxy for NNS consumption, without
      distinguishing potential risks associated with individual sweeteners. The
      objective of this cross-sectional investigation was to identify whether there
      were associations between NNS consumption (total or individual) and risk factors
      for MetS in adults (n = 125) from Southwest Virginia. METHODS: Participants
      provided three 24-hour dietary recalls and blood pressure, waist circumference,
      fasting glucose, triglycerides, and high-density lipoprotein cholesterol were
      assessed. Linear regression models, adjusted for age, sex, caloric intake,
      dietary quality, and physical activity, examined associations between total and
      individual types of NNS with MetS and MetS risk factors. RESULTS: Sixty-three
      participants were classified as NNS consumers and eighteen met the criteria for
      MetS. While no significant associations between MetS and NNS consumption were
      found, waist circumference was positively associated with total NNS, saccharin,
      sucralose, and acesulfame potassium, and both fasting glucose and triglyceride
      values were positively associated with total NNS and aspartame consumption.
      CONCLUSION: While these cross-sectional data are consistent with previous work
      implicating NNS in development of MetS, additional research using randomized
      controlled trials is needed to clarify whether and how NNS in general or specific
      NNS might contribute to risk factors for MetS. This trial was registered at
      clinicaltrials.gov (NCT03364452).

PMID- 29601265
TI  - Coronary Artery Fistulas: Pathophysiology, Imaging Findings, and Management.
AB  - Coronary artery fistulas (CAFs) are abnormal communications of coronary arteries
      whereby venous circuits bypass the normal capillaries within the myocardium. CAFs
      are rare, and most affected patients are asymptomatic. However, these fistulas
      are the most common coronary artery anomalies that can alter coronary hemodynamic
      parameters. Although most CAFs are asymptomatic in young patients, symptoms and
      complications become more frequent with increasing age. CAFs are characterized by
      variable clinical manifestations that are based on the size, origin, and drainage
      site of the fistula. In symptomatic cases, surgical ligation or percutaneous
      transcatheter closure is often recommended. Although CAFs historically have been
      evaluated with conventional invasive angiography, electrocardiographically gated
      cardiac computed tomographic (CT) angiography has emerged as the noninvasive
      alternative modality of choice owing to the high spatial and temporal resolution
      and short acquisition time. Furthermore, three-dimensional volume-rendered CT
      angiograms facilitate accurate assessment of the complex anatomy of CAFs,
      including their origin, drainage site, and complexity and the number and size of
      fistulous tracts. Knowledge of these characteristics is crucial for therapeutic
      planning. Radiologists must be aware of the pathophysiology, clinical
      manifestations, and characteristic CT angiographic findings of CAFs; appropriate
      CT angiographic protocols for evaluation of various CAFs; and the role of CT
      angiography in preprocedural planning and follow-up. Online supplemental material
      is available for this article. (c)RSNA, 2018.

PMID- 29601266
TI  - Tumors in von Hippel-Lindau Syndrome: From Head to Toe-Comprehensive State-of-the
      Art Review.
AB  - Von Hippel-Lindau syndrome (VHL) is an autosomal-dominant hereditary tumor
      disease that arises owing to germline mutations in the VHL gene, located on the
      short arm of chromosome 3. Patients with VHL may develop multiple benign and
      malignant tumors involving various organ systems, including retinal
      hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac
      tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic
      cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas,
      paragangliomas, and epididymal and broad ligament cystadenomas. The VHL/hypoxia
      inducible factor pathway is believed to play a key role in the pathogenesis of
      VHL-related tumors. The diagnosis of VHL can be made clinically when the
      characteristic clinical history and findings have manifested, such as the
      presence of two or more CNS HBs. Genetic testing for heterozygous germline VHL
      mutation may also be used to confirm the diagnosis of VHL. Imaging plays an
      important role in the diagnosis and surveillance of patients with VHL.
      Familiarity with the clinical and imaging manifestations of the various VHL
      related tumors is important for early detection and guiding appropriate
      management. The purpose of this article is to discuss the molecular cytogenetics
      and clinical manifestations of VHL, review the characteristic multimodality
      imaging features of the various VHL-related tumors affecting multiple organ
      systems, and discuss the latest advances in management of VHL, including current
      recommendations for surveillance and screening. (c)RSNA, 2018 An earlier
      incorrect version of this article appeared online. This article was corrected on
      April 9, 2018.

PMID- 29601267
TI  - Performance of purified grape pomace as a fining agent to reduce the levels of
      some contaminants from wine.
AB  - The quality of red wine depends on the absence of compounds which may affect its
      safety and/or stability such as ochratoxin A, biogenic amines and some metals and
      trace compounds. The presence of ochratoxin A in musts and wines is due to fungal
      contamination of the grapes and has been classified as a possible human
      carcinogen. Biogenic amines are formed by the microbiological decarboxylation of
      the corresponding amino acid precursors during the fermentation or ageing and
      storage, and, at high concentrations, they may induce adverse reactions in
      sensitive people. Trace elements may have both a nutritional and a toxic effect
      on health, but also can cause turbidity and stability problems. Their presence is
      affected mainly by natural factors such as soil mineral content and direct
      contact with tank surfaces and metallic tubing during winemaking. One of the best
      options to remove these compounds when present in excess in wine is fining.
      However, some fining agents commonly used may themselves present problems related
      with their allergenic properties or with their propensity to increase the protein
      content, which can cause turbidity problems. In an attempt to avoid such these
      problems, purified grape pomace was tested as a fining alternative since it has
      been seen to have a high capacity to reduce the astringency, turbidity and also
      the ochratoxin A content. The main aim of this work, therefore, was to study if
      this material can limit the presence of ochratoxin A, biogenic amines and metals
      and some trace elements in a Monastrell red wine, thus increasing the value and
      safety of this product.

PMID- 29601268
TI  - Influence of a Concurrent Exercise Training Program During Pregnancy on Colostrum
      and Mature Human Milk Inflammatory Markers: Findings From the GESTAFIT Project.
AB  - BACKGROUND: Although exercise reduces systemic inflammation, information
      regarding its influence on human milk is scarce or inexistent. Research Aim: The
      aim of this study was to investigate the influence of an exercise intervention
      during pregnancy on colostrum and mature human milk inflammatory markers.
      METHODS: The authors conducted a pseudorandomized controlled trial. The exercise
      group followed a concurrent aerobic and strength training, three 60-minutes
      sessions per week, from the 17th gestational week until delivery. For the
      specific aims of this study, only women able to produce enough milk were included
      for data analyses, resulting in 24 exercise and 23 control women. Colostrum and
      mature human milk proinflammatory and anti-inflammatory cytokines (fractalkine,
      interleukin [IL]-1beta, IL-6, IL-8, IL-10, interferon [IFN]-gamma, and tumor
      necrosis factor [TNF]-alpha) were measured using Luminex xMAP technology.
      RESULTS: The mothers who followed the exercise program had 36% lower IL-8 and 27%
      lower TNF-alpha concentrations in their colostrum than those in the control group
      ( p < .05 and p < .01, respectively). The colostrum from mothers who followed the
      exercise program also presented borderline significant 22% lower IL-6 ( p <
      .100). The mature milk from mothers who followed the exercise program had 30%
      greater fractalkine ( p = .05) and borderline significant 20% higher IL-10 ( p =
      .100). The exercise intervention did not affect IFN-gamma concentrations.
      CONCLUSIONS: This concurrent exercise program promoted a less proinflammatory
      profile in human milk, especially in colostrum. Moreover, it might increase
      mature human milk fractalkine, which could induce a greater neurodevelopment and
      neuroprotection in the newborn. This trial was registered at ClinicalTrials.gov
      (NCT02582567) on October 20, 2015.

PMID- 29601270
TI  - Do Fitness Apps Need Text Reminders? An Experiment Testing Goal-Setting Text
      Message Reminders to Promote Self-Monitoring.
AB  - Fitness tracking apps have the potential to change unhealthy lifestyles, but
      users' lack of compliance is an issue. The current intervention examined the
      effectiveness of using goal-setting theory-based text message reminders to
      promote tracking activities on fitness apps. We conducted a 2-week experiment
      with pre- and post-tests with young adults (n = 50). Participants were randomly
      assigned to two groups-a goal-setting text message reminder group and a generic
      text message reminder group. Participants were asked to use a fitness tracking
      app to log physical activity and diet for the duration of the study. Participants
      who received goal-setting reminders logged significantly more physical activities
      than those who only received generic reminders. Further, participants who
      received goal-setting reminders liked the messages and showed significantly
      increased self-efficacy, awareness of personal goals, motivation, and intention
      to use the app. The study shows that incorporating goal-setting theory-based text
      message reminders can be useful to boost user compliance with self-monitoring
      fitness apps by reinforcing users' personal goals and enhancing cognitive factors
      associated with health behavior change.

PMID- 29601269
TI  - Molecular Minimal Residual Disease in Acute Myeloid Leukemia.
AB  - BACKGROUND: Patients with acute myeloid leukemia (AML) often reach complete
      remission, but relapse rates remain high. Next-generation sequencing enables the
      detection of molecular minimal residual disease in virtually every patient, but
      its clinical value for the prediction of relapse has yet to be established.
      METHODS: We conducted a study involving patients 18 to 65 years of age who had
      newly diagnosed AML. Targeted next-generation sequencing was carried out at
      diagnosis and after induction therapy (during complete remission). End points
      were 4-year rates of relapse, relapse-free survival, and overall survival.
      RESULTS: At least one mutation was detected in 430 out of 482 patients (89.2%).
      Mutations persisted in 51.4% of those patients during complete remission and were
      present at various allele frequencies (range, 0.02 to 47%). The detection of
      persistent DTA mutations (i.e., mutations in DNMT3A, TET2, and ASXL1), which are
      often present in persons with age-related clonal hematopoiesis, was not
      correlated with an increased relapse rate. After the exclusion of persistent DTA
      mutations, the detection of molecular minimal residual disease was associated
      with a significantly higher relapse rate than no detection (55.4% vs. 31.9%;
      hazard ratio, 2.14; P<0.001), as well as with lower rates of relapse-free
      survival (36.6% vs. 58.1%; hazard ratio for relapse or death, 1.92; P<0.001) and
      overall survival (41.9% vs. 66.1%; hazard ratio for death, 2.06; P<0.001).
      Multivariate analysis confirmed that the persistence of non-DTA mutations during
      complete remission conferred significant independent prognostic value with
      respect to the rates of relapse (hazard ratio, 1.89; P<0.001), relapse-free
      survival (hazard ratio for relapse or death, 1.64; P=0.001), and overall survival
      (hazard ratio for death, 1.64; P=0.003). A comparison of sequencing with flow
      cytometry for the detection of residual disease showed that sequencing had
      significant additive prognostic value. CONCLUSIONS: Among patients with AML, the
      detection of molecular minimal residual disease during complete remission had
      significant independent prognostic value with respect to relapse and survival
      rates, but the detection of persistent mutations that are associated with clonal
      hematopoiesis did not have such prognostic value within a 4-year time frame.
      (Funded by the Queen Wilhelmina Fund Foundation of the Dutch Cancer Society and
      others.).

PMID- 29601271
TI  - The Importance of 'Likes': The Interplay of Message Framing, Source, and Social
      Endorsement on Credibility Perceptions of Health Information on Facebook.
AB  - Online sources not only permeate the information-seeking environment of the
      younger generation, but also have profound influence in shaping their beliefs and
      behaviors. In this landscape, examining the factors responsible for credibility
      perceptions of online information is fundamental, particularly for health-related
      information. Using a 2 (frames: gain vs. loss) * 2 (source: expert vs. non
      expert) * 2 (social endorsement: high vs. low) randomized between-subjects
      experimental design, this study examines the effect of health message framing and
      the moderating effects of social endorsement and source type on credibility
      perceptions of Facebook posts. Testing across two issues--physical activity and
      alcohol consumption--findings indicate that the gain-framed message was perceived
      as most credible. Additionally, significant three-way interactions suggest that
      social endorsement and source type affect the relationship between message
      framing and credibility perceptions. Specifically, the findings demonstrate that
      a gain-framed message from an expert source with high number of 'likes' is
      considered the most credible message. These findings have significant
      implications for information gathering from social media sources, such as the
      influence of 'likes' on health information.

PMID- 29601272
TI  - Unhealthy weight control behaviors among youth: Sex of sexual partner is linked
      to important differences.
AB  - Unhealthy weight control behaviors (UWCBs) have been decreasing for most youth
      over time, yet little is known whether these behaviors have changed for sexual
      minority (e.g., non-heterosexual) youth. This is important because many studies
      have found that sexual minorities report some of the highest rates of UWCBs. To
      determine whether or not these behaviors have changed over time, given the
      extreme changes in social contexts over the past two decades, we utilised three
      waves of the Minnesota Student Survey (N = 55,597, Mage = 17). In doing so, we
      report trends, disparities, and changes in disparities of UWCBs. Overall, the
      prevalence of UWCBs has declined from 1999 to 2010 for all youth, but there are
      alarming disparities by sex of sexual partner. We found that both- and same-sex
      partnered male youth were more likely to fast, use diet pills, and vomit on
      purpose to lose weight compared to their opposite-sex partnered counterparts in
      all three survey years; specifically, both-sex partnered boys were up to 5.5* as
      likely to vomit on purpose compared to their opposite-sex partnered counterparts.
      Likewise, both-sex partnered girls were more likely to use diet pills and vomit
      on purpose to lose weight compared to opposite-sex partnered girls in all three
      survey years. Additionally, the disparity in fasting to lose weight widened for
      the same-sex partnered females compared to the opposite-sex partnered females
      from 1998 to 2004. This has implications for UWCB interventions and preventions
      targeted specifically towards sexual minorities.

PMID- 29601273
TI  - Barriers to Women's Participation: Experiences of Volunteers and Community
      Healthcare Authorities.
AB  - Along with health development in general terms, women's involvement in health
      programs can be effective in raising their self-confidence and their health
      promotion. This study was carried out to unveil the barriers to and challenges of
      the health volunteers and to present the solutions to its promotion using active
      women participants' experiences and the authorities of the program. The study was
      carried out using qualitative method along with content analysis in city of
      Tabriz East-Azerbaijan province, Iran. Data collection was conducted utilizing
      semistructured individual interviews and focus group discussions with the
      participation of 29 health volunteers and responsible authorities. The
      participants were selected using purposive sampling with maximum variation. Data
      analysis implemented conventional content analysis using MAXODA. Barriers to and
      challenges of health volunteers were generally categorized into four main themes
      including volunteers and trainers' inadequate capabilities, inadequate acceptance
      of the volunteers, restrictive social norms, and organizational problems. It
      seems that interaction among health system, people, and health volunteers should
      be improved. Holding training programs about the activities of health volunteers
      at the society level leads into the better utilization of society sources in
      health programs.

PMID- 29601274
TI  - REVISITING THE SAFE PLACE:Method and Regulatory Aspects in Psychotherapy when
      Easing Allostatic Overload in Traumatized Patients.
AB  - Safe-place inductions are considered important altered states of consciousness
      (ASC) to be (re)installed during trauma-informed psychotherapy. Coregulation
      aimed at changing implicit relational knowing and increasing integration and
      coherence through relational work and hypnotic techniques is crucial, as clients'
      abilities to self-soothe and regulate have become seriously impaired. Thus,
      resource-oriented metaphors as inner strength imagery is advocated. Also, methods
      such as creative-arts therapy and neurofeedback will induce ASCs, as most methods
      used with complex traumatized clients, due to their high hypnotizability. When
      positive or soothing imagery or relationally held suggestions for changed
      attentional focus are added to both psychodynamic psychotherapy and CBT, a hetero
      hypnosis will be induced-a prerequisite for phase-specific trauma therapy aimed
      at changing inner schemas and scripts.

PMID- 29601275
TI  - EFFECTS OF CONVERSATIONAL HYPNOSIS ON RELATIVE PARASYMPATHETIC TONE AND PATIENT
      COMFORT DURING AXILLARY BRACHIAL PLEXUS BLOCKS FOR AMBULATORY UPPER LIMB
      SURGERY:A Quasiexperimental Pilot Study.
AB  - This two-center quasiexperimental pilot study was to determine the effect of
      conversational hypnosis on patient comfort and parasympathetic tone, which may
      represent a quantitative measure of hypnotic depth, during regional anesthesia.
      The patients received conversational hypnosis in one center and oral
      premedication in the other. The patients' subjective comfort (0-10 rating scale)
      and objective parasympathetic tone, as assessed by the Analgesia/Nociception
      Index (ANI), were measured before and after regional anesthesia. The
      parasympathetic tone and comfort scores evidenced a significantly greater
      increase in the hypnosis patients than in controls. These findings suggest that
      using conversational hypnosis during regional anesthesia may be followed by a
      subjective increase in patient comfort and an objective increase in
      parasympathetic tone, monitored by ANI.

PMID- 29601276
TI  - THE EFFECT OF A HYPNOTIC-BASED ANIMATED VIDEO ON STRESS AND PAIN REDUCTION IN
      PEDIATRIC SURGERY.
AB  - Presurgical stress and its negative influences on postsurgical recovery and pain
      are well documented in the medical literature. Hence, the reduction of stress is
      advisable. The present study aimed to reduce stress using a hypnotic-based
      animated video. Thirty children aged 3 to 16 years hospitalized for ambulatory
      surgery for undescended testes or umbilical/inguinal hernia were recruited for
      the study. They watched the video 1 time prior to surgery in the presence of
      their parents and reported their anxiety and pain pre- and postvideo watching on
      a visual analogue scale. The results show a statistically significant reduction
      in both anxiety and pain. The article describes the structuring of the animated
      video and includes links to English, Hebrew, and Arabic versions of it.

PMID- 29601278
TI  - The Effect of Hypnosis on Adherence to Antituberculosis Drugs Using the Health
      Belief Model.
AB  - An RCT on the efficacy of hypnosis in improving adherence to antituberculosis
      treatment using the Health Belief Model (HBM). Sixty study subjects were sampled
      at random from tuberculosis patients who visited the Center for Pulmonary
      Community Health in Solo, Indonesia. Hypnotherapy with posthypnotic suggestions
      was delivered once a week over 6 months. The data on pretested 7 HBM constructs
      were analyzed using t test and path analysis. Hypnotherapy had a positive effect
      on perceived susceptibility, seriousness, threat, benefit, and self-efficacy. It
      indirectly had a positive effect on adherence. Hypnotherapy had a negative effect
      on perceived barrier. This study supports the hypothesis that hypnotherapy
      effectively improves adherence to tuberculosis treatment, by enhancing health
      related perception and beliefs in the HBM.

PMID- 29601281
TI  - The feasibility of goal attainment scaling to measure case resolution in elder
      abuse and neglect adult protective services intervention.
AB  - OBJECTIVES: This pilot study describes implementation procedures of goal
      attainment scaling (GAS) and examines the feasibility of using GAS to measure the
      multifarious intervention outcome of case resolution in elder mistreatment (EM)
      adult protective services (APS). METHODS: Substantiated EM victims (n = 27) were
      recruited prospectively from the State of Maine APS. An adapted GAS approach was
      implemented involving development of a pre-populated goal scale menu and web
      based GAS application. RESULTS: The GAS menu comprised 18 goals and corresponding
      scales spanning several domains of case resolution: social support, service
      access, health/functioning, enhancing independence, and protective measures. The
      overall GAS process had mean length 33.8 min per case. The mean GAS summary t
      score (54.3) aligned with theoretical expectations. DISCUSSION: Without a measure
      of case resolution, research cannot compare the effectiveness of different EM
      intervention models. Findings suggest that GAS is a feasible, client-centered
      strategy to measure the multifarious EM intervention case resolution outcome.

PMID- 29601280
TI  - ENHANCING IMPLICIT LEARNING WITH POSTHYPNOTIC SUGGESTION: An ERP Study.
AB  - Can posthypnotic suggestion (PHS) enhance cognitive abilities? The authors tested
      behaviorally and with event-related potentials (ERP) if sequential learning (SL),
      the ability to learn statistical regularities, can be enhanced with PHS. Thirty
      adults were assessed with the Stanford Hypnotic Susceptibility Scale (Form C) and
      an auditory SL task. Before this task, half the sample received a PHS to enhance
      SL, and the other half received the same suggestion under normal waking state.
      Response times and ERPs indicated a strong effect of PHS. Compared to the control
      group, PHS inverted, attenuated, or left unaffected the response time SL effect
      in low, medium, and high hypnotizability participants, respectively. These
      results suggest that PHS cannot be used to enhance SL.

PMID- 29601282
TI  - Risk Assessment of Adolescents with Intellectual Disabilities Who Exhibit Sexual
      Behavior Problems or Sexual Offending Behavior.
AB  - Adolescents with intellectual disabilities are known to engage in various sexual
      behavior problems or sexual offending behaviors. This article provides a review
      of important aspects of risk assessment within the context of a broader, more
      comprehensive and holistic assessment of these individuals. Pertinent risk and
      sexual interest assessment tools are identified along with their strengths and
      limitations. Issues that are often unattended to are addressed, including
      consideration of the behavioral implications of the young person's diagnosis and
      level of cognitive functioning, need for sexual knowledge and sexual interest
      assessment, and issues related to making a mental health diagnosis.
      Recommendations for future research are also offered.

PMID- 29601283
TI  - The mistreatment of older Canadians: findings from the 2015 national prevalence
      study.

PMID- 29601284
TI  - Housing needs of grandparent caregivers: grandparent, youth, and professional
      perspectives.
AB  - This qualitative study examined the housing needs of grandparent caregivers and
      the youth in their care in New York State. Nine focus groups were conducted
      separately with grandparent caregivers (n = 46) and youth (n = 34), and
      interviews were conducted with key informants (n = 17) knowledgeable about
      housing and issues. Housing needs of greatest priority, contextual differences,
      and potential barriers to securing housing and social services were identified.
      Key themes indicated that housing challenges stem from four problem domains: the
      experience of poverty, which creates affordability challenges that trap
      grandparent caregivers and their grandchildren in unsuitable homes and unsafe
      neighborhoods; physical challenges of aging grandparents, which require specific
      housing accommodations; changes in family composition when taking in
      grandchildren, which necessitate moving out of prior accommodations or changing
      housing plans due to regulatory issues; and obstacles to obtaining needed
      benefits, including a lack of information, burdensome application processes,
      ineligibility, and a shortage of resources. These issues are discussed with
      implications for policy and practice.

PMID- 29601286
TI  - Implementing a college mental health program - an overview of the first twelve
      months.
AB  - OBJECTIVE: To evaluate the demographics and clinical utilization patterns among
      college students during the initial 12 months of a novel, multi-disciplinary,
      collaborative, college mental health program (CMHP). PARTICIPANTS: Undergraduate
      and graduate students receiving treatment at the CMHP from Jan-Dec 2015. METHODS:
      De-identified data was obtained via electronic health records for all students
      receiving care through the CMHP. RESULTS: 1.2 FTE clinical providers treated 278
      undergraduate and graduate students during the year (65.1% < age 26, 53.6%
      female, 49.6% caucasian). There were 1822 CMHP outpatient visits, 318 other
      medical visits and 103 total emergency room (ER)/inpatient visits. Ten students
      were identified as high utilizers of ER/inpatient services, while charges to the
      CMHP totaled $470,157 and total charges to the Health System were $2,378,315.
      CONCLUSIONS: Students with complex psychiatric/medical co-morbidities received
      cost effective, convenient and integrative treatment. Over time, we hope to
      intervene earlier and decrease ER/inpatient visits.

PMID- 29601287
TI  - Sexual vs. Non-sexual trauma, sexual satisfaction and function, and mental health
      in female veterans.
AB  - Trauma in general, and sexual assault in particular, is associated with serious
      mental health and functional problems. The quality of sexual
      satisfaction/function may be particularly impacted by sexual assault, and such
      sexual problems may account for some of the broader mental health and functioning
      impairments in sexual assault survivors. Accordingly, we examined self-reports of
      sexual health and mental health in a sample of 255 female veterans in committed,
      monogamous relationships who provided data regarding sexual assault (n = 153) or
      nonsexual trauma (n = 102). Trauma type was not associated with differences in
      sexual function, but sexual trauma was associated with significantly lower sexual
      satisfaction, greater posttraumatic stress disorder (PTSD) and depressive
      symptoms, and higher suicidal ideation. Furthermore, the indirect effect of
      trauma type on all mental health outcomes was significant via sexual satisfaction
      but not via sexual function. Finally, trauma type moderated the association of
      sexual function with suicidality, such that the association was significantly
      positive in those with a history of sexual assault but nonsignificant in those
      with nonsexual trauma. These results suggest that (1) female veterans' experience
      of sexual assault is related to sexual satisfaction, which in turn is related to
      mental health outcomes, and (2) a history of sexual assault may increase the
      importance of sexual functioning with regard to suicidality.

PMID- 29601288
TI  - Emotional numbing symptoms partially mediate the association between exposure to
      potentially morally injurious experiences and sexual anxiety for male service
      members.
AB  - Service members (SMs) returning from deployment are at risk of a range of sexual
      problems, some of which are thought to be related to psychological issues that
      may arise during deployment or combat. The current study sought to examine
      whether exposure to potentially morally injurious events (PMIEs) was associated
      with sexual anxiety (SA) above and beyond combat exposure and whether any such
      association was mediated by post-traumatic stress disorder (PTSD) symptom
      clusters. These questions were tested using data from self-report surveys
      collected from 221 partnered male Army (Active Duty, National Guard, or Reserve)
      SMs at three separate time points. Findings showed that exposure to PMIEs was
      significantly related to greater SA, with transgressions by self and perceived
      betrayal demonstrating unique associations when controlling for all factors of
      PMIEs. Moreover, total exposure to PMIEs was associated with SA above and beyond
      general combat exposure. PTSD symptoms partially mediated the association between
      exposure to PMIEs and SA, with emotional numbing accounting for significant
      unique indirect effects after controlling for other PTSD symptom clusters. The
      findings suggest that exposure to PMIEs is associated with SA, even when
      accounting for either combat exposure or PTSD symptoms, emphasizing the
      importance of this issue in understanding post-deployment problems in sexual
      intimacy.

PMID- 29601289
TI  - Sexuality and trauma: Intersections between sexual orientation, sexual
      functioning, and sexual health and traumatic events.

PMID- 29601290
TI  - A comparison of risk factors for various forms of trauma in the lives of lesbian,
      gay, bisexual and heterosexual homeless youth.
AB  - Numerous homeless youth experience trauma prior to leaving home and while on the
      street. Bullying and trading sex (i.e. exchanging sexual favors for survival
      items such as food) are additional forms of trauma experienced by many homeless
      youth. Although lesbian, gay, and bisexual (LGB) homeless youth experience higher
      rates of child abuse compared to their heterosexual counterparts, there is a
      paucity of research comparing these two groups. As such, we compare whether
      difficulties finding items of necessity (e.g. food) and different forms of trauma
      including child sexual abuse, being bullied, trading sex, and street sexual
      victimization significantly differ for LGB and heterosexual homeless youth.
      Bivariate results reveal that LGB youth have more trouble finding shelter and are
      more likely to trade sex compared to heterosexual youth. Logistic regression
      results show that trading sex is correlated with street sexual victimization. In
      the second model, we find that being female, experiencing more child sexual
      abuse, and ever having traded sex are all positively linked with street sexual
      victimization. LGB youth are over-represented among homeless youth populations
      and are also more likely to trade sex; therefore, these young people need
      services that are widely accessible and specific to their needs.

PMID- 29601291
TI  - On hate crime victimization: Rates, types, and links with suicide risk among
      sexual orientation minority special interest group members.
AB  - Hate crimes remain pressing traumatic events for sexual orientation minority
      adults. Previous literature documents patterns in which hate crime victimization
      is associated with elevated risk for poor mental health. The present paper held 2
      aims to advance literature. First, we investigated the rates and types of hate
      crime victimization among sexual orientation minority adults. Second, adopting a
      mental health amplification risk model, we evaluated whether symptoms of
      depression, impulsivity, or post-traumatic stress exacerbated the hate crime
      victimization-suicide risk link. Participants were 521 adult sexual orientation
      minority-identifying members of the National Coalition for Sexual Freedom (i.e.,
      a bondage and discipline, and sadomasochism-identifying sexuality special
      interest group). Participants completed demographic and mental health inventories
      via online administration. Results showed: (1) low rates of total lifetime hate
      crime victimization and (2) higher rates of interpersonal violence compared to
      property crime victimization within the sample. Regression results showed: (1)
      independent positive main effects of all 3 mental health symptom categories with
      suicide risk; (2) an interaction pattern in which impulsivity was positively
      associated with suicide risk for non-victims; and (3) an interaction pattern in
      which post-traumatic stress was positively associated with suicide risk for hate
      crime victims and non-victims. Results are discussed concerning implications for
      trauma-informed mental healthcare, mental health amplification models, and hate
      crime and suicide prevention policies.

PMID- 29601292
TI  - Treatment experiences among LGBT veterans with discrimination-based trauma
      exposure: A pilot study.
AB  - Past research suggests that rates of trauma exposure and Posttraumatic Stress
      Disorder (PTSD) are elevated among lesbian, gay, bisexual, and transgender (LGBT)
      veterans compared to heterosexual and cisgender veterans. Given higher rates of
      trauma exposure and PTSD, and the culture associated with the Department of
      Defense's history of policies excluding LGBT people, it is important to
      understand if LGBT veterans are seeking PTSD treatment following discrimination
      based traumatic events, where they seek care, and if they are satisfied with
      treatment. This study aimed to describe the experiences of discrimination-based
      trauma-exposed LGBT veterans' (n = 47) experiences with PTSD treatment, including
      location of treatment (Veterans Health Administration [VHA] versus non-VHA) and
      satisfaction with care. The majority of veterans had received a PTSD diagnosis
      from a health-care provider in their lifetimes (78.72%, n = 37), and over half
      reported currently experiencing PTSD symptoms. Approximately 47% of LGBT veterans
      with discrimination-based trauma histories preferred to seek PTSD treatment
      exclusively at VHA (46.81%) or with a combination of VHA and non-VHA services
      (38.30%). Veterans who received PTSD treatment exclusively from VHA reported
      higher satisfaction ratings (7.44 on 0-9 scale) than veterans who received PTSD
      treatment exclusively from outside VHA (5.25 on 0-9 scale). For veterans who
      sought PTSD treatment at both VHA and non-VHA facilities, there were no
      significant differences regarding satisfaction ratings for their PTSD treatment
      in the two settings. Results are discussed in terms of VHA's continued efforts to
      establish equitable, patient-centered health care for all veterans and the
      importance of non-VHA facilities to recognize veteran identities.

PMID- 29601293
TI  - A resilience framework: Sexual health trajectories of youth with maltreatment
      histories.
AB  - There is a wealth of knowledge regarding negative sexual outcomes experienced by
      youth with childhood maltreatment (CM) histories, yet a dearth of research
      examines healthy sexual development among these youth. This gap exists despite
      evidence of resilience highlighting alternative and healthy physical, social, and
      psychological futures for youth who were abused. This study tested whether
      trajectories of resilience identified in studies of psychological functioning
      were applicable to sexual health. Using data from the first four waves of the
      National Longitudinal Study of Adolescent to Adult Health, latent class growth
      analysis was conducted among individuals with histories of CM (N = 1,437). On
      average, participants were 15, 16, 21, and 28 years old, respectively, by waves
      of data collection. About half of the sample was female (55%), the majority were
      White (66%), and a sizeable portion had experienced multiple forms of CM prior to
      Wave I (38%). Controlling for CM severity, three distinct sexual health
      trajectory classes were identified: resilient, survival, and improving, which
      were differentiated by age and biological sex. Older participants' sexual health
      was more likely to diminish over time, girls were more likely to show gains in
      sexual health over time, and significant differences in levels of sexual
      behaviors between the classes were only present during adolescence. Findings
      support the need for increased attention on the potential for sexual health
      despite experiences of CM, and highlight the applicability of resilience theory
      to youth sexuality.

PMID- 29601294
TI  - Manfred Schmitt (1947-2018).

PMID- 29601295
TI  - Diagnosis is now indexed in PubMed.

PMID- 29601296
TI  - Identification of facilitators and barriers to residents' use of a clinical
      reasoning tool.
AB  - BACKGROUND: While there is some experimental evidence to support the use of
      cognitive forcing strategies to reduce diagnostic error in residents, the
      potential usability of such strategies in the clinical setting has not been
      explored. We sought to test the effect of a clinical reasoning tool on diagnostic
      accuracy and to obtain feedback on its usability and acceptability. METHODS: We
      conducted a randomized behavioral experiment testing the effect of this tool on
      diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a
      single internal medical residency program in 2014. Residents completed written
      clinical cases in a proctored setting with and without prompts to use the tool.
      The tool encouraged reflection on concordant and discordant aspects of each case.
      We used random effects regression to assess the effect of the tool on diagnostic
      accuracy of the independent case sets, controlling for case complexity. We then
      conducted audiotaped structured focus group debriefing sessions and reviewed the
      tapes for facilitators and barriers to use of the tool. RESULTS: Of 51 eligible
      PGY-3 residents, 34 (67%) participated in the study. The average diagnostic
      accuracy increased from 52% to 60% with the tool, a difference that just met the
      test for statistical significance in adjusted analyses (p=0.05). Residents
      reported that the tool was generally acceptable and understandable but did not
      recognize its utility for use with simple cases, suggesting the presence of
      overconfidence bias. CONCLUSIONS: A clinical reasoning tool improved residents'
      diagnostic accuracy on written cases. Overconfidence bias is a potential barrier
      to its use in the clinical setting.

PMID- 29601297
TI  - Laboratory error reporting rates can change significantly with year-over-year
      examination.
AB  - BACKGROUND: Incident reporting systems are useful tools to raise awareness of
      patient safety issues associated with healthcare error, including errors
      associated with the medical laboratory. METHODS: Previously, we presented the
      analysis of data compiled by the British Columbia Patient Safety & Learning
      System over a 3-year period. A second comparable set was collected and analyzed
      to determine if reported error rates would tend to remain stable or change.
      RESULTS: Compared to the original set, the second set presented changes that were
      both materially and statistically significant. Overall, the total number of
      reports increased by 297% with substantial changes between the pre-examination,
      examination and post-examination phases (chi2: 993.925, DF=20; p<0.00001). While
      the rate of change for pre-examination (clerical and collection) errors were not
      significantly different than the total year results, the rate of change for
      reporting examination errors rose by 998%. While the exact reason for dramatic
      change is not clear, possible explanations are provided. CONCLUSIONS:
      Longitudinal error rate tracking is a useful approach to monitor for laboratory
      quality improvement.

PMID- 29601298
TI  - Sepsis as a model for improving diagnosis.
AB  - Diagnostic safety could theoretically be improved by high-level interventions,
      such as improving clinical reasoning or eliminating system-related defects in
      care, or by focusing more specifically on a single problem or disease. In this
      review, we consider how the timely diagnosis of sepsis has evolved and improved
      as an example of the disease-focused approach. This progress has involved
      clarifying and revising the definitions of sepsis, efforts to raise awareness,
      faster and more reliable laboratory tests and a host of practice-level
      improvements based on health services research findings and recommendations. We
      conclude that this multi-faceted approach incorporating elements of the 'learning
      health system' model has improved the early recognition and treatment of sepsis,
      and propose that this model could be productively applied to improve timely
      diagnosis in other time-sensitive conditions.

PMID- 29601299
TI  - Becoming a teacher of clinical reasoning.
AB  - Diagnostic reasoning is one of the most challenging and rewarding aspects of
      clinical practice. As a result, facility in teaching diagnostic reasoning is a
      core necessity for all medical educators. Clinician educators' limited
      understanding of the diagnostic process and how expertise is developed may result
      in lost opportunities in nurturing the diagnostic abilities of themselves and
      their learners. In this perspective, the authors describe their journeys as
      clinician educators searching for a coherent means of teaching diagnostic
      reasoning. They discuss the initial appeal and immediate applicability of dual
      process theory and cognitive biases to their own clinical experiences and those
      of their trainees, followed by the eventual and somewhat belated recognition of
      the importance of context specificity. They conclude that there are no quick
      fixes in guiding learners to expertise of diagnostic reasoning, but rather the
      development of these abilities is best viewed as a long, somewhat frustrating,
      but always interesting journey. The role of the teacher of clinical reasoning is
      to guide the learners on this journey, recognizing true mastery may not be
      attained, but should remain a goal for teacher and learner alike.

PMID- 29601300
TI  - Cannabinoids in health and disease: pharmacological potential in metabolic
      syndrome and neuroinflammation.
AB  - The use of different natural and/or synthetic preparations of Cannabis sativa is
      associated with therapeutic strategies for many diseases. Indeed, thanks to the
      widespread diffusion of the cannabinoidergic system in the brain and in the
      peripheral districts, its stimulation, or inhibition, regulates many
      pathophysiological phenomena. In particular, central activation of the
      cannabinoidergic system modulates the limbic and mesolimbic response which leads
      to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory
      response. In this review a brief history of cannabinoids and the protagonists of
      the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main
      receptors, will be described. Furthermore, the pharmacological effects of
      cannabinoids will be outlined. An overview of the involvement of the
      endocannabinoidergic system in neuroinflammatory and metabolic pathologies will
      be made. Finally, particular attention will also be given to the new
      pharmacological entities acting on the two main receptors, cannabinoid receptor
      type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the
      neuroinflammatory and metabolic mechanisms involved.

PMID- 29601301
TI  - On "A mutual information estimator with exponentially decaying bias" by Zhang and
      Zheng.
AB  - Zhang, Z. and Zheng, L. (2015): "A mutual information estimator with
      exponentially decaying bias," Stat. Appl. Genet. Mol. Biol., 14, 243-252,
      proposed a nonparametric estimator of mutual information developed in entropic
      perspective, and demonstrated that it has much smaller bias than the plugin
      estimator yet with the same asymptotic normality under certain conditions.
      However it is incorrectly suggested in their article that the asymptotic
      normality could be used for testing independence between two random elements on a
      joint alphabet. When two random elements are independent, the asymptotic
      distribution of $?sqrt{n}$n-normed estimator degenerates and therefore the
      claimed normality does not hold. This article complements Zhang and Zheng by
      establishing a new chi-square test using the same entropic statistics for mutual
      information being zero. The three examples in Zhang and Zheng are re-worked using
      the new test. The results turn out to be much more sensible and further
      illustrate the advantage of the entropic perspective in statistical inference on
      alphabets. More specifically in Example 2, when a positive mutual information is
      known to exist, the new test detects it but the log likelihood ratio test fails
      to do so.

PMID- 29601302
TI  - Drug error in paediatric anaesthesia: current status and where to go now.
AB  - PURPOSE OF REVIEW: Medication errors in paediatric anaesthesia and the
      perioperative setting continue to occur despite widespread recognition of the
      problem and published advice for reduction of this predicament at international,
      national, local and individual levels. Current literature was reviewed to
      ascertain drug error rates and to appraise causes and proposed solutions to
      reduce these errors. RECENT FINDINGS: The medication error incidence remains
      high. There is documentation of reduction through identification of causes with
      consequent education and application of safety analytics and quality improvement
      programs in anaesthesia departments. Children remain at higher risk than adults
      because of additional complexities such as drug dose calculations, increased
      susceptibility to some adverse effects and changes associated with growth and
      maturation. Major improvements are best made through institutional system changes
      rather than a commitment to do better on the part of each practitioner. SUMMARY:
      Medication errors in paediatric anaesthesia represent an important risk to
      children and most are avoidable. There is now an understanding of the genesis of
      adverse drug events and this understanding should facilitate the implementation
      of known effective countermeasures. An institution-wide commitment and strategy
      are the basis for a worthwhile and sustained improvement in medication safety.

PMID- 29601303
TI  - The opioid epidemic and pregnancy: implications for anesthetic care.
AB  - PURPOSE OF REVIEW: This review summarizes evolving knowledge regarding adverse
      maternal, fetal, and neonatal effects of opioid exposure during pregnancy, and
      current treatment options for opioid use disorder (OUD). Maternal and fetal
      implications of maternal opioid maintenance with methadone and buprenorphine are
      described. Finally, acute and chronic pain management strategies in opioid
      tolerant parturients are reviewed. RECENT FINDINGS: Opioid use among parturients
      has risen dramatically, with opioid use during pregnancy as high as 20%. Of women
      with chronic pain, most continue to take opioids during pregnancy. Medication
      assisted therapy with methadone or buprenorphine is currently the standard for
      treatment of opiate use disorder. Buprenorphine has unique pharmacologic
      properties that account for its preference over methadone. It has also been shown
      to produce more favorable neonatal outcomes compared with methadone. Increased
      clearance and volume of distribution associated with pregnancy require adjustment
      of dosing regimens of both medications. Multimodal adjuncts can be important
      alternatives for treatment of pain in opioid-tolerant parturients. SUMMARY: The
      dramatic rise in OUD in pregnancy has had staggering socioeconomic consequences,
      carrying with it profound maternal and fetal health problems. Medication-assisted
      treatment utilizing either methadone, or more commonly buprenorphine, is
      considered the standard of care for OUD during pregnancy. Peripartum pain
      management for opioid-tolerant patients is challenging and requires consideration
      for regional anesthesia along with multimodal pharmacotherapy.

PMID- 29601304
TI  - Episodic syndromes of childhood associated with migraine.
AB  - PURPOSE OF REVIEW: This review covers recent advances in our understanding of
      episodic syndromes that may be associated with migraine in children and
      adolescents, as well as what is known about the treatment of these disorders.
      RECENT FINDINGS: The episodic syndromes include benign paroxysmal torticollis,
      benign paroxysmal vertigo, abdominal migraine, and cyclic vomiting syndrome.
      Infant colic, or excessive crying in an otherwise healthy and well fed infant,
      may also fit into this category and is included in the appendix section of the
      most recent edition of the International Classification of Headache Disorders.
      SUMMARY: Episodic syndromes are considered to be early life expressions of
      migraine in the developing brain. Additional research is needed to determine,
      which acute and preventive treatments are the most effective in managing these
      disorders.

PMID- 29601305
TI  - Noninvasive neuromodulation in migraine and cluster headache.
AB  - PURPOSE OF REVIEW: The purpose of this narrative review is to provide an overview
      of the currently available noninvasive neuromodulation devices for the treatment
      of migraine and cluster headache. RECENT FINDINGS: Over the last decade, several
      noninvasive devices have undergone development and clinical trials to evaluate
      efficacy and safety. Based on this body of work, single-pulse transcranial
      magnetic stimulation, transcutaneous supraorbital neurostimulation, and
      noninvasive vagal nerve stimulation devices have been cleared by the United
      States Food and Drug Administration and are available for clinical use for the
      treatment of primary headache disorders. SUMMARY: Overall, these novel
      noninvasive devices appear to be safe, well tolerated, and have demonstrated
      promising results in clinical trials in both migraine and cluster headache. This
      narrative review will provide a summary and update of the proposed mechanisms of
      action, evidence, safety, and future directions of various currently available
      modalities of noninvasive neuromodulation for the treatment of migraine and
      cluster headache.

PMID- 29601306
TI  - Evidence-based guidelines in lower urinary tract symptoms secondary to benign
      prostatic hyperplasia and variation in care.
AB  - PURPOSE OF REVIEW: Guidelines have been developed to assist physicians in the
      diagnosis and management of patients with lower urinary tract symptoms. These
      guidelines vary in the level of evidence used and the strength of their
      recommendations. With variations in guidelines, multiple variations in clinical
      practice may also been seen. RECENT FINDINGS: Although examinations of physician
      compliance with benign prostatic hyperplasia (BPH) guidelines date back to the
      1980s, researchers have become more interested in closer examination of guideline
      compliance. Furthermore, guidelines themselves are becoming more robust
      documents, with the American Urological Association and European Association of
      Urology guidelines updated in 2014 and 2015, respectively. This review examines
      both the evidence base behind these BPH guidelines and the variations in clinical
      care related to the guidelines. SUMMARY: Despite over 40 years of study,
      variations continue to occur in the work up and treatment of men with BPH. With
      the proliferation of medications and surgical procedures available for
      symptomatic lower urinary tract symptoms (LUTS) due to BPH, we will continue to
      see this variation in care. Our current guidelines can help mitigate this
      variation by providing a baseline set of assessments and algorithms for routine
      patients. However, only through continued refinement will the guidelines meet
      their full potential. The prior review shows how the evidence base is limited for
      the diagnostic work up for LUTS, provides limited information on comparative
      effectiveness of therapies in LUTS and BPH, and has not led to consistency
      between guidelines.

PMID- 29601307
TI  - Applying American Society of Addiction Medicine Performance Measures in
      Commercial Health Insurance and Services Data.
AB  - OBJECTIVES: ASAM's Standards of Care for the Addiction Specialist established
      appropriate care for the treatment of substance use disorders. ASAM identified
      three high priority performance measures for specification and testing for
      feasibility in various systems using administrative claims: use of
      pharmacotherapy for alcohol use disorder (AUD); use of pharmacotherapy for opioid
      use disorder (OUD); and continuity of care after withdrawal management services.
      This study adds to the initial testing of these measures in the Veteran's Health
      Administration (VHA) by testing the feasibility of specifications in commercial
      insurance data (Cigna). METHODS: Using 2014 and 2015 administrative data, the
      proportion of individuals with an AUD or OUD diagnosis each year who filled
      prescriptions or were dispensed appropriate FDA-approved pharmacotherapy. For
      withdrawal management follow up, the proportion with an outpatient encounter
      within seven days was calculated. The sensitivity of specifications was also
      tested. RESULTS: Rates of pharmacotherapy for AUD ranged from 6.2% to 7.6%
      (depending on year and specification details), and rates for OUD pharmacotherapy
      were 25.0% to 29.7%. Seven-day follow up rate after withdrawal management in an
      outpatient setting was 20.5%, and an additional 39.7% in an inpatient or
      residential setting. CONCLUSIONS: Application of ASAM specifications is feasible
      in commercial administrative data. Because of varying system needs and payment
      practices across health systems, measures may require adjustment for different
      settings. Moving forward, important focus will be on the continued refinement of
      these measures with the new ICD-10 coding systems, new formulations of current
      medications, and new payment approaches such as bundled payment.

PMID- 29601308
TI  - Real-world application of currently available decision models for dual
      antiplatelet therapy duration in acute coronary syndrome.

PMID- 29601309
TI  - Anatomical and procedural predictors of pulmonary vein stenosis in the setting of
      second-generation cryoballoon ablation.
AB  - AIMS: Pulmonary vein stenosis (PVS) is a well recognized complication as a
      consequence of pulmonary vein isolation. In the current study, we sought to
      analyze potential anatomical and intraprocedural predictors of PVS during second
      generation cryoballoon ablation, particularly focusing on the impact of freeze
      duration and number of cryoapplications. METHODS: Fifty-four patients who
      underwent cryoballoon ablation for atrial fibrillation were included
      retrospectively in this study. All patients underwent cardiac-enhanced
      multidetector computed tomography both before and after the ablation. The
      exclusion criteria were any contraindications for the procedure, including the
      presence of an intracavitary thrombus, uncontrolled heart failure and
      contraindications to general anesthesia. RESULTS: Mild (25-50%) PVS was only
      detected in one vein (0.4%) and neither moderate (50-75%) nor severe (>75%) PVS
      were found. Twenty-five pulmonary veins (12%) exhibited slight narrowing of the
      diameter (less than 25%). In the univariate analysis, a longer duration of
      cryoapplication and a larger pulmonary vein ostium preprocedure diameter and area
      were independently associated with pulmonary vein narrowing [odds ratio (OR):
      1.004; confidence interval (CI): 1.001-1.008, P = 0.016; OR: 1.250, CI: 1.090
      1.434, P = 0.001 and OR: 1.006; CI: 1.002-1.011, P = 0.006] respectively.
      CONCLUSION: Longer duration of cryoablation, an increased number of applications
      per vein and larger pulmonary vein ostia are associated with a higher risk of
      pulmonary vein diameter and area reduction. These findings might suggest to lower
      the dosing to a single and shorter application if isolation is attained, to
      reduce the possibility of future pulmonary vein narrowing.

PMID- 29601310
TI  - Ticagrelor-related late-onset dyspnea as cause of emergency department visit: a 3
      year outpatient study.
AB  - INTRODUCTION: The aim of the current study was to define the rate of emergency
      department visits for late-onset dyspnea in acute coronary syndrome patients
      treated with ticagrelor. METHODS: We conducted a population-based study on about
      850 000 residents of Florence metropolitan area, by using data from healthcare
      records. RESULTS: Between 2012 and 2014, 1073 subjects in Florence metropolitan
      area had at least one prescription of ticagrelor. Two-hundred and thirty-four
      patients were diagnosed with 'respiratory system or other chest symptoms' or
      'other diseases of lung', and among them we identified 20 subjects with
      ticagrelor-related late-onset dyspnea. These, and the 979 nonevent subjects
      (receiving ticagrelor but not developing dyspnea), contributed to 413 person
      years overall. The dyspnea rate was 4.84 per 100 person-years (95% confidence
      interval: 3.12-7.51). CONCLUSION: Late-onset dyspnea rate is notably lower than
      early-onset one; nevertheless prescribing clinicians should be aware that about
      one in 20 outpatients with a stabilized ticagrelor treatment might develop a
      dyspnea leading to an emergency department visit, and they should consider
      ticagrelor replacement only in patients who cannot tolerate dyspnea.

PMID- 29601312
TI  - Myeloid cells regulate plasma LDL-cholesterol levels.
AB  - PURPOSE OF REVIEW: Leukocytosis, elevated blood leukocyte levels, is associated
      with enhanced cardiovascular risk in humans. Hematopoietic stem and progenitor
      cells (HSPCs) drive leukocyte production in a process called hematopoiesis, which
      mainly occurs in the bone marrow, and under certain conditions also in other
      organs such as the spleen. Cholesterol accumulation in HSPCs enhances
      hematopoiesis, increasing levels of blood monocytes that infiltrate into
      atherosclerotic plaques. Although HSPC proliferation and monocytosis enhance
      atherogenesis in several studies, concomitant decreases in LDL-cholesterol levels
      have also been reported, associated with anti-atherogenic effects. This review
      focuses on the link between HSPC proliferation, leukocytosis, plasma LDL
      cholesterol levels, and atherogenesis. RECENT FINDINGS: Recent studies have shown
      that an acute infection enhances cholesterol accumulation in HSPCs, driving HSPC
      proliferation, and leading to the expansion of myeloid cells (monocytes,
      neutrophils, and macrophages). Enhanced hematopoiesis is associated with low
      plasma LDL-cholesterol levels in animal models and humans, probably because of
      the increased number of myeloid cells that take up LDL-cholesterol. Despite low
      plasma LDL-cholesterol levels, specific patient populations with enhanced
      hematopoiesis show increased cardiovascular risk. SUMMARY: Enhanced hematopoiesis
      and monocytosis may accelerate atherogenesis. Studies on these processes may lead
      to the identification of new therapeutic targets for cardiovascular diseases.

PMID- 29601311
TI  - Classical and alternative roles for autophagy in lipid metabolism.
AB  - PURPOSE OF REVIEW: Intracellular lipid metabolism is a complex interplay of
      exogenous lipid handling, trafficking, storage, lipolysis, and export. Recent
      work has implicated the cellular degradative process called autophagy in several
      aspects of lipid metabolism. We will discuss both the classical and novel roles
      of autophagy and the autophagic machinery in this setting. RECENT FINDINGS: The
      delivery of lipid droplets to lysosomes for hydrolysis, named lipophagy, was the
      first described functional role for autophagy in lipid metabolism. The molecular
      machinery and regulation of this selective form of macroautophagy is beginning to
      be discovered and has the potential to shed enormous light on intracellular
      lipolysis. Yet, the autophagic machinery appears to also be coopted for
      alternative roles that include interaction with cytosolic lipolysis pathways,
      supply and expansion of lipid droplets, and lipoprotein trafficking.
      Additionally, lesser studied forms of autophagy called microautophagy and
      chaperone-mediated autophagy have distinct roles in lipid handling that also
      intersect with classical macroautophagy. The integration of current knowledge in
      these areas into a holistic understanding of intracellular lipid metabolism will
      be a goal of this review. SUMMARY: As the field of autophagy has evolved and
      expanded to include functional roles in various aspects of cellular degradation,
      so has its role in intracellular lipid metabolism. Understanding the mechanisms
      underlying these classical and alternative roles of autophagy will not only
      enhance our knowledge in lipid biology but also provide new avenues of
      translation to human lipid disorders.

PMID- 29601313
TI  - Increasing the Number of Medical Emergency Calls Does Not Improve Hospital
      Mortality.
AB  - OBJECTIVES: Medical emergency teams were established to rescue patients
      experiencing clinical deterioration thus preventing cardiac arrest and unexpected
      hospital mortality. Although hospitals are encouraged to increase emergency
      calling rates to improve in-hospital mortality, there are increasing concerns
      about the impact these calls have on the workload of the teams and the skill
      levels on the general wards. We set out to examine the relationship between
      emergency calling rates and adjusted in-hospital mortality. DESIGN: Retrospective
      analysis of prospectively collected patient and emergency call data. SETTING:
      Tertiary, metropolitan, and regional hospitals in the State of Victoria,
      Australia. PATIENTS: Consecutive patients discharged from 1) St Vincent's
      Hospital Melbourne from January 2008 to June 2016 and 2) 15 Victorian hospitals
      from July 2010 to June 2015. MEASUREMENTS AND MAIN RESULTS: We studied 441,029
      patients from St Vincent's Hospital Melbourne. Median age was 61.0 years
      (interquartile range, 45-74 yr), 57.2% were men, and 0.70% died; monthly
      emergency calling rates varied between 9.21 and 30.69 (median 18.4) per 1,000
      discharges. In-hospital mortality adjusted for age, gender, emergency status,
      same day admission, year of discharge, and Charlson Comorbidity Index was not
      reduced by higher calling rates in the month of discharge (odds ratio, 1.019; 95%
      CI, 1.008-1.031). We then examined 3,339,789 discharges from 15 Victorian
      hospitals with median age 61 years (interquartile range, 43-74 yr), 51.4% men,
      and hospital mortality 0.83% where yearly emergency calling rates varied from
      18.46 to 33.40 (median, 25.75) per 1,000 discharges. Again, adjusted mortality
      was not reduced by higher calling rates in the year of discharge (odds ratio,
      1.003; 95% CI, 1.001-1.006). CONCLUSIONS: With adjustment for patient factors,
      illness, and comorbidities, increased emergency calling rates were not associated
      with reduced in-hospital mortality. Efforts to increase calling rates do not seem
      warranted.

PMID- 29601314
TI  - Diagnostic Accuracy of Chest Radiograph, and When Concomitantly Studied Lung
      Ultrasound, in Critically Ill Patients With Respiratory Symptoms: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVES: Chest radiograph is considered the first-line diagnostic imaging
      modality for patients presenting with pulmonary symptoms in the ICU. In this meta
      analysis, we aim to evaluate the diagnostic accuracy of chest radiograph, and
      when concomitantly studied lung ultrasound, in comparison with the gold-standard
      CT for adult critically ill patients with respiratory symptoms. DATA SOURCES:
      PubMed, EMBASE, and Gray literature. STUDY SELECTION: Studies comparing chest
      radiograph, and if performed lung ultrasound, with CT for adult ICU patients with
      respiratory symptoms. DATA EXTRACTION: Quality was scored with Quality Assessment
      of Diagnostic Accuracy Studies-2, and study setting, test characteristics, and
      study design were extracted. DATA SYNTHESIS: In the meta-analysis, we included 10
      full-text studies, including 543 patients, and found that chest radiograph has an
      overall sensitivity of 49% (95% CI, 40-58%) and specificity of 92% (86-95%). In
      seven studies, where also lung ultrasound was studied, lung ultrasound had an
      overall sensitivity of 95% (92-96%) and specificity of 94% (90-97%). Substantial
      heterogeneity was found. A planned subgroup analysis for individual pathologies
      was performed. The results of four abstract-only studies, included in the
      systematic review, were considered unlikely to significantly influence results of
      our meta-analysis. Study limitations were that most studies were of low power
      combined with methodological limitations. CONCLUSIONS: This meta-analysis
      demonstrates that chest radiograph has a low sensitivity and reasonable
      specificity compared with CT for detecting lung pathology in critically ill
      patients. The studies also investigating lung ultrasound, showed lung ultrasound
      to be clearly superior to chest radiograph in terms of sensitivity with similar
      specificity, thereby opting to be the first-line diagnostic tool in these
      patients.

PMID- 29601315
TI  - Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients
      Following Traumatic Brain Injury.
AB  - OBJECTIVES: Therapeutic hypothermia has been of topical interest for many years
      and with the publication of two international, multicenter randomized controlled
      trials, the evidence base now needs updating. The aim of this systematic review
      of randomized controlled trials is to assess the efficacy of therapeutic
      hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes,
      and new pneumonia. DATA SOURCES: The following databases were searched from
      January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled
      Trial, MEDLINE, PubMed, and EMBASE. STUDY SELECTION: Only foreign articles
      published in the English language were included. Only articles that were
      randomized controlled trials investigating adult traumatic brain injury sustained
      following an acute, closed head injury were included. Two authors independently
      assessed at each stage. DATA EXTRACTION: Quality was assessed using the Cochrane
      Collaboration's tool for assessing the risk of bias. All extracted data were
      combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs.
      p value of less than 0.05 was considered statistically significant. All
      statistical analyses were conducted using RevMan 5 (Cochrane Collaboration,
      Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration,
      2014). DATA SYNTHESIS: Twenty-two studies with 2,346 patients are included.
      Randomized controlled trials with a low risk of bias show significantly more
      mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04
      1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias
      show the opposite with a higher mortality in the control group (risk ratio, 0.70;
      95% CI, 0.60-0.82; p < 0.00001). CONCLUSIONS: Overall, this review is in-keeping
      with the conclusions published by the most recent randomized controlled trials.
      High-quality studies show no significant difference in mortality, poor outcomes,
      or new pneumonia. In addition, this review shows a place for fever control in the
      management of traumatic brain injury.

PMID- 29601317
TI  - Fatal Case of Acute Cardiac Failure After Long-Term Physical Restraint of Patient
      Treated With Clozapine in Psychiatric Ward.

PMID- 29601316
TI  - Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive
      Disorder Halted Due to Intolerability.
AB  - BACKGROUND: Some glutamatergic modulators have demonstrated rapid and relatively
      sustained antidepressant properties in patients with major depressive disorder.
      Because the potassium channel activator diazoxide increases glutamate uptake via
      potassium channel activation, we hypothesized that it might exert antidepressant
      effects by increasing the removal of glutamate from the synaptic cleft, thereby
      reducing excessive glutamate transmission. METHODS: This randomized, double
      blind, placebo-controlled, crossover, single-site inpatient clinical study was
      conducted at the National Institute of Mental Health to assess the efficacy and
      safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3
      week course of placebo in 6 participants with treatment-refractory major
      depressive disorder. The primary clinical outcome measure was change in
      Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment.
      Quantitative insulin sensitivity check index, as well as concomitant imaging
      measures (electroencephalography, proton magnetic resonance spectroscopy,
      magnetoencephalography), were used as potential surrogate markers of target (KATP
      channel) engagement. RESULTS: The study was halted due to severe adverse effects.
      Given the small sample size, statistical evaluation of the effect of diazoxide on
      Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not
      pursued. Visual inspection of the quantitative insulin sensitivity check index
      test revealed no evidence of target engagement. CONCLUSIONS: Although the results
      are negative, they are an important addition to the literature in this rapidly
      changing field.

PMID- 29601318
TI  - Resolution of Acute-Onset Depersonalization/Derealization With Clonazepam and
      Inpatient Hospitalization.

PMID- 29601319
TI  - Long-Term Near-Infrared Photobiomodulation for Anxious Depression Complicated by
      Takotsubo Cardiomyopathy.

PMID- 29601320
TI  - Esophageal pressure monitoring: why, when and how?
AB  - PURPOSE OF REVIEW: Esophageal manometry has shown its usefulness to estimate
      transpulmonary pressure, that is lung stress, and the intensity of spontaneous
      effort in patients with acute respiratory distress syndrome. However, clinical
      uptake of esophageal manometry in ICU is still low. Thus, the purpose of review
      is to describe technical tips to adequately measure esophageal pressure at the
      bedside, and then update the most important clinical applications of esophageal
      manometry in ICU. RECENT FINDINGS: Each esophageal balloon has its own
      nonstressed volume and it should be calibrated properly to measure pleural
      pressure accurately: transpulmonary pressure calculated on absolute esophageal
      pressure reflects values in the lung regions adjacent to the esophageal balloon
      (i.e. dependent to middle lung). Inspiratory transpulmonary pressure calculated
      from airway plateau pressure and the chest wall to respiratory system elastance
      ratio reasonably reflects lung stress in the nondependent 'baby' lung, at highest
      risk of hyperinflation. Also esophageal pressure can be used to detect and
      minimize patient self-inflicted lung injury. SUMMARY: Esophageal manometry is not
      a complicated technique. There is a large potential to improve clinical outcome
      in patients with acute respiratory distress syndrome, acting as an early detector
      of risk of lung injury from mechanical ventilation and vigorous spontaneous
      effort.

PMID- 29601321
TI  - Predicting adverse hemodynamic events in critically ill patients.
AB  - PURPOSE OF REVIEW: The art of predicting future hemodynamic instability in the
      critically ill has rapidly become a science with the advent of advanced
      analytical processed based on computer-driven machine learning techniques. How
      these methods have progressed beyond severity scoring systems to interface with
      decision-support is summarized. RECENT FINDINGS: Data mining of large
      multidimensional clinical time-series databases using a variety of machine
      learning tools has led to our ability to identify alert artifact and filter it
      from bedside alarms, display real-time risk stratification at the bedside to aid
      in clinical decision-making and predict the subsequent development of
      cardiorespiratory insufficiency hours before these events occur. This fast
      evolving filed is primarily limited by linkage of high-quality granular to
      physiologic rationale across heterogeneous clinical care domains. SUMMARY: Using
      advanced analytic tools to glean knowledge from clinical data streams is rapidly
      becoming a reality whose clinical impact potential is great.

PMID- 29601323
TI  - Early-phase Innate Immune Suppression in Murine Severe Sepsis Is Restored with
      Systemic Interferon-beta.
AB  - BACKGROUND: Sepsis is a leading cause of death in the intensive care unit. Immune
      modulatory therapy targeting sepsis-associated proinflammatory responses has not
      shown survival benefit. Here, the authors evaluated innate immunity at the early
      stage of murine mild or severe peritoneal sepsis induced by cecal ligation and
      puncture, and the effect of systemic interferon-beta, a potent inflammatory
      mediator, on severe sepsis as well as its mechanism of action. METHODS: Mild and
      severe sepsis was induced in C57BL/6 mice by cecal ligation and puncture with 22-
      and 18-gauge needles for puncture, respectively. Interferon-beta (700 U/g) was
      subcutaneously administered either before or 12 h after cecal ligation and
      puncture for the severe sepsis group. RESULTS: Severe sepsis resulted in
      significantly lower 6-day survival rates than mild sepsis (n = 48, 25% vs. n =
      11, 81.8%, P = 0.002), significantly less phagocytic capacity of peritoneal
      exudate cells, and lower CXC chemokine receptor-2 expression on circulating
      neutrophils at 24 h after cecal ligation and puncture. Interferon-beta
      administration 12 h after cecal ligation and puncture associated with
      significantly improved survival (n = 34, 52.9%, P = 0.017) increased the number
      and function of peritoneal exudate cells, peritoneal/systemic inflammatory
      cytokine/chemokine concentrations, and CXC chemokine receptor-2 on neutrophils,
      compared with the severe sepsis controls. However, those responses were not
      observed in the prophylactic interferon-beta group (n = 24). Interferon-beta
      increased lipopolysaccharide-induced interleukin-6 messenger RNA/protein
      expression of lipopolysaccharide-tolerant murine peritoneal macrophages, which
      was not observed in nontolerant cells. CONCLUSIONS: In severe sepsis, immune
      suppression occurs within 24 h and is associated with worse mortality. Interferon
      beta given after the onset of peritonitis restores impaired innate immunity in
      vivo and in vitro.

PMID- 29601322
TI  - Peripherally Acting MU-Opioid Receptor Agonists Attenuate Ongoing Pain-associated
      Behavior and Spontaneous Neuronal Activity after Nerve Injury in Rats.
AB  - BACKGROUND: Ongoing neuropathic pain is difficult to treat. The authors examined
      whether dermorphin [D-Arg2, Lys4] (1-4) amide, a peripherally acting u-opioid
      receptor agonist, attenuates ongoing pain-associated manifestations after nerve
      injury in rats and mice. METHODS: Using conditioned place preference assay, the
      authors tested whether animals show a preference to the environment associated
      with drug treatment. Wide-dynamic range and dorsal root ganglion neuronal
      activities were measured by electrophysiology recording and calcium imaging.
      RESULTS: Nerve-injured animals stayed longer in dermorphin [D-Arg2, Lys4] (1-4)
      amide-paired chamber after conditioning than during preconditioning (rats: 402.4
      +/- 61.3 vs. 322.1 +/- 45.0 s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 +/- 59.4
      vs. 351.3 +/- 95.9 s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application
      of dermorphin [D-Arg2, Lys4] (1-4) amide (5 MUM, 1 MUl, n = 5) reduced the
      numbers of small-diameter dorsal root ganglion neurons that showed spontaneous
      activity (1.1 +/- 0.4 vs. 1.5 +/- 0.3, P = 0.044) and that were activated by test
      stimulation (15.5 +/- 5.5 vs. 28.2 +/- 8.2, P = 0.009) after injury. In
      neuropathic rats, dermorphin [D-Arg2, Lys4] (1-4) amide (10 mg/kg, n = 8)
      decreased spontaneous firing rates in wide-dynamic range neurons to 53.2 +/-
      46.6% of predrug level, and methylnaltrexone (5 mg/kg, n = 9) blocked dermorphin
      [D-Arg2, Lys4] (1-4) amide-induced place preference and inhibition of wide
      dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1-4) amide increased paw
      withdrawal threshold (17.5 +/- 2.2 g) from baseline (3.5 +/- 0.7 g, 10 mg/kg, n =
      8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated
      administrations. CONCLUSIONS: Peripherally acting MU-opioids may attenuate
      ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated
      administrations cause antiallodynic tolerance.

PMID- 29601324
TI  - Neisseria gonorrhoeae vaccine development: hope on the horizon?
AB  - PURPOSE OF REVIEW: Neisseria gonorrhoeae is one of the most common causes of
      sexually transmitted infections, with an estimated more than 100 million cases of
      gonorrhea each year worldwide. N. gonorrhoeae has gained recent increasing
      attention because of the alarming rise in incidence and the widespread emergence
      of multidrug-resistant gonococcal strains. Vaccine development is one area of
      renewed interest. Herein, we review the recent advances in this area. RECENT
      FINDINGS: Vaccine development for N. gonorrhoeae has been problematic, but recent
      progress in the field has provided new hope that a gonococcal vaccine may be
      feasible. Several new vaccine antigens have been characterized in various models
      of infection. Furthermore, the first potential vaccine-induced protection against
      gonorrhea in humans has been reported, with decreased rates of gonorrhea
      described among individuals vaccinated with the Neisseria meningitidis serogroup
      B vaccine, MeNZB. SUMMARY: As antibiotic resistance continues to increase,
      vaccine development for N. gonorrhoeae becomes more urgent. The MeNZB vaccine is
      shown to have efficacy, albeit relatively low, against N. gonorrhoeae. This
      finding has the potential to reinvigorate research in the field of gonococcal
      vaccine development and will guide future studies of the antigens and
      mechanism(s) required for protection against gonococcal infection.

PMID- 29601325
TI  - Group A Streptococcus infections in children: from virulence to clinical
      management.
AB  - PURPOSE OF REVIEW: Recent findings have open new perspectives on group A
      Streptococcus (GAS) virulence understanding with special focus on the carrier
      stage and new hopes for an efficient vaccine against this important pathogen.
      RECENT FINDINGS: Understanding of carriage state, transmission and role of
      virulence factors in invasive infections have been recently active research
      fields questioning the link between carriage and infections and highlighting the
      potential to prevent invasive diseases. New roles for already well known
      virulence factors, such as Streptolysin O, M protein or NAD(+)-glycohydrolase
      have been discovered. Immunological studies have also shown diversity in both
      clinical and immunological responses toward various GAS antigens raising
      questions, and hopes, for the development of an efficient global vaccine
      candidate. SUMMARY: A greater understanding of GAS virulence strategies, and
      their associated clinical manifestations, may be obtained by shifting our
      research scope toward virulence determinant interactions and cooperation rather
      than focusing on individual virulence factor or specific strain characterization
      only.

PMID- 29601326
TI  - Human adenovirus infections: update and consideration of mechanisms of viral
      persistence.
AB  - PURPOSE OF REVIEW: To provide an update on recent studies of human adenoviral
      (HAdV) infections and to explore the mechanisms of viral persistence and the role
      of persistent infection in disseminated disease in immunocompromised patients.
      RECENT FINDINGS: Human adenoviruses continue to be a problem in ophthalmology
      clinics and to cause periodic, limited, global outbreaks of respiratory disease.
      Ad14p1 remains in worldwide circulation and continues to result in miniepidemics
      of severe respiratory infections. New variants of Ad4 and Ad7 have emerged in
      both the United States and Asia. The severity of Ad4 infections in outbreaks
      appears to depend more on preexisting conditions in patients than on genetically
      determined, viral virulence factors, in contrast to limited evidence of Ad7
      mutations that may convey increased viral pathogenesis. Reactivation of
      persistent adenovirus infection appears to be the primary source of disseminated
      infections in immunocompromised patients. New studies suggest that establishment
      of persistent infection and reactivation are related to variations in interferon
      mediated control of viral replication. SUMMARY: Innate immune responses can
      create a state of adenoviral persistence, and repression of these host defenses
      can result in reactivation and dissemination of infection. A better definition of
      the molecular mechanisms of immune-mediated control of viral replication might
      lead to new strategies for treatment of HAdV reactivation and dissemination.

PMID- 29601327
TI  - Peripartum cardiomyopathy: approach to management.
AB  - PURPOSE OF REVIEW: To provide recommendations for the diagnosis and management of
      patients with peripartum cardiomyopathy (PPCM). RECENT FINDINGS: PPCM is
      pregnancy-associated myocardial disease that occurs during pregnancy or
      postpartum and is characterized by the development of heart failure due to marked
      left ventricular (LV) systolic dysfunction. The disease is relatively uncommon,
      but its incidence is increasing, and it remains an important cause of cardiac
      related maternal morbidity and mortality in previously healthy young women. With
      early diagnosis and treatment, the majority of the patients demonstrate recovery.
      SUMMARY: The review provides information on the clinical presentation, prognosis
      and contemporary management of PPCM as well as the approach to subsequent
      pregnancies, labor and delivery and long-term psychological consequences of the
      disease.

PMID- 29601328
TI  - Statin loading in cardiovascular surgery: never too early to treat.
AB  - PURPOSE OF REVIEW: The effects of statin loading before, during or after vascular
      interventions on cardiovascular and renal outcomes are discussed. Furthermore,
      the selection of optimal statin type and dose, according to current evidence or
      guidelines, is considered. The importance of treating statin intolerance and
      avoiding statin discontinuation is also discussed. RECENT FINDINGS: Statin
      loading has been shown to beneficially affect cardiovascular outcomes, total
      mortality and/or contrast-induced acute kidney injury, in patients undergoing
      vascular procedures such as percutaneous coronary intervention (PCI), coronary
      artery bypass grafting (CABG), carotid endarterectomy (CEA), carotid artery
      stenting, endovascular aneurysm repair, open abdominal aortic aneurysms (AAA)
      repair and lower extremities vascular interventions. High-dose statin
      pretreatment is recommended for PCI and CABG according to current guidelines.
      Statin discontinuation should be avoided during acute cardiovascular events and
      vascular interventions; adequate measures should be implemented to overcome
      statin intolerance. SUMMARY: Statin loading is an important clinical issue in
      patients with cardiac and noncardiac vascular diseases, including carotid artery
      disease, peripheral artery disease and AAA, undergoing vascular interventions.
      Cardiologists and vascular surgeons should be aware of current evidence and
      implement guidelines in relation to statin loading, discontinuation and
      intolerance.

PMID- 29601329
TI  - HIV infection and lipids.
AB  - PURPOSE OF REVIEW: We comment on the role of dyslipidaemia in cardiovascular
      disease (CVD) in HIV-infected patients. We have discussed various risk factors,
      including traditional CVD risk factors, HIV-related risk factors and
      antiretroviral therapy (ART)-induced dyslipidaemia. RECENT FINDINGS: HIV-infected
      individuals are prone to lipid and lipoprotein abnormalities as a result of the
      infection itself and the effect of ART. The older drugs used for the treatment of
      HIV were associated with an increased risk of these abnormalities. New therapies
      used to treat HIV are lipid friendly. Calculating CVD risk in the HIV population
      is complex due to the infection itself and the ART-related factors. The
      advancement in ART has helped to increase the life expectancy of HIV patients. As
      a result, a growing number of patients die of non-HIV related complications such
      as CVD, hepatic and renal disease. Outcome studies with intervention for
      dyslipidaemia in HIV are underway. SUMMARY: The implications of the above
      findings suggest that all patients with HIV should undergo a CVD risk assessment
      before starting ART. Appropriate lipid-friendly ART regimen should be initiated
      along with intervention for associated CVD risk factors (e.g. lipids,
      hypertension and smoking).

PMID- 29601330
TI  - Introduction: Liquid Biopsies.

PMID- 29601332
TI  - Extracellular Vesicles in Cancer: Purpose and Promise.
AB  - Extracellular vesicles refer collectively to a heterogeneous group of membrane
      bound vesicles released from cells and loaded with bioactive proteins, nucleic
      acids, and lipids. The concept of extracellular vesicles has rapidly evolved from
      once being viewed as cellular debris to their recognition as packets of cellular
      information with considerable promise for clinical applications as biomarker
      platforms and therapeutic vehicles. These shed vesicles have emerged as critical
      mediators of intercellular communication in both local and distant
      microenvironments during normal physiological processes, as well as in
      orchestrating systemic pathophysiological events in disease. This mode of
      cellular crosstalk is particularly relevant to modulating the tumor
      microenvironment and orchestrating paths of least resistance during metastases.
      Here, we describe recent advances for the roles of extracellular vesicles in
      tumor progression and their potential as disease biomarkers.

PMID- 29601331
TI  - Implementing Liquid Biopsies in Clinical Trials: State of Affairs, Opportunities,
      and Challenges.
AB  - A primary goal of personalized medicine is to develop tumor-specific biomarkers
      to aid in treatment selection and to better evaluate response to targeted
      therapies. The assessment of circulating blood markers as surrogate real-time
      biopsies of disease status, termed liquid biopsies, has been under investigation.
      There are many different types of liquid biopsies each with different
      functionalities and limitations. These include tumor markers, circulating tumor
      cells, cell-free DNA, and extracellular vesicles including exosomes. Multiple
      clinical trials have evaluated liquid biopsies as prognostic biomarkers with
      positive results. Additional studies are underway to evaluate liquid biopsies as
      predictive biomarkers, pharmacodynamic biomarkers, and surrogate efficacy
      endpoints for treatment response evaluation. There are several challenges in and
      barriers to implementation of liquid biopsies into clinical trials and
      subsequently into routine clinical practice, which are addressed in this review.

PMID- 29601334
TI  - Liquid Biopsies and Cancer Immunotherapy.
AB  - Cancer immunotherapy has recently undergone rapid advances and has become an
      integral part of the treatment armamentarium in various malignancies. However,
      tissue-based biomarker development in this arena has been slow, and valid
      biomarker identification to guide immunotherapeutic management is desperately
      needed. "Liquid" or blood-based biopsies potentially offer more convenient and
      efficient means to judge the immune milieu of individual patients and identify
      who will benefit most from immunotherapy. The following review highlights the
      current literature regarding the application of liquid biopsies to cancer
      immunotherapy.

PMID- 29601333
TI  - Circulating Tumor Cells: Strategies for Capture, Analyses, and Propagation.
AB  - Circulating tumor cells (CTCs) play a central role in tumor dissemination and
      metastases, which are ultimately responsible for most cancer deaths. Technologies
      that allow for identification and enumeration of rare CTC from cancer patients'
      blood have already established CTC as an important clinical biomarker for cancer
      diagnosis and prognosis. Indeed, current efforts to robustly characterize CTC as
      well as the associated cells of the tumor microenvironment such as circulating
      cancer associated fibroblasts (cCAF), are poised to unmask key insights into the
      metastatic process. Ultimately, the clinical utility of CTC will be fully
      realized once CTC can be reliably cultured and proliferated as a biospecimen for
      precision management of cancer patients, and for discovery of novel therapeutics.
      In this review, we highlight the latest CTC capture and analyses technologies,
      and discuss in vitro strategies for culturing and propagating CTC.

PMID- 29601335
TI  - Mechanosensitive Ion Channels: TRPV4 and P2X7 in Disseminating Cancer Cells.
AB  - Cancer metastasis is the second leading cause of death in the United States.
      Despite its morbidity, metastasis is an inefficient process that few cells can
      survive. However, cancer cells can overcome these metastatic barriers via
      cellular responses to microenvironmental cues, such as through
      mechanotransduction. This review focuses on the mechanosensitive ion channels
      TRPV4 and P2X7, and their roles in metastasis, as both channels have been shown
      to significantly affect tumor cell dissemination. Upon activation, these channels
      help form tumor neovasculature, promote transendothelial migration, and increase
      cell motility. Conversely, they have also been linked to forms of cancer cell
      death dependent upon levels of activation, implying the complex functionality of
      mechanosensitive ion channels. Understanding the roles of TRPV4, P2X7 and other
      mechanosensitive ion channels in these processes may reveal new possible drug
      targets that modify channel function to reduce a tumor's metastatic potential.

PMID- 29601336
TI  - Molecular Profiling of Liquid Biopsy Samples for Precision Medicine.
AB  - In the context of oncology, liquid biopsies consist of harvesting cancer
      biomarkers, such as circulating tumor cells, tumor-derived cell-free DNA, and
      extracellular vesicles, from bodily fluids. These biomarkers provide a source of
      clinically actionable molecular information that can enable precision medicine.
      Herein, we review technologies for the molecular profiling of liquid biopsy
      markers with special emphasis on the analysis of low abundant markers from mixed
      populations.

PMID- 29601338
TI  - Evolving understanding of neonatal necrotizing enterocolitis.
AB  - PURPOSE OF REVIEW: Necrotizing enterocolitis (NEC) is a devastating disease that
      predominately affects premature neonates. The pathogenesis of NEC is
      multifactorial and poorly understood. Risk factors include low birth weight,
      formula-feeding, hypoxic/ischemic insults, and microbial dysbiosis. This review
      focuses on our current understanding of the diagnosis, management, and
      pathogenesis of NEC. RECENT FINDINGS: Recent findings identify specific mucosal
      cell types as potential therapeutic targets in NEC. Despite a broadly accepted
      view that bacterial colonization plays a key role in NEC, characteristics of
      bacterial populations associated with this disease remain elusive. The use of
      probiotics such as lactobacilli and bifidobacteria has been studied in numerous
      trials, but there is a lack of consensus regarding specific strains and dosing.
      Although growth factors found in breast milk such as epidermal growth factor and
      heparin-binding epidermal growth factor may be useful in disease prevention,
      developing new therapeutic interventions in NEC critically depends on better
      understanding of its pathogenesis. SUMMARY: NEC is a leading cause of morbidity
      and mortality in premature neonates. Recent data confirm that growth factors and
      certain bacteria may offer protection against NEC. Further studies are needed to
      better understand the complex pathogenesis of NEC.

PMID- 29601337
TI  - Future of Liquid Biopsies With Growing Technological and Bioinformatics Studies:
      Opportunities and Challenges in Discovering Tumor Heterogeneity With Single-Cell
      Level Analysis.
AB  - Liquid biopsy provides minimally invasive and readily obtainable access to tumor
      associated biological material in blood or other body fluids. These samples
      provide important insights into cancer biology, such as primary tumor
      heterogeneity; real-time tumor evolution; response to therapy, including
      immunotherapy; and mechanisms of cancer metastasis. Initial biological materials
      studied were circulating tumor cells and circulating nucleic acids, including
      circulating tumor DNA and microRNAs; more recently, studies have expanded to
      investigate extracellular vesicles, such as exosomes, microvesicles, and large
      oncosomes; tumor-derived circulating endothelial cells; and tumor-educated
      platelets. Even with an ongoing ambitious investment effort to develop liquid
      biopsy as an early cancer detection test in asymptomatic individuals, current
      challenges remain regarding how to access and analyze rare cells and tumor
      derived nucleic acids in cancer patients. Technologies and associated
      bioinformatics tools are continuously evolving to capture these rare materials in
      an unbiased manner and to analyze them with high confidence. After first
      presenting recent applications of liquid biopsy, this review discusses aspects
      affecting the field, including tumor heterogeneity, single-cell analyses, and
      associated computational tools that will shape the future of liquid biopsy, with
      resultant opportunities and challenges.

PMID- 29601339
TI  - The Role of the Electronic Medical Record in the Intensive Care Unit Nurse's
      Detection of Patient Deterioration: A Qualitative Study.
AB  - Failure to detect patient deterioration signals leads to longer stays in the
      hospital, worse functional outcomes, and higher hospital mortality rates.
      Surveillance, including ongoing acquisition, interpretation, and synthesis of
      patient data by the nurse, is essential for early risk detection. Electronic
      medical records promote accessibility and retrievability of patient data and can
      support patient surveillance. A secondary analysis was performed on interview
      data from 24 intensive care unit nurses, collected in a study that examined
      factors influencing nurse responses to alarms. Six themes describing nurses' use
      of electronic medical record information to understand the patients' norm and
      seven themes describing electronic medical record design issues were identified.
      Further work is needed on electronic medical record design to integrate
      documentation and information presentation with the nursing workflow.
      Organizations should involve bedside nurses in the design of handoff formats that
      provide key information common to all intensive care unit patient populations, as
      well as population-specific information.

PMID- 29601340
TI  - Missing Voices: Profile, Extent, and 12-Month Outcomes of Nonfatal Traumatic
      Brain Injury in Aboriginal and Non-Aboriginal Adults in Western Australia Using
      Linked Administrative Records.
AB  - OBJECTIVE: To investigate differences in the profile and outcomes between
      Aboriginal and non-Aboriginal Western Australians (WAs) hospitalized with
      traumatic brain injury (TBI). SETTING: WA hospitals. PARTICIPANTS: TBI cases aged
      15 to 79 years surviving their first admission during 2002-2011. DESIGN: Patients
      identified from diagnostic codes and followed up for 12 months or more using WA
      wide person-based linked hospital and mortality data. MAIN MEASURES: Demographic
      profile, 5-year comorbidity history, injury mechanism, injury severity, 12-month
      readmission, and mortality risks. Determinants of 12-month readmission. RESULTS:
      Of 16 601 TBI survivors, 14% were Aboriginal. Aboriginal patients were more
      likely to be female, live remotely, and have comorbidities. The mechanism of
      injury was an assault in 57% of Aboriginal patients (vs 20%) and transport in 33%
      of non-Aboriginal patients (vs 17%), varying by remoteness. One in 10 Aboriginal
      TBI patients discharged themselves against medical advice. Crude 12-month
      readmission but not mortality risk was significantly higher in Aboriginal
      patients (48% vs 36%). The effect of age, sex, and injury mechanism on 12-month
      readmission was different for Aboriginal and non-Aboriginal patients. CONCLUSION:
      These findings suggest an urgent need for multisectoral primary prevention of
      TBI, as well as culturally secure and logistically appropriate medical and
      rehabilitation service delivery models to optimize outcomes.

PMID- 29601341
TI  - Informant Report of Financial Capacity for Individuals With Chronic Acquired
      Brain Injury: An Assessment of Informant Accuracy.
AB  - OBJECTIVE: Primarily, to investigate the association between informant report and
      objective performance on specific financial capacity (FC) tasks by adults with
      chronic, moderate to severe acquired brain injury, and to examine the nature of
      misestimates by the informants. DESIGN: Cross-sectional design. SETTING: A
      postacute, community-based rehabilitation center. PARTICIPANTS: Data were
      obtained from 22 chronic acquired brain injury (CABI) adults, mean age of 46.6
      years (SD = 8.67), mean years of education of 13.45 years (SD = 2.15), with
      moderate to severe acquired brain injury (86% had traumatic brain injury), with a
      mean postinjury period of 17.14 years (SD = 9.5). Whereas the CABI adults
      completed the Financial Competence Assessment Inventory interview-a combination
      of self-report and performance-based assessment, 22 informants completed a
      specifically designed parallel version of the interview. RESULTS: Pearson
      correlations and 1-sample t tests based on the discrepancy scores between
      informant report and CABI group's performance were used. The CABI group's
      performance was not associated with its informant's perceptions. One-sample t
      tests revealed that informants both underestimated and overestimated CABI group's
      performance. CONCLUSIONS: Results indicate lack of correspondence between self-
      and informant ratings. Further investigation revealed that misestimations by
      informants occurred in contrary directions with CABI adults' performance being
      inaccurately rated. These findings raise critical issues related to assuming that
      the informant report can be used as a "gold standard" for collecting functional
      data related to financial management, and the idea that obtaining objective data
      on financial tasks may represent a more valid method of assessing financial
      competency in adults with brain injury.

PMID- 29601342
TI  - The Association of Rehospitalization With Participation 5 Years After Traumatic
      Brain Injury.
AB  - OBJECTIVE: To determine whether rehospitalization during the first 2 years after
      moderate to severe traumatic brain injury (TBI) is associated with poor
      participation at 5 years post-TBI, after controlling for demographic and severity
      factors. SETTING: TBI Model Systems Program. PARTICIPANTS: Community-dwelling
      individuals with TBI, 16 years or older (n = 1940). DESIGN: Retrospective data
      analysis of a multicenter prospective study. MAIN MEASURES: Participation
      Assessment with Recombined Tools-Objective (PART-O). RESULTS: After controlling
      for demographic and severity factors, a general linear model indicated that
      rehospitalization status (ie, never rehospitalized during years 1 and 2,
      rehospitalized either during year 1 or 2, or rehospitalized during both years 1
      and 2) predicted less participation at 5 years post-TBI (P = .0353). The PART-O
      scores were in the hypothesized direction, with the lowest covariate-adjusted
      mean participation score found for the group with rehospitalizations during both
      years and the highest covariate-adjusted mean participation score found in the
      group with no rehospitalizations. Examining total number of rehospitalizations
      during years 1 and 2, rather than rehospitalization status, yielded analogous
      results (P = .0148). CONCLUSIONS: This study suggests that rehospitalization in
      the first 2 years after TBI is negatively associated with participation at 5
      years after injury. Since participation is considered a key indicator of
      successful TBI rehabilitation, minimizing the need for rehospitalizations and
      promoting health in the community setting should be a priority of postacute care
      for individuals with TBI.

PMID- 29601343
TI  - A Preliminary Investigation of Accelerometer-Derived Sleep and Physical Activity
      Following Sport-Related Concussion.
AB  - OBJECTIVE: Describe changes in postconcussion activity levels and sleep
      throughout recovery in a sample of pediatric sport-related concussion (SRC)
      patients, and examine the predictive value of accelerometer-derived activity and
      sleep on subsequent clinical outcomes at a follow-up clinic visit. SETTING:
      Outpatient concussion clinic. PARTICIPANTS: Twenty athletes aged 12 to 19 years
      with diagnosed SRC. METHODS: Prospective study including visit 1 (<72 hours
      postinjury) and visit 2 (6-18 days postinjury). Linear regressions used to
      predict scores (ie, neurocognitive, vestibular/oculomotor) at visit 2 from
      accelerometer-derived data collected 0 to 6 days postinjury. Linear mixed models
      evaluated changes in activity and sleep across recovery. MAIN MEASURES: Symptom,
      neurocognitive, and vestibular/oculomotor scores; sleep and activity data
      (Actigraph GT3x+) RESULTS:: The maximum intensity of physical activity increased
      (P = .009) and time in bed decreased throughout recovery (P = .026). Several
      physical activity metrics from 0 to 6 days postinjury were predictive of worse
      vestibular/oculomotor scores at visit 2 (P < .05). Metrics indicative of poor
      sleep 0 to 6 days postinjury were associated with worse reaction time at visit 2
      (P < .05). CONCLUSIONS: This exploratory study suggests physical activity and
      sleep change from the acute to subacute postinjury time period in adolescent SRC
      patients. In our small sample, excess physical activity and poor sleep the first
      week postinjury may be associated with worse outcomes at follow-up in the
      subacute stage of recovery. This study further supported the feasibility of
      research utilizing wearable technology in concussion patients, and future
      research in a large, diverse sample of concussion patients examined at concise
      time intervals postinjury is needed.

PMID- 29601344
TI  - Effects of Web-Based Parent Training on Caregiver Functioning Following Pediatric
      Traumatic Brain Injury: A Randomized Control Trial.
AB  - OBJECTIVE: To examine the effects of a Web-based parenting intervention (I
      InTERACT), and an abbreviated version (Express), on caregiver depression,
      psychological distress, parenting stress, and parenting efficacy following
      pediatric traumatic brain injury (TBI). SETTING: Four children's hospitals and 1
      general hospital in the United States. PARTICIPANTS: 148 caregivers of 113
      children aged 3 to 9 years with a moderate to severe TBI. DESIGN: Multicenter
      randomized controlled trial. Participants were randomly assigned to I-InTERACT,
      Express, or an active control condition. Caregiver data were collected at
      baseline and postintervention (6 months later). INTERVENTION: I-InTERACT (10-14
      sessions) and Express (7 sessions) combine live coaching of parenting skills and
      positive parenting strategies. MAIN MEASURES: Center for Epidemiologic Studies
      Depression Scale (CES-D); Global Severity Index of the Symptom Checklist-90-R
      (GSI), Parenting Stress Index (PSI), and Caregiver Self-Efficacy Scale (CSES).
      RESULTS: Analyses revealed no main effects of treatment on caregiver distress
      (GSI), parenting stress (PSI), or parenting efficacy (CSES). However, analyses
      examining baseline severity as a moderator found that caregivers with elevated
      levels of depression in I-InTERACT experienced significantly greater reductions
      in CES-D scores compared with caregivers in the active control condition.
      CONCLUSIONS: I-InTERACT reduced caregiver depression but no other facets of
      caregiver psychological functioning. Modifications to the treatment content may
      be necessary to reduce parenting stress and improve caregiver efficacy.

PMID- 29601345
TI  - Family Needs on an Inpatient Brain Injury Rehabilitation Unit: A Quantitative
      Assessment.
AB  - OBJECTIVE: To examine the needs of family members in an inpatient setting and
      factors predicting extent to which needs are perceived as met. SETTING:
      University health system inpatient rehabilitation unit. PARTICIPANTS: Adult
      survivors of traumatic brain injury and family members (n = 85). DESIGN:
      Prospective, cross-sectional. MAIN MEASURE: Family Needs Questionnaire-Revised
      (FNQ-R). RESULTS: Needs related to the Health Information subscale were most
      frequently rated as met, whereas needs related to the Instrumental Support and
      Emotional Support subscales were most frequently rated as unmet. Predictors
      related to the FNQ-R included family income, gender, and ethnicity. For 4 of 6
      subscales, white family members were more likely to rate needs as unmet than
      minority members. For 3 subscales, females were more likely to rate needs as
      unmet than males. Greater household income was associated with fewer met needs
      for 2 subscales. CONCLUSIONS: The ranking of met and unmet needs in the present
      study was remarkably similar to previous studies within and outside the United
      States. Clinicians should not assume that families with relatively higher incomes
      will experience fewer unmet needs. Through structured assessment, clinicians can
      reveal perceived needs that might have otherwise been unrecognized and facilitate
      appropriate supports. Findings provide direction for inpatient program
      development.

PMID- 29601346
TI  - Low Bone Mineral Density in Elite Female Athletes With a History of Secondary
      Amenorrhea in Their Teens.
AB  - OBJECTIVE: To determine whether secondary amenorrhea during teenage years
      influences bone mineral density (BMD) in female athletes in their 20s. DESIGN:
      Original research. SETTING: Japan Institute of Sports Sciences. PARTICIPANTS: Two
      hundred ten elite female athletes older than 20 years were included in the study.
      MAIN OUTCOME MEASURES: Information on the participants' past (ie, during their
      teenage years) and current menstrual cycle, training time, history of stress
      fractures, and blood tests for hormones received was obtained. Bone mineral
      density of the lumbar spine was evaluated by dual-energy x-ray absorptiometry;
      low BMD was defined as a Z-score <=-1. We investigated the correlation factors
      for low BMD in athletes in their 20s by univariable and multivariable logistic
      regression analysis. RESULTS: A total of 39 (18.6%) female athletes had low BMD.
      Secondary amenorrhea in their teens [odds ratio (OR), 7.11, 95% confidence
      interval (CI), 2.38-21.24; P < 0.001] and present body mass index (BMI) (OR,
      0.56, 95% CI, 0.42-0.73; P < 0.001) were independent correlation factors for low
      BMD in the multivariable logistic regression analysis. The average Z-score for
      those with secondary amenorrhea in their teens and 20s, secondary amenorrhea in
      their 20s only, and regular menstruation was -1.56 +/- 1.00, -0.45 +/- 1.21, and
      0.82 +/- 1.11 g/cm, respectively. CONCLUSIONS: Secondary amenorrhea for at least
      1 year during teenage years in female athletes and BMI at present was strongly
      associated with low BMD in their 20s.

PMID- 29601347
TI  - Test-Retest Reliability and the Effects of Exercise on the King-Devick Test.
AB  - OBJECTIVE: To determine the test-retest reliability and the influence of exercise
      on King-Devick (K-D) test performance. DESIGN: Crossover study design. SETTING:
      Controlled laboratory. PARTICIPANTS: Participants consisted of 63 (39 women and
      24 men) healthy, recreationally active college students who were 21.0 + 1.5 years
      of age. INDEPENDENT VARIABLES: Participants completed the K-D test using a 2
      week, test-retest interval. The K-D test was administered before and after a
      counterbalanced exercise or rest intervention. Reliability was assessed using
      testing visits (visit 1 and visit 2) as the independent variables. Exercise or
      rest and time (baseline, postintervention) were used as independent variables to
      examine the influence of exercise. MAIN OUTCOME MEASURES: Intraclass correlation
      (ICC) coefficients with 95% confidence intervals were calculated between visits
      to assess reliability of K-D test completion time. A repeated-measure 2 x 2
      analysis of variance (intervention * time) with post hoc paired t tests was used
      to assess the influence of exercise on K-D test performance. RESULTS: The K-D
      test was observed to have strong test-retest reliability [ICC2,1 = 0.90 (0.71,
      0.96)] over time. No significant intervention-by-time interaction (P = 0.55) or
      intervention main effects (P = 0.68) on K-D time were observed. Mean differences
      of -1.5 and -1.7 seconds (P < 0.001) were observed between baseline and rest and
      exercise interventions for K-D test performance, respectively. Up to 32% (20/63)
      of participants were observed to have a false-positive K-D test performance
      before and after each intervention. CONCLUSIONS: Although strong test-retest
      reliability coefficients were observed using clinically relevant time points, a
      high false-positive rate warrants caution when interpreting the K-D test.

PMID- 29601348
TI  - Association Between a Physical Activity Vital Sign and Cardiometabolic Disease in
      High-Risk Patients.
AB  - OBJECTIVE: To determine the association between the physical activity vital sign
      (PAVS) and markers of cardiometabolic disease. DESIGN: Patients were assessed
      through the PAVS, a validated tool self-reporting the frequency and duration of
      physical activity. Patients were categorized into 3 groups: inactive (0 minutes
      per week), underactive (1-149 minutes per week), and active (>150 minutes per
      week). Associations were tested between the PAVS and the cardiometabolic disease
      biomarkers of body mass index, hemoglobin A1c (A1c), blood pressure, and low
      density lipoprotein (LDL) using one-way analyses of variance. SETTING: High-risk
      family medicine residency clinic. PARTICIPANTS: Two thousand three hundred twenty
      one adult patients (age >= 18 years). RESULTS: Participants reported a mean of
      97.87 (SD = 149.35) minutes per week of exercise. Overall, 50.1% reported
      physical inactivity, 25.7% were underactive, and 24.3% were active. Younger
      individuals (P < 0.001) and men (P < 0.05) reported more physical activity than
      older individuals and women. Patients who reported being active were
      significantly less likely to be overweight (P < 0.05), obese (P < 0.05), or
      hypertensive (P < 0.05), but there was no association with A1c or LDL levels.
      CONCLUSIONS: This is the first investigation to examine the PAVS in a high-risk
      population. In these patients, reported levels of physical inactivity are 150%
      higher than other clinical settings, and the PAVS is only associated with
      improvements in 2 of 4 major cardiometabolic risk factors. For this group, self
      reported levels of physical activity may need to be higher for cardiovascular
      benefits to be realized in all 4 cardiometabolic domains. The PAVS offers health
      professionals an opportunity to encourage lifestyle-based interventions to reduce
      cardiovascular risk, but refinements may be necessary to address this population.

PMID- 29601349
TI  - Factors Associated With Self-Reported Concussion History in Middle School
      Athletes.
AB  - OBJECTIVE: Identifying personal characteristics associated with sustaining a
      concussion is of great interest, yet only a few have examined this in children.
      The purpose of this study was to examine the association between sex,
      neurodevelopmental disorders, health history, and lifetime history of self
      reported concussion in 12- and 13-year-old athletes. DESIGN: Cross-sectional
      study. SETTING: Middle schools. PARTICIPANTS: Participants were 1744 twelve- and
      thirteen-year-old student athletes who completed preseason Immediate Post
      Concussion Assessment and Cognitive Testing (ImPACT) testing, including a self
      report questionnaire about previous concussions, developmental diagnoses, and
      previous medical treatment. INDEPENDENT VARIABLES: Age, sex, attention
      deficit/hyperactivity disorder (ADHD), learning disabilities (LDs), and previous
      treatment for migraine. MAIN OUTCOME MEASURES: Self-reported history of
      concussion. RESULTS: A minority of athletes (13.7%) reported previous concussions
      (1 concussion, n = 181; 2 concussions, n = 41; and 3+ concussions, n = 17). A
      small proportion reported a history of ADHD (4.4%), LD (2.8%) or migraine
      treatment (4.0%). Higher rates of self-reported previous concussions were
      associated with male sex (16.9% vs 9.1%; chi(1) = 21.47, P < 0.001) and previous
      migraine treatment (31.9% vs 13.0%; chi(1) = 20.08, P < 0.001). There were no
      differences in self-reported concussion history between 12- and 13-year olds (P =
      0.18) and those with/without ADHD (P = 0.41) or LDs (P = 0.06). The overall
      logistic regression model was statistically significant (chi(5) = 42.01, P <
      0.001) but explained only 4.3% of the variance. Previous treatment for migraine
      (P < 0.001, Exp(B) = 3.30) and male sex (P < 0.001, Exp(B) = 2.06) were
      independently associated with a self-reported concussion history, whereas age,
      LD, and ADHD were not (P's > 0.05). CONCLUSIONS: Male sex and previous migraine
      treatment were associated with higher rates of self-reported previous concussions
      in both independent and multivariate models in middle school athletes, whereas
      age, ADHD, and LDs were not.

PMID- 29601350
TI  - In Response to: Impact of CrossFit-Related Spinal Injuries.

PMID- 29601351
TI  - How to predict and improve prognosis of food allergy.
AB  - PURPOSE OF REVIEW: The prevalence of food allergy is increasing. More children
      are being diagnosed with food allergies, and it is taking longer to outgrow them,
      among those who develop tolerance. The aim of this review is to draw the profile
      of the persistent food allergic, so that prevention strategies can be developed
      and active treatment set up. RECENT FINDINGS: Many determinants are involved in
      food allergy prognosis: ethnicity and sex, type of food, innate immune system,
      eliciting dose, sensitization status and other biomarkers determination, gut
      microbiome composition, and the presence of comorbidities. Once identified, a
      persistent food allergy could be conveyed to active treatments, such as oral
      immunotherapy or the use of biologics, always taking into account their
      experimental nature. SUMMARY: A better understanding of prognostic factors and
      phenotypes of food allergy is crucial in decision-making when it comes to food
      allergy prevention and management. A good classification of the allergic patient
      allows to determine the degree of exclusion diets and the timing of the
      reintroduction of avoided food when possible. In the cases of persistent and
      severe food allergy, many promising interventions are emerging which could
      improve prognosis and quality of care.

PMID- 29601352
TI  - Avenues for research in food allergy prevention: unheeded ideas from the
      epidemiology.

PMID- 29601353
TI  - How to diagnose food allergy.
AB  - PURPOSE OF REVIEW: To assess the recent studies that focus on specific
      immunoglobulin E (sIgE) testing and basophil activation test (BAT) for diagnosing
      IgE-mediated food allergies. RECENT FINDINGS: The sIgE to allergen extract or
      component can predict reactivity to food. The cutoff value based on the positive
      predictive value (PPV) of sIgE can be considered whenever deciding whether oral
      food challenge (OFC) is required to diagnose hen's egg, cow's milk, wheat,
      peanut, and cashew nut allergy. However, PPV varies depending on the patients'
      background, OFC methodology, challenge foods, and assay methodology. Component
      resolved diagnostics (CRD) has been used for food allergy diagnosis. Ovomucoid
      and omega-5 gliadin are good diagnostic markers for heated egg and wheat allergy.
      More recently, CRD of peanut, tree nuts, and seed have been investigated. Ara h 2
      showed the best diagnostic accuracy for peanut allergy; other storage proteins,
      such as Jug r 1 for walnut, Ana o 3 for cashew nut, Ses i 1 for sesame, and Fag e
      3 for buckwheat, are also better markers than allergen extracts. Some studies
      suggested that BAT has superior specificity than skin prick test and sIgE
      testing. SUMMARY: The sIgE testing and BAT can improve diagnostic accuracy. CRD
      provides additional information that can help determine whether OFCs should be
      performed to diagnose food allergy.

PMID- 29601354
TI  - Phenotypes/endotypes-driven treatment in asthma.
AB  - PURPOSE OF REVIEW: Target therapy is the necessary step towards personalized
      medicine. The definition of asthma phenotypes and underlying mechanisms
      (endotypes) represent a key point in the development of new asthma treatments.
      Big data analysis, biomarker research and the availability of monoclonal
      antibodies, targeting specific cytokines is leading to the rapid evolution of
      knowledge. In this review, we sought to outline many of the recent advances in
      the field. RECENT FINDINGS: Several attempts have been made to identify asthma
      phenotypes, sometimes with contrasting results. More success has been obtained
      concerning the pathogenetic mechanism of specific asthma patterns with the
      consequent identification of biomarkers and development of effective ad hoc
      treatment. SUMMARY: We are in the middle of an extraordinary revolution of our
      mode of thinking about and approaching asthma. All the effort in the
      identification of clusters of patients with different disease clinical patterns,
      prognosis and response to treatment is closely linked to the identification of
      endotypes (Th2-low and Th2-high). This approach has allowed the development of
      the specific treatments (anti IgE, Anti IL5 and IL5R) that are now available and
      is leading to new ones.

PMID- 29601355
TI  - How to prevent food allergy during infancy: what has changed since 2013?
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent studies and
      emerging consensus guidelines regarding food allergy prevention in infants of the
      past 5 years. RECENT FINDINGS: Prior to 2013, the general consensus regarding
      prevention of food allergy in infants was to recommend delayed introduction or
      complete avoidance of commonly allergenic foods, such as milk, egg and peanut.
      However, in the past 5 years, several landmark studies have been conducted,
      particularly with peanut. The results of these studies have led to a paradigm
      shift from recommending delayed introduction to early introduction and frequent
      feeding of highly allergenic foods such as peanut, with hopes of achieving
      primary and secondary prevention of food allergy in infants. SUMMARY: Recent
      clinical trials have demonstrated that early introduction and frequent feeding,
      rather than delayed introduction or complete avoidance, of commonly allergenic
      foods plays a critical role in preventing food allergy in infants. More studies
      are required to risk-stratify infants by personal and family atopic history to
      tailor guidelines for groups with inherently different risks. The universal
      acceptance of the guidelines and their application outcome are still to be
      determined.

PMID- 29601356
TI  - Current opinion in allergy and clinical immunology: a change in leadership.

PMID- 29601357
TI  - Application of precision medicine to the treatment of anaphylaxis.
AB  - PURPOSE OF REVIEW: Recognize the presentation of anaphylaxis for prompt
      management and treatment and to provide tools for the diagnosis of the underlying
      cause(s) and set up a long-term treatment to prevent recurrence of anaphylaxis.
      RECENT FINDINGS: The recent description of phenotypes provides new insight and
      understanding into the mechanisms and causes of anaphylaxis through a better
      understanding of endotypes and biomarkers for broad clinical use. SUMMARY:
      Anaphylaxis is the most severe hypersensitivity reaction and can lead to death.
      Epinephrine is the first-line treatment of anaphylaxis and it is life-saving.
      Patients with first-line therapy-induced anaphylaxis are candidates for
      desensitization to increase their quality of life and life expectancy.
      Desensitization is a breakthrough novel treatment for patients with anaphylaxis
      in need of first-line therapy, including chemotherapy, mAbs, aspirin and others.
      Ultrarush with venom immunotherapy should be considered in patients who present
      with life-threatening anaphylaxis after Hymenoptera sting with evidence of IgE
      mediated mechanisms. Food desensitization is currently being expanded to provide
      increased safety to adults and children with food-induced anaphylaxis.

PMID- 29601358
TI  - A Meta-analysis of the Association Between Physical Activity and Breast Cancer
      Mortality.
AB  - BACKGROUND: There are conflicting data on the association between physical
      activity (PA) intensity and amount and prognosis of breast cancer. It is unknown
      whether increasing or decreasing PA is associated with all-cause mortality.
      OBJECTIVE: The purpose of this study was to estimate the associations between PA
      and the risk of mortality. METHODS: MEDLINE and EMBASE were used to find eligible
      studies published from January 1970 to March 2017 for this meta-analysis. We
      included 24 studies, with a total of 144 224 patients and follow-up periods
      ranging from 1.9 to 12.7 years. We categorized the amount of PA as low (<300
      min/wk), moderate (300-500 min/wk), and high (>500 min/wk). RESULTS: We found
      that high amounts of PA had an inverse relationship with breast-cancer-specific
      mortality and all-cause morality. Patients who decreased PA after diagnosis
      showed poorer all-cause mortality, whereas patients who increased PA
      postdiagnosis had a favorable association with all-cause mortality. Last,
      patients who met PA guidelines after diagnosis had a lower breast-cancer-specific
      mortality and all-cause mortality. CONCLUSION: Physical activity may play a
      pivotal role in reducing the risk of death. Getting at least 300 min/wk of
      moderate-intensity PA will help improve the risk of breast cancer death.
      IMPLICATIONS FOR PRACTICE: Participating in PA is an essential factor in breast
      cancer care that extends throughout the life span of cancer survivors. Higher
      levels of PA than current PA guidelines should be recommended to cancer patients.

PMID- 29601359
TI  - Representations of Young Cancer Survivorship: A Discourse Analysis of Online
      Presentations of Self.
AB  - BACKGROUND: More young people are surviving treatment for cancer than ever
      before. Survival can have an adverse impact on their transition to adulthood.
      Discourses of cancer are applied to cancer survivors of all ages, but they
      manifest differently for young people. OBJECTIVE: The aim of this study was to
      describe practices of self-representation in an online Web site that supports
      young Australian cancer survivors. METHOD: We conducted a discourse analysis of
      images and text produced by young cancer survivors (aged 18-35 years) on a public
      cancer charity Web site. RESULTS: The dominant subject position of participants
      published on this web site is one of empowered, beautiful cancer survivor. This
      applies to young people who have learned to embrace their cancer as providing a
      positive influence on their lives. However, this discourse can marginalize those
      whose cancer experience remains a source of distress or shame. CONCLUSION: Web
      based media can provide a valuable forum for some young people to celebrate their
      cancer survival and to affirm the constructive influence that their cancer
      experience has had on their lives. However, we ponder the apparent unsuitability
      of some forums for young cancer survivors who have not yet found cause for
      celebration. IMPLICATIONS FOR PRACTICE: Nurses have the opportunity to contribute
      to the development of supportive structures that meet the specific needs of
      different groups of young cancer survivors. This might mean assisting young
      cancer survivors who are struggling to find meaning in their cancer experience to
      negotiate the establishment of a new normal that they can embrace.

PMID- 29601360
TI  - Using a Patient-Centered Approach to Identify Symptom Clusters Among Adolescents
      With Cancer.
AB  - BACKGROUND: Prior studies identifying symptom clusters used a symptom-centered
      approach to demonstrate the relationship among symptoms. Latent profile analysis
      (LPA) is a patient-centered approach that classifies individuals from a
      heterogeneous population into homogeneous subgroups, helping prioritize
      interventions to focus on clusters with the most severe symptom burden.
      OBJECTIVE: The aim of this study was to use LPA to determine the best-fit models
      and to identify phenotypes of severe symptom distress profiles for adolescents
      with cancer who are undergoing treatment and in survivorship. METHODS: We used
      estimated means generated by the LPA to predict the probability of an individual
      symptom occurring across on- and off-treatment groups for 200 adolescents with
      cancer. RESULTS: The 3-profile solution was considered the best fit to the data
      for both on- and off-treatment groups. Adolescents on treatment and classified
      into the severe profile were most likely to report distress in appetite, fatigue,
      appearance, nausea, and concentration. Adolescents off treatment and classified
      into the severe profile were most likely to report distress in fatigue, pain
      frequency, and concentration. CONCLUSIONS: Latent profile analysis provided a
      cluster methodology that uncovered hidden profiles from observed symptoms. This
      made it possible to directly compare the phenotypes of severe profiles between
      different treatment statuses. IMPLICATIONS FOR PRACTICE: The co-occurring 13-item
      Symptom Distress Scale symptoms found in the severe symptom distress profiles
      could be used as items in a prespecified severe symptom distress cluster, helping
      evaluate a patient's risk of developing varying degrees of symptom distress.

PMID- 29601361
TI  - How Interdisciplinary Teamwork Contributes to Psychosocial Cancer Support.
AB  - BACKGROUND: The organization of psychosocial care is rather complex, and its
      provision diverse. Access is affected by the acceptance and attitude of patients
      and professional caregivers toward psychosocial care. OBJECTIVES: The aims of
      this study were to examine when patients with cancer experience quality
      psychosocial care and to identify circumstances in collaboration that contribute
      to patient-perceived positive psychosocial care. METHODS: This study used a
      qualitative design in which semistructured interviews were conducted with
      patients, hospital workers, and primary health professionals. RESULTS:
      Psychosocial care is often requested but also refused by patients with cancer.
      Based on this discrepancy, a distinction is made between psychosocial support and
      psychosocial interventions. Psychosocial support aims to reduce the chaos in
      patients' lives caused by cancer and is not shunned by patients. Psychosocial
      interventions comprise the formal care offered in response to psychosocial
      problems. Numerous patients are reluctant to use psychosocial interventions,
      which are often provided by psychologists. CONCLUSION: Psychosocial care aims to
      assist patients in bearing the difficulties of cancer and its treatment. Patients
      prefer informal support, given often in conjunction with physical care.
      IMPLICATIONS FOR PRACTICE: This study confirms the important role of nurses in
      promoting psychosocial care. Patients perceive much support from nurses, although
      nurses are not considered to be professional psychosocial caregivers. Being
      perceived as approachable and trustworthy offers nurses a significant opportunity
      to bring more intense psychosocial interventions within reach of cancer patients.

PMID- 29601362
TI  - Roles of Family Caregivers and Perceived Burden When Caring for Hospitalized
      Adult Cancer Patients: Perspective From a Low-Income Country.
AB  - BACKGROUND: Family caregivers (FCGs) of adult cancer patients (ACPs) are
      typically involved in the entire trajectory of cancer disease, from diagnosis to
      survivorship or end of life. In developing countries, FCGs are more intensely
      involved in the process of providing care to the hospitalized ACPs because of
      lack of adequate cancer care resources. Active performance of tasks to meet the
      needs of ACPs in the hospital setting is likely to elicit significant caregiver
      burden. OBJECTIVE: The aim of this study was to explore the tasks performed and
      the caregiver burden experienced by FCGs of hospitalized ACPs in a sub-Saharan
      country. METHODS: A cross-sectional descriptive design was used to collect data
      from 168 FCGs of ACPs. The Caregiver Burden Scale was used to measure burden.
      RESULTS: The most common cancer diagnosis in male and female ACPs was Kaposi's
      sarcoma (32.1%) and breast cancer (37.9%), respectively. The tasks regularly
      performed by most FCGs for the ACPs were providing emotional support (79.8%),
      feeding (68.5%), transporting to other appointments (62.5%), preparing meals
      (55%), and giving medications (46.4%). Most FCGs (75%) were experiencing severe
      or very severe general caregiver burden. The dimensions of caregiver burden that
      were most severely impacted were general strain (70.6%), disappointment (85.8%),
      and isolation (72%). Predictors of caregiver burden are reported. CONCLUSION:
      Family caregivers of hospitalized ACPs experience severe caregiver burden. The
      main forms of burden experienced were general strain, disappointment, and
      isolation. IMPLICATIONS FOR PRACTICE: Cancer care services in developing
      countries should be strengthened with services that address FCGs' emotional needs
      and human resources to curtail the strain imposed on FCGs.

PMID- 29601363
TI  - Outcomes of Trabeculectomy and Glaucoma Drainage Devices for Elevated Intraocular
      Pressure After Penetrating Keratoplasty.
AB  - PURPOSE: To assess and compare the outcomes of trabeculectomy with and without
      antimetabolites (AMs) and glaucoma drainage devices (GDDs) in the management of
      elevated intraocular pressure (IOP) after penetrating keratoplasty (PK). METHODS:
      Data of 84 eyes of 81 patients who underwent trabeculectomy (12 eyes without an
      AM and 42 eyes with an AM) or GDD implantation (30 eyes) after PK were reviewed
      retrospectively. The main outcome measures were IOP control, corneal graft
      survival, and postoperative ocular complications. RESULTS: At the final visit,
      IOP success (<22 mm Hg) was 58.3% in trabeculectomy alone, 64.3% in
      trabeculectomy with an AM (TrabAM), and 86.7% in GDD groups (P = 0.047). The
      median time from surgery to IOP failure was 1 month after trabeculectomy alone,
      13 months after TrabAM, and 20 months after GDD implantation (P = 0.042). The
      cumulative probability of IOP success rates at 1 and 3 years postoperatively was
      as follows: 66.7% and 57.1% in trabeculectomy alone, 80.6% and 64.8% in TrabAM,
      and 92.3% and 84.6 in GDD groups (P = 0.063). The cumulative probability of
      corneal graft survival rates at 1 and 3 years postoperatively was as follows:
      70.0% and 60.0% in trabeculectomy alone, 76.7% and 67.7% in TrabAM, and 65.8% and
      52.6% in GDD groups (P = 0.549). CONCLUSIONS: GDDs are more successful than
      trabeculectomy in controlling IOP in eyes that have undergone PK, but they tend
      to have low corneal graft survival rates. Trabeculectomy without an AM has
      limited success and may be considered in a limited number of patients with a low
      risk for bleb failure.

PMID- 29601365
TI  - Adjuvant Use of Cyclosporine A in the Treatment of Primary Pterygium: A
      Systematic Review and Meta-Analysis.
AB  - PURPOSE: To evaluate the efficacy and tolerability of cyclosporine A (CsA) as an
      adjuvant treatment for primary pterygium. METHODS: A comprehensive literature
      search from 7 databases (EMBASE, ISI Web of Science, PubMed, and the Cochrane
      Library for studies published in English and VIP, Wan Fang, and CNKI for studies
      published in Chinese). For the recurrence rate, pooled odds ratio (OR) and 95%
      confidence interval (CI) were calculated using a random-effects model.
      Tolerability estimates were measured by OR for adverse events. RESULTS: A total
      of 7 studies meeting the inclusion criteria were included in this meta-analysis.
      Compared with the group with adjunctive CsA usage, the control group (no adjuvant
      use of CsA) showed a significantly increased risk of pterygium recurrence (OR =
      2.71; 95% CI, 1.62-4.54). No obvious heterogeneity was detected in the included
      studies. Subgroup analysis showed that adjuvant use of CsA with pterygium
      excision alone resulted in a significantly lower frequency of recurrence than was
      seen in the group without adjuvant use of CsA (OR = 3.16; 95% CI, 1.18-8.84).
      However, there is no significant difference in pterygium recurrence between the
      subgroup (CsA + pterygium excision + limbal conjunctival autograft or flap
      rotation) and the subgroup without adjunctive CsA usage (pterygium excision +
      limbal conjunctival autograft or flap rotation). CONCLUSIONS: This meta-analysis
      suggests that adjuvant use of CsA can significantly reduce the risk of pterygium
      recurrence compared with pterygium excision alone, whereas adjuvant use of CsA
      may not reduce the risk of pterygium recurrence in terms of pterygium excision +
      limbal conjunctival autograft or conjunctival flap rotation.

PMID- 29601364
TI  - Corneal Cross-Linking for Pediatric Keratcoconus Review.
AB  - PURPOSE: To comprehensively review the available published literature for cross
      linking in the pediatric population. METHODS: Review of the literature published
      in English in PubMed. RESULTS: Two hundred ten publications were considered. One
      hundred fifteen were considered relevant to this review. CONCLUSIONS: Studies of
      cross-linking in pediatric patients are sparse, with relatively short follow-up
      times, and mostly on small groups of patients. Treatment with cross-linking halts
      progression of keratoconus in the pediatric population, and early treatment seems
      to be cost-effective compared with later penetrating keratoplasty. Long-term
      effects and regression rates remain unclear, and further studies are needed in
      this population.

PMID- 29601366
TI  - Risk of Anterior Segment Complications Associated With the Live Herpes Zoster
      Vaccine: Evidence From a Health-Claim Database.
AB  - PURPOSE: To determine the risk of developing anterior segment complications after
      receiving the live herpes zoster virus vaccine. METHODS: This retrospective
      cohort study included a random sample of 9 million patients registered in a
      health-claim database in the United States between 2006 and 2016. Herpes zoster
      related anterior segment diseases were identified by International Classification
      of Diseases ninth or tenth edition codes (an event). Patients without any event
      before index dates were separated into cohorts 1 and 2. Cohort 1 received the
      live virus vaccine on the index date. Cohort 2 was diagnosed with nonophthalmic
      zoster on the index date. The recurrent cohorts consisted of those who had an
      event 6 months or more before the index dates and were separated into cohort 3
      and cohort 4 based on the same criteria as cohort 1 and 2, respectively. All
      cohorts were followed to the first event. Hazard ratios (HRs) of anterior segment
      complications after vaccine administration were determined. RESULTS: There were
      72,141 vaccine users and 133,604 nonusers. There were 379 events and 1032 events
      in cohort 1 and cohort 2, respectively. The adjusted HR was 0.89 (95% confidence
      interval: 0.77-1.02). Among those with recurrent disease, there were 2679 vaccine
      users and 9421 nonusers. There were 16 events in cohort 3, compared with 86
      events in cohort 4. The adjusted HR was 0.70 (95% confidence interval: 0.40
      1.23). CONCLUSIONS: Data from a large health-claim database suggest that the live
      zoster virus vaccine is not associated with a higher risk of anterior segment
      complications.

PMID- 29601368
TI  - Heart Failure Self-care Within the Context of Patient and Informal Caregiver
      Dyadic Engagement: A Mixed Methods Study.
AB  - BACKGROUND: Recent heart failure (HF) patient and informal caregiver (eg, dyadic)
      studies have either examined self-care from a qualitative or quantitative
      perspective. To date, the 2 types of data have not been integrated. OBJECTIVE:
      The aim of this study was to understand HF self-care within the context of dyadic
      engagement. METHODS: This was a cross-sectional, mixed methods
      (quantitative/qualitative) study. Heart failure self-care was measured with the
      Self-care of Heart Failure Index (v.6) dichotomized to adequate (>=70) or
      inadequate (<69). Dyadic symptom management type was assessed with the Dyadic
      Symptom Management Type scale. Interviews regarding self-care were conducted with
      both dyad members present. Content analytic techniques were used. Data were
      integrated using an information matrix and triangulated using Creswell and Plano
      Clark's methods. RESULTS: Of the 27 dyads, HF participants were 56% men, with a
      mean age of 77 years. Caregivers were 74% women, with a mean age of 66 years,
      representing spouses (n = 14) and adult children (n = 7). Quantitatively, few
      dyads scored as adequate (>=70) in self-care; the qualitative data described the
      impact of adequacy on the dyads' behavior. Dyads who scored higher, individually
      or both, on self-care self-efficacy and self-care management were less likely to
      change from their life course pattern. Either the patient or dyad continued to
      handle all self-care as they always had, rather than trying new strategies or
      reaching out for help as the patient's condition deteriorated. CONCLUSIONS: Our
      data suggest links that should be explored between dyadic adequacy and response
      to patients' symptoms. Future studies should assess dyadic adequacy
      longitudinally and examine its relationship to event-free survival and health
      services cost.

PMID- 29601369
TI  - Quality of Life for Parents of Children With Congenital Heart Defect: A
      Systematic Review.
AB  - BACKGROUND: As survival rates for infants born with severe forms of cardiac
      defects (congenital heart defect [CHD]) improve, attention is directed to
      evaluating factors that affect the child's short- and long-term outcomes
      including parental quality of life (QOL). PURPOSE: The purpose of this review was
      to identify how parental QOL is affected when having a child with a CHD. Factors
      that influence parental QOL when having a child with a CHD will also be
      described. METHODS: A systematic search of CINAHL, EMBASE, PsycINFO, and PubMed
      databases was performed. Thirty-three quantitative cross-sectional or cohort
      studies were selected for inclusion and analyzed for quality reporting using
      Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
      RESULTS: Heart defect severity, age of child, perceived support, and availability
      of economic resources were identified as factors affecting parental QOL. Parent
      gender was related to QOL and family functioning factors. Paternal outcomes were
      reported in 23 of the 33 studies (70%), with an average father participation rate
      of 40%. CONCLUSIONS: Having a child with CHD negatively affects parental QOL.
      Future research should include targeting fathers to improve understanding of
      their unique perceptions and needs. Longitudinal studies should also describe
      correlations of parental QOL with their child's developmental outcomes. Efficacy
      studies testing supportive interventions on outcomes such as improved adjustment
      and QOL are needed.

PMID- 29601367
TI  - Design and Rationale of the Cognitive Intervention to Improve Memory in Heart
      Failure Patients Study.
AB  - BACKGROUND: Memory loss is an independent predictor of mortality among heart
      failure patients. Twenty-three percent to 50% of heart failure patients have
      comorbid memory loss, but few interventions are available to treat the memory
      loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate
      efficacy of computerized cognitive training intervention using BrainHQ to improve
      primary outcomes of memory and serum brain-derived neurotrophic factor levels and
      secondary outcomes of working memory, instrumental activities of daily living,
      and health-related quality of life among heart failure patients; (2) evaluate
      incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms
      and genomic moderators of BrainHQ effect. METHODS: A sample of 264 heart failure
      patients within 4 equal-sized blocks (normal/low baseline cognitive function and
      gender) will be randomly assigned to (1) BrainHQ, (2) active control computer
      based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week,
      40-hour program individualized to each patient's performance. Data collection
      will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive
      statistics, mixed model analyses, and cost-utility analysis using intent-to-treat
      approach will be computed. CONCLUSIONS: This research will provide new knowledge
      about the efficacy of BrainHQ to improve memory and increase serum brain-derived
      neurotrophic factor levels in heart failure. If efficacious, the intervention
      will provide a new therapeutic approach that is easy to disseminate to treat a
      serious comorbid condition of heart failure.

PMID- 29601370
TI  - Associations of Vitamin D Intake and Sleep Quality With Cognitive Dysfunction in
      Older Adults With Heart Failure.
AB  - BACKGROUND: Low vitamin D intake and poor sleep quality are independently
      associated with cognitive dysfunction in healthy older adults. However, the
      relationships among vitamin D intake, sleep quality, and cognitive dysfunction
      are unknown in older adults with heart failure (HF). PURPOSE: The aim of this
      study was to determine the relationships of vitamin D intake and sleep quality
      with cognitive dysfunction in older adults with HF. METHODS: A total of 160 older
      adults with HF completed the Mini-Mental State Examination to assess cognitive
      function. Vitamin D deficiency was defined as less than 15 mcg/day of average
      intake determined using a 3-day food diary and use of dietary supplements. Sleep
      quality was measured by the Pittsburgh Sleep Quality Index (PSQI). Hierarchical
      regressions and mediation analysis were used for data analysis. RESULTS: Thirty
      four patients (21.2%) had severe cognitive dysfunction (total Mini-Mental State
      Examination score <= 19), 88 (55%) had vitamin D deficiency, and 120 (75%)
      reported poor sleep quality (total PSQI score > 5). Increased daily vitamin D
      intake (beta = 0.305, P < .001) and poorer sleep quality indicated by the total
      PSQI score (beta = -0.312, P < .001) were associated with cognitive function.
      Vitamin D deficiency was associated with poor sleep quality (odds ratio, 2.22; P
      = .033). In mediation analysis, the relationship between vitamin D deficiency and
      cognitive function was mediated by sleep quality among older adults with HF.
      CONCLUSIONS: Both vitamin D deficiency and poor sleep quality are associated with
      cognitive dysfunction in older adults with HF. Interventions should be tested to
      target patients with poor sleep quality to improve cognitive function,
      particularly in those with vitamin D deficiency.

PMID- 29601371
TI  - A Survey on Sexual Counseling for Patients With Cardiac Disease Among Nurses in
      Jordan.
AB  - BACKGROUND: Recovery among patients with cardiac disease also requires attention
      to their sexual health. However, cultural, religious, and social factors may make
      Arab Muslim patients reluctant to disclose their sexual concerns and nurses
      hesitant to discuss patients' sexuality matters. OBJECTIVE: The aim of this study
      was to explore sexual counseling (SC) among nurses in Jordan in terms of
      responsibility, confidence, and practice. METHOD: This was a descriptive,
      correlational study. Staff nurses were recruited from 10 hospitals in Jordan.
      Nurses completed the cardiac version of the Survey of Sexuality-Related Nursing
      Practice and reported their demographics. RESULTS: The sample consisted of 379
      nurses (female, 59%; mean age, 28.1 years). A significant proportion of nurses
      viewed assessment/discussion of patients' sexuality matters as not within their
      responsibilities (39%), did not feel confident to address sexuality matters
      (50%), and rated themselves as not at all/not very knowledgeable about sexuality
      (60%). Few nurses were routinely integrating SC in clinical practice (9%). Sexual
      counseling was associated with nurses' gender (male, higher confidence and
      practice) and previous training on sexuality in nursing practice. CONCLUSIONS:
      Nurses in Jordan, especially female nurses, are neither prepared nor competent to
      provide SC. Nurses need focused education on sexuality to optimize patients'
      sexual health.

PMID- 29601372
TI  - Illness Uncertainty and Posttraumatic Stress in Young Adults With Congenital
      Heart Disease.
AB  - BACKGROUND: Young adults with congenital heart disease (CHD) are at risk for
      chronic illness uncertainty in 4 domains: ambiguity about the state of their
      illness; lack of information about the disease, its treatment, and comorbidities;
      complexity of the healthcare system and relationship with healthcare providers;
      and unpredictability of the illness course and outcome. Chronic uncertainty has
      been associated with posttraumatic stress symptoms (PTSS) and posttraumatic
      stress disorder (PTSD). OBJECTIVE: The aims of this study were to explore how
      young adults with CHD experience uncertainty and to describe the relationship
      between PTSS and the appraisal and management process. METHODS: An exploratory,
      mixed methods design was used. Data were collected in person and via Skype from
      25 participants (19-35 years old), who were diagnosed with CHD during childhood
      and able to read and write English. In-depth interviews and the University of
      California at Los Angeles Posttraumatic Stress Disorder Reaction Index were used
      to collect data. Qualitative data were analyzed using the constant comparative
      method. RESULTS: The 4 domains of uncertainty were evident in the narratives. The
      PTSD mean (SD) score was 31.3 (7.7). Six participants met criteria for PTSD.
      Narrative analysis revealed a relationship between severity of PTSS and the
      appraisal and management of uncertainty. Participants with PTSD used management
      strategies that included avoidance, reexperiencing, and hyperarousal.
      CONCLUSIONS: Young adults with CHD may be at risk for the development of long
      term psychological stress and PTSD in the setting of chronic uncertainty. Regular
      monitoring to identify PTSS/PTSD may be a means to promote treatment adherence
      and participation in healthcare.

PMID- 29601373
TI  - Decreased Quality of Life Due to Driving Restrictions After Cardioverter
      Defibrillator Implantation.
AB  - BACKGROUND: Driving restrictions for patients with an implantable cardioverter
      defibrillator (ICD) may require significant lifestyle adjustment and affect
      patients' psychological well-being. This study explored the prevalence of, and
      factors associated with, patient-reported decrease in quality of life due to
      driving restrictions in the first 2 months postimplantation. METHODS: Dutch ICD
      patients (N = 334; median age, 64 [interquartile range, 55-70) years; 81% male)
      completed questionnaires at the time of implantation and 4 months
      postimplantation, assessing their sociodemographic, psychological, and driving
      related characteristics. Clinical baseline data were retrieved from patients'
      medical records. RESULTS: Nearly half of the patients (49%) reported decreased
      quality of life due to driving restrictions. Patient-reported reasons included
      dependency on others/public transport, (social) isolation, and inability to work.
      Patients reporting decreased quality of life were more likely to be younger (P =
      .01), to feel that the restriction lasts too long (P = .004), to have considered
      ICD refusal because of the restrictions (P = .03), and to have Type D personality
      (P = .02), anxiety (P = .05), depression (P = .003), and ICD-related concerns (P
      = .02). Multivariable analysis showed that being younger than 60 years (odds
      ratio [OR], 2.30; 95% confidence interval [CI], 1.09-4.88; P = .03), feeling the
      driving restriction lasts too long (OR, 1.77; 95% CI, 1.23-2.55; P = .002), and
      depression (OR, 3.21; 95% CI, 1.09-9.47; P = .035) were independently associated
      with decreased quality of life due to driving restrictions. CONCLUSIONS: This
      study indicated that a significant group of ICD patients may experience decreased
      quality of life because of the driving restrictions postimplantation. The
      restrictions seem to particularly affect patients who are younger and distressed
      and patients who feel that the restriction lasts too long.

PMID- 29601375
TI  - Cultural Tailoring of Health Information and the Potential of the Internet.

PMID- 29601374
TI  - User-centered Development of a Decision Aid for Patients Facing Implantable
      Cardioverter-Defibrillator Replacement: A Mixed-Methods Study.
AB  - BACKGROUND: Because of battery depletion, an implantable cardioverter
      defibrillator (ICD) generator requires surgical replacement every 5 to 7 years.
      Routine replacement is the norm without discussion with patients about whether or
      not to proceed. OBJECTIVE: The aim of this study was to develop a patient
      decision aid (PDA) for patients facing ICD replacement and plan for its
      implementation. METHODS: An embedded mixed-methods study was conducted using
      questionnaires and semistructured interviews focused on current ICD replacement
      practices; PDA acceptability, usability, and content; and PDA implementation.
      Transcripts were analyzed using constant comparative analysis. RESULTS: Eighteen
      PDA end users in 16 interviews characterized the current ICD replacement approach
      as automatic without consideration for patient preferences. The PDA was
      positively received, and the content was iteratively revised 4 times during the
      interviews. Changes were related to missing and excess information, language, and
      wording. The PDA was identified as a means to support a shared decision-making
      (SDM) process, not to be used as a standalone instrument. To shift current
      practices to an SDM process, participants identified that an invitation to
      discuss the option of ICD replacement is required-whether initiated by the
      patient or the clinician. CONCLUSION: Currently, the option of ICD replacement is
      rarely offered, and patient preferences are seldom elicited. Participants
      believed the PDA to be a useful intervention that could help facilitate an SDM
      process for patients facing ICD replacement. Preparing for implementation during
      the development phase will allow us to strategize effectively to overcome
      perceived barriers and capitalize on perceived facilitators during actual
      implementation.

PMID- 29601376
TI  - The Influence of beta-Adrenergic Receptor Kinase-1 on Stroke-induced
      Immunodeficiency Syndrome.
AB  - BACKGROUND: Immunodeficiency in acute ischemic stroke (AIS) is thought to be a
      result of norepinephrine suppression of the lymphoid tissue. The possible
      differences in the distribution of lymphocytes after stroke may be due to
      differences in responsiveness of lymphocyte beta-adrenergic receptors to their
      kinase (BARK-1). OBJECTIVE: The objective was to quantify the influence of
      lymphocyte BARK-1 on stroke-induced immunodeficiency in AIS patients. METHODS: A
      prospective clinical cohort study was conducted (N = 44). Measures included age,
      gender, race, risk factors for stroke, stroke severity, comorbidities, presence
      of infection, white blood cell counts and differential proportions, and
      lymphocyte BARK-1. Student t tests, effect sizes, and linear and logistic
      regressions were conducted to test the study objective. The study was approved by
      the Oregon Health & Science University Institutional Review Board. RESULTS: There
      were significant changes in all white blood cells and differential proportions
      and in the National Institutes of Health Stroke Scale from admission to 48 hours
      after onset of stroke deficits. Higher BARK-1 influenced the lower lymphocyte
      proportion at 48 hours, independent of age, P < .0001. Furthermore, BARK-1 also
      was associated with an increase in the likelihood of having sustained or stroke
      induced immunodeficiency at 48 hours: odds ratio, 2.41; 95% confidence interval,
      1.10-5.25; P = .027, and odds ratio, 2.79; 95% confidence interval, 1.03-7.52; P
      = .043, respectively. In all backward stepwise selection of factors, BARK-1 was
      the only factor consistently retained in the models. CONCLUSIONS: beta-Adrenergic
      receptor kinase-1 has a significant quantifiable influence on lymphocyte
      proportion at 48 hours and on the classification of sustained stroke-induced
      immunodeficiency. CLINICAL IMPLICATIONS: beta-Adrenergic stimulation influences
      immunodeficiency in AIS.

PMID- 29601377
TI  - Seasonal Work and Cardiovascular Risk Factors in Farmers.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death and
      hospitalization in the rural United States. Midwestern farmers are integral to
      rural communities, but little is known about the effect of occupational
      variability of seasonal work and technology use on their cardiovascular disease
      risk. AIMS: This study describes the relationships of health behaviors and
      cardiovascular disease risk in 40 Midwestern farmers during peak and off-peak
      farming seasons. METHODS: Objectively measured physical activity and self-report
      of demographics, diet, and health-related quality of life were collected during
      each farming season. RESULTS AND CONCLUSIONS: Farmers in this study were
      physically active, ate consistent diets, and reported high health status ratings
      throughout the year. Cardiovascular disease risk was positively correlated with
      age and body mass index (P < .01), and half of young and middle-age farmers
      reported anxiety and depression problems. Cardiovascular disease risk reduction
      interventions for farmers should address both physical and emotional aspects of
      farming.

PMID- 29601378
TI  - Is Anesthesia Technique Associated With a Higher Risk of Mortality or
      Complications Within 90 Days of Surgery for Geriatric Patients With Hip
      Fractures?
AB  - BACKGROUND: Postoperative mortality and complications after geriatric hip
      fracture surgery remain high despite efforts to improve perioperative care for
      these patients. One factor of particular interest is anesthetic technique, but
      prior studies on this are limited by sample selection, competing risks, and
      incomplete followup. QUESTIONS/PURPOSES: (1) Among older patients undergoing
      surgery for hip fracture, does 90-day mortality differ depending on the type of
      anesthesia received? (2) Do 90-day emergency department returns and hospital
      readmissions differ based on anesthetic technique after geriatric hip fracture
      repairs? (3) Do 90-day Agency for Healthcare Research and Quality (AHRQ) outcomes
      differ according to anesthetic techniques used during hip fracture surgery?
      METHODS: We conducted a retrospective study on geriatric patients (65 years or
      older) with hip fractures between 2009 and 2014 using the Kaiser Permanente Hip
      Fracture Registry. A total of 1995 (11%) of the surgically treated patients with
      hip fracture were excluded as a result of missing anesthesia information. The
      final study sample consisted of 16,695 patients. Of these, 2027 (12%) died and 98
      (< 1%) terminated membership during followup, which were handled as competing
      events and censoring events, respectively. Ninety-day mortality, emergency
      department returns, hospital readmission, deep vein thrombosis (DVT) or pulmonary
      embolism (PE), myocardial infarction (MI), and pneumonia were evaluated using
      multivariable competing risk proportional subdistribution hazard regression
      according to type of anesthesia technique: general anesthesia, regional
      anesthesia, or conversion from regional to general. Of the 16,695 patients, 58%
      (N = 9629) received general anesthesia, 40% (N = 6597) received regional
      anesthesia, and 2.8% (N = 469) patients were converted from regional to general.
      RESULTS: Compared with regional anesthesia, patients treated with general
      anesthesia had a higher likelihood of overall 90-day mortality (hazard ratio
      [HR], 1.22; 95% confidence interval [CI], 1.11-1.35; p < 0.001); however, when
      stratified by before and after hospital discharge but within 90 days of surgery,
      this higher risk was only observed during the inpatient stay (HR, 3.83; 95% CI,
      3.18-4.61; p < 0.001); no difference was observed after hospital discharge (HR,
      1.04; 95% CI, 0.94-1.16; p = 0.408). Patients undergoing conversion from regional
      to general also had a higher overall mortality risk compared with those
      undergoing regional anesthesia (HR, 1.34; 95% CI 1.04-1.74; p = 0.026), but this
      risk was only observed during their inpatient stay (HR, 6.84; 95% CI, 4.21-11.11;
      p < 0.001) when stratifying by before and after hospital discharge. Patients
      undergoing general anesthesia had a higher risk for all-cause readmission when
      compared with regional anesthesia (HR, 1.09; 95% CI, 1.01-1.19; p = 0.026). No
      differences according to anesthesia type were observed for risk of 90-day AHRQ
      outcomes, including DVT/PE, MI, and pneumonia. CONCLUSIONS: We found the use of
      general anesthesia and conversion from regional to general anesthesia were
      associated with a higher risk of mortality during the in-hospital stay compared
      with regional anesthetic techniques, but this higher risk did not persist after
      hospital discharge. We also found general anesthesia to be associated with a
      higher risk of all-cause readmission compared with regional, but no other
      differences were observed in risk for complications. Our findings suggest
      regional anesthetic techniques may be preferred when possible in this patient
      population. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 29601379
TI  - Moderate to Severe Renal Insufficiency Is Associated With High Mortality After
      Hip and Knee Replacement.
AB  - BACKGROUND: In patients having elective hip or knee replacements, many comorbid
      conditions, including diabetes, cardiovascular disease, and congestive heart
      failure, are associated with postoperative mortality. Renal failure and a history
      of renal transplantation also increase mortality. However, the effect of
      different stages of chronic kidney disease on patients' prognoses is unclear.
      QUESTIONS/PURPOSES: (1) What is the risk of postoperative mortality in different
      stages of chronic kidney disease after elective hip or knee replacement and does
      the risk increase with mild renal insufficiency? (2) How severe is the risk of
      death in patients with chronic kidney disease compared with other major medical
      comorbidities such as diabetes, cardiovascular disease, and congestive heart
      failure? (3) Are there risk factor combinations associated with especially poor
      survival? METHODS: Using longitudinally maintained databases, the records of
      18,575 patients (median age 69 years, 63% female, median body mass index 29 kg/m)
      undergoing elective hip and knee replacements from a single center between 2002
      and 2011 were analyzed in this retrospective study. A total of 6519 (35%)
      patients had Stage I, 9917 (53%) Stage II, 2023 (11%) Stage III, 81 (0.4%) Stage
      IV, and 35 (0.2%) Stage V chronic kidney disease. Kaplan-Meier analysis was used
      to analyze mortality at different stages of the disease. Cox regression analysis
      was performed to compare the risk of death associated with the comorbid
      conditions of interest. Comorbid conditions with greatest risk for death
      (diabetes, coronary artery disease, and congestive heart failure) were combined
      separately with chronic kidney disease using logistic regression. According to
      data from the Finnish Population Register Centre, a total of 4055 deaths occurred
      in our patient cohort during the followup period. The median followup was 7.8
      years (range, 0-14 years; interquartile range, 5.8-10.0 years). RESULTS: The mean
      survival time was 13 years (95% confidence interval [CI], 12.5-12.7 years) in
      Stage I, 11 years (95% CI, 11.3-11.5 years) in Stage II, 9 years (95% CI, 9.2-9.7
      years) in Stage III, 7 years (95% CI, 5.6-7.5 years) in Stage IV, and 6 years
      (95% CI, 4.9-8.0 years) in Stage V (p < 0.001). Compared with Stage I chronic
      kidney disease, the risk of death increased with every step of the disease
      (adjusted hazard ratio [HR], 1.9 [95% CI, 1.76-2.10]; HR, 3.8 [95% CI, 3.39
      4.19]; and HR, 8.1 [95% CI, 6.33-10.31] in Stages II, III, and IV-V,
      respectively). Compared with congestive heart failure (HR, 2.11 [95% CI, 1.81
      2.45], p < 0.001), coronary disease (HR, 1.54 [95% CI, 1.40-1.69], p < 0.001),
      diabetes (HR, 1.71 [95% CI, 1.54-1.90], p < 0.001), and hypertension (HR, 1.35
      [95% CI, 1.26-1.45], p < 0.001), Stage III and Stage IV to V chronic kidney
      disease are associated with poorer survival. The combination of chronic kidney
      disease and diabetes (odds ratio [OR], 8.15 [95% CI, 4.9-13.51]) had a
      synergistic effect on the risk of death compared with chronic kidney disease (OR,
      2.36 [95% CI, 1.70-3.28]) or diabetes alone (OR, 1.19 [95% CI, 0.70-2.03]) during
      the first postoperative year. CONCLUSIONS: All stages of chronic kidney disease
      have a harmful effect on long-term life expectancy in joint replacement
      recipients. The risk becomes clinically meaningful in the most severe forms of
      the disease, but also in moderate chronic kidney disease when it is accompanied
      by diabetes, coronary disease, or congestive heart failure. It should be
      recognized that these patients achieve fewer quality-adjusted life-years even if
      clinical outcomes were similar. The effect of chronic kidney disease on cost
      effectiveness of hip and knee replacements should be investigated in future
      studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 29601380
TI  - Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve
      Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study.
AB  - BACKGROUND: The suture-tendon interface is often the weakest link in tendon-to
      tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent
      derived from the gardenia fruit that can enhance suture force to failure of the
      tendon-suture interface. Viable methods for intraoperative clinical delivery of
      genipin could be of clinical utility, but to our knowledge have not yet been
      extensively studied. QUESTIONS/PURPOSES: The purposes of this study were (1) to
      evaluate whether sutures precoated with genipin can augment the suture-tendon
      interface to improve force to failure, stiffness, and work to failure in healthy
      and degenerated tendons; and (2) to determine the effect of genipin on the extent
      and distribution of crosslinking. METHODS: Single-stitch suture pullout tests
      were performed ex vivo on 25 bovine superficial digital flexor tendons. To assess
      effects on native tissue, one group of 12 tendons was cut in proximal and distal
      halves and randomized to treatment (n = 12) and control groups (n = 12) in a
      matched-pair design. One simple stitch with a loop with either a normal suture or
      genipin-coated suture was applied to tendons in both groups. To simulate a
      degenerative tendon condition, a second group of 13 tendons was cut in proximal
      and distal halves, injected with 0.2 mL of collagenase D (8 mg/mL) and incubated
      for 24 hours before suturing with either a genipin-coated suture (n = 13) or
      their matched controls (n = 13). Sutures from all groups then were loaded to
      failure on a universal materials testing machine 24 hours after suturing. Suture
      pullout force, stiffness, and work to failure were calculated from force
      displacement data and compared between the groups. Additionally, fluorescence was
      measured to determine the degree of crosslinking quantitatively and a qualitative
      analysis of the distribution pattern was performed by microscopy. RESULTS: In
      healthy tendon pairs, the median maximum pullout force was greater with genipin
      coated sutures than with control sutures (median, 42 N [range, 24-73 N] versus 29
      N [range, 13-48 N]; difference of medians, 13 N; p = 0.003) with corresponding
      increases in the required work to failure (median, 275 mJ [range, 48-369 mJ]
      versus 148 mJ [range, 83-369 mJ]; difference of medians, 127 mJ; p = 0.025) but
      not stiffness (median, 4.1 N/mm [range, 2.3-8.1 N/mm] versus 3.3 N/mm [range, 1.1
      9.6 N/mm]; difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons,
      median maximum pullout force was greater with genipin-coated sutures than with
      control sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N];
      difference of medians, 3 N; p = 0.034) with no differences in work to failure
      (median, 75 mJ [range, 11-249 mJ] versus 53 mJ [range, 14-143 mJ]; difference of
      medians, 22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7-13.4 N/mm]
      versus 1.6 N/mm [range, 0.5-5.6 N/mm]; difference of medians, 0.3 N/mm; p =
      0.285). Fluorescence was higher in tendons treated with genipin-coated sutures
      compared with the control group, whereas higher fluorescence was observed in the
      treated healthy compared with the degenerated tendons (difference of means -3.16;
      standard error 1.08; 95% confidence interval [CI], 0.97-5.34; p = 0.006/healthy
      genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p <
      0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p < 0.001).
      CONCLUSIONS: Genipin-coated sutures improved force to failure of a simple stitch
      at the tendon-suture interface in healthy and degenerated tendons in an ex vivo
      animal model. Fluorescence was higher in tendons treated with genipin-coated
      sutures compared with the control group. CLINICAL RELEVANCE: A genipin-coated
      suture represents a potential delivery vehicle for exogenous crosslink agents to
      augment suture retention properties. In vivo animal studies are the next logical
      step to assess safety and efficacy of the approach.

PMID- 29601381
TI  - Does the Alpha-defensin Immunoassay or the Lateral Flow Test Have Better
      Diagnostic Value for Periprosthetic Joint Infection? A Systematic Review.
AB  - BACKGROUND: Measuring alpha-defensin concentrations in synovial fluid may help to
      diagnose periprosthetic joint infection (PJI). There are two commercially
      available methods for measuring alpha-defensin in synovial fluid: the enzyme
      linked immunosorbent assay-based Synovasure(r) alpha-defensin immunoassay, which
      gives a numeric readout within 24 hours, and the Synovasure lateral flow test,
      which gives a binary readout within 20 minutes. There is no compilation of the
      existing literature to support the use of one of these two tests over the other.
      QUESTIONS/PURPOSES: Does the immunoassay or the lateral flow test have better
      diagnostic value (sensitivity and specificity) in diagnosing PJI? METHODS: We
      followed PRISMA guidelines and identified all studies on alpha-defensin
      concentration in synovial fluid as a PJI diagnostic marker, indexed to April 14,
      2017, in PubMed, JSTOR, Google Scholar, and OVID databases. The search retrieved
      1578 records. All prospective and retrospective studies on alpha-defensin as a
      PJI marker (PJI classified according to the criteria of the Musculoskeletal
      Infection Society) after THA or TKA were included in the analysis. All studies
      used only one of the two commercially available test methods, but none of them
      was comparative. After excluding studies with overlapping patient populations,
      four studies investigating the alpha-defensin immunoassay and three investigating
      the lateral flow test remained. Alpha-defensin immunoassay studies included 482
      joints and lateral flow test studies included 119. The quality of the trials was
      assessed according to the Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS-2) tool. The heterogeneity among studies was evaluated by the I index,
      indicating that the heterogeneity of the included studies was low. Pooled
      sensitivity, specificity, positive and negative likelihood ratios, and receiver
      operating curves were calculated for each method and compared with each other.
      RESULTS: The alpha-defensin immunoassay had superior overall diagnostic value
      compared with the lateral flow test (area under the curve, 0.98 versus 0.75) with
      higher sensitivity (96% [90%-98%] versus 71% [55%-83%], p < 0.001), but no
      difference in specificity with the numbers available (96% [93%-97%] versus 90%
      [81%-95%], p = 0.060). CONCLUSIONS: Measurement of alpha-defensin in synovial
      fluid is a valuable complement to existing diagnostic criteria, and the
      immunoassay test detects PJI more accurately than the lateral flow test. The
      lateral flow test has lower sensitivity, making it difficult to rule out
      infection, but its relatively high specificity combined with the advantage of a
      quick response time can make it useful to rule in infection perioperatively.
      LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 29601382
TI  - Classification in Brief: SRS-Schwab Classification of Adult Spinal Deformity.

PMID- 29601383
TI  - Is Platelet-rich Plasma Injection Effective for Chronic Achilles Tendinopathy? A
      Meta-analysis.
AB  - BACKGROUND: Chronic Achilles tendinopathy is common in the general population,
      and platelet-rich plasma (PRP) is seeing increased use to treat this problem.
      However, studies disagree as to whether PRP confers a beneficial effect for
      chronic Achilles tendinopathy, and no one to our knowledge has pooled the
      available randomized trials in a formal meta-analysis to try to reconcile those
      differences. QUESTIONS/PURPOSES: In the setting of a systematic review and meta
      analysis of randomized controlled trials (RCTs), we asked: Does PRP plus
      eccentric strength training result in (1) greater improvements in Victorian
      Institute of Sports Assessment-Achilles (VISA-A) scores; (2) differences in
      tendon thickness; or (3) differences in color Doppler activity compared with
      placebo (saline) injections plus eccentric strength training in patients with
      chronic Achilles tendinopathy? METHODS: A search of peer-reviewed articles was
      conducted to identify all RCTs using PRP injection with eccentric training for
      chronic Achilles tendinopathy in the electronic databases of PubMed, Web of
      Science (SCI-E/SSCI/A&HCI), and EMBASE from January 1981 to August 2017. Results
      were limited to human RCTs and published in all languages. Two reviewers assessed
      study quality using the Cochrane Collaboration risk-of-bias tool. All the
      included studies had low risk of bias. The primary endpoint was improvement in
      the VISA-A score, which ranges from 0 to 100 points, with higher scores
      representing increased activity and less pain; we considered the minimum
      clinically important difference on the VISA-A to be 12 points. Secondary outcomes
      were tendon thickness change (with a thicker tendon representing more severe
      disease), color Doppler activity (with more activity representing a poorer
      result), and other functional measures (such as pain and return to sports
      activity). Four RCTs involving 170 participants were eligible and included 85
      participants treated with PRP injection and eccentric training and 85 treated
      with saline injection and eccentric training. The patients in both PRP and
      placebo (saline) groups seemed comparable at baseline. We assessed for
      publication bias using a funnel plot and saw no evidence of publication bias.
      Based on previous studies, we had 80% power to detect a 12-point difference on
      the VISA-A score with the available sample size in each group. RESULTS: With the
      numbers available, there was no difference between the PRP and saline groups
      regarding the primary outcome (VISA-A score: mean difference [MD], 5.3; 95%
      confidence interval [CI], -0.7 to 11.3; p = 0.085). Likewise, we found no
      difference between the PRP and saline groups in terms of our secondary outcomes
      of tendon thickness change (MD, 0.2 mm; 95% CI, 0.6-1.0 mm; p = 0.663) and color
      Doppler activity (MD, 0.1; 95% CI, -0.7 to 0.4; p = 0.695). CONCLUSIONS: PRP
      injection with eccentric training did not improve VISA-A scores, reduce tendon
      thickness, or reduce color Doppler activity in patients with chronic Achilles
      tendinopathy compared with saline injection. Larger randomized trials are needed
      to confirm these results, but until or unless a clear benefit has been
      demonstrated in favor of the new treatment, we cannot recommend it for general
      use. LEVEL OF EVIDENCE: Level I, therapeutic study.

PMID- 29601384
TI  - Are Age and Patient Gender Associated With Different Rates and Magnitudes of
      Clinical Improvement After Reverse Shoulder Arthroplasty?
AB  - BACKGROUND: An improved understanding of how gender differences and the natural
      aging process are associated with differences in clinical improvement in outcome
      metric scores and ROM measurements after reverse total shoulder arthroplasty
      (rTSA) may help physicians establish more accurate patient expectations for
      reducing postoperative pain and improving function. QUESTIONS/PURPOSES: (1) Is
      gender associated with differences in rTSA outcome scores like the Simple
      Shoulder Test (SST), the UCLA Shoulder score, the American Shoulder and Elbow
      Surgeons (ASES) Shoulder score, the Constant Shoulder score, and the Shoulder
      Pain and Disability Index (SPADI) and ROM? (2) Is age associated with differences
      in rTSA outcome scores and ROM? (3) What factors are associated with the combined
      interaction effect between age and gender? (4) At what time point during recovery
      does most clinical improvement occur, and when is full improvement reached?
      METHODS: We quantified and analyzed the outcomes of 660 patients (424 women and
      236 men; average age, 72 +/- 8 years; range, 43-95 years) with cuff tear
      arthropathy or osteoarthritis and rotator cuff tear who were treated with rTSA by
      13 shoulder surgeons from a longitudinally maintained international database
      using a linear mixed effects statistical model to evaluate the relationship
      between clinical improvements and gender and patient age. We used five outcome
      scoring metrics and four ROM assessments to evaluate clinical outcome
      differences. RESULTS: When controlling for age, men had better SST scores (mean
      difference [MD] = 1.41 points [95% confidence interval {CI}, 1.07-1.75], p <
      0.001), UCLA scores (MD = 1.76 [95% CI, 1.05-2.47], p < 0.001), Constant scores
      (MD = 6.70 [95% CI, 4.80-8.59], p < 0.001), ASES scores (MD = 7.58 [95% CI, 5.27
      9.89], p < 0.001), SPADI scores (MD = -12.78 [95% CI, -16.28 to -9.28], p <
      0.001), abduction (MD = 5.79 degrees  [95% CI, 2.74-8.84], p < 0.001), forward
      flexion (MD = 7.68 degrees  [95% CI, 4.15-11.20], p < 0.001), and passive
      external rotation (MD = 2.81 degrees  [95% CI, 0.81-4.8], p = 0.006). When
      controlling for gender, each 1-year increase in age was associated with an
      improved ASES score by 0.19 points (95% CI, 0.04-0.34, p = 0.011) and an improved
      SPADI score by -0.29 points (95% CI, -0.46 to 0.07, p = 0.020). However, each 1
      year increase in age was associated with a mean decrease in active abduction by
      0.26 degrees  (95% CI, -0.46 to 0.07, p = 0.007) and a mean decrease of forward
      flexion by 0.39 degrees  (95% CI, -0.61 to 0.16, p = 0.001). A combined
      interaction effect between age and gender was found only with active external
      rotation: in men, younger age was associated with less active external rotation
      and older age was associated with more active external rotation (beta0
      [intercept] = 11.029, beta1 [slope for age variable] = 0.281, p = 0.009).
      Conversely, women achieved no difference in active external rotation after rTSA,
      regardless of age at the time of surgery (beta0 [intercept] = 34.135, beta1
      [slope for age variable] = -0.069, p = 0.009). Finally, 80% of patients achieved
      full clinical improvement as defined by a plateau in their outcome metric score
      and 70% of patients achieved full clinical improvement as defined by a plateau in
      their ROM measurements by 12 months followup regardless of gender or patient age
      at the time of surgery with most improvement occurring in the first 6 months
      after rTSA. CONCLUSIONS: Gender and patient age at the time of surgery were
      associated with some differences in rTSA outcomes. Men had better outcome scores
      than did women, and older patients had better outcome scores but smaller
      improvements in function than did younger patients. These results demonstrate
      rTSA outcomes differ for men and women and for different patient ages at the time
      of surgery, knowledge of these differences, and also the timing of improvement
      plateaus in outcome metric scores and ROM measurements can both improve the
      effectiveness of patient counseling and better establish accurate patient
      expectations after rTSA. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 29601386
TI  - CORR Insights(r): Is Anesthesia Technique Associated With a Higher Risk of
      Mortality or Complications Within 90 Days of Surgery for Geriatric Patients With
      Hip Fractures?

PMID- 29601387
TI  - CORR Insights(r): What Factors Are Associated With Implant Breakage and Revision
      After Intramedullary Nailing for Femoral Metastases?

PMID- 29601385
TI  - Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and
      Is Not a Spontaneous Model of Metastasis: A Mouse Osteosarcoma Model.
AB  - BACKGROUND: Although metastasis is the major cause of mortality in patients with
      osteosarcoma, little is known about how micrometastases progress to gross
      metastatic disease. Clinically relevant animal models are necessary to facilitate
      development of new therapies to target indolent pulmonary metastases. Intratibial
      injection of human and murine osteosarcoma cell lines have been described as
      orthotopic models that develop spontaneous pulmonary metastasis over time.
      However, there is variability in reported injection techniques and metastatic
      efficiency. QUESTIONS/PURPOSES: We aimed to characterize a widely used murine
      model of metastatic osteosarcoma, determine whether it is appropriate to study
      spontaneous pulmonary metastasis by establishing a reliable volume for
      intratibial injection, determine the incidence of primary tumor and metastatic
      formation, determine the kinetics of pulmonary metastatic seeding and outgrowth,
      and the contribution of the primary tumor to subsequent development of
      metastasis. METHODS: The metastatic mouse osteosarcoma cell line K7M2 was
      injected into the tibia of mice. The maximum volume that could be injected
      without leakage was determined using Evan's blue dye (n = 8 mice). Primary tumor
      formation and metastatic efficiency were determined by measuring the incidence of
      primary tumor and metastatic formation 4 weeks after intratibial injection (n =
      30). The kinetics of metastatic development were determined by performing serial
      euthanasia at 1, 2, 3, and 4 weeks after injection (n = 24; five to six mice per
      group). Number of metastatic foci/histologic lung section and metastatic
      burden/lung section (average surface area of metastatic lesions divided by the
      total surface area of the lung) was calculated in a blinded fashion. To test the
      contribution of the primary tumor to subsequent metastases, amputations were
      performed 30 minutes, 4 hours, or 24 hours after injection (n = 21; five to six
      mice per group). Mice were euthanized after 4 weeks and metastatic burden
      calculated as described previously, comparing mice that had undergone amputation
      with control, nonamputated mice. Differences between groups were calculated using
      Kruskal-Wallis and one-way analysis of variance. RESULTS: The maximum volume of
      cell suspension that could be injected without leakage was 10 MUL. Intratibial
      injection of tumor cells led to intramedullary tumor formation in 93% of mice by
      4 weeks and resulted in detectable pulmonary metastases in 100% of these mice as
      early as 1 week post-injection. Metastatic burden increased over time (0.88% +/-
      0.58, week 1; 6.6% +/- 5.3, week 2; 16.1% +/- 12.5, week 3; and 40.3% +/- 14.83,
      week 4) with a mean difference from week 1 to week 4 of -39.38 (p < 0.001; 95%
      confidence interval [CI], -57.39 to -21.37), showing pulmonary metastatic growth
      over time. In contrast, the mean number of metastatic foci did not increase from
      week 1 to week 4 (36.4 +/- 33.6 versus 49.3 +/- 26.3, p = 0.18). Amputation of
      the injected limb at 30 minutes, 4 hours, and 24 hours after injection did not
      affect pulmonary metastatic burden at 4 weeks, with amputation as early as 30
      minutes post-injection resulting in a metastatic burden equivalent to tumor
      bearing controls (48.9% +/- 6.1% versus 40.9% +/- 15.3%, mean difference 7.96, p
      = 0.819; 95% CI, -33.9 to 18.0). CONCLUSIONS: There is immediate seeding of the
      metastatic site after intratibial injection of the K7M2 osteosarcoma cell line,
      independent of a primary tumor. This is therefore not a model of spontaneous
      metastasis. CLINICAL RELEVANCE: This model should not be used to study the early
      components of the metastatic cascade, but rather used as an experimental model of
      metastasis. Improved understanding of this commonly used model will allow for
      proper interpretation of existing data and inform the design of future studies
      exploring the biology of metastasis in osteosarcoma.

PMID- 29601388
TI  - Art in Science: Jusepe de Ribera's Puzzle in The Clubfoot.

PMID- 29601389
TI  - Letter to the Editor: Stem Cells Combined With Platelet-rich Plasma Effectively
      Treat Corticosteroid-induced Osteonecrosis of the Hip: A Prospective Study.

PMID- 29601390
TI  - CORR Insights(r): Bearing Dislocation and Progression of Osteoarthritis After
      Mobile-bearing Unicompartmental Knee Arthroplasty Vary Between Asian and Western
      Patients: A Meta-analysis.

PMID- 29601391
TI  - CORR Insights(r): What Is the Long-term Survival for Primary THA With Small-head
      Metal-on-metal Bearings?

PMID- 29601392
TI  - Your Best Life: Resiliency and the Art of Medicine.

PMID- 29601393
TI  - CORR Insights(r): Increased Radiation but No Benefits in Pedicle Screw Accuracy
      With Navigation versus a Freehand Technique in Scoliosis Surgery.

PMID- 29601394
TI  - CORR Insights(r): Etiology of Above-knee Amputations in the United States: Is
      Periprosthetic Joint Infection an Emerging Cause?

PMID- 29601395
TI  - CORR Insights(r): Is NS-EDTA Effective in Clearing Bacteria From Infected Wounds
      in a Rat Model?

PMID- 29601396
TI  - CORR Insights(r): Does the Alpha-defensin Immunoassay or the Lateral Flow Test
      Have Better Diagnostic Value for Periprosthetic Joint Infection? A Systematic
      Review.

PMID- 29601397
TI  - CORR Insights(r): Can Patient Selection Explain the Obesity Paradox in
      Orthopaedic Hip Surgery? An Analysis of the ACS-NSQIP Registry.

PMID- 29601398
TI  - CORR Insights(r): Moderate to Severe Renal Insufficiency Is Associated With High
      Mortality After Hip and Knee Replacement.

PMID- 29601399
TI  - Reply to the Letter to the Editor: Stem Cells Combined With Platelet-rich Plasma
      Effectively Treat Corticosteroid-induced Osteonecrosis of the Hip: A Prospective
      Study.

PMID- 29601400
TI  - Cochrane in CORR(r): Interventions for the Reduction of Prescribed Opioid Use in
      Chronic Non-cancer Pain.

PMID- 29601401
TI  - Should Emergency Department Attendances be Used With or Instead of Readmission
      Rates as a Performance Metric?: Comparison of Statistical Properties Using
      National Data.
AB  - BACKGROUND: Hospital readmissions are common and are viewed as unfavorable. They
      are commonly used as a measure of quality of care and, in the United States and
      England, are associated with financial penalties. Readmissions are not the only
      possible return-to-acute-care metric; patients may also attend emergency
      departments (ED). OBJECTIVE: To assess hospital-level return-to-acute-care
      metrics using statistical criteria. RESEARCH DESIGN: Patient readmissions and/or
      ED attendances were aggregated to produce risk-standardized hospital rates.
      Return-to-acute-care rates at 7, 30, 90, and 365 days were assessed using key
      statistical properties: (i) variability between hospitals; (ii) the relative
      contribution of patient and nonpatient factors to variation; and (iii) the
      statistical power to detect performance differences. SUBJECTS: We had
      pseudonymized administrative data on all inpatient hospital admissions and ED
      attendances in National Health Service hospitals in England between April 2009
      and March 2011. Patients with an inpatient stay for chronic obstructive pulmonary
      disorder or heart failure were eligible for inclusion. MEASURES: ED attendances
      and readmissions for patients discharged from an inpatient stay for chronic
      obstructive pulmonary disorder or heart failure. RESULTS: Interhospital variation
      was greatest for ED attendance; in addition, readmission was more strongly
      determined by patient characteristics than was ED attendance or both combined.
      Because of smaller numbers, the statistical power to detect differences in rates
      at 7 days for any indicator was limited. CONCLUSIONS: Despite the current
      emphasis on readmissions, we found that ED attendance within 30 days has more
      desirable statistical properties and therefore the potential to be a useful
      metric when comparing hospitals.

PMID- 29601402
TI  - Risk Factors for Anal Dysplasia in Transgender Women: A Retrospective Chart
      Review.
AB  - OBJECTIVE: The aim of the study was to assess risk factors for anal human
      papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender
      women (TGW). METHODS: A retrospective chart review was conducted based on
      electronic medical records of TGW patients seen in the University of Miami Health
      System between 2010 and 2016. Outcome measures included risk factors of anal
      dysplasia, including HIV infection, receptive anal intercourse, and smoking
      history. Descriptive statistical analysis and chi testing were used. RESULTS:
      Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to
      72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were
      black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV
      positive, and 28 (72%) among those with known partner preference (n = 39)
      reported male partners. Male partner preference was significantly associated with
      being black/African descent (p = .009) and being single (p = .048). Older age was
      significantly associated with HIV-positive status (p = .023). The average number
      of risk factors per person was 2.10 (0.97). Sixty-one years or older had the
      highest average number of risk factors (2.90 [0.88]). CONCLUSIONS: Because rates
      of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia
      continue to persist among TGW, this study reinforces the need to increase the
      focus on anal health in the care of TGW and the need for further research to
      guide patient care and anal dysplasia screening strategies among those
      individuals.

PMID- 29601403
TI  - Brief Report: Differential Timing of Cholesterol Increase During Successful HCV
      Therapy: Impact of Type of Drug Combination.
AB  - OBJECTIVE: To evaluate factors associated with increased serum cholesterol levels
      during interferon-free hepatitis C virus (HCV) therapy. DESIGN: Prospective
      longitudinal study. METHODS: HIV-infected patients who started and successfully
      completed interferon-free therapy for chronic HCV infection were included.
      Patients were treated using 2 different regimens, based on the clinician's
      opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with
      ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density
      lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of
      treatment (EOT), weeks SVR4, SVR12, and SVR24. RESULTS: The study population
      therefore comprised 85 patients reaching sustained virological response, 42
      (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients
      using SOF/LDV was showed a higher increase on both total cholesterol and low
      density lipoprotein cholesterol during treatment period than those receiving
      PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT,
      choice of HCV regimen was associated with differential increases in total
      cholesterol during therapy. After EOT, no differences were found between SOF/LDV
      and PrOD with respect to total cholesterol. CONCLUSIONS: Our study suggests that
      the differential timing of the restoration of cholesterol metabolism in HIV/HCV
      genotype 1 coinfected patients achieving sustained virological response is not
      mediated by HCV clearance but depends on the drug combination used.

PMID- 29601404
TI  - Financial Incentives to Motivate Pediatric HIV Testing-Assessing the Potential
      for Coercion, Inducement, and Voluntariness.

PMID- 29601405
TI  - High-Risk Prescription Opioid Use Among People Living With HIV.
AB  - BACKGROUND: Prescription opioid use is greater among people living with HIV
      (PLWH), yet little is known about the prevalence of specific types of high-risk
      use among these individuals. SETTING: We analyzed clinical and demographic data
      from the HIV Research Network and prescribing data from Medicaid for noncancer
      patients seeking HIV treatment at 4 urban clinics between 2006 and 2010. METHODS:
      HIV Research Network patients were included in the analytic sample if they
      received at least one incident opioid prescription. We examined 4 measures of
      high-risk opioid use: (1) high daily dosage; (2) early refills; (3) overlapping
      prescriptions; and (4) multiple prescribers. RESULTS: Of 4605 eligible PLWH, 1814
      (39.4%) received at least one incident opioid prescription during follow-up. The
      sample was 61% men and 62% African American with a median age of 44.5 years. High
      risk opioid use occurred among 30% of incident opioid users (high daily dosage:
      7.9%; early refills: 15.9%; overlapping prescriptions: 16.4%; and multiple
      prescribers: 19.7%). About half of the cumulative incidence of high-risk use
      occurred within 1 year of receiving an opioid prescription. After adjusting for
      study site, high-risk opioid use was greater among patients with injection drug
      use as an HIV risk factor [adjusted hazard ratio (aHR) = 1.39, 95% confidence
      interval: 1.11 to 1.74], non-Hispanic whites [aHR = 1.61, (1.21 to 2.14)],
      patients age 35-45 [aHR = 1.94, (1.33 to 2.80)] and 45-55 [aHR = 1.84, (1.27 to
      2.67)], and patients with a diagnosis of chronic pain [aHR = 1.32, (1.03 to
      1.70)]. CONCLUSIONS: A large proportion of PLWH received opioid prescriptions,
      and among these opioid recipients, high-risk opioid use was common. High-risk use
      patterns often occurred within the first year, suggesting this is a critical time
      for intervention.

PMID- 29601406
TI  - Sex Differences in Subclinical Coronary Atherosclerotic Plaque Among Individuals
      With HIV on Antiretroviral Therapy.
AB  - BACKGROUND: In high-resource settings, the HIV-attributable risk of myocardial
      infarction (MI) is higher among women than among men. The extent to which unique
      mechanisms contribute to MI risk among women vs. men with HIV remains unclear.
      METHODS: Subclinical coronary atherosclerotic plaque characteristics-including
      high-risk morphology plaque features-were compared among 48 HIV-infected women
      [48 (41, 54) years] and 97 HIV-infected men [48 (42, 52) years] on stable
      antiretroviral therapy (ART) without known cardiovascular disease. These
      individuals had previously completed coronary computed tomography angiography and
      metabolic/immune phenotyping as part of a prospective study. RESULTS: Extending
      previous analyses, now focusing exclusively on ART-treated participants, we found
      that HIV-infected women had a lower prevalence of any subclinical coronary
      atherosclerotic plaque (35% vs. 62%, P = 0.003) and a lower number of segments
      with plaque (P = 0.01), compared with HIV-infected men. We also report for the
      first time that ART-treated HIV-infected women had a lower prevalence of high
      risk positively remodeled plaque (25% vs. 51%, P = 0.003) and a lower number of
      positively remodeled plaque segments (P = 0.002). In models adjusting for
      cardiovascular risk factors, we further showed that male sex remained associated
      with any coronary plaque [odds ratio 3.8, 95% confidence interval: (1.4 to 11.4)]
      and with positively remodeled plaque [odds ratio 3.7, 95% confidence interval:
      (1.4, 10.9)]. CONCLUSIONS: ART-treated HIV-infected women (vs. HIV-infected men)
      had a lower prevalence and burden of subclinical coronary plaque and high-risk
      morphology plaque. Thus, unique sex-specific mechanisms beyond subclinical plaque
      may drive the higher HIV-attributable risk of MI among women vs. men.

PMID- 29601407
TI  - Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients
      With Psychotic Mood Disorders.
AB  - BACKGROUND: The aim of the present study was to appraise retrospectively the
      influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma
      concentrations of clozapine (CLZ), the prototype of various second-generation
      antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio
      (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of
      bipolar disorder were studied. We then analyzed data altogether and subdivided
      them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2
      CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n
      = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels
      (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of
      body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P <
      0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log
      transformed them, and performed analysis of variance factor analyses followed by
      pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We
      identified significant drug effects on (1) CLZ plasma levels, significantly
      higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2
      versus groups #1 and #3. Significant drug * gender interactions were observed in
      group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with
      women. CONCLUSIONS: Despite its inherent limitations, this observational study
      confirms the significant increase in plasma CLZ concentrations and reduction in
      NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect
      apparently counteracted by VPA (group #4). The drug * gender interactions in
      patients taking both CLZ and VPA (group #3) warrant further prospective study.

PMID- 29601408
TI  - Microanatomical Nerve Architecture of 6 Mammalian Species: Is Trans-Species
      Translational Anatomic Extrapolation Valid?
AB  - BACKGROUND AND OBJECTIVES: Various animal models have historically been used to
      study iatrogenic nerve injury during performance of conduction nerve blocks. Our
      aims were to compare the microstructures of nerves in commonly used species to
      those of humans and to explore the validity of the extrapolating these findings
      to humans. METHODS: High-resolution, light-microscopic images were obtained from
      cross sections of sciatic nerves at their bifurcation from fresh rat, rabbit,
      pig, sheep, dog, and human cadavers. Various microanatomical characteristics were
      measured and compared between the species. P < 0.0033 indicated significant
      differences. RESULTS: Forty-four samples were studied. There were some
      interspecies similarities, but the majority of the microanatomical measurements
      of all 5 species differed significantly from those of humans. Exceptions were rat
      fascicle cross-sectional area (P = 0.367) and fascicle circumference (P = 0.396);
      ratio of dog, pig, and sheep fascicle area to total nerve area (dog: P = 0.350;
      pig: P = 0.958; sheep: P = 0.052); and number of fascicles (pig: P = 0.454; sheep
      P = 0.077). CONCLUSIONS: Although some of the metrics could reasonably be
      expected to differ because of the size of the species-for example, nerve cross
      sectional area-there was little microanatomical similarity between the sciatic
      nerves of humans and those of the nonprimate mammalian species studied. This may
      question the validity of some conclusions reached over the years by direct
      translation from these species to humans. Further studies on nerve function,
      intraneural injection, and microanatomy of nonhuman primate species are
      warranted.

PMID- 29601409
TI  - Correlation of MRI-derived adipose tissue measurements and anthropometric markers
      with prevalent hypertension in the community.
AB  - OBJECTIVES: To compare the correlations of MRI-derived adipose tissue
      measurements and anthropometric markers, respectively, with prevalent
      hypertension in a community-based sample, free of clinical cardiovascular
      disease. METHODS: MRI-derived adipose tissue measurements were obtained in 345
      participants (143 women; age 39-73 years) of the KORA FF4 survey from Southern
      Germany using a 3-Tesla machine and included total adipose tissue (TAT), visceral
      adipose tissue (VAT), subcutaneous adipose tissue (SCAT), hepatic fat fraction
      (HFF), pancreatic fat fraction (PFF) as well as pericardial adipose tissue (PAT).
      In addition, the anthropometric markers body mass index, waist circumference, hip
      circumference, waist-hip ratio (WHR) and waist-height ratio (WHtR) as well as
      blood pressure measurements were obtained. RESULTS: The prevalence of
      hypertension was 33.6% (women: 28%, men: 38%). VAT and PAT had the highest area
      under the curve (AUC) values for identifying individuals with prevalent
      hypertension (AUC: 0.75; 0.73, respectively), whereas WHtR and waist
      circumference were best performing anthropometric markers (AUC: 0.72; 0.70,
      respectively). A 1SD increment of TAT was associated with the highest odd for
      hypertension in the age-adjusted and sex-adjusted model (OR = 2.20, 95% CI 1.67
      2.91, P < 0.001) and in the fully adjusted model (OR = 1.97, 95% CI 1.45-2.66, P
      < 0.001). TAT was the only MRI-derived adipose tissue measurement that was
      associated with hypertension independently of the best performing anthropometric
      marker waist circumference in the fully adjusted model (OR = 1.93, 95% CI 1.00
      3.72, P = 0.049). CONCLUSION: MRI-derived adipose tissue measurements perform
      similarly in identifying prevalent hypertension compared with anthropometric
      markers. Especially, TAT, VAT and PAT as well as WHtR and waist circumference
      were highly correlated with prevalent hypertension.

PMID- 29601410
TI  - Increased aortic wave reflection contributes to higher systolic blood pressure in
      adolescents born preterm.
AB  - OBJECTIVE: To evaluate the wave reflection characteristics in the aortic arch and
      common carotid artery of ex-preterm adolescents and assess their relationship to
      central blood pressure in a cohort followed prospectively since birth. METHODS:
      Central blood pressures, pulse wave velocity, augmentation index, microvascular
      reactive hyperemia, arterial distensibility, compliance and stiffness index, and
      also aortic and carotid wave intensity were measured in 18-year-olds born
      extremely preterm at below 28 weeks' gestation (n = 76) and term-born controls (n
      = 42). RESULTS: Compared with controls, ex-preterm adolescents had higher central
      systolic (111 +/- 11 vs. 105 +/- 10 mmHg; P < 0.001) and diastolic blood
      pressures (73 +/- 7 vs. 67 +/- 7 mmHg; P < 0.001). Although conventional measures
      of arterial function and biomechanics such as pulse wave velocity and
      augmentation index were no different between groups, wave intensity analysis
      revealed elevated backward compression wave area (-0.39 +/- 0.21 vs. -0.29 +/-
      0.17 W/m/s * 10; P = 0.03), backward compression wave pressure change (9.0 +/-
      3.5 vs. 6.6 +/- 2.5 mmHg; P = 0.001) and reflection index (0.44 +/- 0.15 vs. 0.32
      +/- 0.08; P < 0.001) in the aorta of ex-preterm adolescents compared with
      controls. These changes were less pronounced in the carotid artery. On
      multivariable analysis, forward and backward compression wave areas were the only
      biomechanical variables associated with central systolic pressure. CONCLUSIONS:
      Ex-preterm adolescents demonstrate elevated wave reflection indices in the aortic
      arch, which correlate with central systolic pressure. Wave intensity analysis may
      provide a sensitive novel marker of evolving vascular dysfunction in ex-preterm
      survivors.

PMID- 29601411
TI  - Antihypertensive drug use in resistant and nonresistant hypertension and in
      controlled and uncontrolled resistant hypertension.
AB  - BACKGROUND AND AIM: Treatment-resistant hypertension (TRH) is associated with
      particular clinical features, nonadherence, and suboptimal treatment. We assessed
      possible associations of antihypertensive drug classes, specific agents inside
      each class, and types of combinations, with the presence of non-TRH vs. TRH, and
      with controlled vs. uncontrolled TRH. METHODS: Comparisons were done in 14 264
      patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974
      treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591).
      Associations were adjusted for age, sex, and previous cardiovascular event.
      RESULTS: In both groups of patients treated with three or with at least four
      drugs, aldosterone antagonists among drug classes [adjusted odds ratio (OR): 1.82
      and 1.41, respectively], and ramipril (OR: 1.28 and 1.30), olmesartan (OR: 1.31
      and 1.37), and amlodipine (OR: 1.11 and 1.41) inside each class were
      significantly associated with blood pressure control (non-TRH or controlled TRH).
      In patients treated with three drugs, non-TRH was also associated with the use of
      chlorthalidone (OR: 1.50) and bisoprolol (OR: 1.19), whereas in patients treated
      with at least four drugs, controlled TRH was significantly associated with the
      triple combination of a renin-angiotensin system blocker, a calcium channel
      blocker, and a diuretic (OR: 1.17). CONCLUSION: The use of aldosterone
      antagonists is associated with blood pressure control in patients treated with
      three or more drugs. Similar results are observed with specific agents inside
      each class, being ramipril, olmesartan, chlorthalidone, amlodipine, and
      bisoprolol those exhibiting significant results. An increased use of these drugs
      might probably reduce the burden of TRH.

PMID- 29601412
TI  - Left ventricular mass independently associates with masked hypertension in young
      healthy adults: the African-PREDICT study.
AB  - OBJECTIVE: Masked hypertension is reportedly common in young adults. However, it
      is unknown if these masked hypertensive individuals already present with organ
      damage. We determined whether a relationship exists between left ventricular
      structure and function, and masked hypertension in young healthy adults. METHODS:
      In this cross-sectional study, we included 774 black and white men and women
      (aged 20-30 years) who had successful ambulatory blood pressure monitoring
      readings (>70% valid readings) and valid echocardiography done. RESULTS: We found
      that 16.4% had masked hypertension (60.6% whites; 67.7% men). When performing
      multivariable-adjusted logistic regression, we found masked hypertensive patients
      to have higher odds to present with increased left ventricular mass index (odds
      ratio 1.67, P = 0.031) compared to normotensive individuals. In multivariable
      adjusted linear regression analyses, left ventricular mass index positively and
      independently associated with masked hypertension [adjusted R = 0.193, beta =
      0.08 (0.01; 0.16), P = 0.046]. However, we found no independent link between
      echocardiographic measures of left ventricular function and masked hypertension.
      CONCLUSION: This study highlights the importance of the early detection of masked
      hypertension as young apparently healthy adults already show an increased left
      ventricular mass index, thereby indicating increased risk for future
      cardiovascular disease.

PMID- 29601413
TI  - Masked hypertension and kidney function decline: the Jackson Heart Study.
AB  - BACKGROUND: Hypertension diagnosed by blood pressure (BP) measured in the clinic
      is associated with rapid kidney function decline (RKFD) and incident chronic
      kidney disease (CKD). The extent to which hypertension defined using out-of
      clinic BP measurements is associated with these outcomes is unclear. METHODS: We
      evaluated the association of any masked hypertension (daytime SBP/DBP >= 135/85
      mmHg, night-time SBP/DBP >= 120/70 mmHg or 24-h SBP/DBP >= 130/80 mmHg) with RKFD
      and incident CKD among 676 African-Americans in the Jackson Heart Study with
      clinic-measured SBP/DBP less than 140/90 mmHg who completed ambulatory BP
      monitoring in 2000-2004. RKFD was defined as a decline in estimated glomerular
      filtration rate (eGFR) at least 30% and incident CKD was defined as development
      of eGFR less than 60 ml/min per 1.73 m with an at least 25% decline in eGFR
      between 2000-2004 and 2009-2013. RESULTS: The mean age of participants was 57.6
      years, 28.8% were men and 52.7% had any masked hypertension. After a median
      follow-up of 8 years, 13.8 and 8.6% of participants had RKFD and incident CKD,
      respectively. In unadjusted analyses, masked hypertension was associated with an
      increased odds for incident CKD [odds ratio (OR) 2.20, 95% confidence interval
      (CI) 1.22, 3.97]. This association remained statistically significant after
      adjustment for demographic characteristics, baseline eGFR and albumin-to
      creatinine ratio (OR 1.95, 95% CI 1.04, 3.67) but was eliminated after propensity
      score adjustment (OR 1.62, 95% CI 0.87, 3.00). There was no association between
      masked hypertension and RKFD. CONCLUSION: Masked hypertension may be associated
      with the development of CKD in African-Americans.

PMID- 29601415
TI  - Aortic Root Sign.

PMID- 29601414
TI  - Feeling Safe and Taking on Responsibilities: Newly Graduated Nurses' Perceptions
      and Evaluations of Their Transition Into a Forensic Mental Health Inpatient
      Setting.
AB  - Forensic mental health care is faced with serious problems in the recruitment and
      retention of newly graduated nurses (NGNs). Research into NGNs' experiences of
      their transition to and evaluations of transition programs in forensic care is
      sparse, and more studies are called for. This study aimed to investigate the
      characteristics of NGNs' experiences and perceptions of their transition into a
      forensic setting and their evaluations of the introduction period. Three focus
      group interviews were carried out, involving 13 NGNs, lasting 79.68 minutes on
      average. They were analyzed using thematic analysis. Results show two main
      themes: "feeling safe" and "taking on responsibilities." If NGNs felt
      overburdened with clinical responsibilities during their transition, their
      feeling of safety reduced. The converse also applied; theThe safer they felt, the
      greater clinical responsibility they felt capable of handling. The more difficult
      the NGNs perceived the informal transition, the more unsafe they felt, and the
      more negatively they perceived the responsibilities placed upon them. Tailored
      programs designed to support both the informal and formal transitions are
      recommended, along with preceptorship, theoretical training, and role-based
      support, such as a shift manager, along with early introduction to conflict
      management and security measures.

PMID- 29601416
TI  - Free pre-operative clear fluids before day-surgery?: Challenging the dogma.

PMID- 29601417
TI  - What is more important, cost or effectiveness?

PMID- 29601418
TI  - Reply to: what is more important, cost or effectiveness?

PMID- 29601419
TI  - Intubation with cervical spine immobilisation: a comparison between the
      KingVision videolaryngoscope and the Macintosh laryngoscope: A randomised
      controlled trial.

PMID- 29601420
TI  - The trapezius plane block: a technique for regional anaesthesia of the
      superficial posterior thorax.

PMID- 29601421
TI  - Economic evaluation of bilateral sternal local anaesthetic infusions via multi
      hole catheters after cardiac surgery.

PMID- 29601422
TI  - To Exist as a Case Manager Is to Constantly Change; to Be Successful, You Must
      Constantly Adapt.
AB  - Change is inevitable whether in personal or professional lives. Case management
      practice is always evolving on the basis of the dynamic nature of the U.S. health
      care environment. Effective case managers are those who possess an adaptive mind
      set, recognize the importance to change to maintain success, and remain relevant.
      They also demonstrate a sense of accountability and responsibility for own
      learning, professional development, and acquisition of new skills and knowledge.
      This editorial discusses the nature of change and adaptation and presents key
      strategies for case managers to remain relevant and effective in dynamic practice
      environments.

PMID- 29601423
TI  - Managing the Social Determinants of Health: Part I: Fundamental Knowledge for
      Professional Case Management.
AB  - OBJECTIVES: PRIMARY PRACTICE SETTING(S):: Applicable to health and behavioral
      health settings, wherever case management is practiced. FINDING/CONCLUSION: The
      SDH pose major challenges to the health care workforce in terms of effective
      resource provision, health and behavioral health treatment planning plus
      adherence, and overall coordination of care. Obstacles and variances to needed
      interventions easily lead to less than optimal outcomes for case managers and
      their health care organizations. Possessing sound knowledge and clear
      understanding of each SDH, the historical perspectives, main theories, and
      integral dynamics, as well as creative resource solutions, all support a higher
      level of intentional and effective professional case management practice.
      IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Those persons and communities impacted
      most by the SDH comprise every case management practice setting. These clients
      can be among the most vulnerable and disenfranchised members of society, which
      can easily engender biases on the part of the interprofessional workforce. They
      are also among the costliest to care for with 50% of costs for only 5% of the
      population. Critical attention to knowledge about managing the SDH leverages and
      informs case management practice, evolves more effective programming, and
      enhances operational outcomes across practice settings.

PMID- 29601424
TI  - An Acuity Tool for Heart Failure Case Management: Quantifying Workload, Service
      Utilization, and Disease Severity.
AB  - PURPOSE: The cardiology service line director at a health maintenance
      organization (HMO) in Washington State required a valid, reliable, and practical
      means for measuring workloads and other productivity factors for six heart
      failure (HF) registered nurse case managers located across three geographical
      regions. The Kilgore Heart Failure Case Management (KHFCM) Acuity Tool was
      systematically designed, developed, and validated to measure workload as a
      dependent function of the number of heart failure case management (HFCM) services
      rendered and the duration of times spent on various care duties. PRIMARY PRACTICE
      SETTING: Research and development occurred at various HMO-affiliated internal
      medicine and cardiology offices throughout Western Washington. The concepts,
      methods, and principles used to develop the KHFCM Acuity Tool are applicable for
      any type of health care professional aiming to quantify workload using a high
      quality objective tool. The content matter, scaling, and language on the KHFCM
      Acuity Tool are specific to HFCM settings. METHODOLOGY AND SAMPLE: The content
      matter and numeric scales for the KHFCM Acuity Tool were developed and validated
      using a mixed-method participant action research method applied to a group of six
      outpatient HF case managers and their respective caseloads. The participant
      action research method was selected, because the application of this method
      requires research participants to become directly involved in the diagnosis of
      research problems, the planning and execution of actions taken to address those
      problems, and the implementation of progressive strategies throughout the course
      of the study, as necessary, to produce the most credible and practical practice
      improvements (; ; ; ). Heart failure case managers served clients with New York
      Heart Association Functional Class III-IV HF (), and encounters were conducted
      primarily by telephone or in-office consultation. RESULTS: A mix of qualitative
      and quantitative results demonstrated a variety of quality improvement outcomes
      achieved by the design and practice application of the KHFCM Acuity Tool. Quality
      improvement outcomes included a more valid reflection of encounter times and
      demonstration of the KHFCM Acuity Tool as a reliable, practical, credible, and
      satisfying tool for reflecting HF case manager workloads and HF disease severity.
      IMPLICATIONS: The KHFCM Acuity Tool defines workload simply as a function of the
      number of HFCM services performed and the duration of time spent on a client
      encounter. The design of the tool facilitates the measure of workload, service
      utilization, and HF disease characteristics, independently from the overall
      measure of acuity, so that differences in individual case manager practice, as
      well as client characteristics within sites, across sites, and potentially
      throughout annual seasons, can be demonstrated. Data produced from long-term
      applications of the KHFCM Acuity Tool, across all regions, could serve as a
      driver for establishing systemwide HFCM productivity benchmarks or standards of
      practice for HF case managers. Data produced from localized applications could
      serve as a reference for coordinating staffing resources or developing HFCM
      productivity benchmarks within individual regions or sites.

PMID- 29601425
TI  - Predicting Risk Factors for 30-Day Readmissions Following Discharge From Post
      Acute Care.
AB  - PURPOSE OF STUDY: The specific aims of this descriptive study were to (1) examine
      the relationships between individual-level determinants of health using standard
      care admission assessments of residents admitted to a skilled nursing facility
      (SNF) and those residents readmitted to the hospital within 30 days from
      discharge from the same SNF; (2) identify and describe the risk factors of the
      residents readmitted to the hospital within 30 days; and (3) use the findings to
      inform and refine current practice to target the mutable risk factors correlated
      with 30-day hospital readmission. PRIMARY PRACTICE SETTING: A 180-bed skilled
      nursing center in Northeastern Pennsylvania. METHODOLOGY AND SAMPLE: A
      retrospective paper medical record review of patients discharged from an SNF to
      community living was conducted to examine the relationship between individual
      determinants of health behaviors and 30-day hospital readmissions. The study
      sample (N = 221) included adults 65 years and older who were admitted to the SNF
      from January to December 2014 for subacute physical rehabilitation following an
      acute care hospital stay with a discharge plan to community living. RESULTS: The
      30-day readmission rate was 11%. The results of the logistic regression including
      diagnosis at readmission showed that the odds of readmission before 30 days were
      nearly three times greater in patients who had congestive heart failure (p <
      .02). Patients who were at "very high risk" on the Braden Scale were 20 times
      more likely to be readmitted before 30 days compared with those at low risk. Age
      and gender were not predictors. None of the other standard screening assessments
      for delirium, depression, functional status, and fall risk were predictive of 30
      day readmission. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: (1) Care coordination
      and communication with residents, caregivers, and home health can have an impact
      on 30-day readmissions post-SNF discharge. (2) Chronic respiratory diseases
      continue to be a challenge in prevention of hospital readmissions.

PMID- 29601426
TI  - The Integrated Case Management Program: Essential for Today's Case Manager.

PMID- 29601427
TI  - Continuing Professional Education-Effective or Outdated?

PMID- 29601428
TI  - Legal Update: What Is the Purpose of the Rule?

PMID- 29601429
TI  - What Comes Next?: Looking Beyond the Clinical to the Vocational.

PMID- 29601431
TI  - Managing the Social Determinants of Health: Part I-Fundamental Knowledge for
      Professional Case Management.

PMID- 29601430
TI  - Breast-Feeding and Practice Tips for Case Managers.

PMID- 29601432
TI  - An Acuity Tool for Heart Failure Case Management: Quantifying Workload, Service
      Utilization, and Disease Severity.

PMID- 29601433
TI  - Thiopurine Optimization Through Combination With Allopurinol in Children With
      Inflammatory Bowel Diseases.
AB  - OBJECTIVES: Thiopurines are commonly used in the maintenance of remission for
      children with inflammatory bowel diseases (IBDs). Variation in drug metabolism
      may affect hepatotoxicity or therapeutic effect. We aimed to describe our
      center's experience with thiopurine optimization through the use of reduced
      thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug
      metabolite levels, and clinical outcomes in children with IBD. METHODS: Patients
      aged 2 to 21 years with IBD treated with the combination of
      thiopurines/allopurinol between 2008 and 2015 were retrospectively reviewed.
      Patients previously treated with antitumor necrosis factor therapy were excluded.
      Demographic data, transaminase levels (aspartate transaminase, alanine
      transaminase), drug metabolites levels (6-thioguanine [6-TG], 6
      methylmercaptopurine), physician global assessment, and corticosteroid use were
      recorded at baseline, 6, and 12 months. RESULTS: Fifty-two patients (29 girls,
      56%) met inclusion criteria. Thirty-two of 52 (62%) remained on the combination
      for 12 months. In those remaining on the thiopurine/allopurinol combination,
      median alanine transaminase and aspartate transaminase levels were reduced (P <
      0.001) and median 6-TG levels were increased (P < 0.001) at both 6 and 12 months.
      Corticosteroid use was decreased at both 6 (P < 0.001) and 12 months (P < 0.001)
      compared to use at baseline. Remission rates also improved at both 6 (P = 0.013)
      and 12 months (P = 0.003). Twenty of the 52 patients (38%) had discontinued the
      thiopurine/allopurinol combination within 12 months of initiation with 17 of 52
      (33%) initiating antitumor necrosis factor therapy. CONCLUSIONS: Low-dose
      thiopurines in combination with allopurinol improved hepatotoxicity and increased
      6-TG levels in children with IBD. Corticosteroid use was reduced and remission
      rates improved in those patients remaining on this combination for 1 year.
      However, approximately 40% of patients required a change in therapy within 12
      months.

PMID- 29601434
TI  - Pediatric Collagenous Gastritis and Colitis: A Case Series and Review of the
      Literature.
AB  - INTRODUCTION: Collagenous gastritis is a rare disease characterized by the
      subepithelial deposition of collagen bands. Two phenotypes of the disease have
      been described: a pediatric-onset and an adult-onset type. The adult-onset form
      is associated with collagenous colitis and autoimmune disorders. No effective
      treatment has been identified to date. OBJECTIVE: We aim to describe the clinical
      features and outcomes of patients in our cohort and provide a summary of
      published pediatric cases with collagenous gastritis and colitis reported to date
      to gather information that will contribute to improved knowledge of this rare
      condition. METHODS: A retrospective chart review of all patients with collagenous
      gastritis and/or colitis who were treated at the Royal Children's Hospital,
      Melbourne, was performed. A literature review was also conducted. RESULTS: A
      total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%)
      patients had associated collagenous colitis. The most common clinical
      presentation was iron deficiency anemia. Nine (75%) patients were followed up,
      and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved
      in all patients on oral iron supplementation. Histologic improvement was only
      identified in one patient with the adult phenotype who had been treated with oral
      corticosteroids and azathioprine. CONCLUSIONS: Collagenous gastritis is a rare
      condition in children. A small proportion of children develop features of the
      "'adult" phenotype at a very young age. Patients with collagenous gastritis
      require long-term follow-up and monitoring of their disease. Further randomized
      clinical trials are needed to establish an effective therapeutic strategy.

PMID- 29601435
TI  - Multivariate Model for the Prediction of Severity of Acute Pancreatitis in
      Children.
AB  - This study aimed to develop a severity prediction system for pediatric patients
      with acute pancreatitis (AP) based on clinical and laboratory parameters recorded
      at disease onset. A retrospective cohort study including 130 patients with AP,
      aged 0 to 18 years, was conducted. Correlations between severe AP (SAP) and
      clinical and laboratory data were established. Parameters with a significant
      statistical correlation (P <= 0.05) were incorporated in logistic regression
      models, and receiver operating characteristic curves were generated. The best
      performance cutoff points were calculated to propose a severity prediction score,
      for which sensitivity and specificity were determined. Thirty-eight cases (29.2%)
      were consistent with SAP. A value of >=1 point yielded a sensitivity of 81.5% and
      specificity of 64.1% for SAP prediction, when using a score including blood urea
      nitrogen >=12.5 mg/dL (1 point) or hemoglobin <13 mg/dL (1 point) as variables.
      The proposed severity score showed good performance in predicting SAP.

PMID- 29601436
TI  - Gavage Feed Volume Determines the Gastric Emptying Rate in Preterm Infants.
AB  - OBJECTIVE: Feeding intolerance, manifesting as increased gastric residual, is a
      common finding in preterm neonates. Little is known about the regulation of
      gastric emptying early in life and the extent to which this plays a role in the
      preterm infants' feeding tolerance. The goal of this study was to evaluate
      clinically stable 28- to 32-week gestation neonates during the first 4 weeks of
      life and noninvasively determine their gastric emptying rate. STUDY DESIGN:
      Ultrasound measurements of gastric milk content volume were obtained from 25
      neonates immediately after, 30 and/or 60 minutes following routine gavage feeds.
      The content emptying rate was calculated from the gastric volume data. RESULTS:
      Gastric emptying rate was not postnatal age-dependent, was significantly higher
      at 30 minutes, whenever compared with 60-minute postfeed and directly
      proportional to the feed volume. At any postnatal age, the gastric emptying rate
      was at least 6-fold greater, when comparing the lowest and highest average
      stomach content volumes. CONCLUSIONS: The gastric emptying rate of preterm
      infants is content volume-dependent and unrelated to the postnatal age. Given the
      present findings, further investigation on the gastric residual of preterm
      infants receiving larger than currently administered feed volumes at the
      initiation of enteral nutrition, is warranted.

PMID- 29601437
TI  - Detection of Cytomegalovirus in Colonic Mucosa of Children With Inflammatory
      Bowel Disease: Inflammatory Bowel Disease.
AB  - OBJECTIVES: Although it has been recommended to perform sigmoidoscopy to screen
      for cytomegalovirus (CMV) reactivation in acute severe colitis, the frequency of
      CMV reactivation in children with inflammatory bowel disease (IBD) is unknown.
      The aim of this study was to determine the frequency and management of CMV
      detection in colonic mucosa of children with IBD. METHODS: In a retrospective
      study, consecutive IBD patients, <17 years old, with moderate to severe colitis
      who had sigmoid biopsy specimens evaluated for CMV by hematoxylin and eosin (H&E)
      staining, immunohistochemistry (IHC), and polymerase chain reaction (PCR) were
      included. RESULTS: A total of 90 sigmoid biopsies were collected from 67 patient
      encounters from 58 patients with colitis: 61 patient encounters (91%) with UC/IBD
      U including biopsy samples from colectomy specimens of eight patients who had
      colectomy during the study period. Medication exposure included corticosteroids
      for 40 (69%) patients, and immunosuppressive agents for 31 (53.4%) patients. Four
      of 61 patient encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory
      disease, had positive biopsies for CMV by PCR but negative H&E and IHC. They
      responded to escalated medical therapy, without needing anti-viral therapy, and
      none required colectomy over a median duration of follow up of 1.1 year (IQR 1
      1.6). CONCLUSIONS: CMV presence is uncommon in colonic mucosa of children with
      IBD. Studies examining the underlying sero-prevalence of CMV and its role of
      reactivation of colitis are required to determine if the current recommendation
      for routine sigmoidoscopy to exclude CMV infection in corticosteroid-refractory
      acute severe colitis is justified.

PMID- 29601438
TI  - Proton Pump Inhibitors and Infant Pneumonia/Other Lower Respiratory Tract
      Infections: National Nested Case-control Study.
AB  - OBJECTIVE: The possible association between the use of proton pump inhibitors
      (PPIs) and community-acquired pneumonia (CAP) or another lower respiratory tract
      infection (LRTI) remains uncertain. We conducted a nested case-control study
      using routinely collected national health and drug dispensing data in New Zealand
      to examine the risk of CAP or another LRTI resulting in hospitalization or death
      in infants dispensed a PPI. STUDY DESIGN: The cohort included 21,991 patients
      without a history of CAP or another LRTI who were born between 1 January 2005 and
      31 December 2012 and were dispensed omeprazole, lansoprazole, or pantoprazole
      (the PPIs available in New Zealand during the study period) on at least one
      occasion during the first year of life. Cases had a first diagnosis after cohort
      entry (first PPI dispensing) of CAP (n = 65) validated by hospital discharge
      letter or death record, and chest radiography; or LRTI (including CAP) (n = 566)
      validated by hospital discharge letter or death record, with or without chest
      radiography. Up to 10 controls, matched by sex and date of birth, were randomly
      selected for each case. We conducted complete case analyses for the fully
      adjusted models. RESULTS: In the adjusted analysis based on CAP cases and their
      controls, the matched odds ratio for current versus past use of PPIs was 0.88
      (95% confidence interval 0.36-2.16). For all LRTI cases and their controls, the
      matched odds ratio was 1.13 (0.87-1.48). CONCLUSION: In otherwise healthy
      community-dwelling infants, current use of a PPI does not appear to increase the
      risk of CAP or other LRTIs.

PMID- 29601439
TI  - Neurodevelopmental Outcomes in Children With Liver Diseases: a Systematic Review.
AB  - OBJECTIVE: The aim of the study was to determine the neurodevelopmental outcomes
      of children with liver diseases based on a systematical review of the literature.
      METHOD: A literature search according to the PRISMA statement was conducted using
      predefined search terms in PubMed, Cochrane Library, and PsycINFO. The inclusion
      criterion was studies published from 2000 onwards that reported on the
      neurodevelopmental outcomes of term-born children with liver diseases. A
      narrative synthesis was done to appraise the studies. RESULTS: Twenty-five
      studies were included (1913 children), 19 of which described children after liver
      transplantation (LTx; 1372 children). Sixty-seven percentage of the studies on
      children with liver diseases who survived with their native livers showed low
      average or abnormal scores on specific subscales of cognitive and behavioral
      measures. In studies on children after LTx, this was 82%. After LTx, 83% of
      studies demonstrated impaired outcomes on behavior, whereas 42% of children
      received special education. Motor development was impaired in 82% of studies in
      children with native liver and after LTx. LIMITATIONS: Studies were heterogenic
      because of sample sizes, etiology of liver disease and type of assessment tools
      used. CONCLUSIONS: More than two-third of included studies showed
      neurodevelopmental deficits in children with liver diseases, affecting all
      neurodevelopmental areas. Knowledge on risk factors for impaired neurodevelopment
      is limited and lack of long-term follow-up is worrying, especially considering
      the increasing survival rates, resulting in more at-risk patients. Studying early
      predictors and risk factors of abnormal developmental trajectories of children
      with liver diseases is indicated to assess strategies to improve their long-term
      neurodevelopmental outcomes.

PMID- 29601440
TI  - Celiac Diasease-associated lncRNA Named HCG14 Regulates NOD1 Expression in
      Intestinal Cells.
AB  - OBJECTIVE: The aim of the study is to identify additional celiac disease
      associated loci in the major histocompatibility complex (MHC) independent from
      classical HLA risk alleles (HLA-DR3-DQ2) and to characterize their potential
      functional impact in celiac disease pathogenesis at the intestinal level.
      METHODS: We performed a high-resolution single-nucleotide polymorphism (SNP)
      genotyping of the MHC region, comparing HLA-DR3 homozygous celiac patients and
      non-celiac controls carrying a single copy of the B8-DR3-DQ2 conserved extended
      haplotype. Expression level of potential novel risk genes was determined by RT
      PCR in intestinal biopsies and in intestinal and immune cells isolated from
      control and celiac individuals. Small interfering RNA-driven silencing of
      selected genes was performed in the intestinal cell line T84. RESULTS: MHC
      genotyping revealed 2 associated SNPs, one located in TRIM27 gene and another in
      the non-coding gene HCG14. After stratification analysis, only HCG14 showed
      significant association independent from HLA-DR-DQ loci. Expression of HCG14 was
      slightly downregulated in epithelial cells isolated from duodenal biopsies of
      celiac patients, and eQTL analysis revealed that polymorphisms in HCG14 region
      were associated with decreased NOD1 expression in duodenal intestinal cells.
      CONCLUSIONS: We have successfully employed a conserved extended haplotype
      matching strategy and identified a novel additional celiac disease risk variant
      in the lncRNA HCG14. This lncRNA seems to regulate the expression of NOD1 in an
      allele-specific manner. Further functional studies are needed to clarify the role
      of HCG14 in the regulation of gene expression and to determine the molecular
      mechanisms by which the risk variant in HCG14 contributes to celiac disease
      pathogenesis.

PMID- 29601441
TI  - The Membrane-bound O-Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic
      Fatty Liver Disease.
AB  - BACKGROUND: The rs641738 polymorphism in the membrane-bound O-acyltransferase
      domain containing protein 7 (MBOAT7) gene has been associated with increased risk
      of nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: To investigate the
      association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis
      and biochemical markers of liver damage and to evaluate the potential additive
      effect of this variant and the I148M patatin-like phospholipase domain-containing
      3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2)
      polymorphisms. METHODS: One thousand and 2 obese children were genotyped for
      MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical,
      ultrasonographic, and biochemical evaluation. Indirect measurement of liver
      fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from
      these polymorphisms were calculated. RESULTS: Carriers of the MBOAT7 T allele
      showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P =
      0.04) than noncarriers. These findings were confirmed also for the carriers of
      the MBOAT7 T allele polymorphism with hepatic steatosis compared with
      noncarriers. A higher genetic risk score was associated with higher ALT (P =
      0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3-5.5, P
      = 0.003). Patients belonging to genetic risk score 3 group had an OR to present
      steatosis of 2.6 (95% CI 1.43-4.83, P = 0.0018) compared with those belonging to
      lower genetic risk score group. CONCLUSIONS: We first demonstrated in childhood
      obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined
      effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided
      the first pediatric association of the MBOAT7 polymorphism with indirect markers
      of liver fibrosis.

PMID- 29601442
TI  - Early Administration of N-acetylcysteine in the Treatment of Clove Oil Ingestion.

PMID- 29601443
TI  - Yield and Examiner Dependence of Digital Rectal Examination in Detecting
      Impaction in Pediatric Functional Constipation.
AB  - OBJECTIVES: Guidelines on functional constipation recommend digital rectal
      examination (DRE) when constipation is doubtful or with a suspicion of organic
      etiology. The guidelines do not clarify if DRE is mandatory to diagnose
      impaction. This study aims to determine the frequency of impaction detectable
      only on DRE among children satisfying Rome III criteria without requiring DRE and
      also the inter-observer influences on impaction detection by DRE. METHODS:
      Children between 6 months to 13 years of age, presenting with history suggestive
      of constipation were assessed. After excluding those with suspicion of organic
      etiology, those who needed DRE for diagnosis of constipation and those who do not
      satisfy Rome III criteria without DRE, the rest who satisfied Rome III criteria
      were assessed for impaction by palpable fecoliths or constipation-associated
      fecal incontinence. Those without such impaction were randomized to 2 examiners
      for DRE to diagnose impaction, in the absence of contraindications. RESULTS: Two
      hundred and thirty-three children were assessed. One hundred and sixty-nine
      satisfied Rome III without needing DRE. Forty-eight (28.4%) had impaction
      detectable without DRE. Among the rest, 28 (30.1%) had impaction by DRE. There
      was no difference between the frequency of impaction detected by the 2 examiners.
      Clinical characteristics were similar (P > 0.05) between those with impaction
      detectable by DRE and those without. CONCLUSIONS: DRE does detect cases of
      impaction not discernible by other means. Such a finding may be comparable
      between examiners. These children may be identified by other clinical
      characteristics. The clinical significance of such a finding needs more
      understanding from the standpoint of therapeutic choices.

PMID- 29601444
TI  - Tribute to the unknown nurse.

PMID- 29601445
TI  - Article Summaries for April 2018 Psychosomatic Medicine, Volume 80, Issue 3.

PMID- 29601446
TI  - Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and
      Fecal Microbiota Transplantation in a Pediatric Hospital.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is one of the most common
      nosocomial infections in the United States, with an increasing incidence in
      children. Approximately 20% of pediatric patients develop recurrent infections.
      It's imperative to further analyze the incidence of recurrent CDI in the
      pediatric population and determine the most effective treatments. The primary
      goal of this study is to characterize children with recurrent CDI at our
      institution, including both hospital-acquired (HA-CDI) and community-acquired (CA
      CDI) cases, summarize the various treatments utilized, including fecal microbiota
      transplant (FMT), and compare their success rates. METHODS: A retrospective
      cohort study of pediatric patients aged 1-21 years treated for CDI at a single
      institution from January 2010 - December 2014 was performed. RESULTS: There were
      175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most
      common initial treatment (145/207, 70%) followed by oral vancomycin (30/207,
      15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty
      nine percent (63/215) of all initial CDI cases had at least one documented
      recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less
      likely to recur than those with CA-CDI (OR: 0.39; 95% CI: 0.18-0.85; p=0.018).
      The overall success rate for FMT at our institution was 10/12 (83%). CONCLUSIONS:
      Our data show cases of HA-CDI were less likely to recur compared with CA-CDI.
      Though currently reserved for multiply-recurrent cases, FMT was highly successful
      in our small cohort. More studies on FMT should be conducted to further evaluate
      its usefulness in the treatment of recurrent CDI in children.

PMID- 29601447
TI  - Itraconazole Dosing and Drug Monitoring at a Tertiary Children's Hospital.
AB  - BACKGROUND: Itraconazole is a broad-spectrum antifungal agent used for
      prophylaxis and treatment of fungal infections in immunocompromised children.
      Achieving the recommended target serum itraconazole trough concentration of >=0.5
      mg/L is challenging in children due to variation in itraconazole pharmacokinetics
      with age. We studied itraconazole use and treatment outcomes in a tertiary
      children's hospital. METHODS: We did a ten-year retrospective review of medical
      records of children at the Royal Children's Hospital Melbourne who received oral
      itraconazole and had therapeutic drug monitoring (TDM). RESULTS: Overall, 81
      children received 92 courses of oral itraconazole and had TDM. Of 222 TDM
      samples, 183 (82.4%) were taken at the appropriate time (trough level at steady
      state). Patients aged <=12 years and >12 years required median doses of 6.2 and
      3.9 mg/kg/day respectively to attain target trough levels(p<0.001). Of children
      aged <=12 years, 71.4% required doses above the recommended dose of 5 mg/kg/day
      to achieve therapeutic levels, compared to 17.4% of those aged >12 years. At
      least one sub-therapeutic trough concentration was reported in 63 (76.8%)
      courses; in only 18 (28.6%) of these was the dose adjusted. Gastrointestinal
      symptoms (14/92 (15.2%) courses) and hepatotoxicity (6/92 (6.5%)) were the most
      frequent adverse events. Neither were associated with elevated trough levels.
      CONCLUSIONS: The poor attainment of target levels with current recommended dosing
      in children aged <12 years suggests higher empiric doses are needed in this age
      group. The poor compliance with TDM guidelines highlights the need for better
      education about appropriate timing of sampling and dose adjustment.

PMID- 29601448
TI  - Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory
      Tract Infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower
      respiratory tract infections (LRTI) during the first year of life. Antibiotic
      treatment is recommended in cases suspected of bacterial coinfection. The aim of
      this prospective study was to estimate the incidence of bacterial coinfections
      and the amount of antibiotic overuse in children infected with RSV using expert
      panel diagnosis. METHODS: Children 1 month of age and over with LRTI or fever
      without source were prospectively recruited in hospitals in the Netherlands and
      Israel. Children with confirmed RSV infection by Polymerase Chain Reaction (PCR)
      on nasal swabs were evaluated by an expert panel as reference standard diagnosis.
      Three experienced pediatricians distinguished bacterial coinfection from simple
      viral infection using all available clinical information, including all
      microbiologic evaluations and a 28-day follow-up evaluation. RESULTS: A total of
      188 children (24% of all 784 recruited patients) were positive for RSV. From
      these, 92 (49%) were treated with antibiotics. All 27 children (29%) with
      bacterial coinfection were treated with antibiotics. Fifty-seven patients (62%)
      were treated with antibiotics without a diagnosis of bacterial coinfection. In 8
      of the 92 (9%), the expert panel could not distinguish simple viral infection
      from bacterial coinfection. CONCLUSION: This is the first prospective
      international multicenter RSV study using an expert panel as reference standard
      to identify children with and without bacterial coinfection. All cases of
      bacterial coinfections are treated, whereas as many as one-third of all children
      with RSV LRTI are treated unnecessarily with antibiotics.

PMID- 29601449
TI  - Antifungal Treatment and Outcome in Very Low Birth Weight Infants: A Population
      based Observational Study of the German Neonatal Network.
AB  - BACKGROUND: The diagnostic proof of fungal infection in preterm infants is
      difficult. Antifungal treatment (AFT) is often initiated empirically when infants
      with suspected infection do not improve despite broad-spectrum antibiotic
      therapy. It was the aim of our study to determine the rate of exposure to
      empirical AFT in a large cohort of very low birth weight infants (VLBWI) of the
      German Neonatal Network and to address associated risks and outcomes. METHODS:
      The epidemiologic database consisted of n = 13,343 VLBWI born in 54 German
      Neonatal Network centers between 2009 and 2015. AFT was defined as number of
      neonates who got any dose of at least one of the following antifungal drugs:
      fluconazole, amphotericin B, voriconazole and caspofungin (denominator: number of
      infants enrolled in German Neonatal Network) for treatment (not prophylaxis) of
      (suspected) fungal infection. Univariate and logistic regression analyses were
      used to identify risk factors for exposure to AFT and associated short-term
      morbidities and long-term outcomes at 5-year follow-up. RESULTS: In our cohort,
      724 out of 13,343 (5.4%) VLBWI were exposed to empiric AFT and had a mean
      gestational age of 25.7 (+/-2.1) weeks. Forty-four out of 13,343 (0.3%) had
      proven bloodstream infection with Candida spp. The main risk factors for exposure
      to AFT were gestational age, postnatal steroid treatment, need for abdominal
      surgery and use of carbapenems. Notably, AFT was associated with adverse outcomes
      such as bronchopulmonary dysplasia [adjusted odds ratio (OR): 1.9; 95% confidence
      interval (CI): 1.6-2.3; P < 0.001) and retinopathy of prematurity requiring
      intervention (adjusted OR: 1.69; 95% CI: 1.3-2.3; P <0.001) but not mortality. In
      the subgroup of infants available for 5-year follow-up (n = 895), exposure to AFT
      was associated with a risk for cerebral palsy (adjusted OR: 2.79; 95% CI: 1.11
      7.04; P = 0.04) and intelligence quotient < 85 (adjusted OR: 2.07; 95% CI: 1.01
      4.28; P = 0.049). CONCLUSIONS: A significant proportion of VLBWI is exposed to
      AFT, specifically those born <26 weeks. Exposed infants were found to have a
      higher risk for adverse outcomes, which may reflect their significant
      vulnerability in general. Given the observational design of our study, it remains
      unclear whether potential side effects of empirical or target AFT itself
      contribute to adverse outcome. Future studies need to include risk-based
      strategies and stewardship programs to restrict the use of antifungal management
      in VLBWI.

PMID- 29601450
TI  - Campylobacter Concisus and Acute Gastroenteritis in Children: Lack of
      Association.
AB  - The role of Campylobacter concisus as a cause of acute gastroenteritis remains to
      be demonstrated. This prospective study includes 184 cases and 176 controls. It
      shows no evidence that C. concisus plays a role in acute gastroenteritis.
      Considering the very low prevalence in cases and controls, if there is an
      etiologic link, it would be moderate and difficult to demonstrate.

PMID- 29601451
TI  - Serum Levels of Syndecan-1 in Patients with Kawasaki Disease.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis with coronary
      artery lesions (CALs) being the major concern. Syndecan-1 (SDC-1) is a major core
      protein expressed on the glycocalyx of endothelial cells. Shed SDC-1 in serum is
      regarded as a biomarker for endothelial activation or damage. METHODS: In this
      study, we aimed to determine the serum levels of SDC-1 and evaluate the
      relationship between serum levels of SDC-1 and the CALs in the acute phase of KD.
      Serum SDC-1 levels were measured in 119 children with KD and in 43 healthy
      children as normal controls and in 40 children with febrile disease. All KD
      patients were administrated a single dose of intravenous immunoglobulin (IVIG)
      and aspirin P.O. within 10 days of KD onset. RESULTS: Serum levels of SDC-1, in
      addition to albumin and hemoglobin were significantly increased in patients with
      KD than in healthy controls and febrile controls. Furthermore, the serum levels
      of syndecan-1, albumin, and hemoglobin were significantly elevated in KD patients
      with CALs than those without CALs. Additionally, serum levels of SDC-1 were
      significantly correlated with levels of hemoglobin and serum albumin in patients
      with KD. After IVIG therapy, serum levels of interleukin (IL)-6, soluble cell
      adhesion molecules-1(sICAM-1), and resisitin were reduced while serum levels of
      SDC-1 were significantly increased in KD patients. CONCLUSION: SDC-1 serum levels
      may mirror vascular endothelial damage and inflammation in KD. This might be
      utilized as a potential novel target for coronary artery protection in KD
      patients.

PMID- 29601452
TI  - Hospital Acquired Infections in Children: A Latin American Tertiary Teaching
      Hospital 5-Year Experience.
AB  - Hospital acquired infections account for high mortality rates and hospital costs.
      We analyzed pediatric data from a tertiary teaching hospital and found that most
      of cases occurred in the intensive care unit and had significant association with
      invasive devices. Bloodstream infections were the main site of infection and Gram
      negative bacteria were the predominant etiology.

PMID- 29601453
TI  - Safety, Effectiveness, and Exposure-Response of Micafungin in Infants:
      Application of an Established Pharmacokinetics Model to Electronic Health
      Records.
AB  - Micafungin is used off-label in the United States to treat invasive candidiasis
      in neonates. We used an established pharmacokinetic model to determine micafungin
      exposures for 46 courses in 39 hospitalized infants. In this small cohort of
      infants, micafungin exposure was not associated with laboratory markers of liver
      toxicity, death, or failure of microbiological clearance.

PMID- 29601454
TI  - Bacterial Load and Molecular Markers Associated With Early-onset Group B
      Streptococcus: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: The natural history of neonatal group B Streptococcus (GBS) is poorly
      understood. Little is known about the bacterial factors influencing the
      transmission of GBS from mother to neonate, or the development of invasive early
      onset GBS disease (EOGBS) in colonized neonates. We reviewed whether bacterial
      load and molecular markers are associated with GBS vertical transmission and
      progression to EOGBS. METHODS: We searched Medline, Embase, Cochrane and Web of
      Science from inception to October 10, 2016, for observational studies in English.
      We also hand-searched reference lists of relevant publications and experts cross
      checked included studies. Two reviewers independently screened studies, extracted
      data and appraised the quality of included studies using the Quality in Prognosis
      Studies tool. We conducted random-effects meta-analyses where possible and
      narratively synthesized the evidence in text and tables. RESULTS: Seventeen
      studies were included from 1107 records retrieved from electronic databases and
      publication references. Meta-analyses of 3 studies showed that neonates colonized
      by serotype III had a higher risk of developing EOGBS than serotype Ia (pooled
      risk ratio: 1.51, 95% confidence interval: 1.12-2.03) and serotype II (risk
      ratio: 1.95, 95% confidence interval: 1.10-3.45). Eleven studies showed that in
      heavily colonized mothers, 2-3 times more neonates were colonized, and in heavily
      colonized neonates, up to 15 times more neonates had EOGBS, compared with light
      colonization. Most evidence was published before 2000 and was at risk of bias.
      CONCLUSIONS: Acknowledging the difficulty of natural history studies, well
      controlled studies are needed to assess the predictive value of pathogen subtype
      and heavy load; they may be useful for better-targeted prevention.

PMID- 29601455
TI  - Successful Treatment of a South African Pediatric Case of Acute Liver Failure
      Caused By Perinatal Transmission of Hepatitis B.
AB  - We report on the successful treatment of a South African infant with hepatitis B
      virus (HBV)-induced acute liver failure using lamivudine with no evidence of
      clinical resistance. Perinatal HBV transmission occurred despite timely HBV
      vaccination at 6, 10, and 14 weeks, as per South African vaccination schedule,
      highlighting the need to introduce the birth-dose HBV vaccine in South Africa.

PMID- 29601456
TI  - Infant Human Immunodeficiency Virus-free Survival in the Era of Universal
      Antiretroviral Therapy for Pregnant and Breastfeeding Women: A Community-based
      Cohort Study From Rural Zambia.
AB  - BACKGROUND: Lifelong antiretroviral therapy (ART) is now recommended for all
      human immunodeficiency virus (HIV)-infected pregnant and breastfeeding women;
      however, few have described overall infant outcomes in this new era for the
      prevention of mother-to-child HIV transmission (PMTCT). METHODS: As part of an
      assessment of PMTCT program impact, we enrolled a prospective cohort study in 4
      predominantly rural districts in Zambia. HIV-infected mothers and their newborns
      (<=30 days old) were recruited and followed at 6 weeks, 6 months and 12 months
      postpartum; infant specimens were tested via HIV DNA polymerase chain reaction.
      In Kaplan-Meier analyses, we estimated overall infant HIV-free survival and then
      stratified by district, community and maternal ART use. We investigated the
      relationship between community-level 12-month, self-reported maternal ART use and
      infant HIV-free survival via linear regression. RESULTS: From June 2014 to
      November 2015, we enrolled 827 mother-infant pairs in 33 communities. At 12
      months, small proportions of infants had died (2.8%), were HIV-infected (3.0%) or
      were lost to follow-up (4.3%). Overall, infant HIV-free survival was 99.0% [95%
      confidence interval (CI): 98.0%-99.5%] at 6 weeks, 97.5% (95% CI: 96.1%-98.4%) at
      6 months and 96.3% (95% CI: 94.8%-97.4%) at 12 months. Women reporting ART use at
      enrollment had higher infant HIV-free survival than those who did not (97.4% vs.
      89.0%, P = 0.01). Differences were noted at the district and site levels (P =
      0.01). In community-level analysis, no relationship was observed between 12-month
      infant HIV-free survival and self-reported maternal ART use (P = 0.65).
      CONCLUSION: Although encouraging, these findings highlight the need for rigorous
      monitoring and evaluation of PMTCT services at the population level.

PMID- 29601457
TI  - Longitudinal Association Between Human Parechovirus Central Nervous System
      Infection And Gross-motor Neurodevelopment in Young Children.
AB  - BACKGROUND: A paucity of studies investigated the association between human
      parechovirus (HPeV) central nervous system (CNS) infection and motor and
      neurocognitive development of children. This study describes the gross-motor
      function (GMF) in young children during 24 months after HPeV-CNS-infection
      compared with children in whom no pathogen was detected. METHODS: GMF of children
      was assessed with alberta infant motor scale, bayley scales of infant and toddler
      development or movement assessment battery for children. We conducted
      multivariate analyses and adjusted for age at onset, maternal education and time
      from infection. RESULTS: Of 91 included children, aged at onset <24 months, 11
      had HPeV-CNS-infection and in 47 no pathogen was detected. Nineteen children were
      excluded due to the presence of other infection, preterm birth or genetic
      disorder and in 14 children parents refused to consent for participation. We
      found no longitudinal association between HPeV-CNS-infection and GMF (beta = 
      0.53; 95%CI =-1.18 to 0.07; P = 0.11). At 6 months, children with HPeV-CNS
      infection had suspect GMF delay compared with the non-pathogen group (mean
      difference = 1.12; 95%CI =-1.96 to -0.30; P = 0.03). This difference disappeared
      during 24 months follow-up and, after adjustment for age at onset, both groups
      scored within the normal range for age. Maternal education and time from
      infection did not have any meaningful influence. CONCLUSION: We found no
      longitudinal association between HPeV-CNS-infection and GMF during the first 24
      months follow-up. Children with HPeV-CNS-infection showed a suspect GMF delay at
      6 months follow-up. This normalized during 24 month follow-up.

PMID- 29601458
TI  - Epidemiology and Clinical Relevance of Toxic Shock Syndrome in US Children.
AB  - INTRODUCTION: It is important for clinicians to recognize the contribution of
      toxic shock syndrome (TSS) to the overall burden of pediatric septic shock
      because the clinical features, optimal therapy and prognosis differ from non-TSS
      septic shock. METHODS: We analyzed cases of pediatric septic shock reported to
      the Pediatric Health Information Systems database between 2009 and 2013 to define
      the clinical and demographic characteristics of pediatric TSS in the United
      States. Using a validated International Classification of Diseases, 9th revision,
      coding strategy, we identified patients with infectious shock among inpatients
      age 1-18 years and classified cases of staphylococcal and streptococcal TSS for
      comparison with non-TSS cases. RESULTS: Of 8,226 cases of pediatric septic shock,
      909 (11.1%) were classified as TSS and 562 (6.8%) were possible TSS cases.
      Staphylococcal TSS represented the majority (83%) of TSS cases and occurred more
      commonly in females and at an older age. Compared with non-TSS septic shock, TSS
      had significantly lower fatality rates, disease severity and length of hospital
      stay and was present more often at the time of admission (P < 0.001 for each).
      Streptococcal TSS was associated with poorer outcomes than staphylococcal TSS.
      Treatment for TSS differed from non-TSS septic shock in use of more clindamycin,
      vancomycin and Intravenous Immunoglobulin and less need for vasopressors.
      CONCLUSIONS: Results demonstrate a significant contribution of TSS to the burden
      of pediatric septic shock in the United States. The findings emphasize the
      importance of inclusion of TSS diagnostic and therapeutic considerations in
      sepsis treatment protocols for children.

PMID- 29601459
TI  - Simplified Treatment of Possible Severe Bacterial Infection in Young Infants When
      Referral is not Feasible. What Happened There? What are the Implications Here?
AB  - Severe bacterial infections remain one of the three leading causes of newborn
      death world-wide. Most such deaths could be prevented with timely and appropriate
      antibiotic treatment. However in low-income countries, there are many such cases
      for which, practically speaking, it is not currently feasible to offer gold
      standard, in-patient treatment with 7 days of parenteral antibiotics. Recent
      trial results, however, provide evidence for efficacy using simpler out-patient
      antibiotic regimens, equivalent to treatment with 7 days of procaine penicillin
      and gentamicin, given on an outpatient basis. Based on these findings, the World
      Health Organization has recently released guidelines endorsing such an approach
      for cases for which referral for inpatient treatment is not feasible. This brief
      report looks beyond the measured effect sizes in the published trials to other
      details on how they were implemented and what outcomes were observed for
      different groups of study participants. The report considers, further, the
      circumstances in country settings where such a strategy may be appropriate and
      offers issues for consideration by policy makers.

PMID- 29601460
TI  - National Incidence of Pediatric Mastoiditis in the United States, 2000-2012:
      Creating a Baseline for Public Health Surveillance.
AB  - Between 2000-2012, the national estimated incidence rate of pediatric
      mastoiditis, a rare but serious complication of acute otitis media (AOM), was
      highest in 2006 (2.7 per 100,000 population) and lowest in 2012 (1.8 per 100,000
      population). This measure provides a baseline for public health surveillance in
      the pneumococcal conjugate vaccine era as stewardship efforts target antibiotic
      use in AOM.

PMID- 29601461
TI  - Pediatric Forefoot Fractures: Assessment of Fracture Patterns and Predictors of
      Complicated Outcome.
AB  - BACKGROUND: Forefoot fractures account for 6% to 10% of fractures in children,
      and although the majority heals with supportive treatment, complications may lead
      to pain and disability. No previous study in children has evaluated complication
      risk in the emergency department based on initial assessment characteristics.
      STUDY OBJECTIVES: The study aim was to identify the radiological and clinical
      variables that increase the complication rate of pediatric forefoot fractures.
      This may help emergency physicians refer patients who require more thorough
      follow-up or surgical intervention. METHODS: We evaluated 497 forefoot fractures
      on initial presentation to a pediatric emergency department at the Children's
      Hospital at London Health Science Centre over a 6-year period. We collected
      variables such as degree of angulation, displacement, number of concurrent
      fractures, and demographic data such as age and sex. We then determined the
      variables associated with complications by reviewing each patient's chart.
      RESULTS: Overall, there was a 6.4% complication rate. Analysis identified sex as
      an important predictor of complications. Females, although representing
      approximately one third of the sample, represented nearly two thirds of the cases
      with complicated outcomes (P = 0.001; odds ratio [OR], 4.67). Increased number of
      fractures was also significant (P = 0.01; OR, 2.41) as was increasing age (P =
      0.01; OR, 1.17) and patients who chose to return to the emergency department (P <
      0.05; OR, 5.282). Lateral angulation/displacement and anteroposterior
      angulation/displacement were not associated with increased complications.
      CONCLUSION: Identifying features, such as female sex, increasing age, multiple
      fractures, and return to emergency departments for repeat visits, may help guide
      the emergency physician on whom to refer for specialized care.

PMID- 29601462
TI  - Incident Reporting to Improve Patient Safety: The Effects of Process Variance on
      Pediatric Patient Safety in the Emergency Department.
AB  - OBJECTIVE: Medical errors threaten patient safety, especially in the pediatric
      emergency department (ED) where overcrowding, multiple handoffs, and workflow
      interruptions are common. Errors related to process variance involve situations
      that are not consistent with standard ED operations or routine patient care.
      SETTING/PARTICIPANTS: We performed a planned subanalysis of the Pediatric
      Emergency Care Applied Research Network incident reporting data classified as
      process variance events. Confidential deidentified incident reports (IRs) were
      collected and classified by 2 independent investigators. Events categorized as
      process variance were then subtyped for severity and contributing factors. Data
      were analyzed using descriptive statistics. OUTCOME MEASURES: The study intention
      was to describe and measure reported medical errors related to process variance
      in 17 EDs in the Pediatric Emergency Care Applied Research Network from 2007 to
      2008. RESULTS: Between July 2007 and June 2008, 2906 eligible reports were
      reviewed. Process variance events were identified in 15.4% (447/2906). The
      majority were related to patient flow (35.4%), handoff communication (17.2%), and
      patient identification errors (15.9%). Most staff involved included nurses
      (47.9%) and physicians (28%); trainees were infrequently reported. The majority
      of events did not result in harm (65.7%); 17.9% (80/447) of cases were classified
      as unsafe conditions but did not reach the patient. Temporary harm requiring
      further treatment or hospitalization was reported in 5.6% (25/447). No events
      resulted in permanent harm, near death, or death. Contributing factors included
      human factors (92.1%), in particular handoff communication, interpersonal skills,
      and compliance with established procedures, and system-level errors (18.1%),
      including unclear or unavailable policies and inadequate staffing levels.
      CONCLUSIONS: Although process variance events accounted for approximately 1 in 6
      reported safety events, very few led to patient harm. Because human and system
      level factors contributed to most of these events, our data provide an insight
      into potential areas for further investigation and improvements to mitigate
      errors in the ED setting.

PMID- 29601464
TI  - Conjugated Hyperbilirubinemia in the Neonate and Young Infant.

PMID- 29601463
TI  - Conjugated Hyperbilirubinemia in the Neonate and Young Infant.
AB  - Cholestatic jaundice in the first few weeks of life may herald potentially life
      threatening pathology. It is therefore incumbent upon the pediatric practitioner
      to have a high index of suspicion for severe disease when investigating jaundice
      in a young infant. This article outlines the epidemiology, pathophysiology,
      differential diagnosis, and diagnostic workup for both the most common and the
      most severe causes of cholestasis in the neonatal period.

PMID- 29601465
TI  - Pediatric Emergency Medicine Fellowship Programs.

PMID- 29601466
TI  - Longitudinal Clival Fracture in a Child: Case Report and Review of the
      Literature.
AB  - Clival fracture is a rare and serious injury, which mostly results in the death
      of the victim before reaching the hospital. The entity is hardly diagnosed in the
      early phase because of high mortality rates and deficiencies in completion of
      radiological imaging. The incidence of diagnoses increased year by year after the
      usage of computed tomography gained widespread availability. In this article, we
      aimed to present radiological and clinical characteristics of a 5-year-old
      patient brought to the emergency department after a motor vehicle accident. The
      most current recommendations with regard to the management of clival fracture of
      a pediatric patient are also discussed.

PMID- 29601467
TI  - Posttraumatic High-Flow Nonischemic Priapism.
AB  - Priapism is an uncommon disorder, and nonischemic priapism is seen less
      frequently in children, generally after trauma. Although it seems to be an
      advantage that urgent intervention is not required because of no cavernous
      ischemia, it is likely to be misdiagnosed because of the asymptomatic potential.
      We aimed to present a case of posttraumatic nonischemic priapism.

PMID- 29601468
TI  - The Use of Picture Cards to Elicit Postgraduate Dental Student Feedback.
AB  - The aim of this study was to elicit information about the use of picture cards to
      stimulate student feedback following a postgraduate dental course. Twenty-nine
      general dental practitioners (GDPs) volunteered for the study. Following an
      explanation of how this style of feedback worked, students were asked to choose a
      picture card from those available and use that image to stimulate their feedback.
      An independent interviewer introduced the topic and gathered comments in the form
      of qualitative data, generated by pre-formed questions. 93% (n = 26)
      questionnaires were completed and returned. 77% (n = 20) GDPs reported enjoying
      giving their feedback by 'picture card' technique; 83% (n = 20) reported this
      form of feedback stimulated their thoughts. Qualitative data were analysed
      thematically. Some GDPs felt the picture cards helped them formulate their
      feedback, others felt being able to give feedback to a third party they did not
      know was beneficial and giving feedback as a group was helpful. This novel
      approach of using picture cards to stimulate feedback was well received by these
      GDPs. A mixed result as to the value of this style of feedback was evident. A
      group feedback session facilitated by a stranger was considered to be a valuable
      approach to take.

PMID- 29601470
TI  - Influence of Intestinal Microbiota Transplantation and NleH Expression on
      Citrobacter rodentium Colonization of Mice.
AB  - The intestinal microbiota plays an important role in regulating host resistance
      to enteric pathogens. The relative abundance of the microbiota is dependent upon
      both genetic and environmental factors. The attaching and effacing pathogens
      enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter
      rodentium cause diarrheal disease and translocate type III secretion system
      effector proteins into host cells to inhibit pro-inflammatory host responses.
      Here we determined the influence of both the intestinal microbiota and the
      expression of the C. rodentium NleH effector on C. rodentium colonization in
      different mouse models. We performed fecal transplantation experiments between
      C57BL/6J and C57BL/10ScNJ mice and found that such microbiota transfers altered
      both the host resistance to C. rodentium infection as well as the benefit or
      detriment of expressing NleH to C. rodentium intestinal colonization.

PMID- 29601471
TI  - Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1
      Mouse Breast Cancer: A Review.
AB  - Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several
      different animal models. NPS induces protective, vaccine-like effects after
      ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some
      general concepts of NPS in the context of studies with mouse metastatic 4T1
      mammary cancer showing that the postablation, vaccine-like effect is initiated by
      dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by
      inducing immunogenic, caspase-independent programmed cell death (PCD). With lower
      electric fields, like those peripheral to the primary treatment zone, NPS can
      activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads
      to increases in memory effector and central memory T-lymphocytes in the blood and
      spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment
      and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal
      effect and largely prevents spontaneous metastases to distant organs. NPS with
      fast rise-fall times and pulse durations near the plasma membrane charging time
      constant, which exhibits transient, high-frequency components (1/time = Hz),
      induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such
      effects may be responsible for release of danger-associated molecular patterns,
      including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc
      cells to induce immunogenic cell death (ICD). This likely leads to immunity and
      the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy
      providing distinct therapeutic advantages showing possible clinical utility for
      breast cancers as well as for other malignancies.

PMID- 29601469
TI  - Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental
      Sources: Potential Public Health Implications.
AB  - Due to the increased demand of animal protein in developing countries, intensive
      farming is instigated, which results in antibiotic residues in animal-derived
      products, and eventually, antibiotic resistance. Antibiotic resistance is of
      great public health concern because the antibiotic-resistant bacteria associated
      with the animals may be pathogenic to humans, easily transmitted to humans via
      food chains, and widely disseminated in the environment via animal wastes. These
      may cause complicated, untreatable, and prolonged infections in humans, leading
      to higher healthcare cost and sometimes death. In the said countries, antibiotic
      resistance is so complex and difficult, due to irrational use of antibiotics both
      in the clinical and agriculture settings, low socioeconomic status, poor
      sanitation and hygienic status, as well as that zoonotic bacterial pathogens are
      not regularly cultured, and their resistance to commonly used antibiotics are
      scarcely investigated (poor surveillance systems). The challenges that follow are
      of local, national, regional, and international dimensions, as there are no
      geographic boundaries to impede the spread of antibiotic resistance. In addition,
      the information assembled in this study through a thorough review of published
      findings, emphasized the presence of antibiotics in animal-derived products and
      the phenomenon of multidrug resistance in environmental samples. This therefore
      calls for strengthening of regulations that direct antibiotic manufacture,
      distribution, dispensing, and prescription, hence fostering antibiotic
      stewardship. Joint collaboration across the world with international bodies is
      needed to assist the developing countries to implement good surveillance of
      antibiotic use and antibiotic resistance.

PMID- 29601472
TI  - Association between Short-Term Exposure to Air Pollution and Dyslipidemias among
      Type 2 Diabetic Patients in Northwest China: A Population-Based Study.
AB  - Air pollution exposure may play an adverse role in diabetes. However, little data
      are available directly evaluating the effects of air pollution exposure in blood
      lipids of which dysfunction has been linked to diabetes or its complications. We
      aimed to evaluate the association between air pollution and lipids level among
      type 2 diabetic patients in Northwest China. We performed a population-based
      study of 3912 type 2 diabetes patients in an ongoing cohort study in China. Both
      spline and multiple linear regressions analysis were used to examine the
      association between short-term exposure to PM10, SO2, NO2 and total cholesterol
      (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high
      density lipoprotein cholesterol (HDL-C). By spline analyses, we observed that the
      relationship between SO2 and HDL-C and LDL-C was shown to be non-linear (p_non
      lin-association = 0.0162 and 0.000). An inverted U-shaped non-linear relationship
      between NO2 and LDL-C was found (p_non-lin-association < 0.0001). A J-shaped non
      linear relationship between PM10 and TC, HDL-C (p_non-lin-association = 0.0173,
      0.0367) was also revealed. In linear regression analyses, a 10 MUg/m3 increment
      in SO2 was associated with 1.31% (95% CI: 0.40-2.12%), 3.52% (95% CI: 1.07-6.03%)
      and 7.53% (95% CI: 5.98-9.09%) increase in TC, TG and LDL-C, respectively. A 10
      MUg/m3 increment in PM10 was associated with 0.45% (95% CI: 0.08-0.82%), 0.29%
      (95% CI: 0.10-0.49%) and 0.83% (95% CI: 0.21-1.45%) increase in TC, HDL-C and LDL
      C, respectively. For NO2, an increment of 10 MUg/m3 was statistically associated
      with -3.55% (95% CI: -6.40-0.61%) and 39.01% (95% CI: 31.43-47.03%) increase in
      HDL-C and LDL-C. The adverse effects of air pollutants on lipid levels were
      greater in female and elder people. Further, we found SO2 and NO2 played a more
      evident role in lipid levels in warm season, while PM10 appeared stronger in cold
      season. The findings suggest that exposure to air pollution has adverse effects
      on lipid levels among type 2 diabetes patients, and vulnerable people may pay
      more attention on severe air pollution days.

PMID- 29601473
TI  - Honey Bee Antiviral Immune Barriers as Affected by Multiple Stress Factors: A
      Novel Paradigm to Interpret Colony Health Decline and Collapse.
AB  - Any attempt to outline a logical framework in which to interpret the honey bee
      health decline and its contribution to elevated colony losses should recognize
      the importance of the multifactorial nature of the responsible syndrome and
      provide a functional model as a basis for defining and testing working
      hypotheses. We propose that covert infections by deformed wing virus (DWV)
      represent a sword of Damocles permanently threatening the survival of honey bee
      colonies and suggest that any factor affecting the honey bee&rsquo;s antiviral
      defenses can turn this pathogen into a killer. Here we discuss the available
      experimental evidence in the framework of a model based on honey bee immune
      competence as affected by multiple stress factors that is proposed as a
      conceptual tool for analyzing bee mortality and its underlying mechanisms.

PMID- 29601475
TI  - Effects of Drought on Nutrient Uptake and the Levels of Nutrient-Uptake Proteins
      in Roots of Drought-Sensitive and -Tolerant Grasses.
AB  - Climate change will increase drought in many regions of the world. Besides
      decreasing productivity, drought also decreases the concentration (%) of nitrogen
      (N) and phosphorous (P) in plants. We investigated if decreases in nutrient
      status during drought are correlated with decreases in levels of nutrient-uptake
      proteins in roots, which has not been quantified. Drought-sensitive (Hordeum
      vulgare, Zea mays) and -tolerant grasses (Andropogon gerardii) were harvested at
      mid and late drought, when we measured biomass, plant %N and P, root N- and P
      uptake rates, and concentrations of major nutrient-uptake proteins in roots (NRT1
      for NO3, AMT1 for NH4, and PHT1 for P). Drought reduced %N and P, indicating that
      it reduced nutrient acquisition more than growth. Decreases in P uptake with
      drought were correlated with decreases in both concentration and activity of P
      uptake proteins, but decreases in N uptake were weakly correlated with levels of
      N-uptake proteins. Nutrient-uptake proteins per gram root decreased despite
      increases per gram total protein, because of the larger decreases in total
      protein per gram. Thus, drought-related decreases in nutrient concentration,
      especially %P, were likely caused, at least partly, by decreases in the
      concentration of root nutrient-uptake proteins in both drought-sensitive and 
      tolerant species.

PMID- 29601474
TI  - LGR5 and BMI1 Increase Pig Intestinal Epithelial Cell Proliferation by
      Stimulating WNT/beta-Catenin Signaling.
AB  - Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and B-cell
      specific Moloney murine leukemia virus insertion site 1 (BMI1) are markers of
      fast-cycling and quiescent intestinal stem cells, respectively. To determine the
      functions of these proteins in large animals, we investigated their effects on
      the proliferation of intestinal epithelial cells from pigs. Our results indicated
      that LGR5 and BMI1 are highly conserved proteins and that the pig proteins have
      greater homology with the human proteins than do mouse proteins. Overexpression
      of either LGR5 or BMI1 promoted cell proliferation and WNT/beta-catenin signaling
      in pig intestinal epithelial cells (IPEC-J2). Moreover, the activation of
      WNT/beta-catenin signaling by recombinant human WNT3A protein increased cell
      proliferation and LGR5 and BMI1 protein levels. Conversely, inhibition of
      WNT/beta-catenin signaling using XAV939 reduced cell proliferation and LGR5 and
      BMI1 protein levels. This is the first report that LGR5 and BMI1 can increase
      proliferation of pig intestinal epithelial cells by activating WNT/beta-catenin
      signaling.

PMID- 29601476
TI  - Allelic RNA Motifs in Regulating Systemic Trafficking of Potato Spindle Tuber
      Viroid.
AB  - Intercellular RNA trafficking has been shown as a widely-existing phenomenon that
      has significant functions in many aspects of biology. Viroids, circular noncoding
      RNAs that cause plant diseases, have been a model to dissect the role of RNA
      structural motifs in regulating intercellular RNA trafficking in plants. Recent
      studies on potato spindle tuber viroid (PSTVd) showed that the RNA motif loop 19
      is important for PSTVd to spread from palisade to spongy mesophyll in infected
      leaves. Here, we performed saturated mutational analysis to uncover all possible
      functional variants of loop 19 and exploit this data to pinpoint to a three
      dimensional structural model of this motif. Interestingly, we found that two
      distinct structural motifs can replace loop 19 and retain the systemic
      trafficking capacity. One of the alternative structures rapidly emerged from the
      inoculation using a loop 19 abolished mutant that is not capable of systemic
      trafficking. Our observation indicates the flexibility of multiple structural
      arrangements interchangeably exerting similar function at a particular RNA locus.
      Taken together, this study deepens the understanding of RNA structural motifs
      regulated viroid RNA trafficking, which has broad implications for studying RNA
      intercellular trafficking as well.

PMID- 29601478
TI  - Did Harvey Learn from Katrina? Initial Observations of the Response to Companion
      Animals during Hurricane Harvey.
AB  - The aftermath of Hurricane Katrina in 2005 became the genesis of animal emergency
      management and created significant reforms in the US particularly the passage of
      the Pets Emergency and Transportation Standards Act in 2006 that required state
      and local emergency management arrangements to be pet- and service animal
      inclusive. More than a decade later Hurricane Harvey struck the Gulf states with
      all 68 directly related deaths occurring in the state of Texas. In this study,
      six key officials involved in the response underwent a semi-structured interview
      to investigate the impact of the PETS Act on preparedness and response. Though
      the results have limitations due to the low sample size, it was found that the
      PETS Act and the lessons of Hurricane Katrina had contributed to a positive
      cultural shift to including pets (companion animals) in emergency response.
      However, there was a general theme that plans required under the PETS Act were
      under-developed and many of the animal response lessons from previous emergencies
      remain unresolved. The study also observed the first empirical case of disaster
      hoarding which highlights the need for animal law enforcement agencies to be
      active in emergency response.

PMID- 29601477
TI  - Acupuncture as Add-On Treatment of the Positive, Negative, and Cognitive Symptoms
      of Patients with Schizophrenia: A Systematic Review.
AB  - Background: Schizophrenia is a severe psychiatric disorder that has a large
      impact on patients' lives. In addition to Western medicine, the use of additional
      treatments, such as acupuncture, in treating the positive, negative, and
      cognitive symptoms is increasing. Methods: We conducted a systematic review on
      the use of acupuncture as an add-on treatment for patients with schizophrenia
      that are in regular care, with a special focus on the treatment of the often
      accompanying sleep disorders. In this study, we searched the Medline,
      ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date
      of 31 December 2017, thereby following the guidelines of the Preferred Reporting
      Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our
      search resulted in 26 eligible studies with 1181 patients with schizophrenia who
      received acupuncture treatment. Most studies showed limited evidence for the use
      of acupuncture as add-on therapy in the treatment of the positive, negative, and
      cognitive symptoms, but beneficial effects have been reported in the treatment of
      the accompanying sleep disorders. Conclusions: Limited evidence was found for the
      use of acupuncture as add-on therapy in the treatment of patients with
      schizophrenia; however, positive results were found in the treatment of sleep
      disorders, but this result needs to be confirmed in large, randomized, controlled
      trials.

PMID- 29601479
TI  - Burden and Risk Factors for Cold-Related Illness and Death in New York City.
AB  - Exposure to cold weather can cause cold-related illness and death, which are
      preventable. To understand the current burden, risk factors, and circumstances of
      exposure for illness and death directly attributed to cold, we examined hospital
      discharge, death certificate, and medical examiner data during the cold season
      from 2005 to 2014 in New York City (NYC), the largest city in the United States.
      On average each year, there were 180 treat-and-release emergency department
      visits (average annual rate of 21.6 per million) and 240 hospital admissions
      (29.6 per million) for cold-related illness, and 15 cold-related deaths (1.8 per
      million). Seventy-five percent of decedents were exposed outdoors. About half of
      those exposed outdoors were homeless or suspected to be homeless. Of the 25% of
      decedents exposed indoors, none had home heat and nearly all were living in
      single-family or row homes. The majority of deaths and illnesses occurred outside
      of periods of extreme cold. Unsheltered homeless individuals, people who use
      substances and become incapacitated outdoors, and older adults with medical and
      psychiatric conditions without home heat are most at risk. This information can
      inform public health prevention strategies and interventions.

PMID- 29601480
TI  - On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity.
AB  - Tissue adhesives based on polyamidoamine (PAMAM) dendrimer, grafted with UV
      sensitive aryldiazirine (PAMAM-g-diazirine) are promising new candidates for
      light active adhesion on soft tissues. Diazirine carbene precursors form
      interfacial and intermolecular covalent crosslinks with tissues after UV light
      activation that requires no premixing or inclusion of free radical initiators.
      However, primary amines on the PAMAM dendrimer surface present a potential risk
      due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations
      with cationic pendant amines converted into neutral amide groups were evaluated.
      In vitro toxicity is reduced by an order of magnitude upon amine capping while
      retaining bioadhesive properties. The in vivo immunological response to PAMAM-g
      diazirine formulations was found to be optimal in comparison to standard
      poly(lactic-co-glycolic acid) (PLGA) thin films.

PMID- 29601481
TI  - A Co-Precursor Approach Coupled with a Supercritical Modification Method for
      Constructing Highly Transparent and Superhydrophobic Polymethylsilsesquioxane
      Aerogels.
AB  - Polymethylsilsesquioxane (PMSQ) aerogels obtained from methyltrimethoxysilane
      (MTMS) are well-known high-performance porous materials. Highly transparent and
      hydrophobic PMSQ aerogel would play an important role in transparent vacuum
      insulation panels. Herein, the co-precursor approach and supercritical
      modification method were developed to prepare the PMSQ aerogels with high
      transparency and superhydrophobicity. Firstly, benefiting from the introduction
      of tetramethoxysilane (TMOS) in the precursor, the pore structure became more
      uniform and the particle size was decreased. As the TMOS content increased, the
      light transmittance increased gradually from 54.0% to 81.2%, whereas the contact
      angle of water droplet decreased from 141 degrees  to 99.9 degrees , ascribed to
      the increase of hydroxyl groups on the skeleton surface. Hence, the supercritical
      modification method utilizing hexamethyldisilazane was also introduced to enhance
      the hydrophobic methyl groups on the aerogel's surface. As a result, the obtained
      aerogels revealed superhydrophobicity with a contact angle of 155 degrees .
      Meanwhile, the developed surface modification method did not lead to any
      significant changes in the pore structure resulting in the superhydrophobic
      aerogel with a high transparency of 77.2%. The proposed co-precursor approach and
      supercritical modification method provide a new horizon in the fabrication of
      highly transparent and superhydrophobic PMSQ aerogels.

PMID- 29601482
TI  - Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell
      Glycolysis, Growth and Motility.
AB  - Medulloblastoma is the most common malignant paediatric brain tumour and current
      therapies often leave patients with severe neurological disabilities. Four major
      molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and
      Group 4), which include additional, recently defined subgroups with different
      prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA) is a key
      enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly
      observed in cancers, associated with tumour progression and metastasis. Studies
      indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored
      as a therapeutic target for medulloblastoma. LDHA expression was examined in
      medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by
      oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and
      proliferation were examined. LDHA was significantly overexpressed in Group 3 and
      Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate
      significantly attenuated glycolysis, proliferation and motility in
      medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic
      glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH
      inhibition (LDHA, B, and C) may be more appropriate than LDHA inhibition alone.

PMID- 29601484
TI  - Optical Biosensors Based on Photonic Crystals Supporting Bound States in the
      Continuum.
AB  - A novel optical label-free bio-sensing platform based on a new class of
      resonances supported in a photonic crystal metasurface is reported herein.
      Molecular binding is detected as a shift in the resonant wavelength of the bound
      states in the continuum of radiation modes. The new configuration is applied to
      the recognition of the interaction between protein p53 and its protein regulatory
      partner murine double minute 2 (MDM2). A detection limit of 66 nM for the protein
      p53 is found. The device provides an excellent interrogation stability and loss
      free operation, requires minimal optical interrogation equipment and can be
      easily optimized to work in a wide wavelength range.

PMID- 29601483
TI  - Invertebrate Iridoviruses: A Glance over the Last Decade.
AB  - Members of the family Iridoviridae (iridovirids) are large dsDNA viruses that
      infect both invertebrate and vertebrate ectotherms and whose symptoms range in
      severity from minor reductions in host fitness to systemic disease and large
      scale mortality. Several characteristics have been useful for classifying
      iridoviruses; however, novel strains are continuously being discovered and, in
      many cases, reliable classification has been challenging. Further impeding
      classification, invertebrate iridoviruses (IIVs) can occasionally infect
      vertebrates; thus, host range is often not a useful criterion for classification.
      In this review, we discuss the current classification of iridovirids, focusing on
      genomic and structural features that distinguish vertebrate and invertebrate
      iridovirids and viral factors linked to host interactions in IIV6 (Invertebrate
      iridescent virus 6). In addition, we show for the first time how complete genome
      sequences of viral isolates can be leveraged to improve classification of new
      iridovirid isolates and resolve ambiguous relations. Improved classification of
      the iridoviruses may facilitate the identification of genus-specific virulence
      factors linked with diverse host phenotypes and host interactions.

PMID- 29601485
TI  - Biopsychosocial Assessment of Pain with Thermal Imaging of Emotional Facial
      Expression in Breast Cancer Survivors.
AB  - Background: Recent research has evaluated psychological and biological
      characteristics associated with pain in survivors of breast cancer (BC). Few
      studies consider their relationship with inflammatory activity. Voluntary facial
      expressions modify the autonomic activity and this may be useful in the hospital
      environment for clinical biopsychosocial assessment of pain. Methods: This
      research compared a BC survivors group under integral treatment (Oncology,
      Psychology, Nutrition) with a control group to assess the intensity of pain,
      behavioral interference, anxiety, depression, temperament-expression, anger
      control, social isolation, emotional regulation, and alexithymia and inflammatory
      activity, with salivary interleukin 6 (IL-6). Then, a psychophysiological
      evaluation through repeated measures of facial infrared thermal imaging (IRT) and
      hands in baseline-positive facial expression (joy)-negative facial expression
      (pain)-relaxation (diaphragmatic breathing). Results: The results showed changes
      in the IRT (p < 0.05) during the execution of facial expressions in the chin,
      perinasal, periorbital, frontal, nose, and fingers areas in both groups. No
      differences were found in the IL-6 level among the aforementioned groups, but an
      association with baseline nasal temperature (p < 0.001) was observable. The BC
      group had higher alexithymia score (p < 0.01) but lower social isolation (p <
      0.05), in comparison to the control group. Conclusions: In the low- and medium
      concentration groups of IL-6, the psychophysiological intervention proposed in
      this study has a greater effect than on the high concentration group of IL-6.
      This will be considered in the design of psychological and psychosocial
      interventions for the treatment of pain.

PMID- 29601486
TI  - In Situ-Based Gels for Nose to Brain Delivery for the Treatment of Neurological
      Diseases.
AB  - In situ-based gel drug delivery systems that can bypass the blood-brain barrier,
      deliver the therapeutics to the desired site, reduce peripheral toxicity and
      control drug release kinetics have been developed. Some of the therapeutics used
      to treat neurological diseases suffer from poor bioavailability. Preclinical
      reports from several researchers have proven that the delivery of drugs to the
      brain via the nose-to-brain route using in situ gels holds great promise.
      However, safety issues on the toxicity of the nasal mucosa, transportation of the
      drugs to specific brain regions and determination of the required dose are
      factors that must be considered when designing these gels. This review will be
      focused on in situ-based gels that are used for the delivery of therapeutics via
      the nose-to-brain route, preclinical reports and challenges.

PMID- 29601487
TI  - Gene-Therapeutic Strategies Targeting Angiogenesis in Peripheral Artery Disease.
AB  - The World Health Organization announced that cardiovascular disease is the number
      one cause of death globally, representing 31% of all global deaths. Coronary
      artery disease (CAD) affects approximately 5% of the US population aged 40 years
      and older. With an age-adjusted prevalence of approximately 12%, peripheral
      artery disease (PAD) affects at least 8 to 12 million Americans. Both CAD and PAD
      are caused by mainly atherosclerosis, the hardening and narrowing of arteries
      over the years by lipid deposition in the vascular bed. Despite the significant
      advances in interventions for revascularization and intensive medical care,
      patients with CAD or PAD who undergo percutaneous transluminal angioplasty have a
      persistent high rate of myocardial infarction, amputation, and death. Therefore,
      new therapeutic strategies are urgently needed for these patients. To overcome
      this unmet need, therapeutic angiogenesis using angiogenic growth factors has
      evolved in an attempt to stimulate the growth of new vasculature to compensate
      for tissue ischemia. After nearly 20 years of investigation, there is growing
      evidence of successful or unsuccessful gene therapy for ischemic heart and limb
      disease. This review will discuss basic and clinical data of therapeutic
      angiogenesis studies employing angiogenic growth factors for PAD patients and
      will draw conclusions on the basis of our current understanding of the biological
      processes of new vascularization.

PMID- 29601488
TI  - A Comparison of the Satiety Effects of a Fruit Smoothie, Its Fresh Fruit
      Equivalent and Other Drinks.
AB  - Energy-containing liquids are claimed to have relatively low satiating power,
      although energy in liquids is not without effect on appetite. Using the preload
      test-meal method, effects on fullness and energy intake compensation were
      compared across four drinks (water, blackcurrant squash, milk and fruit smoothie)
      and the fresh fruit equivalent of the smoothie. Preload volumes were similar, and
      the energy value of each preload was 569 kJ, except for water (0 kJ). Healthy,
      adult participants rated the preloads for liking, enjoyment, satisfaction,
      familiarity and how 'food-like' they seemed. The preload to test-meal interval
      was 2 min (n = 23) or 2 h (n = 24). The effects of the preloads on fullness
      varied with food-likeness and the rate at which they were consumed. In contrast,
      energy intake compensation versus water did not differ between the energy
      containing preloads, although it decreased over time (from 82% at 2 min to 12% at
      2 h). In conclusion, although fullness increased with food-likeness, subsequent
      energy intake compensation did not differ for energy/nutrients consumed in drinks
      compared with a food. The results also support the proposal that food intake is
      influenced predominantly by the immediate, but rapidly waning, post-ingestive
      effects of the previous 'meal' (rather than by changes in energy balance).

PMID- 29601489
TI  - The Relationship between Sleep Time and Mental Health Problems According to the
      Strengths and Difficulties Questionnaire in Children after an Earthquake
      Disaster: The Fukushima Health Management Survey.
AB  - A cross-sectional study was performed on the adverse effects of sleep time on the
      mental health of children after the Great East Japan Earthquake and subsequent
      nuclear reactor accident in March 2011. The target participants were children
      aged 4-15 years living inside the government-designated evacuation zone as of 11
      March 2011 (n = 29,585). The participants' parents/guardians completed the
      Strengths and Difficulties Questionnaire (SDQ) and sleep time data were obtained
      from the 2011 Fukushima Health Management Survey. A total of 18,745 valid
      responses were returned. We excluded questionnaires with incomplete answers
      leaving 13,272 responses for the final analysis. First, we divided the children
      into three age groups for analysis. Second, we divided each age group into four
      or five groups based on sleep time per day. We used SDQ scores >=16 to indicate a
      high risk of mental health problems. In the 4-6-year-old group, those with a
      sleep time of <9 h had a higher risk. In the 7-12-year-old group, those with >=10
      h of sleep time had a higher risk. In the 13-15-year-old group, those with >=9 h
      of sleep time had a higher risk. Shorter sleep time was associated with a higher
      risk of mental health in 4-6-year-olds. On the other hand, oversleeping was
      associated with a high risk of mental health in 7-15-year-olds.

PMID- 29601490
TI  - Synthesis of Pt-Pd Bimetallic Porous Nanostructures as Electrocatalysts for the
      Methanol Oxidation Reaction.
AB  - Pt-based bimetallic nanostructures have attracted a great deal of attention due
      to their unique nanostructures and excellent catalytic properties. In this study,
      we prepared porous Pt-Pd nanoparticles using an efficient, one-pot co-reduction
      process without using any templates or toxic reactants. In this process, Pt-Pd
      nanoparticles with different nanostructures were obtained by adjusting the
      temperature and ratio of the two precursors; and their catalytic properties for
      the oxidation of methanol were studied. The porous Pt-Pd nanostructures showed
      better electrocatalytic activity for the oxidation of methanol with a higher
      current density (0.67 mA/cm2), compared with the commercial Pt/C catalyst (0.31
      mA/cm2). This method provides one easy pathway to economically prepare different
      alloy nanostructures for various applications.

PMID- 29601491
TI  - Whole-Genome Comparison Reveals Heterogeneous Divergence and Mutation Hotspots in
      Chloroplast Genome of Eucommia ulmoides Oliver.
AB  - Eucommia ulmoides (E. ulmoides), the sole species of Eucommiaceae with high
      importance of medicinal and industrial values, is a Tertiary relic plant that is
      endemic to China. However, the population genetics study of E. ulmoides lags far
      behind largely due to the scarcity of genomic data. In this study, one complete
      chloroplast (cp) genome of E. ulmoides was generated via the genome skimming
      approach and compared to another available E. ulmoides cp genome comprehensively
      at the genome scale. We found that the structure of the cp genome in E. ulmoides
      was highly consistent with genome size variation which might result from DNA
      repeat variations in the two E. ulmoides cp genomes. Heterogeneous sequence
      divergence patterns were revealed in different regions of the E. ulmoides cp
      genomes, with most (59 out of 75) of the detected SNPs (single nucleotide
      polymorphisms) located in the gene regions, whereas most (50 out of 80) of the
      indels (insertions/deletions) were distributed in the intergenic spacers. In
      addition, we also found that all the 40 putative coding-region-located SNPs were
      synonymous mutations. A total of 71 polymorphic cpDNA fragments were further
      identified, among which 20 loci were selected as potential molecular markers for
      subsequent population genetics studies of E. ulmoides. Moreover, eight
      polymorphic cpSSR loci were also developed. The sister relationship between E.
      ulmoides and Aucuba japonica in Garryales was also confirmed based on the cp
      phylogenomic analyses. Overall, this study will shed new light on the
      conservation genomics of this endangered plant in the future.

PMID- 29601493
TI  - De-Prescribing of Psychotropic Medications in the Adult Population with
      Intellectual Disabilities: A Commentary.
AB  - The population with intellectual disabilities is one of the most vulnerable
      groups in society. Medication use is the main therapeutic intervention in this
      population and psychotropic medications can be prescribed for mental health
      conditions and for challenging behaviors. Clinical experience of prescribers and
      pharmacists working with people with intellectual disabilities suggests that
      reducing or stopping psychotropic medication is not always straightforward. What
      is required is rational, rather than rationed, prescribing of psychotropic
      medications. Concerns of clinicians working with people with intellectual
      disabilities and both formal and informal carers can result in maintenance of the
      'status quo.' Setting-related, carer-related and staff-related factors play an
      important role in the real world of people with intellectual disabilities.
      Optimizing medication regimens in the adult population with intellectual
      disabilities is complicated but it is recognized that efforts to improve the
      current state of medication utilization are required for many individuals with
      intellectual disabilities. Pharmacists have a responsibility to include the
      person and/or their carer in their efforts to promote optimization of
      psychotropic medication use in environment in which the person lives.

PMID- 29601494
TI  - The Burden of Serious Fungal Infections in Cameroon.
AB  - Fungal infections are frequent in Cameroon, and invasive fungal infections are
      sometimes detected, usually in HIV-infected patients. For these reasons, we have
      estimated the burden of fungal infections. Using published literature and
      population estimates for the at-risk group, we used deterministic modelling to
      derive national incidence and prevalence estimates for the most serious fungal
      diseases. HIV infection is common and an estimated 120,000 have CD4 counts <200 *
      106/mL and commonly present with opportunistic infection. Oesophageal candidiasis
      in HIV is common, and in poorly controlled diabetics. We estimate 6720 cases of
      cryptococcal meningitis, 9000 of Pneumocystis pneumonia, 1800 of disseminated
      histoplasmosis annually complicating AIDS, and 1200 deaths from invasive
      aspergillosis in AIDS, but there are no data. We found that 2.4% of adults have
      chronic obstructive pulmonary disease (COPD) and 2.65% have asthma, with "fungal
      asthma" affecting 20,000. Chronic pulmonary aspergillosis probably affects about
      5000 people, predominantly after tuberculosis but also with COPD and other lung
      diseases. Also, tinea capitis in schoolchildren is frequent. Overall, an
      estimated 1,235,775 people are affected by a serious fungal infection. There is
      an urgent need for government and clinician attention, improved laboratory
      facilities, fungal diagnostic tests, and competent laboratory technicians, as
      well as all World Health Organization (WHO)-endorsed essential antifungal drugs
      to be made available, as only fluconazole is registered and available in the
      country.

PMID- 29601495
TI  - A Study of Calcium-Silicate-Hydrate/Polymer Nanocomposites Fabricated Using the
      Layer-By-Layer Method.
AB  - Calcium-silicate-hydrate (CSH)/polymer nanocomposites were synthesized with the
      layer-by-layer (LBL) method, and their morphology and mechanical properties were
      investigated using atomic force microscopy (AFM) imaging and AFM nanoindentation.
      Different sets of polymers were used to produce CSH/polymer nanocomposites. The
      effect of different factors including dipping time, calcium to silicate ratios
      (C/S ratios) and pH on morphology was investigated. CSH/polymer nanocomposites
      made with different sets of polymers showed variation in morphologies. However,
      the Young&rsquo;s modulus did not seem to reveal significant differences between
      the nanocomposites studied here. In nanocomposites containing graphene oxide (GO)
      nanosheet, an increase in the density of CSH particles was observed on the GO
      nanosheet compared to areas away from the GO nanosheet, providing evidence for
      improved nucleation of CSH in the presence of GO nanosheets. An increase in
      roughness and a reduction in the packing density in nanocomposites containing GO
      nanosheets was observed.

PMID- 29601492
TI  - Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids.
AB  - Obesity leads to an inflammatory condition that is directly involved in the
      etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types
      of cancer. The classic inflammatory response is an acute reaction to infections
      or to tissue injuries, and it tends to move towards resolution and homeostasis.
      However, the inflammatory process that was observed in individuals affected by
      obesity and metabolic syndrome differs from the classical inflammatory response
      in certain respects. This inflammatory process manifests itself systemically and
      it is characterized by a chronic low-intensity reaction. The toll-like receptor 4
      (TLR4) signaling pathway is acknowledged as one of the main triggers of the
      obesity-induced inflammatory response. The aim of the present review is to
      describe the role that is played by the TLR4 signaling pathway in the
      inflammatory response and its modulation by saturated and omega-3 polyunsaturated
      fatty acids. Studies indicate that saturated fatty acids can induce inflammation
      by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated
      fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti
      inflammatory actions through the attenuation of the activation of the TLR4
      signaling pathway by either lipopolysaccharides or saturated fatty acids.

PMID- 29601496
TI  - PMMA-g-OEtOx Graft Copolymers: Influence of Grafting Degree and Side Chain Length
      on the Conformation in Aqueous Solution.
AB  - Depending on the degree of grafting (DG) and the side chain degree of
      polymerization (DP), graft copolymers may feature properties similar to
      statistical copolymers or to block copolymers. This issue is approached by
      studying aqueous solutions of PMMA-g-OEtOx graft copolymers comprising a
      hydrophobic poly(methyl methacrylate) (PMMA) backbone and hydrophilic oligo(2
      ethyl-2-oxazoline) (OEtOx) side chains. The graft copolymers were synthesized via
      reversible addition-fragmentation chain transfer (RAFT) copolymerization of
      methyl methacrylate (MMA) and OEtOx-methacrylate macromonomers of varying DP. All
      aqueous solutions of PMMA-g-OEtOx (9% &le; DG &le; 34%; 5 &le; side chain DP &le;
      24) revealed lower critical solution temperature behavior. The graft copolymer
      architecture significantly influenced the aggregation behavior, the conformation
      in aqueous solution and the coil to globule transition, as verified by means of
      turbidimetry, dynamic light scattering, nuclear magnetic resonance spectroscopy,
      and analytical ultracentrifugation. The aggregation behavior of graft copolymers
      with a side chain DP of 5 was significantly affected by small variations of the
      DG, occasionally forming mesoglobules above the cloud point temperature (Tcp),
      which was around human body temperature. On the other hand, PMMA-g-OEtOx with
      elongated side chains assembled into well-defined structures below the Tcp
      (apparent aggregation number (Nagg = 10)) that were able to solubilize Disperse
      Orange 3. The thermoresponsive behavior of aqueous solutions thus resembled that
      of micelles comprising a poly(2-ethyl-2-oxazoline) (PEtOx) shell (Tcp > 60
      &deg;C).

PMID- 29601497
TI  - Efforts to Improve the Seasonal Influenza Vaccine.
AB  - Influenza viruses infect approximately 20% of the global population annually,
      resulting in hundreds of thousands of deaths. While there are Food and Drug
      Administration (FDA) approved antiviral drugs for combating the disease,
      vaccination remains the best strategy for preventing infection. Due to the rapid
      mutation rate of influenza viruses, vaccine formulations need to be updated every
      year to provide adequate protection. In recent years, a great amount of effort
      has been focused on the development of a universal vaccine capable of eliciting
      broadly protective immunity. While universal influenza vaccines clearly have the
      best potential to provide long-lasting protection against influenza viruses, the
      timeline for their development, as well as the true universality of protection
      they afford, remains uncertain. In an attempt to reduce influenza disease burden
      while universal vaccines are developed and tested, many groups are working on a
      variety of strategies to improve the efficacy of the standard seasonal vaccine.
      This review will highlight the different techniques and technologies that have
      been, or are being, developed to improve the seasonal vaccination efforts against
      influenza viruses.

PMID- 29601498
TI  - Steroidal Constituents from Roots and Rhizomes of Smilacina japonica.
AB  - Four new steroidal constituents (1-4) along with two known steroidal glycosides
      (5 and 6) were isolated from the roots and rhizomes of Smilacina japonica.
      Analysis of their physicochemical properties and spectroscopic profiles
      identified the compounds as (25S)-5alpha-spirostan-9(11)-en-3beta, 17alpha-diol
      (1); (25S)-5alpha-spirostan-9(11)-en-3beta, 12beta-diol (2); (25S)-5alpha
      spirostan-9(11)-en-3beta, 17alpha-diol-3-O-beta-d-glucopyranoside (3); (25S)
      5alpha-spirostan-9(11)-en-3beta, 17alpha-diol-3-O-beta-d-glucopyranosyl-(1->2)
      [beta-d-glucopyranosyl-(1->3)]-beta-d-galactopyranoside (4); japonicoside B (5);
      and japonicoside C (6). All six compounds showed cytotoxic activity against SMMC
      7712, Bel-7402, A549, H460, and K562 human cancer cells.

PMID- 29601499
TI  - Short-Term Degradation of Bi-Component Electrospun Fibers: Qualitative and
      Quantitative Evaluations via AFM Analysis.
AB  - Electrospun polymeric fibers are currently used as 3D models for in vitro
      applications in biomedical areas, i.e., tissue engineering, cell and drug
      delivery. The high customization of the electrospinning process offers numerous
      opportunities to manipulate and control surface area, fiber diameter, and fiber
      density to evaluate the response of cells under different morphological and/or
      biochemical stimuli. The aim of this study was to investigate-via atomic force
      microscopy (AFM)-the chemical and morphological changes in bi-component
      electrospun fibers (BEFs) during the in vitro degradation process using a
      biological medium. BEFs were fabricated by electrospinning a mixture of synthetic
      polycaprolactone (PCL)-and natural polymers (gelatin) into a binary solution.
      During the hydrolytic degradation of protein, no significant remarkable effects
      were recognized in terms of fiber integrity. However, increases in surface
      roughness as well as a decrease in fiber diameter as a function of the
      degradation conditions were detected. We suggest that morphological and chemical
      changes due to the local release of gelatin positively influence cell behavior in
      culture, in terms of cell adhesion and spreading, thus working to mimic the
      native microenvironment of natural tissues.

PMID- 29601500
TI  - Novel Anisotropic Ductility of a High Strength Annealed Ti-20Zr-6.5Al-4V Alloy.
AB  - In this work, we investigate the mechanical properties of an annealed high
      strength Ti-20Zr-6.5Al-4V alloy in uniaxial tensile tests in different
      directions. The results show that the alloy exhibits obvious anisotropic
      ductility in different directions, while the tensile strength of the alloy
      remains almost unchanged. This phenomenon is closely related to alpha laths with
      similar orientations along the prior-beta grain boundaries. These alpha laths
      significantly affect the initiation and propagation of cracks when the alloy
      reaches its yield limit, thereby affecting the ductility of the alloy, such that
      it exhibits anisotropic ductility.

PMID- 29601501
TI  - Simultaneous Determination of Procainamide and N-acetylprocainamide in Rat Plasma
      by Ultra-High-Pressure Liquid Chromatography Coupled with a Diode Array Detector
      and Its Application to a Pharmacokinetic Study in Rats.
AB  - A simple, sensitive, and reliable reversed-phase, Ultra-High-Pressure Liquid
      Chromatography (UHPLC) coupled with a Diode Array Detector (DAD) method for the
      simultaneous determination of Procainamide (PA) and its major metabolite, N
      acetylprocainamide (NAPA), in rat plasma was developed and validated. A simple
      deproteinization method with methanol was applied to the rat plasma samples,
      which were analyzed using UHPLC equipped with DAD at 280 nm, and a SynergiTM 4 um
      polar, reversed-phase column using 1% acetic acid (pH 5.5) and methanol (76:24,
      v/v) as eluent in isocratic mode at a flow rate 0.2 mL/min. The method showed
      good linearity (r2 > 0.998) over the concentration range of 20-100,000 and 20
      10,000 ng/mL for PA and NAPA, respectively. Intra- and inter-day accuracies
      ranged from 97.7 to 110.9%, and precision was <10.5% for PA and 99.7 to 109.2 and
      <10.5%, respectively, for NAPA. The lower limit of quantification was 20 ng/mL
      for both compounds. This is the first report of the UHPLC-DAD bioanalytical
      method for simultaneous measurement of PA and NAPA. The most obvious advantage of
      this method over previously reported HPLC methods is that it requires small
      sample and injection volumes, with a straightforward, one-step sample
      preparation. It overcomes the limitations of previous methods, which use large
      sample volume and complex sample preparation. The devised method was successfully
      applied to the quantification of PA and NAPA after an intravenous bolus
      administration of 10 mg/kg procainamide hydrochloride to rats.

PMID- 29601502
TI  - Demographics and Psychological Factors Associated with Adiposity in Nurses.
AB  - Adiposity-based chronic disease (ABCD), overweight-Ow- or obesity-Ob-) in health
      personnel is as frequent as in the general population, even though they
      understand well the importance of maintaining a healthy weight. Thus, it is
      highly likely that certain demographic and psychological conditions,
      independently of knowledge, are contributing to develop ABCD. The aim of this
      study was to examine the association between these factors and ABCD in nurses.
      Data were collected from a cross-sectional study conducted in a tertiary level
      institute in Mexico City from 2012 to 2013. All the nurses of the institute of
      any age, shift, service area and seniority were invited to participate and 55%
      (265) accepted. We found that ABCD was present in 79.6%, and low self-esteem and
      emotional distress in 26% and 10%, respectively. Working in the night shift (p =
      0.031), labor seniority &ge;15 years (p = 0.006), having 1 or more children (p =
      0.021) and sessions of physical activity <30 min (p = 0.03) were associated with
      ABCD. Low self-esteem (OR = 2, 95% CI 1.150&ndash;3.07, p = 0.023) and emotional
      distress (OR = 4, 95% CI 1.472&ndash;13.078, p = 0.012) were associated with
      unhealthy lifestyle (less of 3 days per week and/or less of 30 min per session of
      physical activity and poor dietary habits). Therefore, strategies to prevent and
      treat ABCD must consider each context among nurses and psychological disorders
      need be identified to avoid an unhealthy lifestyle.

PMID- 29601504
TI  - Label-Free Electrochemical Immunoassay for C-Reactive Protein.
AB  - C-reactive protein (CRP) is one of the most expressed proteins in blood during
      acute phase inflammation, and its minute level increase has also been recognized
      for the clinical diagnosis of cardio vascular diseases. Unfortunately, the
      available commercial immunoassays are labour intensive, require large sample
      volumes, and have practical limitations, such as low stability and high
      production costs. Hence, we have developed a simple, cost effective, and label
      free electrochemical immunoassay for the measurement of CRP in a drop of serum
      sample using an immunosensor strip made up of a screen printed carbon electrode
      (SPE) modified with anti-CRP functionalized gold nanoparticles (AuNPs). The
      measurement relies on the decrease of the oxidation current of the redox
      indicator Fe3+/Fe2+, resulting from the immunoreaction between CRP and anti-CRP.
      Under optimal conditions, the present immunoassay measures CRP in a linear range
      from 0.4-200 nM (0.047-23.6 ug mL-1), with a detection limit of 0.15 nM (17 ng mL
      1, S/N = 3) and sensitivity of 90.7 nA nM-1, in addition to a good
      reproducibility and storage stability. The analytical applicability of the
      presented immunoassay is verified by CRP measurements in human blood serum
      samples. This work provides the basis for a low-priced, safe, and easy-to-use
      point-of-care immunosensor assay to measure CRP at clinically relevant
      concentrations.

PMID- 29601503
TI  - The Immunomodulatory Capacity of an Epstein-Barr Virus Abortive Lytic Cycle:
      Potential Contribution to Viral Tumorigenesis.
AB  - Epstein-Barr virus (EBV) is characterized by a bipartite life cycle in which
      latent and lytic stages are alternated. Latency is compatible with long-lasting
      persistency within the infected host, while lytic expression, preferentially
      found in oropharyngeal epithelial tissue, is thought to favor host-to-host viral
      dissemination. The clinical importance of EBV relates to its association with
      cancer, which we think is mainly a consequence of the latency/persistency
      mechanisms. However, studies in murine models of tumorigenesis/lymphomagenesis
      indicate that the lytic cycle also contributes to cancer formation. Indeed, EBV
      lytic expression is often observed in established cell lines and tumor biopsies.
      Within the lytic cycle EBV expresses a handful of immunomodulatory (BCRF1, BARF1,
      BNLF2A, BGLF5 & BILF1) and anti-apoptotic (BHRF1 & BALF1) proteins. In this
      review, we discuss the evidence supporting an abortive lytic cycle in which these
      lytic genes are expressed, and how the immunomodulatory mechanisms of EBV and
      related herpesviruses Kaposi Sarcoma herpesvirus (KSHV) and human cytomegalovirus
      (HCMV) result in paracrine signals that feed tumor cells. An abortive lytic cycle
      would reconcile the need of lytic expression for viral tumorigenesis without
      relaying in a complete cycle that would induce cell lysis to release the newly
      formed infective viral particles.

PMID- 29601505
TI  - A Community-Driven Approach to Generate Urban Policy Recommendations for Obesity
      Prevention.
AB  - There is an increasing research interest in targeting interventions at the
      neighborhood level to prevent obesity. Healthy urban environments require
      including residents' perspectives to help understanding how urban environments
      relate to residents' food choices and physical activity levels. We describe an
      innovative community-driven process aimed to develop environmental
      recommendations for obesity prevention. We conducted this study in a low-income
      area in Madrid (Spain), using a collaborative citizen science approach. First, 36
      participants of two previous Photovoice projects translated their findings into
      policy recommendations, using an adapted logical framework approach. Second, the
      research team grouped these recommendations into strategies for obesity
      prevention, using the deductive analytical strategy of successive approximation.
      Third, through a nominal group session including participants, researchers,
      public health practitioners and local policy-makers, we discussed and prioritized
      the obesity prevention recommendations. Participants identified 12 policy
      recommendations related to their food choices and 18 related to their physical
      activity. The research team grouped these into 11 concrete recommendations for
      obesity prevention. The 'top-three' ranked recommendations were: (1) to adequate
      and increase the number of public open spaces; (2) to improve the access and cost
      of existing sports facilities and (3) to reduce the cost of gluten-free and
      diabetic products.

PMID- 29601506
TI  - The Function of Personality in Suicidal Ideation from the Perspective of the
      Interpersonal-Psychological Theory of Suicide.
AB  - The Interpersonal-Psychological Theory of Suicide (IPTS) has been increasingly
      studied over the last years, responding to the demand for a valid framework
      addressing suicidality. Yet, only a few studies have explored the function of
      personality in the IPTS and none with clinical patients. We aimed to contribute
      to fill this gap in investigating the relationship between personality as
      conceptualized by the Five-Factor Model, the IPTS constructs, and a dimensional
      measure of current suicidal ideation. We conducted correlation, multiple linear
      regression, and path analyses based on a trait-interpersonal framework in a
      sample of 201 individuals visiting the psychiatric emergency room of a general
      hospital with current suicidal ideation. Neuroticism (positively) and openness
      (negatively) predicted perceived burdensomeness, while neuroticism (positively)
      and extraversion (negatively) predicted thwarted belongingness. Higher
      conscientiousness and lower extraversion were both predictors of the acquired
      capability for suicide. However, none of the models involving path analyses with
      IPTS variables as mediators of the relationship between personality traits and
      suicidal ideation was adequately adjusted to the data. Thus, it appears that
      personality plays a significant albeit modest role in suicidality when considered
      from an IPTS perspective. As personality is frequently assessed in the clinical
      routine, health professionals should consider it as complementary to detect
      individuals at risk of or presenting suicidal ideation.

PMID- 29601507
TI  - Metal (Ag/Ti)-Containing Hydrogenated Amorphous Carbon Nanocomposite Films with
      Enhanced Nanoscratch Resistance: Hybrid PECVD/PVD System and Microstructural
      Characteristics.
AB  - This study aimed to develop hydrogenated amorphous carbon thin films with
      embedded metallic nanoparticles (a-C:H:Me) of controlled size and concentration.
      Towards this end, a novel hybrid deposition system is presented that uses a
      combination of Plasma Enhanced Chemical Vapor Deposition (PECVD) and Physical
      Vapor Deposition (PVD) technologies. The a-C:H matrix was deposited through the
      acceleration of carbon ions generated through a radio-frequency (RF) plasma
      source by cracking methane, whereas metallic nanoparticles were generated and
      deposited using terminated gas condensation (TGC) technology. The resulting
      material was a hydrogenated amorphous carbon film with controlled physical
      properties and evenly dispersed metallic nanoparticles (here Ag or Ti). The
      physical, chemical, morphological and mechanical characteristics of the films
      were investigated through X-ray reflectivity (XRR), Raman spectroscopy, Scanning
      Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Transmission Electron
      Microscopy (TEM) and nanoscratch testing. The resulting amorphous carbon metal
      nanocomposite films (a-C:H:Ag and a-C:H:Ti) exhibited enhanced nanoscratch
      resistance (up to +50%) and low values of friction coefficient (<0.05),
      properties desirable for protective coatings and/or solid lubricant applications.
      The ability to form nanocomposite structures with tunable coating performance by
      potentially controlling the carbon bonding, hydrogen content, and the
      type/size/percent of metallic nanoparticles opens new avenues for a broad range
      of applications in which mechanical, physical, biological and/or combinatorial
      properties are required.

PMID- 29601508
TI  - Deep Sequencing-Based Transcriptome Profiling Reveals Avian Interferon-Stimulated
      Genes and Provides Comprehensive Insight into Newcastle Disease Virus-Induced
      Host Responses.
AB  - Newcastle disease virus (NDV) is an avian paramyxovirus that causes significant
      economic losses to the poultry industry worldwide, with variations in NDV
      pathogenicity due to the differences in virulence between strains. However, there
      is limited knowledge regarding the avian innate immune response to NDV infection.
      In this study, transcriptional profiles were obtained from chick embryo
      fibroblasts (CEFs) that were infected with the highly virulent NDV Herts/33
      strain or the nonvirulent LaSota strain using RNA-seq. This yielded 8433
      transcripts that were associated with NDV infection. This list of candidate genes
      was then further examined using Gene Ontology (GO) and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) analyses. It showed a high enrichment in the areas of
      cellular components and metabolic processes, with the cellular components
      possibly being associated with NDV pathogenicity. Among these 8433 transcripts,
      3616 transcripts associated with interferon-stimulated genes (ISGs) were
      obtained; these transcripts are involved in metabolic processes, including
      protein phosphorylation and protein modification. These results provide further
      insight into the identification of genes that are involved in NDV infection. The
      global survey of changes in gene expression performed herein provides new
      insights into the complicated molecular mechanisms underlying virus and host
      interactions and will enable the use of new strategies to protect chickens
      against this virus.

PMID- 29601509
TI  - Tactile Sliding Behavior of R2R Mass-Produced PLLA Nanosheet towards Biomedical
      Device in Skin Applications.
AB  - In this research, sliding friction was measured between the fingertip and
      nanosheet on a silicon substrate under two conditions: dry and wet. By using a
      force transducer, the tactile friction force and applied load were measured.
      According to the experimental results, the relationship of friction force and
      applied load exhibits a positive correlation under both dry and wet conditions.
      In addition, the nanosheets are able to reduce the friction force and coefficient
      of friction (COF) compared to the reference sample, especially under the wet
      condition. Under the assumption of a full contact condition, the estimated
      contact area increases with larger applied loads. Furthermore, based on the wear
      observation, the skin sliding performance caused slight abrasions to the surface
      of the nanosheet samples with a mild wear track along the sliding direction.
      Overall, the sliding behavior between the skin and nanosheet was investigated in
      terms of friction force, COF, applied load, contact area, and wear. These
      findings can contribute to the nanosheet-related research towards biomedical
      devices in skin applications.

PMID- 29601510
TI  - Design and Implementation of a Dual-Mass MEMS Gyroscope with High Shock
      Resistance.
AB  - This paper presents the design and implementation of a dual-mass MEMS gyroscope
      with high shock resistance by improving the in-phase frequency of the gyroscope
      and by using a two-stage elastic stopper mechanism and proposes a Simulink shock
      model of the gyroscope equipped with the two-stage stopper mechanism, which is a
      very efficient method to evaluate the shock resistance of the gyroscope. The
      structural design takes into account both the mechanical sensitivity and the
      shock resistance. The design of the primary structure and the analysis of the
      stopper mechanism are first introduced. Based on the expression of the restoring
      force of the stopper beam, the analytical shock response model of the gyroscope
      is obtained. By this model, the shock response of the gyroscope is theoretically
      analyzed, and the appropriate structural parameters are obtained. Then, the
      correctness of the model is verified by finite element (FE) analysis, where the
      contact collision analysis is introduced in detail. The simulation results show
      that the application of the two-stage elastic stopper mechanism can effectively
      improve the shock resistance by more than 1900 g and 1500 g in the x- and y
      directions, respectively. Finally, experimental verifications are carried out by
      using a machete hammer on the micro-gyroscope prototype fabricated by the deep
      dry silicon on glass (DDSOG) technology. The results show that the shock
      resistance of the prototype along the x-, y- and z-axes all exceed 10,000 g.
      Moreover, the output of the gyroscope can return to normal in about 2 s.

PMID- 29601511
TI  - The Height-Adaptive Parameterized Step Length Measurement Method and Experiment
      Based on Motion Parameters.
AB  - In order to tackle the inaccurate step length measurement of people with
      different heights and in different motion states, a height-adaptive method of
      step length measurement based on motion parameters is proposed in this paper.
      This method takes people's height, stride frequency, and changing accelerometer
      output while walking into integrated consideration, and builds a dynamic and
      parameterized model of their step length. In this study, these parameters were
      calibrated with thirty sets of experiment data from people with different heights
      and in different motion states, which were then verified experimentally by motion
      data of randomly selected subjects, regardless of speed and height. The
      experiment results indicate that the height-adaptive step length measurement was
      realized, thus eliminating the influence of height exerted on step length
      measurement.

PMID- 29601512
TI  - Sensor-Based Optimized Control of the Full Load Instability in Large Hydraulic
      Turbines.
AB  - Hydropower plants are of paramount importance for the integration of intermittent
      renewable energy sources in the power grid. In order to match the energy
      generated and consumed, Large hydraulic turbines have to work under off-design
      conditions, which may lead to dangerous unstable operating points involving the
      hydraulic, mechanical and electrical system. Under these conditions, the
      stability of the grid and the safety of the power plant itself can be
      compromised. For many Francis Turbines one of these critical points, that usually
      limits the maximum output power, is the full load instability. Therefore, these
      machines usually work far away from this unstable point, reducing the effective
      operating range of the unit. In order to extend the operating range of the
      machine, working closer to this point with a reasonable safety margin, it is of
      paramount importance to monitor and to control relevant parameters of the unit,
      which have to be obtained with an accurate sensor acquisition strategy. Within
      the framework of a large EU project, field tests in a large Francis Turbine
      located in Canada (rated power of 444 MW) have been performed. Many different
      sensors were used to monitor several working parameters of the unit for all its
      operating range. Particularly for these tests, more than 80 signals, including
      ten type of different sensors and several operating signals that define the
      operating point of the unit, were simultaneously acquired. The present study,
      focuses on the optimization of the acquisition strategy, which includes type,
      number, location, acquisition frequency of the sensors and corresponding signal
      analysis to detect the full load instability and to prevent the unit from
      reaching this point. A systematic approach to determine this strategy has been
      followed. It has been found that some indicators obtained with different types of
      sensors are linearly correlated with the oscillating power. The optimized
      strategy has been determined based on the correlation characteristics (linearity,
      sensitivity and reactivity), the simplicity of the installation and the
      acquisition frequency necessary. Finally, an economic and easy implementable
      protection system based on the resulting optimized acquisition strategy is
      proposed. This system, which can be used in a generic Francis turbine with a
      similar full load instability, permits one to extend the operating range of the
      unit by working close to the instability with a reasonable safety margin.

PMID- 29601513
TI  - Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen
      Peroxide Homeostasis in Wheat Seedlings.
AB  - Melatonin has emerged as a research highlight regarding its important role in
      regulating plant growth and the adaptation to the environmental stresses. In this
      study, we investigated how melatonin prevented the cadmium toxicity to wheat
      seedlings. The results demonstrated that cadmium induced the expression of
      melatonin biosynthesis-related genes and cause a significant increase of
      endogenous melatonin level. Melatonin treatment drastically alleviated the
      cadmium toxicity, resulting in increased plant height, biomass accumulation, and
      root growth. Cadmium and senescence treatment significantly increased the
      endogenous level of hydrogen peroxide, which was strictly counterbalanced by
      melatonin. Furthermore, melatonin treatment caused a significant increase of GSH
      (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The
      activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and
      superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were
      specifically improved by melatonin. Additionally, melatonin not only promoted the
      primary root growth, but also drastically enhanced the capacity of the seedling
      roots to degrade the exogenous hydrogen peroxide. These results suggested that
      melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via
      regulation of the antioxidant systems. Conclusively, this study revealed a
      crucial protective role of melatonin in the regulation of cadmium resistance in
      wheat.

PMID- 29601515
TI  - Ridge Minimization of Ablated Morphologies on ITO Thin Films Using Squared Quasi
      Flat Top Beam.
AB  - In this study, we explore the improvements in pattern quality that was obtained
      with a femtosecond laser with quasi-flat top beam profiles at the ablated edge of
      indium tin oxide (ITO) thin films for the patterning of optoelectronic devices.
      To ablate the ITO thin films, a femtosecond laser is used that has a wavelength
      and pulse duration of 1030 nm and 190 fs, respectively. The squared quasi-flat
      top beam is obtained from a circular Gaussian beam using slits with varying x-y
      axes. Then, the patterned ITO thin films are measured using both scanning
      electron and atomic force microscopes. In the case of the Gaussian beam, the
      ridge height and width are approximately 39 nm and 1.1 MUm, respectively,
      whereas, when the quasi-flat top beam is used, the ridge height and width are
      approximately 7 nm and 0.25 MUm, respectively.

PMID- 29601514
TI  - Diphenylphenoxy-Thiophene-PDI Dimers as Acceptors for OPV Applications with Open
      Circuit Voltage Approaching 1 Volt.
AB  - Two new perylenediimides (PDIs) have been developed for use as electron acceptors
      in solution-processed bulk heterojunction solar cells. The compounds were
      designed to exhibit maximal solubility in organic solvents, and reduced
      aggregation in the solid state. In order to achieve this, diphenylphenoxy groups
      were used to functionalize a monomeric PDI core, and two PDI dimers were bridged
      with either one or two thiophene units. In photovoltaic devices prepared using
      PDI dimers and a monomer in conjunction with PTB7, it was found that the
      formation of crystalline domains in either the acceptor or donor was completely
      suppressed. Atomic force microscopy, X-ray diffraction, charge carrier mobility
      measurements and recombination kinetics studies all suggest that the lack of
      crystallinity in the active layer induces a significant drop in electron
      mobility. Significant surface recombination losses associated with a lack of
      segregation in the material were also identified as a significant loss mechanism.
      Finally, the monomeric PDI was found to have sub-optimum LUMO energy matching the
      cathode contact, thus limiting charge carrier extraction. Despite these setbacks,
      all PDIs produced high open circuit voltages, reaching almost 1 V in one
      particular case.

PMID- 29601516
TI  - Identification of Requirements for Computer-Supported Matching of Food
      Consumption Data with Food Composition Data.
AB  - This paper identifies the requirements for computer-supported food matching, in
      order to address not only national and European but also international current
      related needs and represents an integrated research contribution of the FP7
      EuroDISH project. The available classification and coding systems and the
      specific problems of food matching are summarized and a new concept for food
      matching based on optimization methods and machine-based learning is proposed. To
      illustrate and test this concept, a study has been conducted in four European
      countries (i.e., Germany, The Netherlands, Italy and the UK) using different
      classification and coding systems. This real case study enabled us to evaluate
      the new food matching concept and provide further recommendations for future
      work. In the first stage of the study, we prepared subsets of food consumption
      data described and classified using different systems, that had already been
      manually matched with national food composition data. Once the food matching
      algorithm was trained using this data, testing was performed on another subset of
      food consumption data. Experts from different countries validated food matching
      between consumption and composition data by selecting best matches from the
      options given by the matching algorithm without seeing the result of the
      previously made manual match. The evaluation of study results stressed the
      importance of the role and quality of the food composition database as compared
      to the selected classification and/or coding systems and the need to continue
      compiling national food composition data as eating habits and national dishes
      still vary between countries. Although some countries managed to collect
      extensive sets of food consumption data, these cannot be easily matched with food
      composition data if either food consumption or food composition data are not
      properly classified and described using any classification and coding systems.
      The study also showed that the level of human expertise played an important role,
      at least in the training stage. Both sets of data require continuous development
      to improve their quality in dietary assessment.

PMID- 29601517
TI  - The Mechanical Properties and In Vitro Biocompatibility of PM-Fabricated Ti-28Nb
      35.4Zr Alloy for Orthopedic Implant Applications.
AB  - A biocompatible Ti-28Nb-35.4Zr alloy used as bone implant was fabricated through
      the powder metallurgy process. The effects of mechanical milling and sintering
      temperatures on the microstructure and mechanical properties were investigated
      systematically, before in vitro biocompatibility of full dense Ti-28Nb-35.4Zr
      alloy was evaluated by cytotoxicity tests. The results show that the mechanical
      milling and sintering temperatures have significantly effects on the density and
      mechanical properties of the alloys. The relative density of the alloy fabricated
      by the atomized powders at 1500  degrees C is only 83 +/- 1.8%, while the
      relative density of the alloy fabricated by the ball-milled powders can rapidly
      reach at 96.4 +/- 1.3% at 1500  degrees C. When the temperature was increased to
      1550  degrees C, the alloy fabricated by ball-milled powders achieve full density
      (relative density is 98.1 +/- 1.2%). The PM-fabricated Ti-28Nb-35.4Zr alloy by
      ball-milled powders at 1550  degrees C can achieve a wide range of mechanical
      properties, with a compressive yield strength of 1058 +/- 35.1 MPa, elastic
      modulus of 50.8 +/- 3.9 GPa, and hardness of 65.8 +/- 1.5 HRA. The in vitro
      cytotoxicity test suggests that the PM-fabricated Ti-28Nb-35.4Zr alloy by ball
      milled powders at 1550  degrees C has no adverse effects on MC3T3-E1 cells with
      cytotoxicity ranking of 0 grade, which is nearly close to ELI Ti-6Al-4V or CP Ti.
      These properties and the net-shape manufacturability makes PM-fabricated Ti-28Nb
      35.4Zr alloy a low-cost, highly-biocompatible, Ti-based biomedical alloy.

PMID- 29601519
TI  - Special Issue: Response of Microbial Communities to Environmental Changes.
AB  - Environmental issues such as eutrophication, ocean acidification, sea level rise,
      saltwater intrusion, increase in carbon dioxide levels, or rise of average global
      temperatures, among many others, are impacting and changing whole ecosystems
      [...].

PMID- 29601518
TI  - High Level Expression and Purification of the Clinically Active Antimicrobial
      Peptide P-113 in Escherichia coli.
AB  - P-113, which was originally derived from the human saliva protein histatin 5, is
      a histidine-rich antimicrobial peptide with the sequence AKRHHGYKRKFH. P-113 is
      currently undergoing phase II clinical trial as a pharmaceutical agent to fight
      against fungal infections in HIV patients with oral candidiasis. Previously, we
      developed a new procedure for the high-yield expression and purification of
      hG31P, an analogue and antagonist of human CXCL8. Moreover, we have successfully
      removed lipopolysaccharide (LPS, endotoxin) associated with hG31P in the
      expression with Escherichia coli. In this paper, we have used hG31P as a novel
      fusion protein for the expression and purification of P-113. The purity of the
      expressed P-113 is more than 95% and the yield is 4 mg P-113 per liter of E. coli
      cell culture in Luria-Bertani (LB) medium. The antimicrobial activity of the
      purified P-113 was tested. Furthermore, we used circular dichroism (CD) and
      nuclear magnetic resonance (NMR) spectroscopy to study the structural properties
      of P-113. Our results indicate that using hG31P as a fusion protein to obtain
      large quantities of P-113 is feasible and is easy to scale up for commercial
      production. An effective way of producing enough P-113 for future clinical
      studies is evident in this study.

PMID- 29601520
TI  - Ageing Study of Palm Oil and Coconut Oil in the Presence of Insulation Paper for
      Transformers Application.
AB  - This paper presents a sealed ageing study of palm oil (PO) and coconut oil (CO)
      in the presence of insulation paper. The type of PO under study is refined,
      bleached, and deodorized palm oil (RBDPO) olein. Three different variations of
      RBDPO and one sample of CO are aged at temperatures of 90  degrees C, 110 
      degrees C, and 130  degrees C. The properties of RBDPO and CO as well as paper
      under ageing are then analysed through dielectric and physicochemical
      measurements. It is found that the effect of ageing is not significant on the
      alternating current (AC) breakdown voltages and relative permittivities of RBDPO
      and CO. There is a slight increment trend of the resistivity for CO, while for
      all of the RBDPO, the resistivity slightly decreases as the ageing progresses.
      Only CO shows an apparent reduction of the dielectric dissipation factor.
      Throughout the ageing time, the acidities of all of the RBDPO and CO remain at
      low level, while the moisture in oils decreases. The tensile index (TI) of the
      papers for all of the RBDPO and CO retain more than 50% of the TI. A significant
      increment of the paper ageing rates of all of the RBDPO and CO is observed at an
      ageing temperature of 130  degrees C.

PMID- 29601522
TI  - Investigating the Mechanism behind 'Ant Nest' Corrosion on Copper Tube.
AB  - A research investigation of "ant nest" corrosion (ANC) on copper tube was
      conducted in terms of the variables of the corrosion potential and pH value in
      103 ppm copper formate solution over 20 days. The paper presents the surface and
      cross-sectional observations and examines Cu2O and H2O as the stable chemical
      species produced. A Cannizzaro reaction as a disproportionation reaction from
      formic acid and a comproportionation reaction from the metallic copper tube and
      copper formate solution critically influenced the ANC mechanism. The paper also
      categorizes the ANC attack as a rapid reaction system from the electrochemical
      point of view by using a polarization resistance curve.

PMID- 29601523
TI  - Genome-Wide Analysis of DCL, AGO, and RDR Gene Families in Pepper (Capsicum
      Annuum L.).
AB  - RNA silencing is an evolutionarily conserved mechanism that regulates variety of
      cellular processes in plants. Argonaute protein (AGO), Dicer-like protein (DCL)
      and RNA-dependent RNA polymerase (RDR) are critical components of RNA silencing.
      These efficient and indispensable components of the RNAi pathway have not been
      identified and characterized in pepper. In this study, we identified 12 CaAGO, 4
      CaDCL and 6 CaRDR genes in pepper and compared them with those of Arabidopsis,
      tobacco, potato and tomato. Detailed phylogenetic analyses revealed that each
      CaAGO, CaDCL and CaRDR protein family were classified into four clades. The
      tissue specific expression and respond to abiotic or biotic stress were studied.
      The real-time quantitative polymerase chain reaction (PCR) results demonstrated
      that CaAGO2, CaAGO10b, CaDCL2 and CaDCL4 were upregulated with cucumber mosaic
      virus (CMV), potato virus Y (PVY) and tobacco mosaic virus (TMV) infections,
      whereas they showed difference expression patterns in response to abiotic stress.
      In addition, we found that many of the candidate genes were induced by
      phytohormones and H2O2 treatment. Our results provide useful information for
      further elucidation of gene silencing pathways and RNAi-mediated host immunity in
      pepper.

PMID- 29601524
TI  - The Mental Health Status and Intellectual Ability of Unwed Mothers Dwelling in
      Korean Shelter Homes.
AB  - Although many unwed mothers have issues concerning mental health and intellectual
      ability, little research has focused on their mental and cognitive status. Due to
      the public stigma attached to unwed mothers in South Korea, they tend to conceal
      their status and are less likely to seek psychiatric and psychological help. In
      this context, this study aims to assess the current status of their mental health
      and intellectual characteristics. A total of 48 unwed mothers from two shelter
      homes in South Korea agreed to participate in the study. We compared the mental
      health status of these unwed mothers with that of the general female population.
      Unwed mothers were more likely than those of the general female population to
      have mood disorders, post traumatic stress disorder (PTSD), alcohol and nicotine
      use disorders, and attention-deficit hyperactivity disorder (ADHD). Among the 48
      unwed mothers, 20 (41.7%) had an IQ of less than 70, and the mean IQ (78.31) was
      significantly lower than the normalized mean IQ of the general female population.
      This study confirmed that unwed mothers dwelling in Korean shelter homes are more
      likely than the general female population to have mental disorders.

PMID- 29601521
TI  - Rebelling against the (Insulin) Resistance: A Review of the Proposed Insulin
      Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds.
AB  - Insulin resistance is a major risk factor for diseases such as type 2 diabetes
      and metabolic syndrome. Current methods for management of insulin resistance
      include pharmacological therapies and lifestyle modifications. Several clinical
      studies have shown that leguminous plants such as soybeans and pulses (dried
      beans, dried peas, chickpeas, lentils) are able to reduce insulin resistance and
      related type 2 diabetes parameters. However, to date, no one has summarized the
      evidence supporting a mechanism of action for soybeans and pulses that explains
      their ability to lower insulin resistance. While it is commonly assumed that the
      biological activities of soybeans and pulses are due to their antioxidant
      activities, these bioactive compounds may operate independent of their
      antioxidant properties and, thus, their ability to potentially improve insulin
      sensitivity via alternative mechanisms needs to be acknowledged. Based on
      published studies using in vivo and in vitro models representing insulin
      resistant states, the proposed mechanisms of action for insulin-sensitizing
      actions of soybeans, chickpeas, and their bioactive compounds include increasing
      glucose transporter-4 levels, inhibiting adipogenesis by down-regulating
      peroxisome proliferator-activated receptor-gamma, reducing adiposity, positively
      affecting adipokines, and increasing short-chain fatty acid-producing bacteria in
      the gut. Therefore, this review will discuss the current evidence surrounding the
      proposed mechanisms of action for soybeans and certain pulses, and their
      bioactive compounds, to effectively reduce insulin resistance.

PMID- 29601525
TI  - Discrete Indoor Three-Dimensional Localization System Based on Neural Networks
      Using Visible Light Communication.
AB  - Indoor localization estimation has become an attractive research topic due to
      growing interest in location-aware services. Many research works have proposed
      solving this problem by using wireless communication systems based on
      radiofrequency. Nevertheless, those approaches usually deliver an accuracy of up
      to two metres, since they are hindered by multipath propagation. On the other
      hand, in the last few years, the increasing use of light-emitting diodes in
      illumination systems has provided the emergence of Visible Light Communication
      technologies, in which data communication is performed by transmitting through
      the visible band of the electromagnetic spectrum. This brings a brand new
      approach to high accuracy indoor positioning because this kind of network is not
      affected by electromagnetic interferences and the received optical power is more
      stable than radio signals. Our research focus on to propose a fingerprinting
      indoor positioning estimation system based on neural networks to predict the
      device position in a 3D environment. Neural networks are an effective
      classification and predictive method. The localization system is built using a
      dataset of received signal strength coming from a grid of different points. From
      the these values, the position in Cartesian coordinates ( x , y , z ) is
      estimated. The use of three neural networks is proposed in this work, where each
      network is responsible for estimating the position by each axis. Experimental
      results indicate that the proposed system leads to substantial improvements to
      accuracy over the widely-used traditional fingerprinting methods, yielding an
      accuracy above 99% and an average error distance of 0.4 mm.

PMID- 29601526
TI  - Can Periodical Examinations of Employees Be Useful in Detection of Glycaemia
      Impairment and Improving Patients' Adherence to Medical Recommendations?
AB  - Worldwide epidemiological data indicates insufficient diagnosis of diabetes as an
      increasing public health problem. In the search for solutions to this
      disadvantageous situation, occupational medicine health services seem to open up
      a unique opportunity to recognize some abnormalities in the early stages,
      especially among the asymptomatic working-age population. 316 workers underwent
      obligatory prophylactic examinations. In patients with twice assayed FGL >= 126
      mg/dL (7.0 mmol/L) an additional intervention was implemented, including further
      diagnostic processes and therapy in General Practice (GP), followed by
      examination by an occupational health specialist within 3 months. The diagnosis
      of previously unknown diabetes was established among 2.5% of examined workers.
      All patients referred to the GP due to detected glycaemia impairment visited
      their doctor and finished the diagnostic process, took up therapy constrained by
      the occupational health physician to show the effects of intervention within 3
      months. Prophylactic medical check-ups allow improved compliance and medical
      surveillance over glycaemia impairment in patients with prediabetes states,
      unknown diabetes or uncontrolled clinical course of diabetes. Considering fasting
      glucose level during mandatory prophylactic examination helps effective
      prevention of diabetes and its complications and thus provides public health
      system benefits.

PMID- 29601527
TI  - Sequence and Haplotypes Variation of the Ovine Uncoupling Protein-1 Gene (UCP1)
      and Their Association with Growth and Carcass Traits in New Zealand Romney Lambs.
AB  - Uncoupling protein-1 gene (UCP1) plays an important role in the regulation of
      thermogenesis, energy expenditure, and protection against oxidative stress. In
      this study, six separate UCP1 regions: region-1 and region-2 (two parts of the
      promoter), region-3 and region-4 (two parts of intron 1), region-5 (spanning part
      of intron 5 and part of exon 6), and region-6 (spanning part of exon 6 and part
      of the 3'-UTR) from a variety of sheep breeds, were analysed using polymerase
      chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analyses.
      In total, 30 single nucleotide polymorphisms (SNPs) were detected. Of these, 14
      were located in the promoter, eight were found in intron 1, six were found in
      intron 5, and one was found in the 3'-UTR. One substitution in exon 6 (c.910A/G)
      would putatively result in an amino acid change (p.Thr304Ala). Twenty-eight novel
      SNPs and nine new haplotypes spanning region-2 to region-5 were identified. Of
      these nine haplotypes, five were common (B2-A5, C2-A5, C2-C5, A2-A5, and A2-B5)
      and four were rare (C2-B5, A2-C5, B2-C5, and B2-B5) in the sheep investigated. Of
      the five common haplotypes found in 314 New Zealand Romney sheep for which growth
      and carcass trait data were available, the presence of A2-B5 was associated with
      decreased hot carcass weight (HCW) and loin lean-meat yield (p = 0.006, p =
      0.032, respectively), and the presence of C2-C5 was associated with a decreased
      proportion of leg lean-meat yield (p = 0.047) in the carcasses. No associations
      were found with growth traits. These results confirm that ovine UCP1 is a
      variable gene and may have value as a genetic marker for sheep breeding.

PMID- 29601529
TI  - Assessing the Health-Care Risk: The Clinical-VaR, a Key Indicator for Sound
      Management.
AB  - Clinical risk includes any undesirable situation or operational factor that may
      have negative consequences for patient safety or capable of causing an adverse
      event (AE). The AE, intentional or unintentionally, may be related to the human
      factor, that is, medical errors (MEs). Therefore, the importance of the health
      care risk management is a current and relevant issue on the agenda of many public
      and private institutions. The objective of the management has been evolving from
      the identification of AE to the assessment of cost-effective and efficient
      measures that improve the quality control through monitoring. Consequently, the
      goal of this paper is to propose a Key Risk Indicator (KRI) that enhances the
      advancement of the health-care management system. Thus, the application of the
      Value at Risk (VaR) concept in combination to the Loss Distribution Approach
      (LDA) is proved to be a proactive tool, within the frame of balanced scorecard
      (BSC), in health organizations. For this purpose, the historical events recorded
      in the Algo-OpData(r) database (Algorithmics Inc., Toronto, ON, Canada, IBM,
      Armonk, NY, USA) have been used. The analysis highlights the importance of risk
      in the financials outcomes of the sector. The results of paper show the
      usefulness of the Clinical-VaR to identify and monitor the risk and
      sustainability of the implemented controls.

PMID- 29601528
TI  - Stem Cells Therapy for Spinal Cord Injury.
AB  - Spinal cord injury (SCI), a serious public health issue, most likely occurs in
      previously healthy young adults. Current therapeutic strategies for SCI includes
      surgical decompression and pharmacotherapy, however, there is still no gold
      standard for the treatment of this devastating condition. Inefficiency and
      adverse effects of standard therapy indicate that novel therapeutic strategies
      are required. Because of their neuroregenerative and neuroprotective properties,
      stem cells are a promising tool for the treatment of SCI. Herein, we summarize
      and discuss the promising therapeutic potential of human embryonic stem cells
      (hESC), induced pluripotent stem cells (iPSC) and ependymal stem/progenitor cells
      (epSPC) for SCI.

PMID- 29601530
TI  - MetStabOn-Online Platform for Metabolic Stability Predictions.
AB  - Metabolic stability is an important parameter to be optimized during the complex
      process of designing new active compounds. Tuning this parameter with the
      simultaneous maintenance of a desired compound's activity is not an easy task due
      to the extreme complexity of metabolic pathways in living organisms. In this
      study, the platform for in silico qualitative evaluation of metabolic stability,
      expressed as half-lifetime and clearance was developed. The platform is based on
      the application of machine learning methods and separate models for human, rat
      and mouse data were constructed. The compounds' evaluation is qualitative and two
      types of experiments can be performed-regression, which is when the compound is
      assigned to one of the metabolic stability classes (low, medium, high) on the
      basis of numerical value of the predicted half-lifetime, and classification, in
      which the molecule is directly assessed as low, medium or high stability. The
      results show that the models have good predictive power, with accuracy values
      over 0.7 for all cases, for Sequential Minimal Optimization (SMO), k-nearest
      neighbor (IBk) and Random Forest algorithms. Additionally, for each of the
      analyzed compounds, 10 of the most similar structures from the training set (in
      terms of Tanimoto metric similarity) are identified and made available for
      download as separate files for more detailed manual inspection. The predictive
      power of the models was confronted with the external dataset, containing
      metabolic stability assessment via the GUSAR software, leading to good
      consistency of results for SMOreg and Naive Bayes (~0.8 on average). The tool is
      available online.

PMID- 29601531
TI  - A Hybrid Bionic Image Sensor Achieving FOV Extension and Foveated Imaging.
AB  - Based on bionic compound eye and human foveated imaging mechanisms, a hybrid
      bionic image sensor (HBIS) is proposed in this paper to extend the field of view
      (FOV) with high resolution. First, the hybrid bionic imaging model was developed
      and the structure parameters of the HBIS were deduced. Second, the properties of
      the HBIS were simulated, including FOV extension, super-resolution imaging,
      foveal ratio and so on. Third, a prototype of the HBIS was developed to validate
      the theory. Imaging experiments were carried out, and the results are in
      accordance with the simulations, proving the potential of the HBIS for large FOV
      and high-resolution imaging with low cost.

PMID- 29601532
TI  - Eight-Channel AC Magnetosusceptometer of Magnetic Nanoparticles for High
      Throughput and Ultra-High-Sensitivity Immunoassay.
AB  - An alternating-current magnetosusceptometer of antibody-functionalized magnetic
      nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high
      sensitivity, high-critical-temperature superconducting quantum interference
      device was used in the magnetosusceptometer. Minute levels of biomarkers of early
      stage neurodegeneration diseases were detectable in serum, but measuring each
      biomarker required approximately 4 h. Hence, an eight-channel platform was
      developed in this study to fit minimal screening requirements for Alzheimer's
      disease. Two consistent results were measured for three biomarkers, namely
      Abeta40, Abeta42, and tau protein, per human specimen. This paper presents the
      instrument configuration as well as critical characteristics, such as the low
      noise level variations among channels, a high signal-to-noise ratio, and the
      coefficient of variation for the biomarkers' IMR values. The instrument's
      ultrahigh sensitivity levels for the three biomarkers and the substantially
      shorter total measurement time in comparison with the previous single- and four
      channels platforms were also demonstrated in this study. Thus, the eight-channel
      instrument may serve as a powerful tool for clinical high-throughput screening of
      Alzheimer's disease.

PMID- 29601533
TI  - Aptamer-Modified Magnetic Beads in Biosensing.
AB  - Magnetic beads (MBs) are versatile tools for the purification, detection, and
      quantitative analysis of analytes from complex matrices. The superparamagnetic
      property of magnetic beads qualifies them for various analytical applications. To
      provide specificity, MBs can be decorated with ligands like aptamers, antibodies
      and peptides. In this context, aptamers are emerging as particular promising
      ligands due to a number of advantages. Most importantly, the chemical synthesis
      of aptamers enables straightforward and controlled chemical modification with
      linker molecules and dyes. Moreover, aptamers facilitate novel sensing strategies
      based on their oligonucleotide nature that cannot be realized with conventional
      peptide-based ligands. Due to these benefits, the combination of aptamers and MBs
      was already used in various analytical applications which are summarized in this
      article.

PMID- 29601534
TI  - Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited
      therapy options and dismal prognosis. In recent years, the role of immune cells
      within the tumor microenvironment (TME) has become a major area of interest. In
      this review, we discuss the current knowledge of heterogeneity in immune cell
      content and checkpoint expression in MPM in relation to prognosis and prediction
      of treatment efficacy. Generally, immune-suppressive cells such as M2
      macrophages, myeloid-derived suppressor cells and regulatory T cells are present
      within the TME, with extensive heterogeneity in cell numbers. Infiltration of
      effector cells such as cytotoxic T cells, natural killer cells and T helper cells
      is commonly found, also with substantial patient to patient heterogeneity. PD-L1
      expression also varied greatly (16-65%). The infiltration of immune cells in
      tumor and associated stroma holds key prognostic and predictive implications. As
      such, there is a strong rationale for thoroughly mapping the TME to better target
      therapy in mesothelioma. Researchers should be aware of the extensive
      possibilities that exist for a tumor to evade the cytotoxic killing from the
      immune system. Therefore, no "one size fits all" treatment is likely to be found
      and focus should lie on the heterogeneity of the tumors and TME.

PMID- 29601535
TI  - Different Natural Selection Pressures on the atpF Gene in Evergreen
      Sclerophyllous and Deciduous Oak Species: Evidence from Comparative Analysis of
      the Complete Chloroplast Genome of Quercus aquifolioides with Other Oak Species.
AB  - Quercus is an economically important and phylogenetically complex genus in the
      family Fagaceae. Due to extensive hybridization and introgression, it is
      considered to be one of the most challenging plant taxa, both taxonomically and
      phylogenetically. Quercus aquifolioides is an evergreen sclerophyllous oak
      species that is endemic to, but widely distributed across, the Hengduanshan
      Biodiversity Hotspot in the Eastern Himalayas. Here, we compared the fully
      assembled chloroplast (cp) genome of Q. aquifolioides with those of three closely
      related species. The analysis revealed a cp genome ranging in size from 160,415
      to 161,304 bp and with a typical quadripartite structure, composed of two
      inverted repeats (IRs) separated by a small single copy (SSC) and a large single
      copy (LSC) region. The genome organization, gene number, gene order, and GC
      content of these four Quercus cp genomes are similar to those of many angiosperm
      cp genomes. We also analyzed the Q. aquifolioides repeats and microsatellites.
      Investigating the effects of selection events on shared protein-coding genes
      using the Ka/Ks ratio showed that significant positive selection had acted on the
      atpF gene of Q. aquifolioides compared to two deciduous oak species, and that
      there had been significant purifying selection on the atpF gene in the
      chloroplast of evergreen sclerophyllous oak trees. In addition, site-specific
      selection analysis identified positively selected sites in 12 genes. Phylogenetic
      analysis based on shared protein-coding genes from 14 species defined Q.
      aquifolioides as belonging to sect. Heterobalanus and being closely related to Q.
      rubra and Q. aliena. Our findings provide valuable genetic information for use in
      accurately identifying species, resolving taxonomy, and reconstructing the
      phylogeny of the genus Quercus.

PMID- 29601537
TI  - Polar Cooperative Navigation Algorithm for Multi-Unmanned Underwater Vehicles
      Considering Communication Delays.
AB  - To solve the navigation accuracy problems of multi-Unmanned Underwater Vehicles
      (multi-UUVs) in the polar region, a polar cooperative navigation algorithm for
      multi-UUVs considering communication delays is proposed in this paper. UUVs are
      important pieces of equipment in ocean engineering for marine development. For
      UUVs to complete missions, precise navigation is necessary. It is difficult for
      UUVs to establish true headings because of the rapid convergence of Earth
      meridians and the severe polar environment. Based on the polar grid navigation
      algorithm, UUV navigation in the polar region can be accomplished with the
      Strapdown Inertial Navigation System (SINS) in the grid frame. To save costs, a
      leader-follower type of system is introduced in this paper. The leader UUV helps
      the follower UUVs to achieve high navigation accuracy. Follower UUVs correct
      their own states based on the information sent by the leader UUV and the relative
      position measured by ultra-short baseline (USBL) acoustic positioning. The
      underwater acoustic communication delay is quantized by the model. In this paper,
      considering underwater acoustic communication delay, the conventional adaptive
      Kalman filter (AKF) is modified to adapt to polar cooperative navigation. The
      results demonstrate that the polar cooperative navigation algorithm for multi
      UUVs that considers communication delays can effectively navigate the sailing of
      multi-UUVs in the polar region.

PMID- 29601536
TI  - In Vitro Characteristics of Phages to Guide 'Real Life' Phage Therapy
      Suitability.
AB  - The increasing problem of antibiotic-resistant pathogens has put enormous
      pressure on healthcare providers to reduce the application of antibiotics and to
      identify alternative therapies. Phages represent such an alternative with
      significant application potential, either on their own or in combination with
      antibiotics to enhance the effectiveness of traditional therapies. However, while
      phage therapy may offer exciting therapeutic opportunities, its evaluation for
      safe and appropriate use in humans needs to be guided initially by reliable and
      appropriate assessment techniques at the laboratory level. Here, we review the
      process of phage isolation and the application of individual pathogens or
      reference collections for the development of specific or "off-the-shelf"
      preparations. Furthermore, we evaluate current characterization approaches to
      assess the in vitro therapeutic potential of a phage including its spectrum of
      activity, genome characteristics, storage and administration requirements and
      effectiveness against biofilms. Lytic characteristics and the ability to overcome
      anti-phage systems are also covered. These attributes direct phage selection for
      their ultimate application as antimicrobial agents. We also discuss current
      pitfalls in this research area and propose that priority should be given to unify
      current phage characterization approaches.

PMID- 29601538
TI  - Brain-Computer Interface Spellers: A Review.
AB  - A Brain-Computer Interface (BCI) provides a novel non-muscular communication
      method via brain signals. A BCI-speller can be considered as one of the first
      published BCI applications and has opened the gate for many advances in the
      field. Although many BCI-spellers have been developed during the last few
      decades, to our knowledge, no reviews have described the different spellers
      proposed and studied in this vital field. The presented speller systems are
      categorized according to major BCI paradigms: P300, steady-state visual evoked
      potential (SSVEP), and motor imagery (MI). Different BCI paradigms require
      specific electroencephalogram (EEG) signal features and lead to the development
      of appropriate Graphical User Interfaces (GUIs). The purpose of this review is to
      consolidate the most successful BCI-spellers published since 2010, while
      mentioning some other older systems which were built explicitly for spelling
      purposes. We aim to assist researchers and concerned individuals in the field by
      illustrating the highlights of different spellers and presenting them in one
      review. It is almost impossible to carry out an objective comparison between
      different spellers, as each has its variables, parameters, and conditions.
      However, the gathered information and the provided taxonomy about different BCI
      spellers can be helpful, as it could identify suitable systems for first-hand
      users, as well as opportunities of development and learning from previous studies
      for BCI researchers.

PMID- 29601540
TI  - Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic
      Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity.
AB  - CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be
      effective in reducing tumor size and increasing lifespan in tumor-bearing mice.
      Such capability is conferred by its cell-penetrating peptide character, which
      allows it to enter cells and elicit a pro-apoptotic effect through its major
      mediator, COMMD1 protein. Cell-penetrating peptides are able to use different
      internalization mechanisms, such as endocytosis or direct transduction through
      the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several
      non-tumor- and tumor-derived cell lines, no data regarding the relationship
      between cell line sensitivity, cell penetrating capacity, the internalization
      mechanisms involved, COMMD1 expression levels, or its subcellular localization
      has yet been produced. Here, we present the results obtained from a comparative
      analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms
      involved in three human tumor-derived cell lines from different origins: mammary
      gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell
      surface markers relevant for internalization processes such as
      phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization,
      were also evaluated. We found that both endocytosis and transduction are involved
      in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552
      incorporation efficiency and contribution of each mechanism is cell-line
      dependent. Finally, sensitivity was directly correlated with high internalization
      capacity in those cell lines where endocytosis had a major contribution on CIGB
      552 internalization.

PMID- 29601539
TI  - The Potential for Connexin Hemichannels to Drive Breast Cancer Progression
      through Regulation of the Inflammatory Response.
AB  - Over the past few decades, connexin hemichannels have become recognized as major
      players in modulating the inflammatory response. Chronic inflammation is
      documented to promote tumorigenesis and is a critical component of tumor
      progression. Furthermore, inflammation is strongly linked to angiogenesis,
      immunotolerance, invasiveness, metastasis, and resistance in breast cancers. In
      this review, the literature on the role of connexin hemichannels in inflammation
      is summarized, and the potential role for hemichannel-mediated inflammation in
      driving breast cancer progression is discussed. Lastly, the potential for
      connexin-based therapeutics to modulate the inflammatory component of the tumor
      microenvironment as an avenue for the treatment of breast cancer is also
      discussed.

PMID- 29601541
TI  - Expression Stabilities of Ten Candidate Reference Genes for RT-qPCR in
      Zanthoxylum bungeanum Maxim.
AB  - Real-time reverse transcription quantitative PCR has become a common method for
      studying gene expression, however, the optimal selection of stable reference
      genes is a prerequisite for obtaining accurate quantification of transcript
      abundance. Suitable reference genes for RT-qPCR have not yet been identified for
      Chinese prickly ash (Zanthoxylum bungeanum Maxim.). Chinese prickly ash is the
      source of an important food seasoning in China. In recent years, Chinese prickly
      ash has also been developed as a medicinal plant. The expression stabilities of
      ten genes (18S, 28S, EF, UBA, UBQ, TIF, NTB, TUA, RPS, and TIF5A) were evaluated
      in roots, stems, leaves, flowers and fruits at five developmental stages and also
      under stress from cold, drought, and salt. To do this we used three different
      statistical algorithms: geNorm, NormFinder and BestKeeper. Among the genes
      investigated, UBA and UBQ were found to be most stable for the different
      cultivars and different tissues examined, UBQ and TIF for fruit developmental
      stage. Meanwhile, EF and TUA were most stable under cold treatment, EF and UBQ
      under drought treatment and NTB and RPS under salt treatment. UBA and UBQ for all
      samples evaluated were most stably expressed, but 18S, TUA and RPS were found to
      be generally unreliable as reference genes. Our results provide a basis for the
      future selection of reference genes for biological research with Chinese prickly
      ash, under a variety of conditions.

PMID- 29601543
TI  - The Design of 3D-Printed Lattice-Reinforced Thickness-Varying Shell Molds for
      Castings.
AB  - 3D printing technologies have been used gradually for the fabrication of sand
      molds and cores for castings, even though these molds and cores are dense
      structures. In this paper, a generation method for lattice-reinforced thickness
      varying shell molds is proposed and presented. The first step is the
      discretization of the STL (Stereo Lithography) model of a casting into finite
      difference meshes. After this, a shell is formed by surrounding the casting with
      varying thickness, which is roughly proportional to the surface temperature
      distribution of the casting that is acquired by virtually cooling it in the
      environment. A regular lattice is subsequently constructed to support the shell.
      The outside surface of the shell and lattice in the cubic mesh format is then
      converted to STL format to serve as the external surface of the new shell mold.
      The internal surface of the new mold is the casting's surface with the normals of
      all of the triangles in STL format reversed. Experimental verification was
      performed on an Al alloy wheel hub casting. Its lattice-reinforced thickness
      varying shell mold was generated by the proposed method and fabricated by the
      binder jetting 3D printing. The poured wheel hub casting was sound and of good
      surface smoothness. The cooling rate of the wheel hub casting was greatly
      increased due to the shell mold structure. This lattice-reinforced thickness
      varying shell mold generation method is of great significance for mold design for
      castings to achieve cooling control.

PMID- 29601542
TI  - Identification and Comparison of Constituents of Aurantii Fructus and Aurantii
      Fructus Immaturus by UFLC-DAD-Triple TOF-MS/MS.
AB  - Although Aurantii Fructus (AF) and Aurantii Fructus Immaturus (AFI) are both the
      fruits of the same rutaceae plant at different stages of growth, they exert
      similar yet distinct clinical effects. The chemical composition is crucial for
      quality control as well as therapeutic application. To address this concern, it
      is significant to evaluate the similarities and differences of the constituents
      in both AF and AFI. The extract of AF and AFI were comprehensively analyzed by
      ultra fast liquid chromatography-photodiode array detector-triple-time of flight
      tandem mass spectrometry (UFLC-DAD-Triple TOF-MS/MS). Among the 40 compounds
      detected, 19 metabolites were detected in both the AF and AFI; whereas 13
      compounds were only detected in AF and five constituents were exclusively
      detected in AFI. In particular, even in AFI, three compounds were only identified
      in AFI (Citrus aurantium' L. and its cultivar). Among the 18 compounds confirmed
      by standard database, 13 compounds were reported in AF and AFI for the first
      time. Furthermore, the distinction was also revealed by the content of naringin,
      hesperidin, neohesperidin, and synephrine. The study directly contributed to the
      similarities and differences of AF and AFI. Herein, similarities and the
      differences in chemical profiles of AF and AFI could explain the current clinical
      applications.

PMID- 29601545
TI  - Microstructure and Mechanical Properties of Al2O3/Er3Al5O12 Binary Eutectic
      Ceramic Prepared by Bridgman Method.
AB  - Directionally solidified Al2O3/Er3Al5O12 (EAG) eutectic ceramic was prepared via
      vertical Bridgman method with high-frequency induction heating. The effects of
      the growth rate on the microstructure and mechanical properties of the solidified
      ceramic were investigated. The experimental results showed that there were no
      pores or amorphous phases in the directionally solidified Al2O3/EAG eutectic
      ceramic. Al2O3 phase was embedded in the EAG matrix phase, and the two phases
      were intertwined with each other to form a typical binary eutectic "hieroglyphic"
      structure. With the increase of growth rate, the phase size and spacing of the
      solidified Al2O3/EAG ceramic both decreased, and the growth rate and phase
      spacing satisfied the lambda2v ~ 60 formula of Jackson-Hunt theory. The cross
      section microstructure of the solidified ceramic always exhibited an irregular
      eutectic growth, while the longitudinal section microstructure presented a
      directional growth. The mechanical properties of the solidified ceramic gradually
      increased with the increase of growth rate, and the maximum hardness and fracture
      toughness could reach 21.57 GPa and 2.98 MPa.m1/2 respectively. It was considered
      that the crack deflection and branching could enhance the toughness of the
      solidified ceramic effectively.

PMID- 29601544
TI  - Influence of Mothers' Nutrition Knowledge and Attitudes on Their Purchase
      Intention for Infant Cereal with No Added Sugar Claim.
AB  - A higher sugar intake in infancy might result in a predisposition to a higher
      sugar intake in later childhood. In Taiwan, many commercial infant and toddler
      foods with nutrition claims have high sugar content. This study explored the
      influence of mothers' knowledge and attitudes on their purchase intention for
      infant food with nutrition claims. This study was a cross-sectional survey. An
      online survey was distributed to 940 mothers who had a child aged between 4
      months and 3 years; 40% of mothers tend to misunderstand that "no added sugar"
      (NAS) indicates no sugar or less sugar content and, thus, that NAS infant cereal
      is healthy. Approximately 50-70% of mothers believe that NAS infant cereal is
      more natural, healthier, and contains less sugar. Attitude toward the NAS claim
      was found to be a mediating variable between sugar-related knowledge and purchase
      intention. The lower the level of sugar-related knowledge was, the more positive
      the attitude toward NAS infant cereal and the higher the purchase intention for
      NAS infant cereal were. In the future, regulation of no added sugar is needed to
      avoid the misleading information and mothers' sugar-related knowledge need to be
      improved through nutrition education.

PMID- 29601546
TI  - Assessing Vulnerability to Urban Heat: A Study of Disproportionate Heat Exposure
      and Access to Refuge by Socio-Demographic Status in Portland, Oregon.
AB  - Extreme urban heat is a powerful environmental stressor which poses a significant
      threat to human health and well-being. Exacerbated by the urban heat island
      phenomenon, heat events are expected to become more intense and frequent as
      climate change progresses, though we have limited understanding of the impact of
      such events on vulnerable populations at a neighborhood or census block group
      level. Focusing on the City of Portland, Oregon, this study aimed to determine
      which socio-demographic populations experience disproportionate exposure to
      extreme heat, as well as the level of access to refuge in the form of public
      cooling centers or residential central air conditioning. During a 2014 heat wave,
      temperature data were recorded using a vehicle-traverse collection method, then
      extrapolated to determine average temperature at the census block group level.
      Socio-demographic factors including income, race, education, age, and English
      speaking ability were tested using statistical assessments to identify
      significant relationships with heat exposure and access to refuge from extreme
      heat. Results indicate that groups with limited adaptive capacity, including
      those in poverty and non-white populations, are at higher risk for heat exposure,
      suggesting an emerging concern of environmental justice as it relates to climate
      change. The paper concludes by emphasizing the importance of cultural sensitivity
      and inclusion, in combination with effectively distributing cooling centers in
      areas where the greatest burden befalls vulnerable populations.

PMID- 29601547
TI  - Impact of Interstitial Ni on the Thermoelectric Properties of the Half-Heusler
      TiNiSn.
AB  - TiNiSn is an intensively studied half-Heusler alloy that shows great potential
      for waste heat recovery. Here, we report on the structures and thermoelectric
      properties of a series of metal-rich TiNi1+ySn compositions prepared via solid
      state reactions and hot pressing. A general relation between the amount of
      interstitial Ni and lattice parameter is determined from neutron powder
      diffraction. High-resolution synchrotron X-ray powder diffraction reveals the
      occurrence of strain broadening upon hot pressing, which is attributed to the
      metastable arrangement of interstitial Ni. Hall measurements confirm that
      interstitial Ni causes weak n-type doping and a reduction in carrier mobility,
      which limits the power factor to 2.5-3 mW m-1 K-2 for these samples. The thermal
      conductivity was modelled within the Callaway approximation and is quantitively
      linked to the amount of interstitial Ni, resulting in a predicted value of 12.7 W
      m-1 K-1 at 323 K for stoichiometric TiNiSn. Interstitial Ni leads to a reduction
      of the thermal band gap and moves the peak ZT = 0.4 to lower temperatures, thus
      offering the possibility to engineer a broad ZT plateau. This work adds further
      insight into the impact of small amounts of interstitial Ni on the thermal and
      electrical transport of TiNiSn.

PMID- 29601549
TI  - Accurate Object Pose Estimation Using Depth Only.
AB  - Object recognition and pose estimation is an important task in computer vision. A
      pose estimation algorithm using only depth information is proposed in this paper.
      Foreground and background points are distinguished based on their relative
      positions with boundaries. Model templates are selected using synthetic scenes to
      make up for the point pair feature algorithm. An accurate and fast pose
      verification method is introduced to select result poses from thousands of poses.
      Our algorithm is evaluated against a large number of scenes and proved to be more
      accurate than algorithms using both color information and depth information.

PMID- 29601550
TI  - Exploration of the Use of New Psychoactive Substances by Individuals in Treatment
      for Substance Misuse in the UK.
AB  - Substance misuse services need to meet the growing demand and needs of
      individuals using new psychoactive substances (NPS). A review of the literature
      identified a paucity of research regarding NPS use by these individuals and UK
      guidelines outline the need for locally tailored strategies. The purpose of this
      qualitative study was to identify and explore key themes in relation to the use
      of NPS by individuals receiving community treatment for their substance use.
      Electronic records identified demographics and semi-structured interviews were
      undertaken. A thematic analysis of transcripts identified a variety of substance
      use histories; 50% were prescribed opiate substitutes and 25% used NPS as a
      primary substance. All were males, age range 26-59 years (SD = 9), who
      predominantly smoked cannabinoids and snorted/injected stimulant NPS. The type of
      NPS used was determined by affordability, availability, side-effect profile and
      desired effects (physical and psychological: 25% reported weight loss as
      motivation for their use). Poly-pharmacy, supplementation and displacement of
      other drugs were prevalent. In conclusion, NPS use and associated experiences
      vary widely among people receiving substance use treatment. Development of
      effective recovery pathways should be tailored to individuals, and include harm
      reduction strategies, psychosocial interventions, and effective signposting.
      Services should be vigilant for NPS use, "on top" use and diversion of
      prescriptions.

PMID- 29601548
TI  - Roles of NF-kappaB Signaling in the Regulation of miRNAs Impacting on
      Inflammation in Cancer.
AB  - The NF-kappaB family of transcription factors regulate the expression of genes
      encoding proteins and microRNAs (miRNA, miR) precursors that may either
      positively or negatively regulate a variety of biological processes such as cell
      cycle progression, cell survival, and cell differentiation. The NF-kappaB-miRNA
      transcriptional regulatory network has been implicated in the regulation of
      proinflammatory, immune, and stress-like responses. Gene regulation by miRNAs has
      emerged as an additional epigenetic mechanism at the post-transcriptional level.
      The expression of miRNAs can be regulated by specific transcription factors
      (TFs), including the NF-kappaB TF family, and vice versa. The interplay between
      TFs and miRNAs creates positive or negative feedback loops and also regulatory
      networks, which can control cell fate. In the current review, we discuss the
      impact of NF-kappaB-miRNA interplay and feedback loops and networks impacting on
      inflammation in cancer. We provide several paradigms of specific NF-kappaB-miRNA
      networks that can regulate inflammation linked to cancer. For example, the NF
      kappaB-miR-146 and NF-kappaB-miR-155 networks fine-tune the activity, intensity,
      and duration of inflammation, while the NF-kappaB-miR-21 and NF-kappaB-miR-181b-1
      amplifying loops link inflammation to cancer; and p53- or NF-kappaB-regulated
      miRNAs interconnect these pathways and may shift the balance to cancer
      development or tumor suppression. The availability of genomic data may be useful
      to verify and find novel interactions, and provide a catalogue of 162 miRNAs
      targeting and 40 miRNAs possibly regulated by NF-kappaB. We propose that studying
      active TF-miRNA transcriptional regulatory networks such as NF-kappaB-miRNA
      networks in specific cancer types can contribute to our further understanding of
      the regulatory interplay between inflammation and cancer, and also perhaps lead
      to the development of pharmacologically novel therapeutic approaches to combat
      cancer.

PMID- 29601551
TI  - Kinetics and Thermodynamics of DNA Processing by Wild Type DNA-Glycosylase Endo
      III and Its Catalytically Inactive Mutant Forms.
AB  - Endonuclease III (Endo III or Nth) is one of the key enzymes responsible for
      initiating the base excision repair of oxidized or reduced pyrimidine bases in
      DNA. In this study, a thermodynamic analysis of structural rearrangements of the
      specific and nonspecific DNA-duplexes during their interaction with Endo III is
      performed based on stopped-flow kinetic data. 1,3-diaza-2-oxophenoxazine (tCO), a
      fluorescent analog of the natural nucleobase cytosine, is used to record
      multistep DNA binding and lesion recognition within a temperature range (5-37 
      degrees C). Standard Gibbs energy, enthalpy, and entropy of the specific steps
      are derived from kinetic data using Van't Hoff plots. The data suggest that
      enthalpy-driven exothermic 5,6-dihydrouracil (DHU) recognition and desolvation
      accompanied entropy-driven adjustment of the enzyme-substrate complex into a
      catalytically active state play equally important parts in the overall process.
      The roles of catalytically significant amino acids Lys120 and Asp138 in the DNA
      lesion recognition and catalysis are identified. Lys120 participates not only in
      the catalytic steps but also in the processes of local duplex distortion, whereas
      substitution Asp138Ala leads to a complete loss of the ability of Endo III to
      distort a DNA double chain during enzyme-DNA complex formation.

PMID- 29601552
TI  - Classification of Incomplete Data Based on Evidence Theory and an Extreme
      Learning Machine in Wireless Sensor Networks.
AB  - In wireless sensor networks, the classification of incomplete data reported by
      sensor nodes is an open issue because it is difficult to accurately estimate the
      missing values. In many cases, the misclassification is unacceptable considering
      that it probably brings catastrophic damages to the data users. In this paper, a
      novel classification approach of incomplete data is proposed to reduce the
      misclassification errors. This method uses the regularized extreme learning
      machine to estimate the potential values of missing data at first, and then it
      converts the estimations into multiple classification results on the basis of the
      distance between interval numbers. Finally, an evidential reasoning rule is
      adopted to fuse these classification results. The final decision is made
      according to the combined basic belief assignment. The experimental results show
      that this method has better performance than other traditional classification
      methods of incomplete data.

PMID- 29601555
TI  - ["Danger theory" as a common mechanism of sarcoidosis induction by infectious and
      non-infectious factors - a role of genetics factors].
AB  - In the light of modified the Matzinger's model of immune response, human heat
      shock proteins (hsp) as main 'danger signals' (tissue damage-associated molecular
      patterns-DAMPs) or/and microbial hsp as pathogen-associated molecular patterns
      (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid
      granuloma by both infectious and non-infectious factors in genetically different
      predisposed host.

PMID- 29601553
TI  - Dietary Patterns of Children and Adolescents from High, Medium and Low Human
      Development Countries and Associated Socioeconomic Factors: A Systematic Review.
AB  - The purpose of this systematic review is to assess the associations among
      education, income and dietary pattern (DP) in children and adolescents from high,
      medium and low human development countries (HHDC, MHDC and LHDC, respectively).
      Observational studies that evaluated the association between family income or
      education with the DP are obtained through electronic database searches. Forty
      articles are selected for review. In HHDC, education is inversely associated with
      "unhealthy" DP and positively associated with "healthy" DP. In cross-sectional
      studies from HHDC, higher income is negatively associated with "unhealthy" DP. In
      MHDC, there is no association between the socioeconomic variables (SE) and the
      DPs, although, in some studies, the unhealthy diet is positively associated with
      SE. Only one study conducted in LHDC showed an inverse association between
      income/education with "unhealthy" DP and there is no association between the SE
      and "healthy" DP. In conclusion, children and adolescents living in HHDC with
      high parental education tend to have a healthier diet. In MHDC, although an
      unhealthy diet is found among the high-income and educated population, the
      associations are not clear. Additional research is needed to clarify the
      associations between income and education with "unhealthy" and "healthy" DPs in
      MHDC and LHDC.

PMID- 29601556
TI  - ["Danger theory"as a common mechanism of sarcoidosis induction by infectious and
      non- infectious factors - a role of environmental factors and autoimmunity].
AB  - In the light of modified the Matzinger's model of immune response, human heat
      shock proteins (hsp) as main "danger signals" tissue damage-associated molecular
      patterns (DAMPs) or/and microbial hsp as pathogen-associated molecular patterns
      (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid
      granuloma by both infectious and non-infectious factors in genetically different
      predisposed host. Regarding infectious causes of sarcoid models, low-virulence
      strains of, e.g. mycobacteria and propionibacteria recognized through genetically
      changed PRR and persisting in genetically altered host phagocytes, generate
      increased release of both human and microbial hsp with their molecular and
      functional homology. High chronic spread of human and microbial hsp altering
      cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative
      stress, induces the autoimmunity, considered in sarcoidosis. Regarding non
      infectious causes of sarcoidosis, human hsp may be released at high levels during
      chronic low-grade exposure to misfolding amyloid precursor protein in stressed
      cells, phagocyted metal fumes, pigments with/ without aluminum in tattoos, and
      due to heat shock in firefighters. Therefore, human hsp as DAMPs and/or microbial
      hsp as PAMPs produced as a result of non-infectious and infectious factors may
      induce different models of sarcoidosis, depending on the genetic background of
      the host.

PMID- 29601554
TI  - Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current
      Standard and beyond.
AB  - Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL),
      remains one of the most curable cancers in the paediatric setting; multi-agent
      chemotherapy cures approximately 65-90% of patients. Over the last two decades,
      major efforts have focused on improving the survival rate by intensification of
      combination chemotherapy regimens and employing stem cell transplantation for
      chemotherapy-resistant patients. More recently, several new and 'renewed' agents
      have offered the opportunity for a change in the paradigm for the management of
      both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK
      inhibitors following the identification of the EML4-ALK fusion gene in Non-Small
      Cell Lung Cancer (NSCLC) has opened new possibilities for ALK-positive ALCL. The
      uniform expression of CD30 on the cell surface of ALCL has given the opportunity
      for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown
      remarkable activity as a single agent even in the face of relapsed disease, has
      led to the consideration of a revised approach to frontline therapy. The advent
      of immune therapies such as checkpoint inhibition has provided another option for
      the treatment of ALCL. In fact, the number of potential new agents now presents a
      real challenge to the clinical community that must prioritise those thought to
      offer the most promise for the future. In this review, we will focus on the
      current status of paediatric ALCL therapy, explore how new and 'renewed' agents
      are re-shaping the therapeutic landscape for ALCL, and identify the strategies
      being employed in the next generation of clinical trials.

PMID- 29601557
TI  - [The diagnostic algorithm of practice in pulmonary and extrapulmonary
      sarcoidosis].
AB  - Sarcoidosis (SA) is a granulomatous multisystem disease of unknown ethiology.
      Pulmonary, lymphadenopathy, liver, spleen, skin, and bone sarcoidosis are more
      frequent but also SA of the heart, central nervous system, eye, and hypercalcemia
      with following kidney failure also occur. Sarcoidosis may co-exist with
      extrapulmonary forms, which may overtake or precede each other. SA may occur as
      acute or chronic with the possibility of complete remission in the early stages
      of disease. Due to frequent occurrence of asymptomatic SA in threatening vital
      organs a diagnostic algorithm of practice in pulmonary and extrapulmonary
      sarcoidosis has been proposed by the author of the article. Diagnosis of SA is
      based on a correlation of clinical, radiological and histopathological pictures
      with the presence of non-caseating granuloma in material from the biopsy from at
      least one organ and having excluded tuberculosis. In all forms of SA, USG
      abdomen, ECG, ECHO heart, blood tests (blood count, calcium, creatinine,
      transaminases), level of calcium in a 24-hour urine samples, ophtalmoscopic
      examinations and lung function tests in pulmonary sarcoidosis should be
      undertaken to avoid overlooking any form of SA, especially in threatened vital
      organs. For this purpose, the multidisciplinary team providing an adequate care
      to the patient with SA has been created by the author of the article has been
      created by the author of the article in the University Clinical Center in Gdansk
      providing comprehensive care to patients with sarcoidosis.

PMID- 29601558
TI  - [Differentiation of dyspnea in patients with asthma and lung sarcoidosis].
AB  - Dyspnea as a subjective feeling of lack of air is the patients with the pathology
      of the respiratory system. Objectivization of this phenomenon is difficult,
      despite the introduction of questionnaires about the degree of dyspnoea. The
      results of these assessments do not always correlate with the results of
      spirometric tests. In patients with asthma, dyspnoea is caused by airway
      obstruction. In the case of patients with lung sarcoidosis, the complexity of the
      phenomenon causes that many mechanisms and factors are responsible for the
      dyspnea symptoms in these patients. Dyspnea in patients with sarcoidosis is
      progressive and is closely related to the extent of interstitial exchanges. The
      diffusion capacity for carbon monoxide (DLco) determined in these patients
      reflects the degree of respiratory distress. Therapeutic procedures are also
      dependent on this parameter.

PMID- 29601559
TI  - [Advances in endoscopic diagnosis of sarcoidosis].
AB  - A diagnosis of pulmonary sarcoidosis is based on the assessment of clinical
      outcome, radiology findings and detection of noncaseating granulomas in cytology
      or histology specimens. Cytological material obtained from enlarged lymph nodes
      and/or histological specimens from bronchial mucosa and lung tissue are examined
      according to sarcoidosis stage. The most available are standard bronchoscopic
      methods as conventional transbronchial needle aspiration (cTBNA), endobronchial
      biopsy (EBB) and transbronchial lung biopsy (TBLB) both performed with use of
      forceps. The new endoscopic techniques introduced to pulmonary diagnostics are:
      endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) and
      endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or if used by the
      ultrasound bronchoscope (EUS-b-FNA) and transbronchial lung cryobiopsy (TBLC).
      Considering a dynamic improvement in cytology assessment techniques (processed as
      cytology smears and cell blocks) the endoscopic methods with use of fine needle
      aspiration biopsy of enlarged lymph nodes became a method of choice in
      sarcoidosis with lymphadenopathy, and published data suggest a higher diagnostic
      yield when performed under endosonographic guidance. The optimal approach
      (transbronchial or transesophageal) and the selection of mediastinal lymph node
      stations considered for biopsy still need evaluation. Also TBLC, successfully
      used in the diagnosis of other diffuse parenchymal lung diseases, requires more
      experiences and trials to establish its role in diagnosis of pulmonary
      sarcoidosis.

PMID- 29601560
TI  - [Radiological examinations in the diagnosis and monitoring of pulmonary
      sarcoidosis].
AB  - Diagnosis of sarcoidosis is mainly based on radiological examinations. The most
      important one is chest X-ray, which in typical cases reveals bilateral enlarged
      hilar lymph nodes, in a proportion of patients also concomitant parenchymal
      changes, rarely isolated parenchymal infiltrations or signs of lung fibrosis. The
      next step is chest computed tomography (CT), most often of high resolution,
      although strict indications for CT have been defined. Monitoring of sarcoidosis
      is based on the assessment of serial chest X-ray examinations. Indications for CT
      in a patient with completed diagnosis are limited. Positron emission tomography
      (PET) is a valuable tool for the evaluation of especially difficult diagnostic
      cases, for the assessment of disease activity, identification of yet unidentified
      extrapulmonary locations or selection of an optimal place for biopsy. In the
      present paper you will find how to use these radiological techniques for the
      diagnosis and monitoring of sarcoidosis.

PMID- 29601561
TI  - [Cardiac sarcoidosis: diagnostics, treatment and follow-up].
AB  - Sarcoidosis is a generalised granulomatous disorder of unknown aetiology. Cardiac
      involvement may affect conduction system, myocardium, valvular apparatus and
      pericardium. Clinical spectrum ranges from asymptomatic involvement to sudden
      cardiac death. Patients with biopsy-proven extracardiac sarcoidosis should be
      screened for cardiac involvement (standard ECG, 24-hour Holter ECG,
      echocardiography) and in case of any abnormalities found on these tests, more
      advanced diagnostic methods should be used. Steroid treatment is still the
      mainstay of therapy in cardiac sarcoidosis. Several immunosuppresive agents are
      also effective and used in different combinations with steroids, as well as heart
      failure treatment (including ACE inhibitors, angiotensin receptor blockers, beta
      blockers and diuretics). Advanced heart block requires pacemaker implantation,
      and implantable cardioverterdefibrillator is an effective treatment in primary
      and secondary prophylaxis of sudden cardiac death. Heart transplantation is
      considered in advanced, drug-resistant heart failure or incessant ventricular
      arrhythmias unresponsive to other forms of therapy.

PMID- 29601562
TI  - [Neurosarcoidosis - diagnosis, clinical picture and therapy].
AB  - Sarcoidosis (SA) is a granulomatous, multisystem disease of unknown etiology.
      Most often the disease affects lungs and mediastinal lymph nodes, but it may
      occur in other organs. Neurosarcoidosis (NS) more commonly occurs with other
      sarcoidosis forms, in 1% of cases it involves only nervous system. Symptomatic NS
      occurs but on autopsy study up to 25% of cases are confirmed. NS can affect
      central nervous system: the brain, spinal cord and peripheral nerves, and
      muscles. The diagnosis of neurosarcoidosis facilitates diagnostic criteria:
      histopathological, imaging and cerebrospinal fluid examination, and clinical
      symptoms. At present, there are no set standards for treatment of patients
      suffering from NS. Early therapy of symptomatic patients is recommended.
      Corticosteroids still are the first line of treatment for NS patients. In cases
      of steroids resistance, lack of their effectiveness or existence of
      contraindication to their use, immunosuppressant treatment is recommended. The
      latest NS algorithm with immunosuppressive treatment is discussed.

PMID- 29601563
TI  - [Advances in differential diagnosis and treatment of patients with sarcoidosis].
AB  - The implementation of treatment in patients with sarcoidosis (SA) must be
      associated with the certainty of diagnosis, which is difficult due to the lack of
      unambiguous criteria. Finding the presence of noncaseating granulomas in bioptic
      material is not always indicative of SA. The main point of SA's diagnosis is the
      level of its activity, because only patients in the active stage should be
      qualified for treatment. In therapy, glucocorticosteroids or second-line drugs -
      methotrexate or azathioprine are still recommended. Introduced monoclonal
      antibodies (infliximab, etanercept, adaluimumab, golimumab, rituximab), tested
      for efficacy in other pathologies associated with the formation of granulomas,
      have a limited application in patients with SA. In contrast, anti-fibrotics
      (pirfenidone and nintedanib) are in clinical trials. The latest method of
      controlling the fibrosis of the parenchyma in the course of SA is the use of
      mesenchymal cells obtained from umbilical cord blood. Preliminary results
      indicate a real possibility of using this therapy in patients with SA.

PMID- 29601564
TI  - [Nintedanib in the treatment of fibrosing interstital lung diseases].
AB  - Nintedanib is an intracellular tyrosine kinase inhibitor approved in a treatment
      of idiopathic pulmonary fibrosis. It reduces the annual rate of forced vital
      capacity decline by approximately 50%, that results in slowing of disease
      progression. The drug also reduces the incidence of acute exacerbations of
      idiopathic pulmonary fibrosis. The efficacy of nintedanib was the same in
      different groups of patients, irrespectively to disease status, age, gender and
      race. The most frequent side effects were gastrointestinal, i.e. diarrhea and
      nausea. If they occur symptomatic treatment should be implemented. In case of
      persistent symptoms despite of this, nintedanib dose should be decreased or drug
      interrupted. The research on combination therapy with pirfenidone did not show
      the new adverse drug reactions, there were no changes in pharmacokinetics of both
      drugs. A trend to improve the efficacy of the combination therapy in comparison
      to monotherapy with both drugs was noted, but further research in this field is
      needed. There are also trials of nintedanib in the treatment of other fibrosing
      interstitial lung diseases, i.e. chronic hypersensitivity pneumonitis, stage IV
      sarcoidosis or connective tissue disease related lung disorders.

PMID- 29601565
TI  - [Cutaneous sarcoidosis - a great imitator].
AB  - Skin manifestation occurs in approximately 25% of patients with sarcoidosis and
      is often the first symptom of the disease. The availability of skin biopsy
      material is helpful in establishing the early diagnosis. Cutaneous sarcoidosis is
      characterized by clinical polymorphism and therefore its diagnosis may cause
      dilemma. The systemic sarcoidosis should be excluded in every patient with
      cutaneous sarcoidosis, because systemic involvement has a significant impact on
      course, treatment and prognosis of the disease.

PMID- 29601566
TI  - [Disturbances of calcium metabolism and vitamin D supplementation in sarcoidosis 
      two-way street].
AB  - The role of vitamin D in the human body is not limited only to the regulation of
      calcium metabolism and secondary to the impact on bones. Recent studies have
      shown the influence of vitamin D level on muscles, on the risk of cancer,
      diabetes, hypertension and pulmonary diseases, including granulomatous diseases.
      Sarcoidosis is a granulomatous disease of unknown etiology. Hypercalcemia in the
      course of the disease occurs in up to 10% of cases in the consequence of
      autonomous overproduction of 1,25-dihydroxyvitamin D by macrophages of sarcoid
      granulomas. Hypercalciuria occurs 3-fold more frequent. On the other hand,
      treatment with corticosteroids increases the risk of osteoporosis. Vitamin D
      intake is recommended for prevention of osteoporosis. Such management, in
      sarcoidosis patients, is not so clear because of risk of hypercalcemia. Vitamin D
      supplementation, according to current recommendations for general population, is
      based solely on 25-hydroxyvitamin D level testing. This seems to be not safe in
      the group of sarcoidosis patients. This article discusses the role of vitamin D
      in sarcoidosis patients and current opinion on vitamin D supplementation in this
      group.

PMID- 29601567
TI  - [Rehabilitation of patients with sarcoidosis].
AB  - Comprehensive rehabilitation programs have so far been developed for many chronic
      diseases. It has been proven that their use can be safe and effective in lung
      diseases such as chronic obstructive pulmonary disease. There are still no
      standards of rehabilitation in the group of patients with sarcoidosis available.
      This situation results mainly from a small number of large, randomized studies
      concerning this topic. The available literature, however, allows defining some
      general rules in this field. It also provides evidence for the effectiveness of
      rehabilitation in reducing symptoms, improving the quality of life and prognosis
      in patients with sarcoidosis. Interventions such as endurance and strength
      training, including inspiratory muscle training, have been applied. Further
      research is necessary to confirm these data.

PMID- 29601568
TI  - [Hypersensitivity pneumonitis and idiopathic pulmonary fibrosis - case report].
AB  - Hypersensitivity pneumonitis (HP), called extrinsic allergic alveolitis, is a
      syndrome characterized by diffuse inflammation of lung parenchyma and airways in
      response to the inhalation of antigens to witch the patient has been previously
      sensitized. The clinical presentation of HP have been categorized as acute,
      subacute and chronic. The patient with chronic HP may lack a history of acute
      episodes and usually reports the insidious onset of cough, dyspnoea, fatigue, and
      weight los. Idiopathic pulmonary fibrosis (IPF) is a type of lung disease that
      results in scarring (fibrosis) of the lungs for an unknown reason. Symptoms of
      IPF are the same as in chronic hypersensitivity pneumonitis and differentiation
      may be difficult. We present a case of patient with chronic HP, in whom the
      course of the end stage of the disease mimic acute exacerbations idiopathic
      pulmonary fibrosis.

PMID- 29601569
TI  - Anthropometric Indices Predict the Development of Hypertension in Normotensive
      and Pre-Hypertensive Middle-Aged Women in Tianjin, China: A Prospective Cohort
      Study.
AB  - BACKGROUND The aims of this study were to investigate the relationship between
      optimal anthropometric indices and their cut-off values and the incidence of
      hypertension in a cohort of middle-aged women in China. MATERIAL AND METHODS A
      cohort of 812 women, aged between 40-70 years were recruited between May 2011 and
      June 2013. An ideal baseline blood pressure was defined as <120/80 mmHg; pre
      hypertension was 120-139/80-89 mmHg; hypertension was >=140/>=90 mmHg.
      Anthropometric measurements included waist circumference (WC), body mass index
      (BMI), waist-hip ratio (WHR), and waist-height ratio (WHtR). The cohort was
      divided into an ideal blood pressure group (Group 1) and a pre-hypertensive group
      (Group 2). Two-year follow-up blood pressure measurements were performed.
      Receiver-operating characteristic (ROC) curve analysis determined the optimal
      anthropometric indices and cut-off values for developing hypertension. RESULTS At
      two-year follow-up, hypertension developed in 9.0% (n=31) in Group 1 and 32.3%
      (n=121) in Group 2. Logistic regression analysis showed that in both groups,
      women in the highest quartile for WC, BMI, WHR, and WHtR had a significantly
      increased risk of developing hypertension compared with the lowest quartile
      (P<0.05). ROC curve area under the curve (AUC) for these anthropometric indices
      were greater in Group 1, and for WC in Groups 1 and 2, with the optimal cut-off
      values greater in Group 1. CONCLUSIONS In a cohort of middle-aged women in China,
      anthropometric indices of obesity were predictive of the development of
      hypertension during a two-year follow-up period.

PMID- 29601570
TI  - Integration of postpartum healthcare services for HIV-infected women and their
      infants in South Africa: A randomised controlled trial.
AB  - BACKGROUND: As the number of HIV-infected women initiating lifelong
      antiretroviral therapy (ART) during pregnancy increases globally, concerns have
      emerged regarding low levels of retention in HIV services and suboptimal
      adherence to ART during the postpartum period. We examined the impact of
      integrating postpartum ART for HIV+ mothers alongside infant follow-up within
      maternal and child health (MCH) services in Cape Town, South Africa. METHODS AND
      FINDINGS: We conducted a randomised trial among HIV+ postpartum women aged >=18
      years who initiated ART during pregnancy in the local antenatal care clinic and
      were breastfeeding when screened before 6 weeks postpartum. We compared an
      integrated postnatal service among mothers and their infants (the MCH-ART
      intervention) to the local standard of care (control)-immediate postnatal
      referral of HIV+ women on ART to general adult ART services and their infants to
      separate routine infant follow-up. Evaluation data were collected through medical
      records and trial measurement visits scheduled and located separately from
      healthcare services involved in either arm. The primary trial outcome was a
      composite endpoint of women's retention in ART care and viral suppression (VS)
      (viral load < 50 copies/ml) at 12 months postpartum; secondary outcomes included
      duration of any and exclusive breastfeeding, mother-to-child HIV transmission,
      and infant mortality. Between 5 June 2013 and 10 December 2014, a total of 471
      mother-infant pairs were enrolled and randomised (mean age, 28.6 years; 18%
      nulliparous; 57% newly diagnosed with HIV in pregnancy; median duration of ART
      use at randomisation, 18 weeks). Among 411 women (87%) with primary endpoint data
      available, 77% of women (n = 155) randomised to the MCH-ART intervention achieved
      the primary composite outcome of retention in ART services with VS at 12 months
      postpartum, compared to 56% of women (n = 117) randomised to the control arm
      (absolute risk difference, 0.21; 95% CI: 0.12-0.30; p < 0.001). The findings for
      improved retention in care and VS among women in the MCH-ART intervention arm
      were consistent across subgroups of participants according to demographic and
      clinical characteristics. The median durations of any breastfeeding and exclusive
      breastfeeding were longer in women randomised to the intervention versus control
      arm (6.9 versus 3.0 months, p = 0.006, and 3.0 versus 1.4 months, p < 0.001,
      respectively). For the infants, overall HIV-free survival through 12 months of
      age was 97%: mother-to-child HIV transmission was 1.2% overall (n = 4 and n = 1
      transmissions in the intervention and control arms, respectively), and infant
      mortality was 1.9% (n = 6 and n = 3 deaths in the intervention and control arms,
      respectively), and these outcomes were similar by trial arm. Interpretation of
      these findings should be qualified by the location of this study in a single
      urban area as well as the self-reported nature of breastfeeding outcomes.
      CONCLUSIONS: In this study, we found that integrating ART services into the MCH
      platform during the postnatal period was a simple and effective intervention, and
      this should be considered for improving maternal and child outcomes in the
      context of HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01933477.

PMID- 29601571
TI  - The presence of rNTPs decreases the speed of mitochondrial DNA replication.
AB  - Ribonucleotides (rNMPs) are frequently incorporated during replication or repair
      by DNA polymerases and failure to remove them leads to instability of nuclear DNA
      (nDNA). Conversely, rNMPs appear to be relatively well-tolerated in mitochondrial
      DNA (mtDNA), although the mechanisms behind the tolerance remain unclear. We here
      show that the human mitochondrial DNA polymerase gamma (Pol gamma) bypasses
      single rNMPs with an unprecedentedly high fidelity and efficiency. In addition,
      Pol gamma exhibits a strikingly low frequency of rNMP incorporation, a property,
      which we find is independent of its exonuclease activity. However, the
      physiological levels of free rNTPs partially inhibit DNA synthesis by Pol gamma
      and render the polymerase more sensitive to imbalanced dNTP pools. The
      characteristics of Pol gamma reported here could have implications for forms of
      mtDNA depletion syndrome (MDS) that are associated with imbalanced cellular dNTP
      pools. Our results show that at the rNTP/dNTP ratios that are expected to prevail
      in such disease states, Pol gamma enters a polymerase/exonuclease idling mode
      that leads to mtDNA replication stalling. This could ultimately lead to mtDNA
      depletion and, consequently, to mitochondrial disease phenotypes such as those
      observed in MDS.

PMID- 29601572
TI  - Brugia malayi infection in ferrets - A small mammal model of lymphatic
      filariasis.
AB  - BACKGROUND: The lack of effective short-course therapies for treatment of the
      adult stage of filarial worms is a major limitation in the global effort to
      eliminate lymphatic filariasis. Studies using current small mammal models of
      lymphatic filariasis are limited by difficulties in quantifying adult worm
      numbers and in assessing lymphatic anatomy and function. METHODOLOGY/PRINCIPAL
      FINDINGS: Here, we re-established Brugia malayi infection of ferrets as a model
      for lymphatic filariasis and demonstrated parasitological, immunological, and
      histological parallels with human infection. Subcutaneous injection of L3 larvae
      into a hind-footpad resulted in a mean of 18 adult worms recovered 16 weeks post
      infection, primarily from the draining inguinal and femoral lymphatics of the
      injected limb. Infected ferrets developed microfilaremia, with patency lasting
      from 12-26 weeks post-infection. Quantitative PCR assessing cytokine
      transcription by antigen-stimulated lymph node cells demonstrated a mixed Th1/Th2
      response occurring during early infection. Immunoregulation with production of
      down-regulatory cytokine IL-10 occurred just prior to peak microfilaremia.
      Histological analysis revealed progressive inflammation of the lymphatic vessel
      walls, with intimal thickening and disorganization of collagen fibers.
      Inflammation was observed as early as 8 weeks post-infection and extended into
      the perivascular and subcutaneous tissues by 16 weeks post-infection. Finally, we
      developed a novel ferret PET/CT lymphoscintigraphy method demonstrating
      substantial changes in lymphatic anatomy and function as early as 3 weeks post
      infection, with progression over the course of infection.
      CONCLUSIONS/SIGNIFICANCE: B. malayi infection of ferrets is a robust model of
      human lymphatic filariasis that can be utilized to study efficacy of novel
      antifilarial agents against adult worms residing within lymphatic vessels. In
      conjunction with PET/CT lymphoscintigraphy, this model can also be used to
      investigate pathogenesis of lymphatic dysfunction in lymphatic filariasis and
      efficacy of medications aimed at reversing lymphatic dysfunction after clearance
      of adult worms.

PMID- 29601573
TI  - Ten years of surveillance of the Yulong plague focus in China and the molecular
      typing and source tracing of the isolates.
AB  - Plague, caused by Yersinia pestis, was classified as a reemerging infectious
      disease by the World Health Organization. The five human pneumonic plague cases
      in Yulong County in 2005 gave rise to the discovery of a Yulong plague focus in
      Yunnan province, China. Thereafter, continuous wild rodent plague (sylvatic
      plague) was identified as the main plague reservoir of this focus. In this study,
      the epizootics in Yulong focus were described, and three molecular typing
      methods, including the different region (DFR) analysis, clustered regularly
      interspaced short palindromic repeats (CRISPRs), and the multiple-locus variable
      number of tandem repeats (VNTR) analysis (MLVA) (14+12), were used for the
      molecular typing and source tracing of Y. pestis isolates in the Yulong plague
      focus. Simultaneously, several isolates from the vicinity of Yunnan were used as
      controls. The results showed that during the 10-year period from 2006 to 2016, an
      animal plague epidemic occurred in 6 of those years, and 5 villages underwent an
      animal plague epidemic within a 30-km2 area of the Yulong plague focus. Searching
      for dead mice was the most effective monitoring method in this plague focus. No
      positive sample has been found in 6937 captured live rodents thus far, suggesting
      that the virulence of strains in the Yulong plague focus is stronger and the
      survival time of mice is shorter after infection. Strains from Lijiang, Sichuan
      and Tibet were of the same complex based on a typing analysis of DFR and CRISPR.
      The genetic relationship of Y. pestis illustrated by MLVA "14+12" demonstrates
      that Tibet and Sichuan strains evolved from the strains 1.IN2 (Qinghai, 1970 and
      Tibet, 1976), and Lijiang strains are closer to Batang strains (Batang County in
      Sichuan province, 2011, Himalaya marmot plague foci) in terms of genetic or
      phylogenic relationships. In conclusion, we have a deeper understanding of this
      new plague focus throughout this study, which provides a basis for effective
      prevention and control.

PMID- 29601574
TI  - Dynamic frontotemporal systems process space and time in working memory.
AB  - How do we rapidly process incoming streams of information in working memory, a
      cognitive mechanism central to human behavior? Dominant views of working memory
      focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a
      neurophysiological signature distinct from the PFC. Are these regions
      independent, or do they interact in the service of working memory? We addressed
      this core issue in behavior by recording directly from frontotemporal sites in
      humans performing a visuospatial working memory task that operationalizes the
      types of identity and spatiotemporal information we encounter every day. Theta
      band oscillations drove bidirectional interactions between the PFC and medial
      temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed
      the PFC preferentially during the processing of spatiotemporal information, while
      PFC theta oscillations directed the MTL for all types of information being
      processed in working memory. These findings reveal an MTL theta mechanism for
      processing space and time and a domain-general PFC theta mechanism, providing
      evidence that rapid, dynamic MTL-PFC interactions underlie working memory for
      everyday experiences.

PMID- 29601576
TI  - Topographic effects on dispersal patterns of Phytophthora cinnamomi at a stand
      scale in a Spanish heathland.
AB  - Phytophthora cinnamomi is one of the most important plant pathogens in the world,
      causing root rot in more than a thousand plant species. This observational study
      was carried out on a P. cinnamomi infected heathland of Erica umbellata used as
      goat pasture. The patterns and shapes of disease foci and their distribution were
      described in a spatial and temporal context using an aerial photograph record. A
      set of topographic traits was selected on the basis of a disease dynamic
      hypothesis and their effects on observed spatial disease patterns were analyzed.
      Incipient infections situated in flat terrain expanded as compact circular front
      patterns with a low growth rate. On slopes, disease patches developed more
      rapidly down slope, forming parabolic shapes. The axis direction of the parabolas
      was highly correlated with terrain aspect, while the parabolic amplitude was
      associated with land curvature and slope. New secondary foci appeared over the
      years producing an accelerated increase of the affected surface. These new foci
      were observed in sites where disease density was higher or near sites more
      frequently visited by animals such as the stable or the forage crop. In contrast,
      a smaller number of disease foci occur in areas which animals are reluctant to
      visit, such as where they have a short range of vision. Our results suggest that
      1) the growth of existing P. cinnamomi foci is controlled by a combination of
      root-to-root contact and water flows, 2) the increase in the diseased area arises
      mainly from the multiplication of patches, 3) the formation of new foci is
      mediated by long-distance transport due to the movement of animals and humans
      along certain preferential pathways, and 4) geomorphology and topography traits
      are associated with the epidemiology of this soil-borne pathogen.

PMID- 29601575
TI  - Discovery of genomic intervals that underlie nematode responses to
      benzimidazoles.
AB  - Parasitic nematodes impose a debilitating health and economic burden across much
      of the world. Nematode resistance to anthelmintic drugs threatens parasite
      control efforts in both human and veterinary medicine. Despite this threat, the
      genetic landscape of potential resistance mechanisms to these critical drugs
      remains largely unexplored. Here, we exploit natural variation in the model
      nematodes Caenorhabditis elegans and Caenorhabditis briggsae to discover
      quantitative trait loci (QTL) that control sensitivity to benzimidazoles widely
      used in human and animal medicine. High-throughput phenotyping of albendazole,
      fenbendazole, mebendazole, and thiabendazole responses in panels of recombinant
      lines led to the discovery of over 15 QTL in C. elegans and four QTL in C.
      briggsae associated with divergent responses to these anthelmintics. Many of
      these QTL are conserved across benzimidazole derivatives, but others show drug
      and dose specificity. We used near-isogenic lines to recapitulate and narrow the
      C. elegans albendazole QTL of largest effect and identified candidate variants
      correlated with the resistance phenotype. These QTL do not overlap with known
      benzimidazole target resistance genes from parasitic nematodes and present
      specific new leads for the discovery of novel mechanisms of nematode
      benzimidazole resistance. Analyses of orthologous genes reveal conservation of
      candidate benzimidazole resistance genes in medically important parasitic
      nematodes. These data provide a basis for extending these approaches to other
      anthelmintic drug classes and a pathway towards validating new markers for
      anthelmintic resistance that can be deployed to improve parasite disease control.

PMID- 29601577
TI  - An open source tool for automatic spatiotemporal assessment of calcium transients
      and local 'signal-close-to-noise' activity in calcium imaging data.
AB  - Local and spontaneous calcium signals play important roles in neurons and
      neuronal networks. Spontaneous or cell-autonomous calcium signals may be
      difficult to assess because they appear in an unpredictable spatiotemporal
      pattern and in very small neuronal loci of axons or dendrites. We developed an
      open source bioinformatics tool for an unbiased assessment of calcium signals in
      x,y-t imaging series. The tool bases its algorithm on a continuous wavelet
      transform-guided peak detection to identify calcium signal candidates. The highly
      sensitive calcium event definition is based on identification of peaks in 1D data
      through analysis of a 2D wavelet transform surface. For spatial analysis, the
      tool uses a grid to separate the x,y-image field in independently analyzed grid
      windows. A document containing a graphical summary of the data is automatically
      created and displays the loci of activity for a wide range of signal intensities.
      Furthermore, the number of activity events is summed up to create an estimated
      total activity value, which can be used to compare different experimental
      situations, such as calcium activity before or after an experimental treatment.
      All traces and data of active loci become documented. The tool can also compute
      the signal variance in a sliding window to visualize activity-dependent signal
      fluctuations. We applied the calcium signal detector to monitor activity states
      of cultured mouse neurons. Our data show that both the total activity value and
      the variance area created by a sliding window can distinguish experimental
      manipulations of neuronal activity states. Notably, the tool is powerful enough
      to compute local calcium events and 'signal-close-to-noise' activity in small
      loci of distal neurites of neurons, which remain during pharmacological blockade
      of neuronal activity with inhibitors such as tetrodotoxin, to block action
      potential firing, or inhibitors of ionotropic glutamate receptors. The tool can
      also offer information about local homeostatic calcium activity events in
      neurites.

PMID- 29601578
TI  - HIV induces production of IL-18 from intestinal epithelial cells that increases
      intestinal permeability and microbial translocation.
AB  - Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple
      context dependent functions. We and others have shown that HIV infection is
      accompanied by increased circulating levels of IL-18 along with decreased levels
      of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is
      also accompanied by intestinal inflammation and decreased intestinal integrity as
      measured by intestinal permeability, regeneration and repair. However, little is
      known concerning the relation between high level of IL-18 associated with the
      viral infection and intestinal permeability. Here we demonstrate that HIV
      treatment increases production of IL-18 and decreases that of IL-18BP production
      in human intestinal epithelial cell (IEC) lines. IL-18 causes apoptosis of the
      IEC by activating caspase-1 and caspase-3. It induces epithelial barrier
      hyperpermeability by decreasing and disrupting both tight and adherens junction
      proteins, occludin, claudin 2 and beta-catenin. Disorganization of F-actin was
      also observed in the IEC that were exposed to the cytokine. Moreover IL-18
      decreases transepithelial electrical resistance (TEER) in Caco-2 and increases
      permeability in HT29 monolayers. The cells' treatment with IL-18 causes an
      increase in the expression of phosphorylated myosin II regulatory light-chain (p
      MLC) and myosin light-chain kinase (MLCK), and a decrease in phosphorylated
      Signal Transducer and Activator of Transcription (p-STAT)-5. This increase in p
      MLC is suppressed by a Rho-kinase (ROCK)-specific inhibitor. Interestingly, the
      levels of the cytokine correlate with those of LPS in the circulation in three
      different categories of HIV infected patients (HAART-naive and HAART-treated HIV
      infected individuals, and Elite controls) as well as in healthy controls.
      Collectively, these results suggest that the HIV-induced IL-18 plays a role in
      increased intestinal permeability and microbial translocation observed in HIV
      infected individuals.

PMID- 29601579
TI  - Cell polarity protein Spa2 coordinates Chs2 incorporation at the division site in
      budding yeast.
AB  - Deposition of additional plasma membrane and cargoes during cytokinesis in
      eukaryotic cells must be coordinated with actomyosin ring contraction, plasma
      membrane ingression and extracellular matrix remodelling. The process by which
      the secretory pathway promotes specific incorporation of key factors into the
      cytokinetic machinery is poorly understood. Here, we show that cell polarity
      protein Spa2 interacts with actomyosin ring components during cytokinesis. Spa2
      directly binds to cytokinetic factors Cyk3 and Hof1. The lethal effects of
      deleting the SPA2 gene in the absence of either Cyk3 or Hof1 can be suppressed by
      expression of the hypermorphic allele of the essential chitin synthase II (Chs2),
      a transmembrane protein transported on secretory vesicles that makes the primary
      septum during cytokinesis. Spa2 also interacts directly with the chitin synthase
      Chs2. Interestingly, artificial incorporation of Chs2 into the cytokinetic
      machinery allows the localisation of Spa2 at the site of division. In addition,
      increased Spa2 protein levels promote Chs2 incorporation at the site of division
      and primary septum formation. Our data indicate that Spa2 is recruited to the
      cleavage site to co-operate with the secretory vesicle system and particular
      actomyosin ring components to promote the incorporation of Chs2 into the so
      called 'ingression progression complexes' during cytokinesis in budding yeast.

PMID- 29601580
TI  - Pyrethroid resistance persists after ten years without usage against Aedes
      aegypti in governmental campaigns: Lessons from Sao Paulo State, Brazil.
AB  - BACKGROUND: Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is
      found at high densities in tropical urban areas. The dissemination of this vector
      is partially the consequence of failures in current vector control methods, still
      mainly relying upon insecticides. In the State of Sao Paulo (SP), Brazil, public
      health managers employed pyrethroids against Ae. aegypti adults from 1989 to
      2000, when a robust insecticide resistance monitoring system detected resistance
      to pyrethroids in several Ae. aegypti populations. However, pyrethroids are also
      the preferred compounds engaged in household applications due to their rapid
      knockdown effect, lower toxicity to mammals and less irritating smell.
      METHODOLOGY/PRINCIPAL FINDINGS: We evaluated pyrethroid resistance in Ae. aegypti
      populations over the course of a decade, from 2004 to 2015, after interruption of
      pyrethroid public applications in SP. Qualitative bioassays with papers
      impregnated with a deltamethrin diagnostic dose (DD) performed with insects from
      seven SP municipalities and evaluated yearly from 2006 to 2014, detected
      resistance in most of the cases. Quantitative bioassays were also carried out
      with four populations in 2011, suggesting a positive correlation between
      resistance level and survivorship in the DD bioassays. Biochemical tests
      conducted with seven insect populations in 2006 and 2015, detected increasing
      metabolic alterations of all major classes of detoxifying enzymes, mostly of
      mixed function oxidases. Genotyping of the voltage-gated sodium channel (AaNaV,
      the pyrethroid target-site) with a TaqMan real time PCR based technique was
      performed from 2004 to 2014 in all seven localities. The two kdr mutations,
      Val1016Ile and Phe1534Cys, known to be spread throughout Brazil, were always
      present with a severe decrease of the susceptible allele over time.
      CONCLUSIONS/SIGNIFICANCE: These results are discussed in the context of public
      and domestic insecticide use, the necessity of implementation of a strong
      integrated vector control strategy and the conceptual misunderstanding between
      'vector control' and 'chemical control of vectors'.

PMID- 29601581
TI  - Widespread domain-like perturbations of DNA methylation in whole blood of Down
      syndrome neonates.
AB  - INTRODUCTION: Down syndrome (DS) is the most frequent genetic cause of
      intellectual disability. Despite the fact that more than 50 years have passed
      since the discovery of its genetic aberrations, the exact pathogenesis of the DS
      phenotype has remained largely unexplained. It was recently hypothesized that the
      DS pathogenesis involves complex (epi)genetic, molecular and cellular
      determinants. To date, many reports have addressed epigenetic aberrations
      associated with DS at different developmental stages/ages and tissue types, but
      to our best knowledge not in DS newborns. This study aimed to investigate genome
      wide methylation patterns in DS newborns compared to non-trisomic newborns.
      METHOD: We analyzed blood samples obtained from ten newborns with DS and five age
      matched non-trisomic newborns. Epigenetic profiles were obtained from extracted
      DNA using the Illumina Infinium 450K array. Since aberrant blood cell
      distribution is known to be present in DS, we applied two distinct models: with
      and without correction for estimated blood cell distribution. RESULTS:
      Differentially methylated position (DMP) analysis of the uncorrected model
      detected 19525 significant hits (51,2% hypomethylated). In the corrected model,
      we found 121953 significant DMPs (49,8% hypomethylated). Independent of the used
      model we observed a chromosome 21 dosage effect. Moreover, we detected 46 and 145
      differentially methylated regions in the uncorrected and corrected model
      respectively, both showing hypomethylation overrepresentation. Replication
      analyses of DMPs and DMRs found by Bacalini et al. (2015) showed a large overlap.
      CONCLUSION: In this study, we found methylation profile differences between DS
      newborns and controls reflecting a systematically affected epigenetic profile.
      The observed chromosome 21 dosage effect suggests the involvement of affected
      essential regulatory factors/regions or altered expression of chromatin modeling
      enzymes located on chromosome 21. Additional research is necessary to
      substantiate these hypotheses.

PMID- 29601582
TI  - Cardiovascular disease: The rise of the genetic risk score.
AB  - In a Perspective, Joshua Knowles and Euan Ashley discuss the potential for use of
      genetic risk scores in clinical practice.

PMID- 29601583
TI  - Chronic restraint stress induces excessive activation of primordial follicles in
      mice ovaries.
AB  - Chronic stress is an important factor influencing people's health. It usually
      causes endocrinal disorders and a decline in reproduction in females. Although
      studies of both human and animals suggest a detrimental effect of stress on
      reproduction, the influence of chronic stress on the ovarian reservation and
      follicular development is still not clear. In this study, a chronic restraint
      stress (CRS) mouse model was used to investigate the effect of stress on ovarian
      reservation and follicular development and explore the underlying mechanism. In
      this study, after 8 weeks of CRS, primordial follicles were excessively activated
      in the ovaries of the CRS group compared with the control group. Further results
      showed that the activation of primordial follicles induced by CRS was involved in
      the increasing expression level of Kit ligand and its receptor Kit and the
      activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN)/protein kinase B (Akt) pathway. The corticotropin
      releasing hormone (CRH) is a neuropeptide released due to stress, which plays an
      important role in regulating follicle development. A high level of serum CRH was
      detected in the CRS mouse model, and the real-time polymerase chain reaction
      assay showed that the mRNA level of its main receptor CRHR1increased in the
      ovaries of the CRS mouse group. Moreover, 100nM CRH significantly improved the
      activation of primordial follicles in newborn mouse ovaries in vitro. These
      results demonstrated that CRS could induce immoderate activation of primordial
      follicles accompanied by the activation of Kit-PI3K signaling, in which CRH might
      be an important endocrine factor.

PMID- 29601584
TI  - 2'-O-methylation of the mRNA cap protects RNAs from decapping and degradation by
      DXO.
AB  - The 5' RNA cap structure (m7GpppRNA) is a key feature of eukaryotic mRNAs with
      important roles in stability, splicing, polyadenylation, mRNA export, and
      translation. Higher eukaryotes can further modify this minimal cap structure with
      the addition of a methyl group on the ribose 2'-O position of the first
      transcribed nucleotide (m7GpppNmpRNA) and sometimes on the adjoining nucleotide
      (m7GpppNmpNmpRNA). In higher eukaryotes, the DXO protein was previously shown to
      be responsible for both decapping and degradation of RNA transcripts harboring
      aberrant 5' ends such as pRNA, pppRNA, GpppRNA, and surprisingly, m7GpppRNA. It
      was proposed that the interaction of the cap binding complex with the methylated
      cap would prevent degradation of m7GpppRNAs by DXO. However, the critical role of
      the 2'-O-methylation found in higher eukaryotic cap structures was not previously
      addressed. In the present study, we demonstrate that DXO possesses both decapping
      and exoribonuclease activities toward incompletely capped RNAs, only sparing RNAs
      with a 2'-O-methylated cap structure. Fluorescence spectroscopy assays also
      revealed that the presence of the 2'-O-methylation on the cap structure
      drastically reduces the affinity of DXO for RNA. Moreover, immunofluorescence and
      structure-function assays also revealed that a nuclear localisation signal is
      located in the amino-terminus region of DXO. Overall, these results are
      consistent with a quality control mechanism in which DXO degrades incompletely
      capped RNAs.

PMID- 29601585
TI  - Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for
      Chagas disease vaccine.
AB  - BACKGROUND: Chagas disease, also known as American Trypanosomiasis, is a chronic
      parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that
      affects about 8 million people around the world where more than 25 million are at
      risk of contracting the infection. Despite of being endemic on 21 Latin-American
      countries, Chagas disease has become a global concern due to migratory movements.
      Unfortunately, available drugs for the treatment have several limitations and
      they are generally administered during the chronic phase of the infection, when
      its efficacy is considered controversial. Thus, prophylactic and/or therapeutic
      vaccines are emerging as interesting control alternatives. In this work, we
      proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen
      for vaccine development against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS:
      In a murine model, we analyzed the immune response triggered by different
      immunization protocols based on Tc80 and evaluated their ability to confer
      protection against a challenge with the parasite. Immunized mice developed Tc80
      specific antibodies which were able to carry out different functions such as:
      enzymatic inhibition, neutralization of parasite infection and complement
      mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong
      cell-mediated immunity. Spleen cells from immunized mice proliferated and
      secreted Th1 cytokines (IL-2, IFN-gamma and TNF-alpha) upon re-stimulation with
      rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic
      T lymphocyte activity against one Tc80 MHC-I peptide. Immunization protocols
      conferred protection against a T. cruzi lethal challenge. Immunized groups showed
      a decreased parasitemia and higher survival rate compared with non-immunized
      control mice. Moreover, during the chronic phase of the infection, immunized mice
      presented: lower levels of myopathy-linked enzymes, parasite burden,
      electrocardiographic disorders and inflammatory cells. CONCLUSIONS/SIGNIFICANCE:
      Considering that an early control of parasite burden and tissue damage might
      contribute to avoid the progression towards symptomatic forms of chronic Chagas
      disease, the efficacy of Tc80-based vaccines make this molecule a promising
      immunogen for a mono or multicomponent vaccine against T. cruzi infection.

PMID- 29601587
TI  - Controlling and synchronizing a fractional-order chaotic system using stability
      theory of a time-varying fractional-order system.
AB  - Control and synchronization of fractional-order chaotic systems have attracted
      wide attention due to their numerous potential applications. To get suitable
      control method and parameters for fractional-order chaotic systems, the stability
      analysis of time-varying fractional-order systems should be discussed in the
      first place. Therefore, this paper analyzes the stability of the time-varying
      fractional-order systems and presents a stability theorem for the system with the
      order 0<alpha<1. This theorem is a sufficient condition which can discriminate
      the stability of time-varying systems conveniently. Feedback controllers are
      designed for control and synchronization of the fractional-order Lu chaotic
      system. The simulation results demonstrate the effectiveness of the proposed
      theorem.

PMID- 29601586
TI  - Two new gene clusters involved in the degradation of plant cell wall from the
      fecal microbiota of Tunisian dromedary.
AB  - Dromedaries are capable of digesting plant cell wall with high content of
      lignocellulose of poor digestibility. Consequently, their intestinal microbiota
      can be a source of novel carbohydrate-active enzymes (CAZymes). To the best of
      our knowledge, no data are available describing the biochemical analysis of
      enzymes in dromedary intestinal microbiota. To investigate new hydrolytic enzymes
      from the dromedary gut, a fosmid library was constructed using metagenomic DNA
      from feces of non-domestic adult dromedary camels living in the Tunisian desert.
      High-throughput functional screening of 13756 clones resulted in 47 hit clones
      active on a panel of various chromogenic and non-chromogenic glycan substrates.
      Two of them, harboring multiple activities, were retained for further analysis.
      Clone 26H3 displayed activity on AZO-CM-cellulose, AZCL Carob galactomannan and
      Tween 20, while clone 36A23 was active on AZCL carob galactomannan and AZCL
      barley beta-glucan. The functional annotation of their sequences highlighted
      original metagenomic loci originating from bacteria of the Bacteroidetes/Chlorobi
      group, involved in the metabolization of mannosides and beta-glucans thanks to a
      complete battery of endo- and exo-acting glycoside hydrolases, esterases,
      phosphorylases and transporters.

PMID- 29601588
TI  - ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of
      dynein arms.
AB  - Zinc finger MYND-type-containing 10 (ZMYND10), a cytoplasmic protein expressed in
      ciliated cells, causes primary ciliary dyskinesia (PCD) when mutated; however,
      its function is poorly understood. Therefore, in this study, we examined the
      roles of ZMYND10 using Zmynd10-/-mice exhibiting typical PCD phenotypes,
      including hydrocephalus and laterality defects. In these mutants, morphology, the
      number of motile cilia, and the 9+2 axoneme structure were normal; however, inner
      and outer dynein arms (IDA and ODA, respectively) were absent. ZMYND10 interacted
      with ODA components and proteins, including LRRC6, DYX1C1, and C21ORF59,
      implicated in the cytoplasmic pre-assembly of DAs, whose levels were
      significantly reduced in Zmynd10-/-mice. LRRC6 and DNAI1 were more stable when co
      expressed with ZYMND10 than when expressed alone. DNAI2, which did not interact
      with ZMYND10, was not stabilized by co-expression with ZMYND10 alone, but was
      stabilized by co-expression with DNAI1 and ZMYND10, suggesting that ZMYND10
      stabilized DNAI1, which subsequently stabilized DNAI2. Together, these results
      demonstrated that ZMYND10 regulated the early stage of DA cytoplasmic pre
      assembly by stabilizing DNAI1.

PMID- 29601589
TI  - Influence of full-length dystrophin on brain volumes in mouse models of Duchenne
      muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) affects besides muscle also the brain,
      resulting in memory and behavioral problems. The consequences of dystrophinopathy
      on gross macroscopic alterations are unclear. To elucidate the effect of full
      length dystrophin expression on brain morphology, we used high-resolution post
      mortem MRI in mouse models that either express 0% (mdx), 100% (BL10) or a low
      amount of full-length dystrophin (mdx-XistDeltahs). While absence or low amounts
      of full-length dystrophin did not significantly affect whole brain volume and
      skull morphology, we found differences in volume of individual brain structures.
      The results are in line with observations in humans, where whole brain volume was
      found to be reduced only in patients lacking both full-length dystrophin and the
      shorter isoform Dp140.

PMID- 29601590
TI  - Differential resilience of Amazonian otters along the Rio Negro in the aftermath
      of the 20th century international fur trade.
AB  - Commercial hunting for the international trade in animal hides in the 20th
      century decimated many populations of aquatic wildlife in Amazonia. However,
      impacts varied significantly between different species and regions, depending
      upon hunting intensity, accessibility of habitat, and the inherent resilience of
      various species and their habitats. We investigated the differential responses of
      two Amazonian Mustelid species, the neotropical otter and giant otter, to
      commercial hunting pressure along the upper Rio Negro in Brazil, and examined
      historical factors that influenced spatial and temporal variation in commercial
      exploitation. We analyzed previously unanalyzed data from historical records of
      hide shipments to track changes in hide sales and prices for the two species in
      the late 20th century. We also gathered oral histories from older Baniwa people
      who had witnessed or participated in commercial otter hunting. These
      complimentary data sources reveal how intrinsic biological and social
      characteristics of the two otter species interacted with market forces and
      regional history. Whereas giant otter populations were driven to local or
      regional extinction during the late 20th century by commercial hunting,
      neotropical otters persisted. In recent decades, giant otter populations have
      returned to some parts of the upper Rio Negro, a development which local people
      welcome as part of a generalized recovery of the ecosystems in their territory as
      a result of the banning of animal pelt exports and indigenous land demarcation.
      This paper expands the scope of the field historical ecology and reflects on the
      role of local knowledge in biodiversity conservation.

PMID- 29601591
TI  - Jail, an unappreciated medical home: Assessing the feasibility of a strengths
      based case management intervention to improve the care retention of HIV-infected
      persons once released from jail.
AB  - BACKGROUND: Linkage to and retention in care for US persons living with HIV
      (PLWH) after release from jail usually declines. We know of no rigorously
      evaluated behavioral interventions that can improve this. We hypothesized that a
      strengths-based case management intervention that we developed for PLWH leaving
      jail would increase linkage/retention in care (indicated by receipt of laboratory
      draws) and a suppressed HIV viral load (VL) in the year following release.
      METHODS AND FINDINGS: We conducted a quasi-experimental feasibility study of our
      intervention for PLWH jailed in Atlanta. We recruited 113 PLWH in jail starting
      in 2014. "SUCCESS" (Sustained, Unbroken Connection to Care, Entry Services, and
      Suppression) began in jail and continued post-release. Subjects who started the
      intervention but subsequently began long-term incarcerations were excluded from
      further analysis. Persons who were retained in the intervention group were
      compared to contemporaneously incarcerated PLWH who did not receive the
      intervention. Identities were submitted to an enhanced HIV/AIDS reporting system
      (eHARS) at the state health department to capture all laboratories drawn. Both
      community engagement and care upon jail return were assessed equally. For 44
      intervention participants released to Atlanta, 50% of care occurred on subsequent
      jail stays, as documented with EventFlow software. Forty-five receiving usual
      services only were recruited for comparison. By examining records of jail
      reentries, half of participants and 60% of controls recidivated (range: 1-8
      returns). All but 6 participants in the intervention and 9 subjects in the
      comparison arm had >=1 laboratory recorded in eHARS post-release. Among the
      intervention group, 52% were retained in care (i.e., had two laboratory studies,
      > = 3 months apart), versus 40% among the comparison group (OR = 1.60, 95% CI
      (0.71, 3.81)). Both arms showed improved viral load suppression. CONCLUSIONS:
      There was a trend towards increased retention for PLWH released from jail after
      SUCCESS, compared to usual services. Measuring linkage at all venues, including
      jail-based clinics, fully captured engagement for this frequently recidivating
      population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02185742.

PMID- 29601592
TI  - No significant regulation of bicoid mRNA by Pumilio or Nanos in the early
      Drosophila embryo.
AB  - Drosophila Pumilio (Pum) is a founding member of the conserved Puf domain class
      of RNA-binding translational regulators. Pum binds with high specificity,
      contacting eight nucleotides, one with each of the repeats in its RNA-binding
      domain. In general, Pum is thought to block translation in collaboration with
      Nanos (Nos), which exhibits no binding specificity in isolation but is recruited
      jointly to regulatory sequences containing a Pum binding site in the 3'-UTRs of
      target mRNAs. Unlike Pum, which is ubiquitous in the early embryo, Nos is tightly
      restricted to the posterior, ensuring that repression of its best-characterized
      target, maternal hunchback (hb) mRNA, takes place exclusively in the posterior.
      An exceptional case of Nos-independent regulation by Pum has been described
      repression of maternal bicoid (bcd) mRNA at the anterior pole of the early
      embryo, dependent on both Pum and conserved Pum binding sites in the 3'-UTR of
      the mRNA. We have re-investigated regulation of bcd in the early embryo; our
      experiments reveal no evidence of a role for Pum or its conserved binding sites
      in regulation of the perdurance of bcd mRNA or protein. Instead, we find that Pum
      and Nos control the accumulation of bcd mRNA in testes.

PMID- 29601593
TI  - A sensitive and innovative detection method for rapid C-reactive proteins
      analysis based on a micro-fluxgate sensor system.
AB  - A sensitive and innovative assay system based on a micro-MEMS-fluxgate sensor and
      immunomagnetic beads-labels was developed for the rapid analysis of C-reactive
      proteins (CRP). The fluxgate sensor presented in this study was fabricated
      through standard micro-electro-mechanical system technology. A multi-loop
      magnetic core made of Fe-based amorphous ribbon was employed as the sensing
      element, and 3-D solenoid copper coils were used to control the sensing core.
      Antibody-conjugated immunomagnetic microbeads were strategically utilized as
      signal tags to label the CRP via the specific conjugation of CRP to polyclonal
      CRP antibodies. Separate Au film substrates were applied as immunoplatforms to
      immobilize CRP-beads labels through classical sandwich assays. Detection and
      quantification of the CRP at different concentrations were implemented by
      detecting the stray field of CRP labeled magnetic beads using the newly-developed
      micro-fluxgate sensor. The resulting system exhibited the required sensitivity,
      stability, reproducibility, and selectivity. A detection limit as low as 0.002
      MUg/mL CRP with a linearity range from 0.002 MUg/mL to 10 MUg/mL was achieved,
      and this suggested that the proposed biosystem possesses high sensitivity. In
      addition to the extremely low detection limit, the proposed method can be easily
      manipulated and possesses a quick response time. The response time of our sensor
      was less than 5 s, and the entire detection period for CRP analysis can be
      completed in less than 30 min using the current method. Given the detection
      performance and other advantages such as miniaturization, excellent stability and
      specificity, the proposed biosensor can be considered as a potential candidate
      for the rapid analysis of CRP, especially for point-of-care platforms.

PMID- 29601594
TI  - Proprioception deficits in chronic stroke-Upper extremity function and daily
      living.
AB  - BACKGROUND: Proprioception deficits are common post-stroke and predict poor
      functional outcome. It is unknown if the presence of proprioception deficits is
      negatively associated with the motor and functional ability of the affected upper
      extremity and daily living at the chronic stage post-stroke. AIMS: 1) To describe
      proprioception deficits of individuals with chronic stroke, 2) to correlate the
      severity of proprioception deficits with the motor and functional ability of the
      upper extremity, and 3) to compare independence in basic and instrumental
      activities in daily living (BADL, IADL), upper extremity motor and functional
      abilities between individuals with and without proprioception deficits. METHODS:
      102 adults aged 29-85 years with chronic stroke participated in this cross
      sectional study. The upper extremity was assessed for proprioception (Thumb
      localization Test), motor [Fugl-Meyer Motor Assessment (FMA)] and functional
      ability [Action Research Arm Test (ARAT), Box and Block Test (BBT)], grip
      strength and daily use [Motor Activity Log (MAL)]. Independence in BADL and IADL
      was also assessed. RESULTS: 71 participants had intact proprioception, 31
      participants had mild-moderate proprioception deficits. Negative significant
      (p<.001) correlations were found between the severity of proprioception deficits
      to the motor ability (FMA) (r = -.41), functional ability (ARAT) (r = -.48),
      dexterity (BBT) (r = -.43), grip strength (r = -.41) and daily-use (MAL amount
      and quality) (r = -.55 and r = -.54, respectively) of the affected upper
      extremity. Significant between-group differences were found for BADL, IADL and
      upper extremity measures. CONCLUSION: Proprioception deficits of individuals with
      chronic stroke are negatively associated with upper extremity motor and
      functional abilities and independence in daily living. Therefore, proprioception
      should be assessed at the chronic stage post-stroke.

PMID- 29601595
TI  - Effects of dexamethasone on intracochlear inflammation and residual hearing after
      cochleostomy: A comparison of administration routes.
AB  - Preservation of residual hearing after cochlear implant is an important issue
      with regards to hearing performance. Various methods of steroid administration
      have been widely used in clinical practice to reduce inflammation and preserve
      residual hearing. Here we compare the effect of different routes of dexamethasone
      administration on intracochlear inflammation and residual hearing in guinea pig
      ears. Dexamethasone was delivered into the guinea pigs either through
      intracochlear, intratympanic or systemic route. The intracochlear concentration
      of dexamethasone, residual hearing, inflammatory cytokines and histopathologic
      changes were evaluated over time. A higher intracochlear dexamethasone
      concentration was observed after intracochlear administration than through the
      other routes. Residual hearing was better preserved with local dexamethasone
      administration as was supported by the reduced inflammatory cytokines, more hair
      cell survival and less severe intracochlear fibrosis and ossification
      concurrently seen in the local delivery group than in the systemic group. The
      results demonstrate that local dexamethasone delivery can reduce intracochlear
      inflammation and preserve residual hearing better than in systemically
      administered dexamethasone.

PMID- 29601596
TI  - An anthropometric approach to characterising neonatal morbidity and body
      composition, using air displacement plethysmography as a criterion method.
AB  - BACKGROUND: With the greatest burden of infant undernutrition and morbidity in
      low and middle income countries (LMICs), there is a need for suitable approaches
      to monitor infants in a simple, low-cost and effective manner. Anthropometry
      continues to play a major role in characterising growth and nutritional status.
      METHODS: We developed a range of models to aid in identifying neonates at risk of
      malnutrition. We first adopted a logistic regression approach to screen for a
      composite neonatal morbidity, low and high body fat (BF%) infants. We then
      developed linear regression models for the estimation of neonatal fat mass as an
      assessment of body composition and nutritional status. RESULTS: We fitted
      logistic regression models combining up to four anthropometric variables to
      predict composite morbidity and low and high BF% neonates. The greatest area
      under receiver-operator characteristic curves (AUC with 95% confidence intervals
      (CI)) for identifying composite morbidity was 0.740 (0.63, 0.85), resulting from
      the combination of birthweight, length, chest and mid-thigh circumferences. The
      AUCs (95% CI) for identifying low and high BF% were 0.827 (0.78, 0.88) and 0.834
      (0.79, 0.88), respectively. For identifying composite morbidity, BF% as measured
      via air displacement plethysmography showed strong predictive ability (AUC 0.786
      (0.70, 0.88)), while birthweight percentiles had a lower AUC (0.695 (0.57,
      0.82)). Birthweight percentiles could also identify low and high BF% neonates
      with AUCs of 0.792 (0.74, 0.85) and 0.834 (0.79, 0.88). We applied a sex-specific
      approach to anthropometric estimation of neonatal fat mass, demonstrating the
      influence of the testing sample size on the final model performance. CONCLUSIONS:
      These models display potential for further development and evaluation in LMICs to
      detect infants in need of further nutritional management, especially where
      traditional methods of risk management such as birthweight for gestational age
      percentiles may be variable or non-existent, or unable to detect appropriately
      grown, low fat newborns.

PMID- 29601597
TI  - HMGB1/IL-1beta complexes in plasma microvesicles modulate immune responses to
      burn injury.
AB  - Modulating immune responses to sepsis and trauma remain one of the most difficult
      challenges in modern medicine. Large burn injuries (LBI) are a severe form of
      trauma associated with sepsis, immune impairment, and mortality. Immune
      dysfunction after LBI is complex, involving both enhanced and impaired immune
      activation. The release of Damage-Associated Molecular Patterns (DAMPs), such as
      HMGB1, and cytokines (e.g. IL-1beta) creates an environment of immune dysfunction
      often leading to end organ failure and death. Both HMGB1 and IL-1beta have been
      found to play critical roles in sepsis and post-burn immune dysfunction. HMGB1
      and IL-1beta have been shown previously to form potent complexes in vitro. We
      recently identified the presence of HMGB1/IL-1beta heterocomplexes in human
      tissue. We now find HMGB1/IL-1beta complexes in human and mouse plasma, and
      identify a synergistic role of HMGB1/IL-1beta complexes in post-burn immune
      dysfunction. In both humans and mice, we found that HMGB1 was enriched in plasma
      microvesicles (MVs) after LBI. HMGB1 was found form complexes with IL-1beta.
      Using flow cytometry of mouse plasma MVs, we identified an increase in an
      HMGB1+/IL-1beta+ MVs. Using co-IP, HMGB1 was found to bind the pro-form of IL
      1beta in mouse and human plasma. Pro-IL-1beta, which is traditionally considered
      inactive, became active when complexed with HMGB1. Human THP-1 monocytes treated
      with HMGB1-pro-IL-1beta complexes showed increased transcription of LBI
      associated cytokines IL-6 and IFNbeta along with suppression of iNOS, mimicking
      findings associated with LBI. These findings identify that HMGB1/IL-1beta
      complexes released after burn injuries can modulate immune responses, and
      microvesicles are identified as a novel reservoir for these immune mediators.
      These complexes might serve as novel immune targets for the treatment of systemic
      immune responses due to LBI or other causes of sepsis.

PMID- 29601598
TI  - Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria
      and induce apoptosis.
AB  - Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea by
      evading innate immunity. Colonizing the mucosa of the reproductive tract depends
      on the bacterial outer membrane porin, PorB, which is essential for ion and
      nutrient uptake. PorB is also targeted to host mitochondria and regulates
      apoptosis pathways to promote infections. How PorB traffics from the outer
      membrane of N. gonorrhoeae to mitochondria and whether it modulates innate immune
      cells, such as macrophages, remains unclear. Here, we show that N. gonorrhoeae
      secretes PorB via outer membrane vesicles (OMVs). Purified OMVs contained
      primarily outer membrane proteins including oligomeric PorB. The porin was
      targeted to mitochondria of macrophages after exposure to purified OMVs and wild
      type N. gonorrhoeae. This was associated with loss of mitochondrial membrane
      potential, release of cytochrome c, activation of apoptotic caspases and cell
      death in a time-dependent manner. Consistent with this, OMV-induced macrophage
      death was prevented with the pan-caspase inhibitor, Q-VD-PH. This shows that N.
      gonorrhoeae utilizes OMVs to target PorB to mitochondria and to induce apoptosis
      in macrophages, thus affecting innate immunity.

PMID- 29601599
TI  - VCAM-1 expression is upregulated by CD34+/CD133+-stem cells derived from septic
      patients.
AB  - CD34+/CD133+- cells are a bone marrow derived stem cell population, which
      presumably contain vascular progenitor cells and are associated with improved
      vascular repair. In this study, we investigated whether the adhesion molecules
      ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular adhesion molecule
      1), E-selectin und L-selectin, which are involved in homing of vascular stem
      cells, are upregulated by CD34+/CD133+-stem cells from septic patients and would
      be associated with improved clinical outcome. Peripheral blood mononuclear cells
      from intensive care unit (ICU) patients with (n = 30) and without sepsis (n =
      10), and healthy volunteers (n = 15) were isolated using Ficoll density gradient
      centrifugation. The expression of VCAM-1, ICAM-1, E-selectin and L-selectin was
      detected on CD34+/CD133+-stem cells by flow cytometry. The severity of disease
      was assessed by the Simplified Acute Physiology Score (SAPS) II. Serum
      concentrations of vascular endothelial growth factor (VEGF) and angiopoietin
      (Ang)-2 were determined by Enzyme-linked immunosorbent assay. The expression of
      VCAM-1, ICAM-1, E-selectin and L-selectin by CD34+/CD133+-stem cells was
      significantly upregulated in septic patients, and correlated with sepsis
      severity. Furthermore, high expression of VCAM-1 by CD34+/CD133+-stem cells
      revealed a positive association with mortalitiy (p<0.05). Furthermore,
      significantly higher serum concentrations of VEGF and Ang-2 were found in septic
      patients, however none showed a strong association with survival. Our data
      suggest, that VCAM-1 upregulation on CD34+/CD133+-stem cells could play a crucial
      role in their homing in the course of sepsis. An increase in sepsis severity
      resulted in both and increase in CD34+/CD133+-stem cells and VCAM-1-expression by
      those cells, which might reflect an increase in need for vascular repair.

PMID- 29601600
TI  - The incidence of medically-attended norovirus gastro-enteritis in Japan:
      Modelling using a medical care insurance claims database.
AB  - BACKGROUND: The burden of medically-attended acute gastro-enteritis (MA-AGE) that
      can be attributed to norovirus is not well established in Japan. Using a
      nationwide database of medical care insurance claims, we estimated the incidence
      of medically-attended norovirus-attributable gastroenteritis (MA-NGE) in Japan.
      METHODS: The incidences of MA-NGE outpatient consultations or hospitalization in
      Japan were modelled on seasonal patterns of MA-AGE for unspecified causes derived
      from the Japan Medical Data Center (JMDC) database for the period July 2007 to
      June 2015. RESULTS: Mean age-adjusted annual incidence rates (per 10,000 person
      years) of MA-NGE associated with outpatient care or hospitalization were 389 (95%
      CI 269-558) and 13 (95% CI 9-20), respectively. Highest rates were in children
      under 5 years of age: 1,569 (95% CI 1,325-1,792) for outpatient consultations and
      48 (95% CI 39-56) for hospitalizations. Of all gastroenteritis episodes
      associated with outpatient care or hospitalization, 29% and 31% were attributed
      to norovirus, respectively. Norovirus was estimated to be responsible for
      4,964,000 outpatient visits (95% CI 3,435,000-7,123,000) and 171,000
      hospitalizations (95% CI 110,000-251,000) per year across Japan. CONCLUSIONS:
      Incidence rates of MA-AGE are high in Japan, and norovirus-attributable disease
      is at least as high as in some other developed countries.

PMID- 29601602
TI  - Risk of ischemic stroke in metabolically healthy obesity: A nationwide population
      based study.
AB  - BACKGROUND: Whether metabolically healthy obese (MHO) individuals are at
      increased risk of ischemic stroke is not well known. We investigated the
      association of the MHO phenotype with ischemic stroke. METHODS: A total of
      354,083 adults (age 45.8 +/- 14.2 years) from the Korean National Health
      Insurance Service-National Sample Cohort enrolled in 2004-2008 were followed-up
      for incident ischemic stroke until 2013. Subjects meeting none of the metabolic
      syndrome criteria were classified as 'metabolically healthy'. The cohort was
      categorized into four groups according to obesity and metabolic status:
      metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight
      (MUNW), MHO, and metabolically unhealthy obese (MUO). RESULTS: Ischemic stroke
      was newly diagnosed in 4,884 (1.4%) individuals during a mean follow-up of 7.4 +/
      1.5 years. Stroke incidence rates for the MHNW, MUNW, MHO, and MUO groups were
      0.56, 2.61, 0.61, and 2.76 per 1,000 person-years, respectively. While risk for
      stroke increased significantly in metabolically unhealthy groups, it was not
      increased in MHO compared to the MHNW group on multivariate analysis. In
      metabolically healthy individuals, obesity did not increase the risk for ischemic
      stroke, regardless of the severity of obesity. Meanwhile, in metabolically
      unhealthy individuals, being obese was significantly associated with increased
      risk of stroke. CONCLUSIONS: MHO individuals were not at increased risk for
      ischemic stroke. However, obesity increased risk for ischemic stroke in persons
      with metabolic risk factors; therefore, maintaining normal weight may be more
      important for this population. Also, metabolic unhealthiness showed greater
      association than obesity with stroke.

PMID- 29601601
TI  - Prenylated phloroglucinols from Hypericum scruglii, an endemic species of
      Sardinia (Italy), as new dual HIV-1 inhibitors effective on HIV-1 replication.
AB  - In a search for new potential multitarget anti-HIV compounds from natural
      products, we have identified in Hypericum scruglii, an endemic and exclusive
      species of Sardinia (Italy), a potent plant lead. The phytochemical study of the
      hydroalcoholic extract obtained from its leaves led to the isolation of its most
      abundant secondary metabolites, belonging to different chemical classes. In
      particular, three phloroglucinols derivatives were identified, confirming their
      significance as chemotaxonomic markers of the Hypericum genus. Among them, the 3
      (13-hydroxygeranyl)-1-(2'-methylbutanoyl)phloroglucinol was reported here for the
      first time. All six isolated compounds have been evaluated firstly for the
      inhibition of both Human Immunodeficiency Virus type 1 (HIV-1) Reverse
      Transcriptase (RT)-associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H)
      activities, for the inhibition of HIV-1 integrase (IN) in biochemical assays, and
      also for their effect on viral replication. Among the isolated metabolites, three
      phloroglucinol derivatives and quercitrin were effective on both RT-associated
      RDDP and RNase H activities in biochemical assays. The same active compounds
      affected also HIV-1 IN strand transfer function, suggesting the involvement of
      the RNase H active site. Furthermore, phloroglucinols compounds, included the
      newly identified compound, were able to inhibit the HIV-1 replication in cell
      based assays.

PMID- 29601603
TI  - The bacterial type III-secreted protein AvrRps4 is a bipartite effector.
AB  - Bacterial effector proteins secreted into host plant cells manipulate those cells
      to the benefit of the pathogen, but effector-triggered immunity (ETI) occurs when
      effectors are recognized by host resistance proteins. The RPS4/RRS1 pair
      recognizes the Pseudomonas syringae pv. pisi effector AvrRps4. AvrRps4 is
      processed in planta into AvrRps4N (133 amino acids), homologous to the N-termini
      of other effectors including the native P. syringae pv. tomato strain DC3000
      effector HopK1, and AvrRps4C (88 amino acids). Previous data suggested that
      AvrRps4C alone is necessary and sufficient for resistance when overexpressed in
      heterologous systems. We show that delivering AvrRps4C from DC3000, but not from
      a DC3000 hopK1- strain, triggers resistance in the Arabidopsis accession Col-0.
      Delivering AvrRps4C in tandem with AvrRps4N, or as a chimera with HopK1N, fully
      complements AvrRps4-triggered immunity. AvrRps4N in the absence of AvrRps4C
      enhances virulence in Col-0. In addition, AvrRps4N triggers a hypersensitive
      response in lettuce that is attenuated by coexpression of AvrRps4C, further
      supporting the role of AvrRps4N as a bona fide effector domain. Based on these
      results we propose that evolutionarily, fusion of AvrRps4C to AvrRps4N may have
      counteracted recognition of AvrRps4N, and that the plant RPS4/RRS1 resistance
      gene pair was selected as a countermeasure. We conclude that AvrRps4 represents
      an unusual chimeric effector, with recognition in Arabidopsis by RPS4/RRS1
      requiring the presence of both processed effector moieties.

PMID- 29601604
TI  - An automated quantitative analysis of cell, nucleus and focal adhesion
      morphology.
AB  - Adherent cells sense the physical properties of their environment via focal
      adhesions. Improved understanding of how cells sense and response to their
      physical surroundings is aided by quantitative evaluation of focal adhesion size,
      number, orientation, and distribution in conjunction with the morphology of
      single cells and the corresponding nuclei. We developed a fast, user-friendly and
      automated image analysis algorithm capable of capturing and characterizing these
      individual components with a high level of accuracy. We demonstrate the
      robustness and applicability of the algorithm by quantifying morphological
      changes in response to a variety of environmental changes as well as
      manipulations of cellular components of mechanotransductions. Finally, as a proof
      of-concept we use our algorithm to quantify the effect of Rho-associated kinase
      inhibitor Y-27632 on focal adhesion maturation. We show that a decrease in cell
      contractility leads to a decrease in focal adhesion size and aspect ratio.

PMID- 29601605
TI  - Increased carriage of non-vaccine serotypes with low invasive disease potential
      four years after switching to the 10-valent pneumococcal conjugate vaccine in The
      Netherlands.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in The
      Netherlands in 2006 and was replaced by PHiD-CV10 in 2011. Data on carriage
      prevalence of S. pneumoniae serotypes in children and invasive pneumococcal
      disease (IPD) in children and older adults were collected to examine the impact
      of PCVs on carriage and IPD in The Netherlands. Pneumococcal carriage prevalence
      was determined by conventional culture of nasopharyngeal swabs in 24-month-old
      children in 2015/2016. Data were compared to similar carriage studies in 2005
      (pre-PCV7 introduction), 2009, 2010/2011 and 2012/2013. Invasive pneumococcal
      disease isolates from hospitalized children <5 years and adults >65 years (2004
      2016) were obtained by sentinel surveillance. All isolates were serotyped by
      Quellung. Serotype invasive disease potential was calculated using carriage and
      nationwide IPD data in children. The overall pneumococcal carriage rate was 48%
      in 2015/2016, lower than in 2010/2011 (64%) and pre-vaccination in 2005 (66%).
      Carriage of the previously dominant non-vaccine serotypes 19A and 11A has
      declined since 2010/2011, from 14.2% to 4.6% and 4.2% to 2.7%, respectively,
      whereas carriage of serotypes 6C and 23B has increased (4.2% to 6.7% and 3.9% to
      7.3%), making serotypes 6C and 23B the most prevalent carriage serotypes. IPD
      incidence declined in children (20/100,000 cases in 2004/2006 to 6/100,000 cases
      in 2015/2016) as well as in older adults (63/100,000 cases to 51/100,000 cases).
      Serotypes 6C, 23B and 11A have high carriage prevalence in children, but show low
      invasive disease potential. Serotype 8 is the main causative agent for IPD in
      older adults (11.3%). In conclusion, 10 years after the introduction of
      pneumococcal vaccination in children in The Netherlands shifts in carriage and
      disease serotypes are still ongoing. Surveillance of both carriage and IPD is
      important to assess PCV impact and to predict necessary future vaccination
      strategies in both children and older adults.

PMID- 29601606
TI  - Chronic noise-exposure exacerbates insulin resistance and promotes the
      manifestations of the type 2 diabetes in a high-fat diet mouse model.
AB  - Epidemiological studies have revealed that noise exposure was associated with an
      increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of
      that association remains to be elucidated. The present study is designed to
      examine the effects of chronic noise exposure on the development of T2DM in
      combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise
      exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise
      exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J
      male mice, including worsened glucose intolerance, insulin resistance, fasting
      hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a
      paradoxical impact on fat accumulation and circulating levels of free fatty acid,
      indicating a potential stimulating effect of noise on lipolysis. These results
      provide first in vivo supporting evidence for the causative role of noise
      exposure in diabetogenesis and pinpoint a noise-associated increase in blood free
      fatty acid levels as a possible mediator accelerating the effect of noise on the
      development of insulin resistance and T2DM.

PMID- 29601607
TI  - Internalization of subcellular-scale microfabricated chips by healthy and cancer
      cells.
AB  - Continuous monitoring of physiological parameters inside a living cell will lead
      to major advances in our understanding of biology and complex diseases, such as
      cancer. It also enables the development of new medical diagnostics and
      therapeutics. Progress in nanofabrication and wireless communication has opened
      up the potential of making a wireless chip small enough that it can be wholly
      inserted into a living cell. To investigate how such chips could be internalized
      into various types of living single cells and how this process might affect
      cells' physiology, we designed and fabricated a series of multilayered micron
      scale tag structures with different sizes as potential RFID (Radio Frequency
      IDentification) cell trackers. While the present structures are test structures
      that do not resonate, the tags that do resonate have similar structure from
      device fabrication, material properties, and device size point of view. The
      structures are in four different sizes, the largest with the lateral dimension of
      9 MUm * 21 MUm. The thickness for these structures is kept constant at 1.5 MUm.
      We demonstrate successful delivery of our fabricated chips into various types of
      living cells, such as melanoma skin cancer, breast cancer, colon cancer and
      healthy/normal fibroblast skin cells. To our surprise, we observed a remarkable
      internalization rate difference between each cell type; the uptake rate was
      faster for more aggressive cancer cells than the normal/healthy cells. Cell
      viability before and after tag cellular internalization and persistence of the
      internalized tags have also been recorded over the course of five days of
      incubation. These results establish the foundations of the possibility of long
      term, wireless, intracellular physiological signal monitoring.

PMID- 29601608
TI  - In vitro co-cultures of human gut bacterial species as predicted from co
      occurrence network analysis.
AB  - Network analysis of large metagenomic datasets generated by current sequencing
      technologies can reveal significant co-occurrence patterns between microbial
      species of a biological community. These patterns can be analyzed in terms of
      pairwise combinations between all species comprising a community. Here, we
      construct a co-occurrence network for abundant microbial species encompassing the
      three dominant phyla found in human gut. This was followed by an in vitro
      evaluation of the predicted microbe-microbe co-occurrences, where we chose
      species pairs Bifidobacterium adolescentis and Bacteroides thetaiotaomicron, as
      well as Faecalibacterium prausnitzii and Roseburia inulinivorans as model
      organisms for our study. We then delineate the outcome of the co-cultures when
      equal distributions of resources were provided. The growth behavior of the co
      culture was found to be dependent on the types of microbial species present,
      their specific metabolic activities, and resulting changes in the culture
      environment. Through this reductionist approach and using novel in vitro
      combinations of microbial species under anaerobic conditions, the results of this
      work will aid in the understanding and design of synthetic community
      formulations.

PMID- 29601609
TI  - Withstanding austerity: Equity in health services utilisation in the first stage
      of the economic recession in Southern Spain.
AB  - Scant research is available on the impact of the current economic crisis and
      austerity policies on inequality in health services utilisation in Europe. This
      study aimed to describe the trends in horizontal inequity in the use of health
      services in Andalusia, Spain, during the early years of the Great Recession, and
      the contribution of demographic, economic and social factors. Consultation with a
      general practitioner (GP) and specialist, hospitalisation and emergency care were
      studied through the Andalusian Health Survey 2007 (pre-crisis) and 2011-2012
      (crisis), using a composite income index as socioeconomic status (SES) indicator.
      Horizontal inequity indices (HII) were calculated to take differential healthcare
      needs into account, and a decomposition analysis of change in inequality between
      periods was performed. Results showed that before the crisis, the HII was
      positive (greater access for people with higher SES) for specialist visits but
      negative (greater access for people with lower SES) in the other three
      utilisation models. During the crisis no change was observed in inequalities in
      GP visits, but a pro-poor development was seen for the other types of
      utilisation, with hospital and emergency care showing significant inequality in
      favour of low income groups. Overall, the main contributors to pro-poor changes
      in utilisation were socio-economic variables and poor mental health, due to
      changes in their elasticities. Our findings show that inequalities in healthcare
      utilisation largely remained in favour of the less well-off, despite the cuts in
      welfare benefits and health services provision during the early years of the
      recession in Andalusia. Further research is needed to monitor the potential
      impact of such measures in subsequent years.

PMID- 29601610
TI  - Preventive behaviors adults report using to avoid catching or spreading
      influenza, United States, 2015-16 influenza season.
AB  - INTRODUCTION: Influenza vaccination can prevent influenza and potentially serious
      influenza-related complications. Although the single best way to prevent
      influenza is annual vaccination, everyday preventive actions, including good
      hygiene, health, dietary, and social habits, might help, too. Several preventive
      measures are recommended, including: avoiding close contact with people who are
      sick; staying home when sick; covering your mouth and nose when coughing or
      sneezing; washing your hands often; avoiding touching your eyes, nose, and mouth;
      and practicing other good health habits like cleaning and disinfecting frequently
      touched surfaces, getting plenty of sleep, and drinking plenty of fluids.
      Understanding public acceptance and current usage of these preventive behaviors
      can be useful for planning both seasonal and pandemic influenza prevention
      campaigns. This study estimated the percentage of adults in the United States who
      reported practicing preventive behaviors to avoid catching or spreading
      influenza, and explored associations of reported behaviors with sociodemographic
      factors. METHODS: We analyzed data from 2015 National Internet Flu Survey, a
      nationally representative probability-based Internet panel survey of the non
      institutionalized U.S. population >=18 years. The self-reported behaviors used to
      avoid catching or spreading influenza were grouped into four and three non
      mutually exclusive subgroups, respectively. Weighted proportions were calculated.
      Multivariable logistic regression models were used to calculate adjusted
      prevalence differences and to determine independent associations between
      sociodemographic characteristics and preventive behavior subgroups. RESULTS:
      Common preventive behaviors reported were: 83.2% wash hands often, 80.0% cover
      coughs and sneezes, 78.2% stay home if sick with a respiratory illness, 64.4%
      avoid people sick with a respiratory illness, 51.7% use hand sanitizers, 50.2%
      get treatment as soon as possible, and 49.8% report getting the influenza
      vaccination. Race/ethnicity, gender, age, education, income, region, receipt of
      influenza vaccination, and household size were associated with use of preventive
      behaviors after controlling for other factors. CONCLUSION: Many adults in the
      United States reported using preventive behaviors to avoid catching or spreading
      influenza. Though vaccination is the most important tool available to prevent
      influenza, the addition of preventive behaviors might play an effective role in
      reducing or slowing transmission of influenza and complement prevention efforts.

PMID- 29601612
TI  - Erratum: Screen time and young children: Promoting health and development in a
      digital world.
AB  - [This corrects the article DOI: 10.1093/pch/pxx123.][This corrects the article
      DOI: 10.1093/pch/pxx123.].

PMID- 29601611
TI  - Next generation clinical guidance for primary care in South Africa - credible,
      consistent and pragmatic.
AB  - BACKGROUND: Agreed international development standards underpin high quality de
      novo clinical practice guidelines (CPGs). There is however, no international
      consensus on how high quality CPGs should 'look'; or on whether high quality CPGs
      from one country can be viably implemented elsewhere. Writing de novo CPGs is
      generally resource-intensive and expensive, making this challenging in resource
      poor environments. This paper proposes an alternative, efficient method of
      producing high quality CPGs in such circumstances, using existing CPGs layered by
      local knowledge, contexts and products. METHODS: We undertook a mixed methods
      case study in South African (SA) primary healthcare (PHC), building on findings
      from four independent studies. These comprised an overview of international CPG
      activities; a rapid literature review on international CPG development practices;
      critical appraisal of 16 purposively-sampled SA PHC CPGs; and additional
      interrogation of these CPGs regarding how, why and for whom, they had been
      produced, and how they 'looked'. RESULTS: Despite a common aim to improve SA PHC
      healthcare practices, the included CPGs had different, unclear and inconsistent
      production processes, terminology and evidence presentation styles. None aligned
      with international quality standards. However many included innovative succinct
      guidance for end-users (which we classified as evidence-based summary
      recommendations, patient management tools or protocols). We developed a three
      tiered model, a checklist and a glossary of common terms, for more efficient
      future production of better quality, contextually-relevant, locally-implementable
      SA PHC CPGs. Tier 1 involves transparent synthesis of existing high quality CPG
      recommendations; Tier 2 reflects local expertise to layer Tier 1 evidence with
      local contexts; and Tier 3 comprises tailored locally-relevant end-user guidance.
      CONCLUSION: Our model could be relevant for any resource-poor environment. It
      should reduce effort and costs in finding and synthesising available research
      evidence, whilst efficiently focusing scant resources on contextually-relevant
      evidence-based guidance, and implementation.

PMID- 29601613
TI  - An Acne Survey from the World's Largest Annual Gathering of Twins.
AB  - IMPORTANCE: Surveying identical twins allows us to qualitatively separate genetic
      and environmental factors that may contribute to acne severity. OBJECTIVE: To
      study a cohort of identical and fraternal twins to identify environmental factors
      that may influence acne severity. DESIGN, SETTING, PARTICIPANTS: A survey was
      administered to 139 identical and fraternal twin multiples (279 subjects) at the
      Annual Twins Day Festival in Twinsburg, Ohio on August 6-7, 2016. One set of
      triplets was included. MAIN OUTCOME(S) AND MEASURE(S): Acne incidence, severity,
      and triggers were analyzed using the N-1 Chi-squared test and paired, 2-tailed t
      test. RESULTS: The proportion of concordant pairs was significantly higher in
      identical (64%) vs fraternal (49%) twins (P=0.04). Acne was found to be
      associated with polycystic ovarian syndrome (PCOS; P=0.045), anxiety (P =0.014),
      and asthma (P=0.026). Identical twin pairs with acne had a higher BMI (P= 0.020)
      and exercised significantly less (P=0.001) than those without acne. Analyzing
      concordant twin pairs, the twin with more severe acne was more likely to report
      aggravation of acne with cosmetic product use (P=0.002) and sugar intake
      (P=0.048). CONCLUSIONS AND REVELANCE: This twin study further supports that there
      may be a genetic phenotypic link, though social and environmental factors may
      also have an influence in the disease process. <p><em>J Drugs Dermatol.
      2018;17(4):380-382.</em></p>.

PMID- 29601614
TI  - Dihydroxyacetone: A Review.
AB  - The sunless tanning industry has experienced rapid growth due to public education
      on the dangers of ultraviolet radiation on skin and improvements in products.
      Dihydroxyacetone (DHA) is a 3-carbon sugar allowed by the Food and Drug
      Administration (FDA) as a color additive in sunless tanning products. Bronzers, a
      product removed with soap and water, may also contain DHA. We aim to review the
      literature on DHA. DHA is intended for external application, not including the
      mucous membranes or in or around the eye area. DHA has been used in spray-tan
      booths and by airbrushing it onto consumers, although these are unapproved uses,
      as contact with the color additive is not restricted to the external part of the
      body. Consequently, the FDA recommends customers shield their eyes, lips, and
      mucous membranes, as well as refrain from ingestion or inhalation of DHA. Unlike
      sunscreens, products that protect against ultraviolet radiation and are regulated
      by the FDA as non-prescription drugs, sunless tanning products are regulated as
      cosmetics and cannot provide any protection from exposure to ultraviolet
      radiation. There are reports of non-cosmetic uses of DHA that are not FDA
      approved. With the wide-spread use of DHA, additional studies on its safety are
      warranted. <p><em>J Drugs Dermatol. 2018;17(4):387-391.</em></p>.

PMID- 29601615
TI  - Understanding Patient Experience With Hyperhidrosis: A National Survey of 1,985
      Patients.
AB  - Hyperhidrosis affects 4.8% of the US population, and despite the well documented
      negative impact of hyperhidrosis on patients' lives, data are generally lacking
      on the patient experience with this condition. The International Hyperhidrosis
      Society (IHHS) conducted a study in 2014, and initial results confirmed the
      multifaceted impact of hyperhidrosis on quality of life and underscored the need
      for disease awareness and effective management. To provide further insight into
      the hyperhidrosis patient experience, additional results focusing on family
      history, physician interaction, impact on daily activities, and treatment
      satisfaction are presented here. The online survey included 22 multiple-choice
      questions (some allowing multiple responses). Respondents were IHHS newsletter
      registrants in the US self-identified as suffering with excessive sweating (ie,
      answering 'yes' to Question 1). Of 28,587 survey invitations, a total of 5,042
      recipients (17.6%) opened the e-mail, and 2,045 respondents provided an answer to
      Question 1. Of these, 1,985 (6.9%) self-identified as having excessive sweating
      and continued the survey. Over 18% of survey respondents reported an immediate
      family member with excessive sweating. The top three areas impacted by excessive
      sweating were daily activity, clothing choice, and work/career (average rank
      scores over 3.0 for each area; range 1-8 with lower scores indicating greater
      impact). Nearly half (48.9%) of respondents reported waiting 10 or more years
      prior to seeking medical help, and 85.0% waited at least 3 years. Of the 87.2% of
      respondents who received treatment for hyperhidrosis, patients were most
      satisfied with injections and least satisfied with prescription and over-the
      counter antiperspirants and liposuction. These survey results add important
      clinical insight for the underserved hyperhidrosis patient population. The
      reported delay in seeking proper medical attention highlights the need to
      increase hyperhidrosis awareness among the public and clinicians, to reduce
      stigma associated with the condition, and to encourage active treatment
      strategies. <p><em>J Drugs Dermatol. 2018;17(4):392-396.</em></p>.

PMID- 29601616
TI  - Frontal Fibrosing Alopecia and Concomitant Lichen Planus Pigmentosus: A Case
      Series of Seven African American Women.
AB  - The association of frontal fibrosing alopecia (FFA) and lichen planus pigmentosus
      (LPPigm) is rare. Prior reports suggest that FFA and LPPigm are on the same
      spectrum of disease, and a diagnosis of LPPigm may predict the future development
      of FFA. We aim to further characterize the association between FFA and LPPigm by
      reviewing the clinical cases of seven African American women. Seven patients with
      FFA were diagnosed clinically by recession of frontotemporal hairline and
      confirmed by histopathologic examination showing lymphocyte-mediated cicatricial
      alopecia. LPPigm was diagnosed by clinical evaluation alone based on the
      characteristic morphology, color, and distribution of the lesions. It is
      difficult to distinguish whether halted progression of FFA was due to the success
      of the treatment regimen or spontaneous stabilization of disease over time. Our
      case series supports the theory that FFA and LPPigm likely exist on the same
      spectrum of disease. Our observations demonstrate a likely positive correlation
      between FFA and LPPigm. <p><em>J Drugs Dermatol. 2018;17(4):397-400.</em></p>.

PMID- 29601617
TI  - Collagen Powder in Wound Healing.
AB  - Chronic wounds, such as pressure ulcers, diabetic foot ulcers, and venous leg
      ulcers, are associated with high costs, poor quality of life, and significant
      morbidity and mortality. A chronic wound develops when progression through the
      normal phases of wound healing goes awry, creating a hostile environment with
      elevated levels of pro-inflammatory cytokines, increased matrix
      metalloproteinases (MMPs), destruction of extracellular matrix (ECM) components,
      and diminished activity of growth factors and other soluble mediators. The advent
      of advanced wound care therapies allows for a targeted approach to the treatment
      of nonhealing wounds by addressing specific molecular defects in healing.
      Collagen is an essential building block of the skin that when utilized as an
      adjunctive wound therapy stimulates and recruits immune cells and fibroblasts and
      martyrs itself for degradation by MMPs, thereby preserving native ECM structure
      and promoting healing. Particulate or powdered collagen is processed to minimize
      covalent cross-linking and is purported to exert its biologic activity
      immediately upon application. This article critically reviews the current
      evidence for collagen powder as an adjunctive therapy for chronic wounds and
      presents indications, limitations, and principles of use. In general, there is a
      need for high quality studies and randomized control trials to support its use in
      clinical practice. <p><em>J Drugs Dermatol. 2018;17(4):403-408.</em></p>.

PMID- 29601618
TI  - The Use of a Self-Occluding Topical Anasthetic in Daily Practice: A Non
      Interventional Study.
AB  - INTRODUCTION: A variety of topical anesthetic creams are available to reduce pain
      associated with dermatological procedures. Pliaglis is a self-occluding eutectic
      mixture of lidocaine and tetracaine. STUDY OBJECTIVES: To evaluate the post
      marketing safety profile of Pliaglis and efficacy in terms of pain reduction,
      product satisfaction, and daily practice use prior to pre-defined dermatological
      procedures. METHODS: A prospective, non-interventional study conducted at 44
      sites in four European countries; 581 patients were treated prior to
      dermatological procedures such as pulsed-dye laser therapy, laser-assisted hair
      removal, non-ablative laser resurfacing, dermal filler injections, and vascular
      access. Efficacy was assessed by patients and investigators and included pain
      intensity (visual analogue scale [VAS]), satisfaction, and adequacy of pain
      relief. Safety was evaluated by adverse event (AE) reporting. RESULTS: In 75% of
      the performed procedures, patients scored the pain experienced during the
      procedure as <=30 mm on the VAS and most were very satisfied or satisfied with
      the pain reduction. The investigators assessed the product as providing adequate
      anesthesia in 97% of the performed procedures and were mostly very satisfied or
      satisfied with the convenience of use (79%) and tolerability (95%). Twenty-four
      AEs were reported in 18 (3%) patients. DISCUSSION: Most patients experienced mild
      pain only as evident by the <= 30 mm VAS scores. Patients and investigators were
      aligned with regards to both product satisfaction and their opinion on adequacy
      of pain reduction. The AE frequency was low compared to previous studies,
      possibly relating to different ways of collecting AEs. CONCLUSION: Pliaglis was
      well-tolerated and provided adequate pain reduction prior to dermatological
      procedures. www.clinicaltrials.gov (NCT01800474). <p><em>J Drugs Dermatol.
      2018;17(4):413-418.</em></p> <p>Partial study data have been presented at the
      Anti-Aging Medicine European Congress (AMEC), Paris; October, 24-25, 2014, and
      the European Academy of Dermatology and Venereology (EADV), Istanbul; October 2
      6, 2013.</p>.

PMID- 29601619
TI  - Topical Agents for Scar Management: Are They Effective?
AB  - Scar formation is the body's natural healing response to reestablish dermal
      integrity following an injury. Excessive scarring, however, can cause significant
      cosmetic, functional, and psychological problems. A wide variety of topical
      creams, lotions, and oils are available for scar treatment or wound healing.
      Sieving through the options and selecting the best option for their patients can
      be challenging for clinicians, especially given that clinical evidence for many
      of the active agents in commonly used topical treatments is lacking. The goal of
      this review is to provide an overview of topical treatments utilized for scar
      management, including their mechanism of action and evidence of efficacy. As
      knowledge of the wound healing process is critical to understanding the effects
      of topical treatments, the pathophysiology of wound healing is also reviewed.
      <p><em>J Drugs Dermatol. 2018;17(4):421-425.</em></p>.

PMID- 29601620
TI  - Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and
      Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical,
      Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation.
AB  - BACKGROUND/OBJECTIVES: Anti-aging strategies utilizing stem cells are in the
      forefront. Alpha and beta defensins are natural immune peptides that have been
      shown to activate an LGR6-positive stem cell locus in the hair follicle,
      identified as the source of most new epidermal cells during acute wound healing.
      We investigated the ability of biomimetic alpha and beta defensin molecules,
      supplemented with supportive cosmetic ingredients, formulated into three skin
      care products, at improving the structure and function of aging skin. METHODS: A
      participant- and investigator -blinded, placebo-controlled, multi-center trial
      was performed in outpatient settings. Forty-four healthy female subjects, aged 41
      71 years, skin types I-V, completed the study with 2/3 receiving full formula and
      1/3 receiving the placebo formula. A skin care regimen of 3 products (serum,
      cream, and mask) containing alpha-defensin 5 and beta-defensin 3, and other
      cosmetic ingredients, was applied to the face, post-auricular, and neck skin two
      times per day for 12 weeks in those receiving full formula, whereas the placebo
      group received the identically packaged regimen without the active ingredients.
      Methods of evaluation included histopathology and immunohistochemistry (7
      subjects), clinical evaluation of pores, superficial and deep wrinkles based on
      Griffiths scale, and high-resolution photography (all subjects). In addition, a
      subset of 15 patients were evaluated with the QuantifiCare system (3-dimensional
      imaging and skin care scores for evenness, pores, oiliness) and Cortex
      measurements (high-resolution skin ultrasound, TEWL, elasticity, color, and
      hydration). Data points for evaluation included baseline, 6 weeks, and 12 weeks.
      All patients used the same sunscreen and cleanser, which was provided to them.
      RESULTS: The full formula regimen caused a significantly (P equals 0.027)
      increased thickness of the epidermis as seen in histology, not seen in the
      placebo group, with no signs of inflammation. No excessive cell proliferation was
      detected in either group as measured by Ki67-immunohistochemistry. Reduction in
      visible pores, superficial wrinkles, oiliness, pigmentation, and improvement of
      skin evenness, were statistically significant. A trend for improvement was also
      observed in skin elasticity, TEWL, and hydration; these did not achieve
      statistical significance. Ultrasound and histopathology demonstrated increases in
      dermal thickness in individual patients, without statistical significance.
      Comprehensive improvement in all 5 parameters, including visible pores,
      hyperpigmentation, superficial and deep wrinkles, and epidermal thickness, was
      statistically significant when the subset of participants assigned for histology
      in full formula group was compared with the placebo group participants.
      CONCLUSIONS: A 3-product skin care regimen containing alpha and beta defensins
      globally improves the visual appearance and structure of aging skin without
      irritation, dryness, or inflammation. Specifically, this regimen increases
      epidermal thickness, reduces appearance of pores, reduces wrinkles, and reduces
      melanin. This skin care regimen stimulates rejuvenation without evidence of
      increase of a marker of carcinogenic stimulation. This data is consistent with
      the hypothesis that a defensin-containing skin care regimen activates the body's
      own dormant stem cells to generate healthy new epidermal cells. <p><em>J Drugs
      Dermatol. 2018;17(4):426-441.</em></p> THIS ARTICLE HAD BEEN MADE AVAILABLE FREE
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PMID- 29601621
TI  - Prospective, Randomized, Investigator-Blinded, Split-Face Evaluation of a Topical
      Crosslinked Hyaluronic Acid Serum for Post-Procedural Improvement of Skin Quality
      and Biomechanical Attributes.
AB  - BACKGROUND: This split-face, controlled study investigated the ability of a
      topical crosslinked hyaluronic acid formulation (RHA serum) to enhance clinical
      results from fillers, microneedling, or chemical peeling of aging skin. Previous
      comparative skin explant studies demonstrated greater efficacy of RHA serum than
      topical non-crosslinked high or low molecular weight hyaluronic acid in
      decreasing trans-epidermal water loss, increasing epidermal hydration, and
      improving corneocyte microstructure. METHODS: 24 female subjects aged 35 to 55
      were enrolled. 8 received intradermal hyaluronic acid filler injection, 8
      received microneedling, and 8 received superficial mandelic acid chemical
      peeling. Subjects initiated twice-daily, standardized application of RHA serum to
      one side of the face 2 days after the procedure. Topographical imaging,
      bioinstrumental, and blinded clinical evaluations were performed at days 0, 14,
      and 28. RESULTS: Areas treated with RHA serum showed statistically significant
      improvements in skin surface topography and hydration compared to untreated
      areas. Blinded investigator scoring showed greater improvement of RHA serum
      treated skin in moisture, tone/complexion, radiance, texture, uniformity, and
      global appearance. Subjects' questionnaire responses correlated with these
      findings. Subjects expressed greater satisfaction with appearance of the treated
      hemiface. No adverse events were observed during the study. CONCLUSIONS: When
      initiated post-procedurally, topical RHA serum was well-tolerated and enhanced
      biomechanical properties, quality, and clinical appearance of the skin. Based on
      these data, RHA serum may be of value in improving patient outcomes and
      satisfaction following minimally invasive aesthetic procedures. The availability
      of the same hyaluronic acid technology also as a cohesive, tissue-integrating
      injectable filler enables synergistic, multi-level treatment plans to be devised.
      <p><em>J Drugs Dermatol. 2018;17(4):442-450.</em></p>.

PMID- 29601622
TI  - A Systematic Review of Topical Finasteride in the Treatment of Androgenetic
      Alopecia in Men and Women.
AB  - INTRODUCTION: Currently, only topical minoxidil (MNX) and oral finasteride (FNS)
      are approved by the Food and Drug Administration (FDA) and the European Medicines
      Agency (EMA) for the treatment of androgenetic alopecia. Although FNS is
      efficacious for hair regrowth, its systemic use is associated with side effects
      limiting long-term utilization. Exploring topical FNS as an alternative treatment
      regimen may prove promising. METHODS: A search was conducted to identify studies
      regarding human in vivo topical FNS treatment efficacy including clinically
      relevant case reports, randomized controlled trials (RCTs), and prospective
      studies. RESULTS: Seven articles were included in this systematic review. In all
      studies, there was significant decrease in the rate of hair loss, increase in
      total and terminal hair counts, and positive hair growth assessment with topical
      FNS. Both scalp and plasma DHT significantly decreased with application of
      topical FNS; no changes in serum testosterone were noted. CONCLUSION: Preliminary
      results on the use of topical FNS are limited, but safe and promising. Continued
      research into drug-delivery, ideal topical concentration and application
      frequency, side effects, and use for other alopecias will help to elucidate the
      full extent of topical FNS' use. <p><em>J Drugs Dermatol. 2018;17(4):457
      463.</em></p>.

PMID- 29601623
TI  - Dynamic Changes of Facial Supporting Cornerstones (Pillars): Considerations in
      Aesthetic Approach.
AB  - The bony structures of the face provide the framework upon which the soft-tissue
      envelope rests, such that facial symmetry and proportionality usually depend upon
      the morphological patterns and anthropometrical measurements of a symmetrical
      skull. Facial bony pillars are dynamic and variable according to the demands
      placed upon them, as well as gender and aging differences. Thus, a more profound
      knowledge of facial supporting pillars and their dynamic behavior by physicians
      who practice minimally cosmetic procedures would allow for a more natural
      approach to facial beautification. It would help them to rebalance age-related
      and asymmetric congenital imperfections, and minimize any harmful stigma
      associated with bad cosmetic practice. <p><em>J Drugs Dermatol. 2018;17(4):466
      470.</em></p>.

PMID- 29601624
TI  - Psoriasiform Pemphigus Foliaceus in an African American Female: An Important
      Clinical Manifestation.
AB  - A 50-year-old African-American woman presented to the dermatology clinic with a
      pruritic eruption of 3 years' duration. On clinical examination, the patient had
      well-demarcated, pink, atrophic plaques and superficial erosions over the
      inframammary folds and mid-chest. She also had well-demarcated, hyperpigmented,
      hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees,
      and back with sporadic small superficial blisters. A punch biopsy of the right
      abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal
      parakeratosis, and acantholysis throughout the superficial spinous and granular
      layers. Only a sparse inflammatory infiltrate was present in the underlying
      dermis. Clinical and histological findings supported the diagnosis of pemphigus
      foliaceus (PF), but psoriasis was included in the differential diagnosis due to
      the presence of discrete plaques with an erythematous border. We hypothesize that
      patients with psoriasiform presentations of PF may be misdiagnosed with plaque
      psoriasis. It is important to distinguish between PF and psoriasis as there is
      evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate
      PF. We document and highlight this atypical psoriasiform presentation of PF in a
      patient with skin of color to raise awareness and improve diagnosis and outcomes.
      <p><em>J Drugs Dermatol. 2018;17(4):471-473.</em></p>.

PMID- 29601625
TI  - Proximal Subungual Onychomycosis in the Immunocompetent: A Case Report and Review
      of the Literature.
AB  - Proximal subungual onychomycosis (PSO), which predominantly involves the nail
      plate from the proximal nail fold, is the rarest form of onychomycosis.
      Classically associated with an immunocompromised state, PSO is an uncommon
      diagnosis in individuals without immunodeficiency. We present a case of a healthy
      51-year-old man, who presented with a three-month history of white discoloration
      of multiple toenails. Physical examination revealed white, opaque patches on the
      proximal third nail plates of multiple toenails. The affected digits also
      demonstrated proximal onycholysis, subungual debris, and mild paronychia.
      Laboratory examinations, including routine serologic studies as well as human
      immunodeficiency virus and antinuclear antibodies, were within normal limits.
      Proximal nail fragments of the left hallux showed sections of dystrophic nail
      plate with mounds of parakeratosis, collections of neutrophils, and hyphae that
      highlighted with periodic acid-Schiff staining. The patient was diagnosed with
      PSO and tinea pedis bilaterally and treated with oral fluconazole with gradual
      improvement. This case of PSO highlights the potential for its rare occurrence in
      a healthy host. However, the clinical presentation of PSO should trigger an
      evaluation for possible immunodeficiency. <p><em>J Drugs Dermatol. 2018;17(4):475
      478.</em></p>.

PMID- 29601626
TI  - Successful Therapy of Severe Oro-Labial Herpes Simplex With Muco-Adhesive
      Acyclovir.
AB  - Although muco-adhesive acyclovir 50mg tablets are only approved for the
      management of recurrent oro-labial HSV-1 infections, their ability to achieve
      extremely high concentrations in saliva and oral tissues suggests the potential
      for other uses. In this case, the agent was successfully utilized as a single
      tablet monotherapy leading to rapid clinical resolution of severe post-operative
      oro-labial infection. <p><em>J Drugs Dermatol. 2018;17(4):479-480.</em></p>.

PMID- 29601627
TI  - Dermatology on Instagram: An Analysis of Hashtags.
AB  - Forty-two percent of Americans search for health-related information on social
      media platforms, and forty-five percent of consumers report that social media
      health information influences their decision to seek care.

PMID- 29601628
TI  - Controversy: Mohs and Close.
AB  - .

PMID- 29601629
TI  - Skin Type Classification: A Decennial Perspective.
AB  - The intent of this brief communication is to revisit the Roberts Skin Type
      Classification System published by Journal of Drugs in Dermatology (JDD) in 2008
      with a 2018 lens and provide additional information for its wider acceptance and
      implementation.

PMID- 29601630
TI  - Overcoming Challenges to US Payment Reform: Could a Place-Based Approach Help?

PMID- 29601631
TI  - A Preliminary Analysis of the Age of Full Expression of Sexually Dimorphic
      Cranial Traits.
AB  - Although high accuracy rates have been achieved for adult skeletal sex
      estimation, it is unclear at what age sexually dimorphic traits of the skull
      become fully developed and useful in subadults. Four linear distances that
      capture sexual dimorphism-the nuchal crest, mastoid process, glabella, and mental
      eminence-were measured in a longitudinal sample of lateral cranial radiographs
      from 10 males and 10 females in the Denver Growth Study (total n = 190). The age
      full trait expression was attained was compared to that of dental maturity (i.e.,
      third molar eruption). The mental eminence reached full expression significantly
      earlier than dental maturity (p < 0.001), although a high degree of variability
      was observed. Ages of expression of the other traits did not differ significantly
      from dental maturity. These results suggest that in forensic cases, where
      misclassification can have substantial impacts, cranial traits cannot yet be used
      reliably for sex estimation prior to third molar eruption.

PMID- 29601632
TI  - Green leaf volatiles protect maize (Zea mays) seedlings against damage from cold
      stress.
AB  - Although considerable evidence has accumulated on the defensive activity of plant
      volatile organic compounds against pathogens and insect herbivores, less is known
      about the significance of volatile organic compounds emitted by plants under
      abiotic stress. Here, we report that green leaf volatiles (GLVs), which were
      previously shown to prime plant defences against insect herbivore attack, also
      protect plants against cold stress (4  degrees C). We show that the expression
      levels of several cold stress-related genes are significantly up-regulated in
      maize (Zea mays) seedlings treated with physiological concentrations of the GLV,
      (Z)-3-hexen-1-yl acetate (Z-3-HAC), and that seedlings primed with Z-3-HAC
      exhibit increased growth and reduced damage after cold stress relative to
      unprimed seedlings. Together, these data demonstrate the protective and priming
      effect of GLVs against cold stress and suggest an activity of GLVs beyond the
      activation of typical plant defence responses against herbivores and pathogens.

PMID- 29601633
TI  - Programmed death-ligand 1 (PD-L1) expression in pleomorphic carcinoma of the
      lung.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary pleomorphic carcinoma (PPC) is a rare and
      aggressive subtype of lung cancer. Programmed cell death-ligand 1 (PD-L1)
      expression may be induced in a variety of malignant tumors, but its prognostic
      implication in PPC remains unclear. METHODS: Twenty-six patients with surgically
      resected PPC were retrospectively reviewed. Immuno-histochemical staining was
      used to detect PD-L1 expression, and PD-L1 status was classified into "high" or
      "low" according to the percentage of tumor cells (TCs) expressing PD-L1 (tumor
      proportion score, TPS). RESULTS: PD-L1 expression was positive in 20 (76.9%)
      patients at the cut-off TPS value of 1%. A receiver-operating characteristic
      (ROC) analysis showed that the optimal cut-off value was 15% for prediction of
      cancer-specific death with the area under ROC curve of 0.701 (P = 0.107). High PD
      L1 expression was associated with a favorable overall survival (100% vs 45.9% at
      5 years; P = 0.046) as well as a favorable cancer-specific survival (88.9% vs
      37.5% at 5 years; P = 0.012). A multivariate analysis indicated a trend toward a
      favorable prognosis associated with high PD-L1 expression (hazard ratio [HR],
      0.254 [95% confidence interval, 0.054-1.200]; P = 0.084). CONCLUSIONS: PD-L1
      expression was positive in most PPC cases, and high PD-L1 expression may predict
      a favorable prognosis in resected PPC.

PMID- 29601634
TI  - Intraoperative identification and definition of "functional" lymphatic collecting
      vessels for supermicrosurgical lymphatico-venous anastomosis in treating
      lymphedema patients.
AB  - BACKGROUND: For current lymphatico-venous anastomosis (LVA), the identification
      of "functional" lymphatic collecting vessels (LCVs) is mainly based on
      indocyanine green (ICG) lymphography. However, some of the non-ICG enhanced LCVs
      utilized for LVA were found to have visual lymphatic flow. OBJECTIVES: Should non
      ICG enhanced, but flow-positive LCVs be considered functional as well? METHODS: A
      retrospective study with 56 consecutive lymphedema patients (8 male/48 female)
      received LVA. LCVs were observed after ICG injection, before/after LVAs were
      performed. ICG enhancement and lymphatic flow in the LCVs were recorded and
      grouped as: Group A: all LCVs ICG(+) and flow(+); Group B: all LCVs ICG(+) and
      some were flow(+); Group C: some ICG(+) and some flow(+) LCVs; Group D: all LCVs
      ICG(-)but all flow(+); and Group E: all LCVs were both ICG(-) and flow(-).
      RESULTS: A total of 366 LCVs were identified, averaging 8.2 LVAs, 6.5 LCVs, and
      4.7 veins per patient. A total of 33 LVAs were performed with 27 LCVs with no ICG
      enhancement from 7 patients (Group D). These patients were satisfied with their
      lymphedema improvements. CONCLUSION: Lymphatic flow-positive but non-ICG enhanced
      LCVs, should also be considered as functional, thereby maximizing the number of
      functional LCVs for LVA.

PMID- 29601635
TI  - Fatal Poisoning with Both Dichlorvos and Phenthoate.
AB  - Organophosphates are widely used as pesticides. However, organophosphates are
      occasionally orally ingested to commit suicide. In this case, a man in his late
      80s committed suicide by ingesting both dichlorvos and phenthoate. Autopsy
      findings revealed a characteristic volatile odor from his mouth, stomach, lungs,
      liver, and kidneys. The esophageal mucosa was denatured and had lost elasticity.
      Serum cholinesterase activity was 9 IU/L. Toxicological analyses performed using
      high-performance liquid chromatography-tandem mass spectrometry revealed that
      dichlorvos concentrations in the left and right cardiac blood samples were 11.6
      and 4.6 MUg/mL, respectively. Phenthoate concentrations in the left and right
      cardiac blood samples were 5.8 and 0.51 MUg/mL, respectively. The total amounts
      of dichlorvos and phenthoate in the stomach were 7.35 and 4.55 g, respectively.
      The case history, autopsy findings, and toxicological analyses indicated that the
      cause of death was acute fatal poisoning after oral ingestion of both dichlorvos
      and phenthoate.

PMID- 29601636
TI  - Mean residual life regression with functional principal component analysis on
      longitudinal data for dynamic prediction.
AB  - Predicting patient life expectancy is of great importance for clinicians in
      making treatment decisions. This prediction needs to be conducted in a dynamic
      manner, based on longitudinal biomarkers repeatedly measured during the patient's
      post-treatment follow-up period. The prediction is updated any time a new
      biomarker measurement is obtained. The heterogeneity across patients of biomarker
      trajectories over time requires flexible and powerful approaches to model noisy
      and irregularly measured longitudinal data. In this article, we use functional
      principal component analysis (FPCA) to extract the dominant features of the
      biomarker trajectory of each individual, and use these features as time-dependent
      predictors (covariates) in a transformed mean residual life (MRL) regression
      model to conduct dynamic prediction. Simulation studies demonstrate the improved
      performance of the transformed MRL model that includes longitudinal biomarker
      information in the prediction. We apply the proposed method to predict the
      remaining time expectancy until disease progression for patients with chronic
      myeloid leukemia, using the transcript levels of an oncogene, BCR-ABL.

PMID- 29601638
TI  - Undiagnosed Congenital Heart Defects as a Cause of Sudden, Unexpected Death in
      Children.
AB  - Despite advances in the diagnosis and treatment of congenital heart defects
      (CHDs), these defects are still an important cause of sudden, unexpected death in
      young children. This retrospective study identified 64 cases of CHDs presenting
      as a cause of sudden, unexpected death in a busy, urban Medical Examiner's Office
      pediatric population between 2006 and 2016. The majority of cases (52 of 64, 81%)
      were infants. Interestingly, 52% of cases were undiagnosed prior to autopsy.
      Ventricular septal defects and atrioventricular septal defects were the most
      common simple (14%) and complex (17%) malformations observed, respectively. In
      many cases, there were coexistent simple and/or complex defects. Most of the
      cases diagnosed with CHD prior to autopsy (48%) had undergone some type of
      surgical repair. This study highlights the importance of considering undiagnosed
      CHDs as a cause of sudden, unexpected death, particularly in young children.

PMID- 29601637
TI  - Using dynamic clamp to quantify pathological changes in the excitability of
      primary somatosensory neurons.
AB  - KEY POINTS: Primary somatosensory neurons normally respond to somatic
      depolarization with transient spiking but can switch to repetitive spiking under
      pathological conditions. This switch in spiking pattern reflects a qualitative
      change in spike initiation dynamics and contributes to the hyperexcitability
      associated with chronic pain. Neurons can be converted to repetitive spiking by
      adding a virtual conductance using dynamic clamp. By titrating the conductance to
      determine how much must be added to cause repetitive spiking, we found that small
      cells are more susceptible to switching (i.e. required less added conductance)
      than medium-large cells. By measuring how much less conductance is required to
      cause repetitive spiking when dynamic clamp was combined with other pathomimetic
      manipulations (e.g. application of inflammatory mediators), we measured how much
      each manipulation facilitated repetitive spiking. Our results suggest that many
      pathological factors facilitate repetitive spiking but that the switch to
      repetitive spiking requires the cumulative effect of many co-occurring factors.
      ABSTRACT: Primary somatosensory neurons become hyperexcitable in many chronic
      pain conditions. Hyperexcitability can include a switch from transient to
      repetitive spiking during sustained somatic depolarization. This switch results
      from diverse pathological processes that impact ion channel expression or
      function. Because multiple pathological processes co-occur, isolating how much
      each contributes to switching the spiking pattern is difficult. Our approach to
      this challenge involves adding a virtual sodium conductance via dynamic clamp.
      The magnitude of that conductance was titrated to determine the minimum required
      to enable rheobasic stimulation to evoke repetitive spiking. The minimum required
      conductance, termed g- Na *, was re-measured before and during manipulations
      designed to model various pathological processes in vitro. The reduction in g- Na
      * caused by each pathomimetic manipulation reflects how much the modelled process
      contributes to switching the spiking pattern. We found that elevating
      extracellular potassium or applying inflammatory mediators reduced g- Na *
      whereas direct hyperpolarization had no effect. Inflammatory mediators reduced g-
      Na * more in medium-large (>30 MUm diameter) neurons than in small (?30 MUm
      diameter) neurons, but had equivalent effects in cutaneous and muscle afferents.
      The repetitive spiking induced by dynamic clamp was also found to differ between
      small and medium-large neurons, thus revealing latent differences in adaptation.
      Our study demonstrates a novel way to determine to what extent individual
      pathological factors facilitate repetitive spiking. Our results suggest that most
      factors facilitate but do not cause repetitive spiking on their own, and,
      therefore, that a switch to repetitive spiking results from the cumulative effect
      of many co-occurring factors.

PMID- 29601639
TI  - Optimization of Sample Preparation processes of Bone Material for Raman
      Spectroscopy.
AB  - Raman spectroscopy has recently been investigated for use in the calculation of
      postmortem interval from skeletal material. The fluorescence generated by
      samples, which affects the interpretation of Raman data, is a major limitation.
      This study compares the effectiveness of two sample preparation techniques,
      chemical bleaching and scraping, in the reduction of fluorescence from bone
      samples during testing with Raman spectroscopy. Visual assessment of Raman
      spectra obtained at 1064 nm excitation following the preparation protocols
      indicates an overall reduction in fluorescence. Results demonstrate that scraping
      is more effective at resolving fluorescence than chemical bleaching. The scraping
      of skeletonized remains prior to Raman analysis is a less destructive method and
      allows for the preservation of a bone sample in a state closest to its original
      form, which is beneficial in forensic investigations. It is recommended that bone
      scraping supersedes chemical bleaching as the preferred method for sample
      preparation prior to Raman spectroscopy.

PMID- 29601640
TI  - Breast cancer subtypes and local recurrence rate after surgery for bone
      metastasis to the extremities.

PMID- 29601641
TI  - Testing cross-phenotype effects of rare variants in longitudinal studies of
      complex traits.
AB  - Many gene mapping studies of complex traits have identified genes or variants
      that influence multiple phenotypes. With the advent of next-generation sequencing
      technology, there has been substantial interest in identifying rare variants in
      genes that possess cross-phenotype effects. In the presence of such effects,
      modeling both the phenotypes and rare variants collectively using multivariate
      models can achieve higher statistical power compared to univariate methods that
      either model each phenotype separately or perform separate tests for each
      variant. Several studies collect phenotypic data over time and using such
      longitudinal data can further increase the power to detect genetic associations.
      Although rare-variant approaches exist for testing cross-phenotype effects at a
      single time point, there is no analogous method for performing such analyses
      using longitudinal outcomes. In order to fill this important gap, we propose an
      extension of Gene Association with Multiple Traits (GAMuT) test, a method for
      cross-phenotype analysis of rare variants using a framework based on the distance
      covariance. The approach allows for both binary and continuous phenotypes and can
      also adjust for covariates. Our simple adjustment to the GAMuT test allows it to
      handle longitudinal data and to gain power by exploiting temporal correlation.
      The approach is computationally efficient and applicable on a genome-wide scale
      due to the use of a closed-form test whose significance can be evaluated
      analytically. We use simulated data to demonstrate that our method has favorable
      power over competing approaches and also apply our approach to exome chip data
      from the Genetic Epidemiology Network of Arteriopathy.

PMID- 29601642
TI  - The plastoquinone pool outside the thylakoid membrane serves in plant
      photoprotection as a reservoir of singlet oxygen scavengers.
AB  - The Arabidopsis vte1 mutant is devoid of tocopherol and plastochromanol (PC-8).
      When exposed to excess light energy, vte1 produced more singlet oxygen (1 O2 )
      and suffered from extensive oxidative damage compared with the wild type. Here,
      we show that overexpressing the solanesyl diphosphate synthase 1 (SPS1) gene in
      vte1 induced a marked accumulation of total plastoquinone (PQ-9) and rendered the
      vte1 SPS1oex plants tolerant to photooxidative stress, indicating that PQ-9 can
      replace tocopherol and PC-8 in photoprotection. High total PQ-9 levels were
      associated with a noticeable decrease in 1 O2 production and higher levels of
      Hydroxyplastoquinone (PQ-C), a 1 O2 -specific PQ-9 oxidation product. The extra
      PQ-9 molecules in the vte1 SPS1oex plants were stored in the plastoglobules and
      the chloroplast envelopes, rather than in the thylakoid membranes, whereas PQ-C
      was found almost exclusively in the thylakoid membranes. Upon exposure of wild
      type plants to high light, the thylakoid PQ-9 pool decreased, whereas the
      extrathylakoid pool remained unchanged. In vte1 and vte1 SPS1oex plants, the PQ-9
      losses in high light were strongly amplified, affecting also the extrathylakoid
      pool, and PQ-C was found in high amounts in the thylakoids. We conclude that the
      thylakoid PQ-9 pool acts as a 1 O2 scavenger and is replenished from the
      extrathylakoid stock.

PMID- 29601643
TI  - An Integrated Scenario Ensemble-Based Framework for Hurricane Evacuation
      Modeling: Part 1-Decision Support System.
AB  - This article introduces a new integrated scenario-based evacuation (ISE)
      framework to support hurricane evacuation decision making. It explicitly captures
      the dynamics, uncertainty, and human-natural system interactions that are
      fundamental to the challenge of hurricane evacuation, but have not been fully
      captured in previous formal evacuation models. The hazard is represented with an
      ensemble of probabilistic scenarios, population behavior with a dynamic decision
      model, and traffic with a dynamic user equilibrium model. The components are
      integrated in a multistage stochastic programming model that minimizes risk and
      travel times to provide a tree of evacuation order recommendations and an
      evaluation of the risk and travel time performance for that solution. The ISE
      framework recommendations offer an advance in the state of the art because they:
      (1) are based on an integrated hazard assessment (designed to ultimately include
      inland flooding), (2) explicitly balance the sometimes competing objectives of
      minimizing risk and minimizing travel time, (3) offer a well-hedged solution that
      is robust under the range of ways the hurricane might evolve, and (4) leverage
      the substantial value of increasing information (or decreasing degree of
      uncertainty) over the course of a hurricane event. A case study for Hurricane
      Isabel (2003) in eastern North Carolina is presented to demonstrate how the
      framework is applied, the type of results it can provide, and how it compares to
      available methods of a single scenario deterministic analysis and a two-stage
      stochastic program.

PMID- 29601644
TI  - Review article: nonclinical and clinical pharmacology, pharmacokinetics and
      pharmacodynamics of etrolizumab, an anti-beta7 integrin therapy for inflammatory
      bowel disease.
AB  - BACKGROUND: Novel treatments with superior benefit-risk profiles are needed to
      improve the long-term prognosis of patients with inflammatory bowel disease
      (IBD). Etrolizumab-a monoclonal antibody that specifically targets beta7
      integrins-is currently under phase III clinical evaluation in IBD. AIM: This
      review summarises the available pharmacological and
      pharmacokinetic/pharmacodynamic data for etrolizumab to provide a comprehensive
      understanding of its mechanism of action (MOA) and pharmacological effects.
      METHODS: Published and internal unpublished data from nonclinical and clinical
      studies with etrolizumab are reviewed. RESULTS: Etrolizumab exerts its effect via
      a unique dual MOA that inhibits both leucocyte trafficking to the intestinal
      mucosa and retention within the intestinal epithelial layer. The gut-selectivity
      of etrolizumab results from its specific targeting of the beta7 subunit of
      alpha4beta7 and alphaEbeta7 integrins. Etrolizumab does not bind to alpha4beta1
      integrin, which mediates lymphocyte trafficking to tissues including the central
      nervous system, a characteristic underlying its favourable safety with regard to
      progressive multifocal leucoencephalopathy. Phase I/II studies in patients with
      ulcerative colitis (UC) showed linear pharmacokinetics when etrolizumab was
      administered subcutaneously at 100 mg or higher once every 4 weeks. This dose was
      sufficient to enable full beta7 receptor occupancy in both blood and intestinal
      tissues of patients with moderate to severe UC. The phase II study results also
      suggested that patients with elevated intestinal expression of alphaE integrin
      may have an increased likelihood of clinical remission in response to etrolizumab
      treatment. CONCLUSION: Etrolizumab is a gut-selective, anti-beta7 integrin
      monoclonal antibody that may have therapeutic potential for the treatment of IBD.

PMID- 29601645
TI  - Testing the effects of explicit and implicit bidimensional attitudes on
      objectively measured speeding behaviour.
AB  - Bidimensional attitudes have been shown to independently predict behaviour, with
      the positive dimension of attitude being a stronger predictor of behaviour than
      the negative dimension (e.g., Elliott, Brewster, et al., 2015, Br. J. Psychol,
      106, 656). However, this positivity bias has been demonstrated with explicit
      attitude measures only and explicit attitude measures tap deliberative processes
      rather than automatic processes, which are known to be important in the execution
      of many behaviours. The aim of this study was to test whether implicit
      bidimensional attitudes can account for variance in speeding behaviour over and
      above explicit bidimensional attitudes and whether the positivity bias that is
      typically found with explicit attitudes generalizes to implicit attitudes. A
      total of 131 drivers completed a questionnaire measuring their explicit
      bidimensional attitudes towards speeding. They also completed Implicit
      Association Tests measuring their implicit bidimensional attitudes. Two weeks
      later, speeding behaviour was measured using a driving simulator. Explicit
      attitudes accounted for a significant proportion of the variance in subsequent
      speeding behaviour. Implicit attitudes accounted for a statistically significant
      increment to explained variance. The positive dimension of both explicit and
      implicit attitudes predicted speeding behaviour but the negative dimensions did
      not. Theoretical implications for understanding the potential attitudinal causes
      of behaviour and practical implications for behaviour-change interventions are
      discussed.

PMID- 29601646
TI  - Enantioseparation of (RS)-fexofenadine and enhanced detection as the
      diastereomeric amide and anhydride derivatives using liquid chromatography-mass
      spectrometry.
AB  - Enantioselective analysis of (RS)-fexofenadine was carried out by achiral HPLC
      via a derivatization approach using N-hydroxy-benzotriazolyl-(S)-naproxen ester
      (synthesized for this purpose) and three chirally pure amines as chiral
      derivatizing reagents. There occurred formation of amide and anhydride types of
      diastereomeric derivatives. These were separated and isolated by HPLC (analytical
      and preparative). The structures and configurations were verified via recording
      full-scan product ion mass spectra using LC-MS, 1 HNMR spectra, Chem3D Pro 12.0
      software and the software Gaussian 09 Rev.A.02 program and hybrid density
      functional B3LYP with 6-31G basis set supplemented with polarimetry. Experimental
      conditions for synthesis and separations were optimized and the elution order was
      established. Analytical separation was performed on a C18 analytical column with
      different ratios of MeCN-TEAP buffer and MeOH-TEAP buffer (v/v) adjusted to pH
      7.5 as mobile phase at a flow rate of 0.7 mL min-1 . Detection was performed via
      UV absorbance at 225 nm. The method was validated in accordance with
      International Conference on Harmonization guidelines. The detection limits were
      6.25 and 7.87 ng mL-1 for first and second eluting diastereomeric derivatives,
      respectively.

PMID- 29601647
TI  - Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075
      patients with chronic HBV infection.
AB  - BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis
      in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index
      stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment
      naive, noncirrhotic the patients with chronic HBV infection were included. Most
      of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were
      explored to stratify the risks of cirrhosis, cirrhosis-related complications and
      liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years,
      we found a higher baseline FIB-4 index was associated with increased incidence
      rates of cirrhosis in addition to the common host and viral factors. Patients
      with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with
      increased risks of cirrhosis, cirrhosis-related complications and liver-related
      mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05),
      6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years
      of follow-up, FIB-4 remained stable and its kinetics were consistently associated
      with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29
      was able to stratify all the risks of adverse liver events even in HBeAg-negative
      patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000
      IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis
      but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic
      patients with chronic HBV infection, a higher FIB-4 index was associated with
      increased risks of adverse liver events. FIB-4 index <1.29 is useful for the
      prediction of the lowest risks of disease progression.

PMID- 29601648
TI  - In response to: Long-term overall survival of patients diagnosed with pure
      tubular carcinoma of the breast might be affected by increased co-morbidities.

PMID- 29601649
TI  - Long-term overall survival of patients diagnosed with pure tubular carcinoma of
      the breast might be affected by increased co-morbidities.

PMID- 29601650
TI  - Prior knowledge of category size impacts visual search.
AB  - Prior research has shown that category search can be similar to one-item search
      (as measured by the N2pc ERP marker of attentional selection) for highly
      familiar, smaller categories (e.g., letters and numbers) because the finite set
      of items in a category can be grouped into one unit to guide search. Other
      studies have shown that larger, more broadly defined categories (e.g., healthy
      food) also can elicit N2pc components during category search, but the amplitude
      of these components is typically attenuated. Two experiments investigated whether
      the perceived size of a familiar category impacts category and exemplar search.
      We presented participants with 16 familiar company logos: 8 from a smaller
      category (social media companies) and 8 from a larger category
      (entertainment/recreation manufacturing companies). The ERP results from
      Experiment 1 revealed that, in a two-item search array, search was more efficient
      for the smaller category of logos compared to the larger category. In a four-item
      search array (Experiment 2), where two of the four items were placeholders,
      search was largely similar between the category types, but there was more
      attentional capture by nontarget members from the same category as the target for
      smaller rather than larger categories. These results support a growing literature
      on how prior knowledge of categories affects attentional selection and capture
      during visual search. We discuss the implications of these findings in relation
      to assessing cognitive abilities across the lifespan, given that prior knowledge
      typically increases with age.

PMID- 29601651
TI  - Calpain-2 triggers prostate cancer metastasis via enhancing CRMP4 promoter
      methylation through NF-kappaB/DNMT1 signaling pathway.
AB  - BACKGROUND: Metastasis is the major cause of cancer-specific death in patients
      with prostate cancer (PCa). We previously reported that collapsing response
      mediator protein-4 (CRMP4) is a PCa metastasis-suppressor gene and the
      hypermethylation in CRMP4 promoter is responsible for the transcription
      repression in metastatic PCa. However, the underlying mechanisms remain unknown.
      In this study, we aimed to investigate the role of calpain-2 in CRMP4 promoter
      hypermethylation and its functional modulation in PCa metastasis. METHODS:
      Calpain-2 expression in PCa tissues (n = 87) and its specific mechanisms of
      functional modulation in CRMP4 expression via limited enzymatic cleavage was
      investigated. We then focused on the cooperative crosstalk of calpain-2 and NF
      kappaB RelA/p65 in CRMP4 promoter methylation for the initiation of PCa
      metastasis. Statistical differences between groups were determined using a two
      tailed Student's t-test. P < 0.05 indicated statistically significant. RESULTS:
      Calpain-2 was differentially upregulated in metastatic PCa compared with
      localized PCa. Moreover, calpain-2 cleaved CRMP4 into the N-terminally fragment
      which promoted migration and invasion in PCa cells via nuclear translocation and
      activation of E2F1-mediated DNA methyltransferase 1 (DNMT1) expression. NF-kappaB
      RelA/p65 recruited DNMT1 to bind to and methylate CRMP4 promoter in which
      Serine276 phosphorylation of p65 was essential. Furthermore, CRMP4 exhibited anti
      metastatic function via inhibiting the expression of VEGFC through Semaphorin3B
      Neuropilin2 signaling. CONCLUSION: Calpain-2 may contribute to the promoter
      methylation of CRMP4 to repress its transcription, leading to the metastasis of
      PCa via enhancing VEGFC expression.

PMID- 29601652
TI  - Comparison of clinical outcomes between variceal and non-variceal
      gastrointestinal bleeding in patients with cirrhosis.
AB  - BACKGROUND AND AIM: Acute upper gastrointestinal bleeding (UGIB) in cirrhosis is
      associated with significant morbidity and mortality and can be classified as
      acute variceal bleeding (AVB) or non-variceal bleeding (NVB). Differences in
      mortality, hospital length of stay (LOS), and 30-day readmission have yet to be
      determined. As such, the study aimed to evaluate differences in these clinical
      outcomes in cirrhotic patients admitted with UGIB. METHODS: This retrospective
      study included all cirrhotic patients hospitalized for UGIB who underwent upper
      endoscopy from July 2014 to July 2016. AVB was defined as the presence of varices
      on endoscopy with high-risk stigmata such as cherry-red spots. Mortality,
      intensive care unit admission, hospital LOS, and 30-day hospital readmission were
      recorded and compared among patients with AVB and NVB. RESULTS: A total of 116
      patients with cirrhosis were included, 73 with AVB and 43 with NVB. Patients with
      NVB were older than those with AVB (60.4 +/- 11.1 vs 55.0 +/- 9.5, P = 0.006)
      whereas patients with AVB were more likely to have known esophageal varices
      (64.4% vs 37.2%, P = 0.007). Patients with AVB and NVB had similar mortality
      (15.1% vs 9.3%, P = 0.57), hospital LOS (4.9, interquartile range: 3.6-6.9 days
      vs 5.0, interquartile range: 2.7-8.3 days), and 30-day readmission rates (19.2%
      vs 30.2%, P = 0.18). Severity of clinical presentation was associated with
      increased LOS and overall mortality, including the need for intensive care unit
      admission, but these were not associated with 30-day readmission rates.
      CONCLUSION: There were no differences in clinical outcomes, including mortality,
      in cirrhotic patients admitted with AVB and NVB.

PMID- 29601653
TI  - Angiostrongylosis in dogs with negative fecal and in-clinic rapid serological
      tests: 7 Cases (2013-2017).
AB  - BACKGROUND: Angiostrongylosis is considered as emerging disease in dogs in
      Belgium. Detection of first-stage larvae in feces using the Baermann method has
      an imperfect sensitivity. OBJECTIVES: Investigation of efficacy of noninvasive
      blood and fecal diagnostic tests in comparison with PCR on bronchoalveolar lavage
      (BAL) material in a small series of coughing or dyspnoeic dogs naturally infected
      with Angiostrongylus vasorum. ANIMALS: Seven dogs with angiostrongylosis.
      METHODS: Retrospective study. Dogs with cough, exercise intolerance and dyspnea
      of 2- to 8-week duration. Diagnostic methods used included Baermann analysis,
      AngioDetect rapid assay, ELISAs for detection of circulating antigen and specific
      antibodies and qPCR on BAL material. RESULTS: Baermann analysis, AngioDetect
      rapid assay, antigen ELISA, antibody ELISA, and qPCR on BAL material were
      positive in 3/7, 2/7, 3/6, 6/6, and 7/7 dogs, respectively. ELISA for antibodies
      or qPCR on BAL material were essential for definitive diagnosis in 3 dogs.
      Relative sensitivities of AngioDetect rapid assay, Baermann analysis, and ELISA
      for antigen detection were lower than 50% compared with ELISA for antibodies or
      qPCR on BAL material. CONCLUSION AND CLINICAL IMPORTANCE: In this small clinical
      series, Baermann analysis and AngioDetect rapid assay failed to confirm the
      diagnosis in some dogs. Therefore, ELISA for antibody detection and qPCR on BAL
      material should strongly be considered in clinically suspected dogs when antigen
      detection methods (AngioDetect or ELISA) and Baermann analysis are negative.

PMID- 29601654
TI  - Predictors of anxiety and depression 2 years following treatment in uveal
      melanoma survivors.
AB  - OBJECTIVE: We examined the role of posttreatment symptoms and functional problems
      and of worry about recurrent disease (WREC) in predicting probable anxiety and
      depression cases 24 months after diagnosis in survivors of posterior uveal
      melanoma. We examined whether WREC mediates links between symptoms, functional
      problems, and probable anxiety and depression cases. METHODS: Prospective cohort
      study of 261 treated uveal melanoma survivors 6, 12, and 24 months after
      diagnosis. Hierarchical logistic regression analyses predicting anxiety and
      depression 24 months after diagnosis identified by Hospital Anxiety and
      Depression Scale cutoff scores. Symptoms, functional problems, and WREC 6-month
      posttreatment were entered into the analyses as predictors, then the same
      variables at 12 months. We controlled anxiety or depression at 6 and 12 months
      and chromosome 3 status, which accurately predicts 10-year survival. Mediation of
      links between 6-month symptoms and functional problems and 24-month anxiety and
      depression by 12-month WREC was tested. RESULTS: Anxiety caseness at 24 months
      was predicted by 6-month ocular irritation, headache, and functional problems and
      12-month WREC. Depression caseness at 24 months was predicted by 6-month headache
      and functional problems. Worry about recurrent disease at 12 months mediated
      prediction of anxiety caseness by 6-month symptoms and functional problems.
      Chromosome 3 status predicted neither anxiety nor depression. CONCLUSIONS:
      Survivors reporting symptoms, functional problems, and WREC should be monitored
      for anxiety and depression. Appropriate reassurance that symptoms do not signify
      future disease might help prevent anxiety.

PMID- 29601655
TI  - Translucent windows: how uncertainty in competitive interactions impacts
      detection of community pattern.
AB  - Traits can provide a window into the mechanisms that maintain coexistence among
      competing species. Recent theory suggests that competitive interactions will lead
      to groups, or clusters, of species with similar traits. However, theoretical
      predictions typically assume complete knowledge of the map between competition
      and measured traits. These assumptions limit the plausible application of these
      patterns for inferring competitive interactions in nature. Here, we relax these
      restrictions and find that the clustering pattern is robust to contributions of
      unknown or unobserved niche axes. However, it may not be visible unless measured
      traits are close proxies for niche strategies. We conclude that patterns along
      single niche axes may reveal properties of interspecific competition in nature,
      but detecting these patterns requires natural history expertise firmly tying
      traits to niches.

PMID- 29601656
TI  - A Multicontrolled Enamine Configurational Switch Undergoing Dynamic
      Constitutional Exchange.
AB  - A multiresponsive enamine-based molecular switch is presented, in which
      forward/backward configurational rotation around the C=C bond could be precisely
      controlled by the addition of an acid/base or metal ions. Fluorescence turn
      on/off effects and large Stokes shifts were observed while regulating the
      switching process with CuII . The enamine functionality furthermore enabled
      double dynamic regimes, in which configurational switching could operate in
      conjunction with constitutional enamine exchange of the rotor part. This behavior
      was used to construct a prototypical dynamic covalent switch system through
      enamine exchange with primary amines. The dynamic exchange process could be
      readily turned on/off by regulating the switch status with pH.

PMID- 29601657
TI  - Health care costs of depression in patients diagnosed with cancer.
AB  - OBJECTIVE: Depression is common among patients diagnosed with cancer. Patients
      with cancer and depression use more health care services compared with
      nondepressed cancer patients. The current study seeks to estimate the added cost
      of depression in cancer patients in the first year after cancer diagnosis.
      METHODS: Health care charges were obtained for 2051 depressed and 11 182
      nondepressed patients with an International Classification of Diseases, Ninth
      Revision, diagnosis of cancer in the 2014 calendar year from the University of
      California San Diego Healthcare System. The annual health care charges for cancer
      patients with and without depression were analyzed using generalized linear
      models with a log-link function and gamma distribution, covarying for age, sex,
      race/ethnicity, comorbid diseases, and presence of metastatic disease. Total cost
      data were broken down into several categories including ambulatory care,
      emergency department visits, and hospital visits. RESULTS: Depressed cancer
      patients had total annual health care charges that were 113% higher than
      nondepressed cancer patients (B = 0.76; P < .001). The estimated mean charges for
      depressed patients were $235 337 compared with $110 650 for nondepressed
      patients. Depressed cancer patients incurred greater charges than nondepressed
      patients in ambulatory care (B = 0.70; P < .001), emergency department charges (B
      = 0.31; P < .001), and hospital charges (B = 0.39; P < .001). CONCLUSIONS:
      Depressed cancer patients incur significantly higher health care charges across
      multiple cost categories including ambulatory care, emergency department visits,
      and hospital visits. Future research should investigate if interventions for
      detecting and treating depression are effective for reducing health care use and
      costs in cancer patients.

PMID- 29601658
TI  - Chromatographic characterisation of 11 phytocannabinoids: Quantitative and fit-to
      purpose performance as a function of extra-column variance.
AB  - INTRODUCTION: Cannabis sativa L. (cannabis) is utilised as a therapeutic and
      recreational drug. With the legalisation of cannabis in many countries and the
      anticipated regulation of potency that will accompany legalisation, analytical
      testing facilities will require a broadly applicable, quantitative, high
      throughput method to meet increased demand. Current analytical methods for the
      biologically active components of cannabis (phytocannabinoids) suffer from low
      throughput and/or an incomplete complement of relevant phytocannabinoids.
      OBJECTIVE: To develop a rapid, quantitative and broadly applicable liquid
      chromatography-tandem mass spectrometry analytical method for 11
      phytocannabinoids in cannabis with acidic and neutral character. METHODOLOGY:
      Bulk diffusion coefficients were calculated using the Taylor-Aris open tubular
      method, with four reference compounds used to validate the experimental set-up.
      Three columns were quantitatively evaluated using van Deemter plots and fit-to
      purpose performance metrics. Low (1.2 MUL2 ) and standard (3.6 MUL2 ) extra
      column variance ultra-high pressure liquid chromatography (UPLC) configurations
      were contrasted. Method performance was demonstrated with methanolic cannabis
      flower extracts. RESULTS: Bulk diffusion coefficients and van Deemter plots for
      11 phytocannabinoids are reported. The developed chromatographic method includes
      the challenging Delta8 /Delta9 -tetrahydrocannabinol isobars and, at 6.5 min, is
      faster than existing methods targeting similar panels of biologically active
      phytocannabinoids. CONCLUSIONS: The bulk diffusion coefficients and van Deemter
      curves informed the development of a rapid quantitative method and will
      facilitate potential expansion to include additional compounds, including
      synthetic cannabinoids. The developed method can be implemented with low or
      standard extra-column variance UPLC configurations.

PMID- 29601659
TI  - Promoting active ageing in older people with mental disorders living in the
      community: An integrative review.
AB  - AIM: To critically synthesize the evidence in relation to the promotion of active
      ageing in older people, including those with mental disorders. BACKGROUND:
      Approximately 15% of older people aged 60 and above are experiencing a mental
      disorder. However, they are commonly unrecognized from health care providers.
      DESIGN: This study is an integrative review. Articles published between January
      2002 and March 2017 in English and in Thai were identified through searches of
      the databases CINAHL, MEDLINE, EMBASE, PsycINFO, and Thai LIS, as well as through
      manual searching. Methodologically high-quality research articles were included
      if they addressed the promotion of active ageing and related concepts, the impact
      of mental disorders on active ageing and related concepts, the perspective of
      older people regarding active ageing, and issues related to working with older
      people with mental health problems living in the community. RESULTS: A total of
      18 articles were included. The findings show that there is little evidence
      regarding the promotion of active ageing in older people with mental disorders.
      Older people with mental disorders were less likely to achieve successful ageing
      compared with those without mental disorders, suggesting they need support from
      health care providers. However, there are several barriers to care and working
      with older people with mental disorders at the community level. CONCLUSION: Of
      concern is that health professionals focus on the physical health of older people
      while mental health issues are overlooked.

PMID- 29601660
TI  - Atom-Economic Silver-Catalyzed Difunctionalization of the Isocyano Group with
      Cyclic Oximes: Towards Pyrimidinediones.
AB  - An unprecedented silver-catalyzed difunctionalization of the isocyano group with
      cyclic oximes is described. This method allows efficient and atom-economic
      assembly of a vast array of structurally novel and interesting pyrimidinediones,
      and tolerates a range of functionalities. The resulting products can be easily
      converted into some useful compounds. Furthermore, the method can also be applied
      for the late-stage modification of a few biologically active molecules.

PMID- 29601661
TI  - Recent advances in gene-enhanced bone tissue engineering.
AB  - The loss of bone tissue represents a critical clinical condition that is
      frequently faced by surgeons. Substantial progress has been made in the area of
      bone research, providing insight into the biology of bone under physiological and
      pathological conditions, as well as tools for the stimulation of bone
      regeneration. The present review discusses recent advances in the field of gene
      enhanced bone tissue engineering. Gene transfer strategies have emerged as highly
      effective tissue engineering approaches for supporting the repair of the
      musculoskeletal system. By contrast to treatment with recombinant proteins,
      genetically engineered cells can release growth factors at the site of injury
      over extended periods of time. Of particular interest are the expedited
      technologies that can be applied during a single surgical procedure in a cost
      effective manner, allowing translation from bench to bedside. Several promising
      methods based on the intra-operative genetic manipulation of autologous cells or
      tissue fragments have been developed in preclinical studies. Moreover, gene
      therapy for bone regeneration has entered the clinical stage with clinical trials
      for the repair of alveolar bone. Current trends in gene-enhanced bone engineering
      are also discussed with respect to the movement of the field towards expedited,
      translational approaches. It is possible that gene-enhanced bone tissue
      engineering will become a clinical reality within the next few years.

PMID- 29601662
TI  - African-American men and prostate cancer-specific mortality: a competing risk
      analysis of a large institutional cohort, 1989-2015.
AB  - Significant racial disparities in prostate cancer (PCa) outcomes have been
      reported, with African-American men (AAM) more likely to endure adverse oncologic
      outcomes. Despite efforts to dissipate racial disparities in PCa, a survival gap
      persists and it remains unclear to what extent this disparity can be explained by
      known clinicodemographic factors. In this study, we leveraged our large
      institutional database, spanning over 25 years, to investigate whether AAM
      continued to experience poor PCa outcomes and factors that may contribute to
      racial disparities in PCa. A total of 7307 patients diagnosed with PCa from 1989
      through 2015 were included. Associations of race and clinicodemographic
      characteristics were analyzed using chi-square for categorical and Mann-Whitney U
      test for continuous variables. Racial differences in prostate cancer outcomes
      were analyzed using competing risk analysis methods of Fine and Gray. Median
      follow-up time was 106 months. There were 2304 deaths recorded, of which 432
      resulted from PCa. AAM were more likely to be diagnosed at an earlier age (median
      60 vs. 65 years, P = <0.001) and were more likely to have >=1 comorbidities
      (13.6% vs. 7.5%, P < 0.001). In a multivariate competing risk model, adjusted for
      baseline covariates, AAM experienced significantly higher risk of PCSM compared
      to NHW men (HR, 1.62, 95% CI, 1.02-2.57, P = 0.03) NHW. Among men diagnosed at an
      older age (>60 years), racial differences in PCSM were more pronounced, with AAM
      experiencing higher rates of PCSM (HR, 2.05, 95% CI, 1.26-3.34, P = 0.003). After
      adjustment of clinicodemographic and potential risk factors, AAM continue to
      experience an increased risk of mortality from PCa, especially older AAM.
      Furthermore, AAM are more likely to be diagnosed at an early age and more likely
      to have higher comorbidity indices.

PMID- 29601663
TI  - Survival benefit of lymph node dissection in surgery for colon cancer in elderly
      patients: A multicenter propensity score-matched study in Japan.
AB  - INTRODUCTION: In surgery for elderly patients with colorectal cancer, it is
      unclear whether radical lymph node (LN) dissection safely offers a survival
      benefit. The aim of the study was to evaluate the impact of the LN yield in
      elderly patients undergoing surgery for colorectal cancer. METHODS: The subjects
      were selected from a surgical database of 2065 patients aged >=80 years old who
      underwent surgery for colorectal cancer at 41 hospitals in Japan between 2003 and
      2007. The patients were divided into groups according to the number LN harvested:
      <12 and >=12. Propensity scores were subsequently matched to balance the baseline
      characteristics. RESULTS: Of the 954 patients initially selected, 331 were in the
      <12 LN and 623 were in the >=12 LN group. After cases were matched, 293 patients
      were allocated to each group, and all covariates were balanced. For short-term
      outcomes, the time for surgery was longer in the >=12 LN group, but there was no
      significant difference in morbidity between the groups. Overall, relapse-free and
      cancer-specific survival rates were higher in the >=12 LN group (P = 0.004,
      0.001, and 0.02). CONCLUSIONS: In patients aged >=80 years old with stage II-III
      colon cancer, harvesting >=12 LN provides a survival benefit, and therefore,
      limited LN dissection is not recommended in these patients.

PMID- 29601664
TI  - Plant controls on Late Quaternary whole ecosystem structure and function.
AB  - Plants and animals influence biomass production and nutrient cycling in
      terrestrial ecosystems; however, their relative importance remains unclear. We
      assessed the extent to which mega-herbivore species controlled plant community
      composition and nutrient cycling, relative to other factors during and after the
      Late Quaternary extinction event in Britain and Ireland, when two-thirds of the
      region's mega-herbivore species went extinct. Warmer temperatures, plant-soil and
      plant-plant interactions, and reduced burning contributed to the expansion of
      woody plants and declining nitrogen availability in our five study ecosystems.
      Shrub biomass was consistently one of the strongest predictors of ecosystem
      change, equalling or exceeding the effects of other biotic and abiotic factors.
      In contrast, there was relatively little evidence for mega-herbivore control on
      plant community composition and nitrogen availability. The ability of plants to
      determine the fate of terrestrial ecosystems during periods of global
      environmental change may therefore be greater than previously thought.

PMID- 29601665
TI  - Indicators of transitions in biological systems.
AB  - In the face of global biodiversity declines, predicting the fate of biological
      systems is a key goal in ecology. One popular approach is the search for early
      warning signals (EWSs) based on alternative stable states theory. In this review,
      we cover the theory behind nonlinearity in dynamic systems and techniques to
      detect the loss of resilience that can indicate state transitions. We describe
      the research done on generic abundance-based signals of instability that are
      derived from the phenomenon of critical slowing down, which represent the genesis
      of EWSs research. We highlight some of the issues facing the detection of such
      signals in biological systems - which are inherently complex and show low signal
      to-noise ratios. We then document research on alternative signals of instability,
      including measuring shifts in spatial autocorrelation and trait dynamics, and
      discuss potential future directions for EWSs research based on detailed
      demographic and phenotypic data. We set EWSs research in the greater field of
      predictive ecology and weigh up the costs and benefits of simplicity vs.
      complexity in predictive models, and how the available data should steer the
      development of future methods. Finally, we identify some key unanswered questions
      that, if solved, could improve the applicability of these methods.

PMID- 29601667
TI  - Laparoscopic sigmoidectomy in a case of sigmoid colon cancer with situs inversus
      totalis.
AB  - Situs inversus totalis (SIT) is a rare anatomic anomaly in which organs in the
      chest and abdomen exist in a mirror image reversal of their normal positions. SIT
      can complicate surgical procedures, and few reports have described laparoscopic
      surgery for colorectal cancer in patients with SIT. Here, we report a case of
      successful laparoscopic surgery in a patient with SIT and sigmoid colon cancer.
      Laparoscopic sigmoidectomy involved colonic mobilization with high ligation of
      the inferior mesenteric vessels and complete mesocolic excision. The operating
      surgeon stood on the patient's left side, opposite the normal location for
      sigmoidectomy. By placing a 12-mm trocar in the left iliac fossa and using an
      automatic endoscopic linear stapler, the operating surgeon was able to perform
      left-handed colon resection without having to change position or move the
      laparoscopic monitor mid-procedure. An automatic endoscopic linear stapler is
      useful for laparoscopic left-side colon surgery in a patient with SIT.

PMID- 29601666
TI  - Trps1 is associated with the multidrug resistance of lung cancer cell by
      regulating MGMT gene expression.
AB  - Multidrug resistance (MDR) often leads to chemotherapy failure of lung cancer and
      has been linking to the cellular expression of several DNA transcription- and
      repair-related genes such as Trps1 and MGMT. However, their roles in the
      formation of MDR are largely unknown. In this study, overexpression/knockdown,
      luciferase assay and ChIP assay were performed to study the relationship between
      Trps1 and MGMT, as well as their roles in MDR formation. Our results demonstrated
      that Trps1 and MGMT expression both increased in drug-resistant lung cancer cell
      line (H446/CDDP). Silencing of Trps1 resulted in downregulation of MGMT
      expression and decrease in the multidrug sensitivity of H446/CDDP cells, while
      Trps1 overexpression exhibited the opposite effects in H446 cells. Ectopic
      expression of MGMT had no effect on Trps1 expression, but enhanced the IC50
      values of H446 cells or rescued the IC50 values of Trps1-silenced H446/CDDP cells
      in treatment of multidrug. Our data further showed that, mechanistically, Trps1
      acted as a transcription activator that directly induced MGMT transcription by
      binding to the MGMT promoter. Taken together, we consider that upregulation of
      Trps1 induces MGMT transcription contributing to the formation of MDR in lung
      cancer cells. Our findings proved potential targets for reversing MDR in clinical
      chemotherapy of lung cancer.

PMID- 29601668
TI  - Calcium plus magnesium indicates digestibility: the significance of the second
      major axis of plant chemical variation for ecological processes.
AB  - Plant variation in nutrient concentrations encompasses two major axes. The first
      is connected to nitrogen (N) and phosphorus (P), reflects growth rate and has
      been designated as the leaf economics spectrum (LES) while the second follows the
      gradient in calcium (Ca) and magnesium (Mg) and mirrors cell structural
      differences. Here, we tested in grasslands whether the sum Ca + Mg concentrations
      is a better indicator of digestibility than LES constituents. Structural equation
      modelling revealed that the total effect size of N (0.30) on digestibility was
      much lower than that of Ca + Mg (0.58). The N effect originated predominantly
      from sampling date (biomass ageing), while the Ca + Mg effect largely from
      phylogenetic composition (proportion of monocots). Thus, plant variation in
      partially substitutable divalent cations seems to play a significant role in
      biomass digestion by ruminants. This finding contests, together with litter
      decomposition studies, the prominent role of the LES for understanding both
      fundamental ecological processes.

PMID- 29601669
TI  - Canalisation in the wild: effects of developmental conditions on physiological
      traits are inversely linked to their association with fitness.
AB  - Ecological conditions affect fitness, but mechanisms causing such effects are not
      well known, while evolved responses to environmental variation may depend on the
      underlying mechanisms. Consequences of environmental conditions vary strongly
      between traits, but a framework to interpret such variation is lacking. We
      propose that variation in trait response may be explained by differential
      canalisation, with traits with larger fitness effects showing weaker responses to
      environmental perturbations due to preferential resource allocation to such
      traits. We tested the canalisation hypothesis using brood size manipulation in
      wild jackdaw nestlings in which we measured eight physiological traits (mainly
      oxidative stress markers), and two feather traits. For each trait, we estimated
      manipulation response and association with fitness (over-winter survival). As
      predicted, a strong negative correlation emerged between manipulation response
      and association with fitness (r =-0.76). We discuss the consequences of
      differential trait canalisation for the study of mechanisms mediating
      environmental effects on fitness.

PMID- 29601670
TI  - Species-area relationships and biodiversity loss in fragmented landscapes.
AB  - To estimate species loss from habitat destruction, ecologists typically use
      species-area relationships, but this approach neglects the spatial pattern of
      habitat fragmentation. Here, we provide new, easily applied, analytical methods
      that place upper and lower bounds on immediate species loss at any spatial scale
      and for any spatial pattern of habitat loss. Our formulas are expressed in terms
      of what we name the 'Preston function', which describes triphasic species-area
      relationships for contiguous regions. We apply our method to case studies of
      deforestation and tropical tree species loss at three different scales: a 50 ha
      forest plot in Panama, the tropical city-state of Singapore and the Brazilian
      Amazon. Our results show that immediate species loss is somewhat insensitive to
      fragmentation pattern at small scales but highly sensitive at larger scales:
      predicted species loss in the Amazon varies by a factor of 16 across different
      spatial structures of habitat loss.

PMID- 29601672
TI  - MRI-guided interventional natural killer cell delivery for liver tumor treatment.
AB  - While natural killer (NK) cell-based adoptive transfer immunotherapy (ATI)
      provides only modest clinical success in cancer patients. This study was
      hypothesized that MRI-guided transcatheter intra-hepatic arterial (IHA) infusion
      permits local delivery to liver tumors to improve outcomes during NK-based ATI in
      a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with
      clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to
      three groups: transcatheter IHA saline infusion as the control group,
      transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI
      studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion.
      There was a significant difference in tumor R2* values between baseline and 24 h
      following the selective transcatheter IHA NK delivery to the tumors (P = 0.039)
      when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were
      significant differences in tumor volumes between the control, IV, and IHA NK
      infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV
      vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2*
      value change (?R2*) at 24 h postinfusion and tumor volume change (?volume) at 8
      days in IHA group (R2  = 0.704, P < 0.001). Clinically applicable labeled NK
      cells with 12-h labeling time can be tracked by MRI. Transcatheter IHA infusion
      improves NK cell homing efficacy and immunotherapeutic efficiency. The change in
      tumor R2* value 24 h postinfusion is an important early biomarker for prediction
      of longitudinal response.

PMID- 29601671
TI  - The importance of greater speed in drug development for advanced malignancies.
AB  - It takes on average 6-12 years to develop new anticancer drugs from discovery to
      approval. Effective new agents prolong survival. To demonstrate the importance of
      rapid drug approval, we calculated life-years potentially saved if selected
      agents were approved more rapidly. As illustrative examples, we used 27 trials
      documenting improvements in survival. We multiplied improvement in median
      survival by numbers of patients dying annually and multiplied this by number of
      years from drug discovery until approval. For every year by which time to drug
      approval could have been shortened, there would have been a median number of life
      years potentially saved of 79,920 worldwide per drug. Median number of life-years
      lost between time of drug discovery and approval was 1,020,900 per example. If we
      were able to use available opportunities to decrease the time required to take a
      drug from discovery to approval to 5 years, the median number of life-years saved
      per example would have been 523,890 worldwide. Various publications have
      identified opportunities to speed drug development without sacrificing patient
      safety. While many investigational drugs prove to be ineffective, some
      significantly prolong survival and/or reduce suffering. These illustrative
      examples suggest that a substantial number of life-years could potentially be
      saved by increasing the efficiency of development of new drugs for advanced
      malignancies.

PMID- 29601673
TI  - Tumor-derived extracellular vesicles activate primary monocytes.
AB  - Tumor cells educate immune effector cells in their vicinity by releasing factors
      that manipulate their phenotype and function. In fact, the thus generated
      immunosuppressive tumor microenvironment constitutes an integral part and a
      hallmark of solid tumors and contributes significantly to tumor development and
      immune escape. It has long been thought that soluble factors like prostaglandin
      E2 and TGF-beta are the main mediators of these effects. But tumor cells also
      constantly release large number of extracellular vesicles (EVs), which are
      important conveyors of immune responses. We show here that tumor-derived EVs
      interact with primary monocytes and induce an activated phenotype, which is also
      observed in tumor-associated macrophages. Thus, both tumor-derived EVs and
      soluble factors together collaborate to form the immunosuppressive milieu of the
      tumor environment.

PMID- 29601674
TI  - RFX1 participates in doxorubicin-induced hepatitis B virus reactivation.
AB  - Cytotoxic chemotherapy drugs, including doxorubicin, can directly promote
      hepatitis B virus (HBV) replication, but the mechanism has not been fully
      clarified. This study investigated the potential mechanism underlying the
      cytotoxic chemotherapy-mediated direct promotion of HBV replication. We found
      that HBV replication and regulatory factor X box 1 gene (RFX1) expression were
      simultaneously promoted by doxorubicin treatment. The amount of RFX1 bound to the
      HBV enhancer I was significantly increased under doxorubicin treatment.
      Furthermore, the activity of doxorubicin in promoting HBV replication was
      significantly attenuated when the expression of endogenous RFX1 was knocked down,
      and the EP element of HBV enhancer I, an element that mediated the binding of
      RFX1 and HBV enhancer I, was mutated. In addition, two different sequences of the
      conserved EP element were found among HBV genotypes A-D, and doxorubicin could
      promote the replication of HBV harboring either of the conserved EP elements.
      Here, a novel pathway in which doxorubicin promoted HBV replication via RFX1 was
      identified, and it might participate in doxorubicin-induced HBV reactivation.
      These findings would be helpful in preventing HBV reactivation during anticancer
      chemotherapy.

PMID- 29601676
TI  - Our voices united: ADEE and ADEA.

PMID- 29601675
TI  - Impact of scientific and technological advances.
AB  - Advancements in research and technology are transforming our world. The dental
      profession is changing too, in the light of scientific discoveries that are
      advancing biological technology-from new biomaterials to unravelling the genetic
      make-up of the human being. As health professionals, we embrace a model of
      continuous quality improvement and lifelong learning. Our pedagogical approach to
      incorporating the plethora of scientific-technological advancements calls for us
      to shift our paradigm from emphasis on skill acquisition to knowledge
      application. The 2017 ADEE/ADEA workshop provided a forum to explore and discuss
      strategies to ensure faculty, students and, ultimately, patients are best
      positioned to exploit the opportunities that arise from integrating new
      technological advances and research outcomes. Participants discussed methods of
      incorporating the impact of new technologies and research findings into the
      education of our dental students. This report serves as a signpost of the way
      forward and how to promote incorporation of research and technology advances and
      lifelong learning into the dental education curriculum.

PMID- 29601677
TI  - Guest editorial: Inspiration through collaboration.

PMID- 29601678
TI  - Interprofessional education in dental education: An international perspective.
AB  - Interprofessional collaborative care (IPC) is defined as working within and
      across healthcare disciplines and is considered essential to achieve a more
      inclusive, patient-centred care, provide a means to support patient safety and
      address global healthcare provider shortages. Interprofessional education (IPE)
      provides the knowledge and experience students need to achieve these goals.
      ADEE/ADEA held a joint international meeting 8-9 May 2017, with IPE being one of
      four topic areas discussed. The highly interactive workshop format, where
      "everyone was an expert," supported discussion, sharing and creative problem
      solving of over seventy-one participants from twenty-nine countries. IPE
      participants broke out into five groups over a two-day period discussing three
      main areas: challenges and barriers to implementing IPE within their institution
      or country; discussion of successful models of introducing and assessing IPE
      initiatives, and exploring best practices and next steps for implementation for
      each group member. A mind-mapping model was used to graphically display
      participants' thoughts and suggestions. Key themes, revealed through the visual
      mind maps and discussion, included the following: IPE should lead to and enhance
      patient-centred care; student involvement is key to IPE success; faculty
      development and incentives can facilitate adoption and implementation of IPE; the
      role of a "champion" and leadership structure and commitment is important to move
      IPE forward; and IPE must be tailored to the unique issues found in each country.
      Overall, there was a high level of interest to continue both collaboration and
      discussion to learn from others beyond the London meeting.

PMID- 29601679
TI  - Shaping the future of dental education: Caries as a case-study.
AB  - This study reports on the full-day workshop "The Shape of The Future of Dental
      Education for Dental Caries-and how we get there" held immediately prior to the
      May 2017 ADEE/ADEA/King's College London meeting "Shaping the Future of Dental
      Education." A standardised, evidence-led Core Curriculum in Cariology (CCC) was
      developed jointly and systematically by ORCA and ADEE, starting in 2010. At the
      same time, the ICDAS Foundation was developing a comprehensive caries management
      system, ICCMSTM. The workshop reported on what has been achieved on a global
      basis by many building on these initiatives. The CCC has been, or is currently
      being, localised in a number of places around the world and has, in some
      countries, been successfully implemented. There are also other areas which are
      struggling more with the logistics of introducing it. The workshop presented
      geographical perspectives and experiences on implementing the CCC from Colombia,
      the United States and Europe, as well as professional perspectives from
      hygienists, students and policymakers. The workshop then considered the future of
      the CCC and the roles of Interprofessional Education, Technology, Global
      Networking and Assessment in a Global Context in 4 breakout groups. Having had
      reports back and plenary discussion, it was concluded that the caries world has
      made good progress towards a "futuristic" curriculum with parallel development of
      a comprehensive, preventive and tooth-preserving caries management system
      ICCMSTM. The implementation challenge is now to share even more effectively in
      order to have these developments more widely accepted and adopted worldwide.

PMID- 29601680
TI  - Global networking: Meeting the challenges, facilitating collaboration.
AB  - The constant change of information and technology advancement as well as the
      impact of social media has radically changed the world and education and, in
      particular, the needs of students, organisations and disadvantaged communities
      who share the aim of training and providing quality healthcare services. Dental
      organisations and education centres around the world have recognised the
      importance of networking in delivering effective education to students,
      healthcare professionals and communities. Networking is one way to meet the
      challenges of delivering healthcare education and services. This can be achieved
      by sharing of resources, expertise, knowledge and experience to benefit all the
      stakeholders in healthcare delivery. The joint ADEE/ADEA Meeting in London on 8-9
      May 2017 has facilitated discussions amongst dental educators from all over the
      world during a workshop on "Global Networking: the how and why for dental
      educators." The aim of this workshop was to determine how can dental educators
      worldwide network to share ideas, experience, expertise and resources to improve
      both the curricula and the teaching and learning environment. A pre-conference
      survey was designed and implemented to identify the domains of interest and needs
      of participants. A structured questionnaire was administered, and this
      information was used to guide discussions on three main themes: curricula,
      faculty development and mobility of faculty and students. Four questions were
      then defined to help group leaders to frame discussions in the four working
      groups. The four groups engaged in parallel discussions, with the ideas recorded
      and collated by group leaders, which later served for the thematic analysis
      across the groups to draw the key points discussed. Overall, a great desire and
      potential to create a global networking to share and gain support and expertise
      at individual and organisational level was apparent and the working group has
      proposed an action plan, acknowledging that it requires great planning, effort
      and commitment.

PMID- 29601681
TI  - The shape of the future of dental education for dental caries- and how we get
      there: Introduction to the ACFF Caries Workshop.

PMID- 29601682
TI  - Assessment in a global context: An international perspective on dental education.
AB  - Assessments are widely used in dental education to record the academic progress
      of students and ultimately determine whether they are ready to begin independent
      dental practice. Whilst some would consider this a "rite-of-passage" of learning,
      the concept of assessments in education is being challenged to allow the
      evolution of "assessment for learning." This serves as an economical use of
      learning resources whilst allowing our learners to prove their knowledge and
      skills and demonstrating competence. The Association for Dental Education in
      Europe and the American Dental Education Association held a joint international
      meeting in London in May 2017 allowing experts in dental education to come
      together for the purposes of Shaping the Future of Dental Education. Assessment
      in a Global Context was one topic in which international leaders could discuss
      different methods of assessment, identifying the positives, the pitfalls and
      critiquing the method of implementation to determine the optimum assessment for a
      learner studying to be a healthcare professional. A post-workshop survey
      identified that educators were thinking differently about assessment, instead of
      working as individuals providing isolated assessments; the general consensus was
      that a longitudinally orientated systematic and programmatic approach to
      assessment provide greater reliability and improved the ability to demonstrate
      learning.

PMID- 29601683
TI  - A golden age for Haemophilia treatment?

PMID- 29601685
TI  - Reflections On A Quality Journey.
AB  - Going for the gold unites staff and empowers them to make a difference.

PMID- 29601684
TI  - Ransomware Cyber Security Threat Tests Providers' Defenses.
AB  - A new breed of hackers is freezing health care and operational data and holding
      them hostage.

PMID- 29601686
TI  - Pharmaceutical Waste: A Checklist For Compliance.
AB  - The improper disposal of drugs isn't only an environmental threat, it can  put
      the center at risk of substantial penalties.

PMID- 29601688
TI  - ACOs Bring Assisted Living Into The Fold.

PMID- 29601687
TI  - Kindness Tops Residents' Wish Lists.
AB  - There are steps staff members can take to not only be perceived as friendlier,
      but to actually feel friendlier.

PMID- 29601689
TI  - Educating Patients On Sudden Death Syndrome In Epilepsy.
AB  - Recent studies highlight tips for long term and post-acute care providers to help
      patients and residents with epilepsy achieve freedom from seizures.

PMID- 29601690
TI  - ZPICs Use An Arsenal Of Weapons To Fight Fraud.
AB  - CMS recently made changes to Chapter 4 of the Medicare Program Integrity Manual,
      which include governance for ZPICs.

PMID- 29601691
TI  - For Rural Providers, Location Does Matter.
AB  - Delivering long term and post-acute care in a rural setting poses unique
      challenges and opportunities for skilled nursing providers.

PMID- 29601692
TI  - Antibiotic Stewardship Takes A Village.
AB  - Federal requirements in November 2017 call on long term care centers to have a
      program in place. Will providers be ready?

PMID- 29601693
TI  - How Kindred Won Nation's Highest Award For Performance Excellence.
AB  - A skilled nursing center from rural Idaho makes its mark in history.

PMID- 29601694
TI  - Determining Staff Competencies.
AB  - CMS' requirements of participation for skilled nursing facilities highlight the
      level of each staff member's skill set.

PMID- 29601695
TI  - Leading Through Team Building.
AB  - Nursing center academy prepares leaders for new regulatory requirements and
      performance-based health care.

PMID- 29601696
TI  - New Program Brings That Warm And Fuzzy Feeling.
AB  - Fostering two baby kittens draws out residents to reminisce about their pasts,
      engaging with others.

PMID- 29601697
TI  - Providers Offer Ailing Prisoners A Helping Hand.
AB  - The aging of the country's prison population is bringing higher rates of
      disabling conditions, with many needing long term/post-acute care services.

PMID- 29601698
TI  - Flu Vaccines Vital In Nursing, Assisted Living Settings.
AB  - People who are 65 and older are six times more likely to die from influenza and
      its complications than all other age groups combined.

PMID- 29601699
TI  - Our Humanity: Part 1
AB  - The Ultimate Goal and Measure in Long Term Care.

PMID- 29601700
TI  - Serving Up New Rules For Food And Dining.
AB  - CMS adds requirements for the oversight of providing the best sustenance possible
      for nursing care center residents.

PMID- 29601701
TI  - Making A Difference, One Life At A Time.
AB  - The Genesis Employee Foundation is a shining example of employees helping
      employees in times of need.

PMID- 29601702
TI  - Technology Comes Of Age In The LTC World.
AB  - The goal of sensor technology is to identify possible future chronic illnesses.

PMID- 29601703
TI  - Setting The Stage For 2017.
AB  - Seniors Housing, Skilled Nursing, And The Economy.

PMID- 29601704
TI  - OIG Puts Bull's-Eye On Rehospitalization.
AB  - Results of a study about adverse events in skilled nursing centers has led Agency
      to focus on prevention.

PMID- 29601705
TI  - Fault Lines And Frontiers In Person-Centered, Long Term Care: Part 2.

PMID- 29601706
TI  - Maintaining A Safe Workplace Takes Teamwork.
AB  - Educating employees, making sure they demonstrate proper lift techniques, and
      providing adequate equipment are key in fostering safety.

PMID- 29601707
TI  - Research Project Takes Personal Turn For Phoenix Symphony.

PMID- 29601708
TI  - Marijuana Laws Create Haze Around Policies.
AB  - The growing state legalization of the drug in the face of a federal ban poses a
      dilemma for providers.

PMID- 29601709
TI  - Skilled Nursing Center Data In For 2016.
AB  - Taking stock of the market's current and recent trends can help owners assess
      their business strategies.

PMID- 29601710
TI  - Fault Lines And Frontiers In Person-Centered, Long Term Care Part 3.

PMID- 29601711
TI  - Caregiver Shortage Reaches Critical Stage.
AB  - Stronger economy and shifting demographics put providers in bind in search for
      workers.

PMID- 29601712
TI  - Doomsday in the Workplace?
AB  - If the right leader is not hired, the company is doomed to crumble from the top
      down, taking good employees with it.

PMID- 29601713
TI  - Minimizing Litigation Risks In Skilled Nursing Care.
AB  - Accountable clinical processes aligned with EHR workflow can boost  risk
      management efforts.

PMID- 29601714
TI  - Shoring Up Section GG Can Protect Outcomes, Payment.
AB  - Accurate assessment of residents' functional abilities will help providers avoid
      pitfalls and establish outcomes.

PMID- 29601715
TI  - Finding a Path Through the Acronym Maze.
AB  - Providers must deal with new payment models governed by multiple statutes.

PMID- 29601716
TI  - Eight Characteristics of an Efficient Finance Department.
AB  - Assessing the finance department's strengths and weaknesses can help achieve
      solvency.

PMID- 29601717
TI  - The Link Between Falls And Brain Activity.
AB  - New research on falls and multi-tasking can bolster providers'  fall reduction
      strategies.

PMID- 29601718
TI  - Myth-Busting Medicare for Long Term Care Skilled Services
AB  - Debunking common medicare myths can help providers guide patients through
      complicated post-acute care coverage.

PMID- 29601719
TI  - Multi-metal, Multi-wavelength Surface-Enhanced Raman Spectroscopy Detection of
      Neurotransmitters.
AB  - The development of a sensor for the rapid and sensitive detection of
      neurotransmitters could provide a pathway for the diagnosis of neurological
      diseases, leading to the discovery of more effective treatment methods. We
      investigate the use of surface enhanced Raman spectroscopy (SERS) based sensors
      for the rapid detection of melatonin, serotonin, glutamate, dopamine, GABA,
      norepinephrine, and epinephrine. Previous studies have demonstrated SERS
      detection of neurotransmitters; however, there has been no comprehensive study on
      the effect of the metal used as the SERS substrate or the excitation wavelength
      used for detection. Here, we present the detection of 7 neurotransmitters using
      both silver and gold nanoparticles at excitation wavelengths of 532, 633, and 785
      nm. Over the range of wavelengths investigated, the SERS enhancement on the
      silver and gold nanoparticles varies, with an average enhancement factor of 105
      106. The maximum SERS enhancement occurs at an excitation wavelength of 785 nm
      for the gold nanoparticles and at 633 nm for the silver nanoparticles.

PMID- 29601720
TI  - Radiotherapy-Sensitized Tumor Photothermal Ablation Using gamma-Polyglutamic Acid
      Nanogels Loaded with Polypyrrole.
AB  - Development of versatile nanoscale platforms for cancer diagnosis and therapy is
      of great importance for applications in translational medicine. In this work, we
      present the use of gamma-polyglutamic acid (gamma-PGA) nanogels (NGs) to load
      polypyrrole (PPy) for thermal/photoacoustic (PA) imaging and radiotherapy (RT)
      sensitized tumor photothermal therapy (PTT). First, a double emulsion approach
      was used to prepare the cystamine dihydrochloride (Cys)-cross-linked gamma-PGA
      NGs. Next, the cross-linked NGs served as a reactor to be filled with pyrrole
      monomers that were subjected to in situ oxidation polymerization in the existence
      of Fe(III) ions. The formed uniform PPy-loaded NGs having an average diameter of
      38.9 +/- 8.6 nm exhibited good water-dispersibility and colloid stability. The
      prominent near-infrared (NIR) absorbance feature due to the loaded PPy endowed
      the NGs with contrast enhancement in PA imaging. The hybrid NGs possessed
      excellent photothermal conversion efficiency (64.7%) and stability against laser
      irradiation, and could be adopted for PA imaging and PTT of cancerous cells and
      tumor xenografts. Importantly, we also explored the cooperative PTT and X-ray
      radiation-mediated RT for enhanced tumor therapy. We show that PTT of tumors can
      be more significantly sensitized by RT using the sequence of laser irradiation
      followed by X-ray radiation as compared to using the reverse sequence. Our study
      suggests a promising theranostic platform of hybrid NGs that may be potentially
      utilized for PA imaging and combination therapy of different types of tumors.

PMID- 29601721
TI  - Dynamic Bonds between Boronic Acid and Alginate: Hydrogels with Stretchable, Self
      Healing, Stimuli-Responsive, Remoldable, and Adhesive Properties.
AB  - For the increasing demand of soft materials with wide ranges of applications,
      hydrogels have been developed exhibiting variety of functions (e.g., stretchable,
      self-healing, stimuli-responsive, and etc.). So far, add-in components such as
      inorganic nanoparticles, carbon materials, clays, and many others to main
      polymers have been used to achieve various unique functions of hydrogels. The
      multicomponent hydrogel systems often exhibit batch-dependent inconsistent
      results and problems in multicomponent mixings, require labors during
      preparations, and accompany unpredictable cross-talk between the added
      components. Here, we developed 'single polymeric component', alginate-boronic
      acid (alginate-BA) hydrogel to overcome the aforementioned problems. It exhibits
      unprecedented multifunctionalities simultaneously, such as high stretchability,
      self-healing, shear-thinning, pH- and glucose-sensitivities, adhesive properties,
      and reshaping properties. Multifunctionalities of alginate-BA hydrogel is
      resulted from the reversible inter- and intramolecular interactions by dynamic
      equilibrium of boronic acid-diol complexation and dissociation, which was proved
      by single molecule level Atomic Force Microscopy (AFM) pulling experiments. We
      also found that the alginate-BA gel showed enhanced in vivo retentions along
      gastrointestinal (GI) tract. Our findings suggest that rational polymer designs
      can result in minimizing the number of a participating component for
      multifunctional hydrogels, instead of increasing complexity by adding various
      additional components.

PMID- 29601722
TI  - Impact of Alternative Jet Fuels on Engine Exhaust Composition During the 2015
      ECLIF Ground-Based Measurements Campaign.
AB  - The application of fuels from renewable sources ("alternative fuels") in aviation
      is important for the reduction of anthropogenic carbon dioxide emissions, but may
      also attribute to reduced release of particles from jet engines. The present
      experiment describes ground-based measurements in the framework of the ECLIF
      (Emission and Climate Impact of Alternative Fuels) campaign using an Airbus A320
      (V2527-A5 engines) burning six fuels of chemically different composition. Two
      reference Jet A-1 with slightly different chemical parameters were applied and
      further used in combination with a Fischer-Tropsch synthetic paraffinic kerosene
      (FT-SPK) to prepare three semi synthetic jet fuels (SSJF) of different aromatic
      content. In addition, one commercially available fully synthetic jet fuel (FSJF)
      featured the lowest aromatic content of the fuel selection. Neither the release
      of nitrogen oxide or carbon monoxide was significantly affected by the different
      fuel composition. The measured particle emission indices showed a reduction up to
      50% (number) and 70% (mass) for two alternative jet fuels (FSJF, SSJF2) at low
      power settings in comparison to the reference fuels. The reduction is less
      pronounced at higher operating conditions but the release of particle number and
      particle mass is still significantly lower for the alternative fuels than for
      both reference fuels. The observed correlation between emitted particle mass and
      fuel aromatics is not strict. Here, the H/C ratio is a better indicator for soot
      emission.

PMID- 29601723
TI  - Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility
      Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2
      hydroxyethyl methacrylate) Hydrogels.
AB  - Under nonsink dissolution conditions, the kinetic-solubility profiles of
      amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so
      called "spring-and-parachute" concentration-time behaviors. However, the kinetic
      solubility profiles of ASDs based on insoluble carriers (including hydrogels) are
      known to show sustained supersaturation during nonsink dissolution through a
      matrix-regulated diffusion mechanism by which the supersaturation of the drug is
      built up gradually and sustained over an extended period without any dissolved
      polymers acting as crystallization inhibitors. Despite previous findings
      demonstrating the interplay between supersaturation rates and total doses on the
      kinetic-solubility profiles of soluble amorphous systems (including ASDs based on
      dissolution-regulated releases from soluble polymer carriers), the combined
      effects of supersaturation rates and doses on the kinetic-solubility profiles of
      ASDs based on diffusion-regulated releases from water-insoluble carriers have not
      been investigated previously. Thus, the objective of this study is to examine the
      impacts of total doses and supersaturation-generation rates on the resulting
      kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We
      employed a previously established ASD-carrier system based on water-insoluble
      cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two
      poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the
      weakly basic posaconazole (PCZ). Our results show clearly for the first time that
      by using the smallest-particle-size fraction and a high dose (i.e., above the
      critical dose), it is indeed possible to significantly shorten the duration of
      sustained supersaturation in the kinetic-solubility profile of an ASD based on a
      water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute
      dissolution profiles normally associated with ASDs based on soluble carriers.
      This generates sufficiently rapid initial supersaturation buildup above the
      critical supersaturation, resulting in more rapid precipitation. Above this
      smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of
      drug release gets slower, which results in a more modest rate of supersaturation
      buildup, leading to a maximum supersaturation below the critical-supersaturation
      level without appreciable precipitation. The area-under-the-curve (AUC) values of
      the in vitro kinetic-solubility concentration-time profiles were used to
      correlate the corresponding trends in dissolution enhancement. There are observed
      monotonic increases in AUC values with increasing particle sizes for high-dose
      ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously
      reported AUC maxima at some intermediate supersaturation rates or doses in
      soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the
      critical dose levels), crystallization would be negligible, leading to sustained
      supersaturation with all particle sizes (i.e., eventually reaching the same
      maximum supersaturation) and the smallest particle size reaching the maximum
      supersaturation the fastest. As a result, the smallest particle sizes yield the
      largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel
      matrixes. In addition to probing the interplay between the supersaturation
      generation rates and total doses in ASDs based on insoluble hydrogel carriers,
      our results further support the fact that through either increasing the hydrogel
      particle size or lowering the total dose to achieve maximum supersaturation still
      below the critical-supersaturation level, it is possible to avoid drug
      precipitation so as to maintain sustained supersaturation.

PMID- 29601724
TI  - Design and Application of Hybrid Phosphorus Ligands for Enantioselective Rh
      Catalyzed Anti-Markovnikov Hydroformylation of Unfunctionalized 1,1-Disubstituted
      Alkenes.
AB  - A series of novel hybrid phosphorus ligands were designed and applied to the Rh
      catalyzed enantioselective anti-Markovnikov hydroformylation of unfunctionalized
      1,1-disubstituted alkenes. By employing the new catalyst, linear aldehydes with
      beta-chirality can be prepared with high yields and enantioselectivities under
      mild conditions. Furthermore, catalyst loading as low as 0.05 mol % furnished the
      desired product in good yield and undiminished selectivity, demonstrating the
      efficiency of this transformation in large-scale synthesis.

PMID- 29601725
TI  - Enhanced Tribocorrosion Performance of Cr/GLC Multilayered Films for Marine
      Protective Application.
AB  - The corrosion and tribology are all closely related to the interface/surface of
      materials, which are extremely important for the mechanical components used in
      harsh marine environments. In this work, we fabricated Cr/graphite-like carbon
      (GLC) multilayered films with different modulation periods on the 316L stainless
      steels by direct current magnetron sputtering. Tribocorrosion tests in artificial
      seawater show that the tribocorrosion resistance of the Cr/GLC films is improved
      as the modulation period decreases from 1000 to 333 nm and then drastically drops
      with further decreasing to 250 nm. By taking a top-layer thickening strategy for
      the Cr/GLC film with 250 nm modulation period, the tribocorrosion performance is
      significantly enhanced. The corresponded mechanisms are discussed in terms of the
      film structure and electrochemical corrosion behavior.

PMID- 29601726
TI  - Atmospheric OH Oxidation of Three Chlorinated Aromatic Herbicides.
AB  - Chlorinated phenoxy acids are a widely used class of herbicides and have been
      found in remote regions far from sources. However, the atmospheric chemistry of
      these compounds is poorly understood. We use an oxidative flow reactor coupled to
      chemical ionization mass spectrometry to investigate OH oxidation of two
      chlorinated phenoxyacid herbicides (2-methyl-4-chlorophenoxyacetic acid (MCPA)
      and mecoprop-p) and one chlorinated pyridine herbicide (triclopyr). OH radicals
      add to the aromatic rings of the three herbicides, produce peroxides via hydrogen
      abstraction, or fragment at the ether bond. OH oxidation of MCPA produced two
      potentially toxic compounds: chlorosalicylaldehyde and chlorosalicylic acid. We
      use standards to validate the detection of these oxidation products by acetate
      CIMS and quantify the reaction rate. Oxidation of triclopyr produced a known
      endocrine disruptor, 3,5,6-trichloro-2-pyridinol. Thus, while some OH oxidation
      products are less toxic than the parent molecules (e.g., C1-5 carboxylic acids),
      others may be as or more toxic than the parent herbicide. We determine effective
      rate coefficients for OH addition to the aromatic ring ( kOH) for mecoprop-p of
      1.5 (+/-0.7) * 10-12 cm3 molecules-1 s-1 and for MCPA of 2.6 (+/-0.3) * 10-12 cm3
      molecules-1 s-1. The atmospheric lifetimes with respect to OH are thus long
      enough that photochemistry may be relevant to the environmental fate of these
      pesticides.

PMID- 29601727
TI  - Paradoxical Effect of Trehalose on the Aggregation of alpha-Synuclein: Expedites
      Onset of Aggregation yet Reduces Fibril Load.
AB  - Aggregation of alpha-synuclein is closely connected to the pathology of
      Parkinson's disease. The phenomenon involves multiple steps, commenced by partial
      misfolding and eventually leading to mature amyloid fibril formation. Trehalose,
      a widely accepted osmolyte, has been shown previously to inhibit aggregation of
      various globular proteins owing to its ability to prevent the initial unfolding
      of protein. In this study, we have examined if it behaves in a similar fashion
      with intrinsically disordered protein alpha-synuclein and possesses the potential
      to act as therapeutic agent against Parkinson's disease. It was observed
      experimentally that samples coincubated with trehalose fibrillate faster compared
      to the case in its absence. Molecular dynamics simulations suggested that this
      initial acceleration is manifestation of trehalose's tendency to perturb the
      conformational transitions between different conformers of monomeric protein. It
      stabilizes the aggregation prone "extended" conformer of alpha-synuclein, by
      binding to its exposed acidic residues of the C terminus. It also favors the beta
      rich oligomers once formed. Interestingly, the total fibrils formed are still
      promisingly less since it accelerates the competing pathway toward formation of
      amorphous aggregates.

PMID- 29601728
TI  - Engineered Coiled-Coil Protein for Delivery of Inverse Agonist for
      Osteoarthritis.
AB  - Osteoarthritis (OA) results from degenerative and abnormal function of joints,
      with localized biochemistry playing a critical role in its onset and progression.
      As high levels of all- trans retinoic acid (ATRA) in synovial fluid have been
      identified as a contributive factor to OA, the synthesis of de novo antagonists
      for retinoic acid receptors (RARs) has been exploited to interrupt the mechanism
      of ATRA action. BMS493, a pan-RAR inverse agonist, has been reported as an
      effective inhibitor of ATRA signaling pathway; however, it is unstable and
      rapidly degrades under physiological conditions. We employed an engineered
      cartilage oligomeric matrix protein coiled-coil (CccS) protein for the
      encapsulation, protection, and delivery of BMS493. In this study, we determine
      the binding affinity of CccS to BMS493 and the stimulator, ATRA, via competitive
      binding assay, in which ATRA exhibits approximately 5-fold superior association
      with CccS than BMS493. Interrogation of the structure of CccS indicates that ATRA
      causes about 10% loss in helicity, while BMS493 did not impact the structure.
      Furthermore, CccS self-assembles into nanofibers when bound to BMS493 or ATRA as
      expected, displaying 11-15 nm in diameter. Treatment of human articular
      chondrocytes in vitro reveals that CccS.BMS493 demonstrates a marked improvement
      in efficacy in reducing the mRNA levels of matrix metalloproteinase-13 (MMP-13),
      one of the main proteases responsible for the degradation of the extracellular
      cartilage matrix compared to BMS493 alone in the presence of ATRA, interleukin-1
      beta (IL-1beta), or IL-1 beta together with ATRA. These results support the
      feasibility of utilizing coiled-coil proteins as drug delivery vehicles for
      compounds of relatively limited bioavailability for the potential treatment of
      OA.

PMID- 29601729
TI  - Poly(ethylene oxide monomethyl ether)- block-poly(propylene succinate)
      Nanoparticles: Synthesis and Characterization, Enzymatic and Cellular
      Degradation, Micellar Solubilization of Paclitaxel, and in Vitro and in Vivo
      Evaluation.
AB  - Polyester-based nanostructures are widely studied as drug-delivery systems due to
      their biocompatibility and biodegradability. They are already used in the clinic.
      In this work, we describe a new and simple biodegradable and biocompatible system
      as the Food and Drug Administration approved polyesters (poly-epsilon
      caprolactone, polylactic acid, and poly(lactic- co-glycolic acid)) for the
      delivery of the anticancer drug paclitaxel (PTX) as a model drug. A hydrophobic
      polyester, poly(propylene succinate) (PPS), was prepared from a nontoxic alcohol
      (propylene glycol) and monomer from the Krebs's cycle (succinic acid) in two
      steps via esterification and melt polycondensation. Furthermore, their
      amphiphilic block copolyester, poly(ethylene oxide monomethyl ether)- block
      poly(propylene succinate) (mPEO- b-PPS), was prepared by three steps via
      esterification followed by melt polycondensation and the addition of mPEO to the
      PPS macromolecules. Analysis of the in vitro cellular behavior of the prepared
      nanoparticle carriers (NPs) (enzymatic degradation, uptake, localization, and
      fluorescence resonance energy-transfer pair degradation studies) was performed by
      fluorescence studies. PTX was loaded to the NPs of variable sizes (30, 70, and
      150 nm), and their in vitro release was evaluated in different cell models and
      compared with commercial PTX formulations. The mPEO- b-PPS copolymer analysis
      displays glass transition temperature < body temperature < melting temperature,
      lower toxicity (including the toxicity of their degradation products), drug
      solubilization efficacy, stability against spontaneous hydrolysis during
      transport in bloodstream, and simultaneous enzymatic degradability after uptake
      into the cells. The detailed cytotoxicity in vitro and in vivo tumor efficacy
      studies have shown the superior efficacy of the NPs compared with PTX and PTX
      commercial formulations.

PMID- 29601730
TI  - Hu Replies.

PMID- 29601731
TI  - Nanoscale Rheology and Anisotropic Diffusion Using Single Gold Nanorod Probes.
AB  - The complex rotational and translational Brownian motion of anisotropic particles
      depends on their shape and the viscoelasticity of their surroundings. Because of
      their strong optical scattering and chemical versatility, gold nanorods would
      seem to provide the ultimate probes of rheology at the nanoscale, but the
      suitably accurate orientational tracking required to compute rheology has not
      been demonstrated. Here we image single gold nanorods with a laser-illuminated
      dark-field microscope and use optical polarization to determine their three
      dimensional orientation to better than one degree. We convert the rotational
      diffusion of single nanorods in viscoelastic polyethylene glycol solutions to
      rheology and obtain excellent agreement with bulk measurements. Extensions of
      earlier models of anisotropic translational diffusion to three dimensions and
      viscoelastic fluids give excellent agreement with the observed motion of single
      nanorods. We find that nanorod tracking provides a uniquely capable approach to
      microrheology and provides a powerful tool for probing nanoscale dynamics and
      structure in a range of soft materials.

PMID- 29601732
TI  - Topological pi Junctions from Crossed Andreev Reflection in the Quantum Hall
      Regime.
AB  - We consider a two-dimensional electron gas (2DEG) in the quantum Hall regime in
      the presence of a Zeeman field, with the Fermi level tuned to a filling factor of
      nu=1. We show that, in the presence of spin-orbit coupling, contacting the 2DEG
      with a narrow strip of an s-wave superconductor produces a topological
      superconducting gap along the contact as a result of crossed Andreev reflection
      (CAR) processes across the strip. The sign of the topological gap, controlled by
      the CAR amplitude, depends periodically on the Fermi wavelength and strip width
      and can be externally tuned. An interface between two halves of a long strip with
      topological gaps of opposite sign implements a robust pi junction, hosting a pair
      of Majorana zero modes that do not split despite their overlap. We show that such
      a configuration can be exploited to perform protected non-Abelian tunnel-braid
      operations without any fine tuning.

PMID- 29601733
TI  - Valley Topological Phases in Bilayer Sonic Crystals.
AB  - Recently, the topological physics in artificial crystals for classical waves has
      become an emerging research area. In this Letter, we propose a unique bilayer
      design of sonic crystals that are constructed by two layers of coupled hexagonal
      array of triangular scatterers. Assisted by the additional layer degree of
      freedom, a rich topological phase diagram is achieved by simply rotating
      scatterers in both layers. Under a unified theoretical framework, two kinds of
      valley-projected topological acoustic insulators are distinguished analytically,
      i.e., the layer-mixed and layer-polarized topological valley Hall phases,
      respectively. The theory is evidently confirmed by our numerical and experimental
      observations of the nontrivial edge states that propagate along the interfaces
      separating different topological phases. Various applications such as sound
      communications in integrated devices can be anticipated by the intriguing
      acoustic edge states enriched by the layer information.

PMID- 29601734
TI  - Unusual Phonon Heat Transport in alpha-RuCl_{3}: Strong Spin-Phonon Scattering
      and Field-Induced Spin Gap.
AB  - The honeycomb Kitaev-Heisenberg model is a source of a quantum spin liquid with
      Majorana fermions and gauge flux excitations as fractional quasiparticles. Here
      we unveil the highly unusual low-temperature heat conductivity kappa of alpha
      RuCl_{3}, a prime candidate for realizing such physics: beyond a magnetic field
      of B_{c}~7.5  T, kappa increases by about one order of magnitude, both for in
      plane as well as out-of-plane transport. This clarifies the unusual magnetic
      field dependence unambiguously to be the result of severe scattering of phonons
      off putative Kitaev-Heisenberg excitations in combination with a drastic field
      induced change of the magnetic excitation spectrum. In particular, an unexpected,
      large energy gap arises, which increases linearly with the magnetic field,
      reaching remarkable homega_{0}/k_{B}~50  K at 18 T.

PMID- 29601735
TI  - Electrochemical Impedance Imaging via the Distribution of Diffusion Times.
AB  - We develop a mathematical framework to analyze electrochemical impedance spectra
      in terms of a distribution of diffusion times (DDT) for a parallel array of
      random finite-length Warburg (diffusion) or Gerischer (reaction-diffusion)
      circuit elements. A robust DDT inversion method is presented based on complex
      nonlinear least squares regression with Tikhonov regularization and illustrated
      for three cases of nanostructured electrodes for energy conversion: (i) a carbon
      nanotube supercapacitor, (ii) a silicon nanowire Li-ion battery, and (iii) a
      porous-carbon vanadium flow battery. The results demonstrate the feasibility of
      nondestructive "impedance imaging" to infer microstructural statistics of random,
      heterogeneous materials.

PMID- 29601736
TI  - Nonresonant Local Fields Enhance Second-Harmonic Generation from Metal
      Nanoislands with Dielectric Cover.
AB  - We study second-harmonic generation from gold nanoislands covered with amorphous
      titanium oxide (TiO_{2}) films. As the TiO_{2} thickness increases, the plasmon
      resonance of the nanoislands shifts away from the second-harmonic wavelength of
      532 nm, diminishing the resonant enhancement of the process at this wavelength.
      Nevertheless, the second-harmonic signal is enhanced by up to a factor of 45 with
      increasing TiO_{2} thickness. This unexpected effect arises from the scaling of
      local fields at the fundamental wavelength of 1064 nm-which is at the far tail of
      the resonance-due to a change in the dielectric environment of the nanoislands.

PMID- 29601737
TI  - Alignment and Imaging of the CS_{2} Dimer Inside Helium Nanodroplets.
AB  - The carbon disulphide (CS_{2}) dimer is formed inside He nanodroplets and
      identified using fs laser-induced Coulomb explosion, by observing the CS_{2}^{+}
      ion recoil velocity. It is then shown that a 160 ps moderately intense laser
      pulse can align the dimer in advantageous spatial orientations which allow us to
      determine the cross-shaped structure of the dimer by analysis of the correlations
      between the emission angles of the nascent CS_{2}^{+} and S^{+} ions, following
      the explosion process. Our method will enable fs time-resolved structural imaging
      of weakly bound molecular complexes during conformational isomerization,
      including formation of exciplexes.

PMID- 29601738
TI  - Renormalization in Large Momentum Effective Theory of Parton Physics.
AB  - In the large-momentum effective field theory approach to parton physics, the
      matrix elements of nonlocal operators of quark and gluon fields, linked by
      straight Wilson lines in a spatial direction, are calculated in lattice quantum
      chromodynamics as a function of hadron momentum. Using the heavy-quark effective
      theory formalism, we show a multiplicative renormalization of these operators at
      all orders in perturbation theory, both in dimensional and lattice
      regularizations. The result provides a theoretical basis for extracting parton
      properties through properly renormalized observables in Monte Carlo simulations.

PMID- 29601739
TI  - Near-Threshold Ionization of Argon by Positron Impact.
AB  - The direct single-ionization cross section for Ar by positron impact has been
      measured in the region above the first ionization threshold. These measurements
      are compared to semiclassical calculations which give rise to a power law
      variation of the cross section in the threshold region. The experimental results
      appear to be in disagreement with extensions to the Wannier theory applied to
      positron impact ionization, with a smaller exponent than that calculated by most
      previous works. In fact, in this work, we see no difference in threshold behavior
      between the positron and electron cases. Possible reasons for this discrepancy
      are discussed.

PMID- 29601740
TI  - Laser-Induced Skyrmion Writing and Erasing in an Ultrafast Cryo-Lorentz
      Transmission Electron Microscope.
AB  - We demonstrate that light-induced heat pulses of different duration and energy
      can write Skyrmions in a broad range of temperatures and magnetic field in FeGe.
      Using a combination of camera-rate and pump-probe cryo-Lorentz transmission
      electron microscopy, we directly resolve the spatiotemporal evolution of the
      magnetization ensuing optical excitation. The Skyrmion lattice was found to
      maintain its structural properties during the laser-induced demagnetization, and
      its recovery to the initial state happened in the sub-MUs to MUs range, depending
      on the cooling rate of the system.

PMID- 29601741
TI  - Origin of Negative Capacitance in Bipolar Organic Diodes.
AB  - Negative differential capacitance (NC) occurring at low frequencies in organic
      light-emitting diodes (OLEDs) is a poorly understood phenomenon. We study the
      origin of the NC effect by systematically varying the number of electron traps in
      OLEDs based on the polymeric semiconductor poly(p-phenylene vinylene). Increasing
      the electron trap density enhances the NC effect. The magnitude and observed
      decrease of the relaxation time is consistent with the (inverse) rate of trap
      assisted recombination. The absence of NC in a nearly trap-free light-emitting
      diode unambiguously shows that trap-assisted recombination is the responsible
      mechanism for the negative contribution to the capacitance in bipolar organic
      diodes. Our results reveal that the NC effect can be exploited to quantitatively
      determine the number of traps in organic semiconductors in a nondestructive
      fashion.

PMID- 29601742
TI  - Duality in Power-Law Localization in Disordered One-Dimensional Systems.
AB  - The transport of excitations between pinned particles in many physical systems
      may be mapped to single-particle models with power-law hopping, 1/r^{a}. For
      randomly spaced particles, these models present an effective peculiar disorder
      that leads to surprising localization properties. We show that in one-dimensional
      systems almost all eigenstates (except for a few states close to the ground
      state) are power-law localized for any value of a>0. Moreover, we show that our
      model is an example of a new universality class of models with power-law hopping,
      characterized by a duality between systems with long-range hops (a<1) and short
      range hops (a>1), in which the wave function amplitude falls off algebraically
      with the same power gamma from the localization center.

PMID- 29601743
TI  - Publisher's Note: Incoherence-Mediated Remote Synchronization [Phys. Rev. Lett.
      118, 174102 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.174102.

PMID- 29601744
TI  - Localization of Interacting Dirac Fermions.
AB  - Using exact quantum Monte Carlo calculations, we examine the interplay between
      localization of electronic states driven by many-body correlations and that by
      randomness in a two-dimensional system featuring linearly vanishing density of
      states at the Fermi level. A novel disorder-induced nonmagnetic insulating phase
      is found to emerge from the zero-temperature quantum critical point separating a
      semimetal and a Mott insulator. Within this phase, a phase transition from a
      gapless Anderson-like insulator to a gapped Mott-like insulator is identified.
      Implications of the phase diagram are also discussed.

PMID- 29601745
TI  - High-Power Collective Charging of a Solid-State Quantum Battery.
AB  - Quantum information theorems state that it is possible to exploit collective
      quantum resources to greatly enhance the charging power of quantum batteries
      (QBs) made of many identical elementary units. We here present and solve a model
      of a QB that can be engineered in solid-state architectures. It consists of N two
      level systems coupled to a single photonic mode in a cavity. We contrast this
      collective model ("Dicke QB"), whereby entanglement is genuinely created by the
      common photonic mode, to the one in which each two-level system is coupled to its
      own separate cavity mode ("Rabi QB"). By employing exact diagonalization, we
      demonstrate the emergence of a quantum advantage in the charging power of Dicke
      QBs, which scales like sqrt[N] for N?1.

PMID- 29601746
TI  - Continuous Easy-Plane Deconfined Phase Transition on the Kagome Lattice.
AB  - We use large scale quantum Monte Carlo simulations to study an extended Hubbard
      model of hard core bosons on the kagome lattice. In the limit of strong nearest
      neighbor interactions at 1/3 filling, the interplay between frustration and
      quantum fluctuations leads to a valence bond solid ground state. The system
      undergoes a quantum phase transition to a superfluid phase as the interaction
      strength is decreased. It is still under debate whether the transition is weakly
      first order or represents an unconventional continuous phase transition. We
      present a theory in terms of an easy plane noncompact CP^{1} gauge theory
      describing the phase transition at 1/3 filling. Utilizing large scale quantum
      Monte Carlo simulations with parallel tempering in the canonical ensemble up to
      15552 spins, we provide evidence that the phase transition is continuous at
      exactly 1/3 filling. A careful finite size scaling analysis reveals an
      unconventional scaling behavior hinting at deconfined quantum criticality.

PMID- 29601747
TI  - Ab Initio Calculation of the Miscibility Diagram for Hydrogen-Helium Mixtures.
AB  - We use finite-temperature density functional theory coupled to classical
      molecular dynamics simulation to calculate the miscibility gap of hydrogen-helium
      mixtures. The van der Waals density functional (vdW-DF) theory is used, which
      leads to lower demixing temperatures compared to computations using the Perdew
      Burke-Ernzerhof functional. Our calculations suggest that current Jupiter models
      are most likely too hot to allow demixing in the interior. A Jupiter isentrope
      based on our vdW-DF data is presented. Our demixing phase diagram still predicts
      phase separation in Saturn, but in a significantly reduced fraction of its
      volume.

PMID- 29601748
TI  - Three Phase-Grating Moire Neutron Interferometer for Large Interferometer Area
      Applications.
AB  - We demonstrate a three phase-grating moire neutron interferometer in a highly
      intense neutron beam as a robust candidate for large area interferometry
      applications and for the characterization of materials. This novel far-field
      moire technique allows for broad wavelength acceptance and relaxed requirements
      related to fabrication and alignment, thus circumventing the main obstacles
      associated with perfect crystal neutron interferometry. We observed interference
      fringes with an interferometer length of 4 m and examined the effects of an
      aluminum 6061 alloy sample on the coherence of the system. Experiments to measure
      the autocorrelation length of samples and the universal gravitational constant
      are proposed and discussed.

PMID- 29601749
TI  - Prediction of a Large-Gap and Switchable Kane-Mele Quantum Spin Hall Insulator.
AB  - Fundamental research and technological applications of topological insulators are
      hindered by the rarity of materials exhibiting a robust topologically nontrivial
      phase, especially in two dimensions. Here, by means of extensive first-principles
      calculations, we propose a novel quantum spin Hall insulator with a sizable band
      gap of ~0.5  eV that is a monolayer of jacutingaite, a naturally occurring
      layered mineral first discovered in 2008 in Brazil and recently synthesized. This
      system realizes the paradigmatic Kane-Mele model for quantum spin Hall insulators
      in a potentially exfoliable two-dimensional monolayer, with helical edge states
      that are robust and that can be manipulated exploiting a unique strong interplay
      between spin-orbit coupling, crystal-symmetry breaking, and dielectric response.

PMID- 29601750
TI  - Resolving Point Defects in the Hydration Structure of Calcite (10.4) with Three
      Dimensional Atomic Force Microscopy.
AB  - It seems natural to assume that defects at mineral surfaces critically influence
      interfacial processes such as the dissolution and growth of minerals in water.
      The experimental verification of this claim, however, is challenging and requires
      real-space methods with utmost spatial resolution, such as atomic force
      microscopy (AFM). While defects at mineral-water interfaces have been resolved in
      2D AFM images before, the perturbation of the surrounding hydration structure has
      not yet been analyzed experimentally. In this Letter, we demonstrate that point
      defects on the most stable and naturally abundant calcite (10.4) surface can be
      resolved using high-resolution 3D AFM-even within the fifth hydration layer. Our
      analysis of the hydration structure surrounding the point defect shows a
      perturbation of the hydration with a lateral extent of approximately one unit
      cell. These experimental results are corroborated by molecular dynamics
      simulations.

PMID- 29601752
TI  - Janus and Huygens Dipoles: Near-Field Directionality Beyond Spin-Momentum
      Locking.
AB  - Unidirectional scattering from circularly polarized dipoles has been demonstrated
      in near-field optics, where the quantum spin-Hall effect of light translates into
      spin-momentum locking. By considering the whole electromagnetic field, instead of
      its spin component alone, near-field directionality can be achieved beyond spin
      momentum locking. This unveils the existence of the Janus dipole, with side
      dependent topologically protected coupling to waveguides, and reveals the near
      field directionality of Huygens dipoles, generalizing Kerker's condition.
      Circular dipoles, together with Huygens and Janus sources, form the complete set
      of all possible directional dipolar sources in the far- and near-field. This
      allows the designing of directional emission, scattering, and waveguiding,
      fundamental for quantum optical technology, integrated nanophotonics, and new
      metasurface designs.

PMID- 29601753
TI  - Direct Measurement of Lateral Correlations under Controlled Nanoconfinement.
AB  - Lateral correlations along hydrophobic surfaces whose separation can be varied
      continuously are measured by x-ray scattering using a modified surface force
      apparatus coupled with synchrotron radiation, named SFAX. A weak isotropic
      diffuse scattering along the equatorial plane is revealed for mica surfaces
      rendered hydrophobic and charge neutral by immersion in cationic surfactant
      solutions at low concentrations. The peak corresponds to a lateral surface
      correlation length xi~12  nm, without long-range order. These findings are
      compatible with the atomic force microscopy imaging of a single surface, where
      adsorbed surfactant stripes appear surrounded by bare mica zones. Remarkably, the
      scattering patterns remain stable for gap widths D larger than the lateral period
      but change in intensity and shape (to a lesser extent) as soon as D<xi. This
      evolution codes for a redistribution of counterions (counterion release from
      antagonistic patches) and the associated new x-ray labeling of the patterns. The
      redistribution of counterions is also the key mechanism to the long-range
      electrostatic attraction between similar, overall charge-neutral walls, reported
      earlier.

PMID- 29601751
TI  - Observation of High Transformer Ratio of Shaped Bunch Generated by an Emittance
      Exchange Beam Line.
AB  - Collinear wakefield acceleration has been long established as a method capable of
      generating ultrahigh acceleration gradients. Because of the success on this
      front, recently, more efforts have shifted towards developing methods to raise
      the transformer ratio (TR). This figure of merit is defined as the ratio of the
      peak acceleration field behind the drive bunch to the peak deceleration field
      inside the drive bunch. TR is always less than 2 for temporally symmetric drive
      bunch distributions and therefore recent efforts have focused on generating
      asymmetric distributions to overcome this limitation. In this Letter, we report
      on using the emittance-exchange method to generate a shaped drive bunch to
      experimentally demonstrate a TR~5 in a dielectric wakefield accelerator.

PMID- 29601754
TI  - Clean Floquet Time Crystals: Models and Realizations in Cold Atoms.
AB  - Time crystals, a phase showing spontaneous breaking of time-translation symmetry,
      has been an intriguing subject for systems far away from equilibrium. Recent
      experiments found such a phase in both the presence and the absence of
      localization, while in theories localization by disorder is usually assumed a
      priori. In this work, we point out that time crystals can generally exist in
      systems without disorder. A series of clean quasi-one-dimensional models under
      Floquet driving are proposed to demonstrate this unexpected result in principle.
      Robust time crystalline orders are found in the strongly interacting regime along
      with the emergent integrals of motion in the dynamical system, which can be
      characterized by level statistics and the out-of-time-ordered correlators. We
      propose two cold atom experimental schemes to realize the clean Floquet time
      crystals, one by making use of dipolar gases and another by synthetic dimensions.

PMID- 29601755
TI  - Off-Shell Higgs Probe of Naturalness.
AB  - Examining the Higgs sector at high energy scales through off-shell Higgs
      production can potentially shed light on the naturalness problem of the Higgs
      boson mass. We propose such a study at the LHC by utilizing a representative
      model with a new scalar field (S) coupled to the standard model Higgs doublet (H)
      in a form |S|^{2}|H|^{2}. In the process pp->h^{*}->ZZ, the dominant momentum
      dependent part of the one-loop scalar singlet corrections, especially above the
      new threshold at 2m_{S}, leads to a measurable deviation in the differential
      distribution of the Z-pair invariant mass, in accordance with the quadratic
      divergence cancellation to the Higgs mass. We find that it is conceivable to
      probe such new physics at the 5sigma level at the high-luminosity LHC, improving
      further with the upgraded 27 TeV LHC, without requiring the precise measurement
      of the Higgs boson total width. The discovery of such a Higgs portal could also
      have important implications for thermal dark matter as well as for electroweak
      baryogenesis.

PMID- 29601756
TI  - Photon Subtraction by Many-Body Decoherence.
AB  - We experimentally and theoretically investigate the scattering of a photonic
      quantum field from another stored in a strongly interacting atomic Rydberg
      ensemble. Considering the many-body limit of this problem, we derive an exact
      solution to the scattering-induced spatial decoherence of multiple stored
      photons, allowing for a rigorous understanding of the underlying dissipative
      quantum dynamics. Combined with our experiments, this analysis reveals a
      correlated coherence-protection process in which the scattering from one
      excitation can shield all others from spatial decoherence. We discuss how this
      effect can be used to manipulate light at the quantum level, providing a robust
      mechanism for single-photon subtraction, and experimentally demonstrate this
      capability.

PMID- 29601757
TI  - Avalanches and Criticality in Driven Magnetic Skyrmions.
AB  - We show using numerical simulations that slowly driven Skyrmions interacting with
      random pinning move via correlated jumps or avalanches. The avalanches exhibit
      power-law distributions in their duration and size, and the average avalanche
      shape for different avalanche durations can be scaled to a universal function, in
      agreement with theoretical predictions for systems in a nonequilibrium critical
      state. A distinctive feature of Skyrmions is the influence of the nondissipative
      Magnus term. When we increase the ratio of the Magnus term to the damping term, a
      change in the universality class of the behavior occurs, the average avalanche
      shape becomes increasingly asymmetric, and individual avalanches exhibit motion
      in the direction perpendicular to their own density gradient.

PMID- 29601758
TI  - Quantum Simulation of Electronic Structure with Linear Depth and Connectivity.
AB  - As physical implementations of quantum architectures emerge, it is increasingly
      important to consider the cost of algorithms for practical connectivities between
      qubits. We show that by using an arrangement of gates that we term the fermionic
      swap network, we can simulate a Trotter step of the electronic structure
      Hamiltonian in exactly N depth and with N^{2}/2 two-qubit entangling gates, and
      prepare arbitrary Slater determinants in at most N/2 depth, all assuming only a
      minimal, linearly connected architecture. We conjecture that no explicit Trotter
      step of the electronic structure Hamiltonian is possible with fewer entangling
      gates, even with arbitrary connectivities. These results represent significant
      practical improvements on the cost of most Trotter-based algorithms for both
      variational and phase-estimation-based simulation of quantum chemistry.

PMID- 29601759
TI  - Kinetic Theory of Electronic Transport in Random Magnetic Fields.
AB  - We present the theory of quasiparticle transport in perturbatively small
      inhomogeneous magnetic fields across the ballistic-to-hydrodynamic crossover. In
      the hydrodynamic limit, the resistivity rho generically grows proportionally to
      the rate of momentum-conserving electron-electron collisions at large enough
      temperatures T. In particular, the resulting flow of electrons provides a simple
      scenario where viscous effects suppress conductance below the ballistic value.
      This new mechanism for rho?T^{2} resistivity in a Fermi liquid may describe low T
      transport in single-band SrTiO_{3}.

PMID- 29601760
TI  - Accurate Mapping of Multilevel Rydberg Atoms on Interacting Spin-1/2 Particles
      for the Quantum Simulation of Ising Models.
AB  - We study a system of atoms that are laser driven to nD_{3/2} Rydberg states and
      assess how accurately they can be mapped onto spin-1/2 particles for the quantum
      simulation of anisotropic Ising magnets. Using nonperturbative calculations of
      the pair potentials between two atoms in the presence of electric and magnetic
      fields, we emphasize the importance of a careful selection of experimental
      parameters in order to maintain the Rydberg blockade and avoid excitation of
      unwanted Rydberg states. We benchmark these theoretical observations against
      experiments using two atoms. Finally, we show that in these conditions, the
      experimental dynamics observed after a quench is in good agreement with numerical
      simulations of spin-1/2 Ising models in systems with up to 49 spins, for which
      numerical simulations become intractable.

PMID- 29601761
TI  - Visibility-Based Hypothesis Testing Using Higher-Order Optical Interference.
AB  - Many quantum information protocols rely on optical interference to compare data
      sets with efficiency or security unattainable by classical means. Standard
      implementations exploit first-order coherence between signals whose preparation
      requires a shared phase reference. Here, we analyze and experimentally
      demonstrate the binary discrimination of visibility hypotheses based on higher
      order interference for optical signals with a random relative phase. This
      provides a robust protocol implementation primitive when a phase lock is
      unavailable or impractical. With the primitive cost quantified by the total
      detected optical energy, optimal operation is typically reached in the few-photon
      regime.

PMID- 29601762
TI  - Macroscopically Degenerate Exactly Solvable Point in the Spin-1/2 Kagome Quantum
      Antiferromagnet.
AB  - Frustrated quantum magnets are a central theme in condensed matter physics due to
      the richness of their phase diagrams. They support a panoply of phases including
      various ordered states and topological phases. Yet, this problem has defied a
      solution for a long time due to the lack of controlled approximations which make
      it difficult to distinguish between competing phases. Here we report the
      discovery of a special quantum macroscopically degenerate point in the XXZ model
      on the spin-1/2 kagome quantum antiferromagnet for the ratio of Ising to
      antiferromagnetic transverse coupling J_{z}/J=-1/2. This point is proximate to
      many competing phases explaining the source of the complexity of the phase
      diagram. We identify five phases near this point including both spin-liquid and
      broken-symmetry phases and give evidence that the kagome Heisenberg
      antiferromagnet is close to a transition between two phases.

PMID- 29601763
TI  - Switching a Perpendicular Ferromagnetic Layer by Competing Spin Currents.
AB  - An ultimate goal of spintronics is to control magnetism via electrical means. One
      promising way is to utilize a current-induced spin-orbit torque (SOT) originating
      from the strong spin-orbit coupling in heavy metals and their interfaces to
      switch a single perpendicularly magnetized ferromagnetic layer at room
      temperature. However, experimental realization of SOT switching to date requires
      an additional in-plane magnetic field, or other more complex measures, thus
      severely limiting its prospects. Here we present a novel structure consisting of
      two heavy metals that delivers competing spin currents of opposite spin indices.
      Instead of just canceling the pure spin current and the associated SOTs as one
      expects and corroborated by the widely accepted SOTs, such devices manifest the
      ability to switch the perpendicular CoFeB magnetization solely with an in-plane
      current without any magnetic field. Magnetic domain imaging reveals selective
      asymmetrical domain wall motion under a current. Our discovery not only paves the
      way for the application of SOT in nonvolatile technologies, but also poses
      questions on the underlying mechanism of the commonly believed SOT-induced
      switching phenomenon.

PMID- 29601764
TI  - Possible Many-Body Localization in a Long-Lived Finite-Temperature Ultracold
      Quasineutral Molecular Plasma.
AB  - We argue that the quenched ultracold plasma presents an experimental platform for
      studying the quantum many-body physics of disordered systems in the long-time and
      finite energy-density limits. We consider an experiment that quenches a plasma of
      nitric oxide to an ultracold system of Rydberg molecules, ions, and electrons
      that exhibits a long-lived state of arrested relaxation. The qualitative features
      of this state fail to conform with classical models. Here, we develop a
      microscopic quantum description for the arrested phase based on an effective many
      body spin Hamiltonian that includes both dipole-dipole and van der Waals
      interactions. This effective model appears to offer a way to envision the
      essential quantum disordered nonequilibrium physics of this system.

PMID- 29601765
TI  - Edge-Mode Lasing in 1D Topological Active Arrays.
AB  - We report the first observation of lasing topological edge states in a 1D Su
      Schrieffer-Heeger active array of microring resonators. We show that the
      judicious use of non-Hermiticity can promote single edge-mode lasing in such
      arrays. Our experimental and theoretical results demonstrate that, in the
      presence of chiral-time symmetry, this non-Hermitian topological structure can
      experience phase transitions that are dictated by a complex geometric phase. Our
      work may pave the way towards understanding the fundamental aspects associated
      with the interplay among non-Hermiticity, nonlinearity, and topology in active
      systems.

PMID- 29601766
TI  - On-Demand Generation of Neutral and Negatively Charged Silicon-Vacancy Centers in
      Diamond.
AB  - Point defects in wide-band-gap semiconductors are emerging as versatile resources
      for nanoscale sensing and quantum information science, but our understanding of
      the photoionization dynamics is presently incomplete. Here, we use two-color
      confocal microscopy to investigate the dynamics of charge in type 1b diamond
      hosting nitrogen-vacancy (NV) and silicon-vacancy (SiV) centers. By examining the
      nonlocal fluorescence patterns emerging from local laser excitation, we show
      that, in the simultaneous presence of photogenerated electrons and holes, SiV
      (NV) centers selectively transform into the negative (neutral) charge state.
      Unlike NVs, 532 nm illumination ionizes SiV^{-} via a single-photon process, thus
      hinting at a comparatively shallower ground state. In particular, slower
      ionization rates at longer wavelengths suggest the latter lies approximately ~1.9
      eV below the conduction band minimum. Building on the above observations, we
      demonstrate on-demand SiV and NV charge initialization over large areas via green
      laser illumination of variable intensity.

PMID- 29601767
TI  - Demonstration of Cascaded Modulator-Chicane Microbunching of a Relativistic
      Electron Beam.
AB  - We present results of an experiment showing the first successful demonstration of
      a cascaded microbunching scheme. Two modulator-chicane prebunchers arranged in
      series and a high power mid-IR laser seed are used to modulate a 52 MeV electron
      beam into a train of sharp microbunches phase locked to the external drive laser.
      This configuration is shown to greatly improve matching of the beam into the
      small longitudinal phase space acceptance of short-wavelength accelerators. We
      demonstrate trapping of nearly all (96%) of the electrons in a strongly tapered
      inverse free-electron laser accelerator, with an order-of-magnitude reduction in
      injection losses compared to the classical single-buncher scheme. These results
      represent a critical advance in laser-based longitudinal phase space
      manipulations and find application in high gradient advanced acceleration as well
      as in high peak and average power coherent radiation sources.

PMID- 29601768
TI  - Unusual Crystallization Behavior Close to the Glass Transition.
AB  - Using molecular simulations, we shed light on the mechanism underlying crystal
      nucleation in metal alloys and unravel the interplay between crystal nucleation
      and glass transition, as the conditions of crystallization lie close to this
      transition. While decreasing the temperature of crystallization usually results
      in a lower free energy barrier, we find an unexpected reversal of behavior for
      glass-forming alloys as the temperature of crystallization approaches the glass
      transition. For this purpose, we simulate the crystallization process in two
      glass-forming Copper alloys, Ag_{6}Cu_{4}, which has a positive heat of mixing,
      and CuZr, characterized by a large negative heat of mixing. Our results allow us
      to identify this unusual behavior as directly correlated with a nonmonotonic
      temperature dependence for the formation energy of connected icosahedral
      structures, which are incompatible with crystalline order and impede the
      development of the crystal nucleus, leading to an unexpectedly larger free energy
      barrier at low temperature. This, in turn, promotes the formation of a
      predominantly closed-packed critical nucleus, with fewer defects, thereby
      suggesting a new way to control the structure of the crystal nucleus, which is of
      key importance in catalysis.

PMID- 29601769
TI  - Acoustic Purcell Effect for Enhanced Emission.
AB  - We observe that our experimentally measured emission power enhancement of a
      speaker inside a previously proposed metacavity agrees with our numerically
      calculated enhancement of the density of states (DOS) of the source-cavity
      system. We interpret the agreement by formulating a relation between the emitted
      sound power and the acoustic DOS. The formulation is an analog to Fermi's golden
      rule in quantum emission. The formulation complements the radiation impedance
      theory in traditional acoustics for describing sound emission. Our study bridges
      the gap between acoustic DOS and the acoustic Purcell effect for sound emission
      enhancement.

PMID- 29601770
TI  - Charge Order and Superconductivity in Underdoped YBa_{2}Cu_{3}O_{7-delta} under
      Pressure.
AB  - In underdoped cuprates, an incommensurate charge density wave (CDW) order is
      known to coexist with superconductivity. A dip in T_{c} at the hole doping level
      where the CDW is strongest (n_{p}?0.12) suggests that CDW order may suppress
      superconductivity. We investigate the interplay of charge order with
      superconductivity in underdoped YBa_{2}Cu_{3}O_{7-delta} by measuring the
      temperature dependence of the Hall coefficient R_{H}(T) at high magnetic field
      and at high hydrostatic pressure. We find that, although pressure increases T_{c}
      by up to 10 K at 2.6 GPa, it has very little effect on R_{H}(T). This suggests
      that pressure, at these levels, only weakly affects the CDW and that the increase
      in T_{c} with pressure cannot be attributed to a suppression of the CDW. We
      argue, therefore, that the dip in T_{c} at n_{p}?0.12 at ambient pressure is
      probably not caused by the CDW formation.

PMID- 29601771
TI  - Comment on "Continuum Lowering and Fermi-Surface Rising in Strongly Coupled and
      Degenerate Plasmas".

PMID- 29601772
TI  - Higgs Mode in the d-Wave Superconductor Bi_{2}Sr_{2}CaCu_{2}O_{8+x} Driven by an
      Intense Terahertz Pulse.
AB  - We investigate the terahertz (THz)-pulse-driven nonlinear response in the d-wave
      cuprate superconductor Bi_{2}Sr_{2}CaCu_{2}O_{8+x} (Bi2212) using a THz pump near
      infrared probe scheme in the time domain. We observe an oscillatory behavior of
      the optical reflectivity that follows the THz electric field squared and is
      markedly enhanced below T_{c}. The corresponding third-order nonlinear effect
      exhibits both A_{1g} and B_{1g} symmetry components, which are decomposed from
      polarization-resolved measurements. A comparison with a BCS calculation of the
      nonlinear susceptibility indicates that the A_{1g} component is associated with
      the Higgs mode of the d-wave order parameter.

PMID- 29601773
TI  - Strongly gamma-Deformed N=4 Supersymmetric Yang-Mills Theory as an Integrable
      Conformal Field Theory.
AB  - We demonstrate by explicit multiloop calculation that gamma-deformed planar N=4
      supersymmetric Yang-Mills (SYM) theory, supplemented with a set of double-trace
      counterterms, has two nontrivial fixed points in the recently proposed double
      scaling limit, combining vanishing 't Hooft coupling and large imaginary
      deformation parameter. We provide evidence that, at the fixed points, the theory
      is described by an integrable nonunitary four-dimensional conformal field theory.
      We find a closed expression for the four-point correlation function of the
      simplest protected operators and use it to compute the exact conformal data of
      operators with arbitrary Lorentz spin. We conjecture that both conformal symmetry
      and integrability should survive in gamma-deformed planar N=4 SYM theory for
      arbitrary values of the deformation parameters.

PMID- 29601774
TI  - Gravitational-Wave Luminosity of Binary Neutron Stars Mergers.
AB  - We study the gravitational-wave peak luminosity and radiated energy of
      quasicircular neutron star mergers using a large sample of numerical relativity
      simulations with different binary parameters and input physics. The peak
      luminosity for all the binaries can be described in terms of the mass ratio and
      of the leading-order post-Newtonian tidal parameter solely. The mergers resulting
      in a prompt collapse to black hole have the largest peak luminosities. However,
      the largest amount of energy per unit mass is radiated by mergers that produce a
      hypermassive neutron star or a massive neutron star remnant. We quantify the
      gravitational-wave luminosity of binary neutron star merger events, and set upper
      limits on the radiated energy and the remnant angular momentum from these events.
      We find that there is an empirical universal relation connecting the total
      gravitational radiation and the angular momentum of the remnant. Our results
      constrain the final spin of the remnant black hole and also indicate that stable
      neutron star remnant forms with super-Keplerian angular momentum.

PMID- 29601775
TI  - Directional Dicke Subradiance with Nonclassical and Classical Light Sources.
AB  - We investigate Dicke subradiance of N>=2 distant quantum sources in free space,
      i.e., the spatial emission patterns of spontaneously radiating noninteracting
      multilevel atoms or multiphoton sources, prepared in totally antisymmetric
      states. We find that the radiated intensity is marked by a full suppression of
      spontaneous emission in particular directions. In resemblance to the analogous,
      yet inverted, superradiant emission profiles of N distant two-level atoms
      prepared in symmetric Dicke states, we call the corresponding emission patterns
      directional Dicke subradiance. We further derive that higher-order intensity
      correlations of the light emitted by statistically independent thermal light
      sources display the same directional Dicke subradiant behavior and show that it
      stems from the same interference phenomenon as in the case of quantum sources. We
      finally present measurements of directional Dicke subradiance for N=2,...,5
      distant thermal light sources corroborating the theoretical findings.

PMID- 29601776
TI  - Directional Sensitivity in Light-Mass Dark Matter Searches with Single-Electron
      Resolution Ionization Detectors.
AB  - We propose a method using solid state detectors with directional sensitivity to
      dark matter interactions to detect low-mass weakly interacting massive particles
      (WIMPs) originating from galactic sources. In spite of a large body of literature
      for high-mass WIMP detectors with directional sensitivity, no available technique
      exists to cover WIMPs in the mass range <1  GeV/c^{2}. We argue that single
      electron-resolution semiconductor detectors allow for directional sensitivity
      once properly calibrated. We examine the commonly used semiconductor material
      response to these low-mass WIMP interactions.

PMID- 29601777
TI  - A comparison of manual counting of rabbit reticulocytes with ADVIA 2120i analyzer
      counting.
AB  - We compared manual counting of reticulocytes in rabbits with automatic counting
      using an ADVIA 2120i analyzer. Reproducibility and the influence of different
      anticoagulants (EDTA and Li-heparin) were also examined. Blood samples of 331
      rabbits (method comparison, n = 289; reproducibility, n = 33; comparison of
      anticoagulants, n = 9) were tested. The reticulocyte numbers of each specimen
      were manually determined twice for method comparison. Passing-Bablok regressions,
      Bland-Altman plots, and the coefficient of variation (CV) were used to evaluate
      statistical significance. Good correlation (rs = 0.81) was observed between
      manual reticulocyte counting (groups 1-4) and the ADVIA 2120i. Quantification
      with the ADVIA 2120i was reproducible for relative reticulocyte numbers (EDTA, CV
      = 4.24%; Li-heparin, CV = 3.63%) and absolute reticulocyte numbers (EDTA, CV =
      5.64%; Li-heparin, CV = 3.81%). The absolute and relative reticulocyte numbers
      were significantly higher in Li-heparin samples than in EDTA samples (absolute, p
      = 0.009; relative, p = 0.016). The ADVIA 2120i is suitable for counting
      reticulocytes in rabbit blood samples, but reticulocyte numbers are higher by
      manual counting than by ADVIA 2120i counting. Therefore, microscopic confirmation
      of quantifications is recommended when high numbers of reticulocytes are
      observed. The anticoagulant of choice is EDTA.

PMID- 29601778
TI  - Frequency of Equus caballus papillomavirus in equine aural plaques.
AB  - Despite the reported association between aural plaques and the presence of Equus
      caballus papillomavirus (EcPV), there are few data regarding the distribution of
      viral types in different geographic regions or possible correlations for
      different papillomaviruses and lesion characteristics. We detected the presence
      and frequency of EcPV (1-7) DNA in aural plaque biopsies of horses from different
      regions of Brazil and identified the patterns of these infections or coinfections
      and their possible association with lesion severity. A total of 108 aural plaque
      biopsies from horses in the 5 geopolitical regions of Brazil were examined. We
      performed PCR to detect EcPV DNA in the biopsies. At least 1 type of EcPV was
      detected in 97% of the samples. EcPV coinfection was observed in 59% of the
      samples. Compared to the other viruses, EcPV-4 was found at the highest frequency
      in coinfection (84%) or individually identified (32%). EcPV-2 and -7 were not
      detected. No significant association was found between lesion characteristics
      (type and distribution) and either the viral type detected or the presence of
      coinfection. EcPV is widely distributed in Brazil, both isolated and in
      coinfection; the viral type does not appear to influence the clinical
      characteristics of equine aural plaques.

PMID- 29601779
TI  - Blastomyces dermatitidis pneumonia in a llama.
AB  - A 20-y-old female llama ( Lama glama) was euthanized after a history of chronic
      dyspnea and osteoarthritis. At autopsy, the lungs were covered by clear
      gelatinous material and expanded by firm, variably discrete, tan-white nodules up
      to 8 cm diameter containing tan-white, viscous material. The tracheobronchial
      lymph nodes were firm and enlarged up to 6 * 4 * 3 cm; the thoracic aorta and
      carotid arteries were lined by hard, tan-white, mineralized intimal plaques.
      Histologic examination of lung revealed numerous 10-20 MUm diameter yeasts with
      clear 1-2 MUm thick double-contoured walls, central basophilic nuclei, and
      frequent broad-based budding, consistent with Blastomyces dermatitidis. DNA
      sequencing confirmed the diagnosis. B. dermatitidis should be considered in the
      differential diagnosis of pulmonary disease in llamas.

PMID- 29601780
TI  - Development and validation of a real-time PCR specific for the leukotoxin gene of
      Bibersteinia trehalosi.
AB  - A real-time PCR assay for the leukotoxin gene of Bibersteinia trehalosi was
      developed and validated to better identify this pathogen, which is a cause of
      respiratory disease in bighorn sheep. The specificity of the PCR primers was
      evaluated with DNA from 59 known isolates of the Pasteurellaceae family. For
      validation, 162 field samples were compared using both the new assay and an
      indirect method using 2 sets of published protocols. The real-time PCR assay was
      found to be specific for the leukotoxin gene of B. trehalosi and provides a rapid
      and direct approach for detecting leukotoxin-producing forms of this organism
      from samples containing mixed species of leukotoxin-positive Pasteurellaceae.

PMID- 29601781
TI  - Cardiac fibroblast-specific p38alpha MAP kinase promotes cardiac hypertrophy via
      a putative paracrine interleukin-6 signaling mechanism.
AB  - Recent studies suggest that cardiac fibroblast-specific p38alpha MAPK contributes
      to the development of cardiac hypertrophy, but the underlying mechanism is
      unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38alpha
      knockout (KO) mouse line to characterize the role of fibroblast p38alpha in
      modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial
      injury was induced in tamoxifen-treated Cre-positive p38alpha KO mice or control
      littermates via chronic infusion of the beta-adrenergic receptor agonist
      isoproterenol. Cardiac function was assessed by pressure-volume conductance
      catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular,
      and molecular levels. Isoproterenol infusion in control mice promoted overt
      cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end
      systolic volume, increased cardiac weight index, increased cardiomyocyte area,
      increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy
      associated microRNAs). Fibroblast-specific p38alpha KO mice exhibited marked
      protection against myocardial injury, with isoproterenol-induced alterations in
      cardiac function, histology, and molecular markers all being attenuated. In vitro
      mechanistic studies determined that cardiac fibroblasts responded to damaged
      myocardium by secreting several paracrine factors known to induce cardiomyocyte
      hypertrophy, including IL-6, whose secretion was dependent upon p38alpha
      activity. In conclusion, cardiac fibroblast p38alpha contributes to cardiomyocyte
      hypertrophy and cardiac dysfunction, potentially via a mechanism involving
      paracrine fibroblast-to-myocyte IL-6 signaling.-Bageghni, S. A., Hemmings, K. E.,
      Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J.,
      Turner, N. A. Cardiac fibroblast-specific p38alpha MAP kinase promotes cardiac
      hypertrophy via a putative paracrine interleukin-6 signaling mechanism.

PMID- 29601782
TI  - Hepatic PHD2/HIF-1alpha axis is involved in postexercise systemic energy
      homeostasis.
AB  - Exercise plays an important role in the prevention and treatment of chronic liver
      disease and associated metabolic disorders. A single bout of exercise induces
      tissue blood flow redistribution, which decreases splanchnic circulation and
      leads to physiologic hypoxia in the gastrointestinal system and liver. The
      transcription factor, hypoxia inducible factor-1alpha (HIF-1alpha), and its
      regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to
      oxygen flux by regulating downstream gene expression levels in the liver. We
      hypothesized that exercise increases the HIF-1alpha levels in the liver, and that
      the hepatic PHD2/HIF-1alpha axis is involved in postexercise restoration of
      systemic energy homeostasis. Through constant O2 consumption, CO2 production,
      food and water intake, and physical activity detection with metabolic chambers,
      we observed that one 30-min session of swimming exercise enhances systemic energy
      metabolism in mice. By using the noninvasive bioluminescence imaging ROSA26
      oxygen-dependent domain Luc mouse model, we reveal that exercise increases in
      vivo HIFalpha levels in the liver. Intraperitoneal injections of the PHD
      inhibitor, dimethyloxalylglycine, mimicked exercise-induced HIFalpha increase,
      whereas the HIF-1alpha inhibitor, PX-478, blocked this effect. We next
      constructed liver-specific knockout (LKO) mouse models with albumin- Cre
      mediated, hepatocyte-specific Hif1a and Phd2 deletion. Compared with their
      controls, Hif1a-LKO and Phd2-LKO mice exhibited distinct patterns of hepatic
      metabolism-related gene expression profiles. Moreover, Hif1a-LKO mice failed to
      restore systemic energy homeostasis after exercise. In conclusion, the current
      study demonstrates that a single bout of exercise disrupts systemic energy
      homeostasis, increasing the HIF-1alpha levels in the liver. These findings also
      provide evidence that the hepatic PHD2/HIF-1alpha axis is involved in
      postexercise systemic metabolic homeostasis.-Luo, B., Xiang, D., Wu, D., Liu, C.,
      Fang, Y., Chen, P., Hu, Y.-P. Hepatic PHD2/HIF-1alpha axis is involved in
      postexercise systemic energy homeostasis.

PMID- 29601783
TI  - Editorial Comment.

PMID- 29601784
TI  - Editorial Comment.

PMID- 29601785
TI  - Reply by Authors.

PMID- 29601786
TI  - Self-assembly of Mutant Huntingtin Exon-1 Fragments into Large Complex Fibrillar
      Structures Involves Nucleated Branching.
AB  - Huntingtin (HTT) fragments with extended polyglutamine tracts self-assemble into
      amyloid-like fibrillar aggregates. Elucidating the fibril formation mechanism is
      critical for understanding Huntington's disease pathology and for developing
      novel therapeutic strategies. Here, we performed systematic experimental and
      theoretical studies to examine the self-assembly of an aggregation-prone N
      terminal HTT exon-1 fragment with 49 glutamines (Ex1Q49). Using high-resolution
      imaging techniques such as electron microscopy and atomic force microscopy, we
      show that Ex1Q49 fragments in cell-free assays spontaneously convert into large,
      highly complex bundles of amyloid fibrils with multiple ends and fibril branching
      points. Furthermore, we present experimental evidence that two nucleation
      mechanisms control spontaneous Ex1Q49 fibrillogenesis: (1) a relatively slow
      primary fibril-independent nucleation process, which involves the spontaneous
      formation of aggregation-competent fibrillary structures, and (2) a fast
      secondary fibril-dependent nucleation process, which involves nucleated branching
      and promotes the rapid assembly of highly complex fibril bundles with multiple
      ends. The proposed aggregation mechanism is supported by studies with the small
      molecule O4, which perturbs early events in the aggregation cascade and delays
      Ex1Q49 fibril assembly, comprehensive mathematical and computational modeling
      studies, and seeding experiments with small, preformed fibrillar Ex1Q49
      aggregates that promote the assembly of amyloid fibrils. Together, our results
      suggest that nucleated branching in vitro plays a critical role in the formation
      of complex fibrillar HTT exon-1 aggregates with multiple ends.

PMID- 29601788
TI  - Isolated Light Chain Amyloidosis Involving the Parotid Gland: A Case Report.
AB  - Amyloidosis in the parotid gland is rare and is usually associated with systemic
      amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. We
      present a case of localized light chain amyloidosis of the parotid gland without
      systemic involvement. A 70-year-old woman presented with an asymptomatic swelling
      of the right parotid region. The findings of a physical examination, hematologic
      and biochemical investigations, imaging, and cytology were inconclusive. The
      patient underwent an extracapsular dissection of the right parotid gland.
      Histologic analysis showed that the tissue of the right parotid gland mostly
      consisted of amyloid deposition. The amyloid stained with antibodies to lambda
      light chains. Additional investigations showed no systemic involvement. The
      patient is asymptomatic 5 months after surgery. Clinicians should be aware of the
      possibility of localized amyloid light chain amyloidosis in the parotid gland,
      especially if magnetic resonance imaging, computed tomography imaging, and
      ultrasound findings are inconclusive, and they should recognize, evaluate, and
      treat it accordingly.

PMID- 29601789
TI  - Comparative Evaluation of Healing Pattern After Surgical Excision of Oral Mucosal
      Lesions by Using Platelet-Rich Fibrin (PRF) Membrane and Collagen Membrane as
      Grafting Materials-A Randomized Clinical Trial.
AB  - PURPOSE: To compare the healing potential of platelet-rich fibrin (PRF) and
      collagen membranes in oral mucosal healing. MATERIALS AND METHODS: Thirty
      patients with oral premalignant lesions were randomly included in the study and
      divided in groups A and B. After excising the lesions under local anesthesia,
      patients in groups A and B underwent grafting with the PRF membrane and the
      collagen membrane, respectively. Patients were evaluated at postoperative days 7,
      15, 30, and 60 for pain, healing, and complications, such as recurrence,
      fibrosis, scar hypertrophy, and loss of vestibular depth. RESULTS: In group A,
      66.66% of patients reported substantially less pain postoperatively at 15-day
      follow-up than those in group B. At 30-day follow-up, 86.66% of patients in group
      A reported no pain versus 60% in group B. Pain scores were similar at 7- and 60
      day follow-ups. Healing was accelerated in group A at 15- and 30-day follow-ups,
      but was the same on day 60. Complications, such as fibrosis, loss of vestibular
      depth, and scar hypertrophy, were seen in group B. Recurrence was seen in 1
      patient in group A at 60-day follow-up. CONCLUSION: PRF proved superior to
      collagen membrane for grafting of oral mucosal surgical defects. However, further
      study with larger samples is required to prove its efficacy.

PMID- 29601787
TI  - Prevalence of the apolipoprotein E epsilon4 allele in amyloid beta positive
      subjects across the spectrum of Alzheimer's disease.
AB  - INTRODUCTION: Apolipoprotein E (APOE) epsilon4 is the major genetic risk factor
      for Alzheimer's disease (AD), but its prevalence is unclear because earlier
      studies did not require biomarker evidence of amyloid beta (Abeta) pathology.
      METHODS: We included 3451 Abeta+ subjects (853 AD-type dementia, 1810 mild
      cognitive impairment, and 788 cognitively normal). Generalized estimating
      equation models were used to assess APOE epsilon4 prevalence in relation to age,
      sex, education, and geographical location. RESULTS: The APOE epsilon4 prevalence
      was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in
      cognitively normal, and it decreased with advancing age in Abeta+ cognitively
      normal and Abeta+ mild cognitive impairment (P < .05) but not in Abeta+ AD
      dementia (P = .66). The prevalence was highest in Northern Europe but did not
      vary by sex or education. DISCUSSION: The APOE epsilon4 prevalence in AD was
      higher than that in previous studies, which did not require presence of Abeta
      pathology. Furthermore, our results highlight disease heterogeneity related to
      age and geographical location.

PMID- 29601790
TI  - Is Visceral Leishmaniasis the same in HIV-coinfected adults?
AB  - INTRODUCTION: Visceral Leishmaniasis is the most severe form of disease caused by
      the Leishmania donovani complex, with significant morbidity and mortality in
      developing countries. Worse outcomes occur among HIV-positive individuals
      coinfected with Leishmania. It is unclear, however, if there are significant
      differences on presentation between Visceral Leishmaniasis patients with or
      without HIV coinfection. METHODS: We reviewed medical records from adult patients
      with Visceral Leishmaniasis treated at a reference healthcare center in Fortaleza
      - Ceara, Brazil, from July 2010 to December 2013. Data from HIV-coinfected
      patients have been abstracted and compared to non-HIV controls diagnosed with
      Visceral Leishmaniasis in the same period. RESULTS: Eighty one HIV-infected
      patients and 365 controls were enrolled. The diagnosis in HIV patients took
      significantly longer, with higher recurrence and death rates. Kala-azar's
      classical triad (fever, constitutional symptoms and splenomegaly) was less
      frequently observed in Visceral Leishmaniasis-HIV patients, as well as jaundice
      and edema, while diarrhea was more frequent. Laboratory features included lower
      levels of hemoglobin, lymphocyte counts and liver enzymes, as well as higher
      counts of blood platelets and eosinophils. HIV-infected patients were diagnosed
      mainly through amastigote detection on bone marrow aspirates and treated more
      often with amphotericin B formulations, whereas in controls, rK39 was the main
      diagnostic tool and pentavalent antimony was primarily used for treatment.
      CONCLUSIONS: Clinical and laboratory presentation of Visceral Leishmaniasis in
      HIV-coinfected patients may differ from classic kala-azar, and these differences
      may be, in part, responsible for the delay in diagnosing and treating
      leishmaniasis, which might lead to worse outcomes.

PMID- 29601792
TI  - Effects of iridoid-anthocyanin extract of Cornus mas L. on hematological
      parameters, population and proliferation of lymphocytes during experimental
      infection of mice with Trichinella spiralis.
AB  - The influence of iridoid-anthocyanin aqueous extract of cornelian cherry fruits
      (CM) on hematological parameters, lymphocyte subsets and proliferation during
      Trichinella spiralis infection in mice was investigated. CM (100 mg/kg) was
      administered orally to T. spiralis-infected mice six times within a period
      encompassing three days prior to the infection and three days after the infection
      (dai). CM increased the percentage of CD3+, CD4+ cells and CD4+/CD8+ ratio and
      decreased total count of CD8+ and CD19+ splenocytes (5th dai). An increase in
      total count of CD4+, CD3+, CD19+ splenocytes was observed (21st dai). CM elevated
      the percentage of CD4+ cells (7th dai) and CD4+/CD8+ ratio (21st dai) in MLN. CM
      increased (14th dai) and then reduced (21st dai) the percentage of CD8+ MLN
      lymphocytes and decreased total count of MLN CD8+ cells (21st dai) and B cells
      (14th dai). An activation of lymphocyte proliferation in spleen and simultaneous
      decrease in MLN on 5th dai was observed. An increase in red blood cells
      parameters (5th dai) and in leukocyte count (7th dai) was found. A rise in
      platelet count was noticed both on 5th and 7th dai. Moreover, the number of adult
      T. spiralis on 5th dai in mice receiving CM extract was lower than in the control
      mice. These results suggested that iridoid-anthocyanin aqueous extract of CM
      stimulated murine immune response during T. spiralis infection.

PMID- 29601791
TI  - Biofilm production by clinical isolates of Pseudomonas aeruginosa and structural
      changes in LasR protein of isolates non biofilm-producing.
AB  - INTRODUCTION: Biofilm production is an important mechanism for the survival of
      Pseudomonas aeruginosa and its relationship with antimicrobial resistance
      represents a challenge for patient therapeutics. P. aeruginosa is an
      opportunistic pathogen frequently associated to nosocomial infections, especially
      in imunocompromised hosts. OBJECTIVES: Analyze the phenotypic biofilm production
      in P. aeruginosa isolates, describe clonal profiles, and analyze quorum sensing
      (QS) genes and the occurrence of mutations in the LasR protein of non-biofilm
      producing isolates. METHODS: Isolates were tested for biofilm production by
      measuring cells adherence to the microtiter plates. Clonal profile analysis was
      carried out through ERIC-PCR, QS genes were by specific PCR. RESULTS: The results
      showed that 77.5% of the isolates were considered biofilm producers. The results
      of genotyping showed 38 distinct genetic profiles. As for the occurrence of the
      genes, 100% of the isolates presented the lasR, rhlI and rhlR genes, and 97.5%,
      presented the lasI gene. In this study nine isolates were not biofilm producers.
      However, all presented the QS genes. Amplicons related to genes were sequenced in
      three of the nine non-biofilm-producing isolates (all presenting different
      genetic similarity profile) and aligned to the sequences of those genes in P.
      aeruginosa strain PAO1 (standard biofilm-producing strain). Alignment analysis
      showed an insertion of three nucleotides (T, C and G) causing the addition of an
      amino acid valine in the sequence of the LasR protein, in position 53.
      CONCLUSION: The modeling of the resulting LasR protein showed a conformational
      change in its structure, suggesting that this might be the reason why these
      isolates are unable to produce biofilm.

PMID- 29601793
TI  - Novel univariate and multivariate regression methods for the simultaneous
      analysis of ternary mixture of 1, 4-benzodiazepines in dosage forms and human
      urine.
AB  - In this paper, novel univariate and multivariate regression model updating
      methods were developed and validated for the simultaneous determination of
      ternary mixture of bromazepam, diazepam and clonazepam. The univariate methods
      used are the mean centering of ratio spectrophotometric method and iso-absorptive
      point coupled with ratio-subtraction and ratio difference spectrophotometric
      method. Linearity, ranges, precision and accuracy of these methods were
      determined. The multivariate methods adopted are the principal component
      regression and partial least-squares. These models were estimated using nineteen
      mixtures as calibration set and six mixtures as validation set. The minimum root
      square error of predication were 0.1215 and 0.0568 for BMZ, 0.0598 and 0.0712 for
      DIZ and 0.0867 and 0.0753 for CNP by PLS and PCR respectively. PCR and PLS
      methods were successfully applied for the analysis of BMZ, DIZ and CNP in their
      dosage forms. Content uniformity testing of the studied pharmaceutical tablets by
      PLS and PCR was also determined. MCR, IPRSRD and PLS model updating enabled the
      determination of BMZ, DIZ and CNP in spiked human urine. Moreover, PLS model
      updating was applied to drug-dissolution rate testing of BMZ and DIZ in their
      commercial tablets. The obtained results were statistically compared with those
      obtained by reported methods giving a conclusion that there is no significant
      difference regarding accuracy and precision.

PMID- 29601795
TI  - Genitourinary syndrome of menopause: corrections and comments by a gynecologist.

PMID- 29601794
TI  - Voxelotor (GBT440) produces interference in measurements of hemoglobin S.

PMID- 29601796
TI  - Prevention of adverse pulmonary, neurological, and ocular perinatal outcomes by
      supplementing omega-3 fatty acids during pregnancy.

PMID- 29601797
TI  - How shall we transfuse Hippolyta? The same way whether on or off the battlefield.

PMID- 29601798
TI  - Reply.

PMID- 29601799
TI  - The three branches of the unfolded protein response exhibit differential
      significance in breast cancer growth and stemness.
AB  - The unfolded protein response (UPR) is widely activated in cancers. The mammalian
      UPR encompasses three signaling branches, namely inositol-requiring enzyme-1alpha
      (IRE1alpha), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and
      activating transcription factor 6alpha (ATF6alpha). The functional significance
      of each branch in tumorigenesis is incompletely understood, especially in cancer
      stem cells (CSCs). Here, we report that inhibition and silencing of the three UPR
      sensors has differential effects on breast cancer growth and the CSC population.
      The levels of PERK and ATF6alpha strongly correlate with the expression of sex
      determining region Y (SRY)-box 2 (SOX2), a pluripotency regulator, in human
      breast cancer tissues. UPR activation is also elevated in the CSC-enriched
      mammospheres. Inhibition of the UPR sensors or excess ER stress markedly reduces
      the formation and maintenance of mammospheres, suggesting that an appropriate
      level of UPR activation is critical for the CSC survival. Mechanistically,
      transcription factors from UPR and pluripotency pathways interact and
      reciprocally influence each other. A transcription modulator, CCAAT-enhancer
      binding protein delta (C/EBPdelta), interacts with pluripotency regulator, SOX2,
      and UPR transcription factors, thus likely serving as a link to coordinate UPR
      and pluripotency maintenance in CSCs. Our findings demonstrate that UPR is
      critical for both cancer growth and pluripotency, and highlight the differential
      role and complexity of the three UPR branches in tumorigenesis.

PMID- 29601800
TI  - Overexpression of miR-182 inhibits ossification of ligamentum flavum cells by
      targeting NAMPT.
AB  - Ossification of the ligamentum flavum (OLF) is a debilitating disease resulting
      from the development of ectopic bone formation, which leads to the compression of
      the spinal cord. Nicotinamide phosphoribosyltransferase (NAMPT) was found to be
      upregulated and microRNA-182 (miR-182) was downregulated in OLF tissue. We
      investigated the effects of NAMPT and miR-182 expression in OLF cells and the
      influence on proteins associated with osteogenic differentiation. MiR-182
      overexpression inhibited NAMPT, RUNX2, OCN and OPN mRNA and protein expression in
      OLF cells. Alkaline phosphatase (ALP) assay and Alizarin red staining confirmed
      reduced levels of osteogenic differentiation and mineralized nodule formation.
      Knockdown of NAMPT and the NAMPT inhibitor FK866 also inhibits RUNX2, OCN and OPN
      mRNA expression and protein levels, whereas overexpression of NAMPT promotes the
      expression of RUNX2, OCN and OPN and the generation of bone nodules. Dual
      luciferase reporter assays revealed that miR-182 directly targets NAMPT and
      downregulates its expression. Transfection of OLF cells with miR-182
      downregulated NAMPT and suppressed the regulation of RUNX2, OCN, and OPN by NAMPT
      overexpression. Overall, these data demonstrate that miR-182 suppresses OLF by
      downregulating NAMPT.

PMID- 29601801
TI  - The accuracy of transcutaneous bilirubinometer measurements to identify the
      hyperbilirubinemia in outpatient newborn population.
AB  - OBJECTIVES: To assess the ability of transcutaneous bilirubinometer for
      prediction total serum bilirubin levels in newborn infants after hospital
      discharge. METHODS: Newborn infants requiring total serum bilirubin (TSB) level
      measurement during an outpatient follow-up visit were included into the study.
      Transcutaneous bilirubin (TcB) measurement was carried out using JH20-1C (Ningbo
      David, China) transcutaneous jaundice detector and total serum bilirubin was
      simultaneously determined by direct spectrophotometry. The agreement between
      paired TSB and TcB measurements were assessed by Bland-Altman plot and Deming
      regression analysis. Predictive indices were also identified in different TcB cut
      off values for TSB levels of 222, 256 and 291 MUmol/L. RESULTS: A total of 271
      paired TcB and TSB measurements were obtained from 218 newborn infants. 40.2% had
      an age of above 7 days at measurement time. The mean difference (95% CI) between
      TcB and TSB values was -1.7 (-5.4 to 2.1) MUmol/L. For TSB levels of at least 256
      and 291 MUmol/L, a TcB cut-off of 222 MUmol/L shows sensitivity of 90.6% and
      100%, respectively. It was also determined that 39.4% of TSB measurements could
      be avoided when using TcB cut-off value of 222 MUmol/L. CONCLUSION: The
      measurement of TcB with JH20-1C seems to be a reliable screening method for
      hyperbilirubinemia in the outpatient population when used a TcB cut-off of 222
      MUmol/L. The use of transcutaneous bilirubinometer could reduce the number of
      invasive blood sampling for the determination serum bilirubin.

PMID- 29601802
TI  - Impact of an Interdisciplinary Computational Research Section in a Department of
      Medicine: An 8-Year Perspective.

PMID- 29601803
TI  - Eliminating In-Hospital Fecal Occult Blood Testing: Our Experience with
      Disinvestment.

PMID- 29601804
TI  - Follow the Lead: Internal Jugular Vein Thrombosis.

PMID- 29601805
TI  - Adsorption of human serum albumin on functionalized single-walled carbon
      nanotubes reduced cytotoxicity.
AB  - With the potential uses of carbon nanotubes (CNTs) in biomedical and
      biotechnological applications, and the growing concerns about nanotoxicity of
      these engineered nanoparticles, the importance of protein-nanoparticle
      interaction has not been well stressed. In this study, we used both experimental
      and theoretical approaches to investigate the interactions of different
      functionalized single-walled CNTs (SWCNTs) with human serum albumin (HSA). It was
      found that the HSA adsorption capacities of CNTs followed the order carboxylated
      SWCNTs > hydroxylated SWCNTs > amined SWCNTs. The fluorescence intensity of HSA
      was quenched by all of the three SWCNTs in static mode, which was authenticated
      by Stern-Volmer calculations. Our molecular dynamics simulations revealed that
      both atom-atom contact numbers and binding energies between functionalized SWCNTs
      and HSA played critical roles in determining their adsorption capacity, in
      agreement with the experimental findings. Additional cytotoxicity assays revealed
      that coating of carboxylated CNTs with HSA more significantly reduced their
      cytotoxicity than the other two CNTs, in agreement with their protein adsorption
      capacities in vitro. These findings will be helpful to clarify the mechanism of
      interactions of functionalized SWCNTs with human serum proteins, and provide more
      insight into the understanding of how to design the safe nanoparticles by
      preconsideration of their interactions with proteins.

PMID- 29601806
TI  - Remote Ischemic Preconditioning Does Not Prevent White Matter Injury in Neonates.
AB  - BACKGROUND: Remote ischemic preconditioning (RIPC) is a mechanism to protect
      tissues from injury during ischemia and reperfusion. We investigated the
      neuroprotective effects of RIPC in neonates undergoing cardiac surgery. METHODS:
      The outcome was white matter injury (WMI), assessed by the change in volume of
      WMI from preoperative to postoperative brain magnetic resonance imaging (MRI).
      Patients were randomized to RIPC or SHAM. RIPC was induced prior to
      cardiopulmonary bypass by four 5-minute cycles of blood pressure cuff inflation
      to produce ischemia of the lower extremity. For patients randomized to SHAM, the
      cuff was positioned, but not inflated. RESULTS: The study included 67 patients,
      with 33 randomized to RIPC and 34 randomized to SHAM. Preoperative and
      postoperative MRIs were available in 50 patients, including 26 of the 33 RIPC
      patients and 24 of the 34 SHAM patients. There were no differences in baseline
      and operative characteristics for either the overall study group or the group
      with evaluable MRIs. WMI was identified in 28% of the patients preoperatively and
      in 62% postoperatively. There was no difference in the prevalence of WMI by
      treatment group (p > 0.5). RIPC patients had an average change in WMI of 600 mL3,
      and SHAM subjects had an average WMI change of 107 mL3. There was no significant
      difference in the mean value of WMI change between patients who received RIPC and
      those who received SHAM treatments (p = 0.178). CONCLUSIONS: In this randomized,
      blinded clinical trial, there was no evidence that use of RIPC provides
      neuroprotection in neonates undergoing repair of congenital heart defects with
      cardiopulmonary bypass.

PMID- 29601807
TI  - Utility of Site-Specific Biopsy for Diagnosis of Desmoplastic Malignant
      Mesothelioma.
AB  - Desmoplastic malignant mesothelioma (DMM) is a relatively rare histologic subtype
      of malignant pleural mesothelioma (MPM). Among MPMs, the diagnosis of DMM is
      particularly difficult because the tumor is largely composed of dense hyalinized
      fibrous stroma and few malignant cells. We present two cases of DMM, one in a 47
      year-old man and the other in a 64-year-old man. From detailed pathologic
      findings in these two cases, we conclude that cases of DMM that cannot otherwise
      be diagnosed with the use of conventional pleural biopsy, may be diagnosed
      successfully with the use of wedge lung resection.

PMID- 29601808
TI  - Ventricular Septal Dissection After Surgical Repair of Postinfarction Ventricular
      Septal Defect.

PMID- 29601809
TI  - Hatching synchrony is controlled by a two-step mechanism in the migratory locust
      Locusta migratoria (Acrididae: Orthoptera): Roles of vibrational stimuli.
AB  - The eggs of the migratory locust, Locust migratoria, hatch in synchrony from
      their pod. In this study, we examined the mechanism controlling hatching
      synchrony. Two eggs obtained from the same pod hatched in synchrony when kept in
      contact with one another, whereas those separated by a few millimeters hatched
      less synchronously. When a screen separated the eggs, the hatching was even more
      sporadic, indicating that hatching synchrony might be controlled by a two-step
      mechanism. We hypothesize that in the first step the embryos shortly before
      hatching control the time to enter a standby stage using some signal from
      neighboring eggs. The eggs in the standby stage hatch promptly when an additional
      stimulus is received from neighboring eggs. Before this stage, eggs cannot
      respond to that stimulus by hatching but may spontaneously hatch later.
      Introduction of a newly hatched nymph to single eggs 1 or 2 days before hatching
      advanced hatching of these eggs, but hatching occurred only sporadically. Eggs
      kept in contact with other eggs that had been killed by freezing shortly before
      hatching hatched as if they had been kept singly in separate containers,
      providing no evidence for involvement of chemical stimuli in controlling hatching
      synchrony. By contrast, eggs separated by several millimeters hatched as
      synchronously as those kept in contact with one another when they were connected
      by a piece of wire. Furthermore, vibrational stimulation derived from music
      greatly advanced hatching of separately kept eggs; however, hatching synchrony
      was not achieved unless the music started shortly before hatching. These results
      are consistent with the two-step hypothesis and indicated that locust embryos
      used vibrational stimuli from neighboring eggs for synchronous hatching.

PMID- 29601810
TI  - 2',3-dihydroxy-5-methoxybiphenyl suppresses fMLP-induced superoxide anion
      production and cathepsin G release by targeting the beta-subunit of G-protein in
      human neutrophils.
AB  - This study investigates the effect and the underlying mechanism of 2',3-dihydroxy
      5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis
      indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on
      N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst
      and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which
      modulated fMLP-induced respiratory burst were evaluated by an interaction between
      beta subunit of G-protein (Gbeta) with downstream signaling induced by fMLP and
      by immunoblotting analysis of the downstream targets of Gbeta-protein. RIR-2
      inhibited fMLP-induced superoxide anion production (IC50:2.57 +/- 0.22 MUM),
      cathepsin G release (IC50:18.72 +/- 3.76 MUM) and migration in a concentration
      dependent manner. RIR-2 specifically suppresses fMLP-induced Src family kinases
      phosphorylation by inhibiting the interaction between Gbeta-protein with Src
      kinases without inhibiting Src kinases activities, therefore, RIR-2 attenuated
      the downstream targets of Src kinase, such as phosphorylation of Raf/ERK, AKT,
      P38, PLCgamma2, PKC and translocation Tec, p47ph degrees x and P40ph degrees x
      from the cytosol to the inner leaflet of the plasma membrane. Furthermore, RIR-2
      attenuated fMLP-induced intracellular calcium mobilization by inhibiting the
      interaction between Gbeta-protein with PLCbeta2. RIR-2 was not a competitive or
      allosteric antagonist of fMLP. On the contrary, phorbol 12-myristate 13-acetate
      (PMA)-induced phosphorylation of Src, AKT, P38, PKC and membrane localization of
      p47ph degrees x and P40ph degrees x remained unaffected. RIR-2 specifically
      modulates fMLP-mediated neutrophil superoxide anion production and cathepsin G
      release by inhibiting the interaction between Gbeta-protein with downstream
      signaling which subsequently interferes with the activation of intracellular
      calcium, PLCgamma2, AKT, p38, PKC, ERK, p47ph degrees x and p40phox.

PMID- 29601811
TI  - Perineural Invasion in Human Cutaneous Squamous Cell Carcinoma Is Linked to
      Neurotrophins, Epithelial-Mesenchymal Transition, and NCAM1.

PMID- 29601812
TI  - Identification of the key determinant of the transport promiscuity in Na+
      translocating rhodopsins.
AB  - Bacterial Na+-transporting rhodopsins convert solar energy into transmembrane ion
      potential difference. Typically, they are strictly specific for Na+, but some can
      additionally transport H+. To determine the structural basis of cation
      promiscuity in Na+-rhodopsins, we compared their primary structures and found a
      single position that harbors a cysteine in strictly specific Na+-rhodopsins and a
      serine in the promiscuous Krokinobacter eikastus Na+-rhodopsin (Kr2). A Cys253Ser
      variant of the strictly specific Dokdonia sp. PRO95 Na+-rhodopsin (NaR) was
      indeed found to transport both Na+ and H+ in a light-dependent manner when
      expressed in retinal-producing Escherichia coli cells. The dual specificity of
      the NaR variant was confirmed by analysis of its photocycle, which revealed an
      acceleration of the cation-capture step by comparison with the wild-type NaR in a
      Na+-deficient medium. The structural basis for the dependence of the Na+/H+
      specificity in Na+-rhodopsin on residue 253 remains to be determined.

PMID- 29601813
TI  - Effects of cell adhesion motif, fiber stiffness, and cyclic strain on tenocyte
      gene expression in a tendon mimetic fiber composite hydrogel.
AB  - We recently developed a fiber composite consisting of tenocytes seeded onto
      discontinuous fibers embedded within a hydrogel, designed to mimic physiological
      tendon micromechanics of tension and shear. This study examined if cell adhesion
      peptide (DGEA or YRGDS), fiber modulus (50 or 1300 kPa) and/or cyclic strain (5%
      strain, 1 Hz) influenced bovine tenocyte gene expression. Ten genes were analyzed
      and none were sensitive to peptide or fiber modulus in the absence of cyclic
      tensile strain. Genes associated with tendon (SCX and TNMD), collagens (COL1A1,
      COL3A1, COL11A1), and matrix remodelling (MMP1, MMP2, and TIMP3) were insensitive
      to cyclic strain. Contrarily, cyclic strain up-regulated IL6 by 30-fold and MMP3
      by 10-fold in soft YRGDS fibers. IL6 expression in soft YRGDS fibers was 5.7 and
      3.3-fold greater than in soft DGEA fibers and stiff RGD fibers, respectively,
      under cyclic strain. Our findings suggest that changes in the surrounding matrix
      can influence catabolic genes in tenocytes when cultured in a complex strain
      environment mimicking that of tendon, while having minimal effects on tendon and
      homeostatic genes.

PMID- 29601814
TI  - Isolation and identification of two new alleles of STICHEL in Arabidopsis.
AB  - Plant trichome has long been selected as a model system to study the regulatory
      mechanism during cell development due to its unique growth characteristics. In an
      effort to explore new components that contribute to trichome development, we
      performed large-scale forward genetic screening in Arabidopsis, and found two
      recessive mutants with significant trichome branching defects, both of which
      display one branched trichomes. After map-based cloning, genetic complementation
      experiments, we confirmed that they are new alleles of STICHEL (STI) that has
      been reported to act as a key regulator of trichome branching. The predicted
      product of STI gene is comprised by three functional domains including a large
      domain with sequence similarity to eubacterial DNA polymerase III gamma-subunit
      in the middle, two PEST domains in the N terminal, and two nuclear localization
      signals (NLS) at the very N terminal and C terminal, respectively. Our
      biochemistry and molecular analysis indicated that a PEST domain in the N
      terminal could be important for STI functioning in regulating trichome branching.
      It can directly interact with BRACHLESS TRICHOME (BLT), an important linker of
      cell shape and endoreplication. Because the previously data showed that the
      function of STI in regulating trichome branching was not linked to DNA
      replication and actin or microtubule cytoskeleton configuration, our findings of
      the direct interaction domains between STI and BLT veiled the probable roles of
      STI in cell morphogenesis.

PMID- 29601815
TI  - Discovery and characterization of selective small molecule inhibitors of the
      mammalian mitochondrial division dynamin, DRP1.
AB  - Balanced rates of mitochondrial division and fusion are required to maintain
      mitochondrial function, as well as cellular and organismal homeostasis. In
      mammals, the cellular machines that mediate these processes are dynamin-related
      GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2
      and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are
      linked to varied pathologies, including cell death and neurodegeneration, raising
      the possibility that small molecules that target the division and fusion machines
      to restore balance may have therapeutic potential. Here we describe the discovery
      of novel small molecules that directly and selectively inhibit assembly
      stimulated GTPase activity of the division dynamin, DRP1. In addition, these
      small molecules restore wild type mtDNA copy number in MFN1 knockout mouse
      embryonic fibroblast cells, a phenotype linked to deficient mitochondrial fusion
      activity. Thus, these compounds are unique tools to explore the roles of
      mitochondrial division in cells, and to assess the potential therapeutic efficacy
      of rebalancing mitochondrial dynamics in pathologies associated with excessive
      mitochondrial division.

PMID- 29601816
TI  - Biophysical study of human induced Pluripotent Stem Cell-Derived cardiomyocyte
      structural maturation during long-term culture.
AB  - Human induced Pluripotent Stem Cell-derived cardiomyocytes (hiPSC-CMs) have an
      enormous potential for the development of drug screening and modeling cardiac
      disease platforms. However, early hiPSC-CMs usually exhibit low structural
      development, precluding the applicability of these cells. Here, we follow during
      120 days the progressive structural maturation of hiPSC-CM microtissues obtained
      using the Wnt signaling modulation protocol. For this purpose, we designed a user
      friendly custom-written program to quantify cardiac fiber alignment and sarcomere
      length. Cardiomyocyte shape, cardiac fiber density and multinucleation were also
      analyzed. Derived cardiomyocytes showed significant progression in cardiomyocyte
      fiber density and sarcomere length during the long-term culture, with a peak at
      day 90 of 40% multinucleated cells. In addition, cardiomyocyte microtissues
      remained functional with progressive maturation leading to a decrease in the
      percentage of cTnT positive cells from 59% to 22% at day 120, a value similar to
      the content present in tissues of the adult left ventricle. These data and the
      framework that we provide to quantify cardiomyocyte structural features can be
      important to set new metrics to develop applications for drug screening and
      disease modeling.

PMID- 29601818
TI  - Hepatic NPC1L1 promotes hyperlipidemia in LDL receptor deficient mice.
AB  - BACKGROUND AND AIMS: Niemann-Pick C1-like1 (NPC1L1), a crucial cholesterol
      absorption receptor expressed in human intestine and liver. But in mouse it is
      only expressed in intestine. Previous studies elucidated that expression of human
      NPC1L1 in mouse liver led to increase of plasma cholesterol due to activation of
      absorption from bile. However, hepatic NPC1L1 function was not elucidated in LDL
      receptor deficient mouse (LDLR-/-) in which LDL was a main lipoprotein as in
      human. METHODS AND RESULTS: L1-Tg/LDLR-/- mouse was created by crossing liver
      specific NPC1L1 transgenic mouse (L1-Tg) with LDLR-/-. L1-Tg/LDLR-/- mice
      developed hyperlipidemia when fed with atherogenic diet (AD) containing 0.2%
      cholesterol for 21days. Compared with control mice, biliary cholesterol level in
      L1-Tg/LDLR-/- mice was significantly lower, plasma cholesterol level was
      significantly higher in L1-Tg/LDLR-/- mice under both chow diet and AD feeding.
      New finding in this study is augmentations of plasma TAG L1-Tg/LDLR-/- mice fed
      with AD. Results were shown that very low density lipoprotein (VLDL) secretion
      was elevated in L1-Tg/LDLR-/- mice after AD fed. The increase of VLDL secretion
      was further confirmed by higher expression of hepatic triacylglycerol hydrolase
      (TGH) and microsomal triglyceride transfer protein (MTP). CONCLUSION: L1-Tg/LDLR
      /- mouse is a humanized model to study cholesterol absorption and transportation.
      The results obtained from L1-Tg/LDLR-/- mouse indicated no feedback mechanism to
      inhibit NPC1L1 function in liver and hepatic expression of NPC1L1 correlated with
      VLDL secretion in hypercholesterolemia state.

PMID- 29601817
TI  - GLP-1 receptor agonist liraglutide exerts central action to induce beta-cell
      proliferation through medulla to vagal pathway in mice.
AB  - Endogenous GLP-1 and GLP-1 receptor agonists (GLP-1RAs) regulate glucose
      metabolism via common and distinct mechanisms. Postprandial release of GLP-1 is
      modest and it is degraded by DPP-4 within 2 min, and hence it cannot enter the
      brain in substantial amount. In contrast, DPP-4-resistant GLP-1RAs are
      administered at 10 times higher concentration than endogenous GLP-1 level, which
      enables them to reach several brain regions including ARC and AP, the areas
      implicated in glucose metabolism. Hence, some of the effects of GLP-1RAs observed
      clinically and experimentally, including pancreatic beta-cell proliferation, are
      thought to involve the brain. However, the effects of centrally acting GLP-1/GLP
      1RAs on glucose metabolism and underlying neural mechanism are unclear. This
      study aimed to establish the link of central GLP-1/GLP-1RA action to pancreatic
      beta-cell proliferation. Both subcutaneous (SC) and intracerebroventricular (ICV)
      injections of liraglutide increased the number of pancreatic beta-cells
      expressing Ki67 and PCNA, proliferation markers, in C57BL/6J mice. This effect
      was induced by single ICV administration of liraglutide at relatively low dose
      that was incapable of suppressing food intake. These SC and ICV liraglutide
      induced effects were inhibited by 50% and 70%, respectively, by pretreatment with
      atropine, a muscarinic receptor blocker. ICV liraglutide induced c-Fos expression
      in the area postrema (AP), nucleus tractus solitaries (NTS), and dorsal motor
      nucleus of the vagus (DMX) of the brain stem. These results demonstrate that
      central action of liraglutide induces pancreatic beta-cell proliferation via the
      pathway involving the brain stem AP/NTS/DMX area and vagus nerve. This route is
      highly sensitive to GLP-1/GLP-1RA. Hence, this brain-pancreatic beta-cell pathway
      may operate in type 2 diabetic patients treated with GLP-RAs and serve to
      counteract the reduction of beta-cell mass.

PMID- 29601819
TI  - The crystal structure and oligomeric form of Escherichia colil,d-carboxypeptidase
      A.
AB  - Bacterial peptidoglycan is constructed by cross-linking sugar chains carrying
      pentapeptide building blocks with two d-alanine residues at the C-terminus.
      Incorporation into the polymer and subsequent breakdown of peptidoglycan releases
      a tetrapeptide with a single d-alanine residue. Removal of this residue is
      necessary for the tripeptide to receive a new D-Ala-D-Ala dipeptide in the
      synthetic pathway, but proteases are generally unable to work with substrates
      having residues of unusual chirality close to the scissile bond. Processing of
      the tetrapeptide is carried out by a dedicated ld-carboxypeptidase, which is of
      interest as a novel drug target. We describe the high resolution crystal
      structure of the enzyme from E. coli, and demonstrate the dimeric structure is
      highly conserved.

PMID- 29601820
TI  - Dense B-Scan Optical Coherence Tomography Angiography.
AB  - PURPOSE: To describe a novel imaging technique, which we call "dense B-scan
      optical coherence tomography angiography" (DB OCTA), in which thin dense raster
      scans are used to produce highly resolved structural B-scans with superimposed
      flow signal that provide precise correlation between retinal microstructure and
      blood flow. DESIGN: Observational case series. METHODS: Normal eyes and eyes with
      macular findings of interest were imaged with DB OCTA in which 150-400 OCT B
      scans were acquired within a narrow area (from a single line to 1 degree) with a
      width of 10-30 degrees. B-scans containing 5-7 consecutive frames were processed
      for OCTA signal and then combined and visualized post-acquisition by application
      of a Gaussian filter across neighboring scans. The result was a single, smoothed,
      high-resolution image that contained both structural and flow information.
      Tracked follow-up DB OCTA was used to detect subtle changes in pathology over
      time. RESULTS: Two hundred and thirty-seven eyes from 205 subjects aged 18-100
      years (mean 72.88 +/- 14.74 years) with a diverse range of macular findings were
      imaged with DB OCTA. Highly resolved scans showing precise localization of flow
      signal were readily obtained, even in patients with poor visual acuity and/or
      poor fixation. We present clinical examples that demonstrate the utility of DB
      OCTA for visualizing the associations between retinal microstructure and blood
      flow. CONCLUSIONS: DB OCTA enables precise correlation between retinal
      microstructure and blood flow. The ability to obtain accurately aligned follow-up
      DB OCTA studies has the potential to refine the understanding and clinical
      management of a wide range of macular diseases.

PMID- 29601821
TI  - Chronic Anterior Uveitis in Children: Psychosocial Challenges for Patients and
      Their Families.
AB  - PURPOSE: To describe issues of concern to children with chronic anterior uveitis;
      to consider the psychological impact of chronic anterior uveitis on children's
      lives; and to understand the effect of a child's chronic illness on other family
      members. DESIGN: Expert commentary. METHODS: Author experiences were supplemented
      by a review of pertinent medical literature and by consideration of content from
      semi-structured, separate patient and parent interviews. RESULTS: Vision loss and
      the fear of blindness are not the only stressors for children with chronic
      anterior uveitis and their families; of additional concern are the burdens of
      examinations and treatment regimens, as well as drug toxicities. Children with
      chronic anterior uveitis experience medical, academic, interpersonal,
      psychological, and developmental challenges. The impact of disease extends to
      other members of a patient's family as well; parents experience challenges in
      similar domains. Problems with adherence to medical regimens are common. Both the
      disease and its treatment affect quality of life, and can interfere with
      successful management of disease and transition to autonomy in adulthood, as
      reported for other chronic conditions. Coping processes vary greatly between
      different families. CONCLUSIONS: Eye examinations and the rigors of long-term
      treatment often influence the psychosocial health of patients and families;
      physicians who are aware of these issues can help patients and families cope with
      chronic illness and may improve outcomes. Further psychosocial research to
      understand the experiences of children dealing with chronic anterior uveitis is
      warranted; this commentary can serve as a foundation for development of age- and
      disease-specific research questions.

PMID- 29601822
TI  - Pars Plana Vitrectomy for the Treatment of Uveitis.
AB  - PURPOSE: To review and summarize evidence in the medical literature regarding the
      use of pars plana vitrectomy in the management of uveitis. DESIGN: Systematic
      literature review. METHODS: A systematic literature search was conducted for
      relevant articles on pars plana vitrectomy for the management of uveitis. Results
      from the studies were compiled and analyzed. RESULTS: Thirty-four articles,
      published from 2005 through 2014, were included in the final data analysis.
      Thirty-two manuscripts were from retrospective case series and 2 manuscripts were
      from randomized pilot studies. The median Scottish Intercollegiate Guidelines
      Network level of evidence grade was 3 and the median Oxford Center for Evidence
      based Medicine level of evidence grade was 4. Fewer than 50% of the articles in
      the current study applied Standardization of Uveitis Nomenclature (SUN) criteria
      in regard to reporting the anatomic location of uveitis, fewer than 25% of
      studies applied SUN criteria in regard to the reporting of anterior chamber cells
      before and after PPV, fewer than 10% of studies applied SUN criteria to the
      grading of anterior chamber flare before and after PPV, and fewer than 10% of
      studies applied standardized criteria to the grading of vitreous haze after PPV.
      Overall, 627 patients and 708 total eyes undergoing PPV for uveitis were
      included. The average reported age of all patients was 43.4 years. The median
      duration of uveitis prior to PPV reported in the studies was 36.1 months (range 4
      198 months). The median follow-up after PPV reported in the studies was 18.9
      months (range 2-114 months). Vision was reported for 519 eyes and was improved in
      356 eyes (69%), unchanged in 95 eyes (18%), and worse in 68 eyes (13%) following
      PPV. Preoperatively, 157 of 300 (52%) eyes in these studies had documented
      cystoid macular edema compared to 112 of 300 (37%) postoperatively. Median use of
      oral corticosteroids improved from 48% preoperatively to 12% postoperatively
      among the reporting studies. Median use of other immunosuppressive medications
      decreased from 56% preoperatively to 36% postoperatively among the reporting
      studies. CONCLUSIONS: Although nearly all studies continue to report favorable
      outcomes of PPV in the management of uveitis, the quality of data remains limited
      by a lack of application of standardized reporting outcomes, limitations in study
      design, and a paucity of prospective data.

PMID- 29601823
TI  - Cholesterol modulates the binding properties of human relaxin family peptide
      receptor 3 with its ligands.
AB  - Relaxin family peptide receptor 3 (RXFP3) is implicated in the regulation of food
      intake and stress response upon activation by its cognate agonist relaxin-3. As
      an A-class G protein-coupled receptor, RXFP3 is an integral plasma membrane
      protein with seven transmembrane domains, yet influence of the membrane lipids on
      its function remains unknown. In the present study, we disclosed that
      cholesterol, an essential membrane lipid for mammalian cells, modulated the
      binding properties of human RXFP3 with its ligands. We first demonstrated that
      depletion of cholesterol from host human embryonic kidney (HEK) 293T cells by
      methyl-beta-cyclodextrin altered ligand-binding properties of the overexpressed
      human RXFP3, such as increasing its binding potency with some antagonists and
      decreasing its binding affinity with a NanoLuc-conjugated R3/I5 tracer.
      Thereafter, we demonstrated that two B-chain residues, B5Tyr and B12Arg, were
      primarily responsible for the increased binding potency of these antagonists with
      human RXFP3 under the cholesterol depletion condition. Our results suggest that
      cell membrane cholesterol interacts with human RXFP3 and modulates its ligand
      binding properties, providing new insights into the influence of membrane lipids
      on RXFP3 function.

PMID- 29601824
TI  - Optical assessment of skin carotenoid status as a biomarker of vegetable and
      fruit intake.
AB  - Resonance Raman spectroscopy (RRS) and reflection spectroscopy (RS) are optical
      methods applicable to the non-invasive detection of carotenoids in human skin.
      RRS is the older, more thoroughly validated method, whereas RS is newer and has
      several advantages. Since collective skin carotenoid levels serve as a biomarker
      for vegetable and fruit intake, both methods hold promise as convenient screening
      tools for assessment of dietary interventions and correlations between skin
      carotenoids and health and disease outcomes. In this manuscript, we describe the
      most recent optimized device configurations and compare their use in various
      clinical and field settings. Both RRS and RS devices yield a wide range of skin
      carotenoid levels between subjects, which is a critical feature for a biomarker.
      Repeatability of the methods is 3-15% depending on the subject's skin carotenoid
      level and the uniformity of its local distribution. For 54 subjects recruited
      from an ophthalmology clinic, we first checked the validity of the relatively
      novel RS methodology via biochemical serum carotenoid measurements, the latter
      carried out with high performance liquid chromatography (HPLC). A high
      correlation between RS skin and serum HPLC carotenoid levels was established (R =
      0.81; p < 0.001). Also, a high correlation was found between RS and RRS skin
      levels (R = 0.94 p < 0.001). Subsequent comparisons of skin carotenoid
      measurements in diverse age groups and ethnicities included 569 Japanese adults,
      947 children with ages 2-5 screened in 24 day care centers in San Francisco, and
      49 predominantly Hispanic adults screened at an outdoor health fair event.
      Depending on the particular subject group, correlation coefficients between the
      RRS and RS methods ranged between R ~0.80 and R ~0.96. Analysis of the Japanese
      screening showed that, on average, skin carotenoid levels are higher in women
      compared to men, skin levels do not depend on age, and tobacco smokers have
      reduced levels versus non-smokers. For the two most ethnically diverse groups
      with widely varying melanin levels, we investigated the effect of dermal melanin
      on RS and RRS skin carotenoid levels. The analysis revealed that large variations
      in skin carotenoid levels remain detectable independent of the particular melanin
      index. This behavior is consistent with the absence of melanin effects on the
      skin carotenoid levels generated with the instrument configurations. The RS
      method has an advantage over RRS in its relative simplicity. Due to its detection
      of skin reflection over a wide spectral range from the near UV to the near IR, it
      has the unique ability to quantify each of the major tissue chromophores and take
      them into account in the derivation of skin carotenoid levels.

PMID- 29601826
TI  - Why Won't the Alpha-fetoprotein Test Go Gentle Into the Good Night?

PMID- 29601825
TI  - Identification of Endpoints for Development of Antifibrosis Drugs for Treatment
      of Crohn's Disease.
AB  - BACKGROUND & AIMS: Intestinal fibrosis is a challenge to management of patients
      with Crohn's disease (CD); there is an urgent need to expedite development of
      antifibrosis drugs for this disease. The International Organization for the Study
      of Inflammatory Bowel Disease (IOIBD) aimed to identify a set of endpoints that
      can be used to determine efficacy of antifibrosis agents tested in clinical
      trials of patients with CD. METHODS: We conducted a systematic review to identify
      clinical, radiologic, biochemical, endoscopic, and composite endpoints used in
      assessing activity of fibrostenosing CD and response to treatment, and determined
      their operational properties. A panel of IOIBD experts performed a consensus
      process to identify the best endpoints for inclusion in clinical trials, through
      a 2-round, Delphi-style online survey. RESULTS: A total of 36 potentially
      relevant endpoints for intestinal fibrosis were selected and assessed. Forty
      eight physicians with expertise in inflammatory bowel disease, from 5 regions
      (North America, Europe, Middle East, Asia/Pacific, and Latin America),
      participated in the Delphi consensus process. A core set of 13 endpoints
      (complete clinical response, long-term efficacy, sustained clinical benefit,
      treatment failure, radiological remission, normal quality of life, clinical
      remission without steroids, therapeutic failure, deep remission, complete absence
      of occlusive symptoms, symptom-free survival, bowel damage progression, and no
      disability) were rated as critical. Agreement was high among the experts.
      CONCLUSIONS: Members of the IOIBD reached expert consensus on a set of endpoints
      that can be used to assess antifibrosis agents in trials of patients with CD.
      Studies are needed to clarify methods for measuring these outcomes and validate
      measurement instruments.

PMID- 29601827
TI  - Should the Presence of Spontaneous Portosystemic Shunts Be Implemented to the
      Model for End-Stage Liver Disease Score for a Better Prediction of Outcome?

PMID- 29601828
TI  - Identification of Variants in RET and IHH Pathway Members in a Large Family With
      History of Hirschsprung Disease.
AB  - BACKGROUND & AIMS: Hirschsprung disease (HSCR) is an inherited congenital
      disorder characterized by absence of enteric ganglia in the distal part of the
      gut. Variants in ret proto-oncogene (RET) have been associated with up to 50% of
      familial and 35% of sporadic cases. We searched for variants that affect disease
      risk in a large, multigenerational family with history of HSCR in a linkage
      region previously associated with the disease (4q31.3-q32.3) and exome wide.
      METHODS: We performed exome sequencing analyses of a family in the Netherlands
      with 5 members diagnosed with HSCR and 2 members diagnosed with functional
      constipation. We initially focused on variants in genes located in 4q31.3-q32.3;
      however, we also performed an exome-wide analysis in which known HSCR or HSCR
      associated gene variants predicted to be deleterious were prioritized for further
      analysis. Candidate genes were expressed in HEK293, COS-7, and Neuro-2a cells and
      analyzed by luciferase and immunoblot assays. Morpholinos were designed to target
      exons of candidate genes and injected into 1-cell stage zebrafish embryos.
      Embryos were allowed to develop and stained for enteric neurons. RESULTS: Within
      the linkage region, we identified 1 putative splice variant in the
      lipopolysaccharide responsive beige-like anchor protein gene (LRBA). Functional
      assays could not confirm its predicted effect on messenger RNA splicing or on
      expression of the mab-21 like 2 gene (MAB21L2), which is embedded in LRBA.
      Zebrafish that developed following injection of the lrba morpholino had a
      shortened body axis and subtle gut morphological defects, but no significant
      reduction in number of enteric neurons compared with controls. Outside the
      linkage region, members of 1 branch of the family carried a previously
      unidentified RET variant or an in-frame deletion in the glial cell line derived
      neurotrophic factor gene (GDNF), which encodes a ligand of RET. This deletion was
      located 6 base pairs before the last codon. We also found variants in the Indian
      hedgehog gene (IHH) and its mediator, the transcription factor GLI family zinc
      finger 3 (GLI3). When expressed in cells, the RET-P399L variant disrupted protein
      glycosylation and had altered phosphorylation following activation by GDNF. The
      deletion in GDNF prevented secretion of its gene product, reducing RET
      activation, and the IHH-Q51K variant reduced expression of the transcription
      factor GLI1. Injection of morpholinos that target ihh reduced the number of
      enteric neurons to 13% +/- 1.4% of control zebrafish. CONCLUSIONS: In a study of
      a large family with history of HSCR, we identified variants in LRBA, RET, the
      gene encoding the RET ligand (GDNF), IHH, and a gene encoding a mediator of IHH
      signaling (GLI3). These variants altered functions of the gene products when
      expressed in cells and knockout of ihh reduced the number of enteric neurons in
      the zebrafish gut.

PMID- 29601830
TI  - Clostridium difficile Infection and the Tangled Web of Interactions Among Host,
      Pathogen, and Microbiota.

PMID- 29601829
TI  - Thirty-Day Readmission Among Patients With Non-Variceal Upper Gastrointestinal
      Hemorrhage and Effects on Outcomes.
AB  - BACKGROUND & AIMS: We aimed to determine the rate of hospital readmission within
      30 days of non-variceal upper gastrointestinal hemorrhage and its impact on
      mortality, morbidity, and health care use in the United States. METHODS: We
      performed a retrospective study using the Agency for Healthcare Research and
      Quality's Healthcare Cost and Utilization Project Nationwide Readmission Database
      for the year 2014 (data on 14.9 million hospital stays at 2048 hospitals in 22
      states). We collected data on hospital readmissions of 203,220 adults who were
      hospitalized for urgent non-variceal upper gastrointestinal hemorrhage and
      discharged. The primary outcome was rate of all-cause readmission within 30 days
      of discharge. Secondary outcomes were reasons for readmission, readmission
      mortality rate, morbidity (shock and prolonged mechanical ventilation) and
      resource use (length of stay and total hospitalization costs and charges).
      Independent risk factors for readmission were identified using Cox regression
      analysis. RESULTS: The 30-day rate of readmission was 13%. Only 18% of
      readmissions were due to recurrent non-variceal upper gastrointestinal bleeding.
      The rate of death among patients readmitted to the hospital (4.7%) was higher
      than that for index admissions (1.9%) (P < .01). A higher proportion of
      readmitted patients had morbidities requiring prolonged mechanical ventilation
      (1.5%) compared with index admissions (0.8%) (P < .01). A total of 133,368
      hospital days was associated with readmission, and the total health care in
      hospital economic burden was $30.3 million (in costs) and $108 million (in
      charges). Independent predictors of readmission were Medicaid insurance, higher
      Charlson comorbidity score, lower income, residence in a metropolitan area,
      hemorrhagic shock, and longer stays in the hospital. Older age, private or no
      insurance, upper endoscopy, and prolonged mechanical ventilation were associated
      with lower odds for readmission. CONCLUSIONS: In a retrospective study of
      patients hospitalized for non-variceal upper gastrointestinal hemorrhage, 13% are
      readmitted to the hospital within 30 days of discharge. Readmission is associated
      with higher mortality, morbidity, and resource use. Most readmissions are not for
      recurrent gastrointestinal bleeding.

PMID- 29601831
TI  - Enhanced amphetamine-induced motor impulsivity and mild attentional impairment in
      the leptin-deficient rat model of obesity.
AB  - Evidence suggests that impulse control deficits contribute to excessive food
      intake in some individuals with obesity. In addition to its known role in
      regulating appetite and glucose metabolism, the hormone leptin also directly
      modulates the activity of central dopamine systems. Although dopamine is involved
      in regulating impulsivity, the influence of leptin per se on this cognitive
      domain remains unclear. This study explored the performance of male leptin
      knockout (KO) and wild type (WT) rats in the 5-Choice Serial Reaction Time task
      (5CSRTT) of motor impulsivity and visuospatial attention. Behavioural performance
      was assessed under baseline conditions, following 4 weeks high-fat diet (HFD; 60
      kcal%) consumption, and after acute pharmacological challenge with the indirect
      dopamine agonist, amphetamine. Subjects were also tested for glucose tolerance
      and insulin sensitivity, and dorsal and ventral striatal tissue was assayed ex
      vivo for markers of dopaminergic transmission. Obese KO rats learned the 5CSRTT
      at a slower rate compared to WT rats, in a manner suggestive of mild attentional
      impairment. However, task performance at baseline and after HFD intake was
      similar to that of WT controls. HFD intake reduced omissions across all subjects,
      whereas amphetamine challenge revealed a prominent genotype effect on 5CSRTT
      performance, with potentiated levels of impulsive responding and faster response
      times in KO rats compared to WT animals. Effects of amphetamine on other
      variables were similar between genotypes. Notably, the expression of striatal
      dopaminergic markers was unchanged in KO rats, and neither chronic food
      restriction nor HFD intake altered the impairments in glucose or insulin
      metabolism previously reported in these animals. These data suggest that leptin
      deficiency enhances impulsive action under conditions of dopaminergic challenge,
      yet this seems independent of overt changes in the expression of post-synaptic
      markers of dopamine signalling in striatal regions.

PMID- 29601832
TI  - Antidepressant effects of acupoint stimulation and fluoxetine by increasing
      dendritic arborization and spine density in CA1 hippocampal neurons of socially
      isolated rats.
AB  - Given the importance of depression and the adverse effects of conventional
      treatment, it is necessary to seek complementary therapies. In a rat model of
      depression, this study aimed to assess the behavioral and morphological effects
      of embedding absorbable thread in acupoints (acu-catgut), and compare the results
      to those of fluoxetine treatment and the corresponding control groups. Therefore,
      depressive-like behavior was evaluated with the forced swimming test, and
      dendritic morphology (in the CA1 hippocampal region) with the Golgi-Cox technique
      and Sholl analysis. After weaning, male Sprague-Dawley rats were housed in social
      isolation for 8 weeks to induce depressive-like behavior. They were then given a
      21-day treatment by stimulating acupoints with acu-catgut (AC) or fluoxetine (FX)
      (2 mg/kg). Rats were divided into six groups: Control (socially housed), social
      isolation (SI), SI + AC, SI + Sham (sham embedding of thread), SI + FX and SI +
      VH (vehicle). Compared to fluoxetine, acu-catgut treatment was more effective in
      reversing depressive-like behavior elicited by SI. The SI-induced reduction in
      dendritic length and spine density in hippocampal CA1 pyramidal neurons was
      attenuated after prolonged treatment with acu-catgut or fluoxetine. Hence, both
      treatments proved capable of reversing depressive-like alterations caused by SI,
      likely due to dendritic remodeling in the hippocampus.

PMID- 29601834
TI  - Node balanced steady states: Unifying and generalizing complex and detailed
      balanced steady states.
AB  - We introduce a unifying and generalizing framework for complex and detailed
      balanced steady states in chemical reaction network theory. To this end, we
      generalize the graph commonly used to represent a reaction network. Specifically,
      we introduce a graph, called a reaction graph, that has one edge for each
      reaction but potentially multiple nodes for each complex. A special class of
      steady states, called node balanced steady states, is naturally associated with
      such a reaction graph. We show that complex and detailed balanced steady states
      are special cases of node balanced steady states by choosing appropriate reaction
      graphs. Further, we show that node balanced steady states have properties
      analogous to complex balanced steady states, such as uniqueness and asymptotic
      stability in each stoichiometric compatibility class. Moreover, we associate an
      integer, called the deficiency, to a reaction graph that gives the number of
      independent relations in the reaction rate constants that need to be satisfied
      for a positive node balanced steady state to exist. The set of reaction graphs
      (modulo isomorphism) is equipped with a partial order that has the complex
      balanced reaction graph as minimal element. We relate this order to the
      deficiency and to the set of reaction rate constants for which a positive node
      balanced steady state exists.

PMID- 29601833
TI  - Modelling leptospirosis in livestock.
AB  - New Zealand has one of the highest (per capita) incidences of human leptospirosis
      in the world. It is the highest occurring occupational disease in New Zealand,
      often transmitted from livestock such as deer, sheep and cattle to humans. A
      cyclical model, showing the dynamics of infection of leptospirosis in farmed
      livestock in New Zealand, is presented. The limit cycle, bifurcation diagram and
      quasi-R0 value of the system are determined. Leptospire death rate is used as a
      control parameter. Previously published parameter values are used in a case study
      to produce figures demonstrating analytical results. The model is used to predict
      conditions under which the infection will persist in the population.

PMID- 29601835
TI  - Photoacoustic imaging of synovial tissue hypoxia in experimental post-traumatic
      osteoarthritis.
AB  - OBJECTIVES: This pilot study aimed to investigate the feasibility of non
      invasively assessing synovial tissue hypoxia in vivo using photoacoustic (PA)
      imaging in a post-traumatic osteoarthritis model and explore its correlation with
      OA severity. METHODS: The three-dimensional vasculature structure and oxygenation
      level of synovial tissues of destabilization of the medial meniscus (DMM)-induced
      osteoarthritis (OA) mice were longitudinally monitored using PA imaging. Vascular
      volume/tissue volume (%) and tissue oxygen saturation (sO2) were validated
      against results obtained by established Power Doppler (PD) imaging and dynamic
      changes of inhaled O2 concentration respectively. PA changes were correlated with
      the histological grading of cartilage damages. RESULTS: PA-measurements of
      vascularity and sO2 demonstrated a strong correlation with localized blood flow
      detected by PD imaging (r = 0.506, p < 0.001) and inhaled O2 concentration. DMM
      knees exhibited much more vascularity in synovial tissue at 4 months after
      surgery (median 11.3%, IQR: 10.7-15.5%) than the intact knees at time zero
      (median:5.1%, IQR:3.8-6.8%, p < 0.001) as well as the sham-operated knees
      (median: 4%, IQR: 3.75-5.45%, p = 0.017). Paradoxically, synovial tissue sO2 was
      significantly lower in DDM knees (median: 37.7%, IQR: 36.4-40.6%) than both the
      intact (47.1%, IQR: 41.9-49.8% p = 0.001) and sham-operated knees (45.1% IQR:
      45.1-52.4%, p = 0.017). The PA-detected synovial tissue hypoxia correlated with
      the severity of cartilage loss in DMM mice (rho = -0.597, p = 0.031). CONCLUSION:
      Here, we demonstrated PA imaging can be implemented for non-invasive imaging of
      the synovial tissue. Under PA imaging, synovitis in OA was characterized by
      increased angiogenesis and synovial tissue hypoxia; the latter was associated
      with the severity of OA.

PMID- 29601836
TI  - Unplanned Emergency Department Visits and Hospital Admissions Following
      Ureteroscopy: Do Ureteral Stents Make a Difference?
AB  - OBJECTIVE: To evaluate unplanned medical visits within the early postoperative
      period after ureteroscopy in patients with and without ureteral stent placement.
      MATERIALS AND METHODS: We identified all ureteroscopic procedures for urinary
      stone disease in the California Office of Statewide Health Planning and
      Development database from 2010 to 2012. The primary outcome was any emergency
      department visit or inpatient hospital admission in the first 7 days following
      ureteroscopy. Patients were subcategorized by type of ureteroscopy (ie, laser
      lithotripsy vs basket retrieval) and were analyzed for significant differences
      between stented and unstented patients. Multivariable logistic regression was
      performed to determine if ureteral stent placement was independently associated
      with unplanned visits. RESULTS: Our analytic cohort included 16,060 patients
      undergoing 17,716 ureteroscopy procedures. A ureteral stent was placed in 86.2%
      of patients undergoing laser lithotripsy and in 70.5% of patients receiving
      basket retrieval. In the 7 days following ureteroscopy, 6.6% of patients were
      seen in the emergency department and 2.2% of patients were admitted to a
      hospital. In a fully adjusted model, the utilization of a ureteral stent was not
      associated with emergency department visits or inpatient admissions. CONCLUSION:
      Ureteral stent placement during ureteroscopy is not associated with an increased
      odds of emergency department visits and inpatient admissions in the early
      postoperative period.

PMID- 29601837
TI  - Re: Huang et al.: The Application of Suctioning Flexible Ureteroscopy with
      Intelligent Pressure Control in Treating Upper Urinary Tract Calculi on Patients
      with a Solitary Kidney (Urology 2018;111:44-47).

PMID- 29601838
TI  - Successful Conservative Management of Bilateral Renal Mucormycosis.

PMID- 29601839
TI  - Japan-Specific Key Regulatory Aspects for Development of New Biopharmaceutical
      Drug Products.
AB  - Japan represents the third largest pharmaceutical market in the world. Developing
      a new biopharmaceutical drug product for the Japanese market is a top business
      priority for global pharmaceutical companies while aligning with ethical drivers
      to treat more patients in need. Understanding Japan-specific key regulatory
      requirements is essential to achieve successful approvals. Understanding the full
      context of Japan-specific regulatory requirements/expectations is challenging to
      global pharmaceutical companies due to differences in language and culture. This
      article summarizes key Japan-specific regulatory
      aspects/requirements/expectations applicable to new drug development, approval,
      and postapproval phases. Formulation excipients should meet Japan compendial
      requirements with respect to the type of excipient, excipient grade, and
      excipient concentration. Preclinical safety assessments needed to support
      clinical phases I, II, and III development are summarized. Japanese regulatory
      authorities have taken appropriate steps to consider foreign clinical data,
      thereby enabling accelerated drug development and approval in Japan. Other
      important topics summarized in this article include: Japan new drug application
      specific bracketing strategies for critical and noncritical aspects of the
      manufacturing process, regulatory requirements related to stability studies,
      release specifications and testing methods, standard processes involved in pre
      and postapproval inspections, management of postapproval changes, and Japan
      regulatory authority's consultation services available to global pharmaceutical
      companies.

PMID- 29601840
TI  - Protein Nanoparticles Promote Microparticle Formation in Intravenous
      Immunoglobulin Solutions During Freeze-Thawing and Agitation Stresses.
AB  - In this study, we investigated the potential roles of nanoparticles (<100 nm) and
      submicron (100-1000 nm) particles in the formation of microparticles (>1000 nm)
      in protein formulations under some pharmaceutically relevant stress conditions.
      Exposure of intravenous immunoglobulin solutions to the interface-associated
      stresses of freeze-thawing or agitation resulted in relatively large increases in
      microparticle concentrations, which depended directly on the levels of pre
      existing nano- and submicron particles. Thus, agglomeration of nanoparticles and
      submicron particles appears to play a role in microparticle formation under these
      stresses. In contrast, increases in microparticle concentrations during quiescent
      incubation at elevated temperatures were independent of the initial nano- and
      submicron particle concentrations in solution.

PMID- 29601841
TI  - Intratumoral and peritumoral lymphovascular invasion detected by D2-40
      immunohistochemistry correlates with metastasis in primary cutaneous Merkel cell
      carcinoma.
AB  - Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine
      malignancy in which lymphovascular invasion (LVI) correlates with more aggressive
      phenotype. The prognostic significance of LVI detected by D2-40
      immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine
      how LVI detected by D2-40 IHC compares with LVI detected by hematoxylin and eosin
      (H&E) staining in predicting MCC metastasis. Clinical and histopathologic
      features of MCCs diagnosed and treated in 2002 to 2015 were assembled and
      included 58 MCC tumors from 58 patients. H&E-stained tissue sections and D2-40
      IHC studies were reviewed. When LVI was present, the location (peritumoral or
      intratumoral) and the size of the largest invaded vessel were recorded. LVI
      findings by H&E staining and D2-40 IHC were compared with each other and with
      histologic features and clinical outcomes. H&E staining showed LVI in 37 of 58
      cases; D2-40 IHC confirmed LVI in 30 of these cases but failed to confirm LVI in
      7. D2-40 IHC also detected 14 cases of LVI not identified on H&E staining.
      Histologically, D2-40-detected LVI was associated with infiltrative growth
      pattern and nonbrisk lymphoid infiltrate (P = .005 and P = .055, respectively).
      There was a statistically significant difference between the frequency of
      detection of peritumoral LVI by H&E in comparison to D2-40 IHC (P = .0009). MCCs
      in which D2-40 IHC-detected both intratumoral and peritumoral LVI were typically
      larger than MCCs without (mean, 24.5 mm versus 17.3 mm; P = .03) and more
      frequently metastasized (87% versus 51%; P = .03). D2-40 IHC detection of both
      intratumoral and peritumoral LVI is associated with metastasis.

PMID- 29601842
TI  - Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in
      micropapillary urothelial carcinoma.
AB  - Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of
      urothelial carcinoma. MPUC has been shown to commonly exhibit ERBB2 amplification
      and HER2 protein overexpression, but the frequency and distribution of these
      findings within micropapillary (MP) and not otherwise specified (NOS) components
      of tumors with mixed histology have not been addressed. Therefore, we evaluated
      ERBB2 amplification and HER2 expression in 43 MPUC cases by fluorescence in situ
      hybridization (FISH) and immunohistochemistry (IHC). Of the 35 tumors containing
      both MP and NOS components, ERBB2 amplification was present in both the MP and
      NOS components of 12 tumors (34.3%), in only the MP component of 11 tumors
      (31.4%), and exclusively in the NOS component of 4 tumors (11.4%). HER2 protein
      overexpression was significantly more commonly present in the MP component
      compared to the NOS component within the same tumor (68.6% versus 34.3%, P =
      .012). Overall, there was a moderately positive correlation between HER2 protein
      expression and ERBB2 amplification in both MP (rho = 0.59, P < .001) and NOS (rho
      = 0.70, P < .001) components. All MP/NOS areas with IHC score 3+ and none of
      MP/NOS areas with IHC score 0 were associated with ERBB2 amplification. We
      conclude that ERBB2 amplification and HER2 overexpression are preferentially but
      not exclusively identified in the MP component compared to the NOS component
      within the same tumor. Our findings identify the presence of intratumoral
      heterogeneity of ERBB2 amplification and HER2 expression in MPUC and provide
      grounds for further investigation into the mechanisms underlying the development
      of MPUC.

PMID- 29601843
TI  - Development and validation of rt-qpcr for vesicular stomatitis virus detection
      (Alagoas vesiculovirus).
AB  - Vesicular stomatitis is an infectious disease that occurs mainly in countries of
      the Western Hemisphere and affects cattle, swine and horses. The clinical
      symptoms in cattle and swine are similar to foot-and-mouth disease and include
      vesicular ulceration of the tongue and mouth. The disease requires a rapid and
      accurate differential diagnosis, aiming for immediate implementation of control
      measures. The objective of the present study was to develop and perform
      validation tests of multiplex RT-qPCR(s) for the detection of RNA from Alagoas
      vesiculovirus, considering the parameters of sensitivity and analytical
      specificity, analytical performance (repeatability and reproducibility criteria)
      and the uncertainty of the measurement. The threshold cycle values obtained in
      triplicate from each sample were evaluated by considering the variations between
      days, analysts and equipment in an analysis of variance aimed at determining the
      variances of repeatability and reproducibility. The results showed that RT-qPCRs
      had excellent sensitivity and specificity in the detection of RNA of the Alagoas
      vesiculovirus. The validation parameters showed low coefficients of variation and
      were equivalent to those found in other validation studies, indicating that the
      tests presented excellent repeatability and reproducibility.

PMID- 29601845
TI  - The evolution, distribution and diversity of endogenous circoviral elements in
      vertebrate genomes.
AB  - Circoviruses (family Circoviridae) are small, non-enveloped viruses that have
      short, single-stranded DNA genomes. Circovirus sequences are frequently recovered
      in metagenomic investigations, indicating that these viruses are widespread, yet
      they remain relatively poorly understood. Endogenous circoviral elements (CVe)
      are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe
      are a useful source of information about the biology and evolution of
      circoviruses. In this study, we screened 362 vertebrate genome assemblies in
      silico to generate a catalog of CVe loci. We identified a total of 179 CVe
      sequences, most of which have not been reported previously. We show that these
      CVe loci reflect at least 19 distinct germline integration events. We determine
      the structure of CVe loci, identifying some that show evidence of potential
      functionalization. We also identify orthologous copies of CVe in snakes, fish,
      birds, and mammals, allowing us to add new calibrations to the timeline of
      circovirus evolution. Finally, we observed that some ancient CVe group robustly
      with contemporary circoviruses in phylogenies, with all sequences within these
      groups being derived from the same host class or order, implying a hitherto
      underappreciated stability in circovirus-host relationships. The openly available
      dataset constructed in this investigation provides new insights into circovirus
      evolution, and can be used to facilitate further studies of circoviruses and CVe.

PMID- 29601847
TI  - Repeated peripheral administration of lipidized prolactin-releasing peptide
      analog induces c-fos and FosB expression in neurons of dorsomedial hypothalamic
      nucleus in male C57 mice.
AB  - Previous studies indicate that hypothalamic prolactin-releasing peptide (PrRP),
      signaling via GPR10 and neuropeptide FF2 receptor, is involved in energy
      homeostasis, stress responses, and cardiovascular regulation. Energy homeostasis
      depends on the balance between food intake regulation and energy expenditure, in
      which the hypothalamus plays a key role. The lipidization of PrRP31 with
      palmitoyl acid allows it to produce its anorexigenic effect after repeated
      peripheral administration and to reduce body weight and improve metabolic
      parameters in diet-induced obese (DIO) mice. The aim of this study was to reveal
      the transient and long-lasting changes in neuronal activity via c-Fos and FosB
      immunohistochemistry in brain nuclei related to food intake regulation and energy
      homeostasis during the first days of treatment with a newly designed lipidized
      analog of PrRP31 (palm11-PrRP31) with promising antiobesity effects. The data
      revealed that the anorexigenic effect of repeated application of palm11-PrRP31
      was associated with delayed but gradually significantly reduced cumulative food
      intake in mice as well as with a significant reduction in their body weight.
      Moreover, while the repeated application of palm11-PrRP31 was associated with a
      significant reduction in acute cell activity in the paraventricular hypothalamic
      nucleus (PVN) and nucleus of the solitary tract (NTS) compare to its acute
      treatment, both acute and long-lasting cell activity in the dorsomedial
      hypothalamic nucleus (DMN) were increased. The data indicate that DMN neurons
      might be tonically activated after repeated administration of lipidized PrRP
      analogs that may be associated with the process of long-term adaptation to
      modified energy homeostasis.

PMID- 29601846
TI  - Burden of caregiving after a child's in-hospital cardiac arrest.
AB  - OBJECTIVE: To describe caregiver burden among those whose children survive in
      hospital cardiac arrest and have high risk of neurologic disability, and explore
      factors associated with burden during the first year post-arrest. METHODS: The
      study is a secondary analysis of the Therapeutic Hypothermia after Paediatric
      Cardiac Arrest In-Hospital (THAPCA-IH) trial. 329 children who had an in-hospital
      cardiac arrest, chest compressions for >2 min, and mechanical ventilation after
      return of circulation were recruited to THAPCA-IH. Of these, 155 survived to one
      year, and caregivers of 138 were assessed for burden. Caregiver burden was
      assessed at baseline, and 3 and 12 months post-arrest using the Infant Toddler
      Quality of Life Questionnaire for children <5 years old and the Child Health
      Questionnaire for children >5 years. Child functioning was assessed using the
      Vineland Adaptive Behaviour Scales Second Edition (VABS-II), the Paediatric
      Overall Performance Category (POPC) and Paediatric Cerebral Performance Category
      (PCPC) scales, and caregiver perception of global functioning. RESULTS: Of 138
      children, 77 (55.8%) were male, 77 (55.8%) were white, and 109 (79.0%) were <5
      years old at the time of arrest. Caregiver burden was greater than reference
      norms at all time points. Worse POPC, PCPC and VABS-II scores at 3 months post
      arrest were associated with greater caregiver burden at 12 months. Worse global
      functioning at 3 months was associated with greater burden at 12 months for
      children <5 years. CONCLUSIONS: Caregiver burden is substantial during the first
      year after paediatric in-hospital cardiac arrest, and associated with the extent
      of the child's neurobehavioural dysfunction.

PMID- 29601848
TI  - Food safety using NMR-based metabolomics: Assessment of the Atlantic bluefin
      tuna, Thunnus thynnus, from the Mediterranean Sea.
AB  - Seafood is a valuable component of human diet because of its nutritional
      properties. The Atlantic bluefin tuna Thunnus thynnus is a scombroid fish highly
      appreciated as seafood worldwide. Being a top pelagic predator, concerns have
      been raised over human health risks due to its consumption. Therefore, herein it
      was comprehensively evaluated the health status and potential metabolite shifts
      between sexes of bluefin tuna from the Mediterranean Sea, proved to bioaccumulate
      environmental obesogens, namely polychlorinated biphenyls (PCBs) and
      organochlorine pesticides (OCPs) at hepatic level. To this aim, nuclear magnetic
      resonance (NMR)-based metabolomics was applied on liver of post-spawning tuna.
      Findings from this study pointed out that hepatic bioaccumulation of PCBs and
      OCPs induced differential metabolic disturbances between sexes, attributable to
      the reproductive stage at which tuna were caught. Alterations were mainly found
      in energy-producing metabolic pathways (with changes in acetate, acetoacetate,
      malonate, and lactate), amino acid (with changes in BCAA, alanine, sarcosine, and
      tyrosine), and lipid (with changes in choline and phosphocholine) metabolism,
      with activation of fatty acids biosynthesis and ketogenesis in male tuna.
      Overall, according to the current European legislation on maximum levels of
      contaminants in seafood, the consumption of bluefin tuna does not represent a
      risk for human health.

PMID- 29601849
TI  - Tolerance response and metabolism of acetic acid by biodetoxification fungus
      Amorphotheca resinae ZN1.
AB  - Removal of acetic acid from pretreated lignocellulose biomass is an important
      step for the consequent fermentation on production of cellulosic ethanol and
      biobased chemicals. This study elucidates the biological metabolism and tolerance
      response of acetic acid by a widely used biodetoxification fungus Amorphotheca
      resinae ZN1. Acetic acid is consumed as a prior substrate to glucose and xylose
      by A. resinae ZN1, and the consumption is highly accelerated by solid state
      culture. Acetic acid is metabolized through the tricarboxylic acid (TCA) cycle
      when glucose exists in the medium, while through the two cycles of both the TCA
      cycle and glyoxylate cycle when there is no sugar in the medium. The tolerance
      response of A. resinae ZN1 to acetic acid includes various biological processes
      such as activation of ions transport, increase in amino acids uptake and
      biosynthesis, as well as induction of ergosterol biosynthesis and ATP generation.
      The study provided important basis for the future biodetoxification strain
      modification for enhanced acetic acid removal.

PMID- 29601850
TI  - miR-326 regulates HbF synthesis by targeting EKLF in human erythroid cells.
AB  - Haploinsufficiency of erythroid Kruppel-like factor (EKLF/KLF1) has been shown
      recently to ameliorate the clinical severity of beta-thalassemia by increased
      expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role
      of EKLF in regulating HbF are of great interest but remain incompletely
      understood. In this study, we used a combination of in silico, in vitro, and in
      vivo approaches to identify microRNAs (miRs) involved in EKLF regulation and to
      validate the role of miR-326 in HbF modification. We found that miR-326
      suppresses EKLF expression directly by targeting its 3' untranslated region. miR
      326 overexpression in K562 cells or CD34+ hematopoietic progenitor cells resulted
      in reduced EKLF protein levels and was associated with elevated expression of
      gamma-globin, whereas inhibition of physiological miR-326 levels increased EKLF
      and thus reduced gamma-globin expression. Moreover, miR-326 expression is
      positively correlated with HbF levels in beta-thalassemia patients. Our results
      suggest that miR-326 plays a key role in regulating EKLF expression and in
      modifying the HbF level, which may provide a new strategy for activating HbF in
      individuals with beta-thalassemia or sickle cell disease.

PMID- 29601851
TI  - MicroRNA-155 expression and function in AML: An evolving paradigm.
AB  - Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire
      multiple, recurrent genetic and epigenetic changes that result in dysregulated
      proliferation. Acute leukemia is the most common form of pediatric cancer, with
      AML accounting for ~20% of all leukemias in children. The genomic aberrations
      that drive AML inhibit myeloid differentiation and activate signal transduction
      pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide)
      noncoding RNAs that posttranscriptionally suppress the expression of specifically
      targeted transcripts, are also frequently dysregulated in AML, which may prove
      useful for the purposes of disease classification, prognosis, and future
      therapeutic approaches. MicroRNA expression profiles are associated with patient
      prognosis and responses to standard chemotherapy, including predicting therapy
      resistance in AML. miR-155 is the primary focus of this review because it has
      been repeatedly associated with poorer survival across multiple cohorts of adult
      and pediatric AML. We discuss some novel features of miR-155 expression in AML,
      in particular how the levels of expression can critically influence function.
      Understanding the role of microRNAs in AML and the ways in which microRNA
      expression influences AML biology is one means to develop novel and more targeted
      therapies.

PMID- 29601852
TI  - Gene variants in the NF-KB pathway (NFKB1, NFKBIA, NFKBIZ) and their association
      with type 2 diabetes and impaired renal function.
AB  - The NF-kappaB pathway might play a role in the pathogenesis of renal disease and
      type 2 diabetes (T2DM). Our aim was to determine whether common polymorphisms in
      NF-kappaB genes were associated with impaired renal function and T2DM in a cohort
      of healthy elderly individuals. We studied 487 individuals, all Caucasian and
      aged 65-85 years. A total of 104 (21%) had impaired renal function (estimated
      glomerular filtration rate, eGFR < 60) and 146 (30%) were classified as
      diabetics. The genotypes of 4 common variants were determined through PCR-RFLP or
      fluorescent capillary electrophoresis. The NFKB1 variants were significantly
      associated with T2DM: rs7667496 p = 0.01, OR = 1.68; and rs28362491 p = 0.02, OR
      = 1.67. They remained significantly associated in a multiple logistic regression
      with age, gender, hypertension, body mass index, and cholesterol. There was a
      trend toward the association of these variants with eGFR < 60. The two NFKB1
      variants were in linkage disequilibrium (D' = -0.86), and homozygous for the two
      non-risk alleles (rs7667496 CC + rs28362491 II), were significantly more common
      in the non-diabetics (p = 0.02). In our cohort the NFKB1 variation was an
      independent risk factor for developing T2DM. Additional studies to confirm this
      association are of special interest, as well as studies to give a functional
      explanation to the genetic association.

PMID- 29601853
TI  - Predictors of cognitive impairment assessed by Mini Mental State Examination in
      community-dwelling older adults: relevance of the step test.
AB  - BACKGROUND: Several predictors of cognitive impairment assessed by Mini Mental
      State Examination (MMSE) have previously been identified. However, which
      predictors are the most relevant and what is their effect on MMSE categories
      remains unclear. METHODS: Cross-sectional and longitudinal study using data from
      1116 older adults (72.6 +/- 5.6 years, 579 female), 350 of whom were followed for
      7 years. At baseline, the following variables were collected: personal data,
      marital status, occupation, anthropometric measures, risk factors, previous
      cardiovascular events, self-rated health and physical activity during the last
      week. Furthermore, routine laboratory tests, abdominal echography and a step test
      (with measurement of the time needed to ascend and descend two steps 20 times)
      were performed. The associations of these variables with cross-sectional
      cognitive deficit (MMSE < 24) and longitudinal cognitive decline (decrease of
      MMSE score over 7 years of follow-up) were investigated using logistic regression
      models. RESULTS: Cross-sectional cognitive deficit was independently associated
      with school education <= 5 years, prolonged step test duration, having been blue
      collar or housewife (P <= 0.0001 for all) and, with lower significance, with
      advanced age, previous stroke and poor recent physical activity (P < 0.05).
      Longitudinal cognitive decline was mainly associated with step test duration (P =
      0.0001) and diastolic blood pressure (P = 0.0002). The MMSE categories mostly
      associated with step test duration were orientation, attention, calculation and
      language, while memory appeared to be poorly or not affected. CONCLUSIONS: In our
      cohort of older adults, step test duration was the most relevant predictor of
      cognitive impairment.

PMID- 29601854
TI  - Patients with core antibody positive and surface antigen negative Hepatitis B
      (anti-HBc+, HBsAg-) on anti-TNF therapy have a low rate of reactivation.
AB  - Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation
      of Hepatitis B virus (HBV) is associated with immunosuppressive agents and
      biologics such as anti-TNF. There are limited data and differing guidelines for
      patients with negative hepatitis B surface antigen (HBsAg-) but positive antibody
      to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and
      need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation
      in a single-center retrospective cohort study of 120 HBsAg-, anti-HBc+ patients
      on anti-TNF, totaling 346.6 patient years. One patient (0.8%) who had a
      detectable VL (<20 IU) prior to starting anti-TNF had reactivation of HBV with
      sero-conversion to positive HBsAg. Three patients (2.5%) had undetectable HBV VL
      prior to anti-TNF and developed detectable VL while on anti-TNF. In conclusion,
      there was a low rate of HBV reactivation or development of detectable HBV DNA in
      HBsAg-, anti-HBc+ patients on anti-TNF.

PMID- 29601855
TI  - EGR-1 Expression in Catecholamine-synthesizing Neurons Reflects Auditory Learning
      and Correlates with Responses in Auditory Processing Areas.
AB  - Distinguishing between familiar and unfamiliar individuals is an important task
      that shapes the expression of social behavior. As such, identifying the neural
      populations involved in processing and learning the sensory attributes of
      individuals is important for understanding mechanisms of behavior. Catecholamine
      synthesizing neurons have been implicated in sensory processing, but relatively
      little is known about their contribution to auditory learning and processing
      across various vertebrate taxa. Here we investigated the extent to which
      immediate early gene expression in catecholaminergic circuitry reflects
      information about the familiarity of social signals and predicts immediate early
      gene expression in sensory processing areas in songbirds. We found that male
      zebra finches readily learned to differentiate between familiar and unfamiliar
      acoustic signals ('songs') and that playback of familiar songs led to fewer
      catecholaminergic neurons in the locus coeruleus (but not in the ventral
      tegmental area, substantia nigra, or periaqueductal gray) expressing the
      immediate early gene, EGR-1, than playback of unfamiliar songs. The pattern of
      EGR-1 expression in the locus coeruleus was similar to that observed in two
      auditory processing areas implicated in auditory learning and memory, namely the
      caudomedial nidopallium (NCM) and the caudal medial mesopallium (CMM), suggesting
      a contribution of catecholamines to sensory processing. Consistent with this, the
      pattern of catecholaminergic innervation onto auditory neurons co-varied with the
      degree to which song playback affected the relative intensity of EGR-1
      expression. Together, our data support the contention that catecholamines like
      norepinephrine contribute to social recognition and the processing of social
      information.

PMID- 29601857
TI  - Predicting Ion Mobility-Mass Spectrometry trends of polymers using the concept of
      apparent densities.
AB  - Ion Mobility (IM) coupled to Mass Spectrometry (MS) has been used for several
      decades, bringing a fast separation dimension to the MS detection. IM-MS is a
      convenient tool for structural elucidation. The folding of macromolecules is
      often assessed with the support of computational chemistry. However, this
      strategy is strongly dependent on computational initial guesses. Here, we propose
      the analysis of the Collision Cross-Section (CCS) trends of synthetic
      homopolymers based on a fitting method which does not rely on computational
      chemistry a prioris of the three-dimensional structures. The CCS trends were
      evaluated as a function of the polymer chain length and the charge state. This
      method is also applicable to mobility trends. It leads to two parameters
      containing all information available through IM(-MS) measurements. One parameter
      can be interpreted as an apparent density. The second parameter is related to the
      shape of the ions and leads us to introduce the concept of trends with constant
      apparent density. Based on the two fitting parameters, a method for IM trend
      predictions is elaborated. Experimental deviations from the predictions
      facilitate detecting structural rearrangements and three-dimensional structure
      differences of the cationized polymer ions. This leads for instance to an easy
      identification and prediction of the presence of different polymer topologies in
      complex polymer mixtures. The classification of predicted trends could as well
      allow for software-assisted data processing. Finally, we suggest the link between
      the CCS trends of homopolymers and those obtained from (monodisperse)
      biomolecules to interpret potential folding differences during IM-MS studies.

PMID- 29601856
TI  - Light-optimized growth of cyanobacterial cultures: Growth phases and productivity
      of biomass and secreted molecules in light-limited batch growth.
AB  - Cyanobacteria are photosynthetic microorganisms whose metabolism can be modified
      through genetic engineering for production of a wide variety of molecules
      directly from CO2, light, and nutrients. Diverse molecules have been produced in
      small quantities by engineered cyanobacteria to demonstrate the feasibility of
      photosynthetic biorefineries. Consequently, there is interest in engineering
      these microorganisms to increase titer and productivity to meet industrial
      metrics. Unfortunately, differing experimental conditions and cultivation
      techniques confound comparisons of strains and metabolic engineering strategies.
      In this work, we discuss the factors governing photoautotrophic growth and
      demonstrate nutritionally replete conditions in which a model cyanobacterium can
      be grown to stationary phase with light as the sole limiting substrate. We
      introduce a mathematical framework for understanding the dynamics of growth and
      product secretion in light-limited cyanobacterial cultures. Using this framework,
      we demonstrate how cyanobacterial growth in differing experimental systems can be
      easily scaled by the volumetric photon delivery rate using the model organisms
      Synechococcus sp. strain PCC7002 and Synechococcus elongatus strain UTEX2973. We
      use this framework to predict scaled up growth and product secretion in 1L
      photobioreactors of two strains of Synechococcus PCC7002 engineered for
      production of l-lactate or L-lysine. The analytical framework developed in this
      work serves as a guide for future metabolic engineering studies of cyanobacteria
      to allow better comparison of experiments performed in different experimental
      systems and to further investigate the dynamics of growth and product secretion.

PMID- 29601858
TI  - Applications of Gene Editing Technologies to Cellular Therapies.
AB  - Hematologic malignancies are characterized by genetic heterogeneity, making
      classic gene therapy with a goal of correcting 1 genetic defect ineffective in
      many of these diseases. Despite initial tribulations, gene therapy, as a field,
      has grown by leaps and bounds with the recent development of gene editing
      techniques including zinc finger nucleases, transcription activator-like effector
      nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR)
      sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9. These
      novel technologies have been applied to efficiently and specifically modify
      genetic information in target and effector cells. In particular, CRISPR/Cas9
      technology has been applied to various hematologic malignancies and has also been
      used to modify and improve chimeric antigen receptor-modified T cells for the
      purpose of providing effective cellular therapies. Although gene editing is in
      its infancy in malignant hematologic diseases, there is much room for growth and
      application in the future.

PMID- 29601859
TI  - Perfluoroalkylated substances (PFAS) affect neither estrogen and androgen
      receptor activity nor steroidogenesis in human cells in vitro.
AB  - The perfluoroalkylated substances (PFAS) perfluorooctanesulfonic acid (PFOS) and
      perfluorooctanoic acid (PFOA) are used for the fabrication of water- and dirt
      repellent surfaces. The use of PFOS and PFOA was restricted due to their
      reprotoxic properties and their environmental persistence. Therefore, industry
      switches to alternative PFAS, however, in contrast to PFOA and PFOS only few
      toxicological data are available for their substitutes. The molecular
      mechanism(s) underlying reproductive toxicity of PFOA and PFOS are largely
      unknown. Here, the endocrine properties of PFOA, PFOS, and of six substitutes
      including perfluorohexanesulfonic acid (PFHxS), perfluorobutanesulfonic acid
      (PFBS), perfluorohexanoic acid (PFHxA), perfluorobutanoic acid (PFBA), ammonium
      perfluoro(2-methyl-3-oxahexanoate) (PMOH), and 3H-perfluoro-3-[(3-methoxypropoxy)
      propanoic acid] (PMPP) were examined in vitro by using human cell lines such as
      MCF-7, H295R, LNCaP and MDA-kb2. PFOA, PFOS and PMOH enhanced 17beta-estradiol
      stimulated estrogen receptor beta activity, and PFOS, PMOH, PFHxA and PFBA
      enhanced dihydrotestosterone-stimulated androgen receptor activity. In the H295R
      steroidogenesis assay, PFOA and PFOS slightly enhanced estrone secretion, and
      progesterone secretion was marginally increased by PFOA. All these effects were
      only observed at concentrations above 10 MUM, and none of the PFAS displayed any
      effect on any of the molecular endocrine endpoints at concentrations of 10 MUM or
      below. Thus, as the blood serum concentrations of the different PFAS in the
      general Western population are in the range of 10 nM or below, the results
      suggest that PFAS might not exert endocrine effects in humans at exposure
      relevant concentrations according to the molecular endpoints examined in this
      study.

PMID- 29601860
TI  - Urinary excretion of heptanones, heptanoles and 2,5-heptanedione after controlled
      acute exposure of volunteers to n-heptane.
AB  - A lack of well-established parameters and assessment values currently impairs
      biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we
      collected information on urinary n-heptane metabolite concentrations and the time
      course of metabolite excretion. Relationships between external and internal
      exposure were analysed to investigate the suitability of selected metabolites to
      reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19-38 years,
      median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot
      urine samples of the volunteers, collected before exposure and during the
      following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2,5-dione, 1-ol, 2
      ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas
      chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre
      exposure concentrations between <0.5 (3-one) and 82.9 MUg/L (4-one), exposure
      increased the concentrations for all parameters except for 4-one. Median post
      exposure concentrations ranged up to 840.4 MUg/L (2-ol) and decreased with half
      lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05)
      revealed weak to moderate associations of volume related metabolite excretion
      with external exposure for 2-one, 3-one and 2,5-dione (R = 0.332-0.753). Heptanol
      excretion was moderately associated with exposure (R >= 0.509) only after
      creatinine adjustment. Lacking association with external exposure impedes the use
      of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive
      indicators of exposure if creatinine correction is applied. By providing
      fundamental data on a panel of eight potential heptane metabolites, our study can
      help to promote biological monitoring of n-heptane exposure.

PMID- 29601862
TI  - Phagocytes as central players in the defence against invasive fungal infection.
AB  - Fungal pathogens cause severe and life-threatening infections worldwide. The
      majority of invasive infections occurs in immunocompromised patients and is based
      on acquired as well as congenital defects of innate and adaptive immune
      responses. In many cases, these defects affect phagocyte functions. Consequently,
      professional phagocytes - mainly monocytes, macrophages, dendritic cells and
      polymorphonuclear neutrophilic granulocytes - have been shown to act as central
      players in initiating and modulating antifungal immune responses as well as
      elimination of fungal pathogens. In this review we will summarize our current
      understanding on the role of these professional phagocytes in invasive fungal
      infection to emphasize two important aspects. (i) Analyses on the interaction
      between fungi and phagocytes have contributed to significant new insights into
      phagocyte biology. Important examples for this include the identification of
      pattern recognition receptors for beta-glucan, a major cell wall component of
      many fungal pathogens, as well as the identification of genetic polymorphisms
      that determine individual host responses towards invading fungi. (ii) At the same
      time it was shown that fungal pathogens have evolved sophisticated mechanisms to
      counteract the attack of professional phagocytes. These mechanisms range from
      complete mechanical destruction of phagocytes to exquisite adaptation of some
      fungi to the hostile intracellular environment, enabling them to grow and
      replicate inside professional phagocytes.

PMID- 29601861
TI  - Neutrophil extracellular traps in fungal infection.
AB  - Fungal infections are a continuously increasing problem in modern health care.
      Understanding the complex biology of the emerging pathogens and unraveling the
      mechanisms of host defense may form the basis for the development of more
      efficient diagnostic and therapeutic tools. Neutrophils play a pivotal role in
      the defense against fungal pathogens. These phagocytic hunters migrate towards
      invading fungal microorganisms and eradicate them by phagocytosis, oxidative
      burst and release of neutrophil extracellular traps (NETs). In the last decade,
      the process of NET formation has received unparalleled attention, with numerous
      studies revealing the relevance of this neutrophil function for control of
      various mycoses. Here, we describe NET formation and summarize its role as part
      of the innate immune defense against fungal pathogens. We highlight factors
      influencing the formation of these structures and molecular mechanisms employed
      by fungi to impair the formation of NETs or subvert their antifungal effects.

PMID- 29601863
TI  - Culturing functional pancreatic islets on alpha5-laminins and curative
      transplantation to diabetic mice.
AB  - The efficacy of islet transplantation for diabetes treatment suffers from lack of
      cadaver-derived islets, islet necrosis and long transfer times prior to
      transplantation. Here, we developed a method for culturing mouse and human islets
      in vitro on alpha5-laminins, which are natural components of islet basement
      membranes. Adhering islets spread to form layers of 1-3 cells in thickness and
      remained normoxic and functional for at least 7 days in culture. In contrast,
      spherical islets kept in suspension developed hypoxia and central necrosis within
      16 h. Transplantation of 110-150 mouse islets cultured on alpha5-laminin-coated
      polydimethylsiloxane membranes for 3-7 days normalized blood glucose already
      within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of
      isolated and cultured mouse islets provided further evidence for the adhesion and
      spreading achieved with alpha5-laminin. Our results suggest that use of such in
      vitro expanded islets may significantly enhance the efficacy of islet
      transplantation treatment for diabetes.

PMID- 29601864
TI  - TMEM2: A missing link in hyaluronan catabolism identified?
AB  - Hyaluronan (HA) is a glycosaminoglycan (GAG) composed of repeating disaccharide
      units of glucuronic acid and N-acetylglucosamine. HA is an extremely long,
      unbranched polymer, which often exceeds 106 Da and sometimes reaches 107 Da. A
      feature that epitomizes HA is its rapid turnover; one-third of the total body HA
      is turned over daily. The current model of HA catabolism postulates that high
      molecular weight HA in the extracellular space is first cleaved into smaller
      fragments by a hyaluronidase(s) that resides at the cell surface, followed by
      internalization of fragments and their degradation into monosaccharides in
      lysosomes. Over the last decade, considerable research has shown that the HYAL
      family of hyaluronidases plays significant roles in HA catabolism. Nonetheless,
      the identity of a hyaluronidase responsible for the initial step of HA cleavage
      on the cell surface remains elusive, as biochemical and enzymological properties
      of HYAL proteins are not entirely consistent with those expected of cell surface
      hyaluronidases. Recent identification of transmembrane 2 (TMEM2) as a cell
      surface protein that possesses potent hyaluronidase activity suggests that it may
      be the "missing" cell surface hyaluronidase, and that novel models of HA
      catabolism should include this protein.

PMID- 29601865
TI  - Water-fat separation incorporating spatial smoothing is robust to noise.
AB  - PURPOSE: To develop and evaluate a noise-robust method for reconstruction of
      water and fat images for spoiled gradient multi-echo sequences. METHODS: The
      proposed method performs water-fat separation by using a graph cut to minimize an
      energy function consisting of unary and binary terms. Spatial smoothing is
      incorporated to increase robustness to noise. The graph cut can fail to find a
      solution covering the entire image, in which case the relative weighting of the
      unary term is iteratively increased until a complete solution is found. The
      proposed method was compared to two previously published methods. Reconstructions
      were performed on 16 cases taken from the 2012 ISMRM water-fat reconstruction
      challenge dataset, for which reference reconstructions were provided. Robustness
      towards noise was evaluated by reconstructing images with different levels of
      noise added. The percentage of water-fat swaps were calculated to measure
      performance. RESULTS: At low noise levels the proposed method produced similar
      results to one of the previously published methods, while outperforming the
      other. The proposed method significantly outperformed both of the previously
      published methods at moderate and high noise levels. CONCLUSION: By incorporating
      spatial smoothing, an increased robustness towards noise is achieved when
      performing water-fat reconstruction of spoiled gradient multi-echo sequences.

PMID- 29601866
TI  - Extension of quality-by-design concept to the early development phase of
      pharmaceutical R&D processes.
AB  - Here, we propose the extension of the quality-by-design (QbD) concept to also fit
      the early development phases of pharmaceuticals by adding elements that are
      currently widely applied, but not yet included in the QbD model in a structured
      way. These are the introduction of a 'zero' preformulation phase (i.e., selection
      of drug substance, possible dosage forms and administration routes based on the
      evaluated therapeutic need); building in stakeholders' (industry, patient, and
      regulatory) requirements into the quality target product profile (QTTP); and the
      use of modern quality management tools during the composition and process design
      phase [collecting critical quality attributes (CQAs) and selection of CPPs) for
      (still laboratory-scale) design space (DS) development. Moreover, during
      industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be
      changed; however, we recommend that the existing QbD elements are reconsidered
      and updated after this phase.

PMID- 29601867
TI  - High salt diet can down-regulate TFF2 expression level in gastric mucosa of MGs
      after H. pylori infection.
AB  - This study aimed to elucidate the effect of Helicobacter pylori (H. pylori) and
      high salt diet on Trefoil factor 2 (TFF2) expression level of Mongolian gerbils
      (MGs) gastric mucosa. The results of H. pylori identification and histopathology
      showed that H. pylori infected MGs model was built successfully. According to the
      immunohistochemical staining results, 25% (4/16) of H. pylori infected MGs with
      high salt diet showed high TFF2 expression, which was significantly lower than H.
      pylori infection group 61% (11/18)(P = 0.045). The results suggested that High
      salt diet could down-regulated TFF2 expression level of MGs gastric mucosa
      induced by H. pylori infection.

PMID- 29601868
TI  - Characteristic and mechanism of immobilization effect of Staphylococcus aureus on
      human spermatozoa.
AB  - OBJECTIVE: This study was designed to investigate the impacts of Staphylococcus
      aureus isolated from sperm of male infertility patients, and explore the
      mechanism of the spermatozoa immobilization attributed to S. aureus. METHODS: S.
      aureus MJ015 and MJ163, the representative strains of immobilization positive and
      negative group respectively, were obtained from semen of infertile men. Computer
      aided sperm analysis (CASA) were performed to measure sperm motility.
      Transmission electron microscopy (TEM) was utilized to assess morphological
      alterations of spermatozoa. Two-dimensional gel electrophoresis (2-DE) and liquid
      chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) were undertaken to
      analyse the difference between the secretory proteins of MJ015 and MJ163.
      RESULTS: A highly significant decline in motility of spermatozoa after incubating
      with cultured supernatant of MJ015 by sperm motility measurements, which was not
      observed when co-cultured with the supernatant of MJ163. TEM illustrated that the
      culture supernatant of MJ015 contributed to apparently ultrastructural impairment
      and inhibitory impacts on sperm motility. Various proteins expressed by two
      samples were identified. Data processing and database search preliminarily
      establish a link between four differential proteins and spermatozoal
      immobilization ability. CONCLUSIONS: Our data manifested that the clinical
      isolates of S. aureus have a key role on the motility and morphology of sperm. A
      better correlation between four identified differentially expressed proteins and
      the marked decline of the motility of spermatozoa was established.

PMID- 29601870
TI  - Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin
      metabolism by altering neutral sphingomyelinase activity.
AB  - Previous studies have shown that patients with Guillain-Barre syndrome express
      autoantibodies against ganglioside GM1 (GM1), although its pathogenic
      significance for the development of the disease remains to be elucidated. nSMase2
      is the best characterized neutral sphingomyelinase (nSMase) found in neuronal
      cells. Activation of this enzyme leads to ceramide production, which is a known
      second messenger of the cell-death program in neuronal cells. We have explored
      the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells
      stably transfected with human trk cDNA (PCtrk cells) by determining their effects
      on nSMase2 activity. The data we present here strongly suggest that anti-GM1
      caused a significant change in sphingomyelin content of the membrane fraction in
      PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were
      significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase
      activities remained unchanged. Our results indicate, for the first time, that
      anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell
      membranes.

PMID- 29601869
TI  - d-Serine administration affects nitric oxide synthase 1 adaptor protein and DISC1
      expression in sex-specific manner.
AB  - Antipsychotic medications are inefficient at treating symptoms of schizophrenia
      (SCZ), and N-methyl d-aspartate receptor (NMDAR) agonists are potential
      therapeutic alternatives. As such, these agonists may act on different pathways
      and proteins altered in the brains of patients with SCZ than do antipsychotic
      medications. Here, we investigate the effects of administration of the
      antipsychotic haloperidol and NMDAR agonist d-serine on function and expression
      of three proteins that play significant roles in SCZ: nitric oxide synthase 1
      adaptor protein (NOS1AP), dopamine D2 (D2) receptor, and disrupted in
      schizophrenia 1 (DISC1). We administered haloperidol or d-serine to male and
      female Sprague Dawley rats via intraperitoneal injection for 12 days and
      subsequently examined cortical expression of NOS1AP, D2 receptor, and DISC1. We
      found sex-specific effects of haloperidol and d-serine treatment on the
      expression of these proteins. Haloperidol significantly reduced expression of D2
      receptor in male, but not female, rats. Conversely, d-serine reduced expression
      of NOS1AP in male rats and did not affect D2 receptor expression. d-serine
      treatment also reduced expression of DISC1 in male rats and increased DISC1
      expression in female rats. As NOS1AP is overexpressed in the cortex of patients
      with SCZ and negatively regulates NMDAR signaling, we subsequently examined
      whether treatment with antipsychotics or NMDAR agonists can reverse the
      detrimental effects of NOS1AP overexpression in vitro as previously reported by
      our group. NOS1AP overexpression promotes reduced dendrite branching in vitro,
      and as such, we treated cortical neurons overexpressing NOS1AP with different
      antipsychotics (haloperidol, clozapine, fluphenazine) or d-serine for 24 h and
      determined the effects of these drugs on NOS1AP expression and dendrite
      branching. While antipsychotics did not affect NOS1AP protein expression or
      dendrite branching in vitro, d-serine reduced NOS1AP expression and rescued
      NOS1AP-mediated reductions in dendrite branching. Taken together, our data
      suggest that d-serine influences the function and expression of NOS1AP, D2
      receptor, and DISC1 in a sex-specific manner and reverses the effects of NOS1AP
      overexpression on dendrite morphology.

PMID- 29601871
TI  - Molecular characterization and genetic diversity of avian paramyxovirus type 4
      isolated in South Korea from 2013 to 2017.
AB  - In recent years, avian paramyxovirus type 4 (APMV-4) frequently isolated from
      wild and domestic bird populations particularly waterfowls worldwide. However,
      molecular characteristics and genetic diversity of APMV-4 are uncertain, owing to
      the limited availability of sequence information. A total of 11 APMV-4 strains
      from 9850 fecal, swab, and environmental samples were isolated during the
      surveillance program in wintering seasons of 2013-2017 in South Korea. We
      performed genetic characterization and phylogenetic analysis to investigate the
      genetic diversity and relatedness between isolates from the region. We report
      high APMV-4 genetic diversity (multiple genotypes and sub-genotypes) among wild
      bird and poultry populations in Korea and that the potential virus exchange
      occurs between neighboring countries via wild bird migration. Furthermore, our
      study results suggest the possibility of transcontinental transmission of APMV-4
      between Asia and Europe.

PMID- 29601872
TI  - Spatiotemporal and demographic history of the HIV-1 circulating recombinant form
      CRF31_BC in Brazil.
AB  - CRF31_BC is an HIVs-1 recombinant form very prevalent in the southernmost capital
      city of Brazil, Porto Alegre. Recent studies have been describing a growing
      number of cases of infection by CRF31_BC in other Brazilian cities and countries,
      suggesting a process of expansion of this strain. Aiming to describe the city of
      origin, dispersion routes and demographic history of CRF31_BC, this study
      analyzed all HIV-1 CRF31_BC and Brazilian BC mosaic publicly available sequences.
      CRF31_BC classification was performed by bootscanning and tree reconstruction
      methods. Bayesian phylogeographic and phylodynamic model approaches were used to
      reconstruct the spatiotemporal and demographic history of 95 sequences identified
      as CRF31_BC-like. Porto Alegre was estimated to be the origin and center of the
      dispersion of the CRF31_BC for most of the analyzed locations. However, some
      viral transitions independent from Porto Alegre were observed in other cities
      from the Rio Grande do Sul state and also in other Brazilian states. The
      estimated CRF31_BC epidemic growth rate was similar to subtype C and B in Brazil.
      Our findings suggest that CRF31_BC, although mostly prevalent in south region, is
      circulating nation-wide with some localities presenting autochthonous
      transmissions.

PMID- 29601873
TI  - Homocysteine up-regulates ETB receptors via suppression of autophagy in vascular
      smooth muscle cells.
AB  - The change of autophagy is implicated in cardiovascular diseases (CVDs).
      Homocysteine (Hcy) up-regulates endothelin type B (ETB) receptors in vascular
      smooth muscle cells (VSMCs). However, it is unclear whether autophagy is involved
      in Hcy-induced-up-regulation of ETB receptors in VSMCs. The present study was
      designed to examine the hypothesis that Hcy up-regulates ETB receptors by
      inhibiting autophagy in VSMCs. Hcy treated the rat superior mesenteric artery
      (SMA) without endothelium in the presence and absence of AICAR, rapamycin or
      MHY1485 for 24 h. The contractile responses to sarafotoxin 6c (S6c) (an ETB
      receptor agonist) were studied using a sensitive myograph. Levels of protein
      expression were determined using Western blot analysis. Punctate staining of LC3B
      was exanimated by immunofluorescence using confocal microscopy. The results
      showed that Hcy inhibited AMPK, and activated mTOR, followed by impairing
      autophagy, and increased the levels of ETB receptor protein expression and the
      ETB receptor-mediated contractile responses to S6c in SMA without endothelium.
      However, these effects were reversed by AICAR or rapamycin. Additionally, MHY1485
      up-regulated the AICAR-inhibited ETB receptor-mediated contractile response and
      the levels of ETB receptor protein expression in presence of Hcy. In conclusion,
      this suggested that Hcy up-regulated ETB receptors by inhibiting autophagy in
      VSMCs via AMPK/mTOR signaling pathway.

PMID- 29601874
TI  - Isolating the influences of fluid dynamics on selectin-mediated particle rolling
      at venular junctional regions.
AB  - The objective of this study was to isolate the impact of hydrodynamics on
      selectin-mediated cell rolling in branched microvessels. Significant advancements
      have been made in furthering the understanding of complex interactions between
      biochemical and physical factors in the inflammatory cascade in simplified planar
      geometries. However, few studies have sought to quantify the effects of branched
      configurations and to isolate the effects of associated fluid forces.
      Experimental techniques were developed to perform in vitro adhesion experiments
      in Y-shaped micro-slides. The micro-slides were coated with P-selectin and
      microspheres coated with Sialyl-Lewisx were observed as they rolled in the
      chambers at different wall shear stresses. Study results revealed that
      microsphere rolling velocities and rolling flux were lowest in regions closest to
      the apex of a junctional region and were dependent on both branch angle and wall
      shear stress. The regions closest to the junctional region were shown to have low
      bulk flow velocities and shear stresses using computational fluid dynamics (CFD)
      modeling. Collectively, the study demonstrates that despite the presence of a
      uniform coating of P-selectin, hydrodynamic factors associated with the chamber
      geometry yield non-uniform effects on particle behavior. These findings could
      explain why cells have been observed to preferentially adhere or transmigrate
      near junctional regions. Future characterization of inflammatory processes in
      microvascular network configurations is therefore crucial for furthering our
      fundamental understanding of inflammation.

PMID- 29601875
TI  - Microvascular abnormalities in dry eye patients.
AB  - This study was conducted to evaluate conjunctival blood flow velocities and
      microvascular network density in patients with dry eye disease (DED). Twenty-five
      patients with DED and 25 healthy controls were recruited. The microvasculature
      and microcirculation of the temporal bulbar conjunctiva of the right eyes were
      assessed using a functional slit-lamp biomicroscope. Vascular variables included
      blood flow velocity (BFV), blood flow rate (BFR), microvascular network density
      and vessel diameter. A fractal analysis was performed using the box counting
      method to measure the fractal dimension (Dbox) representing the vessel density.
      The bulbar BFV was 0.59 +/- 0.09 mm/s in the DED group and 0.47 +/- 0.12 in the
      control group (P < 0.001). BFR was 169.5 +/- 1.8 in the DED group compared to the
      control group (107.2 +/- 49.6) (P < 0.001). Dbox was higher in DED patients (1.65
      +/- 0.04) than controls (1.60 +/- 0.07, P < 0.05). Moreover, the vessel diameter
      was larger in the DED group (21.8 +/- 1.8 MUm) compared with controls (17.9 +/-
      2.2 MUm, P < 0.001). Dbox was positively related with ocular surface disease
      index (OSDI) in patients with DED (r = 0.54, P = 0.008). Microvascular
      alterations were found in the bulbar conjunctiva of DED patients, including
      increased blood flow velocity, higher vessel density and larger vessel diameter.

PMID- 29601876
TI  - Isolation, purification and characterization of exopolysaccharide produced by
      Leuconostoc pseudomesenteroides YF32 from soybean paste.
AB  - A water-soluble exopolysaccharide (EPS)-producing strain YF32 was isolated from
      soybean paste, which was then identified as Leuconostoc pseudomesenteroides.
      After culturing the strain in Man-Rogosa-Sharpe (MRS) medium containing 5%
      sucrose at 30 degrees C for 48h, the EPS was purified, and a yield of 12.5g/L was
      achieved. The weight-average molecular weight (Mw) was 5.54*106Da by high
      performance size-exclusion chromatography (HPSEC). The structural
      characterization of the purified EPS was determined by gas chromatography (GC),
      Fourier transform infrared (FT-IR), 1H, 13C nuclear magnetic resonance (NMR)
      spectroscopy. The results demonstrated that the exopolysaccharide was glucan with
      a peak, a linear backbone composed of consecutive alpha-(1->6)-linked d
      glucopyranose units. No branching was observed in the dextran structure. The
      degradation temperature (Td) of EPS was 307.62 degrees C, which suggested that
      dextran exhibited high thermal stability. YF32 dextran also showed high water
      solubility and emulsibility. All results suggested that dextran has the potential
      to be applied in food fields as a food additive.

PMID- 29601877
TI  - A design optimization study on synthesized nanocrystalline cellulose, evaluation
      and surface modification as a potential biomaterial for prospective biomedical
      applications.
AB  - In the present study, nanocrystalline cellulose (NCC) was prepared via acid
      hydrolysis and synthesis parameters were optimized via response surface modelling
      with a determined maximum NCC yield of 43.8%. The optimized NCC sample was
      subsequently surface modified via epichlorohydrin-mediated amination forming
      aminated nanocrystalline cellulose (A-NCC) with an amine content calculated as
      1500MUmol/g. The average particle size and zeta potential were determined 100nm
      and 325nm for NCC and A-NCC, respectively. Structural properties were analyzed by
      FTIR, TEM and XRD techniques. The obtained A-NCC as final product depicted a pKa
      value of 10.86+/-0.07 demonstrating favourable protonation of amine groups at
      physiological pH allowing the material to be suitable for prospective application
      in drug delivery and tissue engineering.

PMID- 29601878
TI  - Phenoloxidase activation, antimicrobial, and antibiofilm properties of beta
      glucan binding protein from Scylla serrata crab hemolymph.
AB  - In this study, we purified beta-GBP from hemolymph of Scylla serrata crabs using
      affinity chromatography. The purified S. serrata beta-GBP (Ss-beta-GBP) had
      100kDa molecular mass in the SDS-PAGE. MALDI-TOF/TOF analysis was conducted,
      revealing that the purified 100kDa protein had 96% similarity with beta-GBP of
      Astacus leptodactylus. Ss-beta-GBP was characterized using high-performance
      liquid chromatography (HPLC), X-ray diffraction (XRD) analysis, circular
      dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy, which
      confirmed the structure of the Ss-beta-GBP. The purified Ss-beta-GBP was
      functionally analyzed by yeast agglutination and phagocytic reaction assays.
      Moreover, the PO enhancing ability of Ss-beta-GBP was evidenced through PO
      activity. Specifically, the antibacterial activity of the Ss-beta-GBP against
      Gram-positive (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative
      (Escherichia coli and Pseudomonas aeruginosa) bacteria was evaluated by
      determining its minimum inhibitory concentration (MIC)<60MUg/ml for all tested
      species. Furthermore, the antibiofilm efficacy of Ss-beta-GBP at 50 and 100MUg/ml
      was outlined using light microscopy and confocal laser scanning microscopy
      (CLSM). Bacterial viability assays also outlined the dose-dependent activity of
      Ss-beta-GBP based on the ratio of live/dead bacterial cells. The results of this
      study revealed that crab-borne Ss-beta-GBP might be widely used to suppress the
      growth of pathogenic bacteria.

PMID- 29601879
TI  - Thermal restraint of a bacterial exopolysaccharide of shallow vent origin.
AB  - To dynamically characterize the thermal properties of the fructose-rich
      exopolysaccharide (EPS1-T14), produced by the marine thermophilic Bacillus
      licheniformis T14, the Attenuated Total Reflectance Fourier Transform Infra-Red
      spectroscopy was coupled to variable temperature ranging from ambient to 80
      degrees C. The spectra were analyzed by the following innovative mathematical
      tools: i) non-ideal spectral deviation, ii) OH-stretching band frequency center
      shift, iii) spectral distance, and iv) wavelet cross-correlation analysis. The
      thermal restraint analysis revealed that the whole EPS1-T14 system possessed high
      stability until 80 degrees C, and suggested that fucose was mainly involved in
      the EPS1-T14 thermal stability, whereas glucose was responsible for its molecular
      flexibility. Our results provide novel insights into the thermal stability
      properties of the whole EPS1-T14 and into the role of its main monosaccharidic
      units. As a new biopolymer, the thermostable EPS1-T14 could be used in
      traditional biotechnology fields and in new biomedical areas, as nanocarriers,
      requiring high temperature processes.

PMID- 29601880
TI  - Dual responsive aerogel made from thermo/pH sensitive graft copolymer alginate-g
      P(NIPAM-co-NHMAM) for drug controlled release.
AB  - Alginate was grafted with NIPAM and NHMAM successfully, and a new responsive
      copolymer, alginate-g-P(NIPAM-co-NHMAM), was obtained. A novel dual responsive
      polysaccharide-based aerogel with thermo/pH sensitive properties was designed
      from the copolymer as drug controlled release system. The chemical structure of
      the copolymer was characterized by FT-IR and 1H NMR. Lower critical solution
      temperature (LCST) of the copolymer covered a wide temperature range from 27.6 
      degrees C to 42.2  degrees C, which could be adjusted with changing the ratio
      between NIPAM and NHMAM. The dual responsive aerogel had a three-dimensional
      network structure. As a drug controlled release system, the aerogel was high
      responsive to both temperature and pH with drug loading efficiency up to 13.24%.
      Above LCST, the aerogel had a faster drug release, and drug was completely
      released in neutral environment, while the drug release was obstructed in acid
      environment. Furthermore, the drug release mechanism of the aerogel was
      illuminated. These results indicated that the dual responsive aerogel was a
      promising candidate for drug carriers.

PMID- 29601881
TI  - Effect of different types and concentrations of emulsifier on the characteristics
      of kappa-carrageenan films.
AB  - kappa-Carrageenan films derived from Euchema cottoni containing different types
      and concentrations of emulsifier were developed. Film formation without the
      addition of emulsifier was used as a control. The physical, mechanical, optical
      and microstructural properties of these films were determined. Different types of
      emulsifiers (Tween 20, Tween 40 and Tween 80) exerted significant effects
      (P<=0.05) on the thickness, moisture content and opacity of the films.
      Additionally, Tween 20 and Tween 40 with concentrations from 0.1 to 0.5% (v/v)
      significantly (P<=0.05) improved the tensile strength of the films, ranging from
      7.35 to 13.83MPa. The water vapor permeability of the carrageenan films was
      significantly (P<=0.05) affected by both factors. Increasing the emulsifier
      concentration also caused an increment in the number of lipid droplets
      contributing to a smooth surface. Therefore, this study suggests that different
      types and concentrations of emulsifiers play essential roles in determining the
      physical properties of carrageenan films.

PMID- 29601882
TI  - A novel serine protease from strawberry (Fragaria ananassa): Purification and
      biochemical characterization.
AB  - In this study, a protease enzyme was purified from strawberry by using Sepharose
      4B-l-tyrosine-p-amino benzoic acid affinity chromatography. The molecular weight
      of pure protease was determined 65.8 kDa by SDS-PAGE. The single band observed on
      the gel showed that the enzyme had a single polypeptide chain and was
      successfully purified. Purification of the protease by the chromatographic method
      resulted in a 395.6-fold increase in specific activity (3600 U/mg). Optimum pH
      and temperature for the enzyme were 6 and 40  degrees C, respectively. The
      protease was stable at a wide temperature range of 40 to 70  degrees C and a pH
      range of 3.0 to 9.0. Co2+ ions stimulated protease activity very strongly. Cu2+,
      Hg2+, Cd2+ and Mn2+ ions significantly inhibited protease activity. While 2
      propanol completely inhibited the enzyme, the enzyme maintained its activity
      better in the presence of ethanol and methanol. The strawberry protease showed
      the highest specificity towards hemoglobin among all the natural substrates
      tested. The specificity of the enzyme towards synthetic substrates was also
      investigated and it was concluded that it has broad substrate specificity. The
      obtained results indicated that this purified protease was highly-likely a serine
      protease and its activity was significantly affected by the presence of metal
      ions.

PMID- 29601883
TI  - Synthesis and antidiabetic activity of selenium nanoparticles in the presence of
      polysaccharides from Catathelasma ventricosum.
AB  - Selenium nanoparticles (SeNPs) were prepared by adding Catathelasma ventricosum
      polysaccharides (CVPs) to the redox system of selenite and ascorbic acid. Taking
      particle size as an investigation index, the optimal synthesis conditions of CVPs
      SeNPs were obtained by orthogonal test. Herein, the diameter, morphology, and
      stability of the CVPs-SeNPs were characterized by dynamic light scattering (DLS)
      and transmission electron microscopy (TEM). Moreover, the antidiabetic activities
      of CVPs-SeNPs were evaluated by STZ (streptozocin)-induced diabetic mice. The
      obtained results showed that, optimum synthesis conditions of CVPs-SeNPs were:
      ultrasonic time 60min, concentration of Vc 0.04M, reaction time 2h, pH7.0. Under
      these conditions, mean diameter of the synthesized CVPs-SeNPs was around 49.73nm.
      TEM of CVPs-SeNPs prepared in optimal conditions showed individual and spherical
      nanostructure. CVPs-SeNPs (particle size of about 50nm) could be stable for
      approximately 3months at 4 degrees C, but only 1month at 25 degrees C. The
      results on serum profiles and antioxidant enzymes levels revealed that CVPs-SeNPs
      had a potential antidiabetic effect. In addition, CVPs-SeNPs showed significantly
      higher antidiabetic activity (p<0.05) than other selenium preparations such as
      SeNPs, selenocysteine, sodium selenite.

PMID- 29601884
TI  - Fabrication of regenerated wool keratin/polycaprolactone nanofiber membranes for
      cell culture.
AB  - Regenerated wool keratin is a promising natural material for tissue engineering.
      In the present study, l-cysteine redox method was performed to extract keratin
      from wool. Then the different ratios of keratins blended with polycaprolactone
      (PCL) in formic acid were electrospun to produce nanofibrous membrane. The
      morphology, biodegradation degree in phosphate buffer saline (PBS) and cell
      culture were closely investigated. It is found that adding keratin to the PCL
      nanofiber can improve the hydrophilicity of the as-spun nanofiber mats and then
      promote the cell adhesion and proliferation of the composite nanofibrous mats.
      The nanofiber membrane with the highest hydrophilicity had the highest cellular
      compatibility.

PMID- 29601885
TI  - An image registration protocol to integrate electrophysiology, MRI and
      neuropathology data in epileptic patients explored with intracerebral electrodes.
AB  - BACKGROUND: Several attempts have been made to coregister in vivo MRI with the
      histopathology of surgical samples, aiming to validate new MRI biomarkers and
      improve the detection of epileptogenic lesions. As a further implementation, we
      propose a method to reconstruct the anatomical localization of the intracerebral
      electrodes on the histological sections, developing a coregistration protocol to
      match the in vivo MRI onto the ex vivo MRI obtained from the surgical specimen.
      NEW METHOD: Since the ex vivo MRI is natively in geometrical correspondence with
      histology slices, the goal of the coregistration process is to compute the
      transform function mapping the clinical MRI space to the ex vivo MRI. Electrodes
      and leads, identified in CT-MRI, can then be segmented and translated onto the
      histological slices. RESULTS: Step-by-step, qualitative visual inspection showed
      an improved matching of the anatomical structures or boundaries and electrodes
      positions between the two modalities. The quantitative evaluation of the
      coregistration protocol reported a mean error ranging between 0.82 and 1.27 mm
      when a sufficient number of landmarks, particularly in the core of the specimen,
      were clearly identified. COMPARISON WITH EXISTING METHODS: Because histology was
      performed according to ex vivo MRI geometry we chose to transform the in vivo
      onto the ex vivo MRI, differently from other methods. CONCLUSIONS: Interesting
      applications of the method will include correlating the locally-generated
      pathological electrical activity with the subtle morphological alterations of the
      tissue, and histologically validating the origin of signal alterations or
      quantitative parameter variations in MRI studies.

PMID- 29601887
TI  - Schizotypal traits and forearm motor control against self-other produced action
      in a bimanual unloading task.
AB  - The present study investigated the relation between schizotypy and motor control
      against self- or other-produced action. We used an unloading task to focus on the
      timing component of anticipatory motor control. In the task, a weight was removed
      from a participants' hand by the participants themselves or by an experimenter
      (voluntary versus imposed unloading). Postural disturbance at the removal timing
      was measured as an index of predictive function in motor control. We hypothesized
      that the postural disturbance in the voluntary unloading would be positively
      related to schizotypal traits; however, the results did not support this theory.
      The results showed almost zero correlation between the schizotypy scores and the
      postural disturbance in the voluntary unloading condition. In contrast, the
      schizotypy scores positively correlated with the postural disturbance in the
      imposed unloading condition. These findings were replicated across two
      participant groups and two schizotypy scales. Further analyses on subscales of
      the schizotypy questionnaire found moderate levels of positive correlation
      between each subscale for Cognitive-Perceptual and Disorganization factors and
      the disturbance. Accordingly, the present study did not support the idea that non
      pathological individuals with high schizotypal traits have deficits in prediction
      of self-produced actions, at least for a temporal domain. Instead, the results
      suggested that individuals with high schizotypal traits, particularly for the
      positive and disorganization symptoms, are not good at responding to others
      produced actions. The schizophrenic symptoms were discussed in terms of the
      failure in the processes executed after calculating prediction of sensory
      consequences and dysfunction in internal models for "other people".

PMID- 29601886
TI  - A method to assess randomness of functional connectivity matrices.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) allows for the
      measurement of functional connectivity of the brain. In this context, graph
      theory has revealed distinctive non-random connectivity patterns. However, the
      application of graph theory to fMRI often utilizes non-linear transformations
      (absolute value) to extract edge representations. NEW METHOD: In contrast, this
      work proposes a mathematical framework for the analysis of randomness directly
      from functional connectivity assessments. The framework applies random matrix
      theory to the analysis of functional connectivity matrices (FCMs). The developed
      randomness measure includes its probability density function and statistical
      testing method. RESULTS: The utilized data comes from a previous study including
      603 healthy individuals. Results demonstrate the application of the proposed
      method, confirming that whole brain FCMs are not random matrices. On the other
      hand, several FCM submatrices did not significantly test out of randomness.
      COMPARISON WITH EXISTING METHODS: The proposed method does not replace graph
      theory measures; instead, it assesses a different aspect of functional
      connectivity. Features not included in graph theory are small numbers of nodes,
      testing submatrices of an FCM and handling negative as well as positive edge
      values. CONCLUSION: The random test not only determines randomness, but also
      serves as an indicator of smaller non-random patterns within a non-random FCM.
      Outcomes suggest that a lower order model may be sufficient as a broad
      description of the data, but it also indicates a loss of information. The
      developed randomness measure assesses a different aspect of randomness from that
      of graph theory.

PMID- 29601888
TI  - Reward sensitivity following boredom and cognitive effort: A high-powered
      neurophysiological investigation.
AB  - What do people feel like doing after they have exerted cognitive effort or are
      bored? Here, we empirically test whether people are drawn to rewards (at the
      neural level) following cognitive effort and boredom. This elucidates the
      experiences and consequences of engaging in cognitive effort, and compares it to
      the consequences of experiencing boredom, an affective state with predicted
      similar motivational consequences. Event-related potentials were recorded after
      participants (N = 243) were randomized into one of three conditions - boredom
      (passively observing strings of numbers), cognitive effort (adding 3 to each
      digit of a four-digit number), or control. In the subsequent task, we focused on
      the feedback negativity (FN) to assess the brain's immediate response to the
      presence or absence of reward. Phenomenologically, participants in the boredom
      condition reported more fatigue than those in the cognitive effort condition,
      despite reporting exerting less effort. Results suggest participants in the
      boredom condition exhibited larger FN amplitude than participants in the control
      condition, while the cognitive effort condition was neither different from
      boredom nor control. The neural and methodological implications for ego depletion
      research, including issues of replicability, are discussed.

PMID- 29601889
TI  - Sleep deprivation increases the costs of attentional effort: Performance,
      preference and pupil size.
AB  - Sleep deprivation (SD) consistently degrades performance in tasks requiring
      sustained attention, resulting in slower and more variable response times that
      worsen with time-on-task. Loss of motivation to exert effort may exacerbate
      performance degradation during SD. To test this, we evaluated sustained
      performance on a vigilance task, combining this with an effort-based decision
      making task and pupillometry. Vigilance was tested at rest and after sleep
      deprivation, under different incentive conditions (1, 5 or 15 cents for fast
      responses). Subsequently, preference measures were collected from an effort
      discounting task, in which a commensurate reward was offered for maintaining
      attentional performance for different durations (1, 5, 10, 20 or 30 min).
      Vigilance was impaired during SD, in a manner modulated by reward value.
      Preference metrics showed that the value of available rewards was discounted by
      task duration, an effect compounded by SD. Pupillometry revealed that arousal was
      modulated during SD in a value-based manner, and moment-to-moment fluctuations in
      pupil diameter were directly predictive of performance. Together, these data
      demonstrate that attentional performance can be interpreted within a value-based
      effort allocation framework, such that the perceived cost of attentional effort
      increases after sleep deprivation.

PMID- 29601890
TI  - The silencing of replication protein A1 induced cell apoptosis via regulating
      Caspase 3.
AB  - AIMS: Gastrointestinal cancers are a kind of deadly malignancy afflicting close
      to a million peoples worldwide. 5-Fluorouracil (5-Fu) is a main chemotherapeutic
      agent for cancer treatment. However, prolonged exposure of 5-Fu to cancer cells
      may cause chemoresistance and decrease the therapeutic potential of 5-Fu. MAIN
      METHODS: Replication protein A (RPA) is a component of the origin recognition
      complex. In our study, we explored the role of RPA1 in hepatocellular carcinoma
      cell SMMC-7721, gastric cancer cell SGC-7901 and colorectal cancer HT-29 via
      lentiviral particles infection. Flow cytometry assay was used to examine the
      effect of RPA1 on cell proliferation, cell cycle and apoptosis. Western blot was
      employed to determine the role of RPA1 on Caspase 3 expression. KEY FINDINGS:
      Immunohistochemstry results showed that RPA1 was highly expressed in colorectal
      cancer tissues. Only 5-Fu or the knockdown of RPA1 suppressed cell clone
      formation, induced cell cycle arrest at the G1 phase and promoted cell apoptosis
      by regulating the protein level of Caspase 3. And the combination of the
      application of 5-Fu and RPA1 silencing significantly enhanced the above effects.
      SIGNIFICANCE: RPA1 serves as an oncogene during gastrointestinal cancers
      progression. These studies reveal a new target for gastrointestinal cancers
      therapy, and the combination of 5-Fu and silencing of RPA1 provides a new
      attractive therapeutic measure for gastrointestinal cancers.

PMID- 29601891
TI  - Dehydroepiandrosterone supplementation is not beneficial in the late
      postmenopausal period in diet-induced obese rats.
AB  - AIMS: Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that is a
      precursor of sexual hormones. It is reduced during aging and is strongly
      associated with insulin resistance and obesity. There is evidence for beneficial
      effects of this steroid, in both human and animal models, during perimenopause.
      However, the impact of DHEA treatment during late postmenopause on glucose
      metabolism is not clearly documented. We tested the hypothesis that DHEA
      supplementation could improve insulin sensitivity in an ovariectomized obese rat
      model (OVX) that was fed a high-fat diet for 11 weeks. MAIN METHODS: Female
      Wistar rats at 8 weeks of age were OVX or SHAM-operated. Eight weeks after the
      surgery, the animals were randomly treated with vehicle or DHEA for 3 weeks. Food
      intake, metabolic parameters and insulin sensitivity were evaluated. KEY
      FINDINGS: Following the ovariectomy, increased body weight gain, adiposity index,
      and feeding efficiency were observed, despite there being no change in food and
      energy intake. The OVX rats also displayed glucose intolerance, insulin
      resistance, decreased insulin-induced IRS1/2 tyrosine phosphorylation in the
      skeletal muscle, and reduced serum VLDL-c and TAG levels. OVX rats treated with
      10 mg/kg DHEA (OVX + DHEA) exhibited estradiol (E2) serum levels similar to SHAM
      animals, with no change in uterus mass. DHEA treatment also resulted in an
      increase in energy intake. SIGNIFICANCE: Despite the positive effects of DHEA
      supplementation observed in menopausal women and ovariectomized rats, a potential
      negative effect on glucose metabolism and insulin action in the late
      postmenopausal condition in diet-induced obese OVX rats are reported.

PMID- 29601892
TI  - Susceptibility of Brazilian influenza A(H1N1)pdm09 viruses to neuraminidase
      inhibitors in the 2014-2016 seasons: Identification of strains bearing mutations
      associated with reduced inhibition profile.
AB  - Neuraminidase inhibitors (NAIs) are the main class of antivirals currently used
      for the treatment of influenza infections. As influenza viruses are constantly
      evolving, drug-resistance can emerge resulting in reduced effectiveness of
      treatment. This study evaluated the presence of molecular markers associated with
      NAI susceptibility in 724 influenza A(H1N1)pdm09 positive samples from Brazilian
      surveillance system from the 2014-2016 seasons, including 76 isolates tested for
      oseltamivir (OST) susceptibility and 23 isolates also tested for zanamivir,
      peramivir and laninamivir susceptibility. We identified the H275Y (n = 3) and
      I223K (n = 1) NA substitutions, associated with reduced inhibition (RI) by the
      NAIs. Noteworthy, no epidemiological links were identified among the patients
      infected with the mutant viruses. Phylogenetic analysis from NA and hemagglutinin
      genes showed that mutant viruses were not clustered. All mutant virus strains
      carried the permissive substitutions V241I and N369K, in addition to the N386K,
      which has been shown to destabilize the NA structure. Functional NA analysis of
      one virus containing the H275Y mutation confirmed its highly RI profile to OST
      and peramivir and demonstrated that it had decreased viral replication and NA
      thermostability compared to the wild type virus. The remaining tested isolates
      presented normal inhibition profile to the NAIs tested. In conclusion, the
      overall frequency of influenza A(H1N1)pdm09 viruses bearing mutations associated
      with NAI RI was 0.6%, similar to what has been observed in recent global studies.

PMID- 29601893
TI  - Ribavirin-related compounds exert in vitro inhibitory effects toward rabies
      virus.
AB  - Rabies remains an invariably fatal neurological disease despite the availability
      of a preventive vaccination and post-exposure prophylaxis that must be
      immediately administered to the exposed individual before symptom onset. There is
      no effective medication for treatment during the symptomatic phase. Ribavirin, a
      guanine nucleoside analog, is a potent inhibitor of rabies virus (RABV)
      replication in vitro but lacks clinical efficacy. Therefore, we attempted to
      identify potential ribavirin analogs with comparable or superior anti-RABV
      activity. Antiviral activity and cytotoxicity of the compounds were initially
      examined in human neuroblastoma cells. Among the tested compounds, two exhibited
      a 5- to 27-fold higher anti-RABV activity than ribavirin. Examination of the anti
      RABV mechanisms of action of the compounds using time-of-addition and minigenome
      assays revealed that they inhibited viral genome replication and transcription.
      Addition of exogenous guanosine to RABV-infected cells diminished the antiviral
      activity of the compounds, suggesting that they are involved in guanosine
      triphosphate (GTP) pool depletion by inhibiting inosine monophosphate
      dehydrogenase (IMPDH). Taken together, our findings underline the potency of
      nucleoside analogs as a class of antiviral compounds for the development of novel
      agents against RABV.

PMID- 29601894
TI  - Susceptibility of paramyxoviruses and filoviruses to inhibition by 2'-monofluoro-
      and 2'-difluoro-4'-azidocytidine analogs.
AB  - Ebolaviruses, marburgviruses, and henipaviruses are zoonotic pathogens belonging
      to the Filoviridae and Paramyxoviridae families. They exemplify viruses that
      continue to spill over into the human population, causing outbreaks characterized
      by high mortality and significant clinical sequelae in survivors of infection.
      There are currently no approved small molecule therapeutics for use in humans
      against these viruses. In this study, we evaluated the antiviral activity of the
      nucleoside analog 4'-azidocytidine (4'N3-C, R1479) and its 2'-monofluoro- and 2'
      difluoro-modified analogs (2'F-4'N3-C and 2'diF-4'N3-C) against representative
      paramyxoviruses (Nipah virus, Hendra virus, measles virus, and human
      parainfluenza virus 3) and filoviruses (Ebola virus, Sudan virus, and Ravn
      virus). We observed enhanced antiviral activity against paramyxoviruses with both
      2'diF-4'N3-C and 2'F-4'N3-C compared to R1479. On the other hand, while R1479 and
      2'diF-4'N3-C inhibited filoviruses similarly to paramyxoviruses, we observed 10
      fold lower filovirus inhibition by 2'F-4'N3-C. To our knowledge, this is the
      first study to compare the susceptibility of paramyxoviruses and filoviruses to
      R1479 and its 2'-fluoro-modified analogs. The activity of these compounds against
      negative-strand RNA viruses endorses the development of 4'-modified nucleoside
      analogs as broad-spectrum therapeutics against zoonotic viruses of public health
      importance.

PMID- 29601896
TI  - Differentiating between bipolar and unipolar depression in functional and
      structural MRI studies.
AB  - Distinguishing depression in bipolar disorder (BD) from unipolar depression (UD)
      solely based on clinical clues is difficult, which has led to the exploration of
      promising neural markers in neuroimaging measures for discriminating between BD
      depression and UD. In this article, we review structural and functional magnetic
      resonance imaging (MRI) studies that directly compare UD and BD depression based
      on neuroimaging modalities including functional MRI studies on regional brain
      activation or functional connectivity, structural MRI on gray or white matter
      morphology, and pattern classification analyses using a machine learning
      approach. Numerous studies have reported distinct functional and structural
      alterations in emotion- or reward-processing neural circuits between BD
      depression and UD. Different activation patterns in neural networks including the
      amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC), and striatum
      during emotion-, reward-, or cognition-related tasks have been reported between
      BD and UD. A stronger functional connectivity pattern in BD was pronounced in
      default mode and in frontoparietal networks and brain regions including the PFC,
      ACC, parietal and temporal regions, and thalamus compared to UD. Gray matter
      volume differences in the ACC, hippocampus, amygdala, and dorsolateral prefrontal
      cortex (DLPFC) have been reported between BD and UD, along with a thinner DLPFC
      in BD compared to UD. BD showed reduced integrity in the anterior part of the
      corpus callosum and posterior cingulum compared to UD. Several studies performed
      pattern classification analysis using structural and functional MRI data to
      distinguish between UD and BD depression using a supervised machine learning
      approach, which yielded a moderate level of accuracy in classification.

PMID- 29601895
TI  - Chronic administration of amphetamines disturbs development of neural progenitor
      cells in young adult nonhuman primates.
AB  - The detrimental effects of amphetamines on developmental stages of NPCs are
      limited to rodent brain and it is not known if these effects occur in nonhuman
      primates which are the focus of the current investigation. Young adult rhesus
      macaques either experienced MDMA only, a combination of amphetamines (MDMA, MDA
      and methamphetamine) or no amphetamines (controls) and hippocampal tissue was
      processed for immunohistochemical analysis.Quantitative stereological analysis
      showed that intermittent exposure to MDMA or the three amphetamines over 9.6
      months causes >80% decrease in the number of Ki-67 cells (actively dividing NPCs)
      and >50% decrease in the number of NeuroD1 cells (NPCs that have attained a
      neuronal phenotype). Co-labeling analysis revealed distinct, actively dividing
      hippocampal NPCs in the subgranular zone of the dentate gyrus that were in
      transition from stem-like radial glia-like cells (type-1) to immature transiently
      amplifying neuroblasts (type-2a, type-2b, and type-3).MDMA-alone and the
      combination reduced the number of dividing type-1 and type-3 NPCs and cells that
      were not NPCs. These data indicate that amphetamines interfere with the division
      and migration of NPCs. Notably, the reduction in the number of NPCs and immature
      neurons were not associated with changes in cell death (via apoptosis) or granule
      cell neuron numbers, indicating that amphetamines selectively affected the
      generation and maturation of newly born granule cell neurons. In sum, our
      findings suggest that alterations in the cellular composition in the dentate
      gyrus during chronic exposure to amphetamines can effect neuroplasticity in the
      hippocampus and influence functional properties of hippocampal neurons.

PMID- 29601897
TI  - Does Pain Affect Preference? The Effect of Tonic Laboratory Pain on Discounting
      of Delayed Rewards.
AB  - : Chronic pain patients show elevated risk behavior on decision-making tasks, as
      well as increased health risk behaviors (eg, smoking, prescription opioid abuse).
      Determining pain's effect on underlying cognitive processes that are associated
      with risk behavior is confounded by comorbidities linked with chronic pain,
      including depression, anxiety, and substance abuse. Therefore, to understand
      pain's effect on delay discounting, a behavioral process assessing the extent to
      which outcomes are devalued as a function of their delay, the present study
      evaluated the effect of laboratory pain on delay discounting in healthy young
      adults (N = 85). Using a mixed factorial design, pain (topical capsaicin and
      warmth) as well as active control (warmth) groups completed a delay discounting
      task before and during exposure to their respective manipulations. Whereas the
      pain condition had no effect on delay discounting, participants' pain intensity,
      unpleasantness, and pain-induced negative valence were associated with less
      discounting of delayed rewards. However, the effects were very small.
      PERSPECTIVE: The results suggest that experimental pain may not increase delay
      discounting, rather sensitivity to pain predicts a very small decrease in
      discounting of delayed rewards. Although the results are limited to healthy
      volunteers, this experimental approach allows us to examine the relationship
      between pain and delay discounting in a controlled manner. Better understanding
      of pain-related decision-making may lead to improved treatment of health risk
      behaviors for individuals experiencing pain.

PMID- 29601898
TI  - Qualitative and Quantitative Aspects of Pain in Patients With Myotonic Dystrophy
      Type 2.
AB  - : Pain is a common but often ignored symptom in patients with myotonic dystrophy
      type 2 (DM2). In this explorative study, we assessed qualitative and quantitative
      aspects of pain in DM2 using 4 questionnaires and quantitative sensory testing. A
      disease control group (fibromyalgia [FMS]) as well as healthy controls were used
      to compare the results, because pain in DM2 shows many clinical similarities to
      pain in FMS. Thirty-four patients with genetically confirmed DM2 (71% female,
      mean age 54 years), 28 patients with FMS, and 33 healthy controls were included,
      age- as well as sex-matched. Pain prevalence was 65% in DM2, 100% in FMS (P <
      .001), and 15% in healthy controls (P < .001). The mean of the pressure pain
      thresholds was lower in DM2 than in healthy controls (P = .016), with the largest
      differences in the rectus femoris, trapezius, and thenar muscles. Mechanical and
      electric pain thresholds were significantly higher in DM2 than in FMS, and no
      differences were found in electric pain thresholds between DM2 and healthy
      controls. These results confirm that pain is a frequent and important symptom in
      patients with DM2, affecting quality of life. Peripheral mechanisms of pain seem
      to play a role in DM2. The widespreadness of the hyperalgesia suggests central
      sensitization, but this finding was not supported by the other results. This
      study opens new avenues for further research and eventually novel treatment
      strategies, in DM2 as well as in other muscular disorders. PERSPECTIVE: This
      article presents qualitative as well as quantitative aspects of pain in patients
      with DM2. Pain is a frequent and important symptom in patients with DM2,
      affecting quality of life. We found mechanical hyperalgesia, indicative of a
      peripheral mechanism of pain. The widespreadness of hyperalgesia may suggest
      central sensitization, but this finding was not supported by other results and
      needs further exploration.

PMID- 29601899
TI  - Longitudinal changes in bone parameters in young girls with anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa (AN) during childhood and adolescence has been
      reported to adversely affect bone health, but few studies have investigated
      longitudinal changes. METHOD: DXA-derived bone parameters and body composition
      were retrospectively assessed in 111 young girls with AN with a median age of
      15.4 years (10.9, 19.8). In 68 (61%) vertebral fracture assessment (VFA) was
      performed and in 31 (28%), a follow-up DXA was performed. Correlations with
      growth, changes in body composition and effects of illness duration and
      menstruation were examined. Size adjusted DXA standard deviation scores were
      calculated for total body (TB) less head bone mineral content (TBLH-BMC) and
      lumbar spine bone mineral apparent density (LS-BMAD). RESULTS: Mean (range) bone
      area (BA) for height centile was 27.1 (0-97), and mean lean mass for height
      centile was 28.8 (0-95) at baseline. Mean (range) LS BMAD was -1.0 (-2.6, 0.8)
      SDS at first and - 1.2 (-3.0, -0.2) at second DXA (p = 0.023). On follow up, lean
      mass for height increased from 27th centile (0, 75) to 40th centile (0, 70) (p =
      0.006), and fat mass for height increased from 55 g/cm to 67 g/cm (11.3, 124.2)
      (p < 0.001). Duration of illness was the only negative predictor of LS BMAD (p <
      0.0001). Change in height SDS was the only positive predictor of change in TBLH
      BMC (r = 0.384, p = 0.037), and change in LS BMAD (r-0.934, p < 0.0001). Of 68
      patients who had VFA, 4 (5.9%) had a mild vertebral fracture. CONCLUSION: Bones
      are smaller and less dense in childhood/adolescent AN compared to healthy
      adolescents. Although there are significant gains in lean mass and fat mass, over
      time, BMAD SDS decreases slightly. Improvement in BMAD SDS is related to
      improvement in height SDS.

PMID- 29601900
TI  - Neonatal hyperinsulinemic hypoglycemia in a patient with 9p deletion syndrome.
AB  - We report the clinical and neuroradiological findings in a young boy harboring
      the 9p deletion syndrome including the novel findings of thalamic infarction and
      germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the
      hypoglycemic events and the ventriculomegaly found in this patient have
      previously only been reported in two patients, while the thalamic infarction and
      germinal matrix haemorrhage are novel features.

PMID- 29601902
TI  - Rethinking What We Know About Hemorrhoids.
AB  - Although hemorrhoids are responsible for considerable economic cost and personal
      suffering, they have received surprisingly little research attention. In the
      United States, hemorrhoids are the third most common outpatient gastrointestinal
      diagnosis with nearly 4 million office and emergency department visits annually.
      The etiology of hemorrhoids is speculative. A low-fiber diet and constipation
      have historically been thought to increase the risk for hemorrhoids, but not
      proven. Symptoms commonly attributed to hemorrhoids include bleeding, pain,
      pruritus, fecal seepage, prolapse, and mucus discharge. Research has found that
      these symptoms were equally reported by patients with and without hemorrhoids.
      Medical therapies for hemorrhoids have not been formally studied except for fiber
      where the results have been inconsistent. A number of office-based interventions
      such as rubber band ligation and infrared coagulation are widely used and
      economically favorable for practitioners. Surgical procedures are effective at
      eliminating hemorrhoids but may be painful. Given the burden of disease and
      numerous gaps in our understanding, the time has come for targeted research to
      understand the cause, symptoms, and best treatment for patients with symptomatic
      hemorrhoids.

PMID- 29601901
TI  - 3D-printing porosity: A new approach to creating elevated porosity materials and
      structures.
AB  - : We introduce a new process that enables the ability to 3D-print high porosity
      materials and structures by combining the newly introduced 3D-Painting process
      with traditional salt-leaching. The synthesis and resulting properties of three
      3D-printable inks comprised of varying volume ratios (25:75, 50:50, 70:30) of
      CuSO4 salt and polylactide-co-glycolide (PLGA), as well as their as-printed and
      salt-leached counterparts, are discussed. The resulting materials are comprised
      entirely of PLGA (F-PLGA), but exhibit porosities proportional to the original
      CuSO4 content. The three distinct F-PLGA materials exhibit average porosities of
      66.6-94.4%, elastic moduli of 112.6-2.7 MPa, and absorbency of 195.7-742.2%.
      Studies with adult human mesenchymal stem cells (hMSCs) demonstrated that
      elevated porosity substantially promotes cell adhesion, viability, and
      proliferation. F-PLGA can also act as carriers for weak, naturally or
      synthetically-derived hydrogels. Finally, we show that this process can be
      extended to other materials including graphene, metals, and ceramics. STATEMENT
      OF SIGNIFICANCE: Porosity plays an essential role in the performance and function
      of biomaterials, tissue engineering, and clinical medicine. For the same material
      chemistry, the level of porosity can dictate if it is cell, tissue, or organ
      friendly; with low porosity materials being far less favorable than high porosity
      materials. Despite its importance, it has been difficult to create three
      dimensionally printed structures that are comprised of materials that have
      extremely high levels of internal porosity yet are surgically friendly (able to
      handle and utilize during surgical operations). In this work, we extend a new
      materials-centric approach to 3D-printing, 3D-Painting, to 3D-printing structures
      made almost entirely out of water-soluble salt. The structures are then washed in
      a specific way that not only extracts the salt but causes the structures to
      increase in size. With the salt removed, the resulting medical polymer structures
      are almost entirely porous and contain very little solid material, but the
      maintain their 3D-printed form and are highly compatible with adult human stem
      cells, are mechanically robust enough to use in surgical manipulations, and can
      be filled with and act as carriers for biologically active liquids and gels. We
      can also extend this process to three-dimensionally printing other porous
      materials, such as graphene, metals, and even ceramics.

PMID- 29601903
TI  - Endoscopic Drainage of Pancreatic Fluid Collections.
AB  - Endoscopy has emerged as a mainstay in the management of pancreatic fluid
      collections (PFCs), representing an important advance in clinical medicine that
      has significantly improved the risk-benefit ratio of treating this complex
      patient population. While endoscopic pseudocyst drainage has generally supplanted
      surgical and percutaneous approaches, the optimal strategy for walled-off
      necrosis remains variable and multi-disciplinary despite an emerging trend from
      randomized trials favoring endoscopy. Although several issues pertaining to
      endoscopic drainage appear to have been settled - such as the use of endoscopic
      ultrasound - other pressing questions - including the optimal prosthesis and
      debridement strategy - remain unanswered, and rigorous investigation is needed.
      This review aims to provide an evidence-based but practical appraisal of the
      endoscopic drainage of PFCs through the perspective of the author, with an
      emphasis on relevant clinical and endoscopic considerations and important
      research questions.

PMID- 29601904
TI  - Protoporphyrin IX formation after application of methyl aminolevulinate on the
      face and scalp with and without prior curettage.
AB  - BACKGROUND: Pulse photodynamic therapy (PDT) is carried out as classical PDT
      except that methyl aminolaevulinate (MAL) is removed after 30 min. Protoporphyrin
      IX (PpIX) accumulation becomes lower after 3 h in pulse-PDT than in classical
      PDT, but pulse-PDT still has full treatment effect on actinic keratosis (AK). The
      present study aimed to investigate when PpIX formation in classical PDT without
      curettage reaches the PpIX level in pulse-PDT with curettage in the skin of the
      face and scalp. METHODS: Fourteen patients with AKs in the face and scalp were
      included in this pilot study. Each patient had two fields randomly allocated to
      two different regimes: (i) continuing MAL incubation without prior curettage (
      Cur) and (ii) 30 min MAL incubation after curettage (+Cur). The PpIX level in
      each field was measured with a hand-held fluorescence photometer every 30 min for
      6 h after MAL application. No illumination was performed. RESULTS: The median
      PpIX level in the +Cur field after 3 h was 22 arbitrary units (AU), which
      represents the amount of PpIX that could have been photobleached after pulse-PDT
      with maximal treatment effect. After 3 h the median PpIX level in the -Cur field
      was 20 AU, which was not significantly different from the level in the +Cur field
      (p = 0.9). CONCLUSIONS: We propose PDT without curettage as follows: 3 h of MAL
      incubation and subsequently sufficient illumination. The treatment effect of this
      regime should be tested to verify if curettage of the face and scalp area may be
      omitted in PDT.

PMID- 29601906
TI  - Melatonin therapy for diabetic cardiomyopathy: A mechanism involving Syk
      mitochondrial complex I-SERCA pathway.
AB  - Melatonin and its metabolites have been demonstrated to modulate the glucose,
      dyslipidemia and other metabolic disorders. This study aimed to explore a novel
      mechanism responsible for diabetic cardiomyopathy development, and also validated
      whether melatonin played a protective role in repairing damaged heart in the
      diabetes setting. Our data demonstrated that spleen tyrosine kinase (Syk) was
      activated by chronic high-glucose stimulus and contributed to the development of
      diabetic cardiomyopathy. However, genetic ablation of Syk or supplementation of
      melatonin to inhibit Syk activation improved diabetic myocardial function,
      reduced cardiac fibrosis and preserved cardiomyocytes viability. Mechanistically,
      activated Syk repressed the expression and activity of mitochondrial complex I
      (COX-1), unfortunately evoking mitochondrial and/or cellular ROS overproduction.
      Subsequently, excessive superoxide facilitated SERCA peroxidation which failed to
      re-uptake the cytoplasmic calcium back into endoplasmic reticulum (ER), leading
      to cellular calcium overload. Finally, activated oxidative stress and calcium
      overload collectively promoted the high-glucose-induced cardiomyocytes death via
      caspase-9-related mitochondrial apoptosis and caspase-12-involved ER apoptosis,
      respectively. Interestingly, inhibition of Syk via Syk genetic ablation or
      melatonin administration blocked Syk/COX-1/SERCA signalling pathways, and thus
      abolished mitochondrial- and ER-mediated cardiomyocyte death in the setting of
      diabetes. Based on these results, we suggest a novel pathway by which high
      glucose stimulus induces diabetic cardiomyopathy is possibly through an
      activation of Syk/COX-1/SERCA axis which could be abrogated by melatonin
      treatment.

PMID- 29601905
TI  - Theranostic-PDT with the antibody anti isoform 4 SOD mitocondrial labeled with
      PpIX in the lung cancer cell line A-549.
AB  - BACKGROUND: In this work, a drug product composed of an IgM antibody derived from
      a hybridoma subclone 4C1F6D5G7B8 was prepared and further labeled with PpIX to be
      used in cell lines A-549 and MRC-5. The aim of this work was to evaluate the
      potential theranostic activity of the obtained product together with photodynamic
      therapy (PDT). METHODS: The IgM antibody labeled with PpIX was used in different
      concentrations to perform theranostics with PDT in cell lines A-549 and MRC-5 in
      order to identify the specificity of IgM antibody in lung cancer cells by means
      of a LED-irradiation system set at 630 nm. The location of the conjugate was
      further determined by confocal microscopy. RESULTS: The theranostic with
      conjugate Ab-PpIX in the A-549 cell lines showed fluorescence by confocal
      microscopy, whereas the MRC-5 cell line showed no reactivity. The PDT with the
      conjugate in the cell line A-549 decreased its viability 70% compared to the
      control. On the contrary, with the MRC-5 cell line no viability diference was
      shown. The confocal microscopy applied to the cell line A-549 showed that the Ab
      PpIX was majorly located at the cytoplasm. CONCLUSION: Ab-PpIX showed
      therapeutical potential in lung cancer cells A-549 and had no activity in non
      cancerous lung cells (MCR-5).

PMID- 29601907
TI  - Inhibition of DNMT suppresses the stemness of colorectal cancer cells through
      down-regulating Wnt signaling pathway.
AB  - Cancer stem cell (CSC) theory reveals a new insight into the understanding of
      tumorigenesis and metastasis. Recently, DNA methylation is suggested to be a
      potential epigenetic mechanism for maintenance of CSCs. What's more, studies have
      shown that DNA methyltransferase (DNMT) is essential for CSCs and deletion of
      DNMT can reduce tumorigenesis by limiting CSC pool. Therefore, targeting the
      epigenetic modifiers especially DNA methylation offers an optional strategy for
      treating human cancers. In the present study we found that DNMT inhibitor 5-Aza
      2'-deoxycytidine (5-AzaDC) markedly reduced colorectal CSC abundance in vitro and
      suppressed liver metastatic tumor growth in vivo. And 5-AzaDC inhibited the
      expression of active beta-catenin and down-regulated the Wnt signaling pathway.
      The Wnt inhibitors were frequently inactivated by promoter methylation in
      colorectal cancer; however analysis of TCGA data base showed that only the
      expression of SFRP1 was significantly reduced in tumors compared to normal
      tissues. In addition, restoring of SFRP1 expression inhibited the stem cell-like
      potential of colorectal cancer cells. Our results indicated that inhibition of
      DNMT blocked the self-renewal of colorectal CSCs and SFRP1 was essential for the
      maintenance of colorectal CSCs.

PMID- 29601908
TI  - Outcomes of Patients Undergoing Surgical Management of Multiple Ventricular
      Septal Defects.
AB  - Surgical treatment of multiple ventricular septal defects (VSDs) has advanced
      significantly in recent years, yet remains technically challenging. With high
      rates of complications and reoperations, we sought to assess the outcomes of
      patients undergoing a variety of management techniques for multiple VSDs. From
      1988 to 2015, 157 consecutive patients underwent surgical management of multiple
      VSDs at a median age of 2.2 months (2 days-16 years). Sixty-nine patients (44%)
      had exclusively multiple VSDs, 62 patients (39%) had multiple VSDs with
      concomitant intracardiac anomalies, and 26 patients (17%) had multiple VSDs with
      aortic arch anomalies. The predominant techniques used at the initial operations
      were patch closure (84 patients), pulmonary artery band (83 patients), suture
      closure (37 patients), and sandwich technique (13 patients). Eighteen patients
      underwent ventriculotomies. There were 3 hospital deaths (2%). Mean follow-up
      time was 8.6 +/- 6 years (1 day-22 years). Four patients died during follow-up,
      whereas freedom from reoperations was 52% (95% confidence interval 42%-61%) at 16
      years. Freedom from reoperation was significantly lower in the 1988-2002 era than
      in the post-2002 era (38% vs 73%, P = 0.016). Pacemaker implantation was
      ultimately required in 9% (14 of 150) of patients. No deleterious impact of a
      ventriculotomy could be detected. Surgical treatment of multiple VSDs can be
      performed with excellent short- and long-term survival, and normal late
      functional outcome, however, carries a significant rate of reoperation. The
      recent inclusion of absorbable pulmonary artery bands and the sandwich technique
      appear safe and are useful adjuncts in these patients.

PMID- 29601909
TI  - Pseudoaneurysm Formation Associated With a Modified Blalock-Taussig Shunt.

PMID- 29601910
TI  - Safety assessment of vitacoxib: 180-day chronic oral toxicity studies.
AB  - Vitacoxib, a selective COX-2 inhibitor, is approved for the relief of pain and
      inflammation associated with orthopedic surgery and osteoarthritis in dogs. In
      the current study, a chronic toxicity research was performed to evaluate the
      safety of vitacoxib in male and female rats for long-term. Vitacoxib was dosed
      orally to groups of rats for 180 days at 1.2, 6, 30 mg/kg bw/day by gavage. The
      chronic study oral administration of vitacoxib did not show observational or
      toxicological effects on the body or organ weights, food consumption, hematology
      and biochemistry at dose 6 mg/kg bw. However, vitacoxib (30 mg/kg) showed minor
      alterations to histopathology of liver, kidney and stomach related to treatment.
      These results provide further indication that vitacoxib is safe and well
      tolerated in rats after 180 days of daily oral administration at 6 mg/kg bw and
      the NOAEL for both sexes was 6 mg/kg bw for 180 consecutive days.

PMID- 29601911
TI  - Neuroprotective effect of the carnosine - alpha-lipoic acid nanomicellar complex
      in a model of early-stage Parkinson's disease.
AB  - In a model of early-stage Parkinson's disease induced by a single intranasal
      administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Wistar
      rats, a neuroprotective effect of a new derivative of carnosine and alpha-lipoic
      acid (C/LA nanomicellar complex) was demonstrated. Acute intraperitoneal
      administration of carnosine, alpha-lipoic acid and C/LA complex following MPTP
      administration normalized the total antioxidant activity in the brain tissue. Of
      all the compounds tested only C/LA complex normalized the metabolism of dopamine
      (DA) and serotonin (5-HT), while its components did not show similar effects when
      used separately. C/LA complex effectively restored the level of DA metabolites:
      the level of DOPAC was increased by 24.7 +/- 5.6% compared to the animals that
      had received MPTP only, and the level of HVA was restored to the values observed
      in the intact animals. Integral metabolic indices of DA (DOPAC/DA and HVA/DA
      ratios) and 5-HT turnover (5-HIAA/5-HT ratio) in the striatum tended to increase
      in case of C/LA complex administration.

PMID- 29601912
TI  - Residue behavior and dietary intake risk assessment of carbosulfan and its
      metabolites in cucumber.
AB  - The residue behavior and dietary intake risks of carbosulfan and its metabolites
      in cucumbers were investigated. A quick and reliable method for determining
      carbosulfan and its metabolite residues in cucumbers was established using
      ultrahigh performance liquid chromatography-tandem mass spectrometry. The
      fortified recoveries ranged from 87.2% to 91.0% with relative standard deviations
      of 3.2%-8.1%. The dissipation results showed that carbosulfan was transformed
      into carbofuran and 3-hydroxy carbofuran in cucumbers. The half-life of
      carbosulfan was 1.5 days, and the half-life of carbofuran was 45 days. The final
      residues of carbosulfan varied from 0.245 to 0.005 mg/kg and carbofuran varied
      from 0.123 to 0.008 mg/kg. After a 5-day application period the residues of
      carbosulfan was 0.113 mg/kg that was below the maximum residue limit set by China
      (0.2 mg/kg), and the residues of carbofuran was 0.055 mg/kg that was higher than
      the maximum residue limit set by China (0.02 mg/kg). The risk assessment results
      indicated that the dietary intake risks of carbosulfan and carbofuran from
      cucumber consumption were safe for Chinese consumers, but pre-harvest intervals
      should be strictly recommended for 7 days at the recommended dose to ensure that
      food quality conforms to the MRL standard. This study provides a method and data
      for scientifically evaluating dietary intake risks of carbosulfan and its more
      toxic metabolites.

PMID- 29601913
TI  - Fasting serum amino acids concentration is associated with insulin resistance and
      pro-inflammatory cytokines.
AB  - AIMS: We evaluated specific alterations in amino acids (AAs) profile in patients
      with type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) compared
      with healthy controls. In addition, we tried to find the mechanisms behind these
      AA alterations. METHODS: Twenty AAs, TNF-alpha, and IL-6 were analyzed in fasting
      serum samples from a total of 198 individuals (56 drug-naive patients with T2DM,
      69 patients IFG, and 73 healthy controls). The C2C12 mouse myoblast cell lines
      were used to examine the changes of MAFbx and MuRF1 expressions, which are muscle
      specific E3 ligases acting as major mediators of skeletal muscle proteolysis,
      after development of insulin resistance induced by palmitate treatment. RESULTS:
      In addition to branched chain amino acids BCAAs, fasting serum AAs such as
      glutamic acid, lysine, phenylalanine, arginine, alanine, tyrosine, aspartic acid,
      were higher in patients with T2DM and intermediately elevated in patients with
      IFG compared with normoglycemic controls. These serum AA concentrations
      positively correlated with fasting glucose, homeostasis model assessment of
      insulin resistance (HOMA-IR), and pro-inflammatory cytokines. In addition, HOMA
      IR and pro-inflammatory cytokines were two important independent predictors of
      serum AA levels. In vitro experiments showed that palmitate treatment in C2C12
      myotubes induced insulin resistance, increased pro-inflammatory cytokine gene
      expression, and increased MAFbx gene and protein expression. CONCLUSIONS: The
      increase in fasting serum AAs can be an early manifestation of insulin
      resistance. Increased muscle proteolysis induced by insulin resistance and
      inflammatory cytokines can be a possible mechanism for the rise in serum AA
      levels.

PMID- 29601914
TI  - The association between pre-pregnancy impaired fasting glucose and adverse
      perinatal outcome.
AB  - AIMS: To evaluate the association between impaired fasting glucose (IFG) prior to
      pregnancy with maternal and neonatal outcome. METHODS: A retrospective cohort
      study of singleton deliveries in a single, tertiary, university-affiliated
      medical center between August 2007 and December 2012. We included women who had a
      fasting glucose test done up to 26 weeks prior to pregnancy. We excluded women
      with diabetes mellitus and women carrying a fetus with structural or chromosomal
      anomalies. Maternal and neonatal outcome were compared between two groups: women
      with pre-pregnancy IFG (defined as fasting glucose >=100 mg/dl and <126 mg/dl)
      versus those with normoglycemia (fasting glucose <100 mg/dl). RESULTS: Overall,
      1945 women met inclusion criteria. Of whom, 1790 had pre-pregnancy glucose <100
      mg/dl and 155 had IFG. There were no differences between groups in basic
      characteristics. As for maternal outcome, IFG was associated with higher rates of
      mild preeclampsia (5.16% vs. 0.67%), abnormal glucose challenge test (21.94% vs.
      13.46%) and gestational diabetes (13.55 vs. 2.85%), p < 0.05 for all. There were
      no significant differences in neonatal outcome. After adjusting for potential
      confounders, on multivariable logistic regression, pre-pregnancy IFG remained
      significantly and independently associated with mild preeclampsia (aOR 6.92, 95%
      CI 2.68-18.05, p < 0.001). CONCLUSIONS: Pre-pregnancy IFG is associated with
      increased risk for abnormal glucose challenge test and gestational diabetes, and
      it is an independent risk factor for adverse pregnancy outcome including mild
      preeclampsia.

PMID- 29601915
TI  - Effect of the economic crisis on the use of health and home care services among
      elderly Spanish diabetes patients.
AB  - AIMS: To describe the utilization of health and home care services among older
      people (>=65 years) with diabetes during the economic crisis; to identify the
      factors associated with changes in the utilization of these services; and to
      study the time trends (2009-2014). METHODS: We used the European Health Interview
      Surveys for Spain (EEHSS) for 2009/10 and 2014. The dependent variables included
      self-reported hospitalizations; general practitioner (GP) visits; 'other
      healthcare services' (OHS) used; and home care services (HCS) used. RESULTS: We
      identified 6026 and 6020 diabetic patients (EEHSS2009 and EEHSS2014,
      respectively). A significant decrease in the number of GP visits (OR 0.94; 95% CI
      0.91-0.98) and the use of HCS (OR 0.95; 95% CI 0.91-0.99) was found; however, we
      found an increase in the use of OHS (OR 1.06; 95% CI 1.02-1.10). Multivariate
      models showed that factors associated with an increased use included chronic
      conditions, worse self-rated health, pain and mental disorders. Physical activity
      was a strong predictor of lower hospitalizations and HCS use. Female gender was
      associated with significantly lower hospitalizations and a higher use of OHC and
      HCS. CONCLUSION: We found a decrease in the number of GP visits and the use of
      HCS among elderly diabetic adults; however, we also observed an increase in the
      use of OHS, which may partly explain this decrease in the figures. Significant
      differences in the use of health services were found according to gender. The
      effect of the economic crisis, if any, seems to have had a small magnitude.

PMID- 29601916
TI  - B-RCA revealed circulating miR-33a/b associates with serum cholesterol in type 2
      diabetes patients at high risk of ASCVD.
AB  - AIMS: Type 2 diabetes (T2D) is a complex metabolic disease with high incidence
      throughout the world. Dyslipidemia is the leading cause of atherosclerotic
      cardiovascular diseases (ASCVD) in T2D patients. hsa-miR-33 (miR-33) serves as a
      regulator in lipid metabolism. We hypothesized that blood miR-33 associates with
      serum lipids in T2D patients at high risk of ASCVD events. METHODS: We developed
      a branched rolling circle amplification (B-RCA) method and assessed its
      sensitivity and specificity with miR-33a/b standards by traditional TaqMan assay.
      Circulating miR-33a/b level was then determined with B-RCA in 30 T2D patients at
      high risk for developing ASCVD and 33 healthy controls. Pearson correlation
      coefficient was used to evaluate the correlation between circulating miR-33a/b
      and serum cholesterol. RESULTS: Compared with TaqMan assay, B-RCA method showed a
      similar specificity and a 100-fold higher sensitivity for miR-33a detection.
      Circulating miR-33a/b level is positively correlated with serum total cholesterol
      (TC) (r = 0.364, p = 0.048) and low-density lipoprotein cholesterol (LDL-C) (r =
      0.383, p = 0.037) in T2D patients at high risk for developing ASCVD. CONCLUSIONS:
      Our B-RCA method provided an alternative strategy with specificity and high
      sensitivity for circulating miRNAs detection, and the results demonstrated that
      miR-33a/b might play an important role in cholesterol regulation.

PMID- 29601917
TI  - Measuring feeding difficulties in toddlers with Down syndrome.
AB  - Early feeding problems occur frequently across the population, but have a higher
      incidence in children with Down syndrome (DS). Early identification can possibly
      be improved with the help of a valid screening instrument based on caregiver
      reports. In a previous study, we investigated the concurrent validity of the
      Dutch version of the Montreal Children's Hospital Feeding Scale (MCH-FS, SEP in
      Dutch) in a sample of typically developing toddlers, and we found a correlation
      between the score on the instrument and observed behavior during a regular meal.
      The current pilot study was a replication in a sample of children with DS (aged
      1; 0-3; 0) and their primary caregivers (n = 32). The results showed that
      children in the sample did not score higher on the SEP than children in their
      respective norm groups. In addition, when caregivers reported more symptoms of
      feeding problems on the SEP, children showed more food refusal and negative
      affect during the observed meal. This suggests that the screening instrument is
      particularly associated with negative mealtime interactions. This is in contrast
      with earlier results, which mainly indicated a relation with eating skills.

PMID- 29601918
TI  - Effects of left dlPFC modulation on social cognitive processes following food
      sampling.
AB  - BACKGROUND: The dorsolateral prefrontal cortex (dlPFC) plays a central role in
      the inhibition of eating, but also the modulation of conscious thought processes
      that might precede, accompany or follow initial food tasting. The latter might be
      particularly important to the extent that post-tasting cognitions may drive
      prolonged eating beyond the satiety point. However, we know very little about the
      effect of the dlPFC on conation following initial food sampling. This
      investigation compared the effects of dlPFC attenuation using repetitive
      transcranial magnetic stimulation (rTMS) on social cognition following (Study 1)
      and prior to (Study 2) a food consumption opportunity. METHODS: In Study 1,
      participants (N = 21; Mage = 21 years) were randomized to active or sham
      continuous theta-burst stimulation (cTBS; an inhibitory variant of rTMS)
      targeting the left dlPFC followed by an interference task. Participants
      subsequently completed measures of attitudes, norms and perceived control
      following a mock taste test. In Study 2, a second sample of right handed
      participants (N = 37; Mage = 21 years) were assigned to active or sham cTBS,
      followed by an interference task and two measures of attitudes (implicit and
      explicit), both assessed prior to the same taste test paradigm. RESULTS: In Study
      1, findings revealed a reliable effect of cTBS on post-tasting attitudes (t(1,19)
      = 3.055, p = .007; d = 1.34), such that attitudes towards calorie dense snack
      foods were significantly more positive following active stimulation than
      following sham stimulation. Similar effects were found for social norms (t(1,19)
      = 3.024, p = .007, d = 1.31) and perceived control (t(1,20) = 19.247, p < .001, d
      = 0.50). In Study 2, no effects of cTBS were observed on pre-consumption
      attitudes, despite reliable effects on interference scores and subsequent
      consumption. CONCLUSIONS: The left dlPFC may selectively modulate facilitative
      social cognition following initial food sampling (but not pre-consumption).

PMID- 29601919
TI  - Parent-child health- and weight-focused conversations: Who is saying what and to
      whom?
AB  - The purpose of this study was to examine the prevalence of health-focused
      (healthy eating, physical activity) and weight-focused (weight, dieting) parent
      child conversations, and to understand who is talking and who is listening, by
      exploring the associations these conversations have with parent and child
      characteristics. The study population included 546 parents (age 27-36 years) who
      participated in Project EAT (Eating and Activity in Teens and Young Adults)-IV
      (2015-2016) and had a child aged 2-17 years. Cross-sectional prevalence ratios
      were calculated to identify associations between parent and child characteristics
      and the parent-child conversations. Conversations about healthy eating (82%) and
      physical activity (75%) were more prevalent than those about the child's weight
      (30%), and dieting (25%). In adjusted models, parents meeting physical activity
      recommendations had a higher prevalence of health-focused conversations (healthy
      eating PR = 1.10, 95% CI = 1.01, 1.20; physical activity PR = 1.12, 95% CI =
      1.02, 1.24); whereas, weight-focused conversations were more common among parents
      who had recently dieted and perceived their child to be overweight. Health
      focused and weight-focused conversations were highly common among the oldest
      children aged 9-17 years (health-focused = 90-93% and weight-focused = 42-53%);
      though, a substantial prevalence of health- and weight-focused conversations
      (>50% and >=10%, respectively) also occurred with the youngest children (2-4
      years). Findings suggest that parent-child health- and weight-focused
      conversations are common and that characteristics, including child's age and
      parents' physical activity, dieting, and perceptions of child weight, may be
      useful to consider in public health messaging, interventions, and family
      education that address parent-child communication.

PMID- 29601921
TI  - The family child care home environment and children's diet quality.
AB  - BACKGROUND: Developing healthy eating behaviors and food preferences in early
      childhood may help establish future healthy diets. Large numbers of children
      spend time in child care, but little research has assessed the nutritional
      quality of meals and snacks in family child care homes. Therefore, it is
      important to assess foods and beverages provided, policies related to nutrition
      and feeding children, and interactions between providers and children during
      mealtimes. We examined associations between the nutrition environments of family
      child care homes and children's diet quality. METHODS: We assessed the nutrition
      environments of 166 family child care homes using the Environment and Policy
      Assessment and Observation (EPAO) (scores range: 0-21). We also recorded foods
      and beverages consumed by 496 children in care and calculated healthy eating
      index (HEI) (scores range: 0-100). We used a mixed effects linear regression
      model to examine the association between the EPAO nutrition environment (and EPAO
      sub-scales) and child HEI, controlling for potential confounders. RESULTS: Family
      child care homes had a mean (standard deviation, SD) of 7.2 (3.6) children in
      care, 74.1% of providers were black or African American, and children had a mean
      (SD) age of 35.7 (11.4) months. In adjusted multivariable models, higher EPAO
      nutrition score was associated with increased child HEI score (1.16; 95% CI:
      0.34, 1.98; p = 0.006). Higher scores on EPAO sub-scales for foods provided
      (8.98; 95% CI: 3.94, 14.01; p = 0.0006), nutrition education (5.37; 95% CI: 0.80,
      9.94; p = 0.02), and nutrition policy (2.36; 95% CI: 0.23, 4.49; p = 0.03) were
      all associated with greater child HEI score. CONCLUSIONS: Foods and beverages
      served, in addition to nutrition education and nutrition policies in family child
      care homes, may be promising intervention targets for improving child diet
      quality.

PMID- 29601920
TI  - Eating with others and meal location are differentially associated with nutrient
      intake by sex: The Diabetes Study of Northern California (DISTANCE).
AB  - Though eating with others is often a social behavior, relationships between
      social contexts of eating and nutrient intake have been underexplored. This study
      evaluates how social aspects of eating - frequencies of eating meals with others,
      meals prepared at home, and meals outside the home - are associated with nutrient
      intake. Because diet improvement can reduce complications of diabetes mellitus,
      we surveyed a multi-ethnic cohort of persons with type 2 diabetes (n = 770) about
      social aspects of diet (based on 24-hour recalls). Sex-stratified multiple
      regression analyses adjusted for confounders assessed the relationship between
      frequency of eating with others and nutrient intake (total energy, energy from
      fat, energy from carbohydrates, Healthy Eating Index/HEI, Dietary Approaches to
      Stop Hypertension/DASH score). Although there was slight variation in men's
      versus women's propensity to share meals, after adjustment for confounders, there
      was no consistently significant association between meals with others and the 5
      nutrient intake measures for either men or women. The directions of association
      between categories of eating with others and diet quality (HEI and DASH scores) -
      albeit not significant - were different for men (positive) and women (mostly
      negative), which warrants further investigation. The next analyses estimated
      nutrient intake associated with meals prepared at home, and meals consumed
      outside the home. Analyses indicated that greater meal frequency at home was
      associated with significantly better scores on diet quality indices for men (but
      not women), while meal frequency outside the home was associated with poorer diet
      quality and energy intake for women (but not men). Better measurement of social
      dimensions of eating may inform ways to improve nutrition, especially for persons
      with diabetes for whom diet improvement can result in better disease outcomes.

PMID- 29601922
TI  - Family food involvement is related to healthier dietary intake in preschool-aged
      children.
AB  - Children in the United States fall far short of meeting federal dietary
      recommendations. The unhealthy diets common amongst young children are of crucial
      public health concern, given that they can inhibit healthy development and are
      predictive of chronic diseases in adulthood. Research investigating behaviors
      that are related to dietary habits is crucial to allow a better understanding of
      the causes of unhealthy dietary practices. Involvement in food preparation is
      known to be associated with healthy dietary behaviors in school-aged children,
      but little is known about these behaviors and their correlates in younger
      children. The present study sought to examine the influences and correlates of
      involvement in family food preparation in children at ages three and four.
      Parents of preschool aged children (n = 497) completed surveys including
      information about demographic background, their children's family food
      involvement, dietary intake, mealtime routines, and problematic eating behaviors.
      Data were collected when children were three (wave one of the survey) and four
      years of age (wave two). Findings from this study indicate that family food
      involvement at age three is predictive of healthier dietary intake at age four
      (increased consumption of fruits and vegetables, decreased consumption of fast
      food). These findings indicate that family food involvement is predictive of
      healthier dietary behaviors in young children, and that outreach efforts focused
      on family food involvement in early childhood may improve children's dietary
      habits.

PMID- 29601923
TI  - Evaluation and Management of Testosterone Deficiency: AUA Guideline.
AB  - PURPOSE: There has been a marked increase in testosterone prescriptions in the
      past decade resulting in a growing need to give practicing clinicians proper
      guidance on the evaluation and management of the testosterone deficient patient.
      MATERIALS AND METHODS: A systematic review utilized research from the Mayo Clinic
      Evidence Based Practice Center and additional supplementation by the authors.
      Evidence-based statements were based on body of evidence strength Grade A, B, or
      C and were designated as Strong, Moderate, and Conditional Recommendations with
      additional statements presented in the form of Clinical Principles or Expert
      Opinions (table 1 in supplementary unabridged guideline, http://jurology.com/).
      RESULTS: This guideline was developed by a multi-disciplinary panel to inform
      clinicians on the proper assessment of patients with testosterone deficiency and
      the safe and effective management of men on testosterone therapy. Additional
      statements were developed to guide the clinician on the appropriate care of
      patients who are at risk for or have cardiovascular disease or prostate cancer as
      well as patients who are interested in preserving fertility. CONCLUSIONS: The
      care of testosterone deficient patients should focus on accurate assessment of
      total testosterone levels, symptoms, and signs as well as proper on-treatment
      monitoring to ensure therapeutic testosterone levels are reached and symptoms are
      ameliorated. Future longitudinal observational studies and clinical trials of
      significant duration in this space will improve diagnostic techniques and
      treatment of men with testosterone deficiency as well as provide more data on the
      adverse events that may be associated with testosterone therapy.

PMID- 29601924
TI  - Anterior Urethroplasty Using a New Tissue Engineered Oral Mucosa Graft: Surgical
      Techniques and Outcomes.
AB  - PURPOSE: We investigated whether tissue engineered material may be adopted using
      standard techniques for anterior urethroplasty. MATERIALS AND METHODS: We
      performed a retrospective multicenter study in patients with recurrent
      strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic
      and posterior strictures. A 0.5 cm2 oral mucosa biopsy was taken from the patient
      cheek and sent to the laboratory to manufacture the graft. After 3 weeks the
      tissue engineered oral mucosal MukoCell(r) graft was sent to the hospital for
      urethroplasty. Four techniques were used, including ventral onlay, dorsal onlay,
      dorsal inlay and a combined technique. Cystourethrography was performed 1 month
      postoperatively. Patients underwent clinical evaluation, uroflowmetry and post
      void residual urine measurement every 6 months. When the patient showed
      obstructive symptoms, defined as maximum urine flow less than 12 ml per second,
      the urethrography was repeated. Patients who underwent further treatment for
      recurrent stricture were classified as having treatment failure. RESULTS: Of the
      38 patients with a median age of 57 years who were included in study the
      strictures were penile in 3 (7.9%), bulbar in 29 (76.3%) and penobulbar in 6
      (15.8%). Median stricture length was 5 cm and median followup was 55 months.
      Treatment succeeded in 32 of the 38 patients (84.2%) and failed in 15.8%. Success
      was achieved in 85.7% of ventral onlay, 83.3% of dorsal onlay, 80% of dorsal
      inlay and 100% of combined technique cases. No local or systemic adverse
      reactions due to the engineered material were noted. CONCLUSIONS: Our findings
      show that a tissue engineered oral mucosa graft can be implanted using the same
      techniques suggested for anterior urethroplasty and native oral mucosa, and
      guaranteeing a similar success rate.

PMID- 29601925
TI  - The Most Important Lesson I Learned this Year.

PMID- 29601926
TI  - The Value of Reflection in Urological Training: An Introduction to the AUA
      Residents and Fellows Committee Essay Contest.

PMID- 29601927
TI  - Genetic alterations in the NO-cGMP pathway and cardiovascular risk.
AB  - In the past ten years, several chromosomal loci have been identified by genome
      wide association studies to influence the risk of coronary artery disease (CAD)
      and its risk factors. The GUCY1A3 gene encoding the alpha1 subunit of the soluble
      guanylyl cyclase (sGC) resides at one of these loci and has been strongly
      associated with blood pressure and CAD risk. More recently, further genes in the
      pathway encoding the endothelial nitric oxide synthase, the phosphodiesterases 3A
      and 5A, and the inositol 1,4,5-trisphosphate receptor I-associated protein
      (IRAG), i.e., NOS3, PDE3A, PDE5A, and MRVI1, respectively, were likewise
      identified as CAD risk genes. In this review, we highlight the genetic findings
      linking variants in NO-cGMP signaling and cardiovascular disease, discuss the
      potential underlying mechanisms which might propagate the development of
      atherosclerosis, and speculate about therapeutic implications.

PMID- 29601928
TI  - Biological properties of nitro-fatty acids in plants.
AB  - Nitro-fatty acids (NO2-FAs) are formed from the reaction between nitrogen dioxide
      (NO2) and mono and polyunsaturated fatty acids. Knowledge concerning NO2-FAs has
      significantly increased within a few years ago and the beneficial actions of
      these species uncovered in animal systems have led to consider them as molecules
      with therapeutic potential. Based on their nature and structure, NO2-FAs have the
      ability to release nitric oxide (NO) in aqueous environments and the capacity to
      mediate post-translational modifications (PTM) by nitroalkylation. Recently,
      based on the potential of these NO-derived molecules in the animal field, the
      endogenous occurrence of nitrated-derivatives of linolenic acid (NO2-Ln) was
      assessed in plant species. Moreover and through RNA-seq technology, it was shown
      that NO2-Ln can induce a large set of heat-shock proteins (HSPs) and different
      antioxidant systems suggesting this molecule may launch antioxidant and defence
      responses in plants. Furthermore, the capacity of this nitro-fatty acid to
      release NO has also been demonstrated. In view of this background, here we offer
      an overview on the biological properties described for NO2-FAs in plants and the
      potential of these molecules to be considered new key intermediaries of NO
      metabolism in the plant field.

PMID- 29601929
TI  - 6-OHBDE-47 induces transcriptomic alterations of CYP1A1, XRCC2, HSPA1A, EGR1
      genes and trigger apoptosis in HepG2 cells.
AB  - In this study, HepG2 cells were exposed to 6-hydroxy- 2,2',4,4'
      tetrabromodiphenyl ether (6-OH-BDE-47) for 3 and 6 days for monitoring cytotoxic
      effects and alterations in its transcriptomic profile. MTT assay showed that
      cells exposed to 6-OH-BDE-47 (50 nM) exhibited 48.5% and 53.7% decline in cell
      survival after 3 and 6 days. Neutral red uptake (NRU) assay also demonstrated
      47.1% and 56% reduction in cell survival at 50 nM, indicating lysosomal toxicity.
      The flow cytometric data confirmed an increase in intracellular reactive oxygen
      species (ROS) and mitochondrial dysfunction (DeltaPsim). In comet assay, HepG2
      cells exposed to 6-OH-BDE-47 (50 nM) showed 7.6-fold greater DNA damage. Cell
      cycle data revealed G2/M arrest at 10 and 25 nM after 3 days of exposure, while
      50 nM induced mild apoptotic effect. The intensity of apoptosis increased after 6
      days of exposure with 21.5%, 47% and 99.1% of cells recorded in subG1 apoptotic
      phase vis-a- vis the control showed 14.5% background apoptotic cells.
      Transcriptome analysis of 6-OH-BDE-47 (25 nM, 3 days) treated cells revealed
      cross talk between vital pathways. Especially, the genes involved in oxidative or
      metabolic stress, heat shock, growth arrest and senescence were differentially up
      and down regulated to orchestrate the cellular toxicity and triggering apoptosis
      in HepG2 cells.

PMID- 29601930
TI  - Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia:
      An investigation on potential interactions.
AB  - Peritoneal dialysis (PD) performed with transmembrane pH-gradient liposomes was
      reported to efficiently remove ammonia from the body, representing a promising
      alternative to current standard-of-care for patients with severe hepatic
      encephalopathy. In this study, we further characterized the properties of
      liposome-supported peritoneal dialysis (LSPD) by 1) assessing its in-use
      stability in the presence of ascitic fluids from liver-disease patients; 2)
      investigating its interactions with drugs that are commonly administered to acute
      on-chronic liver failure patients; and 3) analyzing the in vivo extraction
      profile of LSPD. We found that LSPD fluid maintained its in vitro ammonia uptake
      capability when combined with ascitic fluids. The co-incubation of selected drugs
      (e.g., beta-blockers, antibiotics, diuretics) with LSPD fluids and ammonia
      resulted in limited interaction effects for most compounds except for two
      fluoroquinolones and propranolol. However, considering the experimental set-up,
      these results should be interpreted with caution and confirmatory drug-drug
      interaction studies in a clinical setting will be required. Finally, metabolite
      mapping analysis on dialysates of LSPD-treated rats revealed that the liposomes
      did not remove important metabolites more than a conventional PD fluid. Overall,
      these findings confirm that LSPD is a potentially safe and effective approach for
      treating hyperammonemic crises in the context of acute-on-chronic liver failure.

PMID- 29601931
TI  - Systems for localized release to mimic paracrine cell communication in vitro.
AB  - Paracrine cell communication plays a pivotal role for signal exchange between
      proximal cells in vivo. However, this localized, gradient type release of
      mediators at very low concentrations (pg/ml), relevant during physiological and
      pathological processes, is rarely reflected within in vitro approaches. This
      review gives an overview on state-of-the-art approaches, which transfer the
      paracrine cell-to-cell communication into in vitro cell culture model setups. The
      traditional methods like trans-well assays and more advanced microfluidic
      approaches are included. The review focusses on systems for localized release,
      mostly based on microparticles, which tightly mimic the paracrine interaction
      between single cells in 3D microenvironments. Approaches based on single
      microparticles, with the main focus on affinity-controlled storage and release of
      cytokines, are reviewed and their importance for understanding paracrine
      communication is highlighted. Various methods to study the cytokine release and
      their advantages and disadvantages are discussed. Basic principles of the release
      characteristics, like diffusion mechanisms, are quantitatively described,
      including the formation of resulting gradients around the local sources. In vitro
      cell experiments using such localized microparticle release systems in approaches
      to increase understanding of stem cell behavior within their niches and
      regulation of wound healing are highlighted as examples of successful localized
      release systems for mimicking paracrine cell communication.

PMID- 29601933
TI  - Ex vivo evaluation of cytotoxicity and melanocyte viability after A-101 hydrogen
      peroxide topical solution 40% or cryosurgery treatment in seborrheic keratosis
      lesions.

PMID- 29601932
TI  - Sequential intracellular release of water-soluble cargos from Shell-crosslinked
      polymersomes.
AB  - Polymer vesicles, i.e. polymersomes (PS), present unique nanostructures with an
      interior aqueous core that can encapsulate multiple independent cargos
      concurrently. However, the sequential release of such co-loaded actives remains a
      challenge. Here, we report the rational design and synthesis of oxidation
      responsive shell-crosslinked PS with capability for the controlled, sequential
      release of encapsulated hydrophilic molecules and hydrogels. Amphiphilic brush
      block copolymers poly(oligo(ethylene glycol) methyl ether methacrylate)-b
      poly(oligo(propylene sulfide) methacrylate) (POEGMA-POPSMA) were prepared to
      fabricate PS via self-assembly in aqueous solution. As a type of unique drug
      delivery vehicle, the interior of the PS was co-loaded with hydrophilic molecules
      and water-soluble poly(N-isopropylacrylamide) (PNIPAM) conjugates. Due to the
      thermosensitivity of PNIPAM, PNIPAM conjugates within the PS aqueous interior
      underwent a phase transition to form hydrogels in situ when the temperature was
      raised above the lower critical solution temperature (LCST) of PNIPAM. Via
      control of the overall shell permeability by oxidation, we realized the
      sequential release of two water-soluble payloads based on the assumption that
      hydrogels have much smaller membrane permeability than that of molecular cargos.
      The ability to control the timing of release of molecular dyes and PNIPAM-based
      hydrogels was also observed within live cells. Furthermore, leakage of hydrogels
      from the PS was effectively alleviated in comparison to molecular cargos, which
      would facilitate intracellular accumulation and prolonged retention of hydrogels
      within the cell cytoplasm. Thus, we demonstrate that the integration of
      responsive hydrogels into PS with crosslinkable membranes provides a facile and
      versatile technique to control the stability and release of water-soluble cargos
      for drug delivery purposes.

PMID- 29601934
TI  - Malignant melanoma associated with chronic once-daily aspirin exposure in males:
      A large, single-center, urban, US patient population cohort study from the
      "Research on Adverse Drug events And Report" (RADAR) project.

PMID- 29601935
TI  - A healthy diet in women is associated with less facial wrinkles in a large Dutch
      population-based cohort.
AB  - BACKGROUND: Little is known about the effects of different dietary patterns on
      facial wrinkling. OBJECTIVE: We aimed to investigate the association between diet
      and facial wrinkles in a population-based cohort of 2,753 elderly participants of
      the Rotterdam Study. METHODS: Wrinkles were digitally quantified as the area in
      facial photographs they occupied as a percentage of the total skin area. Diet was
      assessed using the Food Frequency Questionnaire. Adherence to the Dutch Healthy
      Diet Index (DHDI) was calculated. In addition, we used Principal Component
      Analysis (PCA) to extract relevant food patterns in men and women separately. All
      food patterns and the DHDI were analyzed for association with wrinkle severity
      using multivariable linear regression. RESULTS: Better adherence to the Dutch
      guidelines was significantly associated with less wrinkles among women but not in
      men. In women, a red meat and snack dominant PCA pattern was associated with more
      facial wrinkles whereas a fruit dominant PCA pattern associated with fewer
      wrinkles. LIMITATIONS: Due to the cross-sectional design of our study, no
      causation can be proved. Health-conscious behavior could have influenced our
      results. CONCLUSION: Dietary habits associate with facial wrinkling in women.
      Global disease prevention strategies might benefit from emphasizing that a
      healthy diet is also linked to less facial wrinkling.

PMID- 29601936
TI  - Wound care for Stevens-Johnson syndrome and toxic epidermal necrolysis.

PMID- 29601937
TI  - Subungual atypical lentiginous melanocytic proliferations in children and
      adolescents: A clinicopathologic study.
AB  - BACKGROUND: Most subungual melanocytic lesions in children are benign, but some
      are difficult to classify due to prominent lentiginous growth and high-grade
      cytologic atypia. OBJECTIVE: To characterize the clinicopathologic features of
      these rare lesions. METHODS: Subungual atypical lentiginous melanocytic
      proliferations from patients <20 years of age were collected for clinical and
      histopathologic review. Fluorescence in situ hybridization (FISH) was performed
      when possible. RESULTS: Eleven patients aged 2-19 years had expanding or
      darkening longitudinal pigmented streak(s) with or without Hutchinson sign.
      Microscopically, all revealed predominantly single-cell growth, pagetoid scatter,
      and poor circumscription. Eight (73%) cases showed focal or poor nesting, and 3
      (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and
      angulation were present in 8 (73%) cases, 7 (64%) cases, and 6 (55%) cases,
      respectively. One of 4 cases tested by FISH was positive. Three lesions recurred
      locally without other adverse outcome. LIMITATIONS: Small sample size and short
      clinical follow-up. Two cases were examined in partial biopsies only. CONCLUSION:
      Some subungual melanocytic lesions in children and adolescents are histologically
      indistinguishable from adult subungual melanoma in situ. While the biologic
      potential remains elusive, FISH might aid in risk stratification. Awareness of
      this rare group of lesions is crucial for facilitating future investigation into
      its biologic behavior.

PMID- 29601938
TI  - Gene silencing of ZnT8 attenuates inflammation and protects pancreatic tissue
      injury in T1D.
AB  - T lymphocyte mediated inflammation contributes to the development of T1D. Zinc
      Transporter 8 (ZnT8) has emerged as a target of autoreactive T cells in human T1D
      in recent years. However, the regulating of ZnT8 in T1D has not been identified.
      We make a hypothesis that whether alternation of ZnT8 level could attenuate
      inflammation and protect pancreatic tissue injury in T1D. In this study, we
      utilized ZnT8 shRNA to inhibit ZnT8 expression, and detected inflammation,
      glucose tolerance and pancreatic tissue of NOD mice. We found that ZnT8 shRNA
      attenuated specific CD8+ T cell activation and cytotoxicity. In addition, ZnT8
      shRNA protected glucose tolerance and pancreatic tissue injury via down
      regulation of ZnT8 in NOD mice. Therefore, the results suggest that RNAi
      represents a promising target reducing ZnT8 mediated inflammation, and provides a
      novel therapeutical clue in T1D.

PMID- 29601939
TI  - DEC1/STRA13 is a key negative regulator of activation-induced proliferation of
      human B cells highly expressed in anergic cells.
AB  - The transcription factor DEC1/STRA13 (also known as BHLHE40 and SHARP2) is
      involved in a number of processes including inhibition of cell proliferation and
      delay of cell cycle, and is a negative regulator of B cell activation and
      development in mice. We show here that, unlike in mice, DEC1/STRA13 expression is
      induced in human naive and memory resting B cells by activation through the B
      cell receptor (BCR) or Toll-like receptor 9 (TLR9). siRNA silencing of
      DEC1/STRA13 increases the capacity of activated B cells to perform a high number
      of divisions after TLR9 ligation. This identifies DEC1/STRA13 as a critical
      negative regulator of clonal expansion of activated human B cells. We also show
      that DEC1/STRA13 is upregulated in human anergic CD21low B cells clonally
      expanded in patients with HCV-associated mixed cryoglobulinemia, which fail to
      proliferate in response to BCR or TLR9 ligation. siRNA knockdown of DEC1/STRA13,
      however, fails to restore responsiveness to stimuli in these cells, although it
      might improve the proliferative capacity in a subset of anergic cells with less
      pronounced proliferative defect.

PMID- 29601940
TI  - Novel intranasal pertussis vaccine based on bacterium-like particles as a mucosal
      adjuvant.
AB  - Pertussis, or whooping cough, has recently reemerged as a major public health
      threat despite high levels of vaccination. The development of a novel pertussis
      vaccine, especially an intranasal (i.n.) vaccine is undoubtedly necessary, and
      mucosal adjuvants have been explored to enhance the immune response. In the
      present study, bacterium-like particles (BLPs) were adopted as a mucosal adjuvant
      for an i.n. pertussis vaccine and evaluated on the ability to induce serum and
      mucosal antibodies as well as potency against i.n. challenge in mice. Groups with
      or without aluminum adjuvant were also evaluated through both i.n. and
      intraperitoneal inoculations. Vaccination with BLPs via the i.n. route led to
      rapid IgG and IgA production and provided strong protection against inflammation
      induced by infection. The results support an i.n. pertussis vaccine with BLPs
      adjuvant as a promising candidate to elicit protective immunity against whooping
      cough.

PMID- 29601941
TI  - Different profile of cytokine production in patients with systemic sclerosis and
      association with clinical manifestations.
AB  - Immune dysregulation is a central process in the pathogenesis of systemic
      sclerosis (SSc). Cytokines produced by lymphocytes and monocytes are important
      mediators and induce tissue damage, recruit additional inflammatory cells, and
      promote extracellular matrix production and fibrosis. In the present research, we
      aimed to study the associations between levels of cytokines in serum and culture
      supernatants from peripheral blood mononuclear cells (PBMCs) and clinical
      manifestations in SSc patients. Serum samples were obtained from 56 SSc patients
      and 56 unrelated age- and gender-matched healthy individuals. Resting and anti
      CD3/CD28-stimulated PBMC cultures were obtained from 19 SSc patients and 8
      healthy controls. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, and IFN-gamma levels were
      measured by ELISA or CBA. Serum cytokines, except IL-17A, were below the kit
      detection limit in most of the patients and controls. In unstimulated PBMC, the
      production of TNF(p = 0.004), IL-10(p = .048), IL-2(p < 0.001), and IL-6 (p =
      0.01) was higher in SSc patients than in healthy controls. After anti-CD3/CD28
      stimulation, scleroderma PBMCs had lower concentrations of TNF(p = 0.009), IL
      10(p = .018), and IL-2(p = .002) than HC. In unstimulated PBMC, IL-2
      concentration was higher in patients with esophageal dysmotility (p = 0.04), and
      IL-10 levels had a positive correlation with modified Rodnan score (p = 0.03).
      After anti-CD3/CD28 stimulation, higher levels of IL-2 and IL-4 were observed in
      SSc patients with lung fibrosis (p = 0.01 and 0.006, respectively), and higher
      levels of IL-10 (p = 0.04) and IL-4 (p = 0.04) in patients with digital ulcers.
      In conclusion, SSc patients have a different profile of cytokine production and
      this was associated with clinical manifestations.

PMID- 29601942
TI  - Effects of Toll-like receptor 4 on beta2-glycoprotein I-induced splenic T cell
      subsets differentiation.
AB  - Our previous study demonstrated that beta 2-glycoprotein I (beta2GPI) stimulation
      promotes bone marrow derived dendritic cells (BMDCs) maturation and T cell
      proliferation in a Toll-like receptor 4 (TLR4) dependent manner. However,
      beta2GPI induced T cell differentiation and the role of TLR4 in this process have
      rarely been reported. In the present study, we focused on the differentiation of
      splenic T cells in beta2GPI immunized Balb/c, C3H/HeN and C3H/HeJ mice. According
      to our results, Th2 dominated differentiation was observed in beta2GPI immunized
      Balb/c and C3H/HeN mice than in those treated with normal saline (NS), namely the
      up-regulated levels of Th2 markers GATA3 and IL-4 (p < 0.05). Meanwhile, reduced
      Th1 markers T-bet and IFN-gamma, and Treg marker Foxp3 were observed in beta2GPI
      immunized mice (p < 0.05). C3H/HeJ mice have the same gene background with
      C3H/HeN mice except a functional mutant in TLR4 gene. However, the described Th2
      differentiation was not detected in these TLR4 deficient mice, indicating the
      importance of TLR4 in immune response against beta2GPI. In addition, we found
      that beta2GPI-induced Th2 differentiation could be strengthened by cytokines
      secreted by dendritic cells (DCs) and DCs-T cells interaction. However, DCs-T
      cells contact was indispensable during this process because of its unique role in
      suppressing Th1 function. Furthermore, this Th2 biased differentiation pattern
      was more noticeable in mice received 4 times beta2GPI immunization than those
      received 2 times, suggesting the amplifying effects of anti-beta2GPI Ab on
      beta2GPI induced Th2 response. These findings may partly explain the immune
      imbalance in APS patient through the view angle of T cell differentiation and
      anti-beta2GPI antibody production.

PMID- 29601944
TI  - Cellular players that shape evolving pathology and neurodegeneration following
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death and disability
      worldwide, and has emerged as a critical risk factor for multiple
      neurodegenerative diseases, particularly Alzheimer's disease (AD). How the
      inflammatory cascade resulting from mechanical stress, axonal shearing and the
      loss of neurons and glia following initial impact in TBI, contributes to the
      development of AD-like disease is unclear. Neuroinflammation, characterized by
      blood-brain barrier (BBB) dysfunction and activation of brain-resident microglia
      and astrocytes, resulting in secretion of inflammatory mediators and subsequent
      recruitment of peripheral immune cells has been the focus of extensive research
      in attempts to identify drug-targets towards improving functional outcomes post
      TBI. While knowledge of intricate cellular interactions that shape lesion
      pathophysiology is incomplete, a major limitation in the field is the lack of
      understanding of how distinct cell types differentially alter TBI pathology. The
      aim of this review is to highlight functional differences between populations of
      bone marrow derived, infiltrating monocytes/macrophages and brain-resident
      microglia based on differential expression of the chemokine receptors CCR2 and
      CX3CR1. This review will focus on how unique subsets of mononuclear phagocytes
      shape TBI pathophysiology, neurotoxicity and BBB function, in a disease-stage
      dependent manner. Additionally, this review summarizes the role of multiple
      microglia and macrophage receptors, namely CCR2, CX3CR1 and Triggering Receptor
      Expressed on Myeloid Cells-2 (TREM2) in pathological neuroinflammation and
      neurodegeneration vs. recovery following TBI. TREM2 has been implicated in
      mediating AD-related pathology, and variants in TREM2 are particularly important
      due to their correlation with exacerbated neurodegeneration. Finally, this review
      highlights behavioral outcomes associated with microglial vs. macrophage
      variances, the need for novel treatment strategies that target unique
      subpopulations of peripheral macrophages, and the importance of development of
      therapeutics to modulate inflammatory functions of brain-resident microglia at
      specific stages of TBI.

PMID- 29601945
TI  - Hypoxia, oxidative stress and inflammation.
AB  - Inflammatory Arthritis is characterized by synovial proliferation,
      neovascularization and leukocyte extravasation leading to joint destruction and
      functional disability. Efficiency of oxygen supply to the synovium is poor due to
      the highly dysregulated synovial microvasculature. This along with the increased
      energy demands of activated infiltrating immune cells and inflamed resident cells
      leads to an hypoxic microenvironment and mitochondrial dysfunction. This favors
      an increase of reactive oxygen species, leading to oxidative damage which further
      promotes inflammation. In this adverse microenvironment synovial cells adapt to
      generate energy and switch their cell metabolism from a resting regulatory state
      to a highly metabolically active state which allows them to produce essential
      building blocks to support their proliferation. This metabolic shift results in
      the accumulation of metabolic intermediates which act as signaling molecules that
      further dictate the inflammatory response. Understanding the complex interplay
      between hypoxia-induced signaling pathways, oxidative stress and mitochondrial
      function will provide better insight into the underlying mechanisms of disease
      pathogenesis.

PMID- 29601943
TI  - Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus
      solitarii via discrete age-dependent mechanisms in neonatal rats.
AB  - Transition periods (TPs) are brief stages in CNS development where neural
      circuits can exhibit heightened vulnerability to pathologic conditions such as
      injury or infection. This susceptibility is due in part to specialized mechanisms
      of synaptic plasticity, which may become activated by inflammatory mediators
      released under pathologic conditions. Thus, we hypothesized that the immune
      response to lung injury (LI) mediated synaptic changes through plasticity-like
      mechanisms that depended on whether LI occurred just before or after a TP. We
      studied the impact of LI on brainstem 2nd-order viscerosensory neurons located in
      the nucleus tractus solitarii (nTS) during a TP for respiratory control spanning
      (postnatal day (P) 11-15). We injured the lungs of Sprague-Dawley rats by
      intratracheal instillation of Bleomycin (or saline) just before (P9-11) or after
      (P17-19) the TP. A week later, we prepared horizontal slices of the medulla and
      recorded spontaneous and evoked excitatory postsynaptic currents (sEPSCs/eEPSCs)
      in vitro from neurons in the nTS that received monosynaptic glutamatergic input
      from the tractus solitarii (TS). In rats injured before the TP (pre-TP), neurons
      exhibited blunted sEPSCs and TS-eEPSCs compared to controls. The decreased TS
      eEPSCs were mediated by differences in postsynaptic alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic-acid receptors (AMPAR). Specifically, compared to
      controls, LI rats had more Ca2+-impermeable AMPARs (CI-AMPARs) as indicated by:
      1) the absence of current-rectification, 2) decreased sensitivity to polyamine, 1
      Naphthyl-acetyl-spermine-trihydrochloride (NASPM) and 3) augmented immunoreactive
      staining for the CI-AMPAR GluA2. Thus, pre-TP-LI acts postsynaptically to blunt
      glutamatergic transmission. The neuroimmune response to pre-TP-LI included
      microglia hyper-ramification throughout the nTS. Daily intraperitoneal
      administration of minocycline, an inhibitor of microglial/macrophage function
      prevented hyper-ramification and abolished the pre-TP-LI evoked synaptic changes.
      In contrast, rat-pups injured after the TP (post-TP) exhibited microglia hypo
      ramification in the nTS and had increased sEPSC amplitudes/frequencies, and
      decreased TS-eEPSC amplitudes compared to controls. These synaptic changes were
      not associated with changes in CI-AMPARs, and instead involved greater TS-evoked
      use-dependent depression (reduced paired pulse ratio), which is a hallmark of
      presynaptic plasticity. Thus we conclude that LI regulates the efficacy of TS ->
      nTS synapses through discrete plasticity-like mechanisms that are immune-mediated
      and depend on whether the injury occurs before or after the TP for respiratory
      control.

PMID- 29601947
TI  - Imaging the secretory compartments involved in the intracellular traffic of CHS
      4, a class IV chitin synthase, in Neurospora crassa.
AB  - In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs)
      at the Spitzenkorper (SPK) and at developing septa has been well analyzed.
      Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery
      sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from
      the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the
      role of CSE-7, N. crassa Chs7p orthologue, in the biogenesis of CHS-4 (orthologue
      of Chs3p). In a N. crassa Deltacse-7 mutant, CHS-4-GFP no longer accumulated at
      the SPK and septa. Instead, fluorescence was retained in hyphal subapical regions
      in an extensive network of elongated cisternae (NEC) referred to previously as
      tubular vacuoles. In a complemented strain expressing a copy of cse-7 the
      localization of CHS-4-GFP at the SPK and septa was restored, providing evidence
      that CSE-7 is necessary for the localization of CHS-4 at hyphal tips and septa.
      CSE-7 was revealed at delimited regions of the ER at the immediacies of nuclei,
      at the NEC, and remarkably also at septa and the SPK. The organization of the NEC
      was dependent on the cytoskeleton. SEC-63, an extensively used ER marker, and NCA
      1, a SERCA-type ATPase previously localized at the nuclear envelope, were used as
      markers to discern the nature of the membranes containing CSE-7. Both SEC-63 and
      NCA-1 were found at the nuclear envelope, but also at regions of the NEC.
      However, at the NEC only NCA-1 co-localized extensively with CSE-7. Observations
      by transmission electron microscopy revealed abundant rough ER sheets and
      distinct electron translucent smooth flattened cisternae, which could correspond
      collectively to the NEC, thorough the subapical cytoplasm. This study identifies
      CSE-7 as the putative ER receptor for its cognate cargo, the polytopic membrane
      protein CHS-4, and elucidates the complexity of the ER system in filamentous
      fungi.

PMID- 29601946
TI  - Calculated cell-specific intracellular hydrogen peroxide concentration: Relevance
      in cancer cell susceptibility during ascorbate therapy.
AB  - The high extracellular hydrogen peroxide (H2O2) concentrations generated during
      pharmacological ascorbate (P-AscH-) therapy has been shown to exhibit a high flux
      into susceptible cancer cells leading to a decrease in clonogenic survival. It is
      hypothesized that the intracellular H2O2 concentration for susceptibility is
      independent of cell type and that the variation observed in dosing is associated
      with differences in the cell-specific overall steady-state intracellular H2O2
      concentration values. The steady-state variation in intracellular H2O2
      concentration is coupled to a number of cellular specific transport and reaction
      factors including catalase activity and membrane permeability. Here a lumped
      parameter mathematical modeling approach, assuming a catalase-dominant peroxide
      removal mechanism, is used to calculate intracellular H2O2 concentration for
      several cell lines. Experimental measurements of critical parameters pertaining
      to the model are obtained. The cell lines investigated are normal pancreatic
      cells, H6c7, the pancreatic cancer cell line, MIA PaCa-2 and the glioblastoma
      cell lines, LN-229, T98G, and U-87; all which vary in susceptibility. The
      intracellular H2O2 concentration estimates are correlated with the clonogenic
      surviving fraction for each cell line, in-vitro. The results showed that, despite
      the fact that the experimental parameters including catalase concentration and
      plasma membrane permeability demonstrated significant variability across cell
      lines, the calculated steady-state intracellular to extracellular H2O2
      concentration ratio did not vary significantly across cell lines. Thus, the
      calculated intracellular H2O2 concentration is not unique in characterizing
      susceptibility. These results imply that, although intracellular H2O2
      concentration plays a key role in cellular susceptibility to P-AscH- adjuvant
      therapy, its overall contribution in a unifying mechanism across cell types is
      complex.

PMID- 29601948
TI  - Microarray analysis of obese women with polycystic ovary syndrome for key gene
      screening, key pathway identification and drug prediction.
AB  - PURPOSE: This study aimed to screen key genes and pathways involved in obese
      polycystic ovary syndrome (PCOS), and predict drugs for treatment of obese PCOS
      via bioinformatics approaches. METHODS: Microarray dataset GSE10946 were
      downloaded from the Gene Expression Omnibus database, including 7 cumulus cell
      samples from obese PCOS patients and 6 lean control samples. Differentially
      expressed genes (DEGs) between obese PCOS and controls were obtained using
      Bayesian test after data preprocessing, followed by functional enrichment
      analyses for DEGs. Besides, protein-protein interaction (PPI) network and sub
      network analyses were performed. Furthermore, drug prediction was carried out
      based on the DEGs. RESULTS: A total of 793 DEGs were identified in PCOS compared
      with control, including 352 up-regulated and 441 down-regulated DEGs.
      Specifically, upregulated RNA polymerase I subunit B (POLR1B), DNA polymerase
      epsilon 3, accessory subunit (POLE3), and DNA polymerase delta 3, accessory
      subunit (POLD3) were enriched in pathway of pyrimidine metabolism associated with
      obesity and PCOS, and 5-hydroxytryptamine receptor 2C (HTR2C) was enriched
      calcium signaling pathway. Additionally, 10 significant potential drugs, such as
      spironolactone targeting androgen receptor (AR), trimipramine targeting
      adrenoceptor beta 2 (ADRB2), and L-ornithine targeting ornithine decarboxylase
      antizyme 3 (OAZ3), were obtained. CONCLUSIONS: In conclusion, POLR1B, POLE3,
      POLD3, and HTR2C might play important roles in obese PCOS via involvement of
      pyrimidine metabolism and calcium signaling pathway. Moreover, AR, ADRB2, and
      OAZ3 might be targets of spironolactone, trimipramine, and L-ornithine in the
      treatment of obese PCOS.

PMID- 29601949
TI  - Association study of SREBF-2 gene polymorphisms and the risk of type 2 diabetes
      in a sample of Iranian population.
AB  - Type 2 diabetes mellitus (T2D) as an important metabolic disorder is accompanied
      by dysregulation in lipid metabolism. Sterol regulatory element-binding factor-2
      (SREBF-2) gene has a substantive role in lipid metabolism. Recently published
      report indicated the overexpression of this gene in diabetic patients. So, in
      this preliminary study we evaluated the effects of three common single nucleotide
      polymorphisms (SNPs), rs1052717G/A, rs2267439C/T, and rs2267443G/A in risk of T2D
      in a sample of Iranian population. Present case-control study consists of 250
      patients with endocrinologically approved T2D and 250 healthy controls. The
      variants genotyped by using tetra amplification refractory mutation system
      polymerase chain reaction (Tetra ARMS-PCR) method. The findings demonstrated that
      the rs2267439C/T polymorphism increased the risk of T2D in all measured
      inheritance models (Codominant1; p = 0.003, codominant2; p = 0.014, dominant; p <
      0.0001, recessive; p = 0.037, over-dominant; p = 0.0025, and log-additive; p =
      0.0048) while our results did not show statistically association between
      rs1052717G/A and rs2267443G/A SNPs and T2D development. The current investigation
      indicated that the rs2267439C/T polymorphism in the SREBF-2 gene increased the
      T2D susceptibility in an Iranian population. Further studies with different
      ethnicities and more extensive sample sizes are demanded to confirm our finding.

PMID- 29601950
TI  - Association between MDR1/CYP3A4/OPRM1 gene polymorphisms and the post-caesarean
      fentanyl analgesic effect on Chinese women.
AB  - OBJECTIVE: Our study aimed to evaluate the association between the multidrug
      resistance 1 (MDR1)/cytochrome P450 3A4 (CYP3A4)/MU-opioid receptor (OPRM1) gene
      polymorphisms and the post-caesarean analgesic effect of fentanyl on Chinese
      women. METHODS: We recruited 240 patients who received lower segment caesarean
      section surgeries. Sanger sequencing was used to analyze the MDR11236C >
      T/CYP3A4*1G/OPRM1A118G polymorphisms. We evaluated post-operative fentanyl
      consumption and the effect of intravenous analgesia in patients with different
      genotypes. RESULTS: 1. Subjects with the TT genotype at the 1236C > T
      polymorphism in the MDR1 gene consumed significantly more fentanyl than that
      consumed by subjects with the CC and CT genotypes in the first post-operative 24
      h and 48 h (P < 0.05), and the MAP/HR/Cor/Ang-1 levels gradually increased
      immediately after surgery and in the first post-operative 24 h. 2. Subjects with
      the CYP3A4*1G/*1G genotype needed less fentanyl to achieve pain control than that
      needed by subjects carrying the CYP3A4*1/*1 and CYP3A4*1/*1G genotypes in the
      first post-operative 24 h and 48 h (P < 0.05), and the MAP/HR/Cor/Ang-1 levels
      gradually decreased immediately after surgery and in the first post-operative 24
      h. 3. Subjects with the GG genotype at the A118G polymorphism in the OPRM1 gene
      consumed significantly more fentanyl than that consumed by subjects with the AA
      and AG genotypes in the first post-operative 24 h and 48 h (P < 0.05), and the
      MAP/HR/Cor/Ang-1 levels gradually increased immediately after surgery and in the
      first post-operative 24 h. 4. There were no significant differences in the
      adverse reactions to fentanyl in patients with different genotypes (P > 0.05).
      CONCLUSION: These results indicated that the MDR1/CYP3A4/OPRM1 gene polymorphisms
      influenced the fentanyl consumption and the physiological effects of intravenous
      analgesia in the Chinese women who received lower segment caesarean section
      surgeries. Moreover, the present study provides an important foundation and
      theoretical evidence for the gene-directed rationalization and individualization
      of medication before caesarean section surgeries.

PMID- 29601951
TI  - Genome-wide identification of lectin receptor kinases in pear: Functional
      characterization of the L-type LecRLK gene PbLRK138.
AB  - Lectin receptor-like kinases (LecRLKs) are membrane-bound receptors that are
      believed to be involved in biotic and abiotic stress responses. However, little
      is known about the LecRLK family in pear. In this study, a total of 172 LecRLK
      genes were first identified in the entire pear genome. The 172 LecRLKs were
      divided into three types (111 G-, 59 L- and two C-types) based on their structure
      and phylogenetic relationships. LecRLKs gene expressions were detected in
      different pear tissues including roots, stems, leaves, flowers and fruits, and
      the most of the 11 selected LecRLKs exhibited similar expression patterns.
      Furthermore, six selected LecRLKs were shown to be involved in salt stress
      response. Overexpression of PbLRK138, an L-type LecRLK, caused cell death and
      induced expression of defense-related genes in Nicotiana benthamiana. Two
      deletion mutants containing lectin or transmembrane and serine/threonine kinase
      domains did not trigger cell death. In addition, only the mutant with the
      transmembrane domain was localized to the plasma membrane.

PMID- 29601952
TI  - Muscarinic modulation of the Xenopus laevis tadpole spinal mechanosensory
      pathway.
AB  - Muscarinic acetylcholine receptors (mAChRs) mediate effects of acetylcholine
      (ACh) in many systems, including those involved in spinal functions like
      locomotion. In Xenopus laevis tadpoles at two days old, a model vertebrate for
      motor control research, we investigated the role of mAChRs in the skin
      mechanosensory pathway. We found that mAChR activation by carbachol did not
      affect the sensory Rohon-Beard neuron properties. However, carbachol could
      hyperpolarise sensory interneurons and decrease their voltage responses to
      outward currents. Carbachol could increase the threshold for the mechanosensory
      pathway to start swimming, preventing the initiation of swimming at higher
      concentrations altogether. Recording from the sensory interneurons in carbachol
      showed that their spiking after skin stimulation was depressed. However, the
      general muscarinic antagonist atropine did not have a clear effect on the
      swimming threshold or the modulation of sensory interneuron membrane conductance.
      Our results suggest the skin mechanosensory pathway may be subject to muscarinic
      modulation in this simple vertebrate system.

PMID- 29601954
TI  - Functional neuroimaging of recovery from motor conversion disorder: A case
      report.
AB  - A patient with motor conversion disorder presented with a functional paresis of
      the left hand. After exclusion of structural brain damage, she was repeatedly
      examined with whole-brain functional magnetic resonance imaging, while she
      performed visually paced finger-tapping tasks. The dorsal premotor cortex showed
      a bilateral deactivation in the acute-subacute phase. Recovery from unilateral
      hand paresis was associated with a gradual increase in task-based activation of
      the dorsal premotor cortex bilaterally. The right medial prefrontal cortex
      displayed the opposite pattern, showing initial task-based activation that
      gradually diminished with recovery. The inverse dynamics of premotor and medial
      prefrontal activity over time were found during unimanual finger-tapping with the
      affected and non-affected hand as well as during bimanual finger-tapping. These
      observations suggest that reduced premotor and increased medial prefrontal
      activity reflect an effector-independent cortical dysfunction in conversion
      paresis which gradually disappears in parallel with clinical remission of
      paresis. The results link the medial prefrontal and dorsal premotor areas to the
      generation of intentional actions. We hypothesise that an excessive 'veto' signal
      generated in medial prefrontal cortex along with decreased premotor activity
      might constitute the functional substrate of conversion disorder. This notion
      warrants further examination in a larger group of affected patients.

PMID- 29601955
TI  - The prognostic value of CHA2DS2-VASc and GRACE risk scores in patients with ACS.
AB  - OBJECTIVE: Cardiovascular diseases are the first cause of death in western
      societies. Therapeutic interventions in the individual patient should be guided
      by the so-called ischemic risk of this patient. PURPOSE: The aim of the study was
      to study the ischemic prognostic scores GRACE and CHA2DS2-VASc, in patients
      underwent angioplasty to highlight which best predicts better the ischemic risk.
      METHODS: Consecutives patients who underwent Percutaneous Coronary Intervention
      (PCI) due to Acute Coronary Disease, or elective PCI in one centre in Athens,
      Greece, where included in the study. The GRACE score and the CHA2DS2-VASc score
      were calculated. RESULTS: 667 patients participated in the study with an average
      age of 61 +/- 11 years and were followed-up for 2 years. The GRACE score and its
      predicted incidence at 3 years, was compared to the CHA2DS2-VASc score. CHA2DS2
      VASc score was able to show a marginally better prognosis of future ischemic
      events, with an AUC of 0.624 vs 0.608 of the GRACE score. CONCLUSIONS: In our
      study, The CHA2DS2-VASc score managed to predict, marginally better, the
      appearance of MACCE over GRACE, in patients with angioplasty.

PMID- 29601953
TI  - Sulcal pits and patterns in developing human brains.
AB  - Spatial distribution and specific geometric and topological patterning of early
      sulcal folds have been hypothesized to be under stronger genetic control and are
      more associated with optimal organization of cortical functional areas and their
      white matter connections, compared to later developing sulci. Several previous
      studies of sulcal pit (putative first sulcal fold) distribution and sulcal
      pattern analyses using graph structures have provided evidence of the importance
      of sulcal pits and patterns as remarkable anatomical features closely related to
      human brain function, suggesting additional insights concerning the anatomical
      and functional development of the human brain. Recently, early sulcal folding
      patterns have been observed in healthy fetuses and fetuses with brain
      abnormalities such as polymicrogyria and agenesis of corpus callosum. Graph-based
      quantitative sulcal pattern analysis has shown high sensitivity in detecting
      emerging subtle abnormalities in cerebral cortical growth in early fetal stages
      that are difficult to detect via qualitative visual assessment or using
      traditional cortical measures such as gyrification index and curvature. It has
      proven effective for characterizing genetically influenced early cortical folding
      development. Future studies will be aimed at better understanding a comprehensive
      map of spatio-temporal dynamics of fetal cortical folding in a large longitudinal
      cohort in order to examine individual clinical fetal MRIs and predict postnatal
      neurodevelopmental outcomes from early fetal life.

PMID- 29601956
TI  - The impact of financial crisis on coronary artery disease burden in Greece.
AB  - BACKGROUND: Economic crisis poses an immense threat to public health worldwide
      and has been linked to cardiovascular morbidity and mortality. Greece is facing a
      distinctive recession over the recent years. However, the exact impact on
      coronary artery disease (CAD) burden has not been adequately addressed. METHODS:
      Demographic, clinical, and angiographic data of 3895 hospitalized patients were
      retrospectively studied. Patients were classified into two groups: those before
      crisis (2006-2007, n = 1228) and those during crisis (2011-2015, n = 2667).
      RESULTS: All data before and during crisis were compared. During crisis, patients
      presented with less acute coronary syndrome (ACS - 45.5% vs. 39.9%, p < 0.001).
      Subsequently, there were more patients without CAD (23.7% vs. 35.1%, p < 0.001)
      or one-vessel disease (20.5% vs. 23%, p < 0.001). The prevalence of traditional
      risk factors decreased significantly or remained stable except obesity (26.3% vs.
      31.4%, p = 0.002). A significant increase in the examined females (23.6% vs.
      26.7%, p = 0.04) was also observed. CONCLUSIONS: The burden of CAD in Greece was
      partially affected during the financial crisis. Even though the incidence of ACS
      was decreased, more women and more patients with no- or single-vessel disease
      were referred for cardiac catheterization. In addition, the prevalence of
      traditional risk factors for CAD did not increase except obesity confirming the
      "obesity paradox." It seems that the impact of traditional risk factors for CAD
      is not an immediate process and is somewhat related to living conditions or other
      exogenous and social factors.

PMID- 29601957
TI  - Structure and electrochemistry of proteins harboring iron-sulfur clusters of
      different nuclearities. Part III. [4Fe-4S], [3Fe-4S] and [2Fe-2S] iron-sulfur
      proteins.
AB  - A systematic rationalization of the hundreds of proteins harboring iron-sulfur
      clusters and able to exhibit the most diverse biological functions is missing. In
      this picture we have already reviewed structure/electrochemistry of
      metalloproteins expressing single types of iron-sulfur centres [namely,
      {Fe(Cys)4}, {[Fe2S2](Cys)4}, {[Fe2S2](Cys)3(X)} (X = Asp, Arg, His),
      {[Fe2S2](Cys)2(His)2}, {[Fe3S4](Cys)3}, {[Fe4S4](Cys)4} and
      {[Fe4S4](SgammaCys)3(nonthiolate ligand)}] and their synthetic analogs. Recently
      we are focussing on structure/electrochemistry of metalloproteins containing iron
      sulfur centres of different nuclearities. Having started such a subject with
      proteins harboring [4Fe-4S] and [2Fe-2S] (Zanello, 2017c) as well as [4Fe-4S] and
      [3Fe-4S] (Zanello, in press) clusters, we now provide the state of art of
      proteins harboring [4Fe-4S], [3Fe-4S] and [2Fe-2S] clusters, a subject that
      resulted strictly limited to enzymes active in the respiratory Complex II.

PMID- 29601958
TI  - Polymer-free cubosomes for simultaneous bioimaging and photodynamic action of
      photosensitizers in melanoma skin cancer cells.
AB  - We designed novel polymer-free cubic bicontinuous liquid crystalline dispersions
      (cubosomes) using monoolein as molecular building block, phospholipids as
      stabilizers, propylene glycol as hydrotrope. Their kinetic stability was
      evaluated by analysing the backscattering profiles upon ageing, and the most
      stable formulation was chosen as potential photosensitizers delivery vehicle for
      photodynamic therapy (PDT) of human skin melanoma cells. Morphological and
      topological features of such formulation alternatively loaded with Chlorin e6 or
      meso-Tetraphenylporphine-Mn(III) chloride photosensitizing dyes were investigated
      by cryo-TEM, DLS, and SAXS. Bioimaging studies demonstrated that Me45 and MeWo
      cell lines effectively internalized these cubosomes formulations. Particularly,
      photodynamic activity experiments proved both the very low cytotoxicity of the
      cubosomes formulation loaded with Chlorin e6 dye in the "dark" condition, and its
      significant cytotoxic effect after photoirradiation. The toxic effect recorded
      when the photosensitizer was encapsulated within the cubosomes was shown to be
      one order of magnitude higher than that caused by the free photosensitizer. This
      is the first report of biocompatible polymer-free cubosomes for potential
      application in both PDT and bioimaging of skin malignant melanoma.

PMID- 29601959
TI  - Enhanced visible-light photocatalytic activity to volatile organic compounds
      degradation and deactivation resistance mechanism of titania confined inside a
      metal-organic framework.
AB  - Poor visible-light-driven activity and deactivation property as well as wide band
      gap of the most common TiO2 photocatalyst significantly limits its practical
      application in volatile organic compounds (VOCs) purification. In this study,
      tiny TiO2 nanoparticles incorporated into a typical metal-organic framework
      (MOF), NH2-UiO-66, with controllable TiO2 content and size, were synthesized
      based on the hard-soft acid-base (HSAB) principle and applied to VOCs
      purification. Compared to bare TiO2, the TiO2@NH2-UiO-66 composites could extend
      the optical absorption to the visible light range and accelerate the
      photogenerated electrons-holes separation, due to the excellent interface contact
      between TiO2 and NH2-UiO-66. Moreover, the abundant interconnected 3D cavities of
      the outer MOF allowed for VOCs to easily diffuse into the pores, producing a
      concentration microenvironment around the encapsulated TiO2. The TiO2@NH2-UiO-66
      composites exhibited a markedly improved photocatalytic efficiency and a good
      resistance to deactivation during the photocatalytic degradation of gaseous
      styrene under visible light illumination, which were associated with the
      synergetic effects between the TiO2 and MOF. The TiO2@NH2-UiO-66 with 5 wt% TiO2
      could efficiently mineralize styrene to CO2 to some extent companying with the
      removal ratio >99% within 600 min, whereas the removal efficiency over the bare
      TiO2 only 32.5%.

PMID- 29601960
TI  - Promising sub-100 nm tailor made hollow chitosan/poly(acrylic acid) nanocapsules
      for antibiotic therapy.
AB  - Herein, we report on the preparation of ultra-low sized (<100 nm in diameter)
      biodegradable polymeric capsules for potential applications as nanocontainers in
      antibiotic therapy. Hollow nanospheres based on the chitosan/poly(acrylic acid)
      pair are elaborated via (i) the layer-by-layer technique using gold nanoparticles
      (20 and 60 nm in size) as sacrificial templates, (ii) loading with amoxicillin, a
      betalactam antibiotic, and (iii) removal of the gold core via cyanide-assisted
      hydrolysis. Size, dispersity and concentration of the resulting nanocapsules are
      easily tuned by the nanoparticle templates, while wall thickness is controlled by
      the number of polyelectrolyte bilayers. Electrostatic interactions between the
      protonated amine groups of chitosan and the carboxyl groups of poly(acrylic acid)
      act as the driving attraction force allowing easy and fast design of robust and
      well-ordered multilayer films. Successful hydrolysis of the gold core is
      evidenced by time-dependent monitoring of the gold spectroscopic signature
      (absorbance at 519 nm and 539 nm for the gold nanoparticles with 20 and 60 nm,
      respectively). Crosslinked capsules are also prepared through crosslinking of the
      chitosan chains with glutaraldehyde. Chitosan-based nanocapsules are finally
      evidenced to be promising drug delivery vehicles of amoxicillin trihydrate with
      tuneable properties such as entrapment efficiency in the range of 62-75% and 3.5
      5.5% concerning the drug loading.

PMID- 29601961
TI  - Self-template synthesis of nickel silicate and nickel silicate/nickel composite
      nanotubes and their applications in wastewater treatment.
AB  - Hierarchical one-dimensional (1D) hollow nanostructures have attracted intense
      research attention due to their unique structures that may be capable of many
      promising applications. Here, we report a facile and effective strategy to
      prepare nickel silicate nanotubes (NiSNTs). Using this approach, mesoporous SiO2
      nanorods served as sacrificial templates for a simple hydrothermal process to
      prepare NiSNTs via a self-template route. The obtained NiSNTs preserve the
      tubular hierarchical morphology and hollow interior structures, which confer the
      NiSNTs with high surface areas and large pore volumes. These features point to
      NiSNTs as superior candidates for efficiently adsorbing heavy metal ions and
      organic dyes in wastewater. Moreover, NiSNTs can also serve as both supports and
      nickel sources, forming nickel silicate/nickel nanocomposite tubes (NiSNTs/Ni)
      via in situ reduction of NiSNTs under hydrothermal conditions. The addition of
      nickel precursors and surface pre-activation are therefore unnecessary. The
      NiSNTs/Ni exhibit efficient and recyclable catalytic properties when used for the
      reduction of 4-nitrophenol (4-NP). With a rational adaption, we believe this
      synthetic strategy can be extended to fabricate multifunctional one-dimensional
      hollow nanostructures with diverse compositions and morphologies, which may be
      useful for environmental protection, catalysis, energy and many other important
      domains.

PMID- 29601962
TI  - Improvement in lubricating properties of TritonX-100/n-C10H21OH/H2O lamellar
      liquid crystals with the amphiphilic ionic liquid 1-alkyl-3-methylimidazolium
      hexafluorophosphate.
AB  - The applications of ionic liquids (ILs)/lamellar liquid crystals (LLCs) have
      great potential in nanotribology because they could be used where conventional
      oils could not work. To clarify the lubricating mechanism, herein, ILs/LLCs
      lubricants were prepared by addition of amphiphilic 1-alkyl-3-methylimidazolium
      hexafluorophosphate (CnmimPF6, n = 8, 12) into TritonX-100/n-C10H21OH/H2O LLCs
      with different concentration. The influence of alkyl chain lengths of ILs on the
      microstructures and the tribological properties of LLCs were investigated. The
      phase structure parameters and the tribological properties of the LLCs in the
      presence of CnmimPF6 were analyzed via freeze-fracture transmission electron
      microscopy (FF-TEM), the small-angle X-ray scattering (SAXS) technique,
      oscillating reciprocating friction and wear tester. Compared with the LLCs
      without CnmimPF6, 4.5 wt% CnmimPF6 /LLCs can reduce the friction and wear of
      sliding pairs. The better lubricating property and antiwear capability of the
      CnmimPF6/LLCs may be attributed to the increasing of the interlayer thickness d
      and the decreasing of the bilayer thickness d0 in microstructures. This work
      provides a better understanding of the relationship between the microstructures
      and friction wear performances of ILs/LLCs.

PMID- 29601963
TI  - Co-Ag alloy protected by nitrogen doped carbon as highly efficient and
      chemoselective catalysts for the hydrogenation of halogenated nitrobenzenes.
AB  - The design of lower-cost alternative heterogeneous catalysts for the
      hydrogenation of halogenated nitrobenzenes using green method to synthesize the
      corresponding anilines is highly desirable. In this study, Ag was incorporated
      into the Co-MOFs during the growing process (Co-Ag(n)-MOFs), and then followed
      the carbothermal reduction process without any additional procedures, we
      synthesized a series of Co-Ag(n)@NCs. The self-supported catalysts exhibited
      excellent and stable catalytic performances for the chemoselective hydrogenation
      of halogenated nitrobenzenes without obvious dehalogenation. The Co-Ag bimetallic
      alloy nanoparticles were well-dispersed and protected from aggregation and
      leaching by the porous nitrogen doped carbon. Besides, either hydrazine hydrate
      (N2H4.H2O, generating byproducts N2 and H2O) or H2 could be used as green
      reducing agent with excellent selectivity towards synthesizing the corresponding
      anilines. And when the Co/Ag content ratio was approximate 1:1, the Co-Ag(1:1)@NC
      showed the best catalytic performance. Moreover, the Co-Ag(1:1)@NC could be
      efficiently recovered by using an external magnetic force and reused without
      obvious decrease of catalytic activity. Thus, such highly efficient, inexpensive,
      stable and magnetically recyclable catalysts could show great potentials in
      practical applications for many important reactions.

PMID- 29601965
TI  - High yield production of human invariant chain CD74 constructs fused to
      solubility-enhancing peptides and characterization of their MIF-binding
      capacities.
AB  - The HLA class II histocompatibility antigen gamma chain, also known as HLA-DR
      antigen-associated invariant chain or CD74, has been shown to be involved in many
      biological processes amongst which antigen loading and transport of MHC class II
      molecules from the endoplasmic reticulum to the Golgi complex. It is also part of
      a receptor complex for macrophage migration inhibitory factor (MIF), and
      participates in inflammatory signaling. The inhibition of MIF-CD74 complex
      formation is regarded as a potentially attractive therapeutic target in
      inflammation, cancer and immune diseases. In order to be able to produce large
      quantities of the extracellular moiety of human CD74, which has been reported to
      be unstable and protease-sensitive, different constructs were made as fusions
      with two solubility enhancers: the well-known maltose-binding domain and Fh8, a
      small protein secreted by the parasite Fasciola hepatica. The fusion proteins
      could be purified with high yields from Escherichia coli and were demonstrated to
      be active in binding to MIF. Moreover, our results strongly suggest that the MIF
      binding site is located in the sequence between the transmembrane and the
      membrane-distal trimerisation domain of CD74, and comprises at least amino acids
      113-125 of CD74.

PMID- 29601964
TI  - A systematic analysis of the expression of the anti-HIV VRC01 antibody in Pichia
      pastoris through signal peptide optimization.
AB  - Pichia pastoris (Komagataella phaffi) has been used for recombinant protein
      production for over 30 years with over 5000 proteins reported to date. However,
      yields of antibody are generally low. We have evaluated the effect of secretion
      signal peptides on the production of a broadly neutralizing antibody (VRC01) to
      increase yield. Eleven different signal peptides, including the murine IgG1
      signal peptide, were combinatorially evaluated for their effect on antibody
      titer. Strains using different combinations of signal peptides were identified
      that secreted approximately 2-7 fold higher levels of VRC01 than the previous
      best secretor, with the highest yield of 6.50 mg L-1 in shake flask expression.
      Interestingly it was determined that the highest yields were achieved when the
      murine IgG1 signal peptide was fused to the light chain, with several different
      signal peptides leading to high yield when fused to the heavy chain. Finally, we
      have evaluated the effect of using a 2A signal peptide to create a bicistronic
      vector in the attempt to reduce burden and increase transformation efficiency,
      but found it to give reduced yields compared to using two independent vectors.

PMID- 29601966
TI  - Facilitation of yeast-lethal membrane protein production by detoxifying with GFP
      tagging.
AB  - Recombinant techniques for target protein production have been rapidly
      established and widely utilised in today's biological research. Nevertheless,
      methods for membrane protein production have yet to be developed, since membrane
      proteins generally tend to be expressed at low levels, easily aggregated, and/or
      even toxic to their host cells. Here we report that a GFP-tagging technique can
      be applied for the stable production of membrane proteins that are toxic to their
      host cells when overexpressed, paving the way for future advances in membrane
      protein biochemistry and drug development.

PMID- 29601967
TI  - Tarsal coalition in paediatric patients.
AB  - Tarsal coalition is due to failure of segmentation between two or more foot bones
      during embryological development at a site where the joint cleft fails to
      develop. Depending on the nature of the tissue connecting the bones, the
      abnormality is a syndesmosis, synchondrosis, or synostosis. Although the
      coalition exists at birth, synostosis usually develops only late during growth.
      Talo-calcaneal and calcaneo-navicular coalitions account for over 90% of all
      cases of tarsal coalition. The joint at the site of the coalition is stiff. Pain
      during physical activity is the main symptom, although recurrent ankle sprain is
      another possible presenting manifestation. During the physical examination, range
      of-motion limitation at the hindfoot or midfoot should be sought, as well as
      varus or valgus malalignment of the hindfoot. Either pes planus or pes cavus may
      be seen. Calcaneo-navicular coalition may be visible on the standard radiograph,
      whereas talo-calcaneal coalition is best visualised by computed tomography or
      magnetic resonance imaging. As growth proceeds, the coalition becomes ossified
      and range-of-motion diminishes. Onset of the pain is often in the second decade
      of life or later. In patients with symptomatic tarsal coalition, the initial
      management should always consist in non-operative treatment for at least 6
      months. A consensus exists that surgery should be offered when non-operative
      treatment fails. Open resection of the coalition is the treatment of choice,
      although endoscopic resection is also an option. Sound evidence exists that
      resection of the coalition can produce favourable outcomes even in the long-term.
      Fusion should be reserved for failure of resection, extensive coalitions,
      multiple coalitions, and patients with advanced osteoarthritis.

PMID- 29601968
TI  - Update on leg fractures in paediatric patients.
AB  - Leg fractures are common and further increasing in prevalence in paediatric
      patients. The diagnosis is readily made in most cases. Choosing the best
      treatment is the main issue. Non-operative treatment is the reference standard
      for non-displaced or reducible and stable fractures but requires considerable
      expertise and close monitoring, as well as an immobilisation period that far
      exceeds 3 months in many cases. Some surgical teams therefore offer elastic
      stable intra-medullary nailing (ESIN) as an alternative to children who do not
      want to be immobilised for several months. Internal fixation is required for
      unstable or irreducible leg fractures. ESIN is often used as the first-line
      method, based on its very good risk/benefit ratio. For fractures that do not lend
      themselves to ESIN, optimal stabilisation can be achieved by choosing among the
      other available options (screw-plate fixation, rigid intra-medullary nailing or
      external fixation) on a case-by-case basis. Close monitoring during the first few
      days is crucial to ensure the early detection of compartment syndrome. The other
      complications and sequelae are non-specific.

PMID- 29601969
TI  - Concepts and challenges in the use of mesenchymal stem cells as a treatment for
      cartilage damage in the horse.
AB  - Osteoarthritis (OA), the most common form of joint disease affecting humans and
      horses, is characterized by the advance and decline of cartilage and loss of
      function of the affected joint. The progression of OA is steadily accompanied
      with biochemical events, which interfere with the cytokines and proteolytic
      enzymes responsible for progress of the disease. Recently, regenerative therapies
      have been used with an assumption that mesenchymal stem cells (MSCs) possess the
      potential to prevent the advancement of cartilage damage and potentially
      regenerate the injured tissue with an ultimate goal of preventing OA. We believe
      that despite various challenges, the use of allogenic versus autologous MSCs in
      cartilage regeneration, is a major issue which can directly or indirectly affect
      the other factors including, the timing of implantation, dose or cell numbers for
      implantation, and the source of MSCs. Current knowledge reporting some of these
      challenges that the clinicians might face in the treatment of cartilage damage in
      horses are presented. In this regard we conducted two independent studies. In the
      first study we compared donor matched bone marrow and synovial fluid - derived
      equine MSCs in vitro, and showed that the SFMSCs were similar to the BMMSCs in
      their proliferation, expression of CD29, CD44 and CD90, but, exhibited a
      significantly different chondrogenesis. Additionally, 3.2-21% of all SFMSCs were
      positive for MHC II, whereas, BMMSCs were negative. In the second study we
      observed that injection of both the autologous and allogenic SFMSCs into the
      tarsocrural joint resulted in elevated levels of total protein and total
      nucleated cell counts. Further experiments to evaluate the in vivo acute or
      chronic response to allogenic or autologous MSCs are imperative.

PMID- 29601970
TI  - Absorption of bicarbonate in sheep omasum.
AB  - Transport of bicarbonate across the isolated epithelium of sheep omasum was
      studied in vitro in Ussing chambers in combination with the pH-Stat method. The
      transport of HCO3- occurred in both directions, but Jms HCO3- was significant
      larger than Jsm. Reducing the activity of the apical Na/H exchanger by a low
      mucosal Na concentration caused a significant reduction of Jms HCO3-. Mucosal
      amiloride or short chain fatty acids (25 mmol l-1 SCFA) numerically decreased Jms
      HCO3-, but their combination (amiloride + SCFA) caused a significant reduction,
      which was also observed after addition of the carboanhydrase inhibitor
      ethoxyzolamide. Concentrations of 5 or 15 mmol.l-1 mucosal ammonia did not change
      transport rates. The obtained results indicate the importance of an undisturbed
      cytosolic pH for transcellular HCO3- transport, which is probably mediated by an
      anion exchanger in both the apical and basolateral membranes. Possible impairment
      of HCO3- transport appears to be an overlooked factor in the pathogenesis of
      displacement of the abomasum.

PMID- 29601971
TI  - A novel stellerite-based photocatalytic composite and its enhanced disinfection
      application.
AB  - The aim of this work was to prepare, characterize and evaluate the potential of
      novel ZnO/stellerite composite photocatalysts against Staphylococcus aureus (S.
      aureus). SEM/EDS studies employed to study the surface morphological properties
      revealed stellerite as the catalysts carrier played a role of dispersant for ZnO
      nanoparticles. The XRD patterns of the ZnO/stellerite indicated hexagonal crystal
      structure with 20-30 nm size. It was found that the crystallite size of
      ZnO/stellerite was much smaller as compared to pure ZnO and increased with
      increasing ZnO loading amount. The results of optical properties of
      ZnO/stellerite showed smaller band gap in contrast to pure ZnO, investigated by
      UV-vis absorption. Due to the optimum ZnO loading, the as-prepared ZnO-20
      composite had the highest BET surface area and the pore volume. Using the TG-DSC
      measurement, the high thermal stability of the product was studied for different
      temperature values. Antibacterial activity of ZnO/stellerite affected by the ZnO
      loading, concentration of samples and light conditions (under dark and UV
      irradiation conditions) was examined by disinfection of S. aureus. The as
      prepared ZnO-20 composite with 100 mg/L was found to exhibit excellent
      inactivation efficiencies (87.65% in the dark and 97.67% under UV illumination)
      towards S. aureus. Compared with pure ZnO, the obtained composite photocatalysts
      showed significantly better antibacterial performance by studying the
      disinfection kinetics of S. aureus. Thus, the present study reveals that the
      novel ZnO/stellerite shows great potential for its use in the targeted
      disinfection applications.

PMID- 29601972
TI  - Complexation of Chol-DsiRNA in place of Chol-siRNA greatly increases the duration
      of mRNA suppression by polyplexes of PLL(30)-PEG(5K) in primary murine syngeneic
      breast tumors after i.v. administration.
AB  - RNA interference has tremendous potential for cancer therapy but is limited by
      the insufficient potency of RNAi molecules after i.v. administration. We
      previously found that complexation with PLL(30)-PEG(5K) greatly increases the
      potency of 3'-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic
      4T1 breast tumors after i.v. administration but mRNA suppression decreases 24 h
      after the final dose. We hypothesized that complexation of cholesterol-modified
      Dicer-substrate siRNA (Chol-DsiRNA) in place of Chol-siRNA can increase the
      potency and duration of suppression by polyplexes of PLL(30)-PEG(5K) in solid
      tumors. We found that replacing Chol-siRNA with Chol-DsiRNA increased polyplex
      loading and nuclease protection, suppressed stably expressed luciferase to the
      same extent in primary murine 4T1-Luc breast tumors under the current dosage
      regimen, but maintained suppression ~72 h after the final dose. The kinetics of
      suppression in 4T1-Luc over 72 h, however, were similar between DsiLuc and siLuc
      after electroporation and between polyplexes of Chol-DsiLuc and Chol-siLuc after
      transfection, suggesting that Chol-DsiRNA polyplexes increase the duration of
      mRNA suppression through differences in polyplex activities in vivo. Thus,
      replacing Chol-siRNA with Chol-DsiRNA may significantly increase the duration of
      mRNA suppression by polyplexes of PLL(30)-PEG(5K) and possibly other PEGylated
      polycationic polymers in primary tumors and metastases after i.v. administration.

PMID- 29601973
TI  - Evaluation of a new dispersion technique for assessing triboelectric charging of
      powders.
AB  - In a number of applications, especially in pharmaceutical drug development, there
      is often a very small powder quantity available for evaluating the
      manufacturability of new drugs. However, it is highly desirable to be able to
      quickly evaluate processing issues, and where possible using the smallest powder
      quantity. In the present work, a proprietary commercial powder dispersion device
      (the disperser of Malvern(c) Morphologi G3) is adapted to evaluate the
      triboelectric charging tendency. A very small powder quantity (as small as 0.1
      mg) is dispersed by a pressure pulse of compressed gas such as air or nitrogen.
      This causes the particles to become air borne and collide with the containing
      walls, resulting in dispersion and leading to triboelectric charge transfer
      between the particles and the walls. In this work, the charging propensity of a
      number of materials is evaluated and the effect of particle surface functional
      groups on the tribo-electric charge transfer is analysed. Model materials with a
      well-defined shape (glass ballotini) but with different silane groups deposited
      on their surfaces as well as a number of organic crystalline particles (such as
      aspirin, alpha-lactose monohydrate and paracetamol) are tested. Following
      dispersion the particles move immediately to a Faraday cup placed directly
      underneath the disperser. Therefore, particle charge is measured with no decay.
      The method can differentiate charging of different polymorphs of the same
      material, different silane groups on the surfaces of glass ballotini and
      different crystal morphologies obtained from crystallisation from various
      solvents.

PMID- 29601974
TI  - Preparation of sustained release capsules by electrostatic dry powder coating,
      using traditional dip coating as reference.
AB  - Lately, a great deal of attention is being paid to capsule coating, since the
      coat protects active pharmaceutical ingredients (APIs) from damage, as is in the
      case of tablet and pellet. However, moisture and heat sensitivity of gelatin
      shells make it challenging to coat capsules using the conventional aqueous
      coating techniques. In an effort to overcome this challenge, the present study
      aims to coat capsules using two different coating techniques: electrostatic dry
      powder coating (EDPC) and dip coating (DC). Both capsule coatings and free films
      were prepared by these two coating techniques, and the effects of coating
      formulations and processing conditions on the film quality were investigated. The
      corresponding drug in vitro release and mechanisms were characterized and
      compared. The results of dissolution tests demonstrated that the drug release
      behavior of both EDPC and DC coated capsules could be optimized to a sustained
      release of 24 h, following the Fick's diffusion law. The results of this study
      suggest that EDPC method is better than DC method for coating capsules, with
      respect to the higher production efficiency and better stability, indicating that
      this dry coating technology has promised in gelatin capsule coating applications.

PMID- 29601975
TI  - Application of a simple desolvation method to increase the formation yield,
      physical stability and hydrophobic drug encapsulation capacity of chitosan-based
      nanoparticles.
AB  - As one of the classical nano drug carriers, chitosan-based nanoparticles (CsNps)
      are getting increasing attentions for their non-toxicity, biocompatibility and
      biodegradability. The ionotropic gelation is the most favorable method for CsNps
      preparation, while it's beset by some issues, i.e. low particle formation yield,
      poor physical stability and low hydrophobic drug loading capacity. To solve these
      problems, a simple desolvation method was attempted in this study for CsNps
      preparation. Using this method, an increased formation yield of CsNps (about
      100%) could be obtained, and after diluting the particles by various buffers (PBS
      7.0, 7.4 and 8.0, DMEM medium and 1640 medium), an improved stability in diameter
      could be observed. The drug loading results showed paclitaxel loading efficiency
      of 9.8% could be obtained when the ratio of paclitaxel to Cs was set at 0.2,
      higher than the ionotropic gelation method (0.43%). The particles formation
      mechanisms were studied by the molecular dynamics simulation, and the results
      showed the Lennard-Jones interaction of Cs-Cs, which could be adjusted by the pH
      value of system, played a great role in formation of particles with the
      desolvation method. This study provided an alternative preparation technology for
      CsNps with high process yield, physical stability and hydrophobic drug
      encapsulation capacity.

PMID- 29601976
TI  - Advances in drug delivery related biosensors and medical devices.

PMID- 29601978
TI  - Prolactin regulatory element-binding (PREB) protein regulates hepatic glucose
      homeostasis.
AB  - Prolactin regulatory element-binding (PREB) protein is a transcription factor
      that regulates prolactin (PRL) gene expression. PRL, also known as luteotropic
      hormone or luteotropin, is well known for its role in producing milk. However,
      the role of PREB, in terms of hepatic glucose metabolism, is not well elucidated.
      Here, we observed expression of Preb in the mouse liver, in connection with
      glucose homeostasis. Morevoer, Preb was downregulated in db/db, ob/ob and high
      fat diet-induced obese (DIO) mice, concurrent with upregulation of the liver
      genes glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase-1 (Pck).
      Administration of adenovirus-Preb (Ad-Preb) to db/db, ob/ob, and DIO mice
      diminished glucose, insulin, and pyruvate tolerance, which analogously, were
      impaired in normal (C57BL/6) mice knocked down for Preb, via infection with Ad
      shPreb (anti-Preb RNA), indicating Preb to be a negative regulator of liver
      gluconeogenic genes. We further demonstrate that Preb negatively influences
      gluconeogenic gene expression, by directly binding to their promoters at a
      prolactin core-binding element (PCBE). A better understanding of Preb gene
      expression, during the pathogenesis of hepatic insulin resistance, could
      ultimately provide new avenues for therapies for metabolic syndrome, obesity, and
      type-2 diabetes mellitus, disorders whose worldwide incidences are increasing
      drastically.

PMID- 29601977
TI  - SURF1 knockout cloned pigs: Early onset of a severe lethal phenotype.
AB  - Leigh syndrome (LS) associated with cytochrome c oxidase (COX) deficiency is an
      early onset, fatal mitochondrial encephalopathy, leading to multiple neurological
      failure and eventually death, usually in the first decade of life. Mutations in
      SURF1, a nuclear gene encoding a mitochondrial protein involved in COX assembly,
      are among the most common causes of LS. LSSURF1 patients display severe, isolated
      COX deficiency in all tissues, including cultured fibroblasts and skeletal
      muscle. Recombinant, constitutive SURF1-/- mice show diffuse COX deficiency, but
      fail to recapitulate the severity of the human clinical phenotype. Pigs are an
      attractive alternative model for human diseases, because of their size, as well
      as metabolic, physiological and genetic similarity to humans. Here, we determined
      the complete sequence of the swine SURF1 gene, disrupted it in pig primary
      fibroblast cell lines using both TALENs and CRISPR/Cas9 genome editing systems,
      before finally generating SURF1-/- and SURF1-/+ pigs by Somatic Cell Nuclear
      Transfer (SCNT). SURF1-/- pigs were characterized by failure to thrive, muscle
      weakness and highly reduced life span with elevated perinatal mortality, compared
      to heterozygous SURF1-/+ and wild type littermates. Surprisingly, no obvious COX
      deficiency was detected in SURF1-/- tissues, although histochemical analysis
      revealed the presence of COX deficiency in jejunum villi and total mRNA
      sequencing (RNAseq) showed that several COX subunit-encoding genes were
      significantly down-regulated in SURF1-/- skeletal muscles. In addition,
      neuropathological findings, indicated a delay in central nervous system
      development of newborn SURF1-/- piglets. Our results suggest a broader role of
      sSURF1 in mitochondrial bioenergetics.

PMID- 29601979
TI  - Ethnobotanical study of medicinal plants used by indigenous people in and around
      Dirre Sheikh Hussein heritage site of South-eastern Ethiopia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The uses of medicinal plants have a long history
      and become important sources of the health cares in Ethiopia. These medicinal
      plants and their associated indigenous knowledge are being seriously depleted due
      to rapid change in environment and socioeconomic conditions of the country.
      However, as to the knowledge of the present researchers, limited studies have
      been done to identify these medicinal plants and to preserve the communities'
      indigenous knowledge on these plants. THE AIM OF THE STUDY: This study aimed at
      assessing and documenting traditional medicinal plant species, mode of
      preparation and delivery, and parts used in and around Dirre Sheikh Hussein
      heritage site of South-eastern Ethiopia. The study was also meant to explore
      related indigenous knowledge of the communities on the utilization of medicinal
      plants. MATERIAL AND METHODS: The data were collected using household survey, in
      depth interviews of key informants, focus group discussion and field observation.
      The number of informants involved in the survey was 194 (one hundred ninety
      four). RESULTS: A total of 87 medicinal plants belonging to 77 genera and 51
      families were identified. These medicinal plants were comprised of shrubs (33%),
      trees (31%), herbs (29%) and climbers (7%). Of the total number of medicinal
      plants found out in the study, 43 were used to treat human diseases, 8 were used
      to cure animal diseases and 36 were used to treat both human and live stock
      ailments. Of the identified plant species, about 83% species were proved that
      they are commonly known and used elsewhere whereas, the uses of remainder ones
      are limited to the study area. Most of the medicinal plants (60%) were sourced
      from the forest and the rest were found from both the forest garden. The study
      also revealed that leaves were the most frequently mentioned (36%) plant part
      used in preparing remedies. Crushing (20%) and oral route of administration (59%)
      were commonly mentioned mode of preparation and administration, respectively The
      study also indicated that peoples' perception and cultural beliefs had
      significant influence on their preference of source of health care, whereas
      religion was found to have no association with the health seeking behavior.
      CONCLUSIONS: This study revealed that varieties of plant species are playing
      important role for treating different human and livestock diseases in the study
      area, and traditional healers have accumulated wealth indigenous knowledge on
      usage of plant medicine inherited through generation. Besides, the therapeutic
      use of the documented plants will provide basic data for further research that
      focus on pharmacological studies and the conservation of the most important
      medicinal plants.

PMID- 29601980
TI  - Pharmacological effect of prohibited combination pair Panax ginseng and Veratrum
      nigrum on colorectal metastasis in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The pharmacological effect derived from herb-herb
      interaction is important to constitute the prescription especially in traditional
      oriental medicine. The relationship of two medicinal herbs is called "couplet
      medicinals" which is used in pair for the purpose of enhancing the therapeutic
      effect, reducing the toxic effect or the adverse effect. The "Eighteen
      Incompatible Medicaments" constitute one of the contents in the incompatibility
      of traditional oriental drugs in a prescription. Among the "Eighteen Incompatible
      Medicaments", the roots and rhizomes of Veratrum nigrum (VN), is incompatible
      with the roots and rhizomes of Panax ginseng (PG). However, definite evidences of
      adverse effect by these combinations has yet to be reported. MATERIALS AND
      METHODS: The aim of the present study was to investigate the effects of ethanol
      extracts of PG, VN, and their combination (P + V) on the metastatic ability of
      colorectal cancer (CRC) cells using WST assay, flow cytometry, western blot
      analysis, real-time RT-PCR, immunofluorescence, migration assay, invasion assay,
      zymography, and an in vivo experiment with a lung-metastasis mouse model.
      RESULTS: The PG extract decreased cell proliferation by inducing cell cycle
      arrest and apoptosis of CRC cells. In addition, PG inhibited metastatic abilities
      of CRC cells including Epithelial-Mesenchymal Transition, migration, and
      invasion. Additionally, the PG extract suppressed lung metastasis of the CRC
      cells in the mouse model. However, the P + V extract exhibited weaker anti
      proliferative and anti-metastatic effects than PG alone. CONCLUSION: Based on
      these results, the P + V couplet medicinal attenuates the anti-metastatic effects
      of PG, both in vitro and in vivo.

PMID- 29601981
TI  - The role of oxytocin in implicit personal space regulation: An fMRI study.
AB  - Personal space, defined as the distance individuals choose to maintain between
      themselves and others, is an indicator of affiliation and closeness. Most
      paradigms that measure personal space preferences involve explicit choice and
      therefore fail to examine the implicit aspects of such preferences. In the
      current study, we sought to investigate an implicit form of interpersonal space
      that is more closely related to real-life situations involving affiliation. We
      studied the effects of oxytocin (OT) on neural networks that involve affiliation
      and tested the impact on personal space preferences. In a double-blind placebo
      controlled study, we asked participants to choose between two rooms that differed
      only in the distances between two stimuli. The stimuli were either social stimuli
      (two chairs) or non-social stimuli (table and plant). The behavioral results
      showed that OT caused participants to choose a closer space in social blocks but
      did not affect their choices in non-social blocks. Imaging results revealed an
      interaction between stimulus and treatment (OT/PL) in the dorsal striatum, an
      area that is related to approach motivation and is part of the reward circuitry.
      Specifically, OT increased activity in the dorsal striatum in the social blocks
      and decreased this activity in the non-social blocks. The results of the study
      strengthen the social salience theory regarding OT, indicating that OT does not
      uniformly affect all social responses and that context has a determining impact
      on our behavior.

PMID- 29601982
TI  - Quantitation of peptides from non-invasive skin tapings using isotope dilution
      and tandem mass spectrometry.
AB  - Previous work from our laboratories utilized a novel skin taping method and mass
      spectrometry-based proteomics to discover clinical biomarkers of skin conditions;
      these included atopic dermatitis, Staphylococcus aureus colonization, and eczema
      herpeticum. While suitable for discovery purposes, semi-quantitative proteomics
      is generally time-consuming and expensive. Furthermore, depending on the method
      used, discovery-based proteomics can result in high variation and inadequate
      sensitivity to detect low abundant peptides. Therefore, we strove to develop a
      rapid, sensitive, and reproducible method to quantitate disease-related proteins
      from skin tapings. We utilized isotopically-labeled peptides and tandem mass
      spectrometry to obtain absolute quantitation values on 14 peptides from 7
      proteins; these proteins had shown previous importance in skin disease. The
      method demonstrated good reproducibility, dynamic range, and linearity (R2 >
      0.993) when n = 3 standards were analyzed across 0.05-2.5 pmol. The method was
      used to determine if differences exist between skin proteins in a small group of
      atopic versus non-atopic individuals (n = 12). While only minimal differences
      were found, peptides were detected in all samples and exhibited good correlation
      between peptides for 5 of the 7 proteins (R2 = 0.71-0.98). This method can be
      applied to larger cohorts to further establish the relationships of these
      proteins to skin disease.

PMID- 29601983
TI  - Corneal lymphangiogenesis facilitates ocular surface inflammation and cell
      trafficking in dry eye disease.
AB  - PURPOSE: While the normal cornea has limited innervation by the lymphatic system,
      chronic immune-inflammatory disorders such as dry eye (DE) can induce
      lymphangiogenesis in the ocular surface. Using a conditional knock-down murine
      model, Lyve-1Cre;VEGFR2flox mice, this study investigated the role of
      lymphangiogenesis in the pathophysiology of DE. METHODS: DE was induced in both
      wild type (WT) B6 and Lyve-1Cre;VEGFR2flox mice. Tissue immunostaining and
      volumetric gross measurements were used to assess changes in the ocular surface,
      skin, and lymph nodes (LNs). The expression of lymphangiogenic factors (TNF
      alpha, IL-6/-8/-12/-17, VEGF-C/-D, IFN-gamma, VEGFR-2/-3, Lyve-1, and podoplanin)
      and the frequency of immune cells (CD4, CD11b, and CD207) on the ocular surface
      and lacrimal glands were quantified by real-time polymerase chain reaction and
      flow cytometry. RESULTS: Compared to WT mice, there were fewer lymphatic vessels
      and a reduction in lymphangiogenic markers in the ocular surface and skin of Lyve
      1Cre;VEGFR2flox mice. After DE induction, mRNA levels of TNF-alpha, IL-8, and IFN
      gamma were significantly reduced in Lyve-1Cre;VEGFR2flox mice compared to WT mice
      (p < .01). Surprisingly, the LNs from Lyve-1Cre;VEGFR2flox mice with DE were
      significantly smaller and populated by fewer dendritic cells and effector T cells
      than those from WT mice (p < .001). Furthermore, immunostaining showed corneal
      nerves in the DE-induced Lyve-1Cre;VEGFR2flox mice were notably intact like in
      the naive condition. CONCLUSIONS: Inhibition of lymphangiogenesis in the cornea
      effectively attenuates not only the inflammatory response including trafficking
      of immune cells but also preserves corneal nerves under desiccating stress.
      Corneal lymphangiogenesis might be a contributing factor in deterioration on the
      ocular surface homeostasis.

PMID- 29601984
TI  - Piriformospora indica, an excellent system for heavy metal sequestration and
      amelioration of oxidative stress and DNA damage in Cassia angustifolia Vahl under
      copper stress.
AB  - Present investigation reveals copper induced phytotoxicity, oxidative stress and
      DNA damage in Cassia angustifolia Vahl and its amelioration by employing a
      symbiotic fungus, Piriformospora indica. Seeds were germinated on Knop's medium
      containing five Cu levels (0, 1, 10, 50, 100 and 200 mg L-1), with and without P.
      indica. Colonization with P. indica significantly (P < 0.05) ameliorated Cu
      induced oxidative stress. However, maximum amelioration was observed at 50 mg L-1
      Cu with P. indica. Atomic absorption spectroscopy revealed that P. indica
      colonization significantly inhibited Cu accumulation in shoots. Maximum decline
      in Cu accumulation in shoots was observed at 50 mg L-1 (27.27%) with P. indica
      over Cu alone. Besides, P. indica colonized seedlings stored 16.86% higher Cu in
      roots as compared to Cu alone at 200 mg L-1. Similarly, maximum proline
      accumulation increased up to 19.32% over Cu alone at 50 mg L-1 Cu with P. indica.
      Significant elevation in antioxidant enzyme levels of superoxide dismutase,
      catalase, ascorbate peroxidase, guaiacol peroxidase and glutathione reductase was
      seen with P. indica. Contrary to increase in antioxidant level, toxic parameters
      such as lipid peroxidation and hydrogen peroxide decreased significantly with P.
      indica. Maximum decline in lipid peroxidation (13.76%) and hydrogen peroxide
      (18.58%) was observed at 50 mg L-1 with P. indica over Cu alone. P. indica
      significantly reduced DNA damage as well as changed the protein profile in C.
      angustifolia seedlings. Thus, P. indica proved to be an excellent system to
      alleviate Cu induced oxidative stress and might be useful as a phytostabilization
      tool.

PMID- 29601985
TI  - Mechanical characterization and numerical simulation of a subcutaneous
      implantable 3D printed cell encapsulation system.
AB  - Cell transplantation in bioengineered scaffolds and encapsulation systems has
      shown great promise in regenerative medicine. Depending on the site of
      implantation, type of cells and their expected function, these systems are
      designed to provide cells with a physiological-like environment while providing
      mechanical support and promoting long-term viability and function of the graft. A
      minimally invasive 3D printed system termed neovascularized implantable cell
      homing and encapsulation (NICHE) was developed in polylactic acid for
      subcutaneous transplantation of endocrine cells, including pancreatic islets. The
      suitability of the NICHE for long term in vivo deployment is investigated by
      assessing mechanical behavior of both fresh devices under simulated subcutaneous
      conditions and NICHE retrieved from subcutaneous implantation in pigs. Both
      experimental and numerical studies were performed with a focus on validating the
      constitutive material model used in the numerical analysis for accuracy and
      reliability. Notably, homogeneous isotropic constitutive material model
      calibrated by means of uniaxial testing well suited experimental results. The
      results highlight the long term durability for in vivo applications and the
      potential applicability of the model to predict the mechanical behavior of
      similar devices in various physiological settings.

PMID- 29601986
TI  - A study of the reproducibility and reliability of the musculo-articular stiffness
      of the ankle joint.
AB  - The objective of this work was to evaluate the reproducibility, reliability and
      usefulness of the musculo-articular stiffness (MAS) of the ankle joint, measuring
      it by the free vibration technique. Seventeen (nine males and eight females)
      healthy university students were included in the study. Force (f), MAS (k) and
      unitary MAS (ku) (defined as the ratio between the value of stiffness k obtained
      in the test (absolute terms) and the value of force (f)) were obtained. A test
      retest protocol was designed and performed on the same day to determine the short
      term reproducibility of f, k and ku. Short-term reproducibility of k and ku on 1
      day in absolute terms (< 7% Coefficient of Variation (CV)) and relative
      reproducibility (Intraclass Correlation Coefficient (ICC) and Pearson >= 0.97)
      for both feet were obtained. The reliability of k and ku in absolute terms (< 9%
      CV) and in relative terms (ICC and Pearson >=0.93) based on repeating the
      protocol for 1 week was analysed for both feet. To analyse the usefulness, the
      Effect Size (ES) ratio = "Trivial" for all variables (for 1 day and 1 week) and
      the Smallest Worthwhile Change (SWC) ratio (Typical Error (TE)< SWC) = "GOOD" for
      k and ku (1 day and 1 week) were considered. The Minimal Difference needed to be
      considered "real" (MD) for ku ? 3.5% (1 day); ku? 8.5% (1 week) (p < 0.05) was
      obtained. The statistical analysis carried out displayed the high
      reproducibility, reliability and usefulness of the MAS test, which was more
      consistent with ku than k. Therefore, the unitary stiffness (ku) proven to be
      representative of the mechanical response of the ankle joint obtained by free
      vibration techniques, which allows comparison between different subjects.

PMID- 29601987
TI  - Multi-axial damage and failure of medical grade carbon fibre reinforced PEEK
      laminates: Experimental testing and computational modelling.
AB  - Orthopaedic devices using unidirectional carbon fibre reinforced poly-ether-ether
      ketone (PEEK) laminates potentially offer several benefits over metallic implants
      including: anisotropic material properties; radiolucency and strength to weight
      ratio. However, despite FDA clearance of PEEK-OPTIMATM Ultra-Reinforced, no
      investigation of the mechanical properties or failure mechanisms of a medical
      grade unidirectional laminate material has been published to date, thus hindering
      the development of first-generation laminated orthopaedic devices. This study
      presents the first investigation of the mechanical behaviour and failure
      mechanisms of PEEK-OPTIMATM Ultra-Reinforced. The following multi-axial suite of
      experimental tests are presented: 0 degrees  and 90 degrees  tension and
      compression, in-plane shear, mode I and mode II fracture toughness, compression
      of +/-45 degrees  laminates and flexure of 0 degrees , 90 degrees  and +/-45
      degrees  laminates. Three damage mechanisms are uncovered: (1) inter-laminar
      delamination, (2) intra-laminar cracking and (3) anisotropic plasticity. A
      computational damage and failure model that incorporates all three damage
      mechanisms is developed. The model accurately predicts the complex multi-mode
      failure mechanisms observed experimentally. The ability of a model to predict
      diverse damage mechanisms under multiple loading directions conditions is
      critical for the safe design of fibre reinforced laminated orthopaedic devices
      subjected to complex physiological loading conditions.

PMID- 29601988
TI  - Oxide ceramic femoral heads contribute to the oxidation of polyethylene liners in
      artificial hip joints.
AB  - Experimental evidence demonstrates that a loss of stoichiometry at the surface of
      oxide bioceramic femoral heads enhances the oxidation rate of polyethylene
      acetabular liners in artificial hip joints. Contradicting the common notion that
      ceramics are bioinert, three independent experiments confirmed substantial
      chemical interactions between the ceramic femoral heads and their polyethylene
      counterparts. The experiments reported herein included hydrothermal tests,
      frictional tests, and hip-simulator experiments. It was discovered that oxide and
      non-oxide femoral heads differently affected the oxidation processes at the
      surface of the polyethylene liners, all other testing parameters being equal.
      Analytical data from X-ray photoelectron (XPS), cathodoluminescence (CL), Fourier
      transform infrared (FTIR), and Raman spectroscopies unequivocally and
      consistently showed that the oxidation rate of polyethylene liners was greater
      when coupled with oxide as opposed to non-oxide ceramic heads. XPS analyses of O
      Al-O bond fractions at the surface of a zirconia-toughened alumina (ZTA) short
      term (20 months in vivo) femoral heads retrieval showed a ~50% reduction in favor
      of oxygen vacancy O-Al-VO and hydroxylated Al-O-H bonds. Off-stoichiometry drifts
      were confirmed in vitro under both static and dynamic conditions. They triggered
      oxidation and tangibly affected an advanced highly cross-linked sequentially
      irradiated and annealed ultra-high molecular weight polyethylene (UHMWPE) liner
      (increase in oxidation index up to DeltaOI~1.2 after 5 * 105 cycles under dynamic
      swing conditions). Second-generation UHMWPE liners infused with vitamin E were
      also affected by the free flow of oxygen from the oxide femoral heads, although
      to a lesser extent. The fundamental findings of this study, which were also
      confirmed on retrievals, call for revised standards in material design and
      testing. Adopting these new criteria will provide an improved understanding of
      the importance of off-stoichiometry at the head/liner interface and may lead to
      significant extensions in artificial joint lifetimes.

PMID- 29601989
TI  - A hybrid model based on neural networks for biomedical relation extraction.
AB  - Biomedical relation extraction can automatically extract high-quality biomedical
      relations from biomedical texts, which is a vital step for the mining of
      biomedical knowledge hidden in the literature. Recurrent neural networks (RNNs)
      and convolutional neural networks (CNNs) are two major neural network models for
      biomedical relation extraction. Neural network-based methods for biomedical
      relation extraction typically focus on the sentence sequence and employ RNNs or
      CNNs to learn the latent features from sentence sequences separately. However,
      RNNs and CNNs have their own advantages for biomedical relation extraction.
      Combining RNNs and CNNs may improve biomedical relation extraction. In this
      paper, we present a hybrid model for the extraction of biomedical relations that
      combines RNNs and CNNs. First, the shortest dependency path (SDP) is generated
      based on the dependency graph of the candidate sentence. To make full use of the
      SDP, we divide the SDP into a dependency word sequence and a relation sequence.
      Then, RNNs and CNNs are employed to automatically learn the features from the
      sentence sequence and the dependency sequences, respectively. Finally, the output
      features of the RNNs and CNNs are combined to detect and extract biomedical
      relations. We evaluate our hybrid model using five public (protein-protein
      interaction) PPI corpora and a (drug-drug interaction) DDI corpus. The
      experimental results suggest that the advantages of RNNs and CNNs in biomedical
      relation extraction are complementary. Combining RNNs and CNNs can effectively
      boost biomedical relation extraction performance.

PMID- 29601990
TI  - Design, synthesis and antitubercular evaluation of benzothiazinones containing a
      piperidine moiety.
AB  - We herein report the design and synthesis of benzothiazinones containing a
      piperidine moiety as new antitubercular agents based on the structure feature of
      IMB-ZR-1 discovered in our lab. Some of them were found to have good in vitro
      activity (MIC < 1 MUg/mL) against drug-susceptible Mycobacterium tuberculosis
      H37RV strain. After two set of modifications, compound 2i were found to display
      comparable in vitro anti-TB activity (MIC < 0.016 MUg/mL) to PBTZ169 against drug
      sensitive and resistant mycobacterium tuberculosis strains. Compound 2i also
      showed acceptable PK profiles. Studies to determine PK profiles in lung and in
      vivo efficacy of 2i are currently under way.

PMID- 29601991
TI  - Discovery of novel quinazolinone derivatives as high potent and selective
      PI3Kdelta and PI3Kdelta/gamma inhibitors.
AB  - PI3Kdelta and PI3Kgamma regulate immune cell signaling. Selective PI3Kdelta or
      PI3Kgamma inhibitors and dual PI3Kdelta/gamma inhibitors have the potential for
      the treatment of immune cell-mediated diseases and hematological malignancies.
      Based on the quinazolinone pharmacophore, we used a pyrazolo[3,4-d]pyrimidin-4
      amine portion as the hinge region binding moiety, an aromatic or a heteroaromatic
      substituent at the 3-position of the pyrazolo[3,4-d]pyrimidine core as the
      affinity element, and designed novel 2-tolyl and 2,6-dimethylphenyl quinazolinone
      derivatives as potential PI3Kdelta inhibitors. Most of these compounds displayed
      high inhibitory rates (89-97%) against PI3Kdelta at the concentration of 1 MUM,
      with the IC50 values of 8.4 nM-106 nM. Among the 3-(2,6
      dimethylphenyl)quinazolinone series, the introduction of an indol-5-yl
      substituent at the pyrazolo[3,4-d]pyrimidine 3-position led to a potent and
      selective PI3Kdelta (IC50 = 8.6 nM) inhibitor 10d, that was more than 3630-fold,
      390-fold and 40-fold selective for PI3Kdelta over PI3Kalpha, beta and gamma,
      while the substitution with a 3,4-dimethoxyphenyl resulted in a potent and
      selective dual PI3Kdelta/gamma inhibitor 10e with IC50 values of 8.4 nM and 62 nM
      against PI3Kdelta and PI3Kgamma, respectively. Compound 10e was also more than
      1400-fold, 820-fold selective for PI3Kdelta over PI3Kalpha and PI3Kbeta. In
      agreement with their remarkable PI3Kdelta inhibitory activity, compounds 10d and
      10e showed high antiproliferative activity against human B-cell SU-DHL-6 cells.
      Moreover, the dual PI3Kdelta/gamma inhibitor 10e had reasonable pharmacokinetic
      profiles with a good plasma exposure, low clearance, low volume distribution, and
      an acceptable oral bioavailability of 34.9%.

PMID- 29601992
TI  - Cloning and functional characterization of thioredoxin genes from large yellow
      croaker Larimichthys crocea.
AB  - Thioredoxin(Trx)with a redox-active disulfide/dithiol in the active site, is an
      ubiquitous disulfide reductase majorly responsible for maintaining the balance of
      reactive oxygen species. In this study, the complete thioredoxin-like protein 1
      (designated as LcTrx) was cloned from large yellow croaker Larimichthys crocea
      through rapid amplification of cDNA ends. The full-length cDNA of LcTrx was 1295
      bp in length containing a 131 bp 5' untranslated region (UTR) ,a 3'UTR of 294bp
      with a poly (A) tail, and an 870 bp open reading frame (ORF) encoding a
      polypeptide of 289 amino acids. Protein sequence analysis revealed that LcTrx
      contains the evolutionarily conserved redox motif CRPC (Cys-Arg-Pro-Cys-).
      Multiple alignments revealed that LcTrx is highly identical to Trx from other
      organisms, especially in the CRPC motifs. The recombinant LcTrx showed obvious
      insulin reduction activity in vitro. The LcTrx transcripts were constitutively
      expressed in all examined tissues with the highest levels found in the muscles
      and the lowest in the head kidney. Results of Vibrio parahaemolyticus infection
      experiment showed that the expression levels of LcTrx were tissue and time
      dependent. In the liver and kidney, LcTrx was down-regulated both at 12 h and 48
      h post-infection. In contrast, LcTrx showed induced expression in the spleen and
      head kidney at same post-infection time points. The different responses to
      pathogen stimulation indicated the diversified physiological function of LcTrx in
      the four examined tissues.

PMID- 29601993
TI  - Antimicrobial activity of a serine proteinase inhibitor SPIPm5 from the black
      tiger shrimp Penaeus monodon.
AB  - A two-domain Kazal-type serine proteinase inhibitor, SPIPm5, from Penaeus monodon
      was studied. Its transcript was expressed in all tissues tested including the
      hemocytes, stomach, gill, lymphoid organ, muscle, intestine and heart albeit less
      in hepatopancreas and eyestalk. The expression of SPIPm5 gene was also up
      regulated by heat stress, white spot syndrome virus (WSSV) infection and yellow
      head virus (YHV) infection. Injection of recombinant rSPIPm5 protein into normal
      shrimp to mimic heat stress condition did not have or had little stimulating
      effect on the expression of other immune genes: crustinPm1, penaeidin3,
      penaeidin5, Hsp70, SPIPm2 and SPIPm5. Like some other proteinase inhibitors, the
      rSPIPm5 could inhibit the hemolymph proPO activity. In survival experiments, the
      rSPIPm5 could prolong the life of WSSV-infected shrimp similar to the effect of
      heat stress. The rSPIPm5 also helped the YHV-, Vibrio harveyi- and V.
      parahaemolyticus-infected shrimp survive longer. The increased endurance against
      microbial infection was due to the inhibitory effects presumably activated by
      rSPIPm5 on viral replication and bacterial growth but not the expression of
      antimicrobial peptides. Therefore, the SPIPm5 plays an important role in shrimp
      innate immunity against the viral and bacterial infection.

PMID- 29601994
TI  - C-terminal domain of WSSV VP37 is responsible for shrimp haemocytes binding which
      can be inhibited by sulfated galactan.
AB  - Viral envelope proteins play an important role in facilitating the attachment of
      viruses to the surface of host cells. Here, we investigated the binding of White
      Spot Syndrome Virus (WSSV) VP37 to haemocytes of whiteleg shrimp, Litopenaeus
      vannamei. Three versions of recombinant VP37 proteins, including full length VP37
      (VP37(1-281)), C-terminal domain VP37 (VP37(111-281)) and C-terminal domain
      disrupted VP37 (VP37(1-250)) were individually expressed and tested for their
      haemocytes binding ability. Through an ELISA-based binding assay, we found that
      VP37(111-281) bound to shrimp haemocytes in a similar way to VP37(1-281), while
      VP37(1-250) exhibited a significantly weaker binding. This suggests that the C
      terminal domain of VP37 is required for the binding of VP37 to shrimp haemocytes.
      Furthermore, we found that the binding of VP37 to shrimp haemocytes was impaired
      by pre-incubation of VP37 with sulfated galactan (SG), a sulfated polysaccharide
      derived from red seaweed (Gracilaria fisheri). Previously, it has been shown that
      a type of sulfated polysaccharide, heparin, is also present in L. vannamei. To
      investigate the role of heparin as a receptor for VP37, the binding of VP37 to
      porcine heparin, whose structure is similar to that found in L.vannamei, was
      investigated in a Surface Plasmon Resonance (SPR) system. The results showed that
      VP37 bound strongly to heparin with binding affinity (KD) of 1.0 MUM and the
      binding was significantly blocked by SG. These findings have lead us to propose
      that the attachment of WSSV might be mediated by the interaction between VP37 and
      a heparin-like molecule presented on the shrimp cells.

PMID- 29601995
TI  - Effect of chromium on granule-based anammox processes.
AB  - In this study, the feasibility of application of anaerobic ammonium oxidation
      (anammox) to teat wastewater containing chromium was assessed. Anammox granule
      activity decreased with increasing Cr(VI) concentration and pre-exposure time in
      batch tests, and the 50% inhibition concentration of Cr(VI) on anammox biomass
      was 296.5 mg L-1. Approximately 93.9% chromium was absorbed by loosely bound
      extracellular polymeric substances and tightly bound-extracellular polymeric
      substances when less than 60 mg L-1 Cr(VI) was added. During long-term operation
      in up-flow anaerobic sludge blanket reactor, significant inhibitory effects
      anammox performance were observed for Cr(VI) concentrations up to 2 mg L-1. The
      nitrogen removal rate (NRR) rapidly decreased to 1.49 +/- 0.89 kg N m-3 d-1,
      whereas the NRR was 11.37 +/- 1.30 kg N m-3 d-1 in a control reactor. Compared
      with initial levels, specific anammox granule activity was 22%. The tolerance of
      the anammox process to Cr(VI) can be enhanced after a long-term adaptive phase.

PMID- 29601996
TI  - Vancomycin and daptomycin minimum inhibitory concentrations as a predictor of
      outcome of methicillin-resistant Staphylococcus aureus bacteraemia.
AB  - OBJECTIVES: The aim of this study was to determine the persistence of the adverse
      prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC)
      in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting
      with low vancomycin use. METHODS: A retrospective study focusing on episodes of
      bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was
      designed. The main outcome measures were 30-day mortality and treatment failure.
      Multivariate logistic regression analysis was used to identify variables
      associated with patient mortality and treatment outcome. RESULTS: In total, 79
      MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0MUg/mL in 53
      episodes (67.1%). The presence of high vancomycin MIC was not associated with a
      higher mortality rate or treatment success. A daptomycin MIC>=0.5MUg/mL was
      present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained
      and was associated with 30-day mortality in the multivariate analysis (odds
      ratio=4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used
      were associated with a lower risk of treatment failure or mortality. CONCLUSIONS:
      The pernicious effect of high vancomycin MIC disappears in the absence of a
      predominant use of this antibiotic. However, a high daptomycin MIC in MRSA
      bacteraemia is associated with higher mortality in patients with bacteraemia,
      irrespective of antimicrobial treatment choice.

PMID- 29601997
TI  - Effectiveness of a carbohydrate restricted diet to treat non-alcoholic fatty
      liver disease in adolescents with obesity: Trial design and methodology.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver
      disorder among children in the developed world and can progress to cirrhosis,
      hepatocellular carcinoma, and liver failure. No evidence-based dietary guidelines
      exist on the most effective diet prescription to treat NAFLD. OBJECTIVE: To
      compare the effect of a carbohydrate (CHO)-restricted diet vs fat-restricted
      diet, the current standard of care, on changes in hepatic fat infiltration, body
      composition, and metabolic health over an 8-week period among overweight and
      obese children diagnosed with NAFLD. METHODS: In this two-arm, parallel design
      randomized controlled trial (RCT), 40 participants aged 9 to 18 years were
      randomized to a CHO restricted diet (<25:>50:25% daily calories from CHO: fat:
      protein) or control, fat restricted diet (55,20:25% daily calories from CHO: fat:
      protein). This family-based diet intervention included: (1) a 2-week supply of
      groceries to feed a four-person household specific to the assigned diet; and (2)
      extensive education on diet implementation through biweekly, diet-specific group
      and individualized counseling sessions with participants and one parent or
      guardian led by a registered dietitian (RD). The primary outcome measure of this
      study was hepatic lipid, measured using magnetic resonance spectroscopy (MRS).
      Secondary outcomes included liver transaminases; markers of inflammation (hsCRP,
      IL-6, TNF-alpha); body composition; visceral adipose tissue; and insulin
      resistance. All testing was conducted at baseline and week 8; hepatic
      transaminases were also measured at weeks 2 and 4. This RCT is registered with
      ClinicalTrials.gov (ID: NCT02787668).

PMID- 29601999
TI  - Author's Reply.

PMID- 29601998
TI  - Biomarkers of GH action in children and adults.
AB  - Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the
      diagnosis and management of GH-related disorders but have not been subject to
      structured validation. Auxological parameters in children and changes in body
      composition in adults, as well as metabolic parameters and patient related
      outcomes are used as clinical and surrogate endpoints. New treatment options,
      such as long acting GH and GH antagonists, require reevaluation of the currently
      used biochemical biomarkers. This article will review biomarkers, surrogate
      endpoints and clinical endpoints related to GH treatment in children and adults
      as well as in acromegaly.

PMID- 29602000
TI  - Author's Reply.

PMID- 29602001
TI  - Introduction of a Novel Modification in Laparoscopic Hysterectomy: The Bakay
      Technique.
AB  - The last step of laparoscopic hysterectomy when the surgeon attempts to remove
      the uterus and close the vaginal cuff (colpotomy and cuff closure) is considered
      the most challenging part of the operation, and the procedure involves a steep
      learning curve for surgeons. Although various methods have been described and
      reviewed on vaginal cuff closure in laparoscopic hysterectomy, this study is the
      first to describe placing a single continuous running purse-string suture using
      the uterine manipulator to maintain a safe distance between adjacent structures
      while facilitating the closure before colpotomy.

PMID- 29602002
TI  - Hysteroscopic Intact Removal of an Angular Pregnancy with a 5Fr Electrode.
AB  - STUDY OBJECTIVE: Angular pregnancy is a rare and life-threatening condition in
      which the embryo is implanted in the lateral angle of the uterine cavity, medial
      to the uterotubal junction and round ligament. Angular pregnancy is associated
      with a high risk of uterine rupture of about 23% [1]. No consensus has been
      achieved regarding the diagnostic and therapeutic approach of angular pregnancy
      [2]. Thus, the aim of this study was to report a case of hysteroscopic treatment
      of an angular pregnancy in a 34-year-old women. DESIGN: Step-by-step video
      presentation of the surgical treatment (Canadian Task Force classification III).
      SETTING: Department of Neuroscience, Reproductive Sciences and Dentistry, School
      of Medicine, University of Naples Federico II, Naples, Italy. PATIENT: A 34-year
      old woman. Written informed consent was obtained from the patient. INTERVENTION:
      Hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A 34-year-old woman was admitted to
      our Department with pelvic pain at 6 weeks of gestation. beta-Human chorionic
      gonadotropin (beta-hCG) was 5331 mIU/mL. The transvaginal ultrasound showed a
      gestational sac of 15 * 11 mm in the left uterine angle of an embryo without
      cardiac activity. The woman opted for a conservative approach with multiple-dose
      methotrexate [3]. Five days later the beta-hCG increased to 7589 mIU/mL with no
      regression of pregnancy at the transvaginal ultrasound. Therefore, a surgical
      approach was offered to the patient [4,5]. Laparoscopy showed normal salpinges,
      whereas hysteroscopy identified the gestational sac in the left uterine angle. A
      5Fr bipolar electrode was used to open the gestational capsular decidua. The
      chorionic villi were progressively separated from the implantation site. Using
      grasping forceps we removed the specimen for histologic examination. Histologic
      examination confirmed the diagnosis of angular pregnancy. On the second
      postoperative day beta-hCG was 1131 mIU/mL, and the patient was discharged the
      day after. At the 1-month follow-up visit, beta-hCG and transvaginal ultrasound
      were negative for pregnancy. The office hysteroscopy showed an empty uterine
      cavity at 3-months' follow-up. CONCLUSION: Our case shows that hysteroscopy may
      be used as a diagnostic and therapeutic tool for angular pregnancy, providing a
      unique image of the intact removal of the gestational sac.

PMID- 29602003
TI  - Deep Brain Stimulation Surgery for Status Dystonicus: A Single-Center Experience
      and Literature Review.
AB  - BACKGROUND: Status dystonicus (SD) is a life-threatening complication in which
      episodes of dystonic movements become increasingly frequent and severe, requiring
      urgent hospital admission, and can lead to respiratory, metabolic, and bulbar
      complications. Pharmacologic treatment has been the mainstay management for this
      complication; however, many refractory patients will still require further
      treatment. Deep brain stimulation (DBS) is an established therapeutic strategy
      that has been used for dystonia, and now it has been proposed to be used for SD.
      METHODS: In this case series, we describe our experience with early DBS placement
      in 5 patients with SD to control symptoms that are refractory to pharmacologic
      therapy. In addition, we present a literature review of this therapy in the
      treatment of SD. RESULTS: Before discharge, symptomatic relief (decrease of
      dystonic movements and resolution of abnormal postures) was evidenced in all
      patients with a median of 3 days (interquartile range, 1-7) after surgery was
      performed. A follow-up Unified Dystonia Rating Scale score and Burke-Fahn-Marsden
      rating scale motor subscale score, at 6 months after hospital discharge with
      values being inferior to 20 and 30, respectively, for all cases. None of the
      patients had a recurrence of SD in the last follow-up period. CONCLUSIONS: DBS
      surgery is a suitable, versatile, reversible and adequate therapy in the
      treatment of SD that is refractory to initial pharmacologic treatment.

PMID- 29602004
TI  - Shape of the Spinal Canal Is Not Associated with Success Rates of Microsurgical
      Unilateral Laminotomy and Bilateral Decompression for Lumbar Spinal Canal
      Stenosis.
AB  - BACKGROUND: Anatomic shape of the spinal canal (oval, round, trefoil) has been
      reported to predict outcome of bilateral decompression performed in an
      undercutting technique via unilateral laminotomy in monosegmental lumbar spinal
      stenosis, with poorest results observed in a trefoil spinal canal, leading to the
      proposal of using bilateral instead of unilateral laminotomy. The aim of this
      study was to assess whether this anatomic classification into oval, round, and
      trefoil shapes is relevant to surgical treatment of lumbar spinal stenosis.
      METHODS: Retrospective chart review of patients undergoing lumbar decompression
      surgery was performed. Spinal canal configuration was assessed on preoperative
      computed tomography based on maximal transverse and anteroposterior diameter, and
      shapes were classified into oval, round, and trefoil. Associations between spinal
      canal shape and outcome improvement (aggregate of walking distance and leg pain)
      were tested. RESULTS: Decompression of 236 lumbar levels was performed in 159
      patients (mean age, 73 +/- 8 years; mean body mass index, 29 +/- 6). Average
      number of operated segments was 1.3 +/- 0.6. Oval configurations were detected in
      155 (65%) levels, round configurations were detected in 11 (5%) levels, and
      trefoil configurations were detected in 70 (30%) levels. Postoperative
      improvement was recorded in 91.7% of patients. Spinal canal shape had no
      influence on surgical outcome (oval, area under the curve 0.529, P = 0.672;
      trefoil, area under the curve 0.500, P = 0.997; round, area under the curve
      0.471, P = 0.670). CONCLUSIONS: Spinal canal configuration varies in frequency
      with lumbar segment. Our results do not support the idea that this anatomic
      classification, particularly the nomenclature of oval, round, and trefoil, should
      influence surgical decision making.

PMID- 29602005
TI  - Transventricular Transvelar Approach to Trochlear Nerve Schwannoma: Novel
      Technique to Lesions of Inferior Pineal Region.
AB  - OBJECTIVES: The schwannoma of the trochlear nerve is rare and originates mostly
      from the distal parts in the interpeduncular cistern. A lesion on the proximal
      segment in the inferior pineal region is extremely rare. Because of the rarity of
      the disease, the surgical approach to this region for the resection of trochlear
      nerve schwannoma has not been well documented in the literature. We herein
      describe a novel approach to successfully resect the trochlear nerve schwannoma.
      METHODS: A 12-year-old boy presented with occipital headache, abnormal gait, and
      disturbed conjoined eye movement. He was diagnosed with a lesion in the inferior
      pineal region compressing the superior medullary velum into the roof of the
      fourth ventricle. A bilateral midline suboccipital craniotomy was performed, and
      the fourth ventricle was exposed. The lesion was approached through the fourth
      ventricle superior medullary velum (transventricular transvelar approach). The
      lesion was totally resected, and his histopathology examination revealed
      trochlear schwannoma. RESULTS: The patient's symptoms resolved, and he had no
      recurrence at 12-year follow-up with normal eye movement and vision. CONCLUSION:
      The transventricular transvelar approach is feasible and safe to treat a lesion
      of the lower part of the pineal region being pushed through the superior
      medullary velum.

PMID- 29602006
TI  - Microsurgical Clipping of Basilar Apex Aneurysms: A Systematic Historical Review
      of Approaches and their Results.
AB  - OBJECTIVE: Neck clipping remains a valuable treatment option for basilar apex
      aneurysms, especially in those with complex morphology, such as incorporation of
      branching vessels or large size, and young patient age. Several approaches have
      proved to give effective exposure for various types of lesion morphologies. Our
      historic literature review from 1976 to the present systematically compares the
      outcomes and complications of the key surgical approaches in the treatment of
      basilar apex aneurysms. METHODS: We searched PubMed for articles with at least 5
      patients, data on neurologic outcome, and procedure-associated complications for
      the following approaches: pterional or orbitozygomatic transsylvian, subtemporal
      (with or without zygomatic osteotomy), pretemporal (with or without
      transcavernous extension), and transpetrous. n-Weighted averages for clinical
      outcome, aneurysm occlusion rates, morbidity, mortality, and aneurysm morphology
      were compared. RESULTS: Of 35 articles selected, 2041 patients with 722 ruptured
      aneurysms underwent microsurgery, including 1131 transsylvian, 241 pretemporal,
      375 subtemporal, and 17 transpetrous approaches. Comparing these 4 approaches in
      n-weighted averages, respectively, we noted good neurologic outcomes (81%, 85%,
      81%, and 58%), surgical morbidity (14%, 10%, 34%, and 53%), surgical mortality
      (4%, 1%, 0, and 1%), and complete occlusion rates (95%, 94%, 86%, and 75%).
      CONCLUSIONS: Transsylvian, pretemporal, and subtemporal approaches showed
      favorable neurologic outcomes at similar rates and were applied for aneurysms
      located between -1mm and +7mm in relation to the posterior clinoid process. The
      pretemporal approach was preferably applied to large and giant aneurysms with
      good outcome; the transsylvian approach was most frequently used for ruptured
      aneurysms.

PMID- 29602007
TI  - Successful Kissing Balloon Expandable Stent Graft Treatment for a Right Common
      Carotid Pseudoaneurysm Caused by Tracheotomy.
AB  - BACKGROUND: A rare complication following tracheotomy is common carotid artery
      (CCA) pseudoaneurysm. Treatment modalities for CCA pseudoaneurysm include
      surgical repair and single-artery balloon-covered stent graft technique. We
      describe successful treatment of tracheotomy-related CCA pseudoaneurysm with the
      "kissing balloon" expandable stent graft technique. CASE DESCRIPTION: We
      successfully implemented the kissing balloon expandable stent graft technique for
      treatment of a large, narrow-necked, bilobed CCA pseudoaneurysm that arose owing
      to a tracheotomy complication. The pseudoaneurysm was detected while performing a
      diagnostic angiogram of the aortic arch and surrounding vessels. The stent was
      deployed while the 2 balloons were introduced in a kissing manner such that they
      faced one another to avoid occlusion of either branch of the innominate artery
      coming into contact; 1 balloon was inflated at the origin of the right subclavian
      artery, and the other was inflated at the right innominate artery simultaneously.
      The pseudoaneurysm was successfully contained; normal blood flow was restored in
      the CCA. The balloons were deflated and withdrawn. The patient remained
      neurologically intact after the procedure. CONCLUSIONS: The kissing balloon
      technique is a safe and effective alternative to surgical repair, as it prevents
      morbidities associated with the surgical procedure. Also, this technique
      decreases the risk of major side-branch occlusion associated with the single
      artery balloon-covered stent graft technique.

PMID- 29602008
TI  - Complications of Full-Endoscopic Versus Microendoscopic Foraminotomy for Cervical
      Radiculopathy: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Minimally invasive surgery of posterior cervical foraminotomy (PCF)
      for symptomatic radiculopathy has gained popularity in the last decade. It
      remains to be determined whether the 2 dominant operation techniques, full
      endoscopic (FE) or microendoscopic (MI), are associated with fewer complications.
      METHODS: An electronic retrieval from PubMed, Embase, and Web of Science was
      performed to identify comparative or single-arm studies concerning FE-PCF and MI
      PCF. The pooled incidence of complications was calculated. RESULTS: A total of 26
      studies with 2028 patients (FE, 402; MI, 1626) were identified. The overall
      complication rate was 5.8% for FE-PCF and 3.5% for MI-PCF, with no significant
      difference (P = 0.115). The pooled complication rate for single-level
      radiculopathy showed no statistical difference (FE, 4.5%; MI, 3.5%; P = 0.471),
      either. However, constituent of complications showed apparent disparity, with
      transient root palsy in FE-PCF (15/19, 78.9%) and dural tear (20/47, 42.6%) in MI
      PCF being the most commonly reported. As for the subgroup analysis, both
      incidence of dural tear (FE, 1.5%; MI, 1.8%; P = 0.672) and superficial wound
      infection (FE, 2.2%; MI, 1.0%; P = 0.109) showed no statistical difference.
      Nevertheless, transient root palsy occurred at a higher incidence in the FE group
      than in the MI group (FE, 4.5%; MI, 1.5%; P = 0.002). CONCLUSIONS: Both FE-PCF
      and MI-PCF can offer relatively safe treatment for cervical radiculopathy. There
      is no significant difference in overall complication rate between the 2
      techniques. Dural tear is the most commonly reported complication of MI-PCF,
      whereas transient root palsy deserves to be noticed for surgeons performing FE
      PCF.

PMID- 29602009
TI  - Endovascular Recanalization of Occluded Dural Sinus in Patient with Dural
      Arteriovenous Fistulas: Case Report and Literature Review.
AB  - BACKGROUND: Symptomatic sinus occlusion complicated with dural arteriovenous
      fistulas (dAVFs) can be treated successfully endovascularly. However, no studies
      have reported the use of endovascular transvenous approaches alone to recanalize
      the occluded sinuses for treatment of the involved dAVFs without stent
      deployment. In this study, we presented a 75-year-old man with occlusion of the
      transverse and sigmoid sinuses complicated with a dAVF. CASE DESCRIPTION: This
      patient initially suffered intermittent headache, nausea, and vomiting but
      developed seizures and hemiplegic paralysis 2 months later. Neurologic
      examination revealed mildly decreased motor function in grade IV in the left
      limb. Intracranial pressure by lumbar puncture was 300 mm H2O. Magnetic resonance
      imaging venography disclosed sinus occlusion and dAVFs accounting for
      encephaledema. Cerebral angiography revealed occlusion of the left transverse and
      sigmoid sinuses and cortical reflux with the sinus junction unobstructed. The
      feeding arteries of the left transverse sinus dAVFs were muscular branches of the
      left vertebral artery and external carotid artery, and the draining vein was from
      the superior sagittal sinus to the contralateral transverse sinus. Balloon
      angioplasty plus mechanical cracking (pulling a microcatheter back and forth) was
      used to recanalize the occluded sinuses. The symptoms disappeared after
      endovascular recanalization of the occluded left transverse sinus and sigmoid
      sinuses, and follow-up venography revealed opened sinuses with complete
      disappearance of the dAVF. CONCLUSION: Endovascular transvenous recanalization
      may be a better alternative therapy for selected patients with dural
      arteriovenous fistulas complicated by sinus occlusion without stent deployment.

PMID- 29602010
TI  - Zirconia-Polyurethane Aneurysm Clip.
AB  - OBJECTIVE: Susceptibility artifacts from metal clips in magnetic resonance (MR)
      imaging present an obstacle to evaluating the status of clipped aneurysms, parent
      arteries, and adjacent brain parenchyma. We aimed to develop MR-compatible
      aneurysm clips. METHODS: Considering the mechanical and biologic properties, as
      well as MR compatibility of candidate materials, a prototype clip with a zirconia
      body and a polyurethane head spring (zirconia clip [ZC], straight, 9-mm long) was
      developed. The closing forces, opening width of blades, and in vitro and in vivo
      artifact volumes in 3 tesla MR imaging were compared among the prototype and
      commercial metal clips such as a Yasargil clip (YC, curved type, 8.3-mm long) and
      a Sugita clip (SC, straight type, 10-mm long). An in vivo animal study was
      performed with a canine venous pouch aneurysm model. RESULTS: The closing forces
      (N) at 1 mm and 8 mm from the blade tip were 2.09 and 3.77 in YC, 1.85 and 3.04
      in SC, and 2.05 and 4.60 in ZC. The maximum opening widths (mm) was 6.8, 9.0, and
      3.0 in YC, SC, and ZC, respectively. The in vitro artifact volumes of YC, SC, and
      ZC in time-of-flight MR imaging were 26.9, 29.7, and 1.9 times larger than the
      respective real volumes. The in vivo artifact volumes of YC, SC, and ZC were
      respectively 21.4, 29.4, and 2.6 times larger than real ones. CONCLUSIONS: ZC
      showed the smallest susceptibility artifacts and satisfactory closing forces.
      However, the narrow opening width of the blades was a weak point.

PMID- 29602011
TI  - TransArterial ChemoEmbolization (TACE) with platinum versus anthracyclines for
      hepatocellular carcinoma: A meta-analysis.
AB  - OBJECTIVE: To determine the clinical efficacy of TACE with platinum versus
      anthracyclines for hepatocellular carcinoma (HCC) patients using a meta-analysis.
      METHODS: We conducted a systematic review of the literature in PubMed, Embase,
      and the Cochrane Library database to discover relevant randomized controlled
      trials (RCTs) and observational studies. Data on therapeutic response, adverse
      event and overall survival rate from studies that compared TACE with platinum
      versus anthracyclines for HCC patients was extracted for pooled estimation.
      Subgroup analysis was used if further investigation was needed. The Q statistic
      and the I2 index statistic were used to assess heterogeneity. Publication bias
      was evaluated using Egger's test. RESULTS: Four RCTs and seven observational
      studies containing 1405 patients were included in this meta-analysis. After
      comparing RCTs and observational studies separately, the pooled estimation
      results indicated that no significant difference existed between platinum and
      anthracyclines regarding therapeutic response, adverse event and overall survival
      rate. Furthermore, Egger's test revealed bias in pooled estimation of survival
      rate among RCTs. CONCLUSIONS: Based on current results, we concluded that TACE
      with platinum revealed similar clinical efficacy compared with anthracyclines.
      And more relative studies in this field were expected in the future.

PMID- 29602012
TI  - Distal versus total gastrectomy for middle and lower-third gastric cancer: A
      systematic review and meta-analysis.
AB  - BACKGROUND: The optimal resection extent for middle or lower-third gastric cancer
      still remains controversial. This study was aim to compare the safety and long
      term prognosis of distal gastrectomy (DG) with total gastrectomy (TG) for middle
      and lower-third gastric cancer. METHODS: Pubmed, EMBASE, the Cochrane Library,
      and Web of Science were searched from inception to October 2017 for comparative
      studies comparing DG with TG for middle or lower-third gastric cancer. We
      performed the meta-analysis using RevMan 5.3 software. RESULTS: Overall, 11
      comparative studies with 3554 patients, including 4 randomized controlled trials
      and 7 retrospective cohort studies, were analyzed. Compared with DG, TG showed a
      higher rate of overall postoperative complication, anastomosis leakage, wound
      complication, peritoneal abscess, and mortality. There were no significant
      differences between the two groups in rate of recurrence and cancer-related
      death. The 5-year overall survival is better in the DG group than in the TG
      group, but no significant differences were found in stage-specific analysis.
      CONCLUSIONS: Compared with TG, DG is an optimal surgical procedure for middle or
      lower-third gastric cancer in early and locally advanced stages with better short
      term outcomes and comparable long-term prognosis under the precondition of
      negative proximal resection margin.

PMID- 29602013
TI  - DNA methylation as an epigenetic regulator of gallbladder cancer: An overview.
AB  - Gallbladder cancer (GBC) is a lethal health issue affecting mostly the women in
      their middle-age. High incidence of GBC has been reported across the world
      specifically in Asian countries, India and Pakistan. The exact etiology remains
      unknown, although several risk factors and genetic aberrations involving
      mutations or epigenetic changes may be involved in gallbladder carcinogenesis.
      This article presents a review of the published literature mainly from the year
      2003 onwards. The topic of main concerns was epigenetic regulation of GBC. All
      relevant studies identified were included and are described according to the
      aforementioned subheadings. In this review, we have discussed the role of DNA
      methylation in GBC, clinical implication and future prospects of biomarker
      development for early diagnosis and therapeutic interventions.

PMID- 29602014
TI  - The clinicopathological and prognostic value of Nanog in human gastrointestinal
      luminal cancer: A meta-analysis.
AB  - BACKGROUND: Recent studies have demonstrated that the over-expression of Nanog
      contributes to the progression of various malignant tumors. However, the
      clinicopathological and prognostic role of Nanog in gastrointestinal luminal
      cancer remains controversial. Therefore, we conducted a meta-analysis to assess
      the role of Nanog in gastrointestinal luminal cancer. METHODS: An electronic
      search for relevant literature was performed in PubMed, Cochrane Library, Web of
      Science, and EMBASE databases. The relationships between Nanog expression and
      clinicopathological features and survival outcomes were analyzed. Pooled odds
      ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were
      calculated by STATA14.2 and RevMan 5.3 software. RESULTS: A total of 9 studies
      with 1526 patients were included in this meta-analysis. The positive expression
      of Nanog was related to gender, depth of infiltration, differentiation, and TNM
      stage; however, it was not associated with age, tumor size, or lymph node
      metastasis. Moreover, positive Nanog expression was correlated with a poor
      overall survival (OS) and poor disease-free survival (DFS) in gastrointestinal
      luminal cancer. CONCLUSION: The pooled results suggested that Nanog expression
      was associated with gender, depth of infiltration, differentiation, and TNM
      stage, and Nanog may be a potential biomarker to predict the prognosis of
      gastrointestinal luminal cancer.

PMID- 29602015
TI  - Geriatric Nutritional Risk Index as a prognostic factor in patients with
      esophageal squamous cell carcinoma -retrospective cohort study.
AB  - PURPOSE: The Geriatric Nutritional Risk Index (GNRI) is a new index recently
      introduced to predict the risk of nutrition-related complications and mortality.
      Our aim is to examine the association between the GNRI and long-term prognosis in
      patients with esophageal squamous cell carcinoma (ESCC) who underwent
      esophagectomy. METHODS: The present study enrolled consecutive 216 patients with
      ESCC who underwent esophagectomy. The GNRI at admission to the hospital was
      calculated as follows: (1.489 * albumin, g/l) + (41.7 * present/ideal body
      weight). The characteristics and long-term prognosis were compared between four
      groups: the severe risk (GNRI: <82), moderate risk (GNRI: 82 to <92), low risk
      (GNRI: 92 to <98) and no risk (GNRI: >98) groups. The 5-year overall survival and
      independent prognostic factors were investigated, respectively. RESULTS: A
      decreased GNRI significantly correlated with unfavorable overall survival (p <
      0.001). In all patients, a multivariate analysis demonstrated that the severe and
      moderate risk groups (GNRI: <92) (hazard ratio 0.50; p = 0.002), T factor (>=T2)
      (hazard ratio 0.52; p = 0.026), and N positive factor (hazard ratio 0.47; p =
      0.004) were independent prognostic factors. In the subgroup analysis, which
      excluded patients with preoperative chemoradiotherapy, the severe and moderate
      risk groups (GNRI: <92) (hazard ratio 0.48; p = 0.0057), and T factor (>=T2)
      (hazard ratio; p = 0.021) were independent prognostic factors. CONCLUSIONS: GNRI
      is considered to be a useful prognostic factor in patients with ESCC undergoing
      esophagectomy.

PMID- 29602016
TI  - Role of liver resection in treating intermediate and advanced stage adolescent
      and young adult hepatocellular carcinoma patients: A propensity-matching cohort
      study.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) in adolescent and younger adult (AYA)
      patients is usually diagnosed at an advanced stage such that curative treatments
      are often not possible. The aimed of this study was to compare the outcome of
      attempted curative treatment, liver resection (LR) versus transarterial
      chemoembolization (TACE), in AYA patients presenting with intermediate or
      advanced HCC defined by the Barcelona Clinic Liver Cancer (BCLC) stage B and C.
      METHODS: All AYA patients diagnosed with BCLC stage B or C HCC undertaking LR (n
      = 276) and TACE (n = 136) were included in our study. The prognostic factors of
      the patients were analyzed and the propensity score-matched patients (120 pairs)
      were analyzed to adjust for any baseline differences. RESULTS: The overall
      survival rate of the patients undertaking LR was higher than TACE for the both
      entire and the propensity matched population (p < 0.001). In the multivariate
      analysis, propensity scoring analyses suggested that HBsAg positivity,
      macrovascular invasion, tumor size and TACE treatment were the independent
      prognostic factors associated with a worse survival outcome. CONCLUSION: The
      effect of LR was superior to that of TACE for patients with intermediate and
      advanced stage HCC. The survival outcome was associated with the tumor size,
      macrovascular invasion, and hepatitis history in AYA HCC patients.

PMID- 29602017
TI  - Assessing safety and feasibility of 'pure' laparoscopic total gastrectomy for
      advanced gastric cancer in the West. Review article.
AB  - BACKGROUND: Gastric cancer is reported to be the fourth most common cancer and
      the second leading cause of cancer-related death worldwide. Minimally invasive
      surgical treatment for gastric cancer is a very challenging approach which offers
      undoubtedly important advantages. MATERIALS AND METHODS: There is intense debate
      concerning the minimally invasive surgical approach for advanced gastric cancer
      especially in the Western population. A careful literature search was conducted
      in order to clarify the feasibility and safety of pure laparoscopic total
      gastrectomy in the West. RESULTS: Herewith we aim to summarize the current
      scientific evidence assessing the feasibility and short-term outcomes of
      laparoscopic gastrectomy for advanced gastric cancer in the West. A lack of data
      from Western institutions regarding minimally invasive surgical approach for
      gastric cancer is yet a reality. Nevertheless, the laparoscopic procedure appears
      to provide satisfactory short-term oncologic outcomes and improved postoperative
      outcomes. CONCLUSION: It is obvious that future well-conducted trials on long
      term results are necessary for Western patients in order safe conclusions to be
      reached regarding a potential definitive 'place' for laparoscopy in the curative
      gastric cancer treatment.

PMID- 29602018
TI  - Low dose caffeine as a salivary tracer for the determination of gastric water
      emptying in fed and fasted state: A MRI validation study.
AB  - Improving our knowledge about human gastrointestinal physiology and its impact on
      oral drug delivery is crucial for the development of new therapies and effective
      drug delivery systems. The aim of this study was to develop an in vivo tool to
      determine gastric emptying of water by administration of a caffeine as a tracer
      substance followed by subsequent saliva caffeine analysis. For this purpose, 35
      mg of caffeine were given to six healthy volunteers after a 10 h overnight
      together with 240 mL of tap water either on a fasted stomach or 30 min after the
      high-caloric, high-fat breakfast recommended for bioavailability/bioequivalence
      (BA/BE) studies. Caffeine was administered in form of an ice capsule in order to
      omit the contamination of the oral cavity with caffeine. Parallel to saliva
      sampling, magnetic resonance imaging (MRI) was applied in order to validate this
      novel approach. After administration of the ice capsule, MRI measurements were
      performed every 2 min for the first 20 min followed by further measurements after
      25, 30, 35, 40, 50 and 60 min. Saliva samples were collected always 1 min after
      the MRI measurement in supine position in the MRI scanner and continued for
      further 240 min. The caffeine concentration in saliva was quantified after liquid
      liquid extraction by a validated HPLC/MS-MS method. The obtained MRI data
      revealed a fast emptying of the co-administered water within 10 to 50 min in the
      fasted state and likewise in the fed state. Salivary caffeine kinetics showed a
      Cmax from 150 to 400 ng/mL with a tmax from 20 to 90 min. MRI data were
      normalized by setting the maximum emptied volume to 100% and the salivary
      caffeine kinetics were normalized by setting Cmax to 100%. In order to compare
      the results obtained by the MRI and the saliva method, the normalized data for
      each volunteer was correlated based on a linear regression. In the fasted state
      the mean slope for six comparisons was 0.9114 +/- 0.1500 and the mean correlation
      coefficient was 0.912 +/- 0.055. In the fed state, a mean slope of 0.8326 +/-
      0.1630 and a mean correlation coefficient of 0.887 +/- 0.047 were obtained. Based
      on these results, we could show that salivary caffeine concentrations are
      suitable to describe the emptying of water as a non-caloric liquid from the
      fasted and the fed stomach. The presented technique provides a straight-forward,
      inexpensive and noninvasive method to assess gastric emptying of hydrophilic
      liquids, which can be broadly used in oral biopharmaceutics. Possible
      applications are the characterization of real-life conditions, specific
      populations (e.g. elderly people) and the better understanding of the
      contribution of gastric emptying to pharmacokinetic profiles of orally
      administered drugs.

PMID- 29602019
TI  - Investigation and simulation of dissolution with concurrent degradation under
      healthy and hypoalbuminaemic simulated parenteral conditions- case example
      Amphotericin B.
AB  - Guidance on dissolution testing for parenteral formulations is limited and not
      often related in vivo performance. Critically ill patients represent a target
      cohort, frequently hypoalbuminaemic, to whom certain parenteral formulations are
      administered. Amphotericin B (AmB) is a poorly soluble, highly protein-bound
      drug, available as lipid-based formulations and used in critical illness. The aim
      of this study was to develop media representing hypoalbuminaemic and healthy
      plasma, and to understand and simulate the dissolution profile of AmB in
      biorelevant media. Dissolution media were prepared with bovine serum albumin
      (BSA) in Krebs-Ringer buffer, and tested in a flow through cell apparatus and a
      bottle/stirrer setup. Drug activity was tested against Candida albicans. BSA
      concentration was positively associated with solubility, degradation rate and
      maximum amount dissolved and negatively associated with dissolution rate constant
      and antifungal activity. In the bottle/stirrer setup, a biexponential model
      successfully described simultaneous dissolution and degradation and increased in
      agitation reduced the discriminatory ability of the test. The hydrodynamics
      provided by the flow-through cell apparatus was not adequate to dissolve the
      drug. Establishing discriminating test methods with albumin present in the
      dissolution media, representing the target population, supports future
      development of biorelevant and clinically relevant tests for parenteral
      formulations.

PMID- 29602020
TI  - Mimicking brain tissue binding in an in vitro model of the blood-brain barrier
      illustrates differences between in vitro and in vivo methods for assessing the
      rate of brain penetration.
AB  - Assessing the rate of drug delivery to the central nervous system (CNS) in vitro
      has been used for decades to predict whether CNS drug candidates are likely to
      attain their pharmacological targets, located within the brain parenchyma, at an
      effective dose. The predictive value of in vitro blood-brain barrier (BBB) models
      is therefore frequently assessed by comparing in vitro BBB permeability, usually
      quoted as the endothelial permeability coefficient (Pe) or apparent permeability
      (Papp), to their rate of BBB permeation measured in vivo, the latter being
      commonly assessed in rodents. In collaboration with AstraZeneca (DMPK department,
      Sodertalje, Sweden), the in vitro BBB permeability (Papp and Pe) of 27 marketed
      CNS drugs has been determined using a bovine in vitro BBB model and compared to
      their in vivo permeability (Pvivo), obtained by rat in-situ brain perfusion. The
      latter was taken from published data from Summerfield et al. (2007). This
      comparison confirmed previous reports, showing a strong in vitro/in vivo
      correlation for hydrophilic compounds, characterized by low brain tissue binding
      and a weak correlation for lipophilic compounds, characterized by high brain
      tissue binding. This observation can be explained by the influence of brain
      tissue binding on the uptake of drugs into the CNS in vivo and the absence of
      possible brain tissue binding in vitro. The use of glial cells (GC) in the in
      vitro BBB model to mimic brain tissue binding and the introduction of a new
      calculation method for in vitro BBB permeability (Pvitro) resulted in a strong
      correlation between the in vitro and in vivo rate of BBB permeation for the whole
      set of compounds. These findings might facilitate further in vitro to in vivo
      extrapolation for CNS drug candidates.

PMID- 29602021
TI  - A comparison of two biorelevant in vitro drug release methods for
      nanotherapeutics based on advanced physiologically-based pharmacokinetic
      modelling.
AB  - As a growing number of nanotherapeutics enters the market, improved analytical
      techniques for measuring the drug release are required. Biorelevant release tests
      have become a standard in the prediction of in vivo pharmacokinetics but also in
      quality control of novel dosage forms. In the present study, two methods for
      testing the drug release from nanocarriers, namely the filtration technique and
      the dispersion releaser technology, have been investigated. Initially, the in
      vitro release rates were determined using two different biorelevant media.
      Additionally, the effect of each method on a simulated in vivo pharmacokinetic
      profile was studied using advanced PBPK modelling. The two methods resulted in
      slightly different release profiles. Applying the filtration method, an early
      plateau of 91.0 +/- 5.3% was reached at the first sampling time point. In
      comparison, the release rate steadily increased to a maximum of 100.9 +/- 4.1%
      when the dispersion releaser technology was used. Sensitivity analysis revealed
      how these differences translated into the PBPK-based simulation. A change in the
      total dissolution rate of 10% resulted in cmax values of +1.6% and -11.0%,
      respectively, when using input data obtained with the dispersion releaser. Data
      obtained by filtration translated into cmax values of +/-1.8%.

PMID- 29602022
TI  - Modeling Alzheimer's disease cognitive scores using multi-task sparse group
      lasso.
AB  - Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by
      loss of memory and reduction in cognitive functions due to progressive
      degeneration of neurons and their connections, eventually leading to death. In
      this paper, we consider the problem of simultaneously predicting several
      different cognitive scores associated with categorizing subjects as normal, mild
      cognitive impairment (MCI), or Alzheimer's disease (AD) in a multi-task learning
      framework using features extracted from brain images obtained from ADNI
      (Alzheimer's Disease Neuroimaging Initiative). To solve the problem, we present a
      multi-task sparse group lasso (MT-SGL) framework, which estimates sparse features
      coupled across tasks, and can work with loss functions associated with any
      Generalized Linear Models. Through comparisons with a variety of baseline models
      using multiple evaluation metrics, we illustrate the promising predictive
      performance of MT-SGL on ADNI along with its ability to identify brain regions
      more likely to help the characterization Alzheimer's disease progression.

PMID- 29602023
TI  - "What the mind does not know, the eyes do not see". Placing food allergy risk in
      sub-Saharan Africa.
AB  - Policy makers and health geographers are increasingly intrigued by the global
      rise of chronic disease. While current engagement coalesce around cardiovascular
      disease, cancers, chronic respiratory disease, and diabetes, very little
      attention has been given to other important chronic conditions: e.g., allergic
      disease. Concerns about how health is shaped by context and experienced in place
      can provide important insights to understand the trajectory of allergic disease
      and inform policy especially in developing countries experiencing an
      epidemiologic transition. Using Ghana as a case study. this paper draw on
      theories of political ecology of health to enhance our understanding of how
      individual (e.g. care seeking behaviours), sociocultural (e.g. lack of education
      and awareness), health system (e.g. absence of logistics) and policy environments
      (e.g. absence of policy) influence the ways in which food allergy is perceived,
      diagnosed and managed. These findings highlight the need for decision makers to
      target structural factors that impede access to and utilization of healthcare,
      diagnostic practices, as well as food allergy coping and management strategies.
      Moreover, the findings highlight the need for a global health agenda that pays
      critical attention to place-based factors in the construction of emerging health
      risks.

PMID- 29602024
TI  - Colorimetric chemosensors based on diketopyrrolopyrrole for selective and
      reversible recognition of fluoride ions.
AB  - A series of colorimetric and reversible receptors for fluoride anions based on
      diketopyrrolopyrrole (DPP) were designed and synthesized successfully. The
      position of nitro substituent on the phenylhydrazide affected the alteration of
      photophysical properties to varying degrees. While the photoluminescence
      intensity of receptor 1 was weaker than that of receptor 2 and receptor 3 on
      account of the formation of intramolecular hydrogen bond deriving from oxygen
      atom of nitro substituent and hydrogen atom of hydrazide. The receptor 2 was a
      preferable chemosensor for responding fluoride anions. The fluorescence was
      quenched in the presence of fluoride anion resulted from the photo-induced
      electron transfer (PET) effect from the amide. The formation of deprotonation
      species, which produced by hydrazide NH moiety and F- was answerable for the
      spectral changes. Especially, the spectral and color responses of receptors could
      be switched back and forth successively by adding F- and HSO4- anions in DMSO
      solution. These receptors could response fluoride anion sensitively, visually and
      selectively in a manner of reversible with a low determination.

PMID- 29602025
TI  - Adaptive handling of Rayleigh and Raman scatter of fluorescence data based on
      evaluation of the degree of spectral overlap.
AB  - At present the general scatter handling methods are unsatisfactory when scatter
      and fluorescence seriously overlap in excitation emission matrix. In this study,
      an adaptive method for scatter handling of fluorescence data is proposed.
      Firstly, the Raman scatter was corrected by subtracting the baseline of deionized
      water which was collected in each experiment to adapt to the intensity
      fluctuations. Then, the degrees of spectral overlap between Rayleigh scatter and
      fluorescence were classified into three categories based on the distance between
      the spectral peaks. The corresponding algorithms, including setting to zero,
      fitting on single or both sides, were implemented after the evaluation of the
      degree of overlap for individual emission spectra. The proposed method minimized
      the number of fitting and interpolation processes, which reduced complexity,
      saved time, avoided overfitting, and most importantly assured the authenticity of
      data. Furthermore, the effectiveness of this procedure on the subsequent PARAFAC
      analysis was assessed and compared to Delaunay interpolation by conducting
      experiments with four typical organic chemicals and real water samples. Using
      this method, we conducted long-term monitoring of tap water and river water near
      a dyeing and printing plant. This method can be used for improving adaptability
      and accuracy in the scatter handling of fluorescence data.

PMID- 29602026
TI  - Biomethanization of citrus waste: Effect of waste characteristics and of storage
      on treatability and evaluation of limonene degradation.
AB  - This study proposes the evaluation of the suitability of mesophilic anaerobic
      digestion as a simple technology for the treatment of the citrus waste produced
      by small-medium agro-industrial enterprises involved in the transformation of
      Citrus fruits. Two different stocks of citrus peel waste were used (i.e., fresh
      and stored citrus peel waste), to evaluate the influence of waste composition
      (variability in the type of processed Citrus fruits) and of storage (potentially
      necessary to operate the anaerobic digester continuously over the whole year due
      to the seasonality of the production) on anaerobic degradation treatability. A
      thorough characterization of the two waste types has been performed, showing that
      the fresh one has a higher solid and organic content, and that, in spite of the
      similar values of oil fraction amounts, the two stocks are significantly
      different in the composition of essential oils (43% of limonene and 34% of
      linalyl acetate in the fresh citrus waste and 20% of limonene and 74% of linalyl
      acetate in the stored citrus waste). Contrarily to what observed in previous
      studies, anaerobic digestion was successful and no reactor acidification
      occurred. No inhibition by limonene and linalyl acetate even at the maximum
      applied organic load value (i.e., 2.72 gCODwaste/gVSinoculum) was observed in the
      treatment of the stored waste, with limonene and linalyl acetate concentrations
      of 104 mg/l and 385 mg/l, respectively. On the contrary, some inhibition was
      detected with fresh citrus peel waste when the organic load increased from 2.21
      to 2.88 gCODwaste/gVSinoculum, ascribable to limonene at initial concentration
      higher than 150 mg/l. A good conversion into methane was observed with fresh peel
      waste, up to 0.33  [Formula: see text] at the highest organic load, very close to
      the maximum theoretical value of 0.35 [Formula: see text] , while a lower
      efficiency was achieved with stored peel waste, with a reduction down to 0.24 
      [Formula: see text] at the highest organic load.

PMID- 29602027
TI  - Purification of residual leach liquors from hydrometallurgical process of NiMH
      spent batteries through micellar enhanced ultra filtration.
AB  - Hydrometallurgical processes for the treatment and recovery of metals from waste
      electrical and electronic equipment produce wastewaters containing heavy metals.
      These residual solutions cannot be discharged into the sewer without an
      appropriate treatment. Specific wastewater treatments integrated with the
      hydrometallurgical processes ensure a sustainable recycling loops of the
      electrical wastes to maximize the metals recovery and minimize the amount of
      wastes and wastewaters produced. In this research activity the efficiency of
      ultrafiltration combined with surfactant micelles (micellar-enhanced
      ultrafiltration) was tested to remove metals form leach liquors obtained after
      leaching of NiMH spent batteries. In the micellar-enhanced ultrafiltration, a
      surfactant is added into the aqueous stream containing contaminants or solute
      above its critical micelle concentration. When the surfactant concentration
      exceeding this critical value, the surfactant monomers will assemble and
      aggregate to form micelles having diameter larger than the pore diameter of
      ultrafiltration membrane. Micelles containing contaminants whose diameter is
      larger than membrane pore size will be rejected during ultrafiltration process,
      leaving only water, unsolubilized contaminants and surfactant monomers in
      permeate stream. The experiments are carried out in a lab-scale plant, where a
      tubular ceramic ultrafiltration membrane is used with adding a surfactant to
      concentrate heavy metals in the retentate stream, producing a permeate of
      purified water that can be reused inside the process, thus minimizing the fresh
      water consumption.

PMID- 29602028
TI  - Monte Carlo simulations and experimental results on neutron production in the
      uranium spallation target QUINTA irradiated with 660 MeV protons.
AB  - The activation experiment was performed using the accelerated beam of Phasotron
      accelerator at the Joint Institute for Nuclear Research (JINR). The natural
      uranium spallation target QUINTA was irradiated with protons with energy 660 MeV.
      Monte Carlo simulations of neutron production were performed using the Geant4
      code. The number of leakage neutrons from the sections of the uranium target
      surrounded by the lead shielding and the number of leakage neutrons from lead
      were determined. The total number of fissions in the setup QUINTA was determined.
      Experimental values of reaction rates for the produced nuclei in the 127I sample
      were obtained and several values of reaction rates were compared with the results
      of simulations. Experimentally determined fluence of neutrons in energy interval
      10-175 MeV using the (n,xn) reactions in the 127I(NaI) sample was compared with
      the results of simulations. Possibility of transmutation of the long-lived
      radionuclide 129I in the QUINTA setup was estimated.

PMID- 29602029
TI  - Universal scaling of transverse wave attenuation in polycrystals.
AB  - A single mode approximation for the transverse attenuation coefficient in
      polycrystals is obtained from the far field approximation model (Rokhlin et al.,
      2015). The model is applicable in all frequency ranges to polycrystals with
      ellipsoidal grains of triclinic symmetry and is shown to be in favorable
      agreement with other second order models. In the frame of this model, the
      transverse wave attenuation coefficient depends on a single elastic scattering
      factor only (it solely encompasses dependence on the crystallite elastic moduli
      and the elastic covariance). Therefore in this approximation the attenuation
      coefficient can be scaled with this factor (normalized), obtaining the universal
      (master) curve. The admissibility of scaling is supported by the use of the
      second order model (the type of Stanke-Kino) for a large number of material
      systems with different grain anisotropies. Within the second order model, the
      behavior of the scaled transverse wave attenuation coefficient versus frequency
      is nearly independent of the material system and is a function of the grain
      geometrical characteristics only. The scaling of the transverse wave attenuation
      coefficient is tested on the measurements for Ti alloy samples performed in this
      work and a large set of experimental data obtained for different material systems
      available in the literature. The results confirm the scaled coefficient
      independence of the material and good agreement between the data and the
      universal attenuation curve.

PMID- 29602030
TI  - Children's referential communication skills: The role of cognitive abilities and
      adult models of speech.
AB  - Referential communication is effective when speakers describe a specific entity
      in a way that leads to accurate identification of that referent among
      competitors. Young children's initial referential expressions are often
      inadequate, and this state of miscommunication needs to be repaired in subsequent
      communicative attempts. Exposure to adults' effective descriptions of referents
      is beneficial for children to develop referentially clear initial descriptions.
      Here, we examined whether adult models of speech also provide benefits for
      children's communicative repair behavior. Furthermore, we assessed the relation
      between children's cognitive abilities and referential communication skills. We
      tested 59 children (aged 4 years to 5 years 9 months) on their ability to request
      specific stickers among similar distractors in a pretest-modeling-posttest
      design. In the modeling phase, 30 children heard more informative descriptions of
      stickers with relative clauses (e.g., "you selected the horse that the boy is
      riding") and 29 children heard less informative descriptions with demonstrative
      noun phrases (e.g., "you selected that horse"). In a second session, we measured
      children's short-term memory, executive functions (working memory and cognitive
      flexibility), and theory of mind. Children who heard more informative expressions
      showed a greater increase in uniquely identifying initial descriptions than
      children who heard less informative expressions. Hearing more informative
      expressions did not provide an additional benefit in repairing ambiguous
      messages, an ability we found to be related to cognitive flexibility and memory.
      Results indicate that informative language structures that uniquely identify
      referents provide limited benefits to children for effective communication where
      children's short-term memory and executive functions also matter.

PMID- 29602031
TI  - Highly sensitive microfluidic paper-based photoelectrochemical sensing platform
      based on reversible photo-oxidation products and morphology-preferable multi
      plate ZnO nanoflowers.
AB  - A microfluidic paper-based analytical device (MUPAD) was simply constructed for
      highly sensitive detection of L-glutamic acid and L-cysteine. The MUPAD featured
      with two functional zones on one strip of paper achieved by preferable multi
      plate ZnO nanoflowers (ZnO NFs) and molecularly imprinting polymer (MIP)
      membranes. The as-designed MUPAD was established based on the inherent relation
      between the photo-oxidation products and photoelectrochemical (PEC) performance
      with the highly sensitive detection of biomolecules. The ZnO NFs were utilized to
      produce photo-oxidation products by driving the reaction between
      ferrocenemethanol and photogenerated holes under ultraviolet light. The photo
      oxidation products easily flowed to MIP membranes along the hydrophilic channel
      via capillary action. MIP membranes as the receptors specifically recognized the
      analytes as well as decreased the electron loss by blocking the reduction
      reaction between electrons and photo-oxidation products. The PEC response was
      obtained in the processes of electrons transfer and exhibited the direct
      relationships corresponding to the concentrations of target analytes. The MUPAD
      showed the detection limits toward L-glutamic acid and L-cysteine as low as 9.6
      pM and 24 pM, respectively. Moreover, it is interesting to point out that ZnO NFs
      nanostructure shows superior PEC signal compared with those of ZnO nanospheres,
      nanosheets, and nanorod arrays. In current work, photo-oxidation products are
      utilized to achieve highly sensitive PEC detection for biomolecules under
      ultraviolet light as well as avoid the effects of multiple modifications in the
      same region on the reproducibility, which is beneficial for opening up rich
      possibility for designing more efficient analytical strategy.

PMID- 29602032
TI  - Identification and characterisation of Staphylococcus aureus on low cost screen
      printed carbon electrodes using impedance spectroscopy.
AB  - Staphylococcus aureus infections are a cause of significant morbidity and
      mortality, in addition to representing a considerable economic burden. The aim of
      this study was to explore a low cost screen printed electrode as a sensor for the
      detection of S. aureus using impedance spectroscopy. S. aureus was incubated in
      chambers containing the electrodes and the results analysed using a novel
      normalisation approach. These results show that it is possible to detect the
      presence of S. aureus in LB media after 30 min incubation of a 1% growth culture,
      in addition to being able to see immediate cell concentration dependant changes
      in 0.9% NaCl. These observations imply that a number of electrochemical
      mechanisms cause a change in the impedance as a result of the presence of S.
      aureus, including adsorption to the electrode surface and the metabolism of the
      bacteria during growth. The study suggests that this detection approach would be
      useful in a number of clinical scenarios where S. aureus leads to difficult to
      treat infections.

PMID- 29602033
TI  - Molybdenum disulfide field-effect transistor biosensor for ultrasensitive
      detection of DNA by employing morpholino as probe.
AB  - This work reports on a molybdenum disulfide (MoS2) based field-effect transistor
      (FET) biosensor for ultrasensitive label-free detection of DNA via
      phosphorodiamidate morpholino oligos (PMO)-DNA hybridization. After the chip was
      fabricated and the sensing channel was modified with positive charges, the
      negatively charged MoS2 nanosheet was drop-casted onto the channel, enabling MoS2
      to tightly bind to the sensing surface via electrostatic interactions. Meanwhile,
      DNA analogue, PMO, was immobilized on the MoS2 surface, and detection of PMO-DNA
      hybridization was conducted by the fabricated MoS2 FET biosensor. Due to the
      neutral character and high affinity of PMO, a limit of detection (LOD) down to 6
      fM was obtained, which is lower than that of the previously reported MoS2 FET DNA
      biosensor based on DNA-DNA hybridization. In addition, the MoS2 FET biosensor
      also showed high sequence specificity capable of distinguishing the complementary
      DNA from one-base mismatched DNA, three-base mismatched DNA and noncomplementary
      DNA. Moreover, the unique FET biosensor was able to detect DNA in complex sample
      like serum, making the method potential in disease diagnostics.

PMID- 29602034
TI  - Automatic smartphone-based microfluidic biosensor system at the point of care.
AB  - Point-of-care testing technique is increasingly important for healthcare
      management in human being's daily life. However, traditional biosensor systems
      for health care are relatively expensive, bulky and hard-to-handle, which largely
      limits their use in point of care testing. The problems mentioned above are
      successfully addressed with the popularization of smartphone and the development
      of microfluidic technology for their applications of biosensor, which integrates
      smartphones, microfluidic components and sensory elements together, paving the
      way for wide application of smartphone-based microfluidic biomedical sensory
      system. According to the varieties of analytes, the most common sensing
      modalities of biosensor systems are divided into imaging analysis to detect cells
      and bacteria, biochemical analysis to detect blood sugar and blood fat,
      immunoassay to detect protein specifically bound to antibody, as well as
      molecular diagnosis to detect DNA and other biomolecules. Based on the most
      common analytical methods, this review article covers five types of smartphone
      based microfluidic biosensor systems at the point-of-care detection, i.e.,
      smartphone-based imaging biosensor, smartphone-based biochemical sensor,
      smartphone-based immune biosensor, smartphone-based hybrid biosensor with more
      than one sensing modality, and smartphone-based molecular sensor. We lay emphasis
      on reviewing the structures, analytical methods and sensing modalities about the
      four kinds of biosensor systems with detailed discussions on their application
      potentials, aiming at giving the audience an overview of the recent developments
      of automatic smartphone-based microfluidic biosensor systems, as well as their
      future prospective.

PMID- 29602035
TI  - A flexible and highly sensitive nonenzymatic glucose sensor based on DVD-laser
      scribed graphene substrate.
AB  - Flexible and implantable glucose biosensors are emerging technologies for
      continuous monitoring of blood-glucose of diabetes. Developing a flexible
      conductive substrates with high active surface area is critical for advancing the
      technology. Here, we successfully fabricate a flexible and highly sensitive
      nonenzymatic glucose by using DVD-laser scribed graphene (LSG) as a flexible
      conductively substrate. Copper nanoparticles (Cu-NPs) are electrodeposited as the
      catalyst. The LSG/Cu-NPs sensor demonstrates excellent catalytic activity toward
      glucose oxidation and exhibits a linear glucose detection range from 1 MUM to
      4.54 mM with high sensitivity (1.518 mA mM-1 cm-2) and low limit of detection
      (0.35 MUM). Moreover, the LSG/Cu-NPs sensor shows excellent reproducibility and
      long-term stability. It is also highly selective toward glucose oxidation under
      the presence of various interfering species. Excellent flexing stability is also
      demonstrated by the LSG/Cu-NPs sensor, which is capable of maintaining 83.9% of
      its initial current after being bent against a 4-mm diameter rod for 180 times.
      The LSG/Cu-NPs sensor shows great potential for practical application as a
      nonenzymatic glucose biosensor. Meanwhile, the LSG conductive substrate provides
      a platform for the developing next-generation flexible and potentially
      implantable bioelectronics and biosensors.

PMID- 29602036
TI  - Discovery of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as novel,
      potent and selective c-Met kinase inhibitors: Synthesis, SAR study, and
      biological activity.
AB  - A series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed,
      synthesized and evaluated for their biological activity. Most of these compounds
      showed potent activities against c-Met kinase and cell growth inhibition. The
      most promising compound, 7d, has the IC50 values of 2.02 and 88 nM to inhibit c
      Met kinase activity and cell growth in the MKN45 cell line, respectively. In
      addition, 7d is highly selective to c-Met and exhibits over 2500-fold selective
      inhibition to 16 tyrosine kinases evaluated.

PMID- 29602037
TI  - Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6
      trisubstituted-2H-pyrazolo[4,3-c]pyridines.
AB  - An efficient synthetic route for the synthesis of 2H-pyrazolo[4,3-c]pyridines,
      primarily varying by the substituents at the 2-, 4- and 6-positions, is described
      here. A Sonogashira-type cross-coupling reaction was employed to yield 3-alkynyl
      1H-pyrazole-4-carbaldehydes, ethanones and propanones from the corresponding 1H
      pyrazol-3-yl trifluoromethanesulfonates. Subsequent treatment of the coupling
      products with dry ammonia afforded a versatile library of 2H-pyrazolo[4,3
      c]pyridines, which were then evaluated for their cytotoxicity against K562 and
      MCF-7 cancer cell lines. The most potent of these compounds displayed low
      micromolar GI50 values in both cell lines. Active compounds induced dose
      dependent cell-cycle arrest in mitosis, as shown by flow cytometric analysis of
      DNA content and phosphorylation of histone H3 at serine-10. Moreover, biochemical
      assays revealed increased activities of caspases-3/7 in treated cells, specific
      fragmentation of PARP-1, and phosphorylation of Bcl-2, collectively confirming
      apoptosis as the mechanism of cell death.

PMID- 29602038
TI  - A comprehensive review of chalcone derivatives as antileishmanial agents.
AB  - Leishmaniasis is a group of infectious neglected tropical diseases caused by more
      than 20 pathogenic species of Leishmania sp. Due to the limitations of the
      current treatments available, chalcone moiety has been drawn with a lot of
      attention due to the simple chemistry and synthesis, being reported with
      antileishmanial activity in particular against amastigote form. This review aims
      to provide an overview towards antileishmanial activity of chalcones derivatives
      against amastigote form for Leishmania major, L. amazonensis, L. panamensis, L.
      donovani and L. infantum as well as their structure-activity relationship (SAR),
      molecular targets and in silico ADMET evaluation. In this way, it is expected
      that this review may support the research and development of new promising
      chalcones candidates a leishmanicidal drugs.

PMID- 29602039
TI  - Potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the
      benzoisoxazole moiety: application of a bioisosteric scaffold hopping approach to
      flufenamic acid.
AB  - The aldo-keto reductase 1C3 (AKR1C3) isoform plays a vital role in the
      biosynthesis of androgens and is considered an attractive target in prostate
      cancer (PCa). No AKR1C3-targeted agent has to date been approved for clinical
      use. Flufenamic acid and indomethacine are non-steroidal anti-inflammatory drugs
      known to inhibit AKR1C3 in a non-selective manner as COX off-target effects are
      also observed. Recently, we employed a scaffold hopping approach to design a new
      class of potent and selective AKR1C3 inhibitors based on a N-substituted
      hydroxylated triazole pharmacophore. Following a similar strategy, we designed a
      new series focused around an acidic hydroxybenzoisoxazole moiety, which was
      rationalised to mimic the benzoic acid role in the flufenamic scaffold. Through
      iterative rounds of drug design, synthesis and biological evaluation, several
      compounds were discovered to target AKR1C3 in a selective manner. The most
      promising compound of series (6) was found to be highly selective (up to 450
      fold) for AKR1C3 over the 1C2 isoform with minimal COX1 and COX2 off-target
      effects. Other inhibitors were obtained modulating the best example of
      hydroxylated triazoles we previously presented. In cell-based assays, the most
      promising compounds of both series reduced the cell proliferation, prostate
      specific antigen (PSA) and testosterone production in AKR1C3-expressing 22RV1
      prostate cancer cells and showed synergistic effect when assayed in combination
      with abiraterone and enzalutamide. Structure determination of AKR1C3 co
      crystallized with one representative compound from each of the two series clearly
      identified both compounds in the androstenedione binding site, hence supporting
      the biochemical data.

PMID- 29602040
TI  - Prevention and management of carcinoid crises in patients with high-risk
      neuroendocrine tumours undergoing peptide receptor radionuclide therapy (PRRT):
      Literature review and case series from two Australian tertiary medical
      institutions.
AB  - Peptide receptor radionuclide therapy (PRRT) is an important therapeutic option
      for somatostatin receptor (SSTR) positive metastatic and/or inoperable
      neuroendocrine tumours (NETs). However, in patients with poorly controlled
      carcinoid syndrome, it may lead to an acute flare of carcinoid symptoms or even
      carcinoid crisis. We report seven patients who received PRRT with (177Lu-DOTA0,
      Tyr3) octreotate (177Lu-octreotate-LuTate) across two Australian tertiary medical
      institutions who developed acute flare of carcinoid symptoms/carcinoid crisis
      during/after PRRT. Cases were identified as high-risk due to previous history of
      carcinoid crises, high tumour burden and markedly elevated tumour markers. We
      propose a protocol to prevent and manage severe carcinoid symptoms in high-risk
      patients treated with PRRT.

PMID- 29602042
TI  - LQTA-R: A new 3D-QSAR methodology applied to a set of DGAT1 inhibitors.
AB  - The rapid advances in computational methods for the drug design have resulted in
      the accurate predictions of biological activities of ligands with or without the
      availability of enzyme structures. 3D-QSAR is one of the computational methods
      used for such purpose. Currently, freely available 3D-QSAR methods suffer the
      limitations like complex methodologies, difficulty in the analysis of results,
      applying the statistical methods and validations of models built. Present work
      describes simple and novel 3D-QSAR methodology, which uses bash scripts
      LQTA_R_LJ, LQTA_R_QQ and LQTA_R_HB using freely available R statistical program.
      These scripts then generate Leenard-Jones, Coulomb and Hydrogen bond descriptors.
      These descriptors provide the steric 3D property, electrostatic property and
      hydrogen bond formation capacity respectively. These scripts have been tested for
      the set of DGAT1 inhibitors and results showed that the 3D-QSAR models built have
      better predictive abilities in terms of R2 0.735, Q2loo 0.635 and R2ext 0.715.
      The 3D-QSAR model suggested that the substitutions of the alkyl group at the
      oxadiazolyl ring at the 6th position of the pyrrolo-pyridazine ring is
      undesirable, on the contrary, substituted phenyl ring at 7th position is
      responsible for the improved DGAT1 inhibitory activity. The analysis also
      suggested that 6th position could be substituted with the oxadiazolyl ring or
      analogous heterocyclic rings, where the 3rd position of such heterocyclic rings
      substituted with rigid hydrophobic substitute can improve DGAT1 activity.

PMID- 29602041
TI  - Electrochemical immunosensor for highly sensitive and quantitative detection of
      tumor necrosis factor-alpha in human serum.
AB  - Highly sensitive and selective biosensors for accurate determination of specific
      protein biomarkers at low levels in serum are a prerequisite for the present
      healthcare systems. Therefore, here we developed a label-free impedimetric method
      for tumor necrosis factor-alpha (TNF-alpha) detection using reduced graphene
      oxide (RGO) with gold nanoparticles (AuNP) on an indium tin oxide (ITO) microdisk
      electrodes. The detection mechanism relies on resistance change occurs due to
      [Fe(CN)6]3-/4- redox probe movement towards the conductive channels of the AuNP
      RGO films gated by the recognition of the target biomarker by its anti-TNF-alpha
      antibody. The conductivity of the AuNP-RGO structures enhanced by 10-fold in
      comparison with bare electrode chips. The observed resistance changes at 2Hz
      (DeltaR at 2Hz) enabled the quantification of various concentrations of TNF-alpha
      in human serum (CHS-TNF-alpha). The antibody-adsorbed electrode showed a good
      increment of resistance change (DeltaR) with additions of antigen concentration.
      The sensor possesses a linear range of 1-1000pg/ml had a detection limit of
      0.67pg/ml (38.51fM) and 0.78pg/ml (44.83fM) in PBS and human serum, respectively.

PMID- 29602043
TI  - A survey of recently emerged genome-wide computational enhancer predictor tools.
AB  - The race for the discovery of enhancers at a genome-wide scale has been on since
      the commencement of next generation sequencing decades after the discovery of the
      first enhancer, SV40. A few enhancer-predicting features such as chromatin
      feature, histone modifications and sequence feature had been implemented with
      varying success rates. However, to date, there is no consensus yet on the single
      enhancer marker that can be employed to ultimately distinguish and uncover
      enhancers from the enormous genomic regions. Many supervised, unsupervised and
      semi-supervised computational approaches had emerged to complement and facilitate
      experimental approaches in enhancer discovery. In this review, we placed our
      focus on the recently emerged enhancer predictor tools that work on general
      enhancer features such as sequences, chromatin states and histone modifications,
      eRNA and of multiple feature approach. Comparisons of their prediction methods
      and outcomes were done across their functionally similar counterparts. We provide
      some recommendations and insights for future development of more comprehensive
      and robust tools.

PMID- 29602045
TI  - Chemoenzymatic synthesis of new derivatives of glycyrrhetinic acid with antiviral
      activity. Molecular docking study.
AB  - We present an efficient approach to the synthesis of a series of glycyrrhetinic
      acid derivatives. Six derivatives, five of them new compounds, were obtained
      through chemoenzymatic reactions in very good to excellent yield. In order to
      find the optimal reaction conditions, the influence of various parameters such as
      enzyme source, nucleophile:substrate ratio, enzyme:substrate ratio, solvent and
      temperature was studied. The excellent results obtained by lipase catalysis made
      the procedure very efficient considering their advantages such as mild reaction
      conditions and low environmental impact. Moreover, in order to explain the
      reactivity of glycyrrhetinic acid and the acetylated derivative to different
      nucleophiles in the enzymatic reactions, molecular docking studies were carried
      out. In addition, one of the synthesized compounds exhibited remarkable antiviral
      activity against TK + and TK- strains of Herpes simplex virus type 1 (HSV-1),
      sensitive and resistant to acyclovir (ACV) treatment.

PMID- 29602044
TI  - Effects of environmentally relevant sub-chronic atrazine concentrations on
      African clawed frog (Xenopus laevis) survival, growth and male gonad development.
AB  - Sub-chronic toxicity of environmentally relevant atrazine concentrations on
      exposed tadpoles and adult male African clawed frogs (Xenopus laevis) was
      evaluated in a quality controlled laboratory for 90 days. The aim of this study
      was to determine the effects of atrazine on the survival, growth and gonad
      development of African clawed frogs. After exposure of tadpoles to atrazine
      concentrations of 0 (control), 0.01, 200 and 500 MUg L-1 in water, mortality
      rates of 0, 0, 3.3 and 70% respectively were recorded for the 90 day exposure
      period. Morphometry showed significantly reduced tadpole mass in the 500 MUg L-1
      atrazine exposed tadpoles (p < 0.05). Light microscopy on testes of adult frogs
      exposed to the same atrazine concentrations using hematoxylin and eosin (H&E) and
      Van Gieson staining techniques revealed gonadal atrophy, disruption of germ cell
      lines, seminiferous tubule structure damage and formation of extensive connective
      tissue around seminiferous tubules of frogs exposed to 200 MUg L-1 and 500 MUg L
      1 atrazine concentrations. Ultrastructural analysis of the cellular organelles
      using transmission electron microscopy (TEM) revealed significant amounts of
      damaged mitochondria in testosterone producing Leydig cells as well as Sertoli
      cells. Biochemical analysis revealed reduced serum testosterone levels in adult
      frogs at all exposure levels as well as presence of six atrazine metabolites in
      frog serum and liver. The results indicate that atrazine concentrations greater
      than the calculated LC50 of 343.7 MUg L-1 cause significant mortality in
      tadpoles, while concentrations >=200 MUg L-1 adversely affect reproductive health
      of adult frogs and development of tadpoles sub-chronically exposed to atrazine.

PMID- 29602046
TI  - Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX
      inhibition profile of some novel quinoline derivatives.
AB  - New quinoline compounds comprising pyrazole scaffold through different amide
      linkages were synthesized. The synthesized compounds were evaluated for their
      anti-inflammatory activity. Eight compounds (5c, 11b,c, 12c, 14a,b, 20a and 21a)
      were found to exhibit promising anti-inflammatory profiles in acute and sub-acute
      inflammatory models. They were screened for their ulcerogenic activity and none
      of them showed significant ulcerogenic activity comparable to the reference drug
      celecoxib and are well tolerated by experimental animals with high safety margin
      (ALD50 > 0.3 g/kg). Compounds 5c, 11b,c, 12c, 14a,b, 20a and 21a showed
      significant in vitro LOX inhibitory activity higher than that of zileuton. In
      vitro COX-1/COX-2 inhibition study revealed that compounds 12c, 14a,b and 20a
      showed higher selectivity towards COX-2 than COX-1. Among the tested compounds,
      12c, 14a and 14b showed the highest inhibitory activity against COX-2 with an
      IC50 values of 0.1, 0.11 and 0.11 MUM respectively. The docking experiments
      attempted to postulate the binding mode for the most active compounds in the
      binding site of COX-2 enzymes and confirmed the high selectivity binding towards
      COX-2 enzyme over COX-1.

PMID- 29602047
TI  - Molecular characterization of Aspergillus fumigatus isolated from raw cow milk in
      Argentina: Molecular typing of A. fumigatus from raw cow milk.
AB  - Aspergillus fumigatus, the major etiological agent of human and animal
      aspergillosis, is a gliotoxinogenic species into section Fumigati commonly found
      in contaminated animal environments. In dairy herds, exposed areas of lactating
      cows, as mammalian glandule, can be easily contaminated by them. This study was
      aimed to identify A. fumigatus sensu lato strains (identified based on
      morphology) isolated from raw cow milk at species level, by morphological and
      molecular techniques, and to estimate their genetic variability. Forty-five A.
      fumigatus strains showed similar RAPD profiles (generated with PELF and URP1F
      primers) to each other and to A. fumigatus sensu stricto reference strains; also,
      they were almost identical to clinical human and feed-borne A. fumigatus strains
      included in the assay, since their similarity coefficient ranged from 0.7 to
      1.00. Therefore, all strains were characterized as belonging to A. fumigatus
      sensu stricto species. This result was supported by sequencing the benA gene of
      selected strains and by maximum parsimony analysis. In addition, RAPD
      fingerprinting demonstrated intra-specific genetic variability into the A.
      fumigatus sensu stricto cluster. The results found in this study strengthen the
      fact that A. fumigatus sensu stricto is the predominant species in the
      Aspergillus section Fumigati found in animal environments such as dairy herd
      environments, while other species such as A. novofumigatus, A. fumigatiaffinis,
      A. udagawae and A. lentulus may be rarely isolated. Since no differences between
      animal and human strains were observed they can become pathogenic also for farm
      handlers'. Moreover, the presence of A. fumigatus sensu stricto in raw cow milk
      is probably a very important risk factor since milk and its by-products are
      generally indented for human consumption, then gliotoxin could be transferred to
      them.

PMID- 29602048
TI  - Lymphoblast-derived integration-free iPSC line AD-TREM2-1 from a 67year-old
      Alzheimer's disease patient expressing the TREM2 p.R47H variant.
AB  - Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD)
      expressing the TREM2 p.R47H variant were used to generate integration-free
      induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids
      harbouring OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. AD-TREM2-1 was defined as
      pluripotent based on (i) expression of pluripotency-associated markers (ii)
      embryoid body-based differentiation into cell types representative of the three
      germ layers and (iii) the similarity between the transcriptome of the iPSC line
      and the human embryonic stem cell line H1 with a Pearson correlation of 0.947.

PMID- 29602049
TI  - Dynamic balance control during stair negotiation for older adults and people with
      Parkinson disease.
AB  - It is well understood that stability during ambulation is reliant upon
      appropriate control of the trunk segment, but research shows that the rhythmicity
      of this segment is significantly reduced for people with Parkinson's disease
      (PD). Given the increased risk associated with stair ambulation, this study
      investigated whether people with PD demonstrate poorer trunk control during stair
      ambulation compared with age-matched controls. Trunk accelerations were recorded
      for twelve PD patients and age-matched controls during stair ascent and descent.
      Accelerations were used to derive measures of harmonic ratios and root mean
      square (RMS) acceleration to provide insight into the rhythmicity and amplitude
      of segmental motion. Compared with what is typically seen during level-ground
      walking, gait rhythmicity during stair negotiation was markedly reduced for older
      adults and people with PD. Furthermore, both groups exhibited significantly
      poorer trunk movements during stair descent compared to stair ascent, suggesting
      that both populations may face a greater risk of falling during this task. As
      stair negotiation is a common activity of daily life, the increased risk
      associated with this task should be considered when working with populations that
      have an increased risk of falling.

PMID- 29602050
TI  - Position of pelvis in the 3rd month of life predicts further motor development.
AB  - The aim of the study is to select elements of motor skills assessed at 3 months
      that provide the best predictive properties for motor development at 9 months. In
      all children a physiotherapeutic assessment of the quantitative and qualitative
      development at the age of 3 months was performed in the prone and supine
      positions, which was presented in previous papers as the quantitative and
      qualitative assessment sheet of motor development. The neurological examination
      at the age of 9 months was based on the Denver Development Screening Test II and
      the evaluation of reflexes, muscle tone (hypotony and hypertony), and symmetry.
      The particular elements of motor performance assessment were shown to have
      distinct predictive value for further motor development (as assessed at 9
      months), and the pelvis position was the strongest predictive element.
      Irrespective of the symptomatic and anamnestic factors the inappropriate motor
      performance may already be detected in the 3rd month of life and is predictive
      for further motor development. The assessment of the motor performance should be
      performed in both supine and prone positions. The proper position of pelvis
      summarizes the proper positioning of the whole spine and ensures proper further
      motor development. To our knowledge, the presented motor development assessment
      sheet allows the earliest prediction of motor disturbances.

PMID- 29602051
TI  - Children who stutter at 3 years of age: A community-based study.
AB  - PURPOSE: Lack of social resources to support children who stutter may be due, in
      part, to the absence of epidemiological data regarding stuttering. This study
      investigated the proportion of three-year-old children who stutter in a city
      located in Hokkaido, a northern island of Japan. METHODS: The speech of
      individual children was assessed as part of a routine, government-conducted
      health care examination for 3-year-old children. The number of children screened
      was 2274, or 94.4% of all children in the city. The first author participated in
      the health care examination, and followed up all of the children who were found
      to stutter. RESULTS: At 3 years of age, 1.41% of the children exhibited
      stuttering; 82.8% of these children subsequently did not exhibit stuttering six
      months later. Boys were 1.57 times more likely to stutter than girls, but they
      had only 86% of the probability of reported or observed fluency seen in girls six
      months later. Significantly higher probability of later fluency was observed in
      children who exhibited normal, rather than delayed, language development at the
      1.5-year health checkup preceding the 3-year health checkup. CONCLUSION: The
      proportion of three-year-old children who stutter and fluency status 6 months
      later are reported for a large cohort of Japanese children in Hokkaido. Language
      skills at 1;6 year may potentially be a factor in natural recovery or
      persistence; because of limitations in our study design, this assumption requires
      additional study. This is the first preliminary study to determine the proportion
      of three-year-old children who stutter in a Japanese community.

PMID- 29602052
TI  - Comparison of adults who stutter with and without social anxiety disorder.
AB  - PURPOSE: Social anxiety disorder is a debilitating anxiety disorder associated
      with significant life impairment. The purpose of the present study is to evaluate
      overall functioning for adults who stutter with and without a diagnosis of social
      anxiety disorder. METHOD: Participants were 275 adults who stuttered (18-80
      years), including 219 males (79.6%) and 56 females (20.4%), who were enrolled to
      commence speech treatment for stuttering. Comparisons were made between
      participants diagnosed with social anxiety disorder (n = 82, 29.8%) and those
      without that diagnosis (n = 193, 70.2%). RESULTS: Although the socially anxious
      group was significantly younger than the non-socially anxious group, no other
      demographic differences were found. When compared to the non-socially anxious
      group, the socially anxious group did not demonstrate significantly higher self
      reported stuttering severity or percentage of syllables stuttered. Yet the
      socially anxious group reported more speech dissatisfaction and avoidance of
      speaking situations, significantly more psychological problems, and a greater
      negative impact of stuttering. CONCLUSION: Significant differences in speech and
      psychological variables between groups suggest that, despite not demonstrating
      more severe stuttering, socially anxious adults who stutter demonstrate more
      psychological difficulties and have a more negative view of their speech. The
      present findings suggest that the demographic status of adults who stutter is not
      worse for those with social anxiety disorder. These findings pertain to a
      clinical sample, and cannot be generalized to the wider population of adults who
      stutter from the general community. Further research is needed to understand the
      longer-term impact of social anxiety disorder for those who stutter.

PMID- 29602053
TI  - EEG findings and outcomes of continuous video-EEG monitoring started prior to
      initiation of seizure treatment in the perinatal stroke.
AB  - BACKGROUND: To analyze the findings in the background EEG activity of infants who
      suffered perinatal stroke. METHODS: Eleven neonates born 2009-2014 diagnosed of
      ischemic stroke by MRI (three of them with multistroke) underwent continuous
      video-EEG monitoring. Visual and spectral (power spectrum and coherence) analyses
      of the background EEG was performed in three moments: 1) Onset of EEG recording
      (prior to initiate seizure treatment), 2) Post-ictal epoch (1-2 h after the last
      seizure), and 3) one-two days after seizure control. All children aged 2-6 years
      underwent neurodevelopmental assessment. RESULTS: Discontinuity, asymmetry,
      asynchrony, transients, and relative power spectrum in delta and theta frequency
      bands increased significantly (p < 0.05) in the post-ictal epoch with respect to
      onset of EEG recording. After seizure control, discontinuity, asynchrony, and
      theta power spectrum no longer had significant differences with those found at
      onset of EEG recording. Significant differences between the ischemic and
      unaffected hemispheres were found in transients and in beta coherence (p = 0.002;
      p = 0.001, respectively) exclusively in the post-ictal epoch. Seizure burden and
      time-to-control ranged 5-38 min and 0.5-40 h respectively. Currently, only one
      child is affected by spastic monoparesis. The intelligence quotients ranged 96
      123. CONCLUSIONS: The background EEG can undergo significant changes in the post
      ictal epoch due to the seizure activity triggered by the perinatal stroke. Most
      of these EEG changes involve all brain activity and not exclusively the ischemic
      hemisphere. Many of these modifications in the EEG background reverse following
      the seizure control. Video-EEG monitoring allows accurate/immediate diagnosis and
      rapid/intensive treatment of the stroke-associated seizures.

PMID- 29602054
TI  - A novel single-step GC-MS/MS method for cannabinoids and 11-OH-THC metabolite
      analysis in hair.
AB  - THC, CBD, CBN, THC-COOH and 11-OH-THC are the most popular markers of cannabis
      consumption and abuse. The use of this drug is a serious social problem
      worldwide. In this study, a method based on gas chromatography-tandem mass
      spectrometry (GC-MS/MS) operated in electron ionization (EI) with simple and
      rapid liquid-liquid extraction (LLE) and derivatization was developed and
      validated for the simultaneous determination of THC, CBD, CBN and 11-OH-THC in
      hair samples. The detection of all compounds was based on multiple reaction
      monitoring (MRM) transitions. The most important advantage of this method is the
      single-step, quick, easy and effective sample extraction procedure for THC, CBD,
      CBN and 11-OH-THC. The method showed a good linearity with a correlation
      coefficient (r2) between 0.997 and 0.999 for all substances. The variation
      coefficient (%CV) was <5% for THC, 11-OH-THC and CBD and <13% for CBN. The limit
      of detection (LOD) was 0.03 pg/mg for 11-OH-THC and it ranged from 0.3 to 1.4
      pg/mg for THC, CBD and CBN. The limit of quantification was 0.1 pg/mg for 11-OH
      THC and it ranged from 0.9 to 4.7 pg/mg for THC, CBD and CBN. Analytical recovery
      was higher than 88% for 11-OH-THC and it ranged between 68 and 97% for THC, CBD
      and CBN. Intra- and inter-assay precision and accuracy were always lower than 9
      14% and 5-9%, respectively. In parallel, we have quantified the THC-COOH level,
      following the methods previously set-up by us. The whole procedure was
      successfully applied to more than 200 different hair samples from cannabis
      consumers, disclosing the presence of 11-OH-THC in a range between 0.2 pg/mg and
      27 pg/mg, and the presence of THC-COOH in a range between 0.05 pg/mg and 42.05
      pg/mg. These data provided a good start towards the use of 11-THC-OH as
      alternative hair biomarker of cannabis consumption.

PMID- 29602055
TI  - Optimization of a modified QuEChERS method for the determination of tetracyclines
      in fish muscle by UHPLC-MS/MS.
AB  - In this work a sample treatment based on a modified QuEChERS method combined with
      ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS) was proposed to determine the residues of five common tetracyclines in
      fish muscle samples. The separation was achieved in less than 4 min and the
      analytes were detected in electrospray ionization in positive mode (ESI+) with
      multiple reaction monitoring mode. Parameters affecting the extraction step, such
      as the amount of sample and EDTA-McIlvaine buffer and extraction solvent volumes,
      were optimized by means of experimental design. In order to obtain the lowest
      matrix effect, parameters affecting the clean-up step by dispersive solid phase
      extraction (dSPE), were also studied. Under optimum conditions, matrix effect was
      lower than ?15?% in all cases. Limits of quantification were lower than 4.4 MUg
      kg-1 for the compounds in the selected samples, being in compliance with the
      current legislation. The precision, expressed as relative standard deviation, was
      below 18.5% and the recoveries for fortified fish samples (salmon and panga)
      higher than 80%. These results revealed that the proposed method is simple,
      rapid, cheap and environmentally friendly, being successfully applicable for the
      determination of these residues in fish samples.

PMID- 29602056
TI  - Hydrophilic interaction liquid chromatography-tandem mass spectrometry method for
      the determination of intact oxaliplatin in cells: validated and applied in colon
      cancer HCT-116 cell line.
AB  - Oxaliplatin is a platinum compound that is frequently prescribed for the
      chemotherapeutic treatment of colorectal cancer. In tumor cells, cellular uptake
      is the first step of oxaliplatin action. Cellular accumulation of oxaliplatin is
      considered to play an important role in anti-cancer efficacy. However, limited
      information about cellular accumulation of intact oxaliplatin is available. In
      this study, a sensitive hydrophilic interaction liquid chromatography-tandem mass
      spectrometry (HILIC-MS/MS) approach for the quantification of oxaliplatin in
      cells was developed and validated. The method allowed for a rapid and simple
      determination of intact oxaliplatin in cell lysate. The retention time of
      oxaliplatin was 3.04 min, which was achieved by applying a chromatographic
      gradient elution of 5 min. The lower limit of quantification (LLOQ) was 2 ng/mL
      and the analytical range of oxaliplatin was linear between 2-200 ng/mL. The intra
      day precision and inter-day precision (RSD (relative standard deviation)) ranged
      from 0.52 to 7.89%, and the accuracy (RE (relative error)) was within +/- 4.5%.
      Matrix effects and recovery were acceptable. The method was successfully used for
      the determination of intact oxaliplatin uptake by HCT-116 colon cancer cells.
      Thus, our findings may prospectively support a celluar pharmacokinetic study and
      low concentration measurement of intact oxaliplatin in the clinic.

PMID- 29602057
TI  - Structure and chemistry of interfaces between ceria and yttria-stabilized
      zirconia studied by analytical STEM.
AB  - Epitaxial undoped and Gd2O3-doped ceria films were grown by pulsed laser
      deposition on (1 1 1) faced Y2O3-stabilized zirconia (YSZ). Highly localized
      cerium reduction at the film-substrate interfaces is revealed by atomically
      resolved valence EELS mapping using Cs aberration-corrected scanning transmission
      electron microscopy. The chemical profiles reveal interdiffusion of Ce, (Gd), Y,
      Zr, forming an intermixing zone at the interface 7-9 (1 1 1) lattice planes wide.
      In its vicinity, the fraction of Ce3+ raises gradually over 6-8 lattice planes
      from zero in the bulk ceria to ~100% in one single plane at the interface. Beyond
      this plane the Ce3+ fraction drops sharply within the YSZ substrate. In the
      vicinity of the interface systematic scan deflections are observed during EELS
      line scans. The advancing electron probe experiences a retarding force at the
      ceria side, and an accelerating force at the YSZ side, irrespective of the scan
      direction. This behavior is suggestive of coulombic interactions between the
      electron probe and a charged interface. This is interpreted as an indication of
      the presence of a space-charge situation at the YSZ/ceria interface, resulting
      from an excess negative charge at the ceria side (due to Ce3+cations) and an
      excess positive charge at the YSZ side (due to oxygen vacancies).

PMID- 29602058
TI  - Cell mechanics of pollen tube growth.
AB  - The pollen tube features particular traits that can only be understood when
      integrating cell biological with cell mechanical concepts. Firstly, regular
      temporal variations in the growth rate are governed by a feedback mechanism
      thought to involve mechanosensitive ion channels. Secondly, the tube uses
      invasive growth to penetrate the flower tissues with the aim to transport the
      male sperm cells to their target. Thirdly, the pollen tube is able to reorient
      its growth direction upon exposure to a guidance cue; the steering mechanism
      involves the sophisticated choreography of intracellular transport processes.
      Sophisticated imaging and micromanipulation techniques have been instrumental for
      the advancement in characterizing the biomechanical features of this crucial cell
      in the plant reproductive cycle.

PMID- 29602059
TI  - Evaluation of particulate 137Cs discharge from a mountainous forested catchment
      using reservoir sediments and sinking particles.
AB  - The time and size dependencies of particulate 137Cs concentrations in a reservoir
      were investigated to evaluate the dynamics of 137Cs pollution from a mountainous
      forested catchment. Sediment and sinking particle samples were collected using a
      vibracorer and a sediment trap at the Ogaki Dam Reservoir in Fukushima, which is
      located in the heavily contaminated area that formed as a result of the Fukushima
      Dai-ichi Nuclear Power Plant accident of 2011. The inventory of 137Cs discharged
      into the reservoir during the post-accident period (965 days) was estimated to be
      approximately 3.0 * 1012-3.9 * 1012 Bq, which is equivalent to 1.1%-1.4% of the
      initial estimated catchment inventory. The particulate 137Cs concentration showed
      a decline with time, but the exponent value between the specific surface area and
      the 137Cs concentration for the fine-sized (<63 MUm) particle fraction remained
      almost constant from the immediate aftermath of the accident. These quantitative
      findings obtained by reconstructing the contamination history of particulate
      137Cs in reservoir sediments and sinking particles have important implications
      for the evaluation of 137Cs dynamics in mountainous forested catchments.

PMID- 29602060
TI  - Central bank interest rate decisions, household indebtedness, and psychiatric
      morbidity and distress: Evidence from the UK.
AB  - BACKGROUND: Central banks set economy-wide interest rates to meet exclusively
      economic objectives. There is a strong link between indebtedness and psychiatric
      morbidity at the individual level, with interest rates being an important factor
      determining ability to repay debt. However, no prior research has explored
      whether central bank interest rate changes directly influence mental health, nor
      whether this varies by levels of indebtedness. METHODS: We use British data (N =
      93,255) to explore whether the Bank of England base-rate affected how perceived
      burden of non-mortgage debt (low, medium, and high) influenced psychiatric
      morbidity. Psychiatric morbidity was measured using the General Health
      Questionnaire (GHQ-12). Our primary outcome measure was a binary indicator of
      "psychiatric caseness" (>3 on a 0-12 scale). We also used the GHQ-12 as a
      continuous measure of distress. RESULTS: When interest rates are high (low) there
      is an increased (decreased) risk of psychiatric morbidity only among those with a
      high debt burden (b = 0.026, p =  0.02). This result was robust to alternative
      explanations. Thus a 1 percentage point base-rate increase is associated with a
      2.6% increase that someone with a high debt burden will experience psychiatric
      morbidity. LIMITATIONS: Our study uses subjective indicators of debt burden. We
      were unable to determine the mechanism behind our effect. CONCLUSIONS: Changes in
      central bank interest rates to meet economic objectives pose a threat to mental
      health. Mental health support is needed for those in debt and central banks may
      need to consider how their decisions influence population mental health.

PMID- 29602061
TI  - Enhanced DNA mixture deconvolution of sexual offense samples using the DEPArrayTM
      system.
AB  - The interpretation of DNA mixtures remains a significant challenge in the
      analysis of forensic evidence. The ability to selectively identify, collect, and
      analyze single cells or groups of cells has wide implications in the analysis of
      forensic samples and the subsequent deconvolution of DNA mixtures, particularly
      in the processing and interpretation of sexual offense evidence where the
      deconvolution of heterogeneous sources is essential. Single cell separation
      technology can be used to address this mixture separation challenge, specifically
      using the DEPArrayTM system from Menarini Silicon Biosystems. We propose that the
      DEPArrayTM will enable enhancements to the standard workflow for forensic
      biology/DNA analytical laboratories. We have demonstrated that the DEPArrayTM
      workflow will lead to fewer mixture samples, enable purification of sperm and
      epithelial cell fractions without the need for differential extraction, improve
      the amplification success rate of samples and improve the interpretation of low
      template DNA samples. Sperm profiles were identified in 27 of 32 DEPArrayTM
      processed samples, with 26 of 27 (96.2%) yielding single source profiles. In
      contrast, single source profiles were obtained from 9 of 28 (32.1%)
      differentially extracted samples. The use of the DEPArrayTM also eliminates the
      need for additional confirmatory tests for the presence of human sperm and
      permits direct identification of the type and number of cells being analyzed
      eliminating the need for qPCR-based DNA quantification.

PMID- 29602062
TI  - Reported credibility techniques in higher education evaluation studies that use
      qualitative methods: A research synthesis.
AB  - This synthesis study examined the reported use of credibility techniques in
      higher education evaluation articles that use qualitative methods. The sample
      included 118 articles published in six leading higher education evaluation
      journals from 2003 to 2012. Mixed methods approaches were used to identify key
      credibility techniques reported across the articles, document the frequency of
      these techniques, and describe their use and properties. Two broad sets of
      techniques were of interest: primary design techniques (i.e., basic), such as
      sampling/participant recruitment strategies, data collection methods, analytic
      details, and additional qualitative credibility techniques (e.g., member
      checking, negative case analyses, peer debriefing). The majority of evaluation
      articles reported use of primary techniques although there was wide variation in
      the amount of supporting detail; most of the articles did not describe the use of
      additional credibility techniques. This suggests that editors of evaluation
      journals should encourage the reporting of qualitative design details and authors
      should develop strategies yielding fuller methodological description.

PMID- 29602063
TI  - Wandering spleen with horseshoe kidney a rare occurrence.
AB  - INTRODUCTION: Wandering spleen is a rare clinical entity in itself, with only 2
      cases reported thus far when correlated with congenital under-development of the
      kidney, it usually happens due to under development of its surrounding ligaments.
      Herein we present a case of wandering spleen with underlying congenital deformity
      of horseshoe kidney which requires splenectomy due to late presentation.
      PRESENTATION OF CASE: A 21 year old lady presented with worsening of chronic
      abdominal pain for 3 years, associated with nausea and vomiting. Physical
      examination showed a vague mass located at epigastric region. Consecutively,
      computed tomography images showed a well-defined, oval, hypoechoic spleen
      extending from center of abdomen up to epigastric region measuring 15.5 * 13 cm
      with twisted pedicle. Finally the patient underwent surgical treatment. The
      intraoperative findings were consistent with computed tomography images. The
      patient made a full recovery and was discharged well. DISCUSSION: Wandering
      Spleen was first described by Van Horne during autopsy back in 1667. Its location
      is maintained by peritoneal attachments such as lienorenal, splenocolic,
      splenophrenic, gastrosplenic and phrenicocolic ligaments. Among which, the
      gastrosplenic ligament and lienorenal ligaments are of greatest significance.
      Patient with a wandering spleen may present asymptomatic, with a movable mass in
      the abdomen, or with chronic or intermittent abdominal pain because of partial
      torsion and spontaneous de-torsion of the spleen as in our case. When feasible
      especially in young patients, splenopexy should always be the first consideration
      but however if gross infarct has occurred then splenectomy is inevitable to save
      the patient. CONCLUSION: Wandering spleen is a unique surgical entity moreover
      when appeared in congruence with horseshoe kidney. Its diagnosis should be made
      in prompt to prevent splenic infarction and to try to salvage with splenopexy
      especially in younger population. However in patient where splenic torsion with
      infarction has occurred, splenectomy would be the treatment of choice.

PMID- 29602065
TI  - Targeting histone demethylases KDM5A and KDM5B in AML cancer cells: A comparative
      view.
AB  - Epigenetic modifications play an important role in initiation and progression of
      cancers including acute myeloid leukemia. Among different epigenetic modifiers,
      lysine specific demethylases have been noticed as potential therapeutic targets.
      KDM5 family of histone demethylases which removes methyl marks from lysine
      residues of H3, are frequently found in the promoter region of transcriptionally
      active genes resulting in repression of expression. Here we have compared the
      effects of KDM5A and KDM5B downregulation on HL-60 cell line behavior. KDM5A/5B
      knockdown resulted in lower viability of HL-60 cells in addition to modified cell
      cycle distribution and sub-G1 accumulation. Induction of apoptosis was observed
      in both knockdown cells. But in spite of similarity in their role, downregulation
      of KDM5A showed more efficient anti-leukemic effects in comparison to KDM5B.
      Cells showed higher accumulation in sub-G1 and apoptosis occurred significantly
      higher and also earlier after KDM5A reduction. Expression analysis confirmed
      almost 5 and 4 fold increased expression for bax and caspase-3 after
      downregulation of KDM5A in comparison to KDM5B. Due to the present study we
      propose KDM5A as a potential target for therapeutic aspects of acute myeloid
      leukemia although further investigations are needed.

PMID- 29602064
TI  - High-throughput Cos-Seq screen with intracellular Leishmania infantum for the
      discovery of novel drug-resistance mechanisms.
AB  - Increasing drug resistance towards first line antimony-derived compounds has
      forced the introduction of novel therapies in leishmaniasis endemic areas
      including amphotericin B and miltefosine. However, their use is threatened by the
      emergence and spread of drug-resistant strains. In order to discover stage
      dependent resistance genes, we have adapted the Cos-Seq approach through the
      introduction of macrophage infections in the pipeline. A L. infantum
      intracellular amastigote population complemented with a L. infantum cosmid
      library was submitted to increasing concentrations of miltefosine, amphotericin B
      and pentavalent antimonials in experimental infections of THP-1 cells. For each
      step of selection, amastigotes were extracted and cosmids were isolated and
      submitted to next-generation sequencing, followed by subsequent gene-enrichment
      analyses. Cos-Seq screen in amastigotes revealed four highly enriched loci for
      antimony, five for miltefosine and one for amphotericin B. Of these, a total of
      seven cosmids were recovered and tested for resistance in both promastigotes and
      amastigotes. Candidate genes within the pinpointed genomic regions were validated
      using single gene overexpression in wild-type parasites and/or gene disruption by
      means of a CRISPR-Cas9-based approach. This led to the identification and
      validation of a stage-independent antimony-resistance gene (LinJ.06.1010) coding
      for a putative leucine rich repeat protein and a novel amastigote-specific
      miltefosine-resistance gene (LinJ.32.0050) coding for a member of the SEC13
      family of WD-repeat proteins. This study further reinforces the power of Cos-Seq
      approach to discover novel drug-resistance genes, some of which are life-stages
      specific.

PMID- 29602066
TI  - New synergistic combinations of differentiation-inducing agents in the treatment
      of acute promyelocytic leukemia cells.
AB  - Acute promyelocytic leukemia (APL) was considered to be one of the most lethal
      forms of leukemia in adults before the introduction of the vitamin A metabolite
      all-trans retinoic acid (ATRA). Surprisingly, it has been confirmed that FICZ (6
      Formylindolo (3, 2-b) carbazole) enhances ATRA-induced differentiation. Moreover,
      a number of studies have demonstrated that anti CD44 monoclonal antibody (mAb)
      induces to bring back differentiation blockage the leukemic stem cells. The level
      of differentiation markers including CD11b and CD11c in NB4 cells was assessed by
      flow cytometry. The induction of apoptosis was also evaluated. We estimated the
      induction potential of a triple compound of ATRA-FICZ, anti-CD44 maps. The cells
      showed the gradually increased expression levels of CD11b and CD11c. A mixture of
      a "CD44 mAb, ATRA and FICZ effectively promoted granulocytic maturation resulting
      in increased rates of apoptosis. The differences in expression of CD11b and CD11c
      at 5 MUg/ml and 10 MUg/ml were significant. These phenomena were highest at 10
      MUg/ml CD44 mAb concentrations. Synergistic induction differentiation and
      apoptosis of APL cells by using a co-treatment with novel triple compound are
      more effective for eradicating blasts and controlling the metastasis. Our results
      show that the addition of anti-CD44 mAb improves "ATRA-FICZ"-induced
      differentiation and has potential to reduce usual chemotherapy based treatments.
      Taken together, this compound may lead to novel clinical applications of
      differentiation-based approaches for APL and other types of leukemia. Further
      clinical studies would be recommended to clarify the clinical efficacy.

PMID- 29602067
TI  - The use of computed tomography in the diagnosis of abdominal cocoon.
AB  - BACKGROUND: Literature on the diagnosis of abdominal cocoon using computed
      tomography (CT) outside the setting of continuous ambulatory peritoneal dialysis
      is sparse. METHODS: We did a retrospective analysis of contrast enhanced CT done
      for patients treated for abdominal cocoon. The clinical features, radiological
      findings, underlying etiology and outcomes were recorded. RESULTS: Of the 22
      patients analyzed, 19 had tuberculosis, 2 had malignancy and 1 was idiopathic.
      The basis of diagnosis of cocoon was CT in 18 and CT and surgery in 4. Types 1, 2
      and 3 cocoon were found in 3 (13.63%), 6 (27.27%) and 13 (59.09%) respectively.
      The bowel findings were clumped loops in 21 (95%), inter-bowel fluid in 13 (59%),
      bowel wall thickening/enhancement in 6 (27%) and stricture in 1 (5%). Peritoneal
      thickening and nodularity were seen in 14 (64%) and 2 (9%) while omental
      thickening, nodularity and mass in 9 (41%), 5 (21%) and 1 (5%). Cauliflower sign
      was seen in 14 (64%), concertina pattern in 5 (23%) and Bottle Gourd sign in 6
      (23%) patients. Of 12 with imaging done during episode of IO, 11 (92%) had
      cauliflower sign, 4 (80%) had concertina appearance and 6 (100%) had bottle gourd
      sign. Post treatment weight gain with anti-tubercular therapy was seen in 14
      (63.63%), resolution of ascites in 12 (54.54%) and 2 patients had complete
      resolution of cocoon on repeat imaging. CONCLUSION: CT is a valuable tool for pre
      operative diagnosis of abdominal cocoon. The classical described signs are seen
      more frequently in patients with IO.

PMID- 29602069
TI  - A set of autosomal multiple InDel markers for forensic application and population
      genetic analysis in the Chinese Xinjiang Hui group.
AB  - In recent years, insertion/deletion (InDel) markers have become a promising and
      useful supporting tool in forensic identification cases and biogeographic
      research field. In this study, 30 InDel loci were explored to reveal the genetic
      diversities and genetic relationships between Chinese Xinjiang Hui group and the
      25 previously reported populations using various biostatistics methods such as
      forensic statistical parameter analysis, phylogenetic reconstruction, multi
      dimensional scaling, principal component analysis, and STRUCTURE analysis. No
      deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in the
      Chinese Xinjiang Hui group. The observed heterozygosity and expected
      heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD92), 0.2222 (HLD118) to
      0.5000 (HLD6), respectively. The cumulative probability of exclusion and combined
      power of discrimination were 0.988849 and 0.99999999999378, respectively, which
      indicated that these 30 loci could be qualified for personal identification and
      used as complementary genetic markers for paternity tests in forensic cases. The
      results of present research based on the different methods of population genetic
      analysis revealed that the Chinese Xinjiang Hui group had close relationships
      with most Chinese groups, especially Han populations. In spite of this, for a
      better understanding of genetic background of the Chinese Xinjiang Hui group,
      more molecular genetic markers such as ancestry informative markers, single
      nucleotide polymorphisms (SNPs), and copy number variations will be conducted in
      future studies.

PMID- 29602070
TI  - Microbial degradation of Cold Lake Blend and Western Canadian select dilbits by
      freshwater enrichments.
AB  - Treatability experiments were conducted to determine the biodegradation of
      diluted bitumen (dilbit) at 5 and 25  degrees C for 72 and 60 days, respectively.
      Microbial consortia obtained from the Kalamazoo River Enbridge Energy spill site
      were enriched on dilbit at both 5 (cryo) and 25 (meso) oC. On every sampling day,
      triplicates were sacrificed and residual hydrocarbon concentrations (alkanes and
      polycyclic aromatic hydrocarbons) were determined by GCMS/MS. The composition and
      relative abundance of different bacterial groups were identified by 16S rRNA gene
      sequencing analysis. While some physicochemical differences were observed between
      the two dilbits, their biodegradation profiles were similar. The rates and extent
      of degradation were greater at 25  degrees C. Both consortia metabolized 99.9% of
      alkanes; however, the meso consortium was more effective at removing aromatics
      than the cryo consortium (97.5 vs 70%). Known hydrocarbon-degrading bacteria were
      present in both consortia (Pseudomonas, Rhodococcus, Hydrogenophaga,
      Parvibaculum, Arthrobacter, Acidovorax), although their relative abundances
      depended on the temperatures at which they were enriched. Regardless of the
      dilbit type, the microbial community structure significantly changed as a
      response to the diminishing hydrocarbon load. Our results demonstrate that dilbit
      can be effectively degraded by autochthonous microbial consortia from sites with
      recent exposure to dilbit contamination.

PMID- 29602068
TI  - Ectromelia virus lacking the E3L ortholog is replication-defective and
      nonpathogenic but does induce protective immunity in a mouse strain susceptible
      to lethal mousepox.
AB  - All known orthopoxviruses, including ectromelia virus (ECTV), contain a gene in
      the E3L family. The protein product of this gene, E3, is a double-stranded RNA
      binding protein. It can impact host range and is used by orthopoxviruses to
      combat cellular defense pathways, such as PKR and RNase L. In this work, we
      constructed an ECTV mutant with a targeted disruption of the E3L open reading
      frame (ECTVDeltaE3L). Infection with this virus resulted in an abortive
      replication cycle in all cell lines tested. We detected limited transcription of
      late genes but no significant translation of these mRNAs. Notably, the
      replication defects of ECTVDeltaE3L were rescued in human and mouse cells lacking
      PKR. ECTVDeltaE3L was nonpathogenic in BALB/c mice, a strain susceptible to
      lethal mousepox disease. However, infection with ECTVDeltaE3L induced protective
      immunity upon subsequent challenge with wild-type virus. In summary, E3L is an
      essential gene for ECTV.

PMID- 29602071
TI  - (Ce-Al)-oxide pillared bentonite: A high affinity sorbent for plutonium.
AB  - The ability of bentonite and montmorillonite pillared by Al-oxide and mixed (Ln
      Al)-oxides (Ln = La, Ce) to remove 239plutonium solution species from water is
      comparatively investigated at pH 7 and pH 4. Small-angle scattering and neutron
      contrast variation with H2O/D2O mixtures is used to verify the ingress of water
      in the calcined products after hydrophilicity was introduced by an NH3-H2O vapor
      treatment. The size and shape of the (La/Ce)-Al oxo-hydroxy pillaring cations (2
      nm spheres) is determined by small-angle x-ray scattering from the pillaring
      solutions. Not all of the oxide pillars improved Pu uptake compared with sodium
      montmorillonite. At neutral and acidic pH only (Ce-Al)-oxide pillared clays
      showed the ability to remove Pu over the concentration range studied (1.35 * 10-8
      8 * 10-8 mol dm-3) with distribution coefficient (KD) values >104. XPS analysis
      of the (Ce-Al)-oxide pillared clays indicates the presence of Ce4+ as cerium
      dioxide. The progressive improvement in sorption performance in the order of
      pillar type Al2O3 < La2O3-Al2O3 << CeO2-Al2O3 reflects the increasing access of
      Pu solution species to the clay mineral layers by changes to the basal spacing
      and specific surface area, and also to the higher stability of the (Ce-Al)-oxide
      pillars.

PMID- 29602072
TI  - Sex-related responses of European aspen (Populus tremula L.) to combined stress:
      TiO2 nanoparticles, elevated temperature and CO2 concentration.
AB  - The combined effects of climate change and chemical contaminants on plant
      performance are still not well understood. Especially, whether different sexes of
      dioecious plants respond differently to combined stresses is unknown. In order to
      study the sex-related responses of European aspen to soil nTiO2 contamination (0,
      50, 300 mg kg-1) under elevated temperature (+1.6  degrees C) and CO2 (730 ppm),
      we conducted a study in greenhouses. Ti accumulated in roots exposed to nTiO2
      (1.1-3.3 and 2.7-21.1 mg kg-1 in 50 and 300 mg kg-1 treatments, respectively).
      Elevated CO2 had no effects on Ti uptake, while elevated temperature increased it
      in the 300 mg kg-1 treatment. Males grew taller than females under ambient
      conditions, but females had greater height and biomass increment under elevated
      temperature. In all climate treatments, nTiO2 increased leaf phenolics in females
      by 12-19% and 15-26% at 50 and 300 mg kg-1, respectively. Leaf phenolics
      decreased under elevated temperature, but increased under elevated CO2 in both
      sexes. Results suggest that females have better chemical defense against nTiO2
      than males under future climate conditions. In the longer run, this may cause
      changes in the competitive abilities of both sexes, which again may affect sex
      ratios and genetic variation in nature.

PMID- 29602073
TI  - Role of IL-1beta, IL-6 and TNF-alpha cytokines and TNF-alpha promoter variability
      in Plasmodium vivax infection during pregnancy in endemic population of
      Jharkhand, India.
AB  - BACKGROUND: The combinatorial effects of Plasmodium infection, perturbation of
      inflammatory responses and the dichotomic role of TNF promoter polymorphism has
      potential clinical and physiological relevance during pregnancy. OBJECTIVE AND
      METHODS: This coordinated orchestration instigated us to investigate the
      circulating level of inflammatory cytokines (IL-1beta, TNF-alpha and IL-6)
      employing ELISA in a stratified group of samples and the plausible genetic
      association of TNF-alpha -308 G/A using PCR-RFLP/sequencing during Plasmodium
      vivax infection in pregnancy. RESULTS: We observed significantly elevated
      concentrations of IL-1beta were observed, followed by IL-6 and TNF-alpha in women
      with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1beta,
      followed by TNF-alpha and IL-6 were detected in the non-infected pregnancy group.
      The differential dynamics of inflammatory cytokine concentration during each
      trimester of pregnancy with and without P. vivax infection were detected. For the
      first time, a high level of IL-6 was observed in the first trimester of MIP and
      high IL-1beta in healthy pregnancies. In the second trimester, however, we
      observed a high level of IL-1beta in the MIP group compared to a sustained high
      level of IL-1beta in the healthy pregnancy group. In the third trimester, high IL
      1beta was sustained in the MIP group and healthy pregnancies acquired a high TNF
      alpha level. The genotypic distribution for the TNF-alpha promoter -308 G/A
      position was observed to be nonsignificant and mildly associated during MIP (OR =
      1.4) and in WWM (OR = 1.2). Moreover, based on genotypic distribution, we
      observed a well-correlated and significantly elevated TNF-alpha concentration in
      the mutant homozygote genotype (AA; p = 0.001) followed by heterozygotes (GA; p =
      0.0001) and ancestral genotypes (GG; p = 0.0001) in both MIP and WWM subjects.
      CONCLUSION: The observation of elevated IL-1beta and IL-6 in MIP and TNF-alpha in
      WWM may be regarded as a prognostic inflammatory marker of infection and
      pregnancy. Most particularly, the TNF-alpha concentration and its polymorphic
      variability in the promoter region may indicate genetic susceptibility and mildly
      influence the risk for P. vivax infection during pregnancy and in women with
      malaria.

PMID- 29602074
TI  - A review on acrylic based hydrogels and their applications in wastewater
      treatment.
AB  - The acrylic based hydrogels have attracted the attention of many researchers in
      the field of pollutants adsorption such as dyes and metal cations due to their
      high swelling and adsorption capacities. This review introduces acrylic based
      hydrogels and focuses on their adsorption properties. We first described the
      methods for synthesizing hydrogels. Usual methods of characterization of acrylic
      based hydrogels such as swelling, adsorption capacity and desorption efficiency
      of the pollutants have been investigated. In addition, the adsorption isotherm
      and kinetic models which determine the mechanism of pollutants' adsorption by
      hydrogels have been introduced and relations that determine the values of
      thermodynamic parameters which define accomplishment of adsorption process have
      been investigated. In the following sections, a perfect insight has been provided
      on natural and synthetic acrylic based hydrogels. The effective parameters of
      swelling and adsorption by acrylic based hydrogels have been reviewed and the
      mechanism of pollutant's adsorption by acrylic based hydrogels has been
      discussed.

PMID- 29602075
TI  - An Information System for Brownfield Regeneration: providing customised
      information according to stakeholders' characteristics and needs.
AB  - In the EU brownfield presence is still considered a widespread problem. Even
      though, in the last decades, many research projects and initiatives developed a
      wealth of methods, guidelines, tools and technologies aimed at supporting
      brownfield regeneration. However, this variety of products had and still has a
      limited practical impact on brownfield revitalisation success, because they are
      not used in their entire potential due to their scarce visibility. Also, another
      problem that stakeholders face is finding customised information. To overcome
      this non-visibility and not-sufficient customisation of information, the
      Information System for Brownfield Regeneration (ISBR) has been developed, based
      on Artificial Neural Networks, which allows understanding stakeholders'
      information needs by providing tailored information. The ISBR has been tested by
      stakeholders from the EU project TIMBRE case studies, located in the Czech
      Republic, Germany, Poland and Romania. Data gained during tests allowed to
      understand stakeholders' information needs. Overall, stakeholders showed to be
      concerned first on remediation aspects, then on benchmarking information, which
      are valuable to improve practices in the complex field of brownfield
      regeneration, and then on the relatively new issue of sustainability applied to
      brownfield regeneration and remediation. Mature markets confirmed their interest
      for remediation-related aspects, highlighting the central role that risk
      assessment plays in the process. Emerging markets showed to seek information and
      tools for strategic and planning issues, like brownfield inventories and
      georeferenced data sets. Results led to conclude that a new improved platform,
      combining the ISBR functionalities with geo-referenced ones, would be useful and
      could represent a further research application.

PMID- 29602076
TI  - Evaluation of physicochemical properties of radioactive cesium in municipal solid
      waste incineration fly ash by particle size classification and leaching tests.
AB  - After the Fukushima Daiichi-Nuclear Power Plant accident, environmental recovery
      was a major issue because a considerable amount of municipal solid waste
      incineration (MSWI) fly ash was highly contaminated with radioactive cesium. To
      the best of our knowledge, only a few studies have evaluated the detailed
      physicochemical properties of radioactive cesium in MSWI fly ash to propose an
      effective method for the solidification and reuse of MSWI fly ash. In this study,
      MSWI fly ash was sampled in Fukushima Prefecture. The physicochemical properties
      of radioactive cesium in MSWI fly ash were evaluated by particle size
      classification (less than 25, 25-45, 45-100, 100-300, 300-500, and greater than
      500 MUm) and the Japanese leaching test No. 13 called "JLT-13". These results
      obtained from the classification of fly ash indicated that the activity
      concentration of radioactive cesium and the content of the coexisting matter
      (i.e., chloride and potassium) temporarily change in response to the particle
      size of fly ash. X-ray diffraction results indicated that water-soluble
      radioactive cesium exists as CsCl because of the cooling process and that
      insoluble cesium is bound to the inner sphere of amorphous matter. These results
      indicated that the distribution of radioactive cesium depends on the
      characteristics of MSWI fly ash.

PMID- 29602078
TI  - Increasing the anticancer performance of bufalin (BUF) by introducing an endosome
      escaping polymer and tumor-targeting peptide in the design of a polymeric
      prodrug.
AB  - A well-defined multifunctional brush-type polymeric prodrug covalently linked
      with an anticancer drug (bufalin, BUF), a tumor-targeting peptide (RGD), and an
      endosome-escaping polymer, poly(N,N-diethylaminoethyl methacrylate-co-butyl
      methacrylate (P(DEA-co-BMA)), was developed. Its anticancer performance against
      colon cancer was investigated in vitro and in vivo. Reversible addition
      fragmentation transfer (RAFT) polymerization of oligo(ethylene glycol) monomethyl
      ether methacrylate (OEGMA), 2-((3-(tert-butoxy)-3-oxopropyl)thio)ethyl
      methacrylate (BSTMA), and 2-(2-bromoisobutyryloxy)ethylmethacrylate (BIEM)
      afforded the multifunctional random copolymer, P(OEGMA-co-BSTMA-co-BIEM), in
      which hydrophilic POEGMA can stabilize nanoparticles in water, PBSTMA can be
      converted into carboxyl groups, and PBIEM can be employed as a macromolecular
      atom radical transfer polymerization (ATRP) initiator. The ATRP of DEA and BMA
      using P(OEGMA-co-BSTMA-co-BIEM) as a macromolecular ATRP initiator led to the
      formation of the pH-responsive brush-type copolymer, P(OEGMA-co-BSTMA)-g-P(DEA-co
      BMA). After hydrolysis by trifluoroacetic acid and post-functionalization the
      final polymeric prodrug, P(OEGMA-co-BUF-co-RGD)-g-P(DEA-co-BMA), was obtained
      with a drug content of ~7.8 wt%. P(OEGMA-co-BUF-co-RGD)-g-P(DEA-co-BMA) can be
      assembled into nanoparticles (BUF- NP-RGD) in aqueous solution with a diameter of
      148.4 +/- 0.7 nm and a zeta potential of -7.6 +/- 0.4 mV. BUF-NP-RGD exhibited
      controlled drug release in the presence of esterase. Additionally, P(OEGMA-co-
      BSMA)-g-P(DEA-co-BMA) showed a significant hemolysis effect at a pH comparable to
      that of endosomes/lysosomes. Cell viability and a tumor-bearing nude mouse model
      were employed to evaluate the anticancer efficacy of BUF-NP-RGD. It was revealed
      that BUF-NP-RGD showed improved anticancer performance compared with that of free
      BUF both in vitro and in vivo. Histological and immunochemical analysis further
      demonstrated that BUF-NP-RGD exhibited improved cell apoptosis, angiogenesis
      inhibition, and an anti-proliferation effect.

PMID- 29602077
TI  - Dual alginate-lipid nanocarriers as oral delivery systems for amphotericin B.
AB  - Amphotericin B (AmB) is the first-choice drug to treat several fungal infections.
      However, due to its low solubility it can only be administrated intravenously.
      Nanostructured lipid carriers (NLC) have the ability to encapsulate hydrophobic
      drugs in an aqueous matrix, making them interesting for use in alternative drug
      delivery systems for AmB. Their combination with stimuli-sensitive polymers such
      as alginate can be used as a strategy to protect acid sensitive molecules from
      gastric acid. The proposal of this work was to develop a dual-strategy
      hydrogel/NLC delivery system for amphotericin B. NLCs were produced by high
      pressure homogenization and their size and stability were assessed by dynamic
      light scattering and electron transmission microscopy. The NLCs presented low
      cytotoxicity and high selectivity at neutral pH. Alginate hydrogels were
      successfully produced by the ionic gelation method and characterized using
      optical microscopy. The hydrogels were tested for their pH-selectivity,
      cytotoxicity and drug delivery profile. Swelling degree and drug delivery
      profiles suggested that drug delivery is stimulated as the alginate particles
      swell and that NLC particles maintain their structure even after rehydration,
      indicating these systems can be used for oral delivery of AmB.

PMID- 29602079
TI  - A novel and ultrasensitive electrochemical DNA biosensor based on an ice crystals
      like gold nanostructure for the detection of Enterococcus faecalis gene sequence.
AB  - Bacteria, parasites and viruses are found widely in the environment as potential
      pathogens, and can be the source of infections. Therefore, sensitive and rapid
      methods for identification of the pathogens are required to achieve a better
      quality of life. Enterococcus faecalis commonly colonizes and threatens human
      health. In the present study, we demonstrate the fabrication of a novel
      electrochemical DNA biosensor based on electrodeposited gold nanostructures as a
      transducer substrate combined with toluidine blue (TB) as a redox marker. Binding
      of TB with the single and double stranded DNA (ssDNA and dsDNA) was shortly
      investigated, and based on the results, TB could discriminate between ssDNA and
      dsDNA. A specific thiolated ssDNA sequence was immobilized on the transducer
      substrate, and DNA hybridization was followed by differential pulse voltammetry.
      The DNA biosensor showed excellent performances with high sensitivity and good
      selectivity. The DNA biosensor was applied to detect a synthetic target in a
      linear range of 1.0 * 10-17-1.0 * 10-10 mol L-1 with a limit of detection (LOD)
      of 4.7 * 10-20 mol L-1. In addition, LOD of the DNA biosensor for the detection
      of genomic DNA was found to be 30.1 ng MUL-1.

PMID- 29602080
TI  - Anchoring TGF-beta1 on biomaterial surface via affinitive interactions: Effects
      on spatial structures and bioactivity.
AB  - Protein adsorption on biomaterial surfaces is clinically applied to increase
      therapeutic effects; however, this adsorption is possibly accompanied by
      conformational changes and results in loss of protein bioactivity or adverse
      reactions. In this research, a transforming growth factor beta1 (TGF-beta1)
      affinitive peptide HSNGLPL was grafted onto biopolymer surface to stabilize TGF
      beta1 spatial conformation after adhesion. The peptide with azide end group was
      combined with the propynyl pendant group on polyurethane via copper-catalyzed
      azide-alkyne cycloaddition (CuAAC) click reaction. The final polymer was
      characterized by Fourier transform infrared spectroscopy and proton nuclear
      magnetic resonance spectroscopy, which indicated that the affinitive peptide was
      introduced to the polymer. Quartz crystal microbalance with dissipation (QCM-D)
      was performed to monitor TGF-beta1 adsorption and desorption on the surfaces
      coated with polyurethane with and without peptide combination. Results showed
      that TGF-beta1 adhered on polyurethane surface and formed a compact and rigid
      layer. This layer showed spatial structural change but presented a loose and
      diffuse layer on the peptide-grafted polyurethane surface, indicating stable
      spatial conformation after adherence. Similar regulations were observed on the
      two surfaces where BSA layer was coated in advance. In vivo animal experiments
      revealed that immune reactions and tissue regenerations occurred earlier on
      peptide-modified polyurethane than on polyurethane, which did not undergo peptide
      grafting. This finding confirmed that affinitive interactions may preserve TGF
      beta1 bioactivity on polymer surface after adsorption.

PMID- 29602081
TI  - Juvenile myoclonic epilepsy refractory to treatment in a tertiary referral
      center.
AB  - INTRODUCTION: Juvenile myoclonic epilepsy (JME) is an epileptic syndrome often
      regarded as one in which seizures are relatively easy to control. Individuals
      with JME, however, often require lifelong therapy to remain seizure-free, and a
      few have refractory epilepsy. We ascertained a population with JME and
      characterized a subgroup with refractory epilepsy. MATERIAL AND METHODS: We
      audited and reviewed clinical records of individuals diagnosed with JME
      identified via a sample of 6600 individuals in a clinical database from a
      specialized epilepsy clinic at a tertiary referral center. RESULTS: We identified
      240 people with a diagnosis of JME (146 females), with a mean age at seizure
      onset of 14.2years (SD: 4.5), and a mean age at diagnosis of 15.6years (SD: 4.9).
      Clinical phenotypes seen were classic JME phenotype (88%), childhood absence
      epilepsy evolving into JME (6%), JME with adolescent absences (4%), and JME with
      astatic seizures (2%). More than a quarter (28%) had a family history of
      epilepsy. The most commonly used antiepileptic drug (AED) was sodium valproate in
      78% of individuals, followed by levetiracetam (64%) and lamotrigine (55%). In the
      previous year, 47.5% were seizure-free. Using the International League against
      Epilepsy (ILAE) definitions and considering National Institute for Health and
      Care Excellence (NICE)-recommended AEDs for this syndrome, 121 individuals
      (50.4%) were identified as having refractory epilepsy. DISCUSSION: Juvenile
      myoclonic epilepsy is often regarded as a benign epileptic syndrome, but in this
      setting, half of the individuals with JME have refractory epilepsy with only
      about a quarter of those seizure-free in the previous year. Despite some advances
      in the understanding of this syndrome, there is still much to do before we can
      offer all the best outcomes.

PMID- 29602082
TI  - Emotional reactivity in mesial temporal lobe epilepsy: A pilot study.
AB  - PURPOSE: Emotional reactivity (ER) is the early rapidly evoked response to a
      salient emotional stimulus which influences an individual's coping mechanisms,
      eliciting adaptive responses. We investigated ER in patients with mesial temporal
      lobe epilepsy (MTLE) in order to obtain an emotion-processing measure that can be
      related to behavioral regulation. METHODS: We measured ER in twelve patients with
      (MTLE) using the International Affective Picture System (IAPS), the most widely
      employed instrument to measure ER, and compared their results with those of a
      matched sample of healthy subjects. Ninety color pictures depicting events with
      different kinds of affective valence (pleasant, unpleasant, and neutral) were
      shown to the patients. Unpleasant and pleasant pictures were also distinguished
      depending on whether or not they involved social human conditions. The ER was
      rated on the basis of valence and arousal. RESULTS: Patients with MTLE showed
      higher mean arousal and valence ratings than controls for neutral and socially
      pleasant pictures. A higher valence for unpleasant pictures and a trend toward
      significantly higher arousal and valence for pleasant pictures were also
      recorded. CONCLUSIONS: Patients with MTLE seem to feel the environment in a more
      sensitive and positive way compared with controls, likely in relationship with
      social functioning alterations.

PMID- 29602083
TI  - Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation
      of regulatory data and five criteria for drug selection.
AB  - BACKGROUND: A generalized tonic-clonic seizure (GTCS) is the most severe form of
      common epileptic seizure and carries the greatest risk of harm. The aim of this
      review is to provide an evidence-based guide for the selection of antiepileptic
      drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the
      USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs
      (SGTCSs) and are considered in this paper. METHODS: Each AED is evaluated using
      five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2)
      adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of
      action (MOA). To ensure the inclusions of robust data, only efficacy data
      accepted by regulatory authorities were considered, and data related to adverse
      effects, interactions, adherence, and MOA were all extracted from UK Summaries of
      Product Characteristics (SPCs). RESULTS: (1a) There is class 1 evidence of the
      efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam,
      perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of
      any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta
      analyses supports the use of the four AEDs (levetiracetam, perampanel,
      topiramate, and with less robust data for lamotrigine). (2) AEDs are associated
      with different, but to some extent overlapping, common adverse effect profiles
      but have differing idiosyncratic adverse effects. (3) Pharmacokinetic
      interactions are seen with most, but not all, AEDs and are most common with
      carbamazepine and phenytoin. (4) Good adherence is important for seizure control
      and is influenced by frequency of dosing, among other factors. (5) Mechanism of
      action is also a consideration in rationalising AED selection when switching or
      combining AEDs. CONCLUSION: Ultimately, the choice of AED depends on all these
      factors but particularly on efficacy and adverse effects. Different patients will
      weigh the various factors differently, and the role of the treating physician is
      to provide accurate information to allow patients to make informed choices.

PMID- 29602084
TI  - A comprehensive LC-MS/MS method validation for the quantitative investigation of
      37 fingerprint phytochemicals in Achillea species: A detailed examination of A.
      coarctata and A. monocephala.
AB  - The current study aims to optimize and validate a comprehensive LC-MS/MS method
      for the quantification of 37 phytochemicals (15 phenolic acids, 17 flavonoids, 3
      non-phenolic organic acids, 1 phenolic aldehyde and 1 benzopyrene) in Achillea
      species. Though Achillea species were chosen as real life samples, the current
      method is applicable to a wide range of plant species. The developed method was
      fully validated in terms of linearity, accuracy (recovery), inter-day and intra
      day precision (repeatability), limits of detection and quantification (LOD/LOQ)
      and relative standard uncertainty (U% at 95% confidence level (k = 2)). Reversed
      phase ultrahigh performance liquid chromatography was optimized to achive optimum
      separation for 37 phytochemical compounds and to overcome the suppression
      effects. MS detection was performed using a triple quadrupole mass spectrometer
      and negative or positive ionization modes were optimized for each analyte.
      Multiple reaction monitoring (MRM) was used to quantify the analytes, related
      molecular ions and transition ions were optimized. Phytochemical screening of
      ethanol and methanol-chloroform extracts of root and aerial parts of A. coarctata
      and A. monocephala were performed by using the developed and validated LC-MS/MS
      method. Root and aerial parts of both species have considerable amounts of
      certain phenolic-nonphenolic acids (quinic, malic, fumaric, chlorogenic and
      vanillic acids) and flavonoids (rutin, hesperidin, isoquercitrin, apigetrin,
      luteolin, apigenin). Additionally, total phenolic and flavonoid amounts,
      antioxidant (DPPH free radical scavenging assay, ABTS radical cation
      decolorization assay, beta-carotene lipid peroxidation test system and CUPRAC
      cupper reduction capacity methods), anticholinesterase, tyrosinase, urease
      inhibition and cytotoxic activities (on HeLa (Human Cervical Carcinoma Cell Line)
      of A. coarctata and A. monocephala were also investigated. It has been determined
      that the studied Achillea species, that are rich in total phenolic-flavonoid and
      chlorogenic acid contents, have high antioxidant and cytotoxic potential at the
      same time. According to the results of LC-MS/MS, antioxidant and cytotoxic
      activity studies, after detailed chemical investigation and toxicity studies on
      these species, A. coarctata and A. monocephala may be promoted as promising
      sources of natural agents and used for the development of nutraceuticals or
      functional food ingredients in future.

PMID- 29602085
TI  - Towards the identification of alkaline phosphatase binding ligands in Li-Dan-Hua
      Shi pills: A Box-Behnken design optimized affinity selection approach tandem with
      UHPLC-Q-TOF/MS analysis.
AB  - Alkaline phosphatase conjugated magnetic microspheres were synthesized via amide
      reaction, and employed as an effective adsorbent in affinity selection of binding
      ligands followed by UHPLC-Q-TOF/MS analysis. The analytical validity of the
      developed approach was evaluated under optimized conditions and the following
      figures of merit were obtained: linearity, 0.01-0.5 g L-1 with good determination
      coefficients (R2 = 0.9992); limits of detection (LODs), 0.003 g L-1; and limits
      of quantitation (LOQ), 0.01 g L-1. The precision (RSD%) of the proposed affinity
      selection approach was studied based on intra-day (0.8%) and inter-day (1.3%)
      precisions. Finally, the adsorbent was successfully applied to identification of
      binding ligands in Li-Dan-Hua-Shi pills and good recoveries were obtained in the
      range from 96.9 to 99.4% (RSDs 1.6-3.0%).

PMID- 29602086
TI  - Implementation options for DNA-based identification into ecological status
      assessment under the European Water Framework Directive.
AB  - Assessment of ecological status for the European Water Framework Directive (WFD)
      is based on "Biological Quality Elements" (BQEs), namely phytoplankton, benthic
      flora, benthic invertebrates and fish. Morphological identification of these
      organisms is a time-consuming and expensive procedure. Here, we assess the
      options for complementing and, perhaps, replacing morphological identification
      with procedures using eDNA, metabarcoding or similar approaches. We rate the
      applicability of DNA-based identification for the individual BQEs and water
      categories (rivers, lakes, transitional and coastal waters) against eleven
      criteria, summarised under the headlines representativeness (for example
      suitability of current sampling methods for DNA-based identification, errors from
      DNA-based species detection), sensitivity (for example capability to detect
      sensitive taxa, unassigned reads), precision of DNA-based identification
      (knowledge about uncertainty), comparability with conventional approaches (for
      example sensitivity of metrics to differences in DNA-based identification), cost
      effectiveness and environmental impact. Overall, suitability of DNA-based
      identification is particularly high for fish, as eDNA is a well-suited sampling
      approach which can replace expensive and potentially harmful methods such as gill
      netting, trawling or electrofishing. Furthermore, there are attempts to replace
      absolute by relative abundance in metric calculations. For invertebrates and
      phytobenthos, the main challenges include the modification of indices and
      completing barcode libraries. For phytoplankton, the barcode libraries are even
      more problematic, due to the high taxonomic diversity in plankton samples. If
      current assessment concepts are kept, DNA-based identification is least
      appropriate for macrophytes (rivers, lakes) and angiosperms/macroalgae
      (transitional and coastal waters), which are surveyed rather than sampled. We
      discuss general implications of implementing DNA-based identification into
      standard ecological assessment, in particular considering any adaptations to the
      WFD that may be required to facilitate the transition to molecular data.

PMID- 29602087
TI  - Development of a protocol for environmental impact studies using causal
      modelling.
AB  - 1- A major challenge when assessing the impacts of human activities on the
      globe's natural resources is to account for the impacts of land use versus
      natural spatiotemporal variation in system dynamics. Current freshwater
      assessments are unable to resolve spatiotemporal confounding through study
      designs or statistical analyses. Observational studies typically fail to consider
      the period-by-location interaction in the absence of an impact. 2- Here, I
      address the problem of spatiotemporal confounding using causal modelling based on
      spatiotemporal data to infer causal effects of wastewater on biotic ecosystems. A
      combination of statistical analysis and causation theory was used to address
      confounding bias. Benthic macroinvertebrate and environmental variable data were
      collected from locations upstream and downstream of a wastewater treatment plant
      discharge point in south-eastern Australia over 1.5 years. The composite
      hypotheses based on the theoretical relationships among these variables were
      summarised in a causal diagram. Model building and testing was conducted using
      Structural Equation Modelling (SEM). Distance-based redundancy analysis (dbRDA)
      was used for model building and hypothesis testing. 3- The results indicated that
      the causal effects of effluent on macroinvertebrate communities could be inferred
      using causal modelling. The macroinvertebrate communities responded to water
      quality degradation with a clear shift in community composition after the
      discharge point and this change varied seasonally. Chlorophyll a, total organic
      carbon, zinc, conductivity, temperature, and its interaction with conductivity,
      were important determinants of the macroinvertebrate community composition.
      Causal models also explained the spatiotemporal variations in environmental
      variables. The consistency of data with the structure of the causal diagram was
      confirmed with global Fisher's C-test. 4- Causal modelling has been shown to be a
      useful tool in environmental impact studies. In this study, the usefulness of
      causal modelling was attributed to its proficiency in combining all of the
      elements necessary for an efficient risk assessment through dealing with spatial
      and temporal confounding, facilitating communication between scientists and
      resource managers, and supporting management decision making.

PMID- 29602088
TI  - Interactions of natural organic matter on the surface of PVP-capped silver
      nanoparticle under different aqueous environment.
AB  - It is now widely accepted that coating on the nano-surface would critically
      dictate the uptake and cytotoxicity of engineering nanomaterials. However, the
      influence of natural organic matter (NOM) on the surface is quite limited to
      humic substances, while the diversity of NOM is neglected. In the present study,
      we tried to investigate the change of surface in the coexistence of bovine serum
      albumin (BSA) and humic acid (HA). The isothermal titration calorimetric
      measurements show that HA can combine with BSA in both freshwater or seawater,
      however, the patterns are different. In freshwater, HA lowered the adsorption of
      BSA on PVP-capped AgNPs through complexation with BSA, which prevented the
      contact of sulfur in BSA with PVP-AgNPs. Then in seawater, BSA retained its
      sulfur availability to bind with PVP-AgNPs. Furthermore, the toxicity of PVP
      AgNPs incubated in the BSA/HA solution was evaluated by measuring the level of
      reactive oxygen species generated by Escherichia coli. The results indicated
      that, in seawater, the adsorbed BSA promoted the toxicity of PVP-AgNPs in the
      presence of Ca2+ and Mg2+, but the presence of HA limited this effect.

PMID- 29602089
TI  - Women's asset ownership and children's nutritional status: Evidence from Papua
      New Guinea.
AB  - This study examines how women's asset ownership is associated with children's
      nutritional status in Papua New Guinea, a country with some of the most severe
      child malnutrition in the world. The 2009-2010 Household Income and Expenditure
      Survey is employed, but restricted to children under the age of 72 months living
      with married mothers, leaving a final analytic sample of 1651. Asset ownership is
      expected to strengthen mothers' income-generating capacity and their bargaining
      power within the home, which increases investments in children's health. Women's
      ownership of fishing and agricultural equipment (important for meeting
      subsistence needs and for generating cash earnings) appears to be driving most of
      the results. OLS regression results point to beneficial effects of maternal asset
      ownership for children's height-for-age, weight-for-height, and weight-for-age Z
      scores, and results from detailed quantile regressions indicate that these
      effects occur at various parts of the distribution, especially for children's WAZ
      scores.

PMID- 29602090
TI  - Male-female differences in households' resource allocation and decision to seek
      healthcare in south-eastern Nigeria: Results from a mixed methods study.
AB  - Ability to influence household decision-making has been shown to increase with
      improved social capital and power and is linked to better access to household
      financial resources and other services outside the household including
      healthcare. To examine the male-female differences in household custody of
      financial resources, decision-making, and type of healthcare utilised, we used a
      mixed methods approach of cross-sectional household surveys and focus-group
      discussions (FGDs). Data was collected between 10 January-28 February 2011. We
      analyzed a sample of 411 households and a sub-sample of 223 households with a
      currently married head. We conducted six single-sex FGDs in 3 communities (1
      urban, 2 rural) among a random sub-sample of participants in the survey. We
      performed univariate, bivariate, and logistic regression analyses with a 95%
      confidence interval. For the qualitative data, we performed thematic analysis
      where broad themes relevant to the research objective were abstracted. In all
      households and in those with a married head, sick male members were less likely
      to forgo healthcare (aORall0.87, 95% CI 0.80-0.90; aORmarried0.52, 95% CI 0.18
      0.83) and more likely to utilise formal healthcare relative to female sick
      members (aORall3.36, 95% CI 3.20-3.87; aORmarried19.50, 95% CI 9.62-39.52).
      Formal healthcare providers are medically trained while informal providers are
      untrained vendors that dispense medications for profit. There were more reports
      of sole custody of household resources among men within households with married
      heads. Joint decision-making on healthcare expenditure improved women's access to
      healthcare but is not reflective of unhindered access to household financial
      resources. Qualitatively, women spoke of seeking permission from male household
      head before expenditure was incurred, while male heads spoke of concealing
      household financial resources from their spouse. Gender constructs and male
      female differences have important effects on household resource allocation and
      healthcare utilisation.

PMID- 29602092
TI  - Removal of priority and emerging pollutants from aqueous media by adsorption onto
      synthetic organo-funtionalized high-charge swelling micas.
AB  - In this work, the removal of different types of emerging pollutants (four
      perfluoroalkyl compounds, two preservatives, three surfactants and nine
      pharmaceutical compounds) from aqueous solution by adsorption onto two novel
      synthetic clays, a high-charge swelling mica (Na-Mica-4) and an organo
      functionalized mica (C18-Mica-4), was evaluated. Na-Mica-4 and C18-Mica- 4 were
      prepared and characterized by X-Ray diffraction, Zeta potential, specific surface
      area, thermogravimetric analysis and transmission electron microscopy, before and
      after adsorption experiments. The influence of the aqueous sample pH, salt
      addition and extraction time in the removal were evaluated. The results showed
      the high adsorption affinity of C18-Mica-4 for most of the emerging pollutants
      analysed after a removal time of 24 h (14 out of 18 pollutants were effectively
      removed [70-100%]). A high correlation was observed between the log Kow of the
      selected emerging pollutants and the adsorption onto C18-Mica-4. The results also
      indicate that adsorption occurs in the interlayer space. While the removal rates
      with Na-Mica-4 were in the range 8-97% after seven days, some of the compounds,
      perfluorobutanoic acid and most of pharmaceutically active compounds, were not
      adsorbed onto the high-charge mica. C18-Mica- 4 was effectively used for the
      removal of contaminants from four types of water samples.

PMID- 29602091
TI  - Developing religiously-tailored health messages for behavioral change:
      Introducing the reframe, reprioritize, and reform ("3R") model.
AB  - RATIONALE: As community health interventions advance from being faith-placed to
      authentically faith-based, greater discussion is needed about the theory,
      practice, and ethics of delivering health messages embedded within a religious
      worldview. While there is much potential to leverage religion to promote health
      behaviors and improve health outcomes, there is also a risk of co-opting
      religious teachings for strictly biomedical ends. OBJECTIVE: To describe the
      development, implementation, and ethical dimensions of a conceptual model for
      religiously-tailoring health messages. METHOD: We used data from 6 focus groups
      and 19 interviews with women aged 40 and older sampled from diverse Muslim
      community organizations to map out how religious beliefs and values impact
      mammography-related behavioral, normative and control beliefs. These beliefs were
      further grouped into those that enhance mammography intention (facilitators) and
      those that impede intention (barriers). In concert with a multi-disciplinary
      advisory board, and by drawing upon leading theories of health behavior change,
      we developed the "3R" model for crafting religiously-tailored health messages.
      RESULTS: The 3R model addresses barrier beliefs, which are beliefs that
      negatively impact adopting a health behavior, by (i) reframing the belief within
      a relevant religious worldview, (ii) reprioritizing the belief by introducing
      another religious belief that has greater resonance with participants, and (iii)
      reforming the belief by uncovering logical flaws and/or theological
      misinterpretations. These approaches were used to create messages for a peer-led,
      mosque-based, educational intervention designed to improve mammography intention
      among Muslim women. CONCLUSIONS: There are benefits and potential ethical
      challenges to using religiously tailored messages to promote health behaviors.
      Our theoretically driven 3R model aids interventionists in crafting messages that
      address beliefs that hinder healthy behaviors. It is particularly useful in the
      context of faith-based interventions for it highlights the ethical choices that
      must be made when incorporating religious values and beliefs in tailored
      messages.

PMID- 29602093
TI  - Fate of leaf litter deposits and impacts on oxygen availability in bank
      filtration column studies.
AB  - Degradation of particulate organic carbon (POC) such as leaf litter might deplete
      dissolved oxygen within the upper layers of bank filtration, an efficient and
      robust barrier for pathogens and for various organic micro-pollutants (OMP) in
      water supply systems worldwide. The degradation of OMP during bank filtration
      depends on the redox conditions. The present study aimed at identifying the
      impacts and fates of different local leaves on the oxygen consumption and the
      possible biological degradation of indicator OMP. Oxygen concentrations initially
      decreased within the columns from around 8 mg/L in the influent to low
      concentrations indicating extensive consumption within a short travel distance.
      Still a substantial oxygen consumption was observed after 250 days. OMP
      concentrations were not significantly affected by the microbial processes. A
      layer of calcium carbonate crystallites was observed on the POC layer. Some leaf
      fragments appeared to be persistant towards degradation and the carbon content
      relative to nitrogen and sulfur contents decreased within 250 days. The results
      demonstrate that trees at bank filtration sites might have a strong long-term
      impact on the subsurface redox conditions.

PMID- 29602094
TI  - Dose-response relationship between blood lead levels and hematological parameters
      in children from central China.
AB  - BACKGROUND: Lead is a heavy metal that can affect the human hematological system.
      However, reports are limited on the dose-response relationship between blood lead
      levels (BLLs) and hematological parameters in children. This study aimed to
      explore the dose-response relationship between BLLs and hematological
      measurements among children in China. METHODS: A cross-sectional design was used.
      A total of 743 children aged 5-8 years were recruited from two counties in
      central China. The BLLs and blood levels of iron, zinc, and calcium were
      determined, and hematological parameters were measured. RESULTS: All
      hematological measurements and BLLs were logarithm-transformed to ensure a normal
      distribution. The geometric mean of the BLLs of all children was 82.4 MUg/L.
      Forty-one percent of the children had BLLs >= 100 MUg/L. The lead-poisoning
      percentages of the children were significantly associated with gender, age,
      district of residence, and environmental lead exposure level. Multivariate linear
      regression analyses showed no significant linear correlation between BLL and each
      hematological parameter among the children with BLLs >= 100 MUg/L. The analyses
      also revealed a small increase in red blood cell count (RBC) with increasing BLLs
      in the BLLs < 100 MUg/L group (beta = 0.03, P =  0.048). A negative association
      was noted between BLLs and blood platelet (PLT) count in the children with BLLs <
      100 MUg/L (beta = -0.90, P < 0.001). Logistic regression analyses showed that
      BLLs were significantly associated with decreased hemoglobin (Hb) levels, RBC
      counts, PLT counts and mean corpuscular hemoglobin (MCH) after adjusting for
      potential confounders. Such analyses also revealed a dose-response relationship
      between the BLLs and hematological parameters (Hb level, RBC count, and PLT
      count). The children with BLLs >= 100 MUg/L were 2.72, 2.51, and 3.76 times more
      likely to achieve decreased RBC counts, Hb levels and PLT counts, respectively,
      compared to those with BLLs < 100 MUg/L. Compared with children with BLLs < 100
      MUg/L, those with BLLs >= 100 MUg/L were 3.16 and 4.38 times more likely to show
      decreased Hb levels and PLT counts respectively in the high-level lead-exposure
      group and 4.33 times more likely to achieve a decreased PLT count in the low
      level lead-exposure group. The individuals with BLLs of the highest quartile were
      3.65, 5.87, and 29.23 times more likely to exhibit decreased Hb levels, RBC
      counts, and PLT counts, respectively, than the children with BLLs of the lowest
      quartile. CONCLUSION: Our findings suggested a negative association between BLLs
      and hematological indicators (Hb level, RBC count, PLT count and MCH). A strong
      negative, non-linear dose-response relationship was also showed between BLLs and
      hematological parameters (Hb level, RBC count, and PLT count).

PMID- 29602095
TI  - Viral load and antibody boosting following herpes zoster diagnosis.
AB  - BACKGROUND: Acute varicella zoster virus (VZV) replication in shingles is
      accompanied by VZV antibody boosting. It is unclear whether persisting virus
      shedding affects antibody levels. OBJECTIVES: To investigate the relationship
      between VZV viral load and antibody titres in shingles patients during six months
      following diagnosis and assess whether VZV antibody titre could discriminate
      patients with recent shingles from healthy population controls. STUDY DESIGN: A
      prospective study of 63 patients with active zoster. Blood samples were collected
      at baseline, one, three and six months to measure VZV DNA and IgG antibody titre.
      We compared VZV antibody titres of zoster patients and 441 controls. RESULTS: In
      acute zoster, viral load was highest at baseline and declined gradually over the
      following six months. Mean antibody titres rose fourfold, peaking at one month
      and remaining above baseline levels throughout the study. Antibody levels at one,
      three and six months after zoster were moderately correlated with baseline but
      not subsequent viral load. Regarding use of antibody titres to identify recent
      shingles, to achieve 80% sensitivity, specificity would be 23.4%, 67.7%, 64.8%
      and 52.6%, at baseline, visit 2, 3 and 4 respectively, whilst to achieve 80%
      specificity, sensitivity would be 28.3%, 66.1%, 52.6%, 38.6%, at baseline, visit
      2, 3 and 4 respectively. CONCLUSIONS: Clinical VZV reactivation boosted VZV
      antibody levels and the level of boosting was dependent upon baseline viral
      replication. While antibody titres could discriminate patients with shingles 1-6
      months earlier from blood donor controls, there was a large trade-off between
      sensitivity and specificity.

PMID- 29602096
TI  - Clinical burden of hepatitis E virus infection in a tertiary care center in
      Flanders, Belgium.
AB  - BACKGROUND: Hepatitis E virus (HEV) infection is increasingly recognized as a
      cause of hepatitis in developed countries. A high HEV IgG seroprevalence in
      humans and pigs is reported as well as sporadic clinical cases of autochtonous
      HEV but there are currently no data available on the clinical burden of HEV in
      Belgium. OBJECTIVES: The objective of the current study was to evaluate the
      actual clinical burden of HEV infections in our tertiary care center in Flanders,
      Belgium. STUDY DESIGN: In the setting of Ghent University Hospital, patients were
      assessed for the presence of HEV IgG and IgM as well as HEV RNA if no other cause
      was found for one of the following clinical presentations: a) elevation of liver
      enzymes in post-liver transplant; b) suspicion of acute or toxic hepatitis; c)
      unexplainable elevation of liver enzymes; d) cirrhosis with acute-on-chronic
      exacerbation. RESULTS: In a period of 39 months (January 2011-April 2014) 71
      patients were enrolled. HEV IgG was found positive in 13 (18,3%) patients; HEV
      IgM in 6 patients (8,5%) and HEV RNA in 4 (5,6%) patients. All HEV IgM/RNA
      positive patients were male, aged 41-63, and classified in the clinical groups
      a), b) or d). HEV IgG seroprevalence was slightly higher but not significantly
      different from the seroprevalence in the general population in this region in
      Belgium previously reported to be 14% (p-value 0.41) by our group. CONCLUSIONS:
      HEV should be considered as a cause of liver pathology especially in middle-aged
      men with elevation of liver enzymes.

PMID- 29602097
TI  - Chemical reactivity of natural peat towards U and Ra.
AB  - Peat is a complex material with several organic constituents that contribute to
      its high capacity to retain metals. In the context of uranium mining, peat can
      accumulate high concentrations of uranium and its decay products such as radium.
      Hence, interaction with peat appears to be a key factor in the understanding of
      the geochemical mechanisms controlling the fate of these products. This study
      aims to determine the sorption properties of two trace elements, U(VI) and 226Ra,
      on natural organic matter from peat. The presented method was applied to both
      natural peat samples originating from a mining context, with various contents of
      organic matter (from 40 to 70%) and detrital loads, and wetland peat with a more
      than 98% composition of organic matter. In the present study, considering peat
      material as a sorbent, its reactivity towards metals and other contaminants can
      be described as that of an ion-exchanger. A relatively simple model of ion
      exchange based on the sorption properties of carboxylic sites has been applied
      with success to describe the sorption of uranium and radium. In the general
      overview of the different mechanisms able to control the mobility of these
      radionuclides in a uranium mining context, organic matter is likely one of the
      main contributors to radionuclide scavenging even under oxic conditions.

PMID- 29602098
TI  - Degradation of tetracycline in a schorl/H2O2 system: Proposed mechanism and
      intermediates.
AB  - Schorl could perform as an extremely promising catalyst for decomposing
      tetracycline hydrochloride (TC) due to its high degradation efficiency, low cost,
      chemical stability, easy recovery and repeatable utilization. Comparisons of TC
      degradation indifferent systems showed that schorl/H2O2 system exhibited the
      optimum pollutant elimination and TOC removal efficiencies. Kinetics and possible
      mechanisms of TC degradation were clarified. The OH generated on the schorl
      surface and O2-/HO2 were the main reactive species responsible for TC oxidation.
      Six possible intermediates were identified, and possible transform mechanisms and
      pathways were explored. Active radicals were inclined to attack the CC double
      bond, dimethylamino and phenolic moieties of TC molecular. The principal
      intermediate products were generated through N-demethylation, oxidation and
      rearrangement.

PMID- 29602099
TI  - Synthesis of cerium and nickel doped titanium nanofibers for hydrolysis of sodium
      borohydride.
AB  - A recyclable titanium nanofibers, doped with cerium and nickel doped was
      successfully synthesized by using sol-gel and electrospinning method for hydrogen
      generation from alkali free hydrolysis of NaBH4. The resultant nanocomposite was
      characterized to find out the structural and physical-chemical properties by a
      series of analytical techniques such as FT-IR (Fourier transform infrared
      spectroscopy), XRD (X-ray diffraction), SEM (scanning electron microscope), EDX
      (energy-dispersive X-ray spectroscopy),N2 adsorption-desorption and BET (Brunauer
      Emmett-Teller), etc. The results revealed that cerium and nickel nanoparticles
      were homogeneously distributed on the surface of the TiO2 nanofibers due to
      having similar oxidation state and atomic radium of TiO2nanofibers with CeO2 and
      NiO for the effective immobilization of metal ions. The NiO doped catalyst showed
      superior catalytic performance towards the hydrolysis reaction of NaBH4 at room
      temperature. These catalysts have ability to produce 305 mL of H2 within the time
      of 160 min at room temperature. Additionally, reusability test revealed that the
      catalyst is active even after five runs of hydrolytic reaction, implying the as
      prepared NiO doped TiO2 nanofibers could be considered as a potential candidate
      catalyst for portable hydrogen fuel system such as PEMFC (proton exchange
      membrane fuel cells).

PMID- 29602100
TI  - Characterization of diurnal variations of PM2.5 acidity using an open
      thermodynamic system: A case study of Guangzhou, China.
AB  - Aerosol acidity has significant implications for atmospheric processing, and high
      time-resolution measurements can provide critical insights into those processes.
      This paper reports diurnal variations of aerosol acidity characterized using an
      open thermodynamic system in Guangzhou, China. Hourly measurements of PM2.5
      associated ionic species and related parameters were carried out during June
      September 2013 followed by application of the Extended Aerosol Inorganic Model in
      open mode to estimate aerosol pH. The model-estimated aerosol pH was 2.4 +/- 0.3,
      and the pH diurnal profile exhibited peaks in the early morning (6 a.m.) and
      troughs in the afternoon (2 p.m.) that appeared to be constrained by liquid water
      content (LWC) and free H+. A linear regression model was developed to predict
      aerosol pH, which performed strongly with 4 variables during daytime (NH4+, Na+,
      SO42- and RH; R2 = 0.95) and 3 during nighttime (NH4+, SO42- and RH; R2 = 0.91).
      The effect of aerosol acidity on the partitioning of HNO3, HCl and NH3 was
      studied based on theoretical considerations and measurement data. The fractions
      in particulate phase for acidic compounds correlated strongly with pH (R2 = 0.64
      0.69) while that for NH3, interestingly, was weak (R2 = 0.17). Analytical
      expressions were developed to explain these observations and it was concluded
      that the partitioning of HCl and HNO3 was more sensitive to pH compared to that
      of NH3. These results are significant in terms of potential atmospheric depletion
      rates of HCl and HNO3 in the region and stress the need for future studies in
      this direction.

PMID- 29602101
TI  - From biowaste to magnet-responsive materials for water remediation from
      polycyclic aromatic hydrocarbons.
AB  - Composted urban biowaste-derived substances (BBS-GC) are used as carbon sources
      for the preparation of carbon-coated magnet-sensitive nanoparticles obtained via
      co-precipitation method and the subsequent thermal treatment at 550  degrees C
      under nitrogen atmosphere. A multitechnique approach has been applied to
      investigate the morphology, magnetic properties, phase composition, thermal
      stability of the obtained magnet-sensitive materials. In particular, pyrolysis
      induced modifications affecting the BBS-GC/carbon shell were highlighted. The
      adsorption capacity of such bio-derivative magnetic materials for the removal of
      hydrophobic contaminants such as polycyclic aromatic hydrocarbons was evaluated
      in order to verify their potential application in wastewater remediation process.
      The promising results suggest their use as a new generation of magnet-responsive
      easily-recoverable adsorbents for water purification treatments.

PMID- 29602102
TI  - Immobilization of ligninolytic enzymes from white-rot fungi in cross-linked
      aggregates.
AB  - Ligninolytic enzymes from white-rot fungi are widely used in biotechnological
      processes. However, the application of these enzymes as free enzymes is limited
      due to their instability and lack of reusability. Enzyme stabilization is
      therefore a major challenge in biocatalytic process research, and immobilization
      methods are desirable. Using cross-linked enzyme aggregates (CLEAs) such as
      magnetic CLEAs, porous-CLEAs and combi-CLEAs is a promising technique for
      overcoming these issues. Cross-linking methods can stabilize and immobilize
      enzymes by interconnecting enzyme molecules via multiple bonds using cross
      linking agents such as glutaraldehyde. The high catalyst density and microporous
      assembly of CLEAs guarantee high catalyst activity, which, together with their
      long shelf life, operational stability, and reusability, provide a cost-efficient
      alternative to matrix-assisted immobilization approaches. Here, we review current
      progress in ligninolytic enzyme immobilization and provide a comprehensive review
      of CLEAs. Moreover, we summarize the use of these CLEAs for biocatalysis
      processes, bioremediation such as dye decolourization, wastewater treatment or
      pharmaceutically active compound elimination.

PMID- 29602103
TI  - Investigation of the performance behavior of a forward osmosis membrane system
      using various feed spacer materials fabricated by 3D printing technique.
AB  - Recently, feed spacer research for improving the performance of a membrane module
      has adopted three-dimensional (3D) printing technology. This study aims to
      improve the performance of membrane feed spacers by using various materials and
      incorporating 3D printing. The samples were fabricated after modeling with 3D
      computer-aided design (CAD) software to investigate the mechanical strength,
      water flux, reverse solute flux, and fouling performances. This research was
      performed using acrylonitrile butadiene styrene (ABS), polypropylene (PP), and
      natural polylactic acid (PLA) as printing material, and the spacer model was
      produced using a diamond-shaped feed spacer, with a commercially available
      product as a reference. The 3D printed samples were initially compared in terms
      of size and precision with the 3D CAD model, and deviations were observed between
      the products and the CAD model. Then, the spacers were tested in terms of
      mechanical strength, water flux, reverse solute flux, and fouling (alginate-based
      waste water was used as a model foulant). Although there was not much difference
      among the samples regarding the water flux, better performances than the
      commercial product were obtained for reverse solute flux and fouling resistance.
      When comparing the prominent performance of natural PLA with the commercial
      product, PLA was found to have approximately 10% less fouling (based on foulant
      volume per unit area and root mean square roughness values), although it showed
      similar water flux. Thus, another approach has been introduced for using bio
      degradable materials for membrane spacers.

PMID- 29602104
TI  - Geographical variations of cadmium and arsenic concentrations and arsenic
      speciation in Chinese rice.
AB  - Rapid industrialization in China in recent decades has resulted in soil
      contamination in some areas, raising the concern about food safety. Consumption
      of rice represents a major exposure route for the toxic elements cadmium (Cd) and
      arsenic (As). We collected 160 polished rice from local markets in 20 provinces
      in China and determined total Cd and As concentrations and As speciation. Total
      Cd concentration ranged from below the detection limit to 0.77 mg kg-1, with 10%
      of the samples exceeding the Chinese limit (0.2 mg kg-1). Rice Cd concentration
      showed a distinct geographical pattern, increasing from low levels in the north
      to high levels in the south of China. Median daily Cd intake from rice varied
      from 0.01 MUg kg-1 body weight in the north to 0.61 MUg kg-1 body weight in the
      south of China, representing between 1% and 73% of the tolerable daily intake
      (TDI) recommended by FAO/WHO. The highest median Cd intake from rice was in Hunan
      province with 2 times TDI. Total As concentration ranged from 0.011 to 0.186 mg
      kg-1, with inorganic As (iAs) and dimethylarsinic acid (DMAs) on average
      accounting for 69% and 31%, respectively. All samples were below the Chinese
      limit for iAs in rice (0.2 mg kg-1). There was no clear geographical pattern in
      rice total As concentration, but rice produced in northeastern China contained
      higher percentages of DMAs and lower percentages of iAs. This study highlights a
      high risk of Cd exposure from rice consumption for the population of southern
      China and suggested strategies for reducing Cd accumulation in rice crop.

PMID- 29602105
TI  - Application of a rotating impeller anode in a bioelectrochemical anaerobic
      digestion reactor for methane production from high-strength food waste.
AB  - In this study, a practical bioelectrochemical anaerobic digestion (BEAD) reactor
      equipped with a rotating STS304 impeller was tested to verify its methane
      production performance. Methane production in the BEAD reactor was possible
      without accumulation of volatile fatty acids (VFAs) and decreases in pH at high
      organic loading rates (OLRs) up to 6 kg-COD/m3.d (COD: chemical oxygen demand).
      Methane production in a BEAD-O (open circuit) reactor was inhibited at OLRs above
      4 kg-COD/m3.d; however, the performance could be recovered bioelectrochemically
      by supplying voltage. The population density of hydrogenotrophic methanogens
      increased to 73.3% in the BEAD-C (closed circuit) reactor, even at high OLRs,
      through the removal of VFAs and conversion of hydrogen to methane. The energy
      efficiency in the BEAD-C reactor was 85.6%, indicating that the commercialization
      of BEAD reactors equipped with rotating STS304 impeller electrodes is possible.

PMID- 29602106
TI  - Enrichment of sulfate reducing anaerobic methane oxidizing community dominated by
      ANME-1 from Ginsburg Mud Volcano (Gulf of Cadiz) sediment in a biotrickling
      filter.
AB  - This study was performed to enrich anaerobic methane-oxidizing archaea (ANME)
      present in sediment from the Ginsburg Mud Volcano (Gulf of Cadiz) in a
      polyurethane foam packed biotrickling filter (BTF). The BTF was operated at 20
      (+/-2)  degrees C, ambient pressure with continuous supply of methane for 248
      days. Sulfate reduction with simultaneous sulfide production (accumulating ~7 mM)
      after 200 days of BTF operation evidenced anaerobic oxidation of methane (AOM)
      coupled to sulfate reduction. High-throughput sequence analysis of 16S rRNA genes
      showed that after 248 days of BTF operation, the ANME clades enriched to more
      than 50% of the archaeal sequences, including ANME-1b (40.3%) and ANME-2 (10.0%).
      Enrichment of the AOM community was beneficial to Desulfobacteraceae, which
      increased from 0.2% to 1.8%. Both the inoculum and the BTF enrichment contained
      large populations of anaerobic sulfur oxidizing bacteria, suggesting extensive
      sulfur cycling in the BTF.

PMID- 29602107
TI  - Efficient elimination of sulfonamides by an anaerobic/anoxic/oxic-membrane
      bioreactor process: Performance and influence of redox condition.
AB  - Membrane bioreactors (MBRs) were shown contradictory results for the removal of
      antibiotics, such as sulfonamides (SAs), from wastewater in different studies,
      which highlighted the necessity for comprehensive investigation on removal
      mechanisms of sulfonamides in well-controlled lab-scale MBRs. In the present
      study, the removal performance of nine SAs by a lab-scale anaerobic/anoxic/oxic
      membrane bioreactor (A1/A2/O-MBR) was studied at environmental relevant
      concentrations. The results showed that all the SAs were efficiently eliminated
      (93.9%-97.5%) in the A1/A2/O-MBR, much more efficiently than the previously
      reported MBR-based processes. The largest contribution to the total removal was
      made by the aerobic reactor (71.1%-85.3%) A small portion of SAs (7.1%-22.5%)
      were removed by anoxic reactor. Activated sludge in the A1/A2/O-MBR was harvested
      to conduct batch experiments to further study the removal and degradation
      kinetics of SAs under anaerobic, anoxic and aerobic conditions. The results
      indicated that only sulfisoxazole could be removed under anaerobic condition.
      Modest biodegradation of individual SAs (15-33%) was observed under anoxic
      condition. Under aerobic condition, most investigated SAs underwent an efficient
      and fast removal (68-77%) in 6h without a lag phase; while sulfisomidine and
      sulfamethazine were removed less efficiently (approximately 47% after 6h
      reaction). The aerobic and anoxic degradation of SAs fitted the first-order
      kinetics model well, and the obtained biodegradation rate constants (k1) were
      reliable to predict removal efficiencies of SAs in the anoxic and aerobic reactor
      of A1/A2/O-MBR based on their HRTs.

PMID- 29602108
TI  - Filling the missing data gaps of daily MODIS AOD using spatiotemporal
      interpolation.
AB  - Aerosol is an important component of the atmosphere that affects the environment,
      climate, and human health. Remote sensing is an efficient observation method for
      monitoring global aerosol distribution and changes over time. The daily Moderate
      Resolution Imaging Spectroradiometer (MODIS) level-2 aerosol optical depth (AOD)
      (Collection 6) product (10 km resolution) is often used to study climate change
      and air pollution. However, the product is prone to yielding large amounts of
      data gaps due to the unfeasibility of retrieving reliable estimates under cloudy
      conditions, and these data gaps inevitably affect the results and analysis of the
      product's application. In this study, a geostatistical data interpolation
      framework based on the spatiotemporal kriging method was implemented to
      interpolate satellite AOD products in Beijing, China. Compared to the ordinary
      kriging method for filling data gaps, the spatiotemporal interpolation not only
      utilizes spatial autocorrelation but also considers the temporal and
      spatiotemporal autocorrelations between different locations. In the study region,
      the completeness of the spatiotemporal-interpolated AOD product reaches 67.73%,
      which is significantly superior to the completeness of the original MODIS product
      (14.27%) and that of the spatial kriging-interpolated AOD product (33.3%). The
      cross-validation results show that the mean absolute error of the spatiotemporal
      kriging results (0.07) is lower than that of the ordinary kriging (0.09).

PMID- 29602109
TI  - Multiple approaches to assess human health risks from carcinogenic and non
      carcinogenic metals via consumption of five fish species from a large reservoir
      in Turkey.

PMID- 29602110
TI  - Degradation and dispersion limit environmental DNA detection of rare amphibians
      in wetlands: Increasing efficacy of sampling designs.
AB  - The detection of rare macroorganisms using environmental DNA (eDNA) is a powerful
      new method for conservation and management; the efficacy of this method is
      affected by physiological, ecological, and hydrological processes. Understanding
      the processes limiting eDNA detection and accounting for those factors with
      optimized sampling designs is critical for realizing the potential of this tool.
      Amphibians are a focus of conservation programs globally and are often difficult
      to detect, presenting a challenge for effective action. To increase the ability
      of eDNA techniques to inform conservation and management programs, we
      investigated the eDNA detection of amphibians compared with field surveys for six
      species across a gradient of environmental factors expected to affect eDNA
      detection in three different systems: perennial wetlands, intermittent wetlands,
      and acidic intermittent wetlands. We applied a baseline sampling design in each
      wetland and used an occupancy modeling approach to evaluate evidence for
      processes limiting detection for each species given the presence of the target
      species. Evidence weights indicated that limiting processes varied across systems
      and included those associated with increased degradation (pH<5, temperature>25
      degrees C) and limited dispersion (wetland area>1200m2, sample volume<200mL).
      Optimized sampling protocols based on model results included an increased number
      of sampling locations in large and highly degradative (acidic) wetlands and
      increased filter pore size in high-particulate systems. These improved designs
      compensated for the previously limiting factors and yielded average detection
      rates of 0.62-0.86 per water sample. Degradation and dispersion processes appear
      to strongly influence the detection of amphibians in wetlands. Optimized,
      adaptive sampling designs can greatly increase the efficacy of eDNA monitoring
      approaches.

PMID- 29602111
TI  - Formulation approaches to reduce post-application pesticide volatilisation from
      glass surfaces.
AB  - Volatilisation is one of the main pathways for pesticide emission to the
      atmosphere. While formulation strategies and adjuvants are known to affect the
      fate of active ingredient, no general volatilisation reducing guidelines exist
      for formulation purposes. Moreover, as limited information on formulation effects
      is available, current pesticide fate models lack parameters characterising
      reduction of active ingredient volatilisation. The objective of this study was to
      investigate the volatilisation reducing potential of formulation types and
      adjuvants, and to propose an effective vapour pressure for pesticide fate
      modelling. Several formulations of fenpropimorph, pyrimethanil and tebuconazole
      were produced and tested in a wind tunnel to evaluate the effect of formulation
      on active ingredient volatilisation. Produced emulsifiable concentrates with high
      volatile solvents did not offer any reduction in volatilisation, while the low
      volatile solvent reduced the volatilisation of pyrimethanil and fenpropimorph
      with 79.2 and 52.9%, respectively. The microemulsion reduced the volatilisation
      of fenpropimorph, pyrimethanil and tebuconazole with 57.6, 57.8 and 49.8%,
      respectively. High surfactant-active ingredient ratios (100:1) reduced the
      volatilisation of applied amount of pyrimethanil with 50%, on average. The
      effective vapour pressure of pyrimethanil formulated as a commercial available
      suspension concentrate was reduced by 33.8%. The commercial available
      emulsifiable concentrate did not reduce volatilisation of fenpropimorph.
      Effective vapour pressures of formulated fenpropimorph and pyrimethanil were
      determined and showed a high correlation with the amount volatilised within 48h.
      The saturated vapour pressure is useful when comparing the volatility of active
      ingredients, but effective vapour pressures are more appropriate to be used in
      pesticide fate models.

PMID- 29602112
TI  - Long-term monitoring programme of polychlorinated dioxins and polychlorinated
      furans in ambient air of Catalonia, Spain (1994-2015).
AB  - Reductions in concentrations of persistent organic pollutants were observed for
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in a comparison of
      two consecutive decades ending in December 31, 2015 (n = 413) and compiled from a
      48-station long-term air-monitoring network in Catalonia, Spain. Reductions were
      observed in geometric mean concentration of total PCDD/Fs, decreasing at a rate
      of 11% yr-1. Results reflect the relative success of improved pollution control
      measures at industry and traffic locations. At traffic and industrial locations,
      PCDD/Fs were reduced by around 68% (from 70 to 22 fg I-TEQ/m3) and 66% (from 57
      to 19 fg I-TEQ/m3), respectively. The highest concentration of 1196 fg I-TEQ/m3
      was observed during the first decade at an industrial location. The highest
      concentration over the second decade was at a background location during winter
      (674 fg I-TEQ/m3). Winter observations are generally higher than those recorded
      in summer, as evident in an 8-year period of moderate PCDD/F levels (<250 fg I
      TEQ/m3, n = 143). PCDD/F congener profiles were identified has having less
      chlorinated PCDD/F, indicating the presence of nearby combustion sources at
      selected locations. More long-term sampling campaigns, combined with network
      optimization and integration into a meteorological model, can offer a tool for
      future PCDD/Fs control measures in not only Catalonia - but also applicable to
      other areas.

PMID- 29602113
TI  - A novel partial-denitrification strategy for post-anammox to effectively remove
      nitrogen from landfill leachate.
AB  - Anaerobic ammonia oxidation (anammox) has shown great promise for nitrogen
      removal in low C/N wastewater such as landfill leachate. However, 11% of NO3--N
      is stoichiometrically produced, which decreases the total nitrogen (TN) removal
      efficiency. In this study, a strategy for post anammox was developed to
      effectively remove TN from leachate. A tandem conversion of NO3--N to NO2--N
      (partial denitrification) was accomplished by supplying substrate for subsequent
      anammox, by supplementing the electron donor deficient condition. This process
      greatly improved NH4+-N and TN removal from leachate, reaching a 95% efficiency.
      Quantitative real-time polymerase chain reaction results showed that a high
      abundance of anammox bacteria, with a titer of 109 copy numbers/L, was enriched,
      accounting for 9.66% of the total bacterial community, and indicating the success
      of this novel strategy for the TN removal in leachate.

PMID- 29602114
TI  - Land subsidence in the Friuli Venezia Giulia coastal plain, Italy: 1992-2010
      results from SAR-based interferometry.
AB  - Land subsidence is a concern in many coastal plains worldwide, particularly in
      the low-lying areas already facing sea level rise due to climate change, and much
      still needs to be done, with respect to both mapping land subsidence and gaining
      a comprehensive understanding of the relevant cause-effect relationships. Land
      subsidence of the northern coastal plain encompassing the Friuli Venezia Giulia
      (FVG) region in Italy, remains, to the authors' knowledge, poorly investigated.
      This coastland includes low-lying agricultural and urban areas and highly
      valuable lagoon environments, archaeological and touristic sites, and industrial
      zones. Here, we resolve land subsidence in the coastal plain between the
      Tagliamento River delta and the Isonzo River mouth over the period 1992-2010
      using Envisat ASAR and ERS1/2 interferometric datasets. We identify a large
      variability of the land subsidence and a spatial gradient that ranges from less
      than 1mm/year in the high southwestern plain toward the littoral to more than
      5mm/year close to the Tagliamento River delta. A comparison between the 2003-2010
      and 1992-2000 sinking rates depicts quite similar behaviors of the process over
      the two time spans. The analysis indicates unclear correlations between ground
      movements and the typical driving mechanisms acting in the north Adriatic coastal
      plains, such as the variability of the morphological setting, the subsoil
      characteristics and the land use. We reason that multi-component mechanisms
      contribute to the observed image of the subsidence in the FVG coastland.
      Specifically, anthropogenic activities, e.g., groundwater exploitations,
      hydraulic reclamations and the development of newly built-up areas, are
      superposed to natural mechanisms related to the spatial variability of the
      subsoil characteristics, typical of transitional coastal environments.

PMID- 29602115
TI  - Decreased waterborne pathogenic bacteria in an urban aquifer related to intense
      shallow geothermal exploitation.
AB  - The implications of intensive use of shallow geothermal energy resources in
      shallow urban aquifers are still not known for waterborne pathogens relevant to
      human health. Firstly, we hypothesized that waterborne enteric pathogens would be
      relatively increased in heated groundwater plumes. To prove this, microbiological
      sampling of 31 piezometers covering the domain of an urban groundwater body
      affected by microbiological contamination and energetically exploited by 70
      groundwater heat pump systems was performed. Mean differences of pathogenic
      bacteria contents between impacted and non-impacted monitoring points were
      assessed with a two-tailed independent Student's t-test or Mann-Whitney U and
      correlation coefficients were also calculated. Surprisingly, the results obtained
      revealed a significant and generalized decrease in waterborne pathogen contents
      in thermally impacted piezometers compared to that of non-impacted piezometers.
      This decrease is hypothesized to be caused by a heat shock to bacteria within the
      heat exchangers. The statistically significant negative correlations obtained
      between waterborne pathogen counts and temperature could be explained by the
      spatial distribution of the bacteria, finding that bacteria start to recover with
      increasing distance from the injection point. Also, different behavior groups
      fitting exponential regression models were found for the bacteria species
      studied, justified by the different presence and influence of several aquifer
      parameters and major, minor and trace elements studied, as well as the
      coexistence with other bacteria species. The results obtained from this work
      reinforce the concept of shallow geothermal resources as a clean energy source,
      as they could also provide the basis to control the pathogenic bacteria contents
      in groundwater bodies.